PMID- 26831871 TI - Coronary leukocyte activation in relation to progression of coronary artery disease. AB - Leukocyte activation has been linked to atherogenesis, but there is little in vivo evidence for its role in the progression of atherosclerosis. We evaluated the predictive value for progression of coronary artery disease (CAD) of leukocyte activation markers in the coronary circulation. Monocyte and neutrophil CD11b, neutrophil CD66b expression and intracellular neutrophil myeloperoxidase (MPO) in the coronary arteries were determined by flow cytometry in patients undergoing coronary angiography. The primary outcome included fatal and nonfatal myocardial infarction or arterial vascular intervention due to unstable angina pectoris. In total 99 subjects who were included, 70 had CAD at inclusion (26 patients had single-vessel disease, 18 patients had twovessel disease and 26 patients had three-vessel disease). The median follow-up duration was 2242 days (interquartile range: 2142-2358). During follow-up, 13 patients (13%) developed progression of CAD. Monocyte CD11b, neutrophil CD11b and CD66b expression and intracellular MPO measured in blood obtained from the coronary arteries were not associated with the progression of CAD. These data indicate that coronary monocyte CD11b, neutrophil CD11b and CD66b expression and intracellular MPO do not predict the risk of progression of CAD. PMID- 26831872 TI - Determining optimal diagnostic criteria through chronicity and comorbidity. AB - PURPOSE: Contemporary approaches to clinical diagnosis have not adequately exploited state-of-the-art empirical techniques in deriving diagnostic criterion sets that are statistically optimal based on 1) relevant external indicators and 2) replicability across data sets. We provide a proof of concept that optimal criterion sets can be derived with respect to alcohol use disorder (AUD) diagnosis that are both more efficient and precise than current systems. METHODS: Using data from the National Epidemiologic Survey on Alcohol and Related Conditions we selected chronicity (i.e. persistence) of AUD diagnosis and comorbidity of AUD with other disorders as validation criteria on which to optimize the size of the AUD criterion set and the threshold for AUD diagnosis. We used cross-validation and consensus approaches for choosing a final solution. RESULTS: Cross-validation did not produce a solution that replicated across random subsamples or differed from conventional diagnosis. Alternatively, consensus produced a more global solution that was associated with greater validity than "conventional" diagnosis. CONCLUSION: Such methods, if applied to extant diagnostic criteria and algorithms can generate simpler and more reliable rules and hold promise for greatly reducing misclassification of individuals in both research and applied clinical contexts. PMID- 26831873 TI - Frequency dependence 3.0: an attempt at codifying the evolutionary ecology perspective. AB - The fitness concept and perforce the definition of frequency independent fitnesses from population genetics is closely tied to discrete time population models with non-overlapping generations. Evolutionary ecologists generally focus on trait evolution through repeated mutant substitutions in populations with complicated life histories. This goes with using the per capita invasion speed of mutants as their fitness. In this paper we develop a concept of frequency independence that attempts to capture the practical use of the term by ecologists, which although inspired by population genetics rarely fits its strict definition. We propose to call the invasion fitnesses of an eco-evolutionary model frequency independent when the phenotypes can be ranked by competitive strength, measured by who can invade whom. This is equivalent to the absence of weak priority effects, protected dimorphisms and rock-scissor-paper configurations. Our concept differs from that of Heino et al. (TREE 13:367-370, 1998) in that it is based only on the signs of the invasion fitnesses, whereas Heino et al. based their definitions on the structure of the feedback environment, summarising the effect of all direct and indirect interactions between individuals on fitness. As it turns out, according to our new definition an eco-evolutionary model has frequency independent fitnesses if and only if the effect of the feedback environment on the fitness signs can be summarised by a single scalar with monotonic effect. This may be compared with Heino et al.'s concept of trivial frequency dependence defined by the environmental feedback influencing fitness, and not just its sign, in a scalar manner, without any monotonicity restriction. As it turns out, absence of the latter restriction leaves room for rock-scissor-paper configurations. Since in 'realistic' (as opposed to toy) models frequency independence is exceedingly rare, we also define a concept of weak frequency dependence, which can be interpreted intuitively as almost frequency independence, and analyse in which sense and to what extent the restrictions on the potential model outcomes of the frequency independent case stay intact for models with weak frequency dependence. PMID- 26831874 TI - [Present status of preoperative staging and contemplation on preoperative precision staging for gastric cancer]. AB - The aim of the preoperative staging of gastric cancer was to evaluate the depth of tumor infiltration (T-stage), the extent or number of metastasized lymph nodes (N-stage), and distant metastasis (M-stage) before surgery, to develop an optimal therapeutic scheme for the patients with gastric cancer. Traditional methods of preoperative staging for gastric cancer are usually imaging diagnostic techniques, such as endoscopic ultrasonography (EUS), CT scan, magnetic resonance imaging (MRI) and laparoscopic exploration. At present, the accuracy of preoperative TNM staging of gastric cancer can generally reach 70% to 85% with significant clinical benefit. The accurate preoperative staging for cancer patients can have a major role in determining the final clinical outcome and in predicting the prognosis. According to the concept of "precision medicine", to achieve "preoperative precision staging of gastric cancer", the application of imaging diagnostic techniques must be combined with the analysis of individual genetic information or tumor molecular pathological classification, which should be based on research of the disease genomics, proteomics and metabolomics. In this article, we provide a review of results on preoperative staging of gastric cancer in recent years, and we also discuss how to think about the "preoperative precision staging of gastric cancer", with special emphasis on the potential of molecular imaging techniques, circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA), molecular targets for tumor targeting therapy and molecular pathological classification, etc. in judging bio-molecular behavior of gastric cancer before surgery. PMID- 26831875 TI - [Role and management of cancer clinical database in the application of gastric cancer precision medicine]. AB - Precision medicine is a new medical concept and medical model, which is based on personalized medicine, rapid progress of genome sequencing technology and cross application of biological information and big data science. Precision medicine improves the diagnosis and treatment of gastric cancer to provide more convenience through more profound analyses of characteristics, pathogenesis and other core issues in gastric cancer. Cancer clinical database is important to promote the development of precision medicine. Therefore, it is necessary to pay close attention to the construction and management of the database. The clinical database of Sun Yat-sen University Cancer Center is composed of medical record database, blood specimen bank, tissue bank and medical imaging database. In order to ensure the good quality of the database, the design and management of the database should follow the strict standard operation procedure(SOP) model. Data sharing is an important way to improve medical research in the era of medical big data. The construction and management of clinical database must also be strengthened and innovated. PMID- 26831876 TI - [Precision lymphadenectomy for locally advanced gastric cancer]. AB - Based upon studies from randomized clinical trials, the extended (D2) lymph node dissection is now recommended as a standard procedure for local advanced gastric cancer worldwide. However, the rational extent lymphadenectomy for local advanced gastric cancer has remained a topic of debate in the past decades. Patients with more lymph nodes harvested may have better survival. Negative node count may provide prognostic information for gastric cancer patients. The extranodal metastasis is significantly associated with the survival of gastric cancer patients and should be incorporated into N stage. In total gastrectomy for proximal gastric cancer without great curvature invasion, prophylactic splenectomy should be avoided not only for operative safety but also for survival benefit. The metastatic rate of No14v nodes for patients with distal stage III( disease is about 20%, so D2+ No.14v lymphadenectomy may be an option in a potentially curative gastrectomy for tumors with metastasis to the No.6 nodes. According to JCOG9501, extend D2+PAND should not be used to treat curable stage T2b, T3, N1-2 (II(B-III(A) gastric cancer. But the clinical benefit of D2+PAND for patients with stage T4 and/or stage N3 (III(B, III(C) disease could not be determined. The quality control of D2 procedure is very important for the prognosis of gastric cancer patients. Base on the experience from Europe, Unite States and China, centralization of gastric cancer treatment will improve the outcome of gastric cancer operation effectively. PMID- 26831877 TI - [Individualized treatment strategies for gastric cancer based on D2 dissection]. AB - The Standard for Diagnosis and Treatment of Gastric Cancer published by China Ministry of Health in 2011 clearly advocates that individualized treatment strategy based on D2 standard radical surgery should be recommended, which is according to staging and biologic typing. The present review will comment on the strategy from the following aspects: clinical TNM staging, pathological TNM staging, biologic typing, occult lymph node metastasis and molecular typing. PMID- 26831878 TI - [Advantages and disadvantages of three-dimensional technique in laparoscopic gastrectomy for gastric cancer]. AB - Recently, the technological advancements have led to the introduction of new three-dimension (3D) laparoscopic system. 3D technique in laparoscopic radical gastrectomy provides an abdominal strong stereoscopic depth and accurate operative field, and can be helpful for the beginner to shorten the learning curve. Moreover, spatial orientation becomes more accurate with 3D technique. 3D technique also has the advantages of clearer anatomical level, better vessel exposure, lymph node dissection and digestive tract reconstruction. However, there are still some defects of 3D laparoscopic system. For example, the surgeon may not adapt to 3D vision at the beginning, and special equipment is required to display the data. PMID- 26831879 TI - [Important international and Chinese clinical trials on gastric cancer]. AB - In the era of evidence-based medicine, the diagnosis and treatment of gastric cancer are based on the evidence from important clinical trials. International and Chinese trials are performed on early, locally advanced, and late stage gastric cancer and the key points of trials of each aspect are different. Clinical trials of early gastric cancer mainly focus on the minimally invasive treatments like endoscopic resection and laparoscopic surgery. Clinical trials of locally advanced gastric cancer aim to raise the extent of radical treatment and multimodality treatment patterns. As to late stage gastric cancer, the trials aiming to prolong survival of the patients, conversion treatment, target therapy, immune therapy and new drug development are mostly interested. PMID- 26831880 TI - [Re-discussion of lymph node metastasis from gastric cancer on prognostic evaluation]. AB - Lymph node metastasis from gastric cancer is one of the most important events in the progress of disease, which may reflect the disease situation and contribute to evaluate accurately prognosis. Although the detailed mechanism of lymph node metastasis from gastric cancer has not been clearly elucidated, nodal metastasis comprise of a series of events involving the alterations of tumor biological characteristics, including changes of cancer cell proliferation, invasion, chemotaxis, and pathway of lymphatic drainage. As we know, assessment of lymph node metastatic status is significantly associated with both therapeutic strategy and prognostic prediction, It is controversial to adopt the optimal category of lymph node metastasis in clinical practice. Category based on the number of lymph node metastasis (e.g. N stage of UICC TNM classification) is considered as a prominent variable to apply for gastric cancer worldwide, nevertheless, category based on extent of lymph node metastasis (e.g. N stage of JGCA classification) is capable of contributing to the appropriate surgical procedure for patients. It has not reached a consensus for the assessment impacts of several special variables on prognostic evaluation in gastric cancer, including nodal micrometastasis, isolated tumor cells (ITCs) in lymph nodes, and skipping metastasis of lymph nodes, which needs further investigations to determining the application values in gastric cancer. PMID- 26831881 TI - [Controversy and confusion in preoperative imaging precise staging of gastric cancer]. AB - AJCC determined the pathological standards for staging of gastric cancer, but no corresponding radiological signs of a single stage were described or documented. The vacancy of authority standards and limitation of the existing radiological modalities has caused the "stage fright" of the radiologists during the clinical practices. The controversy and confusion under different cognitive aspects can be summarized as follows: (1) If the gastric submucosal layer is not detected, it can only take the indirect standard of "50% thickness ratio" to distinguish T1 and T2. (2) T2 tumors may be overstaged as T3, as a result of the undetectable thin subserosa layer. (3) T3 tumors may be overstaged as T4, because of the inflammatory and fibrosis strands and spiculations near the serosa, and the existence of the gastric bare area. (4) The diagnostic imaging criteria for T4b are still controversial, and the opinions are not uniform about the resectable signs. Some significantly infiltrated unresectable tumors lack typical radiology signs. (5) Size is still the widely-used direct criterion for the diagnosis of lymph node metastasis, however the accuracy of N staging is only 50%-70%. (6) It lacks the typical sign for the diagnosis of early peritoneal metastasis, with a diagnostic sensitivity of only 50%. There is no fundamental breakthrough for the existing imaging modalities to solve the above controversies on the preoperative precise staging. However, the situations can be improved by standardization of the examination and reporting process (oral filling, multi-phase enhancement, multi planar reconstruction, and window width/level technique, etc.), the exploration of the fine signs(hyperattenuating serosa sign, smudge sign, etc.) and the exploration of new modalities (spectral CT, diffusion weighted MR imaging, etc.). PMID- 26831882 TI - [Integration and analysis of associated data in surgical treatment of gastric cancer based on multicenter, high volume databases]. AB - OBJECTIVE: To elucidate the current diagnosis and treatment status of gastric cancer in the Chinese population based on three high volume databases. METHODS: Clinical and pathological data of patients who underwent gastric cancer resection with complete follow-up information between January 2000 and December 2012 from Sun Yat-sen University Cancer Center, The First Affiliated Hospital of China Medical University and Tianjin Medical University Cancer Hospital were retrospectively analyzed. The overall survival rate was calculated by Kaplan Meier method. The prognostic risk factors were analyzed by using Cox proportional hazards model. RESULTS: A total of 8 338 cases were enrolled into the study, including 2 977 cases (35.7%) from Sun Yat-sen University Cancer Center, 3 043 cases (36.5%) from The First Affiliated Hospital of China Medical University and 2 318 cases (27.8%) from Tianjin Medical University Cancer Hospital. There were 5 852 male cases and 2 486 female cases with a ratio of 2.4 to 1.0. The age of patients was from 15 to 89 years old (median 59 years old). The ratio of early gastric cancer (T1NanyM0) was 11.5% (956/8 338). There were 2 226 gastric cancer cases (26.7%) originating from the fundus and cardiac region, 1 637 cases (19.6%) from the body, 3739 (44.9%) cases from the antrum, and 736 cases (8.8%) from the whole stomach. The median maximal tumor diameter was (4.5 +/- 2.8) cm. Based on the Lauren classification, 3 448 cases (41.4%) were intestinal type and 4 890 cases (58.6%) diffuse type. A total of 1 975 cases (23.7%) and 6 363 cases (76.3%) underwent complete and subtotal gastrectomy respectively. The majority of patients (7 707 cases, 92.4%) underwent radical gastric resection, while 631 cases (7.6%) palliative resection. According to AJCC/UICC seventh edition of gastric cancer TNM staging system, 802 patients (9.6%) were stage I(A, 735 patients (8.8%) stage I(B, 695 patients (8.3%) stage II(A, 1 507 patients (18.1%) stage II(B, 1 247 patients (15.0%) stage III(A, 1 342 patients (16.1%) stage III(B, 1 583 patients (19.0%) stage III (C and 427 patients (5.1%) stage IIII(. The average number of retrieved lymph node was 21.0 +/- 13.1, in which 5 761 patients (69.1%) had more than 15 retrieved lymph nodes. The overall 1-, 3-, 5- and 10-year survival rates were 83.0%, 56.8%, 49.1% and 43.0% respectively. For patients receiving radical resection, the 1-, 3-, 5- and 10-year survival rates were 84.9%, 59.5%, 51.7% and 45.3% respectively. The overall 5-year survival rates for different stages were as follows: stage I(A 93.8%, stage I(B 80.8%, stage II(A 70.8%, stage II(B 59.6%, stage III(A 44.4%, stage III(B 32.9%, stage III(C 18.9% and stage IIII( 10.2%. Cox regression model showed that age, tumor site, tumor size, Lauren type, T staging, N staging, M staging and number of retrieved lymph nodes were independent factors affecting the prognosis of gastric cancer patients (P=0.000). CONCLUSION: Retrospective study on these domestic three high volume databases demonstrates the clinical and pathological characteristics of gastric cancer based on Chinese population, which is expected to stand as a ground of basic data for future clinical research. PMID- 26831883 TI - [Analysis of risk factors for No.11p lymph node metastasis in advanced gastric cancer]. AB - OBJECTIVE: To investigate the risk factors for No.11p lymph node metastasis in advanced gastric cancer. METHODS: A retrospective analysis was executed of the clinical data of 204 patients who were subject to advanced gastric cancer and accepted radical gastrectomy in Tianjin Cancer Hospital from January 2007 to December of 2011. All of the patients were diagnosed as gastric adenocarcinoma and received No.11p lymph node dissection. The general information of the patients and the number of dissected and positive lymph nodes were recorded in detail. Univariate and multivariate analysis of clinicopathological factors influencing No.11p lymph metastasis were performed by chi-square test and binary Logistiic Discussion, respectively. RESULTS: The No.11p lymph node metastasis rate is 14.3%(29/204) in the 204 patients. The univariate analysis showed that No.11p lymph metastasis was correlated with diameter of tumor, depth of invasion (T stage), lymph node metastasis (N stage) and TNM stage (chi(2)=5.106, chi(2)=5.368, chi(2)=25.911, P<0.05). The association between the metastasis of the regional lymph nodes No.1, No. 3, No. 4sb, No. 5, No. 7, No. 9 and No.11p was significant (chi(2)=4.228, chi(2)=10.655, chi(2)=17.954, chi(2)=11.087, chi(2)=15.142, chi(2)=16.727, all P<0.05). Multivariate analysis confirmed that lymph node N3 stage(OR=4.791, 95% CI:2.056-11.167), No.4sb(OR=3.498, 95% CI:1.157 10.578) and No.9(OR=4.006, 95% CI:1.359-11.805) were three independent risk factors of No.11p lymph node metastasis(all P<0.05). CONCLUSION: The No.11p lymph node dissection in radical gastrectomy conventionally is reasonable and necessary. Lymph node N3 stage and the metastasis of regional lymph No.4sb and No.9 are independent risk factors of the metastasis of No.11p lymph node. PMID- 26831884 TI - [Application of laparoscopic function-preservation proximal gastrectomy in the treatment of early gastric cancer]. AB - OBJECTIVE: To discuss the safety and feasibility in the preservation to hepatic branch of vagus nerve by the side-to-side tubular gastroesophageal anastomosis within the laparoscopic radical proximal gastrectomy for early gastric cancer(EGC). METHODS: Retrospective analysis on the intraoperative and postoperative data of 7 EGC patients receiving laparoscopic radical proximal gastrectomy from January 2014 to January 2015 was carried out. All the patients underwent the preservation of hepatic branch of the vagus nerve by side-to-side tubular gastroesophagreal anastomosis. RESULTS: All the 7 patients completed operations successfully without conversion to open surgery. The mean operative time was (213.1 +/- 22.1) minute, the mean reconstruction time was (56.9 +/- 11.6) minute, and the mean blood loss was (38.6 +/- 28.1) ml. Postoperative time to flatus was (2.4 +/- 0.5) day, and postoperative hospital stay was (9.3 +/- 0.9) day. No operation-related complications were observed. No severe malnutrition, no recurrence or death, and no severe esophageal reflux during follow-up period were found. CONCLUSION: The preservation of hepatic branch of the vagus nerve by side-to-side tubular gastroesophagreal anastomosis within laparoscopic radical proximal gastrectomy for ECG is safe and feasible. PMID- 26831885 TI - [Survival rate of proximal and total gastrectomy in treatment of esophagogastric junction adenocarcinoma (Siewert II( Types)]. AB - OBJECTIVE: To compare the survival rate of proximal gastrectomy and total gastrectomy in the treatment of esophagogastric junction (EGJ) adenocarcinoma (Siewert II( types), and to provide reference for clinical choice. METHODS: A total of 533 patients with Siewet II( type EGJ adenocarcinoma were screened. All the patients underwent radical operations and were pathologically diagnosed as Siewet II( type EGJ adenocarcinoma in Xijing Hospital of Digestive Diseases from May 2008 to March 2014. These patients all had complete followed-up data. Finally, 234 patients were enrolled into the retrospective study, and divided into proximal gastrectomy group(117 patients) and total gastrectomy group (117 patients) based on the matching of age, sex, tumor size, TNM staging, and differentiation. The survival rate was compared between the two groups. RESULTS: In proximal gastrectomy and total gastrectomy group, the overall 3-year survival rate was 65.6% and 62.6% respectively, and the overall 5-year survival rate was 53.8% and 44.5% respectively. No significant difference was found between the two groups (P=0.768). In subgroup analyses of 3-year survival rate between proximal gastrectomy group and total gastrectomy group, the results were as follows: 72.8% and 80.4% respectively (P=0.423) for tumor diameter <=4 cm, 57.9% and 46.5% (P=0.239) for tumor diameter >4 cm, 83.3% and 83.3% (P=0.998) for high differentiated EGJ adenocarcinoma, 68.2% and 53.3% (P=0.270) for moderate differentiated EGJ adenocarcinoma, 56.1% and 69.6% (P=0.280) for poorly differentiated EGJ adenocarcinoma, 64.8% and 56.0% (P=0.451) for mucinous EGJ adenocarcinoma, 80.0% and 76.9% (P=0.912) for T1-2 stage EGJ adenocarcinoma, 64.3% and 60.4% (P=0.610) for T3 stage, 50.0% and 62.5% (P=0.953) for T4a stage, 92.3% and 100% (P=0.380) for stage I( EGJ adenocarcinoma, 79.6% and 66.3%(P=0.172) for stage II(, 42.6% and 49.5% (P=0.626) for stage I I(. All above differences between the two groups were not significant(all P>0.05). CONCLUSION: Proximal gastrectomy and total gastrectomy are comparable in terms of 3-year and 5-year survival rates. PMID- 26831886 TI - [Efficacy comparison of lymph node dissection patterns of the reverse and the cabbage in hand-assisted laparoscopic D2 radical gastrectomy]. AB - OBJECTIVE: To compare the clinical efficacy of the lymph node dissection patterns of the reverse and the traditional cabbage in hand-assisted laparoscopic D2 radical gastrectomy (HALG). METHODS: From December 2010 to October 2013, 194 patients with HALG in Chengdu Military General Hospital were enrolled in this study. According to the pattern of lymph node dissection, 108 patients were performed with the reverse procedure which took spleen as starting point, from left to right, and 86 patients were performed with the traditional cabbage procedure which took the abdominal cavity as the center, from both sides to middle. A retrospective comparative analysis was made on the intra- and post operative data between the two groups. RESULTS: All the patients were successfully performed with HALG, and no peri-operative death occurred. There were no significant differences in the incision length [(7.0 +/- 0.2) cm vs. (6.9 +/- 0.3) cm], the operative time [(170.9 +/- 33.8) minute vs. (174.6 +/- 22.4) minute], dissected lymph node number (17.6 +/- 7.5 vs. 17.1 +/- 5.8) and post operative complications [(6.5%(7/108) vs. 8.1%(7/86)] between the reverse group and cabbage group (all P>0.05). However, less blood loss [(204.6 +/- 98.2) ml vs. (259.1 +/- 122.6) ml, P<0.01] and shorter postoperative hospital stay [(9.0 +/- 1.7) day vs. (10.5 +/- 4.0) day, P<0.01] were observed in reverse group as compared to cabbage group. During 1 to 6 months follow-up, no death case was found in reverse group, while 1 case died due to upper gastrointestinal bleeding 48 days after operation in cabbage group. CONCLUSION: Efficacy is similar between the two HALG procedures in lymph node dissection, while reverse procedure has certain advantages, such as less blood loss and faster recovery. PMID- 26831887 TI - [Associations of apparent diffusion coefficient value from MR diffusion-weighted imaging with Ki-67 expression and differentiation grade in gastric cancer]. AB - OBJECTIVE: To examine the associations of apparent diffusion coefficient (ADC) value from MR diffusion-weighted imaging (DWI) with Ki-67 expression and differentiation grade in gastric cancer. METHODS: Images and pathologic data of 68 gastric cancer patients between September 2013 and February 2015 in Affiliated Changshu Hospital of Soochow University were analyzed retrospectively. The expression of Ki-67 antigen in cancer tissue sample was determined by immunohistochemistry. Ki-67 labeling index(LI) was calculated to divide the cases into low Ki-67 group(Ki-67 LI <50%) and high Ki-67 group (Ki-67 LI >= 50%). Associations of ADC value with differentiation grade and Ki-67 LI were examined. RESULTS: Mean ADC value of low Ki-67 LI group was significantly higher than that of high Ki-67 LI group [(0.977 +/- 0.100) * 10(-3) mm(2)/s vs. (0.859 +/- 0.064) * 10(-3) mm(2)/s, P=0.000]. The ADC value was negatively correlated with Ki-67 LI (r=-0.685, P=0.000). Mean ADC value of well differentiated adenocarcinoma, moderately differentiated adenocarcinoma, poorly differentiated adenocarcinoma, and signet-ring cell carcinoma was (1.124 +/- 0.080) * 10(-3) mm(2)/s, (0.950 +/- 0.064) * 10(-3) mm(2)/s, (0.899 +/- 0.091) * 10(-3) mm(2)/s, and (0.894 +/- 0.081) * 10(-3) mm(2)/s respectively. Difference of ADC value among differentiation grades was significantly different (F=11.405, P=0.000). Difference of ADC value between well differentiated adenocarcinoma and non-well differentiated adenocarcinoma was significantly different(P=0.000). CONCLUSION: ADC value is associated with differentiation grade and Ki-67 LI of gastric cancer, which may be used as a noninvasive predictor for evaluating the proliferation and differentiation grade of gastric cancer. PMID- 26831888 TI - [Effect of synergistic polarization macrophage modulated by N-terminal domain of a2 vacuolar ATPase and macrophage colony stimulating factor on proliferation of gastric cancer cells]. AB - OBJECTIVE: To investigate the synergistic effect between the N-terminus domain of the a2 isoform of vacuolar ATPase (a2NTD) and macrophage colony-stimulating factor (M-CSF) on modulating macrophage polarization and the impact of polarized macrophages on proliferation of gastric cancer cells. METHODS: Peripheral blood mononuclear cells were derived from healthy donor and induced into macrophages. Then macrophages were randomly divided into four groups: the control group (RPMI 1640), the experimental group I (M-CSF 100 MUg/L), the experimental group II (a2NTD 500 MUg/L) and the experimental group III (a2NTD 500 MUg/L plus M-CSF 100 MUg/L). After stimulation for 48 hours, double color immunofluorescence cytochemistry was adopted to detect the expression of cell membrane molecules on macrophages; ELISA was used to measure the secretion of cytokines IL-10 and IL 12; CCK-8 assay was used to evaluate the impact of macrophages on proliferation ability of gastric cancer cell strain SGC-7901. RESULTS: The expression of CD68, also known as macrophage surface antigen, was detected on macrophage membrane in all four groups (+). The mean absorbance (A) was 0.092 +/- 0.005 in control group, 0.095 +/- 0.006 in group I, 0.094 +/- 0.005 in group II, 0.094 +/- 0.005 in group III, and no significant differences were observed among 4 groups (all P>0.05). Meanwhile, the expression of CD206, which mainly exists on M2 macrophage membrane, was hard to detect in control group (-) with A 0.025 +/- 0.004; it was normal in groupI and group II (+) with A 0.191 +/- 0.012 in group I and 0.197 +/- 0.136 in group II (P=0.212), and it was up-regulated significantly in group III (+++) with A 0.285 +/- 0.011. There were significant differences between either two groups except group I and group II (all P<0.01). Secretion of IL-10 in group I and group II [(85.65 +/- 13.64) ng/L and (87.77 +/- 14.25) ng/L] was significantly higher compared with control group [(71.67 +/- 7.56) ng/L, P<0.01]. Secretion of IL-12 in group I and group II [(9.91 +/- 1.50) ng/L and (10.15 +/- 1.80) ng/L] was significantly lower compared with control group [(16.87 +/- 1.10) ng/L, P<0.01]. Secretion of IL-10 in group III [(116.98 +/- 14.27) ng/L] was the highest, and secretion of IL-12 [(5.31 +/- 0.88) ng/L] was the lowest (all P<0.01). There was a synergistic effect between a2NTD and M-CSF on the secretion of both IL-10 and IL-12. Elevated proliferation of gastric cancer cell strain SGC 7901 was detected in all four groups, in which group III showed the greatest impact compared with other 3 groups (P<0.01). CONCLUSIONS: a2NTD and M-CSF show a synergistic effect in modulating macrophage phenotype and the secretion of IL-10 and IL-12. The polarized macrophage can significantly enhance proliferation of gastric cancer cell strain SGC-7901. PMID- 26831889 TI - [Progression of immunotherapy in gastric cancer]. AB - Gastric cancer is a malignant disease with high incidence and mortality. The therapeutic methods for advanced gastric cancer, including chemotherapy and targeted therapy are very limited. Immunotherapy is a new method for cancer treatment. The immune checkpoint inhibitors developed for cancer treatment mainly target the CTLA-4 and PD-1/PD-L pathways. There have already been several inhibitors approved for the treatment of melanoma and non-small cell lung cancer by the FDA, including Ipilimumab (fully human antibody against CTLA-4), Pembrolizumab (fully human antibody against PD-1) and Nivolumab (fully human antibody against PD-1). There are also many on-going clinical trials investigating the value of immune checkpoint inhibitors in treating various malignancies, including advanced gastric cancer. In KEYNOTE-012 trial, for advanced gastric and esophagogastric junction cancer anti-PD-1 therapy seemed to be safe and effective for advanced gastric cancer with PD-L1 positivity. Moreover, studies of adoptive cell therapy and tumor vaccine in gastric cancer are underway. Here the latest developments in immunotherapy for gastric cancer will be illustrated. PMID- 26831890 TI - [Function preserving gastrectomy]. AB - Under the premise of radical resection in the treatment, it is of great significance to preserve partial gastric function so that the early gastric cancer (EGC) patients' postoperative quality of life (QOL) can be improved. In the patients with EGC in the upper third of the stomach, the emphasis is on the prevention of reflux esophagitis caused by bile and gastric juice reflux. Pylorus preserving gastrectomy (PPG) is applicable to the patients with EGC in the middle third of the stomach. In the patients with EGC in the lower third of the stomach, distal gastrectomy (DG) is performed in general. Various anastomosis ways are applied to reduce the negative impact of pylorus resection after DG. Furthermore, it should also be considered that reasonable vagal nerves preservation and lymph node dissection are both important for function preserving gastrectomy of EGC. Rational use of laparoscopy-assisted gastrectomy has advantages of lower invasiveness, faster recovery, etc. And the amplification effect of laparoscope can contribute to preserving nerves and gastric function. PMID- 26831891 TI - [Pylorus-preserving gastrectomy in treating middle-third early gastric cancer]. AB - Compared with distal gastrectomy, pylorus-preserving gastrectomy is less invasive which can decrease incidence of dumping syndrome, diarrhea and body weight lost, cholecystitis and gallstone, reflux gastritis and esophagitis and remnant gastric cancer. Based on new Japanese Gastric Cancer Treatment Guideline and new progression in the world, we give a review mainly basic characteristics, indications, operation details and short- and long-time outcomes after pylorus preserving gastrectomy. PMID- 26831892 TI - A randomised controlled trial of a Mediterranean Dietary Intervention for Adults with Non Alcoholic Fatty Liver Disease (MEDINA): study protocol. AB - BACKGROUND: Non-alcoholic fatty liver disease, the most prevalent liver disease in developed countries, remains difficult to manage with no proven safe and effective pharmacotherapy available. While weight reduction is the most commonly practiced treatment strategy, this is difficult to both achieve and/or maintain in the majority. Furthermore evidence-based dietary recommendations to guide the nutritional management of these patients are lacking. Using a randomised controlled trial design, this study compares the effectiveness of the Mediterranean diet to a standard low fat diet in terms of differences in insulin sensitivity, hepatic steatosis and metabolic outcomes in participants with non alcoholic fatty liver disease. METHODS: Ninety four eligible patients who have non-alcoholic fatty liver disease and who are insulin resistant, will be randomised into either a Mediterranean or low fat diet group for a 3 month intervention period. Insulin sensitivity will be measured on peripheral blood using Homeostatic Model Assessment and liver fat content quantified using Magnetic Resonance Spectroscopy. Both arms will consist of three face to face and three telephone call follow up consultations delivered by an Accredited Practicing Dietitian. The intervention arm focuses on recommendations from the traditional Mediterranean diet which have been tailored for use in the Australian population The standard arm uses the Australian Guide to Healthy Eating and the Australian National Heart Foundation dietary guidelines. Study recruitment will take place at four major metropolitan hospitals in Melbourne, Australia. Data collection will occur at all face to face reviews including baseline, 6, and 12 weeks. A follow up assessment to measure sustainability will take place at 6 and 12 months. The primary end point is improved insulin sensitivity scores at the 12 week time point. DISCUSSION: This trial aims to demonstrate in a large cohort of participants with NALFD that a Mediterranean diet independent of weight loss can result in significant benefits in liver fat and insulin sensitivity and that these changes are sustained at 12 months. These metabolic changes would potentially lead to reductions in the risk of chronic liver disease, heart disease, type 2 diabetes and liver cancer. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register ACTRN: ACTRN12615001010583 . PMID- 26831893 TI - Risk factors associated with the practice of child marriage among Roma girls in Serbia. AB - BACKGROUND: Relatively little research on the issue of child marriage has been conducted in European countries where the overall prevalence of child marriage is relatively low, but relatively high among marginalized ethnic sub-groups. The purpose of this study is to assess the risk factors associated with the practice of child marriage among females living in Roma settlements in Serbia and among the general population and to explore the inter-relationship between child marriage and school enrollment decisions. METHODS: The study is based on data from a nationally representative household survey in Serbia conducted in 2010 - and a separate survey of households living in Roma settlements in the same year. For each survey, we estimated a bivariate probit model of risk factors associated with being currently married and currently enrolled in school based on girls 15 to 17 years of age in the nationally representative and Roma settlements samples. RESULTS: The practice of child marriage among the Roma was found to be most common among girls who lived in poorer households, who had less education, and who lived in rural locations. The results of the bivariate probit analysis suggest that, among girls in the general population, decisions about child marriage school attendance are inter-dependent in that common unobserved factors were found to influence both decisions. However, among girls living in Roma settlements, there is only weak evidence of simultaneous decision making. CONCLUSION: The study finds evidence of the interdependence between marriage and school enrollment decisions among the general population and, to a lesser extent, among the Roma. Further research is needed on child marriage among the Roma and other marginalized sub-groups in Europe, and should be based on panel data, combined with qualitative data, to assess the role of community-level factors and the characteristics of households where girls grow up on child marriage and education decisions. PMID- 26831894 TI - Case report: Severe central nervous system manifestations associated with aberrant efavirenz metabolism in children: the role of CYP2B6 genetic variation. AB - BACKGROUND: Efavirenz, widely used as part of antiretroviral drug regimens in the treatment of paediatric human immunodeficiency virus infection, has central nervous system side effects. We describe four children presenting with serious, persistent central nervous system adverse events who were found to have elevated plasma efavirenz concentrations as a result of carrying CYP2B6 single nucleotide polymorphisms, known to play a role in the metabolism of EFV. None of the children had a CYP2B6 wildtype haplotype. We believe this is the first case of cerebellar dysfunction associated with efavirenz use to be described in children. CASE PRESENTATION: Four black African children, between the ages of 4 and 8 years presenting between 1 and 20 months post-efavirenz initiation, are described. Cerebellar dysfunction, generalised seizures and absence seizures were the range of presenting abnormalities. Plasma efavirenz levels ranged from 20-60 mg/L, 5-15 times the upper limit of the suggested reference range. All abnormal central nervous system manifestations abated after efavirenz discontinuation. CONCLUSION: Efavirenz toxicity should always be considered in human immunodeficiency virus infected children with unexplained central nervous system abnormalities. Our findings further our understanding of the impact of genetic variants on antiretroviral pharmacokinetics in children across various ethnic groups. Screening for potential EFV-toxicity based on the CYP2B6 c.516 SNP alone, may not be adequate. PMID- 26831895 TI - Microbial yield from physiotherapy assisted sputum production in respiratory outpatients. AB - BACKGROUND: Sputum is a key diagnostic sample for those with chronic chest conditions including chronic and allergic aspergillus-related disease, but often not obtained in clinic. The objective of this study was to evaluate physiotherapeutic interventions to obtain sputum from those not able to spontaneously produce and the subsequent microbiological result. METHODS: Sputum samples were collected by physiotherapists from patients attending routine outpatient clinics managing their aspergillus-related diseases who were unable to spontaneously produce. Active Cycle of Breathing Techniques (ACBT) technique was applied first, for 10 min, followed by hypertonic saline induction using a Pari LC plus or Pari Sprint nebuliser, if necessary and deemed safe to do so. Samples processed in the laboratory using standard microbiological techniques for bacterial and fungal culture with the addition of Aspergillus real-time PCR. RESULTS: Samples were procured from 353 of 364 (97%) patients, 231 (65%) by ACBT and 119 (34%) with administration of hypertonic saline. Three of 125 (2.4%) patients had significant bronchospasm during sputum induction. Sixteen patients' sputum tested positive for Aspergillus culture, contrasting with 82 whose Aspergillus PCR was positive, 59 with a strong signal. PCR improved detection of Aspergillus by 350%. Sputum from 124 (34%) patients cultured other potentially pathogenic organisms which justified specific therapy. CONCLUSIONS: Physiotherapeutic interventions safely and effectively procured sputum from patients unable to spontaneously produce. The method for sputum induction was well-tolerated and time-efficient, with important microbiological results. PMID- 26831896 TI - Neonatal and maternal outcomes following midtrimester preterm premature rupture of the membranes: a retrospective cohort study. AB - BACKGROUND: Preterm premature rupture of membranes (PPROM) complicates 1% of all pregnancies and occurs in one third of all preterm deliveries. Midtrimester PPROM is often followed by spontaneous miscarriage and elective termination of ongoing pregnancies is offered in many countries. The aim of this retrospective descriptive cohort study was to investigate the natural history of midtrimester PPROM in a jurisdiction where termination of pregnancy in the absence of maternal compromise is unavailable. METHODS: Cases of midtrimester PPROM diagnosed between 14 and 23 + 6 weeks' gestation during April 2007 to June 2012 were identified following a manual search of all birth registers, pregnancy loss registers, annual reports, ultrasound reports, emergency room registers and neonatal death certificates at Cork University Maternity Hospital - a large (circa 8500 births per annum) tertiary referral maternity hospital in southwest Ireland. Cases where delivery occurred within 24 h of PPROM were excluded. RESULTS: The prevalence of midtrimester PPROM was 0.1% (42 cases/44,667 births). The mean gestation at PPROM was 18 weeks. The mean gestation at delivery was 20 + 5 weeks, with an average latency period of 13 days. Ten infants were born alive (23%; 10/42). The remainder (77%; 32/42) died in utero or intrapartum. Nine infants were resuscitated. Two infants survived to discharge. The overall mortality rate was 95% (40/42). Five women had clinical chorioamnionitis (12%; 5/42) but 69% demonstrated histological chorioamnionitis. One woman developed sepsis (2.4%; 1/42). Other maternal complications included requirement of intravenous antibiotic treatment (38%; 17/42), retained placenta (21%, 9/42) and post-partum haemorrhage (12%; 5/42). CONCLUSIONS: This study provides useful and contemporary data on midtrimester PPROM. Whilst fetal and neonatal mortality is high, long term survival is not impossible. The increased risk of maternal morbidity necessitates close surveillance. PMID- 26831897 TI - Equity impact of interventions to promote physical activity in older adults: protocol for a systematic review. AB - BACKGROUND: Public health strategies to promote physical activity among older adults are increasingly being implemented. However, it is not known whether these interventions are equally effective among all social groups of the older adult population. The objectives of the proposed systematic review are to (1) describe the extent to which effects on social inequalities are considered in studies evaluating the effectiveness of interventions to promote physical activity among older adults, (2) describe the methods used for measuring these effects, and (3) assess the implications of the equity related findings for health promotion research and practice. METHODS/DESIGN: MEDLINE, PsycINFO, CINAHL, CENTRAL, Physical Education Index, Social Science Citation Index, ASSIA, Sociological Abstracts, and IBSS databases as well as the German language journal Pravention und Gesundheitsforderung will be searched to identify experimental or observational quantitative studies evaluating the effects of interventions on self-reported or objectively measured physical activity among the general population of older adults (>= 50 years). English or German language peer reviewed journal articles published since 2005 will be included. Data on whether and how several social factors are considered for both the description of baseline characteristics of participants and for measuring intervention effectiveness will be extracted. The quality of studies will be assessed using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Results will be presented in a narrative synthesis. If feasible, harvest plots will be used to synthesize evidence about how intervention effects vary between different social groups. DISCUSSION: This systematic review will provide evidence on what is known about the effects of interventions on social inequalities in physical activity among older adults, which is a prerequisite for the prioritization of those interventions most likely to be effective across all social groups of this target population. Therefore, the results of this review will be of major interest to researchers, policy makers, and practitioners in the area of physical activity promotion for older adults. SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered with the PROSPERO international prospective register of systematic reviews (PROSPERO 2015 CRD42015025066). PMID- 26831898 TI - Parallel processing of cognitive and physical demands in left and right prefrontal cortices during smartphone use while walking. AB - BACKGROUND: Smartphone use while walking is becoming a public concern owing to an increased risk of falling that can result from cognitive-motor interference. We evaluated prefrontal cortex (PFC) activity in participants playing a smartphone game while walking, in order to elucidate the role of the PFC in the allocation of attention between physical and cognitive demands. Sixteen young and 15 older adults participated in this study. Participants were instructed to perform a touch number-selecting game on a smartphone while walking. The numbers of correct and mistake responses were analyzed as a measure of cognitive performance. Linear trunk accelerations were measured by another smartphone and analyzed for step time and acceleration magnitude as an assay of gait performance. PFC activity during the task was measured using a wearable 16-channel near-infrared spectroscopy system. RESULTS: Smartphone game playing while walking decreased the cognitive and gait performances compared with performances of single-task condition in older group more than in young group. There was no difference in PFC activation during smartphone use while walking between young and older groups, but age appeared to mediate correlation magnitude between PFC activation and changes in performance. In young adults, multiple regression analysis revealed an association of the right PFC with a reduction in acceleration magnitude (beta = 0.581, p = 0.023), and an association of the left PFC with an increase in game playing mistakes (beta = -0.556, p = 0.032) during smartphone use while walking. In older adults, multiple regression analysis revealed an association of the middle PFC with a prolongation of step time (beta = -0.550, p = 0.042) and of the left PFC with a reduction in acceleration magnitude (beta = -0.648, p = 0.012). CONCLUSION: In young adults, the left PFC inhibited inappropriate action and the right PFC stabilized gait performance. In older adults, a less-lateralized PFC activity pattern suppressed the deterioration of gait performance, but this resulted in impairment on a simultaneous cognitive task. These results suggest that lateralization of motor and cognitive tasks aids in efficient task completion during a complex action such as using a smartphone while walking. PMID- 26831899 TI - TAVR for patients with low risk for mortality is here for investigation. PMID- 26831900 TI - How to develop a successful chronic total occlusion percutaneous coronary intervention program. PMID- 26831901 TI - Time-related changes in neointimal tissue coverage of a novel Sirolimus eluting stent: Serial observations with optical coherence tomography. AB - BACKGROUND: DES has reduced rates of restenosis compared with BMS but it has been associated with delayed healing and increase of stent thrombosis. The aim of our study was to evaluate the vascular time-related changes following implantation of a new SES coated with an amorphous silicon carbide that allows faster re endothelisation (Orsiro-Biotronik). METHODS: This prospective registry enrolled STEMI-patients with multi-vessel disease, thus candidates for a two-step procedure. PCI of the culprit lesion was performed with at least one Orsiro stent that was OCT-analysed during the second-step procedure (deferred to 30,90 and 180 days). RESULTS: 16 of the 95 patients with MVD underwent an OCT evaluation of the study device implanted in the culprit lesion during the second-step staged procedure and were enrolled in the present Registry. A total of 3060-struts were analysed. The percentage of uncovered struts was 19.6% at30-days, 1.3% at90-days and 1.8% at180-days (p<0.001). The percentage of cross section with >=1 uncovered struts were 51.3% at30-days, 6.5% at90-days and 5.7% at180-days (p<0.001). The percentage of cross sections containing thrombus was 6.2% at30-days while no thrombus was detected both at90 and 180-days. CONCLUSIONS: Our data shows that the new Orsiro stent promotes early and persistent strut coverage with low peri strut thrombus. This pilot OCT evaluation might suggest a low incidence of late adverse events and anticipate safe outcome after early withdrawal of dual antiplatelet therapy. PMID- 26831902 TI - Coronary bypass graft perforation during percutaneous intervention. AB - INTRODUCTION: Coronary artery bypass grafts are prone to accelerated atherosclerosis and as such graft stenosis is frequently encountered in clinical practice. Complications specific to graft- PCI include no-reflow, distal embolization, stent restenosis and thrombosis. Graft perforation during PCI is a rare coomplication of the procedure. Published literature on the predictors of perforation and management strategy remains limited to anecdotal cases. METHOD: In this review we collected data on all cases of graft perforations reported in PubMed/Medline from 1987 to 2015. RESULT: 37 cases of graft perforation were reported. High risk grafts for perforations included, old grafts (14+/-7.8years) with more than 80% luminal stenosis. Perforations were noted after use of different cardiac devices and included stent placement (30%, N=11), balloon angioplasty (36%, N=14), post-dilation with non complaint balloon (16%, N=6), guide wire perforation (1 case), post IVUS imaging (1 case) and one case after use of thrombus extraction device. Average stent diameter of 3.7+/-0.7 mm, average balloon pressure of 15.5+/-5 atm and 3 or more balloon inflations commonly resulted in graft perforation. 78% of cases reported class III perforation. Covered stent implantation was strongly associated with controlling acute bleed after graft perforation than prolonged balloon inflation (p=0.0001). Majority of cases reported using covered stents (81%). Average stent diameter of 3.9+/-0.7mm, average stent length of 18.5+/-6mm and the average deployment pressure of 14+/-2atm were reported to be effective in controlling the bleed. 95% of the patients did well post procedure and with prolonged hospitalization (8+/ 4days). 24% of cases reported cardiac tamponade causing hemodynamic compromise including 2 peri-procedural deaths. CONCLUSION: Graft perforation can be effectively treated with covered stent grafts with good immediate results, short term outcome and acceptable peri-procedural risks. PMID- 26831903 TI - Dosimetric Factors and Toxicity in Highly Conformal Thoracic Reirradiation. AB - PURPOSE: We determined cumulative dose to critical structures, rates of toxicity, and outcomes following thoracic reirradiation. METHODS AND MATERIALS: We retrospectively reviewed our institutional database for patients treated between 2008 and 2014, who received thoracic reirradiation with overlap of 25% prescribed isodose lines. Patients received courses of hyperfractionated (n=5), hypofractionated (n=5), conventionally fractionated (n=21), or stereotactic ablative radiation therapy (n=51). Doses to critical structures were converted to biologically effective dose, expressed as 2 Gy per fraction equivalent dose (EQD2; alpha/beta = 2 for spinal cord; alpha/beta = 3 for other critical structures). RESULTS: We identified 82 courses (44 for retreatment) in 38 patients reirradiated at a median 16 months (range: 1-71 months) following initial RT. Median follow-up was 17 months (range: 3-57 months). Twelve- and 24 month overall survival rates were 79.6% and 57.3%, respectively. Eighteen patients received reirradiation for locoregionally recurrent non-small cell lung cancer with 12-month rates of local failure and regional recurrence and distant metastases rates of 13.5%, 8.1%, and 15.6%, respectively. Critical structures receiving >=75 Gy EQD2 included spinal cord (1 cm(3); n=1), esophagus (1 cm(3); n=10), trachea (1 cm(3); n=11), heart (1 cm(3); n=9), aorta (1 cm(3); n=16), superior vena cava (1 cm(3); n=12), brachial plexus (0.2 cm(3); n=2), vagus nerve (0.2 cm(3); n=7), sympathetic trunk (0.2 cm(3); n=4), chest wall (30 cm(3); n=12), and proximal bronchial tree (1 cm(3); n=17). Cumulative dose-volume (D cm(3)) toxicity following reirradiation data included esophagitis grade >=2 (n=3, D1 cm(3) range: 41.0-100.6 Gy), chest wall grade >=2 (n=4; D30 cm(3) range: 35.0 117.2 Gy), lung grade 2 (n=7; V20combined-lung range: 4.7%-21.7%), vocal cord paralysis (n=2; vagus nerve D0.2 cm(3) range: 207.5-302.2 Gy), brachial plexopathy (n=1; D0.2 cm(3) = 242.5 Gy), and Horner's syndrome (n=1; sympathetic trunk D0.2 cm(3) = 130.8 Gy). No grade >=4 toxicity was observed. CONCLUSIONS: Overlapping courses of reirradiation can be safely delivered with acceptable toxicity. Some toxicities occurred acutely at doses considered safe for a single course of therapy (esophagus). We observed rib fracture, brachial plexopathy, and Horner's syndrome for patients receiving high cumulative doses to corresponding critical structures. PMID- 26831904 TI - Anemia among indigenous women in Brazil: findings from the First National Survey of Indigenous People's Health and Nutrition. AB - BACKGROUND: Anemia is recognized as a major public health problem that disproportionately affects vulnerable populations. Indigenous women of reproductive age in Brazil are thought to be at high risk, but lack of nationwide data limits knowledge about the burden of disease and its main determinants. This study aimed to assess the prevalence of anemia and associated factors in this population using data from The First National Survey of Indigenous People's Health and Nutrition in Brazil. METHODS: Data were collected from Indigenous women between 15 and 49 years old based on a nationwide sample of villages. The outcomes of interest were hemoglobin levels (g/dL) and anemia (< 12 g/dL for nonpregnant and < 11 g/dL for pregnant women). Multilevel models were used to explore associations with contextual (village) and individual (household/woman) level variables. RESULTS: Based on data for 6692 Indigenous women, the nationwide mean hemoglobin level was 12.39 g/dL (95% CI: 12.29-12.50). Anemia prevalence was high (33.0%; 95% CI: 30.40-35.61%) and showed pronounced regional disparities. No village-level characteristics were associated with anemia or hemoglobin levels in the multilevel model. Even after controlling for upper level variables, socioeconomic status, parity, body mass index, and having been treated for malaria were associated with anemia and hemoglobin levels. CONCLUSION: The prevalence of anemia in Brazilian Indigenous women was 12% greater than the national estimates for women of reproductive age. Anemia prevalence and mean hemoglobin levels among Indigenous women appear to be partly explained by some previously recognized risk factors, such as socioeconomic status, body mass index, and malaria; however, part of the variability in these outcomes remains unexplained. Knowledge of health status and its potential determinants is essential to guide public policies aimed at controlling anemia burden in Indigenous communities. PMID- 26831905 TI - Identification of the dopamine transporter SLC6A3 as a biomarker for patients with renal cell carcinoma. AB - BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is among the most common human malignancies. METHODS: In order to provide better understanding of the molecular biology of ccRCC and to identify potential diagnostic/prognostic biomarker and therapeutic targets, we utilized a microarray to profile mRNA expression of corresponding normal and malignant renal tissues. Real-time PCR, Western Blot and immunohistochemistry were applied to study the expression of candidate biomarkers. ccRCC cell lines were treated with sertraline to inhibit the dopamine transporter SLC6A3. RESULTS: Differential expression of fourteen mRNAs, yet not studied in ccRCC in depth, was confirmed using qPCR (upregulation: SLC6A3, NPTX2, TNFAIP6, NDUFA4L2, ENPP3, FABP6, SPINK13; downregulation: FXYD4, SLC12A1, KNG1, NPHS2, SLC13A3, GCGR, PLG). Up-/downregulation was also confirmed for FXYD4, KNG1, NPTX2 and SLC12A1 by Western Blot on the protein level. In contrast to the mRNA expression, protein expression of the dopamine transporter SLC6A3 was lower in ccRCC compared to normal renal tissue. Immunohistochemistry indicated that this decrease was due to higher concentrations of SLC6A3 in the proximal tubules. Immunohistochemical analyses further demonstrated that high SLC6A3 expression in ccRCC tissue was correlated with a shorter period of recurrence-free survival following surgery. Treatment of ccRCC cells with the SLC6A3 inhibitor sertraline induced dose-dependent cell-death. CONCLUSION: Our study identified several novel biomarkers with diagnostic potential and further investigations on sertraline as therapeutic agent in ccRCC patients are warranted. PMID- 26831906 TI - The diversification of the basic leucine zipper family in eukaryotes correlates with the evolution of multicellularity. AB - BACKGROUND: Multicellularity evolved multiple times in eukaryotes. In all cases, this required an elaboration of the regulatory mechanisms controlling gene expression. Amongst the conserved eukaryotic transcription factor families, the basic leucine zipper (bZIP) superfamily is one of the most ancient and best characterised. This gene family plays a diversity of roles in the specification, differentiation and maintenance of cell types in plants and animals. bZIPs are also involved in stress responses and the regulation of cell proliferation in fungi, amoebozoans and heterokonts. RESULTS: Using 49 sequenced genomes from across the Eukaryota, we demonstrate that the bZIP superfamily has evolved from a single ancestral eukaryotic gene and undergone multiple independent expansions. bZIP family diversification is largely restricted to multicellular lineages, consistent with bZIPs contributing to the complex regulatory networks underlying differential and cell type-specific gene expression in these lineages. Analyses focused on the Metazoa suggest an elaborate bZIP network was in place in the most recent shared ancestor of all extant animals that was comprised of 11 of the 12 previously recognized families present in modern taxa. In addition this analysis identifies three bZIP families that appear to have been lost in mammals. Thus the ancestral metazoan and eumetazoan bZIP repertoire consists of 12 and 16 bZIPs, respectively. These diversified from 7 founder genes present in the holozoan ancestor. CONCLUSIONS: Our results reveal the ancestral opisthokont, holozoan and metazoan bZIP repertoire and provide insights into the progressive expansion and divergence of bZIPs in the five main eukaryotic kingdoms, suggesting that the early diversification of bZIPs in multiple eukaryotic lineages was a prerequisite for the evolution of complex multicellular organisms. PMID- 26831907 TI - Pasteur's Quadrant and the Provenance of Attestation: A Challenge for Addressing Society's Comprehension of Science. PMID- 26831908 TI - CIDANE: comprehensive isoform discovery and abundance estimation. AB - We present CIDANE, a novel framework for genome-based transcript reconstruction and quantification from RNA-seq reads. CIDANE assembles transcripts efficiently with significantly higher sensitivity and precision than existing tools. Its algorithmic core not only reconstructs transcripts ab initio, but also allows the use of the growing annotation of known splice sites, transcription start and end sites, or full-length transcripts, which are available for most model organisms. CIDANE supports the integrated analysis of RNA-seq and additional gene-boundary data and recovers splice junctions that are invisible to other methods. CIDANE is available at http://ccb.jhu.edu/software/cidane/. PMID- 26831910 TI - [Acute kidney injury after pediatric cardiac surgery: risk factors and outcomes. Proposal for a predictive model]. AB - OBJECTIVES: To characterize the epidemiology and risk factors for acute kidney injury (AKI) after pediatric cardiac surgery in our center, to determine its association with poor short-term outcomes, and to develop a logistic regression model that will predict the risk of AKI for the study population. METHODS: This single-center, retrospective study included consecutive pediatric patients with congenital heart disease who underwent cardiac surgery between January 2010 and December 2012. Exclusion criteria were a history of renal disease, dialysis or renal transplantation. RESULTS: Of the 325 patients included, median age three years (1 day-18 years), AKI occurred in 40 (12.3%) on the first postoperative day. Overall mortality was 13 (4%), nine of whom were in the AKI group. AKI was significantly associated with length of intensive care unit stay, length of mechanical ventilation and in-hospital death (p<0.01). Patients' age and postoperative serum creatinine, blood urea nitrogen and lactate levels were included in the logistic regression model as predictor variables. The model accurately predicted AKI in this population, with a maximum combined sensitivity of 82.1% and specificity of 75.4%. CONCLUSIONS: AKI is common and is associated with poor short-term outcomes in this setting. Younger age and higher postoperative serum creatinine, blood urea nitrogen and lactate levels were powerful predictors of renal injury in this population. The proposed model could be a useful tool for risk stratification of these patients. PMID- 26831911 TI - Proton beam therapy is as effective as radiotherapy in childhood brain cancer but less toxic, study shows. PMID- 26831912 TI - Aminoacyl-tRNA synthetases and the evolution of coded peptide synthesis: the Thioester World. AB - Coded peptide synthesis must have been preceded by a prebiotic stage, in which thioesters played key roles. Fossils of the Thioester World are found in extant aminoacyl-tRNA synthetases (AARSs). Indeed, studies of the editing function reveal that AARSs have a thiol-binding site in their catalytic modules. The thiol binding site confers the ability to catalyze aminoacyl~coenzyme A thioester synthesis and peptide bond formation. Genomic comparisons show that AARSs are structurally related to proteins involved in sulfur and coenzyme A metabolisms and peptide bond synthesis. These findings point to the origin of the amino acid activation and peptide bond synthesis functions in the Thioester World and suggest that the present-day AARSs had originated from ancestral forms that were involved in noncoded thioester-dependent peptide synthesis. PMID- 26831913 TI - Kidney disease in children: latest advances and remaining challenges. AB - To mark World Kidney Day 2016, Nature Reviews Nephrology invited six leading researchers to highlight the key advances and challenges within their specialist field of paediatric nephrology. Here, advances and remaining challenges in the fields of prenatal patterning, acute kidney injury, renal transplantation, genetics, cardiovascular health, and growth and nutrition, are all discussed within the context of paediatric and neonatal patients with kidney disease. Our global panel of researchers describe areas in which further studies and clinical advances are needed, and suggest ways in which research in these areas should progress to optimize renal care and long-term outcomes for affected patients. PMID- 26831914 TI - Antioxidant Potential and Ability of Phloroglucinol to Decrease Formation of Advanced Glycation End Products Increase Efficacy of Sildenafil in Diabetes Induced Sexual Dysfunction of Rats. AB - INTRODUCTION: Diabetes-induced sexual dysfunction is associated with an increase in oxidative stress. Scavengers of reactive oxygen species (ROS) have been shown to reduce oxidative stress and aid in the management of sexual dysfunction in diabetes. AIM: The aim of the study was to test the hypothesis that antioxidant, which scavenge ROS and reduce formation of advanced glycation end products (AGEs), can potentiate efficacy of phosphodiesterase type 5 inhibitors in diabetes-induced sexual dysfunction that is associated with oxidative stress. MATERIALS AND METHODS: Effect of phloroglucinol and sildenafil on serum glucose level, sexual function, penile smooth muscle : collagen ratio, and phenylephrine precontracted corpus cavernosum smooth muscle (CCSM) was studied. The ability of phloroglucinol to reduce the formation of AGEs and its ability to scavenge 2,2 diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) was also evaluated. MAIN OUTCOME MEASURES: Antioxidant potential of phloroglucinol was studied in addition to its effect on diabetes-induced sexual dysfunction in presence and absence of sildenafil. RESULTS: Phloroglucinol (50 mg/kg, p.o.) significantly decreased serum glucose level and increased sexual function in streptozotocin-induced diabetic rats when compared with diabetic control rats. Sildenafil (5 mg/kg, p.o.) had no effect on glycemia but significantly increased sexual function of diabetic rats. Coadministration of phloroglucinol increased the efficacy of sildenafil by improving sexual function. Treatment of diabetic rats with phloroglucinol + sildenafil maintained smooth muscle : collagen levels similar to that of normal rat penile tissue. Phloroglucinol decreased formation of AGEs and significantly scavenged DPPH radical activity in vitro. Sildenafil relaxed isolated CCSM of normal rat and diabetic rat significantly, but phloroglucinol did not show any significant effect. Phloroglucinol also inhibited human CYP3A4 enzyme activity in vitro. CONCLUSION: Phloroglucinol coadministration increases efficacy of sildenafil in diabetes-induced sexual dysfunction. However, further studies are required to ascertain the benefits of phloroglucinol owing to its undesirable CYP3A4 inhibition activity. PMID- 26831915 TI - The Differential Susceptibility Hypothesis: Sensitivity to the Environment for Better and for Worse. PMID- 26831917 TI - Psychological Stress Activates the Inflammasome via Release of Adenosine Triphosphate and Stimulation of the Purinergic Type 2X7 Receptor. AB - BACKGROUND: The mechanisms underlying stress-induced inflammation that contribute to major depressive disorder are unknown. We examine the role of the adenosine triphosphate (ATP)/purinergic type 2X7 receptor (P2X7R) pathway and the NLRP3 (nucleotide-binding, leucine-rich repeat, pyrin domain containing 3) inflammasome in interleukin (IL)-1beta and depressive behavioral responses to stress. METHODS: The influence of acute restraint stress on extracellular ATP, glutamate, IL 1beta, and tumor necrosis factor alpha in hippocampus was determined by microdialysis, and the influence of acute restraint stress on the NLRP3 inflammasome was determined by western blot analysis. The influence of P2X7R antagonist administration on IL-1beta and tumor necrosis factor alpha and on anxiety and depressive behaviors was determined in the chronic unpredictable stress rodent model. The role of the NLRP3 inflammasome was determined by analysis of Nlrp3 null mice. RESULTS: Acute restraint stress rapidly increased extracellular ATP, an endogenous agonist of P2X7R; the inflammatory cytokine IL 1beta; and the active form of the NLRP3 inflammasome in the hippocampus. Administration of a P2X7R antagonist completely blocked the release of IL-1beta and tumor necrosis factor alpha, another stress-induced cytokine, and activated NLRP3. Moreover, P2X7R antagonist administration reversed the anhedonic and anxiety behaviors caused by chronic unpredictable stress exposure, and deletion of the Nlrp3 gene rendered mice resistant to development of depressive behaviors caused by chronic unpredictable stress. CONCLUSIONS: These findings demonstrate that psychological "stress" is sensed by the innate immune system in the brain via the ATP/P2X7R-NLRP3 inflammasome cascade, and they identify novel therapeutic targets for the treatment of stress-related mood disorders and comorbid illnesses. PMID- 26831918 TI - Surface properties of Ti-35Nb-7Zr-5Ta: Effects of long-term immersion in artificial saliva and fluoride solution. AB - STATEMENT OF PROBLEM: The mechanical properties of new titanium alloys with an elastic modulus closest to cortical bone have been studied. However, potentially damaging conditions experienced in the oral cavity, such as fluoride ions, can initiate a localized or crevice process of corrosive degradation in the alloy surfaces. PURPOSE: The purpose of this in vitro study was to evaluate the effects of long-term immersion in artificial saliva or in fluoride solution on mean roughness (Ra), Vickers hardness, and topography of the new titanium alloy Ti 35Nb-7Zr-5Ta (TNZT) compared with those of cp Ti and Ti-6Al-4V (TAV). MATERIAL AND METHODS: Disks (N=210) were divided into cp Ti, TAV, and TNZT and subdivided according to the following treatments: no immersion (N(-), control), immersion in artificial saliva (S), and immersion in fluoride (F) during periods equivalent to 5, 10, 15, and 20 years. The Ra and Vickers hardness were measured with a profilometer and a hardness tester. The topography was analyzed by scanning electronic microscopy. Data were compared using the Kruskal-Wallis and Dunn tests (alpha=.05). RESULTS: Values of Ra and hardness were significantly different among the metals (Ra: TAV16)-abeo-3,5,8,12,15 abietapentaen-2,7,11,14-tetraone (1), and four known diterpenoids, teuvincenone F (2), uncinatone (3), coleon U (4), coleon U-12-methyl ether (5). These structures were identified by using spectroscopic methods, including UV, MS, 1D and 2D NMR experiments. This is the first report of these compounds being isolated from a Pestalotiopsis species. The cytotoxic activities of the compounds were evaluated, and compounds 1 and 3 demonstrated cytotoxic activities against the HL-60 tumour cell line (IC50 < 20 MUM). PMID- 26831946 TI - [Severe cutaneous drug reactions to misused griseofulvin: 2 cases]. AB - BACKGROUND: Griseofulvin is an antifungal drug known to cause drug rash. However, it is widely prescribed outside its classic indications. Herein, we describe 2 cases in which griseofulvin was prescribed for off-label indications. PATIENTS AND METHODS: Case No. 1. A 51-year-old woman was referred to the department of internal medicine for management of Stevens-Johnson Syndrome (SJS). The symptoms appeared 17 days after she had taken griseofulvin for inguinal intertrigo. Case No. 2. A 19-year-old female patient consulted for toxic epidermal necrolysis (TEN) affecting 30% of her body surface, with a positive Nikolsky sign and severe mucosal lesions. These symptoms appeared 9 days after she began taking griseofulvin, which had initially been prescribed for her husband for mycosis. DISCUSSION: Toxic epidermal necrolysis, a condition chiefly of drug-related origin, is a severe mucocutaneous syndrome characterized by massive keratinocytic apoptosis. Although there are few scientific publications referring to griseofulvin-induced drug eruption, they deserve to be mentioned since this drug is widely used for purposes other than the approved indications and can cause life-threatening reactions. CONCLUSION: We report two cases of toxic epidermal necrolysis related to the misuse of griseofulvin. It is important to bear in mind the precautions for use of oral antifungal drugs, which are strictly reserved for use against resistant or diffuse forms of mucocutaneous fungal infections. PMID- 26831948 TI - In Situ Study of Strain-Dependent Ion Conductivity of Stretchable Polyethylene Oxide Electrolyte. AB - There is a strong need in developing stretchable batteries that can accommodate stretchable or irregularly shaped applications including medical implants, wearable devices and stretchable electronics. Stretchable solid polymer electrolytes are ideal candidates for creating fully stretchable lithium ion batteries mainly due to their mechanical and electrochemical stability, thin-film manufacturability and enhanced safety. However, the characteristics of ion conductivity of polymer electrolytes during tensile deformation are not well understood. Here, we investigate the effects of tensile strain on the ion conductivity of thin-film polyethylene oxide (PEO) through an in situ study. The results of this investigation demonstrate that both in-plane and through-plane ion conductivities of PEO undergo steady and linear growths with respect to the tensile strain. The coefficients of strain-dependent ion conductivity enhancement (CSDICE) for in-plane and through-plane conduction were found to be 28.5 and 27.2, respectively. Tensile stress-strain curves and polarization light microscopy (PLM) of the polymer electrolyte film reveal critical insights on the microstructural transformation of stretched PEO and the potential consequences on ionic conductivity. PMID- 26831949 TI - Pyoderma gangrenosum, acne, suppurative hidradenitis (PASH) and polycystic ovary syndrome: Coincidentally or aetiologically connected? AB - The clinical triad of pyoderma gangrenosum, acne conglobata and hidradenitis suppurativa has been named PASH syndrome. Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and inflammation. Hidradenitis suppurativa, like acne vulgaris, may be a feature of hyperandrogenism. Obesity may be associated with both hidradenitis suppurativa and PCOS. We describe a possible association between PASH syndrome and PCOS. PMID- 26831950 TI - Seasonal induction of alternative principal pathway for rose flower scent. AB - Ecological adaptations to seasonal changes are often observed in the phenotypic traits of plants and animals, and these adaptations are usually expressed through the production of different biochemical end products. In this study, ecological adaptations are observed in a biochemical pathway without alteration of the end products. We present an alternative principal pathway to the characteristic floral scent compound 2-phenylethanol (2PE) in roses. The new pathway is seasonally induced in summer as a heat adaptation that uses rose phenylpyruvate decarboxylase (RyPPDC) as a novel enzyme. RyPPDC transcript levels and the resulting production of 2PE are increased time-dependently under high temperatures. The novel summer pathway produces levels of 2PE that are several orders of magnitude higher than those produced by the previously known pathway. Our results indicate that the alternative principal pathway identified here is a seasonal adaptation for managing the weakened volatility of summer roses. PMID- 26831951 TI - Fatal Central Nervous System Disease Following First Infliximab Infusion in a Child With Inflammatory Bowel Disease. AB - BACKGROUND: Infliximab is used in the treatment of inflammatory bowel disease. Previously reported neurological complications include central and peripheral demyelinating disorders and neuropathies occurring months into therapy. PATIENT DESCRIPTION: A seven-year-old boy diagnosed with ulcerative colitis and primary sclerosing cholangitis received infliximab. Six hours following his uneventful infusion, he awoke with headache and emesis and rapidly became obtunded. Neurological examination revealed minimally reactive pupils and otherwise absent brainstem reflexes. Cranial computed tomography revealed hypodense lesions in the cerebral hemispheres, cerebellum, and pons accompanied by hemorrhage. Magnetic resonance imaging showed diffusion restriction concerning for ischemia with areas of ring enhancement suggestive of inflammation. Vessel imaging was normal, and cerebrospinal fluid and serum studies showed only an extremely elevated level of d-dimer. Echocardiogram showed depressed ventricular function but neither intracardiac shunt nor thrombus. Within four days he met criteria for brain death. Autopsy was refused. CONCLUSIONS: This is the first report of a fulminant, fatal central nervous system process to occur after an initial dose of infliximab. The differential diagnosis includes multifocal arterial strokes and a devastating demyelinating process. PMID- 26831952 TI - Attention Deficit Hyperactivity Disorder in Adolescents With Epilepsy. AB - BACKGROUND: We examined attention-deficit hyperactivity disorder in adolescents with epilepsy and the association with seizure-related and sociodemographic variables. METHODS: Strengths and Weakness of Attention-Deficit Hyperactivity Disorder Symptoms and Normal Behaviors rating scale was administered to 122 children with epilepsy and 50 children with asthma, aged 10 to 18 years attending mainstream schools. RESULTS: Twenty-nine (23.7%) adolescents with epilepsy compared with five (10%) with asthma had attention deficit hyperactivity disorder (P = 0.037). Adolescents with epilepsy had a significantly higher score in the inattention subscale when compared with those with asthma (-0.25 +/- 1.2 vs -0.64 +/- 1.07, P = 0.049). Combined subtype was most frequent in the epilepsy group. Oppositional defiant disorders were more prevalent in those having attention deficit hyperactivity disorder. Psychiatric assistance had only been provided to one third of our patients with epilepsy and attention deficit hyperactivity disorder at the time of study. There was a negative correlation between attention deficit hyperactivity disorder scores and age of seizure onset. A positive correlation was observed between the number of antiepileptic drugs and the inattentive subscale score. The impact of various correlates on individual subtypes was not identical. Independent risk factors associated with attention deficit hyperactivity disorder were medical comorbidities (odds ratio = 12.82, 95% confidence interval 4.44, 37.03, P < 0.0001) and age at seizure onset (odds ratio = 0.73, 95% confidence interval 0.56, 0.94, P = 0.016). CONCLUSIONS: Attention deficit hyperactivity disorder is overrepresented in adolescents with epilepsy; screening for its symptoms should be an integral part of management in adolescents with epilepsy. PMID- 26831953 TI - Fast Optical Chemical and Structural Classification of RNA. AB - As more biological activities of ribonucleic acids continue to emerge, the development of efficient analytical tools for RNA identification and characterization is necessary to acquire an in-depth understanding of their functions and chemical properties. Herein, we demonstrate the capacity of label free direct surface-enhanced Raman scattering (SERS) analysis to access highly specific structural information on RNAs at the ultrasensitive level. This includes the recognition of distinctive vibrational features of RNAs organized into a variety of conformations (micro-, fully complementary duplex-, small interfering- and short hairpin-RNAs) or characterized by subtle chemical differences (single-base variances, nucleobase modifications and backbone composition). This method represents a key advance in the ribonucleic acid analysis and will have a direct impact in a wide range of different fields, including medical diagnosis, drug design, and biotechnology, by enabling the rapid, high-throughput, simple, and low-cost identification and classification of structurally similar RNAs. PMID- 26831954 TI - How potentially predictable are midlatitude ocean currents? AB - Predictability of atmospheric variability is known to be limited owing to significant uncertainty that arises from intrinsic variability generated independently of external forcing and/or boundary conditions. Observed atmospheric variability is therefore regarded as just a single realization among different dynamical states that could occur. In contrast, subject to wind, thermal and fresh-water forcing at the surface, the ocean circulation has been considered to be rather deterministic under the prescribed atmospheric forcing, and it still remains unknown how uncertain the upper-ocean circulation variability is. This study evaluates how much uncertainty the oceanic interannual variability can potentially have, through multiple simulations with an eddy resolving ocean general circulation model driven by the observed interannually varying atmospheric forcing under slightly different conditions. These ensemble "hindcast" experiments have revealed substantial uncertainty due to intrinsic variability in the extratropical ocean circulation that limits potential predictability of its interannual variability, especially along the strong western boundary currents (WBCs) in mid-latitudes, including the Kuroshio and its eastward extention. The intrinsic variability also greatly limits potential predictability of meso-scale oceanic eddy activity. These findings suggest that multi-member ensemble simulations are essential for understanding and predicting variability in the WBCs, which are important for weather and climate variability and marine ecosystems. PMID- 26831955 TI - High power, high repetition rate, few picosecond Nd:LuVO4 oscillator with cavity dumping. AB - We investigate the potential use of Nd:LuVO4 in high average power, high repetition rate ultrafast lasers. Maximum mode-locked average power of 28 W is obtained at the repetition rate of 58 MHz. The shortest pulse duration is achieved at 4 ps without dispersion compensation. With a cavity dumping technique, the pulse energy is scaling up to 40.7 MUJ at 300 kHz and 14.3 MUJ at 1.5 MHz. PMID- 26831956 TI - Measurement of power spectral density of broad-spectrum visible light with heterodyne near field scattering and its scalability to betatron radiation. AB - We exploit the speckle field generated by scattering from a colloidal suspension to access both spatial and temporal coherence properties of broadband radiation. By applying the Wiener-Khinchine theorem to the retrieved temporal coherence function, information about the emission spectrum of the source is obtained in good agreement with the results of a grating spectrometer. Experiments have been performed with visible light. We prove more generally that our approach can be considered as a tool for modeling a variety of cases. Here we discuss how to apply such diagnostics to broad-spectrum betatron radiation produced in the laser driven wakefield accelerator under development at SPARC LAB facility in Frascati. PMID- 26831957 TI - Influence of gating and of the gate shape on the penetration capacity of range gated active imaging in scattering environments. AB - Range-gated active imaging is a well-known technique used for night vision or for vision enhancement in scattering environments. A lot of papers have been published, in which the performance enhancement of range gating has been demonstrated. However, there are no studies which systematically investigate and quantify the real gain brought by range gating, in comparison with a classical imaging system, in controlled smoke densities. In this paper, a systematic investigation of the performance enhancement of range-gated viewing is presented in comparison with a color camera representing the human vision. The influence of range gating and of the gate shape is studied. We have been able to demonstrate that a short-wave infrared (SWIR) range-gated active imaging system can enhance by a factor of 6.9 the penetration depth in dense smoke. On the other hand, we have shown that the combination of a short pulse with a short integration time gives better contrasted images in dense scattering media. PMID- 26831958 TI - Ultra-compact Watt-level flat supercontinuum source pumped by noise-like pulse from an all-fiber oscillator. AB - We demonstrate Watt-level flat visible supercontinuum (SC) generation in photonic crystal fibers, which is directly pumped by broadband noise-like pulses from an Yb-doped all-fiber oscillator. The novel SC generator is featured with elegant all-fiber-integrated architecture, high spectral flatness and high efficiency. Wide optical spectrum spanning from 500 nm to 2300 nm with 1.02 W optical power is obtained under the pump of 1.4 W noise-like pulse. The flatness of the spectrum in the range of 700 nm~1600 nm is less than 5 dB (including the pump residue). The exceptional simplicity, economical efficiency and the comparable performances make the noise-like pulse oscillator a competitive candidate to the widely used cascade amplified coherent pulse as the pump source of broadband SC. To the best of our knowledge, this is the first demonstration of SC generation which is directly pumped by an all-fiber noise-like pulse oscillator. PMID- 26831959 TI - Design and fabrication of complicated diffractive optical elements on multiple curved surfaces. AB - Fabrication of multiple arbitrary diffractive optical elements (DOEs) on multiple curved surfaces is always a challenge; here we propose an effective optimization method to fabricate complicated DOEs on several curved surfaces at the same time. First we design phase distribution to modulate complicated three-dimensional (3D) intensity distribution on multiple curved surfaces simultaneously, and then by exposure, the intensity distribution is transferred into the pure-phase or depth distribution. Numerical simulations and optical fabrication are performed for different intensity distributions: 3D binary patterns and 3D gray level patterns, on two or three curved surfaces, and both are in nice agreement. Since multiple DOEs are fabricated on curved surfaces simultaneously, the collimation of different curved surfaces is avoided, and it could improve the fabrication efficiency. It is expected that this proposed method would be employed in various precision 3D optical fabrication and processing in the future. PMID- 26831960 TI - Double fiber probe with a single fiber Bragg grating based on the capillary driven self-assembly fabrication method for dimensional measurement of micro parts. AB - Focusing on the ultra-precision dimensional measurement of parts with micro-scale dimensions and high aspect ratios, a two-dimensional double fiber probe with a single fiber Bragg grating (DS-FBG probe) is investigated in detail in this paper. The theoretical analysis of the sensing principle is verified by spectrum simulations of the DS-FBG probe with a modified transfer matrix method using the strain distribution within the DS-FBG probe. The fabrication process and physical principle of the capillary-driven self-assembly of double fibers in the UV adhesive with a low viscosity are demonstrated. Experimental results indicate that resolutions of 30 nm in radial direction and 15 nm in axial direction can be achieved, and the short-term displacement drifts within 90 seconds are 28.0 nm in radial direction and 7.9 nm in axial direction, and the long-term displacement drifts within 1 hour are 61.3 nm in radial direction and 17.3 nm in axial direction. The repeatability of the probing system can reach 60 nm and the measurement result of a standard nozzle is 300.49 MUm with a standard deviation of 20 nm. PMID- 26831961 TI - Vibration-insensitive measurements of the thickness profile of large glass panels. AB - We propose and realize a modified spectral-domain interferometer to measure the physical thickness profile and group refractive index distribution of a large glass substrate simultaneously. The optical layout was modified based on a Mach Zehnder type interferometer, which was specially adopted to be insensitive to mechanical vibration. According to the measurement results of repeated experiments at a length of 820 mm along the horizontal axis, the standard deviations of the physical thickness and group refractive index were calculated to be 0.173 MUm and 3.4 * 10(-4), respectively. To verify the insensitivity to vibration, the physical thickness values were monitored at a stationary point while the glass panel was swung at an amplitude exceeding 20 mm. The uncertainty components were evaluated, and the combined measurement uncertainty became 161 nm (k = 1) for a glass panel with a nominal thickness of 0.7 mm. PMID- 26831962 TI - 25-Gb/s broadband silicon modulator with 0.31-V.cm VpiL based on forward-biased PIN diodes embedded with passive equalizer. AB - We investigated the broadband operations of a silicon Mach-Zehnder modulator (MZM) based on a forward-biased-PIN diode. The phase shifter was integrated with a passive-circuit equalizer to compensate for the narrowband characteristics of the diodes, which consists of a simple resistance of doped silicon and a parallel plate metal capacitance. The device structure was simple and fabricated using standard CMOS processes. The measured results for a 50-Omega driver indicated there was a small VpiL of 0.31 V.cm and a flat frequency response for a 3-dB bandwidth (f(3dB)) of 17 GHz, which agree well with the designed values. A 25 Gb/s large-signal operation was obtained using binary signals without pre emphasis. The modulator showed a linear modulation property to the applied voltage, due to the metal capacitance of the equalizer. PMID- 26831963 TI - Investigation of the silicon vacancy color center for quantum key distribution. AB - Single photon sources (SPS) are crucial for quantum key distribution. Here we demonstrate a stable triggered SPS at 738 nm with linewidth less than 5 nm at room temperature based on a negatively charged single silicon vacancy color center. Thanks to the short photon duration of about 1.3-1.7 ns, by using high repetition pulsed excitation at 30 MHz, the triggered single photon source generates 16.6 kcounts/s. And we discuss the feasibility of this triggered SPS in the application of quantum key distribution. PMID- 26831964 TI - Error-free DWDM transmission and crosstalk analysis for a silicon photonics transmitter. AB - Individual channels of a five-channel microring silicon photonics transmitter are used for bit error ratio analysis and demonstrate error-free transmission at 10Gb/s. Two channels of the same transmitter are concurrently modulated using an 80GHz channel spacing comb laser and demonstrate open eye diagrams at 10Gb/s and 12.5Gb/s. Finally, concurrent modulation with tunable lasers is done to quantify optical power penalty for link bit error ratio versus channel spacing from +100GHz to -100GHz. When using a comb laser for concurrent modulation, no direct power penalty is observed for an 80GHz channel separation. PMID- 26831965 TI - Deterministic generation of bright single resonance fluorescence photons from a Purcell-enhanced quantum dot-micropillar system. AB - We report on the observation of bright emission of single photons under pulsed resonance fluorescence conditions from a single quantum dot (QD) in a micropillar cavity. The brightness of the QD fluorescence is greatly enhanced via the coupling to the fundamental mode of a micropillar, allowing us to determine a single photon extraction efficiency of (20.7 +/- 0.8) % per linear polarization basis. This yields an overall extraction efficiency of (41.4 +/- 1.5) % in our device. We observe the first Rabi-oscillation in a weakly coupled quantum dot micropillar system under coherent pulsed optical excitation, which enables us to deterministically populate the excited QD state. In this configuration, we probe the single photon statistics of the device yielding g(2)(0) = 0.072 +/- 0.011 at a QD-cavity detuning of 75 MUeV. PMID- 26831966 TI - Enhancing the radiative emission rate of single molecules by a plasmonic nanoantenna weakly coupled with a dielectric substrate. AB - Enhancing the spontaneous emission of single emitters has been an important subject in nano optics in the past decades. For this purpose, plasmonic nanoantennas have been proposed with enhancement factors typically larger than those achievable with optical cavities. However, the intrinsic ohmic losses of plasmonic structures also introduce an additional nonradiative decay channel, reducing the quantum yield. Here we report on experimental studies of a weakly coupled dielectric substrate and a plasmonic nanoantenna for enhancing the radiative decay rate of single terrylene molecules embedded in an ultrathin organic film. We systematically investigate how the refractive index of the dielectric substrate affects the lifetime and the quantum efficiency and show that the coupled structure could moderately enhance the radiative decay rate while maintaining a high quantum efficiency. PMID- 26831967 TI - Is ghost imaging intrinsically more powerful against scattering? AB - We demonstrated experimental comparison between ghost imaging and traditional non correlated imaging under disturbance of scattering. Ghost imaging appears more robust. The quality of ghost imaging does not change much when the scattering is getting stronger, while that of traditional imaging declines dramatically. A concise model is developed to explain the superiority of ghost imaging. Due to its robustness against scattering, ghost imaging will be useful in harsh environment. PMID- 26831968 TI - Supermode Bragg grating combined Mach-Zehnder interferometer for temperature strain discrimination. AB - We report on a compact sensor by integrating a Mach-Zehnder interference and a cladding Bragg grating in a same section of all-solid photonic bandgap fiber. Theoretical investigation reveals that the Bragg grating resonance stems from the coupling of counter-propagating cladding LP01-like supermodes and the Mach Zehnder interference works between a LP01-like supermode and LP01 core mode. Compared with the interference fringe, such supermode grating dip responses to axial strain in a more sensitive and opposite-direction manner. Whereas, the interference fringe shows a higher temperature sensitivity than the supermode grating dip. By means of these different responses, this device finds a useful application in the discrimination of temperature and axial strain. PMID- 26831969 TI - Fabry-Perot based metal-dielectric multilayered filters and metamaterials. AB - The traditional three-layered metal-dielectric-metal Fabry-Perot filter is developed as a new metal-dielectric multilayered band-pass filter. Our design method allows metal and dielectric films to be alternatively arranged to achieve a narrow and high transmission peak and the peak height remains unchanged for any number of metal films arranged in the multilayer. Furthermore, the equivalent refractive index of a subwavelength metal-dielectric multilayer could be negative real at the passband of the filter and such metamaterial exhibits stronger figure of merit than a previous result. By choosing a material with high refractive index as the dielectric film, such metamaterial exhibits a pass band that depends weakly on the angle of incidence. PMID- 26831970 TI - Enhancement of soft X-ray reflectivity and interface stability in nitridated Pd/Y multilayer mirrors. AB - Pd/Y multilayer mirrors operating in the soft X-ray region are characterized by a high theoretical reflectance, reaching 65% at normal incidence in the 8-12 nm wavelength range. However, a severe intermixing of neighboring Pd and Y layers results in an almost total disappearance of the interfaces inside the multilayer structures fabricated by direct current magnetron sputtering and thus a dramatic reflectivity decrease. Based on grazing incidence X-ray reflectometry and X-ray photoelectron spectroscopy, we demonstrate that the stability of the interfaces in Pd/Y multilayer structures can be essentially improved by adding a small amount of nitrogen (4-8%) to the working gas (Ar). High resolution transmission electron microscopy shows that the interlayer width is only 0.9 nm and 0.6 nm for Y(N)-on-Pd(N) and Pd(N)-on-Y(N) interfaces, respectively. A well-defined crystalline texture of YN (200) is observed on the electron diffraction pattern. As a result, the measured reflectance of the Pd(N)/Y(N) multilayer achieves 30% at lambda = 9.3 nm. The peak reflectivity value is limited by the remaining interlayers and the formation of the YN compound inside the yttrium layers, resulting in an increased absorption. PMID- 26831971 TI - Embedded pupil function recovery for Fourier ptychographic microscopy: erratum. AB - In the original paper, the line width of the resolution target (which corresponds to half-pitch resolution) was used to characterize the resolution of our microscope system. However, we think that full-pitch resolution offers a better definition of the imaging system's resolution limit. In this erratum, we list specific sections from the manuscript that used half-pitch resolution and correct them accordingly. PMID- 26831972 TI - Ignition of an automobile engine by high-peak power Nd:YAG/Cr4+:YAG laser-spark devices. AB - Laser sparks that were built with high-peak power passively Q-switched Nd:YAG/Cr(4+):YAG lasers have been used to operate a Renault automobile engine. The design of such a laser spark igniter is discussed. The Nd:YAG/Cr(4+):YAG laser delivered pulses with energy of 4 mJ and 0.8-ns duration, corresponding to pulse peak power of 5 MW. The coefficients of variability of maximum pressure (COV(Pmax)) and of indicated mean effective pressure (COV(IMEP)) and specific emissions like hydrocarbons (HC), carbon monoxide (CO), nitrogen oxides (NO(x)) and carbon dioxide (CO2) were measured at various engine speeds and high loads. Improved engine stability in terms of COV(Pmax) and COV(Pmax) and decreased emissions of CO and HC were obtained for the engine that was run by laser sparks in comparison with classical ignition by electrical spark plugs. PMID- 26831973 TI - Monolithic device for modelocking and stabilization of frequency combs. AB - We demonstrate a device that integrates a III-V semiconductor saturable absorber mirror with a graphene electro-optic modulator, which provides a monolithic solution to modelocking and noise suppression in a frequency comb. The device offers a pure loss modulation bandwidth exceeding 5 MHz and only requires a low voltage driver. This hybrid device provides not only compactness and simplicity in laser cavity design, but also small insertion loss, compared to the previous metallic-mirror-based modulators. We believe this work paves the way to portable and fieldable phase-coherent frequency combs. PMID- 26831974 TI - Exact dipolar moments of a localized electric current distribution. AB - The multipolar decomposition of current distributions is used in many branches of physics. Here, we obtain new exact expressions for the dipolar moments of a localized electric current distribution. The typical integrals for the dipole moments of electromagnetically small sources are recovered as the lowest order terms of the new expressions in a series expansion with respect to the size of the source. All the higher order terms can be easily obtained. We also provide exact and approximated expressions for dipoles that radiate a definite polarization handedness (helicity). Formally, the new exact expressions are only marginally more complex than their lowest order approximations. PMID- 26831975 TI - Giant plasmonic circular dichroism in Ag staircase nanostructures. AB - We demonstrate large circular dichroism (CD) in the visible range resulting from electromagnetic couplings in three-dimensional Ag staircase nanostructures. Analytical calculations using effective constitutive parameters show that the CD originates from chiral resonances of the staircase in which the induced magnetic dipole moment has components parallel or antiparallel to the induced electric dipole moment. The strength of the coupling as well as the CD can be tuned by varying the configuration (e.g. the strip width) of staircase nanostructure. More importantly we are able to realize such chiral resonances with large CD in the visible range in topologically similar chiral nanostructures fabricated using a simple shadowing vapor deposition method. Our simple staircase model demonstrates the effect of couplings between electric and magnetic dipole moments in producing large chiral responses in 3D nanostructures and can enhance the understanding of hybrid chiral optical systems. PMID- 26831976 TI - Photonic spin filter with dielectric metasurfaces. AB - We propose a photonic spin filter whose structure is similar to that of conventional spatial filter, but the two plano-convex lenses are replaced by Pancharatnam-Berry phase ones. The dielectric metasurface with high transmission and conversion efficiency is designed to work as Pancharatnam-Berry phase lens. The photonic spin filter can sort desired spin photons from the input beam with mixed spin states, and thereby facilitate possible applications in spin-based photonics. PMID- 26831977 TI - Scheme for on-chip verification of transverse mode entanglement using the electro optic effect. AB - A key ingredient in emerging quantum-enhanced technologies is the ability to coherently manipulate and detect superpositions of basis states. In integrated optics implementations, transverse spatial modes supported by multimode structures offer an attractive carrier of quantum superpositions. Here we propose an integrated dynamic mode converter based on the electro-optic effect in nonlinear channel waveguides for deterministic transformations between mutually non-orthogonal bases of spatial modes. We theoretically show its capability to demonstrate a violation of a Bell-type Clauser-Horne-Shimony-Holt inequality by measuring spatially mode-entangled photon pairs generated by an integrated photon pair source. The proposed configuration, numerically studied for the potassium titanyl phosphate (KTP) material, can be easily implemented using standard integrated optical fabrication technology. PMID- 26831978 TI - Generation and propagation of a vector cosine-Gaussian correlated beam with radial polarization. AB - Scalar cosine-Gaussian-correlated Schell-model (CGCSM) beams of circular or rectangular symmetry were introduced just recently. In this paper, a new kind of partially coherent vector beam named vector CGCSM beam with radial polarization (i.e., radially polarized CGCSM beam) is introduced. The realizability conditions for a radially polarized CGCSM source and the beam condition for radiation generated by such source are derived. The statistical properties, such as the average intensity, the degree of coherence, the degree of polarization and the state of polarization, of a radially polarized CGCSM beam focused by a thin lens are analyzed in detail. It is found that the statistical properties of a radially polarized CGCSM beam are quite different from those of a conventional radial polarized partially coherent beam with Gaussian correlated Schell-model function. Furthermore, we first report experimental generation of a radially polarized CGCSM beam and measure its focusing properties. Our experimental results are consistent with the theoretical predictions. PMID- 26831979 TI - Single-shot high-resolution characterization of optical pulses by spectral phase diversity. AB - The concept of spectral phase diversity is proposed and applied to the temporal characterization of optical pulses. The experimental trace is composed of the measured power of a plurality of ancillary optical pulses derived from the pulse under test by adding known amounts of chromatic dispersion. The spectral phase of the pulse under test is retrieved by minimizing the error between the experimental trace and a trace calculated using the known optical spectrum and diagnostic parameters. An assembly composed of splitters and dispersive delay fibers has been used to generate 64 ancillary pulses whose instantaneous power can be detected in a single shot with a high-bandwidth photodiode and oscilloscope. The diagnostic is experimentally shown to accurately characterize pulses from a chirped-pulse-amplification system when its stretcher is detuned from the position for optimal recompression. Pulse-shape reconstruction for pulses shorter than the photodetection impulse response has been demonstrated. Various investigations of the performance with respect to the number of ancillary pulses and the range of chromatic dispersion generated in the diagnostic are presented. PMID- 26831980 TI - Tbits/s physical random bit generation based on mutually coupled semiconductor laser chaotic entropy source. AB - Using two mutually coupled semiconductor lasers (MC-SLs) outputs as chaotic entropy sources, a scheme for generating Tbits/s ultra-fast physical random bit (PRB) is demonstrated and analyzed experimentally. Firstly, two entropy sources originating from two chaotic outputs of MC-SLs are obtained in parallel. Secondly, by adopting multiple optimized post-processing methods, two PRB streams with the generation rate of 0.56 Tbits/s are extracted from the two entropy sources and their randomness are verified by using NIST Special Publication 800 22 statistical tests. Through merging the two sets of 0.56 Tbits/s PRB streams by an interleaving operation, a third set of 1.12 Tbits/s PRB stream, which meets all the quality criteria of NIST statistical tests, can be further acquired. Finally, after additionally taking into account the restriction of the min entropy, the generation rate of two sets of PRB stream from the two entropy sources can still attain 0.48 Tbits/s, and then a third set of merging PRB stream is 0.96 Tbits/s. Moreover, for the sequence length of the order of 10 Gbits, the statistical bias and serial correlation coefficient of three sets of PRB streams are also analyzed. PMID- 26831981 TI - Picosecond 34 mJ pulses at kHz repetition rates from a Ho:YLF amplifier at 2 um wavelength. AB - A 2.051-um laser source delivering picosecond pulses with energies as high as 34 mJ at a 1 kHz repetition rate is reported. The main amplifier system is based on Ho:YLF and consists of a regenerative amplifier (RA) and a single-pass booster amplifier running at room temperature. The continuous-wave pumped, high-gain RA produces pulse trains with up to 10-mJ energy when operating in a stable periodic doubling regime. The recorded complete RA bifurcation diagram agrees well with our numerical simulations. At the highest pulse energy after the booster amplifier the pulse-to-pulse fluctuations are as low as 0.9% rms. Pulse compression is performed up to the 10-mJ level resulting in a duration of 37 ps. PMID- 26831982 TI - High power fiber MOPA based QCW laser delivering pulses with arbitrary duration on demand at high modulation bandwidth. AB - We report on a concept of a fiber MOPA based quasi-CW laser working at high modulation bandwidths up to 40 MHz capable of producing arbitrary pulse durations at arbitrary repetition rates. An output power of over 100 W was achieved and an on-off contrast of 25 dB. The laser features a dual-channel (dual-wavelength) seed source, a double stage YDF amplifier and a volume-Bragg-grating-based signal de-multiplexer. Minimization of transients was conducted through experiment and model analysis. PMID- 26831983 TI - High-average-power, 50-fs parametric amplifier front-end at 1.55 MUm. AB - An average-power-scalable, two-stage optical parametric chirped pulse amplifier is presented providing 90-MUJ signal pulses at 1.55 MUm and 45-MUJ idler pulses at 3.1 MUm at a repetition rate of 100 kHz. The signal pulses were recompressible to within a few percent of their ~50-fs Fourier limit in anti-reflection coated fused silica at negligible losses. The overall energy conversion efficiency from the 1030-nm pump to the recompressed signal reached 19%, significantly reducing the cost per watt of pump power compared to similar systems. The two-stage source will serve as the front-end of a three-stage system permitting the development of novel experimental strategies towards laser-based imaging of molecular structures and chemical reactivity. PMID- 26831984 TI - Optically pumped DBR-free semiconductor disk lasers. AB - We report high power distributed Bragg reflector (DBR)-free semiconductor disk lasers. With active regions lifted off and bonded to various transparent heatspreaders, the high thermal impedance and narrow bandwidth of DBRs are mitigated. For a strained InGaAs multi-quantum-well sample bonded to a single crystalline chemical-vapor deposited diamond, a maximum CW output power of 2.5 W and a record 78 nm tuning range centered at lambda~1160 nm was achieved. Laser operation using a total internal reflection geometry is also demonstrated. Furthermore, analysis for power scaling, based on thermal management, is presented. PMID- 26831985 TI - Space bandwidth product enhancement of holographic display using high-order diffraction guided by holographic optical element. AB - A space bandwidth product (SBP) enhancement method for holographic display using high-order diffraction of a spatial light modulator (SLM) is proposed. Among numerous high order diffraction terms, the plus-minus first and the zeroth are adopted and guided by holographic optical elements (HOEs) to an identical direction with the same intensity. By using a set of electro-shutters synchronized with corresponding order component, the system acts as if three SLMs are tiled in the horizontal direction. To confirm the feasibility of using HOE as the guiding optics for the system, several optical characteristics of the recording material are measured before using them. Furthermore, a computer generated hologram algorithm is proposed for compensating the wavefront distortion caused by use of the HOE. The demonstrated system achieves a three fold increase in SBP of a single SLM. The results are verified experimentally. PMID- 26831986 TI - Near-infrared broadband dual-frequency-comb spectroscopy with a resolution beyond the Fourier limit determined by the observation time window. AB - We performed broadband dual-frequency-comb spectroscopy in the near-infrared region with a much higher resolution than the Fourier limit by using discrete Fourier transforms and spectral interleaving. We observed the resonant spectrum of a Fabry-Perot cavity over a spectral range of 187 to 218 THz using this technique, and measured its free spectral ranges and finesses. The recorded spectrum includes cavity resonance lines with widths of about 2 MHz, which is much narrower than the resolution of 48 MHz determined by the observation time window. PMID- 26831987 TI - Accurate compressed look up table method for CGH in 3D holographic display. AB - Computer generated hologram (CGH) should be obtained with high accuracy and high speed in 3D holographic display, and most researches focus on the high speed. In this paper, a simple and effective computation method for CGH is proposed based on Fresnel diffraction theory and look up table. Numerical simulations and optical experiments are performed to demonstrate its feasibility. The proposed method can obtain more accurate reconstructed images with lower memory usage compared with split look up table method and compressed look up table method without sacrificing the computational speed in holograms generation, so it is called accurate compressed look up table method (AC-LUT). It is believed that AC LUT method is an effective method to calculate the CGH of 3D objects for real time 3D holographic display where the huge information data is required, and it could provide fast and accurate digital transmission in various dynamic optical fields in the future. PMID- 26831988 TI - Self-interference cancellation using dual-drive Mach-Zehnder modulator for in band full-duplex radio-over-fiber system. AB - In this paper, we design a self-interference cancellation (SIC) scheme for in band full-duplex (IBFD) radio-over-fiber (RoF) systems based on wavelength division multiplexing passive optical network (WDM-PON) architectures. By using a single dual-drive Mach-Zehnder modulator (DDMZM), over various bands up to 25 GHz, this proposed SIC system can simultaneously cancel the in-band downlink (DL) self-interference and modulate the recovered uplink (UL) radio frequency (RF) signal. OFDM-RF signals are used to study the cancellation performances of optical SIC system for the first time. Experimental results show more than 32-dB cancellation depth over 250-MHz bandwidth within 1-GHz RF band, as well as 300 MHz within 2.4-GHz and 400-MHz within 5-GHz band. As for 2.4-GHz RF band, 390.63 Mbps 16-QAM OFDM UL signal buried by strong in-band DL OFDM signal is well recovered. For broadband applications, more than 27-dB cancellation depth is achieved over 10 MHz~25 GHz wideband, so that up to 25 GHz RF band can be expanded for this IBFD WDM-RoF system. PMID- 26831989 TI - Experimental robustness of Fourier ptychography phase retrieval algorithms. AB - Fourier ptychography is a new computational microscopy technique that provides gigapixel-scale intensity and phase images with both wide field-of-view and high resolution. By capturing a stack of low-resolution images under different illumination angles, an inverse algorithm can be used to computationally reconstruct the high-resolution complex field. Here, we compare and classify multiple proposed inverse algorithms in terms of experimental robustness. We find that the main sources of error are noise, aberrations and mis-calibration (i.e. model mis-match). Using simulations and experiments, we demonstrate that the choice of cost function plays a critical role, with amplitude-based cost functions performing better than intensity-based ones. The reason for this is that Fourier ptychography datasets consist of images from both brightfield and darkfield illumination, representing a large range of measured intensities. Both noise (e.g. Poisson noise) and model mis-match errors are shown to scale with intensity. Hence, algorithms that use an appropriate cost function will be more tolerant to both noise and model mis-match. Given these insights, we propose a global Newton's method algorithm which is robust and accurate. Finally, we discuss the impact of procedures for algorithmic correction of aberrations and mis-calibration. PMID- 26831990 TI - Brillouin optical correlation domain analysis with more than 1 million effective sensing points based on differential measurement. AB - Large increase of effective sensing points in Brillouin optical correlation domain analysis (BOCDA) is achieved by simultaneously applying double modulation and optical time gate based on differential measurement scheme. The noise substructure of Brillouin gain spectrum induced by the double modulation is effectively suppressed by the differential measurement, leading to 2,000 times enlargement of the measurement range. Distributed strain and temperature sensing along a 10.5 km fiber with spatial resolution of less than 1 cm is experimentally demonstrated which corresponds to over 1 million effective sensing points. PMID- 26831991 TI - Ge microdisk with lithographically-tunable strain using CMOS-compatible process. AB - We present germanium microdisk optical resonators under a large biaxial tensile strain using a CMOS-compatible fabrication process. Biaxial tensile strain of ~0.7% is achieved by means of a stress concentration technique that allows the strain level to be customized by carefully selecting certain lithographic dimensions. The partial strain relaxation at the edges of a patterned germanium microdisk is compensated by depositing compressively stressed silicon nitride layer. Two-dimensional Raman spectroscopy measurements along with finite-element method simulations confirm a relatively homogeneous strain distribution within the final microdisk structure. Photoluminescence results show clear optical resonances due to whispering gallery modes which are in good agreement with finite-difference time-domain optical simulations. Our bandgap-customizable microdisks present a new route towards an efficient germanium light source for on chip optical interconnects. PMID- 26831992 TI - Generalized circuit model for coupled plasmonic systems. AB - We develop an analytic circuit model for coupled plasmonic dimers separated by small gaps that provides a complete account of the optical resonance wavelength. Using a suitable equivalent circuit, it shows how partially conducting links can be treated and provides quantitative agreement with both experiment and full electromagnetic simulations. The model highlights how in the conducting regime, the kinetic inductance of the linkers set the spectral blue-shifts of the coupled plasmon. PMID- 26831993 TI - Dynamics of ultra-broadband terahertz quantum cascade lasers for comb operation. AB - We present an experimental investigation of the multimode dynamics and the coherence of terahertz quantum cascade lasers emitting over a spectral bandwidth of ~1THz. The devices are studied in free-running and under direct RF modulation. Depending on the pump current we observe different regimes of operation, where RF spectra displaying single and multiple narrow beat-note signals alternate with spectra showing a single beat-note characterized by an intense phase-noise, extending over a bandwidth up to a few GHz. We investigate the relation between this phase-noise and the dynamics of the THz modes through the electro-optic sampling of the laser emission. We find that when the phase-noise is large, the laser operates in an unstable regime where the lasing modes are incoherent. Under RF modulation of the laser current such instability can be suppressed and the modes coherence recovered, while, simultaneously, generating a strong broadening of the THz emission spectrum. PMID- 26831994 TI - High-energy, sub-100 fs, all-fiber stretched-pulse mode-locked Er-doped ring laser with a highly-nonlinear resonator. AB - We report on ultra-short stretched pulse generation in an all-fiber erbium-doped ring laser with a highly-nonlinear germanosilicate fiber inside the resonator with a slightly positive net-cavity group velocity dispersion (GVD). Stable 84 fs pulses were obtained with a 12 MHz repetition rate at a central wavelength of 1560 nm with a 48.1 nm spectral pulse width (full width at half maximum, FWHM) and 30 mW average output power; this corresponds to the 29.7 kW maximum peak power and 2.5 nJ pulse energy obtained immediately from the oscillator. PMID- 26831995 TI - Distributed fiber-optic vibration sensing based on phase extraction from time gated digital OFDR. AB - A novel distributed fiber vibration sensing technique based on phase extraction from time-gated digital optical frequency domain reflectometry (TGD-OFDR) which can achieve quantitative vibration measurement with high spatial resolution and long measurement range is proposed. A 90 degree optical hybrid is used to extract phase information. By increasing frequency sweeping speed, the influence of environmental phase disturbance on TGD-OFDR is mitigated significantly, which makes phase extraction in our new scheme more reliable than that in conventional OFDR-based method, leading to the realization of long distance quantitative vibration measurement. By using the proposed technique, a distributed vibration sensor that has a measurement range of 40 km, a spatial resolution of 3.5 m, a measurable vibration frequency up to 600 Hz, and a minimal measurable vibration acceleration of 0.08g is demonstrated. PMID- 26831996 TI - Efficient dielectric metasurface collimating lenses for mid-infrared quantum cascade lasers. AB - Light emitted from single-mode semiconductor lasers generally has large divergence angles, and high numerical aperture lenses are required for beam collimation. Visible and near infrared lasers are collimated using aspheric glass or plastic lenses, yet collimation of mid-infrared quantum cascade lasers typically requires more costly aspheric lenses made of germanium, chalcogenide compounds, or other infrared-transparent materials. Here we report mid-infrared dielectric metasurface flat lenses that efficiently collimate the output beam of single-mode quantum cascade lasers. The metasurface lenses are composed of amorphous silicon posts on a flat sapphire substrate and can be fabricated at low cost using a single step conventional UV binary lithography. Mid-infrared radiation from a 4.8 MUm distributed-feedback quantum cascade laser is collimated using a polarization insensitive metasurface lens with 0.86 numerical aperture and 79% transmission efficiency. The collimated beam has a half divergence angle of 0.36 degrees and beam quality factor of M2=1.02. PMID- 26831997 TI - High resolution DAS via sinusoidal frequency scan OFDR (SFS-OFDR). AB - There are many advantages to using direct frequency modulation for OFDR based DAS. However, achieving sufficiently linear scan via direct frequency modulation is challenging and poses limits on the scan parameters. A novel method for analyzing sinusoidal frequency modulated light is presented and demonstrated for both static and dynamic sensing. SFS-OFDR projects the measured signal onto appropriate sinusoidal phase terms to obtain spatial information. Thus, by using SFS-OFDR on sinusoidal modulated light it is possible to make use of the many advantages offered by direct frequency modulation without the limitations posed by the linearity requirement. PMID- 26831998 TI - Computationally efficient autoregressive method for generating phase screens with frozen flow and turbulence in optical simulations. AB - We present a sample-based, autoregressive (AR) method for the generation and time evolution of atmospheric phase screens that is computationally efficient and uses a single parameter per Fourier mode to vary the power contained in the frozen flow and stochastic components. We address limitations of Fourier-based methods such as screen periodicity and low spatial frequency power content. Comparisons of adaptive optics (AO) simulator performance when fed AR phase screens and translating phase screens reveal significantly elevated residual closed-loop temporal power for small increases in added stochastic content at each time step, thus displaying the importance of properly modeling atmospheric "boiling". We present preliminary evidence that our model fits to AO telemetry are better reflections of real conditions than the pure frozen flow assumption. PMID- 26831999 TI - Angle- and position-insensitive electrically tunable absorption in graphene by epsilon-near-zero effect. AB - We propose an electrically tunable absorber based on epsilon-near-zero (ENZ) effect of graphene embedded in a nanocavity, which is composed of metal grating and substrate. Due to strong surface-normal electric field confined in ENZ graphene in the proposed structure, greatly enhanced light absorption (~80%) is achieved in an ultrathin graphene monolayer. By electrically controlling the Fermi-level of graphene, a sharp peak absorption wavelength is tuned over a wide range. The proposed device can work as an optical modulator or a tunable absorption filter, which has a unique feature of incident angle insensitiveness owing to the ENZ effect and magnetic dipole resonance. Moreover, existence of a significantly dominant electric field and its uniformity make the device performance independent of the position of the graphene layer in the nanocavity, which provides great fabrication tolerance. PMID- 26832000 TI - Metallic and 3D-printed dielectric helical terahertz waveguides. AB - We investigate guidance of Terahertz (THz) radiation in metallic and 3D-printed dielectric helical waveguides in the frequency range from 0.2 to 1 THz. Our experimental results obtained from THz time-domain spectroscopy (THz-TDS) measurements are in very good agreement with finite-difference time-domain (FDTD) simulations. We observe single-mode, low loss and low dispersive propagation of THz radiation in metallic helical waveguides over a broad bandwidth. The 3D printed dielectric helical waveguides have substantially extended the bandwidth of a low loss dielectric tube waveguide as observed from the experimental and simulation results. The high flexibility of the helical design allows an easy incorporation into bench top THz devices. PMID- 26832001 TI - Photocarrier dynamics in transition metal dichalcogenide alloy Mo0.5W0.5S2. AB - We report a transient absorption study of photocarrier dynamics in transition metal dichalcogenide alloy, Mo0.5W0.5S2. Photocarriers were injected by a 400-nm pump pulse and detected by a 660-nm probe pulse. We observed a fast energy relaxation process of about 0.7 ps. The photocarrier lifetime is in the range of 50 - 100 ps, which weakly depends on the injected photocarrier density and is a few times shorter than MoS2 and WS2, reflecting the relatively lower crystalline quality of the alloy. Saturable absorption was also observed in Mo0.5W0.5S2, with a saturation energy fluence of 32 MUJ cm(-2). These results provide important parameters on photocarrier properties of transition metal dichalcogenide alloys. PMID- 26832002 TI - Long period fiber grating in two-core hollow eccentric fiber. AB - Long period fiber gratings (LPGs) in a two-core hollow eccentric fiber (TCHF) have been demonstrated experimentally. Two LPGs have been fabricated into the respective core of the TCHF by a high frequency CO2 laser. The coupling characteristics in the TCHF-LPG have been studied using the coupling mode theory (CMT). The resonant peak is mainly caused by the coupling between the core mode LP01 and cladding mode LP81. The experimental results agree well with the simulation results. Furthermore, the sensing properties of the TCHF-LPG have been investigated with respect to bending, temperature and axial strain. Compared with the LPG in the single mode fiber (SMF), the experimental results indicate that the sensitivity of the TCHF-LPGs to bending curvature is low and even very small at some bending directions. In addition, TCHF-LPGs are insensitive to the axial strain while sensitive to the temperature. Therefore, the proposed TCHF-LPGs can efficiently sense the changing temperature that is independent of the strain. Moreover, the TCHF-LPGs can also be applied to two-channel filters without signal crosstalk between two cores. PMID- 26832003 TI - Stable and near Fourier-transform-limit 30fs pulse compression with a tiled grating compressor scheme. AB - The fabrication of meter-sized-gratings limits the rapid development of worldwide femtosecond ultra-intense lasers with 10PW or higher peak power, and the grating tiling method is an alternative to this problem. But the unreliability and complexity of the traditional grating tiling, which has already been widely used in picosecond Petawatt lasers, challenges its application in femtosecond ultra intense lasers for wider bandwidth and more sensitive grating attitude. In this paper, we demonstrate an experiment to compress an 800nm centered nanosecond deep chirped-pulse to around 30fs by an object-image-grating self-tiling compressor, to the best of our knowledge, which is the shortest pulse compressed by a tiled grating compressor. Both the compression pulse and the focal spot are stable and close to the theoretical limits. We believe it is a feasible solution to the grating-size-limited problem for recent femtosecond 10PW Ti:sapphire or OPCPA laser projects. PMID- 26832004 TI - Ultrafast high-repetition imaging of fuel sprays using picosecond fiber laser. AB - Modern diesel injectors operate at very high injection pressures of about 2000 bar resulting in injection velocities as high as 700 m/s near the nozzle outlet. In order to better predict the behavior of the atomization process at such high pressures, high-resolution spray images at high repetition rates must be recorded. However, due to extremely high velocity in the near-nozzle region, high speed cameras fail to avoid blurring of the structures in the spray images due to their exposure time. Ultrafast imaging featuring ultra-short laser pulses to freeze the motion of the spray appears as an well suited solution to overcome this limitation. However, most commercial high-energy ultrafast sources are limited to a few kHz repetition rates. In the present work, we report the development of a custom-designed picosecond fiber laser generating ~ 20 ps pulses with an average power of 2.5 W at a repetition rate of 8.2 MHz, suitable for high speed imaging of high-pressure fuel jets. This fiber source has been proof tested by obtaining backlight images of diesel sprays issued from a single-orifice injector at an injection pressure of 300 bar. We observed a consequent improvement in terms of image resolution compared to standard white-light illumination. In addition, the compactness and stability against perturbations of our fiber laser system makes it particularly suitable for harsh experimental conditions. PMID- 26832005 TI - Single-shot volumetric laser induced fluorescence (VLIF) measurements in turbulent flows seeded with iodine. AB - This work reports the experimental demonstration of single-shot visualization of turbulent flows in all three spatial dimensions (3D) based on volumetric laser induced fluorescence (VLIF). The measurements were performed based on the LIF signal of iodine (I2) vapor seeded in the flow. In contrast to established planar LIF (PLIF) technique, the VLIF technique excited the seeded I2 vapor volumetrically by a thick laser slab. The volumetric LIF signals emitted were then simultaneously collected by a total of five cameras from five different orientations, based on which a 3D tomographic reconstruction was performed to obtain the 3D distribution of the I2 vapor in the target flow. Single-shot measurements (with a measurement duration of a few ns) were demonstrated in a 50 mm * 50 mm * 50 mm volume with a nominal spatial resolution of 0.42 mm and an actual resolution of ~0.71 mm in all three dimensions (corresponding to a total of 120 * 120 * 120 voxels). PMID- 26832006 TI - Micropatterned luminescent optical epoxies. AB - We study the fabrication and optical properties of micropatterned luminescent optical epoxy samples. Five different photoluminescent materials were added to epoxy resin to form luminescent epoxies of different colors and micropatterned gratings were imprinted on the surface of the samples. The absorbance spectra of the unpatterned epoxy samples were measured with spectrometer and the luminescence intensities of all samples were measured using custom made bispectrometer. The methods used in this work offer an efficient and straightforward way to produce micro- or nanopatterned luminescent optical epoxies for various applications, such as LED coatings and solar concentrators. PMID- 26832007 TI - Phase-sensitive fiber-based parametric all-optical switch. AB - We experimentally demonstrate, for the first time, an all-optical switch in a phase-sensitive fiber optic parametric amplifier operated in saturation. We study the effect of phase variation of the signal and idler waves on the pump power depletion. By changing the phase of a 0.9 mW signal/idler pair wave by pi/2 rad, a pump power extinction ratio of 30.4 dB is achieved. Static and dynamic characterizations are also performed and time domain results presented. PMID- 26832008 TI - Free-space quantum key distribution to a moving receiver. AB - Technological realities limit terrestrial quantum key distribution (QKD) to single-link distances of a few hundred kilometers. One promising avenue for global-scale quantum communication networks is to use low-Earth-orbit satellites. Here we report the first demonstration of QKD from a stationary transmitter to a receiver platform traveling at an angular speed equivalent to a 600 km altitude satellite, located on a moving truck. We overcome the challenges of actively correcting beam pointing, photon polarization and time-of-flight. Our system generates an asymptotic secure key at 40 bits/s. PMID- 26832009 TI - Experimental investigations into capability of terahertz surface plasmons to bridge macroscopic air gaps. AB - Results of experimental and theoretical studies of the capability of terahertz surface plasmons (SPs) to cross macroscopic air gaps in a substrate (or between substrates) with admissible losses are presented. SPs were launched with quasi-cw free-electron laser radiation with 130 MUm wavelength (lambda). We managed to detect SPs passing across gaps as wide as 100 mm (or about 10(3)?lambda), which is very promising for development of terahertz SP circuitry. The phenomenon was harnessed for splitting an SP beam into two new ones, guided by their own individual plane-surface substrates. PMID- 26832010 TI - Intracavity-pumped, cascaded AgGaSe2 optical parametric oscillator tunable from 5.8 to 18 um. AB - A AgGaSe2 nonlinear crystal placed in a coupled cavity is intracavity pumped by the ~1.85-um signal pulses of a 1.064-um pumped Rb:PPKTP doubly-resonant optical parametric oscillator (OPO) operating at a repetition rate of 100 Hz. Using two samples cut for type-I and II phase-matching, the overall idler tunability of the singly-resonant AgGeSe2 OPO covers an unprecedented spectral range from 5.8 to ~18 um in the mid-IR. PMID- 26832011 TI - Second-harmonic scanning microscopy of domains in Al wire bonds in IGBT modules. AB - Scanning second harmonic generation microscopy has been used to investigate crystallographic orientation of the grain structure in Al wire bonds in insulated gate bipolar transistor modules. It was shown that the recorded second harmonic microscopy images revealed the grain structure of the Al sample. Additional information of the individual grain orientation was achieved by using simple interpretations of the recorded rotational anisotropy. PMID- 26832012 TI - Efficient analysis of deep high-index-contrast gratings under arbitrary illumination. AB - An efficient method for computing the problem of an electromagnetic beam transmission through deep periodic dielectric gratings is presented. In this method the beam is decomposed into a spectrum of plane waves, transmission coefficients corresponding to each such plane wave are found via Rigorous Coupled Wave Analysis, and the transmitted beam is calculated via inverse Fourier integral. To make the approach efficient for deep gratings the fast variations of the transmission coefficients versus spatial frequency are accounted for analytically by casting the summations and integrals in a form that has explicit rapidly varying exponential terms. The resulting formulation allows computing the transmitted beam with a small number of samples independent of the grating depth. PMID- 26832013 TI - Q-factor analysis of nonlinear impairments in ultrahigh-speed Nyquist pulse transmission. AB - We present detailed analytical and numerical results of the dispersion and nonlinear tolerances of RZ and Nyquist optical pulses in ultrahigh-speed TDM transmissions. From a Q-map analysis, i.e. by numerically calculating the Q factor distribution as a function of transmission power and fiber dispersion, we found that Nyquist TDM transmission has a substantially larger Q margin as regards both dispersion and optical power thanks to ISI-free overlapped TDM. We also show that the optimum transmission power for Nyquist pulses is 2 dB lower than for RZ pulses. An analytical model is provided to explain the overlap induced nonlinear impairments in Nyquist TDM transmission in a high power regime, which agrees well with numerical results. PMID- 26832014 TI - Parallelized multichannel BSDF measurements. AB - The intensity of scattered light is extremely sensitive to even small changes of illumination wavelength, incident angle, polarization states, or even the measurement position. To obtain light scattering distributions with varied parameters, time-consuming sequential measurement procedures are typically employed. Here, we propose a concept for the measurement of multiple properties at the same time. This is achieved by tailoring orthogonal frequency division multiplexing (OFDM) for light scattering measurement techniques to the required low inter-channel crosstalk performance. The concept is used for a highly-robust roughness and contamination characterization, to derive one-shot roughness information, as well as to characterize color and appearance. PMID- 26832015 TI - Sub-Rayleigh-diffraction imaging via modulating classical light. AB - The spatial resolution of a traditional imaging system is restricted by the Rayleigh diffraction limit. In this paper, two types of classical light sources are generated by modulating the amplitude distribution and wavefront of a laser beam randomly, and the generated light sources can exhibit the features of the superposition of two-photon Fock states and the incoherent mixture of two-photon Fock states, respectively. With the generated light sources, the two-fold coherent and incoherent imaging schemes can be achieved, which lead to spatial resolution enhancement, and exceed the Rayleigh diffraction limit in the imaging system. PMID- 26832016 TI - Improving target discrimination ability of active polarization imagers by spectral broadening. AB - Active polarization imagers using liquid crystal variable retarders (LCVR) usually operate at one given wavelength for the sake of polarimetric accuracy. However, this often requires to use narrowband filters which reduces the amount of light entering the system and thus the signal-to-noise ratio. For applications where good target/background discriminability (contrast) is required rather than polarimetric accuracy, this may not be the best choice. In this Article, we address contrast optimization in the case of broadband active polarimetric imaging for target detection applications. Through numerical and experimental studies, we show that broadening the spectrum of the light entering the system can increase the contrast between two regions of a scene. Furthermore, we show that this contrast can be further increased by taking into account the spectral dependence of the scene and of the polarimetric properties of the imaging system in the optimization of the measurement procedure. PMID- 26832017 TI - Automatic measurement of wood fiber orientation and knot detection using an optical system based on heating conduction. AB - In this paper, a new approach to computing the deviation of wood grain is proposed. To do this, the thermal conduction properties of timber are used (higher conduction in the fiber direction). Exciting the surface of the wood with a laser and capturing the thermal conduction using a thermal camera, an ellipse can be observed. Using a method similar to the tracheid effect, it is possible to extract information from this ellipse, such as the slope of grain and the presence of knots. With this method it is therefore possible to extend the mechanical model (assessing the mechanical properties of timber) to take certain singularities into account. Using this approach, the slope of grain can be estimated for any wood species, either hardwood or softwood, which was not possible with the existing tracheid effect. PMID- 26832018 TI - Femtosecond laser-written high-efficiency blazed phase gratings in the volume of soda lime glass for light management in solar modules. AB - Highly efficient volume phase gratings have been fabricated in low-iron soda lime glass using femtosecond (fs) laser pulses with 1030 nm wavelength and 270 fs pulse duration. Optical simulations based on rigorous coupled-wave analysis theory were performed to determine optimal grating parameters and designs for the application of the gratings for light management in solar modules, suggesting a very effective blazed-like design. Several of such blazed phase gratings have been fabricated and analyzed by measuring their diffraction efficiencies into first and higher orders. Up to 77% of the incoming light in the wavelength region relevant for silicon-based photovoltaics were diffracted by these gratings. Typical induced refractive index changes between 0.002 and 0.006 were derived by comparing the experimental efficiencies with the simulation results. PMID- 26832019 TI - Transmission optical coherence tomography based measurement of optical material properties. AB - We present transmission optical coherence tomography (transmission OCT) as a versatile tool to measure optical material properties of turbid media. The transmission OCT signal is described in detail and it is demonstrated how the group refractive index (n(g)), group velocity dispersion (GVD) and optical attenuation can be determined from this signal. We experimentally validate the refractive index properties of glasses, liquids and glucose water solutions in terms of n(g) and GVD. Measurements of scattering coefficients are determined using transmission OCT for suspensions of silica particles. Quantitative agreement is obtained with a dependent scattering model, both for the average as well as the wavenumber resolved optical attenuation coefficient. Good agreement is observed between our measurements and literature values. PMID- 26832020 TI - Generation of circularly polarized high harmonic radiation using a transmission multilayer quarter waveplate. AB - High harmonic radiation is meanwhile nearly extensively used for the spectroscopic investigation of electron dynamics with ultimate time resolution. The majority of high harmonic beamlines provide linearly polarized radiation created in a gas target. However, circular polarization greatly extends the spectroscopic possibilities for high harmonics, especially in the analysis of samples with chirality or prominent spin polarization. We produced a free standing multilayer foil as a transmission EUV quarter waveplate and applied it for the first time to high harmonic radiation. We measured a broadband (4.6 eV FWHM) ellipticity of 75% at 66 eV photon energy with a transmission efficiency of 5%. The helicity is switchable and the ellipticity can be adjusted to lower values by angle tuning. As a single element it can be easily integrated in any existing harmonic beamline without major changes. PMID- 26832021 TI - Microwave photonic bandstop filter with wide tunability and adjustable bandwidth. AB - A microwave photonic bandstop filter is proposed and experimentally demonstrated in this work. The filter exhibits promising performance combination of reconfigurability, frequency tunability, and bandwidth adjustment. The phase modulation on two orthogonal polarization states produces a bandpass and a lowpass MPF, respectively. The key concept of destructive interference between the bandpass and lowpass MPF enables the reconfiguration of MPF from bandpass to bandstop. By adjusting the wavelength of two orthogonally polarized optical carriers and the bandwidth of an optical bandpass filter, the bandstop filter is tunable in terms of center frequency and bandwidth. PMID- 26832022 TI - Free-space beam shaping for precise control and conversion of modes in optical fiber: errata. AB - We correct a few typographical errors in the original manuscript. PMID- 26832023 TI - Temperature effects of Mach-Zehnder interferometer using a liquid crystal-filled fiber. AB - We demonstrated a simple and cost-effective method to fabricate all fiber Mach Zehnder interferometer (MZI) based on cascading a short section of liquid crystal (LC)-filled hollow-optic fiber (HOF) between two single mode fibers by using automatically splicing technique. The transmission spectra of the proposed MZI with different LC-infiltrated length were measured and the temperature-induced wavelength shifts of the interference fringes were recorded. Both blue shift and red shift were observed, depending the temperature range. Based on our experimental results, interference fringe was observed with a maximum interferometric contrast over 35dB. The temperature-induced resonant wavelength blue-shifts 70.4 nm for the MZI with an LC length of 9.79 mm and the wavelength temperature sensitivity of -1.55 nm/ degrees C is easily achieved as the temperature increases from 25 degrees C to 77 degrees C. PMID- 26832024 TI - Absolute group refractive index measurement of air by dispersive interferometry using frequency comb. AB - The absolute group refractive index of air at 1563 nm is measured by dispersive interferometry, and a combined uncertainty of 1.2 * 10(-8) is achieved. The group refractive index of air is calculated from the dispersive interferograms of the two beams passing through the inner and outer regions of a vacuum cell by fast Fourier-transform. Experimental results show that the discrepancies between our method and modified Edlen equation are less than 3.43 * 10(-8) and 4.4 * 10(-8) for short-term and long-term experiments, respectively. The interferogram update rate is 15 ms, which makes it suitable for application of real-time monitoring. Furthermore, it is promising to improve the measurement uncertainty to 3.0 * 10( 9) by changing the material of the vacuum cell and measuring its length more accurately through optical interferometry. PMID- 26832025 TI - Mode-resolved Fabry-Perot experiment in low-loss Bragg-reflection waveguides. AB - Based on the interaction between different spatial modes, semiconductor Bragg reflection waveguides (BRWs) provide a highly functional platform for non-linear optics. For achieving any desired quantum optical functionality, we must control and engineer the properties of each spatial mode. To reach this purpose we extend the Fabry-Perot technique and achieve a detailed linear optical characterization of dispersive multimode semiconductor waveguides. With this efficient broadband spectral method we gain direct experimental access to the relevant modes of our BRWs and determine their group velocities. Furthermore, we show that our waveguides have lower than expected loss coefficients. This renders them suitable for integrated quantum optics applications. PMID- 26832026 TI - Optimal geometry of nonlinear silicon slot waveguides accounting for the effect of waveguide losses. AB - The optimal geometry of silicon-organic hybrid slot waveguides is investigated in the context of the efficiency of four-wave mixing (FWM), a chi(3) nonlinear optical process. We study the effect of slot and waveguide widths, as well as waveguide asymmetry on the two-photon absorption (TPA) figure of merit and the roughness scattering loss. The optimal waveguide core width is shown to be 220nm (symmetric) with a slot width of 120nm, at a fixed waveguide height of 220nm. We also show that state-of-the-art slot waveguides can outperform rib waveguides, especially at high powers, due to the high TPA figure-of-merit. PMID- 26832027 TI - Silicon-integrated short-wavelength hybrid-cavity VCSEL. AB - We demonstrate a short-wavelength hybrid-cavity vertical-cavity surface-emitting laser (VCSEL) heterogeneously integrated on silicon. A GaAs-based "half-VCSEL" has been attached to a dielectric distributed Bragg reflector (DBR) on a silicon wafer using ultra-thin divinylsiloxane-bis-benzocyclobutene (DVS-BCB) adhesive bonding, thereby creating a cavity with the standing-wave optical field extending over the silicon- and GaAs-based parts of the cavity. A 9 um oxide aperture diameter VCSEL with a threshold current of 1.2 mA produces 1.6 mW optical output power at 6.0 mA bias current with a wavelength of ~845 nm. PMID- 26832028 TI - Narrowing of the linewidth of an optical parametric oscillator by an acousto optic modulator for the realization of mid-IR noise-immune cavity-enhanced optical heterodyne molecular spectrometry down to 10-10 cm-1 Hz-1/2. AB - The linewidth of a singly resonant optical parametric oscillator (OPO) has been narrowed with respect to an external cavity by the use of an acousto-optic modulator (AOM). This made possible an improvement of the sensitivity of a previously realized OPO-based noise-immune cavity-enhanced optical heterodyne molecular spectrometry instrument for the 3.2 - 3.9 um mid-infrared region by one order of magnitude. The resulting system shows a detection sensitivity for methane of 2.4 * 10(-10) cm(-1) Hz(-1/2) and 1.3 * 10(-10) cm(-1) at 20 s, which allows for detection of both the environmentally important (13)CH(4) and CH(3)D isotopologues in atmospheric samples. PMID- 26832029 TI - 4-Gbit/s visible light communication link based on 16-QAM OFDM transmission over remote phosphor-film converted white light by using blue laser diode. AB - Visible Light Communication (VLC) as a new technology for ultrahigh-speed communication is still limited when using slow modulation light-emitting diode (LED). Alternatively, we present a 4-Gbit/s VLC system using coherent blue-laser diode (LD) via 16-quadrature amplitude modulation orthogonal frequency division multiplexing. By changing the composition and the optical-configuration of a remote phosphor-film the generated white light is tuned from cool day to neutral, and the bit error rate is optimized from 1.9 * 10(-2) to 2.8 * 10(-5) in a blue filter-free link due to enhanced blue light transmission in forward direction. Briefly, blue-LD is an alternative to LED for generating white light and boosting the data rate of VLC. PMID- 26832030 TI - Dynamic two-dimensional refractive index modulation for high performance acousto optic deflector. AB - The performance of an acousto-optic deflector is studied for two-dimensional refractive index that varies as periodic and sinc functions in the transverse and longitudinal directions, respectively, with respect to the direction of light propagation. Phased array piezoelectric transducers can be operated at different phase shifts to produce a two-dimensionally inhomogeneous domain of phase grating in the acousto-optic media. Also this domain can be steered at different angles by selecting the phase shift appropriately. This mechanism of dynamically tilting the refractive index-modulated domain enables adjusting the incident angle of light on the phase grating plane without moving the light source. So the Bragg angle of incidence can be always achieved at any acoustic frequency, and consequently, the deflector can operate under the Bragg diffraction condition at the optimum diffraction efficiency. Analytic solutions are obtained for the Bragg diffraction of plane waves based on the second order coupled mode theory, and the diffraction efficiency is found to be unity for optimal index modulations at certain acoustic parameters. PMID- 26832031 TI - Graphene based resonance structure to enhance the optical pressure between two planar surfaces. AB - To enhance the optical pressure on a thin dielectric sample, a resonance structure using graphene layers coated over a metal film on a high index prism sputtered with MgF2 was theoretically analyzed. The number of graphene layers and the thicknesses of metal and MgF2 films were optimized to achieve the highest optical pressure on the sample. Effects of three different types of metals on the optical pressure were investigated numerically. In addition, simulations were carried out for samples with various thicknesses. Our numerical results show that the optical pressure increased by more than five orders of magnitude compared to the conventional metal-film-base resonance structure. The highest optical pressure was obtained for 10 layers of graphene deposited on 29-nm thick Au film and 650 nm thickness of MgF2 at 633nm wavelength, The proposed graphene based resonance structure can open new possibilities for optical tweezers, nanomechnical devices and surface plasmon based sensing and imaging techniques. PMID- 26832032 TI - Polarization instability of Raman solitons ejected during supercontinuum generation. AB - We numerically investigate polarization instability of soliton fission and the polarization dynamics of Raman solitons ejected during supercontinuum generation in a photonics crystal fiber using the coupled vector generalized nonlinear Schrodinger equations for both linear and circular birefringent fibers. The evolution of the state of polarizations of the ejected Raman soliton as representated on the Poincare sphere is affected by both nonlinear and linear polarization rotations on the Poincare sphere. The polarization dynamics reveal the presence of a polarization separatrix and the emergence of stable slow and unstable fast eigen-polarizations for the Raman solitons ejected in the supercontinuum generation process. Circularly birefringent fiber is investigated and found to simplify the nonlinear polarization dynamics. PMID- 26832033 TI - Adaptive optics correction into single mode fiber for a low Earth orbiting space to ground optical communication link using the OPALS downlink. AB - An adaptive optics (AO) testbed was integrated to the Optical PAyload for Lasercomm Science (OPALS) ground station telescope at the Optical Communications Telescope Laboratory (OCTL) as part of the free space laser communications experiment with the flight system on board the International Space Station (ISS). Atmospheric turbulence induced aberrations on the optical downlink were adaptively corrected during an overflight of the ISS so that the transmitted laser signal could be efficiently coupled into a single mode fiber continuously. A stable output Strehl ratio of around 0.6 was demonstrated along with the recovery of a 50 Mbps encoded high definition (HD) video transmission from the ISS at the output of the single mode fiber. This proof of concept demonstration validates multi-Gbps optical downlinks from fast slewing low-Earth orbiting (LEO) spacecraft to ground assets in a manner that potentially allows seamless space to ground connectivity for future high data-rates network. PMID- 26832034 TI - Multi-exposure color imaging with stacked thin-film luminescent concentrators. AB - We present a fully transparent, scalable, and flexible color image sensor that consists of stacked thin-film luminescent concentrators (LCs). At each layer, it measures a Radon transform of the corresponding LC's spectral responses. Color images are then reconstructed through inverse Radon transforms that are obtained using machine learning. A high sampling rate in Radon space allows encoding multiple exposures to cope with under- and overexposed cases in one recording. Thus, our sensor simultaneously measures multiple spectral responses in different LC layers and multiple exposures in different Radon coefficients per layer. We also show that machine learning enables adequate three-channel image reconstruction from the response of only two LC layers. PMID- 26832035 TI - 850-nm hybrid fiber/free-space optical communications using orbital angular momentum modes. AB - Light beams can carry orbital angular momentum (OAM) associated to the helicity of their phasefronts. These OAM modes can be employed to encode information onto a laser beam for transmitting not only in a fiber link but also in a free-space optical (FSO) one. Regarding this latter scenario, FSO communications are considered as an alternative and promising mean complementing the traditional optical communications in many applications where the use of fiber cable is not justified. This next generation FSO communication systems have attracted much interest recently, and the inclusion of beams carrying OAM modes can be seen as an efficient solution to increase the capacity and the security in the link. In this paper, we discuss an experimental demonstration of a proposal for next generation FSO communication system where a light beam carrying different OAM modes and affected by M turbulence is coupled to the multimode fiber link. In addition, we report a better and more robust behavior of higher order OAM modes when the intermodal dispersion is dominant in the fiber after exceeding its maximum range of operation. PMID- 26832036 TI - Phase matching in hyperbolic wire media for nonlinear frequency conversion. AB - Efficient nonlinear frequency conversion requires a phase matching condition to be satisfied. We analyze the dispersion of the modes of hyperbolic wire metamaterials and demonstrate that phase matching at infrared wavelengths can be achieved with a variety of constituent materials, such as GaAs, in which phase matching cannot easily be achieved by conventional means. Our finding promises access to many materials with attractive nonlinear properties. PMID- 26832037 TI - Generation and excitation of different orbital angular momentum states in a tunable microstructure optical fiber. AB - A tunable microstructure optical fiber for different orbital angular momentum states generation is proposed and investigated by simulation. The microstructure optical fiber is composed of a high refractive index ring and a hollow core surrounded by four small air holes. The background material of the microstructure fiber is pure silica. The hollow core and the surrounded four small air holes are infiltrated by optical functional material whose refractive index can be modulated via physical parameters, leading to the conversion between circular polarized fundamental mode and different orbital angular momentum states at tunable operating wavelengths. A theoretical model is established and the coupling mechanism is systematically analyzed and investigated based on coupled mode theory. The fiber length can be designed specifically to reach the maximum coupling efficiency for every OAM mode respectively, and can also be fixed at a certain value for several OAM modes generation under tunable refractive index conditions. The proposed fiber coupler is flexible and compact, making it a good candidate for tunable OAM generation and sensing systems. PMID- 26832038 TI - Imaging model for the scintillator and its application to digital radiography image enhancement. AB - Digital Radiography (DR) images obtained by OCD-based (optical coupling detector) Micro-CT system usually suffer from low contrast. In this paper, a mathematical model is proposed to describe the image formation process in scintillator. By solving the correlative inverse problem, the quality of DR images is improved, i.e. higher contrast and spatial resolution. By analyzing the radiative transfer process of visible light in scintillator, scattering is recognized as the main factor leading to low contrast. Moreover, involved blurring effect is also concerned and described as point spread function (PSF). Based on these physical processes, the scintillator imaging model is then established. When solving the inverse problem, pre-correction to the intensity of x-rays, dark channel prior based haze removing technique, and an effective blind deblurring approach are employed. Experiments on a variety of DR images show that the proposed approach could improve the contrast of DR images dramatically as well as eliminate the blurring vision effectively. Compared with traditional contrast enhancement methods, such as CLAHE, our method could preserve the relative absorption values well. PMID- 26832039 TI - Fill-factor improvement of Si CMOS single-photon avalanche diode detector arrays by integration of diffractive microlens arrays. AB - Single-photon avalanche diode (SPAD) detector arrays generally suffer from having a low fill-factor, in which the photo-sensitive area of each pixel is small compared to the overall area of the pixel. This paper describes the integration of different configurations of high efficiency diffractive optical microlens arrays onto a 32 * 32 SPAD array, fabricated using a 0.35 um CMOS technology process. The characterization of SPAD arrays with integrated microlens arrays is reported over the spectral range of 500-900 nm, and a range of f-numbers from f/2 to f/22. We report an average concentration factor of 15 measured for the entire SPAD array with integrated microlens array. The integrated SPAD and microlens array demonstrated a very high uniformity in overall efficiency. PMID- 26832040 TI - High-efficiency superconducting nanowire single-photon detectors fabricated from MoSi thin-films. AB - We report on MoSi SNSPDs which achieved high system detection efficiency (87.1 +/ 0.5% at 1542 nm) at 0.7 K and we demonstrate that these detectors can also be operated with saturated internal efficiency at a temperature of 2.3 K in a Gifford-McMahon cryocooler. We measured a minimum system jitter of 76 ps, maximum count rate approaching 10 MHz, and polarization dependence as low as 3.3 +/- 0.1%. The performance of MoSi SNSPDs at 2.3 K is similar to the performance of WSi SNSPDs at < 1 K. The higher operating temperature of MoSi SNSPDs makes these devices promising for widespread use due to the simpler and less expensive cryogenics required for their operation. PMID- 26832041 TI - Edge detection based on gradient ghost imaging. AB - We present an experimental demonstration of edge detection based on ghost imaging (GI) in the gradient domain. Through modification of a random light field, gradient GI (GGI) can directly give the edge of an object without needing the original image. As edges of real objects are usually sparser than the original objects, the signal-to-noise ratio (SNR) of the edge detection result will be dramatically enhanced, especially for large-area, high-transmittance objects. In this study, we experimentally perform one- and two-dimensional edge detection with a double-slit based on GI and GGI. The use of GGI improves the SNR significantly in both cases. Gray-scale objects are also studied by the use of simulation. The special advantages of GI will make the edge detection based on GGI be valuable in real applications. PMID- 26832042 TI - Elementary signals in ptychography. AB - Ptychographic imaging has gained popularity for its high resolving power and sensitivity as well as for its ability to map simultaneously the sample's complex valued refractive index and the illumination. Yet, despite significant progress that allows for reliable practical implementation, some of the technique's fundamentals remain poorly understood, and oftentimes successful data acquisition is either overly conservative or relies more on experimenters experience than on rational data acquisition strategies. Here, we propose a theoretical framework of ptychography, which is based on Gabor's notion of decomposition into elementary signals and the concept of frames. We demonstrate how this framework can straightforwardly be used to derive sampling requirements or to provide arguments on how to optimize the ptychographic scan. More generally, our theoretical framework can serve as a bridge between the experimental technique and the rich and well established mathematical disciplines of wavelets decomposition and spectrogram analysis. PMID- 26832043 TI - Nonlinear optimization approach for Fourier ptychographic microscopy. AB - Fourier ptychographic microscopy (FPM) is recently proposed as a computational imaging method to bypass the limitation of the space-bandwidth product of the traditional optical system. It employs a sequence of low-resolution images captured under angularly varying illumination and applies the phase retrieval algorithm to iteratively reconstruct a wide-field, high-resolution image. In current FPM imaging system, system uncertainties, such as the pupil aberration of the employed optics, may significantly degrade the quality of the reconstruction. In this paper, we develop and test a nonlinear optimization algorithm to improve the robustness of the FPM imaging system by simultaneously considering the reconstruction and the system imperfections. Analytical expressions for the gradient of a squared-error metric with respect to the object and illumination allow joint optimization of the object and system parameters. The algorithm achieves superior reconstructions when the system parameters are inaccurately known or in the presence of noise and corrects the pupil aberrations simultaneously. Experiments on both synthetic and real captured data validate the effectiveness of the proposed method. PMID- 26832044 TI - Experimental study on merits of virtual cleaning of paintings with aged varnish. AB - To assess the accuracy of virtual cleaning of Old Master paintings (i.e. digital removal of discolored varnishes), a physical model was developed and experimentally tested using reflectance imaging spectroscopy on three paintings undergoing conservation treatment. The model predicts the reflectance spectra of the painting without varnish or after application of a new varnish from the reflectances of the painting with the aged varnish, given the absorption of the aged varnish and the scattering terms. The resulting color differences between the painting actually and virtually cleaned can approach the perceivable limit. Residual discrepancies are ascribable to spatial variations in the characteristics of the aged varnish (scattering, optical thickness) and the exposed painting (surface roughness). PMID- 26832045 TI - Axicons for mode conversion in high peak power, higher-order mode, fiber amplifiers. AB - Higher-order mode fiber amplifiers have demonstrated effective areas as large as 6000 MUm2, allowing for high pulse energy and peak power amplification. Long period gratings are used to convert the fundamental mode to the higher-order mode at the entrance to the amplifier, and reconvert back to the fundamental at the exit, to achieve a diffraction limited beam. However, long period gratings are susceptible to nonlinearity at high peak power. In this work, we propose and demonstrate axicons for linear bulk-optic mode conversion at the output of higher order mode amplifiers. We achieve an M2 of less than 1.25 for 80% mode conversion efficiency. Experiments with pulsed amplifiers confirm that the mode conversion is free from nonlinearity. Furthermore, chirp pulse amplifier experiments confirm that HOM amplifiers plus axicon mode convertors provide energy scalability in femtosecond pulses, compared to smaller effective area, fundamental mode fiber amplifiers. We also propose and demonstrate a route towards fiber integration of the axicon mode convertor by fabricating axicons directly on the tip of the fiber amplifier end-cap. PMID- 26832046 TI - Study of temperature distributions in pc-WLEDs with different phosphor packages. AB - Phosphor converted white LEDs (pc-WLED) with different geometries, namely remote dome, remote-plate, half-dome, and conformal-coating packages, were studied using simulations to obtain the thermal power and the temperature distribution. The results of an experiment carried out to measure the temperature distribution in these pc-WLEDs validate the simulation results. A hotspot always occurs in the phosphor region. The conformal-coating package is the most feasible choice to reduce the hotspot temperature comparing with the other geometries. PMID- 26832047 TI - Mobile multi-wavelength polarization Raman lidar for water vapor, cloud and aerosol measurement. AB - Aiming at the detection of atmospheric water vapor mixing ratio, depolarization ratio, backscatter coefficient, extinction coefficient and cloud information, the Water vapor, Cloud and Aerosol Lidar (WACAL) is developed by the lidar group at Ocean University of China. The lidar consists of transmitter, receiver, data acquisition and auxiliary system. For the measurement of various atmospheric physical properties, three channels including Raman channel, polarization channel and infrared channel are integrated in WACAL. The integration and working principle of these channels are introduced in details. The optical setup, the housekeeping of the system and the data retrieval routines are also presented. After the completion of the construction of the lidar, the WACAL system was installed in Ocean University of China (36.165 degrees N, 120.5 degrees E), Qingdao for the measurement of atmosphere during 2013 and 2014. The measurement principles and some case studies corresponding to various atmospheric physical properties are provided. Finally, the result of one continuous measurement example operated on 13 June 2014 is presented. The WACAL can measure the aerosol and cloud optical properties as well as the water vapor mixing ratio. It is useful for studying the direct and indirect effects of the aerosol on the climate change. PMID- 26832048 TI - Continuous shading and its fast update in fully analytic triangular-mesh-based computer generated hologram. AB - Fully analytic mesh-based computer generated hologram enables efficient and precise representation of three-dimensional scene. Conventional method assigns uniform amplitude inside individual mesh, resulting in reconstruction of the three-dimensional scene of flat shading. In this paper, we report an extension of the conventional method to achieve the continuous shading where the amplitude in each mesh is continuously varying. The proposed method enables the continuous shading, while maintaining fully analytic framework of the conventional method without any sacrifice in the precision. The proposed method can also be extended to enable fast update of the shading for different illumination directions and the ambient-diffuse reflection ratio based on Phong reflection model. The feasibility of the proposed method is confirmed by the numerical and optical reconstruction of the generated hologram. PMID- 26832049 TI - Speckle-learning-based object recognition through scattering media. AB - We experimentally demonstrated object recognition through scattering media based on direct machine learning of a number of speckle intensity images. In the experiments, speckle intensity images of amplitude or phase objects on a spatial light modulator between scattering plates were captured by a camera. We used the support vector machine for binary classification of the captured speckle intensity images of face and non-face data. The experimental results showed that speckles are sufficient for machine learning. PMID- 26832050 TI - Underwater depth imaging using time-correlated single-photon counting. AB - A depth imaging system, based on the time-of-flight approach and the time correlated single-photon counting (TCSPC) technique, was investigated for use in highly scattering underwater environments. The system comprised a pulsed supercontinuum laser source, a monostatic scanning transceiver, with a silicon single-photon avalanche diode (SPAD) used for detection of the returned optical signal. Depth images were acquired in the laboratory at stand-off distances of up to 8 attenuation lengths, using per-pixel acquisition times in the range 0.5 to 100 ms, at average optical powers in the range 0.8 nW to 950 MUW. In parallel, a LiDAR model was developed and validated using experimental data. The model can be used to estimate the performance of the system under a variety of scattering conditions and system parameters. PMID- 26832051 TI - Cascaded optical fiber link using the internet network for remote clocks comparison. AB - We report a cascaded optical link of 1100 km for ultra-stable frequency distribution over an Internet fiber network. The link is composed of four spans for which the propagation noise is actively compensated. The robustness and the performance of the link are ensured by five fully automated optoelectronic stations, two of them at the link ends, and three deployed on the field and connecting the spans. This device coherently regenerates the optical signal with the heterodyne optical phase locking of a low-noise laser diode. Optical detection of the beat-note signals for the laser lock and the link noise compensation are obtained with stable and low-noise fibered optical interferometer. We show 3.5 days of continuous operation of the noise-compensated 4-span cascaded link leading to fractional frequency instability of 4x10(-16) at 1-s measurement time and 1x10(-19) at 2000 s. This cascaded link was extended to 1480-km with the same performance. This work is a significant step towards a sustainable wide area ultra-stable optical frequency distribution and comparison network at a very high level of performance. PMID- 26832052 TI - Lasing properties of a cholesteric liquid crystal containing aggregation-induced emission material. AB - We demonstrate band edge lasing action from a cholesteric liquid crystal (CLC) containing an aggregation-induced-emission (AIE) dye as gain material. AIE materials do not suffer aggregation-caused quenching, have strong resistance to photobleaching, and can show large Stokes shift. The amplified spontaneous emission (ASE) and lasing emission of the dye-doped CLC cell have been characterized, the lasing threshold has been estimated, and its resistance to photobleaching has been measured. AIE materials with their unique properties are especially suitable for acting as gain materials in liquid crystal lasers where defect structures lower the threshold for nanoscale aggregation effects. Our studies have shown that such AIE-dye-doped CLC is capable of lasing action with unusually large Stokes shift at moderate threshold with strong resistance to photobleaching. PMID- 26832053 TI - Bright attosecond soft X-ray pulse trains by transient phase-matching in two color high-order harmonic generation. AB - We study two-color high-order harmonic generation in Neon with 790 nm and 1300 nm driving laser fields and observe an extreme-ultraviolet continuum that extends to photon energies of 160 eV. Using a 6-mm-long, high pressure gas cell, we optimize the HHG yield at high photon energies and investigate the effect of ionization and propagation under phase-matching conditions that allow us to control the temporal structure of the XUV emission. Numerical simulations that include the 3D propagation of the two-color laser pulse show that a bright isolated attosecond pulse with exceptionally high photon energies can be generated in our experimental conditions due to an efficient hybrid optical and phase-matching gating mechanism. PMID- 26832054 TI - Optical trapping performance of dielectric-metallic patchy particles. AB - We demonstrate a series of simulation experiments examining the optical trapping behavior of composite micro-particles consisting of a small metallic patch on a spherical dielectric bead. A full parameter space of patch shapes, based on current state of the art manufacturing techniques, and optical properties of the metallic film stack is examined. Stable trapping locations and optical trap stiffness of these particles are determined based on the particle design and potential particle design optimizations are discussed. A final test is performed examining the ability to incorporate these composite particles with standard optical trap metrology technologies. PMID- 26832055 TI - Creation of polarization gradients from superposition of counter propagating vector LG beams. AB - We present a detailed theoretical analysis of the formation of standing waves using cylindrically polarized vector Laguerre-Gaussian (LG) beams. It is shown that complex interplay between the radial and azimuthal polarization state can be used to realize different kinds of polarization gradients with cylindrically symmetric polarization distribution. Expressions for four different cases are presented and local dynamics of spatial polarization distribution is studied. We show cylindrically symmetric Sisyphus and corkscrew type polarization gradients can be obtained from vector LG beams. The optical landscape presented here with spatially periodic polarization patterns may find important applications in the field of atom optics, atom interferometry, atom lithography, and optical trapping. PMID- 26832056 TI - Controlling the effective second-order susceptibility in random quadratic media. AB - We study systematically the effect of spatial disorder of ferroelectric domains in nonlinear media on the polarization properties of optical frequency conversion. Experimentally, different statistics of domain sizes are created using electric field poling at room temperature. We analyze the evolution of polarization properties of the second- and third-harmonic signals for each created statistic by determining the corresponding relative strength of non-zero components of the second-order susceptibility tensor, d24, d32 and d33. The relative strengths are labeled by means of the control parameter E on the characteristic P-E loop of the studied ferroelectric medium. PMID- 26832057 TI - Automatic airway wall segmentation and thickness measurement for long-range optical coherence tomography images. AB - We present an automatic segmentation method for the delineation and quantitative thickness measurement of multiple layers in endoscopic airway optical coherence tomography (OCT) images. The boundaries of the mucosa and the sub-mucosa layers are accurately extracted using a graph-theory-based dynamic programming algorithm. The algorithm was tested with sheep airway OCT images. Quantitative thicknesses of the mucosal layers are obtained automatically for smoke inhalation injury experiments. PMID- 26832058 TI - Accelerating decomposition of light field video for compressive multi-layer display. AB - Compressive light field display based on multi-layer LCDs is becoming a popular solution for 3D display. Decomposing light field into layer images is the most challenging task. Iterative algorithm is an effective solver for this high dimensional decomposition problem. Existing algorithms, however, iterate from random initial values. As such, significant computation time is required due to the deviation between random initial estimate and target values. Real-time 3D display at video rate is difficult based on existing algorithms. In this paper, we present a new algorithm to provide better initial values and accelerate decomposition of light field video. We utilize internal coherence of single light field frame to transfer the ignorance-to-target to a much lower resolution level. In addition, we explored external coherence for further accelerating light field video and achieved 5.91 times speed improvement. We built a prototype and developed parallel algorithm based on CUDA. PMID- 26832059 TI - Infrared hyperspectral upconversion imaging using spatial object translation. AB - In this paper hyperspectral imaging in the mid-infrared wavelength region is realised using nonlinear frequency upconversion. The infrared light is converted to the near-infrared region for detection with a Si-based CCD camera. The object is translated in a predefined grid by motorized actuators and an image is recorded for each position. A sequence of such images is post-processed into a series of monochromatic images in a wavelength range defined by the phasematch condition and numerical aperture of the upconversion system. A standard USAF resolution target and a polystyrene film are used to impart spatial and spectral information unto the source. PMID- 26832060 TI - Transverse spin angular momentum of tightly focused full Poincare beams. AB - We show theoretically that by tightly focusing a full Poincare beam one can create states of light whose average spin angular momentum (SAM) is purely transverse. Moreover, the transverse SAM is significantly increased if a narrow annular aperture is inserted into the Poincare beam. In this case the state with transverse SAM can exist over an extremely long distance along the optical axis. To avoid diffraction on the aperture and increase the light conversion efficiency we employ the phenomenon of conical diffraction in biaxial crystals to convert a Gaussian beam into a ring-shaped beam, with a high ratio of the ring radius to its width. PMID- 26832061 TI - Multi-fields direct design approach in 3D: calculating a two-surface freeform lens with an entrance pupil for line imaging systems. AB - Including an entrance pupil in optical systems provides clear benefits for balancing the overall performance of freeform and/or rotationally symmetric imaging systems. Current existing direct design methods that are based on perfect imaging of few discrete ray bundles are not well suited for wide field of view systems. In this paper, a three-dimensional multi-fields direct design approach is proposed to balance the full field imaging performance of a two-surface freeform lens. The optical path lengths and image points of numerous fields are calculated during the procedures, wherefore very few initial parameters are needed in advance. Design examples of a barcode scanner lens as well as a line imaging objective are introduced to demonstrate the effectiveness of this method. PMID- 26832062 TI - Transient flickering behavior in fringe-field switching liquid crystal mode analyzed by positional asymmetric flexoelectric dynamics. AB - We analyzed a transient blinking phenomenon in a fringe-field switching liquid crystal (LC) mode that occurred at the moment of frame change even in the optimized DC offset condition for minimum image flicker. Based on the positional dynamic behaviors of LCs by using a high-speed camera, we found that the transient blink is highly related to the asymmetric responses of the splay-bend transitions caused by the flexoelectric (FE) effect. To remove the transient blink, the elastic property adjustment of LCs was an effective solution because the FE switching dynamics between the splay-enhanced and bend-enhanced deformations are highly dependent on the elastic constants of LCs, which is the cause of momentary brightness drop. PMID- 26832063 TI - Electro-optical switching of liquid crystals sandwiched between ion-beam-spurted graphene quantum dots-doped PEDOT:PSS composite layers. AB - Graphene quantum dots (GQDs)-doped PEDOT: PSS composite layers were utilized to align liquid crystals (LCs) via an ion-beam (IB)-spurting pre-treatment process. LCs were homogeneously aligned between sandwiched GQDs/ PEDOT: PSS composite thin layers, and the alignment of LCs was found to be affected by both the quantity of doped GQDs and IB-spurting intensity. Competitive electro-optical switching properties and non-residual DC performance of the cell equipped with GQDs/ PEDOT: PSS composite alignment layers were obtained because of the enhanced field effect and charge transport induced by doped GQDs. Notably, using IB-spurted GQDs/ PEDOT: PSS layers as alignment layers for next generation high-performance liquid crystal display (LCD) is promising. PMID- 26832064 TI - Single-shot temporal envelope measurement of ultrashort extreme-UV pulses by spatially encoded transmission gating. AB - Single-shot ultrashort extreme-UV(EUV) pulse waveform measurement is demonstrated by utilizing strong field ionization of H2 gas for transmission gating. A cross propagating intense near-IR gate pulse ionizes the EUV absorbing H2 molecules into EUV-non-absorbing H2++ (two protons) and creates a time sweep of transmission encoded spatially across the EUV pulse. The temporal envelope is then retrieved from the lopsided spatial profile of the transmitted pulse. This method not only measures EUV temporal envelope for each single shot, but also determines timing jitter and envelope fluctuation statistically, thus is particularly useful for characterizing low-repetition-rate fluctuating EUV/soft x ray sources. PMID- 26832065 TI - Cycle of phase, coherence and polarization singularities in Young's three-pinhole experiment. AB - It is now well-established that a variety of singularities can be characterized and observed in optical wavefields. It is also known that these phase singularities, polarization singularities and coherence singularities are physically related, but the exact nature of their relationship is still somewhat unclear. We show how a Young-type three-pinhole interference experiment can be used to create a continuous cycle of transformations between classes of singularities, often accompanied by topological reactions in which different singularities are created and annihilated. This arrangement serves to clarify the relationships between the different singularity types, and provides a simple tool for further exploration. PMID- 26832066 TI - Topological charge algebra of optical vortices in nonlinear interactions. AB - We investigate the transfer of orbital angular momentum among multiple beams involved in a coherent Raman interaction. We use a liquid crystal light modulator to shape pump and Stokes beams into optical vortices with various integer values of topological charge, and cross them in a Raman-active crystal to produce multiple Stokes and anti-Stokes sidebands. We measure the resultant vortex charges using a tilted-lens technique. We verify that in every case the generated beams' topological charges obey a simple relationship, resulting from angular momentum conservation for created and annihilated photons, or equivalently, from phase-matching considerations for multiple interacting beams. PMID- 26832067 TI - The Current State of Pediatric Sports Medicine: A Workforce Analysis. AB - OBJECTIVE: Pediatric sports medicine is an evolving pediatric subspecialty. No workforce data currently exists describing the current state of pediatric sports medicine. The goal of this survey is to contribute information to the practicing pediatric sports medicine specialist, employers and other stakeholders regarding the current state of pediatric sports medicine. METHODS: The Workforce Survey was conducted by the American Academy of Pediatrics (AAP) Division of Workforce and Medical Education Policy (WMEP) and included a 44-item standard questionnaire online addressing training, clinical practice and demographic characteristics as well as the 24-item AAP Council on Sports Medicine and Fitness (COSMF) questionnaire. Descriptive statistics were used to summarize all survey responses. Bivariate relationships were tested for statistical significance using Chi square. RESULTS: 145 surveys were returned, which represented a 52.7% response rate for eligible COSMF members and board certified non-council responders. The most common site of employment among respondents was university based clinics. The respondents board certified in sports medicine were significantly more likely to perform fracture management, casting and splinting, neuropsychological testing and injections compared to those not board certified in sports medicine. A large proportion of respondents held an academic/medical school appointment. Increases were noted in both patient volume and the complexity of the injuries the specialists were treating. CONCLUSION: This pediatric sports medicine workforce study provides previously unappreciated insight into practice arrangements, weekly duties, procedures, number of patients seen, referral patterns, and potential future trends of the pediatric sports medicine specialist. PMID- 26832068 TI - The influence of zero-flux surface motion on chemical reactivity. AB - Visualizing and predicting the response of the electron density, rho(r), to an external perturbation provides a portion of the insight necessary to understand chemical reactivity. One strategy used to portray electron response is the electron pushing formalism commonly utilized in organic chemistry, where electrons are pictured as flowing between atoms and bonds. Electron pushing is a powerful tool, but does not give a complete picture of electron response. We propose using the motion of zero-flux surfaces (ZFSs) in the gradient of the charge density, ?rho(r), as an adjunct to electron pushing. Here we derive an equation rooted in conceptual density functional theory showing that the movement of ZFSs contributes to energetic changes in a molecule undergoing a chemical reaction. Using a substituted acetylene, 1-iodo-2-fluoroethyne, as an example, we show the importance of both the boundary motion and the change in electron counts within the atomic basins of the quantum theory of atoms in molecules for chemical reactivity. This method can be extended to study the ZFS motion between smaller gradient bundles in rho(r) in addition to larger atomic basins. Finally, we show that the behavior of ?rho(r) within atomic basins contains information about electron response and can be used to predict chemical reactivity. PMID- 26832069 TI - Proteolytic and non-proteolytic regulation of collective cell invasion: tuning by ECM density and organization. AB - Cancer cells manoeuvre through extracellular matrices (ECMs) using different invasion modes, including single cell and collective cell invasion. These modes rely on MMP-driven ECM proteolysis to make space for cells to move. How cancer associated alterations in ECM influence the mode of invasion remains unclear. Further, the sensitivity of the two invasion modes to MMP dynamics remains unexplored. In this paper, we address these open questions using a multiscale hybrid computational model combining ECM density-dependent MMP secretion, MMP diffusion, ECM degradation by MMP and active cell motility. Our results demonstrate that in randomly aligned matrices, collective cell invasion is more efficient than single cell invasion. Although increase in MMP secretion rate enhances invasiveness independent of cell-cell adhesion, sustenance of collective invasion in dense matrices requires high MMP secretion rates. However, matrix alignment can sustain both single cell and collective cell invasion even without ECM proteolysis. Similar to our in-silico observations, increase in ECM density and MMP inhibition reduced migration of MCF-7 cells embedded in sandwich gels. Together, our results indicate that apart from cell intrinsic factors (i.e., high cell-cell adhesion and MMP secretion rates), ECM density and organization represent two important extrinsic parameters that govern collective cell invasion and invasion plasticity. PMID- 26832070 TI - Grafting cucumber onto luffa improves drought tolerance by increasing ABA biosynthesis and sensitivity. AB - Balancing stomata-dependent CO2 assimilation and transpiration is a key challenge for increasing crop productivity and water use efficiency under drought stress for sustainable crop production worldwide. Here, we show that cucumber and luffa plants with luffa as rootstock have intrinsically increased water use efficiency, decreased transpiration rate and less affected CO2 assimilation capacity following drought stress over those with cucumber as rootstock. Drought accelerated abscisic acid (ABA) accumulation in roots, xylem sap and leaves, and induced the transcript of ABA signaling genes, leading to a decreased stomatal aperture and transpiration in the plants grafted onto luffa roots as compared to plants grafted onto cucumber roots. Furthermore, stomatal movement in the plants grafted onto luffa roots had an increased sensitivity to ABA. Inhibition of ABA biosynthesis in luffa roots decreased the drought tolerance in cucumber and luffa plants. Our study demonstrates that the roots of luffa have developed an enhanced ability to sense the changes in root-zone moisture and could eventually deliver modest level of ABA from roots to shoots that enhances water use efficiency under drought stress. Such a mechanism could be greatly exploited to benefit the agricultural production especially in arid and semi-arid areas. PMID- 26832071 TI - Laboratory rearing of wild Arctic cod Boreogadus saida from egg to adulthood. AB - The techniques and protocols used to successfully capture, transport and breed Arctic cod Boreogadus saida, as well as to rear their larvae through to adulthood are summarized. Breeding B. saida will increase the opportunity to study this fish species, which is a critical part of the Arctic food web. PMID- 26832072 TI - Necessary Infrastructure of Infection Prevention and Healthcare Epidemiology Programs: A Review. AB - The scope of a healthcare institution's infection prevention and control/healthcare epidemiology program (IPC/HE) should be driven by the size and complexity of the patient population served, that population's risk for healthcare-associated infection (HAI), and local, state, and national regulatory and accreditation requirements. Essential activities of all IPC/HE programs include but are not limited to the following: ? Surveillance.? Performance improvement to reduce HAI ? Acute event response, including outbreak investigation ? Education and training of both healthcare personnel and patients ? Reporting of HAI to the Centers for Disease Control and Prevention's National Healthcare Safety Network as well as entities required by law. PMID- 26832073 TI - Dead fungal mycelium in forest soil represents a decomposition hotspot and a habitat for a specific microbial community. AB - Turnover of fungal biomass in forest litter and soil represents an important process in the environment. To date, knowledge of mycelial decomposition has been derived primarily from short-term studies, and the guild of mycelium decomposers has been poorly defined. Here, we followed the fate of the fruiting bodies of an ectomycorrhizal fungus in litter and soil of a temperate forest over 21 wk. The community of associated microbes and enzymatic processes in this specific substrate were described. The decomposition of fungal fruiting bodies exhibited biphasic kinetics. The rapid initial phase, which included the disappearance of DNA, was followed by a slower turnover of the recalcitrant fraction. Compared with the surrounding litter and soil, the mycelium represented a hotspot of activity of several biopolymer-degrading enzymes and high bacterial biomass. Specific communities of bacteria and fungi were associated with decomposing mycelium. These communities differed between the initial and late phases of decomposition. The bacterial community associated with decomposing mycelia typically contained the genera Pedobacter, Pseudomonas, Variovorax, Chitinophaga, Ewingella and Stenotrophomonas, whereas the fungi were mostly nonbasidiomycetous r-strategists of the genera Aspergillus, Penicillium, Mortierella, Cladosporium and several others. Decomposing ectomycorrhizal fungal mycelium exhibits high rates of decomposition and represents a specific habitat supporting a specific microbial community. PMID- 26832074 TI - Electrolytic and electro-irradiated processes with diamond anodes for the oxidation of persistent pollutants and disinfection of urban treated wastewater. AB - This paper analyzes the advantages and drawbacks of the combination of UV irradiation with electrolysis with the aim to give insight about the feasibility of the application of this technology for the reclaiming of conventionally treated wastewater. The oxidation of synthetic solutions containing five selected model complex pollutants has been compared, showing that UV irradiation improves the results of electrolysis for progesterone, metoprolol and caffeine and deteriorates the performance for the degradation of sulfamethoxazole and dimethyl phthalate. Differences observed becomes lower when mineralization is compared showing that the effects of UV irradiation are diluted when a mixture of species is oxidized. Results suggest that high ThOD/TOC (Theoretical Oxygen Demand/Total Organic Carbon) ratios improve the synergistic coupling of technologies while low values lead to a clear antagonistic effect. Because during oxidation progress this ratio is decreased, the observed effect on mineralization is much lower than in the oxidation of the raw molecule. Opposite to this low effect on the oxidation of organics, the improvement in the performance of the disinfection by coupling UV to electrolysis is much clearer. In addition, UV irradiation modifies significantly the chlorine speciation and helps to prevent the formation of hazardous species such as chlorate and perchlorate during the electrochemical processes. PMID- 26832075 TI - Leaching and selective zinc recovery from acidic leachates of zinc metallurgical leach residues. AB - Zinc (Zn) leaching yields and kinetics from three different zinc plant leach residues (ZLR) generated in different periods (ZLR1>30 years, ZLR2 5-30 years and ZLR3<2 years) were investigated. The factors affecting the Zn leaching rate such as solid to liquid ratio, temperature, acid concentration and agitation were optimized. Under optimum conditions, 46.2 (+/-4.3), 23.3 (+/-2.7) and 17.6 (+/ 1.2) mg of Zn can be extracted per gram of ZLR1, ZLR2 and ZLR3, respectively. The Zn leaching kinetics of ZLRs follow the shrinking core diffusion model. The activation energy required to leach Zn from ZLR1, ZLR2 and ZLR3 were estimated to be 2.24kcal/mol, 6.63kcal/mol and 11.7kcal/mol, respectively, by the Arrhenius equation. The order of the reaction with respect to the sulfuric acid concentration was also determined as 0.20, 0.56, and 0.87 for ZLR1, ZLR2 and ZLR3, respectively. Zn was selectively recovered from the leachates by adjusting the initial pH and by the addition of sodium hydroxide and sodium sulfide. More than 90% of Zn was selectively recovered as sphalerite from the ZLR polymetallic leachates by chemical sulfide precipitation. PMID- 26832076 TI - Effectiveness of platysma muscle flap in preventing Frey syndrome and depressive deformities after parotidectomy. AB - BACKGROUND: Frey syndrome (FS) or depressive deformity (DD) occurring after parotidectomy significantly reduces a patient's quality of life. However, there seems to be no effective treatment strategy against these complications. In this study, we report our experience of using platysma muscle flap (PMF) to prevent the development of FS and DD after parotidectomy, and evaluate its effect subjectively and objectively. METHODS: Superficial parotidectomy was performed for eight cases of parotid gland tumor, and a PMF was transferred to cover the site. The incidence of FS and DD were evaluated subjectively, using a questionnaire to the patients and board-certified reconstructive surgeons, and objectively, using Minor's starch-iodine test. RESULTS: In seven patients, the defect could be completely covered with PMF, and none of them developed FS or obvious DD. However, in one patient, the defect could be only partially covered, and the patient developed complications in the exact site that the flap did not cover. Overall scores from the questionnaire were high in relation to both cosmetic and functional perspectives from most of the patients and all the surgeons. No patients had major postoperative complications requiring revision. CONCLUSIONS: PMF can be useful to cover the defect and prevent complications after parotidectomy. PMF is relatively easy to perform with fewer complications; however, a complete coverage of the defect should be ensured to obtain optimal results. PMID- 26832077 TI - Can standard endovascular abdominal aortic aneurysm repair be performed as a day case in selected patients? PMID- 26832078 TI - Restricting Choices of Childbearing Women. PMID- 26832079 TI - Fetal Risks, Relative Risks, and Relatives' Risks. AB - Several factors related to fetal risk render it more or less acceptable in justifying constraints on the behavior of pregnant women. Risk is an unavoidable part of pregnancy and childbirth, one that women must balance against other vital personal and family interests. Two particular issues relate to the fairness of claims that pregnant women are never entitled to put their fetuses at risk: relative risks and relatives' risks. The former have been used-often spuriously to advance arguments against activities, such as home birth, that may incur risk; the latter implicate the nature of relationships in determining the acceptability of coercing or precluding activities. Motivated reasoning by clinicians and judges leads to inaccurate risk assessments, and judgments based on false claims to objectivity. Such judgments undermine the moral and legal standing of pregnant women and do not advance the interests of fetuses, pregnant women, families, or states. PMID- 26832080 TI - Fetal Risk, Fetal Purity, and the Perils Posed by Pregnant Women. PMID- 26832081 TI - Protecting Intended Children From Harmful Prenatal Conduct. PMID- 26832082 TI - It Matters That Prenatal Humans Are Not Constitutional Persons. PMID- 26832083 TI - For Whom the Burden Tolls: Gender and the Unequal Management of Fetal Risks and Parental Expectations. PMID- 26832084 TI - Regulating Risk and the Boundaries of State Conduct: A Relational Perspective on Home Birth in Australia. PMID- 26832085 TI - Pregnancy and the Culture of Extreme Risk Aversion. PMID- 26832086 TI - The Invisible Pregnant Woman. PMID- 26832087 TI - Relative Risk and Relatives' Risks in Genomic Medicine. PMID- 26832088 TI - Parental Obligations Regarding Fetal Risk: Finding the Appropriate Analogy. PMID- 26832089 TI - Fetal Risks and Religious Obligations. PMID- 26832090 TI - Reducing Unreasonable Bias and Risk in Decisions Regarding the Care of Pregnant Women. PMID- 26832091 TI - Ambiguous Interests: Maternal Desires and Fetal Interests. PMID- 26832092 TI - The Porosity of Autonomy: Social and Biological Constitution of the Patient in Biomedicine. AB - The nature and role of the patient in biomedicine comprise issues central to bioethical inquiry. Given its developmental history grounded firmly in a backlash against 20th-century cases of egregious human subjects abuse, contemporary medical bioethics has come to rely on a fundamental assumption: the unit of care (and the unit of value) is the autonomous self-directing patient. In this article we examine first the structure of the feminist social critique of autonomy. Then we show that a parallel argument can be made against relational autonomy as well, demonstrating how this second concept of autonomy fails to take sufficiently into account an array of biological determinants, particularly those from microbial biology. Finally, in light of this biological critique, we question whether or to what extent any relevant and meaningful view of autonomy can be recovered in the contemporary landscape of bioethics. PMID- 26832093 TI - The Irrelevance of Ontology for the Ethics of Autonomy. PMID- 26832094 TI - Porous or Contextualized Autonomy? Knowledge Can Empower Autonomous Moral Agents. PMID- 26832095 TI - Reinterpreting Respect for Relationally and Biologically Informed Autonomy. PMID- 26832096 TI - Expanding the Biological Critique to Address the Influence of the Endocrine System. PMID- 26832097 TI - Microbes and Medical Decisions. PMID- 26832098 TI - Don't Throw Out the Baby of Autonomy: Talk to the Mother Instead. PMID- 26832099 TI - The Myth of the Individual. PMID- 26832100 TI - How To Think About the Individual as a Nonautonomous Community. PMID- 26832101 TI - The Complexity of Relational Autonomy: A Holistic Approach to Embodiment. PMID- 26832102 TI - Idealist-Atomist Autonomy and the Commercialization of Biomedicine. PMID- 26832103 TI - Parental Neglect or Appropriate End-of-Life Care? PMID- 26832104 TI - Commentary From a Pediatric Complexologist and a Pediatric Palliative Care and Ethics Consultant. PMID- 26832105 TI - Thoughtfulness and Grace: End-of-Life Decision Making for Children With Severe Developmental Disabilities. PMID- 26832106 TI - When Physicians and a Parent Conflict on When to Limit Treatment for a Child With Significant Disabilities. PMID- 26832107 TI - Alone and Saying No. PMID- 26832108 TI - Another Kind of Diversity: Honoring-or Not-the Decisions of People Who Refuse Care. PMID- 26832109 TI - The CASES Approach to Ethics Consultation: The Centrality of the Ethics Question. PMID- 26832110 TI - Incapacitated and Surrogateless Patients: Decision Making for the Surrogateless Patient: An Attempt to Improve Decision Making. PMID- 26832112 TI - A Response to the Open Peer Commentaries on "Young People's Experiences of Participation in Clinical Trials: Reasons for Taking Part". PMID- 26832113 TI - Response to Open Peer Commentaries on "Fetal Risks, Relative Risks, and Relatives' Risks". PMID- 26832115 TI - The Role of Patient Perspectives in Clinical Research Ethics and Policy: Response to Open Peer Commentaries on "Patient Perspectives on the Learning Health System". PMID- 26832116 TI - [Hip fractures in an elderly cohort with decreased glomerular filtration rate (non-dialysis)]. PMID- 26832117 TI - The plasma membrane protein Rch1 is a negative regulator of cytosolic calcium homeostasis and positively regulated by the calcium/calcineurin signaling pathway in budding yeast. AB - Saccharomyces cerevisiae Rch1 is structurally similar to both the vertebrate solute carrier SLC10A7 and Candida albicans Rch1. We show here that ScRCH1 is a functional homolog of CaRCH1. In S. cerevisiae, overexpression of ScRCH1 suppresses, but deletion of ScRCH1 does not affect, the lithium and rapamycin tolerance of pmr1 cells. Overexpression of ScRCH1 reduces expression of ENA1, prevents sustained accumulation of cytosolic calcium and reduces the activation level of calcium/calcineurin signaling in pmr1 cells. Therefore, similar to the situation in the pathogen C. albicans, ScRch1 negatively regulates the cytosolic homeostasis in response to high levels of extracellular calcium. ScRch1 proteins distribute as multiple foci in the plasma membrane prior to cell division, move toward and concentrate at the bud neck as the bud grows in size, and disperse again along the plasma membrane immediately prior to cytokinesis. Furthermore, our genetic and biochemical data also demonstrate that transcriptional expression of RCH1 is positively regulated by calcium/calcineurin signaling through the sole CDRE element in its promoter. PMID- 26832119 TI - Breakfast: how important is it really? PMID- 26832118 TI - Nucleotide Catabolism on the Surface of Aortic Valve Xenografts; Effects of Different Decellularization Strategies. AB - Extracellular nucleotide metabolism controls thrombosis and inflammation and may affect degeneration and calcification of aortic valve prostheses. We evaluated the effect of different decellularization strategies on enzyme activities involved in extracellular nucleotide metabolism. Porcine valves were tested intact or decellularized either by detergent treatment or hypotonic lysis and nuclease digestion. The rates of ATP hydrolysis, AMP hydrolysis, and adenosine deamination were estimated by incubation of aorta or valve leaflet sections with substrates followed by HPLC analysis. We demonstrated relatively high activities of ecto-enzymes on porcine valve as compared to the aortic wall. Hypotonic lysis/nuclease digestion preserved >80 % of ATP and AMP hydrolytic activity but reduced adenosine deamination to <10 %. Detergent decellularization completely removed (<5 %) all these activities. These results demonstrate high intensity of extracellular nucleotide metabolism on valve surface and indicate that various valve decellularization techniques differently affect ecto-enzyme activities that could be important in the development of improved valve prostheses. PMID- 26832120 TI - [Proliferative verrucous leukoplakia: Three cases and literature review]. AB - BACKGROUND: The aim of this study was to collect epidemiological, aetiopathogenic, clinical, histological and therapeutic data concerning proliferative verrucous leucoplakia (PVL) and to report three new cases. PATIENTS AND METHODS: A literature review performed using the Medline database enabled us to collate 39 studies involving 607 cases. Three new cases were added. RESULTS: PVL is a rare disease characterized by extensive and multifocal oral leucoplakic lesions. Its histological pattern depends on the stage of the disease: hyperkeratosis, verrucous hyperplasia, verrucous carcinoma and squamous cell carcinoma. The aetiopathogenesis of PVL is poorly understood and there is no clear consensus concerning therapy. Malignant transformation occurs in over 50 % of cases. DISCUSSION: Diagnosis of PVL is difficult because of the presenting signs, which can be mistaken for those of other diseases. Management may be complicated and long-term follow-up is essential. PMID- 26832122 TI - Exploring the Relationships Between Problem Gambling and ADHD: A Meta-Analysis. AB - OBJECTIVE: At present, there are inconsistencies in the literature pertaining to the association between ADHD and problem gambling. This study utilized meta analytic techniques to clarify the association between symptoms of problem gambling and symptoms of ADHD. METHOD: Several meta-analyses were conducted using a random effects model. PsycINFO, PubMed, ProQuest Dissertations & Theses, and Google Scholar were searched for relevant studies. RESULTS: The weighted mean correlation between ADHD symptomology and gambling severity was r = .17, 95% confidence interval (CI) = [0.12, 0.22], p < .001. Mean age of the sample was the only moderator to approach significance, with greater age being linked to a stronger relationship between symptoms of ADHD and gambling severity. CONCLUSION: Clinicians needs to be cognizant of the greater risk of ADHD symptoms when working with problem gamblers and vice versa. PMID- 26832121 TI - Growth temperature impact on leaf form and function in Arabidopsis thaliana ecotypes from northern and southern Europe. AB - The plasticity of leaf form and function in European lines of Arabidopsis thaliana was evaluated in ecotypes from Sweden and Italy grown under contrasting (cool versus hot) temperature regimes. Although both ecotypes exhibited acclimatory adjustments, the Swedish ecotype exhibited more pronounced responses to the two contrasting temperature regimes in several characterized features. These responses included thicker leaves with higher capacities for photosynthesis, likely facilitated by a greater number of phloem cells per minor vein for the active loading and export of sugars, when grown under cool temperature as opposed to leaves with a higher vein density and a greater number of tracheary elements per minor vein, likely facilitating higher rates of transpirational water loss (and thus evaporative cooling), when grown under hot temperature with high water availability. In addition, only the Swedish ecotype exhibited reduced rosette growth and greater levels of foliar tocopherols under the hot growth temperature. These responses, and the greater responsiveness of the Swedish ecotype compared with the Italian ecotype, are discussed in the context of redox signalling networks and transcription factors, and the greater range of environmental conditions experienced by the Swedish versus the Italian ecotype during the growing season in their native habitats. PMID- 26832123 TI - Unilateral Erythematous Lesions with Wax-like Scaling and Limb Abnormalities: A Quiz. PMID- 26832124 TI - In vivo longitudinal study of rodent skeletal muscle atrophy using ultrasonography. AB - Muscle atrophy is a widespread ill condition occurring in many diseases, which can reduce quality of life and increase morbidity and mortality. We developed a new method using non-invasive ultrasonography to measure soleus and gastrocnemius lateralis muscle atrophy in the hindlimb-unloaded rat, a well-accepted model of muscle disuse. Soleus and gastrocnemius volumes were calculated using the conventional truncated-cone method and a newly-designed sinusoidal method. For Soleus muscle, the ultrasonographic volume determined in vivo with either method was linearly correlated to the volume determined ex-vivo from excised muscles as muscle weight-to-density ratio. For both soleus and gastrocnemius muscles, a strong linear correlation was obtained between the ultrasonographic volume and the muscle fiber cross-sectional area determined ex-vivo on muscle cryosections. Thus ultrasonography allowed the longitudinal in vivo evaluation of muscle atrophy progression during hindlimb unloading. This study validates ultrasonography as a powerful method for the evaluation of rodent muscle atrophy in vivo, which would prove useful in disease models and therapeutic trials. PMID- 26832125 TI - One year of training with FES has impressive beneficial effects in a 36-year-old woman with spinal cord injury. AB - CONTEXT: Reductions of muscular and cardiorespiratory functions are often observed in people with spinal cord injury (SCI) and several studies demonstrated the benefits of aerobic and strengthening exercise training for this population. Functional Electrical Stimulation (FES) of paralyzed muscles has been proposed as a strategy to assist patients in executing functional movement but its utilization during long durations has never been investigated. The purpose of the present study was to assess the effects of a one-year training program with FES (strengthening and rowing) in one subject with SCI. Evoked torque, quadriceps muscle thickness, aerobic exercise capacity and bone mineral density were tested. FINDINGS: All parameters increased after training: average evoked torque +151%, quadriceps muscle thickness +136%, thigh circumference +14%, bone density +19%, maximal oxygen uptake +76% and oxygen uptake at ventilatory threshold +111%. CONCLUSION: These impressive improvements demonstrate that FES training offers several interesting clinical benefits in a patient with SCI. PMID- 26832126 TI - Modifying Effect of Body Mass Index on Survival in Elderly Type 2 Diabetic Patients: Hong Kong Diabetes Registry. AB - OBJECTIVE: There are nonlinear risk associations of body mass index (BMI) with mortality in type 2 diabetes (T2D) and elderly populations although similar information in elderly individuals with T2D are lacking. RESEARCH DESIGN AND METHODS: We analyzed prospective data for 3186 Chinese patients with T2D with age 65 years or older. Baseline demographic data, risk factors, complications, and all-cause mortality were captured from the Hong Kong Diabetes Registry and the Hong Kong Hospital Authority Clinical Management System. RESULTS: Over a median follow-up period of 6.0 years (medium-term), 816 (25.6%) deaths occurred and at 9.4 years (long-term), 1557 (48.9%) patients had died. Men were more likely to die than women with increased mortality rate with increasing age (morality rates of men with normal BMI at 9-year follow-up in the 65 to 69, 70 to 74, and 75 years or older age groups were 41.8, 70.3, and 101.4 per 1000 person-years, whereas that for women were 35.5, 50.4, and 78.8 respectively). Within each age group, high BMI was associated with increased survival, especially in the 75 years and older age group and with prolonged follow-up period. Using Cox regression analysis, after adjustment for confounders, high BMI (>= 25.0 kg/m(2)) was associated with reduced risk of death in all subgroups, reaching significance in men in the older age groups at 9-year follow-up (for men 70 to 74 years old, hazard ratio [HR] of mortality was 0.67, 95% confidence interval [CI] 0.48-0.95, for those >= 75, HR was 0.62, 95% CI 0.44-0.89) compared with 18.5 to 22.9 kg/m(2) as referent. CONCLUSIONS: In Chinese elderly patients with T2D, high BMI protected against mortality, calling for more attention to people with low BMI who might have unmet clinical needs. PMID- 26832127 TI - The Effect of Age in the Association between Frailty and Poor Sleep Quality: A Population-Based Study in Community-Dwellers (The Atahualpa Project). AB - PURPOSE: To assess the effect of age in the association between poor sleep quality and frailty status. DESIGN AND SETTING: Population-based, cross-sectional study conducted in Atahualpa, a rural village located in coastal Ecuador. METHODS: Out of 351 Atahualpa residents aged >= 60 years, 311 (89%) were interviewed with the Pittsburgh Sleep Quality Index (PSQI) and the Edmonton Frail Scale (EFS). The independent association between PSQI and EFS scores was evaluated by the use of a generalized linear model adjusted for relevant confounders. A contour plot with Shepard interpolation was constructed to assess the effect of age in this association. RESULTS: Mean score in the PSQI was 5 +/- 2 points, with 34% individuals classified as poor sleepers. Mean score in the EFS was 5 +/- 3 points, with 46% individuals classified as robust, 23% as prefrail, and 31% as frail. In the fully adjusted model, higher scores in the PSQI were significantly associated with higher scores in the EFS (beta 0.23; 95% CI 0.11 0.35; P < .0001). Several clusters depicted the strong effect of age in the association between PSQI and EFS scores. Older individuals were more likely to have high scores in the EFS and the PSQI, and younger individuals had low EFS scores and were good sleepers. Clusters of younger individuals who were poor sleepers and had high EFS scores accounted for the independent association between PSQI and EFS scores. CONCLUSIONS: This study shows the strong effect of age in the association between poor sleep quality and frailty status. PMID- 26832128 TI - Outcomes of Young Patients With Rectal Cancer From a Tertiary Cancer Care Centre in India. AB - BACKGROUND: Carcinoma of the rectum is the fourth most common cancer in the world. The peak age of diagnosis is around the seventh decade. Rectal cancer presenting in those < 35 years old are very peculiar in that they present with adverse histologic features and more advanced stage compared with rectal cancer presenting in older patients. MATERIALS AND METHODS: We retrospectively evaluated the patient records of young patients with rectal cancer (aged < 35 years) treated in our unit at the All India Institute from 2007 to 2013. RESULTS: A total of 60 young patients with rectal cancer were registered in our unit during the study period. A family history of cancer was present in 3 patients. The median age at presentation was 27.5 years (range, 15-34 years). The male-to female ratio was 1.5:1. Of the 60 patients, 52 (86.6%) presented with advanced stage disease (stage III and IV). Mucinous, signet, papillary, and other poor risk histologic features were seen in 33 patients (55%). The treatment intention was radical for 50 patients (83.3%). The median follow-up period was 7.3 months. Eighteen patients had documented disease progression. Distant metastasis was the most common type of failure, seen in 14 of 18 patients (77%). The median progression-free survival (PFS) was 1.4 years. The 1- and 3-year PFS rates were 66.5% and 42.0%, respectively. On univariate analysis, the Karnofsky performance status and histologic type were significant prognostic factors for PFS. CONCLUSION: A greater proportion of poor histologic subtypes was found among young patients with rectal cancer. The high incidence of poor histologic subtypes confers a poor prognosis in these patients. PMID- 26832129 TI - [Nutrition in overweight and obesity with a specific focus on gender aspects]. AB - Efforts to optimize the diet in terms of prevention and treatment of obesity aim at long-term adaptation and reduction of energy intake according to age and physiological requirements while preserving the nutrient density with consideration of individual food preferences.As the nutritional habits of the average Austrian people are unfavorable for obesity prevention there is a clear need for action. Women are "disadvantaged" in weight control compared to men in terms of physiological conditions-and are confronted with specific needs during life course (e.g. pregnancy), whereas the average man or male adolescents present "unhealthier" behaviors and attitudes and are (still) less interested on nutrition or weight control.To achieve better nutrition a target-group specific, gender-sensitive guidance of the individual is needed, starting with pregnant women, but also habitat-oriented interventions for improved nutrition offers, which have to be sustainably assured through the support of a relevant legal and social framework. PMID- 26832130 TI - Factors impacting sodium restriction in patients with chronic kidney disease: a cohort study from a Chinese center. AB - PURPOSE: Sodium restriction is important for the management of chronic kidney disease (CKD). The present study evaluated the factors impacting dietary sodium restriction in a cohort of Chinese patients with CKD. METHODS: A questionnaire on dietary sodium restriction was administered to patients with non-dialysis CKD who visited our CKD clinic from September 2014 to March 2015. Twenty-four-hour urinary sodium excretion (24-h UNa) was measured. Logistic regression was performed to examine the association between patient characteristics and sodium restriction. RESULTS: Two hundred and twenty-nine patients were included in the final analysis. Most of the patients (97.7 %) declared their awareness of the necessity of sodium restriction, but 27.3 % of them chose an incorrect sodium restriction limit. Most of the patients (85.2 %) also reported that they had taken actions to reduce their sodium consumption, with intolerance of sodium restriction as the most common reason for taking no actions. Only 42 patients (18.3 %) had a 24-h UNa of <100 mmol. Multivariable logistic regression showed that age and the use of condiments were independently associated with successful sodium restriction [odds ratio (95 % confidence interval) 1.04 (1.01-1.07), p = 0.006 and 0.38 (0.16-0.88), p = 0.023, respectively]. Most of the patients (83.0 %) did not know how to estimate their sodium intake from condiments. CONCLUSIONS: This study indicates that there is much room for improvement in dietary sodium restriction in Chinese patients with CKD. Condiments as a hidden source of sodium intake should be stressed in the education of these patients. PMID- 26832132 TI - Bacillus nitroreducens sp. nov., a humus-reducing bacterium isolated from a compost. AB - A Gram-staining-positive, facultative anaerobic, motile and rod-shaped bacterium, designated GSS08(T), was isolated from a windrow compost pile and characterized by means of a polyphasic approach. Growth occurred with 0-4 % (w/v) NaCl (optimum 1 %), at pH 6.5-9.5 (optimum pH 7.5) and at 20-45 degrees C (optimum 37 degrees C). Anaerobic growth occurred with anthraquinone-2,6-disulphonate, fumarate and NO3 (-) as electron acceptor. The main respiratory quinone was MK-7. The predominant polar lipids were diphosphatidylglycerol and phosphatidylethanolamine. The major fatty acids (>5 %) were iso-C15:0 (43.1 %), anteiso-C15:0 (27.4 %) and iso-C16:0 (8.3 %). The DNA G + C content was 39.6 mol%. The phylogenetic analysis based on 16S rRNA gene sequences revealed that strain GSS08(T) formed a phyletic lineage with the type strain of Bacillus humi DSM 16318(T) with a high sequence similarity of 97.5 %, but it displayed low sequence similarity with other valid species in the genus Bacillus (<96.0 %). The DNA-DNA relatedness between strains GSS08(T) and B. humi DSM 16318(T) was 50.8 %. The results of phenotypic, chemotaxonomic and genotypic analyses clearly indicated that strain GSS08(T) represents a novel species, for which the name Bacillus nitroreducens sp. nov. is proposed. The type strain is GSS08(T) (=KCTC 33699(T) = MCCC 1K01091(T)). PMID- 26832131 TI - Temporal variability in trace metal solubility in a paddy soil not reflected in uptake by rice (Oryza sativa L.). AB - Alternating flooding and drainage conditions have a strong influence on redox chemistry and the solubility of trace metals in paddy soils. However, current knowledge of how the effects of water management on trace metal solubility are linked to trace metal uptake by rice plants over time is still limited. Here, a field-contaminated paddy soil was subjected to two flooding and drainage cycles in a pot experiment with two rice plant cultivars, exhibiting either high or low Cd accumulation characteristics. Flooding led to a strong vertical gradient in the redox potential (Eh). The pH and Mn, Fe, and dissolved organic carbon concentrations increased with decreasing Eh and vice versa. During flooding, trace metal solubility decreased markedly, probably due to sulfide mineral precipitation. Despite its low solubility, the Cd content in rice grains exceeded the food quality standards for both cultivars. Trace metal contents in different rice plant tissues (roots, stem, and leaves) increased at a constant rate during the first flooding and drainage cycle but decreased after reaching a maximum during the second cycle. As such, the high temporal variability in trace metal solubility was not reflected in trace metal uptake by rice plants over time. This might be due to the presence of aerobic conditions and a consequent higher trace metal solubility near the root surface, even during flooding. Trace metal solubility in the rhizosphere should be considered when linking water management to trace metal uptake by rice over time. PMID- 26832133 TI - Design and optimization of gastro-retentive microballoons for enhanced bioavailability of cinnarizine. AB - This study is focused on the design of gastro-retentive drug delivery system composed of hollow microspheres (microballoons) for the sustained delivery of cinnarizine (CIN). The microballoons (MBs) were prepared by the emulsion solvent diffusion method using cellulose acetate butyrate (CAB) as the hosting polymer and absolute ethanol (ETH) and dichloromethane (DCM) as solvents. A 3(3) full factorial experimental design was adopted to study the effect of different variables and to find an optimum formula with desired properties. Prepared microballoons showed high drug loading capacities and controlled release behaviour. The optimum formulation was chosen on the basis of achieving maximum values for both drug loading capacity and release efficiency as well as having suitable size. The optimized MB (MB-F21) was composed of 200 mg CIN and 400 mg CAB with a DCM/ETH ratio of 2:1. Scanning electron microscopy for the optimum formulation showed a spherical outline with internal porous structure. An in vivo study using human volunteers was performed by determination of CIN concentration in the plasma using the liquid chromatography-mass spectrometry (LC-MS) method. Results proved the superiority of the designed formulation over the market product Stuval(r) tablets in bioavailability parameters comprising T max as well as area under the plasma CIN concentration-time curve (AUC0-24 h) and AUC0 infinity values. Also, the significantly greater value of mean residence time (MRT) in case of MB-F21 indicates its higher gastric residence time and proves the advantages of micro-multiparticulate dosage forms over conventional one. PMID- 26832134 TI - The relationships between heart rate deceleration capacity and spectral indices of heart rate variability during different breathing frequencies. AB - PURPOSE: The frequency of breathing influences the spectral powers of heart rate variability (HRV) as well as the magnitudes of heart rate deceleration capacity (DC) and acceleration capacity (AC). We compared the strength of their relationships under different breathing frequencies. METHODS: We studied 14 healthy young adults who breathed spontaneously and controlled their breathing rates to 0.1, 0.2, 0.3 and 0.4 Hz in a supine position. A 5-min R-R interval time series without movement artefacts or ectopic beats was obtained for each study period. Spectral indices were defined as the square roots of spectral powers in the very low frequency (0.01-0.04 Hz), low frequency (0.04-0.15 Hz), high frequency (0.15-0.4 Hz) and respiratory frequency bands. We also combined these frequency bands into LHF (0.04-0.4 Hz) and VLHF (0.01-0.4 Hz). DC and AC were obtained using phase rectified signal averaging. RESULTS: DC and AC were significantly correlated with all indices of HRV. The within-subject correlation coefficients for the LHF index had the greatest absolute values (0.953 and 0.919, respectively). DC and AC had different strength of relationships with the LHF index, but became comparable (0.954 vs. -0.943) when the data obtained under 0.1-Hz breathing were excluded. CONCLUSION: DC is strongly correlated with the spectral index of the LHF band, indicating that they are controlled by similar influences under the conditions used in this study. AC is less related to the LHF index due to the fact that its magnitude deceases during 0.1-Hz breathing. PMID- 26832135 TI - A Genetic Risk Score Is Associated with Weight Loss Following Roux-en Y Gastric Bypass Surgery. AB - BACKGROUND: Currently, Roux-en Y gastric bypass (RYGB) is the most efficient therapy for severe obesity. Weight loss after surgery is, however, highly variable and genetically influenced. Genome-wide association studies have identified several single nucleotide polymorphisms (SNP) associated with body mass index (BMI) and waist-hip ratio (WHR). We aimed to identify two genetic risk scores (GRS) composed of weighted BMI and WHR-associated SNPs to estimate their impact on excess BMI loss (EBMIL) after RYGB surgery. METHODS: Two hundred and thirty-eight obese patients (BMI 45.1 +/- 6.2 kg/m(2), 74 % women), who underwent RYGB, were genotyped for 35 BMI and WHR-associated SNPs and were followed up after 2 years. SNPs with high impact on post-surgical weight loss were filtered out using a random forest model. The filtered SNPs were combined into a GRS and analyzed in a linear regression model. RESULTS: An up to 11 % lower EBMIL with higher risk score was estimated for two GRS models (P = 0.026 resp. P = 0.021) composed of seven BMI-associated SNPs (closest genes: MC4R, TMEM160, PTBP2, NUDT3, TFAP2B, ZNF608, MAP2K5, GNPDA2, and MTCH2) and of three WHR-associated SNPs (closest genes: HOXC13, LYPLAL1, and DNM3-PIGC). Patients within the lowest GRS quartile had higher EBMIL compared to patients within the other three quartiles in both models. CONCLUSIONS: We identified two GRSs composed of BMI and WHR-associated SNPs with significant impact on weight loss after RYGB surgery using random forest analysis as a SNP selection tool. The GRS may be useful to pre-surgically evaluate the risks for patients undergoing RYGB surgery. PMID- 26832136 TI - Laparoscopic Sleeve Gastrectomy with Intraoperative Endoscopic Guidance: the Importance of This Technique. PMID- 26832137 TI - Deciphering the Role of microRNAs in Regulation of Immune Surveillance, Self Tolerance and Allograft Transplant Outcome. AB - MicroRNAs are small non-coding RNAs that can modulate gene expression at posttranscriptional level, and they participate in almost all important biological processes. Immune system is elaborately regulated to maintain the equilibrium between immunity and tolerance. Recent studies have revealed significant functions of microRNAs in the maintenance of immune homeostasis using both cell and transgenic mouse models. In collaboration with various transcriptional factors and cytokines, microRNAs constitute an effective and flexible regulatory network governing the development and activation of immune cells; as well as maintenance of immune tolerance. In this review, microRNAs involved in T cell development, proliferation, and lineage differentiation will be summarized. Based on current knowledge, the function of microRNAs in establishing and maintaining immune tolerance will also be discussed in relation to determining the outcome of allograft transplantation. PMID- 26832138 TI - Recent Strategies Combining Biomaterials and Stem Cells for Bone, Liver and Skin Regeneration. AB - This review is focused on the combination of biomaterials with stem cells as a promising strategy for bone, liver and skin regeneration. At first, we describe stem cell-based constructs for bone tissue engineering with special attention to recent advanced approaches based on the use of biomaterial scaffolds with renewable stem cells that have been used for bone regeneration. We illustrate the strategies to improve liver regeneration by using liver stem cells and biomaterials and/or devices as therapeutic approaches. In particular, examples of biomaterials in combination with other technologies are presented since they allow the differentiation of stem cells in hepatocytes. After a description of the role and the benefit of MSCs in wound repair and in skin substitutes we highlight the suitability of biomaterials in guiding stem cell differentiation for skin regeneration and cutaneous repair in both chronic and acute wounds. Finally, an overview of the types of bioreactors that have been developed for the differentiation of stem cells and are currently in use, is also provided. The examples of engineered microenvironments reported in this review indicate that a detailed understanding of the various factors and mechanisms that control the behavior of stem cells in vivo has provided useful information for the development of advanced bioartificial systems able to control cell fate. PMID- 26832139 TI - Possible Role of Cancer Stem Cells in Colorectal Cancer Metastasizing to the Liver. AB - Colorectal cancer (CRC) is one of the most common cancers in the world. In recent decades, drug therapy and surgery have not achieved satisfactory results in curing CRC. The identification of cancer stem cells (CSCs) has provided a possible mechanistic explanation of CRC growth and metastasis. Traditional chemotherapy targets rapidly dividing cells, and since the CSCs can escape these therapies and become circulating cells, CSCs may be responsible for cancer relapse and metastasis. A better understanding of the roles of CSCs in the pathogenesis of primary CRC and its metastasis, as well as how these CSCs are regulated at the molecular level, is of paramount importance. In this review, we summarize the current understanding of the role of colorectal CSCs in CRC liver metastasis, and provide some insights on the potential implication of colorectal CSCs to better design therapeutic regimens and prevent CRC metastasis. PMID- 26832140 TI - Double faced role of human mesenchymal stem cells and their role challenges in cancer therapy. AB - Human mesenchymal stem cells (hMSCs) are multipotent non-hematopoietic precursor cells with the ability to differentiate into several tissue types. The use of hMSCs has gained significant importance in cancer therapies as well as a large number of degenerative disease therapies due to their homing abilities. However, these cells may undergo spontaneous transformation leading to them bypassing naturally built-in cell controls that could lead to senescence and carcinogenesis. Therefore, although MSCs have great potential for cancer therapy, they also risk the development of cancer, which provides them with double-faced characteristics for both cancer development and therapy. The potential use of hMSCs in therapeutics from the aspect of in vitro expansion of hMSCs and telomere dynamic is discussed. PMID- 26832141 TI - Phenotypic diversity and correlation between white-opaque switching and the CAI microsatellite locus in Candida albicans. AB - Candida albicans is a commensal fungal pathogen that is often found as part of the human microbial flora. The aim of the present study was to establish a relationship between diverse genotypes and phenotypes of clinical isolates of C. albicans. Totally 231 clinical isolates were collected and used for genotyping and phenotypic switching analysis. Based on the microsatellite locus (CAI) genotyping assay, 65 different genotypes were identified, and some dominant types were found in certain human niches. For example, the genotypes of 30-44 and 30-45 were enriched in vaginal infection samples. C. albicans has a number of morphological forms including the single-celled yeasts, multicellular filaments, white, and opaque cell types. The relationship between the CAI genotype and the ability to undergo phenotypic switching was examined in the clinical isolates. We found that the strains with longer CAA/G repeats in both alleles of the CAI locus were more opaque competent. We also discovered that some MTL heterozygous (a/alpha) isolates could undergo white-opaque switching when grown on regular culture medium (containing glucose as the sole carbon source). Our study establishes a link between phenotypic switching and genotypes of the CAI microsatellite locus in clinical isolates of C. albicans. PMID- 26832142 TI - Genome-wide bioinformatics analysis of steroid metabolism-associated genes in Nocardioides simplex VKM Ac-2033D. AB - Actinobacteria comprise diverse groups of bacteria capable of full degradation, or modification of different steroid compounds. Steroid catabolism has been characterized best for the representatives of suborder Corynebacterineae, such as Mycobacteria, Rhodococcus and Gordonia, with high content of mycolic acids in the cell envelope, while it is poorly understood for other steroid-transforming actinobacteria, such as representatives of Nocardioides genus belonging to suborder Propionibacterineae. Nocardioides simplex VKM Ac-2033D is an important biotechnological strain which is known for its ability to introduce ?(1)-double bond in various 1(2)-saturated 3-ketosteroids, and perform convertion of 3beta hydroxy-5-ene steroids to 3-oxo-4-ene steroids, hydrolysis of acetylated steroids, reduction of carbonyl groups at C-17 and C-20 of androstanes and pregnanes, respectively. The strain is also capable of utilizing cholesterol and phytosterol as carbon and energy sources. In this study, a comprehensive bioinformatics genome-wide screening was carried out to predict genes related to steroid metabolism in this organism, their clustering and possible regulation. The predicted operon structure and number of candidate gene copies paralogs have been estimated. Binding sites of steroid catabolism regulators KstR and KstR2 specified for N. simplex VKM Ac-2033D have been calculated de novo. Most of the candidate genes grouped within three main clusters, one of the predicted clusters having no analogs in other actinobacteria studied so far. The results offer a base for further functional studies, expand the understanding of steroid catabolism by actinobacteria, and will contribute to modifying of metabolic pathways in order to generate effective biocatalysts capable of producing valuable bioactive steroids. PMID- 26832143 TI - Cognitive impairment and dependence of patients with diabetes older than 65 years old in an urban area (DERIVA study). AB - BACKGROUND: We analyzed the associations between diabetes and cognitive impairment (CI) and dependence in a population of patients 65 years or older. METHODS: Cross-sectional study. We randomly selected 311 participants over the age of 65 living in an urban area of Spain. The mean age of the cohort was 75.89 +/- 7.12 years, and 69 of the individuals (22.2%) had diabetes. Two questionnaires were used to assess cognitive performance (MMSE and Seven Minute Screen Test), and two assessments were used to evaluate patient dependence (Barthel Index and Lawton-Brody Index). Clinical information and sociodemographic data were also gathered. RESULTS: Nearly one quarter of patients with diabetes (21.7%) lived alone. Diabetic patients were more sedentary (p = .033) than non diabetic patients. Roughly one sixth (15.3%) of the diabetics and 10.1% of the non-diabetics were depressed (p = .332). CI was present in 26.1% of the diabetics and 14.5% of non-diabetics (p = .029). Diabetic patients had a MMSE score that was significantly worse than non-diabetics (24.88 +/- 4.74 vs 26.05 +/- 4.03; p <.05), but no differences were found in the Seven Minute Screen Test. Logistic regressions revealed that the presence of diabetes was independently associated with CI (adjusted for age, gender, years of education, sedentary lifestyle, body mass index, diastolic blood pressure, cholesterol, and depression (OR = 2.940, p = .013). Patients with diabetes showed greater dependence, as measured by the Barthel Index (p = .03) and Lawton-Brody Index (p <.01). Nevertheless, when dependence (dependence or not dependence for each questionnaire) used as a dependent variable in the logistic regression analyses, no significant association with diabetes was found, after adjusting for confounding variables. CONCLUSIONS: Diabetic patients over the age of 65 are more likely to present CI but not dependence. These findings support the need to include both a functional and cognitive assessment as necessary components in a standard evaluation in both clinical guides and randomized trials of therapeutic interventions in patients with diabetes. PMID- 26832144 TI - Improving the identification of priority populations to increase hepatitis B testing rates, 2012. AB - BACKGROUND: It is estimated that over 40 % of the 218,000 people with chronic hepatitis B (CHB) in Australia in 2011 are undiagnosed. A disproportionate number of those with undiagnosed infection were born in the Asia-Pacific region. Undiagnosed CHB can lead to ongoing transmission and late diagnosis limits opportunities to prevent progression to hepatocellular carcinoma (HCC) and cirrhosis. Strategies are needed to increase testing for hepatitis B virus (HBV) (including culturally and linguistically diverse communities, Aboriginal and/or Torres Strait Islander (Indigenous) people and people who inject drugs). General practitioners (GPs) have a vital role in increasing HBV testing and the timely diagnosis CHB. This paper describes the impact of a GP-based screening intervention to improve CHB diagnosis among priority populations in Melbourne, Australia. METHODS: A non-randomised, pre-post intervention study was conducted between 2012 and 2013 with three general practices in Melbourne, Australia. Using clinic electronic health records three priority populations known to be at increased CHB risk in Australia (1: Asian-born patients or patients of Asian ethnicity living in Australia; 2: Indigenous people; or 3): people with a history of injecting drugs were identified and their HBV status recorded. A random sample were then invited to attend their GP for HBV testing and/or vaccination. Baseline and follow-up electronic data collection identified patients that subsequently had a consultation and HBV screening test and/or vaccination. RESULTS: From a total of 33,297 active patients, 2674 (8 %) were identified as a priority population at baseline; 2275 (85.1 %) of these patients had unknown HBV status from which 338 (14.0 %) were randomly sampled. One-fifth (n = 73, 21.6 %) of sampled patients subsequently had a GP consultation during the study period; only four people (5.5 %) were subsequently tested for HBV (CHB detected in n = 1) and none were vaccinated against HBV. CONCLUSION: CHB infection is an important long term health issue in Australia and strategies to increase appropriate and timely testing are required. The study was effective at identifying whether Asian-born patients and patients of Asian had been tested or vaccinated for HBV; however the intervention was not effective at increasing HBV testing. PMID- 26832145 TI - Methodological Challenges to Economic Evaluations of Vaccines: Is a Common Approach Still Possible? AB - Economic evaluation of vaccination is a key tool to inform effective spending on vaccines. However, many evaluations have been criticised for failing to capture features of vaccines which are relevant to decision makers. These include broader societal benefits (such as improved educational achievement, economic growth and political stability), reduced health disparities, medical innovation, reduced hospital beds pressures, greater peace of mind and synergies in economic benefits with non-vaccine interventions. Also, the fiscal implications of vaccination programmes are not always made explicit. Alternative methodological frameworks have been proposed to better capture these benefits. However, any broadening of the methodology for economic evaluation must also involve evaluations of non vaccine interventions, and hence may not always benefit vaccines given a fixed health-care budget. The scope of an economic evaluation must consider the budget from which vaccines are funded, and the decision-maker's stated aims for that spending to achieve. PMID- 26832146 TI - The Urolift System for the Treatment of Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia: A NICE Medical Technology Guidance. AB - As part of its Medical Technologies Evaluation Programme (MTEP), the National Institute for Health and Care Excellence (NICE) invited Neotract (manufacturer) to submit clinical and economic evidence for their prostatic urethral lift device, Urolift, for the relief of lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS BPH). The Urolift System uses implants to retract the prostatic lobe away from the urethral lumen. The clinical evidence used in the manufacturer's submission shows that Urolift is effective for the treatment of BPH. Urolift delivers a weighted mean International Prostate Symptom Score (IPSS) improvement of between 9.22 and 11.82 points. These Urolift improvements are greater than a published 'marked improvement' in IPSS score of 8.80. Comparison with randomised controlled trials (RCTs) of TURP (Transurethral Resection of Prostate) and HoLEP (Holmium Laser Enucleation of Prostate) show that Urolift does not yield better clinical outcomes from baseline compared to TURP and HoLEP in terms of IPSS, QoL (Quality of Life) and Qmax (maximum urinary flow). However, Urolift appears to have the advantage in terms of minimal and mild complications, and this may be of interest to patients and urologists. The economic case for Urolift was made using a very detailed and thorough de novo cost model. The base case posed by the manufacturer placed Urolift at almost cost neutral (L3 cost incurring, based on 2014 prices) compared to TURP, and L418 cost incurring compared to HoLEP. In an additional scenario comparing day-case Urolift with in-patient TURP, the estimated per-patient savings with Urolift were L286 compared with monopolar TURP (mTURP) and L159 compared with bipolar TURP (BiTURP). NICE guidance MTG26 recommends that the case for adoption of Urolift was supported by the evidence, when implemented in a day-case setting. PMID- 26832147 TI - Diagnostic accuracy of peripheral venous lactate and the 2009 WHO warning signs for identifying severe dengue in Thai adults: a prospective observational study. AB - BACKGROUND: Dengue is the most common mosquito-borne viral disease in humans. However, the sensitivities of warning signs (WSs) for identifying severe dengue in adults are low, and the utility of lactate levels for identifying severe dengue in adults has not been verified. Therefore, we aimed to evaluate the diagnostic accuracy of using peripheral venous lactate levels (PVL), as well as WSs established by the World Health Organization, for identifying severe dengue. METHODS: We prospectively evaluated individuals hospitalized for dengue who were admitted to the Hospital for Tropical Diseases in Thailand between May 2013 and January 2015. Blood samples to evaluate PVL levels were collected at admission and every 24 h until the patient exhibited a body temperature of <37.8 degrees C for at least 24 h. Data were recorded on a pre-defined case report form, including baseline characteristics, clinical parameters, and laboratory findings. RESULTS: Among 125 patients with confirmed dengue, 105 (84.0%) patients had non severe dengue, and 20 (16.0%) patients had severe dengue. The presence of clinical fluid accumulation as a WS provided high sensitivity (75.0%, 95% confidence interval [CI]: 50.9-91.3%) and specificity (90.5%, 95% CI: 83.2 95.3%). The PVL level at admission was used to evaluate its diagnostic value, and receiver operating characteristic curve analysis revealed an area under the curve of 0.84 for identifying severe dengue. At the optimal cutoff value (PVL: 2.5 mmol/L), the sensitivity and specificity were 65.0% (95% CI: 40.8-84.6%) and 96.2% (95% CI: 90.5-99.0%), respectively. A combined biomarker comprising clinical fluid accumulation and/or PVL of >=2.5 mmol/L provided the maximum diagnostic accuracy for identifying severe dengue, with a sensitivity of 90.0% (95% CI: 68.3-98.8%) and a specificity of 87.6% (95% CI: 79.8-93.2%). CONCLUSIONS: Clinical fluid accumulation and/or PVL may be used as a diagnostic biomarker of severe dengue among adults. This biomarker may facilitate early recognition and timely treatment of patients with severe dengue, which may reduce dengue-related mortality and hospital burden. PMID- 26832148 TI - Does cartilage volume measurement or radiographic osteoarthritis at baseline independently predict ten-year cartilage volume loss? AB - BACKGROUND: The aim of this study was to examine whether cartilage volume as measured by MRI and radiographic osteoarthritis (OA) at baseline predict cartilage volume loss over ten years independent of each other and other structural co-pathologies. METHODS: 219 participants [mean-age 45(26-61); 57 % female] were studied at baseline and ten years. Approximately half were the adult offspring of subjects who underwent knee replacement for OA and the remainder were randomly selected controls. Joint space narrowing (JSN) and osteophytes were assessed on radiographs and cartilage volume (tibiofemoral), cartilage defects, bone marrow lesions and meniscal tears/extrusion were assessed on MRI. RESULTS: Mean absolute and percentage per annum cartilage volume loss was 1284 mm(3) and 1.91 % respectively in the medial compartment and 1007 mm(3) and 1.38 % respectively in the lateral compartment. Higher baseline tibiofemoral cartilage volume was independently associated with greater absolute cartilage volume loss in both medial (beta(95 % CI) = -300 (-399,-200)) and lateral (beta = -338 (-443, 233)) compartments and percentage per annum loss in the lateral compartment(beta = -0.15 (-0.29, -0.01)). Baseline JSN and osteophytes were associated with cartilage volume loss in the univariable analysis, however these associations did not persist after adjustment for other structural co-pathologies. CONCLUSION: Cross-sectional cartilage volume measurement independently predicts cartilage volume loss over 10 years and can be used to identify fast progressors in clinical trials. Radiographic JSN and osteophytes on the other hand are a reflection of other co-pathologies assessed on MRI and do not independently predict cartilage volume loss over 10 years. PMID- 26832150 TI - Risk of adverse pregnancy outcomes in women with periodontal disease and the effectiveness of interventions in decreasing this risk: protocol for systematic overview of systematic reviews. AB - BACKGROUND: Periodontal disease is an inflammatory disease of the tissues supporting the teeth. Women who have periodontal disease while pregnant may be at risk of adverse pregnancy outcomes. Although the association between periodontal disease and adverse pregnancy outcomes has been addressed in a considerable number of systematic reviews and meta-analyses, there are important differences in the conclusions of these reviews. Systematic reviews assessing the effectivity of various therapeutic interventions to treat periodontal disease during pregnancy to try and reduce adverse pregnancy outcomes have also arrived at different conclusions. We aim to provide a systematic overview of systematic reviews comparing the frequency of adverse pregnancy outcomes between women with and without periodontal disease and/or evaluating the effect of preventive and therapeutic interventions for periodontal disease before or during pregnancy on adverse pregnancy outcomes. METHODS: We will include systematic reviews reporting on studies comparing adverse pregnancy outcomes: (i) between women with or without periodontal disease before (<6 months) or during pregnancy and/or (ii) according to preventive or therapeutic interventions for periodontal disease. Eligible interventions include (combinations of) the following: oral hygiene education, use of antibiotics, subgingival scaling, and root planing. For preventive and/or therapeutic reviews, the following comparisons will be considered: no intervention, a placebo intervention, or an alternative intervention. Our primary adverse pregnancy outcomes of interests are maternal mortality, preterm delivery, and perinatal mortality. Two reviewers will independently identify eligible published and unpublished systematic reviews from six electronic databases and using hand searching of reference lists and citations. Data items extracted from included systematic reviews are based on the Cochrane Effective Practice and Organization of Care checklist and the preferred reporting items for systematic review and meta-analysis (PRISMA) statement. In our narrative data synthesis, we will consider risk of bias of individual reviews, focusing mainly on the conclusions of the highest quality reviews using the assessment of multiple systematic reviews (AMSTAR) checklist. Disagreements during search, selection, data extraction, and risk of bias assessment will be resolved through discussion and/or consultation of a third reviewer. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015030132. PMID- 26832149 TI - Vitamin B12 concentrations in pregnant Colombian women: analysis of nationwide data 2010. AB - BACKGROUND: Vitamin B12 deficiency is associated with many adverse health outcomes and is highly prevalent worldwide. The present study assesses the prevalence and socio-demographic factors associated with vitamin B12 deficiency in a representative sample of pregnant women in Colombia. METHOD: We used data from the cross-sectional, nationally representative survey (ENSIN, 2010). A total of 1.781, (13-49 years old) pregnant women were enrolled. Serum Vitamin B12 a concentration was determined by chemiluminescence and sociodemographic date was assessed by computer-assisted personal interview technology. Multivariate analyses using unordered multinomial logistic regression models were conducted in the main analysis. RESULTS: Vitamin B12 concentrations ranged from 45 to 1000 pg/mL (mean 299.2 pg/mL, 95% CI 290.6 to 303.7 pg/mL). A total of 18.6% of pregnant women had vitamin B12 concentrations below 200 pg/mL and 41.3% had concentrations between 200 and 300 pg/mL. Being of indigenous ethnicity, living in the east and living in a rural area showed the lowest mean values (273.2 pg/mL, 270.8 pg/mL and 290.1 pg/mL, respectively). The multivariate logistic regression shows that pregnant women belonging to the indigenous ethnic group OR 2.2, (95% CI 1.1 to 4.3), living in the pacific region (west) OR 4.4, (95% CI 2.8 to 6.9), or national territories (south) OR 2.3, (95% CI 1.4 to 3.7) were associated with a higher probability of serum vitamin B12 deficiency. CONCLUSION: The prevalence of vitamin B12 deficiency in Colombian pregnant women is substantial. Factors associated with depletion among pregnant women should be considered for future interventions in countries experiencing nutritional transition. PMID- 26832151 TI - MicroRNA-505 functions as a tumor suppressor in endometrial cancer by targeting TGF-alpha. AB - BACKGROUND: Endometrial carcinoma (EC) is one of the most lethal gynecologic cancers. Patients frequently have regional or distant metastasis at diagnosis. MicroRNAs are small non-coding RNAs that participate in numerous biological processes. Recent studies have demonstrated that miR-505 is associated with several types of cancer; however, the expression and function of miR-505 have not been investigated in EC. METHODS: miR-505 expression in normal endometrial tissue, endometrial carcinomas were quantified by Quantitative reverse transcription PCR. The endometrial carcinoma cell lines HEC-1B and Ishikawa were each transfected with miR-505 or scrambled mimics, after which cell phenotype and expression of relevant molecules were assayed. Dual-luciferase reporter assay and a xenograft mouse model were used to examine miR-505 and its target gene TGF alpha. RESULTS: RT-PCR results demonstrated that miR-505 was significantly downregulated in human EC tissues compared to normal endometrial tissues. Besides, miR-505 expression was negatively associated with FIGO stage (stage I-II vs. III-IV), and lymph node metastasis (negative vs. positive). In vitro, overexpression of miR-505 significantly suppressed EC cell proliferation, increased apoptosis and reduced migratory and invasive activity. A miR-505 binding site was identified in the 3' untranslated region of TGF-alpha mRNA (TGFA) using miRNA target-detecting software; a dual luciferase reporter assay confirmed that miR-505 directly targets and regulates TGFA. RT-PCR and Western blotting results indicated that overexpressing miR-505 reduced the expression of TGF-alpha and the TGF-alpha-regulated proteins MMP2, MMP9, CDK2, while induced Bax and cleaved-PARP expression in EC cells. In vivo, overexpression of miR-505 reduced the tumorigenicity and inhibited the growth of xenograft tumors in a mouse model of EC. CONCLUSIONS: Taken together, this study demonstrates that miR 505 acts as tumor suppressor in EC by regulating TGF-alpha. PMID- 26832152 TI - High cost enhances cooperation through the interplay between evolution and self organisation. AB - BACKGROUND: Cooperation is ubiquitous in biological systems, yet its evolution is a long lasting evolutionary problem. A general and intuitive result from theoretical models of cooperative behaviour is that cooperation decreases when its costs are higher, because selfish individuals gain selective advantage. RESULTS: Contrary to this intuition, we show that cooperation can increase with higher costs. We analyse a minimal model where individuals live on a lattice and evolve the degree of cooperation. We find that a feedback establishes between the evolutionary dynamics of public good production and the spatial self-organisation of the population. The evolutionary dynamics lead to the speciation of a cooperative and a selfish lineage. The ensuing spatial self-organisation automatically diversifies the selection pressure on the two lineages. This enables selfish individuals to successfully invade cooperators at the expenses of their autonomous replication, and cooperators to increase public good production while expanding in the empty space left behind by cheaters. We show that this emergent feedback leads to higher degrees of cooperation when costs are higher. CONCLUSIONS: An emergent feedback between evolution and self-organisation leads to high degrees of cooperation at high costs, under simple and general conditions. We propose this as a general explanation for the evolution of cooperative behaviours under seemingly prohibitive conditions. PMID- 26832153 TI - Proteome diversification by genomic parasites. AB - Alu elements can integrate into human genes and lead to the generation of primate specific isoforms. A new study examines their contribution to the human proteome. PMID- 26832154 TI - Evaluation of treatments for sacroiliitis in spondyloarthropathy using the Spondyloarthritis Research Consortium Canada scoring system. AB - BACKGROUND: In this study, the Spondyloarthritis Research Consortium Canada (SPARCC) scoring method was used to compare treatment methods in patients with axial spondyloarthritis (SpA), a form of sacroiliitis. MRI abnormalities in bone marrow edema (BME) were compared before and after treatment in order to compare the efficacy of anti-TNF-alpha and DMARD, alone or in combination, as treatments for sacroiliitis. METHODS: Fifty-six Chinese patients with axial SpA (mean age 22.6 years) were recruited. Patients were divided into three groups according to different treatments (anti-TNF-alpha alone vs. DMARDs alone vs. combined anti-TNF alpha and DMARDs). MRI examinations were performed before and after treatment. The SPARCC score, clinically relevant AS Disease Activity (ASDAS) indices, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were analyzed. RESULTS: After treatment, ASDAS and SPARCC scores, ESR, and CRP were significantly improved (P < 0.05) in the anti-TNF-alpha monotherapy and combination groups; however, there were no statistically significant differences (P > 0.05) in clinical disease activity and radiological inflammation of sacroiliac joint (SIJ) in patients in the DMARDs alone group. SPARCC showed a correlation with ASDAS score pre-treatment, but not post-treatment. Furthermore, there were significant changes (P < 0.05) in these patients with axial SpA after only 3 months of treatment. Follow-up studies of patients who continued therapy for 4-6 months and 9-12 months revealed statistically significant differences from baseline (P < 0.05). CONCLUSIONS: SPARCC can be used to assess severity of disease pre-treatment. Anti-TNF-alpha treatment resulted in effective reduction of disease activity and BME of SIJ after 3 months of therapy. PMID- 26832155 TI - Severe complication during strabismus surgery. AB - CLINICAL CASE: A 4-year-old patient, who presented with an immediate orbital haematoma as a result of a subtenon injection of triamcinolone in the trochlear region of the right eye on finishing a surgical procedure for Brown's syndrome. After one week, when it could be examined better, the presence of a cherry red spot was observed due to the embolisation of the central artery of the retina by triamcinolone crystals. DISCUSSION: Triamcinolone is an anti-inflammatory drug currently used in Ophthalmology for the treatment of various conditions. Although exceptional, it has been described that its use may provoke embolisations due to the entry of the steroid into the circulation. PMID- 26832156 TI - Subfoveal choroidal thickness in eyes with diabetic macular oedema using swept source optical coherence tomography. AB - PURPOSE: To compare subfoveal choroidal thickness (GCSF) in patients with diabetic macular oedema (DMO) and healthy subjects using swept source optical coherence tomography (SS-OCT). METHOD: Cross-sectional study including 50 eyes of 36 patients with DMO, and 47 eyes of 34 patients as a control group. GCSF was measured in both groups, analysing between the eyes with DMO according to the type of oedema (predominantly cystic or diffuse). RESULTS: The study groups were homogeneous in terms of mean age (63.4 years for DMO and 62.65 years for controls; P=.36) and the mean axial length (23.21mm for DME and 23.53mm for controls; P=.06). A statistically significant reduction in the eye with DME GCSF compared to controls (P=.041, 222.9 vs. 192.82 MUm) was observed. No statistically significant differences were observed in the eyes with DMO with a predominantly cystic pattern and diffuse oedema (P=.13, 178.68 vs. 205.7 MUm). CONCLUSION: The GCSF in patients with DMO could be reduced. Future studies are needed to confirm these preliminary results. PMID- 26832157 TI - Does the patient's inherent rating tendency influence reported satisfaction scores and affect division ranking? AB - OBJECTIVE: To determine the impact of adjusting for rating tendency (RT) on patient satisfaction scores in a large teaching hospital and to assess the impact of adjustment on the ranking of divisions. DESIGN: Cross-sectional survey. SETTING: Large 2200-bed university teaching hospital. PARTICIPANTS: All adult patients hospitalized during a 1-month period in one of 20 medical divisions. INTERVENTION: None. MAIN OUTCOME MEASURES: Patient experience of care measured by the Picker Patient Experience questionnaire and RT scores. RESULTS: Problem scores were weakly but significantly associated with RT. Division ranking was slightly modified in RT adjusted models. Division ranking changed substantially in case-mix adjusted models. CONCLUSIONS: Adjusting patient self-reported problem scores for RT did impact ranking of divisions, although marginally. Further studies are needed to determine the impact of RT when comparing different institutions, particularly across inter-cultural settings, where the difference in RT may be more substantial. PMID- 26832158 TI - Author's response. PMID- 26832159 TI - Types and patterns of safety concerns in home care: client and family caregiver perspectives. AB - OBJECTIVE: Drawing on interviews with home care clients and their family caregivers, we sought to understand how these individuals conceptualize safety in the provision and receipt of home care, how they promote safety in the home space and how their safety concerns differ from those of home support workers. DESIGN: In-depth, semi-structured interviews were conducted with clients and family caregivers. The analysis included topic and analytical coding of participants' verbatim accounts. SETTING: Interviews were completed in British Columbia, Canada. PARTICIPANTS: Totally 82 clients and 55 caregivers participated. RESULTS: Clients and family caregivers identified three types of safety concerns: physical, spatial and interpersonal. These concerns are largely multi-dimensional and intersectional. We present a conceptual model of client and caregiver safety concerns. We also examine the factors that intensify and mitigate safety concerns in the home. CONCLUSIONS: In spite of safety concerns, clients and family caregivers overwhelmingly prefer to receive care in the home setting. Spatial and physical concerns are the most salient. The financial burden of creating a safe care space should not be the client's alone to bear. The conceptualization and promotion of safety in home care must recognize the roles, responsibilities and perspectives of all of the actors involved, including workers, clients and their caregivers. PMID- 26832160 TI - Prostate cancer: Case volume and improved outcomes across cancer care. PMID- 26832161 TI - Stones: Tolvaptan might prevent kidney stone formation. PMID- 26832162 TI - Prostate cancer: Fat attracts cancer cells. PMID- 26832163 TI - Kidney cancer: Sunitinib versus everolimus for non-clear-cell renal cell carcinoma. PMID- 26832164 TI - Bladder cancer: To be or NOTCH2 be? PMID- 26832166 TI - Prostate cancer: Enzalutamide is superior to bicalutamide for mCRPC. PMID- 26832165 TI - The role of the sexual partner in managing erectile dysfunction. AB - Erectile dysfunction (ED) has detrimental social and psychological effects on the quality of life of affected individuals and their sexual partners. When medical intervention is introduced to treat ED, physicians, nurses, and clinical educators should consider this disorder as a shared health problem for the men with ED and their sexual partners. New therapeutics such as phosphodiesterase-5 inhibitors improve erectile function in affected men, and the ultimate goal of medical intervention for ED should be achievement of a satisfactory sex life for couples engaged sexual relationships. Sexual partners of men with ED have an important role in its management and improvement in quality of sex life; therefore, they should be involved in assessment of, diagnosis, education, counselling, and choice of therapy. This sexual- partner-engaged approach might assist treatment and rehabilitation, helping the couples affected by ED to achieve a high-quality sex life. PMID- 26832167 TI - Prostate cancer: Immunotherapy with PPV effective. PMID- 26832168 TI - Labeling Sexual Victimization Experiences: The Role of Sexism, Rape Myth Acceptance, and Tolerance for Sexual Harassment. AB - This study investigated whether attitudinal variables, such as benevolent and hostile sexism toward men and women, female rape myth acceptance, and tolerance of sexual harassment are related to women labeling their sexual assault experiences as rape. In a sample of 276 female college students, 71 (25.7%) reported at least one experience that met the operational definition of rape, although only 46.5% of those women labeled the experience "rape." Benevolent sexism, tolerance of sexual harassment, and rape myth acceptance, but not hostile sexism, significantly predicted labeling of previous sexual assault experiences by the victims. Specifically, those with more benevolent sexist attitudes toward both men and women, greater rape myth acceptance, and more tolerant attitudes of sexual harassment were less likely to label their past sexual assault experience as rape. The results are discussed for their clinical and theoretical implications. PMID- 26832169 TI - The interaction of central nitrergic and GABAergic systems on food intake in neonatal layer-type chicks. AB - Most physiological behaviors such as food intake are controlled by the hypothalamus and its nuclei. It has been demonstrated that injection of the paraventricular nucleus of the hypothalamus with nitric oxide (NO) donors elicited changes in the concentration of some amino acids, including GABA. Also, central nitrergic and GABAergic systems are known to provide inputs to the paraventricular nucleus and are involved in food intake control. Therefore, the present study examines the probable interaction of central nitrergic and GABAergic systems on food intake in neonatal layer-type chicks. The results of this study showed that intracerebroventricular (ICV) injection of L-arginine (400 and 800 nmol), as a NO donor, significantly decreased food intake (P < 0.001), but ICV injection of Nomega-Nitro-L-arginine methyl ester (L-NAME) (200 and 400 nmol), a NO synthesis inhibitor, increased food intake (P < 0.001). In addition, the orexigenic effect of gaboxadol (0.2 ug), a GABAA agonist, was significantly attenuated in ICV co-injection of L-arginine (200 nmol) and gaboxadol (0.2 ug) (P < 0.001), but it was significantly amplified in ICV co-injection of L-NAME (100 nmol) and gaboxadol (0.2 ug) (P < 0.001). On the other hand, the orexigenic effect of baclofen (0.2 ug), a GABAB agonist, did not change in ICV co-injection of L-arginine (200 nmol) or L-NAME (100 nmol) with baclofen (0.2 ug) (P > 0.05). Also, the hypophagic effect of L-arginine (800 nmol) was significantly amplified in ICV co-injection of picrotoxin (0.5 ug), a GABAA antagonist, or CGP54626 (21 ng), a GABAB antagonist, with L-arginine (800 nmol) (P < 0.001). These results probably suggest an interaction of central nitrergic and GABAergic systems on food intake in neonatal layer-type chicks and GABAA receptors play a major role in this interaction. PMID- 26832170 TI - Creatine supplementation as a possible new therapeutic approach for fatty liver disease: early findings. AB - Over the last few years, consistent data have demonstrated that creatine (Cr) supplementation prevents the accumulation of fat in rat liver as well as the progression of fatty liver disease in different situations. Studies have demonstrated that Cr is effective and prevents fatty liver in high-fat and choline-deficient diets and in hepatoma cells in vitro. Because Cr synthesis is responsible for a considerable consumption of hepatic methyl groups, studies have tested the idea that Cr supplementation could modulate phospholipid formation and VLDL secretion. Studies have also demonstrated Cr is able to modulate the expression of key genes related to fatty acid oxidation in hepatocyte cell culture and in rat liver. However, to date, the mechanism by which Cr exerts protective effects against fatty liver is poorly understood. Therefore, the present review aims to summarize the studies involving the therapeutic use of Cr supplementation on fatty liver disease and to explore the mechanisms involved in one-carbon and fatty acid metabolism for the preventive effects of Cr supplementation on fat liver accumulation. Although a small number of studies have been conducted to date, we consider Cr as a new and promising therapeutic strategy to control fat accumulation in the liver as well as the progression of fatty liver disease. PMID- 26832171 TI - Characterization of aromatic aminotransferases from Ephedra sinica Stapf. AB - Ephedra sinica Stapf (Ephedraceae) is a broom-like shrub cultivated in arid regions of China, Korea and Japan. This plant accumulates large amounts of the ephedrine alkaloids in its aerial tissues. These analogs of amphetamine mimic the actions of adrenaline and stimulate the sympathetic nervous system. While much is known about their pharmacological properties, the mechanisms by which they are synthesized remain largely unknown. A functional genomics platform was established to investigate their biosynthesis. Candidate enzymes were obtained from an expressed sequence tag collection based on similarity to characterized enzymes with similar functions. Two aromatic aminotransferases, EsAroAT1 and EsAroAT2, were characterized. The results of quantitative reverse transcription polymerase chain reaction indicated that both genes are expressed in young stem tissue, where ephedrine alkaloids are synthesized, and in mature stem tissue. Nickel affinity-purified recombinant EsAroAT1 exhibited higher catalytic activity and was more homogeneous than EsAroAT2 as determined by size-exclusion chromatography. EsAroAT1 was highly active as a tyrosine aminotransferase with alpha-ketoglutarate followed by alpha-ketomethylthiobutyrate and very low activity with phenylpyruvate. In the reverse direction, catalytic efficiency was similar for the formation of all three aromatic amino acids using L-glutamate. Neither enzyme accepted putative intermediates in the ephedrine alkaloid biosynthetic pathway, S-phenylacetylcarbinol or 1-phenylpropane-1,2-dione, as substrates. PMID- 26832173 TI - Pediatric Quality Measures. PMID- 26832172 TI - Amino acids in the cultivation of mammalian cells. AB - Amino acids are crucial for the cultivation of mammalian cells. This importance of amino acids was realized soon after the development of the first cell lines, and a solution of a mixture of amino acids has been supplied to cultured cells ever since. The importance of amino acids is further pronounced in chemically defined mammalian cell culture media, making the consideration of their biological and chemical properties necessary. Amino acids concentrations have been traditionally adjusted to their cellular consumption rates. However, since changes in the metabolic equilibrium of amino acids can be caused by changes in extracellular concentrations, metabolomics in conjunction with flux balance analysis is being used in the development of culture media. The study of amino acid transporters is also gaining importance since they control the intracellular concentrations of these molecules and are influenced by conditions in cell culture media. A better understanding of the solubility, stability, dissolution kinetics, and interactions of these molecules is needed for an exploitation of these properties in the development of dry powdered chemically defined media for mammalian cells. Due to the complexity of these mixtures however, this has proven to be challenging. Studying amino acids in mammalian cell culture media will help provide a better understanding of how mammalian cells in culture interact with their environment. It would also provide insight into the chemical behavior of these molecules in solutions of complex mixtures, which is important in the understanding of the contribution of individual amino acids to protein structure. PMID- 26832174 TI - The extracellular matrix protein laminin-10 promotes blood-brain barrier repair after hypoxia and inflammation in vitro. AB - BACKGROUND: The blood-brain barrier (BBB) of the central nervous system (CNS) is essential for normal brain function. However, the loss of BBB integrity that occurs after ischaemic injury is associated with extracellular matrix (ECM) remodelling and inflammation, and contributes to poor outcome. ECM remodelling also contributes to BBB repair after injury, but the precise mechanisms and contribution of specific ECM molecules involved are unknown. Here, we investigated the mechanisms by which hypoxia and inflammation trigger loss of BBB integrity and tested the hypothesis ECM changes could contribute to BBB repair in vitro. METHODS: We used an in vitro model of the BBB, composed of primary rat brain endothelial cells grown on collagen (Col) I-, Col IV-, fibronectin (FN)-, laminin (LM) 8-, or LM10-coated tissue culture plates, either as a single monolayer culture or on Transwell(r) inserts above mixed glial cell cultures. Cultures were exposed to oxygen-glucose deprivation (OGD) and/or reoxygenation, in the absence or the presence of recombinant interleukin-1beta (IL-1beta). Cell adhesion to ECM molecules was assessed by cell attachment and cell spreading assays. BBB dysfunction was assessed by immunocytochemistry for tight junction proteins occludin and zona occludens-1 (ZO-1) and measurement of trans endothelial electrical resistance (TEER). Change in endothelial expression of ECM molecules was assessed by semi-quantitative RT-PCR. RESULTS: OGD and/or IL-1 induce dramatic changes associated with loss of BBB integrity, including cytoplasmic relocalisation of membrane-associated tight junction proteins occludin and ZO-1, cell swelling, and decreased TEER. OGD and IL-1 also induced gene expression of key ECM molecules associated with the BBB, including FN, Col IV, LM 8, and LM10. Importantly, we found that LM10, but not FN, Col IV, nor LM8, plays a key role in maintenance of BBB integrity and reversed most of the key hallmarks of BBB dysfunction induced by IL-1. CONCLUSIONS: Our data unravel new mechanisms of BBB dysfunction induced by hypoxia and inflammation and identify LM10 as a key ECM molecule involved in BBB repair after hypoxic injury and inflammation. PMID- 26832175 TI - Comparative Study of Core Needle Biopsy and Fine Needle Aspiration Cytology in Palpable Breast Lumps: Scenario in Developing Nations. AB - OBJECTIVE: The purpose of this study was to evaluate the utility of core needle biopsy as a diagnostic tool for palpable breast lumps in developing countries as compared to fine needle aspiration cytology. MATERIAL AND METHOD: All patients attending the surgery outpatient department with palpable breast lumps were subjected to fine needle aspiration cytology and core needle biopsy by the same operator in a single session. Fine needle aspiration cytology was performed by the standard technique. Core needle biopsy was done freehand using a 14G manual core biopsy needle. Reporting categories of the two techniques were taken from the standard National Health Service Breast Screening Programme criteria and were compared with the final histopathology results. RESULTS: A total of 107 patients underwent fine needle aspiration cytology and core needle biopsy simultaneously. Histopathology was available for 85 cases. Statistical analysis of fine needle aspiration cytology and core needle biopsy showed no significant difference between the diagnoses offered by core needle biopsy and histopathology while there was a significant difference between fine needle aspiration cytology and histopathology diagnoses. CONCLUSION: Core needle biopsy detected more breast carcinomas as compared to fine needle aspiration cytology with a sensitivity 95.83% as opposed to 64.58%. Though both the techniques were equally specific (100%), Core needle biopsy was able to correctly categorize borderline / inadequate lesions into definitely benign and malignant categories. We suggest that core needle biopsy should be preferred over fine needle aspiration cytology for the diagnosis of palpable breast lumps with fine needle aspiration cytology being reserved for definitely benign lesions. PMID- 26832176 TI - The Relation of Parafibromin Expression with Clinicopathological Factors in Invasive Breast Carcinomas. AB - OBJECTIVE: We aimed to find the relationship between parafibromin expression and clinicopathologic variables of breast carcinoma. MATERIAL AND METHOD: Ninety seven cases of invasive breast carcinoma diagnosed at our department between the years 2010-2013 were included in the study. The parafibromin expression state was compared with the estrogen receptor, progesterone receptor, cerbB2, Ki67 results, and the clinicopathological variables. RESULTS: Among 97 breast carcinoma cases, 66 (68%) were invasive ductal carcinoma. The average age was 54.3 (min:25, max:100), and the average tumor size was 31.1 mm (min:7, max:120). Lymph node metastasis was detected in 58% of the cases. Eleven were diagnosed with metastasis amongst 77 cases whose distant metastasis data could be reached. Eleven cases were lost due to breast carcinoma. As the tumor grade increased, the possibility of distant metastasis and lymph node metastasis increased as well (p=0.04, p=0.05, respectively). The mean follow-up duration of the cases was 26.6 +/- 9.8 (min. 6, max. 53) months, and there was no significant difference in survival between the other variables. Of the cases, 21.6% were negative, 9.3% were (+) positive, 11.3% were (++) positive and 57.7% were (+++) positive for parafibromin. It was found that there was an inverse correlation between the Ki67 proliferation index and lymph node metastasis and the parafibromin expression (p=0.018, p=0.029, respectively). CONCLUSION: We suggest that parafibromin may be a possible prognostic and predictive parameter for breast carcinomas. As the data on this matter in the literature is limited, it would be beneficial to investigate the matter and evaluate its relationship with survival in larger series. PMID- 26832177 TI - Twist Expression in Pleomorphic Adenoma, Adenoid Cystic Carcinoma and Mucoepidermoid Carcinoma of Salivary Glands. AB - OBJECTIVE: Twist is an important transcription factor that induces epithelial mesenchymal transition and therefore plays an important role in tumor progression. There are a few studies on Twist expression in salivary gland carcinomas. The aim of this study was to evaluate and compare the expression of Twist in the most common benign and malignant salivary gland tumors and to determine whether its expression was correlated with any tumor characteristics. MATERIAL AND METHOD: In this retrospective cross-sectional study, 45 cases including 11 cases of normal salivary gland, 12 pleomorphic adenomas, 12 adenoid cystic carcinomas and 10 mucoepidermoid carcinomas were enrolled. The mean and intensity of Twist expression were evaluated immunohistochemically and were compared using statistical analysis. RESULTS: The expression of Twist was higher in malignant salivary gland tumors in comparison with normal glands and benign tumors (p= 0.03). It was also higher in pleomorphic adenomas in comparison with normal tissue. Adenoid cystic carcinomas and mucoepidermoid carcinomas showed no significant difference in Twist expression (p= 0.50). There was no correlation with the size, stage or grade of tumor. CONCLUSION: The findings showed that Twist might play a role in the formation of salivary gland neoplasm and also may affect malignant transformation and tumoral invasion. The exact mechanism of this marker and the possibility of using it as a therapeutic target require further investigation. PMID- 26832178 TI - Comparative Study of Mast Cell Count in Oral Reactive Lesions and Its Association with Inflammation. AB - OBJECTIVE: Reactive hyperplastic lesions are one of the most common lesions of the oral cavity. Mast cells can be found in various oral lesions. However, the exact role of mast cells in oral reactive lesions is not fully understood. The aim of this study was to compare the mast cells count in various oral reactive lesions and to evaluate the correlation between the mast cells number and the intensity of inflammation. MATERIAL AND METHOD: This cross-sectional study was performed on 80 samples of oral reactive lesions including irritation fibroma, pyogenic granuloma, peripheral giant cell granuloma and peripheral ossifying fibroma (20 for each). Eight samples of normal oral mucosa were selected as the control group. To determine the mast cells count and the intensity of inflammation, Toluidine blue and Hematoxylin & Eosin staining was performed respectively. The data was analyzed with SPSS (V.21), Kruskal-Wallis, Tukey and Spearman's correlation coefficient tests. RESULTS: In this study, a significant increase in mast cells count was found in oral reactive lesions compared to normal oral mucosa (p < 0.001). Difference of mast cell count between irritation fibroma and the peripheral giant cell granuloma groups (p=0.023), peripheral ossifying fibroma and peripheral giant cell granuloma groups (p=0.001) was statistically significant. There was a significant correlation between mast cell count and the intensity of inflammation in the irritation fibroma and pyogenic granuloma groups. CONCLUSION: The finding of this study showed that mast cells count in peripheral ossifying fibroma and irritation fibroma were significantly higher than normal oral mucosa, so mast cells may have some role in the induction of fibrosis in oral reactive lesions. PMID- 26832179 TI - A Critical Appraisal of the Spectrum of Image Guided Fine Needle Aspiration Cytology: A Three Year Experience from a Tertiary Care Centre in Delhi. AB - OBJECTIVE: Image guided fine needle aspiration cytology (FNAC) is a safe, simple, rapid, cost effective and accurate modality in evaluation of deep seated lumps (abdominal, pelvic and intrathoracic masses) which are unapproachable by blind FNAC. In this study, a critical analysis of the utility of image guided FNAC in deep seated and otherwise inacessible mass lesions was carried out. MATERIAL AND METHOD: Fifty-four ultrasound (USG) or computed tomography (CT) guided FNACs from lumps at any location in the body, that is, thoracic, abdominal, pelvic etc over a period of 3 years (January 2012- December 2014) were included in the study. The most common site aspirated, the indications for a guided aspiration and the accuracy of aspiration cytology in comparison to the histological diagnosis were evaluated, wherever possible. RESULTS: Fifty-four image guided FNACs were performed (46 USG guided and 8 CT guided). Inconclusive, inflammatory, benign tumors, suspicious and malignant lesion rates were 5.6%, 29.6%, 11.1%, 5.6%, and 48.1%, respectively. The most common site was the liver (25.5%), followed by the thyroid (18.5%), lung (14.8%), gallbladder (11.1%), and lymph nodes (7.4%). Cytohistological correlation could be performed in 32 cases with a diagnostic accuracy of 100%. CONCLUSION: FNAC coupled with a diagnostic imaging technique such as USG or CT can improve the diagnostic yield and a definite diagnosis can be reached in most of the cases. PMID- 26832180 TI - Salivary Gland Tumors: A 15- year Report from Iran. AB - OBJECTIVE: The aim of this study was to document the clinicopathologic characteristic of salivary gland tumors in Tehran, Iran, over a 15-year period. MATERIAL AND METHOD: A retrospective study was conducted on salivary gland tumors diagnosed at two pathology centers of Shahid Beheshti University of Medical Sciences from March 2000 to March 2015. Patient age, sex, tumor site and frequency, as well as clinical and radiographic features and histopathologic diagnosis constituted the main analysis outcome measures. RESULTS: Of the 45429 biopsies conducted over 15 years, 6065 (13.3%) cases were oral and maxillofacial lesions and 937 (15.4%) of these had tumoral diagnoses. Of the 937 tumoral cases, 184 (19.6%) were salivary gland tumors and among 184 cases, 65 (35.3%) were benign and 119 (64.7%) were malignant. Pleomorphic adenoma was the most frequently occurring tumor, comprising 32.6% of all tumors, followed by mucoepidermoid carcinoma (27.1%) and adenoid cystic carcinoma (22.2%). Tumors were frequently reported in minor salivary glands (75%), particularly in the palate with 89 (48.4%) cases. The peak ages of incidence were the fourth and sixth decades of life. Malignant salivary gland tumors showed a predilection for females (72.9%), which was statistically significant (P < 0.01). CONCLUSION: The data presented herein are similar to previously published reports in other countries and other areas of Iran. However, some differences were observed in our study, such as higher overall frequency, a lower mean age of patients with malignant tumors, and the particular sites of involvement. These differences can be attributed to racial factors, the pathology centers of sample collection, and the duration of the studies. PMID- 26832181 TI - Natural Killer-Like T-Cell Lymphoma Localized to the Terminal Ileum: Case Report. AB - Intestinal intraepithelial lymphocytes are non-organized lymphoid populations that are composed of heterogeneous subsets with diverse ontogeny and phenotypes, and the differential diagnosis is crucial. A 43-year-old male patient underwent an emergency laparotomy due to a perforated mass of the terminal ileum. A right hemicolectomy plus small bowel resection was performed. Histopathological examination showed medium to large cells with vesicular nuclei, including marked nucleoli with large, colorless cytoplasm. No signs of celiac disease were found in the adjacent mucosa. The tumor cells were immunohistochemically CD45+, CD3+, CD4+, CD8+, CD56+, Pan-Cytokeratin-, CD20-, CD79a-, CD5- and CD30-. Endomysial antibody and antigliadin antibody, IgM and IgG tests; and anti-Ebstein Barr virus latent membrane protein all proved negative. Finally, the histopathological diagnosis of tumor mass was natural killer-like T-cell lymphoma. Primary intestinal cytotoxic natural killer-like T-cell lymphoma is a rare entity, which is difficult to distinguish from other T-cell lymphomas. In addition to microscopic evaluation, immunohistochemical analysis and serological tests are essential to reach a definitive diagnosis. PMID- 26832182 TI - Broad Ligament Perivascular Epithelioid Cell Tumor (PEComa) of Uncertain Malignant Potential. AB - PEComas are uncommon mesenchymal tumors often involving the pelvic organs. They have an unpredictable behavior. Accurate diagnosis and long-term follow-up is therefore essential in these patients. We report this case of PEComa of uncertain malignant potential in an unusual location with excellent prognosis. PMID- 26832183 TI - [A Gossypiboma (Textiloma) Mimicking a Gastrointestinal Stromal Tumor: A Case Report]. AB - Gossypiboma (textiloma) is a rare but preventable complication occurring due to oblivion of the surgical material during an operation that carries important diagnostic difficulties as well as high morbidity and mortality risks. The actual incidence is unknown because of its medicolegal aspects. Our case is a 36-years old female patient, who had a caesarean section two years ago in another center. Clinical examination and radiological investigations gave the impression of "gastrointestinal stromal tumor" and the surgically taken out mass was sent to our pathology department. The case was reported as a "gossypiboma"' and presented here to emphasize the diagnostic difficulties in the preoperative period, the life-threatening nature of the condition and as well as the rarity of the reported cases. PMID- 26832184 TI - A Problematic Case of Unclassified Multicystic Biliary Tumor with Adenofibroma Features. PMID- 26832185 TI - Diagnostic Disputes Regarding Atypical Melanocytic Lesions can be Solved by Using the Term MELTUMP. PMID- 26832186 TI - Inflammatory Mediators and Clinical Outcome in Patients With Advanced Heart Failure Receiving Cardiac Resynchronization Therapy. AB - Expression of different cytokines and growth factors after myocardial injury has been associated with fibroplasia and dilatation versus reverse remodeling and myocardial repair. Specifically, the proinflammatory/fibrotic mediators: interleukin (IL)-6, epidermal growth factor, and fibroblast growth factor (FGF)-2 cause fibroplasia, whereas reparative cytokines including: IL-1alpha, IL-1beta, IL-4, and IL-13 can limit fibrosis. In appropriate patients, cardiac resynchronization therapy (CRT) reverses cardiomyopathy and improves outcome. However, a significant proportion will not respond to this therapy. We conducted this study to assess the association of proinflammatory/fibrotic and/or reparative immune response mediators at baseline with outcome after CRT. In the multicenter RISK study, plasma samples were collected prospectively before CRT implantation. Plasma IL-6, epidermal growth factor, FGF-2, IL-1alpha, IL-1beta, IL-4, and IL-13 were evaluated by Luminex technology. The primary outcome was predefined as freedom from heart failure hospitalization or death and a decrease in echocardiographic end-systolic volume of >15% at 12 months. To determine associations with the outcome, multivariate logistic regression models including baseline clinical characteristics and the specific cytokines and growth factors were constructed. On multivariate analysis of 257 patients, detectable reparative cytokine IL-13 was significantly associated with the primary outcome (odds ratio 3.79; 95% CI 2.10 to 6.82, p <0.0001). In contrast, detectable proinflammatory/fibrotic growth factor FGF-2 was negatively associated (odds ratio 0.31; 95% CI, 0.14 to 0.68; p = 0.004). In conclusion, in CRT recipients, baseline levels of inflammatory mediators affecting cardiac fibrosis versus repair were associated with subsequent clinical outcome. PMID- 26832187 TI - Association between hip morphology and prevalence, clinical severity and progression of hip osteoarthritis over 3 years: The knee and hip osteoarthritis long-term assessment cohort results. AB - OBJECTIVE: To assess the effects of variations in hip morphology on prevalence, clinical severity and progression of hip osteoarthritis. METHODS: From 2007 to 2009, we conducted a study of 242 patients aged between 40 and 75 years with symptomatic lower limb osteoarthritis, as part of a population-based osteoarthritis cohort study in France. Standard radiographs of both hips were obtained at baseline and at three years. The progression of hip osteoarthritis was evaluated according to the radiological Kellgren-Lawrence score (KL) and clinical severity from the scores on a Visual Analogic Scale (VAS) for pain recorded yearly. Five measures were used to describe hip morphology: centre edge angle, acetabular index (AI), vertical centre anterior angle, acetabular depth and neck-shaft angle. RESULTS: Of the 484 hips studied, 205 (42%) showed osteoarthritis at baseline and 16 (11 right and 5 left) underwent joint replacement during the follow-up. AI was the morphological measure most consistently and strongly associated with radiographic osteoarthritis at baseline (odds-ratio=1.05, 95% CI: 1.01-1.08 per degree of angle change), clinical severity (correlation coefficient with VAS during 3 years=0.15, P=0.004), radiological progression (odds-ratio=1.05, 95% CI: 1.00-1.10 per degree) and joint replacement (hazard ratio=1.18, 95% CI: 1.07-1.29 per degree). CONCLUSIONS: Acetabular obliquity and especially AI is strongly, and likely causally, associated with the existence, severity and progression of hip osteoarthritis. PMID- 26832188 TI - Identification of upstream regulators for synovial expression signature genes in osteoarthritis. AB - OBJECTIVES: The detection of transcription factors (TFs) for OA signature genes provides better clues to the underlying regulatory mechanisms and therapeutic applications. METHODS: We searched GEO database for synovial expression profiling from different OA microarray studies to perform a systematic analysis. Functional annotation of DEGs was conducted, including gene ontology (GO) enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Based on motif databases and the results from integrated analysis of current gene expression data, a global transcriptional regulatory network was constructed, and the upstream TFs were identified for OA signature genes. RESULTS: Six GEO datasets were obtained. Totally, 805 genes across the studies were consistently differentially expressed in OA (469 up-regulated and 336 down regulated genes) with FDR<=0.01. Supporting an involvement of ECM in the development of OA, we showed that ECM-receptor interaction was the most significant pathway in our KEGG analysis (P=5.92E-12). Sixty-one differentially expressed TFs were identified with FDR<=0.05. The constructed OA-specific regulatory networks consisted of 648 TF-target interactions between 51 TFs and 429 DEGs in the context of OA. The top 10 TFs covering the most downstream DEGs were identified as crucial TFs involved in the development of OA, including ARID3A, NFIC, ZNF354C, NR4A2, BRCA1, EHF, FOXL1, FOXC1, EGR1, and HOXA5. CONCLUSION: This integrated analysis has identified the OA signature, providing clues to pathogenesis of OA at the molecular level, which may be also used as diagnostic markers for OA. Some crucial upstream regulators, such as NR4A2, EHF, and EGR1 may be considered as potential new therapeutic targets for OA. PMID- 26832189 TI - JAK1-STAT3 blockade by JAK inhibitor SHR0302 attenuates inflammatory responses of adjuvant-induced arthritis rats and decreases Th17 and total B cells. AB - OBJECTIVE: To investigate the effects of JAK inhibitor (SHR0302) on adjuvant induced arthritis (AA) rats and the partial mechanisms focused on T, B lymphocyte subsets through JAK1-STAT3 pathway, including Th17, Treg, total B cells and memory B cells. METHODS: Animals were divided randomly into normal control, AA, SHR0302 (0.3,1.0, 3.0mg/kg) and MTX. The effects of SHR0302 on AA rats by evaluating arthritis index, arthritis global assessment and paw swelling degree, histopathology of joint and spleen. We examined the proliferation of T, B and FLS. Th17, Treg, total B and memory B cell proportion was measured by flow cytometry. Cytokines TNF-alpha, IL-1beta, IL-10, IL-17 and antibody IgG1, IgG2a levels in serum were measured by Elisa. The expression of p-JAK1 and p-STAT3 was measured by western blot. RESULTS: SHR0302 suppressed the severity of AA rats by attenuating the arthritis index, arthritis global assessment and paw swelling degree, and alleviated histopathology of spleen and joint of AA rats. SHR0302 can inhibit the proliferation of T, B and FLS, and down-regulated cytokines TNF alpha, IL-1beta, IL-17 and antibody IgG1, IgG2a levels, and suppressed the proportion of Th17 and total B, and inhibited JAK1-STAT3 phosphorylation. There was no significant effect on Treg function and memory B cell proportion. CONCLUSION: SHR0302 may attenuate the severity of AA rats, partially through reducing Th17 function and total B cell proportion by inhibiting JAK1-STAT3 phosphorylation. PMID- 26832190 TI - The roles of interferons in osteoclasts and osteoclastogenesis. AB - Interferons (IFNs) play essential roles in regulating osteoclast differentiation and bone resorption. Over the last decade, we have seen tremendous developments in our understanding of the mechanisms by which interferons regulate osteoclastogenesis. Of the type I interferons, IFN-beta inhibits osteoclastogenesis via autoregulatory or exogenous regulatory mechanisms, while IFN-alpha was recently shown to participate in regulating osteoclast formation. And the only member of type II interferons, IFN-gamma, has biphasic effects on osteoclastogenesis. Type III interferons have also been shown to be involved in osteoclast bone resorption, although no direct regulatory mechanism has been demonstrated. In this review, we provide an update account of the current knowledge on these recently revealed novel roles of interferons in the regulation of a variety of signaling pathways in osteoclast differentiation and function. The potential clinical applications are also discussed. PMID- 26832191 TI - Free Speech and Pharmaceutical Regulation -- Fishy Business. PMID- 26832192 TI - shot regulates the microtubule reorganization required for localization of axis determining mRNAs during oogenesis. AB - The Drosophila mid-oogenesis stages are notable as the time when most maternal mRNAs become localized at discrete regions of the oocyte. Microtubule rearrangement occurs during this period and is critical for the localization of axis-determining maternal mRNAs. We have identified shot as a key player in establishing the cytoskeletal arrangement required for the spatial localization of axis-determining maternal mRNAs. We also found that the spatial distribution of the Shot protein is regulated by its mRNA localization. Our results suggest that the RNA localization mechanism is used not only for restricted accumulation of patterning molecules but also for the microtubule organization that leads to the initial development of oocyte polarity. PMID- 26832193 TI - Red blood cell PK deficiency: An update of PK-LR gene mutation database. AB - Pyruvate kinase (PK) deficiency is known as being the most common cause of chronic nonspherocytic hemolytic anemia (CNSHA). Clinical PK deficiency is transmitted as an autosomal recessive trait, that can segregate neither in homozygous or in a compound heterozygous modality, respectively. Two PK genes are present in mammals: the pyruvate kinase liver and red blood cells (PK-LR) and the pyruvate kinase muscle (PK-M), of which only the first encodes for the isoenzymes normally expressed in the red blood cells (R-type) and in the liver (L-type). Several reports have been published describing a large variety of genetic defects in PK-LR gene associated to CNSHA. Herein, we present a review of about 250 published mutations and six polymorphisms in PK-LR gene with the corresponding clinical and molecular data. We consulted the PubMed website for searching mutations and papers, along with two main databases: the Leiden Open Variation Database (LOVD, https://grenada.lumc.nl/LOVD2/mendelian_genes/home.php?select_db=PKLR) and Human Gene Mutation Database (HGMD, http://www.hgmd.cf.ac.uk/ac/gene.php?gene=PKLR) for selecting, reviewing and listing the annotated PK-LR gene mutations present in literature. This paper is aimed to provide useful information to clinicians and laboratory professionals regarding overall reported PK-LR gene mutations, also giving the opportunity to harmonize data regarding PK-deficient individuals. PMID- 26832195 TI - The puzzling Venusian polar atmospheric structure reproduced by a general circulation model. AB - Unlike the polar vortices observed in the Earth, Mars and Titan atmospheres, the observed Venus polar vortex is warmer than the midlatitudes at cloud-top levels (~65 km). This warm polar vortex is zonally surrounded by a cold latitude band located at ~60 degrees latitude, which is a unique feature called 'cold collar' in the Venus atmosphere. Although these structures have been observed in numerous previous observations, the formation mechanism is still unknown. Here we perform numerical simulations of the Venus atmospheric circulation using a general circulation model, and succeed in reproducing these puzzling features in close agreement with the observations. The cold collar and warm polar region are attributed to the residual mean meridional circulation enhanced by the thermal tide. The present results strongly suggest that the thermal tide is crucial for the structure of the Venus upper polar atmosphere at and above cloud levels. PMID- 26832194 TI - CHOP Chemotherapy Followed by Tositumomab and Iodine-131 Tositumomab for Previously Untreated Diffuse Large B-cell Lymphoma. AB - The efficacy and safety of tositumomab/iodine-131 tositumomab (TST/I-131 TST) were evaluated in diffuse large B-cell lymphoma patients who responded to first line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Fifteen patients (median age, 52 years) received dosimetric and therapeutic doses of TST/I-131 TST. The most common Grade 3/4 hematologic adverse events were decreased absolute neutrophil count (47%), white blood cell count (40%), platelet count (27%), and hemoglobin (20%). The complete response (CR) rate increased from 60% post-CHOP to 80% post TST / I-131 TST. With a median follow-up of 120.0 months (range, 14-130 months), median duration of response (95% confidence intervals) was 58.4 months (12.0-not reached [NR]) for patients with confirmed complete response and 58.4 months (20.9-NR) for all confirmed responders. Median progression-free survival and time to treatment failure were 63.0 months (16.1 NR). Median overall survival was not reached; 2 patients died on study. CHOP and TST/I-131 TST demonstrated clinical activity with acceptable toxicity. PMID- 26832197 TI - [Resistant hypertension and no organ damage: A new case of Munchausen syndrome]. PMID- 26832198 TI - [Erythropoietin, chronic renal failure and cancer]. PMID- 26832199 TI - [Left-sided facial shaving hemineglect due to parietal ischaemia]. PMID- 26832200 TI - [Hypoxaemia and petequial rash after a crush]. PMID- 26832201 TI - [Multiple lymphoprolipherative disorders in a patient]. PMID- 26832202 TI - [Systemic lupus erythematosus with anti-centromere antibodies: An infrequent finding without scleroderma related features]. PMID- 26832203 TI - High-throughput quantification of antibiotic resistance genes from an urban wastewater treatment plant. AB - Antibiotic resistance among bacteria is a growing problem worldwide, and wastewater treatment plants have been considered as one of the major contributors to the dissemination of antibiotic resistance to the environment. There is a lack of comprehensive quantitative molecular data on extensive numbers of antibiotic resistance genes (ARGs) in different seasons with a sampling strategy that would cover both incoming and outgoing water together with the excess sludge that is removed from the process. In order to fill that gap we present a highly parallel quantitative analysis of ARGs and horizontal gene transfer potential over four seasons at an urban wastewater treatment plant using a high-throughput qPCR array. All analysed transposases and two-thirds of primer sets targeting ARGs were detected in the wastewater. The relative abundance of most of the genes was highest in influent and lower in effluent water and sludge. The resistance profiles of the samples cluster by sample location with a shift from raw influent through the final effluents and dried sludge to the sediments. Wastewater discharge enriched only a few genes, namely Tn25 type transposase gene and clinical class 1 integrons, in the sediment near the discharge pipe, but those enriched genes may indicate a potential for horizontal gene transfer. PMID- 26832204 TI - Microbial diversity in European alpine permafrost and active layers. AB - Permafrost represents a largely understudied genetic resource. Thawing of permafrost with global warming will not only promote microbial carbon turnover with direct feedback on greenhouse gases, but also unlock an unknown microbial diversity. Pioneering metagenomic efforts have shed light on the permafrost microbiome in polar regions, but temperate mountain permafrost is largely understudied. We applied a unique experimental design coupled to high-throughput sequencing of ribosomal markers to characterize the microbiota at the long-term alpine permafrost study site 'Muot-da-Barba-Peider' in eastern Switzerland with an approximate radiocarbon age of 12 000 years. Compared to the active layers, the permafrost community was more diverse and enriched with members of the superphylum Patescibacteria (OD1, TM7, GN02 and OP11). These understudied phyla with no cultured representatives proposedly feature small streamlined genomes with reduced metabolic capabilities, adaptations to anaerobic fermentative metabolisms and potential ectosymbiotic lifestyles. The permafrost microbiota was also enriched with yeasts and lichenized fungi known to harbour various structural and functional adaptation mechanisms to survive under extreme sub-zero conditions. These data yield an unprecedented view on microbial life in temperate mountain permafrost, which is increasingly important for understanding the biological dynamics of permafrost in order to anticipate potential ecological trajectories in a warming world. PMID- 26832205 TI - Macroscale distribution of virioplankton and heterotrophic bacteria in the Bohai Sea. AB - In light of limited research into the relationship between the macroscale distribution and dynamic changes of microplankton in the shallow Bohai Sea, here we used flow cytometry to analyse samples collected from the Bohai Sea channel in winter and summer. Results showed that the average of both viral abundance (VA) and bacterial abundance (BA) were lower in winter (3.61 * 10(7) and 1.84 * 10(6) cells/mL, respectively) than in summer (7.47 * 10(7) and 5.05 * 10(6) cells/mL, respectively). At all 16 stations, VA was one order of magnitude greater than BA, with a positive relationship between one another. In the horizontal distribution, variations in VA and BA followed a similar trend, and both were obviously higher near-shore than offshore. In the vertical distribution, variations in both VA and BA did not show a clear relationship with water depth. VA and BA in summer were 2.1 and 2.7 times those in winter, respectively. Spearman correlation analysis showed that both VA and BA were correlated with the concentration of PO4-P in winter (positive) and NO3-N in summer (negative). Additionally, BA showed a negative correlation with salinity. It is clear that the macroscale distribution of these two kinds of microbes in the Bohai Sea is related to seasonal variation and nutrient availability. PMID- 26832206 TI - Bridging the divide: a model-data approach to Polar and Alpine microbiology. AB - Advances in microbial ecology in the cryosphere continue to be driven by empirical approaches including field sampling and laboratory-based analyses. Although mathematical models are commonly used to investigate the physical dynamics of Polar and Alpine regions, they are rarely applied in microbial studies. Yet integrating modelling approaches with ongoing observational and laboratory-based work is ideally suited to Polar and Alpine microbial ecosystems given their harsh environmental and biogeochemical characteristics, simple trophic structures, distinct seasonality, often difficult accessibility, geographical expansiveness and susceptibility to accelerated climate changes. In this opinion paper, we explain how mathematical modelling ideally complements field and laboratory-based analyses. We thus argue that mathematical modelling is a powerful tool for the investigation of these extreme environments and that fully integrated, interdisciplinary model-data approaches could help the Polar and Alpine microbiology community address some of the great research challenges of the 21st century (e.g. assessing global significance and response to climate change). However, a better integration of field and laboratory work with model design and calibration/validation, as well as a stronger focus on quantitative information is required to advance models that can be used to make predictions and upscale processes and fluxes beyond what can be captured by observations alone. PMID- 26832207 TI - Thoracic endovascular aortic repair: A single center's 15-year experience. AB - OBJECTIVE: Specific complications of thoracic endovascular aortic repair (TEVAR) exist and long-term data are lacking. The purpose of this study was to evaluate our long-term TEVAR results. METHODS: This is a single-center retrospective study of 223 patients undergoing TEVAR from 1998 to 2013. Indication was aneurysm (45%), traumatic (26%), dissection (23%), and septic (6%). RESULTS: Patients' mean age was 62.7 +/- 17.9 years, 84% of them had an American Society of Anesthesiologists score >=3, and 42% had an aortic rupture. TEVAR was performed in zone 0 (n = 17), 1 (n = 17), or 2 (n = 59) in 42% of patients. Technical success rate was 96.4%. Overall 30-day mortality was 11.7% (elective aneurysm, 11.6%; emergent aneurysm, 34.3%; acute type B dissection, 14.8%; chronic dissection, 4.2%; septic, 8.3%; and traumatic, 1.7%). Major adverse events included stroke in 4.5%, spinal cord ischemia in 1.8%, and retrograde aortic dissection in 2.7%. Mean follow-up was 43.4 +/- 38 months. Estimated aortic complications-free survivals at 12, 36, 60, and 120 months were (% +/- standard error) 73% +/- 3%, 64% +/- 4%, 62% +/- 4% and 57% +/- 5%, respectively. Multivariate analysis showed that patients treated for a chronic aortic dissection had a significant risk of late reintervention (P = .001) CONCLUSIONS: Because of its simplicity and low morbimortality rate, TEVAR has become the first line approach for thoracic aortic diseases. Mortality outcomes are related to aortic pathology, emergent status, and proximal landing zone. To improve long term results, rigorous patient selection and follow-up, development of referral centers, and technologic evolution of materials have to be reached. PMID- 26832209 TI - An arterial faceoff classic: The "T off" between the right internal thoracic and radial arteries. PMID- 26832208 TI - Antiplatelet versus oral anticoagulant therapy as antithrombotic prophylaxis after mitral valve repair. AB - OBJECTIVE: To verify the rate of thromboembolic and hemorrhagic complications during the first 6 months after mitral valve repair and to assess whether the type of antithrombotic therapy influenced clinical outcome. METHODS: Retrospective data were retrieved from 19 centers. Inclusion criteria were isolated mitral valve repair with ring implantation. Exclusion criteria were ongoing or past atrial fibrillation and any combined intraoperative surgical procedures. The study cohort consisted of 1882 patients (aged 58 +/- 15 years; 36% women), and included 1517 treated with an oral anticoagulant (VKA group) and 365 with antiplatelet drugs (APLT group). Primary efficacy outcome was the incidence of arterial thromboembolic events within 6 months and primary safety outcome was the incidence of major bleeding within 6 months. Propensity matching was performed to obtain 2 comparable cohorts (858 vs 286). RESULTS: No differences were detected for arterial embolic complications in matched cohort (1.6% VKA vs 2.1% APLT; P = .50). Conversely, patients in the APLT group showed lower incidence of major bleeding complications (3.9% vs 0.7%; P = .01). Six month mortality rate was significantly higher in the VKA group (2.7% vs 0.3%; P = .02). Multivariable analysis in the matched cohort found VKA as independent predictor of major bleeding complications and mortality at 6 months. CONCLUSIONS: Vitamin K antagonist therapy was not superior to antiplatelet therapy to prevent thromboembolic complications after mitral valve repair. Our data suggest that oral anticoagulation may carry a higher bleeding risk compared with antiplatelet therapy, although these results should be confirmed in an adequately powered randomized controlled trial. PMID- 26832210 TI - Warfarin or aspirin after mitral valve repair: Why work harder? PMID- 26832211 TI - Venovenous extracorporeal membrane oxygenation for patients with single-ventricle anatomy: A registry report. AB - OBJECTIVE: Support with extracorporeal membrane oxygenation for cardiopulmonary failure is done so with venoarterial cannulation in the majority of children with single-ventricle anatomy. However, there is a growing experience for patients with pure oxygenation/ventilation impairment supported with venovenous extracorporeal membrane oxygenation. We describe that experience. METHODS: Data were collected from the Extracorporeal Life Support Organization registry for patients with single-ventricle anatomy supported with venovenous extracorporeal membrane oxygenation from 1990 to 2012. Descriptive statistics and multivariate analyses for associations with mortality were conducted. RESULTS: A total of 89 patients with single-ventricle anatomy had venovenous extracorporeal membrane oxygenation performed at a median age of 66 days (8-221). Survival to discharge was 48%. Fifty-four patients (61%) had shunt physiology, 22 patients (25%) had cavopulmonary connections, and 13 patients (14%) had single-ventricle anatomy but with no previous cardiac surgery. Indication for extracorporeal membrane oxygenation was respiratory failure in 59 patients (63%) and cardiac failure in 30 patients (32%). Double-lumen cannulas were used in 62 patients (70%). Bivariate analysis demonstrated that the duration of intubation before extracorporeal membrane oxygenation, mean airway pressure before cannulation, partial pressure carbon dioxide before cannulation, peak inspiratory pressure before cannulation, pump flow at 24 hours, extracorporeal membrane oxygenation run duration, and presence of renal injury were associated with mortality. Multivariate logistic analysis demonstrated that the duration of intubation (adjusted odds ratio, 1.01; 95% confidence interval, 1.003-1.016; P = .003), partial pressure carbon dioxide (adjusted odds ratio, 1.04; 95% confidence interval, 1.01-1.068; P = .007), mean airway pressure (adjusted odds ratio, 1.16; 95% confidence interval, 1.0-1.342; P = .05), and renal injury (adjusted odds ratio, 6.6; 95% confidence interval, 1.879-23.2; P = .003) were associated with mortality. CONCLUSIONS: Patients with single-ventricle anatomy in respiratory failure may be treated successfully with venovenous extracorporeal membrane oxygenation, with survival comparable to those treated with venoarterial extracorporeal membrane oxygenation for cardiac failure. Future research on indications for venovenous extracorporeal membrane oxygenation may aid clinicians in deciding the optimal approach for this challenging cohort. PMID- 26832212 TI - Improving long-term survival by preventing early complications after lung transplantation: Can we prevent ripples by keeping pebbles out of the water? PMID- 26832213 TI - Assessing the Usability of Web-Based Alcohol Education for Older Adults: A Feasibility Study. AB - BACKGROUND: Older adults can experience unfavorable health effects from drinking at relatively low consumption levels because of age-related physiological changes and alcohol's potentially adverse interactions with declining health, increased medication-use and diminishing functional status. At the same time, alcohol use in older adults may be protective against heart disease, stroke, and other disorders associated with aging. We developed "A Toast to Health in Later Life! Wise Drinking as We Age," a web-based educational intervention to teach older adults to balance drinking risks and benefits. OBJECTIVE: To examine the intervention's feasibility in a sample of community-dwelling current drinkers >=55 years of age and examine its effects on their quantity and frequency of alcohol use, adherence to standard drinking guidelines, and alcohol-related risks. METHODS: Participants were recruited in person, by mail and by telephone between September and October 2014 from a community-based social services organization serving Los Angeles County. Once enrolled, participants were randomly assigned to the intervention or to a control group. The conceptual frameworks for the intervention were the Health Belief Model, models of adult learning, and the US Department of Health and Human Services guidelines for designing easy-to-use websites. The intervention's content focuses on the relationship between drinking and its effects on older adults' medical conditions, use of medications, and ability to perform daily activities. It also addresses quantity and frequency of alcohol use, drinking and driving and binge drinking. The control group did not receive any special intervention. Data on alcohol use and risks for both groups came from the online version of the Alcohol Related Problems Survey and were collected at baseline and four weeks later. Data on usability were collected online from the intervention group immediately after it completed its review of the website. RESULTS: The 49 intervention and 47 control participants did not differ at baseline in age, ethnicity, medication use, medical conditions, or alcohol use and both groups were mostly female, college-educated, and in good health. Of the intervention participants, 94% (46/49) had little or no difficulty using the website, with 67% (33/49) reporting that they will change the way they think about drinking because of their exposure to the education. At the 4-week follow-up, the intervention group reported drinking less (P=.02). No changes between groups were found in quantity and frequency, adherence to recommended guidelines, or risk status. CONCLUSIONS: Community-dwelling older adults are receptive to online alcohol education. To be most effective, the education should be included as a component of a larger effort consisting of screening and counseling preferably in a health care setting. PMID- 26832215 TI - Synthesis of minoxidil conjugates and their evaluation as HL-60 differentiation agents. AB - Activation of minoxidil (MNX) with N,N'-carbonyldiimidazole and coupling with natural polyamines (PAs) and commercially available aliphatic or aromatic amines provided a series of new conjugates which were evaluated for their ability to induce differentiation to HL-60 acute myeloid leukemia cancer cells, using a modified NBTZ reduction test. Although neither MNX nor 4,4'-methylenedianiline (MDA) or 2,7-diaminofluorene (DAF), alone or in combination, had any effect, the MNX-spermine (SPM) conjugate (11) and the conjugates 7 and 8 of MNX with MDA and DAF exhibited a differentiation-inducing effect at a concentration of 10 MUM without being toxic on proliferating human peripheral blood mononuclear cells. PMID- 26832214 TI - The Role of CD44 in Glucose Metabolism in Prostatic Small Cell Neuroendocrine Carcinoma. AB - While prostatic adenocarcinomas are relatively indolent, some patients with advanced adenocarcinomas recur with small cell neuroendocrine carcinoma which is highly aggressive and lethal. Because glycolysis is a feature of malignancy and the degree of glycolysis generally correlates with tumor aggressiveness, we wanted to compare the metabolic differences and the molecular mechanisms involved between the two tumor types. In this study, and based on previous characterization, LNCaP and PC-3 prostate cancer cell lines were selected as models of prostatic adenocarcinoma and small cell neuroendocrine carcinoma, respectively. In addition to measuring glucose consumption, lactate secretion, and reactive oxygen species (ROS) levels, we performed metabolic profiling in these two model systems. The role of CD44 was studied by RNAi and lentivirus mediated overexpression. Expression of key enzymes in glycolysis was studied using human tissue microarrays containing benign prostate, adenocarcinoma, and small cell neuroendocrine carcinoma. Results showed that glycolytic features of PC-3 cells were higher than that of LNCaP cells. PFKFB4 was overexpressed in human small cell carcinoma tissue versus adenocarcinoma tissue. CD44 regulated glucose metabolism, intracellular ROS, and cell proliferation in PC-3 cells. Inhibition of CD44 also sensitized PC-3 cells to carboplatin. In conclusion, this study suggests different pathways of glucose metabolism contribute to the disparate biologic behaviors of these two tumor types. IMPLICATIONS: CD44 is an important regulator of glucose metabolism in small cell neuroendocrine carcinoma and may be an important therapeutic target. PMID- 26832216 TI - Sulfonamide inhibition studies of the gamma-carbonic anhydrase from the Antarctic bacterium Colwellia psychrerythraea. AB - The Antarctic bacterium Colwellia psychrerythraea encodes for a gamma-class carbonic anhydrase (CA, EC 4.2.1.1), which was cloned, purified and characterized. The enzyme (CpsCAgamma) has a moderate catalytic activity for the physiologic reaction of CO2 hydration to bicarbonate and protons, with a k(cat) 6.0*10(5) s(-1) and a k(cat)/K(m) of 4.7*10(6) M(-1) s(-1). A series of sulfonamides and a sulfamate were investigated as inhibitors of the new enzyme. The best inhibitor was metanilamide (K(I) of 83.5 nM) followed by indisulam, valdecoxib, celecoxib, sulthiame and hydrochlorothiazide (K(I)s ranging between 343 and 491 nM). Acetazolamide, methazolamide as well as other aromatic/heterocyclic derivatives showed inhibition constants between 502 and 7660 nM. The present study may shed some more light regarding the role that gamma CAs play in the life cycle of psychrophilic bacteria as the Antarctic one investigated here, by allowing the identification of inhibitors which may be useful as pharmacologic tools. PMID- 26832217 TI - Synthesis and antibacterial activity of pyridinium-tailored aromatic amphiphiles. AB - In this Letter, the antibacterial activities of pyridinium-tailored aromatic amphiphiles were evaluated by turbidimeter tests in vitro. The bioassays revealed that most of the target compounds exhibit appreciable inhibition activities against the plant pathogenic bacteria Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri. The half-maximal effective concentrations (EC50) of 2-NP-10, 9-AP-10, and 9-AP-7 against these three bacteria were relatively high, which may be ascribed to the favourable hydrophobicity/hydrophilicity balance in these compounds. Our results suggest that pyridinium-tailored aromatic amphiphiles are promising bactericide candidates against plant bacterial diseases. PMID- 26832218 TI - Synthesis and SAR of calcitonin gene-related peptide (CGRP) antagonists containing substituted aryl-piperazines and piperidines. AB - Calcitonin gene-related peptide (CGRP) is a potent neuropeptide implicated in the pathophysiology of migraine. In the course of seeking CGRP antagonists with improved oral bioavailability, metabolic stability, and pharmacokinetic properties, lower molecular weight, structurally simpler piperidine and piperazine analogs of BMS-694153 were prepared. Several were found to have nM binding affinity in vitro. The synthesis and SAR of these substituted piperidine and piperazine CGRP antagonists are discussed. PMID- 26832219 TI - Dispirocyclopropyldehydrocostus lactone selectively inhibits acute myelogenous leukemia cells. AB - Acute myeloid leukemia (AML) is a refractory disease, and the majority of AML patients died from relapse and multidrug resistance. More and more studies demonstrate that AML stem cells play key role in multidrug resistance of AML. Here, we report a derivative of dehydrocostus lactone, that is, dispirocyclopropyldehydrocostus lactone (DDL), showed preferable cytotoxicity against a series of leukemia cell lines and AML stem cells from clinical samples of AML patient. Meanwhile, DDL demonstrated no significant toxicity to normal hematopoietic cells. Therefore, the prodrug of DDL, DMADDL, was evaluated for its in vivo anti-AML activity. The result revealed that DMADDL could inhibit the tumor growth in SCID mice tumorigenicity assay. Further study suggested that DDL induced apoptosis mainly through the up-regulation of apoptosis related protein Bax, followed by the cleavage of caspase-3, caspase-9, and PARP. PMID- 26832220 TI - Effects of a novel carbocyclic analog of pyrrolo[2,3-d]pyrimidine nucleoside on pleiotropic induction of cell death in prostate cancer cells with different androgen responsiveness. AB - Prostate cancer is the most frequently diagnosed cancer and is one of the leading causes of male cancer death in the world. Recently, in the course of our screening for a novel anticancer compound, we synthesized carbocyclic analogs of pyrrolo[2,3-d]pyrimidine nucleoside; compounds 5, and 6. In the current study, we report the effects of compound 5 on pleiotropic induction of cell death via up regulation of AR-associated p21(Cip1) protein in prostate cancer cells with different androgen responsiveness, such as LNCaP (androgen-dependent and sensitive), LNCaP(C4-2) (androgen-independent and -sensitive; androgen refractory), and DU145 (androgen-independent and -insensitive) cells. The treatment of LNCaP cells with 6 MUM compound 5 for 24 h stimulated the androgen receptor (AR) activity and dramatically up-regulated transcription (56-fold) of p21(Cip1), which, in turn, induces typical apoptosis in the cells. However, induction of apoptosis through up-regulation (23-fold) of AR-associated p21(Cip1) achieved in LNCaP(C4-2) cells was possible by intensive cell treatment with compound 5 (9 MUM, 48 h), because the cells are less sensitive and independent to androgen than LNCaP cells. Furthermore, 6 MUM compound 5-treated DU145 cells, which exhibit extremely low AR activation due to no androgen responsiveness and dependency, showed neither up-regulation of p21(Cip1) nor apoptotic induction. Instead, a different type of cell death, autophagy-like death through the LC3B associated autophagosome formation, was obviously induced in DU145 cells. Taken together, our results suggest that pleiotropic induction of prostate cancer cell death by compound 5 is determined by how efficiently and how abundantly androgen dependent activation of the AR occurs, whereas compound 6 shows no induction of apoptosis in LNCaP cells. PMID- 26832221 TI - Novel hydrazone derivatives containing pyridine amide moiety: Design, synthesis, and insecticidal activity. AB - A series of novel hydrazone derivatives containing pyridine amide moiety were designed, synthesized, and evaluated for their insecticidal activity. Bioassays indicated that some of the target compounds exhibited good insecticidal activities against Nilaparvata lugens (N. lugens), Plutella xylostella (P. xylostella), Mythimna separata (M. separata), Helicoverpa armigera (H. armigera), Pyrausta nubilalis (P. nubilalis), and Culex pipiens pallens (C. pipiens pallens). In particular, compound 5j revealed excellent insecticidal activity against C. pipiens pallens, with the 50% lethal concentration (LC50) and the 95% lethal concentration (LC95) values of 2.44 and 5.76 mg/L, respectively, which were similar to those of chlorpyrifos (3.26 and 6.98 mg/L, respectively), tebufenozide (1.22 and 2.49 mg/L, respectively), and RH-5849 (2.61 and 6.37 mg/L, respectively). These results indicated that hydrazone derivatives containing pyridine amide moiety could be developed as novel and promising insecticides. PMID- 26832222 TI - Polycyclic amines as chloroquine resistance modulating agents in Plasmodium falciparum. AB - Pentacycloundecylamines (PCUs) and adamantane amines, such as NGP1-01 (1) and amantadine, have shown significant channel blocking activities. They are postulated to act as chemosensitizers and circumvent the resistance of the plasmodia parasite against chloroquine (CQ) by inhibiting the p-glycoprotein efflux pump and enabling the accumulation of CQ inside the parasite digestive vacuole. Twelve polycyclic amines containing either a PCU or adamantane amine moiety conjugated to different aromatic functionalities through various tethered linkers were selected based on their channel blocking abilities and evaluated as potential chemosensitizers. Compounds 2, 4, 5 and 10 showed significant voltage gated calcium channel (VGCC) blocking ability (IC50=0.27-35 MUM) and were able to alter the CQ IC50 in differing degrees (45-81%) in the multidrug resistant Plasmodium falciparum Dd2 isolate. Among them, the PCU-dansyl amine compound (4) displayed the best potential to act as a chemosensitizer against the Dd2 strain at a 1 MUM concentration (RMI=0.19) while displaying moderate antiplasmodial activity (Dd2 IC50=6.25 MUM) and low in vitro cytotoxicity against a mammalian cell line (CHO, IC50=119 MUM). Compounds 2 and 10 also showed some promising chemosensitizing abilities (RMI=0.36 and 0.35 respectively). A direct correlation was found between the VGCC blocking ability of these polycyclic amines and their capacity to act as CQ resistance modulating agents. PMID- 26832223 TI - Tailoring the physical properties of Ni-based single-phase equiatomic alloys by modifying the chemical complexity. AB - Equiatomic alloys (e.g. high entropy alloys) have recently attracted considerable interest due to their exceptional properties, which might be closely related to their extreme disorder induced by the chemical complexity. In order to understand the effects of chemical complexity on their fundamental physical properties, a family of (eight) Ni-based, face-center-cubic (FCC), equiatomic alloys, extending from elemental Ni to quinary high entropy alloys, has been synthesized, and their electrical, thermal, and magnetic properties are systematically investigated in the range of 4-300 K by combining experiments with ab initio Korring-Kohn Rostoker coherent-potential-approximation (KKR-CPA) calculations. The scattering of electrons is significantly increased due to the chemical (especially magnetic) disorder. It has weak correlation with the number of elements but strongly depends on the type of elements. Thermal conductivities of the alloys are largely lower than pure metals, primarily because the high electrical resistivity suppresses the electronic thermal conductivity. The temperature dependence of the electrical and thermal transport properties is further discussed, and the magnetization of five alloys containing three or more elements is measured in magnetic fields up to 4 T. PMID- 26832225 TI - Diagnosis and management of intracranial dural arteriovenous fistulas. AB - Dural arteriovenous fistula (DAVF) is a rare type of acquired intracranial vascular malformation. Recent progress in neuroimaging technology, such as advanced MRI and CT, provides non-invasive methods to accurately diagnose DAVF, including evaluation of the hemodynamics of the drainage veins. The clinical manifestations of DAVFs vary widely and depend on the location and venous drainage pattern of arteriovenous shunting. Patients with high grade DAVFs having cortical venous reflux should receive aggressive treatment to prevent the occurrence of intracranial hemorrhage and other neurological deficits related to venous congestion. Intra-arterial or intravenous endovascular embolization remains the primary therapy for high grade DAVF, while open surgery and stereotactic radiosurgery can serve as alternative treatment options. Early and accurate diagnosis with appropriate treatment is the goal for clinical management of DAVFs to reduce symptoms and prevent the development of venous congestion and stroke. PMID- 26832226 TI - 'The lesser of two evils...' - views of persons with rheumatoid arthritis on medication adherence: a qualitative study. AB - OBJECTIVE: This study aimed to explore medication adherence among adherent and non-adherent persons suffering from rheumatoid arthritis (RA). A special focus was put on the reasons accounting for successful medication adherence and on potential barriers or facilitating factors. DESIGN: A qualitative study with semi structured interviews was conducted. Eighteen participants were recruited through stratified purposive sampling according to their medication adherence level. Interviews were analysed by interpretative phenomenological analysis. RESULTS: Medication adherence behaviour was described on a continuum ranging from non adherent to adherent. Participants' current adherence level was represented as a result of inner negotiations between a variety of influential factors and the successful application of a range of strategies. The influential factors were: experiences with medication, outcome expectations, knowledge of therapeutic options, the traits 'openness' and 'conscientiousness', belief in medical progress, characteristics of the medication, level of trust in one's physician, and perceived autonomy. Facilitating strategies were: establishing routines, using social support and the deliberate suppression of information about potential adverse events. CONCLUSION: The experience of and the reasons for medication (non-)adherence from the perspective of people with RA were explored comprehensively. Participants' ongoing negotiations between adherence and non adherence emerged as a key finding with implications for health service providers. PMID- 26832224 TI - Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions. AB - Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is lacking. To address this, we used multiple small interfering RNAs (siRNAs) to silence GNG12-AS1, a nuclear lncRNA transcribed in an antisense orientation to the tumour-suppressor DIRAS3. Here we show that while most siRNAs silence GNG12-AS1 post-transcriptionally, siRNA complementary to exon 1 of GNG12 AS1 suppresses its transcription by recruiting Argonaute 2 and inhibiting RNA polymerase II binding. Transcriptional, but not post-transcriptional, silencing of GNG12-AS1 causes concomitant upregulation of DIRAS3, indicating a function in transcriptional interference. This change in DIRAS3 expression is sufficient to impair cell cycle progression. In addition, the reduction in GNG12-AS1 transcripts alters MET signalling and cell migration, but these are independent of DIRAS3. Thus, differential siRNA targeting of a lncRNA allows dissection of the functions related to the process and products of its transcription. PMID- 26832227 TI - Long-term results of minimally invasive stand-alone bi-atrial surgical ablation with a bipolar ablation device for persistent and longstanding persistent AF: a single-center case series of 91 patients. AB - BACKGROUND: Minimally invasive surgical treatment of lone atrial fibrillation (AF) is an alternative for AF that is refractory to medical treatment. We present long-term results of standalone surgical ablation of AF using a bipolar ablation device in 91 consecutive patients. METHODS: This was an observational, retrospective study of 91 patients (77 % males; mean age, 53 +/- 10 years [range, 23-75 years]) who underwent minimally invasive standalone surgical ablation of persistent and longstanding persistent AF using a bipolar ablation device from 2008 to 2014. Mean follow-up was 60 +/- 21 months. The absence of arrhythmia was confirmed at 3, 6, and 12 months, and annually thereafter, with 24-hour Holter monitoring. RESULTS: The mean duration of preoperative AF was 6.5 +/- 5.4 years. Persistent AF was present in 86 % of patients and longstanding persistent AF in 14 %. Mean left atrial diameter was 4.3 +/- 0.8 cm. There were two postoperative strokes (2 %) and three conversions to median sternotomy (3 %). Permanent pacemakers were implanted in six (7 %) patients. There were no intra- or postoperative deaths. At 1, 2, 3, 4, and 5 years postoperatively, freedom from AF was 59, 45, 41, 38, and 38 % of patients, respectively. The failure to achieve pulmonary vein isolation was the only independent predictor of long-term recurrence of AF (HR -3 [95 % CI 1,858 to 8,586], p = 0,001). There was a tendency towards higher rates of SR at long term follow up in patients with pulmonary vein isolation if division of ligament of Marshall was performed (HR - 2 [95 % CI 0.987 to 4,202], p = 0,067). CONCLUSIONS: In the present series, the efficacy of epicardial surgical ablation was similar to that reported previously. The rate of arrhythmia recurrence increased over time. Achieving pulmonary vein isolation is essential to AF elimination. The division of ligament of Marshall could contribute to improved rates of SR restoration in patients with persistent or long-standing persistent AF if PVI is achieved. PMID- 26832229 TI - Surface Engineering of Copper Foils for Growing Centimeter-Sized Single Crystalline Graphene. AB - The controlled growth of high-quality graphene on a large scale is of central importance for applications in electronics and optoelectronics. To minimize the adverse impacts of grain boundaries in large-area polycrystalline graphene, the synthesis of large single crystals of monolayer graphene is one of the key challenges for graphene production. Here, we develop a facile surface-engineering method to grow large single-crystalline monolayer graphene by the passivation of the active sites and the control of graphene nucleation on copper surface using the melamine pretreatment. Centimeter-sized hexagonal single-crystal graphene domains were successfully grown, which exhibit ultrahigh carrier mobilities exceeding 25,000 cm(2) V(-1) s(-1) and quantum Hall effects on SiO2 substrates. The underlying mechanism of melamine pretreatments were systematically investigated through elemental analyses of copper surface in the growth process of large single-crystals. This present work provides a surface design of a catalytic substrate for the controlled growth of large-area graphene single crystals. PMID- 26832228 TI - Corneal Power, Anterior Segment Length and Lens Power in 14-year-old Chinese Children: the Anyang Childhood Eye Study. AB - To analyze the components of young Chinese eyes with special attention to differences in corneal power, anterior segment length and lens power. Cycloplegic refractions and ocular biometry with LENSTAR were used to calculate lens power with Bennett's method. Mean refraction and mean values for the ocular components of five different refractive groups were studied with ANOVA and post-hoc Scheffe tests. There were 1889 subjects included with full data of refraction and ocular components. As expected, mean axial length was significantly longer in myopic eyes compared to emmetropes. Girls had steeper corneas, more powerful lenses and shorter eyes than boys. Lens power was lower in boys and also lower in myopic eyes. Lens thickness was the same for both genders but was lower in myopic eyes. Although cornea was steeper in myopic eyes in the whole sample, this was a gender effect (more girls in the myopic group) as this difference disappeared when the analysis was split by gender. Anterior segment length was longer in myopic eyes. In conclusion, myopic eyes have lower lens power and longer anterior segment length, that partially compensate their longer axial length. When analyzed by gender, the corneal power is not greater in low and moderate myopic eyes. PMID- 26832230 TI - Male hatchling production in sea turtles from one of the world's largest marine protected areas, the Chagos Archipelago. AB - Sand temperatures at nest depths and implications for hatchling sex ratios of hawksbill turtles (Eretmochelys imbricata) and green turtles (Chelonia mydas) nesting in the Chagos Archipelago, Indian Ocean are reported and compared to similar measurements at rookeries in the Atlantic and Caribbean. During 2012 2014, temperature loggers were buried at depths and in beach zones representative of turtle nesting sites. Data collected for 12,546 days revealed seasonal and spatial patterns of sand temperature. Depth effects were minimal, perhaps modulated by shade from vegetation. Coolest and warmest temperatures were recorded in the sites heavily shaded in vegetation during the austral winter and in sites partially shaded in vegetation during summer respectively. Overall, sand temperatures were relatively cool during the nesting seasons of both species which would likely produce fairly balanced hatchling sex ratios of 53% and 63% male hatchlings, respectively, for hawksbill and green turtles. This result contrasts with the predominantly high female skew reported for offspring at most rookeries around the globe and highlights how local beach characteristics can drive incubation temperatures. Our evidence suggests that sites characterized by heavy shade associated with intact natural vegetation are likely to provide conditions suitable for male hatchling production in a warming world. PMID- 26832231 TI - Unstable solar lentigo: A defined separate entity. AB - An unstable solar lentigo is a solar lentigo with areas of melanocytic hyperplasia not extending past the margin of the lesion. They are discrete, macular, pigmented lesions arising on sun-damaged skin and a subset of typical solar lentigos. Clinically they differ from usual solar lentigines in often being solitary or larger and darker than adjacent solar lentigines. These lesions are of clinical importance as they can arise in close proximity to lentigo maligna and in a single lesion there can be demonstrated changes of solar lentigo, unstable solar lentigo and lentigo maligna. These observations led us to conjecture that unstable solar lentigos could be a precursor lesion to lentigo maligna. In this article we examine the possibility that lentigo maligna can arise within a solar lentigo through an intermediate lesion, the unstable solar lentigo. We propose that the histopathological recognition of this entity will allow for future research into its behaviour and thus management. We review difficulties in the diagnosis of single cell predominant melanocytic proliferations and the concept of unstable lentigo in view of the literature and clinical experience supporting the proposal of its recognition as a separate entity. PMID- 26832232 TI - Analysis of the optimal temperature for the cryogenic monolithic Nd:YAG laser at 946-nm. AB - The optimal temperature for the cryogenic monolithic Nd:YAG laser at 946-nm is theoretically and experimentally analyzed. It is clear that decreasing temperature can considerably eliminate the thermal population at the lower laser level to enhance the quantum efficiency. However, the narrowing of the absorption bandwidth for the gain medium leads to a reduction of the effective absorption efficiency as the temperature is decreased. Consequently, an optimal temperature for the maximum output power is found to be in the range of approximately 120 K to 140 K. It is experimentally verified that employing a pump source with a narrower emission spectrum linewidth contributes a more efficient output for the cryogenic laser. PMID- 26832233 TI - Dual-view integral imaging 3D display by using orthogonal polarizer array and polarization switcher. AB - In this paper, a dual-view integral imaging three-dimensional (3D) display consisting of a display panel, two orthogonal polarizer arrays, a polarization switcher, and a micro-lens array is proposed. Two elemental image arrays for two different 3D images are presented by the display panel alternately, and the polarization switcher controls the polarization direction of the light rays synchronously. The two elemental image arrays are modulated by their corresponding and neighboring micro-lenses of the micro-lens array, and reconstruct two different 3D images in viewing zones 1 and 2, respectively. A prototype of the dual-view II 3D display is developed, and it has good performances. PMID- 26832234 TI - Coded excitation using periodic and unipolar M-sequences for photoacoustic imaging and flow measurement. AB - Photoacoustic imaging is an emerging imaging technology combining optical imaging with ultrasound. Imaging of the optical absorption coefficient and flow measurement provides additional functional information compared to ultrasound. The issue with photoacoustic imaging is its low signal-to-noise ratio (SNR) due to scattering or attenuation; this is especially problematic when high pulse repetition frequency (PRF) lasers are used. In previous research, coded excitation utilizing several pseudorandom sequences has been considered as a solution for the problem. However, previously proposed temporal coding procedures using Golay codes or M-sequences are so complex that it was necessary to send a sequence twice to realize a bipolar sequence. Here, we propose a periodic and unipolar sequence (PUM), which is a periodic sequence derived from an m-sequence. The PUM can enhance signals without causing coding artifacts for single wavelength excitation. In addition, it is possible to increase the temporal resolution since the decoding start point can be set to any code in periodic irradiation, while only the first code of a sequence was available for conventional aperiodic irradiation. The SNR improvement and the increase in temporal resolution were experimentally validated through imaging evaluation and flow measurement. PMID- 26832235 TI - Direct infrared femtosecond laser inscription of chirped fiber Bragg gratings. AB - We compare and contrast novel techniques for the fabrication of chirped broadband fiber Bragg gratings by ultrafast laser inscription. These methods enable the inscription of gratings with flexible period profiles and thus tailored reflection and dispersion characteristics in non-photosensitive optical fibers. Up to 19.5 cm long chirped gratings with a spectral bandwidth of up to 30 nm were fabricated and the grating dispersion was characterized. A maximum group delay of almost 2 ns was obtained for linearly chirped gratings with either normal or anomalous group velocity dispersion, demonstrating the potential for using these gratings for dispersion compensation. Coupling to cladding modes was reduced by careful design of the inscribed modification features. PMID- 26832236 TI - Interaction-induced mode switching in steady-state microlasers. AB - We demonstrate that due to strong modal interactions through cross-gain saturation, the onset of a new lasing mode can switch off an existing mode via a negative power slope. In this process of interaction-induced mode switching (IMS) the two involved modes maintain their identities, i.e. they do not change their spatial field patterns or lasing frequencies. For a fixed pump profile, a simple analytic criterion for the occurrence of IMS is given in terms of their self- and cross-interaction coefficients and non-interacting thresholds, which is verified for the example of a two-dimensional microdisk laser. When the spatial pump profile is varied as the pump power is increased, IMS can be induced even when it would not occur with a fixed pump profile, as we show for two coupled laser cavities. Our findings apply to steady-state lasing and are hence different from dynamical mode switching or hopping. IMS may have potential applications in robust and flexible all-optical switching. PMID- 26832237 TI - Structure modulated electrostatic deformable mirror for focus and geometry control. AB - We suggest a way to electrostatically control deformed geometry of an electrostatic deformable mirror (EDM) based on geometric modulation of a basement. The EDM is composed of a metal coated elastomeric membrane (active mirror) and a polymeric basement with electrode (ground). When an electrical voltage is applied across the components, the active mirror deforms toward the stationary basement responding to electrostatic attraction force in an air gap. Since the differentiated gap distance can induce change in electrostatic force distribution between the active mirror and the basement, the EDMs are capable of controlling deformed geometry of the active mirror with different basement structures (concave, flat, and protrusive). The modulation of the deformed geometry leads to significant change in the range of the focal length of the EDMs. Even under dynamic operations, the EDM shows fairly consistent and large deformation enough to change focal length in a wide frequency range (1~175 Hz). The geometric modulation of the active mirror with dynamic focus tunability can allow the EDM to be an active mirror lens for optical zoom devices as well as an optical component controlling field of view. PMID- 26832238 TI - Improving the detection limit of conformational analysis by utilizing a dual polarization Vernier cascade. AB - The dual polarization microring technique enables the simultaneous and accurate detection of thickness and refractive index of a bound molecular layer. By using three microring resonators in a double Vernier cascade configuration, the dual polarization technique is improved on three distinct levels: an increase of the sensitivity, a suppression of common noise due to self-referencing and the ability to migrate from a standard tunable laser to a cheap broadband LED and an on-chip arrayed waveguide grating as read-out system, allowing for a system which is orders of magnitude faster and cheaper. A dual polarization Vernier cascade proof-of-concept is fabricated and characterized, a read-out computational framework is constructed and it is shown on a theoretical basis that the limit of detection is improved. PMID- 26832239 TI - Exploiting broad-area surface emitting lasers to manifest the path-length distributions of finite-potential quantum billiards. AB - Broad-area vertical-cavity surface-emitting lasers (VCSELs) with different cavity sizes are experimentally exploited to manifest the influence of the finite confinement strength on the path-length distribution of quantum billiards. The subthreshold emission spectra of VCSELs are measured to obtain the path-length distributions by using the Fourier transform. It is verified that the number of the resonant peaks in the path-length distribution decreases with decreasing the confinement strength. Theoretical analyses for finite-potential quantum billiards are numerically performed to confirm that the mesoscopic phenomena of quantum billiards with finite confinement strength can be analogously revealed by using broad-area VCSELs. PMID- 26832240 TI - Optimization of a nanotip on a surface for the ultrafast probing of propagating surface plasmons. AB - We theoretically analyze a method for characterizing propagating surface plasmon polaritons (SPPs) on a thin gold film. The SPPs are excited by few-cycle near infrared pulses using Kretschmann coupling, and a nanotip is used as a local field sensor. This geometry removes the influence of the incident excitation laser from the near fields, and enhances the plasmon electric field strength. Using finite-difference-time-domain studies we show that the geometry can be used to measure SPP waveforms as a function of propagation distance. The effects of the nanotip shape and material on the field enhancement and plasmonic response are discussed. PMID- 26832241 TI - Enhanced pump absorption efficiency in coiled and twisted double-clad thulium doped fibers. AB - Results of the first experimental demonstration of the recently proposed technique for improvement of the pump absorption in double-clad fibers by their simultaneous coiling and twisting are reported. The peak absorption (14 dB) of 3 m long hexagonal thulium-doped fiber was increased by 8 dB by its simultaneous coiling and twisting. Explanation of the effect is given by numerical modelling of the pump absorption in hexagonal and panda-type double-clad fibers. Improvement of fiber laser performance was also proved. The slope efficiency increased from 19.6% of the straight fiber to 23.9% of the coiled only fiber and 29.4% of the simultaneously coiled and twisted fiber. PMID- 26832242 TI - High power Nd:YAG spinning disk laser. AB - We report on a high power Nd:YAG spinning disk laser. The eight cm diameter disk generated 200 W CW output with 323 W of absorbed pump in a near diffraction limited beam. The power conversion efficiency was 64%. The pulsed result, 5 ms pulses at 10 Hz PRF, was nearly identical to the CW result indicating good thermal management. Rotated at 1200-1800 RPM with He impingement cooling the disk temperature increased by only 17 degrees C reaching a maximum temperature of ~31 degrees C. The thermal dissipation per unit of output power was 0.61 watt of heat generated per watt of laser output, which is below the typical range of 0.8 1.1 for 808 nm diode pumped Nd:YAG lasers. PMID- 26832243 TI - Observation of an optical event horizon in a silicon-on-insulator photonic wire waveguide. AB - We report on the first experimental observation of an optical analogue of an event horizon in integrated nanophotonic waveguides, through the reflection of a continuous wave on an intense pulse. The experiment is performed in a dispersion engineered silicon-on-insulator waveguide. In this medium, solitons do not suffer from Raman induced self-frequency shift as in silica fibers, a feature that is interesting for potential applications of optical event horizons. As shown by simulations, this also allows the observation of multiple reflections at the same time on fundamental solitons ejected by soliton fission. PMID- 26832244 TI - Heralded amplification of photonic qubits. AB - We demonstrate postselection free heralded qubit amplification for Time-Bin qubits and single photon states in an all-fibre, telecom-wavelength, scheme that highlights the simplicity, stability and potential for fully integrated photonic solutions. Exploiting high-efficiency superconducting detectors, the gain, fidelity and the performance of the amplifier are studied as a function of loss. We also demonstrate the first heralded single photon amplifier with independent sources. This provides a significant advance towards demonstrating device independent quantum key distribution as well as fundamental tests of quantum mechanics over extended distances. PMID- 26832245 TI - Graphene/h-BN/GaAs sandwich diode as solar cell and photodetector. AB - In graphene/semiconductor heterojunction, the statistic charge transfer between graphene and semiconductor leads to decreased junction barrier height and limits the Fermi level tuning effect in graphene, which greatly affects the final performance of the device. In this work, we have designed a sandwich diode for solar cells and photodetectors through inserting 2D hexagonal boron nitride (h BN) into graphene/GaAs heterostructure to suppress the static charge transfer. The barrier height of graphene/GaAs heterojunction can be increased from 0.88 eV to 1.02 eV by inserting h-BN. Based on the enhanced Fermi level tuning effect with interface h-BN, through adopting photo-induced doping into the device, power conversion efficiency (PCE) of 10.18% has been achieved for graphene/h-BN/GaAs compared with 8.63% of graphene/GaAs structure. The performance of graphene/h BN/GaAs based photodetector is also improved with on/off ratio increased by one magnitude compared with graphene/GaAs structure. PMID- 26832246 TI - Alignment sensing and control for squeezed vacuum states of light. AB - Beam alignment is an important practical aspect of the application of squeezed states of light. Misalignments in the detection of squeezed light result in a reduction of the observable squeezing level. In the case of squeezed vacuum fields that contain only very few photons, special measures must be taken in order to sense and control the alignment of the essentially dark beam. The GEO 600 gravitational wave detector employs a squeezed vacuum source to improve its detection sensitivity beyond the limits set by classical quantum shot noise. Here, we present our design and implementation of an alignment sensing and control scheme that ensures continuous optimal alignment of the squeezed vacuum field at GEO 600 on long time scales in the presence of free-swinging optics. This first demonstration of a squeezed light automatic alignment system will be of particular interest for future long-term applications of squeezed vacuum states of light. PMID- 26832247 TI - Influence of wavefront aberration on the imaging performance of the solar grating spectrometer. AB - The solar grating spectrometer is an important tool to study the thermodynamic properties of the solar atmosphere with different height distribution, but its imaging performance will be degraded by the wavefront aberration. On the other hand, narrow slit of the grating spectrometer will filter the wavefront aberration to a certain extent. In this paper, the mathematical relation between the wavefront aberration and the imaging performance of the grating spectrometer is derived. The numerical simulation is performed and is validated by the experiment. The results demonstrate that: The influence of the wavefront aberration with the different types and magnitudes on the spectral resolution and the energy utilization is different. The influence of the different slits on the wavefront aberrations is different. Generally, the smaller the slit is, the better the spectral resolution is. However, this is not true for the low frequency dominated aberration, e.g. the defocus, since its low frequency will also be blocked by the narrow slit. If the influence of the filter slit on the wavefront aberration cannot be taken into account, it will lead to adaptive optics over-compensation. PMID- 26832248 TI - 360-degrees profilometry using strip-light projection coupled to Fourier phase demodulation. AB - 360 degrees (360 degrees ) digitalization of three dimensional (3D) solids using a projected light-strip is a well-established technique in academic and commercial profilometers. These profilometers project a light-strip over the digitizing solid while the solid is rotated a full revolution or 360-degrees. Then, a computer program typically extracts the centroid of this light-strip, and by triangulation one obtains the shape of the solid. Here instead of using intensity-based light-strip centroid estimation, we propose to use Fourier phase demodulation for 360 degrees solid digitalization. The advantage of Fourier demodulation over strip-centroid estimation is that the accuracy of phase demodulation linearly-increases with the fringe density, while in strip-light the centroid-estimation errors are independent. Here we proposed first to construct a carrier-frequency fringe-pattern by closely adding the individual light-strip images recorded while the solid is being rotated. Next, this high-density fringe pattern is phase-demodulated using the standard Fourier technique. To test the feasibility of this Fourier demodulation approach, we have digitized two solids with increasing topographic complexity: a Rubik's cube and a plastic model of a human-skull. According to our results, phase demodulation based on the Fourier technique is less noisy than triangulation based on centroid light-strip estimation. Moreover, Fourier demodulation also provides the amplitude of the analytic signal which is a valuable information for the visualization of surface details. PMID- 26832249 TI - Diffraction grating-based sensing optofluidic device for measuring the refractive index of liquids. AB - We describe a simple and versatile optical sensing device for measuring refractive index of liquids. The sensor consists of a sinusoidal relief grating in a glass cell. Device calibration is done by pouring in the cell different liquids of known refractive indices. Each time a liquid is poured first order intensity is measured. The fabrication process and testing of the prototype device is described. An application in the measurement of temperature is also presented. PMID- 26832250 TI - High performace silicon 2x2 optical switch based on a thermo-optically tunable multimode interference coupler and efficient electrodes. AB - Optical switches based on tunable multimode interference (MMI) couplers can simultaneously reduce the footprint and increase the tolerance against fabrication deviations. Here, a compact 2x2 silicon switch based on a thermo optically tunable MMI structure with a footprint of only 0.005 mm(2) is proposed and demonstrated. The MMI structure has been optimized using a silica trench acting as a thermal isolator without introducing any substantial loss penalty or crosstalk degradation. Furthermore, the electrodes performance have significantly been improved via engineering the heater geometry and using two metallization steps. Thereby, a drastic power consumption reduction of around 90% has been demonstrated yielding to values as low as 24.9 mW. Furthermore, very fast switching times of only 1.19 us have also been achieved. PMID- 26832251 TI - Reaction ion etching process for improving laser damage resistance of fused silica optical surface. AB - Laser induced damage of fused silica optics occurs primarily on optical surface or subsurface resulting from various defects produced during polishing/grinding process. Many new kinds of surface treatment processes are explored to remove or control the defects on fused silica surface. In this study, we report a new application of reaction ion etching (RIE)-based surface treatment process for manufacture of high quality fused silica optics. The influence of RIE processes on laser damage resistance as a function of etching depth and the evolution of typical defects which are associated with laser damage performance were investigated. The results show that the impurity element defects and subsurface damage on the samples surface were efficiently removed and prevented. Pure silica surface with relatively single-stable stoichiometry and low carbon atomic concentration was created during the etching. The laser damage resistance of the etched samples increased dramatically. The increase of roughness and ODC point defect with deeper etching are believed to be the main factors to limit further increase of the damage resistance of fused silica. The study is expected to contribute to the development of fused silica optics with high resistance to laser induced degradation in the future. PMID- 26832252 TI - Generation and detection of broadband multi-channel orbital angular momentum by micrometer-scale meta-reflectarray. AB - We theoretically demonstrate the generation and detection of broadband multi channel Orbital Angular Momentum(OAM) by a micrometer-scale meta-reflectarray. The meta-reflectarray composed of patterned silicon bars on a silver ground plane can be designed to realize phase modulation and work as chip-level OAM devices. Compared to traditional methods of OAM generation and detection, our approach shows superiorities of very compact structure size, broadband working wavelength (1250-1750 nm), high diffraction efficiency (~70%), simultaneously handling multiplex OAMs, and tunable reflection angle (0-45 degrees ). These fascinating advantages provides great potential applications in photonic integrated devices and systems for high-capacity and multi-channel OAM communication. PMID- 26832253 TI - Outage capacity of FSO link with pointing errors and link blockage. AB - In this paper, we analyze the outage capacity performance of free-space optical (FSO) systems. More precisely, taking the stochastic temporary blockage of the laser beam, atmospheric turbulence, misalignment between transmitter laser and receiver photodiode and path loss into account, we derive novel accurate analytical expressions for the outage capacity. The intensity fluctuations of the received signal are modeled by a Gamma-Gamma distribution with parameters directly related to the wide range of atmospheric conditions. The analytical results are validated by Monte Carlo simulations. Furthermore, when the intensity fluctuations are caused only by atmospheric turbulence, derived expressions are reduced to the simpler forms already presented in literature. The numerical and simulation results show that the link blockage causes appearance of the outage floor that is a significant energetic characteristic of an FSO system. The results also show that there exists an optimal value of the laser beam radius at the waist for minimizing outage probability in order to achieve the specified outage capacity. This optimal value depends on atmospheric turbulence strength and standard deviation of pointing errors, but it is also strongly dependent on the probability of link blockage. PMID- 26832254 TI - Guided-mode resonance assisted directional emission of a wavelength-shifting film for application in scintillation detection. AB - Thin-film luminescent layers as wavelength shifters using in the scintillation detection system suffer with low efficiency due to the total internal reflection and the non-directional emission. In the present work, we design and fabricate a photonic crystal on the surface of LuTaO(4):Eu(3+) thin-film which is a newly developed luminescent material using in radiation detection systems. The entire structure shows guided-mode resonances with only one TE and TM mode. As a result, the emitting light is effectively extracted. Furthermore, due to only two modes existing in the layer, the directionality of emission is strongly controlled. This result enables the structured LuTaO(4):Eu(3+) thin-film to be a potential wavelength shifter with high-efficiency. PMID- 26832255 TI - Optimal all-optical switching of a microcavity resonance in the telecom range using the electronic Kerr effect. AB - We have switched GaAs/AlAs and AlGaAs/AlAs planar microcavities that operate in the "Original" (O) telecom band by exploiting the instantaneous electronic Kerr effect. We observe that the resonance frequency reversibly shifts within one picosecond when the nanostructure is pumped with low-energy photons. We investigate experimentally and theoretically the role of several parameters: the material backbone and its electronic bandgap, the quality factor, and the duration of the switch pulse. The magnitude of the frequency shift is reduced when the backbone of the central lambda-layer has a greater electronic bandgap compared to the cavity resonance frequency and the frequency of the pump. This observation is caused by the fact that pumping with photon energies near the bandgap resonantly enhances the switched magnitude. We thus find that cavities operating in the telecom O-band are more amenable to ultrafast Kerr switching than those operating at lower frequencies, such as the C-band. Our results indicate that the large bandgap of AlGaAs/AlAs cavity allows to tune both the pump and the probe to the telecom range to perform Kerr switching without detrimental two-photon absorption. We observe that the magnitude of the resonance frequency shift decreases with increasing quality factor of the cavity. Our model shows that the magnitude of the resonance frequency shift depends on the pump pulse duration and is maximized when the duration matches the cavity storage time to within a factor two. In our experiments, we obtain a maximum shift of the cavity resonance relative to the cavity linewidth of 20%. We project that the shift of the cavity resonance can be increased twofold with a pump pulse duration that better matches the cavity storage time. We provide the essential parameter settings for different materials so that the frequency shift of the cavity resonance can be maximized using the electronic Kerr effect. PMID- 26832256 TI - Localized surface plasmon resonance in the IR regime. AB - Arrays of differently sized disk shaped gold nanoantennas are prepared on glass, which show localized surface plasmon resonance and Rayleigh anomalies in the near infrared and telecom range between 1000 and 1500 nm wavelength. The spectral position of these grating resonances depends critically on the period of the array and the size of the nanoantennas. When PbS quantum dots embedded in PMMA surround the nanoantennas, an up to four fold enhancement of the photoluminescence is observed at the grating resonances due to the constructive diffractive feedback among neighboring antennas. In accordance with the grating resonances a shift of the emission towards smaller wavelengths with decreasing disk diameter is demonstrated. PMID- 26832257 TI - M-line spectroscopy on mid-infrared Si photonic crystals for fluid sensing and chemical imaging. AB - The presented work demonstrates the design and characterization of Si-based photonic crystal waveguides operating as an evanescent wave absorption sensor in the mid-IR range lambda = 5-6 um. The photonic crystal structure is fabricated in a Si slab upon a thin Si(3)N(4)/TEOS/Si(3)N(4) membrane. M-line spectroscopy is used to verify the presence of guided waves. Different fillings of the photonic crystal holes have been realized to avoid sample residuals in the holes and, at the same time, to obtain spectral tuning of the structures by modification of the refractive index contrast with the photonic background. The chip displays sensitivity to fluid droplets in two-prism experiments. The output signal is quantitatively related to the fluid's absorption coefficient thereby validating the experimental method. PMID- 26832258 TI - Improvement of terahertz field effect transistor detectors by substrate thinning and radiation losses reduction. AB - Phenomena of the radiation coupling to the field effect transistors based terahertz (THz) detectors are studied. We show that in the case of planar metal antennas a significant portion of incoming radiation, instead of being coupled to the transistors, is coupled to an antenna substrate leading to responsivity losses and/or cross-talk effects in the field effect based THz detector arrays. Experimental and theoretical investigations of the responsivity versus substrate thickness are performed. They clearly show how to minimize the losses by the detector/ array substrate thinning. In conclusion simple quantitative rules of losses minimization by choosing a proper substrate thickness of field effect transistor THz detectors are presented for common materials (Si, GaAs, InP, GaN) used in semiconductor technologies. PMID- 26832259 TI - White-light generation control with crossing beams of femtosecond laser pulses. AB - We investigated the variations in generated white-light when crossing two femtosecond laser beams in a Kerr medium. By changing the relative delay of two interacting intense femtosecond laser pulses, we show that white-light generation can be enhanced or suppressed. With a decrease of the relative delay an enhancement of the white-light output was observed, which at even smaller delays was reverted to a suppression of white-light generation. Under choosen conditions, the level of suppression resulted in a white-light output lower than the initial level corresponding to large delays, when the pulses do not overlap in time. The enhancement of the white-light generation takes place in the pulse that is lagging. We found that the effect of the interaction of the beams depends on their relative orientation of polarization and increases when the polarizations are changed from perpendicular to parallel. The observed effects are explained by noting that at intermediate delays, the perturbations introduced in the path of the lagging beam lead to a shortening of the length of filament formation and enhancement of the white-light generation, whereas at small delays the stronger interaction and mutual rescattering reduces the intensity in the central part of the beams, suppressing filamentation and white-light generation. PMID- 26832260 TI - High-Q, ultrathin-walled microbubble resonator for aerostatic pressure sensing. AB - Sensors based on whispering gallery resonators have minute footprints and can push achievable sensitivities and resolutions to their limits. Here, we use a microbubble resonator, with a wall thickness of 500 nm and an intrinsic Q-factor of 10(7) in the telecommunications C-band, to investigate aerostatic pressure sensing via stress and strain of the material. The microbubble is made using two counter-propagating CO(2) laser beams focused onto a microcapillary. The measured sensitivity is 19 GHz/bar at 1.55 MUm. We show that this can be further improved to 38 GHz/bar when tested at the 780 nm wavelength range. In this case, the resolution for pressure sensing can reach 0.17 mbar with a Q-factor higher than 5 * 10(7). PMID- 26832261 TI - Vernier-like super resolution with guided correlated photon pairs. AB - We describe a dispersion-enabled, ultra-low power realization of super-resolution in an integrated Mach-Zehnder interferometer. Our scheme is based on a Vernier like effect in the coincident detection of frequency correlated, non-degenerate photon pairs at the sensor output in the presence of group index dispersion. We design and simulate a realistic integrated refractive index sensor in a silicon nitride on silica platform and characterize its performance in the proposed scheme. We present numerical results showing a sensitivity improvement upward of 40 times over a traditional sensing scheme. The device we design is well within the reach of modern semiconductor fabrication technology. We believe this is the first metrology scheme that uses waveguide group index dispersion as a resource to attain super-resolution. PMID- 26832262 TI - Cavity-enhanced absorption spectroscopy with a ps-pulsed UV laser for sensitive, high-speed measurements in a shock tube. AB - We report the first application of cavity-enhanced absorption spectroscopy (CEAS) with a ps-pulsed UV laser for sensitive and rapid gaseous species time-history measurements in a transient environment (in this study, a shock tube). The broadband nature of the ps pulses enabled instantaneous coupling of the laser beam into roughly a thousand cavity modes, which grants excellent immunity to laser-cavity coupling noise in environments with heavy vibrations, even with an on-axis alignment. In this proof-of-concept experiment, we demonstrated an absorption gain of 49, which improved the minimum detectable absorbance by ~20 compared to the conventional single-pass strategy at similar experimental conditions. For absorption measurements behind reflected shock waves, an effective time-resolution of ~2 MUs was achieved, which enabled time-resolved observations of transient phenomena, such as the vibrational relaxation of O(2) demonstrated here. The substantial improvement in detection sensitivity, together with microsecond measurement resolution implies excellent potential for studies of transient physical and chemical processes in nonequilibrium situations, particularly via measurements of weak absorptions of trace species in dilute reactive systems. PMID- 26832263 TI - Shear Brillouin light scattering microscope. AB - Brillouin spectroscopy has been used to characterize shear acoustic phonons in materials. However, conventional instruments had slow acquisition times over 10 min per 1 mW of input optical power, and they required two objective lenses to form a 90 degrees scattering geometry necessary for polarization coupling by shear phonons. Here, we demonstrate a confocal Brillouin microscope capable of detecting both shear and longitudinal phonons with improved speeds and with a single objective lens. Brillouin scattering spectra were measured from polycarbonate, fused quartz, and borosilicate in 1-10 s at an optical power level of 10 mW. The elastic constants, phonon mean free path and the ratio of the Pockels coefficients were determined at microscopic resolution. PMID- 26832264 TI - Interferometric Near-Infrared Spectroscopy (iNIRS) for determination of optical and dynamical properties of turbid media. AB - We introduce and implement interferometric near-infrared spectroscopy (iNIRS), which simultaneously extracts optical and dynamical properties of turbid media through analysis of a spectral interference fringe pattern. The spectral interference fringe pattern is measured using a Mach-Zehnder interferometer with a frequency-swept narrow linewidth laser. Fourier analysis of the detected signal is used to determine time-of-flight (TOF)-resolved intensity, which is then analyzed over time to yield TOF-resolved intensity autocorrelations. This approach enables quantification of optical properties, which is not possible in conventional, continuous-wave near-infrared spectroscopy (NIRS). Furthermore, iNIRS quantifies scatterer motion based on TOF-resolved autocorrelations, which is a feature inaccessible by well-established diffuse correlation spectroscopy (DCS) techniques. We prove this by determining TOF-resolved intensity and temporal autocorrelations for light transmitted through diffusive fluid phantoms with optical thicknesses of up to 55 reduced mean free paths (approximately 120 scattering events). The TOF-resolved intensity is used to determine optical properties with time-resolved diffusion theory, while the TOF-resolved intensity autocorrelations are used to determine dynamics with diffusing wave spectroscopy. iNIRS advances the capabilities of diffuse optical methods and is suitable for in vivo tissue characterization. Moreover, iNIRS combines NIRS and DCS capabilities into a single modality. PMID- 26832265 TI - Pushing x-ray photon correlation spectroscopy beyond the continuous frame rate limit. AB - We demonstrate delayed-frame X-ray Photon Correlation Spectroscopy with 120 microsecond time resolution, limited only by sample scattering rates, with a prototype Pixel-array detector capable of taking two image frames separated by 153 ns or less. Although the overall frame rate is currently limited to about 4 frame pairs per second, we easily measured millisecond correlation functions. This technology, coupled to the use of brighter synchrotrons such as Petra III or the NSLS-II should enable X-ray Photon Correlation Spectroscopy on microsecond time scales on a wider variety of materials. PMID- 26832266 TI - Multi-port admittance model for quantifying the scattering response of loaded plasmonic nanorod antennas: erratum. AB - This erratum corrects Fig. 5 in [Opt. Express 23(4), 4459-4471 (2015) 10.1364/OE.23.00445925836483]. PMID- 26832267 TI - Realistic optical cell modeling and diffraction imaging simulation for study of optical and morphological parameters of nucleus. AB - Coherent light scattering presents complex spatial patterns that depend on morphological and molecular features of biological cells. We present a numerical approach to establish realistic optical cell models for generating virtual cells and accurate simulation of diffraction images that are comparable to measured data of prostate cells. With a contourlet transform algorithm, it has been shown that the simulated images and extracted parameters can be used to distinguish virtual cells of different nuclear volumes and refractive indices against the orientation variation. These results demonstrate significance of the new approach for development of rapid cell assay methods through diffraction imaging. PMID- 26832268 TI - Direct core structuring of microstructured optical fibers using focused ion beam milling. AB - We demonstrate the use of focused ion beam milling to machine optical structures directly into the core of microstructured optical fibers. The particular fiber used was exposed-core microstructured optical fiber, which allowed direct access to the optically guiding core. Two different designs of Fabry-Perot cavity were fabricated and optically characterized. The first cavity was formed by completely removing a section of the fiber core, while the second cavity consisted of a shallow slot milled into the core, leaving the majority of the core intact. This work highlights the possibility of machining complex optical devices directly onto the core of microstructured optical fibers using focused ion beam milling for applications including environmental, chemical, and biological sensing. PMID- 26832269 TI - Phase-coherent orthogonally polarized optical single sideband modulation with arbitrarily tunable optical carrier-to-sideband ratio. AB - We propose and experimentally verify a novel approach to achieve phase-coherence orthogonally polarized optical single sideband (OSSB) modulation with a tunable optically carrier-to-sideband ratio (OCSR). In our scheme, the orthogonally polarized OSSB signal is achieved using a dual-polarization quadrature phase shift keying (DP-QPSK) modulator without an optical band-pass filter (OBPF). Therefore, the proposed method is wavelength independent. The DP-QPSK modulator includes two parallel QPSK modulators locating on its two arms. The upper QPSK modulator of the DP-QPSK modulator is driven by two quadrature sinusoidal microwave signals and works at the frequency shifting condition whose bias voltages are optimized to suppress the optical. The lower QPSK modulator of that works at the maximum transmission point and the optical carrier is not modulated. The OCSR is continuously tunable by simply adjusting the bias voltages of the lower modulator. The frequency shifting optical signal from the upper QPSK modulator and the optical carrier from the lower QPSK modulator are combined together at the output of the DP-QPSK modulator. The optical carrier and sideband are polarized orthogonally. The generated OSSB signals could be used to shift and code the phase of the microwave signal and generate ultra-wideband (UWB) microwave pulse. The proposed method is analyzed and experimental demonstrated. PMID- 26832270 TI - Single-pixel camera with one graphene photodetector. AB - Consumer cameras in the megapixel range are ubiquitous, but the improvement of them is hindered by the poor performance and high cost of traditional photodetectors. Graphene, a two-dimensional micro-/nano-material, recently has exhibited exceptional properties as a sensing element in a photodetector over traditional materials. However, it is difficult to fabricate a large-scale array of graphene photodetectors to replace the traditional photodetector array. To take full advantage of the unique characteristics of the graphene photodetector, in this study we integrated a graphene photodetector in a single-pixel camera based on compressive sensing. To begin with, we introduced a method called laser scribing for fabrication the graphene. It produces the graphene components in arbitrary patterns more quickly without photoresist contamination as do traditional methods. Next, we proposed a system for calibrating the optoelectrical properties of micro/nano photodetectors based on a digital micromirror device (DMD), which changes the light intensity by controlling the number of individual micromirrors positioned at + 12 degrees . The calibration sensitivity is driven by the sum of all micromirrors of the DMD and can be as high as 10(-5)A/W. Finally, the single-pixel camera integrated with one graphene photodetector was used to recover a static image to demonstrate the feasibility of the single-pixel imaging system with the graphene photodetector. A high resolution image can be recovered with the camera at a sampling rate much less than Nyquist rate. The study was the first demonstration for ever record of a macroscopic camera with a graphene photodetector. The camera has the potential for high-speed and high-resolution imaging at much less cost than traditional megapixel cameras. PMID- 26832271 TI - Measurement of phase retardation of optical multilayer films based on laser feedback system. AB - The phase property of optical films is becoming a new research focus in optoelectronics. The retardation caused by reflection on multilayer optical films can be utilized to make phase retarders and modulate the polarization state of optical systems. In this paper, a novel method based on laser feedback is presented to measure the retardance. The laser feedback system can realize fast and stable measurement with high accuracy. Two samples of K9 glass covered with different multilayer optical films are measured at different angles of incidence. The results show that the retardance is sensitive to the incident angle and can provide guidance for the usage of reflective optical films. PMID- 26832272 TI - Direct high-precision measurement of the effective optical path length of multi pass cell with optical frequency domain reflectometer. AB - Multi-pass cells (MPCs) are commonly used in trace-gas detection and weak spectrum measurement. It is essential to accomplish a high-precision measurement of MPCs' effective optical path length (EOPL). A direct high-precision measuring method of MPCs' EOPL with optical frequency domain reflectometer (OFDR) was reported and demonstrated in this paper. Several important parameters of a MPC, such as EOPL and base length, were derived with high-precision by identifying the complicated signal of OFDR. The MPC's EOPL was also verified with the prevailing absorbance method. The results showed that the MPC's EOPL measured by each of these two methods is highly consistent. However, the relative uncertainty with the OFDR dramatically decreased 2 orders of magnitude (about 0.0085%) than that with the absorbance method. It demonstrated that the OFDR method with fewer measurement links is more conducive to a direct measurement. The performances of beam spread and stray light in the White-cell were also evaluated with the method. PMID- 26832273 TI - Excitation of crest and trough surface plasmon modes in in-plane bended graphene nanoribbons. AB - To achieve efficiently coupling to external light is still remaining an insurmountable challenge that graphene faces before it can play an irreplaceable role in the plasmonic field. Here, this difficulty is overcome by a scheme capable of exciting graphene surface plasmons (GSPs) in in-plane bended gratings that are formed by elastic vibrations of graphene nanoribbons (GNRs). The gratings enable the light polarized perpendicularly to the GNRs to two kinds of GSP modes, of which the field concentrations are within the grating crest (crest mode, C-M) and trough (trough mode, T-M), respectively. These two kinds of modes will individually cause notches in the transmission spectrum and permit fast off on switching and tuning of their excitation dynamically (elastic vibration, Fermi energy) and geometrically (ribbon width). The performance of this device is analyzed by finite-difference time-domain simulations, which demonstrates a good agreement with the quasi-static analysis theory. The proposed concept expands our understanding of plasmons in GNRs and offers a platform for realizing of 2D graphene plasmonic devices with broadband operations and multichannel modulations. PMID- 26832274 TI - Ultra-thin plasmonic random lasers. AB - An ultrathin plasmonic random laser is fabricated by a simple lift off process, which consists of a free-standing polymer membrane embedded with silver nanoparticles. Low threshold random lasing is observed when the 200-nm-thick membrane device is optically pumped, due to the strong plasmonic feedback and high-quality waveguide confinement provided by the silver nanoparticles and the polymer membrane, respectively. The free-standing polymer membrane is very flexible and transplantable, which can be attached to an optical fiber end face to achieve random lasing. This fabrication technique provides a promising way to realize plasmonic random lasing on surfaces with arbitrary shapes. PMID- 26832275 TI - Cross-phase modulation-induced spectral broadening in silicon waveguides. AB - We analytically and experimentally investigate cross-phase modulation (XPM) in silicon waveguides. In contrast to the well known result in pure Kerr media, the spectral broadening ratio of XPM to self-phase modulation is not two in the presence of either two-photon absorption (TPA) or free carriers. The physical origin of this change is different for each effect. In the case of TPA, this nonlinear absorption attenuates and slightly modifies the pulse shape due to differential absorption in the pulse peak and wings. When free carriers are present two different mechanisms modify the dynamics. First, free-carrier absorption performs a similar role to TPA, but is additionally asymmetric due to the delayed free-carrier response. Second, free-carrier dispersion induces an asymmetric blue phase shift which competes directly with the symmetric Kerr induced XPM red shift. We confirm this analysis with pump-probe experiments in a silicon photonic crystal waveguide. PMID- 26832276 TI - Systematic analysis of optical gradient force in photonic crystal nanobeam cavities. AB - In this work, we provide systematic analysis of the optical force for a particle trapped in the waveguide/cavity/waveguide system. The theoretical analysis shows that the optical trapping force is proportional to QT1/2/V for the particle at a fixed position. We provide numerical proof for the proposed principles and systematically optimize the design recipe to investigate optical tapping force of photonic crystal (PhC) nanobeam cavities. The numerical results are in accordance with theoretical analysis and show that the maximum optical trapping force for a particle occurs at the transmission of cavity around 0.25 and the maxima are almost the same for different PhC cavities. PMID- 26832277 TI - Ray-based optical design tool for freeform optics: coma full-field display. AB - The field of optical fabrication has progressed to a point where manufacturing optical quality freeform surfaces is no longer prohibitive. However, to stimulate the development of freeform systems, optical designers must be provided with the necessary tools. Full-field displays are an example of such a tool. Identifying the field dependence of the dominant aberrations of a freeform system is critical for a controlled optimization and with the help of full-field displays, this can be accomplished. Of specific interest is coma, an often system-limiting aberration and an aberration that has recently been directly addressed with freeform surfaces. In this research, we utilize nodal aberration theory to develop a ray-based method to generate a coma full-field display that circumvents wavefront fitting errors that can affect Zernike polynomial-based full-field displays for highly aberrated freeform starting designs. PMID- 26832278 TI - Five-lens, easy-to-implement miniature objective for a fluorescence confocal microendoscope. AB - A fluorescence confocal microendoscope requires a high-performance miniature objective. We present a miniature objective comprising four glass lenses and one plastic aspheric lens. The 0.5 NA objective is achromatized in the wavelength range of 488-550 nm, has a field of view (FOV) of 360 MUm, and an outer diameter of 2.6 mm. The assembled miniature objective can resolve features separated by as little as 0.78 MUm. The imaging quality of the fluorescence confocal microendoscope with the miniature objective is similar to that of a commercial confocal microscope. It can resolve cellular structures such as crypt structures and epithelial cells. PMID- 26832280 TI - Optical multiple-image encryption based on the chaotic structured phase masks under the illumination of a vortex beam in the gyrator domain. AB - A novel multiple-image encryption scheme using the nonlinear iterative phase retrieval algorithm in the gyrator transform domain under the illumination of an optical vortex beam is proposed. In order to increase the randomness, the chaotic structured phase mask based on the logistic map, Fresnel zone plate and radial Hilbert mask is proposed. With the help of two chaotic phase masks, each plain image is encoded into two phase-only masks that are considered as the private keys by using the iterative phase retrieval process in the gyrator domain. Then, the second keys of all plain images are modulated into the ciphertext, which has the stationary white noise distribution. Due to the use of the chaotic structured phase masks, the problem of axis alignment in the optical setup can easily be solved. Two private keys are directly relative to the plain images, which makes that the scheme has high resistance against various potential attacks. Moreover, the use of the vortex beam that can integrates more system parameters as the additional keys into one phase mask can improve the security level of the cryptosystem, which makes the key space enlarged widely. Simulation results are given to verify the feasibility and robustness of the proposed encryption scheme. PMID- 26832279 TI - Dispersion-based stimulated Raman scattering spectroscopy, holography, and optical coherence tomography. AB - Stimulated Raman scattering (SRS) enables fast, high resolution imaging of chemical constituents important to biological structures and functional processes, both in a label-free manner and using exogenous biomarkers. While this technology has shown remarkable potential, it is currently limited to point scanning and can only probe a few Raman bands at a time (most often, only one). In this work we take a fundamentally different approach to detecting the small nonlinear signals based on dispersion effects that accompany the loss/gain processes in SRS. In this proof of concept, we demonstrate that the dispersive measurements are more robust to noise compared to amplitude-based measurements, which then permit spectral or spatial multiplexing (potentially both, simultaneously). Finally, we illustrate how this method may enable different strategies for biochemical imaging using phase microscopy and optical coherence tomography. PMID- 26832281 TI - Electrically tunable liquid crystal laser using a nanoimprinted indium-tin-oxide electrode as a distributed feedback resonator. AB - We demonstrated electrical tunability of a liquid crystal (LC) laser using a nanoimprinted indium-tin-oxide (ITO) film as a distributed feedback (DFB) resonator, a transparent electrode, and an alignment layer for LCs. From the field-induced reorientation of LCs and changes in effective refractive indices of guided laser modes, lasing emission is tuned by 6 nm at low applied voltage of 8.0 V. This is because the LC laser with the nanoimprinted ITO electrode has no additional insulating layers for lasing performance. The present system is based on the functional electrode and its active control provides various applications and advances in laser technology. PMID- 26832282 TI - Thermomagnetic writing into magnetophotonic microcavities controlling thermal diffusion for volumetric magnetic holography. AB - Holographic memory is expected to become a high-capacity data storage. Magnetic volumetric holograms are rewritable holograms that are recorded as magnetization directions through thermomagnetic recording. However, the effective depth of magnetic holograms is limited by thermal diffusion that causes merging of magnetic fringes. In this study, we propose the insertion of heat-sink layers (HSLs) for retaining well-defined magnetic fringes during volumetric writing. Magnetophotonic microcavity media were used for demonstrating the HSL effect, and the structural design principle was established in numerical calculations. The results indicate that deep and clear magnetic fringes and an improvement in the diffraction efficiency can be achieved by the insertion of HSLs. PMID- 26832283 TI - On-chip data exchange for mode division multiplexed signals. AB - Data exchange is an important function for flexible optical network, and it has been extensively investigated for the time and wavelength domains. The mode division multiplexing (MDM) has been proposed to further increase the transmission capacity by carrying information on different modes with only single wavelength carrier. We propose and experimentally demonstrate a novel on-chip data exchange circuit for the MDM signals by utilizing two micro-ring resonator (MRR) based mode converters. For demonstration, single and four wavelengths non return-to-zero on-off-keying (NRZ-OOK) signals at 10 Gb/s carried on different modes are successfully processed, with open and clear eye diagrams. Measured bit error ratio (BER) results show reasonable power penalties. The proposed circuit can be potentially used in advanced and flexible MDM optical networks. PMID- 26832284 TI - High quality factor nanophotonic resonators in bulk rare-earth doped crystals. AB - Numerous bulk crystalline materials exhibit attractive nonlinear and luminescent properties for classical and quantum optical applications. A chip-scale platform for high quality factor optical nanocavities in these materials will enable new optoelectronic devices and quantum light-matter interfaces. In this article, photonic crystal nanobeam resonators fabricated using focused ion beam milling in bulk insulators, such as rare-earth doped yttrium orthosilicate and yttrium vanadate, are demonstrated. Operation in the visible, near infrared, and telecom wavelengths with quality factors up to 27,000 and optical mode volumes close to one cubic wavelength is measured. These devices enable new nanolasers, on-chip quantum optical memories, single photon sources, and non-linear devices at low photon numbers based on rare-earth ions. The techniques are also applicable to other luminescent centers and crystal. PMID- 26832285 TI - Sensitive method for measuring third order nonlinearities in compact dielectric and hybrid plasmonic waveguides. AB - We demonstrate a sensitive method for the nonlinear optical characterization of micrometer long waveguides, and apply it to typical silicon-on-insulator nanowires and to hybrid plasmonic waveguides. We demonstrate that our method can detect extremely small nonlinear phase shifts, as low as 7.5.10<(-4) rad. The high sensitivity achieved imparts an advantage when investigating the nonlinear behavior of metallic structures as their short propagation distances complicates the task for conventional methods. Our results constitute the first experimental observation of chi((3)) nonlinearities in the hybrid plasmonic platform and is important to test claims of hybrid plasmonic structures as candidates for efficient nonlinear optical devices. PMID- 26832286 TI - 1 Gbps full-duplex links for ultra-dense-WDM 6.25 GHz frequency slots in optical metro-access networks. AB - 1 Gbps full-duplex optical links for 6.25 GHz ultra dense WDM frequency slots are demonstrated and optimized for cost-effective metro-access networks. The OLT-ONU downlinks are based on 1 Gbps Nyquist-DPSK using MZM and single-detector heterodyne reception obtaining a sensitivity of -52 dBm. The ONU-OLT uplinks are based on 1 Gbps NRZ-DPSK by directly phase modulated DFB and also single-detector heterodyne reception obtaining same sensitivity of -52 dBm. The power budget of full-duplex link is 43 dB. These proposed links can provide service to 16 (32) users at each 100 (200) GHz WDM channel. PMID- 26832287 TI - Millimeter-wave imaging with slab focusing lens made of electromagnetic-induction materials. AB - A slab focusing lens in this work has been designed, which consists of electromagnetic-induction materials (cage-shaped granules of conductor materials) and polymethyl methacrylate (PMMA) materials. A compound lens with a thickness of 32 mm is composed of two slab focusing lenses, and has a refractive index of 1.41 at 35 GHz. Millimeter-wave (MMW) images of metallic objects have been obtained with the compound lens. The image quality has been compared by means of the compound lens and the polyethylene lens. The experimental results show good feasibility of the compound lens in MMW imaging. PMID- 26832288 TI - LED light with enhanced color saturation and improved white light perception. AB - The light emitting diodes (LEDs) with high light quality were investigated to enhance the color appearance of the illuminated objects and increase the white light perception of the ambience. The spectral power distributions of the LED lights were optimized by addition of the RGB components and by shifting the color coordinate below the blackbody line to get desired color rendering index (CRI) and high gamut area index (GAI). The results of the human factor study reveal that the "perfect" white light can be achieved to both enhance color saturation and improve light visual impression. The effects of observer metamerism were studied to clarify the observed phenomenon that the white lights with the same color coordinates were perceived differently by real observers. PMID- 26832289 TI - Increasing robustness of bipolar pulse coding in Brillouin distributed fiber sensors. AB - The robustness of bipolar pulse coding against pump depletion issues in Brillouin distributed fiber sensors is theoretically and experimentally investigated. The presented analysis points out that the effectiveness of bipolar coding in Brillouin sensing can be highly affected by the power unbalance between -1's and + 1's elements resulting from depletion and amplification of coded pump pulses. In order to increase robustness against those detrimental effects and to alleviate the probe power limitation imposed by pump depletion, a technique using a three-tone probe is proposed. Experimental results demonstrate that this method allows increasing the probe power by more than 12.5 dB when compared to the existing single-probe tone implementation. This huge power increment, together with the 13.5 dB signal-to-noise enhancement provided by 512-bit bipolar Golay codes, has led to low-uncertainty measurements (< 0.9 MHz) of the local Brillouin peak gain frequency over a real remoteness of 100 km, using a 200 km-long fiber loop and 2 m spatial resolution. The method is evaluated with a record figure-of merit of 380'000. PMID- 26832290 TI - Precise measurement of orientations of transparent ellipsoidal particles through digital holographic microscopy. AB - A method to measure the orientations of transparent ellipsoidal particles using digital holographic microscopy (DHM) is proposed in this study. This approach includes volumetric recording and numerical reconstruction at different depths. Distinctive light scatterings from an ellipsoid with different angles of orientation are analyzed. A focus function is applied to obtain a reconstructed image that contains a bright line parallel to the major axis of the projected particle, which provides in-plane orientation information. An intensity profile is collected along the major axis of the projected particle in the direction of the optical axis, and this profile is then utilized to measure the out-of-plane orientation of the ellipsoid. After being verified for an ellipsoid with known orientations, the proposed method is applied to ellipsoids suspended in a pipe flow with random orientations. This DHM method can extract the essential information of ellipsoids and therefore has great potential applications in particle dynamics. PMID- 26832291 TI - Polarization mode coupling and related effects in fiber Bragg grating inscribed in polarization maintaining fiber. AB - Polarization mode coupling (PMC) and related effects from writing fiber Bragg gratings in polarization maintaining fiber (FBGs-in-PMF) are observed experimentally for the first time by optical fiber coherence domain polarimetry (OCDP) using a broadband light source. PMC is another useful aspect of FBG-in-PMF besides Bragg wavelength and its possible potential is evaluated and discussed. A localized and long range temperature measurement based on the PMC and Bragg wavelength is given as an example. PMID- 26832292 TI - Ice cloud backscatter study and comparison with CALIPSO and MODIS satellite data. AB - An invariant imbedding T-matrix (II-TM) method is used to calculate the single scattering properties of 8-column aggregate ice crystals. The II-TM based backscatter values are compared with those calculated by the improved geometric optics method (IGOM) to refine the backscattering properties of the ice cloud radiative model used in the MODIS Collection 6 cloud optical property product. The integrated attenuated backscatter-to-cloud optical depth (IAB-ICOD) relation is derived from simulations using a CALIPSO (Cloud-Aerosol Lidar and Infrared Pathfinder Satellite) lidar simulator based on a Monte Carlo radiative transfer model. By comparing the simulation results and co-located CALIPSO and MODIS (Moderate Resolution Imaging Spectroradiometer) observations, the non-uniform zonal distribution of ice clouds over ocean is characterized in terms of a mixture of smooth and rough ice particles. The percentage of the smooth particles is approximately 6% and 9% for tropical and midlatitude ice clouds, respectively. PMID- 26832293 TI - Electrostatically tunable plasmonic devices fabricated on multi-photon polymerized three-dimensional microsprings. AB - Electrostatically tunable plasmonic devices on three-dimensional (3D) microsprings were fabricated using multi-photon polymerization followed by metal deposition. These plasmonic devices comprised a nanostructured Au microplate and two 3D microsprings. The maximum plasmon excitation efficiency was 35%, a value achieved with incident light of wavelength 632.8 nm. The efficiency could be continuously changed from almost zero to maximum by inclining the microplates with the application of DC voltage up to 50 V. Such dynamic functionality is useful for the realization of highly integrated optoelectronic devices and tunable metamaterials. PMID- 26832294 TI - Highly-sensitive magnetic field sensor based on fiber ring laser. AB - A highly sensitive magnetic field sensor based on a fiber ring laser has been proposed and experimentally demonstrated. The magnetic field sensor was fabricated by introducing a rotary apparatus modulated by an external magnetic field into the fiber cavity to twist one section of the fiber. Due to the remarkable birefringence change induced into the laser cavity, the beat frequency generated between two polarizations of the laser is sensitive to the variation of applied magnetic field intensity. Experimental results show that the polarization mode beat frequency linearly shifts with the increment of the magnetic field intensity and the sensitivity reaches up to 7.09 KHz/Oe in the range of 0 - 437 Oe. Therefore, it will be a promising candidate for the weak magnetic field applications including military, hazard forecast and biomedical fields. PMID- 26832295 TI - Single-channel 40 Gbit/s digital coherent QAM quantum noise stream cipher transmission over 480 km. AB - We demonstrate the first 40 Gbit/s single-channel polarization-multiplexed, 5 Gsymbol/s, 16 QAM quantum noise stream cipher (QNSC) transmission over 480 km by incorporating ASE quantum noise from EDFAs as well as the quantum shot noise of the coherent state with multiple photons for the random masking of data. By using a multi-bit encoded scheme and digital coherent transmission techniques, secure optical communication with a record data capacity and transmission distance has been successfully realized. In this system, the signal level received by Eve is hidden by both the amplitude and the phase noise. The highest number of masked signals, 7.5 x 10(4), was achieved by using a QAM scheme with FEC, which makes it possible to reduce the output power from the transmitter while maintaining an error free condition for Bob. We have newly measured the noise distribution around I and Q encrypted data and shown experimentally with a data size of as large as 2(25) that the noise has a Gaussian distribution with no correlations. This distribution is suitable for the random masking of data. PMID- 26832296 TI - 3.36 um single-mode quantum cascade laser with a dissipation below 250 mW. AB - We present 3.36 um buried heterostructure distributed-feedback quantum cascade lasers with a power dissipation at threshold below 250 mW and operation temperatures as high as 130 degrees C. Threshold values below 20 mA at -10 degrees C in pulsed operation and 30 mA at -20 degrees C in continuous-wave operation are reported. Optical power above 130 mW and 13 mW are achieved at -20 degrees C in pulsed and continuous-wave operation, respectively. Continuous-wave operation occurs until 15 degrees C. We show single-mode emission in pulsed and continuous-wave operation. Single-mode performance is demonstrated in long pulse (5.56 us) operation. The laser far-field exhibits a single lobe emission with full-width-half-max of 27 degrees * 34 degrees . PMID- 26832297 TI - Full-mesh T- and O-band wavelength router based on arrayed waveguide gratings. AB - We propose an ultra-broadband full-mesh wavelength router supporting the T- and O bands using 3 stages of cascaded arrayed waveguide gratings (AWGs). The router architecture is based on a combination of waveband and channel routing by coarse and fine AWGs, respectively. We fabricated several T-band-specific silica-based AWGs and quantum dot semiconductor optical ampliers as part of the router, and demonstrated 10 Gbps data transmission for several wavelengths throughout a range of 7.4 THz. The power penalties were below 1 dB. Wavelength routing was also demonstrated, where tuning time within a 9.4-nm-wide waveband was below 400 ms. PMID- 26832298 TI - Thermal tuning of Kerr frequency combs in silicon nitride microring resonators. AB - Microresonator based Kerr frequency comb generation has many attractive features, including ultrabroad spectra, chip-level integration, and low power consumption. Achieving precise tuning control over the comb frequencies will be important for a number of practical applications, but has been little explored for microresonator combs. In this paper, we characterize the thermal tuning of a coherent Kerr frequency comb generated from an on-chip silicon nitride microring. When the microring temperature is changed by ~70 degrees C with an integrated microheater, the line spacing and center frequency of the comb are tuned respectively by -253 MHz (-3.57 MHz/ degrees C) and by -175 GHz (-2.63 GHz/ degrees C); the latter constitutes 75% of the comb line spacing. From these results we obtain a shift of 25 GHz (362.07 MHz/ degrees C) in the comb carrier envelope offset frequency. Numerical simulations are performed by taking into account the thermo-optic effects in the waveguide core and cladding. The temperature variation of the comb line spacing predicted from simulations is close to that observed in experiments. The time-dependent thermal response of the microheater based tuning scheme is characterized; time constants of 30.9 MUs and 0.71 ms are observed. PMID- 26832299 TI - Fabrication, characterization and applications of flexible vertical InGaN micro light emitting diode arrays. AB - Flexible vertical InGaN micro-light emitting diode (micro-LED) arrays have been fabricated and characterized for potential applications in flexible micro displays and visible light communication. The LED epitaxial layers were transferred from initial sapphire substrates to flexible AuSn substrates by metal bonding and laser lift off techniques. The current versus voltage characteristics of flexible micro-LEDs degraded after bending the devices, but the electroluminescence spectra show little shift even under a very small bending radius 3 mm. The high thermal conductivity of flexible metal substrates enables high thermal saturation current density and high light output power of the flexible micro-LEDs, benefiting the potential applications in flexible high brightness micro-displays and high-speed visible light communication. We have achieved ~40 MHz modulation bandwidth and 120 Mbit/s data transmission speed for a typical flexible micro-LED. PMID- 26832300 TI - Nonlinear optics of surface plasmon polaritons in subwavelength graphene ribbon resonators. AB - We study the propagation characteristics of surface Plasmon polaritons (SPPs) on a patterned graphene sheet incorporating a subwavelength ribbon resonator and a Kerr nonlinear bounding medium (substrate or top cladding) which provides tunable bandpass filtering in the THz regime. We study theoretically and via modeling the tunability of maxima in the transmission spectrum, corresponding to the resonant frequencies of the ribbon resonator, by tuning the graphene Fermi level (via an applied gate voltage) and by altering the intensity of the incident THz wave. We determine the intensity-dependent increase in the refractive index of a Kerr nonlinear medium bounding graphene, via self-phase modulation and via the more efficient process of cross-phase modulation, revealing a noticeable red-shift in the resonant frequencies of the ribbon resonator. These concepts lead to ultrafast switching of SPP transmission through the ribbon (from a high to a low state). Using Kerr nonlinear media to bound graphene increases the tunability of graphene-based devices, enabling nonlinear plasmonic and ultrafast processing in the THz regime. PMID- 26832301 TI - Disposable gold coated pyramidal SERS sensor on the plastic platform. AB - In this paper we investigate suitability of arrays of gold coated pyramids for surface-enhanced Raman scattering (SERS) sensing applications. Pyramidarrays composed of 1000 nm pit size with 1250 nm pitch lengthwerereplicated on a plastic substrate by roll-to-roll (R2R) ultraviolet (UV) embossing. The level of SERS enhancement, and qualitative performance provided by the new substrate is investigated by comparing Raman spectrum of benzenethiol (BTh) test molecules to the benchmark Klarite SERS substrate which comprises inverted pyramid arrays(1500 nm pit size with 2000 nm pitch length) fabricated on a silicon substrate. The new substrate is found to provide upto 11 times increase in signal in comparison to the inverted pyramid (IV-pyramid) arrays fabricated on an identical plastic substrate. Numerical simulation and experimental evidence suggest that strongly confined electromagnetic fields close to the base of the pyramids, are mainly responsible for the Raman enhancement factor, instead of the fields localized around the tip. Unusually strong plasmon fields are projected upto 200nm from the sidewalls at the base of the pyramid increasing the cross sectional sensing volume. PMID- 26832302 TI - Hierarchy of cellular decisions in collective behavior: Implications for wound healing. AB - Collective processes such as wound re-epithelialization result from the integration of individual cellular decisions. To determine which individual cell behaviors represent the most promising targets to engineer re-epithelialization, we examined collective and individual responses of HaCaT keratinocytes seeded upon polyacrylamide gels of three stiffnesses (1, 30, and 100 kPa) and treated with a range of epidermal growth factor (EGF) doses. Wound closure was found to increase with substrate stiffness, but was responsive to EGF treatment only above a stiffness threshold. Individual cell behaviors were used to create a partial least squares regression model to predict the hierarchy of factors driving wound closure. Unexpectedly, cell area and persistence were found to have the strongest correlation to the observed differences in wound closure. Meanwhile, the model predicted a relatively weak correlation between wound closure with proliferation, and the unexpectedly minor input from proliferation was successfully tested with inhibition by aphidicolin. Combined, these results suggest that the poor clinical results for growth factor-based therapies for chronic wounds may result from a disconnect between the individual cellular behaviors targeted in these approaches and the resulting collective response. Additionally, the stiffness-dependency of EGF sensitivity suggests that therapies matched to microenvironmental characteristics will be more efficacious. PMID- 26832304 TI - Pulp science: education and communication in the paperback book revolution. AB - Paperback books on scientific topics were a hot commodity in the United States from the 1940s to 1960s providing a vehicle for science communication that transformed science education. Well-known scientists authored them, including Rachel Carson, Theodosius Dobzhansky, George Gamow, Fred Hoyle, Julian Huxley, and Margaret Mead. A short history of 'the paperback revolution' that began in the 1930s is provided before concentrating on one publishing company based in New York City, the New American Library of World Literature (NAL), which produced Signet and Mentor Books. The infrastructure that led to the production and consumption of paperback books is described and an underexplored and not previously identified genre of educational books on scientific topics, what the author refers to as pulp science, is characterized. PMID- 26832303 TI - alpha1A-Adrenergic receptor prevents cardiac ischemic damage through PKCdelta/GLUT1/4-mediated glucose uptake. AB - While alpha(1)-adrenergic receptors (ARs) have been previously shown to limit ischemic cardiac damage, the mechanisms remain unclear. Most previous studies utilized low oxygen conditions in addition to ischemic buffers with glucose deficiencies, but we discovered profound differences if the two conditions are separated. We assessed both mouse neonatal and adult myocytes and HL-1 cells in a series of assays assessing ischemic damage under hypoxic or low glucose conditions. We found that alpha(1)-AR stimulation protected against increased lactate dehydrogenase release or Annexin V(+) apoptosis under conditions that were due to low glucose concentration not to hypoxia. The alpha(1)-AR antagonist prazosin or nonselective protein kinase C (PKC) inhibitors blocked the protective effect. alpha(1)-AR stimulation increased (3)H-deoxyglucose uptake that was blocked with either an inhibitor to glucose transporter 1 or 4 (GLUT1 or GLUT4) or small interfering RNA (siRNA) against PKCdelta. GLUT1/4 inhibition also blocked alpha(1)-AR-mediated protection from apoptosis. The PKC inhibitor rottlerin or siRNA against PKCdelta blocked alpha(1)-AR stimulated GLUT1 or GLUT4 plasma membrane translocation. alpha(1)-AR stimulation increased plasma membrane concentration of either GLUT1 or GLUT4 in a time-dependent fashion. Transgenic mice overexpressing the alpha(1A)-AR but not alpha(1B)-AR mice displayed increased glucose uptake and increased GLUT1 and GLUT4 plasma membrane translocation in the adult heart while alpha(1A)-AR but not alpha(1B)-AR knockout mice displayed lowered glucose uptake and GLUT translocation. Our results suggest that alpha(1)-AR activation is anti-apoptotic and protective during cardiac ischemia due to glucose deprivation and not hypoxia by enhancing glucose uptake into the heart via PKCdelta-mediated GLUT translocation that may be specific to the alpha(1A)-AR subtype. PMID- 26832305 TI - Photonic-assisted microwave signal multiplication and modulation using a silicon Mach-Zehnder modulator. AB - Photonic generation of microwave signal is obviously attractive for many prominent advantages, such as large bandwidth, low loss, and immunity to electromagnetic interference. Based on a single integrated silicon Mach-Zehnder modulator (MZM), we propose and experimentally demonstrate a simple and compact photonic scheme to enable frequency-multiplicated microwave signal. Using the fabricated integrated MZM, we also demonstrate the feasibility of microwave amplitude-shift keying (ASK) modulation based on integrated photonic approach. In proof-of-concept experiments, 2-GHz frequency-doubled microwave signal is generated using a 1-GHz driving signal. 750-MHz/1-GHz frequency tripled/quadrupled microwave signals are obtained with a driving signal of 250 MHz. In addition, a 50-Mb/s binary amplitude coded 1-GHz microwave signal is also successfully generated. PMID- 26832306 TI - Evolutionary dynamics and biogeography of Musaceae reveal a correlation between the diversification of the banana family and the geological and climatic history of Southeast Asia. AB - Tropical Southeast Asia, which harbors most of the Musaceae biodiversity, is one of the most species-rich regions in the world. Its high degree of endemism is shaped by the region's tectonic and climatic history, with large differences between northern Indo-Burma and the Malayan Archipelago. Here, we aim to find a link between the diversification and biogeography of Musaceae and geological history of the Southeast Asian subcontinent. The Musaceae family (including five Ensete, 45 Musa and one Musella species) was dated using a large phylogenetic framework encompassing 163 species from all Zingiberales families. Evolutionary patterns within Musaceae were inferred using ancestral area reconstruction and diversification rate analyses. All three Musaceae genera - Ensete, Musa and Musella - originated in northern Indo-Burma during the early Eocene. Musa species dispersed from 'northwest to southeast' into Southeast Asia with only few back dispersals towards northern Indo-Burma. Musaceae colonization events of the Malayan Archipelago subcontinent are clearly linked to the geological and climatic history of the region. Musa species were only able to colonize the region east of Wallace's line after the availability of emergent land from the late Miocene onwards. PMID- 26832307 TI - Pseudomonas aeruginosa Colonization in the Intensive Care Unit: Prevalence, Risk Factors, and Clinical Outcomes. AB - OBJECTIVE: To determine the prevalence of Pseudomonas aeruginosa colonization on intensive care unit (ICU) admission, risk factors for P. aeruginosa colonization, and the incidence of subsequent clinical culture with P. aeruginosa among those colonized and not colonized. METHODS: We conducted a cohort study of patients admitted to a medical or surgical intensive care unit of a tertiary care hospital. Patients had admission perirectal surveillance cultures performed. Risk factors analyzed included comorbidities at admission, age, sex, antibiotics received during current hospitalization before ICU admission, and type of ICU. RESULTS: Of 1,840 patients, 213 (11.6%) were colonized with P. aeruginosa on ICU admission. Significant risk factors in the multivariable analysis for colonization were age (odds ratio, 1.02 [95% CI, 1.01-1.03]), anemia (1.90 [1.05 3.42]), and neurologic disorder (1.80 [1.27-2.54]). Of the 213 patients colonized with P. aeruginosa on admission, 41 (19.2%) had a subsequent clinical culture positive for P. aeruginosa on ICU admission and 60 (28.2%) had a subsequent clinical culture positive for P. aeruginosa in the current hospitalization (ICU period and post-ICU period). Of these 60 patients, 49 (81.7%) had clinical infections. Of the 1,627 patients not colonized on admission, only 68 (4.2%) had a subsequent clinical culture positive for P. aeruginosa in the current hospitalization. Patients colonized with P. aeruginosa were more likely to have a subsequent positive clinical culture than patients not colonized (incidence rate ratio, 6.74 [95% CI, 4.91-9.25]). CONCLUSIONS: Prediction rules or rapid diagnostic testing will help clinicians more appropriately choose empirical antibiotic therapy for subsequent infections. PMID- 26832308 TI - Temporal changes in allele frequencies in a small marble trout Salmo marmoratus population threatened by extreme flood events. AB - The effect of extreme floods on the genetic composition of marble trout Salmo marmoratus living in Lipovscek, a tributary of the Soca River in Slovenia, which has been affected by multiple destructive flood events for centuries was investigated. By monitoring genetic variability during the period 2004-2011, apparent signatures of genetic erosion including a decline in observed and expected heterozygosities and allelic richness were observed. Contemporary effective population size was estimated between 11 and 55 individuals, which is congruent with census data. The data suggest asymmetric gene flow between the two sections of the river. The existence of substantial downstream migration (15-19%) was confirmed by paternity analysis. A small (1-3%) upstream migration was also suggested, which was confirmed by tagging data. Overall, low genetic diversity has not prevented the survival of the Lipovscek population, which might be a common feature of salmonid freshwater populations. PMID- 26832309 TI - Liver condition of Holstein cows affects mitochondrial function and fertilization ability of oocytes. AB - The aim of the present study was to examine the fertilization ability and mitochondrial function of oocytes derived from cows with or without liver damage. Oocytes were collected from the ovaries of cows with damaged livers (DL) and those of cows with healthy livers (HL), subjected to in vitro maturation, and fertilized in vitro. A significantly high abnormal fertilization rate was observed for oocytes from DL cows compared to oocytes from HL cows. The time to dissolve the zona pellucida by protease before fertilization was similar between the two liver conditions, whereas after fertilization treatment this time was shorter for DL cows than for HL cows. The percentage of oocytes with equivalent cortical granule distributions underneath the membrane was greater for in vitro matured oocytes from HL cows, whereas an immature distribution pattern was observed for oocytes from DL cows. In addition, a greater percentage of oocytes derived from HL cows released cortical granules following fertilization compared with oocytes from DL cows. Mitochondrial function determined by ATP content and membrane potential were similar at the germinal vesicle stage, but post-in vitro maturation, the oocytes derived from HL cows showed higher values than DL cows. The mitochondrial DNA copy number in oocytes was similar between the two liver conditions for both the germinal vesicle and post-in vitro maturation oocytes. In conclusion, liver damage induces low fertilization, likely because of incomplete cortical granule distribution and release, and the maturation of oocytes from DL cows contain low-functioning mitochondria compared to their HL counterparts. PMID- 26832310 TI - Effects of Hand Fellowship Training on Rates of Endoscopic and Open Carpal Tunnel Release. AB - PURPOSE: To investigate rates, trends, and complications for carpal tunnel release (CTR) related to fellowship training using the American Board of Orthopaedic Surgery Part II Database. METHODS: We searched the American Board of Orthopaedic Surgery database for patients with carpal tunnel syndrome who underwent either open carpal tunnel release (OCTR) or endoscopic (ECTR) from 2003 to 2013. Cases with multiple treatment codes were excluded. Data were gathered on geographic location, fellowship, and surgical outcomes. Data were then divided into 2 cohorts: hand fellowship trained versus non-hand fellowship trained. We performed analysis with chi-square tests of independence and for trend. RESULTS: Overall, 12.4% of all CTRs were done endoscopically. Hand fellowship-trained orthopedists performed about 4.5 times the number of ECTR than did non-hand fellowship-trained surgeons. An increasing trend over time of ECTR was seen only among the hand fellowship cohort. The northwest region of the United States had the highest incidence (23.1%) of ECTR, and the Southwest the lowest incidence (5.9%). The complication incidence associated with CTR overall was 3.6%, without a significant difference between ECTR and OCTR. Within the hand fellowship cohort the complication incidence for ECTR was significantly less than for OCTR. There was no difference in overall complication rates with ECTR and OCTR between the 2 cohorts. Wound complications were higher with OCTR (1.2% vs 0.25%) and nerve palsy with ECTR (0.66% vs 0.27%); with postoperative pain equivalent between techniques independent of fellowship training. CONCLUSIONS: Within the United States from 2003 to 2013, the rate of ECTR increased, as did complications. However, complication rates remained low in the first 2 years of practice. Hand fellowship-trained surgeons performed more ECTR than did non-hand fellowship trained orthopedic surgeons, and both groups had similar complication rates. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26832311 TI - Real Time Imaging of Deuterium in a Duplex Stainless Steel Microstructure by Time of-Flight SIMS. AB - For more than one century, hydrogen assisted degradation of metallic microstructures has been identified as origin for severe technical component failures but the mechanisms behind have not yet been completely understood so far. Any in-situ observation of hydrogen transport phenomena in microstructures will provide more details for further elucidation of these degradation mechanisms. A novel experiment is presented which is designed to elucidate the permeation behaviour of deuterium in a microstructure of duplex stainless steel (DSS). A hydrogen permeation cell within a TOF-SIMS instrument enables electrochemical charging with deuterium through the inner surface of the cell made from DSS. The outer surface of the DSS permeation cell exposed to the vacuum has been imaged by TOF-SIMS vs. increasing time of charging with subsequent chemometric treatment of image data. This in-situ experiment showed evidently that deuterium is permeating much faster through the ferrite phase than through the austenite phase. Moreover, a direct proof for deuterium enrichment at the austenite-ferrite interface has been found. PMID- 26832312 TI - Assessment of mitral valve morphology using three-dimensional echocardiography. Feasibility and reference values. AB - OBJECTIVES: To evaluate the feasibility of real time transthoracic three dimensional echocardiography (RT3DE) for evaluation of normal canine mitral valves (MVs), and to provide reference values for this technique. ANIMALS: Forty three cardiologically healthy, not sedated dogs. METHODS: Transthoracic RT3DE mitral datasets were acquired during two consecutive 6-month periods. The datasets were analyzed using commercially available software. An MV model was drawn using a semiautomated procedure and MV variables were obtained and calculated. The ratio between annulus height and commissural diameter was used as an index of the annulus' saddle-shaped non-planarity. After evaluation of associations between measured variables and body size, the datasets were used to generate reference intervals. Coefficients of variation (CVs), variance components, and repeatability coefficients were calculated for the evaluation of intra-observer, inter-observer, and day-to-day variability. RESULTS: Datasets could be analyzed in 34 of 43 (79%) dogs. 68 percent of datasets obtained during the first 6-month period could be analyzed and 90% obtained during the second period could be analyzed. An allometric relationship was identified for most MV variables. The MV annulus appeared elliptical and saddle-shaped. Inter- and intra observer CVs were less than 20%. Coefficient of variation greater than 20% was calculated for the inter-day variation for some variables. Operator and observer were primarily responsible for the variation of most of the variables. CONCLUSIONS: Evaluation of canine mitral valves by transthoracic RT3DE is feasible. Canine MVs of healthy dogs analyzed using RT3DE are elliptical and saddle-shaped. Reference intervals for the measured MV variables are proposed. PMID- 26832315 TI - How Are Online Health Messages Processed? Using Eye Tracking to Predict Recall of Information in Younger and Older Adults. AB - Little research has focused on what precedes the processing of health messages to predict recall of information and whether age matters in this regard. To address this gap, this study investigates the relationship between attention and recall among younger (<65 years) and older (>=65 years) adults. Using eye tracking, we exposed participants to a webpage consisting of text-only information, text with cognitive illustrations, or text with affective illustrations. When attention to text increased, older adults recalled more information, whereas younger adults did not. However, younger adults paid more attention to cognitive illustrations than older adults and recalled more information. These results reveal conditions under which health messages are effectively recalled by younger and older adults. PMID- 26832316 TI - [Cost-effectiveness analysis of apixaban versus acetylsalicylic acid in the prevention of stroke in patients with non-valvular atrial fibrillation in Spain]. AB - OBJECTIVE: To assess the cost-effectiveness of apixaban versus acetylsalicylic acid (ASA) in stroke prevention in patients with non-valvular atrial fibrillation (NVAF) with contraindications of vitamin K antagonists in Spain. METHODS: A Markov model was adapted, simulating the patient's lifetime. The safety and efficacy of the drugs were obtained from AVERROES clinical trial. The analysis was done from the Spanish National Health System (NHS) and societal perspective. The cost of drugs was calculated according to the recommended doses. The cost of NVAF complications and disease management was obtained from Spanish sources. RESULTS: In a cohort of 1,000 patients with NVAF, during their lifetime numerous complications could be avoided with apixaban versus ASA (48 ischemic strokes, 10 systemic embolism and 53 related deaths). In each patient treated with apixaban more life-years (0.303 LYG) and more quality-adjusted life-years (0.277 QALYs) could be gained. Apixaban would generate more costs per patient for the NHS (?1,742 per patient) but savings would result from the social perspective (?2,887 saved per patient). The cost per LYG and QALY gained would be of ?5,749 and ?6,289 for the NHS. Apixaban would be dominant (more effective with less costs than ASA) from the societal perspective. The results were stable in both deterministic and probabilistic sensitivity analyses. CONCLUSIONS: According to this model, when costs and estimated lifetime outcomes achieved with apixaban are compared with those of ASA, apixaban was assessed to be a cost-effective treatment for the prevention of stroke in patients with NVAF in Spain. PMID- 26832317 TI - Long-term tolerance of preservative-free eye drops containing macrogol hydroxystearate as an excipient. AB - PURPOSE: This in vivo animal study was conducted to assess the tolerability of macrogloglycerol hydrostearate 40 (MGH 40), commonly used as a solubilizing excipient in prostaglandin F2alpha analogue eye drops without benzalkonium chloride. METHODS: Twenty-eight (14 males and 14 females) New Zealand white albino rabbits in good health and with no signs of ocular irritation were randomly assigned to receive 25 MUL instillations of a solution containing 10% MGH 40 in the right eye 3 times daily for either 3 or 6 months. Ocular examinations of the conjunctiva, cornea and iris (using an ophthalmoscope and slit-lamp), corneal sensitivity, and intraocular pressure were assessed in both the right (treated) and left (untreated) eyes throughout the study. General characteristics, hematology and serum biochemistry parameters were also assessed throughout the study and necropsy examinations were performed at study completion. RESULTS: There were no treatment-related effects on the cornea, conjunctiva, iris, or intraocular pressure. Transient findings were generally seen in the untreated as well as the treated eye. Similarly, there were no treatment-related findings in either the hematology or serum biochemistry data or at necropsy. There were no differences based on gender. CONCLUSIONS: Long-term administration of a 10% MGH 40-containing formulation three times per day in a standard in vivo animal model was well tolerated and had no ocular or other effect. PMID- 26832318 TI - [A rare cause of ophthalmoplegia, report of a case of mycormycosis]. PMID- 26832319 TI - [Eales disease and tuberculosis: A case report]. PMID- 26832320 TI - A Survey to Determine Decision-Making Styles of Working Paramedics and Student Paramedics. AB - OBJECTIVE: Two major processes underlie human decision-making: experiential (intuitive) and rational (conscious) thinking. The predominant thinking process used by working paramedics and student paramedics to make clinical decisions is unknown. METHODS: A survey was administered to ground ambulance paramedics and to primary care paramedic students. The survey included demographic questions and the Rational Experiential Inventory-40, a validated psychometric tool involving 40 questions. Twenty questions evaluated each thinking style: 10 assessed preference and 10 assessed ability to use that style. Responses were provided on a five-point Likert scale, with higher scores indicating higher affinity for the style in question. Analysis included both descriptive statistics and t tests to evaluate differences in thinking style. RESULTS: The response rate was 88.4% (1172/1326). Paramedics (n=904) had a median age of 36 years (IQR 29-42) and most were male (69.5%) and primary or advanced care paramedics (PCP=55.5%; ACP=32.5%). Paramedic students (n=268) had a median age of 23 years (IQR 21-26), most were male (63.1%) and had completed high school (31.7%) or an undergraduate degree (25.4%) prior to paramedic training. Both groups scored their ability to use and favourability toward rational thinking significantly higher than experiential thinking. The mean score for rational thinking was 3.86/5 among paramedics and 3.97/5 among paramedic students (p<0.001). The mean score for experiential thinking was 3.41/5 among paramedics and 3.35/5 among paramedic students (p=0.06). CONCLUSION: Working paramedics and student paramedics prefer and perceive that they have the ability to use rational over experiential thinking. This information adds to our current knowledge on paramedic decision-making and is potentially important for developing continuing education and clinical support tools. PMID- 26832321 TI - Museum perceptions and productions: American migrations of a Maori hei-tiki. AB - Museum objects have biographies shaped by their material, geographical and cultural origins, their initial intended purpose, and the ways in which they are valued and interpreted by curators and public audiences. Often one object becomes highly symbolic of a particular group even as its presentation over time reflects changing perceptions of the culture as well as the individual object. A Maori hei tiki - a small but distinctive greenstone pendant - collected by Charles Wilkes on his United States Exploring Expedition in 1840 provides insight into changing museum practices, museum networks of exchange, the impact of professionalizing expertise in ethnology and anthropology since the late nineteenth century, shifting public interests and expectations, and, indeed, the unanticipated ways in which museum objects find their way into exhibition, in this case at the Smithsonian Institution. The material resilience and embedded historicity of the hei-tiki remain as a counterbalance to its versatility as an object useful in multiple stories over nearly two centuries. PMID- 26832322 TI - Inflammatory response of a prostate stromal cell line induced by Trichomonas vaginalis. AB - While Trichomonas vaginalis, a cause of sexually transmitted infection, is known as a surface-dwelling protozoa, trichomonads have been detected in prostatic tissue from benign prostatic hyperplasia and prostatitis by immunoperoxidase assay or PCR. However, the immune response of prostate stromal cells infected with T. vaginalis has not been investigated. Our objective was to investigate whether T. vaginalis could induce an inflammatory response in prostate stromal cells. Incubation of a human prostate stromal myofibroblast cells (WPMY-1) with live T. vaginalis T016 increased expression of the inflammatory chemokines CXCL8 and CCL2. In addition, TLR4, ROS, MAPK and NF-kappaB expression increased, while inhibitors of TLR4, ROS, MAPKs and NF-kappaB reduced CXCL8 and CCL2 production. Medium conditioned by incubation of WPMY-1 cells with T. vaginalis stimulated the migration of human neutrophils and monocytes (THP-1 cells). We conclude that T. vaginalis increases CXCL8 and CCL2 production by human prostate stromal cells by activating TLR4, ROS, MAPKs and NF-kappaB, and this in turn attracts neutrophils and monocytes and leads to an inflammatory response. This study is the first attempt to demonstrate an inflammatory reaction in prostate stromal cells caused by T. vaginalis. PMID- 26832323 TI - Suppression of P2X7/NF-kappaB pathways by Schisandrin B contributes to attenuation of lipopolysaccharide-induced inflammatory responses in acute lung injury. AB - The aim of the present study was to assess the effects and mechanisms of Schisandrin B (SchB) on lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (1 mg/kg), and SchB (25, 50, and 75 mg/kg) was injected 1 h before LPS challenge by gavage. After 12 h, bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected. Histological studies demonstrated that SchB attenuated LPS-induced interstitial edema, hemorrhage, and infiltration of neutrophils in the lung tissue. SchB pretreatment at doses of 25, 50, and 75 mg/kg was shown to reduce LPS-induced lung wet-to-dry weight ratio and lung myeloperoxidase activity. In addition, pretreatment with SchB lowered the number of inflammatory cells and pro inflammatory cytokines including tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 in BALF. The mRNA and protein expression levels of nuclear factor kappa B (NF-kappaB) signaling-related molecules activated by P2X7 were investigated to determine the molecular mechanism of SchB. The findings presented here suggest that the protective mechanism of SchB may be attributed partly to the decreased production of pro-inflammatory cytokines through the inhibition of P2X7/NF-kappaB activation. PMID- 26832324 TI - Promising anti-diabetic potential of capillin and capillinol isolated from Artemisia capillaris. AB - Caffeoylquinic acids, flavonoids, and coumarins isolated from Artemisia capillaris have recently emerged as therapeutic candidates for diabetes and diabetic complications; however, there have been very few studies of the anti diabetic potential of polyacetylenes. In the present study, we investigated the anti-diabetic potential of two polyacetylenes isolated from A. capillaris, namely capillin and capillinol by investigating their ability to inhibit alpha glucosidase, protein tyrosine phosphatase 1B (PTP1B), and rat lens aldose reductase (RLAR). Capillin displayed potent inhibitory activity against alpha glucosidase, PTP1B, and RLAR, while capillinol showed moderate inhibitory activity against alpha-glucosidase and PTP1B at the concentrations tested. In addition, a kinetic study revealed that capillin inhibited alpha-glucosidase and RLAR in a noncompetitive manner, while inhibited PTP1B in a mixed-type manner. Capillinol inhibited alpha-glucosidase and PTP1B in a mixed-type manner. Docking simulations of these compounds demonstrated negative binding energies and close proximity to residues in the binding pocket of PTP1B, indicating that these polyacetylenes have a high affinity and tight binding capacity for the active site of the enzyme. Furthermore, capillin dose-dependently inhibited peroxynitrite (ONOO(-))-mediated tyrosine nitration. The results clearly demonstrate the promising potential of capillin and capillinol as therapeutic interventions for the management of diabetes as well as diabetes-associated complications. PMID- 26832325 TI - Antiinflammatory and analgesic effects of Eurycoma longifolia extracts. AB - Eurycoma longifolia is one of the most popular herbal medicines in Southeast Asia. The purpose of this study is to evaluate the analgesic and anti inflammatory effects of the methanolic extract of E. longifolia roots (TA) in vivo and to investigate the underlying mechanisms. TA was tested for analgesic activity by the hot plate test and acetic acid test in mice. The anti inflammatory effect of TA was observed in carrageenan-induced paw edema in mice. The in vitro molecular study using macrophage cells was performed to elucidate the relevant mechanism. The analgesic activity of 400 mg/kg TA was higher than that of aspirin in the hot plate test. TA also showed analgesic effects in the acetic acid test in a dose-dependent manner. In carrageenan-induced edema in mice, TA showed an anti-inflammatory effect comparable to that of diclofenac. Further in vitro molecular study using macrophage cells revealed that TA suppressed NF-kappaB translocation to the nucleus, leading to inactivation of the NF-kappaB signaling pathway and reduction in the expression of cyclooxygenase-2 and inducible nitric oxide synthase. These results exhibited the beneficial effects of TA for alleviating pain and inflammation, which were exerted through inactivation of the NF-kappaB signaling pathway. PMID- 26832326 TI - Neuroprotective effects of (-)-linalool against oxygen-glucose deprivation induced neuronal injury. AB - (-)-Linalool, a major component of many essential oils, is widely used in cosmetics and flavoring ingredients as well as in traditional medicines. Although various in vitro and in vivo studies have shown that (-)-linalool has anti convulsant, anti-nociceptive, anti-inflammatory and anti-oxidative properties, its anti-ischemic/hypoxic effects have yet to be determined. This study assessed the neuroprotective effects of (-)-linalool against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced cortical neuronal injury, an in vitro model of ischemic stroke. (-)-Linalool significantly attenuated OGD/R-evoked cortical neuronal injury/death, although it did not inhibit N-methyl-D-aspartate (NMDA)-induced excitotoxicity. (-)-Linalool significantly reduced intracellular oxidative stress during OGD/R-induced injury, as well as scavenging peroxyl radicals (Trolox equivalents or TE = 3.8). This anti-oxidant effect was found to correlate with the restoration of OGD/R-induced decreases in the activities of SOD and catalase. In addition, (-)-linalool inhibited microglial migration induced by monocyte-chemoattractant protein-1 (MCP-1), a chemokine released by OGD/R. These findings show that (-)-linalool has neuroprotective effects against OGD/R-induced neuronal injury, which may be due to its anti-oxidant and anti inflammatory activities. Detailed examination of the anti-ischemic mechanisms of (-)-linalool may indicate strategies for the development of drugs to treat cerebral ischemic injury. PMID- 26832327 TI - Design and prediction of new acetylcholinesterase inhibitor via quantitative structure activity relationship of huprines derivatives. AB - Acetylcholinesterase (AChE) is an important enzyme in the pathogenesis of Alzheimer's disease (AD). Comparative quantitative structure-activity relationship (QSAR) analyses on some huprines inhibitors against AChE were carried out using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA), and hologram QSAR (HQSAR) methods. Three highly predictive QSAR models were constructed successfully based on the training set. The CoMFA, CoMSIA, and HQSAR models have values of r (2) = 0.988, q (2) = 0.757, ONC = 6; r (2) = 0.966, q (2) = 0.645, ONC = 5; and r (2) = 0.957, q (2) = 0.736, ONC = 6. The predictabilities were validated using an external test sets, and the predictive r (2) values obtained by the three models were 0.984, 0.973, and 0.783, respectively. The analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the AChE to further understand the vital interactions between huprines and the protease. On the basis of the QSAR study, 14 new potent molecules have been designed and six of them are predicted to be more active than the best active compound 24 described in the literature. The final QSAR models could be helpful in design and development of novel active AChE inhibitors. PMID- 26832328 TI - A Case of Syndromic X-linked Ichthyosis with Leri-Weill Dyschondrosteosis. PMID- 26832329 TI - ZnCr2O4 Nanoparticles: Facile Synthesis, Characterization, and Photocatalytic Properties. AB - In this work, zinc chromite (ZnCr2O4) nanostructures have been synthesized through co-precipitation method. The effect of various parameters such as alkaline agent, pH value, and capping agent type was investigated on purity, particle size and morphology of samples. It was found that particle size and morphology of the products could be greatly influenced via these parameters. The synthesized products were characterized by field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), fourier transform infrared (FT-IR) spectra, X-ray energy dispersive spectroscopy (EDS), photoluminescence (PL) spectroscopy, diffuse reflectance spectroscopy (DRS) and vibrating sample magnetometry (VSM). The superhydrophilicity of the calcined oxides was investigated by wetting experiments and a sessile drop technique which carried out at room temperature in air to determine the surface and interfacial interactions. Furthermore, the photocatalytic activity of ZnCr2O4 nanoparticles was confirmed by degradation of anionic dyes such as Eosin-Y and phenol red under UV light irradiation. The obtained ZnCr2O4 nanoparticles exhibit a paramagnetic behavior although bulk ZnCr2O4 is antiferromagnetic, this change in magnetic property can be ascribed to finite size effects. PMID- 26832330 TI - Effects of differences in age and body height on normal values of central motor conduction time determined by F-waves. AB - OBJECTIVES: To investigate the effect on central motor conduction time (CMCT) based on the relationship between age and height in normal subjects. DESIGN: Retrospective study. METHODS: One hundred and ninety nine normal subjects (107 men and 92 women; mean age 39.0 +/- 16.4 years; mean height 164.5 +/- 8.8 cm) participated in the study. The approximate ages of subjects were as follows: 82 (20-29 years old), 32 (30-39 years old), 32 (40-49 years old), 28 (50-59 years old), and 25 (?60 years old). The heights of 9, 49, 79, 53, and 9 subjects were <150 cm, 150-160 cm, 160-170 cm, 170-180 cm, and >180 cm, respectively. CMCT- abductor digiti minimi (ADM) and abductor hallucis (AH) were calculated by subtracting the peripheral motor conduction time (PMCT) from the onset latency of motor evoked potentials (MEPs) evoked by transcranial magnetic stimulation. PMCT was calculated from the latencies of the compound muscle action potentials (CMAPs) and F-waves as follows: (latency of CMAPs + latency of F-waves -1)/2. OUTCOME MEASURES: CMCT-ADM and CMCT-AH. RESULTS: The normative values were 5.2 +/ 0.8 ms and 11.8 +/- 1.3 ms for CMCT-ADM and CMCT-AH, respectively. CMCT-ADM was not significantly correlated with age (P = 0.196) and body height (P = 0.158). CMCT-AH had significantly positive, linear correlations with age and body height (CMCT-AH = 0.014 * age + 10.971, P = 0.011, R = 0.179 and CMCT-AH = 0.026 * body height + 7.158, P = 0.010, R = 0.182). CONCLUSIONS: We suggest normative values of 3.2-7.2 ms in CMCT-ADM for subjects exerting slight effort on ADM regardless age and body height. CMCT-AH had significantly positive, linear correlations with age and body height. PMID- 26832331 TI - HDAC3-Dependent Epigenetic Pathway Controls Lung Alveolar Epithelial Cell Remodeling and Spreading via miR-17-92 and TGF-beta Signaling Regulation. AB - The terminal stages of pulmonary development, called sacculation and alveologenesis, involve both differentiation of distal lung endoderm progenitors and extensive cellular remodeling of the resultant epithelial lineages. These processes are coupled with dramatic expansion of distal airspace and surface area. Despite the importance of these late developmental processes and their relation to neonatal respiratory diseases, little is understood about the molecular and cellular pathways critical for their successful completion. We show that a histone deacetylase 3 (Hdac3)-mediated epigenetic pathway is critical for the proper remodeling and expansion of the distal lung saccules into primitive alveoli. Loss of Hdac3 in the developing lung epithelium leads to a reduction of alveolar type 1 cell spreading and a disruption of lung sacculation. Hdac3 represses miR-17-92 expression, a microRNA cluster that regulates transforming growth factor beta (TGF-beta) signaling. De-repression of miR-17-92 in Hdac3 deficient lung epithelium results in decreased TGF-beta signaling activity. Importantly, inhibition of TGF-beta signaling and overexpression of miR-17-92 can phenocopy the defects observed in Hdac3 null lungs. Conversely, loss of miR-17-92 expression rescues many of the defects caused by loss of Hdac3 in the lung. These studies reveal an intricate epigenetic pathway where Hdac3 is required to repress miR-17-92 expression to allow for proper TGF-beta signaling during lung sacculation. PMID- 26832332 TI - The 57th amino acid conveys the differential subcellular localization of human immunodeficiency virus-1 Tat derived from subtype B and C. AB - The multifunctional transactivator Tat protein is an essentially regulatory protein for HIV-1 replication and it plays a role in pathogenesis of HIV-1 infection. At present, numerous experimental studies about HIV-1 Tat focus on subtype B, very few has been under study of subtype C-Tat. In view of the amino acid variation of the clade-specific Tat proteins, we hypothesized that the amino acid difference contributed to differential function of Tat proteins. In the present study, we documented that subtype B NL4-3 Tat and subtype C isolate HIV1084i Tat from pediatric patient in Zambia exhibited distinct nuclear localization by over-expressing fusion protein Tat-EGFP. Interestingly, 1084i Tat showed uniform nuclear distribution, whereas NL4-3 Tat primarily localized in nucleolus. The 57th amino acid, highly conserved between B-Tat (arginine) and C Tat (serine), is located in the basic domain of Tat, and played an important role in this subcellular localization. Meanwhile, we found that substitution of arginine to serine at the site 57 decreases Tat transactivation of the HIV-1 LTR promoter. PMID- 26832333 TI - Effects of topical adrenergic agents on prostaglandin E2-induced aqueous flare and intraocular pressure elevation in pigmented rabbits. AB - PURPOSE: To evaluate the effects of signals through adrenergic receptors on the changes in the aqueous flare and intraocular pressure (IOP) induced by topical prostaglandin E2 (PGE2) in pigmented rabbits. METHODS: Adrenergic agents were applied topically to pigmented Dutch rabbits, and PGE2 was then applied to induce an increase in the aqueous flare and IOP. The degree of aqueous flare was measured with a laser flare meter, and the IOP was measured with a rebound tonometer. Measurements were made every 30 min after the PGE2 had been applied for 2 h and at 4.0 and 4.5 h. Repeated measure analysis of variance and Dunnett's post hoc tests were used for the statistical analyses. RESULTS: The topical application of PGE-2 increased the aqueous flare for more than 4.5 h. The topical instillation of 1.0 % apraclonidine significantly inhibited the increase in the PGE2-induced aqueous flare by 75.1 %, of 0.1 % brimonidine by 57.2 %, of 0.04 % dipivefrin by 57.4 %, and a combination of 0.1 % brimonidine and 5 % phenylephrine by 78.9 %. Topical 5.0 % phenylephrine and 0.05 % isoproterenol had little effect on the aqueous flare elevation induced by PGE2. The IOP increased 0.5 h after the topical application of PGE-2. Topical 1.0 % apraclonidine, 0.1 % brimonidine, 0.1 % dipivefrin, and the combination of 0.1 % brimonidine and 5.0 % phenylephrine significantly inhibited the PGE2-induced IOP elevation. However, topical 5.0 % phenylephrine and 0.05 % isoproterenol did not significantly inhibit the IOP elevation caused by PGE2. CONCLUSIONS: Signaling by the alpha2 receptor inhibits both the PGE2-induced flare and IOP elevation caused by topical PGE2 application. PMID- 26832334 TI - Religion and Happiness: A Study Among University Students in Turkey. AB - This study tests the hypothesis that higher levels of positive religious affect are associated with higher levels of personal happiness among a sample of 348 students studying at a state university in Turkey who completed the Ok Religious Attitude Scale (Islam), the Oxford Happiness Inventory, and the short-form Eysenck Personality Questionnaire Revised. The data reported a small but statistically significant association between religiosity and happiness after taking sex and individual differences in personality into account. PMID- 26832335 TI - Incorporating Spirituality in Primary Care. AB - Addressing cultural competency in health care involves recognizing the diverse characteristics of the patient population and understanding how they impact patient care. Spirituality is an aspect of cultural identity that has become increasingly recognized for its potential to impact health behaviors and healthcare decision-making. We consider the complex relationship between spirituality and health, exploring the role of spirituality in primary care, and consider the inclusion of spirituality in existing models of health promotion. We discuss the feasibility of incorporating spirituality into clinical practice, offering suggestions for physicians. PMID- 26832337 TI - A joint model for longitudinal and time-to-event data to better assess the specific role of donor and recipient factors on long-term kidney transplantation outcomes. AB - In renal transplantation, serum creatinine (SCr) is the main biomarker routinely measured to assess patient's health, with chronic increases being strongly associated with long-term graft failure risk (death with a functioning graft or return to dialysis). Joint modeling may be useful to identify the specific role of risk factors on chronic evolution of kidney transplant recipients: some can be related to the SCr evolution, finally leading to graft failure, whereas others can be associated with graft failure without any modification of SCr. Sample data for 2749 patients transplanted between 2000 and 2013 with a functioning kidney at 1-year post-transplantation were obtained from the DIVAT cohort. A shared random effect joint model for longitudinal SCr values and time to graft failure was performed. We show that graft failure risk depended on both the current value and slope of the SCr. Deceased donor graft patient seemed to have a higher SCr increase, similar to patient with diabetes history, while no significant association of these two features with graft failure risk was found. Patient with a second graft was at higher risk of graft failure, independent of changes in SCr values. Anti-HLA immunization was associated with both processes simultaneously. Joint models for repeated and time-to-event data bring new opportunities to improve the epidemiological knowledge of chronic diseases. For instance in renal transplantation, several features should receive additional attention as we demonstrated their correlation with graft failure risk was independent of the SCr evolution. PMID- 26832338 TI - Oral acetate supplementation attenuates N-methyl D-aspartate receptor hypofunction-induced behavioral phenotypes accompanied by restoration of acetyl histone homeostasis. AB - RATIONALE: Aberrations in cellular acetate-utilization processes leading to global histone hypoacetylation have been implicated in the etiology of neuropsychiatric disorders like schizophrenia. OBJECTIVES: Here, we investigated the role of acetate supplementation in the form of glyceryl triacetate (GTA) for the ability to restore the N-methyl D-aspartate (NMDA) receptor-induced histone hypoacetylation and to ameliorate associated behavioral phenotypes in mice. RESULTS: Taking cues from the studies in SH-SY5Y cells, we monitored acetylation status of specific lysine residues of histones H3 and H4 (H3K9 and H4K8) to determine the impact of oral GTA supplementation in vivo. Mice treated chronically with MK-801 (10 days; 0.15 mg/kg daily) induced hypoacetylation of H3K9 and H4K8 in the hippocampus. Daily oral supplementation of GTA (2.9 g/kg) was able to prevent this MK801-induced hypoacetylation significantly. Though MK 801-stimulated decreases in acetyl-H3K9 and acetyl-H4K8 were found to be associated with ERK1/2 activation, GTA seemed to act independent of this pathway. Simultaneously, GTA administration was able to attenuate the chronic MK-801 induced cognitive behavior phenotypes in elevated plus maze and novel object recognition tests. Not only MK-801, GTA also demonstrated protective effects against behavioral phenotypes generated by another NMDA receptor antagonist, ketamine. Acute (single injection) ketamine-mediated hyperactivity phenotype and chronic (10 days treatment) ketamine-induced phenotype of exaggerated immobility in forced swim test were ameliorated by GTA. CONCLUSION: The signature behavioral phenotypes induced by acute and chronic regimen of NMDA receptor antagonists seemed to be attenuated by GTA. This study thus provides a therapeutic paradigm of using dietary acetate supplement in psychiatric disorders. PMID- 26832339 TI - The effect of a dopamine antagonist on conditioning of sexual arousal in women. AB - RATIONALE: Dopamine (DA) plays a key role in reward-seeking behaviours. Accumulating evidence from animal and human studies suggests that human sexual reward learning may also depend on DA transmission. However, research on the role of DA in human sexual reward learning is completely lacking. OBJECTIVES: To investigate whether DA antagonism attenuates classical conditioning of sexual response in humans. METHODS: Healthy women were randomly allocated to one of two treatment conditions: haloperidol (n = 29) or placebo (n = 29). A differential conditioning paradigm was applied with genital vibrostimulation as unconditional stimulus (US) and neutral pictures as conditional stimuli (CSs). Genital arousal was assessed, and ratings of affective value and subjective sexual arousal were obtained. RESULTS: Haloperidol administration affected unconditional genital responding. However, no significant effects of medication were found for conditioned responding. CONCLUSIONS: No firm conclusions can be drawn about whether female sexual reward learning implicates DA transmission since the results do not lend themselves to unambiguous interpretation. PMID- 26832340 TI - Association of depression with pre-diabetes, undiagnosed diabetes, and previously diagnosed diabetes: a meta-analysis. AB - We performed a meta-analysis to analyze the associations of depression with pre diabetes (PreDM), undiagnosed diabetes (UDM), and previously diagnosed diabetes (PDM), and whether the association was affected by important study characteristics. We searched relevant articles published in PubMed and EMBASE up to August, 2015. Studies reporting cross-sectional associations of depression with PreDM, UDM, or PDM compared with normal glucose metabolism (NGM) were included. Odds ratios (ORs) were pooled with random-effect and fixed-effect models. Subgroup analyses by sex, study mean age, different degrees of adjustment, publication year, quality score, and depression assessment scales were also performed. Twenty studies were eligible and included in current analysis. Summary estimates showed that compared with NGM individuals, prevalence of depression was moderately increased in PreDM (random-effect odds ratio (OR) 1.11, 95 % confidence interval (CI) 1.03-1.19) and UDM (OR 1.27, 95 % CI 1.02 1.59), and markedly increased in PDM (OR 1.80, 95 % CI 1.40-2.31). Subgroup analyses showed that the positive association remained only among studies with mean age <60 years old but not among those with mean age >=60 years old. Summary estimates of ORs with cardiovascular disease adjustment substantially attenuated the association. Our findings suggested that risk of prevalent depression was gradually increased with the deterioration of glucose metabolism among younger age groups but not among older age groups. Comorbid cardiovascular diseases might be an important intermediate factor underlying the association between depression and diabetes. PMID- 26832341 TI - Glucagon-like peptide-2 treatment improves glucose dysmetabolism in mice fed a high-fat diet. AB - Previous studies suggested that endogenous glucagon-like peptide 2 (GLP-2) is dispensable for the regulation of glucose homeostasis under normal conditions, while it can play a beneficial role in obesity conditions. The purpose of the present study was to investigate whether chronic treatment with Gly2-GLP-2, a stable analogue of GLP-2, can have an impact on glycaemic and lipid control in mice fed a high-fat diet (HFD), an animal model of human obesity and insulin resistance. HFD mice were treated once a day with Gly2-GLP-2 for 4 weeks. Body weight, food intake, fasting glucose, intraperitoneal glucose tolerance, insulin induced glucose clearance, glucose-stimulated insulin secretion, beta-cell mass, plasma lipid metabolic profile, and lipid deposition in the liver were examined. In untreated HFD mice, fasting glucose levels, glucose tolerance, glucose stimulated plasma insulin and sensibility to exogenous insulin were deteriorating with time and beta-cell mass increased. In Gly2-GLP-2-treated mice, we found significant increase in glucose tolerance and exogenous insulin sensitivity, reduction in glucose-stimulated plasma insulin and in the increase in beta-cell mass in comparison with pair-aged HFD untreated animals. The chronic treatment with the peptide was not associated with remarkable improvements of dyslipidemia and it did not prevent liver fat accumulation and the presence of microvesicular steatosis. In conclusion, the results of the present study suggest, for the first time, that Gly2-GLP-2 may produce glucose metabolic benefits in mice with diet induced obesity. The mechanisms underlying the beneficial impact of GLP-2 on glucose metabolism remain to be established. PMID- 26832342 TI - Alleviation of high-fat diet-induced atherosclerosis and glucose intolerance by a novel GLP-1 fusion protein in ApoE(-/-) mice. AB - We have previously constructed an engineered anti-diabetic fusion protein using glucagon-like peptide-1 and the globular domain of adiponectin. Herein, we evaluated the therapeutic effects of this fusion protein (GAD) on high-fat diet (HFD)-fed ApoE(-/-) mice. The lipid-lowering effect of GAD was determined in C57BL/6 mice using a lipid tolerance test. The effects of GAD on HFD-induced glucose intolerance, atherosclerosis, and hepatic steatosis were evaluated in HFD fed ApoE(-/-) mice using glucose tolerance test, histological examinations and real-time quantitative PCR. The anti-inflammation activity of GAD was assessed in vitro on macrophages. GAD improved lipid metabolism in C57BL/6 mice. GAD treatment alleviated glucose intolerance, reduced blood lipid level, and attenuated atherosclerotic lesion in HFD-fed ApoE(-/-) mice, which was associated with a repressed macrophage infiltration in the vessel wall. GAD treatment also blocked hepatic macrophage infiltration and prevented hepatic inflammation. GAD suppressed lipopolysaccharide-triggered inflammation responses on macrophages, which can be abolished by H89, an inhibitor of protein kinase A. These findings demonstrate that GAD is able to generate a variety of metabolic benefits in HFD fed ApoE(-/-) mice and indicate that this engineered fusion protein is a promising lead structure for anti-atherosclerosis drug discovery. PMID- 26832345 TI - John H. Beynon (1923-2015). PMID- 26832343 TI - Elevated circulating levels of betatrophin are associated with polycystic ovary syndrome. AB - Betatrophin is a newly identified hormone determined to be a potent inducer of pancreatic beta cell proliferation in response to insulin resistance in mice. Polycystic ovary syndrome (PCOS) is an inflammatory-based metabolic disease associated with insulin resistance. However, no evidence is available indicating whether betatrophin is involved in women with PCOS. The objective of this study was to ascertain whether betatrophin levels are altered in women with PCOS. This study was conducted in secondary referral center. This cross-sectional study included 164 women with PCOS and 164 age- and BMI-matched female controls. Circulating betatrophin levels were measured using ELISA. Metabolic and hormonal parameters were also determined. Circulating betatrophin levels were significantly elevated in women with PCOS compared with controls (367.09 +/- 55.78 vs. 295.65 +/- 48.97 pg/ml, P < 0.001). Betatrophin levels were positively correlated with insulin resistance marker homeostasis model assessment of insulin resistance (HOMA-IR), free-testosterone, high-sensitivity C-reactive protein (hs CRP), atherogenic lipid profiles, and BMI in PCOS. Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 2.51 for patients in the highest quartile of betatrophin compared with those in the lowest quartile (95 % CI 1.31-4.81, P = 0.006). Multivariate regression analyses showed that HOMA IR, hs-CRP, and free-testosterone were independent factors influencing serum betatrophin levels. Betatrophin levels were increased in women with PCOS and were associated with insulin resistance, hs-CRP, and free-testosterone in these patients. Elevated betatrophin levels were found to increase the odds of having PCOS. Further research is needed to elucidate the physiologic and pathologic significance of our findings. PMID- 26832346 TI - Peter J. Todd (1949-2015). PMID- 26832344 TI - Association of SLC30A8 gene polymorphism with type 2 diabetes, evidence from 46 studies: a meta-analysis. AB - The solute carrier family 30 member 8 (SLC30A8) gene may be involved in the development of type 2 diabetes mellitus (T2DM) through disrupting beta-cell function. The aim of this study was to assess the association between SLC30A8 rs13266634 polymorphism and susceptibility to T2DM. We searched all reports regarding the association between SLC30A8 rs13266634 polymorphism and T2DM risk through Pubmed, Embase, and the Cochrane Library for English language reports and Chongqing VIP database, Wanfang data, CBMDisc, and CNKI for Chinese language studies. Allelic and genotype comparisons between cases and controls were evaluated, and odds ratios with 95 % confidence intervals were used to assess the strength of their association. A random effects model was selected. Publication bias was estimated using Begg's test. Forty-six studies were included in the analysis with a total of 71,890 cases and 96,753 controls. This meta-analysis suggests that SLC30A8 (rs13266634) polymorphism was associated with T2DM risk. Although previous meta-analyses have shown that this association was only found in Asian and European groups, and not in African populations, our analysis revealed the deleterious effect of SLC30A8 rs13266634 on T2DM in an African population when stratified by ethnicity under additive model even with a small number of studies. PMID- 26832347 TI - Fragmentation Patterns and Mechanisms of Singly and Doubly Protonated Peptoids Studied by Collision Induced Dissociation. AB - Peptoids are peptide-mimicking oligomers consisting of N-alkylated glycine units. The fragmentation patterns for six singly and doubly protonated model peptoids were studied via collision-induced dissociation tandem mass spectrometry. The experiments were carried out on a triple quadrupole mass spectrometer with an electrospray ionization source. Both singly and doubly protonated peptoids were found to fragment mainly at the backbone amide bonds to produce peptoid B-type N terminal fragment ions and Y-type C-terminal fragment ions. However, the relative abundances of B- versus Y-ions were significantly different. The singly protonated peptoids fragmented by producing highly abundant Y-ions and lesser abundant B-ions. The Y-ion formation mechanism was studied through calculating the energetics of truncated peptoid fragment ions using density functional theory and by controlled experiments. The results indicated that Y-ions were likely formed by transferring a proton from the C-H bond of the N-terminal fragments to the secondary amine of the C-terminal fragments. This proton transfer is energetically favored, and is in accord with the observation of abundant Y-ions. The calculations also indicated that doubly protonated peptoids would fragment at an amide bond close to the N-terminus to yield a high abundance of low-mass B ions and high-mass Y-ions. The results of this study provide further understanding of the mechanisms of peptoid fragmentation and, therefore, are a valuable guide for de novo sequencing of peptoid libraries synthesized via combinatorial chemistry. Graphical Abstract ?. PMID- 26832348 TI - Orexinergic system in the locus coeruleus modulates the CO2 ventilatory response. AB - The orexins are hypothalamic neuropeptides involved in an array of functions such as regulation of sleep/wake states and chemoreception to CO2/pH. The locus coeruleus (LC) is a chemosensitive site and expresses an extensive population of orexin receptor 1 (OX1R). We tested the hypothesis that OX1Rs located in the LC participate in the ventilatory response to hypercapnia in a vigilance state and diurnal cycle-dependent manner. For this, we performed unilateral injections of SB-334867 (OX1R antagonist, 5 mM) into the LC of male Wistar rats and evaluated the ventilatory response to 7 % CO2 during wakefulness and sleep in the dark and light phases of the diurnal cycle. Hypercapnia induced an increase in ventilation (V E) in all groups compared to normocapnic values. However, during the dark phase, but not in the light phase, SB-334867 injection promoted an attenuation of the hypercapnic chemoreflex during wakefulness (V E: vehicle, 1502.6 +/- 100 mL kg(-1) min(-1) vs SB-334867, 1200.3 +/- 70.0 mL kg(-1) min(-1)) but not during sleep (V E: vehicle, 1383.0 +/- 113.9 vs SB-334687, 1287.6 +/- 92.1 mL kg(-1) min(-1)), due to changes in tidal volume (V T). We suggest that projections of orexin-containing neurons to the LC contribute, via OX1Rs, to the hypercapnic chemoreflex during wakefulness in the dark phase. PMID- 26832349 TI - Transvaginal specimen removal in minimally invasive surgery. AB - The demand for urological surgical treatment associated with better cosmesis, lower morbidity rates and shorter hospitalization constantly grows. The transvaginal route has been proposed in an attempt to avoid long abdominal incisions for the removal of the large laparoscopic specimens. Moreover, the transvaginal NOTES approach represents a promising evolution of laparoscopic surgery to a more "minimally invasive" alternative. The current review summarizes the available experience in the literature in transvaginal conventional laparoscopy and NOTES in urology, gynecology and general surgery. The clinical outcome is presented. The most important issues associated with the transvaginal approach are the complications and the postoperative sexual function. These issues are presented. PMID- 26832350 TI - Comparison of pre-treatment MSKCC and IMDC prognostic risk models in patients with synchronous metastatic renal cell carcinoma treated in the era of targeted therapy. AB - PURPOSE: To compare prognostic performance of MSKCC and IMDC risk models in patients with synchronous mRCC. METHODS: Retrospective analysis of pre therapeutic MSKCC and IMDC prognostic factors and outcomes in patients with synchronous mRCC treated at a single institute in the targeted therapy era was performed. Cytoreductive nephrectomy (CN) was performed in patients with WHO performance 0-1 and limited metastasis. RESULTS: Of 190 patients, only 2 had favourable risk. Overall, 141 patients received targeted therapy and 97 underwent CN. By MSKCC score, 143 (76.1 %) patients were intermediate risk (median OS 16 months) but only 97 (51.9 %) by IMDC (median OS 23 months). Conversely, 46 of the MSKCC intermediate-risk patients (31.2 %) were IMDC poor risk. Only poor risk by MSKCC and >=4 IMDC factors had similar poor outcome (median OS 5 months and OS 2 years of 4.1 % and 10.4 %, respectively). Following CN, baseline elevated platelets and neutrophils decreased to normal in 61.5 and 75 %, respectively. This suggests that the primary tumour may influence baseline counts resulting in more IMDC poor risk. In both models, CN status was associated with better OS. CONCLUSION: Patients with synchronous mRCC and poor risk by MSKCC or >=4 IMDC factors have a short survival expectancy, and CN may not be the primary objective in this population. Conversely, with either MSKCC or IMDC intermediate risk the probability to survive 2 years is 38.6-45.7 %, which suggests that a subgroup of patients live long enough to derive a potential benefit of CN. PMID- 26832352 TI - Dante Alighieri: poet of the syncope. PMID- 26832351 TI - Carbohydrate-antigen-125 levels predict hospital stay duration and adverse events at long-term follow-up in Takotsubo cardiomyopathy. AB - The aim of this study is to evaluate the possible role of carbohydrate antigen(CA)-125 as prognostic marker at short- and long-term follow-up, in subjects with Takotsubo cardiomyopathy (TTC). Sixty-three consecutive subjects with TTC were enrolled in the study and followed for a median 139 days. Circulating levels of CA-125, NT-proBNP, and left ventricular ejection fraction (LVEF) were evaluated at admission. Duration of hospital stay, incidence of death, re-hospitalization and recurrence of TTC during follow-up were recorded. The mean hospital stay was 8.3 days, adverse events occurred during follow up in 17 % of cases. CA-125 levels at admission are inversely related to LVEF (r -0.30, p < 0.05) and directly related to hospital stay (r 0.29, p < 0.05). CA-125 levels at admission are higher in subjects with adverse events at follow-up (88.9 +/- 200.0 vs 20.9 +/- 30.0 U/mL, p < 0.05). Rates of incidence of adverse events are proportionally increased with CA-125 tertiles (0, 6, 11 % respectively, p for trend <0.01), at survival analysis (Log Rank p < 0.05) and after correction for age, gender, LVEF and NT-proBNP levels in multivariable Cox analysis (p < 0.05). CA-125 levels <10 U/ml are predictors of adverse events at follow up with 91 % sensitivity, 52 % specificity, 29 % positive predictive power, and 96 % negative predictive power. Increased CA-125 admission levels are associated with a longer hospital stay, a lower LVEF, and a higher risk of adverse events during follow up. CA-125 might be useful for early risk stratification of subjects with TTC. PMID- 26832353 TI - Study on the priority of coronary arteriography or therapeutic hypothermia after return of spontaneous circulation in patients with out-of-hospital cardiac arrest: results from the SOS-KANTO 2012 study. AB - Many emergency physicians struggle with the clinical question of whether to perform therapeutic hypothermia (TH) or coronary angiography (CAG) first after return of spontaneous circulation (ROSC) in patients with out-of-hospital cardiac arrest (OHCA). We analyzed the results of the SOS-KANTO 2012 study, which is a prospective, multicenter (67 emergency hospitals), observational study about OHCA conducted between January 2012 and March 2013 (n = 16,452). We compared two groups: the group in which TH was first performed (TH group), and the group in which CAG was performed first (CAG group) within 24 h after arrival. Two hundred and twenty-one patients were treated TH and CAG (TH group, 76 patients; CAG group, 145 patients). In addition, we selected patients who underwent coronary treatment. 164 patients underwent coronary treatment after CAG (TH group, 52 patients; CAG group, 112 patients). In patients in whom TH and CAG and coronary artery treatment were done, 42 patients (55.3 %) in the TH group and 86 patients (59.3 %) in the CAG group survived at 90 days. The cerebral performance category (CPC) 1 and 2 were 26.3 % (20 patients) in TH group, and 31.0 % (45 patients) in CAG group. In patients in whom TH and CAG with coronary artery treatment were performed, 29 patients (55.8 %) in the TH group and 64 patients (57.1 %) in the CAG group survived at 90 days. The rates of CPC 1 and 2 were 26.9 % (14 patients) in TH group, and 23.2 % (26 patients) in CAG group. There was no significant difference in 90-day survival between the two groups although it tended to be better in the CAG group than in the TH group. Whether TH or CAG was performed first did not affect the 90-day survival and 30-day neurological situation among patients with ROSC after OHCA. PMID- 26832354 TI - Formal support for informal caregivers to older persons with dementia through the course of the disease: an exploratory, cross-sectional study. AB - BACKGROUND: In European countries, knowledge about availability and utilization of support for informal caregivers caring for older persons (>=65 years) with dementia (PwD) is lacking. To be able to evaluate and develop the dementia support system for informal caregivers to PwD, a survey of European support systems and professionals involved is needed. The aim of this study was to explore support for informal caregivers to PwD in European countries. We investigated the availability and utilization of support in each of the participating countries, and the professional care providers involved, through the dementia disease. METHODS: A mapping system was used in 2010-2011 to gather information about estimations of availability, utilization, and professional providers of support to informal caregivers caring for PwD. Data collected was representing each country as a whole. RESULTS: There was high availability of counselling, caregiver support, and education from the diagnosis to the intermediate stage, with a decrease in the late to end of life stage. Utilization was low, although there was a small increase in the intermediate stage. Day care and respite care were highly available in the diagnosis to the intermediate stage, with a decrease in the late to end of life stage, but both types of care were utilized by few or no caregivers through any of the disease stages. Professionals specialized in dementia (Bachelor to Master's degree) provided counselling and education, whereas caregiver support for informal caregivers and day care, respite care, and respite care at home were provided by professionals with education ranging from upper secondary schooling to a Master's degree. CONCLUSIONS: Counselling, caregiver support, and education were highly available in European countries from diagnosis to the intermediate stage of the dementia disease, decreasing in the late/end of life stages but were rarely utilized. Countries with care systems based on national guidelines for dementia care seem to be more aware of the importance of professionals specialized in dementia care when providing support to informal caregivers. Mapping the systems of support for informal caregivers of PwD is a valuable tool for evaluating existing systems, internationally, nationally and locally for policy making. PMID- 26832355 TI - Sensation seeking as a potential screening tool for suicidality in adolescence. AB - BACKGROUND: Although suicide could be an adverse health problem related to sensation seeking, this relationship has not been rigorously evaluated. The purpose of this study was to evaluate the relationship between sensation seeking and suicidality (suicidal ideation and plan) among adolescents and to test the influence of depressive symptom on this relationship. METHODS: We surveyed 2,017 adolescents in seven middle and high schools located in urban and rural areas in 2012. A self-report questionnaire included items about demographic characteristics, sensation seeking, depressive symptom, and suicide plans. We evaluated the influence of sensation seeking on suicide plan using multiple logistic regression and causal mediation analysis. RESULTS: Sensation seeking was related to suicide ideation and plan. Sensation seeking was associated with a 13 % greater likelihood of a suicide plan during the past 12 months as the score increased by 1. After controlling for depressive symptom, the effect of sensation seeking was reduced, but still significantly increased the risk (adjusted odds ratio: 1.10; 95 % CI: 1.04-1.16). When depressive symptom was included as a potential mediator, depressive symptom exerted an indirect effect on suicide planning that constituted 37 % of the total effect of sensation seeking. There was no significant interaction between sensation seeking and either demographic variables or depressive symptom. CONCLUSIONS: Sensation seeking can contribute to developing a suicide plan directly and indirectly via depressive symptom. Sensation seeking could be used to identify high-risk adolescents and provide proper interventions. PMID- 26832356 TI - Traceability, reproducibility and clinical evaluation of Sansure Realtime HCV RNA assay. AB - BACKGROUND: Accurate quantitative detection of hepatitis C virus (HCV) RNA is critical for diagnosis of acute or chronic HCV infection, and for follow-up of virologic response during HCV targeted therapy. In the present study, traceability and reproducibility of a novel China-certified domestic Sansure HCV RNA diagnostic assay (Sansure, Changsha, Hunan, China) was evaluated and the clinical performance of this assay was also analyzed. METHODS: Traceability of the Sansure HCV RNA assay to the WHO international standard for HCV (genotype 1a) was detected across multiple centers. Reproducibility, accuracy (the differences of observed average concentrations and expected concentrations) and precision were assessed using series dilutions of World HCV RNA performance panel WWHV303 02 (HCV-1b), WWHV303-04(HCV-2a), WWHV303-11(HCV-3a) and WWHV303-19 (HCV-6a). In addition, both Sansure HCV RNA and CAP/CTM HCV (Roche, Branchburg, NJ, USA) assays were used to detect HCV RNA in 346 EDTA anti-coagulated plasma samples from previous HCV-infected patients, during and after antiviral therapy. RESULTS: The Sansure assay showed good traceability by agreeing with the HCV-1a WHO standard across all five concentrations tested (25, 50, 100, 1000, 10,000 IU/ml). The differences between observed average concentrations and expected concentrations were all within 0.2 log10 IU/ml. HCV WWHV303 standards across 4 HCV genotypes (1b, 2a, 3a and 6a) were used for evaluation of reproducibility and the accuracy of the test were all within 0.2 log10 IU/ml. The inter-assay variations across the above 4 HCV genotypes were all less than 0.03 on each evaluated concentration, indicating good precision of Sansure HCV RNA assay. In clinical practice, concordant results were determined in 99.42% (344/346) samples (215 positive and 129 negative samples). Two specimens with negative HCV RNA results by Sansure assay were detected positive by CAP/CTM HCV test. Correlation analysis indicated a significantly positive correlation in detected HCV RNA concentrations (r = 0.9439, P < 0.0001). HCV RNA levels in 95.35% (205/215) specimens were within mean difference +/- 1.96 SD as tested by both assays. CONCLUSIONS: With the advantages of traceability, reproducibility and lower price, Sansure HCV RNA assay represented an alternative option for HCV RNA detection in hospital and medical institution in China. PMID- 26832357 TI - Metabolic Basis of Polycystic Ovarian Syndrome; Indications for Biochemical Screening. AB - BACKGROUND: Polycystic ovary syndrome (PCOS) is a heterogeneous condition with wide range of phenotype the cause of this disorder is unknown, however, increased ovarian androgen production including increased theca cell responsiveness to gonadotropin stimulation, increased pituitary secretion of luteinizing hormone, and hyperinsulinemia have been suggested. Some known risk factors are ethnicity and environmental factors including lifestyle and bodyweight. METHOD: Relevant English language studies from January 1995 to September 2015 were identified, reviewed, synthesized and discussed extensively. RESULT: various forms of PCOS, and the underlying mechanisms; and highlights biochemical, morphological and metabolic hallmarks of PCOS, including trends and emerging phenotypes; and presents a simplified synthesis that integrates current understanding of biochemical and metabolic endocrinology of PCOS are summarized. As no generally accepted criteria exist for its diagnosis, some existing diagnostic criteria that cut across different geographical regions are also highlighted. CONCLUSION: Indeed, emerging evidence points that the severity of menstrual problems could serve as a predictor of the like-hood of insulin resistance in women of reproductive age, suggesting the need for routine metabolic screening and early intervention in PCOS. PMID- 26832358 TI - Asfotase Alfa in Perinatal/Infantile-Onset and Juvenile-Onset Hypophosphatasia: A Guide to Its Use in the USA. AB - Subcutaneous asfotase alfa (StrensiqTM), a first-in-class bone-targeted human recombinant tissue-nonspecific alkaline phosphatase (TNSALP) replacement therapy, is approved in the USA for the treatment of patients with perinatal/infantile- or juvenile-onset hypophosphatasia (HPP). In clinical trials, asfotase alfa was an effective and generally well tolerated treatment for perinatal/infantile- and juvenile onset-HPP through at least 3 and 5 years' treatment, respectively. Relative to untreated age-matched, juvenile-onset-HPP historical control cohorts, survival and ventilation-free survival were significantly prolonged in asfotase alfa-treated patients, consequent to preceding improvements in bone mineralization. PMID- 26832359 TI - Cancer survival in New South Wales, Australia: socioeconomic disparities remain despite overall improvements. AB - BACKGROUND: Disparities in cancer survival by socioeconomic status have been reported previously in Australia. We investigated whether those disparities have changed over time. METHODS: We used population-based cancer registry data for 377,493 patients diagnosed with one of 10 major cancers in New South Wales (NSW), Australia. Patients were assigned to an area-based measure of socioeconomic status. Five-year relative survival was estimated for each socioeconomic quintile in each 'at risk' period (1996-2000 and 2004-2008) for the 10 individual cancers. Poisson-regression modelling was used to adjust for several prognostic factors. The relative excess risk of death by socioeconomic quintile derived from this modelling was compared over time. RESULTS: Although survival increased over time for most individual cancers, Poisson-regression models indicated that socioeconomic disparities continued to exist in the recent period. Significant socioeconomic disparities were observed for stomach, colorectal, liver, lung, breast and prostate cancer in 1996-2000 and remained so for 2004-2008, while significant disparities emerged for cervical and uterus cancer in 2004-2008 (although the interaction between period and socioeconomic status was not significant). About 13.4% of deaths attributable to a diagnosis of cancer could have been postponed if this socioeconomic disparity was eliminated. CONCLUSION: While recent health and social policies in NSW have accompanied an increase in cancer survival overall, they have not been associated with a reduction in socioeconomic inequalities. PMID- 26832360 TI - Does exchange arthroplasty of an infected shoulder prosthesis provide better eradication rate and better functional outcome, compared to a permanent spacer or resection arthroplasty? a systematic review. AB - BACKGROUND: The best surgical modality for treating chronic periprosthetic shoulder infections has not been established, with a lack of randomised comparative studies. This systematic review compares the infection eradication rate and functional outcomes after single- or two-stage shoulder exchange arthroplasty, to permanent spacer implant or resection arthroplasty. METHODS: Full-text papers and those with an abstract in English published from January 2000 to June 2014, identified through international databases, such as EMBASE and PubMed, were reviewed. Those reporting the success rate of infection eradication after a single-stage exchange, two-stage exchange, resection arthroplasty or permanent spacer implant, with a minimum follow-up of 6 months and sample size of 5 patients were included. RESULTS: Eight original articles reporting the results after resection arthroplasty (n = 83), 6 on single-stage exchange (n = 75), 13 on two-stage exchange (n = 142) and 8 papers on permanent spacer (n = 68) were included. The average infection eradication rate was 86.7 % at a mean follow-up of 39.8 months (SD 20.8) after resection arthroplasty, 94.7 % at 46.8 months (SD 17.6) after a single-stage exchange, 90.8 % at 37.9 months (SD 12.8) after two stage exchange, and 95.6 % at 31.0 months (SD 9.8) following a permanent spacer implant. The difference was not statistically significant (p = 0.650). Regarding functional outcome, patients treated with single-stage exchange had statistically significant better postoperative Constant scores (mean 51, SD 13) than patients undergoing a two-stage exchange (mean 44, SD 9), resection arthroplasty (mean 32, SD 7) or a permanent spacer implant (mean 31, SD 9) (p = 0.029). However, when considering studies comparing pre- and post-operative Constant scores, the difference was not statistically significant. CONCLUSION: This systematic review failed to demonstrate a clear difference in infection eradication and functional improvement between all four treatment modalities for established periprosthetic shoulder infection. The relatively low number of patients and the methodological limitations of the studies available point out the need for well designed multi center trials to further assess the best treatment option of peri-prosthetic shoulder infection. PMID- 26832361 TI - Diagnosis of diabetes insipidus observed in Swiss Duroc boars. AB - BACKGROUND: Diabetes insipidus (DI) is a rare disease in humans and animals, which is caused by the lack of production, malfunction or dysfunction of the distal nephron to the antidiuretic effect of the antidiuretic hormone (ADH). Diagnosis requires a thorough medical history, clinical examination and further laboratory confirmation. This case report describes the appearance of DI in five Duroc boars in Switzerland. CASE PRESENTATION: Two purebred intact Duroc boars at the age of 8 months and 1.5 years, respectively, with a history of polyuric and polydipsic symptoms had been referred to the Swine Clinic in Berne. Based on the case history, the results of clinical examination and the analysis of blood and urine, a tentative diagnosis of DI was concluded. Finally, the diagnosis was confirmed by findings from a modified water deprivation test, macroscopic examinations and histopathology. Following the diagnosis, three genes known to be involved in inherited DI in humans were analyzed in order to explore a possible genetic background of the affected boars. CONCLUSION: The etiology of DI in pigs is supposed to be the same as in humans, although this disease has never been described in pigs before. Thus, although occurring only on rare occasions, DI should be considered as a differential diagnosis in pigs with polyuria and polydipsia. It seems that a modified water deprivation test may be a helpful tool for confirming a diagnosis in pigs. Since hereditary forms of DI have been described in humans, the occurrence of DI in pigs should be considered in breeding programs although we were not able to identify a disease associated mutation. PMID- 26832363 TI - Patient experience in the treatment of metastatic castration-resistant prostate cancer: state of the science. AB - BACKGROUND: Contemporary therapies for metastatic castration-resistant prostate cancer (mCRPC) have shown survival improvements, which do not account for patient experience and health-related quality of life (HRQoL). METHODS: This literature review included a search of MEDLINE for randomized clinical trials enrolling ?50 patients with mCRPC and reporting on patient-reported outcomes (PROs) since 2010. RESULTS: Nineteen of 25 publications describing seven treatment regimens (10 clinical trials and nine associated secondary analyses) met the inclusion criteria and were critically appraised. The most commonly used measures were the Functional Assessment of Cancer Therapy-Prostate (n=5 trials) and Brief Pain Inventory Short Form (n=4 trials) questionnaires. The published data indicated that HRQoL and pain status augmented the clinical efficacy data by providing a better understanding of treatment impact in mCRPC. Abiraterone acetate and prednisone, enzalutamide, radium-223 dichloride and sipuleucel-T offered varying levels of HRQoL benefit and/or pain mitigation versus their respective comparators, whereas three treatments (mitoxantrone, estramustine phosphate and docetaxel, and cabazitaxel) had no meaningful impact on HRQoL or pain. The main limitation of the data were that the PROs utilized were not developed for use in mCRPC patients and hence may not have comprehensively captured symptoms important to this population. CONCLUSIONS: Recently published randomized clinical trials of new agents for mCRPC have captured elements of the patient experience while on treatment. Further research is required to standardize methods for measuring, quantifying and reporting on HRQoL and pain in patients with mCRPC in the clinical practice setting. PMID- 26832364 TI - A1E reduces stemness and self-renewal in HPV 16-positive cervical cancer stem cells. AB - BACKGROUND: Cervical cancer is the second most common cancer in females. Recent reports have revealed the critical role of cervical cancer stem cells (CSCs) in tumorigenicity and metastasis. Previously we demonstrated that A1E exerts an anti proliferative action, which inhibits the growth of cervical cancer cells. METHODS: A1E is composed of 11 oriental medicinal herbs. Cervical cancer cell culture, wund healing and invasion assay, flow cytometry, sheroid formation assay, and wstern blot assays were performed in HPV 16-positive SiHa cell and HPV 16-negative C33A cells. RESULTS: A1E targets the E6 and E7 oncogenes; thus, A1E significantly inhibited proliferation of human papilloma virus (HPV) 16-positive SiHa cells, it did not inhibit the proliferation of HPV-negative C33A cells. Accordingly, we investigated whether A1E can regulate epithelial-to-mesenchymal transition (EMT), CSC self-renewal, and stemness-related gene expression in cervical cancer cells. Down rgulation of cell migration, cell invasion, and EMT was observed in A1E-treated SiHa cells. Specifically, A1E-treated SiHa cells showed significant decreases in OCT-3/4 and Sox2 expression levels and in sphere formation. Moreover, CSCs makers ALDH+ and ALDH, CD133 double positive cell were significantly decreased in A1E-treated SiHa cells. However, A1E treatment did not down regulate ALDH+ expression and the number of ALDH/CD133 double positive cells in C33A cells. CONCLUSIONS: Taken together, A1E can inhibit CSCs and reduce the expression of stemness markers. Treating CSCs with A1E may be a potential therapy for cervical cancer. PMID- 26832366 TI - Extensive variation in sperm morphology in a frog with no sperm competition. AB - BACKGROUND: Recent comparative studies of several taxa have found that within species variation in sperm size decreases with increasing levels of sperm competition, suggesting that male-male gamete competition selects for an optimal sperm phenotype. Previous studies of intraspecific sperm length variation have all involved internal fertilizers where some other factors-e.g., sperm storage and sperm movement along the walls of the female's reproductive tract-probably also influence and reduce sperm size variation. Thus external fertilizers, where those factors are absent, might be expected to exhibit even more variation when there is little or no sperm competition. To test that idea, we studied the sperm morphology of a North American chorus frog, the spring peeper (Pseudacris crucifer), a species in which males encounter little or no sperm competition. RESULTS: As expected, sperm size was highly variable in the spring peeper, largely due to variation in flagellum length within and among individual males, among populations and between mitochondrial lineages in southwestern Ontario. In addition, a large proportion of spermatozoa in all males was abnormal in such a way that the ability of abnormal spermatozoa to fertilize was probably compromised. There were no differences in the frequencies of abnormalities among populations or mitochondrial lineages. CONCLUSIONS: In the absence of sperm competition, we suggest that genetic drift has probably played a role in the generation of diversity in sperm morphology in this species, potentially resulting in the observed differences among populations. Such interpopulation difference in sperm morphology might be expected to increase the degree of reproductive isolation between populations even before other isolating mechanisms evolve. PMID- 26832365 TI - Fish oil alleviated high-fat diet-induced non-alcoholic fatty liver disease via regulating hepatic lipids metabolism and metaflammation: a transcriptomic study. AB - BACKGROUND: Intake of fish oil rich in n-3 polyunsaturated fatty acids (PUFAs) is believed to be beneficial against development of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms remain unclear. This study was to gain further understanding of the potential mechanisms of the protective effects of fish oil against NAFLD. METHODS: Ten male Sprague-Dawley rats were fed a control diet (CON), a Western style high-fat and high-cholesterol diet (WD), or a WD diet containing fish oil (FOH) for 16 weeks respectively. The development of liver steatosis and fibrosis were verified by histological and biochemical examination. Hepatic transcriptome were extracted for RNA-seq analysis, and particular results were confirmed by real-time polymerase chain reaction (PCR). RESULTS: The consumption of fish oil significantly ameliorated WD-induced dyslipidemia, transaminase elevation, hepatic steatosis, inflammatory infiltration, and fibrosis. Hepatic RNA-Seq analysis showed that long-term intake of fish oil restored the expression of circadian clock-related genes per2 and per3, which were reduced in WD fed animals. Fish oil consumption also corrected the expression levels of genes involved in fatty acid and cholesterol metabolism, such as Srebf1, Fasn, Scd1, Insig2, Cd36, Cyp7a1, Abcg5, Abcg8 and Pcsk9. Moreover, the expression levels of pro-inflammation genes Mcp1, Socs2, Sema4a, and Cd44 in the FOH group were lower than that of WD group, implying that fish oil protects the liver against WD-induced hepatic inflammation. CONCLUSION: The present study demonstrates fish oil protects against WD-induced NALFD via improving lipid metabolism and ameliorating hepatic inflammation. Our findings add to the current understanding on the benefits of n-3 PUFAs against NAFLD. PMID- 26832368 TI - Weapon identification using antemortem CT with 3D reconstruction, is it always possible?--A report in a case of facial blunt and sharp injuries using an ashtray. AB - An interesting case of homicide involving the use of a heavy glass ashtray is described. The victim, a 81-years-old woman, has survived for few days and died in hospital. The external examination of the victim showed extensive blunt and sharp facial injuries and defense injuries on both the hands. The autopsy examination showed numerous tears on the face, as well as multiple fractures of the facial bones. Computer tomography scan, with 3D reconstruction, performed in hospital before death, was used to identify the weapon used for the crime. In recent years new diagnostics tools such as computer tomography has been widely used, especially in cases involving sharp and blunt forces. Computer tomography has proven to be very valuable in analyzing fractures of the cranial teca for forensic purpose, in particular antemortem computer tomography with 3D reconstruction is becoming an important tool in the process of weapon identification, thanks to the possibility to identify and make comparison between the shape of the object used to commit the crime, the injury and the objects found during the investigations. No previous reports on the use of this technique, for the weapon identification process, in cases of isolated facial fractures were described. We report a case in which, despite the correct use of this technique, it was not possible for the forensic pathologist to identify the weapon used to commit the crime. Authors wants to highlight the limits encountered in the use of computer tomography with 3D reconstruction as a tool for weapon identification when facial fractures occurred. PMID- 26832369 TI - Modified DOP-PCR for improved STR typing of degraded DNA from human skeletal remains and bloodstains. AB - Forensic and ancient DNA samples often are damaged and in limited quantity as a result of exposure to harsh environments and the passage of time. Several strategies have been proposed to address the challenges posed by degraded and low copy templates, including a PCR based whole genome amplification method called degenerate oligonucleotide-primed PCR (DOP-PCR). This study assessed the efficacy of four modified versions of the original DOP-PCR primer that retain at least a portion of the 5' defined sequence and alter the number of bases on the 3' end. The use of each of the four modified primers resulted in improved STR profiles from environmentally-damaged bloodstains, contemporary human skeletal remains, American Civil War era bone samples, and skeletal remains of WWII soldiers over those obtained by previously described DOP-PCR methods and routine STR typing. Additionally, the modified DOP-PCR procedure allows for a larger volume of DNA extract to be used, reducing the need to concentrate the sample and thus mitigating the effects of concurrent concentration of inhibitors. PMID- 26832367 TI - Serum levels of 14-3-3eta protein supplement C-reactive protein and rheumatoid arthritis-associated antibodies to predict clinical and radiographic outcomes in a prospective cohort of patients with recent-onset inflammatory polyarthritis. AB - BACKGROUND: Age, C-Reactive Protein (CRP) and autoantibodies (Abs) are associated with worse prognosis in patients with recent-onset inflammatory polyarthritis (EPA). Serum 14-3-3eta protein is a joint-derived biomarker that up-regulates cytokines and enzymes that perpetuate local and systemic inflammation and may contribute to joint damage. Our objective was to evaluate, over a 5-year prospective period of observation, the additional prognostic potential of serum 14-3-3eta protein in EPA patients. METHODS: Clinical variables, serum and radiographs (scored according to the Sharp/van der Heijde (SvH) method) were collected serially. Relationships between serum 14-3-3eta protein and other biomarkers were computed with Spearman correlations. Outcomes were Simple Disease Activity Index (SDAI) scores and joint damage progression: DeltaSvH for SvH score and DeltaErosion for its Erosive component. The additional predictive contribution of 14-3-3eta was defined using generalized estimating equations (GEE) and generalized linear mixed models (GLMM). RESULTS: Among 331 patients, baseline 14-3-3eta was >=0.19 and >=0.50 ng/ml in 153 (46.2 %) and 119 (36.0 %), respectively; CRP was >8.0 mg/L in 207 (62.5 %), and at least one Ab (Rheumatoid Factor, anti-CCP2 or anti-Sa/citrullinated vimentin) was positive in 170 (51.5 %). Elevated 14-3-3eta levels moderately correlated with positive Abs, but not with elevated CRP. Baseline 14-3-3eta >=0.19 ng/ml was associated with more radiographic progression over 5 years. The optimal levels of baseline 14-3-3eta to predict radiographic progression was defined by ROC curves at 0.50 ng/ml. Levels of 14-3-3eta >=0.50 ng/ml at baseline were associated with lower likelihoods of ever reaching SDAI remission (RR 0.79 (95 % CI 0.64-0.98), p = 0.03) and higher subsequent progression of Total and Erosion SvH scores. Elevated levels of 14-3-3eta during follow-up also predicted higher subsequent progression, even in patients in SDAI remission. Decreases of 14-3-3eta levels by at least 0.76 ng/ml and reversion to negative during follow-up associated with less subsequent radiographic progression. In multivariate models, elevated 14-3 3eta interacted with positive Abs, elevated CRP and older age to predict subsequent radiographic progression. CONCLUSIONS: Levels of 14-3-3eta protein >=0.50 ng/ml predict poorer clinical and radiographic outcomes in EPA, both at baseline and after initiation of treatment, even in SDAI remitters. 14-3-3eta, CRP, age and Abs represent independent predictors of subsequent joint damage. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT00512239 . Registered August 6, 2007. PMID- 26832370 TI - Age estimation by an analysis of spheno-occipital synchondrosis using cone-beam computed tomography. AB - The spheno-occipital synchondrosis has a relatively late ossification in comparison with other cranial base synchondroses, which makes it a point of interest for forensic age determination studies. The purpose of the present study was to evaluate the reliability of spheno-occipital synchondrosis development in age determination in a Turkish population and to evaluate the reproducibility and reliability of cone beam computed tomography (CBCT) in an evaluation of the fusion stages of spheno-occipital synchondrosis. CBCT mid-sagittal images of 238 (90 males and 148 females) patients between the ages of 7 and 25, with a mean age of 15.45+/-0.26 and 16.43+/-0.37, respectively, were examined by three Oral and Maxillofacial Radiologists who evaluated the degree of synchondrosis fusion using a four-stage system. A reevaluation of 50 cases was conducted for intraobserver assessment. Multiple statistical analyses were used to assess the correlation between age and the fusion stage, to compare gender and age according to stages, and to evaluate the inter- and intraobserver agreement. The mean ages for complete fusion (Stage 3) were 18 and 20 for females and males, respectively. The interobserver agreement ranged between substantial and perfect, while the intraobserver agreement was substantial for all three observers. Based on these results, CBCT, when available, might be the method of choice for age estimation using the spheno-occipital synchondrosis fusion stages. Evaluating spheno occipital synchondrosis has a value for age estimation around the age of 18 years, which affects the legal decisions in Turkey. PMID- 26832371 TI - Underbelly injury based identification of the driver in a three-rider motorcycle accident. AB - This paper presents a three-rider motorcycle accident which took place in a suburb of Chongqing China. In the accident, the motorcycle impacted the terminal of a bridge footpath and led to two riders died and one rider injured. After the accident, one rider received injuries around the groin area including the underbelly area and the perineum area. Another rider suffered from injuries only on the perineum areas. In medico-legal judgments, injuries around the groin area also called groin injuries in victims of motorcycle accidents are usually regarded as "fuel tank injuries" which are commonly found in drivers. But, the injuries around the groin area are sometimes confused with the perineum injuries. Therefore, the perineum injuries are often wrongly reckoned as the "fuel tank injuries" and used to identify the drivers too. Actually, passengers can sometimes suffer from perineum injuries in many head-on impacting motorcycle accidents. It is of vital matters to understand the differences between groin injuries and perineum injuries so that the real driver who should be responsible for the accident can be recognized. In this paper, the three-rider motorcycle accident was presented and the injury information of the three riders was studied in order to distinguish the real driver from the riders. We consider that the groin injury has some differences with the perineum injury and the latter should not always be related to the driver especially in high-speed head-on impacting motorcycle accidents. In addition, the injury on underbelly areas is important to identify the driver. PMID- 26832372 TI - The importance of post-mortem computed tomography (PMCT) in confrontation with conventional forensic autopsy of victims of motorcycle accidents. AB - Since traffic accidents are an important problem in forensic medicine, there is a constant search for new solutions to help with an investigation process in such cases. In recent years there was a rapid development of post-mortem imaging techniques, especially post-mortem computed tomography (PMCT). In our work we concentrated on a potential advantage of PMCT in cases of motorcycle accident fatalities. The results of forensic autopsy were compared with combined results of the autopsy and PMCT to check in which areas use of these two techniques gives statistically important increase in number of findings. The hypothesis was confirmed in case of pneumothorax and fractures of skull, spine, clavicle, scapula, lower leg bones. As for majority of other bone fractures locations and brain injures there were single cases with pathologies visible only in PMCT, but too few to reach expected level of p-value. In case of injuries of solid organs and soft tissues statistical analysis did not confirmed any advantage of unenhanced PMCT use. On the whole it has been shown that PMCT used as an adjunct to forensic autopsy can cause an increase in information about vitally important regions in case of motorcycle accident fatalities. PMID- 26832373 TI - An alternate method for extracting DNA from environmentally challenged teeth for improved DNA analysis. AB - A grinding-free method to extract DNA from teeth via a direct minimal-invasive retrograde approach to the pulp cavity and dentine was compared to a standard grinding/pulverisation method. This alternate method uses endodontic dental files to access the root canals and pulp cavity for tissue and dentine harvest via the apical end of the roots and avoids mechanical damage to the crown and root morphology. In contrast, other methods require pulverisation of the whole root or tooth, transection or destruction of the occlusal surface to gain access to the DNA in the root canals and pulp chamber. This study compared two methods for preparing dentine powder from the roots of environmentally challenged teeth for forensic DNA analysis. We found that although the filing method was more laborious, and produced less dentine powder, the amount of amplifiable DNA per milligram of powder was substantially higher with the filing method compared to grinding the entire root. In addition, the number of short tandem repeat (STR) alleles detected and the peak height ratios of the STR profiles were notably higher. Although several other methods of extracting DNA-rich tissue from the pulp chamber of teeth have previously been reported, the method presented in this study is minimally invasive, thereby allowing the preservation of tooth and crown morphology. PMID- 26832374 TI - "High-precision, reconstructed 3D model" of skull scanned by conebeam CT: Reproducibility verified using CAD/CAM data. AB - Computed tomography (CT) scanning has recently been introduced into forensic medicine and dentistry. However, the presence of metal restorations in the dentition can adversely affect the quality of three-dimensional reconstruction from CT scans. In this study, we aimed to evaluate the reproducibility of a "high precision, reconstructed 3D model" obtained from a conebeam CT scan of dentition, a method that might be particularly helpful in forensic medicine. We took conebeam CT and helical CT images of three dry skulls marked with 47 measuring points; reconstructed three-dimensional images; and measured the distances between the points in the 3D images with a computer-aided design/computer-aided manufacturing (CAD/CAM) marker. We found that in comparison with the helical CT, conebeam CT is capable of reproducing measurements closer to those obtained from the actual samples. In conclusion, our study indicated that the image reproduction from a conebeam CT scan was more accurate than that from a helical CT scan. Furthermore, the "high-precision reconstructed 3D model" facilitates reliable visualization of full-sized oral and maxillofacial regions in both helical and conebeam CT scans. PMID- 26832375 TI - An autopsy case of cardiac tamponade caused by a ruptured ventricular aneurysm associated with acute myocarditis. AB - We report an autopsy case of hemopericardium caused by rupture of a ventricular aneurysm associated with acute myocarditis in an infant boy aged 2 years and 10 months. Three days before his death, the patient developed fever. On the day of death, he described an urge to defecate and attempted to do so in an upright position. While straining to defecate without success for a prolonged period, he stopped breathing and collapsed. On autopsy, his heart weighed 91.7 g and cardiac tamponade was evident, the pericardial cavity being filled with 140 mL of blood that had come from a 1.5-cm-long rupture in a 2.7*1.5 cm ventricular aneurysm in the posterior left ventricular wall. Patchy grayish-white discoloration was noted in the myocardium. Histologically, CD3-positive T lymphocytic infiltration accompanied by pronounced macrophage infiltration was observed in the myocardium. Hemorrhagic necrosis was detected in the area of the ventricular aneurysm. Staining for matrix metalloproteinase (MMP) expression revealed abundant MMP-2, MMP-7, and MMP-9. Polymerase chain reaction to detect viruses failed to identify any specific causative viruses in the myocardium. In this case of lymphocytic (viral) and histiocytic myocarditis with pronounced macrophage infiltration and upregulation of MMP expression, myocardial remodeling and associated wall weakening had resulted in formation and rupture of an aneurysm. PMID- 26832376 TI - An autopsy case of complete adipocere formation. AB - A car containing a male corpse with complete adipocere formation was found at the bottom of a lake. The deceased had presumably driven into the lake 7 years earlier. The surface of the deceased was unusually hard and firm like a gypsum board, and the entire internal viscera had turned into adipocere. Since the time required for adipocerous changes depends largely on environmental conditions, we considered the key conditions, namely, water temperature, pH, and oxygen content. In our case, cold, acidic water may have delayed adipocere formation, thus necessitating a long period of time for completeness. On the other hand, anoxic conditions and the peculiar environment of a lake bottom presumably contributed to complete adipocere formation. PMID- 26832377 TI - Circular saw-related fatalities: A rare case report, review of the literature, and forensic implications. AB - Fatalities attributed to powered circular saws appear to be vanishingly rare events with highly wounding and rapidly incapacitating effects. When they do occur, they are mainly self-inflicted in nature. We report the suicide committed by a 79-year-old man using a self-made circular table saw. Autopsy confirmed that the man received multiple heterogeneously distributed saw-type impacts to the head and neck resulting in complete amputation of the upper skull and partial beheading. Homemade or modified commercial sawing instruments and the resultant injuries pose a number of forensic challenges starting from the death scene investigation, continuing with technical examinations, and concluding with determining the manner of death. As with all deaths due to sharp force injuries, fatalities involving power tools such as chainsaws, circular, and band saws warrant a high degree of suspicion of criminal activity and require diligence during all phases of the death investigation. PMID- 26832378 TI - Comparison of the injury severity and medical history of disease-related versus trauma-related bicyclist fatalities. AB - The objective of this study was to clarify the relationship between injury severity and mechanism of death in bicycle fatalities resulting from trauma compared with those resulting from disease, to propose effective measures to prevent fatal bicyclist accidents. Autopsy and accident records were reviewed for bicyclist fatalities who had undergone forensic autopsy at the Dokkyo Medical University School of Medicine between September 1999 and March 2014. Victims' health histories, blood alcohol levels, causes of death, mechanisms of injury, Abbreviated Injury Scale (AIS) scores and Injury Severity Scores (ISSs) were determined. Fifty-five bicyclists (43 male and 12 female) with a mean age of 62.5+/-17.3 years were included in this study. Sixteen victims had driven under the influence of alcohol (mean blood concentration of 1.8+/-0.7 mg/ml). Mean ISS was 32.4 and the chest had the highest mean AIS score (2.6), followed by the head (2.1) and the neck (1.8). Thirty-nine victims (70.9%) had died of trauma and 16 had died of disease. The disease-death victims had significantly higher prevalence of having diabetes mellitus, hyperlipidemia, hypertension, heart disease or cerebrovascular diseases (50.0% vs. 22.2%, p=0.03) and a lower rate of drunk driving (6.3% vs. 41.0%, p=0.01) than the trauma-death group. All victims who were affected by disease, and 33.3% of trauma-death victims, had fallen on the road without a vehicle collision (p<0.001). The mean ISS of the trauma-death group was significantly higher than that of the disease-death group (44.0 vs. 4.2, p<0.001). Except for facial injuries, the AIS scores were significantly higher in trauma-death victims than in the disease-death group (p<0.005). To effectively reduce bicyclist fatalities, the authors strongly advocate efforts that will increase compliance with drunk driving prohibitions. For victims of fatal bicycle accidents with a medical history of diseases, a forensic autopsy should be performed to establish a disease-related death while bicycle riding. We must also put into effect preventative safety measures, which take into consideration the physical condition of bicyclists, to reduce the incidence of these types of accidents. PMID- 26832379 TI - Freezing effect on brain density in postmortem CT. AB - Two 60-year-old males were found at their homes whose bodies had deteriorated due to putrefaction. To prevent worm invasion and minimize deterioration, dry ice was used prior to the autopsy investigation. Prior to autopsy, postmortem CT demonstrated a decreased density in brain parenchyma at the dry-iced side, and autopsy revealed deteriorated brain parenchyma with frozen effect (presented like sherbet). Moreover, the deteriorated cerebral parenchyma maintained their structure and they were evaluated by cutting. When lower CT density presents in postmortem CT, the freezing effect may need to be considered and the physician should evaluate the cadaver's postmortem condition to prevent misdiagnoses. PMID- 26832380 TI - Forensic and population genetic characteristics of 62 X chromosome SNPs revealed by multiplex PCR and MALDI-TOF mass spectrometry genotyping in 4 North Eurasian populations. AB - X chromosome genetic markers are widely used in basic population genetic research as well as in forensic genetics. In this paper we analyze the genetic diversity of 62 X chromosome SNPs in 4 populations using multiplex genotyping based on multi-locus PCR and MALDI-TOF mass spectrometry, and report forensic and population genetic features of the panel of X-linked SNPs (XSNPid). Studied populations represent Siberian (Buryat and Khakas), North Asian (Khanty) and Central Asian (Kazakh) native people. Khanty, Khakas and Kazakh population demonstrate average gene diversity over 0.45. Only East Siberian Buryat population is characterized by lower average heterozygosity (0.436). AMOVA analysis of genetic structure reveals a relatively low but significant level of genetic differentiation in a group of 4 population studied (FST=0.023, p=0.0000). The XSNPid panel provides a very high discriminating power in each population. The combined probability of discrimination in females (PDf) for XSNPid panel ranged between populations from 0.99999999999999999999999982 in Khakas to 0.9999999999999999999999963 in Buryats. The combined discriminating power in males (PDm) varies from 0.999999999999999792 to 0.9999999999999999819. The developed multiplex set of X chromosome SNPs can be a useful tool for population genetic studies and for forensic identity and kinship testing. PMID- 26832381 TI - Effects of using the GlobalFilerTM multiplex system on parent-child analyses of cases with single locus inconsistency. AB - Parent-child analyses sometimes reveal inconsistency of shared alleles at only one locus. This is conventionally called "single locus exclusion", which results from mutational events and the presence of null alleles. Here, in parent-child analyses of the Japanese population, we detected exclusions by using the GlobalFilerTM system comprising 21 short tandem repeat loci. One- or two-step mutations resulting from strand slippage causing gain or loss were observed in seven of 221 parent-child transmissions. The incidences of single locus inconsistency of alleles were 5.88*10(-2) and 8.40*10(-3) for paternal and maternal relationships, respectively. With calculation using a set of 15 loci in the Identifiler(r) multiplex system, the combined likelihood ratio (CLR) values were limited to less than 100 in all five cases accompanied by single inconsistency. The addition of six loci recovered the CLR values to over 10,000 in three cases. Application of this advanced system may increase the detected occurrence of mutational events, but it should be beneficial for inference in parent-child analyses, particularly in cases accompanied by genetic inconsistency. PMID- 26832382 TI - Stature estimation from skull measurements using multidetector computed tomographic images: A Japanese forensic sample. AB - The aim of this study was to assess the correlation between stature and cranial measurements in a contemporary Japanese population, using three-dimensional (3D) computed tomographic (CT) images. A total of 228 cadavers (123 males, 105 females) underwent postmortem CT scanning and subsequent forensic autopsy between May 2011 and April 2015. Five cranial measurements were taken from 3D CT reconstructed images that extracted only cranial data. The correlations between stature and each of the cranial measurements were assessed with Pearson product moment correlation coefficients. Simple and multiple regression analyses showed significant correlations between stature and cranial measurements. In conclusion, cranial measurements obtained from 3D CT images may be useful for forensic estimation of the stature of Japanese individuals, particularly in cases where better predictors, such as long bones, are not available. PMID- 26832383 TI - Effects of storage conditions on forensic examinations of blood samples and bloodstains stored for 20 years. AB - The effects of various storage conditions on blood identification tests, DNA degradation, and short tandem repeat (STR) typing were evaluated. Bloodstains stored at room temperature, 4 degrees C, -20 degrees C, and -80 degrees C for 20 years; blood samples stored at -20 degrees C and -80 degrees C for 20 years; and fresh blood samples were analyzed. Leuco-malachite-green testing, anti-human hemoglobin (Hb) testing (using immunochromatography), and tests for hemoglobin beta (HBB) mRNA were performed as blood identification tests. DNA degradation was evaluated by quantifying the ratios of 305 and 129 base pair (bp) fragments to 41 bp fragments. STR typing was performed using an AmpFlSTR(r) IdentifilerTM Plus PCR Amplification Kit. All samples were positive in leuco-malachite-green staining and anti-human Hb assays. HBB was not detected in blood samples stored at -20 degrees C or -80 degrees C, although this marker was detected in all bloodstains. As indicated by the ratio of 129:41 bp and 305:41 bp DNA fragments, DNA from bloodstains stored at room temperature or 4 degrees C were significantly degraded compared to DNA from all other samples. STR typing analyses revealed that a portion of the loci was undetected in bloodstains stored at room temperature. Therefore, to prevent DNA degradation during long-term storage, it is recommended that bloodstains and blood be stored at below -20 degrees C. In addition, because bloodstains are more suitable for detection of blood-specific mRNAs than blood sample, it is desirable that blood is stored as bloodstain for this method. PMID- 26832384 TI - Micro computed tomography features of laryngeal fractures in a case of fatal manual strangulation. AB - Cases of subtle fatal neck compression are often complicated by the lack of specificity of the post-mortem signs of asphyxia and by the lack of clear signs of neck compression. Herein we present a forensic case of a 45-year-old schizophrenic patient found on the floor of the bedroom of a psychiatric ward in cardiopulmonary arrest and who died after two days in a vegetative state. The deposition of the roommate of the deceased, who claimed responsibility for the killing of the victim by neck compression, was considered unreliable by the prosecutor. Autopsy, toxicological analyses, and multi-slice computed tomography (MSCT), micro computed tomography (micro-CT) and histology of the larynx complex were performed. Particularly, micro-CT analysis of the thyroid cartilage revealed the bilateral presence of ossified triticeous cartilages and the complete fragmentation of the right superior horn of the thyroid, but it additionally demonstrated a fracture on the contralateral superior horns, which was not clearly diagnosable at MSCT. On the basis of the evidence of intracartilaginous laryngeal hemorrhages and bilateral microfracture at the base of the superior horns of the larynx, the death was classified as a case of asphyxia due to manual strangulation. Micro-CT was confirmed as a useful tool in cases of subtle fatal neck compression, for the detection of minute laryngeal cartilage fractures, especially in complex cases with equivocal findings on MSCT. PMID- 26832385 TI - Exploring the controversy in child abuse pediatrics and false accusations of abuse. AB - There is a controversy in child abuse pediatrics between an established corps of child abuse pediatricians aligned with hospital colleagues and law enforcement, and a multi-specialty challenger group of doctors and other medical professionals working with public interest lawyers. The latter group questions the scientific validity of the core beliefs of child abuse pediatricians and believes that there are a substantial number of false accusations of abuse occurring. An unproven primary hypothesis, crafted around 1975 by a small group of pediatricians with an interest in child abuse, lies at the foundation of child abuse pediatrics. With no scientific study, it was hypothesized that subdural hemorrhage (SDH) and retinal hemorrhage (RH) were diagnostic of shaking abuse. That hypothesis became the so-called "shaken baby syndrome." Through the period 1975-1985, in a coordinated manner, these child abuse specialists coalesced under the American Academy of Pediatrics and began working with district attorneys and social workers, informing them of the ways in which their hypothesis could be applied to prosecutions of child abuse and life-altering social service interventions. In a legal context, using then-prevailing evidentiary rules which treated scientific expert testimony as valid if it was "generally accepted" in the field, they represented falsely that there was general acceptance of their hypothesis and therefore it was valid science. As the ability to convict based on this unproven prime hypothesis (SDH and RH equals abuse) increased, some defense attorneys were professionally compelled by their own doubts to reach out to experts from other fields with experience with SDH and RH, trauma, and biomechanics, for second opinions. Medical and legal challenges to the established thinking soon emerged, based on both old and new evidenced-based literature. As the intensity of the controversy increased, the probability of false accusation became more apparent and the need to address the issue more pressing. Since false accusations of child abuse are themselves abusive, efforts to eliminate such false accusations must continue. PMID- 26832386 TI - Usefulness and limitations of postmortem computed tomography in forensic analysis of gunshot injuries: Three case reports. AB - Gunshot injury has always been an important field of investigation in postmortem forensic radiology. The localization and retrieval of the bullet and of potentially important fragments are vital to these cases. Using postmortem multidetector-row computed tomography (MDCT) prior to forensic autopsy, we sought to illustrate the importance of this modality in the noninvasive characterization of gunshot wounds. We obtained and analyzed MDCT images in three cases of gunshot wounds (accidental close-range shotgun shooting, suicidal contact gunshot to the head and accidental long-range buckshot shooting). We discuss the value of postmortem MDCT findings in gunshot wound cases by comparing with forensic autopsy findings in Japan, a developing country with miserably low autopsy rate. PMID- 26832387 TI - Usual Care for Adolescent Depression From Symptom Identification Through Treatment Initiation. AB - IMPORTANCE: Published guidelines describing effective adolescent depression care in primary care settings include screening, assessment, treatment initiation, and symptom monitoring. It is unclear the extent to which these steps are documented in patient health records. OBJECTIVE: To determine rates of appropriate follow-up care for adolescents with newly identified depression symptoms in 3 large health systems. DESIGN, SETTING, AND PARTICIPANTS: In this analysis conducted from March to September 2014, structured data retrospectively extracted from electronic health records were analyzed for 3 months following initial symptom identification to determine whether the patient was followed up and, if so, whether treatment was initiated and/or symptoms were monitored. Records were collected from 2 large health maintenance organizations in the western United States and a network of community health centers in the Northeast. The study group included adolescents (N = 4612) with newly identified depression symptoms, defined as an elevated score on the Patient Health Questionnaire (>= 10) and/or a diagnosis of depression. MAIN OUTCOMES AND MEASURES: Rates of treatment initiation, symptom monitoring, and follow-up care documented within 3 months of initial symptom identification. RESULTS: Among the 4612 participants, the mean (SD) age at index event was 16.0 (2.3) years, and 3060 were female (66%). Treatment was initiated for nearly two-thirds of adolescents (79% of those with a diagnosis of major depression; n = 023); most received psychotherapy alone or in combination with medications. However, in the 3 months following identification, 36% of adolescents received no treatment (n = 1678), 68% did not have a follow-up symptom assessment (n = 3136), and 19% did not receive any follow-up care (n = 854). Further, 40% of adolescents prescribed antidepressant medication did not have any documentation of follow-up care for 3 months (n = 356). Younger age (ages 15-17 years: odds ratio [OR], 0.78; 95% CI, 0.67-0.92 and ages 18-20 years: OR, 0.83; 95% CI, 0.70-0.99; P = .008), more severe initial symptoms (moderate: OR, 0.99; 95% CI, 0.82-1.21; moderate to severe: OR, 1.46; 95% CI, 1.19-1.80; and severe: OR, 2.14; 95% CI, 1.65-2.79; P < .001), and receiving a diagnosis (major depression/dysthymia: OR, 2.65; 95% CI, 2.20-3.20 and unspecified depression/adjustment disorder: OR, 1.75; 95% CI, 1.43-2.14; P < .001) were significantly associated with treatment initiation. Differences in rates of follow-up care were evident between sites (site 2: OR, 1.77; 95% CI, 1.45-2.16 and site 3: OR, 2.10; 95% CI, 1.72-2.57), suggesting that differences within health systems may also affect care received. CONCLUSIONS AND RELEVANCE: Most adolescents with newly identified depression symptoms received some treatment, usually including psychotherapy, within the first 3 months after identification. However, follow-up care was low and substantial variation existed between sites. These results raise concerns about the quality of care for adolescent depression. PMID- 26832388 TI - Further significant effects of eldecalcitol on bone resorption markers and bone mineral density in postmenopausal osteoporosis patients having undergone long term bisphosphonate treatment. AB - We investigated whether eldecalcitol has further significant effects on bone metabolic markers and bone mineral density (BMD) in osteoporosis patients having undergone long-term bisphosphonate treatment. Eldecalcitol treatment was initiated in 48 postmenopausal osteoporosis patients who had undergone bisphosphonate treatment with or without alfacalcidol treatment for more than 2 years (average period 6.3 years). Age, height, weight, total muscle volume, total fat volume, estimated glomerular filtration rate, and BMD at the lumbar spine, total hip, and distal third of the radius were measured as background data for each patient. Serum alkaline phosphatase, tartrate-resistant acid phosphatase 5b, calcium, and phosphate levels were measured at the baseline and 3 and 12 months after the initiation of eldecalcitol treatment, and BMD was measured at the baseline and 12 months after the initiation of eldecalcitol treatment. Tartrate resistant acid phosphatase 5b level was significantly decreased at 3 and 12 months after the initiation of eldecalcitol treatment in comparison with the baseline level. There were no significant changes in alkaline phosphatase, calcium, or phosphate levels in comparison with the baseline levels. In addition, the lumbar spine BMD at 12 months after the initiation of treatment was significantly increased in comparison with the baseline level, although no significant changes in BMD at the total hip and distal third of the radius were observed. Eldecalcitol demonstrated significant effects in additionally decreasing the level of the bone resorption marker tartrate-resistant acid phosphatase 5b and increasing BMD at the lumbar spine, even in osteoporosis patients having undergone long-term bisphosphonate treatment. PMID- 26832390 TI - Hollywood, industry, and critical care. PMID- 26832389 TI - Vitamin D-binding protein, vitamin D status and serum bioavailable 25(OH)D of young Asian Indian males working in outdoor and indoor environments. AB - Urban Asian Indians generally have low serum 25(OH)D. Information on serum bioavailable 25(OH)D and the effect of prolonged sun-exposure in them is not known. We assessed serum 25(OH)D and bioavailable 25(OH)D in males with varying durations of sun-exposure in Delhi during August-September. Serum 25(OH)D, vitamin D-binding protein (DBP), bioavailable 25(OH)D, free 25(OH)D index, iPTH, ionized calcium and sun-index were assessed in outdoor, mixed outdoor-indoor and indoor workers (n = 88, 32 and 74, respectively). The mean sun-index (12.0 +/- 6.25, 4.3 +/- 2.20 and 0.7 +/- 0.62, respectively; P < 0.001) was highest outdoors and lowest indoors. Serum 25(OH)D (29.0 +/- 8.61, 19.1 +/- 5.73 and 10.9 +/- 4.19 ng/ml, respectively; P < 0.001), bioavailable 25(OH)D and free 25(OH)D index were maximum in outdoor workers followed by mixed-exposure and indoor workers. Their mean serum DBP levels (241.2 +/- 88.77, 239.3 +/- 83.40 and 216.6 +/- 63.93 ug/ml, respectively; P = 0.12) were comparable. Mean serum iPTH was significantly lower in outdoor than indoor workers and showed inverse correlations with serum 25(OH)D, bioavailable 25(OH)D and free 25(OH)D index (r = -0.401, -0.269 and -0.236, respectively; P < 0.001 in all). Daily dietary-calorie intake was higher and calcium lower in outdoor than indoor workers. On regression analysis, sun-exposure was the only significant variable, increasing serum 25(OH)D by 2.03 ng/ml per hour of sun-exposure (95 % confidence interval 1.77 2.28; P < 0.001). Outdoor workers with prolonged sun-exposure were vitamin D sufficient, with higher serum bioavailable 25(OH)D than the indoor workers during summer. Use of serum DBP levels did not affect the interpretation of their vitamin D status. PMID- 26832391 TI - Prediction of elbow joint contact mechanics in the multibody framework. AB - Computational multibody musculoskeletal models of the elbow joint that are capable of simultaneous and accurate predictions of muscle and ligament forces, along with cartilage contact mechanics can be immensely useful in clinical practice. As a step towards producing a musculoskeletal model that includes the interaction between cartilage and muscle loading, the goal of this study was to develop subject-specific multibody models of the elbow joint with discretized humerus cartilage representation interacting with the radius and ulna cartilages through deformable contacts. The contact parameters for the compliant contact law were derived using simplified elastic foundation contact theory. The models were then validated by placing the model in a virtual mechanical tester for flexion extension motion similar to a cadaver experiment, and the resulting kinematics were compared. Two cadaveric upper limbs were used in this study. The humeral heads were subjected to axial motion in a mechanical tester and the resulting kinematics from three bones were recorded for model validation. The maximum RMS error between the predicted and measured kinematics during the complete testing cycle was 2.7 mm medial-lateral translation and 9.7 degrees varus-valgus rotation of radius relative to humerus (for elbow 2). After model validation, a lateral ulnar collateral ligament (LUCL) deficient condition was simulated and, contact pressures and kinematics were compared to the intact elbow model. A noticeable difference in kinematics, contact area, and contact pressure were observed for LUCL deficient condition. LUCL deficiency induced higher internal rotations for both the radius and ulna during flexion and an associated medial shift of the articular contact area. PMID- 26832392 TI - Design and evaluation of an actuated knee implant for postoperative ligament imbalance correction. AB - In Total Knee Arthroplasty (TKA), the collateral ligament tensioning stage cannot be standardised for all patients and relies heavily on the surgeon's experience and perception. Intraoperative inaccuracies are practically unavoidable and may give rise to severe postoperative complications, leading to the need for revision surgery already a few years after primary TKA. This work proposes a novel instrumented tibial component able to detect collateral ligament laxity conditions right after primary TKA and, if needed, to compensate for them in the postoperative period. A miniaturised actuation system, designed to be embedded in the tibial baseplate, was initially evaluated by means of 3D simulations and then fabricated as a full-scale prototype. Stability and force sensors tests carried out on a knee simulator allowed to assess the effectiveness of the proposed design under normal working conditions and provided valuable insights for future work and improvements. PMID- 26832393 TI - Intensified organics and nitrogen removal in the intermittent-aerated constructed wetland using a novel sludge-ceramsite as substrate. AB - In this study, a novel sludge-ceramsite was applied as main substrate in intermittent-aerated subsurface flow constructed wetlands (SSF CWs) for treating decentralized domestic wastewater, and intensified organics and nitrogen removal in different SSF CWs (with and without intermittent aeration, with and without sludge-ceramsite substrate) were evaluated. High removal of 97.2% COD, 98.9% NH4(+)-N and 85.8% TN were obtained simultaneously in the intermittent-aerated CW system using sludge-ceramsite substrate compared with non-aerated CWs. Moreover, results from fluorescence in situ hybridization (FISH) analysis revealed that the growth of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) in the intermittent-aerated CW system with sludge-ceramsite substrate was enhanced, thus indicating that the application of intermittent aeration and sludge-ceramsite plays an important role in nitrogen transformations. These results suggest that a combination of intermittent aeration and sludge-ceramsite substrate is reliable to enhance the treatment performance in SSF CWs. PMID- 26832394 TI - Formation and degradation of valuable intermediate products during wet oxidation of municipal sludge. AB - The current study investigated the formation of organic acids and alcohols as major intermediate products of wet oxidation of municipal sludge. Municipal sludge was subjected to 60-min wet oxidation at temperatures ranging from 220 to 240 degrees C, with 20bar oxygen partial pressure. Acetic acid was the main intermediate compound produced in this study, followed by propionic, n-butyric, iso-butyric and pentanoic acids and methanol. It was found that the process severity has a significant influence on the formation and degradation of these intermediate products. PMID- 26832395 TI - Solid-state anaerobic digestion of lignocellulosic biomass: Recent progress and perspectives. AB - Solid-state anaerobic digestion (SS-AD), which has gained popularity in the past decade as an environmentally friendly and cost-effective technology for extracting energy from various types of lignocellulosic biomass, is reviewed in this paper. According to data of biomass and methane yields of lignocellulosic feedstocks, crop residues have the highest methane production potential in the U.S., followed by the organic fraction of municipal solid waste (OFMSW), forestry waste, and energy crops. Methane yield and process stability of SS-AD can be improved by different strategies, such as co-digestion with other organic wastes, pretreatment of lignocellulosic biomass, and optimization of operating parameters. Different models for SS-AD have been developed, and insights into SS AD processes have been obtained via microbial community analysis, microscope imaging, and tracer techniques. Future research and development in SS-AD, including feedstock identification and co-digestion, feedstock storage and pretreatment, SS-AD reactor development, digestate treatment, and value-added production, are recommended. PMID- 26832396 TI - Zika Virus: Rapid Spread in the Western Hemisphere. PMID- 26832398 TI - Gastrospheres of human gastric mucosa cells: an in vitro model of stromal and epithelial stem cell niche reconstruction. AB - The molecular characterization of mechanisms involved in the gastrointestinal tract disorders needs an in vitro 3D culture model able to mimic the in vivo gastric microenvironment. Herein, we propose a 3D coculture system where gastric epithelial and stromal cells are grown together building spherical and solid structures using the NASA bioreactor - cell culture system (RCCS), a bioreactor. Epithelial and stromal cells from human antral gastric mucosa were isolated from endoscopic gastric biopsies. Thereafter, these cells were mechanically and enzymatically dispersed by treatment with dispase and collagenase, respectively. Using specific culture procedures, these cells formed 3D structures by using a RCCS, named "gastrospheres". Briefly, gastrospheres were obtained by initial seeding of 2.5x104 cells/well in 96 well culture plates. At 24 h after their formation, they were transferred into RCCS, and maintained for 7, 14, 21, and 28 days. The gastrospheres were morphologically characterized by immunocytochemisty to evaluate extracellular matrix (ECM), and by electron microscopy. These analysis of gastrospheres revealed that the epithelial cells were cytokeratin (CK) and lectin reactive and were arranged in the outer layer; stromal cells presented long cytoplasmic processes and were localized inside the gastrosphere. They were vimentin (VIM) and alpha-smooth muscle actin (alpha-SMA) positive and expressed ECM components such as laminin (LN), fibronectin (FN), and type IV collagen (CIV). Electron microscopy revealed groups of cohesive gastric cells surrounded by complex stromal structures, with multiple microvilli, and tight cellular junctions interspersed with extracellular matrix fibrils and fibers. The presence of some nestin-positive cells was observed in the inner region of the gastrospheres, suggesting an intermediary localization between epithelial and stromal cells. Altogether, our data suggest that in vitro gastrospheres recapitulate the in vivo gastric niche microenvironment. PMID- 26832397 TI - Touch and go: nuclear proteolysis in the regulation of metabolic genes and cancer. AB - The recruitment of transcription factors to promoters and enhancers is a critical step in gene regulation. Many of these proteins are quickly removed from DNA after they completed their function. Metabolic genes in particular are dynamically regulated and continuously adjusted to cellular requirements. Transcription factors controlling metabolism are therefore under constant surveillance by the ubiquitin-proteasome system, which can degrade DNA-bound proteins in a site-specific manner. Several of these metabolic transcription factors are critical to cancer cells, as they promote uncontrolled growth and proliferation. This review highlights recent findings in the emerging field of nuclear proteolysis and outlines novel paradigms for cancer treatment, with an emphasis on multiple myeloma. PMID- 26832399 TI - Nac1 Coordinates a Sub-network of Pluripotency Factors to Regulate Embryonic Stem Cell Differentiation. AB - Pluripotent cells give rise to distinct cell types during development and are regulated by often self-reinforcing molecular networks. How such networks allow cells to differentiate is less well understood. Here, we use integrative methods to show that external signals induce reorganization of the mouse embryonic stem cell pluripotency network and that a sub-network of four factors, Nac1, Oct4, Tcf3, and Sox2, regulates their differentiation into the alternative mesendodermal and neuroectodermal fates. In the mesendodermal fate, Nac1 and Oct4 were constrained within quantitative windows, whereas Sox2 and Tcf3 were repressed. In contrast, in the neuroectodermal fate, Sox2 and Tcf3 were constrained while Nac1 and Oct4 were repressed. In addition, we show that Nac1 coordinates differentiation by activating Oct4 and inhibiting both Sox2 and Tcf3. Reorganization of progenitor cell networks around shared factors might be a common differentiation strategy and our integrative approach provides a general methodology for delineating such networks. PMID- 26832402 TI - CCR7 Controls Thymus Recirculation, but Not Production and Emigration, of Foxp3(+) T Cells. AB - Current models of Foxp3(+) regulatory T cell (Treg) development involve CCR7 mediated migration of thymocytes into the thymus medulla to enable essential interactions with medullary epithelium. However, increased Foxp3(+) thymic Treg numbers in Ccr7(-/-) mice challenge this view, and the role of CCR7 in Treg development, emigration, and/or recirculation is unknown. Here, we have examined CCR7 and Rag2pGFP levels during Treg development and generated Rag2pGFPCcr7(-/-) mice to study its impact on the intrathymic Treg pool. We reveal surprising developmental heterogeneity in thymocytes described as Treg precursors, showing that they contain recirculating CCR6(+)CCR7(-)Rag2pGFP(-) T cells. Although CCR7 defines bona fide Rag2GFP(+) Treg precursors, it is not required for Treg production and emigration. Rather, we show that lack of CCR7 renders the thymus more receptive to Treg thymus homing. Our study reveals a role for CCR7 in limiting Treg recirculation back to the thymus and enables separation of the mechanisms controlling Treg production and thymic recirculation. PMID- 26832400 TI - APOBEC3A and APOBEC3B Preferentially Deaminate the Lagging Strand Template during DNA Replication. AB - APOBEC family cytidine deaminases have recently been implicated as powerful mutators of cancer genomes. How APOBECs, which are ssDNA-specific enzymes, gain access to chromosomal DNA is unclear. To ascertain the chromosomal ssDNA substrates of the APOBECs, we expressed APOBEC3A and APOBEC3B, the two most probable APOBECs mediating cancer mutagenesis, in a yeast model system. We demonstrate, using mutation reporters and whole genome sequencing, that APOBEC3A- and APOBEC3B-induced mutagenesis primarily results from the deamination of the lagging strand template during DNA replication. Moreover, our results indicate that both genetic deficiencies in replication fork-stabilizing proteins and chemical induction of replication stress greatly augment the mutagenesis of APOBEC3A and APOBEC3B. Taken together, these results strongly indicate that ssDNA formed during DNA lagging strand synthesis is a major substrate for APOBECs and may be the principal substrate in human cancers experiencing replication stress. PMID- 26832401 TI - Inborn Errors of Long-Chain Fatty Acid beta-Oxidation Link Neural Stem Cell Self Renewal to Autism. AB - Inborn errors of metabolism (IEMs) occur with high incidence in human populations. Especially prevalent among these are inborn deficiencies in fatty acid beta-oxidation (FAO), which are clinically associated with developmental neuropsychiatric disorders, including autism. We now report that neural stem cell (NSC)-autonomous insufficiencies in the activity of TMLHE (an autism risk factor that supports long-chain FAO by catalyzing carnitine biosynthesis), of CPT1A (an enzyme required for long-chain FAO transport into mitochondria), or of fatty acid mobilization from lipid droplets reduced NSC pools in the mouse embryonic neocortex. Lineage tracing experiments demonstrated that reduced flux through the FAO pathway potentiated NSC symmetric differentiating divisions at the expense of self-renewing stem cell division modes. The collective data reveal a key role for FAO in controlling NSC-to-IPC transition in the mammalian embryonic brain and suggest NSC self renewal as a cellular mechanism underlying the association between IEMs and autism. PMID- 26832403 TI - Host-Microbiota Interactions in the Pathogenesis of Antibiotic-Associated Diseases. AB - Improved understanding of the interplay between host and microbes stands to illuminate new avenues for disease diagnosis, treatment, and prevention. Here, we provide a high-resolution view of the dynamics between host and gut microbiota during antibiotic-induced intestinal microbiota depletion, opportunistic Salmonella typhimurium and Clostridium difficile pathogenesis, and recovery from these perturbed states in a mouse model. Host-centric proteome and microbial community profiles provide a nuanced longitudinal view, revealing the interdependence between host and microbiota in evolving dysbioses. Time- and condition-specific molecular and microbial signatures are evident and clearly distinguished from pathogen-independent inflammatory fingerprints. Our data reveal that mice recovering from antibiotic treatment or C. difficile infection retain lingering signatures of inflammation, despite compositional normalization of the microbiota, and host responses could be rapidly and durably relieved through fecal transplant. These experiments demonstrate insights that emerge from the combination of these orthogonal, untargeted approaches to the gastrointestinal ecosystem. PMID- 26832404 TI - Centrosome-Dependent Bypass of the DNA Damage Checkpoint by the Polo Kinase Cdc5. AB - Cell-cycle checkpoints are essential feedback mechanisms that promote genome integrity. However, in the face of unrepairable DNA lesions, bypass mechanisms can suppress checkpoint activity and allow cells to resume proliferation. The molecular mechanisms underlying this biological response are currently not understood. Taking advantage of unique separation-of-function mutants, we show that the Polo-like kinase (PLK) Cdc5 uses a phosphopriming-based interaction mechanism to suppress G2/M checkpoint arrest by targeting Polo kinase activity to centrosomes. We also show that key subunits of the evolutionarily conserved RSC complex are critical downstream effectors of Cdc5 activity in checkpoint suppression. Importantly, the lethality and checkpoint defects associated with loss of Cdc5 Polo box activity can be fully rescued by artificially anchoring Cdc5 kinase domain to yeast centrosomes. Collectively, our results highlight a previously unappreciated role for centrosomes as key signaling centers for the suppression of cell-cycle arrest induced by persistent or unrepairable DNA damage. PMID- 26832405 TI - Fin1-PP1 Helps Clear Spindle Assembly Checkpoint Protein Bub1 from Kinetochores in Anaphase. AB - The spindle assembly checkpoint (SAC) monitors chromosome attachment defects, and the assembly of SAC proteins at kinetochores is essential for its activation, but the SAC disassembly process remains unknown. We found that deletion of a 14-3-3 protein, Bmh1, or hyperactivation of Cdc14 early anaphase release (FEAR) allows premature SAC silencing in budding yeast, which depends on a kinetochore protein Fin1 that forms a complex with protein phosphatase PP1. Previous works suggest that FEAR-dependent Fin1 dephosphorylation promotes Bmh1-Fin1 dissociation, which enables kinetochore recruitment of Fin1-PP1. We found persistent kinetochore association of SAC protein Bub1 in fin1Delta mutants after anaphase entry. Therefore, we revealed a mechanism that clears SAC proteins from kinetochores. After anaphase entry, FEAR activation promotes kinetochore enrichment of Fin1 PP1, resulting in SAC disassembly at kinetochores. This mechanism is required for efficient SAC silencing after SAC is challenged, and untimely Fin1-kinetochore association causes premature SAC silencing and chromosome missegregation. PMID- 26832406 TI - The Transcription Factor ASCIZ and Its Target DYNLL1 Are Essential for the Development and Expansion of MYC-Driven B Cell Lymphoma. AB - How MYC promotes the development of cancer remains to be fully understood. Here, we report that the Zn(2+)-finger transcription factor ASCIZ (ATMIN, ZNF822) synergizes with MYC to activate the expression of dynein light chain (DYNLL1, LC8) in the murine EMU-Myc model of lymphoma. Deletion of Asciz or Dynll1 prevented the abnormal expansion of pre-B cells in pre-cancerous EMU-Myc mice and potentiated the pro-apoptotic activity of MYC in pre-leukemic immature B cells. Constitutive loss of Asciz or Dynll1 delayed lymphoma development in EMU-Myc mice, and induced deletion of Asciz in established lymphomas extended the survival of tumor-bearing mice. We propose that ASCIZ-dependent upregulation of DYNLL1 levels is essential for the development and expansion of MYC-driven lymphomas by enabling the survival of pre-neoplastic and malignant cells. PMID- 26832407 TI - Rapid Changes in the Translatome during the Conversion of Growth Cones to Synaptic Terminals. AB - A common step in the formation of neural circuits is the conversion of growth cones to presynaptic terminals. Characterizing patterns of global gene expression during this process is problematic due to the cellular diversity of the brain and the complex temporal dynamics of development. Here, we take advantage of the synchronous conversion of Drosophila photoreceptor growth cones into presynaptic terminals to explore global changes in gene expression during presynaptic differentiation. Using a tandemly tagged ribosome trap (T-TRAP) and RNA sequencing (RNA-seq) at multiple developmental times, we observed dramatic changes in coding and non-coding RNAs with presynaptic differentiation. Marked changes in the mRNA encoding transmembrane and secreted proteins occurred preferentially. The 3' UTRs of transcripts encoding synaptic proteins were preferentially lengthened, and these extended UTRs were preferentially enriched for sites recognized by RNA binding proteins. These data provide a rich resource for uncovering the regulatory logic underlying presynaptic differentiation. PMID- 26832409 TI - Loss of Survivin in Intestinal Epithelial Progenitor Cells Leads to Mitotic Catastrophe and Breakdown of Gut Immune Homeostasis. AB - A tightly regulated balance of proliferation and cell death of intestinal epithelial cells (IECs) is essential for maintenance of gut homeostasis. Survivin is highly expressed during embryogenesis and in several cancer types, but little is known about its role in adult gut tissue. Here, we show that Survivin is specifically expressed in transit-amplifying cells and Lgr5(+) stem cells. Genetic loss of Survivin in IECs resulted in destruction of intestinal integrity, mucosal inflammation, and death of the animals. Survivin deletion was associated with decreased epithelial proliferation due to defective chromosomal segregation. Moreover, Survivin-deficient animals showed induced phosphorylation of p53 and H2AX and increased levels of cell-intrinsic apoptosis in IECs. Consequently, induced deletion of Survivin in Lgr5(+) stem cells led to cell death. In summary, Survivin is a key regulator of gut tissue integrity by regulating epithelial homeostasis in the stem cell niche. PMID- 26832408 TI - Drosophila Lung Cancer Models Identify Trametinib plus Statin as Candidate Therapeutic. AB - We have developed a Drosophila lung cancer model by targeting Ras1(G12V)--alone or in combination with PTEN knockdown--to the Drosophila tracheal system. This led to overproliferation of tracheal tissue, formation of tumor-like growths, and animal lethality. Screening a library of FDA-approved drugs identified several that improved overall animal survival. We explored two hits: the MEK inhibitor trametinib and the HMG-CoA reductase inhibitor fluvastatin. Oral administration of these drugs inhibited Ras and PI3K pathway activity, respectively; in addition, fluvastatin inhibited protein prenylation downstream of HMG-CoA reductase to promote survival. Combining drugs led to synergistic suppression of tumor formation and rescue lethality; similar synergy was observed in human A549 lung adenocarcinoma cells. Notably, fluvastatin acted both within transformed cells and also to reduce whole-body trametinib toxicity in flies. Our work supports and provides further context for exploring the potential of combining statins with MAPK inhibitors such as trametinib to improve overall therapeutic index. PMID- 26832410 TI - Single-Cell Gene Expression Analyses Reveal Heterogeneous Responsiveness of Fetal Innate Lymphoid Progenitors to Notch Signaling. AB - T and innate lymphoid cells (ILCs) share some aspects of their developmental programs. However, although Notch signaling is strictly required for T cell development, it is dispensable for fetal ILC development. Constitutive activation of Notch signaling, at the common lymphoid progenitor stage, drives T cell development and abrogates ILC development by preventing Id2 expression. By combining single-cell transcriptomics and clonal culture strategies, we characterize two heterogeneous alpha4beta7-expressing lymphoid progenitor compartments. alphaLP1 (Flt3(+)) still retains T cell potential and comprises the global ILC progenitor, while alphaLP2 (Flt3(-)) consists of ILC precursors that are primed toward the different ILC lineages. Only a subset of alphaLP2 precursors is sensitive to Notch signaling required for their proliferation. Our study identifies, in a refined manner, the diversity of transitional stages of ILC development, their transcriptional signatures, and their differential dependence on Notch signaling. PMID- 26832411 TI - Tead and AP1 Coordinate Transcription and Motility. AB - The Tead family transcription factors are the major intracellular mediators of the Hippo-Yap pathway. Despite the importance of Hippo signaling in tumorigenesis, Tead-dependent downstream oncogenic programs and target genes in cancer cells remain poorly understood. Here, we characterize Tead4-mediated transcriptional networks in a diverse range of cancer cells, including neuroblastoma, colorectal, lung, and endometrial carcinomas. By intersecting genome-wide chromatin occupancy analyses of Tead4, JunD, and Fra1/2, we find that Tead4 cooperates with AP1 transcription factors to coordinate target gene transcription. We find that Tead-AP1 interaction is JNK independent but engages the SRC1-3 co-activators to promote downstream transcription. Furthermore, we show that Tead-AP1 cooperation regulates the activity of the Dock-Rac/CDC42 module and drives the expression of a unique core set of target genes, thereby directing cell migration and invasion. Together, our data unveil a critical regulatory mechanism underlying Tead- and AP1-controlled transcriptional and functional outputs in cancer cells. PMID- 26832412 TI - Expression of CD39 on Activated T Cells Impairs their Survival in Older Individuals. AB - In an immune response, CD4(+) T cells expand into effector T cells and then contract to survive as long-lived memory cells. To identify age-associated defects in memory cell formation, we profiled activated CD4(+) T cells and found an increased induction of the ATPase CD39 with age. CD39(+) CD4(+) T cells resembled effector T cells with signs of metabolic stress and high susceptibility to undergo apoptosis. Pharmacological inhibition of ATPase activity dampened effector cell differentiation and improved survival, suggesting that CD39 activity influences T cell fate. Individuals carrying a low-expressing CD39 variant responded better to vaccination with an increase in vaccine-specific memory T cells. Increased inducibility of CD39 after activation may contribute to the impaired vaccine response with age. PMID- 26832413 TI - The Histone Variant MacroH2A1.2 Is Necessary for the Activation of Muscle Enhancers and Recruitment of the Transcription Factor Pbx1. AB - Histone variants complement and integrate histone post-translational modifications in regulating transcription. The histone variant macroH2A1 (mH2A1) is almost three times the size of its canonical H2A counterpart, due to the presence of an ~25 kDa evolutionarily conserved non-histone macro domain. Strikingly, mH2A1 can mediate both gene repression and activation. However, the molecular determinants conferring these alternative functions remain elusive. Here, we report that mH2A1.2 is required for the activation of the myogenic gene regulatory network and muscle cell differentiation. H3K27 acetylation at prospective enhancers is exquisitely sensitive to mH2A1.2, indicating a role of mH2A1.2 in imparting enhancer activation. Both H3K27 acetylation and recruitment of the transcription factor Pbx1 at prospective enhancers are regulated by mH2A1.2. Overall, our findings indicate a role of mH2A1.2 in marking regulatory regions for activation. PMID- 26832414 TI - Condensin Promotes Position Effects within Tandem DNA Repeats via the RITS Complex. AB - Tandem repetitive DNA is highly abundant in eukaryotic genomes and contributes to transcription control and genome stability. However, how the individual sequences within tandem repeats behave remains largely unknown. Here we develop a collection of fission yeast strains with a reporter gene inserted at different units in a tandem repeat array. We show that, contrary to what is usually assumed, transcriptional silencing and replication timing among the individual repeats differ significantly. RNAi-mediated H3K9 methylation is essential for the silencing position effect. A short hairpin RNA of ura4(+) induces silencing in trans within the tandem array in a position-dependent manner. Importantly, the position effect depends on the condensin subunit, cut3(+). Cut3 promotes the position effect via interaction with the RNA-induced transcriptional silencing (RITS) complex. This study reveals variations in silencing within tandem DNA repeats and provides mechanistic insights into how DNA repeats at the individual level are regulated. PMID- 26832415 TI - Condensin and Hmo1 Mediate a Starvation-Induced Transcriptional Position Effect within the Ribosomal DNA Array. AB - Repetitive DNA arrays are important structural features of eukaryotic genomes that are often heterochromatinized to suppress repeat instability. It is unclear, however, whether all repeats within an array are equally subject to heterochromatin formation and gene silencing. Here, we show that in starving Saccharomyces cerevisiae, silencing of reporter genes within the ribosomal DNA (rDNA) array is less pronounced in outer repeats compared with inner repeats. This position effect is linked to the starvation-induced contraction of the nucleolus. We show that the chromatin regulators condensin and Hmo1 redistribute within the rDNA upon starvation; that Hmo1, like condensin, is required for nucleolar contraction; and that the position effect partially depends on both proteins. Starvation-induced nucleolar contraction and differential desilencing of the outer rDNA repeats may provide a mechanism to activate rDNA-encoded RNAPII transcription units without causing general rDNA instability. PMID- 26832416 TI - SMARCAL1 Resolves Replication Stress at ALT Telomeres. AB - Cancer cells overcome replicative senescence by exploiting mechanisms of telomere elongation, a process often accomplished by reactivation of the enzyme telomerase. However, a subset of cancer cells lack telomerase activity and rely on the alternative lengthening of telomeres (ALT) pathway, a recombination-based mechanism of telomere elongation. Although the mechanisms regulating ALT are not fully defined, chronic replication stress at telomeres might prime these fragile regions for recombination. Here, we demonstrate that the replication stress response protein SMARCAL1 is a critical regulator of ALT activity. SMARCAL1 associates with ALT telomeres to resolve replication stress and ensure telomere stability. In the absence of SMARCAL1, persistently stalled replication forks at ALT telomeres deteriorate into DNA double-strand breaks promoting the formation of chromosome fusions. Our studies not only define a role for SMARCAL1 in ALT telomere maintenance, but also demonstrate that resolution of replication stress is a crucial step in the ALT mechanism. PMID- 26832417 TI - TRIP13 Regulates Both the Activation and Inactivation of the Spindle-Assembly Checkpoint. AB - Biochemical studies have indicated that p31(comet) and TRIP13 are critical for inactivating MAD2. To address unequivocally whether p31(comet) and TRIP13 are required for mitotic exit at the cellular level, their genes were ablated either individually or together in human cells. Neither p31(comet) nor TRIP13 were absolutely required for unperturbed mitosis. MAD2 inactivation was only partially impaired in p31(comet)-deficient cells. In contrast, TRIP13-deficient cells contained MAD2 exclusively in the C-MAD2 conformation. Our results indicate that although p31(comet) enhanced TRIP13-mediated MAD2 conversion, it was not absolutely necessary for the process. Paradoxically, TRIP13-deficient cells were unable to activate the spindle-assembly checkpoint, revealing that cells lacking the ability to inactivate MAD2 were incapable in mounting a checkpoint response. These results establish a paradigm of the roles of p31(comet) and TRIP13 in both checkpoint activation and inactivation. PMID- 26832418 TI - Epigenomic Co-localization and Co-evolution Reveal a Key Role for 5hmC as a Communication Hub in the Chromatin Network of ESCs. AB - Epigenetic communication through histone and cytosine modifications is essential for gene regulation and cell identity. Here, we propose a framework that is based on a chromatin communication model to get insight on the function of epigenetic modifications in ESCs. The epigenetic communication network was inferred from genome-wide location data plus extensive manual annotation. Notably, we found that 5-hydroxymethylcytosine (5hmC) is the most-influential hub of this network, connecting DNA demethylation to nucleosome remodeling complexes and to key transcription factors of pluripotency. Moreover, an evolutionary analysis revealed a central role of 5hmC in the co-evolution of chromatin-related proteins. Further analysis of regions where 5hmC co-localizes with specific interactors shows that each interaction points to chromatin remodeling, stemness, differentiation, or metabolism. Our results highlight the importance of cytosine modifications in the epigenetic communication of ESCs. PMID- 26832419 TI - Hierarchical Oct4 Binding in Concert with Primed Epigenetic Rearrangements during Somatic Cell Reprogramming. AB - The core pluripotency factor Oct4 plays key roles in somatic cell reprogramming through transcriptional control. Here, we profile Oct4 occupancy, epigenetic changes, and gene expression in reprogramming. We find that Oct4 binds in a hierarchical manner to target sites with primed epigenetic modifications. Oct4 binding is temporally continuous and seldom switches between bound and unbound. Oct4 occupancy in most of promoters is maintained throughout the entire reprogramming process. In contrast, somatic cell-specific enhancers are silenced in the early and intermediate stages, whereas stem cell-specific enhancers are activated in the late stage in parallel with cell fate transition. Both epigenetic remodeling and Oct4 binding contribute to the hyperdynamic enhancer signature transitions. The hierarchical Oct4 bindings are associated with distinct functional themes at different stages. Collectively, our results provide a comprehensive molecular roadmap of Oct4 binding in concert with epigenetic rearrangements and rich resources for future reprogramming studies. PMID- 26832420 TI - [Tyrosine kinase inhibiting the VEGF pathway and elderly people: Tolerance, pre treatment assessment and side effects management]. AB - Angiogenesis inhibition is a major antitumor strategy that has emerged during the last decade. Oral tyrosine kinase inhibitors (TKI) targeting the VEGF receptor, including sunitinib, sorafenib, axitinib, regorafenib, pazopanib, and vandetanib reduce tumor growth and metastasis. These agents are approved for the treatment of metastatic diseases in first or second-line. They display a narrow therapeutic index. However, data in the elderly and/or in patients with multiple illnesses remain scarce. This population is classically excluded from clinical trials. The aim of this review is to provide an overview of existing literature regarding antiangiogenic TKI tolerance in the elderly (>70 years old). We also highlight key points of the pre-therapeutic evaluation and summarize the management of common toxicities. PMID- 26832421 TI - [Impact of driving restrictions disclosure on quality of life of patients with a glial tumor: A prospective study]. AB - INTRODUCTION: Disclosure of driving restrictions on patients with glial tumors is a complex and difficult task. The difficulty of such task lies in the moral and ethical conflicts it generates for the patient on one hand and caregivers on the other. These aforementioned conflicts impinge upon the patient's quality of life which is one of the important aspects of neuro-oncologic care. PATIENTS AND METHOD: In a prospective survey of 31 patients diagnosed with glial tumors, we studied how the patient perceived the disclosure of driving restrictions specifically the amount of retained information, and the level of distress. RESULTS: It seems that patients fail to assess the juridical implications of driving restrictions. The impact on quality of life as well as psychological and social aspects of these restrictions must not be taken lightly especially in young patients with low-grade glioma who has a long life expectancy. CONCLUSION: Therefore, we believe that planning a specific psychological and social accompaniment of the patient in relation to driving restrictions is an undeniable necessity. PMID- 26832422 TI - [Biosimilar drugs in oncology]. AB - Biosimilar drugs are biologic drugs clinically similar to the reference products. They correspond to a generic approach applied to biologic agents. Biosimilars are aimed to provide cheaper drugs by enhancing the concurrency. The approval of biosimilars is abbreviated when compared to that of the reference biologics but includes clinical trials (distinguishing them from the generics). Current available biosimilars in oncology are filgrastim and epoietin alpha. In the next future, will be launched rituximab and trastuzumab. In France, the development of biosimilars is faced with many hurdles that necessitates a better information of physicians and a greater price discount in the out-patient setting. More globally, harmonisation of recommendations particularly concerning extrapolation of indications and nomenclature are needed for a better acceptance. PMID- 26832423 TI - Two distinct types of remapping in primate cortical area V4. AB - Visual neurons typically receive information from a limited portion of the retina, and such receptive fields are a key organizing principle for much of visual cortex. At the same time, there is strong evidence that receptive fields transiently shift around the time of saccades. The nature of the shift is controversial: Previous studies have found shifts consistent with a role for perceptual constancy; other studies suggest a role in the allocation of spatial attention. Here we present evidence that both the previously documented functions exist in individual neurons in primate cortical area V4. Remapping associated with perceptual constancy occurs for saccades in all directions, while attentional shifts mainly occur for neurons with receptive fields in the same hemifield as the saccade end point. The latter are relatively sluggish and can be observed even during saccade planning. Overall these results suggest a complex interplay of visual and extraretinal influences during the execution of saccades. PMID- 26832424 TI - pH-Responsive reversible self-assembly of gold nanoparticles into nanovesicles. AB - A novel system was reported to realize the reversible self-assembly and disassembly of Au nanovesicles (NVs) driven by pH stimuli with commercially available organic molecules, 4-mercaptobenzonic acid (4-MBA) and oleylamine (OL). Through adjusting deprotonation and protonation of 4-MBA, Au NVs demonstrated a good reversible self-assembly behavior. As a proof-of-concept, Rhodamine B was loaded into the vesicles to demonstrate the reversible pH-responsive controlled release. PMID- 26832425 TI - Sesquiterpenoids and tirucallane triterpenoids from the roots of Scorzonera divaricata. AB - A sulfated guaiane sesquiterpene lactone, an unusual pyridinium alkaloid with a sulfated guaiane sesquiterpene lactone nucleus, an amino conjugate of a sulfated guaiane sesquiterpene lactone, a bisabolane sesquiterpene, three tirucallane triterpenes, and six known compounds, were isolated from roots of Scorzonera divaricata. Their structures and absolute configurations were established based on chemical and spectroscopic methods, X-ray single crystal crystallography, and also by comparison with experimental and calculated ECD spectra. One of the tirucallane triterpenes exhibited significant cytotoxic activities against four human cancer cell lines (HL60, HeLa, HepG2, and SMMC-7721) in vitro. Two of sulfated guaiane sesquiterpenoids also exhibited antioxidant activities by scavenging ABTS cation free radicals. Tirucallane-type and dammarane-type triterpenes were not previously known in the genus Scorzonera. The study suggests that sulfated guaiane-type sesquiterpenoids are a valuable marker for systematic chemical studies in the Lactuceae tribe of the Asteraceae. PMID- 26832426 TI - Return to work after knee replacement: a qualitative study of patient experiences. AB - OBJECTIVE: An increasing number of patients in the working population are undergoing total knee replacement (TKR) for end-stage osteoarthritis. The timing and success of return to work is becoming increasingly important for this group of patients with social and economic implications for patients, employers and society. There is limited understanding of the patient variables that determine the ability to return to work. Our objective was (from the patient's perspective) to gain an insight into the factors influencing return to work following knee replacement. SETTING AND PARTICIPANTS: This qualitative study was undertaken in a secondary-care setting in a large teaching hospital in the north of England. Semistructured interviews were carried out with 10 patients regarding their experiences of returning to work following TKR. OUTCOMES: Interviews were transcribed and analysed using a qualitative thematic approach to identify the factors influencing return to work from the patient's perspective. RESULTS: Three themes were identified that influenced the process of return to work, from the patient's perspective. These were delays in surgical intervention, limited and often inconsistent advice from healthcare professionals regarding return to work, and finally the absence of rehabilitation to optimise patient's recovery and facilitate return to work. CONCLUSIONS: There is currently no consistent process to optimise return to work for patients of working age after TKR. The impact of delayed surgical intervention, limited advice regarding return to work, and a lack of work-focused rehabilitation, all contribute to potential delays in successful return to work. There is a need to change the focus of healthcare provision for this cohort of patients, and provide a tailored healthcare intervention to optimise patient outcomes. PMID- 26832427 TI - Supporting breastfeeding In Local Communities (SILC) in Victoria, Australia: a cluster randomised controlled trial. AB - OBJECTIVES: Breastfeeding has significant health benefits for mothers and infants. Despite recommendations from the WHO, by 6 months of age 40% of Australian infants are receiving no breast milk. Increased early postpartum breastfeeding support may improve breastfeeding maintenance. 2 community-based interventions to increase breastfeeding duration in local government areas (LGAs) in Victoria, Australia, were implemented and evaluated. DESIGN: 3-arm cluster randomised trial. SETTING: LGAs in Victoria, Australia. PARTICIPANTS: LGAs across Victoria with breastfeeding initiation rates below the state average and > 450 births/year were eligible for inclusion. The LGA was the unit of randomisation, and maternal and child health centres in the LGAs comprised the clusters. INTERVENTIONS: Early home-based breastfeeding support by a maternal and child health nurse (home visit, HV) with or without access to a community-based breastfeeding drop-in centre (HV+drop-in). MAIN OUTCOME MEASURES: The proportion of infants receiving 'any' breast milk at 3, 4 and 6 months (women's self report). FINDINGS: 4 LGAs were randomised to the comparison arm and provided usual care (n=41 clusters; n=2414 women); 3 to HV (n=32 clusters; n=2281 women); and 3 to HV+drop-in (n=26 clusters; 2344 women). There was no difference in breastfeeding at 4 months in either HV (adjusted OR 1.04; 95% CI 0.84 to 1.29) or HV+drop-in (adjusted OR 0.92; 95% CI 0.78 to 1.08) compared with the comparison arm, no difference at 3 or 6 months, nor in any LGA in breastfeeding before and after the intervention. Some issues were experienced with intervention protocol fidelity. CONCLUSIONS: Early home-based and community-based support proved difficult to implement. Interventions to increase breastfeeding in complex community settings require sufficient time and partnership building for successful implementation. We cannot conclude that additional community-based support is ineffective in improving breastfeeding maintenance given the level of adherence to the planned protocol. TRIAL REGISTRATION NUMBER: ACTRN12611000898954; Results. PMID- 26832428 TI - Randomised controlled trial of topical kanuka honey for the treatment of acne. AB - OBJECTIVE: To investigate the efficacy of Honevo, a topical 90% medical-grade kanuka honey, and 10% glycerine (honey product) as a treatment for facial acne. DESIGN: Randomised controlled trial with single blind assessment of primary outcome variable. SETTING: Outpatient primary care from 3 New Zealand localities. PARTICIPANTS: Of 136 participants aged between 16 and 40 years with a diagnosis of acne and baseline Investigator's Global Assessment (IGA) for acne score of >= 2.68, participants were randomised to each treatment arm. INTERVENTIONS: All participants applied Protex, a triclocarban-based antibacterial soap twice daily for 12 weeks. Participants randomised to the honey product treatment arm applied this directly after washing off the antibacterial soap, twice daily for 12 weeks. OUTCOME MEASURES: The primary outcome was >= 2 point decrease in IGA score from baseline at 12 weeks. Secondary outcomes included mean lesion counts and changes in subject-rated acne improvement and severity at weeks 4 and 12, and withdrawals for worsening acne. RESULTS: 4/53 (7.6%) participants in the honey product group and 1/53 (1.9%) of participants in the control group had a >= 2 improvement in IGA score at week 12, compared with baseline, OR (95% CI) for improvement 4.2 (0.5 to 39.3), p=0.17. There were 15 and 14 participants who withdrew from the honey product group and control group, respectively. CONCLUSIONS: This randomised controlled trial did not find evidence that addition of medical-grade kanuka honey in combination with 10% glycerine to standard antibacterial soap treatment is more effective than the use of antibacterial soap alone in the treatment of acne. TRIAL REGISTRATION NUMBER: ACTRN12614000003673; Results. PMID- 26832429 TI - Association of chronic insomnia symptoms and recurrent extreme sleep duration over 10 years with well-being in older adults: a cohort study. AB - OBJECTIVES: The extent to which aspects of sleep affect well-being in the long term remains unclear. This longitudinal study examines the association between chronic insomnia symptoms, recurrent sleep duration and well-being at older ages. SETTING: A prospective cohort of UK civil servants (the Whitehall II study). PARTICIPANTS: 4491 women and men (25.2% women) with sleep measured 3 times over 10 years and well-being once at age 55-79 years. Insomnia symptoms and sleep duration were assessed through self-reports in 1997-1999, 2003-2004 and 2007 2009. PRIMARY OUTCOME MEASURES: Indicators of well-being, measured in 2007-2009, were the Control, Autonomy, Self-realisation and Pleasure measure (CASP-19) of overall well-being (range 0-57) and the physical and mental well-being component scores (range 0-100) of the Short Form Health Survey (SF-36). RESULTS: In maximally adjusted analyses, chronic insomnia symptoms were associated with poorer overall well-being (difference between insomnia at 3 assessments vs none 7.0 (SE=0.4) p<0.001), mental well-being (difference -6.9 (SE=0.4), p<0.001) and physical well-being (difference -2.8 (SE=0.4), p<0.001) independently of the other sleep measures. There was a suggestion of a dose-response pattern in these associations. In addition, recurrent short sleep (difference between <= 5 h sleep reported at 3 assessments vs none -1.7 (SE=0.7), p<0.05) and recurrent long sleep (difference between >9 h reported at 2 or 3 assessments vs none -3.5 (SE=0.9), p<0.001) were associated with poorer physical well-being. CONCLUSIONS: We conclude that in older people, chronic insomnia symptoms are negatively associated with all aspects of well-being, whereas recurrent long and short sleep is only associated with reduced physical well-being. PMID- 26832430 TI - A multinational cross-sectional survey of the management of patient medication adherence by European healthcare professionals. AB - OBJECTIVES: To examine which interventions healthcare professionals use to support patients with taking medicines and their perceptions about the effectiveness of those actions. DESIGN: Cross-sectional multinational study. SETTING: Online survey in Austria, Belgium, England, France, Germany, Hungary, The Netherlands, Poland, Portugal and Switzerland. PARTICIPANTS: A total of 3196 healthcare professionals comprising doctors (855), nurses (1047) and pharmacists (1294) currently registered and practising in primary care and community settings. MAIN OUTCOME MEASURES: PRIMARY OUTCOME: Responses to the question 'I ask patients if they have missed any doses of their medication' for each profession and in each country.Secondary outcome: Responses to 50 items concerning healthcare professional behaviour to support patients with medication taking for each profession and in each country. RESULTS: Approximately half of the healthcare professionals in the survey ask patients with long-term conditions whether they have missed any doses of their medication on a regular basis. Pharmacists persistently report that they intervene less than the other two professions to support patients with medicines. No country effects were found for the primary outcome. CONCLUSIONS: Healthcare professionals in Europe are limited in the extent to which they intervene to assist patients having long-term conditions with medication adherence. This represents a missed opportunity to support people with prescribed treatment. These conclusions are based on the largest international survey to date of healthcare professionals' management of medication adherence. PMID- 26832431 TI - Does abortion increase women's risk for post-traumatic stress? Findings from a prospective longitudinal cohort study. AB - OBJECTIVE: To prospectively assess women's risk for post-traumatic stress disorder (PTSD) and of experiencing post-traumatic stress symptoms (PTSS) over 4 ears after seeking an abortion, and to assess whether symptoms are attributed to the pregnancy, abortion or birth, or other events in women's lives. DESIGN: Prospective longitudinal cohort study which followed women from approximately 1 week after receiving or being denied an abortion (baseline), then every 6 months for 4 years (9 interview waves). SETTING: 30 abortion facilities located throughout the USA. PARTICIPANTS: Among 956 women presenting for abortion care, some of whom received an abortion and some of whom were denied due to advanced gestational age; 863 women are included in the longitudinal analyses. MAIN OUTCOME MEASURES: PTSS and PTSD risk were measured using the Primary Care PTSD Screen (PC-PTSD). Index pregnancy-related PTSS was measured by coding the event(s) described by women as the cause of their symptoms. ANALYSES: We used unadjusted and adjusted logistic mixed-effects regression analyses to assess whether PTSS, PTSD risk and pregnancy-related PTSS trajectories of women obtaining abortions differed from those who were denied one. RESULTS: At baseline, 39% of participants reported any PTSS and 16% reported three or more symptoms. Among women with symptoms 1-week post-abortion seeking (n=338), 30% said their symptoms were due to experiences of sexual, physical or emotional abuse or violence; 20% attributed their symptoms to non-violent relationship issues; and 19% said they were due to the index pregnancy. Baseline levels of PTSS, PTSD risk and pregnancy-related PTSS outcomes did not differ significantly between women who received and women who were denied an abortion. PTSS, PTSD risk and pregnancy-related PTSS declined over time for all study groups. CONCLUSIONS: Women who received an abortion were at no higher risk of PTSD than women denied an abortion. PMID- 26832432 TI - Secular trends in smoking during pregnancy according to income and ethnic group: four population-based perinatal surveys in a Brazilian city. AB - OBJECTIVES: To assess socioeconomic and ethnic inequalities in smoking during pregnancy over three decades (1982-2011). SETTING: Population-based study in Pelotas City, Brazil. PARTICIPANTS: All urban women giving birth in the city hospitals in 1982 (5909), 1993 (5223) and 2004 (4201), plus all urban and rural women delivering from January 2011 to April 2012 (6275). PRIMARY OUTCOME: Self reported smoking during pregnancy. RESULTS: The prevalence of smoking during pregnancy fell from 35.7% in 1982 to 21.0% in 2011. In each survey, prevalence decreased with increasing income (p<0.001). In the poorest quintile, smoking fell by 27.4% in the period studied compared to 67.1% in the wealthiest quintile. In all surveys, prevalence was lower among white women than among those who classified themselves as black or brown (p<0.001). Over time, smoking declined by 50.0% among the former and 30.7% among the latter. Absolute and relative inequalities both increased over time. CONCLUSIONS: The reduction in smoking during pregnancy was primarily due to a decline among white, high-income women. Further efforts are needed to reduce smoking among all population groups. PMID- 26832433 TI - Preferences for engagement in health technology assessment decision-making: a nominal group technique with members of the public. AB - OBJECTIVE: To identify characteristics (factors) about health technology assessment (HTA) decisions that are important to the public in determining whether public engagement should be undertaken and the reasons for these choices. DESIGN: Focus groups using a nominal group technique to identify and rank factors relevant to public engagement in HTA decision-making. Thematic analysis was also undertaken to describe reasons underpinning participants' choices and rankings. SETTING: Members of the Australian general public. PARTICIPANTS: 58 people, aged 19-71 years participated in 6 focus groups. RESULTS: 24 factors were identified by participants that were considered important in determining whether public engagement should be undertaken. These factors were individually ranked and grouped into 4 themes to interpret preferences for engagement. Members of the public were more likely to think public engagement was needed when trade-offs between benefits and costs were required to determine 'value', uncertainties in the evidence were present, and family members and/or carers were impacted. The role of public engagement was also seen as important if the existent system lacked transparency and did not provide a voice for patients, particularly for conditions less known in the community. CONCLUSIONS: Members of the public considered value, impact, uncertainty, equity and transparency in determining when engagement should be undertaken. This indicates that the public's preferences on when to undertake engagement relate to both the content of the HTA itself as well as the processes in place to support HTA decision-making. By understanding these preferences, decision-makers can work towards more effective, meaningful public engagement by involving the public in issues that are important to them and/or improving the processes around decision-making. PMID- 26832434 TI - Does T wave inversion in lead aVL predict mid-segment left anterior descending lesions in acute coronary syndrome? A retrospective study. AB - OBJECTIVES: Limited data are available regarding the predictive value of electrocardiographic T wave inversion in lead aVL for mid-segment left anterior descending (MLAD) lesions among patients with acute coronary syndrome (ACS). SETTING: Retrospective single-centre study, using a prospectively-collected coronary angiography database from January 2012 to December 2013. PARTICIPANTS: We included consecutive adult patients with ACS who underwent urgent percutaneous coronary intervention (PCI) within 24 h after arriving at the hospital. We excluded patients who did not undergo an ECG before PCI, patients with proximal MLAD occlusion and patients diagnosed with vasospastic angina. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was MLAD lesion >50%. The other outcome of interest was MLAD lesion as a cause of ACS. First, we evaluated the diagnostic values of T wave inversion in lead aVL regardless of other T wave changes for each outcome. Second, we evaluated the diagnostic values of isolated T wave inversion in lead aVL. RESULTS: Overall, 219 patients were eligible for the analysis. T wave inversion in lead aVL regardless of other T wave changes had a sensitivity of 32.9%, specificity of 48.2%, positive predictive value of 27.6% and negative predictive value of 54.5% for predicting MLAD lesions. Isolated T wave inversion in lead aVL had a sensitivity of 9.8%, specificity of 86.9%, positive predictive value of 30.8% and negative predictive value of 61.7% for predicting MLAD lesions. These diagnostic values did not change materially when focusing on patients with MLAD lesion as the cause. CONCLUSIONS: While T wave inversion in lead aVL regardless of other T wave changes had low diagnostic values for predicting MLAD lesions, isolated T wave inversion in lead aVL had a high specificity. Our inferences underscore the importance of a cautious interpretation of T wave inversion in lead aVL among patients with ACS. PMID- 26832435 TI - ADding negative pRESSure to improve healING (the DRESSING trial): a RCT protocol. AB - INTRODUCTION: Obese women are more likely to develop a surgical site infection (SSI) following caesarean section (CS) than non-obese women. Negative pressure wound therapy (NPWT) is increasingly being used to reduce SSI with limited evidence for its effectiveness. OBJECTIVES: To determine the clinical and cost effectiveness of using NPWT in obese women having elective and semiurgent CS. METHODS AND ANALYSIS: A multisite, superiority parallel pragmatic randomised controlled trial with an economic evaluation. Women with a body mass index (BMI) of >= 30, booked for elective and semiurgent CS at 4 Australian acute care hospitals will be targeted. A total of 2090 women will be enrolled. A centralised randomisation service will be used with participants block randomised to either NPWT or standard surgical dressings in a 1:1 ratio, stratified by hospital. The primary outcome is SSI; secondary outcomes include type of SSI, length of stay, readmission, wound complications and health-related quality of life. Economic outcomes include direct healthcare costs and cost-effectiveness, which will be evaluated using incremental cost per quality-adjusted life year gained. Data will be collected at baseline, and participants followed up on the second postoperative day and weekly from the day of surgery for 4 weeks. Outcome assessors will be masked to allocation. The primary statistical analysis will be based on intention-to-treat. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the ethics committees of the participating hospitals and universities. The findings of the trial will be disseminated through peer reviewed journals, national and international conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12615000286549; Pre-results. PMID- 26832436 TI - A Multicenter Prospective Study to Investigate the Diagnostic Accuracy of the SeHCAT Test in Measuring Bile Acid Malabsorption: Research Protocol. AB - BACKGROUND: Bile acid malabsorption (BAM) is one possible explanation for chronic diarrhea. BAM may be idiopathic, or result from ileal resection or inflammation including Crohn's disease, or may be secondary to other conditions, including cholecystectomy, peptic ulcer surgery, and chronic pancreatitis. No "gold standard" exists for clinical diagnosis of BAM, but response to treatment with a bile acid sequestrant (BAS) is often accepted as confirmation. The SeHCAT (tauroselcholic [selenium-75] acid) test uses a radiolabeled synthetic bile acid and provides a diagnostic test for BAM, but its performance against "trial of treatment" is unknown. Fibroblast growth factor 19 (FGF-19) and 7-alpha-hydroxy-4 cholesten-3-one (C4) also offer potential new biomarkers of BAM. OBJECTIVE: This protocol describes a multicenter prospective study to evaluate the diagnostic accuracy of SeHCAT and 2 biomarkers in predicting BAM as assessed by trial of treatment. METHODS: Participating gastroenterology centers should have a minimum workload of 30 SeHCAT patients per annum. Patients should not be pregnant, on medication that could confound follow-up, or have any severe comorbidity. All eligible patients attending a gastrointestinal appointment will be invited to participate. On attending the SeHCAT test, blood and fecal samples will be collected for analysis of FGF-19 by enzyme-linked immunosorbent assay and for C4 and fractionated bile acids by liquid chromatography-mass spectrometry. A capsule containing radiolabeled SeHCAT will be administered orally and a scan performed to measure SeHCAT activity. Patients will return on day 7 to undergo a second scan to measure percentage SeHCAT retention. The test result will be concealed from clinicians and patients. BAS will be dispensed to all patients, with a follow-up gastroenterologist appointment at 2 weeks for clinical assessment of treatment response and adherence. Patients responding positively will continue treatment for a further 2 weeks and all patients will have a final follow-up at 8 weeks. The diagnostic accuracy of the SeHCAT test and biomarkers will be analyzed at different thresholds using sensitivity, specificity, positive and negative predictive value, likelihood ratios, and area under the curve in a sample of 600 patients. Multivariable logistic regression models will be used to assess the association between presence of BAM and continuous SeHCAT retention levels after adjustment for confounders. RESULTS: Funding is being sought to conduct this research. CONCLUSIONS: The SeHCAT test for diagnosis of BAM has been in common use in the United Kingdom for more than 30 years and an evidence-based assessment of its accuracy is overdue. The proposed study has some challenges. Some forms of BAS treatment are unpleasant due to the texture and taste of the resin powder, which may negatively affect recruitment and treatment adherence. Trial of treatment is not as "golden" a standard as would be ideal, and itself warrants further study. PMID- 26832437 TI - Apomixis Allows the Transgenerational Fixation of Phenotypes in Hybrid Plants. AB - The introduction of apomixis-asexual reproduction through seeds-into crop plants is considered the holy grail of agriculture, as it would provide a mechanism to maintain agriculturally important phenotypes [1, 2]. Apomicts produce clonal offspring, such that apomixis could be used to transgenerationally fix any genotype, including that of F1 hybrids, which are used in agriculture due to their superior vigor and yield [3-9]. However, traits (phenotypes) do not only result from a complex combination of genetic and environmental variation but can also be influenced by epigenetic variation, which can be transgenerationally heritable in plants [10-15]. Hence, it is far from clear whether genetic fixation by apomixis suffices to fix the agriculturally relevant phenotypes of F1 hybrids, in particular because hybridization was recently shown to induce epigenetic changes [16, 17]. Here, we show that the phenotypes of Hieracium pilosella hybrids can be fixed across generations by apomixis. Using a natural apomict, we created 11 hybrid genotypes (lines). In these and a parental line, we analyzed 20 phenotypic traits that are related to plant growth and reproduction. Of the 20 traits, 18 (90%) were stably inherited over two apomictic generations, grown at the same time in a randomized design, in 11 of the 12 lines. Although one hybrid line showed phenotypic instability, our results provide a fundamental proof of principle, demonstrating that apomixis can indeed be used in plant breeding and seed production to fix complex, quantitative phenotypes across generations. PMID- 26832438 TI - Selective Activation of the Deep Layers of the Human Primary Visual Cortex by Top Down Feedback. AB - In addition to bottom-up input, the visual cortex receives large amounts of feedback from other cortical areas [1-3]. One compelling example of feedback activation of early visual neurons in the absence of bottom-up input occurs during the famous Kanizsa illusion, where a triangular shape is perceived, even in regions of the image where there is no bottom-up visual evidence for it. This illusion increases the firing activity of neurons in the primary visual cortex with a receptive field on the illusory contour [4]. Feedback signals are largely segregated from feedforward signals within each cortical area, with feedforward signals arriving in the middle layer, while top-down feedback avoids the middle layers and predominantly targets deep and superficial layers [1, 2, 5, 6]. Therefore, the feedback-mediated activity increase in V1 during the perception of illusory shapes should lead to a specific laminar activity profile that is distinct from the activity elicited by bottom-up stimulation. Here, we used fMRI at high field (7 T) to empirically test this hypothesis, by probing the cortical response to illusory figures in human V1 at different cortical depths [7-14]. We found that, whereas bottom-up stimulation activated all cortical layers, feedback activity induced by illusory figures led to a selective activation of the deep layers of V1. These results demonstrate the potential for non-invasive recordings of neural activity with laminar specificity in humans and elucidate the role of top-down signals during perceptual processing. PMID- 26832440 TI - Signal Use by Octopuses in Agonistic Interactions. AB - Cephalopods show behavioral parallels to birds and mammals despite considerable evolutionary distance [1, 2]. Many cephalopods produce complex body patterns and visual signals, documented especially in cuttlefish and squid, where they are used both in camouflage and a range of interspecific interactions [1, 3-5]. Octopuses, in contrast, are usually seen as solitary and asocial [6, 7]; their body patterns and color changes have primarily been interpreted as camouflage and anti-predator tactics [8-12], though the familiar view of the solitary octopus faces a growing list of exceptions. Here, we show by field observation that in a shallow-water octopus, Octopus tetricus, a range of visible displays are produced during agonistic interactions, and these displays correlate with the outcome of those interactions. Interactions in which dark body color by an approaching octopus was matched by similar color in the reacting octopus were more likely to escalate to grappling. Darkness in an approaching octopus met by paler color in the reacting octopus accompanied retreat of the paler octopus. Octopuses also displayed on high ground and stood with spread web and elevated mantle, often producing these behaviors in combinations. This study is the first to document the systematic use of signals during agonistic interactions among octopuses. We show prima facie conformity of our results to an influential model of agonistic signaling [13]. These results suggest that interactions have a greater influence on octopus evolution than has been recognized and show the importance of convergent evolution in behavioral traits. PMID- 26832439 TI - Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans. AB - Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology. PMID- 26832441 TI - Rules and Self-Organizing Properties of Post-embryonic Plant Organ Cell Division Patterns. AB - Plants form new organs with patterned tissue organization throughout their lifespan. It is unknown whether this robust post-embryonic organ formation results from stereotypic dynamic processes, in which the arrangement of cells follows rigid rules. Here, we combine modeling with empirical observations of whole-organ development to identify the principles governing lateral root formation in Arabidopsis. Lateral roots derive from a small pool of founder cells in which some take a dominant role as seen by lineage tracing. The first division of the founders is asymmetric, tightly regulated, and determines the formation of a layered structure. Whereas the pattern of subsequent cell divisions is not stereotypic between different samples, it is characterized by a regular switch in division plane orientation. This switch is also necessary for the appearance of patterned layers as a result of the apical growth of the primordium. Our data suggest that lateral root morphogenesis is based on a limited set of rules. They determine cell growth and division orientation. The organ-level coupling of the cell behavior ensures the emergence of the lateral root's characteristic features. We propose that self-organizing, non-deterministic modes of development account for the robustness of plant organ morphogenesis. PMID- 26832442 TI - Hippocampal-Prefrontal Theta Oscillations Support Memory Integration. AB - Integration of separate memories forms the basis of inferential reasoning--an essential cognitive process that enables complex behavior. Considerable evidence suggests that both hippocampus and medial prefrontal cortex (mPFC) play a crucial role in memory integration. Although previous studies indicate that theta oscillations facilitate memory processes, the electrophysiological mechanisms underlying memory integration remain elusive. To bridge this gap, we recorded magnetoencephalography data while participants performed an inference task and employed novel source reconstruction techniques to estimate oscillatory signals from the hippocampus. We found that hippocampal theta power during encoding predicts subsequent memory integration. Moreover, we observed increased theta coherence between hippocampus and mPFC. Our results suggest that integrated memory representations arise through hippocampal theta oscillations, possibly reflecting dynamic switching between encoding and retrieval states, and facilitating communication with mPFC. These findings have important implications for our understanding of memory-based decision making and knowledge acquisition. PMID- 26832443 TI - NuMA Phosphorylation by Aurora-A Orchestrates Spindle Orientation. AB - Spindle positioning is essential for tissue morphogenesis and homeostasis. The signaling network synchronizing spindle placement with mitotic progression relies on timely recruitment at the cell cortex of NuMA:LGN:Galphai complexes, in which NuMA acts as a receptor for the microtubule motor Dynein. To study the implication of Aurora-A in spindle orientation, we developed protocols for the partial inhibition of its activity. Under these conditions, in metaphase NuMA and Dynein accumulate abnormally at the spindle poles and do not reach the cortex, while the cortical distribution of LGN remains unperturbed. FRAP experiments revealed that Aurora-A governs the dynamic exchange between the cytoplasmic and the spindle pole-localized pools of NuMA. We show that Aurora-A phosphorylates directly the C terminus of NuMA on three Ser residues, of which Ser1969 determines the dynamic behavior and the spindle orientation functions of NuMA. Most interestingly, we identify a new microtubule-binding domain of NuMA, which does not overlap with the LGN-binding motif. Our study demonstrates that in metaphase the direct phosphorylation of NuMA by Aurora-A controls its cortical enrichment, and that this is the major event underlying the spindle orientation functions of Aurora-A in transformed and non-transformed cells in culture. Phosphorylation of NuMA by Aurora-A does not affect its affinity for microtubules or for LGN but rather determines the mobility of the protein at the spindle poles. The finding that NuMA can associate concomitantly with LGN and microtubules suggests that its microtubule-binding activity contributes to anchor Dynein-loaded microtubule +TIPs at cortical sites with LGN. PMID- 26832444 TI - Motor Skills Are Strengthened through Reconsolidation. AB - Newly acquired motor skills become stabilized through consolidation [1]. However, we know from daily life that consolidated skills are modified over multiple bouts of practice and in response to newfound challenges [2]. Recent evidence has shown that memories can be modified through reconsolidation, in which previously consolidated memories can re-enter a temporary state of instability through retrieval, and in order to persist, undergo re-stabilization [3-8]. Although observed in other memory domains [5, 6], it is unknown whether reconsolidation leads to strengthened motor skills over multiple episodes of practice. Using a novel intervention after the retrieval of a consolidated skill, we found that skill can be modified and enhanced through exposure to increased sensorimotor variability. This improvement was greatest in those participants who could rapidly adjust their sensorimotor output in response to the relatively large fluctuations presented during the intervention. Importantly, strengthening required the reactivation of the consolidated skill and time for changes to reconsolidate. These results provide a key demonstration that consolidated motor skills continue to change as needed through the remapping of motor command to action goal, with strong implications for rehabilitation. PMID- 26832445 TI - Confinement Correction to Mercury Intrusion Capillary Pressure of Shale Nanopores. AB - We optimized potential parameters in a molecular dynamics model to reproduce the experimental contact angle of a macroscopic mercury droplet on graphite. With the tuned potential, we studied the effects of pore size, geometry, and temperature on the wetting of mercury droplets confined in organic-rich shale nanopores. The contact angle of mercury in a circular pore increases exponentially as pore size decreases. In conjunction with the curvature-dependent surface tension of liquid droplets predicted from a theoretical model, we proposed a technique to correct the common interpretation procedure of mercury intrusion capillary pressure (MICP) measurement for nanoporous material such as shale. Considering the variation of contact angle and surface tension with pore size improves the agreement between MICP and adsorption-derived pore size distribution, especially for pores having a radius smaller than 5 nm. The relative error produced in ignoring these effects could be as high as 44%--samples that contain smaller pores deviate more. We also explored the impacts of pore size and temperature on the surface tension and contact angle of water/vapor and oil/gas systems, by which the capillary pressure of water/oil/gas in shale can be obtained from MICP. This information is fundamental to understanding multiphase flow behavior in shale systems. PMID- 26832446 TI - Using synthetic bacterial enhancers to reveal a looping-based mechanism for quenching-like repression. AB - We explore a model for 'quenching-like' repression by studying synthetic bacterial enhancers, each characterized by a different binding site architecture. To do so, we take a three-pronged approach: first, we compute the probability that a protein-bound dsDNA molecule will loop. Second, we use hundreds of synthetic enhancers to test the model's predictions in bacteria. Finally, we verify the mechanism bioinformatically in native genomes. Here we show that excluded volume effects generated by DNA-bound proteins can generate substantial quenching. Moreover, the type and extent of the regulatory effect depend strongly on the relative arrangement of the binding sites. The implications of these results are that enhancers should be insensitive to 10-11 bp insertions or deletions (INDELs) and sensitive to 5-6 bp INDELs. We test this prediction on 61 sigma(54)-regulated qrr genes from the Vibrio genus and confirm the tolerance of these enhancers' sequences to the DNA's helical repeat. PMID- 26832447 TI - Author Reply. PMID- 26832448 TI - Editorial Comment. PMID- 26832449 TI - Photoselective Vaporization of the Prostate vs Plasmakinetic Resection of the Prostate: A Randomized Prospective Trial With 12-Month Follow-up in Mainland China. AB - OBJECTIVE: To compare the short-term efficacy and safety results of photoselective vaporization of the prostate (PVP) and plasmakinetic resection of prostate (PKRP), 2 methods of treating benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS) in mainland China. METHODS: One hundred twenty patients with LUTS secondary to BPH were randomly divided into 2 groups: PVP group (n = 61) and PKRP group (n = 59). Perioperative data and postoperative complications were recorded for both groups. Patients were followed up for 12 months after treatment. RESULTS: Compared with PKRP, PVP required a longer operation time (56 vs 41 minutes; P <.01). PVP also needed shorter catheterization time (2.4 vs 3.5 days; P <.01) and shorter length of hospitalization (3.5 vs 5.1 days; P <.01). International Prostate Symptom Score, Qmax, and quality of life score were significantly improved for both groups after surgery, and no significant differences were apparent between the 2 groups, for up to 12 months. Short-term complications were assessed in regard to necessity of blood transfusion (1 vs 1), clot retention (1 vs 0), reoperation (1 vs 0), incontinence (0 vs 0), urethral stricture (1 vs 0), and retrograde ejaculation (4 vs 6) in the PVP vs PKRP groups, respectively. CONCLUSION: In patients with BPH related LUTS, PVP may be a superior treatment to PKRP as it relates to the endpoints of this study, with short-term results after a 12-month follow-up as length of hospital stay and catheterization time needed were both less than what was required for PKRP. Long-term comparative data are required to clearly define the role of PVP and PKRP in patients. PMID- 26832450 TI - Lung cancer screening: utility of molecular applications in conjunction with low dose computed tomography guidelines. AB - Finding early-stage lung cancer where there is a higher chance for patient survival remains a major healthcare challenge. Low-dose spiral computed tomography for high-risk patients can increase the detection of cancers with certain tradeoffs, such as increased radiation exposure and surgical risks for false-positive cases. New molecular markers and assays show considerable promise to further reduce healthcare costs and improve lung cancer survival rates but require further validation. This review summarizes and discusses the current state of research in lung cancer screening and highlights developments in biomarker research for lung cancer diagnostics. PMID- 26832451 TI - Does self-affirmation following ego depletion moderate restrained eaters' explicit preferences for, and implicit associations with, high-calorie foods? AB - OBJECTIVE: The difficulty for chronic dieters (i.e. restrained eaters) in regulating their food intake is a conflict between two apparently incompatible goals: eating enjoyment and weight control. The latter goal consistently relies on the deployment of cognitive resources, and very often on a significant amount of self-control. This study investigated whether self-affirmation might counteract the effect of ego depletion on restrained eaters' motivation to consume high-calorie foods. DESIGN: Participants (N = 183) were assigned to one of four conditions in a 2 * 2 (Ego depletion * Self-Affirmation) experimental design and were subsequently exposed to images of high- and low-calorie foods. MAIN OUTCOME MEASURES: Participants completed tasks assessing their implicit and explicit preferences for high vs. low-calorie foods, along with a measure of the perceived self-control required to resist foods. RESULTS: Results indicated that, following ego depletion, self-affirmation facilitated restrained eaters' perceptions of self-control and led to lower explicit preferences for high calorie foods. This pattern was not apparent for implicit preferences. CONCLUSION: Self-affirmation interventions may be capable of restoring self control resources among restrained eaters. Pointers for future research and practical applications are discussed. PMID- 26832452 TI - Crude Saponins of Panax notoginseng Have Neuroprotective Effects To Inhibit Palmitate-Triggered Endoplasmic Reticulum Stress-Associated Apoptosis and Loss of Postsynaptic Proteins in Staurosporine Differentiated RGC-5 Retinal Ganglion Cells. AB - Increased apoptosis of retinal ganglion cells (RGCs) contributes to the gradual loss of retinal neurons at the early phase of diabetic retinopathy (DR). There is an urgent need to search for drugs with neuroprotective effects against apoptosis of RGCs for the early treatment of DR. This study aimed to investigate the neuroprotective effects of saponins extracted from Panax notoginseng, a traditional Chinese medicine, on apoptosis of RGCs stimulated by palmitate, a metabolic factor for the development of diabetes and its complications, and to explore the potential molecular mechanism. We showed that crude saponins of P. notoginseng (CSPN) inhibited the increased apoptosis and loss of postsynaptic protein PSD-95 by palmitate in staurosporine-differentiated RGC-5 cells. Moreover, CSPN suppressed palmitate-induced reactive oxygen species generation and endoplasmic reticulum stress-associated eIF2alpha/ATF4/CHOP and caspase 12 pathways. Thus, our findings address the potential therapeutic significance of CSPN for the early stage of DR. PMID- 26832454 TI - Chest wall mechanics before and after diaphragm plication. AB - BACKGROUND: Following diaphragmatic plication for unilateral paralysis, the effect on global chest wall function are unknown. Our hypothesis was that chest wall function would improve in both sides of the chest after plication of the paralysed side. CASE PRESENTATION: Using Optoelectronic Plethysmography, total and regional chest wall volumes were measured in one patient before and after left diaphragmatic plication. Volumes were recorded at quiet breathing. Respiratory capacity improved during quiet breathing when measured before and 6 months after surgery. These improvements occur at the abdominal-rib cage level in both operated and contralateral. Prior to surgery the abdominal rib cage motion was out of phase to the upper rib cage and abdominal compartment in both sides of the chest. Synchrony of all three compartments was restored after plication. CONCLUSION: This physiological study is the first published data in humans to show improvement in chest wall motion both in operated and contralateral side following diaphragmatic plication for unilateral paralysis. PMID- 26832453 TI - Clinical significance of different virus load of human bocavirus in patients with lower respiratory tract infection. AB - To assess the impact of human bocavirus (HBoV) virus load on epidemiologic and clinical characteristics in children with lower respiratory tract infection (LRTI). Clinical records of a total of 654 patients with HBoV infection during January 2013 and December 2014 were retrospectively reviewed. Patients with high HBoV virus load infection had a similar age distribution with the total HBoV infection, which had a peak age group of 6-24 months. Patients with high virus load are significantly younger (P < 0.01) than those with low load. The patients who had wheeze and tachypnea/dyspnea at presentation were more strongly affiliated with the patients with high virus load (both P < 0.01). Co-infection was found significantly more frequently among patients with low virus load than those with high virus load (57.0% vs 38.9%; P < 0.01). High virus load was a significant predictor of severe LRTI (P < 0.05). HBoV infections are found in an important proportion of the hospitalized children with respiratory illnesses (8.85% in our series). A high HBoV virus load could be an etiologic agent for LRTI, which may lead to more severe lower respiratory tract symptom and severe disease. PMID- 26832455 TI - An integrated multi-electrode-optrode array for in vitro optogenetics. AB - Modulation of a group of cells or tissue needs to be very precise in order to exercise effective control over the cell population under investigation. Optogenetic tools have already demonstrated to be of great value in the study of neuronal circuits and in neuromodulation. Ideally, they should permit very accurate resolution, preferably down to the single cell level. Further, to address a spatially distributed sample, independently addressable multiple optical outputs should be present. In current techniques, at least one of these requirements is not fulfilled. In addition to this, it is interesting to directly monitor feedback of the modulation by electrical registration of the activity of the stimulated cells. Here, we present the fabrication and characterization of a fully integrated silicon-based multi-electrode-optrode array (MEOA) for in vitro optogenetics. We demonstrate that this device allows for artifact-free electrical recording. Moreover, the MEOA was used to reliably elicit spiking activity from ChR2-transduced neurons. Thanks to the single cell resolution stimulation capability, we could determine spatial and temporal activation patterns and spike latencies of the neuronal network. This integrated approach to multi-site combined optical stimulation and electrical recording significantly advances today's tool set for neuroscientists in their search to unravel neuronal network dynamics. PMID- 26832456 TI - Children With Special Health Care Needs: Child Health and Functioning Outcomes and Health Care Service Use. AB - This study describes health, functioning, and health care service use by medically complex technology-dependent children according to condition severity (moderately disabled, severely disabled, and vegetative state). Data were collected monthly for 5 months using the Pediatric Quality of Life Generic Core Module 4.0 Parent-Proxy Report. Health care service use measured the number of routine and acute care office visits (including primary and specialty physicians), emergency department visits, hospitalizations, nursing health care services, special therapies, medications, medical technology devices (MTDs), and assistive devices. Child physical health was different across the condition severity groups. The average age of the children was 10.1 years (SD, 6.2); the average number of medications used was 5.5 (SD, 3.7); the average number of MTDs used was 4.2 (SD, 2.9); and the average number of assistive devices used was 4.3 (SD, 2.7). Severely disabled and vegetative children were similar in age (older) and had a similar number of medications, MTDs, and assistive devices (greater) than moderately disabled children. The advanced practice nurse care coordinator role is necessary for the health and functioning of medically complex, technology dependent children. PMID- 26832457 TI - Invited review: MnmE, a GTPase that drives a complex tRNA modification reaction. AB - MnmE is a multi-domain GTPase that is conserved from bacteria to man. Together with its partner protein MnmG it is involved in the synthesis of a tRNA wobble uridine modification. The orthologues of these proteins in eukaryotes are targeted to mitochondria and mutations in the encoding genes are associated with severe mitochondrial diseases. While classical small GTP-binding proteins are regulated via auxiliary GEFs and GAPs, the GTPase activity of MnmE is activated via potassium-dependent homodimerization of its G domains. In this review we focus on the catalytic mechanism of GTP hydrolysis by MnmE and the large scale conformational changes that are triggered throughout the GTPase cycle. We also discuss how these conformational changes might be used to drive and tune the complex tRNA modification reaction. (c) 2016 Wiley Periodicals, Inc. Biopolymers 105: 568-579, 2016. PMID- 26832458 TI - Holographic fabrication of large-constant concave gratings for wide-range flat field spectrometers with the addition of a concave lens. AB - We present a new design for the fabrication of concave gratings with large grating constants for flat-field miniature spectrometers with a wide spectral band. In this new design, one of the two optical paths for the holographic lithography of a curved grating structure with variable line spacing is modified by adding a concave lens in front of the point source. The addition of the concave lens allows the real point source, as well as the spatial filter for generating this point source, to be moved back. In this manner, the two spatial filters for generating two point sources are separated. Avoiding the physical conflict between these two spatial filters reduces the difficulty of fabricating large-constant concave gratings. Experimental results verify the feasibility of the proposed design in fabricating concave gratings with large grating constants. The resolution of a spectrometer using the fabricated concave grating is evaluated and found to be better than 1.1 nm across a spectral band ranging from 360 nm to 825 nm. PMID- 26832459 TI - L-band wavelength-tunable dissipative soliton fiber laser. AB - A tunable L-band dissipative soliton (DS) fiber laser with nonlinear polarization rotation (NPR) playing the roles of both a saturable absorber (SA) and a tunable filter has been demonstrated experimentally and numerically. By appropriate adjustment of the states of the polarization controllers (PCs) and the pump power, DSs with continuously tunable wavelengths have been observed over the wavelength range from 1583.0 to 1602.4 nm with a 3-dB spectral bandwidth of around 20 nm and from 1581.9 nm to 1602.6 nm with a 3-dB spectral bandwidth of around 4 nm. In addition, we have observed that by increasing the pump power, the 3-dB spectral bandwidth of the DS could be increased without pulse breaking. Numerical results for the characteristics of the DSs are in accord with the experimental data. PMID- 26832460 TI - Spectral-temporal composition matters when cascading supercontinua into the mid infrared. AB - Supercontinuum generation in chalcogenide fibers is a promising technology for broadband spatially coherent sources in the mid-infrared, but it suffers from discouraging commercial prospects, mainly due to a lack of suitable pump lasers. Here, a promising approach is experimentally demonstrated using an amplified 1.55 MUm diode laser to generate a pump continuum up to 4.4 MUm in cascaded silica and fluoride fibers. We present experimental evidence and numerical simulations confirming that the spectral-temporal composition of the pump continuum is critical for continued broadening in a chalcogenide fiber. The fundamental physical question is concerned with the long-wavelength components of the pump spectrum, which may consist of either solitons or dispersive waves. In demonstrating this we present a commercially viable fiber-cascading configuration to generate a mid-infrared supercontinuum up to 7 MUm in commercial chalcogenide fibers. PMID- 26832461 TI - Understanding light trapping by resonant coupling to guided modes and the importance of the mode profile. AB - We present a simple conceptual model describing the absorption enhancement provided by diffraction gratings due to resonant coupling to guided modes in a multi-layered structure. In doing so, we provide insight into why certain guided modes are more strongly excited than others and demonstrate that the spatial overlap of the mode profile with the grating is important. The model is verified by comparison to optical simulations and experimental measurements. We fabricate metal nanoparticle gratings integrated as back contacts in solution-processed PbS colloidal quantum dot photodiodes. The measured photocurrent at the target wavelength is enhanced by 250%, with reference to planar devices, due to resonant coupling to guided modes with strong spatial overlap with the gratings. In comparison, resonant coupling to weakly overlapping modes results in a 25% increase at the same wavelength. PMID- 26832462 TI - Broadband second-harmonic phase-matching in dispersion engineered slot waveguides. AB - Parametric optical nonlinearities are usually weak and require both high optical field intensity and phase-matching. Micro/nanophotonics, with strong confinement of light in waveguides of nanometer-scale cross-sections, can provide high field intensity, but is still in need of a solution for phase-matching across a broad bandwidth. In this article, we show that mode-coupling in slot waveguides can engineer the waveguide modal dispersion, and with proper choice of materials, can achieve on-chip broadband second-harmonic phase-matching. A phase-matching bandwidth in the range of 220 nm at mid-infrared can occur for a hetero-slot waveguide consisting of aluminum nitride (AlN) and silicon nitride (SiN). With a high-nonlinearity polymer as cladding material, about 1.76 W(-1)cm(-2) of normalized conversion efficiency in second-harmonic-generation (SHG) and about 23 dB signal gain in degenerate optical parametric amplification (DOPA) can be achieved over a broad bandwidth. An asymmetric-slot waveguide configuration and a thermal tuning scheme are proposed to reduce the fabrication difficulty. This concept of broadband second-harmonic phase-matching can be extended to other nonlinear optical frequency mixing processes, thus expanding the scope of on-chip nonlinear optical applications. PMID- 26832463 TI - Daytime sea fog retrieval based on GOCI data: a case study over the Yellow Sea. AB - In this paper, a new daytime sea fog detection algorithm has been developed by using Geostationary Ocean Color Imager (GOCI) data. Based on spectral analysis, differences in spectral characteristics were found over different underlying surfaces, which include land, sea, middle/high level clouds, stratus clouds and sea fog. Statistical analysis showed that the Rrc (412 nm) (Rayleigh Corrected Reflectance) of sea fog pixels is approximately 0.1-0.6. Similarly, various band combinations could be used to separate different surfaces. Therefore, three indices (SLDI, MCDI and BSI) were set to discern land/sea, middle/high level clouds and fog/stratus clouds, respectively, from which it was generally easy to extract fog pixels. The remote sensing algorithm was verified using coastal sounding data, which demonstrated that the algorithm had the ability to detect sea fog. The algorithm was then used to monitor an 8-hour sea fog event and the results were consistent with observational data from buoys data deployed near the Sheyang coast (121 degrees E, 34 degrees N). The goal of this study was to establish a daytime sea fog detection algorithm based on GOCI data, which shows promise for detecting fog separately from stratus. PMID- 26832464 TI - Simultaneous multi-channel absolute position alignment by multi-order grating interferometry. AB - A simultaneous multi-channel absolute position alignment system is investigated to determine the absolute position of a grating mark. By employing a multi-order grating interferometer and a multi-channel phase extraction method, many equivalent measurement results are generated simultaneously for stable and consistent measurement. By combining measurement results of different orders, low order signals enabled large unambiguous measurement ranges, and high-order signals enhanced the measurement accuracy. Comparison experiments performed using an incremental HeNe reference interferometer yielded the standard deviations of smaller than 11.48nm under laboratory conditions. The proposed scheme will enable a new class of absolute position alignment system for industrial applications. PMID- 26832465 TI - Fading-free transmission of 124-Gb/s PDM-DMT signal over 100-km SSMF using digital carrier regeneration. AB - The coherent reception of intensity modulated signal has been recently widely investigated, in which the signal is recovered by the envelop detection. High linewidth tolerance is achieved with such scheme. However, strong optical carrier exists during the transmission, which degrades the optical power efficiency. In this paper, an efficient modulation scheme for discrete multi-tone (DMT) signal is proposed based on the Mach-Zehnder modulator (MZM). Different from the traditional intensity modulation, the proposed method employs both intensity and phase domain. Thus, the optical carrier power can be greatly reduced by adjusting the bias of MZM around the null point. By employing coherent detection and digital carrier regeneration (DCR), the carrier suppressed DMT signal can be recovered using envelop detection. No carrier frequency or phase estimation is required. Numerical investigations are made to demonstrate the feasibility, in which significant improvements are found for the proposed DCR method, showing great tolerance against laser linewidth and carrier power reduction. Finally, a 124-Gb/s transmission of polarization-division multiplexed DMT (PDM-DMT) signal is demonstrated over 100-km SSMF, with only -8 dB optical carrier to signal power ratio (CSPR). PMID- 26832466 TI - Ultra-thin rigid endoscope: two-photon imaging through a graded-index multi-mode fiber. AB - Rigid endoscopes like graded-index (GRIN) lenses are known tools in biological imaging, but it is conceptually difficult to miniaturize them. In this letter, we demonstrate an ultra-thin rigid endoscope with a diameter of only 125 MUm. In addition, we identify a domain where two-photon endoscopic imaging with fs-pulse excitation is possible. We validate the ultra-thin rigid endoscope consisting of a few cm of graded-index multi-mode fiber by using it to acquire optically sectioned two-photon fluorescence endoscopic images of three-dimensional samples. PMID- 26832467 TI - k-dispersion engineering of spoof surface plasmon polaritons for beam steering. AB - In this paper, we propose to achieve beam steering by k-dispersion engineering of spoof surface plasmon polaritons (spoof SPP) at microwave frequencies. The planar plasmonic metamaterials (PPMs) are employed to couple and guide spoof SPP. High efficiency transmission based on spoof SPP coupling is realized via matching the wave-vectors of the spoof SPP and the space wave. The transmission phase can be modulated by k-dispersion engineering of the spoof SPP with great freedom. Due to the independent phase shift produced by the spoof SPP on the PPMs, the phase gradient achieved by using the PPMs as the sub-unit cells can be altered by changing the repetition period of the sub-unit cells. Two phase gradient materials (PGMs) are achieved by using nine different PPMs as the sub-unit cells with the repetition period q = 4mm and 4.5mm. Both the simulated and measured results demonstrated the excellent performances of the PGMs on high efficiency, wideband, tunable beam steering. PMID- 26832469 TI - Simultaneous detection of atmospheric CH(4) and CO using a single tunable multi mode diode laser at 2.33 MUm. AB - We report on the first application (to our knowledge) of an extended-wavelength (2.33 MUm) multi-mode diode laser for simultaneous measurement of the concentrations of CH(4) and CO in the ambient air. The signals identification and quantitative analysis are performed using correlation spectroscopy. A Herriott cell and the wavelength modulation spectroscopy technique with second harmonic detection are also utilized to improve the detection sensitivity of the system. The detection limits of the system are estimated to be about 81 ppbv and 31 ppbv for CH(4) and CO, respectively. The accuracy, sensitivity, precision, and stability are also analyzed to confirm the potential of the system. PMID- 26832468 TI - Coherent Phi-OTDR based on I/Q demodulation and homodyne detection. AB - We demonstrate a novel distributed acoustic sensing (DAS) system based on phase sensitive optical time-domain reflectometry (Phi-OTDR). Both the phase and the amplitude of the Rayleigh scattering (RS) light can be demodulated in real-time. The technique is based on I/Q demodulation and homodyne detection using a 90 degrees optical hybrid. The theoretical analysis is given, and as a proof of the concept, the dynamic strain sensing is experimentally demonstrated, with a sensing range of 12.566 km and a spatial resolution of 10 m. PMID- 26832470 TI - Sub-wavelength sized transversely polarized optical needle with exceptionally suppressed side-lobes. AB - It is well known that radially polarized beam could produce an ultra-long longitudinally polarized focus, referred to as "optical needle". In this work, we reveal that the counterpart transversely polarized optical needle (~5.83lambda) with exceptionally suppressed sidelobes (9.9% of the maximum of the principal lobe) can be generated by tightly focusing a hybridly polarized beam through a multibelt binary phase filter. A universal analytical model is built up for investigating the depth, uniformity and polarization properties of the needle. We find that there is a trade-off between needle length and intensity uniformity, and the main lobe keeps almost transverse polarization at each observation plane. Such a nondiffraction transversely polarized optical needle has potential applications in ultrahigh density magnetic storage as well as atomic trap and switches. PMID- 26832471 TI - Regenerative thin-disk amplifier for 300 mJ pulse energy. AB - A regenerative amplifier based on thin-disk technology has been upgraded and optimized. Within a CPA laser system chirped 1 ns pulses are amplified to more than 300 mJ pulse energy. In addition to the high pulse energy the amplifier shows a very good energy stability with 0.25% (rms) fluctuation as well as an excellent beam quality of M(2) = 1.04. The regenerative amplifier is equipped with an Yb:YAG thin-disk of 17 mm in diameter pumped with 1.75 kW peak power. It is operated at a repetition rate of 100 Hz. The optical-to-optical efficiency is better than 18%. The laser pulses are compressed to 1.8 ps pulse duration. PMID- 26832472 TI - Mitigation of nonlinear distortion in hybrid Raman/phase-sensitive amplifier links. AB - Hybrid systems combining distributed Raman amplification and phase-sensitive amplifiers (PSAs) are investigated in numerical simulations. We focus on the mitigation of fiber nonlinearities and the impact of the span power map which is also important in systems employing optical phase conjugation or phase-conjugated twin waves. We simulate multi-span PSA links with and without distributed Raman amplification and show that by including distributed Raman amplification, the transmission distance increases more at optimum launch power than in the linear regime. For a 5-channel WDM QPSK PSA-amplified system, we observe a transmission reach increase by a factor of 8.1 by including ideal distributed Raman amplification. PMID- 26832473 TI - Efficient phase-matching for difference frequency generation with pump of Bessel laser beams. AB - A type of phase matching for difference frequency generation with Bessel-type pump beams is proposed. In this geometry, the phase matching is achieved in a cone around the laser path by properly controlling the beam profile. An experimental case that 1.5THz generation with ~2MUm lasers pumped bulk GaAs crystal is considered. Calculations of the energy conversion characteristics are performed based on a semi-analytical model. The results indicate that this configuration could relax the phase matching condition in a wide range of nonlinear crystals and pump wavelengths. PMID- 26832474 TI - Diffraction gratings generating orders with selective states of polarization. AB - We propose specially designed double anisotropic polarization diffraction gratings capable of producing a selective number of diffraction orders and with selective different states of polarization. Different polarization diffraction gratings are demonstrated, including linear polarization with horizontal, vertical and +/- 45 degrees orientations, and circular R and L polarization outputs. When illuminated with an arbitrary state of polarization, the system acts as a complete polarimeter where the intensities of the diffraction orders allow measurement of the Stokes parameters with a single shot. Experimental proof of-concept is presented using a parallel-aligned liquid crystal display operating in a double pass architecture. PMID- 26832475 TI - OWC using a monolithically integrated 200 um APD OEIC in 0.35 um BiCMOS technology. AB - A lens-less receiver with a monolithically integrated avalanche photodiode (APD) in 0.35 um BiCMOS technology has been developed for establishing an indoor 2 Gb/s optical wireless communication (OWC) over a distance of 6.5 m with a receiving angle of 22 degrees . Immunity toward background light was demonstrated up to 6000 lux. Four additional PIN photodiodes with highly sensitive differential nonlinear transimpedance amplifiers (TIA) were implemented on the receiver chip for centering the highly collimated transmitter beam position. PMID- 26832476 TI - Effects of the photonic sampling pulse width and the photodetection bandwidth on the channel response of photonic ADCs. AB - We investigate the effects of the photonic sampling pulse's temporal width and the photodetection bandwidth on the channel response of time-interleaved photonic analog-to-digital converters (TIPADCs). Each sampling channel is modeled as a linear analog channel with a sampler, where the channel response is derived and analyzed theoretically. The results show that the finite temporal width of photonic sampling pulse will limit the channel analog bandwidth and the minimum feasible bandwidth of photodetection is the half of single channel sampling rate. The inter-symbol interference (ISI) induced by the finite bandwidth of photodetection will cause periodic ripples on the channel frequency response. Neither the photonic sampling with finite temporal width nor the ISI induced by the finite bandwidth of photodetection will result in excess noise. Experimental measurements on the channel responses of a TIPADC under different temporal widths and photodetection bandwidths verify the theoretical results. PMID- 26832477 TI - Temporal response of laser power standards with natural convective cooling. AB - Laser power detectors with natural convective cooling are convenient to use and hence widely applicable in a power range below 150 W. However, the temporal response characteristics of the laser power detectors need to be studied in detail for accurate measurement. The temporal response based on the absolute laser power standards with natural convective cooling is studied through theoretical analysis, numerical simulations, and experimental verifications. Our results show that the response deviates from a single exponential function and that an ultimate response balance is difficult to achieve because the temperature rise of the heat sink leads to continuous increase of the response. To determine the measurement values, an equal time reading method is proposed and validated by the laser power calibrations. PMID- 26832478 TI - Calculations of band diagrams and low frequency dispersion relations of 2D periodic dielectric scatterers using broadband Green's function with low wavenumber extraction (BBGFL). AB - The broadband Green's function with low wavenumber extraction (BBGFL) is applied to the calculations of band diagrams of two-dimensional (2D) periodic structures with dielectric scatterers. Periodic Green's functions of both the background and the scatterers are used to formulate the dual surface integral equations by approaching the surface of the scatterer from outside and inside the scatterer. The BBGFL are applied to both periodic Green's functions. By subtracting a low wavenumber component of the periodic Green's functions, the broadband part of the Green's functions converge with a small number of Bloch waves. The method of Moment (MoM) is applied to convert the surface integral equations to a matrix eigenvalue problem. Using the BBGFL, a linear eigenvalue problem is obtained with all the eigenmodes computed simultaneously giving the multiband results at a point in the Brillouin zone Numerical results are illustrated for the honeycomb structure. The results of the band diagrams are in good agreement with the planewave method and the Korringa Kohn Rostoker (KKR) method. By using the lowest band around the Gamma point, the low frequency dispersion relations are calculated which also give the effective propagation constants and the effective permittivity in the low frequency limit. PMID- 26832479 TI - Directional couplers with integrated carbon nanotube incandescent light emitters. AB - We combine on-chip single-walled carbon nanotubes (SWNTs) emitters with directional coupling devices as fundamental building blocks for carbon photonic systems. These devices are essential for studying the emission properties of SWNTs in the few photon regime for future applications in on-chip quantum photonics. The combination of SWNTs with on-chip beam splitters herein provides the basis for correlation measurements as necessary for nanoscale source characterization. The employed fabrication methods are fully scalable and thus allow for implementing a multitude of functional and active circuits in a single fabrication run. Our metallic SWNT emitters are broadband and cover both visible and near-infrared wavelengths, thus holding promise for emerging hybrid optoelectronic devices with fast reconfiguration times. PMID- 26832480 TI - Mode instability thresholds for Tm-doped fiber amplifiers pumped at 790 nm. AB - We use a detailed numerical model of stimulated thermal Rayleigh scattering to compute mode instability thresholds in Tm(3+)-doped fiber amplifiers. The fiber amplifies 2040 nm light using a 790 nm pump. The cross-relaxation process is strong, permitting power efficiencies of 60%. The predicted instability thresholds are compared with those in similar Yb(3+)-doped fiber amplifiers with 976 nm pump and 1060 nm signal, and are found to be higher, even though the heat load is much higher in Tm-doped amplifiers. The higher threshold in the Tm-doped fiber is attributed to its longer signal wavelength, and to stronger gain saturation, due in part to cross-relaxation heating. PMID- 26832481 TI - Light propagation beyond the mean-field theory of standard optics. AB - With ready access to massive computer clusters we may now study light propagation in a dense cold atomic gas by means of basically exact numerical simulations. We report on a direct comparison between traditional optics, that is, electrodynamics of a polarizable medium, and numerical simulations in an elementary problem of light propagating through a slab of matter. The standard optics fails already at quite low atom densities, and the failure becomes dramatic when the average interatomic separation is reduced to around k(-1), where k is the wave number of resonant light. The difference between the two solutions originates from correlations between the atoms induced by light mediated dipole-dipole interactions. PMID- 26832482 TI - Highly sensitive optical temperature sensor based on a SiN micro-ring resonator with liquid crystal cladding. AB - This work develops a sensitivity-enhanced optical temperature sensor that is based on a silicon nitride (SiN) micro-ring resonator that incorporates nematic liquid crystal (NLC) cladding. As the ambient temperature changes, the refractive index of the NLCs, which have a large thermal-optical coefficient, dramatically varies. The change in the refractive index of the NLC cladding that is caused by the temperature shift can alter the effective refractive index of the micro-ring resonator and make the resonance wavelength very sensitive to the ambient temperature. The temperature-sensitivity of the device with 5CB cladding for TM polarized light was measured to be as high as 1nm/ degrees C between 25 and 33 degrees C and over 2nm/ degrees C at temperatures close to clearing temperature of the 5CB cladding. The temperature-sensitivity of the proposed device is at least 55 times that of the micro-ring resonator with air cladding, whose temperature-dependent wavelength shift for TM-polarized light is 18pm/ degrees C. PMID- 26832483 TI - High conversion efficiency in resonant four-wave mixing processes. AB - We propose a new scheme of the resonant four-wave mixing (FWM) for the frequency up or down conversion, which is more efficient than the commonly-used scheme of the non-resonant FWM. In this new scheme, two control fields are spatially varied such that a probe field at the input can be converted to a signal field at the output. The efficiency of probe-to-signal energy conversion can be 90% at medium's optical depth of about 100. Our proposed scheme works for both the continuous-wave and pulse cases, and is flexible in choosing the control field intensity. This work provides a very useful tool in the nonlinear frequency conversion. PMID- 26832484 TI - Direct design of aspherical lenses for extended non-Lambertian sources in three dimensional rotational geometry. AB - Illumination design used to redistribute the spatial energy distribution of light source is a key technique in lighting applications. However, there is still no effective illumination design method for extended sources, especially for extended non-Lambertian sources. What we present here is to our knowledge the first direct method for extended non-Lambertian sources in three-dimensional (3D) rotational geometry. In this method, both meridional rays and skew rays of the extended source are taken into account to tailor the lens profile in the meridional plane. A set of edge rays and interior rays emitted from the extended source which will take a given direction after the refraction of the aspherical lens are found by the Snell's law, and the output intensity at this direction is then calculated to be the integral of the luminance function of the outgoing rays at this direction. This direct method is effective for both extended non Lambertian sources and extended Lambertian sources in 3D rotational symmetry, and can directly find a solution to the prescribed design problem without cumbersome iterative illuminance compensation. Two examples are presented to demonstrate the effectiveness of the proposed method in terms of performance and capacity for tackling complex designs. PMID- 26832485 TI - Optical measurement of focal offset in tunable lenses. AB - Electrically tunable lenses are becoming a widely used optical tool, and have brought significant innovation to microscopy methods. One current limitation of such systems is the difficulty of directly monitor the focal change in real time. Affordable and reliable feedback for such lenses, compatible with any microscopy setup, represents a much-needed improvement that is still not widely available. We discuss here the implementation and technical performance of an optical device to measure with a high frequency response the displacement of the focal offset of a commercial tunable lens with a precision in the range of the axial Point Spread Function (PSF) of the microscope. The technology presented is cost effective and can be employed on any microscopy setup. PMID- 26832486 TI - Design and fabrication of an optical probe with a phase filter for extended depth of focus. AB - The trade-off between spot size and depth of focus (DOF) often limits the performance of optical systems, such as optical coherence tomography and optical tweezers. Although researchers have proposed various methods to extend the DOF in free-space optics, many are difficult to implement in miniaturized optical probes due to space limitations. In this study, we present an optical probe with an extended DOF using a binary phase spatial filter (BPSF). The BPSF pattern was fabricated on the distal tip of an optical probe with a diameter of 1 mm by replica molding soft lithography, which can be easily implemented in a miniaturized optical probe due to its simple configuration. We optimized the BPSF pattern to enhance DOF, spot diameter, and light efficiency. To evaluate the fabricated endoscopic optical probe, we measured the three-dimensional point spread function of the BPSF probe and compared it with a probe without BPSF. The BPSF probe has a spot diameter of 3.56 MUm and a DOF of 199.7 MUm, while the probe without BPSF has a spot diameter of 3.69 MUm and a DOF of 73.9 MUm, representing a DOF gain of 2.7. We anticipate that this optical probe can be used in biomedical applications, including optical imaging and optical trapping techniques. PMID- 26832487 TI - Timing jitter in synchronized time-lens source for coherent Raman scattering imaging: publisher's note. AB - This publisher's note amends the Acknowledgments of a recent publication [Opt. Express23,18786-18791 (2015)10.1364/OE.23.018786]. PMID- 26832488 TI - High-gain mid-infrared optical-parametric generation pumped by microchip laser. AB - High-gain mid-infrared optical-parametric generation was demonstrated by simple single-pass configuration using PPMgLN devices pumped by giant-pulse microchip laser. Effective mid-infrared wavelength conversion with 1 mJ output energy from 2.4 mJ pumping using conventional PPMgLN could be realized. Broadband optical parametric generation from 1.7 to 2.6 um could be also measured using chirped PPMgLN. PMID- 26832489 TI - High-speed frequency-domain terahertz coherence tomography. AB - High-speed frequency-domain terahertz (THz) coherence tomography is demonstrated using frequency sweeping of continuous-wave THz radiation and beam steering. For axial scanning, THz frequency sweeping with a kHz sweep rate and a THz sweep range is executed using THz photomixing with an optical beat source consisting of a wavelength-swept laser and a distributed feedback laser diode. During the frequency sweep, frequency-domain THz interferograms are measured using coherent homodyne detection employing signal averaging for noise reduction and used as axial-scan data via fast Fourier transform. Axial-scan data are acquired while scanning a transverse range of 100 * 100 mm(2) by use of a THz beam scanner with moving neither sample nor THz transmitter/receiver unit. It takes 100 s to acquire axial-scan data for 100 * 100 points with 5 averaged traces at a sweep rate of 1 kHz. THz tomographic images of a glass fiber reinforced polymer sample with artificial internal defects are presented, acquired using the tomography system. PMID- 26832490 TI - Stress-induced birefringence and fabrication of in-fiber polarization devices by controlled femtosecond laser irradiations. AB - Optical birefringence was created in a single-mode fiber by introducing a series of symmetric cuboid stress rods on both sides of the fiber core along the fiber axis using a femtosecond laser. The stress-induced birefringence was estimated to be 2.4 * 10(-4) at the wavelength of 1550 nm. By adding the desired numbers of stressed rods, an in-fiber quarter waveplate was fabricated with a insertion loss of 0.19 dB. The stress-induced birefringence was further explored to fabricate in fiber polarizers based on the polarization-dependent long-period fiber grating (LPFG) structure. A polarization extinction ratio of more than 20 dB was observed at the resonant wavelength of 1523.9 nm. The in-fiber polarization devices may be useful in optical communications and fiber optic sensing applications. PMID- 26832491 TI - Enhanced electron-hole droplet emission from surface-oxidized silicon photonic crystal nanocavities. AB - We have observed electron-hole droplet (EHD) emission enhanced by silicon photonic crystal (Si PhC) nanocavities with a surface oxide. The EHD is employed as a massive emitter that remains inside the nanocavity to achieve efficient cavity-emitter coupling. Time-resolved emission measurements demonstrate that the surface oxide greatly reduces the nonradiative annihilation of the EHDs and maintains them in the PhC nanocavities. It is found that the surface-oxidized Si PhC nanocavity enhances EHD emission in addition to the Purcell enhancement of the resonant cavity, which will contribute to works on Si light emission and the cavity quantum electrodynamics of electron-hole condensates. PMID- 26832492 TI - High power broadband all fiber super-fluorescent source with linear polarization and near diffraction-limited beam quality. AB - In this manuscript, a high power broadband superfluorescent source (SFS) with linear polarization and near-diffraction-limited beam quality is achieved based on an ytterbium-doped (Yb-doped), all fiberized and polarization-maintained master oscillator power amplifier (MOPA) configuration. The MOPA structure generates a linearly polarized output power of 1427 W with a slope efficiency of 80% and a full width at half maximum (FWHM) of 11 nm, which is power scaled by an order of magnitude compared with the previously reported SFSs with linear polarization. In the experiment, both the polarization extinction ratio (PER) and beam quality (M(2) factor) are degraded little during the power scaling process. At maximal output power, the PER and M(2) factor are measured to be 19.1dB and 1.14, respectively. The root-mean-square (RMS) and peak-vale (PV) values of the power fluctuation at maximal output power are just 0.48% and within 3%, respectively. Further power scaling of the whole system is limited by the available pump sources. To the best of our knowledge, this is the first demonstration of kilowatt level broadband SFS with linear polarization and near diffraction-limited beam quality. PMID- 26832493 TI - Gain guided and index alternate-guided fibers designed for large-mode-area and single-mode laser with higher output power and slope efficiency. AB - A gain guided and index alternate-guided fiber (GGIA-GF) is proposed and numerically demonstrated. The conditions of single mode oscillation are analyzed based on the fiber laser parameters. The output laser power and slope efficiency of the GGIA-GF laser are derived from the improved rate equations. The results show that the output characteristics of the laser based on GGIA-GF can be greatly improved than that of the gain guided and index anti-guided fiber laser through the optimal design of the fiber laser parameters. GGIA-GF would be better applied in the field of large mode area and single mode fiber lasers. PMID- 26832494 TI - Approaching single temporal mode operation in twin beams generated by pulse pumped high gain spontaneous four wave mixing. AB - By investigating the intensity correlation function, we study the spectral/temporal mode properties of twin beams generated by the pulse-pumped high gain spontaneous four wave mixing (SFWM) in optical fiber from both the theoretical and experimental aspects. The results show that the temporal property depends not only on the phase matching condition and the filters applied in the signal and idler fields, but also on the gain of SFWM. When the gain of SFWM is low, the spectral/temporal mode properties of the twin beams are determined by the phase matching condition and optical filtering and are usually of multi-mode nature, which leads to a value larger than 1 but distinctly smaller than 2 for the normalized intensity correlation function of individual signal/idler beam. However, when the gain of SFWM is very high, we demonstrate the normalized intensity correlation function of individual signal/idler beam approaches to 2, which is a signature of single temporal mode. This is so even if the frequencies of signal and idler fields are highly correlated so that the twin beams have multiple modes in low gain regime. We find that the reason for this behavior is the dominance of the fundamental mode over other higher order modes at high gain. Our investigation is useful for constructing high quality multi-mode squeezed and entangled states by using pulse-pumped spontaneous parametric down-conversion and SFWM. PMID- 26832495 TI - Imaging scatterometry for flexible measurements of patterned areas. AB - Characterization of micro/nano-textured surfaces is time consuming using scanning probe and electron microscopy techniques. Scatterometry, where the intensity of scattered light is used as a 'fingerprint' to reconstruct a surface, is a fast and robust method for characterization of gratings. However, most scatterometry techniques are measuring the averaged signal over an area equal to the spot size of the light source. In this paper we present the imaging scatterometry technique, which is capable of locally measuring topographic parameters of gratings spanning an area down to a few um(2) with nm accuracy. The imaging scatterometer can easily find areas of interest on the cm scale and measure multiple segments simultaneously. We demonstrate two imaging scatterometers, one built into an optical microscope and one in a split configuration. The two scatterometers are targeted characterization of mm(2) and cm(2) areas, respectively, and both setups are validated using nano-textured samples. PMID- 26832496 TI - Three-dimensional temperature field measurement of flame using a single light field camera. AB - Compared with conventional camera, the light field camera takes the advantage of being capable of recording the direction and intensity information of each ray projected onto the CCD (charge couple device) sensor simultaneously. In this paper, a novel method is proposed for reconstructing three-dimensional (3-D) temperature field of a flame based on a single light field camera. A radiative imaging of a single light field camera is also modeled for the flame. In this model, the principal ray represents the beam projected onto the pixel of the CCD sensor. The radiation direction of the ray from the flame outside the camera is obtained according to thin lens equation based on geometrical optics. The intensities of the principal rays recorded by the pixels on the CCD sensor are mathematically modeled based on radiative transfer equation. The temperature distribution of the flame is then reconstructed by solving the mathematical model through the use of least square QR-factorization algorithm (LSQR). The numerical simulations and experiments are carried out to investigate the validity of the proposed method. The results presented in this study show that the proposed method is capable of reconstructing the 3-D temperature field of a flame. PMID- 26832497 TI - Binary coded patterns for photon control using necklace problem concept. AB - Pseudo-disordered structures enable additional design freedom for photon management. However, the optimization and interpretation is challenging when the large number of degrees of freedom encounters computationally intensive electromagnetic simulation method. Here we propose a novel one-dimensional multi periodic pattern generation method to help us squeeze the disorder design space before performing rigorous calculation, by making use of the periodic attribute of the pattern. Consequently, thanks to the pre-filtered design space, it typically relieves us from computational burden and enables us to 'globally' optimize and study pseudo-disordered patterns. As an example, we show how this approach can be used to comprehensively optimize and systematically analyze generated disorder for broadband light trapping in thin film. PMID- 26832498 TI - Plasmonic arrays of titanium nitride nanoparticles fabricated from epitaxial thin films. AB - We have fabricated two-dimensional periodic arrays of titanium nitride (TiN) nanoparticles from epitaxial thin films. The thin films of TiN, deposited on sapphire and single crystalline magnesium oxide substrates by a pulsed laser deposition, are metallic and show reasonably small optical loss in the visible and near infrared regions. The thin films prepared were structured to the arrays of nanoparticles with the pitch of 400 nm by the combination of nanoimprint lithography and reactive ion etching. Optical transmission indicates that the arrays support the collective plasmonic modes, where the localized surface plasmon polaritons in TiN nanoparticles are radiatively coupled through diffraction. Numerical simulation visualizes the intense fields accumulated both in the nanoparticles and in between the particles, confirming that the collective mode originates from the simultaneous excitation of localized surface plasmon polaritons and diffraction. This study experimentally verified that the processing of TiN thin films with the nanoimprint lithography and reactive ion etching is a powerful and versatile way of preparing plasmonic nanostructures. PMID- 26832499 TI - Nanoscale plasmonic phenomena in CVD-grown MoS(2) monolayer revealed by ultra broadband synchrotron radiation based nano-FTIR spectroscopy and near-field microscopy. AB - Nanoscale plasmonic phenomena observed in single and bi-layers of molybdenum disulfide (MoS(2)) on silicon dioxide (SiO(2)) are reported. A scattering type scanning near-field optical microscope (s-SNOM) with a broadband synchrotron radiation (SR) infrared source was used. We also present complementary optical mapping using tunable CO(2)-laser radiation. Specifically, there is a correlation of the topography of well-defined MoS(2) islands grown by chemical vapor deposition, as determined by atomic force microscopy, with the infrared (IR) signature of MoS(2). The influence of MoS(2) islands on the SiO(2) phonon resonance is discussed. The results reveal the plasmonic character of the MoS(2) structures and their interaction with the SiO(2) phonons leading to an enhancement of the hybridized surface plasmon-phonon mode. A theoretical analysis shows that, in the case of monolayer islands, the coupling of the MoS(2) optical plasmon mode to the SiO(2) surface phonons does not affect the infrared spectrum significantly. For two-layer MoS(2), the coupling of the extra inter-plane acoustic plasmon mode with the SiO(2) surface transverse phonon leads to a remarkable increase of the surface phonon peak at 794 cm(-1). This is in agreement with the experimental data. These results show the capability of the s SNOM technique to study local multiple excitations in complex non-homogeneous structures. PMID- 26832500 TI - Bright source of polarization-entangled photons using a PPKTP pumped by a broadband multi-mode diode laser. AB - We report a bright source of polarization-entangled photon pairs using spontaneous parametric down-conversion (SPDC) in a 10 mm long type-II PPKTP crystal pumped by a broadband multi-mode diode laser with the coherence length of 330 MUm. Ordinarily, the huge mismatch between the pump coherence length and the PPKTP length would degrade the polarization entanglement completely. By employing the universal Bell-state synthesizer scheme, we remove the spectral/temporal distinguishability of the biphoton amplitudes entirely to recover high-visibility and high-fidelity two-photon polarization entanglement. The pair detection rates are 7,000 pairs/mW via single-mode fibers (with 99.2% fidelity) and 90,900 pairs/mW via multi-mode fibers (with 96.8% fidelity). We also analyze the scheme theoretically to show the effect of broadband multi-mode pumping on the phase matching condition of the type-II PPKTP. PMID- 26832501 TI - Noise-induced bias for convolution-based interpolation in digital image correlation. AB - In digital image correlation (DIC), the noise-induced bias is significant if the noise level is high or the contrast of the image is low. However, existing methods for the estimation of the noise-induced bias are merely applicable to traditional interpolation methods such as linear and cubic interpolation, but are not applicable to generalized interpolation methods such as BSpline and OMOMS. Both traditional interpolation and generalized interpolation belong to convolution-based interpolation. Considering the widely use of generalized interpolation, this paper presents a theoretical analysis of noise-induced bias for convolution-based interpolation. A sinusoidal approximate formula for noise induced bias is derived; this formula motivates an estimating strategy which is with speed, ease, and accuracy; furthermore, based on this formula, the mechanism of sophisticated interpolation methods generally reducing noise-induced bias is revealed. The validity of the theoretical analysis is established by both numerical simulations and actual subpixel translation experiment. Compared to existing methods, formulae provided by this paper are simpler, briefer, and more general. In addition, a more intuitionistic explanation of the cause of noise induced bias is provided by quantitatively characterized the position-dependence of noise variability in the spatial domain. PMID- 26832502 TI - Three-dimensional IR imaging with uncooled GaN photodiodes using nondegenerate two-photon absorption. AB - We utilize the recently demonstrated orders of magnitude enhancement of extremely nondegenerate two-photon absorption in direct-gap semiconductor photodiodes to perform scanned imaging of three-dimensional (3D) structures using IR femtosecond illumination pulses (1.6 um and 4.93 um) gated on the GaN detector by sub-gap, femtosecond pulses. While transverse resolution is limited by the usual imaging criteria, the longitudinal or depth resolution can be less than a wavelength, dependent on the pulsewidths in this nonlinear interaction within the detector element. The imaging system can accommodate a wide range of wavelengths in the mid-IR and near-IR without the need to modify the detection and imaging systems. PMID- 26832503 TI - Temperature insensitive hysteresis free highly sensitive polymer optical fiber Bragg grating humidity sensor. AB - The effect of humidity on annealing of poly (methyl methacrylate) (PMMA) based microstructured polymer optical fiber Bragg gratings (mPOFBGs) and the resulting humidity responsivity are investigated. Typically annealing of PMMA POFs is done in an oven without humidity control around 80 degrees C and therefore at low humidity. We demonstrate that annealing at high humidity and high temperature improves the performances of mPOFBGs in terms of stability and sensitivity to humidity. PMMA POFBGs that are not annealed or annealed at low humidity level will have a low and highly temperature dependent sensitivity and a high hysteresis in the humidity response, in particular when operated at high temperature. PMMA mPOFBGs annealed at high humidity show higher and more linear humidity sensitivity with negligible hysteresis. We also report how annealing at high humidity can blue-shift the FBG wavelength more than 230 nm without loss in the grating strength. PMID- 26832505 TI - Flexible calibration method for telecentric fringe projection profilometry systems. AB - A newly developed flexible calibration algorithm for telecentric 3D measurement systems is presented in this paper. We theoretically analyzed the similarities and differences between the telecentric and entocentric system. The telecentric system can be calibrated with the aid of the traditional 2D planar calibration method. An additional two-step refining process is proposed to improve the calibration accuracy effectively. With the calibration and refining algorithm, an affine camera can be calibrated with a reprojection error of 0.07 pixel. A projector with small field of view (FOV) is applied to achieve a full 3D reconstruction in our profilometry system. Experiments with a prototype demonstrate the validation and accuracy of the proposed calibration algorithm and system configuration. The reconstruction accuracy can achieve 5 um with a measurement FOV of 28.43 mm*21.33 mm and a working distance of 110 mm. PMID- 26832504 TI - In vivo volumetric imaging of biological dynamics in deep tissue via wavefront engineering. AB - Biological systems undergo dynamical changes continuously which span multiple spatial and temporal scales. To study these complex biological dynamics in vivo, high-speed volumetric imaging that can work at large imaging depth is highly desired. However, deep tissue imaging suffers from wavefront distortion, resulting in reduced Strehl ratio and image quality. Here we combine the two wavefront engineering methods developed in our lab, namely the optical phase locked ultrasound lens based volumetric imaging and the iterative multiphoton adaptive compensation technique, and demonstrate in vivo volumetric imaging of microglial and mitochondrial dynamics at large depth in mouse brain cortex and lymph node, respectively. PMID- 26832506 TI - Reducing the phase sensitivity of laser-based optical reservoir computing systems. AB - Optical implementations of reservoir computing systems are very promising because of their high processing speeds and the possibility to process several tasks in parallel. These systems can be implemented using semiconductor lasers subject to optical delayed feedback and optical injection. While the amount of the feedback/injection can be easily controlled, it is much more difficult to control the optical feedback/injection phase. We present extensive numerical investigations of the influence of the feedback/injection phases on laser-based reservoir computing systems with feedback. We show that a change in the phase can lead to a strong reduction in the reservoir computing system performance. We introduce a new readout layer design that -at least for some tasks- reduces this sensitivity to changes in the phase. It consists in optimizing the readout weights from a coherent combination of the reservoir's readout signal and its delayed version rather than only from the reservoir's readout signal as is usually done. PMID- 26832507 TI - Single mode step-index polymer optical fiber for humidity insensitive high temperature fiber Bragg grating sensors. AB - We have fabricated the first single-mode step-index and humidity insensitive polymer optical fiber operating in the 850 nm wavelength ranges. The step-index preform is fabricated using injection molding, which is an efficient method for cost effective, flexible and fast preparation of the fiber preform. The fabricated single-mode step-index (SI) polymer optical fiber (POF) has a 4.8um core made from TOPAS grade 5013S-04 with a glass transition temperature of 134 degrees C and a 150 um cladding made from ZEONEX grade 480R with a glass transition temperature of 138 degrees C. The key advantages of the proposed SIPOF are low water absorption, high operating temperature and chemical inertness to acids and bases and many polar solvents as compared to the conventional poly methyl-methacrylate (PMMA) and polystyrene based POFs. In addition, the fiber Bragg grating writing time is short compared to microstructured POFs. PMID- 26832508 TI - Analysis of mobile fronthaul bandwidth and wireless transmission performance in split-PHY processing architecture. AB - We analyze the mobile fronthaul (MFH) bandwidth and the wireless transmission performance in the split-PHY processing (SPP) architecture, which redefines the functional split of centralized/cloud RAN (C-RAN) while preserving high wireless coordinated multi-point (CoMP) transmission/reception performance. The SPP architecture splits the base stations (BS) functions between wireless channel coding/decoding and wireless modulation/demodulation, and employs its own CoMP joint transmission and reception schemes. Simulation results show that the SPP architecture reduces the MFH bandwidth by up to 97% from conventional C-RAN while matching the wireless bit error rate (BER) performance of conventional C-RAN in uplink joint reception with only 2-dB signal to noise ratio (SNR) penalty. PMID- 26832509 TI - Compressed imaging by sparse random convolution. AB - The theory of compressed sensing (CS) shows that signals can be acquired at sub Nyquist rates if they are sufficiently sparse or compressible. Since many images bear this property, several acquisition models have been proposed for optical CS. An interesting approach is random convolution (RC). In contrast with single-pixel CS approaches, RC allows for the parallel capture of visual information on a sensor array as in conventional imaging approaches. Unfortunately, the RC strategy is difficult to implement as is in practical settings due to important contrast-to-noise-ratio (CNR) limitations. In this paper, we introduce a modified RC model circumventing such difficulties by considering measurement matrices involving sparse non-negative entries. We then implement this model based on a slightly modified microscopy setup using incoherent light. Our experiments demonstrate the suitability of this approach for dealing with distinct CS scenarii, including 1-bit CS. PMID- 26832510 TI - Loss-induced super scattering and gain-induced absorption. AB - Giant transmission and reflection of a finite bandwidth are demonstrated at the same wavelength when the electromagnetic wave is incident on a subwavelength array of parity-time (PT) symmetric dimers embedded in a metallic film. Remarkably, this phenomenon vanishes if the metallic substrate is lossless while keeping other parameters unchanged. Moreover super scattering can also occur when increasing the loss of the dimers while keeping the gain unchanged. When the metafilm is adjusted to the vicinity of an exceptional point, tuning either the substrate dissipation or the loss of the dimers can lead to supper scattering in stark contrast to what would be expected in conventional systems. In addition, increasing the gain of the dimers can increase the absorption near the exceptional point. These phenomena indicate that the PT-synthetic plasmonic metafilm can function as a thinfilm PT-plasmonic laser or absorber depending on the tuning parameter. One implication is that super radiation is possible from a cavity by tuning cavity dissipation or lossy element inside the cavity. PMID- 26832511 TI - Novel ultra-thin near-eye augmented-view device (UNAD). AB - The current augmented-view device for glaucoma patients are limited by the low angle minification (less than 3X), image overlapping and pupil mismatching. We present a novel ultra-thin near-eye augmented-view device (UNAD) with a proper minification angle of 4X to avoid scanning eye movements. The device is realized by one symmetrical ultra-thin off-axis eight-mirror reversed telescopic optical system (field-of-view (FOV): x:-34 degrees ~3 degrees ; y: -5 degrees ~-20 degrees , 5 degrees ~20 degrees ) and one central un-minified optical system (FOV: -5 degrees ~5 degrees ), and hence, the system can achieve a FOV (x:-34 degrees ~3 degrees ; y: -20 degrees ~20 degrees ) without overlapping images. Furthermore, the device fully accounts for pupil matching with the entrance pupil of the human eye. Finally, the simulation results in CODE V and LightTools verify that our proposed system is feasible and has potential practical value for glaucoma patients. PMID- 26832512 TI - Analysis of single mass-regulated particles in precisely controlled trap using laser-induced breakdown spectroscopy. AB - We report the influence of water content, droplet displacement and laser fluence on the laser-induced breakdown spectroscopy (LIBS) signal of precisely controlled single droplets. For the first time in single particle LIBS scheme, the degree of evaporation of an additive-free droplet was followed and the position of the residual particle was adjusted at micrometer resolution using electrodynamic trapping. The results show signal intensification throughout the 6 s period of the complete evaporation of the droplet into a dry residual particle. The analyte line emission remained stable when the particle was moved within the focal spot area and almost tenfold compared with situation where the particle lies 15 MUm outside the laser beam path. Combination of low, about 6 mJ, excitation laser pulse energy and short, about 1 MUs detection delay time was found to be the optimal in the detection of most metals. The presented findings will pave the way for more sensitive and reproducible single particle elemental analysis exploited in the real-time monitoring of water, atmospheric aerosols or industrial emissions. PMID- 26832513 TI - Tunable dual-wavelength fiber laser with ultra-narrow linewidth based on Rayleigh backscattering. AB - Dual-wavelength fiber lasers with ultra-narrow linewidth find wide applications in high-speed optical communications, fiber optic sensors, high resolution measurements and medical instruments and microwave or terahertz generation systems. Based on the linewidth compression mechanism due to Rayleigh backscattering, this paper adopts a simple ring structure cooperated with two fiber Bragg gratings centered at 1550 nm and 1530 nm respectively, achieving a dual-wavelength fiber laser with ultra-narrow linewidth, with a 3dB linewidth of ~700 Hz for each wavelength, and the SNR of 60dB. Tuning the center wavelength of one of the two FBGs while the other one keeps unchanged, the fiber laser keeps stable dual-wavelength lasing and the linewidth is still ~700 Hz. It can be seen that the compression for the linewidth based on the Rayleigh backscattering can be used in multi-wavelength laser systems, and because of the characteristic of the Rayleigh backscattering, the method has great potential in the application of wide wavelength range linewidth compression from the ultraviolet to the far infrared. PMID- 26832514 TI - Efficient noiseless linear amplification for light fields with larger amplitudes. AB - We suggest and investigate a scheme for non-deterministic noiseless linear amplification of coherent states using successive photon addition, (a(?))(2), where a(?) is the photon creation operator. We compare it with a previous proposal using the photon addition-then-subtraction, aa(?), where a is the photon annihilation operator, that works as an appropriate amplifier only for weak light fields. We show that when the amplitude of a coherent state is |alpha| ? 0.91, the (a(?))(2) operation serves as a more efficient amplifier compared to the aa(?) operation in terms of equivalent input noise. Using aa(?) and (a(?))(2) as basic building blocks, we compare combinatorial amplifications of coherent states using (aa(?))(2), a(?4), aa(?)a(?2), and a(?2)aa(?), and show that (aa(?))(2), a(?2)aa(?), and a(?4) exhibit strongest noiseless properties for |alpha| ? 0.51, 0.51 ? |alpha| ? 1.05, and |alpha| ? 1.05, respectively. We further show that the (a(?))(2) operation can be useful for amplifying superpositions of the coherent states. In contrast to previous studies, our work provides efficient schemes to implement a noiseless amplifier for light fields with medium and large amplitudes. PMID- 26832515 TI - Few-femtosecond timing jitter from a picosecond all-polarization-maintaining Yb fiber laser. AB - We characterize the timing jitter of a picosecond all-polarization-maintaining (all-PM) Yb-fiber laser using the optical cross-correlation method. For the 10 MHz all-normal dispersion mode-locked laser with ~0.5 nm spectral bandwidth, the measured high-frequency jitter is as low as 5.9 fs (RMS) when integrated from 10 kHz to the Nyquist frequency of 5 MHz. A complete numerical model with ASE noise is built to simulate the timing jitter characteristics in consideration of intracavity pulse evolution. The mutual comparison among simulation result, analytical model and experiment data indicate that the few femtosecond timing jitter from the picosecond fiber laser is attributed to the complete elimination of Gordon-Haus jitter by narrow bandpass filtering by a fiber Bragg grating (FBG). The low level of timing jitter from this compact and maintenance-free PM picosecond fiber laser source at a low MHz repetition rate is promising to advance a number of femtosecond-precision timing and synchronization applications. PMID- 26832517 TI - Highly accurate fiber transfer delay measurement with large dynamic range. AB - A novel and efficient method for fiber transfer delay measurement is demonstrated. Fiber transfer delay measurement in time domain is converted into the frequency measurement of the modulation signal in frequency domain, accompany with a coarse and easy ambiguity resolving process. This method achieves a sub picosecond resolution, with an accuracy of 1 picosecond, and a large dynamic range up to 50 km as well as no measurement dead zone. PMID- 26832516 TI - Study of GeSn based heterostructures: towards optimized group IV MQW LEDs. AB - We present results on CVD growth and electro-optical characterization of Ge(0.92)Sn(0.08)/Ge p-i-n heterostructure diodes. The suitability of Ge as barriers for direct bandgap GeSn active layers in different LED geometries, such as double heterostructures and multi quantum wells is discussed based on electroluminescence data. Theoretical calculations by effective mass and 6 band k?p method reveal low barrier heights for this specific structure. Best configurations offer only a maximum barrier height for electrons of about 40 meV at the Gamma point at room temperature (e.g. 300 K), evidently insufficient for proper light emitting devices. An alternative solution using SiGeSn as barrier material is introduced, which provides appropriate band alignment for both electrons and holes resulting in efficient confinement in direct bandgap GeSn wells. Finally, epitaxial growth of such a complete SiGeSn/GeSn/SiGeSn double heterostructure including doping is shown. PMID- 26832518 TI - Adiabatically tapered microstructured mode converter for selective excitation of the fundamental mode in a few mode fiber. AB - We propose a new technique to selectively excite the fundamental mode in a few mode fiber (FMF). This method of excitation is made from a single mode fiber (SMF) which is inserted facing the FMF into an air-silica microstructured cane before the assembly is adiabatically tapered. We study theoretically and numerically this method by calculating the effective indices of the propagated modes, their amplitudes along the taper and the adiabaticity criteria, showing the ability to achieve an excellent selective excitation of the fundamental mode in the FMF with negligible loss. We experimentally demonstrate that the proposed solution provides a successful mode conversion and allows an almost excellent fundamental mode excitation in the FMF (representing 99.8% of the total power). PMID- 26832519 TI - Low loss ridge waveguides in lithium niobate thin films by optical grade diamond blade dicing. AB - We report on the fabrication and characterization of ridge waveguides in lithium niobate thin films by diamond blade dicing. The lithium niobate thin films with a thickness of 1 um were fabricated by bonding a He-implanted lithium niobate wafer to a SiO(2)-coated lithium niobate wafer and crystal ion slicing. Propagation losses of 1.2 dB/cm for TE and 2.8 dB/cm for TM polarization were measured at 1550 nm for a 9.28 mm long and 2.1 um wide waveguide using the Fabry-Perot method. PMID- 26832520 TI - Simultaneous cooling of coupled mechanical oscillators using whispering gallery mode resonances. AB - We demonstrate simultaneous center-of-mass cooling of two coupled oscillators, consisting of a microsphere-cantilever and a tapered optical fiber. Excitation of a whispering gallery mode (WGM) of the microsphere, via the evanescent field of the taper, provides a transduction signal that continuously monitors the relative motion between these two microgram objects with a sensitivity of 3 pm. The cavity enhanced optical dipole force is used to provide feedback damping on the motion of the micron-diameter taper, whereas a piezo stack is used to damp the motion of the much larger (up to 180 MUm in diameter), heavier (up to 1.5 * 10(-7) kg) and stiffer microsphere-cantilever. In each feedback scheme multiple mechanical modes of each oscillator can be cooled, and mode temperatures below 10 K are reached for the dominant mode, consistent with limits determined by the measurement noise of our system. This represents stabilization on the picometer level and is the first demonstration of using WGM resonances to cool the mechanical modes of both the WGM resonator and its coupling waveguide. PMID- 26832521 TI - Cryogenically-cooled Yb:YGAG ceramic mode-locked laser. AB - This work reports on a liquid-nitrogen-cooled, SESAM mode-locked Yb:YGAG (Yb:Y(3)Ga(2)Al(3)O(12)) ceramic laser. The Yb:YGAG has a similar structure to Yb:YAG, but its emission spectrum at low temperature remains much broader, which is suitable for ultrashort pulse generation and amplification. A stable pulse train with 119-MHz repetition rate was obtained at a wavelength of 1026 nm. The measured pulse duration is 2.4 ps, which is more than four times shorter than that achieved with a cryogenically-cooled Yb:YAG. Furthermore, laser performance of the Yb:YGAG ceramics in continuous-wave operation and wavelength tunability at 80 K was investigated. PMID- 26832522 TI - Design of asymmetric freeform lens for low glared LED street light with total internal reflection. AB - The study is focused on the asymmetric secondary freeform lens (ASFL) design for creating a low glared light-emitting diode (LED) street light. The lens is mounted on a chip on board (COB) LED as the new LED street light module to perform a non-axial symmetric light intensity distribution. The experimental results show that the street light can work without inclining lamps and reach Chinese National Standards (CNS) and Illuminating Engineering Society of North America (IESNA) standards at the same time. PMID- 26832523 TI - Design and performance estimate of a focal reducer for the 2.3 m Thai National Telescope. AB - We have designed a new kind of focal reducer for the 2.3 m Thai National Telescope (TNT) to image the TNT specified FOV Deltatheta = 14.6' with an angular resolution alpha ~1.2 arcsec. This, at a minimum cost by using common glasses, spherical surfaces and by requiring comfortable mechanical tolerance. This focal reducer comprises 1 lens placed at the level of the fork entrance and 1 lens placed in front of the detector. In this paper, we present the focal reducer paraxial model, we describe the optical design and we present the performance. PMID- 26832524 TI - Printing of metallic 3D micro-objects by laser induced forward transfer. AB - Digital printing of 3D metal micro-structures by laser induced forward transfer under ambient conditions is reviewed. Recent progress has allowed drop on demand transfer of molten, femto-liter, metal droplets with a high jetting directionality. Such small volume droplets solidify instantly, on a nanosecond time scale, as they touch the substrate. This fast solidification limits their lateral spreading and allows the fabrication of high aspect ratio and complex 3D metal structures. Several examples of micron-scale resolution metal objects printed using this method are presented and discussed. PMID- 26832525 TI - Direct CO(2) laser-based generation of holographic structures on the surface of glass. AB - A customized CO(2) laser micromachining system was used for the generation of phase holographic structures directly on the surface of fused silica (HPFS((r))7980 Corning) and Borofloat((r))33 (Schott AG) glass. This process used pulses of duration 10us and nominal wavelength 10.59um. The pulse energy delivered to the glass workpiece was controlled by an acousto-optic modulator. The laser-generated structures were optically smooth and crack free. We demonstrated their use as diffractive optical elements (DOEs), which could be exploited as anti-counterfeiting markings embedded into valuable glass-made components and products. PMID- 26832526 TI - Controlling liquid crystal pretilt angle with photocurable prepolymer and vertically aligned substrate. AB - We demonstrate a new approach to control the pretilt angle of liquid crystals (LCs) with photocurable prepolymer in a cell fabricated with vertically aligned substrates. During UV exposure, prepolymer approaches and is polymerized on the substrate surfaces because of the vertical phase separation induced by differences in the surface tensions of the employed materials. After polymerization, the polymer structure formed on the substrate alters its surface polarity and changes the pretilt angle of the LC cell. The LC pretilt angle can be controlled from 87.3 degrees to 2.5 degrees when the prepolymer concentration ranges from 0 wt% to 2.5 wt%. PMID- 26832527 TI - Detection of partial polarization of light beams with dipolar nanocubes. AB - We confirm experimentally that the degree and state of polarization of a random, partially polarized electromagnetic beam can be obtained by probing the field with a nanoscatterer. We use a gold nanocube on silicon substrate as a local scatterer and detect the polarization characteristics of the scattered far field, which enables us to deduce the state of partial polarization of the field at the nanoprobe site. In contrast to previous beam characterization methods where spatial resolution is limited by the pixel size of the detector, the accuracy of the current technique is specified by the particle size. Our work is the first step towards polarization-state detection of random optical near fields for which the use of nanoprobes is required. PMID- 26832528 TI - Band structure and dispersion engineering of strongly coupled plasmon-phonon polaritons in graphene-integrated structures. AB - We theoretically investigate the polaritonic band structure and dispersion properties of graphene using transfer matrix methods, with strongly coupled graphene plasmons (GPs) and molecular infrared vibrations as a representative example. Two common geometrical configurations are considered: graphene coupled subwavelength dielectric grating (GSWDG) and graphene nanoribbons (GNR). By exploiting the dispersion and the band structure, we show the possibility of tailoring desired polaritonic behavior in each of the two configurations. We compare the strength of coupling occurring in both structures and find that the interaction is stronger in GNR than that of GSWDG structure as a result of the stronger field confinement of the edge modes. The band structure and dispersion analysis not only sheds light on the physics of the hybridized polariton formation but also offers insight into tailoring the optical response of graphene light-matter interactions for numerous applications, such as biomolecular sensing and detection. PMID- 26832529 TI - Experimental study of the interaction between DC discharge microplasmas and CW lasers. AB - A high power (~ 1W) continuous wave (CW) laser was focused on argon microplasma generated in the microgap between two electrodes with submillimeter diameters. Dependence of breakdown (V(BD)) and quench (V(Q)) voltages of microplasma to the laser power, wavelength, and spot location were studied as the gap size and pressure varied. It was observed that the laser-plasma interaction can only occur thermally through the electrodes. Also, the thermal effect of the laser was noticeable at relatively higher pressures (> 10Torr), and in most cases led to a decrease in V(BD), proportional to the pressure. PMID- 26832530 TI - Quantitative detection of metallic traces in water-based liquids by microwave assisted laser-induced breakdown spectroscopy. AB - The enhancement of laser-induced breakdown spectroscopy (LIBS) assisted with microwave radiation is demonstrated for an aqueous solution of indium using the 451.13 nm emission line. Microwave power was delivered via a near-field applicator to the LIBS measurement volume where the indium aqueous solution was presented as a liquid jet. The microwave enhancement effect was observed to decrease with increasing laser pulse fluence at 532 nm resulting in a maximum emission intensity occurring at a laser pulse fluence of 85.2 J?cm(-2), independent of the microwave power used. The detection limits of indium in an aqueous solution were determined to be 10.8 +/- 0.7 and 124 +/- 5 ppm for the cases of microwave enhanced and standard LIBS, respectively. The 11.5-fold detection limit enhancement obtained in the liquid phase is of the same order of magnitude as that reported for other elements in solid samples, but lower than that obtained in solid phase utilizing a similar experimental setup. This establishes microwave enhancement as an effective technique for the detection of metals in aqueous solutions. In addition, the temporal evolution of plasma emission intensity was investigated and was found to be qualitatively similar to that of plasma produced from solid phase samples, which reveals the same coupling mechanism between laser generated plasma and microwave radiation. PMID- 26832531 TI - Dual-band tunable perfect metamaterial absorber in the THz range. AB - In this paper, a dual-band perfect absorber, composed of a periodically patterned elliptical nanodisk graphene structure and a metal ground plane spaced by a thin SiO(2) dielectric layer, is proposed and investigated. Numerical results reveal that the absorption spectrum of the graphene-based structure displays two perfect absorption peaks in the terahertz band, corresponding to the absorption value of 99% at 35MUm and 97%at 59MUm, respectively. And the resonance frequency of the absorber can be tunned by controlling the Fermi level of graphene layer. Further more, it is insensitive to the polarization and remains very high over a wide angular range of incidence around +/-60(0). Compared with the previous graphene dual-band perfect absorption, our absorber only has one shape which can greatly simplify the manufacturing process. PMID- 26832532 TI - Unimorph deformable mirror for space telescopes: environmental testing. AB - We have developed and manufactured a unimorph deformable mirror for space telescopes based on piezoelectric actuation. The mirror features 44 actuators, has an aperture of 50 mm, and is designed to reproduce low-order Zernike modes with a stroke of several tens of MUm. We assessed the space compliance by operating the mirror in thermal vacuum, and exposing it to random and sinusoidal vibrations, as well as to ionizing irradiation. Additionally, the operational life time and the laser power handling capability were tested. The mirror was successfully operated in thermal vacuum at 100 K. We report on the conducted tests and the methods used to evaluate the mirror's performance, and discuss the compliance with the demanded requirements. PMID- 26832533 TI - Evaluating and overcoming the impact of second echo in Brillouin echoes distributed sensing. AB - The detrimental impact of the second echo phenomenon that commonly exists in Brillouin echoes distributed sensing (BEDS) methods is thoroughly investigated by further developing the analytical model of the Brillouin gain on the probe wave. The presented analysis not only points out that the most severe impact imposed by the second echo occurs when the length of the heated/stressed fiber section is exactly equal to the spatial resolution, but also quantifies the systematic error on the estimated Brillouin frequency shift, the maximum of which could reach up to 8.5 MHz. A novel parabolic-amplitude four-section pulse is proposed, which can compensate the impact of the second echo optically, without using extra measurement time and post-processing. The key parameters of the proposed pulse are optimized by combining an upgraded mathematical model and the iterative algorithm. The experimental results show a good agreement with the analysis about the behavior of the second echo, and demonstrate that the proposed technique is capable of providing sub-meter spatial resolution and the natural linewidth of Brillouin gain spectrum simultaneously, while completely eliminating the impact of the second echo. PMID- 26832534 TI - Diffractive lenses recorded in absorbent photopolymers. AB - Photopolymers can be appealing materials for diffractive optical elements fabrication. In this paper, we present the recording of diffractive lenses in PVA/AA (Polyvinyl alcohol acrylamide) based photopolymers using a liquid crystal device as a master. In addition, we study the viability of using a diffusion model to simulate the lens formation in the material and to study the influence of the different parameters that govern the diffractive formation in photopolymers. Once we control the influence of each parameter, we can fit an optimum recording schedule to record each different diffractive optical element with the optimum focalization power. PMID- 26832535 TI - Optical coherence tomography system mass-producible on a silicon photonic chip. AB - Miniaturized integrated optical coherence tomography (OCT) systems have the potential to unlock a wide range of both medical and industrial applications. This applies in particular to multi-channel OCT schemes, where scalability and low cost per channel are important, to endoscopic implementations with stringent size demands, and to mechanically robust units for industrial applications. We demonstrate that fully integrated OCT systems can be realized using the state-of the-art silicon photonic device portfolio. We present two different implementations integrated on a silicon-on-insulator (SOI) photonic chip, one with an integrated reference path (OCTint) for imaging objects in distances of 5 mm to 10 mm from the chip edge, and another one with an external reference path (OCText) for use with conventional scan heads. Both OCT systems use integrated photodiodes and an external swept-frequency source. In our proof-of-concept experiments, we achieve a sensitivity of -64 dB (-53 dB for OCTint) and a dynamic range of 60 dB (53 dB for OCTint). The viability of the concept is demonstrated by imaging of biological and technical objects. PMID- 26832536 TI - Quasi-distributed birefringence dispersion measurement for polarization maintain device with high accuracy based on white light interferometry. AB - A white light temporal interferometric technique for measurement of the quasi distributed birefringence dispersion (BD) in a polarization maintain (PM) device with high accuracy based on weighted least square (WLS) method is presented. It is verified theoretically and experimentally that the accuracy of WLS method and the conventional ordinary least square (OLS) method both are proportional to the signal-to-noise ratio (SNR) of interferogram, whereas the WLS method holds a higher scaling factor because it is more suitable for heteroscedastic model that has unequal error variance. The experiment results show a repeatability of ~4.6 * 10(-5) ps/nm @ 1550 nm with WLS method for 100 sets of data, and ~4.3 * 10(-4) ps/nm with OLS method, for an interferogram with SNR of 30 dB. Besides, WLS method without iterative operation is carried out by using power spectrum of interferogram as weight value. The feasibility of this technique is demonstrated by distinguishing the quasi-distributed BD of every part for a packaged Y waveguide with two 1m-long PM pigtails. PMID- 26832537 TI - Multi-layered black phosphorus as saturable absorber for pulsed Cr:ZnSe laser at 2.4 MUm. AB - A high-quality black phosphorus (BP) saturable-absorber mirror (SAM) was successfully fabricated with the multi-layered BP, prepared by liquid-phase exfoliation (LPE) method. The modulation depth and saturation power intensity of BP absorber were measured to be 10.7% and 0.96 MW/cm(2), respectively. Using the BP-SAM, we experimentally demonstrated the mid-infrared (mid-IR) pulse generation from a BP Q-switched Cr:ZnSe laser for the first time to our best knowledge. Stable Q-switched pulse as short as 189 ns with an average output power of 36 mW was realized at 2.4 MUm, corresponding to a repetition rate of 176 kHz and a single pulse energy of 205 nJ. Our work sufficiently validated that multi-layer BP could be used as an optical modulator for mid-IR pulse laser sources. PMID- 26832538 TI - Spectral control of high-harmonic generation via drive laser pulse shaping in a wide-diameter capillary. AB - We experimentally investigate spectral control of high-harmonic generation in a wide-diameter (508 MUm) capillary that allows using significantly lower gas pressures coupled with elevated drive laser energies to achieve higher harmonic energies. Using phase shaping to change the linear chirp of the drive laser pulses, we observe wavelength tuning of the high-harmonic output to both larger and smaller values. Comparing tuning via the gas pressure with the amount of blue shift in the transmitted drive laser spectrum, we conclude that both adiabatic and non-adiabatic effects cause pulse-shaping induced tuning of high harmonics. We obtain a fractional wavelength tuning, Deltalambda/lambda, in the range from 0.007 to + 0.01, which is comparable to what is achieved with standard capillaries of smaller diameter and higher pressures. PMID- 26832539 TI - Multi-Watt mid-IR femtosecond polycrystalline Cr(2+):ZnS and Cr(2+):ZnSe laser amplifiers with the spectrum spanning 2.0-2.6 um. AB - We demonstrate efficient amplification of few-optical-cycle mid-IR pulses in single-pass continuously pumped laser amplifiers based on polycrystalline Cr(2+):ZnS and Cr(2+):ZnSe. The 1.7 W output of a Kerr-lens mode-locked master oscillator at 2.4 um central wavelength, 79 MHz repetition rate was amplified to 7.1 W and 2.7 W in Cr(2+):ZnS and Cr(2+):ZnSe, respectively. High peak power of the input pulses (0.5 MW) and high nonlinearity of the amplifiers' gain media resulted in a significant shortening of the output pulses and in spectral broadening. Transform-limited 40 fs pulses of the master oscillator were compressed to about 27-30 fs. The spectrum of the pulses was broadened from 136 nm to 450 nm (at -3 dB level); the span of the spectra exceeds 600 nm at -10 dB level. PMID- 26832540 TI - Optical design for single-mode and single-cell gap transflective liquid crystal displays. AB - Generally, for transflective liquid crystal displays with different modes and different cell gaps between the refractive and transmissive parts, precise process control to pattern the electrode and match the cell gaps may reduce the yield and thus, require high cost. This paper proposes a simple transflective liquid crystal display with a single-mode and single-cell thickness without a patterned electrode to achieve better productivity. The proposed transflective liquid crystal display consists of three half-wave retardation films, two quarter wave retardation films, and an LC layer, whose optical performance was confirmed by both simulation and experiment. The optimal optical configuration to obtain an excellent dark state in the visible range was determined by the Mueller matrices calculus, which was applied to each optical component. The calculated and experimental results showed that the proposed transflective LC structure has excellent electro-optical properties and is expected to have many liquid crystal display applications. PMID- 26832541 TI - Influence of optical forces on nonlinear optical frequency conversion in nanoscale waveguide devices. AB - We theoretically investigate the influence of optical gradient forces on nonlinear frequency conversion in a typical nanoscale optomechanical system, which consists of two parallel, suspended waveguides. The waveguides deform with the input power and the phase-matching wavelength changes along the waveguides. Utilizing the spread of deformations collectively allows phase matching over a wider range of pump wavelengths. The third harmonic phase-matching wavelength shift can be as large as 3.6 nm/mW when the waveguide length is 100 MUm and the initial gap is 150 nm. It is analogous to chirping the poling period of quasi phase-matched devices to extend their bandwidths, and allows broad third harmonic to be generated for uses such as biological spectroscopy. Finally, we discuss the conversion efficiency and the optimal phase-matching wavelength with a single frequency pump. PMID- 26832542 TI - Investigation of the extraordinary null reconstruction phenomenon in polarization volume hologram. AB - Polarization holography is the superposition of differently polarized beams. Due to its ability to record the polarization states, some extraordinary optical phenomena were found in the polarization holography. For example, the recently reported null-reconstruction phenomenon in polarization volume hologram is odd for the conventional holography which only records the amplitude and phase. In this paper, we perform a thorough investigation of the null reconstruction of polarization hologram recorded by orthogonal circularly polarized waves. To explore the mechanism behind this phenomenon, an interferometry was built to measure the phase difference between the same polarized components within the reconstructed wave. The phase difference of pi was secured in our experiment, indicating a destructive interfering effect, which nicely explains the extraordinary null reconstruction observed in the polarization hologram. PMID- 26832543 TI - Zero index metamaterials with PT symmetry in a waveguide system. AB - Inspired by the concept of parity-time symmetry, we propose a new waveguide system consisting of zero index metamaterials with an air gap. Based on analytical calculations and numerical simulations, we demonstrate that there are two exceptional points in such a system, which can induce unidirectional transparency. However, the introduced air gap could effectively manipulate the property of the waveguide system with PT symmetry. In particular, coherent perfect absorber-laser modes could be excited in PT broken phase, if a specific phase difference in the air gap is obtained. More interestingly, when Fabry-Perot resonances take place in the air gap, the PT symmetry property will be suppressed, i.e., the value of loss/gain could not affect transmission and reflection of the waveguide. As a result, perfect bidirectional transmission without reflection can occur in the waveguide system. PMID- 26832544 TI - Concentric vortex beam amplification: experiment and simulation. AB - The amplification of a 2 MUm concentric vortex beam in a Ho:YAG crystal rod amplifier is simulated and experimentally verified. Different concentric vortex beams are studied and the amplification results are compared with simulation. The integrity of the launched vortex beams is well maintained through the amplification process. Further discussions are provided to increase the gain as well as for power scaling. Due to the nature of Ho:YAG material and the geometry of the rod amplifier, our system shows potential of working as a power amplifier for vortex beams. PMID- 26832545 TI - Fast-response switchable lens for 3D and wearable displays. AB - We report a switchable lens in which a twisted nematic (TN) liquid crystal cell is utilized to control the input polarization. Different polarization state leads to different path length in the proposed optical system, which in turn results in different focal length. This type of switchable lens has advantages in fast response time, low operation voltage, and inherently lower chromatic aberration. Using a pixelated TN panel, we can create depth information to the selected pixels and thus add depth information to a 2D image. By cascading three such device structures together, we can generate 8 different focuses for 3D displays, wearable virtual/augmented reality, and other head mounted display devices. PMID- 26832546 TI - Experimental demonstration of deep frequency modulation interferometry. AB - Experiments for space and ground-based gravitational wave detectors often require a large dynamic range interferometric position readout of test masses with 1 pm/?Hz precision over long time scales. Heterodyne interferometer schemes that achieve such precisions are available, but they require complex optical set-ups, limiting their scalability for multiple channels. This article presents the first experimental results on deep frequency modulation interferometry, a new technique that combines sinusoidal laser frequency modulation in unequal arm length interferometers with a non-linear fit algorithm. We have tested the technique in a Michelson and a Mach-Zehnder Interferometer topology, respectively, demonstrated continuous phase tracking of a moving mirror and achieved a performance equivalent to a displacement sensitivity of 250 pm/Hz at 1 mHz between the phase measurements of two photodetectors monitoring the same optical signal. By performing time series fitting of the extracted interference signals, we measured that the linearity of the laser frequency modulation is on the order of 2% for the laser source used. PMID- 26832547 TI - Sub-picosecond regenerative amplifier of Yb-doped Y(2)O(3) ceramic thin disk. AB - We have developed a 1 kHz regenerative amplifier using an Yb:Y(2)O(3) ceramic thin disk as the gain medium. Furthermore, the thermal conductivity and heat generation property of Yb:Y(2)O(3) ceramic were investigated. In the developed regenerative amplifier, a laser beam is bounced off the thin disk six times in each round trip. The output energy is over 2 mJ, spectral bandwidth is 1.8 nm at FWHM, and pulse duration after pulse compression is 0.9 ps. PMID- 26832548 TI - Phase noise in collective binary phase shift keying with Hadamard words. AB - We analyze the effect of phase fluctuations in an optical communication scheme based on collective detection of sequences of binary coherent state symbols using linear optics and photon counting. When the phase noise is absent, the scheme offers qualitatively improved nonlinear scaling of the spectral efficiency with the mean photon number in the low-power regime compared to individual detection. We show that this feature, providing a demonstration of superaddivitity of accessible information in classical communication over quantum channels, is preserved if random phases imprinted on transmitted symbols fluctuate around a reference fixed over the sequence length. PMID- 26832549 TI - Investigation of temperature sensing characteristics in selectively infiltrated photonic crystal fiber. AB - In this paper, we investigate and experimentally demonstrate the influences of distance between the silica core and the glycerin core of a selectively glycerin infiltrated photonic crystal fiber (PCF) on the mode characteristics, as well as the temperature sensitivity. By comparing the simulation and experiment results of three single-void glycerin-infiltrated PCFs with the glycerin core being one period, two periods and three periods away from the silica core respectively, it reveals that the smaller distance between the silica core and the glycerin core does not affect the modes indices, but increases the intensities of modes in the glycerin core and thus enhances the temperature sensitivity. Consequently, the temperature sensitivity can be controlled and tuned by appropriately designing the structure parameters of glycerin-infiltrated PCF. Besides, the highest temperature sensitivity up to -3.06nm/ degrees C is obtained in the experiment as the glycerin core is nearest to the silica core. This work provides insights into the design and optimization of the liquid-infiltrated PCF for sensing applications. PMID- 26832550 TI - Characterizing coated paper surface for modeling apparent dot area of halftone prints. AB - A new model is proposed for predicting the apparent dot area of simulated halftone prints on coated paper surface without requiring printing. It is based on Hotelling's multivariate T(2) statistic which is shown to provide a measure of lateral light scattering. The T(2) statistic is computed from colorimetric coordinates obtained from of a knife shadow image response on the paper surface. The proposed method offers superior prediction of halftone dot area compared to current light scattering models. A method for characterising peaks on the coated paper surface is introduced in this work. The effect of the paper coating layer thickness and the surface peak height on lateral light scattering and printed dot size are shown. PMID- 26832551 TI - Calibration-free wavelength-modulation spectroscopy based on a swiftly determined wavelength-modulation frequency response function of a DFB laser. AB - A methodology for calibration-free wavelength modulation spectroscopy (CF-WMS) that is based upon an extensive empirical description of the wavelength modulation frequency response (WMFR) of DFB laser is presented. An assessment of the WMFR of a DFB laser by the use of an etalon confirms that it consists of two parts: a 1st harmonic component with an amplitude that is linear with the sweep and a nonlinear 2nd harmonic component with a constant amplitude. Simulations show that, among the various factors that affect the line shape of a background subtracted peak-normalized 2f signal, such as concentration, phase shifts between intensity modulation and frequency modulation, and WMFR, only the last factor has a decisive impact. Based on this and to avoid the impractical use of an etalon, a novel method to pre-determine the parameters of the WMFR by fitting to a background-subtracted peak-normalized 2f signal has been developed. The accuracy of the new scheme to determine the WMFR is demonstrated and compared with that of conventional methods in CF-WMS by detection of trace acetylene. The results show that the new method provides a four times smaller fitting error than the conventional methods and retrieves concentration more accurately. PMID- 26832552 TI - Decryption with incomplete cyphertext and multiple-information encryption in phase space. AB - Recently, we have demonstrated that information encryption in phase space offers security enhancement over the traditional encryption schemes operating in real space. However, there is also an important issue with this technique: increasing the cost for data transmitting and storage. To address this issue, here we investigate the problem of decryption using incomplete cyphertext. We show that the analytic solution under the traditional framework set the lower limit of decryption performance. More importantly, we demonstrate that one just needs a small amount of cyphertext to recover the plaintext signal faithfully using compressive sensing, meaning that the amount of data that needs to transmit and store can be significantly reduced. This leads to multiple information encryption so that we can use the system bandwidth more effectively. We also provide an optical experimental result to demonstrate the plaintext recovered in phase space. PMID- 26832553 TI - Plasmonic microcavity using photo-reduced silver nanoparticles and light-emitting polymer. AB - We report a plasmonic Fabry-Perot (F-P) microcavity with silver nanoparticles and a continuous silver film function as the end mirrors, where the silver nanoparticles were produced through photo-reduction. Filled with a layer of light emitting polymer, the F-P microcavity becomes an active device with its output spectrum dependent on localized surface plasmon resonance (LSPR) of silver nanoparticles. A phase shift as large as pi is resolved in the resonance modes of the F-P microcavity due to the modulation by LSPR. This leads to complementary spectroscopic performance in the output of the plasmonic microcavity with respect to its non-plasmonic counterparts. PMID- 26832554 TI - Kilowatt-level direct-'refractive index matching liquid'-cooled Nd:YLF thin disk laser resonator. AB - A direct-liquid-cooled Nd:YLF thin disk laser resonator is presented, which features the use of refractive index matching liquid (RIML) as coolant. Highly uniform pump intensity distribution with rectangular shape is realized by using metallic planar waveguides. Much attention has been paid on the design of the gain module, including how to achieve excellent cooling ability with multi channel coolers and how to choose the doping levels of the crystals for realizing well-distributed pump absorption. The flow velocity of the coolant is found to be a key parameter for laser performance and optimized to keep it in laminar flow status for dissipating unwanted heat load. A single channel device is used to measure the convective heat transfer coefficient (CHTC) at different flow velocities. Accordingly, the thermal stress in the disk is analyzed numerically and the maximum permissible thermal load is estimated. Experimentally, with ten pieces of a-cut Nd:YLF thin disks of different doping levels, a linear polarized laser with an average output power of 1120 W is achieved at the pump power of 5202 W, corresponding to an optical-optical efficiency of 21.5%, and a slope efficiency of 30.8%. Furthermore, the wavefront aberration of the gain module is measured to be quite weak, with a peak to valley (PV) value of 4.0 MUm when it is pumped at 5202 W, which enables the feasibility of its application in an unstable resonator. To the best of our knowledge, this is the first demonstration of kilowatt-level direct-'refractive index matching liquid'-cooled Nd:YLF thin disk laser resonator. PMID- 26832555 TI - Silicon microring refractometric sensor for atmospheric CO(2) gas monitoring. AB - We report a silicon photonic refractometric CO(2) gas sensor operating at room temperature and capable of detecting CO(2) gas at atmospheric concentrations. The sensor uses a novel functional material layer based on a guanidine polymer derivative, which is shown to exhibit reversible refractive index change upon absorption and release of CO(2) gas molecules, and does not require the presence of humidity to operate. By functionalizing a silicon microring resonator with a thin layer of the polymer, we could detect CO(2) gas concentrations in the 0 500ppm range with a sensitivity of 6 * 10(-9) RIU/ppm and a detection limit of 20ppm. The microring transducer provides a potential integrated solution in the development of low-cost and compact CO(2) sensors that can be deployed as part of a sensor network for accurate environmental monitoring of greenhouse gases. PMID- 26832556 TI - Iterative re-weighted approach to high-resolution optical coherence tomography with narrow-band sources. AB - Optical coherence tomography (OCT) is a non-invasive optical imaging modality capable of high resolution imaging of internal tissue structures. It is widely believed that the high axial resolution in OCT systems requires a wide-bandwidth light source. As a result, often the potential advantages of narrow-bandwidth sources (in terms of cost and/or imaging speed) are understood to come at the cost of significant reduction in imaging resolution. In this paper, we argue that this trade-off between resolution and speed is a shortcoming imposed by the-state of-the-art A-scan reconstruction algorithm, Fast Fourier Transform, and can be circumvented through use of alternative processing methods. In particular, we investigate the shortcomings of the FFT as well as previously proposed alternatives and demonstrate the first application of an iterative regularized re weighted l(2) norm method to improve the axial resolution of fast scan rate OCT systems in the narrow-bandwidth imaging conditions. We validate our claims via experimental results generated from a home-built OCT system used to image layered phantom and in vivo data. Our results rely on new, sophisticated signal processing algorithms to generate higher precision (i.e., higher resolution) OCT images at correspondingly fast scan rates. In other words, our work demonstrates the feasibility of simultaneously more reliable and more comfortable medical imaging systems for patients by reducing the overall scan time, without sacrificing image quality. PMID- 26832557 TI - Resonant absorption and amplification of circularly-polarized waves in inhomogeneous chiral media. AB - It has been found that in the media where the dielectric permittivity epsilon or the magnetic permeability MU is near zero and in transition metamaterials where epsilon or MU changes from positive to negative values, there occur a strong absorption or amplification of the electromagnetic wave energy in the presence of an infinitesimally small damping or gain and a strong enhancement of the electromagnetic fields. We attribute these phenomena to the mode conversion of transverse electromagnetic waves into longitudinal plasma oscillations and its inverse process. In this paper, we study analogous phenomena occurring in chiral media theoretically using the invariant imbedding method. In uniform isotropic chiral media, right-circularly-polarized and left-circularly-polarized waves are the eigen-modes of propagation with different effective refractive indices n(+) and n(-), whereas in the chiral media with a nonuniform impedance variation, they are no longer the eigenmodes and are coupled to each other. We find that both in uniform chiral slabs where either n(+) or n(-) is near zero and in chiral transition metamaterials where n(+) or n(-) changes from positive to negative values, a strong absorption or amplification of circularly-polarized waves occurs in the presence of an infinitesimally small damping or gain. We present detailed calculations of the mode conversion coefficient, which measures the fraction of the electromagnetic wave energy absorbed into the medium, for various configurations of epsilon and MU with an emphasis on the influence of a nonuniform impedance. We propose possible applications of these phenomena to linear and nonlinear optical devices that react selectively to the helicity of the circular polarization. PMID- 26832558 TI - Propagation factors of multi-sinc Schell-model beams in non-Kolmogorov turbulence. AB - We derive several analytical expressions for the root-mean-square (rms) angular width and the M(2)-factor of the multi-sinc Schell-model (MSSM) beams propagating in non-Kolmogorov turbulence with the extended Huygens-Fresnel principle and the second-order moments of the Wigner distribution function. Numerical results show that a MSSM beam with dark-hollow far fields in free space has advantage over the one with flat-topped or multi-rings far fields for reducing the turbulence induced degradation, which will become more obvious with larger dark-hollow size. Beam quality of MSSM beams can be further improved with longer wavelength and larger beam width, or under the condition of weaker turbulence. We also demonstrate that the non-Kolmogorov turbulence has significantly less effect on the MSSM beams than the Gaussian Schell-model beam. PMID- 26832559 TI - Coexistence and interaction of vector and bound vector solitons in a dispersion managed fiber laser mode locked by graphene. AB - We report on the experimental observation of vector and bound vector solitons in a fiber laser passively mode locked by graphene. Localized interactions between vector solitons, vector soliton with bound vector solitons, and vector soliton with a bunch of vector solitons are experimentally investigated. We show that depending on the soliton interactions, various stable and dynamic multiple vector soliton states could be formed. PMID- 26832560 TI - Spectrally efficient polarization multiplexed direct-detection OFDM system without frequency gap. AB - We experimentally demonstrate a spectrally efficient direct-detection orthogonal frequency-division multiplexing (DD-OFDM) system. In addition to polarization division multiplexing, removing the frequency gap further improves the spectral efficiency of the OFDM system. The frequency gap between a reference carrier and OFDM subcarriers avoids subcarrier-to-subcarrier beating interference (SSBI) in traditional DD-OFDM systems. Without dynamic polarization control, the resulting interference after square-law direct detection in the proposed gap-less system is polarization-dependent and composed of linear inter-carrier interference (ICI) and nonlinear SSBI. Thus, this work proposes an iterative multiple-input multiple output detection scheme to remove the mixed polarization-dependent interference. Compared to the previous scheme, which only removes ICI, the proposed scheme can further eliminate SSBI to achieve the improvement of ~ 7 dB in signal-to-noise ratio. Without the need for polarization control, we successfully utilize 7-GHz bandwidth to transmit a 39.5-Gbps polarization multiplexed OFDM signal over 100 km. PMID- 26832561 TI - Concerning the Spatial Heterodyne Spectrometer. AB - A modified Spatial Heterodyne Spectrometer (SHS) is used for measuring atomic emission spectra with high resolution. This device is basically a Fourier Transform Spectrometer, but the Fourier transform is taken in the directions perpendicular to the optical propagation and heterodyned around one preset wavelength. In recent descriptions of this device, one specific phenomenon - the tilt of the energy front of wave packets when diffracted from a grating - was neglected. This led to an overestimate of the resolving power of this spectrograph, especially in situations when the coherence length of the radiation under test is in the order of the effective aperture of the device. The limits of usability are shown here together with some measurements of known spectral lines. PMID- 26832562 TI - Holography-guided ptychography with soft X-rays. AB - Ptychography is a lensless imaging technique that aims to reconstruct an object from a set of coherent diffraction patterns originating from different and partially overlapping sample illumination areas. For a successful convergence of the iterative algorithms used, the sample scan positions have to be known with very high accuracy. Here, we present a method that allows to directly encode this information in the diffraction patterns without the need of accurate position encoders. Our approach relies on combining ptychography with another coherent imaging method, namely Fourier-transform holography. We have imaged two different objects using coherent soft-X-ray illumination and investigate the influence of experimental and numerical position refinement on the reconstruction result. We demonstrate that holographically encoded positions significantly reduce the experimental and numerical requirements. Our ptychographic reconstructions cover a large field of view with diffraction-limited resolution and high sensitivity in the reconstructed phase shift and absorption of the objects. PMID- 26832563 TI - Quantitative filter technique measurements of spectral light absorption by aquatic particles using a portable integrating cavity absorption meter (QFT ICAM). AB - The accurate determination of light absorption coefficients of particles in water, especially in very oligotrophic oceanic areas, is still a challenging task. Concentrating aquatic particles on a glass fiber filter and using the Quantitative Filter Technique (QFT) is a common practice. Its routine application is limited by the necessary use of high performance spectrophotometers, distinct problems induced by the strong scattering of the filters and artifacts induced by freezing and storing samples. Measurements of the sample inside a large integrating sphere reduce scattering effects and direct field measurements avoid artifacts due to sample preservation. A small, portable, Integrating Cavity Absorption Meter setup (QFT-ICAM) is presented, that allows rapid measurements of a sample filter. The measurement technique takes into account artifacts due to chlorophyll-a fluorescence. The QFT-ICAM is shown to be highly comparable to similar measurements in laboratory spectrophotometers, in terms of accuracy, precision, and path length amplification effects. No spectral artifacts were observed when compared to measurement of samples in suspension, whereas freezing and storing of sample filters induced small losses of water-soluble pigments (probably phycoerythrins). Remaining problems in determining the particulate absorption coefficient with the QFT-ICAM are strong sample-to-sample variations of the path length amplification, as well as fluorescence by pigments that is emitted in a different spectral region than that of chlorophyll-a. PMID- 26832564 TI - Inherent optical properties of pollen particles: a case study for the morning glory pollen. AB - Biological aerosols, such as bacteria, fungal spores, and pollens, play an important role on various atmospheric processes, whereas their inherent optical property is one of the most uncertainties that limit our ability to assess their effects on weather and climate. A numerical model with core-shell structure, hexagonal grids and barbs is developed to represent one kind of realistic pollen particles, and their inherent optical properties are simulated using a pseudo spectral time domain method. Both the hexagonal grids and barbs substantially affect the modeled pollen optical properties. Results based on the realistic particle model are compared with two equivalent spherical approximations, and the significant differences indicate the importance of considering pollen geometries for their optical properties. PMID- 26832565 TI - Fabrication and characterization of on-chip silicon nitride microdisk integrated with colloidal quantum dots. AB - We designed and fabricated free-standing, waveguide-coupled silicon nitride microdisks hybridly integrated with embedded colloidal quantum dots. An efficient coupling of quantum dot emission to resonant disk modes and eventually to the access waveguides is demonstrated. The amount of light coupled out to the access waveguide can be tuned by controlling its dimensions and offset with the disk edge. These devices open up new opportunities for both on-chip silicon nitride integrated photonics and novel optoelectronic devices with quantum dots. PMID- 26832566 TI - Distance within colloidal dimers probed by rotation-induced oscillations of scattered light. AB - Aggregation processes of colloidal particles are of broad scientific and technological relevance. The earliest stage of aggregation, when dimers appear in an ensemble of single particles, is very important to characterize because it opens routes for further aggregation processes. Furthermore, it represents the most sensitive phase of diagnostic aggregation assays. Here, we characterize dimers by rotating them in a magnetic field and by recording the angle dependence of light scattering. At small scattering angles, the scattering cross section can be approximated by the total cross-sectional area of the dimer. In contrast, at scattering angles around 90 degrees, we reveal that the dependence of the scattering cross section on the dimer angle shows a series of peaks per single 2pi rotation of the dimers. These characteristics originate from optical interactions between the two particles, as we have verified with two-particle Mie scattering simulations. We have studied in detail the angular positions of the peaks. It appears from simulations that the influence of particle size polydispersity, Brownian rotation and refractive index on the angular positions of the peaks is relatively small. However, the angular positions of the peaks strongly depend on the distance between the particles. We find a good correspondence between measured data and calculations for a gap of 180 nm between particles having a diameter of 1 micrometer. The experiment and simulations pave the way for extracting distance-specific data from ensembles of dimerizing colloidal particles, with application for sensitive diagnostic aggregation assays. PMID- 26832567 TI - Smart multifunction diffractive lens experimental validation for future PV cell applications. AB - Recently, diffractive optical elements (DOE's) have attracted more attention for applications to third generation PV cells. Some DOE types can provide multiple functions such as spectrum splitting and beam concentration (SSBC) simultaneously. An off-axis diffractive lens has been designed and its ability to achieve the SSBC proved experimentally. This lens can be used to separate the solar spectrum in the Vis-NIR range into two bands with a low concentration factor, and about 70% optical efficiency. It is expected that this kind of lens can be integrated with the lateral multijunction PV cells to build an effective compact solar system. PMID- 26832568 TI - CdS(x)Se(1-x)/ZnS semiconductor nanocrystal laser with sub 10kW/cm(2) threshold and 40nJ emission output at 600 nm. AB - A colloidal quantum dot laser emitting at 600 nm with a sub 10kW/cm(2) threshold at 5ns pulse pumping is reported. The device has a second order distributed feedback cavity for vertical emission and incorporates a bilayer planar waveguide structure based on a film of yellow-orange alloyed-core/shell CdS(x)Se(1-x)/ZnS quantum dots over-coated with polyvinyl alcohol. A study of the amplified spontaneous regime indicates that the quantum dot gain region behaves like a quasi-three level system and that the bilayer structure design increases the modal gain compared to a single layer of quantum dots. An output of 40nJ per pulse is measured for a total pump-to-signal efficiency above threshold of 3%. PMID- 26832569 TI - Third-order nonlinear optical properties of colloidal Au nanorods systems: saturable and reverse-saturable absorption. AB - In this work, we present a study of the nonlinear absorption properties from different gold nanorod (NR) systems in aqueous suspension. The NRs were obtained with the bottom-up protocol by the seed-mediated growth method (SMG), using Ag(+) ions at different concentrations, and CTAB as surfactant. By using this method, aspect ratios between 2 and 5 were obtained. The transverse surface plasmons (TSP) are located between 514 - 535 nm, while the longitudinal surface plasmons (LSP) are between 639 - 921 nm, for the different samples studied. The Z-scan technique was implemented for open (OA) and closed (CA) aperture at 532 and 1064 nm, with laser pulses of 26 ps, for vertical and horizontal polarizations, with respect to the incidence plane (horizontal). At 532 nm all samples showed saturable absorption (SA), while for samples with LSP near 1064 nm, such effect was observed only at low-energy pulse experimental conditions. In the high-energy pulse regime, an apparent reverse-saturable absorption (RSA) was observed for both wavelengths. However for 532 nm, it was possible to determine that this effect results from structural changes in the samples, which are manifested through the behavior of nonlinear absorption and refraction curves. These results were used to determine the irradiances to which NRs can be modified by photodegradation. PMID- 26832570 TI - Enhanced Raman scattering of ZnO nanocrystals in the vicinity of gold and silver nanostructured surfaces. AB - nonresonant surface enhanced Raman scattering by optical phonons of ZnO nanocrystals on and beneath silver and gold island films is reported. For both configurations comparable SERS efficiency is observed, proving their potential utility. Variations in peak intensities can be attributed to difference in the morphology of island films on and beneath nanocrystals as well as to variation of the interface between semiconductor and metal. The dominant peaks in the SERS spectra are assigned to surface optical phonon modes. PMID- 26832571 TI - Nanoplasmonic Raman detection of bromate in water. AB - The possibility of using surface enhanced Raman scattering (SERS) detection method for bromate-anion determination and quantitative evaluation in water has been demonstrated for the first time. The decreasing of Rhodamine 6G (R6G) Raman peaks intensity has been used as the analytical signal corresponding to the catalytic oxidation by bromate. Electrostatically immobilized silver nanoparticles have been proven as efficient SERS-active substrate. A linear relationship between the Raman intensity of Rh6G as a function of BrO(3)(-) was observed in the range of 0 - 10(-7) M and the detect limit was as low as 10(-10) M (nearly 0.01 MUg/L). The results prove the potential of the proposed method for further application in the development of new portable SERS-based sensors for drinking water monitoring with high sensitivity, simplicity and the low cost. PMID- 26832572 TI - Microfluidic device for continuous single cells analysis via Raman spectroscopy enhanced by integrated plasmonic nanodimers. AB - In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels- where the cells can flow one-by-one -, allowing single cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm of the each cell. Experiments are performed on red blood cells (RBCs), peripheral blood lymphocytes (PBLs) and myelogenous leukemia tumor cells (K562). PMID- 26832573 TI - Disordered nanostructures by hole-mask colloidal lithography for advanced light trapping in silicon solar cells. AB - We report on the fabrication of disordered nanostructures by combining colloidal lithography and silicon etching. We show good control of the short-range ordered colloidal pattern for a wide range of bead sizes from 170 to 850 nm. The inter particle spacing follows a Gaussian distribution with the average distance between two neighboring beads (center to center) being approximately twice their diameter, thus enabling the nanopatterning with dimensions relevant to the light wavelength scale. The disordered nanostructures result in a lower integrated reflectance (8.1%) than state-of-the-art random pyramid texturing (11.7%) when fabricated on 700 um thick wafers. When integrated in a 1.1 um thin crystalline silicon slab, the absorption is enhanced from 24.0% up to 64.3%. The broadening of resonant modes present for the disordered nanopattern offers a more broadband light confinement compared to a periodic nanopattern. Owing to its simplicity, versatility and the degrees of freedom it offers, this potentially low-cost bottom-up nanopatterning process opens perspectives towards the integration of advanced light-trapping schemes in thin solar cells. PMID- 26832574 TI - Electromagnetic resonance modes on a two-dimensional tandem grating and its application for broadband absorption in the visible spectrum. AB - In this work, we numerically investigate the electromagnetic resonances on two dimensional tandem grating structures. The base of a tandem grating consists of an opaque Au substrate, a SiO(2) spacer, and a Au grating (concave type); that is, a well-known fishnet structure forming Au/SiO(2)/Au stack. A convex-type Au grating (i.e., topmost grating) is then attached on top of the base fishnet structure with or without additional SiO(2) spacer, resulting in two types of tandem grating structures. In order to calculate the spectral reflectance and local magnetic field distribution, the finite-difference time-domain method is employed. When the topmost Au grating is directly added onto the base fishnet structure, the surface plasmon and magnetic polariton in the base structure are branched out due to the geometric asymmetry with respect to the SiO(2) spacer. If additional SiO(2) spacer is added between the topmost Au grating and the base fishnet structure, new magnetic resonance modes appear due to coupling between two vertically aligned Au/SiO(2)/Au stacks. With the understanding of multiple electromagnetic resonance modes on the proposed tandem grating structures, we successfully design a broadband absorber made of Au and SiO(2) in the visible spectrum. PMID- 26832575 TI - Cloaking by shells with radially inhomogeneous anisotropic permittivity. AB - We model electromagnetic cloaking of a spherical or cylindrical nanoparticle enclosed by an optically anisotropic and optically inhomogeneous symmetric shell, by examining its electric response in a quasi-static uniform electric field. When the components of the shell permittivity are radially anisotropic and power-law dependent (epsilon~r(m)) whereris distance to the shell center, and m a positive or negative exponent which can be varied), the problem is analytically tractable. Formulas are calculated for the degree of cloaking in the general case, allowing the determination of a dielectric condition for the shells to be used as an invisibility cloak. Ideal cloaking is known to require that homogeneous shells exhibit an infinite ratio of tangential and radial components of the shell permittivity, but for radially inhomogeneous shells ideal cloaking can occur even for finite values of this ratio. PMID- 26832576 TI - High luminous flux from single crystal phosphor-converted laser-based white lighting system. AB - The efficiency droop of light emitting diodes (LEDs) with increasing current density limits the amount of light emitted per wafer area. Since low current densities are required for high efficiency operation, many LED die are needed for high power white light illumination systems. In contrast, the carrier density of laser diodes (LDs) clamps at threshold, so the efficiency of LDs does not droop above threshold and high efficiencies can be achieved at very high current densities. The use of a high power blue GaN-based LD coupled with a single crystal Ce-doped yttrium aluminum garnet (YAG:Ce) sample was investigated for white light illumination applications. Under CW operation, a single phosphor converted LD (pc-LD) die produced a peak luminous efficacy of 86.7 lm/W at 1.4 A and 4.24 V and a peak luminous flux of 1100 lm at 3.0 A and 4.85 V with a luminous efficacy of 75.6 lm/W. Simulations of a pc-LD confirm that the single crystal YAG:Ce sample did not experience thermal quenching at peak LD operating efficiency. These results show that a single pc-LD die is capable of emitting enough luminous flux for use in a high power white light illumination system. PMID- 26832577 TI - Efficiency enhancement in two-cell CIGS photovoltaic system with low-cost optical spectral splitter. AB - Spectrum splitting represents a valid alternative to multi-junction solar cells for broadband light-to-electricity conversion. While this concept has existed for decades, its adoption at the industrial scale is still stifled by high manufacturing costs and inability to scale to large areas. Here we report the experimental validation of a novel design that could allow the widespread adoption of spectrum splitting as a low-cost approach to high efficiency photovoltaic conversion. Our system consists of a prismatic lens that can be manufactured using the same methods employed for conventional CPV optic production, and two inexpensive CuInGaSe(2) (CIGS) solar cells having different composition and, thus, band gaps. We demonstrate a large improvement in cell efficiency under the splitter and show how this can lead to substantial increases in system output at competitive cost using existing technologies. PMID- 26832578 TI - Laboratory experiments for inter-comparison of three volume scattering meters to measure angular scattering properties of hydrosols. AB - Measurements of the volume scattering function (VSF) of hydrosols is of primary importance to investigate the interaction of light with hydrosols and to further interpret in situ and remote sensing data of ocean color. In this paper, a laboratory inter-comparison experiment of three recently developed VSF meters that are able to measure the scattered light for a wide range of scattering angle at 515 nm wavelength is performed using phytoplankton cultures and mineral-like hydrosols. A rigorous measurement protocol was employed to ensure good quality data. In particular, the protocol enabled removing the influence of bacteria on the hydrosols within the sample. The differences in the VSF measurements between the instruments vary from 10 to 25% depending on the composition of the hydrosols. The analysis of the angular features of the VSF revealed a sharp increase of the VSF beyond the scattering angle of 150 degrees for some phytoplankton species. Such behavior is observed for two of the three VSF meters, thus suggesting that it is not due to instrumental artifacts but more likely to phytoplankton optical properties themselves. Moreover, comparisons with currently used theoretical phase functions show that the models are not able to reproduce satisfactorily the directional patterns in the backscattering region. This study suggests that a better modelling of the VSF shape of phytoplankton at high scattering angles is required to correctly represent the angular shape of the VSF in the backscattering hemisphere. Tabulated values of the measured phase functions are provided for scattering angles from 0.1 to 175 degrees . PMID- 26832579 TI - Land surface temperature retrieved from airborne multispectral scanner mid infrared and thermal-infrared data. AB - Land surface temperature (LST) is one of the key parameters in the physics of land surface processes at local/global scales. In this paper, a LST retrieval method was proposed from airborne multispectral scanner data comparing one mid infrared (MIR) channel and one thermal infrared (TIR) channel with the land surface emissivity given as a priori knowledge. To remove the influence of the direct solar radiance efficiently, a relationship between the direct solar radiance and water vapor content and the view zenith angle and solar zenith angle was established. Then, LST could be retrieved with a split-window algorithm from MIR/TIR data. Finally, the proposed algorithm was applied to the actual airborne flight data and validated with in situ measurements of land surface types in the Baotou site in China on 17 October 2014. The results demonstrate that the difference between the retrieved and in situ LST was less than 1.5 K. The bais, RMSE, and standard deviation of the retrieved LST were 0.156 K, 0.883 K, and 0.869 K, respectively, for samples. PMID- 26832580 TI - Control of the IR-spectral shift via modification of the surface relief between the liquid crystal matrixes doped with the lanthanide nanoparticles and the solid substrate. AB - The influence of the surface nanostructured relief on the near IR-spectral shift and on the structural properties of the nematic liquid crystal (NLC) materials doped with nanoparticles from lanthanide group has been considered. The relief mentioned above has been made on the interface between glass substrate with ITO coatings and the LC mesophase. The specific feature of this relief is based on the applying of the contactless laser deposition technique and on the its modification by using surface electromagnetic waves (SEW) or carbon nanotubes (CNTs) treated with SEW. The modified relief permits to orient LC molecules without direct polymer orienting layers and can be used as conducting layer too. The features mentioned above lead to decrease drastically the resistivity and the bias voltage as well as that permits to increase the transparency and reveal the near IR-shift in the spectral characteristics of the lanthanide-doped LC mesophase. PMID- 26832581 TI - Designing unit cell in three-dimensional periodic nanostructures using colloidal lithography. AB - Colloidal phase-shift lithography, the illumination of a two-dimensional (2D) ordered array of self-assembled colloidal nanospheres, is an effective method for the fabrication of periodic three-dimensional (3D) nanostructures. In this work, we investigate the design and control of the unit-cell geometry by examining the relative ratio of the illumination wavelength and colloidal nanosphere diameter. Using analytical and finite-difference time-domain (FDTD) modeling, we examine the effect of the wavelength-diameter ratio on intensity pattern, lattice constants, and unit-cell geometry. These models were validated by experimental fabrication for various combination of wavelength and colloid diameter. The developed models and fabrication tools can facilitate the design and engineering of 3D periodic nanostructure for photonic crystals, volumetric electrodes, and porous materials. PMID- 26832582 TI - Organic-inorganic and all-inorganic lead halide nanoparticles [Invited]. AB - Organic-inorganic (hybrid) and all-inorganic lead halide perovskites, in particular APbX(3) where A is an organic cation (methylammonium or formamidinium) or cesium cation and X = Cl, Br, I, respectively, are of great interest in photovoltaic devices and as luminescent materials for light-emitting devices. It has recently been demonstrated that they can be prepared not only as nanoparticulate material by using the pores of mesoporous films, but also as colloidal nanoparticles, which exhibit enhanced optical properties with respect to the bulk material. We summarize here the methods reported for their preparation as well as their optical features. Experimental and theoretical studies on this class of materials are ongoing and there is still a demand for enhancing their emissive properties, stability in polar solvents, dispersibility in different media and/or photostability. PMID- 26832583 TI - Visible-to-visible four-photon ultrahigh resolution microscopic imaging with 730 nm diode laser excited nanocrystals. AB - Further development of multiphoton microscopic imaging is confronted with a number of limitations, including high-cost, high complexity and relatively low spatial resolution due to the long excitation wavelength. To overcome these problems, for the first time, we propose visible-to-visible four-photon ultrahigh resolution microscopic imaging by using a common cost-effective 730-nm laser diode to excite the prepared Nd(3+)-sensitized upconversion nanoparticles (Nd(3+) UCNPs). An ordinary multiphoton scanning microscope system was built using a visible CW diode laser and the lateral imaging resolution as high as 161-nm was achieved via the four-photon upconversion process. The demonstrated large saturation excitation power for Nd(3+)-UCNPs would be more practical and facilitate the four-photon imaging in the application. A sample with fine structure was imaged to demonstrate the advantages of visible-to-visible four photon ultrahigh resolution microscopic imaging with 730-nm diode laser excited nanocrystals. Combining the uniqueness of UCNPs, the proposed visible-to-visible four-photon imaging would be highly promising and attractive in the field of multiphoton imaging. PMID- 26832584 TI - Luminescent colloidal carbon dots: optical properties and effects of doping [Invited]. AB - We review the effect of doping on the optical properties of luminescent colloidal carbon dots. They are considered as a hybrid material featuring both molecular and semiconductor-like characteristics, where doping plays an important role. Starting from the short overview of synthetic strategies, we consider the evolution of carbon dots from molecular precursors to fluorescent nanoparticles, and the relevant structural properties of carbon dots. Choice of the reactant materials, dopant atoms and reaction parameters provide carbon dots with varying optical properties. High chemical stability, bright luminescence and customizable surface functionalization of carbon dots open their use in a broad range of applications, which are exemplary presented at the end of this review. PMID- 26832585 TI - Surface plasmon-enhanced quantum dot light-emitting diodes by incorporating gold nanoparticles. AB - Surface plasmon-enhanced electroluminescence (EL) has been demonstrated by incorporating gold (Au) nanoparticles (NPs) in quantum dot light-emitting diode (QLED). Time-resolved photoluminescence (TRPL) spectroscopy reveals that the EL enhancement is ascribed to the near-field enhancement through an effective coupling between excitons of the quantum dot emitters and localized surface plasmons around Au NPs. It is found that the size of Au NPs and the distance between the Au NPs and the emissive layer have significant effects on the performance of QLED. The enhancement can be maximized as the SP resonance wavelength of Au NPs matches well with the PL emission wavelength of the QD film and the distance between Au NPs and the emissive layer maintains 15 nm. The photoluminance (PL) and EL intensity can be enhanced by 4.4 and 1.7 folds with the incorporation of Au NPs. The maximum current efficiency of 4.56 cd/A can be achieved for the resulting QLEDs by incorprating Au NPs with an enhancement factor of 2.0. In addition, the enhancement ratio of 2.2 can be achieved for the lifetime of resulting QLED. PMID- 26832586 TI - Improvement of light quality by ZrO(2) film of chip on glass structure white LED. AB - A novel combination of blue LED chips, transparent glass substrates and phosphors with PDMS thin film is demonstrated. The flip-chip bonding technology is applied to facilitate this design. The ZrO(2) nanoparticles are also doped into the PDMS film to increase light scattering. The resultant luminous efficiency shows an 11% enhancement when compared to the regular COG device. The variation of correlated color temperature of such devices is also reduced to 132K. In addition to these changes, the surface temperature is reduced from 121 degrees C to 104 degrees C due to good thermal dissipation brought by ZrO(2) nanoparticles. PMID- 26832587 TI - Microstructural and optical properties of CdSe/CdS/ZnS core-shell-shell quantum dots. AB - CdSe/CdS/ZnS core-shell-shell quantum dots (QDs) were synthesized by using a solution process. High-resolution transmission electron microscopy images and energy dispersive spectroscopy profiles confirmed that stoichiometric CdSe/CdS/ZnS core-shell-shell QDs were formed. Ultraviolet-visible absorption and photoluminescence (PL) spectra of CdSe/CdS/ZnS core-shell-shell QDs showed the dominant excitonic transitions from the ground electronic subband to the ground hole subband (1S(e)-1S(3/2)(h)). The PL mechanism is suggested; the carriers generated by the exciting high-energy photons in the shell region are relaxed to the band-edge states of the core region and recombined to emit lower-energy photons. The activation energy of the carriers confined in the CdSe/CdS/ZnS core shell-shell QDs, as obtained from temperature-dependent PL spectra, was 200 meV. The quantum efficiency of the CdSe/CdS/ZnS core-shell-shell QDs at 300 K was estimated to be approximately 57%. PMID- 26832588 TI - Diffractive nanostructures for enhanced light-harvesting in organic photovoltaic devices. AB - We present in-coupling gratings for improving the performance of thin film organic solar cells. The impact of the grating on the absorption in the active layer is modeled and explained using a standard cell architecture. An increase in absorption of 14.8% is predicted and is shown to be independent from the active material. The structure is then applied on blade-coated devices and yields an efficiency improvement of 12%. The angular behavior of the structures is measured showing superior performance for two dimensional gratings. By simulating the current generation for different angles and illumination conditions, we predict a total yearly increase of the generated current of 12% using an optimized grating. The fabrication of these structures, moreover, is compatible with roll-to-roll production techniques, thus making them an optimal solution for printed photovoltaics. PMID- 26832589 TI - Spectral and total temperature-dependent emissivities of few-layer structures on a metallic substrate. AB - We investigate the thermal radiative emission of few-layer structures deposited on a metallic substrate and its dependence on temperature with the Fluctuational Electrodynamics approach. We highlight the impact of the variations of the optical properties of metallic layers on their temperature-dependent emissivity. Fabry-Perot spectral selection involving at most two transparent layers and one thin reflective layer leads to well-defined peaks and to the amplification of the substrate emission. For a single Fabry-Perot layer on a reflective substrate, an optimal thickness that maximizes the emissivity of the structure can be determined at each temperature. A thin lossy layer deposited on the previous structure can enhance interference phenomena, and the analysis of the participation of each layer to the emission shows that the thin layer is the main source of emission. Eventually, we investigate a system with two Fabry-Perot layers and a metallic thin layer, and we show that an optimal architecture can be found. The total hemispherical emissivity can be increased by one order of magnitude compared to the substrate emissivity. PMID- 26832590 TI - Directional sideward emission from luminescent plasmonic nanostructures. AB - Periodic arrays of metallic nanoparticles can be used to enhance the emission of light in certain directions. We fabricated hexagonal arrays of aluminium nanoparticles combined with thin layers of luminescent material and optimized period (275 nm) and thickness (1500 nm) to obtain sideward directional emission into glass for a wavelength band around 620 nm. The key physics is that the luminescent layer acts as a waveguide, from which light is emitted at preferential angles using diffractive effects. This phenomenon has applications in the field of solid-state lighting, where there is a desire for small, bright and directional sources. PMID- 26832591 TI - Spectrally-resolved measurement of concentrated light distributions for Fresnel lens concentrators. AB - A test method that measures spectrally resolved irradiance distribution for a concentrator photovoltaic (CPV) optical system is presented. In conjunction with electrical I-V curves, it is a means to visualize and characterize the effects of chromatic aberration and nonuniform flux profiles under controllable testing conditions. The indoor characterization test bench, METHOD (Measurement of Electrical, Thermal and Optical Devices), decouples the temperatures of the primary optical element (POE) and the cell allowing their respective effects on optical and electrical performance to be analysed. In varying the temperature of the POE, the effects on electrical efficiency, focal distance, spectral sensitivity, acceptance angle and multi-junction current matching profiles can be quantified. This work presents the calibration procedures to accurately image the spectral irradiance distribution of a CPV system and a study of system behavior over lens temperature. PMID- 26832592 TI - Enhanced light absorption in thin film silicon solar cells with Fourier-series based periodic nanostructures. AB - We proposed a Fourier-series based periodic nanostructure(FSPN) for light trapping in thin film silicon solar cells. By globally optimizing the Fourier coefficients across entire silicon absorption spectrum, we obtained a FSPN structure with short circuit current density greater than 24 mA/cm(2) for a 1MUm real silicon absorption layer. The spectral analysis shows at normal incidence the FSPN exhibits a collection effect of periodic gratings and performs over 84.6% better than random texture. The angular analysis shows that the FSPN outperforms grating and random textures within 70 degrees . PMID- 26832593 TI - Rear interface engineering of hybrid organic-silicon nanowire solar cells via blade coating. AB - In this work, we investigate blade-coated organic interlayers at the rear surface of hybrid organic-silicon photovoltaics based on two small molecules: Tris(8 hydroxyquinolinato) aluminium (Alq(3)) and 1,3-bis(2-(4-tert-butylphenyl)-1,3,4 oxadiazol-5-yl) benzene (OXD-7). In particular, soluble Alq(3) resulting in a uniform thin film with a root-mean-square roughness < 0.2nm is demonstrated for the first time. Both devices with the Alq(3) and OXD-7 interlayers show notable enhancement in the open-circuit voltage and fill-factor, leading to a net efficiency increase by over 2% from the reference, up to 11.8% and 12.5% respectively. The capacitance-voltage characteristics confirm the role of the small-molecule interlayers resembling a thin interfacial oxide layer for the Al Si Schottky barrier to enhance the built-in potential and facilitate charge transport. Moreover, the Alq(3) interlayer in optimized devices exhibits isolated phases with a large surface roughness, in contrast to the OXD-7 which forms a continuous uniform thin film. The distinct morphological differences between the two interlayers further suggest different enhancement mechanisms and hence offer versatile functionalities to the advent of hybrid organic-silicon photovoltaics. PMID- 26832594 TI - Preparation and characterization of two-dimensional metallic nanoparticle and void films derived from a colloidal template layer. AB - A novel and simple bottom-up fabrication method for the realization of metallic nanovoid and metallic film on nanoparticle (dome) array is presented and their optical performance assessed based on experimental and theoretical investigations. The structures are created by a simple, annealing induced replica formation of a template monolayer, which is composed of submicron particles deposited on top of a thin polymer film. Angle and wavelength dependent reflection measurements indicate the possibility to excite Bragg plasmons at the prepared structures. We found an excellent agreement between the measured and simulated reflection curves, but only when the simulated reflection was averaged over several possible azimuthal lattice orientations of the hexagonal unit cell with respect to the plane of incidence. PMID- 26832595 TI - Colloidal nanophotonics: the emerging technology platform. AB - Dating back to decades or even centuries ago, colloidal nanophotonics during the last ten years rapidly extends towards light emitting devices, lasers, sensors and photonic circuitry to manifest itself as an emerging technology platform rather than an entirely academic research field. PMID- 26832596 TI - Multiple-exposure colloidal lithography for enhancing light output of GaN-based light-emitting diodes by patterning Ni/Au electrodes. AB - Ni/Au electrodes with single, twined and triplet hole array patterns light emitting diodes have been fabricated by multiple-exposure colloidal lithography. It is found that 45.6%, 83.6% and 15.5% improvement in light output at 350 mA has been achieved by patterning Ni/Au electrodes with single, twined, triplet hole arrays. In addition, patterned Ni/Au LEDs possess much larger view angles than non-patterned ones due to scattering effects of light around the holes, especially for triplet hole array patterned Ni/Au LEDs. Our proposed method for fabricating multiple holes structure would be very promising to improve light output power of LEDs when using advanced electrodes. PMID- 26832597 TI - Quantum theory of electroabsorption in semiconductor nanocrystals. AB - We develop a simple quantum-mechanical theory of interband absorption by semiconductor nanocrystals exposed to a dc electric field. The theory is based on the model of noninteracting electrons and holes in an infinitely deep quantum well and describes all the major features of electroabsorption, including the Stark effect, the Franz-Keldysh effect, and the field-induced spectral broadening. It is applicable to nanocrystals of different shapes and dimensions (quantum dots, nanorods, and nanoplatelets), and will prove useful in modeling and design of electrooptical devices based on ensembles of semiconductor nanocrystals. PMID- 26832598 TI - Optical properties of ordered superstructures formed from cadmium and lead chalcogenide colloidal nanocrystals. AB - The optical properties of three-dimensional ordered superstructures formed on glass substrates by self-assembly of cadmium selenide or lead sulfide nanocrystals (NCs) are investigated and compared to the optical properties of the initial NC colloidal solutions. The formation of the superstructures is strongly correlated to the presence of oleic acid molecules on the surface of the NCs. It is found that the absorption band of the NCs in the superstructures is broadened and shifted to shorter wavelengths in comparison with the absorption band of the NCs in solution. The luminescence spectra of the NCs in the superstructures also differ from the spectra of the NCs in solution. The observed modification of optical properties of superstructures is a manifestation of interactions between the NCs and the chemical environment within the superstructures. PMID- 26832599 TI - Chiroptical activity in colloidal quantum dots coated with achiral ligands. AB - We studied the chiroptical properties of colloidal solution of CdSe and CdSe/ZnS quantum dots (QDs) with a cubic lattice structure which were initially prepared without use of any chiral molecules and coated with achiral ligands. We demonstrate circular dichroism (CD) activity around first and second excitonic transition of these CdSe based nanocrystals. We consider that this chiroptical activity is caused by imbalance in racemic mixtures of QDs between the left and right handed nanoparticles, which appears as a result of the formation of various defects or incorporation of impurities into crystallographic structure during their synthesis. We demonstrate that optical activity of colloidal solution of CdSe QDs with achiral ligands weakly depends on the QDs size and number of ZnS monolayers, but does not depend on the nature of achiral ligands or polarity of the solution. PMID- 26832600 TI - Excitonic improvement of colloidal nanocrystals in salt powder matrix for quality lighting and color enrichment. AB - Here we report excitonic improvement in color-converting colloidal nanocrystal powders enabled by co-integrating nonpolar green- and red-emitting nanocrystal energy transfer pairs into a single LiCl salt matrix. This leads to nonradiative energy transfer (NRET) between the co-integrated nanocrystals in the host matrix. Here we systematically studied the resulting NRET process by varying donor and acceptor concentrations in the powders. We observed that NRET is a strong function of both of the nanocrystal concentrations and that NRET efficiency increases with increasing acceptor concentration. Nevertheless, with increasing donor concentration in the powders, NRET efficiency was found to first increase (up to a maximum level of 53.9%) but then to decrease. As a device demonstrator, we employed these NRET-improved nanocrystal powders as color-converters on blue light-emitting diodes (LEDs), with the resulting hybrid LED exhibiting a luminous efficiency >70 lm/W(elect). The proposed excitonic nanocrystal powders potentially hold great promise for quality lighting and color enrichment applications. PMID- 26832601 TI - Dopamine sensing and measurement using threshold and spectral measurements in random lasers. AB - We developed a novel dopamine sensing and measurement technique based on aggregation of gold nanoparticles in random lasers. Dopamine combined with copper ions triggers the aggregation of gold nanoparticles and thus affects the performance of random lasers. Dopamine sensing can be achieved using four parameters which are sensitive to the presence of dopamine, that is emission peak shift, emission linewidth, signal-to-noise ratio (peak emission intensity / noise) and random lasing threshold. The dopamine is most sensitively detected by a change in the emission linewidth with a limit of detection of 1 * 10(-7) M, as well as by an increase in the lasing threshold. The dopamine concentration from 1 * 10(-7) M to 1 * 10(-2) M can be determined by calibrating with the laser threshold. PMID- 26832602 TI - Colorful solar selective absorber integrated with different colored units. AB - Solar selective absorbers are the core part for solar thermal technologies such as solar water heaters, concentrated solar power, solar thermoelectric generators and solar thermophotovoltaics. Colorful solar selective absorber can provide new freedom and flexibility beyond energy performance, which will lead to wider utilization of solar technologies. In this work, we present a monolithic integration of colored solar absorber array with different colors on a single substrate based on a multilayered structure of Cu/TiN(x)O(y)/TiO(2)/Si(3)N(4)/SiO(2). A colored solar absorber array with 16 color units is demonstrated experimentally by using combinatorial deposition technique via changing the thickness of SiO(2) layer. The solar absorptivity and thermal emissivity of all the color units is higher than 92% and lower than 5.5%, respectively. The colored solar selective absorber array can have colorful appearance and designable patterns while keeping high energy performance at the same time. It is a new candidate for a number of solar applications, especially for architecture integration and military camouflage. PMID- 26832603 TI - Graphene Oxide Quantum Dots Covalently Functionalized PVDF Membrane with Significantly-Enhanced Bactericidal and Antibiofouling Performances. AB - Covalent bonding of graphene oxide quantum dots (GOQDs) onto amino modified polyvinylidene fluoride (PVDF) membrane has generated a new type of nano-carbon functionalized membrane with significantly enhanced antibacterial and antibiofouling properties. A continuous filtration test using E. coli containing feedwater shows that the relative flux drop over GOQDs modified PVDF is 23%, which is significantly lower than those over pristine PVDF (86%) and GO-sheet modified PVDF (62%) after 10 h of filtration. The presence of GOQD coating layer effectively inactivates E. coli and S. aureus cells, and prevents the biofilm formation on the membrane surface, producing excellent antimicrobial activity and potentially antibiofouling capability, more superior than those of previously reported two-dimensional GO sheets and one-dimensional CNTs modified membranes. The distinctive antimicrobial and antibiofouling performances could be attributed to the unique structure and uniform dispersion of GOQDs, enabling the exposure of a larger fraction of active edges and facilitating the formation of oxidation stress. Furthermore, GOQDs modified membrane possesses satisfying long-term stability and durability due to the strong covalent interaction between PVDF and GOQDs. This study opens up a new synthetic avenue in the fabrication of efficient surface-functionalized polymer membranes for potential waste water treatment and biomolecules separation. PMID- 26832604 TI - Stratification of risk to the surgical team in removal of small arms ammunition implanted in the craniofacial region: case report. AB - In cases of penetrating injury with implantation of small arms ammunition, it can often be difficult to tell the difference between simple ballistics and ballistics associated with unexploded ordnances (UXOs). In the operative environment, where highly flammable substances are often close to the surgical site, detonation of UXOs could have catastrophic consequences for both the patient and surgical team. There is a paucity of information in the literature regarding how to evaluate whether an implanted munition contains explosive material. This report describes a patient who presented during Operation Enduring Freedom with an implanted munition suspicious for a UXO and the subsequent workup organized by Explosive Ordnance Disposal (EOD) Company prior to surgical removal. Clinical risk factors for UXOs include assassination attempts and/or wartime settings. Specific radiological features suggestive of a UXO include projectile size greater than 7.62-mm caliber, alterations in density of the tip, as well as radiological evidence of a hollowed-out core. If an implanted UXO is suspected, risks to the surgical and anesthesia teams can be minimized by notifying the nearest military installation with EOD capabilities and following clinical practice guidelines set forth by the Joint Theater Trauma System. PMID- 26832605 TI - Siderophore inspired tetra- and octadentate antenna ligands for luminescent Eu(III) and Tb(III) complexes. AB - Following the success of the siderophore-inspired 1,2-hydroxypyridonate (HOPO) and 2-hydroxisophthalamide (IAM) chromophores in Eu(III) and Tb(III) luminescence, we designed three new ligands bearing both chromophores. Syntheses of the octadentate ligands 3,4,3-LI-IAM-1,2-HOPO and 3,4,3-LI-1,2-HOPO-IAM, where the chromophores are attached to different positions in the (LI=linear) spermine backbone, are reported in addition to a tetradentate ligand based on 1,5 diaminopentane. The Gd(III) complexes were prepared and revealed localized triplet states typical for the IAM and HOPO chromophores. Photophysical characterization of the Eu(III) and Tb(III) complexes revealed that the chromophores need to reside at a primary amine of the spermine backbone to be efficient in lanthanide excitation. These systems help us to understand the antenna effect in siderophore inspired chromophores and could be potential targets for sensing and biological imaging applications. PMID- 26832607 TI - Cell identity: a matter of lineage and neighbours. PMID- 26832606 TI - Callous traits in children with and without conduct problems predict reduced connectivity when viewing harm to others. AB - The presence of elevated callous unemotional (CU) traits seems to designate a distinct group of children and adolescents with serious conduct problems. However, the extent to which CU traits impact the aversive reaction to harm is still a contentious issue. Here, we examined the effective connectivity seeded in the anterior insula and anterior cingulate cortex in a large number of children (N = 123, age 9-11, 60 females) with various levels of conduct disorder (CD) symptoms in response to visual stimuli depicting other people being physically injured. Perceiving others being harmed was associated with increased hemodynamic activity in the left amygdala and right temporoparietal junction (rTPJ). Children with higher callous traits showed less functional connectivity seeded in anterior cingulate with left amygdala and anterior insula. Conversely, CD symptoms were positively related to connectivity of insula with rTPJ. Overall, these results suggest that callousness is marked by the disruption of widespread cortical networks responsible for detecting and appropriately responding to important environmental cues, such as the distress of others. PMID- 26832608 TI - Evaluation of a Novel Intervention to Reduce Unnecessary Urine Cultures in Intensive Care Units at a Tertiary Care Hospital in Maryland, 2011-2014. AB - We assessed the impact of a reflex urine culture protocol, an intervention aimed to reduce unnecessary urine culturing, in intensive care units at a tertiary care hospital. Significant decreases in urine culturing rates and reported rates of catheter-associated urinary tract infection followed implementation of the protocol. PMID- 26832609 TI - A minimally invasive technique to assess several life-history characteristics of the endangered great hammerhead shark Sphyrna mokarran. AB - A dorsal-fin photo-identification technique paired with a non-invasive parallel laser photogrammetry technique was used to non-invasively identify individual Sphyrna mokarran over time. Based on the data collected over a duration of 59 days, 16 different S. mokarran (mean +/- S.D. pre-caudal length: 220.82 +/- 13.66 cm; mean +/- S.D. cephalofoil width: 71.38 +/- 7.94 cm) were identified using dorsal-fin photo-identification, with a mean +/- S.D. shark re-sighting frequency of 4.05 +/- 3.06 at-sea days. The results illustrate a high S. mokarran sighting rate and therefore, the utilization of parallel laser photogrammetry and dorsal fin photo-identification may be a plausible multi-year approach to aid in non invasively determining the growth rate and inter-annual site fidelity of these animals. PMID- 26832610 TI - [Preface]. PMID- 26832611 TI - [Evaluation of Motion Sickness Induced by 3D Video Clips]. AB - The use of stereoscopic images has been spreading rapidly. Nowadays, stereoscopic movies are nothing new to people. Stereoscopic systems date back to 280 A.D. when Euclid first recognized the concept of depth perception by humans. Despite the increase in the production of three-dimensional (3D) display products and many studies on stereoscopic vision, the effect of stereoscopic vision on the human body has been insufficiently understood. However, symptoms such as eye fatigue and 3D sickness have been the concerns when viewing 3D films for a prolonged period of time; therefore, it is important to consider the safety of viewing virtual 3D contents as a contribution to society. It is generally explained to the public that accommodation and convergence are mismatched during stereoscopic vision and that this is the main reason for the visual fatigue and visually induced motion sickness (VIMS) during 3D viewing. We have devised a method to simultaneously measure lens accommodation and convergence. We used this simultaneous measurement device to characterize 3D vision. Fixation distance was compared between accommodation and convergence during the viewing of 3D films with repeated measurements. Time courses of these fixation distances and their distributions were compared in subjects who viewed 2D and 3D video clips. The results indicated that after 90 s of continuously viewing 3D images, the accommodative power does not correspond to the distance of convergence. In this paper, remarks on methods to measure the severity of motion sickness induced by viewing 3D films are also given. From the epidemiological viewpoint, it is useful to obtain novel knowledge for reduction and/or prevention of VIMS. We should accumulate empirical data on motion sickness, which may contribute to the development of relevant fields in science and technology. PMID- 26832612 TI - [Limits of Cognition with Visual Parallax of Stereoscopic Images]. AB - OBJECTIVES: Recent advances in three-dimensional (3D) display technology have contributed significantly to society, particularly in the increasing use of stereoscopic characters. For example, 3D text information is utilized in digital signage. However, research on 3D characters is limited and discussion on the safety and comfort of 3D technology is lacking. According to the 3D Consortium Safety Guidelines in Japan, a comfortable visual parallax with 3D images is less than +/-1.0 degrees . However, 3D text must be shown in front of its associated content in order for it to be displayed simultaneously with that content. METHODS: We carried out an experiments to verify the permissive limits of cognition in subjects regarding the parallax of 3D images. In the experiment, 94 subjects aged 18 to 81 viewed a 3D flat Maltess cross image having no depth and projected outward from a screen at a large parallax of 1.0 degrees to 6.0 degrees . RESULTS: Eighty-six percent of the subjects recognized the 3D flat image even when it protruded at a 2.0 degrees parallax. These subjects viewed the image comfortably and without visual problems. CONCLUSIONS: This study concludes that people can cognitively recognize a 3D telop at a 2.0 degrees parallax without feeling fatigued. PMID- 26832613 TI - [Temporal Analysis of Body Sway during Reciprocator Motion Movie Viewing]. AB - OBJECTIVES: We aimed to investigate the effect of stereoscopic viewing and the degree of awareness of motion sickness on posture by measuring body sway during motion movie viewing. METHODS: Nineteen students (12 men and 7 women; age range, 21-24 years) participated in this study. The movie, which showed several balls randomly positioned, was projected on a white wall 2 m in front of the subjects through a two-dimensional (2-D)/three-dimensional (3-D) convertible projector. To measure body sway during movie viewing, the subjects stood statically erect on a Wii balance board, with the toe opening at 18 degrees. The study protocol was as follows: The subjects watched (1) a nonmoving movie for 1 minute as the pretest and then (2) a round-trip sinusoidally moving-in-depth-direction movie for 3 minutes. (3) The initial static movie was shown again for 1 minute. Steps (2) and (3) were treated as one trial, after which two trials (2-D and 3-D movies) were performed in a random sequence. RESULTS: In this study, we found that posture changed according to the motion in the movie and that the longer the viewing time, the higher the synchronization accuracy. These tendencies depended on the level of awareness of motion sickness or the 3-D movie viewed. CONCLUSIONS: The mechanism of postural change in movie viewing was not vection but self-defense to resolve sensory conflict between visual information (spatial swing) and equilibrium sense (motionlessness). PMID- 26832614 TI - [Effect of Viewing a Long Stereoscopic Film on Equilibrium Function and Autonomic Nervous System]. AB - OBJECTIVES: Owing to the recent rapid advancements in image processing and three dimensional (3-D) technologies, stereoscopic images can now be viewed on television as well as in theaters and on gaming consoles among others. However, with these advancements, there have also been reports on motion sickness and asthenopia induced by viewing stereoscopic films. Human equilibrium function deteriorates when viewing stereoscopic films, which may lead to motion sickness; however, the exact cause of such motion sickness remains unknown. Therefore, as part of hygiene research that contributes to society, it is important to consider the safety of viewing virtual 3D contents. METHODS: In this study, we investigated the effects of viewing 2-D/3-D video clips on the human body by stabilometry, electrogastrography (EGG), and subjective assessments. Seven subjects aged 22 to 24 viewed 2-D/3-D video clips for 60 min. RESULTS: A comparison of time series data obtained at rest shows a significant change in the EGG patterns 20 min after the start of viewing the video clips. Furthermore, sway values while viewing the 3-D video clips were considerably higher than those while viewing the 2-D video clips 60 min after the start of viewing. CONCLUSIONS: These findings show that the autonomic nervous system is affected first by long term viewing of stereoscopic films, and the equilibrium function deteriorates gradually over the course of the exposure. PMID- 26832615 TI - [Environmental Effect In Utero for Adult Disease]. AB - Worldwide, lifestyle-related diseases such as type 2 diabetes and cardiovascular diseases are presently the leading causes of death and disability, and their incidences tend to increase. A lifestyle-related disease has been considered mainly to be induced by specific disease susceptibility genes and lifestyle after birth. However, the steep increase in the incidences of lifestyle-related diseases is difficult to be explained only by specific genes. Presently, a new theory has been proposed. Epidemiological and animal studies have disclosed the intimate links between malnutrition in the developmental stage and lifestyle related chronic diseases. Such studies provide the foundation and framework for a new life science, that is, the theory of developmental origins of health and diseases (DOHaD). Although much research has been carried out to elucidate the putative concepts and mechanisms that relate specific exposures in early life to the risk of chronic diseases, a complete picture still remains obscure. Historically, the world has experienced severe famines, for example, the Dutch Winter Famine, the Chinese Great Leap Forward Famine, the Leningrad Siege and the Biafran Famine. These famines showed that malnutrition in utero poses higher risks of lifestyle-related diseases. The main research point has been focused on periconceptional and perinatal undernutrition and specific nutrient deficiencies. However, presently, the number of people who are overweight and obese has been increasing. Therefore, perinatal overnutrition and specific nutrient excesses should also be examined. In addition, psychological stress, environmental chemicals and artificial reproductive techniques are other important research fields in DOHaD. PMID- 26832616 TI - [Developmental Origins of Health and Disease (DOHaD) and Epidemiology]. AB - Japan has the highest proportion of low-birth-weight infants among OECD countries for over 20 years. In 2011, the proportion of low-birth-weight infants in Japan was 9.6%, whereas the mean proportion in OECD countries was only 6.8%. In particular, young Japanese women's strong desire to be thin has been pointed out as the underlying cause. Indeed, the frequencies of unhealthy thinness among third-year female junior and senior high school Japanese students have been increasing since the start of "Healthy Parents and Children 21", and both groups have reached about 20%. The hypothesis of the fetal origins of adult disease (Barker's theory) was proposed by Professor David J. Barker of Southampton University, who had conducted descriptive epidemiological studies in England and Wales and birth cohort studies in Hertfordshire, for example. In early 21st century, it became the wider theory known as the "Developmental Origins of Health and Disease (DOHaD)", which was composed of developmental plasticity and the mismatch concept. Birth cohort studies are believed to be suitable for epidemiological studies to demonstrate the DOHaD theory. These studies and their collaborations are very popular in European countries, whereas such collaborations lagged behind in Japan. Recently, a new paradigm, "preemptive medicine", has been proposed in Japan. The importance of interdisciplinary studies focusing on fetal and childhood periods was also recommended as a political strategy. We just expect the realization of nationwide large-scale interdisciplinary research projects based on DOHaD and preemptive medicine and the establishment of a central research institute of these studies. PMID- 26832617 TI - [Current State of Studies on Job-related Stress among Psychiatric Social Workers and Insights into Future Research]. AB - We studied the characteristics of psychiatric social workers (PSWs) and present research on job-related stress among them; we also provide insights into the future of such research. In recent years, studies on job-related stress among PSWs have been gaining interest. In particular, stress associated with the repeated revisions of related laws has increased. Subsequently, it was found that occupational stress in PSWs differs qualitatively and quantitatively depending on educational history, years of experience, and service department. However, no scale captures the specific characteristics of job-related stress among PSWs. Moreover, the development of a mental health care program for PSWs seems difficult. To develop a mental health care program that caters specifically to this group, future research should focus on developing a scale that determines the specific characteristics of job-related stress among PSWs, which should be evaluated on the basis of each PSW's educational history, years of experience, and service department. PMID- 26832618 TI - [Fundamental Properties of Aldehyde Dehydrogenase 2 (ALDH2) and the Importance of the ALDH2 Polymorphism]. AB - Human aldehyde dehydrogenase 2 (ALDH2) is a 56 kDa mitochondrial protein that forms homodimers through hydrogen bonding interactions between the Glu487 and Arg475 residues of two ALDH2 proteins. Two ALDH2 homodimers can interact to form an ALDH2 tetramer. ALDH2 is widely distributed throughout the organs of the body. In addition to its dehydrogenase activity, ALDH2 also exhibits esterase and reductase activities, with the main substrates for these three activities being aldehydes, 4-nitrophenyl acetate and nitroglycerin, respectively. ALDH2 can be readily inhibited by a wide variety of endogenous and exogenous chemicals, but the induction or activation of this enzyme remains unlikely. The polymorphism of ALDH2 to the corresponding ALDH2*2 variant results in a severe deficiency in ALDH2 activity, and this particular polymorphism is prevalent among people of Mongoloid descent. It seems reasonable to expect that people with the ALDH2*2 variant would be more vulnerable to stress and diseases because ALDH2 defends the human body against toxic aldehydes. However, it has been suggested that people with the ALDH2*2 variant are protected by alternative stress-defending systems. The ALDH2*2 variant has been reported to be associated with many different kinds of diseases, although the mechanisms underlying these associations have not yet been elucidated. ALDH2 polymorphism has a significant impact on human health; further studies are therefore required to determine the practical implications of this polymorphism in the fields of preventive and clinical medicine. PMID- 26832619 TI - [Relationship between Explanation from Guardians and Preventive Behaviors against Uterine Cervical Cancer at the Time of Inoculation of HPV Vaccine]. AB - OBJECTIVES: The purpose of this study is to clarify whether the explanation received from the guardian at the time of inoculation of a HPV vaccine is related to preventive behaviors against uterine cervical cancer among junior high school girls. The preventive behaviors were set as "wishing to receive the HPV vaccination" and "considering on sexual behaviors (dating, kissing, sexual relations)." METHODS: An anonymous self-administered questionnaire survey was performed on 206 second-year junior high school girls who were candidates for the inoculation of the HPV vaccine in the previous year. We considered that a subject received an explanation on HPV vaccination if she received explanations on this topic, such as "an HPV vaccine prevents uterine cancer." We considered that a subject received an explanation on pubertal events if she received explanations on this topic, such as "the importance of a life." Including these two variables among the independent variables, multiple logistic regression analysis was performed. RESULTS: The knowledge on uterine cancer was promoted when the subjects received explanations about the HPV vaccination. Many subjects received explanations on pubertal events by receiving explanations on HPV vaccination. The guardian's explanation about HPV vaccination was one of the factors related to "wishing to receive the HPV vaccination" and "considering on sexual behaviors." CONCLUSION: It is important for guardians to explain to their children about HPV vaccination without hesitation at the time of the vaccination. PMID- 26832620 TI - [Measurement of Nicotine, Tobacco-Specific Nitrosamines, and Additives in the Filler and Gas from Japanese Brand Snuff]. AB - OBJECTIVE: The World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) reported that understanding the use and impact of smokeless tobacco (SLT) products is complicated by product diversity. Many different SLT products with different characteristics are used worldwide. ZERO STYLE STIX(TM) (sold by Japan Tobacco Inc.) is a brand of snuff, a type of smokeless tobacco. Our objective was to determine the constituents of the gas from SLT and analyze the ingredients in tobacco fillers. METHODS: ZERO STYLE STIX smokeless tobacco was released in the Japanese market in 2010. Nicotine, menthol, and tobacco specific nitrosamines in the smokeless tobacco fillers were determined by gas chromatography-mass spectrometry (GC/MS) and liquid chromatography-tandem mass spectrometry (LC/MS/MS). The gaseous compounds were collected by a smoking machine using two smoking protocols, i.e., the ISO and Health Canada Intense methods. Nicotine and menthol in the gas were determined by GC/MS. RESULTS: Nicotine, menthol, and the total tobacco-specific nitrosamines were detected in the tobacco fillers. The level of menthol in the snuff was more than ten times that of nicotine. The determined levels of the two components of the gas from the snuff were higher when using the Health Canada Intense protocol than when using the ISO protocol. In addition, flavors other than menthol were emitted from the smokeless tobacco. CONCLUSION: The new type of snuff introduced in the Japanese market in 2010 contained added flavors, and was attractive smokeless tobacco. Flavors in tobacco products need to regulate on the basis of FCTC 9 and 10 in JAPAN. PMID- 26832621 TI - [Determination of Polycyclic Aromatic Hydrocarbons and Mutagenicity of Mainstream Smoke and Heavy Metals in Tobacco Filler of Cigarettes of a Brand in Japan and Cigarettes of the Same Brand Imported Privately from Other Asian Countries]. AB - OBJECTIVE: Some Japanese smokers imported Japanese cigarette brands from other Asian countries for personal use because of the increase in tobacco tax in 2010, which meant that privately importing the cigarettes was cheaper than purchasing them in Japan. We assumed that the health hazards of locally made cigarettes were different from those of privately imported cigarettes, despite the brands being the same. In this study, we carried out a comparative toxicological analysis of domestic and privately imported cigarettes. METHODS: Privately imported cigarettes of five brands and domestic cigarettes of the brand named "MILD SEVEN ORIGINAL" were selected for the study. The level of polycyclic aromatic hydrocarbons (PAHs) in mainstream smoke was determined by high-performance liquid chromatography using fluorescence detection. The mutagenicity of mainstream smoke was assessed using the Salmonella typhimurium strains TA100, TA98, and YG1024 with the metabolic activation system (S9mix) by preincubation assay. The levels of heavy metals in cigarette fillers were determined by inductively coupled plasma-mass spectrometry. RESULTS: The level of PAH in the mainstream smoke from the privately imported cigarettes was higher than that in the smoke from the domestic cigarettes. However, the mutagenic activity of the mainstream smoke from the privately imported cigarettes was equivalent to that from the domestic cigarettes. The levels of nickel and cadmium in the fillers of the privately imported cigarettes were higher than those in the domestic cigarettes. CONCLUSION: The levels of constituents in the fillers and mainstream smoke from the privately imported cigarettes were higher than those in the fillers and mainstream smoke from the domestic cigarettes. The majority of Japanese smokers are unaware of these findings. The guidelines regulating tobacco products recommend that articles 9 and 10 of the World Health Organization (WHO) Framework Convention on Tobacco Control should be fully implemented in Japan. PMID- 26832622 TI - [Outline of the Japan Environment and Children's Study and the Framework of Genome Analysis]. AB - The goal of the Japan Environment and Children's Study (JECS) is to improve the health and welfare of children and to contribute to better risk management of chemical substances in the environment. The study will examine hypotheses related to reproduction, congenital anomalies, neuropsychiatric development, immunity, metabolism and endocrine system. The hypotheses will be tested for indicative outcomes in combination with exposure to chemicals, as well as confounders and modulators, such as chemical, physical, genetic, social and lifestyle-related factors. A total of 100,000 pregnant women associated with the selected study locations were recruited during the first three years starting January 2011. Their children will be followed up until the age of 13 years. The main study (nationwide survey) will include all participants recruited in all regional centres. Substudies will be conducted on randomly selected individuals from among all the participants. In the main and substudies, blood, urine, hair and breast milk samples will be collected from mothers. Blood, hair, and urine samples as well as umbilical cord blood at delivery will be collected from the children. Blood samples will also be collected from fathers. Each specimen will be analysed for specific chemical substances. In addition, genetic background will be evaluated. The collected blood samples for genetic assessments will be stored at the national centre. The detailed assessment procedures will be reviewed for approval by IRBs. PMID- 26832623 TI - [Application of Metabolomics to Multiple Chemical Sensitivity Research]. AB - Multiple chemical sensitivity (MCS) is an acquired chronic disorder characterized by nonspecific symptoms in multiple organ systems associated with exposure to low level chemicals. Diagnosis of MCS can be difficult because of the inability to assess the causal relationship between exposure and symptoms. No standardized objective measures for the identification of MCS and no precise definition of this disorder have been established. Recent technological advances in mass spectrometry have significantly improved our capacity to obtain more data from each biological sample. Metabolomics comprises the methods and techniques that are used to determine the small-level molecules in biofluids and tissues. The metabolomic profile-the metabolome-has multiple applications in many biological sciences, including the development of new diagnostic tools for medicine. We performed metabolomics to detect the difference between 9 patients with MCS and 9 controls. We identified 183 substances whose levels were beyond the normal detection limit. The most prominent differences included significant increases in the levels of both hexanoic acid and pelargonic acid, and also a significant decrease in the level of acetylcarnitine in patients with MCS. In conclusion, using metabolomics analysis, we uncovered a hitherto unrecognized alteration in the levels of metabolites in MCS. These changes may have important biological implications and may have a significant potential for use as biomarkers. PMID- 26832624 TI - [Food Sanitation Act and Minamata Disease]. AB - Immediately after the official recognition of Minamata disease (1956.5.l) a study group at Kumamoto University suggested that Minamata disease was caused by food poisoning. The next year, this suggestion was accepted by the Ministry of Health and Welfare (MHW). Prior to the decision to apply the Food Sanitation Act (FSA), the local government asked MHW for the application of FSA. Soon after, the chief of the Public Health Bureau replied to the local government that the application of FSA to the Minamata area was impossible. Epidemiological investigations of residents and polluted areas, therefore, were not carried out. Data essential for the screening for exposed residents were unavailable. The criteria for the screening were presented. The Environmental Agency (EA) presented the criteria in the form of notice in 1971, which were revised in 1977. Notwithstanding the clear difference between the original and revised criteria, EA insisted that these two sets of criteria were quite similar. This insistence by EA and the absence of epidemiological data on residents and polluted area resulted in the present confusion about Minamata disease. The application of FSA was stopped by bureaucrats who had no interest in the environmental problems and by several scientists patronized by stakeholders (Chisso, Japanese Association of Chemical Industries, MHW and EA). Stakeholders suppressed science. PMID- 26832626 TI - Aqueous oxidation reaction enabled layer-by-layer corrosion of semiconductor nanoplates into single-crystalline 2D nanocrystals with single layer accuracy and ionic surface capping. AB - A controllable aqueous oxidation reaction enabled layer-by-layer corrosion has been proposed to prepare high-quality two-dimensional (2D) semiconductor nanocrystals with single layer accuracy and well-retained hexagonal shapes. The appropriate oxidizing agent, such as H2O2, Fe(NO3)3, and HNO3, could not only corrode the layered-crystalline-structured Bi2Te3 nanoplates layer-by-layer to be a single quintuple layer, but also replace the organic barriers to be ionic ligands on the surface synergistically. AFM analysis was used to confirm the layer-by-layer exfoliation from the side to the center. Together with precise XRD, LRTEM and HRTEM characterizations, the controllable oxidation reaction enabled aqueous layer-by-layer corrosion mechanism has been studied. PMID- 26832627 TI - Macular choroidal thickness in non-arteritic ischemic optic neuropathy. AB - OBJECTIVE: To analyse macular choroidal thickness (MCT) in non-arteritic ischaemic optic neuropathy (NAION). MATERIALS AND METHODS: An analysis was made on 22 patients diagnosed with NAION (22 eyes) and 42 healthy controls (42 eyes) using enhanced-depth imaging of spectral-domain optical coherence tomography. A horizontal raster scan centred on the fovea was obtained per eye 3 months after the onset of NAION. Three measurements of MCT were obtained from the posterior edge of the retinal pigment epithelium to the choroid-sclera junction at 500MUm intervals. Statistical analysis was used to compare the mean MCT and to correlate MCT with other ocular and systemic parameters. RESULTS: Except for refractive error (P=.01), there were no statistically significant differences between both groups in axial length (P=.53), age (P=.88) and other epidemiological and ocular parameters. Mean MCT in NAION eyes and control group was 236.21+/-63.29MUm and 269.13+/-52.28, respectively. Mean MCT was significantly thinner in NAION eyes than in healthy eyes (P=.03). Thinner MCT, adjusted for refractive error, was associated with the diagnosis of NAION (P=.04). CONCLUSIONS: Eyes affected by NAION showed significantly thinner MCT compared with healthy control eyes after adjusting for refractive error. PMID- 26832628 TI - Juxtapapillary neovascular membrane secondary to idiopathic intracranial hypertension treated with intravitreal bevacizumab: A case report. AB - CASE REPORT: A 48 year-old woman with visual acuity loss in left eye (0.3). Funduscopic examination showed papillary oedema and neovascular membrane in the left eye. All neurological tests were normal, except the lumbar puncture with opening pressure of 35cmH2O, being diagnosed with idiopathic intracranial hypertension (IIH). After four doses of bevacizumab, the visual acuity of the left eye has not improved and is counting fingers. DISCUSSION: Pathogenesis of the juxtapapillary neovascular membrane associated with IIH is not well known. An effect was observed after the anti-VEGF treatment. In our case, there was no improvement after four doses of intravitreal bevacizumab. PMID- 26832629 TI - Streptozotocin-induced diabetes, and the optic nerve blood barrier. AB - OBJECTIVE: To study the features of the endoneurial micro-vessels of the optic nerve in streptozotocin-induced diabetic animals. METHODS: Optic nerves from control and streptozotocin-induced diabetic animals were studied by light and transmission electron microscopy. Patency was determined by indirect immunofluorescence albumin detection. The expression of major histocompatibility complex class II molecules was performed by direct immunofluorescence. The endoneurial vessels were counted, and the endothelial cell, the basement membrane, and the surface of the transverse section of the nerve were measured. RESULTS: Vessels of diabetic rats showed vessel wall thickening, preservation of pericytes, an increase in endothelial cell transcytosis, and an increased number of perivascular macrophage cells. It may be concluded that the effects of hyperglycaemia on the inner vessels of the optic nerve are more similar to the cerebral diabetic vessels than to the retinal vessels in diabetic animals. PMID- 26832630 TI - Diagnosis of temporomandibular joint disorders: indication of imaging exams. AB - INTRODUCTION: Knowledge of the different imaging tests and their appropriate indications is crucial to establish the diagnosis of temporomandibular disorders, especially in patients with overlapping signs and symptoms. OBJECTIVE: To present and assess the main diagnostic imaging tests for temporomandibular disorders and rationally discuss their indication criteria, advantages, and disadvantages. METHODS: Literature review in the Web of Knowledge, PubMed and SciELO databases, as well as manual search for relevant publications in reference lists of the selected articles. RESULTS: Computed tomography and magnetic resonance imaging were considered the gold standard assessments for the temporomandibular joint to evaluate hard and soft tissues, respectively. Each diagnostic method exhibited distinct sensitivity and specificity for the different subtypes of joint dysfunction. CONCLUSION: Selecting an evaluation examination based on its accuracy, safety, and clinical relevance is a rational decision that can help lead to an accurate diagnosis and an optimum treatment plan. PMID- 26832631 TI - Malignant tumors of the temporal bone - our experience. AB - INTRODUCTION: Malignant tumors of the temporal bone are rare, with an estimated incidence of about 0.8-1.0 per 1,000,000 inhabitants per year. The vast majority of these tumors are squamous cell carcinomas and their treatment is eminently surgical. OBJECTIVE: This study is an attempt at systematizing the forms of clinical presentation, the therapeutic possibilities, and oncological outcomes of patients with malignant tumors of the temporal bone in a tertiary hospital in Portugal. METHODS: The authors present a retrospective study of temporal bone tumors treated and followed during otorhinolaryngology consultations between 2004 and 2014. A review of the literature is also included. RESULTS: Of the 18 patients included in the study, 16 had a primary tumor of the temporal bone, in most cases with squamous cell carcinoma histology. Of these, 13 patients were treated with curative intent that always included the surgical approach. Disease persistence was observed in one patient and local recurrence in five patients, on average 36.8 months after the initial treatment. CONCLUSIONS: The anatomical complexity of the temporal bone and the close associations with vital structures make it difficult to perform tumor resection with margins of safety and thus, tumor relapses are almost always local. A high level of suspicion is crucial for early diagnosis, and stringent and prolonged follow-up after treatment is essential for diagnosis and timely treatment of recurrances. PMID- 26832632 TI - Vestibular rehabilitation with visual stimuli in peripheral vestibular disorders. AB - INTRODUCTION: Visual stimuli can induce vestibular adaptation and recovery of body balance. OBJECTIVE: To verify the effect of visual stimuli by digital images on vestibular and body balance rehabilitation of peripheral vestibular disorders. METHODS: Clinical, randomized, prospective study. Forty patients aged between 23 and 63 years with chronic peripheral vestibular disorders underwent 12 sessions of rehabilitation with visual stimuli using digital video disk (DVD) (experimental group) or Cawthorne-Cooksey exercises (control group). The Dizziness Handicap Inventory (DHI), dizziness analog scale, and the sensitized Romberg static balance and one-leg stance tests were applied before and after the intervention. RESULTS: Before and after the intervention, there was no difference between the experimental and control groups (p>0.005) regarding the findings of DHI, dizziness analog scale, and static balance tests. After the intervention, the experimental and control groups showed lower values (p<0.05) in the DHI and the dizziness analog scale, and higher values (p<0.05) in the static balance tests in some of the assessed conditions. CONCLUSION: The inclusion of visual stimuli by digital images on vestibular and body balance rehabilitation is effective in reducing dizziness and improving quality of life and postural control in individuals with peripheral vestibular disorders. PMID- 26832633 TI - The influence of growth factors on skin wound healing in rats. AB - INTRODUCTION: Healing is a process that restores the physical integrity of body structures. It is a dynamic, complex, multicellular process that involves the extracellular matrix, cytokines, blood cells, and growth factors. Growth factors are proteins that activate and stimulate cell proliferation through the activation of angiogenesis, mitogenesis, and gene transcription, accelerating the healing process. OBJECTIVE: To assess the influence of growth factors on the healing process of wounds made on the backs of female rats compared to the control wound, through macro and microscopy. METHODS: This study used 45 female Wistar rats, in which three wounds were made on the back. The first was the control wound, the second received epithelial growth factor injection, and the third received a combination of factors. Macroscopic and microscopic assessments were performed on the third, seventh, and 15th days of the experiment. For microscopic analysis, hematoxylin-eosin staining was utilized to assess the inflammatory process; vimentin, for assessment of blood vessels and fibroblasts, and Sirius Red for collagen assessment. RESULTS: In the macroscopic assessment, the use of growth factors resulted in faster healing and decrease of granulation tissue on days seven and 15; (80.31% reduction in the control wound vs. 83.24% in the epithelial wound vs. 100% in the mixed wound). Utilizing microscopy, at the three stages of the experiment, there were no significant differences between the three wounds; however, when comparing the day of euthanization for each type of wound, there was a favorable outcome for epithelial and mixed wounds (between the third vs. 15th day, p<0.001, and in the comparison of the seventh vs. 15th day; p=0.002 and p=0.001 for epithelial and mixed wounds, respectively) with a higher number of fibroblasts, angiogenesis, and collagen type I. CONCLUSION: The use of growth factors accelerates healing, stimulates greater angiogenic activity, and accelerates fibroplasia and collagen maturation. PMID- 26832634 TI - Incidence and endoscopic characteristics of acute laryngeal lesions in children undergoing endotracheal intubation. AB - INTRODUCTION: Acute laryngeal lesions after intubation appear to be precursors of chronic lesions. OBJECTIVE: To describe the incidence and type of acute laryngeal lesions after extubation in a pediatric intensive care unit (PICU). METHODS: A cohort study involving children from birth to <5 years, submitted to intubation for more than 24h in the PICU of an university hospital. In the first eight hours after extubation, a flexible fiberoptic laryngoscopy (FFL) was performed at the bedside. Those with moderate to severe abnormalities underwent a second examination seven to ten days later. RESULTS: 177 patients were included, with a median age of 2.46 months. The mean intubation time was 8.19 days. Seventy-three (41.2%) patients had moderate or severe alterations at the FFL, with the remaining showing only minor alterations or normal results. During follow-up, 16 children from the group with moderate to severe lesions developed subglottic stenosis. One patient from the normal FFL group had subglottic stenosis, resulting in an incidence of 9.6% of chronic lesions. CONCLUSION: Most children in the study developed mild acute laryngeal lesions caused by endotracheal intubation, which improved in a few days after extubation. PMID- 26832635 TI - Comparison of nerve combing and percutaneous radiofrequency thermocoagulation in the treatment for idiopathic trigeminal neuralgia. AB - INTRODUCTION: Idiopathic trigeminal neuralgia (ITN) is a common pain disease in elderly people. Many methods have been used to alleviate the pain of patients, but few studies in the literature have compared the effect of nerve combing and percutaneous radiofrequency thermocoagulation. OBJECTIVE: The purpose of this study was to describe and evaluate the clinical outcome of idiopathic trigeminal neuralgia after nerve combing (NC) and compare them with those obtained using percutaneous radiofrequency thermocoagulation (RF). METHODS: The study included 105 idiopathic trigeminal neuralgia patients with similar symptom, age and underlying disease, which were divided into two groups. One group was treated by nerve combing (50 patients), the other by RF (55 cases). All patients were considered medical failures prior to the surgeries. A questionnaire was used to assess the long-term outcomes: pain relief, recurrence, complication and need for additional treatment. RESULTS: The median duration of follow-up in both groups was 90 months. Satisfactory relief was noted in 41 patients (82%), 5 patients (10%) initially experienced pain relief, then recurred, and four patients (8%) were designated poor among the group NC. In the group RF, satisfactory relief was noted in 42 patients (76.4%). There were eight "pain free with recurrence patients (14.5%) and 5 poor cases (9.1%). No statistically significant differences existed in the outcomes between both groups (p>0.05). Postoperative morbidity included dysesthesia, diplopia, partial facial nerve palsy, hearing loss, tinnitus, cerebrospinal fluid leak, meningitis and mortality. CONCLUSION: Nerve combing and RF are both satisfactory treatment strategies for patients with ITN. Because of the higher risk of sensory morbidity and surgical risk as open surgery, RF is preferred as the recommended procedure for patients with ITN. PMID- 26832636 TI - Epidemiological survey of mucus extravasation phenomenon at an oral pathology referral center during a 43 year period. AB - INTRODUCTION: Mucoceles are common benign pseudocystic lesions of the oral cavity; their main etiological factors are trauma and ductal obstruction. Two histological patterns are found: mucus retention phenomenon (MRP) and mucus extravasation phenomenon (MEP). Mucus extravasation phenomenon is the more common histological subtype and it mainly affects the lower lip. The knowledge of its main clinical features and management is important to assist health professionals in clinical practice. OBJECTIVE: This study aimed to determine the relative frequency and distribution of oral mucoceles in an oral pathology reference center. METHODS: Cross-sectional historical study that analyzed all cases pathologically diagnosed as mucus extravasation phenomenon by the department of anatomic pathology of an oral pathology referral center from June of 1970 to May of 2014, considering the clinical characteristics of the lesion and those relating to the patient. SPSS v. 20.0 software for Windows was used for descriptive analysis. RESULTS: During 43 years, 719 cases of mucus extravasation phenomenon (54.7% men and 45.3% women) were registered, with the lower lip as the most commonly affected site (n=484; 67.3%). The average age of patients was 20.8 years (SD+/-14.4) with a peak occurrence in the second decade of life. Most professionals had oral mucocele/ranula (n=606; 84.3%) as the initial clinical impression. CONCLUSION: Mucus extravasation phenomenon is a lesion that primarily affects young patients, affecting mainly the lower lip, and is commonly found in oral diagnostic services. PMID- 26832637 TI - Influence of the breathing pattern on the learning process: a systematic review of literature. AB - INTRODUCTION: Mouth breathing leads to negative consequences on quality of life, especially in school-age children. OBJECTIVE: To determine whether the breathing pattern influences children's learning process. METHODS: This systematic review was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) instructions, with no restrictions regarding the year of publication and language, created based on the clinical question formulation according to the Problem/Patient/Population, Intervention/Indicator, Comparison, Outcome (PICO) strategy: "Is the mouth-breathing child more likely to have learning disabilities when compared to nasal breathers?" in the SciELO, PubMed, LILACS, and Scopus electronic databases. Google Scholar was used to search the gray literature. The keywords "learning," "mouth breathing," and their equivalent terms in Portuguese were used in an integrated manner. The studies included in the review were observational, conducted with schoolchildren aged 7-11 years. Afterwards, the studies were evaluated regarding their methodological quality. The research was performed by two eligible reviewers. RESULTS: A total of 357 records were obtained, of which 43 records were duplicate. After applying the eligibility criteria, ten articles were included in the research scope. Half of the studies used a control group and otorhinolaryngological assessment, whereas a minority used validated (20%) and sample calculation protocols (10%). The evaluation procedures were varied. Overall, 80% of the articles showed a higher incidence of learning disabilities among mouth breathers. CONCLUSION: This systematic review has shown that mouth breathers are more likely to have learning difficulties than nasal breathers. PMID- 26832638 TI - Clinical evaluation for chin augmentation: literature review and algorithm proposal. AB - INTRODUCTION: The esthetic balance of the face results from harmonic and symmetrical facial proportions. The literature describes several methods for lower-third facial analysis, but lacks a simple and practical method. OBJECTIVE: To review the methods of analysis of the ideal projections of the chin based on soft tissues, showing the advantages and disadvantages of each. METHODS: Literature review through the PubMed database. RESULTS: The following methods for chin analysis based on soft tissues were reviewed: Gonzalles-Ulloa, Goode, Merrifield, Silver, Legan, Gibson & Calhoun, cervicomentual angle, and mentocervical angle. CONCLUSION: An adequate analysis of the proportions of the face and facial disharmony is essential for the correct indication of the necessary procedures and good surgical outcome. The authors propose an algorithm to facilitate the indication for chin augmentation surgery. PMID- 26832639 TI - Deciphering the Receptor Repertoire Encoding Specific Odorants by Time-Lapse Single-Cell Array Cytometry. AB - Mammals can recognize a vast number of odorants by using olfactory receptors (ORs) known as G protein-coupled receptors. The OR gene family is one of the most diverse gene families in mammalian genomes. Because of the vast combinations of ORs and odorants, few ORs have thus far been linked to specific odorants. Here, we established a functional screening method for OR genes by using a microchamber array containing >5,400 single olfactory epithelium-derived cells from mice applied to time-lapse single-cell array cytometry. This method facilitated the prompt isolation of single olfactory sensory neurons (OSNs) responding to the odorant of interest. Subsequent single-cell RT-PCR allowed us to isolate the genes encoding respective ORs. By using volatile molecules recognized as biomarkers for lung cancers, this method could deorphanize ORs and thereby reconstitute the OR-mediated signaling cascade in HEK293T cells. Thus, our system could be applied to identify any receptor by using specific ligands in the fields of physiopathology and pharmacology. PMID- 26832641 TI - Frontiers in microbial 1-butanol and isobutanol production. AB - The heavy dependence on petroleum-derived fuel has raised concerns about energy sustainability and climate change, which have prompted researchers to explore fuel production from renewable sources. 1-Butanol and isobutanol are promising biofuels that have favorable properties and can also serve as solvents or chemical feedstocks. Microbial production of these alcohols provides great opportunities to access a wide spectrum of renewable resources. In recent years, research has improved the native 1-butanol production and has engineered isobutanol production in various organisms to explore metabolic diversity and a broad range of substrates. This review focuses on progress in metabolic engineering for the production of these two compounds using various resources. PMID- 26832642 TI - Production and characterization of a Brazilian candidate antigen for Hepatitis E Virus genotype 3 diagnosis. AB - Hepatitis E, caused by hepatitis E virus (HEV), is a viral infectious pathology of great importance in the public health. Hepatitis E outbreaks were registered in developing countries with poor or no sanitation, where drinking water was contaminated with fecal material, but also in many industrialized countries probably due to consumption of HEV-positive swine meat. In this study, we present the development and characterization of a recombinant antigen from ORF2 HEV genotype 3. Viral RNA was extracted from swine feces infected with the native virus. A total of 267 residues from the C-terminal ORF2((394-661)) coding sequence were cloned into the pET20a vector and expressed in Escherichia coli ER2566. Recombinant protein was purified by liquid chromatography and the fragment obtained a 98% homology against other human or swine HEV genotype 3 ORF2 sequences. Wistar rats were inoculated with ORF2p, developing antibodies able to recognize both the homologous antigen and the native HEV genotype 3 ORF2 present in infected stool. In parallel, HEV-negative swine were experimentally challenged with HEV genotype 3. ORF2 was detected by PCR 14 days post-inoculation in three fourth piglets' feces and one week later by dot blot. In conclusion, this study proved the immunogenic and antigenic properties of the recombinant protein ORF2p. PMID- 26832643 TI - Permissiveness of freshly isolated environmental strains of amoebae for growth of Legionella pneumophila. AB - Legionella pneumophila is a pathogenic bacterium commonly found in water and responsible for severe pneumonia. Free-living amoebae are protozoa also found in water, which feed on bacteria by phagocytosis. Under favorable conditions, some L. pneumophila are able to resist phagocytic digestion and even multiply within amoebae. However, it is not clear whether L. pneumophila could infect at a same rate a large range of amoebae or if there is some selectivity towards specific amoebal genera or strains. Also, most studies have been performed using collection strains and not with freshly isolated strains. In our study, we assess the permissiveness of freshly isolated environmental strains of amoebae, belonging to three common genera (i.e. Acanthamoeba, Naegleria and Vermamoeba), for growth of L. pneumophila at three different temperatures. Our results indicated that all the tested strains of amoebae were permissive to L. pneumophila Lens and that there was no significant difference between the strains. Intracellular proliferation was more efficient at a temperature of 40 degrees C. In conclusion, our work suggests that, under favorable conditions, virulent strains of L. pneumophila could equally infect a large number of isolates of common freshwater amoeba genera. PMID- 26832644 TI - Phylogenetic diversity of rhizobial species and symbiovars nodulating Phaseolus vulgaris in Iran. AB - The phylogenetic diversity of 29 rhizobial strains nodulating Phaseolus vulgaris in Iran was analysed on the basis of their core and symbiotic genes. These strains displayed five 16S rRNA-RFLP patterns and belong to eight ERIC-PCR clusters. The phylogenetic analyses of 16S rRNA, recA and atpD core genes allowed the identification of several strains as Rhizobium sophoriradicis, R. leguminosarum, R. tropici and Pararhizobium giardinii, whereas other strains represented a new phylogenetic lineage related to R. vallis. These strains and those identified as R. sophoriradicis and R. leguminosarum belong to the symbiovar phaseoli carrying the gamma nodC allele distributed in P. vulgaris endosymbionts in America, Europe, Africa and Asia. The strain identified as R. tropici belongs to the symbiovar tropici carried by strains of R. tropici, R. leucaenae, R. lusitanum and R. freirei nodulating P. vulgaris in America, Africa and Asia. The strain identified as P. giardinii belongs to the symbiovar giardinii together with the type strain of this species nodulating P. vulgaris in France. It is remarkable that the recently described species R. sophoriradicis is worldwide distributed in P. vulgaris nodules carrying the gamma nodC allele of symbiovar phaseoli harboured by rhizobia isolated in the American distribution centers of this legume. PMID- 26832645 TI - Comparative study of bacterial translocation control with nitric oxide donors and COX2 inhibitor. AB - OBJECTIVE AND DESIGN: To evaluate the beneficial effects of exogenous NO and an inhibitor of the COX2, and their action levels in a model of SIRS/bacterial translocation (BT) induced by Zymosan A((r)). MATERIAL AND METHODS: Ninety Wistar rats were submitted to different treatments, and after 12h and 24h they were anaesthetized in order to collect blood, mesenteric lymph nodes, and kidney for subsequent biochemical analyses and microbiological examinations. TREATMENTS: A nitric oxide donor, Molsidomine((r)), was compared with a COX2 inhibitor, Celecoxib((r)). METHODS: Zymosan A((r)) was administered to Wistar rats. The animals were divided into 6 groups: one group for survival study, Group (1) No manipulation (BASAL); Group (2) vehicle of Zymosan A((r)) given intraperitoneally (SHAM); Group I (control), with Zymosan A((r)) (0.6g/kg) intraperitoneally; Group II (Molsidomine), with Molsidomine((r)) (4mg/kg) through the penis dorsal vein, 30min prior to administration of the Zy((r)) (0.6g/kg); Group III (Celecoxib), with Celecoxib((r)) (400mg/kg) orally through a stomach tube, 6h prior to administration of the Zy (0.6g/kg). DETERMINATIONS: The parameters survival, bacterial translocation, renal function, neutrophil accumulation, oxygen free radicals (OFR), detoxifying enzymes, and cytokines were measured at different times after Zymosan administration. RESULTS: The model established induced a mortality rate of 100% and generated BT and systemic inflammatory response syndrome (SIRS) in all samples. It also significantly increased all variables, with p<.001 for MPO and all pro-inflammatory cytokines, and p<.01 for all OFR. Treatment with Molsidomine reduced mortality to 0%, decreased BT, MPO, pro inflammatory cytokines and OFR (p<.001) significantly and increased IL-10 and IL 6 production. Moreover, the Celecoxib((r)) showed a lower capacity for SIRS regulation. CONCLUSIONS: The exogenous administration of NO prevented BT and controlled SIRS. Therefore these results suggest that Molsidomine could be used as a therapeutic strategy to protect against BT. PMID- 26832646 TI - Ozonated water is inferior to propanol-based hand rubs for disinfecting hands. AB - Ozone is a strong oxidizing biocide that has broad-spectrum antimicrobial properties. The aim of the study was to compare the efficacy of ozone to a propanol-based hand rub for hand disinfection. Twenty subjects were enrolled in an in-vivo cross-over trial (prEN 12791). Subjects treated their hands with the reference procedure (propan-1-ol 60%) or with ozone (4 ppm). Post-wash bacterial counts were determined from one hand (immediate effect), and from the other hand that had been gloved for 3h (delayed effect). The investigation indicated that ozone is inferior to propan-1-ol 60% hand rub for hand asepsis. PMID- 26832647 TI - Effectiveness of the CareCentre((r)) at improving contact precautions: randomized simulation and clinical evaluations. AB - BACKGROUND: Bedside hygiene is important to reduce healthcare-associated infection rates. The CareCentre((r)) is an end-of-hospital-bed table, housing: alcohol-based hand rub, gloves, aprons, waste bin, and an ergonomic writing surface. AIM: To determine the effectiveness of the CareCentre at improving bedside hygiene. METHODS: In the randomized cross-over simulation evaluation, 20 participants used the CareCentre and standard conditions to perform common bedside tasks. In the randomized cross-over clinical evaluation, nine pairs of acute adult hospital ward bays received CareCentres and standard conditions for one week each. Researchers measured adherence to the World Health Organization's 'my five moments for hand hygiene' and donning and disposing of gloves and aprons at the bedside. FINDINGS: Adherence to hand hygiene guidelines improved from 48% to 67% (P = 0.04) in the simulation and from 14% to 40% (P < 0.001) in the clinical evaluation. Donning and disposing of gloves at the bedside improved from 19% to 79% (P < 0.001) in the simulation and from 30% to 65% (P = 0.014) in the clinical evaluation. Donning and disposing of aprons at the bedside improved from 14% to 78% (P < 0.001) in the simulation and from 10% to 53% (P = 0.180) in the clinical evaluation. CONCLUSION: The CareCentre improved bedside hygiene and might help reduce healthcare-associated infection rates as part of a multimodal strategy. PMID- 26832648 TI - A visually detectable pH responsive zirconium metal-organic framework. AB - A halochromic Zr6-based metal-organic framework is synthesized using solvent assisted linker incorporation (SALI) with NU-1000 as a platform and carboxylnaphthofluorescein as a pH sensitive ligand. The functionalized MOF can catalytically detoxify nerve agent simulants in addition to visually detecting the acidic byproduct produced during detoxification. PMID- 26832649 TI - Feather eating and its associations with plumage damage and feathers on the floor in commercial farms of laying hens. AB - Feather eating has been associated with feather pecking, which continues to pose economic and welfare problems in egg production. Knowledge on feather eating is limited and studies of feather eating in commercial flocks of laying hens have not been performed previously. Therefore, the main objective was to investigate feather eating and its association with plumage damage and floor feather characteristics in commercial flocks of layers in barn and organic production systems. The study was performed in 13 flocks of barn layers and 17 flocks of organic layers. Each flock was visited at around 32 and 62 weeks of age. During both visits, the plumage condition was assessed and the density of floor feathers recorded. In week 62, droppings and floor feathers were collected. Droppings were examined for presence of feather content, whereas length, downiness and pecking damage were recorded for each floor feather. In week 62, a higher prevalence of hens with poor plumage condition was found in barn (22.2%) compared with organic production systems (7.4%; P<0.001), but the prevalence of droppings with feather content did not differ between the two production systems (8.5% in barn v. 4.3% in organic; P=0.99). Our hypothesis about a positive correlation between feather eating and plumage damage was not supported as no correlation was found between the prevalence of poor plumage condition and the prevalence of droppings with feather content. However, the prevalence of pecking damaged floor feathers was positively correlated both with prevalence of droppings with feather content (P<0.05) and poor plumage condition (P<0.01), indicating a possible association between feather eating and feather pecking. In conclusion, it was confirmed that feather eating occurs on-farm, but feather eating was only found to be positively correlated to the number of floor feathers with pecking damage and not as expected to the prevalence of plumage damage. More research is needed into the sources from where feathers are selected for ingestion, that is, whether they are picked from the floor litter, plucked directly from other hens or dislodged during preening of own feathers. PMID- 26832650 TI - Simeprevir and Sofosbuvir (SMV-SOF) for 12 Weeks for the Treatment of Chronic Hepatitis C Genotype 1 Infection: A Real World (Transplant) Hepatology Practice Experience. AB - OBJECTIVES: The combination of simeprevir (SMV) and sofosbuvir (SOF) was found to be well-tolerated with high sustained virologic response (SVR) rates in patients with genotype 1 chronic hepatitis C in clinical trials. Previous experience with hepatitis C virus (HCV) therapy has shown that patient tolerability and treatment efficacy described in controlled clinical trials did not necessarily mirror the "real world" experience. The goal of this study was to define SVR rates in a "real world" analysis and to explore predictors of treatment response with SMV and SOF. METHODS: This is a retrospective study examining the "real world" treatment of 170 patients with chronic HCV genotype 1 using the combination of SMV and SOF with or without ribavirin (RBV) for a fixed 12-week duration irrespective of prior interferon therapy, transplant status or fibrosis stage. Differences between SVR cohorts were analyzed by both intention-to-treat (ITT) and per protocol. RESULTS: The vast majority of patients were genotype 1a, 77% were cirrhotic in the non-LT group, and 35% of the entire cohort was African American. Combination treatment with SMV and SOF in genotype 1 chronic HCV patients achieved an overall SVR rate at 12 weeks after completion of therapy (SVR12) of 78% by ITT and 86% by per protocol (84% in non-liver transplant (LT) patients and 89% in post-LT recipients). The presence of hepatocellular carcinoma was found to be a significant negative predictor of SVR12, whereas an undetectable week eight VL was a significant positive predictor of SVR in the entire cohort. CONCLUSIONS: Our data confirm excellent SVR outcomes with favorable safety and tolerability profiles in patients who carry many traditional high-risk features for non-response, including post-LT recipients and patients with advanced liver disease. PMID- 26832652 TI - Neurological Dysfunction in Coeliac Disease and Non-Coeliac Gluten Sensitivity. AB - OBJECTIVES: Non-coeliac gluten sensitivity (NCGS) refers to patients with primarily gastrointestinal symptoms without enteropathy that symptomatically benefit from gluten-free diet (GFD). Little is known about its pathophysiology, propensity to neurological manifestations, and if these differ from patients with coeliac disease (CD). We investigated the clinical and immunological characteristics of patients presenting with neurological manifestations with CD and those with NCGS. METHODS: We compared clinical, neurophysiological, and imaging data of patients with CD and NCGS presenting with neurological dysfunction assessed and followed up regularly over a period of 20 years. RESULTS: Out of 700 patients, 562 were included. Exclusion criteria included no bowel biopsy to confirm CD, no HLA type available, and failure to adhere to GFD. All patients presented with neurological dysfunction and had circulating anti gliadin antibodies. Out of 562 patients, 228 (41%) had evidence of enteropathy (Group 1, CD) and 334 (59%) did not (Group 2, NCGS). The most common neurological manifestations were cerebellar ataxia, peripheral neuropathy, and encephalopathy. There was a greater proportion of patients with encephalopathy in Group 1 and with a greater proportion of neuropathy in Group 2. The severity of ataxia did not differ between the two groups. Patients in Group 1 had more severe neuropathy. All patients from both groups responded to gluten-free diet. Anti tissue transglutaminase (TG2) antibodies were found in 91% of patients in Group 1 and in 29% of patients in Group 2. Comparison between those patients in Group 2 with HLA-DQ2/DQ8 and those without as well as those with positive TG2 compared with those with negative TG2 antibodies identified no differences within these subgroups. Serological positivity for TG6 antibodies was similar in the two groups (67 and 60%). CONCLUSIONS: The neurological manifestations of CD and NCGS are similar and equally responsive to a GFD suggestive of common pathophysiological mechanisms. PMID- 26832654 TI - Capnographic Monitoring of Moderate Sedation During Low-Risk Screening Colonoscopy Does Not Improve Safety or Patient Satisfaction: A Prospective Cohort Study. AB - OBJECTIVES: Appropriate monitoring during sedation has been recognized as vital to patient safety in procedures outside of the operating room. Capnography can identify hypoventilation prior to hypoxemia; however, it is not clear whether the addition of capnography improves safety or is cost effective during routine colonoscopy, a high volume, low-risk procedure. Our aim was to evaluate the value of EtCO2 monitoring during colonoscopy with moderate sedation. METHODS: We conducted a prospective study of sedation safety and patient satisfaction before and after the introduction of EtCO2 monitoring during outpatient colonoscopy with midazolam and fentanyl using the validated PROcedural Sedation Assessment Survey (PROSAS). Complications of sedation and PROSAS scores were compared among colonoscopies with and without capnography. RESULTS: A total of 966 patients participated in our study, 465 in the pre-EtCO2 group and 501 in the EtCO2 group. On multivariate analysis, patients and nurses reported higher levels of procedural discomfort after adoption of capnography (1.71 vs. 1.00, P<0.001). No serious adverse events were seen, and minor sedation-related adverse events occurred with similar frequency in both groups (8.2% pre-EtCO2 vs. 11.2% EtCO2, P=0.115). The cost of implementing EtCO2 in our unit was $40,169.95 and added $11.68 per case. CONCLUSIONS: Colonoscopy with moderate sedation is a low-risk procedure, and the addition of EtCO2 did not improve safety or patient satisfaction but did increase cost. These data suggest that routine capnography in this setting may not be cost effective and that EtCO2 might be reserved for patients at higher risk of adverse events. PMID- 26832653 TI - Levofloxacin Sequential Therapy vs Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori: A Randomized Trial. AB - OBJECTIVES: The efficacy of levofloxacin triple therapy has fallen below 80% in the second-line treatment of Helicobacter pylori (H. pylori). We aimed to assess whether the levofloxacin sequential therapy is more effective than levofloxacin triple therapy in the second-line treatment. METHODS: This open-label, randomized, multicenter trial was conducted between 2012 and 2015. H. pylori infected subjects who failed from clarithromycin-based regimens (N=600) were randomized (1:1) to receive levofloxacin sequential therapy (LS: lansoprazole and amoxicillin for the first 5 days, followed by lansoprazole, levofloxacin, and metronidazole for another 5 days) or levofloxacin triple therapy (LT: lansoprazole, amoxicillin, and levofloxacin for 10 days). Successful eradication was defined as negative (13)C-urea breath test at least 6 weeks after treatment. Our primary outcome was the eradication rate by intention-to-treat (ITT) and per protocol (PP) analyses. Antibiotic resistance was determined by agar dilution test. RESULTS: The prevalence of clarithromycin, levofloxacin, and metronidazole resistance was 60, 17.6, and 36.9%, respectively. The eradication rates of LS and LT were 84.3% (253/300) and 75.3% (226/300), respectively, in the ITT analysis (P=0.006) and 86.3% (253/293) and 78.8% (223/283), respectively, in the PP analysis (P=0.021). The efficacies of both LS and LT were affected by levofloxacin resistance. The secondary resistance of levofloxacin was 66.7 and 73.9% after LS and LT, respectively. The efficacies of LS and LT were not affected by the CYP2C19 polymorphism. CONCLUSIONS: Levofloxacin sequential therapy was more effective than levofloxacin triple therapy, and it is recommended in the second-line treatment for H. pylori ( TRIAL REGISTRATION NUMBER: NCT01537055). PMID- 26832655 TI - High Hope for Medical Marijuana in Digestive Disorders. PMID- 26832651 TI - ACG Clinical Guideline: Liver Disease and Pregnancy. AB - Consultation for liver disease in pregnant women is a common and oftentimes vexing clinical consultation for the gastroenterologist. The challenge lies in the need to consider the safety of both the expectant mother and the unborn fetus in the clinical management decisions. This practice guideline provides an evidence-based approach to common diagnostic and treatment challenges of liver disease in pregnant women. PMID- 26832656 TI - High-Resolution Manometry Improves the Diagnosis of Esophageal Motility Disorders in Patients With Dysphagia: A Randomized Multicenter Study. AB - OBJECTIVES: High-resolution manometry (HRM) might be superior to conventional manometry (CM) to diagnose esophageal motility disorders. We aimed to compare the diagnosis performed with HRM and CM and confirmed at 6 months in a multicenter randomized trial. METHODS: Patients with unexplained dysphagia were randomized to undergo either CM or HRM. Motility disorders were diagnosed using the Castell and Spechler classification for CM and the Chicago classification for HRM. Diagnosis confirmation was based on clinical outcome and response to treatment after 6 month follow-up. The initial diagnosis and percentage of confirmed diagnoses were compared between the two arms (CM and HRM). RESULTS: In total, 247 patients were randomized and 245 analyzed: 122 in the CM arm and 123 in the HRM arm. A manometric diagnosis was more frequently initially achieved with HRM than with CM (97% vs. 84%; P<0.01). Achalasia was more frequent in the HRM arm (26% vs. 12% in the CM arm; P<0.01) while normal examinations were more frequent in the CM arm (52% vs. 28% in the HRM arm; P<0.05). After follow-up, the initial diagnosis was confirmed in 89% of patients in the HRM arm vs. 81% in the CM arm (P=0.07). Finally, overall procedure tolerance was better with CM than with HRM (P<0.01). CONCLUSIONS: This randomized trial demonstrated an improved diagnostic yield for achalasia with HRM compared with CM. Diagnoses tended to be more frequently confirmed in patients who underwent HRM, suggesting that esophageal motility disorders could be identified earlier with HRM than with CM (ClinicalTrial.gov, NCT01284894). PMID- 26832657 TI - Clinical Models and Algorithms for the Prediction of Retinopathy of Prematurity: A Report by the American Academy of Ophthalmology. AB - OBJECTIVE: To assess the accuracy with which available retinopathy of prematurity (ROP) predictive models detect clinically significant ROP and to what extent and at what risk these models allow for the reduction of screening examinations for ROP. METHODS: A literature search of the PubMed and Cochrane Library databases was conducted last on May 1, 2015, and yielded 305 citations. After screening the abstracts of all 305 citations and reviewing the full text of 30 potentially eligible articles, the panel members determined that 22 met the inclusion criteria. One article included 2 studies, for a total of 23 studies reviewed. The panel extracted information about study design, study population, the screening algorithm tested, interventions, outcomes, and study quality. The methodologist divided the studies into 2 categories-model development and model validation-and assigned a level of evidence rating to each study. One study was rated level I evidence, 3 studies were rated level II evidence, and 19 studies were rated level III evidence. RESULTS: In some cohorts, some models would have allowed reductions in the number of infants screened for ROP without failing to identify infants requiring treatment. However, the small sample size and limited generalizability of the ROP predictive models included in this review preclude their widespread use to make all-or-none decisions about whether to screen individual infants for ROP. As an alternative, some studies proposed approaches to apply the models to reduce the number of examinations performed in low-risk infants. CONCLUSIONS: Additional research is needed to optimize ROP predictive model development, validation, and application before such models can be used widely to reduce the burdensome number of ROP screening examinations. PMID- 26832658 TI - Intravitreal Aflibercept Injection in Diabetic Macular Edema Patients with and without Prior Anti-Vascular Endothelial Growth Factor Treatment: Outcomes from the Phase 3 Program. AB - PURPOSE: To evaluate visual and anatomic outcomes after intravitreal aflibercept injection (IAI) versus laser in diabetic macular edema (DME) patients with and without prior anti-vascular endothelial growth factor (VEGF) treatment for DME. DESIGN: Post hoc analysis of eyes from 2 similarly designed, phase 3 trials, VISTA and VIVID. PARTICIPANTS: Patients (eyes) with DME with central involvement from VISTA (n = 461) and VIVID (n = 404). METHODS: Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or macular laser photocoagulation. MAIN OUTCOME MEASURES: This study reports exploratory outcomes through week 100. Analyses focused on VISTA because more patients received prior anti-VEGF therapy in VISTA (42.9%) versus VIVID (8.9%). RESULTS: Of 42.9% of patients in VISTA who received prior anti-VEGF treatment, 83.3% to 92.6% received >= 1 prior injections of bevacizumab, and 71.4% to 82.4% received bevacizumab only as prior anti-VEGF treatment for a duration ranging from 28 days to 3.9 years. In patients with prior anti-VEGF treatment, mean best-corrected visual acuity (BCVA) changes from baseline in the IAI 2q4, IAI 2q8, and laser groups were +10.4 letters, +10.5 letters, and -0.7 letters at week 52 and +10.9 letters, +10.8 letters, and -0.8 letters at week 100, respectively. Corresponding changes in patients without prior anti-VEGF treatment were +14.1 letters, +11.0 letters, and +0.9 letters at week 52 and +12.0 letters, +11.3 letters, and +2.1 letters at week 100. In patients with prior anti-VEGF treatment, mean reductions in central retinal thickness were 180.2 MUm, 192.2 MUm, and 90.9 MUm at week 52 and 180.1 MUm, 196.4 MUm, and 94.1 MUm at week 100. Corresponding reductions in patients without prior anti-VEGF treatment were 190.3 MUm, 175.7 MUm, and 61.0 MUm at week 52 and 200.0 MUm, 186.7 MUm, and 76.9 MUm at week 100. The most frequent serious ocular adverse event was vitreous hemorrhage (1.3%, 0.7%, and 1.9%, respectively). CONCLUSIONS: Visual and anatomic improvements over laser with both IAI regimens were significant and similar through week 100 in subgroups of patients in VISTA with and without prior anti-VEGF treatment for DME. PMID- 26832659 TI - Skin Patterns Associated with Upper Airway Infantile Haemangiomas: A Retrospective Multicentre Study. AB - The aim of this study was to define the skin patterns at high risk for upper airway infantile haemangioma. A retrospective multicentre French observational study was conducted between January 2006 and January 2015 and all confirmed airway haemangioma were included. Thirty-eight patients with airway haemangioma from 9 centres were included. Thirty-one patients had a cutaneous or mucosal haemangioma: 21 with a location considered at high risk for airway haemangioma (large segmental mandibular haemangioma), 4 with a very mild facial involvement (lower lip or S1 (frontotemporal segment according to Haggstrom and Frieden)) and 6 with either lesions of the neck or body, or association of both. We report here the largest cohort of airway haemangioma. A third of patients do not completely fit with the definition of the high-risk area of airway haemangioma. Segmental lower lip and neck involvement also seem to be very suggestive areas. Clinicians must be able to recognize these areas. PMID- 26832660 TI - Toxocara canis myelitis involving the lumbosacral region: a case report. AB - CONTEXT: Toxocara canis is a parasite known to cause visceral larva migrans. The infection rarely affects the central nervous system but there have been several reports of myelitis caused by visceral larva migrans due to Toxocara canis. In previous reported cases, the lesions were located in the thoracic or cervical spinal cord. To the best of our knowledge, this is the first report of a lesion involving the lumbosacral region. FINDINGS: A 60-year-old man developed weakness and dysesthesia in the lower limbs. The symptoms resolved spontaneously, but recurred after five months. One month later, the patient developed pollakiuria and constipation. He was a dog owner and frequently ate raw chicken meat and beef liver. Sagittal T2-weighted image (T2WI) showed swelling and hyperintensity in the spinal cord from T10 to the lumbosacral region and focal nodular enhancement on the posterior segment of the lumbar spinal cord. Blood cell counts showed slight eosinophilia and elevated serum immunoglobulin E level. Cerebrospinal fluid examination showed slight pleocytosis with eosinophilia. Enzyme-linked immunosorbent assay showed high levels of anti-Toxocara antibodies in the serum and cerebrospinal fluid. In addition, confirmatory test by Western blot was positive. The patient was initially treated with intravenous methylprednisolone with slight improvement in muscle weakness. Albendazole was added with a second course of intravenous methylprednisolone. The muscle weakness in the lower limbs improved considerably, and swelling and hyperintensity on T2WI almost disappeared. CONCLUSION: Our results suggest that Toxocara canis myelitis cannot be discounted even if the myelitis involves the lumbosacral region. PMID- 26832661 TI - Serum Adipsin Levels throughout Normal Pregnancy and Preeclampsia. AB - Adipsin is a protease produced at high levels by adipose tissue. It is involved in complement activation and metabolic control. The objective of this study was to determine the changes in adipsin levels during different stages of normal pregnancy, and its association with obstetric outcomes, such as preeclampsia. This nested case-control study in a longitudinal cohort included normal pregnant (n = 54) and preeclamptic (n = 18) women, both followed throughout pregnancy. Additionally, some of the normal pregnant women were followed up three months postpartum (n = 18). Healthy non-pregnant women were also studied during their menstrual cycle (n = 20). The results of this study show that in healthy non pregnant women, adipsin levels did not change significantly during the menstrual cycle. In normal pregnant women, adipsin levels were lower (p < 0.01) when compared with non-pregnant healthy women, but these serum levels increased again during postpartum (p < 0.001). Adipsin levels were significantly elevated in preeclamptic women in late pregnancy (P < 0.01). A significant correlation was not found between leptin and adipsin during the three periods of gestation studied in healthy pregnant and preeclamptic women. Our results suggest that adipsin may be involved in pregnancy-associated metabolic changes. Moreover, the increase of adipsin levels towards late gestation in preeclamptic women could be related to the pathophysiology of this disease. PMID- 26832662 TI - miR-126 Regulates Distinct Self-Renewal Outcomes in Normal and Malignant Hematopoietic Stem Cells. AB - To investigate miRNA function in human acute myeloid leukemia (AML) stem cells (LSC), we generated a prognostic LSC-associated miRNA signature derived from functionally validated subpopulations of AML samples. For one signature miRNA, miR-126, high bioactivity aggregated all in vivo patient sample LSC activity into a single sorted population, tightly coupling miR-126 expression to LSC function. Through functional studies, miR-126 was found to restrain cell cycle progression, prevent differentiation, and increase self-renewal of primary LSC in vivo. Compared with prior results showing miR-126 regulation of normal hematopoietic stem cell (HSC) cycling, these functional stem effects are opposite between LSC and HSC. Combined transcriptome and proteome analysis demonstrates that miR-126 targets the PI3K/AKT/MTOR signaling pathway, preserving LSC quiescence and promoting chemotherapy resistance. PMID- 26832664 TI - Molecular diversity and distribution of indigenous arbuscular mycorrhizal communities colonizing roots of two different winter cover crops in response to their root proliferation. AB - A clear understanding of how crop root proliferation affects the distribution of the spore abundance of arbuscular mycorrhizal fungi (AMF) and the composition of AMF communities in agricultural fields is imperative to identify the potential roles of AMF in winter cover crop rotational systems. Toward this goal, we conducted a field trial using wheat (Triticum aestivum L.) or red clover (Trifolium pratense L.) grown during the winter season. We conducted a molecular analysis to compare the diversity and distribution of AMF communities in roots and spore abundance in soil cropped with wheat and red clover. The AMF spore abundance, AMF root colonization, and abundance of root length were investigated at three different distances from winter crops (0 cm, 7.5 cm, and 15 cm), and differences in these variables were found between the two crops. The distribution of specific AMF communities and variables responded to the two winter cover crops. The majority of Glomerales phylotypes were common to the roots of both winter cover crops, but Gigaspora phylotypes in Gigasporales were found only in red clover roots. These results also demonstrated that the diversity of the AMF colonizing the roots did not significantly change with the three distances from the crop within each rotation but was strongly influenced by the host crop identity. The distribution of specific AMF phylotypes responded to the presence of wheat and red clover roots, indicating that the host crop identity was much more important than the proliferation of crop roots in determining the diversity of the AMF communities. PMID- 26832665 TI - The effect of the cwf14 gene of fission yeast on cell wall integrity is associated with rho1. AB - In all eukaryotic organisms, a wide range of morphologies are responsible for critical cellular function and development. In particular, the Rho GTPases, which are highly conserved from yeast to mammals, are key molecules in signaling pathways that control cell polarity processes and cell wall biosynthesis, which are fundamental aspects of morphogenesis. Therefore, using haploinsufficiency deletion mutants of the fission yeast Schizosaccharomyces pombe, we screened the slow-growing mutants and their morphogenesis, specifically focusing on regulation of their Rho GTPases. Based on this screening, we found that the cwf14 mutant of S. pombe exhibited the slow growth and abnormal phenotypes with an elongated cell shape and thicker cell wall when compared with wild-type cells. In particular, cells with the cwf14 deletion showed excessive Rho1 expression. However, the wildtype strain with ectopically expressed Rho1 did not exhibited any significant change in the level of cwf14, suggesting that cwf14 may act on the upstream of Rho1. Furthermore, the cells with a cwf14 deletion also have increased sensitivity to beta-glucanase, a cell wall-digesting enzyme, which is also seen in Rho1-overexpressing cells. Overall, our results suggest that the cwf14 plays a key role in fission yeast morphogenesis and cell wall biosynthesis and/or degradation possibly via the regulation of Rho1 expression. PMID- 26832663 TI - Biofilm dispersion in Pseudomonas aeruginosa. AB - In recent decades, many researchers have written numerous articles about microbial biofilms. Biofilm is a complex community of microorganisms and an example of bacterial group behavior. Biofilm is usually considered a sessile mode of life derived from the attached growth of microbes to surfaces, and most biofilms are embedded in self-produced extracellular matrix composed of extracellular polymeric substances (EPSs), such as polysaccharides, extracellular DNAs (eDNA), and proteins. Dispersal, a mode of biofilm detachment indicates active mechanisms that cause individual cells to separate from the biofilm and return to planktonic life. Since biofilm cells are cemented and surrounded by EPSs, dispersal is not simple to do and many researchers are now paying more attention to this active detachment process. Unlike other modes of biofilm detachment such as erosion or sloughing, which are generally considered passive processes, dispersal occurs as a result of complex spatial differentiation and molecular events in biofilm cells in response to various environmental cues, and there are many biological reasons that force bacterial cells to disperse from the biofilms. In this review, we mainly focus on the spatial differentiation of biofilm that is a prerequisite for dispersal, as well as environmental cues and molecular events related to the biofilm dispersal. More specifically, we discuss the dispersal-related phenomena and mechanisms observed in Pseudomonas aeruginosa, an important opportunistic human pathogen and representative model organism for biofilm study. PMID- 26832666 TI - Kinetic characterization of a novel acid ectophosphatase from Enterobacter asburiae. AB - Expression of acid ectophosphatase by Enterobacter asburiae, isolated from Cattleya walkeriana (Orchidaceae) roots and identified by the 16S rRNA gene sequencing analysis, was strictly regulated by phosphorus ions, with its optimal activity being observed at an inorganic phosphate concentration of 7 mM. At the optimum pH 3.5, intact cells released p-nitrophenol at a rate of 350.76 +/- 13.53 nmol of p-nitrophenolate (pNP)/min/10(8) cells. The membrane-bound enzyme was obtained by centrifugation at 100,000 * g for 1 h at 4 degrees C. p Nitrophenylphosphate (pNPP) hydrolysis by the enzyme follows "Michaelis-Menten" kinetics with V = 61.2 U/mg and K0.5 = 60 MUM, while ATP hydrolysis showed V = 19.7 U/mg, K0.5 = 110 MUM, and nH = 1.6 and pyrophosphate hydrolysis showed V = 29.7 U/mg, K0.5 = 84 MUM, and nH = 2.3. Arsenate and phosphate were competitive inhibitors with K i = 0.6 mM and K i = 1.8 mM, respectively. p-Nitrophenyl phosphatase (pNPPase) activity was inhibited by vanadate, while p hydroxymercuribenzoate, EDTA, calcium, copper, and cobalt had no inhibitory effects. Magnesium ions were stimulatory (K0.5 = 2.2 mM and nH = 0.5). Production of an acid ectophosphatase can be a mechanism for the solubilization of mineral phosphates by microorganisms such as Enterobacter asburiae that are versatile in the solubilization of insoluble minerals, which, in turn, increases the availability of nutrients for plants, particularly in soils that are poor in phosphorus. PMID- 26832667 TI - Crystal structure and modeling of the tetrahedral intermediate state of methylmalonate-semialdehyde dehydrogenase (MMSDH) from Oceanimonas doudoroffii. AB - The gene product of dddC (Uniprot code G5CZI2), from the Gram-negative marine bacterium Oceanimonas doudoroffii, is a methylmalonate-semialdehyde dehydrogenase (OdoMMSDH) enzyme. MMSDH is a member of the aldehyde dehydrogenase superfamily, and it catalyzes the NAD-dependent decarboxylation of methylmalonate semialdehyde to propionyl-CoA. We determined the crystal structure of OdoMMSDH at 2.9 A resolution. Among the twelve molecules in the asymmetric unit, six subunits complexed with NAD, which was carried along the protein purification steps. OdoMMSDH exists as a stable homodimer in solution; each subunit consists of three distinct domains: an NAD-binding domain, a catalytic domain, and an oligomerization domain. Computational modeling studies of the OdoMMSDH structure revealed key residues important for substrate recognition and tetrahedral intermediate stabilization. Two basic residues (Arg103 and Arg279) and six hydrophobic residues (Phe150, Met153, Val154, Trp157, Met281, and Phe449) were found to be important for tetrahedral intermediate binding. Modeling data also suggested that the backbone amide of Cys280 and the side chain amine of Asn149 function as the oxyanion hole during the enzymatic reaction. Our results provide useful insights into the substrate recognition site residues and catalytic mechanism of OdoMMSDH. PMID- 26832668 TI - TatC-dependent translocation of pyoverdine is responsible for the microbial growth suppression. AB - Infections are often not caused by a colonization of Pseudomonas aeruginosa alone but by a consortium of other bacteria. Little is known about the impact of P. aeruginosa on the growth of other bacteria upon coinfection. Here, cell-ree culture supernatants obtained from P. aeruginosa suppressed the growth of a number of bacterial strains such as Corynebacterium glutamicum, Bacillus subtilis, Staphylococcus aureus, and Agrobacterium tumefaciens, but had little effect on the growth of Escherichia coli and Salmonella Typhimurium. The growth suppression effect was obvious when P. aeruginosa was cultivated in M9 minimal media, and the suppression was not due to pyocyanin, a well-known antimicrobial toxin secreted by P. aeruginosa. By performing transposon mutagenesis, PA5070 encoding TatC was identified, and the culture supernatant of its mutant did not suppress the growth. HPLC analysis of supernatants showed that pyoverdine was a secondary metabolite present in culture supernatants of the wild-type strain, but not in those of the PA5070 mutant. Supplementation of FeCl2 as a source of iron compromised the growth suppression effect of supernatants and also recovered biofilm formation of S. aureus, indicating that pyoverdine-mediated iron acquisition is responsible for the growth suppression. Thus, this study provides the action of TatC-dependent pyoverdine translocation for the growth suppression of other bacteria, and it might aid understanding of the impact of P. aeruginosa in the complex community of bacterial species upon coinfection. PMID- 26832669 TI - Antibacterial metabolites from the Actinomycete Streptomyces sp. P294. AB - The Actinomycete strain P294 was isolated from soil and identified as Streptomyces sp. based upon the results of 16S rRNA sequence analysis. Three compounds obtained from the solid fermentation products of this strain have been determined by 1D, 2D NMR and HRMS experiments. These compounds include two new compounds angumycinones C (1) and D (2), and the known compound X-14881 E (3). All compounds were assayed for antibacterial and nematicidal activity. The results showed the three compounds had different degrees of inhibitory activity against several target bacteria but no significant toxicity against the nematode Caenorhabditis elegans. PMID- 26832670 TI - Inhibition of eukaryotic translation by tetratricopeptide-repeat proteins of Orientia tsutsugamushi. AB - Orientia tsutsugamushi, an obligate intracellular bacterium, is the causative agent of scrub typhus. The genome of Orientia tsutsugamushi has revealed multiple ORFs encoding tetratricopeptide-repeat (TPR) proteins. The TPR protein family has been shown to be involved in a diverse spectrum of cellular functions such as cell cycle control, transcription, protein transport, and protein folding, especially in eukaryotic cells. However, little is known about the function of the TPR proteins in O. tsutsugamushi. To investigate the potential role of TPR proteins in host-pathogen interaction, two oriential TPR proteins were expressed in E. coli and applied for GSTpull down assay. DDX3, a DEAD-box containing RNA helicase, was identified as a specific eukaryotic target of the TPR proteins. Since the RNA helicase is involved in multiple RNA-modifying processes such as initiation of translation reaction, we performed in vitro translation assay in the presence of GST-TPR fusion proteins by using rabbit reticulocyte lysate system. The TPR proteins inhibited in vitro translation of a reporter luciferase in a dose dependent manner whereas the GST control proteins did not. These results suggested TPR proteins of O. tsutsugamushi might be involved in the modulation of eukaryotic translation through the interaction with DDX3 RNA helicase after secretion into host cytoplasm. PMID- 26832671 TI - CT-guided implantation of (125)I seeds (permanent brachytherapy) for metastatic tumors of the hepatic portal system: Effectiveness and safety in 13 patients. AB - PURPOSE: To retrospectively evaluate the efficacy and safety of CT-guided implantation of (125)I seeds (permanent brachytherapy) for metastatic tumors of the hepatic portal system (HPS). METHODS AND MATERIALS: Between January 2012 and January 2015, 13 patients with metastases measuring >3.0 cm in short-axis diameter, which remained in the HPS after conventional chemotherapy and/or transcatheter arterial chemoembolization, and for which an effective therapeutic dose from external beam radiotherapy could not be delivered, received CT-guided (125)I brachytherapy. Clinical data were studied retrospectively. In terms of metrological requirements, the minimum dose to 90% of the target volume (D90) was 90-160 Gy for (125)I seeds with activity of 2.96 * 10(7)Bq. CT-based evaluation after 2, 4, and 8 weeks, as well as 6 months after implantation enabled review of local control of tumors. RESULTS: All symptoms were improved after (125)I brachytherapy. The mean value for D90 for implantation of (125)I seeds was 136 Gy. Complete response (CR) + partial response (PR) was documented in 61.5%, 69.2%, and 84.6% of patients at 2 weeks, 4 weeks, and 6 months after implantation, respectively. Four of 13 patients had complete response, 7 cases had PR, 1 patient had stable disease, and 1 case had progressive disease. All metastatic foci were controlled by implantation. No serious complications were observed. CONCLUSION: CT-guided (125)I brachytherapy is a safe and effective treatment for metastatic tumors of the HPS and can achieve good local control in the short term as long as the radiation dose is sufficient. CT-guided (125)I brachytherapy carries few complications, is simple, safe, and a good complement to cancer treatment. PMID- 26832672 TI - Concurrent chemobrachytherapy in locally advanced cervical carcinoma: A hypothesis worth exploring. PMID- 26832673 TI - Three-dimensional transrectal ultrasound guided high-dose-rate prostate brachytherapy: A comparison of needle segmentation accuracy with two-dimensional image guidance. AB - PURPOSE: Conventional transrectal ultrasound guided high-dose-rate prostate brachytherapy (HDR-BT) uses an axially acquired image set for organ segmentation and 2D sagittal images for needle segmentation. Sagittally reconstructed 3D (SR3D) transrectal ultrasound enables both organ and needle segmentation and has the potential to reduce organ-needle alignment uncertainty. This study compares the accuracy of needle tip localization between the conventional 2D sagittally assisted axially reconstructed (SAAR) and SR3D approaches. METHODS AND MATERIALS: Twelve patients underwent SAAR-guided HDR-BT, during which SR3D images were acquired for subsequent segmentation and analysis. A total of 183 needles were investigated. Needle end-length measurements were taken, providing a gold standard for insertion depths. Dosimetric impact of insertion depth errors (IDEs) on clinical treatment plans was assessed. RESULTS: SR3D guidance provided statistically significantly smaller IDEs than SAAR guidance with a mean +/- SD of -0.6 +/- 3.2 mm and 2.8 +/- 3.2 mm, respectively (p < 0.001). Shadow artifacts were found to obstruct the view of some needle tips in SR3D images either partially (12%) or fully (10%); however, SR3D IDEs had a statistically significantly smaller impact on prostate V100% than SAAR IDEs with mean +/- SD decreases of -1.2 +/- 1.3% and -6.5 +/- 6.7%, respectively (p < 0.05). CONCLUSIONS: SR3D-guided HDR-BT eliminates a source of systematic uncertainty from the SAAR-guided approach, providing decreased IDEs for most needles, leading to a significant decrease in dosimetric uncertainty. Although imaging artifacts can limit the accuracy of tip localization in a subset of needles, we identified a method to mitigate these artifacts for clinical implementation. PMID- 26832674 TI - Lessons learned using an MRI-only workflow during high-dose-rate brachytherapy for prostate cancer. AB - PURPOSE: We report clinical observations of a technique using an MRI-only workflow for catheter insertion and treatment planning in patients receiving standard-care high-dose-rate brachytherapy before external beam radiotherapy for prostate cancer. METHODS AND MATERIALS: Forty patients with intermediate or high risk prostate cancer were enrolled on a prospective clinical trial approved by our institution's research ethics board. Multiparametric MRI with stereotactic navigation was used to guide insertion of brachytherapy catheters, followed by MRI-based treatment planning. RESULTS: Sixty-two implants were performed. Median catheter insertion + imaging time was 100 minutes, and overall anesthesia time was 4.0 hours (range, 2.1-6.9 hours). MRI at the time of brachytherapy restaged 14 patients (35%) who were found to have a higher stage of disease. In 6 patients, this translated in directed insertion of brachytherapy catheters outside the prostate boundary (extracapsular disease [n = 2] or seminal vesicle invasion [n = 4]). Most patients (80%) had gross tumor visible on MRI, which influenced catheter insertion and treatment planning. MRI depicted postimplant anatomic boundaries clearly, with the exception of the apical prostate which was blurred by trauma after catheter insertion. Conventional dose-planning objectives for the rectum (V75 < 1.0 cc) were difficult to achieve, but toxicities were low (acute grade >= 2 genitourinary = 20%, late grade >= 2 genitourinary = 15%, and late grade >= 2 gastrointestinal = 7%). Urethral trauma visualized on MRI led to two transient Grade 3 events. CONCLUSIONS: Despite a standard-care approach, MRI acquired throughout the procedure altered catheter insertion and dose-planning strategies. An MRI-only workflow is feasible but must be streamlined for broader acceptance. PMID- 26832676 TI - In response to Kirisits, Schmid, Beriwal, and Potter. PMID- 26832675 TI - The impact of trainee involvement on outcomes in low-dose-rate brachytherapy for prostate cancer. AB - PURPOSE: To determine the impact of fellow, resident, or medical student (MS) involvement on outcomes in patients undergoing permanent (125)I prostate seed implant. METHODS AND MATERIALS: The study population consisted of men with clinically localized low/intermediate-risk prostate cancer treated with low-dose rate permanent interstitial brachytherapy. Cases were stratified according to resident, fellow, MS, or attending involvement. Outcomes were compared using analysis of variance, logistic regression, and log rank tests. RESULTS: A total of 291 patients were evaluated. Fellows, residents, and MS were involved in 47 (16.2%), 231 (79.4%), and 34 (11.7%) cases, respectively. Thirteen (4.4%) cases were completed by an attending physician alone. There was no difference in freedom from biochemical failure when comparing the resident, fellow, or attending alone groups (p = 0.10). There was no difference in V100 (volume of the prostate receiving 100% of the prescription dose) outcomes when comparing resident cases to fellow cases (p = 0.72) or attending alone cases (p = 0.78). There was no difference in D90 (minimum dose covering 90% of the postimplant volume) outcomes when comparing resident cases to fellow cases (p = 0.74) or attending alone cases (p = 0.58). When examining treatment toxicity, fellow cases had higher rates of acute Grade 2 + GU toxicity (p = 0.028). With the exception of higher urethra D90 among PGY 2-3 cases (p = 0.02), dosimetric outcomes were similar to cases with PGY 4-5 resident participation. There was no difference in outcomes for cases with and without MS participation. CONCLUSIONS: Interstitial prostate seed implants can be safely performed by trainees with appropriate supervision. Hands-on brachytherapy training is effective and feasible for trainees. PMID- 26832677 TI - Dose escalation with external beam radiation therapy and high-dose-rate brachytherapy combined with long-term androgen deprivation therapy in high and very high risk prostate cancer: Comparison of two consecutive high-dose-rate schemes. AB - PURPOSE: To compare rectal toxicity, urinary toxicity, and nadir+2 PSA relapse free survival (bRFS) in two consecutive Phase II protocols of high-dose-rate (HDR) brachytherapy used at the authors institution from 2001 to 2012. METHODS AND MATERIALS: Patients with National Comprehensive Cancer Network high risk and very high risk prostate cancer enrolled in studies HDR4 (2001-2007, n = 183) and HDR2 (2007-2012, n = 56) were analyzed. Patients received minipelvis external beam radiation therapy/intensity-modulated external radiotherapy to 54 Gy and 2 years of androgen blockade along with HDR brachytherapy. HDR4 protocol consisted of four 4.75 Gy fractions delivered in 48 hours; the HDR2 protocol delivered two 9.5 Gy fractions in 24 hours. Average 2-Gy equivalent dose (alpha/beta = 1.2) prostate D90 doses for the HDR4 and HDR2 groups were 89.8 Gy and 110.5 Gy, respectively (p = 0.0001). Both groups were well balanced regarding risk factors. Prior transurethral resection of the prostate was more frequent in the HDR2 group (p = 0.001). RESULTS: After a median followup of 7.4 years (range, 2-11.2), there was no difference in adverse grade >= 2 rectal events (HDR4 = 10.4% vs. HDR2 = 12.5%; p = ns) or grade >=3 (HDR4 = 2.2% vs. HDR2 = 3.6%; p = ns). No differences in urinary grade >=2 adverse events (HDR4 = 23% vs. HDR2 = 26.8%; p = ns) or grade >=3 (HDR4 = 7.7% vs. HDR2 = 8.9%; p = ns) were detected. The 7-year bRFS for HDR4 and HDR2 protocols was 88.7% and 87.8%, respectively (p = ns). CONCLUSIONS: HDR4 and HDR2 protocols produce similar results in terms of toxicity and bRFS at the intermediate time point of 7 years. PMID- 26832678 TI - Detection of Klebsiella. Pneumoniae Infection with an Antisense Oligomer Against its Ribosomal RNA. AB - PURPOSE: Previously, we demonstrated specific accumulation into bacteria of a 12 mer phosphorodiamidate morpholino (MORF) oligomer complementary to a ribosomal RNA (rRNA) segment found in all bacteria using the universal probe called Eub338 (Eub). Here, two MORF oligomers Eco and Kpn with sequences specific to the rRNA of Escherichia coli (Eco) and Klebsiella pneumoniae (Kpn) were investigated along with Eub and control (nonEub). PROCEDURES: To determine bacterial rRNA binding, oligomers were tagged with Alexa Fluor 633 (AF633) for fluorescence in situ hybridization (FISH) and fluorescence microscopy, and radiolabeled with technetium-99m (Tc-99m) for biodistribution and SPECT imaging in infected mice. RESULTS: By both FISH and fluorescence microscopy, Eub showed a positive signal in both E. coli and K. pneumoniae as expected, and Kpn showed significantly higher accumulation in K. pneumoniae with near background in E. coli (p < 0.01). Conversely, Eco was positive in both E. coli and K. pneumoniae, hence nonspecific. As determined by biodistribution, the accumulation of [(99m)Tc]Kpn was higher in the thigh infected with live K. pneumoniae than with live E. coli (p = 0.05), and significantly higher than with heat-killed K. pneumoniae (p = 0.02) in the target thigh. By SPECT imaging, the accumulation of [(99m)Tc]Kpn was obviously higher in its specific target of K. pneumoniae compared to an E. coli infected thigh. CONCLUSIONS: Kpn complementary to the rRNA of K. pneumoniae, labeled with Tc-99m or AF633, demonstrated specific binding to fixed and live K. pneumoniae in culture and in infected mice such that Tc-99m-labeled Kpn as the MORF oligomer may be useful for K. pneumoniae infection detection through imaging. PMID- 26832679 TI - Tissue Dissociation for Metastasis Studies. AB - The main requirement for most metastasis-related applications is the conversion of solid tissue into a single-cell suspension. In theory, this suspension represents the diversity of cells present in the tissue, whether malignant or benign. We have found that cell viability, as measured by trypan blue staining or fluorescence-activated cell sorting (FACS), is critical for evaluating the success of the tissue-dissociation procedure. The recommended goal is at least 70% cell viability. PMID- 26832680 TI - Murine Stem Cell-Based Retrovirus Production for Marking Primary Mouse Mammary Cells for Metastasis Studies. AB - Since the introduction of retroviral vector technology, permanent genetic marking of cells has considerably contributed to the understanding of different physiological and disease processes in vivo. Recent marking strategies aim to elucidate the contribution of cells on the clonal level, and the advent of fluorescent proteins has opened new avenues for the in vivo analysis of gene marked cells. Gene-modified cells are easily identifiable (e.g., via the introduced fluorescent protein) within whole organ structures, allowing one to measure the contribution of transduced cells to malignant outgrowth. In our laboratory, we use the tetracycline-inducible system to study oncogene cooperation in metastatic progression. We use bicistronic retroviruses expressing the tetracycline transactivator (tTA) and the candidate gene (MIT-gene) or the tTA alone (MIT-Rx) to infect primary mammary cells from mice harboring tetracycline-inducible transgenes. This allows for constitutive expression of the candidate gene and tTA-dependent expression of the inducible oncogene. We also use MIG-based vectors, which allow for constitutive expression of the candidate gene and a green fluorescent protein. Here we describe how to produce retroviral particles carrying both MIT- and MIG-based vectors. Because of the fragility of the retroviral envelope, we do not attempt to concentrate the virus, and we directly use packaging cell media to infect primary epithelial cells (either normal or tumor). Infected cells can be transplanted into recipient mice to investigate metastatic colonization. PMID- 26832681 TI - Enrichment of Mammary Basal and Luminal Cells for Cell-of-Origin Metastasis Studies. AB - The mammary gland is an important model system in metastasis research. Mammary epithelial stem cells are of particular interest because of their capacity for regeneration and their role in cancer initiation. This protocol describes how to enrich for mammary basal and luminal epithelial cells using fluorescence activated cell sorting (FACS). PMID- 26832682 TI - Complete Membrane Fractionation of 3T3-L1 Adipocytes. AB - Fractionation techniques can facilitate the isolation of intracellular organelles containing insulin-sensitive glucose transporter isoform 4 (GLUT4), which is mobilized from GLUT4 storage vesicles in fat and muscle cells in response to insulin. This protocol for the full membrane fractionation of 3T3-L1 adipocytes results in five distinct fractions. A heavy membrane-containing pellet is produced and then further separated into the plasma membrane, mitochondrial and nuclear, and high-density membrane fractions. The initial supernatant is subjected to a series of centrifugation steps to isolate the low-density membrane fraction, which contains the majority of the insulin-sensitive pool of GLUT4; the supernatant produced in this step is the soluble fraction. The distribution of GLUT4 in fractions from insulin-stimulated versus untreated cells is assessed via immunoblotting. PMID- 26832683 TI - Iodixanol Gradient Centrifugation to Separate Components of the Low-Density Membrane Fraction from 3T3-L1 Adipocytes. AB - We optimized a set of fractionation techniques to facilitate the isolation of subcellular compartments containing insulin-sensitive glucose transporter isoform 4 (GLUT4), which is mobilized from GLUT4 storage vesicles (GSVs) in fat and muscle cells in response to insulin. In the absence of insulin, GLUT4 undergoes a continuous cycle of GSV formation and fusion with other compartments. Full membrane fractionation of 3T3-L1 adipocytes produces a low-density membrane fraction that contains both the constitutive recycling pool (the endosomal recycling compartments) and the insulin-sensitive pool (the GSVs). These two pools can be separated based on density using iodixanol gradient centrifugation, described here. PMID- 26832684 TI - Analysis of Replicating Yeast Chromosomes by DNA Combing. AB - Molecular combing of DNA fibers is a powerful technique to monitor origin usage and DNA replication fork progression in the budding yeast Saccharomyces cerevisiae. In contrast to traditional flow cytometry, microarray, or sequencing techniques, which provide population-level data, DNA combing provides DNA replication profiles of individual molecules. DNA combing uses yeast strains that express human thymidine kinase, which facilitates the incorporation of thymidine analogs into nascent DNA. First, DNA is isolated and stretched uniformly onto silanized glass coverslips. Following immunodetection with antibodies that recognize the thymidine analog and the DNA, the DNA fibers are imaged using a fluorescence microscope. Finally, the lengths of newly replicated DNA tracks are measured and converted to base pairs, allowing calculations of the speed of the replication fork and of interorigin distances. DNA combing can be applied to monitor replication defects caused by gene mutations or by chemical agents that induce replication stress. Here, we present a methodology for studying replicating yeast chromosomes by molecular DNA combing. We begin with procedures for the preparation of silanized coverslips and for assembly of a DNA combing machine (DCM) and conclude by presenting a detailed protocol for molecular DNA combing in yeast. PMID- 26832685 TI - Detection of Autophagy in Caenorhabditis elegans by Western Blotting Analysis of LGG-1. AB - A common way to measure the induction of autophagy in yeast and mammalian cells is to compare the amount of Atg8/LC3-I with that of Atg8-PE/LC3-II by using western blot analysis. This is because changes in the amount of LC3-II correlate closely with changes in the number of autophagosomes present in cells. Atg8/LC3 is initially synthesized as an unprocessed form, which is proteolytically processed to form Atg8/LC3-I, and then this is modified into the phosphatidylethanolamine (PE)-conjugated Atg8-PE/LC3-II form. Atg8/LC3-II is membrane bound, whereas Atg8-PE/LC3-I is cytosolic. By associating with both the inner and outer membranes of the autophagosome, Atg8-PE/LC3-II is the only autophagy reporter that is reliably associated with completed autophagosomes. In the nematode Caenorhabditis elegans, the ortholog of Atg8/LC3 is LGG-1. Here, we discuss how changes in the levels of LGG-1-II (and the paralog LGG-2) protein can, with appropriate controls, be used to monitor autophagy activity in nematodes and present a protocol for monitoring changes in the protein levels of different forms of LGG-1 by western blotting. PMID- 26832686 TI - RNAi-Mediated Inactivation of Autophagy Genes in Caenorhabditis elegans. AB - RNA interference (RNAi) is a process that results in the sequence-specific silencing of endogenous mRNA through the introduction of double-stranded RNA (dsRNA). In the nematode Caenorhabditis elegans, RNA inactivation can be used at any specific developmental stage or during adulthood to inhibit a given target gene. Investigators can take advantage of the fact that, in C. elegans, RNAi is unusual in that it is systemic, meaning that dsRNA can spread throughout the animal and can affect virtually all tissues except neurons. Here, we describe a protocol for the most common method to achieve RNAi in C. elegans, which is to feed them bacteria that express dsRNA complementary to a specific target gene. This method has various advantages, including the availability of libraries that essentially cover the whole genome, the ability to treat animals at any developmental stage, and that it is relatively cost effective. We also discuss how RNAi specific to autophagy genes has proven to be an excellent method to study the role of these genes in autophagy, as well as other cellular and developmental processes, while also highlighting the caveats that must be applied. PMID- 26832688 TI - Generation of Genetically Modified Mice Using the CRISPR-Cas9 Genome-Editing System. AB - Genetically modified mice are extremely valuable tools for studying gene function and human diseases. Although the generation of mice with specific genetic modifications through traditional methods using homologous recombination in embryonic stem cells has been invaluable in the last two decades, it is an extremely costly, time-consuming, and, in some cases, uncertain technology. The recently described CRISPR-Cas9 genome-editing technology significantly reduces the time and the cost that are required to generate genetically engineered mice, allowing scientists to test more precise and bold hypotheses in vivo. Using this revolutionary methodology we have generated more than 100 novel genetically engineered mouse strains. In the current protocol, we describe in detail the optimal conditions to generate mice carrying point mutations, chromosomal deletions, conditional alleles, fusion tags, or endogenous reporters. PMID- 26832687 TI - Calling Card Analysis in Budding Yeast. AB - Calling card analysis is a high-throughput method for identifying the genomic binding sites of multiple transcription factors in a single experiment in budding yeast. By tagging a DNA-binding protein with a targeting domain that directs the insertion of the Ty5 retrotransposon, the genomic binding sites for that transcription factor are marked. The transposition locations are then identified en masse by Illumina sequencing. The calling card protocol allows for simultaneous analysis of multiple transcription factors. By cloning barcodes into the Ty5 transposon, it is possible to pair a unique barcode with every transcription factor in the experiment. The method presented here uses expression of transcription factors from their native loci; however, it can also be altered to measure binding sites of transcription factors overexpressed from a plasmid. PMID- 26832689 TI - Methods to Study Metastasis in Genetically Modified Mice. AB - Metastasis is often modeled by xenotransplantation of cell lines in immunodeficient mice. A wealth of information about tumor cell behavior in the new environment is obtained from these efforts. Yet by design, this approach is "tumor-centric," as it focuses on cell-autonomous determinants of human tumor dissemination in mouse tissues, in effect using the animal body as a sophisticated "Petri dish" providing nutrients and support for tumor growth. Transgenic or gene knockout mouse models of cancer allow the study of tumor spread as a systemic disease and offer a complimentary approach for studying the natural history of cancer. This introduction is aimed at describing the overall methodological approach to studying metastasis in genetically modified mice, with a particular focus on using animals with regulated expression of potent human oncogenes in the breast. PMID- 26832690 TI - Detection of Autophagy in Caenorhabditis elegans. AB - Autophagy is a dynamic and catabolic process that results in the breakdown and recycling of cellular components through the autophagosomal-lysosomal pathway. Many autophagy genes identified in yeasts and mammals have orthologs in the nematode Caenorhabditis elegans. In recent years, gene inactivation by RNA interference (RNAi) and chromosomal mutations has been useful to probe the functions of autophagy in C. elegans, and a role for autophagy has been shown to contribute to multiple processes, such as the adaptation to stress, longevity, cell death, cell growth control, clearance of aggregation-prone proteins, degradation of P granules during embryogenesis, and apoptotic cell clearance. Here, we discuss some of these roles and describe methods that can be used to study autophagy in C. elegans. Specifically, we summarize how to visualize autophagy in embryos, larva, or adults, how to detect the lipidation of the ubiquitin-like modifier LGG-1 by western blot, and how to inactivate autophagy genes by RNAi. PMID- 26832691 TI - Transposon Calling Cards. AB - Identifying the genomic targets of transcription factors is an important step in understanding the regulatory networks of gene transcription in yeast. We have developed a method that utilizes what we refer to as transposon "calling cards," in which a transcription factor directs the Ty5 retrotransposase to insert transposons into the genome adjacent to where the transcription factor binds. This method is designed to be multiplexed with many barcoded transcription factors and has the potential to decrease the labor required for the study of large numbers of transcription factors. PMID- 26832692 TI - Single-Molecule Analysis of Replicating Yeast Chromosomes. AB - The faithful replication of eukaryotic chromosomal DNA occurs during S phase once per cell cycle. Replication is highly regulated and is initiated at special structures, termed origins, from which replication forks move out bidirectionally. A wide variety of techniques have been developed to study the features and kinetics of replication. Many of these, such as those based on flow cytometry and two-dimensional and pulsed-field gel electrophoresis, give a population-level view of replication. However, an alternative approach, DNA fiber analysis, which was originally developed more than 50 years ago, has the advantage of revealing features of replication at the level of individual DNA fibers. Initially based on autoradiography, this technique has been superseded by immunofluorescence-based detection of incorporated halogenated thymidine analogs. Furthermore, derivations of this technique have been developed to distribute and stretch the labeled DNA fibers uniformly on optically clear surfaces. As described here, one such technique-DNA combing, in which DNA is combed onto silanized coverslips-has been used successfully to monitor replication fork progression and origin usage in budding yeast. PMID- 26832693 TI - Editing the Mouse Genome Using the CRISPR-Cas9 System. AB - The ability to modify the murine genome is perhaps one of the most important developments in modern biology. However, traditional methods of genomic engineering are costly and relatively clumsy in their approach. The use of programmable nucleases such as zinc finger nucleases and transcription activator like effector nucleases significantly improved the precision of genome-editing technology, but the design and use of these nucleases remains cumbersome and prohibitively expensive. The CRISPR-Cas9 system is the next installment in the line of programmable nucleases; it provides highly efficient and precise genome editing capabilities using reagents that are simple to design and inexpensive to generate. Furthermore, with the CRISPR-Cas9 system, it is possible to move from a hypothesis to an in vivo mouse model in less than a month. The simplicity, cost effectiveness, and speed of the CRISPR-Cas9 system allows researchers to tackle questions that otherwise would not be technically or financially viable. In this introduction, we discuss practical considerations for the use of Cas9 in genome engineering in mice. PMID- 26832694 TI - El Nino, Climate, and Cholera Associations in Piura, Peru, 1991-2001: A Wavelet Analysis. AB - In Peru, it was hypothesized that epidemic cholera in 1991 was linked to El Nino, the warm phase of El Nino-Southern Oscillation. While previous studies demonstrated an association in 1997-1998, using cross-sectional data, they did not assess the consistency of this relationship across the decade. Thus, how strong or variable an El Nino-cholera relationship was in Peru or whether El Nino triggered epidemic cholera early in the decade remains unknown. In this study, wavelet and mediation analyses were used to characterize temporal patterns among El Nino, local climate variables (rainfall, river discharge, and air temperature), and cholera incidence in Piura, Peru from 1991 to 2001 and to estimate the mediating effects of local climate on El Nino-cholera relationships. The study hypothesis is that El Nino-related connections with cholera in Piura were transient and interconnected via local climate pathways. Overall, our findings provide evidence that a strong El Nino-cholera link, mediated by local hydrology, existed in the latter part of the 1990s but found no evidence of an El Nino association in the earlier part of the decade, suggesting that El Nino may not have precipitated cholera emergence in Piura. Further examinations of cholera epicenters in Peru are recommended to support these results in Piura. For public health planning, the results may improve existing efforts that utilize El Nino monitoring for preparedness during future climate-related extremes in the region. PMID- 26832695 TI - [Preliminary study on the biological effects of MiR-144 in pulmonary injury in rats induced by nanosized SiO2]. AB - OBJECTIVE: To Investigate the biological effects of miR-144 in rats' pulmanory injury induced by nanosized SiO2preliminarily. METHOD: 150 healthy SD rats were divided into five groups randomly: the control group, the nanosized SiO2groups of 6.25, 12.5, 25.0 mg/ml, and the microsized SiO2group of 25.0 mg/ml, 30 rats each group. Six rats were sacrificed for their pathological change on the 7th, 15th, 30th, 60th and 90th day after exposure. The expression levels of mature miR-144 in lung tissue of the rats after instilled intracheally nanosized SiO2at 90d was detected by Quantitative Reverse Transcription PCR. Target prediction for miR-144 was conducted by databases of Target-scan, microRNA.org and miRDB. Function significant enrichment analysis and signal pathway analysis for predicted target genes were respectively conducted by the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes, then target genes related to pulmonary fibrosis were screened out. RESULTS: The expression of miR-144 was up-regulated in lung tissue of rats exposed to nanosized SiO2. The result was consistent with the results of high-throughput sequencing Hiseq 2000. The target genes of miR-144 related to fibrosis or signal pathway involved in fibrosis were screened out.They are SMAD4, SMAD5, ADAMTS3, ADAMTS15 and ADAMTS19. CONCLUSION: MiR-144 probably participate in the regulation of fibrosis, which may play an important role in pulmonary injury induced by nanosized SiO2. PMID- 26832696 TI - [The effect of signal transduction pathway of triggering receptor-1 expressed on myeloid cells in acute lung injury induced by paraquat in rats]. AB - OBJECTIVE: To investigate the transduction pathway of triggering receptor-1 expressed on myeloid cells (TREM-1) in acute lung injure induced by paraquat in rats through the activating or blocking TREM-1, to observe the effect of signal transduction pathway in the acute lung injure induced-paraquat. METHODS: 80 SD rats were randomly divided into normal saline control group (n=20) , PQ poisoning group (n=20) , antibody group (n=20) , and LP17 group (n=20). poisoning group, antibody group and LP17 group were given saline diluting PQ 80 mg/kg of disposable lavage after 2 h, a single set of intraperitoneal injection of anti TREM-1 mAb (250 g/kg) , tail intravenous LP17 group synthetic peptide (3.5 mg/kg) , poisoning group was given equal normal saline intraperitoneal injection, control group given normal saline 1 mg/kg after 2 h after lavage, given the amount of intraperitoneal injection of saline solution. The expression of NF kappaB in lung tissue was determined by immunohistochemistry.The levels of TNF-a, IL-10, TREM-1, and soluble TREM-1 (sTREM-1) in lung tissue and serum were measured by ELISA. Pathology changes of lung were observed under light microscope, and lung score of pathology was compared. RESULTS: Administration of anti-TREM-1 mAb after PQ poisoning modeling significantly increased the NF-kappaB expression in lung tissue at 48 h, resulting in a large number of pro inflammatory cytokines releasing in the lung tissue and serum and lung pathology injury score increasing.Administration of LP17 after modeling significantly down .regulated the expressions of NF-kappaB and proinflammatory cytokines, while led to a slight increase of anti-inflammatory cytokines and a decline of lung pathology injury score. CONCLUSION: TREM-1 may involve in inflammatory response by promoting the generation of inflammatory factors via NF-kappaB pathway, thus lead to lung pathological changes. PMID- 26832697 TI - [Changes of CD(4)(+) Foxp3+ regulatory T cells and CD(4)(+)IL-17+T cells in acrolein exposure rats]. AB - OBJECTIVE: To evaluate the changes of CD(4)(+) IL-17+T (Th17) and CD(4)(+)Foxp3+regulatory T (Treg) cells in peripheral blood and bronchoalveolar lavage fluid (BALF) , and therefore to explore the role of Th17 and Treg in acrolein exposure airway inflammation in rats. METHODS: Forty male Wistar rats were randomly divided into 4 groups: a 2 wk acrolein exposure group, a 4 wk acrolein exposure group, a 2 wk control group and a 4 wk control group (n=10 each). Cells in BALF were collected and analyzed by absolute and differential cell counts.IL-17 and IL-6 levels in serum and BALF were tested by enzyme linked immunosorbent assay (ELISA). The proportion of CD(4)(+)IL-17+T and CD(4)(+) Foxp3+Treg in peripheral blood and BALF were determined by flow cytometry.The mRNA expressions of IL-17 and Foxp3 were measured by real-time PCR. Comparisons of the data between different groups were performed using one-way ANOVA, and SNK and Games-Howell test were used for comparison between 2 groups. RESULTS: Levels of IL-17 were remarkable increased in the 2 wk acrolein exposure group and the 4 wk acrolein exposure group in serum [(52.64 +/- 1.89) ng/L, (76.73 +/- 5.57) ng/L], and BALF [(79.07 +/- 5.67) ng/L, (96.61 +/- 6.44) ng/L] compared with the 2 wk control group [(40.05 +/- 3.12) ng/L, (56.75 +/- 4.37) ng/L] and the 4 wk control group [(38.75 +/- 3.23) ng/L, (53.27 +/- 4.48) ng/L], all P<0.01. IL-6 was increased in the 2 wk and the 4 wk acrolein exposure group [ (33.28 +/- 2.27) ng/L, (46.24 +/- 3.16) ng/L] compared with the 2 wk and the 4 wk control group [ (16.37 +/- 1.49) ng/L, (17.02 +/- 1.43) ng/L] in BALF.Ratio of Th17 was higher in the 2 wk and the 4 wk acrolein exposure groups in peripheral blood (1.82 +/- 0.18) %, (3.75 +/- 0.48) % and BALF [(7.23 +/- 0.27) %, (8.12 +/- 0.38) %] compared with the 2 wk [(0.96 +/- 0.07) %, (5.64 +/- 0.63) %] and the 4 wk control group [(1.01 +/- 0.08) %, (5.86 +/- 0.57) %]. Ratio of Treg in BALF was higher in the acrolein exposure groups [ (8.83 +/- 0.52) %, (12.05 +/- 0.74) %] compared with the control groups [(4.37 +/- 0.27) %, (5.01 +/- 0.37) %]. The level of IL-17 mRNA was increased in the 2 wk and the 4 wk acrolein exposure group in peripheral blood [(25.78 +/- 2.31), (34.69 +/- 2.01) ] and in BALF [(23.04 +/- 1.78), (34.56 +/- 3.12)] compared with the 2 wk [(11.04 +/- 2.53), (11.08 +/- 2.05)] and the 4 wk [(12.03 +/- 2.34), (12.69 +/- 2.69)] control groups. Foxp3 mRNA was increased in the acrolein exposure groups [ (26.37 +/- 3.24), (33.19 +/- 2.98)] (24.4 +/- 2.7), (30.3 +/- 2.7) compared with the control groups [(12.37 +/- 2.56), (13.12 +/- 3.08)]. Th17 in acrolein exposure groups was positively correlated with counts of total cells and macrophages (r=0.5126, 0.5437, all P<0.01). CONCLUSIONS: A changed expression of Th17 and Treg cells and an vary of inflammatory cytokines were evident in airway inflammation of acrolein exposed rats, suggesting that Treg was involved in the immunological regulation and Th17 was associated with the persistent inflammation in acrolein induced airway inflammation in rats. PMID- 26832698 TI - [Hemoperfusion alleviated paraquat-induced kidney inflammation injury of rabbit]. AB - OBJECTIVE: To investigate the effect of hemoperfusion on paraquat-Induced kidney inflammation injury of rabbit and the mechanism of it. METHODS: 60 male rabbits were randomly divided into 4 groups, the normal control group (n=6, the rabbits were given NS by gavage) , blank control group (n=18, he rabbits were given 2 hours hemoperfusion once within 1 hour after given NS by gavage), paraquat poisoning group (n=18, the rabbits were given 50 mg/kg 20% paraquat solution by gavage) , hemoperfusion treatment group (n=18, the rabbits were given 2 hours hemoperfusion once within 1 hour after 20% paraquat solution espoused). The last 3 groups were divided into 3 observation time groups (1, 3, 7 day), contained 6 rabbits each group. On days 1, 3, 7 all groups rabbits were anesthetized and sacrificed, and their kidney tissues collected. The levels of NF-kappaB mRNA by RT-PCR, and the expression of NF-kappaB protein was measured by Western blotting,The expression levels of TNF-alpha, IL-6, iNOS measured by chemical colorimetric method to to observe inflammatory injury. RESULTS: Compared with the normal control group rabbits, there were no changes in the TNF-alpha, IL-6, iNOS, NF-kappaB mRNA and protein of blank control group (P>0.05), while the expression of TNF-alpha, IL-6, NF-kappaB mRNA and protein in the kidney tissue of PQ group and were significantly increased (P<0.05). The pathological results of kidney tissues were no abnormalities onnormal control group and blank control group. CONCLUSION: HP significantly increase resistance to PQ-induced inflammation injury in the rabbit kidney and exert a protective effect on PQ-induced kidney injury. PMID- 26832699 TI - [Roles of epidermal growth factor receptor signaling pathway in silicon dioxide induced epithelial-mesenchymal transition in human pulmonary epithelial cells]. AB - OBJECTIVE: To investigate the effect of silicon dioxide (SiO2) on the expression of E-cadherin, alpha-smooth muscle actin (alpha-SMA), and transforming growth factor beta1(TGF-beta1) in human pulmonary epithelial cells (A549) with epithelial-mesenchymal transition (EMT), and to study the roles of epidermal growth factor receptor (EGFR) signaling pathway in SiO2-induced EMT in A549 cells in vitro. METHODS: Alveolar macrophages (AMs) were stimulated with 50 ug/ml SiO2for 3, 6, 12, 18, 24, or 36 h, and the supernatants were collected to measure the expression of TGF-beta1protein by ELISA. The AM supernatant in which TGF beta1reached the highest expression (T=18 h) was used as AM-conditioned supernatant. A549 cells were cultured in AM-conditioned supernatant and stimulated with indicated doses of SiO2(0, 50, 100, and 200 ug/ml) for 48 h. The cell morphological changes were observed using an inverted microscope. The cells were collected at different times, and the mRNA and protein expression levels of E-cadherin, alpha-SMA, and EGFR were measured by RT-PCR and immunocytofluorescence, respectively. RESULTS: After stimulation by SiO2, the expression level of TGF-beta1protein at each time point was significantly higher in the presence of AM supernatants than in the absence of AM supernatants (P<0.05). With the action time, the expression level of TGF-beta1protein increased at first and then decreased, and the highest level was reached at 18 h. After exposure to SiO2, A549 cells exhibited mesenchymal characteristics, such as a spindle shape, pseudopodia change, and fibroblast-like morphology, as observed by inverted microscope, especially in the 200 ug/ml group. With increased concentration of SiO2, the mRNA and protein expression of E-cadherin was down regulated gradually, especially in the 200 ug/ml group, whereas the mRNA and protein expression of alpha-SMA and EGFR was up-regulated gradually, especially in the 200 ug/m1 group. There were significant differences between the SiO2 treated groups (50, 100, and 200 ug/ml SiO2) and the control group (P<0.05). CONCLUSION: After being stimulated by SiO2in vitro, AMs have significantly increased expression level of TGF-beta1protein. The AM supernatant together with SiO2can induce the transition of pulmonary epithelial cells to mesenchymal cells, and its mechanism may be related to the EGFR signaling pathway. PMID- 26832700 TI - [Physiological index determination of oxygen supplementation for heavy worker of tibet plateau mine]. PMID- 26832701 TI - [Occupational noise-induced deafuess diaqnosis analysis in Jiangsu from 2006 to 2009]. AB - OBJECTIVE: In order to provide the evidence for taking the measures to prevent noise hazards, the condition sand influence factors of occupational noise deafness diagnosis in Jiangsu province from 2006 to 2013 were analyzed. METHODS: According to the 13 administrating personnel report of noise deafness diagnosed occupational disease prevention and control institutions in Jiangsu province from 2006 to 2013, the diagnosis of occupational noise deafness were retrospectively analyzed. RESULTS: By the end of December 31 2013, 297 cases of noise deafness were diagnosis occupational disease within this province. Occupational noise deafness has localized on the machinery industry, textile and light industry. Regional distribution mainly concentrated in Suzhou, Yangzhou, Nanjing, Nantong. 83.16% in 297 cases were mild noise deafness. CONCLUSION: The distribution of occupational noise deafness cases in Jiangsu province has specific charateristics. It is not balanced in different regions, and most of them are the mild noise deafness, male, length of service in more than 15 years, the onset age is 40~60 years old, According to characteristics of the occupational noise deafness cases in Jiangsu province, Specific occupational health service will help to reduce the occurrence of occupational noise deafness, and protect the worker's health effectively. PMID- 26832702 TI - [Analysis of Beijing suspected occupation disease reported and subsequent diagnosis during 2006 to 2013]. PMID- 26832703 TI - [Relationship between job burnout and cognitive function and influencing factors of job burn out among medical staff]. AB - OBJECTIVE: To explore the relationship between job burnout and cognitive function and the influencing factors of job burnout among medical staff. METHODS: Questionnaire survey was conducted for 197 medical workers in a grade-three general hospital in Beijing. Maslach Burnout Inventory-General Survey (MBI-GS) was carried out to assess the degree of job burnout among medical staff; Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to evaluate the overall cognitive function and cognitive situations of different dimensions. RESULTS: (1) There was a certain level of job burnout among medical staff, especially for the emotional exhaustion dimension (13.29 +/- 7.67). (2) High level job burnout group (81.08 +/- 12.34) scored lower on visual span than low level job burnout group (92.48 +/- 19.62), P<0.05. Overall, job burnout had a negative influence on the general cognitive function (P<0.05). (3) The results of regression analysis indicated that, inefficacy was negatively correlated with age (r=-0.162, P<0.05). Job burnout was positively correlated with level of education (r=0.234, P<0.05) as well as exercise frequency (r=0.320, P< 0.001), and emotional exhaustion was correlated with overtime work (r=0.135, P<0.05); Level of job burnout stayed higher among doctors and nurses, compared with administration staff in hospitals (t=2.966, P<0.05). CONCLUSION: Job burnout of medical staff was relatively in high level; influenced by age, education level, overtime work, exercise frequency and occupational type, job burnout affected the visual span and general cognitive function. PMID- 26832704 TI - [Effects on blood cell numbers and cytokines of dermal application rocket kerosene in mice]. AB - OBJECTIVE: To detect the number of cells and the level of IL-2, IL-4, IL-6, IL 10, TNF-alpha, IFN-gamma and IL-17 cytokines in the peripheral blood of mice exposed to rocket kerosene by skin. METHOD: ICR mice were randomly divided into the normal control group and RK experimental group (400 ul*1 group). RK undiluted fuel were applied directly to the dorsal skin of the mice. In control groups were treated with sesame oil (SO). the number of blood cells were detected by automatic blood cell counter and the level of IL-2, IL-4, IL-6, IL-10, TNF-alpha, IFN-gamma and IL-17 cytokines in serum were detected by using flow cytometry and BD CBA Flex set kit. RESULT: Compared with the normal group, WBC and LYM had a decreasing tendency 2 h and decreased significantly 6 h, 12 h and 1 d after RK exposure (P<0.05). They increased significantly 7 d after RK exposure (P<0.05). Compared with the normal group, the level of IL-6 increased significantly 2 h, 6 h, 12 h,1 d and 3 d (P<0.05). The level of TNF-alpha increased significantly 2h, 3d, 5d and 7d (P<0.05). The level of IL-10 increased significantly 2 h, 6 h, 3 d, 5 d and 7 d (P<0.05). The level of IFN-gamma increased significantly 6 h and 3 d (P< 0.05). The level of IL-17 significantly increased 3 d, 5 d and 7d (P<0.05). CONCLUSION: RK can change the number of immune cells, causing the immune cytokine changes in mice after RK cutaneous exposure. PMID- 26832705 TI - [Toxic effects of mixture of volatile organic compounds on mice testis related enzymes and hormones]. AB - OBJECTIVE: To evaluate the toxic effects of mixture of volatile organic compounds (VOCs) on Mice Testis related enzymes and hormones. METHODS: After determining the median lethal dose (LD50) of VOCs using the acute toxicity test, 40 male clean inbred Kunming mice were assigned to 1/8 LD50 VOCs exposure group, 1/4 LD50 VOCs exposure group, and 1/2 LD50 VOCs exposure group, as well as positive control group with cyclophosphamide (60 mg/kg) and negative control group with tea oil, with 8 mice in each group. The mice were intraperitoneally injected with respective agents for 5 days. The levels of testis testosterone, estradiol, follicle stimulating hormone, and luteinizing hormone were determined by ELISA. Meanwhile, the activity of testicular marked enzymes such as lactate dehydrogenase, gamma-glutamyl transpeptidase, acid phosphatase, and glucose-6 phosphate dehydrogenase were examined. RESULTS: Compared with the negative control group, the 1/8 LD50 exposure group had a significantly increased testis coefficient (P<0.05). Both the activity of testicular marked enzymes and the levels of testicular sex hormones in all exposure groups showed significant downward trends with increasing VOC doses compared with those in the negative control group (P<0.05). CONCLUSION: VOCs have obvious toxicity to mouse testis by changing the levels of testicular sex hormones and the activity of testicular marked enzymes. PMID- 26832706 TI - [Morphological assessment of sulfur mustard-induced acute lung injury in rats through different routes]. AB - OBJECTIVE: To establish an animal model of sulfur mustard (SM)-induced acute lung injury in rats through different routes and compare the morphological changes in lung tissue and cells. METHODS: One hundred and thirty-six male rats were selected and randomly divided into 5 groups, namely peritoneal cavity SM group (n=32), trachea SM group (n=32), peritoneal cavity propylene glycol group (n=32), trachea propylene glycol group (n=32), and normal control group (n=8). The rats in peritoneal cavity SM group were injected intraperitoneally with diluted SM (0.1 ml, 8 mg/kg), and the rats in trachea SM group were injected intratracheally with diluted SM (0.1 ml, 2 mg/kg). Once the rats were sacrificed at 6, 24, 48, and 72 h after SM treatment, morphological changes in lung tissue and cells were observed by light and electron microscopy. RESULTS: In the peritoneal cavity SM group, the epithelial cells of bronchioles maintained intact with increased exudate and bleeding in alveolar cavity and large areas of pulmonary consolidation under the light microscope. In the tracheal SM group, focal ulcer formed in the epithelial cells of bronchioles with increased exudate and bleeding in alveolar cavity, partial pulmonary consolidation, and compensatory emphysema in peripheral alveolar space under the light microscope. The alveolar interval areas were widened obviously in both groups in a time-dependent manner. Under the electron microscope, we observed local loss of cellular membrane in type I alveolar epithelium, broken or lost microvilli in cells of typeIIalveolar epithelium and fuzzy mitochondrial crista as well as the appearance of ribosome detached from rough endoplasmic reticulum in both two groups. Compared with those in the trachea SM group and the control group, the ratio of the alveolar septum average area to the visual field area in the peritoneal cavity SM group at 6, 24, 48, and 72 h was significantly higher (P<0.05). CONCLUSION: The lung tissue injury through the intraperitoneal route is more severe than that through the tracheal route, while focal ulceration of bronchioles epithelial cells appears in the case of tracheal route. The degree of injury increases over time in both groups, and the cellular damage is approximately the same in both groups. PMID- 26832707 TI - [Inhibitory effects of curcumin on inflammatory cytokines in rats with paraquat poisoning]. AB - OBJECTIVE: To explore the mechanism of paraquat (PQ) poisoning and to observe the changes in inflammatory cytokines in PQ-exposed rats treated in different ways. METHODS: Fifty 8-week-old clean male Wistar rats were randomly divided into high dose curcumin plus conventional treatment group, low-dose curcumin plus conventional treatment group, high-dose curcumin group, PQ poisoning group, and blank control group. On days 1, 3, 5, 7, 14, and 21 after PQ exposure, serum levels of transforming growth factor-beta1(TGF-beta1) , tumor necrosis factor alpha (TNF-alpha) , and interleukin-6 (IL-6) were measured. The pathological changes in lung tissue were evaluated by HE staining. RESULTS: Compared with the blank control group, the high-dose curcumin plus conventional treatment group, low-dose curcumin plus conventional treatment group, high-dose curcumin group, and PQ poisoning group had significantly increased serum levels of TGF-beta1, TNF alpha, and IL-6 (P<0.05) , and the three cytokines in each group reached peak levels on day 14 after exposure. Compared with the PQ poisoning group, the high dose curcumin group had significantly reduced serum levels of TGF-beta1, TNF alpha, and IL-6 (P<0.05). On day 21 after exposure, there were no significant differences in serum levels of TGF-beta1, TNF-alpha, and IL-6 between the high dose curcumin plus conventional treatment group and the low-dose curcumin plus conventional treatment group (P>0.05). The HE staining revealed alveolar inflammatory changes on days 1~7 and massive pulmonary fibrosis on days 14~21 in the high-dose curcumin plus conventional treatment group, low-dose curcumin plus conventional treatment group, high-dose curcumin group, and PQ poisoning group, but the above changes were milder in the high-dose curcumin group than in the PQ poisoning group. CONCLUSION: For rats with PQ poisoning, curcumin can significantly reduce inflammatory response and pathological changes in lung tissue and inhibit and delay the development and progression of body injury. PMID- 26832708 TI - [The prevention and therapeutics effect of sodium bicarbonate with gastric lavage, atomization inhalation and intravenous injection on the patients with paraquat poisoning and pulmonary fibrosis induced by paraquat poisoning]. AB - OBJECTIVE: To observe the prevention effects of patients with lung exudation and pulmonary fibrosis induced by paraquat poisoning in sodium bicarbonate (SB) with gastric lavage, atomization inhalation and intravenous injection. METHODS: To collect 38 patients with paraquat poisoning in hospital, after poison immediately with gastric lavage of 1.5% SB, and atomization inhalation of 5% SB 10~15 ml twice daily and intravenous injection of 5% SB twice a day, continuous application of 5~7 days. and the HRCT score and liver and kidney function was performed on patients with lung after treatment. And the extraction of 38 SB patients with previously untreated with SB for comparison. RESULTS: Lung HRCT average score in 72 h, 7 d, 30 d on patients with paraquat poisoning untreated with SB reached 2.87, 3.12, 2.13, HRCT display shows that the appearance of the wear glass shadow, grid shadow, honeycomb shadow, and other signs of fibrosis. Average HRCT reached 1.95, 2.20, 1.67 on patients treated with SB,signs of lung exudation and fibrosis was significantly reduced,compare two groups,there was statistically significance (P<0.01). And compared to the control group, activity of serum alanine aminotransferase (ALT) and aspartic acid transaminase (AST) decreased significantly in group of paraquat poisoning with triple application of SB, the level of serum urea nitrogen (BUN) and creatinine (Cr) significantly decreased, the difference is statistically significant (P<0.01). CONCLUSION: The triple application of SB can reduced the pulmonary fibrosis and effusion induced by paraquat poisoning,and protective effect on the function of liver and kidney is obvious, suggesting that the method for treatment of paraquat poisoning, prevention of paraquat lung and improve survival rate has the exact effect. PMID- 26832709 TI - [Clinical significance of dynamic changes in serum inflammatory cell factors after acute paraquat poisoning]. AB - OBJECTIVE: To investigate the clinical significance of dynamic changes in the serum inflammatory cell factors consisting of beta-endorphin (beta-EP) , endothelins (ET) , tumor necrosis factor (TNF) , and nitric oxide (NO) after acute paraquat poisoning (APP). METHODS: The 26 patients with APP (as observation group) were treated and the serum levels of plasma beta-EP, ET, TNF, and NO were measured simultaneously. The 20 healthy volunteers from relatives of the patients (as control group) were also included in the study and their serum levels of beta EP, ET, TNF, and NO were measured. RESULTS: In the 26 patients with APP, 10 were cured and 16 died. The serum levels of beta-EP, ET, NO, and TNF in the 10 cured patients increased significantly immediately after admission, reached the peak values on day 2, and then decreased gradually and returned to the normal ranges after day 9. The serum levels of beta-EP, ET, NO, and TNF in the 16 dead patients increased significantly on admission and kept rising in the course of treatment. The dead patients had significantly increased serum levels of beta-EP, ET, NO, and TNF compared with the cured patients (all P<0.01). CONCLUSION: Compared with those in cured patients with APP, the serum levels of beta-EP, ET, NO, and TNF in dead patients with APP are significantly higher, keep rising, and maintain at high levels, indicating a severe condition. PMID- 26832710 TI - [Analysis of prognostic value of initial serum paraquat concentration in patients with paraquat poisoning]. AB - OBJECTIVE: To investigate the prognostic values of initial serum paraquat (PQ) concentration and time lag after PQ ingestion in patients with PQ poisoning. METHODS: A retrospective analysis was performed on 189 patients who ingested PQ between 2.5 and 48 h before admission. The values of initial serum PQ concentration and time lag after PQ ingestion for the prognosis after poisoning were analyzed by the receiver operating characteristic (ROC) curve and multiple logistic regression analysis. RESULTS: The serum PQ concentration of non survivors was significantly higher than that of survivors (P<0.01) , and the time lag after PQ ingestion of non-survivors was significantly longer than that of survivors (P<0.01). The ROC curve analysis showed that the area under the ROC curve (AUC) showed no significant difference between initial serum PQ concentration and serum PQ concentration-time data when the time lag after PQ ingestion was between 2.5 and 48 h (z=0.563, P=0.574) ; the AUC showed a significant difference between initial serum PQ concentration and serum PQ concentration-time data when the time lag after PQ ingestion was between 2.5 and 6 h (z=2.199, P=0.034) and between 6 and 48 h (z=2.525, P=0.012). CONCLUSION: Initial serum PQ concentration has a better predictive power than serum PQ concentration-time data in evaluating the prognosis of patients when the time lag after PQ ingestion is within 6 h. However, serum PQ concentration-time data has a better predictive power than PQ concentration alone in evaluating the prognosis of patients when the time lag after PQ ingestion is between 6 and 48 h. PMID- 26832711 TI - [An accidents of diethyl phosphoryl chloride]. PMID- 26832712 TI - [Successful treatment of one case after acute paraquat intoxication complicated with pulmonary fibrosis, mediastinal emphysema and subcutaneous emphysema]. PMID- 26832713 TI - [Case of paraquat poisoning and diazepampoisoning inducing pulmonary embolism]. PMID- 26832714 TI - [A case of suspected acute toxic pulmonary edema caused by notrogen oxide]. PMID- 26832715 TI - [A case report about znfant poison caused by suckling poisoned milk secretool by his mother taking paraquat]. PMID- 26832716 TI - [A case report of acute imidacloprid poisoning]. PMID- 26832717 TI - [A case of severe phorate poisoning treatment]. PMID- 26832718 TI - [Advances in Immune Toxicity Research of Environmental Endocrine Disruptors]. PMID- 26832719 TI - [Digestive system injury caused by paraquat poisoning and treatment]. PMID- 26832720 TI - [Research advance in molecular mechanism of pulmonary fibrosis induced by paraquat poisoning]. PMID- 26832721 TI - The effects of haze on dew quality in the urban ecosystem of Changchun, Jilin Province, China. AB - Dew samples were collected during both normal weather and haze events (hazy days) to investigate the chemical characteristics of dew in Changchun, Jilin, China, from 2013 to 2015. The analysis included measures of the following parameters: pH, electrical conductivity (EC), total dissolved solid (TDS), and the concentration of PM2.5, PM10, major cations (NH4(+), Na(+), K(+), Ca(2+), and Mg(2+)), and major anions (F(-), Cl(-), SO4 (2-), and NO3(-)). The results demonstrated that dew water quality from hazy days was much lower quality than that on normal days with a lower mean pH during hazy days (5.75) when compared with that of normal days (6.56); that is, dew water was more acidic in stable atmospheric conditions. Both EC (542.71 MUs/cm) and TDS (271.36 mg/L) of dew on hazy days were higher than that on normal days. The mean concentration of particulate matter <2.5 and 2.5-10 MUm in diameter (PM2.5 and PM10, respectively) was 21.69 and 51.56 mg/L on normal days and were over 2.48 and 1.79 times higher on hazy days, respectively; that is, dew removed more fine particles on hazy days. On hazy days, the concentrations of water-soluble ions were 3.01-9.32 times higher than levels on normal days. The concentrations of secondary species and K(+) on hazy days were much higher than those of other ions. The results indicated dew mainly removed aerosols from automobile exhaust, and industrial waste gas emissions, while to a lesser extent dew did scavenge some water-soluble crustal ions. PMID- 26832722 TI - Ecological risk assessment of heavy metals in soils surrounding oil waste disposal areas. AB - More attention is being devoted to heavy metal pollution because heavy metals can concentrate in higher animals through the food chain, harm human health and threaten the stability of the ecological environment. In this study, the effects of heavy metals (Cu, Cr, Zn, Pb, Cd, Ni and Hg) emanating from oil waste disposal on surrounding soil in Jilin Province, China, were investigated. A potential ecological risk index was used to evaluate the damage of heavy metals and concluded that the degree of potential ecological damage of heavy metals can be ranked as follows: Hg > Cd > Pb > Cu > Ni > Cr > Zn. The average value of the potential ecological harm index (Ri) is 71.93, thereby indicating light pollution. In addition, this study researched the spatial distribution of soil heavy metals by means of ArcGIS (geographic information system) spatial analysis software. The results showed that the potential ecological risk index (R) of the large value was close to the distance from the oil waste disposal area; it is relatively between the degree of heavy metals in soil and the distance from the waste disposal area. PMID- 26832723 TI - Analysis of field-scale spatial correlations and variations of soil nutrients using geostatistics. AB - Spatial correlations and soil nutrient variations are important for soil nutrient management. They help to reduce the negative impacts of agricultural nonpoint source pollution. Based on the sampled available nitrogen (AN), available phosphorus (AP), and available potassium (AK), soil nutrient data from 2010, the spatial correlation, was analyzed, and the probabilities of the nutrient's abundance or deficiency were discussed. This paper presents a statistical approach to spatial analysis, the spatial correlation analysis (SCA), which was originally developed for describing heterogeneity in the presence of correlated variation and based on ordinary kriging (OK) results. Indicator kriging (IK) was used to assess the susceptibility of excess of soil nutrients based on crop needs. The kriged results showed there was a distinct spatial variability in the concentration of all three soil nutrients. High concentrations of these three soil nutrients were found near Anzhou. As the distance from the center of town increased, the concentration of the soil nutrients gradually decreased. Spatially, the relationship between AN and AP was negative, and the relationship between AP and AK was not clear. The IK results showed that there were few areas with a risk of AN and AP overabundance. However, almost the entire study region was at risk of AK overabundance. Based on the soil nutrient distribution results, it is clear that the spatial variability of the soil nutrients differed throughout the study region. This spatial soil nutrient variability might be caused by different fertilizer types and different fertilizing practices. PMID- 26832724 TI - Bacterial pollution, activity and heterotrophic diversity of the northern part of the Aegean Sea, Turkey. AB - Isolation and characterization studies of marine heterotrophic bacteria are important to describe and understand eco-metobolism of the marine environments. In this study, diversity and community structures of the culturable heterotrophic bacteria, metabollicaly active bacteria and bacterial pollution in the coastal and offshore areas of Gokceada Island, in the Northern Aegean Sea, Turkey were investigated from March 2012 to November 2013. The primary hydrographic parameters were recorded in situ. The frequency of the metabolically active bacteria was determined by using a modified staining technique. The indicator bacteria were determined by using membrane filtration technique; 126 bacteria isolates, 24 of them first records for this region, were identified using an automated micro-identification system, VITEK2 Compact30. The results showed that detected bacterial community profiles were significantly different when compared with previous studies conducted in polluted marine areas of Turkey. High frequency of faecal bacteria detected at station 2 indicated that increasing human activities and terrestrial pollution sources are shaping factors for possible risks, regarding recreational uses of this region, in the summer seasons. PMID- 26832725 TI - Body burdens of heavy metals in Lake Michigan wetland turtles. AB - Tissue heavy metal concentrations in painted (Chrysemys picta) and snapping (Chelydra serpentina) turtles from Lake Michigan coastal wetlands were analyzed to determine (1) whether turtles accumulated heavy metals, (2) if tissue metal concentrations were related to environmental metal concentrations, and (3) the potential for non-lethal sampling techniques to be used for monitoring heavy metal body burdens in freshwater turtles. Muscle, liver, shell, and claw samples were collected from painted and snapping turtles and analyzed for cadmium, chromium, copper, iron, lead, magnesium, manganese, and zinc. Turtle tissues had measurable quantities of all eight metals analyzed. Statistically significant correlations between tissue metal concentrations and sediment metal concentrations were found for a subset of metals. Metals were generally found in higher concentrations in the larger snapping turtles than in painted turtles. In addition, non-lethal samples of shell and claw were found to be possible alternatives to lethal liver and muscle samples for some metals. Human consumption of snapping turtles presents potential health risks if turtles are harvested from contaminated areas. Overall, our results suggest that turtles could be a valuable component of contaminant monitoring programs for wetland ecosystems. PMID- 26832727 TI - Chronic and Acute Relational Risk Factors for Dating Aggression in Adolescence and Young Adulthood. AB - Dating aggression is a prevalent and costly public health concern. Using a relational risk framework, this study examined acute and chronic relational risk factors (negative interactions, jealousy, support, and relationship satisfaction) and their effects on physical and psychological dating aggression. The study also examined the interaction between chronic and acute risk, allowing us to assess how changes in acute risk have differing effects depending on whether the individual is typically at higher chronic risk. A sample of 200 youth (100 female) completed seven waves of data, which spanned 9 years from middle adolescence to young adulthood (M age at Wave 1 = 15.83). Using hierarchical linear modeling, analyses revealed both acute (within-person) and chronic (between-person) levels in jealousy, negative interactions, and relationship satisfaction, were associated with physical and psychological dating aggression. Significant interactions between chronic and acute risk emerged in predicting physical aggression for negative interactions, jealousy, and relationship satisfaction such that those with higher levels of chronic risk are more vulnerable to increases in acute risk. These interactions between chronic and acute risk indicate that risk is not static, and dating aggression is particularly likely to occur at certain times for youth at high risk for dating aggression. Such periods of increased risk may provide opportunities for interventions to be particularly effective in preventing dating aggression or its consequences. Taken together, these findings provide support for the role of relational risk factors for dating aggression. They also underscore the importance of considering risk dynamically. PMID- 26832726 TI - The Relationship Between Family Functioning and Adolescent Depressive Symptoms: The Role of Emotional Clarity. AB - Emotion regulation has been implicated in the etiology of depression. A first step in adaptive emotion regulation involves emotional clarity, the ability to recognize and differentiate one's emotional experience. As family members are critical in facilitating emotional understanding and communication, we examined the impact of family functioning on adolescent emotional clarity and depressive symptoms. We followed 364 adolescents (ages 14-17; 52.5% female; 51.4 % Caucasian, 48.6% African American) and their mothers over 2 years (3 time points) and assessed emotional clarity, depressive symptoms, and adolescents' and mothers' reports of family functioning. Emotional clarity mediated the relationship between adolescents' reports of family functioning and depressive symptoms at all time points cross-sectionally, and according to mothers' reports of family functioning at Time 1 only. There was no evidence of longitudinal mediation for adolescents' or mothers' reports of family functioning. Thus, family functioning, emotional clarity, and depressive symptoms are strongly related constructs during various time points in adolescence, which has important implications for intervention, especially within the family unit. PMID- 26832728 TI - Genotyping of single nucleotide polymorphisms related to attention-deficit hyperactivity disorder. AB - Pharmacological treatment of several diseases, such as attention-deficit hyperactivity disorder (ADHD), presents marked variability in efficiency and its adverse effects. The genotyping of specific single nucleotide polymorphisms (SNPs) can support the prediction of responses to drugs and the genetic risk of presenting comorbidities associated with ADHD. This study presents two rapid and affordable microarray-based strategies to discriminate three clinically important SNPs in genes ADRA2A, SL6CA2, and OPRM1 (rs1800544, rs5569, and rs1799971, respectively). These approaches are allele-specific oligonucleotide hybridization (ASO) and a combination of allele-specific amplification (ASA) and solid-phase hybridization. Buccal swab and blood samples taken from ADHD patients and controls were analyzed by ASO, ASA, and a gold-reference method. The results indicated that ASA is superior in genotyping capability and analytical performance. PMID- 26832729 TI - Quantification of low molecular weight selenium metabolites in human plasma after treatment with selenite in pharmacological doses by LC-ICP-MS. AB - The paper presents an analytical method for quantification of low molecular weight (LMW) selenium compounds in human plasma based on liquid chromatography inductively coupled plasma mass spectrometry (LC-ICP-MS) and post column isotope dilution-based quantification. Prior to analysis, samples were ultrafiltrated using a cut-off value of 3000 Da. The method was validated in aqueous solution as well as plasma using standards of selenomethionine (SeMet), Se methylselenocysteine (MeSeCys), selenite, and the selenosugar Se-methylseleno-N acetylgalactosamine (SeGal) for linearity, precision, recoveries, and limits of detection and quantitation with satisfactory results. The method was applied for analysis of a set of plasma samples from cancer patients receiving selenite treatment in a clinical trial. Three LMW selenium compounds were observed. The main compounds, SeGal and selenite were tentatively identified by retention time matching with standards in different chromatographic systems, while the third minor compound was not identified. The identity of the selenosugar was verified by ESI-MS-MS product ion scanning, while selenite was identified indirectly as the glutathione (GSH) reaction product, GS-Se-SG. PMID- 26832730 TI - Biomarkers for the identification of precursor polyps of colorectal serrated adenocarcinomas. AB - BACKGROUND: In contrast to conventional colorectal carcinomas (CCs), which develop through a so-called chromosome instability or suppressor phenotype pathway, the sequence of events leading from precursor polyps/adenomas to serrated adenocarcinomas (SACs), which are more aggressive and exhibit a poorer survival than CCs, is as yet not clearly defined. Here, we aimed at detecting protein and DNA biomarkers for SAC in a series of primary colorectal polyps. METHODS: In total 303 colorectal polyps were included: 121 serrated polyps (33 hyperplastic polyps, 37 sessile serrated adenomas (SSA), 51 traditional serrated adenomas (TSA)), 143 conventional polyps (72 tubular polyps, 34 tubulovillous polyps, 37 villious adenomas), and 39 bi-phenotypic serrated-conventional polyps. The protein biomarkers tested were deduced from previously published SAC and CC expression profiling studies. A representative subset of 106 polyps was selected for DNA biomarker analyses, i.e., proto-oncogene mutation and microsatellite instability (MSI) status. In order to confer proper weight to each biomarker, a multivariate logistic regression model was employed. RESULTS: We found that serrated and conventional polyps differed in most of the SAC biomarkers tested. Of these biomarkers, FSCN1 showed the largest difference in expression (p = 0.0001). Despite sharing a serrated morphology, we found that SSAs and TSAs differed considerably with respect to anatomical location, expression of EPHB2 and PTCH1, presence of the V600E BRAF mutation and MSI status. Logistic regression analysis revealed that SSA was the polyp type that shared most biomarkers with SAC. CONCLUSION: Based on the shared presence of protein and molecular biomarkers, especially FSCN1 expression, SSA may serve as a precursor lesion of SAC. Biomarker assessment may help in discerning colorectal carcinogenic routes with distinct prognostic implications. PMID- 26832732 TI - [Confocal microscopy for the diagnostics of fungal keratitis]. AB - Fungal keratitis is a rare but very serious eye disease in industrial nations with a frequency of 1-5 % of all forms of keratitis from microbial causes. We present two patients with keratitis of primary unknown cause. Using confocal microscopy fungal filaments could be identified that partially showed a parallel configuration (like "railway tracks"). Thus, the correct diagnosis can often be made and suitable therapy can be non-invasively initiated even before the results of in vitro cultivation (fungal culture), polymerase chain reaction (PCR) and histological investigations are available. PMID- 26832731 TI - Copy number gain of PIK3CA and MET is associated with poor prognosis in head and neck squamous cell carcinoma. AB - The incidence of head and neck squamous cell carcinomas is still growing, and the long-term prognosis of advanced disease remains poor. Only a fraction of head and neck cancers are sensitive to the EGFR-inhibitor cetuximab, which is the only registered targeted therapy available today. In several cancers, gene copy number alterations of MET and PIK3CA have been found to be prognostic and predictive for therapy response. The aim of this study was to systematically analyze in head and neck cancers the pathological characteristics and prognostic significance of copy number changes of MET and PIK3CA genes. MET and PIK3CA copy numbers were analyzed by fluorescence in situ hybridization in tumor samples of 152 patients. Expression of EGFR, p16, and Ki67 was studied by immunohistochemistry. High polysomy of PIK3CA (chromosome 3) was found in 20 % of cases and amplification in 4.5 %. Regarding MET, 35 % of cases showed low or high polysomy of the gene (chromosome 7), while no intra-chromosomal amplification of MET was detected. PIK3CA copy number gain (high polysomy or amplification) was significantly associated with shorter disease-specific survival, larger tumor volume, and lower p16 expression. MET copy number gain (low or high polysomy) in tumors was significantly associated with shorter disease-specific survival and lower level of EGFR. PIK3CA and MET may play an important role in oncogenesis of certain specific subtypes of head and neck cancer. There is an urgent need for the development of novel targeted therapies against these tumors associated with poor prognosis. PMID- 26832733 TI - [Update: Deep anterior lamellar keratoplasty (DALK) for keratoconus. When, how and why]. AB - BACKGROUND: The treatment of keratoconus has been significantly expanded in recent years. In addition to the previous options for correction by fitting hard contact lenses and penetrating keratoplasty (PK), corneal cross-linking and lamellar transplantation techniques have been added. OBJECTIVE: The aim of this review article is to highlight currently available options for minimization of complications and standardization of deep anterior lamellar keratoplasty (DALK) for keratoconus. MATERIAL AND METHODS: This article summarizes our own data and gives a review of the literature in PubMed. RESULTS: Performing DALK can provide keratoconus patients with corneal grafts with considerably longer graft survival and a reduced risk of complications. CONCLUSION: The DALK procedure provides numerous advantages over PK, especially the reduced intraoperative opening of the eye, which thus reduces the risk of serious intraoperative complications. A further benefit is the complete absence of postoperative endothelial immune reactions as the recipient's endothelium remains untouched. The absence of endothelial immune reactions is especially advantageous for young patients with keratoconus and patients with an increased risk of graft rejection, e.g. in atopic dermatitis; however, there are also typical complications of DALK that do not occur during PK. The outlined strategies for standardization of DALK and avoidance of intraoperative and postoperative complications should make DALK safer and more reproducible and lead to possible establishment as a standard procedure in keratokonus. PMID- 26832734 TI - Determination of Bile Acids in Piglet Bile by Solid Phase Extraction and Liquid Chromatography-Electrospray Tandem Mass Spectrometry. AB - An LC/MS/MS-based method was developed for the determination of individual bile acids (BA) and their conjugates in porcine bile samples. The C18-based solid phase extraction (SPE) procedure was optimized so that all 19 target BA and their glycine and taurine conjugates were collected with high recoveries for standards (89.1-100.2%). Following this, all 19 compounds were separated and quantified in a single 12 min chromatographic run. The method was validated in terms of linearity, sensitivity, accuracy, precision, and recovery. An LOD in the low ppb range with measured precisions in the range of 0.5-9.3% was achieved. The recoveries for all of the 19 analytes in bile samples were all >80%. The validated method was successfully applied to the profiling of BA and their conjugates in the bile from piglets treated with exogenous glucagon-like peptide 2 (GLP-2) in a preclinical model of neonatal parenteral nutrition-associated liver disease (PNALD). The method developed is rapid and could be easily implemented for routine analysis of BA and their conjugates in other biofluids or tissues. PMID- 26832735 TI - Kinetics of Bis-Allylic Hydroperoxide Synthesis in the Iron-Containing Lipoxygenase 2 from Cyanothece and the Effects of Manganese Substitution. AB - Lipoxygenases (LOX) catalyze the regio- and stereospecific insertion of dioxygen into polyunsaturated fatty acids. While the catalytic metal of LOX is typically a non-heme iron, some fungal LOX contain manganese as catalytic metal (MnLOX). In general, LOX insert dioxygen at C9 or C13 of linoleic acid leading to the formation of conjugated hydroperoxides. MnLOX (EC 1.13.11.45), however, catalyze the oxygen insertion also at C11, resulting in bis-allylic hydroperoxides. Interestingly, the iron-containing CspLOX2 (EC 1.13.11.B6) from Cyanothece PCC8801 also produces bis-allylic hydroperoxides. What role the catalytic metal plays and how this unusual reaction is catalyzed by either MnLOX or CspLOX2 is not understood. Our findings suggest that only iron is the catalytically active metal in CspLOX2. The enzyme loses its catalytic activity almost completely when iron is substituted with manganese, suggesting that the catalytic metal is not interchangeable. Using kinetic and spectroscopic approaches, we further found that first a mixture of bis-allylic and conjugated hydroperoxy products is formed. This is followed by the isomerization of the bis-allylic product to conjugated products at a slower rate. These results suggest that MnLOX and CspLOX2 share a very similar reaction mechanism and that LOX with a Fe or Mn cofactor have the potential to form bis-allylic products. Therefore, steric factors are probably responsible for this unusual specificity. As CspLOX2 is the LOX with the highest proportion of the bis-allylic product known so far, it will be an ideal candidate for further structural analysis to understand the molecular basis of the formation of bis-allylic hydroperoxides. PMID- 26832736 TI - Effectiveness and micro-costing of the KiVa school-based bullying prevention programme in Wales: study protocol for a pragmatic definitive parallel group cluster randomised controlled trial. AB - BACKGROUND: Bullying refers to verbal, physical or psychological aggression repeated over time that is intended to cause harm or distress to the victims who are unable to defend themselves. It is a key public health priority owing to its widespread prevalence in schools and harmful short- and long-term effects on victims' well-being. There is a need to strengthen the evidence base by testing innovative approaches to preventing bullying. KiVa is a school-based bullying prevention programme with universal and indicated elements and an emphasis on changing bystander behaviour. It achieved promising results in a large trial in Finland, and now requires testing in other countries. This paper describes the protocol for a cluster randomised controlled trial (RCT) of KiVa in Wales. METHODS/DESIGN: The study uses a two-arm waitlist control pragmatic definitive parallel group cluster RCT design with an embedded process evaluation and calculation of unit cost. Participating schools will be randomised a using a 1:1 ratio to KiVa plus usual provision (intervention group) or usual provision only (control group). The trial has one primary outcome, child self-reported victimisation from bullying, dichotomised as 'victimised' (bullied at least twice a month in the last couple of months) versus 'not victimised'. Secondary outcomes are: bullying perpetration; aspects of child social and emotional well-being (including emotional problems, conduct, peer relations, prosocial behaviour); and school attendance. Follow-up is at 12 months post-baseline. Implementation fidelity is measured through teacher-completed lesson records and independent school-wide observation. A micro-costing analysis will determine the costs of implementing KiVa, including recurrent and non-recurrent unit costs. Factors related to the scalability of the programme will be examined in interviews with head teachers and focus groups with key stakeholders in the implementation of school-based bullying interventions. DISCUSSION: The results from this trial will provide evidence on whether the KiVa programme is transportable from Finland to Wales in terms of effectiveness and implementation. It will provide information about the costs of delivery and generate insights into factors related to the scalability of the programme. TRIAL REGISTRATION: Current Controlled Trials ISRCTN23999021 Date 10-6-13. PMID- 26832737 TI - Predictors of dropout from care among HIV-infected patients initiating antiretroviral therapy at a public sector HIV treatment clinic in sub-Saharan Africa. AB - BACKGROUND: In sub-Saharan Africa (SSA), antiretroviral therapy (ART) can prolong life for HIV-infected patients. However, patients initiating ART, especially in routine treatment programs, commonly dropout from care either due to death or loss to follow-up. METHODS: In a cohort of HIV-infected patients initiating ART at a public sector clinic in Uganda, we assessed predictors of dropout from care (a composite outcome combining death and loss to follow-up). From a large set of socio-demographic, clinical, and laboratory variables routinely collected at ART initiation, we selected those predicting dropout at P <0.1 in unadjusted analyses for inclusion into a multivariable proportional hazards regression model. We then used a stepwise backward selection procedure to identify variables which independently predicted dropout at P <0.05. RESULTS: Data from 5,057 patients were analyzed. The median age was 33 years (IQR 28 to 40) and 27.4% had CD4+ T cell counts <100 cells/MUL at ART initiation. The median duration of follow-up was 24 months (IQR = 14 to 42, maximum follow-up = 64 months). Overall dropout was 26.9% (established cumulative mortality = 2.3%, loss to follow-up = 24.6%), 5.6% were transferred to other service providers, and 67.5% were retained in care. A diagnosis of Kaposi's sarcoma (hazard ratio (HR) = 3.3, 95% CI 2.5 to 4.5); HIV-associated dementia (HR = 2.6, 95% CI 1.5 to 4.6); history of cryptococcosis (HR = 2.2, 95% CI 1.4 to 3.3); and reduced hemoglobin concentration (<11 g/dl versus >=13.8 g/dl (HR = 1.9, 95% CI 1.6 to 2.2) were strong predictors of dropout. Other independent predictors of dropout were: year of ART initiation; weight loss >=10%; reduced total lymphocyte count; chronic diarrhea; male sex; young age (<=28 years); and marital status. CONCLUSIONS: Among HIV-infected patients initiating ART at a public sector clinic in SSA, biological factors that usually predict death were especially predictive of dropout. As most of the dropouts were lost to follow-up, this observation suggests that many losses to follow-up may have died. Future studies are needed to identify appropriate interventions that may improve both individual-level patient outcomes and outcome ascertainment among HIV-infected ART initiators in this setting. PMID- 26832738 TI - Product Attributes and Purchasing Behaviour: How Parents' Food Choices Can Act on Their Children's BMI? Empirical Evidence from a Case Study. AB - BACKGROUND: Given the epidemic proportions and economic costs associated with nutrition related diseases in Western countries, an empirical study was carried out between September and December 2014 in Campania, the Italian region with the highest prevalence of obese children. METHODS: The survey was conducted in a secondary school and involved 145 children, aged 11 to 14, and their parents, with the ultimate aim of studying the relationship between the behaviour of parents regarding the use of nutrition labels, the attention to product quality and the body weight of their children. RESULTS: The results from our study showed that unhealthy diet concerned stems from the misguided food choices of their parents, who are responsible for their children's dietary habits, lifestyle and body weight. CONCLUSION: In order to incentivise adults and young people to change their food choices and eating behaviour in favour of healthy and sustainable lifestyles, some useful measures could involve the improvement of political marketing and advertising, labelling clarity and better information and awareness campaigns to do sport and eat healthily. Finally some recent patents related to healthy reformulated food products and communication strategies, with specific regard to healthy eating, have been reviewed. PMID- 26832739 TI - The Efficacy of Perindopril/Amlodipine in Reaching Blood Pressure Targets: Results of the CONTROL Study. AB - BACKGROUND: Inadequate blood pressure (BP) control remains a serious concern worldwide. Recent evidence suggests that the combination of a calcium channel blocker (CCB) with an angiotensin-converting enzyme inhibitor (ACEi) in patients with essential hypertension provides effective BP control with decreased adverse cardiac and renal events. OBJECTIVES: This study was designed to quantitatively evaluate the efficacy and tolerability of a fixed dose combination of perindopril and amlodipine in the Kingdom of Saudi Arabia on a population of patients with essential hypertension, as well as to identify the predictors of BP control in this population. METHODS: This was an observational, multicenter, open-label cohort study of patients with essential hypertension with or without diabetes mellitus, treated with a fixed dose combination of perindopril and amlodipine. Patients were followed up in four-week intervals for a total of 12 weeks. They were initially started on the lowest dose of the ACEi/CCB combination and up titrated at each follow-up according to their response to treatment. The primary end-point of the study was the percentage of patients with controlled BP at study termination (week 12). RESULTS: A total of 1996 patients completed the study. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) control was observed in 93.3% of patients at week 12. As for the predictors of BP control, it was found that female gender was associated with more BP control [odds ratio (OR) = 1.76, 95% CI: 1.14-2.70, p value = 0.01], whereas older age was associated with less BP control (OR = 0.98, 95% CI: 0.96-1.00, p value = 0.02). Similarly, having type I and type II diabetes mellitus was also associated with less BP control (OR = 0.19, 95% CI: 0.08-0.45, p < 0.0001 and OR = 0.33, 95% CI: 0.22-0.48, p < 0.0001, respectively). In a qualitative assessment, both investigators and patients perceived efficacy and tolerability of perindopril/amlodipine to be excellent. CONCLUSION: We found that a fixed combination of perindopril/amlodipine is effective in controlling BP in patients with essential hypertension, with older age, male gender, and diabetes mellitus being independent risk factors for less BP control. PMID- 26832740 TI - Treatment of lumbosacral spinal tuberculosis by one-stage anterior debridement and fusion combined with dual screw-rod anterior instrumentation underneath the iliac vessel. AB - BACKGROUND: There has been no consensus regarding what is the optimal means of treating lumbosacral segment tuberculosis. The aim of this study was to evaluate the clinical outcomes of our newly developed one-stage anterior debridement and fusion combined with dual screw-rod construct anterior instrument underneath the iliac vessels for lumbosacral spinal tuberculosis. METHODS: We retrospectively reviewed 22 patients with lumbosacral spinal tuberculosis who underwent one-stage anterior debridement and fusion combined with dual screw-rod anterior instrument underneath the iliac vessels between January 2004 and June 2013. We assessed the visual analogue scale (VAS), erythrocyte sedimentation rates (ESR), neurological performance, kyphotic angles, fusion rates, and computed tomographic angiography (CTA) before and after surgery. RESULTS: All patients were followed-up for a mean of 46.59 months. There were no instances of spinal tuberculosis recurrence. The mean VAS scores and ESR decreased significantly from the preoperative levels both postoperatively and at the final follow-up (all P <0.001). The mean kyphotic angle significantly increased from the mean preoperative angle both postoperatively and at the final follow-up (both P <0.001). All patients had bone fusion at a mean of five months after surgery. No postoperative vascular complications were observed. CONCLUSIONS: Our findings suggest that anterior radical debridement, fusion combined with dual screw-rod anterior instrument underneath the iliac vessels can be an effective and safe treatment option for lumbosacral segment tuberculosis. PMID- 26832742 TI - Erratum to: First detection, clinical presentation and phylogenetic characterization of Porcine epidemic diarrhea virus in Austria. PMID- 26832741 TI - Low oxygen tension reverses antineoplastic effect of iron chelator deferasirox in human glioblastoma cells. AB - BACKGROUND: Overcoming resistance to treatment is an essential issue in many cancers including glioblastoma (GBM), the deadliest primary tumor of the central nervous system. As dependence on iron is a key feature of tumor cells, using chelators to reduce iron represents an opportunity to improve conventional GBM therapies. The aim of the present study was, therefore, to investigate the cytostatic and cytotoxic impact of the new iron chelator deferasirox (DFX) on human GBM cells in well-defined clinical situations represented by radiation therapy and mild-hypoxia. RESULTS: Under experimental normoxic condition (21% O2), deferasirox (DFX) used at 10 MUM for 3 days reduced proliferation, led cell cycle arrest in S and G2-M phases and induced cytotoxicity and apoptosis in U251 and U87 GBM cells. The abolition of the antineoplastic DFX effects when cells were co-treated with ferric ammonium sulfate supports the hypothesis that its effects result from its ability to chelate iron. As radiotherapy is the main treatment for GBM, the combination of DFX and X-ray beam irradiation was also investigated. Irradiation at a dose of 16 Gy repressed proliferation, cytotoxicity and apoptosis, but only in U251 cells, while no synergy with DFX was observed in either cell line. Importantly, when the same experiment was conducted in mild-hypoxic conditions (3% O2), the antiproliferative and cytotoxic effects of DFX were abolished, and its ability to deplete iron was also impaired. CONCLUSIONS: Taken together, these in vitro results could raise the question of the benefit of using iron chelators in their native forms under the hypoxic conditions often encountered in solid tumors such as GBM. Developing new chemistry or a new drug delivery system that would keep DFX active in hypoxic cells may be the next step toward their application. PMID- 26832744 TI - 2013 HIPAA Changes Provide Opportunities and Challenges for Researchers: Perspectives from a Cancer Center. AB - In 2013, the U.S. Department of Health and Human Services modified the Health Insurance Portability and Accountability Act Privacy Rule to "strengthen privacy and security protections" while "improving workability and effectiveness to increase flexibility for and decrease burden on regulated entities." In this article, we attempt to translate these generalized goals into the real-world implications of these changes. Under the new rules, researchers can obtain participants' permission to use their protected health information for more research activities with a single, upfront authorization (thereby reducing paperwork for participants, researchers, and institutional review boards) while providing potential participants with more information upon which to base their decisions about participation. The combined authorizations can be used in clinical trials and their optional substudies and in stand-alone biospecimen banking research that includes authorization to permit future research use. We also suggest best practices for taking advantage of the flexibility offered by the new rules while maintaining strong privacy protections for human subjects. PMID- 26832745 TI - NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models. AB - PURPOSE: Aldesleukin, recombinant human IL2, is an effective immunotherapy for metastatic melanoma and renal cancer, with durable responses in approximately 10% of patients; however, severe side effects limit maximal dosing and thus the number of patients able to receive treatment and potential cure. NKTR-214 is a prodrug of conjugated IL2, retaining the same amino acid sequence as aldesleukin. The IL2 core is conjugated to 6 releasable polyethylene glycol (PEG) chains. In vivo, the PEG chains slowly release to generate active IL2 conjugates. EXPERIMENTAL DESIGN: We evaluated the bioactivity and receptor binding of NKTR 214 and its active IL2 conjugates in vitro; the tumor immunology, tumor pharmacokinetics, and efficacy of NKTR-214 as a single agent and in combination with anti-CTLA-4 antibody in murine tumor models. Tolerability was evaluated in non-human primates. RESULTS: In a murine melanoma tumor model, the ratio of tumor killing CD8(+) T cells to Foxp3(+) regulatory T cells was greater than 400 for NKTR-214 compared with 18 for aldesleukin, supporting preferential activation of the IL2 receptor beta over IL2 receptor alpha, due to the location of PEG molecules. NKTR-214 provides a 500-fold greater exposure of the tumor to conjugated IL2 compared with aldesleukin. NKTR-214 showed efficacy as a single agent and provided durable immunity that was resistant to tumor rechallenge in combination with anti-CTLA-4 antibody. NKTR-214 was well tolerated in non-human primates. CONCLUSIONS: These data support further evaluation of NKTR-214 in humans for a variety of tumor types, adding to the repertoire of potent and potentially curative cancer immunotherapies. PMID- 26832746 TI - Safety and acceptability of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 in Bangladeshi infants: a phase I randomized clinical trial. AB - BACKGROUND: Probiotics have rarely been studied in young healthy infants from low income countries. This phase I study investigated the safety and acceptability of two probiotics in Bangladesh. METHODS: Healthy infants aged four to twelve weeks from urban slums in Bangladesh were randomized to one of three different intervention dosing arms (daily, weekly, biweekly - once every two weeks) of Lactobacillus reuteri DSM 17938 and Bifidobacterium longum subspecies infantis 35624 over one month or to a fourth arm that received no probiotics. All subjects were followed for two additional months. Reported gastrointestinal and respiratory symptoms as well as breastfeeding rates, hospitalizations, differential withdrawals, and caretakers' perception of probiotic use were compared among arms. RESULTS: In total, 160 infants were randomized (40 to each arm) with 137 (Daily n = 35, Weekly n = 35, Biweekly n = 35, Control n = 32) followed up for a median of twelve weeks; 113 completed the study. Illness and breastfeeding rates were similar across all arms. Ten hospitalizations unrelated to probiotic use occurred. Forty eight percent of the caretakers of infants in intervention arms believed that probiotics improved their baby's health. CONCLUSIONS: These two commonly used probiotics appeared safe and well-accepted by Bangladeshi families. TRIAL REGISTRATION: ClinicalTrials.gov NCT01899378 . Registered July 10, 2013. PMID- 26832747 TI - Use of Diuretics is not associated with mortality in patients admitted to the emergency department: results from a cross-sectional study. AB - BACKGROUND: Patients with diuretic therapy are at risk for drug-induced adverse reactions. It is unknown if presence of diuretic therapy at hospital emergency room admission is associated with mortality. METHODS: In this cross sectional analysis, all emergency room patients 2010 and 2011 at the Inselspital Bern, Switzerland were included. A multivariable logistic regression model was performed to assess the association between pre-existing diuretic medication and 28 day mortality. RESULTS: Twenty-two thousand two hundred thirty-nine subjects were included in the analysis. A total of 8.5%, 2.5%, and 0.4% of patients used one, two, or three or more diuretics. In univariate analysis spironolactone, torasemide and chlortalidone use were associated with 28 day mortality (all p < 0.05). In a multivariate cox regression model no association with mortality was detectable (p > 0.05). No difference existed between patients with or without diuretic therapy (P > 0.05). Age and creatinine were independent risk factors for mortaliy (both p < 0.05). CONCLUSION: Use of diuretics is not associated with mortality in an unselected cohort of patients presenting in an emergency room. PMID- 26832748 TI - Concomitant and multiclonal dissemination of OXA-48-producing Klebsiella pneumoniae in a Spanish hospital. PMID- 26832749 TI - Safety and effectiveness of outpatient parenteral antimicrobial therapy in older people. AB - OBJECTIVES: We analyse the safety and effectiveness of self-outpatient parenteral antimicrobial therapy (s-OPAT) in older patients. METHODS: We prospectively evaluated all adults admitted to our home hospitalization unit (HHU) for s-OPAT in the period 2008-12 in whom the bacteria responsible for the infection were identified. We divided patients into three age groups: <65, 65-79 and >=80 years. s-OPAT was administered by patients or their caregivers using elastomeric infusion devices. Effectiveness was assessed by analysing readmissions to hospital for inadequate control of underlying infection. Safety was assessed by analysing adverse events, catheter-related complications and readmission to hospital for causes unrelated to inadequate control of underlying infection. RESULTS: During the study period, 420 episodes of s-OPAT were registered in 351 patients: 139 (33.1%) in patients aged <65 years, 182 (43.3%) in those aged 65-79 years and 99 (23.6%) in those aged >=80 years. Patients aged >=80 years had a significantly lower Barthel index. The length of stay for s-OPAT and the complete HHU stay were similar in the three groups. Older people had similar changes in antibiotic treatment and hospital readmission rates due to poor control of underlying infection but higher readmission rates due to worsening of underlying diseases than younger adults. Adverse events and catheter-related complications were similar in the three age groups. CONCLUSIONS: s-OPAT administered by patients or their caregivers using elastomeric devices was safe and effective in the treatment of infections in older people. PMID- 26832750 TI - Rapid multiplexed phenotypic screening identifies drug resistance functions for three novel efflux pumps in Acinetobacter baumannii. AB - OBJECTIVES: Drug efflux pumps are one of the key machineries in bacterial drug resistance. Although quite a few of these transport systems have been functionally characterized in various organisms, due to large-scale genome sequencing efforts and improved prediction pipelines there are increasing numbers of putative drug efflux genes annotated. For phenotype identification of the proteins encoded by these genes, we developed a novel high-throughput phenotype screening strategy and demonstrated its utility in identifying phenotypes for putative efflux systems encoded by the human pathogen Acinetobacter baumannii. METHODS: Seventeen putative drug efflux systems from A. baumannii were heterologously expressed in Escherichia coli. For rapid and economical phenotype screening we employed a combination of multiplexed Biolog Phenotype Microarrays and quantitative PCR. Using this method we screened these putative drug efflux pumps against 240 antimicrobial conditions, equating to 4080 simultaneous phenotypic tests. RESULTS: Of the 17 putative drug efflux systems, phenotypes were confirmed for two pumps and novel drug resistance phenotypes were identified for three new A. baumannii drug transporters, which exemplified the power of this method as a high-throughput screening technique. One of the phenotypically characterized putative drug efflux systems was classified within the ATP-binding cassette superfamily of transport proteins and represents the first drug resistance protein characterized from this superfamily in A. baumannii. The remaining two proteins were members of the major facilitator superfamily of efflux pumps. CONCLUSIONS: This method has broad potential for high-throughput phenotype characterization of putative drug efflux systems in a range of organisms. PMID- 26832751 TI - A high-dose aminoglycoside regimen combined with renal replacement therapy for the treatment of MDR pathogens: a proof-of-concept study. AB - BACKGROUND: Infections caused by MDR Gram-negative (GN) organisms in critically ill patients are a therapeutic challenge. The administration of high-dose aminoglycoside (HDA) therapy coupled with high-flow continuous veno-venous haemodiafiltration (CVVHDF) could allow required high drug peaks to be achieved with acceptable drug elimination. METHODS: All adult patients present on the ICU between October 2009 and July 2014 who had MDR GN sepsis were considered for HDA and high-flow (>45 mL/kg/h) CVVHDF when an isolated pathogen was susceptible or had intermediate susceptibility to aminoglycosides and the patient's condition was not improving with conventional therapy. Optimal antibacterial activity was defined as a peak concentration of at least eight times the MIC. RESULTS: Fifteen patients infected with MDR GN pathogens (11 with Pseudomonas aeruginosa; 10 with abdominal infections and 5 with respiratory infections) were treated with amikacin (n = 11), gentamicin (n = 3) or tobramycin (n = 1) and high-flow CVVHDF. A favourable clinical response was observed in eight (53%) patients, including three in whom microbial eradication was obtained. Six patients were discharged alive from the ICU, and five from the hospital. No renal toxicity was observed among survivors. CONCLUSION: In this cohort of septic patients with MDR GN infections, HDA combined with high-flow CVVHDF represented a valuable therapeutic option. The effectiveness of this approach should be further evaluated in larger studies. PMID- 26832752 TI - Might isoniazid plasma exposure be a valuable predictor of drug-related hepatotoxicity risk among adult patients with TB? AB - OBJECTIVES: To investigate the relationship between isoniazid plasma exposure and the likelihood of elevation of ALT (>=51 IU/L) among adult patients with TB. METHODS: A retrospective observational study was conducted in patients who underwent periodic monitoring of hepatic function and in whom pharmacokinetic data were collected. Monte Carlo simulation was performed with the intent of identifying the probability of achieving an AUC24 greater than the identified threshold of hepatotoxicity with different dosing regimens (2.5, 5.0 and 7.5 mg/kg/day). RESULTS: Forty-one out of 185 evaluable patients (22.2%) had an ALT elevation. A mild correlation between isoniazid AUC0-24 and ALT increase was observed (Spearman's rho = 0.34, P < 0.001). Patients with ALT >=51 IU/L showed significantly higher isoniazid exposure than those with ALT <51 IU/L (mean AUC24 of 58.33 versus 31.28 mg.h/L, P < 0.001). The probabilities of ALT elevation were 0.82 and 0.12 for isoniazid AUC24 >=55.0 and <55.0 mg.h/L, respectively. Use of a logistic regression model estimated a likelihood of developing hepatotoxicity of 0.5 and 0.9 when in the presence of an isoniazid AUC24 of 53.7 and 70.0 mg.h/L, respectively. Simulation showed that the standard isoniazid 5 mg/kg daily dose gave a probability of ALT increase of 0.46 for slow acetylators and 0.03 for rapid acetylators. CONCLUSIONS: Plasma isoniazid exposure might be a valuable predictor of drug-related hepatotoxicity. Early assessment of isoniazid exposure at the beginning of treatment might allow prompt dosage reduction among those patients who are experiencing drug overexposure, thus containing the risk of hepatotoxicity occurrence. PMID- 26832754 TI - Subcutaneous ivermectin use in the treatment of severe Strongyloides stercoralis infection: two case reports and a discussion of the literature-authors' response. PMID- 26832755 TI - Susceptibility of enterohaemorrhagic Escherichia coli to azithromycin in France and analysis of resistance mechanisms. AB - OBJECTIVES: Antibiotic therapy is not recommended during enterohaemorrhagic Escherichia coli (EHEC) infection. However, the potential benefit of azithromycin has recently been described. This study was conducted to evaluate the macrolide susceptibility of EHEC isolates from France and to analyse the mechanisms of resistance to azithromycin in EHEC. METHODS: Strains from patients with EHEC infections were collected by the associated French National Reference Laboratory for E. coli from 2004 to 2014. Antimicrobial susceptibility testing was performed by disc diffusion and Etest methods. For strains presenting macrolide resistance, antibiotic resistance genes were searched for by PCR. Genetic transfer was performed by conjugation and plasmid analysis was done by Southern-blot hybridization after PFGE. RESULTS: We tested 508 isolates of EHEC. Azithromycin MICs ranged between 0.25 and 16 mg/L (median = 3 mg/L), except for two atypical strains, 34396 and 36493, for which MICs were >256 mg/L. Plasmid transferability of macrolide resistance was demonstrated. Strain 34396, of serotype O106:H18, harboured two macrolide resistance genes [mph(A) and erm(B)] and two other antimicrobial resistance genes (blaDHA-1 for beta-lactam resistance and qnrB4 for quinolone resistance). mph(A), blaDHA-1 and qnrB4 were localized on the same plasmid. Strain 36493 belonging to the highly virulent O26:H11 EHEC clonal group harboured a plasmid containing mph(A). CONCLUSIONS: For the first time we describe plasmid-borne macrolide resistance genes in EHEC strains. Dissemination of such plasmids may threaten the potential benefit of azithromycin during the management of patients infected or colonized with EHEC. Determination of azithromycin MICs should be considered prior to its therapeutic use and 16 mg/L may be used as the epidemiological cut-off value. PMID- 26832753 TI - Population pharmacokinetic drug-drug interaction pooled analysis of existing data for rifabutin and HIV PIs. AB - OBJECTIVES: Extensive but fragmented data from existing studies were used to describe the drug-drug interaction between rifabutin and HIV PIs and predict doses achieving recommended therapeutic exposure for rifabutin in patients with HIV-associated TB, with concurrently administered PIs. METHODS: Individual-level data from 13 published studies were pooled and a population analysis approach was used to develop a pharmacokinetic model for rifabutin, its main active metabolite 25-O-desacetyl rifabutin (des-rifabutin) and drug-drug interaction with PIs in healthy volunteers and patients who had HIV and TB (TB/HIV). RESULTS: Key parameters of rifabutin affected by drug-drug interaction in TB/HIV were clearance to routes other than des-rifabutin (reduced by 76%-100%), formation of the metabolite (increased by 224% in patients), volume of distribution (increased by 606%) and distribution to the peripheral compartment (reduced by 47%). For des rifabutin, clearance was reduced by 35%-76% and volume of distribution increased by 67%-240% in TB/HIV. These changes resulted in overall increased exposure to rifabutin in TB/HIV patients by 210% because of the effects of PIs and 280% with ritonavir-boosted PIs. CONCLUSIONS: Given together with non-boosted or ritonavir boosted PIs, rifabutin at 150 mg once daily results in similar or higher exposure compared with rifabutin at 300 mg once daily without concomitant PIs and may achieve peak concentrations within an acceptable therapeutic range. Although 300 mg of rifabutin every 3 days with boosted PI achieves an average equivalent exposure, intermittent doses of rifamycins are not supported by current guidelines. PMID- 26832756 TI - Treatment of Clostridium difficile infection using SQ641, a capuramycin analogue, increases post-treatment survival and improves clinical measures of disease in a murine model. AB - OBJECTIVES: Clostridium difficile infection (CDI) is a primary cause of antibiotic-associated diarrhoeal illness. Current therapies are insufficient as relapse rates following antibiotic treatment range from 25% for initial treatment to 60% for treatment of recurrence. In this study, we looked at the efficacy of SQ641 in a murine model of CDI. SQ641 is an analogue of capuramycin, a naturally occurring nucleoside-based compound produced by Streptomyces griseus. METHODS: In a series of experiments, C57BL/6 mice were treated with a cocktail of antibiotics and inoculated with C. difficile strain VPI10463. Animals were treated orally with SQ641 for 5 days at a dose range of 0.1-300 mg/kg/day, 20 mg/kg/day vancomycin or drug vehicle. Animals were monitored for disease severity, clostridial shedding and faecal toxin levels for 14 days post-infection. RESULTS: Five day treatment of CDI with SQ641 resulted in higher 14 day survival rates in mice compared with either vancomycin or vehicle alone. CDI survival rates were 100% (13 of 13) and 94% (32 of 34), respectively, in the 1 and 10 mg/kg/day SQ641 treatment groups, 37% (7 of 19) with vancomycin treatment at 20 mg/kg/day and 32% (14 of 44) in the vehicle-only control group. Secondary measures of efficacy, such as prevention of weight loss, decreased disease severity, decreased C. difficile shedding and decreased toxin in faeces, were observed with SQ641 and vancomycin treatment. CONCLUSIONS: SQ641 is effective for CDI treatment with prevention of relapse in the murine model of CDI. PMID- 26832757 TI - Pharmacokinetics and in vivo efficacy of optimized oncocin derivatives. AB - OBJECTIVES: To evaluate the efficacy of antimicrobial peptide Onc112 in a lethal Escherichia coli infection model and the pharmacokinetics of Onc72 and Onc112 administered intravenously or intraperitoneally in mice. METHODS: Onc72, Onc112 and their major metabolites in blood, kidneys, liver, brain and urine were quantified by MS using multiple reaction monitoring (MRM) and isotope-labelled peptides. RESULTS: Onc112 rescued all animals when administered intraperitoneally at a dose of 2.5 mg/kg and was thus slightly more efficient than Onc72. The MRM method provided limits of quantification in plasma, urine and kidney, liver and brain homogenates of 7-80 MUg/L, well below the MICs of 2-4 mg/L. Onc72 and Onc112 reached all organs within 10 min when administered intraperitoneally (5 mg/kg). Their initial concentrations in plasma were 11.9 and 22.6 mg/L, respectively, with elimination t1/2 values of ~14 and 21 min. The peptide concentrations in blood remained above their MICs for 20 min for Onc72 and 80 min for Onc112. The highest peptide concentrations were detected in kidney homogenates, which also contained the highest content of metabolites, indicating, together with the results from analysis of urine samples, that both peptides are cleared through the kidneys. CONCLUSIONS: Onc72 and Onc112 reach organs, including the brain, within 10 min after intravenous and intraperitoneal administration. Onc112 remained in blood at concentrations above its MIC for 80 min. The pharmacokinetic profiles explain the high in vivo efficacies in models of systemic infection and indicate the potential use of these agents for the treatment of urinary tract infections. PMID- 26832758 TI - Standard susceptibility testing overlooks potent azithromycin activity and cationic peptide synergy against MDR Stenotrophomonas maltophilia. AB - OBJECTIVES: The Gram-negative bacillus Stenotrophomonas maltophilia (SM) is an emerging MDR opportunistic pathogen. Recent studies identify a potentially relevant activity of azithromycin against Gram-negative bacteria overlooked in standard bacteriological testing. We investigated azithromycin activity against SM in testing conditions incorporating mammalian tissue culture medium and host defence factors. METHODS: MIC testing, chequerboard assays, time-kill assays and fluorescence microscopy were performed for azithromycin, the cationic peptide antibiotic colistin and the human defence peptide cathelicidin LL-37 alone or in combination in cation-adjusted Mueller-Hinton broth or mammalian tissue culture media. Azithromycin sensitization of SM to host immune clearance was tested in a human neutrophil killing assay and a murine pneumonia model. RESULTS: We observed potent bactericidal activity of azithromycin against SM in mammalian tissue culture medium absent in bacteriological medium. Colistin and LL-37 strongly potentiated azithromycin killing of SM by increasing drug entry. Additionally, azithromycin sensitized SM to neutrophil killing and increased SM clearance in the murine pneumonia model. CONCLUSIONS: Despite lack of activity in standard MIC testing, azithromycin synergizes with cationic peptide antibiotics to kill SM in medium mimicking tissue fluid conditions. Azithromycin, alone or in combination with colistin, merits further exploration in therapy of drug-resistant SM infections. PMID- 26832759 TI - Progression in children with intestinal failure at a referral hospital in Medellin, Colombia. AB - BACKGROUND: Patients with intestinal failure are unable to maintain adequate nutrition and hydration due to a reduction in the functional area of the intestine. Different strategies have the potential to benefit these patients by promoting intestinal autonomy, enhancing quality of life, and increasing survival. AIMS: To describe the clinical characteristics of children with intestinal failure and disease progression in terms of intestinal autonomy and survival. MATERIALS AND METHODS: A retrospective study was conducted, evaluating 33 pediatric patients with intestinal failure that were hospitalized within the time frame of December 2005 and December 2013 at a tertiary care referral center. Patient characteristics were described upon hospital admission, estimating the probability of achieving intestinal autonomy and calculating the survival rate. RESULTS: Patient median age upon hospital admission was 2 months (interquartile range [IQR]: 1-4 months) and 54.5% of the patients were boys. Intestinal autonomy was achieved in 69.7% of the cases with a median time of 148 days (IQR: 63 - 431 days), which decreased to 63 days in patients with a spared ileocecal valve. Survival was 91% during a median follow-up of 281 days (IQR: 161 - 772 days). CONCLUSIONS: Medical management of patients with intestinal failure is complex. Nutritional support and continuous monitoring are of the utmost importance and long-term morbidity and mortality depends on the early recognition and management of the associated complications. PMID- 26832760 TI - Effect of detrusor botulinum toxin a injection on urothelial dysfunction in patients with chronic spinal cord injury: a clinical and immunohistochemistry study before and after treatment. AB - OBJECTIVE: The objective of this study is to investigate the changes of urothelial junction proteins, apoptosis and suburothelial inflammation after detrusor injection of botulinum toxin A (BoNT-A) in patients with spinal cord injury (SCI) and neurogenic detrusor overactivity (NDO). METHODS: A total of 26 patients with chronic suprasacral SCI and NDO were enroled. The urothelium was assessed by cystoscopic biopsy at baseline, 3 and 6 months after a single treatment of 300 U BoNT-A into the detrusor. Immunofluorescence staining of E cadherin, zonula occludens-1 (ZO-1) and tryptase for mast cell activity were performed. Urothelial apoptosis was also evaluated. The differences in urothelial dysfunction were compared between baseline and 3 and 6 months after treatment. Bladder biopsies from patients undergoing anti-incontinence surgery served as controls. RESULTS: A single 300-U BoNT-A injection into the detrusor significantly decreased detrusor pressure and increased bladder compliance at 3 and 6 months after treatment. Significantly lower E-cadherin and ZO-1 expressions and increased mast cell and apoptotic cell counts were noted in SCI bladders compared with controls (all P<0.001). Significantly greater distributions of E cadherin (P<0.001) and ZO-1 (P=0.05) expressions were noted 3 months after BoNT-A injection. However, these changes had declined by 6 months after treatment. Activated mast cells and urothelial apoptosis showed no significant differences between baseline and 3 or 6 months. CONCLUSION: Urothelial dysfunction and adhesive and junction protein concentrations in SCI patients' bladders recovered after BoNT-A treatment. However, this effect decreased with time. Thus, neurogenic inflammation after SCI was not adequately improved after a single BoNT A injection. PMID- 26832761 TI - Prenatal polybrominated diphenyl ether and perfluoroalkyl substance exposures and executive function in school-age children. AB - Executive function is a critical behavioral trait rarely studied in relation to potential neurotoxicants. Prenatal exposure to polybrominated diphenyl ethers (PBDEs) and perfluoroalkyl substances (PFASs) has been associated with adverse neurodevelopment, but there is limited research on executive function. Data from 256 mother-child pairs in the Health Outcomes and Measures of the Environment Study, a prospective birth cohort (2003-2006, Cincinnati, OH), was used to examine maternal serum PBDEs and PFASs and executive function in children ages 5 and 8 years. Maternal serum PBDEs and PFASs were measured at 16+/-3 weeks gestation. Executive function was assessed with the parent-rated Behavior Rating Inventory of Executive Function (BRIEF), which yields composite measures: behavioral regulation index, metacognition index, and global executive composite. Higher BRIEF scores indicate executive function impairments. Linear mixed models and generalized estimating equations were used to estimate covariate-adjusted associations between PBDEs and PFASs and executive function. A 10-fold increase in BDE-153 was associated with poorer behavior regulation (beta=3.23, 95% CI 0.60, 5.86). Higher odds of having a score >=60 in behavior regulation (OR=3.92, 95% CI 1.76, 8.73) or global executive functioning (OR=2.34, 95% CI 1.05, 5.23) was observed with increased BDE-153. Each ln-unit increase in perfluorooctane sulfonate (PFOS) was associated with poorer behavior regulation (beta=3.14, 95% CI 0.68, 5.61), metacognition (beta=3.10, 95% CI 0.62, 5.58), and global executive functioning (beta=3.38, 95% CI 0.86, 5.90). However, no association was observed between perfluorooctanoate (PFOA) and executive function. Prenatal exposures to BDE-153 and PFOS may be associated with executive function deficits in school-age children. PMID- 26832770 TI - Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas. AB - Synchronous early-stage endometrioid endometrial carcinomas (EECs) and endometrioid ovarian carcinomas (EOCs) are associated with a favorable prognosis and have been suggested to represent independent primary tumors rather than metastatic disease. We subjected sporadic synchronous EECs/EOCs from five patients to whole-exome massively parallel sequencing, which revealed that the EEC and EOC of each case displayed strikingly similar repertoires of somatic mutations and gene copy number alterations. Despite the presence of mutations restricted to the EEC or EOC in each case, we observed that the mutational processes that shaped their respective genomes were consistent. High-depth targeted massively parallel sequencing of sporadic synchronous EECs/EOCs from 17 additional patients confirmed that these lesions are clonally related. In an additional Lynch Syndrome case, however, the EEC and EOC were found to constitute independent cancers lacking somatic mutations in common. Taken together, sporadic synchronous EECs/EOCs are clonally related and likely constitute dissemination from one site to the other. PMID- 26832771 TI - Synchronous Endometrial and Ovarian Carcinomas: Evidence of Clonality. AB - Many women with ovarian endometrioid carcinoma present with concurrent endometrial carcinoma. Organ-confined and low-grade synchronous endometrial and ovarian tumors (SEOs) clinically behave as independent primary tumors rather than a single advanced-stage carcinoma. We used 18 SEOs to investigate the ancestral relationship between the endometrial and ovarian components. Based on both targeted and exome sequencing, 17 of 18 patient cases of simultaneous cancer of the endometrium and ovary from our series showed evidence of a clonal relationship, ie, primary tumor and metastasis. Eleven patient cases fulfilled clinicopathological criteria that would lead to classification as independent endometrial and ovarian primary carcinomas, including being of FIGO stage T1a/1A, with organ-restricted growth and without surface involvement; 10 of 11 of these cases showed evidence of clonality. Our observations suggest that the disseminating cells amongst SEOs are restricted to physically accessible and microenvironment-compatible sites yet remain indolent, without the capacity for further dissemination. PMID- 26832772 TI - Making a Difference: Distinguishing Two Primaries From Metastasis in Synchronous Tumors of the Ovary and Uterus. AB - For women with early-stage ovarian or endometrial cancers, prognosis is very good, with overall survival for both sites between 80% and 90%. This stands in stark contrast to metastatic disease (advanced stage), where the overall survival is less than 15%. We have long recognized that subtypes of disease also inform these statistics, with high-grade serous carcinomas conferring a far worse prognosis compared with others, including low-grade serous or endometrioid tumors. Yet even with our present understanding, a not uncommon finding is the diagnosis of women with carcinoma at both the ovary and the uterus (a situation that occurs in up to 10% of patients), raising the question of synchronous primaries or of metastatic disease. The implications of these clinical scenarios are very relevant: If a conclusion of synchronous primaries is made, then prognosis should be excellent and hence no further treatment beyond surgery is required for cure. However, the finding of metastatic disease (from the ovary to the uterus or vice versa) will substantially change the prognostic implications, with these patients having a higher risk of recurrence and death from metastatic disease. In addition, this differential diagnosis can change therapeutic recommendations, with metastatic disease requiring more aggressive adjuvant therapy. Thus, the issue is both a biologic and clinical one. PMID- 26832773 TI - HABP2 G534E Mutation in Familial Nonmedullary Thyroid Cancer. AB - Papillary thyroid cancer (PTC) is a common endocrine malignancy, accounting for nearly 90% of all thyroid cancers. About 5% of PTC is hereditary familial nonmedullary thyroid cancer (FNMTC). No general susceptibility gene is known for FNMTC. An oncogenic HABP2 G534E mutation has been recently reported in one FNMTC kindred, suggesting that HABP2 is a susceptibility gene for FNMTC. Because of the limited kindred studied, how commonly this gene is responsible-and hence how important clinically it is-for FNMTC remains to be answered. By investigating a large number of FNMTC kindreds in the present study, we identified HABP2 G534E in several independent kindreds of FNMTC. The overall prevalence of HABP2 G534E was six per 43 (14.0%) PTC patients from the 29 kindreds and four per 29 (13.8%) kindreds. None of the subjects with benign thyroid neoplasm or the normal subjects from these kindreds had this mutation. These results are consistent with HABP2 G534E being a susceptibility gene in a subgroup of FNMTC, providing important diagnostic implications for this hereditary thyroid cancer. PMID- 26832774 TI - HABP2 in Familial Non-medullary Thyroid Cancer: Will the Real Mutation Please Stand Up? PMID- 26832775 TI - Phenotypic Heterogeneity in a DFNA20/26 family segregating a novel ACTG1 mutation. AB - BACKGROUND: Genetic factors play an important role in hearing loss, contributing to approximately 60% of cases of congenital hearing loss. Autosomal dominant deafness accounts for approximately 20% of cases of hereditary hearing loss. Diseases with autosomal dominant inheritance often show pleiotropy, different degrees of penetrance, and variable expressivity. METHODS: A three-generation Chinese family with autosomal dominant nonsyndromic hearing impairment (ADNSHI) was enrolled in this study. Audiometric data and blood samples were collected from the family. In total, 129 known human deafness genes were sequenced using next-generation sequencing (NGS) to identify the responsible gene mutation in the family. Whole Exome Sequencing (WES) was performed to exclude any other variant that cosegregated with the phenotype. RESULTS: The age of onset of the affected family members was the second decade of life. The condition began with high frequency hearing impairment in all family members excluding III:2. The novel ACTG1 c.638A > G (p.K213R) mutation was found in all affected family members and was not found in the unaffected family members. A heterozygous c.638A > G mutation in ACTG1 and homozygous c.109G > A (p.V37I) mutation in GJB2 were found in III:2, who was born with hearing loss. The WES result concurred with that of targeted sequencing of known deafness genes. CONCLUSIONS: The novel mutation p.K213R in ACTG1 was found to be co-segregated with hearing loss and the genetic cause of ADNSHI in this family. A homozygous mutation associated with recessive inheritance only rarely co-acts with a dominant mutation to result in hearing loss in a dominant family. In such cases, the mutations in the two genes, as in ACTG1 and GJB2 in the present study, may result in a more severe phenotype. Targeted sequencing of known deafness genes is one of the best choices to identify the genetic cause in hereditary hearing loss families. PMID- 26832776 TI - Who reads Clinics and Research in Hepatology and Gastroenterology? PMID- 26832777 TI - Genetic Differential Susceptibility to Socioeconomic Status and Childhood Obesogenic Behavior: Why Targeted Prevention May Be the Best Societal Investment. AB - IMPORTANCE: Genes may work by modulating the way individuals respond to environmental variation, and these discrete and differential genes vs environmental interactions may not be readily captured in simple association studies. OBJECTIVE: To determine whether children carrying the 7-repeat allele of the DRD4 gene living under adverse economic conditions have worse-than-average fat intake compared with those living in a healthy environment. DESIGN, SETTING, AND PARTICIPANTS: Data from an established prospective birth cohort (Maternal Adversity, Vulnerability, and Neurodevelopment) were used to study 4-year-old children from Montreal, Quebec, Canada and Hamilton, Ontario, Canada. A total of 190 children (94 girls and 96 boys) had height and weight measured and complete food diaries and were therefore eligible for the study. The study is derived from a birth cohort started in June 2003 and still ongoing. The last age of follow-up was at 6 years. EXPOSURES: Social environment was characterized based on the gross family income, and DNA was genotyped for the 7-repeat allele of the DRD4 gene. MAIN OUTCOMES AND MEASURES: Fat intake. RESULTS: The 5 steps to distinguish the differential susceptibility from other types of interaction were followed, and the study confirms that differential susceptibility is a relevant model to address the association between the 7-repeat allele of DRD4 and food choices in girls. Of the 190 children, 112 did not have the DRD4 7-repeat allele and 78 did. Baseline characteristics did not differ in these 2 groups. Although not different in several confounders, such as maternal educational level, maternal smoking during gestation, birth weight, and breastfeeding duration, girls carrying the 7 repeat allele of the DRD4 gene and living in adverse socioeconomic conditions have increased fat intake compared with girls who are noncarriers (DRD4 7+ mean, 33.95% of calories derived from fat; 95% CI, 28.76%-39.13%; DRD4 7- mean, 28.76%; 95% CI, 26.77%-30.83%). However, girls carrying the 7-repeat allele of the same gene and living in better socioeconomic conditions have decreased fat intake compared with noncarriers (DRD4 7+ mean, 29.03% of calories derived from fat; 95% CI, 26.69%-31.51%; DRD4 7- mean, 31.88%; 95% CI, 30.28%-33.58%). CONCLUSIONS AND RELEVANCE: Alleles previously considered to be obesity risk alleles might in fact function as plasticity alleles, determining openness to environmental modification and/or intervention, as seen in the girls in this study. This finding has important implications for obesity prevention and social pediatrics. PMID- 26832779 TI - Electronic central bearing point as registration method in individuals with and without temporomandibular disorders. AB - OBJECTIVES: The aim of this study was to examine different central bearing point methods in patients with and without temporomandibular disorders (TMD) by an experienced and unexperienced examiner. MATERIAL AND METHODS: The 20 fully dentulous subjects were screened for TMD based on the Research Diagnostic Criteria for TMD and distinguished into functional impaired and functional healthy groups. The mandibular relationship was recorded by an electronic central bearing tracing device (IPR-System, IPR GmbH, Oldenburg, Germany) with an integrated pressure sensor. Three bite registration methods were performed using this device: initial neuromuscular position, final neuromuscular position after dynamic sequences with the intraoral pin (=neuromuscular deprogramming), and centric relation guided manually by an experienced and an unexperienced examiner. RESULTS: The neuromuscular positions before and after neuromuscular deprogramming were not significantly different (paired t test as a group comparison test: transverse: p = 0.369; sagittal: p = 0.486). Both positions were significantly anterior in comparison to the manually guided centric relation (paired t test as a group comparison test: p < 0.0001). The neuromuscular positions before and after deprogramming tend to have high scattering values. CONCLUSION: By means of the central bearing point method, the manually guided centric relation is the one which is sufficiently reproducible. It seems doubtful to take the significant anterior neuromuscular position for a definite reconstruction. CLINICAL RELEVANCE: Using the central bearing point method, the manually guided centric relation should be preferred, whereas the neuromuscular position should not be used for definite reconstructions. PMID- 26832778 TI - A paneukaryotic genomic analysis of the small GTPase RABL2 underscores the significance of recurrent gene loss in eukaryote evolution. AB - BACKGROUND: The cilium (flagellum) is a complex cellular structure inherited from the last eukaryotic common ancestor (LECA). A large number of ciliary proteins have been characterized in a few model organisms, but their evolutionary history often remains unexplored. One such protein is the small GTPase RABL2, recently implicated in the assembly of the sperm tail in mammals. RESULTS: Using the wealth of currently available genome and transcriptome sequences, including data from our on-going sequencing projects, we systematically analyzed the phylogenetic distribution and evolutionary history of RABL2 orthologs. Our dense taxonomic sampling revealed the presence of RABL2 genes in nearly all major eukaryotic lineages, including small "obscure" taxa such as breviates, ancyromonads, malawimonads, jakobids, picozoans, or palpitomonads. The phyletic pattern of RABL2 genes indicates that it was present already in the LECA. However, some organisms lack RABL2 as a result of secondary loss and our present sampling predicts well over 30 such independent events during the eukaryote evolution. The distribution of RABL2 genes correlates with the presence/absence of cilia: not a single well-established cilium-lacking species has retained a RABL2 ortholog. However, several ciliated taxa, most notably nematodes, some arthropods and platyhelminths, diplomonads, and ciliated subgroups of apicomplexans and embryophytes, lack RABL2 as well, suggesting some simplification in their cilium-associated functions. On the other hand, several algae currently unknown to form cilia, e.g., the "prasinophytes" of the genus Prasinoderma or the ochrophytes Pelagococcus subviridis and Pinguiococcus pyrenoidosus, turned out to encode not only RABL2, but also homologs of some hallmark ciliary proteins, suggesting the existence of a cryptic flagellated stage in their life cycles. We additionally obtained insights into the evolution of the RABL2 gene architecture, which seems to have ancestrally consisted of eight exons subsequently modified not only by lineage-specific intron loss and gain, but also by recurrent loss of the terminal exon encoding a poorly conserved C-terminal extension. CONCLUSIONS: Our comparative analysis supports the notion that RABL2 is an ancestral component of the eukaryotic cilium and underscores the still underappreciated magnitude of recurrent gene loss, or reductive evolution in general, in the history of eukaryotic genomes and cells. PMID- 26832780 TI - Efficacy of fluoride varnish for preventing white spot lesions and gingivitis during orthodontic treatment with fixed appliances-a prospective randomized controlled trial. AB - OBJECTIVES: The development of white spot lesions around orthodontic brackets and gingivitis is a common problem during orthodontic treatment with fixed appliances. This prospective randomized double-blind controlled clinical trial investigated the preventive efficacy of a one-time application of two commonly used fluoride varnishes in patients with low to moderate caries risk. MATERIALS AND METHODS: Ninety adolescent orthodontic patients with a low to moderate caries risk were prospectively randomized to three groups of 30 patients each: (1) standardized dental hygiene with fluoride toothpaste and one-time application of placebo varnish (control) or (2) of elmex(r) fluid or (3) of Fluor Protector S on all dental surfaces at the start of fixed therapy. The extent of enamel demineralization and gingivitis was determined with the ICDAS and the gingivitis index (GI) at baseline and after 4, 12, and 20 weeks. RESULTS: Each treatment group showed a significant increase of the ICDAS index, but not of the GI over the course of time with no significant intergroup differences detectable. CONCLUSIONS: A one-time application of fluoride varnish at the start of orthodontic treatment did not provide any additional preventive advantage over sufficient dental hygiene with fluoride toothpaste with regard to formation of white spots and gingivitis in patients with a low to moderate caries risk. CLINICAL RELEVANCE: In dental practice, patients often receive an application of fluoride varnish at the start of orthodontic treatment with fixed appliances. However, the efficacy of this procedure is still unclear. PMID- 26832781 TI - Zinc-modified nanopolymers improve the quality of resin-dentin bonded interfaces. AB - INTRODUCTION: Demineralized collagen fibers at the hybrid layer are susceptible to degradation. Remineralization may aid to improve bond longevity. OBJECTIVES: The aim of the present study was to infiltrate zinc and calcium-loaded polymeric nanoparticles into demineralized dentin to facilitate hybrid layer remineralization. MATERIALS AND METHODS: Zinc or calcium-loaded polymeric nanoparticles were infiltrated into etched dentin, and Single Bond Adhesive was applied. Bond strength was tested after 24 h and 6 months storage. Nanomechanical properties, dye-assisted confocal laser microscopy, and Masson's trichrome staining evaluation were performed to assess for the hybrid layer morphology, permeability, and remineralization ability after 24 h and 3 months. Data were analyzed by ANOVA and Student-Newman-Keuls multiple comparisons tests (p < 0.05). RESULTS: Immediate bond strength was not affected by nanoparticles infiltration (25 to 30 MPa), while after 6 months, bond strengths were maintained (22 to 24 MPa). After 3 months, permeability occurred only in specimens in which nanoparticles were not infiltrated. Dentin remineralization, at the bottom of the hybrid layer, was observed in all groups. After microscopy analysis, zinc-loaded nanoparticles were shown to facilitate calcium deposition throughout the entire hybrid layer. Young's modulus at the hybrid layer increased from 2.09 to 3.25 GPa after 3 months, in specimens with zinc nanoparticles; meanwhile, these values were reduced from 1.66 to 0.49 GPa, in the control group. CONCLUSION: Infiltration of polymeric nanoparticles into demineralized dentin increased long term bond strengths. Zinc-loaded nanoparticles facilitate dentin remineralization within the complete resin-dentin interface. CLINICAL RELEVANCE: Resin-dentin bond longevity and dentin remineralization at the hybrid layer were facilitated by zinc-loaded nanoparticles. PMID- 26832782 TI - Pro-inflammatory cytokines at zirconia implants and teeth. A cross-sectional assessment. AB - OBJECTIVES: The aim of this study was to compare the expression of host-derived markers in peri-implant/gingival crevicular fluid (PCF/GCF) and clinical conditions at ceramic implants and contralateral natural teeth. As a secondary objective, we compared zirconia implants with titanium implants. METHODS: One zirconia implant (ZERAMEX(r) Implant System) and one contralateral natural tooth were examined in 36 systemically healthy subjects (21 males, 15 females, mean age 58). The levels of Il-1beta, Il-1RA, Il-6, Il-8, Il-17, b-FGF, G-CSF, GM-CSF, IFNgamma, MIP-1beta, TNF-alpha, and VEGF were assessed in PCF/GCF using the Bio Plex 200 Suspension Array System. The plaque index (PI), gingival index (GI), probing depth (PD), and bleeding on probing (BOP) were assessed at six sites around each implant or tooth. Titanium implants were also assessed when present (n = 9). RESULTS: The zirconia implants were examined after a loading period of at least 1.2 years (average 2.2 years). The mean PI was significantly lower at zirconia implants compared to teeth (p = 0.003), while the mean GI, PD, and BOP were significantly higher (p < 0.001). A correlation was found in the expression of Il-1RA, Il-8, G-CSF, MIP-1beta, and TNF-alpha at zirconia implants and teeth. The levels of IL-1beta and TNF-alpha were significantly higher at zirconia implants than at teeth. No significant differences were found between zirconia and titanium implants. A correlation was found between the levels of IL-1RA, IL 8, GM-CSF, and MIP-1beta at zirconia and titanium implants. CONCLUSIONS: The correlation in the expression of five biomarkers at zirconia implants and teeth, and of four biomarkers at zirconia and titanium implants, is compatible with the existence of a patient-specific inflammatory response pattern. Higher mean GI, PD, and BOP around implants suggests that the peri-implant mucosa may be mechanically more fragile than the gingiva. CLINICAL RELEVANCE: Similar expression of selected biomarkers at zirconia implants and teeth and at zirconia and titanium implants reflects existence of patient-specific inflammatory response patterns. PMID- 26832783 TI - Mechanical properties of bone tissues surrounding dental implant systems with different treatments and healing periods. AB - OBJECTIVES: The objective of the current study was to examine whether the nanoindentation parameters can assess the alteration of bone quality resulting from different degrees of bone remodeling between bone tissue ages around the dental implant interface with different treatments and healing periods. MATERIALS AND METHODS: Dental implants were placed in mandibles of six male dogs. Treatment groups included: resorbable blast media-treated titanium (Ti) implants, alumina blasted zirconia implants (ATZ), alumina-blasted zirconia implants applied with demineralized bone matrix (ATZ-D), and alumina-blasted zirconia implants applied with rhBMP-2 (ATZ-B). Nanoindentation modulus (E), hardness (H), viscosity (eta), and viscoelastic creep (Creep/P max) were measured for new and old bone tissues adjacent to the implants at 3 and 6 weeks of post-implantation. A total of 945 indentations were conducted for 32 implant systems. RESULTS: Significantly lower E, H, and eta but higher Creep/P max were measured for new bone tissues than old bone tissues, independent of treatments at both healing periods (p < 0.001). All nanoindentation parameters were not significantly different between healing periods (p > 0.568). ATZ-D and ATZ-B implants had the stiffer slope of correlation between E and Creep/P max of the new bone tissue than Ti implant (p < 0.039). CONCLUSIONS: Current results indicated that, in addition to elastic modulus and plastic hardness, measurement of viscoelastic properties of bone tissue surrounding the implant can provide more detailed information to understand mechanical behavior of an implant system. CLINICAL RELEVANCE: Ability of energy absorption in the interfacial bone tissue can play a significant role in the long-term success of a dental implant system. PMID- 26832785 TI - Carbohydrate-based inducers of cellular stress for targeting cancer cells. AB - Small molecules that block the altered metabolism in cancer or increase the production of reactive oxygen species (ROS) are emerging as potential anti-cancer agents. Considering that various carbohydrates can be used for cellular energetics or protein N-glycosylation of which interruption can lead to cellular stress, we have synthesized and evaluated a library of N-aryl glycosides for induction of ROS and cytotoxicity in H1299 cancer cell line. Two N-aryl glycosides (K8 and H8) were identified that induce about 2-fold induction of ROS and cytotoxicity in H1299 cells. We further showed that the acetylated form of K8 (K8A) activates AMPK, and stabilizes p53 in HEK293 cells, and induce a higher cytotoxicity than 2-deoxy-d-glucose in H1299 cell line. PMID- 26832784 TI - Design and synthesis of novel hybrid sydnonimine and prodrug useful for glaucomatous optic neuropathy. AB - Synthesis and bioactivity of novel dual acting nitric oxide releasing and reactive oxygen scavenging hybrid compound SA-2 is described. The hybrid molecule SA-2 significantly increased the superoxide dismutase enzyme level and protected the photoreceptor cells from H2O2 induced oxidative stress. Synthesis of ocular esterase sensitive aceloxy alkyl carbamate prodrug SA-4 with improved aqueous half-life is achieved to aid topical ocular formulation. This class of hybrid molecule and prodrug may have dual potential of improved IOP lowering and neuroprotection in glaucomatous optic neuropathy. PMID- 26832786 TI - Synthesis and SAR of 4-methyl-5-pentylbenzene-1,3-diol (MPBD), produced by Dictyostelium discoideum. AB - 4-Methyl-5-pentylbenzene-1,3-diol (MPBD) is a secondary metabolite of SteelyA polyketide synthase, which controls cell aggregation and spore maturation of Dictyostelium discoideum. In this study, chemical synthesis of MPBD and its derivatives was achieved. Structure-activity relationship (SAR) studies for antimicrobial activities against Escherichia coli and Bacillus subtilis were also conducted. PMID- 26832788 TI - Measuring ultrasound images of abdominal and lumbar multifidus muscles in older adults: A reliability study. AB - Measurement reliability of the L4/5 lumbar multifidus (MF) muscles is high in older adults, but few studies have investigated measurement reliability of the abdominal and upper lumbar MF muscles in this age group. OBJECTIVES: To determine measurement reliability of abdominal and lumbar MF muscles from a single ultrasound (US) image in older adults. METHODS: Resting thickness of rectus abdominis and obliquus externus, resting and contracted thickness of obliquus internus, transversus abdominis and lumbar MF, and resting cross-sectional area (CSA) of MF levels (L2-5) were obtained from US images of 92 community-dwelling older adults (aged 65-89 years). Measurements of images were undertaken by an experienced rater and repeated 7-10 days later for intra-rater, and by a second expert rater for inter-rater calculations. Intra-rater reliability was estimated for all muscles. Inter-rater reliability was estimated for all abdominal muscles and for L5 multifidus. Reliability was estimated by intraclass correlation coefficients (ICC). RESULTS: Intra-rater ICC(3,1) and inter-rater ICC(2,1) of resting thickness measures of all muscles and CSA of MF were >=0.86. The ICCs for percentage thickness change were >=0.76 for the abdominal muscles, and >=0.42 for MF. CONCLUSIONS: Measurement reliability of US imaging for abdominal and MF muscle thickness and MF CSA was high, and consistent with previous findings for younger adults. Reliability of percentage thickness change was lower suggesting caution is needed when using this as an outcome measure or study factor among older adults. PMID- 26832789 TI - On Being a 21st Century Patient. PMID- 26832787 TI - Evaluation of synthetic coumarins for antiausterity cytotoxicity against pancreatic cancers. AB - A series of functionalized coumarins were synthesized and evaluated for their capacity to inhibit the resistance to starvation of pancreatic cancer cells. This form of cytotoxicity, termed 'antiausterity' activity, was evaluated using a preferential cytotoxicity assay that compared cell survival in nutrient poor and nutrient rich conditions. Six of the seventeen compounds showed weak antiausterity activity against PANC-1. Compound 34 was active against PANC-1, MIA PaCa-2, and Capan-1 cancer cell lines. All of the compounds tested were simplified structural analogs of previously reported natural product leads. Six of the compounds, including 34, contain functionalized triazoles as novel potential bioisosteres of the side chain of the natural product angelmarin. Overall, the analogs were found to have low antiausterity activity relative to the corresponding natural products. PMID- 26832790 TI - Targeting the Nuclear Import Receptor Kpnbeta1 as an Anticancer Therapeutic. AB - Karyopherin beta 1 (Kpnbeta1) is a nuclear transport receptor that imports cargoes into the nucleus. Recently, elevated Kpnbeta1 expression was found in certain cancers and Kpnbeta1 silencing with siRNA was shown to induce cancer cell death. This study aimed to identify novel small molecule inhibitors of Kpnbeta1, and determine their anticancer activity. An in silico screen identified molecules that potentially bind Kpnbeta1 and Inhibitor of Nuclear Import-43, INI-43 (3-(1H benzimidazol-2-yl)-1-(3-dimethylaminopropyl)pyrrolo[5,4-b]quinoxalin-2-amine) was investigated further as it interfered with the nuclear localization of Kpnbeta1 and known Kpnbeta1 cargoes NFAT, NFkappaB, AP-1, and NFY and inhibited the proliferation of cancer cells of different tissue origins. Minimum effect on the proliferation of noncancer cells was observed at the concentration of INI-43 that showed a significant cytotoxic effect on various cervical and esophageal cancer cell lines. A rescue experiment confirmed that INI-43 exerted its cell killing effects, in part, by targeting Kpnbeta1. INI-43 treatment elicited a G2-M cell cycle arrest in cancer cells and induced the intrinsic apoptotic pathway. Intraperitoneal administration of INI-43 significantly inhibited the growth of subcutaneously xenografted esophageal and cervical tumor cells. We propose that Kpnbeta1 inhibitors could have therapeutic potential for the treatment of cancer. Mol Cancer Ther; 15(4); 560-73. (c)2016 AACR. PMID- 26832791 TI - Novel Mps1 Kinase Inhibitors with Potent Antitumor Activity. AB - Monopolar spindle 1 (Mps1) has been shown to function as the key kinase that activates the spindle assembly checkpoint (SAC) to secure proper distribution of chromosomes to daughter cells. Here, we report the structure and functional characterization of two novel selective Mps1 inhibitors, BAY 1161909 and BAY 1217389, derived from structurally distinct chemical classes. BAY 1161909 and BAY 1217389 inhibited Mps1 kinase activity with IC50 values below 10 nmol/L while showing an excellent selectivity profile. In cellular mechanistic assays, both Mps1 inhibitors abrogated nocodazole-induced SAC activity and induced premature exit from mitosis ("mitotic breakthrough"), resulting in multinuclearity and tumor cell death. Both compounds efficiently inhibited tumor cell proliferation in vitro (IC50 nmol/L range). In vivo, BAY 1161909 and BAY 1217389 achieved moderate efficacy in monotherapy in tumor xenograft studies. However, in line with its unique mode of action, when combined with paclitaxel, low doses of Mps1 inhibitor reduced paclitaxel-induced mitotic arrest by the weakening of SAC activity. As a result, combination therapy strongly improved efficacy over paclitaxel or Mps1 inhibitor monotreatment at the respective MTDs in a broad range of xenograft models, including those showing acquired or intrinsic paclitaxel resistance. Both Mps1 inhibitors showed good tolerability without adding toxicity to paclitaxel monotherapy. These preclinical findings validate the innovative concept of SAC abrogation for cancer therapy and justify clinical proof-of-concept studies evaluating the Mps1 inhibitors BAY 1161909 and BAY 1217389 in combination with antimitotic cancer drugs to enhance their efficacy and potentially overcome resistance. Mol Cancer Ther; 15(4); 583-92. (c)2016 AACR. PMID- 26832792 TI - Inhibition of HSP90 by AUY922 Preferentially Kills Mutant KRAS Colon Cancer Cells by Activating Bim through ER Stress. AB - Oncogenic mutations of KRAS pose a great challenge in the treatment of colorectal cancer. Here we report that mutant KRAS colon cancer cells are nevertheless more susceptible to apoptosis induced by the HSP90 inhibitor AUY922 than those carrying wild-type KRAS. Although AUY922 inhibited HSP90 activity with comparable potency in colon cancer cells irrespective of their KRAS mutational statuses, those with mutant KRAS were markedly more sensitive to AUY922-induced apoptosis. This was associated with upregulation of the BH3-only proteins Bim, Bik, and PUMA. However, only Bim appeared essential, in that knockdown of Bim abolished, whereas knockdown of Bik or PUMA only moderately attenuated apoptosis induced by AUY922. Mechanistic investigations revealed that endoplasmic reticulum (ER) stress was responsible for AUY922-induced upregulation of Bim, which was inhibited by a chemical chaperone or overexpression of GRP78. Conversely, siRNA knockdown of GRP78 or XBP-1 enhanced AUY922-induced apoptosis. Remarkably, AUY922 inhibited the growth of mutant KRAS colon cancer xenografts through activation of Bim that was similarly associated with ER stress. Taken together, these results suggest that AUY922 is a promising drug in the treatment of mutant KRAS colon cancers, and the agents that enhance the apoptosis-inducing potential of Bim may be useful to improve the therapeutic efficacy. PMID- 26832793 TI - SPARC-Independent Delivery of Nab-Paclitaxel without Depleting Tumor Stroma in Patient-Derived Pancreatic Cancer Xenografts. AB - The study goal was to examine the relationship between nab-paclitaxel delivery and SPARC (secreted protein acidic and rich in cysteine) expression in pancreatic tumor xenografts and to determine the antistromal effect of nab-paclitaxel, which may affect tumor vascular perfusion. SPARC-positive and -negative mice bearing Panc02 tumor xenografts (n = 5-6/group) were injected with IRDye 800CW (IR800) labeled nab-paclitaxel. After 24 hours, tumors were collected and stained with DL650-labeled anti-SPARC antibody, and the correlation between nab-paclitaxel and SPARC distributions was examined. Eight groups of mice bearing either Panc039 or Panc198 patient-derived xenografts (PDX; 4 groups/model, 5 animals/group) were untreated (served as control) or treated with gemcitabine (100 mg/kg body weight, i.p., twice per week), nab-paclitaxel (30 mg/kg body weight, i.v., for 5 consecutive days), and these agents in combination, respectively, for 3 weeks, and tumor volume and perfusion changes were assessed using T2-weighted MRI and dynamic contrast-enhanced (DCE) MRI, respectively. All tumors were collected and stained with Masson's Trichrome Stain, followed by a blinded comparative analysis of tumor stroma density. IR800-nab-paclitaxel was mainly distributed in tumor stromal tissue, but nab-paclitaxel and SPARC distributions were minimally correlated in either SPARC-positive or -negative animals. Nab-paclitaxel treatment neither decreased tumor stroma nor increased tumor vascular perfusion in either PDX model when compared with control groups. These data suggest that the specific tumor delivery of nab-paclitaxel is not directly related to SPARC expression, and nab-paclitaxel does not deplete tumor stroma in general. Mol Cancer Ther; 15(4); 680-8. (c)2016 AACR. PMID- 26832794 TI - EGFR Is Regulated by TFAP2C in Luminal Breast Cancer and Is a Target for Vandetanib. AB - Expression of TFAP2C in luminal breast cancer is associated with reduced survival and hormone resistance, partially explained through regulation of RET. TFAP2C also regulates EGFR in HER2 breast cancer. We sought to elucidate the regulation and functional role of EGFR in luminal breast cancer. We used gene knockdown (KD) and treatment with a tyrosine kinase inhibitor (TKI) in cell lines and primary cancer isolates to determine the role of RET and EGFR in regulation of p-ERK and tumorigenesis. KD of TFAP2C decreased expression of EGFR in a panel of luminal breast cancers, and chromatin immunoprecipitation sequencing (ChIP-seq) confirmed that TFAP2C targets the EGFR gene. Stable KD of TFAP2C significantly decreased cell proliferation and tumor growth, mediated in part through EGFR. While KD of RET or EGFR reduced proliferation (31% and 34%, P < 0.01), combined KD reduced proliferation greater than either alone (52% reduction, P < 0.01). The effect of the TKI vandetanib on proliferation and tumor growth response of MCF-7 cells was dependent upon expression of TFAP2C, and dual KD of RET and EGFR eliminated the effects of vandetanib. The response of primary luminal breast cancers to TKIs assessed by ERK activation established a correlation with expression of RET and EGFR. We conclude that TFAP2C regulates EGFR in luminal breast cancer. Response to vandetanib was mediated through the TFAP2C target genes EGFR and RET. Vandetanib may provide a therapeutic effect in luminal breast cancer, and RET and EGFR can serve as molecular markers for response. PMID- 26832796 TI - Chemical Inhibition of Wild-Type p53-Induced Phosphatase 1 (WIP1/PPM1D) by GSK2830371 Potentiates the Sensitivity to MDM2 Inhibitors in a p53-Dependent Manner. AB - Sensitivity to MDM2 inhibitors is widely different among responsive TP53 wild type cell lines and tumors. Understanding the determinants of MDM2 inhibitor sensitivity is pertinent for their optimal clinical application. Wild-type p53 inducible phosphatase-1 (WIP1) encoded by PPM1D, is activated, gained/amplified in a range of TP53 wild-type malignancies, and is involved in p53 stress response homeostasis. We investigated cellular growth/proliferation of TP53 wild-type and matched mutant/null cell line pairs, differing in PPM1D genetic status, in response to Nutlin-3/RG7388 +/- a highly selective WIP1 inhibitor, GSK2830371. We also assessed the effects of GSK2830371 on MDM2 inhibitor-induced p53(Ser15) phosphorylation, p53-mediated global transcriptional activity, and apoptosis. The investigated cell line pairs were relatively insensitive to single-agent GSK2830371. However, a non-growth-inhibitory dose of GSK2830371 markedly potentiated the response to MDM2 inhibitors in TP53 wild-type cell lines, most notably in those harboring PPM1D-activating mutations or copy number gain (up to 5.8-fold decrease in GI50). Potentiation also correlated with significant increase in MDM2 inhibitor-induced cell death endpoints that were preceded by a marked increase in a WIP1 negatively regulated substrate, phosphorylated p53(Ser15), known to increase p53 transcriptional activity. Microarray-based gene expression analysis showed that the combination treatment increases the subset of early RG7388-induced p53 transcriptional target genes. These findings demonstrate that potent and selective WIP1 inhibition potentiates the response to MDM2 inhibitors in TP53 wild-type cells, particularly those with PPM1D activation or gain, while highlighting the mechanistic importance of p53(Ser15) and its potential use as a biomarker for response to this combination regimen. PMID- 26832795 TI - Induction of miR-137 by Isorhapontigenin (ISO) Directly Targets Sp1 Protein Translation and Mediates Its Anticancer Activity Both In Vitro and In Vivo. AB - Our recent studies found that isorhapontigenin (ISO) showed a significant inhibitory effect on human bladder cancer cell growth, accompanied with cell cycle G0-G1 arrest as well as downregulation of Cyclin D1 expression at transcriptional level via inhibition of Sp1 transactivation in bladder cancer cells. In the current study, the potential ISO inhibition of bladder tumor formation has been explored in a xenograft nude mouse model, and the molecular mechanisms underlying ISO inhibition of Sp1 expression and anticancer activities have been elucidated both in vitro and in vivo. Moreover, the studies demonstrated that ISO treatment induced the expression of miR-137, which in turn suppressed Sp1 protein translation by directly targeting Sp1 mRNA 3'-untranslated region (UTR). Similar to ISO treatment, ectopic expression of miR-137 alone led to G0-G1 cell growth arrest and inhibition of anchorage-independent growth in human bladder cancer cells, which could be completely reversed by overexpression of GFP-Sp1. The inhibition of miR-137 expression attenuated ISO-induced inhibition of Sp1/Cyclin D1 expression, induction of G0-G1 cell growth arrest, and suppression of cell anchorage-independent growth. Taken together, our studies have demonstrated that miR-137 induction by ISO targets Sp1 mRNA 3'-UTR and inhibits Sp1 protein translation, which consequently results in reduction of Cyclin D1 expression, induction of G0-G1 growth arrest, and inhibition of anchorage-independent growth in vitro and in vivo. Our results have provided novel insights into understanding the anticancer activity of ISO in the therapy of human bladder cancer. PMID- 26832798 TI - Dissecting Therapeutic Resistance to ERK Inhibition. AB - The MAPK pathway is frequently activated in many human cancers, particularly melanomas. A single-nucleotide mutation in BRAF resulting in the substitution of glutamic acid for valine (V(600E)) causes constitutive activation of the downstream MAPK pathway. Selective BRAF and MEK inhibitor therapies have demonstrated remarkable antitumor responses in BRAF(V600) (E)-mutant melanoma patients. However, initial tumor shrinkage is transient and the vast majority of patients develop resistance. We previously reported that SCH772984, an ERK 1/2 inhibitor, effectively suppressed MAPK pathway signaling and cell proliferation in BRAF, MEK, and concurrent BRAF/MEK inhibitor-resistant tumor models. ERK inhibitors are currently being evaluated in clinical trials and, in anticipation of the likelihood of clinical resistance, we sought to prospectively model acquired resistance to SCH772984. Our data show that long-term exposure of cells to SCH772984 leads to acquired resistance, attributable to a mutation of glycine to aspartic acid (G(186D)) in the DFG motif of ERK1. Structural and biophysical studies demonstrated specific defects in SCH772984 binding to mutant ERK. Taken together, these studies describe the interaction of SCH772984 with ERK and identify a novel mechanism of ERK inhibitor resistance through mutation of a single residue within the DFG motif. Mol Cancer Ther; 15(4); 548-59. (c)2016 AACR. PMID- 26832800 TI - Write; Copyright. PMID- 26832797 TI - T-Type Ca2+ Channel Inhibition Sensitizes Ovarian Cancer to Carboplatin. AB - Ovarian cancer is the deadliest gynecologic cancer, due in large part to the diagnosis of advanced stage disease, the development of platinum resistance, and inadequate treatment alternatives. Recent studies by our group and others have shown that T-type calcium (Ca(2+)) channels play a reinforcing role in cancer cell proliferation, cell-cycle progression, and apoptosis evasion. Therefore, we investigated whether T-type Ca(2+) channels affect ovarian tumor growth and response to platinum agents. Inhibition of T-type Ca(2+) channels with mibefradil or by silencing expression resulted in growth suppression in ovarian cancer cells with a simultaneous increase in apoptosis, which was accompanied by decreased expression of the antiapoptotic gene survivin (BIRC5). Analysis of intracellular signaling revealed mibefradil reduced AKT phosphorylation, increased the levels and nuclear retention of FOXO transcription factors that repress BIRC5 expression, and decreased the expression of FOXM1, which promotes BIRC5 expression. Combining carboplatin with mibefradil synergistically increased apoptosis in vitro. Importantly, mibefradil rendered platinum-resistant ovarian tumors sensitive to carboplatin in a mouse model of peritoneal metastasis. Together, the data provide rationale for future use of T-type channel antagonists together with platinum agents for the treatment of ovarian cancer. PMID- 26832801 TI - PRP for Arthroscopic Repair of Medium to Large Rotator Cuff Tears: Letter to the Editor. PMID- 26832799 TI - Trastuzumab-Based Photoimmunotherapy Integrated with Viral HER2 Transduction Inhibits Peritoneally Disseminated HER2-Negative Cancer. AB - Peritoneal dissemination is the most frequent metastasis in gastric cancer and is associated with poor prognosis. The lack of particular target antigens in gastric cancer other than HER2 has hampered the development of treatments for peritoneal dissemination of gastric cancer. We hypothesized that HER2-extracellular domain (HER2-ECD) gene transduction combined with trastuzumab-based photoimmunotherapy (PIT) might provide excellent and selective antitumor effects for peritoneal dissemination of gastric cancer. In vitro, adenovirus/HER2-ECD (Ad/HER2-ECD) efficiently transduced HER2-ECD into HER2-negative gastric cancer cells. Trastuzumab-IR700 (Tra-IR700)-mediated PIT induced selective cell death of HER2 ECD-transduced tumor cells. Ad/HER2-ECD also induced homogenous expression of HER2 in heterogeneous gastric cancer cells, resulting in uniform sensitivity of the cells to Tra-IR700-mediated PIT. Anti-HER2 PIT integrated with adenoviral HER2-ECD gene transfer was applied in mice bearing peritoneal dissemination of HER2-negative gastric cancer. Intraperitoneal administration of Ad/HER2-ECD and Tra-IR700 with PIT inhibited peritoneal metastasis and prolonged the survival of mice bearing MKN45. Furthermore, minimal side effects allowed the integrated therapy to be used repeatedly, providing better control of peritoneal dissemination. In conclusion, the novel therapy of molecular-targeted PIT integrated with gene transfer technology is a promising approach for the treatment of peritoneal dissemination in gastric cancer. PMID- 26832802 TI - PRP for Arthroscopic Repair of Medium to Large Rotator Cuff Tears: Response. PMID- 26832803 TI - Palliative care reimagined: a needed shift. AB - Palliative care, since its inception over 60 years ago, has set the standard of how to care for people who are dying. Key features among these standards have been the professional development of clinical specialisms such as palliative medicine and palliative nursing; the essential addition of the multidisciplinary team to these two new specialisms that included social, spiritual and allied health workers-an outgrowth of the recognition that routine work with the dying, their carers, and the bereaved required more than solely clinical skills; and the unique partnership with communities that yielded the volunteer movement within palliative care. Professional, evidence-based symptom management and the importance of supportive care in its widest possible sense were and remain the cornerstones of the modern palliative care approach. However, the majority of people with terminal illnesses do not have access to palliative care teams, whose main focus of care remains patients with cancer. In the context outlined above this paper therefore poses two key questions: how can we provide an equitable level of care for all people irrespective of diagnosis and how can we increase the range and quality of non-medical/nursing supportive care in a context of diminishing resources? We argue that an important opportunity and solution can be found by adopting the principles of a public health approach to end-of-life care. PMID- 26832804 TI - Unusual perceptions at the end of life: limitations to the diagnosis of hallucinations in palliative medicine. AB - The diagnosis of hallucination for unusual perceptions such as deathbed visions, near-death experiences, or visions of the bereaved, is unhelpful in palliative medicine both academically and clinically. This paper reviews the broad prevalence data about unusual perceptions in the general population as background to identifying the more narrow epidemiological source from which the much smaller focus on hallucinations seem to emerge. Major debates and limitations of current hallucination research are reviewed to show that current academic and clinical certainties are largely confined to unusual perceptions that can be readily linked to psychopathology, quite specific organic disease states and psychoactive drug use. Current state-of-the-art in hallucination studies does not warrant broad or uncritical use of this type of diagnosis in end-of-life care. Conclusions from interdisciplinary (as opposed to single discipline) hallucination studies suggest that the way forward for clinical and research work in palliative medicine may lie in a more biographical and cultural approach to unusual perceptions at the end of life. PMID- 26832806 TI - Risk prediction for emboli and recurrence of primary cardiac myxomas after resection. AB - BACKGROUND: Risk factors for embolism and recurrence of primary cardiac myxoma are not well established. This study aimed to assess the risk factors for embolism and recurrence of cardiac myxoma, as well as the survival of the patients. METHODS: The medical records of 207 consecutive patients treated for primary cardiac myxoma between September 1988 and October 2014 were retrospectively analyzed. All diagnoses were pathologically confirmed. Data were collected to identify the risk factors influencing the prognosis. RESULTS: Mean age at surgery was 44.2 +/- 15.8 years. Operative mortality (within 30 days of the surgery) occurred in seven patients. Mean follow-up was 9.35 +/- 6.55 years. Embolism occurred in 32 (15.5 %) patients before surgery. Multivariate analysis indicated that small (<= 4.5 cm) myxoma (OR = 5.14; 95 % CI, 2.30-11.94; P < 0.0001) and soft, gelatinous myxoma (OR = 5.84; 95 % CI, 1.91-25.61; P = 0.001) were independently associated with the occurrence of embolism. Ten patients experienced recurrences. After excluding the patients who died within 30 days of surgery, survival was 92.7 % at 10 years. Age, sex, tumor size, cardiopulmonary bypass duration, aortic cross clamp duration, tumor appearance, and pre-operative embolism were not associated with early mortality. Multivariate analysis showed that multicentric myxomas were independently associated with recurrence (OR = 9.45, 95 % CI, 2.15-41.3, P = 0.004). CONCLUSIONS: The surgical resection of primary cardiac myxoma is associated with excellent long-term survival. Tumors <= 4.5 cm and soft tumors were independent risk factors for embolism. Multicentric cardiac myxoma was an independent risk factors for recurrence of myxoma. PMID- 26832807 TI - Treatment of dilated cardiomyopathy in rabbits with mesenchymal stem cell transplantation and platelet-rich plasma. AB - Dilated cardiomyopathy (DCM) is a major cause of cardiovascular mortality and morbidity, and there is evidence to suggest that stem cell transplantation may be a viable treatment option for this condition. Therefore, the goal of the present study was to assess myocardial regeneration in rabbits with doxorubicin-induced DCM treated with adipose mesenchymal stem cells (MSC) alone or in combination with platelet-rich plasma (PRP). Twenty New Zealand rabbits received doxorubicin for the induction of DCM and were divided into four groups according to treatment: saline, MSC, PRP and MSC + RP. Treatment agents were injected directly into the left ventricular myocardium following a thoracoscopy. Rabbits were assessed through echocardiographic and electrocardiographic examinations, as well as serum cardiac troponin I measurements at baseline, after the induction of DCM and 15 days after treatment. Animals were euthanased following the last assessment, and hearts were collected for histopathological analyses. The MSC group showed improvements in all parameters assessed, while the PRP group showed significantly impaired heart function. Histopathology of the heart revealed that the MSC group displayed the lowest number of lesions, while rabbits in the MSC + PRP, saline and PRP groups had steadily advancing lesions. These results suggest that MSC transplantation can improve heart function in rabbits with DCM, and underscore the need for further studies of the effects of PRP on the myocardium. PMID- 26832808 TI - von Frey anesthesiometry to assess sensory impairment after acute spinal cord injury caused by thoracolumbar intervertebral disc extrusion in dogs. AB - Sensory threshold (ST) was measured using an electric von Frey anesthesiometer (VFA) in all limbs of 20 normal dogs and 29 dogs with acute thoracolumbar spinal cord injury (SCI) caused by spontaneous intervertebral disc extrusion. ST values were measured at three separate time points in normal dogs and on days 3, 10 and 30 following decompressive surgery in dogs with SCI. ST values were compared between groups and correlated with locomotor recovery in SCI-affected dogs. ST values were significantly higher (consistent with hypoalgesia) in the pelvic limbs of SCI-affected dogs at day 3, day 10 and day 30 when compared to normal dogs (P <0.05), while no significant difference in thoracic limb ST values was observed between groups. A progressive decrease in pelvic limb ST values occurred in SCI-affected dogs over time, consistent with improvement toward normal sensation or development of allodynia. This finding correlated inversely with locomotor score at 3 and 10 days after surgery. A significant decline in ST values across testing sessions was observed for all limbs of normal and SCI affected dogs and may be related to patient acclimation, operator training effect, or effect of analgesic medications. This study supports the feasibility of VFA to assess differences in ST between normal and SCI-affected dogs. However, future studies must focus on techniques to minimize or compensate for clinical, environmental and behavioral factors which may impact ST values in the clinical setting. PMID- 26832809 TI - Computed tomography and magnetic resonance diagnosis of variations in the anatomical location of the major salivary glands in 1680 dogs and 187 cats. AB - During assessment of routine clinical magnetic resonance imaging (MRI) of the heads of dogs, variations in the location of mandibular and zygomatic salivary glands (SGs) were observed incidentally. The aims of this retrospective study were to describe anatomical variations of the major SGs found on MRI and computed tomography (CT) studies of the head in dogs and cats and to investigate possible clinical relevancy. No anatomical variation of the SGs was seen in cats, but in dogs, although variation of the parotid SG was not identified, that of the mandibular SG was found in 33/1680 animals (2%), either unilaterally (6/33 right sided, 13/33 left-sided) or bilaterally (14/33). The Border terrier breed (19/33, 58%) was over-represented. Each atypically located mandibular SG was positioned medial to the digastric muscle and rostral to the retropharyngeal lymph node. The sublingual glands were difficult to delineate from the mandibular glands. Anatomical variation of one zygomatic gland (3/4 left-sided) was identified in four small-breed dogs (0.2%). Each atypically located zygomatic gland was tilted at the ventrorostral aspect of the masseter muscle underneath the skin surface. MRI and CT characteristics were not different between typically and atypically located SGs. None of the dogs had clinical signs related with SG disease. It was concluded that, with suspected breed predispositions, incidental unilateral or bilateral anatomical variations of mandibular and zygomatic SGs can be encountered in dogs and an awareness of these possible variations may be important in pre-surgical planning. PMID- 26832810 TI - Enhanced antibacterial effect of antibiotics in combination with silver nanoparticles against animal pathogens. AB - Antibiotic resistant bacteria are a serious health risk in both human and veterinary medicine. Several studies have shown that silver nanoparticles (AgNPs) exert a high level of antibacterial activity against antibiotic resistant strains in humans. The aim of this study was to evaluate the antibacterial effects of a combined therapy of AgNPs and antibiotics against veterinary bacteria that show resistance to antibiotics. A microdilution checkerboard method was used to determine the minimal inhibitory concentrations of both types of antimicrobials, alone and in combination. The fractional inhibitory concentration index was calculated and used to classify observed collective antibacterial activity as synergistic, additive (only the sum of separate effects of drugs), indifferent (no effect) or antagonistic. From the 40 performed tests, seven were synergistic, 17 additive and 16 indifferent. None of the tested combinations showed an antagonistic effect. The majority of synergistic effects were observed for combinations of AgNPs given together with gentamicin, but the highest enhancement of antibacterial activity was found with combined therapy together with penicillin G against Actinobacillus pleuropneumoniae. A. pleuropneumoniae and Pasteurella multocida originally resistant to amoxycillin, gentamicin and colistin were sensitive to these antibiotics when combined with AgNPs. The study shows that AgNPs have potential as adjuvants for the treatment of animal bacterial diseases. PMID- 26832811 TI - Infundibula of equine maxillary cheek teeth. Part 1: Development, blood supply and infundibular cementogenesis. AB - There is increasing interest in diseases of infundibula of equine maxillary cheek teeth. Imperfect infundibular cementogenesis has been recognized as an aetiopathological factor for the onset of infundibular necrosis. In this article, infundibular development was examined with particular attention to infundibular blood vessels and cementogenesis. Forty-one deciduous maxillary premolars prior to eruption were investigated using routine histological and immunohistological methods to visualize blood vessels and the enamel organ. Selected specimens were scanned by micro-computed tomography to analyze the three-dimensional configuration of the developing infundibulum. Before eruption, the infundibula are supplied by a central infundibular artery entering the infundibulum from an occlusal direction and by arteries entering the mesial infundibulum from the mesial aspect, and the distal infundibulum from the distal aspect. The central infundibular artery is destroyed shortly after tooth eruption but the lateral arteries remain vital for a time after eruption. As the arteries of the distal infundibulum are located in a more apical position, blood is received for a longer period compared with the mesial infundibulum. Cementogenesis starts first at distinct enamel in-foldings in the occlusal part of the infundibula, advancing in an apical direction. The results suggest a distinct asymmetry between the infundibula with the mesial infundibulum prone to incomplete cementogenesis due to early blood supply cessation. PMID- 26832812 TI - Occlusion of the left anterior descending coronary artery following a negative fractional flow reserve study. Failure or limit of a "gold standard" method? PMID- 26832813 TI - Multipoint pacing of the left ventricle to achieve better resynchronisation and clinical response. PMID- 26832816 TI - Utilization of a Nutrition Support Algorithm Reduces Unnecessary Parenteral Nutrition Use in Pediatric Oncology Inpatients. PMID- 26832815 TI - Affinity and competition for TBP are molecular determinants of gene expression noise. AB - Cell-to-cell variation in gene expression levels (noise) generates phenotypic diversity and is an important phenomenon in evolution, development and disease. TATA-box binding protein (TBP) is an essential factor that is required at virtually every eukaryotic promoter to initiate transcription. While the presence of a TATA-box motif in the promoter has been strongly linked with noise, the molecular mechanism driving this relationship is less well understood. Through an integrated analysis of multiple large-scale data sets, computer simulation and experimental validation in yeast, we provide molecular insights into how noise arises as an emergent property of variable binding affinity of TBP for different promoter sequences, competition between interaction partners to bind the same surface on TBP (to either promote or disrupt transcription initiation) and variable residence times of TBP complexes at a promoter. These determinants may be fine-tuned under different conditions and during evolution to modulate eukaryotic gene expression noise. PMID- 26832817 TI - ADAR1 Suppresses the Activation of Cytosolic RNA-Sensing Signaling Pathways to Protect the Liver from Ischemia/Reperfusion Injury. AB - Excessive inflammation resulting from activation of the innate immune system significantly contributes to ischemia/reperfusion injury (IRI). Inflammatory reactions in both IRI and infections share the same signaling pathways evoked by danger/pathogen associated molecular pattern molecules. The cytosolic retinoid inducible gene I(RIG-I)-like RNA receptor (RLR) RNA sensing pathway mediates type I IFN production during viral infection and the sensing of viral RNA is regulated by adenosine deaminase acting on RNA 1 (ADAR1). Using a model of liver IRI, we provide evidence that ADAR1 also regulates cytosolic RNA-sensing pathways in the setting of ischemic stress. Suppression of ADAR1 significantly enhanced inflammation and liver damage following IRI, which was accompanied by significant increases in type I IFN through cytosolic RNA-sensing pathways. In addition, knocking ADAR1 down in hepatocytes exaggerates inflammatory signaling to dsRNA or endotoxin and results in over production of type I IFN, which could be abolished by the interruption of RIG-I. Therefore, we identified a novel ADAR1-dependent protective contribution through which hepatocytes guard against aberrant cytosolic RLR-RNA-sensing pathway mediated inflammatory reaction in response to acute liver IR. ADAR1 protects against over activation of viral RNA-sensing pathways in non-infectious tissue stress. PMID- 26832818 TI - [Placenta percreta with bladder and rectum invasion]. AB - BACKGROUND: Placenta percreta may lead to massive obstetric haemorrhage, haemodynamic decompensation, and ultimately death. Total obstetric hysterectomy is universally accepted as treatment; however, the emergence of new techniques such as the uterine artery angioembolisation approach, and the use of chemotherapy agents such as methotrexate, are alternatives also described in the literature. CLINICAL CASE: A 28 year-old patient, in her fourth gestation, with a previous history of 2 vaginal and 1 caesarean birth 4, in her 28.4 week of pregnancy, by second trimester ultrasound, was diagnosed with placenta percreta with bladder and rectal invasion using magnetic resonance imaging. Multidisciplinary and sequential treatment included: Caesarean with placenta in situ, uterine artery embolisation immediately after caesarean, chemotherapy with methotrexate weekly for 4 doses, and finally obstetric hysterectomy after bilateral hypogastric artery ligation. The outcome was favourable and the patient was discharged in good general condition. CONCLUSIONS: The protocoled and sequential management including selective embolization immediately after caesarean section with placenta in situ, weekly chemotherapy with methotrexate and obstetric hysterectomy, preceded by bilateral ligation of the hypogastric arteries, is a therapeutic alternative to be considered in cases of placenta percreta. PMID- 26832819 TI - Non-ionic macroporous polystyrene adsorbents for removal of serum toxins in liver failure by hemoperfusion. AB - Strong base anion exchange resin (e.g., BL-300) is currently used to eliminate bilirubin from blood in clinical hemoperfusion. However, there is a potential weakness of the resin to remove heparin and activation of coagulation. To overcome this weakness, we prepared a novel non-ionic macroporous polystyrene adsorbent (SZ-9) with rich mesopores and high surface area by suspension polymerization. Test results indicated that SZ-9 performed better adsorption capacity for bilirubin than BL-300. In addition, better blood compatibility was observed during whole blood hemoperfusion. Therefore, adsorbent SZ-9 might be an efficient alternative to anion exchange resin for the removal of bilirubin in hemoperfusion. PMID- 26832820 TI - Cracking the Glycome Encoder: Signaling, Trafficking, and Glycosylation. AB - The glycoproteome, the ensemble of glycans and their carrier proteins, plays major roles in multicellular life by regulating cell interactions with their environment. How information is encoded into the glycome, in other words how glycosylation is modulated in response to signals, remains largely unclear. Glycosylation enzymes operate predominantly in the endoplasmic reticulum (ER) and Golgi, a highly compartmentalized membrane-bound environment. Recent work indicates that this compartmentalization is plastic and tightly regulated. For instance, specific signals can induce the relocation of O-glycosylation enzymes, GALNTs, from the Golgi to the ER, resulting in significant upregulation of O glycosylation initiation. We have named this re-compartmentation process the 'GALA pathway'. GALA illustrates how membrane trafficking in the secretory pathway can regulate protein glycosylation and thus encode information in the glycome. PMID- 26832822 TI - An Unexpected Controlled New Oxidant: SO4(.-). AB - A controlled new oxidant sulfate radical anion (SO4(.-)) was found and it can be easily prepared by mixing Na2S2O4 and TBHP with stirring. In this new metal-free oxidation system (Na2S2O4/TBHP), SO4(.-) can be used as a controllable oxidant to oxidize various aromatic alcohols to the corresponding aldehydes in good yields without any acid formation at room temperature. SO4(.-) was determined by a DMPO (5,5-dimethyl-1-pyrroline-N-oxide) spin-trapping EPR method at room temperature on a Bruker E500 spectrometer and the results suggested that SO4(.-) was generated in this transformation. PMID- 26832821 TI - Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding. AB - Plasmodium falciparum exports proteins into erythrocytes using the Plasmodium export element (PEXEL) motif, which is cleaved in the endoplasmic reticulum (ER) by plasmepsin V (PMV). A recent study reported that phosphatidylinositol-3 phosphate (PI(3)P) concentrated in the ER binds to PEXEL motifs and is required for export independent of PMV, and that PEXEL motifs are functionally interchangeable with RxLR motifs of oomycete effectors. Here we show that the PEXEL does not bind PI(3)P, and that this lipid is not concentrated in the ER. We find that RxLR motifs cannot mediate export in P. falciparum. Parasites expressing a mutated version of KAHRP, with the PEXEL motif repositioned near the signal sequence, prevented PMV cleavage. This mutant possessed the putative PI(3)P-binding residues but is not exported. Reinstatement of PEXEL to its original location restores processing by PMV and export. These results challenge the PI(3)P hypothesis and provide evidence that PEXEL position is conserved for co-translational processing and export. PMID- 26832823 TI - ELAKCA: Enzyme-Linked Aptamer Kissing Complex Assay as a Small Molecule Sensing Platform. AB - We report herein a novel sandwich-type enzyme-linked assay for the "signal-on" colorimetric detection of small molecules. The approach (referred to as enzyme linked aptamer kissing complex assay (ELAKCA)) relied on the kissing complex based recognition of the target-bound hairpin aptamer conformational state by a specific RNA hairpin probe. The aptamer was covalently immobilized on a microplate well surface to act as target capture element. Upon small analyte addition, the folded aptamer was able to bind to the biotinylated RNA hairpin module through loop-loop interaction. The formed ternary complex was then revealed by the introduction of the streptavidin-horseradish peroxidase conjugate that catalytically converted the 3,3',5,5'-tetramethylbenzidine substrate into a colorimetric product. ELAKCA was successfully designed for two different systems allowing detecting the adenosine and theophylline molecules. The potential practical applicability in terms of biological sample analysis (human plasma), temporal stability, and reusability was also reported. Owing to the variety of both hairpin functional nucleic acids, kissing motifs, and enzyme-based signaling systems, ELAKCA opens up new prospects for developing small molecule sensing platforms of wide applications. PMID- 26832824 TI - Rational optimization of amber suppressor tRNAs toward efficient incorporation of a non-natural amino acid into protein in a eukaryotic wheat germ extract. AB - Amber suppression is a useful method of genetically incorporating a non-natural amino acid (NAA) into a protein during translation by utilizing an NAA-charged amber suppressor tRNA (sup-tRNA). A wheat germ extract (WGE) is suitable for this method by virtue of its high productivity and versatility in addition to its advantages as a cell-free translation system. However, in spite of this high potential, a genetic NAA incorporation system in WGE has not been sufficiently optimized in terms of sup-tRNAs, in contrast to that in E. coli and its cell extracts. We herein rationally optimized amber sup-tRNAs to efficiently incorporate a model NAA, p-acetyl-phenylalanine (AcPhe), into a protein in WGE, via flexizyme-based aminoacylation. The optimized sup-tRNA (named tLys-opt) that was pre-charged with AcPhe exclusively yielded up to 220 MUg mL(-1) of AcPhe incorporated protein (yellow fluorescent protein, YPet) under the optimal conditions. This high productivity is comparable to the best reported yield of a similar NAA-incorporated protein synthesized with an engineered aminoacyl-tRNA synthetase/sup-tRNA pair in WGE, despite the fact that tLys-opt that has released AcPhe was not reused at all in this study. The results clearly show both the necessity of optimizing sup-tRNAs for efficient NAA incorporation and the validity of our strategy for their optimization. Because the optimization strategy described here is expected to be applicable not only to amber sup-tRNAs for other NAAs but also to ones used in other acylation methods, it would facilitate the synthesis of large amounts of various types of NAA-incorporated proteins in WGE. PMID- 26832825 TI - One-Pot Biosynthesis of High-Concentration alpha-Glucose 1-Phosphate from Starch by Sequential Addition of Three Hyperthermophilic Enzymes. AB - alpha-Glucose 1-phosphate (G1P) is synthesized from 5% (w/v) corn starch and 1 M phosphate mediated by alpha-glucan phosphorylase (alphaGP) from the thermophilic bacterium Thermotoga maritima at pH 7.2 and 70 degrees C. To increase G1P yield from corn starch containing branched amylopectin, a hyper-thermostable isoamylase from Sulfolobus tokodaii was added for simultaneous starch gelatinization and starch-debranching hydrolysis at 85 degrees C and pH 5.5 before alphaGP use. The pretreatment of isoamylase increased G1P titer from 120 mM to 170 mM. To increase maltose and maltotriose utilization, the third thermostable enzyme, 4 glucanotransferase (4GT) from Thermococcus litoralis, was added during the late stage of G1P biotransformation, further increasing G1P titer to 200 mM. This titer is the highest G1P level obtained on starch or its derived products (maltodextrin and soluble starch). This study suggests that in vitro multienzyme biotransformation has an advantage of great engineering flexibility in terms of space and time compared with microbial fermentation. PMID- 26832826 TI - [Effects of lidocaine and esmolol infusions on hemodynamic changes, analgesic requirement, and recovery in laparoscopic cholecystectomy operations]. AB - OBJECTIVE: We compared the effects of lidocaine and esmolol infusions on intraoperative hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery in laparoscopic cholecystectomy surgery. METHODS: The first group (n=30) received IV lidocaine infusions at a rate of 1.5mg/kg/min and the second group (n=30) received IV esmolol infusions at a rate of 1mg/kg/min. Hemodynamic changes, intraoperative and postoperative analgesic requirements, and recovery characteristics were evaluated. RESULTS: In the lidocaine group, systolic arterial blood pressures values were lower after the induction of anesthesia and at 20min following surgical incision (p<0.05). Awakening time was shorter in the esmolol group (p<0.001); Ramsay Sedation Scale scores at 10min after extubation were lower in the esmolol group (p<0.05). The modified Aldrete scores at all measurement time points during the recovery period were relatively lower in the lidocaine group (p<0.05). The time to attain a modified Aldrete score of >=9 points was prolonged in the lidocaine group (p<0.01). Postoperative resting and dynamic VAS scores were higher in the lidocaine group at 10 and 20min after extubation (p<0.05, p<0.01, respectively). Analgesic supplements were less frequently required in the lidocaine group (p<0.01). CONCLUSION: In laparoscopic cholecystectomies, lidocaine infusion had superiorities over esmolol infusions regarding the suppression of responses to tracheal extubation and postoperative need for additional analgesic agents in the long run, while esmolol was more advantageous with respect to rapid recovery from anesthesia, attenuation of early postoperative pain, and modified Aldrete recovery (MAR) scores and time to reach MAR score of 9 points. PMID- 26832827 TI - [Comparison of the postoperative analgesic effects of naproxen sodium and naproxen sodium-codeine phosphate for arthroscopic meniscus surgery]. AB - BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used to control arthroscopic pain. Addition of oral effective opioid "codeine" to NSAIDs may be more effective and decrease parenteral opioid consumption in the postoperative period. The aim of this study was to compare the efficacy and side effects of naproxen sodium and a new preparation naproxen sodium-codeine phosphate when administered preemptively for arthroscopic meniscectomy. METHODS: Sixty-one patients were randomized into two groups to receive either oral naproxen sodium (Group N) or naproxen sodium-codeine phosphate (Group NC) before surgery. The surgery was carried out under general anesthesia. Intravenous meperidine was initiated by patient-controlled analgesia (PCA) for all patients. The primary outcome measure was pain score at the first postoperative hour assessed by the Visual Analogue Scale (VAS). Sedation assessed by Ramsey Sedation Scale, first demand time of PCA, postoperative meperidine consumption, side effects and hemodynamic data were also recorded. RESULTS: The groups were demographically comparable. Median VAS scores both at rest and on movement were significantly lower in Group NC compared with Group N, except 18(th) hour on movement (p<0.05). The median time to the first demand of PCA was shorter in Group N compared with Group NC (p<0.001). Meperidine consumption was higher in Group N compared with Group NC (p<0.001). There was no difference between groups with respect to side effects (p>0.05). CONCLUSIONS: The combination of naproxen sodium-codeine phosphate provided more effective analgesia than naproxen sodium and did not increase side effects. PMID- 26832828 TI - Voice Changes after Late Recurrent Laryngeal Nerve Identification Thyroidectomy. AB - OBJECTIVES: To assess voice changes in patients after thyroidectomy where the recurrent laryngeal nerve (RLN) was found late in the thyroid dissection and where the RLN was not injured (late RLN identification technique). METHODS: This study was conducted on 64 patients who underwent thyroidectomy by late RLN identification technique. Voice was assessed preoperatively, 1 week, 3 months, and 6 months after surgery using the voice assessment protocol and Voice Problem Self-Assessment Scale. The study group was divided into two subgroups (hemithyroidectomy: N = 13 and total thyroidectomy: N = 51). Voice assessments of both subgroups were then compared with a control group (N = 20) of patients who recently underwent extracervical surgeries. RESULTS: All voice analysis differences between the control group and the individual study subgroup were nonsignificant. Dysphonia in the study group was significantly worse at 1 week and 3 months postoperatively but became nonsignificant at 6 months postoperatively. The deviations from the preoperative acoustic analysis were significant only in the first week postoperative comparison for fundamental frequency, noise-to-harmonic ratio, and maximal phonation time and thereafter became nonsignificant. Significant Voice Problem Self-Assessment Scale mean score increase (worsening) was also detected only at first week postoperatively. CONCLUSION: Minimal voice changes were reported early after late RLN identification thyroidectomy in absence of RLN injury and disappeared gradually in a few months. Those changes are comparable with that of other extracervical surgeries, making thyroidectomy with late RLN identification a relatively safe technique as regard voice. PMID- 26832829 TI - Chemical Changes in Nonthermal Plasma-Treated N-Acetylcysteine (NAC) Solution and Their Contribution to Bacterial Inactivation. AB - In continuation of our previous reports on the broad-spectrum antimicrobial activity of atmospheric non-thermal dielectric barrier discharge (DBD) plasma treated N-Acetylcysteine (NAC) solution against planktonic and biofilm forms of different multidrug resistant microorganisms, we present here the chemical changes that mediate inactivation of Escherichia coli. In this study, the mechanism and products of the chemical reactions in plasma-treated NAC solution are shown. UV-visible spectrometry, FT-IR, NMR, and colorimetric assays were utilized for chemical characterization of plasma treated NAC solution. The characterization results were correlated with the antimicrobial assays using determined chemical species in solution in order to confirm the major species that are responsible for antimicrobial inactivation. Our results have revealed that plasma treatment of NAC solution creates predominantly reactive nitrogen species versus reactive oxygen species, and the generated peroxynitrite is responsible for significant bacterial inactivation. PMID- 26832831 TI - Diminished oligomerization in the synthesis of new anti-angiogenic cyclic peptide using solution instead of solid-phase cyclization. AB - The design and synthesis of novel peptides that inhibit angiogenesis is an important area for anti-angiogenic drug development. Cyclic and small peptides present several advantages for therapeutic application, including stability, solubility, increased bio-availability and lack of immune response in the host cell. We describe here the synthesis and biological evaluations of a new cyclic peptide analog of CBO-P11: cyclo(RIKPHE), designated herein as CBO-P23M, a hexamer peptide encompassing residues 82 to 86 of VEGF which are involved in the interaction with VEGF receptor-2. CBO-P23M was prepared using in solution cyclization, therefore reducing the peptide cyclodimerization occurred during solid-phase cyclization. The cyclic dimer of CBO-P23M, which was obtained as the main side product during synthesis of the corresponding monomer, was also isolated and investigated. Both peptides markedly reduce VEGF-A-induced phosphorylation of VEGFR-2 and Erk1/2. Moreover, they exhibit anti-angiogenic activity in an in vitro morphogenesis study. Therefore CBO-P23M and CBO-P23M dimer appear as attractive candidates for the development of novel angiogenesis inhibitors for the treatment of cancer and other angiogenesis-related diseases. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 368-375, 2016. PMID- 26832830 TI - Post-floral Erection of Stalks Provides Insight into the Evolution of Fruit Orientation and Its Effects on Seed Dispersal. AB - That stalks reorient after flowering to face upwards is a common phenomenon in many flowering plants, indicating the potential importance of fruit orientation on seed dispersal. But this idea has not been subject to an empirical test. We examined this hypothesis by analysing the evolutionary correlation between fruit orientation and other characters and by investigating the effects of fruit orientation on seed dispersal. We found that 1) in a sub-alpine plant community, upward fruit orientation strongly correlates with fruits that act as seed containers, which are often of dry type and are dispersed by non-animal vectors; 2) as exemplified by the Campanulaceae s. str., fruit orientation strongly correlates with dehiscence position. Upwardly-oriented capsules dehisce at the apex, whereas pendent ones dehisce at the base, in both cases ensuring that seeds are released from an upright position; 3) in manipulation experiments on Silene chungtienensis, upward fruits (the natural state) exhibit much greater dispersal distances and more dispersive pattern than pendent ones, and have a more even distribution of dispersal direction than horizontal ones. Our results suggest that fruit orientation may have important function in seed dispersal, which may be the reason why the phenomenon that stalk erection after flowering occurs widely. PMID- 26832832 TI - The Pathogenesis of Implant-Related Reactive Lesions: A Clinical, Histologic and Polarized Light Microscopy Study. AB - BACKGROUND: Peri-implant soft tissue reactive lesions (I-RLs) may jeopardize implant success and survival. To the best of the authors' knowledge, its pathogenesis is unknown. The objective of this study is to conduct a clinicopathologic and polarized light microscopy (PLM) analysis of 14 new I-RLs and compare them with comparable tooth-associated cases (T-RLs) to better understand I-RL pathogenesis. METHODS: Fifty-eight new cases of I-RL and T-RL were retrieved from the pathology department archives of Rambam Health Care Campus, Haifa, Israel. Retrospective analysis of histopathologic and clinical features was conducted, documented, and then compared for: 1) I-RL (n = 14), 2) peri-implant pyogenic granuloma (I-PG) (n = 5), 3) peri-implant peripheral giant cell granuloma (I-PGCG) (n = 9), 4) T-RL (n = 44), 5) tooth-associated pyogenic granuloma (T-PG) (n = 21), and 6) tooth-associated peripheral giant cell granuloma (T-PGCG) (n = 23). Presence of foreign bodies was assessed using PLM. RESULTS: Foreign bodies were found more commonly in I-RLs (n = 13/14; 93%) when compared with T-RLs (n = 18/44; 41%), which was a statistically significant difference (P = 0.01) with an odds ratio of 7.9. Microscopically, I-PGCG was associated with: 1) lower multinucleated giant cell count (P = 0.04); 2) lower density of mesenchymal cells (P = 0.05); and 3) more diffuse, non-lobulated stromal morphology (P = 0.001). Clinically, I-RLs were found in patients who were older, and all cases were located in the posterior region: mandible (n = 12/14; 86%) and maxilla (n = 2/14; 14%). CONCLUSIONS: In cases of implant failure, implantation of foreign bodies may play a role with subsequent development of I PG and I-PGCG-like lesions. Clinicians should be aware of this risk so they can implement measures to minimize adverse implant outcomes. PMID- 26832833 TI - Effects of Melatonin on Oxidative Stress Index and Alveolar Bone Loss in Diabetic Rats With Periodontitis. AB - BACKGROUND: The aim of this study is to evaluate the effects of systemic melatonin treatment on serum oxidative stress index (OSI) and alveolar bone loss (ABL) in rats with diabetes mellitus (DM) and periodontitis. METHODS: Seventy Sprague Dawley rats were divided into control, experimentally induced periodontitis (EP), DM, EP-DM, EP and melatonin treatment (EP-MEL), DM and melatonin treatment (DMMEL), and EP-DM-MEL groups. DM was induced by alloxan, after which periodontitis was induced by ligature for 4 weeks. After removal of the ligature, the rats in the melatonin groups (EP-MEL, DM-MEL, and EP-DM-MEL) were treated with a single dose of melatonin (10 mg/body weight) every day for 14 consecutive days. At the end of the study, all of the rats were euthanized, and intracardiac blood samples and mandible tissues were obtained for biochemical and histologic analyses. Serum levels of total oxidant status/total antioxidant status and OSI were measured. In addition, neutrophil and osteoclast densities and myeloperoxidase activities were determined in gingival tissue homogenates, and ABL was evaluated with histometric measurements. RESULTS: Melatonin treatment significantly reduced fasting plasma glucose levels in the rats with DM. In addition, reduced OSI and ABL levels were detected in the EP-MEL and DM-MEL groups; the reductions in the EP-DM-MEL group were found to be more prominent. Melatonin also significantly decreased the increased myeloperoxidase activities and osteoclast and neutrophil densities in the EP, DM, and EP-DM groups. CONCLUSION: It is revealed in this experimental study that melatonin significantly inhibited hyperglycemia-induced oxidative stress and ABL through antiDM and antioxidant effects in rats with DM and periodontitis. PMID- 26832834 TI - A Prospective, Case-Controlled Study Evaluating the Use of Enamel Matrix Derivative on Human Buccal Recession Defects: A Human Histologic Examination. AB - BACKGROUND: Connective tissue grafts (CTGs) and coronally advanced flaps (CAFs) do not regenerate periodontal attachment apparatus when used to treat gingival recessions (GRs). Instead of generating new bone, cementum, and inserting periodontal ligament fibers, CTG+CAF repairs through a long epithelial junction and connective tissue attachment. Enamel matrix derivatives (EMDs) have demonstrated proof-of-principle that periodontal regeneration can be achieved, although data are limited. METHODS: Three patients, each requiring extraction of four premolars before orthodontic treatment, were enrolled in a randomized, open label study. Two months after induction of Miller Class I and II GR, each patient received EMD+CAF for three teeth and CTG+CAF for one tooth for root coverage. Nine months after root coverage, all four premolars from each of the three patients were surgically extracted en bloc for histologic and microcomputed tomography (micro-CT) analysis, looking for evidence of periodontal regeneration. Standard clinical measurements, radiographs, and intraoral photographs were taken over prescribed time points. RESULTS: Seven of the nine teeth treated with EMD+CAF demonstrated varying degrees of periodontal regeneration, detailed through histology with new bone, cementum, and inserting fibers. Micro-CT corroborated these findings. None of the three teeth treated with CTG+CAF showed periodontal regeneration. Clinical measurements were comparable for both treatments. One instance of root resorption and ankylosis was noted with EMD+CAF. CONCLUSIONS: EMD+CAF continues to show histologic evidence of periodontal regeneration via human histology, this being the largest study (nine teeth) examining its effect when treating GR. The mechanism of action, ideal patient profile, and criteria leading to predictable regeneration are in need of further exploration. PMID- 26832835 TI - State-related differences in the level of psychomotor activity in patients with bipolar disorder - Continuous heart rate and movement monitoring. AB - Measuring changes in psychomotor activity is a potential tool in the monitoring of the course of affective states in bipolar disorder. Previous studies have been cross-sectional and only some have used objective measures. The aim was to investigate state-related differences in objectively-measured psychomotor activity in bipolar disorder. During a 12 weeks study, repeated measurements of heart rate and movement monitoring over several days were collected during different affective states from 19 outpatients with bipolar disorder. Outcomes included activity energy expenditure (AEE) and trunk acceleration (ACC). Symptoms were clinically assessed using Hamilton Depression Rating Scale (HDRS-17) and Young Mania Rating Scale (YMRS). Compared to patients in a euthymic state, patients in a manic state had significantly higher AEE. Compared to patients in a depressive state, patients in a manic state had significantly higher ACC and AEE. There was a significant diurnal variation in ACC and AEE between affective states. Finally, there was a significant correlation between the severity of manic symptoms and ACC and AEE, respectively. This first study measuring psychomotor activity during different affective states using a combined heart rate and movement sensor supports that psychomotor activity is a core symptom in bipolar disorder that is altered during affective states. PMID- 26832836 TI - Factors associated with illicit drugs' lifetime and frequent/heavy use among students results from a population survey. AB - Substance use among teenage students and factors associated were investigated through a survey using a questionnaire adapted from the WHO's Program on Research and Reporting on the Epidemiology of Drug Dependence, additional questions on family factors and personal risks, and the Coopersmith Self-Esteem Inventory, adapted to Brazil. The target population consisted of 3891 10-22-year-old students from the city of Embu das Artes, Sao Paulo, Brazil. The prevalence of lifetime substance use was 26.7%. Most commonly used substances were energy drinks combined with alcohol (19%), solvents (11.2%) and marijuana (4.8%). Almost 60% of the students had already tried alcohol and 18.2% had tried tobacco. Factors associated to lifetime substance use were: lower self-esteem, going to nightclubs at least twice a week, use of alcohol, trying tobacco, bad relationship with the mother, permissive mothers, practicing sports as an obligation, working, and higher socioeconomic level. Concerning frequent/heavy substance use, chances were found to be higher among students who had use tobacco and alcohol, going to nightclubs at least twice a week, and those with lower self esteem. Preventive actions concerning drug use should focus on avoiding the first experimentation, approaching family relationships, and improving students' self esteem. PMID- 26832837 TI - Pathways from victimization to substance use: Post traumatic stress disorder as a mediator. AB - Traumatic events are linked with an array of adverse consequences such as substance use. Only a few individuals exposed to traumatic events, however, suffer from post traumatic stress disorder (PTSD) or substance use. The present longitudinal study examined the inter-relationship among victimization, PTSD, and substance use. 674 participants (53% African Americans, 47% Puerto Ricans) were surveyed over five time waves at mean ages 14, 19, 24, 29, and 36. Of the 674, 60% were females. We used Mplus to perform structural equation modeling. Victimization at ages 19, 24, and 29 was directly associated with substance use at age 36 and was also related to PTSD at age 36. PTSD, in turn, was related to substance use at age 36. This study indicates the importance of intervention for those who have been victimized with a focus on PTSD treatment. From a public health perspective, health providers should consider treatment and prevention programs for helping individuals cope with some of the consequences of victimization. This might ultimately reduce substance use. PMID- 26832838 TI - Human X-linked Intellectual Disability Factor CUL4B Is Required for Post-meiotic Sperm Development and Male Fertility. AB - In this study, we demonstrate that an E3-ubiquitin ligase associated with human X linked intellectual disability, CUL4B, plays a crucial role in post-meiotic sperm development. Initially, Cul4b(Delta)/Y male mice were found to be sterile and exhibited a progressive loss in germ cells, thereby leading to oligoasthenospermia. Adult Cul4b mutant epididymides also contained very low numbers of mature spermatozoa, and these spermatazoa exhibited pronounced morphological abnormalities. In post-meiotic spermatids, CUL4B was dynamically expressed and mitosis of spermatogonia and meiosis of spermatocytes both appeared unaffected. However, the spermatids exhibited significantly higher levels of apoptosis during spermiogenesis, particularly during the acrosome phase through the cap phase. Comparative proteomic analyses identified a large-scale shift between wild-type and Cul4b mutant testes during early post-meiotic sperm development. Ultrastructural pathology studies further detected aberrant acrosomes in spermatids and nuclear morphology. The protein levels of both canonical and non-canonical histones were also affected in an early spermatid stage in the absence of Cul4b. Thus, X-linked CUL4B appears to play a critical role in acrosomal formation, nuclear condensation, and in regulating histone dynamics during haploid male germ cell differentiation in relation to male fertility in mice. Thus, it is possible that CUL4B-selective substrates are required for post-meiotic sperm morphogenesis. PMID- 26832839 TI - Development of Liposomal Formulation for Delivering Anticancer Drug to Breast Cancer Stem-Cell-Like Cells and its Pharmacokinetics in an Animal Model. AB - The objective of the present study is to develop a liposomal formulation for delivering anticancer drug to breast cancer stem-cell-like cells, ANV-1, and evaluate its pharmacokinetics in an animal model. The anticancer drug ESC8 was used in dexamethasone (Dex)-associated liposome (DX) to form ESC8-entrapped liposome named DXE. ANV-1 cells showed high-level expression of NRP-1. To enhance tumor regression, we additionally adapted to codeliver the NRP-1 shRNA-encoded plasmid using the established DXE liposome. In vivo efficacy of DXE-NRP-1 was carried out in mice bearing ANV-1 cells as xenograft tumors and the extent of tumor growth inhibition was evaluated by tumor-size measurement. A significant difference in tumor volume started to reveal between DXE-NRP-1 group and DXE Control group. DXE-NRP-1 group showed ~4 folds and ~2.5 folds smaller tumor volume than exhibited by untreated and DXE-Control-treated groups, respectively. DXE disposition was evaluated in Sprague-Dawley rats following an intraperitoneal dose (3.67 mg/kg of ESC8 in DXE). The plasma concentrations of ESC8 in the DXE formulation were measured by liquid chromatography mass spectrometry and pharmacokinetic parameters were determined using a noncompartmental analysis. ESC8 had a half-life of 11.01 +/- 0.29 h, clearance of 2.10 +/- 3.63 L/kg/h, and volume of distribution of 33.42 +/- 0.83 L/kg. This suggests that the DXE liposome formulation could be administered once or twice daily for therapeutic efficacy. In overall, we developed a potent liposomal formulation with favorable pharmacokinetic and tumor regressing profile that could sensitize and kill highly aggressive and drug-resistive cancer stem-cell-like cells. PMID- 26832841 TI - Antibiotic Utilization and Opportunities for Stewardship Among Hospitalized Patients With Influenza Respiratory Tract Infection. AB - OBJECTIVE: Hospitalized influenza patients are often treated with antibiotics empirically while awaiting final diagnosis. The goal of this study was to describe the inappropriate continuation of antibiotics for influenza respiratory tract infections (RTIs). DESIGN: We retrospectively studied adults admitted to our institution over 2 respiratory flu seasons with positive influenza RTIs. Inappropriate antibiotic duration (IAD) was defined as antibiotic use for >24 hours after a positive influenza test in patients presenting with <72 hours of RTI symptoms and with no other indications of bacterial infection. RESULTS: During the study period, 322 patients included in this study were admitted for influenza RTI. Respiratory cultures were ordered for 50 of these patients (15.5%) and 71 patients (22%) had a positive chest x-ray, but antibiotics were prescribed to 211 patients (65.5%) on admission. Antibiotics were inappropriately continued in 73 patients (34.5%). Patients receiving IAD had a longer length of stay (LOS) (median, 6 days; range, 4-9 days) compared with those whose antibiotics were discontinued appropriately (median, 5 days; range, 3-8 days) and those who were not treated with antibiotics (median, 4 days; range, 3-6 days; P<.001). However, mortality was similar among these 3 groups: 3 patients (4.1%) from the IAD cohort died; 6 patients (4.3%) from the group with an appropriate antibiotic duration died; and 2 patients [1.8%] from the group given no antibiotics died (P=.510). The 30-day readmission rates were similar as well: 9 patients (12.3%) from the IAD group were readmitted within 30 days; 21 patients (15.2%) from the group with appropriate antibiotic duration were readmitted; and 11 patients (9.9%) from the group given no antibiotics were readmitted (P=.455). Total hospital costs were greater in patients treated with IAD ($10,645; range, $6,485-$18,035) compared with the group treated with appropriate antibiotic duration ($7,479; range, $4,866-$12,922) and the group given no antibiotics $5,961 (range, $4,711-$9,575). Thus, the hospital experienced a median loss in net hospital revenue of $2,076 per IAD patient compared with a patient for which antibiotic duration was appropriate. CONCLUSION: The majority of patients with influenza RTI received antibiotics on admission, and 34.5% were inappropriately continued on antibiotics without evidence of bacterial infection, which led to increased LOS, loss of net revenue, and no improvement in outcome. Thus, stewardship initiatives aimed at this population are warranted. PMID- 26832842 TI - Rapid aberration measurement with pixelated detectors. AB - Aberration-corrected microscopy in a scanning transmission electron microscope requires the fast and accurate measurement of lens aberrations to align or 'tune' the corrector. Here, we demonstrate a method to measure aberrations based on acquiring a 4D data set on a pixelated detector. Our method is compared to existing procedures and the choice of experimental parameters is examined. The accuracy is similar to existing methods, but in principle this procedure can be performed in a few seconds and extended to arbitrary order. This method allows rapid measurement of aberrations and represents a step towards more automated electron microscopy. PMID- 26832840 TI - Small interfering RNAs from bidirectional transcripts of GhMML3_A12 regulate cotton fiber development. AB - Natural antisense transcripts (NATs) are commonly observed in eukaryotic genomes, but only a limited number of such genes have been identified as being involved in gene regulation in plants. In this research, we investigated the function of small RNA derived from a NAT in fiber cell development. Using a map-based cloning strategy for the first time in tetraploid cotton, we cloned a naked seed mutant gene (N1 ) encoding a MYBMIXTA-like transcription factor 3 (MML3)/GhMYB25-like in chromosome A12, GhMML3_A12, that is associated with fuzz fiber development. The extremely low expression of GhMML3_A12 in N1 is associated with NAT production, driven by its 3' antisense promoter, as indicated by the promoter-driven histochemical staining assay. In addition, small RNA deep sequencing analysis suggested that the bidirectional transcriptions of GhMML3_A12 form double stranded RNAs and generate 21-22 nt small RNAs. Therefore, in a fiber-specific manner, small RNA derived from the GhMML3_A12 locus can mediate GhMML3_A12 mRNA self-cleavage and result in the production of naked seeds followed by lint fiber inhibition in N1 plants. The present research reports the first observation of gene-mediated NATs and siRNA directly controlling fiber development in cotton. PMID- 26832843 TI - Prevalence of metabolic syndrome as per the NCEP and IDF definitions vis-a-vis severity and duration of psoriasis in a semi-urban Maharashtrian population: A case control study. AB - BACKGROUND: The inexorable inflammation in patients of psoriasis predisposes to various disorders, notably, a cluster of cardiovascular and metabolic abnormalities christened 'metabolic syndrome'. AIM: To assess the prevalence of metabolic syndrome and its correlation with the severity and duration of psoriasis. METHODS: One hundred psoriasis patients and 100 age-and-sex matched controls were included, whose waist circumference and blood pressure were measured; fasting serum cholesterol, triglycerides and glucose levels quantified; disease severity assessed and metabolic syndrome defined separately by two globally accepted criteria. RESULTS: Metabolic syndrome (38%:12%), hypertriglyceridemia (53%:25%), impaired glucose tolerance (38%:16%) [P<0.001] and low HDL (P=0.002) were significantly more prevalent in cases as compared to controls as were the mean values of triglycerides and fasting blood sugar. Increased mean age of psoriasis patients and duration of disease strongly correlated with the presence of this syndrome. The divergence in definition of the syndrome by two separate criteria was also highly significant (P<0.001). CONCLUSION: Metabolic syndrome had significant presence in and increased with the duration but remained unaffected by the severity of psoriasis in our study patients. PMID- 26832844 TI - Birt-Hogg-Dube syndrome and colon polyps. PMID- 26832845 TI - [Hyperparathyroidism in patients with stones. Influence of deficit 25-OH vitamin D]. PMID- 26832846 TI - Quantitative fragment analysis of FLT3-ITD efficiently identifying poor prognostic group with high mutant allele burden or long ITD length. AB - Mutation of the fms-like tyrosine kinase 3-internal tandem duplication (FLT3 ITD), which is one of the most frequent genetic alterations, strongly contributes to an increased risk of treatment failure and to poor prognosis. In this study, we established quantitative fragment analysis of FLT3-ITD simultaneously measuring mutant allele burden and length, verified the analytical performance and evaluated the clinical significance in adult acute myeloid leukemia (AML) patients. FLT3-ITD was detected in 73 of 363 adult AML patients (20.1%) and high mutant allelic burden (?50%, n=13) and long ITD length (?70 base pairs, n=15) were significantly associated with inferior overall survival (OS; P=0.002 and 0.005, respectively) and event-free survival (EFS; P=0.004 and 0.007, respectively). FLT3-ITD poor prognostic group was identified as patients with high allele burden or long ITD length (n=24), which revealed significant adverse clinical outcome for both OS (P<0.001) and EFS (P<0.001). In cytogenetically normal AML, even FLT3-ITD low allele burden and short length was associated with poorer OS (P=0.037) and EFS (P=0.044) than wild type, whose influence was overcome when hematopoietic stem cell transplantation was performed. In minimal residual disease monitoring, FLT3-ITD negativity after consolidation therapy was a valuable predictor of better OS (P<0.001) and EFS (P<0.001). FLT3-ITD poor prognostic group with high mutant allele burden or long ITD length is efficiently identified by quantitative fragment analysis. PMID- 26832849 TI - Core-shell nanoparticles by silica coating of metal oxides in a dual-stage hydrothermal flow reactor. AB - gamma-Fe2O3@SiO2, TiO2@SiO2, and alpha-Fe2O3@SiO2 core-shell nanoparticles were synthesized by a surfactant-free hydrothermal method in a continuous flow dual stage reactor. Uniform silica shells of 2 nm thickness were obtained when grown on gamma-Fe2O3 and TiO2 nanoparticles while thicker and more irregular shells were deposited on alpha-Fe2O3 due to low pH. PMID- 26832848 TI - Favorable clinical outcome and unique characteristics in association with Twist1 overexpression in de novo acute myeloid leukemia. AB - Epithelial-mesenchymal transition (EMT) is a critical process for inducing stem like properties of epithelial cancer cells. However, the role of EMT inducers in hematological malignancies is unknown. Twist1, an EMT inducer necessary for cell migration, has recently been found to have transcriptionally regulatory activity on the expression of Bmi1, and these two are capable of promoting tumorigenesis in a synergized manner. Knowing that Bmi1 expression is essential for maintenance of leukemic stem cells, we speculate that Twist1 might govern the pathogenesis of acute myeloid leukemia (AML) development as well. We found that upregulated Twist1 increased Bmi1 expression in AML and endued leukemic cells a higher proliferative potential and increased resistance to apoptosis. In primary AML samples, there was strong positive correlation between the expression levels of Twist1 and Bmi1. AML patients whose leukemic blasts harbored overexpressed Twist1 had a more aggressive clinical phenotype, but they were more likely to have a better clinical outcome after standard therapy. In vitro studies confirmed that Twist1-overexpressing leukemic cells were more susceptible to cytarabine, but not daunorubicin, cytotoxicity. Our findings suggest that, in a subset of AML patients, Twist1 has a prominent role in the pathogenesis of the disease that leads to unique clinical phenotypes. PMID- 26832847 TI - Rationale for revision and proposed changes of the WHO diagnostic criteria for polycythemia vera, essential thrombocythemia and primary myelofibrosis. AB - The 2001/2008 World Health Organization (WHO)-based diagnostic criteria for polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) were recently revised to accomodate new information on disease-specific mutations and underscore distinguishing morphologic features. In this context, it seems to be reasonable to compare first major diagnostic criteria of the former WHO classifications for myeloproliferative neoplasm (MPN) and then to focus on details that have been discussed and will be proposed for the upcoming revision of diagnostic guidelines. In PV, a characteristic bone marrow (BM) morphology was added as one of three major diagnostic criteria, which allowed lowering of the hemoglobin/hematocrit threshold for diagnosis, which is another major criterion, to 16.5 g/dl/49% in men and 16 g/dl/48% in women. The presence of a JAK2 mutation remains the third major diagnostic criterion in PV. Subnormal serum erythropoietin level is now the only minor criterion in PV and is used to capture JAK2-unmutated cases. In ET and PMF, mutations that are considered to confirm clonality and specific diagnosis now include CALR, in addition to JAK2 and MPL. Also in the 2015 discussed revision, overtly fibrotic PMF is clearly distinguished from early/prefibrotic PMF and each PMF variant now includes a separate list of diagnostic criteria. The main rationale for these changes was to enhance the distinction between so-called masked PV and JAK2-mutated ET and between ET and prefibrotic early PMF. The proposed changes also underscore the complementary role, as well as limitations of mutation analysis in morphologic diagnosis. On the other hand, discovery of new biological markers may probably be expected in the future to enhance discrimination of the different MPN subtypes in accordance with the histological BM patterns and corresponding clinical features. PMID- 26832850 TI - Gene expression and proteomic analysis of shoot apical meristem transition from dormancy to activation in Cunninghamia lanceolata (Lamb.) Hook. AB - In contrast to annual plants, in perennial plants, the shoot apical meristem (SAM) can undergo seasonal transitions between dormancy and activity; understanding this transition is crucial for understanding growth in perennial plants. However, little is known about the molecular mechanisms of SAM development in trees. Here, light and transmission electron microscopy revealed that evident changes in starch granules, lipid bodies, and cell walls thickness of the SAM in C. lanceolata during the transition from dormancy to activation. HPLC-ESI-MS/MS analysis showed that levels of indole-3-acetic acid (IAA) increased and levels of abscisic acid (ABA) decreased from dormant to active stage. Examination of 20 genes and 132 differentially expressed proteins revealed that the expression of genes and proteins potentially involved in cell division and expansion significantly increased in the active stage, whereas those related to the abscisic acid insensitive 3(ABI3), the cytoskeleton and energy metabolism decreased in the dormant stage. These findings provide new insights into the complex mechanism of gene and protein expression and their relation to cytological and physiological changes of SAM in this coniferous species. PMID- 26832852 TI - Impact of chemical peeling combined with negative pressure on human skin. AB - OBJECTIVE: In vivo changes in skin barrier function after chemical peeling with alpha hydroxyacids (AHAs) have been previously reported. However, the additional effects of physical treatment with chemical agents on skin barrier function have not been adequately studied. This study measured the degree of acute skin damage and the time required for skin barrier repair using non-invasive bioengineering methods in vivo with human skin to investigate the additional effect of a 4% AHA chemical jet accelerated at supersonic velocities. METHODS: Thirteen female subjects (average age: 29.54 +/- 4.86 years) participated in this study. The faces of the subjects were divided into half according to the block randomization design and were then assigned to receive AHA peeling alone or AHA peeling combined with pneumatic pressure on each side of the face. Transepidermal water loss (TEWL), skin colour and skin blood flow were evaluated at baseline and at 30 min, 2, 5 and 7 days after treatment. RESULTS: The TEWL and skin blood flow were significantly increased after 30 min in chemodermabrasion compared with chemical peeling alone (P < 0.05). The TEWL and skin blood flow recovered to baseline after 2 days, and TEWL was significantly decreased at 7 days compared with chemical peeling alone (P < 0.05). CONCLUSIONS: Chemodermabrasion can temporarily impair skin barriers, but it is estimated that it can enhance the skin barrier function after 7 days compared to the use of a chemical agent alone. In addition, chemodermabrasion has a more effective impact in the dermis and relatively preserves the skin barrier. PMID- 26832853 TI - [Emergency contraception and conscientious objection: an ongoing debate]. PMID- 26832854 TI - [Graduates' opinions on the utility of training in gerontology]. PMID- 26832851 TI - Facets of Subjective Health From Early Adulthood to Old Age. AB - OBJECTIVE: Subjective health is a complex indicator predicting longevity independent of objective health. Few studies examine genetic and environmental mechanisms underlying different facets of subjective health across the life course. METHOD: Three subjective health measures were examined in 12,900 twins ( Mage = 63.38, range = 25-102) from nine studies in the Interplay of Genes and Environment across Multiple Studies Consortium: self-rated health (SRH), health compared with others (COMP), and health interfering with activities (ACT). RESULTS: Analyses indicated age and sex differences in mean scores depending on the measure. SRH and ACT showed significant linear and non-linear moderation by age for individual differences in both genetic and environmental variance. Significant sex differences in components of variance were found for SRH and ACT, but not COMP. DISCUSSION: Subjective health appears to be dependent on frame of reference and reflect different aspects of health. Results suggest different genetic and environmental mechanisms underlie each facet. PMID- 26832855 TI - [Hospital detention in tuberculosis control]. AB - This article describes the actions of public health services of the city of Barcelona to prevent tuberculosis transmission by noncompliant smear-positive patients by using the possibilities of Spanish Law 3/1986. The actions were based on a resolution of the health authorities on the need to locate such patients and to detain them in hospitals to provide treatment. This involved police cooperation, informing noncompliant patients, and requesting ratification from the Administrative Court. The article describes the process and the characteristics of the cases involved. Over nine years, from July 2006 to June 2015, the law was used in only twelve cases. The authors conclude that the criteria of prudence and proportionality were used in the application of the law, which resulted in the treatment of patients who posed a risk to their environment, reducing the transmission of infection. PMID- 26832856 TI - [Gender differences in Peruvian researchers according to Google Scholar, 2015]. PMID- 26832857 TI - [Chronic diseases as a priority for the public health surveillance system in Spain]. AB - At present, epidemiological surveillance in Spain remains focused on the communicable diseases included in the list of notifiable diseases. However, there has been a change in epidemiological pattern that predominated until the last few decades of the twentieth century. Infectious diseases, which used to be the leading causes of morbidity and mortality, have given way to a predominance of chronic diseases. In this regard, progress has been made in the drafting and adoption of specific legal regulations on public health monitoring. However, Spain has yet to develop this legislation which, among other elements, includes the mandate to organize the surveillance of non-communicable diseases in Spain. This article aims to describe some points that should be considered in the development of a national surveillance system linked to existing strategies for the prevention and control of chronic diseases. PMID- 26832858 TI - A pilot study to determine the diagnostic criteria of spiculated masses for BI RADS MRI category 5: when to perform re-biopsy after discordant pathologic result? AB - BACKGROUND: This study aimed to investigate (1) the MRI and clinical findings useful to differentiate malignant from benign spiculated masses and (2) the diagnostic criteria of spiculated masses for BI-RADS MRI category 5, for which any non-malignant biopsy result is considered discordant and a re-biopsy is recommended. MATERIALS AND METHODS: Spiculated breast masses, depicted by 3.0/1.5 T contrast-enhanced MRI between June 2008 and March 2014, were retrospectively analyzed. Patient's age, lesion size, minimum/average apparent diffusion coefficient values (ADCmin/ADCave), and BI-RADS descriptors were compared between malignant and benign lesions. Based on these results, we assessed criteria to define category 5 spiculated masses with a >=95 % probability of malignancy and evaluated their diagnostic performance. RESULTS: A total of 140 lesions (Malignant group, n = 131; Benign group, n = 9) were analyzed. Patient's age, lesion size, ADCmin and ADCave showed significant differences between the two groups, while none of the BI-RADS descriptors, including kinetic curve assessment, showed any significant difference in frequency. Multivariate logistic regression analysis demonstrated that patient's age and lesion size were the significant predictive factors of malignancy. Of all the assessed criteria for category 5 spiculated masses, "age >50 years or size >9 mm, or both" were selected as the best criteria to minimize the possibility of unnecessary re biopsies and inappropriate follow-up for malignancies. CONCLUSIONS: Patient's age and lesion size are useful to differentiate malignant from benign spiculated breast masses. In cases with non-malignant biopsy results, spiculated masses with "age >50 years or size >9 mm, or both" are more likely malignant. PMID- 26832859 TI - Impact of young age on local control after partial breast irradiation in Japanese patients with early stage breast cancer. AB - BACKGROUND: Partial breast irradiation (PBI) is an alternative to whole breast irradiation (WBI) for breast-conserving therapy (BCT). A randomised phase 3 trial demonstrated that PBI using multicatheter brachytherapy had an equivalent rate of local recurrence, disease-free survival, and overall survival as compared to WBI. However, limited data are available on PBI efficacy for young patients with breast cancer. METHODS: We evaluated consecutive patients with Tis-2 (<= 3 cm) N0 1 breast cancer who underwent BCT. For PBI, patients received radiotherapy using multicatheter brachytherapy in an accelerated manner with a dose of 32 Gy in eight fractions over 5-6 days. For WBI, patients received an external beam radiation therapy that was applied to the entire breast with a total dose of 50 Gy in fractions of 2 Gy for 5 weeks. Two hundred seventy-four patients with 278 lesions received PBI; 190 patients with 193 lesions received WBI. RESULTS: Patients aged <50 years including 98 women with 99 lesions receiving PBI and 85 women with 85 lesions receiving WBI were selected. Ipsilateral breast tumor recurrence rate was 3.0 and 2.4 % by PBI and WBI, respectively (P = 0.99). There was no significant difference in 4-year probability of disease-free survival (97.6 and 91.4 % for PBI and WBI, respectively; P = 0.87). CONCLUSIONS: This is the first report of PBI efficacy in young patients in Asia. Although it is a nonrandomized retrospective chart review of a small cohort of patients with a relatively short follow-up period, PBI may be a better option than WBI following BCS in some young patients with breast cancer. PMID- 26832860 TI - Characterizing Hospital Admissions to a Tertiary Care Hospital After Typhoon Haiyan. AB - OBJECTIVE: On November 8, 2013, Typhoon Haiyan (Yolanda) made landfall in the Philippines. The literature characterizing the medical, surgical, and obstetrics burden following typhoons is lacking. This study aimed to improve disaster preparedness by analyzing medical diagnoses presenting to a city district hospital before, during, and after Typhoon Haiyan. METHODS: The assessment of disease burden and trends was based on logbooks from a local hospital and a nongovernmental organization field hospital for the medicine, surgical, and obstetrics wards before, during, and after the typhoon. RESULTS: The hospital provided no services several days after typhoon impact, but there was an overall increase in patient admissions once the hospital reopened. An increase in gastroenteritis, pneumonia, tuberculosis, and motor vehicle collision-related injuries was seen during the impact phase. A dengue fever outbreak occurred during the post-impact phase. There was a noticeable shift in a greater percentage of emergent surgical cases performed versus elective cases during the impact and post-impact phases. CONCLUSION: Overall, several public health measures can prevent the increase in illnesses seen after a disaster. To prepare for the nonfatal burden of disease after a typhoon, health care facilities should increase their resources to accommodate the surge in patient volume. PMID- 26832861 TI - Composition of phosphorus in wetland soils determined by SMT and solution 31P-NMR analyses. AB - In Eastern China, wetlands are common in the lower reaches of catchments or in coastal zones. Wetlands are at risk from eutrophication because of the large quantities of phosphorus (P) they receive from rivers. They are also decreasing in size. In this contribution, we present information about the composition of P in wetland soils, obtained using the Standards, Measurements, and Testing (SMT) protocol and (31)P-nuclear magnetic resonance (NMR) spectroscopy. Average P concentrations varied in the different wetland soils and, in four of the five wetlands sampled, exceeded 500 mg?kg(-1). HCl-inorganic P (Pi) was the main Pi fraction in wetland soils. The percentage contribution of Pi (89.7 %) to total P was the highest in the Yangtze River estuary wetland. Six P components were detected by (31)P-NMR analysis. Mono-P was the main organic P (Po) in wetland soils. Orthophosphate (Ortho-P) was positively and negatively related to NaOH-Pi (R (2) = 0.957, p < 0.001) and HCl-Pi (R (2) = -0.689, p < 0.001), respectively. Orthophosphate monoesters (Mono-P) were positively related to Po (R (2) = 0.617, p < 0.001) and ortho-P (R (2) = 0.624, p < 0.001), respectively. The main Po component was Mono-P, and it may be mineralized to ortho-P under the frequently changing redox conditions in wetland soils. The information from this study will support the development of robust scientific and effective policy for P management in wetlands. PMID- 26832862 TI - Evaluation of an extraction method for a mixture of endocrine disrupters in sediment using chemical and in vitro biological analyses. AB - Aquatic sediments are contaminated by a wide diversity of organic pollutants such as endocrine-disrupting chemicals (EDCs) which encompass a broad range of chemical classes having natural and anthropogenic origins. The use of in vitro bioassays is now widely accepted as an alternative method for their detection in complex samples. However, based on the diversity of EDC chemical properties, their common extraction is difficult and comprehensive validation of extraction methods for a bioanalysis purpose is still weakly documented. In this study, we compared the performance of several organic solvents, i.e., acetone, methanol, dichloromethane, heptane, dichloromethane/acetone (50:50, v/v), dichloromethane/methanol (50:50, v/v), heptane/acetone (50:50, v/v), and heptane/methanol (50:50, v/v), to extract a diversity of active chemicals from a spiked sediment matrix using pressurized liquid extraction. For this purpose, we defined a mixture of 12 EDCs with a wide range of polarity (2 < log Kow < 8) (i.e., estrone, 17beta-estradiol, bisphenol A, o,p'DDT, 4-tert-octylphenol, fenofibrate, triphenyl phosphate, clotrimazole, PCB-126, 2,3,7,8 TCDD, benzo[k]fluoranthene, and dibenzo[a,h]anthracene). Working concentrations of each individual compound in the mixture were determined as equipotent concentrations on the basis of the concentration-addition (CA) model applied to in vitro estrogenic, dioxin-like, and pregnane X receptor (PXR)-like activities. Extraction efficiencies based on both chemical and biological analyses were assessed in triplicate in artificial blank sediment spiked with this mixture and in natural sediment contaminated by native EDCs. In both spiked and natural sediment, MeOH/DCM yields the best recovery while heptane was the least efficient solvent. Our study provided the validation of a sediment extraction methodology for EDC bioanalysis purposes, which can be used for comprehensive environmental contamination characterization. PMID- 26832863 TI - Impact of fresh tailing deposition on the evolution of groundwater hydrogeochemistry at the abandoned Manitou mine site, Quebec, Canada. AB - The abandoned Manitou mine site has produced acid mine drainage (AMD) for several decades. In order to limit the detrimental environmental impacts of AMD, different rehabilitation scenarios were proposed and analyzed. The selected rehabilitation scenario was to use fresh tailings from the neighboring Goldex gold mine as monolayer cover and to maintain an elevated water table. In order to assess the impact of the Goldex tailing deposition on the hydrogeochemistry of the Manitou mine site, a network of 30 piezometers was installed. These piezometers were used for continuous measurement of the groundwater level, as well as for water sampling campaigns for chemical quality monitoring, over a 3 year period. Hydrochemical data were analyzed using principal component analysis. Results clearly showed the benefic impact of fresh tailing deposition on the groundwater quality around the contaminated area. These findings were also confirmed by the evolution of electrical conductivity. In addition to the improvement of the physicochemical quality of water on the Manitou mine site, new tailing deposition induced an increase of water table level. However, at this time, the Manitou reactive tailings are not completely submerged and possible oxidation might still occur, especially after ceasing of the fresh tailing deposition. Therefore, complementary rehabilitation scenarios should still be considered. PMID- 26832864 TI - Naphthalene degradation by catalytic ozonation based on nickel oxide: study of the ethanol as cosolvent. AB - Naphthalene (NA) is a polycyclic aromatic hydrocarbon with toxic properties in aquatic systems. Ozonation (O3) and catalytic ozonation (O3-cat) processes are attractive alternatives of degradation for this kind of compound. NA (20 mg L-1) degradation by conventional and catalytic ozonation in the presence of a cosolvent (ethanol) was the aim of this study. This solution was proposed to simulate some aspects of real wastewaters where not only water acts as solvent. Two proportions of the mixture ethanol/water were selected (30:70 and 50:50) with the purpose of studying the cosolvent effect on NA degradation system by ozonation. O3-cat process used nickel oxide as catalyst (0.1 g L-1). The degradation analysis of NA by O3-cat in two different proportions of cosolvent showed that in the case of 30:70 (ethanol/water), a 95 % of NA elimination in 60 min was obtained, while in the case 50:50 (ethanol/water), only 55 % was achieved. The O3 process showed similar results of degradation to the initial compound in comparison with catalytic system. According to these results, there is an inhibition effect in pollutant removal by ethanol due to the higher ethanol concentration; the lower elimination rate of NA was obtained (by 40 % during the 60 min). The by-products analysis of ozonation process detected oxalic and formic acids. Treatments with NiO presented less production of organic acids in comparison with conventional ozonation process. The high concentration of ethanol has a relevant factor in the elimination of NA and formation of organic acids; samples with 50 % of cosolvent have showed a higher concentration of organic acids. X-ray photoelectron spectroscopy (XPS) study of O3-cat of diluent (O3-NiO control) and O3-NA-NiO showed the presence of -CO3 absorbed on catalyst due to ethanol decomposition. PMID- 26832865 TI - Effects of iron-aluminium oxides and organic carbon on aggregate stability of bauxite residues. AB - In order to successfully establish vegetation on bauxite residue, properties such as aggregate structure and stability require improvement. Spontaneous plant colonization on the deposits in Central China over the last 20 years has revealed that natural processes may improve the physical condition of bauxite residues. Samples from three different stacking ages were selected to determine aggregate formation and stability and its relationship with iron-aluminium oxides and organic carbon. The residue aggregate particles became coarser in both dry and wet sieving processes. The mean weight diameter (MWD) and geometry mean diameter (GMD) increased significantly, and the proportion of aggregate destruction (PAD) decreased. Natural stacking processes could increase aggregate stability and erosion resistant of bauxite residues. Free iron oxides and amorphous aluminium oxides were the major forms in bauxite residues, but there was no significant correlation between the iron-aluminium oxides and aggregate stability. Aromatic C, alkanes-C, aliphatic-C and alkenes-C were the major functional groups present in the residues. With increasing stacking age, total organic carbon content and aggregate-associated organic carbon both increased. Alkanes-C, aliphatic-C and alkenes-C increased and were mainly distributed in macro-aggregates, whereas aromatic-C was mainly distributed in <0.05-mm aggregates. Organic carbon stability in micro-aggregates was higher than that in macro-aggregates and became more stable. Organic carbon contents in total residues, and within different aggregate sizes, were all negatively correlated with PAD. It indicated that organic materials had a more significant effect on macro-aggregate stability and the effects of iron-aluminium oxides maybe more important for stability of micro aggregates. PMID- 26832866 TI - Concentrations and health risk assessment of metal(loid)s in indoor dust from two typical cities of China. AB - Eleven trace metal(loid)s were determined in the household dust samples from Chengdu and Tianjin, China, and related human exposure and health risk to metal(loid)s via indoor dust intake were evaluated. The trace metal(loid)s were found to be highly concentrated and polluted in the indoor environment of Chengdu and Tianjin, especially for Cu, Zn, Cd, Sb, and Pb, of which the enrichment factors exceeding 5. Metal(loid) levels in the indoor dust samples exhibited no statistical differences between the two cities, with the exception of Sb, which was detected higher in the Chengdu samples. Bioaccessibilities in stomach phase of each element were estimated, Cd, Pb, and Sr exhibited higher bioaccessibility, and Sb showed the lowest bioaccessibility in both Chengdu and Tianjin. Dust ingestion was the main metal(loid) exposure pathway for Chengdu and Tianjin inhabitants, followed by dermal contact, dust inhalation accounted for less than 1 % of the total daily metal(loid) intakes and thus could be negligible. Children suffered more risk when exposure to metal(loid)s via indoor dust intake due to their higher frequency of hand to mouth activities. Risk evaluation indicated that, for most Chengdu and Tianjin inhabitants, there is little non-cancer and carcinogen risk when exposure to indoor dust. However, there is a potential non cancer and carcinogen risk for children and adults in Chengdu, in the case of highly exposed scenario based on the current study. PMID- 26832867 TI - Agricultural runoff pollution control by a grassed swales coupled with wetland detention ponds system: a case study in Taihu Basin, China. AB - The performance of a field grassed swales (GSs) coupled with wetland detention ponds (WDPs) system was monitored under four typical rainfall events to assess its effectiveness on agricultural runoff pollution control in Taihu Basin, China. The results indicated that suspended solids (SS) derived from the flush process has significant influence on pollution loads in agricultural runoff. Determination of first flush effect (FFE) indicated that total suspended solids (TSS) and total phosphorus (TP) exhibited moderate FFE, while chemical oxygen demand (COD) and total nitrogen (TN) showed weak FFE. Average removal efficiencies of 83.5 +/- 4.5, 65.3 +/- 6.8, 91.6 +/- 3.8, and 81.3 +/- 5.8 % for TSS, COD, TN, and TP were achieved, respectively. The GSs played an important role in removing TSS and TP and acted as a pre-treatment process to prevent clogging of the subsequent WDPs. Particle size distributions (PSDs) analysis indicated that coarse particles larger than 75 MUm accounted for 80 % by weight of the total particles in the runoff. GSs can effectively reduce coarse particles (>=75 MUm) in runoff, while its removal efficiency for fine particles (<75 MUm) was low, even minus results being recorded, especially for particles smaller than 25 MUm. The length of GSs is a key factor in its performance. The WDPs can remove particles of all sizes by sedimentation. In addition, WDPs can improve water quality due to their buffering and dilution capacity during rainfall as well as their water purification ability during dry periods. Overall, the ecological system of GSs coupled with WDPs is an effective system for agricultural runoff pollution control. PMID- 26832868 TI - Study on wastewater toxicity using ToxTrakTM method. AB - ToxTrakTM method is an analytical tool for the measurement of toxicity of drinking water, wastewater and natural water. It is based upon the estimation of the inhibitive effect on bacterial respiration processes. The main aim of this work was to test the applicability of ToxTrakTM method in the assessment of wastewater toxicity in a full-scale WWTP in Poland. In order to achieve it, the study was divided into two parts. First, the validation of ToxTrakTM method was performed. Second, wastewater toxicity was monitored in the long- and short-term campaigns. Validation of ToxTrakTM method revealed that the indigenous biomass (mixed cultures of activated sludge microorganisms) was more sensitive than Escherichia coli for both materials (wastewater and phenol) tested. The values of degree of inhibition determined for phenol towards indigenous biomass and E. coli were close to each other, and no statistically significant difference between them was found. It confirmed the reliability of the results obtained with the help of ToxTrakTM test. The toxicity of the effluent was always lower than that of the influent and the linear correlation between them was found. Despite, the decrease of wastewater toxicity in the WWTP, the effluents were ranked as toxic or highly toxic according to the classification of wastewater based upon the acute toxicity. PMID- 26832869 TI - Bioturbation effects on heavy metals fluxes from sediment treated with activated carbon. AB - Adding activated carbon (AC) to sediment has been proposed as an in situ sediment remediation technique. To date, it is not clear whether this technique is effective in the treatment of heavy metal-contaminated sediment in the presence of bioturbators. In the present study, we compare the ability of granular activated carbon (GAC) and powder-activated carbon (PAC) to reduce Cu, Zn, and Pb pore water concentrations at environmentally relevant concentrations in the absence and presence of Chironomid larvae. Compared to untreated sediment, PAC and GAC addition in the absence of Chironomid larvae resulted in reductions of free Cu concentrations of 78 and 66 % just below the sediment-water interface after 28 days, respectively. While for Pb and Zn these concentration reductions were only 40 and 38, 19 and 25 %, respectively. The presence of Chironomid larvae in untreated, and GAC sediment generally increased the free heavy metals concentrations in pore water, especially in the deeper layers. In comparison with untreated sediment, the coexistence of AC enhanced the accumulation of heavy metals, especially for PAC. This increased bioaccumulation may decrease the survival of Chironomid larvae. The result indicated that ACs may not be suitable for the remediation of heavy metal-contaminated sediments. PMID- 26832870 TI - Distribution, speciation, environmental risk, and source identification of heavy metals in surface sediments from the karst aquatic environment of the Lijiang River, Southwest China. AB - The distribution and speciation of several heavy metals, i.e., As, Cd, Cr, Cu, Hg, Pb, and Zn, in surface sediments from the karst aquatic environment of the Lijiang River, Southwest China, were studied comparatively. The mean contents of Cd, Cu, Hg, Pb, and Zn were 1.72, 38.07, 0.18, 51.54, and 142.16 mg/kg, respectively, which were about 1.5-6 times higher than their corresponding regional sediment background values. Metal speciation obtained by the optimized BCR protocol highlighted the bioavailable threats of Cd, Cu, and Zn, which were highly associated with the exchangeable fraction (the labile phase). Hierarchical cluster analysis indicated that in sediments, As and Cr were mainly derived from natural and industrial sources, whereas fertilizer application might lead to the elevated level of Cd. Besides, Cu, Hg, Pb, and Zn were related to traffic activities. The effects-based sediment quality guidelines (SQGs) showed that Hg, Pb, and Zn could pose occasional adverse effects on sediment-dwelling organisms. However, based on the potential ecological risk assessment (PER) and risk assessment code (RAC), Cd was the most outstanding pollutant and posed the highest ecological hazard and bioavailable risk among the selected metals. Moreover, the metal partitioning between water and sediments was quantified through the calculation of the pseudo-partitioning coefficient (K P), and result implied that the sediments in this karst aquatic environment cannot be used as stable repositories for the metal pollutants. PMID- 26832871 TI - Trichoderma longibrachiatum Evx1 is a fungal biocatalyst suitable for the remediation of soils contaminated with diesel fuel and polycyclic aromatic hydrocarbons. AB - Trichoderma sp. strain Evx1 was isolated from a semi-deciduous forest soil in Southern Italy. It decolorizes polynuclear organic dyes and tolerates high concentrations of phenanthrene, anthracene, fluoranthene, and pyrene. The ability of this ascomycete fungus to degrade polycyclic aromatic hydrocarbons was verified in vitro and confirmed by its strong phenoloxidase activity in the presence of gallic acid. Phylogenetic characterization of Trichoderma sp. Evx1 positioned this strain within the species Trichoderma longibrachiatum. The potential use of this species for the bioremediation of contaminated environmental matrices was tested by inoculating diesel-spiked soil with a dense mycelial suspension. The biodegradation percentage of the C12-40 hydrocarbon fraction in the inoculated soil rose to 54.2 +/- 1.6 %, much higher than that in non-inoculated soil or soil managed solely by a combination of watering and aeration. The survival and persistence of T. longibrachiatum Evx1 throughout the bioremediation trial was monitored by PCR-DGGE analysis. The fungal strain was still present in the soil 30 days after bioaugmentation. These findings indicate that T. longibrachiatum Evx1 may be a suitable inoculum in bioremediation protocols for the reclamation of soils contaminated by complex mixtures of hydrocarbons. PMID- 26832872 TI - Persistence of pentolite (PETN and TNT) in soil microcosms and microbial enrichment cultures. AB - Pentolite is a mixture (1:1) of 2,4,6-trinitrotoluene (TNT) and pentaerythritol tetranitrate (PETN), and little is known about its fate in the environment. This study was aimed to determine the dissipation of pentolite in soils under laboratory conditions. Microcosm experiments conducted with two soils demonstrated that dissipation rate of PETN was significantly slower than that of TNT. Interestingly, the dissipation of PETN was enhanced by the presence of TNT, while PETN did not enhanced the dissipation of TNT. Pentolite dissipation rate was significantly faster under biostimulation treatment (addition of carbon source) in soil from the artificial wetland, while no such stimulation was observed in soil from detonation field. In addition, the dissipation rate of TNT and PETN in soil from artificial wetland under biostimulation was significantly faster than the equivalent abiotic control, although it seems that non-biological processes might also be important for the dissipation of TNT and PETN. Transformation of PETN was also slower during establishment of enrichment culture using pentolite as the sole nitrogen source. In addition, transformation of these explosives was gradually reduced and practically stopped after the forth cultures transfer (80 days). DGGE analysis of bacterial communities from these cultures indicates that all consortia were dominated by bacteria from the order Burkholderiales and Rhodanobacter. In conclusion, our results suggest that PETN might be more persistent than TNT. PMID- 26832873 TI - Economic assessment of different mulches in conventional and water-saving rice production systems. AB - Water-saving rice production systems including alternate wetting and drying (AWD) and aerobic rice (AR) are being increasingly adopted by growers due to global water crises. Application of natural and artificial mulches may further improve water economy of water-saving rice production systems. Conventionally flooded rice (CFR) system has been rarely compared with AWD and AR in terms of economic returns. In this 2-year field study, we compared CFR with AWD and AR (with and without straw and plastic mulches) for the cost of production and economic benefits. Results indicated that CFR had a higher production cost than AWD and AR. However, application of mulches increased the cost of production of AWD and AR production systems where plastic mulch was expensive than straw mulch. Although the mulching increased the cost of production for AWD and AR, the gross income of these systems was also improved significantly. The gross income from mulched plots of AWD and AR was higher than non-mulched plots of the same systems. In conclusion, AWD and AR effectively reduce cost of production by economizing the water use. However, the use of natural and artificial mulches in such water-saving environments further increased the economic returns. The maximized economic returns by using straw mulch in water-saving rice production systems definitely have pragmatic implications for sustainable agriculture. PMID- 26832875 TI - A Bayesian-based two-stage inexact optimization method for supporting stream water quality management in the Three Gorges Reservoir region. AB - In this study, a Bayesian-based two-stage inexact optimization (BTIO) method is developed for supporting water quality management through coupling Bayesian analysis with interval two-stage stochastic programming (ITSP). The BTIO method is capable of addressing uncertainties caused by insufficient inputs in water quality model as well as uncertainties expressed as probabilistic distributions and interval numbers. The BTIO method is applied to a real case of water quality management for the Xiangxi River basin in the Three Gorges Reservoir region to seek optimal water quality management schemes under various uncertainties. Interval solutions for production patterns under a range of probabilistic water quality constraints have been generated. Results obtained demonstrate compromises between the system benefit and the system failure risk due to inherent uncertainties that exist in various system components. Moreover, information about pollutant emission is accomplished, which would help managers to adjust production patterns of regional industry and local policies considering interactions of water quality requirement, economic benefit, and industry structure. PMID- 26832874 TI - Reconstruction of historical lead contamination and sources in Lake Hailing, Eastern China: a Pb isotope study. AB - The history records of lead and its stable isotopic ratios were determined in a sediment core to receive anthropogenic impacts on the Lake Hailing in eastern China. The sediment core was dated based on (210)Pb, (137)Cs, and (239+240)Pu. The historical changes of Pb/Al and Pb isotope ratios showed increasing trend upward throughout the core, suggesting changes in energy usage and correlating closely with the experience of a rapid economic and industrial development of the catchment, Linyi City, in eastern China. Based on the mixing end member model of Pb isotope ratios, coal combustion emission dominated anthropogenic Pb sources in the half part of the century contributing 13 to 43 % of total Pb in sediment. Moreover, contributions of chemical and organic fertilizer were 1-13 and 5-14 %, respectively. In contrast, the contribution of leaded gasoline was low than 8 %. The results indicated that historical records of Pb contamination predominantly sourced from coal combustion and chemical and organic fertilizer in the catchment. In addition, an increase of coal combustion source and fertilizers was found throughout the sediment core, whereas the contribution of leaded gasoline had declined after 2000s, which is attributed to the phaseout of leaded gasoline in China. PMID- 26832876 TI - Application of a biosorbent to soil: a potential method for controlling water pollution by pesticides. AB - Different strategies are now being optimized to prevent water from agricultural areas being contaminated by pesticides. The aim of this work was to optimize the adsorption of non-polar (tebuconazole, triadimenol) and polar (cymoxanil, pirimicarb) pesticides by soils after applying the biosorbent spent mushroom substrate (SMS) at different rates. The adsorption isotherms of pesticides by three soils and SMS-amended soils were obtained and the adsorption constants were calculated. The distribution coefficients (K d) increased 1.40-23.1 times (tebuconazole), 1.08-23.7 times (triadimenol), 1.31-42.1 times (cymoxanil), and 0.55-23.8 times (pirimicarb) for soils amended with biosorbent at rates between 2 and 75 %. Increasing the SMS rates led to a constant increase in adsorption efficiency for non-polar pesticides but not for polar pesticides, due to the increase in the organic carbon (OC) content of soils as indicated by K OC values. The OC content of SMS-amended soils accounted for more than 90 % of the adsorption variability of non-polar pesticides, but it accounted for only 56.3 % for polar pesticides. The estimated adsorption of SMS-amended soils determined from the individual adsorption of soils and SMS was more consistent with real experimental values for non-polar pesticides than for polar pesticides. The results revealed the use of SMS as a tool to optimize pesticide adsorption by soils in dealing with specific contamination problems involving these compounds. PMID- 26832877 TI - An ecological risk assessment of pesticides and fish kills in the Sixaola watershed, Costa Rica. AB - Along the southeastern coast of Costa Rica, a variety of pesticides are intensively applied to produce export-quality plantains and bananas. In this region, and in other agricultural areas, fish kills are often documented by local residents and/or in the national news. This study examines principal exposure pathways, measured environmental concentrations, and selected toxicity thresholds of the three most prevalent pesticides (chlorpyrifos, terbufos, and difenoconazole) to construct a deterministic risk assessment for fish mortality. Comparisons of observed pesticide concentrations, along with estimated biological effects and observations during actual fish kills, highlight gaps in knowledge in correlating pesticide environmental concentration and toxicity in tropical environments. Observations of fish kill events and measured pesticide concentrations in the field, along with other water quality indicators, suggest that a number of environmental conditions can interact to cause fish mortality and that current species toxicity datasets may not be applicable for estimating toxicological or other synergistic effects, especially in tropical environments. PMID- 26832879 TI - Dielectric barrier discharge plasma induced degradation of aqueous atrazine. AB - Degradation of herbicide atrazine in aqueous solution was investigated using a plate type dielectric barrier discharge (DBD) plasma reactor. DBD plasma was generated at the gas-liquid interface of the formed water film. At discharge time of 14 min, atrazine was degradated effectively with a degradation rate of 99 % at the discharge power of 200 W. The experimental data fitted well with first-order kinetics and the energy efficiency for 90 % degradation of atrazine (G value) was calculated, obtaining a rate constant of 0.35 min(-1) and a G value of 1.27 * 10( 10) mol J(-1) (98.76 mg kW(-1) h(-1)) at a discharge power of 200 W, respectively. The addition of Fe(2+) increased the rate constant and G value dramatically, and a significant decrease of the rate constant and G value was observed with the addition of radical scavengers (tert-butyl alcohol, isopropyl alcohol, or Na2CO3). The generated aqueous O3 and H2O2 were determined, which promoted the degradation of herbicide atrazine. Dechlorination was observed and the experimentally detected Cl(-) was 1.52 mg L(-1) at a discharge time of 14 min. The degradation intermediates of atrazine were detected by means of liquid chromatography-mass spectrometry; dechlorination, hydroxylation, dealkylation, and alkyl oxidation processes were involved in the degradation pathways of atrazine. PMID- 26832878 TI - Current and emerging strategies for organophosphate decontamination: special focus on hyperstable enzymes. AB - Organophosphorus chemicals are highly toxic molecules mainly used as pesticides. Some of them are banned warfare nerve agents. These compounds are covalent inhibitors of acetylcholinesterase, a key enzyme in central and peripheral nervous systems. Numerous approaches, including chemical, physical, and biological decontamination, have been considered for developing decontamination methods against organophosphates (OPs). This work is an overview of both validated and emerging strategies for the protection against OP pollution with special attention to the use of decontaminating enzymes. Considerable efforts have been dedicated during the past decades to the development of efficient OP degrading biocatalysts. Among these, the promising biocatalyst SsoPox isolated from the archaeon Sulfolobus solfataricus is emphasized in the light of recently published results. This hyperthermostable enzyme appears to be particularly attractive for external decontamination purposes with regard to both its catalytic and stability properties. PMID- 26832880 TI - Lymph Node Involvement Pattern and Survival Differences of FIGO IIIC and FIGO IIIA1 Ovarian Cancer Patients After Primary Complete Tumor Debulking Surgery: A 10-Year Retrospective Analysis of the Tumor Bank Ovarian Cancer Network. AB - OBJECTIVE: The main goal of the current study was to compare survival differences among subgroups of primary ovarian cancer patients in International Federation of Gynecology and Obstetrics (FIGO) stages IIIC and IIIA1 after complete tumor debulking surgery. METHODS: A total of 218 patients with primary ovarian cancer who received complete cytoreductive surgery were included in the current retrospective analysis of the validated Tumor Bank Ovarian Cancer Network Database, which covers the periods January 2002 until December 2012. According to their tumor spread pattern, patients were divided into three groups: Group A (peritoneum only), Group B (peritoneum and lymph nodes), and Group C (lymph nodes only). Associations between groups and clinicopathological factors were analyzed using standard statistical procedures. RESULTS: The vast majority of patients were classified into Group B. Lymph node involvement was detected in 70.5 % of the cases where peritoneal implants presented >=2 cm beyond the pelvis (Group A + B). The estimated 5-year overall survival (OS) rates were 47.4 % in Group A, 45.1 % in Group B, and 91.7 % in Group C (p < 0.01). In the subgroup analysis of Group B, both pelvic and para-aortic lymph node involvement was found in 57 % of patients. Patients in Group B who had para-aortic lymph node involvement only had better median progression-free survival (PFS) compared with patients with pelvic lymph node involvement only and pelvic and para-aortic lymph node involvement (28, 16, and 18 months, respectively; p = 0.02). The median OS differed significantly between patients with para-aortic lymph node involvement only versus patients with both pelvic and para-aortic involvement (68.5 vs. 46.7 months; p = 0.02). Three-year PFS was 90.0 % in FIGO IIIA1(i) and 62.6 % in FIGO IIIA1(ii) (hazard ratio 2.30, 95 % confidence interval 0.45-11.58). CONCLUSIONS: Patients with FIGO stage IIIC with lymph node involvement only had the best clinical outcome compared with patients in the same stage with peritoneal involvement only. Furthermore, involvement of both pelvic and para-aortic lymph nodes were of the same infrequency, and involvement of only para-aortic lymph nodes in this stage resulted in a better chance of survival than involvement of pelvic lymph nodes only or both pelvic and para-aortic lymph nodes simultaneously. In accordance with the revised FIGO classification of 2013, our study revealed that FIGO IIIA1(i) is prognostically better compared with FIGO IIIA1(ii). PMID- 26832881 TI - CD133 Expression at the Metastatic Site Predicts Patients' Outcome in Colorectal Cancer with Synchronous Liver Metastasis. AB - BACKGROUND: CD133 is a transmembrane protein that is proposed to be a stem cell marker of colorectal cancer (CRC); however, the correlation between CD133 expression and survival of CRC patients with liver metastasis has not been fully examined. METHODS: CD133 expression was evaluated immunohistochemically, both in primary tumors and synchronous liver metastases of 88 consecutive CRC patients, as well as recurrent lesions in the remnant liver of 27 of these 88 patients. The relationship between CD133 expression and clinicopathological characteristics, recurrence-free survival, and overall survival (OS) was analyzed. RESULTS: CD133 expression in liver metastases (mCD133) was detected in 50 of 88 patients (56.8 %), and had significant correlation with CD133 expression in primary lesions (pCD133) (p < 0.001). CD133 expression in liver recurrent lesions (recCD133) also had a significant correlation with mCD133 (p < 0.001). mCD133+ patients had significantly longer disease-free survival (p = 0.043) and OS (p = 0.014) than mCD133- patients. In addition, mCD133+ patients had a significantly lower rate of extrahepatic recurrence (p < 0.001). CONCLUSIONS: Patients without CD133 expression in liver metastasis had significantly shorter survival, perhaps because mCD133- patients had a significantly higher rate of extrahepatic recurrence. PMID- 26832883 TI - Overexpression of Transmembrane Protein BST2 is Associated with Poor Survival of Patients with Esophageal, Gastric, or Colorectal Cancer. AB - BACKGROUND: Gastrointestinal (GI) cancer, including gastric cancer (GC), colorectal cancer (CRC), and esophageal squamous cell carcinoma (ESCC), is the most common malignancy worldwide. To identify genes that encode transmembrane proteins present in GI cancer, Escherichia coli ampicillin secretion trap libraries were generated from MKN-74 GC cells, and BST2 was identified as overexpressed in GC. This study analyzed the expression and function of the BST2 gene in human GI cancers and examined the relationship between bone marrow stromal antigen-2 (BST-2) expression and GI patient clinicopathologic characteristics. METHODS: Expression and distribution of BST-2 protein was analyzed by immunohistochemistry in 180 GC cases, 140 CRC cases, and 132 ESCC cases. Cell growth was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. RESULTS: Immunohistochemical analysis of BST-2 in GC tissues showed that 65 (36 %) of 180 GC cases were positive for BST 2. Uni- and multivariate analyses demonstrated that BST-2 expression is an independent prognostic classifier of GC patients. Immunohistochemical analysis showed that 46 % of 140 CRC cases and 27 % of 132 ESCC cases were positive for BST-2. In ESCC, BST-2 expression was an independent prognostic predictor for survival. The growth of BST2 small interfering RNA (siRNA)-transfected GC cells was significantly slower than the growth of negative control siRNA-transfected GC cells. The levels of phosphorylated epidermal growth factor receptor, extracellular signal-regulated kinase, and Akt were lower in BST2 siRNA transfected GC cells than in control cells. CONCLUSIONS: The results suggest that BST-2 is involved in tumor progression and serves as an independent prognostic classifier for patients with GC. Because BST-2 is expressed on the cell membrane, BST-2 could be a therapeutic target for GC, CRC, and ESCC. PMID- 26832884 TI - Optimal Surgical Management for Occult Breast Carcinoma: A Meta-analysis. AB - BACKGROUND: Occult breast cancer (OBC) represents a rare clinical entity and poses a therapeutic dilemma. Due to limited experience, no optimal treatment approaches have yet been established. METHODS: A meta-analysis was performed using MEDLINE and EMBASE databases to identify all studies investigating the surgical options for OBC: (1) axillary lymph node dissection (ALND) with radiotherapy (XRT); (2) ALND with mastectomy; and (3) ALND alone. Comparative studies including nonoperative management (observation or XRT alone) were excluded. The primary endpoints were locoregional recurrence, distant metastasis, and mortality rates. RESULTS: The literature search yielded 42 publications. Seven studies met the inclusion criteria comprising 241 patients. Among these patients, 94 (39 %) underwent ALND with XRT, 112 (46.5 %) underwent mastectomy, and 35 (14.5 %) underwent ALND alone. Mean follow-up was 61.8 +/- 16.2 months (range 5-396 months). Locoregional recurrence (12.7 vs. 9.8 %), distant metastasis (7.2 vs. 12.7 %), and mortality rates (9.5 vs. 17.9 %) were similar between ALND with XRT and mastectomy. ALND with XRT was superior to ALND alone regarding locoregional recurrence (12.7 vs. 34.3 %, p < 0.01) and there was a trend toward improved mortality rates (9.5 vs. 31.4 %, p = 0.09). CONCLUSIONS: There was no difference in survival outcomes between mastectomy and ALND with XRT of patients with OBC. Radiotherapy improves locoregional recurrence and, possibly mortality rates of patients undergoing ALND. Based on this meta-analysis, combined ALND and radiation therapy may appear as the optimal surgical approach in these patients. PMID- 26832882 TI - Pancreatic Ductal Adenocarcinoma is Spread to the Peripancreatic Soft Tissue in the Majority of Resected Cases, Rendering the AJCC T-Stage Protocol (7th Edition) Inapplicable and Insignificant: A Size-Based Staging System (pT1: <=2, pT2: >2 <=4, pT3: >4 cm) is More Valid and Clinically Relevant. AB - BACKGROUND: Most studies have failed to identify any prognostic value of the current T-stage protocol for pancreatic ductal adenocarcinoma (PDAC) by the American Joint Committee on Cancer and the Union for International Cancer Control unless some grouping was performed. METHODS: To document the parameters included in this T-stage protocol, 223 consecutive pancreatoduodenectomy specimens with PDAC were processed by a uniform grossing protocol. RESULTS: Peripancreatic soft tissue (PST) involvement, the main pT3 parameter, was found to be inapplicable and irreproducible due to lack of a true capsule in the pancreas and variability in the amount and distribution of adipose tissue. Furthermore, 91 % of the cases showed carcinoma in the adipose tissue, presumably representing the PST, and thus were classified as pT3. An additional 4.5 % were qualified as pT3 due to extension into adjacent sites. The T-stage defined as such was not found to have any correlation with survival (p = 0.4). A revised T-stage protocol was devised that defined pT1 as 2 cm or smaller, pT2 as >2-4 cm, and pT3 as larger than 4 cm. This revised protocol was tested in 757 consecutive PDACs. The median and 3-year survival rates of this size-based protocol were 26, 18, 13 months, and 40 %, 26 %, 20 %, respectively (p < 0.0001). The association between higher T-stage and shorter survival persisted in N0 cases and in multivariate modeling. Analysis of the Surveillance, Epidemiology, and End Results database also confirmed the survival differences (p < 0.0001). CONCLUSIONS: This study showed that resected PDACs are already spread to various surfaces of the pancreas, leaving only about 4 % of PDACs to truly qualify as pT1/T2, and that the current T-stage protocol does not have any prognostic correlation. In contrast, as shown previously in many studies, size is an important prognosticator, and a size-based T-stage protocol is more applicable and has prognostic value in PDAC. PMID- 26832885 TI - The Current Evidence of Integrative Approaches to Pediatric Asthma. AB - Asthma is a complex, multifactorial, and inflammatory chronic condition, and many children who are diagnosed with asthma integrate complementary therapies into their overall care. Due to the chronic nature of asthma, potentially negative side effects of long-term use of allopathic medications, and desire for natural approaches, patients and their families turn toward complementary therapies. Up to 89% of parents use complementary and alternative medicine (CAM) to treat their child's asthma. This article reviews the current evidence on the most commonly used complementary therapies for pediatric asthma. PMID- 26832886 TI - Integrative Nutrition for Pediatrics. AB - Food is essential for life. Yet, poor food choices may cause poor health. Dietary manipulation is frequently integrated into the management of common chronic pediatric conditions. Parents seek dietary information to have more control over child's condition and to avoid side effects of medicine. This article reviews selected diets for a few common pediatric disorders including eczema, attention deficit hyperactivity disorder, headache and migraine, non-celiac gluten sensitivity, and irritable bowel syndrome. PMID- 26832887 TI - Inferring the Dynamics of Effective Population Size Using Autosomal Genomes. AB - Next-generation sequencing technology has provided a great opportunity for inferring human demographic history by investigating changes in the effective population size (Ne). In this report, we introduce a strategy for estimating Ne dynamics, allowing the exploration of large multi-locus SNP datasets. We applied this strategy to the Phase 1 Han Chinese samples from the 1000 Genomes Project. The Han Chinese population has undergone a continuous expansion since 25,000 years ago, at first slowly from about 7,300 to 9,800 (at the end of the last glacial maximum about 15,000 YBP), then more quickly to about 46,000 (at the beginning of the Neolithic about 8,000 YBP), and then even more quickly to reach a population size of about 140,000 (recently). PMID- 26832889 TI - Cold Contact Urticaria Following Vaccination: Four Cases. PMID- 26832888 TI - Effects of progesterone and vitamin D on outcome of patients with acute traumatic spinal cord injury; a randomized, double-blind, placebo controlled study. AB - BACKGROUND: Steroid hormones offer promising therapeutic perspectives during the acute phase of spinal cord injury (SCI) while the role of progesterone and vitamin D remain controversial. The aim of the current study was to investigate the effects of progesterone and vitamin D on functional outcome of patients with acute traumatic SCI. METHODS: This was a randomized clinical trial including 64 adult patients with acute traumatic SCI admitted within 8 hours of injury. All the patients received methylprednisolone on admission according to standard protocol (30 mg/kg as bolus dose and 15 mg/kg each 3 hours up to 24 hours). Patients were randomly assigned to receive intramuscular injection of 0.5 mg/kg progesterone twice daily and 5ug/kg oral vitamin D3 twice daily up to 5 days (n = 32) or placebo (n = 32). Patients were visited 6 days, 3 and 6 months after injury and motor and sensory function was assessed according to American Spinal Injury Association (ASIA) score. RESULTS: There was no significant difference between two study groups regarding age (P = 0.341), sex (P = 0.802) and therapy lag (P = 0.609). The motor powers and sensory function increased significantly after 6 months in both study groups. Those who received progesterone and vitamin D had significantly higher motor powers and sensory function after 6 months of therapy. Those who received the therapy within 4 hours of injury, had significantly higher motor powers and sensory function 6 months after treatment in progesterone and vitamin D group. Therapy lag was negatively associated with 6 month motor powers and sensory function in progesterone and vitamin D group. CONCLUSIONS: Administration of progesterone and vitamin D in acute phase of traumatic SCI is associated with better functional recovery and outcome. PMID- 26832890 TI - [Association between occupational stress and presenteeism among medical staff at grade A tertiary hospitals in Shanghai, China]. AB - OBJECTIVE: To investigate the current status of occupational stress and presenteeism among medical staff at grade A tertiary hospitals in Shanghai, China, and to analyze the association between occupational stress and presenteeism. METHODS: A total of 2356 healthcare workers from eight grade A tertiary hospitals in Shanghai were investigated by stratified random sampling. All the subjects were asked to complete self-administered questionnaires with informed consent. The occupational stress was assessed by the occupational stress core questionnaire. The presenteeism was evaluated by the Stanford Presenteeism Scale. RESULTS: In all subjects, the average score of presenteeism was 15.23 +/- 3.89, and 72.5% felt occupational stress in self-evaluation. There were significant differences in the score of presenteeism between subjects with different ages, education levels, occupations, lengths of service, job titles, and shifts (all P<0.05). There were significant differences in the score of presenteeism and the rate of high presenteeism between subjects with different indices of occupational stress, including job demand, control, social support, and demand-control ratio (P<0.01). High job demand and high demand-control ratio were risk factors for high presenteeism (OR=2.56, 95% CI=2.01~3.27; OR=1.53, 95% CI=1.23~1.90). High social support was a protective factor for high presenteeism (OR=0.23, 95% CI=0.18~0.29). CONCLUSION: The intensity of occupational stress in medical staff from grade A tertiary hospitals is positively correlated with the level of presenteeism. It is important to promote social support to reduce the loss of work efficiency due to presenteeism. PMID- 26832891 TI - [Relationship between occupational stressors and serum levels of thyroid hormones in policemen]. AB - OBJECTIVE: To explore the relationship of occupational stressors with the serum levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH). METHODS: Using convenience sampling and cluster sampling methods, 225 policemen from a local police station in China were enrolled as subjects. Questionnaires were used to investigate demographic features and occupational stressors in those subjects. The serum levels of T3, T4, and TSH were measured by radioimmunoassay. The SPSS 13.0 software was used to perform t test or analysis of variance, partial correlation analysis, and multivariate non-conditional logistic regression analysis. RESULTS: Reward was positively correlated with the level of T3(P<0.05). Daily tension was positively correlated with the level of T4(P<0.05). Psychological demand, effort, and daily tension were negatively correlated with the level of TSH (all P<0.05). The quality of sleep was positively correlated with the level of TSH (P<0.05). The logistic regression analysis revealed that the risk of increase in T3 level in the group with a high score for daily tension was 3.19-fold higher than that in the group with a low score, while the risk of increase in T3 level in the group with a high score for negative emotion was 1.32-fold higher than that in the group with a low score. The risk of increase in TSH level in the group with a high score for negative emotion was 0.43-fold that in the group with a low score. CONCLUSION: The occupational stressors are correlated with the serum levels of thyroid hormones. Occupational stress can result in an increase in T3 level and a decrease in TSH level. However, occupational stress has no effect on T4 level. PMID- 26832892 TI - [Effects of hyperbaric oxygen preconditioning on human stress responses during acute exposure to high altitude]. AB - OBJECTIVE: To explore the effects of hyperbaric oxygen preconditioning (HBOP) on human stress responses during acute exposure to high altitude and the possible mechanism. METHODS: Eight male subjects were treated with HBOP for 3, 5, and 7 days, followed by acute exposure to hypoxia simulating an altitude of 4,000 m. Subjects at rest were divided into sea-level control group, simulated high altitude group, and 5-day HBOP intervention group, while subjects after physical load were divided into sea-level control group, simulated high-altitude group, 3 day HBOP intervention group, and 7-day HBOP intervention group. The physical load test was performed for each subject before and after HBOP, and the plasma levels of dopamine (DA), epinephrine (E), norepinephrine (NE), and adrenocorticotropic hormone (ACTH) were determined before and after exercise. The physical load test was performed by stepping up on to a 30 cm-high stepping stool at a rate of 25/min for 5 minutes, which was a type of moderate physical exercise. The stepping rate and timing were controlled by a metronome. RESULTS: The levels of DA, E, NE, and ACTH at rest and after physical load were significantly higher in subjects acutely exposed to high altitude than in the sea-level control groups (all P<0.05). Moreover, the levels of DA, E, NE, and ACTH at rest were significantly higher after acute exposure to high altitude in the 5-day HBOP intervention group than in the simulated high-altitude group (all P<0.01). Except for the ACTH level in the 3-day HBOP intervention group, the levels of DA, E, NE, and ACTH after physical load were significantly higher after acute exposure to high altitude in the 3-day and 7-day HBOP intervention groups than in the simulated high-altitude group (all P<0.01). CONCLUSION: HBOP can elevate the plasma expression of DA, E, NE, and ACTH, and then speed up the establishment of a new balance of homeostasis to adapt to the acute hypoxia at high altitude. PMID- 26832893 TI - [Relationship between quality of life and disability level in patients with occupational disease]. AB - OBJECTIVE: To investigate the relationship between the quality of life (QOL) and disability level in patients with occupational disease and to investigate the influencing factors for QOL. METHODS: A total of 255 patients with occupational disease were selected from three specialized hospitals dedicated to occupational disease and the department of occupational medicine of one comprehensive hospital using cluster sampling from December 2013 to May 2014. A survey was carried out using WHOQOL-BREF and general questionnaire (including disability level), and statistical analysis was also performed using t test, F test, analysis of variance, and multivariate stepwise regression analysis. RESULTS: The QOL scores of patients with occupational diseases, from high to low, were social domain (11.48 +/- 2.86), psychological domain (10.60 +/- 2.28), physiological domain (10.54 +/- 1.65), and environmental domain (10.50 +/- 2.55), scores of which were significantly lower than the normal levels (P<0.05). QOL showed no significant differences between patients with occupational diseases of different disability levels (P>0.05). Also, QOL showed no significant differences between stage I, II and III patients with pneumoconiosis (P>0.05). The patients with pneumoconiosis were divided into mild, moderate, and severe groups, and the QOL scores of patients with mild pneumoconiosis in psychological and environmental domains were significantly higher than those of the patients with moderate or severe pneumoconiosis (P< 0.05). Patients with occupational poisoning was divided into mild, moderate and severe groups, and the three groups showed no significant differences in QOL score (P>0.05). Multivariate regression analysis showed that the QOL score of each domain was mainly influenced by the degree of lung injury, complications, course of disease, age of onset, income, and employment status. CONCLUSION: The QOL of patients with occupational disease is significantly reduced, and disability level cannot accurately reflect their QOL. The treatment of patients with occupational disease should focus on their complications, and at the same time QOL should also be improved. PMID- 26832894 TI - [Depressive symptoms and influencing factors in employees from thirteen enterprises]. AB - OBJECTIVE: To explore depressive symptoms and influencing factors in employees from 13 enterprises. METHODS: A total of 6711 workers from 13 enterprises were investigated by cluster sampling, and data were collected anonymously between November 2008 and June 2009. Job satisfaction, occupational stressors, strains, coping strategy, and social support were measured using occupational stress instruments, job content questionnaire, and effort-reward imbalance questionnaire. RESULTS: Median and P25~P75 values of depression score were 14 and 9~21, respectively. The depression score of male workers (16.31 +/- 10.12) was significantly higher than that of female workers(14.50 +/- 9.08) (Z=4.09, P<0.01). The depression score of managers was lowest (12.89 +/- 8.70), and the front-line workers scored highest (16.02 +/- 9.94), with a significant difference between the two groups (chi2 =9.90, P<0.01). The depression score of shift workers (16.79 +/- 9.974) was significantly higher than that of non-shift workers (14.81 +/- 9.63) (Z=53.43, P<0.01). The depression scores of workers with weekly job times of <= 40 h, ~50 h, ~59 h, and >= 60 h were (14.70 +/- 9.94), (15.76 +/- 9.84), (15.46 +/- 9.91), and (19.70 +/- 10.67), respectively (chi2 = 31.79, P <0.01). Correlation analysis revealed that depression score was negatively correlated with the scores of job control (r=-0.236, P <0.01), reward (r=-0.443, P<0.01), job satisfaction (r=-0.418, P<0.01), positive affectivity (r=-0.307, P <0.01), superior support (r=-0.287, P<0.01), colleague support (r=-0.235, P<0.01), and coping strategy (r=-0.208, P<0.01), but positively correlated with the scores of external effort (r=0.225, P<0.01), inherent effort (r=0.248, P<0.01), psychological demands (r = 0.246, P <0.01), physical demands (r=0.246, P<0.01), and negative affectivity (r=0.525, P<0.01). Multivariate logistic regression analysis revealed that the risk of depressive symptoms in workers with high negative affectivity was about four times as high as that in workers with low negative affectivity. The risks of depressive symptoms in workers with low reward, having disease in the past six months, and with high inherent effort were 1.62, 1.50, and 1.48 times, respectively, as high as those for their counterparts. CONCLUSION: Occupational stress, individual factors, health status, and shift work affect the depressive symptoms of workers. Reducing negative affectivity and increasing rewards are main measures to relieve depressive symptoms. PMID- 26832895 TI - [Study on sociopsychological factors in patients with occupational hand injury]. AB - OBJECTIVE: To investigate the role of sociopsychological factors in occupational hand injury and to provide a reference for intervention measures. METHODS: The sociopsychological factors in 150 patients with occupational hand injury who were admitted to the Department of Hand Surgery from January to June in 2014 and 150 pair-matched normal controls were surveyed using self-made questionnaire and Life Event Scale (LES). A comparative study was carried out using t test, chi2 test, and conditional logistic regression analysis. RESULTS: The demographic characteristics, such as length of service, education level, and marital status, showed significant differences between the two groups (P<0.05) ; the LES total score and values of positive life events and negative life events also showed significant differences between the study group and control group (P<0.01) ; single-factor and multi-factor conditional logistic regression analyses showed that length of service, marital status, and negative events score were statistically significant variables (P<0.01). CONCLUSION: Sociopsychological factors play an important role in the occurrence of occupational hand injury. PMID- 26832896 TI - [Establishment and validation of an indicator system of risk assessment for mechanical cuts]. AB - OBJECTIVE: To establish an indicator system of risk assessment for mechanical cuts, and to validate the system using examples. METHODS: An indicator system was proposed by the expert investigation method. The index weight, expert authority coefficient, and degree of coordination were determined. The reasonability and stability of the expert questionnaire were evaluated by the reliability analysis. Some on-site examples were given to validate the indicator system. RESULTS: An indicator system containing 3 first-class indicators, 10 second-class indicators, and 34 third-class indicators was obtained by screening indicators using the boundary value method and the assignment transformation method. The average expert authority coefficient was 0.79. The average expert coordination coefficient was 0.47. The overall reliability coefficient was 0.884. The scores obtained using the indicator system were significantly correlated with the actual injury results in six workplaces (r=0.866, P<0.01). CONCLUSION: The indicator system of risk assessment for mechanical cuts proposed in this study is reasonable and highly consistent with the actual injury results. However, this indicator system still needs further validation and optimization. PMID- 26832897 TI - [A study of relationship between occupational stress and diseases in secondary school teachers]. AB - OBJECTIVE: To analyze the relationship between occupational stress and diseases in secondary school teachers in a city of Sichuan Province, and to provide a basis for the evaluation of the long-term effects of occupational stress in teachers. METHODS: With secondary school teachers as the target population, the stratified cluster sampling was adopted to conduct three studies among 780, 119, and 689 secondary school teachers in a city of Sichuan Province in 1999, 2005, and 2009, respectively. The Occupational Stress Inventory-Revised Edition (OSI-R) and working ability index (WAI) were used to investigate occupational stress and diseases in secondary school teachers. The variation of occupational stress in secondary school teachers was compared between different periods and the relationship between the intensity of stress and diseases was evaluated, on the basis of which the variation of the relationship over time was analyzed. RESULTS: There were significant differences in occupational stress in secondary school teachers between different periods (P<0.05). The incidence rates of medium and high physiological stress and psychological stress were significantly higher in 2009 than in 1999 (P<0.05). Compared with the year of 1999, the intensity of occupational stress in 2009 changed with cardiovascular, respiratory, and mental diseases. The incidence of abnormal psychological stress was a risk factor for all chronic, respiratory, and mental diseases (OR: 1.88, 2.25, and 5.91). The time dependence of odds ratio was only found in the risk of respiratory diseases: occupational stress resulted in a significant increase in the risk of respiratory diseases over time (P<0.05). Physiological stress was a risk factor for mental diseases (OR=2.31). CONCLUSION: The intensity of occupational stress in secondary school teachers changes over time. Occupational stress elevates the risks of certain diseases and has a time-dependent effect on the risk of respiratory diseases. Occupational stress in secondary school teachers needs more attention and effective prevention. PMID- 26832898 TI - [An investigation of occupational stress, social support, and happiness of junior civil servants]. AB - OBJECTIVE: To investigate the current status of occupational stress, social support, and happiness in junior civil servants in northern Zhejiang Province, China, and to investigate the relationship between occupational stress, social support and happiness. METHODS: A total of 360 junior civil servants from below county-level administrative organizations in Huzhou, Jiaxing, and Hangzhou were surveyed using the job stress questionnaire and social support rating scale for civil servants. RESULTS: The total average score of occupational stress in junior civil servants was 2.52 +/- 0.48, indicating a moderate level of occupational stress; career prospects topped the rank list of sources of occupational stress with a score of 2.90 +/- 0.60; different generations showed significant differences in the sources and total average scores of occupational stress, with the scores of the 1980s, 1990s, 1970s, 1950s, and 1960s groups decreasing in the same order (P<0.01); the occupational stress of males was significantly greater than that of the females (P<0.01). The levels of social support and happiness among the junior civil servants were relatively low, with scores of 38.43 +/- 8.38 and 76.88 +/- 12.77, respectively; different generations also showed significant differences, with the scores of 1980s, 1990s, 1970s, 1950s, and 1960s groups increasing in the same order (P<0.01); females experienced significantly more social support and happiness than males (P<0.01). Sources of occupational stress like superior leaders, work task, tendency to perfection, and career prospects, objective and subjective support, and utilization of the support were significantly related to the happiness of junior civil servants (r=0.405~0.571, P<0.01; beta=0.090~0.210, P <0.01). CONCLUSION: Occupational stress and social support are significantly related to the happiness of junior civil servants. PMID- 26832899 TI - [An investigation of prevalence of malignant tumors in 1204 nurses]. AB - OBJECTIVE: To investigate the prevalence of malignant tumors in nurses and its influencing factors and to provide a reference for protecting the health of nurses. METHODS: Cluster sampling was used to randomly survey 1204 married nurses working in one tumor hospital and two tertiary general hospital in Beijing, China, from June to August in 2014. Using the homemade health questionnaire and medical examination reports, the prevalence of malignant tumors in nurses was analyzed. RESULTS: The prevalence of malignant tumors in nurses was 18.30/00, and the prevalence of malignant tumors in the tumor hospital was the highest, reaching 40.10/00. The prevalence of malignant tumors varied significantly between nurses in different hospitals (P<0.05) and in different departments (P<0.05). The malignant tumors in nurses mainly included breast cancer, thyroid cancer, and cervical cancer. The mean age of nurses suffering from malignant tumors was 41 years, and the mean length of service was 20 years. The hospital and department where nurses worked, as well as their age and length of service, were significantly associated with malignant tumors (P<0.05). CONCLUSION: The prevalence of breast cancer, thyroid cancer, and cervical cancer is high in nurses surveyed, particularly those working in the tumor hospital. Further in depth analysis of the reasons is needed to take preventive interventions for protecting the health of nurses. PMID- 26832900 TI - [Studies on occupational stress intervention in workplaces abroad: a systematic review]. AB - OBJECTIVE: To evaluate the effects of occupational stress intervention in the workplaces abroad by systematic review and to provide a reference for domestic research. METHODS: The Medline database was searched to collect the literature on occupational stress intervention published from January 1 in 2000 to September 4 in 2014, Using standardized forms, the methods, contents, subjects, study design, result indicator, effectiveness and evidence of the intervention were extracted and analyzed. RESULTS: Thirty studies met the inclusion criteria, with a total sample size of 5699 participants, including 20 randomized trials and 10 non randomized or self-controlled studies from 12 countries, such as Germany, Japan, and Britain. The course of intervention ranged from 4 to 16 weeks. Six types of intervention were identified, i.e., cognitive-behavioral treatment (CBT), relaxation technique, physical activity, organization-focused intervention, combined intervention, and multilevel intervention, among which CBT was used most frequently. The outcome variables mainly included social psychological variable and work-related variable. Occupational stress intervention could significantly improve the occupational stress and depressive symptoms, and also had some effects on the work-related outcomes. The effectiveness of the intervention might vary between the subjects with different occupational stress levels before intervention. The effectiveness of the intervention was better at an organizational level than at an individual level, but the effectiveness at a multiple level was not necessarily better than that at a single level. CONCLUSION: Occupational stress intervention is an effective method to improve the occupational stress at workplace. However, the occupational stress level before intervention, the duration and frequency of intervention, measures and level of intervention, and follow-up period have certain influence on the effectiveness of intervention. Future research should pay attention to methodology, focus on organizational level and network-based intervention, and increase the cost-benefit analysis. PMID- 26832901 TI - [Monitoring of hematogenous occupational exposure in medical staff in infectious disease hospital]. AB - OBJECTIVE: To investigate the status and risk factors for hematogenous occupational exposure in medical staff in an infectious disease hospital, and to provide a scientific basis for targeted preventive and control measures. METHODS: The occupational exposure of 395 medical workers in our hospital was monitored from January 2012 to December 2014, among whom 79 individuals with occupational exposure were subjected to intervention and the risk factors for occupational exposure were analyzed. RESULTS: The high-risk group was mainly the nursing staff (69.6%). The incidence of hematogenous occupational exposure was high in medical personnel with a working age under 3 years, aged under 25 years, and at the infection ward, accounting for 63.3%, 72.1%, and 72.2%, respectively. Hepatitis B virus, hepatitis C virus, Treponema pallidum, and human immunodeficiency virus were the primary exposure sources. Sharp injury was the major way of injury (91.1%), with needle stick injury accounting for the highest proportion (86.1%). Injury occurred on the hand most frequently (91.1%). The high-risk links were improper disposal during or after pulling the needle, re-capturing the needle, and processing waste, accounting for 46.8%, 17.7%, and 12.7%, respectively. Seventy-nine professionals with occupational exposure were not infected. CONCLUSION: The main risk factor for hematogenous occupational exposure in medical staff in the infectious disease hospital is needle stick injury. Strengthening the occupational protection education in medical staff in infectious disease hospital, implementing protective measures, standardizing operating procedures in high-risk links, and enhancing the supervision mechanism can reduce the incidence of occupational exposure and infection after exposure. PMID- 26832902 TI - [673 cases of epidemiological survey of adult occupational hand injuries]. PMID- 26832903 TI - [Role of tumor necrosis factor-alpha in spinal cord injury of rabbits with decompression sickness]. AB - OBJECTIVE: To observe the pathological changes in rabbits with spinal cord injury induced by decompression sickness (DCS), and to investigate the role of tumor necrosis factor-alpha (TNF-alpha) in spinal cord injury induced by DCS. METHODS: Rabbits were randomly divided into normal control group, DCS group, and safe decompression group. The rabbit model of DCS was established. Light microscopy, real-time PCR, and immunohistochemical method were used to observe the pathomorphological changes in the thoracolumbar spinal cord and the mRNA and protein expression of TNF-alpha, respectively. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was used to observe the apoptosis in the spinal cord. RESULTS: In the DCS group, cavities formed in the white matter of spinal cord and gliosis occurred around necrotic areas. Moreover, the mRNA and protein expression of TNF-alpha was significantly higher in the DCS group than in the normal control group and the safe decompression group (P<0.01). The results of TUNEL showed that the number of positive apoptotic cells was significantly larger in the DCS group than in the normal control group and the safe decompression group (P<0.05). CONCLUSION: Apoptosis plays an important role in spinal cord injury induced by DCS. In the early stage of DCS, the massive release of TNF-alpha initiates apoptosis and contributes to the pathological changes in spinal cord injury induced by DCS. PMID- 26832904 TI - [Determination method of methylthio acetic acid in urine with gas chromatograph methods]. PMID- 26832905 TI - [Evaluation of uncertainty for determination of tin and its compounds in air of workplace by flame atomic absorption spectrometry]. AB - OBJECTIVE: To investigate the method for uncertainty evaluation of determination of tin and its compounds in the air of workplace by flame atomic absorption spectrometry. METHODS: The national occupational health standards, GBZ/T160.28 2004 and JJF1059-1999, were used to build a mathematical model of determination of tin and its compounds in the air of workplace and to calculate the components of uncertainty. RESULTS: In determination of tin and its compounds in the air of workplace using flame atomic absorption spectrometry, the uncertainty for the concentration of the standard solution, atomic absorption spectrophotometer, sample digestion, parallel determination, least square fitting of the calibration curve, and sample collection was 0.436%, 0.13%, 1.07%, 1.65%, 3.05%, and 2.89%, respectively. The combined uncertainty was 9.3%.The concentration of tin in the test sample was 0.132 mg/m3, and the expanded uncertainty for the measurement was 0.012 mg/m3 (K=2). CONCLUSION: The dominant uncertainty for determination of tin and its compounds in the air of workplace comes from least squares fitting of the calibration curve and sample collection. Quality control should be improved in the process of calibration curve fitting and sample collection. PMID- 26832907 TI - [Determination method of 2-butyne-1,4-diol of workplace air with gas chromatograph method]. PMID- 26832906 TI - [Simultaneous determination of 54 elements in human whole blood by inductively coupled plasma mass spectrometry]. AB - OBJECTIVE: To establish a method for simultaneous determination of 54 elements in whole blood by inductively coupled plasma mass spectrometry (ICP-MS). METHODS: The whole blood sample was digested with nitric acid and hydrogen peroxide in a water bath at 90 degrees C, and then analyzed by ICP-MS with 0.1% ethanol as an matrix-matching agent. RESULTS: A good linear relationship was achieved when the concentrations of the 54 elements in whole blood were in the standard range (all r >0.999). The recovery rate of the sample plus the standard was between 80% and 106%, and the relative standard deviation was less than 5%. The standard material of whole blood was determined and the results met the certification requirements. CONCLUSION: The method is simple, rapid, sensitive, and accurate. It is applicable for simultaneous determination of multi-elements in a large number of whole blood samples. PMID- 26832908 TI - [Research progress in influence of military occupational stress and intervention]. PMID- 26832909 TI - [Research progress of relationship between occupational stress and hypertension]. PMID- 26832910 TI - [Cytotoxicity of indium compounds: research progress]. PMID- 26832911 TI - Longevity and concentration in survival times: the log-scale-location family of failure time models. AB - Evidence suggests that the increasing life expectancy levels at birth witnessed over the past centuries are associated with a decreasing concentration of the survival times. The purpose of this work is to study the relationships that exist between longevity and concentration measures for some regression models for the evolution of survival. In particular, we study a family of survival models that can be used to capture the observed trends in longevity and concentration over time. The parametric family of log-scale-location models is shown to allow for modeling different trends of expected value and concentration of survival times. An extension towards mixture models is also described in order to take into account scenarios where a fraction of the population experiences short term survival. Some results are also presented for such framework. The use of both the log-scale-location family and the mixture model is illustrated through an application to period life tables from the Human Mortality Database. PMID- 26832912 TI - The use of sensory perception indicators for improving the characterization and modelling of total petroleum hydrocarbon (TPH) grade in soils. AB - This paper proposes a multistep approach for creating a 3D stochastic model of total petroleum hydrocarbon (TPH) grade in potentially polluted soils of a deactivated oil storage site by using chemical analysis results as primary or hard data and classes of sensory perception variables as secondary or soft data. First, the statistical relationship between the sensory perception variables (e.g. colour, odour and oil-water reaction) and TPH grade is analysed, after which the sensory perception variable exhibiting the highest correlation is selected (oil-water reaction in this case study). The probabilities of cells belonging to classes of oil-water reaction are then estimated for the entire soil volume using indicator kriging. Next, local histograms of TPH grade for each grid cell are computed, combining the probabilities of belonging to a specific sensory perception indicator class and conditional to the simulated values of TPH grade. Finally, simulated images of TPH grade are generated by using the P-field simulation algorithm, utilising the local histograms of TPH grade for each grid cell. The set of simulated TPH values allows several calculations to be performed, such as average values, local uncertainties and the probability of the TPH grade of the soil exceeding a specific threshold value. PMID- 26832913 TI - Characterisation of the airborne pollen spectrum in Guadalajara (central Spain) and estimation of the potential allergy risk. AB - Aerobiological research into airborne pollen diversity and seasonal variations in pollen counts has become increasingly important over recent decades due to the growing incidence of asthma, rhinitis and other pollen-related allergic conditions. Airborne pollen in Guadalajara (Castilla-La Mancha, Spain) was studied over a 6-year period (2008-2013) using a Hirst-type volumetric spore trap. The highest pollen concentrations were recorded from February to June, coinciding with the pollen season of the pollen types that most contribute to the local airborne pollen spectrum: Cupressaceae (32.2%), Quercus (15.1%), Platanus (13.2%), Olea (8.3%), Populus (7.8%) and Poaceae (7.2%). These are therefore critical months for allergy sufferers. The pollen calendar was typically Mediterranean and comprised 25 pollen types. Between January and March, Cupressaceae pollen concentrations exceeded allergy risk thresholds on 38 days. Other woody species such as Olea and Platanus have a shorter pollen season, and airborne concentrations exceeded allergy risk thresholds on around 13 days in each case. Poaceae pollen concentrations attained allergy risk levels on 26 days between May and July. Other highly allergenic pollen types included Urticaceae and Chenopodiaceae-Amaranthaceae, though these are less abundant than other pollen types in Guadalajara and did not exceed risk thresholds on more than 3 and 5 days, respectively. PMID- 26832914 TI - Causal modelling applied to the risk assessment of a wastewater discharge. AB - Bayesian networks (BNs), or causal Bayesian networks, have become quite popular in ecological risk assessment and natural resource management because of their utility as a communication and decision-support tool. Since their development in the field of artificial intelligence in the 1980s, however, Bayesian networks have evolved and merged with structural equation modelling (SEM). Unlike BNs, which are constrained to encode causal knowledge in conditional probability tables, SEMs encode this knowledge in structural equations, which is thought to be a more natural language for expressing causal information. This merger has clarified the causal content of SEMs and generalised the method such that it can now be performed using standard statistical techniques. As it was with BNs, the utility of this new generation of SEM in ecological risk assessment will need to be demonstrated with examples to foster an understanding and acceptance of the method. Here, we applied SEM to the risk assessment of a wastewater discharge to a stream, with a particular focus on the process of translating a causal diagram (conceptual model) into a statistical model which might then be used in the decision-making and evaluation stages of the risk assessment. The process of building and testing a spatial causal model is demonstrated using data from a spatial sampling design, and the implications of the resulting model are discussed in terms of the risk assessment. It is argued that a spatiotemporal causal model would have greater external validity than the spatial model, enabling broader generalisations to be made regarding the impact of a discharge, and greater value as a tool for evaluating the effects of potential treatment plant upgrades. Suggestions are made on how the causal model could be augmented to include temporal as well as spatial information, including suggestions for appropriate statistical models and analyses. PMID- 26832916 TI - Existence of competing modality dominances. AB - Approximately 40 years of research on modality dominance has shown that humans are inclined to focus on visual information when presented with compounded visual and auditory stimuli. The current paper reports a series of experiments showing evidence of both auditory and visual dominance effects. Using a behavioral oddball task, we found auditory dominance when examining response times to auditory and visual oddballs-simultaneously presenting pictures and sounds slowed down responses to visual but not auditory oddballs. However, when requiring participants to make separate responses for auditory, visual, and bimodal oddballs, auditory dominance was eliminated with a reversal to visual dominance (Experiment 2). Experiment 3 replicated auditory dominance and showed that increased task demands and asking participants to analyze cross-modal stimuli conjunctively (as opposed to disjunctively) cannot account for the reversal to visual dominance. Mechanisms underlying sensory dominance and factors that may modulate sensory dominance are discussed. PMID- 26832915 TI - Efficacy and safety of empagliflozin as add-on to metformin for type 2 diabetes: a systematic review and meta-analysis. AB - PURPOSE: To assess the efficacy and safety of empagliflozin (EMPA) as add-on to metformin (MET) in patients with type 2 diabetes mellitus (T2DM). METHODS: We searched PubMed, Embase, Medline, OVID, Cochrane Library and Web of Science. Randomized controlled trials of EMPA as add-on to MET for T2DM were included. Two investigators independently selected studies, extracted data and assessed the risk of bias. A meta-analysis was conducted by using RevMan 5.3 software and Stata 12 software. RESULTS: Seven trials including 4256 patients were analysed. Compared with placebo, two different doses of EMPA significantly reduced glycated haemoglobin (HbA1c) [10 mg: weighted mean difference (WMD) -0.57 %; 95 % confidence interval (CI) -0.65 to -0.49 %, P < 0.00001; 25 mg: WMD -0.65 %; 95 % CI -0.72 to -0.57 %, P < 0.00001]. Compared with active comparators (two sitagliptin, one linagliptin and one glimepiride), 10 mg of EMPA provided a similar reduction in HbA1c [WMD -0.10 %; 95 % CI -0.23 to 0.03 %, P = 0.13], while 25 mg of EMPA provided a significantly greater reduction in HbA1c [WMD 0.13 %; 95 % CI -0.20 to -0.06 %, P = 0.0005]. In addition, EMPA as add-on to MET also had a favourable effect on body weight and blood pressure. The risk of hypoglycaemia in the EMPA group was similar to the placebo group or active comparator group. CONCLUSIONS: EMPA as add-on to MET was well tolerated and provided additional benefits beyond glucose lowering, such as weight loss and blood pressure reduction. However, high-quality trials with large samples are still needed in order to confirm their long-term safety. PMID- 26832918 TI - Expression of glycine receptor alpha 3 in the rat trigeminal neurons and central boutons in the brainstem. AB - Increasing evidence shows that the homomeric glycine receptor is expressed in axon terminals and is involved in the presynaptic modulation of transmitter release. However, little is known about the expression of the glycine receptor, implicated in the presynaptic modulation of sensory transmission in the primary somatosensory neurons and their central boutons. To address this, we investigated the expression of glycine receptor subunit alpha 3 (GlyRalpha3) in the neurons in the trigeminal ganglion and axon terminals in the 1st relay nucleus of the brainstem by light- and electron-microscopic immunohistochemistry. Trigeminal primary sensory neurons were GlyRalpha3-immunopositive/gephyrin-immunonegative (indicating homomeric GlyR), whereas GlyRalpha3/gephyrin immunoreactivity (indicating heteromeric GlyR) was observed in dendrites. GlyRalpha3 immunoreactivity was also found in the central boutons of primary afferents but far from the presynaptic site and in dendrites at subsynaptic sites. Boutons expressing GlyRalpha3 contained small round vesicles, formed asymmetric synapses with dendrites and were immunoreactive for glutamate. These findings suggest that trigeminal primary afferent boutons receive presynaptic modulation via homomeric, extrasynaptic GlyRalpha3, and that different subtypes of GlyR may be involved in pre- and postsynaptic inhibition. PMID- 26832917 TI - Curdlan blocks the immune suppression by myeloid-derived suppressor cells and reduces tumor burden. AB - Tumor-elicited immunosuppression is one of the essential mechanisms for tumor evasion of immune surveillance. It is widely thought to be one of the main reasons for the failure of tumor immunotherapy. Myeloid-derived suppressor cells (MDSCs) comprise a heterogeneous population of cells that play an important role in tumor-induced immunosuppression. These cells expand in tumor-bearing individuals and suppress T cell responses via various mechanisms. Curdlan, the linear (1 -> 3)-beta-glucan from Agrobacterium, has been applied in the food industry and other sectors. The anti-tumor property of curdlan has been recognized for a long time although the underlying mechanism still needs to be explored. In this study, we investigated the effect of curdlan on MDSCs and found that curdlan could promote MDSCs to differentiate into a more mature state and then significantly reduce the suppressive function of MDSCs, decrease the MDSCs in vivo and down-regulate the suppression in tumor-bearing mice, thus leading to enhanced anti-tumor immune responses. We, therefore, increase the understanding of further mechanisms by which curdlan achieves anti-tumor effects. PMID- 26832919 TI - Arborization patterns of amygdalopetal axons from the rat ventral pallidum. AB - We previously analyzed the arborization patterns of rat ventral pallidal (VP) axons that coursed caudally to innervate the thalamus and brainstem (Tripathi et al. in Brain Struct Funct 218:1133-1157, 2013). Here, we have reconstructed 16 previously undetected axons from the same tracer deposits that follow a more lateral trajectory. Virtually all 16 axons emanating from the different VP compartments collateralized in the extended amygdala system (EAS) and amygdaloid complex. The most frequent targets of axons from the lateral and medial (VPm) VP compartments were the rostral sublenticular extended amygdala, the extended amygdala (EA), the central nucleus of the amygdala and the posterior part of the basolateral amygdaloid nucleus. In contrast, axons from the rostral extension of the VP preferentially innervated the anterior amygdaloid area, the magnocellular preoptic nucleus, and the anterior part of the basomedial amygdaloid nucleus. We additionally found and reconstructed a single corticopetal axon arising from the VPm. The new results show that both direct and indirect projections from the basolateral complex and EAS to the ventral striatopallidal system are reciprocated by VP projections, and suggest that the systems can be activated simultaneously. The results additionally suggest that the amygdaloid complex and cortex are innervated separately from the VP. Finally, the combination of new and previous data indicate that approximately 84 % of VP axons (88/105) participate in basal ganglia circuits, 15 % (16/105) target the amygdaloid complex, and less than 1 % innervate the cortex. PMID- 26832920 TI - mGluR4-containing corticostriatal terminals: synaptic interactions with direct and indirect pathway neurons in mice. AB - Glutamatergic afferents from the cerebral cortex are the main excitatory drive of striatal projection neurons. The metabotropic glutamate receptor 4 (mGluR4) presynaptically modulates transmission at corticostriatal synapses, and is considered as a potent drug target for Parkinson's disease and other brain disorders. To better characterize the anatomical substrate that underlies the functional effects of mGluR4 in the striatum, we undertook electron microscopic localization studies of mGluR4 expression in the mouse striatum. Our data demonstrate that more than 80 % mGluR4-immunoreactive structures are accounted for by unmyelinated axons and axon terminals, and that almost 50 % putative glutamatergic terminals (i.e. forming asymmetric synapses) express mGluR4 in the mouse striatum. Using vGluT1 as a presynaptic marker of glutamatergic corticostriatal boutons, our findings indicate: (1) all striatal mGluR4-positive terminals co-express vGluT1 immunoreactivity, (2) 44.3 % total striatal glutamatergic terminals co-express vGluT1 and mGluR4, and (3) mGluR4 is expressed in 73.4 % of total striatal vGluT1-positive terminals. To determine if mGluR4 terminals target preferentially direct vs. indirect pathway neurons, mGluR4 immunostaining was combined with D1 receptor immunoreactivity. These data showed that around 30 % mGluR4-immunoreactive glutamatergic terminals target D1 receptor positive spines (i.e. direct pathway neurons), while almost 70 % formed synapses with D1 receptor-negative spines (i.e. putative indirect pathway neurons). Thus, these immuno-electron microscopic studies suggest that pre-synaptic mGluR4 in striatal glutamatergic terminals is expressed almost exclusively in cortical boutons to subserve regulatory influences upon a large contingent of corticostriatal terminals that preferentially target putative "indirect" pathway striatal projection neurons in mice. These observations provide a rationale for the use of mGluR4 allosteric potentiator as a potential therapy in Parkinson's disease. PMID- 26832921 TI - Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis. AB - Deep brain stimulation (DBS) is an established symptomatic treatment modality for movement disorders and constitutes an emerging therapeutic approach for the treatment of memory impairment. In line with this, fornix DBS has shown to ameliorate cognitive decline associated with dementia. Nonetheless, mechanisms mediating clinical effects in demented patients or patients with other neurological disorders are largely unknown. There is evidence that DBS is able to modulate neurophysiological activity in targeted brain regions. We therefore hypothesized that DBS might be able to influence cognitive function via activity dependent regulation of hippocampal neurogenesis. Using stimulation parameters, which were validated to restore memory loss in a previous behavioral study, we here assessed long-term effects of fornix DBS. To do so, we injected the thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), after DBS and perfused the animals 6.5 weeks later. A week prior to perfusion, memory performance was assessed in the water maze. We found that acute stimulation of the fornix improved spatial memory performance in the water maze when the probe trial was performed 1 h after the last training session. However, no evidence for stimulation-induced neurogenesis was found in fornix DBS rats when compared to sham. Our results suggest that fornix DBS improves memory functions independent of hippocampal neurogenesis, possibly through other mechanisms such as synaptic plasticity and acute neurotransmitter release. PMID- 26832923 TI - Socioeconomic status is associated with reduced lung function in China: an analysis from a large cross-sectional study in Shanghai. AB - BACKGROUND: An inverse association between socioeconomic status and pulmonary function has emerged in many studies. However, the mediating factors in this relationship are poorly understood, and might be expected to differ between countries. We sought to investigate the relationship between socioeconomic status and lung function in China, a rapidly industrializing nation with unique environmental challenges, and to identify potentially-modifiable environmental mediators. METHODS: We used data from the Shanghai Putuo Study, a cross-sectional study performed in Shanghai, China. Participants completed a questionnaire and spirometry. The primary exposure was socioeconomic status, determined by education level. The primary outcomes were FEV1 and FVC percent predicted. Multiple linear regressions were used to test this association, and the percent explained by behavioral, environmental, occupational, and dietary variables was determined by adding these variables to a base model. RESULTS: The study population consisted of a total of 22,878 study subjects that were 53.3 % female and had a mean age of 48. In the final multivariate analysis, the effect estimates for FEV1 and FVC percent predicted for low socioeconomic status (compared to high) were statistically significant at a p-value of <0.01. Smoking, biomass exposure, mode of transportation to work, a diet low in fruits or vegetables, and occupational category partially attenuated the relationship between SES and lung function. In a fully-adjusted age-stratified analysis, the socioeconomic disparity in lung function widened with increasing age. CONCLUSIONS: We found cross-sectional evidence of socioeconomic disparities in pulmonary function in Shanghai. These differences increased with age and were partially explained by potentially modifiable exposures. PMID- 26832922 TI - Food intake inhibition in rainbow trout induced by activation of serotonin 5-HT2C receptors is associated with increases in POMC, CART and CRF mRNA abundance in hypothalamus. AB - In rainbow trout, the food intake inhibition induced by serotonin occurs through 5-HT2C and 5-HT1A receptors, though the mechanisms involved are still unknown. Therefore, we assessed if a direct stimulation of 5-HT2C and 5-HT1A serotonin receptors (resulting in decreased food intake in rainbow trout), affects gene expression of neuropeptides involved in the control of food intake, such as pro opiomelanocortin (POMC), cocaine- and amphetamine-regulated transcript (CART), corticotrophin releasing factor (CRF), and agouti-related peptide (AgRP). In a first set of experiments, the injection of the 5-HT2C receptor agonists MK212 (60 MUg kg(-1) icv) and WAY 161503 (1 mg kg(-1) ip), and of the 5-HT1A receptor agonist 8-OH-DPAT (1 mg kg(-1) ip and 30 MUg kg(-1) icv) induced food intake inhibition. In a second set of experiments, we observed that the injection of MK212 or WAY 161503 (1 and 3 mg kg(-1)) significantly increased hypothalamic POMC mRNA abundance. CART mRNA abundance in hypothalamus was enhanced by treatment with MK212 and unaffected by WAY 161503. The administration of the 5-HT1A receptor agonist 8-OH-DPAT did not induce any significant variation in the hypothalamic POMC or CART mRNA levels. CRF mRNA abundance was only affected by MK212 that increased hypothalamic values. Finally, hypothalamic AgRP mRNA abundance was only evaluated with the agonist 5-HT2C MK212 resulting in no significant effects. The results show that the reduction in food intake mediated by 5-HT2C receptors is associated with increases in hypothalamic POMC, CART and CRF mRNA abundance. PMID- 26832924 TI - A case report of Anisakis pegreffii (Nematoda, Anisakidae) identified from archival paraffin sections of a Croatian patient. AB - BACKGROUND: This is the first report of anisakiasis in a Croatian patient, evidenced from an archival paraffin-embedded and hematoxylin-eosin stained tissue section. Anisakiasis has been only suspected in the country based on previously detected anti-Anisakis IgE seroprevalence in the healthy coastal population, as well as an acute case where pathohistological and serological findings suggested the diseases, but the migrating larva has not been retrieved. CASE PRESENTATION: Seventy years-old female, operated in 1998 for pulmonary carcinoma, was admitted to the General hospital Sibenik, Croatia in 2003, because of gastric pain and nausea that lasted for couple of days. She was showing good general condition, full mobility and lucidity, subfebrile status. Abdominal palpation inferred acute pain in paraumbilical and ileocecal region. Exploratory right pararectal laparotomy revealed a hardened, 5 cm-long structure, located intraluminally in the sigmoid colon, not perforating colon serosa. The process has been dissected and sent for patohistological diagnosis. Results showed a 2 mm-long whitish nematode spiralised in muscular layer of colon mucosa surrounded by granulomatous inflammation. CONCLUSION: After genomic DNA isolation of the nematode from the histological section, and amplification at the mitochondrial cytochrome oxidase 2 locus, etiological agent has been identified as Anisakis pegreffii. Used methodology suggests that screening of archival suspicious sections is feasible in order to study epidemiology of this zoonotic disease poorly recognised in Croatia. PMID- 26832925 TI - Applications of the scoliosis width-to-length ratio for guiding selection of the surgical approaches of degenerative lumbar scoliosis. AB - BACKGROUND: There does not exist a comprehensive parameter for guiding selection of short or long segment fusion for degenerative lumbar scoliosis (DLS). The aim of our study was to investigate the applications of the width-to-length ratio in guiding selection of the surgical approaches for DLS. METHODS: A retrospective analysis was performed of 142 patients with DLS who underwent operative treatments from July 2000 to January 2012. The scoliosis width-to-length ratios were measured and used as a grouping criterion of surgical approaches. The Oswestry disability index (ODI) was used to evaluate the clinical outcomes. Radiological parameters such as Cobb's angle of main curve, Cobb's angle of compensatory curve were all measured. RESULTS: For patients with width-to-length ratio less than 0.36, the short segment group had better short-term postoperative outcomes with regard to Cobb's angle of main curve, Cobb's angle of compensatory curve and ODI scores compared to the long segment group. However, for patients with width-to-length ratio greater than 0.36, the postoperative outcomes for the long segment group were better compared to the short segment group. CONCLUSIONS: The scoliosis width-to-length ratio can provide a comprehensive preoperative assessment of the severity of the DLS and guiding selection of a therapeutic treatment regimen. Further studies with a larger number of samples and longer term of follow up are warranted. PMID- 26832926 TI - Side Effects and Efficacy of Neuraxial Opioids in Pregnant Patients at Delivery: A Comprehensive Review. AB - Neuraxial opioids are an integral part of obstetric anaesthesia and have contributed to greatly improved analgesia for labour and caesarean delivery, both intraoperatively and postoperatively. Despite these advantages, neuraxial opioids may be associated with a number of side effects, some of which (such as respiratory depression), although rare, may be associated with significant morbidity and mortality. The risk of respiratory depression appears to be increased with less lipophilic opioids such as morphine but can be reduced with careful patient selection and monitoring. Other side effects such as pruritus and nausea and vomiting appear to be dose-related and so can be limited by choosing the appropriate dose to optimise analgesia whilst limiting the adverse effects. Urinary retention, the potential neurotoxic effects of neuraxial opioids and the postulated effects on the foetus are also considered but currently it is felt there is not enough evidence to make strong recommendations with regard to specific drugs or dosage. This review aims to discuss the mechanism and incidence of these side effects as well as, where possible, their prevention. PMID- 26832928 TI - Centrosome amplification induces high grade features and is prognostic of worse outcomes in breast cancer. AB - BACKGROUND: Centrosome amplification (CA) has been reported in nearly all types of human cancer and is associated with deleterious clinical factors such as higher grade and stage. However, previous reports have not shown how CA affects cellular differentiation and clinical outcomes in breast cancer. METHODS: We analyzed centrosomes by immunofluorescence and compared to ploidy and chromosomal instability (CIN) as assessed by 6-chromosome FISH in a cohort of 362 breast cancers with median clinical follow-up of 8.4 years. Centrosomes were recognized by immunofluorescence using antibodies for pericentriolar material (PCM; pericentrin) and centrioles (polyglutamylated tubulin). CA was experimentally induced in cell culture by overexpression of polo-like kinase 4 (PLK4). RESULTS: CA is associated with reduced all-cause and breast cancer-specific overall survival and recurrence-free survival. CA correlates strongly with high-risk subtypes (e.g. triple negative) and higher stage and grade, and the prognostic nature of CA can be explained largely by these factors. A strong correlation between CA and high tumor ploidy demonstrates that chromosome and centrosome doubling often occur in concert. CA is proposed to be a method of inducing CIN via aberrant mitotic cell divisions; consonant with this, we observed a strong correlation between CA and CIN in breast cancers. However, some CA tumors had low levels of CIN, indicating that protective mechanisms are at play, such as centrosome clustering during mitosis. Intriguingly, some high-risk tumors have more acentriolar centrosomes, suggesting PCM fragmentation as another mechanism of CA. In vitro induction of CA in two non-transformed human cell lines (MCF10A and RPE) demonstrated that CA induces a de-differentiated cellular state and features of high-grade malignancy, supporting the idea that CA intrinsically causes high-grade tumors. CONCLUSIONS: CA is associated with deleterious clinical factors and outcomes in breast cancer. Cell doubling events are the most prevalent causes of CA in cancer, although PCM fragmentation may be a secondary cause. CA promotes high-risk breast cancer in part by inducing high-grade features. These findings highlight the importance of centrosome aberrations in the biology of human breast cancer. PMID- 26832930 TI - Self-regulation of healthy nutrition: automatic and controlled processes. AB - BACKGROUND: Self-regulatory behaviour refers to both controlled and automatic processes. When people are distracted, automatic over controlled processes prevail. This was analysed with regard to nutritional behaviour (food choices, beverage intake) in situations of low or high distraction. METHODS: A self concept Implicit Association Test (IAT) was adapted to assess the implicit associations of self (vs. other) with healthy (vs. unhealthy) food. Explicit preferences for healthy and unhealthy food and the diet's healthiness were measured by self-report. Both implicit and explicit measures were used as predictors of nutritional behaviour. Among 90 undergraduates, the choice of fruit versus snack in a food choice task (low distraction) and the amount of mineral water and soft drinks consumed in a taste comparison task to cover liquid intake (high distraction) were observed. RESULTS: In the low distraction situation, food choice was predicted solely by explicit measures. Fruits were chosen less, when unhealthy foods were explicitly liked. In the high distraction situation, mineral water intake was predicted solely by the IAT. Participants implicitly associating themselves with healthy foods drank more mineral water than those implicitly associating themselves with unhealthy foods. CONCLUSIONS: Nutritional behaviour is influenced by both automatic and controlled processes depending on the available capacity for self-regulation. PMID- 26832927 TI - Shared and divergent pathways for flower abscission are triggered by gibberellic acid and carbon starvation in seedless Vitis vinifera L. AB - BACKGROUND: Abscission is a highly coordinated developmental process by which plants control vegetative and reproductive organs load. Aiming at get new insights on flower abscission regulation, changes in the global transcriptome, metabolome and physiology were analyzed in 'Thompson Seedless' grapevine (Vitis vinifera L.) inflorescences, using gibberellic acid (GAc) spraying and shading as abscission stimuli, applied at bloom. RESULTS: Natural flower drop rates increased from 63.1% in non-treated vines to 83% and 99% in response to GAc and shade treatments, respectively. Both treatments had a broad effect on inflorescences metabolism. Specific impacts from shade included photosynthesis inhibition, associated nutritional stress, carbon/nitrogen imbalance and cell division repression, whereas GAc spraying induced energetic metabolism simultaneously with induction of nucleotide biosynthesis and carbon metabolism, therefore, disclosing alternative mechanisms to regulate abscission. Regarding secondary metabolism, changes in flavonoid metabolism were the most represented metabolic pathways in the samples collected following GAc treatment while phenylpropanoid and stilbenoid related pathways were predominantly affected in the inflorescences by the shade treatment. However, both GAc and shade treated inflorescences revealed also shared pathways, that involved the regulation of putrescine catabolism, the repression of gibberellin biosynthesis, the induction of auxin biosynthesis and the activation of ethylene signaling pathways and antioxidant mechanisms, although often the quantitative changes occurred on specific transcripts and metabolites of the pathways. CONCLUSIONS: Globally, the results suggest that chemical and environmental cues induced contrasting effects on inflorescence metabolism, triggering flower abscission by different mechanisms and pinpointing the participation of novel abscission regulators. Grapevine showed to be considered a valid model to study molecular pathways of flower abscission competence acquisition, noticeably responding to independent stimuli. PMID- 26832929 TI - Syndecan-1 (CD138) deficiency increases Staphylococcus aureus infection but has no effect on pathology in a mouse model of peritoneal dialysis. AB - BACKGROUND: Technique failure in peritoneal dialysis (PD) due to fibrosis and angiogenesis is complicated by peritonitis. Staphylococcus aureus infection is one of the most common causes of peritonitis in PD. The heparan sulfate proteoglycan, syndecan-1 (CD138), was reported to regulate fibrosis, angiogenesis, inflammation and S. aureus infection. The objectives of this study were to examine the effects of syndecan-1 on S. aureus infection and histopathology in a PD model. RESULTS: Syndecan-1(-/-) and wild type mice were dialyzed for 4 weeks and infected intraperitoneally with S. aureus. Tissues were collected after 4 h for histomorphometric analysis. Intravital microscopy was used to observe leukocyte recruitment and to quantify syndecan-1 in the parietal peritoneum microcirculation. The dialyzed syndecan-1(-/-) mice were more susceptible to S. aureus infection than undialyzed syndecan-1(-/-) controls and wild type animals. However, peritoneal fibrosis and neovascularization due to PD did not differ between syndecan-1(-/-) and wild type mice. Intravital microscopy showed that in S. aureus infection, syndecan-1 was removed from the subendothelial layer of peritoneal venules but syndecan-1 deficiency did not affect leukocyte recruitment. CONCLUSIONS: This study indicates that, while syndecan-1 is important for providing a barrier to acute S. aureus infection in PD, it does not affect peritoneal fibrosis and angiogenesis. PMID- 26832931 TI - Opioid substitution therapy: Lowering the treatment thresholds. AB - BACKGROUND: Opioid substitution therapy (OST) has been established as the gold standard in treating opioid use disorders. Nevertheless, there is still a debate regarding the qualitative characteristics that define the optimal OST intervention, namely the treatment threshold. The aim of this review is twofold: first, to provide a summary and definition of "treatment thresholds", and second, to outline these thresholds and describe how they related to low and high threshold treatment characteristics and outcomes. METHOD: We searched the main databases of Medline, PubMed, PsycInfo, EMBASE, CINAHL and the Cochrane Library. Original published research papers, reviews, and meta-analyses, containing the eligible keywords: "opioid substitution", "OST", "low threshold", "high threshold" were searched alone and in combination, up to June, 2015. RESULTS: Treatment thresholds were defined as barriers a patient may face prior to and during treatment. The variables of these barriers were classified into treatment accessibility barriers and treatment design barriers. There are increasing numbers of studies implementing low threshold designs with an increasing body of evidence suggesting better treatment outcomes compared to high threshold designs. CONCLUSION: Clinical characteristics of low threshold treatments that were identified to increase the effectiveness of OST intervention include increasing accessibility so as to avoid waiting lists, using personalized treatment options regarding medication choice and dose titration, flexible treatment duration, a treatment design that focuses on maintenance and harm reduction with emphasis on the retention of low adherence patients. PMID- 26832932 TI - Heavy tobacco dependence in suicide attempters making recurrent and medically serious attempts. AB - AIMS: Tobacco dependence and suicidal behaviors have been repeatedly associated in several studies but their relationship is still unclear. We aim to investigate, specifically, the association between the level of tobacco dependence and the severity of suicidal outcomes among suicide attempters, as well as the relationship of impulsivity with both conditions. METHODS: We examined a cross-sectional sample of 542 adult suicide attempters to compare the characteristics of the attempts depending on the level of tobacco dependence, which was assessed with the Fagerstrom test. RESULTS: Smokers with heavy dependence (Fagerstrom >=7) made more attempts and reached higher medical lethality compared to non-smokers. Smokers with moderate dependence were not associated with features of severity in the suicide attempts. The combination of high impulsivity and heavy tobacco dependence showed an additive effect on the number of suicide attempts. CONCLUSIONS: A high or very high level of tobacco dependence could indicate a specific vulnerability leading to more severe suicide attempts. Impulsive attempters with heavy tobacco dependence were particularly at risk. PMID- 26832933 TI - Relationship between early symptoms of alcohol craving and binge drinking 2.5 years later. AB - BACKGROUND: The first self-reported symptoms of nicotine dependence (e.g., as craving) can appear within days to weeks of the onset of occasional use, and the appearance of symptoms predicts future consumption and dependence. We sought to determine whether craving for alcohol occurs in early stages of adolescent alcohol use, and whether it predicts future binge drinking, a prevalent and problematic behavior. METHODS: Longitudinal (30-month) four-wave study of 3415 students (M=12.5 years at baseline) from 29 German schools. Students reported five symptoms of alcohol craving on a scale developed based on well-validated measures for tobacco. Multilevel mixed-effects logistic regression was used to predict having five or more binge episodes by last follow-up, based on the number of symptoms reported before the first lifetime binge. Multiple imputation was used to address study drop-out. RESULTS: At baseline, 23% reported at least one symptom, increasing to 54% at wave 4. Any report of symptoms at baseline was associated with frequency of alcohol use, being present in 100% of daily, 93% of weekly, 87% of monthly, 48% of infrequent drinkers, and 16% of ever drinkers reporting no current alcohol use. Moreover, symptoms at baseline independently predicted frequent binge drinking 2.5 years later, AOR=2.08 (95% CI 1.39, 3.11; p<0.001) among baseline never-bingers, after adjusting for covariates. CONCLUSIONS: Some early-onset drinkers reported symptoms of alcohol craving and loss of control after minimal exposure to alcohol. If replicated, an early screener could be developed to identify those at risk for frequent binge drinking. PMID- 26832935 TI - Risky alcohol use in Danish physicians: Associated with alexithymia and burnout? AB - BACKGROUND: Alcohol abuse may be elicited by psychological problems and can influence physicians' health and patient safety. To act on it, we need knowledge on the prevalence of the disorder and its associations with psychological factors and physicians' well-being. The aim of this study was to explore whether burnout and alexithymia are associated with risky alcohol consumption in physicians and whether burnout mediates the association between alexithymia and risky alcohol consumption. METHODS: In this cross-sectional study, 4,000 randomly selected physicians received an electronic questionnaire by email containing the Alcohol Use Disorders Identification Test (AUDIT), the Maslach Burnout Inventory Human Services-Survey (MBI-HSS) and the Toronto Alexithymia Scale (TAS-20). A total of 1,841 physicians completed the questionnaire (46%). RESULTS: 18.8% reached the criteria for risky alcohol consumption. The likelihood of having risky alcohol consumption was associated with high levels of alexithymia (OR=1.93, 95%CI=1.37 2.74, P<0.001). Moreover, risky alcohol consumption was associated with burnout (OR=1.86, 95%CI=1.13-3.05, P<0.014) and each individual burnout dimension: emotional exhaustion (OR=1.89, 95%CI=1.33-2.69, P<0.001), depersonalisation (OR=2.23, 95%CI=1.53-3.25, P<0.001) and low levels of personal accomplishment (OR=1.66, 95%CI=1.14-2.41, P=0.008). Mediation analysis suggested that the association between alexithymia and risky alcohol consumption was partially mediated through depersonalisation. CONCLUSIONS: The results emphasize a need for enhancing emotional self-awareness in physicians as psychological traits, work pressure and alcohol dependence might be self-reinforcing aspects for the individual physician. As alcohol dependence and burnout may have consequences for patient safety separately, the aggregated influence of these factors has to be examined. PMID- 26832936 TI - Colloidal Quantum Dots for Cost-effective, Miniaturized, and Simple Spectrometers. PMID- 26832934 TI - Differences in IV alcohol-induced dopamine release in the ventral striatum of social drinkers and nontreatment-seeking alcoholics. AB - BACKGROUND: Striatal dopamine (DA) has been implicated in alcohol use disorders, but it is still unclear whether or not alcohol can induce dopamine release in social drinkers. Furthermore, no data exist on dopamine responses to alcohol in dependent drinkers. We sought to characterize the DA responses to alcohol intoxication in moderately large samples of social drinkers (SD) and nontreatment seeking alcoholics (NTS). METHODS: Twenty-four SD and twenty-one NTS received two [(11)C]raclopride (RAC) PET scans; one at rest, and one during an intravenous alcohol infusion, with a prescribed ascent to a target breath alcohol concentration (BrAC), at which it was then "clamped." The alcohol clamp was started 5min after scan start, with a linear increase in BrAC over 15min to the target of 80mg%, the legal threshold for intoxication. Target BrAC was maintained for 30min. Voxel-wise binding potential (BPND) was estimated with MRTM2. RESULTS: IV EtOH induced significant increases in DA in the right ventral striatum in NTS, but not SD. No decreases in DA were observed in either group. CONCLUSIONS: Alcohol intoxication results in distinct anatomic profiles of DA responses in SD and NTS, suggesting that in NTS, the striatal DA system may process effects of alcohol intoxication differently than in SD. PMID- 26832940 TI - Erratum to "Detection and characterization of enteroviruses and parechoviruses in healthy people living in the South of Cote d'Ivoire" [J. Clin. Virol. 71 (2015) 40-43]. PMID- 26832937 TI - Pharmacological basis for the use of Hypericum oblongifolium as a medicinal plant in the management of pain, inflammation and pyrexia. AB - BACKGROUND: The present therapeutic agents for the treatment of pain, inflammation and pyrexia are not very effective and accompanied by various side effects. Therefore, new effective agents are the most wanted. The present study investigates the anti-nociceptive, anti-inflammatory and antipyretic activities of crude methanol extract of Hypericum oblongifolium. METHODS: In vivo acetic acid induced writhing and hot plate tests were used for antinociceptive effects at 100, 200 and 300 mg/kg i.p. The anti-inflammatory and antipyretic potential of methanol extract were tested in carrageenan induced paw edema in mice and yeast induced hyperthermia respectively. RESULTS: The extract doses of 100, 200 and 300 mg/kg i.p. revealed significant inhibitory effect (P < 0.001) in acetic acid induced writhing test. Pretreatment of extract at doses of 100, 200 and 300 mg/kg i.p. produced significant anti-inflammatory effect (P < 0.001) in the carrageenan induced paw edema. The methanol extract also showed significant antipyretic effect in yeast induced hyperthermia in mice during various assessment times. CONCLUSIONS: The methanol extract of H. oblongifolium showed significant anti nociceptive, anti-inflammatory and antipyretic effects in various animal models and thus validates the traditional uses of the plant in said conditions. PMID- 26832938 TI - Histone deacetylase 1 is required for the development of the zebrafish inner ear. AB - Histone deacetylase 1 (HDAC1) has been reported to be important for multiple aspects of normal embryonic development, but little is known about its function in the development of mechanosensory organs. Here, we first confirmed that HDAC1 is expressed in the developing otic vesicles of zebrafish by whole-mount in situ hybridization. Knockdown of HDAC1 using antisense morpholino oligonucleotides in zebrafish embryos induced smaller otic vesicles, abnormal otoliths, malformed or absent semicircular canals, and fewer sensory hair cells. HDAC1 loss of function also caused attenuated expression of a subset of key genes required for otic vesicle formation during development. Morpholino-mediated knockdown of HDAC1 resulted in decreased expression of members of the Fgf family in the otic vesicles, suggesting that HDAC1 is involved in the development of the inner ear through regulation of Fgf signaling pathways. Taken together, our results indicate that HDAC1 plays an important role in otic vesicle formation. PMID- 26832941 TI - The Breastfeeding Pep Talk. PMID- 26832942 TI - Clinical Practice Guideline: Otitis Media with Effusion (Update). AB - OBJECTIVE: This update of a 2004 guideline codeveloped by the American Academy of Otolaryngology-Head and Neck Surgery Foundation, the American Academy of Pediatrics, and the American Academy of Family Physicians, provides evidence based recommendations to manage otitis media with effusion (OME), defined as the presence of fluid in the middle ear without signs or symptoms of acute ear infection. Changes from the prior guideline include consumer advocates added to the update group, evidence from 4 new clinical practice guidelines, 20 new systematic reviews, and 49 randomized control trials, enhanced emphasis on patient education and shared decision making, a new algorithm to clarify action statement relationships, and new and expanded recommendations for the diagnosis and management of OME. PURPOSE: The purpose of this multidisciplinary guideline is to identify quality improvement opportunities in managing OME and to create explicit and actionable recommendations to implement these opportunities in clinical practice. Specifically, the goals are to improve diagnostic accuracy, identify children who are most susceptible to developmental sequelae from OME, and educate clinicians and patients regarding the favorable natural history of most OME and the clinical benefits for medical therapy (eg, steroids, antihistamines, decongestants). Additional goals relate to OME surveillance, hearing and language evaluation, and management of OME detected by newborn screening. The target patient for the guideline is a child aged 2 months through 12 years with OME, with or without developmental disabilities or underlying conditions that predispose to OME and its sequelae. The guideline is intended for all clinicians who are likely to diagnose and manage children with OME, and it applies to any setting in which OME would be identified, monitored, or managed. This guideline, however, does not apply to patients <2 months or >12 years old. ACTION STATEMENTS: The update group made strong recommendations that clinicians (1) should document the presence of middle ear effusion with pneumatic otoscopy when diagnosing OME in a child; (2) should perform pneumatic otoscopy to assess for OME in a child with otalgia, hearing loss, or both; (3) should obtain tympanometry in children with suspected OME for whom the diagnosis is uncertain after performing (or attempting) pneumatic otoscopy; (4) should manage the child with OME who is not at risk with watchful waiting for 3 months from the date of effusion onset (if known) or 3 months from the date of diagnosis (if onset is unknown); (5) should recommend against using intranasal or systemic steroids for treating OME; (6) should recommend against using systemic antibiotics for treating OME; and (7) should recommend against using antihistamines, decongestants, or both for treating OME.The update group made recommendations that clinicians (1) should document in the medical record counseling of parents of infants with OME who fail a newborn screening regarding the importance of follow-up to ensure that hearing is normal when OME resolves and to exclude an underlying sensorineural hearing loss; (2) should determine if a child with OME is at increased risk for speech, language, or learning problems from middle ear effusion because of baseline sensory, physical, cognitive, or behavioral factors; (3) should evaluate at-risk children for OME at the time of diagnosis of an at risk condition and at 12 to 18 months of age (if diagnosed as being at risk prior to this time); (4) should not routinely screen children for OME who are not at risk and do not have symptoms that may be attributable to OME, such as hearing difficulties, balance (vestibular) problems, poor school performance, behavioral problems, or ear discomfort; (5) should educate children with OME and their families regarding the natural history of OME, need for follow-up, and the possible sequelae; (6) should obtain an age-appropriate hearing test if OME persists for 3 months or longer OR for OME of any duration in an at-risk child; (7) should counsel families of children with bilateral OME and documented hearing loss about the potential impact on speech and language development; (8) should reevaluate, at 3- to 6-month intervals, children with chronic OME until the effusion is no longer present, significant hearing loss is identified, or structural abnormalities of the eardrum or middle ear are suspected; (9) should recommend tympanostomy tubes when surgery is performed for OME in a child <4 years old; adenoidectomy should not be performed unless a distinct indication exists (nasal obstruction, chronic adenoiditis); (10) should recommend tympanostomy tubes, adenoidectomy, or both when surgery is performed for OME in a child >=4 years old; and (11) should document resolution of OME, improved hearing, or improved quality of life when managing a child with OME. PMID- 26832943 TI - Linkage disequilibrium, persistence of phase and effective population size estimates in Hereford and Braford cattle. AB - BACKGROUND: The existence of moderate to high levels of linkage disequilibrium (LD) between genetic markers and quantitative trait loci (QTL) affecting traits of interest is fundamental for the success of genome-wide association (GWAS) and genomic selection (GS) studies. Knowledge about the extent and the pattern of LD in livestock populations is essential to determine the density of single nucleotide polymorphisms (SNP) required for accurate GWAS and GS. Moreover, observed LD is related to historical effective population sizes (Ne), and can provide insights into the genetic diversity history of populations. Estimates of the consistency of linkage phase across breeds (R H,B ) can be used to determine if there is sufficient relationship to use pooled reference populations in multi breed GS programs. The objective of this study was to estimate LD levels, persistence of phase and effective population size in Hereford and Braford cattle populations sampled in Brazil. RESULTS: Mean LD estimates, measured using the squared correlation of alleles at two loci (r (2)), obtained between adjacent SNP across all chromosomes were 0.21 +/- 0.27 for Herefords (391 samples with 41,241 SNP) and 0.16 +/- 0.22 for Brafords (2044 samples and 41,207 SNP). Estimated r(2) was > 0.2 and 0.3, respectively, for 34 and 25% of adjacent markers in Herefords, and 26 and 17% in Brafords. Estimated N e for Brafords and Herefords at the current generation was 220 and 153 individuals, respectively. The two breeds demonstrated moderate to strong persistence of phase at all distances (R H,B = 0.53 to 0.97). The largest phase correlations were found in the 0 to 50 Kb bins (R H,B = 0.92 to 0.97). Estimated LD decreased rapidly with increasing distance between SNP, however, useful linkage for GWAS and GS (r(2) > 0.2) was found spanning to ~50 Kb. CONCLUSIONS: Panels containing about 50,000 and 150,000 SNP markers are necessary to detect minimal levels of LD between adjacent markers that would be useful for GWAS and GS studies to Hereford and Braford breeds, respectively. Markers are expected to be linked to the same QTL alleles in distances < 50 Kb in both populations due to observed high persistence of phase levels. PMID- 26832944 TI - Reply to "Granulomatous Mastitis - More data is needed". PMID- 26832945 TI - Signaling in the Rhizosphere. AB - Signaling studies in the rhizosphere have focused on close interactions between plants and symbiotic microorganisms. However, this focus is likely to expand to other microorganisms because the rhizomicrobiome is important for plant health and is able to influence the structure of the microbial community. We discuss here the shaping of the rhizomicrobiome and define which aspects can be considered signaling. We divide signaling in the rhizosphere into three categories: (i) between microbes, (ii) from plants to microorganisms, and (iii) from microorganisms to plants. Signals act on diverse organisms including the plant. Mycorrhizal and rhizobial interkingdom signaling has revealed its pivotal role in establishing associations, and the recent discovery of signaling with non symbiotic microorganisms indicates the important role of communication in shaping the rhizomicrobiome. PMID- 26832946 TI - Keystone Herbivores and the Evolution of Plant Defenses. AB - Plants need to defend themselves against a diverse and dynamic herbivore community. Such communities may be shaped by keystone herbivores that through their feeding alter the plant phenotype as well as the likelihood of attack by other herbivores. Here, we discuss such herbivores that have a large effect on the interaction network structure with associated fitness consequences for the plant, as dominant agents of selection on plant defense traits. Merging the keystone herbivore concept with plant fitness and trait selection frameworks will provide an approach to identify which herbivores drive selection in complex multispecies interactions in natural and agricultural systems. PMID- 26832947 TI - Root-Root Interactions: Towards A Rhizosphere Framework. AB - Plant scientists have made great progress in understanding molecular mechanisms controlling root responses to nutrients of arabidopsis (Arabidopsis thaliana) plants under controlled conditions. Simultaneously, ecologists and agronomists have demonstrated that root-root interactions involve more than competition for nutrients. Here, we highlight the importance of both root exudates and soil microbes for root-root interactions, ubiquitous in natural and agricultural ecosystems. We argue that it is time to bring together the recent insights from both scientific disciplines to fully understand root functioning in the real world. PMID- 26832948 TI - Metabolomics in the Rhizosphere: Tapping into Belowground Chemical Communication. AB - The rhizosphere is densely populated with a variety of organisms. Interactions between roots and rhizosphere community members are mostly achieved via chemical communication. Root exudates contain an array of primary and secondary plant metabolites that can attract, deter, or kill belowground insect herbivores, nematodes, and microbes, and inhibit competing plants. Metabolomics of root exudates can potentially help us to better understand this chemical dialogue. The main limitations are the proper sampling of the exudate, the sensitivity of the metabolomics platforms, and the multivariate data analysis to identify causal relations. Novel technologies may help to generate a spatially explicit metabolome of the root and its exudates at a scale that is relevant for the rhizosphere community. PMID- 26832949 TI - Do neurocognitive deficits in decision making differentiate conduct disorder subtypes? AB - The present study aimed to test whether neurocognitive deficits involved in decision making underlie subtypes of conduct-disorder (CD) differentiated on the basis of callous-unemotional (CU) traits. Eighty-five participants (M age = 10.94 years) were selected from a sample of 1200 children based on repeated assessment of CD and CU traits. Participants completed a multi-method battery of well validated measures of risky decision making and associated constructs of selective attention and future orientation (Stroop, Stoplight, and Delay Discounting Tasks). Findings indicated that impaired decision making, selective attention, and future orientation contribute to the antisocial presentations displayed by children with CD, irrespective of level of CU traits. Youth high on CU traits without CD showed less risky decision making, as indicated by their performance on the Stoplight laboratory task, than those high on both CD and CU traits, suggesting a potential protective factor against the development of antisocial behavior. PMID- 26832950 TI - Posttraumatic symptoms and cognitions in parents of children and adolescents with PTSD. AB - Parents may develop symptoms of distress and dysfunctional cognitions in response to their child's exposure to traumatic events. Additionally, they may also be affected by their own traumatic experiences. This study investigated the frequency of traumatic experiences and of symptoms of posttraumatic stress and depression in a sample of parents of children and adolescents with posttraumatic stress disorder (PTSD). Furthermore, we explored the association of parental symptoms with their dysfunctional cognitions related to their child's trauma. Parents (N = 113) of children and adolescents with PTSD completed the Posttraumatic Diagnostic Scale (PDS), the Beck depression inventory (BDI-II), the State-Trait Anxiety Inventory, and the Posttraumatic Cognitions Inventory. Correlations between symptom measures and dysfunctional cognitions were calculated. The majority (78.8 %) of the parents reported their own potentially traumatic experiences. Furthermore, 33.6 % evaluated their child's trauma as the worst event, 34.5 % rated their own experiences as their worst event, and 26.5 % indicated that their own worst traumatic event was the same type as their child's trauma. The frequency of clinically elevated parental symptoms on the PDS was 48.6 %, and on the BDI-II 32.7 %. Parental symptoms were independent of the reference person of the parental traumatic index event. However, they did correlate significantly with their dysfunctional cognitions (between r = 0.44 and 0.69, p < 0.01). Many parents report their own traumatic experiences and a significant proportion has its own clinically relevant symptoms of distress. Parental psychological symptoms are moderately associated with their dysfunctional cognitions. The results emphasize the need to consider parental distress when treating pediatric PTSD. PMID- 26832953 TI - Addressing Challenges to Implementation of the Contraceptive Coverage Guarantee of the Affordable Care Act. PMID- 26832954 TI - Prevalence and Features of a Probable Diagnosis in First-Visit Headache Patients Based on the Criteria of the Third Beta Edition of the International Classification of Headache Disorders: A Prospective, Cross-Sectional Multicenter Study. AB - OBJECTIVES: This study aimed to determine the characteristics and significance of a probable diagnostic entity for primary headache disorder (PHD). BACKGROUND: A diagnosis of probable primary headache disorder (PPHD) is given when a patient's headache fulfills all but one criteria of the third beta edition of the international classification of headache disorder (ICHD-3beta). Despite the uncertainty regarding this diagnosis, the inclusion of a probable diagnosis entity in this manual may aid in the accurate classification of headache disorders and allow effective treatment strategies to be started at the patient's initial visit. METHODS: This cross-sectional multicenter registry study assessed first-visit patients with complaints of headaches who presented at the outpatient clinics of 11 neurologists in Korea. The classification of a headache disorder was made according to the criteria of the ICHD-3beta by each investigator based on the initial evaluation of the patient or by a consensus meeting for uncertain cases. The rates of a probable diagnosis among PPHD patients were assessed and the clinical characteristics of these patients were compared with those of patients with a diagnosis of definite primary headache disorder (DPHD). RESULTS: A total of 1429 patients were diagnosed with PHD, and 305 (21.3%) of these patients had PPHD. The proportions of PPHD differed among the subtypes of DPHD as follows: migraines (16.1%), tension-type headaches (TTH; 33%), trigeminal autonomic cephalalgia (TAC; 40.9%), and other PHD (14%, P < .001). Patients with PPHD had less severe headache intensity than patients with DPHD (5.8 +/- 2.2 vs. 6.5 +/- 2.1, respectively, P < .001) as well as a shorter duration of headache from onset (median: 1 vs. 4 months, respectively, P < .001). The most common criteria missing for a definite diagnosis in the PPHD patients were total frequency (52.1%), duration of attack (14.4%), and accompanying symptoms (13.1%). CONCLUSIONS: A probable diagnosis was given to 21.3% of the first-visit PHD patients due to incomplete or atypical presentations of the headaches. The incorporation of a probable diagnosis into the ICHD-3beta may be useful for reducing the diagnoses of unspecified headaches. PMID- 26832955 TI - Caspase-1, but Not Caspase-3, Promotes Diabetic Nephropathy. AB - Glomerular apoptosis may contribute to diabetic nephropathy (dNP), but the pathophysiologic relevance of this process remains obscure. Here, we administered two partially disjunct polycaspase inhibitors in 8-week-old diabetic (db/db) mice: M-920 (inhibiting caspase-1, -3, -4, -5, -6, -7, and -8) and CIX (inhibiting caspase-3, -6, -7, -8, and -10). Notably, despite reduction in glomerular cell death and caspase-3 activity by both inhibitors, only M-920 ameliorated dNP. Nephroprotection by M-920 was associated with reduced renal caspase-1 and inflammasome activity. Accordingly, analysis of gene expression data in the Nephromine database revealed persistently elevated glomerular expression of inflammasome markers (NLRP3, CASP1, PYCARD, IL-18, IL-1beta), but not of apoptosis markers (CASP3, CASP7, PARP1), in patients with and murine models of dNP. In vitro, increased levels of markers of inflammasome activation (Nlrp3, caspase-1 cleavage) preceded those of markers of apoptosis activation (caspase-3 and -7, PARP1 cleavage) in glucose-stressed podocytes. Finally, caspase-3 deficiency did not protect mice from dNP, whereas both homozygous and hemizygous caspase-1 deficiency did. Hence, these results suggest caspase-3 dependent cell death has a negligible effect, whereas caspase-1-dependent inflammasome activation has a crucial function in the establishment of dNP. Furthermore, small molecules targeting caspase-1 or inflammasome activation may be a feasible therapeutic approach in dNP. PMID- 26832956 TI - Synthesis and evaluation of membrane permeabilizing properties of cationic amphiphiles derived from the disaccharide trehalose. AB - Cationic amphiphiles derived from trehalose have been synthesized; trehalose analogues substituted with n-pentyl or n-hexyl ethers exhibited membrane disrupting activities against clinically important Gram positive and Gram negative bacteria and fungi. Our results demonstrate that trehalose is a useful disaccharide scaffold for the development of broad-spectrum antimicrobial and antifungal agents. PMID- 26832957 TI - Enzyme replacement therapy prior to haematopoietic stem cell transplantation in Mucopolysaccharidosis Type I: 10 year combined experience of 2 centres. AB - Haematopoietic stem cell transplantation is the treatment of choice for the severe form of Mucopolysaccharidosis Type I, or Hurler syndrome. In many centres standard practice is to deliver enzyme replacement therapy alongside haematopoietic stem cell transplantation to improve the condition of the patient prior to transplant. We report the combined 10 year experience of this approach in two paediatric metabolic and transplant centres. Of 81 patients who underwent a first transplant procedure for Hurler, 88% (71/81) survived and 81% (66/81) were alive and engrafted at a median follow-up of 46 months (range 3-124 months). The incidence of grade II-IV acute and any chronic graft versus host disease was 17% and 11% respectively. Urinary glycosaminoglycans were significantly reduced after a period of enzyme replacement therapy, and further reductions were seen at 13-24 months and 25+months after transplantation. In several individuals with decreased cardiac contractility, an improvement of their condition during enzyme replacement therapy enabled them to undergo transplantation, with one individual receiving full intensity conditioning. PMID- 26832958 TI - (Partial) Loss of BAF250a (ARID1A) in rectovaginal deep-infiltrating endometriosis, endometriomas and involved pelvic sentinel lymph nodes. AB - STUDY HYPOTHESIS: Loss of protein BAF250a (ARID1A) expression is present in women with rectovaginal deep-infiltrating endometriosis (DIE) and endometriosis affecting the pelvic sentinel lymph nodes (PSLN). STUDY FINDING: Partial loss of protein BAF250a was found in some of our patient samples, comprising all endometriosis entities, including rectovaginal DIE and endometriosis affecting the PSLN. WHAT IS KNOWN ALREADY: Loss of BAF250a (BRG-associated factor 250a)/ARIDIA (AT-rich interactive domain 1A) protein expression was identified among endometriosis-associated ovarian carcinomas and ovarian endometriosis, and this phenomenon was described as a possible early event in the transformation of endometriosis into cancer. DIE affecting the bowel/rectovaginal site is the most aggressive presentation of endometriosis and its 'risk' of malignant transformation has not been studied so far. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: We evaluated the immunohistochemical expression of BAF250a protein in 70 samples from patients enrolled in this study who were surgically treated at a tertiary center, university Hospital. The samples submitted to investigation were from rectovaginal DIE (n= 25/30), endometriosis affecting the PSLN (n= 5/7), ovarian endometriosis (n= 20/20) and endometrium from patients without endometriosis used as controls (n= 20/20). MAIN RESULTS AND THE ROLE OF CHANCE: Partial loss (i.e. in one tissue section some cells stained positive for BAF250a while other cells, usually an adjacent group, were negative) of BAF250a protein was identified in 36% (9/25) of rectovaginal DIE samples, 40% (2/5) of endometriosis lesions involving the PSLN, 30% (6/20) of endometriomas, and also in 25% (5/20) of endometrium from controls. We found no statistical correlation between occurrence of partial loss of BAF250a protein and the use or not of hormone medications (P = 0.106), cycle phase (P = 0.917) and stage of disease (P = 0.717). LIMITATIONS, REASONS FOR CAUTION: We only found partial loss of BAF250a protein expression, and in a small population of women, with relatively high frequency in all benign tissues assessed in the present analysis. Therefore, this finding alone should not be correlated directly with the risk of malignant transformation in these lesions. WIDER IMPLICATIONS OF THE FINDINGS: The occurrence of partial loss of BAF250a protein expression in women with rectovaginal DIE and endometriosis affecting the PSLN is described for the first time. The value of this finding as a predictor of malignant transformation in endometriosis must still be clarified and further studied in association with other molecular events, such as PTEN (phosphatase and tensin homolog) deletion and PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) mutation. We might then be able to identify in the future which patients with endometriosis are at higher risk of cancer. STUDY FUNDING AND COMPETING INTERESTS: This study was supported by an internal Charite grant to the Endometriosis Research Center and the authors declare no conflicts of interest. PMID- 26832959 TI - Stabilization of p21 by mTORC1/4E-BP1 predicts clinical outcome of head and neck cancers. AB - The levels, regulation and prognostic value of p21 in head and neck squamous cell carcinomas (HNSCC) has been puzzling for years. Here, we report a new mechanism of regulation of p21 by the mTORC1/4E-BP1 pathway. We find that non phosphorylated 4E-BP1 interacts with p21 and induces its degradation. Accordingly, hyper-activation of mTORC1 results in phosphorylation of 4E-BP1 and stabilization of p21. In HNSCC, p21 levels strongly correlate with mTORC1 activity but not with p53 status. Finally, clinical data indicate that HNSCC patients with p21 and phospho-S6-double-positive tumours present a better disease specific survival. We conclude that over-activation of the mTORC1/4E-BP1/p21 pathway is a frequent and clinically relevant alteration in HNSCC. PMID- 26832960 TI - Transfemoral transcatheter aortic valve implantation in a patient with multiple endovascular aortic stents--a case report. AB - BACKGROUND: In patients undergoing transfemoral transcatheter aortic valve implantation, previous endovascular interventions bear a risk for the valve frame to get stucked to the aortic stents. CASE PRESENTATION: We report on a 75-year old frail patient with severe aortic stenosis and a rapid increase of an infra renal aneurysm. He had a history of multiple endovascular interventions on the aorta. Due to his frail preoperative status we decided to perform a transfemoral transcatheter aortic valve implantation in combination with a simultaneous surgical abdominal aneurysm repair. To allow an atraumatic passage of the Edwards SAPIEN 3 valve across the endovascular stents we used a special technique. CONCLUSIONS: The transfemoral approach in patients with previous endovascular stenting can be performed successfully by a partial inflation of the distal balloon. PMID- 26832961 TI - Does light influence the relationship between a native stem hemiparasite and a native or introduced host? AB - BACKGROUND AND AIMS: There have been very few studies investigating the influence of light on the effects of hemiparasitic plants on their hosts, despite the fact that hemiparasites are capable of photosynthesis but also access carbon (C) from their host. In this study we manipulated light availability to limit photosynthesis in an established hemiparasite and its hosts, and determined whether this affected the parasite's impact on growth and performance of two different hosts. We expected that limiting light and reducing autotrophic C gain in the parasite (and possibly increasing its heterotrophic C gain) would lead to an increased impact on host growth and/or host photosynthesis in plants grown in low (LL) relative to high light (HL). METHODS: The Australian native host Leptospermum myrsinoides and the introduced host Ulex europaeus were either infected or not infected with the native stem hemiparasite Cassytha pubescens and grown in either HL or LL. Photosynthetic performance, nitrogen status and growth of hosts and parasite were quantified. Host water potentials were also measured. KEY RESULTS: In situ midday electron transport rates (ETRs) of C. pubescens on both hosts were significantly lower in LL compared with HL, enabling us to investigate the impact of the reduced level of parasite autotrophy on growth of hosts. Despite the lower levels of photosynthesis in the parasite, the relative impact of infection on host biomass was the same in both LL and HL. In fact, biomass of L. myrsinoides was unaffected by infection in either HL or LL, while biomass of U. europaeus was negatively affected by infection in both treatments. This suggests that although photosynthesis of the parasite was lower in LL, there was no additional impact on host biomass in LL. In addition, light did not affect the amount of parasite biomass supported per unit host biomass in either host, although this parameter was slightly lower in LL than HL for U. europaeus (P = 0.073). We also found no significant enhancement of host photosynthesis in response to infection in either host, regardless of light treatment. CONCLUSIONS: Despite lower photosynthetic rates in LL, C. pubescens did not increase its dependency on host C to the point where it affected host growth or photosynthesis. The impact of C. pubescens on host growth would be similar in areas of high and low light availability in the field, but the introduced host is more negatively affected by infection. PMID- 26832962 TI - Statins and brain dysfunction in intensive care. PMID- 26832964 TI - Reprint of 'A nonlinear parameterization of multivariate electrohysterographical signals'. AB - Electrohysterography is a technique which measures a bioelectrical activity of a uterus. This paper presents an application of a nonlinear parameterization of multivariate electrohysterographical signals for a uterine activity assessment to improve unsatisfactory a labor prediction accuracy by methods published in literature. A multivariate sample entropy used for differentiated 4-channel electrohysterographical signals, general Spearman's correlation and a combined index being the sum of them, were tested. These nonlinear measures use joint information contained in a multivariate signal. The results confirm that the combined index provides the best assessment of uterine contractions: 87% sensitivity and 50% specificity of labor prediction in the studied data. These results should be verified in a prospective study. PMID- 26832965 TI - Colorimetric Strategy for Highly Sensitive and Selective Simultaneous Detection of Histidine and Cysteine Based on G-Quadruplex-Cu(II) Metalloenzyme. AB - In this present work, we proposed a colorimetric strategy for simultaneous detection of histidine and cysteine based on G-quadruplex-Cu(II) metalloenzyme for the first time. Because of the adding of histidine or cysteine, the formation of G-quadruplex-Cu(II) metalloenzyme will be disturbed, thus the catalytic activity to TMB-H2O2 reaction is inversely proportional to the concentration of histidine or cysteine. With this strategy, the limit of detection in experimental measurement for histidine and cysteine is 10 nM and 5 nM, respectively, which are both lower than previous colorimetric arrays. With the help of NEM, cysteine is alkylated and the reaction between Cu(2+) is inhibited, so the selectivity can also be guaranteed. The cost is quite low since the developed array is label free and enzyme free by using low-cost DNA and Cu(2+). More importantly, the colorimetric detection operation is very simple without any further modification process. PMID- 26832963 TI - Rosuvastatin versus placebo for delirium in intensive care and subsequent cognitive impairment in patients with sepsis-associated acute respiratory distress syndrome: an ancillary study to a randomised controlled trial. AB - BACKGROUND: Delirium is common in mechanically ventilated patients and is associated with cognitive impairment lasting at least 1 year after hospital discharge. Preclinical and observational studies suggest that the use of statins might reduce delirium in intensive care. We assessed whether the pleiotropic effects of statins can reduce delirium in intensive care and decrease subsequent cognitive impairment in a randomised controlled trial. METHODS: We did this ancillary study within the SAILS trial, a randomised controlled trial assessing mortality and ventilator-free days for rosuvastatin versus placebo for patients with sepsis-associated acute respiratory distress syndrome. This study was done at 35 hospitals in the USA. Patients were randomly assigned in permuted blocks of eight and stratified by hospital to receive either rosuvastatin (40 mg loading dose and then 20 mg daily until the earliest of 3 days after discharge from intensive care, study day 28, or death) or placebo. Patients and investigators were masked to treatment assignment. Delirium was assessed with the validated Confusion Assessment Method for intensive care. Cognitive function was assessed with tests for executive function, language, verbal reasoning and concept formation, and working, immediate, and delayed memory. We defined cognitive impairment as having one of these domains at least two SDs below population norms or at least two domains at least 1.5 SDs below norms. The primary endpoint was daily delirium status in intensive care up to 28 days in the intention-to-treat population and secondary endpoints were cognitive function at 6 months and 12 months. This trial is registered with ClinicalTrials.gov (NCT00979121 and NCT00719446). FINDINGS: 272 patients were assessed for delirium daily in intensive care. The mean proportion of days with delirium was 34% (SD 30%) in the rosuvastatin group versus 31% (29%) in the placebo group; hazard ratio 1.14, 95% CI 0.92-1.41, p=0.22. At 6 months, 19 (36%) of 53 patients in the rosuvastatin group versus 29 (38%) of 77 in the placebo group had cognitive impairment, with no significant difference between groups (treatment effect 0.93, 95% CI 0.39 2.22; p=0.87). At 12 months, 20 (30%) of 67 patients versus 23 (28%) of 81 patients had cognitive impairment, with no significant difference between groups (treatment effect 1.1, 95% CI 0.5-2.6; p=0.82). INTERPRETATION: Most patients had delirium, with around a third of survivors having cognitive impairment over 1 year of follow-up. Despite encouraging preclinical and observational studies, this trial shows no benefit of rosuvastatin in reducing delirium in intensive care or cognitive impairment during 12 months of follow-up although the study was not powered for superiority. Thus, there is continued need to evaluate interventions aimed at attenuating intensive care and post-intensive-care cognitive impairments commonly observed in this population. FUNDING: National Heart, Lung and Blood Institute; Johns Hopkins Institute for Clinical and Translational Research; the SAILS trial was also supported by AstraZeneca. PMID- 26832967 TI - Intensive care nurses' practice related to experience and shift worked. AB - OBJECTIVE: To analyse the social representations of nurses about intensive care practices comparing the variables 1) time since graduation and 2) shift worked. METHOD: Qualitative field research using social representation theory. Individual interviews were conducted and lexical analysis was applied. STUDY SETTING: Intensive Care Unit of a federal hospital with 21 clinical nurses. FINDINGS: Day shift nurses are more pragmatic and operationally oriented because they deal directly with the general functioning of the unit. Less experienced nurses face difficulties dealing with intensive care contexts, but have a critical view of their practices, while more experienced nurses apply practical knowledge in their decision-making and actions. CONCLUSION: The relationship of proximity or distance from patients, mediated by technology, is related to the domains of knowledge that are required to manage technology and to the role technology plays in intensive care. PMID- 26832966 TI - Lectin binding of human sperm associates with DEFB126 mutation and serves as a potential biomarker for subfertility. AB - Coating on the sperm surface, glycocalyx, plays a key role in sperm motility, maturation and fertilization. A comprehensive profile of sperm surface glycans will greatly facilitate both basic researches and clinical studies. Because of the capability of recognizing different glycan moieties, lectins are widely used in glycobiology. However, lacking high-throughput technology, limited lectins have been reported for analyzing the glycan of human sperm. In this study, we employed a lectin microarray for profiling the surface glycans of human sperm, on which 54 out of 91 lectins showed positive binding. Based on this technique, we compared lectin binding profiling of sperm with homozygous DEFB126 mutation (del/del) with that of wild type (wt/wt). DEFB126 was reported to contribute to the sialylation on sperm surface and its homozygous mutation was related to male subfertility. Six lectins (Jacalin/AIA, GHA, ACL, MPL, VVL and ABA) were found to develop lower binding affinity to sperm with del/del. Further validation showed that these lectins, especially ABA and MPL, can be potential biomarkers for clinical diagnosis of subfertility due to the mutation of DEFB126. Our research provides insight into the detection of some unexplained male subfertility, and the lectin microarray is generally applicable for infertility/subfertility sperm biomarker discovery. PMID- 26832968 TI - Surgical management and outcomes of non-missile open head injury: Report of 44 cases from a single trauma centre. AB - OBJECTIVE: To retrospectively analyse the surgical management and outcomes of non missile open head injuries (NMOHI). METHODS: Forty-four patients who suffered from NMOHI were included. The Glasgow outcome score (GOS), computed tomography (CT), aetiology and outcomes and complications at discharge and during a 6-month follow-up were analysed. All patients underwent debridement. Intracranial haematoma evacuation, decompressive craniectomy (DC) or replacement were performed. RESULTS: Motor vehicle accident and struck by/against were the most common causes (43.2% each). At admission, 33 patients had Glasgow coma scores (GCS) > 8 and 27 of them had a GCS score of > 13. Mean follow-up was 8.7 +/- 4.3 months. All patients underwent debridement, 20 underwent bone fracture replacement and 27 underwent haematoma evacuation; 11 patients underwent haematoma evacuation and DC and one had bilateral DC. Twenty-seven patients showed good recovery; 11 patients had moderate disability; three patients had severe disability; and three patients died. After 6 months, 32 patients had good recovery and the morbidity of severe disability had decreased to 13.6%. Thirteen patients developed intracranial infection. Post-traumatic epilepsy and hydrocephalus was detected in three patients. Cerebrospinal fluid fistula was found in five patients. Only one patient developed a brain abscess after 6 months. CONCLUSIONS: NMOHI yielded satisfactory recovery and achieved good outcomes. PMID- 26832970 TI - Fundamental Ethical Principles in Sports Medicine. AB - In sports medicine, the practice of ethics presents many unique challenges because of the unusual clinical environment of caring for players within the context of a team whose primary goal is to win. Ethical issues frequently arise because a doctor-patient-team triad often replaces the traditional doctor-patient relationship. Conflict may exist when the team's priority clashes with or even replaces the doctor's obligation to player well-being. Customary ethical norms that govern most forms of clinical practice, such as autonomy and confidentiality, are not easily translated to sports medicine. Ethical principles and examples of how they relate to sports medicine are discussed. PMID- 26832971 TI - Confidentiality in Sports Medicine. AB - This article synthesizes existing literature to provide a summary of the ethical issues concerning patient confidentiality in sport. It outlines the medical principle of confidentiality and identifies cross-cultural ethicolegal variations that shape its implementation. Clinicians' multiple obligations, physical environments, and practice and policy contexts are discussed, and research detailing experiences of maintaining patient confidentiality in sport is reviewed. Policy recommendations for enhancing compliance with this ethical principle are summarized. It is argued that the context of sport exacerbates pressures on clinicians to break patient confidentiality, breaches occur regularly, and interventions are required to enhance ethical compliance in sports medicine. PMID- 26832969 TI - MDM2 E3 ligase-mediated ubiquitination and degradation of HDAC1 in vascular calcification. AB - Vascular calcification (VC) is often associated with cardiovascular and metabolic diseases. However, the molecular mechanisms linking VC to these diseases have yet to be elucidated. Here we report that MDM2-induced ubiquitination of histone deacetylase 1 (HDAC1) mediates VC. Loss of HDAC1 activity via either chemical inhibitor or genetic ablation enhances VC. HDAC1 protein, but not mRNA, is reduced in cell and animal calcification models and in human calcified coronary artery. Under calcification-inducing conditions, proteasomal degradation of HDAC1 precedes VC and it is mediated by MDM2 E3 ubiquitin ligase that initiates HDAC1 K74 ubiquitination. Overexpression of MDM2 enhances VC, whereas loss of MDM2 blunts it. Decoy peptide spanning HDAC1 K74 and RG 7112, an MDM2 inhibitor, prevent VC in vivo and in vitro. These results uncover a previously unappreciated ubiquitination pathway and suggest MDM2-mediated HDAC1 ubiquitination as a new therapeutic target in VC. PMID- 26832972 TI - Conflicts of Interest in Sports Medicine. AB - Conflict of interest is common in the practice of medicine, and likely more so in the practice of sports medicine at the highest levels of competition. Two areas where conflict of interest frequently manifest in sports medicine are confidentiality and clinical decision making. Confidentiality can be challenging by the team physician's dual responsibilities to the player-patient and the team. Clinical decision making, traditionally associated with a patient's long term health interests, can be complicated by short term interests rooted in pursuit of winning. These issues are reviewed, hopefully to increase awareness in clinicians who find themselves in these unique situations. PMID- 26832973 TI - Ethical Considerations for Analgesic Use in Sports Medicine. AB - This article provides an overview of commonly used analgesics in athletes and the ethical implications of their use in athletic settings. Given the highly competitive nature of modern-day sports and the economic impact of athletic performance at elite levels, athletes feel more compelled than ever to play with injury, which has led to the widespread use of a variety of analgesic agents. An ethical dilemma often ensues for team physicians who must balance the medical implications of these drugs with pressure from players, coaches, and management. The most commonly used agents and their ethical and rational use are discussed. PMID- 26832974 TI - Team Physicians, Sports Medicine, and the Law: An Update. AB - The recognition of sports medicine and promulgation of practice guidelines for team physicians will push general medical malpractice standards to evolve into a more specialized standard of care for those who practice in this area. To the extent that practicing medicine in the sports context involves calculations that do not arise in typical medical practice, the sports medicine community can help elucidate those issues and create appropriate guidelines that can serve to inform athlete-patients and educate courts. Doing so will help best set the terms by which those who practice sports medicine are judged. PMID- 26832975 TI - Concussion Ethics and Sports Medicine. AB - Despite considerable scientific dispute the science of concussion, there has been a proliferation of position statements and professional guidelines published on sports concussion management over the last 15 years. A number of ethical and clinical problems associated with concussion management protocols remain concerning, (i) diagnosis and management; (ii) conflicts of interest and coercion; (iii) same day return to play; and (iv) reporting, auditing and confidentiality. These issues are critically discussed in the light of recent Consensus Statements. It is argued that the use of independent match day doctors may ameliorate some of these concerns. PMID- 26832976 TI - Rethinking the Standard of Care in Treating Professional Athletes. AB - There is public discussion and debate about the role of the team physician in professional sports. There is uncertainty over whether a separate legal standard of care should apply when treating professional athletes. This article advocates a single standard of care for all patients. This article also proposes that it would be useful for team physicians to develop a consensus that there should be a health policy for professional athletes. This health policy should aspire that professional athletes can complete their career, while minimizing the risk of cognitive or physical injuries that affect later quality of life. PMID- 26832977 TI - Understanding Eating Disorders in Elite Gymnastics: Ethical and Conceptual Challenges. AB - Eating disorders and disordered eating are more common in high performance sports than the general population, and particularly so in high performance aesthetic sports. This paper presents some of the conceptual difficulties in understanding and diagnosing eating disorders in high performance gymnasts. It presents qualitative and quantitative data from a study designed to ascertain the pattern of eating disorder symptoms, depressive symptoms and levels of self-esteem among national and international level gymnasts from the UK in the gymnastic disciplines of sport acrobatics, tumbling, and rhythmic gymnastics. PMID- 26832978 TI - Ethics of Regulating Competition for Women with Hyperandrogenism. AB - The International Association for Athletics Federations (IAAF) has been granted 2 years to submit further evidence showing a correlation between higher levels of testosterone and a competitive advantage. This article first presents the case of Caster Semenya, which triggered the drafting by IAAF of the regulations on eligibility of female athletes to compete in the female category in 2011. Then the IAAF regulations are critically analyzed from a scientific and ethical point of view. Finally, the Court of Arbitration for Sport decision to suspend the regulations pending further evidence provided by IAAF, and what this means for the future of sports, is discussed. PMID- 26832979 TI - The Ethics of Sports Medicine Research. AB - This article explores the background and foundations of ethics in research. Some important documents and codes are mentioned, such as The Belmont Report and the International Conference of Harmonisation. Some influential historical events involving research ethics are recounted. The article provides a detailed discussion of the Declaration of Helsinki, which is considered the international standard for guidelines in medical research ethics. The most salient features of the Declaration are described and related to orthopaedic surgery and sports medicine. Some of the most controversial aspects of the Declaration are discussed, which helps examine contentious areas of research in sports medicine. PMID- 26832980 TI - Ethics in sports medicine is very much a gray area. Introduction. PMID- 26832981 TI - Ethics and the Sports Medicine Physician. PMID- 26832982 TI - [Pneumomediastinum caused by rupture of pneumatoceles]. PMID- 26832983 TI - The self-assembly of redox active peptides: Synthesis and electrochemical capacitive behavior. AB - The present work reports on the synthesis of a redox-tagged peptide with self assembling capability aiming applications in electrochemically active capacitive surfaces (associated with the presence of the redox centers) generally useful in electroanalytical applications. Peptide containing ferrocene (fc) molecular (redox) group (Ac-Cys-Ile-Ile-Lys(fc)-Ile-Ile-COOH) was thus synthesized by solid phase peptide synthesis (SPPS). To obtain the electrochemically active capacitive interface, the side chain of the cysteine was covalently bound to the gold electrode (sulfur group) and the side chain of Lys was used to attach the ferrocene in the peptide chain. After obtaining the purified redox-tagged peptide, the self-assembly and redox capability was characterized by cyclic voltammetry (CV) and electrochemical impedance-based capacitance spectroscopy techniques. The obtained results confirmed that the redox-tagged peptide was successfully attached by forming an electroactive self-assembled monolayer onto gold electrode. The design of redox active self-assembly ferrocene-tagged peptide is predictably useful in the development of biosensor devices precisely to detect, in a label-free platform, those biomarkers of clinical relevance. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 357-367, 2016. PMID- 26832984 TI - A rapid and high-throughput microplate spectrophotometric method for field measurement of nitrate in seawater and freshwater. AB - The well-known zinc-cadmium reduction method is frequently used for determination of nitrate. However, this method is seldom to be applied on field research of nitrate due to the long time consuming and large sample volume demand. Here, we reported a modified zinc-cadmium reduction method (MZCRM) for measurement of nitrate at natural-abundance level in both seawater and freshwater. The main improvements of MZCRM include using small volume disposable tubes for reaction, a vortex apparatus for shaking to increase reduction rate, and a microplate reader for high-throughput spectrophotometric measurements. Considering salt effect, two salinity sections (5~10 psu and 20~35 psu) were set up for more accurate determination of nitrate in low and high salinity condition respectively. Under optimized experimental conditions, the reduction rates were stabilized on 72% and 63% on the salinity of 5 and 20 psu respectively. The lowest detection limit for nitrate was 0.5 MUM and was linear up to 100 MUM (RSDs was 4.8%). Environmental samples assay demonstrated that MZCRM was well consistent with conventional zinc cadmium reduction method. In total, this modified method improved accuracy and efficiency of operations greatly, and would be realized a rapid and high throughput determination of nitrate in field analysis of nitrate with low cost. PMID- 26832985 TI - Infection with equine infectious anemia virus vaccine strain EIAVDLV121 causes no visible histopathological lesions in target organs in association with restricted viral replication and unique cytokine response. AB - The live equine infectious anemia virus (EIAV) vaccine strain EIAVDLV121 was developed by in vitro attenuation of a virulent strain, EIAVLN40, in the 1970s, and it has been demonstrated to induce protective immunity under laboratory and natural EIAV infection conditions. The detailed biological features of this attenuated virus remain to be further investigated. Experimental inoculation with EIAVDLV121 did not result in clinical symptoms even with immunosuppressive treatment in our previous studies. Here, we further investigated whether the replication of the vaccine strain EIAVDLV121 in experimentally infected horses causes histopathological lesions to develop in the targeted organs. Both the lungs and the spleen have been demonstrated to support EIAV replication. By evaluating the gross macroscopic and histological changes, we found that EIAVDLV121 did not cause detectable histopathological lesions and that it replicated several hundred times more slowly than its parental virulent strain, EIAVLN40, in tissues. Immunochemical assays of these tissues indicated that the primary target cells of EIAVDLV121 were monocytes/macrophages, but that EIAVLN40 also infected alveolar epithelial cells and vascular endothelial cells. In addition, both of these viral strains promoted the up- and down-regulation of the expression of various cytokines and chemokines, implicating the potential involvement of these cellular factors in the pathological outcomes of EIAV infection and host immune responses. Taken together, these results demonstrate that the EIAV vaccine strain does not cause obvious histopathological lesions or clinical symptoms and that it induces a unique cytokine response profile. These features are considered essential for EIAVDLV121 to function as an effective live vaccine. PMID- 26832986 TI - Advantages and disadvantages of 3-dimensional printing in surgery: A systematic review. AB - BACKGROUND: Three-dimensional (3D) printing is becoming increasingly important in medicine and especially in surgery. The aim of the present work was to identify the advantages and disadvantages of 3D printing applied in surgery. METHODS: We conducted a systematic review of articles on 3D printing applications in surgery published between 2005 and 2015 and identified using a PubMed and EMBASE search. Studies dealing with bioprinting, dentistry, and limb prosthesis or those not conducted in a hospital setting were excluded. RESULTS: A total of 158 studies met the inclusion criteria. Three-dimensional printing was used to produce anatomic models (n = 113, 71.5%), surgical guides and templates (n = 40, 25.3%), implants (n = 15, 9.5%) and molds (n = 10, 6.3%), and primarily in maxillofacial (n = 79, 50.0%) and orthopedic (n = 39, 24.7%) operations. The main advantages reported were the possibilities for preoperative planning (n = 77, 48.7%), the accuracy of the process used (n = 53, 33.5%), and the time saved in the operating room (n = 52, 32.9%); 34 studies (21.5%) stressed that the accuracy was not satisfactory. The time needed to prepare the object (n = 31, 19.6%) and the additional costs (n = 30, 19.0%) were also seen as important limitations for routine use of 3D printing. CONCLUSION: The additional cost and the time needed to produce devices by current 3D technology still limit its widespread use in hospitals. The development of guidelines to improve the reporting of experience with 3D printing in surgery is highly desirable. PMID- 26832987 TI - The nonrecurrent laryngeal nerve: A clinical anatomic mapping with regard to intraoperative neuromonitoring. AB - BACKGROUND: We investigated the nonrecurrent inferior laryngeal nerve (nrILN), an important variant in the course of the inferior laryngeal nerve (ILN; 0.5-6.0%). Its importance was demonstrated in a clinical case as well as in cadaver specimens, and the pattern was identified with intraoperative neuromonitoring (IONM). METHODS: The ILN and the presence of an nrILN were investigated in 36 formaldehyde-embalmed specimens. Our anatomic findings showed differences in the anatomic course of the ILN and thus produced possible explanations for different IONM signals that would correlate with differences in the anatomic course of the ILN. Preoperative ultrasonographic evaluation of the brachiocephalic trunk and the recurrent laryngeal nerve were used for the exclusion or identification of an nrILN, respectively. RESULTS: We found 2 nrILNs (ascending, horizontal; 6%) in the anatomic specimens. These 2 specimens each showed an aberrant right subclavian artery (lusorial artery) and were, therefore, associated with the absence of a brachiocephalic trunk. The intraoperative case displayed a descending nrILN. Signals derived from the vagus nerve were positive if derived proximal to and negative if derived distal to the branching of an nrILN. By ultrasonographic identification of a normal brachiocephalic trunk, an nrILN could be excluded. CONCLUSION: Surgeons need a working knowledge about nrILNs to avoid recurrent nerve palsy and should be familiar with all the possible course variations in the ILN when IONM signals are absent with vagal stimulation. Moreover, endocrine surgeons need to be able to interpret correctly negative as well as positive signals. Preoperative ultrasonography should ideally be performed, because the presence of a normal brachiocephalic trunk is a quick method to exclude or identify a nrILN. PMID- 26832988 TI - Long-term outcomes after pediatric splenectomy. AB - BACKGROUND: Splenectomy is performed frequently for various and primarily hematologic indications in children and adolescents. We analyzed the long-term outcome after splenectomy (median, 8.7 years) focusing on sepsis, portal vein thrombosis (PVT), and retained accessory spleen. METHODS: In total, 141 consecutive children after open (n = 89; 63%) or laparoscopic (n = 52; 37%) splenectomy from 1991 to 2010 were followed up through nationwide registries for septic infections, PVT, and causes of death. Sixty-six patients (58% of survivors) answered a structured questionnaire on infections, abdominal symptoms, and general health, and 64 (laparoscopic n = 26, open n = 38) consented to ultrasonography of the portal venous system. RESULTS: Median operation age was 8.8 years (range, 1.0-22). Reoperations were required for bleeding after open procedures (n = 1) and retained accessory spleen after laparoscopic procedures (n = 3). Postsplenectomy sepsis occurred after a median of 1.7 years (range, 0.2 5.9) in 11 patients (8%), of whom 10 had an underlying immunodeficiency. No cases of PVT were observed, although the median portal vein flow was 1,130 mL/min (range, 440-2200) and diameter was 9.9 mm (range, 7-15) at a median follow-up of 9.5 years (range, 2.0-22) after splenectomy. Twenty-seven patients (19%) died after 8.7 years (0.03-23.00). The most common cause of death was the underlying malignancy (n = 15), with sepsis being an additional cause of death in 5 patients. CONCLUSION: Postsplenectomy sepsis was associated almost exclusively with an underlying immunodeficiency with a high mortality rate. No PVT was observed. The overall risk of retained accessory spleen was around 7%, and was slightly greater after laparoscopic operation. PMID- 26832989 TI - Comparison of Particle-Associated Bacteria from a Drinking Water Treatment Plant and Distribution Reservoirs with Different Water Sources. AB - This study assessed the characteristics of and changes in the suspended particles and the associated bacteria in an unchlorinated drinking water distribution system and its reservoirs with different water sources. The results show that particle-associated bacteria (PAB) were present at a level of 0.8-4.5 * 10(3) cells ml(-1) with a biological activity of 0.01-0.04 ng l(-1) ATP. Different PAB communities in the waters produced from different sources were revealed by a 16S rRNA-based pyrosequencing analysis. The quantified biomass underestimation due to the multiple cells attached per particle was >= 85%. The distribution of the biologically stable water increased the number of cells per particle (from 48 to 90) but had minor effects on the PAB community. Significant changes were observed at the mixing reservoir. Our results show the characteristics of and changes in suspended PAB during distribution, and highlight the significance of suspended PAB in the distribution system, because suspended PAB can lead to a considerable underestimation of biomass, and because they exist as biofilm, which has a greater mobility than pipe-wall biofilm and therefore presents a greater risk, given the higher probability that it will reach the customers' taps and be ingested. PMID- 26832990 TI - A physiological role of cyclic electron transport around photosystem I in sustaining photosynthesis under fluctuating light in rice. AB - Plants experience a highly variable light environment over the course of the day. To reveal the molecular mechanisms of their photosynthetic response to fluctuating light, we examined the role of two cyclic electron flows around photosystem I (CEF-PSI)--one depending on PROTON GRADIENT REGULATION 5 (PGR5) and one on NADH dehydrogenase-like complex (NDH)--in photosynthetic regulation under fluctuating light in rice (Oryza sativa L.). The impairment of PGR5-dependent CEF PSI suppressed the photosynthetic response immediately after sudden irradiation, whereas the impairment of NDH-dependent CEF-PSI did not. However, the impairment of either PGR5-dependent or NDH-dependent CEF-PSl reduced the photosynthetic rate under fluctuating light, leading to photoinhibition at PSI and consequently a reduction in plant biomass. The results highlight that (1) PGR5-dependent CEF-PSI is a key regulator of rapid photosynthetic responses to high light intensity under fluctuating light conditions after constant high light; and (2) both PGR5 dependent and NDH-dependent CEF-PSI have physiological roles in sustaining photosynthesis and plant growth in rice under repeated light fluctuations. The highly responsive regulatory system managed by CEF-PSI appears able to optimize photosynthesis and plant growth under naturally fluctuating light conditions. PMID- 26832991 TI - The Effect of Oxytocin on Third-Party Altruistic Decisions in Unfair Situations: An fMRI Study. AB - Humans display an intriguing propensity to help the victim of social norm violations or punish the violators which require theory-of-mind (ToM)/mentalizing abilities. The hypothalamic peptide oxytocin (OXT) has been implicated in modulating various pro-social behaviors/perception including trust, cooperation, and empathy. However, it is still elusive whether OXT also influences neural responses during third-party altruistic decisions, especially in ToM-related brain regions such as the temporo-parietal junction (TPJ). To address this question, we conducted a pharmacological functional magnetic resonance imaging experiment with healthy male participants in a randomized, double-blind, cross over design. After the intranasal administration synthetic OXT (OXT(IN)) or placebo (PLC), participants could transfer money from their own endowment to either punish a norm violator or help the victim. In some trials, participants observed the decisions made by a computer. Behaviorally, participants under OXT(IN) showed a trend to accelerate altruistic decisions. At the neural level, we observed a strong three-way interaction between drug treatment (OXT/PLC), agency (self/computer), and decision (help/punish), such that OXT(IN) selectively enhanced activity in the left TPJ during observations of others being helped by the computer. Collectively, our findings indicate that OXT enhances prosocial relevant perception by increasing ToM-related neural activations. PMID- 26832992 TI - Poly(amidoamine) Dendrimer-Doxorubicin Conjugates: In Vitro Characteristics and Pseudosolution Formulation in Pressurized Metered-Dose Inhalers. AB - Lung cancers are the leading cause of cancer death for both men and women. A series of PEGylated poly(amidoamine) dendrimer-based doxorubicin (DOX) nanocarriers (G3NH2-mPEG-nDOX) were synthesized and their chemistry tailored for the development of novel pseudosolution formulations in propellant-based metered dose inhalers (pMDIs) with enhanced aerosol characteristics. A pH-labile bond was used to conjugate DOX to dendrimer for controlled intracellular release. We employed a two-step PEGylation strategy to cover a range of DOX loading and PEGylation density. We investigated the impact of pH, PEGylation density, and DOX payload on the release of DOX from the conjugate. We also determined the cellular internalization of the conjugate, the intracellular release kinetics of DOX from the conjugate, and their ability to kill human alveolar carcinoma cells (A549). The acid-labile conjugates sustained the release of DOX in acidic medium, and also intracellularly, as determined by nuclear colocalization studies with confocal microscopy. Meanwhile, DOX was retained in the conjugate at extracellular physiological conditions, indicating their potential to achieve spatial and temporal controlled release profiles. We also observed that the kinetics of cellular entry of the conjugates with DOX increased significantly compared to free DOX. Due to controlled release, the G3NH2-mPEG-nDOX conjugates showed time-dependent cell kill, but their cell kill ability was comparable to free DOX, which suggests their potential in vivo as compared to free DOX. The conjugates were formulated in pMDIs as pseudosolution formulations, with the help of a minimum amount of cosolvent (ethanol; <0.4%; v/v). The physical stability and aerosol characteristics of the conjugates were controlled by the PEGylation density of the carriers: the higher the PEG density, the better the dispersibility and the better the deep lung deposition of the conjugates (fine particle fraction up to ca. 80%). PMID- 26832994 TI - Partial mycoheterotrophy is more widespread among orchids than previously assumed. PMID- 26832993 TI - Massively parallel sequencing of phyllodes tumours of the breast reveals actionable mutations, and TERT promoter hotspot mutations and TERT gene amplification as likely drivers of progression. AB - Phyllodes tumours (PTs) are breast fibroepithelial lesions that are graded based on histological criteria as benign, borderline or malignant. PTs may recur locally. Borderline PTs and malignant PTs may metastasize to distant sites. Breast fibroepithelial lesions, including PTs and fibroadenomas, are characterized by recurrent MED12 exon 2 somatic mutations. We sought to define the repertoire of somatic genetic alterations in PTs and whether these may assist in the differential diagnosis of these lesions. We collected 100 fibroadenomas, 40 benign PTs, 14 borderline PTs and 22 malignant PTs; six, six and 13 benign, borderline and malignant PTs, respectively, and their matched normal tissue, were subjected to targeted massively parallel sequencing (MPS) using the MSK-IMPACT sequencing assay. Recurrent MED12 mutations were found in 56% of PTs; in addition, mutations affecting cancer genes (eg TP53, RB1, SETD2 and EGFR) were exclusively detected in borderline and malignant PTs. We found a novel recurrent clonal hotspot mutation in the TERT promoter (-124 C>T) in 52% and TERT gene amplification in 4% of PTs. Laser capture microdissection revealed that these mutations were restricted to the mesenchymal component of PTs. Sequencing analysis of the entire cohort revealed that the frequency of TERT alterations increased from benign (18%) to borderline (57%) and to malignant PTs (68%; p < 0.01), and TERT alterations were associated with increased levels of TERT mRNA (p < 0.001). No TERT alterations were observed in fibroadenomas. An analysis of TERT promoter sequencing and gene amplification distinguished PTs from fibroadenomas with a sensitivity and a positive predictive value of 100% (CI 95.38-100%) and 100% (CI 85.86-100%), respectively, and a sensitivity and a negative predictive value of 39% (CI 28.65-51.36%) and 68% (CI 60.21-75.78%), respectively. Our results suggest that TERT alterations may drive the progression of PTs, and may assist in the differential diagnosis between PTs and fibroadenomas. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID- 26832995 TI - Inflammation, immunology, stress and depression: a role for kynurenine metabolism in physical exercise and skeletal muscle. PMID- 26832996 TI - Approaching ethical, legal and social issues of emerging forensic DNA phenotyping (FDP) technologies comprehensively: Reply to 'Forensic DNA phenotyping: Predicting human appearance from crime scene material for investigative purposes' by Manfred Kayser. PMID- 26832997 TI - Use of B-mode ultrasonography for measuring femoral muscle thickness in dogs. AB - Assessment of muscle mass is important for evaluating muscle function and rehabilitation outcomes. Ultrasound has recently been successfully used to estimate muscle mass in humans by measuring muscle thickness. This study attempted to standardize procedures for measuring femoral muscle thickness ultrasonographically, as well as quantify the reliability and validity of ultrasound evaluations of muscle thickness compared to measurements made by magnetic resonance imaging (MRI) in dogs. We evaluated the quadriceps femoris (QF), biceps femoris (BF), semitendinosus (ST) and semimembranosus (SM) muscles of 10 clinically healthy Beagle dogs. Scans were taken in 5 different sections divided equally between the greater trochanter and proximal patella. MRI was performed, followed by T1-weighted and contrast-enhanced T1-weighted imaging. Muscle cross-sectional area (CSA) was measured with MRI, and muscle thickness was measured with MRI and ultrasonography. The thickness of the QF, BF and ST muscles as measured by ultrasound at slices 1-3 (from the proximal end to the middle of the femur), 2-4 (middle of the femur) and 2 (more proximal than the middle of the femur), respectively, was correlated with muscle thickness and CSA as measured by MRI. These sites showed a flat interface between muscle and transducer and were situated over belly muscle. No correlation between measurement types was seen in SM muscle. We must confirm this assessment method for various breeds, sizes, ages and muscle pathologies in dogs, thereby confirming that muscle thickness as measured ultrasonographically can reflect muscle function. PMID- 26832999 TI - [Malaria and intestinal protozoa]. AB - Malaria is life threatening and requires urgent diagnosis and treatment. Incidence and mortality are being reduced in endemic areas. Clinical features are unspecific so in imported cases it is vital the history of staying in a malarious area. The first line treatments for Plasmodium falciparum are artemisinin combination therapies, chloroquine in most non-falciparum and intravenous artesunate if any severity criteria. Human infections with intestinal protozoa are distributed worldwide with a high global morbid-mortality. They cause diarrhea and sometimes invasive disease, although most are asymptomatic. In our environment populations at higher risk are children, including adopted abroad, immune-suppressed, travelers, immigrants, people in contact with animals or who engage in oral-anal sex. Diagnostic microscopic examination has low sensitivity improving with antigen detection or molecular methods. Antiparasitic resistances are emerging lately. PMID- 26832998 TI - Receipt of pharmacotherapy for opioid use disorder by justice-involved U.S. Veterans Health Administration patients. AB - BACKGROUND: Pharmacotherapy - methadone, buprenorphine, or naltrexone - is an evidence-based treatment for opioid use disorder, but little is known about receipt of these medications among veterans involved in the justice system. The current study examines receipt of pharmacotherapy for opioid use disorder among veterans with a history of justice involvement at U.S. Veterans Health Administration (VHA) facilities compared to veterans with no justice involvement. METHODS: Using national VHA clinical and pharmacy records, we conducted a retrospective cohort study of veterans with an opioid use disorder diagnosis in fiscal year 2012. Using a mixed-effects logistic regression model, we examined receipt of pharmacotherapy in the 1-year period following diagnosis as a function of justice involvement, adjusting for patient and facility characteristics. RESULTS: The 1-year rate of receipt for pharmacotherapy for opioid use disorder was 27% for prison-involved veterans, 34% for jail/court-involved veterans, and 33% for veterans not justice-involved. Compared to veterans not justice-involved, those prison-involved had 0.75 lower adjusted odds (95% confidence interval [CI]: 0.65-0.87) of receiving pharmacotherapy whereas jail/court-involved veterans did not have significantly different adjusted odds. CONCLUSIONS: Targeted efforts to improve receipt of pharmacotherapy for opioid use disorder among veterans exiting prison is needed as they have lower odds of receiving these medications. PMID- 26833000 TI - [A very abnormal PET-CT]. PMID- 26833001 TI - [Research on the digit ratio of fixed partner and the multi-partner men who have sex with men]. AB - OBJECTIVE: To investigate the digit ratio of men who have sex with men (MSM), and the relationship between digit ratio and the partner types of MSM. METHODS: Participants were required from Yunnan Rainbow Sky, a community organization that specialized in HIV testing, intervention and counseling services for MSM between December 2014 and April 2015. Inclusion criteria of MSM as the following: more than 18 years old; men who have had sex with men; HIV test was negative. Exclusion criteria were as this: those who couldn't attend the research due to disability. Eventually, there were 115 MSM participated in the research. According to the nationality, we adopted 1:1 matched case-control study, and we selected 115 men as control group. According to the partner number of MSM, the MSM were divided into two groups. One group was fixed partner and another was multi-partner. We used a questionnaire to collect the demographic characteristics, knowledge about HIV/AIDS, sexual behaviors during nearly 6 months, sexual orientation, the places where looked for sex partners, sex roles, drug use, preventive services etc. Then, the physical measurements were used to measure the length from second to the fifth finger in MSM group and control group. The results were expressed as nD. The chi-square test was used to compare the demographic differences between MSM group and the control group, and the T test was used to compare the digit ratio between two groups. RESULTS: Among 115 MSM, there were 26% (30/115) MSM who had a fixed partner, and there were 74% (85/115) MSM who had multi-partner. The mean values of digit ratio of MSM presented a trend as 2D:3D < 2D:4D < 3D:4D < 2D:5D < 4D:5D < 3D:5D. The right 2D:4D and 2D:5D of MSM were 0.957 7 +/- 0.048 1 and 1.229 8 +/- 0.083 4, and the mean value was significasntly higher than control group (0.941 4 +/- 0.038 0 and 1.204 1 +/- 0.069 5, t values were 2.84, 2.54 and P values were 0.005, 0.012). The right 2D:4D of the fixed partner group and multi-partner group among MSM were 0.962 2 +/- 0.051 0 and 0.956 1 +/- 0.047 3, respectively, and the mean values were significantly higher than control group (t values were 2.98, 2.83; P values were 0.027, 0.015). CONCLUSION: The proportion of multi-partner MSM was higher, so MSM at a high risk of being HIV infected. Right 2D:4D could be used as a biomarker of the MSM in Kunming, but couldn't reflect the features of MSM whether he has a fixed partner or has several partners. PMID- 26833002 TI - [Coverage of HIV related follow-up intervention and antiretroviral treatment and its correlation among HIV-positive men who have sex with men of 3 cities in China]. AB - OBJECTIVE: To understand the coverage of HIV related intervention and antiviral treatment among HIV-positive men who have sex with men (MSM) and to examine factors of initiating antiretroviral treatment. METHODS: A total of 501 HIV positive MSM were recruited by "snowballing" sampling in Chengdu (160), Chongqing (168) and Guangzhou (173) from January to June, 2013. Participants who were older than18 years, had sex with men, HIV-infected, were living in these 3 cities when survey was conducted were eligible for subjects of this survey. The data were collected by computer assisted survey, including social demography, the coverage of HIV related follow-up intervention and ART, related knowledge level, sexual behaviors in the last 6 months, as well as notification to sexual partners and family. We analyzed the influence factors for initiating ART by Multiple Unconditioned Logistic Regression. RESULTS: Among 501 HIV-positive MSM, the ratio of CD4 counting and HIV viral load testing were 90.8% (455) and 19.4% (97), respectively. The percentage of the latest CD4 counting not more than 350 per ul was 33.0% (150/455). The coverage of initiated ART among the participants who met the qualification was 56.0% (84/150). The multivariable Logistic regression analysis showed that the possibility of not on ART among participants who were migrants increased to 5.21(2.33-11.66) times of the local residents and the possibility among participants who were diagnosed STD in the last year increased to 2.70(1.12-6.55) times of those who were not infected STD, the possibility of not on ART among participants who had sex with male occasional or commercial partner in the last 6 months increased to 2.16(1.03-4.50) times of those who hadn't, and the possibility among participants who had anal sex with condom use in the past 6 months increased to 2.68(1.10-6.50) times of those who couldn't insist using condom. CONCLUSION: There were low coverage of series of HIV/AIDS related intervention services among HIV-positive MSM in Chengdu, Chongqi and Guangzhou. Migrants, had sex with male occasional or commercial partner, had anal sex with condom use in the past 6 months, not infected STD in the last year may be the independent risk factors for HIV-positive MSM to not initiating ART. PMID- 26833003 TI - [Analysis of HIV-1 drug resistance among 1 922 individuals experiencing virological failure of first-line antiretroviral therapy in Henan province]. AB - OBJECTIVE: To study the condition of HIV-1 drug resistance mutation among failures of first-line antiretroviral therapy in Henan province. METHOD: The sub platform of China's legal infectious disease monitoring information reporting system-HIV/AIDS integrated prevention and control data information management system was used to collect the information of patients experiencing first-line antiretroviral treatment failure (virus load >= 1 000 copies/ml) more than one year among nine cities of Henan in 2011. A total of 40 cases with no information and 212 cases with incomplete drug resistance results were deleted, and 1 922 cases were included in this study and genotype resistance testing was carried out. Non-conditional logistic regression analysis was used to analyse the influencing factors of drug resistance mutation. RESULTS: A total of 1 922 cases were included in the analysis. 1 039 cases were males, 833 cases were females, the age was (45.7 +/- 12.1) years, 82.73% (1 590) were married, and 87.93% (1 690) were transmitted by blood. 64.20% (1 234) patients acquired drug resistance. Nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) resistance mutations were found in 62.59% (1 203), 49.74% (956) and 0.94% (18) of subjects, respectively. 42.09% (809) of patients harbored NRTI and NNRTI resistance mutations synchronously. >= 1TAM was the most commonly emerged NRTI resistance mutation (41.94% (806)), the prevalences of TAM-1 and TAM-2 were 8.48% (163) and 4.24% (81), respectively. K65R/N and Q151M complex existed in 23 and 4 patients, respectively. K103N/S was the most commonly emerged NNRTI resistance mutation (34.32% (659)). Non-conditional logistic regression analysis showed that, factors associated with high drug resistance were the following: transmitted by mother to child (OR = 9.05, 95% CI: 1.14-72.12), clinical stage was IV (OR = 1.70, 95% CI: 1.09-2.66) and 5-year-treated (OR = 1.59, 95% CI: 1.03-2.47). Factors associated with low drug resistance were the following: 1-year-treated (OR = 0.19, 95% CI: 0.13-0.27). CONCLUSION: Complex patterns of HIV-1 drug resistance mutations were identified among individuals experiencing failure of first-line antiretroviral therapy in Henan province. Factors associated with high drug resistance were lived in Luohe, Shangqiu, Nanyang, Xinyang, transmitted by mother to child, clinical stage was IV, and 5-year-treated. PMID- 26833004 TI - [Practice and correlates of partner notification of HIV infection status among 307 HIV-infected individuals of Shanghai]. AB - OBJECTIVE: To investigate the situation of notification and HIV antibody testing of sexual partners of people who lived with HIV, and to analyze the factors which could influence the rate of sexual partner notification of Shanghai. METHODS: HIV positive people were recruited from Jiading, Jinan and Xuhui District in Shanghai, all of them were diagnosed with HIV from July 1, 1998 to July 30, 2014, and all of them were >= 16 years old, ruled out poor compliance, unwillingness to cooperate, mental disorders, deaf and other factors that could not properly answer questions. Face to face questionnaires were used to collect demographics, HIV related knowledge, testing of HIV, status of sexual partners before they have been diagnosed with HIV, notification of sexual partners. These questionnaires were self-designed. The differences of notification situation and the HIV positive rate among different sexual partners were compared by chi-square tests. The factors which would influence the rate of sexual partner notification were analyzed by logistic regression, and the OR (95% CI) value was calculated. RESULTS: A total of 307 people living with HIV were surveyed, of these 276 (89.9%) were males and 31 (10.1%) were females. The rates of different sexual partner been notified from spouses, homosexual regular partners, heterosexual regular partners, heterosexual no-regular no-commercial partners, homosexual no regular no-commercial partners to commercial sexual partners were 68.2% (105/154), 44.7% (119/266), 21.4% (22/103), 5.8% (3/52), 5.5% (43/787), and 0.4% (1/235) (chi(2) = 5.22, P < 0.001). Among these been notified sexual partners 277 of them have had HIV antibody tested, 90 persons was HIV-positive, the rate was 32.5%. Confirmed time (OR: 0.37, 95% CI: 0.16-0.86), whether inform staff allowed the HIV-positive people mobilize their sexual partners have HIV-antibody test (OR: 9.63, 95% CI: 3.77-24.55), whether someone else was present during notification (OR: 5.57, 95% CI: 1.96-15.78) and relationship stability (OR: 28.55, 95% CI: 7.93-102.75; OR: 14.13, 95% CI: 4.87-41.02) were associated with HIV-positive people disclosing their infected status to their sexual partners. CONCLUSIONS: The rate of notification to these partners was low, but the HIV antibody positive rate was high among the sexual partners in the three research districts of Shanghai. Shorter confirmed time, inform staff didn't allow the HIV positive people mobilize their partners have HIV-antibody test, no other was present during people was told they were HIV-positive, and no fixed sexual relationship, all these could make lower rate of sexual partners to be notified. PMID- 26833005 TI - [Analysis of early detection of HIV infections by provider initiated HIV testing and counselling in regions with high HIV/AIDS epidemic in China]. AB - OBJECTIVE: To understand provider initiated HIV testing and counseling (PITC) in a region with high HIV/AIDS epidemic in China, and analyze its effect to early detection of HIV infections. METHODS: Between January and December, 2013, 37 county level medical institutions were selected as the study sites, among which, 19 were public medical institutions and 18 were private institutions. According to the related regulation, procedures and contents of PITC, the study was implemented among outpatients and inpatients who seek for doctors in these medical institutions and PITC were provided for them. The 'Individual Investigation Form' was used to record the information and high-risky factors, and the respondents were taken venous blood and given HIV screening and confirmation. All available serum samples of newly found HIV/AIDS cases were tested using the BED HIV Incidence Capture Enzyme Immunoassay (BED-CEIA) to differentiate the long-term infections and new infections (early detected infections). Chi-square analysis was used to compare the differences of characteristics of newly infected patients. RESULTS: Between January and December, 2013, a total of 37 medical institutions provided PITC. 55 164 person times were received HIV screening, among which 658 were HIV positive, and 598 were confirmed to be HIV positive. The 598 cases were all provided transferring service. The differences of age, marital status, education levels, transmission routes and testing institutions had statistical significance to early detection (chi(2) equals to 23.54, 10.50, 17.96, 21.22 and 4.80; P equals to < 0.001, 0.005, < 0.001, < 0.001 and 0.029, respectively). And the early detection proportions among patients aged from 20 to 29 and from 50 to 84 were 47.1% (114/242) and 42.1% (24/57), respectively; the proportions among single and married patients were 37.8% (56/148) and 38.9% (143/368), respectively; the proportion among patients with high school education levels were 42.6% (26/61); the proportion among patients transmitted by fixed heterosexual sexual partners was 46.0% (86/187); the proportion among private hospitals was 40.3% (58/144). CONCLUSION: A certain proportion of HIV infections were early detected by PITC in this region. The HIV early detection proportions among specific age group and population with spouse/fixed sexual partners were relatively high. PMID- 26833006 TI - [Survival time and associated factors of 8 310 AIDS patients initially receiving antiretroviral treatment of Liangshan Yi Autonomous Prefecture, Sichuan province of China]. AB - OBJECTIVE: To investigate the survival time and its impact factors among AIDS patients who initially received antiretroviral treatment (ART) of Liangshan Yi Autonomous Prefecture, Sichuan province. METHODS: A retrospective cohort study was conducted to analyze the information of AIDS patients over 18 years old initially received ART in Liangshan Yi Autonomous Prefecture during 2005-2013, which were downloaded from Chinese AIDS Antiretroviral Therapy DATA Fax Information System. Cox proportion hazard regression model was used to identify impact factors related survival time. RESULTS: Among 8 310 ART AIDS patients who initially received ART, their mean age was (34.59 +/- 9.10) years old, 65.50% (5 443 cases) were infected with HIV through injecting drug use, the mean time from testing HIV positive to starting ART were (24.68 +/- 21.69) months. 436 cases died of AIDS related diseases, 28.67% (125 cases) of them died within the first 6 months of treatment. The cumulative survival rate of receiving ART in 1, 2, 3, 4 5 years were 97.11%, 93.41%, 90.61%, 88.81%, 86.02%, respectively. Multivariate Cox regression analysis showed the male patients receiveing ART were at a higher risk death of AIDS related diseases compared to the females (HR = 1.57, 95% CI: 1.13-2.182), the patients infected with HIV through injecting drug use were at a higher risk deathcompared to the infected through heterosexual transmission (HR = 1.64, 95% CI: 1.20-2.24), before the treatment patients with tuberculosis in recent1 year had higher death hazard as compared to those without tuberculosis (HR = 1.53, 95% CI: 1.05-2.21), in the treatment of the first 3 months of AIDS related diseases or symptoms of AIDS patients had higher death hazard as compared to those not suffer these diseases (HR = 1.80, 95% CI: 1.39-2.34). The patients with baseline CD4 (+) T lymphocytes cell counts < 50/ul (HR = 9.79, 95% CI: 6.03 15.89), 50-199/ul (HR = 3.26, 95% CI: 2.32-4.59), 200-349/ul (HR = 1.69, 95% CI: 1.22-2.34), were at a higher risk death than those with CD4 (+) T lymphocytes cell counts >= 350/ul. CONCLUSION: Accumulate survival rate was higher after initial antiretroviral treatment among AIDS patients in Liangshan Yi Autonomous Prefecture, Sichuan province. AIDS patients who are males, have tuberculosis in recent year, infected HIV via route of intravenous drug use, with AIDS-related illness or symptoms in 3 months before ART, lower baseline CD4 (+) T lymphocyte count have higher risk of death. PMID- 26833007 TI - [Analysis of willingness and influencing factors for usage of pre-exposure prophylaxis among men who have sex with men]. AB - OBJECTIVE: To analyze willingness and influencing factors for usage of pre exposure prophylaxis (PrEP) among men who have sex with men (MSM). METHODS: 887 men who were older than 18 years old and used to have sex with men were recruited through internet between November 27 and December 17, 2013. Data were collected through self designed questionnaire, which was designed to collect information including demography features, willingness of usage of PrEP and associated factors. RESULTS: Totally 760 qualified questionnaires were collected. The ages of surveyed MSM were between 18 and 60, 58.2% (442) were single, 78.9% (600) of them have received college education, 60.4% (459) received annual income less than 60 000 yuan, 73.3% (557) only had sex with men and 77.2% (587) self reported being gay. 32.1% (243/758) of the respondent MSM said they would like to use PrEP. 61.0% (305/500) would like or possibly to take PrEP orally each day. 70.9% (354/499) would keep the same condom using frequency as current situation after using PrEP. In the univariate analysis, the willingness of taking PrEP was ('(2) = 27.61, P < 0.001) lower among those annual income less than 60 000 yuan (27.7% (127/458)) than those annual income higher (44.7% (116/260)); the willingness was significantly ('(2) = 10.99, P = 0.001) higher among those understanding PrEP (35.4% (196/554)) than those not understanding (22.8% (44/206)). In multivariate logistic regression analysis, it suggested that annual income under 60 000 yuan (OR = 0.64 (95% CI: 0.45-0.92)) and understanding PrEP (OR = 1.98 (95% CI: 1.36 2.88)) were influencing factors for usage of PrEP among MSM. CONCLUSION: MSM didn't understand the PrEP sufficiently currently, economic consideration and worries about the side effects will affect their willingness of using PrEP. PMID- 26833008 TI - [Analysis of the risky behaviors among HIV positive female sex workers]. AB - OBJECTIVE: To analyze the characteristics of risky behaviors among different age groups of HIV positive female sex workers, and to explore the strengthening of their management. METHODS: From January to June 2014, 22 814 female sex workers were investigated and tested HIV in 117 sentinel surveillance sites in Yunnan Province, and 181 were confirmed to be HIV antibody positive, who accepted questionnaire surveys. According to the age, the participants were divided into the < 35 years old age group and >= 35 years old age group. The demographic characteristics, knowledge about HIV/AIDS and related risk behaviors characteristics of the two groups were obtained via questionnaire surveys among 181 HIV positive female sex workers, and in-depth qualitative interviews were conducted from among 12 HIV positive sex workers. RESULTS: HIV antibody positive rate was 0.8% (181), the age of the 181 subjects were (35.83 +/- 9.17) years old, 76 cases (42.0%) were < 35 years old, and 105 cases (58.0%) were >= 35 years old. The differences of marital status, workplace class, the last work site among two groups were statistically significant (chi(2) = 20.80, 28.32, 7.83; P < 0.001, P < 0.001, P = 0.020, respectively). Among 181 HIV, the proportion of AIDS awareness was 95.6% (173); the proportion of drug use among >= 35 years old age group was 51.4% (54), which was higher than that in < 35 years old age group (34.2%, 26/76) (chi(2) = 5.30, P = 0.021). 96.7% (175) received condom promotion or HIV counseling and testing in the past year. The proportion of continuing to engage in sexual services over 5 years after HIV infection was 48.5% (51/105) and the proportion of receiving antiretroviral treatment was 69.5% (73/105) in >= 35 years old age group, which were higher than those in the < 35 age group (30.2% (23/76), 52.6% (40/76); chi(2) = 12.26, 5.36; P = 0.002, 0.021, respectively). In depth interviews among 12 HIV positive female sex workers found that regular clients, not consistent use of condoms were the main cause of no condom use. Economic and livelihood factors are important reasons for continuing to engage in sexual services among HIV positive sex workers. CONCLUSION: HIV positive sex workers still have high risk behaviors including continuing to engage in commercial sexual service and no condom use after knowing their HIV infection status, and the proportion of using drugs in the >= 35 years old group was higher than that in < 35 years old group. PMID- 26833009 TI - [Discovery and tracking source of the new subgroup of Chinese Francisella tularensis type B]. AB - OBJECTIVE: To perform laboratory diagnosis and tracking source of a suspected tularemia patient in Beijing. METHODS: A suspected tularemia patient was reported in Beijing city on July 19, 2012. Genomic DNA was extracted from the blood sample of the patient, then general PCR and sequencing of amplicons were conducted using 3 specific genes (fopA, tul4 and 16S rRNA) Francisella tularensis (F.tularensis), and 2 genotyping primers (C1C4 and RD1). Two other laboratories repeated the PCR and sequencing of the fopA in parallel. At the same time, real-time PCR fluorescent ration was performed using 4 targets (fopA, ISFtul2, 23kDa, and tul4), and phylogenetic analysis was carried out using 11 canonical single nucleotide polymorphisms (SNPs) and 4 insertions or deletions. RESULTS: All the 3 specific genes were amplified positively, and sequenced fragments were 409, 407 and 1 053 bp, respectively. The patient was infected by F. tularensis comparing with the whole genome published. Next, amplicons of 151 and 924 bp were obtained by the 2 typing primers after sequencing, respectively. The segment lengths suggested that the patient was infected by the subsp. holarctica. All of the two other laboratories obtained positive data for the PCR and sequencing of the fopA. In addition, all the 4 targets tested positive by real-time PCR for F. tularensis. The Ct value of the fopA, ISFtul2, 23kDa and tul4 were 30, 25, 28, and 30, respectively. The phylogenetic analysis indicated that the whole genome of this case was assigned to a known clade from Russia, which was subgroup B3. CONCLUSION: This case was confirmed to be a tularemia patient, and a new subgroup of F. tularensis type B was found in China. PMID- 26833010 TI - [Study on the superantigen gene profiles of group A Streptococcus isolated from children in Beijing, 2014]. AB - OBJECTIVE: To investigate superantigen gene profiles of group A Streptococcus (GAS) isolated in Beijing pediatric patients in 2014, and to explore the the relationship between superantigen gene profiles with emm types, and GAS infections with diseases. METHODS: A total of 259 GAS strains were isolated from pediatric patients clinically who diagnosed with scarlet fever and pharyngitis from 36 hospitals in Beijing from May to July, 2014.The Superantigens genes of strains were performed by Real-time PCR (speA, speB, speC, speF, speG, speH, speI, speJ, speK, speL, speM, smeZ, ssa). PCR amplification of GAS strain M protein N gene segments were carried ort; products after sequencing comparison were analyzed to determine the GAS types of emm. The differences in distributions of superantigen genes and emm types of GAS isolates were compared between subgroups. RESULTS: Among the 259 GAS strains, the detection rates of 13 superantigens were as the following: speA 48.6% (126), speB 99.2% (257), speC 99.2% (257), speF 98.8% (256), speG 98.5% (255), speH 43.6% (113), speI 46.3% (120), speJ 49.0% (127), smeZ 99.2% (257) and ssa 98.5% (255), respectively, however, speK, speL, and speM were not found. Eleven superantigen gene profiles in all were observed (A-K). The percentage of emm1 strains harbored spe A and speJ were 94.2% (113/120), 95.0% (114/120), respectively, which were significantly higher than those of emm12 strains (5.6% (7/124), 5.6% (7/124), respectively; chi(2) = 191.20, 194.80, P < 0.001). The percentage of emm12 strains harbored speH and speI were 83.9% (104/124), 88.7% (110/124), respectively, which were significantly higher than those of emm1 strains (3.3% (4/120), 4.2% (5/120), respectively; chi(2) = 160.30, 174.90, P < 0.001).The superantigen genotypes of GAS strains and emm types, which were isolated from scarlet fever and pharyngitis cases, were not significant different (P > 0.05). CONCLUSION: The GSA strains isolated in Beijing pediatric patients in 2014, the relevance ratio of speB, speC, speF, smeZ, speG, ssa were higher than others, while speK, speL, and speM were no detected in any GAS strains. The superantigen genes appeared to be associated with the emm type. Furthermore, emm type distribution and superantigen genes were not different between scalet fever and pharyngitis. PMID- 26833011 TI - [Epidemiological investigation of predominance tick and the infectious status of severe fever thrombocytopenia syndrome virus in Penglai and Laizhou counties, Shandong province]. AB - OBJECTIVE: To investigate the predominance ticks and the infectious status of severe fever with thrombocytopenia (SFTSV) in Penglai and Laizhou counties, Shandong province. METHODS: Two towns with high incidence rate were selected in Penglai and Laizhou, respectively, then three villages were selected in each towns. Parasitic ticks were collected from the host skin by hand manually and free ticks manually with white cloth from the grassland, monthly, during April to December in 2011. Samples were classified by original, varieties, developmental stages, then extracted RNA, using Realtime RT-PCR to test severe fever thrombocytopenia syndrome virus, S fragments were amplified with nested PCR, then isolated virus. By neighbor joining method in the phylogenetic tree, the minimum infection rate (MIR) was used to represent the infection status of ticks in novel bunyavirus. RESULTS: A total of 3 145 ticks were collected totally from 5 categories, there were 3 048(96.92%) of Haemaphysalis longicornis, 73(2.32%) of Rhinpicephalus sanguineus, 10(0.32%) of microplus Boophilus, 9(0.29%) of Haemaphysalis campanulata, 5(0.16%) of Dermacentor sinicus, respectively. The positive rate of nucleic acid of 2 044 samples was 6.16% (126/2 044), minimum infection rate (MIR) was 4.01%, there were 122(96.83%) of Haemaphysalis longicornis, 3(2.38%) of Rhinpicephalus sanguineus, and 1(0.79%) of microplus Boophilus, MIR was 4.00%, 4.11%, and 10.00%, respectively. There were no nucleic acid positive samples in Haemaphysalis campanulata and Dermacentor sinicus. The 11 S segments were amplified in 126 positive samples, the homology of S fragment was 95.6%-99.9% with 11 strains isolated from the identified SFTS cases in local area, 3 strains isolated from animals, and 11 strains isolated from other areas. There was no significant difference among original, varieties and developmental stages. CONCLUSION: Haemaphysalis longicornis was the predominant species in Penglai and Laizhou counties, it could be propagation medium with Rhipicephalus sanguineus and microplus Boophilus, S sequence in ticks was higher homology with virus isolated from local SFTS cases. PMID- 26833012 TI - [Levels of phthalate internal exposure levels in pregnant women and influencing factors]. AB - OBJECTIVE: To investigate the levels and influencing factors of phthalate internal exposure in pregnant women (gestation age <= 16 weeks). METHODS: During April to June in 2013, 1 020 pregnant women (gestation age <= 16 weeks) who had established the maternal care manual were recruited in maternal and child health hospital of Siming District, Xiamen city. Participators were asked to complete a questionnaire to obtain information on socio-demographic characteristics, lifestyle behaviors, and antenatal examination and to provide a urine sample. Finally, 998 pregnant women who provided a urine sample and completed the questionnaire were enrolled. Adopting systematic sampling method, 100 ones were selected randomly among 998 pregnant women. High performance liquid chromatography-electrospray ionization-tandern mass was used to determine the concentration of five phthalate monoesters in each urine, including mono-n-methyl phthalate (MMP), mono-ethyl phthalate (MEP), mono-butyl phthalate (MBP), mono benzyl phthalate (MBzP), mono-ethylhexyl phthalate (MEHP). Based on the measurements and questionnaire data, multivariate logistic regression was used to analyze the association between the phthalate monoester levels and potential influential factors. RESULTS: The detection rates of MMP, MEP, MBP, MBzP and MEHP in 100 pregnant urine samples were 94%, 93%, 87%, 83%, 99%, respectively. And the urinary median uncorrected concentrations of MMP, MEP, MBP, MBzP and MEHP in 100 urine samples were 20.56, 17.62, 10.15, 2.03, and 5.12 ng/ml, respectively. Specific gravity-corrected concentration were 20.81, 20.36, 12.88, 2.58, 5.00 ng/ml, respectively. The results of multivariate logistic regression analysis indicated that: education degree was negatively associated with urinary concentration of MMP, MEP, MBP, MBzP and MEHP, OR (95% CI) were 0.495 (0.253 0.966), 0.380 (0.191-0.755), 0.379 (0.186-0.774), 0.401 (0.196-0.819), 0.373(0.183-0.762), respectively. Participants who had hair permed and dyed during pregnancy had higher urinary level of MBP and MBzP, OR (95% CI) were 12.867 (1.240-133.525), 15.982 (1.367-186.911), respectively; Participants who use cosmetics during pregnancy had higher urinary level of MEP and MBP, OR (95% CI) were 2.977 (1.012-8.757), 4.440 (1.485-13.272), respectively; plastic bottled water consumption was positively associated with urinary concentrations of MEP and MEHP, OR (95% CI) were 3.780 (1.417-10.083), 2.699 (1.039-7.010), respectively; annual household income was negatively associated with urinary concentration of MMP, OR (95% CI) was 0.597 (0.372-0.959); individuals who took medications during pregnancy had higher urinary level of MEHP than non-takers, OR (95% CI) was 4.853 (1.084-21.732). CONCLUSION: Pregnant women whose gestation age was less than 16 weeks are generally exposed to phthalate. Phthalate internal exposure levels are significantly associated with most measured factors and the influencing factors with different phthalates internal exposure levels are different. PMID- 26833013 TI - [Survey of physical activity and health among Chinese senior citizens over 70 years old]. AB - OBJECTIVE: To investigate characteristics of physical activities among Chinese senior citizens over 70 years old, and analyze the relationship between physical activities and health. METHODS: Using multistage stratified sampling method, 1 960 senior citizens over 70 years old were included in the investigation from 7 cities of 5 provinces in the northeast, east, center and west of China from March to September 2014. After removing missing samples, 1 420 samples were kept. Time duration, intensity, frequency and physical condition scores of each physical activities were obtained by using a questionnaire of physical activities and a simplified version of life quality scale (SF-12 scale). Physical condition scores of different groups with different genders and ages were analyzed by using t-test of two independent samples; and physical conditions of different physical activities were compared by chi(2)-test. RESULTS: Senior citizens did physical activities 6-7 times per week (79.2%, 1 125/1 420) with low and moderate intensity (41.6%, 591/1 420) for 0.5-1.0 hour per time (42.5%, 604/1 420). Total scores of senior citizen were (63.7 +/- 15.1), and health scores of men (67.3 +/- 14.8) were higher than those in women (60.1 +/- 17.8) (t = 8.31, P < 0.001). Health scores for the group with the age of 70-74 (69.5 +/- 14.6) were higher than those in the group of 80-84 and the group >= 85 (62.1 +/- 17.0, 57.3 +/- 17.9) (F were 2.53 and 3.02, respectively, P < 0.001). Health scores for the group with the age of 75-79 (66.0 +/- 16.9) were higher than those in the group >= 85 (57.3 +/- 17.9) (F = 2.47, P < 0.001). Total detection rates of senior citizen were (64.8%, 920/1 420), health detection rates for the groups with higher and medium physical activities (69.8%, 268/384) and (66.8%, 436/653) were both higher than those in the low group (56.4%, 216/383) (chi(2) were 14.78 and 11.13, respectively, P < 0.001). CONCLUSION: Senior citizens have physical activities quite frequently with low and medium intensity for a short time period. Health condition declines with age increases; physical health situations are better for men than those for women. Medium and high physical activities do good to health for senior citizens. PMID- 26833014 TI - [Colorimetric detection of coxsackievirus A6 by reverse transcription loop mediated isothermal amplification]. AB - OBJECTIVE: To develop a simple, rapid and sensitive colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) for rapid detection of coxsackievirus A6 (CV-A6) based on the colour chang of hydroxy naphthol blue (HNB). METHODS: The method employed a set of six primers that recognized sequences of VP1 gene for amplification of nucleic acid under isothermal conditions at 63 degrees C for 50 min. The products were detected through visual inspection of color change by the pre-addition of HNB dye. The specificity was validated by detecting a collection of different human enteroviruses. The sensitivity of this assay was evaluated by serial dilutions of RNA molecules from in vitro transcription of CV-A6 VP1 gene, and compared with real-time RT-PCR (rRT-PCR) in parallel. This assay was evaluated with 92 clinical specimens from patients with hand-foot-mouth disease. RESULTS: A positive color (sky blue) was only observed in the preparation of CV-A6, whereas none of the other 23 kinds of human enteroviruses showed a color change. The HNB based RT LAMP showed a sensitivity of 100 copies/reaction, which was at the same level as that of the rRT-PCR. The result of RT-LAMP in analysis of 92 clinical specimens was consistent with that of the rRT-PCR. The kappa correlation between the two methods was 1 and both of the sensitivity and specificity of the RT-LAMP assay were 100%. CONCLUSION: The established RT-LAMP assay had good specificity and sensitivity and thus demonstrated to be a promising screening tool for CV-A6 infection. It also has the potential to be used in resource-limited clinical sites and field study. PMID- 26833015 TI - [Impact factors related to HIV voluntary counseling and testing of pregnant women in Liangshan Yi Autonomous Prefecture, Sichuan]. PMID- 26833016 TI - [Sero-epidemiological study on hepatitis E of Xinjiang Uygur autonomous region in 2010-2012]. PMID- 26833017 TI - [Epidemiological and laboratory investigations on an infant case with diarrhea caused by salmonella enterica serovar typhimurium]. PMID- 26833018 TI - [Review on the association between social culture and HIV prevalence among MSM in China]. AB - Social culture have significant influence on HIV transmission. Men who have sex with men (MSM), have their own sub-culture, by which made them very different with other population in social norm, behavior mode, as well as some HIV related behavior and the disease transmission risk. Up to date, study focused on the association between social culture and HIV transmission among MSM was limited, thus we reviewed relevant studies in the view of social culture and sub-culture of MSM, analyzed how social culture could potentially influence HIV transmission, and how sub-culture could affect MSM's friend-making, HIV risk behaviors in three aspects including social identity, social norm and social development. Furthermore, we provided some recommendations and suggestions on the future work. PMID- 26833019 TI - Voluntary Medical Support Is Key After Nuclear Disasters. PMID- 26833020 TI - Evaluation of the enzymatic activity and stability of commercial bromelain incorporated in topical formulations. AB - BACKGROUND: Bromelain is a mixture of proteolytic enzymes found in various tissues of the pineapple plant (Ananas comosus) and other species of Bromeliaceae. Owing to its proteolytic activity, bromelain has been used in the food, medical, pharmaceutical and cosmetic industries, for its cell renewal, anti ageing, whitening and anti-cellulite properties. OBJECTIVE: This study evaluated the stability of bromelain (commercial powder) incorporated in topical formulations. METHODS: Bromelain was incorporated at three concentrations, 0.5%, 1.0% and 2.0%, in oil-in-water emulsion and gel, and stored for six months at varying stress conditions. Stability was accessed by measuring the changes in the protein content, enzymatic activity, viscosity, rheology, pH and colour of the selected formulations. RESULTS: The colour of all the samples changed after 180 days of incubation, indicating the concentration-dependence and temperature sensitive nature of these formulations. No relationship was observed between the changes in the pH, temperature and luminosity exposure in all the samples. Gels proved to be the least preferred base for incorporation of bromelain for use as a topical formulation, owing to its inability to maintain the integrity of bromelain, thereby affecting the formulation characteristics. CONCLUSION: The emulsion-based formulations at all the concentrations of bromelain were more stable than the gel-based formulation over 180 days of evaluation, at a temperature of 5 degrees C, protected from light. PMID- 26833021 TI - Problematic secondary health conditions among adults with spinal cord injury and its impact on social participation and daily life. AB - OBJECTIVE: This exploratory study describes the problematic secondary health conditions among adults with a spinal cord injury (SCI) and the impact these health concerns have on social participation and daily life. DESIGN: Cross sectional survey design. SETTING: A community-based rehabilitation program within the United States. PARTICIPANTS: Fifty-six adults (33 males and 23 females; age 18 to 73 [M = 39.4, SD = 12.7]) with SCI participating in the community-based rehabilitation program. METHODS: Subjects identified the top five problematic secondary health conditions related to his/her SCI, belief about the impact these conditions have on social participation and daily life, and if they believed the secondary health condition(s) were avoidable. RESULTS: The top problematic areas identified were bladder control, pain, bowel control, and pressure ulcers, and 73% felt these problems were unavoidable. In addition, more than 66% had each of these problems continuously during the last 12 months. When examining the impact of the problematic secondary health conditions, 75% identified that the primary problem had a significant impact on social participation and 64% identified it significantly impacted daily life. CONCLUSION: Although the majority of the participants were actively participating in a community-based rehabilitation wellness program, it appears that they thought engagement in social participation and daily life were negatively impacted by the secondary health conditions and unavoidable. The results suggested unfulfilled goals despite the emphasized efforts of medical providers to help manage the secondary conditions. Future research should examine why individuals with SCI still have a difficult time managing secondary health conditions. PMID- 26833022 TI - Dielectric singularity in hyperbolic metamaterials: the inversion point of coexisting anisotropies. AB - Hyperbolic Metamaterials are artificially engineered materials whose optical properties can be specifically tailored to manifest an extremely high level of anisotropy. Due to this remarkable anisotropy they represent a unique opportunity to realize effective bulk meta-structure with extraordinary optical properties in the visible range. A simultaneous dielectric singularity in the in plane permittivity, with respect to the propagation direction, has to lead to a complete sign inversion of the same permittivity for that specific visible frequency. Such a drastic phase change has been theoretically highlighted in the past as the major challenge to be overcome in order to unlock many remarkable optical properties not present artificial optical systems. In this paper we experimentally demonstrate the realization of a metal-dielectric multilayer structure showing an inversion point of coexisting anisotropies at a specified wavelength in the visible range, rising from the particular design and fabrication process. Theoretical models and numerical simulations are in very good agreement with experimental data. Ellipsometrical experiments and optical modeling demonstrate the drastic type I/type II transition. Supercollimation effect has been achieved at the inversion point of the coexisting extreme anisotropies, whereas at the epsilon near zero and pole frequency the perfect lens behavior has been observed. PMID- 26833023 TI - Streptomyces thermoautotrophicus does not fix nitrogen. AB - Streptomyces thermoautotrophicus UBT1 has been described as a moderately thermophilic chemolithoautotroph with a novel nitrogenase enzyme that is oxygen insensitive. We have cultured the UBT1 strain, and have isolated two new strains (H1 and P1-2) of very similar phenotypic and genetic characters. These strains show minimal growth on ammonium-free media, and fail to incorporate isotopically labeled N2 gas into biomass in multiple independent assays. The sdn genes previously published as the putative nitrogenase of S. thermoautotrophicus have little similarity to anything found in draft genome sequences, published here, for strains H1 and UBT1, but share >99% nucleotide identity with genes from Hydrogenibacillus schlegelii, a draft genome for which is also presented here. H. schlegelii similarly lacks nitrogenase genes and is a non-diazotroph. We propose reclassification of the species containing strains UBT1, H1, and P1-2 as a non Streptomycete, non-diazotrophic, facultative chemolithoautotroph and conclude that the existence of the previously proposed oxygen-tolerant nitrogenase is extremely unlikely. PMID- 26833024 TI - Correcting the NLRP3 inflammasome deficiency in macrophages from autoimmune NZB mice with exon skipping antisense oligonucleotides. AB - Inflammasomes are molecular complexes activated by infection and cellular stress, leading to caspase-1 activation and subsequent interleukin-1beta (IL-1beta) processing and cell death. The autoimmune NZB mouse strain does not express NLRP3, a key inflammasome initiator mediating responses to a wide variety of stimuli including endogenous danger signals, environmental irritants and a range of bacterial, fungal and viral pathogens. We have previously identified an intronic point mutation in the Nlrp3 gene from NZB mice that generates a splice acceptor site. This leads to inclusion of a pseudoexon that introduces an early termination codon and is proposed to be the cause of NLRP3 inflammasome deficiency in NZB cells. Here we have used exon skipping antisense oligonucleotides (AONs) to prevent aberrant splicing of Nlrp3 in NZB macrophages, and this restored both NLRP3 protein expression and NLRP3 inflammasome activity. Thus, the single point mutation leading to aberrant splicing is the sole cause of NLRP3 inflammasome deficiency in NZB macrophages. The NZB mouse provides a model for addressing a splicing defect in macrophages and could be used to further investigate AON design and delivery of AONs to macrophages in vivo. PMID- 26833025 TI - Two macrophage migration inhibitory factors regulate starfish larval immune cell chemotaxis. AB - Immune cell recruitment is critical step in the inflammatory response and associated diseases. However, the underlying regulatory mechanisms are poorly understood in invertebrates. Mesenchyme cells of the starfish larvae, which allowed Metchnikoff to complete his landmark experiments, are important model for analysis of immune cell migration. The present study investigated the role of macrophage migration inhibitory factor (MIF)--an evolutionarily conserved cytokine that is functionally similar to chemokines--in the larvae of the starfish Patiria (Asterina) pectinifera, which were found to possess two orthologs, ApMIF1 and ApMIF2. ApMIF1 and ApMIF2 clustered with mammalian MIF and its homolog D-dopachrome tautomerase (DDT), respectively, in the phylogenetic analysis. In contrast to the functional similarity between mammalian MIF and DDT, ApMIF1 knockdown resulted in the excessive recruitment of mesenchyme cells in vivo, whereas ApMIF2 deficiency inhibited the recruitment of these cells to foreign bodies. Mesenchyme cells migrated along a gradient of recombinant ApMIF2 in vitro, whereas recombinant ApMIF1 completely blocked ApMIF2-induced directed migration. Moreover, the expression patterns of ApMIF1 and ApMIF2 messenger RNA in bacteria-challenged mesenchyme cells were consistent with in vivo observations of cell behaviors. These results indicate that ApMIF1 and ApMIF2 act as chemotactic inhibitory and stimulatory factors, respectively, and coordinately regulate mesenchyme cell recruitment during the immune response in starfish larvae. This is the first report describing opposing functions for MIF- and DDT like molecules. Our findings provide novel insight into the mechanisms underlying immune regulation in invertebrates. PMID- 26833029 TI - Upregulation of PI3K/AKT/mTOR, FABP5 and PPARbeta/delta in Human Psoriasis and Imiquimod-induced Murine Psoriasiform Dermatitis Model. PMID- 26833026 TI - Intestinal Phospholipid Remodeling Is Required for Dietary-Lipid Uptake and Survival on a High-Fat Diet. AB - Phospholipids are important determinants of membrane biophysical properties, but the impact of membrane acyl chain composition on dietary-lipid absorption is unknown. Here we demonstrate that the LXR-responsive phospholipid-remodeling enzyme Lpcat3 modulates intestinal fatty acid and cholesterol absorption and is required for survival on a high-fat diet. Mice lacking Lpcat3 in the intestine thrive on carbohydrate-based chow but lose body weight rapidly and become moribund on a triglyceride-rich diet. Lpcat3-dependent incorporation of polyunsaturated fatty acids into phospholipids is required for the efficient transport of dietary lipids into enterocytes. Furthermore, loss of Lpcat3 amplifies the production of gut hormones, including GLP-1 and oleoylethanolamide, in response to high-fat feeding, contributing to the paradoxical cessation of food intake in the setting of starvation. These results reveal that membrane phospholipid composition is a gating factor in passive lipid absorption and implicate LXR-Lpcat3 signaling in a gut-brain feedback loop that couples absorption to food intake. PMID- 26833030 TI - Developing a Patient-Centered Radiology Process Model. AB - PURPOSE: There has been increasing interest in the process of care that patients experience. To keep step with the rest of medicine, our specialty should be designing metrics that assess the overall experience of patients seeking care in radiology departments. A recent memo from the ACR chair calls for more work in this area. The aim of this study was to develop a patient-centered model for the experience of radiologic care, which may be helpful in addressing this need. METHODS: Using principles of multiattribute utility theory and psychometric theory as well as recent literature, a model was developed for a patient-centered index that could be used in radiology facilities. RESULTS: A model was developed that concisely incorporates patient-centeredness of both radiologists and staff members (communication with patient and referrers, competence, and pain control) as well as patient- and process-related issues such as costs, procedural morbidity, access to care, appointment duration, waiting, timing of appointments, cleanliness of facility, and coordination with clinical services. The overall radiology process model was constructed as a set of nested models, which allow more integrated detail within the domains of patient experience. CONCLUSIONS: This model and others like it may help the ACR develop quality metrics to reasonably quantify the patient experience. PMID- 26833032 TI - Probing atomic positions of adsorbed ammonia molecules in zeolite. AB - Atomic positions and interactions between adsorbed guest molecules, such as ammonia in H-ZSM-5 microporous solids, are for the first time revealed by making use of the change in the periodical scattering parameter using in situ synchrotron powder X-ray diffraction combined with refinement within experimental errors. PMID- 26833031 TI - Phylogenetic analysis and protein structure modelling identifies distinct Ca(2+)/Cation antiporters and conservation of gene family structure within Arabidopsis and rice species. AB - BACKGROUND: The Ca(2+)/Cation Antiporter (CaCA) superfamily is an ancient and widespread family of ion-coupled cation transporters found in nearly all kingdoms of life. In animals, K(+)-dependent and K(+)-indendent Na(+)/Ca(2+) exchangers (NCKX and NCX) are important CaCA members. Recently it was proposed that all rice and Arabidopsis CaCA proteins should be classified as NCX proteins. Here we performed phylogenetic analysis of CaCA genes and protein structure homology modelling to further characterise members of this transporter superfamily. FINDINGS: Phylogenetic analysis of rice and Arabidopsis CaCAs in comparison with selected CaCA members from non-plant species demonstrated that these genes form clearly distinct families, with the H(+)/Cation exchanger (CAX) and cation/Ca(2+) exchanger (CCX) families dominant in higher plants but the NCKX and NCX families absent. NCX-related Mg(2+)/H(+) exchanger (MHX) and CAX-related Na(+)/Ca(2+) exchanger-like (NCL) proteins are instead present. Analysis of genomes of ten closely-related rice species and four Arabidopsis-related species found that CaCA gene family structures are highly conserved within related plants, apart from minor variation. Protein structures were modelled for OsCAX1a and OsMHX1. Despite exhibiting broad structural conservation, there are clear structural differences observed between the different CaCA types. CONCLUSIONS: Members of the CaCA superfamily form clearly distinct families with different phylogenetic, structural and functional characteristics, and therefore should not be simply classified as NCX proteins, which should remain as a separate gene family. PMID- 26833033 TI - Performance trends in master freestyle swimmers aged 25-89 years at the FINA World Championships from 1986 to 2014. AB - Performance trends in elite freestyle swimmers are well known, but not for master freestyle swimmers. We investigated trends in participation, performance, and sex difference in performance of 65,584 freestyle master swimmers from 25-29 to 85-89 years competing in FINA World Masters Championships between 1986 and 2014. The men-to-women ratio was calculated for each age group, and the trend across age groups was analyzed using single linear regression analysis. Trends in performance changes were investigated using a mixed-effects regression model with sex, distance, and calendar year as fixed variables. Participation increased in women and men in older age groups (i.e., 40 years and older). Women and men improved race times across years in all age groups and distances. For age groups 25-29 to 75-79 years, women were slower than men, but not for age groups 80-84 to 85-89 years. In 50, 100, and 200 m, women reduced the sex difference from 1986 to 2014 in age groups 30-34 to 75-79 years. In 400 m, women reduced the gap to men across time in age groups 40-44, 45-49, and 55-59 years. In 800 m, sex difference became reduced across time in age groups 55-59 and 70-74 years. In summary, participation increased from 1986 to 2014 in women and men in older age groups, women and men improved across time performance in all distances, and women were not slower compared to men in age groups 80-84 to 85-89 years. We expect a continuous trend in increasing participation and improved performance in master freestyle swimmers. PMID- 26833034 TI - The relationship between hippocampal volume and static postural sway: results from the GAIT study. AB - The role of the hippocampus in postural control, in particular in maintaining upright stance, has not been fully examined in normal aging. This study aims to examine the association of postural sway with hippocampal volume while maintaining upright stance in healthy older individuals. Seventy healthy individuals (mean age 69.7 +/- 3.4 years; 41.4 % women) were recruited in this study based on cross-sectional design. Hippocampal volume (quantified from a three-dimensional T1-weighted MRI using semi-automated software), three center of pressure (COP) motion parameters (sway area, path length of anterior-posterior (AP) and medial-lateral (ML) displacement) while maintaining upright stance (eyes open and closed), and the relative difference between open and closed eye conditions were used as outcome measures. Age, sex, body mass index, lower limb proprioception, distance vision, 15-item geriatric depression scale score, total cranial volume, and white matter abnormalities were used as covariates. The sway area decreased from open to closed eye condition but this variation was non significant (P = 0.244), whereas path length of AP and ML displacement increased significantly (P < 0.003). Increase in sway area from open to closed eyes was associated with greater hippocampal volume (beta -18.21; P = 0.044), and a trend for an association of increase in path length of AP displacement (P = 0.075 for open eyes and P = 0.071 for closed eyes) with greater hippocampal volume was reported. The hippocampus is involved in upright postural control in normal aging, such that an increase in sway area of COP motion from open to closed eyes is associated with greater hippocampal volume in healthy older adults. PMID- 26833036 TI - Real-Time Monitoring of Singlet Oxygen and Oxygen Partial Pressure During the Deep Photodynamic Therapy In Vitro. AB - Photodynamic therapy (PDT) is an effective noninvasive method for the tumor treatment. The major challenge in current PDT research is how to quantitatively evaluate therapy effects. To our best knowledge, this is the first time to combine multi-parameter detection methods in PDT. More specifically, we have developed a set of system, including the high-sensitivity measurement of singlet oxygen, oxygen partial pressure and fluorescence image. In this paper, the detection ability of the system was validated by the different concentrations of carbon quantum dots. Moreover, the correlation between singlet oxygen and oxygen partial pressure with laser irradiation was observed. Then, the system could detect the signal up to 0.5 cm tissue depth with 660 nm irradiation and 1 cm tissue depth with 980 nm irradiation by using up-conversion nanoparticles during PDT in vitro. Furthermore, we obtained the relationship among concentration of singlet oxygen, oxygen partial pressure and tumor cell viability under certain conditions. The results indicate that the multi-parameter detection system is a promising asset to evaluate the deep tumor therapy during PDT. Moreover, the system might be potentially used for the further study in biology and molecular imaging. PMID- 26833037 TI - Evaluation of Physiological Control Systems for Rotary Left Ventricular Assist Devices: An In-Vitro Study. AB - Rotary left ventricular assist devices (LVADs) show weaker response to preload and greater response to afterload than the native heart. This may lead to ventricular suction or pulmonary congestion, which can be deleterious to the patient's recovery. A physiological control system which optimizes responsiveness of LVADs may reduce adverse events. This study compared eight physiological control systems for LVAD support against constant speed mode. Pulmonary (PVR) and systemic (SVR) vascular resistance changes, a passive postural change and exercise were simulated in a mock circulation loop to evaluate the controller's ability to prevent suction and congestion and to increase exercise capacity. Three active and one passive control systems prevented ventricular suction at high PVR (500 dyne s cm(-5)) and low SVR (600 dyne s cm(-5)) by decreasing LVAD speed (by 200-515 rpm) and by increasing LVAD inflow cannula resistance (up to 1000 dyne s cm(-5)) respectively. These controllers increased LVAD preload sensitivity (to 0.196-2.415 L min(-1) mmHg(-1)) compared to the other control systems and constant speed mode (0.039-0.069 L min(-1) mmHg(-1)). The same three active controllers increased pump speed (600-800 rpm) and thus LVAD flow by 4.5 L min(-1) during exercise which increased exercise capacity. Physiological control systems that prevent adverse events and/or increase exercise capacity may help improve LVAD patient conditions. PMID- 26833038 TI - Mastoid Vibration Affects Dynamic Postural Control During Gait. AB - Our objective was to investigate how manipulating sensory input through mastoid vibration (MV) could affect dynamic postural control during walking, with and without simultaneous manipulation of the visual and the somatosensory systems. We used three levels of MV (none, unilateral, and bilateral) via vibrating elements placed on the mastoid processes. We combined this with the six conditions of the Locomotor Sensory Organization Test (LSOT) paradigm to challenge the visual and somatosensory systems. We hypothesized that MV would affect both amount and temporal structure measures of sway variability during walking and that, in combination with manipulations of the visual and the somatosensory inputs, MV would augment the effects previously observed. The results confirmed that MV produced a significant increase in the amount of sway variability in both anterior-posterior and medial-lateral directions. Significant changes in the temporal structure of sway variability were only observed in the anterior posterior direction. Bilateral MV produced larger effects than unilateral stimulation. We concluded that sensory input while walking could be affected using MV. Combining MV with manipulations of visual and somatosensory input could allow us to better understand the contributions of the sensory systems during locomotion. PMID- 26833039 TI - A Simple fMRI Compatible Robotic Stimulator to Study the Neural Mechanisms of Touch and Pain. AB - This paper presents a simple device for the investigation of the human somatosensory system with functional magnetic imaging (fMRI). PC-controlled pneumatic actuation is employed to produce innocuous or noxious mechanical stimulation of the skin. Stimulation patterns are synchronized with fMRI and other relevant physiological measurements like electroencephalographic activity and vital physiological parameters. The system allows adjustable regulation of stimulation parameters and provides consistent patterns of stimulation. A validation experiment demonstrates that the system safely and reliably identifies clusters of functional activity in brain regions involved in the processing of pain. This new device is inexpensive, portable, easy-to-assemble and customizable to suit different experimental requirements. It provides robust and consistent somatosensory stimulation, which is of crucial importance to investigating the mechanisms of pain and its strong connection with the sense of touch. PMID- 26833040 TI - Evaluating Harms in the Assessment of Net Benefit: A Framework for Newborn Screening Condition Review. AB - BACKGROUND: The Department of Health and Human Services (HHS) Advisory Committee on Heritable Disorders in Newborns and Children ("Advisory Committee") makes recommendations to the HHS Secretary regarding addition of new conditions to the national Recommended Uniform Screening Panel for newborns. The Advisory Committee's decision-making process includes assessing the net benefit of screening for nominated conditions, informed by systematic evidence reviews generated by an independent Condition Review Workgroup. The evidence base regarding harms associated with screening for specific conditions is often more limited than that for benefits. PROCEDURES: The process for defining potential harms from newborn screening reviewed the frameworks from other public health evidence-based review processes, adapted to newborn screening by experts in systematic review, newborn screening programs and bioethics, with input from and approval by the Advisory Committee. MAIN FINDINGS: To support the Advisory Committee's review of nominated conditions, the Workgroup has developed a standardized approach to evaluation of harms and relevant gaps in the evidence. Types of harms include the physical burden to infants; psychosocial and logistic burdens to families from screening or diagnostic evaluation; increased risk of medical treatment for infants diagnosed earlier than children with clinical presentation; delayed diagnosis from false negative results; psychosocial harm from false positive results; uncertainty of clinical diagnosis, age of onset or clinical spectrum; and disparities in access to diagnosis or therapy. CONCLUSIONS: Estimating the numbers of children at risk, the magnitude, timing and likelihood of harms will be integrated into Workgroup reports to the Advisory Committee. PMID- 26833041 TI - Measurement of epicardial fat thickness by transthoracic echocardiography for predicting high-risk coronary artery plaques. AB - Epicardial adipose tissue (EAT) volume is reported to be associated with coronary plaques. We evaluated whether non-invasive measurement of EAT thickness by echocardiography can predict high-risk coronary plaque characteristics determined independently by coronary computed tomography (CT) angiography. We enrolled 406 patients (mean age 63 years, 57 % male) referred for 64-slice CT. EAT was measured on the right ventricle free wall from a parasternal long-axis view at the end of systole. High-risk coronary plaques were defined as low-density plaques (<30 Hounsfield units) with positive remodeling (remodeling index >1.05). Patients were divided into thin or thick EAT groups using a cutoff value derived from receiver operator characteristic curve analysis for discriminating high-risk plaques. The receiver operator characteristic cutoff value was 5.8 mm with a sensitivity of 83 % and specificity of 64 % (area under the curve 0.77, 95 % confidence interval 0.70-0.83, p < 0.01). Compared with the thin EAT group, the thick EAT group had a high prevalence of low-density plaques (4 vs. 24 %, p < 0.01), positive remodeling (39 vs. 60 %, p < 0.01), and high-risk plaques (3 vs. 17 %, p < 0.01). Multiple logistic analysis revealed that thick EAT was a significant predictor of high-risk plaques (odds ratio 7.98, 95 % confidence interval 2.77-22.98, p < 0.01) after adjustment for covariates, including conventional risk factors, visceral adipose tissue area, and medications. The measurement of EAT thickness by echocardiography may provide a non-invasive option for predicting high-risk coronary plaques. PMID- 26833042 TI - Repetitive restriction of muscle blood flow enhances mTOR signaling pathways in a rat model. AB - Skeletal muscle is a plastic organ that adapts its mass to various stresses by affecting pathways that regulate protein synthesis and degradation. This study investigated the effects of repetitive restriction of muscle blood flow (RRMBF) on microvascular oxygen pressure (PmvO2), mammalian target of rapamycin (mTOR) signaling pathways, and transcripts associated with proteolysis in rat skeletal muscle. Eleven-week-old male Wistar rats under anesthesia underwent six RRMBF consisting of an external compressive force of 100 mmHg for 5 min applied to the proximal portion of the right thigh, each followed by 3 min rest. During RRMBF, PmvO2 was measured by phosphorescence quenching techniques. The total RNA and protein of the tibialis anterior muscle were obtained from control rats, and rats treated with RRMBF 0-6 h after the stimuli. The protein expression and phosphorylation of various signaling proteins were determined by western blotting. The mRNA expression level was measured by real-time RT-PCR analysis. The total muscle weight increased in rats 0 h after RRMBF, but not in rats 1-6 h. During RRMBF, PmvO2 significantly decreased (36.1 +/- 5.7 to 5.9 +/- 1.7 torr), and recovered at rest period. RRMBF significantly increased phosphorylation of p70 S6-kinase (p70S6k), a downstream target of mTOR, and ribosomal protein S6 1 h after the stimuli. The protein level of REDD1 and phosphorylation of AMPK and MAPKs did not change. The mRNA expression levels of FOXO3a, MuRF-1, and myostatin were not significantly altered. These results suggested that RRMBF significantly decreased PmvO2, and enhanced mTOR signaling pathways in skeletal muscle using a rat model, which may play a role in diminishing muscle atrophy under various conditions in human studies. PMID- 26833044 TI - Migrant breast cancer patients and their participation in genetic counseling: results from a registry-based study. AB - Certain ethnic groups seem to have less access to cancer genetic counseling. Our study was to investigate the participation in cancer genetic counseling among migrant breast cancer patients of Turkish and Moroccan origin. Hospital medical records of Turkish and Moroccan and of a comparative group of non Turkish/Moroccan newly diagnosed breast cancer patients were studied. All women were diagnosed between 2007 and 2012. Eligibility for genetic counseling was assessed with a checklist. A total of 156 Turkish/Moroccan patients were identified, and 321 patients were assigned to the comparative group. About one third (35%) of the Turkish/Moroccan patients fulfilled criteria for breast cancer genetic counseling, compared to 21% of the comparative group (P = 0.001); this was largely due to a relatively young age at diagnosis in the migrant group (26% <40 years vs 5% in the comparative group, P = 0.0001). Uptake of genetic counseling among eligible patients was 47% in the migrant group and 56% in the comparative group; differences in uptake were seen among the patients diagnosed before 40 years of age (48% in the migrant group vs 81% in the comparative group; P = 0.021). When adjusted for age at diagnosis, ethnicity was associated with discussing referral to genetic counseling and its actual uptake. The Turkish/Moroccan ethnicity appears to be associated with a lower uptake of genetic counseling, mainly caused by the lower uptake in the young age-group. The major barrier to participation in genetic counseling seems to lie within the referral process. PMID- 26833043 TI - Ovarian cancer patients at high risk of BRCA mutation: the constitutional genetic characterization does not change prognosis. AB - Ovarian neoplasms secondary to germline BRCA mutations had been described to have a more favourable survival. There is only few data concerning the prognosis of non mutated patients presenting clinical features evocative of BRCA alterations. We retrospectively collected data from patients treated in our institution for an invasive ovarian carcinoma between 1995 and 2011. Patients considered at high risk of BRCA mutation were tested for BRCA1/2 germline mutations. We described clinical, pathological and therapeutic features and compared prognosis of BRCA mutation carriers and non-mutated patients. Out of 617 ovarian cancer patients, we identified 104 patients who were considered at high risk of mutation. The 33 mutated patients were more likely to present a personal (33 vs. 10 %, p = 0.003) or a family (42 vs. 24 %, p = 0.06) history of breast/ovarian cancers. BRCA1/2 mutation carriers and wild type patients displayed similar prognosis: median progression-free survival (PFS) of 20.9 versus 37.7 months (p = 0.21); median overall survival (OS) of 151.2 versus 122.5 months (p = 0.52). Personal history of breast cancer increased both PFS [HR = 0.45 (95CI 0.25-0.81)] and OS [HR = 0.35 (95CI 0.16-0.75)]. In multivariate analysis, this parameter was an independent prognostic feature, whereas the identification of a BRCA1/2 mutation was not. In our cohort, all patients at high risk of BRCA mutation share a similar prognosis, whatever is their germline mutation status. Prognosis seems to be more influenced by clinical history than by germline mutations identification. If it is confirmed in larger and independent series, this result suggests that the hypothesis of other BRCA pathway alterations (BRCAness phenotype) deserves to be deeply explored. PMID- 26833045 TI - A mutation of the succinate dehydrogenase B gene in a Korean family with paraganglioma. AB - Familial paraganglioma (PGL) is a dominantly inherited disorder characterized by development of PGLs in the head and neck region. Germline mutations in genes coding for succinate dehydrogenase (SDH) subunits D, B, and C (SDHD, SDHB, SDHC) are found in almost all familial PGL patients. A 19-year-old female presented with pulsatile tinnitus and a reddish pulsating mass in the external auditory canal, and her mother complained of similar symptoms. Paraganglioma was found in both patients and was surgically removed. We report a case of germline SDHB mutation. This mutation was a deletion of thymine at nucleotide position 757 in exon 7 of the SDHB gene (c.757delT). PMID- 26833046 TI - BRCA1/BRCA2 founder mutations and cancer risks: impact in the western Danish population. AB - Mutations in the BRCA1 and BRCA2 genes significantly contribute to hereditary breast cancer and ovarian cancer, but the phenotypic effect from different mutations is insufficiently recognized. We used a western Danish clinic-based cohort of 299 BRCA families to study the female cancer risk in mutation carriers and their untested first-degree relatives. Founder mutations were characterized and the risk of cancer was assessed in relation to the specific mutations. In BRCA1, the cumulative cancer risk at age 70 was 35 % for breast cancer and 29 % for ovarian cancer. In BRCA2, the cumulative risk was 44 % for breast cancer and 15 % for ovarian cancer. We identified 47 distinct BRCA1 mutations and 48 distinct mutations in BRCA2. Among these, 8 founder mutations [BRCA1 c.81 ?_4986+?del, c.3319G>T (p.Glu1107*), c.3874delT and c.5213G>A (p.Gly1738Glu) and BRCA2 c.6373delA, c.7008-1G>A, c.7617+1G>A and c.8474delC] were found to account for 23 % of the BRCA1 mutations and for 32 % of the BRCA2 mutations. The BRCA1 mutation c.3319G>T was, compared to other BRCA1 mutations, associated with a higher risk for ovarian cancer. In conclusion, founder mutations in BRCA1 and BRCA2 contribute to up to one-third of the families in western Denmark and among these the BRCA1 c.3319G>T mutation is potentially linked to an increased risk of ovarian cancer. PMID- 26833047 TI - An Information Theoretical Study of the Epistasis Between the CNR1 1359 G/A Polymorphism and the Taq1A and Taq1B DRD2 Polymorphisms: Assessing the Susceptibility to Cannabis Addiction in a Turkish Population. AB - Addiction is a complex, multi-factorial disease, and thus, analyzing genetic variants at multiple loci and gene-gene interactions among them (epistasis) can provide crucial clues about causative factors of addiction which cannot be detected with single-nucleotide polymorphism (SNP) association studies. In this study, we discuss the interaction between the 1359 G/A polymorphism of the CNR1 gene and the DRD2 gene polymorphisms and the net effect of any possible epistasis on the cannabis addiction phenotype in a Turkish population. Using bivariate synergy and mutual information concepts as a means of capturing the magnitude of interaction between marker pairs, the present study not only confirms the A1 marker allele as a risk factor but also reveals a finer-grained association between A and B markers which manifests itself both as a preventive and a risk factor. Our results indicate that the increased phenotype of cases require an individual to be either heterozygous at both loci or homozygous at locus B with homozygous risk factor A1A1 present. We hypothesize that overlapping expressions of CB1 and D2R is the cause of CB1-D2R interactions in cases of substance abuse and the different polymorphisms of CNR1 and DRD2 genes may have decisive roles in the nature of these interactions in terms of promoting or alleviating the cannabis addiction risk factor of the individual. PMID- 26833048 TI - Vivid: How valence and arousal influence word processing under different task demands. AB - In this study, we used event-related potentials to examine how different dimensions of emotion-valence and arousal-influence different stages of word processing under different task demands. In two experiments, two groups of participants viewed the same single emotional and neutral words while carrying out different tasks. In both experiments, valence (pleasant, unpleasant, and neutral) was fully crossed with arousal (high and low). We found that the task made a substantial contribution to how valence and arousal modulated the late positive complex (LPC), which is thought to reflect sustained evaluative processing (particularly of emotional stimuli). When participants performed a semantic categorization task in which emotion was not directly relevant to task performance, the LPC showed a larger amplitude for high-arousal than for low arousal words, but no effect of valence. In contrast, when participants performed an overt valence categorization task, the LPC showed a large effect of valence (with unpleasant words eliciting the largest positivity), but no effect of arousal. These data show not only that valence and arousal act independently to influence word processing, but that their relative contributions to prolonged evaluative neural processes are strongly influenced by the situational demands (and by individual differences, as revealed in a subsequent analysis of subjective judgments). PMID- 26833049 TI - The dynamic influence of emotional words on sentence comprehension: An ERP study. AB - In the present study, we explored the influence of emotional words on the semantic integration of their following neutral nouns during sentence comprehension. We manipulated the emotionality of verbs and the semantic congruity of their following (neutral) object nouns in sentences. Event-related potentials were recorded to the verbs, which were either negative or neutral, and to the object nouns, which were either semantically congruent or incongruent relative to the preceding contexts. We found an N400 and a P600 effect in response to the semantic congruity of the nouns when they followed the neutral verbs. However, the P600 (but not the N400) semantic congruity effect may have been attenuated when the nouns followed the negative verbs. Meanwhile, the negative verbs elicited a larger P2 and N400 than did the neutral verbs. The results indicate that the attention captured by emotional words impaired reanalysis of the following incongruent information, demonstrating a dynamic influence of emotional words on the semantic processing of following information during sentence comprehension. PMID- 26833050 TI - The effect of systemic corticosteroids on the innate and adaptive immune system in children with steroid responsive nephrotic syndrome. AB - The severity and duration of immunosuppression caused by corticosteroids (CSs) usage have not been extensively studied. We aimed to investigate the effects of CSs on the various compartments of immune system in relation to timing of initiation and persistence of therapy. Pediatric patients with idiopathic nephrotic syndrome (NS) treated with 2 mg/kg/day prednisolone and healthy control (HC) were enrolled. Blood samples were drawn for immunologic analyses at baseline and at the first and second weeks and first, second, and third months of CS therapy in addition to first and second weeks and first, second, and third months of discontinuation. Fourteen patients (M/F, 7/7) between 1 and 8 years old were evaluated. Untreated NS exhibited high absolute lymphocyte count (ALC)(p = 0.010), absolute CD3(+) T cells (p = 0.020) and absolute CD8(+) T cells (p = 0.006) compared to HC. Suppression in ALC was observed and nadir value was noted at first month of therapy compared to baseline (p = 0.002). The CD4(+) (p = 0.036) and CD8(+) T cell (p = 0.013) counts decreased significantly at the first week of treatment compared to baseline. While baseline B cell counts was indifferent from HC, gradually increased in 2 weeks of CS initiation and decreased during the treatment with a statistical significance compared to HC (p = 0.010). However, after cessation of CS, B cell counts continued to decline and found to be significantly different than baseline at first week (p = 0.008) and at third month (p = 0.040). CONCLUSION: Apart from baseline lymphocyte subset changing observed in untreated NS patients, our data implies that T cells were suppressed very early in the CS treatment. Interestingly, depressed B cell counts were detected later but persisted even after CS cessation. Due to early decrease in T cells, it would be beneficial to assume the patients as immunosuppressed at the very beginning of CS treatment to avoid infections. WHAT IS KNOWN: * Corticosteroids (CSs) are widely used for a variety of diseases including nephrotic syndrome, which is related with complex immune disturbance including T and B cells dysfunctions. * CSs induce neutrophilic leukocytosis concomitant with lymphopenia and eosinopenia leading to immunosupression. What is New: * T cell subsets and proliferation are susceptible to CSs more than B cells; however, the reversibility is faster with dose reduction in CS. * The change of B cells and B cell subtypes (CD27 (+) memory) shows prolonged effect of CSs on B cells which may alter antibody production even after 3 months of CSs cessation. PMID- 26833051 TI - Sleep in children with attention-deficit/hyperactivity disorder (ADHD) before and after 6-month treatment with methylphenidate: a pilot study. AB - Children with ADHD may present with sleep disturbances that add to the impairment of the disorder. The long-term sleep effects of the first-line pharmacological treatment for ADHD, i.e., psychostimulants, are unclear. In this pilot study, we compared polysomnographic variables in children with ADHD (n = 11, aged 6-15 years), before pharmacological treatment, and in children without ADHD (n = 22, aged 5-14 years); we also assessed polysomnographic changes in children with ADHD (n = 7) after a 6-month treatment with methylphenidate immediate-release (once or twice daily). Compared to children without ADHD, those with ADHD at baseline presented with significantly increased duration of awakenings (p = 0.02), reduction in sleep efficiency (p = 0.03), and increase in stage I (N1) (p < 0.01) and reduction in stage II (N2) (p = 0.02) and stage III-IV (N3) percentages. Methylphenidate treatment did not significantly change any parameter of sleep architecture. CONCLUSION: Preliminary evidence from this pilot study shows that, compared to children without ADHD, those with ADHD presented a more fragmented and less effective sleep at baseline and that the 6-month methylphenidate treatment did not further negatively impact on sleep architecture. WHAT IS KNOWN: * Children with ADHD may present with subjectively reported and/or objectively confirmed disturbances of sleep. * The long-term effects on sleep of the first line pharmacological treatment for ADHD, i.e., psychostimulants, are not clear. What is new: * Our study showed that the 6-month continuous treatment with methylphenidate did not further negatively impact on sleep architecture in children with ADHD. PMID- 26833052 TI - Genetic variants of ADAM17 are implicated in the pathological process of Kawasaki disease and secondary coronary artery lesions via the TGF-beta/SMAD3 signaling pathway. AB - Kawasaki disease (KD) is a systemic vasculitis childhood disease frequently complicating coronary artery lesions (CALs). Recently, the gene encoding a disintegrin and metalloprotease 17 (ADAM17) was found to modify vascular pathology in humans by differentially regulating the transforming growth factor beta (TGF-beta) signaling pathway, which affects KD/CAL susceptibility. To explore the potential role of ADAM17 in KD occurrence and outcomes, we investigated the association of 28 single nucleotide polymorphisms (SNPs) in ADAM17 and three pathway genes of TGF-beta signaling with KD phenotypes in a Han Chinese population, including 392 KD patients and 421 non-KD controls. Three ADAM17 SNPs showed an association with KD risk, which was further confirmed by haplotype analysis. The effect of ADAM17 on KD was also shown by multi-variable logistic regression analysis. In two-locus model analyses with SNPs in ADAM17 and TGF-beta signaling pathway genes, stronger compound effects on the risk of KD and secondary CAL formation were observed relative to comparable single SNPs. CONCLUSION: Our results suggest that ADAM17 contributes to the KD risk and is involved in secondary CAL formation via the TGF-beta/SMAD3 signaling pathway. This further enriches our understanding of the importance of the signaling pathway in KD occurrence and outcomes. WHAT IS KNOWN: * The transforming growth factor (TGF)-beta/SMAD3 signaling pathway greatly influences susceptibility to Kawasaki disease (KD) and secondary coronary artery lesions (CALs) and/or the treatment response of intravenous immunoglobulin. * A disintegrin and metalloprotease 17 (ADAM17) effectively reduces TGF-beta signaling by cleaving TGF-beta receptor type-1, while ADAM17 genetic variants modify human vascular pathology by differentially regulating this signaling although it is unknown whether ADAM17 contributes to KD phenotypes. What is New: * ADAM17 genetic variants were shown to be associated with KD risk, even when excluding the influence of TGF-beta signaling pathway genes, suggesting that ADAM17 is an important KD susceptibility-related genetic locus. * The more significant compound effects of two-locus models, combining single nucleotide polymorphisms (SNPs) in ADAM17 and other TGF-beta signaling pathway genes including TGFB2 and SMAD3, on KD phenotypes relative to single SNPs suggest that ADAM17 is also involved in secondary CAL formation and confers the risk of KD/CALs via the TGF beta/SMAD3 signaling pathway. PMID- 26833054 TI - Bone transport for the management of severely comminuted fractures without bone loss. AB - This study aims to provide a new method for treatment of severely comminuted fractures without bone loss using the well-known technique of bone transport. Sixteen patients suffering from severely comminuted fractures with closed soft tissue injury were prospectively treated using bone transport by Ilizarov circular fixator. There were 14 male and 2 female patients. The mean age was 36.5 years (27-45). There were 13 proximal tibial metaphyseal fractures, one tibial diaphyseal fracture and two femoral distal metaphyseal fractures. All patients had closed soft tissue. The mean length of the comminution gap was 50.3 mm (40 64). Fracture healing occurred in 15 patients. The mean healing time was 23.4 weeks (14-30). No bone stimulating procedures were needed for either the fracture or distraction site. Using the IOWA knee and ankle score for assessment of the 15 patients who completed treatment: the functional outcome for the knee was excellent in 11 patients, good in three and fair in one. The ankle score was excellent in 12 patients, good in two and fair in one. According to Paley and Maar's, bone results were excellent in 14 patients, good in one patient and poor in the patient who had failure of the procedure. The results achieved in this work are encouraging to keep on applying this technique to treat fractures that meet the following criteria: metaphyseal, with total circumferential comminution involving more than 4 cm of the bone length. PMID- 26833053 TI - On the computational assessment of white matter hyperintensity progression: difficulties in method selection and bias field correction performance on images with significant white matter pathology. AB - INTRODUCTION: Subtle inhomogeneities in the scanner's magnetic fields (B0 and B1) alter the intensity levels of the structural magnetic resonance imaging (MRI) affecting the volumetric assessment of WMH changes. Here, we investigate the influence that (1) correcting the images for the B1 inhomogeneities (i.e. bias field correction (BFC)) and (2) selection of the WMH change assessment method can have on longitudinal analyses of WMH progression and discuss possible solutions. METHODS: We used brain structural MRI from 46 mild stroke patients scanned at stroke onset and 3 years later. We tested three BFC approaches: FSL-FAST, N4 and exponentially entropy-driven homomorphic unsharp masking (E(2)D-HUM) and analysed their effect on the measured WMH change. Separately, we tested two methods to assess WMH changes: measuring WMH volumes independently at both time points semi automatically (MCMxxxVI) and subtracting intensity-normalised FLAIR images at both time points following image gamma correction. We then combined the BFC with the computational method that performed best across the whole sample to assess WMH changes. RESULTS: Analysis of the difference in the variance-to-mean intensity ratio in normal tissue between BFC and uncorrected images and visual inspection showed that all BFC methods altered the WMH appearance and distribution, but FSL-FAST in general performed more consistently across the sample and MRI modalities. The WMH volume change over 3 years obtained with MCMxxxVI with vs. without FSL-FAST BFC did not significantly differ (medians(IQR)(with BFC) = 3.2(6.3) vs. 2.9(7.4)ml (without BFC), p = 0.5), but both differed significantly from the WMH volume change obtained from subtracting post-processed FLAIR images (without BFC)(7.6(8.2)ml, p < 0.001). This latter method considerably inflated the WMH volume change as subtle WMH at baseline that became more intense at follow-up were counted as increase in the volumetric change. CONCLUSIONS: Measurement of WMH volume change remains challenging. Although the overall volumetric change was not significantly affected by the application of BFC, these methods distorted the image intensity distribution affecting subtle WMH. Subtracting the FLAIR images at both time points following gamma correction seems a promising technique but is adversely affected by subtle WMH. It is important to take into account not only the changes in volume but also in the signal intensity. PMID- 26833055 TI - Pregnancy rate in dairy cows treated with progesterone for six days during estrus synchronization with PGF2alpha. AB - The present study evaluated the effect of progesterone supplementation during a double PGF2alpha injection synchronization protocol on pregnancy per artificial insemination (P/AI) and on the incidence of twin births. Seven hundred and eighty three dairy cows were synchronized with two injections of PGF2alpha 14 days apart, starting on day 35 postpartum for their first postpartum insemination. Six days before the second PGF2alpha injection, cows were treated either with a progesterone-releasing intravaginal device (PRID-Delta) and an intramuscular injection of 500mg of progesterone (n=387) or served as control (n=396) and did not receive progesterone treatment. Cows were inseminated 12h after being detected in estrus. Pregnancy was diagnosed 40-45 days later by transrectal palpation. Progesterone administration improved (P<0.05) the percentage of cows detected in estrus in multiparous [(192/255) 75% vs (161/267) 60%], but not in primiparous cows [93/132 (70%) vs 90/129 (70%)]. Progesterone treatment increased P/AI in multiparous [53/192 (28%) vs 27/161 (17%)] but not in primiparous cows [25/93 (27%) vs 29/90 (32%)]. The incidence of twin births tended to be lower (P=0.09) in cows treated with progesterone [1/74 (1%)] than in the control group [4/53 (7%)]. It is concluded that progesterone administration during estrus synchronization with two PGF2alpha injections in dairy cows improves estral response and increases P/AI in multiparous, but not in primiparous cows, and tended to decrease the incidence of twin births. PMID- 26833056 TI - Vitamin D deficiency is associated with high prevalence of diabetes in Kuwaiti adults: results from a national survey. AB - BACKGROUND: Vitamin D homeostasis may play a critical role in glucose metabolism. Little is known on vitamin D deficiency and its association with diabetes in countries of the Arabia Gulf where the population is experiencing a rapid increase in the incidence of diabetes. METHODS: In a cross-sectional study of 960 adults enrolled in the first National Nutrition Survey of the State of Kuwait (NNSSK), we examined vitamin D status in association with the prevalence of diabetes and prediabetes. Vitamin D status was measured by serum levels of 25 hydroxyvitami D (25(OH)D). Prevalences of diabetes and prediabetes were determined based on fasting glucose and HbA1C levels. RESULTS: The median level of serum 25(OH)D in Kuwaiti adults was 13.8 ng/ml. Approximately 56 % of the Kuwaiti adults had vitamin D inadequacy (25(OH)D = 12-19.9 ng/ml), and 27 % had vitamin D deficiency (25(OH)D < 12 ng/ml). The prevalences of prediabetes and diabetes were 40 and 27 %, respectively. Vitamin D inadequacy (OR = 1.7, 95 % CI: 1.0-2.9) and deficiency (OR =2.0, 95 % CI: 1.1-3.3) was each associated with about two-fold increased odds of prediabetes compared to sufficient vitamin D status (25(OH)D >= 20 ng/ml). Vitamin D inadequacy (OR =2.1, 95 % CI: 1.2-3.7) and deficiency (OR =2.0, 95 % CI: 1.1-3.9) were also associated with two-fold increased odds of diabetes. CONCLUSIONS: Data from Kuwaiti's first nutrition nutritional survey suggests a very high prevalence of vitamin D deficiency in Kuwaiti adults. Associations of low vitamin D status and high prevalence of diabetes point to the need of continuous monitoring of vitamin D status and further evaluating potential health consequences in this high-risk population. PMID- 26833057 TI - Prognostic role of left atrial strain and its combination index with transmitral E-wave velocity in patients with atrial fibrillation. AB - Left atrial (LA) strain can reflect LA remodeling and is reduced in atrial fibrillation (AF) patients with prior stroke. This study sought to examine the ability of LA strain in predicting subsequent stroke event in AF and also evaluated whether E/LA strain could predict cardiovascular (CV) events in these patients. In 190 persistent AF patients, we performed comprehensive echocardiography with assessment of LA strain. There were 69 CV events including 19 CV death, 32 hospitalizations for heart failure, 3 myocardial infarctions, and 15 strokes during an average follow-up of 29 months. Multivariate analysis showed old age, chronic heart failure, increased left ventricular (LV) mass index, and increased E/LA strain were associated with CV events and decreased LA strain was associated with subsequent stroke event. The addition of E/LA strain and LA strain to a model containing CHA2DS2-VASc score and LV function significantly improved the values in predicting CV events and subsequent stroke event, respectively. In conclusion, E/LA strain and LA strain were respectively useful in predicting CV events and subsequent stroke event in AF. E/LA strain and LA strain could provide incremental values for CV outcome and subsequent stroke outcome prediction over conventional clinical and echocardiographic parameters in AF, respectively. PMID- 26833059 TI - Update on the Use of Ultrasound in Vascular Anomalies. AB - Advances in our understanding of the biology and therapy of vascular anomalies have made this condition a common reason for consulting a dermatologist. In addition, multidisciplinary units have been created to manage patients with complex vascular anomalies. Although most vascular anomalies are diagnosed based on clinical findings, a thorough evaluation often requires additional imaging tests to determine the nature, extension, and prognosis of these lesions. Because it is fast and noninvasive, ultrasound is usually the first imaging test ordered. In the present review, we provide a state-of-the-art synthesis of key concepts in the ultrasound examination of vascular anomalies so that they are more accessible to clinicians and medical imaging specialists involved in the management of these lesions. PMID- 26833060 TI - Primum Non Nocere or How to Create a Culture of Patient Safety. PMID- 26833058 TI - Polydatin ameliorates lipid and glucose metabolism in type 2 diabetes mellitus by downregulating proprotein convertase subtilisin/kexin type 9 (PCSK9). AB - BACKGROUND: Abnormalities in lipid and glucose metabolism are constantly observed in type 2 diabetes. However, these abnormalities can be ameliorated by polydatin. Considering the important role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in metabolic diseases, we explore the possible mechanism of polydatin on lipid and glucose metabolism through its effects on PCSK9. METHODS: An insulin resistant HepG2 cell model induced by palmitic acid (PA) and a db/db mice model were used to clarify the role of polydatin on lipid and glucose metabolism. RESULTS: In insulin-resistant HepG2 cells, polydatin upregulated the protein levels of LDLR and GCK but repressed PCSK9 protein expression, besides, polydatin also inhibited the combination between PCSK9 and LDLR. Knockdown and overexpression experiments indicated that polydatin regulated LDLR and GCK expressions through PCSK9. In the db/db mice model, we found that polydatin markedly enhanced GCK and LDLR protein levels, and inhibited PCSK9 expression in the liver. Molecular docking assay was further performed to analyze the possible binding mode between polydatin and the PCSK9 crystal structure (PDB code: 2p4e), which indicated that steady hydrogen bonds formed between polydatin and PCSK9. CONCLUSIONS: Our study indicates that polydatin ameliorates lipid and glucose metabolism in type 2 diabetes mellitus by downregulating PCSK9. PMID- 26833061 TI - Unusual Ultrasound Appearance of Subungual Keratoacanthoma With Clinical and Histological Correlation. PMID- 26833062 TI - Follicular Lichen Planus Caused by Wig Use: An Unusual Case of Koebner Phenomenon. PMID- 26833064 TI - The Disappearance of Sudden Infant Death Syndrome: Has the Clock Turned Back? PMID- 26833063 TI - Identification and characterization of abundant repetitive sequences in Eragrostis tef cv. Enatite genome. AB - BACKGROUND: Eragrostis tef is an allotetraploid (2n = 4 * = 40) annual, C4 grass with an estimated nuclear genome size of 730 Mbp. It is widely grown in Ethiopia, where it provides basic nutrition for more than half of the population. Although a draft assembly of the E. tef genome was made available in 2014, characterization of the repetitive portion of the E. tef genome has not been a subject of a detailed analysis. Repetitive sequences constitute most of the DNA in eukaryotic genomes. Transposable elements are usually the most abundant repetitive component in plant genomes. They contribute to genome size variation, cause mutations, can result in chromosomal rearrangements, and influence gene regulation. An extensive and in depth characterization of the repetitive component is essential in understanding the evolution and function of the genome. RESULTS: Using new paired-end sequence data and a de novo repeat identification strategy, we identified the most repetitive elements in the E. tef genome. Putative repeat sequences were annotated based on similarity to known repeat groups in other grasses. Altogether we identified 1,389 medium/highly repetitive sequences that collectively represent about 27% of the teff genome. Phylogenetic analyses of the most important classes of TEs were carried out in a comparative framework including paralog elements from rice and maize. Finally, an abundant tandem repeat accounting for more than 4% of the whole genome was identified and partially characterized. CONCLUSIONS: Analyzing a large sample of randomly sheared reads we obtained a library of the repetitive sequences of E. tef. The approach we used was designed to avoid underestimation of repeat contribution; such underestimation is characteristic of whole genome assembly projects. The data collected represent a valuable resource for further analysis of the genome of this important orphan crop. PMID- 26833065 TI - Head and neck paragangliomas: diffusion weighted and dynamic contrast enhanced magnetic resonance imaging characteristics. AB - BACKGROUND: To determine the feature values of head and neck paragangliomas on diffusion-weighted imaging (DWI) and dynamic contrast enhanced (DCE) magnetic resonance imaging (MRI). METHODS: Patients with primary head and neck paraganglioma who underwent both DWI and DCE-MRI before treatment between January 2010 and June 2013 were identified. Two radiologists assessed apparent diffusion coefficient (ADC) values on DWI and kinetic characteristics on DCE-MRI. The time intensity curves (TICs) and dynamic parameters, including peak height (PH), maximum enhancement ratio (ER(max)), time to peak enhancement (T(peak)) and maximum rise slope (Slope(max)), were generated and evaluated. RESULTS: Ten patients with head and neck paraganglioma were retrospectively analyzed. On conventional MRI, the tumors demonstrated as well-circumscribed, strongly enhanced lesions. Mean ADC value of the lesions was 1.12 +/- 0.15 * 10(-3) mm(2)/s. The TICs demonstrated washout pattern (type-III) in all lesions. The mean PH, ER(max), T(peak) and Slope(max) value was 121.24 +/- 63.99, 193.79 +/- 67.18, 8.16 +/- 3.29 and 25.42 +/- 7.91, respectively. CONCLUSIONS: Head and neck paragangliomas demonstrate distinctive DWI and DCE-MRI results than for other benign tumors which should be taken into account in further evaluation of MRI on head and neck lesions. PMID- 26833067 TI - Variability in Multisensory Responses Predicts the Self-Space. AB - Our brains distinguish between stimuli that are close enough to interact with our bodies and those that are further away by generating a multisensory representation of space near the self, termed peripersonal space. Recent findings show that variability in neuronal response to audio-tactile stimuli predicts the location of the peripersonal space boundary at the individual level. PMID- 26833066 TI - Neural responses to a modified Stroop paradigm in patients with complex chronic musculoskeletal pain compared to matched controls: an experimental functional magnetic resonance imaging study. AB - BACKGROUND: Chronic musculoskeletal pain (CMSKP) is attentionally demanding, complex and multi-factorial; neuroimaging research in the population seen in pain clinics is sparse. A better understanding of the neural activity underlying attentional processes to pain related information compared to healthy controls may help inform diagnosis and management in the future. METHODS: Blood oxygenation level dependent functional magnetic resonance imaging (BOLD fMRI) compared brain responses in patients with CMSKP (n = 15) and healthy controls (n = 14) while completing a modified Stroop task using pain-related, positive emotional, and neutral control words. RESULTS: Response times in the Stroop task were no different for CMSKP patients compared with controls, but patients were less accurate in their responses to all word types. BOLD fMRI responses during presentation of pain-related words suggested increases in neural activation in patients compared to controls in regions previously reported as being involved in pain perception and emotion: the anterior cingulate cortex, insula and primary and secondary somatosensory cortex. No fMRI differences were seen between groups in response to positive or control words. CONCLUSIONS: Using this modified Stroop tasks, specific differences were identified in brain activity between CMSKP patients and controls in response to pain-related information using fMRI. This provided evidence of differences in the way that pain-related information is processed in those with chronic complex musculoskeletal pain that were not detectable using the behavioural measures of speed and accuracy. The study may be helpful in gaining new insights into the impact of attention in those living with chronic pain. PMID- 26833068 TI - Perioperative risk factors in patients with a femoral neck fracture - influence of 25-hydroxyvitamin D and C-reactive protein on postoperative medical complications and 1-year mortality. AB - BACKGROUND: This study examined the association of 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP) with postoperative medical complications and one year mortality of elderly patients sustaining a low-energy cervical hip fracture scheduled for surgery. We hypothesized that vitamin D deficiency and CRP in these patients might be associated with an increased 1-year mortality. METHODS: The prospective single-center cohort study included 209 patients with a low-energy medial femoral neck fracture; 164 women aged over 50 years and 45 men aged over 60 years. Referring to 1-year mortality and postoperative medical complications multiple logistic regression analysis including 10 co-variables (age, sex, BMI, ASA, creatinine, CRP, leukocytes hemoglobin, 25(OH)D, vitamin D supplementation at follow-up) was performed. RESULTS: Vitamin D deficiency was prevalent in 87 % of all patients. In patients with severe (<10 ng/ml) and moderate (10-20 ng/ml) vitamin D deficiency one year mortality was 29 % and 13 %, respectively, compared to 9 % in patients with > 20 ng/ml 25(OH)D levels (p =0.027). Patients with a mild (CRP 10-39.9 mg/l) or active inflammatory response (CRP >= 40 mg/l) showed a higher one year mortality of 33 % and 40 % compared to 16 % in patients with no (CRP < 10 mg/l) inflammatory response (p = 0.002). Multiple logistic regression analysis identified CRP (OR 1.01, 95 % CI 1.00-1.02; p = 0.007), but not 25(OH)D (OR 0.97, 95 % CI 0.89-1.05; p = 0.425) as an independent predictor for one year mortality. 20 % of patients suffered in-hospital postoperative medical complications (i.e. pneumonia, thromboembolic events, etc.). 25(OH)D (OR 0.89, 95 % CI 0.81-0.97; p = 0.010), but not CRP (OR 1.01, 95 % CI 1.00-1.02; p = 0.139), was identified as an independent risk factor. CONCLUSION: In elderly patients with low-energy cervical hip fracture, 25(OH)D is independently associated with postoperative medical complications and CRP is an independent predictor of one year mortality. PMID- 26833069 TI - US-localized diffuse optical tomography in breast cancer: comparison with pharmacokinetic parameters of DCE-MRI and with pathologic biomarkers. AB - BACKGROUND: To correlate parameters of Ultrasonography-guided Diffuse optical tomography (US-DOT) with pharmacokinetic features of Dynamic contrast-enhanced (DCE)-MRI and pathologic markers of breast cancer. METHODS: Our institutional review board approved this retrospective study and waived the requirement for informed consent. Thirty seven breast cancer patients received US-DOT and DCE-MRI with less than two weeks in between imaging sessions. The maximal total hemoglobin concentration (THC) measured by US-DOT was correlated with DCE-MRI pharmacokinetic parameters, which included K(trans), k ep and signal enhancement ratio (SER). These imaging parameters were also correlated with the pathologic biomarkers of breast cancer. RESULTS: The parameters THC and SER showed marginal positive correlation (r = 0.303, p = 0.058). Tumors with high histological grade, negative ER, and higher Ki-67 expression >= 20% showed statistically higher THC values compared to their counterparts (p = 0.019, 0.041, and 0.023 respectively). Triple-negative (TN) breast cancers showed statistically higher K(trans) values than non-TN cancers (p = 0.048). CONCLUSION: THC obtained from US-DOT and K(trans) obtained from DCE-MRI were associated with biomarkers indicative of a higher aggressiveness in breast cancer. Although US-DOT and DCE-MRI both measured the vascular properties of breast cancer, parameters from the two imaging modalities showed a weak association presumably due to their different contrast mechanisms and depth sensitivities. PMID- 26833070 TI - Retention of health workers in rural Sierra Leone: findings from life histories. AB - BACKGROUND: Sierra Leone has faced a shortage and maldistribution of staff in its post-conflict period. This long-standing challenge is now exacerbated by the systemic shock and damage wrought by Ebola. This study aimed to investigate the importance of different motivation factors in rural areas in Sierra Leone and thus to contribute to better decisions on financial and non-financial incentive packages, here and in similar contexts. METHODS: This article is based on participatory life histories, conducted in 2013 with 23 health workers (doctors, nurses, midwives and Community Health Officers) in four regions of Sierra Leone who had worked in the sector since 2000. Although the interviews covered a wide range of themes, here we present findings on motivating and demotivating factors for staff, especially those in rural areas, based on thematic analysis of transcripts. RESULTS: Rural health workers face particular challenges, some of which stem from the difficult terrain, which add to common disadvantages of rural living (poor social amenities, etc.). Poor working conditions, emotional and financial costs of separation from families, limited access to training, longer working hours (due to staff shortages) and the inability to earn from other sources make working in rural areas less attractive. Moreover, rules on rotation which should protect staff from being left too long in rural areas are not reported to be respected. By contrast, poor management had more resonance in urban areas, with reports of poor delegation, favouritism and a lack of autonomy for staff. Tensions within the team over unclear roles and absenteeism are also significant demotivating factors in general. CONCLUSIONS: This study provides important policy-focused insights into motivation of health workers and can contribute towards building a resilient and responsive health system, incorporating the priorities and needs of health workers. Their voices and experiences should be taken into account as the post-Ebola landscape is shaped. PMID- 26833071 TI - In vitro antibacterial activity and in vivo efficacy of hydrated clays on Mycobacterium ulcerans growth. AB - BACKGROUND: Buruli ulcer, caused by Mycobacterium ulcerans, is a localized skin lesion that can progress to extensive ulceration and necrosis if left untreated. Unpublished studies of hydrated clays for therapeutic, topical treatment of Buruli ulcer suggest that specific clay mineral products may have beneficial effects on wound healing. In this study, we evaluated the in vitro antibacterial activity of a panel of clay mixtures and their derivative leachates against M. ulcerans and assessed the in vivo efficacy of topically-applied, hydrated clays on Buruli ulcer progression in mice infected with M. ulcerans. METHODS: M. ulcerans 1615 was incubated with 10% suspensions of CB07, CB08, CB09, CB10, and BY07 clay mixtures, and survival was determined over 28 days. For animal experiments, we examined the effect of topical hydrated clay therapy on Buruli ulcer progression in vivo in mouse tails subcutaneously infected with M. ulcerans 1615. RESULTS: The CB07, CB08, and CB09 clays exhibited bactericidal activity against M. ulcerans after 7, 14, 21, and 28 days of incubation. In contrast, clay leachates exhibited inhibitory, bacteriostatic effects on M. ulcerans growth in vitro. After establishing an ulcerative M. ulcerans infection for three months, ulcerated regions of the tails were treated once daily (five consecutive days per week) for 22 days with hydrated CB09 clay poultices. Mice in the clay treatment group exhibited healing as assessed by gross morphological changes and a reduction in M. ulcerans present in the wounds. CONCLUSIONS: These data reveal that specific clays exhibit in vitro bactericidal activity against M. ulcerans and that hydrated clay poultices may offer a complementary and integrative strategy for topically treating Buruli ulcer disease. PMID- 26833072 TI - Synthesis and Evaluation of Phenyliminoindolin-Containing Phenylacetamide Derivatives with the Antidepressant and Anticonvulsant Effects. AB - BACKGROUND: To discover a novel antidepressant-like effect and anticonvulsant compound, seventeen new 2-oxo-3-phenyliminoindolin-1-Nphenylacetamide compounds were synthesized and screened for the antidepressant activity and anticonvulsant effects. METHOD: 2-oxo-3-phenyliminoindolin-1-N-phenylacetamide derivatives were synthesized with indoline-2, 3-dione as the starting material, through a nucleophilic substitution reaction and a nucleophilic addition-elimination reaction. The target derivatives 2a-2q were evaluated the antidepressant-like activity using the FST, TST, and evaluated anticonvulsant effect by MES test. The main monoamine neurotransmitters and their metabolites in mouse brain regions were also simultaneously determined by HPLC-ECD. RESULTS: It was observed that 13 compounds showed significant reductions in the immobility time in the FST at a concentration of 50 mg/kg. Compound 2b was found to have the most potent antidepressant activity in the FST and the TST for 30 min after treatment. Compound 2b significantly increased the concentrations of the main neurotransmitters 5-HT, NE and the metabolite (5-HIAA, suggesting that the effects of compound 2b may be mediated through these neurotransmitters. As assessed using maximal electroshock, 13 compounds showed the anticonvulsant effects administered at the concentration levels of 100 or 300 mg/kg. Compound 2b showed anticonvulsant effect. Compound 2b could potentially be used as adjuncts of the antidepressants to treat depression in patients with epilepsy. CONCLUSION: In conclusion, compound 2b produced significant antidepressant-like activity and the mechanism of action may be due to increased 5-HT and NE in the mouse. Compound 2b showed more anticonvulsant effect. Compound 2b could potentially be used as adjuncts of the antidepressants to treat depression in patients with epilepsy. PMID- 26833073 TI - Synthesis, Antibacterial Activity, Interaction with Nucleobase and Molecular Docking Studies of 4-Formylbenzoic Acid Based Thiazoles. AB - BACKGROUND: Synthesis, characterization and investigation of antibacterial activity of ten novel Schiff base derivatives of 4-formylbenzoic acid is presented. Their structures were determined using 1H and 13CNMR, EI(+)-MS and elemental analyses. Additionally, DFT calculations of interaction energies in complexes of the novel drugs and DNA bases are carried out. OBJECTIVE: Design and synthesis of thiazole derivatives with benzoic acid scaffold to obtain compounds with an improved antibacterial activity. METHOD: The examined compounds were screened in vitro for antibacterial activity using the broth microdilution method. Geometrical parameters of the investigated complexes were optimized within the Density Functional Theory (DFT) approximation using the B3LYP functional and the 6-311G** basis set. The docking simulations were performed using the FlexX docking module. RESULTS: Among the derivatives, compound 4b showed very strong bacterial activity against staphylococci, MIC 1.95-3.91 ug/ml, micrococci, MIC 0.98 ug/ml, and Bacillus spp., MIC 7.81-15.62 ug/ml. The compounds 4c, 4d, 4e and 4j also showed high bioactivity against staphylococci, MIC 3.91-31.25 ug/ml, and micrococci, MIC 0.98-15.62 ug/ml. Interaction energy values for investigated guanine complexes are about 2 kcal/mol lower than for the corresponding cytosine complexes. Molecular docking studies of all compounds on the active sites of bacterial enzymes indicated gyrase B as possible target. CONCLUSION: To conclude, an efficient and economic method for the synthesis of thiazoles containing benzoic acid moiety has been developed. The results of antibacterial screenings reveal that some obtained compounds show high to very strong antibacterial activity. The DFT calculations showed that interaction of the obtained drugs with guanine is stronger than with cytosine. Molecular docking studies of all compounds on the active sites of bacterial enzymes indicated gyrase B as possible target. PMID- 26833074 TI - Ether and Carbamate Derivatives of 3-quinuclidinol and 3- hydroxymethylquinuclidine: Synthesis and Evaluation as Nicotinic Ligands. AB - BACKGROUND: A lead quinuclidine-based nicotinic ligand (EQA) served as the basis for the design of novel compounds. A new series of 3-substituted quinuclidines was designed, synthesized and evaluated as nicotinic ligands. METHODS: The goal was to improve affinity for nicotinic receptors in the CNS. Interatomic distance calculations were performed on the proposed compounds as well as, known nicotinic ligands. The proposed compounds were then synthesized, characterized and evaluated in in vitro assays as nicotinic receptor ligands. RESULTS: Compounds 9a and 9b were found to inhibit the specific binding of 3H-(S)-Nicotine with Ki values of 48 nM and 42 nM respectively, indicating high affinity interactions with the alpha4beta2 subtype. Data suggest that several compounds act as partial agonists at CNS receptors with an efficacy between 28 and 40% and are potent partial activators of human muscle type receptors (alpha1beta1gammadelta Emax= 80% that of 100 uM nicotine). CONCLUSIONS: Together these results indicate a partial agonism at muscle type receptors (ca. 40%) with no significant activation of rat ganglion-type receptors (alpha3beta4*: asterisk indicates potential additional subunit that could partner to form the ganglionic receptor). The partial agonism inducing dopamine release from striatal synaptosomes (alpha4beta2alpha6alpha4beta2beta3, and/or alpha6beta2beta3) suggest that these compounds may in addition be acting at the alpha4beta2 and/or the alpha6beta3* receptors. The partial agonists reported herein are interesting nicotinic ligands worthy of further investigation. PMID- 26833076 TI - Synthesis and Biological Evaluation of Novel 1,3,4-thiadiazole Derivatives Incorporating Benzisoselenazolone Scaffold as Potential Antitumor Agents. AB - BACKGROUND: Based on the biological significance of benzisoselenazolone and 1,3,4 thiadiazole, a series of novel 1,3,4-thiadiazole derivatives incorporating benzisoselenazolone scaffold were designed and synthesized with ebselen as a lead compound. METHODS: Meanwhile, their in vitro antitumor activities were evaluated against SMMC-7721, MCF-7 and A549 human cancer cell lines by CCK-8 assay. RESULTS: The preliminary bioassay results demonstrated that all tested compounds 4a-q showed potent antitumor activities, and some compounds exhibited better effects than positive control ethaselen and 5-fluorouracil (5-FU) against various cancer cell lines. Furthermore, compounds 4b and 4m showed significant antitumor activities against SMMC-7721 cells with IC50 values of 1.89 and 1.89 MUM, respectively. Compounds 4c and 4n displayed highly effective biological activities against MCF-7 cells with IC50 values of 2.88 and 2.28 MUM, respectively. Compound 4i showed the best inhibitory effect against A549 cells with IC50 value of 1.76 MUM. CONCLUSION: The pharmacological results suggest that the substituent groups of phenyl ring on the 1,3,4-thiadiazole are vital for modulating antitumor activities against various cancer cell lines. PMID- 26833075 TI - In-Vitro Anticancer Evaluation and Docking Study of Novel Benzo[g] Quinazoline sulfonamide Derivatives. AB - BACKGROUND: Quinazoline and sulfonamide derivatives are considered to be important classes of drugs due to their wide range of biological activities especially anticancer. METHODS: A novel series of sulfonamides incorporating benzo[g] quinazolinemoieties 2-19 and sulfonyl containing benzo[g] quinazolinemoieties 20, 21 were designed and synthesized starting from 4- chlorobenzo[g] quinazoline 1. In-vitro screening as anticancer agents was done for the synthesized compounds. Molecular docking study was also performed to explore the binding interactions of the synthesized compounds within the active site of carbonic anhydrase IX (CA IX), which most commonly expressed in some types of cancer cells. CONCLUSION: The results indicated that the most potent compounds were 2 and 7 showing effectiveness on more than one cell line. PMID- 26833077 TI - Efficient Synthesis and Discovery of Schiff Bases as Potent Cholinesterase Inhibitors. AB - BACKGROUND: The search for new cholinesterase inhibitors is still a promising approach for management of Alzheimer's disease. Schiff bases are considered as important class of organic compounds, which have wide range of applications including as enzyme inhibitors. In the present study, a new green ionic liquid mediated strategy was developed for convenient synthesis of two series of Schiff bases 3(a-j) and 5(a-j) as potential cholinesterase inhibitors using aromatic aldehydes and primary amines in [bmim]Br. METHODS: The synthesized compounds were evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potential by modified Ellman's method. The molecular interactions between the most active compound and the enzyme were analyzed by molecular docking. RESULTS: Among them, 3j displayed higher inhibitory activities than reference drug, galanthamine, with IC50 values of 2.05 and 5.77 uM, for AChE and BChE, respectively. Interestingly, all the compounds except 3b displayed higher BChE inhibitions than galanthamine with IC50 values ranging from 5.77 to 18.52 uM. Molecular docking of compound 3j inside the TcAChE and hBChE completely coincided with the inhibitory activities observed. The compound forms strong hydrogen bonding at the peripheral anionic site of AChE whereas on BChE, it had hydrophobic and mild polar interactions. CONCLUSION: An efficient and eco friendly synthetic methodology has been developed to synthesize Schiff bases in a very short reaction time and excellent yields in ionic solvent, whereby the compounds from series 3 showed promising cholinesterase inhibitory activity. PMID- 26833078 TI - Voxelized Model of Brain Infusion That Accounts for Small Feature Fissures: Comparison With Magnetic Resonance Tracer Studies. AB - Convection enhanced delivery (CED) is a promising novel technology to treat neural diseases, as it can transport macromolecular therapeutic agents greater distances through tissue by direct infusion. To minimize off-target delivery, our group has developed 3D computational transport models to predict infusion flow fields and tracer distributions based on magnetic resonance (MR) diffusion tensor imaging data sets. To improve the accuracy of our voxelized models, generalized anisotropy (GA), a scalar measure of a higher order diffusion tensor obtained from high angular resolution diffusion imaging (HARDI) was used to improve tissue segmentation within complex tissue regions of the hippocampus by capturing small feature fissures. Simulations were conducted to reveal the effect of these fissures and cerebrospinal fluid (CSF) boundaries on CED tracer diversion and mistargeting. Sensitivity analysis was also conducted to determine the effect of dorsal and ventral hippocampal infusion sites and tissue transport properties on drug delivery. Predicted CED tissue concentrations from this model are then compared with experimentally measured MR concentration profiles. This allowed for more quantitative comparison between model predictions and MR measurement. Simulations were able to capture infusate diversion into fissures and other CSF spaces which is a major source of CED mistargeting. Such knowledge is important for proper surgical planning. PMID- 26833079 TI - The study of the transformer gene from Bactrocera dorsalis and B. correcta with putative core promoter regions. AB - BACKGROUND: The transformer (tra) is a sex determining switch in different orders of insects, including Diptera, as in the family Tephritidae. The lifelong autoregulatory loop of tra female-specific splicing can be reset by the intervention of male-specific primary signals (M factor). In early development, the functional female and truncated male TRA proteins relay the sexual fates to the alternative splicing of a bisexual switch gene, doublesex (dsx) cascading the sexual differentiation processes. Bactrocera dorsalis (Hendel) and Bactrocera correcta (Bezzi) are among the Bactrocera model worldwide key pests. Area-wide integrated pest management using the male-only Sterile Insect Technique (SIT) relying on genetic sexing systems is effective in control programs. We undertook the molecular characterization and comparative studies of the tra orthologues in the Bactrocera species, including the Salaya1 genetic sexing strain (GSS). RESULTS: RT-PCR revealed that B. dorsalis tra (Bdtra) and B. correcta tra (Bctra) transcripts contained conservation of both constitutive exons and male-specific exons as in other Bactrocera. However, new Bdtra male-specific exons were retained, diversifying the pattern of the male-specifically spliced transcripts. The coding sequences of tra were highly conserved in Bactrocera (86-95%) but less so among related genera (61-65%) within the same Tephritidae family. A conservation of deduced amino acid sequences (18 residues), called the TEP region, was identified to be distinctive among tephritids. The 5' regulatory sequence containing many structural characteristics of the putative core promoter was discovered in B. correcta. The expression patterns of Bdtra and Bctra were sex-specifically spliced and the signals relayed to the dsx genes in the adult wild-types. However, the coexistence of male- and female-specifically spliced transcripts (980 and 626 bp, respectively) of the B. dorsalis wild-type strain was found in the Salaya1 GSS adult males. The Bdtra RNA interference masculinized the XX karyotype females into pseudomales, but their testes were mostly not well developed. CONCLUSIONS: Bdtra and Bctra have sex-specific splicing, similar to Bactroceras, Ceratitis capitata (Wiedemann), and Anastrephas. A newly identified TEP region is proposed in tephritids. A putative core promoter has been discovered in Bctra. PMID- 26833080 TI - Perspectives on the design and methodology of periconceptional nutrient supplementation trials. AB - Periconceptional supplementation could extend the period over which maternal and fetal nutrition is improved, but there are many challenges facing early-life intervention studies. Periconceptional trials differ from pregnancy supplementation trials, not only because of the very early or pre-gestational timing of nutrient exposure but also because they generate subsidiary information on participants who remain non-pregnant. The methodological challenges are more complex although, if well designed, they provide opportunities to evaluate concurrent hypotheses related to the health of non-pregnant women, especially nulliparous adolescents. This review examines the framework of published and ongoing randomised trial designs. Four cohorts typically arise from the periconceptional trial design--two of which are non-pregnant and two are pregnant -and this structure provides assessment options related to pre-pregnant, maternal, pregnancy and fetal outcomes. Conceptually the initial decision for single or micronutrient intervention is central--as is the choice of dosage and content--in order to establish a comparative framework across trials, improve standardisation, and facilitate interpretation of mechanistic hypotheses. Other trial features considered in the review include: measurement options for baseline and outcome assessments; adherence to long-term supplementation; sample size considerations in relation to duration of nutrient supplementation; cohort size for non-pregnant and pregnant cohorts as the latter is influenced by parity selection; integrating qualitative studies and data management issues. Emphasis is given to low resource settings where high infection rates and the possibility of nutrient-infection interactions may require appropriate safety monitoring. The focus is on pragmatic issues that may help investigators planning a periconceptional trial. PMID- 26833082 TI - Molecular Correlates of Circadian Clocks in Fruit Fly Drosophila melanogaster Populations Exhibiting early and late Emergence Chronotypes. AB - Although association of circadian clock properties with the timing of rhythmic behaviors (chronotype) has been extensively documented over several decades, recent studies on mice and Drosophila have failed to observe such associations. In addition, studies on human populations that examined effects of clock gene mutations/polymorphisms on chronotypes have revealed disparate and often contradictory results, thereby highlighting the need for a suitable model organism to study circadian clocks' role in chronotype regulation, the lack of which has hindered exploration of the underlying molecular-genetic bases. We used a laboratory selection approach to raise populations of Drosophila melanogaster that emerge in the morning (early) or in the evening (late), and over 14 years of continued selection, we report clear divergence of their circadian phenotypes. We also assessed the molecular correlates of early and late emergence chronotypes and report significant divergence in transcriptional regulation, including the mean phase, amplitude and levels of period (per), timeless (tim), clock (clk) and vrille (vri) messenger RNA (mRNA) expression. Corroborating some of the previously reported light-sensitivity and oscillator network coupling differences between the early and the late populations, we also report differences in mRNA expression of the circadian photoreceptor cryptochrome (cry) and in the mean phase, amplitude and levels of the neuropeptide pigment-dispersing factor (PDF). These results provide the first-ever direct evidence for divergent evolution of molecular circadian clocks in response to selection imposed on an overt rhythmic behavior and highlight early and late populations as potential models for chronotype studies by providing a preliminary groundwork for further exploration of molecular-genetic correlates underlying circadian clock-chronotype association. PMID- 26833081 TI - Circadian Modulation of Alcohol-Induced Sedation and Recovery in Male and Female Drosophila. AB - Delineating the factors that affect behavioral and neurological responses to alcohol is critical to facilitate measures for preventing or treating alcohol abuse. The high degree of conserved molecular and physiological processes makes Drosophila melanogaster a valuable model for investigating circadian interactions with alcohol-induced behaviors and examining sex-specific differences in alcohol sensitivity. We found that wild-type Drosophila exhibited rhythms in alcohol induced sedation under light-dark and constant dark conditions with considerably greater alcohol exposure necessary to induce sedation during the late (subjective) day and peak sensitivity to alcohol occurring during the late (subjective) night. The circadian clock also modulated the recovery from alcohol induced sedation with flies regaining motor control significantly faster during the late (subjective) day. As predicted, the circadian rhythms in sedation and recovery were absent in flies with a mutation in the circadian gene period or arrhythmic flies housed in constant light conditions. Flies lacking a functional circadian clock were more sensitive to the effects of alcohol with significantly longer recovery times. Similar to other animals and humans, Drosophila exhibit sex-specific differences in alcohol sensitivity. We investigated whether the circadian clock modulated the rhythms in the loss-of-righting reflex, alcohol induced sedation, and recovery differently in males and females. We found that both sexes demonstrated circadian rhythms in the loss-of-righting reflex and sedation with the differences in alcohol sensitivity between males and females most pronounced during the late subjective day. Recovery of motor reflexes following alcohol sedation also exhibited circadian modulation in male and female flies, although the circadian clock did not modulate the difference in recovery times between the sexes. These studies provide a framework outlining how the circadian clock modulates alcohol-induced behaviors in Drosophila and identifies sexual dimorphisms in the circadian modulation of alcohol behaviors. PMID- 26833083 TI - Direct and Indirect Costs of Chronic and Episodic Migraine in the United States: A Web-Based Survey. AB - OBJECTIVE: The objective of this study was to compare the societal direct and indirect costs of chronic and episodic migraine in the United States. BACKGROUND: Episodic and chronic migraine are distinguished by the frequency of headache days. Chronic migraine has a greater overall impact on quality of life than does episodic migraine. Individuals with chronic migraine also use more healthcare resources (resulting in higher direct costs) and experience greater decreases in productivity (resulting in higher indirect costs) than those with episodic migraine as shown in the American Migraine Prevalence and Prevention (AMPP) Study. METHODS: The International Burden of Migraine Study utilized a web-based questionnaire to elicit data on several topics related to the burden of migraine illness, including health resource utilization and productivity losses. Potential survey participants were identified by Synovate Healthcare (Chicago, IL, USA) from a pool of registered panelists from various countries. The panelists were screened online to determine eligibility and to identify individuals with migraine (episodic or chronic), based on reported symptoms. Participants from the United States were divided into episodic and chronic migraine groups, based on reported headache-day per month frequency. Direct and indirect costs were estimated by applying estimated unit costs to reported headache-related productivity losses and resource use. Costs were compared between participants with episodic and chronic migraine. RESULTS: Mean [standard deviation] total annual cost of headache among people with chronic migraine ($8243 [$10,646]) was over three times that of episodic migraine ($2649 [$4634], P < .001). Participants with chronic migraine had significantly greater direct medical costs ($4943 [$6382]) and indirect (lost productivity) costs ($3300 [$6907]) than did participants with episodic migraine (direct, $1705 [$3591]; indirect, $943 [$2084]) (P < .001 for each). Unlike previous findings, direct medical costs constituted the majority of total headache-related costs for both chronic migraine (60.0%, $4943 of $8243) and episodic migraine (64.3%, $1705 of $2649) participants. A large portion of direct medical costs are attributable to pharmaceutical utilization among both chronic migraine (80%, $3925 of 4943) and episodic migraine (70%, $1196 of $1705) participants. CONCLUSION: The results of this study build on previous results of the AMPP Study, demonstrating that headache-related direct, indirect, and total costs are significantly greater among individuals with chronic migraine than with episodic migraine in the United States. PMID- 26833084 TI - QM/MM study on the enantioselectivity of spiroacetalization catalysed by an imidodiphosphoric acid catalyst: how confinement works. AB - The mechanism for the spiroacetalization of enol-ethers 1 and 2 promoted by chiral phosphoric acid (CPA) catalyst (I) and by chiral imidodiphosphoric acid catalyst (II) has been investigated by QM/MM methods. The computed levels of enantioselectivity following exhaustive conformational analysis is in close agreement with the sense and magnitude of experimental results. Small substrates fit inside catalyst I to yield both enantiomers, in agreement with the absence of asymmetric induction for this reaction, while for catalyst II chiral discrimination between TS structures is possible. Unlike reactions catalysed by CPA or CPA derivatives in which steric effects and substrate distortion controls enantioselectivity, we show that chiral discrimination results from the restricted area and direction of possible hydrogen-bonding interactions with a more confined catalyst structure. PMID- 26833085 TI - Joint mouse-human phenome-wide association to test gene function and disease risk. AB - Phenome-wide association is a novel reverse genetic strategy to analyze genome-to phenome relations in human clinical cohorts. Here we test this approach using a large murine population segregating for ~5 million sequence variants, and we compare our results to those extracted from a matched analysis of gene variants in a large human cohort. For the mouse cohort, we amassed a deep and broad open access phenome consisting of ~4,500 metabolic, physiological, pharmacological and behavioural traits, and more than 90 independent expression quantitative trait locus (QTL), transcriptome, proteome, metagenome and metabolome data sets--by far the largest coherent phenome for any experimental cohort (www.genenetwork.org). We tested downstream effects of subsets of variants and discovered several novel associations, including a missense mutation in fumarate hydratase that controls variation in the mitochondrial unfolded protein response in both mouse and Caenorhabditis elegans, and missense mutations in Col6a5 that underlies variation in bone mineral density in both mouse and human. PMID- 26833087 TI - Antisense Transcripts Delimit Exonucleolytic Activity of the Mitochondrial 3' Processome to Generate Guide RNAs. AB - Small, noncoding RNA biogenesis typically involves cleavage of structured precursor by RNase III-like endonucleases. However, guide RNAs (gRNAs) that direct U-insertion/deletion mRNA editing in mitochondria of trypanosomes maintain 5' triphosphate characteristic of the transcription initiation and possess a U tail indicative of 3' processing and uridylation. Here, we identified a protein complex composed of RET1 TUTase, DSS1 3'-5' exonuclease, and three additional subunits. This complex, termed mitochondrial 3' processome (MPsome), is responsible for primary uridylation of ~800 nt gRNA precursors, their processive degradation to a mature size of 40-60 nt, and secondary U-tail addition. Both strands of the gRNA gene are transcribed into sense and antisense precursors of similar lengths. Head-to-head hybridization of these transcripts blocks symmetrical 3'-5' degradation at a fixed distance from the double-stranded region. Together, our findings suggest a model in which gRNA is derived from the 5' extremity of a primary molecule by uridylation-induced, antisense transcription-controlled 3'-5' exonucleolytic degradation. PMID- 26833088 TI - Analysis of Chromatin ADP-Ribosylation at the Genome-wide Level and at Specific Loci by ADPr-ChAP. AB - Chromatin ADP-ribosylation regulates important cellular processes. However, the exact location and magnitude of chromatin ADP-ribosylation are largely unknown. A robust and versatile method for assessing chromatin ADP-ribosylation is therefore crucial for further understanding its function. Here, we present a chromatin affinity precipitation method based on the high specificity and avidity of two well-characterized ADP-ribose binding domains to map chromatin ADP-ribosylation at the genome-wide scale and at specific loci. Our ADPr-ChAP method revealed that in cells exposed to oxidative stress, ADP-ribosylation of chromatin scales with histone density, with highest levels at heterochromatic sites and depletion at active promoters. Furthermore, in growth factor-induced adipocyte differentiation, increased chromatin ADP-ribosylation was observed at PPARgamma target genes, whose expression is ADP-ribosylation dependent. In combination with deep-sequencing and conventional chromatin immunoprecipitation, the established ADPr-ChAP provides a valuable resource for the bioinformatic comparison of ADP ribosylation with other chromatin modifications and for addressing its role in other biologically important processes. PMID- 26833086 TI - Regulated Formation of lncRNA-DNA Hybrids Enables Faster Transcriptional Induction and Environmental Adaptation. AB - Long non-coding (lnc)RNAs, once thought to merely represent noise from imprecise transcription initiation, have now emerged as major regulatory entities in all eukaryotes. In contrast to the rapidly expanding identification of individual lncRNAs, mechanistic characterization has lagged behind. Here we provide evidence that the GAL lncRNAs in the budding yeast S. cerevisiae promote transcriptional induction in trans by formation of lncRNA-DNA hybrids or R-loops. The evolutionarily conserved RNA helicase Dbp2 regulates formation of these R-loops as genomic deletion or nuclear depletion results in accumulation of these structures across the GAL cluster gene promoters and coding regions. Enhanced transcriptional induction is manifested by lncRNA-dependent displacement of the Cyc8 co-repressor and subsequent gene looping, suggesting that these lncRNAs promote induction by altering chromatin architecture. Moreover, the GAL lncRNAs confer a competitive fitness advantage to yeast cells because expression of these non-coding molecules correlates with faster adaptation in response to an environmental switch. PMID- 26833089 TI - Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments. AB - Detailed genomic contact maps have revealed that chromosomes are structurally organized in megabase-sized topologically associated domains (TADs) that encompass smaller subTADs. These domains segregate in the nuclear space to form active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1, or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear subcompartments with distinct chromatin signatures. Focal protein recruitment caused the entire subTAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was found uncoupled from transcription changes, and the enzymatic modification of histones per se was insufficient for repositioning. Collectively, this suggests that trans-associated factors influence three-dimensional compartmentalization independent of their cis effect on local chromatin composition and activity. PMID- 26833090 TI - Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability. AB - XPG is a structure-specific endonuclease required for nucleotide excision repair, and incision-defective XPG mutations cause the skin cancer-prone syndrome xeroderma pigmentosum. Truncating mutations instead cause the neurodevelopmental progeroid disorder Cockayne syndrome, but little is known about how XPG loss results in this devastating disease. We identify XPG as a partner of BRCA1 and BRCA2 in maintaining genomic stability through homologous recombination (HRR). XPG depletion causes DNA double-strand breaks, chromosomal abnormalities, cell cycle delays, defective HRR, inability to overcome replication fork stalling, and replication stress. XPG directly interacts with BRCA2, RAD51, and PALB2, and XPG depletion reduces their chromatin binding and subsequent RAD51 foci formation. Upstream in HRR, XPG interacts directly with BRCA1. Its depletion causes BRCA1 hyper-phosphorylation and persistent chromatin binding. These unexpected findings establish XPG as an HRR protein with important roles in genome stability and suggest how XPG defects produce severe clinical consequences including cancer and accelerated aging. PMID- 26833091 TI - Response to the letter concerning the article "Coronary computed tomography angiography for the assessment of SYNTAX score". PMID- 26833092 TI - Snapshots of Pluripotency. AB - Pluripotency is a unique developmental state that lays the foundation upon which the entire embryo is built. Pluripotent cells possess the unique capacity to generate, in an exquisitely defined sequence, all the distinct cell types comprising the fetal and adult organism. The discovery of pluripotent stem cells and now the ability to generate them from differentiated cells has had a profound impact on a vast array of scientific disciplines. In addition to their clinical potential as a source of therapeutic cell types, pluripotent stem cells provide scalable access to otherwise experimentally inaccessible development- and disease associated biology. Here I provide my perspective on the continuum of pluripotency in the early mammalian embryo. I also discuss how novel genomic technologies are now enabling the capture of molecular "snapshots" of the several distinct pluripotent states that stem cells undergo during this pivotal developmental period. PMID- 26833093 TI - Development of a Single-Cell Migration and Extravasation Platform through Selective Surface Modification. AB - Cell migration through three-dimensional (3D) tissue spaces is integral to many biological and pathological processes, including metastasis. Circulating tumor cells (CTCs) are phenotypically heterogeneous, and in vitro analysis of their extravasation behavior is often impeded by the inability to establish complex tissue-like extracellular matrix (ECM) environments and chemotactic gradients within microfluidic devices. We have developed a novel microfluidic strategy to manipulate surface properties of enclosed microchannels and create 3D ECM structures for real-time observation of individual migrating cells. The wettability of selective interconnected channels is controlled by a plasma pulse, enabling the incorporation of ECM exclusively within the transmigration regions. We applied this approach to collectively analyze CTC-endothelial adhesion, trans endothelial migration, and subsequent motility of breast cancer cells (MDA-MB 231) through a 3D ECM under artificial gradients of SDF-1alpha. We observed migration velocities ranging from 5.12 to 12.8 MUm/h, which closely correspond to single-cell migration in collagen blocks, but are significantly faster than the migration of cell aggregates. The compartmentalized microchannels separated by the porous ECM makes this in vitro assay versatile and suitable for a variety of applications such as inflammation studies, drug screening, and coculture interactions. PMID- 26833094 TI - Erratum to: Porcine epidemic diarrhea virus: An emerging and re-emerging epizootic swine virus. PMID- 26833096 TI - Long-term results of total knee arthroplasty in young and active patients with posterior stabilized design. AB - BACKGROUND: The aim of this study was to evaluate long-term quality and performance of cemented posterior-stabilized (PS) total knee arthroplasty (TKA) in young and active patients with gap balancing technique. METHODS: Between January 2000 and October 2001, 55 TKAs (21 rotating platform [RP] and 34 fixed bearing [FB]) in 41 patients, 60 years and younger, with University of California Los Angeles (UCLA) activity score of five and above were included in this study and prospectively followed. Clinical assessments included Western Ontario and McMaster Universities (WOMAC), Knee Society, UCLA activity score, and Patient Administered Questionnaire (PAQ). Radiographic measurements included component positioning, patellar tilt and thickness, radiolucency, loosening or osteolysis. RESULTS: At a mean follow-up of 12.3+/-0.5 years (11 to 13), there was no instability, malalignment, or patellofemoral maltracking. Sixty eight percent of patients were still participating in regular recreational activities at the final follow-up. The mean satisfaction score was 9.1+/-1.9 and 8.5+/-2.1 in RP-PS and FB-PS groups, respectively. There was no malalignment or osteolysis, no revision for osteolysis or loosening. One patient in the FB-PS group underwent open reduction and internal fixation for a peri-prosthetic fracture. Overall Kaplan Meier survivorship was 98%. CONCLUSION: The PS TKA in young and active patients can provide long-term durability and high quality of function. LEVEL OF EVIDENCE: III. PMID- 26833095 TI - mTOR masters monocytic myeloid-derived suppressor cells in mice with allografts or tumors. AB - CD11b(+) Gr1(+) myeloid-derived suppressor cells (MDSCs) play critical roles in controlling the processes of tumors, infections, autoimmunity and graft rejection. Immunosuppressive drug rapamycin (RPM), targeting on the key cellular metabolism molecule mTOR, is currently used in clinics to treat patients with allo-grafts, autoimmune diseases and tumors. However, the effect of RPM on MDSCs has not been studied. RPM significantly decreases the cell number and the immunosuppressive ability on T cells of CD11b(+) Ly6C(high) monocytic MDSCs (M MDSCs) in both allo-grafts-transplanted and tumor-bearing mice respectively. Mice with a myeloid-specific deletion of mTOR have poor M-MDSCs after grafting with allo-skin tissue or a tumor. Grafting of allo-skin or tumors significantly activates glycolysis pathways in myeloid precursor cells in bone marrow, which is inhibited by RPM or mTOR deletion. 2-deoxyglucose (2-DG), an inhibitor of the glycolytic pathway, inhibits M-MDSC differentiation from precursors, while enhancing glycolysis by metformin significantly rescues the RPM-caused deficiency of M-MDSCs. Therefore, we offer evidence supporting that mTOR is an intrinsic factor essential for the differentiation and immunosuppressive function of M MDSCs and that these metabolism-relevant medicines may impact MDSCs-mediated immunosuppression or immune tolerance induction, which is of considerable clinical importance in treating graft rejection, autoimmune diseases and cancers. PMID- 26833097 TI - Extrathoracic investigation in adult patients with isolated pulmonary langerhans cell histiocytosis. AB - BACKGROUND: An important objective on diagnosis of patients with Langerhans cell histiocytosis (LCH) is to determine the extent of disease. However, whether systematic extrathoracic investigation is needed in adult patients with clinically isolated pulmonary LCH (PLCH) has not been evaluated. METHODS: In this prospective, multicentre study, 54 consecutive patients with newly diagnosed clinically isolated PLCH were systematically evaluated at inclusion by bone imaging and blood laboratory testing to search for subclinical extrapulmonary LCH involvement. The patients were followed over a 2-year period. At each visit, they were asked about the presence of extrapulmonary manifestations of LCH. RESULTS: In the absence of bone symptoms, the skeletal X-ray survey results were normal for all but two patients who had a localised bone lesion consistent with possible LCH involvement, that remained unchanged over 2 years of follow-up. Whole-body bone scintigraphy did not add information to the plain radiography findings for the detection of asymptomatic bone involvement in isolated PLCH. Conversely, it showed nonspecific focal bone uptake in 18% of the patients, mainly corresponding to post-traumatic or degenerative abnormalities unrelated to LCH. Mild leucocytosis due to neutrophilia was observed in 22% of the patients and was not related to their smoking habits. Three patients had mild isolated lymphocytosis without haematological disease, whereas two patients had mild lymphopaenia. A mild inflammatory biological syndrome was observed in a minority of patients without infection or constitutional symptoms and was not associated with progressive disease. A substantial proportion (24.5%) of the patients had abnormal biological liver test results, including elevated liver enzymes and/or cholestasis, which were not linked to LCH involvement in this cohort. CONCLUSIONS: Obtaining a thorough history and performing comprehensive physical examination are essential for staging patients diagnosed with PLCH. In the absence of symptoms or signs suggestive of extrapulmonary LCH involvement, the systematic performing of recommended bone imaging does not appear informative. Although the observed blood laboratory abnormalities were not specifically related to LCH, performing these tests in the diagnostic workup for PLCH is useful because some of these alterations may impact patient management. TRIAL REGISTRATION: ClinicalTrials.gov: No. NCT01225601; URL: www.clinicaltrials.gov. PMID- 26833099 TI - Isocyanate Exposure Below Analytical Detection When a Paint Brush and Roller Are Used to Apply Moisture-Cure Polyurethane Paint. AB - Isocyanate exposure is known to be hazardous when polyurethane paints are applied with a spray gun, but less is known of exposure when paint is applied with a paint brush and roller. Concentrations of 1,6-hexamethylene diisocyanate (HDI) monomer and three HDI polymers were assessed when two moisture-cure polyurethane paints containing 31-35% isocyanates were applied with a paint roller and brush. Short-term 15-min samples were taken during paint application in an indoor test environment with no ventilation (n= 12); in an outdoor test environment (n= 11); and in an outdoor in-situ assessment (n= 22). The outdoor in-situ assessment involved the painting of a bus shelter and light poles at a public transit station over two night shifts. All isocyanate samples were below analytical detection. The analytical limits of detection for HDI monomer, HDI biuret, HDI isocyanurate, and HDI uretdione were 0.005, 0.84, 0.87, and 0.88 ug, respectively. The finding that isocyanate concentrations were below detection is attributed to the use of paint roller and brush which minimize paint aerosolization and the paint formulation itself which contained <1% of volatile HDI monomer. PMID- 26833100 TI - Dose-effect relationships of nucleoplasmic bridges and complex nuclear anomalies in human peripheral lymphocytes exposed to 60Co gamma-rays at a relatively low dose. AB - The dose effect between nucleoplasmic bridges (NPB) and relatively low doses of ionising radiation remains unknown. Accordingly, this study investigated the NPB frequencies in human peripheral blood lymphocytes exposed to low-dose (60)Co gamma-rays. Complex anomalies, including fused nuclei (FUS), horse-shoe nuclei (HS) and circular nuclei (CIR), which possibly originated from multiple NPBs, were also scored. Human peripheral blood samples were collected from three healthy males and irradiated with 0-1 and 0-0.4 Gy (60)Co gamma-rays. A cytokinesis-block micronucleus cytome assay was then conducted to analyse NPB, PFHC (NPB plus three complex nuclear anomalies) and micronucleus (MN) in binucleated cells. All dose-response curves followed the linear model for both NPB frequency and PFHC cell frequency. The dose-response curves between NPB frequency and absorbed dose at 0-1 and 0-0.4 Gy were y = 0.0037x + 0.0005 (R (2) = 0.979, P < 0.05) and y = 0.0043x + 0.0004 (R (2) = 0.941, P < 0.05), respectively. The dose-response curves between PFHC cell frequency and absorbed dose at 0-1 and 0-0.4 Gy were y = 0.0044x + 0.0007 (R (2) = 0.982, P < 0.05) and y = 0.0059x + 0.0005 (R (2) = 0.969, P < 0.05), respectively. The statistical significance of differences between the irradiated groups (0-0.4 Gy) and background levels of NPB, PFHC and MN were also analysed. The lowest analysable doses of NPB, PFHC and MN were 0.12, 0.08 and 0.08 Gy, respectively. In conclusion, NPBs and PFHC positively correlated with the absorbed radiation at a relatively low dose. PMID- 26833102 TI - Education to improve quality of life of people with chronic inflammatory skin conditions: a systematic review of the evidence. AB - Patient and carer education has been proposed as a way of improving health related quality of life (HRQoL) among people with chronic inflammatory skin conditions. This systematic review aimed to assess the effects of education that specifically addresses HRQoL among people with chronic inflammatory skin conditions. We searched 12 literature databases and other sources (up to July 2014). Seven randomized controlled trials (RCTs) met the review inclusion criteria. Data from these RCTs were extracted and critically appraised. Two RCTs showed that for psoriasis in adults, group-based and text message education (as adjuncts to usual care) resulted in better HRQoL and disease severity outcomes than comparators, respectively. One RCT found that group-based education for children with eczema (atopic dermatitis) and their parents resulted in greater improvements in parents' HRQoL and in the children's disease severity than no education at 12 months. The remaining RCTs evaluated an educational session for psoriasis, a website for carers of children with eczema, information on skincare and make-up use given to women with acne, and an itch-coping programme for a range of conditions, all as adjuncts to usual care. None of these RCTs found statistically significant effects on HRQoL or disease severity compared with usual care. Common features of the effective interventions were long delivery (over 6 weeks to 3 months) and delivery by a multidisciplinary team. Overall, the evidence base is currently limited and generally has an unclear risk of bias. There is a need for more large RCTs evaluating piloted and theory-based interventions. PMID- 26833103 TI - Measuring the impact of interprofessional education on collaborative practice and patient outcomes. PMID- 26833104 TI - Oral health: A vehicle to drive interprofessional education. PMID- 26833101 TI - Guidelines on vitamin D replacement in bariatric surgery: Identification and systematic appraisal. AB - INTRODUCTION: Bariatric surgery is the most effective therapeutic option to reduce weight in morbidly obese individuals, but it results in a number of mineral and vitamin deficiencies. Clinical Practice Guidelines (CPGs) attempt to balance those benefits and harms to provide guidance to physicians and patients. OBJECTIVES: We compare and evaluate the quality of the evidence and of the development process of current CPGs that provide recommendations on vitamin D replacement in patients undergoing bariatric surgery, using a validated tool. METHODS: We searched 4 databases, with no time restriction, to identify relevant and current CPGs. Two reviewers assessed eligibility and abstracted data, in duplicate. They evaluated the quality of CPGs development process using the Appraisal of Guidelines, Research, and Evaluation II (AGREE II) tool that consists of 6 domains. A content expert verified those assessments. RESULTS: We identified 3 eligible CPGs: (1) the Endocrine Society (ES) guidelines (2010); (2) the American Association of Clinical Endocrinologists (AACE), The Obesity Society (TOS), and the American Society for Metabolic & Bariatric Surgery (ASMBS) guidelines (update 2013); and (3) the Interdisciplinary European (IE) guidelines on Metabolic and Bariatric Surgery (latest update 2014). The ES and the AACE/TOS/ASMBS guidelines recommended high doses of vitamin D, varying from 3000IU daily to 50,000IU 1-3 times weekly. Vitamin D doses were not mentioned in the IE guidelines. The recommendations were based on a low quality of evidence, if any, or limited to a single high quality trial, for some outcomes. In terms of quality, only the IE guidelines described their search methodology but none of the CPGs provided details on evidence selection and appraisal. None of the three CPGs rigorously assessed the preferences of the target population, resource implications, and the applicability of these guidelines. According to the AGREE II tool, we rated the ES guidelines as average in quality, and the other two as low in quality. CONCLUSION: Current CPGs recommendations on vitamin D supplementation in bariatric surgery differ between societies. They do not fulfill criteria for optimal guideline development, in part possibly due to limited resources, and are based on expert opinion. Thus, the pressing need for high quality randomized trials to inform CPGs, to be developed based on recommended standards. PMID- 26833105 TI - Exploring the importance of team psychological safety in the development of two interprofessional teams. AB - It has been previously demonstrated that interactions within interprofessional teams are characterised by effective communication, shared decision-making, and knowledge sharing. This article outlines aspects of an action research study examining the emergence of these characteristics within change management teams made up of nurses, general practitioners, physiotherapists, care assistants, a health and safety officer, and a client at two residential care facilities for older people in Ireland. The theoretical concept of team psychological safety (TPS) is utilised in presenting these characteristics. TPS has been defined as an atmosphere within a team where individuals feel comfortable engaging in discussion and reflection without fear of censure. Study results suggest that TPS was an important catalyst in enhancing understanding and power sharing across professional boundaries and thus in the development of interprofessional teamwork. There were differences between the teams. In one facility, the team developed many characteristics of interprofessional teamwork while at the other there was only a limited shift. Stability in team membership and organisational norms relating to shared decision-making emerged as particularly important in accounting for differences in the development of TPS and interprofessional teamwork. PMID- 26833106 TI - A critical narrative analysis of shared decision-making in acute inpatient mental health care. AB - Shared decision-making (SDM) is a high priority in healthcare policy and is complementary to the recovery philosophy in mental health care. This agenda has been operationalised within the Values-Based Practice (VBP) framework, which offers a theoretical and practical model to promote democratic interprofessional approaches to decision-making. However, these are limited by a lack of recognition of the implications of power implicit within the mental health system. This study considers issues of power within the context of decision making and examines to what extent decisions about patients' care on acute in patient wards are perceived to be shared. Focus groups were conducted with 46 mental health professionals, service users, and carers. The data were analysed using the framework of critical narrative analysis (CNA). The findings of the study suggested each group constructed different identity positions, which placed them as inside or outside of the decision-making process. This reflected their view of themselves as best placed to influence a decision on behalf of the service user. In conclusion, the discourse of VBP and SDM needs to take account of how differentials of power and the positioning of speakers affect the context in which decisions take place. PMID- 26833107 TI - Attitudes towards physician-nurse collaboration in a primary care team-based setting: Survey-based research conducted in the chronic care units of the Tuscany region of Italy. AB - Across the world, multidisciplinary teamwork has become an essential component in the care of patients with chronic conditions--the Chronic Care Units (CCUs) in the Italian region of Tuscany are no exception to this new era of collaboration. We sought to explore the attitudes towards collaboration of general practitioners (GPs) and nurses within the CCUs using the Jefferson Scale of Attitudes towards Physician-Nurse Collaboration (JSAPNC). The survey was sent electronically to 218 GPs and 46 nurses of 23 CCUs in two Local Health Authorities of Tuscany. A higher JSAPNC score is indicative of a more positive attitude towards physician-nurse collaboration. JSAPNC scores were calculated for both totals and by three factors: "shared education and collaboration," "caring versus curing," and "physician authority." A total of 133 healthcare professionals (94 GPs and 39 nurses) responded (response rate = 51.5%). Nurses reported significantly more positive attitudes towards collaboration than GPs (52.5 vs. 44.0, p < 0.01). This trend was also found in each of the three factors. This information adds to the scarce literature on nurse-physician collaboration in the primary care setting and highlights the need for considerable improvement given the rise of team-based outpatient care models. PMID- 26833108 TI - Examining the influence of professional identity formation on the attitudes of students towards interprofessional collaboration. AB - An expectation of introductory interprofessional education (IPE) is improvement in attitudes towards other professions. However, the theory surrounding professional identity formation suggests this expectation may be premature. The objective of this study was to quantify first-year health professional students' attitudes towards their own and other professions and to investigate the relationship between strength of professional identity and attitudes towards other professions and interprofessional learning. Using a pre/post-test design, researchers administered the Readiness for Interprofessional Learning Scale (RIPLS) and the Interdisciplinary Education Perception Scale (IEPS) to 864 first year healthcare students in the Academic Health Center (AHC) at the University of Minnesota. The findings showed a decline in student attitudes towards their own and other professions. Additionally, a positive correlation between a weakened professional identity and readiness for interprofessional learning was demonstrated. This study found that an introductory IPE course did not positively affect student attitudes towards other professions, or strengthen professional identity or readiness for interprofessional learning. Analysis of the findings support the successive stages of professional identity formation. PMID- 26833109 TI - A cross-institutional analysis of Australian undergraduate paramedic students' attitudes towards interprofessional collaboration. AB - Interprofessional collaboration (IPC) continues to gain much momentum with recognition and evidence that improved communication and collaboration between healthcare workers leads to better delivery and access to care. The objective of this study was to examine the self-reported IPC among Australian paramedic undergraduate students over two years. A two-year cross-sectional study involving undergraduate paramedic students from multiple Australian Universities was undertaken. Students' IPC levels were measured using the Interdisciplinary Education Perception Scale (IEPS). Responses were collected from 1,264 students during the 2011 and 2012 academic years. During the study females tended to outnumber males enrolled in paramedic studies across all universities, which was consistent across 2011 and 2012 (overall, n = 748 or 59.2% and n = 516 or 40.8% for females and males, respectively). Factor results revealed mean = 23.63 (Competence/Autonomy), mean = 9.65 (Perceived need for Cooperation), and mean = 23.78 (Perception of Actual Cooperation). There were no differences in self reported perceptions between students assessed in 2011 and 2012 for any of the three factors. The current study provides the first multi-institutional normative data for paramedic students for the IEPS within Australia. Initial findings tend to suggest that paramedic undergraduates are positive about the concept of IPC and their ability to work as part of a collaborative healthcare team. PMID- 26833110 TI - Understanding interprofessional education as an intergroup encounter: The use of contact theory in programme planning. AB - A key underlying assumption of interprofessional education (IPE) is that if the professions are brought together they have the opportunity to learn about each other and dispel the negative stereotypes which are presumed to hamper interprofessional collaboration in practice. This article explores the application of contact theory in IPE with reference to eight evaluation studies (1995-2012) which adopted this theoretical perspective. It proposes that educators should pay explicit attention to an intergroup perspective in designing IPE programmes and specifically to the "contact variables" identified by social psychologists studying intergroup encounters. This would increase the chances of the planned contact having a positive effect on attitude change. PMID- 26833111 TI - Impact of peer pressure on accuracy of reporting vital signs: An interprofessional comparison between nursing and medical students. AB - The hierarchical relationship between nursing and medicine has long been known, yet its direct influence on procedural tasks has yet to be considered. Drawing on the theory of conformity from social psychology, we suggest that nursing students are likely to report incorrect information in response to subtle social pressures imposed by medical students. Second-year medical and third-year nursing students took vital signs readings from a patient simulator. In a simulation exercise, three actors, posing as medical students, and one nursing student participant all took a total of three rounds of vital signs on a high-fidelity patient simulator. In the first two rounds the three actors individually stated the same correct vital signs values, and on the third round the three actors individually stated the same incorrect vital sign values. This same procedure was repeated with actors posing as nursing students, and one medical student. A two-way analysis of variance (ANOVA) revealed that nursing student participants (M = 2.84; SD = 1.24) reported a higher number of incorrect vital signs than did medical student participants (M = 2.13; SD = 1.07), F (1,100) = 5.51, p = 0.021 (Cohen's d = 0.61). The study indicated that social pressure may prevent nursing students from questioning incorrect information within interprofessional environments, potentially affecting quality of care. PMID- 26833112 TI - Interprofessional student-led clinics: An innovative approach to the support of older people in the community. AB - A student-led clinic was established to provide both an opportunity for interprofessional student education and the delivery of patient care. Fourth- or final-year students from allied health, medicine, and nursing worked in mixed professional teams to review the health of community-dwelling older people recently discharged from acute hospitals. We designed a prospective evaluation to study services delivered and their perceived value. Between 2011 and 2013, 98 patients who had been recently discharged from an acute medical ward attended the clinic. Students generated referrals for many services, most commonly physiotherapy, podiatry, and review by a general practitioner. Patient perceptions of consultations, measured with the Patient Experience Questionnaire, were gathered from 61 out of 96 (64%) participants and were generally favourable, with the communication domain scoring the most favourably. Undergraduate students, working in mixed professional teams, are able to deliver a useful additional health promotion service to older people. PMID- 26833098 TI - Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels. AB - Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 * 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health. PMID- 26833113 TI - Competences for enhancing interprofessional collaboration in a paediatrics setting: Enabling and hindering factors. AB - In 2011 an interprofessional educational programme called "Pediatric systematic assessment and communication for preventing emergencies" designed to increase clinical staff's competence in treating sick children was introduced in one paediatrics department in Norway. To elicit an in-depth understanding of the perceptions of clinical staff about the programme and enact adjustments according to identified enabling and hindering factors for learning, nurses and paediatricians were invited to participate in focus group interviews. The interviews were analysed by content analysis. Enabling factors for learning included improved interprofessional collaboration and positive feedback on performance. Hindering factors included perceptions that the programme was redundant and the fact that collaborating departments, such as the surgical departments, were not familiar with the programme. Peer learning, more interprofessional learning activities, and the fostering of a learning organization were suggestions for sustained learning. Based on the results of the study we have now included collaborating departments in the programme. PMID- 26833114 TI - Immunoglobulin G Expression in Human Sperm and Possible Functional Significance. AB - Immunoglobulin G (IgG), the major molecule of the immune system, which was traditionally thought to be produced by differentiated B-lymphocytes, had recently been found in non-immune cells including spermatozoa of rabbit testis. To study if human sperms could produce IgG that might play a role in fertilization, we employed immunofluorescent staining, Western blot, in situ hybridization, RT-PCR (reverse transcription polymerase chain reaction) and immunoelectron microscope and found that human sperms were capable of synthesizing IgG. IgG protein and mRNA were detected in the cytoplasm, mainly the neck region of the sperm and IgG immunoreactivity was found to cover the entire sperm cell. The essential enzymes necessary for IgG synthesis and class switching, RAG1 (recombination activating gene 1), RAG2 (recombination activating gene 2) and AID (activation-induced cytidine deaminase), were also detected in the sperm cells. Furthermore, we found that anti-IgG antibody could inhibit sperm from penetrating Zona-free hamster egg with statistical significance. These discoveries suggested that immunoglobulin G could be produced by human sperms and it might play a role during fertilization. PMID- 26833116 TI - Pragmatic Clinical Trials: Implementation Opportunity, or Just Another Fad? PMID- 26833115 TI - In Pursuit of the Ever-Expanding Shoreline. PMID- 26833117 TI - Unpacking Payment Bundles. PMID- 26833119 TI - Targeting the IL-33/IL-13 Axis for Respiratory Viral Infections. AB - Lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are highly prevalent worldwide. One of the major factors that limits the efficacy of current medication in these patients are viral infections, leading to exacerbations of symptoms and decreased quality of life. Current pharmacological strategies targeting virus-induced lung disease are problematic due to antiviral resistance and the requirement for strain-specific vaccination. Thus, new therapeutic strategies are urgently required. In this Opinion article, we provide state-of-the-art evidence from humans and preclinical animal models implicating the interleukin (IL)-33/IL-13 axis in virus-induced lung disease. Thus, targeting the IL-33/IL-13 axis may be a feasible way to overcome the limitations of current therapy used to treat virus-induced exacerbations of lung disease. PMID- 26833118 TI - New Technologies for Elucidating Opioid Receptor Function. AB - Recent advances in technology, including high resolution crystal structures of opioid receptors, novel chemical tools, and new genetic approaches have provided an unparalleled palette of tools for deconstructing opioid receptor actions in vitro and in vivo. Here we provide a brief description of our understanding of opioid receptor function from both molecular and atomic perspectives, as well as their role in neural circuits in vivo. We then show how insights into the molecular details of opioid actions can facilitate the creation of functionally selective (biased) and photoswitchable opioid ligands. Finally, we describe how newly engineered opioid receptor-based chemogenetic and optogenetic tools, and new mouse lines, are expanding and transforming our understanding of opioid function and, perhaps, paving the way for new therapeutics. PMID- 26833120 TI - MCPIP1 Selectively Destabilizes Transcripts Associated with an Antiapoptotic Gene Expression Program in Breast Cancer Cells That Can Elicit Complete Tumor Regression. AB - The ability of cancer cells to evade apoptosis is dictated by a shift in the balance between proapoptotic and antiapoptotic gene expression programs. Monocyte chemotactic protein-induced protein 1 (MCPIP1) is a zinc-finger RNA binding protein with important roles in mediating inflammatory responses. Overexpression of MCPIP1 in different cancer cell types has been implicated in eliciting an antitumor response, but a direct role of MCPIP1 in apoptosis has not been established. In this study, we demonstrate that MCPIP1 functions as a potent tumor suppressor that induces apoptosis of breast tumor cells by selectively enhancing mRNA decay of antiapoptotic gene transcripts, including Bcl2L1, Bcl2A1, RelB, Birc3, and Bcl3. Mechanistically, MCPIP1 physically interacted with a stem loop structure in the 3' untranslated region of these transcripts through its PIN domain, causing mRNA destabilization. Furthermore, we found that MCPIP1 expression was repressed in breast tumor cells, and overexpression of MCPIP1 induced apoptosis, whereas its depletion enhanced cancer cell proliferation. Moreover, MCPIP1 induction in vivo resulted in complete regression of established tumors and a significant reduction in metastatic disease. Notably, low MCPIP1 expression in tumor samples from breast cancer patients was strongly associated with poor survival over 13 years of follow-up. Collectively, our results highlight that MCPIP1 is a new tumor suppressor in breast cancer that induces cell death by tipping the balance in favor of proapoptotic gene expression. PMID- 26833122 TI - The Cancer Stem Cell Fraction in Hierarchically Organized Tumors Can Be Estimated Using Mathematical Modeling and Patient-Specific Treatment Trajectories. AB - Many tumors are hierarchically organized and driven by a subpopulation of tumor initiating cells (TIC), or cancer stem cells. TICs are uniquely capable of recapitulating the tumor and are thought to be highly resistant to radio- and chemotherapy. Macroscopic patterns of tumor expansion before treatment and tumor regression during treatment are tied to the dynamics of TICs. Until now, the quantitative information about the fraction of TICs from macroscopic tumor burden trajectories could not be inferred. In this study, we generated a quantitative method based on a mathematical model that describes hierarchically organized tumor dynamics and patient-derived tumor burden information. The method identifies two characteristic equilibrium TIC regimes during expansion and regression. We show that tumor expansion and regression curves can be leveraged to infer estimates of the TIC fraction in individual patients at detection and after continued therapy. Furthermore, our method is parameter-free; it solely requires the knowledge of a patient's tumor burden over multiple time points to reveal microscopic properties of the malignancy. We demonstrate proof of concept in the case of chronic myeloid leukemia (CML), wherein our model recapitulated the clinical history of the disease in two independent patient cohorts. On the basis of patient-specific treatment responses in CML, we predict that after one year of targeted treatment, the fraction of TICs increases 100-fold and continues to increase up to 1,000-fold after 5 years of treatment. Our novel framework may significantly influence the implementation of personalized treatment strategies and has the potential for rapid translation into the clinic. Cancer Res; 76(7); 1705-13. (c)2016 AACR. PMID- 26833121 TI - Bidirectional Notch Signaling and Osteocyte-Derived Factors in the Bone Marrow Microenvironment Promote Tumor Cell Proliferation and Bone Destruction in Multiple Myeloma. AB - In multiple myeloma, an overabundance of monoclonal plasma cells in the bone marrow induces localized osteolytic lesions that rarely heal due to increased bone resorption and suppressed bone formation. Matrix-embedded osteocytes comprise more than 95% of bone cells and are major regulators of osteoclast and osteoblast activity, but their contribution to multiple myeloma growth and bone disease is unknown. Here, we report that osteocytes in a mouse model of human MM physically interact with multiple myeloma cells in vivo, undergo caspase-3 dependent apoptosis, and express higher RANKL (TNFSF11) and sclerostin levels than osteocytes in control mice. Mechanistic studies revealed that osteocyte apoptosis was initiated by multiple myeloma cell-mediated activation of Notch signaling and was further amplified by multiple myeloma cell-secreted TNF. The induction of apoptosis increased osteocytic Rankl expression, the osteocytic Rankl/Opg (TNFRSF11B) ratio, and the ability of osteocytes to attract osteoclast precursors to induce local bone resorption. Furthermore, osteocytes in contact with multiple myeloma cells expressed high levels of Sost/sclerostin, leading to a reduction in Wnt signaling and subsequent inhibition of osteoblast differentiation. Importantly, direct contact between osteocytes and multiple myeloma cells reciprocally activated Notch signaling and increased Notch receptor expression, particularly Notch3 and 4, stimulating multiple myeloma cell growth. These studies reveal a previously unknown role for bidirectional Notch signaling that enhances MM growth and bone disease, suggesting that targeting osteocyte multiple myeloma cell interactions through specific Notch receptor blockade may represent a promising treatment strategy in multiple myeloma. PMID- 26833123 TI - The Ephrin-A1/EPHA2 Signaling Axis Regulates Glutamine Metabolism in HER2 Positive Breast Cancer. AB - Dysregulation of receptor tyrosine kinases (RTK) contributes to cellular transformation and cancer progression by disrupting key metabolic signaling pathways. The EPHA2 RTK is overexpressed in aggressive forms of breast cancer, including the HER2(+) subtype, and correlates with poor prognosis. However, the role of EPHA2 in tumor metabolism remains unexplored. In this study, we used in vivo and in vitro models of HER2-overexpressing breast cancer to investigate the mechanisms by which EPHA2 ligand-independent signaling promotes tumorigenesis in the absence of its prototypic ligand, ephrin-A1. We demonstrate that ephrin-A1 loss leads to upregulated glutamine metabolism and lipid accumulation that enhanced tumor growth. Global metabolic profiling of ephrin-A1-null, HER2 overexpressing mammary tumors revealed a significant increase in glutaminolysis, a critical metabolic pathway that generates intermediates for lipogenesis. Pharmacologic inhibition of glutaminase activity reduced tumor growth in both ephrin-A1-depleted and EPHA2-overexpressing tumor allografts in vivo Mechanistically, we show that the enhanced proliferation and glutaminolysis in the absence of ephrin-A1 were attributed to increased RhoA-dependent glutaminase activity. EPHA2 depletion or pharmacologic inhibition of Rho, glutaminase, or fatty acid synthase abrogated the increased lipid content and proliferative effects of ephrin-A1 knockdown. Together, these findings highlight a novel, unsuspected connection between the EPHA2/ephrin-A1 signaling axis and tumor metabolism, and suggest potential new therapeutic targets in cancer subtypes exhibiting glutamine dependency. Cancer Res; 76(7); 1825-36. (c)2016 AACR. PMID- 26833124 TI - Cystine Deprivation Triggers Programmed Necrosis in VHL-Deficient Renal Cell Carcinomas. AB - Oncogenic transformation may reprogram tumor metabolism and render cancer cells addicted to extracellular nutrients. Deprivation of these nutrients may therefore represent a therapeutic opportunity, but predicting which nutrients cancer cells become addicted remains difficult. Here, we performed a nutrigenetic screen to determine the phenotypes of isogenic pairs of clear cell renal cancer cells (ccRCC), with or without VHL, upon the deprivation of individual amino acids. We found that cystine deprivation triggered rapid programmed necrosis in VHL deficient cell lines and primary ccRCC tumor cells, but not in VHL-restored counterparts. Blocking cystine uptake significantly delayed xenograft growth of ccRCC. Importantly, cystine deprivation triggered similar metabolic changes regardless of VHL status, suggesting that metabolic responses alone are not sufficient to explain the observed distinct fates of VHL-deficient and restored cells. Instead, we found that increased levels of TNFalpha associated with VHL loss forced VHL-deficient cells to rely on intact RIPK1 to inhibit apoptosis. However, the preexisting elevation in TNFalpha expression rendered VHL-deficient cells susceptible to necrosis triggered by cystine deprivation. We further determined that reciprocal amplification of the Src-p38 (MAPK14)-Noxa (PMAIP1) signaling and TNFalpha-RIP1/3 (RIPK1/RIPK3)-MLKL necrosis pathways potentiated cystine-deprived necrosis. Together, our findings reveal that cystine deprivation in VHL-deficient RCCs presents an attractive therapeutic opportunity that may bypass the apoptosis-evading mechanisms characteristic of drug-resistant tumor cells. Cancer Res; 76(7); 1892-903. (c)2016 AACR. PMID- 26833125 TI - An Integrated Analysis of Heterogeneous Drug Responses in Acute Myeloid Leukemia That Enables the Discovery of Predictive Biomarkers. AB - Many promising new cancer drugs proceed through preclinical testing and early phase trials only to fail in late-stage clinical testing. Thus, improved models that better predict survival outcomes and enable the development of biomarkers are needed to identify patients most likely to respond to and benefit from therapy. Here, we describe a comprehensive approach in which we incorporated biobanking, xenografting, and multiplexed phospho-flow (PF) cytometric profiling to study drug response and identify predictive biomarkers in acute myeloid leukemia (AML) patients. To test the efficacy of our approach, we evaluated the investigational JAK2 inhibitor fedratinib (FED) in 64 patient samples. FED robustly reduced leukemia in mouse xenograft models in 59% of cases and was also effective in limiting the protumorigenic activity of leukemia stem cells as shown by serial transplantation assays. In parallel, PF profiling identified FED mediated reduction in phospho-STAT5 (pSTAT5) levels as a predictive biomarker of in vivo drug response with high specificity (92%) and strong positive predictive value (93%). Unexpectedly, another JAK inhibitor, ruxolitinib (RUX), was ineffective in 8 of 10 FED-responsive samples. Notably, this outcome could be predicted by the status of pSTAT5 signaling, which was unaffected by RUX treatment. Consistent with this observed discrepancy, PF analysis revealed that FED exerted its effects through multiple JAK2-independent mechanisms. Collectively, this work establishes an integrated approach for testing novel anticancer agents that captures the inherent variability of response caused by disease heterogeneity and in parallel, facilitates the identification of predictive biomarkers that can help stratify patients into appropriate clinical trials. PMID- 26833126 TI - HER2 Signaling Drives DNA Anabolism and Proliferation through SRC-3 Phosphorylation and E2F1-Regulated Genes. AB - Approximately 20% of early-stage breast cancers display amplification or overexpression of the ErbB2/HER2 oncogene, conferring poor prognosis and resistance to endocrine therapy. Targeting HER2(+) tumors with trastuzumab or the receptor tyrosine kinase (RTK) inhibitor lapatinib significantly improves survival, yet tumor resistance and progression of metastatic disease still develop over time. Although the mechanisms of cytosolic HER2 signaling are well studied, nuclear signaling components and gene regulatory networks that bestow therapeutic resistance and limitless proliferative potential are incompletely understood. Here, we use biochemical and bioinformatic approaches to identify effectors and targets of HER2 transcriptional signaling in human breast cancer. Phosphorylation and activity of the Steroid Receptor Coactivator-3 (SRC-3) is reduced upon HER2 inhibition, and recruitment of SRC-3 to regulatory elements of endogenous genes is impaired. Transcripts regulated by HER2 signaling are highly enriched with E2F1 binding sites and define a gene signature associated with proliferative breast tumor subtypes, cell-cycle progression, and DNA replication. We show that HER2 signaling promotes breast cancer cell proliferation through regulation of E2F1-driven DNA metabolism and replication genes together with phosphorylation and activity of the transcriptional coactivator SRC-3. Furthermore, our analyses identified a cyclin-dependent kinase (CDK) signaling node that, when targeted using the CDK4/6 inhibitor palbociclib, defines overlap and divergence of adjuvant pharmacologic targeting. Importantly, lapatinib and palbociclib strictly block de novo synthesis of DNA, mostly through disruption of E2F1 and its target genes. These results have implications for rational discovery of pharmacologic combinations in preclinical models of adjuvant treatment and therapeutic resistance. PMID- 26833128 TI - Abscopal Benefits of Localized Radiotherapy Depend on Activated T-cell Trafficking and Distribution between Metastatic Lesions. AB - It remains unclear how localized radiotherapy for cancer metastases can occasionally elicit a systemic antitumor effect, known as the abscopal effect, but historically, it has been speculated to reflect the generation of a host immunotherapeutic response. The ability to purposefully and reliably induce abscopal effects in metastatic tumors could meet many unmet clinical needs. Here, we describe a mathematical model that incorporates physiologic information about T-cell trafficking to estimate the distribution of focal therapy-activated T cells between metastatic lesions. We integrated a dynamic model of tumor-immune interactions with systemic T-cell trafficking patterns to simulate the development of metastases. In virtual case studies, we found that the dissemination of activated T cells among multiple metastatic sites is complex and not intuitively predictable. Furthermore, we show that not all metastatic sites participate in systemic immune surveillance equally, and therefore the success in triggering the abscopal effect depends, at least in part, on which metastatic site is selected for localized therapy. Moreover, simulations revealed that seeding new metastatic sites may accelerate the growth of the primary tumor, because T-cell responses are partially diverted to the developing metastases, but the removal of the primary tumor can also favor the rapid growth of preexisting metastatic lesions. Collectively, our work provides the framework to prospectively identify anatomically defined focal therapy targets that are most likely to trigger an immune-mediated abscopal response and therefore may inform personalized treatment strategies in patients with metastatic disease. PMID- 26833127 TI - STK11/LKB1 Deficiency Promotes Neutrophil Recruitment and Proinflammatory Cytokine Production to Suppress T-cell Activity in the Lung Tumor Microenvironment. AB - STK11/LKB1 is among the most commonly inactivated tumor suppressors in non-small cell lung cancer (NSCLC), especially in tumors harboring KRAS mutations. Many oncogenes promote immune escape, undermining the effectiveness of immunotherapies, but it is unclear whether the inactivation of tumor suppressor genes, such as STK11/LKB1, exerts similar effects. In this study, we investigated the consequences of STK11/LKB1 loss on the immune microenvironment in a mouse model of KRAS-driven NSCLC. Genetic ablation of STK11/LKB1 resulted in accumulation of neutrophils with T-cell-suppressive effects, along with a corresponding increase in the expression of T-cell exhaustion markers and tumor promoting cytokines. The number of tumor-infiltrating lymphocytes was also reduced in LKB1-deficient mouse and human tumors. Furthermore, STK11/LKB1 inactivating mutations were associated with reduced expression of PD-1 ligand PD L1 in mouse and patient tumors as well as in tumor-derived cell lines. Consistent with these results, PD-1-targeting antibodies were ineffective against Lkb1 deficient tumors. In contrast, treating Lkb1-deficient mice with an IL6 neutralizing antibody or a neutrophil-depleting antibody yielded therapeutic benefits associated with reduced neutrophil accumulation and proinflammatory cytokine expression. Our findings illustrate how tumor suppressor mutations can modulate the immune milieu of the tumor microenvironment, and they offer specific implications for addressing STK11/LKB1-mutated tumors with PD-1-targeting antibody therapies. PMID- 26833130 TI - Sorting of Single Biomolecules based on Fourier Polar Representation of Surface Enhanced Raman Spectra. AB - Surface enhanced Raman scattering (SERS) spectroscopy becomes increasingly used in biosensors for its capacity to detect and identify single molecules. In practice, a large number of SERS spectra are acquired and reliable ranking methods are thus essential for analysing all these data. Supervised classification strategies, which are the most effective methods, are usually applied but they require pre-determined models or classes. In this work, we propose to sort SERS spectra in unknown groups with an alternative strategy called Fourier polar representation. This non-fitting method based on simple Fourier sine and cosine transforms produces a fast and graphical representation for sorting SERS spectra with quantitative information. The reliability of this method was first investigated theoretically and numerically. Then, its performances were tested on two concrete biological examples: first with single amino-acid molecule (cysteine) and then with a mixture of three distinct odorous molecules. The benefits of this Fourier polar representation were highlighted and compared to the well-established statistical principal component analysis method. PMID- 26833129 TI - Inhibition of MUC1-C Suppresses MYC Expression and Attenuates Malignant Growth in KRAS Mutant Lung Adenocarcinomas. AB - Dysregulation of MYC expression is a hallmark of cancer, but the development of agents that target MYC has remained challenging. The oncogenic MUC1-C transmembrane protein is, like MYC, aberrantly expressed in diverse human cancers. The present studies demonstrate that MUC1-C induces MYC expression in KRAS mutant non-small cell lung cancer (NSCLC) cells, an effect that can be suppressed by targeting MUC1-C via shRNA silencing, CRISPR editing, or pharmacologic inhibition with GO-203. MUC1-C activated the WNT/beta-catenin (CTNNB1) pathway and promoted occupancy of MUC1-C/beta-catenin/TCF4 complexes on the MYC promoter. MUC1-C also promoted the recruitment of the p300 histone acetylase (EP300) and, in turn, induced histone H3 acetylation and activation of MYC gene transcription. We also show that targeting MUC1-C decreased the expression of key MYC target genes essential for the growth and survival of NSCLC cells, such as TERT and CDK4. Based on these results, we found that the combination of GO-203 and the BET bromodomain inhibitor JQ1, which targets MYC transcription, synergistically suppressed MYC expression and cell survival in vitro as well as tumor xenograft growth. Furthermore, MUC1 expression significantly correlated with that of MYC and its target genes in human KRAS mutant NSCLC tumors. Taken together, these findings suggest a therapeutic approach for targeting MYC-dependent cancers and provide the framework for the ongoing clinical studies addressing the efficacy of MUC1-C inhibition in solid tumors. PMID- 26833131 TI - Deficiency in DGCR8-dependent canonical microRNAs causes infertility due to multiple abnormalities during uterine development in mice. AB - DGCR8 is an RNA-binding protein that interacts with DROSHA to produce pre microRNA in the nucleus, while DICER generates not only mature microRNA, but also endogenous small interfering RNAs in the cytoplasm. Here, we produced Dgcr8 conditional knock-out mice using progesterone receptor (PR)-Cre (Dgcr8(d/d)) and demonstrated that canonical microRNAs dependent on the DROSHA-DGCR8 complex are required for uterine development as well as female fertility in mice. Adult Dgcr8(d/d) females neither underwent regular reproductive cycles nor produced pups, whereas administration of exogenous gonadotropins induced normal ovulation in these mice. Interestingly, immune cells associated with acute inflammation aberrantly infiltrated into reproductive organs of pregnant Dgcr8(d/d) mice. Regarding uterine development, multiple uterine abnormalities were noticeable at 4 weeks of age when PR is significantly increased, and the severity of these deformities increased over time. Gland formation and myometrial layers were significantly reduced, and the stromal cell compartment did not expand and became atrophic during uterine development in these mice. These results were consistent with aberrantly reduced stromal cell proliferation and completely failed decidualization. Collectively, we suggest that DGCR8-dependent canonical microRNAs are essential for uterine development and physiological processes such as proper immune modulation, reproductive cycle, and steroid hormone responsiveness in mice. PMID- 26833132 TI - Impact of rotavirus vaccination on coverage and timing of pentavalent vaccination - Experience from 2 Latin American countries. AB - We examined the coverage and timing of rotavirus vaccination and the impact of rotavirus vaccine introduction on coverage and timing of the pentavalent vaccine. We used data from the Demographic and Health Surveys in Honduras (2011/2012) and Peru (2012). The samples were divided into 2 subcohorts: children born before and after the introduction of rotavirus vaccine. We compared coverage and timing of the pentavalent vaccine in the aforementioned subcohorts. Coverage with the first and second doses of rotavirus vaccination was 95% (95% confidence intervals: 93 97%) and 91% (89-95%) in Honduras and 79% (77-82%) and 72% (69-75%) in Peru, respectively. Coverage increased in both countries over the years. The proportion of children vaccinated according to age-appropriate vaccination schedules varied between 67% (second dose of rotavirus vaccinations in Peru) and 89% (first dose of rotavirus vaccination in Honduras). Coverage with the first and second doses of pentavalent vaccination remained constant over the years in Honduras, while in Peru there was a significant increase in coverage over the years (p for trend, <0.0001). In both countries, timing of pentavalent vaccination was better in post rota-cohorts than in pre-rota-cohorts. Since its introduction, coverage of rotavirus vaccination has improved over time in both countries. An introduction of rotavirus vaccination in both countries appears to have improved the coverage and timing of other similarly scheduled vaccinations. PMID- 26833133 TI - Unexpected Giant-Gap Quantum Spin Hall Insulator in Chemically Decorated Plumbene Monolayer. AB - Quantum spin Hall (QSH) effect of two-dimensional (2D) materials features edge states that are topologically protected from backscattering by time-reversal symmetry. However, the major obstacles to the application for QSH effect are the lack of suitable QSH insulators with a large bulk gap. Here, we predict a novel class of 2D QSH insulators in X-decorated plumbene monolayers (PbX; X = H, F, Cl, Br, I) with extraordinarily giant bulk gaps from 1.03 eV to a record value of 1.34 eV. The topological characteristic of PbX mainly originates from s-p(x,y) band inversion related to the lattice symmetry, while the effect of spin-orbital coupling (SOC) is only to open up a giant gap. Their QSH states are identified by nontrivial topological invariant Z2 = 1, as well as a single pair of topologically protected helical edge states locating inside the bulk gap. Noticeably, the QSH gaps of PbX are tunable and robust via external strain. We also propose high-dielectric-constant BN as an ideal substrate for the experimental realization of PbX, maintaining its nontrivial topology. These novel QSH insulators with giant gaps are a promising platform to enrich topological phenomena and expand potential applications at high temperature. PMID- 26833135 TI - Axonal Filtering Allows Reliable Output during Dendritic Plateau-Driven Complex Spiking in CA1 Neurons. AB - In CA1 pyramidal neurons, correlated inputs trigger dendritic plateau potentials that drive neuronal plasticity and firing rate modulation. Given the strong electrotonic coupling between soma and axon, the >25 mV depolarization associated with the plateau could propagate through the axon to influence action potential initiation, propagation, and neurotransmitter release. We examined this issue in brain slices, awake mice, and a computational model. Despite profoundly inactivating somatic and proximal axon Na(+) channels, plateaus evoked action potentials that recovered to full amplitude in the distal axon (>150 MUm) and triggered neurotransmitter release similar to regular spiking. This effect was due to strong attenuation of plateau depolarizations by axonal K(+) channels, allowing full axon repolarization and Na(+) channel deinactivation. High-pass filtering of dendritic plateaus by axonal K(+) channels should thus enable accurate transmission of gain-modulated firing rates, allowing neuronal firing to be efficiently read out by downstream regions as a simple rate code. PMID- 26833134 TI - Estrogens Suppress a Behavioral Phenotype in Zebrafish Mutants of the Autism Risk Gene, CNTNAP2. AB - Autism spectrum disorders (ASDs) are a group of devastating neurodevelopmental syndromes that affect up to 1 in 68 children. Despite advances in the identification of ASD risk genes, the mechanisms underlying ASDs remain unknown. Homozygous loss-of-function mutations in Contactin Associated Protein-like 2 (CNTNAP2) are strongly linked to ASDs. Here we investigate the function of Cntnap2 and undertake pharmacological screens to identify phenotypic suppressors. We find that zebrafish cntnap2 mutants display GABAergic deficits, particularly in the forebrain, and sensitivity to drug-induced seizures. High-throughput behavioral profiling identifies nighttime hyperactivity in cntnap2 mutants, while pharmacological testing reveals dysregulation of GABAergic and glutamatergic systems. Finally, we find that estrogen receptor agonists elicit a behavioral fingerprint anti-correlative to that of cntnap2 mutants and show that the phytoestrogen biochanin A specifically reverses the mutant behavioral phenotype. These results identify estrogenic compounds as phenotypic suppressors and illuminate novel pharmacological pathways with relevance to autism. PMID- 26833136 TI - Pathway-Specific Remodeling of Thalamostriatal Synapses in Parkinsonian Mice. AB - Movement suppression in Parkinson's disease (PD) is thought to arise from increased efficacy of the indirect pathway basal ganglia circuit, relative to the direct pathway. However, the underlying pathophysiological mechanisms remain elusive. To examine whether changes in the strength of synaptic inputs to these circuits contribute to this imbalance, we obtained paired whole-cell recordings from striatal direct- and indirect-pathway medium spiny neurons (dMSNs and iMSNs) and optically stimulated inputs from sensorimotor cortex or intralaminar thalamus in brain slices from control and dopamine-depleted mice. We found that dopamine depletion selectively decreased synaptic strength at thalamic inputs to dMSNs, suggesting that thalamus drives asymmetric activation of basal ganglia circuitry underlying parkinsonian motor impairments. Consistent with this hypothesis, in vivo chemogenetic and optogenetic inhibition of thalamostriatal terminals reversed motor deficits in dopamine-depleted mice. These results implicate thalamostriatal projections in the pathophysiology of PD and support interventions targeting thalamus as a potential therapeutic strategy. PMID- 26833138 TI - Influence of retinoic acid on human gingival epithelial barriers. AB - BACKGROUND AND OBJECTIVES: The gingival epithelium plays an important role in the protection of oral tissues from microbial challenge. Oral keratinocytes form a barrier and show various cellular contacts, including tight junctions (TJ). To analyse the barrier function in vitro the transepithelial electrical resistance (TER) is commonly used. Retinoic acid (RA) is an important signalling molecule in most tissues, including epithelial differentiation. RA signalling is mediated through three RA receptors. The aim of the study was to investigate the influence of RA on human gingival barriers in vitro. MATERIAL AND METHODS: Immortalized human gingival keratinocytes were seeded on culture plate inserts. The effect of RA with and without infection with Porphyromonas gingivalis W83 on the barrier was analysed by TER measurements. The expression of TJ proteins was investigated by western blot. RESULTS: During differentiation, mean TER increased from 16 (1 h), 43 (4 h) to 62 (6 h) Ohm * cm2 . Addition of 15 MUm RA increased TER by +19 after 1 h, +25 after 4 h and +16 Ohm * cm2 after 6 h. The pan-RA receptor inhibitor BMS 493 resulted in TER values comparable to the control. The mean established TER of the control was approximately 110 Ohm * cm2 . Addition of 15 MUm RA elevated TER to 127 Ohm * cm2 after 1 h, 150 Ohm * cm2 after 4 h and 189 Ohm * cm2 after 6 h (p <= 0.01). RA plus infection with P. gingivalis W83 further increased the TER increasing effect but could not prevent the destruction of TER induced by bacterial infection. The protein expression of the TJ proteins claudin 4 and occludin was enhanced while ZO-1 was downregulated after 1 h of RA incubation. CONCLUSION: RA provides barrier-positive elements to the gingival epithelial cell model that is accompanied by altered expression of TJ proteins. PMID- 26833137 TI - Central Gain Restores Auditory Processing following Near-Complete Cochlear Denervation. AB - Sensory organ damage induces a host of cellular and physiological changes in the periphery and the brain. Here, we show that some aspects of auditory processing recover after profound cochlear denervation due to a progressive, compensatory plasticity at higher stages of the central auditory pathway. Lesioning >95% of cochlear nerve afferent synapses, while sparing hair cells, in adult mice virtually eliminated the auditory brainstem response and acoustic startle reflex, yet tone detection behavior was nearly normal. As sound-evoked responses from the auditory nerve grew progressively weaker following denervation, sound-evoked activity in the cortex-and, to a lesser extent, the midbrain-rebounded or surpassed control levels. Increased central gain supported the recovery of rudimentary sound features encoded by firing rate, but not features encoded by precise spike timing such as modulated noise or speech. These findings underscore the importance of central plasticity in the perceptual sequelae of cochlear hearing impairment. PMID- 26833139 TI - A New Class of Safe Oligosaccharide Polymer Therapy To Modify the Mucus Barrier of Chronic Respiratory Disease. AB - The host- and bacteria-derived extracellular polysaccharide coating of the lung is a considerable challenge in chronic respiratory disease and is a powerful barrier to effective drug delivery. A low molecular weight 12-15-mer alginate oligosaccharide (OligoG CF-5/20), derived from plant biopolymers, was shown to modulate the polyanionic components of this coating. Molecular modeling and Fourier transform infrared spectroscopy demonstrated binding between OligoG CF 5/20 and respiratory mucins. Ex vivo studies showed binding induced alterations in mucin surface charge and porosity of the three-dimensional mucin networks in cystic fibrosis (CF) sputum. Human studies showed that OligoG CF-5/20 is safe for inhalation in CF patients with effective lung deposition and modifies the viscoelasticity of CF-sputum. OligoG CF-5/20 is the first inhaled polymer therapy, represents a novel mechanism of action and therapeutic approach for the treatment of chronic respiratory disease, and is currently in Phase IIb clinical trials for the treatment of CF. PMID- 26833140 TI - Evidence for the long-term maintenance of a rare self-incompatibility system in Oleaceae. AB - A rare homomorphic diallelic self-incompatibility (DSI) system discovered in Phillyrea angustifolia (family Oleaceae, subtribe Oleinae) can promote the transition from hermaphroditism to androdioecy. If widespread and stable in Oleaceae, DSI may explain the exceptionally high rate of androdioecious species reported in this plant family. Here, we set out to determine whether DSI occurs in another Oleaceae lineage. We tested for DSI in subtribe Fraxininae, a lineage that diverged from subtribe Oleinae c. 40 million yr ago. We explored the compatibility relationships in Fraxinus ornus using 81 hermaphrodites and 25 males from one natural stand and two naturalized populations using intra- and interspecific stigma tests performed on F. ornus and P. angustifolia testers. We uncovered a DSI system with hermaphrodites belonging to one of two self incompatibility (SI) groups and males compatible with both groups, making for a truly androdioecious reproductive system. The two human-founded populations contained only one of the two SI groups. Our results provide evidence for the evolutionary persistence of DSI. We discuss how its stability over time may have affected transitions to other sexual systems, such as dioecy. PMID- 26833141 TI - Whole genome sequencing reveals extensive community-level transmission of group A Streptococcus in remote communities. AB - Impetigo is common in remote Indigenous children of northern Australia, with the primary driver in this context being Streptococcus pyogenes [or group A Streptococcus (GAS)]. To reduce the high burden of impetigo, the transmission dynamics of GAS must be more clearly elucidated. We performed whole genome sequencing on 31 GAS isolates collected in a single community from children in 11 households with ?2 GAS-infected children. We aimed to determine whether transmission was occurring principally within households or across the community. The 31 isolates were represented by nine multilocus sequence types and isolates within each sequence type differed from one another by only 0-3 single nucleotide polymorphisms. There was evidence of extensive transmission both within households and across the community. Our findings suggest that strategies to reduce the burden of impetigo in this setting will need to extend beyond individual households, and incorporate multi-faceted, community-wide approaches. PMID- 26833142 TI - Effect of road transportation on the serum biochemical parameters of cynomolgus monkeys and beagle dogs. AB - To determine the effect of long-distance (approximately 600 km) road transportation on the blood biochemistry of laboratory animals, we investigated the changes in serum biochemical parameters in healthy cynomolgus monkeys and beagle dogs transported by truck from Osaka to Tsukuba, Japan. The concentrations of serum cortisol, total bilirubin and aspartate aminotransferase in monkeys increased during transportation. Serum cortisol and total bilirubin levels in dogs also increased during transportation, but serum triglyceride decreased. Serum parameter values in truck-transported monkeys and dogs returned to baseline levels within two weeks following arrival. Taken together, these results suggest that a two-week acclimation period is the minimum duration required for adaptation following road transportation. PMID- 26833143 TI - Potential benefits of physical activity during pregnancy for the reduction of gestational diabetes prevalence and oxidative stress. AB - Changes in quality of nutrition, habits, and physical activity in modern societies increase susceptibility to obesity, which can deleteriously affect pregnancy outcome. In particular, a sedentary lifestyle causes dysfunction in blood flow, which impacts the cardiovascular function of pregnant women. The main molecular mechanism responsible for this effect is the synthesis and bioavailability of nitric oxide, a phenomenon regulated by the antioxidant capacity of endothelial cells. These alterations affect the vascular health of the mother and vascular performance of the placenta, the key organ responsible for the healthy development of the fetus. In addition to the increases in systemic vascular resistance in the mother, placental oxidative stress also affects the feto-placental blood flow. These changes can be integrated into the proteomics and metabolomics of newborns. PMID- 26833144 TI - [Clinical efficacy of eculizumab as treatment of gemcitabine-induced thrombotic microangiopathy: A case report]. AB - INTRODUCTION: Gemcitabine-induced thrombotic microangiopathy is a rare event whose management is not yet consensual. The use of eculizumab could be of interest. CASE REPORT: A 68-year-old woman was treated by gemcitabine as adjuvant chemotherapy of a pancreatic adenocarcinoma. Two months later, the patient presented with mechanical hemolytic anemia, thrombocytopenia and high blood pressure that led to the diagnosis of thrombotic microangiopathy. Gemcitabine was stopped. Plasma exchange therapy was introduced since hematological and renal parameters had worsened. As clinical efficacy was insufficient, eculizumab was introduced at a dose of 900 mg per week 4 times, then 1200 mg every 2 weeks. Symptoms along with hematological and nephrological analysis were back to physiological standards after 7 intravenous injections. CONCLUSION: Eculizumab seems to be an effective treatment against gemcitabine-induced thrombotic microangiopathy in case of severe hematological and renal injuries associated with a lack of response to plasma exchange therapy. PMID- 26833145 TI - Management of giant cell arteritis: Recommendations of the French Study Group for Large Vessel Vasculitis (GEFA). AB - PURPOSE: Management of giant cell arteritis (GCA, Horton's disease) involves many uncertainties. This work was undertaken to establish French recommendations for GCA management. METHODS: Recommendations were developed by a multidisciplinary panel of 33 physicians, members of the French Study Group for Large Vessel Vasculitis (Groupe d'etude francais des arterites des gros vaisseaux [GEFA]). The topics to be addressed, selected from proposals by group members, were assigned to subgroups to summarize the available literature and draft recommendations. Following an iterative consensus-seeking process that yielded consensus recommendations, the degree of agreement among panel members was evaluated with a 5-point Likert scale. A recommendation was approved when >= 80% of the voters agreed or strongly agreed. RESULTS: The 15 retained topics resulted in 31 consensus recommendations focusing on GCA nomenclature and classification, the role of temporal artery biopsy and medical imaging in the diagnosis, indications and search modalities for involvement of the aorta and its branches, the glucocorticoid regimen to prescribe, treatment of complicated GCA, indications for use of immunosuppressants or targeted biologic therapies, adjunctive treatment measures, and management of relapse and recurrence. CONCLUSIONS: The recommendations, which will be updated regularly, are intended to guide and harmonize the standards of GCA management. PMID- 26833146 TI - [Multiple myeloma and venous thrombosis. Which thromboprophylaxis should be given?]. AB - Multiple myeloma is a malignant plasma cells dyscrasia that mainly affects patients older than 65 years. These patients are at a higher risk for venous thromboembolism (VTE) because of cancer status, intrinsic risk factors, and exposure to prothrombotic therapies. The risk for VTE appears higher during the first months of myeloma treatment and decreases over time. Exposure to immunomodulatory drugs (IMIDs) such as thalidomide or lenalidomide in association with high doses of dexamethasone or anthracyclin-based chemotherapy is associated with a four-fold increased risk for VTE. Low-dose aspirin, preventive-dose of low molecular weight heparin (LMWH) or vitamin K antagonists were tested for primary prevention of VTE in myeloma patients receiving chemotherapy. The International Myeloma Working Group (IMWG) suggests stratifying VTE risk to decide which patients should receive VTE prevention. Then, the IMWG suggests giving low-dose aspirin to low VTE risk patients and LMWH or vitamin K antagonists to patients at high risk for VTE. For daily practice, it seems reasonable to start preventive doses of LMWH for 3 to 6 months in ambulatory myeloma patients receiving combined therapy with IMID and in all myeloma patients admitted to hospital. PMID- 26833147 TI - Role of the Stringent Stress Response in the Antibiotic Resistance Phenotype of Methicillin-Resistant Staphylococcus aureus. AB - Resistance to beta-lactam antibiotics in methicillin-resistantStaphylococcus aureus(MRSA) requires the presence of an acquired genetic determinant,mecAormecC, which encode penicillin-binding protein PBP2A or PBP2A', respectively. Although all MRSA strains share a mechanism of resistance, the phenotypic expression of beta-lactam resistance shows considerable strain-to-strain variation. The stringent stress response, a stress response that results from nutrient limitation, was shown to play a key role in determining the resistance level of an MRSA strain. In the present study, we validated the impact of the stringent stress response on transcription and translation ofmecAin the MRSA clinical isolate strain N315, which also carries known regulatory genes (mecI/mecR1/mecR2andblaI/blaR1) formecAtranscription. We showed that the impact of the stringent stress response on the resistance level may be restricted to beta-lactam resistance based on a "foreign" determinant such asmecA, as opposed to resistance based on mutations in the nativeS. aureusdeterminantpbpB(encoding PBP2). Our observations demonstrate that high-level resistance mediated by the stringent stress response follows the current model of beta-lactam resistance in which the native PBP2 protein is also essential for expression of the resistance phenotype. We also show that theStaphylococcus sciuri pbpDgene (also calledmecAI), the putative evolutionary precursor ofmecA, confers oxacillin resistance in anS. aureusstrain, generating a heterogeneous phenotype that can be converted to high and homogenous resistance by induction of the stringent stress response in the bacteria. PMID- 26833148 TI - The Recombinant Bacteriophage Endolysin HY-133 Exhibits In Vitro Activity against Different African Clonal Lineages of the Staphylococcus aureus Complex, Including Staphylococcus schweitzeri. AB - HY-133 is a recombinant bacteriophage endolysin with bactericidal activity againstStaphylococcus aureus Here, HY-133 showedin vitroactivity against major African methicillin-susceptible and methicillin-resistantS. aureuslineages and ceftaroline/ceftobiprole- and borderline oxacillin-resistant isolates. HY-133 was also active againstStaphylococcus schweitzeri, a recently described species of theS. aureuscomplex. The activity of HY-133 on the tested isolates (MIC50, 0.25 MUg/ml; MIC90, 0.5 MUg/ml; range, 0.125 to 0.5 MUg/ml) was independent of the species and strain background or antibiotic resistance. PMID- 26833149 TI - Whole-Genome Sequence of a blaOXA-48-Harboring Raoultella ornithinolytica Clinical Isolate from Lebanon. AB - We analyzed the whole-genome sequence of ablaOXA-48-harboringRaoultella ornithinolyticaclinical isolate from a patient in Lebanon. The size of theRaoultella ornithinolyticaCMUL058 genome was 5,622,862 bp, with a G+C content of 55.7%. We deciphered all the molecular mechanisms of antibiotic resistance, and we compared our genome to other availableR. ornithinolyticagenomes in GenBank. The resistome consisted of 9 antibiotic resistance genes, including a plasmidicblaOXA-48gene whose genetic organization is also described. PMID- 26833150 TI - Untargeted Metabolomics To Ascertain Antibiotic Modes of Action. AB - Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also collect data on off-target effects and drug modifications. Here, we present data from an untargeted liquid chromatography-mass spectrometry approach to identify the modes of action of eight compounds: 1-[3-fluoro-4-(5 methyl-2,4-dioxo-pyrimidin-1-yl)phenyl]-3-[2-(trifluoromethyl)phenyl]urea (AZ1), 2-(cyclobutylmethoxy)-5'-deoxyadenosine, triclosan, fosmidomycin, CHIR-090, carbonyl cyanidem-chlorophenylhydrazone (CCCP), 5-chloro-2-(methylsulfonyl)-N (1,3-thiazol-2-yl)-4-pyrimidinecarboxamide (AZ7), and ceftazidime. Data analysts were blind to the compound identities but managed to identify the target as thymidylate kinase for AZ1, isoprenoid biosynthesis for fosmidomycin, acyl transferase for CHIR-090, and DNA metabolism for 2-(cyclobutylmethoxy)-5' deoxyadenosine. Changes to cell wall metabolites were seen in ceftazidime treatments, although other changes, presumably relating to off-target effects, dominated spectral outputs in the untargeted approach. Drugs which do not work through metabolic pathways, such as the proton carrier CCCP, have no discernible impact on the metabolome. The untargeted metabolomics approach also revealed modifications to two compounds, namely, fosmidomycin and AZ7. An untreated control was also analyzed, and changes to the metabolome were seen over 4 h, highlighting the necessity for careful controls in these types of studies. Metabolomics is a useful tool in the analysis of drug modes of action and can complement other technologies already in use. PMID- 26833151 TI - 5-Azacytidine Enhances the Mutagenesis of HIV-1 by Reduction to 5-Aza-2' Deoxycytidine. AB - 5-Azacytidine (5-aza-C) is a ribonucleoside analog that induces the lethal mutagenesis of human immunodeficiency virus type 1 (HIV-1) by causing predominantly G-to-C transversions during reverse transcription. 5-Aza-C could potentially act primarily as a ribonucleotide (5-aza-CTP) or as a deoxyribonucleotide (5-aza-2'-deoxycytidine triphosphate [5-aza-dCTP]) during reverse transcription. In order to determine the primary form of 5-aza-C that is active against HIV-1, Illumina sequencing was performed using proviral DNA from cells treated with 5-aza-C or 5-aza-dC. 5-Aza-C and 5-aza-dC were found to induce highly similar patterns of mutation in HIV-1 in terms of the types of mutations observed, the magnitudes of effects, and the distributions of mutations at individual sequence positions. Further, 5-aza-dCTP was detected by liquid chromatography-tandem mass spectrometry in cells treated with 5-aza-C, demonstrating that 5-aza-C was a substrate for ribonucleotide reductase. Notably, levels of 5-aza-dCTP were similar in cells treated with equivalent effective concentrations of 5-aza-C or 5-aza-dC. Lastly, HIV-1 reverse transcriptase was found to incorporate 5-aza-CTPin vitroat least 10,000-fold less efficiently than 5-aza-dCTP. Taken together, these data support the model that 5-aza-C enhances the mutagenesis of HIV-1 primarily after reduction to 5-aza-dC, which can then be incorporated during reverse transcription and lead to G-to-C hypermutation. These findings may have important implications for the design of new ribonucleoside analogs directed against retroviruses. PMID- 26833152 TI - Doravirine Suppresses Common Nonnucleoside Reverse Transcriptase Inhibitor Associated Mutants at Clinically Relevant Concentrations. AB - Doravirine (DOR), which is currently in a phase 3 clinical trial, is a novel human immunodeficiency type 1 virus (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI). DOR exhibits potent antiviral activity against wild-type virus and K103N, Y181C, and K103N/Y181C mutant viruses, with 50% inhibitory concentrations (IC50s) of 12, 21, 31, and 33 nM, respectively, when measured in 100% normal human serum (NHS). To assess the potential for DOR to suppress NNRTI associated and rilpivirine (RPV)-specific mutants at concentrations achieved in the clinic setting, inhibitory quotients (IQs) were calculated by determining the ratio of the clinical trough concentration over the antiviral IC50for each virus with DOR and RPV and efavirenz (EFV). DOR displayed IQs of 39, 27, and 25 against the K103N, Y181C, and K103N/Y181C mutants, respectively. In contrast, RPV exhibited IQs of 4.6, 1.4, and 0.8, and EFV showed IQs of 2.5, 60, and 1.9 against these viruses, respectively. DOR also displayed higher IQs than those of RPV and EFV against other prevalent NNRTI-associated mutants, with the exception of Y188L. Both DOR and EFV exhibited higher IQs than RPV when analyzed with RPV associated mutants. Resistance selections were conducted with K103N, Y181C, G190A, and K103N/Y181C mutants at clinically relevant concentrations of DOR, RPV, and EFV. No viral breakthrough was observed with DOR, whereas breakthrough viruses were readily detected with RPV and EFV against Y181C and K103N viruses, respectively. These data suggest that DOR should impose a higher barrier to the development of resistance than RPV and EFV at the concentrations achieved in the clinic setting. PMID- 26833153 TI - OligoG CF-5/20 Disruption of Mucoid Pseudomonas aeruginosa Biofilm in a Murine Lung Infection Model. AB - Biofilm growth is a universal survival strategy for bacteria, providing an effective and resilient approach for survival in an otherwise hostile environment. In the context of an infection, a biofilm provides resistance and tolerance to host immune defenses and antibiotics, allowing the biofilm population to survive and thrive under conditions that would destroy their planktonic counterparts. Therefore, the disruption of the biofilm is a key step in eradicating persistent bacterial infections, as seen in many types of chronic disease. In these studies, we used both in vitro minimum biofilm eradication concentration (MBEC) assays and an in vivo model of chronic biofilm infection to demonstrate the biofilm-disrupting effects of an alginate oligomer, OligoG CF 5/20. Biofilm infections were established in mice by tracheal instillation of a mucoid clinical isolate of Pseudomonas aeruginosa embedded in alginate polymer beads. The disruption of the biofilm by OligoG CF-5/20 was observed in a dose dependent manner over 24 h, with up to a 2.5-log reduction in CFU in the infected mouse lungs. Furthermore, in vitro assays showed that 5% OligoG CF-5/20 significantly reduced the MBEC for colistin from 512 MUg/ml to 4 MUg/ml after 8 h. These findings support the potential for OligoG CF-5/20 as a biofilm disruption agent which may have clinical value in reducing the microbial burden in chronic biofilm infections. PMID- 26833154 TI - Bidirectional Transfer of Raltegravir in an Ex Vivo Human Cotyledon Perfusion Model. AB - Placental transfer of the HIV integrase inhibitor raltegravir (RLT) was investigated in term human cotyledons in the maternal-to-fetal (n = 3) and fetal to-maternal (n = 6) directions. In the maternal-to-fetal direction, the mean +/- standard deviation (SD) fetal transfer rate (FTR) was 9.1% +/- 1.4%, and the mean +/- SD clearance index (IC), i.e., RLT FTR/antipyrine FTR, was 0.28 +/- 0.05. In the fetal-to-maternal direction, the mean +/- SD CI was 0.31 +/- 0.09. Placental transfer of RLT was high in both directions. PMID- 26833155 TI - Amino Acid Substitutions Account for Most MexS Alterations in Clinical nfxC Mutants of Pseudomonas aeruginosa. AB - Multidrug-resistant mutants ofPseudomonas aeruginosathat overproduce the active efflux system MexEF-OprN (callednfxCmutants) have rarely been characterized in the hospital setting. Screening of 221 clinical strains exhibiting a reduced susceptibility to ciprofloxacin (a substrate of MexEF-OprN) and imipenem (a substrate of the negatively coregulated porin OprD) led to the identification of 43 (19.5%)nfxCmutants. Subsequent analysis of 22 nonredundant mutants showed that, in contrast to theirin vitro-selected counterparts, only 3 of them (13.6%) harbored a disruptedmexSgene, which codes for the oxidoreductase MexS, whose inactivation is known to activate themexEF-oprNoperon through a LysR-type regulator, MexT. Nine (40.9%) of the clinicalnfxCmutants contained single amino acid mutations in MexS, and these were associated with moderate effects on resistance and virulence factor production in 8/9 strains. Finally, the remaining 10 (45.5%)nfxCmutants did not display mutations in any of the regulators known to controlmexEF-oprNexpression (themexS,mexT,mvaT, andampRgenes), confirming that other loci are responsible for pump upregulation in patients. Collectively, these data demonstrate thatnfxCmutants are probably more frequent in the hospital than previously thought and have genetic and phenotypic features somewhat different from those ofin vitro-selected mutants. PMID- 26833156 TI - Cell Wall Changes in Amphotericin B-Resistant Strains from Candida tropicalis and Relationship with the Immune Responses Elicited by the Host. AB - We have morphologically characterizedCandida tropicalisisolates resistant to amphotericin B (AmB). These isolates present an enlarged cell wall compared to isolates of regular susceptibility. This correlated with higher levels of beta 1,3-glucan in the cell wall but not with detectable changes in chitin content. In line with this, AmB-resistant strains showed reduced susceptibility to Congo red. Moreover, mitogen-activated protein kinases (MAPKs) involved in cell integrity were already activated during regular growth in these strains. Finally, we investigated the response elicited by human blood cells and found that AmB resistant strains induced a stronger proinflammatory response than susceptible strains. In agreement, AmB-resistant strains also induced stronger melanization ofGalleria mellonellalarvae, indicating that the effect of alterations of the cell wall on the immune response is conserved in different types of hosts. Our results suggest that resistance to AmB is associated with pleiotropic mechanisms that might have important consequences, not only for the efficacy of the treatment but also for the immune response elicited by the host. PMID- 26833157 TI - A High-Affinity Native Human Antibody Disrupts Biofilm from Staphylococcus aureus Bacteria and Potentiates Antibiotic Efficacy in a Mouse Implant Infection Model. AB - Many serious bacterial infections are difficult to treat due to biofilm formation, which provides physical protection and induces a sessile phenotype refractory to antibiotic treatment compared to the planktonic state. A key structural component of biofilm is extracellular DNA, which is held in place by secreted bacterial proteins from the DNABII family: integration host factor (IHF) and histone-like (HU) proteins. A native human monoclonal antibody, TRL1068, has been discovered using single B-lymphocyte screening technology. It has low picomolar affinity against DNABII homologs from important Gram-positive and Gram negative bacterial pathogens. The disruption of established biofilm was observedin vitroat an antibody concentration of 1.2 MUg/ml over 12 h. The effect of TRL1068in vivowas evaluated in a murine tissue cage infection model in which a biofilm is formed by infection with methicillin-resistantStaphylococcus aureus(MRSA; ATCC 43300). Treatment of the established biofilm by combination therapy of TRL1068 (15 mg/kg of body weight, intraperitoneal [i.p.] administration) with daptomycin (50 mg/kg, i.p.) significantly reduced adherent bacterial count compared to that after daptomycin treatment alone, accompanied by significant reduction in planktonic bacterial numbers. The quantification of TRL1068 in sample matrices showed substantial penetration of TRL1068 from serum into the cage interior. TRL1068 is a clinical candidate for combination treatment with standard-of-care antibiotics to overcome the drug-refractory state associated with biofilm formation, with potential utility for a broad spectrum of difficult-to-treat bacterial infections. PMID- 26833158 TI - Pharmacodynamics of Voriconazole in Children: Further Steps along the Path to True Individualized Therapy. AB - Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model that links the pharmacokinetics of voriconazole with the galactomannan readout in children. Twelve children receiving voriconazole for treatment of proven, probable, and possible invasive fungal infections were studied. A previously published population PK model was used as the Bayesian prior. The PK-PD model was used to estimate the average area under the concentration-time curve (AUC) in each patient and the resultant galactomannan-time profile. The relationship between the ratio of the AUC to the concentration of voriconazole that induced half maximal killing (AUC/EC50) and the terminal galactomannan level was determined. The voriconazole concentration-time and galactomannan-time profiles were both highly variable. Despite this variability, the fit of the PK-PD model was good, enabling both the pharmacokinetics and pharmacodynamics to be described in individual children. (AUC/EC50)/15.4 predicted terminal galactomannan (P= 0.003), and a ratio of >6 suggested a lower terminal galactomannan level (P= 0.07). The construction of linked PK-PD models is the first step in developing control software that enables not only individualized voriconazole dosages but also individualized concentration targets to achieve suppression of galactomannan levels in a timely and optimally precise manner. Controlling galactomannan levels is a first critical step to maximizing clinical response and survival. PMID- 26833160 TI - Evaluation of the Efficacy of ME1111 in the Topical Treatment of Dermatophytosis in a Guinea Pig Model. AB - The treatment of dermatophytoses, including onychomycosis, has come a long way over the past few decades with the introduction of oral antifungals (e.g., terbinafine and itraconazole). However, with these advancements in oral therapies come several undesirable effects, such as kidney and liver toxicity, along with drug-drug interactions. Consequently, there is a need for new topical agents that are effective against dermatophytosis. ME1111 is a topical antifungal under development. In this study, thein vivoefficacy of ME1111 was compared to that of ciclopirox in the topical treatment of dermatophytosis caused byTrichophyton mentagrophytesusing a guinea pig model. Animals were treated with the topical antifungals starting at 3 days postinfection, with each agent being applied once daily for seven consecutive days. After the treatment period, the clinical and mycological efficacies were evaluated. The data showed that both antifungals demonstrated significant clinical and mycological efficacies; however, ME1111 showed clinical efficacy superior to that of ciclopirox (46.9% and 25.0%, respectively, with aPvalue of <0.001). The potent efficacy of ME1111 could be attributed to its properties, such as low keratin binding. PMID- 26833159 TI - Oritavancin Combinations with beta-Lactams against Multidrug-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci. AB - Oritavancin possesses activity against vancomycin-resistant enterococci (VRE) and methicillin-resistantStaphylococcus aureus(MRSA).In vitrodata suggest synergy between beta-lactams (BLs) and vancomycin or daptomycin, agents similar to oritavancin. We evaluated the activities of BLs combined with oritavancin against MRSA and VRE. Oritavancin MICs were determined for 30 strains, 5 each of MRSA, daptomycin-nonsusceptible (DNS) MRSA, vancomycin-intermediate MRSA (VISA), heteroresistant VISA (hVISA), vancomycin-resistantEnterococcus faecalis, and vancomycin-resistantEnterococcus faecium Oritavancin MICs were determined in the presence of subinhibitory concentrations of BLs. Oritavancin combined with ceftaroline, cefazolin, or nafcillin was evaluated for lethal synergy against MRSA, and oritavancin combined with ceftaroline, ampicillin, or ertapenem was evaluated for lethal synergy against VRE in 24-h time-kill assays. Oritavancin at 0.5* the MIC was combined with BLs at 0.5* the MIC or the biological free peak concentration, whichever one was lower. Synergy was defined as a >=2-log10-CFU/ml difference between the killing achieved with the combination and that achieved with the most active single agent at 24 h. Oritavancin MICs were <=0.125 MUg/ml for all MRSA isolates except three VISA isolates with MICs of 0.25 MUg/ml. Oritavancin MICs for VRE ranged from 0.03 to 0.125 MUg/ml. Oritavancin in combination with ceftaroline was synergistic against all MRSA phenotypes and statistically superior to all other combinations against DNS MRSA, hVISA, and MRSA isolates (P< 0.02). Oritavancin in combination with cefazolin and oritavancin in combination with nafcillin were also synergistic against all MRSA strains. Synergy between oritavancin and all BLs was revealed against VRE strain 8019, while synergy between oritavancin and ampicillin or ertapenem but not ceftaroline was demonstrated against VRE strain R7164. The data support the potential use of oritavancin in combination with BLs, especially oritavancin in combination with ceftaroline, for the treatment of infections caused by MRSA. The data from the present study are not as strong for oritavancin in combination with BLs for VRE. Further study of both MRSA and VRE in more complex models is warranted. PMID- 26833161 TI - Population Structure Analysis of Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates from Brazil Reveals Predominance of Clonal Complexes 1, 15, and 79. AB - The population structure of 71 carbapenem-resistantAcinetobacter baumanniiclinical isolates from several hospitals in Brazil was investigated by ApaI pulsed-field gel electrophoresis,blaOXA-51-like subtyping, and multilocus sequence typing (Institute Pasteur scheme). In addition to the predominance of strains carryingblaOXA-23, we detected the presence ofblaOXA-72andblaOXA-231 We observed a predominance of clonal complex 1 (CC1), CC15, and CC79 and representative strains of the worldwide-disseminated international clone I. PMID- 26833162 TI - Contribution of Gag and Protease to HIV-1 Phenotypic Drug Resistance in Pediatric Patients Failing Protease Inhibitor-Based Therapy. AB - Protease inhibitors (PIs) are used as a first-line regimen in HIV-1-infected children. Here we investigated the phenotypic consequences of amino acid changes in Gag and protease on lopinavir (LPV) and ritonavir (RTV) susceptibility among pediatric patients failing PI therapy. The Gag-protease from isolates from 20 HIV 1 subtype C-infected pediatric patients failing an LPV and/or RTV-based regimen was phenotyped using a nonreplicativein vitroassay. Changes in sensitivity to LPV and RTV relative to that of the matched baseline (pretherapy) sample were calculated. Gag and protease amino acid substitutions associated with PI failure were created in a reference clone by site-directed mutagenesis and assessed. Predicted phenotypes were determined using the Stanford drug resistance algorithm. Phenotypic resistance or reduced susceptibility to RTV and/or LPV was observed in isolates from 10 (50%) patients, all of whom had been treated with RTV. In most cases, this was associated with protease resistance mutations, but substitutions at Gag cleavage and noncleavage sites were also detected. Gag amino acid substitutions were also found in isolates from three patients with reduced drug susceptibilities who had wild-type protease. Site-directed mutagenesis confirmed that some amino acid changes in Gag contributed to PI resistance but only in the presence of major protease resistance-associated substitutions. The isolates from all patients who received LPV exclusively were phenotypically susceptible. Baseline isolates from the 20 patients showed a large (47-fold) range in the 50% effective concentration of LPV, which accounted for most of the discordance seen between the experimentally determined and the predicted phenotypes. Overall, the inclusion of thegaggene and the use of matched baseline samples provided a more comprehensive assessment of the effect of PI-induced amino acid changes on PI resistance. The lack of phenotypic resistance to LPV supports the continued use of this drug in pediatric patients. PMID- 26833163 TI - Global Urine Metabolomics in Patients Treated with First-Line Tuberculosis Drugs and Identification of a Novel Metabolite of Ethambutol. AB - Population level variation of drug metabolism phenotype (DMP) has great implications in treatment outcome, drug-related side effects, and resistance development. In this study, we used a gas chromatography-time of flight-mass spectrometry (GC-TOF-MS)-based untargeted urine metabolomics approach to understand the DMP of a tuberculosis (TB) patient cohort (n= 20) from Tripura, a state in the northeastern part of India. Urine samples collected at different postdose time points (2 h, 6 h, 12 h, 24 h, 36 h, and 48 h) from these newly diagnosed TB patients receiving first-line anti-TB drugs were analyzed, and we have successfully detected three of the four first-line drugs,viz, isoniazid (INH), ethambutol (ETB), and pyrazinamide (PZA). The majority of their known metabolites, acetyl-isoniazid (AcINH), isonicotinic acid (INA), isonicotinuric acid (INTA), 2,2'-(ethylenediimino)-dibutyric acid (EDBA), 5-hydroxypyrazinamide (5OH-PZA), pyrazinoic acid (POA), and 5-hydroxypyrazinoic acid (5OH-POA), were also detected. Analyzing the variation in abundances of drugs and their known metabolites and calculating the metabolic ratios in these samples, we offer comprehensive DMP information on this small patient cohort that represents Tripura, India. The majority (75%) of these patients are found to be slow acetylators of INH. The average metabolic ratios of POA/PZA and 5OH-POA/POA are 3.16 +/- 3.03 and 6.09 +/- 6.15, respectively. Employing correlation analysis of the metabolomics metadata and a manual prediction of drug catabolism, we have proposed 2-aminobutyric acid (AABA) as a novel metabolite of ETB. These observations indicate the usefulness of GC-MS-based metabolomics to characterize the DMP at a population level and also to identify novel drug metabolites. PMID- 26833164 TI - Combination of Amphotericin B and Flucytosine against Neurotropic Species of Melanized Fungi Causing Primary Cerebral Phaeohyphomycosis. AB - Primary central nervous system phaeohyphomycosis is a fatal fungal infection due mainly to the neurotropic melanized fungiCladophialophora bantiana,Rhinocladiella mackenziei, andExophiala dermatitidis.Despite the combination of surgery with antifungal treatment, the prognosis continues to be poor, with mortality rates ranging from 50 to 70%. Therefore, a search for a more-appropriate therapeutic approach is urgently needed. Ourin vitrostudies showed that with the combination of amphotericin B and flucytosine against these species, the median fractional inhibitory concentration (FIC) indices for strains ranged from 0.25 to 0.38, indicating synergy. By use of Bliss independence analysis, a significant degree of synergy was confirmed for all strains, with the sum DeltaE ranging from 90.2 to 698.61%. No antagonism was observed. These results indicate that amphotericin B, in combination with flucytosine, may have a role in the treatment of primary cerebral infections caused by melanized fungi belonging to the orderChaetothyriales Furtherin vivostudies and clinical investigations to elucidate and confirm these observations are warranted. PMID- 26833165 TI - Linezolid Surveillance Results for the United States (LEADER Surveillance Program 2014). AB - Thelinezolidexperience andaccuratedetermination ofresistance (LEADER) surveillance program has monitored linezolid activity, spectrum, and resistance since 2004. In 2014, a total of 6,865 Gram-positive pathogens from 60 medical centers from 36 states were submitted. The organism groups evaluated wereStaphylococcus aureus(3,106), coagulase-negative staphylococci (CoNS; 797), enterococci (855),Streptococcus pneumoniae(874), viridans group streptococci (359), and beta-hemolytic streptococci (874). Susceptibility testing was performed by reference broth microdilution at the monitoring laboratory. Linezolid-resistant isolates were confirmed by repeat testing. PCR and sequencing were performed to detect mutations in 23S rRNA, L3, L4, and L22 proteins and acquired genes (cfrandoptrA). The MIC50/90forStaphylococcus aureuswas 1/1 MUg/ml, with 47.2% of isolates being methicillin-resistantStaphylococcus aureus Linezolid was active against allStreptococcus pneumoniaestrains and beta-hemolytic streptococci with a MIC50/90of 1/1 MUg/ml and against viridans group streptococci with a MIC50/90of 0.5/1 MUg/ml. Among the linezolid-nonsusceptible MRSA strains, one strain harboredcfronly (MIC, 4 MUg/ml), one harbored G2576T (MIC, 8 MUg/ml), and one containedcfrand G2576T with L3 changes (MIC, >=8 MUg/ml). Among CoNS, 0.75% (six isolates) of all strains demonstrated linezolid MIC results of >=4 MUg/ml. Five of these were identified asStaphylococcus epidermidis, four of which containedcfrin addition to the presence of mutations in the ribosomal proteins L3 and L4, alone or in combination with 23S rRNA (G2576T) mutations. Six enterococci (0.7%) were linezolid nonsusceptible (>=4 MUg/ml; five with G2576T mutations, including one with an additionalcfrgene, and one strain withoptrAonly). Linezolid demonstrated excellent activity and a sustained susceptibility rate of 99.78% overall. PMID- 26833166 TI - Prediction of Fluoroquinolone Resistance in Gram-Negative Bacteria Causing Bloodstream Infections. AB - Increasing rates of fluoroquinolone resistance (FQ-R) have limited empirical treatment options for Gram-negative infections, particularly in patients with severe beta-lactam allergy. This case-control study aims to develop a clinical risk score to predict the probability of FQ-R in Gram-negative bloodstream isolates. Adult patients with Gram-negative bloodstream infections (BSI) hospitalized at Palmetto Health System in Columbia, South Carolina, from 2010 to 2013 were identified. Multivariate logistic regression was used to identify independent risk factors for FQ-R. Point allocation in the fluoroquinolone resistance score (FQRS) was based on regression coefficients. Model discrimination was assessed by the area under receiver operating characteristic curve (AUC). Among 824 patients with Gram-negative BSI, 143 (17%) had BSI due to fluoroquinolone-nonsusceptible Gram-negative bacilli. Independent risk factors for FQ-R and point allocation in FQRS included male sex (adjusted odds ratio [aOR], 1.97; 95% confidence intervals [CI], 1.36 to 2.98; 1 point), diabetes mellitus (aOR, 1.54; 95% CI, 1.03 to 2.28; 1 point), residence at a skilled nursing facility (aOR, 2.28; 95% CI, 1.42 to 3.63; 2 points), outpatient procedure within 30 days (aOR, 3.68; 95% CI, 1.96 to 6.78; 3 points), prior fluoroquinolone use within 90 days (aOR, 7.87; 95% CI, 4.53 to 13.74; 5 points), or prior fluoroquinolone use within 91 to 180 days of BSI (aOR, 2.77; 95% CI, 1.17 to 6.16; 3 points). The AUC for both final logistic regression and FQRS models was 0.73. Patients with an FQRS of 0, 3, 5, or 8 had predicted probabilities of FQ-R of 6%, 22%, 39%, or 69%, respectively. The estimation of patient-specific risk of antimicrobial resistance using FQRS may improve empirical antimicrobial therapy and fluoroquinolone utilization in Gram-negative BSI. PMID- 26833168 TI - Common bleeding disorders affecting individuals with Hereditary Hemorrhagic Telangiectasia. AB - PURPOSE: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disorder affecting vasculature in different organ systems; seen at a rate of approximately 1:5000 in North America. Complications, with significant increases in health service utilization, arise from bleeding and shunts, and are particularly problematic in the lung and liver. Although these patients tend to chronically bleed from the GI tract and nasal cavities, a single bleed from arterio-venous malformations in the lungs or brain can have serious health implications and may be fatal. Bleeding due to vascular wall fragility in HHT patients can be further complicated with a concomitant bleeding disorder. METHODS: The proportion of adult patients seen in the Edmonton HHT center with a concomitant bleeding disorder, as assessed by blood test results for Factor VIII and related factors (Ristocetin Cofactor), Factor IX and Factor XI, was determined in a retrospective, single centre study. RESULTS: Of 77 individuals with HHT, four had below normal values of von Willebrand Factor, Ristocetin Cofactor or Factor VIII. Two patients had laboratory parameters diagnostic of a bleeding disorder, accounting for 2.6% of confirmed HHT subjects. These results indicate that establishing screening for bleeding disorders in HHT centers is important in managing bleeding symptomatology. CONCLUSIONS: In individuals with HHT, the presence of a second bleeding disorder can have significant clinical implications on patient management and health care utilizations. This paper highlights areas that need to be reviewed with respect to best practice protocols for the management of HHT patients. PMID- 26833167 TI - A Multicenter Study in Mexico Finds Acinetobacter baumannii Clinical Isolates Belonging to Clonal Complexes 636B (113B) and 92B Harboring OXA-72, OXA-239, and OXA-469. PMID- 26833169 TI - Reduction of Acute Lung Injury by Administration of Spironolactone After Intestinal Ischemia and Reperfusion in Rats. AB - PURPOSE: Multiple organ failure, including acute lung injury, is a common complication of intestinal ischemia and reperfusion (I/R) injury and contributes to its high mortality rate. Activated polymorphonuclear neutrophils and reactive oxygen species contribute to the lung injury caused by intestinal I/R. Mineralocorticoid receptor antagonist spironolactone has a protective effect against I/R injury in animal models of retina, kidney, heart, and brain. The aim of the present study is to investigate the effect of aldosterone receptor blocker spironolactone on lung injury induced by intestinal I/R. METHODS: Wistar albino rats were divided into four groups: (1) sham control; (2) intestinal I/R (30 min of ischemia by superior mesenteric artery occlusion followed by 3 h of reperfusion); (3) spironolactone pretreatment (20 mg/kg) + I/R; and, (4) spironolactone pretreatment without I/R. Spironolactone was given orally 3 days prior to intestinal I/R. A marker for lipid peroxidation (malondialdehyde; MDA), an indicator or oxidation state (reduced glutathione; GSH), an index of polymorphonuclear neutrophil sequestration (myeloperoxidase; MPO), inducible nitric oxide synthase (iNOS) immunoreactivity, and the histopathology of the lung tissue were analyzed. RESULTS: Spironolactone pretreatment markedly reduced intestinal I/R-induced lung injury as indicated by histology and MDA and MPO levels. Moreover, the pretreatment decreased the iNOS immunoreactivity. CONCLUSION: The present study strongly suggests that spironolactone pretreatment decreased neutrophil infiltration, iNOS induction, oxidative stress, and histopathological injury in an experimental model of intestinal I/R induced-lung injury of rats. PMID- 26833170 TI - Comparing treatment outcomes of fractional flow reserve-guided and angiography guided percutaneous coronary intervention in patients with multi-vessel coronary artery diseases: a systematic review and meta-analysis. AB - PURPOSE: Fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) is used to assess the need for angioplasty in vessels with intermediate blockages. The treatment outcomes of FFR-guided vs. conventional angiography guided PCI were evaluated in patients with multi-vessel coronary artery disease (CAD). METHODS: Prospective and retrospective studies comparing FFR-guided vs. angiography-guided PCI in patients with multi-vessel CAD were identified from medical databases by two independent reviewers using the terms "percutaneous coronary intervention, fractional flow reserve, angiography, coronary heart disease, major adverse cardiac events (MACE) and myocardial infarction". The primary outcome was the number of stents placed, and the secondary outcomes were procedure time, mortality, myocardial infarction (MI) and MACE rates. RESULTS: Seven studies (three retrospective and four prospective), which included 49,517 patients, were included in this review. A total of 4,755 patients underwent FFR, while 44,697 received angiography-guided PCI. The mean patient age ranged from 58 to 71.7 years. The average number of stents used in FFR patients ranged from 0.3 1.9, and in angiography-guided PCI patients ranged from 0.7-2.7. Analysis indicated there was a greater number of stents placed in the angiography-guided group compared with the FFR group (pooled difference in means: -0.64, 95% confidence interval [CI]: -0.81 to -0.47, P < 0.001). There were no differences in the secondary outcomes between the two groups. CONCLUSIONS: Both procedures produce similar clinical outcomes, but the fewer number of stents used with FFR may have clinical as was as cost implications. PMID- 26833171 TI - Li-Fraumeni Syndrome and p53 in 2015: Celebrating their Silver Anniversary. AB - In a typical morning in the Cancer Genetics Clinic at The Hospital for Sick Children in Toronto, the following array of patients and families might be seen: a family of three children, all harbouring a mutation of the succinyl dehydrogenase C gene inherited from their father who had had extensive surgery several years ago for a secreting paraganglioma; three families with Li-Fraumeni syndrome, each with at least one child harbouring a TP53 gene mutation conferring a lifetime risk of cancer approaching 100% and currently undergoing surveillance for early tumour detection; two children with Li-Fraumeni syndrome undergoing treatment for cancer - one having had three cancer diagnoses before 19 months of age and the other just completing therapy for metastatic adrenocortical carcinoma at age 3; two children with von Hippel-Lindau disease being monitored for persistent pancreatic neuroendocrine tumors and cerebellar hemangioblastomas, respectively; and one child with Beckwith-Wiedeman syndrome and Wilms tumor and another child completing therapy for a pleuropulmonary blastoma (PPB). PMID- 26833172 TI - Protective effects of molsidomine against doxorubicin-induced renal damage in rats. AB - PURPOSE: The purpose of this study was to investigate the therapeutic and protective effects of molsidomine (MLS) against doxorubicin (DOX)-induced renal damage in rats. METHODS: Forty rats were randomly divided into five groups (control, MLS, DOX, DOX+MLS and MLS+DOX groups). Thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), nitric oxide (NO) and glutathione peroxidase (GPx) levels were determined from kidney tissues and blood urea nitrogen (BUN), creatinine (Cr) and albumin (Alb) levels also determined. RESULTS: DOX treatment caused a significant increase in TBARS levels and a significant decrease in the GSH and CAT levels compared with the control group. In comparison, MLS administration before DOX injection caused a significant decrease in TBARS levels and also increases in GSH and CAT levels, whereas treatment of MLS after DOX injection did not show any beneficial effect on these parameters. All groups showed a significant increase in NO levels compared to the control group. There were no significant differences among the all groups for BUN and Cr levels. Serum level of Alb decreased in the DOX-treated groups when compared with control and MLS groups. The histopathological findings were in accordance with the biochemical results. MLS treatment reversed the DOX-induced kidney damage in group 4. MLS treatment before DOX injection exerted a protective effect against DOX-induced kidney damage. CONCLUSIONS: MLS shows promise as a possible therapeutic intervention for the prevention of kidney injury associated with DOX treatment. Additional studies are warranted. PMID- 26833173 TI - Women service members, veterans, and their families: What we know now. AB - The purpose of this paper is to highlight what we know now about female service members, veterans, and their families. The experiences of U.S. female service members and veterans are more complex than previous eras and significant demographic changes have taken place. U.S. female veterans are more likely to be younger, come from ethnic and racial minority groups, have children, and combat exposure. U.S. female service members report high rates of sexual violence and they are more vulnerable to homelessness and unemployment when compared to previous female military cohorts. U.S. female service members and veterans are also at higher risk for significant mental and health issues. Children and adolescents of women service members and veterans may also carry a heavy burden as a result of lengthy deployments. A majority of female service members and veterans will utilize community based healthcare and social services, therefore, it is essential that all healthcare providers understand the unique needs of this cohort of women. Practice implications at the micro, mezzo, and macro levels are discussed. Qualitative and quantitative studies that expand our understanding of women's experience in the military and as veterans are encouraged. PMID- 26833174 TI - Hippocampal dysfunction defines disease onset in Huntington's disease. AB - BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterised by a triad of motor, psychiatric and cognitive deficits with the latter classically attributed to disruption of frontostriatal networks. However, emerging evidence from animal models of HD suggests that some of the early cognitive deficits may have a hippocampal basis. The objective of this study was to link previous rodent findings in this area to clinical practice. METHODS: In this study, 94 participants included patients with early HD, premanifest HD and age-matched controls underwent hippocampal-based cognitive assessments. These included a virtual reality version of the Morris water maze, a task involved participants having to swim through a virtual pool to find a submerged platform using a joystick, and the Cambridge Neuropsychological Test Automated Battery (CANTAB) paired associates learning task, a test also known to rely on hippocampal integrity. RESULTS: Patients with early HD showed impaired performance in both the virtual Morris water maze and the CANTAB paired associates learning. Such deficits were also correlated with estimated years to diagnosis in premanifest participants. CONCLUSIONS: This study highlights the merit of using analogous tests in the laboratory and clinic and demonstrates that hippocampal impairments are an early feature of HD in patients as previously shown in rodent models of the disease. As such, they could be used not only to assist in the diagnosis of disease onset, but may also be useful as an outcome measure in future therapeutic trials. PMID- 26833175 TI - Exploding head syndrome, snapping of the brain or episodic cranial sensory shock? PMID- 26833176 TI - Induced pluripotent stem cells in Parkinson's disease: scientific and clinical challenges. AB - Induced pluripotent stem cells (iPSCs), which greatly circumvent the ethical issue of human embryonic stem cells (ESCs), can be induced to differentiate to dopaminergic (DA) neurons, and hence be used as a human disease model for Parkinson's disease (PD). iPSCs can be also utilised to probe the mechanism, and serve as an 'in vivo' platform for drug screening and for cell-replacement therapies. However, any clinical trial approaches should be extensively supported by validated robust biological evidence (based on previous experience with fetal mesencephalic transplantation), in particular, the production and selection of the 'ideal' neurons (functional units with no oncological risk), together with the careful screening of appropriate candidates (such as genetic carriers), with inbuilt safeguards (safety studies) in the evaluation and monitoring (functional neuroimaging of both DA and non-DA system) of trial subjects. While iPSCs hold great promise for PD, there are still numerous scientific and clinical challenges that need to be surmounted before any clinical application can be safely introduced. PMID- 26833177 TI - What makes home health workers think about leaving their job? The role of physical injury and organizational support. AB - Based on the job demands-resources (JD-R) model, this study explored the role of physical injury and organizational support in predicting home health workers' turnover intention. In a sample of home health workers in Central Texas (n = 150), about 37% reported turnover intention. The logistic regression model showed that turnover intention was 3.23 times more likely among those who had experienced work-related injury. On the other hand, organizational support was found to reduce the likelihood of turnover intention. Findings suggest that injury and organizational support should be prioritized in prevention and intervention efforts to promote home health workers' safety and retention. PMID- 26833178 TI - Effect of Hurricane Sandy on Long Island Emergency Departments Visits. AB - OBJECTIVE: This study aimed to examine the effect of Hurricane Sandy on Long Island mental health emergency department (ED) visits and to determine whether these visits varied according to patient demographics or geographic area and intensity of the impact. METHODS: Individual-level de-identified data were extracted from the Statewide Planning and Research Cooperative System from New York State ED visits from October 1 to December 2012 for residents of Nassau and Suffolk counties in Long Island. The dates of the ED visits were grouped into 4 periods: (1) pre-Sandy, October 1-28; (2) during Sandy, October 29; (3) post Sandy I, October 30 to November 1; and (4) post-Sandy II, November 2-30. RESULTS: A total of 126,337 ED visits were recorded among 23 EDs. A significant drop in volume was observed on October 29; 399 more ED visits for physical health diagnoses were identified in the post-Sandy I period than in the pre-Sandy period. "Diseases of the respiratory system" was the only diagnosis group that showed a positive trend in the post-Sandy I period compared with the pre-Sandy period (increase of 4%). No significant changes in mental health visits were observed after Sandy landfall. CONCLUSIONS: This analysis suggests that the critical temporal window during which ED resources should be increased is in the immediate aftermath of a hurricane. (Disaster Med Public Health Preparedness. 2016;10:344-350). PMID- 26833179 TI - Commentary on the Paper of Walther L. et al.: Phosphatidylethanol is Superior to CDT and GGT as an Alcohol Marker and Is a Reliable Estimate of Alcohol Consumption Level. PMID- 26833180 TI - Relational empathy and holistic care in persons with spinal cord injuries. AB - OBJECTIVE: Describe perceptions of persons with SCI on their receipt of holistic care and relational empathy during health care encounters. DESIGN: Mailed survey. PARTICIPANTS/SETTING: Individuals with SCI who received care from the largest suppliers of SCI care and rehabilitation (Veterans Health Administration and SCI Model Systems). OUTCOME MEASURES: Using a survey and administrative databases, we collected demographic and injury characteristics, health status, health conditions, and the main outcome: Consultation and Relational Empathy (CARE) measure. RESULTS: The sample included 450 individuals with SCI (124 Veterans and 326 civilians). Response rate was 39% (450/1160). Analyses were conducted on patients with complete data (n = 389). Veterans and civilians with SCI differed across many demographic characteristics, age at injury, and etiology, but mean CARE scores were equivalent. Fewer than half of the full SCI cohort had CARE scores above the normative value of 43. Having a recent pressure ulcer showed a trend for lower odds of having a normative or higher CARE score. Odds of having an above-normative CARE score were nearly 2 times greater for individuals with tetraplegia, and odds were higher for those with higher physical and mental health status. CONCLUSIONS: Higher physical and mental health status and tetraplegia were each independently associated with greater perceptions of holistic care and empathy in the therapeutic patient-provider relationship. Limited empathy, communication, and holistic care may arise when providers focus on disease/disease management, rather than on patients as individuals. Frequent health care use and secondary conditions may affect empathy and holistic care in encounters, making it essential to understand and employ efforts to improve the therapeutic relationship between patients with SCI and their providers. PMID- 26833181 TI - Whole genome sequencing revealed host adaptation-focused genomic plasticity of pathogenic Leptospira. AB - Leptospirosis, caused by pathogenic Leptospira spp., has recently been recognized as an emerging infectious disease worldwide. Despite its severity and global importance, knowledge about the molecular pathogenesis and virulence evolution of Leptospira spp. remains limited. Here we sequenced and analyzed 102 isolates representing global sources. A high genomic variability were observed among different Leptospira species, which was attributed to massive gene gain and loss events allowing for adaptation to specific niche conditions and changing host environments. Horizontal gene transfer and gene duplication allowed the stepwise acquisition of virulence factors in pathogenic Leptospira evolved from a recent common ancestor. More importantly, the abundant expansion of specific virulence related protein families, such as metalloproteases-associated paralogs, were exclusively identified in pathogenic species, reflecting the importance of these protein families in the pathogenesis of leptospirosis. Our observations also indicated that positive selection played a crucial role on this bacteria adaptation to hosts. These novel findings may lead to greater understanding of the global diversity and virulence evolution of Leptospira spp. PMID- 26833183 TI - miR-34a inhibits the apoptosis of MDSCs by suppressing the expression of N-myc. AB - Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of early myeloid progenitors, which possess strong immunosuppressive functions. MDSCs are found in increased numbers in infectious and inflammatory pathological conditions. However, whether microRNAs have a role in the expansion remains unclear. Here in our study, we found that overexpression of miR-34a could induce the expansion of MDSCs in the bone marrow and spleen both in chimera and transgenic mice. And further experiments demonstrated that miR-34a inhibited the apoptosis through reduced translation of N-myc without affecting the proliferation. Luciferase assay and western blotting experiments implied that N myc is the direct target of miR-34a in MDSCs. Overexpressed mir-34a changes the cytokine expression profile in MDSCs and skewed the MDSCs to M1 phenotype. And miR-34a-overexpressed MDSCs significantly slowed down the tumor growth. Taken together, miR-34a contributes to the expansion of MDSCs by inhibiting the apoptosis via suppressing the expression of N-myc. PMID- 26833182 TI - Genome-Wide Meta-Analysis of Cotinine Levels in Cigarette Smokers Identifies Locus at 4q13.2. AB - Genome-wide association studies (GWAS) of complex behavioural phenotypes such as cigarette smoking typically employ self-report phenotypes. However, precise biomarker phenotypes may afford greater statistical power and identify novel variants. Here we report the results of a GWAS meta-analysis of levels of cotinine, the primary metabolite of nicotine, in 4,548 daily smokers of European ancestry. We identified a locus close to UGT2B10 at 4q13.2 (minimum p = 5.89 * 10(-10) for rs114612145), which was consequently replicated. This variant is in high linkage disequilibrium with a known functional variant in the UGT2B10 gene which is associated with reduced nicotine and cotinine glucuronidation activity, but intriguingly is not associated with nicotine intake. Additionally, we observed association between multiple variants within the 15q25.1 region and cotinine levels, all located within the CHRNA5-A3-B4 gene cluster or adjacent genes, consistent with previous much larger GWAS using self-report measures of smoking quantity. These results clearly illustrate the increase in power afforded by using precise biomarker measures in GWAS. Perhaps more importantly however, they also highlight that biomarkers do not always mark the phenotype of interest. The use of metabolite data as a proxy for environmental exposures should be carefully considered in the context of individual differences in metabolic pathways. PMID- 26833184 TI - Rhabdomyolysis after bariatric surgery: a multicenter, prospective study on incidence, risk factors, and therapeutic strategy in a cohort from South Italy. AB - BACKGROUND: At present, prospectively collected data on rhabdomyolysis (RML) after bariatric surgery are limited. OBJECTIVES: To evaluate the incidence, risk factors, and therapeutic strategy of RML in different bariatric procedures. SETTING: University hospitals, Italy. METHODS: Obese patients were prospectively enrolled. Preoperative demographic characteristics and clinical data, as well as type of anesthesia and type and total duration of surgery, were recorded as potential risk factors for RML. RML was defined as postoperative creatine kinase (CK)>1000 U/L. Incidence, possible risk factors, and therapeutic outcome of RML were assessed and compared with comparative groups. RESULTS: Four hundred eighty obese patients were included in the study. After surgery, RML was diagnosed in 62 (12.9%) patients. Muscular pain was present in 12 patients (19.3%). In RML patients, mean CK value was 1346+/-2132.5 U/L (range 1191-37,400). Only duration of surgery was identified as an independent risk factor for RML (P<.001). The best cutoff value of time as a predictor was 230 minutes. Aggressive therapy with fluids and diuretics started within 24 hours after surgery was more effective in relieving RML and muscle pain than a comparative retrospective group with a delayed diagnosis and therapy. CONCLUSION: After bariatric surgery, the risk of RML increases, especially when the duration of surgery is>230 minutes. CK testing should be performed in all patients after bariatric surgery to make an early diagnosis and properly start fluids and diuretics. PMID- 26833185 TI - Predictors of long-term success after laparoscopic Roux-en-Y gastric bypass in African-American women. AB - BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) provides sustained weight loss. However, short-term studies have suggested that African Americans (AAs) are not as successful as Caucasians (CAs) after LRYGB. OBJECTIVE: The present study was designed to test the hypothesis that at longer term follow-up AAs are just as successful as CAs after LRYGB. SETTING: University hospital, United States. METHODS: A nested case-control study designed to examine the effect of race as covariate in the long-term success of women undergoing LRYGB. The study matched 3 controls per case subject, and the final numbers for analyses were 78 case patients (AA) and 204 control patients (CA). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression analysis. RESULTS: The 2 cohorts (N = 282) were well matched for age (AA 40.3+/-9.1 years versus CA 41.1+/-8.9 years), preoperative body mass index (AA 50.6+/-7.5 kg/m(2) versus CA 50.2+/-7.1 kg/m(2)), prevalence of type 2 diabetes (T2D) (AA 20.5% versus CA 21.1%), hypertension (AA 69.1% versus CA 52%), and sleep apnea (AA 35.9% versus CA 34.8%). In the AA group, the long-term curve for percentage of excess weight loss (EWL) was significantly (P<.001) lower than the CA group at any time-point. In the present model, diagnosis of T2D in the AA group (OR = 6.1 E8) significantly (P = .002) predicted adequate EWL at 3 years, after controlling for relevant confounders. CONCLUSION: Race significantly affected the long-term EWL at 3 years for patients undergoing LRYGB at the authors' institution. Future research should be directed at determining potential genetic reasons for these differences, including genes associated with T2D. PMID- 26833188 TI - Printed microelectrodes for scalable, high-areal-capacity lithium-sulfur batteries. AB - Printed microelectrodes for lithium-sulfur cathodes are produced with aqueous inks and a one-step printing process. The cathodes exhibit high areal capacities of >=5 mA h cm(-2) for 50 cycles and withstand >=500 cycles. This performance meets energy-storage benchmarks for powering microdevices, and presents a strategic option for future microbatteries. PMID- 26833186 TI - Anastomotic techniques in open Roux-en-Y gastric bypass: primary open surgery and converted procedures. AB - BACKGROUND: Open Roux-en-Y gastric bypass (RYGB) may be chosen because of known widespread adhesions or as a result of conversion during laparoscopic surgery. Although conversions are rare, they occur even in experienced hands. The gastrojejunostomy may be performed with a circular stapler (CS) or a linear stapler (LS) or may be entirely hand sewn (HS). Our aim was to study differences in outcomes regarding the anastomotic techniques utilized in open surgery. SETTING: Nationwide cohort. METHODS: Data on open surgery, both primary open and converted procedures from Scandinavian Obesity Surgery Registry were analyzed for the years 2007-2013. Outcomes were assessed through multivariate analysis, adjusting for gender, age, preoperative body mass index, diabetes, conversion, and technique used for the gastrojejunostomy. RESULTS: CS was the most common method used for primary open RYGB (58%), whereas LS was the most common for converted RYGB (63%). HS was uncommon in both groups. Operative time was shorter for LS than for CS in the primary open RYGB (110+/-40 min versus 132+/-46 min; P<.001). Anastomotic leakage rates were similar in primary open RYGB (1.0%-2.4%), but leakage rates for LS in converted procedures was 10.1%, thus higher compared with 2.1% in converted CS patients (P = .02). Odds ratio for leakage was 2.87 (95% confidence interval 1.18-6.97) for LS using CS as a reference when adjusting for variables above. CONCLUSION: LS was associated to increased risk of leakage in patients with conversion from laparoscopic RYGB to open RYGB. Conversion to open surgery was associated to increased risk of leakage. Technique used for the gastrojejunostomy did not affect weight loss. PMID- 26833189 TI - The treatment of complex proximal humeral fractures: analysis of the results of 55 cases treated with PHILOS plate. AB - Complex proximal humerus fractures are often difficult to treat. Their frequency is high, especially in the elderly, and their treatment is still controversial. The aim of this study was to analyze the clinical and radiological results achieved by patients with complex proximal humerus fractures, treated with PHILOS plate only. A cohort of 55 patients was selected. The mean age was 63.4 (range 33 89), while the mean follow-up time was 21.5 months (range 6-75). Clinical outcome was evaluated with the "Constant-Murley shoulder score." All the informations about the presence of complications were gathered, and radiological images were used to calculate the head-shaft angle. The overall mean Constant score was 61.93 +/- 18.59, the Individual CS was 70 +/- 20 % and the Relative CS was 83 +/- 23 %. No significant differences were found between fractures Neer 3 and Neer 4 and between the surgical approaches (delta-split vs. delto-pectoral). Six patients had a fracture with dislocation, seven patients (12.7 %) had complications while in four patients a head-shaft angle beyond the normal range was found. Osteosynthesis with PHILOS plate is stable in the greater part of the cases, and it allows an earlier rehabilitation and so a good functional result, which could be compromised by a prolonged immobilization. Therefore, PHILOS plate is a good option for the treatment of complex proximal humerus fractures. PMID- 26833190 TI - Pontibacter locisalis Sy30T sp. nov. isolated from soil collected from an abandoned saltern. AB - A novel Gram-stain negative, red, rod-shaped, non-motile and aerobic bacterial strain, designated Sy30(T), was isolated from dry soils of an abandoned marine saltern at Weihai, China. 16S rRNA sequence analysis indicated that strain Sy30(T) belongs to the genus Pontibacter in the family Cytophagaceae, with sequence similarities ranging from 93.3 to 96.4 % with other type species of the genus Pontibacter. The predominant cellular fatty acids were iso-C15:0 and summed feature 4 (iso-C17:1 I and/or anteiso-C17:1 B). The major menaquinone was MK-7. The major polyamine was sym-homospermidine. The DNA G+C content was 47.7 mol%. The major polar lipids consisted of phosphatidylethanolamine, phosphoaminolipid and two unidentified polar lipid. Based on phenotypic, chemotaxonomic and phylogenetic analysis, strain Sy30(T) represents a novel species of the genus Pontibacter in the family Cytophagaceae, phylum Bacteroidetes, for which the name Pontibacter locisalis sp. nov. is proposed. The type strain is Sy30(T) (=KCTC 42498(T) = CICC AB 2015060(T)). PMID- 26833191 TI - Chemical constituents with anti-allergic activity from the root of Edulis Superba, a horticultural cultivar of Paeonia lactiflora. AB - The methanolic extract and its subfractions from the dried root of Edulis Superba, a horticultural cultivar of Paeonia lactiflora Pallas, showed potent anti-allergic effect as inhibition of immunoglobulin E (IgE)-mediated degranulation in rat basophil leukemia (RBL)-2H3 cells. Bioassay-guided fractionation led to the isolation of 26 compounds, including a new norneolignan glycoside, paeonibenzofuran (1), together with 25 known ones (2-26). The chemical structure of the new compound was elucidated on the basis of spectroscopic and chemical evidences. Among the isolated compounds, mudanpioside E (5) with paeoniflorin-type skeleton and quercetin (16) showed potent inhibitory activity against a degranulation marker, beta-hexosaminidase release with IC50 values of 40.34 and 25.05 MUM, respectively. A primary structure-activity relationship of these components was discussed. PMID- 26833192 TI - Comparative analysis of the constituents in Saposhnikoviae Radix and Glehniae Radix cum Rhizoma by monitoring inhibitory activity of nitric oxide production. AB - During the development of natural herbal medicines in Japan, Glehniae Radix cum Rhizoma (Hamabofu in Japanese) has been used as a substitute for Saposhnikoviae Radix (Bofu). Bofu and Hamabofu are blended differently in several Kampo formulae. For example, Bofu is included in Jumihaidokuto by a manufacturer, whereas Hamabofu is included instead of Bofu in the same formula by other manufacturers. Although both Bofu and Hamabofu are used for their expected anti inflammatory effects, differences in their medicinal properties are not well characterized. In addition, there have been very few reports comparing the pharmacological activities of the constituents in Bofu and Hamabofu. In the present study, we investigated the anti-inflammatory effects of the extracts of Bofu and Hamabofu by monitoring levels of the inflammatory mediator nitric oxide (NO) produced in rat hepatocytes. Moreover, the chemical constituents responsible for the activity were investigated. Our results showed that ethyl acetate fractions of Bofu and Hamabofu extracts contain different compounds, although both fractions suppressed NO production in rat hepatocytes. The linear dihydropyranochromones from the Bofu extract (i.e., 3'-O-angeloylhamaudol, ledebouriellol and hamaudol) suppressed NO production, whereas the coumarins from the Hamabofu extract (i.e., umbelliferone and scopoletin) also suppressed NO production. These results suggest that linear dihydropyranochromones and coumarins are responsible for the anti-inflammatory effects of Bofu and Hamabofu. It is plausible that Bofu and Hamabofu are blended differently in several Kampo formulae due to many constituents with as yet unidentified pharmacological activity. PMID- 26833193 TI - Oxidative stress does not play a primary role in the toxicity induced with clinical doses of doxorubicin in myocardial H9c2 cells. AB - The implication of oxidative stress as primary mechanism inducing doxorubicin (DOX) cardiotoxicity is still questionable as many in vitro studies implied supra clinical drug doses or unreliable methodologies for reactive oxygen species (ROS) detection. The aim of this study was to clarify whether oxidative stress is involved in compliance with the conditions of clinical use of DOX, and using reliable tools for ROS detection. We examined the cytotoxic mechanisms of 2 MUM DOX 1 day after the beginning of the treatment in differentiated H9c2 rat embryonic cardiac cells. Cells were exposed for 2 or 24 h with DOX to mimic a single chronic dosage or to favor accumulation, respectively. We found that apoptosis was prevalent in cells exposed for a short period with DOX: cells showed typical hallmarks as loss of anchorage ability, mitochondrial hyperpolarization followed by the collapse of mitochondrial activity, and nuclear condensation. Increasing the exposure period favored a shift to necrosis as the cells preferentially exhibited early DNA impairment and nuclear swelling. In either case, measuring the fluorescence lifetime of 1-pyrenebutyric acid or the intensities of dihydroethidium or amplex red showed a consistent pattern in ROS production which was a slight increased level far from representative of an oxidative stress. Moreover, pre-treatment with dexrazoxane provided a cytoprotective effect although it failed to detoxify ROS. Our data support that oxidative stress is unlikely to be the primary mechanism of DOX cardiac toxicity in vitro. PMID- 26833194 TI - GADD45alpha modulates curcumin sensitivity through c-Abl- and JNK-dependent signaling pathways in a mismatch repair-dependent manner. AB - Colorectal cancer is a critical health concern because of its incidence as the third most prevalent cancer in the world. Currently, 5-fluorouracil (5-FU), 6 thioguanine, and certain other genotoxic agents are mainstays of treatment; however, patients often die due to emergence of resistant population. Curcumin, a bioactive compound derived from the dietary turmeric (Curcuma longa) is an effective anticancer, anti-inflammatory, and antioxidant agent. Previously, we reported that human colorectal cancer cell lines compromised for mismatch repair (MMR) function exhibit heightened sensitivity to curcumin due to sustained curcumin-induced unrepaired DNA damage compared to proficient population counterparts. In this report, we show that the protein levels of gadd45alpha, whose transcript levels are increased during DNA damage and stress signals, are upregulated following curcumin treatment in a dose- and time-dependent manner. We further observed that cells compromised for Mlh1 function (HCT116 + Ch2) displayed ~twofold increased GADD45alpha upregulation compared to similarly treated proficient counterparts (HCT116 + Ch3). Similarly, suppression of Mlh1 using ShRNA increased GADD45alpha upregulation upon curcumin treatment. On the other hand, suppression of GADD45alpha using SiRNA-blocked curcumin-induced cell death induction in Mlh1-deficient cells. Moreover, inhibition of Abl through ST571 treatment and its downstream effector JNK through SP600125 treatment blocked GADD45alpha upregulation and cell death triggered by curcumin. Collective results lead us to conclude that GADD45alpha modulates curcumin sensitivity through activation of c-Abl > JNK signaling in a mismatch repair-dependent manner. PMID- 26833197 TI - The Editor welcomes the newly appointed members of the Advisory Board. PMID- 26833196 TI - Anti-leukemic, anti-lung, and anti-breast cancer potential of the microbial polyketide 2, 4-diacetylphloroglucinol (DAPG) and its interaction with the metastatic proteins than the antiapoptotic Bcl-2 proteins. AB - The microbial polyketide, 2, 4-diacetylphloroglucinol (DAPG), exhibited a broad spectrum of anti-leukemic, anti-lung, and anti-breast cancer properties. The aim of the present investigation was to study the interactive potentials of DAPG with the metastatic proteins such as MMP-2, MMP-9, and NF-kappaB and antiapoptotic Bcl 2 family proteins such as Bcl-2, Bcl-w, and Bcl-xL through in silico interaction and in vitro studies. The in silico modeling predicted high interactions of DAPG with the metastatic proteins, especially MMP-2, MMP-9, and NF-kappaB with the glide score of -7.028, -6.304, and -5.231, respectively. Similarly, the DAPG had weak interactions with the antiapoptotic Bcl-2, Bcl-w, and Bcl-xL with the glide score of -4.505, -3.839, and -4.003, respectively. The interaction studies further revealed the inhibition of MMP-2, MMP-9, and NF-kappaB activities with the low IC50 concentration of 5.82 +/- 1.6, 6.74 +/- 1.2, and 10.7 +/- 1.5 MUM respectively, in the presence of DAPG. Similarly, DAPG inhibited the Bcl-2, Bcl xL and Bcl-w activities with the high IC50 concentration of 29.8 +/- 1.9, 85.9 +/ 2.7, and 97.4 +/- 1.5 MUM, respectively. These results correlate with the relatively high IC50 concentration of 16.3 +/- 1.76, 7.67 +/- 0.78, and 10.7 +/- 0.96 MUM in the Bcl-2-overexpressing HL-60, K562 and Raji leukemic cells than the metastatic A549 and MDA MB-231 cancer cells with the low IC50 concentration of 0.06 +/- 0.02 and 0.08 +/- 0.01 MUM, respectively, compared to the healthy, human embryonic kidney (HEK-293) cells with the high IC50 concentration of 54.7 +/- 1.43 MUM. In summary, the affinity of DAPG with proteins are in the order of MMP 2 > MMP-9 > NF-kappaB > Bcl-2 > Bcl-xL > Bcl-w. Results presented in this study confirmed the high interaction of DAPG with the metastatic proteins than the antiapoptotic Bcl-2 family proteins. PMID- 26833195 TI - MicroRNA-128 regulates the proliferation and differentiation of bovine skeletal muscle satellite cells by repressing Sp1. AB - MicroRNAs (miRNAs) play essential roles in muscle cell proliferation and differentiation. The muscle-specific miRNAs miR-1 and miR-206 have been shown to regulate muscle development and promote myogenic differentiation; however, it is likely that a number of other miRNAs play important roles in regulating myogenesis as well. microRNA-128 (miR-128) has been reported to be highly expressed in brain and skeletal muscle, and we found that miR-128 is also up regulated during bovine skeletal muscle satellite cell differentiation using microarray analysis and qRT-PCR. However, little is known about the functions of miR-128 in bovine skeletal muscle satellite cell development. In this study, we investigated the biological functions of miR-128 in bovine skeletal muscle cell development. Using a dual-luciferase reporter assay, we confirmed that miR-128 regulates the Sp1 gene. Over-expression of miR-128 reduced Sp1 protein levels and inhibited muscle satellite cell proliferation and differentiation. Inhibition of miR-128 increased Sp1 protein levels and promoted muscle satellite cell differentiation but also suppressed proliferation. Changes in miR-128 and Sp1 expression levels also affected the protein levels of MyoD and CDKN1A. Sp1, an activator of MyoD and a suppressor of CDKN1A, plays an important role in bovine muscle cell proliferation and differentiation. The results of our study reveal a mechanism by which miR-128 regulates bovine skeletal muscle satellite cell proliferation and myogenic differentiation via Sp1. PMID- 26833200 TI - Investigating a method for reducing residual switch costs in cued task switching. AB - Residual switch costs in cued task switching are performance decrements that occur despite a long cue-target interval (CTI) to prepare for a task switch. Verbruggen, Liefooghe, Vandierendonck, and Demanet (Journal of Experimental Psychology: Learning, Memory, and Cognition, 33; 342-356, 2007) showed that briefly presenting the cue during the CTI and leaving it absent after target onset yielded smaller residual switch costs than those obtained when the cue was available for the full CTI and remained present after target onset. The potential effects of cue availability during the CTI (full or partial) and cue status after target onset (present or absent) on residual switch costs were investigated in the present study. In Experiments 1 and 2, cue status was manipulated while holding cue availability constant. In Experiments 3 and 4, cue status and cue availability were manipulated factorially. Residual switch costs were obtained, but they were not modulated consistently by cue status or cue availability across experiments. In Experiment 5, a direct replication of one of Verbruggen and colleagues' experiments yielded divergent results. Implications for understanding task switching are discussed. PMID- 26833201 TI - Pollutant Concentrations and Toxic Effects on the Red Alga Ceramium tenuicorne of Sediments from Natural Harbors and Small Boat Harbors on the West Coast of Sweden. AB - This investigation set out to analyze the toxicity of surface sediments in a number of natural harbors and small boat harbors on the west coast of Sweden. This was done with the growth inhibition method with Ceramium tenuicorne. Also, concentrations of copper (Cu), lead (Pb), zinc (Zn), irgarol, organotin compounds, and polycyclic aromatic hydrocarbons (PAHs) in the sediments were analyzed. The small boat harbors were heavily polluted by Cu, Zn, butyltins, and PAHs, and to a lesser extent by Pb. The Cu, Pb, Zn, and butyltins probably originated from their past and/or present use in antifouling paints, whereas the PAHs probably had multiple sources, including boat motor exhausts. The measured toxicity of the sediment was generally related to their Cu, Zn, and butyltin content, although other toxic substances than those analyzed here probably contributed to the toxicity in some of the harbors. The natural harbor sediments contained less pollutants and were less toxic than the small boat harbor sediments. Nevertheless, our data indicate that the boating pressure today may be high enough to produce toxic effects even in natural harbors in pristine areas. The strongest relationship between toxicity and the major pollutants was obtained when the sediment toxicity was expressed as gram wet weight per liter compared with gram dry weight per liter and gram total organic carbon per liter. Hence, for pollutants that can be elutriated with natural sea water, sediment toxicity expressed as gram wet weight per liter appears preferable. PMID- 26833199 TI - Alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV. AB - The incidence of hepatocellular carcinoma (HCC) is closely correlated with hepatitis B virus (HBV)-induced liver cirrhosis. Structural changes in the glycans of serum and tissue proteins are reliable indicators of liver damage. However, little is known about the alteration of liver glycopatterns during cirrhosis and tumor progression induced by HBV infection. This study compared the differential expression of liver glycopatterns in 7 sets of normal pericarcinomatous tissues (PCTs), cirrhotic, and tumor tissues from patients with liver cirrhosis and HCC induced by HBV using lectin microarrays. Fluorescence based lectin histochemistry and lectin blotting were further utilized to validate and assess the expression and distribution of certain glycans in 9 sets of corresponding liver tissue sections. Eight lectins (e.g., Jacalin and AAL) revealed significant difference in cirrhotic tissues versus PCTs. Eleven lectins (e.g., EEL and SJA) showed significant alteration during cirrhotic and tumor progression. The expression of Galalpha1-3(Fucalpha1-2)Gal (EEL) and fucosyltransferase 1 was mainly increasing in the cytoplasm of hepatocytes during PCTs-cirrhotic-tumor tissues progression, while the expression of T antigen (ACA and PNA) was decreased sharply in cytoplasm of tumor hepatocytes. Understanding the precision alteration of liver glycopatterns related to the development of hepatitis, cirrhosis, and tumor induced by HBV infection may help elucidate the molecular mechanisms underlying the progression of chronic liver diseases and develop new antineoplastic therapeutic strategies. PMID- 26833202 TI - Bioaccumulation of Legacy and Emerging Organochlorine Contaminants in Lumbriculus variegatus. AB - Freshwater sediment-dwelling Lumbriculus variegatus is known to serve as a vector for the transfer of contaminants from sediments to higher trophic level organisms, but limited data exist on the bioaccumulation of chemicals associated with sediments containing high total organic carbon (TOC). In the current study, sediments from the north shore area of Lake Apopka (Florida, USA), containing very high TOC [39 % (w/w)], were spiked with four chemicals-p,p' dichlorordiphenyldichloroethylene (p,p'-DDE), dieldrin, fipronil, and triclosan individually or in a mixture of the four and then used for bioaccumulation studies. Tissue concentrations of chemicals in L. variegatus were measured at 2, 7, 14, 21, and 28 days of exposure, and the bioaccumulation potential was evaluated using biosediment accumulation factors [BSAF (goc/glipid)]. Increase in total body burdens of all four chemicals in L. variegatus was rapid at day 2 and reached a steady-state level after 7 days in both single and mixture experiments. Tissue concentrations of fipronil peaked after 2 days and then decreased by 70 % in sediment experiments suggesting that in addition to the degradation of fipronil that occurred in the sediment, L. variegatus may also be able to metabolize fipronil. The calculated 28-day BSAF values varied among the chemicals and increased in the order fipronil (1.1) < triclosan (1.4) < dieldrin (21.8) < p,p'-DDE (49.8) in correspondence with the increasing degree of their hydrophobicity. The relatively high BSAF values for p,p'-DDE and dieldrin probably resulted from lower-than-expected sorption of chemicals to sediment organic matter either due to the nature of the plant-derived organic matter, as a result of the relatively short equilibration time among the various compartments, or due to ingestion of sediment particles by the worms. PMID- 26833203 TI - Communication and integration: a qualitative analysis of perspectives among Middle Eastern oncology healthcare professionals on the integration of complementary medicine in supportive cancer care. AB - CONTEXT AND OBJECTIVES: The use of complementary and traditional medicine (CTM ) in Middle Eastern countries is widespread, including among patients with cancer. Perspectives of oncology healthcare professionals (HCPs) in this region regarding the integration of CTM within conventional supportive cancer care were explored. METHODS: An 11-item questionnaire with an open-ended question asking respondents to comment about the integration of CTM within supportive cancer care was sent to Middle Eastern oncology HCPs, using snowball sampling methodology. The narratives provided were examined using thematic analysis. RESULTS: A total of 339 oncology HCPs completed and returned the study tool (80.3 % response rate ), of which 178 from 15 Middle Eastern countries responded to the open-ended question. The majority of respondents are in favor of the integration of CTM within supportive cancer care, though ideas on how this should be implemented varied. Thematic analysis identified multifactorial barriers to integration, which focused on HCPs' perspectives (e.g., a lack of knowledge and training; a skeptical approach to CTM), attitudes of patients and caregivers (e.g., unrealistic expectations regarding the outcomes of CTM treatments) and HCP-patient communication. In order to overcome these barriers, respondents suggested education and training programs for oncology HCPs which would focus on improving patients' quality-of-life related outcomes. CONCLUSIONS: Middle Eastern oncology HCPs support the integration of CTM within supportive cancer care, while recognizing the need for education and training in this field. A better understanding of CTM would provide the knowledge and skills which would promote a non-judgmental, evidence-based approach, fostering better communication with patients. PMID- 26833204 TI - Hybridized Phosphate with Ultrathin Nanoslices and Single Crystal Microplatelets for High Performance Supercapacitors. AB - A novel hybridized phosphate is developed through a mild hydrothermal method to construct high performance asymmetric supercapacitor. Single layered (Ni,Co)3(PO4)2.8H2O nanoslices (~1 nm) and single crystal (NH4)(Ni,Co)PO4.0.67H2O microplatelets are obtained through a template sacrificial method and dissolution recrystallization approach respectively in one step. This unique hybridized structure delivers a maximum specific capacitance of 1128 F g(-1) at current density of 0.5 A g(-1). The asymmetric supercapacitor (ASC) based on the hybrid exhibits a high energy density of 35.3 Wh kg(-1) at low power density, and still holds 30.9 Wh kg(-1) at 4400 W kg(-1). Significantly, the ASC manifests very high cycling stability with 95.6% capacitance retention after 5000 cycles. Such excellent electrochemical performance could be attributed to the synergistic effect of the surface redox reaction from the ultrathin nanoslices and ion intercalation from the single crystal bulk structure. This material represents a novel kind of electrode material for the potential application in supercapacitors. PMID- 26833205 TI - Adult childhood cancer survivors' narratives of managing their health: the unexpected and the unresolved. AB - PURPOSE: Currently, 80 % of children diagnosed with cancer will be cured. However, many of these survivors go on to develop long-term health problems or late effects related to their previous cancer and therapy and require varying degrees of lifelong follow-up care. The purpose of this study was to identify the different ways that adult survivors of childhood cancer manage their medical and psychological challenges. METHODS: Data from in-depth interviews with 30 adult survivors of a childhood cancer (9 to 38 years after diagnosis, currently 22 to 43 years of age, 60 % women) were analyzed using qualitative, thematic narrative analysis methods. RESULTS: The survivors had not expected the medical, psychological, and social challenges that arose over time and that often remained unresolved. Five narrative themes revealed distinct ways that survivors managed their health challenges: (1) trying to forget cancer, (2) trusting the system to manage my follow-up care, (3) being proactive about my health, (4) stumbling from one problem to the next, and (5) struggling to find my way. CONCLUSIONS: Variation exists in the ways in which childhood cancer survivors frame their health, their perceived significance of health challenges, strategies used to manage health, interactions with healthcare professionals and the health system, and parental involvement. IMPLICATIONS FOR CANCER SURVIVORS: This research provides novel insights that can be used to inform the development of patient centered health services that promote the assessment and tailoring of care to the diverse ways survivors enact their agency, as well as their psychoeducational coping styles, therapeutic relationship needs, and information needs. PMID- 26833206 TI - Promoting community readiness for physical activity among older adults in Germany -protocol of the ready to change intervention trial. AB - BACKGROUND: Healthy ageing is an important concern for many societies facing the challenge of an ageing population. Physical activity (PA) is a major contributor to healthy ageing; however insufficient PA levels are prevalent in old age in Germany. Community capacity building and community involvement are often recommended as key strategies to improve equitable access to prevention and health promotion. However, evidence for the effectiveness of these strategies is scarce. This study aims to assess the community readiness for PA promotion in local environments and to analyse the utility of strategies to increase community readiness for reaching vulnerable groups. METHODS/DESIGN: We designed a mixed method intervention trial comprising three study modules. The first module includes an assessment of community readiness for PA interventions in older adults. The assessment is carried out in a sample of 24 municipalities in the Northwest of Germany using structured key informant interviews. In the second module, eight municipalities with the low community readiness are selected from the sample and randomly assigned to one of two study groups: active enhancement of community readiness (intervention) versus no enhancement (control). After enhancing community readiness in the active enhancement group, older adults in both study groups will be recruited for participation in a PA intervention. Participation rates are compared between the study groups to evaluate the effects of the intervention. In addition, a cost-effectiveness analysis is carried out calculating recruitment costs per person reached in the two study groups. In the third module, qualitative interviews are conducted with participants and non participants of the PA intervention exploring reasons for participation or non participation. DISCUSSION: This study offers the potential to contribute to the evidence base of reaching vulnerable older adults for PA interventions and provide ideas on how to reduce participation barriers. Its findings will inform governmental authorities, professionals, academics, and NGOs with an estimate of resources necessary to achieve equitable access to physical activity programs for vulnerable older adults. TRIAL REGISTRATION: German Clinical Trials Register DRKS00009564 (Date of registration 03-11-2015). PMID- 26833207 TI - Treatment of Massive or Submassive Acute Pulmonary Embolism With Catheter Directed Thrombolysis. AB - The presentation of acute pulmonary thromboembolism (PE) can be highly variable resulting in diagnostic challenges and management difficulties. Current guidelines suggest that therapy must be adjusted based on the severity of PE presentation. Systemic thrombolysis is the standard therapy for acute massive PE; however, systemic thrombolysis carries an estimated 20% risk of major hemorrhage, including a 3% to 5% risk of hemorrhagic stroke. There are data supporting the use of catheter-directed therapy (CDT) in massive and submassive PE, but past studies have limited its use to patients in whom systemic thrombolysis has either failed or was contraindicated. There is a paucity of data comparing the efficacy of CDT compared to systemic thrombolysis in different risk groups. This review will summarize the available data on the techniques and indications and outcomes of CDT for acute PE. PMID- 26833208 TI - Tricuspid Regurgitation and Mortality in Patients With Transvenous Permanent Pacemaker Leads. AB - Estimates of the prevalence and importance of significant tricuspid regurgitation (STR) related to implantable device leads are based mainly on case reports, small observational studies, or mixed samples that include defibrillators. We sought to assess whether patients with permanent pacemaker (PPM) leads have an increased risk of STR and to determine mortality associated with PPM-related TR in a large longitudinal single-center cohort. We examined the prevalence of STR (defined as moderate-severe or >=3+) among all echocardiograms performed from 2005 to 2011 excluding those with defibrillators. We then examined mortality risk according to the prevalence of PPM and STR after adjusting for cardiac co-morbidities, left ventricular systolic/diastolic function, and pulmonary artery hypertension. We screened 93,592 echocardiograms (1,245 with PPM) in 58,556 individual patients (634 with PPM). The prevalence of STR was higher in patients after PPM placement (mean age 79 +/- 3 years; 54% men) compared with those without a PPM (adjusted odds ratio 2.32; 95% confidence interval [CI] 1.54 to 3.49; p <0.0001). Among patients with a PPM lead, the presence of STR was associated with increased mortality (adjusted hazard ratio 1.40; 95% CI 1.04 to 2.11, p = 0.027, vs no STR). Compared with having neither a PPM lead nor STR, adjusted hazard ratios for death were 2.13 (95% CI 1.93 to 2.34) for STR but no PPM, 1.04 (0.89 to 1.22) for PPM without STR, and 1.55 (1.13 to 2.14) for PPM with STR. In conclusion, in a sample comprising >58,000 individual patients, PPM leads are associated with higher risk of STR after adjustment for left ventricular systolic/diastolic function and pulmonary artery hypertension; similarly to STR from other cardiac pathologies, PPM-related STR is associated with increased mortality. PMID- 26833209 TI - Medical Assistant-Based Care Management for High-Risk Patients in Small Primary Care Practices: A Cluster Randomized Clinical Trial. AB - BACKGROUND: Patients with multiple chronic conditions are at high risk for potentially avoidable hospitalizations, which may be reduced by care coordination and self-management support. Medical assistants are an increasingly available resource for patient care in primary care practices. OBJECTIVE: To determine whether protocol-based care management delivered by medical assistants improves care in patients at high risk for future hospitalization in primary care. DESIGN: Two-year cluster randomized clinical trial. (Current Controlled Trials: ISRCTN56104508). SETTING: 115 primary care practices in Germany. PATIENTS: 2076 patients with type 2 diabetes, chronic obstructive pulmonary disease, or chronic heart failure and a likelihood of hospitalization in the upper quartile of the population, as predicted by an analysis of insurance data. INTERVENTION: Protocol based care management, including structured assessment, action planning, and monitoring delivered by medical assistants, compared with usual care. MEASUREMENTS: All-cause hospitalizations at 12 months (primary outcome) and quality-of-life scores (12-Item Short Form Health Survey [SF-12] and EuroQol instrument [EQ-5D]). RESULTS: Included patients had an average of 4 co-occurring chronic conditions. All-cause hospitalizations did not differ between groups at 12 months (risk ratio [RR], 1.01 [95% CI, 0.87 to 1.18]) and 24 months (RR, 0.98 [CI, 0.85 to 1.12]). Quality of life (differences, 1.16 [CI, 0.24 to 2.08] on SF 12 physical component and 1.68 [CI, 0.60 to 2.77] on SF-12 mental component) and general health (difference on EQ-5D, 0.03 [CI, 0.00 to 0.05]) improved significantly at 24 months. Intervention costs totaled $10 per patient per month. LIMITATION: Small number of primary care practices and low intensity of intervention. CONCLUSION: This low-intensity intervention did not reduce all cause hospitalizations but showed positive effects on quality of life at reasonable costs in high-risk multimorbid patients. PRIMARY FUNDING SOURCE: AOK Baden-Wurttemberg and AOK Bundesverband. PMID- 26833210 TI - Evaluation of pleiotropic effects among common genetic loci identified for cardio metabolic traits in a Korean population. AB - BACKGROUND: The genetic contribution to complex diseases or traits, including cardio-metabolic traits, has been elucidated recently by large-scale genome-wide association studies. These genome-wide association studies have indicated that most pleiotropic loci contain genes associated with lipids. Clinically, lipid related abnormalities are strongly associated with other diseases such as type 2 diabetes, coronary artery disease and hypertension. The aim of this study was to evaluate the shared genetic background of lipids and other cardio-metabolic traits. METHODS: We conducted meta-analyses of the association between 157 published lipid-associated loci and 10 cardio-metabolic traits in 14,028 Korean individuals genotyped using the Exome chip (Illumina HumanExome BeadChip). We also examined whether the pleiotropic effects of such loci constituted independent (i.e., biological) pleiotropy or mediated pleiotropy in these metabolic pathways. RESULTS: Eighteen lipid-associated loci were significantly associated with one of six cardio-metabolic traits after correction for multiple testing (P < 3.70 * 10(-4)). Region 12q24.12 had pleiotropic effects on fasting plasma glucose, blood pressure and obesity-related traits (body mass index and waist-hip ratio) independent of its effects on the lipid profile. Lipid risk scores, calculated according to whether or not subjects carried the risk allele for lipid traits, were significantly associated with fasting plasma glucose, blood pressure and obesity-related traits. CONCLUSIONS: The 12q24.12 region showed ethnic-specific genetic pleiotropy among cardio-metabolic traits in this study. Our findings may help to account for molecular mechanisms based on shared genetic background underlying not only dyslipidemia, but also cardiovascular disease and type 2 diabetes. PMID- 26833211 TI - Feeding Style and a Child's Body Mass Index. AB - INTRODUCTION: Early onset pediatric obesity has become a major health concern in the United States. A key contributing factor to early onset childhood is socialization to the eating and mealtime environment. Maternal feeding styles play an integral role in how children are socialized to the eating and mealtime environment. METHOD: The study utilized a descriptive correlational research design. The sample was 126 mother/child dyads recruited from a southeastern Michigan Head Start program. Each mother completed a research packet. RESULTS: Results indicated that maternal beliefs such as nutritional belief and belief about the child's eating style were significantly associated with maternal feeding style. Maternal behaviors were associated with maternal feeding styles. DISCUSSION: Overall, the study provides a description of maternal beliefs and behaviors related to the body weight status of a preschool-aged child. PMID- 26833212 TI - Newborn Infant With Epidermolysis Bullosa and Ankyloglossia. PMID- 26833213 TI - Comparative fiber property and transcriptome analyses reveal key genes potentially related to high fiber strength in cotton (Gossypium hirsutum L.) line MD52ne. AB - BACKGROUND: Individual fiber strength is an important quality attribute that greatly influences the strength of the yarn spun from cotton fibers. Fiber strength is usually measured from bundles of fibers due to the difficulty of reliably measuring strength from individual cotton fibers. However, bundle fiber strength (BFS) is not always correlated with yarn strength since it is affected by multiple fiber properties involved in fiber-to-fiber interactions within a bundle in addition to the individual fiber strength. Molecular mechanisms responsible for regulating individual fiber strength remain unknown. Gossypium hirsutum near isogenic lines (NILs), MD52ne and MD90ne showing variations in BFS provide an opportunity for dissecting the regulatory mechanisms involved in individual fiber strength. RESULTS: Comprehensive fiber property analyses of the NILs revealed that the superior bundle strength of MD52ne fibers resulted from high individual fiber strength with minor contributions from greater fiber length. Comparative transcriptome analyses of the NILs showed that the superior bundle strength of MD52ne fibers was potentially related to two signaling pathways: one is ethylene and the interconnected phytohormonal pathways that are involved in cotton fiber elongation, and the other is receptor-like kinases (RLKs) signaling pathways that are involved in maintaining cell wall integrity. Multiple RLKs were differentially expressed in MD52ne fibers and localized in genomic regions encompassing the strength quantitative trait loci (QTLs). Several candidate genes involved in crystalline cellulose assembly were also up-regulated in MD52ne fibers while the secondary cell wall was produced. CONCLUSION: Comparative phenotypic and transcriptomic analyses revealed differential expressions of the genes involved in crystalline cellulose assembly, ethylene and RLK signaling pathways between the MD52ne and MD90ne developing fibers. Ethylene and its phytohormonal network might promote the elongation of MD52ne fibers and indirectly contribute to the bundle strength by potentially improving fiber-to fiber interactions. RLKs that were suggested to mediate a coordination of cell elongation and SCW biosynthesis in other plants might be candidate genes for regulating cotton fiber cell wall assembly and strength. PMID- 26833214 TI - Epidemiology of symptoms of dry eye disease (DED) in Jordan: A cross-sectional non-clinical population-based study. AB - PURPOSE: To describe the prevalence of dry eye disease (DED) symptoms and to identify associated risk factors in a general non-clinical population in Jordan. METHODS: In this cross-sectional study, participants were selected randomly from the general non-clinical population in Jordan. Participants aged 18 years or over completed the Arabic version of Ocular Surface Disease Index (OSDI) questionnaire on dry eye symptoms. RESULTS: The OSDI questionnaire was completed by 1039 subjects (609 female and 430 male). The mean OSDI score for the study population was 27, with 59% of subjects showed OSDI score >=20 (a cut off score for mild DED symptoms). Females showed significantly higher mean OSDI score than males in the older age group (p=0.01). The prevalence of all dryness symptoms was markedly reported in older age group >45 years and contact lens wearers (p<0.05). The most commonly reported DED symptom was sensitivity to light and intense symptoms were markedly reported during windy conditions. Vision-related quality of life was also affected in subjects with dryness symptoms. Working with computers and ATM was among those that highly affected. CONCLUSION: The results show that symptoms of dry eye were prevalent in this non-clinical population. Contact lenses wear and older age were found to be associated with dry eye symptoms. PMID- 26833215 TI - Therapeutic Strategies for the Treatment of Severe Cushing's Syndrome. AB - Severe Cushing's syndrome presents an acute emergency and is defined by massively elevated random serum cortisol [more than 36 MUg/dL (1000 nmol/L)] at any time or a 24-h urinary free cortisol more than fourfold the upper limit of normal and/or severe hypokalaemia (<3.0 mmol/L), along with the recent onset of one or more of the following: sepsis, opportunistic infection, intractable hypokalaemia, uncontrolled hypertension, heart failure, gastrointestinal haemorrhage, glucocorticoid-induced acute psychosis, progressive debilitating myopathy, thromboembolism or uncontrolled hyperglycaemia and ketocacidosis. Treatment focuses on the management of the severe metabolic disturbances followed by rapid resolution of the hypercortisolaemia, and subsequent confirmation of the cause. Emergency lowering of the elevated serum cortisol is most rapidly achieved with oral metyrapone and/or ketoconazole; if parenteral therapy is required then intravenous etomidate is rapidly effective in almost all cases, but all measures require careful supervision. The optimal order and combination of drugs to treat severe hypercortisolaemia-mostly in the context of ectopic ACTH-secreting syndrome, adrenocortical carcinoma or an ACTH-secreting pituitary adenoma (mainly macroadenomas)-is not yet established. Combination therapy may be useful not only to rapidly control cortisol excess but also to lower individual drug dosages and consequently the possibility of adverse effects. If medical treatments fail, bilateral adrenalectomy should be performed in the shortest possible time span to prevent the debilitating complications of uncontrolled hypercortisolaemia. PMID- 26833216 TI - Abductor pollicis longus tendon interposition for arthrosis of the first carpo metacarpal joint. Long-term results. AB - BACKGROUND: We performed an interposition arthroplasty using the abductor pollicis longus tendon for arthrosis in the basal joint of the thumb that needed surgery from 1995 to 2010. In 2001 47 patients (55 thumbs) were reviewed after 3.5 (1-5) years. The pain relief was excellent in 32 thumbs, and 25 patients improved their ability to perform daily tasks. Mobility was well preserved. Key pinch and grip strengths averaged 78% and 89%, respectively, of those in unaffected hands. We have now re-examined all 33 available patients (36 thumbs) 11-14 years after surgery. METHODS: Fourty one of the originally examined patients were still alive. Seven were too ill to attend a follow-up and one refused. The remainder were examined in a fashion as similar as possible to that at the original review. The patients' subjective estimations of pain during the last week and satisfaction with the cosmetic and general results were recorded on visual analogue scales. The patients' ability to perform various activities of daily living were recorded and they completed the Disability of the arm, shoulder and hand (DASH) questionnaire. The mobility of the wrist and abduction of the thumb of the operated hands were recorded with a goniometer. Grip and pinch strength were measured and new radiographs were obtained. RESULTS: Key pinch strength had increased significantly over the last 10 years. The mobility was still good, except for thumb abduction, which had decreased with time. The median DASH score had fallen from 28 to 20 between the two reviews. There was insignificant further median loss of distance between the scaphoid and the metacarpal since the earlier review. CONCLUSIONS: The good results of this procedure found soon after surgery are maintained long-term. PMID- 26833217 TI - The dual specificity phosphatase 2 gene is hypermethylated in human cancer and regulated by epigenetic mechanisms. AB - BACKGROUND: Dual specificity phosphatases are a class of tumor-associated proteins involved in the negative regulation of the MAP kinase pathway. Downregulation of the dual specificity phosphatase 2 (DUSP2) has been reported in cancer. Epigenetic silencing of tumor suppressor genes by abnormal promoter methylation is a frequent mechanism in oncogenesis. It has been shown that the epigenetic factor CTCF is involved in the regulation of tumor suppressor genes. METHODS: We analyzed the promoter hypermethylation of DUSP2 in human cancer, including primary Merkel cell carcinoma by bisulfite restriction analysis and pyrosequencing. Moreover we analyzed the impact of a DNA methyltransferase inhibitor (5-Aza-dC) and CTCF on the epigenetic regulation of DUSP2 by qRT-PCR, promoter assay, chromatin immuno-precipitation and methylation analysis. RESULTS: Here we report a significant tumor-specific hypermethylation of DUSP2 in primary Merkel cell carcinoma (p = 0.05). An increase in methylation of DUSP2 was also found in 17 out of 24 (71%) cancer cell lines, including skin and lung cancer. Treatment of cancer cells with 5-Aza-dC induced DUSP2 expression by its promoter demethylation, Additionally we observed that CTCF induces DUSP2 expression in cell lines that exhibit silencing of DUSP2. This reactivation was accompanied by increased CTCF binding and demethylation of the DUSP2 promoter. CONCLUSIONS: Our data show that aberrant epigenetic inactivation of DUSP2 occurs in carcinogenesis and that CTCF is involved in the epigenetic regulation of DUSP2 expression. PMID- 26833218 TI - Transverse Compression of Tendons. AB - A study was made of the deformation of tendons when compressed transverse to the fiber-aligned axis. Bovine digital extensor tendons were compression tested between flat rigid plates. The methods included: in situ image-based measurement of tendon cross-sectional shapes, after preconditioning but immediately prior to testing; multiple constant-load creep/recovery tests applied to each tendon at increasing loads; and measurements of the resulting tendon displacements in both transverse directions. In these tests, friction resisted axial stretch of the tendon during compression, giving approximately plane-strain conditions. This, together with the assumption of a form of anisotropic hyperelastic constitutive model proposed previously for tendon, justified modeling the isochronal response of tendon as that of an isotropic, slightly compressible, neo-Hookean solid. Inverse analysis, using finite-element (FE) simulations of the experiments and 10 s isochronal creep displacement data, gave values for Young's modulus and Poisson's ratio of this solid of 0.31 MPa and 0.49, respectively, for an idealized tendon shape and averaged data for all the tendons and E = 0.14 and 0.10 MPa for two specific tendons using their actual measured geometry. The compression load versus displacement curves, as measured and as simulated, showed varying degrees of stiffening with increasing load. This can be attributed mostly to geometrical changes in tendon cross section under load, varying according to the initial 3D shape of the tendon. PMID- 26833219 TI - Evaluating validity of various acupuncture device types: a random sequence clinical trial. AB - BACKGROUND: Although various placebo acupuncture devices have been developed and used in acupuncture research, there is controversy concerning whether these devices really serve as appropriate placebos for control groups. METHODS/DESIGN: The proposed study is a single-center prospective random sequence participant- and assessor-blinded trial with two parallel arms. A total of 76 participants will be randomly assigned to Group 1 or Group 2 in a 1:1 ratio. Group 1 will consist of Sham Streitberger's needle, Real Streitberger's needle, and Phantom acupuncture session. Group 2 will consist of Park Sham device with real needle, Park Sham device with sham needle, and no treatment session. Participants will have a total of three acupuncture sessions in a day. The primary endpoint is blinding test questionnaire 1. Secondary endpoints are the Bang's blinding index, the Massachusetts General Hospital Acupuncture Sensation Scale index, and physiological data including heart rate, heart rate variability, and skin conductance response. DISCUSSION: This trial will evaluate the relevance of using placebo acupuncture devices as controls using a validation test procedure. TRIAL REGISTRATION: Clinical Research Information Service: KCT0001347 . PMID- 26833220 TI - Factors Associated with Primary Headache According to Diagnosis, Sex, and Social Group. AB - BACKGROUND: We previously showed that migraine and tension-type headache (TTH) have a high prevalence that differs markedly between social groups. Here, we aim to identify factors associated with migraine and TTH (possible risk factors) in three social groups to better understand the difference in prevalence between sexes, between different headache diagnoses, and between different social groups. MATERIAL AND METHODS: The study included 3124 persons: 1007 blood donors (484 females, mean age 34.1), 1075 workers in an oil and gas factory (146 females, mean age 40.4), and 1042 medical students (719 females, mean age 20.6). Headache diagnoses and associated factors were identified by direct or telephone interview using a semistructured, validated form. It was administered by a neurologist or by specially trained senior medical students under supervision of a neurologist. RESULTS: We report factors associated with headache according to diagnosis, sex, and social group using multivariate logistic regression analysis. (1) According to diagnosis. Many associated factors were common for migraine and TTH: female sex, arterial hypertension, history of head trauma, and consumption of light alcoholic beverages. To be a student was associated with the highest risk of migraine (OR 6.6; 95% CI 4.2-10.4) and TTH (OR 3.6; 95% SI 2.7-4.8). Low physical activity (OR 1.6; 95% CI 1.0-2.4) and family history of headache (OR 2.1; 95% CI 1.5-2.9) were associated only with migraine. Current smoking and BMI > 25 were negatively associated with migraine and TTH. (2) According to sex. Common factors associated with migraine and TTH in both sexes included history of head trauma, family history of headache, and arterial hypertension. Use of alcohol was different between sexes: in males consumption of strong alcoholic beverages was associated with TTH (OR 1.5; 95% CI 1.0-2.0) and in females consumption of light alcoholic beverages was associated with migraine (OR 3.49; 2.03-6.02) and TTH (OR 3.0; 95% CI 1.93-4.66). Low physical activity was associated with migraine in females (OR 1.9; 95% CI 1.1-3.2). (3) According to social group. Common factors associated with headache in all groups included female sex, family history of headache, history of head trauma, and arterial hypertension. Consumption of light alcoholic beverages was associated with migraine and TTH in blood donors and students. Only two factors were specific to a social group: consumption of strong alcoholic beverages was associated with TTH in blood donors (OR 1.5; 95% CI 1.1 2.1), low physical activity was associated with migraine in students (OR 1.98; 95% CI 1.04-3.74) and with TTH in workers (OR 2.1; 95% CI 1.2-3.7). CONCLUSION: Most of the associated factors were shared by the sexes. The associated factors varied somewhat more between migraine and TTH and between social groups. To be a student was associated with the highest risk of headache. Factors different from those in the present and previous studies should be studied in the future in order to better understand the differences in associated factors according to diagnosis, sex, and social group. PMID- 26833222 TI - RAG2 and XLF/Cernunnos interplay reveals a novel role for the RAG complex in DNA repair. AB - XRCC4-like factor (XLF) functions in classical non-homologous end-joining (cNHEJ) but is dispensable for the repair of DNA double-strand breaks (DSBs) generated during V(D)J recombination. A long-standing hypothesis proposes that, in addition to its canonical nuclease activity, the RAG1/2 proteins participate in the DNA repair phase of V(D)J recombination. Here we show that in the context of RAG2 lacking the C-terminus domain (Rag2(c/c) mice), XLF deficiency leads to a profound lymphopenia associated with a severe defect in V(D)J recombination and, in the absence of p53, increased genomic instability at V(D)J sites. In addition, Rag2(c/c) XLF(-/-) p53(-/-) mice develop aggressive pro-B cell lymphomas bearing complex chromosomal translocations and gene amplifications involving Igh and c myc/pvt1 loci. Our results reveal an unanticipated functional interplay between the RAG complex and XLF in repairing RAG-induced DSBs and maintaining genome integrity during antigen receptor gene assembly. PMID- 26833224 TI - Recent Advances and Applications in Synchrotron X-Ray Protein Footprinting for Protein Structure and Dynamics Elucidation. AB - Synchrotron X-ray Footprinting is a powerful in situ hydroxyl radical labeling method for analysis of protein structure, interactions, folding and conformation change in solution. In this method, water is ionized by high flux density broad band synchrotron X-rays to produce a steady-state concentration of hydroxyl radicals, which then react with solvent accessible side-chains. The resulting stable modification products are analyzed by liquid chromatography coupled to mass spectrometry. A comparative reactivity rate between known and unknown states of a protein provides local as well as global information on structural changes, which is then used to develop structural models for protein function and dynamics. In this review we describe the XF-MS method, its unique capabilities and its recent technical advances at the Advanced Light Source. We provide a comparison of other hydroxyl radical and mass spectrometry based methods with XFMS. We also discuss some of the latest developments in its usage for studying bound water, transmembrane proteins and photosynthetic protein components, and the synergy of the method with other synchrotron based structural biology methods. PMID- 26833223 TI - Neural correlates of working memory training in HIV patients: study protocol for a randomized controlled trial. AB - BACKGROUND: Potent combined antiretroviral therapy decreased the incidence and severity of HIV-associated neurocognitive disorders (HAND); however, no specific effective pharmacotherapy exists for HAND. Patients with HIV commonly have deficits in working memory and attention, which may negatively impact many other cognitive domains, leading to HAND. Since HAND may lead to loss of independence in activities of daily living and negative emotional well-being, and incur a high economic burden, effective treatments for HAND are urgently needed. This study aims to determine whether adaptive working memory training might improve cognitive functions and neural network efficiency and possibly decrease neuroinflammation. This study also aims to assess whether subjects with the LMX1A rs4657412 TT(AA) genotype show greater training effects from working memory training than TC(AG) or CC(GG)-carriers. METHODS/DESIGN: 60 HIV-infected and 60 seronegative control participants will be randomized to a double-blind active controlled study, using adaptive versus non-adaptive Cogmed Working Memory Training(r) (CWMT), 20-25 sessions over 5-8 weeks. Each subject will be assessed with near- and far-transfer cognitive tasks, self-reported mood and executive function questionnaires, and blood-oxygenation level-dependent functional MRI during working memory (n-back) and visual attention (ball tracking) tasks, at baseline, 1-month, and 6-months after CWMT. Furthermore, genotyping for LMX1A rs4657412 will be performed to identify whether subjects with the TT(AA)-genotype show greater gain or neural efficiency after CWMT than those with other genotypes. Lastly, cerebrospinal fluid will be obtained before and after CWMT to explore changes in levels of inflammatory proteins (cytokines and chemokines) and monoamines. DISCUSSION: Improving working memory in HIV patients, using CWMT, might slow the progression or delay the onset of HAND. Observation of decreased brain activation or normalized neural networks, using fMRI, after CWMT would lead to a better understanding of how neural networks are modulated by CWMT. Moreover, validating the greater training gain in subjects with the LMX1A-TT(AA) genotype could lead to a personalized approach for future working memory training studies. Demonstrating and understanding the neural correlates of the efficacy of CWMT in HIV patients could lead to a safe adjunctive therapy for HAND, and possibly other brain disorders. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02602418. PMID- 26833225 TI - An accelerated hypofractionated schedule with a daily concomitant boost after breast conservation surgery: the feasibility and toxicity. AB - AIMS AND BACKGROUND: Reduction of overall treatment time of postoperative irradiation and evaluation of the feasibility and preliminary toxicity of an accelerated hypofractionated whole breast irradiation with an addition of a concomitant daily boost in patients with early breast cancer submitted to conservation surgery. MATERIALS: Between June 2010 and September 2011, 122 patients underwent accelerated hypofractionated adjuvant radiation after conservation surgery (pT1 or pT2, pN0-N1). Radiotherapy consisted of 45 Gy, to the whole breast in 20 fractions with 2.25 Gy/fraction; an additional daily boost dose of 0.25 Gy was concomitantly delivered to the lumpectomy cavity, total dose 5Gy. Toxicity was assessed at the end of radiation therapy and at 3, 6, and 12 months using the RTOG/EORTC toxicity scale. Cosmetic results were assessed in agreement with the Harvard criteria. RESULTS: Median follow-up was 31 months, 74% showed grade 0-1 skin toxicity, 20% grade 2, and 6% grade 3. At 3 months of follow-up, grade 0 skin toxicity was observed in 51% of cases; grade 1 in 36%, and grade 2 in 13%. At 6 months, late skin and subcutaneous tissue toxicities were scored as grade 0 in 71%, grade 1 in 18%, and grade 2 in 11% of patients. At 1 year almost all the patients showed grade 0-1 skin toxicity. 97% of patients showed excellent or good cosmetic results. CONCLUSIONS: Accelerated hypofractionated radiotherapy for early breast cancer with concomitant electron boost seems to be feasible providing consistent clinical results with acceptable toxicity profile. PMID- 26833226 TI - Determining the order of resistance genes against Stagonospora nodorum blotch, Fusarium head blight and stem rust on wheat chromosome arm 3BS. AB - BACKGROUND: Stagonospora nodorum blotch (SNB), Fusarium head blight (FHB) and stem rust (SR), caused by the fungi Parastagonospora (synonym Stagonospora) nodorum, Fusarium graminearum and Puccinia graminis, respectively, significantly reduce yield and quality of wheat. Three resistance factors, QSng.sfr-3BS, Fhb1 and Sr2, conferring resistance, respectively, to SNB, FHB and SR, each from a unique donor line, were mapped previously to the short arm of wheat chromosome 3B. Based on published reports, our hypothesis was that Sr2 is the most distal, Fhb1 the most proximal and QSng.sfr-3BS is in between Sr2 and Fhb1 on wheat chromosome arm 3BS. RESULTS: To test this hypothesis, 1600 F2 plants from crosses between parental lines Arina, Alsen and Ocoroni86, conferring resistance genes QSng.sfr-3BS, Fhb1 and Sr2, respectively, were genotyped and phenotyped for SNB along with the parental lines. Five closely linked single-nucleotide polymorphism (SNP) markers were used to make the genetic map and determine the gene order. CONCLUSIONS: The results indicate that QSng.sfr-3BS is located between the other two resistance genes on chromosome 3BS. Knowing the positional order of these resistance genes will aid in developing a wheat line with all three genes in coupling, which has the potential to provide broad-spectrum resistance preventing grain yield and quality losses. PMID- 26833227 TI - Patterns of pseudophakic retinal detachment in a referral tertiary care center and the need for improving cataract surgical training. AB - PURPOSE: To determine the risk factors associated with development of rhegmatogenous retinal detachment (RRD) in patients undergoing different types of cataract surgery. METHODS: Records of 200 patients presenting with pseudophakic retinal detachment (PRD) between January 2012 and July 2013 at a tertiary care center were reviewed. Duration and type of cataract surgery (phacoemulsification, extracapsular cataract extraction [ECCE], and small-incision cataract surgery [SICS]) and history of YAG capsulotomy with risk factors were recorded. Presence or absence of these risk factors was analyzed and their association with type of cataract surgery was evaluated. RESULTS: Of these 200 patients, 137 were male and 63 were female. The mean age of the patients was 55.19 +/- 12.60 years and mean duration of cataract surgery to diagnosis of RRD was 8.64 +/- 5.15 months. Most patients underwent phacoemulsification (45%), followed by ECCE (31.5%) and SICS (23.5%). Most of the patients with PRD had complicated cataract surgery with intraocular lens (IOL) in sulcus in 63%, anterior chamber IOL in 3%, and aphakia in 0.5%. There was no difference among the 3 types of surgery performed in mean presenting visual acuity, duration between cataract surgery and YAG capsulotomy, or number of posterior chamber IOLs. Incidence of posterior capsular rent (p = 0.02) and presence of vitreous in anterior chamber (p = 0.01) were significantly higher for patients with retinal detachment (RD) who underwent SICS. CONCLUSIONS: Many risk factors are associated with RD development after cataract surgery. More stringent efforts at improving the quality of cataract surgical training are likely to help in reducing the risk of PRD. PMID- 26833228 TI - Authors' reply to comments to: Anterior segment morphologic changes related to alpha-1 adrenergic receptor antagonists use. PMID- 26833229 TI - Y-split recession vs isolated recession of the lateral rectus muscle in the treatment of vertical shooting in exotropic Duane retraction syndrome. AB - PURPOSE: To compare the results of 2 surgical procedures in the management of vertical shooting in exotropic Duane retraction syndrome (XT-DRS). METHODS: This was a prospective, interventional study of consecutive patients with XT-DRS with vertical shooting on adduction operated on from August 2012 to January 2015. A total of 25 patients were identified and were divided into 2 groups: the Y-split (Y) group, which included 12 patients, who underwent Y-splitting with recession of the lateral rectus muscle (LR); and the isolated recession (R) group, which included 13 patients, who underwent isolated LR recession. Surgical outcomes in both groups were compared in terms of improvements in vertical shoots, ocular deviation, and face turn. RESULTS: Upshoot, downshoot, XT, and face turn showed significant postoperative improvement in both groups (p<0.001). When comparing the groups, the difference in the average correction of the upshoot and downshoot was statistically significant (p = 0.0004 and 0.0174, respectively) in benefit of the Y-group. One case of horizontal overcorrection (consecutive esotropia) with another case of horizontal undercorrection (persistent XT) were reported postoperatively in the Y-group. CONCLUSIONS: In our series, both procedures achieved comparable results in the correction of XT and face turn. The combined Y split recession procedure attained a more significant improvement of upshoot and downshoot but with higher incidence of postoperative complications. PMID- 26833230 TI - Multiorganism, drug-resistant keratitis treated by corneal crosslinking. AB - PURPOSE: To describe a case of multiorganism, drug-resistant keratitis that responded well to corneal crosslinking (CXL) treatment. METHODS: A 52-year-old man presented to our institute with a 2-month ocular history of infectious keratitis in his right eye, on topical antibacterial, antifungal, and antiprotozoan treatment, and complained of increase in pain, discomfort, and visual deterioration. Slit-lamp examination revealed advanced infectious keratitis (extensive deep corneal infiltrate with perineuritis). Cultural and molecular analysis of obtained corneal specimens demonstrated combined fungal and Acanthamoeba infection; confocal microscopy confirmed Acanthamoeba infection. Intense targeted topical antifungal and antiprotozoan treatment was initiated immediately and 1 month later CXL was performed due to drug resistance of the infection. RESULTS: Two weeks after CXL treatment, the corneal findings had deteriorated, while a corneal abscess was formed and extended at almost half of the cornea. This was gradually limited and the corneal infiltrate and abscess were eventually decreased. In addition, the symptoms improved. CONCLUSIONS: Corneal crosslinking could be an effective therapy in the management of advanced infectious keratitis unresponsive to conventional medical treatment. PMID- 26833231 TI - Evaluation of anterior segment parameters in patients with neurofibromatosis type 1. AB - PURPOSE: To evaluate anterior segment parameters in patients with neurofibromatosis type 1 (NF1) in comparison to healthy individuals. METHODS: A total of 34 eyes from 17 patients with NF1 and 34 eyes from 17 age- and sex matched healthy individuals were included in this study. Each participant underwent a comprehensive ophthalmic assessment including best-corrected visual acuity, slit-lamp biomicroscopy, stereoscopic fundus examination, and intraocular pressure. Central corneal thickness, corneal volume, corneal curvatures (K1 and K2), anterior chamber depth, anterior chamber volume, iridocorneal angle, and pupil size values were measured by Pentacam Scheimpflug camera. RESULTS: The mean anterior chamber depth, iridocorneal angle, and anterior chamber volume measurements revealed significantly lower values when compared with the control group (p<0.001, p<0.001, and p = 0.041, respectively). However, the mean pupil size was significantly larger when compared with the control group (p = 0.008). Central corneal thickness, corneal volume, K1, and K2 values were similar between the study and control groups (p = 0.875, p = 0.549, p = 0.066, and p = 0.166, respectively). CONCLUSIONS: Our results reveal that NF1 is associated with statistically significant alterations in anterior chamber depth, iridocorneal angle, anterior chamber volume, and pupil size in patients with NF1 when compared with healthy controls. PMID- 26833232 TI - Patient perceptions and experiences of stereotactic radiotherapy for wet age related macular degeneration. AB - PURPOSE: Wet age-related macular degeneration (ARMD) is a leading cause of visual impairment. Anti-vascular endothelial growth factor (VEGF) injections are the mainstay of treatment but require monthly injections and frequent hospital visits. A novel approach to treatment with the use of stereotactic radiotherapy (Oraya IRay) as an adjunct to ranibizumab injections has shown promising results. We explored patients' experiences of receiving Oraya therapy for wet ARMD. METHODS: We present a consecutive case series with objective and detailed reporting of the personal experiences of 5 patients with active wet ARMD treated with Oraya radiotherapy in our unit. We provided all patients who had received one Oraya treatment with a standardized survey composed of 10 questions addressing the experience of receiving this treatment. RESULTS: Generally, patients reported positive experiences of receiving Oraya treatment and perceived this treatment as a better option in comparison with anti-VEGF injections. However, the patients' perceptions of Oraya treatment varied according to patients' previous experiences of anti-VEGF injections and expectations of treatment. CONCLUSIONS: Patients mainly justified their decision to receive Oraya treatment by expecting fewer intravitreal injections, but more research on this topic is needed to suggest new evidence-based treatment protocols for patients with wet ARMD. PMID- 26833233 TI - Pupil response to tropicamide following corneal crosslinking. AB - PURPOSE: To evaluate the effect of corneal crosslinking (CXL) with ultraviolet A (UVA) irradiation on pupil response to tropicamide 0.5% instillation. METHODS: This prospective interventional study enrolled 17 patients (19 eyes) with progressive keratoconus who underwent CXL with UVA irradiation. Central corneal thickness (CCT) was evaluated with the use of anterior segment optical coherence tomography (Visante OCT 3.0). Pupil diameter was measured with the use of Colvard infrared pupillometer before the instillation of tropicamide 0.5% and after the instillation of tropicamide every 5 minutes for total duration of 30 minutes. Corneal epithelial integrity was examined with the use of fluorescein dye staining. Measurements were performed 1 day preoperatively and 1 month postoperatively, with emphasis on simulating the same light conditions regarding the pupil measurements. RESULTS: No intraoperative or postoperative complications were observed in any of the patients. Mean CCT decreased significantly (p<0.001) 1 month postoperatively. Mean postoperative pupil size did not change significantly at any time point compared to the mean preoperative measurements. CONCLUSIONS: The CXL procedure seems not to impair effectiveness of topical drugs, using pupil size measurements after tropicamide 0.5% instillation. PMID- 26833234 TI - Surgical management of traumatic nasolacrimal duct obstruction. AB - PURPOSE: To evaluate etiologies, demographics, and surgical outcomes in cases of traumatic nasolacrimal duct obstruction (NLDO). METHODS: Charts of 35 patients with the diagnosis of traumatic NLDO were reviewed retrospectively. Patient demographics, type of trauma, previous lacrimal surgery history, surgical treatment, follow-up time, and anatomical and functional outcomes were evaluated. RESULTS: Forty eyes of 35 patients were included in this study over 12 years. Twenty-four patients were male (68.5%) and the mean age of the patients was 31.52 +/- 14.58 years (range 9-68). The most common etiology was motor vehicle accidents (52.5%), followed by high velocity blunt injury (27.5%), accidental fall (7.5%), occupational trauma (5%), iatrogenic surgical trauma (5%), and animal bite (2.5%). A total of 21 eyes (52.5%) were treated with external dacryocystorhinostomy (DCR), 30% with conjunctival DCR, 15% with endoscopic DCR, and 2.5% with diode laser-assisted DCR. Mean follow-up time was 23.02 +/- 13.53 months. Functional and anatomical success was recorded in 37 out of 40 eyes (92.5%). CONCLUSIONS: Naso-orbitoethmoidal fracture is the main etiology of traumatic NLDO. The majority of the injuries occurred in male participants from motor vehicle accidents and high-velocity blunt injury. Dacryocystorhinostomy provides anatomical and functional success in 92.5% of cases of traumatic NLDO. PMID- 26833235 TI - Managing the open abdomen: negative pressure closure versus mesh-mediated fascial traction closure: a randomized trial. AB - PURPOSE: To compare the effectiveness of abdominal wall closure using the vacuum assisted closure (NPC) as described by Barker et al. with an institutional protocol using a double polyvinyl bag in the first surgery, which is changed in subsequent surgeries to a polyvinyl bag placed over the bowel loops and a prolene mesh attached to the abdominal fascia (MMFC). METHODS: Randomized controlled trial. Patients with open abdomen (OA) due to a traumatic or a medical cause were included in the study. Variables studied included demographics, indication for surgery, number of interventions, hospital length of stay (HLOS), ICU length of stay, abdominal wound care costs, complication rates, and method and time to definitive fascial closure. RESULTS: From June 2011 to April 2013, 75 patients were enrolled in the study. Patients who died within 48 h were excluded; therefore, 53 patients in total were assessed. NPC achieved fascial closure in 75% of patients, and MMFC achieved closure in 71.9% of patients. The closure rates in patients with OA secondary to medical causes (80% by NPC vs. 71.4% by MMFC) or traumatic causes (70% by NPC vs. 73.7% by MMFC) were similar in both treatment groups. There were no differences between the groups with respect to cause of OA, complications, length of hospital stay, or the length of stay in the intensive care unit. CONCLUSION: MMFC is a method comparable to NPC for the temporary management of OA that results in similar closure and complication rates. PMID- 26833237 TI - Visual Color-Switch Electrochemiluminescence Biosensing of Cancer Cell Based on Multichannel Bipolar Electrode Chip. AB - In this work, we developed a visual electrochemiluminescence (ECL) sensing platform based on a dual-bipolar electrode (D-BPE) array chip. The chip was composed of two arrays of BPEs and three separated arrays of reservoirs filled with buffer, Ru(bpy)3(2+)-TPrA and luminol solutions, respectively. Both BPEs served as ECL reporting platforms. By applying 6.0 V voltage, an array of orange electrochemiluminescence (ECL) signals belonging to Ru(bpy)3(2+) turned on. After adding DNAzyme and H2O2 in Ru(bpy)3(2+) and luminol reservoirs, the orange Ru(bpy)3(2+) signals decreased until vanished due to the quenching effect; meanwhile, a new array of blue ECL signals turned on because of the luminol-H2O2 ECL reaction. The designed D-BPE owns superior properties compared with the three electrode system benefiting from the quantitative relation of bipolar systems, which greatly enhanced the ECL detection sensitivity. Meanwhile, the visual color switch ECL and the ratiometric detecting principle made the results easier to evaluate and more accurate. Quantitative detection of HL-60 cancer cells from 320 cells/mL to 2.5 * 10(5) cells/mL with two linear ranges was achieved. The detection limit was down to 80 cells/mL. Finally, this D-BPE chip could distinguish the tumor cells from normal cells and provide a prospect for cancer diagnosis in a high-throughput, visual way. PMID- 26833238 TI - Is integrating sickle cell disease and HIV screening logical? PMID- 26833239 TI - Burden of sickle cell trait and disease in the Uganda Sickle Surveillance Study (US3): a cross-sectional study. AB - BACKGROUND: Sickle cell disease contributes substantially to mortality in children younger than 5 years in sub-Saharan Africa. In Uganda, 20,000 babies per year are thought to be born with sickle cell disease, but accurate data are not available. We did the cross-sectional Uganda Sickle Surveillance Study to assess the burden of disease. METHODS: The primary objective of the study was to calculate prevalence of sickle cell trait and disease. We obtained punch samples from dried blood spots routinely collected from HIV-exposed infants in ten regions and 112 districts across Uganda for the national Early Infant Diagnosis programme. Haemoglobin electrophoresis by isoelectric focusing was done on all samples to identify those from babies with sickle trait or disease. FINDINGS: Between February, 2014, and March, 2015, 99,243 dried blood spots were analysed and results were available for 97,631. The overall number of children with sickle cell trait was 12,979 (13.3%) and with disease was 716 (0.7%). Sickle cell numbers ranged from 631 (4.6%) for trait and 23 (0.2%) for disease of 13,649 in the South Western region to 1306 (19.8%) for trait and 96 (1.5%) for disease of 6581 in the East Central region. Sickle cell trait was seen in all districts. The lowest prevalence was less than 3.0% in two districts. Eight districts had prevalence greater than 20.0%, with the highest being 23.9%. Sickle cell disease was less common in children older than 12 months or who were HIV positive, which is consistent with comorbidity and early mortality. INTERPRETATION: Prevalence of sickle cell trait and disease were high in Uganda, with notable variation between regions and districts. The data will help to inform national strategies for sickle cell disease, including neonatal screening. FUNDING: Cincinnati Children's Research Foundation. PMID- 26833240 TI - Radical-mediated dehydrogenation of bile acids by means of hydrogen atom transfer to triplet carbonyls. AB - The aim of the present paper is to explore the potential of radical-mediated dehydrogenation of bile salts (BSs), which is reminiscent of the enzymatic action of hydroxysteroid dehydrogenase enzymes (HSDH). The concept has been demonstrated using triplet carbonyls that can be efficiently generated upon selective UVA excitation. Hydrogen atom transfer (HAT) from BSs to triplet benzophenone (BP) derivatives gave rise to radicals, ultimately leading to reduction of the BP chromophore with concomitant formation of the oxo-analogs of the corresponding BSs. The direct reactivity of triplet BP with BSs in the initial step was evaluated by determining the kinetic rate constants using laser flash photolysis (LFP). The BP triplet decay was monitored (lambdamax = 520 nm) upon addition of increasing BS concentrations, and the obtained rate constant values indicated a reactivity of the methine hydrogen atoms in the order of C-3 < C-12 < C-7. The steady-state kinetics of the overall process, monitored through the disappearance of the typical BP absorption band at 260 nm, was much faster under N2 than under O2, also supporting the role of the oxygen-quenchable triplet in the dehydrogenation process. Furthermore, irradiation of deaerated aqueous solutions of sodium cholate in the presence of KPMe provided the oxo-analogs, 3[O],7[O]-CA, 3[O]-CA and 7[O]-CA, arising from the HAT process. PMID- 26833241 TI - Using national movement databases to help inform responses to swine disease outbreaks in Scotland: the impact of uncertainty around incursion time. AB - Modelling is an important component of contingency planning and control of disease outbreaks. Dynamic network models are considered more useful than static models because they capture important dynamic patterns of farm behaviour as evidenced through animal movements. This study evaluates the usefulness of a dynamic network model of swine fever to predict pre-detection spread via movements of pigs, when there may be considerable uncertainty surrounding the time of incursion of infection. It explores the utility and limitations of animal movement data to inform such models and as such, provides some insight into the impact of improving traceability through real-time animal movement reporting and the use of electronic animal movement databases. The study concludes that the type of premises and uncertainty of the time of disease incursion will affect model accuracy and highlights the need for improvements in these areas. PMID- 26833236 TI - Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria. AB - Malaria accounts for an enormous burden of disease globally, with Plasmodium falciparum accounting for the majority of malaria, and P. vivax being a second important cause, especially in Asia, the Americas and the Pacific. During infection with Plasmodium spp., the merozoite form of the parasite invades red blood cells and replicates inside them. It is during the blood-stage of infection that malaria disease occurs and, therefore, understanding merozoite invasion, host immune responses to merozoite surface antigens, and targeting merozoite surface proteins and invasion ligands by novel vaccines and therapeutics have been important areas of research. Merozoite invasion involves multiple interactions and events, and substantial processing of merozoite surface proteins occurs before, during and after invasion. The merozoite surface is highly complex, presenting a multitude of antigens to the immune system. This complexity has proved challenging to our efforts to understand merozoite invasion and malaria immunity, and to developing merozoite antigens as malaria vaccines. In recent years, there has been major progress in this field, and several merozoite surface proteins show strong potential as malaria vaccines. Our current knowledge on this topic is reviewed, highlighting recent advances and research priorities. PMID- 26833242 TI - Metal-based biologically active azoles and beta-lactams derived from sulfa drugs. AB - Metal complexes of Schiff bases derived from sulfamethoxazole (SMZ) and sulfathiazole (STZ), converted to their beta-lactam derivatives have been synthesized and experimentally characterized by elemental analysis, spectral (IR, (1)H NMR, (13)C NMR, and EI-mass), molar conductance measurements and thermal analysis techniques. The structural and electronic properties of the studied molecules were investigated theoretically by performing density functional theory (DFT) to access reliable results to the experimental values. The spectral and thermal analysis reveals that the Schiff bases act as bidentate ligands via the coordination of azomethine nitrogen to metal ions as well as the proton displacement from the phenolic group through the metal ions; therefore, Cu complexes can attain the square planner arrangement and Zn complexes have a distorted tetrahedral structure. The thermogravimetric (TG/DTG) analyses confirm high stability for all complexes followed by thermal decomposition in different steps. In addition, the antibacterial activities of synthesized compounds have been screened in vitro against various pathogenic bacterial species. Inspection of the results revealed that all newly synthesized complexes individually exhibit varying degrees of inhibitory effects on the growth of the tested bacterial species, therefore, they may be considered as drug candidates for bacterial pathogens. The free Schiff base ligands (1-2) exhibited a broad spectrum antibacterial activity against Gram negative Escherichia coli, Pseudomonas aeruginosa, and Proteus spp., and Gram positive Staphylococcus aureus bacterial strains. The results also indicated that the beta-lactam derivatives (3-4) have high antibacterial activities on Gram positive bacteria as well as the metal complexes (5-8), particularly Zn complexes, have a significant activity against all Gram negative bacterial strains. It has been shown that the metal complexes have significantly higher activity than corresponding ligands due to chelation process which reduces the polarity of metal ion by coordinating with ligands. PMID- 26833243 TI - In vitro interactions between anidulafungin and nonsteroidal anti-inflammatory drugs on biofilms of Candida spp. AB - Candida spp. are responsible for many biomaterial-related infections; they give rise to infective pathologies typically associated with biofilm formation. We recently reported that the echinocandin anidulafungin (ANF) showed a strong in vitro activity against both planktonic and biofilms cells. Herein, we report the antifungal activities of ANF alone and in association with some non-steroidal anti-inflammatory drugs (NSAIDs) against nine Candida strain biofilms: four Candida albicans, two Candida glabrata and three Candida guilliermondii. The activity of ANF was assessed using an in vitro microbiological model relevant for clinical practice. ANF proved oneself to be active against biofilms cells, and a clear-cut synergism was found against Candida species biofilms when ANF was used in combination with three NSAIDs: aspirin, diclofenac, ibuprofen. The positive synergism against Candida spp. of ANF in association with aspirin or the other NSAIDs proved to be a very effective antifungal treatment (FICI<0.5). These results may provide the starting point for new combination therapies of ANF with NSAIDs against Candida biofilm pathologies. PMID- 26833244 TI - A clickable psoralen to directly quantify DNA interstrand crosslinking and repair. AB - DNA interstrand crosslinks (ICLs) represent physical obstacles to advancing replication forks and transcription complexes. A range of ICL-inducing agents have successfully been incorporated into cancer therapeutics. While studies have adopted UVA-activated psoralens as model ICL-inducing agents for investigating ICL repair, direct detection of the lesion has often been tempered by tagging the psoralen scaffold with a relatively large reporter group that may perturb the biological activity of the parent psoralen. Here a minimally-modified psoralen probe was prepared featuring a small alkyne handle suitable for click chemistry. The psoralen probe, designated 8-propargyloxypsoralen (8-POP), can be activated by UVA in vitro to generate ICLs that are susceptible to post-labeling with an azide-tagged fluorescent reporter via a copper-catalyzed reaction. A modified alkaline comet assay demonstrated that UVA-activated 8-POP proficiently generated ICLs in cells. Cellular 8-POP-DNA lesions were amenable to click-mediated ligation to fluorescent reporters in situ, which permitted their detection and quantitation by fluorescence microscopy and flow cytometry. Small molecule DNA repair inhibitors to 8-POP-treated cells attenuated the removal of 8-POP-DNA lesions, validating 8-POP as an appropriate probe for investigating cellular ICL repair. The post-labeling strategy applied in this study is inexpensive, rapid and highly modular in nature with the potential for multiple applications in DNA repair studies. PMID- 26833245 TI - Heptapeptide ligands against receptor-binding sites of influenza hemagglutinin toward anti-influenza therapy. AB - The initial attachment of influenza virus to cells is the binding of hemagglutinin (HA) to the sialyloligosaccharide receptor; therefore, the small molecules that inhibit the sugar-protein interaction are promising as HA inhibitors to prevent the infection. We herein demonstrate that sialic acid-mimic heptapeptides are identified through a selection from a primary library against influenza virus HA. In order to obtain lead peptides, an affinity selection from a phage-displayed random heptapeptide library was performed with the HAs of the H1 and H3 strains, and two kinds of the HA-binding peptides were identified. The binding of the peptides to HAs was inhibited in the presence of sialic acid, and plaque assays indicated that the corresponding N-stearoyl peptide strongly inhibited infections by the A/Aichi/2/68 (H3N2) strain of the virus. Alanine scanning of the peptides indicated that arginine and proline were responsible for binding. The affinities of several mutant peptides with single-amino-acid substitutions against H3 HA were determined, and corresponding docking studies were performed. A Spearman analysis revealed a correlation between the affinity of the peptides and the docking study. These results provide a practicable method to design of peptide-based HA inhibitors that are promising as anti-influenza drugs. PMID- 26833247 TI - Comparison of Corneal Biological Healing After Femtosecond LASIK and Small Incision Lenticule Extraction Procedure. AB - PURPOSE: To assess and compare the dry-eye-associated parameters and corneal biomechanical status after small-incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). METHODS: Sixty-five patients' (128 eyes) were collected between November 2012 and April 2013. Thirty five (69 eyes) underwent SMILE and thirty (59 eyes) underwent FS-LASIK. Visual acuity, manifest refraction, tear break-up time (TBUT), Schirmer's test (ST), corneal sensitivity, Ocular Surface Disease Index (OSDI), corneal hysteresis (CH) and corneal resistance factor (CRF) were evaluated preoperatively and 1 day, 1 week, 1 month, 3 and 6 months postoperatively. RESULTS: There was no significant difference in visual outcomes of SMILE and FS-LASIK (p = 0.208). TBUT, ST, CH and CRF decreased significantly after surgery in both groups (all p < 0.05); however, the decrease of TBUT, ST and CRF in the SMILE group was not as significant as that in the FS-LASIK group (all p < 0.05) and the change of CH value was comparable in both groups (p = 0.052).Corneal sensitivity was significantly decreased in the FS-LASIK group postoperatively (p < 0.05), but not significantly changed in the SMILE group (p > 0.05). OSDI scores were significantly increased after surgery for the two groups (all p < 0.05), and the scores were much higher in the FS-LASIK group than in the SMILE group (p = 0.000). CONCLUSION: The corneal biological healing of SMILE surgery was superior to FS-LASIK in the early period. PMID- 26833248 TI - Validation of the ANSR((r)) Listeria monocytogenes Method for Detection of Listeria monocytogenes in Selected Food and Environmental Samples. AB - Work was conducted to validate performance of the ANSR((r)) for Listeria monocytogenes method in selected food and environmental matrixes. This DNA-based assay involves amplification of nucleic acid via an isothermal reaction based on nicking enzyme amplification technology. Following single-step sample enrichment for 16-24 h for most matrixes, the assay is completed in 40 min using only simple instrumentation. When 50 distinct strains of L. monocytogenes were tested for inclusivity, 48 produced positive results, the exceptions being two strains confirmed by PCR to lack the assay target gene. Forty-seven nontarget strains (30 species), including multiple non-monocytogenes Listeria species as well as non Listeria, Gram-positive bacteria, were tested, and all generated negative ANSR assay results. Performance of the ANSR method was compared with that of the U.S. Department of Agriculture, Food Safety and Inspection Service Microbiology Laboratory Guidebook reference culture procedure for detection of L. monocytogenes in hot dogs, pasteurized liquid egg, and sponge samples taken from an inoculated stainless steel surface. In addition, ANSR performance was measured against the U.S. Food and Drug Administration Bacteriological Analytical Manual reference method for detection of L. monocytogenes in Mexican-style cheese, cantaloupe, sprout irrigation water, and guacamole. With the single exception of pasteurized liquid egg at 16 h, ANSR method performance as quantified by the number of positives obtained was not statistically different from that of the reference methods. Robustness trials demonstrated that deliberate introduction of small deviations to the normal assay parameters did not affect ANSR method performance. Results of accelerated stability testing conducted using two manufactured lots of reagents predicts stability at the specified storage temperature of 4 degrees C of more than 1 year. PMID- 26833249 TI - Molecular characterization of human coronaviruses and their circulation dynamics in Kenya, 2009-2012. AB - BACKGROUND: Human Coronaviruses (HCoV) are a common cause of respiratory illnesses and are responsible for considerable morbidity and hospitalization across all age groups especially in individuals with compromised immunity. There are six known species of HCoV: HCoV-229E, HCoV-NL63, HCoV-HKU1, HCoV-OC43, MERS CoV and SARS-HCoV. Although studies have shown evidence of global distribution of HCoVs, there is limited information on their presence and distribution in Kenya. METHODS: HCoV strains that circulated in Kenya were retrospectively diagnosed and molecularly characterized. A total of 417 nasopharyngeal specimens obtained between January 2009 and December 2012 from around Kenya were analyzed by a real time RT-PCR using HCoV-specific primers. HCoV-positive specimens were subsequently inoculated onto monolayers of LL-CMK2 cells. The isolated viruses were characterized by RT-PCR amplification and sequencing of the partial polymerase (pol) gene. RESULTS: The prevalence of HCoV infection was as follows: out of the 417 specimens, 35 (8.4 %) were positive for HCoV, comprising 10 (2.4 %) HCoV-NL63, 12 (2.9 %) HCoV-OC43, 9 (2.1 %) HCoV-HKU1, and 4 (1 %) HCoV-229E. The Kenyan HCoV strains displayed high sequence homology to the prototypes and contemporaneous strains. Evolution analysis showed that the Kenyan HCoV-OC43 and HCoV-NL63 isolates were under purifying selection. Phylogenetic evolutionary analyses confirmed the identities of three HCoV-HKU1, five HCoV-NL63, eight HCoV OC43 and three HCoV-229E. CONCLUSIONS: There were yearly variations in the prevalence and circulation patterns of individual HCoVs in Kenya. This paper reports on the first molecular characterization of human Coronaviruses in Kenya, which play an important role in causing acute respiratory infections among children. PMID- 26833250 TI - Identification and team-based interprofessional management of hospitalized vulnerable older adults. AB - BACKGROUND: Extended hospital stays and complications are common among older adults and may lead to morbidity and loss of independence. Specialized geriatric units have been shown to improve outcomes but, with the growing numbers of older adults, may be difficult to scale to meet needs. PURPOSE: The purpose was to evaluate a quality improvement initiative that redesigned unit-based workflow and trained interprofessional teams on general medical/surgical units to create care plans for vulnerable older adults using principles of comprehensive geriatric assessment and team management. METHOD: The evaluation included a cluster randomized controlled trial of 10 medical/surgical units and intention-to-treat analysis of all patients meeting risk screening criteria. RESULTS: N = 1,384, median age = 80.9 years, and 53.5% female. Mean difference in observed vs. expected length of stay was 1.03 days shorter (p = .006); incidence of complications (odds ratio [OR] = 0.45; 95% confidence interval [CI] = 0.21-0.98) and transfer to intensive care (OR = 0.45; 95% CI = 0.25-0.79) lower among patients admitted to intervention units; incidence of discharge to institutional care was higher (OR = 1.43; 95% CI = 1.06-1.93). Mortality during hospitalization (OR = 0.64; 95% CI = 0.37-1.11) did not differ between groups. CONCLUSION: Reorganizing general medical/surgical units to provide team-based interprofessional care can improve outcomes among hospitalized older adults. PMID- 26833252 TI - The undeaning transition: Toward becoming a former dean. AB - Stepping up from leadership is a protracted transition that involves a complex set of interactions with many constituents. It begins with making the personal decision to step up to integrating the role of the dean in existing repertoire of roles that the person enacts. Deliberate planning, awareness of phases, challenges, goals and strategies, clear communication, transparency, and supportive interactions enhance the potential of experiencing a smooth and a healthy transition for the dean who is stepping up, the incoming dean, and the organization. The beginning and the ending of the undeaning transition are not definitive, but indicators of a healthy transition could be identified along the way through disengagement from old roles, focused new interactions, engagement in new roles, redefinition of goals, and narratives and dialogues about topics that reflect a new set of goals. The nature of the role of former dean is developed through careful onboarding strategies for the new dean and interactions with a new set of constituents who perceive the dean as a former dean. There are five phases involved in undeaning. These are the decision, the search, the naming of the new dean, the exit, and reclaiming professorial voice. PMID- 26833251 TI - Using nursing history to inform decision-making: Infectious diseases at the turn of the 20th century. AB - BACKGROUND: This historical paper examines the impact of infectious diseases on the urban poor of Chicago and New York a century ago, before most vaccines were developed. PURPOSE: Working on the front lines of health promotion and health care, nurses and other providers are charged with informing the public about offered vaccines. The intent of this paper is to supplement providers' knowledge about vaccination with an appreciation of the devastation these diseases once caused. METHOD: Historical methodology guided this study in which archival and oral sources were used. DISCUSSION: The continued outbreaks of smallpox at the turn of the twentieth century, when a vaccine was available, may be compared with the re-emergence of measles today. Additionally, this paper shows the devastation caused by other, non-preventable, infections of the period. CONCLUSIONS: Awareness of the history related to the impact of infectious diseases, especially the role nurses played in decision-making related to care, is critical for today's health care providers. PMID- 26833253 TI - Ultrasound examination at term for predicting the outcome of delivery in women with a previous cesarean section. AB - OBJECTIVE: To evaluate if ultrasound variables at term are associated with the mode of delivery in women with previous cesarean section (PCS). METHODS: This was a prospective study of singleton pregnant women who planned a trial of vaginal birth after cesarean delivery. Cervical length, posterior cervical angle, head perineum distance, and estimated fetal weight were measured at 37-39 weeks of gestation. RESULTS: One hundred forty-four pregnancies were examined and vaginal delivery was achieved in 98 women (73%). Logistic regression analysis identified cervical length, head-perineum distance, age, previous vaginal delivery, previous cesarean for dystocia, and Bishop score as predictors of vaginal delivery. Combining ultrasound and clinical parameters, two models for risk scoring that differ in the variable Bishop score or cervical length were constructed. The AUC of these models was 0.867 and 0.855, respectively. CONCLUSIONS: In women with a PCS, measurement of cervical length and head-perineum distance at term is associated with the mode of delivery. A combination of clinical and sonographic parameters at term can predict the likelihood of vaginal delivery. PMID- 26833254 TI - Direct alpha-synuclein promoter transactivation by the tumor suppressor p53. AB - BACKGROUND: Parkinson's disease (PD) is a motor disease associated with the degeneration of dopaminergic neurons of the substantia nigra pars compacta. p53 is a major neuronal pro-apoptotic factor that is at the center of gravity of multiple physiological and pathological cascades, some of which implying several key PD-linked proteins. Since p53 is up-regulated in PD-affected brain, we have examined its ability to regulate the transcription of alpha-synuclein, a key protein that accumulates in PD-related Lewy bodies. RESULTS: We show that pharmacological and genetic up-regulation of p53 expression lead to a strong increase of alpha-synuclein protein, promoter activity and mRNA levels. Several lines of evidence indicate that this transcriptional control is due to the DNA binding properties of p53. Firstly, p53 DNA-binding dead mutations abolish p53 regulation of alpha-synuclein. Secondly, the deletion of p53 responsive element from alpha-synuclein promoter abrogates p53-mediated alpha-synuclein regulation. Thirdly, gel shift and chromatin immunoprecipitation studies indicate that p53 interacts physically with alpha-synuclein promoter both in vitro and in a physiological context. Furthermore, we show that the depletion of endogenous p53 in cells as well as in knockout mice down-regulates alpha-synuclein transcription. CONCLUSIONS: Overall, we have identified alpha-synuclein as a new transcriptional target of p53 and delineated a cellular mechanism feeding the accumulation of toxic aggregated alpha-synuclein in PD. This original alpha-syn regulatory mechanism may be central to PD-related cell death and may lead to novel opportunities to design alternative neuroprotective strategies in PD. PMID- 26833255 TI - An Asymmetric Vinylogous Michael Cascade of Silyl Glyoximide, Vinyl Grignard, and Nitroalkenes via Long Range Stereoinduction. AB - A diastereoselective auxiliary-mediated vinylation/[1,2]-Brook rearrangement/vinylogous Michael cascade of silyl glyoximide, vinylmagnesium bromide, and nitroalkenes is described. The reaction occurs with complete regio- and diastereocontrol in good yield. The diastereoselectivity is induced by a rare instance of 1,7-chirality transfer that is hypothesized to arise from a trans multihetero-decalin transition state. PMID- 26833257 TI - BACE1 Physiological Functions May Limit Its Use as Therapeutic Target for Alzheimer's Disease. AB - The protease beta-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) is required for the production of the amyloid-beta (Abeta) peptide, which is central to the pathogenesis of Alzheimer's disease (AD). Chronic inhibition of this protease may temper amyloid production and cure or prevent AD. However, while BACE1 inhibitors are being pushed forward as drug candidates, a remarkable gap in knowledge on the physiological functions of BACE1 and its close homolog BACE2 becomes apparent. Here we discuss the major discoveries of the past 3 years concerning BACE1 biology and to what extent these could limit the use of BACE1 inhibitors in the clinic. PMID- 26833258 TI - Postsynaptic Neurotransmitter Receptor Reserve Pools for Synaptic Potentiation. AB - At excitatory and inhibitory synapses, an immediate transfer of additional neurotransmitter receptors from non-synaptic positions to the synapse mediates synaptic long-term potentiation (LTP). Different types of non-synaptic reserve pools permit the rapid supply of transmembrane neurotransmitter receptors. Recycling endosomes (REs) serve as an intracellular reservoir of receptors that is delivered to the plasma membrane on LTP induction. Furthermore, AMPA receptors at the non-synaptic plasma membrane provide an extrasynaptic reserve pool that is also important to potentiate synapse function. Finally, bidirectional synaptic versus extrasynaptic trapping of freely diffusing plasma membrane GABAA receptors (GABAARs) by scaffolding proteins modulates synaptic transmission. Here we discuss novel findings regarding neurotransmitter receptor reservoirs and potential reserve pool mechanisms for synaptic potentiation. PMID- 26833259 TI - Metastability and Coherence: Extending the Communication through Coherence Hypothesis Using A Whole-Brain Computational Perspective. AB - Understanding the mechanisms for communication in the brain remains one of the most challenging scientific questions. The communication through coherence (CTC) hypothesis was originally proposed 10 years ago, stating that two groups of neurons communicate most effectively when their excitability fluctuations are coordinated in time (i.e., coherent), and this control by cortical coherence is a fundamental brain mechanism for large-scale, distant communication. In light of new evidence from whole-brain computational modelling of multimodal neuroimaging data, we link CTC to the concept of metastability, which refers to a rich exploration of the functional repertoire made possible by the underlying structural whole-brain connectivity. PMID- 26833256 TI - Cocoa tea (Camellia ptilophylla) water extract inhibits adipocyte differentiation in mouse 3T3-L1 preadipocytes. AB - Cocoa tea (Camellia ptilophylla) is a naturally decaffeinated tea plant. Previously we found that cocoa tea demonstrated a beneficial effect against high fat diet induced obesity, hepatic steatosis, and hyperlipidemia in mice. The present study aimed to investigate the anti-adipogenic effect of cocoa tea in vitro using preadipocytes 3T3-L1. Adipogenic differentiation was confirmed by Oil Red O stain, qPCR and Western blot. Our results demonstrated that cocoa tea significantly inhibited triglyceride accumulation in mature adipocytes in a dose dependent manner. Cocoa tea was shown to suppress the expressions of key adipogenic transcription factors, including peroxisome proliferator-activated receptor gamma (PPAR gamma) and CCAAT/enhancer binding protein (C/EBP alpha). The tea extract was subsequently found to reduce the expressions of adipocyte specific genes such as sterol regulatory element binding transcription factor 1c (SREBP-1c), fatty acid synthase (FAS), Acetyl-CoA carboxylase (ACC), fatty acid translocase (FAT) and stearoylcoenzyme A desaturase-1 (SCD-1). In addition, JNK, ERK and p38 phosphorylation were inhibited during cocoa tea inhibition of 3T3-L1 adipogenic differentiation. Taken together, this is the first study that demonstrates cocoa tea has the capacity to suppress adipogenesis in pre-adipocyte 3T3-L1 similar to traditional green tea. PMID- 26833260 TI - COSMOS: accurate detection of somatic structural variations through asymmetric comparison between tumor and normal samples. AB - An important challenge in cancer genomics is precise detection of structural variations (SVs) by high-throughput short-read sequencing, which is hampered by the high false discovery rates of existing analysis tools. Here, we propose an accurate SV detection method named COSMOS, which compares the statistics of the mapped read pairs in tumor samples with isogenic normal control samples in a distinct asymmetric manner. COSMOS also prioritizes the candidate SVs using strand-specific read-depth information. Performance tests on modeled tumor genomes revealed that COSMOS outperformed existing methods in terms of F-measure. We also applied COSMOS to an experimental mouse cell-based model, in which SVs were induced by genome engineering and gamma-ray irradiation, followed by polymerase chain reaction-based confirmation. The precision of COSMOS was 84.5%, while the next best existing method was 70.4%. Moreover, the sensitivity of COSMOS was the highest, indicating that COSMOS has great potential for cancer genome analysis. PMID- 26833261 TI - Potent in vitro antiviral activity of Cistus incanus extract against HIV and Filoviruses targets viral envelope proteins. AB - Novel therapeutic options are urgently needed to improve global treatment of virus infections. Herbal products with confirmed clinical safety features are attractive starting material for the identification of new antiviral activities. Here we demonstrate that Cistus incanus (Ci) herbal products inhibit human immunodeficiency virus (HIV) infections in vitro. Ci extract inhibited clinical HIV-1 and HIV-2 isolates, and, importantly, a virus isolate with multiple drug resistances, confirming broad anti-HIV activity. Antiviral activity was highly selective for virus particles, preventing primary attachment of the virus to the cell surface and viral envelope proteins from binding to heparin. Bioassay-guided fractionation indicated that Ci extract contains numerous antiviral compounds and therefore has favorably low propensity to induce virus resistance. Indeed, no resistant viruses emerged during 24 weeks of continuous propagation of the virus in the presence of Ci extracts. Finally, Ci extracts also inhibited infection by virus particles pseudotyped with Ebola and Marburg virus envelope proteins, indicating that antiviral activity of Ci extract extends to emerging viral pathogens. These results demonstrate that Ci extracts show potent and broad in vitro antiviral activity against viruses that cause life-threatening diseases in humans and are promising sources of agents that target virus particles. PMID- 26833262 TI - A Novel COL4A4 Mutation Identified in a Chinese Family with Thin Basement Membrane Nephropathy. AB - Thin basement membrane nephropathy (TBMN) is often attributable to mutations in the COL4A3 or COL4A4 genes that encode the alpha3 and alpha4 chains of type IV collagen, respectively, a major structural protein in the glomerular basement membrane. The aim of this study was to explore a new disease-related genetic mutation associated with the clinical phenotype observed in a Chinese Han family with autosomal dominant TBMN. We conducted a clinical and genetic study comprising seven members of this TBMN family. Mutation screening for COL4A3 and COL4A4 was carried out by direct sequencing. The RNA sequences associated with both proteins were also analyzed with reverse transcription PCR and TA cloning. The result showed that every affected patient had a novel heterozygous splicing mutation in COL4A4 (c.1459 + 1G > A), which led to the elimination of the entire exon 21 from the COL4A4 cDNA and resulted in the direct splicing of exons 20 and 22. This in turn caused a frameshift mutation after exon 20 in the open reading frame of COL4A4. In conclusion, we describe a novel splicing mutation in COL4A4 that results in TBMN. This analysis increases our understanding of TBMN phenotype genotype correlations, which should facilitate more accurate diagnosis and prenatal diagnosis of TBMN. PMID- 26833246 TI - New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk. AB - To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 * 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk. PMID- 26833264 TI - Novel functional microRNAs from virus-free and infected Vitis vinifera plants under water stress. AB - MicroRNAs (miRNAs) are small non-coding RNAs that regulate the post transcriptional control of several pathway intermediates, thus playing pivotal roles in plant growth, development and response to biotic and abiotic stresses. In recent years, the grapevine genome release, small(s)-RNAseq and degradome RNAseq together has allowed the discovery and characterisation of many miRNA species, thus rendering the discovery of additional miRNAs difficult and uncertain. Taking advantage of the miRNA responsiveness to stresses and the availability of virus-free Vitis vinifera plants and those infected only by a latent virus, we have analysed grapevines subjected to drought in greenhouse conditions. The sRNA-seq and other sequence-specific molecular analyses have allowed us to characterise conserved miRNA expression profiles in association with specific eco-physiological parameters. In addition, we here report 12 novel grapevine-specific miRNA candidates and describe their expression profile. We show that latent viral infection can influence the miRNA profiles of V. vinifera in response to drought. Moreover, study of eco-physiological parameters showed that photosynthetic rate, stomatal conductance and hydraulic resistance to water transport were significantly influenced by drought and viral infection. Although no unequivocal cause-effect explanation could be attributed to each miRNA target, their contribution to the drought response is discussed. PMID- 26833266 TI - The effect of exercise on sleep quality and psychological, physiological, and biological correlates in patients with schizophrenia: A pilot study. PMID- 26833265 TI - Shared and distinct gray matter abnormalities in schizophrenia, schizophrenia relatives and bipolar disorder in association with cognitive impairment. AB - Cognitive impairments have been linked to structural and functional alterations in frontal and subcortical brain regions, ultimately leading to fronto-thalamic connectivity disturbances. We hypothesized that such neuronal disruptions in frontal and subcortical structures may account for neuropsychological deficits in schizophrenia (SZ), schizophrenia relatives and bipolar disorder (BD). We acquired T1-weighted anatomical MRI sequences in 209 participants: 57 SZ patients, 47 first-degree relatives of SZ patients, 48 BD I patients and 57 healthy controls. We computed group comparisons of gray matter (GM) volume in frontal and basal ganglia regions-of-interest, followed by correlation analysis between psychomotor speed, executive functioning and learning and GM volumes in candidate regions. Several frontal GM volume reductions as well as GM increases in the thalamus and the putamen were exhibited in SZ patients as compared to controls. The same finding was observed - less pronounced - when comparing SZ relatives and controls. BD patients presented GM volume increases in the basal ganglia in comparison to controls. In SZ patients, increases in bilateral thalamus GM volume and decreases in left middle and superior frontal gyrus volume were significantly associated with worse cognitive performance. In summary, our results indicate distinct imbalances across frontal-subcortical circuits in BD, SZ relatives and SZ. The functional relevance of the findings were mainly limited to the SZ patients group: in this group, abnormalities were directly associated with cognitive performance. This result is in line with the finding that the volume alterations were strongest in SZ patients and followed by BD patients and SZ relatives. PMID- 26833267 TI - Role of learning potential in cognitive remediation: Construct and predictive validity. AB - BACKGROUND: The construct, convergent, discriminant, and predictive validity of Learning Potential (LP) was evaluated in a trial of cognitive remediation for adults with schizophrenia-spectrum disorders. LP utilizes a dynamic assessment approach to prospectively estimate an individual's learning capacity if provided the opportunity for specific related learning. METHODS: LP was assessed in 75 participants at study entry, of whom 41 completed an eight-week cognitive remediation (CR) intervention, and 22 received treatment-as-usual (TAU). LP was assessed in a "test-train-test" verbal learning paradigm. Incremental predictive validity was assessed as the degree to which LP predicted memory skill acquisition above and beyond prediction by static verbal learning ability. RESULTS: Examination of construct validity confirmed that LP scores reflected use of trained semantic clustering strategy. LP scores correlated with executive functioning and education history, but not other demographics or symptom severity. Following the eight-week active phase, TAU evidenced little substantial change in skill acquisition outcomes, which related to static baseline verbal learning ability but not LP. For the CR group, LP significantly predicted skill acquisition in domains of verbal and visuospatial memory, but not auditory working memory. Furthermore, LP predicted skill acquisition incrementally beyond relevant background characteristics, symptoms, and neurocognitive abilities. CONCLUSIONS: Results suggest that LP assessment can significantly improve prediction of specific skill acquisition with cognitive training, particularly for the domain assessed, and thereby may prove useful in individualization of treatment. PMID- 26833268 TI - Redefining the induction of periodontal tissue regeneration in primates by the osteogenic proteins of the transforming growth factor-beta supergene family. AB - The molecular bases of periodontal tissue induction and regeneration are the osteogenic proteins of the transforming growth factor-beta (TGF-beta) supergene family. These morphogens act as soluble mediators for the induction of tissues morphogenesis sculpting the multicellular mineralized structures of the periodontal tissues with functionally oriented ligament fibers into newly formed cementum. Human TGF-beta3 (hTGF-beta3 ) in growth factor-reduced Matrigel(r) matrix induces cementogenesis when implanted in class II mandibular furcation defects surgically prepared in the non-human primate Chacma baboon, Papio ursinus. The newly formed periodontal ligament space is characterized by running fibers tightly attached to the cementoid surface penetrating as mineralized constructs within the newly formed cementum assembling and initiating within the mineralized dentine. Angiogenesis heralds the newly formed periodontal ligament space, and newly sprouting capillaries are lined by cellular elements with condensed chromatin interpreted as angioblasts responsible for the rapid and sustained induction of angiogenesis. The inductive activity of hTGF-beta3 in Matrigel(r) matrix is enhanced by the addition of autogenous morcellated fragments of the rectus abdominis muscle potentially providing myoblastic, pericytic/perivascular stem cells for continuous tissue induction and morphogenesis. The striated rectus abdominis muscle is endowed with stem cell niches in para/perivascular location, which can be dominant, thus imposing stem cell features or stemness to the surrounding cells. This capacity to impose stemness is morphologically shown by greater alveolar bone induction and cementogenesis when hTGF-beta3 in Matrigel(r) matrix is combined with morcellated fragments of autogenous rectus abdominis muscle. The induction of periodontal tissue morphogenesis develops as a mosaic structure in which the osteogenic proteins of the TGF-beta supergene family singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis. In primates, the presence of several homologous yet molecularly different isoforms with osteogenic activity highlights the biological significance of this apparent redundancy and indicates multiple interactions during embryonic development and bone regeneration in postnatal life. Molecular redundancy with associated different biological functionalities in primate tissues may simply represent the fine-tuning of speciation-related molecular evolution in anthropoid apes at the early Pliocene boundary, which resulted in finer tuning of the bone induction cascade. PMID- 26833269 TI - Application of Deuteporfin in the Metastatic Lymph Node Mapping of Pancreatic Cancer: An in vivo Study. AB - For most cancer patients, the presence of metastatic lymph nodes usually indicates regional recurrence and poor prognosis. Therefore, lymph node mapping is a requisite for disease staging, prognosis prediction and decision making in the treatment of cancer. Deuteporfin, a second-generation photosensitizer, has a maximum excitation wavelength that can reach the near infrared (NIR) region (650 700 nm). We aimed to take advantage of these aspects of deuteporfin and use it as a fluorescent probe for metastatic lymph node mapping in vivo using NIR fluorescent imaging. In our study, we further investigated whether a photosensitizer could be used as a tracer for metastatic lymph node mapping of pancreatic cancer based on previous reports. Compared to normal tissues, tumor tissues including primary tumors and metastatic lymph nodes had a higher uptake ability of deuteporfin (P < 0.05). Our research confirmed this targeting property of deuteporfin using in vivo fluorescent imaging. Consistent with observations from in vivo imaging experiments, frozen sections of metastatic lymph nodes intuitively displayed significantly higher and wider distributions of deuteporfin than normal sections. PMID- 26833263 TI - Viral hepatitis vaccination during pregnancy. AB - Viral hepatitis is a serious global public health problem. It is also a common cause of jaundice and gestational complications in pregnant women. Moreover, infected mothers can transmit the virus to their fetus or neonate, which may increase disease burden and decrease quality of life. To date, commercial vaccines have been developed for hepatitis A, B, and E and are available to the general population. The Advisory Committee on Immunization Practices currently accepts emergency vaccination against hepatitis A and B during pregnancy due to benefits that overweight the potential risks. While there are limited data from trials with limited numbers of samples that suggest the efficacy or safety of hepatitis B and E vaccines in pregnant women, additional data are necessary to provide evidence of vaccination during pregnancy. PMID- 26833271 TI - Editor's note: The changing face of European Neuropsychopharmacology. PMID- 26833270 TI - Assessing the impact of a nurse-delivered home dried blood spot service on uptake of testing for household contacts of hepatitis B-infected pregnant women across two London trusts. AB - Despite national guidance recommending testing and vaccination of household contacts of hepatitis B-infected pregnant women, provision and uptake of this is sub-optimal. The aim of this study was to evaluate the use of in-home dried blood spot (DBS) testing to increase testing and vaccination of household contacts of hepatitis B-infected pregnant women as an alternative approach to conventional primary-care follow-up. The study was conducted across two London maternity trusts (North Middlesex and Newham). All hepatitis B surface antigen-positive pregnant women identified through these trusts were eligible for inclusion. The intervention of in-home DBS testing for household contacts was introduced at North Middlesex Trust from November 2010 to December 2011. Data on testing and vaccination uptake from GP records across the two trusts were compared between baseline (2009) and intervention (2010-2011) periods. In-home DBS service increased testing uptake for all ages (P < 0.001) with the biggest impact seen in partners, where testing increased from 30.3% during the baseline period to 96.6% during the intervention period in North Middlesex Trust. Although impact on vaccine uptake was less marked, improvements were observed for adults. The provision of nurse-led home-based DBS may be useful in areas of high prevalence. PMID- 26833272 TI - Evaluation of learning disabilities in segmental neurofibromatosis. PMID- 26833273 TI - Epigenomics in marine fishes. AB - Epigenetic mechanisms are an underappreciated and often ignored component of an organism's response to environmental change and may underlie many types of phenotypic plasticity. Recent technological advances in methods for detecting epigenetic marks at a whole-genome scale have launched new opportunities for studying epigenomics in ecologically relevant non-model systems. The study of ecological epigenomics holds great promise to better understand the linkages between genotype, phenotype, and the environment and to explore mechanisms of phenotypic plasticity. The many attributes of marine fish species, including their high diversity, variable life histories, high fecundity, impressive plasticity, and economic value provide unique opportunities for studying epigenetic mechanisms in an environmental context. To provide a primer on epigenomic research for fish biologists, we start by describing fundamental aspects of epigenetics, focusing on the most widely studied and most well understood of the epigenetic marks: DNA methylation. We then describe the techniques that have been used to investigate DNA methylation in marine fishes to date and highlight some new techniques that hold great promise for future studies. Epigenomic research in marine fishes is in its early stages, so we first briefly discuss what has been learned about the establishment, maintenance, and function of DNA methylation in fishes from studies in zebrafish and then summarize the studies demonstrating the pervasive effects of the environment on the epigenomes of marine fishes. We conclude by highlighting the potential for ongoing research on the epigenomics of marine fishes to reveal critical aspects of the interaction between organisms and their environments. PMID- 26833274 TI - Involvement of the GABAA Receptor in Age-Dependent Differences in Binge-Like Ethanol Intake. AB - BACKGROUND: Binge alcohol (ethanol [EtOH]) drinking is common during adolescence, a time characterized by many behavioral and neurobiological changes. Among them, the GABAA receptor system undergoes substantial modifications, including changes in the density, distribution, and subunit composition of the receptor. Based on its demonstrated role in EtOH consumption, this study aimed to investigate the effects of 2 different GABAA receptor agonists on binge-like EtOH intake in adolescent and adult mice using the Drinking-in-the-Dark model. METHODS: Three hours into their dark cycle, adolescent (postnatal day 28 [P28]) and adult (P63) male C57BL/6J mice were given daily access to 20% EtOH for 2 hours during 8 consecutive days. Immediately before the access on day 8, mice (P35 and P70) were systemically injected with 1 of 2 different GABAergic drugs. The effects of muscimol, a full GABAA agonist, were assessed in a first experiment. The second experiment tested for the more specific involvement of delta-containing extrasynaptic GABAA receptors through the administration of THIP (4,5,6,7 tetrahydroisoxazolo(5,4-c)pyridin-3-ol). RESULTS: Adolescent mice consumed more EtOH than their adult counterparts. Following the administration of GABAA agonists, levels of EtOH intake were reduced at both ages. However, age-dependent differences were revealed following the administration of THIP, with adolescents exhibiting greater sensitivity to its suppressant effects, especially during the first 30 minutes of binge EtOH access. CONCLUSIONS: This study adds to the existing literature demonstrating the crucial role of the GABAA receptor in alcohol consumption. In addition, it suggests that age differences in the GABAA receptor modulation of binge alcohol drinking might be more dependent on extrasynaptic GABAA receptors. PMID- 26833275 TI - Comparative efficacy of G6G and Ovsynch protocols on synchronization and pregnancy rate in Nili-Ravi buffalo. AB - The aim of this work was to evaluate the efficacy of G6G and Ovsynch protocols on synchronization and pregnancy rate in Nili-Ravi buffalo. For this, a total of fifty buffalo were assigned into two treatment groups: (1) G6G (n=25) and (2) Ovsynch (n=25). The blood samples were collected from all the treated buffalo on day (D) 7 (PGF2alpha injection of Ovsynch) to measure the progesterone (P4). All the buffalo were fixed time inseminated (FTAI) following last GnRH of Ovsynch. Ultrasonography was performed for follicular, corpus luteum (CL) dynamics and pregnancy diagnosis. The results revealed that synchronization rate and response to final PGF2alpha were significantly (P<0.05) higher in G6G compared to Ovsynch. The ovulation to first GnRH of Ovsynch was higher (P<0.05) in G6G (84%) than Ovsynch (56%). The mean dominant follicle size following last GnRH of Ovsynch showed significantly larger diameter in G6G (11.7+/-0.2mm) compared to Ovsynch (10.9+/-0.2mm). Moreover, the higher (P<0.05) P4 concentration was observed in G6G than Ovsynch. The presence of double CL on D 7 was higher (P<0.05) in G6G (64%) than Ovsynch (24%) group. The pregnancy rate (P=0.08) tended to be greater in G6G compared to Ovsynch. In conclusion, G6G treatment showed better ovulatory and luteolytic response to first GnRH and PGF2alpha compared to Ovsynch treatment. Moreover, the addition of GnRH and PGF2alpha prior to Ovsynch is helpful to improve synchronization application of Ovsynch protocol in Nili-Ravi buffalo. PMID- 26833276 TI - Motives and activities for continuing professional development: An exploration of their relationships by integrating literature and interview data. AB - BACKGROUND: To effectively enhance professional development, it is important to understand the motivational factors behind nurses' engagement in particular types of learning activities. Nurses have various motives for professional development and utilise different learning activities. Not much is known about how these relate. OBJECTIVES: The aim of this study was to explore the relationship between nurses' motives and activities for continuing professional development, by examining in which types of learning activities nurses engage, with which motives, and whether certain motives are associated with certain learning activities. DESIGN: A qualitative study using semi-structured interviews. SETTINGS AND PARTICIPANTS: Twenty-one nurses in academic and general Dutch hospitals participated. METHODS: Interview data on nurses' learning biographies were analysed using a literature-based framework on motives and learning activities for continuing professional development. As recent classifications of nurses' motives for professional development were absent, the literature was reviewed for motives, using three databases. The interview transcripts were analysed for motives, learning activities and their relationships. RESULTS: Nine motives and four categories of learning activities for continuing professional development were delineated. Increasing competence was the primary motive that stimulated nurses to engage in self-directed learning during work, and in formal learning activities. To comply with requirements, they engaged in mandatory courses. To deepen knowledge, they registered for conferences. To develop their careers, they enrolled in postgraduate education. Five other motives were not mentioned as frequently. CONCLUSIONS: Specific motives were found to be related to engagement in particular learning activities. Nurses could use these findings to increase their awareness of why and how they develop professionally, and managers and human resource development professionals could develop approaches that would better suit nurses' needs. PMID- 26833278 TI - DNA damage and antioxidants in treatment naive children with obsessive-compulsive disorder. AB - The current study aimed to investigate whether serum antioxidant levels and DNA damage differ between the children and adolescents with Obsessive Compulsive Disorder (OCD) and healthy controls. The study included 31 children (Male/Female, 22/9; age range 7-17 years), with treatment naive OCD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) and 28 age- and gender-matched healthy control subjects. Children's Yale Brown Obsession Compulsion Scale (CY-BOC) was applied to the children. Glutathione peroxidase (GPx), superoxide dismutase (SOD), coenzyme Q (CoQ), and 8-Hydroxy-2 Deoxyguanosine (8-OHdG) were all measured by the enzyme-linked immunosorbent assay method. GPx, CoQ and 8-OHdG levels were found to be significantly higher in the OCD group, compared to the control group (p=0.010, p=0.034, p=0.010, respectively); however, no significant difference was found in the SOD levels between two groups (p=0.10). There were no correlations between the CY-BOC scores, depression scores, duration of the disease and biochemical parameters (p>0.05, for all). Children with OCD were found to have higher antioxidant levels and oxidative DNA damage. The findings of this study support the role of oxidative stress in the pathogenesis of OCD. In this regard, any possible effect of adding antioxidants to conventional treatment can be investigated. PMID- 26833277 TI - Selection preserves Ubiquitin Specific Protease 4 alternative exon skipping in therian mammals. AB - Ubiquitin specific protease 4 (USP4) is a highly networked deubiquitinating enzyme with reported roles in cancer, innate immunity and RNA splicing. In mammals it has two dominant isoforms arising from inclusion or skipping of exon 7 (E7). We evaluated two plausible mechanisms for the generation of these isoforms: (A) E7 skipping due to a long upstream intron and (B) E7 skipping due to inefficient 5' splice sites (5'SS) and/or branchpoint sites (BPS). We then assessed whether E7 alternative splicing is maintained by selective pressure or arose from genetic drift. Both transcript variants were generated from a USP4-E7 minigene construct with short flanking introns, an observation consistent with the second mechanism whereby differential splice signal strengths are the basis of E7 skipping. Optimization of the downstream 5'SS eliminated E7 skipping. Experimental validation of the correlation between 5'SS identity and exon skipping in vertebrates pinpointed the +6 site as the key splicing determinant. Therian mammals invariably display a 5'SS configuration favouring alternative splicing and the resulting isoforms have distinct subcellular localizations. We conclude that alternative splicing of mammalian USP4 is under selective maintenance and that long and short USP4 isoforms may target substrates in various cellular compartments. PMID- 26833279 TI - Theory of mind correlates with clinical insight but not cognitive insight in patients with schizophrenia. AB - Research on the relationship between insight and social cognition, in particular Theory of Mind (ToM), in schizophrenia has yielded mixed findings to date. Very few studies, however, have assessed both clinical insight and cognitive insight when examining their relationships with ToM in schizophrenia. The current study thus investigated the relationship between clinical insight, cognitive insight, and ToM in a sample of 56 patients with schizophrenia and 30 healthy controls. Twenty-seven patients were classified as low in clinical insight according to their scores on the 'insight' item (G12) of the Positive and Negative Syndrome Scale (PANSS). Moreover, cognitive insight and ToM were assessed with the Beck Cognitive Insight Scale (BCIS) and the Yoni task, respectively. The results indicated that patients with poor clinical insight performed worse on tasks of second-order cognitive and affective ToM, while the ToM performance of patients with high clinical insight was equivalent to that of healthy controls. Furthermore, while clinical insight was correlated with ToM and clinical symptoms, cognitive insight did not correlate with clinical insight, ToM, or clinical symptoms. Clinical insight thus appears to be an important factor related to ToM in schizophrenia. PMID- 26833280 TI - Associations between depression risk, bullying and current smoking among Chinese adolescents: Modulated by gender. AB - This school-based study aimed to investigate the prevalence of being at risk for depression, bullying behavior, and current smoking among Chinese adolescents in order to explore gender differences in the vulnerability of adolescents with these behaviors to develop a smoking habit. A total of 35,893 high school students sampled from high schools in eighteen cities in China participated in the study from 2011 to 2012. Overall, the prevalence of current smoking was estimated at 6.4%. In total, 1.7% (618) of the participants admitted to bullying others, 5.8% (2071) reported being bullied, 3.5% (1269) were involved in both bullying others and being bullied, and 5.6% (2017) were at high risk for depression. Logistic regression analysis indicated that among girls, with high depression risk, bullying others, being bullied, and both bullying others and being bullied were independently and positively associated with current smoking habits, while the final results among boys showed that bullying others and both bullying others and being bullied were independently associated with an increased risk of current smoking. School-based prevention programs are highly recommended, and we should focus on high-risk students, particularly girls with high risk of depression or involved in school bullying and boys who are involved in school bullying. PMID- 26833281 TI - Psychopathy in women: Prediction of criminality and violence in UK and USA psychiatric patients resident in the community. AB - Psychopathy is an important clinical construct often used in the assessment and management of psychiatric patients and offenders. This, in part, is due to the strong association between psychopathy, crime, and particularly violent crime. However, there are few studies of these associations in women. These relationships were examined using information from two large databases. The Partnerships in Care database contains data from a sample of forensic psychiatric patients (154 women and 777 men) in the UK that were discharged from secure psychiatric units. Follow-up was via official conviction data within the next 2 years. The MacArthur study examined violence and aggression in a sample of civil psychiatric patients (367 women and 496 men) in the USA following discharge from an acute psychiatric hospital. Follow-up was via a mixture of self-report, informant report and official records. Psychopathy in both samples was measured via the PCL:SV prior to discharge. Psychopathy was a good predictor of target events for the women in both samples and for all time intervals used. No significant gender differences in the PCL:SV's predictive efficacy were found. The results provide a strong evidence-base for the use of psychopathy in women when considering future community behaviour and reoffending. PMID- 26833282 TI - Fluidizing and Solidifying Effects of Perfluorooctylated Fatty Alcohols on Pulmonary Surfactant Monolayers. AB - Pulmonary surfactant (PS) preparations based mainly on bovine or porcine extracts are commonly administered to patients with neonatal respiratory distress syndrome (NRDS) for therapy. The preparations are sufficiently effective to treat NRDS; however, they are associated with a risk of infection and involve costly purification procedures to achieve batch-to-batch reproducibility. Therefore, we investigated the mechanism and interfacial behavior of synthetic PS preparations containing a mimicking peptide (KLLKLLLKLWLKLLKLLL, Hel 13-5). In particular, a hybrid PS formulation with fluorinated amphiphiles is reported from the perspective of surface chemistry. Fluorinated amphiphiles are characterized by exceptional chemical and biological inertness, high oxygen-dissolving capacity, low surface tension, excellent spreading ability, and high fluidity. These properties are superior to those for the corresponding hydrocarbon analogs. Indeed, a small amount of fluorinated long-chain alcohols enhances the effectiveness of the model PS preparation for in vitro pulmonary functions. Moreover, the mode of the improved efficacy differs depending on the hydrophobic chain length in the alcohols. For alcohols with a short fluorocarbon (FC) chain, the monolayer phase of the model PS preparation remains disordered (fluidization). However, the addition of alcohols containing a long FC chain reduces the disordered/ordered phase transition pressure and the growth of ordered domains of the monolayer (condensation). Furthermore, repeated compression-expansion isotherms of the monolayers, which can simulate respiration in the lung, suggest irreversible elimination of the short-FC alcohol into the subphase and enhancement of the squeeze-out phenomenon of certain PS components by solid-like monolayer formation induced by the long-FC alcohol. We demonstrated that fluorinated amphiphiles may be used as additives for synthetic or commercial PS preparations for RDS treatment. PMID- 26833283 TI - Effects of Temperature and Humidity History on Brittleness of alpha-Sulfonated Fatty Acid Methyl Ester Salt Crystals. AB - alpha-Sulfonated fatty acid methyl ester salts (MES), which were made from vegetable sources, are attractive candidates for eco-friendly washing detergents because they have various special features like excellent detergency, favorable biodegradability, and high stability against enzymes. To overcome some disadvantages of powder-type detergents like caking, sorting, and dusting, we studied how temperature and humidity history, as a model for long-term storage conditions, can affect crystalline structures and reduce the brittleness of MES powder. We characterized the crystalline structure of MES grains using small angle X-ray scattering, wide-angle X-ray scattering, differential scanning calorimetry, and Fourier transform infrared spectroscopy measurements and determined the yield values, which measure the brittleness of MES grains, in shear stress using dynamic viscoelasticity measurements. This study confirmed that MES crystals form three pseudo-polymorphs via thermal or humidity conditioning: metastable crystals (alphasubcell), anhydrous crystals (beta subcell), and dihydrate crystals (beta' subcell). Further, we found that the yield value increases upon phase transition from the beta subcell to the beta' subcell and from the beta' subcell to the alphasubcell. Therefore, controlling the thermal and humidity conditioning of MES grains is an effective way to decrease the brittleness of MES powders and can be used to overcome the above mentioned disadvantages of powder-type detergents in the absence of co surfactants. PMID- 26833284 TI - Preparation of Diacylglycerol-enriched Rice Bran Oil by Lipase-catalyzed Deacidification in Packed-bed Reactors by Continuous Dehydration. AB - Diacylglycerol-enriched rice bran oil (RBO-DAG) was produced by deacidification of high-acid rice bran oil (RBO) with glycerol (Gly) using Lipozyme RM IM by continuous dehydration by combination of two enzyme columns (column 1 and 3, used for deacidification) with one molecular sieves column (column 2, used for dehydration). The conditions for three columns were respectively optimized. Response surface methodology (RSM) was used to optimize the conditions of column 1. The content of DAG and conversion of free fatty acid (FFA) were used as indicators and the effects of the enzyme load (8-12 g), flow rate (0.3-0.6 mL/min), substrate molar ratio (4-6) and reaction temperature (55-75 degrees C) were investigated. The content of DAG and conversion of FFA were significantly correlated to the flow rate and substrate molar ratio. Most desirable conditions of the reaction with respect to the maximal DAG content and FFA conversion was attained under the residence time of 40 min, substrate molar ratio of 5.52 (Gly: RBO) and temperature of 66 degrees C. The conditions for column 2 were investigated by varying molecular sieves load and flow rate, and the maximal dehydration rate of 85.22% was obtained under the optimal conditions. For column 3, the optimum conditions were obtained as: flow rate, 0.2mL/min; temperature, 65 degrees C, and the content of DAG and FFA were 38.99% and 3.04%, respectively under these conditions. The catalytic activity of the lipase was stable in twelve continuous operations with 83.22% of its original ability, demonstrating its potential in the continuous packed-bed reactors (PBRs) system. These results showed that packed-bed reactors combined with continuous deacidification and dehydration in one system had great value in industrial production for high-acid RBO with the improved conversion rate. PMID- 26833285 TI - Potential Biosignificant Interest and Surface Activity of Efficient Heterocyclic Derivatives. AB - Some functionalized pyridine and fused system derivatives were synthesized using enaminonitrile derivative 5 as a starting material for the reaction, with various reagents under different conditions. Propoxylation of these compounds using different moles of propylene oxide (3, 5 and 7 moles) leads to a novel group of surface active agents. The antimicrobial and surface activities of the synthesized compounds were investigated. Most of the evaluated compounds proved to be active as antibacterial and antifungal agents and showed good surface activity, which makes them suitable for diverse applications such as the manufacturing of emulsifiers, cosmetics, drugs, pesticides, etc. Additionally, biodegradation testing exhibits significant breakdown within six to seven days, and hence, lowers the toxicity to human beings and becomes environmentally friendly. PMID- 26833286 TI - Fifteen new earthworm mitogenomes shed new light on phylogeny within the Pheretima complex. AB - The Pheretima complex within the Megascolecidae family is a major earthworm group. Recently, the systematic status of the Pheretima complex based on morphology was challenged by molecular studies. In this study, we carry out the first comparative mitogenomic study in oligochaetes. The mitogenomes of 15 earthworm species were sequenced and compared with other 9 available earthworm mitogenomes, with the main aim to explore their phylogenetic relationships and test different analytical approaches on phylogeny reconstruction. The general earthworm mitogenomic features revealed to be conservative: all genes encoded on the same strand, all the protein coding loci shared the same initiation codon (ATG), and tRNA genes showed conserved structures. The Drawida japonica mitogenome displayed the highest A + T content, reversed AT/GC-skews and the highest genetic diversity. Genetic distances among protein coding genes displayed their maximum and minimum interspecific values in the ATP8 and CO1 genes, respectively. The 22 tRNAs showed variable substitution patterns between the considered earthworm mitogenomes. The inclusion of rRNAs positively increased phylogenetic support. Furthermore, we tested different trimming tools for alignment improvement. Our analyses rejected reciprocal monophyly among Amynthas and Metaphire and indicated that the two genera should be systematically classified into one. PMID- 26833288 TI - Childhood, Wellness, and Nonlocal Consciousness. PMID- 26833287 TI - Fibrocartilaginous embolism: a comprehensive review of an under-studied cause of spinal cord infarction and proposed diagnostic criteria. AB - BACKGROUND: Most spinal cord infarctions are due to aortic pathologies and aortic surgeries. Fibrocartilaginous Embolism (FCE) has been reported to represent 5.5% of spinal cord infarctions. Some believe that FCE is more common than presumed and is rather under-diagnosed due to vagueness surrounding its clinical presentation. METHOD: A literature search was conducted for case reports of FCE published before August 2014. PubMed, the Cochrane Central Register and Google Scholar were searched for different combinations of the key words "fibrocartilaginous, "nucleus pulposus", "embolism", "spinal cord", "inter vertebral disc", "infarction", "stroke", "paraplegia", "quadriplegia", "myelopathy". RESULT: Fifty-five case articles were reviewed, ten of which were translated from foreign languages. A total of 67 cases of FCE were found, 41 tissue-confirmed and 26 clinically suspected. A comprehensive summary of the clinical anatomy, patho-physiologic mechanisms, epidemiology, diagnosis and treatment of FCE is described, along with the conflicting opinions on its incidence and relevance after reviewing all of the related literature. The 41 tissue proven cases are summarized and a schematic approach to the clinical diagnosis of FCE, deducted from their clinical findings, is presented. CONCLUSION: FCE of the spinal cord, often mis-diagnosed as transverse myelitis, may be more common than presumed. Future research into FCE, including the development of a chondrolytic therapy that can be given empirically upon its clinical suspicion to acutely reverse its symptoms, may be of value. PMID- 26833289 TI - Potential applications of fish oils rich in omega-3 polyunsaturated fatty acids in the management of gastrointestinal cancer. AB - BACKGROUND & AIMS: Despite advances in chemotherapeutic agents and surgical approaches for its management, gastrointestinal cancer still accounts for 27% of new cancer cases and 35% of cancer related mortality worldwide. Omega-3 polyunsaturated fatty acids (PUFAs) specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory and anticancer activities and are used as immuno-nutrients. METHODS: A literature search was conducted to identify primary research reporting on applications of the omega-3 PUFAs in gastrointestinal cancer. RESULTS: Reported laboratory studies indicate a clear role for omega-3 PUFAs in preventing cancer development at various stages including cancer cell proliferation, survival, angiogenesis, inflammation and metastasis. In clinical settings, omega-3 PUFAs have been reported to improve the immune response, maintain lean body mass, improve quality of life and improve overall survival in patients with colorectal and pancreatic cancer. In contrast to other GI cancers, there is a strong connection between inflammation and oesophageal cancer. CONCLUSIONS: Little work has been done exploring the role for omega-3 PUFAs in oesophageal cancer prevention and management. The authors are conducting a clinical trial investigating the use of parenteral omega-3 PUFAs supplementary to the standard of care (epirubicin, oxaliplatin and capecitabine palliative chemotherapy) in patients with advanced oesophagogastric cancer as a promising new therapeutic approach. PMID- 26833290 TI - Advancing nutritional therapy: A novel polymeric formulation attenuates intestinal inflammation in a murine colitis model and suppresses pro-inflammatory cytokine production in ex-vivo cultured inflamed colonic biopsies. AB - BACKGROUND & AIMS: Nutritional therapy is a viable therapeutic option for the treatment of Crohn disease (CD). Therefore improving nutritional therapy would greatly benefit CD patients. The aim of this study was to define the anti inflammatory properties of a novel nutritional polymeric formula (PF) in comparison to a currently available standard PF. METHODS: Dextran sodium sulfate (DSS) was utilized to induce colitis in C57BL/6 mice with mice randomized to receive either standard PF or novel PF in addition to control groups. Changes in body weight were recorded and colonic damage was assessed histologically and biochemically. Additional experiments were also included where the cytokine response of colonic biopsies from pediatric CD patients was measured following exposure to standard PF or novel PF. RESULTS: DSS induced significant body weight loss, morphological changes in the colon, increased myeloperoxidase (MPO) activity and up-regulated colonic mRNA expression of tumor necrosis factor (TNF) alpha, interleukin (IL)-6, IL-12 and monocyte chemoattractant protein (MCP)-1, as well as associated histological changes. Other than histological damage, these inflammatory changes were reversed by both novel and standard PF. However, the novel PF, but not standard PF, completely suppressed TNF-alpha, IL-6 and IL-8 levels from cultured biopsies. CONCLUSIONS: Newly developed nutritional formula reproducibly ameliorated DSS-induced colitis in a murine model, although this response was not measurably different to standard PF. However, the novel PF was significantly superior in suppressing inflammatory cytokine release from cultured colonic biopsies. Collectively, these findings support a possible role for novel PF in advancing nutritional therapy for CD patients. PMID- 26833291 TI - Analysis of Layperson Tourniquet Application Using a Novel Color-Coded Device. AB - OBJECTIVE: To determine whether a color-coded tourniquet designed for public use increases successful tourniquet application by laypeople. METHODS: This was a randomized study conducted on April 25, 2015. The study occurred during the Maryland Day activity at the University of Maryland in College Park, Maryland. Investigators recruited participants with posters displayed at major crosswalks around a central testing area. A total of 157 volunteers aged 18 years or older and without prior military service or medical training were enrolled. A participant stood in front of a waist-down mannequin with an isolated leg injury while an investigator read aloud a mass causality scenario. The investigator then asked the participant to apply a tourniquet to the mannequin's leg. All participants received a 4-step illustrated just-in-time (JiT) instruction card designed to facilitate layperson tourniquet application. Test participants received a color-coded tourniquet designed for layperson use with instructions printed on the device. Control participants received a black Combat Application Tourniquet (C-A-T; Composite Resources, Rock Hill, SC). Participants were randomized in a 1:1 ratio in blocks of 50. The primary outcome was the proportion of successful tourniquet applications by those who received color-coded tourniquets compared to those who received black tourniquets. Secondary outcomes included validation of previous data analyzing layperson success with tourniquet application, time for successful placement, reasons for failed applications, and participant self-willingness and comfort using tourniquets. We also analyzed demographic data on the study population and inter-rater reliability regarding the assessment of successful tourniquet application. RESULTS: Participants supplied with color-coded tourniquets successfully placed the device 51.38% of the time, compared to 44.71% of the time for controls using a black tourniquet (risk ratio: 1.15; 95% confidence interval: 0.83-1.59; P=0.404). Participants' self-reported willingness to use a tourniquet rose from 40.8% before the study to 80.3% after the study (P<0.05). CONCLUSIONS: The color-coded device did not significantly increase laypeople's proportion of successful tourniquet applications when compared with a standard black device. However, this study reproduced pilot study data showing that laypeople can successfully apply tourniquets about half the time if provided JiT instructions. Age, sex, race, income, and highest level of education were not found to impact one's ability to properly apply a tourniquet. Laypeople's willingness to apply tourniquets doubled to 80% after brief exposure to the device. These results affirm the feasibility of engaging laypeople as immediate lifesavers of trauma victims and justify further efforts to boost rates of proper application. PMID- 26833292 TI - Towards a sustainable dispensing separation model. PMID- 26833293 TI - A water-soluble and fast-response mitochondria-targeted fluorescent probe for colorimetric and ratiometric sensing of endogenously generated SO2 derivatives in living cells. AB - A novel water-soluble mitochondria-targeted ratiometric fluorescent probe (Cl-2) is presented. Cl-2 can respond selectively to SO2 derivatives within 1 min. Notably, Cl-2 can be used to monitor successfully the concentration change of endogenously generated SO2 derivatives in living cells. PMID- 26833294 TI - An irish case of limb-girdle muscular dystrophy 2I with structural eye involvement. PMID- 26833297 TI - Prevalence of Fabry disease among Turkish dialysis patients: Data from hemodialysis centers in Bursa province. AB - BACKGROUND: Detection of potential Fabry disease patients before appearance of life-threatening findings is of great importance, particularly in high-risk populations. This study was designed to determine prevalence of Fabry disease among Turkish patients undergoing peritoneal dialysis and hemodialysis for chronic renal failure (CRF). METHODS: A total of 1,527 patients (mean (SD) age: 60.2 (14.2) years, 55.5% were males) on hemodialysis (n = 1,435) or peritoneal dialysis (n = 92) for CRF were included in this multicenter study conducted at 17 dialysis centers across Bursa province, Turkey. Prevalence of the disease was determined using combined enzymatic and genetic strategy with measuring the activity of alpha-galactosidase A (alpha-Gal A) and Sanger sequence analysis based genotyping in alpha-galactosidase A gene (GLA) in dried blood samples (DBS). RESULTS: Overall alpha-Gal A activity was determined to be below the reference value in 130 (8.5%) of 1,527 patients. GLA genotyping confirmed the diagnosis of Fabry disease in 5 (0.3%) patients with low alpha-Gal A activity. All Fabry-positive patients were males corresponding to a 0.6% prevalence of disease in this gender. CONCLUSION: In conclusion, our findings, which were based on the use of DBS for both enzymatic activity and genotyping analyses, revealed the diagnosis of Fabry disease in 5 males corresponding to overall 0.3% prevalence of disease in the cohort and 0.6% prevalence among males. Our results support the likelihood of unrecognized Fabry disease in a nonnegligible number of patients on dialysis and thus emphasize the value of screening studies in terms of detection of new cases and improved prognosis of the disease via early diagnosis and treatment. PMID- 26833298 TI - Bone histomorphometry and indicators of bone and mineral metabolism in wait listed dialysis patients. AB - AIMS: The aim of this study was to evaluate the associations between bone histomorphometry and bone volume measured by dual-energy X-ray absorptiometry (DXA) in wait-listed dialysis patients. Further, the circulating markers of mineral metabolism and bone turnover were compared. MATERIAL AND METHODS: Bone biopsies were performed on 61 wait-listed dialysis patients. Plasma samples were obtained for indicators of mineral metabolism and bone turnover. Bone mineral density (BMD) was determined by DXA and bone histomorphometry was performed. RESULTS: Bone histomorphometry could be determined in 52 patients (72% men, 54% on hemodialysis and median dialysis vintage 18 months). Adynamic bone disease was present in 21% of patients and 4% had osteomalacia. High turnover bone disease (mixed uremic osteodystrophy and osteitis fibrosa) was observed in 48% of patients (17% and 31%, respectively). 10% of patients had normal bone histomorphometry while 17% had mild osteitis fibrosa. Mineralization defect was found in 33% of patients. There was a strong correlation between femoral neck (FN) T-score and histologically measured cancellous bone volume (p = 0.004), FN T score having a good negative predictive value for low cancellous bone volume. Plasma osteocalcin levels were significantly higher in the high-turnover group and lower in the mineralization defect group (p = 0.014 and p = 0.02, respectively). CONCLUSIONS: Our study confirms the high frequency of abnormal bone histology in wait-listed dialysis patients. Low bone turnover was less common than previously reported. Noninvasive markers had a limited value for assessing bone histology, whereas femoral BMD reflected bone volume well. PMID- 26833299 TI - Effects of renal care coordinator case management on outcomes in incident dialysis patients. AB - BACKGROUND: Pre-dialysis chronic kidney disease (CKD) care impacts dialysis start and incident dialysis outcomes. We describe the use of late stage CKD population data coupled with CKD case management to improve dialysis start. METHODS: The Renal Care Coordinator (RCC) program is a nephrology practice and Fresenius Medical Care North America (FMCNA) partnership involving a case manager resource and data analytics. We studied patients starting dialysis between August 1, 2009 and February 28, 2013 in 9 nephrology practices partnering in the RCC program. Propensity score matching (PSM) was used to match patients who had participated in the RCC program to patients who had not. Primary outcomes were use of a permanent access or peritoneal dialysis (PD) at first outpatient dialysis. Serum albumin at the first outpatient dialysis treatment and mortality and hospitalization rates in the first 120 days of dialysis were secondary outcomes. RESULTS: In the nephrology practices studied, 7,626 patients started dialysis. Of these, 738 patients (9.7%) were enrolled in the RCC program; 693 RCC patients (93.9%) were matched with 693 patients who did not participate in the RCC program. Logistic regression analysis indicates that RCC program patients are more likely to start PD or use a permanent vascular access at dialysis start and are more likely to start treatment with a serum albumin level >= 4.0 g/ dL. CONCLUSION: Late stage CKD data-driven case management is associated with a higher rate of PD use, lower central venous catheter (CVC) use, and higher albumin levels at first outpatient dialysis. PMID- 26833300 TI - Fibroblast growth factor 23 is associated with left ventricular hypertrophy, not with uremic vasculopathy in peritoneal dialysis patients. AB - AIMS: Cardiovascular (CV) events are the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD), including those patients on peritoneal dialysis (PD). Fibroblast growth factor 23 (FGF23) has been associated with left ventricular hypertrophy (LVH) and mortality in patients with CKD. However, the role of FGF23 in uremic vasculopathy remains unclear. In this study, we aimed to assess the relationship between FGF23 and LVH, endothelial dysfunction, vascular calcification, and arterial stiffness in 48 stable PD patients. METHODS: Left ventricular mass index (LVMI) was assessed using 2-D echocardiography. Intact FGF23 blood levels were evaluated using an ELISA kit (Immutopics, Inc., San Clemente, CA, USA). Reactive hyperemia index (RHI) is a surrogate marker of endothelial dysfunction and the augmentation index (AI) is a surrogate marker of arterial stiffness. Both were assessed using peripheral arterial tonometry (EndoPAT 2000). Vascular calcification (VC) was assessed using the Adragao score. RESULTS: In unadjusted analysis; FGF23 was positively correlated with serum Pi (r = 0.487, p < 0.001), serum urea (r = 0.351, p = 0.015), serum creatinine (r = 0.535, p < 0.001), dialysis vintage (r = 0.309, p = 0.033), and LVMI (r = 0.369, p = 0.027) and was negatively correlated with age (r = -0.343, p = 0.017), residual renal function (r = -0.359, p < 0.012), and AI (r = -0.304, p = 0.038). In multivariate adjusted analysis, FGF23 was associated with LVMI (beta = 0.298, p = 0.041), serum Pi (beta = 0.345, p = 0.018), and age (beta = -0.372, p = 0.007) independent of dialysis vintage, gender, residual renal function (RRF), albumin, C-reactive protein and systolic blood pressure. There were no associations found between FGF23 and RHI, AI, or VC in multivariable- adjusted models. CONCLUSIONS: Our results show that FGF23 is associated with LVH but not with endothelial dysfunction, arterial stiffness, or vascular calcification in PD patients. PMID- 26833301 TI - Postinfectious glomerulonephritis secondary to Erythrovirus B19 (Parvovirus B19): case report and review of the literature. AB - A previously healthy 32-yearold woman developed arterial hypertension, proteinuria, and hematuria (nephritic syndrome) with normal renal function and was diagnosed with post-infectious glomerulonephritis secondary to parvovirus B19 infection. The renal biopsy showed endocapillary glomerulonephritis, with positive IgG, C3, and C1q immunoreactivity in the capillary walls and ultrastructural evidence of subendothelial deposits. The diagnosis of parvovirus B19 infection was confirmed by IgG/IgM serological positivity and parvovirus DNA demonstration in both peripheral blood and kidney tissue. Glomerular involvement improved spontaneously. To be noted are the atypical signs and symptoms of our patient who, unlike previously reported cases, failed to show fever, skin rash, or affected relatives. PMID- 26833302 TI - Safety and tolerability of Tilt Testing and Carotid Sinus Massage in the octogenarians. AB - OBJECTIVE: to evaluate the safety and tolerability of Tilt Testing (TT) and Carotid Sinus Massage (CSM) in octogenarians with unexplained syncope. METHODS: patients consecutively referred for transient loss of consciousness to the 'Syncope Units' of three hospitals were enrolled. TT and CSM were performed according to the European Society of Cardiology guidelines on syncope. Complications were evaluated in each group. An early interruption of TT was defined as 'intolerance' and considered as a non-diagnostic response. RESULTS: one thousand four hundred and one patients were enrolled (mean age 72 +/- 16 years, male 40.8%). Six hundred and ninety-four patients (49.5%) were 80 years old or older (mean age 83 +/- 3 years) and 707 (50.5%) were younger (mean age 60 +/- 17 years). Complications after TT occurred in 4.5% of older patients and in 2.1% of the younger ones (P = 0.01). All complications were 'minor/moderate', as prolonged hypotension, observed in ~3% of patients >=80 years. Major complications such as sustained ventricular tachycardia, ventricular fibrillation, asystole requiring cardiac massage, transient ischaemic attack, stroke and death were not observed in any patient. The presence of orthostatic hypotension and the mean number of syncopal episodes were predictors of TT complications. Intolerance was reported in 2.4% of older patients and 1% of the younger ones (P = 0.08), mainly due to orthostatic intolerance. No complications occurred after CSM. CONCLUSIONS: TT and CSM appear to be safe and well tolerated in octogenarians, who should not be excluded by age from the diagnostic work-up of syncope. PMID- 26833303 TI - Usability and Acceptability of the Abatacept Pre-Filled Autoinjector for the Subcutaneous Treatment of Rheumatoid Arthritis. AB - INTRODUCTION: The purpose of the present study was to determine whether the abatacept autoinjector can be used by the intended population without patterns of preventable use errors, and is acceptable when assessed against key user needs. METHODS: Two independently conducted simulated-use studies, with no active drug administered, quantified use errors and evaluated the abatacept autoinjector and competitor devices on key attributes (comfort, control, ease of use, confidence of dose) and overall acceptability. Autoinjector preference was also assessed. Participants were patients with rheumatoid arthritis, caregivers, and healthcare professionals (HCPs). Participants were informed that a new rheumatoid arthritis autoinjector was being tested but were blinded to the intended drug and sponsor identity. RESULTS: In the formative (pre-validation) study (n = 54), two high priority use errors occurred, both of which resulted from protocol non-compliance rather than mental confusion or physical limitations. In the summative (validation) study (n = 99), one high-priority use error occurred; this was deemed a simulated-use study artifact as participant behavior was guided by actual experience associated with the feel of drug delivery into the skin rather than by protocol, so no mitigation steps were considered necessary. Across user groups, average scores were consistently high for the pre-defined key attributes. Overall acceptability scores (7-point scale) were significantly higher for the abatacept versus competitor autoinjectors-formative study: patients 6.7 vs 5.2 (P = 0.0001), caregivers 7.0 vs 4.6 (P = 0.0093), HCPs 6.8 vs 5.1 (P = 0.0020); summative study: patients 6.5 vs 5.9 (P = 0.0404), caregivers 6.8 vs 5.8 (P = 0.0047), HCPs 6.8 vs 5.1 (P = 0.0002). The abatacept autoinjector was preferred to competitor devices: patients 85.7% vs 14.3% (P = 0.00002), caregivers 84.2% vs 15.8% (P = 0.00443), HCPs 95.0% vs 5.0% (P = 0.00004). Positive experiences with the abatacept autoinjector were attributed to the rubberized grip, device size, visualization of dose progression, button ergonomics, and ease of use. CONCLUSION: The abatacept autoinjector demonstrated usability without patterns of preventable use errors, and with high acceptability ratings across all key attributes assessed. Preference over competitor autoinjectors was due to device ergonomics, visualization of dose progression, confidence of dose delivery, and overall ease of use. FUNDING: Bristol-Myers Squibb. PMID- 26833305 TI - Effect of Plasma Sterilization on the Hemostatic Efficacy of a Chitosan Hemostatic Agent in a Rat Model. AB - INTRODUCTION: The United States military has had success with chitosan (CS)-based hemostatic agents to control trauma-induced hemorrhages. Despite the positive reviews, additional physical forms of CS may enhance its hemostatic efficacy. Additionally, standard sterilization techniques may negatively affect the hemostatic efficacy of CS. We studied the effects of a CS-based hemostatic pad, the Clo-Sur P.A.D.TM (Scion Cardio-Vascular, Inc.), on severe femoral vessel bleeding in a rat model. The effects of different sterilization techniques on the bioadhesivity, surface atomic concentrations, and hemostatic efficacy of the P.A.D. were also evaluated. METHODS: Hemostatic efficacy, bioadhesivity, and surface atomic concentrations of the P.A.D. were evaluated in its unsterilized form, after sterilization with standard e-beam treatment, and after sterilization with one of three types of non-thermal nitrogen plasma: nitrogen gas, air, or nitrous oxide plasma. After standardized puncture of the femoral artery or transection of the femoral vessels, rats were treated with either a CS P.A.D. or gauze pad. RESULTS: The Clo-Sur P.A.D., regardless of sterilization technique, stopped arterial and mixed arterial/venous bleeding in all cases in <90 s with the time to hemostasis (TTH) significantly less for all P.A.D. treatment groups (P < 0.001; n = 4-5/group) compared to gauze-treated controls (n = 3). E-beam sterilized P.A.D.s consistently showed non-significant trends toward increased TTH and worse hemostasis scores compared to unsterilized and plasma sterilized P.A.D.s. Treating e-beam sterilized P.A.D.s with N2 plasma reverted the hemostatic efficacy to levels equivalent to native, unsterilized PADs. CONCLUSION: A CS-based hemostatic pad successfully controlled severe bleeding in a rat model with combined e-beam and plasma sterilized P.A.D.s showing the most promising results. Further studies are warranted. PMID- 26833304 TI - Assessing Changes in Chronic Spontaneous/Idiopathic Urticaria: Comparisons of Patient-Reported Outcomes Using Latent Growth Modeling. AB - INTRODUCTION: Assessing the consequences of chronic spontaneous/idiopathic urticaria (CSU) requires the evaluation of health-related quality of life (HRQoL) associated with the severity of CSU signs and symptoms. It is important to understand how signs, symptoms, and HRQoL change over time in CSU. Evidence is lacking on how closely changes in signs and symptoms of CSU are related to changes in HRQoL. The objective of this study was to assess the correlation between changes in patient-reported outcome measures (PROMs) of signs and symptoms, dermatologic quality of life (QoL), and urticaria-specific QoL. METHODS: Latent growth models (LGMs) were applied to longitudinal data from three randomized, Phase 3 clinical trials investigating the efficacy and safety of omalizumab in CSU. RESULTS: A near-perfect association between changes in signs and symptoms and changes in dermatologic and urticaria-specific QoLs was identified in each clinical trial when using LGMs (correlation coefficient range 0.88-0.92). CONCLUSION: Evidence showed that changes in signs and symptoms are closely related to changes in HRQoL. However, analyses were performed on clinical trial results of an extremely effective treatment; a less effective treatment with much smaller changes over time may not show such close correlations. Results suggest that any of these PROMs may be used to understand changes in CSU. PMID- 26833306 TI - Reluctance to seek professional help among suicidal people: results from the Swiss Health Survey. AB - OBJECTIVES: To investigate whether help-negation (not accepting or accessing available helping resources) among suicidal people can also be found in a Swiss sample. METHODS: Data on 16,640 participants (aged 15 and older) from the Swiss Health Survey 2012 was analyzed. Logistic regression analyses were conducted to study the association between suicidality (categorized into "not at all"; "several days"; and "more than half of the days") and currently being in treatment for depression (covariates: depression and socio-demographic variables). RESULTS: Less than 1/3 of the participants with the highest level of suicidality were currently in treatment (males: 27.0 %; females: 29.6 %). Participants who were experiencing suicidality for several days were more likely to be in treatment relative to non-suicidal people. However, people with the highest level of suicidality did not differ from the other two groups in regard to treatment frequency. Help-negation was particularly pronounced among males and young people (15-24-year olds). CONCLUSIONS: The reluctance to seek professional help is problematic because treatment might reduce the risk of suicide. PMID- 26833307 TI - Use of electronic nicotine delivery systems and recent initiation of smoking among US youth. AB - OBJECTIVES: We assessed whether the prevalence of recent (within a year) initiation of cigarette smoking was associated with reports of ever using electronic delivery systems (ENDS) in the National Youth Tobacco Survey (NYTS) and whether the association varied by age. METHODS: Weighted cross-sectional analysis of use of ENDS, cigarette smoking, age at interview and age at initiation of smoking collected systematically through the 2011-2013 NYTS cycles. RESULTS: In multivariate analyses those who ever used ENDS were twice as likely as nonusers of ENDS to have tried cigarette smoking in the last year (multivariate PR: 2.3; 95 % CI 1.9, 2.7). This average hid significant variations by age: a 4.1-fold increase (95 %; 2.6, 6.4) among those 11-13 years of age, compared to a smaller increase among those 16-18 years: 1.4-fold (95 % CI 1.1, 1.8). CONCLUSIONS: Use of ENDS by adolescents was associated with initiation of cigarette smoking in the last year. This association was stronger in younger adolescents. PMID- 26833309 TI - A new partnership for an impactful future. PMID- 26833308 TI - GSIV serine/threonine kinase can induce apoptotic cell death via p53 and pro apoptotic gene Bax upregulation in fish cells. AB - Previous studies have shown that GSIV induces apoptotic cell death through upregulation of the pro-apoptotic genes Bax and Bak in Grouper fin cells (GF-1 cells). However, the role of viral genome-encoded protein(s) in this death process remains unknown. In this study, we demonstrated that the Giant seaperch iridovirus (GSIV) genome encoded a serine/threonine kinase (ST kinase) protein, and induced apoptotic cell death via a p53-mediated Bax upregulation approach and a downregulation of Bcl-2 in fish cells. The ST kinase expression profile was identified through Western blot analyses, which indicated that expression started at day 1 h post-infection (PI), increased up to day 3, and then decreased by day 5 PI. This profile indicated the role of ST kinase expression during the early and middle phases of viral replication. We then cloned the ST kinase gene and tested its function in fish cells. The ST kinase was transiently expressed and used to investigate possible novel protein functions. The transient expression of ST kinase in GF-1 cells resulted in apoptotic cell features, as revealed with Terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL) assays and Hoechst 33258 staining at 24 h (37 %) and 48 h post-transfection (PT) (49 %). Then, through studies on the mechanism of cell death, we found that ST kinase overexpression could upregulate the anti-stress gene p53 and the pro apoptotic gene Bax at 48 h PT. Interestingly, this upregulation of p53 and Bax also correlated to alterations in the mitochondria function that induced loss of mitochondrial membrane potential (MMP) and activated the initiator caspase-9 and the effector caspase-3 in the downstream. Moreover, when the p53-dependent transcriptional downstream gene was blocked by a specific transcriptional inhibitor, it was found that pifithrin-alpha not only reduced Bax expression, but also averted cell death in GF-1 cells during the ST kinase overexpression. Taken altogether, these results suggested that aquatic GSIV ST kinase could induce apoptosis via upregulation of p53 and Bax expression, resulting in mitochondrial disruption, which activated a downstream caspases-mediated cell death pathway. PMID- 26833310 TI - Profile of Xiaofeng Cao. PMID- 26833312 TI - Pyeloplasty in children: perioperative results and long-term outcomes of robotic assisted laparoscopic surgery compared to open surgery. AB - BACKGROUND: A few studies have compared robotic-assisted laparoscopic pyeloplasty (RALP) with open pyeloplasty (OP) in children, but no previous study includes a long-term follow-up of renal function and hydronephrosis in combination with a thorough prospective follow-up of the RALP patients of at least 2 years. OBJECTIVE: To analyze perioperative results and long-term outcome of children with obstruction of the ureteropelvic junction, operated on with RALP compared to OP. PATIENTS AND METHODS: Children <=15 years operated on with RALP or OP from 2000 through 2013 were reviewed. Patient demographics, perioperative data, postoperative complications, and long-term outcome were evaluated. The outcome was based on pre- and postoperative examination of renal function, hydronephrosis and flank pain. RESULTS: 129 pyeloplasties (84 OP, 39 RALP, 6 reoperations) on 123 patients were included. RALP had significantly longer operative time and shorter postoperative hospital stay, compared to OP. No difference was found in postoperative need of morphine or complication rates. Mean follow-up for RALP with ultrasound was 29 and 25 months with renal scan, compared to 34 and 28 months, respectively, for OP. The success rate for flank pain was 96 and 94 %, for hydronephrosis 93 and 95 %, and renal function 94 and 92 %, for RALP and OP, respectively. CONCLUSIONS: RALP is a safe method, with advantages compared to OP, and with the same success rate. This study supports the use of RALP in children. PMID- 26833313 TI - The mid-term outcomes of TRM-PIAS, proctocolectomy and ileoanal anastomosis for total colonic aganglionosis. AB - AIMS: The present study aimed to evaluate the mid-term outcomes of total colonic aganglionosis (TCA) after transanal rectal mucosectomy and partial internal anal sphincterectomy (TRM-PIAS), proctocolectomy and ileoanal anastomosis. PATIENTS AND METHODS: From 2012 to 2014, 12 patients (7 boys; 58.3 %) diagnosed with TCA and treated with the TRM-PIAS, proctocolectomy and ileoanal anastomosis. Seven TCA patients who underwent laparotomy-assisted endorectal pull-through (LEPT) between 2010 and 2012 were used as control group. Demographic features and complication of the two groups were evaluated. The functional outcomes were assessed by using a score system. RESULTS: The procedure was successfully performed in all patients. The incidence of postoperative HAEC in the TRM-PIAS group was significantly lower (25.0 vs 85.7 %; p < 0.05) than control group within the second postoperative year. The number of bowel movement after 3, 12 and 24 months postoperatively, was 8.5 +/- 3.5, 5.3 +/- 2.9 and 3.1 +/- 1.4 (p < 0.05) per day, respectively, in the TRM-PIAS group. The soiling was noted in 50.0 % (n = 6) of the patients in the 6th postoperative month, and 25.0 % (n = 3) in the 24th postoperative month in the TRM-PIAS group. There was no significant difference in overall functional outcome between two groups, but the TRM-PIAS group was better in terms of bowel movement and soiling. CONCLUSION: TRM-PIAS, proctocolectomy and ileoanal anastomosis might be an effective treatment for TCA. More prospective studies evaluating the TRM-PIAS technique over longer period and with greater sample size are needed to confirm the findings in this study. PMID- 26833315 TI - Rapid apprehension of the coherence of action scenes. AB - Some information about complex naturalistic scenes, such as the scene's gist (a beach, a restaurant) or the category of an object depicted in a scene, can be extracted within a fraction of a second. The present study focused on the rapid apprehension of scene coherence in action scenes involving two actors. Coherence was manipulated by either varying global (body posture) or local (object details) action-scene properties. Scenes were presented for 20, 30, 50, or 100 ms, and subsequently masked. Viewers were able to determine scene coherence with only 30 ms presentation duration for global scene layout, but not even 100 ms sufficed for local object-action consistency. A second experiment ruled out that the difficulties in detecting local object-action consistency resulted from a strategic adaption by the participants. Overall, the results suggest that, as with scene gist, rapid extraction of coherence information from action scenes relies more on a scene's overall Gestalt than on detailed visual or even semantic representations. PMID- 26833316 TI - Is neuroimaging measuring information in the brain? AB - Psychology moved beyond the stimulus response mapping of behaviorism by adopting an information processing framework. This shift from behavioral to cognitive science was partly inspired by work demonstrating that the concept of information could be defined and quantified (Shannon, 1948). This transition developed further from cognitive science into cognitive neuroscience, in an attempt to measure information in the brain. In the cognitive neurosciences, however, the term information is often used without a clear definition. This paper will argue that, if the formulation proposed by Shannon is applied to modern neuroimaging, then numerous results would be interpreted differently. More specifically, we argue that much modern cognitive neuroscience implicitly focuses on the question of how we can interpret the activations we record in the brain (experimenter-as receiver), rather than on the core question of how the rest of the brain can interpret those activations (cortex-as-receiver). A clearer focus on whether activations recorded via neuroimaging can actually act as information in the brain would not only change how findings are interpreted but should also change the direction of empirical research in cognitive neuroscience. PMID- 26833317 TI - Face-name learning in older adults: a benefit of hyper-binding. AB - Difficulty remembering faces and corresponding names is a hallmark of cognitive aging, as is increased susceptibility to distraction. Given evidence that older adults spontaneously encode relationships between target pictures and simultaneously occurring distractors (a hyper-binding phenomenon), we asked whether memory for face-name pairs could be improved through prior exposure to faces presented with distractor names. In three experiments, young and older adults performed a selective attention task on faces while ignoring superimposed names. After a delay, they learned and were tested on face-name pairs that were either maintained or rearranged from the initial task but were not told of the connection between tasks. In each experiment, older but not younger participants showed better memory for maintained than for rearranged pairs, indicating that older adults' natural propensity to tacitly encode and bind relevant and irrelevant information can be employed to aid face-name memory performance. PMID- 26833314 TI - Optimizing performance through intrinsic motivation and attention for learning: The OPTIMAL theory of motor learning. AB - Effective motor performance is important for surviving and thriving, and skilled movement is critical in many activities. Much theorizing over the past few decades has focused on how certain practice conditions affect the processing of task-related information to affect learning. Yet, existing theoretical perspectives do not accommodate significant recent lines of evidence demonstrating motivational and attentional effects on performance and learning. These include research on (a) conditions that enhance expectancies for future performance, (b) variables that influence learners' autonomy, and (c) an external focus of attention on the intended movement effect. We propose the OPTIMAL (Optimizing Performance through Intrinsic Motivation and Attention for Learning) theory of motor learning. We suggest that motivational and attentional factors contribute to performance and learning by strengthening the coupling of goals to actions. We provide explanations for the performance and learning advantages of these variables on psychological and neuroscientific grounds. We describe a plausible mechanism for expectancy effects rooted in responses of dopamine to the anticipation of positive experience and temporally associated with skill practice. Learner autonomy acts perhaps largely through an enhanced expectancy pathway. Furthermore, we consider the influence of an external focus for the establishment of efficient functional connections across brain networks that subserve skilled movement. We speculate that enhanced expectancies and an external focus propel performers' cognitive and motor systems in productive "forward" directions and prevent "backsliding" into self- and non-task focused states. Expected success presumably breeds further success and helps consolidate memories. We discuss practical implications and future research directions. PMID- 26833319 TI - Pathophysiological mechanism and therapeutic role of S100 proteins in cardiac failure: a systematic review. AB - S100 proteins are a family of highly acidic calcium-binding proteins involved in calcium handling in many tissues and organs. Some of these proteins are highly expressed in cardiac tissue, and an impairment of some specific S100 proteins has been related to heart failure. To check this hypothesis, we decided to review the literature since 2008 until May 2015. According to the studies collected, recovering S100A1 levels may enhance contractile/relaxing performance in heart failure, reverse negative force-frequency relationship, improve contractile reserve, reverse diastolic dysfunction and protect against pro-arrhythmic reductions of sarcoplasmic reticulum calcium. The safety profile of gene therapy was also confirmed. Increased S100B protein levels were related to a worse outcome in chronic heart failure. S100A8/A9 complex plasma levels, as well as other inflammatory biomarkers, were significantly higher in chronic heart failure patients. S100A2 seems to increase both contractile and relaxation performance in animal cardiomyocytes. Otherwise, S100A6 cardiac expression seems to have no effects on contractility. S100A4 KO mice showed reduced cardiac interstitial fibrosis. Data collected encourage a potential prospective application in human. These proteins could be exploited as biomarkers in stadiation and prognosis of chronic heart failure, as well as therapeutic target to rescue failing heart. Registration details The study protocol has been registered in PROSPERO ( http://www.crd.york.ac.uk/PROSPERO/ ) under registration number CRD42015027932. PMID- 26833318 TI - The right ventricle and pulmonary hypertension. AB - In patients with pulmonary hypertension (PH), the primary cause of death is right ventricular (RV) failure. Improvement in RV function is therefore one of the most important treatment goals. In order to be able to reverse RV dysfunction and also prevent RV failure, a detailed understanding of the pathobiology of RV failure and the underlying mechanisms concerning the transition from a pressure overloaded adapted right ventricle to a dilated and failing right ventricle is required. Here, we propose that insufficient RV contractility, myocardial fibrosis, capillary rarefaction, and a disturbed metabolism are important features of a failing right ventricle. Furthermore, an overview is provided about the potential direct RV effects of PH-targeted therapies and the effects of RV directed medical treatments. PMID- 26833320 TI - Personalised computational cardiology: Patient-specific modelling in cardiac mechanics and biomaterial injection therapies for myocardial infarction. AB - Predictive computational modelling in biomedical research offers the potential to integrate diverse data, uncover biological mechanisms that are not easily accessible through experimental methods and expose gaps in knowledge requiring further research. Recent developments in computing and diagnostic technologies have initiated the advancement of computational models in terms of complexity and specificity. Consequently, computational modelling can increasingly be utilised as enabling and complementing modality in the clinic-with medical decisions and interventions being personalised. Myocardial infarction and heart failure are amongst the leading causes of death globally despite optimal modern treatment. The development of novel MI therapies is challenging and may be greatly facilitated through predictive modelling. Here, we review the advances in patient specific modelling of cardiac mechanics, distinguishing specificity in cardiac geometry, myofibre architecture and mechanical tissue properties. Thereafter, the focus narrows to the mechanics of the infarcted heart and treatment of myocardial infarction with particular attention on intramyocardial biomaterial delivery. PMID- 26833322 TI - Analysis of the immune response of a new malaria vaccine based on the modification of cryptic epitopes. AB - Malaria is a severe, life-threatening infectious disease that endangers human health. However, there are no vaccines or immune strategy of vaccines succeeding in both erythrocytic and pre-erythrocytic stage. During the liver stage of the Plasmodium life cycle, sporozoites invade the host liver cells. The sporozoites, then, induce a cellular immune response via the major histocompatibility complex (MHC) molecules on their surfaces. The cytotoxic T lymphocytes (CTLs) then recognize the corresponding antigen-MHC complex on the surfaces of these infected liver cells and kill them. However, dominant epitopes with high MHC affinity are prone to mutation due to immune selection pressure. CTLs evoked by the original dominant epitopes cannot recognize the mutated epitopes, leading to immune evasion. In this study, we have modified the cryptic epitopes of different antigens in the sporozoite and liver stages of Plasmodium falciparum to increase their immunogenicity without changing T cell antigen receptor (TCR)-peptide binding specificity. In addition, we have also added an important erythrocytic phase protective antigen, named apical membrane antigen 1 (AMA-1), to this process with the goal of constructing a complex multi-stage, multi-epitope recombinant DNA vaccine against P. falciparum. The vaccine was tested in HHD-2 mice. The method involved multiple stages of the P. falciparum life cycle as well as elucidation both humoral and cellular immunity. The conclusion drawn from the study was that the vaccine might provide an important theoretical and practical basis for generating effective preventative or therapeutic vaccine against P. falciparum. PMID- 26833321 TI - Novel Cardiac Magnetic Resonance Feature Tracking (CMR-FT) Analysis for Detection of Myocardial Fibrosis in Pediatric Hypertrophic Cardiomyopathy. AB - Myocardial fibrosis is a risk factor for sudden cardiac death in hypertrophic cardiomyopathy (HCM) and is conventionally identified by cardiac magnetic resonance imaging (CMR) using late gadolinium enhancement (LGE). This study evaluates utility of a novel 16-segment CMR feature tracking (CMR-FT) technique for measuring left ventricular (LV) strain (S) and strain rate (SR) on non contrast cine images to detect myocardial fibrosis in pediatric HCM. We hypothesized that CMR-FT-derived S and SR will accurately differentiate HCM patients with and without myocardial fibrosis. Consecutive children with HCM who underwent CMR with LGE at our institution from 2006 to 2014 were included. Global and regional longitudinal, radial and circumferential S and SR of the LV in 2D and 3D were obtained using a CMR-FT software. Comparisons were made between HCM patients with (+LGE) and without (-LGE) delayed enhancement. Of the 29 HCM patients (mean age 13.5 +/- 6.1 years; 52 % males), 11 (40 %) patients (mean age 17.5 +/- 8.4 years) had +LGE. Global longitudinal, circumferential and radial S and SR were lower in +LGE compared to -LGE patients, in both 2D and 3D. Regional analysis revealed lower segmental S and SR in the septum with fibrosis compared to free wall without fibrosis. A global longitudinal S of <= -12.8 had 91 % sensitivity and 89 % specificity for detection of LGE. In pediatric HCM patients with myocardial fibrosis, global LV longitudinal, circumferential and radial S and SR were reduced, specifically in areas of fibrosis. A global longitudinal S of <= -12.8 detected patients with fibrosis with high degree of accuracy. This novel CMR-FT technique may be useful to identify myocardial fibrosis and risk stratify pediatric HCM without use of contrast agents. PMID- 26833323 TI - Identification and characterization of Theileria ovis surface protein (ToSp) resembled TaSp in Theileria annulata. AB - Ovine theileriosis is an important hemoprotozoal disease of sheep and goats in tropical and subtropical regions which caused high economic loses in the livestock industry. Theileria annulata surface protein (TaSp) was used previously as a tool for serological analysis in livestock. Since the amino acid sequences of TaSp is, at least, in part very conserved in T. annulata, Theileria lestoquardi and Theileria china I and II, it is very important to determine the amino acid sequence of this protein in Theileria ovis as well, to avoid false interpretation of serological data based on this protein in small animal. In the present study, the nucleotide sequence and amino acid sequence of T. ovis surface protein (ToSp) were determined. The comparison of the nucleotide sequence of ToSp showed 96, 96, 99, and 86 % homology to the corresponding nucleotide sequence of TaSp genes by T. annulata, T. China I, T. China II and T. lestoquardi, previously registered in GenBank under accession nos. AJ316260.1, AY274329.1, DQ120058.1, and EF092924.1 respectively. The amino acid sequence analysis showed 95, 81, 98 and 70 % homology to the corresponding amino acid sequence of T. annulata, T chinaI, T china II and T. lestoquardi, registered in GenBank under accession nos. CAC87478.1, AAP36993.1, AAZ30365.1 and AAP36999.11, respectively. Interestingly, in contrast to the C terminus, a significant difference in amino acid sequence in the N teminus of the ToSp protein could be determined compared to the other known corresponding TaSp sequences, which make this region attractive for designing of a suitable tool for serological diagnosis. PMID- 26833324 TI - An updated distribution and hosts: trombiculid mites (Acari: Trombidiformes) associated with small mammals in Yunnan Province, southwest China. AB - Trombiculid mites (or chigger mites) are a large group of arthropods, and some of these species are vectors of Orientia tsutsugamushi, the causative agent of tsutsugamushi disease (scrub typhus). Yunnan Province is situated in the southwest of China, and its complicated topography, special altitude gradients, and high biodiversity have aroused the interest of many scientists to study the fauna and species diversity of plants and animals. To replenish our former faunal study, this paper listed all the scientific names of trombiculid mites in Yunnan Province, together with their hosts and collection sites (geographical distribution). A total of 120,138 individuals of trombiculid mites were collected from the body surface of 13,760 small mammal hosts (89.06 % of them are rodents) in 29 collection sites (counties) of Yunnan Province from 2001 to 2013. The 120,138 mites were identified as comprising 2 families (Trombiculidae and Leeuwenhoekiidae), 26 genera, and 274 species. The genus Leptotrombidium had the most abundant species (109 species) of 26 genera. Of the six main vectors of scrub typhus in China, five of them were found in Yunnan. Of the 274 chigger mite species, 23 were determined as the newly recorded species (new records), which were found in Yunnan Province for the first time. The identified 274 species of trombiculid mites in the present paper are much more than those from other provinces in China and even largely exceeded the species of trombiculid mites recorded from some other regions and countries in the world. Based on the formula of Chao 1, the total number of chigger mite species in Yunnan was approximately estimated to be 346 species, and about 72 species might have been missed in our sampling process. PMID- 26833325 TI - Detection of Borrelia burgdorferi sensu lato and spotted fever group rickettsiae in hard ticks (Acari, Ixodidae) parasitizing bats in Poland. AB - A total of 491 Ixodes vespertilionis and 8 Ixodes ricinus collected from bats and cave walls in southern Poland between 2010 and 2012 were examined by the polymerase chain reaction for tick-transmitted pathogens. PCR analysis for Borrelia burgdorferi s.l., Rickettsia spp., and Anaplasma phagocytophilum yielded negative results for all I. vespertilionis. DNA of Rickettsia helvetica was detected in three specimens of I. ricinus attached to Rhinolophus hipposideros or Myotis myotis, while Borrelia garinii was found in one tick parasitizing Myotis daubentonii. These pathogens were recorded for the first time in hard ticks that parasitized bats. PMID- 26833326 TI - Detection and molecular characterization of Cryptosporidium and Eimeria species in Philippine bats. AB - The genus Cryptosporidium, which is an obligate intracellular parasite, infects various vertebrates and causes a diarrheal disease known as cryptosporidiosis. Bats are naturally infected with zoonotic pathogens; thus, they are potential reservoirs of parasites. We investigated the species and genotype distribution as well as prevalence of Cryptosporidium and Eimeria in Philippine bats. We captured and examined 45 bats; four were positive for Cryptosporidium spp. and seven were positive for Eimeria spp. We detected Cryptosporidium bat genotype II from Ptenochirus jagori. Three other Cryptosporidium sequences, detected from Rhinolophus inops, Cynopterus brachyotis, and Eonycteris spelaea, could not be classified as any known species or genotype; we therefore propose the novel genotype Cryptosporidium bat genotypes V, VI, and VII. Bat genotype V is associated with human cryptosporidiosis clade, and therefore, this genotype may be transmissible to humans. Among the Eimeria sequences, BE3 detected from Scotophilus kuhlii was classified with known bat and rodent clades; however, other sequences detected from C. brachyotis, E. spelaea, Rousettus amplexicaudatus, and R. inops could not be classified with known Eimeria species. These isolates might represent a new genotype. Our findings demonstrate that the bats of the Philippines represent a reservoir of multiple Cryptosporidium and Eimeria spp. PMID- 26833327 TI - Weak value amplification: a view from quantum estimation theory that highlights what it is and what isn't. AB - Weak value amplification (WVA) is a concept that has been extensively used in a myriad of applications with the aim of rendering measurable tiny changes of a variable of interest. In spite of this, there is still an on-going debate about its true nature and whether is really needed for achieving high sensitivity. Here we aim at helping to clarify the puzzle, using a specific example and some basic concepts from quantum estimation theory, highlighting what the use of the WVA concept can offer and what it can not. While WVA cannot be used to go beyond some fundamental sensitivity limits that arise from considering the full nature of the quantum states, WVA can notwithstanding enhance the sensitivity of real and specific detection schemes that are limited by many other things apart from the quantum nature of the states involved, i.e. technical noise. Importantly, it can do that in a straightforward and easily accessible manner. PMID- 26833328 TI - De Novo Loss-of-Function Mutations in USP9X Cause a Female-Specific Recognizable Syndrome with Developmental Delay and Congenital Malformations. AB - Mutations in more than a hundred genes have been reported to cause X-linked recessive intellectual disability (ID) mainly in males. In contrast, the number of identified X-linked genes in which de novo mutations specifically cause ID in females is limited. Here, we report 17 females with de novo loss-of-function mutations in USP9X, encoding a highly conserved deubiquitinating enzyme. The females in our study have a specific phenotype that includes ID/developmental delay (DD), characteristic facial features, short stature, and distinct congenital malformations comprising choanal atresia, anal abnormalities, post axial polydactyly, heart defects, hypomastia, cleft palate/bifid uvula, progressive scoliosis, and structural brain abnormalities. Four females from our cohort were identified by targeted genetic testing because their phenotype was suggestive for USP9X mutations. In several females, pigment changes along Blaschko lines and body asymmetry were observed, which is probably related to differential (escape from) X-inactivation between tissues. Expression studies on both mRNA and protein level in affected-female-derived fibroblasts showed significant reduction of USP9X level, confirming the loss-of-function effect of the identified mutations. Given that some features of affected females are also reported in known ciliopathy syndromes, we examined the role of USP9X in the primary cilium and found that endogenous USP9X localizes along the length of the ciliary axoneme, indicating that its loss of function could indeed disrupt cilium regulated processes. Absence of dysregulated ciliary parameters in affected female-derived fibroblasts, however, points toward spatiotemporal specificity of ciliary USP9X (dys-)function. PMID- 26833329 TI - Small 6q16.1 Deletions Encompassing POU3F2 Cause Susceptibility to Obesity and Variable Developmental Delay with Intellectual Disability. AB - Genetic studies of intellectual disability and identification of monogenic causes of obesity in humans have made immense contribution toward the understanding of the brain and control of body mass. The leptin > melanocortin > SIM1 pathway is dysregulated in multiple monogenic human obesity syndromes but its downstream targets are still unknown. In ten individuals from six families, with overlapping 6q16.1 deletions, we describe a disorder of variable developmental delay, intellectual disability, and susceptibility to obesity and hyperphagia. The 6q16.1 deletions segregated with the phenotype in multiplex families and were shown to be de novo in four families, and there was dramatic phenotypic overlap among affected individuals who were independently ascertained without bias from clinical features. Analysis of the deletions revealed a ~350 kb critical region on chromosome 6q16.1 that encompasses a gene for proneuronal transcription factor POU3F2, which is important for hypothalamic development and function. Using morpholino and mutant zebrafish models, we show that POU3F2 lies downstream of SIM1 and controls oxytocin expression in the hypothalamic neuroendocrine preoptic area. We show that this finding is consistent with the expression patterns of POU3F2 and related genes in the human brain. Our work helps to further delineate the neuro-endocrine control of energy balance/body mass and demonstrates that this molecular pathway is conserved across multiple species. PMID- 26833330 TI - TMEM199 Deficiency Is a Disorder of Golgi Homeostasis Characterized by Elevated Aminotransferases, Alkaline Phosphatase, and Cholesterol and Abnormal Glycosylation. AB - Congenital disorders of glycosylation (CDGs) form a genetically and clinically heterogeneous group of diseases with aberrant protein glycosylation as a hallmark. A subgroup of CDGs can be attributed to disturbed Golgi homeostasis. However, identification of pathogenic variants is seriously complicated by the large number of proteins involved. As part of a strategy to identify human homologs of yeast proteins that are known to be involved in Golgi homeostasis, we identified uncharacterized transmembrane protein 199 (TMEM199, previously called C17orf32) as a human homolog of yeast V-ATPase assembly factor Vph2p (also known as Vma12p). Subsequently, we analyzed raw exome-sequencing data from families affected by genetically unsolved CDGs and identified four individuals with different mutations in TMEM199. The adolescent individuals presented with a mild phenotype of hepatic steatosis, elevated aminotransferases and alkaline phosphatase, and hypercholesterolemia, as well as low serum ceruloplasmin. Affected individuals showed abnormal N- and mucin-type O-glycosylation, and mass spectrometry indicated reduced incorporation of galactose and sialic acid, as seen in other Golgi homeostasis defects. Metabolic labeling of sialic acids in fibroblasts confirmed deficient Golgi glycosylation, which was restored by lentiviral transduction with wild-type TMEM199. V5-tagged TMEM199 localized with ERGIC and COPI markers in HeLa cells, and electron microscopy of a liver biopsy showed dilated organelles suggestive of the endoplasmic reticulum and Golgi apparatus. In conclusion, we have identified TMEM199 as a protein involved in Golgi homeostasis and show that TMEM199 deficiency results in a hepatic phenotype with abnormal glycosylation. PMID- 26833331 TI - Retrospective Binary-Trait Association Test Elucidates Genetic Architecture of Crohn Disease. AB - In genetic association testing, failure to properly control for population structure can lead to severely inflated type 1 error and power loss. Meanwhile, adjustment for relevant covariates is often desirable and sometimes necessary to protect against spurious association and to improve power. Many recent methods to account for population structure and covariates are based on linear mixed models (LMMs), which are primarily designed for quantitative traits. For binary traits, however, LMM is a misspecified model and can lead to deteriorated performance. We propose CARAT, a binary-trait association testing approach based on a mixed effects quasi-likelihood framework, which exploits the dichotomous nature of the trait and achieves computational efficiency through estimating equations. We show in simulation studies that CARAT consistently outperforms existing methods and maintains high power in a wide range of population structure settings and trait models. Furthermore, CARAT is based on a retrospective approach, which is robust to misspecification of the phenotype model. We apply our approach to a genome wide analysis of Crohn disease, in which we replicate association with 17 previously identified regions. Moreover, our analysis on 5p13.1, an extensively reported region of association, shows evidence for the presence of multiple independent association signals in the region. This example shows how CARAT can leverage known disease risk factors to shed light on the genetic architecture of complex traits. PMID- 26833334 TI - The effectiveness of the Ponseti method for treating clubfoot associated with arthrogryposis: up to 8 years follow-up. AB - PURPOSE: To evaluate the effectiveness of the Ponseti method in treating clubfoot associated with arthrogryposis. METHODS: Retrospective consecutive review over a 10-year period in a tertiary centre of all patients with arthrogrypotic clubfoot treated with the Ponseti method. The primary outcome measure at final follow-up was the functional correction of the deformity. RESULTS: There were ten children with 17 arthrogrypotic clubfeet, with an average follow-up of 5.8 years (range 3 8 years). The average age at presentation was 5 weeks (range 2-20 weeks). Deformities were severe, with an average Pirani score of 5.5 (range 3-6). Initial correction was achieved in all children with an average of 8 (range 4-10) Ponseti casts and a tendo-Achilles tenotomy (TAT) was performed in 94.1 %. Two-thirds of patients had a satisfactory outcome at final follow-up, with functional plantigrade, pain-free feet. CONCLUSIONS: The Ponseti method is an effective first-line treatment for arthrogrypotic clubfeet to achieve functional plantigrade feet. Children will often require more casts and have a higher risk of relapse. PMID- 26833335 TI - The influence of posterior tibial slope changes on joint gap and range of motion in unicompartmental knee arthroplasty. AB - BACKGROUND: The effect of posterior slope on joint gap in unicompartmental knee arthroplasty (UKA) has yet to be quantified. The purpose of this study was to quantify the effect of the tibial slope on the joint component gap and postoperative range of motion in UKA. METHODS: Forty consecutive patients were prospectively enrolled. The correlation between the tibial slope changes and the component gap, the component gap difference between flexion angles, the postoperative extension or flexion angles was examined. The correlation of joint looseness with tibial slope changes and postoperative extension angle was also examined. RESULTS: Increased tibial slope positively correlated with the differences between the component gap at 90 degrees and 10 degrees , 120 degrees and 10 degrees , or 135 degrees and 10 degrees knee flexion angle. Although tibial slope change did not affect postoperative flexion angle, increased tibial slope reduced postoperative extension angle. Moreover, increased tibial slope resulted in decreased joint looseness during 10 degrees of knee flexion and decreased joint looseness during 10 degrees of knee flexion resulted in reduced postoperative extension angle. CONCLUSIONS: Increased tibial slope resulted in tight component gap at knee extension compared with that at knee flexion. Furthermore, tight component gap at extension lead to decreased postoperative extension angle. These results indicate that an individual anatomical tibial slope should be considered when tibial sagittal osteotomy was performed and increasing tibial slope should be avoided to achieve full extension angle after UKA. LEVEL OF EVIDENCE: II. PMID- 26833332 TI - CCDC115 Deficiency Causes a Disorder of Golgi Homeostasis with Abnormal Protein Glycosylation. AB - Disorders of Golgi homeostasis form an emerging group of genetic defects. The highly heterogeneous clinical spectrum is not explained by our current understanding of the underlying cell-biological processes in the Golgi. Therefore, uncovering genetic defects and annotating gene function are challenging. Exome sequencing in a family with three siblings affected by abnormal Golgi glycosylation revealed a homozygous missense mutation, c.92T>C (p.Leu31Ser), in coiled-coil domain containing 115 (CCDC115), the function of which is unknown. The same mutation was identified in three unrelated families, and in one family it was compound heterozygous in combination with a heterozygous deletion of CCDC115. An additional homozygous missense mutation, c.31G>T (p.Asp11Tyr), was found in a family with two affected siblings. All individuals displayed a storage-disease-like phenotype involving hepatosplenomegaly, which regressed with age, highly elevated bone-derived alkaline phosphatase, elevated aminotransferases, and elevated cholesterol, in combination with abnormal copper metabolism and neurological symptoms. Two individuals died of liver failure, and one individual was successfully treated by liver transplantation. Abnormal N- and mucin type O-glycosylation was found on serum proteins, and reduced metabolic labeling of sialic acids was found in fibroblasts, which was restored after complementation with wild-type CCDC115. PSI-BLAST homology detection revealed reciprocal homology with Vma22p, the yeast V-ATPase assembly factor located in the endoplasmic reticulum (ER). Human CCDC115 mainly localized to the ERGIC and to COPI vesicles, but not to the ER. These data, in combination with the phenotypic spectrum, which is distinct from that associated with defects in V ATPase core subunits, suggest a more general role for CCDC115 in Golgi trafficking. Our study reveals CCDC115 deficiency as a disorder of Golgi homeostasis that can be readily identified via screening for abnormal glycosylation in plasma. PMID- 26833337 TI - Reply. PMID- 26833333 TI - Whole-Genome Sequencing Reveals Diverse Models of Structural Variations in Esophageal Squamous Cell Carcinoma. AB - Comprehensive identification of somatic structural variations (SVs) and understanding their mutational mechanisms in cancer might contribute to understanding biological differences and help to identify new therapeutic targets. Unfortunately, characterization of complex SVs across the whole genome and the mutational mechanisms underlying esophageal squamous cell carcinoma (ESCC) is largely unclear. To define a comprehensive catalog of somatic SVs, affected target genes, and their underlying mechanisms in ESCC, we re-analyzed whole-genome sequencing (WGS) data from 31 ESCCs using Meerkat algorithm to predict somatic SVs and Patchwork to determine copy-number changes. We found deletions and translocations with NHEJ and alt-EJ signature as the dominant SV types, and 16% of deletions were complex deletions. SVs frequently led to disruption of cancer-associated genes (e.g., CDKN2A and NOTCH1) with different mutational mechanisms. Moreover, chromothripsis, kataegis, and breakage-fusion bridge (BFB) were identified as contributing to locally mis-arranged chromosomes that occurred in 55% of ESCCs. These genomic catastrophes led to amplification of oncogene through chromothripsis-derived double-minute chromosome formation (e.g., FGFR1 and LETM2) or BFB-affected chromosomes (e.g., CCND1, EGFR, ERBB2, MMPs, and MYC), with approximately 30% of ESCCs harboring BFB-derived CCND1 amplification. Furthermore, analyses of copy-number alterations reveal high frequency of whole genome duplication (WGD) and recurrent focal amplification of CDCA7 that might act as a potential oncogene in ESCC. Our findings reveal molecular defects such as chromothripsis and BFB in malignant transformation of ESCCs and demonstrate diverse models of SVs-derived target genes in ESCCs. These genome-wide SV profiles and their underlying mechanisms provide preventive, diagnostic, and therapeutic implications for ESCCs. PMID- 26833336 TI - Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms for HIV 1 Prevention: A Randomized Trial. AB - BACKGROUND: A prophylactic HIV-1 vaccine is a global health priority. OBJECTIVE: To assess a novel vaccine platform as a prophylactic HIV-1 regimen. DESIGN: Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149). SETTING: United States, East Africa, and South Africa. PATIENTS: Healthy adults without HIV infection. INTERVENTION: 2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 * 1010 viral particles) in homologous and heterologous combinations. MEASUREMENTS: Safety and immunogenicity and the effect of baseline vector immunity. RESULTS: 217 participants received at least 1 vaccination, and 210 (>96%) completed follow up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30-300 to 3000). The heterologous regimen of Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States. LIMITATIONS: Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown. CONCLUSION: Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response. PRIMARY FUNDING SOURCE: International AIDS Vaccine Initiative, National Institutes of Health, Ragon Institute, Crucell Holland. PMID- 26833338 TI - Mechanical Dispersion Assessed by Strain Echocardiography Is Associated with Malignant Arrhythmias in Chagas Cardiomyopathy. AB - BACKGROUND: Sudden death is one of the characteristics of Chagas disease (ChD). With the development of strategies for the prevention of malignant arrhythmias, especially with implantable cardioverter-defibrillators (ICDs), there is interest in developing strategies to predict sudden cardiac death. The aim of this study was to test the hypothesis that global longitudinal strain (GLS) and mechanical dispersion (MD) may be associated with malignant ventricular arrhythmias in patients with ChD. METHODS: A cross-sectional study was conducted including 62 patients with ChD who were separated into two groups according to ICD implantation status. Group 0 consisted of 34 patients with ChD without ICDs, and group 1 comprised 28 patients with ICDs. Complete echocardiographic studies, including GLS and MD measurements, were performed in all patients. RESULTS: Chamber dimensions, ejection fraction, and diastolic function showed no significant differences between patients with and those without ICDs. GLS was reduced in patients with ChD with ICDs compared with those without (P = .02). By receiver operating characteristic curve analyses, GLS identified patients with ChD with ICDs with sensitivity of 67% and specificity of 69%. MD was more pronounced in patients with ChD with ICDs compared with those without (P < .001), with a C statistic of 0.83 (95% CI, 0.71-0.91). MD > 57 msec detected ICD presence with sensitivity of 79% and specificity of 71% and was superior to GLS and ejection fraction (P < .05). In multivariate analysis, New York Heart Association functional class (odds ratio, 3.02; 95% CI, 1.09-8.39; P = .03), MD (odds ratio, 1.11; 95% CI, 1.04-1.19; P = .001), and GLS (odds ratio, 0.72; 95% CI, 0.54-0.96; P = .026) were significant and independently associated with malignant arrhythmic events. CONCLUSIONS: GLS and MD may add important information in the risk stratification of patients with ChD. The use of MD by strain echocardiography could be an attractive tool in the decision making for ICD placement as primary prevention for sudden cardiac death in patients with ChD. PMID- 26833339 TI - Psycho-social resilience, vulnerability and suicide prevention: impact evaluation of a mentoring approach to modify suicide risk for remote Indigenous Australian students at boarding school. AB - BACKGROUND: The proposed study was developed in response to increased suicide risk identified in Aboriginal and Torres Strait Islander students who are compelled to attend boarding schools across Queensland when there is no secondary schooling provision in their remote home communities. It will investigate the impact of a multicomponent mentoring intervention to increase levels of psychosocial resilience. We aim to test the null hypothesis that students' resilience is not positively influenced by the intervention. The 5-year project was funded by the Australian National Health and Medical Research Council from December 2014. METHODS/DESIGN: An integrated mixed methods approach will be adopted; each component iteratively informing the other. Using an interrupted time series design, the primary research methods are quantitative: 1) assessment of change in students' resilience, educational outcomes and suicide risk; and 2) calculation of costs of the intervention. Secondary methods are qualitative: 3) a grounded theoretical model of the process of enhancing students' psychosocial resilience to protect against suicide. Additionally, there is a tertiary focus on capacity development: more experienced researchers in the team will provide research mentorship to less experienced researchers through regular meetings; while Indigenous team members provide cultural mentorship in research practices to non-Indigenous members. DISCUSSION: Australia's suicide prevention policy is progressive but a strong service delivery model is lacking, particularly for Indigenous peoples. The proposed research will potentially improve students' levels of resilience to mitigate against suicide risk. Additionally, it could reduce the economic and social costs of Indigenous youth suicide by obtaining agreement on what is good suicide prevention practice for remote Indigenous students who transition to boarding schools for education, and identifying the benefits-costs of an evidence-based multi-component mentoring intervention to improve resilience. PMID- 26833340 TI - The geospatial data quality REST API for primary biodiversity data. AB - We present a REST web service to assess the geospatial quality of primary biodiversity data. It enables access to basic and advanced functions to detect completeness and consistency issues as well as general errors in the provided record or set of records. The API uses JSON for data interchange and efficient parallelization techniques for fast assessments of large datasets. AVAILABILITY AND IMPLEMENTATION: The Geospatial Data Quality API is part of the VertNet set of APIs. It can be accessed at http://api-geospatial.vertnet portal.appspot.com/geospatial and is already implemented in the VertNet data portal for quality reporting. Source code is freely available under GPL license from http://www.github.com/vertnet/api-geospatial CONTACT: javier.otegui@gmail.com or rguralnick@flmnh.ufl.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26833341 TI - Integrative analysis for identifying joint modular patterns of gene-expression and drug-response data. AB - MOTIVATION: The underlying relationship between genomic factors and the response of diverse cancer drugs still remains unclear. A number of studies showed that the heterogeneous responses to anticancer treatments of patients were partly associated with their specific changes in gene expression and somatic alterations. The emerging large-scale pharmacogenomic data provide us valuable opportunities to improve existing therapies or to guide early-phase clinical trials of compounds under development. However, how to identify the underlying combinatorial patterns among pharmacogenomics data are still a challenging issue. RESULTS: In this study, we adopted a sparse network-regularized partial least square (SNPLS) method to identify joint modular patterns using large-scale pairwise gene-expression and drug-response data. We incorporated a molecular network to the (sparse) partial least square model to improve the module accuracy via a network-based penalty. We first demonstrated the effectiveness of SNPLS using a set of simulation data and compared it with two typical methods. Further, we applied it to gene expression profiles for 13 321 genes and pharmacological profiles for 98 anticancer drugs across 641 cancer cell lines consisting of diverse types of human cancers. We identified 20 gene-drug co-modules, each of which consists of 30 cell lines, 137 genes and 2 drugs on average. The majority of identified co-modules have significantly functional implications and coordinated gene-drug associations. The modular analysis here provided us new insights into the molecular mechanisms of how drugs act and suggested new drug targets for therapy of certain types of cancers. AVAILABILITY AND IMPLEMENTATION: A matlab package of SNPLS is available at http://page.amss.ac.cn/shihua.zhang/ CONTACT: : zsh@amss.ac.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26833342 TI - Sprites: detection of deletions from sequencing data by re-aligning split reads. AB - MOTIVATION: Advances of next generation sequencing technologies and availability of short read data enable the detection of structural variations (SVs). Deletions, an important type of SVs, have been suggested in association with genetic diseases. There are three types of deletions: blunt deletions, deletions with microhomologies and deletions with microsinsertions. The last two types are very common in the human genome, but they pose difficulty for the detection. Furthermore, finding deletions from sequencing data remains challenging. It is highly appealing to develop sensitive and accurate methods to detect deletions from sequencing data, especially deletions with microhomology and deletions with microinsertion. RESULTS: We present a novel method called Sprites (SPlit Read re alIgnment To dEtect Structural variants) which finds deletions from sequencing data. It aligns a whole soft-clipping read rather than its clipped part to the target sequence, a segment of the reference which is determined by spanning reads, in order to find the longest prefix or suffix of the read that has a match in the target sequence. This alignment aims to solve the problem of deletions with microhomologies and deletions with microinsertions. Using both simulated and real data we show that Sprites performs better on detecting deletions compared with other current methods in terms of F-score. AVAILABILITY AND IMPLEMENTATION: Sprites is open source software and freely available at https://github.com/zhangzhen/sprites CONTACT: jxwang@mail.csu.edu.cnSupplementary data: Supplementary data are available at Bioinformatics online. PMID- 26833343 TI - Model-based media selection to minimize the cost of metabolic cooperation in microbial ecosystems. AB - MOTIVATION: Simple forms of mutualism between microorganisms are widespread in nature. Nevertheless, the role played by the environmental nutrient composition in mediating cross-feeding in microbial ecosystems is still poorly understood. RESULTS: Here, we use mixed-integer bilevel linear programming to investigate the cost of sharing metabolic resources in microbial communities. The algorithm infers an optimal combination of nutrients that can selectively sustain synergistic growth for a pair of species and guarantees minimum cost of cross-fed metabolites. To test model-based predictions, we selected a pair of Escherichia coli single gene knockouts auxotrophic, respectively, for arginine and leucine: DeltaargB and DeltaleuB and we experimentally verified that model-predicted medium composition significantly favors mutualism. Moreover, mass spectrometry profiling of exchanged metabolites confirmed the predicted cross-fed metabolites, supporting our constraint based modeling approach as a promising tool for engineering microbial consortia. AVAILABILITY AND IMPLEMENTATION: The software is freely available as a matlab script in the Supplementary materials. CONTACT: zampieri@imsb.biol.ethz.ch SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26833344 TI - A zero-inflated Poisson model for insertion tolerance analysis of genes based on Tn-seq data. AB - MOTIVATION: Transposon insertion sequencing (Tn-seq) is an emerging technology that combines transposon mutagenesis with next-generation sequencing technologies for the identification of genes related to bacterial survival. The resulting data from Tn-seq experiments consist of sequence reads mapped to millions of potential transposon insertion sites and a large portion of insertion sites have zero mapped reads. Novel statistical method for Tn-seq data analysis is needed to infer functions of genes on bacterial growth. RESULTS: In this article, we propose a zero-inflated Poisson model for analyzing the Tn-seq data that are high dimensional and with an excess of zeros. Maximum likelihood estimates of model parameters are obtained using an expectation-maximization (EM) algorithm, and pseudogenes are utilized to construct appropriate statistical tests for the transposon insertion tolerance of normal genes of interest. We propose a multiple testing procedure that categorizes genes into each of the three states, hypo tolerant, tolerant and hyper-tolerant, while controlling the false discovery rate. We evaluate the proposed method with simulation studies and apply the proposed method to a real Tn-seq data from an experiment that studied the bacterial pathogen, Campylobacter jejuniAvailability and implementation: We provide R code for implementing our proposed method at http://github.com/ffliu/TnSeq A user's guide with example data analysis is also available there. CONTACT: pliu@iastate.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26833345 TI - GiANT: gene set uncertainty in enrichment analysis. AB - Over the past years growing knowledge about biological processes and pathways revealed complex interaction networks involving many genes. In order to understand these networks, analysis of differential expression has continuously moved from single genes towards the study of gene sets. Various approaches for the assessment of gene sets have been developed in the context of gene set analysis (GSA). These approaches are bridging the gap between raw measurements and semantically meaningful terms.We present a novel approach for assessing uncertainty in the definition of gene sets. This is an essential step when new gene sets are constructed from domain knowledge or given gene sets are suspected to be affected by uncertainty. Quantification of uncertainty is implemented in the R-package GiANT. We also included widely used GSA methods, embedded in a generic framework that can readily be extended by custom methods. The package provides an easy to use front end and allows for fast parallelization. AVAILABILITY AND IMPLEMENTATION: The package GiANT is available on CRAN. CONTACTS: hans.kestler@leibniz-fli.de or hans.kestler@uni-ulm.de. PMID- 26833346 TI - Optimization of alignment-based methods for taxonomic binning of metagenomics reads. AB - MOTIVATION: Alignment-based taxonomic binning for metagenome characterization proceeds in two steps: reads mapping against a reference database (RDB) and taxonomic assignment according to the best hits. Beyond the sequencing technology and the completeness of the RDB, selecting the optimal configuration of the workflow, in particular the mapper parameters and the best hit selection threshold, to get the highest binning performance remains quite empirical. RESULTS: We developed a statistical framework to perform such optimization at a minimal computational cost. Using an optimization experimental design and simulated datasets for three sequencing technologies, we built accurate prediction models for five performance indicators and then derived the parameter configuration providing the optimal performance. Whatever the mapper and the dataset, we observed that the optimal configuration yielded better performance than the default configuration and that the best hit selection threshold had a large impact on performance. Finally, on a reference dataset from the Human Microbiome Project, we confirmed that the optimized configuration increased the performance compared with the default configuration. AVAILABILITY AND IMPLEMENTATION: Not applicable. CONTACT: magali.dancette@biomerieux.com SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26833347 TI - Hepatitis C and not Hepatitis B virus is a risk factor for anti-tuberculosis drug induced liver injury. AB - BACKGROUND: The risk of anti-tuberculosis (TB) drug-induced liver injury (DILI) in patients with chronic viral hepatitis (CVH) is not clear. The aim of this study was to investigate incidence and risk factors associated with TB DILI in CVH and non-CVH patients. METHODS: Retrospectively, a total of 128 CVH patients who received anti-TB medication from January 2005 to February 2014 were reviewed. Among these, 83 patients had hepatitis B virus (HBV), 41 patients had hepatitis C virus (HCV) and 4 patients were dual hepatitis B and hepatitis C virus co infected (HBV + HCV) with 251 non-CVH patients who received anti-TB medication selected as the controls. There were no human immunodeficiency virus co-infected patients. Risk factors for DILI were analyzed using cox regression analysis. RESULTS: The incidence of DILI was significantly higher in the HCV group (13/41 [31.7%], p < 0.001) and HBV + HCV groups (3/4 [75.0%], p = 0.002) compared to the control group (25/251 [10.0%]). The incidence of transient liver function impairment in the hepatitis B virus group was higher than in the control group (18/83 [21.7%] vs. 27/251 [10.8%] p = 0.010), but not in DILI (11/83 [13.3%] vs. 25/251 [10.0%], p = 0.400). In total patients, HCV, HBV + HCV co-infection, older age, and baseline liver function abnormality were independent factors of DILI. CONCLUSIONS: It is recommended to carefully monitor for DILI in patients with HCV or HBV/HCV co-infection, older age, and baseline liver function abnormality. PMID- 26833348 TI - Effects of Age on Glycemic Control in Patients With Type 2 Diabetes Treated with Insulin Detemir: A Post-Hoc Analysis of the PREDICTIVETM 303 Study. AB - BACKGROUND: This post-hoc sub-analysis investigated whether age (<65 years vs >=65 years) affects glycemic control or hypoglycemic risk in patients with type 2 diabetes mellitus (T2DM) treated with once-daily insulin detemir. METHODS: This was a 26-week, randomized, open-label, phase IV trial involving 2812 patients at 1083 predominantly primary care sites throughout the United States, of which 541 were designated for investigator-led insulin titration. The main efficacy measure was change in HbA1c (A1C) from baseline to Week 26. Patients were stratified by age in the sites designated for the investigator-led titration of insulin detemir. Safety measures included adverse events and change in hypoglycemic event rates from baseline to Week 26. RESULTS: At Week 26, mean A1C and fasting plasma glucose decreased in both groups, but mean differences in change from baseline were not significant between groups. Within the group >=65 years, significant reductions occurred for all daytime hypoglycemia, but there was no significant change from baseline in the other categories. In the group <65 years, reductions from baseline were significant for all hypoglycemic event categories. Changes in hypoglycemia rates from baseline were not significantly different between the age groups and there was no weight increase in either age group. CONCLUSIONS: This analysis demonstrates that insulin detemir has similar efficacy and safety profiles for patients with T2DM >=65 years compared with <65 years when treated via an investigator-led algorithm. PMID- 26833349 TI - The Effect of Sleep Medication Use and Poor Sleep Quality on Risk of Falls in Community-Dwelling Older Adults in the US: A Prospective Cohort Study. AB - BACKGROUND: Sleep complaints and the consumption of medications for sleep are common in older adults. Falls are also a significant concern for older adults and sedative use has been identified as a risk factor for falls. Sleep quality is a potential confounder in studies evaluating the relationship between sleep medication use and falls. However, very few studies have assessed the combined impact of sleep medication use and sleep quality on the risk of falls. OBJECTIVE: The objective of this study was to evaluate the association between sleep medication use, poor sleep quality, and falls in community-dwelling older adults. METHODS: This was a multicenter, 6-month prospective cohort study conducted in senior housings settings in central Virginia, USA. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and a medication review was conducted. Data regarding falls were collected over 6 months by use of a diary. Logistic regression modeling was used to examine the effects of poor sleep quality, sleep medication use, and both, on the risk of falls. RESULTS: Among 113 independently living older adults (mean age +/- standard deviation 81.1 +/- 8.6), 46.9 % fell at least once during a 6-month period; 62.8 % (n = 71) had poor sleep quality, and 44.2 % (n = 50) used medications or treatments to aid sleep. Compared with participants reporting good sleep quality and no sleep medication use, those who reported poor sleep quality and sleep medication use had an increased risk of falls after adjusting for covariates (odds ratio 3.23, 95 % confidence interval 1.05-9.91). The group with good sleep quality and sleep medication use, as well as the group with poor sleep quality and no sleep medication use had no significantly greater risk for falls compared with the group with good sleep quality and no sleep medication use. CONCLUSION: A combined effect of sleep quality and sleep medication use on the risk of falls suggests that medication effectiveness may be an important factor to consider in understanding the risk of falls associated with sedative medications. PMID- 26833350 TI - Targeting Low Disease Activity in Elderly-Onset Rheumatoid Arthritis: Current and Future Roles of Biological Disease-Modifying Antirheumatic Drugs. AB - Elderly rheumatoid arthritis (RA) is classified into two clinical subsets, elderly-onset RA (EORA) and younger-onset elderly RA. With the improvement of life expectancy in the general population and advent of the super-aging society, the number of patients with EORA is anticipated to increase. Both large and small joints are affected initially at onset, and individuals with early EORA have higher scores of disease activity and levels of acute-phase reactants than those with early younger-onset RA. EORA is a progressive disease similar to younger onset RA. Tumor necrosis factor (TNF) inhibitors are equally or slightly less effective in elderly patients than in younger patients with RA, and disease duration may have a greater impact on disease outcomes than age. Evidence of non TNF biological disease-modifying antirheumatic drug use in EORA is limited. TNF inhibitors may not increase the risk for infection in elderly patients any more than methotrexate; however, increasing age is an independent and strong risk factor for serious infections in patients with RA. Treatment choice in patients with EORA is strongly influenced by comorbidities, especially cardiovascular disease, chronic lung disease, and frailty. To prevent progression to irreversible geriatric syndromes, non-frail patients with EORA, who are aging successfully should undergo intensive treatment using the treat-to-target strategy, and pre-frail and frail patients with EORA should be treated with the aim of returning to a non-frail or pre-frail stage, respectively. An appropriate treatment strategy for EORA and younger-onset elderly RA should be developed in the next decade using a multi-disciplinary approach. PMID- 26833352 TI - A New Method for Individualized Digoxin Dosing in Elderly Patients. AB - BACKGROUND: Digoxin is a frequently prescribed drug in the elderly population. Estimated glomerular filtration rate is widely used to adjust dosages. The HUGE value is a tool for differentiating the presence or absence of chronic kidney disease in elderly patients. We aimed to investigate the usefulness of the HUGE value to predict the initial dose of digoxin in patients aged older than 70 years. METHODS: We reviewed retrospectively the medical records of patients aged older than 70 years with serum digoxin concentrations (SDCs) monitored over a 6 month period (63 patients). A linear regression relating the patient's SDC, maintenance dose of digoxin and the HUGE value was estimated to generate a dosage equation. This equation was validated retrospectively (33 patients) and prospectively (35 patients) in comparison with two existing methods based on creatinine clearance. RESULTS: An equation (HUGE_DIG) was generated to calculate the initial digoxin dose to reach a specific target SDC. Thus, to achieve a SDC of 0.8 ng/mL: Digoxin (mg/day) = 0.091 - 0.006 x HUGE. After retrospective validation, the calculated digoxin doses with this equation were administered in the prospective phase and we did not observe statistical differences between measured and desired SDCs. Moreover, the predictive performance of our equation was better than that obtained with the compared methods. CONCLUSIONS: We offer a new validated digoxin dosing equation for elderly patients. Our results support the need to perform digoxin dosing in elderly people, bearing in mind the changes in renal physiology secondary to ageing and not merely the estimated glomerular filtration rate. PMID- 26833353 TI - Overexpression of Vitreoscilla hemoglobin increases waterlogging tolerance in Arabidopsis and maize. AB - BACKGROUND: Vitreoscilla hemoglobin (VHb) is a type of hemoglobin found in the Gram-negative aerobic bacterium Vitreoscilla that has been shown to contribute to the tolerance of anaerobic stress in multiple plant species. Maize (Zea mays L.) is susceptible to waterlogging, causing significant yield loss. In this study, we approached this problem with the introduction of an exogenous VHb gene. RESULTS: We overexpressed the VHb gene in Arabidopsis and maize under the control of the CaMV35S promoter. After 14 days of waterlogging treatment, the transgenic VHb Arabidopsis plants remained green, while the controls died. Under waterlogging, important plant growth traits of VHb plants, including seedling height, primary root length, lateral root number, and shoot dry weight were significantly improved relative to those of the controls. The VHb gene was also introduced into a maize line through particle bombardment and was then transferred to two elite maize inbred lines through marker-assisted backcrossing. The introduction of VHb significantly enhanced plant growth under waterlogging stress on traits, including seedling height, primary root length, lateral root number, root dry weight, and shoot dry weight, in both Zheng58 and CML50 maize backgrounds. Under the waterlogging condition, transgenic VHb maize seedlings exhibited elevated expression of alcohol dehydrogenase (ADH1) and higher peroxidase (POD) enzyme activity. The two VHb-containing lines, Zheng58 (VHb) and CML50 (VHb), exhibited higher tolerance to waterlogging than their negative control lines (Zheng58 and CML50). CONCLUSIONS: These results demonstrate that the exogenous VHb gene confers waterlogging tolerance to the transgenic maize line. In Maize in the place of to the transgenic maize line, the VHb gene is a useful molecular tool for the improvement of waterlogging and submergence-tolerance. PMID- 26833354 TI - Brief electrical stimulation after facial nerve transection and neurorrhaphy: a randomized prospective animal study. AB - BACKGROUND: Recent studies have examined the effects of brief electrical stimulation (BES) on nerve regeneration, with some suggesting that BES accelerates facial nerve recovery. However, the facial nerve outcome measurement in these studies has not been precise or accurate. The objective of this study is to assess the effect of BES on accelerating facial nerve functional recovery from a transection injury in the rat model. METHODS: A prospective randomized animal study using a rat model was performed. Two groups of 9 rats underwent facial nerve surgery. Both group 1 and 2 underwent facial nerve transection and repair at the main trunk of the nerve, with group 2 additionally receiving BES on post operative day 0 for 1 h using an implantable stimulation device. Primary outcome was measured using a laser curtain model, which measured amplitude of whisking at 2, 4, and 6 weeks post-operatively. RESULTS: At week 2, the average amplitude observed for group 1 was 4.4 degrees . Showing a statistically significant improvement over group 1, the group 2 mean was 14.0 degrees at 2 weeks post operatively (p = 0.0004). At week 4, group 1 showed improvement having an average of 9.7 degrees , while group 2 remained relatively unchanged with an average of 12.8 degrees . Group 1 had an average amplitude of 13.63 degrees at 6-weeks from surgery. Group 2 had a similar increase in amplitude with an average of 15.8 degrees . There was no statistically significant difference between the two groups at 4 and 6 weeks after facial nerve surgery. CONCLUSIONS: This is the first study to use an implantable stimulator for serial BES following neurorrhaphy in a validated animal model. Results suggest performing BES after facial nerve transection and neurorrhaphy at the main trunk of the facial nerve is associated with accelerated whisker movement in a rat model compared with a control group. PMID- 26833355 TI - Anisotropic Multishell Analytical Modeling of an Intervertebral Disk Subjected to Axial Compression. AB - Studies on intervertebral disk (IVD) response to various loads and postures are essential to understand disk's mechanical functions and to suggest preventive and corrective actions in the workplace. The experimental and finite-element (FE) approaches are well-suited for these studies, but validating their findings is difficult, partly due to the lack of alternative methods. Analytical modeling could allow methodological triangulation and help validation of FE models. This paper presents an analytical method based on thin-shell, beam-on-elastic foundation and composite materials theories to evaluate the stresses in the anulus fibrosus (AF) of an axisymmetric disk composed of multiple thin lamellae. Large deformations of the soft tissues are accounted for using an iterative method and the anisotropic material properties are derived from a published biaxial experiment. The results are compared to those obtained by FE modeling. The results demonstrate the capability of the analytical model to evaluate the stresses at any location of the simplified AF. It also demonstrates that anisotropy reduces stresses in the lamellae. This novel model is a preliminary step in developing valuable analytical models of IVDs, and represents a distinctive groundwork that is able to sustain future refinements. This paper suggests important features that may be included to improve model realism. PMID- 26833351 TI - Infection in Venous Leg Ulcers: Considerations for Optimal Management in the Elderly. AB - Venous leg ulcers are the most common cause of chronic leg wounds, accounting for up to 70 % of all chronic leg ulcers and carrying with them a significant morbidity, especially for elderly patients. Among people aged 65 years and older, the annual prevalence is 1.7 %. Billions of dollars per year are spent caring for patients with these often difficult-to-heal and sometimes recurrent chronic wounds. Chronic non-healing wounds of the lower extremities are susceptible to microbial invasion and can lead to serious complications, such as delayed healing, cellulitis, enlargement of wound size, debilitating pain, and deeper wound infections causing systemic illness. Recognition and treatment of the infected venous leg ulcer is an essential skill set for any physician caring for geriatric patients. Most physicians rely on subjective clinical signs and patient reported symptoms in the evaluation of infected chronic wounds. The conventional bacterial culture is a widely available tool for the diagnosis of bacterial infection but can have limitations. Systemic antibiotics, as well as topical antiseptics and antibiotics, can be employed to treat and control infection and critical colonization. Better understanding of microbial biofilms in the wound environment have caused them to emerge as an important reason for non-healing and infection due to their increased resistance to antimicrobial, immunological, and chemical attack. A sound understanding of the microbial-host environment and its complexities, as well as the pathophysiology of venous hypertension, must be appreciated to understand the need for a multimodality approach to treating an infected venous leg ulcer. Other treatment measures are often required, in addition to systemic and topical antibiotics, such as the application of wound bandages, compression therapy, and wound debridement, which can hasten clearance of the infection and help to promote healing. PMID- 26833357 TI - Don't Bring Me Down--Too Fast! PMID- 26833356 TI - Mito-priming as a method to engineer Bcl-2 addiction. AB - Most apoptotic stimuli require mitochondrial outer membrane permeabilization (MOMP) in order to execute cell death. As such, MOMP is subject to tight control by Bcl-2 family proteins. We have developed a powerful new technique to investigate Bcl-2-mediated regulation of MOMP. This method, called mito-priming, uses co-expression of pro- and anti-apoptotic Bcl-2 proteins to engineer Bcl-2 addiction. On addition of Bcl-2 targeting BH3 mimetics, mito-primed cells undergo apoptosis in a rapid and synchronous manner. Using this method we have comprehensively surveyed the efficacy of BH3 mimetic compounds, identifying potent and specific MCL-1 inhibitors. Furthermore, by combining different pro- and anti-apoptotic Bcl-2 pairings together with CRISPR/Cas9-based genome editing, we find that tBID and PUMA can preferentially kill in a BAK-dependent manner. In summary, mito-priming represents a facile and robust means to trigger mitochondrial apoptosis. PMID- 26833358 TI - Developmental status of preschool children receiving cART: a descriptive cohort study. AB - BACKGROUND: HIV is known to cause neurodevelopmental problems in infants and young children. The impact of HIV on the development of preschool-age children has been less well described. METHOD: The study was conducted at an urban paediatric HIV clinic in Johannesburg, South Africa. A sample of convenience was used. Sixty-eight medically stable children between the ages of 3 and 5 years were assessed with the Griffiths Scales of Mental Development. Children were excluded from the study if they had severe HIV encephalopathy, which made it impossible for them to participate in the items on the Griffiths Scales of Mental Development. RESULTS: The children had started combination antiretroviral treatment (cART) at a mean age of 8.1 months. The majority of the children were virologically suppressed and did not present with wasting or stunting. Severe overall developmental delay (z-scores < -2SD) was detected in 55.88% of children. Developmental facets related to speech, cognition and perception were the most severely affected. Personal-social development was the least affected with only 13.4% of the children demonstrating severe delay. CONCLUSION: Despite having early access to cART, children infected with HIV are still at risk for severe developmental delay across a number of facets. Very early initiation of cART may help alleviate this problem. All preschool children infected with HIV should have routine developmental screening. PMID- 26833359 TI - Electrochemical Energy Storage Application and Degradation Analysis of Carbon Coated Hierarchical NiCo2S4 Core-Shell Nanowire Arrays Grown Directly on Graphene/Nickel Foam. AB - We developed a new electrode comprising thin carbon layer coated hierarchical NiCo2S4 core-shell nanowire arrays (NiCo2S4@C CSNAs) on graphene/Ni foam (Ni@G) substrates. The electrode showed outstanding electrochemical characteristics including a high specific capacitance of 253 mAh g(-1) at 3 A g(-1), high rate capability of 163 mAh g(-1) at 50 A g(-1) (~64.4% of that at 3 A g(-1)), and long term cycling stability with a capacity retention of 93.9% after 5000 cycles. Comparative studies on the degradation of hierarchical NiCo2S4 CSNA electrodes with and without carbon coatings revealed that the morphology pulverization, structural separation at core/shell interface, and irretrievably chemical composition change of NiCo2S4 CSNAs electrode are major factors that deteriorate the electrochemical performance of the electrodes without carbon coating. The favorable roles of carbon coatings on hierarchical NiCo2S4 CSNAs were further clarified: (1) serving as a physical buffering layer that suppresses the structural breakdown; (2) retarding the chemical composition conversion of the NiCo2S4 CSNAs; and (3) providing extra path for charge transition in addition to the NiCo2S4 core nanowires. Understanding of the degradation mechanisms and the significance of the surface carbon coatings would provide useful guidelines for the design of new electrode materials for high-performance electrochemical devices. PMID- 26833362 TI - Mechanical quality assurance using light field for linear accelerators with camera calibration. AB - Mechanical Quality Assurance (QA) is important to assure spatially precise delivery of external-beam radiation therapy. As an alternative to the conventional-film based method, we have developed a new tool for mechanical QA of LINACs which uses a light field rather than radiation. When light passes through the collimator, a shadow is projected onto a piece of translucent paper and the resulting image is captured by a digital camera via a mirror. With this method, we evaluated the position of the LINAC isocenter and the accuracy of the gantry, collimator, and couch rotation. We also evaluated the accuracy of the digital readouts of the gantry, collimator, and couch rotation. In addition, the treatment couch position indicator was tested. We performed camera calibration as an essential pre-requisite for quantitative measurements of the position of isocenter, the linear motion of the couch, and the rotation angles of the gantry and collimator. Camera calibration reduced the measurement error to submillimeter based on uncertainty in pixel size of the image, while, without calibration, the measurement error of up to 2 mm could occur for an object with a length of 5 cm. PMID- 26833360 TI - Non-fusion procedure using PEEK rod systems for lumbar degenerative diseases: clinical experience with a 2-year follow-up. AB - BACKGROUND: Polyetheretherketone (PEEK) rod system is a novel pedicle-based dynamic stabilization system. This study evaluated clinical and radiographic outcomes of non-fusion surgery by PEEK rod systems for treatment of degenerative lumbar diseases with a 2-year follow-up. METHODS: From February 2012 to October 2012, 38 patients who underwent non-fusion surgery using PEEK rod systems were included in the study. Data on Oswestry Disability Index (ODI) score and Japanese Orthopaedics Association (JOA) score were collected and radiographs were obtained to evaluate disc height index (DHI) and range of motion (ROM) at each interval. RESULTS: Both JOA and ODI scores significantly improved postoperatively. DHI showed a slight increase immediately after the surgery but gradually dropped below preoperative levels. Mean ROM values changed from 8.8 degrees preoperatively to 1.8 degrees at the 2-year follow-up point. Screw loosening occurred in one case at the 2-year follow-up. CONCLUSIONS: The preliminary results indicated a significant improvement in clinical outcomes and advantageous implant safety. The non-fusion procedure using PEEK rod systems might be a viable alternative for treatment of lumbar degenerative diseases. The distraction technique needs to be improved for better postoperative DHI. PMID- 26833380 TI - Separation and quantification of lactate and lipid at 1.3 ppm by diffusion weighted magnetic resonance spectroscopy. AB - PURPOSE: To separate the spectrally overlapped lactate and lipid signals at 1.3 ppm using diffusion-weighted magnetic resonance spectroscopy (DW-MRS) based on their large diffusivity difference. METHODS: DW-MRS was applied to the gel phantoms containing lactate and lipid droplets, and to the rat brain tumors. Lactate and lipid signals and their apparent diffusion coefficients were computed from the diffusion-weighted proton spectra. Biexponential fitting and direct spectral subtraction approaches were employed and compared. RESULTS: DW-MRS could effectively separate lactate and lipid signals both in phantoms and rat brain C6 glioma by biexponential fitting. In phantoms, lactate and lipid signals highly correlated with the known lactate concentration and lipid volume fractions. In C6 glioma, both lactate and lipid signals were detected, and the lipid signal was an order of magnitude higher than lactate signal. The spectral subtraction approach using three diffusion weightings also allowed the separation of lactate and lipid signals, yielding results comparable to those by the biexponential fitting approach. CONCLUSION: DW-MRS presents a new approach to separate and quantify spectrally overlapped molecules and/or macromolecules, such as lactate and lipid, by using the diffusivity difference associated with their different sizes or mobility within tissue microstructure. Magn Reson Med 77:480-489, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26833381 TI - 4Pi-RESOLFT nanoscopy. AB - By enlarging the aperture along the optic axis, the coherent utilization of opposing objective lenses (4Pi arrangement) has the potential to offer the sharpest and most light-efficient point-spread-functions in three-dimensional (3D) far-field fluorescence nanoscopy. However, to obtain unambiguous images, the signal has to be discriminated against contributions from lobes above and below the focal plane, which has tentatively limited 4Pi arrangements to imaging samples with controllable optical conditions. Here we apply the 4Pi scheme to RESOLFT nanoscopy using two-photon absorption for the on-switching of fluorescent proteins. We show that in this combination, the lobes are so low that low-light level, 3D nanoscale imaging of living cells becomes possible. Our method thus offers robust access to densely packed, axially extended cellular regions that have been notoriously difficult to super-resolve. Our approach also entails a fluorescence read-out scheme that translates molecular sensitivity to local off switching rates into improved signal-to-noise ratio and resolution. PMID- 26833382 TI - Thoracic (99m)Tc-MAA accumulations due to aberrant arteries originating from the phrenic artery. PMID- 26833383 TI - Infected concha bullosa mimicking a malignant lesion on (18)F-FDG PET/CT. PMID- 26833384 TI - Dynamic metabolic changes in seeds and seedlings of Brassica napus (oilseed rape) suppressing UGT84A9 reveal plasticity and molecular regulation of the phenylpropanoid pathway. AB - In Brassica napus, suppression of the key biosynthetic enzyme UDP-glucose:sinapic acid glucosyltransferase (UGT84A9) inhibits the biosynthesis of sinapine (sinapoylcholine), the major phenolic component of seeds. Based on the accumulation kinetics of a total of 158 compounds (110 secondary and 48 primary metabolites), we investigated how suppression of the major sink pathway of sinapic acid impacts the metabolome of developing seeds and seedlings. In UGT84A9 suppressing (UGT84A9i) lines massive alterations became evident in late stages of seed development affecting the accumulation levels of 58 secondary and 7 primary metabolites. UGT84A9i seeds were characterized by decreased amounts of various hydroxycinnamic acid (HCA) esters, and increased formation of sinapic and syringic acid glycosides. This indicates glycosylation and beta-oxidation as metabolic detoxification strategies to bypass intracellular accumulation of sinapic acid. In addition, a net loss of sinapic acid upon UGT84A9 suppression may point to a feedback regulation of HCA biosynthesis. Surprisingly, suppression of UGT84A9 under control of the seed-specific NAPINC promoter was maintained in cotyledons during the first two weeks of seedling development and associated with a reduced and delayed transformation of sinapine into sinapoylmalate. The lack of sinapoylmalate did not interfere with plant fitness under UV-B stress. Increased UV-B radiation triggered the accumulation of quercetin conjugates whereas the sinapoylmalate level was not affected. PMID- 26833385 TI - The click-compatible sugar 6-deoxy-alkynyl glucose metabolically incorporates into Arabidopsis root hair tips and arrests their growth. AB - Plant cell walls are dynamic structures whose polysaccharide components are rearranged and recycled during growth and morphogenesis. Covalent fluorescent tagging of these polysaccharides following a metabolic labeling approach can help elucidate these changes. Herein reported are the synthesis and seedling incorporation of a plant polysaccharide chemical reporter, 6-deoxy-alkynyl glucose (6dAG), that is modeled on D-glucose. Whereas fucose-alkyne, a previously reported chemical reporter for pectin, incorporates diffusely throughout growing cell walls, 6dAG incorporated specifically into root hair tips. This incorporation occurs in a time- and concentration-dependent manner. 6dAG exposure both induces and colocalizes with callose deposition in this tissue, and arrests both root hair and root growth. These results show that plants can incorporate an additional alkynyl-modified sugar analog into their metabolism, and into a discrete subcellular location. PMID- 26833386 TI - Uncoupling Catalytic and Binding Functions in the Cyclic AMP-Dependent Protein Kinase A. AB - The canonical function of kinases is to transfer a phosphoryl group to substrates, initiating a signaling cascade; while their non-canonical role is to bind other kinases or substrates, acting as scaffolds, competitors, and signal integrators. Here, we show how to uncouple kinases' dual function by tuning the binding cooperativity between nucleotide (or inhibitors) and substrate allosterically. We demonstrate this new concept for the C subunit of protein kinase A (PKA-C). Using thermocalorimetry and nuclear magnetic resonance, we found a linear correlation between the degree of cooperativity and the population of the closed state of PKA-C. The non-hydrolyzable ATP analog (ATPgammaC) does not follow this correlation, suggesting that changing the chemical groups around the phosphoester bond can uncouple kinases' dual function. Remarkably, this uncoupling was also found for two ATP-competitive inhibitors, H89 and balanol. Since the mechanism for allosteric cooperativity is not conserved in different kinases, these results may suggest new approaches for designing selective kinase inhibitors. PMID- 26833389 TI - Tuning the Electronic Properties of Acetylenic Fluorenes by Phosphaalkene Incorporation. AB - Versatile synthetic protocols for 2,7- and 3,6-diacetylenic fluorene-9-ylidene phosphanes (F9Ps) were developed. Protodesilylation of trimethylsilyl-protected acetylenic F9Ps affords terminal acetylenes that can be employed in Sonogashira and Glaser-type C-C coupling reactions to give thienyl-decorated and butadiyne bridged fluorene-9-ylidene phosphanes, respectively. As evidenced by UV/Vis spectroscopy and cyclic voltammetry and corroborated by ab initio calculations, the presence of the P center in the F9Ps induces a significantly reduced HOMO LUMO splitting that originates from stabilization of the LUMO levels. Variation of the acetylene substitution pattern is an additional tool to influence the optical and electronic properties. Whereas 3,6-disubstituted F9Ps have strong absorptions around 400 nm, mainly due to pi-pi* transitions, 2,7-diacetylenic F9Ps exhibit longest-wavelength absorptions that have significant charge-transfer character with an onset around 520 nm. PMID- 26833387 TI - The Role of the Membrane in the Structure and Biophysical Robustness of the Dengue Virion Envelope. AB - The dengue virion is surrounded by an envelope of membrane proteins surrounding a lipid bilayer. We have combined the cryoelectron microscopy structures of the membrane proteins (PDB: 3J27) with a lipid bilayer whose composition is based on lipidomics data for insect cell membranes, to obtain a near-atomic resolution computational model of the envelope of the dengue virion. A coarse-grained molecular dynamics simulation on the microsecond timescale enables analysis of key biophysical properties of the dengue outer envelope. Properties analyzed include area per lipid values (for a spherical virion with a mixed lipid composition), bilayer thickness, and lipid diffusion coefficients. Despite the absence of cholesterol from the lipid bilayer, the virion exhibits biophysical robustness (slow lipid diffusion alongside stable bilayer thickness, virion diameter, and shape) that matches the cholesterol-rich membrane of influenza A, with similarly anomalous diffusion of lipids. Biophysical robustness of the envelope may confer resilience to environmental perturbations. PMID- 26833388 TI - Crystal Structure of a Soluble Fragment of the Membrane Fusion Protein HlyD in a Type I Secretion System of Gram-Negative Bacteria. AB - The protein toxin HlyA of Escherichia coli is exported without a periplasmic intermediate by the type I secretion system (T1SS). The T1SS is composed of an inner membrane ABC transporter HlyB, an outer-membrane channel protein TolC, and a membrane fusion protein HlyD. However, the assembly of the T1SS remains to be elucidated. In this study, we determine the crystal structure of a part of the C terminal periplasmic domain of HlyD. The long alpha-helical domain consisting of three alpha helices and a lipoyl domain was identified in the crystal structure. Based on the HlyD structure, we modeled the hexameric assembly of HlyD with a long alpha-helical barrel, which formed a complex with TolC in an intermeshing cogwheel-to-cogwheel manner, as observed in tripartite RND-type drug efflux pumps. These observations provide a structural blueprint for understanding the type I secretion system in pathogenic Gram-negative bacteria. PMID- 26833390 TI - The Effects of Frailty in Patients Undergoing Elective Cardiac Surgery. AB - BACKGROUND: The Society of Thoracic Surgeons (STS) recommends using gait speed as a marker of frailty to identify cardiac surgery patients at risk for adverse outcomes. However, a single marker of frailty may not provide consistently reliable risk information. We evaluated the impact of frailty and gait speed on patient outcomes after elective cardiac surgery. METHODS: This was a prospective study of 167 older (>=65 years) coronary artery bypass grafting (CABG) and/or valve surgery patients. Patients were assessed using Cardiovascular Health Study (CHS) Frailty Index criteria: weight loss, exhaustion, physical activity, gait speed, and grip strength. RESULTS: Frailty was identified in 39 patients (23%) using CHS criteria. Frail patients had longer median intensive care unit stays (54 vs. 28 h, p = 0.003), longer median length of stay (8 vs. 5 days, p < 0.001), and greater likelihood of STS-defined complications (54% vs. 32%, p = 0.011) and discharge to an intermediate-care facility (45% vs. 12%, p < 0.001) but were not different from nonfrail patients on major outcome, operative mortality, or readmissions. After multivariate adjustment, frail and nonfrail patients were similar on perioperative outcomes. Absolute gait speed and slow gait speed using a cutoff were not related to incidence of STS-defined complications or major outcome in multivariate analyses. However, higher body mass index was correlated with slower gait speed (rs = 0.30, p < 0.001). CONCLUSIONS: The CHS index did not identify "frail" patients at increased risk for adverse outcomes. No relationship was found between gait speed and outcome. There is a need for alternative multidimensional measures to assess frailty in cardiac surgical patients. doi: 10.1111/jocs.12699 (J Card Surg 2016;31:187-194). PMID- 26833391 TI - Effect of lemon verbena powder and vitamin C on performance and immunity of heat stressed broilers. AB - An experiment was conducted to investigate the effect of lemon verbena powder and vitamin C on performance and immunity of broilers under heat stress. The experiment was carried out with a total of 160-day-old male Ross 308 broiler chickens in a completely randomized design. From 25 days of age, the birds were assigned to four diets including control diet and treatment diets which were supplemented with 2 levels of lemon verbena (0.5% and 1.0%) and one level of vitamin C (250 mg/kg) in 16-floor pens with 10 chickens each and reared to 42 days of age. To induce chronic heat stress, birds were exposed to an ambient temperature of 35 +/- 2 degrees C for 8 h daily (from 09:00 AM until 17:00 PM) between 25 and 42 days of age. At the end of experiment, one chick/pen was randomly selected, and the performance and blood parameters were evaluated. Dietary supplementation of 1.0% lemon verbena increased (p < 0.05) average weight gain and feed intake by 5.81% and 3.29%, and reduced feed conversion ratio by 2.59% respectively compared to control group. Birds fed diets containing 1.0% lemon verbena had significantly higher relative weight of bursa of fabricius and breast (p < 0.05). LDL decreased by 15.85% and 17.57%, for birds fed 0.5% and 1.0% lemon verbena respectively. The ratio of heterophyl to lymphocyte was reduced (p < 0.05) by 20.68% via significant decrease in heterophyl by 15.55% and significant increase in lymphocyte by 4.51% in birds fed lemon verbena at the rate of 1.0% compared to those fed the control diet. 1.0% lemon verbena and vitamin C elevated (p = 0.0005) the level of glutathione peroxidase by 51.81% and 27.90%, respectively. In conclusion, lemon verbena and vitamin C improved some performance data and blood metabolites which somehow suppressed the negative effects of heat stress. PMID- 26833393 TI - A Supramolecular Chiral Auxiliary Approach: "Remote Control" of Stereochemistry at a Hierarchically Assembled Dimeric Helicate. AB - Dimeric hierarchically-assembled titanium(IV) helicates are in solvent-dependent equilibrium with the corresponding monomers. Statistically formed mixtures of such complexes bearing chiral stereocontrolling ligands and achiral diene substituted ligands show high diastereoselectivity and reasonable enantioselectivity in the Diels-Alder reaction with maleimides if the reaction proceeds with the dimer but not with the monomer. Thus, solvent dependent switching between the monomer and dimer enables on/off switching of the enantioselectivity. PMID- 26833392 TI - miR-150 regulates obesity-associated insulin resistance by controlling B cell functions. AB - Adipose tissue resident B cells account for more than 20% of stromal cells within visceral adipose tissues; however, their functions in the adipose tissue niche are poorly elucidated. Here we report that miR-150 modulates adipose tissue function by controlling activation of B cells and their interactions with other immune cells. miR-150KO mice displayed exacerbated obesity-associated tissue inflammation and systemic insulin resistance, which is recapitulated by adoptive transfer of B cells, but not purified immunoglobulin, into obese B(null) mice. Using purified cell populations, we found that enhanced proinflammatory activation of adipose tissue T cells and macrophages was due to miR-150KO B cells action but not cell-autologous mechanisms. miR-150KO B cells displayed significantly enhanced antigen presentation upon stimulation, ultimately leading to elevated inflammation and insulin resistance, compared to wild type B cells. Knockdown of identified miR-150 target genes, Elk1, Etf1 or Myb attenuated B cell action by altering B cell receptor pathways and MHCII cell surface presentation. Our results demonstrate a critical role for miR-150 in regulating B cell functions in adipose tissue which ultimately regulate both metabolic and immunologic homeostasis in the adipose tissue niche. PMID- 26833394 TI - Paediatric Behcet's disease: a UK tertiary centre experience. AB - There are currently limited data regarding paediatric Behcet's disease (BD), particularly in the UK. We describe the clinical spectrum, treatment and outcome of BD, and explore the relative sensitivities of the criteria for the diagnosis of BD in a UK paediatric cohort. Single retrospective case note review of children with a clinical diagnosis of BD presenting between 1987 and 2012. Demographics, clinical features, treatment and outcomes were recorded. The sensitivities of the International Study Group (ISG) and International Criteria for BD (ICBD) criteria were explored. BD disease activity was calculated using the Behcet's Disease Activity Index (BDAI). Forty-six patients (22 male) were identified. Median age of onset was 4.87 (0.04-15.71) years; median time to diagnosis was 3.74 (0.25-13.48) years. Clinical features were recurrent oral ulceration (97.8 %), recurrent genital ulceration (73.9 %), gastrointestinal (58.7 %), musculoskeletal (47.83 %), cutaneous (23.9 %) involvement and uveitis (2 %). Recurrent genital ulceration was more common in female patients (P = 0.044). Thirty-seven patients (80.4 %) fulfilled the ICBD criteria; only 12 patients (26.1 %) fulfilled the ISG criteria. BDAI score at diagnosis was 7/20 (0 10/20) and significantly decreased to 5/20 (0-9/20) (P < 0.0001) at latest follow up. The commonest systemic treatment was colchicine (76.1 %); anti-TNFalpha treatment was reserved for severe cases (15.5 %). Paediatric BD in the UK may present very early in life, sometimes with a family history, and with a low incidence of ocular involvement. Diagnostic delay is common. The majority of our patients required systemic therapy; anti-TNFalpha was reserved for severe cases and has largely superseded the use of thalidomide. PMID- 26833395 TI - Prevalence of rheumatic regional pain syndromes in Latin-American indigenous groups: a census study based on COPCORD methodology and syndrome-specific diagnostic criteria. AB - This study assessed the overall and specific prevalence of the main rheumatic regional pain syndromes (RRPS) in four Latin-American indigenous groups. A Community Oriented Program for Control of Rheumatic Diseases (COPCORD) methodology-based census study was performed in 4240 adults (participation rate: 78.88 %) in four indigenous groups: Chontal (Oaxaca, Mexico, n = 124), Mixteco (Oaxaca, Mexico; n = 937), Maya-Yucateco (Yucatan, Mexico; n = 1523), and Qom (Rosario, Argentina; n = 1656). Subjects with musculoskeletal pain were identified using a cross-cultural, validated COPCORD questionnaire administered by bilingual personnel, and reviewed by general practitioners or rheumatologists using standardized case definitions for the 12 most frequent RRPS. The overall prevalence of RRPS was confirmed in 239 cases (5.64 %, 95 % CI: 4.98-6.37). The prevalence in each group was Chontal n = 19 (15.32 %, 95 % CI: 10.03-22.69); Maya Yucateco n = 165 (10.83 %, 95 % CI: 9.37-12.49); Qom n = 48 (2.90 %, 95 % CI: 2.19-3.82); and Mixteco n = 7 (0.75 %, 95 % CI: 0.36-1.53). In the whole sample, the syndrome-specific prevalence was rotator cuff tendinopathy: 1.98 % (95 % CI: 1.60-2.45); lateral epicondylalgia: 0.83 % (95 % CI: 0.59-1.15); medial epicondylalgia: 0.73 % (95 % CI: 0.52-1.04); biceps tendinopathy: 0.71 % (95 % CI: 0.50-1.01); anserine syndrome: 0.64 % (95 % CI: 0.44-0.92); inferior heel pain: 0.61 % (95 % CI: 0.42-0.90); trochanteric syndrome: 0.49 % (95 % CI: 0.25 0.64); de Quervain's tendinopathy: 0.45 % (95 % CI: 0.29-0.70); trigger finger: 0.42 % (95 % CI: 0.27-0.67); carpal tunnel syndrome: 0.28 % (95 % CI: 0.16-0.49); Achilles tendinopathy (insertional): 0.12 % (95 % CI: 0.05-0.28); and Achilles tendinopathy (non-insertional): 0.07 % (95 % CI: 0.02-0.21). Leaving aside the comparison between Maya-Yucateco and Chontal groups (p = 0.18), we found significant differences (p < 0.001) in overall RRPS prevalence between the remaining pairs of indigenous groups. Syndrome-specific prevalences were also different between groups. Our findings support the hypothesis that overall RRPS prevalence and syndrome-specific prevalences are modulated by population-specific factors. PMID- 26833396 TI - Single-session gamified virtual reality exposure therapy for spider phobia vs. traditional exposure therapy: study protocol for a randomized controlled non inferiority trial. AB - BACKGROUND: Traditional one-session exposure therapy (OST) in which a patient is gradually exposed to feared stimuli for up to 3 h in a one-session format has been found effective for the treatment of specific phobias. However, many individuals with specific phobia are reluctant to seek help, and access to care is lacking due to logistic challenges of accessing, collecting, storing, and/or maintaining stimuli. Virtual reality (VR) exposure therapy may improve upon existing techniques by facilitating access, decreasing cost, and increasing acceptability and effectiveness. The aim of this study is to compare traditional OST with in vivo spiders and a human therapist with a newly developed single session gamified VR exposure therapy application with modern VR hardware, virtual spiders, and a virtual therapist. METHODS/DESIGN: Participants with specific phobia to spiders (N = 100) will be recruited from the general public, screened, and randomized to either VR exposure therapy (n = 50) or traditional OST (n = 50). A behavioral approach test using in vivo spiders will serve as the primary outcome measure. Secondary outcome measures will include spider phobia questionnaires and self-reported anxiety, depression, and quality of life. Outcomes will be assessed using a non-inferiority design at baseline and at 1, 12, and 52 weeks after treatment. DISCUSSION: VR exposure therapy has previously been evaluated as a treatment for specific phobias, but there has been a lack of high-quality randomized controlled trials. A new generation of modern, consumer ready VR devices is being released that are advancing existing technology and have the potential to improve clinical availability and treatment effectiveness. The VR medium is also particularly suitable for taking advantage of recent phobia treatment research emphasizing engagement and new learning, as opposed to physiological habituation. This study compares a market-ready, gamified VR spider phobia exposure application, delivered using consumer VR hardware, with the current gold standard treatment. Implications are discussed. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02533310. Registered on 25 August 2015. PMID- 26833398 TI - Preparation and investigation of nano-thick FTO/Ag/FTO multilayer transparent electrodes with high figure of merit. AB - In order to improve the conductivity of the single-layered nano-thick F doped SnO2 (FTO) thin films, an Ag mid-layer is embedded between the FTO layers. In our work, the effects of mid-layer Ag and top FTO layer on the structural, electrical and optical properties of FTO/Ag/FTO multilayered composite structures deposited on quartz glass substrates by magnetron sputtering at 100 degrees C have been investigated. As the thickness of Ag mid-layer increases, the resistivity decreases. As the top FTO layer thickness increases, the resistivity increases. The highest value of figure of merit phiTC is 7.8 * 10(-2 ) Omega(-1) for the FTO (20 nm)/Ag (7 nm)/FTO (30 nm) multilayers, while the average optical transmittance is 95.5% in the visible range of wavelengths and the resistivity is 8.8 * 10(-5 ) Omega.cm. In addition, we also describe the influence of Ag and top FTO layer thickness on structural, electrical and optical properties of the nano thick FTO (20 nm)/Ag/FTO multilayers and the mechanism of the changes of electrical and optical properties at different Ag and top FTO layer thicknesses. PMID- 26833397 TI - Efficacy and safety of Myofascial-meridian Release Acupuncture (MMRA) for chronic neck pain: a study protocol for randomized, patient- and assessor-blinded, sham controlled trial. AB - BACKGROUND: The purpose of this study is to evaluate the efficacy and safety of myofascial-meridian release acupuncture (MMRA) in the treatment of chronic neck pain compared with sham acupuncture. METHODS/DESIGN: A protocol for a randomized, patient- and assessor-blinded, sham controlled parallel trial is presented. Seventy-four participants with a >=3 month history of neck pain and a score of >=4 on the 11-point pain intensity numerical rating scale (PI-NRS) will be randomly assigned to the MMRA group (n = 37) or sham acupuncture group (n = 37). The participants will receive the MMRA treatment or sham acupuncture treatment twice per week for 4 weeks. The primary outcome is the mean change in the PI-NRS (0 = no pain and 10 = worst possible pain, 11-point Likert scale) from baseline to 4 weeks. The secondary outcomes are the mean change from baseline on the clinical relevance of the pain (ratio of changes greater than 1.5 or with percentiles greater than 30 % and 50 % in the PI-NRS), function (Neck Disability Index and Cervical Range of Motion), autonomic and psychometric measurements (Heart Rate Variability and Perceived Stress Scale), quality of life (EuroQol), global assessment (Patient Global Impression of Change), semi-objective outcomes (pressure pain threshold, consumption of rescue medicine and days of restricted activity) and immunologic/stress biomarkers. Adverse events will be evaluated at every visit. DISCUSSION: The results of this trial will provide evidence to confirm the efficacy and safety of acupuncture for chronic neck pain. TRIAL REGISTRATION: The trial is registered with the Clinical Research Information Service (CRiS), Republic of Korea: KCT0001573 . PMID- 26833399 TI - Macrophage activation syndrome: A severe and frequent manifestation of acute pancreatitis in 362 childhood-onset compared to 1830 adult-onset systemic lupus erythematosus patients. AB - OBJECTIVE: We previously reported a case series of acute pancreatitis (AP) and macrophage activation syndrome (MAS) in childhood (cSLE) patients; however, there are no data regarding the comparison of AP and MAS in large populations of cSLE and adult SLE (aSLE). METHODS: A study included 362 cSLE and 1830 aSLE patients. MAS was diagnosed according to preliminary diagnostic guidelines and AP according to the presence of abdominal pain or vomiting associated to an increase of pancreatic enzymes and/or pancreatic radiological abnormalities. Demographic data, clinical features, SLEDAI-2K, SLICC/ACR-DI, and treatment were assessed. RESULTS: Age in MAS patients was significantly lower compared with those without this complication [15 (8.8-55) vs. 33.5 (10.2-45.7) years, p = 0.007]. The frequencies of fever (94% vs. 37%, p = 0.001), leucopenia (82% vs. 19%, p = 0.0001), thrombocytopenia (65% vs. 19%, p = 0.013), hypertriglyceridemia (87% vs. 42%, p = 0.037), and hyperferritinemia (93% vs. 37%, p = 0.011) were also more frequently observed in AP patients with MAS compared in AP patients without MAS. Fever and hyperferritinemia concomitantly were more frequent in the former group (86% vs. 12%, p = 0.0015). Higher and significant frequency of AP in cSLE compared to aSLE patients [12/362 (3.3%) vs. 20/1830 (1.1%), p = 0.003], with similar AP duration [22 (6-60) vs. 15 (4-90) days, p = 0.534]. MAS (85% vs. 30%, p = 0.003) and death by MAS complication (31% vs. 0%, p = 0.017) were significantly higher in children compared with aSLE. CONCLUSIONS: This study provides novel data demonstrating that MAS occur in the majority of cSLE with AP with a higher mortality compared to aSLE. In addition, we identified in AP patients, a cluster of MAS clinical and laboratorial parameters more associated with this complication. PMID- 26833401 TI - Using smartphone-based applications (apps) in workplace health promotion: The opinion of German and Austrian leaders. AB - Reaching the actual target group for a web-based health promotion project turns out to be a difficult task. In this article, individual and organizational factors which can influence the decision of using apps in workplace health promotion are analyzed. Furthermore, we analyzed the opinion about feedback possibilities of apps in workplace health promotion. A study with 438 leaders was conducted, as leaders can be seen as a key factor in the success of health promotion projects. The results showed that younger leaders and leaders with a more positive attitude toward workplace health promotion are more likely to use an app. Furthermore, leaders with a positive attitude are more interested in expert-feedback than in instant feedback received from an app. PMID- 26833400 TI - Helicobacter pylori colonization in Nepal; assessment of prevalence and potential risk factors in a hospital-based patient cohort. AB - BACKGROUND: Helicobacter pylori, a gram-negative bacterium, can cause gastritis, peptic and duodenal ulcers. It is considered an important public health problem for both developed and developing world. This bacterium is classified as the class 1 carcinogen because it can cause cancer. METHODS: A hospital based study was conducted at Chitwan Medical College Teaching Hospital (CMCTH) from May to October 2014. Stool samples were collected from the suspected patients and were subjected to detection of the H. pylori stool antigen (HpSAg) following the procedures recommended by the manufacturer. A standard questionnaire on the potential risk factors was also designed and completed. RESULT: HpSAg was detected in 16 % of suspected patients. The children up to 10 years of age were found to be highly infected (36 %). The patients living in urban area were found more susceptible to develop H. pylori infection (P < 0.05). Tea drinking and repeated eating habit (more than twice a day) were listed as the important factors that can limit the H. pylori infections significantly (P < 0.05). CONCLUSION: In this hospital based study, a significant rate of prevalence was evaluated. However, we recommend a community based extensive study to reveal the real scenario of H. pylori infection in Nepalese populations. PMID- 26833402 TI - Modeling immune functions of the mouse blood-cerebrospinal fluid barrier in vitro: primary rather than immortalized mouse choroid plexus epithelial cells are suited to study immune cell migration across this brain barrier. AB - BACKGROUND: The blood-cerebrospinal fluid barrier (BCSFB) established by the choroid plexus (CP) epithelium has been recognized as a potential entry site of immune cells into the central nervous system during immunosurveillance and neuroinflammation. The location of the choroid plexus impedes in vivo analysis of immune cell trafficking across the BCSFB. Thus, research on cellular and molecular mechanisms of immune cell migration across the BCSFB is largely limited to in vitro models. In addition to forming contact-inhibited epithelial monolayers that express adhesion molecules, the optimal in vitro model must establish a tight permeability barrier as this influences immune cell diapedesis. METHODS: We compared cell line models of the mouse BCSFB derived from the Immortomouse((r)) and the ECPC4 line to primary mouse choroid plexus epithelial cell (pmCPEC) cultures for their ability to establish differentiated and tight in vitro models of the BCSFB. RESULTS: We found that inducible cell line models established from the Immortomouse((r)) or the ECPC4 tumor cell line did not express characteristic epithelial proteins such as cytokeratin and E-cadherin and failed to reproducibly establish contact-inhibited epithelial monolayers that formed a tight permeability barrier. In contrast, cultures of highly-purified pmCPECs expressed cytokeratin and displayed mature BCSFB characteristic junctional complexes as visualized by the junctional localization of E-cadherin, beta-catenin and claudins-1, -2, -3 and -11. pmCPECs formed a tight barrier with low permeability and high electrical resistance. When grown in inverted filter cultures, pmCPECs were suitable to study T cell migration from the basolateral to the apical side of the BCSFB, thus correctly modelling in vivo migration of immune cells from the blood to the CSF. CONCLUSIONS: Our study excludes inducible and tumor cell line mouse models as suitable to study immune functions of the BCSFB in vitro. Rather, we introduce here an in vitro inverted filter model of the primary mouse BCSFB suited to study the cellular and molecular mechanisms mediating immune cell migration across the BCSFB during immunosurveillance and neuroinflammation. PMID- 26833403 TI - Transcriptome analysis of Glomus mosseae/Medicago sativa mycorrhiza on atrazine stress. AB - Arbuscular mycorrhizal fungi (AMF) protect host plants against diverse biotic and abiotic stresses, and promote biodegradation of various contaminants. In this study effect of Glomus mosseae/Medicago sativa mycorrhiza on atrazine degradation was investigated. It was observed that the atrazine degradation rates with any addition level in mycorrhizal treatments were all significantly higher than those in non-mycorrhizal treatments. When atrazine was applied at 20 mg kg(-1), the removal efficiency was up to 74.65%. Therefore, G. mosseae can be considered as ideal inhabitants of technical installations to facilitate phytoremediation. Furthermore, a total of 10.4 Gb was used for de novo transcriptome assembly, resulting in a comprehensive data set for the identification of genes corresponding to atrazine stress in the AM association. After comparative analysis with edgeR, a total of 2,060 differential expressed genes were identified, including 570 up-regulated genes and 1490 down-regulated genes. After excluding 'function unknown' and 'general function predictions only' genes, 172 up-regulated genes were obtained. The differentially expressed genes in AM association with and without atrazine stress were associated with molecular processes/other proteins, zinc finger protein, intracellular/extracellular enzymes, structural proteins, anti-stress/anti-disease protein, electron transport-related protein, and plant growth associated protein. Our results not only prove AMF has important ecological significance on atrazine degradation but also provide evidence for the molecular mechanisms of atrazine degradation by AMF. PMID- 26833404 TI - Oral glutathione supplementation drastically reduces Helicobacter-induced gastric pathologies. AB - Helicobacter (H.) suis causes gastric pathologies in both pigs and humans. Very little is known on the metabolism of this bacterium and its impact on the host. In this study, we have revealed the importance of the glutamate-generating metabolism, as shown by a complete depletion of glutamine (Gln) in the medium during H. suis culture. Besides Gln, H. suis can also convert glutathione (GSH) to glutamate, and both reactions are catalyzed by the H. suis gamma glutamyltranspeptidase (GGT). Both for H. pylori and H. suis, it has been hypothesized that the degradation of Gln and GSH may lead to a deficiency for the host, possibly initiating or promoting several pathologies. Therefore the in vivo effect of oral supplementation with Gln and GSH was assessed. Oral supplementation with Gln was shown to temper H. suis induced gastritis and epithelial (hyper)proliferation in Mongolian gerbils. Astonishingly, supplementation of the feed with GSH, another GGT substrate, resulted in inflammation and epithelial proliferation levels returning to baseline levels of uninfected controls. This indicates that Gln and GSH supplementation may help reducing tissue damage caused by Helicobacter infection in both humans and pigs, highlighting their potential as a supportive therapy during and after Helicobacter eradication therapy. PMID- 26833405 TI - The modified corneocyte surface area measurement as an index of epidermal barrier properties: inverse correlation with transepidermal water loss. AB - BACKGROUND: Corneocyte surface area (CSA) is as established parameter for skin barrier function in humans. Measurement of canine CSA has been previously reported but has not been validated. HYPOTHESIS/OBJECTIVES: The aim of this study was to evaluate the validity of CSA as a barrier function parameter in dogs. ANIMALS: Six clinically normal beagle dogs. METHODS: CSA was measured and compared with transepidermal water loss (TEWL) using sequential tape stripping of the stratum corneum as a model of acute barrier disruption. Then, CSA and TEWL were measured at four anatomical sites (groin, lower back, nasal bridge and pinna). The correlation between the two indices was also evaluated. RESULTS: From the results of sequential tape stripping, CSA values gradually decreased with increasing number of tape strippings. The CSA values were inversely correlated with the TEWL ones. The two indices at different sites were variable and were strongly correlated. CONCLUSIONS AND CLINICAL IMPORTANCE: Canine CSA was demonstrated to be a useful parameter for the canine skin barrier function. The results from the anatomical sites imply that the cephalic sites (nasal bridge and pinna) were lower than others in skin barrier function. PMID- 26833406 TI - Exploiting drug repositioning and the brain microenvironment to treat brain metastases. PMID- 26833407 TI - L-Hydroxyproline and d-Proline Catabolism in Sinorhizobium meliloti. AB - Sinorhizobium meliloti forms N2-fixing root nodules on alfalfa, and as a free living bacterium, it can grow on a very broad range of substrates, including l proline and several related compounds, such as proline betaine, trans-4-hydroxy-l proline (trans-4-l-Hyp), and cis-4-hydroxy-d-proline (cis-4-d-Hyp). Fourteen hyp genes are induced upon growth of S. meliloti on trans-4-l-Hyp, and of those, hypMNPQ encodes an ABC-type trans-4-l-Hyp transporter and hypRE encodes an epimerase that converts trans-4-l-Hyp to cis-4-d-Hyp in the bacterial cytoplasm. Here, we present evidence that the HypO, HypD, and HypH proteins catalyze the remaining steps in which cis-4-d-Hyp is converted to alpha-ketoglutarate. The HypO protein functions as a d-amino acid dehydrogenase, converting cis-4-d-Hyp to Delta(1)-pyrroline-4-hydroxy-2-carboxylate, which is deaminated by HypD to alpha ketoglutarate semialdehyde and then converted to alpha-ketoglutarate by HypH. The crystal structure of HypD revealed it to be a member of the N-acetylneuraminate lyase subfamily of the (alpha/beta)8 protein family and is consistent with the known enzymatic mechanism for other members of the group. It was also shown that S. meliloti can catabolize d-proline as both a carbon and a nitrogen source, that d-proline can complement l-proline auxotrophy, and that the catabolism of d proline is dependent on the hyp cluster. Transport of d-proline involves the HypMNPQ transporter, following which d-proline is converted to Delta(1)-pyrroline 2-carboxylate (P2C) largely via HypO. The P2C is converted to l-proline through the NADPH-dependent reduction of P2C by the previously uncharacterized HypS protein. Thus, overall, we have now completed detailed genetic and/or biochemical characterization of 9 of the 14 hyp genes. IMPORTANCE: Hydroxyproline is abundant in proteins in animal and plant tissues and serves as a carbon and a nitrogen source for bacteria in diverse environments, including the rhizosphere, compost, and the mammalian gut. While the main biochemical features of bacterial hydroxyproline catabolism were elucidated in the 1960s, the genetic and molecular details have only recently been determined. Elucidating the genetics of hydroxyproline catabolism will aid in the annotation of these genes in other genomes and metagenomic libraries. This will facilitate an improved understanding of the importance of this pathway and may assist in determining the prevalence of hydroxyproline in a particular environment. PMID- 26833408 TI - Vibrio cholerae FeoA, FeoB, and FeoC Interact To Form a Complex. AB - Feo is the major ferrous iron transport system in prokaryotes. Despite having been discovered over 25 years ago and found to be widely distributed among bacteria, Feo is poorly understood, as its structure and mechanism of iron transport have not been determined. The feo operon in Vibrio cholerae is made up of three genes, encoding the FeoA, FeoB, and FeoC proteins, which are all required for Feo system function. FeoA and FeoC are both small cytoplasmic proteins, and their function remains unclear. FeoB, which is thought to function as a ferrous iron permease, is a large integral membrane protein made up of an N terminal GTPase domain and a C-terminal membrane-spanning region. To date, structural studies of FeoB have been carried out using a truncated form of the protein encompassing only the N-terminal GTPase region. In this report, we show that full-length FeoB forms higher-order complexes when cross-linked in vivo in V. cholerae. Our analysis of these complexes revealed that FeoB can simultaneously associate with both FeoA and FeoC to form a large complex, an observation that has not been reported previously. We demonstrate that interactions between FeoB and FeoA, but not between FeoB and FeoC, are required for complex formation. Additionally, we identify amino acid residues in the GTPase region of FeoB that are required for function of the Feo system and for complex formation. These observations suggest that this large Feo complex may be the active form of Feo that is used for ferrous iron transport. IMPORTANCE: The Feo system is the major route for ferrous iron transport in bacteria. In this work, the Vibrio cholerae Feo proteins, FeoA, FeoB, and FeoC, are shown to interact to form a large inner membrane complex in vivo. This is the first report showing an interaction among all three Feo proteins. It is also determined that FeoA, but not FeoC, is required for Feo complex assembly. PMID- 26833409 TI - Short-Stalked Prosthecomicrobium hirschii Cells Have a Caulobacter-Like Cell Cycle. AB - The dimorphic alphaproteobacterium Prosthecomicrobium hirschii has both short stalked and long-stalked morphotypes. Notably, these morphologies do not arise from transitions in a cell cycle. Instead, the maternal cell morphology is typically reproduced in daughter cells, which results in microcolonies of a single cell type. In this work, we further characterized the short-stalked cells and found that these cells have a Caulobacter-like life cycle in which cell division leads to the generation of two morphologically distinct daughter cells. Using a microfluidic device and total internal reflection fluorescence (TIRF) microscopy, we observed that motile short-stalked cells attach to a surface by means of a polar adhesin. Cells attached at their poles elongate and ultimately release motile daughter cells. Robust biofilm growth occurs in the microfluidic device, enabling the collection of synchronous motile cells and downstream analysis of cell growth and attachment. Analysis of a draft P. hirschii genome sequence indicates the presence of CtrA-dependent cell cycle regulation. This characterization of P. hirschii will enable future studies on the mechanisms underlying complex morphologies and polymorphic cell cycles. IMPORTANCE: Bacterial cell shape plays a critical role in regulating important behaviors, such as attachment to surfaces, motility, predation, and cellular differentiation; however, most studies on these behaviors focus on bacteria with relatively simple morphologies, such as rods and spheres. Notably, complex morphologies abound throughout the bacteria, with striking examples, such as P. hirschii, found within the stalked Alphaproteobacteria. P. hirschii is an outstanding candidate for studies of complex morphology generation and polymorphic cell cycles. Here, the cell cycle and genome of P. hirschii are characterized. This work sets the stage for future studies of the impact of complex cell shapes on bacterial behaviors. PMID- 26833410 TI - Arm-in-Arm Response Regulator Dimers Promote Intermolecular Signal Transduction. AB - Bacteriophytochrome photoreceptors (BphPs) and their cognate response regulators make up two-component signal transduction systems which direct bacteria to mount phenotypic responses to changes in environmental light quality. Most of these systems utilize single-domain response regulators to transduce signals through unknown pathways and mechanisms. Here we describe the photocycle and autophosphorylation kinetics of RtBphP1, a red light-regulated histidine kinase from the desert bacterium Ramlibacter tataouinensis RtBphP1 undergoes red to far red photoconversion with rapid thermal reversion to the dark state. RtBphP1 is autophosphorylated in the dark; this activity is inhibited under red light. The RtBphP1 cognate response regulator, the R. tataouinensis bacteriophytochrome response regulator (RtBRR), and a homolog, AtBRR from Agrobacterium tumefaciens, crystallize unexpectedly as arm-in-arm dimers, reliant on a conserved hydrophobic motif, hFWAhL (where h is a hydrophobic M, V, L, or I residue). RtBRR and AtBRR dimerize distinctly from four structurally characterized phytochrome response regulators found in photosynthetic organisms and from all other receiver domain homodimers in the Protein Data Bank. A unique cacodylate-zinc-histidine tag metal organic framework yielded single-wavelength anomalous diffraction phases and may be of general interest. Examination of the effect of the BRR stoichiometry on signal transduction showed that phosphorylated RtBRR is accumulated more efficiently than the engineered monomeric RtBRR (RtBRRmon) in phosphotransfer reactions. Thus, we conclude that arm-in-arm dimers are a relevant signaling intermediate in this class of two-component regulatory systems. IMPORTANCE: BphP histidine kinases and their cognate response regulators comprise widespread red light-sensing two-component systems. Much work on BphPs has focused on structural understanding of light sensing and on enhancing the natural infrared fluorescence of these proteins, rather than on signal transduction or the resultant phenotypes. To begin to address this knowledge gap, we solved the crystal structures of two single-domain response regulators encoded by a region immediately downstream of that encoding BphPs. We observed a previously unknown arm-in-arm dimer linkage. Monomerization via deletion of the C-terminal dimerization motif had an inhibitory effect on net response regulator phosphorylation, underlining the importance of these unusual dimers for signal transduction. PMID- 26833411 TI - The SOS Response Master Regulator LexA Regulates the Gene Transfer Agent of Rhodobacter capsulatus and Represses Transcription of the Signal Transduction Protein CckA. AB - The gene transfer agent of Rhodobacter capsulatus (RcGTA) is a genetic exchange element that combines central aspects of bacteriophage-mediated transduction and natural transformation. RcGTA particles resemble a small double-stranded DNA bacteriophage, package random ~4-kb fragments of the producing cell genome, and are released from a subpopulation (<1%) of cells in a stationary-phase culture. RcGTA particles deliver this DNA to surrounding R. capsulatus cells, and the DNA is integrated into the recipient genome though a process that requires homologs of natural transformation genes and RecA-mediated homologous recombination. Here, we report the identification of the LexA repressor, the master regulator of the SOS response in many bacteria, as a regulator of RcGTA activity. Deletion of the lexA gene resulted in the abolition of detectable RcGTA production and an ~10 fold reduction in recipient capability. A search for SOS box sequences in the R. capsulatus genome sequence identified a number of putative binding sites located 5' of typical SOS response coding sequences and also 5' of the RcGTA regulatory gene cckA, which encodes a hybrid histidine kinase homolog. Expression of cckA was increased >5-fold in the lexA mutant, and a lexA cckA double mutant was found to have the same phenotype as a DeltacckA single mutant in terms of RcGTA production. The data indicate that LexA is required for RcGTA production and maximal recipient capability and that the RcGTA-deficient phenotype of the lexA mutant is largely due to the overexpression of cckA. IMPORTANCE: This work describes an unusual phenotype of a lexA mutant of the alphaproteobacterium Rhodobacter capsulatus in respect to the phage transduction-like genetic exchange carried out by the R. capsulatus gene transfer agent (RcGTA). Instead of the expected SOS response characteristic of prophage induction, this lexA mutation not only abolishes the production of RcGTA particles but also impairs the ability of cells to receive RcGTA-borne genes. The data show that, despite an apparent evolutionary relationship to lambdoid phages, the regulation of RcGTA gene expression differs radically. PMID- 26833412 TI - Listeria monocytogenes sigmaH Contributes to Expression of Competence Genes and Intracellular Growth. AB - The alternative sigma factor sigma(H)has two functions in Gram-positive bacteria: it regulates sporulation and the development of genetic competence. Listeria monocytogenes is a nonsporulating species in which competence has not yet been detected. Nevertheless, the main competence regulators and a series of orthologous genes that form the competence machinery are present in its genome; some of the competence genes play a role in optimal phagosomal escape. In this study, strains overexpressing sigma(H) and strains with a sigma(H) deletion were used to elucidate the contribution of sigma(H) to the expression of the competence machinery genes inL. monocytogenes Gene expression analysis showed that sigma(H) is, indeed, involved in comG and come regulation. Unexpectedly, we observed a unique regulation scheme in which sigma(H) and the transcription factor ComK were involved. Population-level analysis showed that even with the overexpression of both factors, only a fraction of the cells expressed the competence machinery genes. Although we could not detect competence, sigma(H) was crucial for phagosomal escape, which implies that this alternative sigma factor has specifically evolved to regulate the L. monocytogenes intracellular life cycle. IMPORTANCE: Listeria monocytogenes can be an intracellular pathogen capable of causing serious infections in humans and animal species. Recently, the competence machinery genes were described as being necessary for optimal phagosomal escape, in which the transcription factor ComK plays an important role. On the other hand, our previous phylogenetic analysis suggested that the alternative sigma factor sigma(H) might play a role in the regulation of competence genes. The present study shows that some of the competence genes belong to the sigma(H) regulon and, importantly, that sigma(H) is essential for intracellular growth, implying a unique physiological role of sigma(H) among Firmicutes. PMID- 26833413 TI - Lanthanide-Dependent Regulation of Methanol Oxidation Systems in Methylobacterium extorquens AM1 and Their Contribution to Methanol Growth. AB - Methylobacterium extorquens AM1 has two distinct types of methanol dehydrogenase (MeDH) enzymes that catalyze the oxidation of methanol to formaldehyde. MxaFI MeDH requires pyrroloquinoline quinone (PQQ) and Ca in its active site, while XoxF-MeDH requires PQQ and lanthanides, such as Ce and La. Using MeDH mutant strains to conduct growth analysis and MeDH activity assays, we demonstrate that M. extorquens AM1 has at least one additional lanthanide-dependent methanol oxidation system contributing to methanol growth. Additionally, the abilities of different lanthanides to support growth were tested and strongly suggest that both XoxF and the unknown methanol oxidation system are able to use La, Ce, Pr, Nd, and, to some extent, Sm. Further, growth analysis using increasing La concentrations showed that maximum growth rate and yield were achieved at and above 1 MUM La, while concentrations as low as 2.5 nM allowed growth at a reduced rate. Contrary to published data, we show that addition of exogenous lanthanides results in differential expression from the xox1 and mxa promoters, upregulating genes in the xox1 operon and repressing genes in the mxa operon. Using transcriptional reporter fusions, intermediate expression from both the mxa and xox1 promoters was detected when 50 to 100 nM La was added to the growth medium, suggesting that a condition may exist under which M. extorquens AM1 is able to utilize both enzymes simultaneously. Together, these results suggest that M. extorquens AM1 actively senses and responds to lanthanide availability, preferentially utilizing the lanthanide-dependent MeDHs when possible. IMPORTANCE: The biological role of lanthanides is a nascent field of study with tremendous potential to impact many areas in biology. Our studies demonstrate that there is at least one additional lanthanide-dependent methanol oxidation system, distinct from the MxaFI and XoxF MeDHs, that may aid in classifying additional environmental organisms as methylotrophs. Further, our data suggest that M. extorquens AM1 has a mechanism to regulate which MeDH is transcribed, depending on the presence or absence of lanthanides. While the mechanism controlling differential regulation is not yet understood, further research into how methylotrophs obtain and use lanthanides will facilitate their cultivation in the laboratory and their use as a biomining and biorecycling strategy for recovery of these commercially valuable rare-earth elements. PMID- 26833414 TI - Sulfide Consumption in Sulfurimonas denitrificans and Heterologous Expression of Its Three Sulfide-Quinone Reductase Homologs. AB - Sulfurimonas denitrificans is a sulfur-oxidizing epsilonproteobacterium. It has been reported to grow with sulfide and to harbor genes that encode sulfide quinone reductases (SQRs) (catalyze sulfide oxidation). However, the actual sulfide concentrations at which S. denitrificans grows and whether its SQRs are functional remain enigmatic. Here, we illustrate the sulfide concentrations at which S. denitrificans exhibits good growth, namely, 0.18 mM to roughly 1.7 mM. Around 2.23 mM, sulfide appears to inhibit growth. S. denitrificans harbors three SQR homolog genes on its genome (Suden_2082 for type II SQR, Suden_1879 for type III SQR, and Suden_619 for type IV SQR). They are all transcribed in S. denitrificans. According to our experiments, they appear to be loosely bound to the membrane. Each individual S. denitrificans SQR was heterologously expressed in the Rhodobacter capsulatus SB1003 sqr deletion mutant, and all exhibited SQR activities individually. This suggests that all of these three genes encode functional SQRs. This study also provides the first experimental evidence of a functional bacterial type III SQR. IMPORTANCE: Although the epsilonproteobacterium Sulfurimonas denitrificans has been described as using many reduced sulfur compounds as electron donors, there is little knowledge about its growth with sulfide. In many bacteria, the sulfide-quinone reductase (SQR) is responsible for catalyzing sulfide oxidation. S. denitrificans has an array of different types of sqr genes on its genome and so do several other sulfur oxidizing Epsilonproteobacteria. However, whether these SQRs are functional has remained unknown. Here, we shed light on sulfide metabolism in S. denitrificans. Our study provides the first experimental evidence of active epsilonproteobacterial SQRs and also gives the first report of a functional bacterial type III SQR. PMID- 26833415 TI - The Composition of the Cell Envelope Affects Conjugation in Bacillus subtilis. AB - Conjugation in bacteria is the contact-dependent transfer of DNA from one cell to another via donor-encoded conjugation machinery. It is a major type of horizontal gene transfer between bacteria. Conjugation of the integrative and conjugative element ICEBs1 into Bacillus subtilis is affected by the composition of phospholipids in the cell membranes of the donor and recipient. We found that reduction (or elimination) of lysyl-phosphatidylglycerol caused by loss of mpr F caused a decrease in conjugation efficiency. Conversely, alterations that caused an increase in lysyl-phosphatidylglycerol, including loss of ugtP or overproduction of mprF, caused an increase in conjugation efficiency. In addition, we found that mutations that alter production of other phospholipids, e.g., loss of clsA and yfnI, also affected conjugation, apparently without substantively altering levels of lysyl-phosphatidylglycerol, indicating that there are multiple pathways by which changes to the cell envelope affect conjugation. We found that the contribution of mprF to conjugation was affected by the chemical environment. Wild-type cells were generally more responsive to addition of anions that enhanced conjugation, whereas mprF mutant cells were more sensitive to combinations of anions that inhibited conjugation at pH 7. Our results indicate that mprF and lysyl-phosphatidylglycerol allow cells to maintain relatively consistent conjugation efficiencies under a variety of ionic conditions. IMPORTANCE: Horizontal gene transfer is a driving force in microbial evolution, enabling cells that receive DNA to acquire new genes and phenotypes. Conjugation, the contact-dependent transfer of DNA from a donor to a recipient by a donor-encoded secretion machine, is a prevalent type of horizontal gene transfer. Although critically important, it is not well understood how the recipient influences the success of conjugation. We found that the composition of phospholipids in the membranes of donors and recipients influences the success of transfer of the integrative and conjugative element ICEBs1 in Bacillus subtilis Specifically, the presence of lysyl-phosphatidylglycerol enables relatively constant conjugation efficiencies in a range of diverse chemical environments. PMID- 26833416 TI - Rapid Evolution of Citrate Utilization by Escherichia coli by Direct Selection Requires citT and dctA. AB - The isolation of aerobic citrate-utilizing Escherichia coli (Cit(+)) in long-term evolution experiments (LTEE) has been termed a rare, innovative, presumptive speciation event. We hypothesized that direct selection would rapidly yield the same class of E. coli Cit(+) mutants and follow the same genetic trajectory: potentiation, actualization, and refinement. This hypothesis was tested with wild type E. coli strain B and with K-12 and three K-12 derivatives: an E. coli DeltarpoS::kan mutant (impaired for stationary-phase survival), an E. coli DeltacitT::kan mutant (deleted for the anaerobic citrate/succinate antiporter), and an E. coli DeltadctA::kan mutant (deleted for the aerobic succinate transporter). E. coli underwent adaptation to aerobic citrate metabolism that was readily and repeatedly achieved using minimal medium supplemented with citrate (M9C), M9C with 0.005% glycerol, or M9C with 0.0025% glucose. Forty-six independent E. coli Cit(+) mutants were isolated from all E. coli derivatives except the E. coli DeltacitT::kan mutant. Potentiation/actualization mutations occurred within as few as 12 generations, and refinement mutations occurred within 100 generations. Citrate utilization was confirmed using Simmons, Christensen, and LeMaster Richards citrate media and quantified by mass spectrometry. E. coli Cit(+) mutants grew in clumps and in long incompletely divided chains, a phenotype that was reversible in rich media. Genomic DNA sequencing of four E. coli Cit(+) mutants revealed the required sequence of mutational events leading to a refined Cit(+) mutant. These events showed amplified citT and dctA loci followed by DNA rearrangements consistent with promoter capture events for citT. These mutations were equivalent to the amplification and promoter capture CitT-activating mutations identified in the LTEE.IMPORTANCE E. coli cannot use citrate aerobically. Long-term evolution experiments (LTEE) performed by Blount et al. (Z. D. Blount, J. E. Barrick, C. J. Davidson, and R. E. Lenski, Nature 489:513-518, 2012, http://dx.doi.org/10.1038/nature11514 ) found a single aerobic, citrate-utilizing E. coli strain after 33,000 generations (15 years). This was interpreted as a speciation event. Here we show why it probably was not a speciation event. Using similar media, 46 independent citrate-utilizing mutants were isolated in as few as 12 to 100 generations. Genomic DNA sequencing revealed an amplification of the citT and dctA loci and DNA rearrangements to capture a promoter to express CitT, aerobically. These are members of the same class of mutations identified by the LTEE. We conclude that the rarity of the LTEE mutant was an artifact of the experimental conditions and not a unique evolutionary event. No new genetic information (novel gene function) evolved. PMID- 26833417 TI - Colanic Acid Intermediates Prevent De Novo Shape Recovery of Escherichia coli Spheroplasts, Calling into Question Biological Roles Previously Attributed to Colanic Acid. AB - After losing their protective peptidoglycan, bacterial spheroplasts can resynthesize a cell wall to recreate their normal shape. In Escherichia coli, this process requires the Rcs response. In its absence, spheroplasts do not revert to rod shapes but instead form enlarged spheroids and lyse. Here, we investigated the reason for this Rcs requirement. Rcs-deficient spheroids exhibited breaks and bulges in their periplasmic spaces and failed to synthesize a complete peptidoglycan cell wall, indicating that the bacterial envelope was defective. To determine the Rcs-dependent gene(s) required for shape recovery, we tested spheroplasts lacking selected RcsB-regulated genes and found that colanic acid (CA) biosynthesis appeared to be involved. Surprisingly, though, extracellular CA was not required for recovery. Instead, lysis was caused by mutations that interrupted CA biosynthesis downstream of the initial glycosyl transferase, WcaJ. Deleting wcaJ prevented lysis of spheroplasts lacking ensuing steps in the pathway, and providing WcaJ in trans to a mutant lacking the entire CA operon triggered spheroplast enlargement and lysis. Thus, CA is not required for spheroplast recovery. Instead, CA intermediates accumulate as dead-end products which inhibit recovery of wall-less cells. The results strongly imply that CA may not be required for the survival E. coli L-forms. More broadly, these findings mandate that previous conclusions about the role of colanic acid in biofilm formation or virulence must be reevaluated. IMPORTANCE: Wall-less bacteria can resynthesize their walls and recreate a normal shape, which in Escherichia coli requires the Rcs response. While attempting to identify the Rcs dependent gene required for shape recovery, we found that colanic acid (CA) biosynthesis appeared to be involved. Surprisingly, though, cell death was caused by mutations that interrupted CA biosynthesis downstream of the initial step in the pathway, creating dead-end compounds that inhibited recovery of wall-less cells. When testing for the biological role of CA, most previous experiments used mutants that would accumulate these deadly intermediates, meaning that all prior conclusions must be reexamined to determine if the results were caused by these lethal side effects instead of accurately reflecting the biological purpose of CA itself. PMID- 26833418 TI - Minicells, Back in Fashion. AB - Cryo-electron tomography (cryo-ET) has emerged as a leading technique for three dimensional visualization of large macromolecular complexes and their conformational changes in their native cellular environment. However, the resolution and potential applications of cryo-ET are fundamentally limited by specimen thickness, preventing high-resolution in situ visualization of macromolecular structures in many bacteria (such as Escherichia coli and Salmonella enterica). Minicells, which were discovered nearly 50 years ago, have recently been exploited as model systems to visualize molecular machines in situ, due to their smaller size and other unique properties. In this review, we discuss strategies for producing minicells and highlight their use in the study of chemotactic signaling, protein secretion, and DNA translocation. In combination with powerful genetic tools and advanced imaging techniques, minicells provide a springboard for in-depth structural studies of bacterial macromolecular complexes in situ and therefore offer a unique approach for gaining novel structural insights into many important processes in microbiology. PMID- 26833420 TI - Dimethyl sulphoxide modifies growth and senescence and induces the non-revertible petite phenotype in yeast. AB - Dimethyl sulphoxide is extensively used in chemical, pharmaceutical and biomedical applications, but its specific biological actions remain largely elusive. The aim of this study was to comprehensively explore the effects of dimethyl sulphoxide on eukaryotic growth and senescence by using the budding yeast Saccharomyces cerevisiae as a reliable model organism. Rather than focusing on single cells or on either the replicative or the chronological lifespan approach, well-established microbiological procedures were integrated to monitor a combination of physiological parameters. Cell proliferation, survival, reproductive competence and morphology were recorded at various time points during incubation of asynchronous yeast populations with increasing concentrations of dimethyl sulphoxide. The findings demonstrated a dose-dependent inhibitory effect of the compound on yeast proliferation, survival and reproduction. In parallel, dimethyl sulphoxide induced the acquisition of the non revertible petite phenotype and promoted morphological alterations that characterize senescence, driving the yeast populations towards the reproductive incompetent state. These findings point to the need for the investigation of the complex cellular and/or molecular mechanisms underlying the actions of dimethyl sulphoxide in eukaryotic cells and for the evaluation of their exploitation potential. PMID- 26833419 TI - Different Functions of Phylogenetically Distinct Bacterial Complex I Isozymes. AB - NADH:quinone oxidoreductase (complex I) is a bioenergetic enzyme that transfers electrons from NADH to quinone, conserving the energy of this reaction by contributing to the proton motive force. While the importance of NADH oxidation to mitochondrial aerobic respiration is well documented, the contribution of complex I to bacterial electron transport chains has been tested in only a few species. Here, we analyze the function of two phylogenetically distinct complex I isozymes in Rhodobacter sphaeroides, an alphaproteobacterium that contains well characterized electron transport chains. We found that R. sphaeroides complex I activity is important for aerobic respiration and required for anaerobic dimethyl sulfoxide (DMSO) respiration (in the absence of light), photoautotrophic growth, and photoheterotrophic growth (in the absence of an external electron acceptor). Our data also provide insight into the functions of the phylogenetically distinct R. sphaeroidescomplex I enzymes (complex IA and complex IE) in maintaining a cellular redox state during photoheterotrophic growth. We propose that the function of each isozyme during photoheterotrophic growth is either NADH synthesis (complex IA) or NADH oxidation (complex IE). The canonical alphaproteobacterial complex I isozyme (complex IA) was also shown to be important for routing electrons to nitrogenase-mediated H2 production, while the horizontally acquired enzyme (complex IE) was dispensable in this process. Unlike the singular role of complex I in mitochondria, we predict that the phylogenetically distinct complex I enzymes found across bacterial species have evolved to enhance the functions of their respective electron transport chains. IMPORTANCE: Cells use a proton motive force (PMF), NADH, and ATP to support numerous processes. In mitochondria, complex I uses NADH oxidation to generate a PMF, which can drive ATP synthesis. This study analyzed the function of complex I in bacteria, which contain more-diverse and more-flexible electron transport chains than mitochondria. We tested complex I function in Rhodobacter sphaeroides, a bacterium predicted to encode two phylogenetically distinct complex I isozymes. R. sphaeroides cells lacking both isozymes had growth defects during all tested modes of growth, illustrating the important function of this enzyme under diverse conditions. We conclude that the two isozymes are not functionally redundant and predict that phylogenetically distinct complex I enzymes have evolved to support the diverse lifestyles of bacteria. PMID- 26833421 TI - PUFA-induced cell death is mediated by Yca1p-dependent and -independent pathways, and is reduced by vitamin C in yeast. AB - Polyunsaturated fatty acids (PUFA) such as linoleic acid (LA, n-6, C18:2) and gamma-linolenic acid (GLA, n-6, C18:3) are essential and must be obtained from the diet. There has been a growing interest in establishing a bio-sustainable production of PUFA in several microorganisms, e.g. in yeast Saccharomyces cerevisiae. However, PUFAs can also be toxic to cells because of their susceptibility to peroxidation. Here we investigated the negative effects of LA and GLA production on S. cerevisiae by characterizing a strain expressing active Delta6 and Delta12 desaturases from the fungus Mucor rouxii. Previously, we showed that the PUFA-producing strain has low viability, down-regulated genes for oxidative stress response, and decreased proteasome activity. Here we show that the PUFA strain accumulates high levels of reactive oxygen species (ROS) and lipid peroxides, and accumulates damaged proteins. The PUFA strain also showed great increase in metacaspase Yca1p activity, suggesting cells could die by caspase-mediated cell death. When treated with antioxidant vitamin C, ROS, lipid peroxidation and protein carbonylation were greatly reduced, and the activity of the metacaspase was significantly decreased too, ultimately doubling the lifespan of the PUFA strain. When deleting YCA1, the caspase-like activity and the oxidative stress decreased and although the lifespan was slightly prolonged, the phenotype could not be fully reversed, pointing that Yca1p was not the main executor of cell death. PMID- 26833423 TI - Novel microspheres based on triterpene saponins from the roots of Physospermum verticillatum (Waldst & Kit) (Apiaceae) for the improvement of gemcitabine release. AB - OBJECTIVES: This study concerns the preparation and characterization of microspheres based on a mixture of triterpene saponins, from Physospermum verticillatum (Waldst & Kit), as a carrier for the specific release of gemcitabine. METHODS: Triterpene saponins were derivatized with acrylic acid. The obtained polymerizable product was characterized by Fourier transform infrared to confirm the ester linkage. Then, spherical microparticles were prepared by suspension radical copolymerization and impregnated with gemcitabine. KEY FINDINGS: Microspheres exhibited a mean diameter of 2.7 MU. The swelling studies showed that particles swell most at pH 6.2, typical of the tumour pathology, than at pH 7.4, miming physiological conditions. The microspheres were loaded with gemcitabine (LE 72.2%). Their release profile showed an initial dot of around 24% and a further release for 24 h. CONCLUSIONS: This carrier could be potentially release the drug in the lung, as a function of different pHs between tumour cells and healthy, reducing the systemic drug toxicity, allowing the reduction of the doses number, increasing the drug half-life and eliminating the problems related to the fast clearance of gemcitabine administration. PMID- 26833422 TI - ATRX in Diffuse Gliomas With its Mosaic/Heterogeneous Expression in a Subset. AB - This study aims (1) to evaluate ATRX expression in different grades and subtypes of gliomas and correlate with other hallmark genetic alterations, (2) to identify and characterize mosaic/heterogeneous staining in gliomas in terms of mutation status. One hundred seventy six cases of glioma were assessed for ATRX immunohistochemistry and subdivided into positive, negative and mosaic/heterogeneous staining patterns. Five cases with heterogeneous staining were further subjected to next generation sequencing. Higher frequency of ATRX immune-negativity was detected in grade II/III astrocytic, oligoastrocytic tumors and secondary glioblastomas (GBMs), while infrequent in primary GBMs and rare in oligodendrogliomas. Loss of expression was significantly associated with IDH1 and/or TP53 mutation, while mutually exclusive with 1p/19q codeletion. Mosaic/heterogeneous staining was detected exclusively in GBMs (21.2%). Two different types of mosaic staining were identified (1) Admixture of positive and negative nuclei or intermixed mosaic and (2) Separate fragments with positive and negative/intermixed mosaic staining. ATRX mutation was identified in 2/5 (40%) cases with mosaic staining while one case showed DAXX mutation. All these cases were characterized by distinctly separate immune-negative and positive/intermixed foci. Hence, it is suggested that cases with heterogeneous staining (especially those with distinctly negative fragments) should be subjected to mutation analysis. PMID- 26833424 TI - Seroprevalence and associated risk factors of Toxoplasma gondii infection in the Korean, Manchu, Mongol and Han ethnic groups in eastern and northeastern China. AB - A cross-sectional study was conducted from June 2013 to August 2015 to determine the seroprevalence and possible risk factors for human Toxoplasma gondii infection in Korean, Manchu, Mongol and Han ethnic groups in eastern and northeastern China. A total of 1842 serum samples, including Han (n = 802), Korean (n = 520), Manchu (n = 303) and Mongol (n = 217) groups, were analysed using enzyme-linked immunoassays to detect IgG and IgM T. gondii antibodies. The overall T. gondii IgG and IgM seroprevalences were 13.79% and 1.25%, respectively. Of these groups, Mongol ethnicity had the highest T. gondii seroprevalence (20.74%, 45/217), followed by Korean ethnicity (16.54%, 86/520), Manchu ethnicity (13.86%, 42/303) and Han ethnicity (11.35%, 98/802). Multiple analysis showed that the consumption of raw vegetables and fruits, the consumption of raw/undercooked meat and the source of drinking water were significantly associated with T. gondii infection in the Han group. Likewise, having a cat at home was identified as being associated with T. gondii infection in the Korean, Manchu and Mongol groups. Moreover, the consumption of raw/undercooked meat was identified as another predictor of T. gondii seropositivity in the Mongol group. The results of this survey indicate that T. gondii infection is prevalent in Korean, Manchu, Mongol and Han ethnic groups in the study region. Therefore, it is essential to implement integrated strategies with efficient management measures to prevent and control T. gondii infection in this region of China. Moreover, this is the first report of T. gondii infection in Korean, Manchu, and Mongol ethnic groups in eastern and northeastern China. PMID- 26833425 TI - Negotiating knowledge: parents' experience of the neuropsychiatric diagnostic process for children with autism. AB - BACKGROUND: Parents often recognize problems in their child's development earlier than health professionals do and there is new emphasis on the importance of involving parents in the diagnostic process. In Gothenburg, Sweden, over 100 children were identified as having an autism spectrum disorder (ASD) in 2009-11 through a general population language and autism screening of 2.5 year olds at the city's child healthcare centres. AIMS: To increase understanding of parents' lived experience of the neuropsychiatric diagnostic process, i.e. the period from the initial screening at age 2.5 years to the 2-year follow-up of the ASD diagnosis. METHODS & PROCEDURES: A qualitative design, a phenomenological hermeneutic method, was used. Interviews were conducted with parents of 11 children who were diagnosed with ASD 2 years prior. The parents were interviewed about their experiences of the neuropsychiatric diagnostic process, i.e. the time before the screening, the time during the neuropsychiatric multidisciplinary evaluation and the time after diagnosis. The interviews lasted for 45-130 min, and an interview guide with set questions was used. Most of the interviews were conducted at the parents' homes. OUTCOMES & RESULTS: The essence that emerged from the data was negotiating knowledge, and the three themes capturing the parents' experiences of going through the process of having their child diagnosed with ASD were seeking knowledge, trusting and challenging experts, and empowered but alone. CONCLUSIONS & IMPLICATIONS: The parents expected intervention to start directly after diagnosis but felt they had to fight to obtain the resources their child needed. After the process, they described that they felt empowered but still alone, i.e. although they received useful and important information about their child, they were left to manage the situation by themselves. As for clinical implications, the study points to the necessity of developing routines to support the parents during and after the diagnostic process. Recommended measures include developing a checklist outlining relevant contacts and agencies, establishing a coordinator responsible for each child, dividing the summary meeting at the clinic into two parts, making more than one visit to the preschool, and providing a parental training programme. PMID- 26833426 TI - Developing Korean-specific equations of stature estimation. AB - This study aims to develop Korean-specific equations for stature estimation and compare their performance to existing techniques. Due to a lack of appropriate reference samples in Korea, equations were generated using a hybrid method on 113 Korean unknown skeletons. In this approach, estimates using the anatomical method [1] were regarded as actual stature. Results revealed that new equations produced more accurate and precise estimates than previous techniques. In addition, due to consistent body proportions of Korean populations through time and space, new equations are applicable to Korean skeletons regardless of their temporal and geographic origins. For obtaining statures at death, particularly in a forensic context, an age correction factor, 0.0426 cm/year, should be applied. PMID- 26833427 TI - Multivariate multiscale complex network analysis of vertical upward oil-water two phase flow in a small diameter pipe. AB - High water cut and low velocity vertical upward oil-water two-phase flow is a typical complex system with the features of multiscale, unstable and non homogenous. We first measure local flow information by using distributed conductance sensor and then develop a multivariate multiscale complex network (MMCN) to reveal the dispersed oil-in-water local flow behavior. Specifically, we infer complex networks at different scales from multi-channel measurements for three typical vertical oil-in-water flow patterns. Then we characterize the generated multiscale complex networks in terms of network clustering measure. The results suggest that the clustering coefficient entropy from the MMCN not only allows indicating the oil-in-water flow pattern transition but also enables to probe the dynamical flow behavior governing the transitions of vertical oil-water two-phase flow. PMID- 26833428 TI - Impairment of gastric accommodation induced by water-avoidance stress is mediated by 5-HT2B receptors. AB - BACKGROUND: Psychological stress has been shown to impair gastric accommodation (GA), but its mechanism has not been elucidated. This study was conducted to clarify the role of 5-HT2B receptors in a guinea pig model of stress-induced impairment of GA. METHODS: Gastric accommodation was evaluated by measuring the intrabag pressure in the proximal stomach after administration of a liquid meal. The guinea pigs were subjected to water-avoidance stress. The role of 5-HT2B receptors in impairment of GA was investigated by administering a 5-HT2B receptor agonist (BW723C86) or antagonist (SB215505), the traditional Japanese medicine rikkunshito (RKT), a muscarinic M3 receptor antagonist (1,1-dimethyl-4 diphenylacetoxypiperidium iodide [4-DAMP]), or a nitric oxide synthase inhibitor (Nomega -nitro-L-arginine [L-NNA]). KEY RESULTS: In normal animals, liquid meal induced GA was inhibited by BW723C86, but was not affected by SB215505. The inhibition of GA by BW723C86 was reversed by co-administration of 4-DAMP. Compared to normal animals, GA in stressed animals was significantly inhibited. SB215505 and RKT significantly suppressed stress-induced impairment of GA. After meal administration, the level of cyclic guanosine monophosphate in gastric fundus tissue increased by approximately twofold in normal animals, but did not change in stressed animals. The inhibition of GA by L-NNA was suppressed by SB215505 or RKT. At a dose that did not affect GA in normal animals, BW723C86 exacerbated the impairment of GA in stressed animals. CONCLUSIONS AND INFERENCES: Stress-induced impairment of GA may be mediated by an increased responsiveness of 5-HT2B receptors, and activation of the 5-HT2B receptor signaling pathway may have an inhibitory effect on nitric oxide function. PMID- 26833429 TI - Association of Guideline-concordant Acute Asthma Care in the Emergency Department With Shorter Hospital Length of Stay: A Multicenter Observational Study. AB - OBJECTIVES: The objectives were to determine whether guideline-concordant emergency department (ED) management of acute asthma is associated with a shorter hospital length of stay (LOS) among patients hospitalized for asthma. METHODS: A multicenter chart review study of patients aged 2-54 years who were hospitalized for acute asthma at one of the 25 U.S. hospitals during 2012-2013. Based on level A recommendations from national asthma guidelines, we derived four process measures of ED treatment before hospitalization: inhaled beta-agonists, inhaled anticholinergic agents, systemic corticosteroids, and lack of methylxanthines. The outcome measure was hospital LOS. RESULTS: Among 854 ED patients subsequently hospitalized for acute asthma, 532 patients (62%) received care perfectly concordant with the four process measures in the ED. Overall, the median hospital LOS was 2 days (interquartile range = 1-3 days). In the multivariable negative binomial model, patients who received perfectly concordant ED asthma care had a significantly shorter hospital LOS (-17%, 95% confidence interval [CI] = -27% to 5%, p = 0.006), compared to other patients. In the mediation analysis, the direct effect of guideline-concordant ED asthma care on hospital LOS was similar to that of primary analysis (-16%, 95% CI = -27% to -5%, p = 0.005). By contrast, the indirect effect mediated by quality of inpatient asthma care was not significant, indicating that the effect of ED asthma care on hospital LOS was mediated through pathways other than quality of inpatient care. CONCLUSION: In this multicenter observational study, patients who received perfectly concordant asthma care in the ED had a shorter hospital LOS. Our findings encourage further adoption of guideline-recommended emergency asthma care to improve patient outcomes. PMID- 26833430 TI - Genetic Variations of NLR family genes in Behcet's Disease. AB - This study aimed to investigate whether single nucleotide polymorphisms (SNPs) of five NLR family genes (NOD1, NOD2, NLRP1, NLRP3 and CIITA) are associated with Behcet's disease (BD) in a Chinese Han population. The study was carried out in 950 BD patients and 1440 controls for 19 SNPs in the selected NLR genes. In the first-stage study, significantly decreased frequencies of the CIITA//rs12932187 C allele (Pc = 1.668E-02) and NOD1//rs2075818 G allele (Pc = 4.694E-02) were found in BD patients as compared to controls . After performing a second stage validation study and combination of data we confirmed the association of CIITA//rs12932187 and NOD1//rs2075818 with BD. In CIITA//rs12932187, the frequencies of the CC genotype and C allele were significantly lower in BD than in controls (Pc = 3.331E-06; Pc = 6.004E-07, respectively). In NOD1//rs2075818, the GG genotype and G allele showed significantly decreased frequencies in BD patients when compared to controls (Pc = 1.022E-02; Pc = 6.811E-05, respectively). Functional experiments showed that carriers with the CC genotype in CIITA//rs12932187 had a lower CIITA mRNA expression level and an enhanced IL 10 secretion as compared to GG and CG carriers. This study provides evidence that the CIITA and NOD1 gene are involved in the susceptibility to Behcet's disease. PMID- 26833431 TI - Association of Drinking Problems and Duration of Alcohol Use to Inhibitory Control in Nondependent Young Adult Social Drinkers. AB - BACKGROUND: Deficits in inhibitory control have been widely implicated in alcohol misuse. However, the literature does not readily distinguish the effects of drinking problems and chronic alcohol use. Here, we examined how years of drinking and the Alcohol Use Disorders Identification Test (AUDIT) score each influences the cerebral responses to inhibitory control in nondependent drinkers. METHODS: Fifty-seven adult drinkers and 57 age- and gender-matched nondrinkers participated in one 40-minute functional magnetic resonance imaging scan of the stop signal task. Data were preprocessed and modeled using SPM8. In a regression model, we contrasted stop and go success trials for individuals and examined activities of response inhibition each in link with the AUDIT score and years of alcohol use in group analyses. We specified the effects of duration of use by contrasting regional activations of drinkers and age-related changes in nondrinkers. In mediation analyses, we investigated how regional activities mediate the relationship between drinking problems and response inhibition. RESULTS: Higher AUDIT score but not years of drinking was positively correlated with prolonged stop signal reaction time (SSRT) and diminished responses in the cerebellum, thalamus, frontal and parietal regions, independent of years of alcohol use. Further, activity of the thalamus, anterior cingulate cortex, and presupplementary motor area significantly mediates the association, bidirectionally, between the AUDIT score and SSRT. The duration of alcohol use was associated with decreased activation in the right inferior frontal gyrus extending to superior temporal gyrus, which was not observed for age-related changes in nondrinkers. CONCLUSIONS: The results distinguished the association of drinking problems and years of alcohol use to inhibitory control in young adult nondependent drinkers. These new findings extend the imaging literature of alcohol misuse and may have implications for treatment to prevent the escalation from social to dependent drinking. More research is needed to confirm age independent neural correlates of years of alcohol use. PMID- 26833432 TI - Maturation of 5' ends of plant mitochondrial RNAs. AB - The generation of mature RNAs, i.e. mRNAs, rRNAs or tRNAs, is a complex process in all genetic systems. RNA-internal processes such as splicing or RNA editing, but also posttranscriptional processes modulating 5' and 3' termini of transcripts, contribute to RNA maturation. In this article, we focus on the posttranscriptional formation of 5' termini of mitochondrial RNAs in seed plants, with particular emphasis on the model plant species Arabidopsis thaliana (Arabidopsis). We will summarize the progress made in recent studies of proteins involved in this process. In addition, we will evaluate whether 5' processing proceeds endo- or exo-nucleolytically. Despite the considerable progress made, many details of this process remain unsolved. In particular, it is still unclear why there is frequent 5' processing of many mRNAs although impaired processing does not interfere with mitochondrial function and plant fitness. Thus, the importance of 5' processing for plant mitochondria is still puzzling. PMID- 26833434 TI - Hierarchical Zeolites with Amine-Functionalized Mesoporous Domains for Carbon Dioxide Capture. AB - To prepare materials with high CO2 adsorption, a series of hierarchical LTA zeolites possessing various mesopore spaces that are decorated with alkylamines was designed and synthesized. The highest CO2 uptake capacity was achieved when (3-aminopropyl)trimethoxysilane (APTMS) was grafted onto the hierarchical LTA zeolite having the largest mesopores. Owing to the contributions of both alkylamine groups grafted onto the mesopore surfaces and active sites in the LTA zeolites, the amount of CO2 that can be taken up on these materials is much higher than for conventional aminosilicas such SBA-15 and MCM-41. Furthermore, the adsorbent shows good CO2 uptake capacity and recyclability in dynamic flow conditions. PMID- 26833435 TI - Environmental Behaviors and Toxicities of Polycyclic Aromatic Hydrocarbons and Nitropolycyclic Aromatic Hydrocarbons. AB - Airborne particulate matter (PM) has been collected at four cities in Japan starting in the late 1990s, at five or more major cities in China, Korea and Russia starting in 2001 and at the Noto Peninsula starting in 2004. Nine polycyclic aromatic hydrocarbons (PAHs) and eleven nitropolycyclic aromatic hydrocarbons (NPAHs) were determined by HPLC with fluorescence and chemiluminescence detections, respectively. Annual concentrations of PAHs and NPAHs were in the order, China>Russia?Korea=Japan, with seasonal change (winter>summer). During the observation period, concentrations of PAHs and NPAHs in Japanese cities significantly decreased but the increases in the PAH concentration were observed in Chinese and Russian cities. Concentrations of PAHs and NPAHs were higher in the Northern China than those in the Southern China. At the Noto peninsula, which is in the main path of winter northwest winds and a year-round jet stream that blow from the Asian continent to Japan, the concentrations were high in winter and low in summer every year. A cluster analysis and back trajectory analysis indicated that PAHs and NPAHs were long range transported from Northeastern China, where coal burning systems such as coal-heating boilers are considered to be the major contributors of PAHs and NPAHs. A dramatic change in atmospheric concentrations of PAHs and NPAHs in East Asia suggests the rapid and large change of PM2.5 pollution in East Asia. Considering the adverse health effects of PM2.5, continuous monitoring of atmospheric PAHs and NPAHs is necessary in this area. PMID- 26833436 TI - Foreword. PMID- 26833437 TI - Degranulation Inhibitors from Medicinal Plants in Antigen-Stimulated Rat Basophilic Leukemia (RBL-2H3) Cells. AB - Mast cells and basophils play important roles in both immediate- and late-phase reactions of type 1 allergy. Histamine, which is released from mast cells and basophils stimulated by an antigen or degranulation inducers, is usually determined as a degranulation marker in experiments on immediate allergic reactions in vitro. beta-Hexosaminidase is also stored in secretory granules of the cells and is released concomitantly with histamine when the cells are immunologically activated, and recently this enzyme activity in the medium has been used as a marker of the degranulation. In this paper, we review our studies on the search for degranulation inhibitors, such as flavonoids, stilbenes, and curcuminoids, from medicinal plants using rat basophilic leukemia (RBL-2H3) cells. PMID- 26833433 TI - Immunotherapy of cancer: from monoclonal to oligoclonal cocktails of anti-cancer antibodies: IUPHAR Review 18. AB - Antibody-based therapy of cancer employs monoclonal antibodies (mAbs) specific to soluble ligands, membrane antigens of T-lymphocytes or proteins located at the surface of cancer cells. The latter mAbs are often combined with cytotoxic regimens, because they block survival of residual fractions of tumours that evade therapy-induced cell death. Antibodies, along with kinase inhibitors, have become in the last decade the mainstay of oncological pharmacology. However, partial and transient responses, as well as emergence of tumour resistance, currently limit clinical application of mAbs. To overcome these hurdles, oligoclonal antibody mixtures are being tested in animal models and in clinical trials. The first homo combination of two mAbs, each engaging a distinct site of HER2, an oncogenic receptor tyrosine kinase (RTK), has been approved for treatment of breast cancer. Likewise, a hetero-combination of antibodies to two distinct T-cell antigens, PD1 and CTLA4, has been approved for treatment of melanoma. In a similar vein, additive or synergistic anti-tumour effects observed in animal models have prompted clinical testing of hetero-combinations of antibodies simultaneously engaging distinct RTKs. We discuss the promise of antibody cocktails reminiscent of currently used mixtures of chemotherapeutics and highlight mechanisms potentially underlying their enhanced clinical efficacy. PMID- 26833438 TI - New Approaches to Drug Discovery for Combating MRSA. AB - Methicillin-resistant Staphylococuss aureus (MRSA) is a major nosocomial pathogen that has developed resistance to many antibiotics. New anti-infective drugs to prevent and treat MRSA infection are required. Four assay systems were conducted to screen microbial cultures for new anti-infective compounds active against MRSA. Nosokomycins, new members of the phosphoglycolipid family, were discovered from a culture of Streptomyces cyslabdanicus K04-0144 in an MRSA-silkworm infection assay. The target molecule of nosokomycins was suggested to be the transglycosylase of penicillin binding protein (PBP) involved in MRSA peptidoglycan biosynthesis. Spirohexaline, with a hexacycline structure, was isolated from a fungal culture of Penicillium brasilianum FKI-3368 in an enzyme assay of undecaprenyl pyrophosphate (UPP) synthase, which is needed for the synthesis and transport of GlcNAc-MurNAc-pentapeptides from the cytoplasmic membrane site to the external membrane site for peptidoglycan synthesis. Spirohexaline inhibited MRSA growth by the blockade of UPP synthase activity. Cyslabdan, with a cysteine-carrying labdan skeleton, was also discovered from the nosokomycin-producing actinomycete as a potentiator of imipenem activity against MRSA. The molecular target of cyslabdan was identified as FemA, which is involved in the synthesis of a pentaglycine interpeptide bridge in MRSA peptidoglycan. Citridone A with a unique 6-6/5/5-ring system containing a rare phenyl-R furopyridone skeleton, originally isolated as a potentiator of antifungal miconazole activity, was found to inhibit MRSA yellow pigment production. These new microbial products will serve as lead compounds for developing new anti infective drugs for combating MRSA. PMID- 26833439 TI - Search for Inhibitors of the Ubiquitin-Proteasome System from Natural Sources for Cancer Therapy. AB - Since the approval of the proteasome inhibitor, Velcade((r)), by the Food and Drug Administration (FDA) for the treatment of relapsed multiple myeloma, inhibitors of the ubiquitin-proteasome system have been attracting increasing attention as promising drug leads for cancer therapy. While the development of drugs for diseases related to this proteolytic system has mainly been achieved by searching libraries of synthetic small molecules or chemical modifications to drug leads, limited searches have been conducted on natural sources. We have been searching natural sources for inhibitors that target this proteolytic system through in-house screening. Our recent studies on the search for natural inhibitors of the ubiquitin-proteasome system, particularly, inhibitors against the proteasome, E1 enzyme (Uba1), E2 enzyme (Ubc13-Uev1A heterodimer), and E3 enzyme (Hdm2), and also those against deubiquitinating enzyme (USP7), are reviewed here. PMID- 26833440 TI - Bio-active Natural Products with TRAIL-Resistance Overcoming Activity. AB - Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) has emerged as a promising anticancer agent as it selectively kills cancer cells. However, TRAIL resistance limits its use as a therapeutic agent. An understanding the mechanisms responsible for TRAIL resistance and strategies to overcome it are important for its effective use as an anticancer agent. During our studies to screen natural products from medicinal plants, we identified a number of compounds with synergistic effects on TRAIL-induced apoptosis in tumor cells. This review describes our recent studies on the isolation of bioactive compounds with TRAIL resistance overcoming activity. PMID- 26833441 TI - Search for Anti-angiogenic Substances from Natural Sources. AB - As angiogenesis is critical for tumor growth and metastasis, potent and selective anti-angiogenic agents with novel modes of action are highly needed for anti cancer drug discovery. In this review, our studies focusing on the search for anti-angiogenic substances from natural sources, such as bastadins, globostellatic acid X methyl esters and cortistatins from marine sponges, and pyripyropenes from marine-derived fungus, together with senegasaponins from medicinal plant, are summarized. PMID- 26833442 TI - Evaluation of Antibacterial Activity and Reactive Species Generation of N Benzenesulfonyl Derivatives of Heterocycles. AB - Two N-benzenesulfonyl (BS) derivatives of 1,2,3,4-tetrahydroquinoline (THQ) were designed, prepared, and screened for antibacterial activity. This approach was based on combining the two privileged structures, BS and THQ, which are known to be active. The objective of this study was to evaluate the antibacterial activity of BS-THQ and its analogue 4-NH2BS-THQ, and to investigate the roles of reactive oxygen species and reactive nitrogen species in their lethality. Both showed bactericidal activity against Staphylococcus aureus ATCC 29213 and methicillin resistant S. aureus (MRSA) ATCC 43300, with transmission electron microscopy revealing a disturbed membrane architecture. Furthermore, an increase of reactive oxygen species (ROS) in strains treated with BS-THQ with respect to the control was detected when fluorescent microscopy and spectrophotometric techniques were used. The analogue 4-NH2BS-THQ demonstrated a broader spectrum of activity than BS-THQ, with a minimum inhibitory concentration of 100 ug/mL against reference strains of S. aureus, Escherichia coli and Pseudomonas aeruginosa. The assayed compounds represent promising structures for the development of new synthetic classes of antimicrobials. PMID- 26833443 TI - Chiral Recognition of Diketopiperazine Cyclo(Pro-Gly) and Propranolol Using (-) Epigallocatechin-3-O-gallate. AB - In the (1)H-NMR spectrum of a solution containing an equimolecular amount of cyclo(L-Pro-Gly), cyclo(D-Pro-Gly) and (-)-epigallocatechin-3-O-gallate (EGCg) in a D2O, a difference in the chemical shift of (1)H-NMR signal for H7alpha, H7beta,8alpha of the Pro residue was observed. Judging from the crystal structures of the 2 : 2 complexes of EGCg and cyclo(L-Pro-Gly), cyclo(D-Pro-Gly), the difference in the chemical shift resulted mainly from a magnetic anisotropic shielding effect by the ring current from the B ring of EGCg. Therefore, it was considered that chirality of cyclo(Pro-Gly) was recognized by EGCg in the D2O solution. Furthermore, in the (1)H-NMR spectrum of a solution containing an equimolecular amount of racemic propranolol ((R)- and (S)-propranolols) and EGCg in D2O, the (1)H-NMR signal for H2 of the naphthalene group was observed as two doublets, suggesting that the racemic propranolol formed diastereomers of complexes with EGCg; as a result, chirality of propranolol was recognized by EGCg in the D2O solution. PMID- 26833444 TI - Synthesis and SAR Studies of Neuritogenic Gentiside Derivatives. AB - Tetradecyl 2,3-dihydroxybenzoate (ABG-001) has been designed and synthesised as a lead compound to treat Alzheimer's disease, based on structure-activity relationships of gentisides. In this paper, the alkyl chain and ester linkage group of ABG-001 were modified. Consequently, several series of novel gentiside derivatives were designed and synthesised, and their neuritogenic activity was evaluated in PC12 cells. Among all the tested compounds, S-dodecyl 2,3 dihydroxybenzothioate (15d, named as ABG-199) was the most potent; the compound induced significant neurite outgrowth at 0.1 uM, which was comparable to that of nerve growth factor at the optimal concentration of 40 ng/mL and ABG-001 at 1 uM. A brief study on the mechanism of action of ABG-199 revealed that extracellular signal-regulated kinase phosphorylation was involved in ABG-199-induced neurite outgrowth in PC12 cells. PMID- 26833446 TI - Practical Synthesis of Pachastrissamine (Jaspine B), 2-epi-Pachastrissamine, and the 2-epi-Pyrrolidine Analogue. AB - The practical syntheses of pachastrissamine (jaspine B), 2-epi-pachastrissamine, and the 2-epimer of the pyrrolidine analogue were accomplished via the stereoselective reduction of an allylketone derived from commercially available diethyl D-tartrate and the cross-metathesis of an allyltetrahydrofuran or allypyrrolidine with 1-tridecene as key steps. PMID- 26833445 TI - Preparation of High-Payload, Prolonged-Release Biodegradable Poly(lactic-co glycolic acid)-Based Tacrolimus Microspheres Using the Single-Jet Electrospray Method. AB - Tacrolimus-loaded poly(lactic-co-glycolic acid) microspheres (TAC-PLGA-M) can be administered for the long-term survival of transplanted organs due to their immunosuppressive activity. The purpose of our study was to optimize the parameters of the electrospray method, and to prepare TAC-PLGA-M with a high payload and desirable release properties. TAC-PLGA-M were prepared using the electrospray method. In vitro characterization and evaluation were performed using scanning electron microscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy. Drug loading efficiency was greater than 80% in all formulations with a maximum loading capacity of 16.81+/-0.37%. XRD and DSC studies suggested that the drug was incorporated in an amorphous state or was molecularly dispersed in the microspheres. The in vitro release study showed prolonged release patterns. TAC PLGA-M with enhanced drug loading and prolonged-release patterns were successfully prepared using the electrospray method. PMID- 26833447 TI - Stereoselective Synthesis of Highly Functionalized 2,3-Dihydro-4-pyranones Using Phosphine Oxide as Catalyst. AB - 2,3-Dihydro-4-pyranones were synthesized stereoselectively using a chiral phosphine oxide as the catalyst. The phosphine oxide sequentially activated silicon tetrachloride and promoted the double aldol reaction of 4-methoxy-3-buten 2-one with aldehydes. Subsequent stereoselective cyclization afforded the corresponding highly functionalized 2,3-dihydro-4-pyranones bearing three contiguous chiral centers in good yields and with high diastereo- and enantioselectivities. PMID- 26833448 TI - Calcium polyphosphate particulates for bone void filler applications. AB - This study investigates the characteristics of porous calcium polyphosphate particulates (CPPp) formed using two different processing treatments as bone void fillers in non- or minimally load-bearing sites. The two calcium polyphosphate particulate variants (grades) were formed using different annealing conditions during particulate preparation to yield either more slowly degrading calcium polyphosphate particulates (SD-CPPp) or faster degrading particulates (FD-CPPp) as suggested by a previous degradation study conducted in vitro (Hu et al., Submitted for publication 2016). The two CPPp grades were compared as bone void fillers in vivo by implanting particulates in defects created in rabbit femoral condyle sites (critical size defects). The SD-CPPp and FD-CPPp were implanted for 4- and 16-week periods. The in vivo study indicated a significant difference in amount of new bone formed in the prepared sites with SD-CPPp resulting in more new bone formation compared with FD-CPPp. The lower bone formation characteristic of the FD-CPPp was attributed to its faster degradation rate and resulting higher local concentration of released polyphosphate degradation products. The study results indicate the importance of processing conditions on preparing calcium polyphosphate particulates for potential use as bone void fillers in nonload bearing sites. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 874-884, 2017. PMID- 26833449 TI - Allelobiosis in the interference of allelopathic wheat with weeds. AB - BACKGROUND: Plants may chemically affect the performance of neighbouring plants through allelopathy, allelobiosis or both. In spite of increasing knowledge about allelobiosis, defined as the signalling interactions mediated by non-toxic chemicals involved in plant-plant interactions, the phenomenon has received relatively little attention in the scientific literature. This study examined the role of allelobiosis in the interference of allelopathic wheat with weeds. RESULTS: Allelopathic wheat inhibited the growth of five weed species tested, and the allelochemical (2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one) production of wheat was elicited in the presence of these weeds, even with root segregation. The inhibition and allelochemical levels varied greatly with the mixed species density. Increased inhibition and allelochemical levels occurred at low and medium densities but declined at high densities. All the root exudates and their components of jasmonic acid and salicylic acid from five weeds stimulated allelochemical production. Furthermore, jasmonic acid and salicylic acid were found in plants, root exudates and rhizosphere soils, regardless of weed species, indicating their participation in the signalling interactions defined as allelobiosis. CONCLUSION: Through root-secreted chemical signals, allelopathic wheat can detect competing weeds and respond by increased allelochemical levels to inhibit them, providing an advantage for its own growth. Allelopathy and allelobiosis are two probably inseparable processes that occur together in wheat weed chemical interactions. (c) 2016 Society of Chemical Industry. PMID- 26833450 TI - Comparative studies of the composition of bacterial microbiota associated with the ruminal content, ruminal epithelium and in the faeces of lactating dairy cows. AB - The objective of this research was to compare the composition of bacterial microbiota associated with the ruminal content (RC), ruminal epithelium (RE) and faeces of Holstein dairy cows. The RC, RE and faecal samples were collected from six Holstein dairy cows when the animals were slaughtered. Community compositions of bacterial 16S rRNA genes from RC, RE and faeces were determined using a MiSeq sequencing platform with bacterial-targeting universal primers 338F and 806R. UniFrac analysis revealed that the bacterial communities of RC, RE and faeces were clearly separated from each other. Statistically significant dissimilarities were observed between RC and faeces (P = 0.002), between RC and RE (P = 0.003), and between RE and faeces (P = 0.001). A assignment of sequences to taxa showed that the abundance of the predominant phyla Bacteroidetes was lower in RE than in RC, while a significant higher (P < 0.01) abundance of Proteobacteria was present in RE than in RC. When compared with the RC, the abundance of Firmicutes and Verrucomicrobia was higher in faeces, and RC contained a greater abundance of Bacteroidetes and Tenericutes. A higher proportions of Butyrivibrio and Campylobacter dominated RE as compared to RC. The faecal microbiota was less diverse than RC and dominated by genera Turicibacter and Clostridium. In general, these findings clearly demonstrated the striking compositional differences among RC, RE and faeces, indicating that bacterial communities are specific and adapted to the harbouring environment. PMID- 26833451 TI - Viability, morphology, and proteome of Mycobacterium smegmatis MSMEG_0319 knockout strain. AB - Mycobacterium tuberculosis Rv0228, a membrane protein, is predicted as a drug target through computational methods. MSMEG_0319 (MS0319) in Mycobacterium smegmatis mc(2) 155 is the ortholog of Rv0228. To study the effect of MS0319 protein on M. smegmatis, an MS0319 gene knockout strain (DeltaMS0319) was generated via a homologous recombination technique in this study. The results showed that the lack of MS0319 protein in mc(2) 155 cells led to the loss of viability at nonpermissive temperature. Scanning electron microscopy and transmission electron microscopy observations showed drastic changes in cellular shape especially cell wall disruption in DeltaMS0319 cells. Proteomic analysis of DeltaMS0319 cells through LC-MS/MS revealed that 462 proteins had changes in their expressions by lacking MS0319 protein. The M. tuberculosis orthologs of these 462 proteins were found through BLASTp search and functional clustering and metabolic pathway enrichment were performed on the orthologs. The results revealed that most of them were enzymes involved in metabolism of carbohydrates and amino acids, indicating that Rv0228 played an important role in cellular metabolism. All these results suggested Rv0228 as a potential target for development of antituberculosis drugs. PMID- 26833452 TI - RNA Hairpin Folding in the Crowded Cell. AB - Precise secondary and tertiary structure formation is critically important for the cellular functionality of ribonucleic acids (RNAs). RNA folding studies were mainly conducted in vitro, without the possibility of validating these experiments inside cells. Here, we directly resolve the folding stability of a hairpin-structured RNA inside live mammalian cells. We find that the stability inside the cell is comparable to that in dilute physiological buffer. On the contrary, the addition of in vitro artificial crowding agents, with the exception of high-molecular-weight PEG, leads to a destabilization of the hairpin structure through surface interactions and reduction in water activity. We further show that RNA stability is highly variable within cell populations as well as within subcellular regions of the cytosol and nucleus. We conclude that inside cells the RNA is subject to (localized) stabilizing and destabilizing effects that lead to an on average only marginal modulation compared to diluted buffer. PMID- 26833453 TI - Motivation for physical activity and exercise in severe mental illness: A systematic review of cross-sectional studies. AB - Individuals with severe mental illness (SMI) are less physically active than the general population. One important barrier contributing to this inactivity is lack of motivation. The aim of this paper is to systematically review all cross sectional literature on motivation for physical activity among people with SMI and to use the results as basis for guidance on how mental health nurses can facilitate motivation for physical activity. Systematic searches of seven databases were conducted from database inception to February 2015. Studies were eligible if they included participants with SMI and reported data on motivation for physical activity. In total, 21 articles were included and over half them were published in 2011 or later. The present results indicate preliminary evidence of how the motivational processes do not differ between individuals with SMI and the general population, and that they are independent of diagnosis, medication, age, gender, and body mass index. Results from the current systematic review can give some tentative guidance on how to facilitate motivation for physical activity within mental health-care. However, there is still a great need for developing and examining practical strategies that can enhance adoption and adherence of physical activity among people with SMI. PMID- 26833454 TI - Combined use of two formulations containing diacetyl boldine, TGF-beta1 biomimetic oligopeptide-68 with other hypopigmenting/exfoliating agents and sunscreen provides effective and convenient treatment for facial melasma. Either is equal to or is better than 4% hydroquinone on normal skin. AB - BACKGROUND: Treatment of melasma remains a challenge and involves multistep approach. Diacetyl boldine (DAB) stabilizes tyrosinase in its inactive form while TGF-beta1 biomimetic oligopeptide-68 inhibits tyrosinase activity. AIMS: (1) to study the efficacy and safety of the combination use of two formulae containing two principal ingredients: DAB and TGF-beta1 biomimetic oligopeptide-68 on facial melasma, and (2) to compare their efficacy with 2% and 4% hydroquinone cream (HQ) on sun-protected normal skin. METHODS: A randomized, double-blind, 12-week comparative study of pre-/post-treatment was conducted in 40 females. Melasma was evaluated by manual MASI score and MASI score with instrumentally graded darkness at baseline, 6th week, and 12th week. The author also compared their effect with HQ on the arms, assessed their safety profile throughout the study. RESULTS: Thirty-eight subjects have completed the study. Their melasma showed improvement at the 6th week and 12th week as compared with baseline (P < 0.05). None developed severe reaction. Most subjects had temporary, mild skin reaction. About 2.6% of subjects graded themselves markedly improved, 76.3% moderately improved, and 21.1% slightly improved. Each formula showed either more efficacy or exerted faster action on pigment reduction than HQ. CONCLUSION: Combination of DAB serum at night and DAB/TGF-beta1 biomimetic oligopeptide-68/sunscreen cream in the morning and at noon was effective and safe for facial melasma. They were superior to HQ in pigment reduction. PMID- 26833455 TI - Superior anti-CO poisoning capability: Au-decorated PtFe nanocatalysts for high performance methanol oxidation. AB - Herein we demonstrate a surface engineering strategy, namely, decorating Au on the surface of bimetallic PtFe nanocatalysts, to effectively decrease the adsorption energy of CO on the Pt center, which promotes the electrocatalytic activity towards methanol oxidation, far better than those of PtFe and commercial Pt/C catalysts. PMID- 26833457 TI - Patient preferences for route of allergy immunotherapy: a comparison of four delivery methods. AB - BACKGROUND: Allergen-specific immunotherapy (IT) is a disease-modifying treatment for allergic rhinitis, and adherence to the treatment schedule is important for a successful outcome. Several methods for delivering IT are now available, but little information is known concerning patient preference for these options. METHODS: Over a 12-month period, 228 adults scheduled to undergo outpatient allergy testing were offered a survey to rank 4 different IT delivery methods: subcutaneous IT (SCIT), sublingual IT using liquid extracts (SLIT), sublingual allergy immunotherapy tablets (AIT), and oral mucosal immunotherapy (OMIT) using a toothpaste delivery vehicle. RESULTS: Of the participants who completed the survey, ranking scores (mean +/- SD) for SCIT, SLIT, AIT, and OMIT, with 1 being the highest rank, were 3.36 +/- 1.02, 2.03 +/- 0.92, 2.30 +/- 1.02, and 2.32 +/- 1.05, respectively. The number of participants who ranked SCIT, SLIT, AIT, or OMIT as their number 1 choice was 24 (10.5%), 79 (34.6%), 61 (26.8%), and 64 (28.1%), respectively. When comparing first choice rankings, there were no statistically significant differences between SLIT, AIT, or OMIT, yet all 3 groups ranked higher than SCIT (p < 0.0001). CONCLUSION: SCIT earned the lowest mean rank and had the least number of participants rank it as the most preferred method. Among the other 3 choices, by mean scores, SLIT was preferred most compared to either AIT or OMIT; but when considering first choices only, there were no significant differences in preference. Most of the study participants identified the convenience of home IT administration as the most important factor in their ranking. PMID- 26833456 TI - Analysis of fluid movement in skeletal muscle using fluorescent microspheres. AB - INTRODUCTION: Regional variability in interstitial fluid pressure confounds use of intramuscular pressure measurement to assess muscle force. It is hypothesized that interstitial flow is dependent on intramuscular pressure. The goal of this study was to assess the feasibility of using fluorescent microspheres to evaluate movement of interstitial fluid in skeletal muscle. METHODS: Two diameters of fluorescent microspheres were injected into the rat tibialis anterior during both static (n = 6) and passively lengthened (10% strain) experimental conditions (n = 6). Microsphere dispersion was evaluated using confocal imaging of transverse muscle sections. RESULTS: Fluorescent microspheres tracked interstitial fluid while not penetrating the muscle fiber. When compared with the static condition, significantly greater dispersion (P = 0.003) was seen with passively lengthened conditions (17 +/- 9% vs. 31 +/- 7%, respectively). Dispersion did not differ for the 2 microsphere sizes (P = 0.811). CONCLUSIONS: Fluorescent microspheres track movement of interstitial fluid, and dispersion is dependent on passive lengthening. Muscle Nerve 54: 444-450, 2016. PMID- 26833461 TI - Study on rectal administration of azithromycin by suppository for pediatric use. AB - OBJECTIVE: Azithromycin (AZM) is widely used as a first-line treatment option for children with mycoplasma pneumonia. Although pharmacists perform medication counseling in the pediatric ward, children often experience vomiting as a result of oral AZM administration. Drugs that are administered rectally are generally considered to enter the circulation system without passing through the liver first. The aim of our study was to prepare an AZM suppository and investigate the pharmaceutical properties and well as pharmacokinetics of the rectal administration route in humans. MATERIALS AND METHODS: Five healthy volunteers were enrolled in the study. All subjects provided written informed consent before participating in the study. Subjects were randomly assigned to either oral administration of oral AZM 500-mg tablet or rectal administration of 125-mg, 250 mg, or 500-mg AZM suppository. Blood samples for preparation of serum were collected predose as well as at 1, 2, 3, 4, 6, 12, and 24 hours following the first rectal dose. Serum concentrations of AZM were determined by high performance liquid chromatography (HPLC) with electrochemical detection. RESULTS AND CONCLUSION: The bioavailability of the AZM suppository through rectal administration was 20.3% compared to oral administration. We hypothesize that the surface area where AZM is absorbed also affects the absorption by rectal administration. Although further investigation is necessary to improve the absorption of AZM by the rectum and to ensure safety in children, the AZM suppository may be an effective preparation in cases where oral administration is not tolerated. PMID- 26833462 TI - Safety, PK, and PD of recombinant anti-interleukin-21 monoclonal antibody in a first-in-human trial. AB - OBJECTIVE: This first-in-human, randomized, double-blind, placebo-controlled trial assessed the safety of NNC0114-0005, a human recombinant anti interleukin (IL)-21 monoclonal antibody, for the treatment of rheumatoid arthritis (RA). METHODS AND MATERIALS: Healthy male subjects (HS (n = 44)) and patients with active RA treated with methotrexate (n = 20) were randomized 3 : 1 to single IV or SC doses of NNC0114-0005 (0.0025 - 25 mg/kg) or placebo. Safety endpoints, pharmacokinetics, and pharmacodynamics were assessed over 12 weeks. RESULTS: All study participants were analyzed. 37 AEs were reported in 21 NNC0114-0005-treated participants (44%) and 18 AEs in 10 placebo-treated participants (63%), with no dose-dependency. The most common AEs were headache and nasopharyngitis; there were no injection-site reactions Linear pharmacokinetics of NNC0114-0005 were indicated (mean terminal half-life, 2 - 3 weeks). Dose-dependent total IL-21 (free IL-21 and IL-21-NNC0114-0005 complexes) accumulation was observed. Preliminary signs of reduced RA activity were observed with 25 mg/kg NNC0114 0005. CONCLUSIONS: Single doses of NNC0114-0005 (<= 25 mg/kg IV; <= 4 mg/kg SC) were well tolerated in HS and patients with RA. Accumulation of IL-21-containing complexes suggests neutralization of the target cytokine. Based< on this trial, further trials to explore the efficacy of anti-IL-21 were initiated. PMID- 26833464 TI - Focus on wrist injuries. PMID- 26833463 TI - Management of high-grade renal injury in children. AB - INTRODUCTION: The management of severe renal trauma is disputable. Herein, we present diagnosis and treatment of patients with high-grade renal injury (grades IV and V). MATERIALS AND METHODS: The records of 31 patients with severe renal trauma who were treated between 2009 and 2014 were analyzed retrospectively. All patients' CT results were evaluated by two radiologists and assigned grades of IV or V in accordance with the American Association for the Surgery of Trauma Organ Injury Severity Scale. All hemodynamically stable renal trauma patients were treated conservatively. Patients with renal traumas of grade IV and V were evaluated statistically via the SPSS 15.0 software program. Chi-square and Mann Whitney U tests were used to evaluate the categorical data. RESULTS: Thirteen (42 %) of 31 patients had grade IV, and 18 (58 %) had grade V renal traumas. Twenty seven (87 %) of the patients had suffered blunt trauma, and four (13 %) had sustained penetrating injuries. Additional organ injuries were seen in 16 patients (52 %), and 15 (48 %) had no concurrent injuries. Twenty-five patients (89 %) were monitored conservatively, three (10 %) underwent surgery, and three patients with grade V renal trauma and additional organ injuries died. There was no statistically significant difference between the grade IV and grade V groups, except in hemoglobin values and the affected kidney (P = 0.07 and P = 0.02, respectively). CONCLUSIONS: Computerized tomography can help to grade renal injury and assess additional organ injuries quickly. Most children with high grade renal injury can be managed conservatively. However, conservative management of renal traumas relies on a multidisciplinary approach. Additionally, surgical intervention is generally required in the face of hemodynamic instability or other concurrent organ injuries. PMID- 26833465 TI - Dependence of Gene-by-Environment Interactions (GxE) on Scaling: Comparing the Use of Sum Scores, Transformed Sum Scores and IRT Scores for the Phenotype in Tests of GxE. AB - Estimates of gene-environment interactions (GxE) in behavior genetic models depend on how a phenotype is scaled. Inappropriately scaled phenotypes result in biased estimates of GxE and can sometimes even suggest GxE in the direction opposite to its true direction. Previously proposed solutions are mathematically complex, computationally demanding and may prove impractical for the substantive researcher. We, therefore, evaluated two simple-to-use alternatives: (1) straightforward non-linear transformation of sum scores and (2) factor scores from an appropriate item response theory (IRT) model. Within Purcell's (2002) GxM framework, both alternatives provided less biased parameter estimates, and improved false and true positive rates than using a raw sum score. These approaches are, therefore, recommended over using raw sum scores in tests of GxE. Circumstances under which IRT factor scores versus transformed sum scores should be preferred are discussed. PMID- 26833466 TI - Disconnectedness from the here-and-now: a phenomenological perspective as a counteract on the medicalisation of death wishes in elderly people. AB - When elderly people are ideating on manners to end their lives, because they feel life is over and no longer worth living, it is important to understand their lived experiences, thoughts and behaviour in order to appropriately align care, support and policy to the needs of these people. In the literature, the wish to die in elderly people is often understood from a medical, psychopathological paradigm, referred to as cognitive impairment, depressive disorder, pathological bereavement, and suicidality. In this paper, we evaluate this dominant paradigm by considering three serious limitations, namely: (1) the risk of epistemic transformation; (2) the risk of reduction; and (3) the risk of obscuring the social and cultural embeddedness. Drawing on insights from our empirical phenomenological research on the issue of elderly and the self-chosen death, this paper argues for a phenomenological perspective to counteract the medicalisation of death wishes in elderly people. PMID- 26833468 TI - IFN-gamma activated sites in the survivin gene promoter region: the point of no return of cytokine-induced pancreatic beta-cells death? PMID- 26833467 TI - How do researchers decide early clinical trials? AB - Launch of clinical investigation represents a substantial escalation in commitment to a particular clinical translation trajectory; it also exposes human subjects to poorly understood interventions. Despite these high stakes, there is little to guide decision-makers on the scientific and ethical evaluation of early phase trials. In this article, we review policies and consensus statements on human protections, drug regulation, and research design surrounding trial launch, and conclude that decision-making is largely left to the discretion of research teams and sponsors. We then review what is currently understood about how research teams exercise this discretion, and close by laying out a research agenda for characterizing the way investigators, sponsors, and reviewers approach decision-making in early phase research. PMID- 26833469 TI - Hot pelvic exenteration: is it worth it? PMID- 26833470 TI - To drain or not to drain in colorectal anastomosis: a meta-analysis. AB - BACKGROUND: Currently, many surgeons place a prophylactic drain in the abdominal or pelvic cavity after colorectal anastomosis as a conventional treatment. However, some trials have demonstrated that this procedure may not be beneficial to the patients. OBJECTIVE: To determine whether prophylactic placement of a drain in colorectal anastomosis can reduce postoperative complications. METHODS: We systematically searched all the electronic databases for randomized controlled trials (RCTs) that compared routine use of drainage to non-drainage regimes after colorectal anastomosis, using the terms "colorectal" or "colon/colonic" or "rectum/rectal" and "anastomo*" and "drain or drainage." Reference lists of relevant articles, conference proceedings, and ongoing trial databases were also screened. Primary outcome measures were clinical and radiological anastomotic leakage. Secondary outcome measures included mortality, wound infection, re operation, and respiratory complications. We assessed the eligible studies for risk of bias using the Cochrane Risk of Bias Tool. Two authors independently extracted data. RESULTS: Eleven RCTs were included (1803 patients in total, 939 patients in the drain group and 864 patients in the no drain group). Meta analysis showed that there was no statistically significant differences between the drain group and the no drain group in (1) overall anastomotic leakage (relative risk (RR) = 1.14, 95 % confidence interval (CI) 0.80-1.62, P = 0.47), (2) clinical anastomotic leakage (RR = 1.39, 95 % CI 0.80-2.39, P = 0.24), (3) radiologic anastomotic leakage (RR = 0.92, 95 % CI 0.56-1.51, P = 0.74), (4) mortality (RR = 0.94, 95 % CI 0.57-1.55, P = 0.81), (5) wound infection (RR = 1.19, 95 % CI 0.84-1.69, P = 0.34), (6) re-operation (RR = 1.18, 95 % CI 0.75 1.85, P = 0.47), and (7) respiratory complications (RR = 0.82, 95 % CI 0.55-1.23, P = 0.34). CONCLUSIONS: Routine use of prophylactic drainage in colorectal anastomosis does not benefit in decreasing postoperative complications. PMID- 26833472 TI - Sacral nerve stimulation--hidden costs (uncovered). AB - AIM: The aim of this study is to determine the occurrence of surgical revision in a cohort of patients treated with sacral nerve stimulation (SNS) for faecal incontinence and constipation and to establish the types of procedures performed and indications for surgery. METHOD: From the years 2002 to 2014, 125 patients were identified who had undergone permanent SNS therapy with 36 (28.8 %) patients requiring surgical intervention postimplantation. These cases were retrospectively reviewed (range of follow-up 1-99 months). RESULTS: Over a total of 1512 months of SNS treatment, 51 unplanned surgical procedures were required in 36 patients. At present, 48 procedures have been performed at an average of 2.6 years following implantation and three patients are awaiting surgery. Lead related problems accounted for 30 (58.8 %) procedures at an average of 1.7 years affecting 22 patients. Battery and implantable pulse generator-related problems attributed to 13 procedures (25.5 %) in 12 patients at an average of 5.0 years. Battery depletion occurred in seven patients at an average of 5.4 years. Surgical revision was required to replace, remove, or resite various components of the SNS system. Indications for surgery included lead damage, pain and loss or lack of SNS efficacy. Explantation was warranted in six patients due to poor SNS efficacy, pain, infection and facilitation of a magnetic resonance imaging scan. This was performed at an average of 1.6 years. CONCLUSION: A considerable proportion of patients treated with SNS therapy require surgical revision. These unplanned procedures are associated with substantial unexpected costs that financially burden SNS services. PMID- 26833471 TI - Complete mesocolic excision and extended (D3) lymphadenectomy for colonic cancer: is it worth that extra effort? A review of the literature. AB - PURPOSE: Recent interest in complete mesocolic excision (CME) with central vascular ligation (CVL) or extended (D3) lymphadenectomy (EL) for curative resection of colon cancer has been driven by published series from experienced practitioners showing excellent survival outcomes and low recurrence rates. In this article, we attempt to clarify the role of CME or EL in modern colorectal surgery. METHODS: A narrative review of the evidence for CME and EL in the curative treatment of colon cancer. RESULTS: The principal of CME surgery, similar to total mesorectal excision (TME) for rectal cancer, is the removal of all lymphatic, vascular, and neural tissue in the drainage area of the tumour in a complete mesocolic envelope with intact mesentery, peritoneum and encasing fascia. Extended (D3) lymphadenectomy (EL) is based on similar principles. Sound anatomical and oncological arguments are made to support the principles of removing the tumor contained within an intact mesocolic facial envelope together with an extended lymph node harvest. Excellent oncological outcomes with minimal morbidity and mortality have been reported. This has led to calls for the standardisation of surgery for colon cancer using CME. However, there is conflicting evidence regarding the prognostic benefit of greater lymph node harvests and the evidence for an oncological benefit of CME is limited by methodology flaws and several potential confounding factors. CONCLUSIONS: Although there is a reasonable anatomical and oncological basis for these techniques, there are no randomised controlled trials from which to draw confident conclusions and there is insufficient consistent high quality evidence to recommend widespread adoption of CME. PMID- 26833473 TI - Ileocecal valve preservation in a 58-year-old Crohn's disease patient. PMID- 26833475 TI - Comparison of endoscopic incision and endoscopic balloon dilation for the treatment of refractory colorectal anastomotic strictures. PMID- 26833476 TI - da Vinci robotic versus laparoscopic surgery in rectal cancer: a meta-analysis of postsurgery complications. PMID- 26833474 TI - Totally robotic rectal resection: an experience of the first 100 consecutive cases. AB - INTRODUCTION: Robotic surgery provides an alternative option for a minimal access approach. It provides a stable platform with high definition three-dimensional views and improved access, which enhances the capabilities for precise dissection in a narrow surgical field. These distinctive features have made it an attractive option for colorectal surgeons. AIM: The aim of this study was to present a standardised technique for single-docking robotic rectal resection and to analyse clinical outcomes of the first 100 robotic rectal procedures performed in a single centre between May 2013 and April 2015. METHOD: Prospectively collected data related to 100 consecutive patients who underwent single-docking robotic rectal surgery was analysed for surgical and oncological outcomes. RESULTS: Sixty six patients were male, the median age was 67 years (range-24-92). Eighteen patients had neo-adjuvant chemoradiotherapy whilst 23 patients had BMI >30. Procedures performed included anterior resection (n = 74), abdominoperineal resection (n = 10), completion proctectomy (n = 9), restorative proctectomy with ileal pouch-anal anastomosis (IPAA) (n = 5) and Hartmann's procedure (n = 2). The median operating time was 240 min (range-135-456), and median blood loss was 10 ml (range 0-200). There was no conversion or intra-operative complication. Median length of stay was 7 days (range, 3-48) and readmission rate was 12 %. Thirty-day mortality was zero. Postoperatively, two patients had an anastomotic leak whilst two had small bowel obstruction. The median lymph node harvest was 18 (range, 6 43). CONCLUSION: The single-docking robotic technique should be considered as an alternative option for rectal surgery. This approach is safe and feasible and in our study it has demonstrated favourable clinical outcomes. PMID- 26833477 TI - Clinical severity of fecal incontinence after anorectal surgery and its relationship with endoanal ultrasound features. PMID- 26833478 TI - Amorolfine 5% Nail Lacquer Exhibits Potent Antifungal Activity Compared to Three Acid-Based Devices Indicated for the Treatment of Onychomycosis: An In Vitro Nail Penetration Assay. AB - INTRODUCTION: Onychomycosis is the most common infectious disease involving nails. The aim of this study was to evaluate the antifungal activity of amorolfine 5% nail lacquer and three different acid-based medical devices indicated in the treatment of onychomycosis using an in vitro nail penetration assay. METHODS: Four products were tested in vitro: (a) amorolfine 5% nail lacquer; (b) ethyl lactate and acetic acid; (c) citric acid and urea; (d) ethyl lactate, glycerin, lactic acid, and citric acid. Test products were applied to healthy human cadaver nails and allowed to dry. Disks were cut from each piece of nail and placed on seeded agar plates of Trichophyton rubrum. Following incubation at 30 degrees C, zones of inhibition were measured. RESULTS: Amorolfine-treated nails exhibited inhibitory activity against T. rubrum with a mean zone of inhibition of 59.2 mm in diameter. In contrast, all three acid-based medical devices and the untreated controls showed no zones of inhibition (mean effective zones of 0 mm). CONCLUSION: In this in vitro nail penetration model, head-on, comparative study, we showed that amorolfine 5% nail lacquer possesses potent antifungal activity, whereas no antifungal activity was detected for three commercially available acid-based medical devices under identical assay conditions. FUNDING: Galderma. PMID- 26833479 TI - Role of Metallothionein in Post-Burn Inflammation. AB - Metallothioneins (MTs) are a family of low molecular-weight and cysteine-rich metalloproteins that regulate metal metabolism and protect cells from oxygen free radicals. Recent studies suggested that MTs have some anti-inflammatory effects. However, the role of MTs in post-burn inflammation remains unclear. This study is designed to investigate the role of MTs in post-burn inflammation in a mouse burn model. MT-I/II null (-/-) and C57BL/6 wild-type (WT) mice were randomly divided into sham burn, burn, Zn treated, and Zn-MT-2 treated groups. The inflammatory cytokines levels were measured by enzyme-linked immunosorbent assay (ELISA). Myeloperoxidase (MPO) activity was determined by spectrophotometry. In in vitro study, exogenous MT-2 was added to macrophages that were stimulated with burn serum in the presence or absence of a p38 MAPK inhibitor SB203580. The IL-6 and TNF-alpha messenger RNA (mRNA) expression were detected by quantitative real-time polymerase chain reaction. The levels of p38 expression were determined by Western blot. Burn induced increased inflammatory cytokines such as interleukin (IL)-1beta, IL-6, tumor necrosis factors-alpha, and macrophage chemoattractant protein-1 production in burn wound and serum. The MPO activities in the lung and heart were also increased after burn. These effects were significantly more prominent in MT (-/-) mice than in WT mice. Furthermore, these effects were inhibited by administration of exogenous MT-2 to both WT and MT (-/-) mice. Exogenous MT-2 inhibited the p38 expression and abrogated the increase of IL-6 and TNF-alpha mRNA expression from macrophages that were stimulated with burn serum. The effect of MT-2 was not further strengthened in the presence of SB203580. MTs may have a protective role against post-burn inflammation and inflammatory organ damage, at least partly through inhibiting the p38 MAPK signaling. PMID- 26833480 TI - Telomerase activity in breast cancer patients: association with poor prognosis and more aggressive phenotype. AB - Telomerase expression is an important mechanism of tumor unlimited replicative potential. The aim of this study was to evaluate prognostic impact of telomerase activity in breast cancer patients and to correlate telomerase activity with established prognostic factors. We analyzed tissue of 102 malignant breast lesions and 20 healthy breast tissues. Telomerase activity was determined by telomeric repeat amplification protocol assay. Telomerase activity was present in 77 (75.49 %) of 102 breast cancers. Telomerase activity in breast cancers was statistically significantly higher in comparison with the activity in normal breast tissue. The levels of telomerase activity were significantly positively correlated with tumor size, axillary nodal status, histological grade, HER-2/neu protein expression in tumor tissue and expression of the nuclear antigen Ki-67. A statistically significant negative correlation was found between the presence of ER and telomerase activity. There was no correlation between telomerase activity and concentration of PR or the age of patients. Kaplan-Meier analysis showed that patients with higher telomerase activity had significantly shorter 10-year disease-free survival (p < 0.0001) and 10-year overall survival (p < 0.0001) than those with lower telomerase activity. These results were confirmed by logistic regression analysis. Our results support the prognostic role of telomerase activity and its relationship with the more aggressive phenotype of breast cancer. PMID- 26833482 TI - Role of percutaneous abscess drainage in the management of young patients with Crohn disease. AB - BACKGROUND: Intra-abdominal abscess is a common complication of Crohn disease in children. Prior studies, primarily in adults, have shown that percutaneous abscess drainage is a safe and effective treatment for this condition; however, the data regarding this procedure and indications in pediatric patients is limited. OBJECTIVE: Our aim was to determine the success rate of percutaneous abscess drainage for abscesses related to Crohn disease in pediatric patients with a focus on treatment endpoints that are relevant in the era of biological medical therapy. MATERIALS AND METHODS: We retrospectively reviewed 25 cases of patients ages <=20 years with Crohn disease who underwent percutaneous abscess drainage. Technical success was defined as catheter placement within the abscess with reduction in abscess size on post-treatment imaging. Clinical success was defined as (1) no surgery within 1 year of drainage or (2) surgical resection following drainage with no residual abscess at surgery or on preoperative imaging. Multiple clinical parameters were analyzed for association with treatment success or failure. RESULTS: All cases were classified as technical successes. Nineteen cases were classified as clinical successes (76%), including 7 patients (28%) who required no surgery within 1 year of percutaneous drainage and 12 patients (48%) who had elective bowel resection within 1 year. There was a statistically significant association between resumption of immunosuppressive therapy within 8 weeks of drainage and both clinical success (P < 0.01) and avoidance of surgery after 1 year (P < 0.01). CONCLUSION: Percutaneous abscess drainage is an effective treatment for Crohn disease-related abscesses in pediatric patients. Early resumption of immunosuppressive therapy is statistically associated with both clinical success and avoidance of bowel resection, suggesting a role for percutaneous drainage in facilitating prompt initiation of medical therapy and preventing surgical bowel resection. PMID- 26833483 TI - Different evolutionary patterns of SNPs between domains and unassigned regions in human protein-coding sequences. AB - Protein evolution plays an important role in the evolution of each genome. Because of their functional nature, in general, most of their parts or sites are differently constrained selectively, particularly by purifying selection. Most previous studies on protein evolution considered individual proteins in their entirety or compared protein-coding sequences with non-coding sequences. Less attention has been paid to the evolution of different parts within each protein of a given genome. To this end, based on PfamA annotation of all human proteins, each protein sequence can be split into two parts: domains or unassigned regions. Using this rationale, single nucleotide polymorphisms (SNPs) in protein-coding sequences from the 1000 Genomes Project were mapped according to two classifications: SNPs occurring within protein domains and those within unassigned regions. With these classifications, we found: the density of synonymous SNPs within domains is significantly greater than that of synonymous SNPs within unassigned regions; however, the density of non-synonymous SNPs shows the opposite pattern. We also found there are signatures of purifying selection on both the domain and unassigned regions. Furthermore, the selective strength on domains is significantly greater than that on unassigned regions. In addition, among all of the human protein sequences, there are 117 PfamA domains in which no SNPs are found. Our results highlight an important aspect of protein domains and may contribute to our understanding of protein evolution. PMID- 26833481 TI - STAT3 polymorphism rs4796793 may be a predictive factor of tumor response to multiple tyrosine kinase inhibitors in metastatic renal cell carcinoma in Japanese population. AB - Signal transducer and activator of transcription (STAT) 3 is a key factor in multiple tyrosine kinase inhibitor (mTKI)-induced growth inhibition and apoptosis of renal cell carcinoma (RCC) cells. This study aimed to identify associations between single-nucleotide polymorphisms (SNPs) in the STAT3 gene and tumor response to mTKIs in patients with metastatic RCC (mRCC). Seventy-one patients with clear cell RCC treated with any mTKI were retrospectively genotyped to elucidate a potential association between STAT3 SNPs and overall best response to drugs. Of 50 patients included for analysis, a partial or complete response was observed in 17. A significant association was found between rs4796793 alleles and tumor response [G vs. C, odds ratio (OR) 3.25, 95 % confidence interval (CI) 1.30 8.07]. There were a higher percentage of responders with the C/C genotype at rs4796793 than with the G/C + G/G genotypes (OR 4.46, 95 % CI 1.31-15.28). Time to-event analysis demonstrated a statistically significant difference between patients with the CC genotype and those with G/C + G/G genotypes in time-to treatment response, but not in progression-free survival or time-to-treatment failure. The rs4796793 genotype is a novel predictive factor of the response to mTKIs in patients with mRCC. However, prospective translational trials with larger patient cohorts are required to confirm these results. PMID- 26833484 TI - Genome-wide analysis of CrRLK1L gene family in Gossypium and identification of candidate CrRLK1L genes related to fiber development. AB - Members of the CrRLK1L family, a subgroup of the receptor-like kinase (RLK) gene family, are thought to act as sensors for the integrity of the cell wall and regulators of polar elongation. To better understand the various functions in fiber development, we conducted genome-wide identification and characterization analyses of CrRLK1L family in cotton. Here 44, 40, and 79 CrRLK1L genes were identified from three cotton species: diploid G. raimondii (D5), diploid G. arboreum (A2), and tetraploid G. hirsutum TM-1 (AD1), respectively. The 44 CrRLK1Ls in G. raimondii were anchored to the 12 chromosomes unevenly and were classified into six groups (I-VI), with group II and group IV being further divided into two subgroups (groups IIa and IIb, and IVa and IVb, respectively). These CrRLK1Ls displayed a highly regular pattern of developmental and spatial regulation in cotton. Using the transcriptome data of five chromosomal segment introgression lines (CSILs) and the physical integration of CrRLK1Ls with the quantitative trait loci (QTLs) related to fiber quality traits, we revealed that six CrRLK1L genes were highly associated with fiber development. This study brings new insights into the integrated genome-wide identification of CrRLK1Ls in cotton and provides references for the genetic improvement of cotton fiber. PMID- 26833485 TI - A cis-regulatory sequence from a short intergenic region gives rise to a strong microbe-associated molecular pattern-responsive synthetic promoter. AB - The high gene density in Arabidopsis thaliana leaves only relatively short intergenic regions for potential cis-regulatory sequences. To learn more about the regulation of genes harbouring only very short upstream intergenic regions, this study investigates a recently identified novel microbe-associated molecular pattern (MAMP)-responsive cis-sequence located within the 101 bp long intergenic region upstream of the At1g13990 gene. It is shown that the cis-regulatory sequence is sufficient for MAMP-responsive reporter gene activity in the context of its native promoter. The 3' UTR of the upstream gene has a quantitative effect on gene expression. In context of a synthetic promoter, the cis-sequence is shown to achieve a strong increase in reporter gene activity as a monomer, dimer and tetramer. Mutation analysis of the cis-sequence determined the specific nucleotides required for gene expression activation. In transgenic A. thaliana the synthetic promoter harbouring a tetramer of the cis-sequence not only drives strong pathogen-responsive reporter gene expression but also shows a high background activity. The results of this study contribute to our understanding how genes with very short upstream intergenic regions are regulated and how these regions can serve as a source for MAMP-responsive cis-sequences for synthetic promoter design. PMID- 26833486 TI - Anti-Ri antibody associated small cell lung carcinoma. AB - BACKGROUND: Anti-neuronal antibody Anti-Ri may be positive in patients with paraneoplastic syndrome associated with certain cancer subtypes. Anti-Ri positivity has been associated with breast, gynaecological and small cell lung cancers. CASE REPORT: A 69 year-old female presented with a sudden decline in cognition requiring hospital admission. She had an extensive medical history including a significant smoking history and bipolar affective disorder for which she was prescribed lithium. Her cognitive decline was initially attributed to diabetes insipidus secondary to lithium therapy. She made a slow but gradual recovery with treatment. Additional investigations revealed positive Anti-Ri antibody. An occult malignancy screen identified enlarged aorto-pulmonary lymph nodes of indeterminate significance. Following discussion at the regional cardiothoracic multidisciplinary team meeting, three monthly surveillance scans were performed. At month 6 an increase in thoracic adenopathy was seen however endobronchial ultrasound guided biopsy failed to identify malignant cells. Further progression with new supraclavicular adenopathy was seen on repeat imaging 6 months later. A fine need aspirate of an enlarged supraclavicular lymph node was diagnostic for small cell lung cancer, staged as TxN3M0 on positron emission tomography. The patient went on to receive sequential chemo-radiotherapy with a truncated course of carboplatin and etoposide and 50 Gy/25 fractions of thoracic radiotherapy. DISCUSSION: This case suggests that a positive Anti-Ri antibody may predate the development of clinical or radiological evidence of malignancy. If Anti-Ri positivity is identified, strong consideration should be given to screening for malignancy and regular surveillance. This approach may lead to earlier diagnosis and a better outcome for these patients. PMID- 26833487 TI - Get the GIST? An overview of gastrointestinal stromal tumours. AB - GISTs are the most common mesenchymal neoplasms of the gastrointestinal tract. The last 20 years have been revolutionary in the understanding of these tumours and began with the discovery of c-KIT, a proto oncogene that when mutated forms the molecular basis for the growth and development of these malignancies. Surgery was previously considered to be the only treatment modality in both local and advanced disease, however, the introduction of immunotherapy agents such as tyrosine kinase inhibitors has had profound effects on how we now approach and manage these tumours. These novel agents have significantly reduced the frequency of disease recurrence and dramatically improved survival, and serve as a model for the study of targeted therapies in other solid tumors. We present a review of gastrointestinal stromal tumours and consider the current evidence based detection and management of these unique tumors. PMID- 26833488 TI - The temporal fluctuations and characteristics of psychiatric inpatient admissions in Ireland: data from the HRB's National Psychiatric In-Patient Reporting System. AB - This paper examines trends in psychiatric inpatient admissions from the 1960s to 2014 and uses data from the National Psychiatric Inpatient Reporting System (NPIRS) to review these trends. In the 1960s the Department of Health began an annual system of reporting on the activities in Irish psychiatric units and hospitals on foot of the recommendations of the Commission of Inquiry on Mental Illness. The National Psychiatric Inpatient Reporting System (NPIRS) was established shortly thereafter and this paper discusses the data from this database contained in these annual activity reports over the last 50 years. PMID- 26833489 TI - Numerical Simulation of Focused Shock Shear Waves in Soft Solids and a Two Dimensional Nonlinear Homogeneous Model of the Brain. AB - Shear waves that propagate in soft solids, such as the brain, are strongly nonlinear and can develop into shock waves in less than one wavelength. We hypothesize that these shear shock waves could be responsible for certain types of traumatic brain injuries (TBI) and that the spherical geometry of the skull bone could focus shear waves deep in the brain, generating diffuse axonal injuries. Theoretical models and numerical methods that describe nonlinear polarized shear waves in soft solids such as the brain are presented. They include the cubic nonlinearities that are characteristic of soft solids and the specific types of nonclassical attenuation and dispersion observed in soft tissues and the brain. The numerical methods are validated with analytical solutions, where possible, and with self-similar scaling laws where no known solutions exist. Initial conditions based on a human head X-ray microtomography (CT) were used to simulate focused shear shock waves in the brain. Three regimes are investigated with shock wave formation distances of 2.54 m, 0.018 m, and 0.0064 m. We demonstrate that under realistic loading scenarios, with nonlinear properties consistent with measurements in the brain, and when the shock wave propagation distance and focal distance coincide, nonlinear propagation can easily overcome attenuation to generate shear shocks deep inside the brain. Due to these effects, the accelerations in the focal are larger by a factor of 15 compared to acceleration at the skull surface. These results suggest that shock wave focusing could be responsible for diffuse axonal injuries. PMID- 26833490 TI - Dental amalgam exposure can elevate urinary mercury concentrations in children. AB - OBJECTIVES: Owing to its cost-effectiveness and operative convenience, dental amalgam remains in use as a restorative material for tooth caries in children in many countries. The aim of this study was to evaluate the relationship between dental amalgam exposure and urinary mercury (U-Hg) concentrations in children. METHODS: In this longitudinal study, 463, 367 and 348 children, 8-11 years of age, were evaluated at baseline, and at the first and second follow-up visits, respectively. The interval between each survey was 6 months. For the oral examination and urine sample, the amalgam-filled tooth surface (TS), and U-Hg and creatinine concentrations of participants were determined, and the cumulative amalgam-filled TS and cumulative creatinine-adjusted U-Hg were calculated. To assess potential covariates, socio-demographic factors, oral health behaviour and dietary factors were surveyed by questionnaire. Data were analysed by the t-test, correlation analysis and mixed-model analysis. The statistical analyses were performed using SPSS 18.0. RESULTS: Children with more than one amalgam-filled TS exhibited significantly higher creatinine-adjusted U-Hg concentrations than those without, in all three survey periods (P < 0.001). The results for the current and cumulative amalgam-filled TS significantly correlated with those for the current and cumulative creatinine-adjusted U-Hg concentration, respectively, in all surveys (P < 0.001). In the repeated-measures mixed model analysis, current and cumulative amalgam-filled TS was significantly related to current and cumulative creatinine-adjusted U-Hg concentration, respectively (P < 0.001). CONCLUSIONS: Amalgam-filled TS was significantly correlated with U-Hg concentrations in children. Therefore, dental amalgam exposure can affect the systemic mercury concentration in children. PMID- 26833492 TI - Lessons from Queer Bioethics: A Response to Timothy F. Murphy. AB - 'Bioethics still has important work to do in helping to secure status equality for LGBT people' writes Timothy F. Murphy in a recent Bioethics editorial. The focus of his piece, however, is much narrower than human rights, medical care for LGBT people, or ending the HIV/AIDS pandemic. Rather, he is primarily concerned with sexuality and gender identity, and the medical intersections thereof (i.e. DSM diagnosis; access to SrS or ARTs). It is the objective of this response to provide an alternate account of bioethics from a Queer perspective. I will situate Queer bioethics within Queer studies, and offer three 'lessons' that bioethics can derive from this perspective. These are not definitive rules for Queer bioethics, since it is a field which fundamentally opposes categorizations, favoring pastiche over principles. These lessons are exploratory examples, which both complement and contradict LGBT bioethics. My latter two lessons - on environmental bioethics and disability - overlap with some of Murphy's concerns, as well as other conceptions of LGBT bioethics. However, the first lesson takes an antithetical stance to Murphy's primary focus by resisting all forms of heteroconformity and disavowing reproduction as consonant with Queer objectives and theory. The first lesson, which doubles as a primer in Queer theory, does heavy philosophical lifting for the remainder of the essay. This response to Timothy F. Murphy, whose work is certainly a legacy in bioethics, reveals the multiplicity of discourses in LGBT/Queer studies, many of which are advantageous even essential - to other disciplines like bioethics. PMID- 26833491 TI - Intrarenal alterations of the angiotensin-converting enzyme type 2/angiotensin 1 7 complex of the renin-angiotensin system do not alter the course of malignant hypertension in Cyp1a1-Ren-2 transgenic rats. AB - The role of the intrarenal renin-angiotensin system (RAS) in the pathophysiology of malignant hypertension is not fully understood. Accumulating evidence indicates that the recently discovered vasodilator axis of the RAS, angiotensin converting enzyme (ACE) type 2 (ACE2)/angiotensin 1-7 (ANG 1-7), constitutes an endogenous system counterbalancing the hypertensiogenic axis, ACE/angiotensin II (ANG II)/AT1 receptor. This study aimed to evaluate the role of the intrarenal vasodilator RAS axis in the pathophysiology of ANG II-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. ANG II-dependent malignant hypertension was induced by 13 days' dietary administration of indole-3-carbinol (I3C), a natural xenobiotic that activates the mouse renin gene in Cyp1a1-Ren-2 transgenic rats. It was hypothesized that pharmacologically-induced inhibition of the ACE2/ANG 1-7 complex should aggravate, and activation of this axis should attenuate, the course of ANG II-dependent malignant hypertension. Blood pressure (BP) was monitored by radiotelemetry. ACE2 inhibitor (DX 600, 0.2 MUg/day) and ACE2 activator (DIZE, 1 mg/day) were administrated via osmotic minipumps. Even though ACE2 inhibitor significantly decreased and ACE2 activator increased intrarenal ANG 1-7 concentrations, the course of BP, as well as of albuminuria, cardiac hypertrophy and renal glomerular damage, were not altered. It was shown that intrarenal alterations in the ACE2/ANG 1-7 complex did not significantly modify the course of malignant hypertension in I3C-induced Cyp1a1-Ren-2 transgenic rats. Thus, in our experimental setting alterations of this intrarenal vasodilator complex of the RAS do not significantly modify the form of malignant hypertension that clearly depends on the inappropriately increased activity of the ACE/ANG II/AT1 receptor axis. PMID- 26833493 TI - Chest physiotherapy for acute bronchiolitis in paediatric patients between 0 and 24 months old. AB - BACKGROUND: This Cochrane review was first published in 2005 and updated in 2007, 2012 and now 2015. Acute bronchiolitis is the leading cause of medical emergencies during winter in children younger than two years of age. Chest physiotherapy is sometimes used to assist infants in the clearance of secretions in order to decrease ventilatory effort. OBJECTIVES: To determine the efficacy of chest physiotherapy in infants aged less than 24 months old with acute bronchiolitis. A secondary objective was to determine the efficacy of different techniques of chest physiotherapy (for example, vibration and percussion and passive forced exhalation). SEARCH METHODS: We searched CENTRAL (2015, Issue 9) (accessed 8 July 2015), MEDLINE (1966 to July 2015), MEDLINE in-process and other non-indexed citations (July 2015), EMBASE (1990 to July 2015), CINAHL (1982 to July 2015), LILACS (1985 to July 2015), Web of Science (1985 to July 2015) and Pedro (1929 to July 2015). SELECTION CRITERIA: Randomised controlled trials (RCTs) in which chest physiotherapy was compared against no intervention or against another type of physiotherapy in bronchiolitis patients younger than 24 months of age. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data. Primary outcomes were change in the severity status of bronchiolitis and time to recovery. Secondary outcomes were respiratory parameters, duration of oxygen supplementation, length of hospital stay, use of bronchodilators and steroids, adverse events and parents' impression of physiotherapy benefit. No pooling of data was possible. MAIN RESULTS: We included 12 RCTs (1249 participants), three more than the previous Cochrane review, comparing physiotherapy with no intervention. Five trials (246 participants) evaluated conventional techniques (vibration and percussion plus postural drainage), and seven trials (1003 participants) evaluated passive flow-oriented expiratory techniques: slow passive expiratory techniques in four trials, and forced passive expiratory techniques in three trials.Conventional techniques failed to show a benefit in the primary outcome of change in severity status of bronchiolitis measured by means of clinical scores (five trials, 241 participants analysed). Safety of conventional techniques has been studied only anecdotally, with one case of atelectasis, the collapse or closure of the lung resulting in reduced or absent gas exchange, reported in the control arm of one trial.Slow passive expiratory techniques failed to show a benefit in the primary outcomes of severity status of bronchiolitis and in time to recovery (low quality of evidence). Three trials analysing 286 participants measured severity of bronchiolitis through clinical scores, with no significant differences between groups in any of these trials, conducted in patients with moderate and severe disease. Only one trial observed a transient significant small improvement in the Wang clinical score immediately after the intervention in patients with moderate severity of disease. There is very low quality evidence that slow passive expiratory techniques seem to be safe, as two studies (256 participants) reported that no adverse effects were observed.Forced passive expiratory techniques failed to show an effect on severity of bronchiolitis in terms of time to recovery (two trials, 509 participants) and time to clinical stability (one trial, 99 participants analysed). This evidence is of high quality and corresponds to patients with severe bronchiolitis. Furthermore, there is also high quality evidence that these techniques are related to an increased risk of transient respiratory destabilisation (risk ratio (RR) 10.2, 95% confidence interval (CI) 1.3 to 78.8, one trial) and vomiting during the procedure (RR 5.4, 95% CI 1.6 to 18.4, one trial). Results are inconclusive for bradycardia with desaturation (RR 1.0, 95% CI 0.2 to 5.0, one trial) and bradycardia without desaturation (RR 3.6, 95% CI 0.7 to 16.9, one trial), due to the limited precision of estimators. However, in mild to moderate bronchiolitis patients, forced expiration combined with conventional techniques produced an immediate relief of disease severity (one trial, 13 participants). AUTHORS' CONCLUSIONS: None of the chest physiotherapy techniques analysed in this review (conventional, slow passive expiratory techniques or forced expiratory techniques) have demonstrated a reduction in the severity of disease. For these reasons, these techniques cannot be used as standard clinical practice for hospitalised patients with severe bronchiolitis. There is high quality evidence that forced expiratory techniques in severe patients do not improve their health status and can lead to severe adverse events. Slow passive expiratory techniques provide an immediate and transient relief in moderate patients without impact on duration. Future studies should test the potential effect of slow passive expiratory techniques in mild to moderate non-hospitalised patients and patients who are respiratory syncytial virus (RSV) positive. Also, they could explore the combination of chest physiotherapy with salbutamol or hypertonic saline. PMID- 26833495 TI - Abstracts of the 15th Annual Congress of the French Speaking Society of Transplantation, Lille, France, 1-4 December 2015. PMID- 26833494 TI - Incorporating Functional Genomic Information in Genetic Association Studies Using an Empirical Bayes Approach. AB - There is a large amount of functional genetic data available, which can be used to inform fine-mapping association studies (in diseases with well-characterised disease pathways). Single nucleotide polymorphism (SNP) prioritization via Bayes factors is attractive because prior information can inform the effect size or the prior probability of causal association. This approach requires the specification of the effect size. If the information needed to estimate a priori the probability density for the effect sizes for causal SNPs in a genomic region isn't consistent or isn't available, then specifying a prior variance for the effect sizes is challenging. We propose both an empirical method to estimate this prior variance, and a coherent approach to using SNP-level functional data, to inform the prior probability of causal association. Through simulation we show that when ranking SNPs by our empirical Bayes factor in a fine-mapping study, the causal SNP rank is generally as high or higher than the rank using Bayes factors with other plausible values of the prior variance. Importantly, we also show that assigning SNP-specific prior probabilities of association based on expert prior functional knowledge of the disease mechanism can lead to improved causal SNPs ranks compared to ranking with identical prior probabilities of association. We demonstrate the use of our methods by applying the methods to the fine mapping of the CASP8 region of chromosome 2 using genotype data from the Collaborative Oncological Gene-Environment Study (COGS) Consortium. The data we analysed included approximately 46,000 breast cancer case and 43,000 healthy control samples. PMID- 26833497 TI - Synthesis of Triarylpyridines in Thiopeptide Antibiotics by Using a C-H Arylation/Ring-Transformation Strategy. AB - We have described a C-H arylation/ring-transformation strategy for the synthesis of triarylpyridines, which form the core structure of thiopeptide antibiotics. This synthetic method readily gave 2,3,6-triarylpyridines in a regioselective manner by a two-phase approach: C-H arylation (a nickel-catalyzed decarbonylative Suzuki-Miyaura cross-coupling and decarbonylative C-H coupling for the synthesis of 2,4-diaryloxazoles) and ring transformation ([4+2] cycloaddition of 2,4 diaryloxazoles with (hetero)arylacrylic acids). To showcase these methods, we have accomplished the formal synthesis of thiopeptide antibiotics GE2270 s and amythiamicins. PMID- 26833496 TI - Should I stay or should I go? Initiation of joint travel in mother-infant dyads of two chimpanzee communities in the wild. AB - It is well established that great apes communicate via intentionally produced, elaborate and flexible gestural means. Yet relatively little is known about the most fundamental steps into this communicative endeavour-communicative exchanges of mother-infant dyads and gestural acquisition; perhaps because the majority of studies concerned captive groups and single communities in the wild only. Here, we report the first systematic, quantitative comparison of communicative interactions of mother-infant dyads in two communities of wild chimpanzees by focusing on a single communicative function: initiation of carries for joint travel. Over 156 days of observation, we recorded 442 actions, 599 cases of intentional gesture production, 51 multi-modal combinations and 80 vocalisations in the Kanyawara community, Kibale National Park, Uganda, and the Tai South community, Tai National Park, Cote d'Ivoire. Our results showed that (1) mothers and infants differed concerning the signal frequency and modality employed to initiate joint travel, (2) concordance rates of mothers' gestural production were relatively low within but also between communities, (3) infant communicative development is characterised by a shift from mainly vocal to gestural means, and (4) chimpanzee mothers adjusted their signals to the communicative level of their infants. Since neither genetic channelling nor ontogenetic ritualization explains our results satisfactorily, we propose a revised theory of gestural acquisition, social negotiation, in which gestures are the output of social shaping, shared understanding and mutual construction in real time by both interactants. PMID- 26833498 TI - Intrapericardial Amiodarone for the Prevention of Postoperative Atrial Fibrillation. AB - Despite probably being the most effective prophylactic drug for postoperative atrial fibrillation (POAF), amiodarone is reserved as a second-line agent because of its potential systemic side effects. Herein, we review the available experimental and clinical trials examining the effectiveness of intrapericardial (IPC) amiodarone administration in preventing POAF which, if confirmed by future studies, can have a significant impact on cardiac surgery practice. PMID- 26833499 TI - Construction of a 2D Graphene-Like MoS2/C3N4 Heterojunction with Enhanced Visible Light Photocatalytic Activity and Photoelectrochemical Activity. AB - A novel graphene-like MoS2 /C3N4 (GL-MoS2/C3N4) composite photocatalyst has been synthesized by a facile ethylene glycol (EG)-assisted solvothermal method. The structure and morphology of this GL-MoS2/C3N4 photocatalyst have been investigated by a wide range of characterization methods. The results showed that GL-MoS2 was uniformly distributed on the surface of GL-C3N4 forming a heterostructure. The obtained composite exhibited strong absorbing ability in the ultraviolet (UV) and visible regions. When irradiated with visible light, the composite photocatalyst showed high activity superior to those of the respective individual components GL-MoS2 and GL-C3N4 in the degradation of methyl orange. The enhanced photocatalytic activity of the composite may be attributed to the efficient separation of electron-hole pairs as a result of the matching band potentials between GL-MoS2 and GL-C3N4. Furthermore, a photocatalytic mechanism for the composite material has been proposed, and the photocatalytic reaction kinetics has been measured. Moreover, GL-MoS2/C3N4 could serve as a novel sensor for trace amounts of Cu(2+) since it exhibited good selectivity for Cu(2+) detection in water. PMID- 26833500 TI - We Are Family: Specifying the Unique Contribution of Abuse and Neglect of Siblings on the Prevalence, Severity, and Chronicity of Maltreatment in the Household. AB - Prior research typically focuses on a single child ("index" victim) when measuring child abuse and neglect (CAN) using Child Protective Services (CPS) records. However, excluding siblings has the potential to underestimate estimates of the prevalence, severity, and chronicity of CAN in the household, which includes all children in the family. CPS maltreatment records were searched in 2005 for 366 "index" victims who were surveyed for 5 consecutive years (from 1998 to 2002) for the Mobile Youth Survey (MYS) as well as other siblings in the household. The estimate of prevalence of CAN in the household increased by 10% when sibling(s) in the household were included in the CPS search. In addition, prevalence of sexual abuse in the household increased by 38% when siblings were included in the broader search of CPS records. More importantly, including sibling victims of CAN uncovered incidents of maltreatment that occurred before the birth of the targeted MYS "index" victim. In short, the inclusion of abuse and neglect of siblings is a straightforward and intuitive way to improve estimates of abuse and neglect in the household. More importantly, the age of onset of CAN of sibling victims provides a wider window of opportunity to identify at-risk families for targeted interventions and may represent a critical stepping stone toward the primary prevention of CAN in the household. PMID- 26833506 TI - Migratory waves rocking the boat? PMID- 26833507 TI - Clinical leadership - are clinicians up for it? PMID- 26833505 TI - Group II Intron-Mediated Trans-Splicing in the Gene-Rich Mitochondrial Genome of an Enigmatic Eukaryote, Diphylleia rotans. AB - Although mitochondria have evolved from a single endosymbiotic event, present day mitochondria of diverse eukaryotes display a great range of genome structures, content and features. Group I and group II introns are two features that are distributed broadly but patchily in mitochondrial genomes across branches of the tree of eukaryotes. While group I intron-mediated trans-splicing has been reported from some lineages distantly related to each other, findings of group II intron-mediated trans-splicing has been restricted to members of the Chloroplastida. In this study, we found the mitochondrial genome of the unicellular eukaryote Diphylleia rotans possesses currently the second largest gene repertoire. On the basis of a probable phylogenetic position of Diphylleia, which is located within Amorphea, current mosaic gene distribution in Amorphea must invoke parallel gene losses from mitochondrial genomes during evolution. Most notably, although the cytochrome c oxidase subunit (cox) 1 gene was split into four pieces which located at a distance to each other, we confirmed that a single mature mRNA that covered the entire coding region could be generated by group II intron-mediated trans-splicing. This is the first example of group II intron-mediated trans-splicing outside Chloroplastida. Similar trans-splicing mechanisms likely work for bipartitely split cox2 and nad3 genes to generate single mature mRNAs. We finally discuss origin and evolution of this type of trans-splicing in D. rotans as well as in eukaryotes. PMID- 26833508 TI - Excellence in cost-effective inpatient specialist palliative care in the NHS - a new model. AB - There is little in the literature describing hospital specialist palliative care units (PCUs) within the NHS. This paper describes how specialist PCUs can be set up within and be entirely funded by the NHS, and outlines some of the challenges and successes of the units. Having PCUs within hospitals has offered patients increased choice over their place of care and death; perhaps not surprisingly leading to a reduced death rate in the acute hospital. However, since the opening of the PCUs there has also been an increased home death rate. The PCUs are well received by patients, families and other staff within the hospital. We believe they offer a model for excellence in cost-effective inpatient specialist palliative care within the NHS. PMID- 26833509 TI - Practise what you preach: health behaviours and stress among non-consultant hospital doctors. AB - High rates of psychological distress, depression and suicide have been reported among doctors. Furthermore, many doctors do not access healthcare by conventional means. This study aimed to increase understanding regarding non-consultant hospital doctors' (NCHDs') response to stress and barriers to accessing supports, and identify possible solutions. Medical manpower departments in 58 hospitals distributed a 25-item questionnaire to 4,074 NCHDs; we received 707 responses (response rate, 17.4%). 60% of NCHDs were unable to take time off work when unwell; 'letting teammates down' (90.8%) and 'difficulty covering call' (85.9%) were the leading reasons. 'Being too busy' (85%), 'self-prescription' (66.6%) and 'self-management' (53.1%) were ranked highest in deterring NCHDs from visiting a general practitioner (GP). 22.9% of NCHDs would not attend a GP with anxiety or depression until they began to feel hopeless, helpless or suicidal. 12.2% would not seek help at all. 55% of respondents (n = 330) had to move away from partners or dependants due to work, negatively affecting the social supports of 82.9%. Possible practical solutions were explored. NCHDS are a vulnerable population and have a particularly challenging lifestyle. Key recommendations include improved GP and counselling access for NCHDs, and addressing the culture of self-treatment and poor health behaviours through undergraduate and postgraduate education. PMID- 26833510 TI - Embedding comprehensive geriatric assessment in the emergency assessment unit: the impact of the COPE zone. AB - We introduced a geographically embedded frailty unit, the comprehensive older person's evaluation 'COPE' zone within our emergency assessment unit (EAU). We collated data for all medical patients over 75 years admitted non-electively for one month before and after this service change. Significantly more patients were seen by a geriatrician on the EAU earlier in their admission in 2014 (33.4 vs 19.3%, p<0.001; 11 vs 20 h, p<0.001). More patients had documented comprehensive geriatric assessment and discussion in a geriatrician multidisciplinary team meeting (relative risk (RR) 3.3, 95% confidence interval (CI) 2.35-4.73, p<0.001; RR 3.6, 95% CI 2.26-5.57, p<0.001, respectively). More patients with markers of frailty were discharged directly from EAU (42.2 vs 29.0%, p = 0.006) without increasing readmissions. Mean length of stay was reduced (9.5 vs 6.8 days, p = 0.02). The introduction of the COPE zone has improved service delivery at the point of access for older people admitted to hospital. PMID- 26833511 TI - Heart failure - what the general physician needs to know. AB - The British Society of Heart Failure (BSH) meetings highlight the latest advancements within the field of heart failure (HF) and provide education for training and revalidation for cardiologists and general physicians. This article reviews take-home messages from the 7th BSH HF revalidation and training meeting. It emphasises what every physician needs to know about the latest acute HF guidelines, diagnostics in HF, management strategies (including pharmacotherapeutics and device therapy), and when to consider referring to a transplant centre for mechanical circulatory support or transplantation. It describes the practical challenges faced and provides clinicians with a framework to assist with service development and commissioning of resources to deliver optimal, integrated services that meet the ever-advancing needs of our HF communities. PMID- 26833512 TI - Sarcoidosis of the cardio-pulmonary systems. AB - Sarcoidosis is a multi-system disease with a wide range of phenotypes. Pulmonary involvement is the most frequently identified target for sarcoidosis and is responsible for the majority of deaths. Cardiac sarcoid is less commonly identified, may be occult, is significantly influenced by race, and can portend an unpredictable and sometimes fatal outcome. Sarcoidosis remains an enigmatic disease spectrum of unknown aetiology, frequently difficult to diagnose and with a variable disease course. This article summarises current views on the diagnosis and management of cardiopulmonary involvement. PMID- 26833513 TI - Therapeutic advances in idiopathic pulmonary fibrosis. AB - Idiopathic pulmonary fibrosis (IPF) is characterised by progressive accumulation of scar tissue in the lung and is associated with a median life expectancy of 2-4 years. Until recently, treatment options were limited, focusing on ineffective anti-inflammatory therapy, palliation, transplant or trial recruitment. Significant recent advances in the field have led to two novel anti-fibrotic agents, pirfenidone and nintedanib, which have been shown to significantly slow disease progression in IPF. This article outlines the approach to management of IPF, the role of specialist centres and specialist interstitial lung disease multidisciplinary review, and explores both the trial evidence and practical considerations in the use of these anti-fibrotic agents. PMID- 26833514 TI - Hypertension - state of the art 2015. AB - A conference organised in conjunction with the British Hypertension Society at the Royal College of Physicians (London) assembled an expert panel to present recent advances in the understanding and management of hypertension - the leading reversible risk factor for global morbidity and mortality. Despite recognised therapeutic approaches, less than half of patients on treatment for hypertension achieve blood pressure control to international guideline-based targets. This failure may, in part, be due to uncertainty into optimum treatment strategies, and the PATHWAY studies reporting later this year will hopefully address some outstanding questions relating to the standardised ABCD approach to drug selection. Targeting degradation of natriuretic peptides by LCZ696 (a combination of valsartan and a neutral endopeptidase inhibitor) has demonstrated potential as a novel therapeutic option, with mortality benefits in heart failure beyond that solely attributable to its blood pressure lowering ability. However, critical to any therapeutic strategy is patient involvement, and it is clear that the delivery of patient-centric treatment options is vital to ensure adherence with medication and to facilitate healthier lifestyle decisions. PMID- 26833515 TI - Advances in pathogenesis and treatment of systemic sclerosis. AB - Systemic sclerosis is the most severe disease within the scleroderma spectrum and is a major medical challenge with high mortality and morbidity. There have been advances in understanding of pathogenesis that reflect the interplay between immune-inflammatory processes and vasculopathy and fibrosis. It can be regarded as a disease of connective tissue repair and this leads to organ-based complications. However the aetiology and triggering events remain to be elucidated. Treatment is available for many aspects of the disease although the available therapies are not curative and some complications remain very challenging, especially non-lethal manifestations such as fatigue, calcinosis and anorectal dysfunction. Immunosuppression is now established as a beneficial approach but balancing risk and benefit is vital, especially for powerful approaches such as autologous stem cell transplantation. PMID- 26833517 TI - An IVF pregnancy, a neck lump and shortness of breath. PMID- 26833516 TI - Dermatology: a specialty in crisis. PMID- 26833518 TI - Clinical and scientific letters: On-going lessons in fluid prescription: assessment of adherence to weight-based intravenous fluid prescribing in medical inpatients. PMID- 26833519 TI - Non-melanoma skin cancer. AB - Non-melanoma skin cancer (NMSC) comprises basal cell carcinoma (BCC) and squamous cell carcinoma, together with a host of rare tumours. NMSC is the commonest malignancy among Caucasians and its incidence continues to rise annually. Exposure to UV radiation initiates approximately 90% of NMSC, causing malignant transformation of keratinocytes and suppression of the inflammatory response. Risk factors include sun exposure and immunosuppression. There are several subtypes of BCC, although histological overlap is common. Surgery has traditionally been regarded as the 'gold-standard' treatment, offering excellent cure rates and cosmetic results. Other treatment modalities include physical destruction (radiotherapy, curettage and cautery, and cryotherapy), chemical destruction (photodynamic therapy and topical 5-flurouracil) and immunomodulatory therapy (topical imiquimod). The recent development of novel hedgehog pathway inhibitors for high-risk BCC (including oral vismodegib and sonidegib) may represent a paradigm shift towards medical management of NMSC. PMID- 26833520 TI - Atopic eczema. AB - Atopic eczema is an itchy inflammatory skin disease with a chronic relapsing remitting course; it has increased in prevalence in recent decades and now affects up to 25% of school-aged children in the developed world and up to 10% of adults. Recent advances in understanding the aetiology of eczema have focused interest on skin barrier dysfunction as a common precursor and pathological feature. In addition, genetically determined skin barrier dysfunction (associated with mutations in the gene encoding filaggrin) is known to predispose to multiple systemic atopic diseases. First-line treatments for atopic eczema focus on maintaining and repairing the skin barrier (emollients) and reducing inflammation (topical steroids); allergen and irritant avoidance are also important to achieve disease control. Second and third-line treatments include topical calcineurin inhibitors, ultraviolet light and systemic immunosuppressant therapies of which only ciclosporin is licenced for the treatment of atopic eczema in adults. Novel biological therapies are in phase II-III clinical trials. PMID- 26833521 TI - Hidradenitis suppurativa: an update. AB - Hidradenitis suppurativa (HS) is a chronic, painful skin disease characterised by recurrent inflammatory lesions in flexural locations such as the axillae, groins and perineum. The papules, nodules and abscesses may discharge blood-stained pus which, combined with pain, results in marked quality-of-life reduction. Sinus tracts and scarring may also result. Onset of HS is typically in the second to fourth decades and it affects about 1% of young European adults. There are links with smoking and obesity and an autosomal dominant pattern of inheritance is reported by one-third of patients. Medical management escalates from topical antimicrobials to oral tetracyclines, a combination of clindamycin and rifampicin typically given for 10 weeks, oral disease modifiers, and anti-tumour necrosis factor-alpha therapies. Excision of individual lesions has high recurrence rates which can be minimised by wider excisions, at the expense of longer healing times. Treatment of pain is a relatively neglected aspect of therapy. PMID- 26833522 TI - Alopecia in general medicine. AB - Appreciation of different types of hair loss (alopecia) that may be encountered in hospital medicine is important to ensure accurate diagnosis and management, identify underlying medical conditions or treatments that may present with increased hair loss, recognise autoimmune alopecias and their associations, and understand the significant psychological impact of hair loss on an individual. This article discusses common causes of hair loss, as well as those conditions that may be associated with systemic disease, relevant to a general physician. PMID- 26833523 TI - Severe adverse drug reactions. AB - Severe cutaneous adverse reactions (SCARs) can present in a multitude of ways including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalised exanthematous pustulosis. While the prognosis and therapy for these conditions may vary, it is crucial that the culprit drug is identified and withheld early as this can influence patient outcome. Mainstay of management is by supportive therapy. In all SCARs, long-term sequelae which may not be apparent initially can be debilitating and cause lasting impact on the quality of life of survivors. PMID- 26833524 TI - CME Dermatology (100625): self-assessment questionnaire. PMID- 26833525 TI - Lesson of the month 1: Artery of Percheron occlusion - an -uncommon cause of coma in a middle-aged man. AB - Bilateral paramedian thalamic infarction resulting from artery of Percheron occlusion presents with a distinct clinical syndrome comprising impaired consciousness, often with vertical gaze palsy and memory impairment. This uncommon anatomical variant arises as a single artery supplying both paramedian thalami. Early recognition can be challenging in the obtunded patient, where the differential diagnosis is broad. The acute physician should consider this diagnosis in a patient presenting with unexplained coma so that emergent treatments such as thrombolysis can be employed. Early imaging with computerised tomography can often be normal; therefore the use of magnetic resonance imaging is essential in confirming the diagnosis. PMID- 26833526 TI - Lesson of the month 2: Cauda equina in Cushing's syndrome. AB - We present the case of a 34-year old woman who initially presented with obesity and back pain. She was eventually diagnosed with Cushing's syndrome secondary to an adrenocortical carcinoma that had metastasised to her spine, causing cauda equina compression. The delays in reaching the correct diagnosis caused significant morbidity and exemplify the pitfalls of premature closing, a common cognitive error in diagnostic reasoning. PMID- 26833527 TI - Bilateral gigantic earlobe keloids. PMID- 26833528 TI - The independent validation of the Foundation Programme application process: a closer look. PMID- 26833529 TI - Systematic review on the prevalence of lack of capacity in medical and psychiatric settings. PMID- 26833530 TI - Response. PMID- 26833531 TI - Drug therapy in older people with heart failure. PMID- 26833532 TI - Response. PMID- 26833533 TI - A cough that doesn't fit the mould. PMID- 26833534 TI - Response. PMID- 26833535 TI - Variation and Trends in Anaphylaxis Care in United States Children's Hospitals. AB - OBJECTIVES: We sought to determine the extent of variation in treatment of children with anaphylaxis. METHODS: We identified children 1 month to 18 years of age presenting with a primary diagnosis of anaphylaxis to one of the 35 pediatric hospitals included in the Pediatric Health Information System between January 1, 2009, and September 30, 2013. We evaluated the variation in use of beta2 agonists, glucocorticoids, histamine-1 (H1) antagonists, histamine-2 (H2) antagonists, inhaled epinephrine, intravenous fluids, and oxygen. We assessed whether variation exists in the rates of hospitalization and 3-day emergency department (ED) revisits and whether a temporal trend exists in the ED visit rate for anaphylaxis. RESULTS: Among 10,351 children with anaphylaxis, the hospital level median use of common anaphylaxis therapies varied for beta2 agonists (22%, interquartile range [IQR] = 16%-26%), glucocorticoids (71%, IQR = 65%-76%), H1 blockers (60%, IQR = 57%-65%), H2 blockers (53%, IQR = 36%-64%), inhaled epinephrine (2.2%, IQR = 1.3%-3.5%), intravenous fluids (26%, IQR = 13%-41%), and oxygen (2.6%, IQR = 0.8%-4.1%). Hospitalization rates ranged from 12% to 95%, with a median rate of 41%. Anaphylaxis diagnoses rose from 5.7 to 11.7 patients per 10,000 ED visits between 2009 and 2013 (p < 0.001 for trend). CONCLUSIONS: There is substantial variability in the use of common therapies and hospitalization rates for children cared for in U.S. children's hospitals. Additionally, ED visits for children with anaphylaxis are increasing at U.S. children's hospitals. These findings highlight the need for research defining optimal care for anaphylaxis. PMID- 26833536 TI - Evaluation of the application of the European guidelines for the diagnosis and clinical care of amyotrophic lateral sclerosis (ALS) patients in six French ALS centres. AB - BACKGROUND AND PURPOSE: Our objective was to evaluate the extent to which the 2005 recommendations of the European Federation of Neurological Sciences (EFNS) on the multidisciplinary management of amyotrophic lateral sclerosis (ALS) are followed in clinical practice. METHODS: This was a multicentre observational study involving six French ALS referral centres receiving prevalent and incident cases. Recommendations were translated into ad hoc questions referring to key aspects of management, and their application was evaluated by a clinical research assistant who independently examined the medical charts (MCs). When necessary, an independent board-certified neurologist answered the questions based on examination of the MC and interview of the caring neurologist. Questions regarding diagnosis and communication were put to patients in a self-administered questionnaire. RESULTS: In all, 376 patients [176 incident, 200 prevalent cases; median age at diagnosis 62.8 years (interquartile range 55.7-72.3); sex ratio 1.37; 27.3% bulbar onset] were included. All the topics covered in the recommendations were evaluated: diagnostic delay (e.g. mean 13.6 months, associated with age and onset); breaking the news (e.g. criteria for communication quality were satisfactory in more than 90%); multidisciplinary and sustained support (e.g. clinic visits were scheduled every 2-3 months in 90%). Also considered were whether riluzole had been offered, symptom management, genetic testing, ventilation, communication defects, enteral nutrition, palliative and end-of-life care. Characteristics associated with poor compliance with some guidelines (schedule of visits, delayed riluzole initiation) were also identified. CONCLUSION: This is the first evaluation of the application of the EFNS recommendations for the management of ALS in a nationwide sample. The results allow us to highlight areas for improvement. PMID- 26833537 TI - Quick and stable parallel puncture of hepatic tumors using a double-barreled needle direction system for ultrasound-guided bipolar radiofrequency ablation. AB - AIM: In bipolar radiofrequency ablation (RFA) therapy, insertion of multiple needles at appropriate points on a target is difficult. The aim of our study was to evaluate a simplified method for multi-electrode insertion using a newly developed double-barreled needle guidance system for percutaneous RFA of hepatic tumors. METHODS: RFA using two bipolar electrodes was performed in 15 consecutive patients (nine men, six women; mean age, 72.0 +/- 8.2 years) with a solitary small (<=3 cm) hepatic tumor. The first five nodules were treated using the conventional puncture method with the standard attachment, then 10 nodules were ablated using the parallel puncture method with the double-barreled attachment. The times required for double-needle placement and the shapes of the ablated areas were compared between the two puncture methods. RESULTS: The parallel puncture method required a shorter time for double-needle placement than the conventional method (12 s [range, 8-24] vs 96 s [range, 50-240]; P = 0.0003), and allowed continuous observation of the tip of all needles and the size of the ablated area as it increased until completion of the ablation. The method also provided a stable ellipsoidal ablated area. The median height, width and thickness were 30 mm (range, 22-34), 30 mm (range, 21-33) and 20 mm (range, 7 25), respectively, using 20-mm electrodes, and 34 mm (range, 32-41), 36 mm (range, 35-38) and 24 mm (range, 23-24), respectively, using 30-mm electrodes. CONCLUSION: The parallel puncture method may be a feasible procedure for multi needle RFA therapy. PMID- 26833538 TI - Longer procedural times are independently associated with symptomatic intracranial hemorrhage in patients with large vessel occlusion stroke undergoing thrombectomy. AB - BACKGROUND: Time to reperfusion is an essential factor in determination of outcomes in acute ischemic stroke (AIS). OBJECTIVE: To establish the effect of the procedural time on the clinical outcomes of patients with AIS. METHODS: Data from all consecutive patients who underwent mechanical thrombectomy between September 2010 and July 2012 were analysed retrospectively. The variable of interest was procedural time (defined as time from groin puncture to final recanalization time). Outcome measures included the rates of symptomatic intracranial hemorrhage (sICH, defined as any parenchymal hematoma-eg, PH-1/PH 2), final infarct volume, 90-day mortality, and independent functional outcomes (modified Rankin Scale 0-2) at 90 days. RESULTS: The cohort included 242 patients with a mean age of 65.5+/-14.2 and median baseline National Institutes of Health Stroke Scale score 20. 51% of the patients were female. The mean procedure time was significantly shorter in patients with a good outcome (86.7 vs 73.1 min, respectively, p=0.0228). Patients with SICH had significantly higher mean procedure time than patients without SICH (79.67 vs 104.5 min, respectively; p=0.0319), which remained significant when controlling for the previous factors (OR=0.974, 95% CI 0.957 to 0.991). No correlation was found between the volume of infarction and the procedure time (r=0.10996, p=0.0984). No association was seen between procedure time and 90-day mortality (77.8 vs 88.2 min in survivals vs deaths, respectively; p=0.0958). CONCLUSIONS: Our data support an association between the risk of SICH and a longer procedure time, but no association between procedural times and the final infarction volume or long-term functional outcomes was found. PMID- 26833539 TI - Quantitative assessment of device-clot interaction for stent retriever thrombectomy. AB - PURPOSE: Rapid revascularization in emergent large vessel occlusion with endovascular embolectomy has proven clinical benefit. We sought to measure device clot interaction as a potential mechanism for efficient embolectomy. METHODS: Two different radiopaque clot models were injected to create a middle cerebral artery occlusion in a patient-specific vascular phantom. A radiopaque stent retriever was deployed within the clot by unsheathing the device or a combination of unsheathing followed by pushing the device (n=8/group). High-resolution cone beam CT was performed immediately after device deployment and repeated after 5 min. An image processing pipeline was created to quantitatively evaluate the volume of clot that integrates with the stent, termed the clot integration factor (CIF). RESULTS: The CIF was significantly different for the two deployment variations when the device engaged the hard clot (p=0.041), but not the soft clot (p=0.764). In the hard clot, CIF increased significantly between post-deployment and final imaging datasets when using the pushing technique (p=0.019), but not when using the unsheathing technique (p=0.067). When we investigated the effect of time on CIF in the different clot models disregarding the technique, the CIF was significantly increased in the final dataset relative to the post-deployment dataset in both clot models (p=0.004-0.007). CONCLUSIONS: This study demonstrates in an in vitro system the benefit of pushing the Trevo stent during device delivery in hard clot to enhance integration. Regardless of delivery technique, clot-device integration increased in both clot models by waiting 5 min. PMID- 26833540 TI - Antimicrobial resistance, integron carriage, and gyrA and gyrB mutations in Pseudomonas aeruginosa isolated from dogs with otitis externa and pyoderma in Brazil. AB - BACKGROUND: Pseudomonas aeruginosa is associated with otitis and pyoderma in dogs and is frequently resistant to several antimicrobial drugs. Resistance genes can be carried by integrons with quinolone resistance mainly due to mutations in DNA topoisomerases II and IV. OBJECTIVE: To evaluate the antimicrobial susceptibility, integron carriage, and gyrA and gyrB mutations in P. aeruginosa isolates from canine otitis and pyoderma. ANIMALS: One hundred and four P. aeruginosa strains isolated from dogs with otitis externa (n = 93) and pyoderma (n = 11). METHODS: Antimicrobial susceptibility against 16 antibacterial agents was evaluated through agar diffusion tests. Integron carriage, class and gyrA and gyrB mutations were analysed by PCR, restriction fragment length polymorphism (RFLP)-PCR and genetic sequencing assays. RESULTS: Isolates were mostly resistant to enrofloxacin (72.2%) and ticarcillin (59.7%). Lower resistance to ciprofloxacin (7.7%), tobramycin (3.8%) and polymixin B (0.0%) was detected. Ten (9.6%) multidrug-resistant (MDR) strains were detected. Eight (7.7%) strains carried class 1 integrons and this was associated with MDR (three isolates, P <= 0.05). Five of the integron-carrying strains exhibited aminoglycoside resistance genes. Mutations of gyrA and gyrB were observed in 10 isolates, seven of them resistant to all fluoroquinolones tested. CONCLUSIONS AND CLINICAL IMPORTANCE: Enrofloxacin and ticarcilin resistance was widespread in P. aeruginosa isolated from dogs in Brazil. Pseudomonas aeruginosa carrying integrons may present a significant challenge for treatment. PMID- 26833541 TI - Determination and Identification of a Specific Marker Compound for Discriminating Shrub Chaste Tree Fruit from Agnus Castus Fruit Based on LC/MS Metabolic Analysis. AB - Shrub Chaste Tree Fruit (SCTF) is defined as the fruits of Vitex rotundifolia L. f. and V. trifolia L. and has been used as a component of some traditional Japanese medicines (Kampo formulations). Agnus Castus Fruit (ACF) is defined as the dried ripe fruits of V. agnus-castus L.; it is used in traditional European medicines, but is becoming popular in Japan as both an over-the-counter drug and as an ingredient in health foods for treating premenstrual syndrome (PMS). To ensure the efficacy and safety of both SCTF and ACF products, it is important to precisely authenticate their botanical origins and to clearly distinguish between SCTF and ACF. Therefore, we tried to identify SCTF-specific marker compounds based on LC/MS metabolic analysis. The multivariate analysis of LC/MS data from SCTF and ACF samples furnished candidate marker compounds of SCTF. An SCTF specific marker was isolated from SCTF crude drugs and identified as 3-O-trans feruloyl tormentic acid on the basis of spectroscopic data from NMR and MS. Since avoiding contamination from closely related species is a significant requirement for pharmaceuticals of natural origin, this information will be valuable for the quality control of both SCTF and ACF products from the viewpoint of regulatory science. PMID- 26833542 TI - Enzymatic hydrolysis of biomass from wood. AB - Current research and development in cellulosic ethanol production has been focused mainly on agricultural residues and dedicated energy crops such as corn stover and switchgrass; however, woody biomass remains a very important feedstock for ethanol production. The precise composition of hemicellulose in the wood is strongly dependent on the plant species, therefore different types of enzymes are needed based on hemicellulose complexity and type of pretreatment. In general, hardwood species have much lower recalcitrance to enzymes than softwood. For hardwood, xylanases, beta-xylosidases and xyloglucanases are the main hemicellulases involved in degradation of the hemicellulose backbone, while for softwood the effect of mannanases and beta-mannosidases is more relevant. Furthermore, there are different key accessory enzymes involved in removing the hemicellulosic fraction and increasing accessibility of cellulases to the cellulose fibres improving the hydrolysis process. A diversity of enzymatic cocktails has been tested using from low to high densities of biomass (2-20% total solids) and a broad range of results has been obtained. The performance of recently developed commercial cocktails on hardwoods and softwoods will enable a further step for the commercialization of fuel ethanol from wood. PMID- 26833543 TI - Modelling the current and potential future distributions of the sunn pest Eurygaster integriceps (Hemiptera: Scutelleridae) using CLIMEX. AB - BACKGROUND: The sunn pest, Eurygaster integriceps (Hemiptera: Scutelleridae), is an economically significant pest throughout Western Asia and Eastern Europe. This study was conducted to examine the possible risk posed by the influence of climate change on its spread. CLIMEX software was used to model its current global distribution. Future invasion potential was investigated using two global climate models (GCMs), CSIRO-Mk3.0 (CS) and MIROC-H (MR), under A1B and A2 emission scenarios for 2030, 2070 and 2100. RESULTS: Dry to temperate climatic areas favour sunn pests. The potential global range for E. integriceps is expected to extend further polewards between latitudes 60 degrees N and 70 degrees N. Northern Europe and Canada will be at risk of sunn pest invasion as cold stress boundaries recede under the emission scenarios of these models. However, current highly suitable areas, such as South Africa and central Australia, will contract where precipitation is projected to decrease substantially with increased heat stress. CONCLUSION: Estimating the sunn pest's potential geographic distribution and detecting its climatic limits can provide useful information for management strategies and allow biosecurity authorities to plan ahead and reduce the expected harmful economic consequences by identifying the new areas for pest invasion. (c) 2016 Society of Chemical Industry. PMID- 26833545 TI - A Rhizavidin Monomer with Nearly Multimeric Avidin-Like Binding Stability Against Biotin Conjugates. AB - Developing a monomeric form of an avidin-like protein with highly stable biotin binding properties has been a major challenge in biotin-avidin linking technology. Here we report a monomeric avidin-like protein-enhanced monoavidin with off-rates almost comparable to those of multimeric avidin proteins against various biotin conjugates. Enhanced monoavidin (eMA) was developed from naturally dimeric rhizavidin by optimally maintaining protein rigidity during monomerization and additionally shielding the bound biotin by diverse engineering of the surface residues. eMA allowed the monovalent and nonperturbing labeling of head-group-biotinylated lipids in bilayer membranes. In addition, we fabricated an unprecedented 24-meric avidin probe by fusing eMA to a multimeric cage protein. The 24-meric avidin and eMA were utilized to demonstrate how artificial clustering of cell-surface proteins greatly enhances the internalization rates of assembled proteins on live cells. PMID- 26833546 TI - Identification of Hox genes and rearrangements within the single homeobox (Hox) cluster (192.8 kb) of the cyclopoid copepod (Paracyclopina nana). AB - We report the first identification of the entire complement of the eight typical homeobox (hox) genes (lab, pb, Dfd, scr, antp, ubx, Abd-A, and Abd-B) and the ftz gene in a 192.8 kb region in the cyclopoid copepod Paracyclopina nana. A Hox3 gene ortholog was not present in the P. nana hox gene cluster, while the P. nana Dfd gene was transcribed in the opposite direction to the Daphnia pulex Dfd gene, but in the same direction as the Dfd genes of the fruit fly Drosophila melanogaster and red flour beetle Tribolium castaneum. The location of the lab and pb genes was switched in the P. nana hox cluster, while the order of the remaining hox genes was generally conserved with those of other arthropods. J. Exp. Zool. (Mol. Dev. Evol.) 9999B:XX-XX, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26833544 TI - Association between the change in body mass index from early adulthood to midlife and subsequent type 2 diabetes mellitus. AB - OBJECTIVE: To clarify the quantitative relationship of body mass index (BMI) change from early adulthood to midlife with presence of type 2 diabetes mellitus (T2DM) after midlife. METHODS: This study included 120,666 middle-aged and elderly, whose retrospectively self-reported body weight at 20 and 40 years and measured height were available. BMI at 20 and 40 years and BMI change in between were defined as early-adulthood BMI, midlife BMI, and early-adulthood BMI change. RESULTS: The odds ratio (OR) for T2DM associated with an 1-unit increment of early-adulthood or midlife BMI was 1.08 (95% confidence interval (CI), 1.07-1.08) and 1.09 (95% CI, 1.09-1.10) respectively. In the cross-tabulation of both early adulthood BMI and BMI change, the prevalence of T2DM increased across both variables. Compared with participants with normal early-adulthood weight and BMI increase/decrease <=1, the OR (95% CI) for T2DM of participants with early adulthood overweight/obesity and BMI increase >=4 kg/m(2) was 3.49 (3.05-4.00). For participants with early-adulthood underweight and BMI increase/decrease <= 1, the OR (95% CI) was 0.85 (0.75-0.97). Subgroup analysis according to sex and age showed similar trends. CONCLUSIONS: Early-adulthood BMI may influence T2DM prevalence after midlife independent of current BMI. T2DM prevalence after midlife was positively associated with early-adulthood weight gain and inversely related to early-adulthood weight loss, while early-adulthood weight loss could not completely negate the adverse effect of early-adulthood overweight/obesity on diabetes. PMID- 26833547 TI - Impact of soil heat on reassembly of bacterial communities in the rhizosphere microbiome and plant disease suppression. AB - The rhizosphere microbiome offers a range of ecosystem services to the plant, including nutrient acquisition and tolerance to (a)biotic stress. Here, analysing the data by Mendes et al. (2011), we show that short heat disturbances (50 or 80 degrees C, 1 h) of a soil suppressive to the root pathogenic fungus Rhizoctonia solani caused significant increase in alpha diversity of the rhizobacterial community and led to partial or complete loss of disease protection. A reassembly model is proposed where bacterial families that are heat tolerant and have high growth rates significantly increase in relative abundance after heat disturbance, while temperature-sensitive and slow-growing bacteria have a disadvantage. The results also pointed to a potential role of slow-growing, heat-tolerant bacterial families from Actinobacteria and Acidobacteria phyla in plant disease protection. In conclusion, short heat disturbance of soil results in rearrangement of rhizobacterial communities and this is correlated with changes in the ecosystem service disease suppression. PMID- 26833548 TI - Biodegradable Self-Assembled Nanoparticles of Galactose-Containing Amphiphilic Triblock Copolymers for Targeted Delivery of Paclitaxel to HepG2 Cells. AB - Biodegradable self-assembled polymeric nanoparticles (NPs) composed of poly(6-O methacryloyl-D-galactopyranose)-b-poly(L-lactide)-b-poly(6-O-methacryloyl-D galactopyranose) (PMAGP-b-PLA-b-PMAGP) are prepared as carriers for the hydrophobic anticancer drug paclitaxel (PTX), to achieve target delivery to hepatoma cells. PTX can be encapsulated by the NPs with various molar ratios of L lactide (LA) and 6-O-methacryloyl-D-galactopyranose (MAGP) during the process of self-assembly, and the resulting NPs exhibit high drug loading efficacy and substantial stability in aqueous solution. The size, size distribution, and morphology of the NPs are characterized using a Zetasizer Nano ZS and transmission electron microscopy. The hemolysis assay and cell cytotoxicity assay indicate that the polymeric NPs are biocompatible and non-toxic. The cellular uptake assay demonstrates that the galactose-containing NPs can be selectively recognized and subsequently accumulate in HepG2 cells. All of these results demonstrate that galactose-containing polymeric NPs are potential carriers for hepatoma-targeted drug delivery and liver cancer therapy in clinical medicine. PMID- 26833549 TI - Canine mammary carcinomas: influence of histological grade, vascular invasion, proliferation, microvessel density and VEGFR2 expression on lymph node status and survival time. AB - Spontaneous invasive non-inflammatory canine mammary carcinomas (CMC) and their regional lymph nodes (LN) were analysed (n = 136). Histological grade (HG) and vascular invasion (VI) in the tumours and lymph node status were recorded. Proliferation index (PI), microvessel density (MVD) and vascular endothelial growth factor receptor 2 (VEGFR2) expression were estimated using anti proliferating cell nuclear antigen (PCNA), anti-von Willebrand factor and anti Flk-1, respectively. Eighteen months follow-up was performed (34 bitches). Tumours of different grades showed differences regarding PI, Flk-1/integrated optical density (Flk-1/IOD) and MVD. Every feature showed significant association with LN status through bivariate analyses. From multivariate analyses, VI and Flk 1/IOD were selected to predict LN status. Data revealed that the probability of a CMC-bearing bitch to remain alive at 1, 4, 5 and 14-18 months was 0.91, 0.87, 0.81 and 0.77, respectively. Besides LN status, VI was the only feature positively correlated with survival time, although a trend to shorter survival of animal patients bearing high expressing VEGFR2 CMC was noted. PMID- 26833550 TI - Draf III mucosal graft technique: long-term results. AB - BACKGROUND: The Draf III procedure is an effective endoscopic approach to the treatment of frontal sinus disorders, but has a significant restenosis rate. The objective of the current study is to assess long-term success of the Draf III mucosal grafting technique. METHODS: Patients undergoing Draf III with mucosal grafting technique were prospectively enrolled. Demographics, indication for surgery, anterior-posterior (AP) diameter of frontal ostium, and complications were recorded. Failure was defined a priori as closure >=50% of the intraoperative AP diameter at last clinical follow-up. RESULTS: Ninety-six patients requiring Draf III with mucosal grafting were enrolled, 67 of which (average age 54 years; range, 15-84 years) had at least 1 year of follow-up (average 34 months; range, 12-85 months) and were included in the analysis. Reasons for the procedure included chronic rhinosinusitis with frontal ostium stenosis (n = 37), tumor (n = 26), and cerebrospinal fluid leak (n = 4). Average preoperative Lund-Mackay score was 13.9 +/- 7.8. Average intraoperative AP diameter was 11.0 +/- 1.9 mm. The procedure was highly effective with 97% (65/67) of patients maintaining a patent frontal sinus ostium (>50% intraoperative AP diameter) for the duration of follow-up (average postoperative diameter 9.9 +/- 2.2 mm). However, the 2 Draf III failures remained patent, did not need further intervention, and were considered clinically successful. Three patients required reoperation for reasons unrelated to closure of the Draf III. CONCLUSION: Common causes of failure following Draf III procedures include osteoneogenesis and stenosis. This study provides long-term data demonstrating excellent outcomes using the mucosal grafting technique. PMID- 26833551 TI - Skeletal muscle dysfunction in the db/db mouse model of type 2 diabetes. AB - INTRODUCTION: In this study we examined the mechanisms of motor dysfunction in type 2 diabetes. METHODS: Contractile force was measured in isolated nerve-muscle preparations of db/db mice using various protocols for electrical stimulation. Sarcoplasmic reticulum Ca(2+) adenosine triphosphatase protein (SERCA) was quantified by comparing Ca(2+) -dependent and non-specific phosphorylation. RESULTS: Compared with controls, the muscle-nerve preparations of db/db mice displayed muscle atrophy, reduced axonal excitability, and force deficit when stimulated via the nerve. Muscle relaxation after contraction was slowed, and SERCA content was reduced. In contrast, the sensitivity of the neuromuscular junction to tubocurarine and muscle fiber excitability were not affected. CONCLUSIONS: The force deficit in db/db muscles was caused by atrophy and failure of neuromuscular signal transmission related to motor nerve axonal dysfunction. The slowed relaxation rate generally observed in diabetic muscles can, to a large extent, be explained by decreased SERCA pump content. Muscle Nerve 54: 460-468, 2016. PMID- 26833552 TI - Clinical Neuropathology Views - 2/2016: Digital networking in European neuropathology: An initiative to facilitate truly interactive consultations. AB - Digital technology is progressively changing our vision of the practice of neuropathology. There are a number of facts that support the introduction of digital neuropathology. With the development of wholeslide imaging (WSI) systems the difficulties involved in implementing a neuropathology network have been solved. A relevant difficulty has been image standardization, but an open digital image communication protocol defined by the Digital Imaging and Communications in Medicine (DICOM) standard is already a reality. The neuropathology network should be established in Europe because it is the expected geographic context for relationships among European neuropathologists. There are several limitations in the implementation of a digital neuropathology consultancy network such as financial support, operational costs, legal issues, and technical assistance of clients. All of these items have been considered and should be solved before implementing the proposal. Finally, the authors conclude that a European digital neuropathology network should be created for patients' benefit. PMID- 26833553 TI - Should Deceased Donation be Morally Preferred in Uterine Transplantation Trials? AB - In recent years much research has been undertaken regarding the feasibility of the human uterine transplant (UTx) as a treatment for absolute uterine factor infertility (AUFI). Should it reach clinical application this procedure would allow such individuals what is often a much-desired opportunity to become not only social mothers (via adoption or traditional surrogacy arrangements), or genetic and social mothers (through gestational surrogacy) but mothers in a social, genetic and gestational sense. Like many experimental transplantation procedures such as face, hand, corneal and larynx transplants, UTx as a therapeutic option falls firmly into the camp of the quality of life (QOL) transplant, undertaken with the aim, not to save a life, but to enrich one. However, unlike most of these novel procedures - where one would be unlikely to find a willing living donor or an ethics committee that would sanction such a donation - the organs to be transplanted in UTx are potentially available from both living and deceased donors. In this article, in the light of the recent nine case research trial in Sweden which used uteri obtained from living donors, and the assertions on the part of a number of other research teams currently preparing trials that they will only be using deceased donors, I explore the question of whether, in the case of UTx, there exist compelling moral reasons to prefer the use of deceased donors despite the benefits that may be associated with the use of organs obtained from the living. PMID- 26833554 TI - Effect of esomeprazole on the oral absorption of dasatinib in a patient with Philadelphia-positive acute lymphoblastic leukemia. PMID- 26833555 TI - Simultaneous Assessment of Myocardial Perfusion, Wall Motion, and Deformation during Myocardial Contrast Echocardiography: A Feasibility Study. AB - AIMS: Ultrasound contrast agents may be used for the assessment of regional wall motion and myocardial perfusion, but are generally considered not suitable for deformation analysis. The aim of our study was to assess the feasibility of deformation imaging on contrast-enhanced images using a novel methodology. METHODS AND RESULTS: We prospectively enrolled 40 patients who underwent stress echocardiography with continuous intravenous infusion of SonoVue for the assessment of myocardial perfusion imaging with flash replenishment technique. We compared longitudinal strain (Lepsilon) values, assessed with a vendor independent software (2D CPA), on 68 resting contrast-enhanced and 68 resting noncontrast recordings. Strain analysis on contrast recordings was evaluated in the first cardiac cycles after the flash. Tracking of contrast images was deemed feasible in all subjects and in all views. Contrast administration improved image quality and increased the number of segments used for deformation analysis. Lepsilon of noncontrast and contrast-enhanced images were statistically different (-18.8 +/- 4.5% and -22.8 +/- 5.4%, respectively; P < 0.001), but their correlation was good (ICC 0.65, 95%CI 0.42-0.78). Patients with resting wall motion abnormalities showed lower Lepsilon values on contrast recordings (-18.6 +/- 6.0% vs. -24.2 +/- 5.5%, respectively; P < 0.01). Intra-operator and inter operator reproducibility was good for both noncontrast and contrast images with no statistical differences. CONCLUSIONS: Our study shows that deformation analysis on postflash contrast-enhanced images is feasible and reproducible. Therefore, it would be possible to perform a simultaneous evaluation of wall motion abnormalities, volumes, ejection fraction, perfusion defects, and cardiac deformation on the same contrast recording. PMID- 26833556 TI - Local Field Modulation Induced Three-Order Upconversion Enhancement: Combining Surface Plasmon Effect and Photonic Crystal Effect. AB - A 2D surface plasmon photonic crystal (SPPC) is achieved by implanting gold nanorods onto the periodic surface apertures of the poly(methyl methacrylate) (PMMA) opal photonic crystals. On the surface of the SPPC, the overall upconversion luminescence intensity of NaYF4 :Yb(3+) , Er(3+) under 980 nm excitation is improved more than 10(3) fold. The device is easily shifted to a transparent flexible substrate, applied to flexible displays. PMID- 26833557 TI - Platinum-Catalyzed Friedel-Crafts-Type C-H Coupling-Allylic Amination Cascade to Synthesize 3,4-Fused Tricyclic Indoles. AB - A novel platinum-catalyzed cascade cyclization reaction was developed by intramolecular Friedel-Crafts-type C-H coupling of aniline derivatives with a propargyl carbonate unit-allylic amination sequence. Treatment of various propargyl carbonates tethered to meta-aniline derivatives with a Pt(dba)3/DPEphos catalyst system afforded the corresponding 3,4-fused tricyclic 3-alkylidene indolines in 42-99% yield, which were transformed into 3,4-fused indole derivatives by reaction with trifluoroacetic acid. The reaction products exhibited antiproliferative activities against cancer cells, but not normal cells, revealing the potential usefulness of this reaction for medicinal chemistry. PMID- 26833558 TI - Structural analysis of the active site architecture of the VapC toxin from Shigella flexneri. AB - The VapC toxin from the Shigella flexneri 2a virulence plasmid pMYSH6000 belongs to the PIN domain protein family, which is characterized by a conserved fold with low amino acid sequence conservation. The toxin is a bona fide Mg(2+) -dependent ribonuclease and has been shown to target initiator tRNA(fMet) in vivo. Here, we present crystal structures of active site catalytic triad mutants D7A, D7N, and D98N of the VapC toxin in absence of antitoxin. In all structures, as well as in solution, VapC forms a dimer. In the D98N structure, a Hepes molecule occupies both active sites of the dimer and comparison with the structure of RNase H bound to a DNA/RNA hybrid suggests that the Hepes molecule mimics the position of an RNA nucleotide in the VapC active site. Proteins 2016; 84:892-899. (c) 2016 Wiley Periodicals, Inc. PMID- 26833559 TI - Recent Development of Durable and Self-Healing Surfaces with Special Wettability. AB - Artificial special wetting surfaces have drawn much interest due to their important applications in many fields. Nevertheless, tremendous challenges still remain for the fabrication of wetting surfaces with durable and self-healing properties. Here, recent progress of durable, self-healing wetting surfaces is highlighted by discussing the fabrications of several typical wetting surfaces including superhydrophobic surfaces, superamphiphobic surfaces, underwater superoleophobic surfaces, and high hydrophilic antifouling surfaces based on expertise and related research experience. To conclude, some perspectives on the future research and development of these special wetting surfaces are presented. PMID- 26833560 TI - Non-Thermal Plasma in Contact with Water: The Origin of Species. AB - Non-thermal atmospheric pressure plasma has attracted considerable attention in recent years due to its potential for biomedical applications. Determining the mechanism of the formation of reactive species in liquid treated with plasma is thus of paramount importance for both fundamental and applied research. In this work, the origin of reactive species in plasma-treated aqueous solutions was investigated by using spin-trapping, hydrogen and oxygen isotopic labelling and electron paramagnetic resonance (EPR) spectroscopy. The species originating from molecules in the liquid phase and those introduced with the feed gas were differentiated by EPR and 1 H NMR analysis of liquid samples. The effects of water vapour and oxygen admixtures in the feed gas were investigated. All the reactive species detected in the liquid samples were shown to be formed largely in the plasma gas phase. It is suggested that hydrogen peroxide (determined by UV/Vis analysis) is formed primarily in the plasma tube, whereas the radical species ?OOH, ?OH and ?H are proposed to originate from the region between the plasma nozzle and the liquid sample. PMID- 26833561 TI - Performance of rapid diagnostic tests for the detection of antibodies to hepatitis C virus in whole blood collected on dried blood spots. AB - Rapid diagnostic tests (RDTs) represent an attractive alternative to enzyme immunoassays. A total of 207 individuals, including 68 HCV-seronegative subjects, 10 patients with resolved infection and 129 patients with chronic HCV infection, were studied. The specificity of RDT detection of anti-HCV antibodies in whole blood was 100% with the four RDTs tested: OraQuick((r)) HCV Rapid Antibody Test, First Response HCV Card Test, ASSURE HCV Rapid Test and MultiSure HCV Antibody Assay. Their diagnostic sensitivity varied between 98.6% and 100%. RDT detection of anti-HCV antibody in whole blood collected on dried blood spots appears to be a promising new tool for broadscale screening of HCV infection in high- to medium risk populations. PMID- 26833562 TI - Risk stratification of allograft failure secondary to hepatitis C recurrence after liver transplantation. AB - AIM: Hepatitis C virus (HCV) recurrence after liver transplantation decreases survival rates. Improved understanding of the multiple factors influencing HCV recurrence could aid decision-making for donor-recipient pairing and maximize transplant outcomes. The aim of this study was to create a model based on pretransplant variables to stratify patients at risk of HCV-related allograft failure. METHODS: This retrospective study enrolled 154 liver transplant recipients with HCV at Cleveland Clinic. RESULTS: Among the study population, 54 recipients (35.1%) experienced HCV recurrence, histologically defined as moderate to severe hepatitis and/or bridging fibrosis to cirrhosis. The multivariate analysis found donor age (>=60 years, P < 0.002), donor body mass index (>=30 kg/m2 , P < 0.05), African American recipient (P < 0.01) and genotype 1 (P < 0.02) as risk factors for HCV-related allograft failure. When these four factors were scored as a combined index (no factor [n = 15], one factor [n = 76], two factors [n = 43] and three or more factors [n = 20]), the HCV recurrence-free survival showed good stratification according to the scores: 93.3% with no factor, 79.3% with one factor, 52.0% with two factors and 24.4% with three or more factors at 3 years after transplant (P < 0.0001). Moreover, this risk index also identified the patient group at high risk of HCV recurrence after acute rejection. CONCLUSION: While the introduction of direct-acting antiviral agents has been changing the paradigm of HCV treatment, the natural history of recipients with HCV as shown in this study would help estimate the risk of HCV related allograft failure in those who do not tolerate such new treatment. PMID- 26833563 TI - Epidermal jasmonate perception is sufficient for all aspects of jasmonate mediated male fertility in Arabidopsis. AB - Jasmonate (JA) signaling is essential for several environmental responses and reproductive development in many plant species. In Arabidopsis thaliana, the most obvious phenotype of JA biosynthetic and perception mutants is profound sporophytic male sterility characterized by failure of stamen filament elongation, severe delay of anther dehiscence and pollen inviability. The site of action of JA in the context of reproductive development has been discussed, but the ideas have not been tested experimentally. To this end we used targeted expression of a COI1-YFP transgene in the coi1-1 mutant background. As COI1 is an essential component of the JA co-receptor complex, the null coi1-1 mutant is male sterile due to lack of JA perception. We show that expression of COI1-YFP in the epidermis of the stamen filament and anther in coi1 mutant plants is sufficient to rescue filament elongation, anther dehiscence and pollen viability. In contrast, filament expression alone or expression in the tapetum do not restore dehiscence and pollen viability. These results demonstrate that epidermal JA perception is sufficient for anther function and pollen viability, and suggest the presence of a JA-dependent non-autonomous signal produced in the anther epidermis to synchronize both anther dehiscence and pollen maturation. PMID- 26833564 TI - p300/beta-Catenin Interactions Regulate Adult Progenitor Cell Differentiation Downstream of WNT5a/Protein Kinase C (PKC). AB - Maintenance of stem/progenitor cell-progeny relationships is required for tissue homeostasis during normal turnover and repair. Wnt signaling is implicated in both maintenance and differentiation of adult stem/progenitor cells, yet how this pathway serves these dichotomous roles remains enigmatic. We previously proposed a model suggesting that specific interaction of beta-catenin with either of the homologous Kat3 co-activators, p300 or CREB-binding protein, differentially regulates maintenance versus differentiation of embryonic stem cells. Limited knowledge of endogenous mechanisms driving differential beta-catenin/co-activator interactions and their role in adult somatic stem/progenitor cell maintenance versus differentiation led us to explore this process in defined models of adult progenitor cell differentiation. We focused primarily on alveolar epithelial type II (AT2) cells, progenitors of distal lung epithelium, and identified a novel axis whereby WNT5a/protein kinase C (PKC) signaling regulates specific beta catenin/co-activator interactions to promote adult progenitor cell differentiation. p300/beta-catenin but not CBP/beta-catenin interaction increases as AT2 cells differentiate to a type I (AT1) cell-like phenotype. Additionally, p300 transcriptionally activates AT1 cell-specific gene Aqp-5. IQ-1, a specific inhibitor of p300/beta-catenin interaction, prevents differentiation of not only primary AT2 cells, but also tracheal epithelial cells, and C2C12 myoblasts. p300 phosphorylation at Ser-89 enhances p300/beta-catenin interaction, concurrent with alveolar epithelial cell differentiation. WNT5a, a traditionally non-canonical WNT ligand regulates Ser-89 phosphorylation and p300/beta-catenin interactions in a PKC-dependent manner, likely involving PKCzeta. These studies identify a novel intersection of canonical and non-canonical Wnt signaling in adult progenitor cell differentiation that has important implications for targeting beta-catenin to modulate adult progenitor cell behavior in disease. PMID- 26833565 TI - Cholesterol Analogs with Degradation-resistant Alkyl Side Chains Are Effective Mycobacterium tuberculosis Growth Inhibitors. AB - Cholest-4-en-3-one, whether added exogenously or generated intracellularly from cholesterol, inhibits the growth ofMycobacterium tuberculosiswhen CYP125A1 and CYP142A1, the cytochrome P450 enzymes that initiate degradation of the sterol side chain, are disabled. Here we demonstrate that a 16-hydroxy derivative of cholesterol, which was previously reported to inhibit growth ofM. tuberculosis, acts by preventing the oxidation of the sterol side chain even in the presence of the relevant cytochrome P450 enzymes. The finding that (25R)-cholest-5-en 3beta,16beta,26-triol (1) (and its 3-keto metabolite) inhibit growth suggests that cholesterol analogs with non-degradable side chains represent a novel class of anti-mycobacterial agents. In accord with this, two cholesterol analogs with truncated, fluorinated side chains have been synthesized and shown to similarly block the growth in culture ofM. tuberculosis. PMID- 26833566 TI - Structural Basis for Sialoglycan Binding by the Streptococcus sanguinis SrpA Adhesin. AB - Streptococcus sanguinisis a leading cause of infective endocarditis, a life threatening infection of the cardiovascular system. An important interaction in the pathogenesis of infective endocarditis is attachment of the organisms to host platelets.S. sanguinisexpresses a serine-rich repeat adhesin, SrpA, similar in sequence to platelet-binding adhesins associated with increased virulence in this disease. In this study, we determined the first crystal structure of the putative binding region of SrpA (SrpABR) both unliganded and in complex with a synthetic disaccharide ligand at 1.8 and 2.0 A resolution, respectively. We identified a conserved Thr-Arg motif that orients the sialic acid moiety and is required for binding to platelet monolayers. Furthermore, we propose that sequence insertions in closely related family members contribute to the modulation of structural and functional properties, including the quaternary structure, the tertiary structure, and the ligand-binding site. PMID- 26833567 TI - Multiple Domains of GlcNAc-1-phosphotransferase Mediate Recognition of Lysosomal Enzymes. AB - The Golgi enzyme UDP-GlcNAc:lysosomal enzymeN-acetylglucosamine-1 phosphotransferase (GlcNAc-1-phosphotransferase), an alpha2beta2gamma2hexamer, mediates the initial step in the addition of the mannose 6-phosphate targeting signal on newly synthesized lysosomal enzymes. This tag serves to direct the lysosomal enzymes to lysosomes. A key property of GlcNAc-1-phosphotransferase is its unique ability to distinguish the 60 or so lysosomal enzymes from the numerous non-lysosomal glycoproteins with identical Asn-linked glycans. In this study, we demonstrate that the two Notch repeat modules and the DNA methyltransferase-associated protein interaction domain of the alpha subunit are key components of this recognition process. Importantly, different combinations of these domains are involved in binding to individual lysosomal enzymes. This study also identifies the gamma-binding site on the alpha subunit and demonstrates that in the majority of instances the mannose 6-phosphate receptor homology domain of the gamma subunit is required for optimal phosphorylation. These findings serve to explain how GlcNAc-1-phosphotransferase recognizes a large number of proteins that lack a common structural motif. PMID- 26833568 TI - Dihydroxynaphthalene-based mimicry of fungal melanogenesis for multifunctional coatings. AB - Material-independent adhesive action derived from polycatechol structures has been intensively studied due to its high applicability in surface engineering. Here, we for the first time demonstrate that a dihydroxynaphthalene-based fungal melanin mimetic, which exhibit a catechol-free structure, can act as a coating agent for material-independent surface modifications on the nanoscale. This mimetic was made by using laccase to catalyse the oxidative polymerization of specifically 2,7-dihydroxynaphthalene. Analyses of the product of this reaction, using Fourier transform infrared-attenuated total reflectance and X-ray photoelectron spectroscopy, bactericidal action, charge-dependent sorption behaviour, phenol content, Zeta potential measurements and free radical scavenging activity, yielded results consistent with it containing hydroxyphenyl groups. Moreover, nuclear magnetic resonance analyses of the product revealed that C-O coupling and C-C coupling were the main mechanisms for its synthesis, thus clearly excluding a catechol structure in the polymerization. This product, termed poly(2,7-DHN), was successfully deposited onto a wide variety of solid surfaces, including metals, polymeric materials, ceramics, biosurfaces and mineral complexes. The melanin-like polymerization could be used to co-immobilize other organic molecules, forming functional surfaces. In addition, the hydroxyphenyl group contained in the coated poly(2,7-DHN) induced secondary metal chelation/reduction and adhesion with proteins, suggesting the potential of this poly(2,7-DHN) layer to serve as a platform material for a variety of surface engineering applications. Moreover, the novel physicochemical properties of the poly(2,7-DHN) illuminate its potential applications as bactericidal, radical scavenging and pollutant-sorbing agents. PMID- 26833569 TI - Automated analysis of sleep control via a single neuron active at sleep onset in C. elegans. AB - Longitudinal analyses are crucial for understanding long-term processes such as development and behavioral rhythms. For a complete understanding of such processes, both organism-level observations as well as single-cell observations are necessary. Sleep is an example for a long-term process that is under developmental control. This behavioral state is induced by conserved sleep-active neurons, but little is known about how sleep neurons control the physiology of an animal systemically. In the nematode C. elegans, sleep induction crucially requires the single RIS interneuron to actively induce a developmentally regulated sleep behavior. Here, we used RIS-induced sleep as an example of how longitudinal analyses can be automated. We developed methods to analyze both behavior and neural activity in larva across the sleep-wake cycle. To image behavior, we used an improved DIC contrast to extract the head and detect the nose. To image neural activity, we used GCaMP3 expression in a small number of neurons including RIS combined with a neuron discrimination algorithm. Thus, we present a comprehensive platform for automatically analyzing behavior and neural activity in C. elegans exemplified by using RIS-induced sleep during C. elegans development. PMID- 26833570 TI - Association between a school-based intervention and adiposity outcomes in adolescents: The Italian "EAT" project. AB - OBJECTIVE: To evaluate whether a school-based multicomponent educational program could improve adiposity measures in middle-school adolescents. METHODS: A non randomized controlled pilot study was conducted in six state middle schools (487 adolescents, 11-15 years) in townships in an urban area around Milan, three schools (n = 262 adolescents) being assigned to the intervention group and three schools (n = 225 adolescents) to the control group. The two-school-year intervention included changes in the school environment (alternative healthy vending machines, educational posters) and individual reinforcement tools (school lessons, textbook, text messages, pedometers, re-usable water bottles). The main outcome measure was change in BMI z-score. The secondary outcomes were changes in waist-to-height ratio (WHtR) and behavioral habits. RESULTS: The intervention was associated with a significant difference in BMI z-score (-0.18 +/- 0.03, P<0.01) and in WHtR (-0.04 +/- 0.002, P < 0.001), after controlling for baseline covariates. Subgroup analysis showed the maximum association between the intervention and the difference in BMI z-score for girls with overweight/obesity. Physical activity increased and consumption of sugar-sweetened beverages and high energy snacks decreased in adolescents after the intervention. CONCLUSIONS: A school-based multicomponent intervention conducted at both environmental and individual levels may be effective for reducing adiposity measures mainly in adolescents with overweight/obesity. PMID- 26833571 TI - Experimental and Theoretical Evidence for an Agostic Interaction in a Gold(III) Complex. AB - The first agostic interaction in a gold complex is described. The presence of a bonding C-H???Au interaction in a cationic "tricoordinate" gold(III) complex was suggested by DFT calculations and was subsequently confirmed by NMR spectroscopy at low temperature. The agostic interaction was analyzed computationally using NBO and QTAIM analyses (NBO=natural bond orbital; QTAIM=quantum theory of atoms in molecules). PMID- 26833572 TI - Shape change in mouthguard sheets during thermoforming. AB - BACKGROUND: The purpose of this study was to identify changes in sheet shape during thermoforming and the effect of the model position in the molding machine on fabricated mouthguard thickness. MATERIALS AND METHODS: Ethylene vinyl acetate mouthguard sheets (3.8 mm thick) were used that had cross-stripes (10 * 10 mm), and the anteroposterior and bilateral lengths were used for measurements. Two forming machines were used: a vacuum- and a pressure-forming machine, and two heating conditions were investigated that defined as the time when sagging of the softened sheet was 15 mm (H-15) and 20 mm (H-20) below the clamp, and the length of each cross-stripes was measured. The area of each lattice was calculated using Bretschneider's formula to compare changes in sheet shape for each condition. Next, mouthguards were molded by forming machine where the working model was positioned under two different conditions: with the model anterior centered in the forming unit and with the model centered. The sheet thickness after fabrication was determined for the incisal and the molar portion, and dimensional measurements were obtained using a measuring device. Differences in the thickness were analyzed by two-way analysis of variance (anova). RESULT: In both molding machines, the change in the area under H-20 was greater than H-15. While the increase in area tended to expand from the center of the sheet in concentric circles, the difference between the central and surrounding areas was only approximately 5%. For both molding machines, differences in thickness after molding due to setting position of the model were not observed. CONCLUSION: The results showed that shape changes of the sheet during thermoforming tend to concentrically and almost uniformly expand from the center and that it is important to center the sheet and the model when positioning the model in the forming unit. PMID- 26833573 TI - An ectomycorrhizal nitrogen economy facilitates monodominance in a neotropical forest. AB - Tropical forests are renowned for their high diversity, yet in many sites a single tree species accounts for the majority of the individuals in a stand. An explanation for these monodominant forests remains elusive, but may be linked to mycorrhizal symbioses. We tested three hypotheses by which ectomycorrhizas might facilitate the dominance of the tree, Oreomunnea mexicana, in montane tropical forest in Panama. We tested whether access to ectomycorrhizal networks improved growth and survival of seedlings, evaluated whether ectomycorrhizal fungi promote seedling growth via positive plant-soil feedback, and measured whether Oreomunnea reduced inorganic nitrogen availability. We found no evidence that Oreomunnea benefits from ectomycorrhizal networks or plant-soil feedback. However, we found three-fold higher soil nitrate and ammonium concentrations outside than inside Oreomunnea-dominated forest and a correlation between soil nitrate and Oreomunnea abundance in plots. Ectomycorrhizal effects on nitrogen cycling might therefore provide an explanation for the monodominance of ectomycorrhizal tree species worldwide. PMID- 26833574 TI - A Supramolecular Approach toward Bioinspired PAMAM-Dendronized Fusion Toxins. AB - Nature has provided a highly optimized toolbox in bacterial endotoxins with precise functions dictated by their clear structural division. Inspired by this streamlined design, a supramolecular approach capitalizing on the strong biomolecular (streptavidin (SA))-biotin interactions is reported herein to prepare two multipartite fusion constructs, which involves the generation 2.0 (D2) or generation 3.0 (D3) polyamidoamine-dendronized transporter proteins (dendronized streptavidin (D3SA) and dendronized human serum albumin (D2HSA)) non covalently fused to the C3bot1 enzyme from Clostridium botulinum, a potent and specific Rho-inhibitor. The fusion constructs, D3SA-C3 and D2HSA-C3, represent the first examples of dendronized protein transporters that are fused to the C3 enzyme, and it is successfully demonstrated that the C3 Rho-inhibitor is delivered into the cytosol of mammalian cells as determined from the characteristic C3-mediated changes in cell morphology and confocal microscopy. The design circumvents the low uptake of the C3 enzyme by eukaryotic cells and holds great promise for reprogramming the properties of toxin enzymes using a supramolecular approach to broaden their therapeutic applications. PMID- 26833575 TI - PDGFRs expression in dogs affected by malignant oral melanomas: correlation with prognosis. AB - Canine malignant melanoma (CMM) is the most common canine oral tumour, and up to 70-75% of dogs in stage II-III die within 1 year after surgery. The purpose of this study was to evaluate the expression of platelet-derived growth factors receptors (PDGFR)-alpha and -beta in stage II and III CMMs and to correlate it with prognosis. PDGFRs expression was evaluated by immunohistochemistry on 48 cases of formalin-fixed CMM samples and correlated with clinical-pathological findings and outcome after surgery. PDGFRs co-expression was observed in 37.5% of cases. Positivity for PDGFR-alpha and -beta receptor was present in 54.2 and 47.9% of cases, respectively. Ki67 values >19.5% were ascertained in 66.7% of cases. Statistical analysis showed that PDGFRs co-expression and Ki67 values > 19.5% were both associated with worse prognosis. PDGFRs expression suggests a role in the pathogenesis and progression of CMM, and alpha and beta co-expression appears to be associated to worse prognosis. PMID- 26833576 TI - Total and allergen-specific immunoglobulin E in the serum and nasal mucosa of a nonallergic population. AB - BACKGROUND: There has been a growing interest in measuring allergen-specific immunoglobulin E (sIgE) directly from the nasal mucosal epithelium of individuals with sinonasal disease. However, there is currently no normative data with which to estimate sensitivity, specificity, and the appropriate positive cutoff level for new testing methods. METHODS: Twenty individuals with no history of sinonasal disease or food allergies underwent serum IgE testing and nasal mucosal brush biopsy (MBB) testing for total and sIgE to 7 common airborne allergens and 1 food allergen. The correlation between sIgE in serum and nasal samples was determined at both the 0.10-kU/L and 0.35-kU/L positive cutoff levels. RESULTS: sIgE at the 0.35-kU/L cutoff level was detected for at least 1 allergen in 7 of 20 (35%) participants in both the serum and nose. At the 0.10-kU/L cutoff level, 8 of 20 (40%) and 19 of 20 (95%) participants had sIgE to at least 1 allergen in the serum and nose, respectively. At the 0.35-kU/L cutoff level, total serum IgE levels were significantly higher when at least 1 allergen was detected in the nose (p = 0.01). There was a strong association between sIgE in the serum and nasal mucosa (p < 0.0001) at both cutoff levels. CONCLUSION: The significant association between serum and nasal samples for both total and sIgE suggests that nasal IgE and serum IgE are not independent of one another. Understanding levels of IgE in the nonallergic population will help answer the questions surrounding sensitization as new diagnostic tests for locally-present IgE become available. PMID- 26833577 TI - Peripheral Veno-Arterial Extracorporeal Membrane Oxygenation as a Bridge to Decision for Pediatric Fulminant Myocarditis. AB - It is essential to establish an appropriate initial treatment strategy for pediatric fulminant myocarditis. We reviewed eight cases of pediatric fulminant myocarditis that required extracorporeal membrane oxygenation (ECMO) from 2012 to 2015. The median age was 8 years (range 3 months-13 years), and the median body surface area was 0.89 m(2) (range 0.35-1.34 m(2) ). Peripheral veno-arterial ECMO was initially applied, and we evaluated whether heart decompression was sufficient. If the pump flow was insufficient, central cannulation was performed via median sternotomy (central ECMO). The need for subsequent ventricular assist device (VAD) support was determined 72 h after ECMO initiation. Six patients were bridged to recovery using peripheral ECMO support only (for 3-11 days), whereas two required VAD support. One patient was switched to central ECMO before VAD implantation. Three patients died of multiorgan failure, even though cardiac function recovered in two of those patients. The duration from hospital arrival to ECMO initiation was shorter in the survival (3.3 +/- 1.3 h; range 1.6-4.7 h) than in the nonsurvival group (32 +/- 28 h; range 0.7-55 h). Peripheral ECMO can be useful as a bridge to decision for pediatric fulminant myocarditis, which is frequently followed by a successful bridge to recovery. It is important to determine whether ECMO support should be initiated before organ dysfunction advances to preserve organ function, which provides a better bridge to subsequent VAD therapy and heart transplant or recovery. PMID- 26833578 TI - Synthetic Biology and the Moral Significance of Artificial Life: A Reply to Douglas, Powell and Savulescu. AB - I discuss the moral significance of artificial life within synthetic biology via a discussion of Douglas, Powell and Savulescu's paper 'Is the creation of artificial life morally significant'. I argue that the definitions of 'artificial life' and of 'moral significance' are too narrow. Douglas, Powell and Savulescu's definition of artificial life does not capture all core projects of synthetic biology or the ethical concerns that have been voiced, and their definition of moral significance fails to take into account the possibility that creating artificial life is conditionally acceptable. Finally, I show how several important objections to synthetic biology are plausibly understood as arguing that creating artificial life in a wide sense is only conditionally acceptable. PMID- 26833579 TI - Intraventricular Isovolumic Relaxation Flow Patterns Studied by Using Vector Flow Mapping. AB - AIMS: The purpose of this study was to characterize isovolumic relaxation flow (IRF) in the left ventricle (LV) in patients with a wide spectrum of LV dysfunction. METHODS: Color Doppler flow imaging was performed in 61 patients with coronary artery disease, 29 patients with dilated cardiomyopathy, and 41 healthy controls. Vector flow mapping was used to analyze the Doppler data. RESULTS: IRF patterns were divided into three types: pattern A, an apically directed flow; pattern B, a bidirectional flow with small scattered vortices; and pattern C, a large vortex persisting throughout the entire isovolumic relaxation (IVR) period. All controls demonstrated an IRF corresponding to pattern A. Of the 90 patients, 42 demonstrated IRF as pattern A, 26 as pattern B, and 22 as pattern C. There were significant differences among the subgroups of patients with different IRF patterns and the control group in LV-ejection fraction, size, wall motion score index, apical wall-motion score index, systolic and diastolic mitral annular velocities, ratio of the mitral inflow E velocity to early diastolic mitral annular velocity (E/e'), and left atrial diameter (all P < 0.05). In the patient group, a higher wall-motion score index independently predicted the IRF pattern. In patients with severe LV dysfunction, a higher E/e' ratio was the independent predictor of the persistence of a large vortex during the IVR period. CONCLUSIONS: The IRF pattern is associated with LV function. A large intraventricular vortex persisting during the IVR period should be indicative of increasingly depressed LV function. PMID- 26833580 TI - High-Performance Green OLEDs Using Thermally Activated Delayed Fluorescence with a Power Efficiency of over 100 lm W(-1). AB - A green organic light-emitting device (OLED) with an extremely high power efficiency of over 100 lm W(-1) is realized through energy transfer from an exciplex. An optimized OLED showed a maximum external efficiency of 25.7%, and a power efficiency of 79.4 lm W(-1) at 1000 cd m(-2) , which is 1.6-times higher than that of state-of-the-art green thermally activated delayed fluorescence (TADF) OLEDs. PMID- 26833581 TI - Trichloromethylthiolation of N-Heterocycles: Practical and Completely Regioselective. AB - The first trichloromethylthiolation of a broad range of indoles and pyrroles is reported employing bench-stable N-trichloromethylthiosaccharin as reagent. This methodology is highly regioselective, exhibits high functional group tolerance, and provides access to two previously unknown classes of potentially bioactive compounds. PMID- 26833582 TI - Interaction Study and Reactivity of Zr(IV) -Substituted Wells-Dawson Polyoxometalate towards Hydrolysis of Peptide Bonds in Surfactant Solutions. AB - The interaction between the 1:2 Zr(IV) :Wells-Dawson complex, K15 H[Zr(alpha2 -P2 W17 O61 )2] (1), and a range of surfactants was studied in detail with the aim of developing metal-substituted POMs as potential artificial proteases for membrane proteins. The surfactants include the positively charged cetyl(trimethyl)ammonium bromide (CTAB), the negatively charged sodium dodecyl sulfate (SDS), the neutral Triton X-100 (TX-100), and zwitterionic 3-[dodecyl(dimethyl)ammonio]-1 propanesulfonate (Zw3-13) and 3-[dimethyl(3-{[(3alpha,5beta,7alpha,12alpha) 3,7,12-trihydroxy-24-oxocholan-24-yl]amino}propyl)ammonio]-1-propanesulfonate (CHAPS). A combination of multinuclear (1)H, (13)C, and (31) P NMR spectroscopy, (1)H diffusion-ordered NMR spectroscopy ((1)H DOSY), and nuclear Overhauser effect spectroscopy (NOESY) was used to examine the interaction between 1 and each surfactant on the molecular level. Cationic surfactant CTAB caused precipitation of 1 due to strong electrostatic interactions, while the anionic SDS and neutral TX-100 surfactants did not exhibit any interaction at neutral pD. (1)H DOSY NMR spectroscopy indicated an interaction between 1 and zwitterionic surfactants Zw3-12 and CHAPS, which occurs via the positively charged ammonium group in the surfactant molecule. In the presence of anionic, neutral, and zwitterionic surfactants, 1 preserves its catalytic activity towards the hydrolysis of the peptide bond in the dipeptide glycyl-l-histidine (GH). The fastest hydrolysis was observed at pD 7.0 and could be rationalized by taking into account pD-dependent speciation of 1 and coordination properties of GH. PMID- 26833583 TI - Polymeric Gene Carriers Bearing Pendant beta-Cyclodextrin: The Relevance of Glycoside Permethylation on the "In Vitro" Cell Response. AB - The incorporation of cyclodextrins (CDs) to nonviral cationic polymer vectors is very attractive due to recent studies that report a clear improvement of their cytocompatibility and transfection efficiency. However, a systematic study on the influence of the CD derivatization is still lacking. In this work, the relevance of beta-CD permethylation has been addressed by preparing and evaluating two series of copolymers of the cationic N-ethyl pyrrolidine methacrylamide (EPA) and styrenic units bearing pendant hydroxylated and permethylated beta-CDs (HCDSt and MeCDSt, respectively). For both cell lines, CDs permethylation shows a strong influence on plasmid DNA complexation, "in vitro" cytocompatibility and transfection efficiency of the resulting copolymers over two murine cell lines. While the incorporation of the hydroxylated CD moiety increased the cytotoxicity of the copolymers in comparison with their homopolycationic counterpart, the permethylated copolymers have shown full cytocompatibility as well as superior transfection efficiency than the controls. This behavior has been related to the different chemical nature of both units and tentatively to a different distribution of units along the polymeric chains. Cellular internalization analysis with fluorescent copo-lymers supports this behavior. PMID- 26833584 TI - Correlation of Urine and Serum Biomarkers with Renal Damage and Survival in Dogs with Naturally Occurring Proteinuric Chronic Kidney Disease. AB - BACKGROUND: Urine protein loss is common in dogs with chronic kidney disease (CKD). HYPOTHESIS/OBJECTIVES: To evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD. ANIMALS: One hunderd and eighty dogs with naturally occurring kidney disease. METHODS: Retrospective study using urine, serum, and renal biopsies from dogs with kidney disease, 91% of which had proteinuric CKD. Biomarkers were evaluated and correlated with pathologic renal damage, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined. RESULTS: Fractional excretions of immunogloblin M (IgM_FE) and immunoglobulin G (IgG_FE) correlated most strongly with glomerular damage based on light microscopy (r = 0.58 and 0.56, respectively; P < .01). Serum creatinine (SCr) correlated most strongly with TI damage (r = 0.70, P < .01). Urine IgM/creatinine and urine NAG/creatinine had the highest sensitivity (75%) and specificity (78%) for detection of immune complex-mediated glomerulonephritis. Although individually most biomarkers were significantly associated with decreased survival time (P < .05), in a multivariate analysis, SCr, IgM_FE, and glomerular damage based on transmission electron microscopy (TEM) were the only biomarkers significantly associated with survival time (SCr: P = .001; IgM_FE: P = .008; TEM: P = .017). CONCLUSIONS AND CLINICAL IMPORTANCE: Novel urine biomarkers and FEs are useful for detection of glomerular and TI damage in dogs with proteinuric CKD and might predict specific disease types and survival. PMID- 26833585 TI - Hepatic expression of proteasome subunit alpha type-6 is upregulated during viral hepatitis and putatively regulates the expression of ISG15 ubiquitin-like modifier, a proviral host gene in hepatitis C virus infection. AB - The interferon-stimulated gene 15 (ISG15) plays an important role in the pathogenesis of hepatitis C virus (HCV) infection. ISG15-regulated proteins have previously been identified that putatively affect this proviral interaction. The present observational study aimed to elucidate the relation between ISG15 and these host factors during HCV infection. Transcriptomic and proteomic analyses were performed using liver samples of HCV-infected (n = 54) and uninfected (n = 10) or HBV-infected controls (n = 23). Primary human hepatocytes (PHH) were treated with Toll-like receptor ligands, interferons and kinase inhibitors. Expression of ISG15 and proteasome subunit alpha type-6 (PSMA6) was suppressed in subgenomic HCV replicon cell lines using specific siRNAs. Comparison of hepatic expression patterns revealed significantly increased signals for ISG15, IFIT1, HNRNPK and PSMA6 on the protein level as well as ISG15, IFIT1 and PSMA6 on the mRNA level in HCV-infected patients. In contrast to interferon-stimulated genes, PSMA6 expression occurred independent of HCV load and genotype. In PHH, the expression of ISG15 and PSMA6 was distinctly induced by poly(I:C), depending on IRF3 activation or PI3K/AKT signalling, respectively. Suppression of PSMA6 in HCV replicon cells led to significant induction of ISG15 expression, thus combined knock-down of both genes abrogated the antiviral effect induced by the separate suppression of ISG15. These data indicate that hepatic expression of PSMA6, which is upregulated during viral hepatitis, likely depends on TLR3 activation. PSMA6 affects the expression of immunoregulatory ISG15, a proviral factor in the pathogenesis of HCV infection. Therefore, the proteasome might be involved in the enigmatic interaction between ISG15 and HCV. PMID- 26833586 TI - Socioeconomic status and anthropometric changes-A meta-analytic approach from seven German cohorts. AB - OBJECTIVE: To study the association between socioeconomic status (SES) and annual relative change in anthropometric markers in the general German adult population. METHODS: Longitudinal data of 56,556 participants aged 18-83 years from seven population-based German cohort studies (CARLA, SHIP, KORA, DEGS, EPIC-Heidelberg, EPIC-Potsdam, PopGen) were analyzed by meta-analysis using a random-effects model. The indicators of SES were education and household income. RESULTS: On average, all participants gained weight and increased their waist circumference over the study's follow-up period. Men and women in the low education group had a 0.1 percentage points greater annual increase in weight (95% CI men: 0.06-0.20; and women: 0.06-0.12) and waist circumference (95% CI men: 0.01-0.45; and women: 0.05-0.22) than participants in the high education group. Women with low income had a 0.1 percentage points higher annual increase in weight (95% CI 0.00-0.15) and waist circumference (95% CI 0.00-0.14) than women with high income. No association was found for men between income and obesity markers. CONCLUSIONS: Participants with lower SES (education and for women also income) gained more weight and waist circumference than those with higher SES. These results underline the necessity to evaluate the risk of weight gain based on SES to develop more effective preventive measures. PMID- 26833587 TI - Treprostinil Iontophoresis Improves Digital Blood Flow during Local Cooling in Systemic Sclerosis. AB - INTRODUCTION: Severe Raynaud's syndrome and DUs are the most prevalent manifestations of SSc peripheral microvascular disease. We tested whether treprostinil iontophoresis on the finger pad of patients with SSc would improve digital blood flow during hand cooling. METHODS: Eleven patients with limited cutaneous SSc underwent a double-blinded iontophoresis of treprostinil (2.56 * 10(-4) M during two hours) and placebo (NaCl 0.9%) on two finger pads. Then, the hand was inserted for 30 minutes in a fenestrated cooling box at 8 degrees C, and skin blood flow was recorded continuously using LSCI. RESULTS: During the local cooling, CVC was significantly higher at the treprostinil site than at the placebo site and remained higher 30 minutes after the test. CONCLUSIONS: In patients with SSc, digital treprostinil iontophoresis shifts skin blood flow upward during local cooling of the hand and during the initial rewarming phase. Digital treprostinil iontophoresis should now be tested in larger scale studies. PMID- 26833588 TI - Facile Access to Fluoroaromatic Molecules by Transition-Metal-Free C-F Bond Cleavage of Polyfluoroarenes: An Efficient, Green, and Sustainable Protocol. AB - The creation of new bonds via C-F bond cleavage of polyfluoroarenes has proven to be an important and powerful tool in synthetic chemistry. Using such a strategy, a myriad of valuable partially fluoroaromatic molecules and building blocks can be obtained. The transition-metal-free nucleophilic aromatic substitution (SN Ar) strategy has aroused the continuing interest of researchers due to its simple, mild, economical, and environmentally benign characteristics, which have been successfully applied to C-F bond functionalizations. In this account, we present a summary of the recent investigations of polyfluoroarenes involving SN Ar reactions and discuss some of our recent endeavors in the construction of partially fluoroaromatic molecules. Through this strategy, many new bonds including C-C, C-N, C-O, C-S, and C-H bonds can be created. Additionally, brief discussions on the transformation mechanisms are also provided. Finally, we discuss the existing limitations of the SN Ar reactions of polyfluoroarenes as well as our perspective on the future development of this chemistry. PMID- 26833589 TI - Somaclonal variation does not preclude the use of rice transformants for genetic screening. AB - Rice (Oryza sativa) is one of the world's most important crops. Rice researchers make extensive use of insertional mutants for the study of gene function. Approximately half a million flanking sequence tags from rice insertional mutant libraries are publicly available. However, the relationship between genotype and phenotype is very weak. Transgenic plant assays have been used frequently for complementation, overexpression or antisense analysis, but sequence changes caused by callus growth, Agrobacterium incubation medium, virulence genes, transformation and selection conditions are unknown. We used high-throughput sequencing of DNA from rice lines derived from Tainung 67 to analyze non transformed and transgenic rice plants for mutations caused by these parameters. For comparison, we also analyzed sequence changes for two additional rice varieties and four T-DNA tagged transformants from the Taiwan Rice Insertional Mutant resource. We identified single-nucleotide polymorphisms, small indels, large deletions, chromosome doubling and chromosome translocations in these lines. Using standard rice regeneration/transformation procedures, the mutation rates of regenerants and transformants were relatively low, with no significant differences among eight tested treatments in the Tainung 67 background and in the cultivars Taikeng 9 and IR64. Thus, we could not conclusively detect sequence changes resulting from Agrobacterium-mediated transformation in addition to those caused by tissue culture-induced somaclonal variation. However, the mutation frequencies within the two publically available tagged mutant populations, including TRIM transformants or Tos17 lines, were about 10-fold higher than the frequency of standard transformants, probably because mass production of embryogenic calli and longer callus growth periods were required to generate these large libraries. PMID- 26833590 TI - Interstitial changes in asthma-COPD overlap syndrome. AB - INTRODUCTION: Asthma-COPD overlap syndrome (ACOS) is the widely recognized syndrome of asthma and COPD coexisting together. Cigarette smoking is a known risk factor for ACOS and is reported to be associated with interstitial lung diseases (ILDs). Subclinical ILDs have been frequently detected in smokers' lungs by radiological and pathological examinations. This finding raises the possibility that unrecognized mild interstitial changes take place in lungs with ACOS. OBJECTIVES: We sought to determine whether interstitial changes were present in the lungs of patients with ACOS and to characterize the clinical features of ACOS with interstitial changes. METHODS: Thirty patients with ACOS were enrolled in the study (26 men and 4 women, mean age 70.1 years). Interstitial changes in the lungs were estimated by high-resolution computed tomography (HRCT). Clinical findings and airway wall thickness on HRCT were assessed retrospectively and compared between ACOS patients with and without interstitial changes. RESULTS: Interstitial changes were found in seven patients (23.3%) with ACOS who had HRCT. The age and smoking amount were significantly higher in ACOS with interstitial changes than in ACOS without interstitial changes. ACOS with interstitial changes tended to have a higher rate of fungal sensitisation. Multivariate analysis showed pack-years were significantly related to the presence of interstitial changes. Airway walls assessed by HRCT were significantly thicker in ACOS with interstitial changes than in ACOS without interstitial changes. CONCLUSIONS: The ACOS patients with interstitial changes were heavier smokers and had thicker airway walls on HRCT compared to the ACOS patients without interstitial changes. PMID- 26833592 TI - Dithienophosphole-Based Phosphinamides with Intriguing Self-Assembly Behavior. AB - A new, highly adaptable type of phosphinamide-based hydrogen bonding is representatively demonstrated in pi-conjugated phosphole materials. The rotational flexibility of these intermolecular P=O-H-N hydrogen bonds is demonstrated by X-ray crystallography and variable-concentration NMR spectroscopy. In addition to crystalline compounds, phosphinamide hydrogen bonding was successfully introduced into the self-assembly of soft crystals, liquid crystals, and organogels, thus highlighting the high general value of this type of interaction for the formation of organic soft materials. PMID- 26833591 TI - Predictors and prognostic significance of tachycardiomyopathy: insights from a cohort of 1269 patients undergoing atrial flutter ablation. AB - BACKGROUND: Atrial flutter-related tachycardiomyopathy (AFL-TCM) is a rare and treatable cause of heart failure. Little is known about its epidemiology and long term prognosis. Our aims are to determine the prevalence, predictors and outcomes of AFL-TCM. METHODS AND RESULTS: A total of 1269 patients were referred for radiofrequency ablation of AFL between January 1996 and September 2014; 184 had reduced left ventricular ejection fraction (LVEF <40%). At 6 months after AFL ablation, 103 patients (8.1% of the population, 56% of patients with baseline LVEF <40%) had marked LVEF improvement: these were considered to have AFL-TCM. Patients with persisting reduced LVEF were considered to have systolic dysfunction unrelated to AFL. Patients were followed for a median (percentile25 75 ) of 1.15 (0.4-2.8) years. Patients with AFL-TCM were younger, had lower prevalence of ischaemic cardiomyopathy and used less antiarrhythmic drugs than patients with systolic dysfunction unrelated to AFL. In multivariable analysis, ischemic cardiomyopathy [odds ratio (OR) = 0.32, 95% confidence interval (CI) 0.15-0.68) P = 0.003] and prescription of antiarrhythmic drug before ablation [OR = 0.41, 95% CI 0.20-0.84, P = 0.02] were significantly associated with a lower probability of LVEF improvement during follow-up. Patients with AFL-TCM had similar survival to patients without systolic dysfunction at baseline [hazard ratio (HR) = 0.96 95% CI 0.34-2.65, P = 0.929], whereas patients with systolic dysfunction unrelated to AFL had higher mortality rates compared with patients without systolic dysfunction at baseline [HR = 2.88, 95% CI 1.45-5.72, P = 0.002]. CONCLUSIONS: Marked LVEF improvement was observed in 56% of patients with baseline LVEF <40% at 6 months after ablation. These patients had similar survival to patients without baseline systolic dysfunction, whereas patients who remained with LVEF <40% had a threefold increase in mortality rates. PMID- 26833594 TI - The need for a conceptual framework in psychiatry acknowledging complexity while avoiding defeatism. PMID- 26833593 TI - Qualitative Exploration of Illness Perceptions of Rheumatoid Arthritis in the General Public. AB - Treating patients with rheumatoid arthritis (RA) within three months of symptom onset leads to significantly improved outcomes. However, many people delay seeking medical attention. In order to understand the reasons for this delay, it is important to have a thorough understanding of public perceptions about RA. The current study investigated these perceptions using the Self-Regulation Model (SRM) as a framework to explain how health behaviour is influenced by illness perceptions (prototypes) through qualitative interviews with 15 members of the public without RA. Interviews were audio-recorded, transcribed and analysed using framework analysis based on SRM illness perceptions. Both accurate and inaccurate perceptions about the identity, causes, consequences, controllability and timeline of RA were identified. This highlights opportunities to enhance public knowledge about RA. These findings further support the utility of exploring prototypical beliefs of illness, suggesting their potential role in influencing help-seeking behaviours and identifying probable drivers/barriers to early presentation. (c) 2016 The Authors Musculoskeletal Care Published by John Wiley & Sons Ltd. PMID- 26833595 TI - Dopamine and the aberrant salience hypothesis of schizophrenia. PMID- 26833596 TI - The nature of psychiatric disorders. AB - A foundational question for the discipline of psychiatry is the nature of psychiatric disorders. What kinds of things are they? In this paper, I review and critique three major relevant theories: realism, pragmatism and constructivism. Realism assumes that the content of science is real and independent of human activities. I distinguish two "flavors" of realism: chemistry-based, for which the paradigmatic example is elements of the periodic table, and biology-based, for which the paradigm is species. The latter is a much better fit for psychiatry. Pragmatism articulates a sensible approach to psychiatric disorders just seeking categories that perform well in the world. But it makes no claim about the reality of those disorders. This is problematic, because we have a duty to advocate for our profession and our patients against other physicians who never doubt the reality of the disorders they treat. Constructivism has been associated with anti-psychiatry activists, but we should admit that social forces play a role in the creation of our diagnoses, as they do in many sciences. However, truly socially constructed psychiatric disorders are rare. I then describe powerful arguments against a realist theory of psychiatric disorders. Because so many prior psychiatric diagnoses have been proposed and then abandoned, can we really claim that our current nosologies have it right? Much of our current nosology arose from a series of historical figures and events which could have gone differently. If we re-run the tape of history over and over again, the DSM and ICD would not likely have the same categories on every iteration. Therefore, we should argue more confidently for the reality of broader constructs of psychiatric illness rather than our current diagnostic categories, which remain tentative. Finally, instead of thinking that our disorders are true because they correspond to clear entities in the world, we should consider a coherence theory of truth by which disorders become more true when they fit better into what else we know about the world. In our ongoing project to study and justify the nature of psychiatric disorders, we ought to be broadly pragmatic but not lose sight of an underlying commitment, despite the associated difficulties, to the reality of psychiatric illness. PMID- 26833598 TI - Tech giants enter mental health. PMID- 26833597 TI - Treatment engagement of individuals experiencing mental illness: review and update. AB - Individuals living with serious mental illness are often difficult to engage in ongoing treatment, with high dropout rates. Poor engagement may lead to worse clinical outcomes, with symptom relapse and rehospitalization. Numerous variables may affect level of treatment engagement, including therapeutic alliance, accessibility of care, and a client's trust that the treatment will address his/her own unique goals. As such, we have found that the concept of recovery oriented care, which prioritizes autonomy, empowerment and respect for the person receiving services, is a helpful framework in which to view tools and techniques to enhance treatment engagement. Specifically, person-centered care, including shared decision making, is a treatment approach that focuses on an individual's unique goals and life circumstances. Use of person-centered care in mental health treatment models has promising outcomes for engagement. Particular populations of people have historically been difficult to engage, such as young adults experiencing a first episode of psychosis, individuals with coexisting psychotic and substance use disorders, and those who are homeless. We review these populations and outline how various evidence-based, recovery-oriented treatment techniques have been shown to enhance engagement. Our review then turns to emerging treatment strategies that may improve engagement. We focus on use of electronics and Internet, involvement of peer providers in mental health treatment, and incorporation of the Cultural Formulation Interview to provide culturally competent, person-centered care. Treatment engagement is complex and multifaceted, but optimizing recovery-oriented skills and attitudes is essential in delivery of services to those with serious mental illness. PMID- 26833599 TI - Should psychiatry deal only with mental disorders without an identified medical aetiology? PMID- 26833600 TI - What can we learn from the high rates of schizophrenia in people with 22q11.2 deletion syndrome? PMID- 26833601 TI - Psychiatric classifications: validity and utility. AB - Despite historical assumptions to the contrary, there is little evidence that the majority of recognized mental disorders are separated by natural boundaries. Diagnostic categories defined by their clinical syndromes should be regarded as 'valid' only if they have been shown to be truly discrete entities. Most diagnostic concepts in psychiatry have not been demonstrated to be valid in this sense, though many possess 'utility' by virtue of the information they convey about presenting symptoms, outcome, treatment response and, in some instances, aetiology. While researchers in genetics, neurobiology and population epidemiology are increasingly more likely to adopt a continuum/dimensional view of the variation in symptomatology, clinicians prefer to hold on to the categorical approach embodied in current classifications such as ICD-10 and DSM 5. Both points of view have plausible justification in their respective contexts, but the way forward may be in their conceptual reconciliation. PMID- 26833602 TI - A report card on the utility of psychiatric diagnosis. PMID- 26833603 TI - Against utility. PMID- 26833604 TI - Utility without validity is useless. PMID- 26833605 TI - We need science to be useful too. PMID- 26833606 TI - Would the use of dimensional measures improve the utility of psychiatric diagnoses? PMID- 26833607 TI - Variation and validation: the example of schizophrenia. PMID- 26833608 TI - Clinical, socio-demographic and psychological characteristics in individuals with persistent psychotic experiences with and without a "need for care". AB - Individuals reporting persistent psychotic experiences (PEs) in the general population, but without a "need for care", are a unique group of particular importance in identifying risk and protective factors for psychosis. We compared people with persistent PEs and no "need for care" (non-clinical, N=92) with patients diagnosed with a psychotic disorder (clinical, N=84) and controls without PEs (N=83), in terms of their phenomenological, socio-demographic and psychological features. The 259 participants were recruited from one urban and one rural area in the UK, as part of the UNIQUE (Unusual Experiences Enquiry) study. Results showed that the non-clinical group experienced hallucinations in all modalities as well as first-rank symptoms, with an earlier age of onset than in the clinical group. Somatic/tactile hallucinations were more frequent than in the clinical group, while commenting and conversing voices were rare. Participants in the non-clinical group were differentiated from their clinical counterparts by being less paranoid and deluded, apart from ideas of reference, and having fewer cognitive difficulties and negative symptoms. Unlike the clinical group, they were characterized neither by low psychosocial functioning nor by social adversity. However, childhood trauma featured in both groups. They were similar to the controls in psychological characteristics: they did not report current emotional problems, had intact self-esteem, displayed healthy schemas about the self and others, showed high life satisfaction and well-being, and high mindfulness. These findings support biopsychosocial models postulating that environmental and psychological factors interact with biological processes in the aetiology of psychosis. While some PEs may be more malign than others, lower levels of social and environmental adversity, combined with protective factors such as intact IQ, spirituality, and psychological and emotional well being, may reduce the likelihood of persistent PEs leading to pathological outcomes. Future research should focus on protective factors and determinants of well-being in the context of PEs, rather than exclusively on risk factors and biomarkers of disease states. PMID- 26833609 TI - Lithium vs. valproate vs. olanzapine vs. quetiapine as maintenance monotherapy for bipolar disorder: a population-based UK cohort study using electronic health records. AB - It is unclear which maintenance treatment for bipolar disorder is superior in clinical practice. Randomized controlled head-to-head trials of available drugs either do not exist or are inconclusive. We aimed to compare rates of monotherapy treatment failure in individuals prescribed lithium, valproate, olanzapine or quetiapine by a population-based cohort study using electronic health records. 5,089 patients with bipolar disorder were prescribed lithium (N=1,505), valproate (N=1,173) olanzapine (N=1,366) or quetiapine (N=1,075) as monotherapy. Treatment failure was defined as time to stopping medication or add-on of another mood stabilizer, antipsychotic, antidepressant or benzodiazepine. In unadjusted analyses, the duration of successful monotherapy was longest in individuals treated with lithium. Treatment failure had occurred in 75% of those prescribed lithium by 2.05 years (95% CI: 1.63-2.51), compared to 0.76 years (95% CI: 0.64 0.84) for those prescribed quetiapine, 0.98 years (95% CI: 0.84-1.18) for those prescribed valproate, and 1.13 years for those prescribed olanzapine (95% CI: 1.00-1.31). Lithium's superiority remained in a propensity score matched analysis; when treatment failure was defined as stopping medication or add-on of a mood stabilizer or antipsychotic; and when treatment failure was restricted to more than three months after commencing the study drug. Lithium appears to be more successful as monotherapy maintenance treatment than valproate, olanzapine or quetiapine. Lithium is often avoided because of its side effect profile, but alternative treatments may reduce the time to being prescribed more than one drug, with potential additive side effects of these treatments. PMID- 26833610 TI - Bereavement after sibling death: a population-based longitudinal case-control study. AB - The objective of this study was to examine mental disorders and treatment use among bereaved siblings in the general population. Siblings (N=7243) of all deceased children in the population of Manitoba, Canada who died between 1984 and 2009 were matched 1:3 to control siblings (N=21,729) who did not have a sibling die in the study period. Generalized estimating equations were used to compare the two sibling groups in the two years before and after the index child's death on physician-diagnosed mental disorders and treatment utilization, with adjustment for confounding factors including pre-existing mental illness. Analyses were stratified by age of the bereaved (<13 vs. 13+). Results revealed that, in the two years after the death of the child, bereaved siblings had significantly higher rates of mental disorders than control siblings, even after adjusting for pre-existing mental illness. When comparing the effect of a child's death on younger versus older siblings, the rise in depression rates from pre death to post-death was significantly higher for siblings aged under 13 (p<0.0001), increasing more than 7-fold (adjusted relative rate, ARR=7.25, 95% CI: 3.65-14.43). Bereaved siblings aged 13+ had substantial morbidity in the two years after the death: 25% were diagnosed with a mental disorder (vs. 17% of controls), and they had higher rates of almost all mental disorder outcomes compared to controls, including twice the rate of suicide attempts (ARR=2.01, 95% CI: 1.29-3.12). Siblings in the bereaved cohort had higher rates of alcohol and drug use disorders already before the death of their sibling. In conclusion, the death of a child is associated with considerable mental disorder burden among surviving siblings. Pre-existing health problems and social disadvantage do not fully account for the increase in mental disorder rates. PMID- 26833612 TI - Supported accommodation for people with mental health problems. PMID- 26833611 TI - Lessons learned from unintended consequences about erasing the stigma of mental illness. AB - Advocates and scientists have partnered to develop and evaluate programs meant to erase the egregious effects of the different forms of stigma. Enough evidence has been collected to yield lessons about approaches to stigma change. Some of the most insightful of these lessons emerge from unintended consequences of good intentioned approaches, and are the focus of this paper. They include the limited benefits of education especially when compared to contact, beating stigma is more than changing words, beware pity as a message, understand the competing agendas of stigma change, replace ideas of normalcy with solidarity, and avoid framing self-stigma as the problem of people with mental illness and not of society. The paper ends with consideration of the back seat role that psychiatrists and other mental health providers should have in stigma change. PMID- 26833613 TI - New approaches to interventions for refugee children. PMID- 26833614 TI - Why are some individuals more resilient than others: the role of social support. PMID- 26833616 TI - Sustaining Individual Placement and Support (IPS) services: the IPS Learning Community. PMID- 26833615 TI - Towards an international expert consensus for defining treatment response, remission, recovery and relapse in obsessive-compulsive disorder. PMID- 26833617 TI - Suicidal ideation and suicide attempts in Greece during the economic crisis: an update. PMID- 26833618 TI - New analytic strategies help answer the controversial question of whether alliance is therapeutic in itself. PMID- 26833619 TI - Clinical efficacy and safety of repetitive transcranial magnetic stimulation in acute bipolar depression. PMID- 26833620 TI - WPA Position Statement on Spirituality and Religion in Psychiatry. PMID- 26833621 TI - Update on WPA scientific publications. PMID- 26833622 TI - Acquired phototrophy stabilises coexistence and shapes intrinsic dynamics of an intraguild predator and its prey. AB - In marine ecosystems, acquired phototrophs - organisms that obtain their photosynthetic ability by hosting endosymbionts or stealing plastids from their prey - are omnipresent. Such taxa function as intraguild predators yet depend on their prey to periodically obtain chloroplasts. We present a new theory for the effects of acquired phototrophy on community dynamics by analysing a mathematical model of this predator-prey interaction and experimentally verifying its predictions with a laboratory model system. We show that acquired phototrophy stabilises coexistence, but that the nature of this coexistence exhibits a 'paradox of enrichment': as light increases, the coexistence between the acquired phototroph and its prey transitions from a stable equilibrium to boom-bust cycles whose amplitude increases with light availability. In contrast, heterotrophs and mixotrophic acquired phototrophs (that obtain < 30% of their carbon from photosynthesis) do not exhibit such cycles. This prediction matches field observations, in which only strict ( > 95% of carbon from photosynthesis) acquired phototrophs form blooms. PMID- 26833623 TI - Pancreas Transplantation From Living Donors: A Single Center Experience of 20 Cases. AB - Living donor pancreas transplantation (LDPT) has several advantages over deceased donor pancreas transplantation (DDPT), including better HLA matching, shorter ischemic time, and shorter waiting time. It remains an attractive option for diabetes mellitus (DM) patients with end stage renal disease. We reviewed 20 cases of LDPT performed in Asan Medical Center between October 1992 and March 2015. Six cases (30%) were pancreas transplantation alone (PTA), and the rest (70%) were simultaneous pancreas and kidney transplantation (SPK). Relations of donor and recipient were parents in 7 (35%), siblings in 6 (30%), spouse in 6 (30%), and cousin in 1 (5%). Graft survival in SPK at 1, 3, 5, and 10 years was 91.7%, 83.3%, 83.3%, and 83.3%, respectively, and that in PTA recipients was 50%, 33.3%, 16.7%, and 16.7%, respectively (p = 0.005). Causes of graft failure in SPK were thrombosis (one case), and rejection (one case), whereas those in PTA were noncompliance (two cases), thrombosis (one case), reflux pancreatitis (one case), and chronic rejection (one case). In terms of pancreas exocrine drainage, two grafts (25%) maintained their function in bladder drainage, while all grafts maintained in enteric drainage p < 0.05). Seven (35%) donors experienced minor pancreatic juice leakage and one underwent reoperation due to postoperative hematoma. Most donors maintained normoglycemia and normal renal function. However, two donors developed DM (at 1 and 90 months postdonation), and were treated with oral hypoglycemic agents. Graft survival in PTA recipients was poorer than in SPK due to poor compliance and bladder drainage-related problems. The surgical and metabolic complication rates of donors can be minimized by applying strict donor criteria. Therefore, LDPT with enteric drainage is an acceptable treatment for SPK. PMID- 26833625 TI - Insight of Dogs' Inner Mandible Anatomy using Mathematical Models. AB - This study was performed in a sample of 20 dogs (n = 20) and aimed to: (1) characterize the mandible height (Mh), mandibular canal height (MCh) and distance between the inter-dental alveolar margin and the mandibular canal (dIAM-MC) dimensions, and (2) to develop mathematical models that express the insight's mandible anatomy of those important mandible structural elements allowing the prediction of their dimensions using physical parameters such as patient body weight (Wg) and the canine tooth width at the free gingival margin level-(wCGM). Lateral-view X-rays of both sides of the skull were taken for all the individuals. Three mathematical prediction models were developed to calculate Mh, MCh and dIAM-MC. Achieved proportions of the mandible considered parameters regarding its height were of 36.45% for MCh, 50.90% for dMAI-MC and 12.65% for vMC. Statistically significant differences were registered between the Wg and wCGM (P = 0.00), Mh (P = 0.00), MCh (P = 0.00) and dIAM-MC (P = 0.00). Only the Wg presented a strong correlation with the wCGM (R = 0.58), Mh (R = 0.70), dIAM MC (R = 0.60) and MCh (R = 0.68). These models will allow a clinician to estimate the size of the mandible structures by only using data obtained during the physiological examination, with a sufficiently high prediction capacity and a very low standard error. The study points out the relationships of physiological parameters such as Wg and wCGM with mandible anatomical structural elements considered as important in oral surgery. The results of this study give the surgeon a new additional tool providing more information on the mandible anatomical structures and its relationships. This reduces the risk of iatrogenic lesions during the oral surgical procedures and improves patient safety. PMID- 26833624 TI - Clara cell protein 16 and eosinophil cationic protein production in chronically inflamed sinonasal mucosa. AB - BACKGROUND: Clara cell protein 16 (CC16) is an anti-inflammatory protein mainly expressed in the epithelial cells in the upper and lower airways. Eosinophil cationic protein (ECP) is an important marker of eosinophil activity in chronic inflammatory sinonasal diseases. The aim of this study was to evaluate mucosal production of CC16 and ECP in patients with perennial allergic rhinitis (PAR), nonallergic and allergic patients with chronic rhinosinusitis with nasal polyposis (CRSwNP), before and after nasal corticosteroid administration. METHODS: Twenty patients with PAR, 20 nonallergic CRSwNP patients, 20 allergic CRSwNP patients, and 20 healthy controls were included. Mucosal cytology samples were taken from all participants for quantification of eosinophils. CC16 and ECP levels were measured in the nasal secretion samples. The patients with chronic sinonasal inflammation were treated with fluticasone nasal spray for 14 days. Nasal symptoms assessment, cytological examination, and CC16 and ECP nasal fluid measurements were performed before and after the corticosteroid treatment. RESULTS: Mean CC16 concentrations in nasal secretions were significantly lower in patients with PAR (p < 0.05) and allergic CRSwNP patients (p < 0.01) compared to controls. Mean ECP levels were significantly higher in patients with PAR, nonallergic CRSwNP patients, and allergic CRSwNP patients compared to the control group (p < 0.001, p < 0.01, p < 0.001, respectively). After nasal corticosteroid therapy, we found a highly significant increase of CC16 (p < 0.001) and reduction of ECP (p < 0.001) in nasal secretions in all 3 groups of patients. CONCLUSION: CC16 and ECP measured in nasal secretions could be reliable markers for assessment of the recovery function of sinonasal mucosa during corticosteroid treatment. PMID- 26833626 TI - Ethical Obligations in the Face of Dilemmas Concerning Patient Privacy and Public Interests: The Sasebo Schoolgirl Murder Case. AB - A murder case that had some features in common with the Tarasoff case occurred in Sasebo City, Japan, in 2014. A 15-year-old high school girl was murdered and her 16-year-old classmate was arrested on suspicion of homicide. One and a half months before the murder, a psychiatrist who had been examining the girl called a prefectural child consultation centre to warn that she might commit murder, but he did not reveal her name, considering it his professional duty to keep it confidential. Article 134 of the Japanese Criminal Law states that doctors should not disclose patient information obtained in clinical practice without a legitimate reason, but the Japanese Supreme Court has not specified what constitutes a legitimate reason. Mass media and commentators suggested that the murder could have been prevented if the psychiatrist had disclosed the girl's name to the authorities or had isolated her coercively in a psychiatric ward. However, the authors disagree with such claims. This article discusses obligations imposed on concerned individuals and third party members in cases involving ethical dilemmas regarding patient confidentiality and information disclosure. It is concluded that everyone should fulfill their obligations to prevent such tragedies and one should judge the appropriateness of others' actions based not on the consequences of their actions, but on the processes used to decide on a course of action and their commitment. It is necessary for us to establish a society in which concerned parties can do what they think is ethically best without fearing ungrounded charges. PMID- 26833627 TI - Streptomyces coelicolor XdhR is a direct target of (p)ppGpp that controls expression of genes encoding xanthine dehydrogenase to promote purine salvage. AB - The gene encoding Streptomyces coelicolor xanthine dehydrogenase regulator (XdhR) is divergently oriented from xdhABC, which encodes xanthine dehydrogenase (Xdh). Xdh is required for purine salvage pathways. XdhR was previously shown to repress xdhABC expression. We show that XdhR binds the xdhABC-xdhR intergenic region with high affinity (Kd ~ 0.5 nM). DNaseI footprinting reveals that this complex formation corresponds to XdhR binding the xdhR gene promoter at two adjacent sites; at higher protein concentrations, protection expands to a region that overlaps the transcriptional and translational start sites of xdhABC. While substrates for Xdh have little effect on DNA binding, GTP and ppGpp dissociate the DNA-XdhR complex. Progression of cells to stationary phase, a condition associated with increased (p)ppGpp production, leads to elevated xdhB expression; in contrast, inhibition of Xdh by allopurinol results in xdhB repression. We propose that XdhR is a direct target of (p)ppGpp, and that expression of xdhABC is upregulated during the stringent response to promote purine salvage pathways, maintain GTP homeostasis and ensure continued (p)ppGpp synthesis. During exponential phase growth, basal levels of xdhABC expression may be achieved by GTP serving as a lower-affinity XdhR ligand. PMID- 26833628 TI - Modifications of the cell wall of yeasts grown on hexadecane and under starvation conditions. AB - Electron-microscopic examinations have demonstrated local modifications in the cell wall of the yeast Candida maltosa grown on hexadecane. In our earlier studies, these modified sites, observed in other yeasts grown on oil hydrocarbons, were conventionally called 'canals'. The biochemical and cytochemical studies of C. maltosa have revealed a correlation between the formation of 'canals' and decrease in the amount of cell wall polysaccharides, glucan and mannan. The ultrathin sections and surface replicas have shown that the 'canals' are destroyed by pronase, thus indicating that a significant proportion of their content is represented by proteins. This finding was compatible with our earlier data on the localization of oxidative enzymes in 'canals' and possible participation of the 'canals' in the primary oxidation of hydrocarbons. A completely unexpected and intriguing phenomenon has been the appearance of 'canals' in the yeast C. maltosa under starvation conditions. Unlike the yeasts grown on hexadecane, mannan almost disappears in starving cells, while the quantity of glucan first decreases and then is restored to its initial level. The role of 'canals' in starving cells is as yet unclear; it is assumed that they acquire exoenzymes involved in the utilization of products of cell lysis in the starving population. In the future, 'canals' of starving cells will be studied in connection with their possible participation in apoptosis. PMID- 26833629 TI - Crystal Organic Light-Emitting Diodes with Perfectly Oriented Non-Doped Pt-Based Emitting Layer. AB - Organic light-emitting diodes with external quantum efficiency of 38.8% are realized using a Pt-based thin-film emitting layer with photoluminescence quantum yield of 96% and transition dipole ratio of 93%. The emitting dipole orientation of the thin films fabricated using Pt complexes is investigated and the structural relationship between X-ray structural analysis and the structures in thin films are discussed based on quantum chemical calculations. PMID- 26833630 TI - Regioselective Synthesis of Quinazolinone-/Phenanthridine-Fused Heteropolycycles by Pd-Catalyzed Direct Intramolecular Aerobic Oxidative C-H Amination from Aromatic Strained Amides. AB - A new route for the expedient synthesis of specific regioisomer of quinazolinone- and phenanthridine-fused heterocycles through a palladium-catalyzed regioselective intramolecular oxidative C-H amination from cyclic strained amides of aromatic amido-amidine systems (quinazolinones) has been developed. The amine functionalization of an aromatic C-H bond from a strained amide nitrogen involved in aromaticity has been a challenging work so far. The fusion of two heterocyclic cores, quinazolinone and phenanthridine, can occur in two different ways (linear and angular), but under the conditions reported here, only linear type isomer is exclusively produced. This approach provides a variety of substituted quinazolinone- and phenanthridine-fused derivatives in moderate to excellent yields. Moreover, such fused molecules show excellent fluorescent properties and have great potential to be a new type of fluorophores for the use in medicinal and material science. PMID- 26833631 TI - 2D Confined-Space Assisted Growth of Molecular-Level-Thick Polypyrrole Sheets with High Conductivity and Transparency. AB - Herein, the use of a 2D soft template system composed of hundred-nanometer-thick water/ethanol mixed layers sandwiched by lamellar bilayer membranes of a self assembled amphiphilic molecule to produce ultrathin polyprrole (PPy) with a uniform thickness as thin as 3.8 nm and with large dimensions (>2 MUm(2)) is presented. The obtained PPy nanosheets exhibit regioregularity with ordered chain alignment where the polymer chains in the nanosheets produced are well aligned with a clear interchain spacing as confirmed by small-angle X-ray scattering measurement. The molecular-level-thick PPy nanosheets exhibit extremely high conductivity up to 1330 S m(-1), thanks to the ordered alignment of polymer chains in the nanosheets, and a high transparency in both the visible region (transmittance >99%) and near-infrared region (transmittance >93%). PMID- 26833632 TI - Natural killer cells in highly exposed hepatitis C-seronegative injecting drug users. AB - Injecting drug use remains the major risk factor for hepatitis C (HCV) transmission. A minority of long-term injecting drug users remain seronegative and aviraemic, despite prolonged exposure to HCV - termed highly exposed seronegative subjects. Natural killer (NK) cells have been implicated in this apparent protection. A longitudinal nested, three group case-control series of subjects was selected from a prospective cohort of seronegative injecting drug users who became incident cases (n = 11), remained seronegative (n = 11) or reported transient high-risk behaviour and remained uninfected (n = 11). The groups were matched by age, sex and initial risk behaviour characteristics. Stored peripheral blood mononuclear cells were assayed in multicolour flow cytometry to enumerate natural killer cell subpopulations and to assess functional activity using Toll-like receptor ligands before measurement of activation, cytokine production and natural cytotoxicity receptor expression. Principal components were derived to describe the detailed phenotypic characteristics of the major NK subpopulations (based on CD56 and CD16 co expression), before logistic regression analysis to identify associations with exposed, seronegative individuals. The CD56(dim) CD16(+) (P = 0.05, OR 6.92) and CD56(dim) CD16(-) (P = 0.05, OR 6.07) principal components differed between exposed, seronegative individuals and pre-infection samples of the other two groups. These included CD56(dim) CD16(+) and CD56(dim) CD16(-) subsets with CD56(dim) CD16(+) IFN-gamma and TNF-alpha on unstimulated cells, and CD56(dim) CD16(-) CD69(+) , CD107a(+) , IFN-gamma and TNF-alpha following TLR stimulation. The cytotoxic CD56(dim) NK subset thus distinguished highly exposed, seronegative subjects, suggesting NK cytotoxicity may contribute to protection from HCV acquisition. Further investigation of the determinants of this association and prospective assessment of protection against HCV infection are warranted. PMID- 26833633 TI - Aversion learning can reduce meal size without taste avoidance in rats. AB - OBJECTIVE: Nausea and aversive food responses are commonly reported following bariatric surgery, along with post-surgical reduction in meal size. This study investigates whether a meal size limit can be conditioned by associating large meals with aversive outcomes. METHODS: In rats, the intake of meals exceeding a pre-defined size threshold was paired with lithium chloride-induced gastric illness, and the effects on self-determined food intakes and body weight were measured. RESULTS: Rats given LiCl contingent on the intake of a large meal learned to reliably reduce intake below this meal size threshold, while post-meal saline or LiCl before meals did not change meal size. It was further demonstrated that this is not a conditioned taste aversion and that this effect transferred to foods not explicitly trained. Finally, when rats received LiCl following all large meals, the number of small meals increased, but total food intake and body weight decreased. CONCLUSIONS: While further work is needed, this is the first demonstration that meal size may be conditioned, using an aversion procedure, to remain under a target threshold and that this effect is distinct from taste avoidance. Corresponding reduction in food intake and body weight suggests that this phenomenon may have implications for developing weight loss strategies and understanding the efficacy of bariatric surgery. PMID- 26833634 TI - Persistent Vascular Remodeling and Leakiness are Important Components of the Pathobiology of Re-bleeding in Hemophilic Joints: Two Informative Cases. AB - OBJECTIVE: It is unclear if vascular remodeling in hemophilic joints perpetuates bleeding because it is difficult to gauge leakiness in the setting of low clotting factor levels. Two patients provided the unique opportunity to demonstrate that vascular changes directly contribute to joint bleeding. APPROACH AND RESULTS: Two patients had severe hemophilic arthropathies; joint vascularity and bleeding were studied during periods of normalized plasma clotting factor activities with MSKUS and PD. One patient was "cured" of hemophilia with liver transplantation. Abnormal elbow vascularization persisted despite normalization of coagulation status and was associated with severe bleeding years after transplant. Dynamic vascular changes were detected prior to and during bleeding; angiography revealed enlarged, thickened vessels consistent with remodeling, and required arterial embolization. The second patient had continued knee bleeding and fluctuating vascular changes for months following knee replacement, unresponsive to intense daily factor treatment. Subsequently, new bleeds developed in other joints associated with similar vascular changes despite continued factor replacement. CONCLUSIONS: Vascular remodeling contributes to perpetuated hemophilic joint bleeding and therefore contributes to progressive arthropathy. Intra-articular or systemic administration of anti-angiogenic drugs, such as vascular endothelial growth factor antagonists, might be of benefit in such patients, but requires study. PMID- 26833635 TI - Umpolung Reactions of alpha-Imino Esters: Useful Methods for the Preparation of alpha-Amino Acid Frameworks. AB - This paper summarizes our recent efforts toward the development of tandem reactions utilizing umpolung reactions of alpha-imino esters. A highly diastereoselective tandem N-alkylation-Mannich reaction of alpha-imino esters was developed. A tandem N-alkylation-addition reaction of alpha-imino esters derived from ethyl glyoxylate with various aldehydes proceeded to give 1,2-amino alcohols. The same reaction also proceeded efficiently using a novel flow system comprising two connected microreactors. Novel syntheses of alpha-quaternary alkynyl amino esters and allenoates were developed through the use of umpolung N addition to beta,gamma-alkynyl alpha-imino esters, followed by regioselective acylation. In addition, a highly regioselective tandem N-alkylation-vinylogous aldol reaction of beta,gamma-alkenyl alpha-imino esters was discovered. N Alkylation of alpha-iminophosphonates followed by a Horner-Wadsworth-Emmons reaction with aldehydes occurred to afford enamines, which can be used in a four component coupling reaction with methyl vinyl ketone. alpha-N-Acyloxyimino esters served as highly efficient substrates for the N,N,C-trialkylation reaction to introduce various nucleophiles at the imino nitrogen and carbon atoms. PMID- 26833636 TI - Cell-free DNA testing for 22q11.2 deletion syndrome: appraising the viability, effectiveness and appropriateness of screening. PMID- 26833637 TI - Re: Review of the correlation between blood flow velocity and polycythemia in the fetus, neonate and adult: appropriate diagnostic levels need to be determined for twin anemia-polycythemia sequence. A. Lucewicz, K. Fisher, A.Henry and A. W. Welsh. Ultrasound Obstet Gynecol 2016; 47: 152-157. PMID- 26833638 TI - Re: Prenatal ultrasound evaluation of segmental level of neurological lesion in fetuses with myelomeningocele: development of a new technique. E.Carreras, A. Maroto, T. Illescas, M. Melendez, S. Arevalo, J. L. Peiro, C. G. Garcia-Fontecha, M. Belfort and A. Cuxart. Ultrasound Obstet Gynecol 2016; 47: 162-167. PMID- 26833639 TI - The effect of zinc deficiency on salt taste acuity, preference, and dietary sodium intake in hemodialysis patients. AB - Introduction High sodium intake is the main cause of fluid overload in hemodialysis (HD) patients, leading to increased cardiovascular mortality. High sodium intake is known to be associated with low salt taste acuity and/or high preference. As the zinc status could influence taste acuity, we analyzed the effect of zinc deficiency on salt taste acuity, preference, and dietary sodium intake in HD patients. Methods A total of 77 HD patients was enrolled in this cross-sectional study. Zinc deficiency was defined as serum zinc level with below 70 ug/mL. The patients were divided into two groups based on serum zinc level. Salt taste acuity and preference were determined by a sensory test using varying concentrations of NaCl solution, and dietary sodium intake was estimated using 3 day dietary recall surveys. Findings The mean salt recognition threshold and salt taste preference were significantly higher in the zinc deficient group than in the non-zinc deficient group. And there was significant positive correlation between salt taste preference and dietary sodium intake in zinc deficient group (r = 0.43, P = 0.002). Although, the dietary sodium intake showed a high tendency with no significance (P = 0.052), interdialytic weight gain was significantly higher in the zinc deficient group than in the non-zinc deficient group (2.68 +/- 1.02 kg vs. 3.18 +/- 1.02 kg; P = 0.047). Discussion Zinc deficiency may be related to low salt taste acuity and high salt preference, leading to high dietary sodium intake in HD patients. PMID- 26833640 TI - Exploiting the Multidentate Nature of Chiral Disulfonimides in a Multicomponent Reaction for the Asymmetric Synthesis of Pyrrolo[1,2-a]indoles: A Remarkable Case of Enantioinversion. AB - A new multicomponent coupling reaction for the enantioselective synthesis of pyrrolo[1,2-a]indoles under the catalysis of a chiral disulfonimide is described. The high specificity of the reaction is a consequence of the multidentate character of the Bronsted acid catalyst. Insights from DFT calculations helped explain the unexpected high enantioselectivity observed with the simplest 3,3' unsubstituted binaphthyl catalyst as a result of transition-state stabilization by a network of cooperative noncovalent interactions. The remarkable enantioinversion resulting from the simple introduction of substituents at 3- and 3'-positions, the first reported example of this phenomenon in the context of binaphthalene-derived Bronsted acid catalysis, was instead attributed to destabilizing steric interactions. PMID- 26833641 TI - What is the viva experience of phase 2 Radiation Oncology examination candidates? Survey and advice for future candidates. AB - INTRODUCTION: Medical speciality examination is a very stressful event in medical careers. We aimed to determine the subjective experience of Radiation Oncology Royal Australian and New Zealand College of Radiologists (RANZCR) oral examination candidates. It was hoped the results would provide reassurance and advice for future candidates. METHODS: We distributed an anonymous online survey through the RANZCR membership database to Radiation Oncology Trainees and fellows who may have sat their oral examination within the last 3 years. RESULTS: There were 21 responses, yielding a response rate of 21%. Nineteen percent of respondents were moderately or very surprised during their viva and the most frequently noted cause was the demeanour of the examiners. The clinical cases and clinical examination station were rated very fair by over 80% of responders while the planning cases were rated very fair by 57%. During the viva, 33% thought they passed and 71% of these candidates were successful. Forty-three percent felt they were borderline, and all of these respondents passed. Five participants (24%) failed in the first attempt and four described being unable to convey their actual knowledge. Candidates found mock examinations to be the most useful examination preparation activity. The most frequently given advice was to focus on the planning examination. CONCLUSIONS: The majority of this select group of candidates indicated that the oral examination cases were very fair. Candidates rated the planning exam as least fair, indicating this may be the area that would benefit most from better preparation. PMID- 26833643 TI - A bacterial hydrogen-dependent CO2 reductase forms filamentous structures. AB - Interconversion of CO2 and formic acid is an important reaction in bacteria. A novel enzyme complex that directly utilizes molecular hydrogen as electron donor for the reversible reduction of CO2 has recently been identified in the Wood Ljungdahl pathway of an acetogenic bacterium. This pathway is utilized for carbon fixation as well as energy conservation. Here we describe the further characterization of the quaternary structure of this enzyme complex and the unexpected behavior of this enzyme in polymerizing into filamentous structures. Polymerization of metabolic enzymes into similar structures has been observed only in rare cases but the increasing number of examples point towards a more general characteristic of enzyme functioning. Polymerization of the purified enzyme into ordered filaments of more than 0.1 MUm in length was only dependent on the presence of divalent cations. Polymerization was a reversible process and connected to the enzymatic activity of the oxygen-sensitive enzyme with the filamentous form being the most active state. PMID- 26833642 TI - Aspirin does not reduce the clinical benefits of the mineralocorticoid receptor antagonist eplerenone in patients with systolic heart failure and mild symptoms: an analysis of the EMPHASIS-HF study. AB - AIMS: It is not known whether concomitant use of aspirin might attenuate the beneficial effects of mineralocorticoid receptor antagonists (MRAs). The purpose of this subgroup analysis was to explore the interaction between baseline aspirin treatment and the effect of eplerenone on the primary efficacy outcomes (composite of hospitalization for heart failure or cardiovascular mortality), its components, and safety markers [estimated glomerular filtration rate (eGFR), systolic blood pressure (SBP), and serum potassium >5.5 mmol/L] in the Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure trial (EMPHASIS-HF). METHODS AND RESULTS: Patients with chronic heart failure, reduced ejection fraction (HFREF), and mild symptoms were enrolled in EMPHASIS-HF. We evaluated baseline characteristics according to aspirin use. We explored the interaction between aspirin and eplerenone, using Cox proportional hazards models providing adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) and P values for interaction. Of the 2737 patients randomized, 1605 patients (58.6%) were taking aspirin. The beneficial effects of eplerenone on the primary endpoint were similar in patients not treated (adjusted HR 0.59, 95% CI 0.46-0.75) or treated (adjusted HR 0.71, 95% CI 0.59-0.87) with aspirin at baseline (interaction P-value = 0.19). We did not observe any significant modification of the safety markers by aspirin that was clinically meaningful. CONCLUSION: Aspirin use in patients with chronic systolic heart failure and mild symptoms did not substantially reduce the overall beneficial effects of the MRA eplerenone contrary to what has been described in some studies with ACE inhibitors. PMID- 26833644 TI - Highlights from the Current Issue: February 2016. PMID- 26833645 TI - Clinical Practice Guideline: Otitis Media with Effusion Executive Summary (Update). AB - The American Academy of Otolaryngology-Head and Neck Surgery Foundation has published a supplement to this issue of Otolaryngology-Head and Neck Surgery featuring the updated "Clinical Practice Guideline: Otitis Media with Effusion." To assist in implementing the guideline recommendations, this article summarizes the rationale, purpose, and key action statements. The 18 recommendations developed emphasize diagnostic accuracy, identification of children who are most susceptible to developmental sequelae from otitis media with effusion, and education of clinicians and patients regarding the favorable natural history of most otitis media with effusion and the lack of efficacy for medical therapy (eg, steroids, antihistamines, decongestants). An updated guideline is needed due to new clinical trials, new systematic reviews, and the lack of consumer participation in the initial guideline development group. PMID- 26833647 TI - Parathyroid Surgery: Getting It Right the First Time. PMID- 26833646 TI - Plain Language Summary: Otitis Media with Effusion. AB - OBJECTIVE: This plain language summary serves as an overview in explaining otitis media with effusion (pronounced Oh-TIE-tis ME-dee-uh with Ef-YOO-zhun), abbreviated "OME" and often called "ear fluid." The summary applies to children aged 2 months through 12 years with OME and is based on the 2015 "Clinical Practice Guideline: Otitis Media with Effusion (Update)." The evidence-based guideline includes research to support more effective diagnosis and treatment of OME in children. The guideline was developed as a quality improvement opportunity for managing OME by creating clear recommendations to use in medical practice. PMID- 26833648 TI - Response to "Parathyroid Surgery: Getting It Right the First Time": Parathyroid Surgery: Primum Non Nocere. PMID- 26833649 TI - A Beacon of Emotional Resilience in a Storm of Mistreatment? PMID- 26833650 TI - Response to "A Beacon of Emotional Resilience in a Storm of Mistreatment?". PMID- 26833651 TI - Corrigendum. AB - Thompson GP, Sladen DP, Hughes Borst BJ, Still OL. Accuracy of a tablet audiometer for measuring behavioral hearing thresholds in a clinical population. Otolaryngol Head Neck Surg. 2015;153:838-842. (Original DOI: 10.1177/0194599815593737). PMID- 26833656 TI - Sentient Nonpersons and the Disvalue of Death. AB - Implicit in our everyday attitudes and practices is the assumption that death ordinarily harms a person who dies. A far more contested matter is whether death harms sentient individuals who are not persons, a category that includes many animals and some human beings. On the basis of the deprivation account of the harm of death, I argue that death harms sentient nonpersons (whenever their lives would be worth continuing). I next consider possible bases for the commonsense judgment that death ordinarily harms persons more than it harms sentient nonpersons. Contrary to what some philosophers believe, it is doubtful that the familiar resources of prudential value theory can vindicate this judgment. I show that the approach that at first glance seems most promising for supporting this judgment - namely, invoking an objective account of well-being - faces substantial challenges, before arguing that McMahan's time-relative interest account supplies the needed theoretical basis. I then go on to extract a significant practical implication of the first thesis, that death ordinarily harms sentient nonpersons: We should find a way to discontinue the routine killing of animal subjects following their use in experiments. PMID- 26833657 TI - The Impact of Alemtuzumab and Basiliximab Induction on Patient Survival and Time to Bronchiolitis Obliterans Syndrome in Double Lung Transplantation Recipients. AB - We examined the effect of alemtuzumab and basiliximab induction therapy on patient survival and freedom from bronchiolitis obliterans syndrome (BOS) in double lung transplantation. The United Network for Organ Sharing database was reviewed for adult double lung transplant recipients from 2006 to 2013. The primary outcome was risk-adjusted all-cause mortality. Secondary outcomes included time to BOS. There were 6117 patients were identified, of whom 738 received alemtuzumab, 2804 received basiliximab, and 2575 received no induction. Alemtuzumab recipients had higher lung allocation scores compared with basiliximab and no-induction recipients (41.4 versus 37.9 versus 40.7, p < 0.001) and were more likely to require mechanical ventilation before to transplantation (21.7% versus 6.5% versus 6.2%, p < 0.001). Median survival was longer for alemtuzumab and basiliximab recipients compared with patients who received no induction (2321 versus 2352 versus 1967 days, p = 0.001). Alemtuzumab (hazard ratio 0.80, 95% confidence interval 0.67-0.95, p = 0.009) and basiliximab induction (0.88, 0.80-0.98, p = 0.015) were independently associated with survival on multivariate analysis. At 5 years, alemtuzumab recipients had a lower incidence of BOS (22.7% versus 55.4 versus 55.9%), and its use was independently associated with lower risk of developing BOS on multivariate analysis. While both induction therapies were associated with improved survival, patients who received alemtuzumab had greater median freedom from BOS. PMID- 26833658 TI - Potential of zebrafish as a model for exploring the role of the amygdala in emotional memory and motivational behavior. AB - Emotion is a key aspect of behavior, enabling humans and animals to assign either positive or negative values to sensory inputs and thereby to make appropriate decisions. Classical experiments in mammalian models, mainly in primates and rodents, have shown that the amygdala is essential for appetitive and aversive associative processing and that dysfunction of this brain region leads to various psychiatric conditions, including depression, generalized anxiety disorder, panic disorder, phobias, autism, and posttraumatic stress disorder. In the past 2 decades, the zebrafish (Danio rerio; Cyprinidae) has emerged as a versatile, reliable vertebrate model organism for the in vivo study of development, gene function, and numerous aspects of human pathologies. Small size, high fecundity, rapid external development, transparency, genetic tractability, and high genetic and physiologic homology with humans are among the factors that have contributed to the success with this small fish in different biomedical research areas. Recent findings indicate that, despite the anatomical differences in the brain structure of teleosts and tetrapods, fish possess a structure homologous to the mammalian amygdala, a hypothesis that is supported by the expression of molecular markers, analyses of neuronal projections in different brain areas, and behavioral studies. This Review summarizes this evidence and highlights a number of relevant bioassays in zebrafish to study emotional memory and motivational behavior. PMID- 26833659 TI - The post-transcriptional regulatory system CSR controls the balance of metabolic pools in upper glycolysis of Escherichia coli. AB - Metabolic control in Escherichia coli is a complex process involving multilevel regulatory systems but the involvement of post-transcriptional regulation is uncertain. The post-transcriptional factor CsrA is stated as being the only regulator essential for the use of glycolytic substrates. A dozen enzymes in the central carbon metabolism (CCM) have been reported as potentially controlled by CsrA, but its impact on the CCM functioning has not been demonstrated. Here, a multiscale analysis was performed in a wild-type strain and its isogenic mutant attenuated for CsrA (including growth parameters, gene expression levels, metabolite pools, abundance of enzymes and fluxes). Data integration and regulation analysis showed a coordinated control of the expression of glycolytic enzymes. This also revealed the imbalance of metabolite pools in the csrA mutant upper glycolysis, before the phosphofructokinase PfkA step. This imbalance is associated with a glucose-phosphate stress. Restoring PfkA activity in the csrA mutant strain suppressed this stress and increased the mutant growth rate on glucose. Thus, the carbon storage regulator system is essential for the effective functioning of the upper glycolysis mainly through its control of PfkA. This work demonstrates the pivotal role of post-transcriptional regulation to shape the carbon metabolism. PMID- 26833663 TI - Fat, Calories, and Cancer. PMID- 26833660 TI - Office-based olfactory mucosa biopsies. AB - BACKGROUND: Requests from researchers for olfactory mucosal biopsies are increasing as a result of advances in the fields of neuroscience and stem cell biology. Published studies report variable rates of success in obtaining true olfactory tissue, often below 50%. In cases where biopsies are not obtained carefully and confirmed through histological techniques, erroneous conclusions are made. Attention to the epithelium alone without submucosal analysis may add to the confusion. A consistent biopsy technique can help rhinologists obtain higher yields of olfactory mucosa. Confirmatory tissue staining analysis assures olfactory mucosa has been obtained, thereby strengthening clinical correlations and scientific conclusions. METHODS: Biopsies of the septum within the anterior olfactory cleft were obtained under endoscopic guidance in an office procedure room using topical local anesthetic (lidocaine). After mucosal incision, a small, cupped, biopsy forceps was used to obtain specimens approximately 2 to 3 mm in size. Specimens were sectioned and analyzed with immunohistochemistry for presence of olfactory epithelium and/or olfactory fascicles. RESULTS: A total of 14 subjects were biopsied in this analysis. Four subjects had biopsies in the operating room (OR). The remaining 10 underwent biopsies in the clinic. All biopsies obtained in the OR revealed evidence of olfactory mucosa. Of the 10 clinic biopsies, 8 (80%) revealed evidence of olfactory mucosa. No complications were encountered. CONCLUSION: High yields of olfactory mucosa can be obtained safely in an office-based setting. Technique, including attention to the area of biopsy, and confirmatory analysis are important in assuring presence of olfactory tissue. PMID- 26833661 TI - Partial purification of histone H3 proteolytic activity from the budding yeast Saccharomyces cerevisiae. AB - The proteolytic clipping of histone tails has recently emerged as a novel form of irreversible post-translational modification (PTM) of histones. Histone clipping has been implicated as a regulatory process leading to the permanent removal of PTMs from histone proteins. However, there is scarcity of literature that describes the identification and characterization of histone-specific proteases. Here, we employed various biochemical methods to report histone H3-specific proteolytic activity from budding yeast. Our results demonstrate that H3 proteolytic activity was associated with sepharose bead matrices and activity was not affected by a variety of stress conditions. We have also identified the existence of an unknown protein that acts as a physiological inhibitor of the H3 clipping activity of yeast H3 protease. Moreover, through protease inhibition assays, we have also characterized yeast H3 protease as a serine protease. Interestingly, unlike glutamate dehydrogenase (GDH), yeast H3 proteolytic activity was not inhibited by Stefin B. Together, our findings suggest the existence of a novel H3 protease in yeast that is different from other reported histone H3 proteases. The presence of histone H3 proteolytic activity, along with the physiological inhibitor in yeast, suggests an interesting molecular mechanism that regulates the activity of histone proteases. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833664 TI - Observations on Radiation-Induced Lymphoid Tumors of Mice. PMID- 26833666 TI - Correction: Development of a New Tracking Tool for the Human Monomeric Laminin gamma2 Chain In Vitro and In Vivo. PMID- 26833665 TI - Systemic Chromosome Instability Resulted in Colonic Transcriptomic Changes in Metabolic, Proliferation, and Stem Cell Regulators in Sgo1-/+ Mice. AB - Colon cancer is the second most lethal cancer and is predicted to claim 49,700 lives in the United States this year. Chromosome instability (CIN) is observed in 80% to 90% of colon cancers and is thought to contribute to colon cancer progression and recurrence. To investigate the impact of CIN on colon cancer development, we developed shugoshin-1 (Sgo1) haploinsufficient (-/+) mice, an animal model focusing on mitotic error-induced CIN. In this study, we analyzed signature changes in the colonic transcriptome of Sgo1(-/+) mice to examine the molecular events underlying the altered carcinogenesis profiles in Sgo1(-/+) mice. We performed next-generation sequencing of normal-looking colonic mucosal tissue from mice treated with the carcinogen azoxymethane after 24 weeks. Transcriptome profiling revealed 349 hits with a 2-fold expression difference threshold (217 upregulated genes, 132 downregulated genes, P < 0.05). Pathway analyses indicated that the Sgo1-CIN tissues upregulated pathways known to be activated in colon cancer, including lipid metabolism (z score 4.47), Notch signaling (4.47), insulin signaling (3.81), and PPAR pathways (3.75), and downregulated pathways involved in immune responses including allograft rejection (6.69) and graft-versus-host disease (6.54). Notably, stem cell markers were also misregulated. Collectively, our findings demonstrate that systemic CIN results in transcriptomic changes in metabolism, proliferation, cell fate, and immune responses in the colon, which may foster a microenvironment amenable to cancer development. Therefore, therapeutic approaches focusing on these identified pathways may be valuable for colon cancer prevention and treatment. PMID- 26833667 TI - Visible-Frequency Metasurface for Structuring and Spatially Multiplexing Optical Vortices. AB - A multifocus optical vortex metalens, with enhanced signal-to-noise ratio, is presented, which focuses three longitudinal vortices with distinct topological charges at different focal planes. The design largely extends the flexibility of tuning the number of vortices and their focal positions for circularly polarized light in a compact device, which provides the convenience for the nanomanipulation of optical vortices. PMID- 26833668 TI - How can the physician safely proceed with the human machine? PMID- 26833669 TI - A systematic review of electronic multi-compartment medication devices with reminder systems for improving adherence to self-administered medications. AB - BACKGROUND: Many patients experience difficulties adhering to medication regimes. For people who forget or get confused about medication, there are products to help them such as multi-compartment medication devices (MMDs). Some of these, known as electronic MMDs (eMMDs), use audible and/or visual signals to prompt the patient when to take medication, dispense medications, give instructions to the patient, and contact a caregiver (mobile Internet or text to a carer) as needed. AIM: To systematically review the literature on the use of eMMDs, to determine what evidence for their effectiveness is available. METHODS: A comprehensive literature search of 10 databases, plus an Internet search and hand searching was conducted, using the MeSH terms reminder systems/patient compliance/medication adherence. There were no date restrictions. Inclusion criteria were patients in any community setting, in any country and with no restrictions of age, gender, ethnicity or medical condition, using an eMMD. Peer-reviewed quantitative or qualitative studies of any design were included. RESULTS: Of 805 abstracts identified and 99 full text papers retrieved, six met the inclusion criteria. Five of the studies reported adherence to medication regimes; one reported design factors to improve adherence. Adherence varied by the context of the reminders, the target group and usability of the devices. The studies were small scale and only one was a well conducted randomised controlled trial. CONCLUSION: Overall methodological quality of the studies was poor. Although positive effects on adherence were reported further, rigorously conducted, studies are needed to inform the use of eMMDs. PMID- 26833670 TI - 2H-Tetrakis(3,5-di-tert-butyl)phenylporphyrin on a Cu(110) Surface: Room Temperature Self-Metalation and Surface-Reconstruction-Facilitated Self-Assembly. AB - The adsorption behavior of 2H-tetrakis(3,5-di-tert-butyl)phenylporphyrin (2HTTBPP) on Cu(110) and Cu(110)-(2*1)O surfaces have been investigated by using variable-temperature scanning tunneling microscopy (STM) under ultrahigh vacuum conditions. On the bare Cu(110) surface, individual 2HTTBPP molecules are observed. These molecules are immobilized on the surface with a particular orientation with respect to the crystallographic directions of the Cu(110) surface and do not form supramolecular aggregates up to full monolayer coverage. In contrast, a chiral supramolecular structure is formed on the Cu(110)-(2*1)O surface, which is stabilized by van der Waals interactions between the tert-butyl groups of neighboring molecules. These findings are explained by weakened molecule-substrate interactions on the Cu(110)-(2*1)O surface relative to the bare Cu(110) surface. By comparison with the corresponding results of Cu tetrakis(3,5-di-tert-butyl)phenylporphyrin (CuTTBPP) on Cu(110) and Cu(110) (2*1)O surfaces, we find that the 2HTTBPP molecules can self-metalate on both surfaces with copper atoms from the substrate at room temperature (RT). The possible origins of the self-metalation reaction at RT are discussed. Finally, peculiar irreversible temperature-dependent switching of the intramolecular conformations of the investigated molecules on the Cu(110) surface was observed and interpreted. PMID- 26833671 TI - Grassland responses to increased rainfall depend on the timescale of forcing. AB - Forecasting impacts of future climate change is an important challenge to biologists, both for understanding the consequences of different emissions trajectories and for developing adaptation measures that will minimize biodiversity loss. Existing variation provides a window into the effects of climate on species and ecosystems, but in many places does not encompass the levels or timeframes of forcing expected under directional climatic change. Experiments help us to fill in these uncertainties, simulating directional shifts to examine outcomes of new levels and sustained changes in conditions. Here, we explore the translation between short-term responses to climate variability and longer-term trajectories that emerge under directional climatic change. In a decade-long experiment, we compare effects of short-term and long-term forcings across three trophic levels in grassland plots subjected to natural and experimental variation in precipitation. For some biological responses (plant productivity), responses to long-term extension of the rainy season were consistent with short-term responses, while for others (plant species richness, abundance of invertebrate herbivores and predators), there was pronounced divergence of long-term trajectories from short-term responses. These differences between biological responses mean that sustained directional changes in climate can restructure ecological relationships characterizing a system. Importantly, a positive relationship between plant diversity and productivity turned negative under one scenario of climate change, with a similar change in the relationship between plant productivity and consumer biomass. Inferences from experiments such as this form an important part of wider efforts to understand the complexities of climate change responses. PMID- 26833672 TI - Sporting injuries, seasonal trend and impact on rural Australian hospitals: Implications and recommendations. AB - OBJECTIVES: To determine the prevalence of sporting injuries in a regional Australian setting and readiness of the rural health systems to combat the overall impact. DESIGN, SETTING AND PARTICIPANTS: Five years of data between 2008 and 2012 from the Victorian Emergency Minimal Dataset showing sports injuries presenting to Goulburn Valley Base Hospital Emergency Department (ED) were analysed. MAIN OUTCOME MEASURES: Prevalence of overall sporting injuries including different types and location of injury in the body, seasonal variation for emergency presentation, mechanism of injury and hospital admissions. RESULTS: We observed a total of 4537 Emergency presentations and 235 hospitalisations between 2008 and 2012 with sporting injuries. About 78% of injuries presented in the winter sporting months; the rate of injury was higher in the month of 'May' across the most data reviewing years. Also, there was a higher proportion of hospital admissions recorded in winter sporting months. We reported that those who played sports in winter were significantly younger than those in summer (P < 0.05). Sprains and strains due to different sporting activities were the commonest cause of ED presentations, while falls and collisions were the mostly reported mechanism for sporting injuries. CONCLUSION: It might be extrapolated from the data that within a regional setting, there is a need to optimise emergency departments and hospital bed availability with emphasis on orthopaedic involvements during the winter sporting months. Many of these sports injuries are preventable and community risk reduction strategies should be applied to reduce the burden to the regional hospitals. PMID- 26833673 TI - Cardiopulmonary Exercise Testing as a Tool for Diagnosing Pulmonary Hypertension in Patients with Dilated Cardiomyopathy. AB - BACKGROUND: Recently, it has become increasingly recognized that pulmonary hypertension (PH) is a particularly threatening result of left-sided heart disease. However, there have been few investigations of the impact of cardiopulmonary exercise testing (CPX) variables on PH in dilated cardiomyopathy (DCM). We evaluated the usefulness of crucial CPX variables for detecting elevated pulmonary arterial pressure (PAP) in patients with DCM. METHODS: Ninety subjects with DCM underwent cardiac catheterization and CPX at our hospital. Receiver operator characteristic (ROC) analysis was performed to assess the ability of CPX variables to distinguish between the presence and absence of PH. RESULTS: Overall mean values were: mean PAP (mPAP), 18.0 +/- 9.6 mmHg; plasma brain natriuretic peptide, 233 +/- 295 pg/mL; and left ventricular ejection fraction, 30.2 +/- 11.0%. Patients were allocated to one of two groups on the basis of mean PAP, namely DCM without PH [mean PAP (mPAP) <25 mmHg; n = 75] and DCM with PH (mPAP >=25 mmHg; n = 15). A cutoff achieved percentage of predicted peak VO2 (%PPeak VO2 ) of 52.5% was the best predictor of an mPAP >=25 mmHg in the ROC analysis (area under curve: 0.911). In the multivariate analysis, %PPeak VO2 was the only significant independent predictor of PH (Wald 6.52, odds ratio 0.892, 95% CI 0.818-0.974; P = 0.011). CONCLUSIONS: %PPeak VO2 was strongly associated with the presence of PH in patients with DCM. Taken together, these findings indicate that CPX variables could be important for diagnosing PH in patients with DCM. PMID- 26833674 TI - Use of mammalian target of rapamycin inhibitors after failure of tyrosine kinase inhibitors in patients with metastatic renal cell carcinoma undergoing hemodialysis: A single-center experience with four cases. AB - We retrospectively identified patients with end-stage renal disease undergoing hemodialysis treated with the mammalian target of rapamycin inhibitors as a second- and/or third-line targeted therapy after treatment failure with the tyrosine kinase inhibitors for metastatic renal cell carcinoma. Patient medical records were reviewed to evaluate the response to therapies and treatment-related toxicities. Four patients were identified. All patients had undergone nephrectomy, and one had received immunotherapy before targeted therapy. Two patients had clear cell histology, and the other two had papillary histology. All patients were classified into the intermediate risk group according to the Memorial Sloan-Kettering Cancer Center risk model. All patients were treated with everolimus as a second- or third-line therapy, and two patients were treated with temsirolimus as a second- or third-line therapy after treatment failure with sorafenib or sunitinib. The median duration of everolimus therapy was 6.7 months, whereas that of temsirolimus was 9.5 months. All patients had stable disease as the best response during each period of therapy. There were no severe adverse events. The use of mammalian target of rapamycin inhibitors in patients who previously failed to respond to tyrosine kinase inhibitors appears to be feasible in patients with end-stage renal disease requiring hemodialysis. PMID- 26833675 TI - Biomimetic Assembly Lines Producing Natural Product Analogs: Strategies from a Versatile Manifold to Skeletally Diverse Scaffolds. AB - Biosynthetic assembly lines have evolved in nature, adopting divergent processes to produce a vast number of secondary metabolites. Inspired by these biogenetic processes, this account introduces recent investigations by my research group to formulate a synthetic strategy for establishing a biomimetic assembly line. With the aim not only to construct natural product-relevant scaffolds within 5-7 steps, but also to systematically diversify skeletal and stereochemical properties and functional groups, divergent synthetic processes exploiting a versatile manifold have been developed. This approach allows for cost-effective production of skeletally diverse and biologically active natural product analogs inaccessible by other means. Discovery of several lead candidates for a neglected tropical disease is a proof-of-concept of this synthetic approach. PMID- 26833676 TI - The relationship of social support with treatment adherence and weight loss in Latinos with type 2 diabetes. AB - OBJECTIVE: Little is known about the effects of social support on weight loss in Latinos. This study determined whether sex moderated and treatment adherence mediated the association between social support and weight loss. METHODS: Data from 278 Latino males and females with type 2 diabetes in the Intensive Lifestyle Intervention of the Look AHEAD trial were analyzed. Multivariable modeling tested for moderation and parallel multiple mediator modeling simultaneously tested the mediating effects of adherence to physical activity, diet, and session attendance on the relationship between baseline social support and percent weight loss at 1 year. RESULTS: Social support for physical activity (having family and friends join in physical activity) was related to weight loss. Adherence to physical activity was related to both social support for physical activity and weight loss. Sex did not moderate these relationships. Adherence to physical activity completely mediated the relationship between social support for physical activity and weight loss. CONCLUSIONS: Increasing companionship for physical activity may be an effective intervention strategy to promote behaviors important for weight loss among Latinos. PMID- 26833677 TI - Drug Repurposing Identifies Inhibitors of Oseltamivir-Resistant Influenza Viruses. AB - The neuraminidase (NA) inhibitor, oseltamivir, is a widely used anti-influenza drug. However, oseltamivir-resistant H1N1 influenza viruses carrying the H275Y NA mutation spontaneously emerged as a result of natural genetic drift and drug treatment. Because H275Y and other potential mutations may generate a future pandemic influenza strain that is oseltamivir-resistant, alternative therapy options are needed. Herein, we show that a structure-based computational method can be used to identify existing drugs that inhibit resistant viruses, thereby providing a first line of pharmaceutical defense against this possible scenario. We identified two drugs, nalidixic acid and dorzolamide, that potently inhibit the NA activity of oseltamivir-resistant H1N1 viruses with the H275Y NA mutation at very low concentrations, but have no effect on wild-type H1N1 NA even at a much higher concentration, suggesting that the oseltamivir-resistance mutation itself caused susceptibility to these drugs. PMID- 26833678 TI - The toxin GraT inhibits ribosome biogenesis. AB - Most bacteria encode numerous chromosomal toxin-antitoxin (TA) systems that are proposed to contribute to stress tolerance, as they are able to shift the cells to a dormant state. Toxins act on a variety of targets with the majority attacking the translational apparatus. Intriguingly, the toxicity mechanisms of even closely related toxins may differ essentially. Here, we report on a new type of TA toxin that inhibits ribosome biogenesis. GraT of the GraTA system has previously been described in Pseudomonas putida as an unusually moderate toxin at optimal growth temperatures. However, GraT causes a severe growth defect at lower temperatures. Here, we demonstrate that GraT causes the accumulation of free ribosomal subunits. Mapping the rRNA 5' ends reveals incomplete processing of the free subunits and quantification of modified nucleosides shows an underrepresentation of late subunit assembly specific modifications. This indicates that GraT inhibits ribosome subunit assembly. Interestingly, GraT effects can be alleviated by modification of the chaperone DnaK, a known facilitator of late stages in ribosome biogenesis. We show that GraT directly interacts with DnaK and suggest two possible models for the role of this interaction in GraT toxicity. PMID- 26833679 TI - Single substitutions to closely related amino acids contribute to the functional diversification of an insect-inducible, positively selected plant cystatin. AB - A causal link has been reported between positively selected amino acids in plant cystatins and the inhibitory range of these proteins against insect digestive cysteine (Cys) proteases. Here we assessed the impact of single substitutions to closely related amino acids on the contribution of positive selection to cystatin diversification. Cystatin sequence alignments, while confirming hypervariability, indicated a preference for related amino acids at positively selected sites. For example, the non-polar residues leucine (Leu), isoleucine (Ile) and valine (Val) were shown to predominate at positively selected site 2 in the N-terminal region, unlike selected sites 6 and 10, where polar residues are preferred. The model cystatin SlCYS8 and single variants with Leu, Ile or Val at position 2 were compared with regard to their ability to bind digestive proteases of the coleopteran pest Leptinotarsa decemlineata and to induce compensatory responses in this insect. A functional proteomics procedure to capture target Cys proteases in midgut extracts allowed confirmation of distinct binding profiles for the cystatin variants. A shotgun proteomics procedure to monitor whole Cys protease complements revealed protease family specific compensatory responses in the insect, dependent on the variant ingested. Our data confirm the contribution of closely related amino acids to the functional diversity of positively selected plant cystatins in a broader structure/function context imposing physicochemical constraints to primary structure alterations. They also underline the complexity of protease/inhibitor interactions in plant-insect systems, and the challenges still to be met in order to harness the full potential of ectopically expressed protease inhibitors in crop protection. PMID- 26833680 TI - Utilization of Deceased Donor Kidneys to Initiate Living Donor Chains. AB - We propose that some deceased donor (DD) kidneys be allocated to initiate nonsimultaneous extended altruistic donor chains of living donor (LD) kidney transplants to address, in part, the huge disparity between patients on the DD kidney waitlist and available donors. The use of DD kidneys for this purpose would benefit waitlisted candidates in that most patients enrolled in kidney paired donation (KPD) systems are also waitlisted for a DD kidney transplant, and receiving a kidney through the mechanism of KPD will decrease pressure on the DD pool. In addition, a LD kidney usually provides survival potential equal or superior to that of DD kidneys. If KPD chains that are initiated by a DD can end in a donation of an LD kidney to a candidate on the DD waitlist, the quality of the kidney allocated to a waitlisted patient is likely to be improved. We hypothesize that a pilot program would show a positive impact on patients of all ethnicities and blood types. PMID- 26833681 TI - Adding insult to injury: heart failure and incident cancer. PMID- 26833683 TI - Structures and energetics of complexation of metal ions with ammonia, water, and benzene: A computational study. AB - Quantum chemical calculations have been performed at CCSD(T)/def2-TZVP level to investigate the strength and nature of interactions of ammonia (NH3 ), water (H2 O), and benzene (C6 H6 ) with various metal ions and validated with the available experimental results. For all the considered metal ions, a preference for C6 H6 is observed for dicationic ions whereas the monocationic ions prefer to bind with NH3 . Density Functional Theory-Symmetry Adapted Perturbation Theory (DFT-SAPT) analysis has been employed at PBE0AC/def2-TZVP level on these complexes (closed shell), to understand the various energy terms contributing to binding energy (BE). The DFT-SAPT result shows that for the metal ion complexes with H2 O electrostatic component is the major contributor to the BE whereas, for C6 H6 complexes polarization component is dominant, except in the case of alkali metal ion complexes. However, in case of NH3 complexes, electrostatic component is dominant for s-block metal ions, whereas, for the d and p-block metal ion complexes both electrostatic and polarization components are important. The geometry (M(+) -N and M(+) -O distance for NH3 and H2 O complexes respectively, and cation-pi distance for C6 H6 complexes) for the alkali and alkaline earth metal ion complexes increases down the group. Natural population analysis performed on NH3 , H2 O, and C6 H6 complexes shows that the charge transfer to metal ions is higher in case of C6 H6 complexes. PMID- 26833682 TI - The conserved apicomplexan Aurora kinase TgArk3 is involved in endodyogeny, duplication rate and parasite virulence. AB - Aurora kinases are eukaryotic serine/threonine protein kinases that regulate key events associated with chromatin condensation, centrosome and spindle function and cytokinesis. Elucidating the roles of Aurora kinases in apicomplexan parasites is crucial to understand the cell cycle control during Plasmodium schizogony or Toxoplasma endodyogeny. Here, we report on the localization of two previously uncharacterized Toxoplasma Aurora-related kinases (Ark2 and Ark3) in tachyzoites and of the uncharacterized Ark3 orthologue in Plasmodium falciparum erythrocytic stages. In Toxoplasma gondii, we show that TgArk2 and TgArk3 concentrate at specific sub-cellular structures linked to parasite division: the mitotic spindle and intranuclear mitotic structures (TgArk2), and the outer core of the centrosome and the budding daughter cells cytoskeleton (TgArk3). By tagging the endogenous PfArk3 gene with the green fluorescent protein in live parasites, we show that PfArk3 protein expression peaks late in schizogony and localizes at the periphery of budding schizonts. Disruption of the TgArk2 gene reveals no essential function for tachyzoite propagation in vitro, which is surprising giving that the P. falciparum and P. berghei orthologues are essential for erythrocyte schizogony. In contrast, knock-down of TgArk3 protein results in pronounced defects in parasite division and a major growth deficiency. TgArk3 depleted parasites display several defects, such as reduced parasite growth rate, delayed egress and parasite duplication, defect in rosette formation, reduced parasite size and invasion efficiency and lack of virulence in mice. Our study provides new insights into cell cycle control in Toxoplasma and malaria parasites and highlights Aurora kinase 3 as potential drug target. PMID- 26833685 TI - Erratum. PMID- 26833684 TI - The genomic landscape of cutaneous melanoma. AB - Somatic mutation analysis of melanoma has been performed at the single gene level extensively over the past several decades. This has provided considerable insight into the critical pathways controlling melanoma initiation and progression. During the last 5 yr, next-generation sequencing (NGS) has enabled even more comprehensive mutational screening at the level of multigene panels, exomes and genomes. These studies have uncovered many new and unexpected players in melanoma development. The recent landmark study from The Cancer Genome Atlas (TCGA) consortium describing the genomic architecture of 333 cutaneous melanomas provides the largest and broadest analysis to date on the somatic aberrations underlying melanoma genesis. It thus seems timely to review the mutational landscape of melanoma and highlight the key genes and cellular pathways that appear to drive this cancer. PMID- 26833686 TI - Detailed evaluation of different (68)Ge/(68)Ga generators: an attempt toward achieving efficient (68)Ga radiopharmacy. AB - The present study is aimed at carrying out a comparative performance evaluation of different types of (68)Ge/(68)Ga generators to identify the best choice for use in (68)Ga-radiopharmacy. Over the 1 year period of evaluation, the elution yields from the CeO2-based and SiO2-based (68)Ge/(68) Ga generators remained almost consistent, in contrast to the sharp decrease observed in the elution yields from TiO2 and SnO2-based generators. The level of (68)Ge impurity in (68)Ga eluates from the CeO2 and SiO2-based (68)Ge/(68)Ga generator was always <10(-3)%, while this level increased from 10(-3)% to 10(-1)% in case of TiO2 and SnO2-based generators. The level of chemical impurities in (68)Ga eluates from CeO2 and SiO2-based (68)Ge/(68)Ga generators was negligibly low (<0.1 ppm) in contrast to the significantly higher level (1-20 ppm) of such impurities in eluates from other two generators. As demonstrated by radiolabeling studies carried out using DOTA-coupled dimeric cyclic RGD peptide derivative (DOTA-RGD2), CeO2-PAN and SiO2-based generators are directly amenable for radiopharmaceutical preparation, whereas the other generators can be only used after post-elution purification of (68)Ga eluates. Clinically relevant dose of (68)Ga-DOTA-RGD2 was prepared in a hospital radiopharmacy for non-invasive visualization of tumors in breast cancer patients using positron emission tomography. PMID- 26833687 TI - Moral Enhancement and Those Left Behind. AB - Opponents to genetic or biomedical human enhancement often claim that the availability of these technologies would have negative consequences for those who either choose not to utilize these resources or lack access to them. However, Thomas Douglas has argued that this objection has no force against the use of technologies that aim to bring about morally desirable character traits, as the unenhanced would benefit from being surrounded by such people. I will argue that things are not as straightforward as Douglas makes out. The widespread use of moral enhancement would raise the standards for praise and blame worthiness, making it much harder for the unenhanced to perform praiseworthy actions or avoid performing blameworthy actions. This shows that supporters of moral enhancement cannot avoid this challenge in the way that Douglas suggests. PMID- 26833688 TI - Proline accumulation protects Saccharomyces cerevisiae cells in stationary phase from ethanol stress by reducing reactive oxygen species levels. AB - During fermentation processes, Saccharomyces cerevisiae cells are exposed to multiple stresses, including a high concentration of ethanol that represents toxicity through intracellular reactive oxygen species (ROS) generation. We previously reported that proline protected yeast cells from damage caused by various stresses, such as freezing and ethanol. As an anti-oxidant, proline is suggested to scavenge intracellular ROS. In this study, we examined the role of intracellular proline during ethanol treatment in S. cerevisiae strains that accumulate different concentrations of proline. When cultured in YPD medium, there was a significant accumulation of proline in the put1 mutant strain, which is deficient in proline oxidase, in the stationary phase. Expression of the mutant PRO1 gene, which encodes the gamma-glutamyl kinase variant (Asp154Asn or Ile150Thr) with desensitization to feedback inhibition by proline in the put1 mutant strain, showed a prominent increase in proline content as compared with that of the wild-type strain. The oxidation level was clearly increased in wild type cells after exposure to ethanol, indicating that the generation of ROS occurred. Interestingly, proline accumulation significantly reduces the ROS level and increases the survival rate of yeast cells in the stationary phase under ethanol stress conditions. However, there was not a clear correlation between proline content and survival rate in yeast cells. An appropriate level of intracellular proline in yeast might be important for its stress-protective effect. Hence, the engineering of proline metabolism could be promising for breeding stress-tolerant industrial yeast strains. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833689 TI - Extraordinarily Strong Interlayer Interaction in 2D Layered PtS2. AB - Platinum disulfide (PtS2 ), a new member of the group-10 transition-metal dichalcogenides, is studied experimentally and theoretically. The indirect bandgap of PtS2 can be drastically tuned from 1.6 eV (monolayer) to 0.25 eV (bulk counterpart), and the interlayer mechanical coupling is almost isotropic. It can be explained by strongly interlayer interaction from the pz orbital hybridization of S atoms. PMID- 26833690 TI - Classification of proteins with shared motifs and internal repeats in the ECOD database. AB - Proteins and their domains evolve by a set of events commonly including the duplication and divergence of small motifs. The presence of short repetitive regions in domains has generally constituted a difficult case for structural domain classifications and their hierarchies. We developed the Evolutionary Classification Of protein Domains (ECOD) in part to implement a new schema for the classification of these types of proteins. Here we document the ways in which ECOD classifies proteins with small internal repeats, widespread functional motifs, and assemblies of small domain-like fragments in its evolutionary schema. We illustrate the ways in which the structural genomics project impacted the classification and characterization of new structural domains and sequence families over the decade. PMID- 26833691 TI - Ultrasound-guided core needle biopsies for workup of lymphadenopathy and lymphoma. AB - BACKGROUND: For the histopathological diagnosis of lymphoma, lymph node excision biopsies are regarded as standard of care. In contrast, for the diagnosis of carcinoma and deep-seated tumors, core needle biopsies (CNBs) are accepted as a sufficient sampling method. We evaluated a diagnostic algorithm for peripheral lymphadenopathy starting with ultrasound-guided CNB followed by excisional biopsy in ambiguous cases. METHODS: We performed ultrasound-guided CNB of peripheral lymph nodes and subcutaneous tumors in patients with lymphadenopathy in routine care and analyzed its accuracy, complication rate, and the impact of needle sizes on results. RESULTS: From 138 patients, 132 samples were technically adequate. In 121 patients, CNB provided a clinically actionable diagnosis (76 lymphoma, 30 carcinoma, 15 non-malignant diagnoses). A total of 54 patients had a secondary biopsy. Inconclusive diagnoses were rare with two false-positive and two false negative non-Hodgkin's lymphoma, and higher for Hodgkin's lymphoma with five false-negative cases. The rate of complications was low. Needle size did not significantly influence results. CONCLUSION: Ultrasound-guided CNBs are a safe, quick, and valid tool for the workup of lymphadenopathy. Yet, a benign diagnosis from CNB must be completed by a secondary biopsy if clinical presentation suggests malignant disease. PMID- 26833692 TI - Stable Crystalline Forms of Na Polysulfides: Experiment versus Ab Initio Computational Prediction. AB - For the design of light-metal-sulfur batteries and for the understanding of their performance, knowledge on the stable crystalline polysulfides is very important. We confronted experimental and ab initio crystal structure prediction studies on the stability of Na polysulfides. The selected evolutionary-based structure prediction algorithm was able to quickly and correctly predict the thermodynamically stable crystalline forms of Na polysulfides with small unit cells. For Na polysulfides with large unit cells, the algorithm correctly proposed short unbranched polysulfide chains to be energetically favorite structural motifs, but could not find proper three-dimensional structures in the limited number of generations. Experimentally, the polysulfides were studied by X ray diffraction and 23 Na solid-state NMR spectroscopy. Complemented by calculations of the isotropic chemical shifts and quadrupolar coupling constants, NMR spectroscopy proved to be an excellent tool for the examination of Na polysulfides, because it allowed easy distinction and quantification of components in the samples. PMID- 26833693 TI - Cancer diagnosed in the Emergency Department of a Regional Health Service. AB - OBJECTIVE: Patients diagnosed with cancer in the Emergency Department (ED) have more advanced disease at diagnosis and poorer outcomes. High rates of initial presentation to ED suggest potential problems with access to care. The aim of this project was to interpret findings in regional/rural Victoria and explore implications for practice. DESIGN: Cross-sectional study linking two independent data sets. SETTING: Regional city of Geelong and surrounding rural areas in south west Victoria. PARTICIPANTS: All newly diagnosed cancer patients in 2009. MAIN OUTCOME MEASURES: Number of cancer patients diagnosed in the ED. RESULTS: One in five newly diagnosed cancer patients present to ED 6 months prior to cancer diagnosis. One in 10 is diagnosed as a result of their ED visit. Patients presenting to ED were older, more often men and from disadvantaged areas. Symptoms on presentation included chest complaints, bowel obstruction, abdominal pain, anaemia and generalised weakness. Cancer diagnosed in the ED is associated with advanced stage and shorter survival. CONCLUSION: Reasons for presentation to ED would be multifactorial and include complex cases with coexisting symptoms making diagnosis difficult. The general public appear to have a low level of awareness of alternative primary care services or difficulty accessing such information. Some of the changes towards reducing the number of patients presenting to ED will include patient education. PMID- 26833694 TI - Phenological change in a spring ephemeral: implications for pollination and plant reproduction. AB - Climate change has had numerous ecological effects, including species range shifts and altered phenology. Altering flowering phenology often affects plant reproduction, but the mechanisms behind these changes are not well-understood. To investigate why altering flowering phenology affects plant reproduction, we manipulated flowering phenology of the spring herb Claytonia lanceolata (Portulacaceae) using two methods: in 2011-2013 by altering snow pack (snow removal vs. control treatments), and in 2013 by inducing flowering in a greenhouse before placing plants in experimental outdoor arrays (early, control, and late treatments). We measured flowering phenology, pollinator visitation, plant reproduction (fruit and seed set), and pollen limitation. Flowering occurred approx. 10 days earlier in snow-removal than control plots during all years of snow manipulation. Pollinator visitation patterns and strength of pollen limitation varied with snow treatments, and among years. Plants in the snow removal treatment were more likely to experience frost damage, and frost-damaged plants suffered low reproduction despite lack of pollen limitation. Plants in the snow removal treatment that escaped frost damage had higher pollinator visitation rates and reproduction than controls. The results of the array experiment supported the results of the snow manipulations. Plants in the early and late treatments suffered very low reproduction due either to severe frost damage (early treatment) or low pollinator visitation (late treatment) relative to control plants. Thus, plants face tradeoffs with advanced flowering time. While early-flowering plants can reap the benefits of enhanced pollination services, they do so at the cost of increased susceptibility to frost damage that can overwhelm any benefit of flowering early. In contrast, delayed flowering results in dramatic reductions in plant reproduction through reduced pollination. Our results suggest that climate change may constrain the success of early-flowering plants not through plant-pollinator mismatch but through the direct impacts of extreme environmental conditions. PMID- 26833695 TI - Renal artery embolization in severe nephrotic syndrome. AB - Introduction Severe nephrotic syndrome is associated with increased morbidity and mortality. Renal artery embolization (RAE) has been used in a number of renal diseases such as renal tumors, arteriovenous fistulas etc. However, data regarding benefits of RAE in patients with symptomatic severe proteinuria is limited. We decided to evaluate role of RAE in the setting of severe symptomatic nephrotic syndrome. Methods Eight patients who had undergone transcatheter renal artery embolization with polyvinyl alcohol (PVA) were included. Clinico demographic characteristics as well as baseline laboratory data including level of proteinuria, serum albumin, C-reactive protein and LDL cholesterol levels were recorded for each patient. After RAE, outpatient clinic control laboratory values were also assessed. Findings All patients except one underwent bilateral RAE (four simultaneous or three sequential). Two patients experienced postembolization syndrome characterized by flank pain, fever, and leukocytosis, which was self-limited and responded to analgesics in all patients. There was no technical complications associated with RAE procedure. All patients became anuric except one. Serum albumin levels increased and serum LDL-cholesterol levels decreased considerably in treated patients. Discussion Renal artery embolization with the purpose of amelioration in nephrotic syndrome complications was effective and free of major technical complications in our patients. PMID- 26833696 TI - Retrieval analysis of a failed TriboFit polycarbonate urethane acetabular buffer. AB - The purpose of this research was to determine the failure mechanisms and damage features of a TriboFit acetabular buffer implanted directly against a native, prepared acetabulum which was revised after 11months. Retrieval analyses were carried out via light microscopy, gravimetric wear assessment, and observer scoring of visible damage features on the buffer. The volume of material abraded from the backside of the buffer was estimated via three-dimensional reconstruction using a laser scanner. Scanning electron microscopy was used to confirm damage features and mechanisms. Severe abrasion to the backside of the buffer was the primary damage feature, while stippling damage was seen on the articular surface of the buffer. Material loss due to backside abrasion was approximated to be between 0.13360.085 g (gravimetric analyses) and 0.19360.053 g (three-dimensional reconstruction). Implantation of the TriboFit buffer against the patient's native acetabulum without a metal backing allowed for significant movement of the buffer against the bone, resulting in the abrasion seen on this implant. The stippling damage on the articular surface indicates an adhesive wear mechanism which exacerbates movement of the buffer against the acetabulum, thereby increasing backside abrasion. PMID- 26833697 TI - The design and development of a finger joint simulator. AB - Artificial finger joints lack the long-term clinical success seen with hip and knee prostheses. In part, this can be explained by the challenges of rheumatoid arthritis, a progressive disease which attacks surrounding tissues as well as the joint itself. Therefore, the natural finger joints' biomechanics are adversely affected, and consequently, this imbalance due to subluxing forces further challenges any prosthesis. Many different designs of finger prosthesis have been offered over a period of greater than 50 years. Most of these designs have failed, and it is likely that many of these failures could have been identified had the prostheses been appropriately tested prior to implantation into patients. While finger joint simulators have been designed, arguably only those from a single centre have been able to reproduce clinical-type failures of the finger prostheses tested in them. This article describes the design and development of a finger simulator at Durham University, UK. It explains and justifies the engineering decisions made and thus the evolution of the finger simulator. In vitro results and their linkage to clinical-type failures are outlined to help to show the effectiveness of the simulator. Failures of finger implants in vivo continue to occur, and the need for appropriate in vitro testing of finger prostheses remains strong. PMID- 26833698 TI - Telepressure and College Student Employment: The Costs of Staying Connected Across Social Contexts. AB - Telepressure is a psychological state consisting of the preoccupation and urge to respond quickly to message-based communications from others. Telepressure has been linked with negative stress and health outcomes, but the existing measure focuses on experiences specific to the workplace. The current study explores whether an adapted version of the workplace telepressure measure is relevant to general social interactions that rely on information and communication technologies. We validated a general telepressure measure in a sample of college students and found psychometric properties similar to the original workplace measure. Also, general telepressure was related to, but distinct from, the fear of missing out, self-control and technology use. Using a predictive validity design, we also found that telepressure at the beginning of the semester was related to student reports of burnout, perceived stress and poor sleep hygiene 1 month later (but not work-life balance or general life satisfaction). Moreover, telepressure was more strongly related to more negative outcomes (burnout, stress and poor sleep hygiene) and less positive outcomes (work-life balance and life satisfaction) among employed compared with non-employed students. Thus, the costs of staying connected to one's social network may be more detrimental to college students with additional employment obligations. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833700 TI - Cellular Synthesis of Protein Catenanes. AB - Direct cellular production of topologically complex proteins is of great interest both in supramolecular chemistry and protein engineering. We describe the first cellular synthesis of protein catenanes through the use of the p53 dimerization domain to guide the intertwining of two protein chains and SpyTag-SpyCatcher chemistry for efficient cyclization. The catenane topology was unambiguously proven by SDS-PAGE, SEC, and partial digestion experiments and was shown to confer enhanced stability toward trypsin digestion relative to monomeric control mutants. The assembly-reaction synergy enabled by protein folding and genetically encoded protein chemistry offers a convenient yet powerful approach for creating mechanically interlocked, complex protein topologies in vivo. PMID- 26833699 TI - Interpregnancy weight change and risk of preterm delivery. AB - OBJECTIVE: Prepregnant weight gain increases risk of obstetric complications, but its effect on preterm delivery is unknown. This study aimed to investigate the associations between change in body mass index (BMI) from first to second pregnancies and risk of preterm delivery in the second pregnancy according to the type and severity of preterm delivery. METHODS: A nationwide cohort study was conducted in 465,836 Swedish women with their first two consecutive singleton live births between 1992 and 2012. Rates of very (22-31 gestational weeks) and moderately (32-36 gestational weeks) preterm delivery in the second pregnancy, classified as spontaneous or medically indicated, were compared between categories of interpregnancy BMI change. RESULTS: Among women with first pregnancy BMI < 25, BMI gain >= 4 kg/m(2) and BMI loss > 2 kg/m(2) were related to 24% (95% CI, 5-46%) and 18% (95% CI, 5-33%) higher rates of spontaneous moderately preterm delivery, respectively. BMI gain >= 4 kg/m(2) was related to increased risk of medically indicated very preterm delivery. Weight loss was associated with reduced rates of medically indicated moderately preterm delivery among women with BMI >= 25. CONCLUSIONS: High weight gain or loss in normal weight women is associated with spontaneous moderately preterm delivery. High interpregnancy weight gain is related to increased risks of medically indicated preterm delivery. PMID- 26833701 TI - Surgical induction of posterior vitreous detachment using combined sharp dissection and active aspiration. PMID- 26833702 TI - Enabling cell-cell communication via nanopore formation: structure, function and localization of the unique cell wall amidase AmiC2 of Nostoc punctiforme. AB - To orchestrate a complex life style in changing environments, the filamentous cyanobacterium Nostoc punctiforme facilitates communication between neighboring cells through septal junction complexes. This is achieved by nanopores that perforate the peptidoglycan (PGN) layer and traverse the cell septa. The N acetylmuramoyl-l-alanine amidase AmiC2 (Npun_F1846; EC 3.5.1.28) in N. punctiforme generates arrays of such nanopores in the septal PGN, in contrast to homologous amidases that mediate daughter cell separation after cell division in unicellular bacteria. Nanopore formation is therefore a novel property of AmiC homologs. Immunofluorescence shows that native AmiC2 localizes to the maturing septum. The high-resolution crystal structure (1.12 A) of its catalytic domain (AmiC2-cat) differs significantly from known structures of cell splitting and PGN recycling amidases. A wide and shallow binding cavity allows easy access of the substrate to the active site, which harbors an essential zinc ion. AmiC2-cat exhibits strong hydrolytic activity in vitro. A single point mutation of a conserved glutamate near the zinc ion results in total loss of activity, whereas zinc removal leads to instability of AmiC2-cat. An inhibitory alpha-helix, as found in the Escherichia coli AmiC(E. coli) structure, is absent. Taken together, our data provide insight into the cell-biological, biochemical and structural properties of an unusual cell wall lytic enzyme that generates nanopores for cell cell communication in multicellular cyanobacteria. The novel structural features of the catalytic domain and the unique biological function of AmiC2 hint at mechanisms of action and regulation that are distinct from other amidases. DATABASE: The AmiC2-cat structure has been deposited in the Protein Data Bank under accession number 5EMI. PMID- 26833703 TI - Favorable outcome to glucocorticoid therapy for engraftment syndrome in pediatric autologous hematopoietic cell transplant. AB - ES remains an important cause of morbidity and mortality in children undergoing auto-HCT. Glucocorticoid use in ES is an area of debate. We retrospectively analyzed single-institution experience from September 2000 through December 2012 to evaluate the use of glucocorticoids in auto-HCT patients. ES was defined by the occurrence of new onset of non-infectious fever plus diarrhea, rash, or pulmonary infiltrates 24-h before or within five days after neutrophil engraftment. Sixty-five pediatric patients (<21 yr) with different solid tumors underwent auto-HCTs in the study period. Fifteen patients (23%) fulfilled criteria for ES, of which 13 received methylprednisolone (2 mg/kg IV for 3-5 days). Clinical improvement occurred in all patients within 48 h without significant complications. In the non-ES group, 11 patients received glucocorticoid without significant complications as well. MEL-based regimens were found to be significant factor for ES (p < 0.05). Fever, edema, non-infectious diarrhea, and serum albumin concentration were statistically different between the two groups. Median hospital length of stay was higher in the ES group. CONCLUSION: ES is a common complication in children after auto-HCT and short course glucocorticoid therapy is an effective and well-tolerated treatment, even in those who did not completely fulfill diagnostic criteria. PMID- 26833704 TI - A low-cost, user-friendly electroencephalographic recording system for the assessment of hepatic encephalopathy. AB - Electroencephalography (EEG) is useful to objectively diagnose/grade hepatic encephalopathy (HE) across its spectrum of severity. However, it requires expensive equipment, and hepatogastroenterologists are generally unfamiliar with its acquisition/interpretation. Recent technological advances have led to the development of low-cost, user-friendly EEG systems, allowing EEG acquisition also in settings with limited neurophysiological experience. The aim of this study was to assess the relationship between EEG parameters obtained from a standard-EEG system and from a commercial, low-cost wireless headset (light-EEG) in patients with cirrhosis and varying degrees of HE. Seventy-two patients (58 males, 61 +/- 9 years) underwent clinical evaluation, the Psychometric Hepatic Encephalopathy Score (PHES), and EEG recording with both systems. Automated EEG parameters were calculated on two derivations. Strong correlations were observed between automated parameters obtained from the two EEG systems. Bland and Altman analysis indicated that the two systems provided comparable automated parameters, and agreement between classifications (normal versus abnormal EEG) based on standard EEG and light-EEG was good (0.6 < kappa < 0.8). Automated parameters such as the mean dominant frequency obtained from the light-EEG correlated significantly with the Model for End-Stage Liver Disease score (r = -0.39, P < 0.05), fasting venous ammonia levels (r = -0.41, P < 0.01), and PHES (r = -0.49, P < 0.001). Finally, significant differences in light-EEG parameters were observed in patients with varying degrees of HE. CONCLUSION: Reliable EEG parameters for HE diagnosing/grading can be obtained from a cheap, commercial, wireless headset; this may lead to more widespread use of this patient-independent tool both in routine liver practice and in the research setting. ( PMID- 26833705 TI - Heterogeneity identified at birth and blood pressure in adulthood. AB - OBJECTIVE: In the developmental programming literature, the association of birth weight and blood pressure later in life is modest at best. This article reexamines this issue using Covariate Density Defined mixture of regressions (CDDmr) to determine if a latent variable, based on birth weight, and known to influence infant mortality, provides a stronger indicator of developmental programming. METHODS: CDDmr identifies two latent components in the birth weight distribution, generally interpreted in the infant mortality literature as "compromised" and "normal" fetal development. The data are taken from the 1958 British National Child Development Study. RESULTS: In the 1958 cohort, the "compromised" component consists of about 10% of the birth weight distribution. Compared to "normal" births, the mean systolic blood pressure at age 45 of "compromised" births is 20.3 (females) and 26.4 (males) mm Hg higher than "normal" births. The relative risks of stage-I-II systolic hypertension (>140 mm Hg) of "compromised" births compared to "normal" births are 10.7 (females) and 4.2 (males). The relative risks of stage-II systolic hypertension (>160 mm Hg) are considerably higher, 241.6 (females) and 74.3 (males). In general, the highest blood pressures are observed in "compromised" births with birth weights within the normal (about 3.0-3.5 kg) birth weight range. Results for diastolic blood pressure are similar. CONCLUSIONS: These associations are much stronger than those identified using conventional methods. CDDmr is likely to be useful for studying the dynamics of developmental programming particularly in large cohort studies where birth weight is often the only indicator of programming available. Am. J. Hum. Biol. 28:545-554, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26833707 TI - miR-708/LSD1 axis regulates the proliferation and invasion of breast cancer cells. AB - Breast cancer is one of the most common malignant tumors in women worldwide. The microRNAs (miRNAs) are small, noncoding RNAs that regulate various biological processes, including breast cancer. miR-708 played an important role in a variety of cancers. However, its involvement in breast cancer remains largely unclear. In this study, we found that forced the expression of miR-708 in breast cancer cell lines decreased cell proliferation and invasion, whereas inhibition of miR-708 increased cell growth and invasion. miR-708 could directly target the LSD1 3'UTR to downregulate the expression. Further studies suggested that inhibition of LSD1 could phenocopied function of the miR-708 overexpression in MDA-MB-231 cells .Overexpression of LSD1 could counteract the effects of miR-708 on the proliferation and invasion. Taken together, the results indicate that miR-708 may function as a tumor suppressor gene in breast cancer development, and miR 708/LSD1 axis may be a therapeutic intervention in breast cancer in the future. PMID- 26833706 TI - Fast search algorithms for computational protein design. AB - One of the main challenges in computational protein design (CPD) is the huge size of the protein sequence and conformational space that has to be computationally explored. Recently, we showed that state-of-the-art combinatorial optimization technologies based on Cost Function Network (CFN) processing allow speeding up provable rigid backbone protein design methods by several orders of magnitudes. Building up on this, we improved and injected CFN technology into the well established CPD package Osprey to allow all Osprey CPD algorithms to benefit from associated speedups. Because Osprey fundamentally relies on the ability of A* to produce conformations in increasing order of energy, we defined new A* strategies combining CFN lower bounds, with new side-chain positioning-based branching scheme. Beyond the speedups obtained in the new A*-CFN combination, this novel branching scheme enables a much faster enumeration of suboptimal sequences, far beyond what is reachable without it. Together with the immediate and important speedups provided by CFN technology, these developments directly benefit to all the algorithms that previously relied on the DEE/ A* combination inside Osprey* and make it possible to solve larger CPD problems with provable algorithms. PMID- 26833708 TI - Dihydro-Resveratrol Ameliorates Lung Injury in Rats with Cerulein-Induced Acute Pancreatitis. AB - Acute pancreatitis is an inflammatory process originated in the pancreas; however, it often leads to systemic complications that affect distant organs. Acute respiratory distress syndrome is indeed the predominant cause of death in patients with severe acute pancreatitis. In this study, we aimed to delineate the ameliorative effect of dihydro-resveratrol, a prominent analog of trans resveratrol, against acute pancreatitis-associated lung injury and the underlying molecular actions. Acute pancreatitis was induced in rats with repetitive injections of cerulein (50 ug/kg/h) and a shot of lipopolysaccharide (7.5 mg/kg). By means of histological examination and biochemical assays, the severity of lung injury was assessed in the aspects of tissue damages, myeloperoxidase activity, and levels of pro-inflammatory cytokines. When treated with dihydro-resveratrol, pulmonary architectural distortion, hemorrhage, interstitial edema, and alveolar thickening were significantly reduced in rats with acute pancreatitis. In addition, the production of pro-inflammatory cytokines and the activity of myeloperoxidase in pulmonary tissues were notably repressed. Importantly, nuclear factor-kappaB (NF-kappaB) activation was attenuated. This study is the first to report the oral administration of dihydro-resveratrol ameliorated acute pancreatitis-associated lung injury via an inhibitory modulation of pro inflammatory response, which was associated with a suppression of the NF-kappaB signaling pathway. PMID- 26833709 TI - Nickel(II) meso-Hydroxyporphyrin Complexes Revisited: Palladium-Catalysed Synthesis, Electronic Structures of Derived Oxy Radicals, and Oxidative Coupling to a Dioxoporphodimethene Dyad. AB - We report the synthesis and characterisation of new examples of meso hydroxynickel(II) porphyrins with 5,15-diphenyl and 10-phenyl-5,15 diphenyl/diaryl substitution. The OH group was introduced by using carbonate or hydroxide as nucleophile by using palladium/phosphine catalysis. The NiPor-OHs exist in solution in equilibrium with the corresponding oxy radicals NiPor-O. . The 15-phenyl group stabilises the radicals, so that the 1 H NMR spectra of {NiPor-OH} are extremely broad due to chemical exchange with the paramagnetic species. The radical concentration for the diphenylporphyrin analogue is only 1 %, and its NMR line-broadening was able to be studied by variable-temperature NMR spectroscopy. The EPR signals of NiPor-O. are consistent with somewhat delocalised porphyrinyloxy radicals, and the spin distributions calculated by using density functional theory match the EPR and NMR spectroscopic observations. Nickel(II) meso-hydroxy-10,20-diphenylporphyrin was oxidatively coupled to a dioxo-terminated porphodimethene dyad, the strongly red-shifted electronic spectrum of which was successfully modelled by using time-dependent DFT calculations. PMID- 26833710 TI - Human Milk Analyser shows that the lactation period affects protein levels in preterm breastmilk. AB - AIM: This study measured the composition of preterm human breastmilk, particularly the protein content, with the MIRIS Human Milk Analyser, compared our results with published values and determined the relationship between protein content and lactation period. METHODS: We analysed 83 samples of 24-hour pooled human milk from 76 mothers who delivered preterm infants weighing under 1500 g at less than 32 weeks of gestational age. The milk's protein, fat and energy were measured by the MIRIS Human Milk Analyser and compared to reference values. The relationship between protein content and lactation period was quantified. RESULTS: On average, the samples contained 1.1 +/- 0.37 g (0.2-2.2 g) of protein, 3.2 +/- 0.85 g (range 1.1-6.1 g) of fat, 6.6 +/- 0.34 g of lactose (5.5-8.0 g) and 60 +/- 11 kcal (39-94 kcal) of energy per 100 mL. The wide variations in macronutrient content were not influenced by the gestational age of the infant and the lactation day results from 70 of the mothers correlated inversely with the protein content (p < 0.0001; r = -0.42). The MIRIS proved useful, but some adjustments are needed. CONCLUSION: Variations in macronutrients were high in the breastmilk of women who delivered preterm babies and the protein content decreased with lactation. With adjustments, the MIRIS might provide a helpful tool for individualised fortification. PMID- 26833712 TI - Macrophage cell death in microbial infections. AB - Macrophages can respond to microbial infections with programmed cell death. The major cell death pathways of apoptosis, pyroptosis and necroptosis are tightly regulated to ensure adequate immune reactions to virulent and persistent invaders. Macrophage death eliminates the replicative niche of intracellular pathogens and induces immune attack. Not surprisingly, successful pathogens have evolved strategies to modulate macrophage cell death pathways to enable microbial survival and replication. Uncontrolled macrophage death can also lead to tissue damage, which may augment bacterial dissemination and pathology. In this review, we highlight how pathogens hijack macrophage cell death signals to promote microbial survival and immune evasion. PMID- 26833711 TI - Suicide Risk Documented During Veterans' Last Veterans Affairs Health Care Contacts Prior to Suicide. AB - A total of 295 veterans who died by suicide in 2009 across 11 states and received Veterans Affairs (VA) health care in the 6 months prior to death were identified. The suicide risk factors documented and the care received at these veterans' last VA contacts are described, and the study explores whether veterans present differently to VA care (i.e., different risk factors documented or different care settings accessed) based on the proximity of their last contact to suicide. Many veterans were seen in primary care (n = 136; 46%) for routine follow-up (n = 168; 57%). Fifty-three (18%) were assessed for suicidal thoughts; 20 (38%) of whom endorsed such thoughts. Although higher frequencies of some risk factors at last contacts more proximal to suicide compared to those more distal were observed, findings overall highlight the challenges clinicians face detecting enhanced risk prior to suicide. PMID- 26833713 TI - Population-based assessment of chronic myeloid leukemia in Sweden: striking increase in survival and prevalence. AB - The clinical outcome for patients with chronic myeloid leukemia (CML) has improved dramatically following the introduction of tyrosine kinase inhibitors. An improved survival, combined with a constant incidence, is expected to increase the prevalence of CML. However, data on the prevalence of CML remain scarce. We examined the overall and relative (age and gender matched) survival and assessed the past, present, and projected future prevalence of CML in Sweden. Data on all patients diagnosed with CML between 1970 and 2012 were retrieved from the Swedish Cancer Register and the Swedish Cause of Death Register. The 5-year overall survival increased from 0.18 to 0.82, during the observed time period. Between 2006 and 2012, the 5-year relative survival was close to normal for 40-year-old, but considerably lower for 80-year-old CML patients. The observed prevalence tripled from 1985 to 2012, from 3.9 to 11.9 per 100 000 inhabitants. Assuming no further improvements in relative survival, the prevalence is projected to further increase by 2060 to 22.0 per 100 000 inhabitants (2587 persons in Sweden). The projected dramatic increase in CML prevalence has major medical and health economic implications and needs to be considered in planning how to organize future care of CML patients. PMID- 26833714 TI - Design of Novel Visible Light Active Photocatalyst Materials: Surface Modified TiO2. AB - Work on the design of new TiO2 based photocatalysts is described. The key concept is the formation of composite structures through the modification of anatase and rutile TiO2 with molecular-sized nanoclusters of metal oxides. Density functional theory (DFT) level simulations are compared with experimental work synthesizing and characterizing surface modified TiO2 . DFT calculations are used to show that nanoclusters of metal oxides such as TiO2 , SnO/SnO2 , PbO/PbO2 , ZnO and CuO are stable when adsorbed at rutile and anatase surfaces, and can lead to a significant red shift in the absorption edge which will induce visible light absorption; this is the first requirement for a useful photocatalyst. The origin of the red shift and the fate of excited electrons and holes are determined. For p-block metal oxides the oxidation state of Sn and Pb can be used to modify the magnitude of the red shift and its mechanism. Comparisons of recent experimental studies of surface modified TiO2 that validate our DFT simulations are described. These nanocluster-modified TiO2 structures form the basis of a new class of photocatalysts which will be useful in oxidation reactions and with a correct choice of nanocluster modified can be applied to other reactions. PMID- 26833715 TI - Respiratory Function Under Intrathecal Baclofen Therapy in Patients With Spastic Tetraplegia. AB - OBJECTIVES: Intrathecal baclofen (ITB) therapy is an effective treatment for patients with severe spasticity. However, the effect of ITB therapy on respiratory function has not been reported in detail. In this study we quantitatively analyzed the effects of ITB on the respiratory function of patients with spastic tetraplegia. METHODS: We retrospectively reviewed 23 patients who were administrated ITB therapy from January 2009 to December 2012. Six of these 23 patients, who had spastic tetraplegia and were able to undergo spirometric testing, were included this study. The spasticity derived from cervical spinal cord injury in four patients and cerebral palsy (CP) in two patients. Patients' Ashworth Scale scores and spirometer measurements obtained before and 1-6 months after the start of ITB therapy were evaluated and compared. RESULTS: Before ITB therapy, %FVC of all six patients was below 80%, and a restrictive respiratory disorder was diagnosed in five patients and a combined respiratory disorder in one patient. Ashworth Scale scores for both the lower and upper extremities improved significantly with ITB therapy. Forced vital capacity (FVC), %FVC, and forced expiratory volume at one sec also improved significantly with ITB therapy. CONCLUSIONS: Respiratory disorders were indeed present in our SCI and CP patients with spastic tetraplegia, and the respiratory function of these patients improved with ITB therapy. Our results suggest that ITB therapy is safe and efficacious in patients with spastic tetraplegia and respiratory dysfunction. PMID- 26833717 TI - Serum calcium may not accurately predict intradialytic calcium mass transfer. PMID- 26833716 TI - Conserved structure of Snu13 from the highly reduced spliceosome of Cyanidioschyzon merolae. AB - Structural and functional analysis of proteins involved in pre-mRNA splicing is challenging because of the complexity of the splicing machinery, known as the spliceosome. Bioinformatic, proteomic, and biochemical analyses have identified a minimal spliceosome in the red alga Cyanidioschyzon merolae. This spliceosome consists of only 40 core proteins, compared to ~ 70 in S. cerevisiae (yeast) and ~ 150 in humans. We report the X-ray crystallographic analysis of C. merolae Snu13 (CmSnu13), a key component of the assembling spliceosome, and present evidence for conservation of Snu13 function in this algal splicing pathway. The near identity of CmSnu13's three-dimensional structure to yeast and human Snu13 suggests that C. merolae should be an excellent model system for investigating the structure and function of the conserved core of the spliceosome. PMID- 26833718 TI - Procoagulant changes in fibrin clot structure in patients with cirrhosis are associated with oxidative modifications of fibrinogen. AB - Essentials Patients with cirrhosis have hemostatic changes, which may contribute to a risk of thrombosis. This in vitro study compares clot formation and structure between patients and healthy subjects. Clot formation is delayed in patients; ultimately, however, clot permeability is decreased. The thrombogenic structure of fibrin clots may contribute to the thrombotic risk in cirrhosis. ABSTRACT: Background and Objectives Patients with cirrhosis can be at risk of thrombotic complications due to an imbalance between hemostatic components. However, little is known on how the disease affects clot generation or how alterations in the structure of fibrin clots may affect the hemostatic function of these patients. Methods We investigated the formation and structure of clots generated with plasma and purified fibrinogen of 42 patients with cirrhosis. Clots generated with plasma and fibrinogen of 29 healthy volunteers were studied for comparison. Clot formation and structure were assessed by turbidity, permeation studies, confocal laser and scanning electron microscopy (SEM). The extent of fibrinogen oxidation was assessed by measuring the carbonyl content of purified fibrinogen samples. Results Tissue factor and thrombin-induced clotting of plasma was delayed in patients. The clotting rate was also decreased, but change in turbidity, fibrin density and fiber thickness were largely comparable to healthy volunteers. Conversely, clot permeability was significantly decreased in patients. When clots were generated with purified fibrinogen, differences in clot formation and structure similar to those in plasma were found. The carbonyl content was increased in patient fibrinogen and correlated with disease severity and clot permeability. Conclusions Delayed clot formation in cirrhosis ultimately results in decreased clot permeability. Similar alterations in clots generated with purified fibrinogen suggest that modifications of the molecule are (partly) responsible. Taken together, these findings are indicative of hypercoagulable features of clots of patients with cirrhosis, which may explain the increased risk of thrombosis associated with this condition. PMID- 26833719 TI - Metabolic effects of eradicating breath methane using antibiotics in prediabetic subjects with obesity. AB - OBJECTIVE: Methanogens colonizing the human gut produce methane and influence host metabolism. This study examined metabolic parameters in methane-producing subjects before and after antibiotic treatment. METHODS: Eleven prediabetic methane-positive subjects (9F, 2M) with obesity (BMI 35.17 +/- 7.71 kg/m(2) ) aged 47 +/- 9 years were recruited. Subjects underwent breath testing, symptom questionnaire, oral glucose tolerance test (OGTT), lipid profile, and stool Methanobrevibacter smithii levels, gastric transit, and energy utilization analyses. After a 10-day antibiotic therapy (neomycin 500 mg bid/rifaximin 550 mg tid), all testing was repeated. RESULTS: Baseline stool M. smithii levels correlated with breath methane (R = 0.7, P = 0.05). Eight subjects (73%) eradicated breath methane and showed reduced stool M. smithii (P = 0.16). After therapy, methane-eradicated subjects showed significant improvements in low density lipoprotein (LDL) (P = 0.028), total cholesterol (P = 0.01), and insulin levels on OGTT (P = 0.05 at 120 minutes), lower blood glucose levels on OGTT (P = 0.054 at 90 minutes), significant reductions in bloating (P = 0.018) and straining (P = 0.059), and a trend toward lower stool dry weight. No changes were detected in gastric emptying time or energy harvest. CONCLUSIONS: Breath methane eradication and M. smithii reduction are associated with significant improvements in total cholesterol, LDL, and insulin levels and with lower glucose levels in prediabetic subjects with obesity. The underlying mechanisms require further elucidation. PMID- 26833720 TI - Identification of genes involved in rice seed priming in the early imbibition stage. AB - Phase II of seed imbibition is a critical process during seed priming. To identify genes involved in rice seed priming, the altered proteins between the dry and imbibed (24 h) seeds were compared using a two-dimensional gel electrophoresis system in this study. Ten significantly changed proteins (fold change >= twofold; P < 0.01) were successfully identified, which could be categorised as carbohydrate and protein biosynthesis and metabolism-related, signalling-related, storage and stress-related proteins. A meta-analysis indicated that the highest expression of the identified genes was at the milk and dough stages and in the endosperm tissue. Quantitative real-time PCR analysis showed that there was significant variation in gene expression (except FAD dependent oxidoreductase) in embryos during seed priming (0-48 h). The expression of genes associated with stress appeared at the early imbibition stage, while those associated with carbohydrate metabolism, protein synthesis and signalling increased at the late imbibition stage. Three identified proteins (glucose-1 phosphate adenylyltransferase large subunit, aminotransferase and prolamin precursor) had similar transcript and protein expression patterns in embryos. Based on phenotype and gene expression, the optimal stop time for seed priming is 24 h, when these three genes have relatively low expression, followed by significant induction during imbibition in embryos. These three genes are ideal candidate biomarkers for rice seed priming. PMID- 26833721 TI - Injection scheme for intravitreal bevacizumab therapy for macular oedema due to central retinal vein occlusion: results of a multicentre study. PMID- 26833722 TI - The regenerative role of adipose-derived stem cells (ADSC) in plastic and reconstructive surgery. AB - The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in plastic and reconstructive surgery. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. Adult mesenchymal stem cells appear to be an ideal stem cell population for practical regenerative medicine. Among these cells, adipose-derived stem cells (ADSC) have the potential to differentiate the mesenchymal, ectodermal and endodermal lineages and are easy to harvest. Additionally, adipose tissue yields a high number of ADSC per volume of tissue. Based on this background knowledge, the purpose of this review is to summarise and describe the proliferation and differentiation capacities of ADSC together with current preclinical data regarding the use of ADSC as regenerative tools in plastic and reconstructive surgery. PMID- 26833723 TI - Corrigendum. PMID- 26833724 TI - Do Statins Attenuate Postoperative Atrial Fibrillation in Isolated Heart Valve Surgery? PMID- 26833725 TI - gammadeltaT Cells and Related Diseases. AB - Discovered 30 years ago, gammadeltaT cells remain an enigmatic T-cell subset. Although they account for a small portion of the total human circulating T-cell pool, their associations with other immune cells and their potential regulatory roles in related diseases have been explored but still require further investigation. gammadeltaT cells which are MHC-unrestricted innate-like lymphocytes with more unique antigen receptors than alphabetaT cells and B cells are considered to bridge innate and adaptive immunity. They have APC functions and initiate adaptive immunity. Due to their distribution in specific tissues, secretion of Th1-, Th2-, and Th17-type cytokines, and other characteristics, they are involved in a variety of physiology and pathology processes. They are barometers in HIV infection. However, different gammadeltaT cell subsets play opposing roles in HBV infections, autoimmune diseases, and several types of tumors. Moreover, decidual gammadeltaT cells have protective roles during pregnancies by synthesizing several cytokines. This emerging evidence provides an improved understanding of the immune mechanism of infection, autoimmunity, cancer, and other related disorders and better insights regarding the potential roles of gammadeltaT cells in immunological therapeutic strategies. PMID- 26833726 TI - Feeding the germline. AB - Nucleotides are required in order to replicate DNA in the developing germline. Here, Chi and colleagues (pp. 307-320) have used Caernohabditis elegans to identify a GLP-1-dependent checkpoint that senses food (bacterially)-supplied nucleotide levels, arresting reproductive development in the absence of sufficient nucleotide supplies. PMID- 26833727 TI - Structural basis for human PRDM9 action at recombination hot spots. AB - The multidomain zinc finger (ZnF) protein PRDM9 (PRD1-BF1-RIZ1 homologous domain containing 9) is thought to influence the locations of recombination hot spots during meiosis by sequence-specific DNA binding and trimethylation of histone H3 Lys4. The most common variant of human PRDM9, allele A (hPRDM9A), recognizes the consensus sequence 5'-NCCNCCNTNNCCNCN-3'. We cocrystallized ZnF8-12 of hPRDM9A with an oligonucleotide representing a known hot spot sequence and report the structure here. ZnF12 was not visible, but ZnF8-11, like other ZnF arrays, follows the right-handed twist of the DNA, with the alpha helices occupying the major groove. Each alpha helix makes hydrogen-bond (H-bond) contacts with up to four adjacent bases, most of which are purines of the complementary DNA strand. The consensus C:G base pairs H-bond with conserved His or Arg residues in ZnF8, ZnF9, and ZnF11, and the consensus T:A base pair H-bonds with an Asn that replaces His in ZnF10. Most of the variable base pairs (N) also engage in H bonds with the protein. These interactions appear to compensate to some extent for changes from the consensus sequence, implying an adaptability of PRDM9 to sequence variations. We investigated the binding of various alleles of hPRDM9 to different hot spot sequences. Allele C was found to bind a C-specific hot spot with higher affinity than allele A bound A-specific hot spots, perhaps explaining why the former is dominant in A/C heterozygotes. Allele L13 displayed higher affinity for several A-specific sequences, allele L9/L24 displayed lower affinity, and allele L20 displayed an altered sequence preference. These differences can be rationalized structurally and might contribute to the variation observed in the locations and activities of meiotic recombination hot spots. PMID- 26833728 TI - The evolutionary turnover of recombination hot spots contributes to speciation in mice. AB - Meiotic recombination is required for the segregation of homologous chromosomes and is essential for fertility. In most mammals, the DNA double-strand breaks (DSBs) that initiate meiotic recombination are directed to a subset of genomic loci (hot spots) by sequence-specific binding of the PRDM9 protein. Rapid evolution of the DNA-binding specificity of PRDM9 and gradual erosion of PRDM9 binding sites by gene conversion will alter the recombination landscape over time. To better understand the evolutionary turnover of recombination hot spots and its consequences, we mapped DSB hot spots in four major subspecies of Mus musculus with different Prdm9 alleles and in their F1 hybrids. We found that hot spot erosion governs the preferential usage of some Prdm9 alleles over others in hybrid mice and increases sequence diversity specifically at hot spots that become active in the hybrids. As crossovers are disfavored at such hot spots, we propose that sequence divergence generated by hot spot turnover may create an impediment for recombination in hybrids, potentially leading to reduced fertility and, eventually, speciation. PMID- 26833729 TI - A gain-of-function senescence bypass screen identifies the homeobox transcription factor DLX2 as a regulator of ATM-p53 signaling. AB - Senescence stimuli activate multiple tumor suppressor pathways to initiate cycle arrest and a differentiation program characteristic of senescent cells. We performed a two-stage, gain-of-function screen to select for the genes whose enhanced expression can bypass replicative senescence. We uncovered multiple genes known to be involved in p53 and Rb regulation and ATM regulation, two components of the CST (CTC1-STN1-TEN1) complex involved in preventing telomere erosion, and genes such as REST and FOXO4 that have been implicated in aging. Among the new genes now implicated in senescence, we identified DLX2, a homeobox transcription factor that has been shown to be required for tumor growth and metastasis and is associated with poor cancer prognosis. Growth analysis showed that DLX2 expression led to increased cellular replicative life span. Our data suggest that DLX2 expression reduces the protein components of the TTI1/TTI2/TEL2 complex, a key complex required for the proper folding and stabilization of ATM and other members of the PIKK (phosphatidylinositol 3-kinase-related kinase) family kinase, leading to reduced ATM-p53 signaling and senescence bypass. We also found that the overexpression of DLX2 exhibited a mutually exclusive relationship with p53 alterations in cancer patients. Our functional screen identified novel players that may promote tumorigenesis by regulating the ATM-p53 pathway and senescence. PMID- 26833730 TI - Nucleotide levels regulate germline proliferation through modulating GLP-1/Notch signaling in C. elegans. AB - Animals alter their reproductive programs to accommodate changes in nutrient availability, yet the connections between known nutrient-sensing systems and reproductive programs are underexplored, and whether there is a mechanism that senses nucleotide levels to coordinate germline proliferation is unknown. We established a model system in which nucleotide metabolism is perturbed in both the nematode Caenorhabditis elegans (cytidine deaminases) and its food (Escherichia coli); when fed food with a low uridine/thymidine (U/T) level, germline proliferation is arrested. We provide evidence that this impact of U/T level on the germline is critically mediated by GLP-1/Notch and MPK-1/MAPK, known to regulate germline mitotic proliferation. This germline defect is suppressed by hyperactivation of glp-1 or disruption of genes downstream from glp-1 to promote meiosis but not by activation of the IIS or TORC1 pathways. Moreover, GLP-1 expression is post-transcriptionally modulated by U/T levels. Our results reveal a previously unknown nucleotide-sensing mechanism for controlling reproductivity. PMID- 26833732 TI - Patient sues over CMPA's ability to "insure". PMID- 26833731 TI - MLL1 is essential for the senescence-associated secretory phenotype. AB - Oncogene-induced senescence (OIS) and therapy-induced senescence (TIS), while tumor-suppressive, also promote procarcinogenic effects by activating the DNA damage response (DDR), which in turn induces inflammation. This inflammatory response prominently includes an array of cytokines known as the senescence associated secretory phenotype (SASP). Previous observations link the transcription-associated methyltransferase and oncoprotein MLL1 to the DDR, leading us to investigate the role of MLL1 in SASP expression. Our findings reveal direct MLL1 epigenetic control over proproliferative cell cycle genes: MLL1 inhibition represses expression of proproliferative cell cycle regulators required for DNA replication and DDR activation, thus disabling SASP expression. Strikingly, however, these effects of MLL1 inhibition on SASP gene expression do not impair OIS and, furthermore, abolish the ability of the SASP to enhance cancer cell proliferation. More broadly, MLL1 inhibition also reduces "SASP-like" inflammatory gene expression from cancer cells in vitro and in vivo independently of senescence. Taken together, these data demonstrate that MLL1 inhibition may be a powerful and effective strategy for inducing cancerous growth arrest through the direct epigenetic regulation of proliferation-promoting genes and the avoidance of deleterious OIS- or TIS-related tumor secretomes, which can promote both drug resistance and tumor progression. PMID- 26833733 TI - Evidence for transmissibility of Alzheimer disease pathology: Cause for concern? PMID- 26833734 TI - Debate sparked over pharma-funded CME. PMID- 26833735 TI - Maybe there is no such thing as bronchiolitis. PMID- 26833736 TI - No standards: medicolegal investigation of deaths. PMID- 26833737 TI - Quebec's new e-health records may spur change. PMID- 26833738 TI - A 19-year-old woman with sickle cell disease and pain. PMID- 26833739 TI - Urinary tract infection in older adults in long-term care facilities. PMID- 26833740 TI - The catalytic effect of the NH3 base on the chemical events in the caryolene forming carbocation cascade. AB - Caryolene formation occur asynchronously in a concerted way through carbocationic rearrangements involving the generation of a secondary or a tertiary carbocation whether the reaction proceeds in the absence or in the presence of NH3 , respectively. Both caryolene formation mechanisms are analyzed within the general framework of the reaction force; the reaction force constant is used to gain insights into the synchronicity of the mechanisms and the reaction electronic flux helps to characterize the electronic activity taking place during the reaction. DFT calculations at the B3LYP/6-31+G(d,p) level show a clear difference in the mechanisms of the base promoted or base free caryolene formation reactions. PMID- 26833741 TI - Patient-derived xenograft mouse models of pseudomyxoma peritonei recapitulate the human inflammatory tumor microenvironment. AB - Pseudomyxoma peritonei (PMP) is a neoplastic syndrome characterized by peritoneal tumor implants with copious mucinous ascites. The standard of care for PMP patients is aggressive cytoreductive surgery performed in conjunction with heated intraperitoneal chemotherapy. Not all patients are candidates for these procedures and a majority of the patients will have recurrent disease. In addition to secreted mucin, inflammation and fibrosis are central to PMP pathogenesis but the molecular processes that regulate tumor-stromal interactions within the peritoneal tumor microenvironment remain largely unknown. This knowledge is critical not only to elucidate PMP pathobiology but also to identify novel targets for therapy. Here, we report the generation of patient-derived xenograft (PDX) mouse models for PMP and assess the ability of these models to replicate the inflammatory peritoneal microenvironment of human PMP patients. PDX mouse models of low- and high-grade PMP were generated and were of a similar histopathology as human PMP. Cytokines previously shown to be elevated in human PMP were also elevated in PDX ascites. Significant differences in IL-6 and IL 8/KC/MIP2 were seen between human and PDX ascites. Interestingly, these cytokines were mostly secreted by mouse-derived, tumor-associated stromal cells rather than by human-derived PMP tumor cells. Our data suggest that the PMP PDX mouse models are especially suited to the study of tumor-stromal interactions that regulate the peritoneal inflammatory environment in PMP as the tumor and stromal cells in these mouse models are of human and murine origins, respectively. These mouse models are therefore, likely to be useful in vivo surrogates for testing and developing novel therapeutic treatment interventions for PMP. PMID- 26833742 TI - Optimal ATRP-Made Soluble Polymer Supports for Phosphoramidite Chemistry. AB - Soluble polystyrene supports with optimal molecular structures for iterative phosphoramidite chemistry were prepared by atom-transfer radical polymerization (ATRP) and subsequent chain-end modification steps. The controlled radical polymerization of styrene was first performed in the presence of an 9 fluorenylmethoxycarbonyl (Fmoc)-protected amino-functional ATRP initiator. Soluble supports of different molecular weight were prepared. Size-exclusion chromatography and NMR analysis indicated formation of well-defined polymers with controlled chain lengths and narrow dispersity. After synthesis, the bromo omega end group of the ATRP polymer was removed by dehalogenation in the presence of tributyltin hydride, and the Fmoc protecting group of the alpha moiety was subsequently cleaved with piperidine. The resulting alpha-primary amine was afterwards treated with a linker containing a carboxyl group, a cleavable ester site, and a dimethoxytrityl-protected hydroxyl group to afford ideal soluble supports for phosphoramidite chemistry. NMR analysis indicated that these chain end modifications were quantitative. The supports were tested for the synthesis of a non-natural sequence-defined oligophosphates. High-resolution ESI-MS analysis of the cleaved oligomers indicated formation of uniform species, and thus confirmed the efficiency of the ATRP-made soluble polymer supports. In addition, the synthesis of a thymidine-loaded soluble support was achieved. PMID- 26833745 TI - Form and Function in the Evolution of Grammar. AB - This article focuses on claims about the origin and evolution of language from the point of view of the formalist-functionalist debate in linguistics. In linguistics, an account of a grammatical phenomenon is considered "formal" if it accords center stage to the structural properties of that phenomenon, and "functional" if it appeals to the language user's communicative needs or to domain-general human capacities. The gulf between formalism and functionalism has been bridged in language evolution research, in that some leading formalists, Ray Jackendoff for one, appeal to functional mechanisms such as natural selection. In Jackendoff's view, the biological evolution of language has proceeded in stages, each stage improving communicative efficiency. This article calls into question that idea, pointing to the fact that well-understood purely historical processes suffice to explain the emergence of many grammatical properties. However, one central aspect of formalist linguistic theorizing-the idea of the autonomy of syntax-poses a challenge to the idea, central to most functionalist approaches, that the nature of grammar is a product of purely historical (as opposed to biological) evolution. The article concludes with a discussion of the origins of the autonomy of syntax, speculating that it may well have arisen over evolutionary (as opposed to historical) time. PMID- 26833744 TI - Exposure-response analyses of liraglutide 3.0 mg for weight management. AB - AIMS: Liraglutide 3.0 mg, an acylated GLP-1 analogue approved for weight management, lowers body weight through decreased energy intake. We conducted exposure-response analyses to provide important information on individual responses to given drug doses, reflecting inter-individual variations in drug metabolism, absorption and excretion. METHODS: We report efficacy and safety responses across a wide range of exposure levels, using data from one phase II (liraglutide doses 1.2, 1.8, 2.4 and 3.0 mg), and two phase IIIa [SCALE Obesity and Prediabetes (3.0 mg); SCALE Diabetes (1.8; 3.0 mg)] randomized, placebo controlled trials (n = 4372). RESULTS: There was a clear exposure-weight loss response. Weight loss increased with greater exposure and appeared to level off at the highest exposures associated with liraglutide 3.0 mg in most individuals, but did not fully plateau in men. In individuals with overweight/obesity and comorbid type 2 diabetes, there was a clear exposure-glycated haemoglobin (HbA1c) relationship. HbA1c reduction increased with higher plasma liraglutide concentration (plateauing at ~21 nM); however, for individuals with baseline HbA1c >8.5%, HbA1c reduction did not fully plateau. No exposure-response relationship was identified for any safety outcome, with the exception of gastrointestinal adverse events (AEs). Individuals with gallbladder AEs, acute pancreatitis or malignant/breast/benign colorectal neoplasms did not have higher liraglutide exposure compared with the overall population. CONCLUSIONS: These analyses support the use of liraglutide 3.0 mg for weight management in all subgroups investigated; weight loss increased with higher drug exposure, with no concomitant deterioration in safety/tolerability besides previously known gastrointestinal side effects. PMID- 26833743 TI - Insulin-like growth factor 1 has multisystem effects on foetal and preterm infant development. AB - Poor postnatal growth after preterm birth does not match the normal rapid growth in utero and is associated with preterm morbidities. Insulin-like growth factor 1 (IGF-1) axis is the major hormonal mediator of growth in utero, and levels of IGF 1 are often very low after preterm birth. We reviewed the role of IGF-1 in foetal development and the corresponding preterm perinatal period to highlight the potential clinical importance of IGF-1 deficiency in preterm morbidities. CONCLUSION: There is a rationale for clinical trials to evaluate the potential benefits of IGF-1 replacement in very preterm infants. PMID- 26833746 TI - Long noncoding RNA, tissue differentiation-inducing nonprotein coding RNA is upregulated and promotes development of esophageal squamous cell carcinoma. AB - Esophageal squamous cell carcinoma (ESCC) is one of the major causes of cancer death worldwide, especially in Eastern Asia. Due to the poor prognosis, it is necessary to further dissect the underlying mechanisms and explore therapeutic targets of ESCC. Recently, studies show that long noncoding RNAs (lncRNAs) have critical roles in diverse biological processes, including tumorigenesis. Increasing evidence indicates that some lncRNAs are widely involved in the development and progression of ESCC, such as HOTAIR, SPRY4-IT1 and POU3F3. An emerging lncRNA, tissue differentiation-inducing nonprotein coding RNA (TINCR), has been studied in human cutaneous squamous cell carcinoma and has critical biological function, but its role in ESCC remains unknown. Here, we evaluated the expression profile of TINCR and its biological function in ESCC. In a cohort of 56 patients, TINCR was significantly overexpressed in ESCC tissues compared with paired adjacent normal tissues. Further, in vitro silencing TINCR via small interfering RNA (siRNA) inhibited the proliferation, migration and invasion of ESCC cells. Meantime, siRNA treatment induced apoptosis and blocked the progression of cell cycle. Taken together, our study suggests that TINCR promotes proliferation, migration and invasion of ESCC cells, acting as a potential oncogene of ESCC. PMID- 26833747 TI - Device Engineered Organic Transistors for Flexible Sensing Applications. AB - Organic thin-film transistors (OFETs) represent a promising candidate for next generation sensing applications because of the intrinsic advantages of organic semiconductors. The development of flexible sensing devices has received particular interest in the past few years. The recent efforts of developing OFETs for sensitive and specific flexible sensors are summarized from the standpoint of device engineering. The tuning of signal transduction and signal amplification are highlighted based on an overview of active-layer thickness modulation, functional receptor implantation and device geometry optimization. PMID- 26833750 TI - Dietary folate, one-carbon metabolism-related genes, and gastric cancer risk in Korea. AB - SCOPE: We evaluated the interactions between polymorphisms involved in one-carbon metabolism-related genes and dietary folate intake in gastric cancer risk within the Korean population through a hospital-based case-control study. METHODS AND RESULTS: A total of 542 controls and 271 cases were included. Genotype data were selected from data produced by the Affymetrix Axiom((r)) Exome 319 Array. We considered seven single nucleotide polymorphisms (SNPs) of five genes whose SNPs are located in the coding region with a minor allele frequency > 5%: MTHFR (G1793A, A1298C, C677T), MTR A2756G, MTRR A66G, SHMT1 C1420T, and SLC19A1 G80A. Our study found that MTR A2756G was associated with a decreased gastric cancer risk. MTHFR G1793A showed a statistically significant interaction between dietary folate intake and gastric cancer. CONCLUSION: Our results suggest that MTR A2756G is significantly associated with gastric cancer risk, and that MTHFR G1793A statistically interacts with dietary folate intake. Our findings indicate that gene-folate interactions may contribute to gastric cancer risk. PMID- 26833752 TI - Low dose heparin lock (1000 U/mL) maintains tunnelled hemodialysis catheter patency when compared with high dose heparin (5000 U/mL): A randomised controlled trial. AB - Introduction Heparin is commonly used after hemodialysis treatments as a locking solution to prevent catheter thrombosis. The comparative efficacy and safety of different heparin concentrations to maintain catheter patency has been previously reported in retrospective studies. We conducted a prospective, randomised, controlled study of 1000 U/mL heparin (low dose) versus 5000 U/mL heparin (high dose) locking solution to maintain patency of tunnelled catheters. Methods One hundred patients receiving chronic, unit-based hemodialysis with newly placed tunnelled hemodialysis catheters (less than 1 week) were randomly assigned to either a low dose (n = 48) or high dose heparin (n=52). The primary intention-to treat analysis examined time to malfunction in both groups over a 90 day period. A secondary analysis compared baseline patient characteristics in relation to catheter malfunction. Findings Overall rate of catheter patency loss was 32% of catheters by 90 days. There was no significant difference in time to malfunction of catheters locked with low dose or high dose heparin (P = 0.5770). Time to catheter malfunction was not associated with diabetic, hypertensive or smoking status. There was no difference in mean delivered blood flow rate, venous and arterial pressure, and dialysis adequacy between low dose and high dose groups. No patient suffered a hemorrhagic complication requiring hospitalisation during the study period. Discussion Low dose heparin is adequate to maintain tunnelled hemodialysis catheter patency when compared with high dose heparin. The study also suggests that there is no relationship between catheter malfunction and diabetic, hypertensive or smoking status. PMID- 26833751 TI - Biochemical characterization of two haloalkane dehalogenases: DccA from Caulobacter crescentus and DsaA from Saccharomonospora azurea. AB - Two putative haloalkane dehalogenases (HLDs) of the HLD-I subfamily, DccA from Caulobacter crescentus and DsaA from Saccharomonospora azurea, have been identified based on sequence comparisons with functionally characterized HLD enzymes. The two genes were synthesized, functionally expressed in E. coli and shown to have activity toward a panel of haloalkane substrates. DsaA has a moderate activity level and a preference for long (greater than 3 carbons) brominated substrates, but little activity toward chlorinated alkanes. DccA shows high activity with both long brominated and chlorinated alkanes. The structure of DccA was determined by X-ray crystallography and was refined to 1.5 A resolution. The enzyme has a large and open binding pocket with two well-defined access tunnels. A structural alignment of HLD-I subfamily members suggests a possible basis for substrate specificity is due to access tunnel size. PMID- 26833753 TI - Quantifying the proportion of deaths due to body mass index- and waist circumference-defined obesity. AB - OBJECTIVE: To determine the risk of mortality associated with and quantify the deaths attributable to combinations of body mass index (BMI) and waist circumference (WC). METHODS: This study included 41,439 participants. For the hazard ratio (HR) calculation, adiposity categories were defined as: BMI(N) /WC(N) , BMI(N) /WC(O) , BMI(O) /WC(N) , and BMI(O) /WC(O) (N = non-obese, O = obese). For the population attributable fraction analysis, obesity was classified as: (i) obese by BMI and/or WC; (ii) obese by BMI; and (iii) obese by WC. Mortality data was complete to the end of 2012. RESULTS: The prevalence of BMI(N) /WC(N) , BMI(N) /WC(O) , BMI(O) /WC(N) , and BMI(O) /WC(O) was 73%, 6%, 6%, and 15%, respectively. There was an increased risk of all-cause and cardiovascular disease (CVD) mortality in those with BMI(N) /WC(O) (HR (95% CI) 1.2 (1.2, 1.3) and 1.3 (1.1, 1.6)) and BMI(O) /WC(O) (1.3 (1.3, 1.4) and 1.7 (1.5, 1.9)) compared to those with BMI(N) /WC(N) . The estimated proportion of all-cause and CVD mortality attributable to obesity defined using WC or using BMI and/or WC was higher compared to obesity defined using BMI. CONCLUSIONS: Current population obesity monitoring misses those with BMI(N) /WC(O) who are at increased risk of mortality. By targeting reductions in population WC, the potential exists to prevent more deaths in the population than if we continue to target reductions in BMI alone. PMID- 26833754 TI - Photosynthetic limitation of several representative subalpine species in the Catalan Pyrenees in summer. AB - Information on the photosynthetic process and its limitations is essential in order to predict both the capacity of species to adapt to conditions associated with climate change and the likely changes in plant communities. Considering that high-mountain species are especially sensitive, three species representative of subalpine forests of the Central Catalan Pyrenees: mountain pine (Pinus uncinata Mill.), birch (Betula pendula Roth) and rhododendron (Rhododendron ferrugineum L.) were studied under conditions associated with climate change, such as low precipitation, elevated atmospheric [CO2 ] and high solar irradiation incident at Earth's surface, in order to detect any photosynthetic limitations. Short-term high [CO2 ] increased photosynthesis rates (A) and water use efficiency (WUE), especially in birch and mountain pine, whereas stomatal conductance (gs ) was not altered in either species. Birch showed photosynthesis limitation through stomatal closure related to low rainfall, which induced photoinhibition and early foliar senescence. Rhododendron was especially affected by high irradiance, showing early photosynthetic saturation in low light, highest chlorophyll content, lowest gas exchange rates and least photoprotection. Mountain pine had the highest A, photosynthetic capacity (Amax ) and light-saturated rates of net CO2 assimilation (Asat ), which were maintained under reduced precipitation. Furthermore, maximum quantum yield (Fv /Fm ), thermal energy dissipation, PRI and SIPI radiometric index, and ascorbate content indicated improved photoprotection with respect to the other two species. However, maximum velocity of carboxylation of RuBisco (Vcmax ) indicated that N availability would be the main photosynthetic limitation in this species. PMID- 26833755 TI - Congenital anomalies of the kidney and the urinary tract: A murmansk county birth registry study. AB - BACKGROUND: Congenital anomalies of the kidney and the urinary tract (CAKUTs) are relatively common birth defects. The combined prevalence in Europe was 3.3 per 1000 in 2012. The risk factors for these anomalies are not clearly identified. The aims of our study were to calculate the birth prevalences of urinary malformations in Murmansk County during 2006 to 2011 and to investigate related prenatal risk factors. METHODS: The Murmansk County Birth Registry was the primary source of information and our study included 50,936 singletons in the examination of structure, prevalence and proportional distribution of CAKUTs. The multivariate analyses of risk factors involved 39,322 newborns. RESULTS: The prevalence of CAKUTs was 4.0 per 1000 newborns (95% confidence interval [CI], 3.4 4.5) and did not change during the study period. The most prevalent malformation was congenital hydronephrosis (14.2% of all cases). Diabetes mellitus or gestational diabetes (odds ratio [OR] = 4.77; 95% CI, 1.16-19.65), acute infections while pregnant (OR = 1.83; 95% CI, 1.14-2.94), the use of medication during pregnancy (OR = 2.03; 95% CI, 1.44-2.82), and conception during the summer (OR = 1.75; 95% CI 1.15-2.66) were significantly associated with higher risk of CAKUTs. CONCLUSION: The overall fourfold enhancement of the occurrence of urinary malformations in Murmansk County for the 2006 to 2011 period showed little annual dependence. During pregnancy, use of medications, infections, pre-existing diabetes mellitus, or gestational diabetes were associated with increased risk of these anomalies, as was conception during summer. Our findings have direct applications in improving prenatal care in Murmansk County and establishing targets for prenatal screening and women's consultations. PMID- 26833756 TI - When the Spatial and Ideological Collide: Metaphorical Conflict Shapes Social Perception. AB - In the present article, we introduce the concept of metaphorical conflict-a conflict between the concrete and abstract aspects of a metaphor. We used the association between the concrete (spatial) and abstract (ideological) components of the political left-right metaphor to demonstrate that metaphorical conflict has marked implications for cognitive processing and social perception. Specifically, we showed that creating conflict between a spatial location and a metaphorically linked concept reduces perceived differences between the attitudes of partisans who are generally viewed as possessing fundamentally different worldviews (Democrats and Republicans). We further demonstrated that metaphorical conflict reduces perceived attitude differences by creating a mind-set in which categories are represented as possessing broader boundaries than when concepts are metaphorically compatible. These results suggest that metaphorical conflict shapes social perception by making members of distinct groups appear more similar than they are generally thought to be. These findings have important implications for research on conflict, embodied cognition, and social perception. PMID- 26833757 TI - Does Seeing Faces of Young Black Boys Facilitate the Identification of Threatening Stimuli? AB - Pervasive stereotypes linking Black men with violence and criminality can lead to implicit cognitive biases, including the misidentification of harmless objects as weapons. In four experiments, we investigated whether these biases extend even to young Black boys (5-year-olds). White participants completed sequential priming tasks in which they categorized threatening and nonthreatening objects and words after brief presentations of faces of various races (Black and White) and ages (children and adults). Results consistently revealed that participants had less difficulty (i.e., faster response times, fewer errors) identifying threatening stimuli and more difficulty identifying nonthreatening stimuli after seeing Black faces than after seeing White faces, and this racial bias was equally strong following adult and child faces. Process-dissociation-procedure analyses further revealed that these effects were driven entirely by automatic (i.e., unintentional) racial biases. The collective findings suggest that the perceived threat commonly associated with Black men may generalize even to young Black boys. PMID- 26833758 TI - Orosomucoid (ORM) as a Potential Biomarker for the Diagnosis of Chronic Fatigue Syndrome (CFS). PMID- 26833759 TI - Delayed grafting for banked skin graft in lymph node flap transfer. AB - Over the last decade, lymph node flap (LNF) transfer has turned out to be an effective method in the management of lymphoedema of extremities. Most of the time, the pockets created for LNF cannot be closed primarily and need to be resurfaced with split thickness skin grafts. Partial graft loss was frequently noted in these cases. The need to prevent graft loss on these iatrogenic wounds made us explore the possibility of attempting delayed skin grafting. We have herein reported our experience with delayed grafting with autologous banked split skin grafts in cases of LNF transfer for lymphoedema of the extremities. Ten patients with International Society of Lymphology stage II-III lymphoedema of upper or lower extremity were included in this study over an 8-month period. All patients were thoroughly evaluated and subjected to lymph node flap transfer. The split skin graft was harvested and banked at the donor site, avoiding immediate resurfacing over the flap. The same was carried out in an aseptic manner as a bedside procedure after confirming flap viability and allowing flap swelling to subside. Patients were followed up to evaluate long-term outcomes. Flap survival was 100%. Successful delayed skin grafting was done between the 4th and 6th post operative day as a bedside procedure under local anaesthesia. The split thickness skin grafts (STSG) takes more than 97%. One patient needed additional medications during the bedside procedure. All patients had minimal post-operative pain and skin graft requirement. The patients were also reported to be satisfied with the final aesthetic results. There were no complications related to either the skin grafts or donor sites during the entire period of follow-up. Delayed split skin grafting is a reliable method of resurfacing lymph node flaps and has been shown to reduce the possibility of flap complications as well as the operative time and costs. PMID- 26833760 TI - Impact of Stewardship Interventions on Antiretroviral Medication Errors in an Urban Medical Center: A 3-Year, Multiphase Study. AB - BACKGROUND: There is a high prevalence of HIV infection in Newark, New Jersey, with University Hospital admitting approximately 600 HIV-infected patients per year. Medication errors involving antiretroviral therapy (ART) could significantly affect treatment outcomes. The goal of this study was to evaluate the effectiveness of various stewardship interventions in reducing the prevalence of prescribing errors involving ART. METHODS: This was a retrospective review of all inpatients receiving ART for HIV treatment during three distinct 6-month intervals over a 3-year period. During the first year, the baseline prevalence of medication errors was determined. During the second year, physician and pharmacist education was provided, and a computerized order entry system with drug information resources and prescribing recommendations was implemented. Prospective audit of ART orders with feedback was conducted in the third year. Analyses and comparisons were made across the three phases of this study. RESULTS: Of the 334 patients with HIV admitted in the first year, 45% had at least one antiretroviral medication error and 38% had uncorrected errors at the time of discharge. After education and computerized order entry, significant reductions in medication error rates were observed compared to baseline rates; 36% of 315 admissions had at least one error and 31% had uncorrected errors at discharge. While the prevalence of antiretroviral errors in year 3 was similar to that of year 2 (37% of 276 admissions), there was a significant decrease in the prevalence of uncorrected errors at discharge (12%) with the use of prospective review and intervention. CONCLUSIONS: Interventions, such as education and guideline development, can aid in reducing ART medication errors, but a committed stewardship program is necessary to elicit the greatest impact. PMID- 26833762 TI - A novel HLA-B allele, HLA-B*35:269. AB - HLA-B*35:269 differs from HLA-B*35:01:01:01, by a single synonymous nucleotide at position 103. PMID- 26833761 TI - A genetic algorithm encoded with the structural information of amino acids and dipeptides for efficient conformational searches of oligopeptides. AB - The genetic algorithm (GA) is an intelligent approach for finding minima in a highly dimensional parametric space. However, the success of GA searches for low energy conformations of biomolecules is rather limited so far. Herein an improved GA scheme is proposed for the conformational search of oligopeptides. A systematic analysis of the backbone dihedral angles of conformations of amino acids (AAs) and dipeptides is performed. The structural information is used to design a new encoding scheme to improve the efficiency of GA search. Local geometry optimizations based on the energy calculations by the density functional theory are employed to safeguard the quality and reliability of the GA structures. The GA scheme is applied to the conformational searches of Lys, Arg, Met-Gly, Lys-Gly, and Phe-Gly-Gly representative of AAs, dipeptides, and tripeptides with complicated side chains. Comparison with the best literature results shows that the new GA method is both highly efficient and reliable by providing the most complete set of the low energy conformations. Moreover, the computational cost of the GA method increases only moderately with the complexity of the molecule. The GA scheme is valuable for the study of the conformations and properties of oligopeptides. (c) 2016 Wiley Periodicals, Inc. PMID- 26833763 TI - Oscillations in the embryonic chick olfactory bulb: initial expression and development revealed by optical imaging with a voltage-sensitive dye. AB - In a previous study, we applied a multiple-site optical recording technique with a voltage-sensitive dye to the embryonic chick olfactory system and showed that functional synaptic transmission in the olfactory bulb was expressed at embryonic 6-7-day stages. It is known that oscillations, i.e. stereotyped sinusoidal neural activity, appear in the olfactory system of various species. The focus of the present study is to determine whether the oscillation is also generated in the embryonic chick olfactory bulb and, if this is the case, when the oscillation appears and how its profiles change during embryogenesis. At the early stages of development (embryonic 6- to 8-day stages), postsynaptic response-related optical signals evoked by olfactory nerve stimulation exhibited a simple monophasic waveform that lasted for a few seconds. At embryonic 9-day stage, the optical signal became multi-phasic, and the oscillatory event was detected in some preparations. The oscillation was restricted to the distal half of the olfactory bulb. As development proceeded, the incidence and duration of the oscillation gradually increased, and the waveform became complicated. In some cases at embryonic 12-day stage, the oscillation lasted for nearly a minute. The frequency of the oscillation increased slightly with development, but it remained in the range of theta oscillation during the 9- to 12-day stages. We discuss the ontogenetic dynamics of the oscillation and the significance of this activity in the developing olfactory bulb. PMID- 26833764 TI - Fused pi-Extended Truxenes via a Threefold Borylation as the Key Step. AB - On the basis of a threefold borylated truxene, which is accessible in high yields by iridium-catalyzed borylation under CH-activation, fused pi-extended truxenes have been synthesized by a two-step method of first Suzuki-Miyaura cross-coupling reaction and subsequent condensation reaction. The mild condensation method tolerates the presence of a variety of functional groups, such as nitro, fluoro, or carboxyl moieties. Furthermore, by using this approach, N- and S-heteroarene analogues become accessible for the first time, as well as larger structures that represent derivatives of precursors for fullerene C60 or buckybowls. The attached tert-butyl groups make all derivatives sufficiently soluble to allow full spectroscopic and electrochemical investigations. Postfunctionalization of selected derivatives for further synthetic applications of the compounds is also presented. PMID- 26833765 TI - Stability in the prevalence of Swedish children who were overweight or obese in 2003 and 2011. AB - AIM: We aimed to explore the prevalence and determinants of overweight including obesity among children in Sweden in 2003 and 2011. METHODS: Two population-based cross-sectional surveys included 7728 and 12 882 12-year-old children in Sweden, and 1198 and 2699 eight-year-old children in Stockholm County, in 2003 and 2011. Weighted prevalence of overweight including obesity and multivariate-adjusted relative risks (RRs) with 95% confidence intervals (CIs) was calculated. RESULTS: In 2011, the overweight prevalence was lower for 12-year-old girls than boys (RR=0.84, CI=0.77-0.92), lower for girls and boys with a higher rather than a lower educated mother (for example, RRgirls =0.76, CI=0.65-0.88), but higher for girls and boys in smaller rather than main cities (RRgirls =1.52, CI=1.28-1.82). There was no difference in overweight prevalence between 2003 and 2011 among the 12-year-old children. However, eight-year-old girls had a lower overweight prevalence in 2011 than in 2003 (RR=0.76, CI=0.59-0.97). The strongest decrease in overweight was among eight-year-old girls with mothers with lower levels of education (RR=0.63, CI=0.47-0.86). CONCLUSION: The prevalence of overweight including obesity was stable among Swedish children between 2003 and 2011. Gradients in the determinants of overweight persisted. There was some evidence of a less steep socio-economic gradient in overweight in eight-year-old girls over time. PMID- 26833767 TI - Is prevention of peritoneal dissemination the next step in the treatment of T4 colon cancer? PMID- 26833768 TI - Lars Pahlman (1946-2015). PMID- 26833772 TI - Conditionals, Context, and the Suppression Effect. AB - Modus ponens is the argument from premises of the form If A, then B and A to the conclusion B (e.g., from If it rained, Alicia got wet and It rained to Alicia got wet). Nearly all participants agree that the modus ponens conclusion logically follows when the argument appears in this Basic form. However, adding a further premise (e.g., If she forgot her umbrella, Alicia got wet) can lower participants' rate of agreement-an effect called suppression. We propose a theory of suppression that draws on contemporary ideas about conditional sentences in linguistics and philosophy. Semantically, the theory assumes that people interpret an indicative conditional as a context-sensitive strict conditional: true if and only if its consequent is true in each of a contextually determined set of situations in which its antecedent is true. Pragmatically, the theory claims that context changes in response to new assertions, including new conditional premises. Thus, the conclusion of a modus ponens argument may no longer be accepted in the changed context. Psychologically, the theory describes people as capable of reasoning about broad classes of possible situations, ordered by typicality, without having to reason about individual possible worlds. The theory accounts for the main suppression phenomena, and it generates some novel predictions that new experiments confirm. PMID- 26833773 TI - Myeloperoxidase anti-neutrophil cytoplasmic antibody affinity is associated with the formation of neutrophil extracellular traps in the kidney and vasculitis activity in myeloperoxidase anti-neutrophil cytoplasmic antibody-associated microscopic polyangiitis. AB - Anti-neutrophil cytoplasmic antibody (ANCA) is associated with small-vessel vasculitis particularly in the kidneys and can induce the formation of neutrophil extracellular traps (NETs) from primed neutrophils. Recently we have reported that the induction of NETs correlates with ANCA affinity for myeloperoxidase (MPO) and disease activity in patients with MPO-ANCA-associated microscopic polyangiitis. To investigate whether MPO-ANCA affinity is associated with the formation of NETs in vivo, we examined the occurrence of NETs in the renal tissues of patients with MPO-ANCA-associated microscopic polyangiitis and ANCA affinity by double immunofluorescence staining for NET components of citrullinated histone, MPO and PAD4 and by ELISA competition with MPO, respectively. We divided 30 MPO-ANCA-associated microscopic polyangiitis patients into 2 groups based on their ANCA affinity levels (IC50 for the high: 0.11 +/- 0.04 ug/mL (Group1) and IC50 for the low: 0.66 +/- 0.24 ug/mL (Group2)). Group1 showed a higher Birmingham vasculitis activity score (15.6 +/- 5.7) and 73% of the patients presented clinically with rapidly progressive glomerulonephritis and histologically with focal/crescentic glomerulonephritis (GN). Group 2 showed a lower Birmingham vasculitis activity score (9.2 +/- 4.9) and 73% of the patients presented clinically with chronic renal failure and histologically with mixed/sclerotic GN. Group 1 showed a much higher occurrence of NETs than Group 2. Our findings indicate that ANCA affinity was associated with the in vivo formation of NETs, which might be involved in the pathophysiology of patients with MPO-ANCA-associated microscopic polyangiitis. PMID- 26833774 TI - Antibacterial resistance in Streptococcus pyogenes (GAS) from healthy carriers and tonsillitis patients and association with antibacterial sale in the Faroe Islands. AB - The aim of this study was to investigate the antibacterial resistance of Streptococcus pyogenes (GAS), and correlate the findings with the sales of erythromycin and tetracycline. General practitioners in the Faroe Islands were recruited to send oropharyngeal swabs. From an ongoing pneumococcal study, nasopharyngeal swabs were sampled from healthy children 0-7 years of age. Erythromycin susceptibility data from Iceland were obtained from the reference laboratory at the Landspitali University Hospital. Susceptibility testing in the Faroe Islands and Iceland was performed according to CLSI methods and criteria. The resistance rate to erythromycin and tetracycline found in patients in the Faroe Islands in 2009/2010 was 6% and 30% respectively. Tetracycline resistance in patients declined significantly from 2009 to 2010 (37-10%, p-value = 0.006 < 0.05) and differed significantly between age groups (p-value = 0.03 < 0.05). In Iceland, there was a peak in erythromycin resistance in 2008 (44%) and a substantial decrease in 2009 (5%). Although the prevalence of erythromycin and tetracycline resistance in the Faroe Islands and Iceland may be associated with antimicrobial use, sudden changes can occur with the introduction of new resistant clones. PMID- 26833778 TI - Acquired reactive perforating collagenosis and pseudoporphyric bullous dermatosis in a hemodialysis patient. AB - Hemodialysis patients present with a broad spectrum of specific and nonspecific skin disorders, which rarely coexist. We report an exceptional case of a hemodialysis patient that developed acquired reactive perforating collagenosis and pseudoporphyric bullous dermatosis on the basis of common skin disorders which include hyperpigmentation, pruritus, xerosis cutis, and Linsday's nails. Interestingly, our patient presented with two unusual but distinctive cutaneous dermopathies on the background of other commonly seen skin alterations. The patient was successfully treated with allopurinol and N-acetylcysteine. Avoidance of potentially triggering factors such as alcohol, sunlight exposure and certain medication was recommended. Thus, increasing clinical awareness, assiduous investigation and early treatment of skin disorders are required to improve the prognosis and quality of life in this patient population. PMID- 26833776 TI - On the satisfaction of backbone-carbonyl lone pairs of electrons in protein structures. AB - Protein structures are stabilized by a variety of noncovalent interactions (NCIs), including the hydrophobic effect, hydrogen bonds, electrostatic forces and van der Waals' interactions. Our knowledge of the contributions of NCIs, and the interplay between them remains incomplete. This has implications for computational modeling of NCIs, and our ability to understand and predict protein structure, stability, and function. One consideration is the satisfaction of the full potential for NCIs made by backbone atoms. Most commonly, backbone-carbonyl oxygen atoms located within alpha-helices and beta-sheets are depicted as making a single hydrogen bond. However, there are two lone pairs of electrons to be satisfied for each of these atoms. To explore this, we used operational geometric definitions to generate an inventory of NCIs for backbone-carbonyl oxygen atoms from a set of high-resolution protein structures and associated molecular dynamics simulations in water. We included more-recently appreciated, but weaker NCIs in our analysis, such as n->pi* interactions, Calpha-H bonds and methyl-H bonds. The data demonstrate balanced, dynamic systems for all proteins, with most backbone-carbonyl oxygen atoms being satisfied by two NCIs most of the time. Combinations of NCIs made may correlate with secondary structure type, though in subtly different ways from traditional models of alpha- and beta-structure. In addition, we find examples of under- and over-satisfied carbonyl-oxygen atoms, and we identify both sequence-dependent and sequence-independent secondary structural motifs in which these reside. Our analysis provides a more-detailed understanding of these contributors to protein structure and stability, which will be of use in protein modeling, engineering and design. PMID- 26833777 TI - Chronic endothelin-1 infusion causes adipocyte hyperplasia in rats. AB - OBJECTIVE: The aim of this study was to investigate the regulatory mechanism of endothelin-1 (ET-1), an endothelium-derived vasoconstrictor, on adipogenesis in vitro and in vivo. METHODS: 3T3-L1 preadipocytes were used to explore the mechanisms mediating ET-1 actions on preadipocyte proliferation and adipocyte differentiation. To investigate the in vivo effect of ET-1, male Sprague-Dawley rats were infused with ET-1 or saline for 4 weeks via intraperitoneally implanted osmotic pumps, and the fat pad weight and adipocyte size of adipose tissues were measured. RESULTS: ET-1 stimulated preadipocyte proliferation and increased the cell number at the mitotic clonal expansion stage of adipocyte differentiation via the endothelin A receptor (ETAR) and activation of the protein kinase C (PKC) pathway. ET-1, via ETAR, inhibited adipocyte differentiation partially through an ERK-dependent pathway. Furthermore, no significant difference in the body weight and fat pad weight was observed in either ET-1- or saline-infused rats. Compared with saline-infused rats, the adipocyte cell number was significantly increased but the adipocyte size was significantly decreased in ET-1-infused rats. CONCLUSIONS: Chronic ET-1 infusion increased the number of small adipocytes without the change of white adipose tissue mass in rats, which were associated with ET-1-stimulated preadipocyte proliferation, but not ET-1-suppressed adipocyte differentiation. PMID- 26833779 TI - Flowering pathway is regulated by bulb size in Lilium longiflorum (Easter lily). AB - Lilium longiflorum (Easter lily) vegetative propagation occurs through production of underground bulbs containing apical and axillary meristems. In addition, sexual reproduction is achieved by flowering of elongated shoots above the bulb. It is generally accepted that L. longiflorum has an obligatory requirement for vernalisation and that long day (LD) regime hastens flowering. However, the effect of bulb size and origin, with respect to axillary or apical meristems on flowering, as well as the interactions between these meristems are largely unknown. The aim of this study was to explore the effect of bulb size, vernalisation and photoperiod on L. longiflorum flowering. To this end, we applied vernalisation and photoperiod treatments to the different bulb sizes and used a system of constant ambient temperature of 25 degrees C, above vernalisation spectrum, to avoid cold-dependent floral induction during plant growth. Vernalisation and LD hasten flowering in all bulbs. Large, non-vernalised bulbs invariably remained at a vegetative stage. However, small non-vernalised bulbs flowered under LD conditions. These results demonstrate for the first time that cold exposure is not an obligatory prerequisite for L. longiflorum flowering, and that an alternative flowering pathway can bypass vernalisation in small bulbs. We suggest that apical dominance interactions determine the distinct flowering pathways of the apical and axillary meristems. Similar floral induction is achieved in propagated bulblets from scaling. These innovative findings in the field of geophyte floral induction represent valuable applicative knowledge for lily production. PMID- 26833775 TI - Prevention and treatment of cancers by immune modulating nutrients. AB - Epidemiological and laboratory data support the protective effects of bioactive nutrients in our diets for various diseases. Along with various factors, such as genetic history, alcohol, smoking, exercise, and dietary choices play a vital role in affecting an individual's immune responses toward a transforming cell, by either preventing or accelerating a neoplastic transformation. Ample evidence suggests that dietary nutrients control the inflammatory and protumorigenic responses in immune cells. Immunoprevention is usually associated with the modulation of immune responses that help in resolving the inflammation, thus improving clinical outcome. Various metabolic pathway-related nutrients, including glutamine, arginine, vitamins, minerals, and long-chain fatty acids, are important components of immunonutrient mixes. Epidemiological studies related to these substances have reported different results, with no or minimal effects. However, several studies suggest that these nutrients may have immune-modulating effects that may lower cancer risk. Preclinical studies submit that most of these components may provide beneficial effects. The present review discusses the available data, the immune-modulating functions of these nutrients, and how these substances could be used to study immune modulation in a neoplastic environment. Further research will help to determine whether the mechanistic signaling pathways in immune cells altered by nutrients can be exploited for cancer prevention and treatment. PMID- 26833781 TI - Traditional Male Circumcision: Ways to Prevent Deaths Due to Dehydration. AB - Deaths of initiates occurring in the circumcision initiation schools are preventable. Current studies list dehydration as one of the underlying causes of deaths among traditional male circumcision initiates in the Eastern Cape, a province in South Africa, but ways to prevent dehydration in the initiation schools have not been adequately explored. The goals of this study were to (a) explore the underlying determinants of dehydration among initiates aged from 12 to 18 years in the traditional male circumcision initiation schools and (b) determine knowledge of participants on the actions to be taken to prevent dehydration. The study was conducted at Libode, a rural area falling under Nyandeni municipality. A simple random sampling was used to select three focus group discussions with 36 circumcised boys. A purposive sampling was used to select 10 key informants who were matured and experienced people with knowledge of traditional practices and responsible positions in the communities. The research findings indicate that the practice has been neglected to inexperienced, unskillful, and abusive traditional attendants. The overall themes collated included traditional reasons for water restriction, imbalanced food nutrients given to initiates, poor environmental conditions in the initiation hut, and actions that should be taken to prevent dehydration. This article concludes with discussion and recommendation of ways to prevent dehydration of initiates in the form of a comprehensive circumcision health promotion program. PMID- 26833780 TI - Acceleration of bone formation during fracture healing by poly(pro-hyp-gly)10 and basic fibroblast growth factor containing polycystic kidney disease and collagen binding domains from Clostridium histolyticum collagenase. AB - Growth factor delivered in combination with animal-derived collagen materials has been used to accelerate bone fracture healing in human patients. However, the introduction of bovine proteins into humans carries the risk of zoonotic and immunologic complications. Here, we developed a collagen-like polypeptide-based bone formation system consisting of poly(Pro-Hyp-Gly)10 , which mimics the triple helical conformation of collagen, and basic fibroblast growth factor (bFGF) fused to the polycystic kidney disease (PKD) domain and collagen-binding domain (CBD) of Clostridium histolyticum collagenase. Circular dichroism spectral analysis showed that when pepsin-soluble bovine type I collagen was treated at 50 degrees C, a positive signal corresponding to the collagen triple helix at 220 nm was not detected. In contrast, poly(Pro-Hyp-Gly)10 retained the 220-nm positive peak, even when treated at 80 degrees C. The combination of the collagen binding-bFGF fusion protein (bFGF-PKD-CBD) with poly(Pro-Hyp-Gly)10 induced greater bone formation compared to bFGF alone in mice bone fracture models. Taken together, these properties suggest that the bFGF-PKD-CBD/poly(Pro-Hyp-Gly)10 composite is a promising material for bone repair in the clinical setting. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1372-1378, 2016. PMID- 26833782 TI - Diagnosing pulmonic valve infective endocarditis with positron emission tomography-CT. AB - Infective endocarditis (IE) affects the pulmonic valve in less than 2% of cases. Not only is pulmonary valve IE rare, it is also challenging to visualise with commonly used imaging modalities. In this vignette, we present a 50-year-old patient with a history of repaired Tetralogy of Fallot who underwent a prolonged hospitalisation and extensive work up for fever of unknown origin. Although we suspected IE as the source of his fevers, he had persistently negative transthoracic and transoesophageal echocardiograms. We were ultimately able to establish the diagnosis with the use of positron emission tomography-CT (PET-CT). Although PET-CT is not part of the traditional work up for IE, it can be a useful imaging modality when there is a high index of suspicion for IE with negative echocardiography findings. PMID- 26833783 TI - Monolithic 3D CMOS Using Layered Semiconductors. AB - Monolithic 3D integrated circuits using transition metal dichalcogenide materials and low-temperature processing are reported. A variety of digital and analog circuits are implemented on two sequentially integrated layers of devices. Inverter circuit operation at an ultralow supply voltage of 150 mV is achieved, paving the way to high-density, ultralow-voltage, and ultralow-power applications. PMID- 26833784 TI - Needhi Bhalla: Chromosomes do the most amazing things. PMID- 26833785 TI - Dynamics of the actin cytoskeleton mediates receptor cross talk: An emerging concept in tuning receptor signaling. AB - Recent evidence implicates the actin cytoskeleton in the control of receptor signaling. This may be of particular importance in the context of immune receptors, such as the B cell receptor, where dysregulated signaling can result in autoimmunity and malignancy. Here, we discuss the role of the actin cytoskeleton in controlling receptor compartmentalization, dynamics, and clustering as a means to regulate receptor signaling through controlling the interactions with protein partners. We propose that the actin cytoskeleton is a point of integration for receptor cross talk through modulation of protein dynamics and clustering. We discuss the implication of this cross talk via the cytoskeleton for both ligand-induced and low-level constitutive (tonic) signaling necessary for immune cell survival. PMID- 26833786 TI - EHBP1L1 coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells. AB - The highly conserved Rab guanosine triphosphatase (GTPase) Rab8 plays a role in exocytosis toward the polarized plasma membrane in eukaryotic cells. In murine Rab8-deficient small intestine cells, apical proteins are missorted into lysosomes. In this study, we identified a novel Rab8-interacting protein complex containing an EH domain-binding protein 1-like 1 (EHBP1L1), Bin1/amphiphysin II, and dynamin. Biochemical analyses showed that EHBP1L1 directly bound to GTP loaded Rab8 and Bin1. The spatial dependency of these complexes at the endocytic recycling compartment (ERC) was demonstrated through overexpression and knockdown experiments. EHBP1L1- or Bin1-depleted or dynamin-inhibited small intestine organoids significantly accumulated apical membrane proteins but not basolateral membrane proteins in lysosomes. Furthermore, in EHBP1L1-deficient mice, small intestine cells displayed truncated and sparse microvilli, suggesting that EHBP1L1 maintains the apical plasma membrane by regulating apical transport. In summary, our data demonstrate that EHBP1L1 links Rab8 and the Bin1-dynamin complex, which generates membrane curvature and excises the vesicle at the ERC for apical transport. PMID- 26833787 TI - Unattached kinetochores rather than intrakinetochore tension arrest mitosis in taxol-treated cells. AB - Kinetochores attach chromosomes to the spindle microtubules and signal the spindle assembly checkpoint to delay mitotic exit until all chromosomes are attached. Light microscopy approaches aimed to indirectly determine distances between various proteins within the kinetochore (termed Delta) suggest that kinetochores become stretched by spindle forces and compact elastically when the force is suppressed. Low Delta is believed to arrest mitotic progression in taxol treated cells. However, the structural basis of Delta remains unknown. By integrating same-kinetochore light microscopy and electron microscopy, we demonstrate that the value of Delta is affected by the variability in the shape and size of outer kinetochore domains. The outer kinetochore compacts when spindle forces are maximal during metaphase. When the forces are weakened by taxol treatment, the outer kinetochore expands radially and some kinetochores completely lose microtubule attachment, a condition known to arrest mitotic progression. These observations offer an alternative interpretation of intrakinetochore tension and question whether Delta plays a direct role in the control of mitotic progression. PMID- 26833788 TI - Distinct requirements for intra-ER sorting and budding of peroxisomal membrane proteins from the ER. AB - During de novo peroxisome biogenesis, importomer complex proteins sort via two preperoxisomal vesicles (ppVs). However, the sorting mechanisms segregating peroxisomal membrane proteins to the preperoxisomal endoplasmic reticulum (pER) and into ppVs are unknown. We report novel roles for Pex3 and Pex19 in intra endoplasmic reticulum (ER) sorting and budding of the RING-domain peroxins (Pex2, Pex10, and Pex12). Pex19 bridged the interaction at the ER between Pex3 and RING domain proteins, resulting in a ternary complex that was critical for the intra ER sorting and subsequent budding of the RING-domain peroxins. Although the docking subcomplex proteins (Pex13, Pex14, and Pex17) also required Pex19 for budding from the ER, they sorted to the pER independently of Pex3 and Pex19 and were spatially segregated from the RING-domain proteins. We also discovered a unique role for Pex3 in sorting Pex10 and Pex12, but with the docking subcomplex. Our study describes an intra-ER sorting process that regulates segregation, packaging, and budding of peroxisomal importomer subcomplexes, thereby preventing their premature assembly at the ER. PMID- 26833791 TI - Gene signatures in osteoarthritic acetabular labrum using microarray analysis. AB - BACKGROUND: Osteoarthritis (OA) is the most common chronic joint disease. This study aimed to uncover underlying mechanisms of OA pathogenesis and explore the potential biomarkers of osteoarthritic acetabular labrum. METHODS: The microarray data GSE60762 was utilized, containing five OA acetabular labrum samples and three healthy control samples. Data were preprocessed by oligo package and the differentially expressed genes (DEGs) were identified using limma package with predefined criteria, followed by functional enrichment analysis by the GoFunction in R Bioconductor, and protein-protein interaction (PPI) network analysis. RESULTS: As a result, 141 DEGs (44 were up-regulated and 97 were down-regulated) were identified between OA and healthy acetabular labrum cells. Up-regulated genes including CDH2 and WNT5A were significantly enriched in intracellular signal transduction function, while down-regulated genes such as KDR, FLT1 and CDH5 were remarkably correlated with cardiovascular system development. FLT1, KDR, CDH2 and CDH5 were the striking nodes in the PPI network. CONCLUSION: CDH2, WNT5A, KDR, FLT1 and CDH5 might serve as the biomarkers of OA prognosis. Intracellular signal transduction and cardiovascular system development might play significant roles in the destruction of labrum during OA progression. However, more experimental validations are warranted to confirm our findings. PMID- 26833789 TI - Modulation of FAK and Src adhesion signaling occurs independently of adhesion complex composition. AB - Integrin adhesion complexes (IACs) form mechanochemical connections between the extracellular matrix and actin cytoskeleton and mediate phenotypic responses via posttranslational modifications. Here, we investigate the modularity and robustness of the IAC network to pharmacological perturbation of the key IAC signaling components focal adhesion kinase (FAK) and Src. FAK inhibition using AZ13256675 blocked FAK(Y397) phosphorylation but did not alter IAC composition, as reported by mass spectrometry. IAC composition was also insensitive to Src inhibition using AZD0530 alone or in combination with FAK inhibition. In contrast, kinase inhibition substantially reduced phosphorylation within IACs, cell migration and proliferation. Furthermore using fluorescence recovery after photobleaching, we found that FAK inhibition increased the exchange rate of a phosphotyrosine (pY) reporter (dSH2) at IACs. These data demonstrate that kinase dependent signal propagation through IACs is independent of gross changes in IAC composition. Together, these findings demonstrate a general separation between the composition of IACs and their ability to relay pY-dependent signals. PMID- 26833790 TI - Gene regulation and speciation in house mice. AB - One approach to understanding the process of speciation is to characterize the genetic architecture of post-zygotic isolation. As gene regulation requires interactions between loci, negative epistatic interactions between divergent regulatory elements might underlie hybrid incompatibilities and contribute to reproductive isolation. Here, we take advantage of a cross between house mouse subspecies, where hybrid dysfunction is largely unidirectional, to test several key predictions about regulatory divergence and reproductive isolation. Regulatory divergence between Mus musculus musculus and M. m. domesticus was characterized by studying allele-specific expression in fertile hybrid males using mRNA-sequencing of whole testes. We found extensive regulatory divergence between M. m. musculus and M. m. domesticus, largely attributable to cis regulatory changes. When both cis and trans changes occurred, they were observed in opposition much more often than expected under a neutral model, providing strong evidence of widespread compensatory evolution. We also found evidence for lineage-specific positive selection on a subset of genes related to transcriptional regulation. Comparisons of fertile and sterile hybrid males identified a set of genes that were uniquely misexpressed in sterile individuals. Lastly, we discovered a nonrandom association between these genes and genes showing evidence of compensatory evolution, consistent with the idea that regulatory interactions might contribute to Dobzhansky-Muller incompatibilities and be important in speciation. PMID- 26833792 TI - The prevalence of skin tears in the acute care setting in Singapore. AB - Skin tears appear to be a hidden and extensive problem despite an increased focus in the literature on skin tear epidemiology, prevention strategies and management modalities. Currently, there has been no report of skin tear epidemiology published in Singapore. The aim of the present study was to pilot the methodology by WoundWest at one of the tertairy hospitals in Singapore. The secondary objective was to determine the prevalence and current nursing management of skin tears within two selected acute medical wards in the hospital. A point prevalence survey was conducted within the two medical wards. Six registered nurses acted as the surveyors and underwent pre-survey education. Inter-rater reliability testing was conducted. Surveyors were paired and performed skin examinations on all available patients in the two wards. Data were collected on age, gender, skin tear anatomical locations, their Skin Tear Audit Research categories, dressings used on identified skin tears and related documentation. A total of 144 (98%) patients consented to skin inspections. Findings demonstrated a skin tear prevalence of 6.2%; all skin tears were found to be hospital-acquired and located on the extremities. Most (78%) were in the age range of 70-89 years. There was a dearth in nursing documentation of the skin tears identified and their management. The findings suggested that nurses were lacking in the knowledge of skin tears, and documentation, if available, was not consistent. There is an urgent clinical need for the implementation of a validated skin tear classification tool; standardised protocols for skin tear prevention and management; and a comprehensive skin tear educational programme for hospital care staff. Quarterly hospital-wide skin tear prevalence surveys are also needed to evaluate improvement strategies. PMID- 26833793 TI - In Vitro Analysis of Surface Roughness of Acrylic Resin Exposed to the Combined Hygiene Method of Brushing and Immersion in Ricinus communis and Sodium Hypochlorite. AB - PURPOSE: To evaluate a solution based on Ricinus communis (Castor oil) for denture cleansing, comparing it to sodium hypochlorite (NaOCl) for the surface roughness of heat-polymerized acrylic resin. MATERIALS AND METHODS: Forty polished and unpolished resin specimens (90 * 30 * 4 mm) were evaluated before and after their exposure to protocol hygiene: brushing the specimens with a specific denture brush and mild soap for 3 minutes, three times a day, and immersing them in hygiene solutions (0.25% NaOCl-S1 and 0.5% NaOCl-S2; 10% R. communis-S3; saline-S4: control) for 20 minutes. Surface roughness was evaluated by rugosimeter and scanning electron microscopy (SEM) before and after the protocol. For evaluation of surface roughness, polished and unpolished surfaces were used. RESULTS: The roughness of the polished surface was not affected by time (p = 0.062), but was affected by solutions (p < 0.0001) and the interaction between factors (p = 0.005). For S1 and S4, the period did not influence the roughness. For S2, there was a change after 7 days, remaining stable after 14 days. For S3, there were changes, and stabilization occurred after 14 days. After 7 and 14 days, S2 and S3 promoted major changes, but after 21 days, there were no differences among solutions, except saline. The unpolished surface was not influenced by factors: period (p = 0.115), solution (p = 0.120), and their interaction (p = 0.382). SEM analysis showed similar results on the evaluation of surface roughness. CONCLUSIONS: The polished surface of the prosthesis was more susceptible to changes when exposed to hygiene solutions, and although the 0.5% NaOCl solution promoted an increase in the surface roughness compared with the same solution at 0.25% and R. communis at 10%, the values are clinically acceptable. PMID- 26833795 TI - A novel HLA-B*37 allele, HLA-B*37:58, identified in a Turkish family. AB - New allele HLA-B*37:58 differs from HLA-B*37:01:01 by one nucleotide at position 449 in exon 2. PMID- 26833794 TI - Searching for cognitive enhancement in the Morris water maze: better and worse performance in D-amino acid oxidase knockout (Dao(-/-)) mice. AB - A common strategy when searching for cognitive-enhancing drugs has been to target the N-methyl-d-aspartate receptor (NMDAR), given its putative role in synaptic plasticity and learning. Evidence in favour of this approach has come primarily from studies with rodents using behavioural assays like the Morris water maze. D amino acid oxidase (DAO) degrades neutral D-amino acids such as D-serine, the primary endogenous co-agonist acting at the glycine site of the synaptic NMDAR. Inhibiting DAO could therefore provide an effective and viable means of enhancing cognition, particularly in disorders like schizophrenia, in which NMDAR hypofunction is implicated. Indirect support for this notion comes from the enhanced hippocampal long-term potentiation and facilitated water maze acquisition of ddY/Dao(-) mice, which lack DAO activity due to a point mutation in the gene. Here, in Dao knockout (Dao(-/-) ) mice, we report both better and worse water maze performance, depending on the radial distance of the hidden platform from the side wall of the pool. Dao(-/-) mice displayed an increased innate preference for swimming in the periphery of the maze (possibly due to heightened anxiety), which facilitated the discovery of a peripherally located platform, but delayed the discovery of a centrally located platform. By contrast, Dao(-/-) mice exhibited normal performance in two alternative assays of long-term spatial memory: the appetitive and aversive Y-maze reference memory tasks. Taken together, these results question the proposed relationship between DAO inactivation and enhanced long-term associative spatial memory. They also have generic implications for how Morris water maze studies are performed and interpreted. PMID- 26833796 TI - Spatial Stigma and Health in Postindustrial Detroit. AB - An emerging body of research suggests that those who reside in socially and economically marginalized places may be marked by a stigma of place, referred to as spatial stigma, which influences their sense of self, their daily experiences, and their relations with outsiders. Researchers conducted 60 semistructured interviews at partnering community-based organizations during summer 2011 with African American and Latina/o, structurally disadvantaged youth of diverse gender and sexual identities who were between 18 and 26 years of age residing in Detroit, Michigan. The disadvantaged structural conditions and dilapidated built environment were common themes in participants' narratives. Beyond these descriptions, participants' framings and expressions of their experiences in and perceptions of these spaces alluded to reputational qualities of their city and particular areas of their city that appear related to spatial stigma. Young Detroit residents articulated the ways that they experience and navigate the symbolic degradation of their city. PMID- 26833797 TI - Is Multiple System Atrophy a New Prion Disorder? PMID- 26833798 TI - Exact confidence intervals for the average causal effect on a binary outcome. AB - Based on the physical randomization of completely randomized experiments, in a recent article in Statistics in Medicine, Rigdon and Hudgens propose two approaches to obtaining exact confidence intervals for the average causal effect on a binary outcome. They construct the first confidence interval by combining, with the Bonferroni adjustment, the prediction sets for treatment effects among treatment and control groups, and the second one by inverting a series of randomization tests. With sample size n, their second approach requires performing O(n4 )randomization tests. We demonstrate that the physical randomization also justifies other ways to constructing exact confidence intervals that are more computationally efficient. By exploiting recent advances in hypergeometric confidence intervals and the stochastic order information of randomization tests, we propose approaches that either do not need to invoke Monte Carlo or require performing at most O(n2) randomization tests. We provide technical details and R code in the Supporting Information. PMID- 26833799 TI - SIMPRE1.2: Considering the hyperfine and quadrupolar couplings and the nuclear spin bath decoherence. AB - SIMPRE is a fortran77 code which uses an effective electrostatic model of point charges to predict the magnetic behavior of rare-earth-based mononuclear complexes. In this article, we present SIMPRE1.2, which now takes into account two further phenomena. First, SIMPRE now considers the hyperfine and quadrupolar interactions within the rare-earth ion, resulting in a more complete and realistic set of energy levels and wave functions. Second, and to widen SIMPRE's predictive capabilities regarding potential molecular spin qubits, it now includes a routine that calculates an upper-bound estimate of the decoherence time considering only the dipolar coupling between the electron spin and the surrounding nuclear spin bath. Additionally, SIMPRE now allows the user to introduce the crystal field parameters manually. Thus, we are able to demonstrate the new features using as examples (i) a Gd-based mononuclear complex known for its properties both as a single ion magnet and as a coherent qubit and (ii) an Er based mononuclear complex. (c) 2016 Wiley Periodicals, Inc. PMID- 26833800 TI - One Among Many: Anaphoric One and Its Relationship With Numeral One. AB - One anaphora (e.g., this is a good one) has been used as a key diagnostic in syntactic analyses of the English noun phrase, and "one-replacement" has also figured prominently in debates about the learnability of language. However, much of this work has been based on faulty premises, as a few perceptive researchers, including Ray Jackendoff, have made clear. Abandoning the view of anaphoric one (a-one) as a form of syntactic replacement allows us to take a fresh look at various uses of the word one. In the present work, we investigate its use as a cardinal number (1-one) in order to better understand its anaphoric use. Like all cardinal numbers, 1-one can only quantify an individuated entity and provides an indefinite reading by default. Owing to unique combinatoric properties, cardinal numbers defy consistent classification as determiners, quantifiers, adjectives, or nouns. Once the semantics and distribution of cardinal numbers, including 1 one, are appreciated, many properties of a-one follow with minimal stipulation. We claim that 1-one and a-one are distinct but very closely related lexemes. When 1-one appears without a noun (e.g., Take one), it is nearly indistinguishable from a-one (e.g., take one)-the only differences being interpretive (1-one foregrounds its cardinality while a-one does not) and prosodic (presence versus absence of primary accent). While we ultimately argue that a family of constructions is required to describe the full range of syntactic contexts in which one appears, the proposed network accounts for properties of a-one by allowing it to inherit most of its syntactic and interpretive constraints from its historical predecessor, 1-one. PMID- 26833801 TI - Dual Chemical Modification of a Polytheonamide Mimic: Rational Design and Synthesis of Ion-Channel-Forming 48-mer Peptides with Potent Cytotoxicity. AB - Polytheonamide B (1) is a natural peptide that displays potent cytotoxicity against P388 mouse leukemia cells (IC50 =0.098 nm). Linear 48-mer 1 is known to form monovalent cation channels on binding to lipid bilayers. We previously developed a fully synthetic route to 1, and then achieved the design and synthesis of a structurally simplified analogue of 1, namely, dansylated polytheonamide mimic 2. Although the synthetically more accessible 2 was found to emulate the channel function of 1, its cytotoxicity was decreased 120-fold. Herein, the chemical preparation and biological evaluation of seven analogues 3-9 of 2 are reported. Compounds 3-9 were modified at their N terminus and/or the side chain of residue 44 of 2 to alter their physicochemical properties. The total synthesis of 3-9 was accomplished in a unified fashion by a combination of solid-phase and solution-phase chemistry. Systematic evaluation of the hydrophobicities, single-channel currents, ion-exchange activities, and cytotoxicities of 3-9 revealed that their hydrophobicities are correlated with the total magnitude of ion exchange and determine their cytotoxic potency. Consequently, the most hydrophobic analogue 9 exhibited the lowest IC50 value, which is comparable to that of 1. Therefore, these results clarified that the bioactivity of the polytheonamide-based peptides can be rationally controlled by changing their hydrophobicity at the N and C termini of the 48-amino-acid sequence. PMID- 26833802 TI - Caribbean Urological Association 17th Annual Conference. PMID- 26833804 TI - Single-staged vs. two-staged implant placement using bone ring technique in vertically deficient alveolar ridges - Part 1: histomorphometric and micro-CT analysis. AB - BACKGROUND: Simultaneous implant placement with bone grafting shortens the overall treatment period, but might lead to the peri-implant bone loss or even implant failure. The aim of this study was to compare the single-staged to two staged implant placement using the bone ring technique. MATERIAL AND METHODS: Four standardized alveolar bone defects were made in the mandibles of nine dogs. Dental implants (Straumann BL(r) , Basel, Switzerland) were inserted simultaneously with bone ring technique in test group and after 6 months of healing period in control group. Animals of both groups were euthanized at 3 and 6 months of osseointegration period. The harvested samples were analyzed by means of histology and micro-CT. RESULTS: The amount of residual bone decreased while the amount of new bone increased up to 9 months of healing period. All morphometric parameters remained stable between 3 and 6 months of osseointegration period within groups. Per a given time point, median area of residual bone graft was higher in test group and area of new bone in control group. The volume of bone ring was greater in test than in control group, reaching the significance at 6 months of osseointegration period (P = 0.002). CONCLUSIONS: In the present type of bone defect, single-staged implant placement may be potentially useful to shorten an overall treatment period. PMID- 26833805 TI - Effects of longitudinal body mass index variability on microvasculature over 5 years in adult Chinese. AB - OBJECTIVE: To explore the associations of 5-year trend and fluctuation in body mass index (BMI) with retinal vascular caliber in a middle-aged and elderly Chinese population. METHODS: Participants age >=40 years were recruited in a prospective study. Baseline BMI data were collected in 2008, and the participants were re-examined annually until 2012. Retinal vascular caliber was measured from fundus photographs collected in 2012. BMI trend was calculated as the slope of BMI against the time of examinations. BMI fluctuation was defined as the root mean square error around the regression line of BMI over time (BMI RMSE) and the coefficient of variation of BMI (BMI CV). RESULTS: Rising BMI trend was associated with narrower retinal arteriolar and wider venular calibers in the overall subjects, especially among persons with overweight and obesity (BMI >= 25 kg/m(2) , P = 0.004 and 0.033, respectively). Rising BMI trend was also significantly associated with narrower retinal arteriole even in nonobese individuals with BMI < 25 kg/m(2) (P = 0.017) when eliminating the effects of hypertension and diabetes. Neither BMI RMSE nor BMI CV was statistically associated with retinal vascular caliber (all P > 0.05). CONCLUSIONS: Annual rising trending BMI was associated with retinal microvascular alteration. The results suggest that weight gain probably increases the risk of cardiovascular diseases among middle-aged and elderly people. PMID- 26833807 TI - Advanced interatrial block in hemodialysis patients. PMID- 26833806 TI - Epistasis in protein evolution. AB - The structure, function, and evolution of proteins depend on physical and genetic interactions among amino acids. Recent studies have used new strategies to explore the prevalence, biochemical mechanisms, and evolutionary implications of these interactions-called epistasis-within proteins. Here we describe an emerging picture of pervasive epistasis in which the physical and biological effects of mutations change over the course of evolution in a lineage-specific fashion. Epistasis can restrict the trajectories available to an evolving protein or open new paths to sequences and functions that would otherwise have been inaccessible. We describe two broad classes of epistatic interactions, which arise from different physical mechanisms and have different effects on evolutionary processes. Specific epistasis-in which one mutation influences the phenotypic effect of few other mutations-is caused by direct and indirect physical interactions between mutations, which nonadditively change the protein's physical properties, such as conformation, stability, or affinity for ligands. In contrast, nonspecific epistasis describes mutations that modify the effect of many others; these typically behave additively with respect to the physical properties of a protein but exhibit epistasis because of a nonlinear relationship between the physical properties and their biological effects, such as function or fitness. Both types of interaction are rampant, but specific epistasis has stronger effects on the rate and outcomes of evolution, because it imposes stricter constraints and modulates evolutionary potential more dramatically; it therefore makes evolution more contingent on low-probability historical events and leaves stronger marks on the sequences, structures, and functions of protein families. PMID- 26833808 TI - Kinetics of Reactive Modules Adds Discriminative Dimensions for Selective Cell Imaging. AB - Living cells are chemical mixtures of exceptional interest and significance, whose investigation requires the development of powerful analytical tools fulfilling the demanding constraints resulting from their singular features. In particular, multiplexed observation of a large number of molecular targets with high spatiotemporal resolution appears highly desirable. One attractive road to address this analytical challenge relies on engaging the targets in reactions and exploiting the rich kinetic signature of the resulting reactive module, which originates from its topology and its rate constants. This review explores the various facets of this promising strategy. We first emphasize the singularity of the content of a living cell as a chemical mixture and suggest that its multiplexed observation is significant and timely. Then, we show that exploiting the kinetics of analytical processes is relevant to selectively detect a given analyte: upon perturbing the system, the kinetic window associated to response read-out has to be matched with that of the targeted reactive module. Eventually, we introduce the state-of-the-art of cell imaging exploiting protocols based on reaction kinetics and draw some promising perspectives. PMID- 26833803 TI - Medications development for the treatment of alcohol use disorder: insights into the predictive value of animal and human laboratory models. AB - Development of effective treatments for alcohol use disorder (AUD) represents an important public health goal. This review provides a summary of completed preclinical and clinical studies testing pharmacotherapies for the treatment of AUD. We discuss opportunities for improving the translation from preclinical findings to clinical trial outcomes, focusing on the validity and predictive value of animal and human laboratory models of AUD. Specifically, while preclinical studies of medications development have offered important insights into the neurobiology of the disorder and alcohol's molecular targets, limitations include the lack of standardized methods and streamlined processes whereby animal studies can readily inform human studies. Behavioral pharmacology studies provide a less expensive and valuable opportunity to assess the feasibility of a pharmacotherapy prior to initiating larger scale clinical trials by providing insights into the mechanism of the drug, which can then inform recruitment, analyses, and assessments. Summary tables are provided to illustrate the wide range of preclinical, human laboratory, and clinical studies of medications development for alcoholism. Taken together, this review highlights the challenges associated with animal paradigms, human laboratory studies, and clinical trials with the overarching goal of advancing treatment development and highlighting opportunities to bridge the gap between preclinical and clinical research. PMID- 26833810 TI - Gynecological involvement in eosinophilic granulomatosis with polyangiitis. AB - Gynceological involvement in antineutrophil cytoplasmic antibody (ANCA) associated vasculitides is rare. We describe a case of ANCA-associated vasculitis in an elderly woman presenting with fevers, cough and a rash. Further investigations revealed vasculitic involvement of the ovaries, fallopian tubes, uterus and omentum with an eosinophil-rich infiltrate. PMID- 26833809 TI - Distinct physiological, plasma amino acid, and liver transcriptome responses to purified dietary beef, chicken, fish, and pork proteins in young rats. AB - SCOPE: We report on the impact of purified dietary meat proteins from four species on plasma insulin, lipid and amino acid (AA) concentrations, and hepatic transcriptome (RNA-sequencing). METHODS AND RESULTS: Young rats received semi synthetic diets for 1 wk that differed only regarding protein source; casein (reference) was replaced by beef, chicken, fish, or pork proteins. Compared to casein, all proteins, except pork, increased total plasma AA concentrations. Pork protein reduced adipose tissue mass and liver triacylglycerol, which was accompanied by increased plasma triacylglycerol concentrations. Plasma cholesterol was reduced by fish protein. The number of differentially expressed genes ranged between 609 (pork) and 1258 (chicken); on average one-third of the changes were specific for each meat protein. Pathway responses were most similar for beef and chicken, followed by pork and fish. Although the extent varied, all meat proteins induced mRNA translation, antigen processing/presentation, intracellular vesicular trafficking, and oxidoreductive-transformation pathways, and suppressed signal-transduction (Notch, TGFB/SMAD, insulin) and mitochondrial biogenesis pathways. Lipid- and AA-metabolic pathways were repressed, except by pork. AA-transport pathways were induced by beef and fish only, and complement/coagulation-pathways were suppressed by chicken and beef. Fish suppressed nuclear-transport and cofactor metabolism. CONCLUSION: To conclude, short-term feeding of different meat proteins resulted in distinct physiological and transcriptome changes in young rats. PMID- 26833811 TI - Influence of collagen concentration and glutaraldehyde on collagen-based scaffold properties. AB - Several studies have shown the influence of the physical properties of scaffolds on their mechanical properties. An initial characterization of a type of collagen protein was carried out by studying its composition andits solubility at different pH values and infrared spectroscopy. Subsequently, porosity and scaffold pore size were studied, assessing how varying the composition of the initial solution (increasing the protein concentration or adding glutaraldehyde) changed the properties of the final scaffolds obtained. Lastly, rheological measurements were performed to evaluate the mechanical strength of the scaffolds. The initial characterization revealed that the type I collagen protein used is considerably denatured. In addition, increasing the protein content in the scaffold decreases the porosity, related to an increase in the elastic modulus producing an enhancement of its mechanical strength, while adding glutaraldehyde to the scaffold increases its mechanical strength without lowering its pore size or porosity. The results obtained are useful in that they demonstrate that it is possible to design a scaffold with specific properties, by just controlling the collagen concentration or adding glutaraldehyde to the initial solution. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1462-1468, 2016. PMID- 26833812 TI - Effects of Graphene Quantum Dots on the Self-Renewal and Differentiation of Mesenchymal Stem Cells. AB - The influence of graphene quantum dots (GQDs) on key characteristics of bone marrow derived mesenchymal stem cells (MSCs) phenotype (i.e., self-renewal, differentiation potential, and pluripotency) is systematically investigated in this work. First, the viability and impact of GQDs on the self-renewal potential of MSCs is evaluated in order to determine a threshold for the exposing dose. Second, GQDs uptake by MSCs is confirmed due to the excellent fluorescent properties of the particles. They exhibit a homogenous cytoplasmatic distribution that increases with the time and concentration. Third, the impact of GQDs on the osteogenic differentiation of MSCs is deeply characterized. An enhanced activity of alkaline phosphatase promoted by GQDs indicates early activation of osteogenesis. This is also confirmed upon GQD-induced up-regulation of phenotypically related osteogenic genes (Runx2, osteopontin, and osteocalcin) and specific biomarkers expression (osteopontin and osteocalcin). GQDs also effectively enhance the formation of calcium-rich deposits characteristics of osteoblasts. Furthermore, genes microarray results indicate that the enhanced osteogenic differentiation of MSCs by GQDs is in progress through a bone morphogenetic protein and transforming growth factor-beta relative signaling pathways. Finally, intracytoplasmatic lipid detection shows that GQDs can also promote the adipogenic differentiation of MSCs, thus confirming the prevalence of their pluripotency potential. PMID- 26833813 TI - MoS2 -Based Tactile Sensor for Electronic Skin Applications. AB - A conformal tactile sensor based on MoS2 and graphene is demonstrated. The MoS2 tactile sensor exhibits excellent sensitivity, high uniformity, and good repeatability in terms of various strains. In addition, the outstanding flexibility enables the MoS2 strain tactile sensor to be realized conformally on a finger tip. The MoS2 -based tactile sensor can be utilized for wearable electronics, such as electronic skin. PMID- 26833814 TI - Neurochemical and behavioural indices of exercise reward are independent of exercise controllability. AB - Brain reward circuits are implicated in stress-related psychiatric disorders. Exercise reduces the incidence of stress-related disorders, but the contribution of exercise reward to stress resistance is unknown. Exercise-induced stress resistance is independent of exercise controllability; both voluntary running (VR) and forced running (FR) protect rats against the anxiety-like and depression like behavioural consequences of stress. Voluntary exercise is a natural reward, but whether rats find FR rewarding is unknown. Moreover, the contribution of dopamine (DA) and striatal reward circuits to exercise reward is not well characterized. Adult, male rats were assigned to locked wheels, VR, or FR groups. FR rats were forced to run in a pattern resembling the natural wheel running behavior of rats. Both VR and FR increased the reward-related plasticity marker DeltaFosB in the dorsal striatum and nucleus accumbens, and increased the activity of DA neurons in the lateral ventral tegmental area, as revealed by immunohistochemistry for tyrosine hydroxylase and pCREB. Both VR and FR rats developed conditioned place preference (CPP) to the side of a CPP chamber paired with exercise. Re-exposure to the exercise-paired side of the CPP chamber elicited conditioned increases in cfos mRNA in direct-pathway (dynorphin positive) neurons in the dorsal striatum and nucleus accumbens in both VR and FR rats, and in tyrosine hydroxylase-positive neurons in the lateral ventral tegmental area of VR rats only. The results suggest that the rewarding effects of exercise are independent of exercise controllability and provide insight into the DA and striatal circuitries involved in exercise reward and exercise-induced stress resistance. PMID- 26833815 TI - An In Vitro Study of Condylar Displacement Caused by Interocclusal Records: Influence of Recording Material, Storage Time, and Recording Technique. AB - PURPOSE: To evaluate the condylar displacement after mounting working casts using different interocclusal recording materials and to analyze the influence of the storage time and the recording technique on the displacement caused by the interocclusal record. MATERIALS AND METHODS: Eight interocclusal records were made in each of the following groups: G1: Aluwax (aluminum wax), G2: Beauty Pink wax (hydrocarbon wax compound), G3: Futar D Fast, G4: Futar Scan (G3, G4: vinylpolysiloxane), G5: Ramitec (polyether), G6: LuxaBite (composite resin based on bis-acryl), G7: LuxaBite corrected with Aluwax. A condylar-positioning indicator measured the condylar displacement in the three planes after storage of the records for two periods of 1 and 48 hours. Two-way ANOVA was used to determine the influences of recording materials and each of the following factors: (1) region (record and non-record side), (2) storage time, and (3) recording technique. The statistical significance level was set at p < 0.05. RESULTS: The vertical displacement caused by the interocclusal records in the record side after storage time of 1 hour ranged between 0.29 mm (Aluwax) and 0.14 mm (Futar Scan). The lateral displacement ranged between 0.13 mm (Aluwax) and 0.02 mm (Ramitec) while the anteroposterior displacement ranged between 0.15 mm (Ramitec) and 0.04 mm (Futar Scan). The corrected resin record showed generally lower displacement values than other materials tested (0.03, 0.02, and 0.07, respectively). On the non-record side, the values were lower than that on the record side. The condylar displacement increased after a storage time of 48 hours for all materials. Both factors, storage time and recording technique, had statistically significant influence on the condylar displacement. CONCLUSIONS: Based on the results, the vertical displacement of the condyle caused by the interocclusal records was higher than the lateral or the anteroposterior displacement. Elastomers caused statistically significantly less condylar displacement than waxes or uncorrected composite resin. Corrected LuxaBite records with Aluwax showed significantly less condylar displacement than all other materials. PMID- 26833816 TI - Sequence-based prediction of protein-peptide binding sites using support vector machine. AB - Protein-peptide interactions are essential for all cellular processes including DNA repair, replication, gene-expression, and metabolism. As most protein-peptide interactions are uncharacterized, it is cost effective to investigate them computationally as the first step. All existing approaches for predicting protein peptide binding sites, however, are based on protein structures despite the fact that the structures for most proteins are not yet solved. This article proposes the first machine-learning method called SPRINT to make Sequence-based prediction of Protein-peptide Residue-level Interactions. SPRINT yields a robust and consistent performance for 10-fold cross validations and independent test. The most important feature is evolution-generated sequence profiles. For the test set (1056 binding and non-binding residues), it yields a Matthews' Correlation Coefficient of 0.326 with a sensitivity of 64% and a specificity of 68%. This sequence-based technique shows comparable or more accurate than structure-based methods for peptide-binding site prediction. SPRINT is available as an online server at: http://sparks-lab.org/. (c) 2016 Wiley Periodicals, Inc. PMID- 26833818 TI - Hip joint pathology: relationship between patient history, physical tests, and arthroscopy findings in clinical practice. AB - The purpose of this retrospective cohort study was to (a) describe the clinical presentation of femoroacetabular impingement (FAI) and hip labral pathology; (b) describe the accuracy of patient history and physical tests for FAI and labral pathology as confirmed by hip arthroscopy. Patients (18-65 years) were included if they were referred to a physical therapist to gather pre-operative data and were then diagnosed during arthroscopy. Results of pre-operative patient history and physical tests were collected and compared to arthroscopy. Data of 77 active patients (mean age: 37 years) were included. Groin as main location of pain, the Anterior Impingement test (AIT), Flexion-Abduction-External Rotation (FABER) test, and Fitzgerald test had a high sensitivity (range 0.72-0.91). Sensitivity increased when combining these tests (0.97) as either groin as main location of pain and a positive FABER test or a positive AIT and a positive FABER test were the shortest most sensitive combinations. The results of this study point out that in clinical practice absence of groin as main location of pain combined with a negative FABER test or the combination of a negative AIT and a negative FABER test are suggested to rule out the diagnosis of symptomatic FAI and/or labral pathology. PMID- 26833819 TI - Rituximab protects podocytes and exerts anti-proteinuric effects in rat adriamycin-induced nephropathy independent of B-lymphocytes. AB - AIM: This study was aimed at examining the effects of treatment with rituximab, a chimeric monoclonal antibody against the protein CD20, in a B-lymphocyte independent adriamycin-induced rat model of nephrotic syndrome. Rituximab is an emerging rescue therapy used in patients with complicated nephrotic syndrome and, therefore, we sought to elucidate the apparent B-lymphocyte independent mechanism underlying its anti-proteinuric effect. METHODS: Adriamycin-induced nephropathy was established in Wistar rats by intravenously injecting 10 mg/kg of adriamycin, which were then treated with rituximab or purified human IgG weekly and euthanized on day 28. Proteinuria, glomerular expression of sphingomyelin phosphodiesterase acid-like 3b protein, and podocyte-related proteins were examined using immunofluorescence staining and a reverse transcription-polymerase chain reaction. RESULTS: Rituximab treatment of rats with adriamycin-induced nephropathy significantly reduced urinary protein excretion 14 to 28 days after induction of disease, compared with those treated with purified normal human IgG. Furthermore, rituximab treatment also prevented the reduction of glomerular nephrin and podocin expression on day 28. Double-immunofluorescence staining revealed that after in vivo administration, rituximab was bound to the glomeruli, which also expressed synaptopodin or sphingomyelin phosphodiesterase, acid-like 3b. Moreover, sphingomyelin phosphodiesterase, acid-like 3b expression was significantly decreased on day 28 of adriamycin-induced nephropathy, which was also prevented by rituximab. CONCLUSIONS: This study demonstrated that rituximab directly affected glomerular podocytes and ameliorated proteinuria in adriamycin induced nephropathy in rats. Furthermore, protection of podocyte function by rituximab may be mediated by direct modulation of a sphingomyelin phosphodiesterase, acid-like 3b-dependent mechanism. PMID- 26833820 TI - European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators significantly outperform the Prostate Cancer Prevention Trial (PCPT) 2.0 in the prediction of prostate cancer: a multi-institutional study. AB - OBJECTIVE: To analyse the performance of the Prostate Cancer Prevention Trial Risk Calculator (PCPT-RC) and two iterations of the European Randomised Study of Screening for Prostate Cancer (ERSPC) Risk Calculator, one of which incorporates prostate volume (ERSPC-RC) and the other of which incorporates prostate volume and the prostate health index (PHI) in a referral population (ERSPC-PHI). PATIENTS AND METHODS: The risk of prostate cancer (PCa) and significant PCa (Gleason score >=7) in 2001 patients from six tertiary referral centres was calculated according to the PCPT-RC and ERSPC-RC formulae. The calculators' predictions were analysed using the area under the receiver-operating characteristic curve (AUC), calibration plots, Hosmer-Lemeshow test for goodness of fit and decision-curve analysis. In a subset of 222 patients for whom the PHI score was available, each patient's risk was calculated as per the ERSPC-RC and ERSPC-PHI risk calculators. RESULTS: The ERSPC-RC outperformed the PCPT-RC in the prediction of PCa, with an AUC of 0.71 compared with 0.64, and also outperformed the PCPT-RC in the prediction of significant PCa (P<0.001), with an AUC of 0.74 compared with 0.69. The ERSPC-RC was found to have improved calibration in this cohort and was associated with a greater net benefit on decision-curve analysis for both PCa and significant PCa. The performance of the ERSPC-RC was further improved through the addition of the PHI score in a subset of 222 patients. The AUCs of the ERSPC-PHI were 0.76 and 0.78 for PCa and significant PCa prediction, respectively, in comparison with AUC values of 0.72 in the prediction of both PCa and significant PCa for the ERSPC-RC (P = 0.12 and P = 0.04, respectively). The ERSPC-PHI risk calculator was well calibrated in this cohort and had an increase in net benefit over that of the ERSPC-RC. CONCLUSIONS: The performance of the risk calculators in the present cohort shows that the ERSPC-RC is a superior tool in the prediction of PCa; however the performance of the ERSPC-RC in this population does not yet warrant its use in clinical practice. The incorporation of the PHI score into the ERSPC-PHI risk calculator allowed each patient's risk to be more accurately quantified. Individual patient risk calculation using the ERSPC-PHI risk calculator can be undertaken in order to allow a systematic approach to patient risk stratification and to aid in the diagnosis of PCa. PMID- 26833822 TI - Planar Chiral Phosphoramidites with a Paracyclophane Scaffold: Synthesis, Gold(I) Complexes, and Enantioselective Cycloisomerization of Dienynes. AB - The key structural feature of the new phosphoramidites is a paracyclophane scaffold in which two aryl rings are tethered by both a 1,8-biphenylene unit and a O-P-O bridge. Suitable aryl substituents generate planar chirality. The corresponding gold(I) complexes promote the cycloisomerization of prochiral nitrogen-tethered dienynes. These reactions afford bicyclo[4.1.0]heptene derivatives displaying three contiguous stereogenic centers, with very high diastereoselectivity and up to 95 % ee. PMID- 26833821 TI - Characterization of white matter integrity deficits in cocaine-dependent individuals with substance-induced psychosis compared with non-psychotic cocaine users. AB - With sufficient drug exposure, some individuals develop transient psychotic symptoms referred to as 'substance-induced psychosis' (SIP), which closely resemble the symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and the schizophrenias suggests that similar underlying neural deficits may contribute to the emergence of psychosis across these disorders. Only a small number of studies have investigated structural alterations in SIP, and all have been limited to volumetric imaging methods, with none controlling for the effects of chronic drug exposure. To investigate white matter abnormalities associated with SIP, diffusion tensor imaging was employed in a group of individuals with cocaine associated psychosis (CAP; n = 24) and a cocaine-dependent non-psychotic (CDN) group (n = 43). Tract-based spatial statistics was used to investigate group differences in white matter diffusion parameters. The CAP group showed significantly lower fractional anisotropy values than the CDN group (p < 0.05) in voxels within white matter tracts of fronto-temporal, fronto-thalamic and interhemispheric pathways. The greatest differences in white matter integrity were present in the corpus callosum, corona radiata, bilateral superior longitudinal fasciculi and bilateral inferior longitudinal fasciculi. Additionally, the CAP group had voxels of significantly higher radial diffusivity in a subset of the previously mentioned pathways. These results are the first description of white matter integrity abnormalities in a SIP sample and indicate that differences in these pathways may be a shared factor in the expression of different forms of psychosis. PMID- 26833823 TI - Physical activity attenuates genetic effects on BMI: Results from a study of Chinese adult twins. AB - OBJECTIVE: This study aimed to examine the gene-environment interaction of physical activity and body mass index (BMI) using the Chinese National Twin Registry (CNTR). METHODS: A total of 19,308 same-sex adult twins from CNTR were included in the analysis. Twin zygosity was determined by self-reported questionnaire. Height and weight were measured using self-reported questionnaire. The vigorous physical activity was defined as greater or equal to five times a week of at least 30 min moderate- or high-intensity physical activity. A twin structural equation model was used to analyze the gene-environment interaction of vigorous exercise with BMI among 13,506 monozygotic twins and 5,802 dizygotic twins. RESULTS: A structural equation model adjusting for age and sex found vigorous exercise significantly moderated the additive genetic effects (P < 0.001) and shared environmental effects (P < 0.001) on BMI. The genetic contributions to BMI were significantly lower for people who adopted a physically active lifestyle [h(2) = 40%, 95% confidence interval (CI): 35%-46%] than those who were relative sedentary (h(2) = 59%, 95% CI: 52%-66%). The observed gene physical activity interaction was more pronounced in men than women. CONCLUSIONS: Our results suggested that adopting a physically active lifestyle may help to reduce the genetic influence on BMI among the Chinese population. PMID- 26833824 TI - Direct care nurses on the shared governance journey towards positive patient outcomes. AB - AIMS AND OBJECTIVES: To describe shared governance in action through the example of one paediatric institution's decision to institute daily chlorhexidine bathing. BACKGROUND: Shared governance processes are discussed extensively in the literature; however, implementation of the processes can be challenging. Recently nurses at one paediatric hospital were involved in a hospital-wide practice change where the theoretical approach of shared governance was actualised. Several questions arose from direct care nurses about unwarranted variations in bathing practices across settings and whether bathing standardisation could address the recent increase in central line-associated bloodstream infections. Shared governance council members identified daily chlorhexidine bathing as a potential intervention to standardise bathing across the hospital and to decrease infection rates. At this time, chlorhexidine bathing had been widely adopted in adult hospitals but was less commonly practiced in paediatric institutions. DESIGN: This is a position paper describing the use of shared governance to make a house-wide practice decision and positively impact patient outcomes. METHOD: Inquiry Council members conducted a systematic evidence search on best practices around chlorhexidine bathing. This evidence was used in Practice Council discussions to standardise house-wide practice. Once consensus was achieved, council members collaborated with Education Council to ensure understanding, competency, and the adoption and sustainment of the practice change. CONCLUSIONS: Patients with central lines are at decreased risk for acquiring a central line associated blood stream infection due, in part, to the change in nursing practice to include daily chlorhexidine bathing. The shared governance structure was the vehicle through which this practice was vetted and instituted. RELEVANCE TO CLINICAL PRACTICE: This paper provides a real-life example of leveraging shared governance structures and the direct care nurse leaders within the councils when an organisation faces critical needs in patient care. PMID- 26833825 TI - Attitudes toward stress and coping among primary caregivers of patients undergoing hemodialysis: A Q-methodology study. AB - Introduction Hemodialysis (HD) causes many life changes, not only for patients undergoing it but also for their families by allowing them to rely on this lifesaving equipment unless they receive a kidney transplant. The stress of the primary caregivers, who spends the most time in the family taking care of the patient undergoing HD, is quite high. This study was to identify attitudes about stress and coping among primary caregivers of HD patients. Methods Q-methodology was undertaken because it integrates quantitative and qualitative research methods. A convenience sample of 33 primary caregivers of HD patients participated. Forty selected Q-samples were obtained from each participant and were classified into a forced normal distribution using a nine-point grid. Data was analyzed using a pc-QUANL program. Findings Three discrete factors emerged as follows: Factor I (they reduced their stress by participating in religious activities; religious sublimation), Factor II (they always worried about the caregiving situations and about the patients' conditions; nervousness), and Factor III (they thought it better to accept their stressful situations; leading handler). Three factors accounted for 44.5% of all the variance, including Factor I (26.0%), Factor II (10.1%), and Factor III (8.4%). The eigenvalues were 8.58, 3.34, and 2.79, respectively. Discussion The subjectivities of the three factors that were identified can be applied during the planning stages of effective interventions for stress and coping. Healthcare workers in clinical practices should consider assesses primary caregivers' attitudes about stress and coping and approaches their situation to cope with it and to adapt to lifestyle changes. PMID- 26833826 TI - Excited-State Deactivation of Adenine by Electron-Driven Proton-Transfer Reactions in Adenine-Water Clusters: A Computational Study. AB - The reactivity of photoexcited 9H-adenine with hydrogen-bonded water molecules in the 9H-adenine-(H2 O)5 cluster is investigated by using ab initio electronic structure methods, focusing on the photoreactivity of the three basic sites of 9H adenine. The energy profiles of excited-state reaction paths for electron/proton transfer from water to adenine are computed. For two of the three sites, a barrierless or nearly barrierless reaction path towards a low-lying S1 -S0 conical intersection is found. This reaction mechanism, which is specific for adenine in an aqueous environment, can explain the substantially shortened excited-state lifetime of 9H-adenine in water. Depending on the branching ratio of the nonadiabatic dynamics at the S1 -S0 conical intersection, the electron/proton transfer process can enhance the photostability of 9H-adenine in water or can lead to the generation of adenine-H(?) and OH(?) free radicals. Although the branching ratio is yet unknown, these findings indicate that adenine might have served as a catalyst for energy harvesting by water splitting in the early stages of the evolution of life. PMID- 26833827 TI - Polyampholyte- and nanosilicate-based soft bionanocomposites with tailorable mechanical and cell adhesion properties. AB - Engineered tissues are excellent substitutes for treating organ failure associated with disease, injury, and degeneration. Designing new biomaterials with controlled release profiles, good mechanical properties, and cell adhesion characteristics can be useful for the formation of specific functional tissues. Here, we report the formulation of nanocomposite hydrogels based on carboxylated poly-l-lysine and synthetic clay laponite XLG in which four-arm polyethylene glycol with N-hydroxy succinimide ester (PEG-NHS) was used as the chemical crosslinker. Interestingly, the degradation of this gel could be adjusted from a few days to a few months. Incorporation of laponite XLG resulted in the formation of mechanically tough hydrogels and conferred cytocompatibility. The mechanical properties of the nanocomposite could be modulated by changing the crosslinking density and laponite concentration. The feasibility of using this system for cellular therapies was investigated by evaluating cell adhesion on the nanocomposite surface. Thus, these nanocomposites can serve as scaffolds with tunable mechanical and degradation properties that also provide structural integrity to tissue constructs. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1379-1386, 2016. PMID- 26833828 TI - Particles for Local Delivery of Proteins Using Intra-Articular Route. AB - Designing a vehicle for local delivery of proteins using intra-articular route is an attractive option to minimize the adverse effects associated with systemic exposure and to maximize the efficacy. Slowly dissolving silylated microparticles are designed with specific size and shape that are capable of extending the retention time of a model protein (bovine serum albumin) in the murine knee joint. No cytotoxicity is observed for the reconstituted formulation when tested against synovial fibroblasts and RAW 264.7 macrophages. PMID- 26833829 TI - Multifaceted origins of sex differences in the brain. AB - Studies of sex differences in the brain range from reductionistic cell and molecular analyses in animal models to functional imaging in awake human subjects, with many other levels in between. Interpretations and conclusions about the importance of particular differences often vary with differing levels of analyses and can lead to discord and dissent. In the past two decades, the range of neurobiological, psychological and psychiatric endpoints found to differ between males and females has expanded beyond reproduction into every aspect of the healthy and diseased brain, and thereby demands our attention. A greater understanding of all aspects of neural functioning will only be achieved by incorporating sex as a biological variable. The goal of this review is to highlight the current state of the art of the discipline of sex differences research with an emphasis on the brain and to contextualize the articles appearing in the accompanying special issue. PMID- 26833830 TI - Genetic dissection of neural circuits underlying sexually dimorphic social behaviours. AB - The unique hormonal, genetic and epigenetic environments of males and females during development and adulthood shape the neural circuitry of the brain. These differences in neural circuitry result in sex-typical displays of social behaviours such as mating and aggression. Like other neural circuits, those underlying sex-typical social behaviours weave through complex brain regions that control a variety of diverse behaviours. For this reason, the functional dissection of neural circuits underlying sex-typical social behaviours has proved to be difficult. However, molecularly discrete neuronal subpopulations can be identified in the heterogeneous brain regions that control sex-typical social behaviours. In addition, the actions of oestrogens and androgens produce sex differences in gene expression within these brain regions, thereby highlighting the neuronal subpopulations most likely to control sexually dimorphic social behaviours. These conditions permit the implementation of innovative genetic approaches that, in mammals, are most highly advanced in the laboratory mouse. Such approaches have greatly advanced our understanding of the functional significance of sexually dimorphic neural circuits in the brain. In this review, we discuss the neural circuitry of sex-typical social behaviours in mice while highlighting the genetic technical innovations that have advanced the field. PMID- 26833832 TI - Establishing a link between sex-related differences in the structural connectome and behaviour. AB - Recent years have witnessed an increased attention to studies of sex differences, partly because such differences offer important considerations for personalized medicine. While the presence of sex differences in human behaviour is well documented, our knowledge of their anatomical foundations in the brain is still relatively limited. As a natural gateway to fathom the human mind and behaviour, studies concentrating on the human brain network constitute an important segment of the research effort to investigate sex differences. Using a large sample of healthy young individuals, each assessed with diffusion MRI and a computerized neurocognitive battery, we conducted a comprehensive set of experiments examining sex-related differences in the meso-scale structures of the human connectome and elucidated how these differences may relate to sex differences at the level of behaviour. Our results suggest that behavioural sex differences, which indicate complementarity of males and females, are accompanied by related differences in brain structure across development. When using subnetworks that are defined over functional and behavioural domains, we observed increased structural connectivity related to the motor, sensory and executive function subnetworks in males. In females, subnetworks associated with social motivation, attention and memory tasks had higher connectivity. Males showed higher modularity compared to females, with females having higher inter-modular connectivity. Applying multivariate analysis, we showed an increasing separation between males and females in the course of development, not only in behavioural patterns but also in brain structure. We also showed that these behavioural and structural patterns correlate with each other, establishing a reliable link between brain and behaviour. PMID- 26833833 TI - Genetic regulation of sex differences in songbirds and lizards. AB - Sex differences in the morphology of neural and peripheral structures related to reproduction often parallel the frequency of particular behaviours displayed by males and females. In a variety of model organisms, these sex differences are organized in development by gonadal steroids, which also act in adulthood to modulate behavioural expression and in some cases to generate parallel anatomical changes on a seasonal basis. Data collected from diverse species, however, suggest that changes in hormone availability are not sufficient to explain sex and seasonal differences in structure and function. This paper pulls together some of this literature from songbirds and lizards and considers the information in the broader context of taking a comparative approach to investigating genetic mechanisms associated with behavioural neuroendocrinology. PMID- 26833831 TI - Sex differences in sleep: impact of biological sex and sex steroids. AB - Men and women sleep differently. While much is known about the mechanisms that drive sleep, the reason for these sex differences in sleep behaviour is unknown and understudied. Historically, women and female animals are underrepresented in studies of sleep and its disorders. Nevertheless, there is a growing recognition of sex disparities in sleep and rhythm disorders. Women typically report poorer quality and more disrupted sleep across various stages of life. Findings from clinical and basic research studies strongly implicate a role for sex steroids in sleep modulation. Understanding how neuroendocrine mediators and sex differences influence sleep is central to advancing our understanding of sleep-related disorders. The investigation into sex differences and sex steroid modulation of sleep is in its infancy. Identifying the mechanisms underlying sex and gender differences in sleep will provide valuable insights leading to tailored therapeutics that benefit each sex. The goal of this review is to discuss our current understanding of how biological sex and sex steroids influence sleep behaviour from both the clinical and pre-clinical perspective. PMID- 26833835 TI - Epigenetic mechanisms in sexual differentiation of the brain and behaviour. AB - Circumstantial evidence alone argues that the establishment and maintenance of sex differences in the brain depend on epigenetic modifications of chromatin structure. More direct evidence has recently been obtained from two types of studies: those manipulating a particular epigenetic mechanism, and those examining the genome-wide distribution of specific epigenetic marks. The manipulation of histone acetylation or DNA methylation disrupts the development of several neural sex differences in rodents. Taken together, however, the evidence suggests there is unlikely to be a simple formula for masculine or feminine development of the brain and behaviour; instead, underlying epigenetic mechanisms may vary by brain region or even by dependent variable within a region. Whole-genome studies related to sex differences in the brain have only very recently been reported, but suggest that males and females may use different combinations of epigenetic modifications to control gene expression, even in cases where gene expression does not differ between the sexes. Finally, recent findings are discussed that are likely to direct future studies on the role of epigenetic mechanisms in sexual differentiation of the brain and behaviour. PMID- 26833834 TI - The importance of having two X chromosomes. AB - Historically, it was thought that the number of X chromosomes plays little role in causing sex differences in traits. Recently, selected mouse models have been used increasingly to compare mice with the same type of gonad but with one versus two copies of the X chromosome. Study of these models demonstrates that mice with one X chromosome can be strikingly different from those with two X chromosomes, when the differences are not attributable to confounding group differences in gonadal hormones. The number of X chromosomes affects adiposity and metabolic disease, cardiovascular ischaemia/reperfusion injury and behaviour. The effects of X chromosome number are likely the result of inherent differences in expression of X genes that escape inactivation, and are therefore expressed from both X chromosomes in XX mice, resulting in a higher level of expression when two X chromosomes are present. The effects of X chromosome number contribute to sex differences in disease phenotypes, and may explain some features of X chromosome aneuploidies such as in Turner and Klinefelter syndromes. PMID- 26833836 TI - Hypothalamic control of the male neonatal testosterone surge. AB - Sex differences in brain neuroanatomy and neurophysiology underpin considerable physiological and behavioural differences between females and males. Sexual differentiation of the brain is regulated by testosterone secreted by the testes predominantly during embryogenesis in humans and the neonatal period in rodents. Despite huge advances in understanding how testosterone, and its metabolite oestradiol, sexually differentiate the brain, little is known about the mechanism that actually generates the male-specific neonatal testosterone surge. This review examines the evidence for the role of the hypothalamus, and particularly the gonadotropin-releasing hormone (GnRH) neurons, in generating the neonatal testosterone surge in rodents and primates. Kisspeptin-GPR54 signalling is well established as a potent and critical regulator of GnRH neuron activity during puberty and adulthood, and we argue here for an equally important role at birth in driving the male-specific neonatal testosterone surge in rodents. The presence of a male-specific population of preoptic area kisspeptin neurons that appear transiently in the perinatal period provide one possible source of kisspeptin drive to neonatal GnRH neurons in the mouse. PMID- 26833837 TI - Species variation in the degree of sex differences in brain and behaviour related to birdsong: adaptations and constraints. AB - The song-control system, a neural circuit that controls the learning and production of birdsong, provided the first example in vertebrates of prominent macro-morphological sex differences in the brain. Forebrain nuclei HVC, robust nucleus of the arcopallium (RA) and area X all exhibit prominent male-biased sex differences in volume in zebra finches and canaries. Subsequent studies compared species that exhibited different degrees of a sex difference in song behaviour and revealed an overall positive correlation between male biases in song behaviour and male biases in the volume of the song nuclei. However, several exceptions have been described in which male biases in HVC and RA are observed even though song behaviour is equal or even female-biased. Other phenotypic measures exhibit lability in both sexes. In the duetting plain-tailed wren (Pheugopedius euophrys), males and females have auditory cells in the song system that are tuned to the joint song the two sexes produce rather than just male or female components. These findings suggest that there may be constraints on the adaptive response of the song system to ecological conditions as assessed by nucleus volume but that other critical variables regulating song can respond so that each sex can modify its song behaviour as needed. PMID- 26833838 TI - Sex differences in partner preferences in humans and animals. AB - A large number of morphological, physiological and behavioural traits are differentially expressed by males and females in all vertebrates including humans. These sex differences, sometimes, reflect the different hormonal environment of the adults, but they often remain present after subjects of both sexes are placed in the same endocrine conditions following gonadectomy associated or not with hormonal replacement therapy. They are then the result of combined influences of organizational actions of sex steroids acting early during development, or genetic differences between the sexes, or epigenetic mechanisms differentially affecting males and females. Sexual partner preference is a sexually differentiated behavioural trait that is clearly controlled in animals by the same type of mechanisms. This is also probably true in humans, even if critical experiments that would be needed to obtain scientific proof of this assertion are often impossible for pragmatic or ethical reasons. Clinical, epidemiological and correlative studies provide, however, converging evidence strongly suggesting, if not demonstrating, that endocrine, genetic and epigenetic mechanisms acting during the pre- or perinatal life control human sexual orientation, i.e. homosexuality versus heterosexuality. Whether they interact with postnatal psychosexual influences remains, however, unclear at present. PMID- 26833839 TI - Perils and pitfalls of reporting sex differences. AB - The idea of sex differences in the brain both fascinates and inflames the public. As a result, the communication and public discussion of new findings is particularly vulnerable to logical leaps and pseudoscience. A new US National Institutes of Health policy to consider both sexes in almost all preclinical research will increase the number of reported sex differences and thus the risk that research in this important area will be misinterpreted and misrepresented. In this article, I consider ways in which we might reduce that risk, for example, by (i) employing statistical tests that reveal the extent to which sex explains variation, rather than whether or not the sexes 'differ', (ii) properly characterizing the frequency distributions of scores or dependent measures, which nearly always overlap, and (iii) avoiding speculative functional or evolutionary explanations for sex-based variation, which usually invoke logical fallacies and perpetuate sex stereotypes. Ultimately, the factor of sex should be viewed as an imperfect, temporary proxy for yet-unknown factors, such as hormones or sex linked genes, that explain variation better than sex. As scientists, we should be interested in discovering and understanding the true sources of variation, which will be more informative in the development of clinical treatments. PMID- 26833841 TI - An examination of sex differences in the effects of early-life opiate and alcohol exposure. AB - Early-life exposure to drugs and alcohol is one of the most preventable causes of developmental, behavioural and learning disorders in children. Thus a significant amount of basic, animal and human research has focused on understanding the behavioural consequences and the associated neural effects of exposure to drugs and alcohol during early brain development. Despite this, much of the previous research that has been done on this topic has used predominantly male subjects or rodents. While many of the findings from these male-specific studies may ultimately apply to females, the purpose of this review is to highlight the research that has also examined sex as a factor and found striking differences between the sexes in their response to early-life opiate and alcohol exposure. Finally, we will also provide a framework for scientists interested in examining sex as a factor in future experiments that specifically examine the consequences of early-life drug and alcohol exposure. PMID- 26833842 TI - A trip down memory lane about sex differences in the brain. AB - Scientific studies funded by the United States government must now include both males and females as experimental subjects. This is a welcomed change for those of us who have been reporting on sex differences for decades. That said, there are some issues to consider; I focus on one in this review: females used in animal models of mental illness and health are almost always virgins and yet most adult females around the world, irrespective of species, are not virgins. I am not advocating that all scientists include non-virgin females in laboratory studies, but rather to consider the dynamic nature of the female brain when drawing conclusions through discovery. Stressful life experiences, including those related to sexual aggression and trauma, can have a lasting impact on processes of learning related to mental health and plasticity in the female brain. Her response to stress can change rather dramatically as she emerges from puberty to become pregnant and produce offspring, as she must learn to care for those offspring. The inclusion of females in scientific research has been a long time coming but it comes with a history. Going forward, we should take advantage of that history to generate hypotheses that are both reasonable and meaningful. PMID- 26833840 TI - Sex differences in the gut microbiome-brain axis across the lifespan. AB - In recent years, the bidirectional communication between the gut microbiome and the brain has emerged as a factor that influences immunity, metabolism, neurodevelopment and behaviour. Cross-talk between the gut and brain begins early in life immediately following the transition from a sterile in utero environment to one that is exposed to a changing and complex microbial milieu over a lifetime. Once established, communication between the gut and brain integrates information from the autonomic and enteric nervous systems, neuroendocrine and neuroimmune signals, and peripheral immune and metabolic signals. Importantly, the composition and functional potential of the gut microbiome undergoes many transitions that parallel dynamic periods of brain development and maturation for which distinct sex differences have been identified. Here, we discuss the sexually dimorphic development, maturation and maintenance of the gut microbiome brain axis, and the sex differences therein important in disease risk and resilience throughout the lifespan. PMID- 26833845 TI - Correction to 'The role of self-other distinction in understanding others' mental and emotional states: neurocognitive mechanisms in children and adults'. PMID- 26833843 TI - Prenatal androgen exposure alters girls' responses to information indicating gender-appropriate behaviour. AB - Individual variability in human gender-related behaviour is influenced by many factors, including androgen exposure prenatally, as well as self-socialization and socialization by others postnatally. Many studies have looked at these types of influences in isolation, but little is known about how they work together. Here, we report that girls exposed to high concentrations of androgens prenatally, because they have the genetic condition congenital adrenal hyperplasia, show changes in processes related to self-socialization of gender related behaviour. Specifically, they are less responsive than other girls to information that particular objects are for girls and they show reduced imitation of female models choosing particular objects. These findings suggest that prenatal androgen exposure may influence subsequent gender-related behaviours, including object (toy) choices, in part by changing processes involved in the self-socialization of gendered behaviour, rather than only by inducing permanent changes in the brain during early development. In addition, the findings suggest that some of the behavioural effects of prenatal androgen exposure might be subject to alteration by postnatal socialization processes. The findings also suggest a previously unknown influence of early androgen exposure on later processes involved in self-socialization of gender-related behaviour, and thus expand understanding of the developmental systems regulating human gender development. PMID- 26833844 TI - Beyond sex differences: new approaches for thinking about variation in brain structure and function. AB - In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being. PMID- 26833846 TI - Beyond the Halogen Bond: Examining the Limits of Extended Polybromide Networks through Quantum-Chemical Investigations. AB - The bonding environments of some polybromide monoanions and networks were examined by quantum-chemical methods to investigate electronic interactions between dibromine-dibromine contacts. Examination of thermodynamic parameters and a bond critical point analysis give strong evidence for such bonding modes, which have been previously treated disparately in the literature. The thermodynamic stability of large polybromides up to [Br37 ](-) was also predicted by these methods. PMID- 26833847 TI - A change in social activity affect cognitive function in middle-aged and older Koreans: analysis of a Korean longitudinal study on aging (2006-2012). AB - OBJECTIVE: To examine the association between a changes in social activity and cognitive function in Koreans aged 45 years or older. METHODS: Data were obtained from 6076 participants aged 45 years and older included in the Korean Longitudinal Study of Aging (2006-2012). Cognitive function was measured using the mini-mental state examination-Korean version (MMSE-K). Participation in social activities was classified as "consistent participation," "consistent non participation," "participation to non-participation," and "non-participation to participation." Linear mixed models were used to investigate the relationship between type of social activity (religious organizations, friendship organizations, leisure/culture/sports clubs, family or school reunion, volunteering work, and political organizations), and cognitive function. RESULTS: Individuals who reported "no participation to participation" (b = 0.778, p < 0.0001) and "consistent participation" (b = 0.968, p < 0.0001) were more likely to show reduced cognitive decline than those who reported "consistent non participation" (p < 0.0001 for trend). The positive association between cognitive function and consistent participation in religious activities, friendship organizations, and family/school reunions was particularly strong (b = 0.325, p < 0.0001; b = 0.570, p < 0.0001; b = 0.234, p = 0.0004; respectively, versus consistent non-participation). CONCLUSIONS: Promotion of participation in religious organizations, friendship organizations, and family/school reunions (only for older persons) may help preserve cognitive function in individuals aged 45 years or older in Korea. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833849 TI - Problematising the problem: a critical interpretive review of the literature pertaining to older people with cognitive impairment who fall while hospitalised. AB - This article presents a reflexive account by way of a critical interpretive review of the literature pertaining to falls of older people with cognitive impairment who have been hospitalised in an acute care setting. A key aim of this review was to use thematic analysis and problematisation to challenge assumptions underpinning the current falls literature and to bring into consideration alternate foci of research and new approaches to falls research. An innovative approach is used to generate descriptive and interpretive summaries of the literature which are presented graphically to reveal the prevailing themes and assumptions within. It is argued that currently, falls research in the context of cognitive impairment is constrained by scientism. Meta-paradigmatic approaches, which have the potential to provide a better understanding of why falls may or may not occur among this particular subgroup of older people, are proposed as an alternative. PMID- 26833848 TI - Accuracy of QT interval measurement on electrocardiographs displayed on electronic 'smart' devices. AB - OBJECTIVE: The objective of the study was to compare QT intervals measured on the original bedside electrocardiographs (ECG), facsimile, iPhone, iPad and 17 inch computer monitor. METHODS: This was a prospective, observational study conducted within a tertiary referral metropolitan ED. Thirteen doctors measured the QT intervals of 15 non-identifiable, routinely recorded ECGs using randomly allocated modalities over five sessions. The QT intervals of lead I, II, V2, V4, V6 and one other were measured. Variations between modalities and between doctors were examined (chi(2) and Kruskal-Wallis tests). RESULTS: QT intervals measured on the iPad were significantly lower than the other modalities (P = 0.02). For each lead, there were no differences in QT interval measurement between the modalities (P > 0.05). However, there were significant differences between the QT interval measurements of the participating doctors (range of median QT intervals 480-530 msec, P < 0.001). There were also significant differences between the QT intervals measurement of the leads examined (range of median QT intervals 480-520 msec, P < 0.001). Lead V2 was the most consistent lead (smallest interquartile range), and lead I was the least (QT interval consistently under-estimated). CONCLUSION: The QT interval can be reliably measured using facsimile, iPhone and computer, but not the iPad. However, it varies between doctors. Lead V2 is recommended for QT interval measurement if only a single lead is to be used for clinical purposes. PMID- 26833850 TI - Traumatic brain injury and obesity induce persistent central insulin resistance. AB - Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI. PMID- 26833851 TI - Assessing the consistency of the treatment effect under the discrete random effects model in multiregional clinical trials. AB - In recent years, developing pharmaceutical products via multiregional clinical trials (MRCTs) has become standard. Traditionally, an MRCT would assume that a treatment effect is uniform across regions. However, heterogeneity among regions may have impact upon the evaluation of a medicine's effect. In this study, we consider a random effects model using discrete distribution (DREM) to account for heterogeneous treatment effects across regions for the design and evaluation of MRCTs. We derive an power function for a treatment that is beneficial under DREM and illustrate determination of the overall sample size in an MRCT. We use the concept of consistency based on Method 2 of the Japanese Ministry of Health, Labour, and Welfare's guidance to evaluate the probability for treatment benefit and consistency under DREM. We further derive an optimal sample size allocation over regions to maximize the power for consistency. Moreover, we provide three algorithms for deriving sample size at the desired level of power for benefit and consistency. In practice, regional treatment effects are unknown. Thus, we provide some guidelines on the design of MRCTs with consistency when the regional treatment effect are assumed to fall into a specified interval. Numerical examples are given to illustrate applications of the proposed approach. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833852 TI - Establishment and use of new MDCK II cells overexpressing both UGT1A1 and MRP2 to characterize flavonoid metabolism via the glucuronidation pathway. AB - SCOPE: The purpose of this study is to characterize how overexpression of an efflux transporter and an UDP-glucuronosyltransferase (UGT) affects the cellular kinetics of glucuronidation processes. METHODS AND RESULTS: A new MDCK II cell line overexpressing both MRP2 and UGT1A1 (MDCKII-UGT1A1/MRP2 cells) was developed and used to determine how overexpression of an efflux transporter affects the kinetics of cellular flavonoid glucuronide production. The results showed that most model flavonoids (from a total of 13) were mainly metabolized into glucuronides in the MDCKII-UGT1A1/MRP2 cells and the glucuronides were rapidly excreted. Flavonoids with three or fewer hydroxyl group at 7, 3' or 6 hydroxyl group were also metabolized into sulfates. Mechanistic studies using 7 hydroxylflavone showed that its glucuronide was mainly (90%) effluxed by BCRP with a small (10%) but significant contribution from MRP2. Maximal velocity of glucuronide production MDCK-MRP2/UGT1A1 cells showed a fairly good correlation (R(2) >0.8) with those derived using UGT1A1 microsomes, but other kinetic parameters (e.g., Km ) did not correlate. CONCLUSION: Overexpression of a second efficient efflux transporter did not significantly change the fact that BCRP is the dominant transporter for flavonoid glucuronide nor did it diminish the influence of the efflux transporter as the "gate keeper" of glucuronidation process. PMID- 26833853 TI - Effects of Nordic walking training on functional parameters in Parkinson's disease: a randomized controlled clinical trial. AB - We compare the effects of Nordic walking training (NW) and Free walk (FW) on functional parameters (motor symptoms, balance) and functional mobility (Timed Up and Go at Self-selected Speed - TUGSS, and at forced speed, TUGFS; Self-selected Walking Speed, SSW; locomotor rehabilitation index, LRI) of Parkinson's disease (PD) patients. The study included 33 patients with clinical diagnosis of idiopathic PD, and staging between 1 and 4 in the Hoehn and Yahr scale (H&Y) randomized into two groups: NW (N = 16) and FW (N = 17) for 6 weeks. Baseline characteristics were compared trough a one-way ANOVA. Outcomes were analyzed using the Generalized Estimation Equations (GEE) with a Bonferroni post-hoc. Data were analyzed using SPSS v.20.0. Improvements in UPDRS III (P < 0.001), balance scores (P < 0.035), TUGSS distance (P < 0.001), TUGFS distance (P < 0.001), SSW (P < 0.001), and LRI (P < 0.001) were found for both groups. However, the NW group showed significant differences (P < 0.001) when compared to the FW group for the functional mobility. We conclude the NW improves functional parameters and walking mobility demonstrating that NW is as effective as the FW, including benefits for FW on the functional mobility of people with PD. PMID- 26833855 TI - Periodically Diameter-Modulated Semiconductor Nanowires for Enhanced Optical Absorption. AB - A diameter-modulated silicon nanowire array to enhance the optical absorption across broad spectral range is presented. Periodic shape engineering is achieved using conventional semiconductor processes and the unique optical properties are analyzed. The periodicity in the diameter of the silicon nanowires enables stronger and more closely spaced optical resonances, leading to broadband absorption enhancement. PMID- 26833856 TI - Cleaning Methods for Zirconia Following Salivary Contamination. AB - PURPOSE: To determine the best method of cleaning saliva-contaminated zirconia in preparation for resin bonding. MATERIAL AND METHODS: Flat blocks of zirconia were particle abraded with aluminum oxide and divided into eight groups (n = 10). Groups 1 to 4 were first treated with one coat of an MDP primer (Z-prime Plus) and groups 5 to 8 were left untreated. A thin coat of fresh whole saliva was painted on all specimens (except the control, group 1) and left in contact for 3 minutes. The specimens were then cleaned by rinsing with water for 20 seconds (groups 2 and 5), or cleaned with 35% phosphoric acid for 20 seconds and rinsed (groups 3 and 6), or cleaned with a zirconia cleaning solution (Ivoclean) for 20 seconds and rinsed (groups 4 and 7), or abraded with aluminum oxide particles and rinsed (group 5). Following the cleaning procedure, groups 5 to 8 were treated with one coat of Z-prime Plus. A 2.5 mm diameter tube was filled with composite (Z100), affixed to the zirconia surface, and light-cured. Specimens were stored in water (37 degrees C for 24 hours) followed by thermocycling (5 degrees C to 55 degrees C for 10,000 cycles). Shear bond strength testing was performed at a crosshead speed of 1 mm/min. Bond strength values were compared to the control using a Dunnett's test (alpha = 0.05). Contact angles of the zirconia specimens with and without Z-prime Plus were measured with water using a goniometer. RESULTS: Groups 2, 5, and 8 were not significantly different from the control. Application of Z-prime made the zirconia surface more hydrophobic. CONCLUSIONS: If salivary contamination occurs after MDP application, rinsing off the saliva with water will preserve bond strength. If salivary contamination occurs prior to MDP application, particle abrasion or cleaning with Ivoclean will preserve bond strength. PMID- 26833857 TI - Facile Synthesis, Characterization, and Catalytic Behavior of a Large-Pore Zeolite with the IWV Framework. AB - Large-pore microporous materials are of great interest to process bulky hydrocarbon and biomass-derived molecules. ITQ-27 (IWV) has a two-dimensional pore system bounded by 12-membered rings (MRs) that lead to internal cross sections containing 14 MRs. Investigations into the catalytic behavior of aluminosilicate (zeolite) materials with this framework structure have been limited until now due to barriers in synthesis. The facile synthesis of aluminosilicate IWV in both hydroxide and fluoride media is reported herein using simple, diquaternary organic structure-directing agents (OSDAs) that are based on tetramethylimidazole. In hydroxide media, a zeolite product with Si/Al=14.8-23.2 is obtained, while in fluoride media an aluminosilicate product with Si/Al up to 82 is synthesized. The material produced in hydroxide media is tested for the hydroisomerization of n-hexane, and results from this test reaction suggest that the effective pore size of zeolites with the IWV framework structure is similar to but slightly larger than that of ZSM-12 (MTW), in fairly good agreement with crystallographic data. PMID- 26833858 TI - Becoming pure: identifying generational classes of admixed individuals within lesser and greater scaup populations. AB - Estimating the frequency of hybridization is important to understand its evolutionary consequences and its effects on conservation efforts. In this study, we examined the extent of hybridization in two sister species of ducks that hybridize. We used mitochondrial control region sequences and 3589 double-digest restriction-associated DNA sequences (ddRADseq) to identify admixture between wild lesser scaup (Aythya affinis) and greater scaup (A. marila). Among 111 individuals, we found one introgressed mitochondrial DNA haplotype in lesser scaup and four in greater scaup. Likewise, based on the site-frequency spectrum from autosomal DNA, gene flow was asymmetrical, with higher rates from lesser into greater scaup. However, using ddRADseq nuclear DNA, all individuals were assigned to their respective species with >0.95 posterior assignment probability. To examine the power for detecting admixture, we simulated a breeding experiment in which empirical data were used to create F1 hybrids and nine generations (F2 F10) of backcrossing. F1 hybrids and F2, F3 and most F4 backcrosses were clearly distinguishable from pure individuals, but evidence of admixed histories was effectively lost after the fourth generation. Thus, we conclude that low interspecific assignment probabilities (0.011-0.043) for two lesser and nineteen greater scaup were consistent with admixed histories beyond the F3 generation. These results indicate that the propensity of these species to hybridize in the wild is low and largely asymmetric. When applied to species-specific cases, our approach offers powerful utility for examining concerns of hybridization in conservation efforts, especially for determining the generational time until admixed histories are effectively lost through backcrossing. PMID- 26833859 TI - Wholly Synthetic Molecular Machines. AB - The past quarter of a century has witnessed an increasing engagement on the part of physicists and chemists in the design and synthesis of molecular machines de novo. This minireview traces the development of artificial molecular machines from their prototypes in the form of shuttles and switches to their emergence as motors and pumps where supplies of energy in the form of chemical fuel, electrochemical potential and light activation become a minimum requirement for them to function away from equilibrium. The challenge facing this rapidly growing community of scientists and engineers today is one of putting wholly synthetic molecules to work, both individually and as collections. Here, we highlight some of the recent conceptual and practical advances relating to the operation of wholly synthetic rotary and linear motors. PMID- 26833860 TI - Obesity-driven alterations in adipose-derived stem cells are partially restored by weight loss. AB - OBJECTIVE: The therapeutic potential of adipose-derived stem cells (ASCs) is reduced by various stress-inducing conditions that affect tissue homeostasis such as diabetes, aging, and obesity. Previous works have provided evidence of negative effects of obesity on ASC populations, but it is unclear whether this persists after a weight loss. This study evaluated whether weight loss can restore the attenuated properties found in ASCs derived from populations with obesity (oASCs). METHODS: In vitro functional analyses were performed to investigate the possible recovery properties in mouse oASCs. Using ASCs isolated from subcutaneous tissue from formerly obese mice (dASCs) and control mice (cASCs), cell proliferation, viability, and some regenerative properties in these cells were analyzed compared with oASCs to evaluate the functional cell state. RESULTS: Cell proliferation, viability, and some regenerative properties are strengthened in dASCs and cASCs compared with oASCs. Nevertheless, metabolic analysis reveals a mitochondrial load misbalance and function leading to impaired respiration in dASCs. CONCLUSIONS: This study demonstrates that an initial obese environment triggers a detrimental state in ASCs that is not completely recovered after weight loss. PMID- 26833854 TI - Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis. AB - Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products. PMID- 26833861 TI - Emerging Supramolecular Therapeutic Carriers Based on Host-Guest Interactions. AB - Recent advances in host-guest chemistry have significantly influenced the construction of supramolecular soft biomaterials. The highly selective and non covalent interactions provide vast possibilities of manipulating supramolecular self-assemblies at the molecular level, allowing a rational design to control the sizes and morphologies of the resultant objects as carrier vehicles in a delivery system. In this Focus Review, the most recent developments of supramolecular self assemblies through host-guest inclusion, including nanoparticles, micelles, vesicles, hydrogels, and various stimuli-responsive morphology transition materials are presented. These sophisticated materials with diverse functions, oriented towards therapeutic agent delivery, are further summarized into several active domains in the areas of drug delivery, gene delivery, co-delivery and site specific targeting deliveries. Finally, the possible strategies for future design of multifunctional delivery carriers by combining host-guest chemistry with biological interface science are proposed. PMID- 26833862 TI - Positive effects of low level laser therapy (LLLT) on Bouchard's and Heberden's osteoarthritis. AB - BACKGROUND AND OBJECTIVE: Osteoarthritis (OA) is a common chronic disorder. While research usually focuses on OA of the large joints, OA of the hand receives relatively little attention resulting in a lack of a therapeutic gold standard. Low level laser therapy (LLLT)/photobiomodulation therapy has been successfully used to treat a variety of medical conditions. Nevertheless, its merits in the treatment of (hand) OA remain controversial. The aim of the present study was to examine the longitudinal effect of LLLT on the three major hand OA symptoms-pain, swelling, reduced joint mobility-in patients suffering from Bouchard's and Heberden's OA. STUDY DESIGN/MATERIALS AND METHODS: Thirty-four patients (32 females) aged 61.21 +/- 2.13 years were administered 5-10 LLLT sessions to 85 joints (47 proximal and 38 distal interphalangeal joints). Therapy took place twice a week. Pain (Visual Analogue Scale), ring size (perimeter in mm), and range of motion (extension/flexion) were measured at baseline and after five treatments for all patients, and additionally after seven sessions and 8 weeks after treatment ended for patients who received more than five and seven treatments, respectively. Eighteen patients (37 joints) received only five treatments, 10 patients (29 joints) were administered seven treatments, and six patients (19 joints) were administered 10 LLLT sessions. RESULTS: LLLT significantly reduced pain and ring size and increased range of motion after five and seven treatments (all P's < 0.001). The effects were very large (all eta(2) 's > 0.14). No further significant change occurred between 7 and 10 treatments. The effects achieved after seven sessions persisted for 8 weeks. CONCLUSIONS: LLLT is a safe, non-invasive, efficient and efficacious means to reduce pain and swelling and to increase joint mobility in patients suffering from Heberden's and Bourchard's OA. Further randomized controlled studies are needed to examine medium- to long-term effects as well as the ideal LLLT parameters. Lasers Surg. Med. 48:498-504, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26833863 TI - Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. AB - Sulforaphane (SFN), one of the isothiocyanates, is a biologically active compound extracted from cruciferous vegetables, and has been shown to induce cytotoxic effects on many human cancer cells including human leukemia cells. However, the exact molecular mechanism and altered gene expression associated with apoptosis is unclear. In this study, we investigated SFN-induced cytotoxic effects and whether or not they went through cell-cycle arrest and induction of apoptosis and further examined molecular mechanism and altered gene expression in human leukemia HL-60 cells. Cell viability, cell-cycle distribution, sub-G1 (apoptosis), reactive oxygen species (ROS) and Ca2+ production, levels of mitochondrial membrane potential (DeltaPsim ), and caspase-3, -8, and -9 activities were assayed by flow cytometry. Apoptosis-associated proteins levels and gene expressions were examined by Western blotting and cDNA microarray assays, respectively. Results indicated that SFN decreased viable cells, induced G2/M phase arrest and apoptosis based on sub-G1 phase development. Furthermore, SFN increased ROS and Ca2+ production and decreased the levels of DeltaPsim and activated caspase-3, -8, and -9 activities in HL-60 cells. SFN significantly upregulated the expression of BAX, Bid, Fas, Fas-L, caspase-8, Endo G, AIF, and cytochrome c, and inhibited the antiapoptotic proteins such as Bcl-x and XIAP, that is associated with apoptosis. We also used cDNA microarray to confirm several gene expressions such as caspase -8, -3, -4, -6, and -7 that are affected by SFN. Those results indicated that SFN induced apoptosis in HL-60 cells via Fas and mitochondria-dependent pathways. (c) 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 311-328, 2017. PMID- 26833864 TI - Transcranial Doppler versus transthoracic echocardiography for the detection of patent foramen ovale in patients with cryptogenic cerebral ischemia: A systematic review and diagnostic test accuracy meta-analysis. AB - OBJECTIVE: Patent foramen ovale (PFO) can be detected in up to 43% of patients with cryptogenic cerebral ischemia undergoing investigation with transesophageal echocardiography (TEE). The diagnostic value of transthoracic echocardiography (TTE) in the detection of PFO in patients with cryptogenic ischemic stroke or transient ischemic attack has not been compared with that of transcranial Doppler (TCD) using a comprehensive meta-analytical approach. METHODS: We performed a systematic literature review to identify all prospective observational studies of patients with cryptogenic cerebral ischemia that provided both sensitivity and specificity measures of TTE, TCD, or both compared to the gold standard of TEE. RESULTS: Our literature search identified 35 eligible studies including 3,067 patients. The pooled sensitivity and specificity for TCD was 96.1% (95% confidence interval [CI] = 93.0-97.8%) and 92.4% (95% CI = 85.5-96.1%), whereas the respective measures for TTE were 45.1% (95% CI = 30.8-60.3%) and 99.6% (95% CI = 96.5-99.9%). TTE was superior in terms of higher positive likelihood ratio values (LR+ = 106.61, 95% CI = 15.09-753.30 for TTE vs LR+ = 12.62, 95% CI = 6.52 24.43 for TCD; p = 0.043), whereas TCD demonstrated lower negative likelihood values (LR- = 0.04, 95% CI = 0.02-0.08) compared to TTE (LR- = 0.55, 95% CI = 0.42-0.72; p < 0.001). Finally, the area under the summary receiver operating curve (AUC) was significantly greater (p < 0.001) in TCD (AUC = 0.98, 95% CI = 0.97-0.99) compared to TTE studies (AUC = 0.86, 95% CI = 0.82-0.89). INTERPRETATION: TCD is more sensitive but less specific compared to TTE for the detection of PFO in patients with cryptogenic cerebral ischemia. The overall diagnostic yield of TCD appears to outweigh that of TTE. PMID- 26833866 TI - The mental health and mortality impact of death of a partner with dementia. AB - OBJECTIVE: Caring for a partner with dementia and partner bereavement are independently associated with poor health. An understanding of the health effects of living with a partner dying with dementia can help optimise support. We describe health in the year before and after loss of a partner with dementia compared with other bereavements. METHODS: In a UK primary care database, 2624 older individuals whose partner died with dementia during 2005-2012 were matched with 7512 individuals experiencing bereavement where the deceased partner had no dementia recorded. RESULTS: Prior to bereavement, partners of the deceased with dementia were more likely to be diagnosed with depression (OR 2.31, 1.69-3.14) and receive psychotropic medication (OR 1.34, 1.21-1.49) than partners from bereavements without dementia. In contrast, psychotropic medication initiation two months after dementia bereavement was lower (HR 0.69, 0.56-0.85). Compared with other bereaved individuals, mortality after bereavement was lower in men experiencing a dementia bereavement (HR 0.68, 0.49-0.94) but similar in women (HR 1.02, 0.75-1.38). Prior to bereavement, those who died with dementia were less likely to receive palliative care (OR 0.47, 0.41-0.54). CONCLUSION: In the year before bereavement, partners of individuals dying with dementia experience poorer mental health than those facing bereavement from other causes, and their partner is less likely to receive palliative care. In the year after, individuals whose partner died with dementia experience some attenuation of the adverse health effects of bereavement. Services need to address the needs of carers for individuals dying with dementia and improve access to palliative care. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833867 TI - Neuroprotective Effect of Ginsenoside Rd in Spinal Cord Injury Rats. AB - In this study, the neuroprotective effects of ginsenoside Rd (GS Rd) were evaluated in a rat model of spinal cord injury (SCI). Rats in SCI groups received a T8 laminectomy and a spinal contusion injury. GS Rd 12.5, 25 and 50 mg/kg were administered intraperitoneally 1 hr before the surgery and once daily for 14 days. Dexamethasone 1 mg/kg was administered as a positive control. Locomotor function was evaluated using the BBB score system. H&E staining and Nissl staining were performed to observe the histological changes in the spinal cord. The levels of MDA and GSH and the activity of SOD were assessed to reflect the oxidative stress state. The production of TNF-alpha, IL-1beta and IL-1 was assessed using ELISA kits to examine the inflammatory responses in the spinal cord. TUNEL staining was used to detect the cell apoptosis in the spinal cord. Western blot analysis was used to examine the expression of apoptosis-associated proteins and MAPK proteins. The results demonstrated that GS Rd 25 and 50 mg/kg significantly improved the locomotor function of rats after SCI, reduced tissue injury and increased neuron survival in the spinal cord. Mechanically, GS Rd decreased MDA level, increased GSH level and SOD activity, reduced the production of pro-inflammatory cytokines and prevented cell apoptosis. The effects were equivalent to those of dexamethasone. In addition, GS Rd effectively inhibited the activation of MAPK signalling pathway induced by SCI, which might be involved in the protective effects of GS Rd against SCI. In conclusion, GS Rd attenuates SCI-induced secondary injury through reversing the redox-state imbalance, inhibiting the inflammatory response and apoptosis in the spinal cord tissue. PMID- 26833865 TI - Adult rat cortical thickness changes across age and following adolescent intermittent ethanol treatment. AB - Human studies have established that adolescence is a period of brain maturation that parallels the development of adult behaviors. However, little is known regarding cortical development in the adult rat brain. We used magnetic resonance imaging (MRI) and histology to assess the impact of age on adult Wistar rat cortical thickness on postnatal day (P)80 and P220 as well as the effect of adolescent binge ethanol exposure on adult (P80) cortical thickness. MRI revealed changes in cortical thickness between P80 and P220 that differ across cortical region. The adult P220 rat prefrontal cortex increased in thickness whereas cortical thinning occurred in both the cingulate and parietal cortices relative to young adult P80 rats. Histological analysis confirmed the age-related cortical thinning. In the second series of experiments, an animal model of adolescent intermittent ethanol (AIE; 5.0 g/kg, intragastrically, 20 percent ethanol w/v, 2 days on/2 days off from P25 to P55) was used to assess the effects of alcohol on cortical thickness in young adult (P80) rats. MRI revealed that AIE resulted in region-specific cortical changes. A small region within the prefrontal cortex was significantly thinner whereas medial cortical regions were significantly thicker in young adult (P80) AIE-treated rats. The observed increase in cortical thickness was confirmed by histology. Thus, the rat cerebral cortex continues to undergo cortical thickness changes into adulthood, and adolescent alcohol exposure alters the young adult cortex that could contribute to brain dysfunction in adulthood. PMID- 26833869 TI - The Dog that Didn't Bark in the Night-Time. PMID- 26833868 TI - Epigenetic Control of the Vasopressin Promoter Explains Physiological Ability to Regulate Vasopressin Transcription in Dehydration and Salt Loading States in the Rat. AB - The synthesis of arginine vasopressin (AVP) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) of the hypothalamus is sensitive to increased plasma osmolality and a decreased blood volume, and thus is robustly increased by both dehydration (increased plasma osmolality and decreased blood volume) and salt loading (increased plasma osmolality). Both stimuli result in functional remodelling of the SON and PVN, a process referred to as functional-related plasticity. Such plastic changes in the brain have recently been associated with altered patterns of DNA methylation at CpG (cytosine-phosphate-guanine) residues, a process considered to be important for the regulation of gene transcription. In this regard, the proximal Avp promoter contains a number of CpG sites and is recognised as one of four CpG islands for the Avp gene, suggesting that methylation may be regulating Avp transcription. In the present study, we show that, in an immortalised hypothalamic cell line 4B, the proximal Avp promoter is highly methylated, and treatment of these cells with the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine to demethylate DNA dramatically increases basal and stimulated Avp biosynthesis. We report no changes in the expression of DNA methyltransferases, Dnmt1 and Dnmt3a, whereas there is decreased expression of the demethylating enzyme ten-eleven-translocation 2, Tet2, in the SON by dehydration and salt loading. We found higher methylation of the SON Avp promoter in dehydrated but not salt-loaded rats. By analysis of individual CpG sites, we observed hypomethylation, hypermethylation and no change in methylation of specific CpGs in the SON Avp promoter of the dehydrated rat. Using reporter gene assays, we show that mutation of individual CpGs can result in altered Avp promoter activity. We propose that methylation of the SON Avp promoter is necessary to co-ordinate the duel inputs of increased plasma osmolality and decreased blood volume on Avp transcription in the chronically dehydrated rat. PMID- 26833870 TI - Evaluation of an injectable thermoresponsive hyaluronan hydrogel in a rabbit osteochondral defect model. AB - Articular cartilage displays very little self-healing capabilities, generating a major clinical need. Here, we introduce a thermoresponsive hyaluronan hydrogel for cartilage repair obtained by covalently grafting poly(N-isopropylacrylamide) to hyaluronan, to give a brush co-polymer HpN. The gel is fluid at room temperature and becomes gel at body temperature. In this pilot study HpN safety and repair response were evaluated in an osteochondral defect model in rabbit. Follow-up was of 1 week and 12 weeks and the empty defect served as a control, for a total of four experimental groups. At 12 weeks the defect sites were evaluated macroscopically and histologically. Local lymph nodes, spleen, liver, and kidneys were analyzed for histopathological evaluation. HpN could be easily injected and remained into the defect throughout the study. The macroscopic score was statistically superior for HpN versus empty. Histological score gave opposite trend but not statistically significant. A slight tissue reaction was observed around HpN, however, vascularization and subchondral bone formation were not impeded. An upper proteoglycans rich fibro-cartilaginous tissue with fairly good continuity and lateral integration into the existing articular cartilage was observed in all cases. No signs of local or systemic acute or subacute toxicity were observed. In conclusion, HpN is easily injectable, remains into an osteochondral defect within a moving synovial joint, is biocompatible and does not interfere with the intrinsic healing response of osteochondral defects in a rabbit model. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1469-1478, 2016. PMID- 26833871 TI - A weighted U statistic for association analyses considering genetic heterogeneity. AB - Converging evidence suggests that common complex diseases with the same or similar clinical manifestations could have different underlying genetic etiologies. While current research interests have shifted toward uncovering rare variants and structural variations predisposing to human diseases, the impact of heterogeneity in genetic studies of complex diseases has been largely overlooked. Most of the existing statistical methods assume the disease under investigation has a homogeneous genetic effect and could, therefore, have low power if the disease undergoes heterogeneous pathophysiological and etiological processes. In this paper, we propose a heterogeneity-weighted U (HWU) method for association analyses considering genetic heterogeneity. HWU can be applied to various types of phenotypes (e.g., binary and continuous) and is computationally efficient for high-dimensional genetic data. Through simulations, we showed the advantage of HWU when the underlying genetic etiology of a disease was heterogeneous, as well as the robustness of HWU against different model assumptions (e.g., phenotype distributions). Using HWU, we conducted a genome-wide analysis of nicotine dependence from the Study of Addiction: Genetics and Environments dataset. The genome-wide analysis of nearly one million genetic markers took 7h, identifying heterogeneous effects of two new genes (i.e., CYP3A5 and IKBKB) on nicotine dependence. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833872 TI - Editorial Comment to Association between levels of urinary heavy metals and increased risk of urothelial carcinoma. PMID- 26833877 TI - Bandgap Engineering of Lead-Halide Perovskite-Type Ferroelectrics. AB - Semiconducting ferroelectricity is realized in hybrid perovskite-type compounds (cyclohexylammonium)2 PbBr4-4 x I4 x (x = 0-1). By adjusting the composition x, the bandgap is successfully tuned from previously reported 3.65 eV to as low as 2.74 eV, and the excellent ferroelectricity was kept intact. This finding may contribute to improving the photoelectronic and/or photovoltaic performance of hybrid perovskite-type compounds. PMID- 26833879 TI - FGF2 regulates proliferation, migration, and invasion of ECA109 cells through PI3K/Akt signalling pathway in vitro. AB - Esophageal cancer is one of the most common malignant cancers that arise from esophagus tissues. Fibroblast growth factor 2 (FGF2) has been implicated in multiple biological functions and was considered as an oncogenic factor in tumorigenesis. However, the effects of FGF2 in esophageal carcinoma are yet to be fully elucidated. To better understand the function of FGF2 in esophageal cancer, we used the esophageal cancer cell line ECA109 as a cell model and downregulated FGF2 expression using RNAi; the results showed that insufficient expression of FGF2 inhibited cells proliferation, migration, and invasion of ECA109 cells. Meanwhile, the proliferation, migration, and invasion abilities were stimulated after treatment of exogenous FGF2. In addition, a PI3K/Akt signalling pathway inhibitor (LY294002) alleviated the tumorigenic effects of FGF2. These findings implied that the oncogenic effects of FGF2 was mediated, at least in part, through the PI3K/Akt signalling pathway and FGF2 may be a potential therapeutic target to constrain the tumorigenesis of esophageal cancer. PMID- 26833880 TI - A Versatile CuII Metal-Organic Framework Exhibiting High Gas Storage Capacity with Selectivity for CO2 : Conversion of CO2 to Cyclic Carbonate and Other Catalytic Abilities. AB - A linear tetracarboxylic acid ligand, H4 L, with a pendent amine moiety solvothermally forms two isostructural metal-organic frameworks (MOFs) LM (M=ZnII , CuII ). Framework LCu can also be obtained from LZn by post- synthetic metathesis without losing crystallinity. Compared with LZn , the LCu framework exhibits high thermal stability and allows removal of guest solvent and metal bound water molecules to afford the highly porous, LCu '. At 77 K, LCu ' absorbs 2.57 wt % of H2 at 1 bar, which increases significantly to 4.67 wt % at 36 bar. The framework absorbs substantially high amounts of methane (238.38 cm3 g-1 , 17.03 wt %) at 303 K and 60 bar. The CH4 absorption at 303 K gives a total volumetric capacity of 166 cm3 (STP) cm-3 at 35 bar (223.25 cm3 g-1 , 15.95 wt %). Interestingly, the NH2 groups in the linker, which decorate the channel surface, allow a remarkable 39.0 wt % of CO2 to be absorbed at 1 bar and 273 K, which comes within the dominion of the most famous MOFs for CO2 absorption. Also, LCu ' shows pronounced selectivity for CO2 absorption over CH4 , N2 , and H2 at 273 K. The absorbed CO2 can be converted to value-added cyclic carbonates under relatively mild reaction conditions (20 bar, 120 degrees C). Finally, LCu ' is found to be an excellent heterogeneous catalyst in regioselective 1,3-dipolar cycloaddition reactions ("click" reactions) and provides an efficient, economic route for the one-pot synthesis of structurally divergent propargylamines through three-component coupling of alkynes, amines, and aldehydes. PMID- 26833881 TI - Specific detection of Pectobacterium carotovorum by loop-mediated isothermal amplification. AB - Potatoes are an important agroeconomic crop worldwide and maceration diseases caused by pectolytic bacterial pathogens result in significant pre- and post harvest losses. Pectobacterium carotovorum shares a common host range with other Pectobacterium spp. and other members of the Enterobacteriaceae, such as Dickeya spp. As these pathogens cannot be clearly differentiated on the basis of the symptoms they cause, improved methods of identification are critical for the determination of sources of contamination. Current standardized methods for the differentiation of pectolytic species are time consuming and require trained personnel, as they rely on traditional bacteriological practices that do not always produce conclusive results. In this growing world market, there is a need for rapid diagnostic tests that can differentiate between pectolytic pathogens, as well as separate them from non-pectolytic enteric bacteria associated with soft rots of potato. An assay has been designed previously to detect the temperate pathogen Pectobacterium atrosepticum, but there is currently no recognized rapid assay for the detection of the tropical/subtropical counterpart, Pectobacterium carotovorum. This report describes the development of a loop mediated isothermal amplification (LAMP) assay that detects P. carotovorum with high specificity. The assay was evaluated using all known species of Pectobacterium and only showed positive reactions for P. carotovorum. This assay was also tested against 15 non-target genera of plant-associated bacteria and did not produce any false positives. The LAMP assay described here can be used as a rapid test for the differentiation of P. carotovorum from other pectolytic pathogens, and its gene target can be the basis for the development of other molecular-based detection assays. PMID- 26833878 TI - Stereoselective Halogenation in Natural Product Synthesis. AB - At last count, nearly 5000 halogenated natural products have been discovered. In approximately half of these compounds, the carbon atom to which the halogen is bound is sp(3) -hybridized; therefore, there are an enormous number of natural products for which stereocontrolled halogenation must be a critical component of any synthesis strategy. In this Review, we critically discuss the methods and strategies used for stereoselective introduction of halogen atoms in the context of natural product synthesis. Using the successes of the past, we also attempt to identify gaps in our synthesis technology that would aid the synthesis of halogenated natural products, as well as existing methods that have not yet seen application in complex molecule synthesis. The chemistry described herein demonstrates yet again how natural products continue to provide the inspiration for critical advances in chemical synthesis. PMID- 26833883 TI - Multiferroicity Broken by Commensurate Magnetic Ordering in Terbium Orthomanganite. AB - TbMnO3 is an important multiferroic material with strong coupling between magnetic and ferroelectric orderings. Incommensurate magnetic ordering is suggested to be vital for this coupling in TbMnO3 , which can be modified by doping at the site of Tb and/or Mn. Our study shows that a self-doped solid solution Tb1-x Mny MnO3 (y<=x) can be formed with Mn doped into the site of Tb of TbMnO3 . When y is small Tb1-x Mny MnO3 shows both ferroelectric and incommensurate magnetic orders at low temperature, which is similar to TbMnO3 . However, if y is large enough, a commensurate antiferromagnetic ordering appears along with the incommensurate magnetic ordering to prevent the appearance of multiferroicity in Tb1-x Mny MnO3 . That is to say, the magnetoeletric coupling can be broken by the co-existence of a commensurate antiferromagnetic ordering. This finding may be useful to the study of TbMnO3 . PMID- 26833882 TI - Not going with the flow: a comprehensive time-calibrated phylogeny of dragonflies (Anisoptera: Odonata: Insecta) provides evidence for the role of lentic habitats on diversification. AB - Ecological diversification of aquatic insects has long been suspected to have been driven by differences in freshwater habitats, which can be classified into flowing (lotic) waters and standing (lentic) waters. The contrasting characteristics of lotic and lentic freshwater systems imply different ecological constraints on their inhabitants. The ephemeral and discontinuous character of most lentic water bodies may encourage dispersal by lentic species in turn reducing geographical isolation among populations. Hence, speciation probability would be lower in lentic species. Here, we assess the impact of habitat use on diversification patterns in dragonflies (Anisoptera: Odonata). Based on the eight nuclear and mitochondrial genes, we inferred species diversification with a model based evolutionary framework, to account for rate variation through time and among lineages and to estimate the impact of larval habitat on the potentially nonrandom diversification among anisopteran groups. Ancestral state reconstruction revealed lotic fresh water systems as their original primary habitat, while lentic waters have been colonized independently in Aeshnidae, Corduliidae and Libellulidae. Furthermore, our results indicate a positive correlation of speciation and lentic habitat colonization by dragonflies: speciation rates increased in lentic Aeshnidae and Libellulidae, whereas they remain mostly uniform among lotic groups. This contradicts the hypothesis of inherently lower speciation in lentic groups and suggests species with larger ranges are more likely to diversify, perhaps due to higher probability of larger areas being dissected by geographical barriers. Furthermore, larger range sizes may comprise more habitat types, which could also promote speciation by providing additional niches, allowing the coexistence of emerging species. PMID- 26833884 TI - h-BN Nanosheets as 2D Substrates to Load 0D Fe3O4 Nanoparticles: A Hybrid Anode Material for Lithium-Ion Batteries. AB - h-BN, as an isoelectronic analogue of graphene, has improved thermal mechanical properties. Moreover, the liquid-phase production of h-BN is greener since harmful oxidants/reductants are unnecessary. Here we report a novel hybrid architecture by employing h-BN nanosheets as 2D substrates to load 0D Fe3O4 nanoparticles, followed by phenol/formol carbonization to form a carbon coating. The resulting carbon-encapsulated h-BN@Fe3O4 hybrid architecture exhibits synergistic interactions: 1) The h-BN nanosheets act as flexible 2D substrates to accommodate the volume change of the Fe3O4 nanoparticles; 2) The Fe3O4 nanoparticles serve as active materials to contribute to a high specific capacity; and 3) The carbon coating not only protects the hybrid architecture from deformation but also keeps the whole electrode highly conductive. The synergistic interactions translate into significantly enhanced electrochemical performances, laying a basis for the development of superior hybrid anode materials. PMID- 26833886 TI - Successful treatment of paradoxical darkening. AB - BACKGROUND AND OBJECTIVES: Tattoo removal can inadvertently lead to paradoxical darkening after laser procedure. We present a new laser device that may treat this unwanted outcome. STUDY DESIGN/PATIENTS AND METHODS: We report two cases from a clinical trial, using a novel picosecond 532 nm and 1,064 nm laser to treat unwanted red tattoos. RESULTS: Two cases of paradoxical darkening improved with the use of a novel picosecond 532 nm and 1,064 nm laser. CONCLUSION: The use of a picosecond 532 nm and 1,064 nm laser may treat paradoxical darkening in red colored tattoos. Lasers Surg. Med. 48:471-473, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26833888 TI - Cannabidiol disrupts the reconsolidation of contextual drug-associated memories in Wistar rats. AB - In addicts, craving and relapse are frequently induced by the recall of memories related to a drug experience. Several studies have demonstrated that drug-related memories are reactivated after exposure to environmental cues and may undergo reconsolidation, a process that can strengthen memories. Thus, reactivation of mnemonic traces provides an opportunity for disrupting memories that contribute to the pathological cycle of addiction. Here we used drug-induced conditioned place preference (CPP) to investigate whether cannabidiol (CBD), a phytocannabinoid, given just after reactivation sessions, would affect reconsolidation of drug-reward memory, reinstatement of morphine-CPP, or conditioned place aversion precipitated by naltrexone in Wistar rats. We found that CBD impaired the reconsolidation of preference for the environment previously paired with both morphine and cocaine. This disruption seems to be persistent, as the preference did not return after further reinstatement induced by priming drug and stress reinstatement. Moreover, in an established morphine CPP, an injection of CBD after the exposure to a conditioning session led to a significant reduction of both morphine-CPP and subsequent conditioned place aversion precipitated by naltrexone in the same context. Thus, established memories induced by a drug of abuse can be blocked after reactivation of the drug experience. Taken together, these results provide evidence for the disruptive effect of CBD on reconsolidation of contextual drug-related memories and highlight its therapeutic potential to attenuate contextual memories associated with drugs of abuse and consequently to reduce the risk of relapse. PMID- 26833885 TI - SGK1 is modulated by resistin in vascular smooth muscle cells and in the aorta following diet-induced obesity. AB - OBJECTIVE: Enhanced serum and glucocorticoid-inducible kinase 1 (SGK1) activity contributes to the pathogenesis of vascular disease. This study evaluated SGK1 modulation in vascular smooth muscle cells by the adipokine resistin and in aortic tissue in a murine model of diet-induced obesity (DIO). METHODS: Modulation of SGK1 by resistin was assessed in human aortic smooth muscle cells (HAoSMC) in vitro by quantitative RT-PCR and Western blot analyses. To induce the lean or obese phenotype, mice were fed a 10 kcal% low-fat or 60 kcal% high-fat diet, respectively, for 8 weeks. Upon study completion, plasma resistin was assessed and aortic tissue was harvested to examine the effect of DIO on regulation of SGK1 in vivo. RESULTS: Resistin increased SGK1 mRNA, total protein abundance, and its activation as determined by phosphorylation of its serine 422 residue (pSGK1) in HAoSMC. Resistin-mediated SGK1 phosphorylation was dependent upon phosphatidylinositol-3-kinase and Toll-like receptor 4. Furthermore, inhibition of SGK1 attenuated resistin-induced proliferation in HAoSMC. DIO led to up-regulation of total SGK1 protein levels and pSGK1 in association with increased plasma resistin. CONCLUSIONS: These data suggest that high levels of resistin observed during obesity may activate SGK1 in the vasculature and contribute to the development of obesity-related vascular disease. PMID- 26833887 TI - Efficacy and safety of catheter-based rheolytic and aspiration thrombectomy in children. AB - BACKGROUND: Vascular thromboses are a significant cause of morbidity and mortality in children. Data in children regarding catheter-based rheolytic and aspiration thrombectomy systems are limited. We sought to review the safety and efficacy of catheter-based rheolytic and aspiration thrombectomy systems in children. METHODS: Data of all children having undergone thrombectomy using specialized rheolytic or aspiration systems were reviewed. RESULTS: Thrombectomy was performed in 50 vessels in 21 patients, median age 1.9 months (8 days-18 yrs), median weight 4.3 (1.1-67.9) kg. Thrombectomy was performed using AngioJet in 16, Helix Clot Buster in 5, Fetch catheter in 8, Pronto catheter in 1, and a combination of other systems in 20 vessels (with AngioJet in 16). Thrombectomy was successful in 47/50 (94%) vessels in 18/21 (86%) patients with additional balloon/stent therapy or tPA administration performed in 16/18 (89%) of these patients. There were 2 (9.5%) major complications (both with AngioJet) consisting of asystole when thrombectomy was performed using activation times of >5 sec. At a median follow-up of 10 months (2 weeks-7 years), all 47 successfully treated vessels are patent, with 8/18 (44%) patients requiring reintervention with angioplasty/stent placement or repeat thrombectomy. CONCLUSIONS: Catheter-based thrombectomy systems are an important adjunctive tool in the treatment of children with thrombotic vessel occlusions. Significant hemodynamic compromise seen when using AngioJet may be minimized by using activation times of <=5 sec. (c) 2016 Wiley Periodicals, Inc. PMID- 26833889 TI - Community validation of the IDEA study cognitive screen in rural Tanzania. AB - OBJECTIVES: The dementia diagnosis gap in sub-Saharan Africa (SSA) is large, partly because of difficulties in screening for cognitive impairment in the community. As part of the Identification and Intervention for Dementia in Elderly Africans (IDEA) study, we aimed to validate the IDEA cognitive screen in a community-based sample in rural Tanzania METHODS: Study participants were recruited from people who attended screening days held in villages within the rural Hai district of Tanzania. Criterion validity was assessed against the gold standard clinical dementia diagnosis using DSM-IV criteria. Construct validity was assessed against, age, education, sex and grip strength and instrumental activities of daily living (IADLs). Internal consistency and floor and ceiling effects were also examined. RESULTS: During community screening, the IDEA cognitive screen had high criterion validity, with an area under the receiver operating characteristic curve of 0.855 (95% CI 0.794 to 0.915). Higher scores on the screen were significantly correlated with lower age, male sex, having attended school, better grip strength and improved performance in activities of daily living. Factor analysis revealed a single factor with an eigenvalue greater than one, although internal consistency was only moderate (Cronbach's alpha = 0.534). CONCLUSIONS: The IDEA cognitive screen had high criterion and construct validity and is suitable for use as a cognitive screening instrument in a community setting in SSA. Only moderate internal consistency may partly reflect the multi-domain nature of dementia as diagnosed clinically. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833890 TI - Synthesis, Biological Evaluation, and Molecular Docking of 8-imino-2-oxo-2H,8H pyrano[2,3-f]chromene Analogs: New Dual AChE Inhibitors as Potential Drugs for the Treatment of Alzheimer's Disease. AB - Alzheimer's disease onset and progression are associated with the dysregulation of multiple and complex physiological processes, and a successful therapeutic approach should therefore address more than one target. In line with this modern paradigm, a series of 8-imino-2-oxo-2H,8H-pyrano[2,3-f]chromene analogs (4a-q) were synthesized and evaluated for their multitarget-directed activity on acetylcholinesterase, butyrylcholinesterase (BuChE), 2,2'-azino-bis(3 ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical, and amyloid-beta peptide (Abeta) specific targets for Alzheimer's disease therapy. Most of the synthesized compounds showed remarkable acetylcholinesterase inhibitory activities in low nm concentrations and good ABTS radical scavenging activity, however, no evidence of BuChE inhibitory activity. Among them, 3-bromobenzylamide derivative 4m exhibited the best acetylcholinesterase inhibitory activity with IC50 value of 13 +/- 1.4 nm which is 51-fold superior to galantamine, a reference drug. Kinetic and molecular docking studies indicated 4m as mixed-type inhibitor, binding simultaneously to catalytic active and peripheral anionic sites of acetylcholinesterase. Five compounds 4e, 4f, 4g, 4j, and 4k have shown 1.4- to 2.5-fold of higher antioxidant activities than trolox. Interestingly, the most active compound 4m demonstrated dosage-dependent acceleration of Abeta1-42 aggregation, which may reduce toxicity of oligomers. Overall, these results lead to discovery of fused tricyclic coumarins as promising dual binding site inhibitors of acetylcholinesterase and afford multifunctional compounds with potential impact for further pharmacological development in Alzheimer's therapy. PMID- 26833892 TI - The 'Seven deadly sins' of rejected papers. PMID- 26833891 TI - Layer-by-layer coating of textile with two oppositely charged cyclodextrin polyelectrolytes for extended drug delivery. AB - The coating of a nonwoven textile by polyelectrolyte multilayer film (PEM) issued from cationic and anionic beta-cyclodextrin (betaCD) polyelectrolytes according to the layer-by-layer (LbL) technique was successfully attempted. The tert-butyl benzoic acid (TBBA) was used as drug model to evaluate the loading capacity and sustained release properties of this PEM system. The build-up of the multilayer assembly was monitored in situ by optical waveguide lightmode spectroscopy (OWLS) on the one hand, and was assessed by gravimetry on the other hand when applied onto the textile substrate. In parallel, the complexation study of TBBA with both CD polyelectrolytes was also investigated by nuclear magnetic resonance (NMR) and isothermal titration calorimetry (ITC). The influence of thermal crosslinking of the multilayered coating on its stability and on TBBA release kinetics in phosphate buffered saline (PBS) at 37 degrees C was studied. Finally, biological and microbiological tests were performed to investigate the cytocompatibility and the intrisic antibacterial activity of multilayer assemblies. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1408-1424, 2016. PMID- 26833893 TI - Propensity score matching with clustered data. An application to the estimation of the impact of caesarean section on the Apgar score. AB - This article focuses on the implementation of propensity score matching for clustered data. Different approaches to reduce bias due to cluster-level confounders are considered and compared using Monte Carlo simulations. We investigated methods that exploit the clustered structure of the data in two ways: in the estimation of the propensity score model (through the inclusion of fixed or random effects) or in the implementation of the matching algorithm. In addition to a pure within-cluster matching, we also assessed the performance of a new approach, 'preferential' within-cluster matching. This approach first searches for control units to be matched to treated units within the same cluster. If matching is not possible within-cluster, then the algorithm searches in other clusters. All considered approaches successfully reduced the bias due to the omission of a cluster-level confounder. The preferential within-cluster matching approach, combining the advantages of within-cluster and between-cluster matching, showed a relatively good performance both in the presence of big and small clusters, and it was often the best method. An important advantage of this approach is that it reduces the number of unmatched units as compared with a pure within-cluster matching. We applied these methods to the estimation of the effect of caesarean section on the Apgar score using birth register data. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833894 TI - Effects of Salt Loading on the Regulation of Rat Hypothalamic Magnocellular Neurosecretory Cells by Ionotropic GABA and Glycine Receptors. AB - Synaptic and extrasynaptic transmission mediated by ionotropic GABA and glycine receptors plays a critical role in shaping the action potential firing (spiking) activity of hypothalamic magnocellular neurosecretory cells and therefore determines the rate at which vasopressin and oxytocin are released from the neurohypophysis. The inhibitory effect of these transmitters relies on the maintenance of a low concentration of intracellular chloride ions such that, when activated by GABA or glycine, a hyperpolarisation of the neuronal membrane potential results. In this review, we highlight the various ways by which the two types of inhibitory receptors contribute to homeostasis by fine-tuning the spiking rate of vasopressin-releasing magnocellular neurosecretory cells in a manner dependent on the hydration state of the animal. In addition, we review the currently available evidence on how the strength of these inhibitory pathways can be regulated during chronic hypernatraemia via a form of activity-dependent depolarisation of the chloride reversal potential, leading to an abolition of these inhibitory pathways potentially causing sodium-dependent elevations in blood pressure. PMID- 26833895 TI - The male ScreenING Study: prevalence of HPV-related genital and anal lesions in an urban cohort of HIV-positive men in Germany. AB - BACKGROUND: Human papillomaviruses (HPV) induce condylomata, anogenital cancers and their precursor lesions as anal or penile intraepithelial neoplasia (AIN/PIN). HIV-positive individuals have an increased risk for the development of anogenital HPV-induced lesions. OBJECTIVE: Estimation of the prevalence of HPV related anogenital benign and malignant lesions in HIV-infected men attending a screening programme. METHODS: Four hundred HIV-positive men [98% men who have sex with men (MSM)] were enrolled in this prospective study from 2008 to 2011. All patients received an inspection of the anogenital region, digital rectal examination, high-resolution anoscopy (HRA), anal cytology, anal/penile histology if required, and HPV-typing of anal and penile swabs. RESULTS: At baseline, 75% (n = 302) of the men had abnormal anal cytological/histological results. 41% presented with low-grade (n = 164), 24% with high-grade anal dysplasia (n = 95) and two men with invasive anal cancer. 2.3% had PIN (n = 9) and one patient had penile cancer at baseline. Throughout the study period, 75% had anal dysplasia (low-grade n = 177, high-grade n = 125), 3.3% (n = 13) had PIN and two further patients developed anal cancer. Within the study period, 52.8% (n = 211) had condylomata (49% anal, 15% penile, 11% anal plus penile condylomata). At baseline, 88.5% of anal and 39.3% of penile swabs were HPV-DNA positive, and 77.8% of anal and 26.5% of penile swabs carried high-risk HPV-types. HPV16 was the most frequent HPV-type. CONCLUSION: HIV-positive MSM have a high risk for HPV induced condylomata, (pre)malignant anogenital lesions and anogenital cancers. Screening for HPV-induced dysplasia is crucial to avoid progression to invasive carcinomas. Additionally, HPV-vaccination recommendations should be extended to high-risk populations. PMID- 26833896 TI - Organic Light-Emitting Transistors: Materials, Device Configurations, and Operations. AB - Organic light-emitting transistors (OLETs) represent an emerging class of organic optoelectronic devices, wherein the electrical switching capability of organic field-effect transistors (OFETs) and the light-generation capability of organic light-emitting diodes (OLEDs) are inherently incorporated in a single device. In contrast to conventional OFETs and OLEDs, the planar device geometry and the versatile multifunctional nature of OLETs not only endow them with numerous technological opportunities in the frontier fields of highly integrated organic electronics, but also render them ideal scientific scaffolds to address the fundamental physical events of organic semiconductors and devices. This review article summarizes the recent advancements on OLETs in light of materials, device configurations, operation conditions, etc. Diverse state-of-the-art protocols, including bulk heterojunction, layered heterojunction and laterally arranged heterojunction structures, as well as asymmetric source-drain electrodes, and innovative dielectric layers, which have been developed for the construction of qualified OLETs and for shedding new and deep light on the working principles of OLETs, are highlighted by addressing representative paradigms. This review intends to provide readers with a deeper understanding of the design of future OLETs. PMID- 26833897 TI - Graphene Oxide-Based Electrode Inks for 3D-Printed Lithium-Ion Batteries. AB - All-component 3D-printed lithium-ion batteries are fabricated by printing graphene-oxide-based composite inks and solid-state gel polymer electrolyte. An entirely 3D-printed full cell features a high electrode mass loading of 18 mg cm( 2) , which is normalized to the overall area of the battery. This all-component printing can be extended to the fabrication of multidimensional/multiscale complex-structures of more energy-storage devices. PMID- 26833898 TI - Insights into 6-Methylsalicylic Acid Bio-assembly by Using Chemical Probes. AB - Chemical probes capable of reacting with KS (ketosynthase)-bound biosynthetic intermediates were utilized for the investigation of the model type I iterative polyketide synthase 6-methylsalicylic acid synthase (6-MSAS) in vivo and in vitro. From the fermentation of fungal and bacterial 6-MSAS hosts in the presence of chain termination probes, a full range of biosynthetic intermediates was isolated and characterized for the first time. Meanwhile, in vitro studies of recombinant 6-MSA synthases with both nonhydrolyzable and hydrolyzable substrate mimics have provided additional insights into substrate recognition, providing the basis for further exploration of the enzyme catalytic activities. PMID- 26833899 TI - A protease-activated receptor 2 agonist (AC-264613) suppresses interferon regulatory factor 5 and decreases interleukin-12p40 production by lipopolysaccharide-stimulated macrophages: Role of p53. AB - The transcription factor interferon regulatory factor 5 (IRF5) has a key role in the production of interleukin (IL)-12 by macrophages. IRF5 is also a central mediator of toll-like receptor signaling and is a direct target of p53. Activation of protease-activated receptor 2 (PAR-2) upregulates p53 and suppresses apoptosis. This study investigated the influence of human neutrophil elastase (HNE) and PAR-2 agonists on expression of IRF5 and IL-12p40 by macrophages stimulated with lipopolysaccharide. Granulocyte-macrophage colony stimulating factor (GM-CSF)-dependent macrophages showed upregulation of IRF5 expression, while HNE reduced expression of p53 and IRF5 in a concentration dependent manner. HNE also caused a concentration-dependent decrease of IRF5 in macrophages transfected with small interfering RNA to silence p53, while silencing of beta-arrestin 2 blunted the reduction of p53 or IRF5 by HNE. Incubation of macrophages with a PAR-2 agonist, AC-264613, caused a decrease of IRF5 expression and also significantly reduced p53 protein expression. HNE upregulated the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) and caused transactivation of TLR4, while AC-264613 did not promote TLR4 transactivation. In conclusion, the PAR-2 agonist AC-264613 attenuated IRF5 associated IL-12p40 production by macrophages. PMID- 26833900 TI - A Highly Reactive Geminal P/B Frustrated Lewis Pair: Expanding the Scope to C-X (X=Cl, Br) Bond Activation. AB - The geminal frustrated Lewis pair tBu2 PCH2 B(Fxyl)2 (1; Fxyl=3,5-(CF3 )2 C6 H3 ) is accessible in 65 % yield from tBu2 PCH2 Li and (Fxyl)2 BF. According to NMR spectroscopy and X-ray crystallography, 1 is monomeric both in solution and in the solid state. The intramolecular P???B distance of 2.900(5) A and the full planarity of the borane site exclude any significant P/B interaction. Compound 1 readily activates a broad variety of substrates including H2 , EtMe2 SiH, CO2 /CS2 , Ph2 CO, and H3 CCN. Terminal alkynes react with heterolysis of the C-H bond. Haloboranes give cyclic adducts with strong P-BX3 and weak R3 B-X bonds. Unprecedented transformations leading to zwitterionic XP/BCX3 adducts occur on treatment of 1 with CCl4 or CBr4 in Et2 O. In less polar solvents (C6 H6 , n pentane), XP/BCX3 adduct formation is accompanied by the generation of significant amounts of XP/BX adducts. FLP 1 catalyzes the hydrogenation of PhCH=NtBu and the hydrosilylation of Ph2 CO with EtMe2 SiH. PMID- 26833901 TI - Quorum sensing is a key regulator for the antifungal and biocontrol activity of chitinase-producing Chromobacterium sp. C61. AB - Chromobacterium sp. strain C61 has strong biocontrol activity; however, the genetic and biochemical determinants of its plant disease suppression activity are not well understood. Here, we report the identification and characterization of two new determinants of its biocontrol activity. Transposon mutagenesis was used to identify mutants that were deficient in fungal suppression. One of these mutants had an insertion in a homologue of depD, a structural gene in the dep operon, that encodes a protein involved in non-ribosomal peptide synthesis. In the second mutant, the insertion was in a homologue of the luxI gene, which encodes a homoserine lactone synthase. The luxI- and depD- mutants had no antifungal activity in vitro and a dramatically reduced capacity to suppress various plant diseases in planta. Antifungal production and biocontrol were restored by complementation of the luxI- mutant. Other phenotypes associated with effective biological control, including motility and lytic enzyme secretion, were also affected by the luxI mutation. Biochemical analysis of ethyl acetate extracts of culture filtrates of the mutant and wild-type strains showed that a key antifungal compound, chromobactomycin, was produced by wild-type C61 and the complemented luxI- mutant, but not by the luxI- or depD- mutant. These data suggest that multiple biocontrol-related phenotypes are regulated by homoserine lactones in C61. Thus, quorum sensing plays an essential role in the biological control potential of diverse bacterial lineages. PMID- 26833902 TI - Species-wide patterns of DNA methylation variation in Quercus lobata and their association with climate gradients. AB - DNA methylation in plants affects transposon silencing, transcriptional regulation and thus phenotypic variation. One unanswered question is whether DNA methylation could be involved in local adaptation of plant populations to their environments. If methylation alters phenotypes to improve plant response to the environment, then methylation sites or the genes that affect them could be a target of natural selection. Using reduced-representation bisulphite sequencing (RRBS) data, we assessed whether climate is associated with variation in DNA methylation levels among 58 naturally occurring, and species-wide samples of valley oak (Quercus lobata) collected across climate gradients. We identified the genomic context of these variants referencing a new draft valley oak genome sequence. Methylation data were obtained for 341 107 cytosines, of which we deemed 57 488 as single-methylation variants (SMVs), found in the CG, CHG and CHH sequence contexts. Environmental association analyses revealed 43 specific SMVs that are significantly associated with any of four climate variables, the majority of which are associated with mean maximum temperature. The 43 climate associated SMVs tend to occur in or near genes, several of which have known involvement in plant response to environment. Multivariate analyses show that climate and spatial variables explain more overall variance in CG-SMVs among individuals than in SNPs, CHG-SMVs or CHH-SMVs. Together, these results from natural oak populations provide initial evidence for a role of CG methylation in locally adaptive evolution or plasticity in plant response. PMID- 26833903 TI - Coupling Electrochemistry with Probe Electrospray Ionization Mass Spectrometry. AB - A new coupling of electrochemistry with mass spectrometry (MS) using probe electrospray ionization (PESI) is presented. Due to the high salt tolerance of PESI, the detection of electrochemical reaction products in room-temperature ionic liquids (RTILs) is realized for the first time. Furthermore, PESI-MS allows the analysis of electrochemical reaction products on different or multiple electrode surfaces. In addition, peptides and proteins fractionated through isoelectric focusing (IEF) in the presence of an external electric field can also be directly analyzed by using PESI-MS, suggesting a new and rapid characterization means for the IEF technique. This study reveals the versatility of EC/PESI-MS, which could have an impact in electrochemistry and bioanalysis fields. PMID- 26833904 TI - Bipyridinium Polymers That Dock Tetrathiafulvalene Guests in Water Driven by Donor-Acceptor and Ion Pair Interactions. AB - Two water-soluble para-xylylene-connected 4,4'-bipyridinium (BIPY(2+) ) polymers have been prepared. UV-Vis absorption, (1) H NMR spectroscopy, and cyclic voltammetry experiments support that in water the BIPY(2+) units in the polymers form stable 1:1 charge-transfer complexes with tetrathiafulvalene (TTF) guests that bear two or four carboxylate groups. These charge-transfer complexes are stabilized by the donor-acceptor interaction between electron-rich TTF and electron-deficient BIPY(2+) units and electrostatic attraction between the dicationic BIPY(2+) units and the anionic carboxylate groups attached to the TTF core. On the basis of UV-Vis experiments, a lower limit to the apparent association constant of the TTF?BIPY(2+) complexes of the mixtures, 1.8*10(6) m( 1) , has been estimated in water. Control experiments reveal substantially reduced binding ability of the neutral TTF di- and tetracarboxylic acids to the BIPY(2+) molecules and polymers. Moreover, the stability of the charge-transfer complexes formed by the BIPY(2+) units of the polymers are considerably higher than that of the complexes formed between two monomeric BIPY(2+) controls and the dicarboxylate-TTF donor; this has been attributed to the mutually strengthened electron-deficient nature of the BIPY(2+) units of the polymers due to the electron-withdrawing effect of the BIPY(2+) units. PMID- 26833906 TI - 2015 Kocemba-Slosky Fellowship. PMID- 26833905 TI - Platelet lysate supports the in vitro expansion of human periodontal ligament stem cells for cytotherapeutic use. AB - Human platelet lysate (PL) produced under optimal conditions of standardization and safety has been increasingly suggested as the future 'gold standard' supplement to replace fetal bovine serum (FBS) for the ex vivo propagation of mesenchymal stem cells for translational medicine and cell therapy applications. However, the multifaceted effects of PL on tissue-specific stem cells remain largely unexplored. In the present study, we investigated the stem cell behaviours of human periodontal ligament stem cells (PDLSCs) in media with or without PL. Our data indicate that human PL, either as an adjuvant for culture media or as a substitute for FBS, supports the proliferation and expansion of human PDLSCs derived from either 'young' or 'old' donors to the same extent as FBS, without interfering with their immunomodulatory capacities. Although PL appears to inhibit the in vitro differentiation of 'young' or 'old' PDLSCs, their decreased osteogenic potential may be restored to similar or higher levels compared with FBS-expanded cells. PL- and FBS-expanded PDLSCs exhibited a similar potential to form mineralized nodules and expressed similar levels of osteogenic genes. Our data indicate that large clinically relevant quantities of PDLSCs may be yielded by the use of human PL; however, further analysis of its precise composition and function will pave the way for determining optimized, defined culture conditions. In addition to the potential increase in patient safety, our findings highlight the need for further research to develop the potential of PL expanded PDLSCs for clinical use. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833907 TI - In Memoriam: Alan Davison, PhD, 1936-2015. PMID- 26833908 TI - Looking to the Future: The ABNM in the Next 10 Years. PMID- 26833909 TI - SNMMI Leadership Update: Clinical Trials Network Update. PMID- 26833914 TI - The bicaudate index inversely associates with performance in the Montreal Cognitive Assessment (MoCA) in older adults living in rural Ecuador. The Atahualpa project. AB - OBJECTIVE: Assessment of cognitive impairment in rural areas of developing countries is complicated by illiteracy and cross-cultural factors. A better way to estimate the usefulness of cognitive screening instruments is to evaluate their correlation with imaging biomarkers. The bicaudate index (a marker of central atrophy) correlates with cognitive performance. We assessed the relationship of the bicaudate index with the MoCA to estimate the usefulness of this test to detect individuals with cognitive decline in these regions. METHODS: Atahualpa residents aged >=60 years identified during door-to-door surveys were evaluated with the MoCA and invited to undergo brain MRI. Using generalized linear models, we estimated whether the bicaudate index correlates with MoCA scores, after adjusting for demographics and relevant clinical and neuroimaging confounders. RESULTS: Out of 385 eligible persons, 290 (75%) were enrolled. Mean bicaudate index was 0.14 +/- 0.03, and mean total MoCA score was 19 +/- 5 points. Locally weighted scatterplot smoothing showed a nearly linear inverse relationship between the bicaudate index and the total MoCA score. In the fully adjusted generalized linear model, the bicaudate index was inversely associated with the total MoCA score (p < 0.001), which dropped by 5.3% (95% C.I.: 1.7% 8.8%) for every standard deviation of the bicaudate index. In addition, most domain-specific MoCA scores were inversely associated with the bicaudate index. CONCLUSIONS: The inverse relationship between the bicaudate index and the MoCA score provides evidence that the MoCA is reliable to detect structural brain damage and useful to assess cognitive performance in less educated individuals. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833915 TI - HIV RNA and proviral HIV DNA can be detected in semen after 6 months of antiretroviral therapy although HIV RNA is undetectable in blood. AB - The risk of sexual transmission of HIV is strongly correlated with amounts of genital HIV RNA. Few studies have reported amounts of HIV RNA and HIV DNA in semen in HIV-infected Chinese patients undergoing antiviral treatment (ART). In this observational study, the amounts of HIV RNA and HIV DNA in semen were assessed after six months of ART in HIV-infected Chinese individuals, when HIV RNA was undetectable in blood . This study included 19 HIV-infected Chinese men undergoing ART for six months. Amounts of HIV in paired semen and blood samples were assessed using real-time PCR. The C2-V5 region of the HIV envelope (env) genes was cloned and sequenced and genotype and co-receptor usage predicted based on the sequence. It was found that HIV RNA was undetectable in the plasma of most patients (17/19), whereas HIV RNA could be detected in the semen of most patients (16/19). HIV DNA could be detected in both semen and blood. Genetic diversity of HIV between the seminal and blood compartments was identified. Thus, amounts of HIV RNA and HIV DNA remain high in semen of HIV-infected Chinese patients after six months of ART treatment, even when HIV RNA was undetectable in blood. PMID- 26833916 TI - Prognostic impact of the residual SYNTAX score on in-hospital outcomes in patients undergoing primary percutaneous coronary intervention. AB - OBJECTIVES: This study sought to assess the impact of residual coronary artery disease (CAD), using the residual SYNTAX score (rSS), on in-hospital outcomes after primary percutaneous intervention (PPCI). The study also aimed to determine independent predictors for high rSS. Residual CAD has been associated with worsened prognosis in patients undergoing PCI for non-ST acute coronary syndromes. The rSS is a systematic angiographic score that measures the extent and complexity of residual CAD after PCI. MATERIALS AND METHODS: Data from 243 consecutive patients undergoing PPCI for ST-elevation myocardial infarction (STEMI) were analyzed. The rSS was derived from post-PPCI angiography. Patients were dichotomized into low (<8) and high rSS (>=8) groups and outcomes were compared between groups. The primary outcome of net adverse cardiovascular events (NACE) consisted of a composite of in-hospital death, congestive heart failure (CHF), recurrent MI and bleeding. RESULTS: The mean rSS was 4.7 (+/-7.2). A high rSS was associated with the primary outcome (P < 0.0001), in-hospital death (P = 0.0026), periprocedural death (P < 0.0001), CHF (P < 0.0004) and acute kidney injury (P < 0.0019). A high rSS was also an independent predictor of the primary outcome with an OR of 3.82. Independent predictors of a high rSS included a history of diabetes (OR 2.8), previous MI (OR 5.75), 2-vessel disease (VD) (OR 15.48, vs. 1-VD) and 3-VD (OR 57.06, vs. 1-VD). CONCLUSIONS: Residual CAD, as assessed by the rSS, confers a worsened prognosis in patients undergoing PPCI. Diabetes, previous MI and multi-vessel disease were independent predictors of a high rSS. (c) 2016 Wiley Periodicals, Inc. PMID- 26833913 TI - Expression of functional cannabinoid CB2 receptor in VTA dopamine neurons in rats. AB - We have recently reported the expression of functional cannabinoid CB2 receptors (CB2 Rs) in midbrain dopamine (DA) neurons in mice. However, little is known whether CB2 Rs are similarly expressed in rat brain because significant species differences in CB2 R structures and expression are found. In situ hybridization and immunohistochemical assays detected CB2 gene and receptors in DA neurons of the ventral tegmental area (VTA), which was up-regulated in cocaine self administration rats. Electrophysiological studies demonstrated that activation of CB2 Rs by JWH133 inhibited VTA DA neuronal firing in single dissociated neurons. Systemic administration of JWH133 failed to alter, while local administration of JWH133 into the nucleus accumbens inhibited cocaine-enhanced extracellular DA and i.v. cocaine self-administration. This effect was blocked by AM630, a selective CB2 R antagonist. These data suggest that CB2 Rs are expressed in VTA DA neurons and functionally modulate DA neuronal activities and cocaine self-administration behavior in rats. PMID- 26833917 TI - Human mesostriatal response tracks motivational tendencies under naturalistic goal conflict. AB - Goal conflict situations, involving the simultaneous presence of reward and punishment, occur commonly in real life, and reflect well-known individual differences in the behavioral tendency to approach or avoid. However, despite accumulating neural depiction of motivational processing, the investigation of naturalistic approach behavior and its interplay with individual tendencies is remarkably lacking. We developed a novel ecological interactive scenario which triggers motivational behavior under high or low goal conflict conditions. Fifty five healthy subjects played the game during a functional magnetic resonance imaging scan. A machine-learning approach was applied to classify approach/avoidance behaviors during the game. To achieve an independent measure of individual tendencies, an integrative profile was composed from three established theoretical models. Results demonstrated that approach under high relative to low conflict involved increased activity in the ventral tegmental area (VTA), peri-aquaductal gray, ventral striatum (VS) and precuneus. Notably, only VS and VTA activations during high conflict discriminated between approach/avoidance personality profiles, suggesting that the relationship between individual personality and naturalistic motivational tendencies is uniquely associated with the mesostriatal pathway. VTA-VS further demonstrated stronger coupling during high vs low conflict. These findings are the first to unravel the multilevel relationship among personality profile, approach tendencies in naturalistic set-up and their underlying neural manifestation, thus enabling new avenues for investigating approach-related psychopathologies. PMID- 26833920 TI - Identification of copy number variations associated with congenital heart disease by chromosomal microarray analysis and next-generation sequencing. AB - OBJECTIVE: To determine the type and frequency of pathogenic chromosomal abnormalities in fetuses diagnosed with congenital heart disease (CHD) using chromosomal microarray analysis (CMA) and validate next-generation sequencing as an alternative diagnostic method. METHOD: Chromosomal aneuploidies and submicroscopic copy number variations (CNVs) were identified in amniocytes DNA samples from CHD fetuses using high-resolution CMA and copy number variation sequencing (CNV-Seq). RESULT: Overall, 21 of 115 CHD fetuses (18.3%) referred for CMA had a pathogenic chromosomal anomaly. In six of 73 fetuses (8.2%) with an isolated CHD, CMA identified two cases of DiGeorge syndrome, and one case each of 1q21.1 microdeletion, 16p11.2 microdeletion and Angelman/Prader Willi syndromes, and 22q11.21 microduplication syndrome. In 12 of 42 fetuses (28.6%) with CHD and additional structural abnormalities, CMA identified eight whole or partial trisomies (19.0%), five CNVs (11.9%) associated with DiGeorge, Wolf-Hirschhorn, Miller-Dieker, Cri du Chat and Blepharophimosis, Ptosis, and Epicanthus Inversus syndromes and four other rare pathogenic CNVs (9.5%). Overall, there was a 100% diagnostic concordance between CMA and CNV-Seq for detecting all 21 pathogenic chromosomal abnormalities associated with CHD. CONCLUSION: CMA and CNV-Seq are reliable and accurate prenatal techniques for identifying pathogenic fetal chromosomal abnormalities associated with cardiac defects. (c) 2016 John Wiley & Sons, Ltd. PMID- 26833918 TI - Alterations of amygdala-prefrontal connectivity with real-time fMRI neurofeedback in BPD patients. AB - With the use of real-time functional magnetic resonance imaging neurofeedback (NF), amygdala activitiy can be visualized in real time. In this study, continuous amygdala NF was provided to patients with borderline personality disorder (BPD) with the instruction to down-regulate. During four sessions of NF training, patients viewed aversive pictures and received feedback from a thermometer display, which showed the amygdala blood oxygenation level-dependent signal. Conditions of regulation and viewing without regulation were presented. Each session started with a resting-state scan and was followed by a transfer run without NF. Amygdala regulation, task-related and resting-state functional brain connectivity were analyzed. Self-ratings of dissociation and difficulty in emotion regulation were collected. BPD patients down-regulated right amygdala activation but there were no improvements over time. Task-related amygdala ventromedial prefrontal cortex connectivity was altered across the four sessions, with an increased connectivity when regulating vs viewing pictures. Resting-state amygdala-lateral prefrontal cortex connectivity was altered and dissociation, as well as scores for 'lack of emotional awareness', decreased with training. Results demonstrated that amygdala NF may improve healthy brain connectivity, as well as emotion regulation. A randomized-controlled trial is needed to investigate whether amygdala NF is instrumental for improving neural regulation and emotion regulation in BPD patients. PMID- 26833919 TI - Positive mood enhances reward-related neural activity. AB - Although behavioral research has shown that positive mood leads to desired outcomes in nearly every major life domain, no studies have directly examined the effects of positive mood on the neural processes underlying reward-related affect and goal-directed behavior. To address this gap, participants in the present fMRI study experienced either a positive (n = 20) or neutral (n = 20) mood induction and subsequently completed a monetary incentive delay task that assessed reward and loss processing. Consistent with prediction, positive mood elevated activity specifically during reward anticipation in corticostriatal neural regions that have been implicated in reward processing and goal-directed behavior, including the nucleus accumbens, caudate, lateral orbitofrontal cortex and putamen, as well as related paralimbic regions, including the anterior insula and ventromedial prefrontal cortex. These effects were not observed during reward outcome, loss anticipation or loss outcome. Critically, this is the first study to report that positive mood enhances reward-related neural activity. Our findings have implications for uncovering the neural mechanisms by which positive mood enhances goal-directed behavior, understanding the malleability of reward-related neural activity, and developing targeted treatments for psychiatric disorders characterized by deficits in reward processing. PMID- 26833922 TI - The rapid enrollment design for Phase I clinical trials. AB - We propose a dose-finding design for Phase I oncology trials where each new patient is assigned to the dose most likely to be the target dose given observed data. The main model assumption is that the dose-toxicity curve is non decreasing. This method is beneficial when it is desirable to assign a patient to a dose as soon as the patient is enrolled into a study. To prevent assignments to doses with limited toxicity information in fast accruing trials we propose a conservative rule that assigns temporary fractional toxicities to patients still in follow-up. We also recommend always using a safety rule in any fast accruing dose-finding trial. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833924 TI - Bundled payment is coming: It is time for NPs to get involved. PMID- 26833921 TI - Structure Effect of Some New Anticancer Pt(II) Complexes of Amino Acid Derivatives with Small Branched or Linear Hydrocarbon Chains on Their DNA Interaction. AB - The aim of this study was to investigate the structure effect and identify the modes of binding of amino acid-Pt complexes to DNA molecule for cancer treatment. Hence, three novel water soluble platinum complexes, [Pt(phen)(R-gly)]NO3 (where phen is 1,10-phenanthroline, R-gly is methyl, amyl, and isopentyl-glycine), have been synthesized and characterized by spectroscopic methods, conductivity measurements, and chemical analysis. The anticancer activities of synthesized complexes were investigated against human breast cancer cell line of MDA-MB 231. The 50% cytotoxic concentration values were determined to be 42.5, 58, and 70 MUm for methyl-, amyl-, and isopentyl-gly complexes, respectively. These complexes were interacted with calf thymus DNA (ct-DNA) via positive cooperative interaction. The modes of binding of the complexes to DNA were investigated by fluorescence spectroscopy and circular dichroism in combination with a molecular docking study. The result indicates that complexes with small or branched hydrocarbon chains can intercalate with DNA. This is while amyl complexes with linear chains interacted additionally via groove binding. The results of the negative value of Gibbs energy for binding of isopentyl-platinum to DNA and those of the molecular docking were coherent. Furthermore, the docking results demonstrated that hydrophobic interaction plays an important role in the complex DNA interaction. PMID- 26833925 TI - Difference between early onset and late-onset pediatric ulcerative colitis. AB - BACKGROUND: Early onset pediatric ulcerative colitis (EO-UC) is distinguished from late-onset pediatric ulcerative colitis (LO-UC) by the effects of genetic predisposition, but there have been few reports on the clinical features of EO-UC in Asia. METHODS: To describe and compare the presentation and disease course of EO-UC (age range, 0-7 years) with those of LO-UC (age range, 8-15 years), we retrospectively analyzed 63 children with UC who had been diagnosed between January 2004 and March 2014 at Saitama Children's Medical Center in Japan. RESULTS: Ten patients (16%) had EO-UC, and 53 (84%) had LO-UC. All patients in the EO-UC group and 70% in the LO-UC group had pancolitis (P = 0.05). The period from onset to diagnosis was 9.0 +/- 14.1 months for EO-UC and 2.6 +/- 3.5 months for LO-UC (P < 0.01). The prevalence of extra-intestinal complications at diagnosis was significantly higher for EO-UC than for LO-UC (50% vs 11%, respectively; P < 0.01). There were no significant differences in the use of corticosteroids, immunomodulators, immunosuppressants, or surgical risk between the groups but, in the EO-UC group, only one patient was treated with cytapheresis and none was treated with anti-tumor necrosis factor (TNF-alpha) antibodies. CONCLUSIONS: The EO-UC group had a higher incidence of pancolitis, longer diagnostic delay, and more extra-intestinal manifestations than the LO-UC group. Diagnosis and treatment may therefore be slightly more difficult for EO-UC than for LO-UC. PMID- 26833926 TI - Direct Observation of Localized Radial Oxygen Migration in Functioning Tantalum Oxide Memristors. AB - Oxygen migration in tantalum oxide, a promising next-generation storage material, is studied using in operando X-ray absorption spectromicroscopy. This approach allows a physical description of the evolution of conduction channel and eventual device failure. The observed ring-like patterns of oxygen concentration are modeled using thermophoretic forces and Fick diffusion, establishing the critical role of temperature-driven oxygen migration. PMID- 26833927 TI - A novel heterozygous mutation in desmoplakin gene in a Lebanese patient with Carvajal syndrome and tooth agenesis. PMID- 26833928 TI - The influence of a learning to forgive programme on negative affect among mentally disordered offenders. AB - BACKGROUND: Clinical trials and meta-analyses provide some evidence for effectiveness of forgiveness therapy delivered individually or in groups. To date, however, forgiveness therapy has not been evaluated with mentally disordered offenders. Given the high prevalence of experienced and perpetrated trauma among such people, this population may particularly benefit from such an intervention. AIM: The aim of this study is to test the feasibility and impact of a 'learn to forgive' group programme among mentally disordered offenders on a specialist secure hospital setting. METHODS: We conducted a non-randomised trial with 36 offenders with mental disorders and 29 comparison patients. The intervention group engaged in a six-week manual-based 'learn to forgive' treatment programme, while the comparison group watched a 90-minute video on forgiveness. Both groups completed measures of anger, depression, stress, forgiveness and satisfaction with life at baseline and then 6 and 18 weeks later. A repeated measures mixed-effects model was used to investigate the association between affective outcomes and type of intervention received, after adjusting for baseline characteristics. RESULTS: The group completion rate was over 90%. The treatment and comparison groups were similar on baseline demographic and criminological measures, but the treatment group had higher baseline anger and depression scores. While both groups showed improved capacity to forgive and reduced negative affect over time, those in the 'learn to forgive' programme showed significantly more improvement in forgiveness and on anger measures. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Forgiveness training can be delivered effectively to offenders with mental disorders in clinical settings. Its range of benefits, including reduction I in anger as well as improved capacity to forgive, suggest that it may have longer term implications for personal safety and reintegration into mainstream societal settings. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833929 TI - Assessing the needs of caregivers of children with disabilities in Penang, Malaysia. AB - Disability in a child not only affects the child but also presents socioeconomic and psychological impacts to the child's family. This study aims to describe the service needs of caregivers of children with disabilities in the state of Penang, Malaysia, and to determine the child and family characteristics predisposing to having more caregiver needs. A cross-sectional survey was conducted between February and June 2013 among caregivers of children aged 0-12 years with disabilities registered with the Penang Department of Social Welfare. Caregivers completed a self-administered mailed questionnaire containing a 20-item Caregiver Needs Scale (CNS). Each item in the CNS was rated on a 5-point Likert scale ranging from 'help not at all needed' to 'help extremely needed'. A total of 273 surveys were available for analysis (response rate 34.0%). The CNS contained four domains. The 'Help getting Information and Services for child' domain had the highest mean score (3.61, 95% CI: 3.46, 3.77) followed by 'Help with Finances' (3.29, 95% CI: 3.13, 3.45) and 'Help Coping with child' (3.11, 95% CI: 2.97, 3.25), while the 'Help getting Childcare' domain had the lowest mean score (2.30, 95% CI: 2.13, 2.47). Multivariate regression analysis identified caregivers of younger children and with more severe disability as having more caregiver needs in all domains. Besides that, caregivers of children with learning disability needed more help getting information and help with coping. Caregivers of children with learning and multiple disabilities needed more help getting childcare compared to children with other disability. Caregivers of Indian ethnicity, who had less than a tertiary education and who themselves had medical problems needed more help with finances. The findings on caregiver needs in this study can help inform planning of family support services for children with disabilities in Penang, Malaysia. PMID- 26833930 TI - Structural brain correlates of cognitive and behavioral impairment in MND. AB - OBJECTIVE: To assess the structural correlates of cognitive and behavioral impairment in motor neuron diseases (MND) using multimodal MRI. METHODS: One hundred one patients with sporadic MND (56 classic amyotrophic lateral sclerosis, 31 upper motor neuron phenotype, and 14 lower motor neuron phenotype) and 51 controls were enrolled. Patients were classified into MND with a pure motor syndrome (MND-motor) and with cognitive/behavioral symptoms (MND-plus). Cortical thickness measures and diffusion tensor (DT) metrics of white matter (WM) tracts were assessed. A random forest approach was used to explore the independent role of cortical and WM abnormalities in explaining major cognitive and behavioral symptoms. RESULTS: There were 48 MND-motor and 53 MND-plus patients. Relative to controls, both patient groups showed a distributed cortical thinning of the bilateral precentral gyrus, insular and cingulate cortices, and frontotemporal regions. In all regions, there was a trend toward a more severe involvement in MND-plus cases, particularly in the temporal lobes. Both patient groups showed damage to the motor callosal fibers, which was more severe in MND-plus. MND-plus patients also showed a more severe involvement of the extra-motor WM tracts. The best predictors of executive and non-executive deficits and behavioral symptoms in MND were diffusivity abnormalities of the corpus callosum and frontotemporal tracts, including the uncinate, cingulum, and superior longitudinal fasciculi. CONCLUSIONS: Cortical thinning and WM degeneration are highly associated with neuropsychological and behavioral symptoms in patients with MND. DT MRI metrics seem to be the most sensitive markers of extra-motor deficits within the MND spectrum. PMID- 26833931 TI - Integration of Multiple Plasmonic and Co-Catalyst Nanostructures on TiO2 Nanosheets for Visible-Near-Infrared Photocatalytic Hydrogen Evolution. AB - Utilization of visible and near-infrared light has always been the pursuit of photocatalysis research. In this article, an approach is developed to integrate dual plasmonic nanostructures with TiO2 semiconductor nanosheets for photocatalytic hydrogen production in visible and near-infrared spectral regions. Specifically, the Au nanocubes and nanocages used in this work can harvest visible and near-infrared light, respectively, and generate and inject hot electrons into TiO2 . Meanwhile, Pd nanocubes that can trap the energetic electrons from TiO2 and efficiently participate in the hydrogen evolution reaction are employed as co-catalysts for improved catalytic activity. Enabled by this unique integration design, the hydrogen production rate achieved is dramatically higher than those of its counterpart structures. This work represents a step toward the rational design of semiconductor-metal hybrid structures for broad-spectrum photocatalysis. PMID- 26833932 TI - The meaning of illness in nursing practice: a philosophical model of communication and concept possession. AB - It is fundamental assumption in nursing theory that it is important for nurses to understand how patients experience states of ill health. This assumption is often related to aims of empathic understanding, but normative principles of social interpretation can have an important action-guiding role whenever nurses seek to understand patients' subjective horizons on the basis of active or passive expressions of meaning. The aim of this article is to present a philosophical theory of concept possession and to argue that it can shed light on how nurses should seek to understand patients' subjective perspectives on the meaning of illness. The two basic ideas in the theory are that patients' beliefs and thoughts about their experiences involve concepts and that concepts can be communicated on the basis of shared implicit conceptions of what they mean. These conditions of understanding have a striking application: nurse-patient communication is limited by many contextual factors, but it is often possible for nurses to detect shared implicit conceptions of the meaning of concepts of disease and illness. Furthermore, by acting as sympathetic linguistic experts and creating an atmosphere for dialogue, nurses can make patients feel comfortable about deferring to medical explanations of meaning that can constitute a communicative platform. The last part of the article uses a number of cases studies to show how these implications can be implemented as conceptual tools for securing meaningful communication about illness experiences in patient dialogue. PMID- 26833933 TI - Impact of caregiver readiness on outcomes of a nonpharmacological intervention to address behavioral symptoms in persons with dementia. AB - BACKGROUND: Previous research shows that nonpharmacological strategies may effectively manage behavioral symptoms (agitation, wandering) in persons with dementia and improve caregiver wellbeing. However, strategies depend upon caregivers for their implementation. We examine the impact of caregiver readiness to use nonpharmacological strategies on treatment outcomes. METHODS: Data were from a randomized trial involving 110 family caregivers in the treatment group which received nonpharmacologic strategies for managing behavioral symptoms. Interventionists rated caregiver readiness to use nonpharmacologic strategies as pre-action (precontemplation, contemplation, preparation) or action at treatment initiation and conclusion. Caregivers in pre-action and action stages by treatment conclusion (16 weeks) were compared on proximal (frequency of, and caregiver upset and confidence with targeted behaviors) and more distal (caregiver burden and wellbeing) outcomes at 16 and 24-week follow-ups. RESULTS: By treatment conclusion, 28.2% (n = 31) and 71.8% (n = 79) of caregivers were rated at pre-action and action respectively. Means for proximal outcomes differed between the groups at 16 and 24 weeks; those at action showed greater improvement on all proximal and distal outcomes. Hierarchical regressions showed significant relationships of readiness to targeted outcomes. By 24 weeks, caregiver readiness predicted lower frequency estimates of targeted behaviors (beta = -.180, p = .041) and higher confidence (beta = .27, p = .009). Readiness was not a significant predictor of caregiver burden and wellbeing at 16 or 24 weeks. CONCLUSION: By treatment conclusion, >25% of participants were not activated to use nonpharmacologic strategies. Activated caregivers reported greater decline in distressing behavioral symptoms, and more confidence than non-activated participants. Activation is needed to impact behavioral management but not other caregiver outcomes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833934 TI - Comparison of instructor-led versus peer-led debriefing in nursing students. AB - Despite its widespread support, the most effective simulation-based debriefing method has little evidence to support its efficacy. In this study, we compared the effect of peer-led and instructor-led debriefing among nursing students. The study was conducted with a non-equivalent control group using a pretest-post-test design. A convenience sample of third-year nursing students was used for the study, where 65 students enrolled in a 2-week clinical placement rotation were randomly assigned to the instructor-led group or peer-led group. The quality of cardiopulmonary resuscitation skills, satisfaction with simulation, and quality of debriefing in the peer-led group were compared to those in the instructor-led group. Group differences at each testing interval were analyzed using independent t-test. Nursing students in the instructor-led debriefing group showed better subsequent cardiopulmonary resuscitation performance, more satisfaction with simulation experience, and higher debriefing scores compared to the peer-led group. From our study, instructor-led debriefing is an effective method in improving skills performance, inducing favorable satisfaction, and providing better quality of debriefing among nursing students. PMID- 26833935 TI - Quantitative multi-image analysis for biomedical Raman spectroscopic imaging. AB - Imaging by Raman spectroscopy enables unparalleled label-free insights into cell and tissue composition at the molecular level. With established approaches limited to single image analysis, there are currently no general guidelines or consensus on how to quantify biochemical components across multiple Raman images. Here, we describe a broadly applicable methodology for the combination of multiple Raman images into a single image for analysis. This is achieved by removing image specific background interference, unfolding the series of Raman images into a single dataset, and normalisation of each Raman spectrum to render comparable Raman images. Multivariate image analysis is finally applied to derive the contributing 'pure' biochemical spectra for relative quantification. We present our methodology using four independently measured Raman images of control cells and four images of cells treated with strontium ions from substituted bioactive glass. We show that the relative biochemical distribution per area of the cells can be quantified. In addition, using k-means clustering, we are able to discriminate between the two cell types over multiple Raman images. This study shows a streamlined quantitative multi-image analysis tool for improving cell/tissue characterisation and opens new avenues in biomedical Raman spectroscopic imaging. PMID- 26833936 TI - Determination of silicone rubber and low-density polyethylene diffusion and polymer/water partition coefficients for emerging contaminants. AB - There is a growing interest in assessing the concentration and distribution of new nonregulated organic compounds (emerging contaminants) in the environment. The measurement of freely dissolved concentrations using conventional approaches is challenging because of the low concentrations that may be encountered and their temporally variable emissions. Absorption-based passive sampling enables the estimation of freely dissolved concentrations of hydrophobic contaminants of emerging concern in water. In the present study, calibration was undertaken for 2 polymers, low-density polyethylene (LDPE) and silicone rubber for 11 fragrances, 5 endocrine-disrupting compounds, 7 ultraviolet (UV) filters, and 8 organophosphate flame retardant compounds. Batch experiments were performed to estimate contaminant diffusion coefficients in the polymers (Dp ), which in general decreased with increasing molecular weight. The values for fragrances, endocrine-disrupting compounds, and UV filters were in ranges similar to those previously reported for polycyclic aromatic hydrocarbons, but were 1 order of magnitude lower for organophosphate flame retardant compounds. Silicone rubber had higher Dp values than LDPE and was therefore selected for further experiments to calculate polymer/water partition coefficients (KPW ). The authors observed a positive correlation between log KPW and log octanol/water partition coefficient values. Field testing of silicone rubber passive samplers was undertaken though exposure in the River Alna (Norway) for an exposure time of 21 d to estimate freely dissolved concentration. Some fragrances and UV filters were predominant over other emerging and regulated contaminants, at levels up to 1600 ng L(-1) for galaxolide and 448 ng L(-1) for octocrylene. Environ Toxicol Chem 2016;35:2162 2172. (c) 2016 SETAC. PMID- 26833938 TI - Tau, amyloid, and hypometabolism in the logopenic variant of primary progressive aphasia. PMID- 26833937 TI - Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. AB - OBJECTIVE: To update the 2005 American Academy of Neurology (AAN) guideline on corticosteroid treatment of Duchenne muscular dystrophy (DMD). METHODS: We systematically reviewed the literature from January 2004 to July 2014 using the AAN classification scheme for therapeutic articles and predicated recommendations on the strength of the evidence. RESULTS: Thirty-four studies met inclusion criteria. RECOMMENDATIONS: In children with DMD, prednisone should be offered for improving strength (Level B) and pulmonary function (Level B). Prednisone may be offered for improving timed motor function (Level C), reducing the need for scoliosis surgery (Level C), and delaying cardiomyopathy onset by 18 years of age (Level C). Deflazacort may be offered for improving strength and timed motor function and delaying age at loss of ambulation by 1.4-2.5 years (Level C). Deflazacort may be offered for improving pulmonary function, reducing the need for scoliosis surgery, delaying cardiomyopathy onset, and increasing survival at 5-15 years of follow-up (Level C for each). Deflazacort and prednisone may be equivalent in improving motor function (Level C). Prednisone may be associated with greater weight gain in the first years of treatment than deflazacort (Level C). Deflazacort may be associated with a greater risk of cataracts than prednisone (Level C). The preferred dosing regimen of prednisone is 0.75 mg/kg/d (Level B). Over 12 months, prednisone 10 mg/kg/weekend is equally effective (Level B), with no long-term data available. Prednisone 0.75 mg/kg/d is associated with significant risk of weight gain, hirsutism, and cushingoid appearance (Level B). PMID- 26833939 TI - Bilateral occipital strokes from an atherosclerotic trigeminal artery. PMID- 26833940 TI - International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. PMID- 26833941 TI - Association of atrial fibrillation with mortality and disability after ischemic stroke. PMID- 26833942 TI - Pearls & Oy-sters: Localization in acute stroke management: Thinking straight when it comes down to crunch time. PMID- 26833943 TI - Clinical Reasoning: An 11-year-old boy with language disorder and epilepsy. PMID- 26833944 TI - Teaching Video NeuroImages: Daytime sleepiness and automatic behavior due to severe restless legs syndrome. PMID- 26833945 TI - Monolayer Filaments versus Multilayer Stacking of Bent-Core Molecules. AB - Bent-core materials exhibiting lamellar crystals (B4 phase), when dissolved in organic solvents, formed gels with helical ribbons made of molecular monolayers and bilayers, whereas strongly deformed stacks of 5-6 layers were found in the bulk samples. The width and pitch of the helical filaments were governed by molecular length; they both increased with terminal-chain elongation. It was also found that bulk samples were optically active, in contrast to the corresponding gels, which lacked optical activity. The optical activity of samples originated from the internal structure of the crystal layers rather than from the helicity of the filaments. A theoretical model predicts a strong increase in optical activity as the number of layers in the stack increases and its saturation for few layers, thus explaining the smaller optical activity for gels than for bulk samples. A strong increase and redshift in fluorescence was detected in gels as compared to the sol state. PMID- 26833946 TI - Genetic complementation analysis showed distinct contributions of the N-terminal tail of H2A.Z to epigenetic regulations. AB - H2A.Z is one of the most evolutionally conserved histone variants. In vertebrates, this histone variant has two isoforms, H2A.Z.1 and H2A.Z.2, each of which is coded by an individual gene. H2A.Z is involved in multiple epigenetic regulations, and in humans, it also has relevance to carcinogenesis. In this study, we used the H2A.Z DKO cells, in which both H2A.Z isoform genes could be inducibly knocked out, for the functional analysis of H2A.Z by a genetic complementation assay, as the first example of its kind in vertebrates. Ectopically expressed wild-type H2A.Z and two N-terminal mutants, a nonacetylable H2A.Z mutant and a chimera in which the N-terminal tail of H2A.Z.1 was replaced with that of the canonical H2A, complemented the mitotic defects of H2A.Z DKO cells similarly, suggesting that both acetylation and distinctive sequence of the N-terminal tail of H2A.Z are not required for mitotic progression. In contrast, each one of these three forms of H2A.Z complemented the transcriptional defects of H2A.Z DKO cells differently. These results suggest that the N-terminal tail of vertebrate H2A.Z makes distinctively different contributions to these epigenetic events. Our results also imply that this genetic complementation system is a novel and useful tool for the functional analysis of H2A.Z. PMID- 26833947 TI - Carlino to the rescue: Use of intralesion contrast injection for bailout antegrade and retrograde crossing of complex chronic total occlusions. AB - Percutaneous coronary intervention (PCI) of coronary chronic total occlusions (CTO) can be challenging. Although several crossing techniques are available, in some cases their application fails to cross the occlusion. Carlino et al. have pioneered the technique of hydraulic microdissection by contrast injection through a microcatheter inserted into the lesion. We report two CTO PCI cases in which the use of the Carlino technique enabled success after other crossing strategies failed to cross the occlusion. (c) 2016 Wiley Periodicals, Inc. PMID- 26833948 TI - Characterization of human adipose tissue-derived stem cells with enhanced angiogenic and adipogenic properties. AB - Autologous fat grafting is a popular method for soft tissue reconstructions but graft survival remains highly unpredictable. Supplementation of the graft with the stromal vascular fraction (SVF) or cultured adipose tissue-derived stem cells (ASCs) can enhance graft viability. In this study we have examined the phenotypic properties of a selected population of cells isolated from ASCs, with a view to determining their suitability for transplantation into grafts. ASCs were isolated from the SVF of human abdominal fat (n = 8 female patients) and CD146+ cells were selected using immunomagnetic beads. The angiogenic and adipogenic properties of the positively selected cells were compared with the negative fraction. CD146+ cells expressed the immunophenotypic characteristics of pericytes. With prolonged in vitro expansion, CD146- cells exhibited increased population doubling times and morphological signs of senescence, whereas CD146+ cells did not. CD146+ cells expressed higher levels of the angiogenic molecules VEGF-A, angiopoietin-1 and FGF-1. Conditioned medium taken from CD146+ cells significantly increased formation of in vitro endothelial cell tube networks, whereas CD146- cells did not. CD146+ cells could be differentiated into adipocytes in greater numbers than CD146- cells. Consistent with this, differentiated CD146+ cells expressed higher levels of the adipocyte markers adiponectin and leptin. These results suggest that CD146+ cells selected from a heterogeneous mix of ASCs have more favourable angiogenic and adipogenic properties, which might provide significant benefits for reconstructive and tissue-engineering applications. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833949 TI - Parallel beta-sheet vibration band increases with proteins dipole moment under exposure to 1765 MHz microwaves. AB - Effects of exposure of 4 h to mobile phones microwaves at 1765 MHz at a power density around 940 mW/m(2) on four typical proteins (hemoglobin in H2 O solution, and myoglobin, bovine serum albumin, and lysozyme in D2 O solution) were studied by means of Fourier Transform Infrared spectroscopy and Fourier self deconvolution analysis. Increase in intensity of parallel beta-sheet component around 1635 cm(-1) was observed after exposure of hemoglobin, myoglobin, and bovine serum albumin, showing that a mechanism of unfolding occurred after exposure, whereas no appreciable change in the amide I region occurred after lysozyme exposure. In addition, a relationship between protein dipole moment and protein unfolding rate was demonstrated with a correlation coefficient r = 0.973 and 95% confidence interval. PMID- 26833950 TI - Bilateral and symmetric isolated dorsospinal arteries with prominent anterior radiculomedullary contribution. AB - We present the case of a 15-year-old girl with a left T7 spinal epidural arteriovenous fistula (SEAVF), in whom bilateral and symmetric isolated T9 dorsospinal arteries (DAs) were incidentally documented, each providing a significant contribution to the anterior spinal artery. Recognizing the existence of isolated DAs of direct aortic origin is critical, both for the diagnostic evaluation and for the management of spinal vascular diseases. Notably, isolated DAs tend to branch off significant radiculomedullary arteries, which vascularize the normal spinal cord but have also been shown to supply spinal vascular malformations. PMID- 26833953 TI - Combined ab interno trabeculotomy and lens extraction: a novel management option for combined uveitic and chronic narrow angle raised intraocular pressure. AB - Minimally invasive glaucoma surgery is a developing area that has the potential to replace traditional glaucoma surgery, with its known risk profile, but at present there are no randomised controlled data to validate its use. We report on a case where sequential bilateral combined ab interno trabeculotomy and lens extraction surgery was performed on a 45-year-old woman with combined uveitic and chronic narrow angle raised intraocular pressure. Maximal medical management alone could not control the intraocular pressure. At 12-month follow-up, the patient had achieved stable intraocular pressure in both eyes on a combination of topical ocular antiglaucomatous and steroid therapies. This case demonstrates the effectiveness of trabecular meshwork ablation via ab interno trabeculotomy in a case of complex mixed mechanism glaucoma. PMID- 26833951 TI - Cornelia de Lange and Ehlers-Danlos: comorbidity of two rare syndromes. AB - We present a case of a young adult with both Cornelia de Lange syndrome and Ehlers-Danlos syndrome. The patient showed non-verbal autism, intellectual disability and severe/intractable self-harming behaviours that led to a life threatening complication (ie, septicaemia). A significant reduction in the self harming behaviours was attained in a multidisciplinary neurobehavioural inpatient unit after addressing all causes of somatic pains, managing pain using level II and III analgesics, stabilising the patient's mood, limiting the iatrogenic effects of multiple prescriptions and offering a specific psychoeducational approach. PMID- 26833952 TI - Co-occurrence of biphenotypic acute leukaemia, glucose 6-phosphate dehydrogenase deficiency and haemoglobin E trait in a single child. AB - Acute leukaemias occur as the result of clonal expansion subsequent to transformation and arrest at a normal differentiation stage of haematopoietic precursors, which commit to a single lineage, such as myeloid or B-lymphoid or T lymphoid cells. Biphenotypic acute leukaemia (BAL) constitutes a biologically different group of leukaemia arising from a precursor stem cell and co-expressing more than one lineage specific marker. The present report describes a child with unusual co-occurrence of biphenotypic (B-precursor cell and Myeloid) acute leukaemia, haemoglobin E trait and glucose 6-phosphate dehydrogenase (G6-PD) deficiency. To the best of our knowledge, this constellation of haematological conditions in a single child has never been described before. PMID- 26833955 TI - Mesenteric lymphangioma mimicking a cystic ovarian mass on imaging. AB - Pelvic cystic masses are frequently observed in women. Most lesions are benign and of ovarian origin. However, non-ovarian lesions can be easily confused with cystic ovarian masses on imaging, which hampers diagnostic and therapeutic management. In this report, a rare case of mesenteric lymphangioma mimicking an ovarian cystic mass, discovered as an incidental finding on orthopaedic MRI in an adult female, is presented. The report highlights the sometimes difficult diagnostic process of pelvic cystic masses, due to an extensive differential diagnosis and the fact that imaging is often inconclusive. Even though most cystic masses are of ovarian origin, non-ovarian causes can mimic ovarian masses and should be considered as differential diagnoses. Surgical exploration may be necessary to exclude malignant causes. PMID- 26833956 TI - Two rare cases of appendiceal collision tumours involving an appendiceal mucinous neoplasm and carcinoid. AB - We report two rare cases of appendiceal collision tumours, each involving an appendiceal mucinous neoplasm with a concomitant appendiceal carcinoid. The first case presented with acute appendicitis while the second presented with an incidental radiological finding of an enlarged appendix as part of evaluation for raised serum carcinoembryonic antigen. Diagnosis in both cases was made postoperatively on histological assessment following appendicectomy. Clinical and histological features of both tumour types in each case did not necessitate further surgical resection or adjuvant treatment. Both patients did well postoperatively and had no evidence of disease recurrence on follow-up. PMID- 26833954 TI - Lifestyle medicine consulting walking meetings for sustained weight loss. AB - With rates of obesity and diabetes rising worldwide, effective ways of managing weight are becoming more important. We present the case study of a middle-aged Caucasian-American woman (body mass index (BMI) 27.8, overweight category) who wanted to lose weight. The patient participated in a behaviour modification programme with a physician trained in lifestyle medicine as well as health and wellness coaching. After the 14-week programme, which included 9, 1 h long walking sessions with the clinician, the patient lost 11 Ibs (BMI 24.7, normal category). The programme included a combination of increasing physical activity, eating appropriate quantities of healthy foods, goal setting and a positive attitude. The patient has kept her BMI at or below 24.1 for over 2 years. This case demonstrates a novel approach to weight loss management--walking therapeutic sessions--and also outlines critical components of lifestyle medicine counselling that facilitate the process of sustainable weight loss and lasting change. PMID- 26833957 TI - Design and analysis of clinical trials in the presence of delayed treatment effect. AB - In clinical trials with survival endpoint, it is common to observe an overlap between two Kaplan-Meier curves of treatment and control groups during the early stage of the trials, indicating a potential delayed treatment effect. Formulas have been derived for the asymptotic power of the log-rank test in the presence of delayed treatment effect and its accompanying sample size calculation. In this paper, we first reformulate the alternative hypothesis with the delayed treatment effect in a rescaled time domain, which can yield a simplified sample size formula for the log-rank test in this context. We further propose an intersection union test to examine the efficacy of treatment with delayed effect and show it to be more powerful than the log-rank test. Simulation studies are conducted to demonstrate the proposed methods. PMID- 26833958 TI - Long-term effects of pneumococcal colonization during early childhood wheezing. AB - BACKGROUND: Bacterial colonization during wheezing in early childhood has been associated with short-term relapses of wheezing, but no study has addressed the effects of Streptococcus pneumoniae colonization on long-term outcome of wheezing. The aim of the present study was therefore to evaluate whether pneumococcal (PNC) colonization during the first wheezing episode in early childhood is a determinant of asthma, atopy or lung function in the long term. METHODS: In 1981-82 83 infants were hospitalized for first wheezing episode at <24 months of age. PNC colonization was defined as positive nasopharyngeal aspirate for S. pneumoniae either in culture or antigen detection on hospital admission. Atopy and repeated wheezing or asthma were diagnosed on all follow-up visits from infancy until the age of 28-31 years. Spirometry was conducted at the ages of 8-10, 18-20 and 28-31 years. RESULTS: PNC colonization was found in 25/83 infants (30%) during hospitalization for wheezing in infancy. PNC colonization was not associated with later atopy, repeated wheezing, asthma or lung function at any time during the 30 year follow up. CONCLUSION: PNC colonization during the first wheezing episode in early childhood is not a determinant of subsequent wheezing or later asthma, atopy or lung function in childhood, adolescence or adulthood. PMID- 26833959 TI - Expression of exo-inulinase gene from Aspergillus niger 12 in E. coli strain Rosetta-gami B (DE3) and its characterization. AB - Inulin is a linear carbohydrate polymer of fructose subunits (2-60) with terminal glucose units, produced as carbon storage in selected plants. It cannot directly be taken up by most microorganisms due to its large size, unless prior hydrolysis through inulinase enzymes occurs. The hydrolyzed inulin can be taken up by microbes and/or recovered and used industrially for the production of high fructose syrup, inulo-oligosaccharides, biofuel, and nutraceuticals. Cell-free enzymatic hydrolysis would be desirable for industrial applications, hence the recombinant expression, purification and characterization of an Aspergillus niger derived exo-inulinase was investigated in this study. The eukaroyototic exo inulinase of Aspergillus niger 12 has been expressed, for the first time, in an E. coli strain [Rosetta-gami B (DE3)]. The molecular weight of recombinant exo inulinase was estimated to be ~81 kDa. The values of Km and Vmax of the recombinant exo-inulinase toward inulin were 5.3 +/- 1.1 mM and 402.1 +/- 53.1 umol min(-1) mg(-1) protein, respectively. Towards sucrose the corresponding values were 12.20 +/- 1.6 mM and 902.8 +/- 40.2 umol min(-1) mg(-1) protein towards sucrose. The S/I ratio was 2.24 +/- 0.7, which is in the range of native inulinase. The optimum temperature and pH of the recombinant exo-inulinase towards inulin was 55 degrees C and 5.0, while they were 50 degrees C and 5.5 towards sucrose. The recombinant exo-inulinase activity towards inulin was enhanced by Cu(2+) and reduced by Fe(2+) , while its activity towards sucrose was enhanced by Co(2+) and reduced by Zn(2+) . (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:629-637, 2016. PMID- 26833960 TI - Expanding the phenotypic profile of Kleefstra syndrome: A female with low-average intelligence and childhood apraxia of speech. AB - Kleefstra syndrome (KS) is a rare neurogenetic disorder most commonly caused by deletion in the 9q34.3 chromosomal region and is associated with intellectual disabilities, severe speech delay, and motor planning deficits. To our knowledge, this is the first patient (PQ, a 6-year-old female) with a 9q34.3 deletion who has near normal intelligence, and developmental dyspraxia with childhood apraxia of speech (CAS). At 6, the Wechsler Preschool and Primary Intelligence testing (WPPSI-III) revealed a Verbal IQ of 81 and Performance IQ of 79. The Beery Buktenica Test of Visual Motor Integration, 5th Edition (VMI) indicated severe visual motor deficits: VMI = 51; Visual Perception = 48; Motor Coordination < 45. On the Receptive One Word Picture Vocabulary Test-R (ROWPVT-R), she had standard scores of 96 and 99 in contrast to an Expressive One Word Picture Vocabulary-R (EOWPVT-R) standard scores of 73 and 82, revealing a discrepancy in vocabulary domains on both evaluations. Preschool Language Scale-4 (PLS-4) on PQ's first evaluation reveals a significant difference between auditory comprehension and expressive communication with standard scores of 78 and 57, respectively, further supporting the presence of CAS. This patient's near normal intelligence expands the phenotypic profile as well as the prognosis associated with KS. The identification of CAS in this patient provides a novel explanation for the previously reported speech delay and expressive language disorder. Further research is warranted on the impact of CAS on intelligence and behavioral outcome in KS. Therapeutic and prognostic implications are discussed. PMID- 26833961 TI - Stretchable and Multimodal All Graphene Electronic Skin. AB - A transparent and stretchable all-graphene multifunctional electronic-skin sensor matrix is developed. Three different functional sensors are included in this matrix: humidity, thermal, and pressure sensors. These are judiciously integrated into a layer-by-layer geometry through a simple lamination process. PMID- 26833962 TI - Role of cyclooxygenase inhibitors in aquagenic syringeal acrokeratoderma. PMID- 26833963 TI - Are Benner's expert nurses near extinction? PMID- 26833965 TI - Rapid determination of the volatile components in tobacco by ultrasound-microwave synergistic extraction coupled to headspace solid-phase microextraction with gas chromatography-mass spectrometry. AB - An ultrasound-microwave synergistic extraction coupled to headspace solid-phase microextraction was first employed to determine the volatile components in tobacco samples. The method combined the advantages of ultrasound, microwave, and headspace solid-phase microextraction. The extraction, separation, and enrichment were performed in a single step, which could greatly simplify the operation and reduce the whole pretreatment time. In the developed method, several experimental parameters, such as fiber type, ultrasound power, and irradiation time, were optimized to improve sampling efficiency. Under the optimal conditions, there were 37, 36, 34, and 36 components identified in tobacco from Guizhou, Hunan, Yunnan, and Zimbabwe, respectively, including esters, heterocycles, alkanes, ketones, terpenoids, acids, phenols, and alcohols. The compound types were roughly the same while the contents were varied from different origins due to the disparity of their growing conditions, such as soil, water, and climate. In addition, the ultrasound-microwave synergistic extraction coupled to headspace solid-phase microextraction method was compared with the microwave-assisted extraction coupled to headspace solid-phase microextraction and headspace solid phase microextraction methods. More types of volatile components were obtained by using the ultrasound-microwave synergistic extraction coupled to headspace solid phase microextraction method, moreover, the contents were high. The results indicated that the ultrasound-microwave synergistic extraction coupled to headspace solid-phase microextraction technique was a simple, time-saving and highly efficient approach, which was especially suitable for analysis of the volatile components in tobacco. PMID- 26833964 TI - The relationship between nurse staffing and length of stay in acute-care: a one year time-series data. AB - AIM: To examine the relationship between nurse staffing and patient length of stay in an acute-care hospital over a 1-year period. BACKGROUND: Although there has been prior research on the relationship between nurse staffing and length of stay in acute-care hospitals, there is a need for more information on how nurse staffing is related to length of stay longitudinally. METHODS: Retrospective time series registry data from 20 acute-care inpatient units of a Finnish university hospital as a monthly time series in 2008 were analysed by linear mixed models. RESULTS: The ratio of registered nurses to all nurses was 72.4%. Nurses worked mainly (96%) full time, and 63% had permanent employment contracts. Statistically significant variation was found in time series of five variables. Statistically significant relationships were found between length of stay and patient acuity, diagnosis-related group-volume, census and nursing hours per patient day at the unit level. Nursing hours per patient day had the strongest correlation with length of stay. CONCLUSION AND IMPLICATIONS FOR NURSING MANAGEMENT: A rational response to the variations in patient care needs and intensity in the complex care environment is flexible nurse staffing. Increasing nursing hours per patient day to achieve shorter length of stays is not the only solution, well-functioning care processes are also essential. PMID- 26833966 TI - Sex differences in the physiology of exercise: an integrative perspective. AB - Video slideshow introduction to the Symposium by Symposium Speaker A. William Sheel can be found here. PMID- 26833967 TI - The role of heart rate in the left ventricular twist response to increased arterial blood pressure: a 'stiff' challenge? PMID- 26833968 TI - Blast from the past! Phrenic motor memory of antecedent episodic hypercapnia is serotonin dependent: relevance to respiratory rehabilitation and sleep-disordered breathing? PMID- 26833969 TI - Structural MRI correlates of cognitive impairment in patients with multiple sclerosis: A Multicenter Study. AB - In a multicenter setting, we applied voxel-based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal-appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing-remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with >=2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel-wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty-three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive-relevant WM tracts followed by atrophy of cognitive-relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS. PMID- 26833970 TI - Is integrated care associated with service costs and admission rates to institutional settings? An observational study of community mental health teams for older people in England. AB - OBJECTIVES: To evaluate the association between the degree of integration in community mental health teams (CMHTs) and: (i) the costs of service provision; (ii) rates of mental health inpatient and care home admission. METHODS: An observational study of service use and admissions to institutional care was undertaken for a prospectively-sampled cohort of patients from eight CMHTs in England. Teams were chosen to represent 'high' or 'low' levels of integrated working practice and patients were followed-up for seven months. General linear models were used to estimate service costs and the likelihood of institutional admission. RESULTS: Patients supported by high integration teams received services costing an estimated 44% more than comparable patients in low integration teams. However, after controlling for case mix, no significant differences were found in the likelihood of admission to mental health inpatient wards or care homes between team types. CONCLUSIONS: Integrated mental health and social care teams appeared to facilitate greater access to community care services, but no consequent association was found with community tenure. Further research is required to identify the necessary and sufficient components of integrated community mental health care, and its effect on a wider range of outcomes using patient-reported measures. (c) 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd. PMID- 26833971 TI - Direct oral anticoagulants: New drugs with practical problems. How can nurses help prevent patient harm? AB - The safe use of anticoagulants requires a delicate balance between the risk of bleeding and the risk of thrombosis, particularly in drug-sensitive patients, such as older people. Recently-marketed "direct oral anticoagulants" are now being increasingly prescribed and administered in the hospital setting. Direct oral anticoagulants have pharmacological properties that are often unpredictable, and inter-patient variability in drug response is high. Therefore, people often require meticulous review and planning to ensure they receive optimal dosing and monitoring. The multidisciplinary medication management of those receiving these drugs needs to be effectively coordinated to reduce the risk of patient harm. All clinical staff, including nurses, doctors, and pharmacists, should be competent in the pharmacology of these drugs, and know which people require individualized care plans. In this study, we introduced important concepts via the use of case studies developed from commonly-seen scenarios at our quaternary hospital. In particular, the important role of nurses in ensuring patient safety in the periprocedural setting is highlighted. PMID- 26833972 TI - Design of Highly Selective Platinum Nanoparticle Catalysts for the Aerobic Oxidation of KA-Oil using Continuous-Flow Chemistry. AB - Highly active and selective aerobic oxidation of KA-oil to cyclohexanone (precursor for adipic acid and E-caprolactam) has been achieved in high yields using continuous-flow chemistry by utilizing uncapped noble-metal (Au, Pt & Pd) nanoparticle catalysts. These are prepared using a one-step in situ methodology, within three-dimensional porous molecular architectures, to afford robust heterogeneous catalysts. Detailed spectroscopic characterization of the nature of the active sites at the molecular level, coupled with aberration-corrected scanning transmission electron microscopy, reveals that the synthetic methodology and associated activation procedures play a vital role in regulating the morphology, shape and size of the metal nanoparticles. These active centers have a profound influence on the activation of molecular oxygen for selective catalytic oxidations. PMID- 26833974 TI - Nanomechanics of Poly(catecholamine) Coatings in Aqueous Solutions. AB - Mussel-inspired self-polymerized catecholamine coatings have been widely utilized as a versatile coating strategy that can be applied to a variety of substrates. For the first time, nanomechanical measurements and an evaluation of the contribution of primary amine groups to poly(catecholamine) coatings have been conducted using a surface-forces apparatus. The adhesive strength between the poly(catecholamine) layers is 30-times higher than that of a poly(catechol) coating. The origin of the strong attraction between the poly(catecholamine) layers is probably due to surface salt displacement by the primary amine, pi-pi stacking (the quadrupole-quadrupole interaction of indolic crosslinks), and cation-pi interactions (the monopole-quadrupole interaction between positively charged amine groups and the indolic crosslinks). The contribution of the primary amine group to the catecholamine coating is vital for the design and development of mussel-inspired catechol-based coating materials. PMID- 26833973 TI - The effect of low-intensity pulsed ultrasound on bone-tendon junction healing: Initiating after inflammation stage. AB - The purpose of this study was to explore the effect of low-intensity pulsed ultrasound (LIPUS) treatment initiating after inflammation stage on the process of bone-tendon junction (BTJ) healing in a rabbit model. Thirty-six rabbits undergoing partial patellectomy were randomly divided into two groups: control and LIPUS. The period of initial inflammatory stage is 2 weeks. So LIPUS treatment was initiated at postoperative week 2 and continued until the patella patellar tendon (PPT) complexes were harvested at postoperative weeks 4, 8, and 16. At each time point, the PPT complexes were harvested for qRT-PCR, histology, radiographs, synchroton radiation micro computed tomography (SR-uCT), and biomechanical testing. The qRT-PCR results showed that LIPUS treatment beginning at postoperative week 2 played an anti-inflammatory role in BTJ healing. Histologically, the LIPUS group showed more advanced remodeling of the lamellar bone and marrow cavity than the control group. The area and length of the new bone in the LIPUS group were significantly greater than the control group at postoperative weeks 8 and 16. SR-uCT demonstrated that new bone formation and remodeling in the LIPUS group were more advanced than the control group. Biomechanical test results demonstrated that the failure load, ultimate strength and energy at failure were significantly higher than those of the control group. In conclusion, LIPUS treatment beginning at postoperative week 2 was able to accelerate bone formation during the bone-tendon junction healing process and significantly improved the healing quality of BTJ injury. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1697-1706, 2016. PMID- 26833975 TI - Multiway analysis applied to time-resolved chemiluminescence for simultaneous determination of paracetamol and codeine in pharmaceuticals. AB - This method is based on the enhancing effect of codeine (COD) and paracetamol (PAR) on the chemiluminescence (CL) reaction of Ru(phen)3 (2+) with Ce(IV). In the batch mode, COD gives a relatively sharp peak with the highest CL intensity at 4.0 s, whereas the maximum CL intensity of the PAR appears at ~60 s after injection of Ce(IV) solution. Whole CL time profiles allowed use of the time resolved CL data in combination with multiway calibration techniques, as multiway partial least squares (N-PLS), for the quantitative determination of both COD and PAR in binary mixtures. In this work, we found that the impact of Ce(IV) concentration on the CL intensity was different for COD and PAR. Therefore, a Ce(IV) concentration mode was added to the time and sample modes to obtain 3D data. The percent relative standard deviation (%RSD) values for 10 determinations of 1.0 * 10(-5) mol/L of COD and 1.0 * 10(-4) mol/L of PAR were 6.1% and 8.7%, respectively. The limit of detection (LOD) values (S/N = 3) were 0.9 * 10(-8) mol/L and 1.0 * 10(-6) mol/L for COD and PAR, respectively. The proposed method was successfully applied to the determination of PAR and COD in commercial pharmaceutical formulations. Acceptable recoveries (90-110%) were obtained for the quantification of these drugs in the real samples. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26833977 TI - Corrigendum. PMID- 26833978 TI - Morphological Studies of Nucleologenesis in Giardia lamblia. AB - The nucleolus is a nuclear organelle involved in ribosome biogenesis. In most eukaryotes this structure disperses during prophase through anaphase and reorganizes at telophase by a process known as nucleologenesis. This process involves new transcription of ribosomal DNA at the nucleolar organizer region and the formation of prenucleolar bodies fusing to it. In Giardia lamblia, for a long time considered the only anucleolated eukaryote, a very small nucleolus has been recently described. In order to evaluate whether nucleologenesis is also present in Giardia, we analyzed the distribution of nucleolar material during telophase using different light and electron microscopy techniques including silver staining for the nucleolar organizer. Results indicate that in G. lamblia, nucleolar elements persist mainly as an intranuclear peripheral organelle during all stages of division, including telophase, however, no prenucleolar bodies are detected in the nucleoplasm. Therefore, in the parasite, nucleolar material is present throughout cell division including telophase and formation of prenucleolar bodies may not be required for nucleologenesis. PMID- 26833979 TI - Efficacy evaluation of D-dimer and modified criteria in overt and nonovert disseminated intravascular coagulation diagnosis. AB - INTRODUCTION: D-dimer (D-D) was shown to be an important indicator for the diagnosis of overt disseminated intravascular coagulation (DIC) and nonovert DIC. However, its diagnostic cutoff value in the clinic is not clearly defined. METHODS: D-D, fibrinogen degradation products (FDP), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fg), thrombin time (TT), antithrombin (AT), and blood platelet count (PLT) of 360 cases were used to assess the diagnostic efficacy of D-D (InnovanceR reagent) for the diagnosis of DIC and nonovert DIC, compared to, or combined with, other DIC coagulation indicators. RESULTS: When D-D > 3.0 MUg/mL was used as the cutoff, the sum of diagnostic sensitivity and specificity reached maximum values for DIC and nonovert DIC, whereas the sum of misdiagnoses and missed diagnosis rate was minimal. Excluding D-D, AT, or Fg, but not TT, from the test combination reduced the diagnostic sensitivity of DIC or nonovert DIC by various degrees. The area under the receiver-operating characteristic curve of D-D for diagnosing DIC and nonovert DIC was 0.97 and 0.98, respectively. Combining two factors, D-D > 3.0 MUg/mL and FDP > 10 mg/L, increased the sensitivity and specificity for the diagnosis of DIC and nonovert DIC. CONCLUSION: The cutoff value of D-D is >3.0 MUg/mL; combined testing of D-D and FDP could be used as primary screening for diagnosing DIC and nonovert DIC in clinical practice. PMID- 26833981 TI - Corrigendum: BACE1 RNA interference improves spatial memory and attenuates Abeta burden in a streptozotocin-induced tau hyperphosphorylated rat model. PMID- 26833980 TI - Cyclophilin A as a downstream effector of PI3K/Akt signalling pathway in multiple myeloma cells. AB - Cyclophilin A (Cyp A), a member of the peptidyl-prolyl isomerase (PPI) family, may function as a molecular signalling switch. Comparative proteomic studies have identified Cyp A as a potential downstream target of protein kinase B (Akt). This study confirmed that Cyp A is a downstream effector of the phosphatidylinositide 3-kinase (PI3K)/Akt signalling pathway. Cyp A was highly phosphorylated in response to interleukin-6 treatment, which was consistent with the accumulation of phosphorylated Akt, suggesting that Cyp A is a phosphorylation target of Akt and downstream effector of the PI3K/Akt pathway. Cyclosporine A (CsA), a PPI inhibitor, inhibited the growth of multiple myeloma (MM) U266 cells. Moreover, CsA treatment inhibited the activation of the signal transducer and activator of transcription 3 (STAT3) in MM U266 cells. Several Cyp A mutants were generated. Mutants with mutated AKT phosphorylation sites increased the G1 phase arrest in MM U266 cells. The other mutants that mimicked the phosphorylated state of Cyp A decreased the percentage of G1 phase. These results demonstrated that the states of phosphorylation of Cyp A by Akt can influence the progress of the cell cycle in MM U266 cells and that this effect is probably mediated through the Janus activated kinase 2/STAT3 signalling pathway. PMID- 26833983 TI - Cerebral Cortex Involvement in Neuromyelitis Optica Spectrum Disorder. AB - BACKGROUND AND PURPOSE: Brain lesions involving the cerebral cortex are rarely described in patients with neuromyelitis optica spectrum disorder (NMOSD), in contrast to multiple sclerosis. We investigated cerebral cortex involvement using conventional brain magnetic resonance imaging (MRI) in anti-aquaporin-4 (AQP4) antibody-positive NMOSD patients. METHODS: The study enrolled 215 NMOSD patients who were seropositive for the anti-AQP4 antibody from 5 referral hospitals, and retrospectively analyzed their demographic, clinical, and MRI findings. Abnormal cerebral cortex lesions on brain MRI were identified by a neuroradiologist and two neurologists using consensus. RESULTS: Most of the 215 enrolled patients (87%) were female. The median age at onset was 22.5 years (range: 15-36 years) and the mean follow-up duration was 123 months. Brain lesions were found in 143 of 194 patients (74%) in whom MRI was performed during follow-up. Brain lesions involving the cerebral cortex were identified in 6 of these 194 patients (3.1%). Five of the patients were female, and the six patients together had a median age of 29 years (range: 15-36 years) at the time of lesion presentation. Three of them showed leptomeningeal enhancement in the lesions. At presentation of the cortex-involving lesions, five of these patients were not being treated at the time of presentation, while the sixth was being treated with interferon-beta. CONCLUSIONS: Although rare, cortical involvement occurs in NMOSD and is commonly combined with leptomeningeal enhancement. We speculate that this occurs only in patients who are not treated appropriately with immunosuppressant drugs. PMID- 26833982 TI - Recombinant human thyrotropin-stimulated thyroglobulin level at the time of radioactive iodine ablation is an independent prognostic marker of differentiated thyroid carcinoma in the setting of prophylactic central neck dissection. AB - OBJECTIVE: We investigated the value of the stimulated thyroglobulin (Tg) level at the time of recombinant human thyrotropin (rhTSH)-aided remnant ablation for predicting disease status 1 year later in patients with DTC who underwent total thyroidectomy with central neck dissection (CND). DESIGN, SETTING, AND PARTICIPANT: This was a prospective observational study of 253 consecutive patients with DTC who underwent rhTSH-aided RAI ablation after total thyroidectomy and prophylactic CND. Patients with evidence of initial distant metastasis or positive Tg antibodies were excluded. MAJOR OUTCOME MEASURE: We compared rhTSH-stimulated Tg level at RAI ablation according to the disease status at 1 year and evaluated optimal cut-off value of rhTSH-stimulated Tg. Binary logistic regression analysis was performed to investigate the independent predictive factors for disease status 1 year after ablation. RESULTS: Among study participants, 228 (90.1%) were considered disease free at 1 year after remnant ablation. Patients with persistent or recurrent disease were more likely to be aged >=45 years, and to have N1b stage, TNM stage III or IV, and higher rhTSH stimulated Tg level at RAI ablation. The optimal cut-off of rhTSH-stimulated Tg for predicting persistent or recurrent disease was 1.79 ng/ml, with a negative predictive value of 99.5%. A serum rhTSH-stimulated Tg level >=1.79 at the time of ablation was independently associated with persistent or recurrent disease 1 year later. N1b stage tended to be associated with persistent or recurrent disease. CONCLUSION: A low stimulated serum Tg level at rhTSH-aided RAI ablation may be a favourable prognostic marker in the setting of prophylactic CND. PMID- 26833984 TI - Blood Pressure in Acute Ischemic Stroke. AB - Hypertension is present in up to 84% of patients presenting with acute stroke, and a smaller proportion of patients have blood pressures that are below typical values in the context of cerebral ischemia. Outcomes are generally worse in those who present with either low or severely elevated blood pressure. Several studies have provided valuable information about malignant trends in blood pressure during the transition from the acute to the subacute phase of stroke. It is not uncommon for practitioners in clinical practice to identify what appear to be pressure-dependent neurologic deficits. Despite physiologic and clinical data suggesting the importance of blood pressure modulation to support cerebral blood flow to ischemic tissue, randomized controlled trials have not yielded robust evidence for this in acute ischemic stroke. We highlight previous studies involving acute-stroke patients that have defined trends in blood pressure and that have evaluated the safety and efficacy of blood-pressure modulation in acute ischemic stroke. This overview reports the current status of this topic from the perspective of a stroke neurologist and provides a framework for future research. PMID- 26833985 TI - Prognostic Value of Initial Standard EEG and MRI in Patients with Herpes Simplex Encephalitis. AB - BACKGROUND AND PURPOSE: Herpes simplex encephalitis (HSE) is the most common type of sporadic encephalitis worldwide, and it remains fatal even when optimal antiviral therapy is applied. There is only a weak consensus on the clinical outcomes and prognostic factors in patients with HSE. This study examined whether the radiological and electrophysiological findings have a prognostic value in patients with HSE. METHODS: We retrospectively analyzed patients who were diagnosed with HSE by applying the polymerase chain reaction to cerebrospinal fluid and who received intravenous acyclovir at our hospital from 2000 to 2014. We evaluated the clinical outcomes at 6 months after onset and their correlations with initial and clinical findings, including the volume of lesions on MRI, the severity of EEG findings, and the presence of epileptic seizures at the initial presentation. RESULTS: Twenty-nine patients were enrolled (18 men and 11 women). Univariate analysis revealed that the presence of severe EEG abnormality and epileptic seizures at the initial presentation were significant correlated with a poor clinical outcome at 6 months (p=0.005 and p=0.009, respectively). In multivariate analysis, the presence of severe EEG abnormality was the only independent predictor of a poor outcome at 6 months (p=0.006). CONCLUSIONS: In cases of HSE, the initial EEG severity and seizure presentation may be useful predictive factors for the outcome at 6 months after acyclovir treatment. PMID- 26833988 TI - Posttraumatic Acute Disseminated Encephalomyelitis in a Child Resolved by Steroid Therapy: Case Report. PMID- 26833987 TI - Considerations When Subtyping Ischemic Stroke in Asian Patients. AB - Both the incidence and prevalence of stroke in Asia are steadily increasing, and the burden of stroke is particularly high in Asian countries. Although strokes in Asians and Caucasians share many common features, there are some differences that are probably due to differences in lifestyle and genetic background. While there have been advances in the stroke classification system, the assignment of Asian stroke patients to etiological categories has received little attention. The current classification system may not be well suited to Asian patients with ischemic stroke because the proportions and relative importance of stroke subtypes may differ with race and ethnicity. This review addresses concerns about the use of the current stroke classification system in Asian patients with ischemic stroke, and proposes a classification system that is more specific to the Asian population, in conjunction with discussing advances in diagnostic techniques. PMID- 26833986 TI - Habitual Sleep Duration, Unmet Sleep Need, and Excessive Daytime Sleepiness in Korean Adults. AB - BACKGROUND AND PURPOSE: Sleep need differs between individuals, and so the same duration of sleep will lead to sleep insufficiency in some individuals but not others. The aim of this study was to determine the separate and combined associations of both sleep duration and unmet sleep need with excessive daytime sleepiness (EDS) in Korean adults. METHODS: The participants comprised 2,769 Korean adults aged 19 years or older. They completed questionnaires about their sleep habits over the previous month. The question regarding sleep need was "How much sleep do you need to be at your best during the day?" Unmet sleep need was calculated as sleep need minus habitual sleep duration. Participants with a score of >10 on the Epworth Sleepiness Scale were considered to have EDS. RESULTS: The overall prevalence of EDS was 11.9%. Approximately one-third of the participants (31.9%) reported not getting at least 7 hours of sleep. An unmet sleep need of >0 hours was present in 30.2% of the participants. An adjusted multivariate logistic regression analysis revealed a significant excess risk of EDS in the groups with unmet sleep needs of >=2 hours [odds ratio (OR), 1.80; 95% confidence interval (CI), 1.27-2.54] and 0.01-2 hours (OR, 1.42; 95% CI, 1.02-1.98). However, habitual sleep duration was not significantly related to EDS. CONCLUSIONS: EDS was found to be associated with unmet sleep need but not with habitual sleep duration when both factors were examined together. We suggest that individual unmet sleep need is more important than habitual sleep duration in terms of the relation to EDS. PMID- 26833989 TI - Design and Synthesis of Novel Chiral Dirhodium(II) Carboxylate Complexes for Asymmetric Cyclopropanation Reactions. AB - A novel approach to the design of dirhodium(II) tetracarboxylates derived from (S)-amino acid ligands is reported. The approach is founded on tailoring the steric influences of the overall catalyst structure by reducing the local symmetry of the ligand's N-heterocyclic tether. The application of the new approach has led to the uncovering of [Rh2 (S-tert PTTL)4 ] as a new member of the dirhodium(II) family with extraordinary selectivity in cyclopropanation reactions. The stereoselectivity of [Rh2 (S-tert PTTL)4 ] was found to be comparable to that of [Rh2 (S-PTAD)4 ] (up to >99 % ee), with the extra benefit of being more synthetically accessible. Correlations based on X-ray structures to justify the observed enantioinduction are also discussed. PMID- 26833990 TI - Clinical and pathologic features of Aicardi-Goutieres syndrome due to an IFIH1 mutation: A pediatric case report. AB - We describe the case of a young patient with calcifying encephalopathy, born to asymptomatic parents. An extensive hypothesis-driven etiological assessment was performed and failed to detect the precise etiology during many years. We therefore decided to perform whole exome sequencing of the child-unaffected parents trio. A de novo pathogenic variant in the IFIH1 gene which has recently been shown to cause autosomal dominant forms of Aicardi-Goutieres syndrome was identified. This child presented with a severe form with neonatal thrombocytopenia and hepatomegaly, the latter having been detected during late gestation. Although first milestones were uneventful, he progressively lost motor skills from the age of 12 months and developed severe spastic paraplegia. Brain imaging revealed white matter abnormalities and extensive calcifications. He also presented atypical skin lesions, different from chilblains. His medical history was marked by two episodes of acute pancreatitis. We provide herein the results of pathological examination including detailed description of the neuropathological hallmarks. To our knowledge, this the first detailed clinico pathological description of a patient with an IFIH1 pathogenic variant. PMID- 26833991 TI - Nurse administrators' intentions and considerations in recruiting inactive nurses. AB - AIMS: To understand nurse administrators' intentions and considerations in recruiting inactive nurses and to examine predictors of intent to recruit. BACKGROUND: Few studies have provided insight into employer intentions and considerations in recruiting inactive nurses. METHODS: A census survey collected data from 392 nurse administrators via a mailing method. RESULTS: Overall, 89.0% of nurse administrators were willing to recruit inactive nurses. Stepwise regression analysis revealed that the only predictor of nurse administrators' intention to recruit was nurse turnover rate at the hospital. Nurse administrators perceived the most important recruiting considerations were inactive nurses' cooperation with alternating shifts, health status and nursing licence. The most frequent reasons for not recruiting were an inactive nurse's lack of understanding of the medical environment and poor nursing competence. CONCLUSIONS: Most hospital nurse administrators were willing to recruit inactive nurses. Inactive nurses who wish to return to work should be qualified, willing to work both day and night shifts, and in good health. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse administrators can reduce the nursing shortage by recruiting inactive nurses. Re-entry preparation programmes should be implemented that will provide inactive nurses with knowledge of the current medical environment and the skills required to improve their nursing competence. PMID- 26833992 TI - One-Shot Immunomodulatory Nanodiamond Agents for Cancer Immunotherapy. AB - The use of functional nanodiamonds (fNDs) to deliver CpG oligonucleotides (ODNs) for sustained immunostimulation is reported. It is demonstrated that monotherapy using this immunostimulatory agent significantly suppresses the tumor growth in two murine tumor models. This fND-based nanoagent opens new opportunities for immunotherapy, as well as clinical applications of various types of therapeutic nucleic acids. PMID- 26833993 TI - Supplementation of culture media with vitamin E improves mouse antral follicle maturation and embryo development from vitrified ovarian tissue. AB - AIM: The aim of this study was to evaluate the effects of preventive vitamin E (alpha-tocopherol) on antral follicle development and embryogenesis of oocytes obtained after vitrification of mouse ovarian tissue. METHODS: Female Balb/c mice were killed by cervical dislocation after the injection of pregnant mare's serum gonadotrophin (10 IU) and their ovaries were randomly divided into three groups: control or non-vitrified (n = 10), vitrification 1 (5, 10% ethylene glycol + 5, 10% dimethylsulfoxide) (n = 15), and vitrification 2 (10, 15% ethylene glycol + 10, 15% dimethylsulfoxide) (n = 15) with ascending concentration of cryoprotectants. After toxicity tests and vitrification-warming, mechanically isolated antral follicles were cultured in alpha-minimum essential medium, which was supplemented with or without alpha-tocopherol (100 MUM). The follicular maturation rates and embryo development were collected and assessed. Also, the viability, morphology and ultrastructure of derived antral follicles from vitrified ovaries were analyzed. RESULTS: The morphology and ultrastructure of follicles were well preserved in the vitrified groups and alpha-tocopherol supplementation of culture media significantly increased the proportion of oocytes that reached metaphase II blastocyst rates compared to non-alpha tocopherol supplemented media (P < 0.01). CONCLUSION: Vitamin E improves in vitro maturation rates and blastocyst rates of oocytes that are isolated from vitrified ovarian tissue. PMID- 26833994 TI - Clinical effects of midazolam or lidocaine co-induction with a propofol target controlled infusion (TCI) in dogs. AB - OBJECTIVE: To evaluate the propofol requirement, cardiovascular and respiratory variables using midazolam or lidocaine with a propofol target-controlled infusion (PTCI) for induction of anaesthesia in healthy dogs. STUDY DESIGN: Prospective, randomized, controlled blinded clinical trial. ANIMALS: Sixty client-owned dogs [American Society of Anesthesiologists (ASA) I-II] undergoing surgical procedures. METHODS: Thirty minutes after premedication with acepromazine (0.03 mg kg(-1) ) and morphine (0.2 mg kg(-1) ), PTCI was started and maintained at a plasma target concentration of 1 MUg mL(-1) . Three minutes later, dogs (n = 20 per group) received either 5 mL 0.9% sodium chloride (SG), 2 mg kg(-1) of lidocaine (LG) or 0.2 mg kg(-1) of midazolam (MG) intravenously (IV) as a co induction agent. Two minutes later, suitability for endotracheal intubation was assessed. If intubation was not possible, the propofol target was increased by 0.5 MUg mL(-1) every 60 seconds until it was successfully achieved. Heart rate (HR), respiratory rate (fR ), and oscillometric systolic arterial pressure (SAP), mean arterial pressure (MAP) and diastolic arterial pressure (DAP) were recorded immediately prior to commencing PTCI (B0), prior to intubation (BI), immediately after (T0), and at 3 (T3) and 5 (T5) minutes post-intubation. End-tidal partial pressures of carbon dioxide (PE(') CO2 ) were recorded at T0, T3 and T5. The occurrence of excitement at any time point was noted. RESULTS: The median (range) propofol target concentration for endotracheal intubation was significantly lower in MG, 1.5 (1.0-4.0) MUg mL(-1) compared with LG, 2.5 (1.5-4.5) MUg mL(-1) or SG, 3.0 (2.0-5.0) MUg mL(-1) . Heart rate, MAP, fR and PE(') CO2 were similar in the three groups at all time points. No excitement was reported in any dog. CONCLUSIONS AND CLINICAL RELEVANCE: Midazolam, but not lidocaine, provided a significant reduction in PTCI requirement for induction of anaesthesia thereby allowing successful intubation. However, cardiovascular and respiratory effects were not different between the groups. PMID- 26833995 TI - Aquagenic wrinkling: the importance to be known. PMID- 26833996 TI - Analysis of lignans in Magnoliae Flos by turbulent flow chromatography with online solid-phase extraction and high-performance liquid chromatography with tandem mass spectrometry. AB - In this study, a method coupling turbulent flow chromatography with online solid phase extraction and high-performance liquid chromatography with tandem mass spectrometry was developed for analyzing the lignans in Magnoliae Flos. By the online pretreatment of turbulent flow chromatography solid-phase extraction, the impurities removal and analytes concentration were automatically processed, and the lignans were separated rapidly and well. Seven lignans of Magnoliae Flos including epieudesmin, magnolin, 1-irioresinol-B-dimethyl ether, epi-magnolin, fargesin aschantin, and demethoxyaschantin were identified by comparing their retention behavior, UV spectra, and mass spectra with those of reference substances or literature data. The developed method was validated, and the good results showed that the method was not only automatic and rapid, but also accurate and reliable. The turbulent flow chromatography with online solid-phase extraction and high-performance liquid chromatography with tandem mass spectrometry method holds a high potential to become an effective method for the quality control of lignans in Magnoliae Flos and a useful tool for the analysis of other complex mixtures. PMID- 26833997 TI - Comparative study of quality of life and psychosocial characteristics in patients with psoriasis and leg ulcers. AB - Psoriasis and leg ulcers have a marked impact on the patient's quality of life and represent a life-long burden for affected patients. The aim of this study is to compare the quality of life, anxiety and depression, self-esteem, and loneliness in patients with psoriasis and leg-ulcer patients. Eighty patients with leg ulcers, eighty patients with psoriasis, and eighty healthy controls were included in this study. The quality of life, depression and anxiety, loneliness of the patient, and self-esteem were assessed using the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), the UCLA loneliness Scale (UCLA-Version 3), and the Rosenberg's Self-esteem Scale (RSES), respectively. The DLQI score among patients with psoriasis was 12.74 +/- 4.89 and leg ulcer patients was 13.28 +/- 2.57. The patients with psoriasis presented statistically significant higher anxiety (9.87 +/- 4.56) than both leg ulcer patients (8.26 +/- 2.82) and controls (6.45 +/- 1.89), while leg ulcer patients also presented higher anxiety than controls. Regarding self-esteem, although there were no significant differences between the patients with psoriasis (15.25 +/- 3.20) and the ones with leg ulcers (15.89 +/- 2.93), they both presented statistically significant lower self-esteem scores than control group (18.53 +/- 3.04). The patients with psoriasis presented statistically significant higher levels of loneliness and social isolation (46.18 +/- 6.63) compared to leg ulcer patients (43.73 +/- 5.68) than controls (42.49 +/- 3.41). Psoriasis and leg ulcers are long-term skin diseases associated with significant impairment of the patient's quality of life, anxiety, and self-esteem, which are frequently under recognized. PMID- 26833999 TI - Associations between serum lipid levels and depressive symptom in a Korean older population. PMID- 26833998 TI - A survey of US and Canadian hospitals' paediatric massive transfusion protocol policies. AB - BACKGROUND: Trauma is the leading cause of death in children >1 year of age, with haemorrhage as the most common cause of medically preventable deaths. While massive transfusion protocols (MTPs) have been investigated and used in adults to reduce death from haemorrhage, there are a paucity of published data on MTP practices and outcomes in children. This study aimed to survey current MTP policies and the frequency of activation at paediatric care centres. STUDY DESIGN AND METHODS: We conducted a survey of MTPs at hospitals in the United States and Canada, including children's general hospitals, children's specialty hospitals and children's units in general hospitals. We collected information on how the MTP is activated, what therapeutics are given, frequency of its use, and how it is audited for compliance. RESULTS: Forty-six survey responses were analysed. Physician discretion was the most common activation criteria (89%). A majority of sites (78%) targeted a 'high' (>=1 : 2) ratio of plasma to red blood cells (RBC). Fifteen percent of sites use antifibrinolytics in their MTPs. Eighty nine percent of sites have type-O RBC units and 48% of sites had thawed plasma units stored in an immediately available location. CONCLUSION: There is a wide variation in MTPs among paediatric hospitals with regard to both activation criteria and products administered. This underscores the need for future prospective studies to determine the most effective resuscitation methods for paediatric populations to improve outcomes and therapeutic safety for massive bleeding. PMID- 26834000 TI - Effect of simulation on knowledge, self-confidence, and skill performance in the USA: A quasi-experimental study. AB - In health care, high-fidelity simulation has been shown to result in increased student learning outcomes when compared to low-fidelity simulation. With educational facilities investing significant amounts of money into purchasing high-fidelity simulators, it is imperative to identify if the midlevel simulator, which is less costly, will result in the same learning outcomes. In this study, we examined the effect of midlevel-fidelity simulation versus low-fidelity simulation on Bachelor of Science in Nursing nursing students' knowledge, self confidence, and skill performance. A quasi-experimental design examined the effects of midlevel-fidelity simulation (n = 37) versus low-fidelity simulation (case study) (n = 37) in junior-level nursing students. There was a significant difference for both groups in knowledge and skill performance (measured with a mini Objective Structured Clinical Examination), but not between the groups. Unexpectedly, the case-study group had a higher level of self-confidence (self reported). The results of this study indicate that further research is needed to support faculties' selection of learning strategies with the lowest cost and highest effectiveness in achieving the desired learning outcomes. PMID- 26834001 TI - Inter-station intensity standardization for whole-body MR data. AB - PURPOSE: To develop and validate a method for performing inter-station intensity standardization in multispectral whole-body MR data. METHODS: Different approaches for mapping the intensity of each acquired image stack into the reference intensity space were developed and validated. The registration strategies included: "direct" registration to the reference station (Strategy 1), "progressive" registration to the neighboring stations without (Strategy 2), and with (Strategy 3) using information from the overlap regions of the neighboring stations. For Strategy 3, two regularized modifications were proposed and validated. All methods were tested on two multispectral whole-body MR data sets: a multiple myeloma patients data set (48 subjects) and a whole-body MR angiography data set (33 subjects). RESULTS: For both data sets, all strategies showed significant improvement of intensity homogeneity with respect to vast majority of the validation measures (P < 0.005). Strategy 1 exhibited the best performance, closely followed by Strategy 2. Strategy 3 and its modifications were performing worse, in majority of the cases significantly (P < 0.05). CONCLUSIONS: We propose several strategies for performing inter-station intensity standardization in multispectral whole-body MR data. All the strategies were successfully applied to two types of whole-body MR data, and the "direct" registration strategy was concluded to perform the best. Magn Reson Med 77:422 433, 2017. (c) 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. PMID- 26834002 TI - Nitrogen and Phosphorous Co-Doped Graphene Monolith for Supercapacitors. AB - The co-doping of heteroatoms has been regarded as a promising approach to improve the energy-storage performance of graphene-based materials because of the synergetic effect of the heteroatom dopants. In this work, a single precursor melamine phosphate was used for the first time to synthesise nitrogen/phosphorus co-doped graphene (N/P-G) monoliths by a facile hydrothermal method. The nitrogen contents of 4.27-6.58 at% and phosphorus levels of 1.03-3.00 at% could be controlled by tuning the mass ratio of melamine phosphate to graphene oxide in the precursors. The N/P-G monoliths exhibited excellent electrochemical performances as electrodes for supercapacitors with a high specific capacitance of 183 F g(-1) at a current density of 0.05 A g(-1), good rate performance and excellent cycling performance. Additionally, the N/P-G electrode was stable at 1.6 V in 1 m H2 SO4 aqueous electrolyte and delivered a high energy density of 11.33 Wh kg(-1) at 1.6 V. PMID- 26834003 TI - Synthesis of Nitrogen-Containing Rubicene and Tetrabenzopentacene Derivatives. AB - Carbon-based materials, such as acenes, fullerenes, and graphene nanoribbons, are viewed as the potential successors to silicon in the next generation of electronics. Although a number of methodologies provide access to these materials' all-carbon variants, relatively fewer strategies readily furnish their nitrogen-doped analogues. Herein, we report the rational design, preparation, and characterization of nitrogen-containing rubicenes and tetrabenzopentacenes, which can be viewed either as acene derivatives or as molecular fragments of fullerenes and graphene nanoribbons. The reported findings may prove valuable for the development of electron transporting organic semiconductors and for the eventual construction of larger carbonaceous systems. PMID- 26834004 TI - The Performance of Titanium-Zirconium Implants in the Elderly: A Biomechanical Comparative Study in the Minipig. AB - OBJECTIVES: The aim of this study was to test the following hypothesis: (1) Aging would adversely affect bone integration of implants; (2) Titanium-zirconium SLActive (TiZr-SLActive) implant might perform better in osseointegration than Ti SLA implant in aged group. MATERIALS AND METHODS: Thirteen miniature pigs (six of them were young adult minipigs, with other seven being aged ones.) were enrolled in this study. The right mandibular premolars (P1, P2, P3) and the first molar (M1) were extracted in all animals. Three months later, one TiZr-SLActive and one Ti-SLA implants were inserted into the endentulous area in mandible of each animal. The animals were sacrificed 8 weeks after placement of implants. Implants in the mandibles were used for removal torque (RT) tests, while vertebra and femur being retrieved for bone mineral density (BMD) tests. RESULTS: Implant success rate in the young group was significantly higher than that in the aged group. Higher survival rate of implants was also observed in younger group than that in the aged group but without significant difference. Within the young group, mean value for peak RT of Ti-SLA implants was higher than that of TiZr SLActive implants without significant difference. In the aged group, the TiZr SLActive implants showed a higher mean value for peak RT than Ti-SLA implants. No significant difference was found in the mean BMD in both vertebra and femur between different age groups. CONCLUSIONS: Within the limits of this study, aging could negatively affect osseointegration of dental implants. TiZr-SLActive implants might to some degree compensate for the compromise in osseointegration brought by aging. PMID- 26834005 TI - An Exploratory Study of the Knowledge of Personal Safety Skills Among Children with Developmental Disabilities and Their Parents. AB - BACKGROUND: This study assessed the knowledge of personal safety skills among children with developmental disabilities and their parents' perceptions of children's knowledge. METHOD: This exploratory study examined the mental health records of 37 children with developmental disabilities referred for an abuse risk reduction group in a community mental health setting. Qualitative analysis of children's responses to questions about personal safety skills (knowledge related to physical development and personal safety, an appropriate and inappropriate touch and safety skills to respond to an inappropriate touch) indicated participants' varied and inconsistent levels of knowledge. RESULTS: Consistent with the literature, the results indicate risk factors for sexual abuse among children with developmental disabilities, including children's difficulty distinguishing between an appropriate and inappropriate touch and the lack of knowledge regarding appropriate venues for disclosing an inappropriate touch. Among parents, a lack of certainty regarding their children's knowledge and the ability to keep themselves safe was identified. CONCLUSION: Results support the need for education about personal safety for children with developmental disabilities and their families. PMID- 26834006 TI - Evaluation of parameters obtained from the Sysmex XN-2000 for predicting the recovery of the absolute neutrophil count and platelets after hematopoietic stem cell transplantation. AB - INTRODUCTION: We analyzed abilities of parameters from Sysmex XN-2000 (Sysmex, Kobe, Japan) to predict absolute neutrophil count (ANC) and platelet recovery after hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. METHODS: We prospectively analyzed 911 follow-up peripheral blood samples from 44 HSCT-performed patients and evaluated the performances of the following parameters: WBC, immature granulocyte (IG), hematopoietic stem and progenitor cells (HPC), immature reticulocyte fraction (IRF), immature platelet fraction (IPF), platelet distribution width (PDW), mean platelet volume (MPV), and platelet larger cell ratio (P-LCR). RESULTS: When compared to four other parameters, the identification of initiation in IG (%)/HPC (%) increase enabled earlier prediction of ANC recovery to >500/MUL and >1000/MUL with more time benefit of 3.5-6.5 days/2.0-5.0 days and 3.0-6.0 days/2.0-5.0 days, respectively. When compared to IPF (%), the identification of initiation in PDW, MPV, and P-LCR (%) increase enabled earlier prediction of platelet recovery to >20 000/MUL and >50 000/MUL with more time benefit of 2.5-3.5 days and 2.0-3.0 days, respectively. However, the standard deviation of time benefit obtained from IG (%)/HPC (%)/PDW/MPV/P-LCR (%) was consistently large (3.0-4.3 days). CONCLUSIONS: There is a systematic pattern where a rise in most of the studied parameters can be observed in most patients before ANC/platelet recovery. However, the interindividual variation between the time of rise of these parameters and ANC/platelet recovery is large, and therefore, using these parameters to predict recovery in the individual patient is probably not meaningful in the clinical setting. PMID- 26834007 TI - Interactions between Streptococcus oralis, Actinomyces oris, and Candida albicans in the development of multispecies oral microbial biofilms on salivary pellicle. AB - The fungus Candida albicans is carried orally and causes a range of superficial infections that may become systemic. Oral bacteria Actinomyces oris and Streptococcus oralis are abundant in early dental plaque and on oral mucosa. The aims of this study were to determine the mechanisms by which S. oralis and A. oris interact with each other and with C. albicans in biofilm development. Spatial distribution of microorganisms was visualized by confocal laser scanning microscopy of biofilms labeled by differential fluorescence or by fluorescence in situ hybridization (FISH). Actinomyces oris and S. oralis formed robust dual species biofilms, or three-species biofilms with C. albicans. The bacterial components tended to dominate the lower levels of the biofilms while C. albicans occupied the upper levels. Non-fimbriated A. oris was compromised in biofilm formation in the absence or presence of streptococci, but was incorporated into upper biofilm layers through binding to C. albicans. Biofilm growth and hyphal filament production by C. albicans was enhanced by S. oralis. It is suggested that the interkingdom biofilms are metabolically coordinated to house all three components, and this study demonstrates that adhesive interactions between them determine spatial distribution and biofilm architecture. The physical and chemical communication processes occurring in these communities potentially augment C. albicans persistence at multiple oral cavity sites. PMID- 26834008 TI - The anabolic action of intermittent parathyroid hormone on cortical bone depends partly on its ability to induce nitric oxide-mediated vasorelaxation in BALB/c mice. AB - There is strong evidence that vasodilatory nitric oxide (NO) donors have anabolic effects on bone in humans. Parathyroid hormone (PTH), the only osteoanabolic drug currently approved, is also a vasodilator. We investigated whether the NO synthase inhibitor L-NAME might alter the effect of PTH on bone by blocking its vasodilatory effect. BALB/c mice received 28 daily injections of PTH[1-34] (80 ug/kg/day) or L-NAME (30 mg/kg/day), alone or in combination. Hindlimb blood perfusion was measured by laser Doppler imaging. Bone architecture, turnover and mechanical properties in the femur were analysed respectively by micro-CT, histomorphometry and three-point bending. PTH increased hindlimb blood flow by >30% within 10 min of injection (P < 0.001). Co-treatment with L-NAME blocked the action of PTH on blood flow, whereas L-NAME alone had no effect. PTH treatment increased femoral cortical bone volume and formation rate by 20% and 110%, respectively (P < 0.001). PTH had no effect on trabecular bone volume in the femoral metaphysis although trabecular thickness and number were increased and decreased by 25%, respectively. Co-treatment with L-NAME restricted the PTH stimulated increase in cortical bone formation but had no clear-cut effects in trabecular bone. Co-treatment with L-NAME did not affect the mechanical strength in femurs induced by iPTH. These results suggest that NO-mediated vasorelaxation plays partly a role in the anabolic action of PTH on cortical bone. PMID- 26834009 TI - Predictors for papillary thyroid cancer persistence and recurrence: a retrospective analysis with a 10-year follow-up cohort study. AB - OBJECTIVE: We aimed to determine outcome predictors of papillary thyroid cancer (PTC) persistence and recurrence, separately. CONTEXT: The factors contributing to either persistence or recurrence of PTC are poorly defined, as both outcomes are usually evaluated together. DESIGN AND PATIENTS: In this 10-year follow-up cohort study, 190 PTC patients were evaluated (18-85 years old; registered from 1 January 1990 to31 December 1999 at a Brazilian Cancer Care referral Hospital). After initial surgery, we examined persistence (disease detected up to 1 year), recurrence (disease detected after 1 year) and PTC-free status (disease absence during follow-up). MEASUREMENTS: Outcome predictors were modelled using multinomial logit regression analysis. RESULTS: The univariate analysis showed that persistence and recurrence were significantly associated with lymph node metastasis (OR = 12.33; OR = 2.84, respectively), local aggressiveness (OR = 5.22; OR = 3.35) and extrathyroidal extension (OR = 5.07; OR = 7.11). Persistence was associated with male sex (OR = 3.49), age above 45 years old at diagnosis (OR = 1.03), macroscopic lymph node metastasis (OR = 5.85), local aggressiveness (OR = 5.22), each 1-cm tumour size increase (OR = 1.34), a cancer care referral hospital as the place of initial surgery (OR = 2.3), thyroidectomy or near total thyroidectomy(OR = 3.03) and neck dissection (OR = 3.19). Recurrence was associated with the time of radioactive iodine ((131) I) therapy (OR = 3.71). After data modelling, persistence was associated with macroscopic lymph node metastasis (OR = 6.17), 1-cm increases in tumour size (OR = 1.30) and thyroidectomy or near total thyroidectomy (OR = 3.82), while recurrence was associated with surgery at referral hospital (OR = 3.79). CONCLUSIONS: The best predictors of persistence were tumour size and macroscopic lymph node metastasis; when the initial surgery is of quality, the recurrence depends more on tumour's biology aspects. PMID- 26834011 TI - Tissue-specific expression, developmentally and spatially regulated alternative splicing, and protein subcellular localization of OsLpa rice. AB - The OsLpa1 gene (LOC_Os57400) was identified to be involved in phytic acid (PA) metabolism because its knockout and missense mutants reduce PA content in rice grain. However, little is known about the molecular characteristics of OsLpa rice and of its homologues in other plants. In the present study, the spatial pattern of OsLpa1 expression was revealed using OsLpa1 promoter::GUS transgenic plants (GUS: beta-glucuronidase); GUS histochemical assay showed that OsLpa1 was strongly expressed in stem, leaf, and root tissues, but in floral organ it is expressed mainly and strongly in filaments. In seeds, GUS staining was concentrated in the aleurone layers; a few blue spots were observed in the outer layers of embryo, but no staining was observed in the endosperm. Three OsLpa1 transcripts (OsLpa1.1, OsLpa1.2, OsLpa1.3) are produced due to alternative splicing; quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis revealed that the abundance of OsLpa1.3 was negligible compared with OsLpa1.1 and OsLpa all tissues. OsLpa1.2 is predominant in germinating seeds (about 5 times that of OsLpa1.1), but its abundance decreases quickly with the development of seedlings and plants, whereas the abundance of OsLpa1.1 rises and falls, reaching its highest level in 45-d-old plants, with abundance greater than that of OsLpa both leaves and roots. In seeds, the abundance of OsLpa1 continuously increases with seed growth, being 27.5 and 15 times greater in 28 DAF (day after flowering) seeds than in 7-DAF seeds for OsLpa1.1 and OsLpa1.2, respectively. Transient expression of chimeric genes with green fluorescence protein (GFP) in rice protoplasts demonstrated that all proteins encoded by the three OsLpa1 transcripts are localized to the chloroplast. PMID- 26834012 TI - Developing antibodies from cholinesterase derived from prokaryotic expression and testing their feasibility for detecting immunogen content in Daphnia magna. AB - To yield cholinesterase (ChE) from prokaryotic expression, the ChE gene that belongs to Daphnia magna was amplified by reverse transcription-polymerase chain reaction (RT-PCR) using forward primer 5'-CCCYGGNGCSAT GATGTG-3' and reverse primer 5'-GYAAGTTRGCCCAATATCT-3'. To express the gene, one sequence of the amplified DNA, which was able to encode a putative protein containing two conserved carboxylesterase domains, was connected to the prokaryotic expression vector PET-29a(+). The recombinant vector was transformed into Escherichia coil BL21 (DE3). Protein expression was induced by isopropy-D-thiogalactoside. The expressed ChE was used as an immunogen to immunize BALB/c mice. The obtained antibodies were tested for their specificity towards crude enzymes from species such as Alona milleri, Macrobrachium nipponense, Bombyx mori, Chironomus kiiensis, Apis mellifera, Eisenia foetida, Brachydanio rerio, and Xenopus laevis. Results indicated that the antibodies had specificity suitable for detecting ChE in Daphnia magna. A type of indirect and non-competitive enzyme-linked immunosorbent assay (IN-ELISA) was used to test the immunoreactive content of ChE (ChE-IR) in Daphina magna. The detection limit of the IN-ELISA was found to be 14.5 ng/ml at an antiserum dilution of 1:22 000. Results from tests on Daphnia magna exposed to sublethal concentrations of triazophos indicated a maximal induction of 57.2% in terms of ChE-IR on the second day after the animals were exposed to a concentration of 2.10 MUg/L triazophos. Testing on animals acclimatized to a temperature of 16 degrees C indicated that ChE-IR was induced by 16.9% compared with the ChE-IR content detected at 21 degrees C, and the rate of induction was 25.6% at 10 degrees C. The IN-ELISA was also used to test the stability of ChE-IR in collected samples. Repeated freezing and thawing had no influence on the outcome of the test. All these results suggest that the polyclonal antibodies developed against the recombinant ChE are as efficient as those developed against the native ChE in detecting ChE content in Daphnia magna. PMID- 26834010 TI - Strategies used for genetically modifying bacterial genome: site-directed mutagenesis, gene inactivation, and gene over-expression. AB - With the availability of the whole genome sequence of Escherichia coli or Corynebacterium glutamicum, strategies for directed DNA manipulation have developed rapidly. DNA manipulation plays an important role in understanding the function of genes and in constructing novel engineering bacteria according to requirement. DNA manipulation involves modifying the autologous genes and expressing the heterogenous genes. Two alternative approaches, using electroporation linear DNA or recombinant suicide plasmid, allow a wide variety of DNA manipulation. However, the over-expression of the desired gene is generally executed via plasmid-mediation. The current review summarizes the common strategies used for genetically modifying E. coli and C. glutamicum genomes, and discusses the technical problem of multi-layered DNA manipulation. Strategies for gene over-expression via integrating into genome are proposed. This review is intended to be an accessible introduction to DNA manipulation within the bacterial genome for novices and a source of the latest experimental information for experienced investigators. PMID- 26834013 TI - bmo-miR-0001 and bmo-miR-0015 down-regulate expression of Bombyx mori fibroin light chain gene in vitro. AB - Based on bioinformatic analysis, we selected two novel microRNAs (miRNAs), bmo miR-0001 and bmo-miR-0015, from high-throughput sequencing of the Bombyx mori larval posterior silk gland (PSG). Firstly, we examined the expression of bmo-miR 0001 and bmo-miR 12 different tissues of the 5th instar Day-3 larvae of the silkworm. The results showed that the expression levels of both bmo-miR-0001 and bmo-miR-0015 were obviously higher in the PSG than in other tissues, implying there is a spatio-temporal condition for bmo-miR-0001 and bmo-miR-0015 to regulate the expression of BmFib-L. To test this hypothesis, we constructed pri bmo-miR-0001 expressing the plasmid pcDNA3.0 and pri-bmo-miR-0015 expressing the plasmid pcDNA3.0 [ie1-egfp-pri-bmo-miR-0015-SV40]. Finally, the BmN cells were harvested and luciferase activity was detected. The results showed that luciferase activity was reduced significantly (P<0.05) in BmN cells co transfected by pcDNA3.0 [ie1-egfp-pri-bmo-miR-0001-SV40] or pcDNA3.0 with pGL3.0 [A3-luc-Fib-L-3'UTR-SV40], suggesting that both bmo-miR-0001 and bmo-miR-0015 can down-regulate the expression of BmFib-L in vitro. PMID- 26834014 TI - PGC-1alpha regulates the cell cycle through ATP and ROS in CH1 cells. AB - Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) is a transcriptional co-activator involved in mitochondrial biogenesis, respiratory capacity, and oxidative phosphorylation (OXPHOS). PGC-1alpha plays an important role in cellular metabolism and is associated with tumorigenesis, suggesting an involvement in cell cycle progression. However, the underlying mechanisms mediating its involvement in these processes remain unclear. To elucidate the signaling pathways involved in PGC-1alpha function, we established a cell line, CH1 PGC-1alpha, which stably overexpresses PGC-1alpha. Using this cell line, we found that over-expression of PGC-1alpha stimulated extra adenosine triphosphate (ATP) and reduced reactive oxygen species (ROS) production. These effects were accompanied by up-regulation of the cell cycle checkpoint regulators CyclinD1 and CyclinB1. We hypothesized that ATP and ROS function as cellular signals to regulate cyclins and control cell cycle progression. Indeed, we found that reduction of ATP levels down-regulated CyclinD1 but not CyclinB1, whereas elevation of ROS levels down-regulated CyclinB1 but not CyclinD1. Furthermore, both low ATP levels and elevated ROS levels inhibited cell growth, but PGC-1alpha was maintained at a constant level. Together, these results demonstrate that PGC 1alpha regulates cell cycle progression through modulation of CyclinD1 and CyclinB1 by ATP and ROS. These findings suggest that PGC-1alpha potentially coordinates energy metabolism together with the cell cycle. PMID- 26834015 TI - Immunomodulatory effect of a formula developed from American ginseng and Chinese jujube extracts in mice. AB - BACKGROUND: American ginseng (Panax quinquefolius L.) and Chinese jujube (Zizyphus jujuba Mill.) are commonly used in traditional Chinese medicine to enhance immune function. OBJECTIVE: The present study aimed to develop one Chinese prescription, Shenzao Cha (SZC), consisting of American ginseng and Chinese jujube, and systematically investigate its immunomodulation in healthy ICR mice. METHODS: Normal ICR mice received intragastric administration of SZC (1.3, 2.6, and 5.2 g raw material/kg body weight) once daily for four weeks, while a control group received the same amount of sterile water. RESULTS: SZC significantly increased the spleen and thymus indices and T-lymphocyte proliferation, while the T-lymphocyte proliferation in the 5.2 g/kg group was 1.4 fold higher than that in the control. Further, 1.3 g/kg SZC could markedly improve hemolytic activity by 25.2%, and 2.6 g/kg SZC increased the NK cell activity by 78.6% relative to the control. In addition, the activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase), that participated in modulating oxidative stress, were significantly increased in the liver, spleen, thymus, and serum, while the contents of malondialdehyde were dramatically decreased. CONCLUSIONS: SZC exhibited potent immunomodulatory effects on innate and adaptive immunity in healthy ICR mice, as well as potential antioxidant activity for prevention of oxidative stress, which was suggested to partly contribute to the immune enhancement. PMID- 26834017 TI - Generation of Aryl Radicals through Reduction of Hypervalent Iodine(III) Compounds with TEMPONa: Radical Alkene Oxyarylation. AB - A novel method for selective generation of aryl radicals from diaryliodonium salts and iodanylidene malonates with sodium 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPONa) as a single-electron transfer (SET) reducing reagent is described. In the presence of various alkenes, aryl radicals formed after SET-reduction of hypervalent iodine compounds undergo alkene addition and the adduct radicals that are thus generated are efficiently trapped by the concomitantly generated TEMPO radical to eventually afford oxyarylated products in moderate to very good yields. The efficiency of aryl radical generation of various iodine(III) reagents is studied and the generation of an iodanylidene malonate aryl radical is also investigated by computational methods. PMID- 26834016 TI - Potential natural exposure of endangered red-crowned crane (Grus japonensis) to mycotoxins aflatoxin B1, deoxynivalenol, zearalenone, T-2 toxin, and ochratoxin A. AB - A survey was conducted to determine whether mycotoxins were present in the foods consumed by red-crowned cranes (Grus japonensis) in the Yancheng Biosphere Reserve, China. Collected in the reserve's core, buffer, and experimental zones during overwintering periods of 2013 to 2015, a total of 113 food samples were analyzed for aflatoxin B1, deoxynivalenol, zearalenone, T-2 toxin, and ochratoxin A using high performance liquid chromatography (HPLC). The contamination incidences vary among different zones and the mycotoxins levels of different food samples also presented disparity. Average mycotoxin concentration from rice grain was greater than that from other food types. Among mycotoxin-positive samples, 59.3% were simultaneously contaminated with more than one toxin. This study demonstrated for the first time that red-crowned cranes were exposed to mycotoxins in the Yancheng Biosphere Reserve and suggested that artificial wetlands could not be considered good habitats for the birds in this reserve, especially rice fields. PMID- 26834018 TI - Novel 14q11.2 microduplication including the CHD8 and SUPT16H genes associated with developmental delay. AB - Neurodevelopmental disorders have long been associated with chromosomal abnormalities, including microdeletions and microduplications. Submicroscopic 14q11.2 deletions involving the CHD8 and SUPT16H genes have been reported in patients with developmental delay (DD)/intellectual disability (ID) or autism spectrum disorders (ASDs) and/or macrocephaly. Recently, disruptive CHD8 mutations were described in patients with similar phenotypes further showing pivotal role of CHD8 gene in the pathogenesis of DD/ID or ASDs. We report here the first case of ~445 kb de novo microduplication, encompassing the minimal critical 14q11.2 deletion region, in 8-year-old boy showing DD, cognitive impairment and facial dysmorphism. Our results suggest that gain of the chromosomal region 14q11.2 is causative for clinical findings present in the patient. PMID- 26834019 TI - Immunolocalization of the Anti-Mullerian Hormone (AMH) in Caprine Follicles and the Effects of AMH on In Vitro Culture of Caprine Pre-antral Follicles Enclosed in Ovarian Tissue. AB - The aims of this study were to evaluate the localization, by immunohistochemistry, of the anti-Mullerian hormone (AMH) in goat ovaries and to investigate its effects on the in vitro survival and development of caprine pre antral follicles enclosed in fragments of ovarian tissue. Pre-antral follicles were cultured in vitro for 1 or 7 days in alpha-MEM(+) in the absence or presence of kit ligand (KL; 50 ng/ml, positive control) or AMH (50 or 150 ng/ml). The results showed that AMH was localized in oocytes and granulosa cells from the primordial follicle to antral follicle stages. Addition of AMH maintained the percentage of developing follicles, similar to that in the uncultured control; however, the percentage of developing follicles was significantly lower than that in the cultured control and KL. Nonetheless, addition of AMH to the culture medium did not affect survival rates and follicular growth. In conclusion, this study demonstrated that the expression of AMH varies according to the compartment and stage of follicular development. Furthermore, AMH inhibits the activation of caprine primordial follicles. PMID- 26834020 TI - Clueless is a conserved ribonucleoprotein that binds the ribosome at the mitochondrial outer membrane. AB - Mitochondrial function is tied to the nucleus, in that hundreds of proteins encoded by nuclear genes must be imported into mitochondria. While post translational import is fairly well understood, emerging evidence supports that mitochondrial site-specific import, or co-translational import, also occurs. However, the mechanism and the extent to which it is used are not fully understood. We have previously shown Clueless (Clu), a conserved multi-domain protein, associates with mitochondrial outer membrane proteins, including Translocase of outer membrane 20, and genetically and physically interacts with the PINK1-Parkin pathway. The human ortholog of Clu, Cluh, was shown to bind nuclear-encoded mitochondrially destined mRNAs. Here we identify the conserved tetratricopeptide domain of Clu as predominantly responsible for binding mRNA. In addition, we show Clu interacts with the ribosome at the mitochondrial outer membrane. Taken together, these data support a model whereby Clu binds to and mitochondrially targets mRNAs to facilitate mRNA localization to the outer mitochondrial membrane, potentially for site-specific or co-translational import. This role may link the presence of efficient mitochondrial protein import to mitochondrial quality control through the PINK1-Parkin pathway. PMID- 26834021 TI - On the development of extragonadal and gonadal human germ cells. AB - Human germ cells originate in an extragonadal location and have to migrate to colonize the gonadal primordia at around seven weeks of gestation (W7, or five weeks post conception). Many germ cells are lost along the way and should enter apoptosis, but some escape and can give rise to extragonadal germ cell tumors. Due to the common somatic origin of gonads and adrenal cortex, we investigated whether ectopic germ cells were present in the human adrenals. Germ cells expressing DDX4 and/or POU5F1 were present in male and female human adrenals in the first and second trimester. However, in contrast to what has been described in mice, where 'adrenal' and 'ovarian' germ cells seem to enter meiosis in synchrony, we were unable to observe meiotic entry in human 'adrenal' germ cells until W22. By contrast, 'ovarian' germ cells at W22 showed a pronounced asynchronous meiotic entry. Interestingly, we observed that immature POU5F1+ germ cells in both first and second trimester ovaries still expressed the neural crest marker TUBB3, reminiscent of their migratory phase. Our findings highlight species-specific differences in early gametogenesis between mice and humans. We report the presence of a population of ectopic germ cells in the human adrenals during development. PMID- 26834023 TI - Expectant management of a case of uterine arteriovenous malformation with an ovarian artery aneurysm. AB - Uterine arteriovenous malformations are rare and their true prevalence is unknown. Selective arterial embolization is used as first-line therapy for acute severe vaginal hemorrhage associated with uterine arteriovenous malformations. However, some patients with no vaginal bleeding have been treated conservatively, so the optimal treatment modality for arteriovenous malformations is unclear. We describe a 58-year-old woman with uterine arteriovenous malformation and an ovarian artery aneurysm who was successfully treated with an expectant management approach along with an assessment of age, symptoms, and imaging findings. PMID- 26834022 TI - Co-expression of the protease furin in Nicotiana benthamiana leads to efficient processing of latent transforming growth factor-beta1 into a biologically active protein. AB - Transforming growth factor beta (TGF-beta) is a signalling molecule that plays a key role in developmental and immunological processes in mammals. Three TGF-beta isoforms exist in humans, and each isoform has unique therapeutic potential. Plants offer a platform for the production of recombinant proteins, which is cheap and easy to scale up and has a low risk of contamination with human pathogens. TGF-beta3 has been produced in plants before using a chloroplast expression system. However, this strategy requires chemical refolding to obtain a biologically active protein. In this study, we investigated the possibility to transiently express active human TGF-beta1 in Nicotiana benthamiana plants. We successfully expressed mature TGF-beta1 in the absence of the latency-associated peptide (LAP) using different strategies, but the obtained proteins were inactive. Upon expression of LAP-TGF-beta1, we were able to show that processing of the latent complex by a furin-like protease does not occur in planta. The use of a chitinase signal peptide enhanced the expression and secretion of LAP-TGF beta1, and co-expression of human furin enabled the proteolytic processing of latent TGF-beta1. Engineering the plant post-translational machinery by co expressing human furin also enhanced the accumulation of biologically active TGF beta1. This engineering step is quite remarkable, as furin requires multiple processing steps and correct localization within the secretory pathway to become active. Our data demonstrate that plants can be a suitable platform for the production of complex proteins that rely on specific proteolytic processing. PMID- 26834025 TI - Fear, Faith, Hope, and Courage. PMID- 26834024 TI - Cost-Effectiveness of Comprehensive, Integrated Care for First Episode Psychosis in the NIMH RAISE Early Treatment Program. AB - This study compares the cost-effectiveness of Navigate (NAV), a comprehensive, multidisciplinary, team-based treatment approach for first episode psychosis (FEP) and usual Community Care (CC) in a cluster randomization trial. Patients at 34 community treatment clinics were randomly assigned to either NAV (N = 223) or CC (N = 181) for 2 years. Effectiveness was measured as a one standard deviation change on the Quality of Life Scale (QLS-SD). Incremental cost effectiveness ratios were evaluated with bootstrap distributions. The Net Health Benefits Approach was used to evaluate the probability that the value of NAV benefits exceeded its costs relative to CC from the perspective of the health care system. The NAV group improved significantly more on the QLS and had higher outpatient mental health and antipsychotic medication costs. The incremental cost effectiveness ratio was $12 081/QLS-SD, with a .94 probability that NAV was more cost-effective than CC at $40 000/QLS-SD. When converted to monetized Quality Adjusted Life Years, NAV benefits exceeded costs, especially at future generic drug prices. PMID- 26834026 TI - Working Memory Deficit as a Risk Factor for Severe Apathy in Schizophrenia: A 1 Year Longitudinal Study. AB - Apathy, described as impaired motivation and goal-directed behavior, is a common yet often overlooked multidimensional psychopathological state in schizophrenia. Its underlying cognitive processes remain largely unexplored. Data was drawn from a longitudinal hospital study of patients with a DSM-IV diagnosis of schizophrenia; 137 (82.5%) participated at the 1-month follow-up and 81 (59.1%) at the 1-year follow-up. Apathy was assessed with the Lille Apathy Rating Scale, validated in French and in schizophrenia. Severe apathy, overall (total score > 13) and on 4 previously identified distinct dimensions, was considered. Episodic verbal learning was assessed with the California Verbal Learning Test, executive functioning with the Trail Making Test, the Six Element Test and the Stop Signal Paradigm and working memory with the Letter-Number Sequencing Test. After controlling for confounding variables, only episodic verbal learning was associated with severe overall apathy in the cross-sectional study. At 1 year, working memory was associated with an increased risk of severe overall apathy, adjusting for baseline apathy. Using a dimensional approach to apathy, specific types of cognition were found to be associated with specific dimensions of apathy. Our findings confirm the need for a multidimensional approach of negative symptoms in schizophrenia. Moreover, cognitive functioning could be a risk factor for developing severe apathy. Cognitive remediation may thus be a useful non pharmacological intervention for treating apathy in schizophrenia patients. PMID- 26834028 TI - Indirect enantioseparation of fluoxetine in mouse serum by derivatization with 1R (-)-menthyl chloroformate followed by ultra high performance liquid chromatography and quadrupole time-of-flight mass spectrometry. AB - Here we describe a simple and sensitive analytical method for the enantioselective quantification of fluoxetine in mouse serum using ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry. The sample preparation method included a simple deproteinization with acetonitrile in 50 MUL of serum, followed by derivatization of the extracts in 50 MUL of 2 mM 1R-(-)-menthyl chloroformate at 45oC for 55 min. These conditions were statistically optimized through response surface methodology using a central composite design. Under the optimized conditions, neither racemization nor kinetic resolution occurred. The derivatized diastereomers were readily resolved on a conventional sub-2 MUm C18 column under a simple gradient elution of aqueous methanol containing 0.1% formic acid. The established method was validated and found to be linear, precise, and accurate over the concentration range of 5.0-1000.0 ng/mL for both R and S enantiomers (r(2) > 0.993). Stability tests of the prepared samples at three different concentration levels showed that the R- and S-fluoxetine derivatives were relatively stable for 48 h. No significant matrix effects were observed. Last, the developed method was successfully used for enantiomeric analysis of real serum samples collected at a number of time points from mice administered with racemic fluoxetine. PMID- 26834029 TI - Recurrent Jarisch-Herxheimer reaction in late latent syphilis. PMID- 26834027 TI - Stress Sensitivity, Aberrant Salience, and Threat Anticipation in Early Psychosis: An Experience Sampling Study. AB - While contemporary models of psychosis have proposed a number of putative psychological mechanisms, how these impact on individuals to increase intensity of psychotic experiences in real life, outside the research laboratory, remains unclear. We aimed to investigate whether elevated stress sensitivity, experiences of aberrant novelty and salience, and enhanced anticipation of threat contribute to the development of psychotic experiences in daily life. We used the experience sampling method (ESM) to assess stress, negative affect, aberrant salience, threat anticipation, and psychotic experiences in 51 individuals with first episode psychosis (FEP), 46 individuals with an at-risk mental state (ARMS) for psychosis, and 53 controls with no personal or family history of psychosis. Linear mixed models were used to account for the multilevel structure of ESM data. In all 3 groups, elevated stress sensitivity, aberrant salience, and enhanced threat anticipation were associated with an increased intensity of psychotic experiences. However, elevated sensitivity to minor stressful events (chi(2)= 6.3,P= 0.044), activities (chi(2)= 6.7,P= 0.036), and areas (chi(2)= 9.4,P= 0.009) and enhanced threat anticipation (chi(2)= 9.3,P= 0.009) were associated with more intense psychotic experiences in FEP individuals than controls. Sensitivity to outsider status (chi(2)= 5.7,P= 0.058) and aberrantly salient experiences (chi(2)= 12.3,P= 0.002) were more strongly associated with psychotic experiences in ARMS individuals than controls. Our findings suggest that stress sensitivity, aberrant salience, and threat anticipation are important psychological processes in the development of psychotic experiences in daily life in the early stages of the disorder. PMID- 26834030 TI - Effects of tretinoin on wound healing in aged skin. AB - Aged and adult populations have differences in the structural, biological, and healing properties of skin. Comparative studies of healing under the influence of retinoids in both these populations are very important and, to the best of our knowledge, have not been performed to date. The purpose of this study was to compare the activities of topical tretinoin in aged and adult animal models of wound healing by secondary intention. Male aged rats (24 months old, n = 7) and adult rats (6 months old, n = 8) were used. The rats were assigned to the following groups according to the dates on which wound samples were excised (day 14 or 21 after model creation): treated group, control group, and naive group. Topical application of tretinoin cream was used only on the proximal wound and was applied daily for 7 days. Wound healing areas were measured using metal calipers, and morphological analysis was performed. Slides were stained with Hematoxylin and Eosin, Masson's trichrome, and periodic acid-Schiff stains. Statistical analysis adopted a 5% coefficient for rejection of the null hypothesis. Although aged animals showed skin repair, complete reepithelialization was found on day 21 in some animals of both groups (treated and control). In aged rats, the wound area was significantly smaller in treated wounds than in untreated wounds, resulting in a larger scar area compared with the adult group. When treated wounds were compared, no differences were found between the wound areas in adult and aged rats. As expected, the collagen concentration was higher in normal skin from adult rats than in normal skin from aged animals, but there was no difference when aged skin was treated with tretinoin. These results indicate that tretinoin increases collagen synthesis in aged skin and returns the healing process to a normal state of skin healing. PMID- 26834032 TI - Rotating Magnetocaloric Effect in an Anisotropic Molecular Dimer. AB - In contrast to the mainstream research on molecular refrigerants that seeks magnetically isotropic molecules, we show that the magnetic anisotropy of dysprosium acetate tetrahydrate, [{Dy(OAc)3 (H2 O)2}2]?4 H2O (1), can be efficiently used for cooling below liquid-helium temperature. This is attained by rotating aligned single-crystal samples in a constant applied magnetic field. The envisioned advantages are fast cooling cycles and potentially compact refrigerators. PMID- 26834031 TI - Transverse relaxation of selectively excited metabolites in stroke at 21.1 T. AB - PURPOSE: This study seeks to evaluate in vivo T2 relaxation times of selectively excited stroke-relevant metabolites via 1 H relaxation-enhanced magnetic resonance spectroscopy (RE-MRS) at 21.1 T (900 MHz). METHODS: A quadrature surface coil was designed and optimized for investigations of rodents at 21.1 T. With voxel localization, a RE-MRS pulse sequence incorporating the excitation of selected metabolites was modified to include a variable echo delay for T2 measurements. A middle cerebral artery occlusion (MCAO) animal model for stroke was examined with spectra taken 24 h post occlusion. Fourteen echo times were acquired, with each measurement completed in less than 2 min. RESULTS: The RE-MRS approach produced high-quality spectra of the selectively excited metabolites in the stroked and contralateral regions. T2 measurements reveal differential results between these regions, with significance achieved for lactic acid. CONCLUSION: Using the RE-MRS technique at ultra-high magnetic field and an optimized quadrature surface coil design, full metabolic T2 quantifications in a localized voxel is now possible in less than 27 min. Magn Reson Med 77:520-528, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26834033 TI - Dysphoria is a risk factor for depression in medically ill older people. AB - OBJECTIVES: Depression in older people is commonly under diagnosed and is associated with increased morbidity and mortality. Because older people currently occupy 65% of acute hospital beds, it is crucial for them to be properly assessed for depression to optimise their medical care. The aim of this study was to identify potential risk factors for depression in the medically ill in order to improve their inpatient care. METHODS: This was a 2-year observational study of consequent referrals to the Newcastle Liaison Team for Older Adults. Out of a total number of 1586 referred patients, 1197 were included in the final analysis of data. Information about their age, main medical history, cognitive impairment and use of antidepressants was collected. All subjects were screened for dementia, depression and delirium. Proportions were compared using the chi squared test. Clinical depression as a binary variable was modelled using logistic regression. RESULTS: Higher risk for depression was associated with pain (odds ratio (OR) = 1.76; p = 0.033) and a previous history of depression (OR = 2.22; p < 0.001). Cognitive impairment (OR = 0.44, p < 0.001) and delirium (OR = 0.49; p < 0.001) decreased the likelihood for having depression. Subjective feelings of emptiness, being unhappy and depressed alone (R2 = 37.4%) and cognitive impairment (R2 = 39.5%) were the best multivariable model to explain depression in medically ill people. CONCLUSION: Dysphoric mood results in depression in older people with medical health problems. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26834034 TI - Hydrogen from Water over Openly-Structured Graphitic Carbon Nitride Polymer through Photocatalysis. AB - Openly-structured g-C3 N4 microspheres (CNMS) are developed through a well controlled strategy. These materials have unique features of open 3 D structure, ordered hierarchical porosity, and improved optical and electronic properties. Hydrogen evolution from water is performed under a 300 W Xe lamp with a cut-off filter (lambda>420 nm) and Pt nanoparticles are used as the co-catalyst (3.0 wt%). The catalyst prepared at 600 degrees C (CNMS-600) has a hydrogen evolution rate (HER) of 392 MUmol h(-1) (apparent quantum yield, AQY=6.3%) at 420 nm. This value is higher than that of g-C3 N4 nanosheets prepared through thermal oxidation, liquid exfoliation, or chemical exfoliation. The HER value is only 27 MUmol h(-1) (AQY=0.43%) at 420 nm for bulk g-C3 N4 from melamine. The evolution of openly-structured CNMS was investigated by TEM, FTIR, and XRD. The improved optical and electronic properties were demonstrated through UV/Vis absorption spectra, valence-band X-ray photoelectron spectroscopy, photoluminescence spectroscopy, electron paramagnetic resonance spectroscopy, and electrochemical impedance spectroscopy. PMID- 26834035 TI - eLearning: the right tool for the job? PMID- 26834036 TI - 'Disability Means, um, Dysfunctioning People': A Qualitative Analysis of the Meaning and Experience of Disability among Adults with Intellectual Disabilities. AB - BACKGROUND: There has been little qualitative analysis of the experience of stigma, social comparisons and conception of identity among adults with intellectual disabilities (ID). This study aimed to develop an understanding of how adults with intellectual disabilities experience their own disability, and any implications relating to self-esteem, stigma and social interactions. MATERIALS AND METHODS: Fifteen adults with intellectual disabilities were interviewed using semi-structured, open-ended questions regarding disability, social interactions and self-esteem. Interviews were analysed independently by two researchers using interpretive phenomenological analysis. RESULTS: Three major themes emerged during analysis, exploring pressure on participants to behave in a socially normative way, tendency to produce personal definitions of disability and consistently limited knowledge of and discomfort around common disability terminology. CONCLUSIONS: Participants' clearly experienced feelings of difference, despite a lack of articulation. Limited understanding of both terminology and conceptualization of disability status could negatively impact self-esteem, person-centred actions and political movement. PMID- 26834037 TI - Prevalence of co-occurring alcohol and other drug use in an Australian older adult mental health service. AB - Co-occurring mental illness and substance use disorder, known as dual diagnosis, is a significant challenge to mental health services. Few older adult specific alcohol and other drug treatment services exist, meaning older adult mental health services may become the default treatment option for many. Evidence suggests that dual diagnosis leads to substandard treatment outcomes, including higher rates of psychiatric relapse, higher costs of care and poorer treatment engagement. This paper explores the prevalence of co-occurring alcohol and other drug (AOD) use in an older adult community mental health service in inner Melbourne, Australia. This aim was accomplished by using a retrospective file audit of clinical intake assessments (n = 593) performed on consumers presenting to the service over a two-year period, June 2012-2014. Of consumers presenting to the service, 15.5% (n = 92) were assessed by clinicians as having co-occurring AOD use. Depression predominated in the dual diagnosis group as the primary mental health disorder. Dual diagnosis consumers in this sample were statistically more likely to be male and younger than their non-dual diagnosis counterparts. A limitation of this audit was the lack of implementation of screening tools, leaving assessment to clinical judgement or the interest of the clinician. This may also explain the discrepancy between the results of this study and previous work. Although appearing to be a relatively small percentage of assessments, the results accounted for 92 individuals with complex mental health, AOD and medical issues. Poor screening procedures in a population that is traditionally difficult to assess need to be rectified to meet the future challenges inherent in the ageing baby boomer generation, changing drug use trends and extended lifespans through harm reduction initiatives and medical advancements. PMID- 26834038 TI - Gene and whole genome analyses reveal that the mycobacterial strain JS623 is not a member of the species Mycobacterium smegmatis. AB - Unexpected differences were found between the genome of strain JS623, used in bioremediation studies, and the genome of strain mc(2) 155, a model organism for investigating basic biology of mycobacteria. Both strains are currently assigned in the databases to the species Mycobacterium smegmatis and, consequently, the environmental isolate JS623 is increasingly included as a representative of that species in comparative genome-based approaches aiming at identifying distinctive traits of the different members of the genus Mycobacterium. We applied traditional molecular taxonomic procedures--inference of single and concatenated gene trees--to re-evaluate the membership of both strains to the same species, adopting the latest accepted cut-off values for species delimitation. Additionally, modern whole genome-based in silico methods where performed in a comprehensive molecular phylogenetic analysis of JS623 and other members of the genus Mycobacterium. These analyses showed that all relevant genome parameters of JS623 clearly separate this strain from M. smegmatis. The strain JS623 should be corrected as Mycobacterium sp. not only in the literature but, even more importantly, in the database entries, as inclusion of the genome wrongly attributed to the M. smegmatis species in comparative studies will result in misleading conclusions. PMID- 26834039 TI - The association between airline flight and sinonasal symptoms. AB - BACKGROUND: Airplane cabin supply air has been shown to contain multiple possible respiratory irritants. In addition, changes in barometric pressure in flight may contribute to specific respiratory conditions. Therefore, there may be an association between commercial airline flight and sinus disease. METHODS: Participants of the Secondhand-Smoke, Air Quality and Respiratory Health Among Flight Attendants Study were administered an online questionnaire pertaining to their flight experience and respiratory health. Working years, working days per month, and number of trips per month were quantified, as well as smoking exposure and self-reported physician diagnoses of sinusitis, asthma, and rhinitis. The sinonasal outcomes were quantified using a Respiratory Questionnaire Survey (RQS) score. Multivariable analyses were performed to evaluate the associations between flight time and sinus disease. RESULTS: A total of 579 participants met the inclusion criteria for this study, with cohort prevalence of sinusitis, asthma, and rhinitis of 25.3%, 14.4%, and 20.5%, respectively. Tertiles 2 and 3 of working days per month were associated with higher RQS scores compared to tertile 1 (p for trend <0.01). Individual symptoms significantly associated with increasing number of working days per month included "need to blow nose," "sneezing," and "thick nasal discharge," and the number of international trips per month was significantly associated with "coughing" and "facial pain and pressure," among other symptoms. CONCLUSION: This is the largest study to analyze the relations between airline flight time and sinonasal disease. The results suggest a possible association between sinusitis diagnosis, symptom scores, and specific sinonasal symptoms, and airline flight time. PMID- 26834040 TI - Impact of grassland management regimes on bacterial endophyte diversity differs with grass species. AB - Most plant species are colonized by endophytic bacteria. Despite their importance for plant health and growth, the response of these bacteria to grassland management regimes is still not understood. Hence, we investigated the bacterial community structure in three agricultural important grass species Dactylis glomerata L., Festuca rubra L. and Lolium perenne L. with regard to fertilizer application and different mowing frequencies. For this purpose, above-ground plant material was collected from the Grassland Management Experiment (GrassMan) in Germany in September 2010 and 2011. DNA was extracted from surface-sterilized plant tissue and subjected to 16S rRNA gene PCRs. Endophytic community structures were assessed by denaturing gradient gel electrophoresis (DGGE)-based analysis of obtained PCR products. DGGE fingerprints revealed that fertilizer application significantly altered the endophytic communities in L. perenne and F. rubra but not in D. glomerata. Although no direct effect of mowing was observed, mowing frequencies in combination with fertilizer application had a significant impact on endophyte bacterial community structures. However, this effect was not observed for all three grass species in both years. Therefore, our results showed that management regimes changed the bacterial endophyte communities, but this effect was plant-specific and varied over time. SIGNIFICANCE AND IMPACT OF THE STUDY: Endophytic bacteria play an important role in plant health and growth. However, studies addressing the influence of grassland management regimes on these bacteria in above-ground plant parts are still missing. In this study, we present first evidence that fertilizer application significantly impacted bacterial community structures in three agricultural important grass species, whereas mowing had only a minor effect. Moreover, this effect was plant-specific and thus not visible for all grass species in each year. Consequently, this study sheds new light into the complex interaction of microbes and plants. PMID- 26834041 TI - Thoughts on Positive Selection in Thymus. AB - Any analysis of the mechanism of signalling during positive selection in the thymus is dependent on one's model of the TCR-ligand interaction. To date, thinking about mechanism has been dominated by what might be termed the Standard (or Centric) model, which is based on analogy between the BCR and the TCR. As the present analysis is an independent rationalized view of the TCR-ligand interactions, it permits a more balanced view of positive selection. The goal here was to explore this alternative to the Standard model. PMID- 26834042 TI - Unravelling Mechanistic Aspects of the Gas-Phase Ethanol Conversion: An Experimental and Computational Study on the Thermal Reactions of MO2 (+) (M=Mo, W) with Ethanol. AB - The ion/molecule reactions of molybdenum and tungsten dioxide cations with ethanol have been studied by Fourier transform ion-cyclotron resonance mass spectrometry (FT-ICR MS) and density functional theory (DFT) calculations. Dehydration of ethanol has been found as the dominant reaction channel, while generation of the ethyl cation corresponds to a minor product. Cleary, the reactions are mainly governed by the Lewis acidity of the metal center. Computational results, together with isotopic labeling experiments, show that the dehydration of ethanol can proceed either through a conventional concerted [1,2] elimination mechanism or a step-wise process; the latter occurs via a hydroxyethoxy intermediate. Formation of C2 H5 (+) takes place by transfer of OH( ) from ethanol to the metal center of MO2 (+) . The molybdenum and tungsten dioxide cations exhibit comparable reactivities toward ethanol, and this is reflected in similar reaction rate constants and branching ratios. PMID- 26834043 TI - Primary Melanoma of the Leptomeninges with BAP1 Expression-Loss in the Setting of a Nevus of Ota: A Clinical, Morphological and Genetic Study of 2 Cases. PMID- 26834044 TI - Cilostazol Improves Developmental Competence of Pig Oocytes by Increasing Intraoocyte Cyclic Adenosine Monophosphate Level and Delaying Meiotic Resumption. AB - Cilostazol (CLZ) is a cyclic adenosine monophosphate (cAMP) modulator that influences the steady state of the meiotic stage. This study was conducted to determine the effects of CLZ treatment during in vitro maturation (IVM) on developmental competence of pig oocytes. Immature oocytes were exposed to 0 (control), 0.5, 2 and 4 MUm CLZ during the first 22 h of IVM. Nuclear maturation, intraoocyte glutathione content and embryo cleavage after parthenogenesis (PA) and somatic cell nuclear transfer (SCNT) were not influenced by CLZ at any concentrations. However, 4 MUm CLZ significantly (p < 0.05) improved blastocyst formation after PA (52.1% vs 38.7-46.0%) and SCNT relative to other concentrations (40.8% vs 25.0-30.7%). The mean cell numbers of SCNT blastocysts were significantly increased by 4 MUm CLZ compared to the control (42.6 cells vs 35.3 cells/blastocyst). CLZ treatment significantly increased the intraoocyte cAMP level and effectively arrested oocytes at the germinal vesicle (GV) and GV break down stages compared to the control (74.5% vs 45.4%). Our results demonstrated that improved developmental competence of PA and SCNT pig embryos occurred via better synchronization of nuclear and cytoplasmic maturation induced by increased cAMP and delayed meiotic resumption after CLZ treatment. PMID- 26834045 TI - Identification of a syndrome comprising microcephaly and intellectual disability but not white matter disease associated with a homozygous c.676C>T p.R226W DEAF1 mutation. AB - We evaluated a 13-year-old East Pakistani male affected with microcephaly, apparent intellectual disability, hypotonia, and brisk reflexes without spasticity. His parents were first cousins. The patient also had a brother who was similarly affected and died at 10 years due to an accident. Previous SNP array testing showed a 1.63 Mb duplication at 16p13.11 of uncertain significance along with regions of homozygosity. Exome sequencing identified a known pathogenic homozygous alteration in DEAF1, c.676C>T (p.R226W), in this patient. The alteration had been reported in two individuals from a consanguineous Saudi Arabian family. Both individuals had microcephaly, intellectual disability, hypotonia, feeding difficulties, and poor growth. The patient reported here did not have evidence of white matter disease, as had been reported with prior patients. We conclude that this DEAF1 gene alteration caused this patient's symptoms and that white matter disease should not be considered a obligate feature of this syndrome. PMID- 26834046 TI - Cost-effectiveness of a pro-active approach of urinary incontinence in women. AB - OBJECTIVE: To estimate the cost-effectiveness and cost-utility of actively encouraging older community-dwelling women with urinary incontinence to be diagnosed and treated. DESIGN: The study was designed as cost-effectiveness and cost-utility analyses alongside a cluster randomised controlled trial. Analyses were performed from a societal perspective. Direct medical and nonmedical costs were taken into account and valued according to the standard Dutch guidelines for economic evaluations. SETTING: Primary care. POPULATION: Study participants were 350 community-dwelling women 55 years or older with urinary incontinence. METHODS: Women in the intervention group were invited for diagnostic testing and treatment. The control group received usual care according to the Dutch guideline on urinary incontinence. Follow-up period was 12 months. MAIN OUTCOME MEASURES: Incontinence Impact Adjusted Life Years (IIALY), Quality Adjusted Life Years (QALY) and incremental costs calculated per IIALY and per QALY gained. RESULTS: Costs per extra life year without impact on daily life from urinary incontinence amounted to ?5179 (95% CI -17 323 to 36 260). Costs per QALY amounted to ?23 907 (95% CI -124 849 to 121 849). Assuming a ceiling ratio of ?20 000, the probability that the intervention was cost-effective based on IIALYs was 91% and 46% based on QALYs. CONCLUSIONS: Improvements in severity of incontinence in older community-dwelling women can be achieved against reasonable costs, with an improvement of symptom-specific QALYs. Findings support an active role of primary care physicians towards women who hesitate to ask for help for urinary incontinence. TWEETABLE ABSTRACT: Encouraging women with urinary incontinence to be treated, improves symptoms and QOL against reasonable costs. PMID- 26834047 TI - Serum levels of neopterin, inflammatory markers and oxidative stress indicators in hyperemesis gravidarum. AB - AIM: To investigate whether serum levels of neopterin and inflammatory markers including C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and oxidative status indicators were altered in patients with hyperemesis gravidarum (HG) compared to asymptomatic pregnant women. METHODS: This cross-sectional study was performed including 30 pregnant women with HG (mean age: 30.67 +/- 6.68) and 30 asymptomatic pregnant women (mean age: 28.00 +/- 5.30). Demographic features, obstetric history, and the Pregnancy Unique Quantification of Emesis/Nausea (PUQE) index were noted. Complete blood count, serum biochemical assay and measurement of CRP, TNF-alpha, IL-6, total antioxidant status and total oxidative status (TOS) levels were taken and compared between groups. RESULTS: White blood cell count (P = 0.013), platelet count (P = 0.015), TOS (P < 0.001), and PUQE score (P < 0.001) were remarkably higher in HG pregnancies. On the other hand, serum levels of lactate dehydrogenase, (P < 0.001), sodium (P < 0.001), potassium (P < 0.001), chloride (P < 0.001) and TAS (P < 0.001) were higher in the control group. There was no difference in the levels of neopterin, CRP, TNF-alpha and IL-6. In patients with HG, a positive correlation was detected between TOS and serum levels of lactate dehydrogenase, while TNF-alpha, IL-6 and neopterin were positively correlated with hemoglobin levels. CONCLUSION: Our results demonstrated no association between inflammation and HG. Elucidation of the pathophysiology and complex interaction between various inflammatory processes in HG necessitates further trials on larger series. PMID- 26834048 TI - Quality assessment of traditional Chinese medicine herb couple by high performance liquid chromatography and mass spectrometry combined with chemometrics. AB - This study was designed to develop a simple, specific and reliable method to overall analyze the chemical constituents in clematidis radix et rhizome/notopterygii rhizome et radix herb couple using high-performance liquid chromatography coupled with tandem mass spectrometry and multiple chemometric analysis. First, the separation and qualitative analysis of herb couple was achieved on an Agilent Zorbax Eclipse Plus C18 column (250 mm * 4.6 mm, 5 MUm), and 69 compounds were unambiguously or tentatively identified. Moreover, in quantitative analysis, eight ingredients including six coumarins and two triterpenoid sapogenins were quantified by high-performance liquid chromatography coupled with tandem mass spectrometry. In terms of good linearity (r(2) >= 0.9995) with a relatively wide concentration range, recovery (85.40-102.50%) and repeatability (0.99-4.45%), the validation results suggested the proposed method was reliable, and successfully used to analyze ten batches of herb couple samples. Then, hierarchical cluster analysis and principal component analysis were used to classify samples and search significant ingredients. The results showed that ten batches of herb couple samples were classified into three groups, and six compounds were found for its better quality control. PMID- 26834049 TI - High mobility group box 1 is increased in the sera of psoriatic patients with disease progression. AB - BACKGROUND: Psoriasis vulgaris (PV) is an autoimmune-related chronic inflammatory disease, which appears mostly in skin, but also affects the vascular and metabolic system. The incidence of PV is 2-3% in the general population and there is still no possibility to cure. Trigger factors have been identified to initiate and maintain inflammation in the skin, which is characterized by Th1-, Th17- and Th22- cells. OBJECTIVE: We hypothesize that the damage-associated molecular pattern (DAMP) molecule high mobility group box 1 (HMGB1) plays a role in the pathogenesis of PV. HMGB1 is a DNA-binding protein located in the nucleus, which acquires cytokine-like properties once released from the cell upon necrotic cell death or actively secreted by immune cells in inflammation and cancer. METHODS: We recruited 90 psoriatic patients under and without therapy with mild, intermediate and severe progression of disease, defined by the Psoriasis Area Severity Index. Serum levels of HMGB1 in patients with PV were detected by enzyme linked immunosorbent assay (ELISA). RESULTS: Our results show an increased level of HMGB1 in the sera of patients with PV in comparison to healthy donors. Furthermore, our analyses reveal that HMGB1 levels are significantly increased with disease progression and are downregulated after standard therapies for PV have been conducted. CONCLUSION: Our data provide insights into a possible role of HMGB1 for inflammation in PV. PMID- 26834050 TI - Calibration of the Spanish PROMIS Smoking Item Banks. AB - INTRODUCTION: The Patient-Reported Outcomes Measurement Information System (PROMIS) Smoking Initiative has developed item banks for assessing six smoking behaviors and biopsychosocial correlates of smoking among adult cigarette smokers. The goal of this study is to evaluate the performance of the Spanish version of the PROMIS smoking item banks as compared to the original banks developed in English. METHODS: The six PROMIS banks for daily smokers were translated into Spanish and administered to a sample of Spanish-speaking adult daily smokers in the United States (N = 302). We first evaluated the unidimensionality of each bank using confirmatory factor analysis. We then conducted a two-group item response theory calibration, including an item response theory-based Differential Item Functioning (DIF) analysis by language of administration (Spanish vs. English). Finally, we generated full bank and short form scores for the translated banks and evaluated their psychometric performance. RESULTS: Unidimensionality of the Spanish smoking item banks was supported by confirmatory factor analysis results. Out of a total of 109 items that were evaluated for language DIF, seven items in three of the six banks were identified as having levels of DIF that exceeded an established criterion. The psychometric performance of the Spanish daily smoker banks is largely comparable to that of the English versions. CONCLUSIONS: The Spanish PROMIS smoking item banks are highly similar, but not entirely equivalent, to the original English versions. The parameters from these two-group calibrations can be used to generate comparable bank scores across the two language versions. IMPLICATIONS: In this study, we developed a Spanish version of the PROMIS smoking toolkit, which was originally designed and developed for English speakers. With the growing Spanish-speaking population, it is important to make the toolkit more accessible by translating the items and calibrating the Spanish version to be comparable with English-language scores. This study provided the translated item banks and short forms, comparable unbiased scores for Spanish speakers and evaluations of the psychometric properties of the new Spanish toolkit. PMID- 26834051 TI - Feasibility of Electronic Nicotine Delivery Systems in Surgical Patients. AB - INTRODUCTION: Cigarette smoking is a known risk factor for postoperative complications. Quitting or cutting down on cigarettes around the time of surgery may reduce these risks. This study aimed to determine the feasibility of using electronic nicotine delivery systems (ENDS) to help patients achieve this goal, regardless of their intent to attempt long-term abstinence. METHODS: An open label observational study was performed of cigarette smoking adults scheduled for elective surgery at Mayo Clinic Rochester and seen in the pre-operative evaluation clinic between December 2014 and June 2015. Subjects were given a supply of ENDS to use prior to and 2 weeks after surgery. They were encouraged to use them whenever they craved a cigarette. Daily use of ENDS was recorded, and patients were asked about smoking behavior and ENDS use at baseline, 14 days and 30 days. RESULTS: Of the 105 patients approached, 80 (76%) agreed to participate; five of these were later excluded. Among the 75, 67 (87%) tried ENDS during the study period. At 30-day follow-up, 34 (51%) who had used ENDS planned to continue using them. Average cigarette consumption decreased from 15.6 per person/d to 7.6 over the study period (P < .001). At 30 days, 11/67 (17%) reported abstinence from cigarettes. CONCLUSION: ENDS use is feasible in adult smokers scheduled for elective surgery and is associated with a reduction in perioperative cigarette consumption. These results support further exploration of ENDS as a means to help surgical patients reduce or eliminate their cigarette consumption around the time of surgery. IMPLICATIONS: Smoking in the perioperative period increases patients' risk for surgical complications and healing difficulties, but new strategies are needed to help patients quit or cut down during this stressful time. These pilot data suggest that ENDS use is feasible and well-accepted in surgical patients, and worthy of exploration as a harm reduction strategy in these patients. PMID- 26834052 TI - Brief Tailored Smoking Cessation Counseling in a Lung Cancer Screening Population is Feasible: A Pilot Randomized Controlled Trial. AB - INTRODUCTION: Maximizing smoking abstinence in lung cancer screening participants is important to reduce individual risk of disease and improve screening cost effectiveness; however, the optimal strategy remains undefined. We hypothesized that a single session of tailored face-to-face counseling on the day of screening CT scan, coupled with audio and printed cessation information would be feasible to deliver in a CT screening trial. METHODS: We randomized volunteer smokers in the Queensland Lung Cancer Screening Study to intervention (counseling session, audio quit materials, printed quit materials, Quitline contact details) or control group (printed quit materials, Quitline contact details). Participants self-reported point prevalence quit rates at 1 year. RESULTS: Fifty-five smokers were enrolled; 28 randomized to intervention and 27 controls. Median cigarette consumption was 25/day; 54/55 smoked at least 15 cigarettes per day. Median smoking duration was 46 years. Median Fagerstrom dependence score was 6. In total 58% did not report any quit attempt in the prior 12 months. Mean duration of counseling was 26.5 minutes. After 1 year, four participants (14.3%) in the intervention group and five participants (18.5%) in the control group had quit (P = .74). Combined annual point prevalence quit rate was 16.4%. CONCLUSIONS: Although feasible to deliver a single session of tailored counseling on the day of screening this intervention had no discernible impact on cessation over and above printed materials and Quitline access. As participants exhibited hardcore smoking characteristics, more intensive strategies, in larger cohorts, should be explored. IMPLICATIONS: The optimal smoking cessation strategy within a lung cancer screening program is not known. This study demonstrates that a single session of counseling can be feasibly delivered on the day of screening but may not have been intensive enough for long-term, hard-core smokers. PMID- 26834054 TI - Total Syntheses of (+)-Grandilodine C and (+)-Lapidilectine B and Determination of their Absolute Stereochemistry. AB - Enantioselective total syntheses of the Kopsia alkaloids (+)-grandilodine C and (+)-lapidilectine B were accomplished. A key intermediate, spirodiketone, was synthesized in 3 steps and converted into the chiral enone by enantioselective deprotonation followed by oxidation with up to 76 % ee. Lactone formation was achieved through stereoselective vinylation followed by allylation and ozonolysis. The total synthesis of (+)-grandilodine C was achieved by palladium catalyzed intramolecular allylic amination and ring-closing metathesis to give 8- and 5-membered heterocycles, respectively. Selective reduction of a lactam carbonyl gave (+)-lapidilectine B. The absolute stereochemistry of both natural products was thereby confirmed. These syntheses enable the scalable preparation of the above alkaloids for biological studies. PMID- 26834053 TI - Investigating hyperoxic effects in the rat brain using quantitative susceptibility mapping based on MRI phase. AB - PURPOSE: To test whether susceptibility imaging can detect microvenous oxygen saturation changes, induced by hyperoxia, in the rat brain. METHODS: A three dimensional gradient-echo with a flow compensation sequence was used to acquire T2*-weighted images of rat brains during hyperoxia and normoxia. Quantitative susceptibility mapping (QSM) and QSM-based microvenous oxygenation venography were computed from gradient-echo (GRE) phase images and compared between the two conditions. Pulse oxygen saturation (SpO2 ) in the cortex was examined and compared with venous oxygen saturation (SvO2 ) estimated by QSM. Oxygen saturation change calculated by a conventional Delta R2* map was also compared with the DeltaSvO2 estimated by QSM. RESULTS: Susceptibilities of five venous and tissue regions were quantified separately by QSM. Venous susceptibility was reduced by nearly 10%, with an SvO2 shift of 10% during hyperoxia. A hyperoxic effect, confirmed by SpO2 measurement, resulted in an SvO2 increase in the cortex. The DeltaSvO2 between hyperoxia and normoxia was consistent with what was estimated by the Delta R2* map in five regions. CONCLUSION: These findings suggest that a quantitative susceptibility map is a promising technique for SvO2 measurement. This method may be useful for quantitatively investigating oxygenation-dependent functional MRI studies. Magn Reson Med 77:592-602, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26834055 TI - Cardiac Surveillance Guidelines for Trastuzumab-Containing Therapy in Early-Stage Breast Cancer: Getting to the Heart of the Matter. PMID- 26834056 TI - Anthracyclines and Alkylating Agents: New Risk Factors for Breast Cancer in Childhood Cancer Survivors? PMID- 26834057 TI - Comparative Effectiveness of Minimally Invasive Hysterectomy for Endometrial Cancer. AB - PURPOSE: Despite the potential benefits of minimally invasive hysterectomy for uterine cancer, population-level data describing the procedure's safety in unselected patients are lacking. We examined the use of minimally invasive surgery and the association between the route of the procedure and long-term survival. METHODS: We used the SEER-Medicare database to identify women with stage I-III uterine cancer who underwent hysterectomy from 2006 to 2011. Patients who underwent abdominal hysterectomy were compared with those who had minimally invasive hysterectomy (laparoscopic and robot-assisted). Perioperative morbidity, use of adjuvant therapy, and long-term survival were examined after propensity score balancing. RESULTS: We identified 6,304 patients, including 4,139 (65.7%) who underwent abdominal hysterectomy and 2,165 (34.3%) who underwent minimally invasive hysterectomy; performance of minimally invasive hysterectomy increased from 9.3% in 2006 to 61.7% in 2011. Robot-assisted procedures accounted for 62.3% of the minimally invasive operations. Compared with women who underwent abdominal hysterectomy, minimally invasive hysterectomy was associated with a lower overall complication rate (22.7% v 39.7%; P < .001), and lower perioperative mortality (0.6% v 1.1%), but these women were more likely to receive adjuvant pelvic radiotherapy (34.3% v 31.3%) and brachytherapy (33.6% v 31.0%; P < .05). The complication rate was higher after robot-assisted hysterectomy compared with laparoscopic hysterectomy (23.7% v 19.5%; P = .03). There was no association between the use of minimally invasive hysterectomy and either overall (HR, 0.89; 95% CI, 0.75 to 1.04) or cancer-specific (HR, 0.83; 95% CI, 0.59 to 1.16) mortality. CONCLUSION: Minimally invasive hysterectomy does not appear to compromise long-term survival for women with endometrial cancer. PMID- 26834059 TI - Reply to F.M. Muggia. PMID- 26834060 TI - Oncogastroenterology. PMID- 26834058 TI - Translational Breast Cancer Research Consortium (TBCRC) 022: A Phase II Trial of Neratinib for Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases. AB - PURPOSE: Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the CNS are limited. Neratinib is an irreversible inhibitor of erbB1, HER2, and erbB4, with promising activity in HER2 positive breast cancer; however, its activity in the CNS is unknown. We evaluated the efficacy of treatment with neratinib in patients with HER2-positive breast cancer brain metastases in a multicenter, phase II open-label trial. PATIENTS AND METHODS: Eligible patients were those with HER2-positive brain metastases (>= 1 cm in longest dimension) who experienced progression in the CNS after one or more line of CNS-directed therapy, such as whole-brain radiotherapy, stereotactic radiosurgery, and/or surgical resection. Patients received neratinib 240 mg orally once per day, and tumors were assessed every two cycles. The primary endpoint was composite CNS objective response rate (ORR), requiring all of the following: >= 50% reduction in volumetric sum of target CNS lesions and no progression of non-target lesions, new lesions, escalating corticosteroids, progressive neurologic signs/symptoms, or non-CNS progression--the threshold for success was five of 40 responders. RESULTS: Forty patients were enrolled between February 2012 and June 2013; 78% of patients had previous whole-brain radiotherapy. Three women achieved a partial response (CNS objective response rate, 8%; 95% CI, 2% to 22%). The median number of cycles received was two (range, one to seven cycles), with a median progression-free survival of 1.9 months. Five women received six or more cycles. The most common grade >= 3 event was diarrhea (occurring in 21% of patients taking prespecified loperamide prophylaxis and 28% of those without prophylaxis). Patients in the study experienced a decreased quality of life over time. CONCLUSION: Although neratinib had low activity and did not meet our threshold for success, 12.5% of patients received six or more cycles. Studies combining neratinib with chemotherapy in patients with CNS disease are ongoing. PMID- 26834061 TI - Intraperitoneal Therapy for Ovarian Cancer. PMID- 26834062 TI - Reply to F.M. Muggia. PMID- 26834063 TI - Long-Term Neurocognitive Functioning and Social Attainment in Adult Survivors of Pediatric CNS Tumors: Results From the St Jude Lifetime Cohort Study. AB - PURPOSE: To assess the prevalence and severity of neurocognitive impairment in adult survivors of pediatric CNS tumors and to examine associated treatment exposures. PATIENTS AND METHODS: Participants included 224 survivors of CNS tumors who were treated at St Jude Children's Research Hospital (current median age [range], 26 years [19 to 53 years]; time from diagnosis, 18 years [11 to 42 years]) and completed neurocognitive testing. Information on cranial radiation therapy (CRT) doses and parameters of delivery were abstracted from medical records. The prevalence of severe impairment (ie, at least two standard deviations below normative mean) was compared across radiation treatment groups (no CRT, focal irradiation, craniospinal irradiation) using the chi(2) test. Log binomial models were used to estimate risk ratios (RRs) and corresponding 95% CIs for severe impairment. RESULTS: In multivariable models, craniospinal irradiation was associated with a 1.5- to threefold increased risk of severe impairment compared with no CRT (eg, intelligence: RR = 2.70; 95% CI, 1.37 to 5.34; memory: RR = 2.93; 95% CI, 1.69 to 5.08; executive function: RR = 1.74; 95% CI, 1.24 to 2.45). Seizures were associated with impaired academic performance (RR = 1.48; 95% CI, 1.02 to 2.14), attention (RR = 1.54; 95% CI, 1.12 to 2.13), and memory (RR = 1.44; 95% CI, 1.04 to 1.99). Hydrocephalus with shunt placement was associated with impaired intelligence (RR = 1.78; 95% CI, 1.12 to 2.82) and memory (RR = 1.42; 95% CI, 1.03 to 1.95). Differential follow-up time contributed to variability in prevalence estimates between survivors treated with older nonconformal and those treated with more contemporary conformal radiation therapy methods. Neurocognitive impairment was significantly associated with lower educational attainment, unemployment, and nonindependent living. CONCLUSION: Survivors of pediatric CNS tumors are at risk of severe neurocognitive impairment in adulthood. The prevalence of severe impairment is greater than expected in the general population, even in the absence of CRT, and is associated with disrupted attainment of adult social milestones. PMID- 26834065 TI - Cardiovascular Disease Among Survivors of Adult-Onset Cancer: A Community-Based Retrospective Cohort Study. AB - PURPOSE: Cardiovascular diseases (CVDs), including ischemic heart disease, stroke, and heart failure, are well-established late effects of therapy in survivors of childhood and young adult (< 40 years at diagnosis) cancers; less is known regarding CVD in long-term survivors of adult-onset (>= 40 years) cancer. METHODS: A retrospective cohort study design was used to describe the magnitude of CVD risk in 36,232 >= 2-year survivors of adult-onset cancer compared with matched (age, sex, and residential ZIP code) noncancer controls (n = 73,545) within a large integrated managed care organization. Multivariable regression was used to examine the impact of cardiovascular risk factors (CVRFs; hypertension, diabetes, dyslipidemia) on long-term CVD risk in cancer survivors. RESULTS: Survivors of multiple myeloma (incidence rate ratio [IRR], 1.70; P < .01), carcinoma of the lung/bronchus (IRR, 1.58; P < .01), non-Hodgkin lymphoma (IRR, 1.41; P < .01), and breast cancer (IRR, 1.13; P < .01) had significantly higher CVD risk when compared with noncancer controls. Conversely, prostate cancer survivors had a lower CVD risk (IRR, 0.89; P < .01) compared with controls. Cancer survivors with two or more CVRFs had the highest risk of CVD when compared with noncancer controls with less than two CVRFs (IRR, 1.83 to 2.59; P < .01). Eight-year overall survival was significantly worse among cancer survivors who developed CVD (60%) when compared with cancer survivors without CVD (81%; P < .01). CONCLUSION: The magnitude of subsequent CVD risk varies according to cancer subtype and by the presence of CVRFs. Overall survival in survivors who develop CVD is poor, emphasizing the need for targeted prevention strategies for individuals at highest risk of developing CVD. PMID- 26834064 TI - Patient Prognostic Score and Associations With Survival Improvement Offered by Radiotherapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ: A Population-Based Longitudinal Cohort Study. AB - PURPOSE: Radiotherapy (RT) after breast-conserving surgery (BCS) is a standard treatment option for the management of ductal carcinoma in situ (DCIS). We sought to determine the survival benefit of RT after BCS on the basis of risk factors for local recurrence. PATIENTS AND METHODS: A retrospective longitudinal cohort study was performed to identify patients with DCIS diagnosed between 1988 and 2007 and treated with BCS by using SEER data. Patients were divided into the following two groups: BCS+RT (RT group) and BCS alone (non-RT group). We used a patient prognostic scoring model to stratify patients on the basis of risk of local recurrence. We performed a Cox proportional hazards model with propensity score weighting to evaluate breast cancer mortality between the two groups. RESULTS: We identified 32,144 eligible patients with DCIS, 20,329 (63%) in the RT group and 11,815 (37%) in the non-RT group. Overall, 304 breast cancer-specific deaths occurred over a median follow-up of 96 months, with a cumulative incidence of breast cancer mortality at 10 years in the weighted cohorts of 1.8% (RT group) and 2.1% (non-RT group; hazard ratio, 0.73; 95% CI, 0.62 to 0.88). Significant improvements in survival in the RT group compared with the non-RT group were only observed in patients with higher nuclear grade, younger age, and larger tumor size. The magnitude of the survival difference with RT was significantly correlated with prognostic score (P < .001). CONCLUSION: In this population-based study, the patient prognostic score for DCIS is associated with the magnitude of improvement in survival offered by RT after BCS, suggesting that decisions for RT could be tailored on the basis of patient factors, tumor biology, and the prognostic score. PMID- 26834068 TI - Development of a CO2 -releasing coformulation based on starch, Saccharomyces cerevisiae and Beauveria bassiana attractive towards western corn rootworm larvae. AB - BACKGROUND: CO2 is known as an attractant for many soil-dwelling pests. To implement an attract-and-kill strategy for soil pest control, CO2 -emitting formulations need to be developed. The aim of the present work was to develop a slow-release bead system in order to bridge the gap between application and hatching of western corn rootworm larvae. RESULTS: We compared different Ca alginate beads containing Saccharomyces cerevisiae for their potential to release CO2 over a period of several weeks. The addition of starch improved CO2 release, resulting in significantly higher CO2 concentrations in soil for at least 4 weeks. The missing amylase activity was compensated for either by microorganisms present in the soil or by coencapsulation of Beauveria bassiana. Formulations containing S. cerevisiae, starch and B. bassiana were attractive for western corn rootworm larvae within the first 4 h following exposure; however, when considering the whole testing period, the maize root systems remained more attractive for the larvae. CONCLUSION: Coencapsulation of S. cerevisiae, starch and B. bassiana is a promising approach for the development of attractive formulations for soil applications. For biological control strategies, the attractiveness needs to be increased by phagostimuli to extend contact between larvae and the entomopathogenic fungus growing out of these formulations. (c) 2016 Society of Chemical Industry. PMID- 26834067 TI - Randomized Trial of Hepatic Artery Embolization for Hepatocellular Carcinoma Using Doxorubicin-Eluting Microspheres Compared With Embolization With Microspheres Alone. AB - PURPOSE: Transarterial chemoembolization is accepted therapy for hepatocellular carcinoma (HCC). No randomized trial has demonstrated superiority of chemoembolization compared with embolization, and the role of chemotherapy remains unclear. This randomized trial compares the outcome of embolization using microspheres alone with chemoembolization using doxorubicin-eluting microspheres. MATERIALS AND METHODS: At a single tertiary referral center, patients with HCC were randomly assigned to embolization with microspheres alone (Bead Block [BB]) or loaded with doxorubicin 150 mg (LC Bead [LCB]). Random assignment was stratified by number of embolizations to complete treatment, and assignments were generated by permuted blocks in the institutional database. The primary end point was response according to RECIST 1.0 (Response Evaluation Criteria in Solid Tumors) using multiphase computed tomography 2 to 3 weeks post-treatment and then at quarterly intervals, with the reviewer blinded to treatment allocation. Secondary objectives included safety and tolerability, time to progression, progression-free survival, and overall survival. This trial is currently closed to accrual. RESULTS: Between December 2007 and April 2012, 101 patients were randomly assigned: 51 to BB and 50 to LCB. Demographics were comparable: median age, 67 years; 77% male; and 22% Barcelona Clinic Liver Cancer stage A and 78% stage B or C. Adverse events occurred with similar frequency in both groups: BB, 19 of 51 patients (38%); LCB, 20 of 50 patients (40%; P = .48), with no difference in RECIST response: BB, 5.9% versus LCB, 6.0% (difference, -0.1%; 95% CI, -9% to 9%). Median PFS was 6.2 versus 2.8 months (hazard ratio, 1.36; 95% CI, 0.91 to 2.05; P = .11), and overall survival, 19.6 versus 20.8 months (hazard ratio, 1.11; 95% CI, 0.71 to 1.76; P = .64) for BB and LCB, respectively. CONCLUSION: There was no apparent difference between the treatment arms. These results challenge the use of doxorubicin-eluting beads for chemoembolization of HCC. PMID- 26834066 TI - Prognostic Effect of Tumor Lymphocytic Infiltration in Resectable Non-Small-Cell Lung Cancer. AB - PURPOSE: Tumor lymphocytic infiltration (TLI) has differing prognostic value among various cancers. The objective of this study was to assess the effect of TLI in lung cancer. PATIENTS AND METHODS: A discovery set (one trial, n = 824) and a validation set (three trials, n = 984) that evaluated the benefit of platinum-based adjuvant chemotherapy in non-small-cell lung cancer were used as part of the LACE-Bio (Lung Adjuvant Cisplatin Evaluation Biomarker) study. TLI was defined as intense versus nonintense. The main end point was overall survival (OS); secondary end points were disease-free survival (DFS) and specific DFS (SDFS). Hazard ratios (HRs) and 95% CIs associated with TLI were estimated through a multivariable Cox model in both sets. TLI-histology and TLI-treatment interactions were explored in the combined set. RESULTS: Discovery and validation sets with complete data included 783 (409 deaths) and 763 (344 deaths) patients, respectively. Median follow-up was 4.8 and 6 years, respectively. TLI was intense in 11% of patients in the discovery set compared with 6% in the validation set (P < .001). The prognostic value of TLI in the discovery set (OS: HR, 0.56; 95% CI, 0.38 to 0.81; P = .002; DFS: HR, 0.59; 95% CI, 0.42 to 0.83; P = .002; SDFS: HR, 0.56; 95% CI, 0.38 to 0.82; P = .003) was confirmed in the validation set (OS: HR, 0.45; 95% CI, 0.23 to 0.85; P = .01; DFS: HR, 0.44; 95% CI, 0.24 to 0.78; P = .005; SDFS: HR, 0.42; 95% CI, 0.22 to 0.80; P = .008) with no heterogeneity across trials (P >= .38 for all end points). No significant predictive effect was observed for TLI (P >= .78 for all end points). CONCLUSION: Intense lymphocytic infiltration, found in a minority of tumors, was validated as a favorable prognostic marker for survival in resected non-small-cell lung cancer. PMID- 26834069 TI - Comprehensive Insights into the Reactivity of Electrolytes Based on Sodium Ions. AB - We report a systematic investigation of Na-based electrolytes that comprise various NaX [X=hexafluorophosphate (PF6 ), perchlorate (ClO4 ), bis(trifluoromethanesulfonyl)imide (TFSI), fluorosulfonyl (trifluoromethanesulfonyl)imide (FTFSI), and bis(fluorosulfonyl)imide (FSI)] salts and solvent mixtures [ethylene carbonate (EC)/dimethyl carbonate (DMC), EC/diethyl carbonate (DEC), and EC/propylene carbonate (PC)] with respect to the Al current collector stability, formation of soluble degradation compounds, reactivity towards sodiated hard carbon (Nax -HC), and solid-electrolyte interphase (SEI) layer formation. Cyclic voltammetry demonstrates that the stability of Al is highly influenced by the nature of the anions, solvents, and additives. GC-MS analysis reveals that the formation of SEI telltales depends on the nature of the linear alkyl carbonates and the battery chemistry (Li(+) vs. Na(+) ). FTIR spectroscopy shows that double alkyl carbonates are the main components of the SEI layer on Nax -HC. In the presence of Na salts, EC/DMC and EC/DEC presented a higher reactivity towards Nax -HC than EC/PC. For a fixed solvent mixture, the onset temperature follows the sequence NaClO4 =2 proteotypic peptides. The mass spectrometric proteome database of the human iris, ciliary body, and RPE/choroid may serve as a valuable resource for future investigations of the eye in health and disease. The MS proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD001424 and PXD002194. PMID- 26834088 TI - Effects of a novel marine probiotic, Lactobacillus plantarum AH 78, on growth performance and immune response of Nile tilapia (Oreochromis niloticus). AB - AIMS: Evaluation of the efficacy of marine lactic acid bacteria, Lactobacillus plantarum AH 78, on growth performance and immune response of Nile tilapia (Oreochromis niloticus) challenged with Aeromonas hydrophila. METHODS AND RESULTS: Marine probiotic, Lact. plantarum AH 78, was incorporated in Nile tilapia diets at 0.0, 0.5, 1.0 or 2.0% (w/w). The diets were fed to juvenile Nile tilapia for 40 days, after which they were challenged with pathogenic bacterium, Aer. hydrophila. The best growth rates and feed efficiency were obtained at 0.5% probiotic, while fish survival was not affected by dietary probiotic. After challenge with Aer. hydrophila immunological responses and survival were recorded at 1.0% probiont. Likewise, significant up-regulation of the expression of cytokine genes, IL-4, IL-12 and IFN-gamma, in fish livers was found at 1.0% probiont, compared to the control diet. Concomitantly, AH 78 colonized the intestinal mucosa of treated fish, even after reverting to the control diet, and remained viable in the feed stored at 4 degrees C up to 12 months. CONCLUSIONS: Marine Lact. plantarum AH 78 at 0.5-1.0% inclusion level conferred the best performance and immune response of Nile tilapia challenged with Aer. hydrophila. SIGNIFICANCE AND IMPACT OF THE STUDY: Marine Lact. plantarum AH 78 could be considered as a potential probiotic to control disease outbreaks in farmed Nile tilapia. PMID- 26834089 TI - The Continued Eclipse of Heterogeneity in Gerontological Research. AB - OBJECTIVES: After a long history of neglect, diversity among older people and increasing heterogeneity with age are now familiar ideas in gerontological discourse. We take up the question of whether this increased attention is translating into the domain of empirical research. We replicate Nelson and Dannefer's (1992) review of the treatment of age-based variability in gerontological research, the most recent known assessment of the issue. METHOD: A sample of empirical studies was drawn from six gerontological journals to determine (a) whether measures of within-age variability were reported and/or discussed and (b) if reported, the observed age-based pattern of variability in the outcome(s). RESULTS: The majority of studies neither reported nor discussed age-based variability. Among those that did report, the great majority indicated either stability or increasing variability with age. Observed patterns varied by outcome type. Although a majority of analyses of psychological and social outcomes suggested that variability was stable across age, half of the analyses of biological/health outcomes indicated increasing variability. Overall, very few (3%) of studies suggested decreasing variability. DISCUSSION: Consistent with earlier reports of studies, researchers continue to focus on average differences between age groups, yet key issues in social gerontology require attention to intra-age variability. PMID- 26834090 TI - Social Support, Mastery, and Psychological Distress in Black and White Older Adults. AB - Social support and mastery can protect against psychological distress in late life, carrying implications for theory and intervention. However, some groups have not been well studied, with African Americans receiving less empirical attention, especially in regard to their satisfaction with social support. In this study, samples of African American and White American community-dwelling older adults reported their perceived mastery, degree of psychological distress, and social support. A model investigating the separate relationships of these variables by race explained significantly more variance than a model for all participants combined. For both groups, mastery was significantly associated with lower psychological distress. However, among White Americans, social support was significantly associated with lower distress, while among African Americans, there was no relationship between satisfaction with social support and distress. The findings indicate that social support and mastery are important variables to consider in their relationship to psychological distress in later life and that diverse racial groups may display differing relationships among these variables. PMID- 26834091 TI - The Revised Child Anxiety and Depression Scale 25-Parent Version: Scale Development and Validation in a School-Based and Clinical Sample. AB - To help facilitate the dissemination and implementation of evidence-based assessment practices, we examined the psychometric properties of the shortened 25 item version of the Revised Child Anxiety and Depression Scale-parent report (RCADS-25-P), which was based on the same items as the previously published shortened 25-item child version. We used two independent samples of youth-a school sample ( N = 967, Grades 3-12) and clinical sample ( N = 433; 6-18 years) to examine the factor structure, reliability, and validity of the RCADS-25-P scale scores. Results revealed that the two-factor structure (i.e., depression and broad anxiety factor) fit the data well in both the school and clinical sample. All reliability estimates, including test-retest indices, exceeded benchmark for good reliability. In the school sample, the RCADS-25-P scale scores converged significantly with related criterion measures and diverged with nonrelated criterion measures. In the clinical sample, the RCADS-25-P scale scores successfully discriminated between those with and without target problem diagnoses. In both samples, child-parent agreement indices were in the expected ranges. Normative data were also reported. The RCADS-25-P thus demonstrated robust psychometric properties across both a school and clinical sample as an effective brief screening instrument to assess for depression and anxiety in children and adolescents. PMID- 26834092 TI - Imagination in narrative medicine: A case study in a children's hospital in Italy. AB - This article presents a qualitative study realized in the Children's University Hospital of Parma, Italy, aimed at observing the effects of the fictional narrative in the emotions of the young patients. The results showed that, especially by means of projection, identification and symbolization, the imagination helps the children to elaborate in a positive way the bad emotions elicited by the experience of the disease and of the stay in hospital. Furthermore, the study was useful to the healthcare professionals in order to understand the emotive, cognitive and relational needs of the patients. We suggest the introduction of creative expression in the narrative medicine in addition to the autobiographical accounts, the questionnaires and the interviews in some particular care contexts. PMID- 26834094 TI - A letter from Canada's new minister of health. PMID- 26834095 TI - Spontaneous rib fracture: consider other neoplastic causes. PMID- 26834096 TI - 18F-FDG PET/CT for Staging and Restaging of Breast Cancer. AB - Many studies have pointed out the role of (18)F-FDG PET/CT (or (18)F-FDG PET) in patients with clinical stage III or II breast cancer. (18)F-FDG PET/CT might advantageously replace other staging procedures, such as bone scanning and possibly contrast-enhanced CT of the thorax or abdomen-pelvis. We discuss the findings, locoregional or distant, that can be expected in different categories of breast cancer and their impact on prognosis and management. We also discuss the role of (18)F-FDG PET/CT in restaging and how (18)F-FDG PET/CT compares with conventional techniques in restaging for patients with suspected disease recurrence. We conclude with some recommendations for clinical practice and future research. PMID- 26834097 TI - Introduction and Overview. PMID- 26834098 TI - Imaging Bone Metastases in Breast Cancer: Staging and Response Assessment. AB - Bone metastases are common in patients with advanced breast cancer. Given the significant associated morbidity, the introduction of new, effective systemic therapies, and the improvement in survival time, early detection and response assessment of skeletal metastases have become even more important. Although planar bone scanning has recognized limitations, in particular, poor specificity in staging and response assessment, it continues to be the main method in current clinical practice for staging of the skeleton in patients at risk of bone metastases. However, the accuracy of bone scanning can be improved with the addition of SPECT/CT. There have been reported improvements in sensitivity and specificity for staging of the skeleton with either bone-specific PET/CT tracers, such as (18)F-NaF, or tumor-specific tracers, such as (18)F-FDG, although these methods are less widely available and more costly. There is a paucity of data on the use of (18)F-NaF PET/CT for response assessment in breast cancer, but there is increasing evidence that (18)F-FDG PET/CT may improve on current methods in this regard. At the same time, interest and experience in using whole-body morphologic MRI augmented with diffusion-weighted imaging for both staging and response assessment in the skeleton have been increasing. However, data on comparisons of these methods with PET methods to determine the best technique for current clinical practice or for clinical trials are insufficient. There are early data supporting the use (18)F-FDG PET/MRI to assess malignant disease in the skeleton, with the possibility of taking advantage of the synergies offered by combining morphologic, physiologic, and metabolic imaging. PMID- 26834100 TI - Quo Vadis: PET and Single-Photon Molecular Breast Imaging. PMID- 26834101 TI - Breast-Dedicated Radionuclide Imaging Systems. AB - Breast-dedicated radionuclide imaging systems show promise for increasing clinical sensitivity for breast cancer while minimizing patient dose and cost. We present several breast-dedicated coincidence-photon and single-photon camera designs that have been described in the literature and examine their intrinsic performance, clinical relevance, and impact. Recent tracer development is mentioned, results from recent clinical tests are summarized, and potential areas for improvement are highlighted. PMID- 26834102 TI - Nuclear Breast Imaging: Clinical Results and Future Directions. AB - Interest in nuclear breast imaging is increasing because of technical improvements in dedicated devices that allow the use of relatively low doses of radiotracers with high sensitivity for even small breast cancers. For women with newly diagnosed cancer, primary chemotherapy is often recommended, and improved methods of assessing treatment response are of interest. With widespread breast density notification, functional rather than anatomic methods of screening are of increasing interest as well. For a cancer imaging technology to be adopted, several criteria must be met that will be discussed: evidence of clinical benefit with minimal harm, standardized interpretive criteria, direct biopsy guidance, and acceptable cost-effectiveness. PMID- 26834099 TI - 18F-FDG PET/CT for Monitoring of Treatment Response in Breast Cancer. AB - Changes in tumor metabolic activity have been shown to be an early indicator of treatment effectiveness for breast cancer, mainly in the neoadjuvant setting. The histopathologic response at the completion of chemotherapy has been used as the reference standard for assessment of the accuracy of (18)F-FDG PET in predicting a response during systemic treatment. Although a pathologic complete response (pCR) remains an important positive prognostic factor for an individual patient, a recent metaanalysis could validate pCR as a surrogate marker for patient outcomes only in aggressive breast cancer subtypes. For establishment of the clinical application of metabolic treatment response studies, larger series of specific breast cancer subtypes-including hormone receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative breast cancers are necessary. In addition, thresholds for relative changes in (18)F-FDG uptake to distinguish between responding and nonresponding tumors need to be validated for different systemic treatment approaches, with progression-free survival and overall survival as references. A PET-based treatment stratification is applicable clinically only if valid alternative therapies are available. Of note, patients who do not achieve a pCR might still benefit from neoadjuvant therapy enabling breast-conserving surgery. In the metastatic setting, residual tumor metabolic activity after the initiation of systemic therapy is an indicator of active disease, whereas a complete resolution of metabolic activity is predictive of a successful treatment response. PMID- 26834103 TI - Molecular Imaging of Biomarkers in Breast Cancer. AB - The success of breast cancer therapy is ultimately defined by clinical endpoints such as survival. It is valuable to have biomarkers that can predict the most efficacious therapies or measure response to therapy early in the course of treatment. Molecular imaging has a promising role in complementing and overcoming some of the limitations of traditional biomarkers by providing the ability to perform noninvasive, repeatable whole-body assessments. The potential advantages of imaging biomarkers are obvious and initial clinical studies have been promising, but proof of clinical utility still requires prospective multicenter clinical trials. PMID- 26834105 TI - Novel Strategies for Breast Cancer Imaging: New Imaging Agents to Guide Treatment. AB - The development of molecular therapies for cancer treatment has created a need to image biochemical and molecular processes to appropriately select tumors that express the drug target, thereby predicting a positive response to therapy. Biomarker-driven molecular imaging is complementary to pathologic analysis and offers a more direct measure of drug efficacy and treatment response, potentially providing early insight into therapeutic futility and allowing response-adapted treatment strategies. Imaging also allows a unique means of assessing the heterogeneity of both intra- and intertumoral targets as well as a mixed response to therapy; this information is important in the setting of metastatic disease. Here we review the development of novel molecular imaging probes and combinations of probes to guide therapy for two new targets and associated therapeutic agents: cyclin-dependent kinase inhibitors and poly(adenosine diphosphate-ribose) polymerase inhibitors. PMID- 26834104 TI - Mouse Models of Breast Cancer: Platforms for Discovering Precision Imaging Diagnostics and Future Cancer Medicine. AB - Representing an enormous health care and socioeconomic challenge, breast cancer is the second most common cancer in the world and the second most common cause of cancer-related death. Although many of the challenges associated with preventing, treating, and ultimately curing breast cancer are addressable in the laboratory, successful translation of groundbreaking research to clinical populations remains an important barrier. Particularly when compared with research on other types of solid tumors, breast cancer research is hampered by a lack of tractable in vivo model systems that accurately recapitulate the relevant clinical features of the disease. A primary objective of this article was to provide a generalizable overview of the types of in vivo model systems, with an emphasis primarily on murine models, that are widely deployed in preclinical breast cancer research. Major opportunities to advance precision cancer medicine facilitated by molecular imaging of preclinical breast cancer models are discussed. PMID- 26834107 TI - Imaging Diagnostic and Therapeutic Targets: Human Epidermal Growth Factor Receptor 2. AB - Since the approval of trastuzumab, a humanized monoclonal antibody against the extracellular domain of human epidermal growth factor receptor 2 (HER2), 3 other HER2-targeting agents have gained regulatory approval: lapatinib, pertuzumab, and trastuzumab-emtansine. These agents have revolutionized the management of HER2 positive breast cancer, highlighting the concept that targeted therapies are successful when patients exhibit tumor-selective expression of a molecular target in this case, HER2. However, response prediction and innate or acquired resistance remain serious concerns. Predictive biomarkers of a response-which could help in the selection of patients who might benefit from a selected targeted therapy-are currently lacking. Molecular imaging with anti-HER2 probes allows the noninvasive, whole-body assessment of HER2 tumor burden and has the potential to improve patient selection, optimize the dose and schedule, and rationalize assessment of the response to anti-HER2 therapies. Furthermore, unlike biopsy-based HER2 assessment, this approach can reveal inter- or intratumoral heterogeneity as well as variations in HER2 expression over time. This review summarizes the available literature and the current status of molecular imaging as a tool for the assessment of HER2 (target) expression or the prediction of an early treatment response in early and advanced HER2-positive breast cancer. PMID- 26834108 TI - The Use of Novel PET Tracers to Image Breast Cancer Biologic Processes Such as Proliferation, DNA Damage and Repair, and Angiogenesis. AB - The balance between proliferation and cell death is pivotal to breast tumor growth. Because of a combination of environmental and genetic factors leading to activation of oncogenes or inactivation of tumor suppressor genes, these processes become deregulated in cancer. PET imaging of proliferation, angiogenesis, and DNA damage and repair offers the opportunity to monitor therapeutic efficacy to detect changes in tumor biology that may precede physical size reduction and simultaneously allows the study of intratumoral and intertumoral heterogeneity.This review examines recent developments in breast cancer imaging using novel probes. The probes discussed here are not licensed for routine use and are at various stages of development ranging from preclinical development (e.g., the DNA repair marker gammaH2AX) to clinical validation in larger studies (such as the proliferation probe 3'-deoxy-3'-(18)F-fluorothymidine [(18)F-FLT]). In breast cancer, most studies have focused on proliferation imaging mainly based on (18)F-labeled thymidine analogs. Initial studies have been promising; however, the results of larger validation studies are necessary before being incorporated into routine clinical use. Although there are distinct advantages in using process-specific probes, properties such as metabolism need careful consideration, because high background uptake in the liver due to glucuronidation in the case of (18)F-FLT may limit utility for imaging of liver metastases.Targeting angiogenesis has had some success in tumors such as renal cell carcinoma; however, angiogenesis inhibitors have not been particularly successful in the clinical treatment of breast cancer. This could be potentially attributed to patient selection due to the lack of validated predictive and responsive biomarkers; the quest for a successful noninvasive biomarker for angiogenesis could solve this challenge. Finally, we look at cell death including apoptosis and DNA damage and repair probes, the most well-studied example being (18)F-annexin V; more recently, probes that target caspase endoproteases have been developed and are undergoing early clinical validation studies.Further clinical studies including analysis of test-retest variability are essential to determine sensitivity and future utility of these probes in breast cancer. PMID- 26834106 TI - Imaging Diagnostic and Therapeutic Targets: Steroid Receptors in Breast Cancer. AB - Estrogen receptor alpha (ERalpha) and progesterone receptor (PR) are important steroid hormone receptor biomarkers used to determine prognosis and to predict benefit from endocrine therapies for breast cancer patients. Receptor expression is routinely measured in biopsy specimens using immunohistochemistry, although such testing can be challenging, particularly in the setting of metastatic disease. ERalpha and PR can be quantitatively assayed noninvasively with PET. This approach provides the opportunity to assess receptor expression and function in real time, within the entire tumor, and across distant sites of metastatic disease. This article reviews the current evidence of ERalpha and PR PET imaging as predictive and early-response biomarkers for endocrine therapy. PMID- 26834109 TI - Translation of New Molecular Imaging Approaches to the Clinical Setting: Bridging the Gap to Implementation. AB - Molecular imaging with PET is a rapidly emerging technique. In breast cancer patients, more than 45 different PET tracers have been or are presently being tested. With a good rationale, after development of the tracer and proven feasibility, it is of interest to evaluate whether there is a potential meaningful role for the tracer in the clinical setting-such as in staging, in the (early) prediction of a treatment response, or in supporting drug choices. So far, only (18)F-FDG PET has been incorporated into breast cancer guidelines. For proof of the clinical relevance of tracers, especially for analysis in a multicenter setting, standardization of the technology and access to the novel PET tracer are required. However, resources for PET implementation research are limited. Therefore, next to randomized studies, novel approaches are required for proving the clinical value of PET tracers with the smallest possible number of patients. The aim of this review is to describe the process of the development of PET tracers and the level of evidence needed for the use of these tracers in breast cancer. Several breast cancer trials have been performed with the PET tracers (18)F-FDG, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), and (18)F fluoroestradiol ((18)F-FES). We studied them to learn lessons for the implementation of novel tracers. After defining the gap between a good rationale for a tracer and implementation in the clinical setting, we propose solutions to fill the gap to try to bring more PET tracers to daily clinical practice. PMID- 26834110 TI - Clinical Diagnosis and Management of Breast Cancer. AB - The diagnosis and management of breast cancer are undergoing a paradigm shift from a one-size-fits-all approach to an era of personalized medicine. Sophisticated diagnostics, including molecular imaging and genomic expression profiles, enable improved tumor characterization. These diagnostics, combined with newer surgical techniques and radiation therapies, result in a collaborative multidisciplinary approach to minimizing recurrence and reducing treatment associated morbidity. This article reviews the diagnosis and treatment of breast cancer, including screening, staging, and multidisciplinary management. PMID- 26834111 TI - Response to "Best (but oft forgotten) practices: testing for treatment effects in randomized trials by separate analyses of changes from baseline in each group is a misleading approach". PMID- 26834112 TI - Reply to KL Stanhope and PJ Havel. PMID- 26834115 TI - Individualized Radiation Dose Escalation Based on the Decrease in Tumor FDG Uptake and Normal Tissue Constraints Improve Survival in Patients With Esophageal Carcinoma. AB - BACKGROUND: To determine whether individualized radiation dose escalation after planned chemoradiation based on the decrease in tumor and normal tissue constraints can improve survival in patients with esophageal carcinoma. METHODS: From August 2005 to December 2010, 112 patients with squamous esophageal carcinoma were treated with radical concurrent chemoradiation. Patients received positron emission tomography-computer tomography scan twice, before radiation and after radiation dose of 50.4 Gy. All patients were noncomplete metabolic response groups according to the Response Evaluation Criteria in solid tumors. Only 52 patients with noncomplete metabolic response received individualized dose escalation based on tumor and normal tissue constraints. Survival and treatment failure were observed and analyzed using SPSS (13.0). RESULTS: The rate of complete metabolic response for patients with noncomplete metabolic response after dose escalation reached 17.3% (9 of 52). The 2-year overall survival rates for patients with noncomplete metabolic response in the conventional and dose escalation groups were 20.5% and 42.8%, respectively( P = .001). The 2-year local control rates for patients were 35.7% and 76.2%, respectively ( P = .002). When patients were classified into partial metabolic response and no metabolic response, 2-year overall survival rates for patients with partial metabolic response were significantly different in conventional and dose-escalation groups (33.8% vs 78.4%; P = .000). The 2-year overall survival rates for patients with no metabolic response in two groups (8.6% vs 15.1%) did not significantly differ ( P = .917). CONCLUSION: Individualized radiation dose escalation has the potential to improve survival in patients with esophageal carcinoma according to increased rate of complete metabolic response. However, further trials are needed to confirm this and to identify patients who may benefit from dose escalation. PMID- 26834116 TI - Correction of Bowtie-Filter Normalization and Crescent Artifacts for a Clinical CBCT System. AB - PURPOSE: To present our experiences in understanding and minimizing bowtie-filter crescent artifacts and bowtie-filter normalization artifacts in a clinical cone beam computed tomography system. METHODS: Bowtie-filter position and profile variations during gantry rotation were studied. Two previously proposed strategies (A and B) were applied to the clinical cone beam computed tomography system to correct bowtie-filter crescent artifacts. Physical calibration and analytical approaches were used to minimize the norm phantom misalignment and to correct for bowtie-filter normalization artifacts. A combined procedure to reduce bowtie-filter crescent artifacts and bowtie-filter normalization artifacts was proposed and tested on a norm phantom, CatPhan, and a patient and evaluated using standard deviation of Hounsfield unit along a sampling line. RESULTS: The bowtie filter exhibited not only a translational shift but also an amplitude variation in its projection profile during gantry rotation. Strategy B was better than strategy A slightly in minimizing bowtie-filter crescent artifacts, possibly because it corrected the amplitude variation, suggesting that the amplitude variation plays a role in bowtie-filter crescent artifacts. The physical calibration largely reduced the misalignment-induced bowtie-filter normalization artifacts, and the analytical approach further reduced bowtie-filter normalization artifacts. The combined procedure minimized both bowtie-filter crescent artifacts and bowtie-filter normalization artifacts, with Hounsfield unit standard deviation being 63.2, 45.0, 35.0, and 18.8 Hounsfield unit for the best correction approaches of none, bowtie-filter crescent artifacts, bowtie filter normalization artifacts, and bowtie-filter normalization artifacts + bowtie-filter crescent artifacts, respectively. The combined procedure also demonstrated reduction of bowtie-filter crescent artifacts and bowtie-filter normalization artifacts in a CatPhan and a patient. CONCLUSION: We have developed a step-by-step procedure that can be directly used in clinical cone beam computed tomography systems to minimize both bowtie-filter crescent artifacts and bowtie filter normalization artifacts. PMID- 26834117 TI - Molecular prevalence of Entamoeba histolytica/dispar infection among patients attending four health centres in north-west Ethiopia. AB - The prevalence of amoebiasis is often overestimated owing to its epidemiological overlap with the non-pathogenic Entamoeba dispar To provide evidence for this conjecture, a cross-sectional study was conducted from November 2013 to January 2015. A range of 180-200 ug of semi-solid and formed stools and 200 uL of diarrhoeic stool samples were used for DNA extraction from microscopically E. histolytica/dispar positive samples using the QIAamp(r) DNA Stool Mini Kit according to manufacturers' instructions. Nested PCR targeting 18S ribosomal RNA gene was used. In 422 microscopically positive E. histolytica/dispar stools, molecular prevalence revealed that E. histolytica infestation was present in only 1.7% (95% confidence interval [CI], 0.47-2.93) and E. dispar was found in 42.2% (95% CI, 37.49-46.91), while 56.2% (95% CI, 51.47-60.93) had neither E. histolytica nor E. dispar (P < 0.001). We conclude that infestation with E. histolytica is rarer in our study areas than was previously believed. Hence, accurate differentiation of E. histolytica and E. dispar is crucial. PMID- 26834118 TI - Chronic Spontaneous Urticaria (CSU): Canadian Dermatologists' Perspective. AB - BACKGROUND: Chronic spontaneous urticaria (CSU) is a skin disorder that is said to be "frustrating" and "difficult to treat." It is characterized by recurrent hives for more than 6 weeks, and is further divided into spontaneous or inducible by physical stimuli.(1) To better understand dermatologists' perspective of this disorder, a survey was conducted with Canadian dermatologists. METHODS: A detailed online practice survey was sent to all currently practicing Canadian dermatologists. RESULTS: In all, 80 responses were received (response rate of 20%). Most respondents in Canada had treated patients with CSU (98.4%), with many of the patients having the disease last over 6 months (86.6%). A majority of the patients were female, with 84.1% of the respondents having over 50% of their patients as female. Most patients were over the age of 30 (74.2%). Of dermatologists, 85.7% felt that investigations were unhelpful in diagnosing CSU in a patient. Of respondents, 37.1% were not satisfied with current treatment methods of CSU, and 43.6% somewhat satisfied. Popular therapies included H1 and H2 antihistamines, oral corticosteroids, and montelukast. There were 16.1% of dermatologists who had over 50% of their patients refractory to treatment. CONCLUSIONS: There was a clear demographic preponderance for CSU patients with a majority as female over age 30. Investigations ordered for CSU patients do not seem to be helpful among dermatologists. Satisfaction with current therapies and investigations was quite low among Canadian dermatologists, suggesting new therapies are indicated. PMID- 26834119 TI - Development and Evaluation of a Rosacea Screening Instrument (Rosascreen). AB - BACKGROUND: There are no current instruments to facilitate population screening for rosacea. OBJECTIVE: To develop and evaluate a screening instrument for rosacea applicable for population surveys. METHODS: A rosacea-specific screening instrument (Rosascreen), consisting of a subject-completed questionnaire and screening algorithm, was developed based on current diagnostic criteria for rosacea. Three iterations were pilot tested and refined for clarity and sensitivity in adult outpatients with and without rosacea. RESULTS: Three subject groups were consecutively evaluated with iterations of the questionnaire at each centre (overall N = 121). The final version had a sensitivity of 93% to 100% for key diagnostic criteria, and use of the algorithm had a sensitivity of 100% for detection of rosacea and specificity of 63% to 71%. Most subjects found the questionnaire easy to understand and complete. CONCLUSION: Rosascreen, a subject completed questionnaire and diagnostic algorithm, is a highly sensitive screening instrument that may facilitate estimation of rosacea prevalence in general populations. PMID- 26834120 TI - Rationale and Argument for Subunit Mohs Excision in Nasal Reconstruction. AB - BACKGROUND: Optimal aesthetic results are achieved when nasal defects after Mohs micrographic surgery (MMS) are reconstructed as entire nasal subunits. OBJECTIVE: To illustrate the importance of reconstructing the nose in entire subunits and explore the possibilities of expanding the principles of subunit reconstruction to the concept of subunit Mohs excision. METHODS: An 83-year-old man presented for MMS to excise 3 lesions on the nasal ala. The surgeons elected to excise and reconstruct the entire subunit. RESULTS: Excellent aesthetic and functional results were obtained. CONCLUSION: When a defect greater than 50% of a nasal subunit is encountered during MMS, immediate marginal control excision of the entire subunit can be performed with subsequent reconstruction. This technique ultimately has the potential to deliver a more aesthetically pleasing outcome and should be, at the very least, considered by all Mohs surgeons. PMID- 26834121 TI - The Just-Meaningful Difference in Speech-to-Noise Ratio. AB - The speech-to-noise ratio (SNR) in an environment plays a vital role in speech communication for both normal-hearing (NH) and hearing-impaired (HI) listeners. While hearing-assistance devices attempt to deliver as favorable an SNR as possible, there may be discrepancies between noticeable and meaningful improvements in SNR. Furthermore, it is not clear how much of an SNR improvement is necessary to induce intervention-seeking behavior. Here, we report on a series of experiments examining the just-meaningful difference (JMD) in SNR. All experiments used sentences in same-spectrum noise, with two intervals on each trial mimicking examples of pre- and post-benefit situations. Different groups of NH and HI adults were asked (a) to rate how much better or worse the change in SNR was in a number of paired examples, (b) if they would swap the worse for the better SNR (e.g., their current device for another), or (c) if they would be willing to go to the clinic for the given increase in SNR. The mean SNR JMD based on better or worse ratings (one arbitrary unit) was similar to the just noticeable difference, approximately 3 dB. However, the mean SNR JMD for the more clinically relevant tasks-willingness (at least 50% of the time) to swap devices or attend the clinic for a change in SNR--was 6 to 8 dB regardless of hearing ability. This SNR JMD of the order of 6 dB provides a new benchmark, indicating the SNR improvement necessary to immediately motivate participants to seek intervention. PMID- 26834122 TI - Harmonic Frequency Lowering: Effects on the Perception of Music Detail and Sound Quality. AB - A novel algorithm for frequency lowering in music was developed and experimentally tested in hearing-impaired listeners. Harmonic frequency lowering (HFL) combines frequency transposition and frequency compression to preserve the harmonic content of music stimuli. Listeners were asked to make judgments regarding detail and sound quality in music stimuli. Stimuli were presented under different signal processing conditions: original, low-pass filtered, HFL, and nonlinear frequency compressed. Results showed that participants reported perceiving the most detail in the HFL condition. In addition, there was no difference in sound quality across conditions. PMID- 26834123 TI - Maternal T-Cell Engraftment Interferes With Human Leukocyte Antigen Typing in Severe Combined Immunodeficiency. AB - OBJECTIVES: To report the laboratory investigation of a case of severe combined immunodeficiency (SCID) with maternal T-cell engraftment, focusing on the interference of human leukocyte antigen (HLA) typing by blood chimerism. METHODS: HLA typing was performed with three different methods, including sequence specific primer (SSP), sequence-specific oligonucleotide, and Sanger sequencing on peripheral blood leukocytes and buccal cells, from a 3-month-old boy and peripheral blood leukocytes from his parents. Short tandem repeat (STR) testing was performed in parallel. RESULTS: HLA typing of the patient's peripheral blood leukocytes using the SSP method demonstrated three different alleles for each of the HLA-B and HLA-C loci, with both maternal alleles present at each locus. Typing results from the patient's buccal cells showed a normal pattern of inheritance for paternal and maternal haplotypes. STR enrichment testing of the patient's CD3+ T lymphocytes and CD15+ myeloid cells confirmed maternal T-cell engraftment, while the myeloid cell profile matched the patient's buccal cells. CONCLUSIONS: Maternal T-cell engraftment may interfere with HLA typing in patients with SCID. Selection of the appropriate typing methods and specimens is critical for accurate HLA typing and immunologic assessment before allogeneic hematopoietic stem cell transplantation. PMID- 26834124 TI - MYC Immunohistochemistry to Identify MYC-Driven B-Cell Lymphomas in Clinical Practice. AB - OBJECTIVES: Immunohistochemistry with anti-MYC antibody (MYC IHC) detects MYC protein in fixed samples of aggressive B-cell lymphomas and, according to the number of positive staining tumor nuclei, facilitates tumor subclassification, predicts underlying MYC rearrangements, and stratifies patient outcome. We aimed to determine the performance of MYC IHC in clinical practice. METHODS: We reviewed MYC IHC performed on control specimens and 256 aggressive B-cell lymphomas and compared clinically reported IHC scores with experts' review. RESULTS: Control tissues showed less than 5% variation in daily IHC staining. Reported and expert IHC scores were well correlated (r = 0.86) with an SD of 14.2%. Reported IHC scores 30% or less and 70% or more were accurate (94.5%) compared with experts in categorizing tumors as "MYC IHC-Low" and "MYC IHC-High," respectively, but scores 40% to 60% were not (60.3%). The mean IHC score among lymphomas with MYC rearrangements was 80%, but with a large range of scores (20% 100%). There was no statistically significant association between IHC score and MYC copy number. CONCLUSIONS: Under optimal conditions, clinically reported MYC IHC scores are concordant with expert scores within 15%. MYC IHC does not capture all B-cell lymphomas with MYC rearrangements, however. MYC IHC and MYC fluorescence in situ hybridization are both recommended to identify MYC-driven B cell lymphomas. PMID- 26834125 TI - Oligoclonal Bands of Immunoglobulins in Serum Leading to Diagnosis of Human Immunodeficiency Virus 1 Infection. AB - OBJECTIVES: To present a unique case where detection of oligoclonal bands in serum led to the diagnosis of human immunodeficiency virus (HIV) infection. METHODS: A 64-year-old man treated for hypertension for 11 years had laboratory tests ordered by his primary care physician, including serum protein electrophoresis (SPE) and serum immunofixation electrophoresis. RESULTS: The total protein serum protein concentration was elevated at 9.6 g/dL. The SPE showed an oligoclonal pattern of multiple discrete bands in the gamma region; the concentration of one band was approximately 1 g/dL and that of two bands was approximately 0.5 g/dL each, with multiple smaller overlapping bands at approximately 0.1 g/dL each. All fractions by SPE were within reference intervals except for the gamma fraction, which was elevated at 3.4 g/dL. The IFE demonstrated that this oligoclonal pattern was a mixture of multiple bands of immunoglobulin G (IgG)-lambda and IgG-kappa. The patient's HIV-1 antibody screen and HIV-1 Western blot were positive on three subsequent visits with strongly positive HIV-1 antibody index values of more than 50 (cutoff value of 1.0 for reactivity). CONCLUSIONS: The etiology of HIV-associated clonal immunoglobulin bands is hypothesized to result from chronic antigenic stimulation leading to B cell hyperplasia. In this regard, hypergammaglobulinemia is a well-known consequence of HIV infection due to B-cell activation, associated with paraproteins, and can be seen at any stage of the disease. PMID- 26834126 TI - Automated Nucleated RBC Measurement Using the Sysmex XE-5000 Hematology Analyzer: Frequency and Clinical Significance of the Nucleated RBCs. AB - OBJECTIVES: We validated the automatic nucleated RBC (nRBC) count on a Sysmex XE 5000 hematology analyzer (Sysmex Corporation, Kobe, Japan) and then evaluated the frequency of nRBCs in our patient population. METHODS: We correlated automated nRBC enumeration by the Sysmex XE-5000 hematology analyzer on 463 peripheral blood (PB) samples with the manual nRBC count. Results from 360,504 consecutive blood samples were reviewed to determine the frequency of nRBCs in various patient populations in our hospital. RESULTS: There was a strong correlation between the automated and manual nRBC count (Pearson's r = 0.97). Frequency of nRBCs varied in different patient populations and was significantly higher in the presence of other morphology flags or abnormal CBC parameters. Low-level nRBCs (0.2%-1.3%) were detected in 0.5% of samples with otherwise normal parameters. CONCLUSIONS: The automated method offers many advantages for high-throughput laboratories, including faster turnaround time, labor savings, and high reliability. Automated nRBC measurement allowed us to recognize a group of individuals who have low-level circulating nRBCs with otherwise normal CBC parameters. Nucleated RBC levels below 1.5% as detected by the automated count may be present in patients without increased erythropoiesis or a pathologic bone marrow process. PMID- 26834127 TI - 2015 Year-End Metrics. PMID- 26834128 TI - Massive Open Online Courses in Dental Education: Two Viewpoints: Viewpoint 1: Massive Open Online Courses Offer Transformative Technology for Dental Education and Viewpoint 2: Massive Open Online Courses Are Not Ready for Primetime. AB - This point/counterpoint article discusses the strengths and weaknesses of incorporating Massive Open Online Courses (MOOCs) into dental education, focusing on whether this relatively new educational modality could impact traditional dental curricula. Viewpoint 1 asserts that MOOCs can be useful in dental education because they offer an opportunity for students to learn through content and assessment that is delivered online. While specific research on MOOCs is limited, some evidence shows that online courses may produce similar learning outcomes to those in face-to-face courses. Given that MOOCs are intended to be open source, there could be opportunities for dental schools with faculty shortages and financial constraints to incorporate these courses into their curricula. In addition to saving money, dental schools could use MOOCs as revenue sources in areas such as continuing education. Viewpoint 2 argues that the hype over MOOCs is subsiding due in part to weaker than expected evidence about their value. Because direct contact between students, instructors, and patients is essential to the dental curriculum, MOOCs have yet to demonstrate their usefulness in replacing more than a subset of didactic courses. Additionally, learning professionalism, a key component of health professions education, is best supported by mentorship that provides significant interpersonal interaction. In spite of the potential of early MOOC ideology, MOOCs in their current form require either further development or altered expectations to significantly impact dental education. PMID- 26834129 TI - Use of High-Definition Audiovisual Technology in a Gross Anatomy Laboratory: Effect on Dental Students' Learning Outcomes and Satisfaction. AB - Laboratory cadaver dissection is essential for three-dimensional understanding of anatomical structures and variability, but there are many challenges to teaching gross anatomy in medical and dental schools, including a lack of available space and qualified anatomy faculty. The aim of this study was to determine the efficacy of high-definition audiovisual educational technology in the gross anatomy laboratory in improving dental students' learning outcomes and satisfaction. Exam scores were compared for two classes of first-year students at one U.S. dental school: 2012-13 (no audiovisual technology) and 2013-14 (audiovisual technology), and section exams were used to compare differences between semesters. Additionally, an online survey was used to assess the satisfaction of students who used the technology. All 284 first-year students in the two years (2012-13 N=144; 2013-14 N=140) participated in the exams. Of the 140 students in the 2013-14 class, 63 completed the survey (45% response rate). The results showed that those students who used the technology had higher scores on the laboratory exams than those who did not use it, and students in the winter semester scored higher (90.17+/-0.56) than in the fall semester (82.10+/-0.68). More than 87% of those surveyed strongly agreed or agreed that the audiovisual devices represented anatomical structures clearly in the gross anatomy laboratory. These students reported an improved experience in learning and understanding anatomical structures, found the laboratory to be less overwhelming, and said they were better able to follow dissection instructions and understand details of anatomical structures with the new technology. Based on these results, the study concluded that the ability to provide the students a clear view of anatomical structures and high-quality imaging had improved their learning experience. PMID- 26834130 TI - Implementation of a Web-Based Patient Simulation Program to Teach Dental Students in Oral Surgery. AB - The aim of this study was to evaluate a web-based simulation of patients (Web-SP) program on learning skills in clinical reasoning and patient evaluation in the oral surgery education of third-year dental students. A secondary aim was to investigate the program's effect on students' learning, knowledge, and attitudes towards virtual patient simulations. Authentic virtual oral surgery patient cases were created at a dental school in Sweden using the Web-SP platform. The Web-SP program was introduced in a two-hour seminar. A 20-minute pre-seminar test (test A) was administered to assess the students' knowledge of oral surgery prior to experiencing the Web-SP program. Ten days after the seminar, another test (test B) was administered to evaluate the increase in oral surgery knowledge as a result of using the program, and an emailed survey of the students was conducted. Of 70 students in the course, 67 (95.7%) agreed to participate in the study and took test A; of these, 59 (88%) took test B. Of the 59 students who took both tests, 28 (42%) completed the survey. The results of the two tests showed a statistically significant increase in knowledge, which was in accordance with the learning goals (p<0.0001). The survey results showed that the students had a positive attitude towards the teaching method. In this study, Web-SP was found to be a valuable tool for teaching clinical reasoning and patient evaluation in an undergraduate oral surgery education setting by improving learning outcomes in comparison with traditional teaching alone. PMID- 26834131 TI - Assessing the Impact of Voice-Over Screen-Captured Presentations Delivered Online on Dental Students' Learning. AB - The traditional lecturing method is still one of the most common forms of delivering content to students in dental education, but innovative learning technologies have the potential to improve the effectiveness and quality of teaching dental students. What challenges instructors is the extent to which these learning tools have a direct impact on student learning outcomes. The aim of this study was to assess the impact of a voice-over screen-captured learning tool by identifying a positive, nil, or negative impact on student learning as well as student engagement (affective, behavioral, and cognitive) when compared to the traditional face-to-face lecture. Extraneous variables thought to impact student learning were controlled by the use of baseline measures as well as random assignment of second-year dental students to one of two teaching conditions: voice-over screen-captured presentation delivered online and the traditional classroom lecture. A total of 28 students enrolled in the preclinical course in endodontics at a Canadian dental school participated in the study, 14 in each of the two teaching conditions. The results showed that, in most cases, the students who experienced the online lecture had somewhat higher posttest scores and perceived satisfaction levels than those in the face-to-face lecture group, but the differences did not achieve statistical significance except for their long-term recognition test scores. This study found that the students had comparable learning outcomes whether they experienced the face-to-face or the online lecture, but that the online lecture had a more positive impact on their long-term learning. The controls for extraneous variables used in this study suggest ways to improve research into the comparative impact of traditional and innovative teaching methods on student learning outcomes. PMID- 26834132 TI - Using Twitter for Teaching and Learning in an Oral and Maxillofacial Radiology Course. AB - The aim of this study was to describe the implementation of one form of social media (Twitter) in an oral radiology course and evaluate dental students' use and perceptions of this technology for teaching and learning. An author-developed questionnaire was used to solicit second-year students' knowledge, use, and perceptions of Twitter for teaching and learning in an oral radiology course at one U.S. dental school. A combination of Likert scales, multiple allowable answers, and an open-ended comment question was employed. The questionnaire was piloted in spring 2010 followed by data collection in spring 2011. Out of 45 students, 40 (88.9%) completed the questionnaire. Of the respondents, 95% reported having not used Twitter prior to their second year of dental school; 55% of them created an account for the course. The top two reasons they gave for creating an account were viewing radiographic examples and staying informed about questions and answers that were posted. The top two reasons they gave for not creating an account were that the content was viewable online without an account and not wanting another online account. The students perceived the Twitter sessions as helpful and reported it improved accessibility to the instructor. The results of this study challenged the assumption that dental students are well versed in all forms of social media, but overall, these students agreed that the use of Twitter had enhanced the learning environment in the radiology course. PMID- 26834133 TI - Influence of Experience and Training on Dental Students' Examination Performance Regarding Panoramic Images. AB - Physician training has greatly benefitted from insights gained in understanding the manner in which experts search medical images for abnormalities. The aims of this study were to compare the search patterns of 30 fourth-year dental students and 15 certified oral and maxillofacial radiologists (OMRs) over panoramic images and to determine the most robust variables for future studies involving image visualization. Eye tracking was used to capture the eye movement patterns of both subject groups when examining 20 panoramic images classified as normal or abnormal. Abnormal images were further subclassified as having an obvious, intermediate, or subtle abnormality. The images were presented in random order to each participant, and data were collected on duration of the participants' observations and total distance tracked, time to first eye fixation, and total duration and numbers of fixations on and off the area of interest (AOI). The results showed that the OMRs covered greater distances than the dental students (p<0.001) for normal images. For images of pathosis, the OMRs required less total time (p<0.001), made fewer eye fixations (p<0.01) with fewer saccades (p<0.001) than the students, and required less time before making the first fixation on the AOI (p<0.01). Furthermore, the OMRs covered less distance (p<0.001) than the dental students for obvious pathoses. For investigations of images of pathosis, time to first fixation is a robust parameter in predicting ability. For images with different levels of subtlety of pathoses, the number of fixations, total time spent, and numbers of revisits are important parameters to analyze when comparing observer groups with different levels of experience. PMID- 26834134 TI - Stress and Academic Performance in Dental Students: The Role of Coping Strategies and Examination-Related Self-Efficacy. AB - Academic stress negatively affects students' performance. However, little is known of the processes that may be involved in this association. This study aimed to analyze how other variables such as coping strategies and exam-related self efficacy could be related to academic stress and performance for dental students. An online survey, including measures of coping strategies, perceived stress, exam related self-efficacy, and academic performance, was completed by undergraduate dental students in Madrid, Spain. Of the 275 students invited to take the survey, 201 participated (response rate 73.6%). Rational coping strategies (problem solving, positive reappraisal, seeking social support) were negatively associated with perceived stress (beta=-0.25, p<0.01), whereas emotional coping strategies (venting negative emotions, negative auto-focus) were linked to increased academic stress (beta=0.34, p<0.01). Moreover, rational and emotional coping strategies were, respectively, positively (beta=0.16, p<0.05) and negatively (beta=-0.22, p<0.01) associated with students' exam-related self-efficacy, and this relation was found to be partially mediated by the students' perceived stress (beta=-0.30, p<0.01). Experiencing higher levels of stress during the examination period was found to be associated with poorer average grades (beta= 0.21, p<0.01), but students' exam-related self-efficacy partially mediated this relation (beta=0.23, p<0.01). Those students who perceived themselves as more efficient in completing examinations reported better grades. Using adequate coping strategies (i.e., rational coping) may help to reduce stress for dental students and, through their effect on exam-related self-efficacy appraisals, contribute to improved academic performance. PMID- 26834135 TI - Does Reflective Learning with Feedback Improve Dental Students' Self-Perceived Competence in Clinical Preparedness? AB - The value of dental students' self-assessment is often debated. The aim of this study was to explore whether reflective learning with feedback enabled dental students to more accurately assess their self-perceived levels of preparedness on dental competencies. Over 16 weeks, all third- and fourth-year students at a dental school in the Republic of Korea took part in clinical rotations that incorporated reflective learning and feedback. Following this educational intervention, they were asked to assess their perceptions of their clinical competence. The results showed that the students reported feeling most confident about performing periodontal treatment (mean 7.1 on a ten-point scale) and least confident about providing orthodontic care (mean 5.6). The fourth-year students reported feeling more confident on all the competencies than the third-year students. Their self-perceived competence in periodontal treatment and oral medicine significantly predicted the instructors' clinical evaluations. This study offered insights into determining if structured reflective learning with effective feedback helps to increase dental students' self-perceived level of clinical preparedness. PMID- 26834136 TI - Learning Shade Differentiation Using Toothguide Trainer and Toothguide Training Box: A Longitudinal Study with Dental Students. AB - The positive training effect achieved with the Toothguide Training Box (TTB) has been demonstrated in previous studies. The aim of this study was to investigate the training effect with the TTB at six and 12 months using standardized color tests. The study involved 101 dental students. The participants were divided into two study groups and one control group. Ten standard color samples were determined under uniform environmental conditions with VITA 3D-Master. The control group (N=30) took the color test after one week. Study group 1 (N=49) took the color test after six months and study group 2 (N=22) at 12 months for the first time by following the TTB curriculum. The control group achieved an average DeltaEt1=0.85. In study group 1, the DeltaEt2 was 2.29, and in study group 2, DeltaEt3=2.25. The results after six and 12 months were highly significant compared to the control group (alpha=0.001). Dependence was determined only with regard to gender. In this study, the TTB quickly led to an improvement in tooth color differentiation among students. After six months, there was a decrease in the training effect. These results suggest that the TTB curriculum should be provided at the end of preclinical training. PMID- 26834144 TI - Diamondback Moth (Lepidoptera: Plutellidae) Exhibits Oviposition and Larval Feeding Preferences Among Crops, Wild plants, and Ornamentals as Host Plants. AB - Diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), is an agricultural pest with high reproductive potential, widespread distribution, and high resistance to different types of insecticides. Although diamondback moth is a common research subject, questions remain regarding its spatial and temporal host plant usage patterns and preferences within agroecosystems. We examined the adult oviposition and larval feeding preferences of the diamondback moth to assess the potential of alternate host plants as either reservoirs or trap crops. Adult females and third and fourth instars were offered multiple plant species within the plant family Brassicaceae to examine contact preferences and larval ingestion rates. Adult oviposition and larval feeding preferences were identical, with garden cress (Lepidium sativum) (L.) highly preferred, followed by wintercress (Barbarea vulgaris) (L.) and black mustard (Brassica nigra) (L.). Ingestion rates varied among tested plants, with the lowest rate on black mustard and highest on aubretia (Aubretia deltoidea) (L.). Highly preferred plant species were determined to be unfavorable for larval growth and potentially lethal to neonates, suggesting their possible use as trap crops. Understanding ovipositional and larval feeding preferences of diamondback moth can also aid in the development of more accurate monitoring and control strategies for this pest. PMID- 26834143 TI - Association of diethylhexyl phthalate with obesity-related markers and body mass change from birth to 3 months of age. AB - BACKGROUND: Several studies have suggested potential links of phthalates to obesity in children and adults. Limited evidence, however, has been available for the relations between diethylhexyl phthalate (DEHP) and obesity-related markers or body mass change in early life. METHODS: 128 healthy pregnant women were recruited and, after delivery, their newborns' first urine and umbilical cord blood samples were collected. We measured urinary levels of two DEHP metabolites, mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). We also measured the levels of leptin, total cholesterol and triglyceride (TG) in cord serum, and used them along with weight, length, head circumference and ponderal index (PI, 100 g/cm(3)) at birth, as obesity-related markers, and estimated the relations between DEHP metabolites and obesity-related markers using generalised linear models. For the evaluation of body mass increase by early life DEHP exposure, body mass index (BMI) z-score change during 3 months after birth by DEHP metabolites in the first urine samples of the newborns were evaluated using logistic regression. RESULTS: DEHP exposure was associated with decrease of PI and increase of TG (PI, beta=-0.11, p=0.070 and TG, beta=0.14, p=0.027), especially for boys (PI, beta=-0.13, p=0.021; and TG, beta=0.19, p=0.025). Moreover, DEHP exposure was positively associated with body mass increase during 3 months after birth (change of BMI z-scores, OR=4.35, p=0.025). CONCLUSIONS: Our findings suggest that DEHP exposure may affect body mass change in early life through changes of obesity-related markers. PMID- 26834145 TI - Identification of an RNA-binding protein that is phosphorylated by PTH and potentially mediates PTH-induced destabilization of Npt2a mRNA. AB - Parathyroid hormone (PTH) is a key regulator of the expression and function of the type IIa sodium-phosphate cotransporter (Npt2a), the protein responsible for regulated renal phosphate reabsorption. We previously showed that PTH induces rapid decay of Npt2a mRNA through posttranscriptional mechanisms. We hypothesized that PTH-induced changes in RNA-binding protein (RBP) activity mediate the degradation of Npt2a mRNA. To address this aim, we treated opossum kidney (OK) cells, a PTH-sensitive proximal tubule cell culture model, with 100 nM PTH for 30 min and 2 h, followed by mass spectrometry characterization of the PTH-stimulated phosphoproteome. We identified 1,182 proteins differentially phosphorylated in response to PTH, including 68 RBPs. Preliminary analysis identified a phospho RBP, hnRNPK-homology-type-splicing regulatory protein (KSRP), with predicted binding sites for the 3'-untranslated region (UTR) of Npt2a mRNA. Western blot analysis confirmed expression of KSRP in OK cells and showed PTH-dependent translocation to the nucleus. Immunoprecipitation of KSRP from control and PTH treated cells followed by RNA isolation and RT-quantitative PCR analysis identified Npt2a mRNA from both control and PTH-treated KSRP pulldowns. Knockdown of KSRP followed by PTH treatment showed that KSRP is required for mediating PTH stimulated reduction in sodium/hydrogen exchanger 3 mRNA, but not Npt2a mRNA. We conclude that 1) PTH is a major regulator of both transcription and translation, and 2) KSRP binds Npt2a mRNA but its role in PTH regulation of Npt2a mRNA is not clear. PMID- 26834146 TI - Attitudes Toward Domestic Violence and Corporal Punishment Among Former Soviet Union Immigrants in Israel. AB - The study regards attitudes of Russian immigrants in Israel toward wife abuse and corporal punishment. The sample consisted of 1,028 participants, based on a multistage cluster sampling. The study used a questionnaire related to immigration, acculturation, and attitudinal issues. The findings indicate a dual causal model, in which corporal punishment attitudes contribute to wife abuse attitudes and vice versa. However, the effect of attitudes supporting corporal punishment was stronger than the effect of wife abuse attitudes, indicating that the attitudinal system as a precursor of violent behavior is already merging the two types of violence. PMID- 26834142 TI - Epigenetics and Human Disease. AB - Genetic causes for human disorders are being discovered at an unprecedented pace. A growing subclass of disease-causing mutations involves changes in the epigenome or in the abundance and activity of proteins that regulate chromatin structure. This article focuses on research that has uncovered human diseases that stem from such epigenetic deregulation. Disease may be caused by direct changes in epigenetic marks, such as DNA methylation, commonly found to affect imprinted gene regulation. Also described are disease-causing genetic mutations in epigenetic modifiers that either affect chromatin in trans or have a cis effect in altering chromatin configuration. PMID- 26834148 TI - Exploring the Relationship Between Gender Violence and State Failure: A Cross National Comparison. AB - The concept of state failure has only recently emerged in the political science and legal literature. Although state failure has been used to predict violent conflicts, and all citizens are affected by violence in failed/fragile states, women are especially at risk. Using data from the WomanStats project, this study's findings reveal that the physical security of women is lower in failed/fragile states compared with more sustainable nations. The characteristics of failed states that increase the likelihood of various forms of violence against women are identified, including high levels of militarization, countries with neighboring states at war, and massive movement of refugees. PMID- 26834147 TI - Preliminary Validation of the Sex Trafficking Attitudes Scale. AB - This study presents the Sex Trafficking Attitudes Scale (STAS), assessing cognitive, behavioral, and affective attitudes toward the sex trafficking of women and girls. Across two studies, exploratory and confirmatory factor analyses revealed and confirmed six subscales: (a) Knowledge About Sex Trafficking, (b) Awareness of Sex Trafficking, (c) Attitudes Toward Ability to Leave Sex Trafficking, (d) Attitudes Toward Helping Survivors, (e) Empathic Reactions Toward Sex Trafficking, and (f) Efficacy to Reduce Sex Trafficking. Results showed support for convergent validity as the subscales were associated with related measures. The STAS holds promise to expand research and inform efforts to support trafficking survivors. PMID- 26834149 TI - Gender Problems in the Practice of Professional Interpreters Assisting Migrant Women in Australia: A Theoretical Case for Feminist Education. AB - Professional interpreters in Australia have little opportunity to undertake education on issues of violence against women. This article observes a lack of awareness of gender violence-related issues among community interpreters. It then notes examples of gender-related problems arising in the work of interpreters assisting migrant women. It repeats Maree Pardy's call for interpreter education, but diverges from her 1995 work by explicitly recommending this education be informed by feminist principles. It observes that, although community interpreters are key to migrant women accessing social services in Australia, the profession resists calls for specialized education. This resistance occurs in a country that is recognized internationally for its progressive public service interpreting policies. We question why this is the case, and suggest that adherence to a peculiarly superficial notion of "impartiality" dulls the profession's responsiveness to the reality of male violence. We draw on government and non-governmental organization (NGO) reports, as well as interpreting scholarship using a gender lens, to theorize the need for feminist education of professional community interpreters. PMID- 26834150 TI - Models of Invisibility: Rendering Domestic and Other Gendered Violence Visible to Students Through Clinical Law Teaching. AB - The proliferation of university courses about domestic violence includes clinical courses in law schools in which students represent victims in their legal cases. This essay advocates for a broader approach to teaching about the problem. Using examples from their clinic cases, the authors show how teachers can overcome pedagogical challenges and render domestic and other forms of gendered violence, including state and community violence, more visible to students by intentionally raising and placing it within larger frameworks of structural inequality. In this way, students learn to identify and address gendered violence even when it is not the presenting problem. PMID- 26834151 TI - Domestic Violence and Social Justice: A Structural Intersectional Framework for Teaching About Domestic Violence. AB - My Domestic Violence and Social Justice law school course is organized around a structural intersectional framework to encourage students to recognize how structural inequalities inform the types of abuse perpetrated, individual and community responses to abuse, meanings that a victim ascribes to abuse, and factors that increase the risk of abuse. The course challenges the dominant neoliberal ideology focus on individual responsibility that eclipses shared responsibility. The course combines experiential exercises, a presentation by members of a community-based survivor organization, discussion of a hypothetical case with a legal practitioner, and court observation to help students apply theoretical insights to practical issues of individual representation and policy making. PMID- 26834152 TI - Teaching Lawyering With Heart in the George Washington University Law School Domestic Violence Project. AB - The Domestic Violence Project (DVP) began as an experiment but has become my favorite model for teaching law students about domestic violence work. The heart of the course is its emphasis on developing awareness of and compassion for the personally and emotionally challenging dimensions of domestic violence work. I achieve this (i) through an intensive and personal dialogue with students through written journals and responses; (ii) by inviting students to consider creative expression for their final project, and (iii) by teaching students about vicarious trauma and encouraging their understanding of it in themselves and other system players. Students seem to experience this course as an oasis of holistic professional and personal growth within the often dispiriting experience of law school. PMID- 26834153 TI - Teaching Domestic Violence in the New Millennium: Intersectionality as a Framework for Social Change. AB - This article describes an intersectional approach to teaching about domestic violence (DV), which aims to empower students as critical thinkers and agents of change by merging theory, service learning, self-reflection, and activism. Three intersectional strategies and techniques for teaching about DV are discussed: promoting difference-consciousness, complicating gender-only power frameworks, and organizing for change. The author argues that to empower future generations to end violence, educators should put intersectionality into action through their use of scholarship, teaching methods, and pedagogical authority. Finally, the benefits and challenges of intersectional pedagogy for social justice education are considered. PMID- 26834154 TI - RAG-mediated DNA double-strand breaks activate a cell type-specific checkpoint to inhibit pre-B cell receptor signals. AB - DNA double-strand breaks (DSBs) activate a canonical DNA damage response, including highly conserved cell cycle checkpoint pathways that prevent cells with DSBs from progressing through the cell cycle. In developing B cells, pre-B cell receptor (pre-BCR) signals initiate immunoglobulin light (Igl) chain gene assembly, leading to RAG-mediated DNA DSBs. The pre-BCR also promotes cell cycle entry, which could cause aberrant DSB repair and genome instability in pre-B cells. Here, we show that RAG DSBs inhibit pre-BCR signals through the ATM- and NF-kappaB2-dependent induction of SPIC, a hematopoietic-specific transcriptional repressor. SPIC inhibits expression of the SYK tyrosine kinase and BLNK adaptor, resulting in suppression of pre-BCR signaling. This regulatory circuit prevents the pre-BCR from inducing additional Igl chain gene rearrangements and driving pre-B cells with RAG DSBs into cycle. We propose that pre-B cells toggle between pre-BCR signals and a RAG DSB-dependent checkpoint to maintain genome stability while iteratively assembling Igl chain genes. PMID- 26834157 TI - Ptch2 loss drives myeloproliferation and myeloproliferative neoplasm progression. AB - JAK2V617F(+) myeloproliferative neoplasms (MPNs) frequently progress into leukemias, but the factors driving this process are not understood. Here, we find excess Hedgehog (HH) ligand secretion and loss of PTCH2 in myeloproliferative disease, which drives canonical and noncanonical HH-signaling. Interestingly, Ptch2(-/-) mice mimic dual pathway activation and develop a MPN-phenotype with leukocytosis (neutrophils and monocytes), strong progenitor and LKS mobilization, splenomegaly, anemia, and loss of lymphoid lineages. HSCs exhibit increased cell cycling with improved stress hematopoiesis after 5-FU treatment, and this results in HSC exhaustion over time. Cytopenias, LKS loss, and mobilization are all caused by loss of Ptch2 in the niche, whereas hematopoietic loss of Ptch2 drives leukocytosis and promotes LKS maintenance and replating capacity in vitro. Ptch2( /-) niche cells show hyperactive noncanonical HH signaling, resulting in reduced production of essential HSC regulators (Scf, Cxcl12, and Jag1) and depletion of osteoblasts. Interestingly, Ptch2 loss in either the niche or in hematopoietic cells dramatically accelerated human JAK2V617F-driven pathogenesis, causing transformation of nonlethal chronic MPNs into aggressive lethal leukemias with >30% blasts in the peripheral blood. Our findings suggest HH ligand inhibitors as possible drug candidates that act on hematopoiesis and the niche to prevent transformation of MPNs into leukemias. PMID- 26834155 TI - miR-23~27~24 clusters control effector T cell differentiation and function. AB - Coordinated repression of gene expression by evolutionarily conserved microRNA (miRNA) clusters and paralogs ensures that miRNAs efficiently exert their biological impact. Combining both loss- and gain-of-function genetic approaches, we show that the miR-23~27~24 clusters regulate multiple aspects of T cell biology, particularly helper T (Th) 2 immunity. Low expression of this miRNA family confers proper effector T cell function at both physiological and pathological settings. Further studies in T cells with exaggerated regulation by individual members of the miR-23~27~24 clusters revealed that miR-24 and miR-27 collaboratively limit Th2 responses through targeting IL-4 and GATA3 in both direct and indirect manners. Intriguingly, although overexpression of the entire miR-23 cluster also negatively impacts other Th lineages, enforced expression of miR-24, in contrast to miR-23 and miR-27, actually promotes the differentiation of Th1, Th17, and induced regulatory T cells, implying that under certain conditions, miRNA families can fine tune the biological effects of their regulation by having individual members antagonize rather than cooperate with each other. Together, our results identify a miRNA family with important immunological roles and suggest that tight regulation of miR-23~27~24 clusters in T cells is required to maintain optimal effector function and to prevent aberrant immune responses. PMID- 26834156 TI - IL-1-induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation. AB - The features that define autoreactive T helper (Th) cell pathogenicity remain obscure. We have previously shown that Th cells require the transcription factor Bhlhe40 to mediate experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Here, using Bhlhe40 reporter mice and analyzing both polyclonal and TCR transgenic Th cells, we found that Bhlhe40 expression was heterogeneous after EAE induction, with Bhlhe40-expressing cells displaying marked production of IFN-gamma, IL-17A, and granulocyte-macrophage colony stimulating factor. In adoptive transfer EAE models, Bhlhe40-deficient Th1 and Th17 cells were both nonencephalitogenic. Pertussis toxin (PTX), a classical co adjuvant for actively induced EAE, promoted IL-1beta production by myeloid cells in the draining lymph node and served as a strong stimulus for Bhlhe40 expression in Th cells. Furthermore, PTX co-adjuvanticity was Bhlhe40 dependent. IL-1beta induced Bhlhe40 expression in polarized Th17 cells, and Bhlhe40-expressing cells exhibited an encephalitogenic transcriptional signature. In vivo, IL-1R signaling was required for full Bhlhe40 expression by Th cells after immunization. Overall, we demonstrate that Bhlhe40 expression identifies encephalitogenic Th cells and defines a PTX-IL-1-Bhlhe40 pathway active in EAE. PMID- 26834159 TI - Contemporary Management of Borderline Resectable and Locally Advanced Unresectable Pancreatic Cancer. AB - Adenocarcinoma of the pancreas remains a highly lethal disease, with less than 5% survival at 5 years. Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC) account for approximately 30% of newly diagnosed cases of PC. The objective of BRPC therapy is to downstage the tumor to allow resection; the objective of LAPC therapy is to control disease and improve survival. There is no consensus on the definitions of BRPC and LAPC, which leads to major limitations in designing clinical trials and evaluating their results. A multimodality approach is always needed to ensure proper utilization and timing of chemotherapy, radiation, and surgery in the management of this disease. Combination chemotherapy regimens (5-fluorouracil, leucovorin, irinotecan, oxaliplatin, and gemcitabine [FOLFIRINOX] and gemcitabine/nab paclitaxel) have improved overall survival in metastatic disease. The role of combination chemotherapy regimens in BRPC and LAPC is an area of active investigation. There is no consensus on the dose, modality, and role of radiation therapy in the treatment of BRPC and LAPC. This article reviews the literature and highlights the areas of controversy regarding management of BRPC and LAPC. IMPLICATIONS FOR PRACTICE: Pancreatic cancer is one of the worst cancers with regard to survival, even at early stages of the disease. This review evaluates all the evidence for the stages in which the cancer is not primarily resectable with surgery, known as borderline resectable or locally advanced unresectable. Recently, advancements in radiation techniques and use of better combination chemotherapies have improved survival and tolerance. There is no consensus on description of stages or treatment sequences (chemotherapy, chemoradiation, radiation), nor on the best chemotherapy regimen. The evidence behind the treatment paradigm for these stages of pancreatic cancer is summarized. PMID- 26834158 TI - Expanding the antimalarial toolkit: Targeting host-parasite interactions. AB - Recent successes in malaria control are threatened by drug-resistant Plasmodium parasites and insecticide-resistant Anopheles mosquitoes, and first generation vaccines offer only partial protection. New research approaches have highlighted host as well as parasite molecules or pathways that could be targeted for interventions. In this study, we discuss host-parasite interactions at the different stages of the Plasmodium life cycle within the mammalian host and the potential for therapeutics that prevent parasite migration, invasion, intracellular growth, or egress from host cells, as well as parasite-induced pathology. PMID- 26834161 TI - How Cancers Escape Immune Destruction and Mechanisms of Action for the New Significantly Active Immune Therapies: Helping Nonimmunologists Decipher Recent Advances. AB - With the Food and Drug Administration and other worldwide regulatory authorities' approval of ipilimumab (Yervoy), sipuleucel-T (Provenge), nivolumab (Opdivo), and pembrolizumab (Keytruda), oncologic therapy has now moved into noncancer cell targets within the immune system. For many nonimmunologists, understanding how these vastly different therapies work to improve survival, like no other therapies have in the past, is a challenge. The present report reviews the normal function of the immune system, how cancers escape the normal immune system, and how these new therapies improve immune system reactions against cancers. IMPLICATIONS FOR PRACTICE: Oncologists have tremendous experience with therapies that target the cancer cells. New biologic agents have been rapidly introduced recently that target not cancer cells, but the patient's immune cells. The mechanisms of action of these immune-based biologic agents are within the host immune system. To understand these new biologic therapies, basic knowledge of normal and abnormal immune function is essential. The present report explains the up-to-date basic immune normal and abnormal function and prepares the oncologist to understand how the new drugs work, why they work, and why there are associated adverse events. PMID- 26834160 TI - Elevation of Urinary 2-Hydroxyglutarate in IDH-Mutant Glioma. AB - BACKGROUND: Recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes, which are frequent in gliomas, result in marked accumulation of the metabolic by-product 2-hydroxyglutarate (2-HG) within tumors. In other malignancies, such as acute myeloid leukemia, presence of IDH mutation is associated with elevated 2-HG levels in serum or urine compartments. Circulating 2-HG in patients with glial malignancies has not been thoroughly investigated. METHODS: In this study, we analyzed 2-HG levels in the serum and urine of a large set of patients with IDH-mutant and IDH-wild-type glioma, and the cerebrospinal fluid (CSF) from a subset of this cohort. RESULTS: We found that 2-HG was elevated in the urine of patients with IDH-mutant versus IDH-wild-type glioma, although no significant differences in 2-HG levels were observed in the serum or the small set of CSF samples obtained. Among patients with IDH-mutant glioma, 2 HG levels did not differ based on the histopathologic grade, genetic subtype (TP53 mutant or 1p/19q codeleted), presence of a canonical (IDH1 R132H) or noncanonical (any other IDH variant) mutation, or treatment type. CONCLUSION: Our finding suggests that urinary 2-HG is increased among patients with IDH-mutant gliomas, and may represent a future surrogate, noninvasive biomarker to aid in diagnosis, prognosis, and management. IMPLICATIONS FOR PRACTICE: Patients with glioma who harbor mutations in isocitrate dehydrogenase genes showed selective elevation of the oncometabolite 2-hydroxyglutarate in the urine. Similar elevations were not identified in the serum or cerebrospinal fluid. 2 Hydroxyglutarate may serve as a useful, noninvasive biomarker to stratify patients newly diagnosed with glioma with regard to prognosis and management. PMID- 26834163 TI - Antidepressant treatment response: 'I want it all, and I want it now!'?. AB - The treatment of depression remains suboptimal, highlighting the need for more effective antidepressants. Traditional drug discovery and development is time consuming and costly, prompting the need for faster translation of novel therapies into practice. But clinical expediency comes at a cost against which potential benefits need to be considered judiciously. PMID- 26834164 TI - A hospital for the mentally ill in the Middle Ages--psychiatry in history. PMID- 26834165 TI - What can psychiatry learn from the Munro Review of Child Protection? AB - The Munro Review of Child Protection approached the problem of child protection from an understanding based upon systems analysis. Risk assessment in psychiatry has similarities to the assessment by social workers of child protection issues. Psychiatry as a profession could learn from the Review, and, in doing so, be supported in recovering and communicating the requirements for good clinical practice. PMID- 26834162 TI - Antibacterials Developed to Target a Single Organism: Mechanisms and Frequencies of Reduced Susceptibility to the Novel Anti-Clostridium difficile Compounds Fidaxomicin and LFF571. AB - Clostridium difficile is the most common cause of antibacterial-associated diarrhea. Clear clinical presentation and rapid diagnostics enable targeted therapy for C. difficile infection (CDI) to start quickly. CDI treatment includes metronidazole and vancomycin (VAN). Despite decades of use for CDI, no clinically meaningful resistance to either agent has emerged. Fidaxomicin (FDX), an RNA polymerase inhibitor, is also approved to treat CDI. Mutants with reduced susceptibility to FDX have been selected in vitro by single and multistep methods. Strains with elevated FDX minimum inhibitory concentrations (MICs) were also identified from FDX-treated patients in clinical trials. LFF571 is an exploratory agent that inhibits EF-Tu. In a proof-of-concept study, LFF571 was safe and effective for treating CDI. Spontaneous mutants with reduced susceptibility to LFF571 were selected in vitro in a single step, but not via serial passage. Although there are several agents in development for treatment of CDI, this review summarizes the frequencies and mechanisms of C. difficile mutants displaying reduced susceptibility to FDX or LFF71. PMID- 26834166 TI - The passing of 'the Prof'. AB - The archetypal professor of the 20th century is a dying breed, and now 'the Prof' truly occupies emeritus status. This article seeks to remember the Profs with fondness and consider some of the processes that led to their extinction. PMID- 26834167 TI - Oral ketamine for the treatment of pain and treatment-resistant depression?. AB - BACKGROUND: Recent studies with intravenous (i.v.) application of ketamine show remarkable but short-term success in patients with MDD. Studies in patients with chronic pain have used different ketamine applications for longer time periods. This experience may be relevant for psychiatric indications. AIMS: To review the literature about the dosing regimen, duration, effects and side-effects of oral, intravenous, intranasal and subcutaneous routes of administration of ketamine for treatment-resistant depression and pain. METHOD: Searches in PubMed with the terms 'oral ketamine', 'depression', 'chronic pain', 'neuropathic pain', 'intravenous ketamine', 'intranasal ketamine' and 'subcutaneous ketamine' yielded 88 articles. We reviewed all papers for information about dosing regimen, number of individuals who received ketamine, number of ketamine days per study, results and side-effects, as well as study quality. RESULTS: Overall, the methodological strength of studies investigating the antidepressant effects of ketamine was considered low, regardless of the route of administration. The doses for depression were in the lower range compared with studies that investigated analgesic use. Studies on pain suggested that oral ketamine may be acceptable for treatment-resistant depression in terms of tolerability and side-effects. CONCLUSIONS: Oral ketamine, given for longer time periods in the described doses, appears to be well tolerated, but few studies have systematically examined the longer-term negative consequences. The short- and longer-term depression outcomes as well as side-effects need to be studied with rigorous randomised controlled trials. PMID- 26834169 TI - Survival in somatoform disorders--in 100 words. PMID- 26834168 TI - Efficacy of selective serotonin reuptake inhibitors and adverse events: meta regression and mediation analysis of placebo-controlled trials. AB - BACKGROUND: It has been suggested that the efficacy of antidepressants has been overestimated in clinical trials owing to unblinding of drug treatments by adverse events. AIMS: To investigate the association between adverse events and the efficacy of selective serotonin reuptake inhibitors (SSRIs). METHOD: The literature was searched to identify randomised, double-blind, placebo-controlled trials of SSRIs in the treatment of major depression. Efficacy outcomes were response to treatment and change in depressive symptoms. Reporting of adverse events was used as an indicator of tolerability. Random effects meta-analyses were used to calculate pooled estimates. Meta-regression analyses were performed to investigate the association between adverse events and efficacy. Potential mediation was investigated with the Baron & Kenny approach. RESULTS: A total of 68 trials (n = 17 646) were included in the analyses. In meta-analysis SSRIs were superior to placebo in terms of efficacy (odds ratio, OR = 1.62, 95% CI 1.51 1.72). More patients allocated to SSRIs reported adverse events than did patients receiving placebo (OR = 1.73, 95% CI 1.58-1.89). Meta-regression analyses did not find an association between adverse events and efficacy (P = 0.439). There was no indication of adverse events mediating the effect of SSRI treatment. CONCLUSIONS: Our results do not support, but also do not unequivocally disprove, the hypothesis that adverse events lead to an overestimation of the effect of SSRIs over placebo. PMID- 26834170 TI - An 18th-century view of demonomania. I: Classification--psychiatry in history. PMID- 26834171 TI - Putative high risk for psychosis should not be considered a disorder. PMID- 26834172 TI - Authors' reply. PMID- 26834173 TI - Childhood environment and intergenerational transmission of depression. PMID- 26834174 TI - Authors' reply. PMID- 26834175 TI - Kaleidoscope. PMID- 26834178 TI - Xylan synthesized by Irregular Xylem 14 (IRX14) maintains the structure of seed coat mucilage in Arabidopsis. AB - During differentiation, the Arabidopsis seed coat epidermal cells synthesize and secrete large quantities of pectinaceous mucilage into the apoplast, which is then released to encapsulate the seed upon imbibition. In this study, we showed that mutation in Irregular Xylem 14 (IRX14) led to a mucilage cohesiveness defect due to a reduced xylan content. Expression of IRX14 was detected specifically in the seed coat epidermal cells, reaching peak expression at 13 days post-anthesis (DPA) when the accumulation of mucilage polysaccharides has ceased. Sectioning of the irx14-1 seed coat revealed no visible structural change in mucilage secretory cell morphology. Although the total amount of mucilage was comparable with the wild type (WT), the partition between water-soluble and adherent layers was significantly altered in irx14-1, with redistribution from the adherent layer to the water-soluble layer. The monosaccharide composition analysis revealed that xylose content was significantly reduced in irx14-1 water-soluble and adherent mucilage compared with the WT. The macromolecular characteristics of the water soluble mucilage were modified in irx14-1 with a loss of the larger polymeric components. In accordance, glycome profiling and dot immunoblotting of seed mucilage using antibodies specific for rhamnogalacturonan I (RG I) and xylan confirmed the ultra-structural alterations in the irx14-1 mucilage. Meanwhile, the crystalline cellulose content was reduced in the irx14-1 mucilage. These results demonstrated that IRX14 was required for the biosynthesis of seed mucilage xylan, which plays an essential role in maintaining mucilage architecture potentially through altering the crystallization and organization of cellulose. PMID- 26834182 TI - The IBD-Cope: A New Instrument for Measuring Coping in Inflammatory Bowel Disease Patients. AB - BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) has a major impact on psychological well-being. How an individual copes with IBD determines quality of life. We aimed to develop a brief, IBD-specific questionnaire to assess coping strategies (IBD-Cope) and to determine its test-retest reliability and validity. METHODS: Twenty IBD coping strategies were initially deemed to have face validity. Participants were recruited from an existing study, specialist outpatient clinics and via email. Distribution analyses were performed before test-retest reliability was determined. Exploratory factor analyses (EFAs) were then performed before cross-sectional validity was tested. RESULTS: The majority of participants in the study samples were female and most had Crohn's disease. All participants were aged between 18 and 65 years. EFA on the initial validation sample produced two components explaining 42% of the variance, and broadly reflected 'good' and 'bad' coping. EFA on the repeat validation sample showed three questions consistently clustering into either good or bad coping strategies. Good and bad coping strategies defined using the IBD-Cope were positively associated with adaptive (r = 0.57, p < 0.01) and maladaptive (r = 0.55, p < 0.01) coping on the Brief Coping Operations Preference Enquiry (Brief COPE), respectively. CONCLUSIONS: The IBD-Cope is a concise IBD-specific coping strategy questionnaire with demonstrated reliability and validity. The IBD-Cope subscales are moderately correlated with adaptive and maladaptive subscales of the Brief COPE. Prospective studies are required to determine whether the 6 questions represented in the IBD-Cope accurately identify IBD patients who may benefit from interventions to improve coping strategies. PMID- 26834179 TI - Interactions between 2-Cys peroxiredoxins and ascorbate in autophagosome formation during the heat stress response in Solanum lycopersicum. AB - 2-Cys peroxiredoxins (2-CPs) function in the removal of hydrogen peroxide and lipid peroxides but their precise roles in the induction of autophagy have not been characterized. Here we show that heat stress, which is known to induce oxidative stress, leads to the simultaneous accumulation of transcripts encoding 2-CPs and autophagy proteins, as well as autophagosomes, in tomato (Solanum lycopersicum) plants. Virus-induced gene silencing of the tomato peroxiredoxin genes 2-CP1, 2-CP2, and 2-CP1/2 resulted in an increased sensitivity of tomato plants to heat stress. Silencing 2-CP2 or 2-CP1/2 increased the levels of transcripts associated with ascorbate biosynthesis but had no effect on the glutathione pool in the absence of stress. However, the heat-induced accumulation of transcripts associated with the water-water cycle was compromised by the loss of 2-CP1/2 functions. The transcript levels of autophagy-related genes ATG5 and ATG7 were higher in plants with impaired 2-CP1/2 functions, and the formation of autophagosomes increased, together with an accumulation of oxidized and insoluble proteins. Silencing of ATG5 or ATG7 increased the levels of 2-CP transcripts and protein but decreased heat stress tolerance. These results demonstrate that 2-CPs fulfil a pivotal role in heat stress tolerance in tomato, via interactions with ascorbate-dependent pathways and autophagy. PMID- 26834183 TI - Higher cough flow is associated with lower risk of pneumonia in acute stroke. AB - There is little available evidence to demonstrate how cough strength mediates the risk of aspiration-related pneumonia in acute stroke. Our secondary analysis of trial data indicates that risk of pneumonia reduces with increasing peak cough flow (PCF) of voluntary cough (OR 0.994 for each 1 L/min increase in PCF, 95% CI 0.988 to 1.0, p=0.035); and to a lesser degree with increasing PCF of reflex cough (OR 0.998 for each 1 L/min increase in PCF, 95% CI 0.992 to 1.004, p=0.475). These data serve hypothesis generation. Further studies are needed to confirm these findings and validate their clinical utility. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN40298220 (post-results). PMID- 26834184 TI - Gastro-oesophageal reflux and worse asthma control in obese children: a case of symptom misattribution? AB - BACKGROUND: Obese children for unknown reasons report greater asthma symptoms. Asthma and obesity both independently associate with gastro-oesophageal reflux symptoms (GORS). Determining if obesity affects the link between GORS and asthma will help elucidate the obese-asthma phenotype. OBJECTIVE: Extend our previous work to determine the degree of associations between the GORS and asthma phenotype. METHODS: We conducted a cross-sectional study of lean (20%-65% body mass index, BMI) and obese (>=95% BMI) children aged 10-17 years old with persistent, early-onset asthma. Participants contributed demographics, GORS and asthma questionnaires and lung function data. We determined associations between weight status, GORS and asthma outcomes using multivariable linear and logistic regression. Findings were replicated in a second well-characterised cohort of asthmatic children. RESULTS: Obese children had seven times higher odds of reporting multiple GORS (OR=7.7, 95% CI 1.9 to 31.0, interaction p value=.004). Asthma symptoms were closely associated with GORS scores in obese patients (r=0.815, p<0.0001) but not in leans (r=0.291, p=0.200; interaction p value=0.003). Higher GORS scores associated with higher FEV1-per cent predicted (p=0.003), lower airway resistance (R10, p=0.025), improved airway reactance (X10, p=0.005) but significantly worse asthma control (Asthma Control Questionnaire, p=0.007). A significant but weaker association between GORS and asthma symptoms was seen in leans compared with obese in the replicate cohort. CONCLUSION: GORS are more likely to associate with asthma symptoms in obese children. Better lung function among children reporting gastro-oesophageal reflux and asthma symptoms suggests that misattribution of GORS to asthma may be a contributing mechanism to excess asthma symptoms in obese children. PMID- 26834186 TI - Development and Characterization of MIR604 Resistance in a Western Corn Rootworm Population (Coleoptera: Chrysomelidae). AB - mCry3A is one of only four proteins licensed for commercial use in Diabrotica control. Utilizing a colony of western corn rootworm, Diabrotica virgifera virgifera LeConte, selected for resistance to mCry3A, we evaluated how mCry3A resistance was inherited and whether fitness costs were associated with mCry3A resistance. Reciprocal crosses between a selected colony and a control colony were performed; resulting progeny along with parent colonies were evaluated in dose toxicity assays, greenhouse assays, and seedling assays. Dose toxicity assay results were inconclusive, as the highest dose of protein tested did not produce sufficient mortality for accurate LC50 calculation. In whole-plant greenhouse assays on mCry3A-expressing corn, larval relative survival of the selected female * control male reciprocal cross was similar to that of the selected colony, while that of the control female * selected male was intermediate between the mCry3 selected colony and the control colony. However, when adult relative survival in whole-plant greenhouse assays was examined, no significant difference between the reciprocal crosses and the two parent colonies was detected. Heritability calculations based on both larval (0.66) and adult (1.03) survival data indicate that resistance to mCry3A is not inherited in a recessive manner. The selected colony was removed from selection pressure and evaluated after three or eight generations of removal. At three generations of removal from selection, a slight decrease in larval relative survival was detected compared with the selected colony. At eight generations of removal from selection, larval relative survival was comparable with that of the selected colony. PMID- 26834185 TI - Are there three main subgroups within the patellofemoral pain population? A detailed characterisation study of 127 patients to help develop targeted intervention (TIPPs). AB - BACKGROUND: Current multimodal approaches for the management of non-specific patellofemoral pain are not optimal, however, targeted intervention for subgroups could improve patient outcomes. This study explores whether subgrouping of non specific patellofemoral pain patients, using a series of low cost simple clinical tests, is possible. METHOD: The exclusivity and clinical importance of potential subgroups was assessed by applying a priori test thresholds (1 SD) from seven clinical tests in a sample of adult patients with non-specific patellofemoral pain. Hierarchical clustering and latent profile analysis, were used to gain additional insights into subgroups using data from the same clinical tests. RESULTS: 130 participants were recruited, 127 had complete data: 84 (66%) female, mean age 26 years (SD 5.7) and mean body mass index 25.4 (SD 5.83), median (IQR) time between onset of pain and assessment was 24 (7-60) months. Potential subgroups defined by the a priori test thresholds were not mutually exclusive and patients frequently fell into multiple subgroups. Using hierarchical clustering and latent profile analysis three subgroups were identified using 6 of the 7 clinical tests. These subgroups were given the following nomenclature: (1) 'strong', (2) 'weak and tighter' and (3) 'weak and pronated foot'. CONCLUSIONS: We conclude that three subgroups of patellofemoral patients may exist based on the results of six clinical tests which are feasible to perform in routine clinical practice. Further research is needed to validate these findings in other data sets and, if supported by external validation, to see if targeted interventions for these subgroups improve patient outcomes. PMID- 26834187 TI - Honey Bees Avoiding Ant Harassment at Flowers Using Scent Cues. AB - Pollinators require resources throughout the year to maintain healthy populations. Along the urban-natural interface, floral resource availability may be limited especially when the system experiences extreme drought and fire threats. In such areas, succulents, such as Aloe spp., are commonly planted to serve as functional drought-tolerant, fire-protective landscaping, which can also support pollinator populations. However, access to this resource may be restricted by competition from other floral foragers, including invasive pests. We measured free-foraging honey bee (Apis mellifera L.) visitation rate and visitation duration to aloe flowers with and without Argentine ants (Linepithema humile (Mayr)) in a drought-stressed environment and found that bees actively avoided foraging on the ant-occupied flowers. To determine the mechanisms of avoidance, our subsequent experiments assessed visitation in the absence of ants and compared aloe flowers treated with ant pheromone to unmanipulated flowers lacking ant pheromone. Bees approached all flowers equally, but accepted flowers without ants at a higher rate than flowers with ants. Visitation duration also increased twofold on ant-excluded flowers, which suggests that Argentine ants may limit resource acquisition by bees. Honey bees similarly avoided flowers with Argentine ant pheromone and preferentially visited unmanipulated flowers at threefold higher rate. This study demonstrates that honey bees avoid foraging on floral resources with invasive Argentine ants and that bees use ant odors to avoid ant-occupied flowers. Resource limitation by this invasive pest ant may have serious implication for sustaining healthy pollinator populations at the urban-natural interface. PMID- 26834188 TI - Mistletoe (Viscum album) infestation in the Scots pine stimulates drought dependent oxidative damage in summer. AB - This study sought to contribute to the understanding of the detrimental effect of the mistletoe (Viscum albumL.), a hemiparasitic plant, on the mortality of the Scots pine (Pinus sylvestrisL.). Fieldwork was conducted in the town of Kelkit (Gumushane province, Turkey) from April to October in 2013. Pine needles of similar ages were removed from the branches of mistletoe-infested and noninfested Scots pine plants, then transported to the laboratory and used as research materials. The effects of the mistletoe on the Scots pine during infestation were evaluated by determining the levels of water, electrolyte leakage (EL), malondialdehyde (MDA, being a product of lipid peroxidation) and reactive oxygen species (ROS) such as superoxide anion (O2 (-*)), hydrogen peroxide (H2O2) and hydroxyl radical ((*)OH). In addition, the activities of antioxidative enzymes such as superoxide dismutase (SOD), catalase (CAT) and peroxidase (POX) were measured in the same samples. The highest level of drought stress was found in summer (especially in August) as a result of the lowest water content in the soil and the highest average temperature occurring in these months. The drought stress induced by mistletoe infestation caused a regular decrease in water content, while it increased the levels of EL, MDA and ROS (H2O2, O2 (-*)and(*)OH). The infestation also stimulated the activities of CAT and POX, with the exception of SOD. On the other hand, in August, when the drought conditions were the harshest, the levels of EL and MDA, which are two of the most important indicator parameters for oxidative stress, as well as the levels of H2O2and(*)OH, which are two of the ROS leading to oxidative stress, reached the highest values in both infested and noninfested needles, whereas the O2 (-*)level decreased. For the same period and needles, CAT activity increased, while SOD activity decreased. Peroxidase activity, however, did not exhibit a significant change. Our findings indicate that the increased mortality of the Scots pine may result from the mistletoe-induced very severe drought stress, and that the increase in the capacity of antioxidative enzyme system does not protect the plant against oxidative stress in dry summer seasons. PMID- 26834189 TI - Heart transplantations in adults with congenital heart disease: new frontiers. PMID- 26834190 TI - Women's interest in a personal breast cancer risk assessment and lifestyle advice at NHS mammography screening. AB - Background: Although mortality from breast cancer is declining, incidence continues to increase and is often detected at routine NHS screening. Most middle aged and older women in England attend for screening every 3 years. Assessing their personal breast cancer risk and providing preventative lifestyle advice could help to further reduce breast cancer incidence. Methods: A cross-sectional, self-complete postal survey measured attendees' interest in having a personal risk assessment, expected impact on screening attendance, knowledge of associations between lifestyle and breast cancer and preferred ways of accessing preventative lifestyle advice. Results: A total of 1803/4948 (36.4%) completed questionnaires were returned. Most participants (93.7%) expressed interest in a personal risk assessment and 95% (1713/1803) believed it would make no difference or encourage re-attendance. Two-thirds (1208/1803) associated lifestyle with breast cancer, but many were unaware of specific risks such as weight gain, obesity, alcohol consumption and physical inactivity. NHS sourced advice was expected to be more credible than other sources, and booklets, brief counselling or an interactive website were most preferred for accessing this. Conclusions: Attendees appear to welcome an intervention that would facilitate more proactive clinical and lifestyle prevention and address critical research gaps in breast cancer prevention and early detection. PMID- 26834191 TI - Impact of combined lifestyle factors on metabolic syndrome in Korean men. AB - Background: The purpose of this study was to determine the relationship between combined poor lifestyle factors and metabolic syndrome (MetS) in Korean men. Methods: Data from the Korean National Health and Nutrition Examination Survey 2010 were classified according to the number and combination patterns of poor lifestyle factors, namely, current smoking, high-risk alcohol use, low physical activity and poor dietary habits. We analyzed the association between the combined poor lifestyle factors and MetS. The definition of MetS was based on the joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention in 2009. Results: A total of 1408 men aged 20-75 were included in this study. Approximately one-third of the 30-49 age group had >=3 combined poor lifestyle factors. Compared with those with no poor lifestyle factors, the ORs for MetS were 3.57 (95% CI 1.16-11.02), 3.62 (95% CI 1.18-11.08) and 6.31 (95% CI 2.08-19.26) in subjects with one, two and three or more poor lifestyle factors, respectively. When current smoking, high-risk alcohol use and low physical activity were concurrently present, the ORs for MetS, hyperglycemia, and hypertriglyceridemia were 14.32 (95% CI 3.64-56.30), 4.49 (95% CI 1.62 12.40), and 5.07 (95% CI 2.18-11.81), respectively. Conclusions: Comprehensive lifestyle modifications need to be stressed in public health programs. PMID- 26834192 TI - Sleep duration and adiposity in early adolescents: response. PMID- 26834193 TI - Sleep duration and adiposity in early adolescents. PMID- 26834194 TI - Experiences of accessing obesity surgery on the NHS: a qualitative study. AB - Background: Although surgical treatment is recommended for morbid obesity where other interventions have failed, there is evidence that access to NHS surgery is heavily rationed. This study aimed to investigate how patients experienced accessing referrals for obesity surgery. Methods: Data collection was undertaken using in-depth interviews with patients and clinicians working in a specialist secondary care facility, and analysis took a constant comparative approach. Results: Twenty-two participants with morbid obesity were followed up for a period of up to 3 years. All participants had made multiple attempts to lose weight prior to consulting their GPs yet felt this was rarely acknowledged by clinicians. Participants were frustrated when they received insufficient support to comply with primary care interventions, and when it came to obtaining a referral to secondary care, most had to raise this issue with GPs themselves. Conclusions: There is an urgent need for interventions for morbid obesity in primary care that are accessible to patients to facilitate weight loss and prevent weight re-gain. For those at very high weights, better integration between primary and secondary care is required to ensure appropriate and timely referral for those who need assessment for surgery. PMID- 26834196 TI - Treatment of Hepatic Cystic Echinococcosis in Patients from the Southeastern Rhodope Region of Bulgaria in 2004-2013: Comparison of Current Practices with Expert Recommendations. AB - Cystic echinococcosis (CE) is a clinically complex chronic parasitic disease, management options for which include surgery, percutaneous treatments, and treatment with albendazole (ABZ) for active cysts, and the "Watch-and-Wait" approach for uncomplicated, inactive cysts. We examined, retrospectively, the clinical management of 334 patients with hepatic CE from the southeastern Rhodope region of Bulgaria between 2004 and 2013. Cysts were reclassified according to the World Health Organization Informal Working Group on Echinococcosis (WHO-IWGE) on the basis of ultrasound reports and images. The majority (62.3%) of uncomplicated cysts were CE1, 66% of which were treated surgically. Of all interventions, 5% were performed on inactive uncomplicated CE4-CE5 cysts. About half (47.6%) of these cysts were therefore treated inappropriately, exposing patients to unnecessary treatment-related risks and the health system to unnecessary costs. No management change was observed after the publication of the WHO-IWGE Expert Consensus recommendations in 2010. In Bulgaria, ABZ is still used in interrupted cycles as this is reimbursed, and peri-interventional chemoprophylaxis was not administered in the majority of surgical patients. Efforts are needed to introduce the WHO-IWGE classification and management recommendations and to encourage reception of state-of-the-art practices by public health regulatory bodies to improve patient quality of care and optimization of health resources. PMID- 26834195 TI - Eave Screening and Push-Pull Tactics to Reduce House Entry by Vectors of Malaria. AB - Long-lasting insecticidal nets and indoor residual spraying have contributed to a decline in malaria over the last decade, but progress is threatened by the development of physiological and behavioral resistance of mosquitoes against insecticides. Acknowledging the need for alternative vector control tools, we quantified the effects of eave screening in combination with a push-pull system based on the simultaneous use of a repellent (push) and attractant-baited traps (pull). Field experiments in western Kenya showed that eave screening, whether used in combination with an attractant-baited trap or not, was highly effective in reducing house entry by malaria mosquitoes. The magnitude of the effect varied for different mosquito species and between two experiments, but the reduction in house entry was always considerable (between 61% and 99%). The use of outdoor, attractant-baited traps alone did not have a significant impact on mosquito house entry but the high number of mosquitoes trapped outdoors indicates that attractant-baited traps could be used for removal trapping, which would enhance outdoor as well as indoor protection against mosquito bites. As eave screening was effective by itself, addition of a repellent was of limited value. Nevertheless, repellents may play a role in reducing outdoor malaria transmission in the peridomestic area. PMID- 26834197 TI - Taenia solium Taeniasis and Cysticercosis in Southeast Asia. AB - Human taeniasis/cysticercosis caused by the pork tapeworm Taenia solium has been identified as a potentially eradicable disease by the International Task Force for Disease Eradication of the World Health Organization. In southeast Asia, T. solium taeniasis/cysticercosis is considered one of the major neglected tropical diseases afflicting the region. In the last few decades, a considerable effort has been invested toward establishing the epidemiology and burden of disease in several southeast Asian countries. Moreover, further evidence is emerging as to understanding the dynamics of disease transmission and cultural, political, and socioeconomic factors influencing the success of control and eradication efforts within the region. However, despite major collaborations by several champion groups, advances have been slow and little remains known about the complete epidemiology of taeniasis/cysticercosis and the barriers to programmatic success. This review article aims to address the above issues with a further focus on the challenges to control and eradicate taeniasis/cysticercosis within the southeast Asia region. PMID- 26834198 TI - Severe Cutaneous Leishmaniasis in a Human Immunodeficiency Virus Patient Coinfected with Leishmania braziliensis and Its Endosymbiotic Virus. AB - Leishmania parasites cause a broad range of disease, with cutaneous afflictions being, by far, the most prevalent. Variations in disease severity and symptomatic spectrum are mostly associated to parasite species. One risk factor for the severity and emergence of leishmaniasis is immunosuppression, usually arising by coinfection of the patient with human immunodeficiency virus (HIV). Interestingly, several species of Leishmania have been shown to bear an endogenous cytoplasmic dsRNA virus (LRV) of the Totiviridae family, and recently we correlated the presence of LRV1 within Leishmania parasites to an exacerbation murine leishmaniasis and with an elevated frequency of drug treatment failures in humans. This raises the possibility of further exacerbation of leishmaniasis in the presence of both viruses, and here we report a case of cutaneous leishmaniasis caused by Leishmania braziliensis bearing LRV1 with aggressive pathogenesis in an HIV patient. LRV1 was isolated and partially sequenced from skin and nasal lesions. Genetic identity of both sequences reinforced the assumption that nasal parasites originate from primary skin lesions. Surprisingly, combined antiretroviral therapy did not impact the devolution of Leishmania infection. The Leishmania infection was successfully treated through administration of liposomal amphotericin B. PMID- 26834199 TI - Performance of Interferon-Gamma and IP-10 Release Assays for Diagnosing Latent Tuberculosis Infections in Patients with Concurrent Malaria in Tanzania. AB - Interferon-gamma (IFN-gamma) release assays (IGRAs) are used to detect cellular immune recognition of Mycobacterium tuberculosis The chemokine IFN-gamma inducible protein 10 (IP-10) is an alternative diagnostic biomarker to IFN-gamma. Several conditions interfere with IGRA test performance. We aimed to assess the possible influence of Plasmodium falciparum infection on the IGRA test QuantiFERON-TB GOLD(r) In-Tube (QFT) test and an in-house IP-10 release assay. In total, 241 Tanzanian adults were included; 184 patients with uncomplicated malaria (88 human immunodeficiency virus [HIV] coinfected) and 57 HIV-infected patients without malaria infection. Malaria was treated with artemether lumefantrine (Coartem(r)). QFT testing was performed before initiation of malaria treatment and at days 7 and 42. In total, 172 patients completed follow-up. IFN gamma and IP-10 was measured in QFT supernatants. We found that during malaria infection IFN-gamma and IP-10 levels in the unstimulated samples were elevated, mitogen responsiveness was impaired, and CD4 cell counts were decreased. These alterations reverted after malaria treatment. Concurrent malaria infection did not affect QFT test results, whereas there were more indeterminate IP-10 results during acute malaria infection. We suggest that IGRA and IP-10 release assay results of malaria patients should be interpreted with caution and that testing preferably should be postponed until after malaria treatment. PMID- 26834202 TI - Peptide Transport and Metabolism by the Lactating Mammary Gland. PMID- 26834200 TI - Enzootic Arbovirus Surveillance in Forest Habitat and Phylogenetic Characterization of Novel Isolates of Gamboa Virus in Panama. AB - Landscape changes occurring in Panama, a country whose geographic location and climate have historically supported arbovirus transmission, prompted the hypothesis that arbovirus prevalence increases with degradation of tropical forest habitats. Investigations at four variably degraded sites revealed a diverse array of potential mosquito vectors, several of which are known vectors of arbovirus pathogens. Overall, 675 pools consisting of 25,787 mosquitoes and representing 29 species from nine genera (collected at ground and canopy height across all habitats) were screened for cytopathic viruses on Vero cells. We detected four isolates of Gamboa virus (family:Bunyaviridae; genus:Orthobunyavirus) from pools of Aedeomyia squamipennis captured at canopy level in November 2012. Phylogenetic characterization of complete genome sequences shows the new isolates to be closely related to each other with strong evidence of reassortment among the M segment of Panamanian Gamboa isolates and several other viruses of this group. At the site yielding viruses, Soberania National Park in central Panama, 18 mosquito species were identified, and the predominant taxa included A. squamipennis,Coquillettidia nigricans, and Mansonia titillans. PMID- 26834205 TI - Acute respiratory distress syndrome after accidental inhalation of fluorocarbon monomers and pyrolysis products. PMID- 26834206 TI - Heart failure and left ventricular remodelling in HFrEF and HFpEF. PMID- 26834201 TI - A Systematic Review of Toxocariasis: A Neglected But High-Prevalence Disease in Brazil. AB - Toxocariasis is an anthropozoonosis that occurs in all parts of the world. In particular, this disease can often be found in developing countries and in regions, where basic sanitation conditions are poor. However, industrialized countries have reported seroprevalence rates as high as 14.2% in humans. The definitive hosts of the disease are dogs and cats, whereas humans are a paratenic host. To determine the burden of toxocariasis in Brazil, we followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to conduct a systematic review of the literature. Using keywords and applying the established criteria, we identified 160 publications and selected 22 articles for further analysis. The seroprevalence of toxocariasis in various regions of the country ranged from 4.2% to 65.4%. The highest prevalence was found in the northeast region, although the majority of the studies identified were from the southeast region. The findings suggest the importance of raising awareness among health professionals and public authorities about the fact that toxocariasis is a health problem. PMID- 26834207 TI - CardioPulse: The Postgraduate Course in Heart Failure. PMID- 26834209 TI - Patellofemoral pain. AB - Patellofemoral pain refers to pain behind or around the patella (also known as patellofemoral pain syndrome, anterior knee pain, runner's knee, and, formerly, chondromalacia patellae). Patellofemoral pain is common, accounting for 11-17% of all knee pain presentations to general practice.(1 2) While it typically occurs in physically active people aged <40 years, it also affects people of all activity levels and ages.(1 2) Patellofemoral pain can be diagnosed in the clinic, and evidence based treatments can reduce pain and improve function, allowing patients to maintain a physically active lifestyle. PMID- 26834210 TI - GREM1 Is a Key Regulator of Synoviocyte Hyperplasia and Invasiveness. AB - OBJECTIVE: To investigate the expression of Gremlin 1 (GREM1), an antagonist of bone morphogenetic protein, in rheumatoid arthritis (RA) synovia and its involvement in the hyperplasia and invasiveness of fibroblast-like synoviocytes of RA (RA-FLS). METHODS: Computational analysis was introduced to identify FLS predominant regulators. GREM1 expression was examined by immunohistochemistry, real-time PCR, and ELISA. FLS proliferation and apoptosis were determined using tetrazolium-based colorimetric assay and APOPercentage assay, respectively. FLS migration and invasion were evaluated by wound migration and Matrigel invasion assay, respectively. Expressions of Bax, Bcl2, pErk1/2, and pAkt were detected by Western blot analysis. RESULTS: Through global transcriptome profiling, we identified a GREM1 gene predominantly expressed in RA-FLS. Indeed, the GREM1 expression was higher in synovia, synovial fluids, and FLS of patients with RA than in those of patients with osteoarthritis, and its levels correlated well with proinflammatory cytokine concentrations. Knockdown of GREM1 transcripts using short interfering RNA (siRNA) reduced the proliferation and survival of RA FLS along with downregulation of pErk1/2, pAkt, and Bcl2 expressions, whereas it induced Bax expression. Conversely, the addition of recombinant GREM1 to RA-FLS showed the opposite results. Moreover, GREM1 siRNA decreased the migratory and invasive capacity of RA-FLS, whereas exogenous GREM1 increased it. The GREM1 induced FLS survival, migration, and invasion were completely blocked by neutralizing antibodies to alphanubeta3 integrin on RA-FLS, suggesting that alphanubeta3 integrin mediates the antiapoptotic and promigratory effects of GREM1. CONCLUSION: GREM1 is highly expressed in RA joints, and functions as a regulator of survival, proliferation, migration, and invasion of RA-FLS. PMID- 26834211 TI - Efficacy and Safety of Subcutaneous and Intravenous Loading Dose Regimens of Secukinumab in Patients with Active Rheumatoid Arthritis: Results from a Randomized Phase II Study. AB - OBJECTIVE: To evaluate the efficacy and safety of secukinumab, a fully human antiinterleukin-17A monoclonal antibody, administered with an intravenous (IV) or subcutaneous (SC) loading regimen versus placebo, in patients with active rheumatoid arthritis (RA). METHODS: In this phase II, double-blind, double-dummy, 52-week study (ClinicalTrials.gov NCT01359943), 221 patients with inadequate response to methotrexate were randomized (2:2:1) to secukinumab, IV loading 10 mg/kg at baseline, Weeks 2 and 4, then SC 150 mg every 4 weeks (n = 88); secukinumab SC loading 150 mg once weekly for 5 weeks, then every 4 weeks (n = 89); or a matching placebo (followed by secukinumab 150 mg every 4 weeks starting Week 16; n = 44). The primary endpoint was superior efficacy of pooled secukinumab versus placebo using American College of Rheumatology 20% response (ACR20) at Week 12. RESULTS: The primary efficacy endpoint was not met: ACR20 response at Week 12 was 49.2% for pooled secukinumab versus 40.9% for placebo (p = 0.3559). These variables improved significantly with pooled secukinumab versus placebo at Week 12 (all p < 0.05): the 28-joint Disease Activity Score (DAS28), patient's and physician's global assessment of disease activity, patient's assessment of RA pain, and high-sensitivity C-reactive protein levels. Results of continuous efficacy outcomes were similar between the IV and SC loading regimens. The most frequent adverse events were infections, with similar rates across secukinumab and placebo. CONCLUSION: Although the primary endpoint (ACR20) was not met, secukinumab demonstrated improved efficacy in reducing disease activity over placebo as measured by DAS28 and other secondary endpoints. PMID- 26834212 TI - Clinical Characteristics and Cytokine Profiles of Organizing Pneumonia in Patients with Rheumatoid Arthritis Treated with or without Biologics. AB - OBJECTIVE: It has been reported that organizing pneumonia (OP) develops when patients with rheumatoid arthritis (RA) are treated with biologic disease modifying antirheumatic drugs (bDMARD). However, the clinical characteristics and pathophysiology of OP in RA remain unknown in patients treated with bDMARD. We investigated the clinical characteristics and cytokine profiles of patients with RA-OP treated with bDMARD or conventional synthetic DMARD (csDMARD). METHODS: Twenty-four patients with RA who had developed OP were enrolled. These patients included 12 treated with bDMARD (bDMARD-OP subset) and 12 treated with csDMARD (csDMARD-OP subset). We compared the clinical characteristics and cytokine profiles between the patients with OP (OP subset, n = 24) and non-OP patients (non-OP subset, n = 29). RESULTS: There was no significant difference in clinical characteristics between the OP subset and the non-OP subset. Four patients developed OP within 2 months of bDMARD administration. In the other 8 patients, OP developed more than 1 year after the initiation of bDMARD. OP improved with corticosteroid treatment in all bDMARD-OP patients. After OP improved, bDMARD were readministered in 6 patients, and no OP recurrence was observed in any of these patients. Our multivariate analysis revealed that serum levels of interferon-alpha (IFN-alpha), interleukin (IL)-1beta, IL-6, IL-8, and interferon gamma-inducible protein 10 were significantly associated with the development of OP, although these cytokines tended to be lower in the bDMARD-OP subset than in the csDMARD-OP subset. CONCLUSION: OP is unlikely to be fatal in patients treated with bDMARD or csDMARD. IFN-alpha and proinflammatory cytokines are associated with the pathophysiology of OP in RA. PMID- 26834213 TI - Efficacy and Safety of Baricitinib in Japanese Patients with Active Rheumatoid Arthritis Receiving Background Methotrexate Therapy: A 12-week, Double-blind, Randomized Placebo-controlled Study. AB - OBJECTIVE: To evaluate efficacy and safety, baricitinib [Janus kinase (JAK) 1/JAK2 inhibitor] was compared with placebo in Japanese patients with active rheumatoid arthritis (RA) despite background treatment with methotrexate (MTX). METHODS: This was a phase IIB, double-blind, randomized, placebo-controlled study (clinicaltrials.gov: NCT01469013). Patients had moderate to severe active adult onset RA despite stable treatment with MTX. Patients (n = 145) were randomized in a 2:1:1:1:1 ratio to placebo or 1 mg, 2 mg, 4 mg, or 8 mg oral baricitinib daily for 12 weeks. The primary analysis compared the combined 4/8-mg dose groups with placebo for the American College of Rheumatology (ACR) 20 response rate at 12 weeks. Other outcomes included additional measures of disease activity, physical function, laboratory abnormalities, and adverse events. RESULTS: A significantly higher proportion of patients in the combined 4/8-mg baricitinib group (37/48, 77%) compared with the placebo group (15/49, 31%) had at least an ACR20 response after 12 weeks of treatment (p < 0.001). Significant improvements in disease activity, remission, and physical function were observed as early as Week 2 of treatment with baricitinib, particularly with daily doses of >= 4 mg. Only 1 patient receiving baricitinib discontinued because of an adverse event. Adverse event rates with baricitinib doses <= 4 mg daily were similar to placebo, but there was a higher incidence of adverse events and laboratory abnormalities in the 8-mg group. CONCLUSION: In this phase II study, baricitinib was well tolerated and rapidly improved the signs, symptoms, and physical function of Japanese patients with active RA, supporting continued development of baricitinib (clinicaltrials.gov NCT01469013). PMID- 26834214 TI - Longitudinal Evaluation of Lipoprotein Variables in Systemic Lupus Erythematosus Reveals Adverse Changes with Disease Activity and Prednisone and More Favorable Profiles with Hydroxychloroquine Therapy. AB - OBJECTIVE: Systemic lupus erythematosus (SLE) is associated with accelerated atherosclerotic cardiovascular disease. Patients with SLE have adverse lipoprotein variables, but little is known about how these change with treatment and disease activity. The nuclear magnetic resonance LipoProfile test contains a glycoprotein signal-termed GlycA, an inflammatory marker, which has not been evaluated in SLE. We assessed patients longitudinally to determine how lipoproteins and GlycA change with active SLE. METHODS: Sera from selected clinical visits of patients in the Hopkins Lupus Cohort were analyzed for lipoprotein and GlycA levels. Univariate and multivariate analyses were performed to evaluate lipoprotein variables and their relationship to ethnicity, disease activity, prednisone use, and hydroxychloroquine (HCQ) therapy. RESULTS: Fifty two patients were included over 229 visits. Adverse changes in lipoprotein variables with disease activity were demonstrated. For each point increase in the Systemic Lupus Erythematosus Disease Activity Index, there was a decrease in high density lipoprotein (HDL) even after adjusting for corticosteroid use. Prednisone was associated with higher very low-density lipoprotein, low-density lipoprotein, HDL, and triglycerides. HCQ was associated with more favorable variables. GlycA levels were higher than in normal populations and increased with disease activity. CONCLUSION: Adverse changes in lipoprotein profiles were associated with SLE activity and prednisone therapy. This gives insight into mechanisms of atherosclerosis in SLE. Favorable lipoprotein variables occurred in those taking HCQ. GlycA increased with disease activity and was higher than in healthy populations. PMID- 26834215 TI - Birth Outcomes in Women with a History of Juvenile Idiopathic Arthritis. AB - OBJECTIVE: To determine whether children born to women who had juvenile idiopathic arthritis (JIA) had more adverse birth outcomes than children born to mothers who never had JIA. METHODS: Our cohort study used data from physician billing and hospitalizations covering the province of Quebec, Canada. We identified all women with JIA with a first-time birth between January 1, 1983, and December 31, 2010, and assembled a control cohort of first-time mothers without JIA from the same administrative data, matching 4:1 for date of first birth, maternal age, and area of residence. We compared outcomes (stillbirth, prematurity, small for gestational age, and major congenital anomalies) in the JIA versus non-JIA groups using logistic regression. RESULTS: Mean age at delivery was 24.7 years in the JIA group (n = 1681) and 25.0 years for the non JIA group (n = 6724). Women who had JIA were at higher risk for a premature baby [adjusted relative risk (RR) 1.20, 95% CI 1.01-1.42], a baby small for gestational age (adjusted RR 1.19, 95% CI 1.04-1.37), and a child with a congenital malformation (adjusted RR 6.51, 95% CI 5.05-8.39). Neural tube defects were higher in the JIA offspring: 1.61% (95% CI 1.11-2.33) versus 0.03% (95% CI 0.01-0.11) in the non-JIA group, as were congenital heart defects: 1.07% (95% CI 0.68-1.69) versus 0.58% (95% CI 0.42-0.79). CONCLUSION: Most women with JIA will deliver a normal baby, even though they are at higher risk for having a child with adverse birth outcomes. Research is needed to understand pathophysiologic mechanisms and to investigate the effects of medications during childhood and youth on future birth outcomes. PMID- 26834216 TI - Nonsteroidal Antiinflammatory Drugs for Axial Spondyloarthritis: A Cochrane Review. AB - OBJECTIVE: To determine the benefits and harms of nonsteroidal antiinflammatory drugs (NSAID) in axial spondyloarthritis (axSpA). METHODS: Systematic review using Cochrane Collaboration methodology. INCLUSION CRITERIA: randomized controlled trials (RCT) and quasi-RCT (to June 2014), investigating NSAID versus any control for axSpA, and observational studies of longterm effects (>= 6 mos) of NSAID on radiographic progression or adverse events. Main outcomes were pain, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, radiographic progression, number of withdrawals because of adverse events, and number of serious adverse events. Risk of bias was assessed. RESULTS: Thirty-five RCT, 2 quasi-RCT, and 2 cohort studies were included. Twenty-nine RCT and 2 quasi-RCT (n = 4356) were included in pooled analyses [traditional NSAID vs placebo (n = 5), cyclooxygenase-2 (COX-2) vs placebo (n = 3), COX-2 vs traditional NSAID (n = 4), NSAID vs NSAID (n = 24), naproxen vs other NSAID (n = 3), and low- vs high-dose NSAID (n = 5)]. Compared with placebo, both traditional and COX-2 NSAID were consistently more efficacious at 6 weeks and equally safe after 12 weeks. No significant differences in benefits or harms between the 2 NSAID classes and no important differences in benefits or withdrawals because of adverse events between different NSAID were found, especially if studies with high risk of bias were excluded. Single studies suggest NSAID may retard radiographic progression, especially by continuous rather than on-demand NSAID use. CONCLUSION: High quality evidence indicates that both traditional and COX-2 NSAID are efficacious for treating axSpA, and harms are not different from placebo in the short term. Various NSAID are equally effective. PMID- 26834217 TI - Disparities in Outcomes for African Americans and Whites Undergoing Total Knee Arthroplasty: A Systematic Literature Review. AB - OBJECTIVE: African Americans in the United States undergo total knee arthroplasty (TKA) less often than whites, in part because of lower expectations among African Americans for successful surgery. Whether this lower expectation is justified is unknown. Our objective is to compare health-related quality of life (HRQOL) and satisfaction after TKA between African Americans and whites. METHODS: A systematic review of English language articles using Medline, the Cochrane register, Embase (April 21, 2015), and a hand search of unlisted disparities journals was performed. Search terms included total knee replacement, quality of life, outcomes, and satisfaction. High-quality cohort studies that examined HRQOL in African Americans and white adults 6 months or more after TKA were included. RESULTS: Of the 4781 studies screened by title, and 346 by abstract, 7 studies included race in their analysis. Results included 5570 TKA patients, 4077 whites (89%), and 482 (11%) blacks. Because studies used different outcome measures and were inconsistent in their adjustment for confounders, we could not perform a quantitative synthesis of results. In 5 studies, US blacks had worse pain, in 5 worse function, and in 1 less satisfaction 6 months to 2 years after TKA. CONCLUSION: US blacks may derive less benefit from TKA than whites as measured by HRQOL, pain, function, and satisfaction. Many studies assessing predictors of patient-related TKA outcomes fail to analyze race as a variable, which limited our study. More studies assessing the effect of race and socioeconomic factors on TKA outcome are needed. PMID- 26834218 TI - Comparison of Clinical Examination versus Whole-body Magnetic Resonance Imaging of Enthesitis in Patients with Early Axial Spondyloarthritis during 3 Years of Continuous Etanercept Treatment. AB - OBJECTIVE: To compare clinical examination versus whole-body magnetic resonance imaging (WB-MRI) of enthesitis in patients with early axial spondyloarthritis during 3 years of continuous etanercept (ETN) treatment. METHODS: Forty-one patients underwent clinical and WB-MRI examinations for enthesitis at baseline and after 2 and 3 years of treatment. Twenty-one sites were assessed in 4 anatomic regions - anterior chest wall, pelvis, knee, and foot. RESULTS: Clinical examination at baseline detected enthesitis in 57% of the patients (85 lesions, mean 2.1 lesions, SD 2.9), most of them in the pelvis (42 lesions in 17 patients) and anterior chest wall (19 lesions in 10 patients). The proportion of patients with clinically detected enthesitis decreased to 19% at Year 2 (mean 0.5, SD 1.5) and 14% at Year 3 (mean 0.7, SD 1.8). WB-MRI detected enthesitis at baseline in 21% of patients (22 lesions, mean 0.5 lesions, SD 1.1), also most frequently in the pelvis (12 lesions) and anterior chest wall (7 lesions). MRI-positive enthesitis decreased to 13% at Year 2 (mean 0.2 lesions, SD 0.5) and 14% at Year 3 (mean 0.2 lesions, SD 0.5). There was positive correlation of clinical and MRI findings at baseline at the anterior chest wall (p = 0.001) and the pelvis (p = 0.0001). No correlation was found at the knee and foot at baseline and for all regions at followup. CONCLUSION: Both clinical examination and WB-MRI show a decrease in enthesitis after 2 and 3 years of ETN treatment, but correlation was limited to the pelvis and anterior chest wall at baseline. PMID- 26834219 TI - Risk of Psychiatric Disorders following Ankylosing Spondylitis: A Nationwide Population-based Retrospective Cohort Study. AB - OBJECTIVE: Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease. A higher prevalence of psychiatric comorbidities, including depressive disorder, has been proven in patients with AS. However, a clear temporal causal relationship between AS and psychiatric disorders has not been well established. We performed a nationwide population-based retrospective cohort study to analyze the relationship between AS and the subsequent development of psychiatric disorders, including schizophrenia, bipolar disorder, depressive disorders, anxiety disorders, and sleep disorders. METHODS: We identified subjects who were newly diagnosed with AS between January 1, 2000, and December 31, 2008, in the Taiwan National Health Insurance (NHI) Research Database. A comparison cohort was constructed of patients without AS who were matched according to age and sex. All patients with AS and control patients were observed until diagnosed with psychiatric disorders, or until death or withdrawal from the NHI system, or until December 31, 2009. RESULTS: The AS cohort consisted of 2331 patients and the comparison cohort consisted of 9324 matched control patients without AS. The adjusted HR for depressive disorders, anxiety disorders, and sleep disorders in subjects with AS were higher than those of the controls during followup (HR 1.718, 95% CI 1.303-2.265; HR 1.848, 95% CI 1.369-2.494; and HR 1.494, 95% CI 1.031-2.162, respectively). CONCLUSION: AS might increase the risk of a subsequent newly diagnosed depressive disorder, anxiety disorder, or sleep disorder, but not schizophrenia or bipolar disorder. These observations highlight the need for psychiatric evaluation and intervention for patients with AS. PMID- 26834220 TI - Myeloid-related Protein 8/14 Levels in Rheumatoid Arthritis: Marker of Disease Activity and Response to Methotrexate. AB - OBJECTIVE: Myeloid-related proteins (MRP) 8/14 belong to a family of calcium binding proteins produced by myeloid cells. Baseline serum levels of MRP8/14 have been shown to predict response to biologicals in rheumatoid arthritis (RA). Because methotrexate (MTX) is the first-line therapy in RA, we studied whether MRP8/14 levels can predict response to MTX. METHODS: Patients with active RA disease who were naive to disease-modifying antirheumatic drugs were enrolled. All patients were treated with MTX only, to a maximum of 25 mg/week or the maximal tolerated dose. At 4 months, the European League Against Rheumatism response was assessed. All patients who needed rescue therapy after 2 months or who did not respond at 4 months were classified as nonresponders. RESULTS: Ninety patients were enrolled, of whom 3 discontinued MTX within 4-6 weeks, so 87 patients were analyzed [74 women, median (interquartile range; IQR) for the Disease Activity Score at 28 joints (DAS28) was 4.43 (4.1-5.1)]. The median (IQR) serum MRP8/14 level at baseline was 19.95 ug/ml (11.49-39.06). The serum MRP8/14 had good correlation with DAS28-C-reactive protein (CRP; r = 0.35, p = 0.001). The MRP8/14 levels fell significantly after 4 months of treatment (10.28 ug/ml, 5.95-16.05, p < 0.001). Among 87 patients, 69 were responders. The median (IQR) baseline level of MRP8/14 was higher among responders compared with nonresponders: 23.99 ug/ml (15.39-42.75) versus 9.58 ug/ml (6.11-24.93, p = 0.00250). The levels declined in the responders, from 23.99 ug/ml (15.39-42.75) to 10.41 ug/ml (5.83-15.61, p < 0.001), but not in the nonresponders, from 9.58 ug/ml (6.11-24.93) to 9.19 ug/ml (7.74-21.96, p = 0.687). Receiver-operation characteristic analysis showed that MRP8/14 was a better predictor of response than CRP and erythrocyte sedimentation rate, especially with early disease onset (< 1-yr duration). CONCLUSION: MRP8/14 is a good marker of disease activity in RA, and higher levels predict response to MTX. PMID- 26834221 TI - Quantitative Alterations of Capillary Diameter Have a Predictive Value for Development of the Capillaroscopic Systemic Sclerosis Pattern. AB - OBJECTIVE: To quantify earlier capillary diameter abnormalities, observed by nailfold videocapillaroscopy (NVC), in primary Raynaud phenomenon (PRP) subjects compared with RP subjects later evolved to systemic sclerosis (SSc)-associated secondary Raynaud phenomenon (SRP). METHODS: There were 6112 NVC images of 191 subjects analyzed at baseline and after a mean followup of 42.77 +/- 35.80 months. We selected 48 patients affected by SRP and 143 matched controls confirmed with PRP. The diameter of the most dilated limbs (arterial, venous, and apical) was measured in 16 images per subject. Statistical analysis was performed using nonparametric tests. The threshold values for capillary diameters associated with the development of SSc-associated SRP were determined through receiver-operating characteristic curves. RESULTS: Mean capillary diameter values were significantly different for arterial, venous, and average diameters (mean value of arterial, venous, and apical) between patients with PRP and SRP (p < 0.0001). These alterations were found to be independent predictors for disease development (p = 0.015). Threshold values of 30 um (area under the curve = 0.802, sensitivity/specificity = 0.85/0.63) to 31 um were identified for average, arterial, and venous diameters, with a shortening effect on time to disease development. CONCLUSION: The study showed that capillary diameter is an independent predictor for development of SSc-associated SRP. Progression to SRP is unlikely for subjects affected by RP when average capillary diameter is under 30 MUm. Subsequently, the execution of the qualitative/quantitative integrated analysis should be part of the NVC followup of RP subjects. PMID- 26834223 TI - Assessment, Definition, and Classification of Lower Limb Ulcers in Systemic Sclerosis: A Challenge for the Rheumatologist. AB - OBJECTIVE: To evaluate pathogenesis and clinical features of lower limb ulcers in systemic sclerosis (SSc) and to propose a classification that could be used in clinical practice. METHODS: Charts of 60 patients with SSc who had lower limb cutaneous lesions were reviewed. All patients had videocapillaroscopy and arterial and venous lower limb color Doppler ultrasonography (US). Arteriography was performed if occlusive peripheral arterial disease was suspected. RESULTS: The 554 lesions were classified as hyperkeratosis, ulcers, and gangrenes. There were 341 (61.6%) hyperkeratoses, 208 (37.5%) ulcers, and 5 (0.9%) gangrenes. Ulcers were divided into pure ulcers, ulcers associated with hyperkeratosis, and ulcers secondary to calcinosis. Involvement of arterial and venous macrocirculation as determined by color Doppler US was observed in 17 (18.3%) and 18 (30%) patients, respectively. Seventeen out of 37 patients with pure ulcers (45.9%) presented neither venous insufficiency nor hemodynamically significant macrovascular arterial disease. In these patients, pure ulcers were most likely caused by isolated SSc-related microvascular involvement (pure microvascular ulcers). The only significant risk factor for development of pure microvascular ulcers in the multivariate analysis was the history of lower limb ulcers (OR 26.67, 95% CI 2.75-259.28; p < 0.001). CONCLUSION: Results of our study indicate that lower limb ulcers in SSc often have a multifactorial pathogenesis that may be difficult to manage. Further studies are needed to validate the proposed classification and to assess the most appropriate management of lower limb ulcers in SSc. PMID- 26834224 TI - Trends in the Diagnosis and Management of Pediatric Appendicitis. AB - * On the basis of class B evidence and consensus, acute appendicitis in children can often be diagnosed clinically with only selective use of imaging. (13)(14)(15)(16) * On the basis of class B evidence and consensus, ultrasonography is the test of choice when acute appendicitis is suspected but is unclear based on history, physical examination, and laboratory results. (17)(18)(19) * On the basis of class B evidence and consensus, the use of computed tomography scan should be limited to cases of suspected complex appendicitis with abscess or when there is clinical suspicion for acute appendicitis but ultrasonography results are not helpful. (16) * On the basis of class C evidence and consensus, children with possible appendicitis ideally should be treated in medical centers that have skilled sonographic personnel. (21) * On the basis of class B evidence and consensus, simple appendicitis should be treated by appendectomy during normal operating hours. Preoperative treatment with intravenous antibiotics and fluids during the overnight hours halts disease progression and allows for the safest surgery with the benefit of a full and rested staff. (24)(25)(26) * On the basis of class B evidence and consensus, complex appendicitis with a well-defined abscess can be treated nonoperatively initially, with the option of an interval appendectomy after recovery from the acute infection. (29)(30) (31)(32)(33) PMID- 26834222 TI - Assessment of the New 2012 EULAR/ACR Clinical Classification Criteria for Polymyalgia Rheumatica: A Prospective Multicenter Study. AB - OBJECTIVE: To assess the performance of the new 2012 provisional European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) polymyalgia rheumatica (PMR) clinical classification criteria in discriminating PMR from other mimicking conditions compared with the previous 5 diagnostic criteria in a multicenter prospective study. METHODS: Patients older than 50 years, presenting with new-onset bilateral shoulder pain with elevated acute-phase reactants (APR), were assessed for the fulfillment of the new and old classification/diagnostic criteria sets for PMR. At the end of the 1-year followup, 133 patients were diagnosed with PMR (expert opinion) and 142 with non-PMR conditions [69 rheumatoid arthritis (RA)]. Discriminating capacity, sensitivity, and specificity of the criteria sets were estimated. RESULTS: Discriminating capacity of the new clinical criteria for PMR from non-PMR conditions and RA as estimated by area under the curve (AUC) were good with AUC of 0.736 and 0.781, respectively. The new criteria had a sensitivity of 89.5% and a specificity of 57.7% when tested against all non-PMR cases. When tested against all RA, seropositive RA, seronegative RA, and non-RA control patients, specificity changed to 66.7%, 100%, 20.7%, and 49.3%, respectively. Except for the Bird criteria, the 4 previous criteria had lower sensitivity and higher specificity (ranging from 83%-93%) compared with the new clinical criteria in discriminating PMR from all other controls. CONCLUSION: The new 2012 EULAR/ACR clinical classification criteria for PMR is highly sensitive; however, its ability to discriminate PMR from other inflammatory/noninflammatory shoulder conditions, especially from seronegative RA, is not adequate. Imaging and other modifications such as cutoff values for APR might increase the specificity of the criteria. PMID- 26834225 TI - Protozoan Parasites. AB - * Stool antigen detection for Cryptosporidium sp, Giardia lamblia and Entamoeba histolytica are now commercially available, have better sensitivity and specificity than the traditional stool microscopy, and are less dependent on personnel skill. Tests employing newer techniques with faster turnaround time are also available for diagnosing trichomoniasis.* Nitazoxanide, the only U.S. Food and Drug Administration-approved medication for therapy of cryptosporidiosis, is effective among immunocompetent patients. However, on the basis of strong evidence from multiple clinical trials, nitazoxanide is considered ineffective among immunocompromised patients. (14) * Giardiasis can be asymptomatic or have a chronic course leading to malabsorption and failure to thrive. It can be treated with metronidazole, tinidazole, or nitazoxanide. On the basis of growing observational studies, postinfectious and extraintestinal manifestations of giardiasis occur, but the mechanisms are unclear. Given the high prevalence of giardiasis, public health implications need to be defined. (16) * Eradicating E histolytica from the gastrointestinal tract requires only intraluminal agent therapy. Therapy for invasive illnesses requires use of imidazole followed by intraluminal agents to eliminate persistent intraluminal parasites. * Malaria is considered the most lethal parasitic infection, with Plasmodium falciparum as the predominant cause of mortality. P vivax and P ovale can be dormant in the liver, and primaquine is necessary to resolve infection by P vivax and P ovale. * Among immunocompetent patients, infection with Toxoplasma gondii may be asymptomatic, involve localized lymphadenopathy, or cause ocular infection. In immunocompromised patients, reactivation or severe infection is not uncommon. On the basis of limited observational studies (there are no well-controlled randomized trials), therapy is recommended for acute infection during pregnancy to prevent transmission to the fetus/infant or decrease infectious sequelae to the fetus. (2) * On the basis of growing research evidence as well as consensus, trichomoniasis is associated with many health-related concerns, including adverse pregnancy outcomes and increased risk of acquisition and transmission of human immunodeficiency virus. (3)(25) Similar to toxoplasmosis,many infections are asymptomatic, and the true public health impact of trichomoniasis is difficult to define. Further research is warranted. PMID- 26834226 TI - Knee Pain in Children, Part II: Limb- and Life-threatening Conditions, Hip Pathology, and Effusion. AB - On the basis of primarily consensus due to lack of relevant clinical studies, the most important evaluative step for knee pain is to identify any emergent conditions, including limb- and life-threatening disorders (septic arthritis, osteomyelitis, and malignancy), hip pathology, or conditions associated with effusions. (2)(3)(6)(8)(11)(13)(14) PMID- 26834227 TI - Case 1: Abdominal Pain and Seizure in a 4-year-old Boy. PMID- 26834228 TI - Case 2: Generalized Anasarca in 15-year-old Girl With Type 1 Diabetes Mellitus. PMID- 26834230 TI - Exocrine Pancreatic Insufficiency. PMID- 26834229 TI - Case 3: Abdominal Pain, Nausea, and Vomiting in a 12-year-old Girl. PMID- 26834231 TI - Visual Diagnosis: New Lung Nodules in a 3-year-old Girl with Wilms Tumor. AB - The most significant oncologic concern with finding new pulmonary nodules on imaging in a pediatric patient who has anaplastic Wilms tumor is progressive disease with new pulmonary metastases. This case emphasizes the importance of employing a creative clinical differential diagnosis, even for patients with known underlying oncologic disease. PMID- 26834232 TI - Re: Late diagnosis of isolated congenitally corrected transposition of the great arteries in a 92-year old woman. PMID- 26834233 TI - Low-flow low-gradient aortic stenosis: surgical outcomes and mid-term results after isolated aortic valve replacement. AB - OBJECTIVES: To analyse operative outcomes and mid-term results following isolated aortic valve replacement (AVR) in patients with low-flow low-gradient severe aortic stenosis (LFLG AS) compared with normal flow high-gradient aortic stenosis (NFHG AS). METHODS: A retrospective analysis of data for all isolated AVRs performed for AS at our centre in the last 17 years (n = 846). Two groups were identified: LFLG AS (n = 198, 23%) [subdivided into: True LFLG AS (n = 66, 33%) and paradoxical LFLG AS (n = 132, 67%)] and NFHG AS (n = 648, 77%). Follow-up was done by clinical visits and telephone interviews. The mean follow-up was 5.8 +/- 4.2 years. RESULTS: The mean age was 71.5 +/- 9.7 years in the LFLG AS group and 68.7 +/- 10.8 years in the NFHG group (P = 0.01). The LFLG AS group had a mean gradient 31.2 +/- 7.4 mmHg compared with 59.1 +/- 16.6 mmHg in the NFHG group (P = 0.001). Diabetes, chronic obstructive pulmonary disease, previous coronary disease, peripheral vascular disease, atrial fibrillation and pulmonary hypertension were significantly more frequent in the LFLG AS patients (P < 0.01). The in-hospital mortality rate was 2% in the LFLG and 1% in the NFHG group, P = 0.13. One- and 5-year mortality rates were significantly higher in the LFLG group (13 and 28 vs 4 and 16% in the NFHG, respectively, P = 0.001). Patients with true LFLG AS also had a significantly higher long-term mortality than those with paradoxical LFLG AS (27 vs 6% at 1 year and 42 vs 20% at 5 years, P < 0.05). CONCLUSIONS: AVR in patients with LFLG AS is associated with similar surgical mortality but increased mid-term mortality compared with NFHG AS. Patients with true LFLG AS have the worst outcomes. Surgery should still be offered for LFLG AS on prognostic grounds and for symptomatic benefit among survivors. PMID- 26834234 TI - Minimal invasive extracorporeal circulation should become the standard practice in coronary revascularization surgery. PMID- 26834235 TI - Two lives. PMID- 26834236 TI - The impact of certification of general thoracic surgeons on lung cancer mortality: a survey by The Japanese Association for Thoracic Surgery. AB - OBJECTIVES: The Japanese Board of General Thoracic Surgery and the annual survey by the Japanese Association for Thoracic Surgery (JATS) of certified hospitals began in 2005; since then, over 1300 specialists and 650 hospitals have been certified by this system. To evaluate how this system contributes to improving the outcomes of general thoracic surgery, the effects of the number of certified general thoracic surgeons (GTSs) and hospital volume on 30-day mortality or hospital mortality were evaluated. METHODS: Using data from the annual survey of JATS from 2005 to 2012, the outcomes of 211 619 patients who underwent lung resection for lung cancer were evaluated. The patients were divided into four groups by the level of surgery: first level, partial resection; second level, segmentectomy and lobectomy; third level, sleeve segmentectomy and lobectomy; and fourth level, pneumonectomy, sleeve pneumonectomy and pleuro-pneumonectomy. Multiple logistic regression analysis was used to examine the associations between operative mortality and the number of GTSs, hospital volume and level of surgical procedure. RESULTS: Overall 30-day and hospital mortality rates were 0.40 and 0.77%, respectively. The 30-day and hospital mortality rates for each surgical level were 0.20 and 0.35% for the first level, 0.36 and 0.73% for the second level, 1.02 and 1.81% for the third level and 2.42 and 4.26% for the fourth level, respectively. The number of GTSs was associated with lower 30-day and hospital mortality rates (P < 0.0001). On logistic analysis, number of GTSs (<3 vs >=3), hospital volume (<50 vs >=50) and level of procedure (1 vs 2, 3 vs 2, 4 vs 2) were significantly associated with 30-day and hospital mortality rates. For 30-day mortality, the odds ratios were 0.688 (P < 0.0001) for higher number of GTSs and 0.856 (P = 0.0510) for higher volume hospitals. In the subgroup analysis by surgical level, low 30-day and hospital mortality rates in the second and fourth surgical levels were correlated with a higher number of GTSs. CONCLUSIONS: The current decrease in overall 30-day mortality rates from the JATS data showed greater dependence on the number of GTSs than on the hospital volume. We believe that the certification system in Japan is useful for the establishment of GTS status. PMID- 26834237 TI - Optogenetic stimulation of Drosophila heart rate at different temperatures and Ca2+ concentrations. AB - Optogenetics is a revolutionary technique that enables noninvasive activation of electrically excitable cells. In mammals, heart rate has traditionally been modulated with pharmacological agents or direct stimulation of cardiac tissue with electrodes. However, implanted wires have been known to cause physical damage and damage from electrical currents. Here, we describe a proof of concept to optically drive cardiac function in a model organism, Drosophila melanogaster. We expressed the light sensitive channelrhodopsin protein ChR2.XXL in larval Drosophila hearts and examined light-induced activation of cardiac tissue. After demonstrating optical stimulation of larval heart rate, the approach was tested at low temperature and low calcium levels to simulate mammalian heart transplant conditions. Optical activation of ChR2.XXL substantially increased heart rate in all conditions. We have developed a system that can be instrumental in characterizing the physiology of optogenetically controlled cardiac function with an intact heart. PMID- 26834238 TI - PAQR3 controls autophagy by integrating AMPK signaling to enhance ATG14L associated PI3K activity. AB - The Beclin1-VPS34 complex is recognized as a central node in regulating autophagy via interacting with diverse molecules such as ATG14L for autophagy initiation and UVRAG for autophagosome maturation. However, the underlying molecular mechanism that coordinates the timely activation of VPS34 complex is poorly understood. Here, we identify that PAQR3 governs the preferential formation and activation of ATG14L-linked VPS34 complex for autophagy initiation via two levels of regulation. Firstly, PAQR3 functions as a scaffold protein that facilitates the formation of ATG14L- but not UVRAG-linked VPS34 complex, leading to elevated capacity of PI(3)P generation ahead of starvation signals. Secondly, AMPK phosphorylates PAQR3 at threonine 32 and switches on PI(3)P production to initiate autophagosome formation swiftly after glucose starvation. Deletion of PAQR3 leads to reduction of exercise-induced autophagy in mice, accompanied by a certain degree of disaggregation of ATG14L-associated VPS34 complex. Together, this study uncovers that PAQR3 can not only enhance the capacity of pro-autophagy class III PI3K due to its scaffold function, but also integrate AMPK signal to activation of ATG14L-linked VPS34 complex upon glucose starvation. PMID- 26834241 TI - The role of autologous stem cell transplantation in primary central nervous system lymphoma. AB - Primary central nervous system lymphoma (PCNSL) treatment includes 2 phases: induction and consolidation. Induction consists of high-dose methotrexate-based polychemotherapy for most patients, with regimen and dose variations according to patient characteristics and country. Several strategies have been proposed for the consolidation phase, with whole-brain irradiation (WBRT) the most common. However, some authorities recommend avoiding WBRT because of its related risk of severe neurotoxicity. The most relevant alternatives to WBRT are high-dose chemotherapy supported by autologous stem cell transplantation (HDC/ASCT) or nonmyeloablative chemotherapy, the former supported by several single-arm phase 2 trials. Moreover, HDC/ASCT is the only strategy that is assessed in comparison with WBRT in ongoing randomized trials. The rationale for using HDC/ASCT in PCNSL patients is based on the fact that the delivery of high doses could achieve therapeutic drug concentrations in the brain and cerebrospinal fluid, and that non-cross-resistant drugs used for conditioning (eg, alkylating agents) could favor elimination of residual chemoresistant lymphoma cells. Worldwide experience with HDC/ASCT is limited to few single-arm phase 2 trials, but overall results are encouraging, mostly when thiotepa-containing conditioning regimens are used, both in newly diagnosed and relapsed patients. However, several questions on efficacy and feasibility of HDC/ASCT, as well as the best candidates for this strategy, the optimal conditioning regimen, the best time for response assessment, and acute and late effects, remain unanswered. In this review, we critically analyze reported studies on HDC/ASCT in PCNSL and discuss its current role and future perspectives in treating this aggressive malignancy. PMID- 26834239 TI - Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors. AB - The Gata2 transcription factor is a pivotal regulator of hematopoietic cell development and maintenance, highlighted by the fact that Gata2 haploinsufficiency has been identified as the cause of some familial cases of acute myelogenous leukemia/myelodysplastic syndrome and in MonoMac syndrome. Genetic deletion in mice has shown that Gata2 is pivotal to the embryonic generation of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). It functions in the embryo during endothelial cell to hematopoietic cell transition to affect hematopoietic cluster, HPC, and HSC formation. Gata2 conditional deletion and overexpression studies show the importance of Gata2 levels in hematopoiesis, during all developmental stages. Although previous studies of cell populations phenotypically enriched in HPCs and HSCs show expression of Gata2, there has been no direct study of Gata2 expressing cells during normal hematopoiesis. In this study, we generate a Gata2Venus reporter mouse model with unperturbed Gata2 expression to examine the hematopoietic function and transcriptome of Gata2 expressing and nonexpressing cells. We show that all the HSCs are Gata2 expressing. However, not all HPCs in the aorta, vitelline and umbilical arteries, and fetal liver require or express Gata2. These Gata2-independent HPCs exhibit a different functional output and genetic program, including Ras and cyclic AMP response element-binding protein pathways and other Gata factors, compared with Gata2-dependent HPCs. Our results, indicating that Gata2 is of major importance in programming toward HSC fate but not in all cells with HPC fate, have implications for current reprogramming strategies. PMID- 26834240 TI - Bleomycin in older early-stage favorable Hodgkin lymphoma patients: analysis of the German Hodgkin Study Group (GHSG) HD10 and HD13 trials. AB - Doxorubicin, bleomycin, vinblastine sulfate, and dacarbazine (ABVD) is associated with severe toxicity in older patients, particularly from bleomycin-induced lung toxicity (BLT). Therefore, using bleomycin has been questioned in older Hodgkin lymphoma (HL) patients, especially in early-stage HL. We therefore analyzed feasibility, toxicity, and efficacy of ABVD or AVD in 287 older early-stage favorable HL patients. We included patients >=60 years of age in the German Hodgkin Study Group HD10 and HD13 trials randomized to either 2 cycles of ABVD (2*ABVD; n = 137) or AVD (2*AVD; n = 82), each followed by involved-field radiotherapy (IF-RT), with patients randomized to 4*ABVD+IF-RT (n = 68). Patients' median age was 65 years (range, 60-75) with comparable patient and disease characteristics. Grade III-IV adverse event rates were similar in patients receiving 2*AVD and 2*ABVD (40% and 39%, respectively), but considerably higher in patients receiving 4*ABVD (65%). Similarly, BLT was rare in patients receiving 2*ABVD/AVD, but occurred in 7/69 (10%) of patients randomized to 4*ABVD, with 3 lethal events. In conclusion, no effects of bleomycin on toxicity rates were detectable in older patients receiving 2 cycles of chemotherapy. However, we found a high risk of severe toxicity of bleomycin in older HL patients receiving more than 2 cycles of ABVD. These trials are registered at www.clinicaltrials.gov and www.isrctn.com as #NCT00265018 (HD10) and #ISRCTN63474366 (HD13). PMID- 26834243 TI - GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo. AB - Acute myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy, which is initiated and driven by a rare fraction of leukemia stem cells (LSCs). Despite the difficulties of identifying a common LSC phenotype, there is increasing evidence that high expression of stem cell gene signatures is associated with poor clinical outcome. Identification of functionally distinct subpopulations in this disease is therefore crucial to dissecting the molecular machinery underlying LSC self-renewal. Here, we combined next-generation sequencing technology with in vivo assessment of LSC frequencies and identified the adhesion G protein-coupled receptor 56 (GPR56) as a novel and stable marker for human LSCs for the majority of AML samples. High GPR56 expression was significantly associated with high-risk genetic subgroups and poor outcome. Analysis of GPR56 in combination with CD34 expression revealed engraftment potential of GPR56(+)cells in both the CD34(-)and CD34(+)fractions, thus defining a novel LSC compartment independent of the CD34(+)CD38(-)LSC phenotype. PMID- 26834242 TI - Impact of dual expression of MYC and BCL2 by immunohistochemistry on the risk of CNS relapse in DLBCL. AB - Dual expression of MYC and BCL2 by immunohistochemistry (IHC) is associated with poor outcome in diffuse large B-cell lymphoma (DLBCL). Dual translocation of MYC and BCL2, so-called "double-hit lymphoma," has been associated with a high risk of central nervous system (CNS) relapse; however, the impact of dual expression of MYC and BCL2 (dual expressers) on the risk of CNS relapse remains unknown. Pretreatment formalin-fixed paraffin-embedded DLBCL biopsies derived from patients subsequently treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were assembled on tissue microarrays from 2 studies and were evaluated for expression of MYC and BCL2 by IHC. In addition, cell of origin was determined by IHC and the Lymph2Cx gene expression assay in a subset of patients. We identified 428 patients who met the inclusion criteria. By the recently described CNS risk score (CNS-International Prognostic Index [CNS IPI]), 34% were low risk (0 to 1), 45% were intermediate risk (2 to 3), and 21% were high risk (4 or greater). With a median follow-up of 6.8 years, the risk of CNS relapse was higher in dual expressers compared with non-dual expressers (2 year risk, 9.7% vs 2.2%; P = .001). Patients with activated B-cell or non germinal center B-cell type DLBCL also had an increased risk of CNS relapse. However, in multivariate analysis, only dual expresser status and CNS-IPI were associated with CNS relapse. Dual expresser MYC(+) BCL2(+) DLBCL defines a group at high risk of CNS relapse, independent of CNS-IPI score and cell of origin. Dual expresser status may help to identify a high-risk group who should undergo CNS-directed evaluation and consideration of prophylactic strategies. PMID- 26834244 TI - US panel recommends depression screening for all adults. PMID- 26834245 TI - Detection of ductal carcinoma in situ and subsequent interval cancers. PMID- 26834246 TI - Abortion in Northern Ireland: is change on the cards? PMID- 26834247 TI - Pneumococcal Vaccination Strategies in the Real World of Chronically Ill Patients. PMID- 26834248 TI - MCID - The Minimal Clinically Important Difference Assigns Significance to Outcome Effects. PMID- 26834249 TI - A Portrait of Juvenile Arthritis with Multiple Joint Abnormalities. PMID- 26834250 TI - Facial Rash following Infliximab Treatment. PMID- 26834251 TI - What Is the Significance of Change of Cutpoint from 13 to 12 If Polysymptomatic Distress Is Not a Diagnostic Criterion? PMID- 26834252 TI - Dr. Wolfe replies. PMID- 26834253 TI - The Polysymptomatic Distress Scale Is Simple, Useful, and Effective in Clinical Care and Clinical and Epidemiology Studies. PMID- 26834254 TI - Drs. Friend and Bennett reply. PMID- 26834255 TI - A Fatal Case of Calciphylaxis in a Patient with Systemic Lupus Erythematosus and Normal Renal Function. PMID- 26834256 TI - Cytomegalovirus-induced Colon Perforation in Systemic Lupus Erythematosus. PMID- 26834257 TI - An Unexpected Cause of Tenosynovitis. PMID- 26834258 TI - Higher Prevalence of Metabolic Syndrome in Patients with Psoriatic Arthritis: A Comparison with a Control Group of Noninflammatory Rheumatologic Conditions. PMID- 26834259 TI - The Role of Altruistic Values in Motivating Underrepresented Minority Students for Biomedicine. AB - Understanding how cultural values influence undergraduate students' science research experiences and career interest is important in efforts to broaden participation and to diversify the biomedical research workforce. The results from our prospective longitudinal study demonstrated that underrepresented minority student (URM) research assistants who see the altruistic value of conducting biomedical research feel more psychologically involved with their research over time, which, in turn, enhances their interest in pursuing a scientific research career. These altruistic motives are uniquely influential to URM students and appear to play an important role in influencing their interest in scientific research careers. Furthermore, seeing how research can potentially affect society and help one's community does not replace typical motives for scientific discovery (e.g., passion, curiosity, achievement), which are important for all students. These findings point to simple strategies for educators, training directors, and faculty mentors to improve retention among undergraduate URM students in biomedicine and the related sciences. PMID- 26834260 TI - Treatment of Fish--A Comment. PMID- 26834261 TI - Should we be more concerned about bovine leukemia virus? PMID- 26834262 TI - An ethicist's commentary on referring cases to competing practices. PMID- 26834263 TI - Total cysto-prostatectomy: Technique description and results in 2 dogs. AB - We describe a novel technique for total cysto-prostatectomy, followed by uretero urethral anastomosis in 2 dogs. The technique was successful and was performed without pubic osteotomy. Post-operative urinary tract infections may be a potentially serious event. PMID- 26834264 TI - Pneumonia and gastritis in a cat caused by feline herpesvirus-1. AB - We report a case of fatal respiratory and gastric herpesvirus infection in a vaccinated, adult cat with no known immunosuppression or debilitation. The disease was characterized by severe necrotizing bronchopneumonia, fibrinonecrotic laryngotracheitis, and multifocal necrotizing gastritis associated with eosinophilic intranuclear inclusion bodies and a large amount of feline herpesvirus-1 antigen detected with immunohistochemistry. PMID- 26834265 TI - Acute fatal pericardial effusion induced by accidental ingestion of cigarette butts in a dog. AB - A dog was referred for collapse and tachypnea after ingesting cigarette butts. Thoracic radiography and echocardiography indicated pericardial effusion, and an electrocardiogram showed tachycardia, variable QRS complexes, and ventricular premature complexes. This is the first description of fatal pericardial effusion associated with cigarette butt ingestion in a veterinary patient. PMID- 26834266 TI - Bilateral laryngeal paralysis in a dog secondary to laryngeal osseous metaplasia. AB - A 7-year-old spayed female Lurcher was evaluated for a chronic history of increased upper respiratory noise. Advanced imaging including digital radiography and pre- and post-contrast computed tomography (CT) scan confirmed the presence of an ill-defined soft tissue mineralized mass of the ventral larynx. Histopathology demonstrated pleocellular myositis and fasciitis with osseous metaplasia. PMID- 26834267 TI - Survey of gastrointestinal nematode parasites in Saskatchewan beef herds. AB - A survey of gastrointestinal parasites in Saskatchewan beef herds was conducted over the summer of 2014. Fecal samples were collected on 3 occasions during the summer grazing season from beef cows and calves from 14 herds. The mean number of strongylid eggs per gram of feces recovered from calves increased 9-fold (95% CI: 4.5 to 18) over the summer period, while egg counts in the cows remained constant over the same period. The prevalence and infection intensities of gastrointestinal nematode parasites in cow-calf herds in Saskatchewan were comparable to what is seen in cattle grazing in the northern regions of the United States and for which anthelmintic treatments have resulted in positive production benefits. PMID- 26834268 TI - Comparison of an alcohol-based hand rub and water-based chlorhexidine gluconate scrub technique for hand antisepsis prior to elective surgery in horses. AB - This prospective clinical study evaluates the effectiveness of an alcohol-based hand rub (AvagardTM) for pre-surgical hand antisepsis in an equine hospital and compares it with traditional scrubbing technique using 4% chlorhexidine gluconate sponges and water. Prior to elective surgery, 3 board-certified surgeons were randomly assigned to hand antisepsis with either technique. Culture samples of each hand were taken at 4 times: before and after neutral soap hand wash, after scrub or rubbing technique, and after surgery. There was no significant difference in mean bacterial colony forming units between scrub and rub techniques over the 3 time periods (P = 0.6), controlling for initial counts. One horse from the scrub group had a skin incision infection following stifle arthroscopy; this was resolved with medical treatment. The alcohol-based hand rub is equivalent in efficacy for pre-surgical hand antisepsis to traditional water based scrubs in an equine hospital setting. PMID- 26834269 TI - Prevalence of paratuberculosis in the dairy goat and dairy sheep industries in Ontario, Canada. AB - A cross-sectional study was undertaken (October 2010 to August 2011) to estimate the prevalence of paratuberculosis in the small ruminant dairy industries in Ontario, Canada. Blood and feces were sampled from 580 goats and 397 sheep (lactating and 2 y of age or older) that were randomly selected from 29 randomly selected dairy goat herds and 21 convenience-selected dairy sheep flocks. Fecal samples were analyzed using bacterial culture (BD BACTEC MGIT 960) and polymerase chain reaction (Tetracore); serum samples were tested with the Prionics Parachek enzyme-linked immunosorbent assay (ELISA). Using 3-test latent class Bayesian models, true farm-level prevalence was estimated to be 83.0% [95% probability interval (PI): 62.6% to 98.1%] for dairy goats and 66.8% (95% PI: 41.6% to 91.4%) for dairy sheep. The within-farm true prevalence for dairy goats was 35.2% (95% PI: 23.0% to 49.8%) and for dairy sheep was 48.3% (95% PI: 27.6% to 74.3%). These data indicate that a paratuberculosis control program for small ruminants is needed in Ontario. PMID- 26834270 TI - Hypersensitivity reactions associated with L-asparaginase administration in 142 dogs and 68 cats with lymphoid malignancies: 2007-2012. AB - Clinically significant hypersensitivity reactions (HSRs) to the chemotherapy drug L-asparaginase are reported in humans and dogs, but frequency in small animals is not well-defined. This study retrospectively evaluated the frequency of HSR to L asparaginase given by IM injection to dogs and cats with lymphoid malignancies. The medical records of all dogs and cats treated with at least 1 dose of L asparaginase chemotherapy over a 5-year period were reviewed. A total of 370 doses of L-asparaginase were administered to the dogs, with 88 of 142 dogs receiving multiple doses, and 6 dogs experiencing an HSR. A total of 197 doses were administered to the cats, with 33 of 68 cats receiving multiple doses, and no cats experiencing an HSR. Hypersensitivity reactions were documented in 4.2% of dogs, and in association with 1.6% of L-asparaginase doses administered. These results show that HSRs occur uncommonly among dogs and cats, even with repeated dosing. PMID- 26834271 TI - Bacterial probiotics as an aid in the control of Clostridium difficile disease in neonatal pigs. AB - Although Clostridium difficile infection (CDI) is a common disease in swine, there is a lack of prevention strategies. The objectives of this study were to evaluate: i) the effectiveness of Lactobacillus spp. and ii) non-toxigenic C. difficile (NTCD) as prevention for the development of CDI in piglets. Cesarean derived piglets (N = 150) were randomly assigned to 6 groups: GROUP 1 - negative control (n = 10); GROUP 2 - NTCD only (n = 13); GROUP 3 - Lactobacillus spp. only (n = 14); GROUP 4 - positive control (challenged with toxigenic C. difficile strain) (n = 35); GROUP 5 - NTCD and challenged with the toxigenic C. difficile strain (n = 34); and GROUP 6 - Lactobacillus spp. and challenged with the toxigenic C. difficile strain (n = 44). Piglets which received NTCD showed lower prevalence of toxin-positive feces, mesocolonic edema, and microscopic lesions compared with positive control piglets. Administration of Lactobacillus spp. did not reveal clear benefits. PMID- 26834272 TI - A novel dextran polymer hydrogel local antimicrobial therapy in dogs: A pilot study. AB - Our purpose was to evaluate physical, laboratory, and/or radiographic abnormalities associated with a novel dextran polymer hydrogel local antimicrobial agent impregnated with amikacin and clindamycin in dogs having tibial plateau leveling osteotomy implants removed due to suspected surgical site infection. A total of 28 client-owned dogs were enrolled and 20 completed the study. Routine plate explantation and bacterial cultures were performed and the polymer hydrogel was applied to the surgery site. No systemic antimicrobials were used after surgery. Serum biochemistry, hematology, urinalysis, physical examinations, and radiographs were monitored before surgery and up to 12 wk after surgery. Sixteen of the 20 dogs (80%) had a positive bacterial culture, 44% of which were methicillin resistant. There were no significant alterations of laboratory values, physical examination, or radiographs to indicate adverse reactions to the polymer hydrogel. There were no signs of inflammation or infection in any patient at the 12-week postoperative recheck. PMID- 26834274 TI - Juvenile cellulitis in a 7-week-old golden retriever dog. AB - A 7-week-old golden retriever puppy was presented with acute onset of marked facial inflammation and pustular dermatitis, markedly enlarged submandibular lymph nodes, and pyrexia. Treatment included high-dose corticosteroids and antibiotics. One week after presentation the puppy showed a significant decrease in inflammation and healing pustules. PMID- 26834276 TI - The challenge of nonsurgical and nonmedical communication. PMID- 26834275 TI - Canine superficial pyoderma and therapeutic considerations. PMID- 26834273 TI - Evaluation of 21 426 feline bladder urolith submissions to the Canadian Veterinary Urolith Centre (1998-2014). AB - This study reports emerging trends in feline urolithiasis in Canada during the past 16.8 y, evaluates associations of breed and gender with urolith types, and reports on feline submissions from outside of Canada. Struvite and calcium oxalate uroliths comprised > 90% of all uroliths submitted. In cats, oxalate submissions outnumbered struvite submissions from Canada, Hong Kong, Denmark, and the United Arab Emirates, while Australian struvite submissions outnumbered calcium oxalate submissions. In Canada, the majority of urolith submissions were from domestic cats followed by Himalayan, Persian, and Siamese cats. Males were more likely to form calcium oxalate uroliths and females were more likely to develop struvite uroliths. Compared to domestic short-haired cats, Tonkinese, Burmese, Devon rex, Himalayan, Persian, and Siamese cats were significantly associated with calcium oxalate urolith submission. Egyptian mau, Birman, ocicat, and Siamese breeds were over-represented amongst urate submissions. PMID- 26834277 TI - Electrochemical behavior of bioactive coatings on cp-Ti surface for dental application. AB - The surface characteristics and electrochemical properties of bioactive coatings produced by plasma electrolytic oxidation (PEO) with calcium, phosphorous, silicon and silver on commercially pure titanium were evaluated. PEO treatment produced a porous oxide layer, which improved the surface topography, and enriched the surface chemistry with bioactive elements, responsible for mimicking bone surface. The surfaces with higher calcium concentration presented antibacterial and biocompability properties with better responses for corrosion and barrier properties, due to the presence of rutile crystalline structure. PEO may be a promising surface treatment option to improve the electrochemical behavior of dental implants mitigating treatment failures. PMID- 26834278 TI - An approach to mental health in low and middle income countries: a case example from urban India. AB - Women in low and middle income countries (LMICs) facing poverty, challenging living conditions and gender inequality often express their emotional difficulties through physical health concerns and seek care at primary health facilities. However, primary care providers in LMICs only treat the physical health symptoms and lack appropriate services to address women's mental health problems. This paper, presents data from the counseling component of a multilevel, research and intervention project in a low income community in Mumbai, India whose objective was to improve sexual health and reduce HIV/STI risk among married women. Qualitative data from counselor notes shows that poor mental health, associated with negative and challenging life situations, is most often expressed by women as gynecological concerns through the culturally-based syndrome of tenshun. A path analysis was conducted on baseline quantitative data that confirmed the relationships between sources of tenshum, emotional status and symptoms of common mental disorders (CMDs). Based on these findings, the authors propose a need for culturally appropriate primary care services for LMICs that would integrate mental and physical health. This approach would reduce mental health morbidity among women through early intervention and prevention of the development of CMDs. PMID- 26834279 TI - Challenges and Rewards of Conducting Research on Recovery Residences for Alcohol and Drug Disorders. AB - Although research shows treatment for alcohol and drug problems can be effective, persons without stable housing that supports recovery are at risk for relapse. Recovery residences (RRs) for drug and alcohol problems are a growing response to the need for alcohol- and drug-free living environments that support sustained recovery. Research on RRs offers an opportunity to examine how integration of these individuals into a supportive, empowering environment has beneficial impacts on substance use, housing, and other outcomes, as well as benefits for the surrounding community. Research can also lead to the identification of operations and practices within houses that maximize favorable outcomes for residents. However, research on RRs also presents significant obstacles and challenges. Based on our experiences conducting recovery home research for decades, we present suggestions for addressing some of the unique challenges encountered in this type of research. PMID- 26834281 TI - Tribute: Jeri L. Dobbs: 1935-2015. PMID- 26834280 TI - From the Editor: Make the Most of Every Interaction. PMID- 26834282 TI - Comparison of Warm Blood Cardioplegia Delivery With or Without the Use of a Roller Pump. AB - Various techniques for administration of blood cardioplegia are used worldwide. In this study, the effect of warm blood cardioplegia administration with or without the use of a roller pump on perioperative myocardial injury was studied in patients undergoing coronary artery bypass grafting using minimal extra corporeal circuits (MECCs). Sixty-eight patients undergoing elective coronary bypass surgery with an MECC system were consecutively enrolled and randomized into a pumpless group (PL group: blood cardioplegia administration without roller pump) or roller pump group (RP group: blood cardioplegia administration with roller pump). No statistically significant differences were found between the PL group and RP group regarding release of cardiac biomarkers. Maximum postoperative biomarker values reached at T1 (after arrival intensive care unit) for heart-type fatty acid binding protein (2.7 [1.5; 6.0] ng/mL PL group vs. 3.2 [1.6; 6.3] ng/mL RP group, p = .63) and at T3 (first postoperative day) for troponin T high sensitive (22.0 [14.5; 29.3] ng/L PL group vs. 21.1 [15.3; 31.6] ng/L RP group, p = .91), N-terminal pro-brain natriuretic peptide (2.1 [1.7; 2.9] ng/mL PL group vs. 2.6 [1.6; 3.6] ng/mL RP group, p = .48), and C-reactive protein (138 [106; 175] MUg/mL PL group vs. 129 [105; 161] MUg/mL RP group, p = .65). Besides this, blood cardioplegia flow, blood cardioplegia line pressure, and aortic root pressure during blood cardioplegia administration were similar between the two groups. Administration of warm blood cardioplegia with or without the use of a roller pump results in similar clinically acceptable myocardial protection. PMID- 26834283 TI - Survival Following Veno-Venous Extracorporeal Membrane Oxygenation and Mortality in a Diverse Patient Population. AB - Racial and ethnic disparities in cardiovascular disease are well established; however, there is limited information about survival differences following veno venous extracorporeal membrane oxygenation (VV-ECMO) in contemporary adult populations. The purpose of this study was to assess survival at discharge, 30 days, and at 1 year following institution of VV-ECMO in an ethnically diverse population, and to examine potential risk factors for mortality. This was a single-center study of 41 patients (49% female, 27% minorities, 7% > 65 years) who received VV-ECMO between the years 2004 and 2013 at an academic medical center. Kaplan-Meier estimates were calculated to assess survival up to 1 year, and cox proportional hazard models were used to evaluate the association between risk factors, mortality, and confounders. Overall, 76% (n = 31) of VV-ECMO patients survived to discharge and 30 days and 71% (n = 29) survived to 1 year. Whites (n = 30) had a higher survival at 1 year compared to minorities (n = 11) (83% vs. 36%, respectively, p = .01). Minorities had a significantly increased risk of mortality at 30 days (hazard ratio [HR] = 5.07, 95% confidence interval [CI] = 1.42-18.09) and at 1 year (HR = 5.19, 95% CI = 1.63-16.55). Race/ethnicity remained a significant independent predictor of survival at 30 days except when history of shock or lung transplantation was included in adjusted regression models. VV-ECMO was associated with an excellent overall survival up to 1 year. Racial/ethnic minorities had a 5-fold increased risk for 30-day mortality, which was largely explained by a lower likelihood of lung transplantation and increased risk of shock. PMID- 26834284 TI - Factor V Leiden and Cardiopulmonary Bypass. AB - We present a case of a patient with factor V Leiden with an antithrombin III activity of 67% who received a successful aortic valve replacement supported by cardiopulmonary bypass (CPB). A safe level of anticoagulation was achieved by monitoring activated clotting time (ACT) and heparin concentration ensuring adequate anticoagulation throughout the procedure. Results from ACT, heparin dose response, heparin protamine titration, and thrombelastography are given. Factor V Leiden patients can be safely anti-coagulated using heparin for CPB procedures when monitored with ACT, heparin protamine titration, and thrombelastography. Postoperative chest tube losses were 360 mL, less than half our institutional average. Anticoagulation for the pre-and post-operative phase is also discussed. PMID- 26834285 TI - Chronic Severe Hyponatremia and Cardiopulmonary Bypass: Avoiding Osmotic Demyelination Syndrome. AB - Serum sodium concentration affects every cell in the body with respect to cellular tonicity. Hyponatremia is the most frequent electrolyte abnormality encountered, occurring at clinical admission in 22% of elderly patients. Any rapid correction of chronic severe hyponatremia can result in rapid cellular shrinking due to loss of intracellular free water. This is commonly associated with paralysis and severe brain damage due to osmotic demyelination syndrome (ODS). ODS occurs because the body has the ability to compensate for cellular fluid shifts due to chronic hyponatremia (by a decrease in brain concentration of several ions, amino acids, and organic osmolytes). Thus, the neurons are often at a functional state of fluid balance despite the sodium imbalance. The initiation of cardiopulmonary bypass (CPB) can introduce between 1 and 2 L of priming solution containing a normal sodium concentration creating a rapid rise in sodium concentration within the extracellular fluid. This abrupt change establishes a situation where intracellular free water can be lost resulting in cellular shrinking and ODS. In presenting this case study, we hope to add to the current literature with a specific isotonic approach to treating the chronically severe hyponatremic patient pre-CPB, during CPB, and post-CPB. PMID- 26834286 TI - Heart Failure in Thyrotoxic Cardiomopathy: Extracorporeal Membrane Oxygenation Treatment for Graves' Disease. AB - Thyrotoxicosis-induced cardiomyopathy and consequent heart failure is one of the most grave complications of uncontrolled hyperthyroidism. In such patients, early recognition of thyrotoxicosis, and directed antithyroid therapy can lead to rapid normalization of left ventricular function. Herein, we present a case of a 29 year-old male with Graves' disease who developed heart failure with severe deterioration of left ventricular function and eventually, circulatory collapse. Height and weight of the patient were 1.8 m and 84 kg, respectively. The patient was placed on venoarterial extracorporeal membrane oxygenation for immediate circulatory support, with restoration of cardiac function after 6 days. PMID- 26834287 TI - Apicoaortic Valve Conduit for a Patient with Aortic Valve Stenosis and Patent Coronary Bypass Grafts Using Cardiopulmonary Bypass. AB - In adults over 65 years of age, aortic valve stenosis has been found to be present in 2-9% within this group. Furthermore, aortic valve replacements in patients whom have had a previous coronary artery bypass grafting surgery have a mortality rate as high as 18%. A non-conventional effective surgical approach of bypassing the aortic valve by inserting an apicoaortic valve conduit (AVC) connecting the left ventricular apex to the descending thoracic aorta has been previously documented. We describe the case of a successful implantation of an AVC in a 64-year-old Caucasian male using cardiopulmonary bypass. PMID- 26834288 TI - Perfusion Electronic Record Documentation Using Epic Systems Software. AB - This paper describes the design and use of Epic Systems software for documentation of perfusion activities as part of the patient electronic medical record. The University of Wisconsin Hospital and Clinics adapted the Anesthesia software module and developed an integrated perfusion/anesthesia record for the documentation of cardiac and non-cardiac surgical procedures. This project involved multiple committees, approvals, and training to successfully implement. This article will describe our documentation options, concepts, design, challenges, training, and implementation during our initial experience. PMID- 26834289 TI - Perfusion Electronic Record Documentation Using Epic Systems Software. AB - The authors comment on Steffens and Gunser's article describing the University of Wisconsin adoption of the Epic anesthesia record to include perfusion information from the cardiopulmonary bypass patient experience. We highlight the current-day lessons and the valuable quality and safety principles the Wisconsin-Epic model anesthesia-perfusion record provides. PMID- 26834290 TI - Emergent Cardiopulmonary Bypass during Cardiac Surgery. AB - During orientation to the cardiac surgery operating room, new staff may not be exposed to emergent situations. Allowing team members the opportunity to practice their roles during less common, high-stakes emergency cardiac surgical scenarios may better prepare them when crises do arise in the OR. The Emergency Cardiopulmonary Bypass Course was developed to meet the needs of new staff starting in cardiac surgery. Recently, the course has expanded to include experienced staff. This communication describes a high fidelity simulation based course that includes four emergent cardiac surgery scenarios. PMID- 26834291 TI - Erratum. AB - [This corrects the article on p. 83 in vol. 47, PMID: 26405355.]. PMID- 26834293 TI - Instituting a filtration/pressurization system to reduce dust concentrations in a control room at a mineral processing plant. AB - The National Institute for Occupational Safety and Health has observed that many control rooms and operator compartments in the U.S. mining industry do not have filtration systems capable of maintaining low dust concentrations in these areas. In this study at a mineral processing plant, to reduce respirable dust concentrations in a control room that had no cleaning system for intake air, a filtration and pressurization system originally designed for enclosed cabs was modified and installed. This system was composed of two filtering units: one to filter outside air and one to filter and recirculate the air inside the control room. Eighty-seven percent of submicrometer particles were reduced by the system under static conditions. This means that greater than 87 percent of respirable dust particles should be reduced as the particle-size distribution of respirable dust particles is greater than that of submicrometer particles, and filtration systems usually are more efficient in capturing the larger particles. A positive pressure near 0.02 inches of water gauge was produced, which is an important component of an effective system and minimizes the entry of particles, such as dust, into the room. The intake airflow was around 118 cfm, greater than the airflow suggested by the American Society of Heating, Refrigerating, and Air Conditioning Engineers (ASHRAE) for acceptable indoor air quality. After one year, the loading of the filter caused the airflow to decrease to 80 cfm, which still produces acceptable indoor air quality. Due to the loading of the filters, the reduction efficiency for submicrometer particles under static conditions increased to 94 percent from 87 percent. PMID- 26834294 TI - A general, enantioselective synthesis of N-alkyl terminal aziridines and C2 functionalized azetidines via organocatalysis. AB - A short, high-yielding protocol involving the enantioselective alpha-chlorination of aldehydes has been developed for the enantioselective synthesis of C2 functionalized aziridines and N-alkyl terminal azetidines from a common intermediate. This methodology allows for the rapid preparation of functionalized aziridines in 50-73% overall yields and 88-94% ee, and azetidines in 22-32% overall yields and 84-92% ee. Moreover, we developed a scalable and cost effective route to the key organocatalyst (54% overall yield, >95% dr). PMID- 26834295 TI - Nonenzymatic enantioselective synthesis of all-carbon quaternary centers through desymmetrization. AB - The asymmetric desymmetrization of meso or prochiral compounds containing an all carbon quaternary center is an attractive alternative to classical synthetic approaches aimed at the asymmetric formation of a new C-C bond. This review focuses on nonenzymatic desymmetrizations that utilize transition metal catalysts or organocatalysts to distinguish between enantiotopic groups to generate enantioenriched compounds containing all-carbon quaternary stereocenters. PMID- 26834296 TI - BEYOND TEXT: USING ARRAYS TO REPRESENT AND ANALYZE ETHNOGRAPHIC DATA. AB - Recent methodological debates in sociology have focused on how data and analyses might be made more open and accessible, how the process of theorizing and knowledge production might be made more explicit, and how developing means of visualization can help address these issues. In ethnography, where scholars from various traditions do not necessarily share basic epistemological assumptions about the research enterprise with either their quantitative colleagues or one another, these issues are particularly complex. Nevertheless, ethnographers working within the field of sociology face a set of common pragmatic challenges related to managing, analyzing, and presenting the rich context-dependent data generated during fieldwork. Inspired by both ongoing discussions about how sociological research might be made more transparent, as well as innovations in other data-centered fields, the authors developed an interactive visual approach that provides tools for addressing these shared pragmatic challenges. They label the approach "ethnoarray" analysis. This article introduces this approach and explains how it can help scholars address widely shared logistical and technical complexities, while remaining sensitive to both ethnography's epistemic diversity and its practitioners shared commitment to depth, context, and interpretation. The authors use data from an ethnographic study of serious illness to construct a model of an ethnoarray and explain how such an array might be linked to data repositories to facilitate new forms of analysis, interpretation, and sharing within scholarly and lay communities. They conclude by discussing some potential implications of the ethnoarray and related approaches for the scope, practice, and forms of ethnography. PMID- 26834297 TI - Framing a socio-indexical basis for the emergence and cultural transmission of phonological systems. AB - Moulin-Frier et al. (2016) proffer a conceptual framework and computational modeling architecture for the investigation of the emergence of phonological universals for spoken languages. They validate the framework and architecture by testing to see whether universals such as the prevalence of triangular vowel systems that show adequate dispersion in the F1-F2-F3 space can fall out of simulations of referential communication between social agents, without building principles such as dispersion directly into the model. In this paper, we examine the assumptions underlying the framework, beginning with the assumption that it is such substantive universals that are in need of explanation rather than the rich diversity of phonological systems observed across human cultures and the compositional ("prosodic") structure that characterizes signed as well as spoken languages. Also, when emergence is construed at the time-scales of the biological evolution of the species and of the cultural evolution of distinct speech communities, it is the affiliative or affective rather than the referential function that has the greater significance for our understanding of how phonological systems can emerge de novo in ontogeny. PMID- 26834292 TI - Mercury, selenium and fish oils in marine food webs and implications for human health. AB - Humans who eat fish are exposed to mixtures of healthful nutrients and harmful contaminants that are influenced by environmental and ecological factors. Marine fisheries are composed of a multitude of species with varying life histories, and harvested in oceans, coastal waters and estuaries where environmental and ecological conditions determine fish exposure to both nutrients and contaminants. Many of these nutrients and contaminants are thought to influence similar health outcomes (i.e., neurological, cardiovascular, immunological systems). Therefore, our understanding of the risks and benefits of consuming seafood require balanced assessments of contaminants and nutrients found in fish and shellfish. In this paper, we review some of the reported benefits of fish consumption with a focus on the potential hazards of mercury exposure, and compare the environmental variability of fish oils, selenium and mercury in fish. A major scientific gap identified is that fish tissue concentrations are rarely measured for both contaminants and nutrients across a range of species and geographic regions. Interpreting the implications of seafood for human health will require a better understanding of these multiple exposures, particularly as environmental conditions in the oceans change. PMID- 26834298 TI - Adolescents' Educational Outcomes in a Social Ecology of Parenting, Family, and Community Risks in Northern Ireland. AB - This study examines the influence of social ecological risks within the domains of parenting, family environment, and community in the prediction of educational outcomes for 770 adolescents (49% boys, 51% girls, M = 13.6 years, SD = 2.0) living in a setting of protracted political conflict, specifically working class areas of Belfast, Northern Ireland. Controlling for religious community, age, and gender, youths' lower academic achievement was associated with family environments characterized by high conflict and low cohesion. School ehaviour problems were related to greater exposure to community violence, or sectarian and nonsectarian antisocial behaviour. Youths' expectations about educational attainment were undermined by conflict in the family environment and antisocial behaviour in the community, as well as parenting low in warmth and behavioural control. Findings underscore the importance of considering family and community contributions to youths' educational outcomes. Suggestions regarding targeted interventions toward promoting resilience are discussed, such as assessing both child and family functioning, developing multidimensional interventions for parents, and building community partnerships, among others. PMID- 26834299 TI - The Interactive Effects of the Capability for Suicide and Major Depressive Episodes on Suicidal Behavior in a Military Sample. AB - Major depressive symptoms represent a significant risk for suicidal ideation and behavior. Given that suicide is fearsome, the interpersonal theory of suicide proposes that individuals who engage in suicidal behavior possess not only the desire to die, but also the acquired capability (AC) for suicide. This study examined whether major depressive episodes (MDEs) may be particularly relevant to suicidal behavior when considered in the context of AC. History of MDEs, AC, and suicide attempt history were examined in a large (n=3,377) sample of military members. Data were analyzed using hierarchical multiple regression. Results indicated that among individuals with high AC, the number of MDEs was significantly, positively associated with number of previous suicide attempts; MDEs were not significantly related to suicide attempt history among individuals with low AC. Findings held in the presence of robust covariates associated with suicidal behavior. Findings suggest that a history of MDEs alone may not indicate severe suicide risk - increased AC for suicide appears necessary for increased suicide risk. Implications for suicide treatment and prevention in military personnel are discussed. PMID- 26834301 TI - Children's Hyperactivity, Television Viewing, and The Potential for Child Effects. AB - Using data from the Early Childhood Longitudinal Study-Birth Cohort (ECLS-B; n = 6,250), this study examined whether children who display difficult behaviors early in life watch more television from year-to-year. Results revealed that 4 year-old children's hyperactive, but not aggressive, behavior was associated with an increase in television watching over the ensuing year. These potential child effects, however, were embedded in both proximate and distal ecologies. That is, the association between children's hyperactivity and increases in their television exposure over time was strongest among those in the low-end of the socioeconomic distribution and those whose parents displayed less optimal mental health. It was also stronger among girls. These results underscore the importance of considering child effects in future research and how intra-familial dynamics vary across different types of family contexts. PMID- 26834300 TI - EARLY POSTPARTUM PARENTAL PREOCCUPATION AND POSITIVE PARENTING THOUGHTS: RELATIONSHIP WITH PARENT-INFANT INTERACTION. AB - Parenting behaviors and parent-infant emotional bonding during the early postpartum months play a critical role in infant development. However, the nature and progression of parental thoughts and their relationship with interactive behaviors have received less research. The current study investigated the trajectory of parental thoughts and behaviors among primiparous mothers (n = 18) and fathers (n = 15) and multiparous mothers (n = 13) and fathers (n = 13), which were measured at the first and third postpartum month. At the third postpartum month, the relationship between parental thoughts and parental interactive behaviors also was tested. Mothers and fathers showed high levels of preoccupations and caregiving thoughts during the first postpartum month that significantly declined by the third postpartum month. In contrast, positive thoughts about parenting and the infant increased over the same time interval. Mothers presented higher levels of preoccupations and positive thoughts than did fathers, and first-time parents reported more intense preoccupations than did experienced parents. Although maternal sensitivity was inversely related to maternal anxious thoughts, paternal sensitivity was predicted by higher levels of anxious as well as caregiving and positive thoughts. PMID- 26834302 TI - A Heated Debate: Theoretical Perspectives of Sexual Exploitation and Sex Work. AB - The theoretical and often political framework of sexual exploitation and sex work among women is widely and enthusiastically debated among academic and legal scholars alike. The majority of theoretical literature in this area focuses on the macro perspective, while the micro-level perspective as to theory and causation remains sparse. This article provides a comprehensive overview of the philosophical, legal, and political perspectives pertaining to sexual exploitation of women and girls while addressing the subsequent controversies in the field. PMID- 26834303 TI - Individual Differences in Men's Misperception of Women's Sexual Intent: Application and Extension of the Confluence Model. AB - Men are more likely than women to misperceive a cross-sex companion's degree of sexual interest. The current study extends previous research by using the confluence model (Malamuth et al., 1991) to examine how narcissism and impulsive sensation-seeking are directly and indirectly associated with men's misperception of women's sexual interest. A community sample of young, single men (N = 470) completed audio computer-assisted self-interviews. Using path analyses, hostile masculinity and impersonal sexual orientation were proximal predictors of men's misperception of women's sexual intent. Additionally, narcissism was indirectly related to men's misperception through hostile masculinity. Impulsive sensation seeking was directly and indirectly related to men's misperceptions through impersonal sexual orientation. Although there was a bivariate relationship between alcohol consumption and misperception, this relationship was not significant in the path model. Overall, these findings demonstrate the importance of considering how personality traits increase the risk for misperception. PMID- 26834304 TI - Differential Effectiveness of Head Start in Urban and Rural Communities. AB - Recent research suggests that Head Start may be differentially effective in improving low-income children's early language and literacy skills based on a number of individual- and family-level characteristics. Using data from the Head Start Impact Study (n = 3503; 50% male, 63% treatment group), the present study extends this work to consider program impact variation based on centers' location in urban versus rural communities. Results indicate that Head Start is more effective in increasing children's receptive vocabulary (as measured by the PPVT) in urban areas and their oral comprehension (as measured by the Woodcock-Johnson Oral Comprehension task) in rural areas. Additional analyses suggest that related characteristics of the center - including concentration of dual language learners and provision of transportation services - may underlie these associations. Implications for research on program evaluation and policy are discussed. PMID- 26834305 TI - Child Temperamental Flexibility Moderates the Relation between Positive Parenting and Adolescent Adjustment. AB - Temperamental flexibility and lower positive parenting are associated with internalizing and externalizing problems; however, youth varying in flexibility may be differentially affected by positive parenting in the prediction of symptoms. We examined whether children's flexibility moderated prospective relations between maternal and paternal positive parenting and youth internalizing and externalizing symptoms during adolescence. Participants (N =775, 71% male) and their caregivers completed measures when youth were 10-12 and 12-14 years old. Father positive parenting interacted with child flexibility to predict father-reported internalizing and externalizing problems. Consistent with the diathesis-stress model, children lower in flexibility experienced greater symptoms than children higher in flexibility in lower positive parenting contexts. Among children lower in flexibility, lower paternal positive parenting was associated with greater internalizing and externalizing symptoms compared to higher paternal positive parenting. However, among youth higher in flexibility, symptom levels were similar regardless of whether youth experienced lower or higher paternal positive parenting. PMID- 26834307 TI - Equilibrium studies of cobalt(II) extraction with 2-pyridineketoxime from mixed sulphate/chloride solution. AB - In present paper the equilibrium of cobalt extraction with 1-(2-pyridyl)tridecan 1-one oxime from the chloride/sulphate solutions was studied. The presented results indicated that extraction depends on a number of process variables, including the pH, metal and Cl- concentration in the aqueous feed, and concentration of the oxime in the organic phase. The created cobalt-complexes with the 2-pyridine ketoxime were stable and only concentrated HCl was found to be a suitable stripping agent for coordinated metal. The separation of Co(II) from Zn(II), Ni(II) and Cu(II) was also studied, but the selective recovery of the metals was possible using the multi-stage stripping process. PMID- 26834306 TI - IRMM-1000a and IRMM-1000b uranium reference materials certified for the production date. Part I: methodology, preparation and target characteristics. AB - The paper describes the preparation and production of the reference materials, IRMM-1000a and IRMM-1000b, certified for the production date based on the 230Th/234U radiochronometer in compliance with ISO Guide 34:2009. The production date of the reference materials corresponds to the last separation of 230Th from 234U, i.e. when the initial daughter nuclide content in the material was finally removed. For the preparation low-enriched uranium was used, which was purified using a unique methodology to guarantee high U recovery and Th separation efficiency. The CRM is intended for calibration, quality control, and assessment of method performance in nuclear forensics and safeguards. PMID- 26834308 TI - Adsorption and removal of strontium in aqueous solution by synthetic hydroxyapatite. AB - Hydroxyapatite (HAP) is a main mineral constituent of bone and tooth and has an outstanding biocompatibility. HAP is a possible sorbent for heavy metals in wastewater due to its high adsorption capacity and low water solubility. We developed a removal system of 90Sr from aqueous solution by HAP column procedure. More than 90 % of 90Sr was adsorbed and removed from the 90Sr containing solution. Divalent cations, Ca2+, had little effect on the removal of 90Sr up to a concentration of 1 mmol L-1. This clearly indicates that the HAP column technique is advantageous with respect to the capacity to adsorb 90Sr from water present in the environment. PMID- 26834310 TI - Air sampling filtration media: Collection efficiency for respirable size selective sampling. AB - The collection efficiencies of commonly used membrane air sampling filters in the ultrafine particle size range were investigated. Mixed cellulose ester (MCE; 0.45, 0.8, 1.2, and 5 MUm pore sizes), polycarbonate (0.4, 0.8, 2, and 5 MUm pore sizes), polytetrafluoroethylene (PTFE; 0.45, 1, 2, and 5 MUm pore sizes), polyvinyl chloride (PVC; 0.8 and 5 MUm pore sizes), and silver membrane (0.45, 0.8, 1.2, and 5 MUm pore sizes) filters were exposed to polydisperse sodium chloride (NaCl) particles in the size range of 10-400 nm. Test aerosols were nebulized and introduced into a calm air chamber through a diffusion dryer and aerosol neutralizer. The testing filters (37 mm diameter) were mounted in a conductive polypropylene filter-holder (cassette) within a metal testing tube. The experiments were conducted at flow rates between 1.7 and 11.2 l min-1. The particle size distributions of NaCl challenge aerosol were measured upstream and downstream of the test filters by a scanning mobility particle sizer (SMPS). Three different filters of each type with at least three repetitions for each pore size were tested. In general, the collection efficiency varied with airflow, pore size, and sampling duration. In addition, both collection efficiency and pressure drop increased with decreased pore size and increased sampling flow rate, but they differed among filter types and manufacturer. The present study confirmed that the MCE, PTFE, and PVC filters have a relatively high collection efficiency for challenge particles much smaller than their nominal pore size and are considerably more efficient than polycarbonate and silver membrane filters, especially at larger nominal pore sizes. PMID- 26834309 TI - An examination of an adapter method for measuring the vibration transmitted to the human arms. AB - The objective of this study is to evaluate an adapter method for measuring the vibration on the human arms. Four instrumented adapters with different weights were used to measure the vibration transmitted to the wrist, forearm, and upper arm of each subject. Each adapter was attached at each location on the subjects using an elastic cloth wrap. Two laser vibrometers were also used to measure the transmitted vibration at each location to evaluate the validity of the adapter method. The apparent mass at the palm of the hand along the forearm direction was also measured to enhance the evaluation. This study found that the adapter and laser-measured transmissibility spectra were comparable with some systematic differences. While increasing the adapter mass reduced the resonant frequency at the measurement location, increasing the tightness of the adapter attachment increased the resonant frequency. However, the use of lightweight (<=15 g) adapters under medium attachment tightness did not change the basic trends of the transmissibility spectrum. The resonant features observed in the transmissibility spectra were also correlated with those observed in the apparent mass spectra. Because the local coordinate systems of the adapters may be significantly misaligned relative to the global coordinates of the vibration test systems, large errors were observed for the adapter-measured transmissibility in some individual orthogonal directions. This study, however, also demonstrated that the misalignment issue can be resolved by either using the total vibration transmissibility or by measuring the misalignment angles to correct the errors. Therefore, the adapter method is acceptable for understanding the basic characteristics of the vibration transmission in the human arms, and the adapter measured data are acceptable for approximately modeling the system. PMID- 26834311 TI - Spatio-Temporal Dimensions of Child Poverty in America, 1990-2010. AB - The persistence of childhood poverty in the United States, a wealthy and developed country, continues to pose both an analytical dilemma and public policy challenge, despite many decades of research and remedial policy implementation. In this paper, our goals are twofold, though our primary focus is methodological. We attempt both to examine the relationship between space, time, and previously established factors correlated with childhood poverty at the county level in the continental United States as well as to provide an empirical case study to demonstrate an underutilized methodological approach. We analyze a spatially consistent dataset built from the 1990 and 2000 U.S. Censuses, and the 2006-2010 American Community Survey. Our analytic approach includes cross-sectional spatial models to estimate the reproduction of poverty for each of the reference years as well as a fixed effects panel data model, to analyze change in child poverty over time. In addition, we estimate a full space-time interaction model, which adjusts for spatial and temporal variation in these data. These models reinforce our understanding of the strong regional persistence of childhood poverty in the U.S. over time and suggest that the factors impacting childhood poverty remain much the same today as they have in past decades. PMID- 26834312 TI - 2-Butoxyethanol and Benzyl Alcohol Reactions with the Nitrate Radical: Rate Coefficients and Gas-Phase Products. AB - The bimolecular rate coefficients [Formula: see text] and [Formula: see text] were measured using the relative rate technique at (297 +/- 3) K and 1 atmosphere total pressure. Values of (2.7 +/- 0.7) and (4.0 +/- 1.0) * 10-15 cm3 molecule-1 s-1 were observed for [Formula: see text] and [Formula: see text], respectively. In addition, the products of [Formula: see text] and [Formula: see text] gas phase reactions were investigated. Derivatizing agents O-(2,3,4,5,6 pentafluorobenzyl)hydroxylamine and N, O-bis (trimethylsilyl)trifluoroacetamide and gas chromatography mass spectrometry (GC/MS) were used to identify the reaction products. For [Formula: see text] reaction: hydroxyacetaldehyde, 3 hydroxypropanal, 4-hydroxybutanal, butoxyacetaldehyde, and 4-(2-oxoethoxy)butan-2 yl nitrate were the derivatized products observed. For the [Formula: see text] reaction: benzaldehyde ((C6H5)C(=O)H) was the only derivatized product observed. Negative chemical ionization was used to identify the following nitrate products: [(2-butoxyethoxy)(oxido)amino]oxidanide and benzyl nitrate, for [Formula: see text] and [Formula: see text], respectively. The elucidation of these products was facilitated by mass spectrometry of the derivatized reaction products coupled with a plausible 2-butoxyethanol or [Formula: see text] reaction mechanisms based on previously published [Formula: see text] gas-phase mechanisms. PMID- 26834313 TI - Modeling Women's Menstrual Cycles using PICI Gates in Bayesian Network. AB - A major difficulty in building Bayesian network (BN) models is the size of conditional probability tables, which grow exponentially in the number of parents. One way of dealing with this problem is through parametric conditional probability distributions that usually require only a number of parameters that is linear in the number of parents. In this paper, we introduce a new class of parametric models, the Probabilistic Independence of Causal Influences (PICI) models, that aim at lowering the number of parameters required to specify local probability distributions, but are still capable of efficiently modeling a variety of interactions. A subset of PICI models is decomposable and this leads to significantly faster inference as compared to models that cannot be decomposed. We present an application of the proposed method to learning dynamic BNs for modeling a woman's menstrual cycle. We show that PICI models are especially useful for parameter learning from small data sets and lead to higher parameter accuracy than when learning CPTs. PMID- 26834315 TI - Stimuli-responsive supramolecular hydrogels with high extensibility and fast self healing via precoordinated mussel-inspired chemistry. AB - Supramolecular hydrogels have the advantages of stimuli responsiveness and self healing compared to covalently crosslinked hydrogels. However, the existing supramolecular hydrogels are usually poor in mechanical properties especially in extensibility. In addition, these supramolecular hydrogels need a long self healing time and have low self-healing efficiency. In this manuscript, we report a novel strategy to develop highly extensible and fast self-healing supramolecular hydrogels by using pre-coordinated mussel-inspired catechol-Fe3+ complexes as dynamic crosslinkers. The hydrogel can be fabricated and cast into various shapes by one-step photo-crosslinking. Thus fabricated hydrogels can be stretched beyond 10 times their original lengths, and the high extensibility can completely recover within a very short time (less than 20 minutes) even after the hydrogels are entirely cut apart. Utilizing the dynamic nature of supramolecular hydrogels, we can realize different mechanical behaviors including strength, extensibility and recoverability by varying the loading conditions. In addition, the hydrogels respond to multiple stimuli including mechanical force, temperature and certain chemicals because of the dynamic catechol-Fe3+ bond. PMID- 26834314 TI - Navigating the interface between learning and cognition. AB - The interface of learning and cognition applied to the study of animal behavior represents a target for significant progress if conceptual barriers can be reduced. Is animal behavior exclusively a product of learning or cognition, or are both implicated? Are special (i.e., new) methods required to study cognition or will the enterprise be accomplished by using well-established methods from learning? What types of hypotheses need to be tested to dissociate cognition from learning, and may these hypotheses be profitably tested? This article addresses the above questions by focusing on conceptual, methodological, and hypothesis testing perspectives for navigating the interface between learning and cognition. Examples from contemporary research are used to develop some suggestions for best practices. The development of a rodent model of episodic memory is used as a case study to feature the validation of an animal model of cognition. PMID- 26834316 TI - Effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. AB - [Purpose] This study examined the effects of neuromuscular training on knee joint stability after anterior cruciate ligament reconstruction. [Subjects and Methods] The subjects were 16 adults who underwent arthroscopic anterior cruciate reconstruction and neuromuscular training. The Lysholm scale was used to assess functional disorders on the affected knee joint. A KT-2000 arthrometer was used to measure anterior displacement of the tibia against the femur. Surface electromyography was used to detect the muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus before and after neuromuscular training. [Results] There was significant relaxation in tibial anterior displacement of the affected and sound sides in the supine position before neuromuscular training. Furthermore, the difference in the tibial anterior displacement of the affected knee joints in the standing position was reduced after neuromuscular training. Moreover, the variation of the muscle activation evoked higher muscle activation of the vastus medialis oblique, vastus lateralis, biceps femoris, and semitendinosus. [Conclusion] Neuromuscular training may improve functional joint stability in patients with orthopedic musculoskeletal injuries in the postoperative period. PMID- 26834317 TI - Effects of shoulder stabilization exercise on pain and function in patients with neck pain. AB - [Purpose] The objective of this study was to investigate the effects of shoulder stability exercise on pain and function in neck pain patients. [Subjects] The study design consisted of a shoulder stability exercise group and a control group. [Methods] The effects of the therapies were evaluated using a visual analog scale of pain, a pressure pain threshold, neck disability index, cervical range of motion, and a closed kinetic chain test. Each group received treatment five times per week for 4 weeks. [Results] Pain levels showed no significant differences between groups, while pain threshold in all muscles, showed significant increases for both control groups. Neck disability significantly decreased for both groups and the differences between the groups were statistically significant. Ranges of motion and limb stability were measured before and after the exercise period. Flexion, extension, and right rotation were not significantly different between groups. The results showed no significant differences in shoulder stability between the groups. [Conclusion] The use of this exercise should have pronounced effects on pain reduction and functional improvement and should also improve the quality of life in patients with neck pain. PMID- 26834318 TI - A randomized controlled trial of the computer-based cognitive rehabilitation program for children (CoTras-C) to examine cognitive function and visual perception in children with developmental disabilities. AB - [Purpose] This study aimed to investigate the effects of a computer-based cognitive rehabilitation program for children with developmental disabilities. [Subjects] Subjects included 29 children with developmental disabilities. [Methods] The subjects were randomly allocated to either the experimental group or control group. Experimental group subjects received computer-based cognitive rehabilitation using the CoTras-C while control group subjects received conventional cognitive rehabilitation. All subjects received 20 sessions (2 days a week for 10 weeks) of the experimental or control intervention for 30 minutes. To compare the two groups, the Korean-Developmental Test of Visual Perception-2 and Kaufman Assessment Battery for Children were performed before and after the intervention. [Results] Both groups showed statistically significant improvement in their scores after intervention. Additionally, there were significant differences in the scores between the two groups. [Conclusion] The computer-based cognitive rehabilitation with CoTras-C may be helpful in improving the recovery of cognitive function and visual perception in children with developmental disabilities. PMID- 26834319 TI - Work-related musculoskeletal disorders among occupational therapists in Korea. AB - [Purpose] The purpose of the study was to identify general characteristics of occupational therapists in Korea and to investigate the present conditions of their work-related musculoskeletal disorders (WRMD) in order to present preliminary data for its prevention and directions for improvement. [Subjects and Methods] This study was conducted by performing a survey about WRMD among 95 occupational therapists working in Korea. Frequency analysis was conducted for the work-related general characteristics of subjects and for parts of the body with musculoskeletal disorder, and a chi(2) test was used to analyze the association between the presence of WRMD characteristics and each general characteristic. [Results] The parts of the body involved the most were the shoulders, hands, and neck (in decreasing order), and the work-related general characteristics shown to be associated with WRMD were the gender and the mean length of employment period. [Conclusion] The results of this study revealed that occupational therapists in Korea were extremely vulnerable to WRMD, and that realistic measures should be prepared swiftly for its prevention and treatment. PMID- 26834320 TI - Effect of tongue strength training using the Iowa Oral Performance Instrument in stroke patients with dysphagia. AB - [Purpose] The aim of this study was to evaluate the effectiveness of a structured program of resistance training for the tongue in order to improve swallowing function in stroke patients with dysphagia. [Subjects and Methods] Twenty-seven stroke patients with dysphagia were randomly divided into two groups. The experimental group participated in a resistance-training program involving a 1 repetition maximum, with an intensity of 80%, along with 50 repetitions per day each for the anterior and posterior regions of the tongue. Both groups received conventional therapy for dysphagia for 30 min per day, 5 times per week, for 6 weeks. [Results] The experimental group showed statistically significant improvements in both, the anterior and posterior regions of the tongue. In contrast, the control group showed significant improvements only in the anterior region of the tongue. In the videofluoroscopic dysphagia scale evaluation, improvement was noted at both, the oral and pharyngeal stages in the experimental group, whereas significant improvements were only noted in the oral stage and total score in the control group. [Conclusion] Our study confirmed that tongue resistance training is an effective intervention for stroke patients with dysphagia, offering improved tongue muscle strength and overall improvement in swallowing. PMID- 26834321 TI - Quantitative postural analysis and pain in children and adolescents victims of burns. AB - [Purpose] This study aimed to quantitatively assess postural alignment in both frontal and sagittal planes, as well as pain in children and adolescents victims of burn injuries. [Subjects and Methods] This cross-sectional study included 21 victims of burns, nine children (age [mean +/- SD], 7.3 +/- 1.1 yrs) and 12 adolescents (12,0 +/- 1.4 yrs), classified as medium and large burns, being investigated on pain and postural alignment evaluated by photogrammetry. Pain intensity was assessed by face scales and postural examination included the assessment of global and thoraco-lumbo-pelvic alignment by previously designed protocols. [Results] Only two adolescents reported mild pain associated with burn injuries, whereas deviations of the projection of the gravity center; forward head posture, and scapular asymmetry were observed in both groups. In the analysis of the thoraco-lumbo-pelvic alignment, children tended to have anterior inclination trunk, increased thoracic kyphosis and lumbar lordosis, while in adolescents, increased thoracic kyphosis and lumbar lordosis were observed. [Conclusion] The results indicate that due to the postural alterations and asymmetries in both frontal and sagittal planes, there is an increased risk of developing scoliosis and possible future pain. Thus, physiotherapy is indicated and should be maintained until complete growth is reached. PMID- 26834322 TI - Comparison of knowledge of and attitudes toward dementia between health-related and non-health-related university students. AB - [Purpose] This study compared the knowledge of and attitudes toward dementia between health-related and non-health-related students. [Subjects] The subjects consisted of a total of 416 people, 213 health-related students and 203 non health-related students, at K University, which is located in Gyeongsangbuk-do, Republic of Korea, between May 1 and 14, 2014. [Methods] The subjects answered a self-administered questionnaire about their knowledge of and attitudes toward dementia. [Results] There was a significant difference in knowledge of and attitudes toward dementia between the two groups examined. [Conclusion] Health related students displayed higher knowledge of dementia and a more positive attitude toward dementia compared with non-health-related students. In the future, education to cultivate professional knowledge about dementia and enhance positive attitudes toward dementia should be provided continuously to health related students. This is because students in health-related fields will likely provide services to patients with dementia in the clinical field. Additionally, as they will likely provide support to the elderly in the future, non-health related students also need to be educated about and develop positive attitudes toward dementia. PMID- 26834323 TI - Correlation between the selective control assessment of lower extremity and pediatric balance scale scores in children with spastic cerebral palsy. AB - [Purpose] The purpose of this study was to investigate the correlation between the Selective Control Assessment of Lower Extremity (SCALE) and Pediatric Balance Scales (PBS) in children with spastic cerebral palsy and further to test whether the SCALE is a valid tool to predict the PBS. [Subjects and Methods] A cross sectional study was conducted to evaluate the SCALE and PBS in 23 children (9 females, 14 males, GMFCS level I-III) with spastic cerebral palsy. [Results] Both the SCALE and PBS scores for children with spastic hemiplegia were significantly higher than those for children with spastic diplegia. The scores for SCALE items were low for distal parts. The PBS items that were difficult for the participants to perform were items 8, 9, 10, and 14 with the highest difficulty experienced for item 8 followed by items 9, 10, and 14. The correlation coefficient (0.797) between the SCALE and PBS scores was statistically significant. The correlations between each SCALE item and the PBS scores were also statistically significant. SCALE items were significantly correlated with two PBS dimensions (standing and postural change). [Conclusion] In SCALE assessment, more severe deficits were observed in the distal parts. Standing and postural changes in the PBS method were difficult for the participants to perform. The two tests, that is, the SCALE and PBS, were highly correlated. Therefore, the SCALE is useful to prediction of PBS outcomes and is also applicable as a prognostic indicator for treatment planning. PMID- 26834324 TI - Analysis of the risk factors of musculoskeletal disease among dentists induced by work posture. AB - [Purpose] The purpose of this study was to ergonomically evaluate the work posture of dentists to examine their subsequent risk of developing musculoskeletal diseases. [Subjects and Methods] Scenes in which the three dentists performed procedures at their dental clinics were videotaped. The videotapes of the dentists' work postures were evaluated and analyzed by using the Rapid Upper Limb Assessment (RULA) and Quick Exposure Check (QEC). [Results] The RULA analysis of the dentists' work posture indicated, "improvement required" in the posture used to treat the anterior and "instant improvement required" in the posture used to treat the maxillary second molar. Of all the work postures studied, the risk was considered particularly high in the lower back and neck, implying prominent problems in these body parts. The QEC analysis showed that the worst work posture was that required to treat the maxillary second molar, which led to a high risk of neck problems and vibrations. [Conclusion] The neck area has the highest risk of developing musculoskeletal disease. Hence, regular rests and the provision of information regarding muscle strengthening exercise for the neck are necessary. PMID- 26834325 TI - Comparison of physical function according to the lumbar movement method of stabilizing a patient with chronic low back pain. AB - [Purpose] The purpose of this study was to examine the changes caused by lumbar stabilization exercises in chronic low back pain patients. [Subjects and Methods] Swiss ball exercise regimen group and sling exercise regimen group exercised for 30 minutes a day, 5 days a week, for 12 weeks. The control group was to continue performing their usual daily living activities. [Results] We obtained significant results in both the Swiss ball and sling exercise groups, but not in the control group. The best effect was obtained in the sling exercise group. [Conclusion] The Oswestry Low Back Pain Disability Index and visual pain scale scores of the patients with low back pain decreased in both the Swiss ball exercise group and the sling exercise group, and these patients experienced an increase in waist isometric muscular strength after 12 weeks of exercise compared with those doing no exercise (the control group). PMID- 26834326 TI - The effects of extracorporeal shock wave therapy on frozen shoulder patients' pain and functions. AB - [Purpose] The present study was conducted to examine the effects of extracorporeal shock wave therapy on frozen shoulder patients' pain and functions. [Subjects] In the present study, 30 frozen shoulder patients were divided into two groups: an extracorporeal shock wave therapy group of 15 patients and a conservative physical therapy group of 15 patients. [Methods] Two times per week for six weeks, the extracorporeal shock wave therapy group underwent extracorporeal shock wave therapy, and the conservative physical therapy group underwent general physical therapy. Visual analog scales were used to measure frozen shoulder patients' pain, and patient-specific functional scales were used to evaluate the degree of functional disorders. [Results] In intra group comparisons, the two groups showed significant decreases in terms of visual analog scales and patient-specific functional scales, although the extracorporeal shock wave therapy group showed significantly lower scores than the conservative physical therapy group. [Conclusion] Extracorporeal shock wave therapy is considered an effective intervention for improving frozen shoulder patients' pain and functions. PMID- 26834327 TI - Usefulness of a 50-meter round walking test for fall prediction in the elderly requiring long-term care. AB - [Purpose] This study aimed to verify the usefulness of a 50-m round walking test developed as an assessment method for walking ability in the elderly. [Subjects] The subjects were 166 elderly requiring long-term care individuals (mean age, 80.5 years). [Methods] In order to evaluate the factors that had affected falls in the subjects in the previous year, we performed the 50-m round walking test, functional reach test, one-leg standing test, and 5-m walking test and measured grip strength and quadriceps strength. [Results] The 50-m round walking test was selected as a variable indicating fall risk based on the results of multiple logistic regression analysis. The cutoff value of the 50-m round walking test for determining fall risk was 0.66 m/sec. The area under the receiver operating characteristic curve was 0.64. The sensitivity of the cutoff value was 65.7%, the specificity was 63.6%, the positive predictive value was 55.0%, the negative predictive value was 73.3%, and the accuracy was 64.5%. [Conclusion] These results suggest that the 50-m round walking test is a potentially useful parameter for the determination of fall risk in the elderly requiring long-term care. PMID- 26834328 TI - Comparison of therapeutic duration of therapeutic ultrasound in patients with knee osteoarthritis. AB - [Purpose] The aim of study was to compare different durations of ultrasound in patients with knee osteoarthritis. [Subjects and Methods] One hundred patients diagnosed with bilateral knee osteoarthritis (OA) were enrolled in this study. Patients were divided into two groups. The first group (G1) received 4 minutes of ultrasound. The second group (G2) received the exact same treatment, but the duration of ultrasound was longer at 8 minutes. Patients in both groups underwent a total of 10 ultrasound over 2 weeks. Following treatment, all patients provided self-evaluations of pain via the Visual Analog Scale (VAS), overall physical function with WOMAC, disability via the Lequesne index (Leq), and depressive symptoms with the Beck Depression Index (BDI). [Results] There were no significant differences in VAS, WOMAC Leq, and BDI values between groups 1 and 2. After treatment, VAS, WOMAC, Leq, and BDI values improved for both treatment groups. However, following treatment, G2 had significantly greater values for WOMAC functional and total scores than G1. No statistically significant differences were observed for VAS scores while inactive, WOMAC pain and stiffness scores, and BDI values after treatment between both groups. VAS pain scores while active and Leq index values were significantly lower in G1 than G2. [Conclusion] Patients in both groups demonstrated improved functionality, pain and psychological status following a consistent, 2-week regimen of 4-minute or 8 minute treatments with ultrasound. Yet, patients that experienced longer treatment durations of 8 minutes demonstrated better outcomes in pain and the ability to carry out activities of daily living. PMID- 26834329 TI - Characteristics and rehabilitation for patients with spinal cord stab injury. AB - [Purpose] The objective of the study was to compare the incidence, diagnosis, treatment, and prognosis of patients with spinal cord stab injury to those with the more common spinal cord contusion injury. [Subjects] Of patients hospitalized in China Rehabilitation Research Center from 1994 to 2014, 40 of those having a spinal cord stab injury and 50 with spinal cord contusion were selected. [Methods] The data of all patients were analyzed retrospectively. The cases were evaluated by collecting admission and discharge ASIA (American Spinal Injury Association) and ADL (activity of daily living) scores. [Results] After a comprehensive rehabilitation program, ASIA and ADL scores of patients having both spinal cord stab injury and spinal cord contusion significantly increase. However, the increases were noted to be higher in patients having a spinal cord stab injury than those having spinal cord contusion. [Conclusion] Comprehensive rehabilitation is effective both for patients having spinal cord stab injury and those with spinal cord contusion injury. However, the prognosis of patients having spinal cord stab injury is better than that of patients with spinal cord contusion. PMID- 26834330 TI - Gait speed and related factors in Parkinson's disease. AB - [Purpose] The aim of this study was to investigate the relationship between gait speed and various factors in ambulatory patients with idiopathic Parkinson's disease. [Subjects] Fifty ambulatory patients with idiopathic Parkinson's disease who were admitted to an outpatient clinic were included in this cross-sectional study. [Methods] The Hoehn and Yahr Scale was used for measurement of the disease severity. Gait speed was measured by the 10-Meter Walk Test. Mobility status was assessed by Timed Up and Go Test. The Hospital Anxiety and Depression Scale was used for evaluation of emotional state. Cognitive status was examined with the Mini-Mental State Examination. The Downton Index was used for fall risk assessment. Balance was evaluated with the Berg Balance Scale. Comorbidity was measured with the Cumulative Illness Rating Scale. The 36-Item Short Form Health Survey was completed for measurement of quality of life. [Results] The mean age was 66.7 (47-83) years. Twenty-eight (56%) patients were men. Gait speed was correlated positively with height, male gender, Mini-Mental Examination score, Berg Balance Scale score and physical summary scores of the 36-Item Short Form Health Survey. On the other hand, there was a negative correlation between gait speed and age, disease severity, TUG time, Downton Index, fear of falling, previous falls and the anxiety and depression scores of the Hospital Anxiety and Depression Scale. There was no correlation between gait speed and comorbidity. [Conclusion] The factors related with the slower gait speed are, elder age, clinically advanced disease, poor mobility, fear of falling, falling history, higher falling risk, and mood disorder. PMID- 26834331 TI - Influence of detraining on temporal changes in arterial stiffness in endurance athletes: a prospective study. AB - [Purpose] We examined the effects of detraining on temporal changes in arterial stiffness in endurance athletes. [Subjects] Eighteen female university athletes requiring high endurance exercise capabilities were classified into 2 groups: 10 retired players (detraining group) and 8 active players (training group). [Methods] Brachial-ankle pulse wave velocity, an index of arterial stiffness, was measured a total of 6 times: immediately before retirement of the detraining group and at 1, 2, 3, 6, and 12 months after retirement. [Results] Brachial-ankle pulse wave velocity was measured in the training group at the same 6 points to allow comparison with the detraining group. The brachial-ankle pulse wave velocity in the detraining group increased significantly at 3 and 12 months as compared with that at 0 months and showed a significant increase at 12 months compared with that at 1 month. Moreover, the brachial-ankle pulse wave velocity in the detraining group was significantly higher at 3, 6, and 12 months than in the training group. [Conclusion] These results revealed that detraining may result in increased arterial stiffness from 3 months onward in endurance athletes. PMID- 26834332 TI - Age-associated changes in the level of physical activity in elderly adults. AB - [Purpose] This study aimed to clarify how light-, moderate-, and vigorous intensity physical activity in older adults changes with age, subdividing physical activity according to intensity levels, by using an accelerometer. [Subjects] Older adults living independently in the community were included (n = 106, age: 65-85 years). [Methods] A triaxial accelerometer was used to measure the amount of light-, moderate-, and vigorous-intensity physical activity (1-2.9, 3-5.9, and >=6 metabolic equivalents, respectively) and inactive time over 7 days. Light- and moderate-intensity physical activity levels were further subdivided into 1-1.9, 2-2.9, 3-3.9, and 4-5.9 metabolic equivalents, respectively. [Results] The amount of moderate-intensity physical activity at both sub-levels showed significant inverse correlations with age (r = -0.34, 0.33, respectively), but this was not seen with other levels. Both levels of moderate-intensity physical activity were independently predicted by age using multiple regression analysis adjusted for gender and body mass index. [Conclusion] These results suggest that understanding the reduction in moderate intensity physical activity with age in older adults, subdivided according to intensity level, could be a useful index to increase the amount of higher intensity physical activity in stages, considering individual health conditions. PMID- 26834333 TI - The relationships between lifestyle factors and hypertension in community dwelling Korean adults. AB - [Purpose] This study was performed to determine whether certain lifestyle factors are associated with hypertension in community-dwelling Korean adults. [Subjects and Methods] The subjects were 586 males and 1,135 females > 20 years old who had visited a public health promotion center in Seoul, Republic of Korea to take a survey related to lifestyle factors. Hypertension status was defined according to the criteria of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure VII report. [Results] The relationships between lifestyle factors and hypertension status were assessed using multivariate logistic regression analysis after adjusting for age and gender. Only mental stress and economic status significantly predicted hypertension status. [Conclusion] We conclude that sleep duration, education level, frequency of drinking and smoking status were not associated with hypertension status. However, economic status and mental stress were significantly associated with hypertension in community-dwelling Korean adults, regardless of age or gender. PMID- 26834334 TI - Virtual dual-task treadmill training using video recording for gait of chronic stroke survivors: a randomized controlled trial. AB - [Purpose] The aim of this study was to examine the effects of virtual dual-task treadmill training using a real-world video recording of the gait of individuals with chronic stroke. [Subjects] Forty chronic stroke survivors were randomly divided into two groups of 20 subjects each. [Methods] The experimental group performed virtual dual-task treadmill training using a video recording for 30 minutes per session, three times a week for 4 weeks, whereas the control group performed only treadmill training for 30 minutes per session, three times a week for 4 weeks. A video recording was performed in a large supermarket, and the subjects could walk at their favorable speed on a treadmill. The temporospatial gait variables were measured to examine the training effect. [Results] The experimental and control groups showed statistically significant improvements in the gait variables after training. The enhancement of gait ability was statistically better in the experimental group than in the control group. [Conclusion] Our findings suggest that virtual dual-task treadmill training using a video recording can improve the gait parameters of chronic stroke survivors. PMID- 26834335 TI - Effect of coordination movement using the PNF pattern underwater on the balance and gait of stroke patients. AB - [Purpose] To investigate the effect of coordination movement using the Proprioceptive Neuromuscular Facilitation pattern underwater on the balance and gait of stroke patients. [Subjects and Methods] Twenty stroke patients were randomly assigned to an experimental group that performed coordination movement using the Proprioceptive Neuromuscular Facilitation pattern underwater and a control group (n =10 each). Both the groups underwent neurodevelopmental treatment, and the experimental group performed coordination movement using the Proprioceptive neuromuscular facilitation pattern underwater. Balance was measured using the Berg Balance Scale and Functional Reach Test, and gait was measured using the 10-Meter Walk Test and Timed Up and Go Test. To compare in group data before and after the intervention, paired t-test was used. Independent t-test was used to compare differences in the results of the Berg Balance Scale, Functional Reach Test, 10-Meter Walk Test, and Timed Up and Go Test before and after the intervention between the groups. [Results] Comparison within the groups showed significant differences in the results of the Berg Balance Scale, Functional Reach Test, 10-Meter Walk Test, and Timed Up and Go Test before and after the experimental intervention. On comparison between the groups, there were greater improvements in the scores of the Berg Balance Scale, Functional Reach Test, 10-Meter Walk Test, and Timed Up and Go Test in the experimental group. [Conclusion] The findings demonstrate that coordination movement using the Proprioceptive Neuromuscular Facilitation pattern under water has a significant effect on the balance and gait of stroke patients. PMID- 26834336 TI - Pregnancy physical activity questionnaire (PPAQ): reliability and validity of Turkish version. AB - [Purpose] The aim of this study was to translate the Pregnancy Physical Activity Questionnaire into Turkish and test its reliability and validity among Turkish pregnant women. [Subjects and Methods] The subjects were 204 healthy, single pregnant women between the ages 18 and 40 who volunteered to participate in this study. Reliability was evaluated by measuring the one-week test-retest reliability with the intraclass correlation coefficient and Pearson's correlation analysis. Concurrent validity was examined by comparing the Pregnancy Physical Activity Questionnaire with the long form of the International Physical Activity Questionnaire and step counts with pedometer. [Results] The mean age of the participants was 28.23+/-4.94 years, and the mean for BMI was 26.09+/-4.40. For test-retest reliability, r values were respectively 0.961, 0.934, 0.957 and 0.981 for self-reported sedentary, light, moderate, and vigorous activity, respectively. Intraclass correlation coefficient scores ranged from 0.924 to 0.993. For validity, the Pearson's correlation coefficients between the Pregnancy Physical Activity Questionnaire and long form of the International Physical Activity Questionnaire ranged from moderate (r = 0.329) to high (r = 0.672). The correlation value between the total score of the Pregnancy Physical Activity Questionnaire and the step counts was 0.70. [Conclusion] The Turkish version of the Pregnancy Physical Activity Questionnaire is a valid and reliable tool for measurement of the physical activity level of pregnant women. PMID- 26834337 TI - An effective strategy to reduce blood pressure after forest walking in middle aged and aged people. AB - [Purpose] Forest walking may be effective for human health, but little information is available about effects of energy expenditure on blood pressure responses after forest walking. The aim of this study was to investigate the relationship between the activity energy expenditure and changes in blood pressure in individuals after forest walking. [Subjects] The subjects were 54 middle-aged and elderly people. [Methods] All subjects walked in the forest for approximately 90 min. Blood pressure, salivary amylase, and the Profile of Mood States were evaluated before and after forest walking, and activity energy expenditure was monitored throughout forest walking. Subjects were divided into two groups according to mean arterial pressure changes: a responder group (>5% decreases) and a nonresponder group (<5%). [Results] Forest walking significantly reduced the mean arterial pressure and improved the Profile of Mood States in both groups. Activity energy expenditure was related to changes in mean arterial pressure in the responder group, while this relation was not observed in the nonresponder group. Differential activity energy expenditure did not strongly affect improvement of the Profile of Mood States. [Conclusion] Greater walking related greater activity energy expenditure might be required to accentuate physiological beneficial effects on in middle-aged and aged people. Furthermore, the forest environment per se can attenuate psychological stress. PMID- 26834338 TI - The reliability, validity and correlation of two observational gait scales assessed by video tape for Chinese subjects with hemiplegia. AB - To test the reliability of the Wisconsin Gait Scale (WGS) and the Gait Abnormality Rating Scale (GARS) for hemiplegic Chinese subjects, as well as to establish the concurrent validity of these two scales with clinical measurements. [Subjects] Twenty hemiplegic stroke subjects were recruited for this study. [Methods] The subjects walked along a 10-meter walkway and their gait was videotaped from 4 directions. Two physical therapists assessed the subjects' gait using the aforementioned scales by watching the video tape. The Intraclass Correlation Coefficient (ICC) was calculated for the two physiotherapists' scores for each category and the total scores to assess the reliability. Concurrent validity was tested by comparing the total scores to subjects' walking speed, the Fugl-Meyer assessment, the Motricity Index of the lower limb, and the Composite Spasticity Index of the lower limb. [Results] The ICC of WGS was 0.961 for intra rater reliability, and 0.945 for inter-rater reliability. The ICC of GARS was 0.708 for intra-rater reliability and 0.875 for inter-rater reliability. The correlations of the two scales with walking speed, the Fugl-Meyer assessment and the Motricity Index were statistically significant. [Conclusion] Both the Wisconsin Gait Scale and the Gait Abnormality Rating Scale are reliable and valid protocols for measuring the hemiplegic gait of stroke patients. PMID- 26834339 TI - Maximum inspiratory pressure and rapid shallow breathing index as predictors of successful ventilator weaning. AB - [Purpose] To investigate the predictive value of maximum inspiratory pressure (MIP) and the rapid shallow breathing index (RSBI) in a ventilator weaning protocol and to evaluate the differences between clinical and surgical patients in the intensive care unit. [Subjects and Methods] Patients aged >=15 years who underwent orotracheal intubation for mechanical ventilation and who met the criteria of the weaning protocol were included in the study. Receiver operating characteristic (ROC) curves were calculated for the analysis of each index. [Results] Logistic regression analysis was also performed. MIP showed greater sensitivity and specificity [area under the curve (AUC): 0.95 vs. 0.89] and likelihood ratios (LR) (positive(+): 20.85 vs. 9.45; negative(-): 0.07 vs. 0.17) than RSBI in the overall sample (OS) as well as in clinical patients (CP) (AUC: 0.99 vs. 0.90; LR+: 24.66 vs. 7.22; LR-: 0.01 vs. 0.15) and surgical patients (SP) (AUC: 0.99 vs. 0.87; LR+: 9.33 vs. 5.86; LR-: 0.07 vs. 0.14). The logistic regression analysis revealed that both parameters were significantly associated with the weaning success. The MIP showed greater accuracy than the RSBI (OS: 0.93 vs. 0.85; CP: 0.98 vs. 0.87; SP: 0.93 vs. 0.87). [Conclusion] Both parameters are good predictors of successful ventilator weaning. PMID- 26834340 TI - Association between occlusal force and physical functions in preschool children: a comparison of males and females. AB - [Purpose] To determine and compare changes over time in the physical strength of male and female children aged 4-5 years by measuring physical functions such as occlusal forces. [Subjects and Methods] The occlusal force, weight, height, grip strength, standing long jump, ball throwing, timed up and go (TUG), and the 25-m run time were measured of 331 children to determine their physical strength. All the children understood and were capable of completing all tests. [Results] Occlusal force among male infants significantly correlated with all items except ball throwing. Stepwise multiple regression analysis independently associated occlusal force with grip strength. In contrast, occlusal force of female infants significantly correlated with all the tested items. Stepwise multiple regression analysis also independently associated occlusal force with grip strength and TUG in females. [Conclusion] Grip strength indicating upper-limb muscle strength correlated with occlusal forces in both male and female children, whereas TUG, balance and walking ability indicating muscle strength of the lower limbs, correlated with items relevant to everyday functions in female infants. These findings show that different factors are involved in the occlusal forces of male and female children. PMID- 26834341 TI - Does Nordic walking improves the postural control and gait parameters of women between the age 65 and 74: a randomized trial. AB - [Purpose] To assess the effect of 12-weeks Nordic walking training on gait parameters and some elements of postural control. [Subjects and Methods] Sixty seven women aged 65 to 74 years were enrolled in this study. The subjects were divided into a Nordic Walking group (12 weeks of Nordic walking training, 3 times a week for 75 minutes) and a control group. In both study groups, a set of functional tests were conducted at the beginning and at the end of the study: the Forward Reach Test (FRT) and the Upward Reach Test (URT) on a stabilometric platform, and the analysis of gait parameters on a treadmill. [Results] The NW group showed improvements in: the range of reach in the FRT test and the URT test in compared to the control group. The length of the gait cycle and gait cycle frequency also showed changes in the NW group compared to the control group. [Conclusion] A 12-week NW training program had a positive impact on selected gait parameters and may improve the postural control of women aged over 65 according to the results selected functional tests. PMID- 26834342 TI - Predictors of energy cost during stair ascent and descent in individuals with chronic stroke. AB - [Purpose] This study aimed to determine which clinical measures of walking performance and lower limb muscle strength would predict energy cost during stair ascent and descent in community-dwelling individuals with stroke. [Subjects and Methods] Regression analysis of cross-sectional data from 55 individuals between one and five years post-stroke was used to investigate the measures of walking (speed and distance covered during the 6-minute walk test [6MWT]), and strength of the paretic knee extensor and ankle plantar flexor muscles would predict energy cost during stair ascent and descent. [Results] Three predictors (habitual walking speed, distance covered during the 6MWT, and strength of the paretic knee extensor muscles) were kept in the model. Habitual walking speed alone explained 47% of the variance in energy cost during stair ascent and descent. When the strength of the paretic knee extensor muscles was included in the model, the explained variance increased to 53%. By adding the distance covered during the 6MWT, the variance increased to 58%. [Conclusion] Habitual walking speed, distance covered during the 6MWT, and strength of the paretic knee extensor muscles were significant predictors of energy cost during stair ascent and descent in individuals with mild walking limitations. PMID- 26834343 TI - The influence of revised high-heeled shoes on foot pressure and center of pressure during standing in young women. AB - [Purpose] Revised high-heeled shoes were developed to minimize foot deformities by reducing excessive load on the forefoot during walking or standing in adult females, who frequently wear standard high-heeled shoes. Specifically, this study aimed to investigate the effects of revised high-heeled shoes on foot pressure distribution and center of pressure distance during standing in adult females. [Subjects and Methods] Twelve healthy adult females were recruited to participate in this study. Foot pressures were obtained under 3 conditions: barefoot, in revised high-heeled shoes, and in standard 7-cm high-heeled shoes. Foot pressure was measured using the Tekscan HR mat scan system. One-way repeated analysis of variance was used to compare the foot pressure distribution and center of pressure distance under these 3 conditions. [Results] The center of pressure distance between the two lower limbs and the fore-rear distribution of foot pressure were significantly different for the 3 conditions. [Conclusion] Our findings support the premise that wearing revised high-heeled shoes seems to provide enhanced physiologic standing posture compared to wearing standard high heeled shoes. PMID- 26834344 TI - What is the role of Semmes-Weinstein monofilament testing in the diagnosis of electrophysiologically graded carpal tunnel syndrome? AB - [Purpose] The aim of the study was to investigate the ability of Semmes-Weinstein Monofilament testing to detect carpal tunnel syndrome, as well as moderate-to severe carpal tunnel syndrome using varying thresholds and methods. [Subjects] Clinical and electrophysiological data of 62 patients (124 hands) with a mean age of 49.09+/-10.5 years were evaluated in this study. [Methods] Sensitivity and specificity were calculated according to two threshold values (2.83 and 3.22) and two methods, a conventional method and an internal comparison method. A threshold value of 3.22 was also used to determine sensitivity and specificity in the diagnosis of electrophysiologically moderate-to-severe carpal tunnel syndrome. Data of the first three digits were averaged to reveal the mean strength value of the monofilaments for each hand. [Results] The criteria of 2.83-conventional method yielded a sensitivity of 98% and a specificity of 17% in the diagnosis of carpal tunnel syndrome. The threshold value of 3.22 using a conventional method was found to detect moderate-to-severe carpal tunnel syndrome with high sensitivity (80%) and excellent specificity (93%). A statistically significant difference was observed in the mean strength values of the monofilaments in moderate-to-severe carpal tunnel syndrome hands and hands without carpal tunnel syndrome. [Conclusion] The current study demonstrated that Semmes-Weinstein monofilament testing might be a valuable quantitative method for detecting moderate-to-severe carpal tunnel syndrome. PMID- 26834345 TI - Comparison of the effectiveness of local corticosteroid injection and extracorporeal shock wave therapy in patients with lateral epicondylitis. AB - [Purpose] This study aimed to determine and compare the effectiveness of extracorporeal shock wave therapy and local corticosteroid injection in patients with lateral epicondylitis. [Subjects and Methods] Sixty-four patients with lateral epicondylitis were randomly divided into extracorporeal shock wave therapy and steroid injection groups. Patients were evaluated using hand grip strength, visual analog scale, and short-form McGill pain questionnaire at baseline and at 4 and 12 weeks post-treatment. [Results] Both groups showed statistically significant increase in hand grip strength and decreases on the visual analog scale and short form McGill pain questionnaire overtime. There was no statistically significant difference in the percentage of improvement in hand grip strength and on the short-form McGill pain questionnaire between groups at 4 weeks post-treatment, whereas the extracorporeal shock wave therapy group showed better results on the visual analog scale. The percentages of improvements in all 3 parameters were higher in the extracorporeal shock wave therapy group than in the injection group at 12 weeks post-treatment. [Conclusion] Both the extracorporeal shock wave therapy and steroid injection were safe and effective in the treatment of lateral epicondylitis. However, extracorporeal shock wave therapy demonstrated better outcomes than steroid injection at the long-term follow-up. PMID- 26834346 TI - Effect of activities of daily living status on resuming driving after stroke. AB - [Purpose] This study aimed to investigate the effect of the activities of daily living status on resuming driving after stroke. [Subjects] Thirty-one participants with stroke, who visited in Korean national rehabilitation centers, were included in this study. [Methods] The activities of daily living performance and the driving ability of the participants were assessed with the Korean Modified Barthel Index in combination with the results obtained by using a driving simulator. [Results] Significant correlations were noted among the Korean Modified Barthel Index, on-road driving total score, reaction time, speed anticipation tests, judgment tests, and steering wheel-pedal operation tests. Results of Stepwise multiple regression also revealed that the Korean-Modified Barthel Index total score and speed anticipation, with an R(2) of 52.9%. In other words, as the Korean-Modified Barthel Index total score and speed anticipation score increased and the driving performance score also increased in patients who had suffered a stroke. [Conclusion] The activities of daily living status was positively correlated with the patients' post stroke driving ability. PMID- 26834347 TI - Determination of the fascicle length of the gastrocnemius muscle during calf raise exercise using ultrasonography. AB - [Purpose] The purpose of this study was to find a strength training protocol which maintains isometric contraction of the triceps surae during dorsal flexion of the ankle. [Subjects] The left feet of 22 young normal volunteers who did not have orthopedic injuries or lower limb pain participated in this study. [Methods] All subjects performed four sets of five repetitions of four sets calf-raise (CR) exercise at were (1) 60 bpm without a pedestal, (2) 60 bpm with a pedestal, (3) 90 bpm without a pedestal, and (4) 90 bpm with a pedestal. The fascicle length of the lateral head of the gastrocnemius and ankle angle were measured using ultrasonography and a video camera. The CR exercise was divided into two or three phases using the kinematics of the ankle. The average change in fascicle length over the five repetitions of each phase were compared. [Results] The change of the fascicle length during the hyper-dorsiflexion phase was significantly smaller than during the other two phases. [Conclusion] It is possible that eccentric CR exercises have progressed to motor learning of the isometric contraction during counter movement, and improved the release of elastic energy of the Achilles tendon during running, jumping, and other athletic activities. PMID- 26834348 TI - Foot pressure analysis of adults with flat and normal feet at different gait speeds on an ascending slope. AB - [Purpose] This study was conducted to determine the difference in foot pressures between flat and normal feet at different gait speeds on an ascending slope. [Subjects] This study enrolled 30 adults with normal (n=15) and flat feet (n=15), with ages from 21 to 30 years old, who had no history of neurological disorders or gait problems. A treadmill was used for the analysis of kinematic features during gait, using a slope of 10%, and gait velocities of slow, normal, and fast. [Methods] A foot pressure analyzer was used to measure changes in foot pressure. [Results] Compared to the normal subjects, the foot pressure of the flatfoot subjects showed a significant increase in the 2-3rd metatarsal region with increasing gait speed, whereas there were significant decreases in the 1st toe and 1st metatarsal regions with increasing gait speed. [Conclusion] The body weight of adults with flatfoot was concentrated on the 2-3rd metatarsal region during the stance phase and increased with walking speed on the ascending slope due to weakening of function of the medial longitudinal arch. PMID- 26834349 TI - Relationship between dressing and motor function in stroke patients: a study with partial correlation analysis. AB - [Purpose] The aim of the present study was to elucidate which motor functions are most or more important for dressing performance before and after rehabilitation. [Subjects] Seventy-nine first episode stroke patients in a hospital convalescent rehabilitation ward. [Methods] The relationships between motor function of the affected upper and lower limbs, unaffected side function, trunk function, balance, cognitive function, and independence level in dressing were examined at admission and discharge using partial correlation analysis. [Results] Independence level of dressing correlated with motor function of the affected upper limb and balance at admission, but correlated only with balance at discharge. [Conclusion] Balance function was strongly associated with level of dressing independence. The effect of gross motor function of the affected upper and lower limbs on the level of independence in dressing may thus be smaller than originally expected. Enhanced balance ability can be important for learning single-handed actions of self-dressing during rehabilitation. PMID- 26834350 TI - Discomfort and muscle activation during car egress in drivers with hemiplegia following stroke. AB - [Purpose] This study investigated and compared the discomfort experienced during car egress with the car door opened at different angles and muscle activation in drivers with hemiplegia following stroke and non-disabled drivers. [Subjects and Methods] The participants were five drivers with hemiplegia and five non-disabled drivers. The discomfort experienced during car egress was measured using the nine point Likert scale when the door was opened wide and when it was opened 45 degrees . Muscle activation was measured using the TeleMyo 2400T G2 electromyography system. Electromyograph electrodes were placed on the erector spinae, rectus abdominis, and rectus femoris muscles. [Results] In the non disabled drivers, there was no significant difference in the discomforts they experienced during car egress when the door was opened wide and when it was opened 45 degrees . However, the discomfort experienced by drivers with hemiplegia when the door was opened 45 degrees was significantly higher than that experienced when it was opened wide. There was a significant difference in the activation of the erector spinae, but no difference in the activation of the rectus abdominis or rectus femoris muscles. [Conclusion] This study will help to understand the difficulties experienced by drivers with hemiplegia following stroke during car ingress and egress. PMID- 26834351 TI - Hyperthermic effects of hand bathing: benefits of incorporating finger flexion extension exercise. AB - [Purpose] The purpose of our study was to compare the effects of hand bathing using plain water and water supplemented with inorganic salt and carbonated gas and to assess the hyperthermic effects of performing finger flexion-extension exercise while bathing in water with carbonated gas and inorganic salt and without water. [Subjects and Methods] Sixteen healthy, young males were subjected to plain water bathing, CO2 bathing, kineto-CO2 bathing, or no bathing. CO2 bathing involved bathing in a solution of artificial bath additives including inorganic salts and carbon dioxide. Partial bathing of the hand was implemented for 20 minutes at 41 degrees C. The concentration of carbonic gas was set at 33 ppm. In the kineto-CO2 bathing condition, finger flexion-extension exercise was performed at 60 laps per minute in the same solution used in CO2 bathing. The control group engaged in the same exercise as those in the kineto-CO2 bathing group, but without bathing. [Results] A significant increase in deep-body temperature was observed in the CO2 bathing and kineto-CO2 bathing conditions compared with both the plain water bathing and control condition. [Conclusion] Significantly heightened hyperthermic effects were observed when finger flexion extension exercise was performed during CO2 bathing. PMID- 26834352 TI - Kinematic analysis of arm and trunk movements in the gait of Parkinson's disease patients based on external signals. AB - [Purpose] To investigate the role of external cues on arm swing amplitude and trunk rotation in Parkinson's disease. [Subjects and Methods] The subjects were 13 elderly patients with Parkinson's disease. Subjects walked under four different conditions in a random order: no cue, visual cue, auditory cue, and combined cue. The auditory cue velocity consisted of a metronome beat 20% greater than the subject's general gait speed. For the visual cue condition, bright yellow colored strips of tape placed on the floor at intervals equal to 40% of each subject's height. A motion analysis system was used to measure arm swing amplitude and trunk rotation during walking. [Results] There was a significant difference in the kinematic variables (arm swing amplitude) between different cues, but there was not a significant difference in the kinematic variables with respect to the trunk rotation. [Conclusion] The findings of this study indicate that patients with Parkinson's disease are likely to focus attention on auditory cues. The measurement of arm and trunk kinematics during gait by auditory cues can increase the available methods for the analysis of complex motor programs in movement disorders. PMID- 26834353 TI - Weight loss may be a better approach for managing musculoskeletal conditions than increasing muscle mass and strength. AB - To prevent or remedy musculoskeletal conditions, the relationship between obesity and the characteristics of muscle mass and strength need to be clarified. [Subjects and Methods] A total of 259 Japanese males aged 30-64 years were classified into 4 groups according to the Japanese obesity criteria. Body composition was evaluated, and handgrip strength and knee extensor strength were measured for the upper and lower extremities, respectively. Physical performance was evaluated with a jump test. [Results] Obesity was positively correlated with skeletal muscle mass index, percentage of whole-body fat, and leg muscle strength and negatively correlated with the percentage of muscle mass index, body weight normalized handgrip strength, and knee extensor strength, and the jump test results. [Conclusion] Weight loss may be a better approach than increasing muscle mass and strength to improve musculoskeletal conditions in obese adult males. PMID- 26834355 TI - The effects of eye coordination during deep cervical flexor training on the thickness of the cervical flexors. AB - [Purpose] The purpose of this study was to identify changes in the thicknesses of the cervical flexors according to eye coordination during deep cervical flexor training. [Subjects and Methods] Twenty normal adults were randomly selected, and during their deep cervical flexor training and eye tracking, the thicknesses of the longus colli and the sternocleidomastoid were measured using ultrasonic waves. [Results] The thickness of the longus colli statistically significantly increased when deep cervical flexor training and eye coordination were performed simultaneously. However, the thickness of the sternocleidomastoid did not show statistically significant differences according to eye coordination. [Conclusion] Eye coordination during deep cervical flexor training is likely to increase the thickness of the longus colli selectively. PMID- 26834356 TI - The effects of mental practice on unilateral neglect in patients with chronic stroke: a randomized controlled trial. AB - [Purpose] This study aims to investigate the effects of mental practice on unilateral neglect in patients with chronic stroke. [Subjects] The subjects of this study included 30 patients with chronic unilateral neglect. [Methods] The subjects were randomly divided into either the experimental group (EG) or control group (CG). All subjects received a standard rehabilitation program. In addition to the standard rehabilitation, the EG subjects received mental practice (5 days a week for 4 weeks) for 10 minutes. To compare two groups, line bisection test (LBT) and star cancellation test (SCT) were conducted. [Results] Both groups showed significant improvement in the LBT and SCT. There were statistically significant differences in the changes in LBT, but there were no significant differences in the changes in the SCT between both groups. [Conclusion] This study demonstrated that mental practice may be a valuable additional rehabilitation method in the chronic stage of neglect. PMID- 26834354 TI - Motor imagery muscle contraction strength influences spinal motor neuron excitability and cardiac sympathetic nerve activity. AB - [Purpose] The aim of this study was to investigate the changes in spinal motor neuron excitability and autonomic nervous system activity during motor imagery of isometric thenar muscle activity at 10% and 50% maximal voluntary contraction (MVC). [Methods] The F-waves and low frequency/high frequency (LF/HF) ratio were recorded at rest, during motor imagery, and post-trial. For motor imagery trials, subjects were instructed to imagine thenar muscle activity at 10% and 50% MVC while holding the sensor of a pinch meter for 5 min. [Results] The F-waves and LF/HF ratio during motor imagery at 50% MVC were significantly increased compared with those at rest, whereas those during motor imagery at 10% MVC were not significantly different from those at rest. The relative values of the F/M amplitude ratio during motor imagery at 50% MVC were significantly higher than those at 10% MVC. The relative values of persistence and the LF/HF ratio during motor imagery were similar during motor imagery at the two muscle contraction strengths. [Conclusion] Motor imagery can increase the spinal motor neuron excitability and cardiac sympathetic nerve activity. Motor imagery at 50% MVC may be more effective than motor imagery at 10% MVC. PMID- 26834357 TI - The effect of modified bridge exercise on balance ability of stroke patients. AB - [Purpose] The purpose of this study was to verify the effects of a modified bridging exercise on stroke patients with improvement in weight bearing on the affected side in standing and static balancing ability. [Subjects] Thirty patients who had a stroke were randomly allocated into a supine bridge exercise group (SBG, n=10), a supine bridge exercise on a TOGU balance pad group (SBTG, n=10), and a unilateral bridge exercise group (UBG, n=10). [Methods] The SBG patients underwent supine bridge exercise, the SBTG patients underwent supine bridge exercise with a TOGU balance pad, and the UBG patients underwent unilateral bridge exercise. All groups received 20 minutes of training per day, five times per week, for four weeks. [Results] All groups showed significant changes in weight bearing in a standing position after the intervention. The SBTG and UBG groups showed significant changes in balance ability. [Conclusion] According to the results of this study, bridge exercise was effective in improving weight bearing in a standing position and improving balance on stroke patients. The bridge exercise with a TOGU balance pad and the unilateral bridge exercise were especially more effective in anterior, posterior length in limit of stability following on standing. PMID- 26834358 TI - Comparison of skin sensory thresholds using pre-programmed or single-frequency transcutaneous electrical nerve stimulation. AB - [Purpose] The purpose of the present study was to compare the sensory thresholds of healthy subjects using pre-programmed or single-frequency transcutaneous electrical nerve stimulation. [Subjects] Ninety healthy adult subjects were randomly assigned to pre-programmed or single-frequency stimulation groups, each consisting of 45 participants. [Methods] Sensory thresholds were measured in the participants' forearms using von Frey filaments before and after pre-programmed or single-frequency transcutaneous electrical nerve stimulation, and the result in values were analyzed. [Results] Significant increases in sensory threshold after stimulation were observed in both groups. However, there were no significant differences between the two groups in sensory thresholds after stimulation or in the magnitude of threshold increases following stimulation. [Conclusion] Our results show that there are no differences between sensory threshold increases induced by pre-programmed and single-frequency transcutaneous electrical nerve stimulation. PMID- 26834359 TI - The effects of gluteus muscle strengthening exercise and lumbar stabilization exercise on lumbar muscle strength and balance in chronic low back pain patients. AB - [Purpose] The aim of this study was to examine the effects of exercise to strengthen the muscles of the hip together with lumbar segmental stabilization exercise on the lumbar disability index, lumbar muscle strength, and balance. [Subjects and Methods] This study randomly and equally assigned 40 participants who provided written consent to participate in this study to a lumbar segmental stabilization exercise plus exercise to strengthen the muscles of the gluteus group (SMG + LES group) and a lumbar segmental stabilization exercise group. [Results] Each evaluation item showed a statistically significant effect. [Conclusion] Clinical application of exercise in this study showed that lumbar segmental stabilization exercise plus exercise to strengthen the muscles of the gluteus resulted in a greater decrease in low back pain disability index and increase in lumbar muscle strength and balance ability than lumbar segmental stabilization exercise in chronic low back pain patients receiving the exercise treatments during the same period. PMID- 26834360 TI - Effect of high-intensity pulse irradiation with linear polarized near-infrared rays on muscle tone in patients with cerebrovascular disease: a randomized controlled trial. AB - [Purpose] This study evaluated effects of a high-intensity linear polarized near infrared ray irradiation for mitigation of muscle hypertonia. [Subjects] The subjects were 20 patients with cerebrovascular disease. [Methods] Subjects were randomly allocated to an intervention or control group. The intervention group received irradiation of the triceps surae. Passive range of motion and passive resistive joint torque of ankle dorsiflexion were measured before and after the intervention in knee extended and flexed positions. [Results] In the knee extended position, the mean changes in passive range of motion were 2.70 degrees and -0.50 degrees in the intervention and control groups, respectively, and the mean changes in passive resistive joint torque were -1.42 and -0.26 N.m in the intervention and control groups, respectively. In the knee flexed position, the mean changes in passive range of motion were 3.70 degrees and 0.70 degrees in the intervention and control groups, respectively, and the mean changes in passive resistive joint torque were -2.38 and -0.31 N.m in the intervention and control groups, respectively. In both knee positions, the mean changes in the two indices were greater in the intervention group than in the control group. [Conclusion] High-intensity linear polarized near-infrared ray irradiation increases passive range of motion and decreases passive resistive joint torque. PMID- 26834361 TI - The influence of fathers' parenting participation with disabled children on parenting stress in mothers. AB - [Purpose] The purpose of this research was two-fold: (1) to evaluate the effects of father's parenting participation on parenting stress among mothers with disabled children and (2) more specifically, to investigate the importance of fathers' parenting participation in decreasing mothers' parenting stress. [Subjects and Methods] To examine these relationships, this study recruited 82 mothers with disabled children from rehabilitation centers in the Gwangju city. The common characteristics of parents and children, father's parenting participation, and mother's parenting stress were assessed using standard questionnaires. [Results] Based on mother reports, findings suggest that as fathers' parenting participation increases mothers' parenting stress decreases. [Conclusion] The present study reveals a need for improvement in parenting education and in providing fathers of disabled children with a temporary leave of absence from work. Specifically, this research highlights the importance of shared parenting responsibilities among family members. Finally, our findings suggest that developing a standardized national program for assisting parents with disabled children may help decrease parenting stress in mothers. PMID- 26834362 TI - An effective model for observational learning to improve novel motor performance. AB - [Purpose] To investigate whether for observational learning involving a ball rotation task, an unskilled model showing clumsy finger movements is more effective than a skilled model?. [Subjects and Methods] Thirty-six young adults were randomly assigned to one of three groups. The unskilled model observation group observed a video of a ball rotation task practiced by a person for a short time. The skilled model observation group observed another video of the same task practiced by the person for a relatively long time. The non-observation group did not observe any video. Regarding rotation speed, the unskilled model was faster than the participants' but slower than the skilled model. The unskilled model had the highest number of ball drops. [Results] After the observation, the unskilled model observation group showed significantly faster rotation speed than the other groups. There were no significant differences between the groups in the number of ball drops. [Conclusion] An unskilled model whose performance is better than the participants' is beneficial for improving motor performance but a model showing less skill than the participants is not. PMID- 26834363 TI - Effects of shoe type on lower extremity muscle activity during treadmill walking. AB - [Purpose] The purpose of this study was to analyze the effects of different shoe types on lower extremity muscle activity in healthy young women by using electromyography. [Subjects and Methods] Fifteen healthy young women in their 20s were included in this single-group repeated measures study. The subjects were divided into three groups: Converse sneakers, rain boots, and combat boots. The subjects walked on a treadmill at 4 km/h for 30 min, during which six muscles were examined using electromyography: the rectus femoris, vastus medialis, semimembranosus, tibialis anterior, peroneus longus, and medial head of the gastrocnemius. Between switching shoe types, a 24-h rest period was instated to prevent the fatigue effect from treadmill walking. [Results] One-way analysis of variance used to compare electromyography results among the three groups showed that the main effect of group differed significantly for the vastus medialis. Vastus medialis activity was higher in the rain boots group than the Converse sneakers group, and it was higher in the combat boots group than rain boots group. [Conclusion] Shoe type affects lower extremity muscle activity. Our findings may help individuals choose the ideal shoes for daily walking. PMID- 26834364 TI - Differences in understanding and subjective effects of home-visit rehabilitation between user families and rehabilitation providers. AB - [Purpose] This study aimed to clarify differences in understanding and subjective effects of home-visit rehabilitation between user families and rehabilitation providers. [Subjects] The subjects were home-visit rehabilitation providers and user families. [Methods] Home-visit rehabilitation providers and user families completed a self-administered questionnaire regarding the content and subjective effects of home-visit rehabilitation. For statistical analysis, the McNemar's test was used. [Results] Fifty pairs of responses met the inclusion criteria. The mean age of user families was 65.0 +/- 11.2 years, and 58.0% (29/50) were spouses of users (user mean age, 77.7 +/- 10.2 years; 48.0% (24/50) female). With regard to home-visit rehabilitation content, user families thought that paralysis improvement exercise, massage, and self-care activities were implemented to a greater degree than did rehabilitation providers. With regard to the subjective effects of home-visit rehabilitation, a higher proportion of user families noticed "maintenance/improvement" effects on symptoms and sequelae, as well as pain and suffering, compared with providers. [Conclusion] User families believed that rehabilitation would also improve users' symptoms and pain. Care providers should explain the aims of home-visit rehabilitation to users and their families, both of which require a strong understanding of home-visit rehabilitation in order to achieve rehabilitation goals. PMID- 26834365 TI - The effect of lumbar stabilization exercises and thoracic mobilization and exercises on chronic low back pain patients. AB - [Purpose] To investigate whether pain, balance, and stabilization of the lumbar region can be improved through thoracic mobilization in addition to lumbar stabilizaing exercises. [Subjects and Methods] This study recruited 36 subjects with chronic low back pain lasting more than 12 weeks. The subjects recruited for this study participated voluntarily, and provided their signed consent to participation. [Results] Improvement in balance was largest in the lumbar stabilization exercise group, followed by the thoracic mobilization and exercise group, and the traditional physical therapy group, in decreasing order of effect. [Conclusion] In conclusion, lumbar stabilization exercises combined with thoracic mobilization had greater effects on stabilization of the lumbar region pain relief, and improvement of the function of the patients with chronic low back pain. PMID- 26834366 TI - Sex differences in knee strength deficit 1 year after anterior cruciate ligament reconstruction. AB - [Purpose] Little is known about the outcome differences between men and women after anterior cruciate ligament (ACL) reconstruction. Therefore, the present study aimed to compare knee muscle strength between men and women 1 year after ACL reconstruction. [Subjects and Methods] Retrospective and outcome study. Between 2012 and 2015, 35 males (mean age, 29.7 +/- 010.7 years) and 35 females (mean age, 28.2 +/- 11.3 years) who had undergone primary ACL reconstruction were recruited from Samsung medical centers. We assessed the strength deficit in the quadriceps (extensor) and hamstrings (flexor) at 60 degrees /sec and 180 degrees /sec with isokinetic testing equipment. Statistical analysis was conducted with a t-test to determine if sex differences existed in knee strength deficit. [Results] Significant differences were noted between men and women with respect to extensor muscle strength deficit. Women reported less extensor muscle strength than men did, at the angular velocities 60 degrees /sec and 180 degrees /sec. However, no significant sex differences were found at either velocity with respect to the strength deficit of the knee flexor muscles. [Conclusion] Compared to male patients, female patients reported significantly less extensor muscle strength and less improvement 1 year after reconstruction. PMID- 26834367 TI - The effect of thoracic spine mobilization and stabilization exercise on the muscular strength and flexibility of the trunk of chronic low back pain patients. AB - [Purpose] To investigate whether thoracic spine mobilization added to stabilization exercises increases the muscular strength and range of motion of the thoracic vertebrae of chronic low-back pain patients. [Subjects] This study enrolled 20 patients with chronic low back pain, who were divided into two groups. Ten subjects were randomly selected for the stabilization exercise group and the remaining 10 subjects received thoracic spine mobilization in addition to performing the stabilization exercises. [Methods] The patients performed stabilization exercises and received thoracic spine mobilization for 12 weeks. The range of motion and isometric muscular strength of the vertebrae of all subjects were measured before and after the intervention. [Results] In the comparison of muscular strength before and after the intervention, the change in muscular strength of the trunk flexors in the stabilization exercise group was 16.0+/-7.4 Nm, and that of the thoracic spine mobilization group was 34.2+/-7.6 Nm, a significant difference in each group. In the post-intervention intergroup comparison, the muscular strength of trunk flexors in the stabilization exercise group was 111.1+/-16.9 Nm, while that of the thoracic spine mobilization group was 125.9+/-11.3 Nm, a significant difference. Also, the muscular strength of the trunk extensors in the stabilization exercise group was 148.9+/-31.8 Nm, while that of the thoracic spine mobilization group was 182.9+/-37.2 Nm, a significant difference. The thoracic spine flexion in the stabilization exercise group was 29.8+/-9 degrees, while that of the thoracic spine mobilization group was 38.7+/ 6.9 degrees, a significant difference. However, there was no significant difference in lumbar flexion values between the two groups. [Conclusion] Thoracic spine mobilization added to a stabilization exercise increased the muscular strength of patients with chronic low back pain. PMID- 26834368 TI - Balance training using an interactive game to enhance the use of the affected side after stroke. AB - [Purpose] Stroke and other cerebrovascular diseases are major causes of adult mobility problems. Because stroke immobilizes the affected body part, balance training uses the healthy body part to complete the target movement. The muscle utilization rate on the stroke affected side is often reduced which further hinders affected side functional recovery in rehabilitation. [Subjects and Methods] This study tested a newly-developed interactive device with two force plates to measuring right and left side centers of pressure, to establish its efficacy in the improvement of the static standing ability of patients with hemiplegia. An interactive virtual reality game with different side reaction ratios was used to improve patient balance. The feasibility of the proposed approach was experimentally demonstrated. [Results] Although the non-affected side is usually used to support the body weight in the standing position, under certain circumstances the patients could switch to using the affected side. A dramatic improvement in static standing balance control was achieved in the eyes open condition. [Conclusion] The proposed dual force plate technique used in this study separately measured the affected and non-affected-side centers of pressure. Based on this approach, different side ratio integration was achieved using an interactive game that helped stroke patients improve balance on the affected side. Only the patient who had suffered stroke relatively recently benefited significantly. The proposed technique is of little benefit for patients whose mobility has stagnated to a certain level. PMID- 26834369 TI - Effectiveness of platelet-rich plasma in the treatment of moderate knee osteoarthritis: a randomized prospective study. AB - [Purpose] To assess the effects of different numbers of platelet-rich plasma (PRP) applications on pain and physical function in grade 3 knee osteoarthritis (OA). [Subjects and Methods] A total of 102 patients with grade 3 knee OA were randomly divided into three groups: Group 1 received a single injection of PRP, Group 2 received two injections of PRP two weeks apart, Group 3 received three injections of PRP at 2-weeks intervals. All patients were evaluated with a visual analog scale (VAS), the Western Ontario and McMaster Universities Arthritis Index (WOMAC), and the Timed-Up and Go test (TUG) before the treatment and at 1, 3 and 6 months after the treatment. [Results] Ninety-eight patients (15 males, 83 females) completed the study. The mean ages of the patients were 53.5+/-6.6, 54.9+/-5.3, and 55.1+/-5.6 years in Group 1, Group 2, and Group 3, respectively. Statistically significant improvements were noted in all of the evaluated measures in all of the groups. The mean differences of Group 1-Group 2 and Group 1-Group 3 WOMAC total, WOMAC pain, WOMAC stiffness, and WOMAC function scores were statistically significant. [Conclusion] PRP is an effective treatment for functional status and pain in moderate knee osteoarthritis and a minimum of two injections is appropriate. PMID- 26834370 TI - The effects of trunk stabilization exercise on bone density after menopause. AB - [Purpose] This study examined the effect of low intensity exercise on bone density by conducting trunk stabilization exercise on females after menopause for 24 weeks. [Subjects and Methods] Thirty three female subjects over 47 years old and under the age of 53 were selected and 16 for experimental group and 17 for control group were randomly selected. Experimental group had performed spinal and pelvic stabilization exercise 30 minutes a day, 5times a week, for 24 weeks. Except for the daily life, control group did not participate in any characteristic movement. Bone density of every member in experimental group was measured using average value of bone density of 1st-4th lumbar through quantitative computer tomography. [Results] There was a meaningful difference in only control group about measured value of bone density within each group, experimental and control group, but there was no meaningful difference in measured value of bone density between two groups, experimental group and control group. [Conclusion] Through this research, we could see the fact that although trunk stability exercise could not change bone density meaningfully, it could maintain bone density. In the future, it is randomly necessary to study things related this because results of researches can show different results according to exercise intensity, exercise period, age, weight, hormone status and mediation period. It is considered that it will help to prevent and treat patients with osteoporosis a lot. PMID- 26834371 TI - Effect of leg press training on patellar realignment in patients with patellofemoral pain. AB - [Purpose] The purpose of this study was to investigate the effect of leg press and leg press with hip adduction exercise training on patellar alignment and pain in patients with patellofemoral pain (PFP). [Subjects and Methods] Seventeen patients participated in this study. Eight weeks of leg press or leg press with hip adduction training, including progressive lower-limb weight-training and stretching, was given. Patellar alignment (tilt and displacement) and pain measurements were conducted before and after leg press or leg press with hip adduction training. Patellar tilt angle and the bisect offset index were measured on axial computed tomography scans of the fully extended knee position with the quadriceps relaxed and contracted. Pain was assessed by using a 10-cm visual analog scale. [Results] No differences were found in patellar tilt and displacement with the quadriceps either relaxed or contracted after leg press and leg press with hip adduction. However, significant pain reduction was evident in both leg press and leg press with hip adduction. [Conclusion] The results indicated that patellar realignment does not appear to mediate pain alleviation. Furthermore, hip adduction in addition to leg press training had no additive beneficial effect on patellar realignment or pain reduction. PMID- 26834372 TI - The effect of Swiss ball exercise and resistance exercise on balancing ability of scoliosis patients. AB - [Purpose] The purpose of the study was to closely examine the efficiency of Swiss ball exercise and resistance exercise in improving the on the static balancing ability by applying them to patients with scoliosis and to compare the effects of the interventions. [Subjects] Forty scoliosis patients were divided into a Swiss ball exercise group (SEG, N = 20) and a Resistance exercise group (REG, N = 20) randomly. [Methods] SEG conducted chest stretching, trunk exercise using the Swiss ball. REG conducted chest stretching, trunk exercise with therapist's resistance. Both groups received training 30 min per day, five times per week, for eight weeks. [Results] Both SEG and REG showed significant differences between pre- and post-mediation in terms of weight distribution, sway area, sway length, sway speed, and limit of stability. Sway speed and limit of stability had increased more significantly in REG than in SEG. [Conclusion] According to the result of this study, both Swiss ball exercise and chest Resistance exercise were effective for improving on the static balancing ability. But we suggest resistance exercise is more efficient to increase of sway speed, limit of stability. PMID- 26834373 TI - The relationship between energy cost and the center of gravity trajectory during sit-to-stand motion. AB - [Purpose] The purpose of this study was to examine the relationship between jerk cost and the formation of the center of gravity trajectory during sit-to-stand motion with asymmetrical foot placement. [Subjects] Nineteen male volunteers were included (age: 21 +/- 1 years). [Methods] The subjects moved from a sitting position to a standing position under two different foot placement conditions: (1) 0 degrees of dorsiflexion on the non-dominant side and 20 degrees of dorsiflexion on the dominant side (P1) and (2) 20 degrees of plantarflexion on the non-dominant side and 20 degrees of dorsiflexion on the dominant side (P2). Two standing conditions were used: (1) natural movement and (2) instructed movement, with instructions to increase weight bearing on the non-dominant side. The center of gravity trajectory and its jerk cost were calculated at each axis: front and back (jerk-x), right and left (jerk-y), and vertical (jerk-z). [Results] Jerk-x and jerk-y were significantly larger during instructed movement than natural movement in both P1 and P2. Jerk-z was not significantly different between instructed and natural movement in P1 or P2. [Conclusion] These results indicate that energy cost influences the formation of the center of gravity trajectory during sit-to-stand motion with asymmetrical foot placement. PMID- 26834374 TI - The effect of SSP therapy on elderly nursing home residents' chronic constipation. AB - [Purpose] The aim of the present study is to examine the effects of silver spike point therapy on elderly persons' chronic constipation. [Subjects and Methods] The subjects of the present study were 30 elderly chronic-constipation sufferers who resided in a nursing home and had other physical conditions that necessitated wheelchair ambulation. There were three test groups in the present study: an silver spike point group, an acupuncture group, and a control group; 10 subjects were assigned to each group. The silver spike point group and the acupuncture group received their respective interventions, which were applied to both sides of the Tiensu for 20 minutes per day, five days per week, over a four week period. Weekly bowel movement frequency was recorded, and the Constipation Assessment Scale and Bowel Function Assessment Form were used as data-gathering instruments. [Results] Following treatment, the silver spike point and acupuncture groups showed significant improvement, based on the Constipation Assessment Scale and the Bowel Function Assessment Form, compared with the control group. [Conclusion] Based on the above results, silver spike point therapy can be administered to alleviate chronic constipation in elderly nursing home residents who cannot walk independently due to declining physical functions. PMID- 26834375 TI - Comparison of cortical activation in an upper limb added-purpose task versus a single-purpose task: a near-infrared spectroscopy study. AB - [Purpose] The purpose of this study was to compare prefrontal activations during an added-purpose task with those during a single-purpose task using functional near-infrared spectroscopy. [Subjects] Six healthy right-handed adults were included in this study. [Methods] The participants were instructed to complete both added-purpose and single-purpose activities separately with each hand. The near-infrared spectroscopy probes were placed on the scalp overlying the prefrontal cortex, according to the International 10-20 system (Fz). Changes in the oxygenated hemoglobin and deoxygenated hemoglobin concentrations in the prefrontal cortex were measured during performance of the activities. We then compared the number of activation channels with significant increase in oxygenated hemoglobin, during added-purpose activity to single-purpose activity using both hands separately. [Results] A greater number of widespread activations were observed in the prefrontal cortex during the added-purpose task than during the single-purpose task. These results were noted with both right and left hands. [Conclusion] According to our findings, added-purpose activity can bring about more activation in the prefrontal cortex, which may provide occupational therapists with effective guides in therapeutic practice. PMID- 26834376 TI - The correlation between calcaneal valgus angle and asymmetrical thoracic-lumbar rotation angles in patients with adolescent scoliosis. AB - [Purpose] This study aimed to provide a predictable evaluation method for the progression of scoliosis in adolescents based on quick and reliable measurements using the naked eye, such as the calcaneal valgus angle of the foot, which can be performed at public facilities such as schools. [Subjects and Methods] Idiopathic scoliosis patients with a Cobb's angle of 10 degrees or more (96 females, 22 males) were included in this study. To identify relationships between factors, Pearson's product-moment correlation coefficient was computed. The degree of scoliosis was set as a dependent variable to predict thoracic and lumbar scoliosis using ankle angle and physique factors. Height, weight, and left and right calcaneal valgus angles were set as independent variables; thereafter, multiple regression analysis was performed. This study extracted variables at a significance level (alpha) of 0.05 by applying a stepwise method, and calculated a regression equation. [Results] Negative correlation (R=-0.266) was shown between lumbar lordosis and asymmetrical lumbar rotation angles. A correlation (R=0.281) was also demonstrated between left calcaneal valgus angles and asymmetrical thoracic rotation angles. [Conclusion] Prediction of scoliosis progress was revealed to be possible through ocular inspection of the calcaneus and Adams forward bending test and the use of a scoliometer. PMID- 26834377 TI - The effects of non-elastic taping on muscle tone in stroke patients: a pilot study. AB - [Purpose] Hemiplegia occurs when posturing with a dominant flexor tone is present in the upper limbs, thus preventing increased abnormal tone. We attempted to improve the side effects of this condition using elbow re-positioning with non elastic tape; this method is used to modulate abnormal muscle tone in chronic hemiplegic stroke patients. [Subjects and Methods] Fourteen post-stroke patients were included in this study. Non-elastic tape was applied to the elbow joint in a spiral manner. Before and after the tape was applied, the degree of spasticity (hypertonia) was measured in the elbow flexor muscles using the Modified Ashworth Scale (MAS). Global synkinesis (GS) intensity using electromyography (EMG) was measured in the biceps brachii and triceps brachii during voluntary isometric elbow contractions of the contralateral upper limbs. [Results] Application of non elastic tape at the elbow joint significantly changed the GS intensity, but no significant changes were found when compared with the MAS. [Conclusion] This study demonstrates that non-elastic tape can be used to decrease abnormal elbow flexor tone. The findings may be used to influence the choice of intervention regarding muscle tone and spastic elbow flexion. PMID- 26834378 TI - Evaluation of the effects of different treatments for the elbow joint using joint proprioception and surface electromyography. AB - [Purpose] The purpose of this study was to examine the immediate effects of strength training and neuromuscular joint facilitation (NJF) distal resistance training on muscle strength and proprioception. [Subjects] The subjects were 15 young healthy people (29.3+/-4.1 y, 166.8+/-7.1 cm, 62.4 +/- 11.6 ky). [Methods] Two isometric contraction techniques were applied on the elbow joint: elbow joint flexion muscle strength training (MST) and the elbow joint flexion pattern of NJF. Muscle strength (measured by surface electromyography [sEMG]) and joint position errors of the left upper limb were measured before and after one intervention session of MST and NJF. [Results] The decrease in error in elbow flexion angle repetition represented the improvement resulting from NJF. sEMG of the biceps brachii showed significant increases in the maximum discharge and average discharge after the intervention. [Conclusion] This result suggests that elbow joint proprioception and muscle strength can be improved by NJF together with proximal resistance training. PMID- 26834379 TI - Association between handgrip strength and cognitive impairment in elderly Koreans: a population-based cross-sectional study. AB - [Purpose] The purpose of this study was to investigate the association between handgrip strength and mild cognitive impairment in elderly adults. [Subjects] Study participants included 2,982 adults (1,366 males and 1,616 females), aged 65 years or older. [Methods] This population-based cross-sectional study used the baseline database from the Korean Longitudinal Study of Ageing. [Results] The odds ratio for mild cognitive impairment showed a significant linear decrease in relation to the quartile of handgrip strength, independent of potential covariates, in both men and women. Moreover, after excluding incident cases of mild cognitive impairment, the results showed that greater handgrip strength was associated with higher cognitive function scores in the elderly. [Conclusion] The findings presented here suggest that handgrip strength is associated with a risk of mild cognitive impairment in the Korean elderly. Moreover, greater handgrip strength is associated with higher cognitive function in cognitively normal elderly individuals. PMID- 26834380 TI - Reference values for the Y Balance Test and the lower extremity functional scale in young healthy adults. AB - [Purpose] This study aimed to establish gender-specific reference values for the Y Balance Test (YBT) and the Arabic version of the Lower Extremity Functional Scale (LEFS-Ar) in healthy young adults in Saudi Arabia, and to examine gender differences in the YBT and LEFS-Ar values. [Subjects and Methods] Healthy young adults (31 females, 30 males) completed the YBT and LEFS-Ar in 1 test session. Descriptive statistical analysis (mean, standard deviation, 95% confidence interval) was used to compute the YBT and LEFS-Ar reference values. Independent t tests were used to examine gender differences in the YBT and LEFS-Ar values. [Results] Gender-specific reference values were obtained for the right, left, dominant, and non-dominant leg as well as for the average performance of both the legs. males showed greater YBT normalized reach distances than females did in the anterior, posteromedial, and posterolateral directions; furthermore, males showed higher YBT composite scores than females did. However, the LEFS-Ar values did not differ between males and females. [Conclusion] Gender-specific reference values were obtained for the YBT and LEFS-Ar in healthy young adults in Saudi Arabia. males performed better than females did in the YBT. However, no gender differences were noted in LEFS-Ar. PMID- 26834381 TI - Acute effects of unilateral whole body vibration training on single leg vertical jump height and symmetry in healthy men. AB - [Purpose] The aim of the present study was to investigate the acute effects of unilateral whole body vibration training on height and symmetry of the single leg vertical jump in healthy men. [Subjects] Thirty males with no history of lower limb dysfunction participated in this study. [Methods] The participants were randomly allocated to one of three groups: the unilateral vibratory stimulation group (n=10), bilateral vibratory stimulation group (n=10), and, no vibratory stimulation group (n=10). The subjects in the unilateral and bilateral stimulation groups participated in one session of whole body vibration training at 26 Hz for 3 min. The no vibratory stimulation group subjects underwent the same training for 3 min without whole body vibration. All participants performed the single leg vertical jump for each lower limb, to account for the strong and weak sides. The single leg vertical jump height and symmetry were measured before and after the intervention. [Results] The single leg vertical jump height of the weak lower limb significantly improved in the unilateral vibratory stimulation group, but not in the other groups. The single leg vertical jump height of the strong lower limb significantly improved in the bilateral vibratory stimulation group, but not in the other groups. The single leg vertical jump symmetry significantly improved in the unilateral vibratory stimulation group, but not in the other groups. [Conclusion] Therefore, the present study found that the effects of whole body vibration training were different depending on the type of application. To improve the single leg vertical jump height in the weak lower limbs as well as limb symmetry, unilateral vibratory stimulation might be more desirable. PMID- 26834382 TI - Effects of external focus of attention on balance: a short review. AB - [Purpose] The present study reviewed studies that examined the effects of attentional focus on balance. [Methods] Keywords such as "attentional", "focus", and "balance" were used to find relevant research papers in PubMed (www.ncbi.nlm.nih.gov/pubmed). Forty-five papers were found, and 18 of them were used for this study, excluding review papers and papers irrelevant to the topic of this study. [Results] Among the papers used for the review, the number of papers in which external focus produced effective outcomes was 15 (83.3%). The number of papers in which both external and internal focus produced effective outcomes was 2 (11.1%). The number of paper in which no instruction about attentional focus was effective was 1 (5.5%), and the number of papers in which internal focus was effective was zero. [Conclusion] This short review suggests clinical implications about how physical therapists can use attentional focus for balance rehabilitation of patients. Instructions about external focus of attention can generally be useful as a method to improve posture and balance control. Furthermore, the present reviews indicates that external focus of attention would be more useful in a rehabilitation stage in which the difficulty level of balance performance is gradually increased. PMID- 26834383 TI - Therapeutic physical exercise in neural injury: friend or foe? AB - [Purpose] The intensity of therapeutic physical exercise is complex and sometimes controversial in patients with neural injuries. This review assessed whether therapeutic physical exercise is beneficial according to the intensity of the physical exercise. [Methods] The authors identified clinically or scientifically relevant articles from PubMed that met the inclusion criteria. [Results] Exercise training can improve body strength and lead to the physiological adaptation of skeletal muscles and the nervous system after neural injuries. Furthermore, neurophysiological and neuropathological studies show differences in the beneficial effects of forced therapeutic exercise in patients with severe or mild neural injuries. Forced exercise alters the distribution of muscle fiber types in patients with neural injuries. Based on several animal studies, forced exercise may promote functional recovery following cerebral ischemia via signaling molecules in ischemic brain regions. [Conclusions] This review describes several types of therapeutic forced exercise and the controversy regarding the therapeutic effects in experimental animals versus humans with neural injuries. This review also provides a therapeutic strategy for physical therapists that grades the intensity of forced exercise according to the level of neural injury. PMID- 26834384 TI - Low-level laser therapy for the treatment of superficial thrombophlebitis after chemotherapy in breast cancer patients: a case study. AB - [Purpose] We report the case of a breast cancer patient with superficial thrombophlebitis treated with low-level laser therapy. [Case] The patient was a 66-year-old women who developed superficial thrombophlebitis in the left upper limb after chemotherapy. She was administered 6 sessions of low-level laser therapy. [Result] Her pain score decreased by 8 points. Her scores on the Patient and Observer scar Assessment Scale decreased by 18 points for the observer portion and by 26 points for the patient portion. [Conclusion] Low-level laser therapy is effective for the reduction of pain and the size of scar tissue in patients with superficial thrombophlebitis. PMID- 26834385 TI - Effects of a self-assessment device for pelvic position on chronic back pain and range of motion of the trunk. AB - [Purpose] The purpose of the present study was to investigate the effects of a self-assessment device for pelvic position in a computer user with back pain. [Subjects] A 37-year-old man who complained of low back pain at L3-5 levels was the participant. [Methods] In this study, a self-assessment device for the pelvic position was developed. The patient was instructed in self-assessment of the pelvic position and an exercise program for two months. Prior to this instruction, the visual analog scale score and range of motion of the trunk were assessed. [Results] After the instruction in self-assessment of the pelvic position and exercise program, the visual analog scale score decreased from 7 to 3, and trunk flexion, extension, and bilateral lateral flexion range of motion were increased compared to the initial assessment. [Conclusion] Therefore, use of self-anthropometers and measuring methods in patients with chronic back pain is considered an important area of study. PMID- 26834386 TI - The effects of prism glasses and intensive upper limb exercise on hemineglect, upper limb function, and activities of daily living in stroke patients: a case series. AB - [Purpose] This study aimed to examine the effects of visual field with prism glasses, and intensive upper limb functional training on reduction of hemineglect and improvement in upper limb function and activities of daily living in three stroke patients with hemineglect. [Subjects] This study included three stroke patients hospitalized in a sanatorium. [Methods] Intervention treatment involving prism glass use for 12 hours and 30 minutes and paretic side upper limb training was conducted 5 days a week for 15 weeks. Three upper limb training tasks (hitting a balloon, passing through a ring, and reading a newspaper) were performed for 10 minutes each session, for a total of 30 minutes. Line by Section, Motor-Free Visual Perception Test-3 (MVPT-3), Manual Function Test (MFT), Box & Block Test (BBT), and Assessment of Motor and Process Skills (AMPS) were conducted before and after intervention. [Results] Subjects' hemineglect decreased and upper limb function on the paretic side improved after intervention, which enhanced activities of daily living. [Conclusion] Prism glass use and paretic upper limb functional training effectively ameliorated stroke patients' hemineglect and improved upper limb function. Future research should focus on prism glasses that provide a wide visual field for use in patients with different conditions. PMID- 26834387 TI - Effects of modified constraint-induced movement therapy and functional bimanual training on upper extremity function and daily activities in a patient with incomplete spinal cord injury: a case study. AB - [Purpose] In this study, we examined effects of modified constraint-induced movement therapy (m-CIMT) and functional bimanual training, when applied to a patient with incomplete spinal cord injury, on upper extremity function and daily activities. [Subject and Methods] One patient, diagnosed with C4 incomplete spinal cord injury, underwent physical therapy with constraint-induced movement therapy for 3 hours and task-oriented bimanual training for 1 hour, per day. This combined 4-hour session was performed five times a week, for 3 weeks, totaling 15 sessions. Upper extremity function was measured using the Manual Function Test (MFT) and Box & Block Test (BBT). Additionally, Spinal Cord Independence Measure Version III (SCIM-III) and Short Form 36 Health Survey (SF-36) were used to assess functional outcomes. [Results] Mobility of the hand and overall function of upper extremities were enhanced following intervention. Moreover, the subject's quality of life and ability to carry out daily activities also improved. [Conclusion] Modified constraint-induced movement therapy and bimanual training was effective in enhancing upper extremity function and performance of daily routines in a patient with incomplete spinal cord injury. Further studies, recruiting multiple subjects, should focus on m-CIMT using diverse methods, performed during the course of daily activities. PMID- 26834388 TI - Effects of using a device for self-measurement of cervical ROM on neck pain of computer user. AB - [Purpose] The purpose of this study was to investigate the effects of using a device for the self-measurement of cervical range of motion on neck pain experienced by a computer user. [Subject] A 39-year-old male subject with neck pain caused by working on a computer was selected for the study. [Methods] The instrument was developed for the study, and that the instrument is used to self measure cervical range of movement. The subject was trained in self-measurement procedures and a self-exercise program for two months, and pain was controlled through self-assessment and a program. The pressure pain threshold for the upper trapezius muscle, and cervical ranges of motion were measured prior to and after the 2-month period of pain control. [Results] At the conclusion of self measurement and the self-exercise program, the pressure pain threshold was higher than the initial pressure pain threshold, and all cervical ranges of motion increased compared to the initial cervical ranges of motion. [Conclusion] This result shows that the self-management device for cervical ROM is an effective tool for pain management for computer users with cervical pain. PMID- 26834389 TI - Heat-up Synthesis of Ag-In-S and Ag-In-S/ZnS Nanocrystals: Effect of Indium Precursors on Their Optical Properties. AB - Cadmium-free I-III-VI nanocrystals (NCs) have recently attracted much research interests due to their excellent optical properties and low toxicity. In this work, with a simple heat-up synthetic system to prepare high quality Ag-In-S (AIS) NCs and their core/shell structures (AIS/ZnS NCs), we investigated the effect of different indium precursors (indium acetate and indium chloride) on NC optical properties. The measurements on photoluminescence spectra of AIS NCs show that the photoluminescence peak-wavelength of AIS NCs using indium acetate is in the range from 596 to 604 nm, and that of AIS NCs using indium chloride is from 641 to 660 nm. AIS and AIS/ZnS NCs using indium acetate present around 15% and 40% QYs, and both AIS and AIS/ZnS NCs using indium chloride present around 31% QYs. The photoluminescence decay study indicates that the lifetime parameters of AIS and AIS/ZnS using indium chloride are 2 ~ 4 times larger than those of AIS and AIS/ZnS NCs using indium acetate. Moreover, AIS NCs using indium chloride have a slower photobleaching dynamics than AIS NCs using indium acetate, and ZnS shell coating on both types of AIS NCs significantly enhances their photostability against UV exposure. We believe that the unique optical properties of AIS and AIS/ZnS NCs will open an avenue for these materials to be employed in broad electronic or biomedical applications. PMID- 26834390 TI - Design and development of a dust dispersion chamber to quantify the dispersibility of rock dust. AB - Dispersible rock dust must be applied to the surfaces of entries in underground coal mines in order to inert the coal dust entrained or made airborne during an explosion and prevent propagating explosions. 30 CFR. 75.2 states that "... [rock dust particles] when wetted and dried will not cohere to form a cake which will not be dispersed into separate particles by a light blast of air ..." However, a proper definition or quantification of "light blast of air" is not provided. The National Institute for Occupational Safety and Health (NIOSH) has, consequently, designed a dust dispersion chamber to conduct quantitative laboratory-scale dispersibility experiments as a screening tool for candidate rock dusts. A reproducible pulse of air is injected into the chamber and across a shallow tray of rock dust. The dust dispersed and carried downwind is monitored. The mass loss of the dust tray and the airborne dust measurements determine the relative dispersibility of the dust with respect to a Reference rock dust. This report describes the design and the methodology to evaluate the relative dispersibility of rock dusts with and without anti-caking agents. Further, the results of this study indicate that the dispersibility of rock dusts varies with particle size, type of anti-caking agent used, and with the untapped bulk density. Untreated rock dusts, when wetted and dried forming a cake that was much less dispersible than the reference rock dust used in supporting the 80% total incombustible content rule. PMID- 26834392 TI - An appraisal of a technical modification for prevention of bladder neck stenosis in retropubic prostatectomy: An initial report. AB - OBJECTIVE: To report the experience with our technical modification of the trigone-bladder neck complex management in the prevention of bladder neck stenosis (BNS) following open simple retropubic prostatectomy. MATERIALS AND METHODS: It was a retrospective review of data of patients that underwent open simple retropubic prostatectomy with technical modification of the trigone bladder neck complex in two Nigerian tertiary hospitals, by a single surgeon, from January 2007 to December 2011. The data analysed included the demographic variables, the modes of presentation, need for blood transfusion, duration of catheterization and the duration of hospital stay. The primary end-point was the development or otherwise of BNS. RESULTS: Eighty-seven patients' data were available for analysis from a total of 91 patients. The mean age (+/-standard deviation [SD]) was 65.14 years (+/-10.55). Preoperative urinary retention was present in 58% of the patients. The maximal flow rate (Qmax) was 12.05 ml/s among the 20 patients that had preoperative uroflowmetry. The transfusion rate was 35%, but almost two-third of them had only one unit of blood transfused. The mean weight (+/-SD) of the enucleated adenoma was 82.64 g (+/-36.63). Bladder irrigation was required in 14% of the patients, majority of the patients had urethral catheter removed after 96 h and the mean hospital stay was 6.52 days. No patient developed BNS after a mean follow-up duration of 16.39 months. CONCLUSION: Bladder neck stenosis can be a distressing complication of prostatectomy. The result of our technical modification of managing the trigone bladder-neck complex looks promising for prevention or delaying the onset of BNS. A long-term observation and a prospective randomised control trial to ascertain this initial experience is needed. PMID- 26834393 TI - Urinary stones in Eastern Saudi Arabia. AB - INTRODUCTION: Nephrolithiasis is a common problem worldwide especially in areas of the hot climate like Saudi Arabia. The aim of this analysis was to study the characteristics of urinary stones in Eastern Saudi Arabia and to report the following: Composition of urinary stones, age and gender distribution, seasonal variation of stone development, comorbid conditions associated with stone development and the incidence of urinary stones. METHODS: All urinary stones that were submitted to the Johns Hopkins Aramco Healthcare, previously Saudi Aramco Medical Services Organization for analysis from January 2011 through January 2013 were analyzed. RESULTS: A total of 384 urinary stones were collected and submitted for analysis from 347 patients. There was a male predominance with a male: female ratio of 3.9:1. The average age was 48.5 +/- 12.8 years. Weight abnormality was predominant in both genders, and especially females. Calcium based stones constituted the great majority (84.6%) followed by uric acid stones (12.8%). The other forms of stones were rare. More stones were recovered during the hot season, May to September. The calculated annual incidence of urolithiasis was 111/100,000 individuals. CONCLUSION: Calcium based stones are the most common urinary stones observed in Eastern Saudi Arabia. There is a clear association between the diagnosis of urinary stones and the hot season. PMID- 26834391 TI - Natural antimicrobial peptides as promising anti-HIV candidates. AB - Human immunodeficiency virus type 1 (HIV-1) infection remains to be one of the major global health problems. It is thus necessary to identify novel therapeutic molecules to combat HIV-1. Natural antimicrobial peptides (AMPs) have been recognized as promising templates for developing topical microbicides. This review systematically discusses over 80 anti-HIV peptides annotated in the antimicrobial peptide database (http://aps.unmc.edu/AP). Such peptides have been discovered from bacteria, plants, and animals. Examples include gramicidin and bacteriocins from bacteria, cyclotides from plants, melittins and cecropins from insects, piscidins from fish, ascaphins, caerins, dermaseptins, esculentins, and maximins from amphibians, and cathelicidins and defensins from vertebrates. These peptides appear to work by different mechanisms and could block viral entry in multiple ways. As additional advantages, such anti-HIV peptides may possess other desired features such as antibacterial, antiparasital, spermicidal, and anticancer activity. With continued optimization of peptide stability, production, formulation and delivery methods, it is anticipated that some of these compounds may eventually become new anti-HIV drugs. PMID- 26834395 TI - Mini percutaneous nephrolithotomy for renal calculi in paediatric patients: A review of twenty cases. AB - OBJECTIVE: The objective was to report our initial experience of mini percutaneous nephrolithotomy (mPCNL) performed on patients in the pediatric age group (<18 years) using a miniature nephroscope (12F). SUBJECTS AND METHODS: A total of 20 children underwent mPCNL for renal stone extraction in the Department of Urology, Yenepoya Medical College, Mangalore, India, from February 2013 to January 2014. The patients were evaluated on the basis of parameters viz. age at the time of surgery, size and number of stones, duration of surgery, stone clearance, and postoperative complications. RESULTS: A total of 20 mPCNLs were performed on children, with age ranging from 8 to 16 years. Three children had three stones each, six children had two stones each, eight children had one stone each, and three had multiple. The median stone burden was 1.36 cm. The procedure was via single puncture in 15 cases, and two punctures in five cases. Punctures were upper calyceal in seven cases, lower calyceal in seven cases, and combined upper and lower calyceal in six cases. The calculi were accessed by a 12F mini nephroscope, laser lithotripsy was used in 12 cases and pneumatic lithotripsy used for the rest. Total clearance was achieved in 18 out of 20 cases (90%). Postoperative complications developed in one child, in the form of sepsis. CONCLUSION: Our initial experience concludes that mPCNL is a safe and efficacious tool for the management of renal calculi in the pediatric population. PMID- 26834394 TI - Results of second transurethral resection for high-grade T1 bladder cancer. AB - BACKGROUND: The aim of this study was to examine the histological outcome and potential therapeutic benefit of second transurethral resection (TUR) for high grade T1 bladder cancer. PATIENTS AND METHODS: The subjects were 171 patients who underwent initial TUR between January 1993 and December 2013, and were diagnosed with high-grade T1 bladder cancer. Second TUR was performed within 4-6 weeks after the initial resection. Intravesical recurrence, invasive intravesical recurrence, and disease-free, progression-free, and overall survival were examined between second TUR group and no second TUR group. RESULTS: Of the 171 patients, 79 (46.2%) underwent second TUR. Histological findings from second TUR were no cancer in 33 (41.8%), carcinoma in situ in 18 (22.9%), Ta in 15 (19.0%), T1 in 12 (15.2%), and muscle invasive bladder cancer (T2) in 1 case (1.3%). The 5 and 10-year intravesical recurrence-free survival rates were 72.0% and 57.4%, respectively, and the disease-free survival rates at these times were 69.7% and 49.6%, respectively. Second TUR had no influence on intravesical recurrence, regardless of the use of Bacillus Calmette-Guerin (BCG) therapy. No BCG therapy and recurrent cancer were significantly associated with intravesical recurrence in multivariate analysis. Recurrent cancer was also a significant risk factor for invasive intravesical recurrence. BCG therapy significantly improved disease-free survival. Second TUR was a significant factor in overall survival. In the histological results for second TUR, no cancer and Tis cases had reduced intravesical recurrence compared to Ta and T1 cases. CONCLUSION: Second TUR allows more accurate staging and pT0 cases in second TUR have a better outcome, indicating a possible therapeutic benefit of the procedure. PMID- 26834396 TI - Does prostate volume affect the efficacy of alpha1D/A: Adrenoceptor antagonist naftopidil? AB - INTRODUCTION: There have been reports that one of the factors affecting the efficacy of alpha1-adrenoceptor antagonists (alpha1-blocker; alpha1-B) was prostate volume (PV). However, there are few reports of short-term prospective trials comparing the efficacy of alpha1-B by PV. We examined the influence of PV on the short-term efficacy of naftopidil dose increase therapy to administration of 75 mg/day after an initial dose of 50 mg/day. MATERIALS AND METHODS: A total of 85 patients with lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) received 50 mg/day of naftopidil for 4 weeks. After 4 weeks, the dosage of naftopidil was increased to 75 mg/day for a further 4 weeks. We divided the patients into two groups of PV >=40 mL at baseline (Group L) and PV <40 mL at baseline (Group S). RESULTS: International Prostate Symptom Score (IPSS), IPSS storage symptoms, and IPSS quality-of-life score were significantly improved at 4 and 8 weeks compared with baseline in both Groups. IPSS voiding symptoms (IPSS-VS) were significantly improved at 4 and 8 weeks compared with baseline in Group S. IPSS and IPSS-VS were significantly improved at 8 weeks compared with 4 weeks only in Group L. IPSS-VS and intermittency at 4 weeks were significantly decreased in Group S compared with Group L. Maximum flow rate was significantly improved at 8 weeks compared with baseline in Group L. CONCLUSIONS: PV is a predictive factor affecting the efficacy of naftopidil 50 mg/day for IPSS VS, and the dose increase to 75 mg/day effective for IPSS-VS. A total of 50 mg/day of naftopidil is the maintenance dose for LUTS/BPH patients with a small PV, and 75 mg/day of dose increase therapy should be chosen for patients with a large PV. PMID- 26834397 TI - Urologic complications following obstetrics and gynecologicai surgery: Our experience in a tertiary care hospital. AB - INTRODUCTION: Urinary tract injuries are a known complication of obstetrical and gynecological surgeries because of their anatomical proximity. Delayed diagnosis and improper management leads to high morbidity and even mortality. This is our three year's experience of urological complications after obstetric and gynecological surgery, their treatment and follows up. MATERIALS AND METHODS: We reviewed all cases of urological injuries managed in our department that were deemed to be of obstetric and gynecological origins. RESULTS: Thirty seven women were treated in the department for urological complications secondary to obstetric and gynecological procedures from January 2012 to December 2014. The most common organ involved was urinary bladder, occurring in 54% patients followed by ureter in 35.13%. Vesicovaginal fistula (VVF) was the most common injury involving the bladder occurring in nineteen patients. Ureterovaginal fistula (UVF) occurred in nine patients and acute ureteric injury in three. Hysterectomy was the most common etiology occurring in 60% cases followed by obstetrical causes in 40% cases. All cases were successfully managed both with open surgery or laparoscopic surgery. CONCLUSION: Although obstetrical causes are still important in developing countries, gynecological procedures especially laparoscopic surgeries are on the rise. In these procedures the suspicion of urological injuries should be kept in mind and intra-operative detection and early repair should be attempted. Delayed diagnosis and improper treatment leads to severe complications. PMID- 26834398 TI - Management of recurrent anterior urethral strictures following buccal mucosal graft-urethroplasty: A single center experience. AB - OBJECTIVE: To describe the safety, feasibility and outcome of redo buccal mucosal graft urethroplasty in patients presenting with recurrent anterior urethral stricture following previous failed BMG urethroplasty. MATERIALS AND METHODS: This was a retrospective chart review of 21 patients with recurrent anterior urethral stricture after buccal mucosal graft urethroplasty, who underwent redo urethroplasty at our institute between January 2008 to January 2014. All patients underwent preoperative evaluation in the form of uroflowmetry, RGU, sonourethrogram and urethroscopy. Among patients with isolated bulbar urethral stricture, who had previously undergone ventral onlay, redo dorsal onlay BMG urethroplasty was done and vice versa (9+8 patients). Three patients, who had previously undergone Kulkarni-Barbagli urethroplasty, underwent dorsal free graft urethroplasty by ventral sagittal urethrotomy approach. One patient who had previously undergone urethroplasty by ASOPA technique underwent 2-stage Bracka repair. Catheter removal was done on 21(st) postoperative day. Follow-up consisted of uroflow, PVR and AUA-SS. Failure was defined as requirement of any post operative procedure. RESULTS: Idiopathic urethral strictures constituted the predominant etiology. Eleven patients presented with stricture recurrence involving the entire grafted area, while the remaining 10 patients had fibrotic ring like strictures at the proximal/distal graft-urethral anastomotic sites. The success rate of redo surgery was 85.7% at a mean follow-up of 41.8 months (range: 1 yr-6 yrs). Among the 18 patients who required no intervention during the follow up period, the graft survival was longer compared to their initial time to failure. CONCLUSION: Redo buccal mucosal graft urethroplasty is safe and feasible with good intermediate term outcomes. PMID- 26834399 TI - Outcome of buccal mucosa and lingual mucosa graft urethroplasty in the management of urethral strictures: A comparative study. AB - OBJECTIVE: The objective of the study was to compare the outcome of buccal and lingual mucosa graft (LMG) augmentation urethroplasty along with donor sites morbidities in anterior urethra stricture. SUBJECTS AND METHODS: From September 2010 to January 2014, 125 patients underwent single stage augmentation urethroplasty. They were randomly divided into two groups to receive either buccal mucosa graft (BMG) or LMG. The patients were prospectively followed for complications and outcome. RESULTS: Baseline characteristics such as mean age, etiology, stricture length, and location were comparable in both groups. Overall success rate for Group 1 and Group 2 were 69.2% and 80%, respectively. Mean follow-up periods were 28.2 and 25 months in Group 1 and Group 2, respectively. CONCLUSIONS: LMG provides the better outcome with fewer immediate and delayed complications as compared to BMG. The length of stricture and width of graft were main factors affecting the outcome. PMID- 26834400 TI - Evaluating efficacy of various operative procedures done in anterior urethral stricture using urethral stricture score. AB - CONTEXT: Scoring systems have been an important tool of clinical decision making in medicine. As scoring systems like Glasgow Coma scale have made a revolutionary change in stratifying the patient, in particular, clinical scenario. Wiegand et al. in 2012 proposed UREThRAL Score a novel method to quantify anterior urethral stricture. AIMS: The aim was to validate urethral stricture score (USS) for evaluating the efficacy of operative procedures. SETTINGS AND DESIGN: Study was done in a retrospective manner and includes patients operated for anterior urethral stricture by a single surgeon in tertiary care center over the period of 2008-2014. SUBJECTS AND METHODS: A total of 57 cases were included in this study who met the inclusion criteria, of these cases 7 underwent excision and primary anastomosis (EPA), 20 underwent preputial flap urethroplasty (PFUP), 22 underwent tunica albuginea urethroplasty (TAU), and rest 8 underwent scrotal flap urethroplasty (SFUP). Procedures were assigned different complexity level, and USS was compared with the particular procedure to see the relation between both. STATISTICAL ANALYSIS USED: Data were analyzed using ANOVA on SPSS software. RESULTS: Mean USS for EPA, PFUP, TAU, and SFUP in our study group was found to be 6.57, 8.95, 9.00, and 10.00, respectively, with an overall USS of 9.03, with a standard deviation of 1.56. USS was significantly associated with complexity. CONCLUSIONS: Mean USS increased with increase in surgical complexity indicating that higher USS correlates with more complex surgery. Strongest association between complexity and the individual parameter was found with location and length. PMID- 26834401 TI - Outcome and erectile function following treatment of priapism: An institutional experience. AB - INTRODUCTION: Priapism has a devastating consequence on the sexual function of men if not promptly managed. We are presenting our experience of the treatment of priapism and the status of sexual function even following successful detumescence achieved after treatment. MATERIALS AND METHODS: Nineteen patients, who presented with priapism from January 2012 to December 2014, were included in the study. After obtaining a detailed history; color Doppler ultrasonography of penis and blood gas analysis of the initial corporal aspirate were done to ascertain the type of priapism. Standard protocol in our institute for management of priaprism was to start with conservative treatment by corporal aspiration and intracorporeal injection (ICI) of phenylephrine. On the failure of conservative management, distal shunts were performed. Proximal shunts were performed on the failure of distal shunt procedures. Erectile function was evaluated with International Index of Erectile Function-5 questionnaire on admission and during follow-up. RESULTS: All the patients had ischemic type priapism. Age of the patients ranged from 22 to 55 years. Duration of priapism varied from 20 to 480 h (mean 96.7). Etiologies attributed were; over-the-counter sildenafil use, chlorpromazine, opium intake and intracorporeal papaverine injection, chronic myeloid leukemia, and idiopathic. Five patients had preserved erectile function during follow-up. Preservation of normal erectile function following aspiration and ICI, proximal and distal shunt procedures were 66.7%, 18.1% and 20%, respectively. CONCLUSION: Patients with late presentation and those patients requiring higher treatment modalities (e.g., proximal shunts) for achieving detumescence will subsequently have a poor erectile function. These patients should be counseled about the early penile prosthesis placement during initial surgical management. PMID- 26834402 TI - Ultrasound-guided percutaneous sclerotherapy of simple renal cysts with n-butyl cyanoacrylate and iodized oil mixture as an outpatient procedure. AB - OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of ultrasound guided percutaneous sclerotherapy of symptomatic simple renal cysts with n-butyl cyanoacrylate (NBCA) and iodized oil mixture as an outpatient single session procedure. MATERIALS AND METHODS: A total of ninety two patients with 100 symptomatic simple renal cysts (larger than 5 cm) were treated by ultrasound (US) guided percutaneous aspiration and injection of NBCA and iodized oil mixture. The patients (68 men and 24 women, mean age, 42.4 +/- 10.5 years) were treated with as out-patients. The volume of the treated cysts was calculated with periodic noncontrast enhanced CT examinations 3, 6 and 9, months after the procedure. The procedure was considered successful at follow-up CT when there was total ablation or greater than 80% reduction of size with resolution of symptoms, respectively. Failure was defined as less than 80% reduction and/or persistent symptoms. RESULTS: The sclerotherapy was technically successful in all patients. The diameter of the cysts ranged between 5.5 and 13.5 cm (mean, 8.8 +/- 1.4 cm), and 1.5 and 3.8 cm (mean, 2.1 +/- 0.4 cm) before and after sclerotherapy, respectively (P < 0.001). Average diameter reduction was 83.7% during the follow up period. The mean follow- up lasted 7.1 months (3-11 months). Flank pain resolved in 86 of 92 symptomatic patients (93.48%). In six patients, the symptoms decreased slightly. The procedure was successful in 98 of 100 cysts (98%), demonstrated by follow-up CT. The only two failed cyst was larger than 10 cm in diameter and don't required any further treatment. We did not observe any procedure related complications. CONCLUSION: Ultrasound guided percutaneous sclerotherapy with NBCA and iodized oil mixture for management of symptomatic simple renal cysts was found to be a real time, effective, safe, well tolerated, alternative and simple technique that can be carried out by urologists as an outpatient procedure. PMID- 26834403 TI - Bilateral single-session retrograde intra-renal surgery: A safe option for renal stones up to 1.5 cm. AB - INTRODUCTION: Assessment of treatment outcomes in patients undergoing bilateral single-session retrograde intra-renal surgery (RIRS) for bilateral renal stones up to 1.5 cm. MATERIALS AND METHODS: Retrospective analysis of 74 patients was done with bilateral renal calculi, who underwent bilateral single-session RIRS at our stone referral hospital from December 2011 to May 2014. The selection criteria for this intervention were patient's preference, failure of other treatments and stone up to 1.5 cm. Patients with creatinine more than 2, pyonephrosis sepsis, bilateral impacted pelviureteric junction calculi were excluded from study. All patients were evaluated with serum biochemistry, urinalysis, urine culture, plain radiography of kidney-ureter-bladder, intravenous urography, renal ultrasonography (USG) and/or computed tomography (CT). Follow-up evaluation included serum biochemistry and postoperative plain film and renal USG. The success rate was defined as patients who were stone-free or only had a residual fragment of less than 4 mm. CT was conducted only in patients with residual stones, which were present in seven patients. RESULTS: A total of 74 patients (50 male, 24 female) with a mean age 39.2 +/- 15.2 were included in the present study. The mean stone size was 11.7 +/- 2.4 mm. The stone free rates were 86.84% and 97.29% after the first and second procedures, respectively. In eight patients (10.8%), minor complications were observed, whereas no major complications were noted in the studied group. There was no significant difference in pre- and post-operative serum creatinine levels. CONCLUSION: In patients with bilateral renal stones up to 1.5 cm bilateral single session RIRS with flexible ureteroscope can be safely performed with low complication rate. PMID- 26834404 TI - Study of predictive factors affecting the prolonged urinary leakage after percutaneous nephrolithotomy. AB - OBJECTIVE: To evaluate the factors that may influence the prolonged urinary leakage following percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: A total of 936 consecutive patients underwent PCNL during the study period from April 2013 to December 2014 at our center, and data were recorded prospectively. Patients who required stage PCNL, chronic renal failure and diabetic patients, concurrent ureteric stone and patients in whom double-J stent was placed because of ureteropelvic injury, or pelvicalyceal extravasation were excluded from the study. After exclusion, 576 patients were included in the study. The predictive factors that may lead to prolonged urinary leakage after PCNL were broadly categorized into patient-related factors and procedure-related factors. Patients were divided into two groups: Group 1 (n = 32) - Required double-J stent placement due to prolonged urinary leakage (>48 h) after removal of the nephrostomy tube. Group 2 (n = 544) - Did not require double-J stent placement. RESULTS: Patient-related factors such as stone complexity, grade of hydronephrosis, renal parenchymal thickness in access line, and intra-parenchymal renal pelvis were most important factors for prolonged urinary leakage (P < 0.05, P < 0.05, P < 0.05, and P < 0.05, respectively), while procedure-related factors such as multiple punctures, surgeon's experience, and residual stones were most important factors for prolonged urinary leakage (P < 0.05, P < 0.05, and P < 0.05, respectively). CONCLUSION: In the present study, several factors appear to affect post-PCNL prolonged urinary leakage. We suggest that patients who are at increased risk of prolonged urinary leakage double-J stent should be placed at the end of PCNL procedure. PMID- 26834405 TI - Metal telescopic and Amplatz sheath dilation in nephrolithotomy. AB - INTRODUCTION: Comparison of Amplatz sheath percutaneous nephrolithotomy (Amplatz PCNL) and metal telescopic dilation PCNL (MTD PCNL) with respect to clinical outcomes and complications. MATERIALS AND METHODS: Single-institution retrospective chart review with 73 patients who underwent PCNL divided into two groups: Amplatz PCNL (n = 26) and MTD PCNL (n = 47). Efficacy (stone-free rate, residual stones, and surgical duration) and safety (transfusion rate and hemoglobin decrease) were evaluated. Complications were recorded and classified using the modified Clavien classification system. RESULTS: The two PCNL groups were similar regarding mean age, stone burden, side, stone location, and stone composition. There were no significant differences in surgery duration (101 +/- 28 vs. 98 +/- 30 min; P = 0.906), transfusion rate (3.9% vs. 4.3%; P = 0.382), and hemoglobin drop (0.9 +/- 0.9 vs. 1 +/- 0.7 g/dl; P = 0.424) for Amplatz and MTD PCNL, respectively. Stone-free rate (86% vs. 68%; P = 0.001) was significantly higher while residual fragments rate (37% vs. 60%; P = 0.001) was significantly lower in Amplatz PCNL compared to MTD PCNL. However, tube stay time (4.4 +/- 1.8 vs. 5.8 +/- 3.6 days; P = 0.005) and hospital time (8.6 +/- 2.6 vs. 9.7 +/- 5.5 days; P = 0.0001) were significantly longer in Amplatz PCNL compared to MTD PCNL. Clavien grading revealed a significantly higher rate of low-grade complications (I-III) for the MTD PCNL in comparison to Amplatz PCNL (10.6% vs. 3.9%, respectively; P = 0.011). There were no major complications and no tract dilation failure. CONCLUSION: The study demonstrates that Amplatz PCNL is a safe and effective procedure to remove large renal stones compared with MTD PCNL. PMID- 26834406 TI - Are we fearful of tubeless percutaneous nephrolithotomy? Assessing the need for tube drainage following percutaneous nephrolithotomy. AB - OBJECTIVE: The objective was to demonstrate that percutaneous nephrolithotomy (PCNL) can be safely performed with a tubeless or totally tubeless drainage technique. INTRODUCTION: Standard PCNL includes nephrostomy tube placement designed to drain the kidney and operative tract at the conclusion of the procedure. Modern technique trend is tubeless PCNL and totally tubeless PCNL, which are performed without standard nephrostomy drainage. We aim to reinforce current literature in demonstrating that PCNL can be safely performed using a tubeless technique. With compounded supportive data, we can help generate a trend toward a more cost-effective procedure with improved pain profiles and patient satisfaction, as previously shown with the tubeless technique. METHODS: Retrospective analysis of 165 patients who underwent PCNL treatment was performed. Of this group, 127 patients underwent traditional nephrostomy drainage following PCNL. A tubeless procedure was performed in the remaining 38 patients. Patient's postoperative stone size and burden as well as complication profiles were analyzed. Largest stone size and total stone burden was similar between the groups. RESULTS: Patient characteristics and demographic information were compared and no significant statistical difference was identified between the groups. Complication rates between the groups were compared and no statistical difference was noted. A total of 23 patients had at least one postoperative complication. CONCLUSION: Tubeless and totally tubeless PCNL demonstrates equivalent outcomes in the properly selected patient group when compared to PCNL performed with a nephrostomy tube. Although this is not the first study to demonstrate this, a large majority of urologists continue standard nephrostomy placement after PCNL. More studies are needed that demonstrate safety of this practice to shift the pendulum of care. Thus, tubeless and totally tubeless PCNL can be performed safely and effectively, which has previously been shown to improve cost, patient pain profiles, and length of hospitalization. PMID- 26834407 TI - Thulium laser enucleation of the prostate is a safe and a highly effective modality for the treatment of benign prostatic hyperplasia - Our experience of 236 patients. AB - CONTEXT: Thulium LASER is fast emerging as a safe and effective modality for benign prostatic hyperplasia (BPH). Still, compared to holmium laser transurethral enucleation of the prostate (HoLEP) the number of institutes all over the world using Thulium LASER are limited. This is our effort to bring the statistical facts about the safety and effectivity of Thulium LASER. AIMS: To study the efficacy of thulium laser enucleation of the prostate (ThuLEP). SETTINGS AND DESIGN: All patients in the stipulated period were documented for all parameters and were evaluated. The results were tabulated. SUBJECTS AND MATERIALS: (1) Two hundred and thirty-six patients with symptomatic BPH were treated with ThuLEP between March 2010 and September 2014 at our institute by a single surgeon. (2) The inclusion criteria were maximum urinary flow rate (Qmax) <15 ml/s, International Prostate Symptoms Score (IPSS) >15 or acute retention of urine with the failure of catheter trial or Acute retention of urine with prior history of severe bladder outlet obstruction. (3) Patients evaluated by: Digital rectal examination, uroflowmetry, IPSS, prostate-specific antigen (PSA), blood and urine routine tests, abdominal usage with trains rectal ultrasonography (TRUS), TRUS guided biopsies. STATISTICAL ANALYSIS USED: Not used. RESULTS: (1) ThuLEP was a highly effective procedure as compared to all other procedures like HOLEP, TURP in terms of catheterization time, hospital stay, and drop in hemoglobin (Hb). (2) Catheterization time: 25.22 h (224 patients within 24 h and 12 patients within 48 h). (3) Hospital stay: 24-36 h 218 patients (92.3%), 36-48 h 18 patients (7.6%). (4) Drop in Hb: 0.8 +/- 0.42 g/dl. (5) Average operative time: 56.91 min. CONCLUSIONS: Thulium LASER is a safe and highly effective LASER in terms of blood loss, speed of tissue resection, drop in serum PSA, and versatility of prostatic resection. PMID- 26834408 TI - Selective use of laparoscopy in nonpalpable undescended testes. AB - INTRODUCTION: Approximately, 20% of undescended testes (UDT) are nonpalpable. Surgical management of the nonpalpable testis comprises laparoscopy. The aim of this study was to determine if ultrasonography can be used as a preoperative tool to localize the nonpalpable inguinal testis, eliminating the need for laparoscopy. METHODS: We identified 46 patients diagnosed with nonpalpable UDT between 2007 and 2012 who underwent an inguino-scrotal ultrasound preoperatively. We analyzed correlations between radiological and surgical findings. RESULTS: A total of 46 patients (53 UDT), median age 14 months (quartile 1(st): 7; 3(rd): 80) were included. Ultrasound localized the testis as intracanalicular in 24/53 (45.2%), intraabdominal in 10/53 (18.8%), scrotal in 1/53 (1.8%), and could not localize 18/53 (33.9%) testes. In 35/53 (66%) testes, the ultrasound location correlated with the surgical findings (P < 0.001). Ultrasound detection showed 96% sensitivity and 56% specificity for intracanalicular testes. CONCLUSION: The use of preoperative ultrasound in this series was helpful in identifying the location of nonpalpable testes in children. In particular, the ultrasound finding of an intracanalicular testis may preclude the need for laparoscopy. PMID- 26834409 TI - Semi-rigid ureteroscopy: Proximal versus distal ureteral stones. AB - OBJECTIVE: To evaluate the safety and efficacy of semi-rigid ureteroscopy in proximal and distal ureteral stones, and to compare the operative and perioperative characteristics between the two stone groups. MATERIALS AND METHODS: We retrospectively reviewed the medical records of patients who underwent semi-rigid ureteroscopy for management of ureteral stones at the International Medical Center between June 2007 and September 2012. All stones were fragmented using Holmium: yttrium-aluminum-garnet (YAG) laser lithotripter. Stones located above the pelvic brim are considered proximal and below it are distal. RESULTS: One hundred and ninety-one patients were included. One hundred and three patients (54%) underwent ureteroscopy for proximal stones and 88 (46%) for distal stones. The stone size in the proximal group was 10 mm (+/-5.5) versus 8.6 mm (+/-5) in the distal group. The initial stone-free rate for proximal and distal calculi were 89-98.2%, respectively. The perioperative complication rate was higher in the proximal group 10% compared to the distal group which is 1.5% (P = 0.06). Both groups have the same average of hospital stay 1.2 days. CONCLUSION: Although there is a clinical difference between proximal and distal calculi groups in terms of complication and stone-free rates, this difference remained statistically insignificant (P = 0.06). Using a smaller caliber semi rigid ureteroscopy combined with Holmium-YAG laser can be carried out as a day care procedure and showed a slightly higher risk in patients with proximal ureteral calculi which should be explained to the patient. PMID- 26834410 TI - Laparoscopic-assisted mini percutaneous nephrolithotomy in the ectopic pelvic kidney: Outcomes with the laser dusting technique. AB - INTRODUCTION: The treatment of renal lithiasis has undergone a sea change with the advent of extracorporeal shock wave lithotripsy (ESWL) and endourological procedures such as percutaneous nephrolithotomy (PCNL), ureterorenoscopy and retrograde intrarenal surgery (RIRS). The presence of anatomical anomalies, such as ectopic pelvic kidney, imposes limitations to such therapeutic procedures. This study is aimed to find a simple and effective way to treat the stones in ectopic kidney. MATERIALS AND METHODS: From 2010 to 2014, nine patients underwent laparoscopic-assisted mini PCNL with Laser dusting for calculi in ectopic pelvic kidneys at our hospital. Retrograde pyelography was done to locate the kidney. Laparoscopy was performed and after mobilizing the bowel and peritoneum, the puncture was made in the kidney and using rigid mini nephroscope, and stones were dusted with Laser. RESULTS: The median interquartile range (IQR) stone size was 18 (6.5) mm. Median (IQR) duration of the procedure was 90 (40) min. The median (IQR) duration of postoperative hospital stay was 4 (2) days. The stone clearance in our series was 88.9%, with only one patient having a residual stone. No intra- or post-operative complications were encountered. CONCLUSION: Laparoscopy assisted mini PCNL with Laser dusting offers advantages in ectopic pelvic kidneys in achieving good stone clearance, especially in patients with a large stone burden or failed ESWL or RIRS. PMID- 26834411 TI - Urinothorax: Case report and systematic review of the literature. AB - Urinothorax, the presence of urine in the pleural space, is a rare cause of pleural effusion, usually associated with obstructive uropathy, or urinary trauma. We present the case of a 3 year-old boy and a systematic review of the literature of the 44 cases encountered. After resection of a Wilm's tumour in the right kidney our patient presented acute respiratory distress associated with radiographically confirmed pleural effusion. With the initial diagnosis of pneumonia or malignant pleural effusion, a closed thoracotomy was performed. The liquid obtained suggested urine, which was confirmed by the laboratory. Cystoscopy with retrograde pyelography detected a fistula on the posterior wall of the right kidney. The report of cases worldwide is low, probably due to its low incidence but also to underdiagnosis. Respiratory symptoms are not always present and urological symptoms usually predominate. Diagnosis requires a high degree of clinical suspicion and is confirmed by the main biochemical marker: The ratio >1.0 pleural fluid creatinine and creatinine serum. PMID- 26834412 TI - Inflammatory pseudotumor of the urinary bladder: A case series among more than 2,000 urinary bladder tumor cases. AB - "Inflammatory pseudotumor" (IPT) has infrequently been reported in the medical journals. A retrospective analysis was conducted among more than 2,000 bladder tumor cases from January 1999 to December 2012 looking for patients with IPT in the final diagnosis. Six patients were found with median tumor size of 3.5 cm (range: 3-8 cm); computed tomography and/or magnetic resonance imaging was used to diagnose the tumor. All patients had complete resection of the tumors. On a median follow-up of 6 years (range: 2-10 years), no recurrences for IPT have been observed in all patients. We concluded that IPT is a rare disease of the urinary bladder and should be regarded with a high degree of suspicion. Although an extensive workup may be needed for definite diagnosis, it is worth to avoid unnecessary chemoradiotherapy or radical surgeries. PMID- 26834413 TI - Preejaculatory illness syndrome: Two cases of a rare psychosomatic disorder. AB - Human ejaculation happens in the orgasmic phase of the human sexual response cycle. Among psychosomatic ejaculatory disorders that may happen before ejaculation, we present two cases of preejaculatory illness syndrome. The two cases shared common symptoms of sympathetic over activity, the sensation of impending death, and muscle atonia with subsequent failure to ejaculate. Depression, anxiety disorders, and family histories of psychiatric problems were noticed as risk factors. Medical conditions that may lead to panic attack type symptoms were eliminated before the final diagnosis. After the failure of empirical medications, symptoms became controlled with fluoxetine. Patients reported a recurrence of the symptoms on trying to stop the prescribed medication. On the last follow-up, they still take fluoxetine on a regular base with satisfactory sexual life. PMID- 26834414 TI - Sequential unusual site metastases in renal cell cancer: Saga of repeated tumor implantation and prolonged survival without systemic therapy. AB - Renal cell cancer (RCC) is known to produce metastasis to unusual sites both synchronously and metachronously several years after the primary treatment. We report a rare case of RCC with three different, sequential, and each time isolated rare site metastasis to ureteric stump, surgical site, and urinary bladder over a period of 6 years after radical nephrectomy. At each recurrence, metastasectomy was carried out and no systemic therapy was administered. Eleven years after radical nephrectomy and 5 years after last resection, the patient remains disease free. Multiple recurrences can occur in RCC and complete surgical resection results in disease free survival. PMID- 26834415 TI - Ectopic ureter draining into the uterus. AB - We report a rare case of a 13-year-old female child with a right-sided duplex system with the upper moiety draining into the uterus. Only one such case has been reported in scientific literature in English, of ectopic ureter draining into the uterus has been reported in literature. The patient was managed with laparoscopic end-to-side ureteroureterostomy into the normal ureter of the lower moiety. PMID- 26834416 TI - Primary urinary bladder mucosa associated lymphoid tissue type lymphoma presenting as a close mimic for genitourinary tuberculosis: Case report and review of literature. AB - Primary lymphoma of the urinary bladder is a rare entity. It has a distinctively different presentation than the urothelial carcinoma, which is the most common form of bladder cancer, but might mimic inflammatory lesions such as tubercular cystitis, clinically as well as radiologically. We present a case of primary extranodal marginal zone lymphoma of the bladder, which was a close mimicker of tuberculosis, leading to delay in diagnosis. We highlight the role of biopsy in prompt diagnosis of these cases. We emphasize on the high index of suspicion required to identify such cases at an early stage, which has pronounced prognostic implications. PMID- 26834417 TI - Emphysematous pyelonephritis in failed renal allograft: Case report and review of literature. AB - Emphysematous pyelonephritis (EPN) in renal allograft is rare but potentially lethal complication and requires aggressive medical and/or surgical therapy to achieve cure. We report a case of 60-year-old diabetic male with poor cardiac function on maintenance hemodialysis, who underwent delayed allograft nephrectomy for EPN in failed renal allograft. Blood culture grew Bacteroides. He was stable in the postoperative period but passed away on day 4 due to myocardial infarction likely secondary to poor baseline cardiac function. Delay in diagnosis and treatment could have contributed to this unfavorable outcome. There is a paucity of published literature regarding EPN in the transplant population, such that management decisions (percutaneous conservative versus urgent surgical) are challenging. Further studies are required to establish treatment guidelines. PMID- 26834418 TI - Peritoneal seeding following incomplete resection of mixed epithelial stromal tumor of the kidney: First case report. AB - Mixed epithelial stromal tumor (MEST) is rare and typically benign renal cystic neoplasm that cannot be clinically distinguished from cystic renal cell carcinoma. Its mainstay course of diagnosis and treatment remains surgical excision. Recurrence and malignant transformation is rare but has previously been described. To our best knowledge, we present the first case of peritoneal seeding resulting in a paracolonic MEST following incomplete resection in a patient with benign MEST. This signifies a new pathological behavior for MEST, predominantly, a benign kidney tumor. In addition, documentation with more cases of MEST is needed to further understand its pathogenesis, clinical behavior, malignant potential, and optimal management. PMID- 26834420 TI - Ready for the next leap. PMID- 26834419 TI - Homocysteinemia: A rare cause of priapism. AB - Priaprism is a persistent painful erection that continuous beyond or is unrelated to sexual stimulation. Majority of cases are idiopathic (46%), alcohol and drug related (21%), perineal trauma (12%), sickle cell anemia and hypercoagualable state related (11%). We report case of priapism caused by hyperhomocysteinemia with favorable outcome with only few cases so far reported in the literature to the best of our knowledge. A 31 year-old male referred to our institution with non resolving priaprism for the last 6 days. Immediate distal shunt (Al-ghorab) was created but it could not achieve the detumescence. The penile Doppler showed no flow into the corpora, so a proximal shunt (Quackels) was made which achieved satisfactory detumescence. On thorough evaluation for the cause of priaprism, only homocysteine level was found to be significantly raised (40.46 umol/L), being the unusual and rare cause for priaprism. The patient was discharged on homocheck. In the follow-up the patient is on vacuum assisted device for the erectile dysfunction and has been advised for the penile implant. Priaprism being a urological emergency should be thoroughly evaluated even for the rare causes and should be timely intervened to avoid the unavoidable consequences of permanent erectile dysfunction. PMID- 26834421 TI - Efficacy and safety of a polyherbal formulation in hemorrhoids. AB - BACKGROUND: The medical management of hemorrhoids should include an integrated approach. This integrated approach can be achieved by polyherbal formulations containing anti-inflammatory, styptics, analgesics, and laxative effect which reduce inflammation, pain, and bleeding, and increase gastro-intestinal motility and soften stools. One such polyherbal kit is "ArshkeytTM, a 7 day kit," which consists of oral tablets and powder along with topical cream. OBJECTIVE: Efficacy and safety of ArshkeytTM, a 7 day kit, a marketed polyherbal formulation was evaluated in comparison with conventional therapy practiced in surgery outpatient departments. MATERIALS AND METHODS: Patients (n = 90) with hemorrhoids were randomly allocated to receive either ArshkeytTM or standard therapy (combination of oral Isabgul powder and 2% lidocaine gel) for 14 days. Assessment on the basis of rectal symptoms and proctoscopic examination was done on day 0, 7, and 14 to derive a "composite score" which ranged from 0 to 25 by a blinded evaluator. The primary endpoint was number of patients achieving composite score 0 at the end of therapy (day 14). Inter-group analysis was done using Chi-square test. RESULTS: On day 14, the composite score of 0 was achieved in 15 patients of ArshkeytTM group versus 6 patients receiving standard therapy. The symptoms and signs which showed significant improvement in ArshkeytTM group compared to standard treatment group were the tenesmus (visual analog score) score (P = 0.047), anal sphincter spasm (P = 0.0495) and a decrease in the grade of hemorrhoids (P = 0.0205) on day 14. ArshkeytTM was also more beneficial in case of bleeding hemorrhoids as compared to nonbleeding hemorrhoids (P < 0.05). The incidence of adverse drug reactions in both groups was comparable and no patient required any treatment for the same. CONCLUSION: "ArshkeytTM, a 7 day kit," was effective in the treatment of hemorrhoids and had a good safety profile. PMID- 26834422 TI - Exploring Bhavana samskara using Tinospora cordifolia and Phyllanthus emblica combination for learning and memory in mice. AB - BACKGROUND: Current medications for dementia and enhancement of learning and memory are limited hence we need to explore traditional medicinal systems like Ayurveda to investigate agents that can improve learning and enhance memory. OBJECTIVE: The present study was carried out to evaluate effects and mechanisms of Ayurveda drug formulations, Tinospora cordifolia (Tc) and Phyllanthus emblica (Pe) with and without Bhavana samskara on learning and memory of mice. MATERIALS AND METHODS: After approval of Animal Ethics Committee, Swiss albino mice were divided into seven groups, administered orally: Distilled water, Rivastigmine (2.4 mg/kg), Tc (100 mg/kg), Pe (300 mg/kg), 1 formulation (Tc + Pe: 400 mg/kg) and formulation 2 (Tc + Pe + Ocimum sanctum: 400 mg/kg) daily for 15 days. Piracetam (200 mg/kg) was injected daily intraperitoneally for 8 days. The mice underwent a learning session using elevated plus maze. Memory was tested 24 hours later. RESULTS: Mice pretreated with all the drugs showed a trend toward reducing transfer latencies but values were comparable to vehicle control. In all drug treated groups, a significant reduction in transfer latency was observed after 24 h. Improvement in learning and memory by both formulations were comparable to individual plant drugs, Tc and Pe. CONCLUSION: The plant drugs showed improvements in learning and memory. The fixed-dose formulations with Bhavana samskara, showed encouraging results as compared to individual agents but the difference was not statistically significant. Hence, the concept of Bhavana samskara could not be explored in the present study. However, these drugs showed comparable or better effects than the modern medicinal agents thus, their therapeutic potential as nootropics needs to be explored further. PMID- 26834423 TI - Wound healing and antimicrobial activity of two classical formulations of Laghupanchamula in rats. AB - BACKGROUND: Wounds affect a large number of patients and seriously reduce the quality of life. The wound as a medical problem was first discussed by Maharshi Agnivesha in Agnivesha Samhita (later known as Charaka Samhita) as Vrana. Laghupanchamula denotes a combination of the roots of five herbs. However, in Ayurvedic classics, besides four common herbs viz. Kantakari, Brihati, Shalaparni and Prinshniparni, the fifth one is either Gokshura (LPG) or Eranda (LPE), and both formulations have been documented to have wound healing (Vrana) activity. OBJECTIVE: The present study was undertaken to determine the in vivo wound healing activity and in vitro antimicrobial activity of 50% ethanolic extract of Laghupanchamula containing Gokshura (LPGE) and Laghupanchamula containing Eranda (LPEE) in rats with acute toxicity in mice. MATERIALS AND METHODS: LPGE and LPEE (1000 mg/kg) was administered orally, once daily for 10 days (incision wound model) or for 24 days (excision wound model) in rats. LPGE and LPEE was studied for its in vitro antimicrobial and in vivo wound breaking strength (WBS) (incision model) and rate of contraction, period of epithelization and histology of skin (excision model). RESULTS AND CONCLUSION: LPGE and LPEE showed antimicrobial activity against skin pathogens, enhanced WBS, rate of contraction, skin collagen tissue formation and early epithelization period with low scar area indicating enhanced healing with histological evidence of more collagen formation in skin tissues. LPGE and LPEE also showed anti-bacterial activity and seemed to be safe, and use of both formulations in Laghupanchamula for their wound healing and anti-microbial activities is thus authenticated. PMID- 26834424 TI - Role of chrysin on expression of insulin signaling molecules. AB - BACKGROUND: Currently available drugs are unsuccessful for the treatment of tye-2 diabetes due to their adverseside-effects. Hence, a search for novel drugs, especially ofplant origin, continues. Chrysin (5,7-dihydroxyflavone) is a flavonoid, natural component of traditional medicinal herbs, present in honey, propolis and many plant extracts that hasbeen used in traditional medicine around the world to treat numerous ailments. OBJECTIVE: The present study was aimed to identify the protective role of chrysin on the expression of insulin-signaling molecules in the skeletal muscle of high fat and sucrose-induced type-2 diabetic adult male rats. MATERIALS AND METHODS: The oral effective dose of chrysin (100 mg/kg body weight) was given once a day until the end of the study (30 days post induction of diabetes) to high fat diet-induced diabetic rats. At the end of the experimental period, fasting blood glucose, oral glucose tolerance, serum lipid profile, lipid peroxidation (LPO) and free radical generation, as well as the levels of insulin signaling molecules and tissue glycogen in the gastrocnemius muscle were assessed. RESULTS: Diabetic rats showed impaired glucose tolerance and impairment in insulin signaling molecules (IR, IRS-1, p-IRS-1Tyr(632), p- Akt(Thr308)), glucose transporter subtype 4 [GLUT4] proteins and glycogen concentration. Serum insulin, lipid profile, LPO and free radical generation were found to be increased in diabetic control rats. The treatment with chrysin normalized the altered levels of blood glucose, serum insulin, lipid profile, LPO and insulin signaling molecules as well as GLUT4 proteins. CONCLUSION: Our present findings indicate that chrysin improves glycemic control through activation of insulin signal transduction in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic male rats. PMID- 26834425 TI - Effect of Solanum surattense on mitochondrial enzymes in diabetic rats and in vitro glucose uptake activity in L6 myotubes. AB - BACKGROUND: S. surattense is widely used in Siddha medicine for various ailments. OBJECTIVE: The aim was to evaluate the impact of alcoholic leaf-extract of S. surattense on mitochondrial enzymes in streptozotocin (STZ) induced diabetic rats and to study the in vitro muscle glucose uptake activity on L6 myotubes. MATERIALS AND METHODS: The male albino Wistar rats were randomly divided into five groups of six animals each. Diabetes was induced by intraperitoneal injection of STZ (40 mg/kg body weight). After being confirmed the diabetic rats were treated with alcoholic leaf-extract of S. surattense (100 mg/kg body weight) for 45 days. The biochemical estimations (liver mitochondrial enzymes, antioxidants, thiobarbituric acid reactive substances [TBARS]) and histopathological studies were performed. Further, the in vitro muscle glucose uptake activity in L6 myotubes and messenger RNA (mRNA) expression of glucose transporter-4 (GLUT-4) was performed. RESULTS: In diabetic rats, the activities of liver mitochondrial enzymes were found to be significantly lowered. The mitochondrial TBARS level increased, whereas the activities/level of enzymatic and non-enzymatic antioxidants decreased in diabetic rats. Administration of S. surattense to diabetic rats significantly reversed the above parameters toward normalcy. Furthermore in diabetic rats, the histopathological studies showed growth of adipose tissue and shrinkage of islets in the pancreas, liver showed fatty change with mild inflammation of portal triad, and kidney showed messangial capillary proliferation of glomeruli and fatty infiltration of tubules. Treatment with S. surattense brought back these changes to near normalcy. The extract was analyzed for in vitro muscle glucose uptake activity in L6 myotubes and mRNA expression of GLUT-4 by semi-quantitative reverse transcriptase-polymerase chain reaction. One nano gram per millilitre of S. surattense leaf-extract gave 115% glucose uptake on L6 myotubes. It also showed elevated levels of GLUT-4 mRNA transcripts, when compared with control cells. CONCLUSION: These studies strongly support the anti-diabetic nature of S. surattense. PMID- 26834426 TI - Preparation and characterization of mercury-based traditional herbomineral formulation: Shwas kuthar rasa. AB - BACKGROUND: Shwas kuthar rasa is a prestigious and potential herbomineral formulation of Ayurveda tested on 100 years of time scale for the treatment of asthma, allergy, and other respiratory problems. However, there is a lack of scientific work on Shwas kuthar rasa. OBJECTIVE: To prepare and physicochemically evaluate mercury-based Shwas kuthar rasa herbomineral formulation of Ayurveda for asthma and allergy. MATERIALS AND METHODS: Shwas kuthar rasa was prepared as per Ayurvedic text and characterized by various modern analytical techniques, viz., transmission electron microscopy (TEM), X-ray diffraction (XRD), far infrared (IR) spectroscopy, fourier transform IR spectroscopy, energy dispersive X-ray analysis, and inductively coupled plasma-mass spectroscopy. RESULTS: Study clearly revealed that prepared Shwas kuthar rasa formulation shows several crystallites agglomerate into a single particle. It yields submicron size particle structure (1.22 MU) with TEM analysis. The usage of mercury in the formulation found in the form of mercuric sulfide (HgS) and reaching to nanocrystalline (31-56 nm) size by XRD analysis. CONCLUSION: The present study indicates Shwas kuthar rasa is nanocrystallite with submicron size particle. Trituration of Kajjali helps in the formation of HgS and increases the crystallinity in the formulation. PMID- 26834427 TI - Evaluation of the antidepressant activity of Moringa oleifera alone and in combination with fluoxetine. AB - BACKGROUND: The prevalence of mental depression has increased in recent years, and has become a serious health problem in most countries of the world, including India. Due to the high cost of antidepressant synthetic drugs and their accompanying side effects, the discovery of safer antidepressant herbal remedies is on the rise. Moringa oleifera (MO) (drumstick) has been used in traditional folk medicine, and in Ayurveda, it is considered as a valuable remedy for treating nervous system disorders as well as memory enhancing agent. OBJECTIVE: The present study was designed to evaluate the acute and chronic behavioral and antidepressant effects of alcoholic extracts of MO leaves in standardized mouse models of depression. MATERIALS AND METHODS: Alcoholic extracts of MO (MOE) leaves were prepared, and phytoconstituents were determined using appropriate chemical analytical methods. Following preliminary dose-finding toxicity studies, the biological activity of MOE was tested in Swiss albino mice. Animals were divided into six groups: Groups 1 and 2 served as vehicle control and fluoxetine (20 mg/kg) standard control, respectively. Groups 3 and 4 served as treatment groups and were orally administered ethanolic MOE at doses of 100 mg/kg and 200 mg/kg, respectively. Groups 5 and 6, respectively, received combination doses of MOE 100 mg/kg + 10 mg fluoxetine, and MOE 200 mg/kg + 10 mg/kg fluoxetine. Following acute and 14 days chronic treatments, all animals were tested using behavioral models of depression, such as forced swim test (FST), tail suspension test (TST), and locomotor activity test (LAT). RESULTS: Significant changes in all tested activities (FST, TST, LAT) of chronically dosed mice were observed, especially in animals given simultaneously combined doses of 200 mg/kg/day MOE + 10 mg/kg/day fluoxetine for 14 days. The antidepressant effect of MOE may have been invoked through the noradrenergic-serotonergic neurotransmission pathway, which is the hallmark of selective serotonin reuptake inhibitors (SSRI) class of drugs. CONCLUSION: The results obtained in this study suggest that combined administration of MOE with low doses of fluoxetine or other SSRI drugs seems to have promising potential. PMID- 26834428 TI - Dosha brain-types: A neural model of individual differences. AB - This paper explores brain patterns associated with the three categories of regulatory principles of the body, mind, and behavior in Ayurveda, called Vata, Pitta, and Kapha dosha. A growing body of research has reported patterns of blood chemistry, genetic expression, physiological states, and chronic diseases associated with each dosha type. Since metabolic and growth factors are controlled by the nervous system, each dosha type should be associated with patterns of functioning of six major areas of the nervous system: The prefrontal cortex, the reticular activating system, the autonomic nervous system, the enteric nervous system, the limbic system, and the hypothalamus. For instance, the prefrontal cortex, which includes the anterior cingulate, ventral medial, and the dorsal lateral cortices, would exhibit a high range of functioning in the Vata brain-type leading to the possibility of being easily overstimulated. The Vata brain-type performs activity quickly. Learns quickly and forgets quickly. Their fast mind gives them an edge in creative problem solving. The Pitta brain type reacts strongly to all challenges leading to purposeful and resolute actions. They never give up and are very dynamic and goal oriented. The Kapha brain-type is slow and steady leading to methodical thinking and action. They prefer routine and needs stimulation to get going. A model of dosha brain-types could provide a physiological foundation to understand individual differences. This model could help individualize treatment modalities to address different mental and physical dysfunctions. It also could explain differences in behavior seen in clinical as well as in normal populations. PMID- 26834429 TI - Weighted mean: A possible method to express overall Dhatu Sarata. AB - Several questions are being raised regarding the accuracy of the methods of diagnosis and reporting of various clinical parameters according to Ayurveda in recent times. Uniformity in reporting, issues related to inter-rater variability, uniformity in applying statistical tests, reliability, consistency, and validation of various tools, - are some of the major concerns that are being voiced. Dhatu Sarata is one such domain where no substantial work has been carried out to address these issues. The Sanskrit term "Dhatu" roughly translates as a "tissue." Sarata stands for the status of Dhatu in a given individual, i.e., it describes whether the status is excellent, moderate, or poor. In the available research literature, there are several gaps while dealing with and reporting the clinical assessment of Dhatu. Most of the workers group an individual into any one of the categories of Dhatu Sarata, and this approach neglects the contribution of other Dhatus to the overall Sarata in that individual. In this communication, we propose the usefulness of "weighted mean" in expressing the overall Sarata in an individual. This gives the researcher a freedom of not classifying an individual into any one group of Sarata, while also simultaneously allowing him/her to retain the focus on the status of an individual Dhatu. PMID- 26834430 TI - Pharmaceutical standardization of Apamarga kshara. AB - Standardization of herbal drugs is essential to certify their quality and purity. Kshara (alkaline substance) of Apamarga (Achyranthes aspera Linn.) is an important constituent in many Ayurvedic formulations, but its standard manufacturing process (SMP) is not attempted till date. This study is aimed to establish SMP for Apamarga kshara. In pharmaceutical process; generally the sediments of ash obtained at the end of washes will be discarded. However, in the study, we attempted to wash the sediments repeatedly by adding water to extract more Kshara. Apamarga was collected from the local area and authenticated. Kshara was prepared by following standard methods and the preliminary physicochemical profile was developed. It is observed that the ash yields Kshara even in the consecutive washes. First wash yielded 21.23% w/w Kshara, while the second and third washes yielded 9.38% w/w and 4.76% w/w, respectively. Repeated washes yield more Kshara. Hence, it is advocated to wash the ashes repeatedly. As the findings are encouraging, similar experiments can be extended to all other Kshara preparations. PMID- 26834431 TI - Effect of electro-acupuncture, massage, mud, and sauna therapies in patient with rheumatoid arthritis. AB - A 48-year-old married woman diagnosed with rheumatoid arthritis (RA) in 2007, came to our hospital in July 2014 with the complaint of severe pain and swelling over multiple joints, especially over small joints, which was associated with stiffness (more in morning), deformities of fingers and toes, with disturbed sleep and poor quality of life (QOL) for the past 7 years. She received a combination of electro acupuncture (14 sessions), massage (18 sessions), mud (18 sessions), and sauna (3 sessions) (EMMS) therapies for 30-min, 45-min, 30-min, and 15-min per session, respectively for 3 weeks. During and postintervention assessment showed reduction in visual analog scale score for pain, Depression Anxiety and Stress Scales and the Pittsburgh Sleep Quality Index scores. It also showed an increase in the scores of 10-Meter Walk Test, isometric hand-grip test, and short form-36 version-2 health survey. This result suggest that, the EMMS therapy might be considered as an effective treatments in reducing pain, depression, anxiety, and stress with improvement in physical functions, quality of sleep and QOL in patient with RA. EMMS therapies were tolerated and no side effects were reported by the patient. Though the results are encouraging, further studies are required with larger sample size and advanced inflammatory markers. PMID- 26834432 TI - Analysis of Virechana karma with Danti avaleha: A retrospective study. AB - Virechana (therapeutic purgation) is a common procedure that is widely practiced among the panchakarma treatments (pentad treatments). Various Virechaka dravyas (purgative drugs) have been described for Virechana. Even after critical analysis of Virechaka dravyas in the literature, still there is difficulty in the fixation of dose. Hence, the retrospective analysis of varied outcomes of Virechana with Danti (Baliospermum montanum) avaleha (linctus) is discussed in this paper. The study included twenty-seven case reports of patients who were administered Virechana with Danti avaleha. These case reports are of patients suffering from various ailments such as irregular menstrual cycles, polycystic ovarian syndrome, primary and secondary infertility, and psoriasis. Danti avaleha was administered at dose of 10 g and 5 g in the Krura (~strong) and Madhyama (~moderate/normal) Koshta (~GI tract) patients, respectively. Among seven Krura koshta patients, three of them resulted with Pravara (excellent) Shuddhi and other four resulted with Madhyama (medium) Shuddhi. In twenty Madhyama koshta patients, sixteen of them resulted with avara (minimum) Shuddhi and remaining four patients resulted with Madhyama shuddhi. Complications like Udara shoola (spasmodic pain of abdomen) and Vamana (emesis) were observed during Virechana. Majority of the patients suffered with Udara shoola were of Madhyama koshta. Vamana was seen in both Krura and Madhyama koshta patients. Irrespective of the type of Shuddhi and complications, all the patients resulted with Samyak Kaphaantiki Virikta lakshana (signs of perfect purgation with end expulsion of Kapha). The study concluded that the Krura koshta patients were tolerable for dose of 10 g and are expected to attain Pravara Shuddhi. Whereas Madhyama koshta patients were intolerable even to mild dose of 5 g, producing Avara shuddhi. PMID- 26834434 TI - Kayla's Story Is Our Story. AB - As a Lamaze Certified Childbirth Educator, I find myself reading a lot of posts on various birth-related Facebook groups. It's important for me to know the issues women are talking about, asking about, and concerned about. Late last year, I found myself drawn to the real-time labor of a woman in New Mexico who was desperately trying for a successful vaginal birth after cesarean. She was using the virtual Facebook group as her literal emotional support, and the reaction was unlike anything I have ever seen online before. Literally hundreds of women around the world were following her story and rallying behind her-a woman they had never met. This is Kayla's story, and it is our story. PMID- 26834433 TI - "YOGA FOR PROMOTION OF HEALTH": CONFERENCE HELD ON INTERNATIONAL DAY OF YOGA-2015 AT KOLAR. PMID- 26834435 TI - Executive Summary of Hormonal Physiology of Childbearing: Evidence and Implications for Women, Babies, and Maternity Care. AB - This report synthesizes evidence about innate hormonally mediated physiologic processes in women and fetuses/newborns during childbearing, and possible impacts of common maternity care practices and interventions on these processes, focusing on four hormone systems that are consequential for childbearing. Core hormonal physiology principles reveal profound interconnections between mothers and babies, among hormone systems, and from pregnancy through to the postpartum and newborn periods. Overall, consistent and coherent evidence from physiologic understandings and human and animal studies finds that the innate hormonal physiology of childbearing has significant benefits for mothers and babies. Such hormonally-mediated benefits may extend into the future through optimization of breastfeeding and maternal-infant attachment. A growing body of research finds that common maternity care interventions may disturb hormonal processes, reduce their benefits, and create new challenges. Developmental and epigenetic effects are biologically plausible but poorly studied. The perspective of hormonal physiology adds new considerations for benefit-harm assessments in maternity care, and suggests new research priorities, including consistently measuring crucial hormonally mediated outcomes that are frequently overlooked. Current understanding suggests that safely avoiding unneeded maternity care interventions would be wise, as supported by the Precautionary Principle. Promoting, supporting, and protecting physiologic childbearing, as far as safely possible in each situation, is a low-technology health and wellness approach to the care of childbearing women and their fetuses/newborns that is applicable in almost all maternity care settings. PMID- 26834436 TI - A Childbirth Educator's Commentary on Hormonal Physiology of Childbearing: Evidence and Implications for Women, Babies, and Maternity Care. AB - Sarah Buckley's game-changing report, Hormonal Physiology of Childbearing: Evidence and Implications for Women, Babies, and Maternity Care, provides the evidence that supporting, promoting, and protecting the normal physiology of childbirth produces the best outcomes for mothers and babies. In this article, a childbirth educator recommends key points from Buckley's report that should be included in Lamaze childbirth education classes. PMID- 26834437 TI - Pump Early, Pump Often: A Continuous Quality Improvement Project. AB - Research demonstrates that although many mothers initiate pumping for their critically ill children, few women are successful at maintaining milk supply throughout their infants' entire hospital stay. At the Garbose Family Special Delivery Unit (SDU) at the Children's Hospital of Philadelphia, we care for mothers who have critically ill infants born with complex cardiac and congenital anomalies. Human milk is viewed as a medical intervention at our institution. Therefore, nurses on the SDU wanted to ensure best practice in terms of pumping initiation. This article describes a continuous quality improvement project that ensured mothers pumped early and often. Childbirth educators can play a key role in preparing mothers who are anticipating an infant who will require hospitalization immediately post-birth. PMID- 26834438 TI - Dysregulated Breastfeeding Behaviors in Children Later Diagnosed With Autism. AB - Newborn breastfeeding behaviors have not been characterized in children later diagnosed with autism spectrum disorder (ASD). In a qualitative interview, 16 mothers (28-56 years) of children with ASD described their 19 full-term infants' (38-42 weeks' gestational age) breastfeeding behaviors. Nine mothers described their infants as demonstrating a dysregulated breastfeeding pattern of sucking without stopping of their own volition. The infants' latch, weight gain, and other behaviors were recalled as not problematic. This feature of dysregulated feeding pattern in infancy has not been reported previously for children with ASD. If supported by future research, the pattern of a dysregulated feeding pattern in newborns could be evaluated by clinicians in the general pediatric population and/or at-risk infant siblings of children with ASD. PMID- 26834439 TI - Australian Fathers' Study: What Influences Paternal Engagement With Antenatal Care? AB - This mixed-methods study explores factors associated with and levels of engagement of fathers in antenatal care. One hundred expectant fathers were recruited from antenatal clinics and community settings in Western Australia. They completed validated questionnaires. Eighty-three percent of expectant fathers reported a lack of engagement with antenatal care. Factors significantly associated with lack of engagement in multivariate analysis were working more than 40 hours a week and lack of adequate consultation by antenatal care staff. In qualitative analysis, 6 themes emerged in association with a lack of engagement. They were role in decision making, time pressures, the observer effect, lack of knowledge, barriers to attendance, and feeling unprepared or anxious. Care providers should involve fathers in consultations to improve paternal engagement. PMID- 26834440 TI - Shared Decision Making for Routine Infant Circumcision: A Pilot Study. AB - It is important that expectant parents receive accurate information about the benefits and risks of circumcision as well as the benefits and risks of having an intact foreskin when making a decision about routine infant circumcision (RIC). A pilot study was conducted using the shared decision making (SDM) conceptual model to guide expectant parents through a 3-phase decision-making program about RIC as part of their childbirth education class. The participants showed a high level of preparedness following each of the 3 phases. Preparedness score were highest for those who decided to keep their expected sons' penises natural. This SDM program was an effective way of guiding expectant parents through the decision-making process for RIC. PMID- 26834441 TI - The Birth of Miriam Hazel. AB - My birth story for Miriam Hazel starts well before her birth, with the birth of her sister, our first-born daughter Colbie Laia. When I gave birth to our first daughter 3 years prior, I was in a completely different place with my body and my mind. Birth was scary, recovery was rough, and my first year followed suit. During my pregnancy with Miriam Hazel, my obstetrician encouraged me to consider a natural birth. I talked to other women and although still frightened, I became more confident and had the birth I never knew I wanted. The birth of Miriam Hazel was incredible and the recovery was completely different. This is my story of Miriam Hazel's birth. PMID- 26834442 TI - Epidurals: Do They or Don't They Increase Cesareans? AB - The controversy over whether epidurals increase the risk of cesarean has raged since the 1970s. This article provides a history of of the early observational research designed to answer this question and an in-depth analysis of the most recent randomized control trials. Based on the research, the author concludes that we cannot assure women that epidurals do not increase the risk of cesarean. PMID- 26834443 TI - Results of a Needs Assessment to Guide the Development of a Website to Enhance Emotional Wellness and Healthy Behaviors During Pregnancy. AB - In preparation for developing a website to enhance emotional wellness and healthy lifestyle during the perinatal period, this study examined women's informational needs and barriers. Seventy-four women who were pregnant or had given birth completed an online survey inquiring about information needs and preferred sources related to psychosocial aspects and lifestyle behaviors. Information related to healthy diet choices and weight management, followed by exercise, was rated highly as a need. Information related to depression, stress, and anxiety was also rated as important. Health-care providers and the Internet were found to be preferred sources of information. Evidence-based websites can serve as a powerful low-cost educational resource to support and reinforce the health promotion advice received from their health-care providers. PMID- 26834444 TI - Depressive Symptoms and Violence Exposure: Contributors to Repeat Pregnancies Among Adolescents. AB - Depressive symptoms and violence exposure (VE) often cooccur and have been recognized to influence childbearing; contribution to repeat pregnancy is unclear and examined in this article. This cross-sectional, descriptive, study screened for depressive symptoms and VE among 193 adolescent mothers at a large county hospital in Southwestern United States. Repeat pregnancy and depressive symptoms characterized one-third and one-quarter of adolescents, respectively. Despite minimal disclosure of VE, repeat pregnancy was significantly influenced by child abuse and past traumatic life experiences. Assessments and interventions with adolescents should focus on frequency of repeat pregnancies and symptoms of depression and VE. Nurses and childbirth educators are poised to offer birth control information and education, support, and resources highlighting depression and VE to adolescents. PMID- 26834445 TI - The Roadmap to Breastfeeding Success: Teaching Child Development to Extend Breastfeeding Duration. AB - Although medical literature establishes the benefits of, recommendations for, and variables impacting breastfeeding duration, the belief that her baby is not satisfied causes many women to abandon breastfeeding. Infant behaviors commonly misinterpreted as breastfeeding problems include increased crying, hard to calm, difficult to wake up, "restless" sleeping, frequent awakenings at night, or seemingly inattentive to or uninterested in his or her mother. The Roadmap to Breastfeeding Success is an evidence-based, clinical project that integrates best practices in lactation support with child development theory. Using family friendly concepts and language, The Roadmap to Breastfeeding Success gives childbirth, lactation, and early parenting professionals background information and innovative resources to help mothers meet their breastfeeding goals, thus promoting the health and well-being of mothers, babies, families, and communities. PMID- 26834446 TI - Exploring Fathers' Role in Breastfeeding Practices in the Urban and Semiurban Settings of Karachi, Pakistan. AB - This study explored fathers' perceptions about breastfeeding infants. A qualitative exploratory study design was used. Study setting was urban and semiurban areas of Karachi, Pakistan. In-depth interviews were conducted with 12 fathers. The following themes emerged from the data collected: knowledge and awareness and enabling and impeding factors. Most fathers seemed eager to get involved and assist their partners in proper breastfeeding practices because they believed that doing so is in accordance with their faith. Fathers felt that adequate support from their family members and employers could enable them to encourage their partners to initiate and maintain exclusive and optimum breastfeeding practices. Exploring fathers' perception regarding breastfeeding in the context of Pakistan is still a new field of study. PMID- 26834447 TI - Good for the Self: Self-Compassion and Other Self-Related Constructs in Relation to Symptoms of Anxiety and Depression in Non-clinical Youths. AB - This study examined relationships among self-compassion, self-esteem, and self efficacy and symptoms of anxiety disorders and depression in a sample of 132 non clinical adolescents aged 12-17 years. The results first of all indicated that the Shortened Self-Compassion Scale for Adolescents was reliable (i.e., all Cronbach's alphas were >.70) and valid in terms of both construct (as demonstrated by a principal components analysis which revealed the hypothesized three-factor structure) and concurrent validity (i.e., as shown by means of positive correlations with self-esteem and self-efficacy). Further, the expected negative correlations were found between self-compassion and anxiety and depression, indicating that higher levels of this self-related construct are associated with lower symptom levels, and vice versa. Of the three components of self-compassion, mindfulness appeared most convincingly related to symptoms of anxiety and depression. Finally, when controlling for other self-related constructs, self-compassion no longer accounted for a significant proportion in the variance of symptom levels. In contrast, self-esteem (depression) and in particular self-efficacy (anxiety and depression) did show unique explanatory power. PMID- 26834448 TI - Willingness to use ADHD Self-Management: Mixed Methods Study of Perceptions by Adolescents and Parents. AB - Little is known about perceptions surrounding self-management for attention deficit hyperactivity disorder (ADHD), although such interventions appear commonly used and are considered essential components of the chronic care model. Our research is part of a mixed methods study that followed students at high and low risk for ADHD over 11 years. During the final study years, area representative samples of 148 adolescents (54.8% participation; 97 ADHD high-risk group; 51 low-risk peers) and 161 parents (59.4% participation; 108 parents of high-risk adolescent; 53 parents of low-risk peer) completed a cross-sectional survey on community-identified self-management interventions for ADHD (activity outlets, sleep regulation, dietary restriction, homework help, family rules, and prayer). Respondents also answered open-ended questions addressing undesirable self-management effects, which were analyzed using grounded theory methods. High risk adolescents expressed significantly lower willingness towards all self management interventions than did adult respondents, except for increased activity outlets. They also reported lower receptivity towards sleep regulation and dietary restriction than did their low-risk peer group. No gender or race differences in self-management willingness were found, except for higher receptivity to prayer in African American respondents. Cost, perceived ineffectiveness, disruptions to routines, causation of interpersonal conflicts, and reduced future self-reliance were seen as potential undesirable effects. Findings suggest that activity-based ADHD interventions appear particularly acceptable across all demographic and risk groups, unlike sleep regulation and dietary approaches. Further research on self-care effectiveness is needed to incorporate adolescents' viewpoints about ADHD self-management, as interventions may be acceptable to adults, but resisted by adolescents. PMID- 26834449 TI - Using social impact borrowing to expand preschool through third grade programs in urban public schools. AB - Budget constraints and difficulty raising taxes limit school districts from expanding education programming even when research shows that additional expenditures would generate economic benefits that are greater than costs. Recently, coalitions of private investors, philanthropists, education practitioners, and government finance analysts have emerged to create opportunities to expand education services that promise high rates of social net benefits without raising taxes or reducing other expenditures. These collaborators have a strong interest in obtaining careful estimates of educational program effectiveness. We describe the use of social-impact borrowing to increase access to the Child-Parent Center preschool-through-third-grade intervention for at-risk students in the Chicago Public School District. The partners include the city, school district, investors, nonprofit organizations, and a university. The key to the feasibility of social-impact borrowing is the ability to document that early intervention can reduce the need for later special education services. With the help of private investors and nonprofit organizations, it is possible for public school districts to finance services with funds from private sources and use future cost savings to repay this debt. We discuss how social-impact borrowing is being used in Chicago and in Salt Lake County as the nation's first two instances of using pay-for-performance social impact borrowing to support early education. PMID- 26834450 TI - Using Simulations to Investigate the Longitudinal Stability of Alternative Schemes for Classifying and Identifying Children with Reading Disabilities. AB - The present study employed data simulation techniques to investigate the one-year stability of alternative classification schemes for identifying children with reading disabilities. Classification schemes investigated include low performance, unexpected low performance, dual-discrepancy, and a rudimentary form of constellation model of reading disabilities that included multiple criteria. Data from Spencer et al. (2014) were used to construct a growth model of reading development. The parameters estimated from this model were then used to construct three simulated datasets wherein the growth parameters were manipulated in one of three ways: A stable-growth pattern, a mastery learning pattern and a fan-spread pattern. Results indicated that overall the constellation model provided the most stable classifications across all conditions of the simulation, and that classification schemes were most stable in the fan-spread condition, and were the least stable under the mastery learning growth pattern. These results also demonstrate the utility of data simulations in reading research. PMID- 26834451 TI - Correlates of African American female adolescent offenders 3, 4 Methylenedioxymethamphetamine (MDMA or "Ecstasy") use and sexually transmitted infection morbidity. AB - The current study was designed to determine the extent to which self-reported ecstasy use in a population of juvenile adolescent detainees in a southern state is associated with high-risk health behaviors pertaining to sexually transmitted infection (STI) symptomology and past history of STI occurrence. Participants were 764 African American females extracted from an overall sample of 2,260 juvenile offenders housed at selected Youth Development Campuses in the state of Georgia. Significance tests were conducted using univariate logistic regressions to examine the independent associations of participant's self-reported ecstasy use and dichotomized HIV risk behavior correlates and history of having a prior STI before the most recent incarceration Participants who reported ecstasy use prior to incarceration were 1.7 (OR = 1.68, 95% CI = 0.78-3.64) and 1.8 times (OR = 1.87, 95% CI = 1.24-2.81) more likely respectively to indicate having had genital warts or chlamydia, and were more than 1.5 times (OR = 2.21, 95% CI = 0.83-5.44) and two times more likely to report having had gonorrhea or herpes, accordingly. Prevention programs for adolescent offender populations should develop interventions that target adolescents' substance use behavior as a function of STI risk taking as well as being culturally competent to deal specifically with these problem behaviors. PMID- 26834452 TI - Clinical characteristics and selection of treatment modality for patients with vitreomacular traction: real-world implementation of NICE guidance (TA297). AB - AIM: To investigate the qualitative aspects in patient selection and the quantitative impact of disease burden in real world treatment of vitreomacular traction (VMT) and implementation of the National Institute for Health and Care Excellence (NICE) guidance (TA297). METHODS: A monocentric, retrospective review of consecutive patients undergoing optical coherence tomography (OCT) imaging over a 3 month period. Patients with VMT in at least one eye were identified for further data collection on laterality, visual acuity, symptoms, presence of epiretinal membrane, macular hole and treatment selection. RESULTS: A total of 3472 patients underwent OCT imaging with a total of 6878 eyes scanned. Out of 87 patients, 74 patients had unilateral VMT (38 right, 36 left) and 13 patients had bilateral VMT. Eighteen patients with unilateral VMT satisfied NICE criteria of severe sight problems in the affected eye. Eight were managed for a coexisting pathology, one refused treatment, one patient did not attend, two closed spontaneously, and one received ocriplasmin prior to the study start date. Only two patients with unilateral VMT received ocriplasmin and three underwent vitrectomy. Those failing to meet NICE criteria for unilateral VMT were predominantly asymptomatic (n=49) or had coexisting ERM (n=5) or both (n=2). CONCLUSION: Ocriplasmin provides an alternative treatment for patients with symptomatic VMT. Our data shows that the majority of patients with VMT do not meet NICE TA297 primarily due to lack of symptoms. Those meeting NICE criteria, but not treated, tended to have coexisting macular pathology. Variation in patient selection due to subjective factors not outlined in NICE guidance suggests that real world outcomes of ocriplasmin therapy should be interpreted with caution. PMID- 26834453 TI - A retrospective study of the real-life utilization and effectiveness of ranibizumab therapy for neovascular age-related macular degeneration in the UK. AB - PURPOSE: AURA was an international, retrospective, observational study that monitored the real-life use and effectiveness of ranibizumab injections in patients with neovascular age-related macular degeneration (nAMD). This paper reports the findings from the UK. METHODS: Patients who started treatment with ranibizumab between January 1, 2009, and August 31, 2009, and had documented follow-up to the end of their treatment and/or monitoring or until August 31, 2011, were retrospectively monitored; the diagnosis and subsequent decision to treat was made by the patient's own physician. Assessments included the change in visual acuity (standardized letter count) during the first and second years after start of ranibizumab therapy and resource utilization. RESULTS: Four hundred and ten patients from 13 UK centers were analyzed. The mean (standard deviation [SD]) letter score at baseline was 55.0 (17.8). The mean (SD) change in visual acuity from baseline was +6.0 (15.4) letters at year 1 and +4.1 (16.9) at year 2. Most of the patients (86.6%) completed a 3-month loading phase; the visual improvements were numerically higher in these patients. Over 2 years, the mean (SD) number of clinic visits and injections was 18.4 (5.0) and 9.0 (4.7), respectively. Resource use and visual acuity gains were greater than those observed in the global population, which included other countries enrolled in AURA (Canada, France, Germany, Ireland, Italy, the Netherlands, and Venezuela). When patients were stratified according to severity of nAMD (based on letter count at baseline), the mean change in visual acuity score at years 1 and 2 was also higher for the UK than for the global population across all subgroups. CONCLUSION: Monitoring and treatment rates were high in the UK, resulting in better visual acuity outcomes compared with other included countries. This suggests that translation of clinical study outcomes into real-life settings is achievable, but at the expense of higher resource utilization than is currently the norm in most developed countries. PMID- 26834455 TI - Surgical video recording with a modified GoPro Hero 4 camera. AB - BACKGROUND: Surgical videography can provide analytical self-examination for the surgeon, teaching opportunities for trainees, and allow for surgical case presentations. This study examined if a modified GoPro Hero 4 camera with a 25 mm lens could prove to be a cost-effective method of surgical videography with enough detail for oculoplastic and strabismus surgery. METHOD: The stock lens mount and lens were removed from a GoPro Hero 4 camera, and was refitted with a Peau Productions SuperMount and 25 mm lens. The modified GoPro Hero 4 camera was then fixed to an overhead surgical light. RESULTS: Camera settings were set to 1080p video resolution. The 25 mm lens allowed for nine times the magnification as the GoPro stock lens. There was no noticeable video distortion. The entire cost was less than 600 USD. CONCLUSION: The adapted GoPro Hero 4 with a 25 mm lens allows for high-definition, cost-effective, portable video capture of oculoplastic and strabismus surgery. The 25 mm lens allows for detailed videography that can enhance surgical teaching and self-examination. PMID- 26834456 TI - Complications of selective laser trabeculoplasty: a review. AB - Selective laser trabeculoplasty is a laser treatment to treat glaucoma. It was initially indicated for open-angle glaucoma but has been proven to be efficacious for various types of glaucoma. This review article summarizes the few rare complications that can be seen with selective laser trabeculoplasty. It also makes recommendations on how to avoid these problems and how to treat patients when these rare complications arise. PMID- 26834454 TI - Optimal management of idiopathic macular holes. AB - This review evaluates the current surgical options for the management of idiopathic macular holes (IMHs), including vitrectomy, ocriplasmin (OCP), and expansile gas use, and discusses key background information to inform the choice of treatment. An evidence-based approach to selecting the best treatment option for the individual patient based on IMH characteristics and patient-specific factors is suggested. For holes without vitreomacular attachment (VMA), vitrectomy is the only option with three key surgical variables: whether to peel the inner limiting membrane (ILM), the type of tamponade agent to be used, and the requirement for postoperative face-down posturing. There is a general consensus that ILM peeling improves primary anatomical hole closure rate; however, in small holes (<250 um), it is uncertain whether peeling is always required. It has been increasingly recognized that long-acting gas and face-down positioning are not always necessary in patients with small- and medium-sized holes, but large (>400 um) and chronic holes (>1-year history) are usually treated with long-acting gas and posturing. Several studies on posturing and gas choice were carried out in combination with ILM peeling, which may also influence the gas and posturing requirement. Combined phacovitrectomy appears to offer more rapid visual recovery without affecting the long-term outcomes of vitrectomy for IMH. OCP is licensed for use in patients with small- or medium-sized holes and VMA. A greater success rate in using OCP has been reported in smaller holes, but further predictive factors for its success are needed to refine its use. It is important to counsel patients realistically regarding the rates of success with intravitreal OCP and its potential complications. Expansile gas can be considered as a further option in small holes with VMA; however, larger studies are required to provide guidance on its use. PMID- 26834457 TI - Preparation, characterization, and in vivo evaluation of intranasally administered liposomal formulation of donepezil. AB - The adequate amount of drug delivery to the brain in neurological patients is a major problem faced by the physicians. Recent studies suggested that intranasal administration of liposomal formulation may improve the drug delivery to the brain. In the present study, an attempt was made to study the brain bioavailability of commonly used anti-Alzheimer drug donepezil (DNP) liposomal formulation by intranasal route in rats. We adopted the thin layer hydration technique for the preparation of liposomes by using cholesterol, polyethylene glycol, and 1,2-distearyl-sn-glycero-3-phosphocholine (DSPC). The prepared liposomes were characterized by determining particle size, shape, surface morphology, zeta potential, encapsulation efficiency, and in vitro release of DNP. The pharmacokinetic parameters of liposomal DNP in plasma and brain of rats were determined following oral and nasal administration. The results of this study showed that the DNP liposomal formulation was stable with a consistent size (102 +/- 3.3 nm) and shape. The prepared liposomes showed high encapsulation efficiency (84.91% +/-3 .31%) and sustained-release behavior. The bioavailability of DNP in plasma and brain increased significantly (P<0.05) after administration of liposomal formulation by the intranasal route. Histopathological examination showed that the formulation was safe and free from toxicity. It can be concluded that the nasal administration of liposomal preparation may provide an efficient and reliable mode of drug delivery to the central nervous system. PMID- 26834458 TI - Quetiapine monotherapy in acute treatment of generalized anxiety disorder: a systematic review and meta-analysis of randomized controlled trials. AB - BACKGROUND: Some studies have indicated the efficacy of quetiapine in the treatment of generalized anxiety disorder (GAD). OBJECTIVE: The purpose of this study was to systematically review the efficacy, acceptability, and tolerability of quetiapine in adult patients with GAD. METHODS: The SCOPUS, MEDLINE, CINAHL, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched in April 2015. All randomized controlled trials (RCTs) of GAD were considered to be included in this meta-analysis. All RCTs of quetiapine in GAD patients providing endpoint outcomes relevant to severity of anxiety, response rate, remission rate, overall discontinuation rate, or discontinuation rate due to adverse events were included. The version reports from suitable clinical studies were explored, and the important data were extracted. Measurement for efficacy outcomes consisted of the mean-changed scores of the rating scales for anxiety, and response rate. RESULTS: A total of 2,248 randomized participants in three RCTs were included. The pooled mean-changed score of the quetiapine-treated group was greater than that of the placebo-treated group and comparable to selective serotonin reuptake inhibitors (SSRIs). Unfortunately, the response and the remission rates in only 50 and 150 mg/day of quetiapine-XR (extended-release) were better than those of the placebo. Their response and remission rates were comparable to SSRIs. The rates of pooled overall discontinuation and discontinuation due to adverse events of quetiapine-XR were greater than placebo. Only the overall discontinuation rate of quetiapine-XR at 50 and 150 mg/day and the discontinuation rate due to adverse events of quetiapine-XR at 50 mg/day were comparable to SSRIs. CONCLUSION: Based on this meta-analysis, quetiapine-XR is efficacious in the treatment of GAD in adult patients. Despite its low acceptability and tolerability, the use of 50-150 mg/day quetiapine-XR for adult GAD patients may be considered as an alternative treatment. Further well-defined studies should be conducted to warrant these outcomes. PMID- 26834459 TI - Liposomal flucytosine capped with gold nanoparticle formulations for improved ocular delivery. AB - Nanoliposomes have an organized architecture that provides versatile functions. In this study, liposomes were used as an ocular carrier for nanogold capped with flucytosine antifungal drug. Gold nanoparticles were used as a contrasting agent that provides tracking of the drug to the posterior segment of the eye for treating fungal intraocular endophthalmitis. The nanoliposomes were prepared with varying molar ratios of lecithin, cholesterol, Span 60, a positive charge inducer (stearylamine), and a negative charge inducer (dicetyl phosphate). Formulation F6 (phosphatidylcholine, cholesterol, Span 60, and stearylamine at a molar ratio of 1:1:1:0.15) demonstrated the highest extent of drug released, which reached 7.043 mg/h. It had a zeta potential value of 42.5+/-2.12 mV and an average particle size approaching 135.1+/-12.0 nm. The ocular penetration of the selected nanoliposomes was evaluated in vivo using a computed tomography imaging technique. It was found that F6 had both the highest intraocular penetration depth (10.22+/-0.11 mm) as measured by the computed tomography and the highest antifungal efficacy when evaluated in vivo using 32 infected rabbits' eyes. The results showed a strong correlation between the average intraocular penetration of the nanoparticles capped with flucytosine and the percentage of the eyes healed. After 4 weeks, all the infected eyes (n=8) were significantly healed (P<0.01) when treated with liposomal formulation F6. Overall, the nanoliposomes encapsulating flucytosine have been proven efficient in treating the infected rabbits' eyes, which proves the efficiency of the nanoliposomes in delivering both the drug and the contrasting agent to the posterior segment of the eye. PMID- 26834460 TI - Evidence of the gastroprotective and anti- Helicobacter pylori activities of beta mangostin isolated from Cratoxylum arborescens (vahl) blume. AB - PURPOSE: beta-Mangostin (BM) from Cratoxylum arborescens demonstrated various pharmacological activities such as anticancer and anti-inflammatory. In this study, we aimed to investigate its antiulcer activity against ethanol ulcer model in rats. MATERIALS AND METHODS: BM was isolated from C. arborescens. Gastric acid output, ulcer index, gross evaluation, mucus production, histological evaluation using hematoxylin and eosin and periodic acid-Schiff staining and immunohistochemical localization for heat shock protein 70 (HSP70) and Bax proteins were investigated. Possible involvement of reduced glutathione, lipid peroxidation, prostaglandin E2, antioxidant enzymes, superoxide dismutase and catalase enzymes, radical scavenging, nonprotein sulfhydryl compounds, and anti Helicobacter pylori were investigated. RESULTS: BM showed antisecretory activity against the pylorus ligature model. The pretreatment with BM protect gastric mucosa from ethanol damaging effect as seen by the improved gross and histological appearance. BM significantly reduced the ulcer area formation, the submucosal edema, and the leukocytes infiltration compared to the ulcer control. The compound showed intense periodic acid-Schiff staining to the gastric mucus layer and marked amount of alcian blue binding to free gastric mucus. BM significantly increased the gastric homogenate content of prostaglandin E2 glutathione, superoxide dismutase, catalase, and nonprotein sulfhydryl compounds. The compound inhibited the lipid peroxidation revealed by the reduced gastric content of malondialdehyde. Moreover, BM upregulate HSP70 expression and downregulate Bax expression. Furthermore, the compound showed interesting anti-H. pylori activity. CONCLUSION: Thus, it could be concluded that BM possesses gastroprotective activity, which could be attributed to the antisecretory, mucus production, antioxidant, HSP70, antiapoptotic, and anti-H. pylori mechanisms. PMID- 26834463 TI - Patient survey to identify reasons for non-adherence and elicitation of quality of life concepts associated with immunosuppressant therapy in kidney transplant recipients. AB - BACKGROUND: Renal transplantation (RT) is considered the treatment of choice for end-stage renal disease compared to dialysis, offering better health-related quality of life (HRQoL) and higher survival rates. However, immunosuppressants are essential for the long-term survival of kidney grafts and patients' non adherence to their medication leads to poor outcomes. Immunosuppressants can also significantly alter patients' HRQoL because of their side effects and the complex chronic medication regimen they represent. PURPOSE: To elicit key concepts related to adherence to immunosuppressant therapy (IT) and reasons for non adherence in terms of patient reported outcomes, side effects, and the impact of the medication on HRQoL in RT population, including patient preference of once daily over twice-daily immunosuppressive regimen. Results were used to develop an IT-specific conceptual framework and provide suggestions for improving patients' adherence to IT. MATERIALS AND METHODS: Interviews were conducted with three clinical experts to determine key concepts related to RT and immunosuppressants. Thirty-seven participants in four focus groups were asked to cite important concepts related to adherence and impact of IT on HRQoL and to rate them. Qualitative analysis was conducted to code participants' responses. RESULTS: Non adherence among participants where admitted was unintentional. The reason for this included forgetfulness, interference with lifestyle, being asleep at the time the medication should be taken, change in routine, and impact of side effects. Overall, participants reported that the evening dose was more problematic to remember and that the exclusion of this dose could make them more adherent. Participants also reported that IT impacted on their HRQoL in a number of ways including: placing restrictions on their lifestyle, causing anxiety, or impairing their ability to work. CONCLUSION: This study provides qualitative evidence about the barriers to IT adherence and the components of HRQoL that are important from the perspective of RT patients. The developed conceptual framework of IT-HRQoL in RT transplants, including social, psychological, and work life domains, can be used to inform the development of a new IT-specific measure of HRQoL in RT patients for use in head-to-head clinical trials or observational studies. Despite limitations associated with the number and the age range of patients recruited, this study suggests that a change in the regimen from twice daily to once daily among other measures could improve their adherence to IT and their HRQoL by placing less restrictions on their lifestyles. PMID- 26834461 TI - YiQiFuMai powder injection ameliorates blood-brain barrier dysfunction and brain edema after focal cerebral ischemia-reperfusion injury in mice. AB - YiQiFuMai powder injection (YQFM) is a modern preparation derived from the traditional Chinese medicine Sheng-Mai-San. YQFM is widely used in clinical practice in the People's Republic of China, mainly for the treatment of microcirculatory disturbance-related diseases. However, little is known about its role in animals with ischemic stroke. The aim of this study was to examine the effect of YQFM on brain edema and blood-brain barrier (BBB) dysfunction induced by cerebral ischemia-reperfusion (I/R) injury. Male C57BL/6J mice underwent right middle cerebral artery occlusion for 1 hour with a subsequent 24-hour reperfusion to produce I/R injury. YQFM (three doses: 0.336, 0.671, and 1.342 g/kg) was then given intraperitoneally (IP). The results demonstrated that YQFM significantly decreased infarct size, improved neurological deficits, reduced brain water content, and increased cerebral blood flow after I/R injury. 18F fluorodeoxyglucose micro-positron emission tomography imaging and hematoxylin and eosin staining results indicated that YQFM is able to ameliorate brain metabolism and histopathological damage after I/R. Moreover, YQFM administration reduced BBB leakage and upregulated the expression of zona occludens-1 (ZO-1) and occludin, which was confirmed by Evans Blue extravasation, Western blotting, and immunofluorescence assay. Our findings suggest that YQFM provides protection against focal cerebral I/R injury in mice, possibly by improving BBB dysfunction via upregulation of the expression of tight junction proteins. PMID- 26834462 TI - Clinical pharmacology study of cariprazine (MP-214) in patients with schizophrenia (12-week treatment). AB - PURPOSE: Cariprazine is a potent dopamine D3-preferring D3/D2 receptor partial agonist in development for the treatment of schizophrenia, bipolar mania, and depression. Pharmacokinetics of cariprazine and the two clinically relevant metabolites (desmethyl- and didesmethyl-cariprazine) was evaluated in a clinical pharmacology study. METHODS: This was a multicenter, randomized, open-label, parallel-group, fixed-dose (3, 6, or 9 mg/day) study of 28-week duration (<=4 week observation, 12-week open-label treatment, and 12-week follow-up). Once daily cariprazine was administered to 38 adult patients with schizophrenia. The pharmacokinetics of cariprazine, metabolites, and total active moieties (sum of cariprazine and two metabolites) was evaluated; efficacy and safety were also assessed. RESULTS: Steady state was reached within 1-2 weeks for cariprazine and desmethyl-cariprazine, 4 weeks for didesmethyl-cariprazine, and 3 weeks for total active moieties. Cariprazine and desmethyl-cariprazine levels decreased >90% within 1 week after the last dose, didesmethyl-cariprazine decreased ~50% at 1 week, and total active moieties decreased ~90% within 4 weeks. Terminal half lives of cariprazine, desmethyl-cariprazine, and didesmethyl-cariprazine ranged from 31.6 to 68.4, 29.7 to 37.5, and 314 to 446 hours, respectively. Effective half-life (calculated from time to steady state) of total active moieties was ~1 week. Incidence of treatment-emergent adverse events was 97.4%; 15.8% of patients discontinued due to adverse events. No abnormal laboratory values or major differences from baseline in extrapyramidal symptoms were observed. CONCLUSION: Cariprazine and its active metabolites reached steady state within 4 weeks, and exposure was dose proportional over the range of 3-9 mg/day. Once-daily cariprazine was generally well tolerated in adult patients with schizophrenia. PMID- 26834464 TI - Factors associated with diet barriers in patients with poorly controlled type 2 diabetes. AB - BACKGROUND: The study was conducted to investigate the diet barriers perceived by patients with poorly controlled type 2 diabetes and examine the associations between diet barriers and sociodemographic characteristics, medical condition, and patient-centered variables. METHODS: Secondary subgroup analyses were conducted based on the responses of 246 adults with poorly controlled type 2 diabetes from a multicenter, cross-sectional study. Diet barriers were captured by the Diet Barriers subscale of the Personal Diabetes Questionnaire. Participants also completed validated measures of diet knowledge, empowerment level, and appraisal of diabetes. Multiple regression techniques were used for model building, with a hierarchical block design to determine the separate contribution of sociodemographic characteristics, medical condition, and patient centered variables to diet barriers. RESULTS: Diet barriers were moderately evident (2.23+/-0.86) among Chinese patients with poorly controlled type 2 diabetes. The feeling of deprivation as a result of complying with a diet was the most recognized diet barrier (3.24+/-1.98), followed by "eating away from home" (2.79+/-1.82). Significantly higher levels of diet barriers were observed among those with lower levels of diet knowledge (beta=-0.282, P<0.001) and empowerment (beta=-0.190, P=0.015), and more negative appraisal (beta=0.225, P=0.003). CONCLUSION: Culturally tailored, patient-centered intervention programs that acknowledge individuals' preferences and allow for flexibility in diet management should be launched. Interventions programs that could enhance diet knowledge, promote positive appraisal, and improve empowerment level might effectively address diet barriers perceived by patients with poorly controlled type 2 diabetes. PMID- 26834465 TI - The incidence of cervical spondylosis decreases with aging in the elderly, and increases with aging in the young and adult population: a hospital-based clinical analysis. AB - BACKGROUND AND PURPOSE: Cervical spondylosis is well accepted as a common degenerative change in the cervical spine. Compelling evidence has shown that the incidence of cervical spondylosis increases with age. However, the relationship between age and the incidence of cervical spondylosis remains obscure. It is essential to note the relationship between age and the incidence of cervical spondylosis through more and more clinical data. METHODS: In the case-controlled study reported here, retrospective clinical analysis of 1,276 cases of cervical spondylosis has been conducted. We analyzed the general clinical data, the relationship between age and the incidence of cervical spondylosis, and the relationship between age-related risk factors and the incidence of cervical spondylosis. A chi-square test was used to analyze the associations between different variables. Statistical significance was defined as a P-value of less than 0.05. RESULTS: The imaging examination demonstrated the most prominent characteristic features of cervical spondylosis: bulge or herniation at C3-C4, C4 C5, and C5-C6. The incidence of cervical spondylosis increased with aging before age 50 years and decreased with aging after age 50 years, especially in the elderly after 60 years old. The occurrence rate of bulge or herniation at C3-C4, C4-C5, C5-C6, and C6-C7 increased with aging before age 50 years and decreased with aging after age 50 years, especially after 60 years. Moreover, the incidence of hyperosteogeny and spinal stenosis increased with aging before age 60 years and decreased with aging after age 60 years, although there was no obvious change in calcification. The age-related risk factors, such as hypertension, hyperlipidemia, diabetes, cerebral infarct, cardiovascular diseases, smoking, and drinking, have no relationship with the incidence of cervical spondylosis. CONCLUSION: A decreasing proportion of cervical spondylosis with aging occurs in the elderly, while the proportion of cervical spondylosis increases with aging in the young and the adults. This investigation implicates that aging is not only a contributor to the clinical performance of cervical spondylosis in the elderly, although the incidence of cervical spondylosis is proportional to the progress of age. PMID- 26834467 TI - Factors contributing to quality of life in COPD patients in South Korea. AB - OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease, and the burden of COPD is expected to increase in the rapidly aging nation of South Korea. This study aims to examine the factors contributing to health-related quality of life (HRQOL) in COPD patients. PATIENTS AND METHODS: This study was based on 6-year-data obtained from the Korean National Health and Nutrition Examination Survey 2007-2012. COPD was diagnosed in 2,734 survey participants and the severity was graded according to the criteria set by the Global Initiative for Chronic Obstructive Lung Disease. The EuroQol-5D (EQ-5D) index was used to assess the quality of life. RESULTS: The EQ-5D index scores for COPD patients and the general population were 0.915+/-0.003 and 0.943+/-0.001, respectively. Males, younger people, and patients with higher education attainment and income levels had a higher utility score. In addition, the adjusted EQ-5D index scores for severity level IV significantly decreased by 0.100 (P=0.041), compared to the severity group I scores. No significant differences were found in stage II and III patients. Comorbidities (excluding cancer and hypertension) appeared to negatively influence HRQOL among COPD patients. In particular, depression (EQ-5D index score =-0.089, P=0.0003) and osteoporosis (EQ-5D index score=-0.062, P=0.0039) had a significant influence, while smoking status did not appear to influence patient HRQOL. CONCLUSION: In this study, we found that the higher the severity of COPD, the lower the quality of life. In particular, patients with depression and osteoporosis had a relatively low utility score. Therefore, these comorbidities should be carefully monitored in order to improve quality of life. PMID- 26834466 TI - Characteristics of reversible and nonreversible COPD and asthma and COPD overlap syndrome patients: an analysis of salbutamol Easyhaler data. AB - The choice of inhaler device for bronchodilator reversibility is crucial since suboptimal inhalation technique may influence the result. On the other hand, bronchodilator response also varies from time to time and may depend on patient characteristics. In this study, patients with airway obstruction (forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio <70% in chronic obstructive pulmonary disease [COPD]; <80% in asthma) were included (n=121, age: 57.8+/-17.3 years). Bronchodilator reversibility (American Thoracic Society/European Respiratory Society criteria) was tested in patients with COPD (n=63) and asthma and COPD overlap syndrome (ACOS; n=12). Forty-six asthmatics served as controls. Reversibility was tested with 400 ug salbutamol dry powder inhaler (Buventol Easyhaler, Orion Pharma Ltd, Espoo, Finland). Demographic data and patients' perceptions of Easyhaler compared with beta2-agonist pressurized metered dose inhalers (pMDIs) were analyzed. American Thoracic Society/European Respiratory Society guideline defined reversibility was found in 21 out of 63 COPD patients and in two out of 12 ACOS patients. Airway obstruction was more severe in COPD patients as compared with controls (mean FEV1 and FEV1% predicted both P<0.0001). Average response to salbutamol was significantly lower in COPD patients compared with asthma controls (P<0.0001). Reversibility was equally often found in smokers as in never-smokers (33% vs 34%). Nonreversible COPD patients had higher mean weight, body mass index, and FEV1/FVC compared with reversible COPD patients. Most patients preferred Easyhaler and defined its use as simpler and more effective than use of a pMDI. Never-smokers and patients with asthma experienced Easy-haler somewhat easier to use than smokers and patients with COPD. In conclusion, a substantial part of patients with COPD or ACOS showed reversibility to salbutamol dry powder inhaler. Nonreversible patients with COPD were characterized by higher weight and body mass index, and a higher FEV1/FVC ratio. Most patients preferred Easyhaler compared with a pMDI. PMID- 26834468 TI - COPD exacerbations associated with the modified Medical Research Council scale and COPD assessment test among Humana Medicare members. AB - BACKGROUND: The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC) or COPD assessment test (CAT) score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs. METHODS: The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (>=2 encounters with International Classification of Dis eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, >=30 days apart). The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs. RESULTS: Among a total of 1,159 members who returned the survey, a 66% (765) completion rate was observed. Mean (standard deviation) age among survey completers was 72.0 (8.3), 53.7% female and 91.2% white. Odds ratios for having post-index exacerbations were 3.06, 4.55, and 16.28 times for members with 1, 2, and >=3 pre-index exacerbations, respectively, relative to members with 0 pre-index exacerbations (P<0.001 for all). The odds ratio for high vs low symptoms using CAT was 2.51 (P<0.001). Similarly, exacerbation-related costs were 73% higher with each incremental pre-index exacerbation, and over four fold higher for high-vs low-symptom patients using CAT (each P<0.001). The symptoms using mMRC were not statistically significant in either model (P>0.10). CONCLUSION: The patient-reported symptoms contribute important information related to future COPD exacerbations and exacerbation related costs beyond that explained by exacerbation history. PMID- 26834469 TI - UV photofunctionalization promotes nano-biomimetic apatite deposition on titanium. AB - BACKGROUND: Although biomimetic apatite coating is a promising way to provide titanium with osteoconductivity, the efficiency and quality of deposition is often poor. Most titanium implants have microscale surface morphology, and an addition of nanoscale features while preserving the micromorphology may provide further biological benefit. Here, we examined the effect of ultraviolet (UV) light treatment of titanium, or photofunctionalization, on the efficacy of biomimetic apatite deposition on titanium and its biological capability. METHODS AND RESULTS: Micro-roughed titanium disks were prepared by acid-etching with sulfuric acid. Micro-roughened disks with or without photofunctionalization (20 minute exposure to UV light) were immersed in simulated body fluid (SBF) for 1 or 5 days. Photofunctionalized titanium disks were superhydrophilic and did not form surface air bubbles when immersed in SBF, whereas non-photofunctionalized disks were hydrophobic and largely covered with air bubbles during immersion. An apatite-related signal was observed by X-ray diffraction on photofunctionalized titanium after 1 day of SBF immersion, which was equivalent to the one observed after 5 days of immersion of control titanium. Scanning electron microscopy revealed nodular apatite deposition in the valleys and at the inclines of micro roughened structures without affecting the existing micro-configuration. Micro roughened titanium and apatite-deposited titanium surfaces had similar roughness values. The attachment, spreading, settling, proliferation, and alkaline phosphate activity of bone marrow-derived osteoblasts were promoted on apatite coated titanium with photofunctionalization. CONCLUSION: UV photofunctionalization of titanium enabled faster deposition of nanoscale biomimetic apatite, resulting in the improved biological capability compared to the similarly prepared apatite-deposited titanium without photofunctionalization. Photofunctionalization-assisted biomimetic apatite deposition may be a novel method to effectively enhance micro-roughened titanium surfaces without altering their microscale morphology. PMID- 26834470 TI - Preparation, characterization, and in ovo vaccination of dextran-spermine nanoparticle DNA vaccine coexpressing the fusion and hemagglutinin genes against Newcastle disease. AB - Plasmid DNA (pDNA)-based vaccines have emerged as effective subunit vaccines against viral and bacterial pathogens. In this study, a DNA vaccine, namely plasmid internal ribosome entry site-HN/F, was applied in ovo against Newcastle disease (ND). Vaccination was carried out using the DNA vaccine alone or as a mixture of the pDNA and dextran-spermine (D-SPM), a nanoparticle used for pDNA delivery. The results showed that in ovo vaccination with 40 MUg pDNA/egg alone induced high levels of antibody titer (P<0.05) in specific pathogen-free (SPF) chickens at 3 and 4 weeks postvaccination compared to 2 weeks postvaccination. Hemagglutination inhibition (HI) titer was not significantly different between groups injected with 40 MUg pDNA + 64 MUg D-SPM and 40 MUg pDNA at 4 weeks postvaccination (P>0.05). Higher antibody titer was observed in the group immunized with 40 MUg pDNA/egg at 4 weeks postvaccination. The findings also showed that vaccination with 40 MUg pDNA/egg alone was able to confer protection against Newcastle disease virus strain NDIBS002 in two out of seven SPF chickens. Although the chickens produced antibody titers 3 weeks after in ovo vaccination, it was not sufficient to provide complete protection to the chickens from lethal viral challenge. In addition, vaccination with pDNA/D-SPM complex did not induce high antibody titer when compared with naked pDNA. Therefore, it was concluded that DNA vaccination with plasmid internal ribosome entry site-HN/F can be suitable for in ovo application against ND, whereas D-SPM is not recommended for in ovo gene delivery. PMID- 26834471 TI - Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate. AB - PURPOSE: The purpose of the present research was to develop a novel electrosprayed nanospherule providing the most optimized aqueous solubility and oral bioavailability for poorly water-soluble fenofibrate. METHODS: Numerous fenofibrate-loaded electrosprayed nanospherules were prepared with polyvinylpyrrolidone (PVP) and Labrafil((r)) M 2125 as carriers using the electrospray technique, and the effect of the carriers on drug solubility and solvation was assessed. The solid state characterization of an optimized formulation was conducted by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, and Fourier transform infrared spectroscopic analyses. Oral bioavailability in rats was also evaluated for the formulation of an optimized nanospherule in comparison with free drug and a conventional fenofibrate-loaded solid dispersion. RESULTS: All of the electrosprayed nanospherule formulations had remarkably enhanced aqueous solubility and dissolution compared with free drug. Moreover, Labrafil M 2125, a surfactant, had a positive influence on the solubility and dissolution of the drug in the electrosprayed nanospherule. Increases were observed as the PVP/drug ratio increased to 4:1, but higher ratios gave no significant increases. In particular, an electrosprayed nanospherule composed of fenofibrate, PVP, and Labrafil M 2125 at the weight ratio of 1:4:0.5 resulted in a particle size of <200 nm with the drug present in the amorphous state. It demonstrated the highest solubility (32.51+/-2.41 MUg/mL), an excellent dissolution (~85% in 10 minutes), and an oral bioavailability ~2.5-fold better than that of the free drug. It showed similar oral bioavailability compared to the conventional solid dispersion. CONCLUSION: Electrosprayed nanospherules, which provide improved solubility and bioavailability, are promising drug delivery tools for oral administration of poorly water-soluble fenofibrate. PMID- 26834472 TI - Quantitative detection of the tumor-associated antigen large external antigen in colorectal cancer tissues and cells using quantum dot probe. AB - The large external antigen (LEA) is a cell surface glycoprotein that has been proven to be highly expressed in colorectal cancer (CRC) as a tumor-associated antigen. To evaluate and validate the relationship between LEA expression and clinical characteristics of CRC with high efficiency, LEA expression levels were detected in 85 tissue blocks from CRC patients by quantum dot-based immunohistochemistry (QD-IHC) combined with imaging quantitative analysis using quantum dots with a 605 nm emission wavelength (QD605) conjugated to an ND-1 monoclonal antibody against LEA as a probe. Conventional IHC was performed in parallel for comparison. Both QD-IHC and conventional IHC showed that LEA was specifically expressed in CRC, but not in non-CRC tissues, and high LEA expression was significantly associated with a more advanced T-stage (P<0.05), indicating that LEA is likely to serve as a CRC prognostic marker. Compared with conventional IHC, receiver operating characteristic analysis revealed that QD-IHC possessed higher sensitivity, resulting in an increased positive detection rate of CRC, from 70.1% to 89.6%. In addition, a simpler operation, objective analysis of results, and excellent repeatability make QD-IHC an attractive alternative to conventional IHC in clinical practice. Furthermore, to explore whether the QD probes can be utilized to quantitatively detect living cells or single cells, quantum dot-based immunocytochemistry (QD-ICC) combined with imaging quantitative analysis was developed to evaluate LEA expression in several CRC cell lines. It was demonstrated that QD-ICC could also predict the correlation between LEA expression and the T-stage characteristics of the cell lines, which was confirmed by flow cytometry. The results of this study indicate that QD-ICC has the potential to noninvasively detect rare circulating tumor cells in clinical samples in real clinical applications. PMID- 26834473 TI - In vitro apoptotic and DNA damaging potential of nanobarium oxide. AB - Barium oxide nanoparticles (BaONPs) are an important industrial compound and are widely used in polymers and paints. In this study, apoptotic and genotoxic effects of BaONPs in mouse embryonic fibroblast (L929) cells were determined by using single-cell gel test. In vitro cytotoxicity assays were performed to assess BaONPs' toxicity in L929 cells. Mild cytotoxicity was observed in L929 cells due to BaONPs. BaONPs increased lipid peroxidation, catalase, and superoxide dismutase levels and lowered glutathione levels in L929 cells. This was accompanied by concomitant generation of reactive oxygen species and activation of caspase-3 in BaONPs-treated L929 cells. On the other hand, when we exposed L929 cells to BaONPs for 24 and 48 hours (comet assay), there was a duration- and dose-dependent increase in DNA impairment detected in the single-cell gel test. Thus, BaONPs exhibit genotoxic and apoptotic effects in L929 cells, most likely due to initiation of oxidative damage. PMID- 26834474 TI - Higher emotional intelligence is related to lower test anxiety among students. AB - BACKGROUND: For students attending university courses, experiencing test anxiety (TA) dramatically impairs cognitive performance and success at exams. Whereas TA is a specific case of social phobia, emotional intelligence (EI) is an umbrella term covering interpersonal and intrapersonal skills, along with positive stress management, adaptability, and mood. In the present study, we tested the hypothesis that higher EI and lower TA are associated. Further, sex differences were explored. METHOD: During an exam week, a total of 200 university students completed questionnaires covering sociodemographic information, TA, and EI. RESULTS: Higher scores on EI traits were associated with lower TA scores. Relative to male participants, female participants reported higher TA scores, but not EI scores. Intrapersonal and interpersonal skills and mood predicted low TA, while sex, stress management, and adaptability were excluded from the equation. CONCLUSION: The pattern of results suggests that efforts to improve intrapersonal and interpersonal skills, and mood might benefit students with high TA. Specifically, social commitment might counteract TA. PMID- 26834475 TI - Incidence and risk factors of postoperative delirium in elderly patients undergoing transurethral resection of prostate: a prospective cohort study. AB - AIM: The aim of the present study was to investigate the occurrence of postoperative delirium (POD) in elderly patients undergoing transurethral resection of prostate (TURP) and to identify those factors associated with delirium. METHODS: From July 2010 to February 2015, 358 patients, aged >=65 years and undergoing TURP were prospectively enrolled. Personal, medical and cognitive data, laboratory assessments, pain intensity, preoperative medications, and details of hemodynamic control were collected as predictors of delirium. POD was assessed using the Confusion Assessment Method. RESULTS: In the present study, POD occurred in 28 out of 358 cases (7.8%) after TURP, with duration of 1-4 days. The multivariate analysis showed that old age and visual analog scale pain scores were associated with POD. Marital status, body mass index, education, alcohol consumption, smoking history, preoperative psychotropic medication usage, activities of daily living scores, preoperative Mini-Mental Status Examination score, anesthesia type, American Society of Anesthesiologists classification, or hypotensive episodes during surgery did not significantly correlate with the occurrence of POD. CONCLUSION: Old age and pain intensity after surgery were found as the risk factors for the development of delirium in elderly patients undergoing TURP. These findings might help develop preventive strategies to decrease POD through targeted evaluation. PMID- 26834477 TI - Prevalence of multiple sclerosis in Al Quseir city, Red Sea Governorate, Egypt. AB - BACKGROUND: Multiple sclerosis (MS) is a chronic and disabling disorder with considerable social effects and economic sequelae. It is one of the major causes of disability in young adults. OBJECTIVES: This study aimed at detecting the prevalence of MS among the population of Al Quseir city. METHODS: This study is a part of door-to-door survey of major neurological disorders that was conducted in Al Quseir city, Red Sea Governorate, Egypt. The sample size was 33,285 persons. The youngest patient was 17 years old. The number of people at and above 17 years of age was 21,827. They were screened by three neurologists. Then, the positive cases were subjected to meticulous clinical evaluation by three staff members of Department of Neurology, Assiut University Hospital, Egypt. Essential investigations were done. RESULTS: A total of three cases of MS were diagnosed with an age-specific prevalence >=17 years of 13.7/100,000. PMID- 26834476 TI - Uncovering the etiology of conversion disorder: insights from functional neuroimaging. AB - Conversion disorder (CD) is a syndrome of neurological symptoms arising without organic cause, arguably in response to emotional stress, but the exact neural substrates of these symptoms and the underlying mechanisms remain poorly understood with the hunt for a biological basis afoot for centuries. In the past 15 years, novel insights have been gained with the advent of functional neuroimaging studies in patients suffering from CDs in both motor and nonmotor domains. This review summarizes recent functional neuroimaging studies including functional magnetic resonance imaging (fMRI), single photon emission computerized tomography (SPECT), and positron emission tomography (PET) to see whether they bring us closer to understanding the etiology of CD. Convergent functional neuroimaging findings suggest alterations in brain circuits that could point to different mechanisms for manifesting functional neurological symptoms, in contrast with feigning or healthy controls. Abnormalities in emotion processing and in emotion-motor processing suggest a diathesis, while differential reactions to certain stressors implicate a specific response to trauma. No comprehensive theory emerges from these clues, and all results remain preliminary, but functional neuroimaging has at least given grounds for hope that a model for CD may soon be found. PMID- 26834478 TI - Video-assisted thoracic surgery reduces early postoperative stress. A single institutional prospective randomized study. AB - BACKGROUND: Video-assisted thoracic surgery (VATS) has been shown to effectively reduce postoperative pain, enhance mobilization of the patients, shorten in hospital length of stay, and minimize postoperative morbidity rates. The aim of this prospective study is to evaluate neuroendocrine and respiratory parameters as stress markers in cancer patients who underwent lung wedge resections, using both mini muscle-sparing thoracotomy and VATS approach. METHODS: The patients were randomly allocated into two groups: Group A (n=30) involved patients who were operated on using the VATS approach, while in group B (n=30), the mini muscle-sparing thoracotomy approach was used. Neuroendocrine and biological variables assessed included blood glucose levels, C-reactive protein (CRP) levels, cortisol, epinephrine, and adrenocorticotropic hormone (ACTH) levels. Arterial oxygen (PaO2) and carbon dioxide (PaCO2) partial pressure were also evaluated. All parameters were measured at the following time points: 24 hours preoperatively (T1), 4 hours (T2), 24 hours (T3), 48 hours (T4), and 72 hours (T5), after the procedure. RESULTS: PaO2 levels were significantly higher 4 and 24 hours postoperatively in group A vs group B, respectively (T2: 94.3 vs 77.9 mmHg, P=0.015, T3: 96.4 vs 88.7 mmHg, P=0.034). Blood glucose (T2: 148 vs 163 mg/dL, P=0.045, T3: 133 vs 159 mg/dL, P=0.009) and CRP values (T2: 1.6 vs 2.5 mg/dL, P=0.024, T3: 1.5 vs 2.1 mg/dL, P=0.044) were found increased in both groups 4 and 24 hours after the procedure. However, their levels were significantly lower in the VATS group of patients. ACTH and cortisol values were elevated immediately after the operation and became normal after 48 hours in both groups, without significant difference. Postoperative epinephrine levels measured in group A vs group B, respectively, (T2: 78.9 vs 115.6 ng/L, P=0.007, T3: 83.4 vs 122.5 ng/L, P=0.012, T4: 67.4 vs 102.6 ng/L, P=0.021). The levels were significantly higher in group B. CONCLUSION: This study confirmed that minimally invasive thoracic surgery, by means of VATS, significantly reduces the acute phase response and surgical stress, while enables better postoperative oxygenation. PMID- 26834479 TI - Comparison of three approaches of Bernese periacetabular osteotomy. AB - BACKGROUND: Developmental dysplasia of the hip is a common disease and treated with various surgical approaches. Improved ilioinguinal (I-I) approach, two incision Smith-Peterson (TSP) approach, and modified Smith-Peterson (MSP) approach are three main approaches; however, they are rarely compared. The present study compared the operative time, blood loss, intraoperative and postoperative allogeneic blood transfusion, and postoperative complications of these three different approaches. HYPOTHESIS: Surgical approach does not influence the operation time, blood loss, and complications of periacetabular osteotomy. LEVEL OF EVIDENCE: Level III. Case-control study. PATIENTS AND METHODS: In a total of 101 hips of 95 cases, from February 2010 to July 2011, three different approaches of Bernese periacetabular osteotomy, I-I, TSP, and MSP, were conducted. The operation time, intraoperative bleeding, allogeneic blood transfusion, and early complications in different operation approaches were compared by a retrospective study when there were similar ages, genders, and lesions. RESULTS: Among the three approaches, I-I had less operation time and more blood loss (P<0.05), TSP had less blood loss (P<0.05) but more complications, and MSP had less blood loss (P<0.05) and less complications. DISCUSSION: The MSP approach is superior to the other two approaches in doing periacetabular osteotomy. PMID- 26834481 TI - The Saudi Arabia Food and Drug Authority: An Evaluation of the Registration Process and Good Review Practices in Saudi Arabia in Comparison with Australia, Canada and Singapore. AB - OBJECTIVE: This study compares the current regulatory review process and good review practices at the Saudi Food and Drug Authority (SFDA) with those of regulatory agencies in Australia, Canada, and Singapore and identifies opportunities for developing the SFDA as a Regional Centre of Excellence. METHODS: A questionnaire completed by the SFDA included data regarding the organisation, key milestones, review timelines, and good review practices of the agency. Similar information was obtained within the same timeframe (2014/2015) through the same standard questionnaire regarding the processes and practices for Health Canada, Singapore's Health Sciences Authority, and Australia's Therapeutic Goods Administration. RESULTS: All four regulatory agencies have established target times for scientific assessment and regulatory review, examine dossier sections in parallel, and separate company response time from overall timing. Additionally, all four agencies have instituted good review practices including standard operating procedures, templates, dossier monitoring, and continuous improvement processes, and assign a high priority to transparency in their relationships with the public, healthcare professionals and industry. Of the four agencies, however, only the SFDA requires a Certificate of Pharmaceutical Product (CPP) at the time of the submission and pricing negotiations before final product approval. CONCLUSIONS: To assist the SFDA in its efforts to become a Regional Centre of Excellence, it is suggested that the agency explore a risk stratification approach to select dossiers for verification, abridged, or full reviews; use forms of certification other than the CPP; make pricing negotiations independent to the review process; and introduce a feedback process for the quality of the dossier. PMID- 26834480 TI - The value of trabectedin in the treatment of soft tissue sarcoma. AB - Soft tissue sarcomas (STSs) are a group of rare tumors accounting for less than 1% of all adult malignant tumors, a heterogeneous group of more than 50 histological subtypes. Five percent to 30% of STS patients experience local recurrence and 10%-38% present with clinically detectable metastases. Doxorubicin either alone or in combination with ifosfamide has been used as first-line chemotherapy for advanced disease. After failure of first-line chemotherapy, high dose ifosfamide, gemcitabine + docetaxel, and dacarbazine may be applicable, although high-level evidence is lacking. Trabectedin is a synthetic, marine derived alkylating agent derived from the Caribbean tunicate, Ecteinascidia turbinata. Several clinical trials have shown that trabectedin has a favorable toxicity profile and is an alternative therapeutic option in adult patients with advanced STS who have not responded to treatment with doxorubicin and ifosfamide. Several clinical trials also recommend the 24-hour intravenous infusion every 3 weeks regimen. The most frequently reported grade 3/4 adverse events were neutropenia and elevated serum levels of AST/ALT. Steroid pretreatment is an effective way of reducing the extent of hepatotoxicity, and steroids are now given routinely before trabectedin administration. Further studies are ongoing to evaluate the efficacy and safety of combination therapy of trabectedin with other agents. PMID- 26834482 TI - Association between polymorphisms in selected inflammatory response genes and the risk of prostate cancer. AB - Inflammation represents an important event which facilitates prostate carcinogenesis. Genetic variations in inflammatory response genes could affect the level and function of the protein products, resulting in the differential prostate cancer risk among carriers of different variants. This study attempted to investigate the association of IL-4 rs2243250, IL-6 rs10499563, IL-8 rs4073, as well as NFKBIA rs2233406 and rs3138053 polymorphisms with prostate cancer risk in the Chinese population. Genotyping of the polymorphisms was performed by using polymerase chain reaction-restriction fragment length polymorphism technique on 439 prostate cancer patients and 524 controls, and the association of each polymorphic genotype with prostate cancer risk was evaluated by using logistic regression analysis based on allele, heterozygous, and homozygous comparison models, with adjustment to age and smoking status. We showed that the C allele of IL-4 rs2243250 polymorphism could increase prostate cancer risk (heterozygous comparison model: odds ratio [OR] =1.434, 95% confidence interval [CI] =1.092 1.881, P=0.009; homozygous comparison model: OR =2.301, 95% CI =1.402-3.775, P=0.001; allele comparison model: OR =1.509, 95% CI =1.228-1.853, P<0.001). On the other hand, the C allele of rs10499563 polymorphism could decrease prostate cancer risk (heterozygous comparison model: OR =0.694, 95% CI =0.525-0.918, P=0.010; homozygous comparison model: OR =0.499, 95% CI =0.269-0.926, P=0.028; allele comparison model: OR =0.692, 95% CI =0.553-0.867, P=0.001). No association was observed for the other polymorphisms. In conclusion, IL-4 rs2243250 and IL-6 rs10499563 polymorphisms could serve as potential predictive biomarkers for prostate cancer risk in the Chinese population. PMID- 26834483 TI - Silencing of Foxp3 delays the growth of murine melanomas and modifies the tumor immunosuppressive environment. AB - Forkhead box p3 (Foxp3) expression was believed to be specific for T-regulatory cells but has recently been described in non-hematopoietic cells from different tissue origins and in tumor cells from both epithelial and non-epithelial tissues. The aim of this study was to elucidate the role of Foxp3 in murine melanoma. The B16F10 cell line Foxp3 silenced with small interference Foxp3 plasmid transfection was established and named B16F10.1. These cells had lower levels of Foxp3 mRNA (quantitative real-time reverse transcription-polymerase chain reaction [0.235-fold]), protein (flow cytometry [0.02%]), CD25(+) expression (0.06%), cellular proliferation (trypan blue staining), and interleukin (IL)-2 production (enzyme-linked immunosorbent assay [72.35 pg/mL]) than those in B16F10 wild-type (WT) cells (P<0.05). Subcutaneous inoculation of the B16F10.1 cell line into C57BL/6 mice delayed the time of visible tumor appearance, increased the time of survival, and affected the weight of tumors, and also decreased the production of IL-10, IL-2, and transforming growth factor beta compared with mice inoculated with the B16F10 WT cell line. The B16F10.1 cells derived from tumors and free of T-cells (isolated by Dynabeads and plastic attachment) expressed relatively lower levels of Foxp3 and CD25(+) than B16F10 WT cells (P<0.05) in a time-dependent manner. The population of tumor-infiltrating lymphocytes of T CD4(+) cells (CD4(+), CD4(+)CD25(+), and CD4(+)CD25(+)Foxp3(+)) increased in a time-dependent manner (P<0.05) in tumors derived from B16F10 WT cells and decreased in tumors derived from B16F10.1 cells. Similar data were obtained from spleen cells. These results suggest that, in melanomas, Foxp3 partly induces tumor growth by modifying the immune system at the local and peripheral level, shifting the environment toward an immunosuppressive profile. Therapies incorporating this transcription factor could be strategies for cancer treatment. PMID- 26834484 TI - The synergistic anticancer effect of cisplatin combined with Oldenlandia diffusa in osteosarcoma MG-63 cell line in vitro. AB - BACKGROUND: Oldenlandia diffusa (OD) is a well-known traditional Chinese medicine, which is used to prevent and treat many disorders, especially cancers. However, its role in osteosarcoma has not been well understood. Here, we used OD and cisplatin individually and combined in osteosarcoma MG-63 cell to explore whether OD could induce cellular apoptosis and suppress the ability of proliferation and invasion of osteosarcoma MG-63 cell. METHODS: The changes of cellular shape were analyzed by optical microscopy. 3-(4,5-Dimethylthiazol-2-yl) 2,5-diphenyltetrazoliumbromide assay was used to analyze cell survival rate in vitro. Flow cytometry was performed to detect cell cycle and cell death. Scratch migration assay was used to evaluate cell migration and invasion. Western blot was performed to determine the expression levels of pro-apoptotic and anti apoptotic protein. RESULTS: In this study, we found that the survival rate reduced significantly in the combined group compared with the individual group and control group. The apoptosis-inducing effect of combined application was much more significant than that of individual application. The invasion ability of combined application was significantly lower than that of the individual application. In the combined group, there were high expression levels of pro apoptotic protein and low expression of anti-apoptotic protein. Cell-cycle analysis showed a change in the cell-cycle distribution and arrested cells in G2 M phase. CONCLUSION: In this study, we found that OD inhibited proliferation and induced apoptosis in the human osteosarcoma MG-63 cell line in a time-dependent and dose-dependent manner. In addition, OD displayed inhibitory activity on MG-63 cell proliferation and invasion and the study also showed that OD activity might be mediated by caspase activation. These data suggest that OD might represent a novel, efficient candidate agent for further experimentation in osteosarcoma treatment. PMID- 26834485 TI - ALK-positive anaplastic large cell lymphoma with prominent bone involvement in a 13-year-old boy. AB - INTRODUCTION: Anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL) is a type of non-Hodgkin lymphoma, which has strong expression of cluster of differentiation (CD)-30 and ALK. ALCL sometimes can involve the bone marrow, and in advanced stages, it can produce destructive bone lesions. But ALK+ ALCL with prominent bone involvement is very rare, especially in children. CASE REPORT: A 13-year-old boy presented with waist pain and low-grade fever for 8 months. The biopsy of soft tissue lesions around the thoracic spine showed that these cells were positive for ALK-1, CD30, leukocyte common antigen, CD3, CD4, and CD8, as well as being negative for epithelial membrane antigen and pan cytokeratin, which revealed ALCL. After six cycles of a regimen consisting of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone/methotrexate and cytarabine (hyper-CVAD/MA) and autologous hematopoietic stem cell transplantation, he achieved complete remission (CR). CONCLUSION: It is generally believed that the regimen consisting of cyclophosphamide, hydroxydaunorubicin (doxorubicin), vincristine, and prednisolone (CHOP) is also applicable to ALCL. Because of the tendency of rapid progression and the frequency of B symptoms, ALCL in children and young adults is treated with high-grade chemotherapy such as hyper-CVAD/MA. PMID- 26834486 TI - Polymorphisms in RAD51 and their relation with breast cancer in Saudi females. AB - The present study aimed at investigating the relationship between rs1801320 (G>C), rs1801321 (G>T), and rs2619681 (C>T) RAD51 gene polymorphisms and the risk of breast cancer development in Saudi females. The genotypes were analyzed using TaqMan genotyping assay and polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele frequencies were computed using chi-square or Fisher's exact test (two-tailed) by SPSS 21 software. The results showed that rs1801321G>T GG genotype and G allele frequency were strongly (P<0.0001) related to an elevated risk of breast cancer, while the mutant T allele appeared to provide protection against breast cancer development as observed from the significantly lower (P<0.0001) frequencies of the TT and GT genotypes in cancer patients compared to the healthy controls. The variant rs1801320G>C showed no significant differences in the frequencies of the genotypes and alleles in the patients and the control groups. The CC genotype and C allele frequency of rs2619681 (C>T) variant were significantly (P=0.012) higher in cancer patients, whereas the T allele showed a protective effect against cancer development. The frequencies of the three single-nucleotide polymorphisms did not differ in cancer patients with different tumor grades and human epidermal growth factor receptor 2 status (+ or -). However, the genotype frequency of rs1801320 (135G>C) differed in the patients with estrogen receptor (ER)+ and ER-, where CC genotype showed a significantly higher prevalence in the females with ER- who were suffering from breast cancer. In addition, the frequency of C allele of rs2619681 (C>T) was also significantly higher in the breast cancer patients who were ER+ and progesterone receptor (PR)+ compared to those with ER- and PR-. In the Saudi females, rs1801320 did not show an association with risk of breast cancer. Taken together, the results suggest that RAD51 rs1801321 polymorphism may be involved in the etiology of breast cancer in the Saudi females; however, further studies are necessary to confirm this relation. PMID- 26834487 TI - Telomerase reverse transcriptase methylation predicts lymph node metastasis and prognosis in patients with gastric cancer. AB - PURPOSE: Telomerase activity is associated with cellular immortalization and is present in most human tumors but absent in normal tissues. The activity of telomerase reverse transcriptase (TERT), a catalytic telomerase subunit, correlates with telomerase activity in tumors. The objective of this study was to investigate TERT promoter methylation and its prognostic impact in gastric cancer (GC). PATIENTS AND METHODS: The analysis of TERT promoter methylation was performed in tumors and corresponding normal tissues of 116 patients with GC using a highly sensitive Sequenom Epityper assay. The expression of TERT in GC tissues was measured by quantitative real-time polymerase chain reaction. RESULTS: The levels of TERT promoter methylation in GC samples were significantly higher than in normal adjacent tissues (P=0.002). Hypermethylation of TERT promoter was associated with high T-stage (P=0.024), late N-stage (P=0.006), and lymphovascular/neural invasion (P=0.035), without correlation with age, sex, or histological grade. Simple linear regression analysis showed that TERT mRNA correlated positively with TERT methylation (R (2)=0.562, P=0.001). Also, higher TERT mRNA expression was related to hypermethylation of TERT promoter in GC samples (P=0.005). Univariate analysis demonstrated that N-stage (P=0.002) and TERT promoter methylation (P=0.004) were predictive of overall survival. Furthermore, multivariate analysis confirmed that N-stage (P=0.013) and TERT promoter methylation (P=0.031) were independent prognostic indicators for overall survival. CONCLUSION: Our data suggested that hypermethylation of TERT promoter may contribute to gastric wall invasion, lymph node metastasis, lymphovascular/neural invasion, and poor prognosis in GC. GC patients with hypermethylation of TERT promoter could be eligible for close follow-up. PMID- 26834488 TI - WISP3 is highly expressed in a subset of colorectal carcinomas with a better prognosis. AB - Outlier genes with marked overexpression in subsets of cancers like ERBB2 have potential for the identification of gene classifiers and therapeutic targets for the appropriate subpopulation. In this study, using the cancer outlier profile analysis strategy, we identified WNT1-inducible-signaling pathway protein 3 (WISP3) as an outlier gene that is highly expressed in a subset of colorectal cancers (CRCs) from The Cancer Genome Atlas dataset. A meta-cancer outlier profile analysis and immunohistochemistry experiment to validate the outlier expression model of WISP3 in CRC was then performed. Our immunohistochemical results indicated that WISP3 was more frequently seen in the small tumors, and there was a significant association between its overexpression with a good prognosis. Furthermore, in the multivariable model, WISP3 outlier expression retained significance for overall survival. In summary, in this study, we identified an outlier gene WISP3 overexpressed in a subset of CRC having less aggressive characteristics and a better prognosis. We suggest WISP3 may provide more accurate and precise information regarding CRC population classification. PMID- 26834489 TI - The amplification of 1q21 is an adverse prognostic factor in patients with multiple myeloma in a Chinese population. AB - The prognostic heterogeneity of multiple myeloma (MM) is largely due to different genetic abnormalities. Cytogenetic analysis has revealed that most of MM harbor chromosome aberrations. Amplification of 1q21 is one of the most common chromosomal aberrations. Interphase fluorescence in situ hybridization was applied to detect the 1q21 amplification in 86 Chinese patients with newly diagnosed MM. Amp(1q21) was found in totally 40 of 86 (46.5%) cases, among which 29 with three copies of 1q21 and eleven with at least four copies of 1q21. Further analysis revealed a significant difference of overall survival and progression-free survival among the three arms (P<0.05). Bortezomib could not significantly improve the overall survival for patients with 1q21 amplification (P>0.05). These findings suggest that 1q21 amplification with four copies or more is prognostic factor for adverse outcomes of MM patients. Furthermore, chromosome 1q21 gains predicted a poor overall survival even in those receiving bortezomib based regimens. PMID- 26834490 TI - Expression of MECOM is associated with unfavorable prognosis in glioblastoma multiforme. AB - BACKGROUND: MDS1 and EVI1 complex locus protein EVI1 (MECOM) is an oncogenic transcription factor in several kinds of cancers. However, the clinical significance of MECOM in glioblastoma multiforme (GBM) has not been well elucidated. PATIENTS AND METHODS: Our study enrolled 86 resected samples of GBM in three medical centers. We detected the expression of MECOM in all the 86 samples by immunohistochemistry and compared the difference of MECOM mRNA between tumor tissues and adjacent tissues with real-time polymerase chain reaction. With immunoblotting, we detected the MECOM expression in different GBM cell lines. Moreover, we analyzed the correlation between MECOM expression and clinicopathologic factors with chi-square test, and evaluated the prognostic value of MECOM with univariate and multivariate analysis. RESULTS: In GBM tissue, the percentage of MECOM high expression is 41.9% (36/86). The mRNA of MECOM in tumor tissues is remarkably higher than that in adjacent tissues, indicating the oncogenic role of MECOM in GBM. MECOM exists in all the detected cell lines with different abundance. Moreover, MECOM is correlated with poorer overall survival rate (P=0.033) and can be identified as an independent prognostic factor in GBM (P=0.042). CONCLUSION: MECOM could be considered as an independent prognostic factor in GBM, predicting it as a potential and promising molecular drug target. PMID- 26834491 TI - Knockdown of TMEM16A suppressed MAPK and inhibited cell proliferation and migration in hepatocellular carcinoma. AB - TMEM16A plays an important role in cell proliferation in various cancers. However, less was known about the expression and role of TMEM16A in hepatocellular carcinoma. We screened the expression of TMEM16A in patients' hepatocellular carcinoma tissues, and also analyzed the biological function of hepatocellular carcinoma cells by knockdown of TMEM16A, as well as the expression of MAPK signaling proteins, including p38, p-p38, ERK1/2, p-ERK1/2, JNK, and p JNK, and cell cycle regulatory protein cyclin D1 in TMEM16A siRNA-transfected SMMC-7721 cells by Western blot. Our results showed that TMEM16A was overexpressed in hepatocellular carcinoma tissues. Inhibition of TMEM16A suppressed the cell proliferation, migration, and invasion, and cell cycle progression but did not influence the cell apoptosis. TMEM16A siRNA-suppressed cancer cell proliferation and tumor growth were accompanied by a reduction of p38 and ERK1/2 activation and cyclin D1 induction, and were not influenced by other tested MAPK signaling proteins. In addition, inhibition of TMEM16A suppressed tumorigenicity in vivo. TMEM16A is overexpressed in hepatocellular carcinoma, and that inhibition of TMEM16A suppressed MAPK and growth of hepatocellular carcinoma. TMEM16A could be a potentially novel therapeutic target for human cancers, including hepatocellular carcinoma. PMID- 26834492 TI - Functional divergence and convergence between the transcript network and gene network in lung adenocarcinoma. AB - INTRODUCTION: Alternative RNA splicing is a critical regulatory mechanism during tumorigenesis. However, previous oncological studies mainly focused on the splicing of individual genes. Whether and how transcript isoforms are coordinated to affect cellular functions remain underexplored. Also of great interest is how the splicing regulome cooperates with the transcription regulome to facilitate tumorigenesis. The answers to these questions are of fundamental importance to cancer biology. RESULTS: Here, we report a comparative study between the transcript-based network (TN) and the gene-based network (GN) derived from the transcriptomes of paired tumor-normal tissues from 77 lung adenocarcinoma patients. We demonstrate that the two networks differ significantly from each other in terms of patient clustering and the number and functions of network modules. Interestingly, the majority (89.5%) of multi-transcript genes have their transcript isoforms distributed in at least two TN modules, suggesting regulatory and functional divergences between transcript isoforms. Furthermore, TN and GN modules share only50%-60% of their biological functions. TN thus appears to constitute a regulatory layer separate from GN. Nevertheless, our results indicate that functional convergence and divergence both occur between TN and GN, implying complex interactions between the two regulatory layers. Finally, we report that the expression profiles of module members in both TN and GN shift dramatically yet concordantly during tumorigenesis. The mechanisms underlying this coordinated shifting remain unclear yet are worth further explorations. CONCLUSION: We show that in lung adenocarcinoma, transcript isoforms per se are coordinately regulated to conduct biological functions not conveyed by the network of genes. However, the two networks may interact closely with each other by sharing the same or related biological functions. Unraveling the effects and mechanisms of such interactions will significantly advance our understanding of this deadly disease. PMID- 26834493 TI - Untreated newly diagnosed essential hypertension is associated with nonalcoholic fatty liver disease in a population of a hypertensive center. AB - PURPOSE: Recent studies have demonstrated that hypertension (HTN) is associated with nonalcoholic fatty liver disease (NAFLD) in treated hypertensive patients. The aim of this study was to investigate the association between newly diagnosed essential HTN and NAFLD in untreated hypertensive patients. PATIENTS AND METHODS: A consecutive series of 240 subjects (143 hypertensives and 97 normotensives), aged 30-80 years, without diabetes mellitus were enrolled in the study. Subjects with 24-hour systolic blood pressure (SBP) values >=130 mmHg and/or diastolic BP values >=80 mmHg were defined as hypertensives. NAFLD was defined as the presence of liver hyperechogenicity on ultrasound. RESULTS: Body mass index (P=0.002) and essential HTN (P=0.016) were independently associated with NAFLD in the multivariate logistic regression model. Furthermore, the multivariate analysis revealed that morning SBP (P=0.044) was independently associated with NAFLD. CONCLUSION: Untreated, newly diagnosed essential HTN is independently associated with NAFLD. Ambulatory BP monitoring could be used for the diagnosis of essential HTN in patients with NAFLD. PMID- 26834494 TI - Electrical stimulation for gastroesophageal reflux disease: current state of the art. AB - Patients with gastroesophageal reflux disease (GERD) who are not satisfied with acid suppression therapy can benefit primarily from fundoplication, a surgical intervention. Fundoplication has been the standard surgical procedure for GERD. It is effective but is associated with adverse effects, resulting in a declining number of interventions, creating a need for alternative interventions that are effective, yet have a better adverse effect profile. One such alternative involves the application of electrical stimulation to the lower esophageal sphincter. A number of animal studies showed that such stimulation can increase resting lower esophageal sphincter pressure. An acute human study confirmed this effect, and was followed by two open-label studies, with a follow-up of up to 3 years. Results thus far show that the therapy is associated with a significant improvement in symptoms, a significant reduction in esophageal acid exposure, and a very good safety profile. This review will describe the evolution of electrical stimulation therapy for GERD, as well as the safety and efficacy of this intervention. PMID- 26834495 TI - Case report of individual with cutaneous immunodeficiency and novel 1p36 duplication. AB - INTRODUCTION: Crusted or Norwegian scabies is an infectious skin dermatopathology usually associated with an underlying immunodeficiency condition. It is caused when the mite Sarcoptes scabiei infects the skin, and the immune system is unable to control its spread, leading to a massive hyperinfestation with a simultaneous inflammatory and hyperkeratotic reaction. This is the first report of a novel 1p36 duplication associated with a recurrent infection of crusted scabies. CASE REPORT: We describe a 34-year-old patient with a cutaneous immunodeficiency characterized by recurrent crusted scabies infestation, diffuse tinea, and recurrent staphylococcal cellulitis, who we suspected had an undiagnosed syndrome. The patient also suffered from mental retardation, renal failure, and premature senescence. A cytogenetic fluorescence in situ hybridization analysis revealed a 9.34 Mb duplication within the short (p) arm of chromosome 1, precisely from 1p36.11 to 1p36.21, with an adjacent 193 kb copy gain entirely within 1p36.11. In addition, chromosome 4 had a 906 kb gain in 4p16.1 and chromosome 9 had a 81 kb copy gain in 9p24.3. Over 100 genes localized within these duplicated regions. Gene expression array revealed 82 genes whose expression changed >1.5-fold compared to a healthy age-matched skin control, but among them only the lipolytic enzyme arylacetamide deacetylase-like 3 was found within the duplicated 1p36 region of chromosome 1. DISCUSSION: Although genetic duplications in the 1p36 region have been previously described, our report describes a novel duplicative variant within the 1p36 region. The patient did not have a past history of immunosuppression but was afflicted by a recurrent case of crusted scabies, raising the possibility that the recurrent infection was associated with the 1p36 genetic duplication. CONCLUSION: To our knowledge, the specific duplicated sequence between 1p36.11 and p36.21 found in our patient has never been previously reported. We reviewed and compared the clinical, genotyping, and gene microarray results of our patient in order to characterize this novel 1p36 duplication syndrome, which might have contributed to the recurrent scabies infection in this patient. PMID- 26834496 TI - A retrospective study on persistent pain after childbirth in the Netherlands. AB - Reported prevalence rates of persistent postpartum pain (PPP) range from less than 1% to almost 20%. The aim of this study was to examine the prevalence of PPP in a Dutch cohort and to evaluate a possible causal role for specific risk factors on the development of chronic pain after childbirth. A questionnaire was sent to 960 postpartum women approximately 2 years after delivery. Primary outcome was pain that arose from childbirth at follow-up, and secondary outcomes included quality of life (QoL) and Hospital Anxiety and Depression Scale scores. Tested risk factors included mode of labor analgesia, history of negative effect, history of chronic pain, delivery route, parity, and ethnicity. A total of 495 (51.6%) women participated. At a mean time of 2.3 postpartum years, 7.3% of women reported any pain and 6.1% reported significant pain related to the delivery. Compared to spontaneous delivery, cesarean delivery provided protection against persistent pain (odds ratio, 0.12; 95% CI, 0.01-0.63, P<0.05). None of the other risk factors, including remifentanil use for labor pain, were of influence on the prevalence of persistent pain. Women with PPP experienced greater negative effects and had lower QoL scores compared to women without pain. In this cohort of Dutch patients, PPP is a serious problem with a great impact on the physical and mental health of women. PMID- 26834497 TI - Failed back surgery syndrome: review and new hypotheses. AB - Failed back surgery syndrome (FBSS) is a term used to define an unsatisfactory outcome of a patient who underwent spinal surgery, irrespective of type or intervention area, with persistent pain in the lumbosacral region with or without it radiating to the leg. The possible reasons and risk factors that would lead to FBSS can be found in distinct phases: in problems already present in the patient before a surgical approach, such as spinal instability, during surgery (for example, from a mistake by the surgeon), or in the postintervention phase in relation to infections or biomechanical alterations. This article reviews the current literature on FBSS and tries to give a new hypothesis to understand the reasons for this clinical problem. The dysfunction of the diaphragm muscle is a component that is not taken into account when trying to understand the reasons for this syndrome, as there is no existing literature on the subject. The diaphragm is involved in chronic lower back and sacroiliac pain and plays an important role in the management of pain perception. PMID- 26834499 TI - A young man with concurrent acute appendicitis and incarcerated right indirect inguinal hernia. AB - OBJECTIVE: Acute appendicitis and incarcerated hernia rarely present in the same episode. Our study reports patient presentation, diagnosis method, and treatment of an unusual case at the Chiang Mai University Hospital. METHOD: Case report. RESULT: A 20-year-old man visited the Chiang Mai University Hospital with right lower quadrant pain and a right groin mass which could not be reduced. The computerized tomography scan showed acute appendicitis and omentum in the hernia sac. Operative treatment was an appendectomy and herniorrhaphy. The treatment was successful, and the patient was discharged from our hospital without any complications. CONCLUSION: Concurrent acute appendicitis and incarcerated hernia are very rare, but should be kept in mind if a patient presents with right lower quadrant pain and a right groin mass. Further investigation may be helpful if the diagnosis is uncertain. Operative priority treatment depends on each individual case. PMID- 26834498 TI - Perspectives on menopause and women with HIV. AB - Since the implementation of effective combination antiretroviral therapy, HIV infection has been transformed from a life-threatening condition into a chronic disease. As people with HIV are living longer, aging and its associated manifestations have become key priorities as part of HIV care. For women with HIV, menopause is an important part of aging to consider. Women currently represent more than one half of HIV-positive individuals worldwide. Given the vast proportion of women living with HIV who are, and will be, transitioning through age-related life events, the interaction between HIV infection and menopause must be addressed by clinicians and researchers. Menopause is a major clinical event that is universally experienced by women, but affects each individual woman uniquely. This transitional time in women's lives has various clinical implications including physical and psychological symptoms, and accelerated development and progression of other age-related comorbidities, particularly cardiovascular disease, neurocognitive dysfunction, and bone mineral disease; all of which are potentially heightened by HIV or its treatment. Furthermore, within the context of HIV, there are the additional considerations of HIV acquisition and transmission risk, progression of infection, changes in antiretroviral pharmacokinetics, response, and toxicities. These menopausal manifestations and complications must be managed concurrently with HIV, while keeping in mind the potential influence of menopause on the prognosis of HIV infection itself. This results in additional complexity for clinicians caring for women living with HIV, and highlights the shifting paradigm in HIV care that must accompany this aging and evolving population. PMID- 26834501 TI - Impact of tofacitinib on patient outcomes in rheumatoid arthritis - review of clinical studies. AB - Rheumatoid arthritis is a chronic, progressive autoimmune disease associated with inflammation and destruction of joints and systemic effects, which result in significant impact on patient's quality of life and function. Tofacitinib was approved for the treatment of rheumatoid arthritis in the USA in 2012 and subsequently in other countries, but not by the European Medicines Agency. The goal of this review was to evaluate the impact of tofacitinib on patient-reported and patient-specific outcomes from prior clinical studies, focusing on quality of life, functionality, pain, global disease assessment, major adverse consequences, and withdrawals. A total of 13 reports representing 11 clinical studies on tofacitinib in rheumatoid arthritis were identified through PubMed and reference lists in meta-analyses and other reviews. Data on improvements in patient-driven composite tools to measure disease activity in rheumatoid arthritis, such as the Health Assessment Questionnaire, served as a major outcome evaluated in this review and were extracted from each study. Additional data extracted from those clinical studies included patient assessment of pain (using a 0-100 mm visual analog scale), patient global assessment of disease (using a 0-100 mm visual analog scale), patient withdrawals, withdrawals due to adverse effects or lack of effect, and risk of serious adverse effects, serious infections, and deaths. Tofacitinib 5 mg bid appears to have a favorable impact on patient outcomes related to efficacy and safety when compared with baseline values and with comparator disease-modifying antirheumatic drugs and placebo. Improvements were seen in the composite and individual measures of disease activity. Serious adverse effects, other adverse consequences, overall withdrawals, and withdrawals due to adverse effects and lack of efficacy are similar or more favorable for tofacitinib versus comparator disease-modifying antirheumatic drugs and placebo. At this point, tofacitinib appears to have an important role in the treatment of rheumatoid arthritis through improvement in these patient outcomes. However, it may require years of additional clinical studies and postmarketing surveillance to fully characterize the benefit-to-risk ratio of tofacitinib in a larger and diverse patient population. PMID- 26834502 TI - Sonography and hypotension: a change to critical problem solving in undergraduate medical education. AB - STUDY OBJECTIVES: Multiple curricula have been designed to teach medical students the basics of ultrasound; however, few focus on critical problem-solving. The objective of this study is to determine whether a theme-based ultrasound teaching session, dedicated to the use of ultrasound in the management of the hypotensive patient, can impact medical students' ultrasound education and provide critical problem-solving exercises. METHODS: This was a cross-sectional study using an innovative approach to train 3rd year medical students during a 1-day ultrasound training session. The students received a 1-hour didactic session on basic ultrasound physics and knobology and were also provided with YouTube hyperlinks, and links to smart phone educational applications, which demonstrated a variety of bedside ultrasound techniques. In small group sessions, students learned how to evaluate patients for pathology associated with hypotension. A knowledge assessment questionnaire was administered at the end of the session and again 3 months later. Student knowledge was also assessed using different clinical scenarios with multiple-choice questions. RESULTS: One hundred and three 3rd year medical students participated in this study. Appropriate type of ultrasound was selected and accurate diagnosis was made in different hypotension clinical scenarios: pulmonary embolism, 81% (95% CI, 73%-89%); abdominal aortic aneurysm, 100%; and pneumothorax, 89% (95% CI, 82%-95%). The average confidence level in performing ultrasound-guided central line placement was 7/10, focused assessment with sonography for trauma was 8/10, inferior vena cava assessment was 8/10, evaluation for abdominal aortic aneurysm was 8/10, assessment for deep vein thrombus was 8/10, and cardiac ultrasound for contractility and overall function was 7/10. Student performance in the knowledge assessment portion of the questionnaire was an average of 74% (SD =11%) at the end of workshop and 74% (SD =12%) 3 months later (P=0.00). CONCLUSION: At our institution, we successfully integrated ultrasound and critical problem-solving instruction, as part of a 1 day workshop for undergraduate medical education. PMID- 26834504 TI - Integrating medical simulation programs into the Turkish undergraduate medical curriculum. PMID- 26834503 TI - Perceived stress at transition to workplace: a qualitative interview study exploring final-year medical students' needs. AB - OBJECTIVES: This study was designed to explore final-year medical students' stressors and coping strategies at the transition to the clinical workplace. METHODS: In this qualitative study, semi-standardized interviews with eight final year medical students (five male, three female; aged 25.9+/-1.4 years) were conducted during their internal medicine rotation. After verbatim transcription, a qualitative content analysis of students' impressions of stress provoking and easing factors during final-year education was performed. RESULTS: Students' statements regarding burdens and dealing with stress were classified into four main categories: A) perceived stressors and provoking factors, B) stress-induced consequences, C) personal and external resources for preventing and dealing with stress, and D) final-year students' suggestions for workplace improvement. CONCLUSION: Final-year medical students perceived different types of stress during their transition to medical wards, and reported both negative consequences and coping resources concerning perceived stress. As supervision, feedback, and coping strategies played an important role in the students' perception of stress, final-year medical education curricula development should focus on these specifically. PMID- 26834500 TI - Clinical management of sleep disturbances in Alzheimer's disease: current and emerging strategies. AB - Sleep and circadian disorders in Alzheimer's disease (AD) are more frequent than in the general population and appear early in the course of the disease. Quality of sleep and quality of life are parallel in these patients, and such disorders also represent a heavy burden for caregivers. Although alterations in melatonin and hypocretins (orexins) seem to play a key role in the origin of these disturbances, the etiology of these disorders is multifactorial, including many factors such as environment, behavior, treatments, and comorbidities, among others. A comprehensive evaluation of sleep in each patient is essential in the design of the treatment that includes nonpharmacological and pharmacological approaches. One particularly interesting point is the possibility of a role of sleep disorders in the pathogenesis of AD, raising the possibility that treating the sleep disorder may alter the course of the disease. In this review, we present an update on the role of sleep disorders in AD, the bidirectional influence of sleep problems and AD, and treatment options. Behavioral measures, bright light therapy (BLT), melatonin, and other drugs are likely well known and correctly managed by the physicians in charge of these patients. In spite of the multiple treatments used, evidence of efficacy is scarce and more randomized double-blind placebo-controlled studies are needed. Future directions for treatment are the establishment of BLT protocols and the development of drugs with new mechanisms of action, especially hypocretin receptor antagonists, melatonin receptor agonists, and molecules that modulate the circadian clock. PMID- 26834505 TI - Rapid scan electron paramagnetic resonance at 1.0 GHz of defect centers in gamma irradiated organic solids. AB - The radicals in six 60Co gamma-irradiated solids: malonic acid, glycylglycine, 2,6 di-t-butyl 4-methyl phenol, L-alanine, dimethyl malonic acid, and 2-amino isobutyric acid, were studied by rapid scan electron paramagnetic resonance at L band (1.04 GHz) using a customized Bruker Elexsys spectrometer and a locally designed dielectric resonator. Sinusoidal scans with widths up to 18.2 mT were generated with the recently described coil driver and Litz wire coils. Power saturation curves showed that the rapid scan signals saturated at higher powers than did conventional continuous wave signals. The rapid scan data were deconvolved and background subtracted to obtain absorption spectra. For the same data acquisition time the signal-to-noise for the absorption spectra obtained in rapid scans were 23 to 37 times higher than for first-derivative spectra obtained by conventional continuous wave electron paramagnetic resonance. PMID- 26834506 TI - Semiparametric Estimation in the Secondary Analysis of Case-Control Studies. AB - We study the regression relationship among covariates in case-control data, an area known as the secondary analysis of case-control studies. The context is such that only the form of the regression mean is specified, so that we allow an arbitrary regression error distribution, which can depend on the covariates and thus can be heteroscedastic. Under mild regularity conditions we establish the theoretical identifiability of such models. Previous work in this context has either (a) specified a fully parametric distribution for the regression errors, (b) specified a homoscedastic distribution for the regression errors, (c) has specified the rate of disease in the population (we refer this as true population), or (d) has made a rare disease approximation. We construct a class of semiparametric estimation procedures that rely on none of these. The estimators differ from the usual semiparametric ones in that they draw conclusions about the true population, while technically operating in a hypothetic superpopulation. We also construct estimators with a unique feature, in that they are robust against the misspecification of the regression error distribution in terms of variance structure, while all other nonparametric effects are estimated despite of the biased samples. We establish the asymptotic properties of the estimators and illustrate their finite sample performance through simulation studies, as well as through an empirical example on the relation between red meat consumption and heterocyclic amines. Our analysis verified the positive relationship between red meat consumption and two forms of HCA, indicating that increased red meat consumption leads to increased levels of MeIQA and PhiP, both being risk factors for colorectal cancer. Computer software as well as data to illustrate the methodology are available at http://wileyonlinelibrary.com/journal/rss-datasets. PMID- 26834507 TI - Relative Influence of Various Forms of Partner Violence on the Health of Male Victims: Study of a Helpseeking Sample. AB - Researchers argue that partner violence (PV) is a multidimensional and heterogeneous phenomenon that needs to be measured in multiple ways to capture its range, extent, severity, and potential consequences. Several large scale, population-based studies show that about 40%-50% of PV victims in a one-year time period are men; this finding is consistent whether the study focuses on physical PV or a combination of several forms of PV. However, no one has investigated how the different forms of PV contribute to male victims' poor mental health, although research suggests that physical, psychological, and sexual PV contribute unique variance to female victims' poor health. The current study investigated how six forms of PV - physical, sexual, severe psychological, controlling, legal/administrative (LA), and injury - contributed to the poor health of 611 male victims of PV who sought help. We found that the combination of PV contributed significant unique variance to men's depression, post-traumatic stress disorder, physical health, and poor health symptoms, after controlling for demographic and other traumatic experiences. The common variance among the forms of PV victimization was the strongest contributor to victims' poor health; the types of PV that contributed the most unique variance were controlling behaviors, LA aggression, sexual aggression, and injury. Discussion focuses on the research and practice implications of these findings. PMID- 26834508 TI - The Effects of Vignette Placement on Attitudes Toward Supporting Family Members. AB - : Vignettes are useful for measuring norms and beliefs, but little is known about how vignette placement affects responses to subsequent attitude questions. We investigate how the placement of a vignette about parents and adult children living together affects answers to subsequent questions about family obligations in a survey of the U.S. POPULATION: We randomly assigned the order of the vignette and three single-statement attitude questions. For the single-statement question about family members living together, the effect of vignette placement depended on respondents' original attitudes. For individuals with ambivalent or positive attitudes, asking the vignette before the attitude questions doubled reports of favorable attitudes. Vignette placement had no effect for those with negative attitudes. For the single-statement attitude questions about financial support between parents and adult children, vignette placement had no effect, suggesting that vignette placement may only influence subsequent questions about the same topic. PMID- 26834510 TI - The huge Package for High-dimensional Undirected Graph Estimation in R. AB - We describe an R package named huge which provides easy-to-use functions for estimating high dimensional undirected graphs from data. This package implements recent results in the literature, including Friedman et al. (2007), Liu et al. (2009, 2012) and Liu et al. (2010). Compared with the existing graph estimation package glasso, the huge package provides extra features: (1) instead of using Fortan, it is written in C, which makes the code more portable and easier to modify; (2) besides fitting Gaussian graphical models, it also provides functions for fitting high dimensional semiparametric Gaussian copula models; (3) more functions like data-dependent model selection, data generation and graph visualization; (4) a minor convergence problem of the graphical lasso algorithm is corrected; (5) the package allows the user to apply both lossless and lossy screening rules to scale up large-scale problems, making a tradeoff between computational and statistical efficiency. PMID- 26834509 TI - Surface Reconstructions in Organic Crystals: Simulations of the Effect of Temperature and Defectivity on Bulk and (001) Surfaces of 2,2':6',2" Ternaphthalene. AB - 2,2':6',2"-Ternaphthalene (NNN) is a novel, blue-emitting material, suitable for preparation of organic light-emitting diodes. Its crystal structure has been solved recently, but its thermal behavior and surface properties have not yet been explored, partly due to the difficulty in obtaining high quality crystals. In the present study we use classical molecular dynamics to investigate the thermal behavior of bulk and (001) surfaces of NNN. Our bulk simulations indicate the occurrence of a phase transition at about 600 K. The transition is facilitated by the presence of a free (001) surface, since a reconstruction leading to a very similar structure occurs around 550 K in our surface models. This holds for both ideal and defective surface models, containing a small number of vacancies (one or two missing molecules in the outermost layer). In all cases, the process is triggered by thermal motion and involves the reorientation of the molecules with respect to the (001) plane. Both the bulk and surface phases share the monoclinic space group P21/a with a herringbone disposition of molecules. These findings and their implications for the use of NNN in organic electronics are discussed. PMID- 26834512 TI - CAreDroid: Adaptation Framework for Android Context-Aware Applications. AB - Context-awareness is the ability of software systems to sense and adapt to their physical environment. Many contemporary mobile applications adapt to changing locations, connectivity states, available computational and energy resources, and proximity to other users and devices. Nevertheless, there is little systematic support for context-awareness in contemporary mobile operating systems. Because of this, application developers must build their own context-awareness adaptation engines, dealing directly with sensors and polluting application code with complex adaptation decisions. In this paper, we introduce CAreDroid, which is a framework that is designed to decouple the application logic from the complex adaptation decisions in Android context-aware applications. In this framework, developers are required- only-to focus on the application logic by providing a list of methods that are sensitive to certain contexts along with the permissible operating ranges under those contexts. At run time, CAreDroid monitors the context of the physical environment and intercepts calls to sensitive methods, activating only the blocks of code that best fit the current physical context. CAreDroid is implemented as part of the Android runtime system. By pushing context monitoring and adaptation into the runtime system, CAreDroid eases the development of context-aware applications and increases their efficiency. In particular, case study applications implemented using CAre-Droid are shown to have: (1) at least half lines of code fewer and (2) at least 10* more efficient in execution time compared to equivalent context-aware applications that use only standard Android APIs. PMID- 26834511 TI - Identifying HIV-Infected Women's Psychosocial Stressors: Findings from a Qualitative Study. AB - To inform future psychosocial interventions for HIV-infected women, five focus groups were conducted with 29 HIV-infected women (72% African-American). Sessions were audio-recorded, transcribed, and coded by two raters. HIV-specific stressors included difficulties with serostatus disclosure, HIV medication adherence, and HIV-related discrimination. Stressors not directly linked to HIV were described as more concerning and included mental health or substance use problems, relationship challenges, caretaking for children or grandchildren, and financial difficulties. Participants suggested that interventions provide social support from other HIV-infected women, consistent case management and social work services, and forums to acquire additional information about HIV and treatment options. PMID- 26834513 TI - Analysis of bone marrow plasma cells in patients with solitary bone plasmacytoma. AB - Local radiotherapy is the treatment of choice for solitary bone plasmacytoma (SBP) and the role of adjuvant systemic chemotherapy in preventing progression to multiple myeloma (MM) is controversial. The purpose of this study was to examine the presence of systemic disease in the form of neoplastic plasma cells (PC) in bone marrow of patients with SBP. Flow cytometric immunophenotyping of PC was carried out on bone marrow aspirate of 7 patients using monoclonal antibodies: CD19 FITC, CD45 FITC, CD20 FITC, CD52 PE, CD117 PE, CD56 PE, CD38 PerCP-Cy5.5, CD138 APC, anti-kappa (kappa) FITC and anti-lambda (lambda) PE. The neoplastic as well as normal PC were identified in bone marrow aspirate of all the patients at the time of diagnosis; the neoplastic PC ranged from 0.1%to 0.7% of all BM cells and 33.5% to 89.7% of total BMPC. The kappa:lambda ratio was normal in all the samples ranging from 0.5% to 1.6%. The present work shows the presence of systemic disease in the form of neoplastic PC in bone marrow of patients with SBP. Prospective studies would be required to study if the levels of neoplastic PC in the bone marrow may help us identify patients who are likely to progress to overt MM and benefit from systemic chemotherapy. PMID- 26834514 TI - Incorporation of omics analyses into artificial gravity research for space exploration countermeasure development. AB - The next major steps in human spaceflight include flyby, orbital, and landing missions to the Moon, Mars, and near earth asteroids. The first crewed deep space mission is expected to launch in 2022, which affords less than 7 years to address the complex question of whether and how to apply artificial gravity to counter the effects of prolonged weightlessness. Various phenotypic changes are demonstrated during artificial gravity experiments. However, the molecular dynamics (genotype and molecular phenotypes) that underlie these morphological, physiological, and behavioral phenotypes are far more complex than previously understood. Thus, targeted molecular assessment of subjects under various G conditions can be expected to miss important patterns of molecular variance that inform the more general phenotypes typically being measured. Use of omics methods can help detect changes across broad molecular networks, as various G-loading paradigms are applied. This will be useful in detecting off-target, or unanticipated effects of the different gravity paradigms applied to humans or animals. Insights gained from these approaches may eventually be used to inform countermeasure development or refine the deployment of existing countermeasures. This convergence of the omics and artificial gravity research communities may be critical if we are to develop the proper artificial gravity solutions under the severely compressed timelines currently established. Thus, the omics community may offer a unique ability to accelerate discovery, provide new insights, and benefit deep space missions in ways that have not been previously considered. PMID- 26834516 TI - Immunotoxin - a new treatment option in patients with relapsed and refractory Hodgkin lymphoma. AB - BACKGROUND: Even though Hodgkin lymphoma is a highly curable disease, some of the patients have either a refractory disease or experience a relapse following a successful primary therapy. Durable responses and remissions in patients with relapsed or refractory disease may be achieved in approximately one-half with salvage chemotherapy followed by high dose chemotherapy (HDT) and autologous hematopoietic cell rescue (SCT). On the other hand, patients who relapse after HDT and autologous SCT or those who have failed at least two prior multi-agent chemotherapy regimens and are not candidates for HDT have limited treatment options. CONCLUSIONS: A new treatment option in this population is an immunotoxin Brentuximab vedotin composed of a CD30 directed antibody linked to the antitubulin agent monomethyl auristatin E. It has demonstrated a substantial effectiveness and an acceptable toxicity. In the pivotal study, the overall response rate was 75% with 34% of complete remissions. The median durations of response were 20.5 and 6.7 months for those with complete remission and all responding patients, respectively. The median overall survival was 40.5 months (3 years overall survival 54%) and the median progression-free survival 9.3 months. The most common non-hematologic toxicities were peripheral sensory neuropathy, nausea, and fatigue while the most common severe side effects were neutropenia, thrombocytopenia, anemia, and peripheral sensory neuropathy. PMID- 26834517 TI - [F-18] FDG-PET/CT parameters as predictors of outcome in inoperable NSCLC patients. AB - BACKGROUND: We evaluated the prognostic significance of standardized uptake value (SUVmax), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) in [F 18] FDG PET/CT findings in patients with inoperable non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred and three patients (mean age, 65.6 +/- 16 years) underwent [F-18] FDG PET/CT before the chemotherapy. The SUVmax value, the MTV (cm(3); 42% threshold) and the TLG (g) were registered. The patients were followed up to 18 months thereafter (range 12-55 months). Failure to respond without progression, progression and/or disease-related death constituted surrogate end-points. The optimal SUVmax, MTV and TLG cut-off to predict the patients' outcome were estimated. PET/CT results were then related to disease outcome (progression free survival; PFS). RESULTS: The Kaplan-Meier survival analysis for SUVmax showed a significant shorter PFS in patients presenting with lower values as compared to those with higher (p < 0.05, log-rank test). MTV and TLG were not suitable for predicting PFS apart from the subset of patients with mediastinal nodal involvement. CONCLUSIONS: Despite the availability of new tools for the quantitative assessment of disease activity on PET/CT, the SUVmax rather than MTV and TLG remains the only predictor for PFS in NSCLC patients. MTV holds a value only when concomitant nodal involvement occurs. PMID- 26834518 TI - Optimal scan time for evaluation of parathyroid adenoma with [(18)F] fluorocholine PET/CT. AB - BACKGROUND: Parathyroid adenomas, the most common cause of primary hyperparathyroidism, are benign tumours which autonomously produce and secrete parathyroid hormone. [(18)F]-fluorocholine (FCH), PET marker of cellular proliferation, was recently demonstrated to accumulate in lesions representing enlarged parathyroid tissue; however, the optimal time to perform FCH PET/CT after FCH administration is not known. The aim of this study was to determine the optimal scan time of FCH PET/CT in patients with primary hyperparathyroidism. PATIENTS AND METHODS: 43 patients with primary hyperparathyroidism were enrolled in this study. A triple-phase PET/CT imaging was performed five minutes, one and two hours after the administration of FCH. Regions of interest (ROI) were placed in lesions representing enlarged parathyroid tissue and thyroid tissue. Standardized uptake value (SUVmean), retention index and lesion contrast for parathyroid and thyroid tissue were calculated. RESULTS: Accumulation of FCH was higher in lesions representing enlarged parathyroid tissue in comparison to the thyroid tissue with significantly higher SUVmean in the second and in the third phase (p < 0.0001). Average retention index decreased significantly between the first and the second phase and increased significantly between the second and the third phase in lesions representing enlarged parathyroid tissue and decreased significantly over all three phases in thyroid tissue (p< 0.0001). The lesion contrast of lesions representing enlarged parathyroid tissue and thyroid tissue was significantly better in the second and the third phase compared to the first phase (p < 0.05). CONCLUSIONS: According to the results the optimal scan time of FCH PET/CT for localization of lesions representing enlarged parathyroid tissue is one hour after administration of the FCH. PMID- 26834519 TI - Endobronchial ultrasound elastography strain ratio for mediastinal lymph node diagnosis. AB - BACKGROUND: Ultrasound elastography is an imaging procedure that can assess the biomechanical characteristics of different tissues. The aim of this study was to define the diagnostic value of the endobronchial ultrasound (EBUS) elastography strain ratio of mediastinal lymph nodes in patients with a suspicion of lung cancer. The diagnostic values of the strain ratios were compared with the EBUS brightness mode (B-mode) features of selected mediastinal lymph nodes and with their cytological diagnoses. PATIENTS AND METHODS: This prospective, single centre study enrolled patients with an indication for biopsy and mediastinal staging after a non-invasive diagnostic workup of a lung tumour. EBUS with standard B-mode evaluation and elastography with strain ratio measurement were performed before endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). RESULTS: Thirty-three patients with 80 suspicious mediastinal lymph nodes were included. Malignant infiltration was confirmed in 34 (42.5%) lymph nodes. The area under the receiver operating characteristic curve for the strain ratio was 0.87 (p < 0.0001). At a strain ratio >= 8, the accuracy for malignancy prediction was 86.25% (sensitivity 88.24%, specificity 84.78%, positive predictive value [PPV] 81.08%, negative predictive value [NPV] 90.70%). The strain ratio is more accurate than conventional B-mode EBUS modalities for differentiating between malignant and benign lymph nodes. CONCLUSIONS: EBUS guided elastography with strain ratio assessment can distinguish malignant from benign mediastinal lymph nodes with greater accuracy than conventional EBUS modalities. This new method may reduce the number of mediastinal EBUS-TBNAs and thus reduce the invasiveness and expense of mediastinal staging in patients with non-small lung cancer (NSCLC). PMID- 26834520 TI - Analysis of risk factors for perifocal oedema after endovascular embolization of unruptured intracranial arterial aneurysms. AB - BACKGROUND: Endovascular embolization is a treatment of choice for the management of unruptured intracranial aneurysms, but sometimes is complicated with perianeurysmal oedema. The aim of our study was to establish incidence and outcomes of perianeurysmal oedema after endovascular coiling of unruptured intracranial aneurysms, and to reveal possible risk factors for development of this potentially serious complication. METHODS: In total 119 adult patients with endovascular embolization of unruptured intracranial aneurysm (performed at Department for Interventional Neuroradiology, Clinical Center, Kragujevac, Serbia) were included in our study. The embolizations were made by electrolite detachable platinum coils: pure platinum, hydrophilic and combination of platinum and hydrophilic coils. Primary outcome variable was perianeurysmal oedema visualized by magnetic resonance imaging (MRI) 7, 30 and 90 days after the embolization. RESULTS: The perianurysmal oedema appeared in 47.6% of patients treated with hydrophilic coils, in 21.6% of patients treated with platinum coils, and in 53.8% of those treated with mixed type of the coils. The multivariate logistic regression showed that variables associated with occurrence of perianeurysmal oedema are volume of the aneurysm, hypertension, diabetes and smoking habit. Hypertension is the most important independent predictor of the perianeurysmal oedema, followed by smoking and diabetes. CONCLUSIONS: The results of our study suggest that older patients with larger unruptured intracranial aneurysms, who suffer from diabetes mellitus and hypertension, and have the smoking habit, are under much higher risk of having perianeurysmal oedema after endovascular coiling. PMID- 26834521 TI - Estimation of cell response in fractionation radiotherapy using different methods derived from linear quadratic model. AB - BACKGROUND: The aim of this study was to use various theoretical methods derived from the Linear Quadratic (LQ) model to calculate the effects of number of subfractions, time intervals between subfractions, dose per subfraction, and overall fraction time on the cells' survival. Comparison of the results with experimental outcomes of melanoma and breast adenocarcinoma cells was also performed. Finally, the best matched method with experimental outcomes is introduced as the most accurate method in predicting the cell response. MATERIALS AND METHODS: The most widely used theoretical methods in the literature, presented by Keall et al., Brenner, and Mu et al., were used to calculate the cells' survival following radiotherapy with different treatment schemes. The overall treatment times were ranged from 15 to 240 minutes. To investigate the effects of number of subfractions and dose per subfraction, the cells' survival after different treatment delivery scenarios were calculated through fixed overall treatment times of 30, 60 and 240 minutes. The experimental tests were done for dose of 4 Gy. The results were compared with those of the theoretical outcomes. RESULTS: The most affective parameter on the cells' survival was the overall treatment time. However, the number of subfractions per fractions was another effecting parameter in the theoretical models. This parameter showed no significant effect on the cells' survival in experimental schemes. The variations in number of subfractions per each fraction showed different results on the cells' survival, calculated by Keall et al. and Brenner methods (P<0.05). CONCLUSIONS: Mu et al. method can predict the cells' survival following fractionation radiotherapy more accurately than the other models. Using Mu et al. method, as an accurate and simple method to predict the cell response after fractionation radiotherapy, is suggested for clinical applications. PMID- 26834522 TI - Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer - correlation with traditional prognostic factors. AB - BACKGROUND: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) play a key role in tumour invasion and metastasis. High levels of both proteolytic enzymes are associated with poor prognosis in breast cancer patients. The purpose of this study was to evaluate the correlation between traditional prognostic factors and uPA and PAI-1 expression in primary tumour of breast cancer patients. PATIENTS AND METHODS: 606 primary breast cancer patients were enrolled in the prospective study in the Department of gynaecological oncology and breast oncology at the University Medical Centre Maribor between the years 2004 and 2010. We evaluated the traditional prognostic factors (age, menopausal status, tumour size, pathohistological type, histologic grade, lymph node status, lymphovascular invasion and hormone receptor status), together with uPA and PAI-1. We used Spearman's rank correlation, Mann Whitney U test and chi(2) test for statistical analysis. RESULTS: Our findings indicate a positive correlation between uPA and tumour size (p < 0.001), grade (p < 0.001), histological type (p < 0.001), lymphovascular invasion (p = 0.01) and a negative correlation between uPA and hormone receptor status (p < 0.001). They also indicate a positive correlation between PAI-1 and tumour size (p = 0.004), grade (p < 0.001), pathohistological type (p < 0.001) and negative correlation between PAI-1 and hormone receptor status (p = 0.002). CONCLUSIONS: Our study showed a relationship between uPA and PAI-1 and traditional prognostic factors. Their role as prognostic and predictive factors remains to be further evaluated. PMID- 26834515 TI - The Current and Future Therapies for Human Osteosarcoma. AB - Osteosarcoma (OS) is the most common non-hematologic malignant tumor of bone in adults and children. As sarcomas are more common in adolescents and young adults than most other forms of cancer, there are a significant number of years of life lost secondary to these malignancies. OS is associated with a poor prognosis secondary to a high grade at presentation, resistance to chemotherapy and a propensity to metastasize to the lungs. Current OS management involves both chemotherapy and surgery. The incorporation of cytotoxic chemotherapy into therapeutic regimens escalated cure rates from <20% to current levels of 65-75%. Furthermore, limb-salvage surgery is now offered to the majority of OS patients. Despite advances in chemotherapy and surgical techniques over the past three decades, there has been stagnation in patient survival outcome improvement, especially in patients with metastatic OS. Thus, there is a critical need to identify novel and directed therapy for OS. Several Phase I trials for sarcoma therapies currently ongoing or recently completed have shown objective responses in OS. Novel drug delivery mechanisms are currently under phase II and III clinical trials. Furthermore, there is an abundance of preclinical research which holds great promise in the development of future OS-directed therapeutics. Our continuously improving knowledge of the molecular and cell-signaling pathways involved in OS will translate into more effective therapies for OS and ultimately improved patient survival. The present review will provide an overview of current therapies, ongoing clinical trials and therapeutic targets under investigation for OS. PMID- 26834524 TI - Clinical results of proton beam therapy for twenty older patients with esophageal cancer. AB - BACKGROUND: In an aging society, increasing number of older patients are diagnosed with esophageal cancer. The purpose of this study was to assess the clinical efficacy and safety of proton beam therapy for older patients with esophageal cancer. PATIENTS AND METHODS: Older patients (age: >= 65 years) newly diagnosed with esophageal cancer between January 2009 and June 2013 were enrolled in this study. All patients underwent either proton beam therapy alone or proton beam therapy with initial X-ray irradiation. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: Twenty patients were eligible for this study and all completed the treatment. The median age was 78 years (range: 65-89 years) and the median follow-up time was 26.5 months (range: 6-62 months). Seven patients had lymph node metastases and 10 had stage II/III cancer. The median dose of proton beam therapy was 72.6 Gy relative biological dose effectiveness (RBE) (range: 66-74.8 Gy [RBE]) for proton beam therapy alone and 33 Gy (RBE) (range: 30.8-39.6 Gy [RBE]; total dose range: 66.8 75.6 Gy [RBE]) for proton beam therapy with initial X-ray irradiation. The 2-year overall survival rate was 81.8% (95% confidence interval [CI]: 62.4%-100%), and the 2-year local control rate was 89.4% (95% CI: 75.5%-100%). Grade 2 or 3 toxicities occurred in some cases; however, no grade 4 or 5 toxicity was observed. CONCLUSIONS: High-dose (66-75.6 Gy [RBE]) proton beam therapy without chemotherapy was an efficacious and safe treatment for older patients with esophageal cancer. PMID- 26834523 TI - Prognostic value of some tumor markers in unresectable stage IV oropharyngeal carcinoma patients treated with concomitant radiochemotherapy. AB - BACKGROUND: The aim of the study was to investigate how the expression of tumor markers p21, p27, p53, cyclin D1, EGFR, Ki-67, and CD31 influenced the outcome of advanced inoperable oropharyngeal carcinoma patients, treated with concomitant radiochemotherapy. PATIENTS AND METHODS: The pretreatment biopsy specimens of 74 consecutive patients with inoperable stage IV oropharyngeal squamous cell carcinoma treated with concomitant radiochemotherapy were in retrospective study processed by immunochemistry for p21, p27, p53, cyclin D1, EGFR, Ki-67, and CD31. Disease-free survival (DFS) was assessed according to the expression of tumor markers. RESULTS: Patients with a high expression of p21 (>=10%), p27 (>50%), Ki 67 (>50%), CD31 (>130 vessels/mm2) and low expression of p53 (<10%), cyclin D1 (<10%) and EGFR (<10%) (favorable levels - FL) had better DFS than patients with a low expression of p21 (<10%), p27 (<=50%), Ki-67 (<=50%), CD31 (<130 vessels/mm2) and high expression of p53 (>=10%), cyclin D1 (>=10%) and EGFR (>=10%) (unfavorable levels - UL). However, statistical significance in survival between FL and UL was achieved only for p27 and cyclin D1. DFS significantly decreased with an increasing number of markers with an unfavorable level per tumor (1-4 vs. 5-7) (78% vs. 32%, respectively; p = 0.004). The number of markers per tumor with UL of expression retained prognostic significance also in multivariate analysis. CONCLUSIONS: Statistical significance in survival between FL and UL emerged only for p27 and cyclin D1. The number of markers per tumor with UL of expression was an independent prognostic factor for an adverse outcome. PMID- 26834525 TI - Cutaneous melanoma frequencies and seasonal trend in 20 years of observation of a population characterised by excessive sun exposure. AB - BACKGROUND: Cutaneous melanoma is an aggressive form of skin cancer. It has become an increasingly common neoplasm in the most developed countries, especially among individuals of European origin. PATIENTS AND METHODS: Anonymous data of patients with cutaneous melanoma were collected from the diagnostic database of the University Hospital of Trieste from 1 January 1990 to 10 December 2013. Our study is based on a population which was constant over the period of observation; it was also well-defined and characterised by unrestrained sun exposure. RESULTS: The number of cutaneous melanomas increased during the period of observation with a seasonality trend and gender related differences both for anatomical sites distribution and stage of the disease. Moreover, 6% of our cohort developed multiple melanomas. CONCLUSIONS: In a well-defined population devoted to excessive sun exposure the frequencies of skin melanomas roughly doubled from 1990 to 2013 following a seasonal trend. In that population, prevention efforts according to gender specific risk behaviour, as well as follow up programmes both for evaluation of metastatic spreading and for early diagnosis of additional skin melanomas, are crucial due to gender specific differences and to the occurrence of multiple melanomas. PMID- 26834526 TI - Release of growth factors after mechanical and chemical pleurodesis for treatment of malignant pleural effusion: a randomized control study. AB - BACKGROUND: Growth factors are key inducers of fibrosis but can also mediate inflammatory responses resulting in increasing pleural effusion and acute respiratory distress syndrome. The primary aim of the study was to analyse growth factors release after performing chemical and mechanical pleurodesis in the first 48 hours at the patients with malignant pleural effusion. The secondary endpoints were to evaluate the effectiveness of the both pleurodeses, symptoms release and the quality of life of patients after the treatment. PATIENTS AND METHODS: A prospective randomized study included 36 consecutive female patients with breast carcinoma and malignant pleural effusion in an intention-to-treat analysis. We treated 18 patients by means of thoracoscopic mechanical pleurodesis and 18 patients by chemical pleurodesis with talcum applied over a chest tube. We gathered the pleural fluid and serum samples in the following 48 hours under a dedicated protocol and tested them for growth factors levels. A quality of life and visual analogue pain score surveys were also performed. RESULTS: Median measured serum vascular endothelial growth factor (VEGF) level after chemical pleurodesis was 930.68 pg/ml (95% CI: 388.22-4656.65) and after mechanical pleurodesis 808.54 pg/ml. (95% CI: 463.20-1235.13) (p = 0.103). Median pleural levels of transforming growth factor (TGF) beta1 were higher after performing mechanical pleurodesis (4814.00 pg/ml [95% CI: 2726.51-7292.94]) when compared to those after performing chemical pleurodesis (1976.50 pg/ml [95% CI: 1659.82 5136.26]) (p = 0.078). We observed similar results for fibroblast growth factor (FGF) beta; the serum level was higher after mechanical pleurodesis (30.45 pg/ml [95% CI: 20.40-59.42]), compared to those after chemical pleurodesis (13.39 pg/ml [95% CI: 5.04 - 74.60]) (p = 0.076). Mechanical pleurodesis was equally effective as chemical pleurodesis in terms of hospital stay, pleural effusion re accumulation, requiring of additional thoracentesis, median overall survival, but, it shortened the mean thoracic drainage duration (p = 0.030) and resulted in a higher symptoms release and in a better quality of life (p = 0.047). CONCLUSIONS: We recorded an increase in serum VEGF levels after chemical pleurodesis, however on the contrary, an increase in the pleural fluid level of TGFbeta1 and FGFbeta] after mechanical pleurodesis with respect to compared group. Although the differences did not reach statistical significance, VEGF, TGFbeta1 and FGFbeta remain the most interesting parameters for future research. Considering the mechanisms of growth factors action, we conclude that in our study group mechanical pleurodesis might be more efficient in terms of growth factors release, thoracic drainage duration and resulted in a higher symptoms release and in a better quality of life than chemical pleurodesis. PMID- 26834528 TI - Impact of comorbidity on the outcome in men with advanced prostate cancer treated with docetaxel. AB - BACKGROUND: Men with metastatic castrate-resistant prostate cancer (mCRPC) may not receive docetaxel in everyday clinical practice due to comorbidities. Here we explore the impact of comorbidity on outcome in men with mCRPC treated with docetaxel in a population-based outcome study. METHODS: Men with mCRPC treated with docetaxel at the Institute of Oncology Ljubljana between 2005 and 2012 were eligible. Comorbidity was assessed by the age-adjusted Charlson comorbidity index (aa-CCI) and adult comorbidity evaluation (ACE-27) index. Hospital admissions due to the toxicity and deaths during treatment with docetaxel were used as a measure of tolerability. Association between comorbidity and overall survival (OS) was tested using the Cox proportional hazards analysis. RESULTS: Two hundred and eight men were treated with docetaxel. No, mild, moderate and severe comorbidity was present in 2%, 32%, 53% and 13% using aa-CCI and in 27%, 35%, 29% and 8% when assessed by ACE-27. A substantial dose reduction of docetaxel occurred more often in men with moderate or severe comorbidity as compared to those with no or mild comorbidity. At all comorbidity levels about one-third of men required hospitalization or died during treatment with docetaxel. In univariate analysis a higher level of comorbidity was not associated with worse OS (aa-CCI HR 0.99; [95% CI 0.87-1.13], p = 0.93; ACE-27: HR 0.96; [95% CI 0.79-1.17], p = 0.69). CONCLUSIONS: Men with mCRPC, who have comorbidities may benefit from treatment with docetaxel. PMID- 26834527 TI - Giant solitary fibrous tumour of the pleura. Case report and review of the literature. AB - BACKGROUND: Solitary fibrous tumours of the pleura (SFTP) are rare tumours. They are mostly benign. Only around 12% of them are malign ant. In the initial stage they are mostly asymptomatic and by growing they cause chest pain, irritating cough and dyspnoea on account of the pressure created on the surrounding structures. Rare giant tumours have compression symptoms on the mediastinal structures. The condition requires tiered diagnostic radiology. Preoperative biopsy is not successful in most cases. The therapy of choice is radical surgical tumour removal. Malignant or non-radically removed benign solitary fibrous tumours of the pleura additionally require neoadjuvant therapy. CASE REPORT: A 68 year old patient was hospitalized for giant solitary fibrous tumour of the pleura in the right pleural cavity. With its expansive growth the tumour caused the shift of the mediastinum by compressing the lower vena cava, right cardiac auricle as well as the intermediate and lower lobe bronchus. Due to cardiac inflow obstruction and right lung collapse, the patient's life was endangered with signs of cardio-respiratory failure. After preoperative diagnostic radiology, the tumour was surgically removed. Postoperatively, the patient's condition improved. No disease recurrence was diagnosed after a year. CONCLUSIONS: Giant solitary fibrous tumour of the pleura may cause serious and life-threatening conditions by causing compression of the pleural cavity with its expansive growth. Early diagnosis of the condition enables less aggressive as well as video-assisted thoracic surgery in patients with significantly better state of health. Large tumour surgeries in cardio-respiratory affected patients are highly risk-associated procedures. PMID- 26834529 TI - Clinical impact of post-progression survival on overall survival in patients with limited-stage disease small cell lung cancer after first-line chemoradiotherapy. AB - BACKGROUND: The effects of first-line chemoradiotherapy on overall survival (OS) may be confounded by subsequent lines of therapy in patients with limited-stage disease small cell lung cancer (LD-SCLC). Therefore, we aimed to determine the relationships between progression-free survival (PFS), post-progression survival (PPS) and OS after first-line chemoradiotherapy in LD-SCLC patients. PATIENTS AND METHODS: We retrospectively analyzed 71 LD-SCLC patients with performance status (PS) 0-2 who received first-line chemoradiotherapy and had disease recurrence between September 2002 and March 2013 at Shizuoka Cancer Center (Shizuoka, Japan). We determined the correlation between PFS and OS and between PPS and OS at the individual level. In addition, we performed univariate and multivariate analyses to identify significant prognostic factors of PPS. RESULTS: OS is more strongly correlated with PPS (Spearman's r = 0.86, R (2) = 0.72, p < 0.05) than PFS (Spearman's r = 0.46, R (2) = 0.38, p < 0.05). In addition, the response to second-line treatments, the presence of distant metastases at recurrence and the number of additional regimens after first-line chemoradiotherapy were significant independent prognostic factors for PPS. CONCLUSIONS: PPS has more impact on OS than PFS in recurrent LD-SCLC patients with good PS at beginning of the treatment. Moreover, treatments administered after first-line chemoradiotherapy may affect their OS. However, larger multicenter studies are needed to validate these findings. PMID- 26834530 TI - Ankle-brachial index and eicosapentaenoic acid/arachidonic acid ratio in smokers with type 2 diabetes mellitus. AB - BACKGROUND: The ankle-brachial index (ABI) is an indicator of peripheral arterial damage and a low (ABI <= 1.0) or borderline (ABI = 1.00-1.09) value is associated with risk of cardiovascular disease events. A low ratio of serum eicosapentaenoic acid to arachidonic acid (EPA/AA) is also a risk factor for cardiovascular disease events. This study examined associations between the ABI and the EPA/AA ratio in smokers and non-smokers with type 2 diabetes mellitus (T2DM). FINDINGS: Blood data including EPA, AA, and ABI were measured in smokers and non-smokers with T2DM enrolled at Jichi Medical University (n = 116, male 86 %, mean age 59 yr). The patients were classified into two groups according to their ABI level: <1.1 (low to borderline) or >=1.1 (high). The EPA/AA ratio in smoking patients with ABI < 1.1 (n = 26; EPA/AA = 0.25) was significantly lower than in those with ABI >= 1.1 (n = 32; EPA/AA = 0.34; p = 0.03), but was not significantly different in non-smoking patients. The EPA/AA ratio was independently, significantly, and positively correlated with the ABI level (beta = 0.41; p < 0.01) after adjusting for multiple variables only in smoking patients with T2DM. CONCLUSIONS: The EPA/AA ratio may be associated with subclinical peripheral arterial damage in smokers with T2DM. Further studies are warranted. PMID- 26834531 TI - It's All in How You Think About It: Construal Level and the Iowa Gambling Task. AB - Recent research has identified a number of factors that can influence performance on the Iowa Gambling Task (IGT) when it is used in clinical or research settings. The current studies examine the effects of construal level theory (CLT) on the IGT. Study 1 suggests that when primed with a high construal mindset (i.e., thinking abstractly vs. concretely), individuals learned to avoid Deck A more than those primed with a low construal mindset. Study 2 suggests that when construal level is manipulated through psychological distance (i.e., selecting for a close vs. distant friend), individuals in a high construal mindset instead showed a preference for Deck A compared to individuals in a low construal mindset or a control group. Taken together, these studies suggest that IGT performance is impacted by the manner in which one construes the task. Implications for decision making research and use of the IGT as a clinical and research instrument are discussed. PMID- 26834533 TI - When the Single Matters more than the Group (II): Addressing the Problem of High False Positive Rates in Single Case Voxel Based Morphometry Using Non-parametric Statistics. AB - In recent years, an increasing number of studies have used Voxel Based Morphometry (VBM) to compare a single patient with a psychiatric or neurological condition of interest against a group of healthy controls. However, the validity of this approach critically relies on the assumption that the single patient is drawn from a hypothetical population with a normal distribution and variance equal to that of the control group. In a previous investigation, we demonstrated that family-wise false positive error rate (i.e., the proportion of statistical comparisons yielding at least one false positive) in single case VBM are much higher than expected (Scarpazza et al., 2013). Here, we examine whether the use of non-parametric statistics, which does not rely on the assumptions of normal distribution and equal variance, would enable the investigation of single subjects with good control of false positive risk. We empirically estimated false positive rates (FPRs) in single case non-parametric VBM, by performing 400 statistical comparisons between a single disease-free individual and a group of 100 disease-free controls. The impact of smoothing (4, 8, and 12 mm) and type of pre-processing (Modulated, Unmodulated) was also examined, as these factors have been found to influence FPRs in previous investigations using parametric statistics. The 400 statistical comparisons were repeated using two independent, freely available data sets in order to maximize the generalizability of the results. We found that the family-wise error rate was 5% for increases and 3.6% for decreases in one data set; and 5.6% for increases and 6.3% for decreases in the other data set (5% nominal). Further, these results were not dependent on the level of smoothing and modulation. Therefore, the present study provides empirical evidence that single case VBM studies with non-parametric statistics are not susceptible to high false positive rates. The critical implication of this finding is that VBM can be used to characterize neuroanatomical alterations in individual subjects as long as non-parametric statistics are employed. PMID- 26834532 TI - The Metamorphic Nature of the Tau Protein: Dynamic Flexibility Comes at a Cost. AB - Accumulation of the microtubule associated protein tau occurs in several neurodegenerative diseases including Alzheimer's disease (AD). The tau protein is intrinsically disordered, giving it unique structural properties that can be dynamically altered by post-translational modifications such as phosphorylation and cleavage. Over the last decade, technological advances in nuclear magnetic resonance (NMR) spectroscopy and structural modeling have permitted more in-depth insights into the nature of tau. These studies have helped elucidate how metamorphism of tau makes it ideally suited for dynamic microtubule regulation, but how it also facilitates tau self-assembly, oligomerization, and neurotoxicity. This review will focus on how the distinct structure of tau governs its function, accumulation, and toxicity as well as how other cellular factors such as molecular chaperones control these processes. PMID- 26834534 TI - Perceptual Correlates of Turkish Word Stress and Their Contribution to Automatic Lexical Access: Evidence from Early ERP Components. AB - Perceptual correlates of Turkish word stress and their contribution to lexical access were studied using the mismatch negativity (MMN) component in event related potentials (ERPs). The MMN was expected to indicate if segmentally identical Turkish words were distinguished on the sole basis of prosodic features such as fundamental frequency (f 0), spectral emphasis (SE), and duration. The salience of these features in lexical access was expected to be reflected in the amplitude of MMN responses. In a multi-deviant oddball paradigm, neural responses to changes in f 0, SE, and duration individually, as well as to all three features combined, were recorded for words and pseudowords presented to 14 native speakers of Turkish. The word and pseudoword contrast was used to differentiate language-related effects from acoustic-change effects on the neural responses. First and in line with previous findings, the overall MMN was maximal over frontal and central scalp locations. Second, changes in prosodic features elicited neural responses both in words and pseudowords, confirming the brain's automatic response to any change in auditory input. However, there were processing differences between the prosodic features, most significantly in f 0: While f 0 manipulation elicited a slightly right-lateralized frontally-maximal MMN in words, it elicited a frontal P3a in pseudowords. Considering that P3a is associated with involuntary allocation of attention to salient changes, the manipulations of f 0 in the absence of lexical processing lead to an intentional evaluation of pitch change. f 0 is therefore claimed to be lexically specified in Turkish. Rather than combined features, individual prosodic features differentiate language-related effects from acoustic-change effects. The present study confirms that segmentally identical words can be distinguished on the basis of prosodic information alone, and establishes the salience of f 0 in lexical access. PMID- 26834535 TI - Resonant Cholinergic Dynamics in Cognitive and Motor Decision-Making: Attention, Category Learning, and Choice in Neocortex, Superior Colliculus, and Optic Tectum. AB - Freely behaving organisms need to rapidly calibrate their perceptual, cognitive, and motor decisions based on continuously changing environmental conditions. These plastic changes include sharpening or broadening of cognitive and motor attention and learning to match the behavioral demands that are imposed by changing environmental statistics. This article proposes that a shared circuit design for such flexible decision-making is used in specific cognitive and motor circuits, and that both types of circuits use acetylcholine to modulate choice selectivity. Such task-sensitive control is proposed to control thalamocortical choice of the critical features that are cognitively attended and that are incorporated through learning into prototypes of visual recognition categories. A cholinergically-modulated process of vigilance control determines if a recognition category and its attended features are abstract (low vigilance) or concrete (high vigilance). Homologous neural mechanisms of cholinergic modulation are proposed to focus attention and learn a multimodal map within the deeper layers of superior colliculus. This map enables visual, auditory, and planned movement commands to compete for attention, leading to selection of a winning position that controls where the next saccadic eye movement will go. Such map learning may be viewed as a kind of attentive motor category learning. The article hereby explicates a link between attention, learning, and cholinergic modulation during decision making within both cognitive and motor systems. Homologs between the mammalian superior colliculus and the avian optic tectum lead to predictions about how multimodal map learning may occur in the mammalian and avian brain and how such learning may be modulated by acetycholine. PMID- 26834538 TI - Mimicking Collective Firing Patterns of Hundreds of Connected Neurons using a Single-Neuron Experiment. AB - The experimental study of neural networks requires simultaneous measurements of a massive number of neurons, while monitoring properties of the connectivity, synaptic strengths and delays. Current technological barriers make such a mission unachievable. In addition, as a result of the enormous number of required measurements, the estimated network parameters would differ from the original ones. Here we present a versatile experimental technique, which enables the study of recurrent neural networks activity while being capable of dictating the network connectivity and synaptic strengths. This method is based on the observation that the response of neurons depends solely on their recent stimulations, a short-term memory. It allows a long-term scheme of stimulation and recording of a single neuron, to mimic simultaneous activity measurements of neurons in a recurrent network. Utilization of this technique demonstrates the spontaneous emergence of cooperative synchronous oscillations, in particular the coexistence of fast gamma and slow delta oscillations, and opens the horizon for the experimental study of other cooperative phenomena within large-scale neural networks. PMID- 26834536 TI - Evaluation of Models of Parkinson's Disease. AB - Parkinson's disease is one of the most common neurodegenerative diseases. Animal models have contributed a large part to our understanding and therapeutics developed for treatment of PD. There are several more exhaustive reviews of literature that provide the initiated insights into the specific models; however a novel synthesis of the basic advantages and disadvantages of different models is much needed. Here we compare both neurotoxin based and genetic models while suggesting some novel avenues in PD modeling. We also highlight the problems faced and promises of all the mammalian models with the hope of providing a framework for comparison of various systems. PMID- 26834537 TI - Altered Expression Patterns of Inflammation-Associated and Trophic Molecules in Substantia Nigra and Striatum Brain Samples from Parkinson's Disease, Incidental Lewy Body Disease and Normal Control Cases. AB - Evidence of inflammation has been consistently associated with pathology in Parkinson's disease (PD)-affected brains, and has been suggested as a causative factor. Dopaminergic neurons in the substantia nigra (SN) pars compacta, whose loss results in the clinical symptoms associated with PD, are particularly susceptible to inflammatory damage and oxidative stress. Inflammation in the striatum, where SN dopaminergic neurons project, is also a feature of PD brains. It is not known whether inflammatory changes occur first in striatum or SN. Many animal models of PD have implicated certain inflammatory molecules with dopaminergic cell neuronal loss; however, there have been few studies to validate these findings by measuring the levels of these and other inflammatory factors in human PD brain samples. This study also included samples from incidental Lewy body disease (ILBD) cases, since ILBD is considered a non-symptomatic precursor to PD, with subjects having significant loss of tyrosine hydroxylase-producing neurons. We hypothesized that there may be a progressive change in key inflammatory factors in ILBD samples intermediate between neurologically normal and PD. To address this, we used a quantitative antibody-array platform (Raybiotech-Quantibody arrays) to measure the levels of 160 different inflammation-associated cytokines, chemokines, growth factors, and related molecules in extracts of SN and striatum from clinically and neuropathologically characterized PD, ILBD, and normal control cases. Patterns of changes in inflammation and related molecules were distinctly different between SN and striatum. Our results showed significantly different levels of interleukin (IL) 5, IL-15, monokine induced by gamma interferon, and IL-6 soluble receptor in SN between disease groups. A different panel of 13 proteins with significant changes in striatum, with IL-15 as the common feature, was identified. Although the ability to detect some proteins was limited by sensitivity, patterns of expression indicated involvement of certain T-cell cytokines, vascular changes, and loss of certain growth factors, with disease progression. The results demonstrate the feasibility of profiling inflammatory molecules using diseased human brain samples, and have provided additional targets to validate in relation to PD pathology. PMID- 26834539 TI - A Rapid, Semi-Quantitative Assay to Screen for Modulators of Alpha-Synuclein Oligomerization Ex vivo. AB - Alpha synuclein (alphasyn) aggregates are associated with the pathogenesis of Parkinson's disease and others related disorders. Although modulation of alphasyn aggregation is an attractive therapeutic target, new powerful methodologies are desperately needed to facilitate in vivo screening of novel therapeutics. Here, we describe an in vivo rodent model with the unique ability to rapidly track alphasyn-alphasyn interactions and thus oligomerization using a bioluminescent protein complementation strategy that monitors spatial and temporal alphasyn oligomerization ex vivo. We find that alphasyn forms oligomers in vivo as early as 1 week after stereotactic AAV injection into rat substantia nigra. Strikingly, although abundant alphasyn expression is also detected in striatum at 1 week, no alphasyn oligomers are detected at this time point. By 4 weeks, oligomerization of alphasyn is detected in both striatum and substantia nigra homogenates. Moreover, in a proof-of-principle experiment, the effect of a previously described Hsp90 inhibitor known to prevent alphasyn oligomer formation, demonstrates the utility of this rapid and sensitive animal model to monitor alphasyn oligomerization status in the rat brain. PMID- 26834540 TI - Reduced Oblique Effect in Children with Autism Spectrum Disorders (ASD). AB - People are very precise in the discrimination of a line orientation relative to the cardinal (vertical and horizontal) axes, while their orientation discrimination sensitivity along the oblique axes is less refined. This difference in discrimination sensitivity along cardinal and oblique axes is called the "oblique effect." Given that the oblique effect is a basic feature of visual processing with an early developmental origin, its investigation in children with Autism Spectrum Disorder (ASD) may shed light on the nature of visual sensory abnormalities frequently reported in this population. We examined line orientation sensitivity along oblique and vertical axes in a sample of 26 boys with ASD (IQ > 68) and 38 typically developing (TD) boys aged 7-15 years, as well as in a subsample of carefully IQ-matched ASD and TD participants. Children were asked to detect the direction of tilt of a high-contrast black-and-white grating relative to vertical (90 degrees ) or oblique (45 degrees ) templates. The oblique effect was reduced in children with ASD as compared to TD participants, irrespective of their IQ. This reduction was due to poor orientation sensitivity along the vertical axis in ASD children, while their ability to discriminate line orientation along the oblique axis was unaffected. We speculate that this deficit in sensitivity to vertical orientation may reflect disrupted mechanisms of early experience-dependent learning that takes place during the critical period for orientation selectivity. PMID- 26834543 TI - Corrigendum: A dynamical model improves reconstruction of handwriting from multichannel electromyographic recordings. AB - [This corrects the article on p. 389 in vol. 9, PMID: 26578856.]. PMID- 26834542 TI - NeuroFlow: A General Purpose Spiking Neural Network Simulation Platform using Customizable Processors. AB - NeuroFlow is a scalable spiking neural network simulation platform for off-the shelf high performance computing systems using customizable hardware processors such as Field-Programmable Gate Arrays (FPGAs). Unlike multi-core processors and application-specific integrated circuits, the processor architecture of NeuroFlow can be redesigned and reconfigured to suit a particular simulation to deliver optimized performance, such as the degree of parallelism to employ. The compilation process supports using PyNN, a simulator-independent neural network description language, to configure the processor. NeuroFlow supports a number of commonly used current or conductance based neuronal models such as integrate-and fire and Izhikevich models, and the spike-timing-dependent plasticity (STDP) rule for learning. A 6-FPGA system can simulate a network of up to ~600,000 neurons and can achieve a real-time performance of 400,000 neurons. Using one FPGA, NeuroFlow delivers a speedup of up to 33.6 times the speed of an 8-core processor, or 2.83 times the speed of GPU-based platforms. With high flexibility and throughput, NeuroFlow provides a viable environment for large-scale neural network simulation. PMID- 26834541 TI - Non-invasive Brain Stimulation and Auditory Verbal Hallucinations: New Techniques and Future Directions. AB - Auditory verbal hallucinations (AVHs) are the experience of hearing a voice in the absence of any speaker. Results from recent attempts to treat AVHs with neurostimulation (rTMS or tDCS) to the left temporoparietal junction have not been conclusive, but suggest that it may be a promising treatment option for some individuals. Some evidence suggests that the therapeutic effect of neurostimulation on AVHs may result from modulation of cortical areas involved in the ability to monitor the source of self-generated information. Here, we provide a brief overview of cognitive models and neurostimulation paradigms associated with treatment of AVHs, and discuss techniques that could be explored in the future to improve the efficacy of treatment, including alternating current and random noise stimulation. Technical issues surrounding the use of neurostimulation as a treatment option are discussed (including methods to localize the targeted cortical area, and the state-dependent effects of brain stimulation), as are issues surrounding the acceptability of neurostimulation for adolescent populations and individuals who experience qualitatively different types of AVH. PMID- 26834544 TI - Tractography Activation Patterns in Dorsolateral Prefrontal Cortex Suggest Better Clinical Responses in OCD DBS. AB - BACKGROUND: Medication resistant obsessive-compulsive disorder (OCD) patients can be successfully treated with Deep Brain Stimulation (DBS) which targets the anterior limb of the internal capsule (ALIC) and the nucleus accumbens (NA). Growing evidence suggests that in patients who respond to DBS, axonal fiber bundles surrounding the electrode are activated, but it is currently unknown which discrete pathways are critical for optimal benefit. Our aim was to identify axonal pathways mediating clinical effects of ALIC-NA DBS. METHODS: We created computational models of ALIC-NA DBS to simulate the activation of fiber tracts and to identify connected cerebral regions. The pattern of activated axons and their cortical targets was investigated in six OCD patients who underwent ALIC-NA DBS. RESULTS: Modulation of the right anterior middle frontal gyrus (dorsolateral prefrontal cortex) was associated with an excellent response. In contrast, non responders showed high activation in the orbital part of the right inferior frontal gyrus (lateral orbitofrontal cortex/anterior ventrolateral prefrontal cortex). Factor analysis followed by step-wise linear regression indicated that YBOCS improvement was inversely associated with factors that were predominantly determined by gray matter activation results. DISCUSSION: Our findings support the hypothesis that optimal therapeutic results are associated with the activation of distinct fiber pathways. This suggests that in DBS for OCD, focused stimulation of specific fiber pathways, which would allow for stimulation with lower amplitudes, may be superior to activation of a wide array of pathways, typically associated with higher stimulation amplitudes. PMID- 26834545 TI - In silico Therapeutics for Neurogenic Hypertension and Vasovagal Syncope. AB - Neurocardiovascular diseases (NCVD) are the leading cause of death in the developed world and will remain so till 2020. In these diseases the pathologically changed nervous control of cardiovascular system has the central role. The actual NCV syndromes are neurogenic hypertension, representing the sympathetically mediated disorder, and vasovagal syncope, which is the vagally mediated disorders. Vasovagal syncope, the disease far from its etiological treatment, could benefit from recruiting and application of antimuscarinic drugs used in other parasympathetic disorders. The informational spectrum method (ISM), a method widely applied for the characterization of protein-protein interactions in the field of immunology, endocrinology and anti HIV drug discovery, was applied for the first time in the analysis of neurogenic hypertension and vasovagal syncope therapeutic targets. In silico analysis revealed the potential involvement of apelin in neurogenic hypertension. Applying the EIIP/ISM bioinformatics concept in investigation of drugs for treatment of vasovagal syncope suggests that 78% of tested antimuscarinic drugs could have anti vasovagal syncope effect. The presented results confirm that ISM is a promissing method for investigation of molecular mechanisms underlying pathophysiological proceses of NCV syndromes and discovery of therapeutics targets for their treatment. PMID- 26834546 TI - PEDOT:PSS Interfaces Support the Development of Neuronal Synaptic Networks with Reduced Neuroglia Response In vitro. AB - The design of electrodes based on conductive polymers in brain-machine interface technology offers the opportunity to exploit variably manufactured materials to reduce gliosis, indeed the most common brain response to chronically implanted neural electrodes. In fact, the use of conductive polymers, finely tailored in their physical-chemical properties, might result in electrodes with improved adaptability to the brain tissue and increased charge-transfer efficiency. Here we interfaced poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) ( PEDOT: PSS) doped with different amounts of ethylene glycol (EG) with rat hippocampal primary cultures grown for 3 weeks on these synthetic substrates. We used immunofluorescence and scanning electron microscopy (SEM) combined to single cell electrophysiology to assess the biocompatibility of PEDOT: PSS in terms of neuronal growth and synapse formation. We investigated neuronal morphology, density and electrical activity. We reported the novel observation that opposite to neurons, glial cell density was progressively reduced, hinting at the ability of this material to down regulate glial reaction. Thus, PEDOT: PSS is an attractive candidate for the design of new implantable electrodes, controlling the extent of glial reactivity without affecting neuronal viability and function. PMID- 26834547 TI - Neuromorphic Event-Based 3D Pose Estimation. AB - Pose estimation is a fundamental step in many artificial vision tasks. It consists of estimating the 3D pose of an object with respect to a camera from the object's 2D projection. Current state of the art implementations operate on images. These implementations are computationally expensive, especially for real time applications. Scenes with fast dynamics exceeding 30-60 Hz can rarely be processed in real-time using conventional hardware. This paper presents a new method for event-based 3D object pose estimation, making full use of the high temporal resolution (1 MUs) of asynchronous visual events output from a single neuromorphic camera. Given an initial estimate of the pose, each incoming event is used to update the pose by combining both 3D and 2D criteria. We show that the asynchronous high temporal resolution of the neuromorphic camera allows us to solve the problem in an incremental manner, achieving real-time performance at an update rate of several hundreds kHz on a conventional laptop. We show that the high temporal resolution of neuromorphic cameras is a key feature for performing accurate pose estimation. Experiments are provided showing the performance of the algorithm on real data, including fast moving objects, occlusions, and cases where the neuromorphic camera and the object are both in motion. PMID- 26834548 TI - Evaluating Alzheimer's Disease Progression by Modeling Crosstalk Network Disruption. AB - Abeta, tau, and P-tau have been widely accepted as reliable markers for Alzheimer's disease (AD). The crosstalk between these markers forms a complex network. AD may induce the integral variation and disruption of the network. The aim of this study was to develop a novel mathematic model based on a simplified crosstalk network to evaluate the disease progression of AD. The integral variation of the network is measured by three integral disruption parameters. The robustness of network is evaluated by network disruption probability. Presented results show that network disruption probability has a good linear relationship with Mini Mental State Examination (MMSE). The proposed model combined with Support vector machine (SVM) achieves a relative high 10-fold cross-validated performance in classification of AD vs. normal and mild cognitive impairment (MCI) vs. normal (95% accuracy, 95% sensitivity, 95% specificity for AD vs. normal; 90% accuracy, 94% sensitivity, 83% specificity for MCI vs. normal). This research evaluates the progression of AD and facilitates AD early diagnosis. PMID- 26834549 TI - Exposure of BALB/c Mice to Diesel Engine Exhaust Origin Secondary Organic Aerosol (DE-SOA) during the Developmental Stages Impairs the Social Behavior in Adult Life of the Males. AB - Secondary organic aerosol (SOA) is a component of particulate matter (PM) 2.5 and formed in the atmosphere by oxidation of volatile organic compounds. Recently, we have reported that inhalation exposure to diesel engine exhaust (DE) originated SOA (DE-SOA) affect novel object recognition ability and impair maternal behavior in adult mice. However, it is not clear whether early life exposure to SOA during the developmental stages affect social behavior in adult life or not. In the present study, to investigate the effects of early life exposure to DE-SOA during the gestational and lactation stages on the social behavior in the adult life, BALB/c mice were exposed to clean air (control), DE, DE-SOA and gas without any PM in the inhalation chambers from gestational day 14 to postnatal day 21 for 5 h a day and 5 days per week. Then adult mice were examined for changes in their social behavior at the age of 13 week by a sociability and social novelty preference, social interaction with a juvenile mouse and light-dark transition test, hypothalamic mRNA expression levels of social behavior-related genes, estrogen receptor-alpha and oxytocin receptor as well as of the oxidative stress marker gene, heme oxygenase (HO)-1 by real-time RT-PCR method. In addition, hypothalamic level of neuronal excitatory marker, glutamate was determined by ELISA method. We observed that sociability and social novelty preference as well as social interaction were remarkably impaired, expression levels of estrogen receptor-alpha, oxytocin receptor mRNAs were significantly decreased, expression levels of HO-1 mRNAs and glutamate levels were significantly increased in adult male mice exposed to DE-SOA compared to the control ones. Findings of this study indicate early life exposure of BALB/c mice to DE-SOA may affect their late-onset hypothalamic expression of social behavior related genes, trigger neurotoxicity and impair social behavior in the males. PMID- 26834551 TI - Factors of Influence on the Performance of a Short-Latency Non-Invasive Brain Switch: Evidence in Healthy Individuals and Implication for Motor Function Rehabilitation. AB - Brain-computer interfacing (BCI) has recently been applied as a rehabilitation approach for patients with motor disorders, such as stroke. In these closed-loop applications, a brain switch detects the motor intention from brain signals, e.g., scalp EEG, and triggers a neuroprosthetic device, either to deliver sensory feedback or to mimic real movements, thus re-establishing the compromised sensory motor control loop and promoting neural plasticity. In this context, single trial detection of motor intention with short latency is a prerequisite. The performance of the event detection from EEG recordings is mainly determined by three factors: the type of motor imagery (e.g., repetitive, ballistic), the frequency band (or signal modality) used for discrimination (e.g., alpha, beta, gamma, and MRCP, i.e., movement-related cortical potential), and the processing technique (e.g., time-series analysis, sub-band power estimation). In this study, we investigated single trial EEG traces during movement imagination on healthy individuals, and provided a comprehensive analysis of the performance of a short latency brain switch when varying these three factors. The morphological investigation showed a cross-subject consistency of a prolonged negative phase in MRCP, and a delayed beta rebound in sensory-motor rhythms during repetitive tasks. The detection performance had the greatest accuracy when using ballistic MRCP with time-series analysis. In this case, the true positive rate (TPR) was ~70% for a detection latency of ~200 ms. The results presented here are of practical relevance for designing BCI systems for motor function rehabilitation. PMID- 26834552 TI - Thermal Regulation of the Brain-An Anatomical and Physiological Review for Clinical Neuroscientists. AB - Humans, like all mammals and birds, maintain a near constant core body temperature of 36-37.5 degrees C over a broad range of environmental conditions and are thus referred to as endotherms. The evolution of the brain and its supporting structures in mammals and birds coincided with this development of endothermy. Despite the recognition that a more evolved and complicated brain with all of its temperature-dependent cerebral circuitry and neuronal processes would require more sophisticated thermal control mechanisms, the current understanding of brain temperature regulation remains limited. To optimize the development and maintenance of the brain in health and to accelerate its healing and restoration in illness, focused, and committed efforts are much needed to advance the fundamental understanding of brain temperature. To effectively study and examine brain temperature and its regulation, we must first understand relevant anatomical and physiological properties of thermoregulation in the head neck regions. PMID- 26834553 TI - Missense Mutation R338W in ARHGEF9 in a Family with X-linked Intellectual Disability with Variable Macrocephaly and Macro-Orchidism. AB - Non-syndromal X-linked intellectual disability (NS-XLID) represents a broad group of clinical disorders in which ID is the only clinically consistent manifestation. Although in many cases either chromosomal linkage data or knowledge of the >100 existing XLID genes has assisted mutation discovery, the underlying cause of disease remains unresolved in many families. We report the resolution of a large family (K8010) with NS-XLID, with variable macrocephaly and macro-orchidism. Although a previous linkage study had mapped the locus to Xq12 q21, this region contained too many candidate genes to be analyzed using conventional approaches. However, X-chromosome exome sequencing, bioinformatics analysis and segregation analysis revealed a novel missense mutation (c.1012C>T; p.R338W) in ARHGEF9. This gene encodes collybistin (CB), a neuronal GDP-GTP exchange factor previously implicated in several cases of XLID, as well as clustering of gephyrin and GABAA receptors at inhibitory synapses. Molecular modeling of the CB R338W substitution revealed that this change results in the substitution of a long electropositive side-chain with a large non-charged hydrophobic side-chain. The R338W change is predicted to result in clashes with adjacent amino acids (K363 and N335) and disruption of electrostatic potential and local folding of the PH domain, which is known to bind phosphatidylinositol-3 phosphate (PI3P/PtdIns-3-P). Consistent with this finding, functional assays revealed that recombinant CB CB2SH3- (R338W) was deficient in PI3P binding and was not able to translocate EGFP-gephyrin to submembrane microaggregates in an in vitro clustering assay. Taken together, these results suggest that the R338W mutation in ARHGEF9 is the underlying cause of NS-XLID in this family. PMID- 26834550 TI - The Ever-Changing Morphology of Hippocampal Granule Neurons in Physiology and Pathology. AB - Newborn neurons are continuously added to the hippocampal dentate gyrus throughout adulthood. In this review, we analyze the maturational stages that newborn granule neurons go through, with a focus on their unique morphological features during each stage under both physiological and pathological circumstances. In addition, the influence of deleterious (such as schizophrenia, stress, Alzheimer's disease, seizures, stroke, inflammation, dietary deficiencies, or the consumption of drugs of abuse or toxic substances) and neuroprotective (physical exercise and environmental enrichment) stimuli on the maturation of these cells will be examined. Finally, the regulation of this process by proteins involved in neurodegenerative and neurological disorders such as Glycogen synthase kinase 3beta, Disrupted in Schizophrenia 1 (DISC-1), Glucocorticoid receptor, pro-inflammatory mediators, Presenilin-1, Amyloid precursor protein, Cyclin-dependent kinase 5 (CDK5), among others, will be evaluated. Given the recently acquired relevance of the dendritic branch as a functional synaptic unit required for memory storage, a full understanding of the morphological alterations observed in newborn neurons may have important consequences for the prevention and treatment of the cognitive and affective alterations that evolve in conjunction with impaired adult hippocampal neurogenesis. PMID- 26834554 TI - Sugar Consumption Produces Effects Similar to Early Life Stress Exposure on Hippocampal Markers of Neurogenesis and Stress Response. AB - Adverse early life experience is a known risk factor for psychiatric disorders. It is also known that stress influences food preference. We were interested in exploring whether the choice of diet following early life stress exerts long lasting molecular changes in the brain, particularly the hippocampus, a region critically involved in stress regulation and behavioral outcomes. Here, we examined the impact of early life stress induced by limited nesting material (LN) and chronic sucrose availability post-weaning on an array of hippocampal genes related to plasticity, neurogenesis, stress and inflammatory responses and mitochondrial biogenesis. To examine mechanisms underlying the impact of LN and sugar intake on hippocampal gene expression, we investigated the role of DNA methylation. As females are more likely to experience adverse life events, we studied female Sprague-Dawley rats. After mating LN was imposed from days 2 to 9 postpartum. From 3 to 15 weeks of age, female Control and LN siblings had unlimited to access to either chow and water, or chow, water and 25% sucrose solution. LN markedly reduced glucocorticoid receptor (GR) and neurogenic differentiation 1 (Neurod1) mRNA, markers involved in stress and hippocampal plasticity respectively, by more than 40%, with a similar effect of sugar intake in control rats. However, no further impact was observed in LN rats consuming sugar. Hippocampal Akt3 mRNA expression was similarly affected by LN and sucrose consumption. Interestingly, DNA methylation across 4 CpG sites of the GR and Neurod1 promoters was similar in LN and control rats. In summary, early life stress and post-weaning sugar intake produced long-term effects on hippocampal GR and Neurod1 expression. Moreover we found no evidence of altered promoter DNA methylation. We demonstrate for the first time that chronic sucrose consumption alone produces similar detrimental effects on the expression of hippocampal genes as LN exposure. PMID- 26834555 TI - Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats. AB - Stress is well-known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognized in the development of neurodegenerative disorders, such as Alzheimer's disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3, and 21 days) were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occluding, and glucose transporter-1) and astroglia (GFAP). Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, 1-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5, and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes, cognitive and behavioral dysfunctions. PMID- 26834556 TI - Myosin IXa Binds AMPAR and Regulates Synaptic Structure, LTP, and Cognitive Function. AB - Myosin IXa (Myo9a) is a motor protein that is highly expressed in the brain. However, the role of Myo9a in neurons remains unknown. Here, we investigated Myo9a function in hippocampal synapses. In rat hippocampal neurons, Myo9a localizes to the postsynaptic density (PSD) and binds the alpha-amino-3-hydroxy-5 methyl-4-isoxazole propionic acid receptor (AMPAR) GluA2 subunit. Myo9a(+/-) mice displayed a thicker PSD and increased levels of PSD95 and surface AMPAR expression. Furthermore, synaptic transmission, long-term potentiation (LTP) and cognitive functions were impaired in Myo9a(+/-) mice. Together, these results support a key role for Myo9a in controlling the molecular structure and function of hippocampal synapses. PMID- 26834558 TI - Axonal Kainate Receptors Modulate the Strength of Efferent Connectivity by Regulating Presynaptic Differentiation. AB - Kainate type of glutamate receptors (KARs) are highly expressed during early brain development and may influence refinement of the circuitry, via modulating synaptic transmission and plasticity. KARs are also localized to axons, however, their exact roles in regulating presynaptic processes remain controversial. Here, we have used a microfluidic chamber system allowing specific manipulation of KARs in presynaptic neurons to study their functions in synaptic development and function in vitro. Silencing expression of endogenous KARs resulted in lower density of synaptophysin immunopositive puncta in microfluidically isolated axons. Various recombinant KAR subunits and pharmacological compounds were used to dissect the mechanisms behind this effect. The calcium permeable (Q) variants of the low-affinity (GluK1-3) subunits robustly increased synaptophysin puncta in axons in a manner that was dependent on receptor activity and PKA and PKC dependent signaling. Further, an associated increase in the mean active zone length was observed in electron micrographs. Selective presynaptic expression of these subunits resulted in higher success rate of evoked EPSCs consistent with higher probability of glutamate release. In contrast, the calcium-impermeable (R) variant of GluK1 or the high-affinity subunits (GluK4,5) had no effect on synaptic density or transmission efficacy. These data suggest that calcium permeable axonal KARs promote efferent connectivity by increasing the density of functional presynaptic release sites. PMID- 26834557 TI - A Review of the Mechanisms of Blood-Brain Barrier Permeability by Tissue-Type Plasminogen Activator Treatment for Cerebral Ischemia. AB - Cerebrovascular homeostasis is maintained by the blood-brain barrier (BBB), which forms a mechanical and functional barrier between systemic circulation and the central nervous system (CNS). In patients with ischemic stroke, the recombinant tissue-type plasminogen activator (rt-PA) is used to accelerate recanalization of the occluded vessels. However, rt-PA is associated with a risk of increasing intracranial bleeding (ICB). This effect is thought to be caused by the increase in cerebrovascular permeability though various factors such as ischemic reperfusion injury and the activation of matrix metalloproteinases (MMPs), but the detailed mechanisms are unknown. It was recently found that rt-PA treatment enhances BBB permeability not by disrupting the BBB, but by activating the vascular endothelial growth factor (VEGF) system. The VEGF regulates both the dissociation of endothelial cell (EC) junctions and endothelial endocytosis, and causes a subsequent increase in vessel permeability through the VEGF receptor-2 (VEGFR-2) activation in ECs. Here, we review the possibility that rt-PA increases the penetration of toxic molecules derived from the bloodstream including rt-PA itself, without disrupting the BBB, and contributes to these detrimental processes in the cerebral parenchyma. PMID- 26834559 TI - Super-Resolution Microscopy Reveals Presynaptic Localization of the ALS/FTD Related Protein FUS in Hippocampal Neurons. AB - Fused in Sarcoma (FUS) is a multifunctional RNA-/DNA-binding protein, which is involved in the pathogenesis of the neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). A common hallmark of these disorders is the abnormal accumulation of mutated FUS protein in the cytoplasm. Under normal conditions FUS is confined to the nuclear compartment, in neurons, however, additional somatodendritic localization can be observed. In this study, we carefully analyzed the subcellular localization of endogenous FUS at synaptic sites of hippocampal neurons which are among the most affected cell types in FTD with FUS pathology. We could confirm a strong nuclear localization of FUS as well as its prominent and widespread neuronal expression throughout the adult and developing rat brain, particularly in the hippocampus, the cerebellum and the outer layers of the cortex. Intriguingly, FUS was also consistently observed at synaptic sites as detected by neuronal subcellular fractionation as well as by immunolabeling. To define a pre- and/or postsynaptic localization of FUS, we employed super-resolution fluorescence localization microscopy. FUS was found to be localized within the axon terminal in close proximity to the presynaptic vesicle protein Synaptophysin1 and adjacent to the active zone protein Bassoon, but well separated from the postsynaptic protein PSD-95. Having shown the presynaptic localization of FUS in the nervous system, a novel extranuclear role of FUS at neuronal contact sites has to be considered. Since there is growing evidence that local presynaptic translation might also be an important mechanism for plasticity, FUS - like the fragile X mental retardation protein FMRP - might act as one of the presynaptic RNA-binding proteins regulating this machinery. Our observation of presynaptic FUS should foster further investigations to determine its role in neurodegenerative diseases such as ALS and FTD. PMID- 26834561 TI - Editorial: Crosstalk between the Osteogenic and Neurogenic Stem Cell Niches: How Far are They from Each Other? PMID- 26834562 TI - Beyond Clotting: A Role of Platelets in CNS Repair? PMID- 26834564 TI - Layer Specific Development of Neocortical Pyramidal to Fast Spiking Cell Synapses. AB - All cortical neurons are engaged in inhibitory feedback loops which ensure excitation-inhibition balance and are key elements for the development of coherent network activity. The resulting network patterns are strongly dependent on the strength and dynamic properties of these excitatory-inhibitory loops which show pronounced regional and developmental diversity. Therefore we compared the properties and postnatal maturation of two different synapses between rat neocortical pyramidal cells (layer 2/3 and layer 5, respectively) and fast spiking (FS) interneurons in the corresponding layer. At P14, both synapses showed synaptic depression upon repetitive activation. Synaptic release properties between layer 2/3 pyramidal cells and FS cells were stable from P14 to P28. In contrast, layer 5 pyramidal to FS cell connections showed a significant increase in paired pulse ratio by P28. Presynaptic calcium dynamics also changed at these synapses, including sensitivity to exogenously loaded calcium buffers and expression of presynaptic calcium channel subtypes. These results underline the large variety of properties at different, yet similar, synapses in the neocortex. They also suggest that postnatal maturation of the brain goes along with increasing differences between synaptically driven network activity in layer 5 and layer 2/3. PMID- 26834563 TI - Space Takes Time: Concentration Dependent Output Codes from Primary Olfactory Networks Rapidly Provide Additional Information at Defined Discrimination Thresholds. AB - As odor concentration increases, primary olfactory network representations expand in spatial distribution, temporal complexity and duration. However, the direct relationship between concentration dependent odor representations and the psychophysical thresholds of detection and discrimination is poorly understood. This relationship is absolutely critical as thresholds signify transition points whereby representations become meaningful to the organism. Here, we matched stimulus protocols for psychophysical assays and intracellular recordings of antennal lobe (AL) projection neurons (PNs) in the moth Manduca sexta to directly compare psychophysical thresholds and the output representations they elicit. We first behaviorally identified odor detection and discrimination thresholds across an odor dilution series for a panel of structurally similar odors. We then characterized spatiotemporal spiking patterns across a population of individually filled and identified AL PNs in response to those odors at concentrations below, at, and above identified thresholds. Using spatial and spatiotemporal based analyses we observed that each stimulus produced unique representations, even at sub-threshold concentrations. Mean response latency did not decrease and the percent glomerular activation did not increase with concentration until undiluted odor. Furthermore, correlations between spatial patterns for odor decreased, but only significantly with undiluted odor. Using time-integrated Euclidean distance (ED) measures, we determined that added spatiotemporal information was present at the discrimination but not detection threshold. This added information was evidenced by an increase in integrated distance between the sub-detection and discrimination threshold concentrations (of the same odor) that was not present in comparison of the sub-detection and detection threshold. After consideration of delays for information to reach the AL we find that it takes ~120-140 ms for the AL to output identity information. Overall, these results demonstrate that as odor concentration increases, added information about odor identity is embedded in the spatiotemporal representation at the discrimination threshold. PMID- 26834565 TI - Relevance of Neuroinflammation and Encephalitis in Autism. AB - In recent years, many studies indicate that children with an autism spectrum disorder (ASD) diagnosis have brain pathology suggestive of ongoing neuroinflammation or encephalitis in different regions of their brains. Evidence of neuroinflammation or encephalitis in ASD includes: microglial and astrocytic activation, a unique and elevated proinflammatory profile of cytokines, and aberrant expression of nuclear factor kappa-light-chain-enhancer of activated B cells. A conservative estimate based on the research suggests that at least 69% of individuals with an ASD diagnosis have microglial activation or neuroinflammation. Encephalitis, which is defined as inflammation of the brain, is medical diagnosis code G04.90 in the International Classification of Disease, 10th revision; however, children with an ASD diagnosis are not generally assessed for a possible medical diagnosis of encephalitis. This is unfortunate because if a child with ASD has neuroinflammation, then treating the underlying brain inflammation could lead to improved outcomes. The purpose of this review of the literature is to examine the evidence of neuroinflammation/encephalitis in those with an ASD diagnosis and to address how a medical diagnosis of encephalitis, when appropriate, could benefit these children by driving more immediate and targeted treatments. PMID- 26834566 TI - Depression as a Glial-Based Synaptic Dysfunction. AB - Recent studies combining pharmacological, behavioral, electrophysiological and molecular approaches indicate that depression results from maladaptive neuroplastic processes occurring in defined frontolimbic circuits responsible for emotional processing such as the prefrontal cortex, hippocampus, amygdala and ventral striatum. However, the exact mechanisms controlling synaptic plasticity that are disrupted to trigger depressive conditions have not been elucidated. Since glial cells (astrocytes and microglia) tightly and dynamically interact with synapses, engaging a bi-directional communication critical for the processing of synaptic information, we now revisit the role of glial cells in the etiology of depression focusing on a dysfunction of the "quad-partite" synapse. This interest is supported by the observations that depressive-like conditions are associated with a decreased density and hypofunction of astrocytes and with an increased microglia "activation" in frontolimbic regions, which is expected to contribute for the synaptic dysfunction present in depression. Furthermore, the traditional culprits of depression (glucocorticoids, biogenic amines, brain derived neurotrophic factor, BDNF) affect glia functioning, whereas antidepressant treatments (serotonin-selective reuptake inhibitors, SSRIs, electroshocks, deep brain stimulation) recover glia functioning. In this context of a quad-partite synapse, systems modulating glia-synapse bidirectional communication-such as the purinergic neuromodulation system operated by adenosine 5'-triphosphate (ATP) and adenosine-emerge as promising candidates to "re normalize" synaptic function by combining direct synaptic effects with an ability to also control astrocyte and microglia function. This proposed triple action of purines to control aberrant synaptic function illustrates the rationale to consider the interference with glia dysfunction as a mechanism of action driving the design of future pharmacological tools to manage depression. PMID- 26834567 TI - Developmental Changes in Electrophysiological Properties and a Transition from Electrical to Chemical Coupling between Excitatory Layer 4 Neurons in the Rat Barrel Cortex. AB - During development, sensory systems switch from an immature to an adult mode of function along with the emergence of the active cortical states. Here, we used patch-clamp recordings from neocortical slices in vitro to characterize the developmental changes in the basic electrophysiological properties of excitatory L4 neurons and their connectivity before and after the developmental switch, which occurs in the rat barrel cortex in vivo at postnatal day P8. Prior to the switch, L4 neurons had higher resting membrane potentials, higher input resistance, lower membrane capacity, as well as action potentials (APs) with smaller amplitudes, longer durations and higher AP thresholds compared to the neurons after the switch. A sustained firing pattern also emerged around the switch. Dual patch-clamp recordings from L4 neurons revealed that recurrent connections between L4 excitatory cells do not exist before and develop rapidly across the switch. In contrast, electrical coupling between these neurons waned around the switch. We suggest that maturation of electrophysiological features, particularly acquisition of a sustained firing pattern, and a transition from the immature electrical to mature chemical synaptic coupling between excitatory L4 neurons, contributes to the developmental switch in the cortical mode of function. PMID- 26834560 TI - Exosomes as Novel Regulators of Adult Neurogenic Niches. AB - Adult neurogenesis has been convincingly demonstrated in two regions of the mammalian brain: the sub-granular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the sub-ventricular zone (SVZ) of the lateral ventricles (LV). SGZ newborn neurons are destined to the granular cell layer (GCL) of the DG, while new neurons from the SVZ neurons migrate rostrally into the olfactory bulb (OB). The process of adult neurogenesis persists throughout life and is supported by a pool of neural stem cells (NSCs), which reside in a unique and specialized microenvironment known as "neurogenic niche". Neurogenic niches are structured by a complex organization of different cell types, including the NSC-neuron lineage, glial cells and vascular cells. Thus, cell-to-cell communication plays a key role in the dynamic modulation of homeostasis and plasticity of the adult neurogenic process. Specific cell-cell contacts and extracellular signals originated locally provide the necessary support and regulate the balance between self-renewal and differentiation of NSCs. Furthermore, extracellular signals originated at distant locations, including other brain regions or systemic organs, may reach the niche through the cerebrospinal fluid (CSF) or the vasculature and influence its nature. The role of several secreted molecules, such as cytokines, growth factors, neurotransmitters, and hormones, in the biology of adult NSCs, has been systematically addressed. Interestingly, in addition to these well-recognized signals, a novel type of intercellular messengers has been identified recently: the extracellular vesicles (EVs). EVs, and particularly exosomes, are implicated in the transfer of mRNAs, microRNAs (miRNAs), proteins and lipids between cells and thus are able to modify the function of recipient cells. Exosomes appear to play a significant role in different stem cell niches such as the mesenchymal stem cell niche, cancer stem cell niche and pre-metastatic niche; however, their roles in adult neurogenic niches remain virtually unexplored. This review focuses on the current knowledge regarding the functional relationship between cellular and extracellular components of the adult SVZ and SGZ neurogenic niches, and the growing evidence that supports the potential role of exosomes in the physiology and pathology of adult neurogenesis. PMID- 26834568 TI - Neuromodulated Spike-Timing-Dependent Plasticity, and Theory of Three-Factor Learning Rules. AB - Classical Hebbian learning puts the emphasis on joint pre- and postsynaptic activity, but neglects the potential role of neuromodulators. Since neuromodulators convey information about novelty or reward, the influence of neuromodulators on synaptic plasticity is useful not just for action learning in classical conditioning, but also to decide "when" to create new memories in response to a flow of sensory stimuli. In this review, we focus on timing requirements for pre- and postsynaptic activity in conjunction with one or several phasic neuromodulatory signals. While the emphasis of the text is on conceptual models and mathematical theories, we also discuss some experimental evidence for neuromodulation of Spike-Timing-Dependent Plasticity. We highlight the importance of synaptic mechanisms in bridging the temporal gap between sensory stimulation and neuromodulatory signals, and develop a framework for a class of neo-Hebbian three-factor learning rules that depend on presynaptic activity, postsynaptic variables as well as the influence of neuromodulators. PMID- 26834570 TI - The Thalamus as a Low Pass Filter: Filtering at the Cellular Level does Not Equate with Filtering at the Network Level. AB - In the mammalian central nervous system, most sensory information passes through primary sensory thalamic nuclei, however the consequence of this remains unclear. Various propositions exist, likening the thalamus to a gate, or a high pass filter. Here, using a simple leaky integrate and fire model based on physiological parameters, we show that the thalamus behaves akin to a low pass filter. Specifically, as individual cells in the thalamus rely on consistent drive to spike, stimuli that is rapidly and continuously changing over time such that it activates sensory cells with different receptive fields are unable to drive thalamic spiking. This means that thalamic encoding is robust to sensory noise, however it induces a lag in sensory representation. Thus, the thalamus stabilizes encoding of sensory information, at the cost of response rate. PMID- 26834571 TI - Extrinsic Sources of Cholinergic Innervation of the Striatal Complex: A Whole Brain Mapping Analysis. AB - Acetylcholine in the striatal complex plays an important role in normal behavior and is affected in a number of neurological disorders. Although early studies suggested that acetylcholine in the striatum (STR) is derived almost exclusively from cholinergic interneurons (CIN), recent axonal mapping studies using conditional anterograde tracing have revealed the existence of a prominent direct cholinergic pathway from the pedunculopontine and laterodorsal tegmental nuclei to the dorsal striatum and nucleus accumbens. The identification of the importance of this pathway is essential for creating a complete model of cholinergic modulation in the striatum, and it opens the question as to whether other populations of cholinergic neurons may also contribute to such modulation. Here, using novel viral tracing technologies based on phenotype-specific fluorescent reporter expression in combination with retrograde tracing, we aimed to define other sources of cholinergic innervation of the striatum. Systematic mapping of the projections of all cholinergic structures in the brain (Ch1 to Ch8) by means of conditional tracing of cholinergic axons, revealed that the only extrinsic source of cholinergic innervation arises in the brainstem pedunculopontine and laterodorsal tegmental nuclei. Our results thus place the pedunculopontine and laterodorsal nuclei in a key and exclusive position to provide extrinsic cholinergic modulation of the activity of the striatal systems. PMID- 26834573 TI - Closed-Loop Brain Model of Neocortical Information-Based Exchange. AB - Here we describe an "information-based exchange" model of brain function that ascribes to neocortex, basal ganglia, and thalamus distinct network functions. The model allows us to analyze whole brain system set point measures, such as the rate and heterogeneity of transitions in striatum and neocortex, in the context of neuromodulation and other perturbations. Our closed-loop model is grounded in neuroanatomical observations, proposing a novel "Grand Loop" through neocortex, and invokes different forms of plasticity at specific tissue interfaces and their principle cell synapses to achieve these transitions. By implementing a system for maximum information-based exchange of action potentials between modeled neocortical areas, we observe changes to these measures in simulation. We hypothesize that similar dynamic set points and modulations exist in the brain's resting state activity, and that different modifications to information-based exchange may shift the risk profile of different component tissues, resulting in different neurodegenerative diseases. This model is targeted for further development using IBM's Neural Tissue Simulator, which allows scalable elaboration of networks, tissues, and their neural and synaptic components toward ever greater complexity and biological realism. PMID- 26834572 TI - Asymmetry of Radial and Symmetry of Tangential Neuronal Migration Pathways in Developing Human Fetal Brains. AB - The radial and tangential neural migration pathways are two major neuronal migration streams in humans that are critical during corticogenesis. Corticogenesis is a complex process of neuronal proliferation that is followed by neuronal migration and the formation of axonal connections. Existing histological assessments of these two neuronal migration pathways have limitations inherent to microscopic studies and are confined to small anatomic regions of interest (ROIs). Thus, little evidence is available about their three-dimensional (3-D) fiber pathways and development throughout the entire brain. In this study, we imaged and analyzed radial and tangential migration pathways in the whole human brain using high-angular resolution diffusion MR imaging (HARDI) tractography. We imaged ten fixed, postmortem fetal (17 gestational weeks (GW), 18 GW, 19 GW, three 20 GW, three 21 GW and 22 GW) and eight in vivo newborn (two 30 GW, 34 GW, 35 GW and four 40 GW) brains with no neurological/pathological conditions. We statistically compared the volume of the left and right radial and tangential migration pathways, and the volume of the radial migration pathways of the anterior and posterior regions of the brain. In specimens 22 GW or younger, the volume of radial migration pathways of the left hemisphere was significantly larger than that of the right hemisphere. The volume of posterior radial migration pathways was also larger when compared to the anterior pathways in specimens 22 GW or younger. In contrast, no significant differences were observed in the radial migration pathways of brains older than 22 GW. Moreover, our study did not identify any significant differences in volumetric laterality in the tangential migration pathways. These results suggest that these two neuronal migration pathways develop and regress differently, and radial neuronal migration varies regionally based on hemispheric and anterior-posterior laterality, potentially explaining regional differences in the amount of excitatory neurons that migrate along the radial scaffold. PMID- 26834574 TI - Brodmann's Area Template Based Region of Interest Setting and Probabilistic Pathway Map Generation in Diffusion Tensor Tractography: Application to the Arcuate Fasciculus Fiber Tract in the Human Brain. AB - The purpose of this study is to acquire accurate diffusion tensor tractography (DTT) results for arcuate fasciculus (AF) fiber tract using Brodmann's area (BA) template for region of interest (ROI) setting. Thirteen healthy subjects were participated in this study. Fractional anisotropy (FA) map of each subject was calculated using diffusion tensor data, and T1w template was co-registered to FA map. The BA template was also co-registered using the transformation matrix. The ROIs were drawn in the co-registered BA template, and AF fiber tract was extracted. To generate the probabilistic pathway map, a binary mask image was generated based on the fiber tract image and co-registered to T1w template image. We also measured relative location of the AF fiber tract. The location of the probabilistic pathway map of each subject's AF fiber tract was well defined in the brain. By using this probabilistic map, the mediolateral position ratio of AF was measured 18%, and the anteroposterior position ratio of AF was measured 35%, respectively. This study demonstrated that the AF fiber tract can be extracted using BA template for ROI setting and probabilistic pathway of fiber tract. Our results and analytical approaches can helpful for accurate fiber tracking and application of perspective clinical researches. PMID- 26834569 TI - The Slow Oscillation in Cortical and Thalamic Networks: Mechanisms and Functions. AB - During even the most quiescent behavioral periods, the cortex and thalamus express rich spontaneous activity in the form of slow (<1 Hz), synchronous network state transitions. Throughout this so-called slow oscillation, cortical and thalamic neurons fluctuate between periods of intense synaptic activity (Up states) and almost complete silence (Down states). The two decades since the original characterization of the slow oscillation in the cortex and thalamus have seen considerable advances in deciphering the cellular and network mechanisms associated with this pervasive phenomenon. There are, nevertheless, many questions regarding the slow oscillation that await more thorough illumination, particularly the mechanisms by which Up states initiate and terminate, the functional role of the rhythmic activity cycles in unconscious or minimally conscious states, and the precise relation between Up states and the activated states associated with waking behavior. Given the substantial advances in multineuronal recording and imaging methods in both in vivo and in vitro preparations, the time is ripe to take stock of our current understanding of the slow oscillation and pave the way for future investigations of its mechanisms and functions. My aim in this Review is to provide a comprehensive account of the mechanisms and functions of the slow oscillation, and to suggest avenues for further exploration. PMID- 26834575 TI - High Resolution MRI Reveals Detailed Layer Structures in Early Human Fetal Stages: In Vitro Study with Histologic Correlation. AB - An understanding of normal fetal brain development is essential in detecting the early onset of brain disorders. It is challenging to obtain high-quality images that show detailed local anatomy in the early fetal stages because the fetal brain is very small with rapidly-changing complex structures related to brain development, including neurogenesis, neuronal migration, and axonal elongation. Previous magnetic resonance imaging (MRI) studies detected three layers throughout the fetal cerebral wall that showed differences in MR contrasts at 10 gestational weeks (GW), which is one of the earliest ages studied using MRI. Contrary to the MRI studies, histological studies found more layers at this fetal age. The purpose of this work is to study the development of brain structures from an early fetal period to an early second trimester stage using ex vivo MRI and compare it to histology. Special attention was paid to laminar structures in the cerebral wall. T2-weighted imaging was performed on fetal brain specimens ranging from 10 GW to 18 GW on a 4.7 tesla MR scanner. We obtained standard grayscale as well as color-coded images using weighted red-green-blue scales, and compared them with the histological images. Our study confirmed laminar structure in the cerebral wall in all the fetal specimens studied. We found that MRI detected four layers within the cerebral wall as early as 10 GW during the early fetal period (10-13 GW). Early second trimester (15-18 GW) was characterized by the emergence of subplate structures and five layers within the cerebral wall. The color-coded images were more useful than the standard grayscale images in detecting the laminar structures. Scans with appropriate parameters from a high tesla MR scanner showed detailed laminar structures even through a very small and thin cerebral wall at 10 GW ex vivo. A combination of high-resolution structural imaging and color-coding processing with histological analysis may be a potential tool for studying detailed structures of typical developing fetal brains, as well as fetal brains with developmental disorders as references for clinical MRI. PMID- 26834576 TI - Multivariate Analyses Applied to Healthy Neurodevelopment in Fetal, Neonatal, and Pediatric MRI. AB - Multivariate analysis (MVA) is a class of statistical and pattern recognition techniques that involve the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of neurological medical imaging related challenges including the evaluation of healthy brain development, the automated analysis of brain tissues and structures through image segmentation, evaluating the effects of genetic and environmental factors on brain development, evaluating sensory stimulation's relationship with functional brain activity and much more. Compared to adult imaging, pediatric, neonatal and fetal imaging have attracted less attention from MVA researchers, however, recent years have seen remarkable MVA research growth in pre-adult populations. This paper presents the results of a systematic review of the literature focusing on MVA applied to healthy subjects in fetal, neonatal and pediatric magnetic resonance imaging (MRI) of the brain. While the results of this review demonstrate considerable interest from the scientific community in applications of MVA technologies in brain MRI, the field is still young and significant research growth will continue into the future. PMID- 26834577 TI - Reorganization of Basolateral Amygdala-Subiculum Circuitry in Mouse Epilepsy Model. AB - In this study, we investigated the reorganized basolateral amygdala (BLA) subiculum pathway in a status epilepticus (SE) mouse model with epileptic episodes induced by pilocarpine. We have previously observed a dramatic loss of neurons in the CA1-3 fields of the hippocampus in epileptic mice. Herein, we observed a 43-57% reduction in the number of neurons in the BLA of epileptic mice. However, injection of an anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L) into the BLA indicated 25.63% increase in the number of PHA-L-immunopositive terminal-like structures in the ventral subiculum (v-Sub) of epileptic mice as compared to control mice. These data suggest that the projections from the basal nucleus at BLA to the vSub in epileptic mice are resistant to epilepsy-induced damage. Consequently, these epileptic mice exhibit partially impairment but not total loss of context-dependent fear memory. Epileptic mice also show increased c-Fos expression in the BLA and vSub when subjected to contextual memory test, suggesting the participation of these two brain areas in foot shock-dependent fear conditioning. These results indicate the presence of functional neural connections between the BLA-vSub regions that participate in learning and memory in epileptic mice. PMID- 26834578 TI - Dopaminergic Input to the Inferior Colliculus in Mice. AB - The response of sensory neurons to stimuli can be modulated by a variety of factors including attention, emotion, behavioral context, and disorders involving neuromodulatory systems. For example, patients with Parkinson's disease (PD) have disordered speech processing, suggesting that dopamine alters normal representation of these salient sounds. Understanding the mechanisms by which dopamine modulates auditory processing is thus an important goal. The principal auditory midbrain nucleus, the inferior colliculus (IC), is a likely location for dopaminergic modulation of auditory processing because it contains dopamine receptors and nerve terminals immunoreactive for tyrosine hydroxylase (TH), the rate-limiting enzyme in dopamine synthesis. However, the sources of dopaminergic input to the IC are unknown. In this study, we iontophoretically injected a retrograde tracer into the IC of mice and then stained the tissue for TH. We also immunostained for dopamine beta-hydroxylase (DBH), an enzyme critical for the conversion of dopamine to norepinephrine, to differentiate between dopaminergic and noradrenergic inputs. Retrogradely labeled neurons that were positive for TH were seen bilaterally, with strong ipsilateral dominance, in the subparafascicular thalamic nucleus (SPF). All retrogradely labeled neurons that we observed in other brain regions were TH-negative. Projections from the SPF were confirmed using an anterograde tracer, revealing TH-positive and DBH negative anterogradely labeled fibers and terminals in the IC. While the functional role of this dopaminergic input to the IC is not yet known, it provides a potential mechanism for context dependent modulation of auditory processing. PMID- 26834580 TI - Statistical Frequency-Dependent Analysis of Trial-to-Trial Variability in Single Time Series by Recurrence Plots. AB - For decades, research in neuroscience has supported the hypothesis that brain dynamics exhibits recurrent metastable states connected by transients, which together encode fundamental neural information processing. To understand the system's dynamics it is important to detect such recurrence domains, but it is challenging to extract them from experimental neuroscience datasets due to the large trial-to-trial variability. The proposed methodology extracts recurrent metastable states in univariate time series by transforming datasets into their time-frequency representations and computing recurrence plots based on instantaneous spectral power values in various frequency bands. Additionally, a new statistical inference analysis compares different trial recurrence plots with corresponding surrogates to obtain statistically significant recurrent structures. This combination of methods is validated by applying it to two artificial datasets. In a final study of visually-evoked Local Field Potentials in partially anesthetized ferrets, the methodology is able to reveal recurrence structures of neural responses with trial-to-trial variability. Focusing on different frequency bands, the delta-band activity is much less recurrent than alpha-band activity. Moreover, alpha-activity is susceptible to pre-stimuli, while delta-activity is much less sensitive to pre-stimuli. This difference in recurrence structures in different frequency bands indicates diverse underlying information processing steps in the brain. PMID- 26834579 TI - Neural Substrate Expansion for the Restoration of Brain Function. AB - Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not demonstrated the ability to reestablish the function of large-scale neuronal networks. In this review, we contend that fulfilling the potential of brain substrate expansion will require a significant shift from current methods that emphasize direct manipulations of the brain (e.g., injections of cellular suspensions and the implantation of multi-electrode arrays) to the generation of more sophisticated neural tissues and neural-electric hybrids in vitro that are subsequently transplanted into the brain. Drawing from neural tissue engineering, stem cell biology, and neural interface technologies, this strategy makes greater use of the manifold techniques available in the laboratory to create biocompatible constructs that recapitulate brain architecture and thus are more easily recognized and utilized by brain networks. PMID- 26834583 TI - Assessing Granger Causality in Electrophysiological Data: Removing the Adverse Effects of Common Signals via Bipolar Derivations. AB - Multielectrode voltage data are usually recorded against a common reference. Such data are frequently used without further treatment to assess patterns of functional connectivity between neuronal populations and between brain areas. It is important to note from the outset that such an approach is valid only when the reference electrode is nearly electrically silent. In practice, however, the reference electrode is generally not electrically silent, thereby adding a common signal to the recorded data. Volume conduction further complicates the problem. In this study we demonstrate the adverse effects of common signals on the estimation of Granger causality, which is a statistical measure used to infer synaptic transmission and information flow in neural circuits from multielectrode data. We further test the hypothesis that the problem can be overcome by utilizing bipolar derivations where the difference between two nearby electrodes is taken and treated as a representation of local neural activity. Simulated data generated by a neuronal network model where the connectivity pattern is known were considered first. This was followed by analyzing data from three experimental preparations where a priori predictions regarding the patterns of causal interactions can be made: (1) laminar recordings from the hippocampus of an anesthetized rat during theta rhythm, (2) laminar recordings from V4 of an awake-behaving macaque monkey during alpha rhythm, and (3) ECoG recordings from electrode arrays implanted in the middle temporal lobe and prefrontal cortex of an epilepsy patient during fixation. For both simulation and experimental analysis the results show that bipolar derivations yield the expected connectivity patterns whereas the untreated data (referred to as unipolar signals) do not. In addition, current source density signals, where applicable, yield results that are close to the expected connectivity patterns, whereas the commonly practiced average re-reference method leads to erroneous results. PMID- 26834581 TI - The Monitoring and Control of Task Sequences in Human and Non-Human Primates. AB - Our ability to plan and execute a series of tasks leading to a desired goal requires remarkable coordination between sensory, motor, and decision-related systems. Prefrontal cortex (PFC) is thought to play a central role in this coordination, especially when actions must be assembled extemporaneously and cannot be programmed as a rote series of movements. A central component of this flexible behavior is the moment-by-moment allocation of working memory and attention. The ubiquity of sequence planning in our everyday lives belies the neural complexity that supports this capacity, and little is known about how frontal cortical regions orchestrate the monitoring and control of sequential behaviors. For example, it remains unclear if and how sensory cortical areas, which provide essential driving inputs for behavior, are modulated by the frontal cortex during these tasks. Here, we review what is known about moment-to-moment monitoring as it relates to visually guided, rule-driven behaviors that change over time. We highlight recent human work that shows how the rostrolateral prefrontal cortex (RLPFC) participates in monitoring during task sequences. Neurophysiological data from monkeys suggests that monitoring may be accomplished by neurons that respond to items within the sequence and may in turn influence the tuning properties of neurons in posterior sensory areas. Understanding the interplay between proceduralized or habitual acts and supervised control of sequences is key to our understanding of sequential task execution. A crucial bridge will be the use of experimental protocols that allow for the examination of the functional homology between monkeys and humans. We illustrate how task sequences may be parceled into components and examined experimentally, thereby opening future avenues of investigation into the neural basis of sequential monitoring and control. PMID- 26834584 TI - Impact of Auditory Context on Executed Motor Actions. AB - The auditory and motor systems are strongly coupled, as is evident in the specifically tight motor synchronization that occurs in response to regularly occurring auditory cues compared with cues of other modalities. Timing of rhythmic action is known to rely on multiple neural centers including the cerebellum and the basal-ganglia which have access to both motor cortical and spinal circuitries. To date, however, there is little information on the motor mechanisms that operate during preparation and execution of rhythmic vs. non rhythmic movements. We measured acceleration profile and muscle activity while subjects performed tapping movements in response to auditory cues. We found that when tapping at random intervals there was a higher variability of both acceleration profile and muscle activity during motor preparation compared to rhythmic tapping. However, the specific rhythmic context (cued, self-paced, or syncopation) did not affect the motor parameters of the executed taps. Finally, during entrainment we found a gradual as opposed to episodic change in low-level motor parameters (i.e., preparatory muscle activity) that was strongly correlated with changes in high-level parameters (i.e., shift in the reaction time to negative asynchrony). These findings suggest that motor entrainment involves not only adjusting the timing of movement but also modifying parameters that are related to its production. These changes in motor output were insensitive to the specifics of the rhythmic cue: although it took subjects different times to become entrained to different types of rhythmic cues, the motor actions produced once entrainment was obtained were indistinguishable. These findings suggest that motor entrainment involves not only adjusting the timing of movement but also modifying parameters related to its production. The reduced variability of muscle activity during the preparatory period could be one mechanism used by the motor system to enhance the accuracy of motor timing. PMID- 26834582 TI - Cell-Type and State-Dependent Synchronization among Rodent Somatosensory, Visual, Perirhinal Cortex, and Hippocampus CA1. AB - Beta and gamma rhythms have been hypothesized to be involved in global and local coordination of neuronal activity, respectively. Here, we investigated how cells in rodent area S1BF are entrained by rhythmic fluctuations at various frequencies within the local area and in connected areas, and how this depends on behavioral state and cell type. We performed simultaneous extracellular field and unit recordings in four connected areas of the freely moving rat (S1BF, V1M, perirhinal cortex, CA1). S1BF spiking activity was strongly entrained by both beta and gamma S1BF oscillations, which were associated with deactivations and activations, respectively. We identified multiple classes of fast spiking and excitatory cells in S1BF, which showed prominent differences in rhythmic entrainment and in the extent to which phase locking was modulated by behavioral state. Using an additional dataset acquired by whole-cell recordings in head fixed mice, these cell classes could be compared with identified phenotypes showing gamma rhythmicity in their membrane potential. We next examined how S1BF cells were entrained by rhythmic fluctuations in connected brain areas. Gamma synchronization was detected in all four areas, however we did not detect significant gamma coherence among these areas. Instead, we only found long-range coherence in the theta-beta range among these areas. In contrast to local S1BF synchronization, we found long-range S1BF-spike to CA1-LFP synchronization to be homogeneous across inhibitory and excitatory cell types. These findings suggest distinct, cell-type contributions of low and high-frequency synchronization to intra- and inter-areal neuronal interactions. PMID- 26834585 TI - Positive Emotion Facilitates Audiovisual Binding. AB - It has been shown that positive emotions can facilitate integrative and associative information processing in cognitive functions. The present study examined whether emotions in observers can also enhance perceptual integrative processes. We tested 125 participants in total for revealing the effects of emotional states and traits in observers on the multisensory binding between auditory and visual signals. Participants in Experiment 1 observed two identical visual disks moving toward each other, coinciding, and moving away, presented with a brief sound. We found that for participants with lower depressive tendency, induced happy moods increased the width of the temporal binding window of the sound-induced bounce percept in the stream/bounce display, while no effect was found for the participants with higher depressive tendency. In contrast, no effect of mood was observed for a simple audiovisual simultaneity discrimination task in Experiment 2. These results provide the first empirical evidence of a dependency of multisensory binding upon emotional states and traits, revealing that positive emotions can facilitate the multisensory binding processes at a perceptual level. PMID- 26834587 TI - Characteristics of Eye-Position Gain Field Populations Determine Geometry of Visual Space. AB - We have previously demonstrated differences in eye-position spatial maps for anterior inferotemporal cortex (AIT) in the ventral stream and lateral intraparietal cortex (LIP) in the dorsal stream, based on population decoding of gaze angle modulations of neural visual responses (i.e., eye-position gain fields). Here we explore the basis of such spatial encoding differences through modeling of gain field characteristics. We created a population of model neurons, each having a different eye-position gain field. This population was used to reconstruct eye-position visual space using multidimensional scaling. As gain field shapes have never been well-established experimentally, we examined different functions, including planar, sigmoidal, elliptical, hyperbolic, and mixtures of those functions. All functions successfully recovered positions, indicating weak constraints on allowable gain field shapes. We then used a genetic algorithm to modify the characteristics of model gain field populations until the recovered spatial maps closely matched those derived from monkey neurophysiological data in AIT and LIP. The primary differences found between model AIT and LIP gain fields were that AIT gain fields were more foveally dominated. That is, gain fields in AIT operated on smaller spatial scales and smaller dispersions than in LIP. Thus, we show that the geometry of eye-position visual space depends on the population characteristics of gain fields, and that differences in gain field characteristics for different cortical areas may underlie differences in the representation of space. PMID- 26834586 TI - Role of Glycogenolysis in Memory and Learning: Regulation by Noradrenaline, Serotonin and ATP. AB - This paper reviews the role played by glycogen breakdown (glycogenolysis) and glycogen re-synthesis in memory processing in two different chick brain regions, (1) the hippocampus and (2) the avian equivalent of the mammalian cortex, the intermediate medial mesopallium (IMM). Memory processing is regulated by the neuromodulators noradrenaline and serotonin soon after training glycogen breakdown and re-synthesis. In day-old domestic chicks, memory formation is dependent on the breakdown of glycogen (glycogenolysis) at three specific times during the first 60 min after learning (around 2.5, 30, and 55 min). The chicks learn to discriminate in a single trial between beads of two colors and tastes. Inhibition of glycogen breakdown by the inhibitor of glycogen phosphorylase 1,4 dideoxy-1,4-imino-D-arabinitol (DAB) given at specific times prior to the formation of long-term memory prevents memory forming. Noradrenergic stimulation of cultured chicken astrocytes by a selective beta2-adrenergic (AR) agonist reduces glycogen levels and we believe that in vivo this triggers memory consolidation at the second stage of glycogenolysis. Serotonin acting at 5-HT2B receptors acts on the first stage, but not on the second. We have shown that noradrenaline, acting via post-synaptic alpha2-ARs, is also responsible for the synthesis of glycogen and our experiments suggest that there is a readily accessible labile pool of glycogen in astrocytes which is depleted within 10 min if glycogen synthesis is inhibited. Endogenous ATP promotion of memory consolidation at 2.5 and 30 min is also dependent on glycogen breakdown. ATP acts at P2Y1 receptors and the action of thrombin suggests that it causes the release of internal calcium ([Ca(2+)]i) in astrocytes. Glutamate and GABA, the primary neurotransmitters in the brain, cannot be synthesized in neurons de novo and neurons rely on astrocytic glutamate synthesis, requiring glycogenolysis. PMID- 26834588 TI - Deciphering Resting Microglial Morphology and Process Motility from a Synaptic Prospect. AB - Microglia, the resident immune cells of the central nervous system (CNS), were traditionally believed to be set into action only in case of injury or disease. Accordingly, microglia were assumed to be inactive or resting in the healthy brain. However, recent studies revealed that microglia carry out active tissue sampling in the intact brain by extending and retracting their ramified processes while periodically contacting synapses. Microglial morphology and motility as well as the frequency and duration of physical contacts with synaptic elements were found to be modulated by neuronal activity, sensory experience and neurotransmission; however findings have not been straightforward. Microglial cells are the most morphologically plastic element of the CNS. This unique feature confers them the possibility to locally sense activity, and to respond adequately by establishing synaptic contacts to regulate synaptic inputs by the secretion of signaling molecules. Indeed, microglial cells can hold new roles as critical players in maintaining brain homeostasis and regulating synaptic number, maturation and plasticity. For this reason, a better characterization of microglial cells and cues mediating neuron-to-microglia communication under physiological conditions may help advance our understanding of the microglial behavior and its regulation in the healthy brain. This review highlights recent findings on the instructive role of neuronal activity on microglial motility and microglia-synapse interactions, focusing on the main transmitters involved in this communication and including newly described communication at the tripartite synapse. PMID- 26834589 TI - Parallel Olfactory Processing in the Honey Bee Brain: Odor Learning and Generalization under Selective Lesion of a Projection Neuron Tract. AB - The function of parallel neural processing is a fundamental problem in Neuroscience, as it is found across sensory modalities and evolutionary lineages, from insects to humans. Recently, parallel processing has attracted increased attention in the olfactory domain, with the demonstration in both insects and mammals that different populations of second-order neurons encode and/or process odorant information differently. Among insects, Hymenoptera present a striking olfactory system with a clear neural dichotomy from the periphery to higher-order centers, based on two main tracts of second-order (projection) neurons: the medial and lateral antennal lobe tracts (m-ALT and l-ALT). To unravel the functional role of these two pathways, we combined specific lesions of the m-ALT tract with behavioral experiments, using the classical conditioning of the proboscis extension response (PER conditioning). Lesioned and intact bees had to learn to associate an odorant (1-nonanol) with sucrose. Then the bees were subjected to a generalization procedure with a range of odorants differing in terms of their carbon chain length or functional group. We show that m-ALT lesion strongly affects acquisition of an odor-sucrose association. However, lesioned bees that still learned the association showed a normal gradient of decreasing generalization responses to increasingly dissimilar odorants. Generalization responses could be predicted to some extent by in vivo calcium imaging recordings of l-ALT neurons. The m-ALT pathway therefore seems necessary for normal classical olfactory conditioning performance. PMID- 26834591 TI - The Role of Psychological and Physiological Factors in Decision Making under Risk and in a Dilemma. AB - Different methods to elicit risk attitudes of individuals often provide differing results despite a common theory. Reasons for such inconsistencies may be the different influence of underlying factors in risk-taking decisions. In order to evaluate this conjecture, a better understanding of underlying factors across methods and decision contexts is desirable. In this paper we study the difference in result of two different risk elicitation methods by linking estimates of risk attitudes to gender, age, and personality traits, which have been shown to be related. We also investigate the role of these factors during decision-making in a dilemma situation. For these two decision contexts we also investigate the decision-maker's physiological state during the decision, measured by heart rate variability (HRV), which we use as an indicator of emotional involvement. We found that the two elicitation methods provide different individual risk attitude measures which is partly reflected in a different gender effect between the methods. Personality traits explain only relatively little in terms of driving risk attitudes and the difference between methods. We also found that risk taking and the physiological state are related for one of the methods, suggesting that more emotionally involved individuals are more risk averse in the experiment. Finally, we found evidence that personality traits are connected to whether individuals made a decision in the dilemma situation, but risk attitudes and the physiological state were not indicative for the ability to decide in this decision context. PMID- 26834590 TI - Cross-Species Integrative Functional Genomics in GeneWeaver Reveals a Role for Pafah1b1 in Altered Response to Alcohol. AB - Identifying the biological substrates of complex neurobehavioral traits such as alcohol dependency pose a tremendous challenge given the diverse model systems and phenotypic assessments used. To address this problem we have developed a platform for integrated analysis of high-throughput or genome-wide functional genomics studies. A wealth of such data exists, but it is often found in disparate, non-computable forms. Our interactive web-based software system, Gene Weaver (http://www.geneweaver.org), couples curated results from genomic studies to graph-theoretical tools for combinatorial analysis. Using this system we identified a gene underlying multiple alcohol-related phenotypes in four species. A search of over 60,000 gene sets in GeneWeaver's database revealed alcohol related experimental results including genes identified in mouse genetic mapping studies, alcohol selected Drosophila lines, Rattus differential expression, and human alcoholic brains. We identified highly connected genes and compared these to genes currently annotated to alcohol-related behaviors and processes. The most highly connected gene not annotated to alcohol was Pafah1b1. Experimental validation using a Pafah1b1 conditional knock-out mouse confirmed that this gene is associated with an increased preference for alcohol and an altered thermoregulatory response to alcohol. Although this gene has not been previously implicated in alcohol-related behaviors, its function in various neural mechanisms makes a role in alcohol-related phenomena plausible. By making diverse cross-species functional genomics data readily computable, we were able to identify and confirm a novel alcohol-related gene that may have implications for alcohol use disorders and other effects of alcohol. PMID- 26834592 TI - Investigating Factors that Generate and Maintain Variation in Migratory Orientation: A Primer for Recent and Future Work. AB - The amazing accuracy of migratory orientation performance across the animal kingdom is facilitated by the use of magnetic and celestial compass systems that provide individuals with both directional and positional information. Quantitative genetics analyses in several animal systems suggests that migratory orientation has a strong genetic component. Nevertheless, the exact identity of genes controlling orientation remains largely unknown, making it difficult to obtain an accurate understanding of this fascinating behavior on the molecular level. Here, we provide an overview of molecular genetic techniques employed thus far, highlight the pros and cons of various approaches, generalize results from species-specific studies whenever possible, and evaluate how far the field has come since early quantitative genetics studies. We emphasize the importance of examining different levels of molecular control, and outline how future studies can take advantage of high-resolution tracking and sequencing techniques to characterize the genomic architecture of migratory orientation. PMID- 26834593 TI - Beta Band Transcranial Alternating (tACS) and Direct Current Stimulation (tDCS) Applied After Initial Learning Facilitate Retrieval of a Motor Sequence. AB - The primary motor cortex (M1) contributes to the acquisition and early consolidation of a motor sequence. Although the relevance of M1 excitability for motor learning has been supported, the significance of M1 oscillations remains an open issue. This study aims at investigating to what extent retrieval of a newly learned motor sequence can be differentially affected by motor-cortical transcranial alternating (tACS) and direct current stimulation (tDCS). Alpha (10 Hz), beta (20 Hz) or sham tACS was applied in 36 right-handers. Anodal or cathodal tDCS was applied in 30 right-handers. Participants learned an eight digit serial reaction time task (SRTT; sequential vs. random) with the right hand. Stimulation was applied to the left M1 after SRTT acquisition at rest for 10 min. Reaction times were analyzed at baseline, end of acquisition, retrieval immediately after stimulation and reacquisition after eight further sequence repetitions. Reaction times during retrieval were significantly faster following 20 Hz tACS as compared to 10 Hz and sham tACS indicating a facilitation of early consolidation. tDCS yielded faster reaction times, too, independent of polarity. No significant differences between 20 Hz tACS and tDCS effects on retrieval were found suggesting that 20 Hz effects might be associated with altered motor cortical excitability. Based on the behavioral modulation yielded by tACS and tDCS one might speculate that altered motor-cortical beta oscillations support early motor consolidation possibly associated with neuroplastic reorganization. PMID- 26834594 TI - Decreased Intra- and Inter-Salience Network Functional Connectivity is Related to Trait Anxiety in Adolescents. AB - OBJECTIVE: Adolescence is a critical period for the vulnerability of anxiety. Imaging studies focusing on adolescents' susceptibility to anxiety suggest that the different development trajectories between the limbic system and the executive control system may play important roles in this phenomenon. However, few studies have explored the brain basis of this susceptibility from the perspective of functional networks. The salience network (SN) consists of a series of key limbic and prefrontal regions that are engaged in the development of anxiety, such as the amygdala, anterior insula (AI), and dorsal anterior cingulate cortex (dACC). Intra- and inter-network connections in this system play essential roles in bottom-up attention and top-down regulation of anxiety, nevertheless, little is known about whether the SN-centered connections are associated with trait anxiety (i.e., susceptibility to anxiety) in adolescents. METHOD: Here, we applied resting-state functional magnetic resonance imaging (fMRI) to explore the relationship between intra- and inter-network functional connectivity (FC) of the SN and trait anxiety in adolescents using the amygdala, AI and dACC as the regions of interest (ROI). RESULTS: We found that trait anxiety levels were inversely associated with both characteristic AI-dACC FC in the SN and distributed inter-network FC between the SN and multiple functional systems, which included the default mode network and the executive control network. CONCLUSIONS: Our results indicate that weaker intra- and inter-network FC of the SN was linked to higher trait anxiety among adolescents, and it may underlie altered salience processing and cognitive regulation. PMID- 26834595 TI - Role of Aging and Hippocampus in Time-Place Learning: Link to Episodic-Like Memory? AB - INTRODUCTION: With time-place learning (TPL), animals link an event with the spatial location and the time of day (TOD). The what-where-when TPL components make the task putatively episodic-like in nature. Animals use an internal sense of time to master TPL, which is circadian system based. Finding indications for a role of the hippocampus and (early) aging-sensitivity in TPL would strengthen the episodic-like memory nature of the paradigm. METHODS: Previously, we used C57Bl/6 mice for our TPL research. Here, we used CD1 mice which are less hippocampal driven and age faster compared to C57Bl/6 mice. To demonstrate the low degree of hippocampal-driven performance in CD1 mice, a cross maze was used. The spontaneous alternation test was used to score spatial working memory in CD1 mice at four different age categories (young (3-6 months), middle-aged (7-11 months), aged (12-18 months) and old (>19 months). TPL performance of middle-aged and aged CD1 mice was tested in a setup with either two or three time points per day (2 arm or 3-arm TPL task). Immunostainings were applied on brains of young and middle-aged C57Bl/6 mice that had successfully mastered the 3-arm TPL task. RESULTS: In contrast to C57Bl/6 mice, middle-aged and aged CD1 mice were less hippocampus-driven and failed to master the 3-arm TPL task. They could, however, master the 2-arm TPL task primarily via an ordinal (non-circadian) timing system. c-Fos, CRY2, vasopressin (AVP), and phosphorylated cAMP response element-binding protein (pCREB) were investigated. We found no differences at the level of the suprachiasmatic nucleus (SCN; circadian master clock), whereas CRY2 expression was increased in the hippocampal dentate gyrus (DG). The most pronounced difference between TPL trained and control mice was found in c-Fos expression in the paraventricular thalamic nucleus, a circadian system relay station. CONCLUSIONS: These results further indicate a key role of CRY proteins in TPL and confirm the limited role of the SCN in TPL. Based on the poor TPL performance of CD1 mice, the results suggest age-sensitivity and hippocampal involvement in TPL. We suspect that TPL reflects an episodic-like memory task, but due to its functional nature, also entail the translation of experienced episodes into semantic rules acquired by training. PMID- 26834596 TI - Extinction and Retrieval + Extinction of Conditioned Fear Differentially Activate Medial Prefrontal Cortex and Amygdala in Rats. AB - Pairing a previously neutral conditioned stimulus (CS; e.g., a tone) to an aversive unconditioned stimulus (US; e.g., a footshock) leads to associative learning such that the tone alone comes to elicit a conditioned response (e.g., freezing). We have previously shown that an extinction session that occurs within the reconsolidation window (termed retrieval + extinction) attenuates fear responding and prevents the return of fear in Pavlovian fear conditioning (Monfils et al., 2009). To date, the mechanisms that explain the different behavioral outcomes between standard extinction and retrieval + extinction remain poorly understood. Here we sought to examine the differential temporal engagement of specific neural systems by these two approaches using Arc catFISH (cellular compartment analysis of temporal activity using fluorescence in situ hybridization (FISH)). Our results demonstrate that extinction and retrieval + extinction lead to differential patterns of expression, suggesting that they engage different networks. These findings provide insight into the neural mechanisms that allow extinction during reconsolidation to prevent the return of fear in rodents. PMID- 26834597 TI - Measuring Attention in Rodents: Comparison of a Modified Signal Detection Task and the 5-Choice Serial Reaction Time Task. AB - Neuropsychiatric research has utilized cognitive testing in rodents to improve our understanding of cognitive deficits and for preclinical drug development. However, more sophisticated cognitive tasks have not been as widely exploited due to low throughput and the extensive training time required. We developed a modified signal detection task (SDT) based on the growing body of literature aimed at improving cognitive testing in rodents. This study directly compares performance on the modified SDT with a traditional test for measuring attention, the 5-choice serial reaction time task (5CSRTT). Adult male Sprague-Dawley rats were trained on either the 5CSRTT or the SDT. Briefly, the 5CSRTT required rodents to pay attention to a spatial array of five apertures and respond with a nose poke when an aperture was illuminated. The SDT required the rat to attend to a light panel and respond either left or right to indicate the presence of a signal. In addition, modifications were made to the reward delivery, timing, control of body positioning, and the self-initiation of trials. It was found that less training time was required for the SDT, with both sessions to criteria and daily session duration significantly reduced. Rats performed with a high level of accuracy (>87%) on both tasks, however omissions were far more frequent on the 5CSRTT. The signal duration was reduced on both tasks as a manipulation of task difficulty relevant to attention and a similar pattern of decreasing accuracy was observed on both tasks. These results demonstrate some of the advantages of the SDT over the traditional 5CSRTT as being higher throughput with reduced training time, fewer omission responses and their body position was controlled at stimulus onset. In addition, rats performing the SDT had comparable high levels of accuracy. These results highlight the differences and similarities between the 5CSRTT and a modified SDT as tools for assessing attention in preclinical animal models. PMID- 26834598 TI - Neural Processing of Calories in Brain Reward Areas Can be Modulated by Reward Sensitivity. AB - A food's reward value is dependent on its caloric content. Furthermore, a food's acute reward value also depends on hunger state. The drive to obtain rewards (reward sensitivity), however, differs between individuals. Here, we assessed the association between brain responses to calories in the mouth and trait reward sensitivity in different hunger states. Firstly, we assessed this in data from a functional neuroimaging study (van Rijn et al., 2015), in which participants (n = 30) tasted simple solutions of a non-caloric sweetener with or without a non sweet carbohydrate (maltodextrin) during hunger and satiety. Secondly, we expanded these analyses to regular drinks by assessing the same relationship in data from a study in which soft drinks sweetened with either sucrose or a non caloric sweetener were administered during hunger (n = 18) (Griffioen-Roose et al., 2013). First, taste activation by the non-caloric solution/soft drink was subtracted from that by the caloric solution/soft drink to eliminate sweetness effects and retain activation induced by calories. Subsequently, this difference in taste activation was correlated with reward sensitivity as measured with the BAS drive subscale of the Behavioral Activation System (BAS) questionnaire. When participants were hungry and tasted calories from the simple solution, brain activation in the right ventral striatum (caudate), right amygdala and anterior cingulate cortex (bilaterally) correlated negatively with BAS drive scores. In contrast, when participants were satiated, taste responses correlated positively with BAS drive scores in the left caudate. These results were not replicated for soft drinks. Thus, neural responses to oral calories from maltodextrin were modulated by reward sensitivity in reward-related brain areas. This was not the case for sucrose. This may be due to the direct detection of maltodextrin, but not sucrose in the oral cavity. Also, in a familiar beverage, detection of calories per se may be overruled by a conditioned response to its flavor. In conclusion, the brain reward response to calories from a long chain starch sugar (maltodextrin) varies with trait reward sensitivity. The absence of this effect in a familiar beverage warrants further research into its relevance for real life ingestive behavior. PMID- 26834599 TI - Involvement of Dopamine D1/D5 and D2 Receptors in Context-Dependent Extinction Learning and Memory Reinstatement. AB - Dopamine contributes to the regulation of higher order information processing and executive control. It is important for memory consolidation processes, and for the adaptation of learned responses based on experience. In line with this, under aversive learning conditions, application of dopamine receptor antagonists prior to extinction result in enhanced memory reinstatement. Here, we investigated the contribution of the dopaminergic system to extinction and memory reinstatement (renewal) of an appetitive spatial learning task in rodents. Rats were trained for 3 days in a T-maze (context "A") to associate a goal arm with a food reward, despite low reward probability (acquisition phase). On day 4, extinction learning (unrewarded) occurred, that was reinforced by a context change ("B"). On day 5, re-exposure to the (unrewarded) "A" context took place (renewal of context "A", followed by extinction of context "A"). In control animals, significant extinction occurred on day 4, that was followed by an initial memory reinstatement (renewal) on day 5, that was, in turn, succeeded by extinction of renewal. Intracerebral treatment with a D1/D5-receptor antagonist prior to the extinction trials, elicited a potent enhancement of extinction in context "B". By contrast, a D1/D5-agonist impaired renewal in context "A". Extinction in the "A" context on day 5 was unaffected by the D1/D5-ligands. Treatment with a D2 receptor antagonist prior to extinction had no overall effect on extinction in context "B" or renewal in context "A", although extinction of the renewal effect was impaired on day 5, compared to controls. Taken together, these data suggest that dopamine acting on the D1/D5-receptor modulates both acquisition and consolidation of context-dependent extinction. By contrast, the D2-receptor may contribute to context-independent aspects of this kind of extinction learning. PMID- 26834600 TI - Intrinsic Functional Plasticity of the Thalamocortical System in Minimally Disabled Patients with Relapsing-Remitting Multiple Sclerosis. AB - The thalamus plays a crucial role in sensorimotor, cognitive, and attentional circuit functions. Disruptions in thalamic connectivity are believed to underlie the symptoms of multiple sclerosis (MS). Therefore, assessing thalamocortical structural connectivity (SC) and functional connectivity (FC) may provide new insights into the mechanism of intrinsic functional plasticity in a large-scale neural network. We used resting-state FC measurement and diffusion tensor imaging probabilistic tractography to study the functional and structural integrity of the thalamocortical system in patients with relapsing-remitting MS (RRMS) and matched healthy controls. In the thalamocortical connections of RRMS patients, we found lesion load-related regional FC in the right temporal pole, which reflected compensatory hyperconnectivity related to lesion-related demyelination. We also found significant correlations between increased diffusivity and slowed cognitive processing (PASAT) or the impact of fatigue (MFIS-5), as well as between connective fiber loss and disease duration. Taken together, the evidence from SC and FC analysis of the thalamocortical system suggests that minimally disabled RRMS patients exhibit a dissociated SC-FC pattern and limited regional functional plasticity to compensate for the chronic demyelination-related loss of long distance SC. These results also provide further evidence supporting the notion that MS is a disorder of anatomical disconnection. PMID- 26834604 TI - Commentary: Cultural differences in on-line sensitivity to emotional voices: comparing East and West. PMID- 26834603 TI - Alteration of Political Belief by Non-invasive Brain Stimulation. AB - People generally have imperfect introspective access to the mechanisms underlying their political beliefs, yet can confidently communicate the reasoning that goes into their decision making process. An innate desire for certainty and security in ones beliefs may play an important and somewhat automatic role in motivating the maintenance or rejection of partisan support. The aim of the current study was to clarify the role of the DLPFC in the alteration of political beliefs. Recent neuroimaging studies have focused on the association between the DLPFC (a region involved in the regulation of cognitive conflict and error feedback processing) and reduced affiliation with opposing political candidates. As such, this study used a method of non-invasive brain simulation (tRNS) to enhance activity of the bilateral DLPFC during the incorporation of political campaign information. These findings indicate a crucial role for this region in political belief formation. However, enhanced activation of DLPFC does not necessarily result in the specific rejection of political beliefs. In contrast to the hypothesis the results appear to indicate a significant increase in conservative values regardless of participant's initial political orientation and the political campaign advertisement they were exposed to. PMID- 26834601 TI - Top-Down Control of Visual Alpha Oscillations: Sources of Control Signals and Their Mechanisms of Action. AB - Alpha oscillations (8-12 Hz) are thought to inversely correlate with cortical excitability. Goal-oriented modulation of alpha has been studied extensively. In visual spatial attention, alpha over the region of visual cortex corresponding to the attended location decreases, signifying increased excitability to facilitate the processing of impending stimuli. In contrast, in retention of verbal working memory, alpha over visual cortex increases, signifying decreased excitability to gate out stimulus input to protect the information held online from sensory interference. According to the prevailing model, this goal-oriented biasing of sensory cortex is effected by top-down control signals from frontal and parietal cortices. The present study tests and substantiates this hypothesis by (a) identifying the signals that mediate the top-down biasing influence, (b) examining whether the cortical areas issuing these signals are task-specific or task-independent, and (c) establishing the possible mechanism of the biasing action. High-density human EEG data were recorded in two experimental paradigms: a trial-by-trial cued visual spatial attention task and a modified Sternberg working memory task. Applying Granger causality to both sensor-level and source level data we report the following findings. In covert visual spatial attention, the regions exerting top-down control over visual activity are lateralized to the right hemisphere, with the dipoles located at the right frontal eye field (FEF) and the right inferior frontal gyrus (IFG) being the main sources of top-down influences. During retention of verbal working memory, the regions exerting top down control over visual activity are lateralized to the left hemisphere, with the dipoles located at the left middle frontal gyrus (MFG) being the main source of top-down influences. In both experiments, top-down influences are mediated by alpha oscillations, and the biasing effect is likely achieved via an inhibition disinhibition mechanism. PMID- 26834605 TI - Mirror Visual Feedback-Induced Performance Improvement and the Influence of Hand Dominance. AB - Mirror visual feedback (MVF) is a promising technique in clinical settings that can be used to augment performance of an untrained limb. Several studies with healthy volunteers and patients using transcranial magnetic stimulation (TMS) or functional magnetic resonance imaging (fMRI) indicate that functional alterations within primary motor cortex (M1) might be one candidate mechanism that could explain MVF-induced changes in behavior. Until now, most studies have used MVF to improve performance of the non-dominant hand (NDH). The question remains if the behavioral effect of MVF differs according to hand dominance. Here, we conducted a study with two groups of young, healthy right-handed volunteers who performed a complex ball-rotation task while receiving MVF of the dominant (n = 16, group 1, MVFDH) or NDH (n = 16, group 2, MVFNDH). We found no significant differences in baseline performance of the untrained hand between groups before MVF was applied. Furthermore, there was no significant difference in the amount of performance improvement between MVFDH and MVFNDH indicating that the outcome of MVF seems not to be influenced by hand dominance. Thus our findings might have important implications in neurorehabilitation suggesting that patients suffering from unilateral motor impairments might benefit from MVF regardless of the dominance of the affected limb. PMID- 26834602 TI - Endurance Exercise as an "Endogenous" Neuro-enhancement Strategy to Facilitate Motor Learning. AB - Endurance exercise improves cardiovascular and musculoskeletal function and may also increase the information processing capacities of the brain. Animal and human research from the past decade demonstrated widespread exercise effects on brain structure and function at the systems-, cellular-, and molecular level of brain organization. These neurobiological mechanisms may explain the well established positive influence of exercise on performance in various behavioral domains but also its contribution to improved skill learning and neuroplasticity. With respect to the latter, only few empirical and theoretical studies are available to date. The aim of this review is (i) to summarize the existing neurobiological and behavioral evidence arguing for endurance exercise-induced improvements in motor learning and (ii) to develop hypotheses about the mechanistic link between exercise and improved learning. We identify major knowledge gaps that need to be addressed by future research projects to advance our understanding of how exercise should be organized to optimize motor learning. PMID- 26834607 TI - Processing Functional Near Infrared Spectroscopy Signal with a Kalman Filter to Assess Working Memory during Simulated Flight. AB - Working memory (WM) is a key executive function for operating aircraft, especially when pilots have to recall series of air traffic control instructions. There is a need to implement tools to monitor WM as its limitation may jeopardize flight safety. An innovative way to address this issue is to adopt a Neuroergonomics approach that merges knowledge and methods from Human Factors, System Engineering, and Neuroscience. A challenge of great importance for Neuroergonomics is to implement efficient brain imaging techniques to measure the brain at work and to design Brain Computer Interfaces (BCI). We used functional near infrared spectroscopy as it has been already successfully tested to measure WM capacity in complex environment with air traffic controllers (ATC), pilots, or unmanned vehicle operators. However, the extraction of relevant features from the raw signal in ecological environment is still a critical issue due to the complexity of implementing real-time signal processing techniques without a priori knowledge. We proposed to implement the Kalman filtering approach, a signal processing technique that is efficient when the dynamics of the signal can be modeled. We based our approach on the Boynton model of hemodynamic response. We conducted a first experiment with nine participants involving a basic WM task to estimate the noise covariances of the Kalman filter. We then conducted a more ecological experiment in our flight simulator with 18 pilots who interacted with ATC instructions (two levels of difficulty). The data was processed with the same Kalman filter settings implemented in the first experiment. This filter was benchmarked with a classical pass-band IIR filter and a Moving Average Convergence Divergence (MACD) filter. Statistical analysis revealed that the Kalman filter was the most efficient to separate the two levels of load, by increasing the observed effect size in prefrontal areas involved in WM. In addition, the use of a Kalman filter increased the performance of the classification of WM levels based on brain signal. The results suggest that Kalman filter is a suitable approach for real-time improvement of near infrared spectroscopy signal in ecological situations and the development of BCI. PMID- 26834606 TI - Fear and Reward Circuit Alterations in Pediatric CRPS. AB - In chronic pain, a number of brain regions involved in emotion (e.g., amygdala, hippocampus, nucleus accumbens, insula, anterior cingulate, and prefrontal cortex) show significant functional and morphometric changes. One phenotypic manifestation of these changes is pain-related fear (PRF). PRF is associated with profoundly altered behavioral adaptations to chronic pain. For example, patients with a neuropathic pain condition known as complex regional pain syndrome (CRPS) often avoid use of and may even neglect the affected body area(s), thus maintaining and likely enhancing PRF. These changes form part of an overall maladaptation to chronic pain. To examine fear-related brain circuit alterations in humans, 20 pediatric patients with CRPS and 20 sex- and age-matched healthy controls underwent functional magnetic resonance imaging (fMRI) in response to a well-established fearful faces paradigm. Despite no significant differences on self-reported emotional valence and arousal between the two groups, CRPS patients displayed a diminished response to fearful faces in regions associated with emotional processing compared to healthy controls. Additionally, increased PRF levels were associated with decreased activity in a number of brain regions including the right amygdala, insula, putamen, and caudate. Blunted activation in patients suggests that (a) individuals with chronic pain may have deficits in cognitive-affective brain circuits that may represent an underlying vulnerability or consequence to the chronic pain state; and (b) fear of pain may contribute and/or maintain these brain alterations. Our results shed new light on altered affective circuits in patients with chronic pain and identify PRF as a potentially important treatment target. PMID- 26834609 TI - Neural Correlates of Morphological Processing: Evidence from Chinese. AB - Morphological decomposition is an important part of complex word processing. In Chinese, this requires a comprehensive consideration of phonological, orthographic and morphemic information. The left inferior frontal gyrus (L-IFG) has been implicated in this process in alphabetic languages. However, it is unclear whether the neural mechanisms underlying morphological processing in alphabetic languages would be the same in Chinese, a logographic language. To investigate the neural basis of morphological processing in Chinese compound words, an fMRI experiment was conducted using an explicit auditory morphological judgment task. Results showed the L-IFG to be a core area in Chinese morphological processing, consistent with research in alphabetic languages. Additionally, a broad network consisting of the L-MTG, the bilateral STG and the L-FG that taps phonological, orthographic, and semantic information was found to be involved. These results provide evidence that the L-IFG plays an important role in morphological processing even in languages that are typologically different. PMID- 26834610 TI - Balance Impairments after Brachial Plexus Injury as Assessed through Clinical and Posturographic Evaluation. AB - OBJECTIVE: To investigate whether a sensorimotor deficit of the upper limb following a brachial plexus injury (BPI) affects the upright balance. DESIGN: Eleven patients with a unilateral BPI and 11 healthy subjects were recruited. The balance assessment included the Berg Balance Scale (BBS), the number of feet touches on the ground while performing a 60 s single-leg stance and posturographic assessment (eyes open and feet placed hip-width apart during a single 60 s trial). The body weight distribution (BWD) between the legs was estimated from the center of pressure (COP) lateral position. The COP variability was quantified in the anterior-posterior and lateral directions. RESULTS: BPI patients presented lower BBS scores (p = 0.048) and a higher frequency of feet touches during the single-leg stance (p = 0.042) compared with those of the healthy subjects. An asymmetric BWD toward the side opposite the affected arm was shown by 73% of BPI patients. Finally, higher COP variability was observed in BPI patients compared with healthy subjects for anterior-posterior (p = 0.020), but not for lateral direction (p = 0.818). CONCLUSIONS: This study demonstrates that upper limb sensorimotor deficits following BPI affect body balance, serving as a warning for the clinical community about the need to prevent and treat the secondary outcomes of this condition. PMID- 26834611 TI - Steady-State Somatosensory Evoked Potential for Brain-Computer Interface-Present and Future. AB - Brain-computer interface (BCI) performance has achieved continued improvement over recent decades, and sensorimotor rhythm-based BCIs that use motor function have been popular subjects of investigation. However, it remains problematic to introduce them to the public market because of their low reliability. As an alternative resolution to this issue, visual-based BCIs that use P300 or steady state visually evoked potentials (SSVEPs) seem promising; however, the inherent visual fatigue that occurs with these BCIs may be unavoidable. For these reasons, steady-state somatosensory evoked potential (SSSEP) BCIs, which are based on tactile selective attention, have gained increasing attention recently. These may reduce the fatigue induced by visual attention and overcome the low reliability of motor activity. In this literature survey, recent findings on SSSEP and its methodological uses in BCI are reviewed. Further, existing limitations of SSSEP BCI and potential future directions for the technique are discussed. PMID- 26834612 TI - ERP Correlates of Verbal and Numerical Probabilities in Risky Choices: A Two Stage Probability Processing View. AB - Two kinds of probability expressions, verbal and numerical, have been used to characterize the uncertainty that people face. However, the question of whether verbal and numerical probabilities are cognitively processed in a similar manner remains unresolved. From a levels-of-processing perspective, verbal and numerical probabilities may be processed differently during early sensory processing but similarly in later semantic-associated operations. This event-related potential (ERP) study investigated the neural processing of verbal and numerical probabilities in risky choices. The results showed that verbal probability and numerical probability elicited different N1 amplitudes but that verbal and numerical probabilities elicited similar N2 and P3 waveforms in response to different levels of probability (high to low). These results were consistent with a levels-of-processing framework and suggest some internal consistency between the cognitive processing of verbal and numerical probabilities in risky choices. Our findings shed light on possible mechanism underlying probability expression and may provide the neural evidence to support the translation of verbal to numerical probabilities (or vice versa). PMID- 26834608 TI - Multi-Dimensional Dynamics of Human Electromagnetic Brain Activity. AB - Magnetoencephalography (MEG) and electroencephalography (EEG) are invaluable neuroscientific tools for unveiling human neural dynamics in three dimensions (space, time, and frequency), which are associated with a wide variety of perceptions, cognition, and actions. MEG/EEG also provides different categories of neuronal indices including activity magnitude, connectivity, and network properties along the three dimensions. In the last 20 years, interest has increased in inter-regional connectivity and complex network properties assessed by various sophisticated scientific analyses. We herein review the definition, computation, short history, and pros and cons of connectivity and complex network (graph-theory) analyses applied to MEG/EEG signals. We briefly describe recent developments in source reconstruction algorithms essential for source-space connectivity and network analyses. Furthermore, we discuss a relatively novel approach used in MEG/EEG studies to examine the complex dynamics represented by human brain activity. The correct and effective use of these neuronal metrics provides a new insight into the multi-dimensional dynamics of the neural representations of various functions in the complex human brain. PMID- 26834613 TI - The Brain Mechanisms Underlying the Perception of Pungent Taste of Capsaicin and the Subsequent Autonomic Responses. AB - In a human fMRI study, it has been demonstrated that tasting and ingesting capsaicin activate the ventral part of the middle and posterior short gyri (M/PSG) of the insula which is known as the primary gustatory area, suggesting that capsaicin is recognized as a taste. Tasting and digesting spicy foods containing capsaicin induce various physiological responses such as perspiration from face, salivation, and facilitation of cardiovascular activity, which are thought to be caused through viscero-visceral autonomic reflexes. However, this does not necessarily exclude the possibility of the involvement of higher-order sensory-motor integration between the M/PSG and anterior short gyrus (ASG) known as the autonomic region of the insula. To reveal a possible functional coordination between the M/PSG and ASG, we here addressed whether capsaicin increases neural activity in the ASG as well as the M/PSG using fMRI and a custom made taste delivery system. Twenty subjects participated in this study, and three tastant solutions: capsaicin, NaCl, and artificial saliva (AS) were used. Group analyses with the regions activated by capsaicin revealed significant activations in the bilateral ASG and M/PSG. The fMRI blood oxygenation level-dependent (BOLD) signals in response to capsaicin stimulation were significantly higher in ASG than in M/PSG regardless of the side. Concomitantly, capsaicin increased the fingertip temperature significantly. Although there was no significant correlation between the fingertip temperatures and BOLD signals in the ASG or M/PSG when the contrast [Capsaicin-AS] or [Capsaicin-NaCl] was computed, a significant correlation was found in the bilateral ASG when the contrast [2 * Capsaicin-NaCl-AS] was computed. In contrast, there was a significant correlation in the hypothalamus regardless of the contrasts. Furthermore, there was a significant correlation between M/PSG and ASG. These results indicate that capsaicin increases neural activity in the ASG as well as the M/PSG, suggesting that the neural coordination between the two cortical areas may be involved in autonomic responses to tasting spicy foods as reflected in fingertip temperature increases. PMID- 26834614 TI - Lesions to Lateral Prefrontal Cortex Impair Lexical Interference Control in Word Production. AB - Speaking is an action that requires control, for example, to prevent interference from distracting or competing information present in the speaker's environment. Control over task performance is thought to depend on the lateral prefrontal cortex (PFC). However, the neuroimaging literature does not show a consistent relation between left PFC and interference control in word production. Here, we examined the role of left PFC in interference control in word production by testing six patients with lesions to left PFC (centered around the ventrolateral PFC) on a control-demanding task. Patients and age-matched controls named pictures presented along with distractor words, inducing within-trial interference effects. We varied the degree of competing information from distractors to increase the need for interference control. Distractors were semantically related, phonologically related, unrelated to the picture name, or neutral (XXX). Both groups showed lexical interference (slower responses with unrelated than neutral distractors), reflecting naming difficulty in the presence of competing linguistic information. Relative to controls, all six left PFC patients had larger lexical interference effects. By contrast, patients did not show a consistent semantic interference effect (reflecting difficulty in selecting amongst semantic competitors) whereas the controls did. This suggests different control mechanisms may be engaged in semantic compared to lexical interference resolution in this paradigm. Finally, phonological facilitation (faster responses with phonological than unrelated distractors) was larger in patients than in controls. These findings suggest that the lateral PFC is a necessary structure in providing control over lexical interference in word production, possibly through an early attentional blocking mechanism. By contrast, the left PFC does not seem critical in semantic interference resolution in the picture-word interference paradigm. PMID- 26834615 TI - Relative Power of Specific EEG Bands and Their Ratios during Neurofeedback Training in Children with Autism Spectrum Disorder. AB - Neurofeedback is a mode of treatment that is potentially useful for improving self-regulation skills in persons with autism spectrum disorder. We proposed that operant conditioning of EEG in neurofeedback mode can be accompanied by changes in the relative power of EEG bands. However, the details on the change of the relative power of EEG bands during neurofeedback training course in autism are not yet well explored. In this study, we analyzed the EEG recordings of children diagnosed with autism and enrolled in a prefrontal neurofeedback treatment course. The protocol used in this training was aimed at increasing the ability to focus attention, and the procedure represented the wide band EEG amplitude suppression training along with upregulation of the relative power of gamma activity. Quantitative EEG analysis was completed for each session of neurofeedback using wavelet transform to determine the relative power of gamma and theta/beta ratio, and further to detect the statistical changes within and between sessions. We found a linear decrease of theta/beta ratio and a liner increase of relative power of gamma activity over 18 weekly sessions of neurofeedback in 18 high functioning children with autism. The study indicates that neurofeedback is an effective method for altering EEG characteristics associated with the autism spectrum disorder. Also, it provides information about specific changes of EEG activities and details the correlation between changes of EEG and neurofeedback indexes during the course of neurofeedback. This pilot study contributes to the development of more effective approaches to EEG data analysis during prefrontal neurofeedback training in autism. PMID- 26834616 TI - Functional and Topological Conditions for Explosive Synchronization Develop in Human Brain Networks with the Onset of Anesthetic-Induced Unconsciousness. AB - Sleep, anesthesia, and coma share a number of neural features but the recovery profiles are radically different. To understand the mechanisms of reversibility of unconsciousness at the network level, we studied the conditions for gradual and abrupt transitions in conscious and anesthetized states. We hypothesized that the conditions for explosive synchronization (ES) in human brain networks would be present in the anesthetized brain just over the threshold of unconsciousness. To test this hypothesis, functional brain networks were constructed from multi channel electroencephalogram (EEG) recordings in seven healthy subjects across conscious, unconscious, and recovery states. We analyzed four variables that are involved in facilitating ES in generic, non-biological networks: (1) correlation between node degree and frequency, (2) disassortativity (i.e., the tendency of highly-connected nodes to link with less-connected nodes, or vice versa), (3) frequency difference of coupled nodes, and (4) an inequality relationship between local and global network properties, which is referred to as the suppressive rule. We observed that the four network conditions for ES were satisfied in the unconscious state. Conditions for ES in the human brain suggest a potential mechanism for rapid recovery from the lightly-anesthetized state. This study demonstrates for the first time that the network conditions for ES, formerly shown in generic networks only, are present in empirically-derived functional brain networks. Further investigations with deep anesthesia, sleep, and coma could provide insight into the underlying causes of variability in recovery profiles of these unconscious states. PMID- 26834617 TI - A Phenomenological Synapse Model for Asynchronous Neurotransmitter Release. AB - Neurons communicate with each other via synapses. Action potentials cause release of neurotransmitters at the axon terminal. Typically, this neurotransmitter release is tightly time-locked to the arrival of an action potential and is thus called synchronous release. However, neurotransmitter release is stochastic and the rate of release of small quanta of neurotransmitters can be considerably elevated even long after the ceasing of spiking activity, leading to asynchronous release of neurotransmitters. Such asynchronous release varies for tissue and neuron types and has been shown recently to be pronounced in fast-spiking neurons. Notably, it was found that asynchronous release is enhanced in human epileptic tissue implicating a possibly important role in generating abnormal neural activity. Current neural network models for simulating and studying neural activity virtually only consider synchronous release and ignore asynchronous transmitter release. Here, we develop a phenomenological model for asynchronous neurotransmitter release, which, on one hand, captures the fundamental features of the asynchronous release process, and, on the other hand, is simple enough to be incorporated in large-size network simulations. Our proposed model is based on the well-known equations for short-term dynamical synaptic interactions and includes an additional stochastic term for modeling asynchronous release. We use experimental data obtained from inhibitory fast-spiking synapses of human epileptic tissue to fit the model parameters, and demonstrate that our model reproduces the characteristics of realistic asynchronous transmitter release. PMID- 26834618 TI - An Assessment of Six Muscle Spindle Models for Predicting Sensory Information during Human Wrist Movements. AB - BACKGROUND: The muscle spindle is an important sensory organ for proprioceptive information, yet there have been few attempts to use Shannon information theory to quantify the capacity of human muscle spindles to encode sensory input. METHODS: Computer simulations linked kinematics, to biomechanics, to six muscle spindle models that generated predictions of firing rate. The predicted firing rates were compared to firing rates of human muscle spindles recorded during a step-tracking (center-out) task to validate their use. The models were then used to predict firing rates during random movements with statistical properties matched to the ergonomics of human wrist movements. The data were analyzed for entropy and mutual information. RESULTS: Three of the six models produced predictions that approximated the firing rate of human spindles during the step tracking task. For simulated random movements these models predicted mean rates of 16.0 +/- 4.1 imp/s (mean +/- SD), peak firing rates <50 imp/s and zero firing rate during an average of 25% of the movement. The average entropy of the neural response was 4.1 +/- 0.3 bits and is an estimate of the maximum information that could be carried by muscles spindles during ecologically valid movements. The information about tendon displacement preserved in the neural response was 0.10 +/- 0.05 bits per symbol; whereas 1.25 +/- 0.30 bits per symbol of velocity input were preserved in the neural response of the spindle models. CONCLUSIONS: Muscle spindle models, originally based on cat experiments, have predictive value for modeling responses of human muscle spindles with minimal parameter optimization. These models predict more than 10-fold more velocity over length information encoding during ecologically valid movements. These results establish theoretical parameters for developing neuroprostheses for proprioceptive function. PMID- 26834619 TI - Contextual Modulation is Related to Efficiency in a Spiking Network Model of Visual Cortex. AB - In the visual cortex, stimuli outside the classical receptive field (CRF) modulate the neural firing rate, without driving the neuron by themselves. In the primary visual cortex (V1), such contextual modulation can be parametrized with an area summation function (ASF): increasing stimulus size causes first an increase and then a decrease of firing rate before reaching an asymptote. Earlier work has reported increase of sparseness when CRF stimulation is extended to its surroundings. However, there has been no clear connection between the ASF and network efficiency. Here we aimed to investigate possible link between ASF and network efficiency. In this study, we simulated the responses of a biomimetic spiking neural network model of the visual cortex to a set of natural images. We varied the network parameters, and compared the V1 excitatory neuron spike responses to the corresponding responses predicted from earlier single neuron data from primate visual cortex. The network efficiency was quantified with firing rate (which has direct association to neural energy consumption), entropy per spike and population sparseness. All three measures together provided a clear association between the network efficiency and the ASF. The association was clear when varying the horizontal connectivity within V1, which influenced both the efficiency and the distance to ASF, DAS. Given the limitations of our biophysical model, this association is qualitative, but nevertheless suggests that an ASF like receptive field structure can cause efficient population response. PMID- 26834620 TI - Generalized Laminar Population Analysis (gLPA) for Interpretation of Multielectrode Data from Cortex. AB - Laminar population analysis (LPA) is a method for analysis of electrical data recorded by linear multielectrodes passing through all lamina of cortex. Like principal components analysis (PCA) and independent components analysis (ICA), LPA offers a way to decompose the data into contributions from separate cortical populations. However, instead of using purely mathematical assumptions in the decomposition, LPA is based on physiological constraints, i.e., that the observed LFP (low-frequency part of signal) is driven by action-potential firing as observed in the MUA (multi-unit activity; high-frequency part of the signal). In the presently developed generalized laminar population analysis (gLPA) the set of basis functions accounting for the LFP data is extended compared to the original LPA, thus allowing for a better fit of the model to experimental data. This enhances the risk for overfitting, however, and we therefore tested various versions of gLPA on virtual LFP data in which we knew the ground truth. These synthetic data were generated by biophysical forward-modeling of electrical signals from network activity in the comprehensive, and well-known, thalamocortical network model developed by Traub and coworkers. The results for the Traub model imply that while the laminar components extracted by the original LPA method overall are in fair agreement with the ground-truth laminar components, the results may be improved by use of gLPA method with two (gLPA-2) or even three (gLPA-3) postsynaptic LFP kernels per laminar population. PMID- 26834621 TI - The Amyloid Precursor Protein-A Novel Player within the Molecular Array of Presynaptic Nanomachines. AB - More than 20 years ago the amyloid precursor protein (APP) was identified as the precursor protein of the Abeta peptide, the main component of senile plaques in brains affected by Alzheimer's disease (AD). The pathophysiology of AD, characterized by a massive loss of synapses, cognitive decline, and behavioral changes was in principle attributed to the accumulation of Abeta. Within the last decades, much effort has gone into understanding the molecular basis of the progression of AD. However, little is known about the actual physiological function of APPs. Allocating APP to the proteome of the structurally and functionally dynamic presynaptic active zone (PAZ) highlights APP as a hitherto unknown player within the setting of the presynapse. The molecular array of presynaptic nanomachines comprising the life cycle of synaptic vesicles, exo- and endocytosis, cytoskeletal rearrangements, and mitochondrial activity provides a balance between structural and functional maintenance and diversity. The generation of genetically designed mouse models further deciphered APP as an essential player in synapse formation and plasticity. Deletion of APP causes an age-dependent phenotype: while younger mice revealed almost no physiological impairments, this condition was changed in the elderly mice. Interestingly, the proteomic composition of neurotransmitter release sites already revealed substantial changes at young age. These changes point to a network that incorporates APP into a cluster of nanomachines. Currently, the underlying mechanism of how APP acts within these machines is still elusive. Within the scope of this review, we shall construct a network of APP interaction partners within the PAZ. Furthermore, we intend to outline how deletion of APP affects this network during space and time leading to impairments in learning and memory. These alterations may provide a molecular link to the pathogenesis of AD and the physiological function of APP in the central nervous system. PMID- 26834622 TI - Magnetic Resonance Q Mapping Reveals a Decrease in Microvessel Density in the arcAbeta Mouse Model of Cerebral Amyloidosis. AB - Alterations in density and morphology of the cerebral microvasculature have been reported to occur in Alzheimer's disease patients and animal models of the disease. In this study we compared magnetic resonance imaging (MRI) techniques for their utility to detect age-dependent changes of the cerebral vasculature in the arcAbeta mouse model of cerebral amyloidosis. Dynamic susceptibility contrast (DSC)-MRI was performed by tracking the passage of a superparamagnetic iron oxide nanoparticle in the brain with dynamic gradient echo planar imaging (EPI). From this measurements relative cerebral blood volume [rCBV(DSC)] and relative cerebral blood flow (rCBF) were estimated. For the same animal maps of the relaxation shift index Q were computed from high resolution gradient echo and spin echo data that were acquired before and after superparamagnetic iron oxide (SPIO) nanoparticle injection. Q-values were used to derive estimates of microvessel density. The change in the relaxation rates [Formula: see text] obtained from pre- and post-contrast gradient echo data was used for the alternative determination of rCBV [rCBV([Formula: see text])]. Linear mixed effects modeling found no significant association between rCBV(DSC), rCBV([Formula: see text]), rCBF, and Q with genotype in 13-month old mice [compared to age-matched non-transgenic littermates (NTLs)] for any of the evaluated brain regions. In 24-month old mice there was a significant association for rCBV(DSC) with genotype in the cerebral cortex, and for rCBV([Formula: see text]) in the cerebral cortex and cerebellum. For rCBF there was a significant association in the cerebellum but not in other brain regions. Q-values in the olfactory bulb, cerebral cortex, striatum, hippocampus, and cerebellum in 24 month old mice were significantly associated with genotype. In those regions Q values were reduced between 11 and 26% in arcAbeta mice compared to age-matched NTLs. Vessel staining with CD31 immunohistochemistry confirmed a reduction of microvessel density in the old arcAbeta mice. We further demonstrated a region specific association between parenchymal and vascular deposition of beta-amyloid and decreased vascular density, without a correlation with the amount of Abeta deposition. We found that Q mapping was more suitable than the hemodynamic read outs to detect amyloid-related degeneration of the cerebral microvasculature. PMID- 26834623 TI - Age Differences in Prefrontal Surface Area and Thickness in Middle Aged to Older Adults. AB - Age is associated with reductions in surface area and cortical thickness, particularly in prefrontal regions. There is also evidence of greater thickness in some regions at older ages. Non-linear age effects in some studies suggest that age may continue to impact brain structure in later decades of life, but relatively few studies have examined the impact of age on brain structure within middle-aged to older adults. We investigated age differences in prefrontal surface area and cortical thickness in healthy adults between the ages of 51 and 81 years. Participants received a structural 3-Tesla magnetic resonance imaging scan. Based on a priori hypotheses, primary analyses focused on surface area and cortical thickness in the dorsolateral prefrontal cortex, anterior cingulate cortex, and orbitofrontal cortex. We also performed exploratory vertex-wise analyses of surface area and cortical thickness across the entire cortex. We found that older age was associated with smaller surface area in the dorsolateral prefrontal and orbitofrontal cortices but greater cortical thickness in the dorsolateral prefrontal and anterior cingulate cortices. Vertex-wise analyses revealed smaller surface area in primarily frontal regions at older ages, but no age effects were found for cortical thickness. Results suggest age is associated with reduced surface area but greater cortical thickness in prefrontal regions during later decades of life, and highlight the differential effects age has on regional surface area and cortical thickness. PMID- 26834624 TI - Effects of Long-Term Mindfulness Meditation on Brain's White Matter Microstructure and its Aging. AB - Although research on the effects of mindfulness meditation (MM) is increasing, still very little has been done to address its influence on the white matter (WM) of the brain. We hypothesized that the practice of MM might affect the WM microstructure adjacent to five brain regions of interest associated with mindfulness. Diffusion tensor imaging was employed on samples of meditators and non-meditators (n = 64) in order to investigate the effects of MM on group difference and aging. Tract-Based Spatial Statistics was used to estimate the fractional anisotrophy of the WM connected to the thalamus, insula, amygdala, hippocampus, and anterior cingulate cortex. The subsequent generalized linear model analysis revealed group differences and a group-by-age interaction in all five selected regions. These data provide preliminary indications that the practice of MM might result in WM connectivity change and might provide evidence on its ability to help diminish age-related WM degeneration in key regions which participate in processes of mindfulness. PMID- 26834626 TI - Age-Related Changes in Dynamic Postural Control and Attentional Demands are Minimally Affected by Local Muscle Fatigue. AB - Normal aging results in alterations in the visual, vestibular and somtaosensory systems, which in turn modify the control of balance. Muscle fatigue may exacerbate these age-related changes in sensory and motor functions, and also increase the attentional demands associated with dynamic postural control. The purpose of this study was to investigate the effect of aging on dynamic postural control and posture-related attentional demands before and after a plantar flexor fatigue protocol. Participants (young adults: n = 15; healthy seniors: n = 13) performed a dynamic postural task along the antero-posterior (AP) and the medio lateral (ML) axes, with and without the addition of a simple reaction time (RT) task. The dynamic postural task consisted in following a moving circle on a computer screen with the representation of the center of pressure (COP). This protocol was repeated before and after a fatigue task where ankle plantar flexor muscles were targeted. The mean COP-target distance and the mean COP velocity were calculated for each trial. Cross-correlation analyses between the COP and target displacements were also performed. RTs were recorded during dual-task trials. Results showed that while young adults adopted an anticipatory control mode to move their COP as close as possible to the target center, seniors adopted a reactive control mode, lagging behind the target center. This resulted in longer COP-target distance and higher COP velocity in the latter group. Concurrently, RT increased more in seniors when switching from static stance to dynamic postural conditions, suggesting potential alterations in the central nervous system (CNS) functions. Finally, plantar flexor muscle fatigue and dual tasking had only minor effects on dynamic postural control of both young adults and seniors. Future studies should investigate why the fatigue-induced changes in quiet standing postural control do not seem to transfer to dynamic balance tasks. PMID- 26834625 TI - Age-Related Modifications of Diffusion Tensor Imaging Parameters and White Matter Hyperintensities as Inter-Dependent Processes. AB - Microstructural changes of White Matter (WM) associated with aging have been widely described through Diffusion Tensor Imaging (DTI) parameters. In parallel, White Matter Hyperintensities (WMH) as observed on a T2-weighted MRI are extremely common in older individuals. However, few studies have investigated both phenomena conjointly. The present study investigates aging effects on DTI parameters in absence and in presence of WMH. Diffusion maps were constructed based on 21 directions DTI scans of young adults (n = 19, mean age = 33 SD = 7.4) and two age-matched groups of older adults, one presenting low-level-WMH (n = 20, mean age = 78, SD = 3.2) and one presenting high-level-WMH (n = 20, mean age = 79, SD = 5.4). Older subjects with low-level-WMH presented modifications of DTI parameters in comparison to younger subjects, fitting with the DTI pattern classically described in aging, i.e., Fractional Anisotropy (FA) decrease/Radial Diffusivity (RD) increase. Furthermore, older subjects with high-level-WMH showed higher DTI modifications in Normal Appearing White Matter (NAWM) in comparison to those with low-level-WMH. Finally, in older subjects with high-level-WMH, FA, and RD values of NAWM were associated with to WMH burden. Therefore, our findings suggest that DTI modifications and the presence of WMH would be two inter dependent processes but occurring within different temporal windows. DTI changes would reflect the early phase of white matter changes and WMH would appear as a consequence of those changes. PMID- 26834627 TI - Expression of Alzheimer-Type Neurofibrillary Epitopes in Primary Rat Cortical Neurons Following Infection with Enterococcus faecalis. AB - The neurofibrillary tau pathology and amyloid deposits seen in Alzheimer's disease (AD) also have been seen in bacteria-infected brains. However, few studies have examined the role of these bacteria in the generation of tau pathology. One suggested link between infection and AD is edentulism, the complete loss of teeth. Edentulism can result from chronic periodontal disease due to infection by Enterococcus faecalis. The current study assessed the ability to generate early Alzheimer-like neurofibrillary epitopes in primary rat cortical neurons through bacterial infection by E. faecalis. Seven-day old cultured neurons were infected with E. faecalis for 24 and 48 h. An upward molecular weight shift in tau by Western blotting (WB) and increased appearance of tau reactivity in cell bodies and degenerating neurites was found in the 48 h infection group for the antibody CP13 (phospho-Serine 202). A substantial increase in reactivity of Alz-50 was seen at 24 and 48 h after infection. Furthermore, extensive microtubule-associated protein 2 (MAP2) reactivity also was seen at 24 and 48 h post-infection. Our preliminary findings suggest a potential link between E. faecalis infection and intracellular changes that may help facilitate early AD-like neurofibrillary pathology. HighlightsEnterococcus faecalis used in the generation of AD neurofibrillary epitopes in rat.Infection increases Alz-50, phospho-Serine 202 tau, and MAP2 expression.Infection by Enterococcus may play a role in early Alzheimer neurofibrillary changes. PMID- 26834628 TI - Electrophysiological Indicators of the Age-Related Deterioration in the Sensitivity to Auditory Duration Deviance. AB - The present study investigates age-related changes in duration discrimination in millisecond time domain. We tested young (N = 20, mean age = 24.5, SD = 2.97) and elderly (N = 20, mean age = 65.2, SD = 2.94) subjects using the mismatch negativity (MMN) paradigm. White-noise bursts of two different durations (50 and 10 ms) were presented in two oddball blocks. In one block (Increment Condition), the repetitive sequence of 10 ms standards was interspersed by occasional 50 ms deviants. In the Decrement Condition, the roles of the two stimuli were reversed. We analyzed the P1-N1 complex, MMN and P3a and found the effect of age for all these components. Moreover, the impact of stimulus presentation condition (increment/decrement) was observed for MMN and P3a. Our results confirmed the previous evidence for deteriorated duration discrimination in elderly people. Additionally, we found that this effect may be influenced by procedural factors. PMID- 26834630 TI - Commentary: Evidence for human transmission of amyloid-beta pathology and cerebral amyloid angiopathy. PMID- 26834631 TI - Editorial: ICT for Assessment and Rehabilitation in Alzheimer's Disease and Related Disorders. PMID- 26834629 TI - Abnormal Subcortical Brain Morphology in Patients with Knee Osteoarthritis: A Cross-sectional Study. AB - Despite the involvement of subcortical brain structures in the pathogenesis of chronic pain and persistent pain as the defining symptom of knee osteoarthritis (KOA), little attention has been paid to the morphometric measurements of these subcortical nuclei in patients with KOA. The purpose of this study is to explore the potential morphological abnormalities of subcortical brain structures in patients with KOA as compared to the healthy control subjects by using high resolution MRI. Structural MR data were acquired from 26 patients with KOA and 31 demographically similar healthy individuals. The MR data were analyzed by using FMRIB's integrated registration and segmentation tool. Both volumetric analysis and surface-based shape analysis were performed to characterize the subcortical morphology. The normalized volumes of bilateral caudate nucleus were significantly smaller in the KOA group than in the control group (P = 0.004). There was also a trend toward smaller volume of the hippocampus in KOA as compared to the control group (P = 0.027). Detailed surface analyses further localized these differences with a greater involvement of the left hemisphere (P < 0.05, corrected) for the caudate nucleus. Hemispheric asymmetry (right larger than left) of the caudate nucleus was found in both KOA and control groups. Besides, no significant correlation was found between the structural data and pain intensities. Our results indicated that patients with KOA had statistically significant smaller normalized volumes of bilateral caudate nucleus and a trend toward smaller volume of the hippocampus as compared to the control subjects. Further investigations are necessary to characterize the role of caudate nucleus in the course of chronicity of pain associated with KOA. PMID- 26834632 TI - Therapeutic Value of Voltage-Gated Sodium Channel Inhibitors in Breast, Colorectal, and Prostate Cancer: A Systematic Review. AB - Although survival rates of breast, colon, and prostate cancers are improving, deaths from these tumors frequently occur due to metastasis. Voltage-gated Na(+) channels (VGSCs) are membrane proteins, which regulate membrane current and cellular migration during nervous system organogenesis. VGSCs are also expressed in fibroblasts, immune cells, glia, and metastatic cancer cells. VGSCs regulate migration and invasion of breast, bowel, and prostate cancer cells, suggesting that they may be novel anti-metastatic targets. We conducted a systematic review of clinical and preclinical studies testing the effects of VGSC-inhibiting drugs in cancer. Two-hundred and four publications were identified, of which two human, two mouse, and 20 in vitro publications were included. In the clinical studies, the effect of these drugs on survival and metastatic relapse is not clear. The 22 preclinical studies collectively suggest that several VGSC-inhibiting drugs inhibit cancer proliferation, migration, and invasion. None of the human and only six of the preclinical studies directly investigated the effect of the drugs on VGSC activity. Studies were difficult to compare due to lack of standardized methodology and outcome measures. We conclude that the benefits of VGSC inhibitors require further investigation. Standardization of future studies and outcome measures should enable meaningful study comparisons. PMID- 26834633 TI - New Insight into the Anti-liver Fibrosis Effect of Multitargeted Tyrosine Kinase Inhibitors: From Molecular Target to Clinical Trials. AB - Tyrosine kinases (TKs) is a family of tyrosine protein kinases with important functions in the regulation of a broad variety of physiological cell processes. Overactivity of TK disturbs cellular homeostasis and has been linked to the development of certain diseases, including various fibrotic diseases. In regard to liver fibrosis, several TKs, such as vascular endothelial growth factor receptor, platelet-derived growth factor receptor, fibroblast growth factor receptor, and epidermal growth factor receptor kinases, have been identified as central mediators in collagen production and potential targets for anti-liver fibrosis therapies. Given the essential role of TKs during liver fibrogenesis, multitargeted inhibitors of aberrant TK activity, including sorafenib, erlotinib, imatinib, sunitinib, nilotinib, brivanib and vatalanib, have been shown to have potential for treating liver fibrosis. Beneficial effects are observed by researchers of this field using these multitargeted TK inhibitors in preclinical animal models and in patients with liver fibrosis. The present review will briefly summarize the anti-liver fibrosis effects of multitargeted TK inhibitors and molecular mechanisms. PMID- 26834634 TI - Silibinin Regulates Lipid Metabolism and Differentiation in Functional Human Adipocytes. AB - Silibinin, a natural plant flavonolignan is the main active constituent found in milk thistle (Silybum marianum). It is known to have hepatoprotective, anti neoplastic effect, and suppresses lipid accumulation in adipocytes. Objective of this study was to investigate the effect of silibinin on adipogenic differentiation and thermogenic capacity of human adipose tissue derived mesenchymal stem cells. Silibinin (10 MUM) treatment, either at the beginning or at the end of adipogenic differentiation, resulted in an increase of SIRT-1, PPARalpha, Pgc-1alpha, and UCPs gene expression. Moreover, silibinin administration resulted in a decrease of PPARgamma, FABP4, FAS, and MEST/PEG1 gene expression during the differentiation, confirming that this compound is able to reduce fatty acid accumulation and adipocyte size. Our data showed that silibinin regulated adipocyte lipid metabolism, inducing thermogenesis and promoting a brown remodeling in adipocyte. Taken together, our findings suggest that silibinin increases UCPs expression by stimulation of SIRT1, PPARalpha, and Pgc-1alpha, improved metabolic parameters, decreased lipid mass leading to the formation of functional adipocytes. PMID- 26834635 TI - Editorial: The Cell Types of Fibrosis. PMID- 26834638 TI - The Extract of Roots of Sophora flavescens Enhances the Recovery of Motor Function by Axonal Growth in Mice with a Spinal Cord Injury. AB - Although axonal extension to reconstruct spinal tracts should be effective for restoring function after spinal cord injury (SCI), chondroitin sulfate proteoglycan (CSPG) levels increase at spinal cord lesion sites, and inhibit axonal regrowth. In this study, we found that the water extract of roots of Sophora flavescens extended the axons of mouse cortical neurons, even on a CSPG coated surface. Consecutive oral administrations of S. flavescens extract to SCI mice for 31 days increased the density of 5-HT-positive axons at the lesion site and improved the motor function. Further, the active constituents in the S. flavescens extract were identified. The water and alkaloid fractions of the S. flavescens extract each exhibited axonal extension activity in vitro. LC/MS analysis revealed that these fractions mainly contain matrine and/or oxymatrine, which are well-known major compounds in S. flavescens. Matrine and oxymatrine promoted axonal extension on the CSPG-coated surface. This study is the first to demonstrate that S. flavescens extract, matrine, and oxymatrine enhance axonal growth in vitro, even on a CSPG-coated surface, and that S. flavescens extract improves motor function and increases axonal density in SCI mice. PMID- 26834639 TI - Protective Effects of HDL Against Ischemia/Reperfusion Injury. AB - Several lines of evidence suggest that, besides being a strong independent predictor of the occurrence of primary coronary events, a low plasma high density lipoprotein (HDL) cholesterol level is also associated with short- and long-term unfavorable prognosis in patients, who have recovered from a myocardial infarction, suggesting a direct detrimental effect of low HDL on post-ischemic myocardial function. Experiments performed in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury have clearly shown that HDL are able to preserve cardiac function when given before ischemia or at reperfusion; the protective effects of HDL against I/R injury have been also confirmed in other tissues and organs, as brain and hind limb. HDL were shown to act on coronary endothelial cells, by limiting the increase of endothelium permeability and promoting vasodilation and neoangiogenesis, on white blood cells, by reducing their infiltration into the ischemic tissue and the release of pro-inflammatory and matrix-degrading molecules, and on cardiomyocytes, by preventing the activation of the apoptotic cascade. Synthetic HDL retains the cardioprotective activity of plasma-derived HDL and may become a useful adjunctive therapy to improve clinical outcomes in patients with acute coronary syndromes or undergoing coronary procedures. PMID- 26834640 TI - Benchmarking Procedures for High-Throughput Context Specific Reconstruction Algorithms. AB - Recent progress in high-throughput data acquisition has shifted the focus from data generation to processing and understanding of how to integrate collected information. Context specific reconstruction based on generic genome scale models like ReconX or HMR has the potential to become a diagnostic and treatment tool tailored to the analysis of specific individuals. The respective computational algorithms require a high level of predictive power, robustness and sensitivity. Although multiple context specific reconstruction algorithms were published in the last 10 years, only a fraction of them is suitable for model building based on human high-throughput data. Beside other reasons, this might be due to problems arising from the limitation to only one metabolic target function or arbitrary thresholding. This review describes and analyses common validation methods used for testing model building algorithms. Two major methods can be distinguished: consistency testing and comparison based testing. The first is concerned with robustness against noise, e.g., missing data due to the impossibility to distinguish between the signal and the background of non specific binding of probes in a microarray experiment, and whether distinct sets of input expressed genes corresponding to i.e., different tissues yield distinct models. The latter covers methods comparing sets of functionalities, comparison with existing networks or additional databases. We test those methods on several available algorithms and deduce properties of these algorithms that can be compared with future developments. The set of tests performed, can therefore serve as a benchmarking procedure for future algorithms. PMID- 26834641 TI - Preparation of Paralympic Athletes; Environmental Concerns and Heat Acclimation. PMID- 26834636 TI - Physiological and Pathophysiological Insights of Nav1.4 and Nav1.5 Comparison. AB - Mutations in Nav1.4 and Nav1.5 alpha-subunits have been associated with muscular and cardiac channelopathies, respectively. Despite intense research on the structure and function of these channels, a lot of information is still missing to delineate the various physiological and pathophysiological processes underlying their activity at the molecular level. Nav1.4 and Nav1.5 sequences are similar, suggesting structural and functional homologies between the two orthologous channels. This also suggests that any characteristics described for one channel subunit may shed light on the properties of the counterpart channel subunit. In this review article, after a brief clinical description of the muscular and cardiac channelopathies related to Nav1.4 and Nav1.5 mutations, respectively, we compare the knowledge accumulated in different aspects of the expression and function of Nav1.4 and Nav1.5 alpha-subunits: the regulation of the two encoding genes (SCN4A and SCN5A), the associated/regulatory proteins and at last, the functional effect of the same missense mutations detected in Nav1.4 and Nav1.5. First, it appears that more is known on Nav1.5 expression and accessory proteins. Because of the high homologies of Nav1.5 binding sites and equivalent Nav1.4 sites, Nav1.5-related results may guide future investigations on Nav1.4. Second, the analysis of the same missense mutations in Nav1.4 and Nav1.5 revealed intriguing similarities regarding their effects on membrane excitability and alteration in channel biophysics. We believe that such comparison may bring new cues to the physiopathology of cardiac and muscular diseases. PMID- 26834637 TI - Anti-hypertensive Herbs and their Mechanisms of Action: Part I. AB - The use of herbal therapies for treatment and management of cardiovascular diseases (CVDs) is increasing. Plants contain a bounty of phytochemicals that have proven to be protective by reducing the risk of various ailments and diseases. Indeed, accumulating literature provides the scientific evidence and hence reason d'etre for the application of herbal therapy in relation to CVDs. Slowly, but absolutely, herbal remedies are being entrenched into evidence-based medical practice. This is partly due to the supporting clinical trials and epidemiological studies. The rationale for this expanding interest and use of plant based treatments being that a significant proportion of hypertensive patients do not respond to Modern therapeutic medication. Other elements to this equation are the cost of medication, side-effects, accessibility, and availability of drugs. Therefore, we believe it is pertinent to review the literature on the beneficial effects of herbs and their isolated compounds as medication for treatment of hypertension, a prevalent risk factor for CVDs. Our search utilized the PubMed and ScienceDirect databases, and the criterion for inclusion was based on the following keywords and phrases: hypertension, high blood pressure, herbal medicine, complementary and alternative medicine (CAM), nitric oxide, vascular smooth muscle cell (VSMC) proliferation, hydrogen sulfide, nuclear factor kappa-B, oxidative stress, and epigenetics/epigenomics. Each of the aforementioned keywords was co-joined with herb in question, and where possible with its constituent molecule(s). In this first of a two-part review, we provide a brief introduction of hypertension, followed by a discussion of the molecular and cellular mechanisms. We then present and discuss the plants that are most commonly used in the treatment and management of hypertension. PMID- 26834642 TI - Perspective: Does Laboratory-Based Maximal Incremental Exercise Testing Elicit Maximum Physiological Responses in Highly-Trained Athletes with Cervical Spinal Cord Injury? AB - The physiological assessment of highly-trained athletes is a cornerstone of many scientific support programs. In the present article, we provide original data followed by our perspective on the topic of laboratory-based incremental exercise testing in elite athletes with cervical spinal cord injury. We retrospectively reviewed our data on Great Britain Wheelchair Rugby athletes collected during the last two Paralympic cycles. We extracted and compared peak cardiometabolic (heart rate and blood lactate) responses between a standard laboratory-based incremental exercise test on a treadmill and two different maximal field tests (4 min and 40 min maximal push). In the nine athletes studied, both field tests elicited higher peak responses than the laboratory-based test. The present data imply that laboratory-based incremental protocols preclude the attainment of true peak cardiometabolic responses. This may be due to the different locomotor patterns required to sustain wheelchair propulsion during treadmill exercise or that maximal incremental treadmill protocols only require individuals to exercise at or near maximal exhaustion for a relatively short period of time. We acknowledge that both field- and laboratory-based testing have respective merits and pitfalls and suggest that the choice of test be dictated by the question at hand: if true peak responses are required then field-based testing is warranted, whereas laboratory-based testing may be more appropriate for obtaining cardiometabolic responses across a range of standardized exercise intensities. PMID- 26834643 TI - Positive Pacing Strategies Are Utilized by Elite Male and Female Para-cyclists in Short Time Trials in the Velodrome. AB - In para-cycling, competitors are classed based on functional impairment resulting in cyclists with neurological and locomotor impairments competing against each other. In Paralympic competition, classes are combined by using a factoring adjustment to race times to produce the overall medallists. Pacing in short duration track cycling events is proposed to utilize an "all-out" strategy in able-bodied competition. However, pacing in para-cycling may vary depending on the level of impairment. Analysis of the pacing strategies employed by different classification groups may offer scope for optimal performance; therefore, this study investigated the pacing strategy adopted during the 1-km time trial (TT) and 500-m TT in elite C1 to C3 para-cyclists and able-bodied cyclists. Total times and intermediate split times (125-m intervals; measured to 0.001 s) were obtained from the C1-C3 men's 1-km TT (n = 28) and women's 500-m TT (n = 9) from the 2012 Paralympic Games and the men's 1-km TT (n = 19) and women's 500-m TT (n = 12) from the 2013 UCI World Track Championships from publically available video. Split times were expressed as actual time, factored time (for the para cyclists) and as a percentage of total time. A two-way analysis of variance was used to investigate differences in split times between the different classifications and the able-bodied cyclists in the men's 1-km TT and between the para-cyclists and able-bodied cyclists in the women's 500-m TT. The importance of position at the first split was investigated with Kendall's Tau-b correlation. The first 125-m split time was the slowest for all cyclists, representing the acceleration phase from a standing start. C2 cyclists were slowest at this 125-m split, probably due to a combination of remaining seated in this acceleration phase and a high proportion of cyclists in this group being trans-femoral amputees. Not all cyclists used aero-bars, preferring to use drop, flat or bullhorn handlebars. Split times increased in the later stages of the race, demonstrating a positive pacing strategy. In the shorter women's 500-m TT, rank at the first split was more strongly correlated with final position than in the longer men's 1-km TT. In conclusion, a positive pacing strategy was adopted by the different para-cycling classes. PMID- 26834644 TI - Skeletal Muscle Mitochondrial Bioenergetics and Morphology in High Fat Diet Induced Obesity and Insulin Resistance: Focus on Dietary Fat Source. AB - It has been suggested that skeletal muscle mitochondria play a key role in high fat (HF) diet induced insulin resistance (IR). Two opposite views are debated on mechanisms by which mitochondrial function could be involved in skeletal muscle IR. In one theory, mitochondrial dysfunction is suggested to cause intramyocellular lipid accumulation leading to IR. In the second theory, excess fuel within mitochondria in the absence of increased energy demand stimulates mitochondrial oxidant production and emission, ultimately leading to the development of IR. Noteworthy, mitochondrial bioenergetics is strictly associated with the maintenance of normal mitochondrial morphology by maintaining the balance between the fusion and fission processes. A shift toward mitochondrial fission with reduction of fusion protein, mainly mitofusin 2, has been associated with reduced insulin sensitivity and inflammation in obesity and IR development. However, dietary fat source during chronic overfeeding differently affects mitochondrial morphology. Saturated fatty acids induce skeletal muscle IR and inflammation associated with fission phenotype, whereas omega-3 polyunsaturated fatty acids improve skeletal muscle insulin sensitivity and inflammation, associated with a shift toward mitochondrial fusion phenotype. The present minireview focuses on mitochondrial bioenergetics and morphology in skeletal muscle IR, with particular attention to the effect of different dietary fat sources on skeletal muscle mitochondria morphology and fusion/fission balance. PMID- 26834647 TI - Editorial: Redox Regulation in Skeletal Muscle Aging and Exercise. PMID- 26834646 TI - Editorial: Post-Exercise Recovery: Fundamental and Interventional Physiology. PMID- 26834645 TI - The Dynamic Nature of Hypertrophic and Fibrotic Remodeling of the Fish Ventricle. AB - Chronic pressure or volume overload can cause the vertebrate heart to remodel. The hearts of fish remodel in response to seasonal temperature change. Here we focus on the passive properties of the fish heart. Building upon our previous work on thermal-remodeling of the rainbow trout ventricle, we hypothesized that chronic cooling would initiate fibrotic cardiac remodeling, with increased myocardial stiffness, similar to that seen with pathological hypertrophy in mammals. We hypothesized that, in contrast to pathological hypertrophy in mammals, the remodeling response in fish would be plastic and the opposite response would occur following chronic warming. Rainbow trout held at 10 degrees C (control group) were chronically (>8 weeks) exposed to cooling (5 degrees C) or warming (18 degrees C). Chronic cold induced hypertrophy in the highly trabeculated inner layer of the fish heart, with a 41% increase in myocyte bundle cross-sectional area, and an up-regulation of hypertrophic marker genes. Cold acclimation also increased collagen deposition by 1.7-fold and caused an up regulation of collagen promoting genes. In contrast, chronic warming reduced myocyte bundle cross-sectional area, expression of hypertrophic markers and collagen deposition. Functionally, the cold-induced fibrosis and hypertrophy were associated with increased passive stiffness of the whole ventricle and with increased micromechanical stiffness of tissue sections. The opposite occurred with chronic warming. These findings suggest chronic cooling in the trout heart invokes a hypertrophic phenotype with increased cardiac stiffness and fibrosis that are associated with pathological hypertrophy in the mammalian heart. The loss of collagen and increased compliance following warming is particularly interesting as it suggests fibrosis may oscillate seasonally in the fish heart, revealing a more dynamic nature than the fibrosis associated with dysfunction in mammals. PMID- 26834650 TI - Timing Tasks Synchronize Cerebellar and Frontal Ramping Activity and Theta Oscillations: Implications for Cerebellar Stimulation in Diseases of Impaired Cognition. AB - Timing is a fundamental and highly conserved mammalian capability, yet the underlying neural mechanisms are widely debated. Ramping activity of single neurons that gradually increase or decrease activity to encode the passage of time has been speculated to predict a behaviorally relevant temporal event. Cue evoked low-frequency activity has also been implicated in temporal processing. Ramping activity and low-frequency oscillations occur throughout the brain and could indicate a network-based approach to timing. Temporal processing requires cognitive mechanisms of working memory, attention, and reasoning, which are dysfunctional in neuropsychiatric disease. Therefore, timing tasks could be used to probe cognition in animals with disease phenotypes. The medial frontal cortex and cerebellum are involved in cognition. Cerebellar stimulation has been shown to influence medial frontal activity and improve cognition in schizophrenia. However, the mechanism underlying the efficacy of cerebellar stimulation is unknown. Here, we discuss how timing tasks can be used to probe cerebellar interactions with the frontal cortex and the therapeutic potential of cerebellar stimulation. The goal of this theory and hypothesis manuscript is threefold. First, we will summarize evidence indicating that in addition to motor learning, timing tasks involve cognitive processes that are present within both the cerebellum and medial frontal cortex. Second, we propose methodologies to investigate the connections between these areas in patients with Parkinson's disease, autism, and schizophrenia. Lastly, we hypothesize that cerebellar transcranial stimulation may rescue medial frontal ramping activity, theta oscillations, and timing abnormalities, thereby restoring executive function in diseases of impaired cognition. This hypothesis could inspire the use of timing tasks as biomarkers for neuronal and cognitive abnormalities in neuropsychiatric disease and promote the therapeutic potential of the cerebellum in diseases of impaired cognition. PMID- 26834648 TI - Theory of Mind in Bipolar Disorder, with Comparison to the Impairments Observed in Schizophrenia. AB - Our ability to make sense of information on the potential intentions and dispositions of others is of paramount importance for understanding their communicative intent, and for judging what an appropriate reaction might be. Thus, anything that impinges on this ability has the potential to cause significant social impairment, and compromise an individual's level of functioning. Both bipolar disorder and schizophrenia are known to feature theory of mind impairment. We conducted a theoretical review to determine the extent and types of theory of mind impairment in bipolar disorder, and evaluate their relationship to medication and symptoms. We also considered possible mediatory mechanisms, and set out to discover what else could be learnt about the impairment in bipolar disorder by comparison to the profile of impairment in schizophrenia. The literature established that in bipolar disorder (i) some form of theory of mind impairment has been observed in all mood states, including euthymia, (ii) the form of theory of mind assessed and task used to make the assessment influence the impairment observed, and (iii) there might be some relationship to cognitive impairment, although a relationship to standard clinical variables was harder to establish. What also became clear in the literature on bipolar disorder itself was the possible relationship of theory of mind impairment to history of psychotic symptoms. Direct comparative studies, including patients with schizophrenia, were thus examined, and provided several important directions for future research on the bases of impairment in bipolar disorder. Particularly prominent was the issue of whether theory of mind impairment could be considered a candidate endophenotype for the psychoses, although current evidence suggests that this may be premature. The differences in impairment across schizophrenia and bipolar disorder may, however, have genuine differential effects on social functioning and the likely success of remediation. PMID- 26834651 TI - Oxytocin for Male Subjects with Autism Spectrum Disorder and Comorbid Intellectual Disabilities: A Randomized Pilot Study. AB - Approximately half of autism spectrum disorder (ASD) individuals suffer from comorbid intellectual disabilities (IDs). Oxytocin (OXT) receptors are highly expressed in temporal lobe structures and are likely to play a modulatory role in excitatory/inhibitory balance, at least based on animal model findings. Thus, it is feasible that in the highly representative group of Kanner-type ASD subjects, OXT could have a beneficial effect on social communication and social interaction. The aim of this pilot study is to investigate the feasibility and adverse events, such as epilepsy, of the long-term administration of intranasal OXT for adolescent and adult ASD subjects with ID because such patients frequently have seizures. We also addressed the question on how to scale the OXT effects to the core symptoms of social deficits because of the relative difficulty in obtaining objective measurements. Twenty-nine males (aged 15-40 years old) participated in a randomized, double-blind, and placebo-controlled crossover study (each for 8 weeks) with OXT (16 IU/day). Except for seizures experienced by one participant, other serious adverse events did not occur. The primary and secondary outcomes measured using the Childhood Autism Rating Scale and several standard scales, respectively, revealed no difference between the OXT and placebo groups. Instead, in an exploratory analysis, the social interactions observed in the play sessions or in daily life were significantly more frequent in the initial half period in the OXT-first arm of the crossover trial. There were also significant correlations between the plasma OXT concentration and subscale scores for irritability on the Aberrant Behavior Checklist. In conclusion, this pilot study demonstrates that long-term administration of intranasal OXT is tolerable in a representative cohort of ASD individuals with ID and suggests that future multicenter trials of OXT are warranted and should include measurements of reciprocal social interactions based on daily life under closer surveillance for epilepsy. TRIAL REGISTRATION: UMIN000007250. PMID- 26834652 TI - Insular Volume Reduction in Patients with Social Anxiety Disorder. AB - Despite the fact that social anxiety disorder (SAD) is highly prevalent, there have been only a few structural imaging studies. Moreover, most of them reported about a volume reduction in amygdale, which plays a key role in the neural function of SAD. Insula is another region of interest. Its hyperactivity in regard to processing negative emotional information or interoceptive awareness has been detected in patients with SAD. Referring to these studies, we hypothesized that insular volumes might reduce in patients with SAD and made a comparison of insular volumes between 13 patients with SAD and 18 healthy controls with matched age and gender using voxel-based morphometry. As a result, we found a significant volume reduction in insula in the SAD group. Our results suggest that the patients with SAD might have an insular volume reduction apart from amygdala. Since insula plays a critical role in the pathology of SAD, more attention should be paid not only to functional study but also morphometrical study of insula. PMID- 26834649 TI - Neuropsychological Consequences of Chronic Drug Use: Relevance to Treatment Approaches. AB - Heavy use of drugs impacts of the daily activities of individuals in these activities. Several groups of investigators have indeed documented changes in cognitive performance by individuals who have a long history of chronic drug use. In the case of marijuana, a wealth of information suggests that heavy long-term use of the drug may have neurobehavioral consequences in some individuals. In humans, heavy cocaine use is accompanied by neuropathological changes that might serve as substrates for cognitive dysfunctions. Similarly, methamphetamine users suffer from cognitive abnormalities that may be consequent to alterations in structures and functions. Here, we detail the evidence for these neuropsychological consequences. The review suggests that improving the care of our patients will necessarily depend on the better characterization of drug induced cognitive phenotypes because they might inform the development of better pharmacological and behavioral interventions, with the goal of improving cognitive functions in these subsets of drug users. PMID- 26834654 TI - Maintaining Life Satisfaction in Adolescence: Affective Mediators of the Influence of Perceived Emotional Intelligence on Overall Life Satisfaction Judgments in a Two-Year Longitudinal Study. AB - Much attention has been paid to the psychological processes underlying the improvement in mood states and human well-being, particularly during adolescence. Theoretical and empirical research suggests that emotional skills may play a role in enhancing perceived well-being; however, the mechanisms involved in during adolescence are unclear. The purpose of this study was to extend understanding by investigating the potential mediators of the relationship between emotional intelligence (EI) and life satisfaction in a 2-years study. Participants were 269 high school students (145 girls and 124 boys) who completed the self-report perceived emotional intelligence (PEI) Scale, the Satisfaction with Life Scale, and the Positive Affect and Negative Affect Scale three times at 1-year intervals. The three-step longitudinal design corroborated earlier research indicating that positive and negative affect mediate the relationships between EI and life satisfaction. Students with high PEI tended to have more positive experiences and fewer negative experiences, which contributed to their greater life satisfaction. No sex differences were found in the multi-group analyses, suggesting that the causal relationships are similar in both sexes. These findings extend our understanding of the complex network of relationships involving PEI and life satisfaction in adolescence. Implications and limitations of the findings are discussed. PMID- 26834655 TI - On the Use of Response Chunking as a Tool to Investigate Strategies. AB - In this perspective we suggest that chunking can be used as an investigative tool to determine the characteristics of other cognitive phenomena. We present an example of the usefulness of chunking multiple responses to aid in understanding object switch costs. Switch costs refer to the shorter response times for manipulation of the same item on two trials in a row compared to a switch between items. It is presently unclear if this result is due to structural or strategic processes. We provide a short review of past literature on switch costs and a proof-of-concept example that chunking may shed new light on this topic. We examined this question with boxes filled with numbers to be arithmetically updated and memorized. A situation in which there were two response items to be manipulated per trial eliminated or reversed the switch cost effect. We suggest that participants use a strategy in which the two output responses were chunked together, making it unfeasible to prepare separately for a repetition of the most recent item as participants do in other circumstances. Our data suggest that even a well-studied phenomenon can benefit theoretically from the use of chunking as a research tool. PMID- 26834653 TI - New Insights into the Nature of Cerebellar-Dependent Eyeblink Conditioning Deficits in Schizophrenia: A Hierarchical Linear Modeling Approach. AB - Evidence of cerebellar dysfunction in schizophrenia has mounted over the past several decades, emerging from neuroimaging, neuropathological, and behavioral studies. Consistent with these findings, cerebellar-dependent delay eyeblink conditioning (dEBC) deficits have been identified in schizophrenia. While repeated-measures analysis of variance is traditionally used to analyze dEBC data, hierarchical linear modeling (HLM) more reliably describes change over time by accounting for the dependence in repeated-measures data. This analysis approach is well suited to dEBC data analysis because it has less restrictive assumptions and allows unequal variances. The current study examined dEBC measured with electromyography in a single-cue tone paradigm in an age-matched sample of schizophrenia participants and healthy controls (N = 56 per group) using HLM. Subjects participated in 90 trials (10 blocks) of dEBC, during which a 400 ms tone co-terminated with a 50 ms air puff delivered to the left eye. Each block also contained 1 tone-alone trial. The resulting block averages of dEBC data were fitted to a three-parameter logistic model in HLM, revealing significant differences between schizophrenia and control groups on asymptote and inflection point, but not slope. These findings suggest that while the learning rate is not significantly different compared to controls, associative learning begins to level off later and a lower ultimate level of associative learning is achieved in schizophrenia. Given the large sample size in the present study, HLM may provide a more nuanced and definitive analysis of differences between schizophrenia and controls on dEBC. PMID- 26834657 TI - Stakeholders' Responses to CSR Tradeoffs: When Other-Orientation and Trust Trump Material Self-Interest. AB - When investing in corporate social responsibility (CSR), managers may strive for a win-win scenario where all stakeholders end up better off, but they may not always be able to avoid trading off stakeholders' interests. To provide guidance to managers who have to make tradeoffs, this study used a vignette-based experiment to explore stakeholders' intention to associate with a firm (i.e., buy from or become an employee) that trades off CSR directed at the stakeholders' own group (self-directed CSR) and CSR directed at another stakeholder group (other directed CSR). Results show that stakeholders were not systematically more attracted to a firm that favors their own group over another stakeholder group. Specifically, stakeholders' other-orientation moderated their reaction to tradeoffs: stakeholders higher on other-orientation were willing to forego some material benefits to associate with a firm that treated suppliers in developing countries significantly better than its competitors, whereas stakeholders lower on other-orientation were more attracted to a firm favoring their own stakeholder group. Other-orientation also moderated reactions to tradeoffs involving the environment, although high CSR directed at the environment did not compensate for low self-directed CSR even for stakeholders higher on other-orientation. Second, the vignette study showed that trust mediated the relationship between tradeoffs and stakeholders' reactions. The study contributes first and foremost to the burgeoning literature on CSR tradeoffs and to the multimotive approach to CSR, which claims that other motives can drive stakeholders' reactions to CSR in addition to self-interest. First, it provides further evidence that studying CSR tradeoffs is important to understand both (prospective) employees' and customers' reactions to CSR-related activities. Second, it identifies other-orientation as a motive-related individual difference that explains heterogeneity in stakeholders' reactions to CSR. These findings suggest several avenues for future research for organizational psychologists interested in organizational justice. Third, it investigates trust as a mediating mechanism. Fourth, it reveals differences in stakeholders' reactions depending on which other stakeholder group is involved in the tradeoff. For practice, the findings suggest that tradeoffs are important because they influence which stakeholders are attracted to the firm. PMID- 26834656 TI - Chemosensory Communication of Gender Information: Masculinity Bias in Body Odor Perception and Femininity Bias Introduced by Chemosignals During Social Perception. AB - Human body odor is a source of important social information. In this study, we explore whether the sex of an individual can be established based on smelling axillary odor and whether exposure to male and female odors biases chemosensory and social perception. In a double-blind, pseudo-randomized application, 31 healthy normosmic heterosexual male and female raters were exposed to male and female chemosignals (odor samples of 27 heterosexual donors collected during a cardio workout) and a no odor sample. Recipients rated chemosensory samples on a masculinity-femininity scale and provided intensity, familiarity and pleasantness ratings. Additionally, the modulation of social perception (gender-neutral faces and personality attributes) and affective introspection (mood) by male and female chemosignals was assessed. Male and female axillary odors were rated as rather masculine, regardless of the sex of the donor. As opposed to the masculinity bias in the odor perception, a femininity bias modulating social perception appeared. A facilitated femininity detection in gender-neutral faces and personality attributes in male and female chemosignals appeared. No chemosensory effect on mood of the rater was observed. The results are discussed with regards to the use of male and female chemosignals in affective and social communication. PMID- 26834658 TI - Prediction of Treatment Outcome in Patients with Obsessive-Compulsive Disorder with Low-Resolution Brain Electromagnetic Tomography: A Prospective EEG Study. AB - The issue of predicting treatment response and identifying, in advance, which patient will profit from treating obsessive-compulsive disorder (OCD) seems to be an elusive goal. This prospective study investigated brain electric activity [using Low-Resolution Brain Electromagnetic Tomography (LORETA)] for the purpose of predicting response to treatment. Forty-one unmedicated patients with a DSM-IV diagnosis of OCD were included. A resting 32-channel EEG was obtained from each participant before and after 10 weeks of standardized treatment with sertraline and behavioral therapy. LORETA was used to localize the sources of brain electrical activity. At week 10, patients were divided into responders and non responders (according to a reduction of symptom severity >50% on the Y-BOCS). LORETA analysis revealed that at baseline responders showed compared to non responders a significantly lower brain electric activity within the beta 1 (t = 2.86, p < 0.05), 2 (t = 2.81, p < 0.05), and 3 (t = 2.76, p < 0.05) frequency bands and ROI analysis confirmed a reduced activity in alpha 2 (t = 2.06, p < 0.05) in the anterior cingulate cortex (ACC). When baseline LORETA data were compared to follow-up data, the analysis showed in the responder group a significantly lower brain electrical resting activity in the beta 1 (t = 3.17. p < 0.05) and beta 3 (t = 3.11. p < 0.05) frequency bands and equally for the ROI analysis of the orbitofrontal cortex (OFC) in the alpha 2 (t = 2.15. p < 0.05) frequency band. In the group of non-responders the opposite results were found. In addition, a positive correlation between frequency alpha 2 (rho = 0.40, p = 0.010), beta 3 (rho = 0.42, p = 0.006), delta (rho = 0.33, p = 0.038), theta (rho = 0.34, p = 0.031), alpha 1 (rho = 0.38, p = 0.015), and beta1 (rho = 0.34, p = 0.028) of the OFC and the bands delta (rho = 0.33, p = 0.035), alpha 1 (rho = 0.36, p = 0.019), alpha 2 (rho = 0.34, p = 0.031), and beta 3 (rho = 0.38, p = 0.015) of the ACC with a reduction of the Y-BOCS scores was identified. Our results suggest that measuring brain activity with LORETA could be an efficient and applicable technique to prospectively identify treatment responders in OCD. PMID- 26834659 TI - Asymmetric Switch Costs in Numeral Naming and Number Word Reading: Implications for Models of Bilingual Language Production. AB - One approach used to gain insight into the processes underlying bilingual language comprehension and production examines the costs that arise from switching languages. For unbalanced bilinguals, asymmetric switch costs are reported in speech production, where the switch cost for L1 is larger than the switch cost for L2, whereas, symmetric switch costs are reported in language comprehension tasks, where the cost of switching is the same for L1 and L2. Presently, it is unclear why asymmetric switch costs are observed in speech production, but not in language comprehension. Three experiments are reported that simultaneously examine methodological explanations of task related differences in the switch cost asymmetry and the predictions of three accounts of the switch cost asymmetry in speech production. The results of these experiments suggest that (1) the type of language task (comprehension vs. production) determines whether an asymmetric switch cost is observed and (2) at least some of the switch cost asymmetry arises within the language system. PMID- 26834660 TI - Foundations of Intervention Research in Instrumental Practice. AB - The goals of the present study are to evaluate, implement, and adapt psychological skills used in the realm of sports into music performance. This research project also aims to build foundations on how to implement future interventions to guide music students on how to optimize practice toward performance. A 2-month psychological skills intervention was provided to two students from the national music academy's bachelor program in music performance to better understand how to adapt and construct psychological skills training programs for performing music students. The program evaluated multiple intervention tools including the use of questionnaires, performance profiling, iPads, electronic practice logs, recording the perceived value of individual and combined work, as well as the effectiveness of different communication forms. Perceived effects of the intervention were collected through semi-structured interviews, observations, and logs. PMID- 26834661 TI - Highly Superior Autobiographical Memory: Quality and Quantity of Retention Over Time. AB - Individuals who have Highly Superior Autobiographical Memory (HSAM) are able to recall, with considerable accuracy, details of daily experiences that occurred over many previous decades. The present study parametrically investigates the quantity and quality of details of autobiographical memories acquired 1-week, 1 month, 1-year, and 10-years prior in HSAMs and controls. In addition, we tested the consistency of details provided at the 1-week delay by testing the subjects 1 month later with a surprise assessment. At the 1-week delay, HSAMs and controls recalled an equivalent number of events. In contrast, HSAM recall performance was superior at more remote delays, with remarkable consistency following a 1-month delay. Further, we revealed a relationship between the consistency of recall and HSAMs' obsessive-compulsive tendencies. These data suggest that HSAMs experience normal encoding, yet enhanced consolidation and later recall of autobiographical events. PMID- 26834662 TI - Does Gender-Fair Language Pay Off? The Social Perception of Professions from a Cross-Linguistic Perspective. AB - In many languages, masculine forms (e.g., German Lehrer, "teachers, masc.") have traditionally been used to refer to both women and men, although feminine forms are available, too. Feminine-masculine word pairs (e.g., German Lehrerinnen und Lehrer, "teachers, fem. and teachers, masc.") are recommended as gender-fair alternatives. A large body of empirical research documents that the use of gender fair forms instead of masculine forms has a substantial impact on mental representations. Masculine forms activate more male representations even when used in a generic sense, whereas word pairs (e.g., German Lehrerinnen und Lehrer, "teachers, fem. and teachers, masc.") lead to a higher cognitive inclusion of women (i.e., visibility of women). Some recent studies, however, have also shown that in a professional context word pairs may be associated with lesser status. The present research is the first to investigate both effects within a single paradigm. A cross-linguistic (Italian and German) study with 391 participants shows that word pairs help to avoid a male bias in the gender-typing of professions and increase women's visibility; at the same time, they decrease the estimated salaries of typically feminine professions (but do not affect perceived social status or competence). This potential payoff has implications for language policies aiming at gender-fairness. PMID- 26834663 TI - A Concise History of Asperger Syndrome: The Short Reign of a Troublesome Diagnosis. AB - First described in 1944 by Hans Asperger (1944), it was not before 1994 that Asperger Syndrome (AS) was included in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders, only to disappear in the Manual's fifth edition in 2013. During its brief existence as a diagnostic entity, AS aroused immense interest and controversy. Similar to patients with autism, AS patients show deficits in social interaction, inappropriate communication skills, and interest restriction, but also display a rich variety of subtle clinical characteristics that for many distinguish AS from autism. However, difficulties operationalising diagnostic criteria and differentiating AS from autism ultimately led to its merging into the unifying category of Autistic Spectrum Disorders. Here we briefly review the short history of this fascinating condition. PMID- 26834664 TI - Revisiting the Master-Signifier, or, Mandela and Repression. AB - The concept of the master-signifier has been subject to a variety of applications in Lacanian forms of political discourse theory and ideology critique. While there is much to be commended in literature of this sort, it often neglects salient issues pertaining to the role of master signifiers in the clinical domain of (individual) psychical economy. The popularity of the concept of the master (or "empty") signifier in political discourse analysis has thus proved a double edged sword. On the one hand it demonstrates how crucial psychical processes are performed via the operations of the signifier, extending thus the Lacanian thesis that identification is the outcome of linguistic and symbolic as opposed to merely psychological processes. On the other, the use of the master signifier concept within the political realm to track discursive formations tends to distance the term from the dynamics of the unconscious and operation of repression. Accordingly, this paper revisits the master signifier concept, and does so within the socio-political domain, yet while paying particular attention to the functioning of unconscious processes of fantasy and repression. More specifically, it investigates how Nelson Mandela operates as a master signifier in contemporary South Africa, as a vital means of knitting together diverse elements of post-apartheid society, enabling the fantasy of the post-apartheid nation, and holding at bay a whole series of repressed and negated undercurrents. PMID- 26834665 TI - Children's Recall of Words Spoken in Their First and Second Language: Effects of Signal-to-Noise Ratio and Reverberation Time. AB - Speech perception runs smoothly and automatically when there is silence in the background, but when the speech signal is degraded by background noise or by reverberation, effortful cognitive processing is needed to compensate for the signal distortion. Previous research has typically investigated the effects of signal-to-noise ratio (SNR) and reverberation time in isolation, whilst few have looked at their interaction. In this study, we probed how reverberation time and SNR influence recall of words presented in participants' first- (L1) and second language (L2). A total of 72 children (10 years old) participated in this study. The to-be-recalled wordlists were played back with two different reverberation times (0.3 and 1.2 s) crossed with two different SNRs (+3 dBA and +12 dBA). Children recalled fewer words when the spoken words were presented in L2 in comparison with recall of spoken words presented in L1. Words that were presented with a high SNR (+12 dBA) improved recall compared to a low SNR (+3 dBA). Reverberation time interacted with SNR to the effect that at +12 dB the shorter reverberation time improved recall, but at +3 dB it impaired recall. The effects of the physical sound variables (SNR and reverberation time) did not interact with language. PMID- 26834666 TI - Age-Related Differences and Cognitive Correlates of Self-Reported and Direct Navigation Performance: The Effect of Real and Virtual Test Conditions Manipulation. AB - The present study investigated the effect of aging on direct navigation measures and self-reported ones according to the real-virtual test manipulation. Navigation (wayfinding tasks) and spatial memory (paper-pencil tasks) performances, obtained either in real-world or in virtual-laboratory test conditions, were compared between young (n = 32) and older (n = 32) adults who had self-rated their everyday navigation behavior (SBSOD scale). Real age-related differences were observed in navigation tasks as well as in paper-pencil tasks, which investigated spatial learning relative to the distinction between survey route knowledge. The manipulation of test conditions (real vs. virtual) did not change these age-related differences, which are mostly explained by age-related decline in both spatial abilities and executive functioning (measured with neuropsychological tests). In contrast, elderly adults did not differ from young adults in their self-reporting relative to everyday navigation, suggesting some underestimation of navigation difficulties by elderly adults. Also, spatial abilities in young participants had a mediating effect on the relations between actual and self-reported navigation performance, but not for older participants. So, it is assumed that the older adults carried out the navigation task with fewer available spatial abilities compared to young adults, resulting in inaccurate self-estimates. PMID- 26834667 TI - Talker-Specific Generalization of Pragmatic Inferences based on Under- and Over Informative Prenominal Adjective Use. AB - According to Grice's (1975) Maxim of Quantity, rational talkers formulate their utterances to be as economical as possible while conveying all necessary information. Naturally produced referential expressions, however, often contain more or less information than what is predicted to be optimal given a rational speaker model. How do listeners cope with these variations in the linguistic input? We argue that listeners navigate the variability in referential resolution by calibrating their expectations for the amount of linguistic signal to be expended for a certain meaning and by doing so in a context- or a talker-specific manner. Focusing on talker-specificity, we present four experiments. We first establish that speakers will generalize information from a single pair of adjectives to unseen adjectives in a speaker-specific manner (Experiment 1). Initially focusing on exposure to underspecified utterances, Experiment 2 examines: (a) the dimension of generalization; (b) effects of the strength of the evidence (implicit or explicit); and (c) individual differences in dimensions of generalization. Experiments 3 and 4 ask parallel questions for exposure to over specified utterances, where we predict more conservative generalization because, in spontaneous utterances, talkers are more likely to over-modify than under modify. PMID- 26834668 TI - Humans Integrate Monetary and Liquid Incentives to Motivate Cognitive Task Performance. AB - It is unequivocal that a wide variety of incentives can motivate behavior. However, few studies have explicitly examined whether and how different incentives are integrated in terms of their motivational influence. The current study examines the combined effects of monetary and liquid incentives on cognitive processing, and whether appetitive and aversive incentives have distinct influences. We introduce a novel task paradigm, in which participants perform cued task-switching for monetary rewards that vary parametrically across trials, with liquid incentives serving as post-trial performance feedback. Critically, the symbolic meaning of the liquid was held constant (indicating successful reward attainment), while liquid valence was blocked. In the first experiment, monetary rewards combined additively with appetitive liquid feedback to improve subject task performance. Aversive liquid feedback counteracted monetary reward effects in low monetary reward trials, particularly in a subset of participants who tended to avoid responding under these conditions. Self report motivation ratings predicted behavioral performance above and beyond experimental effects. A follow-up experiment replicated the predictive power of motivation ratings even when only appetitive liquids were used, suggesting that ratings reflect idiosyncratic subjective values of, rather than categorical differences between, the liquid incentives. Together, the findings indicate an integrative relationship between primary and secondary incentives and potentially dissociable influences in modulating motivational value, while informing hypotheses regarding candidate neural mechanisms. PMID- 26834670 TI - Being Present in Action: A Theoretical Model About the "Interlocking" Between Intentions and Environmental Affordances. AB - Recent neuropsychological evidence suggest that a key role in linking perceptions and intentions is played by sense of presence. Despite this phenomenon having been studied primarily in the field of virtual reality (conceived as the illusion of being in the virtual space), recent research highlighted that it is a fundamental feature of everyday experience. Specifically, the function of presence as a cognitive process is to locate the Self in a physical space or situation, based on the perceived possibility to act in it; so, the variations in sense of presence allow one to continuously adapt his own action to the external environment. Indeed intentions, as the cognitive antecedents of action, are not static representations of the desired outcomes, but dynamic processes able to adjust their own representational content according to the opportunities/restrictions emerging in the environment. Focusing on the peculiar context of action mediated by interactive technologies, we here propose a theoretical model showing how each level of an intentional hierarchy (future directed; present directed; and motor intentions) can "interlock" with environmental affordances in order to promote a continuous stream of action and activity. PMID- 26834669 TI - Does Mindfulness Enhance Critical Thinking? Evidence for the Mediating Effects of Executive Functioning in the Relationship between Mindfulness and Critical Thinking. AB - Mindfulness originated in the Buddhist tradition as a way of cultivating clarity of thought. Despite the fact that this behavior is best captured using critical thinking (CT) assessments, no studies have examined the effects of mindfulness on CT or the mechanisms underlying any such possible relationship. Even so, mindfulness has been suggested as being beneficial for CT in higher education. CT is recognized as an important higher-order cognitive process which involves the ability to analyze and evaluate evidence and arguments. Such non-automatic, reflective responses generally require the engagement of executive functioning (EF) which includes updating, inhibition, and shifting of representations in working memory. Based on research showing that mindfulness enhances aspects of EF and certain higher-order cognitive processes, we hypothesized that individuals higher in facets of dispositional mindfulness would demonstrate greater CT performance, and that this relationship would be mediated by EF. Cross-sectional assessment of these constructs in a sample of 178 university students was achieved using the observing and non-reactivity sub-scales of the Five Factor Mindfulness Questionnaire, a battery of EF tasks and the Halpern Critical Thinking Assessment. Our hypotheses were tested by constructing a multiple meditation model which was analyzed using Structural Equation Modeling. Evidence was found for inhibition mediating the relationships between both observing and non-reactivity and CT in different ways. Indirect-only (or full) mediation was demonstrated for the relationship between observing, inhibition, and CT. Competitive mediation was demonstrated for the relationship between non reactivity, inhibition, and CT. This suggests additional mediators of the relationship between non-reactivity and CT which are not accounted for in this model and have a negative effect on CT in addition to the positive effect mediated by inhibition. These findings are discussed in the context of the Default Interventionist Dual Process Theory of Higher-order Cognition and previous studies on mindfulness, self-regulation, EF, and higher-order cognition. In summary, dispositional mindfulness appears to facilitate CT performance and this effect is mediated by the inhibition component of EF. However, this relationship is not straightforward which suggests many possibilities for future research. PMID- 26834671 TI - Pragmatics as Metacognitive Control. AB - The term "pragmatics" is often used to refer without distinction, on one hand, to the contextual selection of interpretation norms and, on the other hand, to the context-sensitive processes guided by these norms. Pragmatics in the first acception depends on language-independent contextual factors that can, but need not, involve Theory of Mind; in the second acception, pragmatics is a language specific metacognitive process, which may unfold at an unconscious level without involving any mental state (meta-)representation. Distinguishing between these two kinds of ways context drives the interpretation of communicative stimuli helps dissolve the dispute between proponents of an entirely Gricean pragmatics and those who claim that some pragmatic processes do not depend on mind-reading capacities. According to the model defended in this paper, the typology of pragmatic processes is not entirely determined by a hierarchy of meanings, but by contextually set norms of interpretation. PMID- 26834672 TI - Reading Emotions from Body Movement: A Generalized Impairment in Schizophrenia. AB - Body language reading is a social cognitive process with importance for successful maneuvering of social situations. In this study, we investigated body language reading as assessed with human point-light displays in participants with a diagnosis of schizophrenia (n = 84) compared to healthy control participants (n = 84), aiming to answer three questions: (1) whether persons with a diagnosis of schizophrenia have poorer body language reading abilities than healthy persons; (2) whether some emotions are easier to read from body language than others, and if this is the same for individuals with schizophrenia and healthy individuals, and (3) whether there are sex differences in body language reading in participants with schizophrenia and healthy participants. A fourth research aim concerned associations of body language reading with symptoms and functioning in participants with schizophrenia. Scores on the body language reading measure was first standardized using a separate sample of healthy control participants (n = 101). Further results showed that persons with schizophrenia had impaired body language reading ability compared to healthy persons. A significant effect of emotion indicated that some emotions (happiness, neutral) were easier to recognize and this was so for both individuals with schizophrenia and healthy individuals. There were no sex differences for either diagnostic group. Body language reading ability was not associated with symptoms or functioning. In conclusion; schizophrenia was characterized by a global impairment in body language reading that was present for all emotions and across sex. PMID- 26834673 TI - Recognition Memory is Improved by a Structured Temporal Framework During Encoding. AB - In order to function optimally within our environment, we continuously extract temporal patterns from our experiences and formulate expectations that facilitate adaptive behavior. Given that our memories are embedded within spatiotemporal contexts, an intriguing possibility is that mnemonic processes are sensitive to the temporal structure of events. To test this hypothesis, in a series of behavioral experiments we manipulated the regularity of interval durations at encoding to create temporally structured and unstructured frameworks. Our findings revealed enhanced recognition memory (d') for stimuli that were explicitly encoded within a temporally structured vs. unstructured framework. Encoding information within a temporally structured framework was also associated with a reduction in the negative effects of proactive interference and was linked to greater recollective recognition memory. Furthermore, rhythmic temporal structure was found to enhance recognition memory for incidentally encoded information. Collectively, these results support the possibility that we possess a greater capacity to learn and subsequently remember temporally structured information. PMID- 26834674 TI - Not Just Being Lifted: Infants are Sensitive to Delay During a Pick-Up Routine. AB - In the present study we observed whether infants show online adjustments to the mother's incipient action by looking at their sensitivity to changes as the pick up unfolded. Twenty-three 3-month-old infants and their mothers were observed in the lab, where mothers were instructed (1) to pick-up their infants as they usually did (normal pick-up), and then (2) to delay the pick-up for 6 s after placing their hands on the infants' waist (delayed pick-up). In both Normal and Delayed conditions infant's body tension, affective displays and gaze shifts were coded during three phases: Approach, Contact, and Lift. Additionally, a measure of infants' head support in terms of head lag at the beginning and end of Lift was computed. Results showed that during normal pick-up infants tensed up their body during the Approach phase and increased their tension during contact, maintaining it through Lift; their head was also supported and in line with their body during Lift. When the pick-up was delayed, infants also tensed their body during Approach, yet this tension did not increase during the Contact phase and was significantly lower at Lift. Their head support was also lower in the Delayed condition and they shifted their gazes away from their mothers' face more often than in the Normal condition. These results suggest that infants are sensitive to changes of the timing of the pick-up sequence, which in turn may have affected their contribution to the interaction. PMID- 26834675 TI - Songs for the Ego: Theorizing Musical Self-Enhancement. AB - This paper outlines a theoretical account of musical self-enhancement. I claim that listening to music serves as a resource for actively manipulating affective states so that a positive self-view is maintained and a sense of optimism is provided. Self-enhancement-the process by which individuals modify their self worth and gain self-esteem-typically takes place in social interactions. I argue that experiencing music may serve as a unique "esthetic surrogate" for interaction, which equally enables self-enhancement. This ability relies on three main characteristics of the musical experience, namely, its capacity to (a) evoke empathetic feelings, (b) elicit social cohesion and affiliation, and (c) elicit feelings of reward. I outline how these characteristics relate to theories of music cognition and empirical findings in psychology and neuroscience research. I also explain the specifics of musical self-enhancement and how it differs from music's other regulatory functions such as mood- and emotion regulation. My aim in introducing the notion of musical self-enhancement is to broaden our understanding of how music functions as an environmental resource entailing access to unique affective states and how musical experiences are co-constituted by both the agent and the sonic environment. This specific use of music for self enhancement can be regarded as a form of affective niche construction, providing the external conditions in which people can experience themselves more positively and maintain high self-esteem. PMID- 26834676 TI - Loss-Chasing, Alexithymia, and Impulsivity in a Gambling Task: Alexithymia as a Precursor to Loss-Chasing Behavior When Gambling. AB - OBJECTIVE: To examine the relationship between loss-chasing, the propensity to continue gambling to recover from losses, alexithymia, a personality trait associated poor emotional processing and impulsivity, the tendency to act quickly without reflection or consideration of the consequences. METHOD: Two experiments are reported (E1: N = 60, Males, 11; Age, 21.6 years. E2: N = 49, Males, 22; Age, 21.1 years). In experiment 1, two groups (low alexithymia, high alexithymia) completed the Cambridge Gambling Task (CGT). Loss-chasing behavior was investigated. In experiment 2, both alexithymia (low, high) and impulsivity (low, high) were examined also using the CGT. A further change was the order of bet proportion from ascending to descending. RESULTS: Experiment 1 shows loss-chasing behavior in participants high in alexithymia but not those low in alexithymia ([Formula: see text]). Experiment 2 shows loss-chasing behavior in participants both low and high in alexithymia but it was greater for participants high in alexithymia ([Formula: see text] = 0.09). The effect of impulsivity was not statistically significant ([Formula: see text] = 0.01). Loss-chasing behavior was correlated with the emotional facets of alexithymia but not the cognitive facet. CONCLUSIONS: Alexithymia is a precursor to loss-chasing when gambling and loss chasing reflects the cognitive and emotional aspects of gambling. Specifically, the tendency to loss-chase depends on the need to recoup previous losses and failure to process the emotional consequences of those losses. PMID- 26834677 TI - Processing Preference Toward Object-Extracted Relative Clauses in Mandarin Chinese by L1 and L2 Speakers: An Eye-Tracking Study. AB - The current study employed an eye-movement technique with an attempt to explore the reading patterns for the two types of Chinese relative clauses, subject extracted relative clauses (SRCs) and object-extracted relative clauses (ORCs), by native speakers (L1), and Japanese learners (L2) of Chinese. The data were analyzed in terms of gaze duration, regression path duration, and regression rate on the two critical regions, head noun, and embedded verb. The results indicated that both the L1 and L2 participants spent less time on the head nouns in ORCs than in SRCs. Also, the L2 participants spent less time on the embedded verbs in ORCs than in SRCs and their regression rate for embedded verbs was generally lower in ORCs than in SRC. The findings showed that the participants experienced less processing difficulty in ORCs than SRCs. These results suggest an ORC preference in L1 and L2 speakers of Chinese, which provides evidence in support of linear distance hypothesis and implies that the syntactic nature of Chinese is at play in the RC processing. PMID- 26834679 TI - Editorial: Development of Executive Function during Childhood. PMID- 26834678 TI - Effects of Divided Attention at Retrieval on Conceptual Implicit Memory. AB - This study investigated whether conceptual implicit memory is sensitive to process-specific interference at the time of retrieval. Participants performed the implicit memory test of category exemplar generation (CEG; Experiments 1 and 3), or the matched explicit memory test of category-cued recall (Experiment 2), both of which are conceptually driven memory tasks, under one of two divided attention (DA) conditions in which participants simultaneously performed a distracting task. The distracting task was either syllable judgments (dissimilar processes), or semantic judgments (similar processes) on unrelated words. Compared to full attention (FA) in which no distracting task was performed, DA had no effect on CEG priming overall, but reduced category-cued recall similarly regardless of distractor task. Analyses of distractor task performance also revealed differences between implicit and explicit memory retrieval. The evidence suggests that, whereas explicit memory retrieval requires attentional resources and is disrupted by semantic and phonological distracting tasks, conceptual implicit memory is automatic and unaffected even when distractor and memory tasks involve similar processes. PMID- 26834682 TI - Commentary: Cognitive reflection vs. calculation in decision making. PMID- 26834680 TI - Increased Event-Related Potentials and Alpha-, Beta-, and Gamma-Activity Associated with Intentional Actions. AB - OBJECTIVE: Internally guided actions are defined as being purposeful, self generated and offering choices between alternatives. Intentional actions are essential to reach individual goals. In previous empirical studies, internally guided actions were predominantly related to functional responses in frontal and parietal areas. The aim of the present study was to distinguish event-related potentials and oscillatory responses of intentional actions and externally guided actions. In addition, we compared neurobiological findings of the decision which action to perform with those referring to the decision whether or not to perform an action. METHODS: Twenty-eight subjects participated in adapted go/nogo paradigms, including a voluntary selection condition allowing participants to (1) freely decide whether to press the response button or (2) to decide whether they wanted to press the response button with the right index finger or the left index finger. RESULTS: The reaction times were increased when participants freely decided whether and how they wanted to respond compared to the go condition. Intentional processes were associated with a fronto-centrally located N2 and P3 potential. N2 and P3 amplitudes were increased during intentional actions compared to instructed responses (go). In addition, increased activity in the alpha-, beta- and gamma-frequency range was shown during voluntary behavior rather than during externally guided responses. CONCLUSION: These results may indicate that an additional cognitive process is needed for intentional actions compared to instructed behavior. However, the neural responses were comparatively independent of the kind of decision that was made (1) decision which action to perform; (2) decision whether or not to perform an action). SIGNIFICANCE: The study demonstrates the importance of fronto-central alpha-, beta-, and gamma oscillations for voluntary behavior. PMID- 26834681 TI - Addressing Stereotype Threat is Critical to Diversity and Inclusion in Organizational Psychology. AB - Recently researchers have debated the relevance of stereotype threat to the workplace. Critics have argued that stereotype threat is not relevant in high stakes testing such as in personnel selection. We and others argue that stereotype threat is highly relevant in personnel selection, but our review focused on underexplored areas including effects of stereotype threat beyond test performance and the application of brief, low-cost interventions in the workplace. Relevant to the workplace, stereotype threat can reduce domain identification, job engagement, career aspirations, and receptivity to feedback. Stereotype threat has consequences in other relevant domains including leadership, entrepreneurship, negotiations, and competitiveness. Several institutional and individual level intervention strategies that have been field tested and are easy to implement show promise for practitioners including: addressing environmental cues, valuing diversity, wise feedback, organizational mindsets, reattribution training, reframing the task, values-affirmation, utility value, belonging, communal goal affordances, interdependent worldviews, and teaching about stereotype threat. This review integrates criticisms and evidence into one accessible source for practitioners and provides recommendations for implementing effective, low-cost interventions in the workplace. PMID- 26834683 TI - Contribution of Embodiment to Solving the Riddle of Infantile Amnesia. AB - At least since the late nineteenth century, researchers have sought an explanation for infantile amnesia (IA)-the lack of autobiographical memories dating from early childhood-and childhood amnesia (CA), faster forgetting of events up until the age of about seven. Evidence suggests that IA occurs across altricial species, and a number of studies using animal models have converged on the hypothesis that maturation of the hippocampus is an important factor. But why does the hippocampus mature at one time and not another, and how does that maturation relate to memory? Our hypothesis is rooted in theories of embodied cognition, and it provides an explanation both for hippocampal development and the end of IA. Specifically, the onset of locomotion prompts the alignment of hippocampal place cells and grid cells to the environment, which in turn facilitates the ontogeny of long-term episodic memory and the end of IA. That is, because the animal can now reliably discriminate locations, location becomes a stable cue for memories. Furthermore, as the mode of human locomotion shifts from crawling to walking, there is an additional shift in the alignment of the hippocampus that marks the beginning of adult-like episodic memory and the end of CA. Finally, given a reduction in self-locomotion and exploration with aging, the hypothesis suggests a partial explanation for cognitive decline with aging. PMID- 26834684 TI - The Responders' Gender Stereotypes Modulate the Strategic Decision-Making of Proposers Playing the Ultimatum Game. AB - Despite the wealth of studies investigating factors affecting decisions, not much is known about the impact of stereotypical beliefs on strategic economic decision making. In the present study, we used the ultimatum game paradigm to investigate how participants playing as proposer modulate their strategic economic behavior, according to their game counterparts' stereotypical identity (i.e., responders). The latter were introduced to the participants using occupational role nouns stereotypically marked with gender paired with feminine or masculine proper names (e.g., linguist-Anna; economist-David; economist-Cristina; linguist-Leonardo). When playing with male-stereotyped responders, proposers quickly applied the equity rule, behaving fairly, while they adopted a strategic behavior with responders characterized by female stereotypes. They were also longer to make their offers to female than to male responders but both kinds of responders received comparable offers, suggesting a greater cognitive effort to treat females as equally as males. The present study explicitly demonstrates that gender stereotypical information affect strategic economic decision-making and highlights a possible evolution of gender discrimination into a more insidious discrimination toward individuals with female characteristics. PMID- 26834685 TI - Social Daydreaming and Adjustment: An Experience-Sampling Study of Socio Emotional Adaptation During a Life Transition. AB - Estimates suggest that up to half of waking life is spent daydreaming; that is, engaged in thought that is independent of, and unrelated to, one's current task. Emerging research indicates that daydreams are predominately social suggesting that daydreams may serve socio-emotional functions. Here we explore the functional role of social daydreaming for socio-emotional adjustment during an important and stressful life transition (the transition to university) using experience-sampling with 103 participants over 28 days. Over time, social daydreams increased in their positive characteristics and positive emotional outcomes; specifically, participants reported that their daydreams made them feel more socially connected and less lonely, and that the content of their daydreams became less fanciful and involved higher quality relationships. These characteristics then predicted less loneliness at the end of the study, which, in turn was associated with greater social adaptation to university. Feelings of connection resulting from social daydreams were also associated with less emotional inertia in participants who reported being less socially adapted to university. Findings indicate that social daydreaming is functional for promoting socio-emotional adjustment to an important life event. We highlight the need to consider the social content of stimulus-independent cognitions, their characteristics, and patterns of change, to specify how social thoughts enable socio-emotional adaptation. PMID- 26834686 TI - Investigation of Biases and Compensatory Strategies Using a Probabilistic Variant of the Wisconsin Card Sorting Test. AB - The Wisconsin Card Sorting Test (WCST) evaluates a subject's ability to shift to a new pattern of behavior in response to the presentation of unexpected negative feedback. The present study introduces a novel version of the traditional WCST by integrating a probabilistic component into its traditional rule shifting to add uncertainty to the task, as well as the option to forage for information during any particular trial. These changes transformed a task that is trivial for neurotypical individuals into a challenging environment useful for evaluating biases and compensatory strategizing. Sixty subjects performed the probabilistic WCST at four uncertainty levels to determine the effect of uncertainty on subject performance and strategy. Results revealed that increasing the level of uncertainty during a run of trials correlated with a reduction in rational strategizing in favor of both random choice and information foraging, evoking biases and suboptimal strategies such as satisfaction of search, negativity bias, and probability matching. PMID- 26834687 TI - Keep Calm and Comp. Cog. On. Commentary: A crisis in comparative psychology: where have all the undergraduates gone? PMID- 26834688 TI - Learning Linear Spatial-Numeric Associations Improves Accuracy of Memory for Numbers. AB - Memory for numbers improves with age and experience. One potential source of improvement is a logarithmic-to-linear shift in children's representations of magnitude. To test this, Kindergartners and second graders estimated the location of numbers on number lines and recalled numbers presented in vignettes (Study 1). Accuracy at number-line estimation predicted memory accuracy on a numerical recall task after controlling for the effect of age and ability to approximately order magnitudes (mapper status). To test more directly whether linear numeric magnitude representations caused improvements in memory, half of children were given feedback on their number-line estimates (Study 2). As expected, learning linear representations was again linked to memory for numerical information even after controlling for age and mapper status. These results suggest that linear representations of numerical magnitude may be a causal factor in development of numeric recall accuracy. PMID- 26834690 TI - "When" Does Picture Naming Take Longer Than Word Reading? AB - Differences between the cognitive processes involved in word reading and picture naming are well established (e.g., visual or lexico-semantic stages). Still, it is commonly thought that retrieval of phonological forms is shared across tasks. We report a test of this second hypothesis based on the time course of electroencephalographic (EEG) neural activity, reasoning that similar EEG patterns might index similar processing stages. Seventeen participants named objects and read aloud the corresponding words while their behavior and EEG activity were recorded. The latter was analyzed from stimulus onset onward (stimulus-locked analysis) and from response onset backward (response-locked analysis), using non-parametric statistics and the spatio-temporal segmentation of ERPs. Behavioral results confirmed that reading entails shorter latencies than naming. The analysis of EEG activity within the stimulus-to-response period allowed to distinguish three phases, broadly successive. Early on, we observed identical distribution of electric field potentials (i.e., topographies) albeit with large amplitude divergences between tasks. Then, we observed sustained cross task differences in topographies accompanied by extended amplitude differences. Finally, the two tasks again revealed the same topographies, with significant cross-task delays in their onsets and offsets, and still significant amplitude differences. In the response-locked ERPs, the common topography displayed an offset closer to response articulation in word reading compared with picture naming, that is the transition between the offset of this shared map and the onset of articulation was significantly faster in word reading. The results suggest that the degree of cross-task similarity varies across time. The first phase suggests similar visual processes of variable intensity and time course across tasks, while the second phase suggests marked differences. Finally, similarities and differences within the third phase are compatible with a shared processing stage (likely phonological processes) with different temporal properties (onset/offset) across tasks. Overall, our results provide an overview of when, between stimulus and response, word reading and picture naming are subtended by shared- versus task-specific neural signatures. This in turn is suggestive of when the two tasks involve similar vs. different cognitive processes. PMID- 26834689 TI - Music and Dyslexia: A New Musical Training Method to Improve Reading and Related Disorders. AB - Numerous arguments in the recent neuroscientific literature support the use of musical training as a therapeutic tool among the arsenal already available to therapists and educators for treating children with dyslexia. In the present study, we tested the efficacy of a specially-designed Cognitivo-Musical Training (CMT) method based upon three principles: (1) music-language analogies: training dyslexics with music could contribute to improve brain circuits which are common to music and language processes; (2) the temporal and rhythmic features of music, which could exert a positive effect on the multiple dimensions of the "temporal deficit" characteristic of some types of dyslexia; and (3) cross-modal integration, based on converging evidence of impaired connectivity between brain regions in dyslexia and related disorders. Accordingly, we developed a series of musical exercises involving jointly and simultaneously sensory (visual, auditory, somatosensory) and motor systems, with special emphasis on rhythmic perception and production in addition to intensive training of various features of the musical auditory signal. Two separate studies were carried out, one in which dyslexic children received intensive musical exercises concentrated over 18 h during 3 consecutive days, and the other in which the 18 h of musical training were spread over 6 weeks. Both studies showed significant improvements in some untrained, linguistic and non-linguistic variables. The first one yielded significant improvement in categorical perception and auditory perception of temporal components of speech. The second study revealed additional improvements in auditory attention, phonological awareness (syllable fusion), reading abilities, and repetition of pseudo-words. Importantly, most improvements persisted after an untrained period of 6 weeks. These results provide new additional arguments for using music as part of systematic therapeutic and instructional practice for dyslexic children. PMID- 26834691 TI - Analyzing Two-Phase Single-Case Data with Non-overlap and Mean Difference Indices: Illustration, Software Tools, and Alternatives. AB - Two-phase single-case designs, including baseline evaluation followed by an intervention, represent the most clinically straightforward option for combining professional practice and research. However, unless they are part of a multiple baseline schedule, such designs do not allow demonstrating a causal relation between the intervention and the behavior. Although the statistical options reviewed here cannot help overcoming this methodological limitation, we aim to make practitioners and applied researchers aware of the available appropriate options for extracting maximum information from the data. In the current paper, we suggest that the evaluation of behavioral change should include visual and quantitative analyses, complementing the substantive criteria regarding the practical importance of the behavioral change. Specifically, we emphasize the need to use structured criteria for visual analysis, such as the ones summarized in the What Works Clearinghouse Standards, especially if such criteria are complemented by visual aids, as illustrated here. For quantitative analysis, we focus on the non-overlap of all pairs and the slope and level change procedure, as they offer straightforward information and have shown reasonable performance. An illustration is provided of the use of these three pieces of information: visual, quantitative, and substantive. To make the use of visual and quantitative analysis feasible, open source software is referred to and demonstrated. In order to provide practitioners and applied researchers with a more complete guide, several analytical alternatives are commented on pointing out the situations (aims, data patterns) for which these are potentially useful. PMID- 26834692 TI - Regional Interplay for Temporal Processing in Parkinson's Disease: Possibilities and Challenges. AB - Parkinson's disease (PD) is primarily associated with two dominant features: cardinal motor symptoms and the loss of cells in the substantia nigra pars compacta of the basal ganglia. Consequently, these aspects are major foci in PD related research. However, PD is a neurodegenerative disease, which progressively affects multiple brain regions outside the basal ganglia and leads to symptoms outside the motor domain. Much less is known about the individual contribution of these secondary regions, their interplay and interaction with the basal ganglia, and the respective network dynamics in the overall manifestation of PD. These regions include classical motor structures such as the cerebellum and the supplementary motor area (SMA). However, just as the basal ganglia, these regions display a fine-grained microarchitecture, which supports sensory and sensorimotor functions. One such function is temporal processing, which has been ascribed to a network comprising all of these regions. On the one hand, pathological changes in this temporal processing network may be part and parcel of motor and non-motor symptoms in PD. On the other hand, a better understanding of the role of each network node may offer a novel perspective on compensatory mechanisms, therapeutic interventions, as well as the heterogeneity and individual differences associated with PD. We unfold this perspective by relating the neural foundations and functional implications of temporal processing to pathophysiological and neurofunctional changes characteristic of PD. PMID- 26834693 TI - Antisaccadic Eye Movements Are Correlated with Corpus Callosum White Matter Mean Diffusivity, Stroop Performance, and Symptom Burden in Mild Traumatic Brain Injury and Concussion. AB - Antisaccades are thought to involve higher level inputs from neural centers involved in rapid eye movement inhibition and control. Previous work has demonstrated that performance on the antisaccade task can help in the assessment of injury in acute and/or chronic mild traumatic brain injury (mTBI). In this exploratory study, we performed cross-sectional and longitudinal comparisons of rapid eye movement, followed by correlations of antisaccade performance with assessments of symptom burden, diffusion tensor imaging, and a neuropsychological test of response inhibition. Significant deficits in antisaccade median latency, F(2, 31) = 3.65, p = 0.04 and prosaccade error mean duration, F(2, 31) = 3.63, p = 0.04 were found between patient groups and controls: the former was correlated with loss of white matter integrity in the splenium of the corpus callosum in acute mTBI, rho = 0.90, p = 0.0005. Furthermore, increased antisaccade median latency was also correlated with poor performance on an executive functioning task, r (2) = 0.439, p = 0.03, and greater symptom burden, r (2) = 0.480, p = 0.02 in the acute mTBI patients. Our preliminary research suggests that the antisaccade task could be useful as a neurological marker for mTBI and concussion, but more work is required. PMID- 26834694 TI - Neurorehabilitation for Multiple Sclerosis Patients with Emotional Dysfunctions. AB - Depression frequently develops in multiple sclerosis (MS) patients, exacerbating the manifestations of the disease and making its management challenging. To date, no consensus has been reached regarding effective treatments for these sufferers due to limited understanding regarding the underlying mechanisms responsible for emotional disorders that are highly comorbid with this disease. There is an urgent need to rethink current treatment options for these patients. This article aims to optimize the treatment outcomes and improve the quality of life for MS patients. Based on an in-depth and critical review of the current literature, we provide a neurorehabilitative framework that explains possible regulatory mechanisms underlying the emotional symptoms highly developed in MS. This article offers practical knowledge and therapeutic strategies to optimize the treatment options in the current care system for MS, as well as for other disabling diseases. PMID- 26834696 TI - A Technological Review of the Instrumented Footwear for Rehabilitation with a Focus on Parkinson's Disease Patients. AB - In this review article, we summarize systems for gait rehabilitation based on instrumented footwear and present a context of their usage in Parkinson's disease (PD) patients' auditory and haptic rehabilitation. We focus on the needs of PD patients, but since only a few systems were made with this purpose, we go through several applications used in different scenarios when gait detection and rehabilitation are considered. We present developments of the designs, possible improvements, and software challenges and requirements. We conclude that in order to build successful systems for PD patients' gait rehabilitation, technological solutions from several studies have to be applied and combined with knowledge from auditory and haptic cueing. PMID- 26834695 TI - The Role of Medical Imaging in the Recharacterization of Mild Traumatic Brain Injury Using Youth Sports as a Laboratory. AB - The short- and long-term impact of mild traumatic brain injury (TBI) is an increasingly vital concern for both military and civilian personnel. Such injuries produce significant social and financial burdens and necessitate improved diagnostic and treatment methods. Recent integration of neuroimaging and biomechanical studies in youth collision-sport athletes has revealed that significant alterations in brain structure and function occur even in the absence of traditional clinical markers of "concussion." While task performance is maintained, athletes exposed to repetitive head accelerations exhibit structural changes to the underlying white matter, altered glial cell metabolism, aberrant vascular response, and marked changes in functional network behavior. Moreover, these changes accumulate with accrued years of exposure, suggesting a cumulative trauma mechanism that may culminate in categorization as "concussion" and long term neurological deficits. The goal of this review is to elucidate the role of medical imaging in recharacterizing TBI, as a whole, to better identify at-risk individuals and improve the development of preventative and interventional approaches. PMID- 26834697 TI - Synaptic Mechanisms of Blast-Induced Brain Injury. AB - Blast wave-induced traumatic brain injury (TBI) is one of the most common injuries to military personnel. Brain tissue compression/tension due to blast induced cranial deformations and shear waves due to head rotation may generate diffuse micro-damage to neuro-axonal structures and trigger a cascade of neurobiological events culminating in cognitive and neurodegenerative disorders. Although diffuse axonal injury is regarded as a signature wound of mild TBI (mTBI), blast loads may also cause synaptic injury wherein neuronal synapses are stretched and sheared. This synaptic injury may result in temporary disconnect of the neural circuitry and transient loss in neuronal communication. We hypothesize that mTBI symptoms such as loss of consciousness or dizziness, which start immediately after the insult, could be attributed to synaptic injury. Although empirical evidence is beginning to emerge; the detailed mechanisms underlying synaptic injury are still elusive. Coordinated in vitro-in vivo experiments and mathematical modeling studies can shed light into the synaptic injury mechanisms and their role in the potentiation of mTBI symptoms. PMID- 26834698 TI - Eye-Movement Training Results in Changes in qEEG and NIH Stroke Scale in Subjects Suffering from Acute Middle Cerebral Artery Ischemic Stroke: A Randomized Control Trial. AB - CONTEXT: Eye-movement training (EMT) can induce altered brain activation and change the functionality of saccades with changes of the brain in general. OBJECTIVE: To determine if EMT would result in changes in quantitative electroencephalogram (qEEG) and NIH Stroke Scale (NIHSS) in patients suffering from acute middle cerebral artery (MCA) infarction. Our hypothesis is that there would be positive changes in qEEG and NIHSS after EMT in patients suffering from acute MCA ischemic stroke. DESIGN: Double-blind randomized controlled trial. SETTING AND PARTICIPANTS: Thirty-four subjects with acute MCA ischemic stroke treated at university affiliated hospital intensive care unit. INTERVENTIONS: Subjects were randomized into a "control" group treated only with aspirin (125 mg/day) and a "treatment" group treated with aspirin (125 mg/day) and a subject specific EMT. MAIN OUTCOME MEASURES: Delta-alpha ratio, power ratio index, and the brain symmetry index calculated by qEEG and NIHSS. RESULTS: There was strong statistical and substantive significant improvement in all outcome measures for the group of stroke patients undergoing EMT. Such improvement was not observed for the "control" group, and there were no adverse effects. CONCLUSION: The addition of EMT to a MCA ischemic stroke treatment paradigm has demonstrated statistically significant changes in outcome measures and is a low cost, safe, and effective complement to standard treatment. PMID- 26834699 TI - Absence of Rotation Perception during Warm Water Caloric Irrigation in Some Seniors with Postural Instability. AB - Falls in seniors are a major public health problem. Falls lead to fear of falling, reduced mobility, and decreased quality of life. Vestibular dysfunction is one of the fall risk factors. The relationship between objective measures of vestibular responses and age has been studied. However, the effects of age on vestibular perception during caloric stimulation have not been studied. Twenty senior subjects were included in the study, and separated in two groups: 10 seniors reporting postural instability (PI) and exhibiting absence of vestibular perception when they tested with caloric stimulation and 10 sex- and age-matched seniors with no such problems (controls). We assessed vestibular perception on a binary rating scale during the warm irrigation of the caloric test. The function of the various vestibular receptors was assessed using video head impulse test (vHIT), caloric tests, and cervical and ocular vestibular-evoked myogenic potentials. The Equitest was used to evaluate balance. No horizontal canal dysfunction assessed using both caloric test and vHIT was detected in either group. No significant difference was detected between PI and control groups for the peak SPV of caloric-induced ocular nystagmus or for the HVOR gain. All the controls perceived rotation when the maximal SPV during warm irrigation was equal to or >=15 degrees /s. None of the subjects in the PI group perceived rotation even while the peak SPV exceeded 15 degrees /s, providing objective evidence of normal peripheral horizontal canal function. All the PI group had abnormal Equitest results, particularly in the two last conditions. These investigations show for the first time that vestibular perception can be absent during a caloric test despite normal horizontal canal function. We call this as dissociation vestibular neglect. Patients with poor vestibular perception may not be aware of postural perturbations and so will not correct for them. Thus, falls in the elderly may result, among other factors, from a vestibular neglect due to an inappropriate central processing of normal vestibular peripheral inputs. That is, failure to perceive rotation during caloric testing when the SPV is >15 degrees /s, should prompt the clinician to envisage preventive actions to avoid future falls such as rehabilitation. PMID- 26834700 TI - GIT2 Acts as a Systems-Level Coordinator of Neurometabolic Activity and Pathophysiological Aging. AB - Aging represents one of the most complicated and highly integrated somatic processes. Healthy aging is suggested to rely upon the coherent regulation of hormonal and neuronal communication between the central nervous system and peripheral tissues. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity and therefore likely coordinates multiple systems in the aging process. We previously identified, in hypothalamic and peripheral tissues, the G protein-coupled receptor kinase interacting protein 2 (GIT2) as a stress response and aging regulator. As metabolic status profoundly affects aging trajectories, we investigated the role of GIT2 in regulating metabolic activity. We found that genomic deletion of GIT2 alters hypothalamic transcriptomic signatures related to diabetes and metabolic pathways. Deletion of GIT2 reduced whole animal respiratory exchange ratios away from those related to primary glucose usage for energy homeostasis. GIT2 knockout (GIT2KO) mice demonstrated lower insulin secretion levels, disruption of pancreatic islet beta cell mass, elevated plasma glucose, and insulin resistance. High-dimensionality transcriptomic signatures from islets isolated from GIT2KO mice indicated a disruption of beta cell development. Additionally, GIT2 expression was prematurely elevated in pancreatic and hypothalamic tissues from diabetic-state mice (db/db), compared to age-matched wild type (WT) controls, further supporting the role of GIT2 in metabolic regulation and aging. We also found that the physical interaction of pancreatic GIT2 with the insulin receptor and insulin receptor substrate 2 was diminished in db/db mice compared to WT mice. Therefore, GIT2 appears to exert a multidimensional "keystone" role in regulating the aging process by coordinating somatic responses to energy deficits. PMID- 26834702 TI - Knowledge Gaps in Rodent Pancreas Biology: Taking Human Pluripotent Stem Cell Derived Pancreatic Beta Cells into Our Own Hands. AB - In the field of stem cell biology and diabetes, we and others seek to derive mature and functional human pancreatic beta cells for disease modeling and cell replacement therapy. Traditionally, knowledge gathered from rodents is extended to human pancreas developmental biology research involving human pluripotent stem cells (hPSCs). While much has been learnt from rodent pancreas biology in the early steps toward Pdx1(+) pancreatic progenitors, much less is known about the transition toward Ngn3(+) pancreatic endocrine progenitors. Essentially, the later steps of pancreatic beta cell development and maturation remain elusive to date. As a result, the most recent advances in the stem cell and diabetes field have relied upon combinatorial testing of numerous growth factors and chemical compounds in an arbitrary trial-and-error fashion to derive mature and functional human pancreatic beta cells from hPSCs. Although this hit-or-miss approach appears to have made some headway in maturing human pancreatic beta cells in vitro, its underlying biology is vaguely understood. Therefore, in this mini review, we discuss some of these late-stage signaling pathways that are involved in human pancreatic beta cell differentiation and highlight our current understanding of their relevance in rodent pancreas biology. Our efforts here unravel several novel signaling pathways that can be further studied to shed light on unexplored aspects of rodent pancreas biology. New investigations into these signaling pathways are expected to advance our knowledge in human pancreas developmental biology and to aid in the translation of stem cell biology in the context of diabetes treatments. PMID- 26834704 TI - Structural Iron (II) of Basaltic Glass as an Energy Source for Zetaproteobacteria in an Abyssal Plain Environment, Off the Mid Atlantic Ridge. AB - To explore the capability of basaltic glass to support the growth of chemosynthetic microorganisms, complementary in situ and in vitro colonization experiments were performed. Microbial colonizers containing synthetic tholeitic basaltic glasses, either enriched in reduced or oxidized iron, were deployed off axis from the Mid Atlantic Ridge on surface sediments of the abyssal plain (35 degrees N; 29 degrees W). In situ microbial colonization was assessed by sequencing of the 16S rRNA gene and basaltic glass alteration was characterized using Scanning Electron Microscopy, micro-X-ray Absorption Near Edge Structure at the Fe-K-edge and Raman microspectroscopy. The colonized surface of the reduced basaltic glass was covered by a rind of alteration made of iron-oxides trapped in a palagonite-like structure with thicknesses up to 150 MUm. The relative abundance of the associated microbial community was dominated (39% of all reads) by a single operational taxonomic unit (OTU) that shared 92% identity with the iron-oxidizer Mariprofundus ferrooxydans PV-1. Conversely, the oxidized basaltic glass showed the absence of iron-oxides enriched surface deposits and correspondingly there was a lack of known iron-oxidizing bacteria in the inventoried diversity. In vitro, a similar reduced basaltic glass was incubated in artificial seawater with a pure culture of the iron-oxidizing M. ferrooxydans DIS-1 for 2 weeks, without any additional nutrients or minerals. Confocal Laser Scanning Microscopy revealed that the glass surface was covered by twisted stalks characteristic of this iron-oxidizing Zetaproteobacteria. This result supported findings of the in situ experiments indicating that the Fe(II) present in the basalt was the energy source for the growth of representatives of Zetaproteobacteria in both the abyssal plain and the in vitro experiment. In accordance, the surface alteration rind observed on the reduced basaltic glass incubated in situ could at least partly result from their activity. PMID- 26834701 TI - Fibroblast Growth Factor Signaling in Metabolic Regulation. AB - The prevalence of obesity is a growing health problem. Obesity is strongly associated with several comorbidities, such as non-alcoholic fatty liver disease, certain cancers, insulin resistance, and type 2 diabetes, which all reduce life expectancy and life quality. Several drugs have been put forward in order to treat these diseases, but many of them have detrimental side effects. The unexpected role of the family of fibroblast growth factors in the regulation of energy metabolism provides new approaches to the treatment of metabolic diseases and offers a valuable tool to gain more insight into metabolic regulation. The known beneficial effects of FGF19 and FGF21 on metabolism, together with recently discovered similar effects of FGF1 suggest that FGFs and their derivatives carry great potential as novel therapeutics to treat metabolic conditions. To facilitate the development of new therapies with improved targeting and minimal side effects, a better understanding of the molecular mechanism of action of FGFs is needed. In this review, we will discuss what is currently known about the physiological roles of FGF signaling in tissues important for metabolic homeostasis. In addition, we will discuss current concepts regarding their pharmacological properties and effector tissues in the context of metabolic disease. Also, the recent progress in the development of FGF variants will be reviewed. Our goal is to provide a comprehensive overview of the current concepts and consensuses regarding FGF signaling in metabolic health and disease and to provide starting points for the development of FGF-based therapies against metabolic conditions. PMID- 26834703 TI - microRNAs as Potential Biomarkers in Adrenocortical Cancer: Progress and Challenges. AB - Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis and limited therapeutic options. Over the last decade, pan-genomic analyses of genetic and epigenetic alterations and genome-wide expression profile studies allowed major advances in the understanding of the molecular genetics of ACC. Besides the well-known dysfunctional molecular pathways in adrenocortical tumors, such as the IGF2 pathway, the Wnt pathway, and TP53, high-throughput technologies enabled a more comprehensive genomic characterization of adrenocortical cancer. Integration of expression profile data with exome sequencing, SNP array analysis, methylation, and microRNA (miRNA) profiling led to the identification of subgroups of malignant tumors with distinct molecular alterations and clinical outcomes. miRNAs post-transcriptionally silence their target gene expression either by degrading mRNA or by inhibiting translation. Although our knowledge of the contribution of deregulated miRNAs to the pathogenesis of ACC is still in its infancy, recent studies support their relevance in gene expression alterations in these tumors. Some miRNAs have been shown to carry potential diagnostic and prognostic values, while others may be good candidates for therapeutic interventions. With the emergence of disease-specific blood-borne miRNAs signatures, analyses of small cohorts of patients with ACC suggest that circulating miRNAs represent promising non-invasive biomarkers of malignancy or recurrence. However, some technical challenges still remain, and most of the miRNAs reported in the literature have not yet been validated in sufficiently powered and longitudinal studies. In this review, we discuss the current knowledge regarding the deregulation of tumor-associated and circulating miRNAs in ACC patients, while emphasizing their potential significance in pathogenic pathways in light of recent insights into the role of miRNAs in shaping the tumor microenvironment. PMID- 26834705 TI - Fatal Leishmaniasis in the Absence of TNF Despite a Strong Th1 Response. AB - Induction of inducible nitric oxide synthase in mononuclear phagocytes by IFN gamma and innate tumor necrosis factor (TNF) provide the basis for an effective immune response to the intracellular parasite Leishmania (L.) major. In previous experiments, we observed a fatal visceral form of leishmaniasis in L. major infected C57BL/6 TNF(-/-) mice. To further delineate the protective function of TNF and its receptor requirements, we comparatively assessed L. major-infected C57BL/6 mice that were either deficient for membrane and soluble TNF (Tnf (-) (/) (-)), for soluble TNF alone (memTnf(Delta/Delta) ), or the TNF receptors type 1 (Tnfr1 (-) (/) (-)) or type 2 (Tnfr2 (-) (/) (-)). We detected locally and systemically increased levels of the cytokine IFN-gamma in the absence of the TNF TNFR1-signaling pathway. An analysis of transcription factors and cytokines revealed that activated Tnf (-) (/) (-) CD4(+) T cells displayed a highly active Th1 phenotype with a strong usage of the T cell receptor Vbeta5.1/2. From these data we conclude that the fatal outcome of L. major infection in Tnf (-) (/) (-) mice does not result from a skewed or deficient Th1 differentiation. PMID- 26834706 TI - Bacterial Vaginosis Biofilms: Challenges to Current Therapies and Emerging Solutions. AB - Bacterial vaginosis (BV) is the most common genital tract infection in women during their reproductive years and it has been associated with serious health complications, such as preterm delivery and acquisition or transmission of several sexually transmitted agents. BV is characterized by a reduction of beneficial lactobacilli and a significant increase in number of anaerobic bacteria, including Gardnerella vaginalis, Atopobium vaginae, Mobiluncus spp., Bacteroides spp. and Prevotella spp.. Being polymicrobial in nature, BV etiology remains unclear. However, it is certain that BV involves the presence of a thick vaginal multi-species biofilm, where G. vaginalis is the predominant species. Similar to what happens in many other biofilm-related infections, standard antibiotics, like metronidazole, are unable to fully eradicate the vaginal biofilm, which can explain the high recurrence rates of BV. Furthermore, antibiotic therapy can also cause a negative impact on the healthy vaginal microflora. These issues sparked the interest in developing alternative therapeutic strategies. This review provides a quick synopsis of the currently approved and available antibiotics for BV treatment while presenting an overview of novel strategies that are being explored for the treatment of this disorder, with special focus on natural compounds that are able to overcome biofilm associated antibiotic resistance. PMID- 26834708 TI - Bacterial Communities Vary between Sinuses in Chronic Rhinosinusitis Patients. AB - Chronic rhinosinusitis (CRS) is a common and potentially debilitating disease characterized by inflammation of the sinus mucosa for longer than 12 weeks. Bacterial colonization of the sinuses and its role in the pathogenesis of this disease is an ongoing area of research. Recent advances in culture-independent molecular techniques for bacterial identification have the potential to provide a more accurate and complete assessment of the sinus microbiome, however there is little concordance in results between studies, possibly due to differences in the sampling location and techniques. This study aimed to determine whether the microbial communities from one sinus could be considered representative of all sinuses, and examine differences between two commonly used methods for sample collection, swabs, and tissue biopsies. High-throughput DNA sequencing of the bacterial 16S rRNA gene was applied to both swab and tissue samples from multiple sinuses of 19 patients undergoing surgery for treatment of CRS. Results from swabs and tissue biopsies showed a high degree of similarity, indicating that swabbing is sufficient to recover the microbial community from the sinuses. Microbial communities from different sinuses within individual patients differed to varying degrees, demonstrating that it is possible for distinct microbiomes to exist simultaneously in different sinuses of the same patient. The sequencing results correlated well with culture-based pathogen identification conducted in parallel, although the culturing missed many species detected by sequencing. This finding has implications for future research into the sinus microbiome, which should take this heterogeneity into account by sampling patients from more than one sinus. PMID- 26834709 TI - Vertical Segregation and Phylogenetic Characterization of Ammonia-Oxidizing Bacteria and Archaea in the Sediment of a Freshwater Aquaculture Pond. AB - Pond aquaculture is the major freshwater aquaculture method in China. Ammonia oxidizing communities inhabiting pond sediments play an important role in controlling culture water quality. However, the distribution and activities of ammonia-oxidizing microbial communities along sediment profiles are poorly understood in this specific environment. Vertical variations in the abundance, transcription, potential ammonia oxidizing rate, and community composition of ammonia-oxidizing bacteria (AOB) and ammonia-oxidizing archaea (AOA) in sediment samples (0-50 cm depth) collected from a freshwater aquaculture pond were investigated. The concentrations of the AOA amoA gene were higher than those of the AOB by an order of magnitude, which suggested that AOA, as opposed to AOB, were the numerically predominant ammonia-oxidizing organisms in the surface sediment. This could be attributed to the fact that AOA are more resistant to low levels of dissolved oxygen. However, the concentrations of the AOB amoA mRNA were higher than those of the AOA by 2.5- to 39.9-fold in surface sediments (0-10 cm depth), which suggests that the oxidation of ammonia was mainly performed by AOB in the surface sediments, and by AOA in the deeper sediments, where only AOA could be detected. Clone libraries of AOA and AOB amoA sequences indicated that the diversity of AOA and AOB decreased with increasing depth. The AOB community consisted of two groups: the Nitrosospira and Nitrosomonas clusters, and Nitrosomonas were predominant in the freshwater pond sediment. All AOA amoA gene sequences in the 0-2 cm deep sediment were grouped into the Nitrososphaera cluster, while other AOA sequences in deeper sediments (10-15 and 20-25 cm depths) were grouped into the Nitrosopumilus cluster. PMID- 26834707 TI - Natural Antimicrobials and Oral Microorganisms: A Systematic Review on Herbal Interventions for the Eradication of Multispecies Oral Biofilms. AB - Oral diseases such as caries and periodontitis are mainly caused by microbial biofilms. Antibiotic therapy has reached its limits with regard to antimicrobial resistance, and new therapeutic measures utilizing natural phytochemicals are currently a focus of research. Hence, this systematic review provides a critical presentation of the antimicrobial effects of various medicinal herbs against in vitro, ex vivo, and in situ formed multispecies oral biofilms. Searches were performed in three English databases (PubMed, EMBASE, CAMbase) and the electronic archives of five German journals from the times of their establishment until October 10th, 2014, with the search terms "(plant extracts OR herbal extracts OR plant OR herb) AND (oral biofilm OR dental biofilm OR dental plaque OR oral disease OR dental disease)." The pooled data were assessed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA). Initially, 1848 articles were identified, out of which 585 full-text articles were screened, 149 articles were reevaluated for eligibility and finally, 14 articles met all inclusion criteria. The data of 14 reports disclosed enhanced antiadhesive and antibiofilm activity by the plant extracts obtained from Vitis vinifera, Pinus spp., Coffea canephora, Camellia sinensis, Vaccinium macrocarpon, Galla chinensis, Caesalpinia ferrea Martius, Psidium cattleianum, representative Brazilian plants and manuka honey. Overall, a positive correlation was revealed between herb-based therapies and elimination rates of all types of multispecies oral biofilms. In that context, integrating or even replacing conventional dental therapy protocols with herbal-inspired treatments can allow effective antimicrobial control of oral biofilms and thus, dental diseases. PMID- 26834710 TI - Recombination Does Not Hinder Formation or Detection of Ecological Species of Synechococcus Inhabiting a Hot Spring Cyanobacterial Mat. AB - Recent studies of bacterial speciation have claimed to support the biological species concept-that reduced recombination is required for bacterial populations to diverge into species. This conclusion has been reached from the discovery that ecologically distinct clades show lower rates of recombination than that which occurs among closest relatives. However, these previous studies did not attempt to determine whether the more-rapidly recombining close relatives within the clades studied may also have diversified ecologically, without benefit of sexual isolation. Here we have measured the impact of recombination on ecological diversification within and between two ecologically distinct clades (A and B') of Synechococcus in a hot spring microbial mat in Yellowstone National Park, using a cultivation-free, multi-locus approach. Bacterial artificial chromosome (BAC) libraries were constructed from mat samples collected at 60 degrees C and 65 degrees C. Analysis of multiple linked loci near Synechococcus 16S rRNA genes showed little evidence of recombination between the A and B' lineages, but a record of recombination was apparent within each lineage. Recombination and mutation rates within each lineage were of similar magnitude, but recombination had a somewhat greater impact on sequence diversity than mutation, as also seen in many other bacteria and archaea. Despite recombination within the A and B' lineages, there was evidence of ecological diversification within each lineage. The algorithm Ecotype Simulation identified sequence clusters consistent with ecologically distinct populations (ecotypes), and several hypothesized ecotypes were distinct in their habitat associations and in their adaptations to different microenvironments. We conclude that sexual isolation is more likely to follow ecological divergence than to precede it. Thus, an ecology-based model of speciation appears more appropriate than the biological species concept for bacterial and archaeal diversification. PMID- 26834711 TI - Fragments of Target Cells are Internalized into Retroviral Envelope Protein Expressing Cells during Cell-Cell Fusion by Endocytosis. AB - Retroviruses enter into host cells by fusion between viral and host cell membranes. Retroviral envelope glycoprotein (Env) induces the membrane fusion, and also mediates cell-cell fusion. There are two types of cell-cell fusions induced by the Env protein. Fusion-from-within is induced by fusion between viral fusogenic Env protein-expressing cells and susceptible cells, and virions induce fusion-from-without by fusion between adjacent cells. Although entry of ecotropic murine leukemia virus (E-MLV) requires host cell endocytosis, the involvement of endocytosis in cell fusion is unclear. By fluorescent microscopic analysis of the fusion-from-within, we found that fragments of target cells are internalized into Env-expressing cells. Treatment of the Env-expressing cells with an endocytosis inhibitor more significantly inhibited the cell fusion than that of the target cells, indicating that endocytosis in Env-expressing cells is required for the cell fusion. The endocytosis inhibitor also attenuated the fusion-from-without. Electron microscopic analysis suggested that the membrane fusion resulting in fusion-from-within initiates in endocytic membrane dents. This study shows that two types of the viral cell fusion both require endocytosis, and provides the cascade of fusion-from-within. PMID- 26834712 TI - Exploration of Microbial Diversity and Community Structure of Lonar Lake: The Only Hypersaline Meteorite Crater Lake within Basalt Rock. AB - Lonar Lake is a hypersaline and hyperalkaline soda lake and the only meteorite impact crater in the world situated in basalt rocks. Although culture-dependent studies have been reported, a comprehensive understanding of microbial community composition and structure in Lonar Lake remains elusive. In the present study, microbial community structure associated with Lonar Lake sediment and water samples was investigated using high-throughput sequencing. Microbial diversity analysis revealed the existence of diverse, yet largely consistent communities. Proteobacteria (30%), Actinobacteria (24%), Firmicutes (11%), and Cyanobacteria (5%) predominated in the sequencing survey, whereas Bacteroidetes (1.12%), BD1-5 (0.5%), Nitrospirae (0.41%), and Verrucomicrobia (0.28%) were detected in relatively minor abundances in the Lonar Lake ecosystem. Within the Proteobacteria phylum, the Gammaproteobacteria represented the most abundantly detected class (21-47%) within sediment samples, but only a minor population in the water samples. Proteobacteria and Firmicutes were found at significantly higher abundance (p >= 0.05) in sediment samples, whereas members of Actinobacteria, Candidate division TM7 and Cyanobacteria (p >= 0.05) were significantly abundant in water samples. Compared to the microbial communities of other hypersaline soda lakes, those of Lonar Lake formed a distinct cluster, suggesting a different microbial community composition and structure. Here we report for the first time, the difference in composition of indigenous microbial communities between the sediment and water samples of Lonar Lake. An improved census of microbial community structure in this Lake ecosystem provides a foundation for exploring microbial biogeochemical cycling and microbial function in hypersaline lake environments. PMID- 26834713 TI - Genomic Investigation of a Legionellosis Outbreak in a Persistently Colonized Hotel. AB - OBJECTIVES: A long-lasting legionellosis outbreak was reported between November 2011 and July 2012 in a hotel in Calpe (Spain) affecting 44 patients including six deaths. Intensive epidemiological and microbiological investigations were performed in order to detect the reservoirs. METHODS: Clinical and environmental samples were tested for the presence and genetic characterization of Legionella pneumophila. Six of the isolates were subjected to whole-genome sequencing. RESULTS: Sequencing of 14 clinical and 260 environmental samples revealed sequence type (ST) 23 as the main responsible strain for the infections. This ST was found in the spa pool, from where it spread to other hotel public spaces, explaining the ST23 clinical cases, including guests who had not visited the spa. Uncultured clinical specimens showed profiles compatible with ST23, ST578, and mixed patterns. Profiles compatible with ST578 were obtained by direct sequencing from biofilm samples collected from the domestic water system, which provided evidence for the source of infection for non ST23 patients. Whole genome data from five ST23 strains and the identification of different STs and Legionella species showed that different hotel premises were likely colonized since the hotel opening thus explaining how different patients had been infected by distinct STs. CONCLUSIONS: Both epidemiological and molecular data are essential in the investigation of legionellosis outbreaks. Whole-genome sequencing data revealed significant intra-ST variability and allowed to make further inference on the short-term evolution of a local colonization of L. pneumophila. PMID- 26834715 TI - The Apoptotic Role of Metacaspase in Toxoplasma gondii. AB - Toxoplasma gondii is a major opportunistic pathogen that spreads in a range of animal species and human beings. Quite a few characterizations of apoptosis have been identified in T. gondii treated with apoptosis inducers, but the molecular mechanisms of the pathway are not clearly understood. Metacaspases are caspase like cysteine proteases that can be found in plants, fungi, and protozoa in which caspases are absent. Metacaspases are multifunctional proteases involved in apoptosis-like cell death, insoluble protein aggregate clearance, and cell proliferation. To investigate whether T. gondii metacaspase (TgMCA) is involved in the apoptosis of the parasites, we generated TgMCA mutant strains. Western blot analysis indicated that the autoproteolytic processing of TgMCA was the same as that for metacaspases of some other species. Indirect immunofluorescence assay (IFA) showed that TgMCA was dispersed throughout the cytoplasm and relocated to the nucleus when the parasites were exposed to the extracellular environment, which indicated the execution of its function in the nucleus. The number of apoptosis parasites was significantly diminished in the TgMCA knockout strain and increased in the TgMCA overexpression strain after treatment with extracellular buffer, as determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The lack of TgMCA did not affect the parasite propagation in vitro and virulence in vivo, suggesting that it is probably redundant in parasite propagation. But overexpression of TgMCA reduced the intracellular parasites growth in vitro. The TgMCA knockout strain showed more viability in extracellular buffer compared to the parental and overexpression lines. In this study, we demonstrated that TgMCA contributes to the apoptosis of T. gondii. PMID- 26834714 TI - Arbuscular Mycorrhizal Fungi as Natural Biofertilizers: Let's Benefit from Past Successes. AB - Arbuscular Mycorrhizal Fungi (AMF) constitute a group of root obligate biotrophs that exchange mutual benefits with about 80% of plants. They are considered natural biofertilizers, since they provide the host with water, nutrients, and pathogen protection, in exchange for photosynthetic products. Thus, AMF are primary biotic soil components which, when missing or impoverished, can lead to a less efficient ecosystem functioning. The process of re-establishing the natural level of AMF richness can represent a valid alternative to conventional fertilization practices, with a view to sustainable agriculture. The main strategy that can be adopted to achieve this goal is the direct re-introduction of AMF propagules (inoculum) into a target soil. Originally, AMF were described to generally lack host- and niche-specificity, and therefore suggested as agriculturally suitable for a wide range of plants and environmental conditions. Unfortunately, the assumptions that have been made and the results that have been obtained so far are often worlds apart. The problem is that success is unpredictable since different plant species vary their response to the same AMF species mix. Many factors can affect the success of inoculation and AMF persistence in soil, including species compatibility with the target environment, the degree of spatial competition with other soil organisms in the target niche and the timing of inoculation. Thus, it is preferable to take these factors into account when "tuning" an inoculum to a target environment in order to avoid failure of the inoculation process. Genomics and transcriptomics have led to a giant step forward in the research field of AMF, with consequent major advances in the current knowledge on the processes involved in their interaction with the host-plant and other soil organisms. The history of AMF applications in controlled and open-field conditions is now long. A review of biofertilization experiments, based on the use of AMF, has here been proposed, focusing on a few important factors that could increase the odds or jeopardize the success of the inoculation process. PMID- 26834717 TI - Out of Thin Air: Microbial Utilization of Atmospheric Gaseous Organics in the Surface Ocean. AB - Volatile and semi-volatile gas-phase organic carbon (GOC) is a largely neglected component of the global carbon cycle, with poorly resolved pools and fluxes of natural and anthropogenic GOC in the biosphere. Substantial amounts of atmospheric GOC are exchanged with the surface ocean, and subsequent utilization of specific GOC compounds by surface ocean microbial communities has been demonstrated. Yet, the final fate of the bulk of the atmospheric GOC entering the surface ocean is unknown. Our data show experimental evidence of efficient use of atmospheric GOC by marine prokaryotes at different locations in the NE Subtropical Atlantic, the Arctic Ocean and the Mediterranean Sea. We estimate that between 2 and 27% of the prokaryotic carbon demand was supported by GOC with a major fraction of GOC inputs being consumed within the mixed layer. The role of the atmosphere as a key vector of organic carbon subsidizing marine microbial metabolism is a novel link yet to be incorporated into the microbial ecology of the surface ocean as well as into the global carbon budget. PMID- 26834716 TI - Melatonin and Other Tryptophan Metabolites Produced by Yeasts: Implications in Cardiovascular and Neurodegenerative Diseases. AB - Yeast metabolism produces compounds derived from tryptophan, which are found in fermented beverages, such as wine and beer. In particular, melatonin and serotonin, may be relevant due to their bioactivity in humans. Indeed, the former is a neurohormone related to circadian rhythms, which also has a putative protective effect against degenerative diseases. Moreover, serotonin is a neurotransmitter itself, in addition to being a precursor of melatonin synthesis. This paper summarizes data reported on fermented beverages, to evaluate dietary intake. Additionally, the article reviews observed effects of yeast amino acid metabolites on the prevention of neurodegenerative diseases (Alzheimer's and Parkinson's) and angiogenesis, focusing on evidence of the molecular mechanism involved and identification of molecular targets. PMID- 26834718 TI - Spatial Interaction of Archaeal Ammonia-Oxidizers and Nitrite-Oxidizing Bacteria in an Unfertilized Grassland Soil. AB - Interrelated successive transformation steps of nitrification are performed by distinct microbial groups - the ammonia-oxidizers, comprising ammonia-oxidizing archaea (AOA) and bacteria (AOB), and nitrite-oxidizers such as Nitrobacter and Nitrospira, which are the dominant genera in the investigated soils. Hence, not only their presence and activity in the investigated habitat is required for nitrification, but also their temporal and spatial interactions. To demonstrate the interdependence of both groups and to address factors promoting putative niche differentiation within each group, temporal and spatial changes in nitrifying organisms were monitored in an unfertilized grassland site over an entire vegetation period at the plot scale of 10 m(2). Nitrifying organisms were assessed by measuring the abundance of marker genes (amoA for AOA and AOB, nxrA for Nitrobacter, 16S rRNA gene for Nitrospira) selected for the respective sub processes. A positive correlation between numerically dominant AOA and Nitrospira, and their co-occurrence at the same spatial scale in August and October, suggests that the nitrification process is predominantly performed by these groups and is restricted to a limited timeframe. Amongst nitrite-oxidizers, niche differentiation was evident in observed seasonally varying patterns of co occurrence and spatial separation. While their distributions were most likely driven by substrate concentrations, oxygen availability may also have played a role under substrate-limited conditions. Phylogenetic analysis revealed temporal shifts in Nitrospira community composition with an increasing relative abundance of OTU03 assigned to sublineage V from August onward, indicating its important role in nitrite oxidation. PMID- 26834719 TI - Hanseniaspora uvarum from Winemaking Environments Show Spatial and Temporal Genetic Clustering. AB - Hanseniaspora uvarum is one of the most abundant yeast species found on grapes and in grape must, at least before the onset of alcoholic fermentation (AF) which is usually performed by Saccharomyces species. The aim of this study was to characterize the genetic and phenotypic variability within the H. uvarum species. One hundred and fifteen strains isolated from winemaking environments in different geographical origins were analyzed using 11 microsatellite markers and a subset of 47 strains were analyzed by AFLP. H. uvarum isolates clustered mainly on the basis of their geographical localization as revealed by microsatellites. In addition, a strong clustering based on year of isolation was evidenced, indicating that the genetic diversity of H. uvarum isolates was related to both spatial and temporal variations. Conversely, clustering analysis based on AFLP data provided a different picture with groups showing no particular characteristics, but provided higher strain discrimination. This result indicated that AFLP approaches are inadequate to establish the genetic relationship between individuals, but allowed good strain discrimination. At the phenotypic level, several extracellular enzymatic activities of enological relevance (pectinase, chitinase, protease, beta-glucosidase) were measured but showed low diversity. The impact of environmental factors of enological interest (temperature, anaerobia, and copper addition) on growth was also assessed and showed poor variation. Altogether, this work provided both new analytical tool (microsatellites) and new insights into the genetic and phenotypic diversity of H. uvarum, a yeast species that has previously been identified as a potential candidate for co-inoculation in grape must, but whose intraspecific variability had never been fully assessed. PMID- 26834720 TI - Deletion of the Small RNA Chaperone Protein Hfq down Regulates Genes Related to Virulence and Confers Protection against Wild-Type Brucella Challenge in Mice. AB - Brucellosis is one of the most common zoonotic epidemics worldwide. Brucella, the etiological pathogen of brucellosis, has unique virulence characteristics, including the ability to survive within the host cell. Hfq is a bacterial chaperone protein that is involved in the survival of the pathogen under stress conditions. Moreover, hfq affects the expression of a large number of target genes. In the present study, we characterized the expression and regulatory patterns of the target genes of Hfq during brucellosis. The results revealed that hfq expression is highly induced in macrophages at the early infection stage and at the late stage of mouse infection. Several genes related to virulence, including omp25, omp31, vjbR, htrA, gntR, and dnaK, were found to be regulated by hfq during infection in BALB/c mice. Gene expression and cytokine secretion analysis revealed that an hfq-deletion mutant induced different cytokine profiles compared with that induced by 16M. Infection with the hfq-deletion mutant induced protective immune responses against 16M challenge. Together, these results suggest that hfq is induced during infection and its deletion results in significant attenuation which affects the host immune response caused by Brucella infection. By regulating genes related to virulence, hfq promotes the virulence of Brucella. The unique characteristics of the hfq-deletion mutant, including its decreased virulence and the ability to induce protective immune response upon infection, suggest that it represents an attractive candidate for the design of a live attenuated vaccine against Brucella. PMID- 26834721 TI - Novel Approaches for Fungal Transcriptomics from Host Samples. AB - Candida albicans adaptation to the host requires a profound reprogramming of the fungal transcriptome as compared to in vitro laboratory conditions. A detailed knowledge of the C. albicans transcriptome during the infection process is necessary in order to understand which of the fungal genes are important for host adaptation. Such genes could be thought of as potential targets for antifungal therapy. The acquisition of the C. albicans transcriptome is, however, technically challenging due to the low proportion of fungal RNA in host tissues. Two emerging technologies were used recently to circumvent this problem. One consists of the detection of low abundance fungal RNA using capture and reporter gene probes which is followed by emission and quantification of resulting fluorescent signals (nanoString). The other is based first on the capture of fungal RNA by short biotinylated oligonucleotide baits covering the C. albicans ORFome permitting fungal RNA purification. Next, the enriched fungal RNA is amplified and subjected to RNA sequencing (RNA-seq). Here we detail these two transcriptome approaches and discuss their advantages and limitations and future perspectives in microbial transcriptomics from host material. PMID- 26834722 TI - Phylogenetic Analyses of Shigella and Enteroinvasive Escherichia coli for the Identification of Molecular Epidemiological Markers: Whole-Genome Comparative Analysis Does Not Support Distinct Genera Designation. AB - As a leading cause of bacterial dysentery, Shigella represents a significant threat to public health and food safety. Related, but often overlooked, enteroinvasive Escherichia coli (EIEC) can also cause dysentery. Current typing methods have limited ability to identify and differentiate between these pathogens despite the need for rapid and accurate identification of pathogens for clinical treatment and outbreak response. We present a comprehensive phylogeny of Shigella and EIEC using whole genome sequencing of 169 samples, constituting unparalleled strain diversity, and observe a lack of monophyly between Shigella and EIEC and among Shigella taxonomic groups. The evolutionary relationships in the phylogeny are supported by analyses of population structure and hierarchical clustering patterns of translated gene homolog abundance. Lastly, we identified a panel of 404 single nucleotide polymorphism (SNP) markers specific to each phylogenetic cluster for more accurate identification of Shigella and EIEC. Our findings show that Shigella and EIEC are not distinct evolutionary groups within the E. coli genus and, thus, EIEC as a group is not the ancestor to Shigella. The multiple analyses presented provide evidence for reconsidering the taxonomic placement of Shigella. The SNP markers offer more discriminatory power to molecular epidemiological typing methods involving these bacterial pathogens. PMID- 26834723 TI - Revisiting the STEC Testing Approach: Using espK and espV to Make Enterohemorrhagic Escherichia coli (EHEC) Detection More Reliable in Beef. AB - Current methods for screening Enterohemorrhagic Escherichia coli (EHEC) O157 and non-O157 in beef enrichments typically rely on the molecular detection of stx, eae, and serogroup-specific wzx or wzy gene fragments. As these genetic markers can also be found in some non-EHEC strains, a number of "false positive" results are obtained. Here, we explore the suitability of five novel molecular markers, espK, espV, ureD, Z2098, and CRISPRO26:H11 as candidates for a more accurate screening of EHEC strains of greater clinical significance in industrialized countries. Of the 1739 beef enrichments tested, 180 were positive for both stx and eae genes. Ninety (50%) of these tested negative for espK, espV, ureD, and Z2098, but 12 out of these negative samples were positive for the CRISPRO26:H11 gene marker specific for a newly emerging virulent EHEC O26:H11 French clone. We show that screening for stx, eae, espK, and espV, in association with the CRISPRO26:H11 marker is a better approach to narrow down the EHEC screening step in beef enrichments. The number of potentially positive samples was reduced by 48.88% by means of this alternative strategy compared to the European and American reference methods, thus substantially improving the discriminatory power of EHEC screening systems. This approach is in line with the EFSA (European Food Safety Authority) opinion on pathogenic STEC published in 2013. PMID- 26834724 TI - Developmental Peculiarities and Seed-Borne Endophytes in Quinoa: Omnipresent, Robust Bacilli Contribute to Plant Fitness. AB - Among potential climate change-adapted crops for future agriculture, quinoa (Chenopodium quinoa), a facultative halophyte plant with exceptional nutritional properties, stands out as a prime candidate. This work examined how quinoa deals with extreme situations during seed rehydration. Quinoa distinguishes itself from other plants in multiple ways. It germinates within minutes, even under extremely hostile conditions. Broken seeds/split embryos are able to regenerate. Furthermore, quinoa seedlings are resurrection-competent. These peculiarities became in part explainable upon discovery of seed-borne microorganisms. 100% of quinoa seeds, from different sources, are inhabited by diverse members of the genus Bacillus. These endophytes are motile and reside in all seedling organs, indicating vertical transmission. Owing to their high catalase activities and superoxide contents the bacteria potentially manipulate the host's redox status. Superoxide-driven cell expansion enables quinoa to overcome a critical period in development, seedling establishment. Quinoa's immediate confrontation with "foreign" reactive oxygen species and bacterial elicitors likely induces a naturally primed state, enabling plants to withstand extreme situations. The endophytic bacteria, which are cultivable and highly robust themselves, have high potential for application in agriculture, food (amylase) and cosmetics (catalase) industry. This work also discusses the potential of transferring quinoa's microbiome to improve stress resistance in other plant species. PMID- 26834725 TI - Microbial Profiling of a Suppressiveness-Induced Agricultural Soil Amended with Composted Almond Shells. AB - This study focused on the microbial profile present in an agricultural soil that becomes suppressive after the application of composted almond shells (AS) as organic amendments. For this purpose, we analyzed the functions and composition of the complex communities present in an experimental orchard of 40-year-old avocado trees, many of them historically amended with composted almond shells. The role of microbes in the suppression of Rosellinia necatrix, the causative agent of avocado white root rot, was determined after heat-treatment and complementation experiments with different types of soil. Bacterial and fungal profiles obtained from natural soil samples based on the 16S rRNA gene and ITS sequencing revealed slight differences among the amended (AS) and unamended (CT) soils. When the soil was under the influence of composted almond shells as organic amendments, an increase in Proteobacteria and Ascomycota groups was observed, as well as a reduction in Acidobacteria and Mortierellales. Complementary to these findings, functional analysis by GeoChip 4.6 confirmed these subtle differences, mainly present in the relative abundance of genes involved in the carbon cycle. Interestingly, a group of specific probes included in the "soil benefit" category was present only in AS-amended soils, corresponding to specific microorganisms previously described as potential biocontrol agents, such as Pseudomonas spp., Burkholderia spp., or Actinobacteria. Considering the results of both analyses, we determined that AS amendments to the soil led to an increase in some orders of Gammaproteobacteria, Betaproteobacteria, and Dothideomycetes, as well as a reduction in the abundance of Xylariales fungi (where R. necatrix is allocated). The combination of microbial action and substrate properties of suppressiveness are discussed. PMID- 26834726 TI - Novel Virophages Discovered in a Freshwater Lake in China. AB - Virophages are small double-stranded DNA viruses that are parasites of giant DNA viruses that infect unicellular eukaryotes. Here we identify a novel group of virophages, named Dishui Lake virophages (DSLVs) that were discovered in Dishui Lake (DSL): an artificial freshwater lake in Shanghai, China. Based on PCR and metagenomic analysis, the complete genome of DSLV1 was found to be circular and 28,788 base pairs in length, with a G+C content 43.2%, and 28 predicted open reading frames (ORFs). Fifteen of the DSLV1 ORFs have sequence similarity to known virophages. Two DSLV1 ORFs exhibited sequence similarity to that of prasinoviruses (Phycodnaviridae) and chloroviruses (Phycodnaviridae), respectively, suggesting horizontal gene transfer occurred between these large algal DNA viruses and DSLV1. 46 other virophages-related contigs were also obtained, including six homologous major capsid protein (MCP) gene. Phylogenetic analysis of these MCPs showed that DSLVs are closely related to OLV (Organic Lake virophage) and YSLVs (Yellowstone Lake virophages), especially to YSLV3, except for YSLV7. These results indicate that freshwater ecotopes are the hotbed for discovering novel virophages as well as understanding their diversity and properties. PMID- 26834727 TI - Biosurfactant Produced by Salmonella Enteritidis SE86 Can Increase Adherence and Resistance to Sanitizers on Lettuce Leaves (Lactuca sativa L., cichoraceae). AB - Salmonella Enteritidis SE86 is an important foodborne pathogen in Southern Brazil and it is able to produce a biosurfactant. However, the importance of this compound for the microorganism is still unknown. This study aimed to investigate the influence of the biosurfactant produced by S. Enteritidis SE86 on adherence to slices of lettuce leaves and on resistance to sanitizers. First, lettuce leaves were inoculated with S. Enteritidis SE86 in order to determine the amount of biosurfactant produced. Subsequently, lettuce leaves were inoculated with S. Enteritidis SE86 with and without the biosurfactant, and the adherence and bacterial resistance to different sanitization methods were evaluated. S. Enteritidis SE86 produced biosurfactant after 16 h (emulsification index of 11 to 52.15 percent, P < 0.05) and showed greater adherence capability and resistance to sanitization methods when the compound was present. The scanning electron microscopy demonstrated that S. Enteritidis was able to adhere, form lumps, and invade the lettuce leaves' stomata in the presence of the biosurfactant. Results indicated that the biosurfactant produced by S. Enteritidis SE86 contributed to adherence and increased resistance to sanitizers when the microorganism was present on lettuce leaves. PMID- 26834729 TI - The Role of DNA Restriction-Modification Systems in the Biology of Bacillus anthracis. AB - Restriction-modification (R-M) systems are widespread among prokaryotes and, depending on their type, may be viewed as selfish genetic elements that persist as toxin-antitoxin modules, or as cellular defense systems against phage infection that confer a selective advantage to the host bacterium. Studies in the last decade have made it amply clear that these two options do not exhaust the list of possible biological roles for R-M systems. Their presence in a cell may also have a bearing on other processes such as horizontal gene transfer and gene regulation. From genome sequencing and experimental data, we know that Bacillus anthracis encodes at least three methylation-dependent (typeIV) restriction endonucleases (RE), and an orphan DNA methyltransferase. In this article, we first present an outline of our current knowledge of R-M systems in B. anthracis. Based on available DNA sequence data, and on our current understanding of the functions of similar genes in other systems, we conclude with hypotheses on the possible roles of the three REs and the orphan DNA methyltransferase. PMID- 26834728 TI - Therapeutic Application of Synbiotics, a Fusion of Probiotics and Prebiotics, and Biogenics as a New Concept for Oral Candida Infections: A Mini Review. AB - Candida is a major human fungal pathogen causing infectious conditions predominantly in the elderly and immunocompromised hosts. Although Candida resides as a member of the oral indigenous microbiota in symbiosis, some circumstances may cause microbial imbalance leading to dysbiosis and resultant oral candidiasis. Therefore, oral microbial symbiosis that suppresses the overgrowth of Candida is important for a healthy oral ecosystem. In this regard, probiotics, prebiotics, and synbiotics can be considered a potential therapeutic and preventive strategy against oral candidiasis. Prebiotics have a direct effect on microbial growth as they stimulate the growth of beneficial bacteria and suppress the growth of pathogens. Probiotics render a local protective effect against pathogens and a systemic indirect effect on immunological amelioration. Synbiotics are fusion products of prebiotics and probiotics. This mini review discusses the potential use and associated limitations of probiotics, prebiotics, and synbiotics for the prevention and treatment of oral candidiasis. We will also introduce biogenics, a recent concept derived from the work on probiotics. Biogenics advocates the use of beneficial bioactive substances produced by probiotic bacteria, whose activities are independent from the viability of probiotic bacteria in human bodies. PMID- 26834730 TI - Unraveling the Enzymatic Basis of Wine "Flavorome": A Phylo-Functional Study of Wine Related Yeast Species. AB - Non-Saccharomyces yeasts are a heterogeneous microbial group involved in the early stages of wine fermentation. The high enzymatic potential of these yeasts makes them a useful tool for increasing the final organoleptic characteristics of wines in spite of their low fermentative power. Their physiology and contribution to wine quality are still poorly understood, with most current knowledge being acquired empirically and in most cases based in single species and strains. This work analyzed the metabolic potential of 770 yeast isolates from different enological origins and representing 15 different species, by studying their production of enzymes of enological interest and linking phylogenetic and enzymatic data. The isolates were screened for glycosidase enzymes related to terpene aroma release, the beta-lyase activity responsible for the release of volatile thiols, and sulfite reductase. Apart from these aroma-related activities, protease, polygalacturonase and cellulase activities were also studied in the entire yeast collection, being related to the improvement of different technological and sensorial features of wines. In this context, and in terms of abundance, two different groups were established, with alpha-L arabinofuranosidase, polygalacturonase and cellulase being the less abundant activities. By contrast, beta-glucosidase and protease activities were widespread in the yeast collection studied. A classical phylogenetic study involving the partial sequencing of 26S rDNA was conducted in conjunction with the enzymatic profiles of the 770 yeast isolates for further typing, complementing the phylogenetic relationships established by using 26S rDNA. This has rendered it possible to foresee the contribution different yeast species make to wine quality and their potential applicability as pure inocula, establishing species-specific behavior. These consistent results allowed us to design future targeted studies on the impact different non-Saccharomyces yeast species have on wine quality, understanding intra and interspecific enzymatic odds and, therefore, aiming to predict the most suitable application for the current non-Saccharomyces strains, as well as the potential future applications of new strains. This work therefore contributes to a better understanding of the concept of wine microbiome and its potential consequences for wine quality, as well as to the knowledge of non Saccharomyces yeasts for their use in the wine industry. PMID- 26834732 TI - Vaccines Directed Against Microorganisms or Their Products Present During Biofilm Lifestyle: Can We Make a Translation as a Broad Biological Model to Tuberculosis? AB - Tuberculosis (TB) remains as a global public health problem. In recent years, experimental evidence suggesting the relevance of in vitro pellicle (a type of biofilm formed at the air-liquid interface) production as a phenotype mimicking aspects found by Mycobacterium tuberculosis-complex bacteria during in vivo infection has started to accumulate. There are still opportunities for better diagnostic tools, therapeutic molecules as well as new vaccine candidates to assist in TB control programs worldwide and particularly in less developed nations. Regarding vaccines, despite the availability of a live, attenuated strain (Mycobacterium bovis BCG) since almost a century ago, its variable efficacy and lack of protection against pulmonary and latent disease has prompted basic and applied research leading to preclinical and clinical evaluation of up to 15 new candidates. In this work, I present examples of vaccines based on whole cells grown as biofilms, or specific proteins expressed under such condition, and the effect they have shown in relevant animal models or directly in the natural host. I also discuss why it might be worthwhile to explore these approaches, for constructing and developing new vaccine candidates for testing their efficacy against TB. PMID- 26834733 TI - A Chlorhexidine- Agar Plate Culture Medium Protocol to Complement Standard Broth Culture of Mycobacterium tuberculosis. AB - The culture of Mycobacterium tuberculosis using parallel inoculation of a solid culture medium and a liquid broth provides the gold standard for the diagnosis of tuberculosis. Here, we evaluated a chlorhexidine decontamination-MOD9 solid medium protocol versus the standard NALC-NaOH-Bactec 960 MGIT protocol for the diagnosis of pulmonary tuberculosis by culture. Three-hundred clinical specimens comprising 193 sputa, 30 bronchial aspirates, 10 broncho-alveolar lavages, 47 stools, and 20 urines were prospectively submitted for the routine diagnosis of tuberculosis. The contamination rates were 5/300 (1.7%) using the MOD9 protocol and 17/300 (5.7%) with the Bactec protocol, respectively (P < 0.05, Fisher exact test). Of a total of 50 Mycobacterium isolates (48 M. tuberculosis and two Mycobacterium abscessus) were cultured. Out of these 50, 48 (96%) isolates were found using the MOD9 protocol versus 35 (70%) when using the Bactec protocol (P < 0.05, Fisher exact test). The time to positivity was 10.1 +/- 3.9 days versus 14.7 +/- 7.3 days, respectively, (P < 0.05, Student's t-test). These data confirmed the usefulness of parallel inoculation of a solid culture medium with broth for the recovery of M. tuberculosis in agreement with current recommendations. More specifically, chlorhexidine decontamination and inoculation of the MOD9 solid medium could be proposed to complement the standard Bactec 960 MGIT broth protocol. PMID- 26834731 TI - Phenotypic Modifications in Staphylococcus aureus Cells Exposed to High Concentrations of Vancomycin and Teicoplanin. AB - Bacterial cells are known to change the fatty acid (FA) composition of the phospholipids as a phenotypic response to environmental conditions and to the presence of toxic compounds such as antibiotics. In the present study, Staphylococcus aureus cells collected during the exponential growth phase were challenged with 50 and 100 mg/L of vancomycin and teicoplanin, which are concentrations high enough to kill the large majority of the cell population. Colony-forming unit counts showed biphasic killing kinetics, typical for persister cell enrichment, in both antibiotics and concentrations tested. However, fluorescence microscopy showed the existence of viable but non culturable (VBNC) cells in a larger number than that of possible persister cells. The analysis of the FA composition of the cells showed that, following antibiotic exposure up to 6 h, the survivor cells have an increased percentage of saturated FAs, a significant reduced percentage of branched FAs and an increased iso/anteiso branched FA ratio when compared to cells exhibiting a regular phenotype. This should result in lower membrane fluidity. However, cells exposed for 8-24 h presented an increased branched/saturated and lower iso/anteiso branched FA ratios, and thus increased membrane fluidity. Furthermore, the phenotypic changes were transmitted to daughter cells grown in drug-free media. The fact that VBNC cells presented nearly the same FA composition as those obtained after cell growth in drug-free media, which could only be the result of growth of persister cells, suggest that VBNC and persister phenotypes share the same type of response to antibiotics at the lipid level. PMID- 26834734 TI - Receptor-Interacting Protein Kinase-2 Inhibition by CYLD Impairs Antibacterial Immune Responses in Macrophages. AB - Upon infection with intracellular bacteria, nucleotide oligomerization domain protein 2 recognizes bacterial muramyl dipeptide and binds, subsequently, to receptor-interacting serine/threonine kinase 2 (RIPK2), which activates immune responses via the nuclear factor kappa-light-chain enhancer of activated B cells (NF-kappaB) and extracellular signal-regulated kinase (ERK) pathways. Activation of RIPK2 depends on its K63 ubiquitination by E3 ligases, whereas the deubiquitinating enzyme A20 counter regulates RIPK2 activity by cleaving K63 polyubiquitin chains from RIPK2. Here, we newly identify the deubiquitinating enzyme CYLD as a new inhibitor of RIPK2. We show that CYLD binds to and removes K63-polyubiquitin chains from RIPK2 in Listeria monocytogenes (Lm) infected murine bone marrow-derived macrophages. CYLD-mediated K63 deubiquitination of RIPK2 resulted in an impaired activation of both NF-kappaB and ERK1/2 pathways, reduced production of proinflammatory cytokines interleukin-6 (IL-6), IL-12, anti listerial reactive oxygen species (ROS) and nitric oxide (NO), and, finally, impaired pathogen control. In turn, RIPK2 inhibition by siRNA prevented activation of NF-kappaB and ERK1/2 and completely abolished the protective effect of CYLD deficiency with respect to the production of IL-6, NO, ROS, and pathogen control. Noteworthy, CYLD also inhibited autophagy of Listeria in a RIPK2-ERK1/2 dependent manner. The protective function of CYLD deficiency was dependent on interferon gamma (IFN-gamma) prestimulation of infected macrophages. Interestingly, the reduced NF-kappaB activation in CYLD-expressing macrophages limited the protective effect of IFN-gamma by reducing NF-kappaB-dependent signal transducers and activators of transcription-1 (STAT1) activation. Taken together, our study identifies CYLD as an important inhibitor of RIPK2-dependent antibacterial immune responses in macrophages. PMID- 26834736 TI - Adipose Mesenchymal Stem Cells Isolated after Manual or Water-jet-Assisted Liposuction Display Similar Properties. AB - Mesenchymal stem or stromal cells (MSC) are under investigation in many clinical trials for their therapeutic potential in a variety of diseases, including autoimmune and inflammatory disorders. One of the main sources of MSCs is the adipose tissue, which is mainly obtained by manual liposuction using a cannula linked to a syringe. However, in the past years, a number of devices for fat liposuction intended for clinical use have been commercialized but few papers have compared these procedures in terms of stromal vascular fraction (SVF) or adipose mesenchymal stromal cells (ASC). The objective of the present study was to compare and qualify for clinical use the ASC obtained from fat isolated with the manual or the Bodyjet((r)) water-jet-assisted procedure. Although the initial number of cells obtained after collagenase digestion was higher with the manual procedure, the percentage of dead cells, the number of colony forming unit fibroblast and the phenotype of cells were identical in the SVF at isolation (day 0) and in the ASC populations at day 14. We also showed that the osteogenic and adipogenic differentiation potentials of ASCs were identical between preparations while a slight but significant higher in vitro immunosuppressive effect was observed with ASCs isolated from fat removed with a cannula. The difference in the immunomodulatory effect between ASC populations was, however, not observed in vivo using the delayed-type hypersensitivity (DTH) model. Our data, therefore, indicate that the procedure for fat liposuction does not impact the characteristics or the therapeutic function of ASCs. PMID- 26834735 TI - Inducing and Administering Tregs to Treat Human Disease. AB - Regulatory T cells (Tregs) control unwanted immune responses, including those that mediate tolerance to self as well as to foreign antigens. Their mechanisms of action include direct and indirect effects on effector T cells and important functions in tissue repair and homeostasis. Tregs express a number of cell surface markers and transcriptional factors that have been instrumental in defining their origins and potentially their function. A number of immune therapies, such as rapamycin, IL-2, and anti-T cell antibodies, are able to induce Tregs and are being tested for their efficacy in diverse clinical settings with exciting preliminary results. However, a balance exists with the use of some, such as IL-2, that may have effects on unwanted populations as well as promoting expansion and survival of Tregs requiring careful selection of dose for clinical use. The use of cell surface markers has enabled investigators to isolate and expand ex vivo Tregs more than 500-fold routinely. Clinical trials have begun, administering these expanded Tregs to patients as a means of suppressing autoimmune and alloimmune responses and potentially inducing immune tolerance. Studies in the future are likely to build on these initial technical achievements and use combinations of agents to improve the survival and functional capacity of Tregs. PMID- 26834738 TI - Epigenetic Modulators of Monocytic Function: Implication for Steady State and Disease in the CNS. AB - Epigenetic alterations are necessary for the establishment of functional and phenotypic diversity in the populations of immune cells of the monocytic lineage. The epigenetic status of individual genes at different time points defines their transcriptional responses throughout development and in response to environmental stimuli. Epigenetic states are defined at the level of DNA modifications, chromatin modifications, as well as at the level of RNA base changes through RNA editing. Drawing from lessons regarding the epigenome and epitranscriptome of cells of the monocytic lineage in the periphery, and from recently published RNAseq data deriving from brain-resident monocytes, we discuss the impact of modulation of these epigenetic states and how they affect processes important for the development of a healthy brain, as well as mechanisms of neurodegenerative disease and aging. An understanding of the varied brain responses and pathologies in light of these novel gene regulatory systems in monocytes will lead to important new insights in the understanding of the aging process and the treatment and diagnosis of neurodegenerative disease. PMID- 26834737 TI - Evasion of the Immune Response by Trypanosoma cruzi during Acute Infection. AB - Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical disease that affects millions of people mainly in Latin America. To establish a life-long infection, T. cruzi must subvert the vertebrate host's immune system, using strategies that can be traced to the parasite's life cycle. Once inside the vertebrate host, metacyclic trypomastigotes rapidly invade a wide variety of nucleated host cells in a membrane-bound compartment known as the parasitophorous vacuole, which fuses to lysosomes, originating the phagolysosome. In this compartment, the parasite relies on a complex network of antioxidant enzymes to shield itself from lysosomal oxygen and nitrogen reactive species. Lysosomal acidification of the parasitophorous vacuole is an important factor that allows trypomastigote escape from the extremely oxidative environment of the phagolysosome to the cytoplasm, where it differentiates into amastigote forms. In the cytosol of infected macrophages, oxidative stress instead of being detrimental to the parasite, favors amastigote burden, which then differentiates into bloodstream trypomastigotes. Trypomastigotes released in the bloodstream upon the rupture of the host cell membrane express surface molecules, such as calreticulin and GP160 proteins, which disrupt initial and key components of the complement pathway, while others such as glycosylphosphatidylinositol-mucins stimulate immunoregulatory receptors, delaying the progression of a protective immune response. After an immunologically silent entry at the early phase of infection, T. cruzi elicits polyclonal B cell activation, hypergammaglobulinemia, and unspecific anti-T. cruzi antibodies, which are inefficient in controlling the infection. Additionally, the coexpression of several related, but not identical, epitopes derived from trypomastigote surface proteins delays the generation of T. cruzi-specific neutralizing antibodies. Later in the infection, the establishment of an anti-T. cruzi CD8(+) immune response focused on the parasite's immunodominant epitopes controls parasitemia and tissue infection, but fails to completely eliminate the parasite. This outcome is not detrimental to the parasite, as it reduces host mortality and maintains the parasite infectivity toward the insect vectors. PMID- 26834739 TI - IL-22-Expressing Murine Lymphocytes Display Plasticity and Pathogenicity in Reporter Mice. AB - IL-22 has multiple activities ranging from tissue repair to inflammation. To characterize the pathogenicity and plasticity of cells that produce IL-22, a novel reporter mouse strain was generated. Homeostatic IL-22 reporter expression was observed in intestinal lymphoid cells identified as CD4 T cells and ILC3 cells. In a model of inflammatory bowel disease, CD4 T cells strongly expressed the IL-22 reporter in mesenteric lymph node. To examine plasticity of IL-22(+) T cells, they were purified after generation in vitro or in vivo from inflamed colon, and then cultured under Th1, Th2, or Th17 conditions. In vitro-generated IL-22(+) CD4 T cells showed relatively durable IL-22 expression under Th1 or Th2 conditions, whereas in vivo-generated cells rapidly lost IL-22 expression under these conditions. In vitro-generated cells could not be diverted to express Th1 or Th2 cytokines despite the expression of "master regulators." In vivo-generated cells could be diverted, at very low frequency, to express Th1 or Th2 cytokines. Both in vitro- and in vivo-generated cells could be induced in vitro to express high levels of IL-17A and IL-17F, assigning them to a "Th17 biased" class. However, IL-27 potently downregulated IL-22 expression. To examine IL-22(+) T cell pathogenicity, in vitro-generated cells were transferred into Rag1(-/-) mice, retaining the modest reporter expression and inducing moderate colitis. In contrast, IL-22 expressers from colitic mice, transferred into secondary hosts, lost reporter expression, acquired high T-bet and modest IFNgamma and IL-17 expression, and induced severe colitis. These findings are consistent with a model of strong polarization under optimal in vitro conditions, but a plastic state of T cells in vivo. PMID- 26834741 TI - Editorial: Innate Immune Cell Determinants of T Cell Immunity: From Basic Mechanisms to Clinical Implications. PMID- 26834743 TI - Murine Butyrophilin-Like 1 and Btnl6 Form Heteromeric Complexes in Small Intestinal Epithelial Cells and Promote Proliferation of Local T Lymphocytes. AB - To date, few molecular conduits mediating the cross-talk between intestinal epithelial cells and intraepithelial lymphocytes (IELs) have been described. We recently showed that butyrophilin-like (Btnl) 1 can attenuate the epithelial response to activated IELs, resulting in reduced production of proinflammatory mediators, such as IL-6 and CXCL1. We here report that like Btnl1, murine Btnl6 expression is primarily confined to the intestinal epithelium. Although Btnl1 can exist in a cell surface-expressed homomeric form, we found that it additionally forms heteromeric complexes with Btnl6, and that the engagement of Btnl1 is a prerequisite for surface expression of Btnl6 on intestinal epithelial cells. In an IEL-epithelial cell coculture system, enforced epithelial cell expression of Btnl1 significantly enhanced the proliferation of IELs in the absence of exogenous activation. The effect on proliferation was dependent on the presence of IL-2 or IL-15 and restricted to IELs upregulating CD25. In the gammadelta T cell subset, the Btnl1-Btnl6 complex, but not Btnl1, specifically elevated the proliferation of IELs bearing the Vgamma7Vdelta4 receptor. Thus, our results show that murine epithelial cell-specific Btnl proteins can form intrafamily heterocomplexes and suggest that the interaction between Btnl proteins and IELs regulates the expansion of IELs in the intestinal mucosa. PMID- 26834740 TI - Exploiting the Immunogenic Potential of Cancer Cells for Improved Dendritic Cell Vaccines. AB - Cancer immunotherapy is currently the hottest topic in the oncology field, owing predominantly to the discovery of immune checkpoint blockers. These promising antibodies and their attractive combinatorial features have initiated the revival of other effective immunotherapies, such as dendritic cell (DC) vaccinations. Although DC-based immunotherapy can induce objective clinical and immunological responses in several tumor types, the immunogenic potential of this monotherapy is still considered suboptimal. Hence, focus should be directed on potentiating its immunogenicity by making step-by-step protocol innovations to obtain next generation Th1-driving DC vaccines. We review some of the latest developments in the DC vaccination field, with a special emphasis on strategies that are applied to obtain a highly immunogenic tumor cell cargo to load and to activate the DCs. To this end, we discuss the effects of three immunogenic treatment modalities (ultraviolet light, oxidizing treatments, and heat shock) and five potent inducers of immunogenic cell death [radiotherapy, shikonin, high-hydrostatic pressure, oncolytic viruses, and (hypericin-based) photodynamic therapy] on DC biology and their application in DC-based immunotherapy in preclinical as well as clinical settings. PMID- 26834744 TI - Induction of Monocyte Chemoattractant Proteins in Macrophages via the Production of Granulocyte/Macrophage Colony-Stimulating Factor by Breast Cancer Cells. AB - Monocyte chemoattractant protein-1 (MCP-1)/CCL2 plays an important role in the initiation and progression of cancer. We previously reported that in 4T1 murine breast cancer, non-tumor stromal cells, including macrophages, were the major source of MCP-1. In the present study, we analyzed the potential mechanisms by which MCP-1 is upregulated in macrophages infiltrating 4T1 tumors. We found that cell-free culture supernatants of 4T1 cells (4T1-sup) markedly upregulated MCP-1 production by peritoneal inflammatory macrophages. 4T1-sup also upregulated other MCPs, such as MCP-3/CCL7 and MCP-5/CCL12, but modestly upregulated neutrophil chemotactic chemokines, such as KC/CXCL1 or MIP-2/CXCL2. Physicochemical analysis indicated that an approximately 20-30 kDa 4T1 cell product was responsible for the capacity of 4T1-sup to upregulate MCP-1 expression by macrophages. A neutralizing antibody against granulocyte/macrophage colony-stimulating factor (GM-CSF), but not macrophage CSF, almost completely abrogated MCP-1-inducing activity of 4T1-sup, and recombinant GM-CSF potently upregulated MCP-1 production by macrophages. The expression levels of GM-CSF in 4T1 tumors in vivo were higher than other tumors, such as Lewis lung carcinoma. Treatment of mice with anti-GM CSF antibody significantly reduced the growth of 4T1 tumors at the injection sites but did not reduce MCP-1 production or lung metastasis in tumor-bearing mice. These results indicate that 4T1 cells have the capacity to directly upregulate MCP-1 production by macrophages by releasing GM-CSF; however, other mechanisms are also involved in increased MCP-1 levels in the 4T1 tumor microenvironment. PMID- 26834742 TI - Role of HLA Adaptation in HIV Evolution. AB - Killing of HIV-infected cells by CD8(+) T-cells imposes strong selection pressure on the virus toward escape. The HLA class I molecules that are successful in mediating some degree of control over the virus are those that tend to present epitopes in conserved regions of the proteome, such as in p24 Gag, in which escape also comes at a significant cost to viral replicative capacity (VRC). In some instances, compensatory mutations can fully correct for the fitness cost of such an escape variant; in others, correction is only partial. The consequences of these events within the HIV-infected host, and at the population level following transmission of escape variants, are discussed. The accumulation of escape mutants in populations over the course of the epidemic already shows instances of protective HLA molecules losing their impact, and in certain cases, a modest decline in HIV virulence in association with population-level increase in mutants that reduce VRC. PMID- 26834745 TI - Aeroparticles, Composition, and Lung Diseases. AB - Urban air pollution is a serious worldwide problem due to its impact on human health. In the past 60 years, growing evidence established a correlation between exposure to air pollutants and the developing of severe respiratory diseases. Recently particulate matter (PM) is drawing more public attention to various aspects including historical backgrounds, physicochemical characteristics, and its pathological role. Therefore, this review is focused on these aspects. The most famous air pollution disaster happened in London on December 1952; it has been calculated that more than 4,000 deaths occurred during this event. Air pollution is a complex mix of gases and particles. Gaseous pollutants disseminate deeply into the alveoli, allowing its diffusion through the blood-air barrier to several organs. Meanwhile, PM is a mix of solid or liquid particles suspended in the air. PM is deposited at different levels of the respiratory tract, depending on its size: coarse particles (PM10) in upper airways and fine particles (PM2.5) can be accumulated in the lung parenchyma, inducing several respiratory diseases. Additionally to size, the composition of PM has been associated with different toxicological outcomes on clinical and epidemiological, as well as in vivo and in vitro animal and human studies. PM can be constituted by organic, inorganic, and biological compounds. All these compounds are capable of modifying several biological activities, including alterations in cytokine production, coagulation factors balance, pulmonary function, respiratory symptoms, and cardiac function. It can also generate different modifications during its passage through the airways, like inflammatory cells recruitment, with the release of cytokines and reactive oxygen species (ROS). These inflammatory mediators can activate different pathways, such as MAP kinases, NF-kappaB, and Stat-1, or induce DNA adducts. All these alterations can mediate obstructive or restrictive respiratory diseases like asthma, COPD, pulmonary fibrosis, and even cancer. In 2013, outdoor air pollution was classified as Group 1 by IARC based on all research studies data about air pollution effects. Therefore, it is important to understand how PM composition can generate several pulmonary pathologies. PMID- 26834748 TI - Editorial: Memory T Cells: Effectors, Regulators, and Implications for Transplant Tolerance. PMID- 26834746 TI - Responses to Microbial Challenges by SLAMF Receptors. AB - The SLAMF family (SLAMF) of cell surface glycoproteins is comprised of nine glycoproteins and while SLAMF1, 3, 5, 6, 7, 8, and 9 are self-ligand receptors, SLAMF2 and SLAMF4 interact with each other. Their interactions induce signal transduction networks in trans, thereby shaping immune cell-cell communications. Collectively, these receptors modulate a wide range of functions, such as myeloid cell and lymphocyte development, and T and B cell responses to microbes and parasites. In addition, several SLAMF receptors serve as microbial sensors, which either positively or negatively modulate the function of macrophages, dendritic cells, neutrophils, and NK cells in response to microbial challenges. The SLAMF receptor-microbe interactions contribute both to intracellular microbicidal activity as well as to migration of phagocytes to the site of inflammation. In this review, we describe the current knowledge on how the SLAMF receptors and their specific adapters SLAM-associated protein and EAT-2 regulate innate and adaptive immune responses to microbes. PMID- 26834747 TI - TCR Signal Strength Alters T-DC Activation and Interaction Times and Directs the Outcome of Differentiation. AB - The ability of CD4+ T cells to differentiate into effector subsets underpins their ability to shape the immune response and mediate host protection. During T cell receptor-induced activation of CD4+ T cells, both the quality and quantity of specific activatory peptide/MHC ligands have been shown to control the polarization of naive CD4+ T cells in addition to co-stimulatory and cytokine based signals. Recently, advances in two--photon microscopy and tetramer-based cell tracking methods have allowed investigators to greatly extend the study of the role of TCR signaling in effector differentiation under in vivo conditions. In this review, we consider data from recent in vivo studies analyzing the role of TCR signal strength in controlling the outcome of CD4+ T cell differentiation and discuss the role of TCR in controlling the critical nature of CD4+ T cell interactions with dendritic cells during activation. We further propose a model whereby TCR signal strength controls the temporal aspects of T-DC interactions and the implications for this in mediating the downstream signaling events, which influence the transcriptional and epigenetic regulation of effector differentiation. PMID- 26834749 TI - Tolerogenic IDO(+) Dendritic Cells Are Induced by PD-1-Expressing Mast Cells. AB - Mast cells (MCs) are tissue resident cells, rich in inflammatory mediators, involved in allergic reactions, and with an increasingly recognized role in immunomodulation. Dendritic cells (DCs), on the other hand, are central to the determination of immune response patterns, being highly efficient antigen presenting cells that respond promptly to changes in their microenvironment. Here, we show that direct cell contact between immature monocyte-derived DCs (iDCs) and MC bends DCs toward tolerance induction. DCs that had direct contact with MC (MC-iDC) decreased HLA-DR but increased PD-L1 expression and stimulated regulatory T lymphocytes, which expresses FoxP3(+), secrete TGF-beta and IL-10, and suppress the proliferation of mitogen-stimulated naive T lymphocytes. Furthermore, MC-iDC expressed higher levels of indoleamine-2,3-deoxigenase (IDO), a phenomenon that was blocked by treatment of MC with anti-PD-1 or by the treatment of DCs with anti-PD-L1 or anti-PD-L2, but not by blocking of H1 and H2 histamine receptors on DCs. Contact with MC also increased phosphorylated STAT-3 levels in iDCs. When a STAT-3 inhibitor, JSI-124, was added to the DCs before contact with MC, the MC-iDC recovered their ability to induce allogeneic T cell proliferation and did not increase their IDO expression. PMID- 26834750 TI - The Role of CD4 T Cell Memory in Generating Protective Immunity to Novel and Potentially Pandemic Strains of Influenza. AB - Recent events have made it clear that potentially pandemic strains of influenza regularly pose a threat to human populations. Therefore, it is essential that we develop better strategies to enhance vaccine design and evaluation to predict those that will be poor responders to vaccination and to identify those that are at particular risk of disease-associated complications following infection. Animal models have revealed the discrete functions that CD4 T cells play in developing immune response and to influenza immunity. However, humans have a complex immunological history with influenza through periodic infection and vaccination with seasonal variants, leading to the establishment of heterogeneous memory populations of CD4 T cells that participate in subsequent responses. The continual evolution of the influenza-specific CD4 T cell repertoire involves both specificity and function and overlays other restrictions on CD4 T cell activity derived from viral antigen handling and MHC class II:peptide epitope display. Together, these complexities in the influenza-specific CD4 T cell repertoire constitute a formidable obstacle to predicting protective immune response to potentially pandemic strains of influenza and in devising optimal vaccine strategies to potentiate these responses. We suggest that more precise efforts to identify and enumerate both the positive and negative contributors within the CD4 T cell compartment will aid significantly in the achievement of these goals. PMID- 26834751 TI - Tregalizumab - A Monoclonal Antibody to Target Regulatory T Cells. AB - Regulatory T cells (Tregs) represent a subpopulation of CD4(+) T cells, which are essential for the maintenance of immunological tolerance. The absence or dysfunction of Tregs can lead to autoimmunity and allergies. The restoration of functional Tregs and/or Treg cell numbers represents a novel and attractive approach for the treatment of autoimmune diseases, e.g., rheumatoid arthritis (RA). The CD4 cell surface receptor is a target for modulation of T cell function. Monoclonal antibodies (mAbs) against CD4 have previously been tested for the treatment of autoimmune diseases, including RA. Furthermore, in model systems, anti-CD4 antibodies are able to induce tolerance and mediate immunomodulatory effects through a variety of mechanisms. Despite the availability of innovative and effective therapies for RA, many patients still have persistently active disease or experience adverse events that can limit use. A growing body of evidence suggests that Treg modulation could offer a new therapeutic strategy in RA and other autoimmune disorders. Here, we describe tregalizumab (BT-061), which is a novel, non-depleting IgG1 mAb that binds to a unique epitope of CD4. Tregalizumab represents the first humanized anti-CD4 mAb that selectively induces Treg activation. PMID- 26834753 TI - Expression of Mouse MGAT in Arabidopsis Results in Increased Lipid Accumulation in Seeds. AB - Worldwide demand for vegetable oil is projected to double within the next 30 years due to increasing food, fuel, and industrial requirements. There is therefore great interest in metabolic engineering strategies that boost oil accumulation in plant tissues, however, efforts to date have only achieved levels of storage lipid accumulation in plant tissues far below the benchmark to meet demand. Monoacylglycerol acyltransferase (MGAT) is predominantly associated with lipid absorption and resynthesis in the animal intestine where it catalyzes monoacylglycerol (MAG) to form diacylglycerol (DAG), and then triacylglycerol (TAG). In contrast plant lipid biosynthesis routes do not include MGAT. Rather, DAG and TAG are either synthesized from glycerol-3-phosphate by a series of three subsequent acylation reactions, or originated from phospholipids via an acyl editing pathway. Mouse MGATs 1 and 2 have been shown to increase oil content transiently in Nicotiana benthamiana leaf tissue by 2.6 fold. Here we explore the feasibility of this approach to increase TAG in Arabidopsis thaliana seed. The stable MGAT2 expression resulted in a significant increase in seed oil content by 1.32 fold. We also report evidence of the MGAT2 activity based on in vitro assays. Up to 3.9 fold increase of radiolabeled DAG were produced in seed lysate which suggest that the transgenic MGAT activity can result in DAG re-synthesis by salvaging the MAG product of lipid breakdown. The expression of MGAT2 therefore creates an independent and complementary TAG biosynthesis route to the endogenous Kennedy pathway and other glycerolipid synthesis routes. PMID- 26834752 TI - Ethylene, a Hormone at the Center-Stage of Nodulation. AB - Nodulation is the result of a beneficial interaction between legumes and rhizobia. It is a sophisticated process leading to nutrient exchange between the two types of symbionts. In this association, within a nodule, the rhizobia, using energy provided as photosynthates, fix atmospheric nitrogen and convert it to ammonium which is available to the plant. Nodulation is recognized as an essential process in nitrogen cycling and legume crops are known to enrich agricultural soils in nitrogenous compounds. Furthermore, as they are rich in nitrogen, legumes are considered important as staple foods for humans and fodder for animals. To tightly control this association and keep it mutualistic, the plant uses several means, including hormones. The hormone ethylene has been known as a negative regulator of nodulation for almost four decades. Since then, much progress has been made in the understanding of both the ethylene signaling pathway and the nodulation process. Here I have taken a large view, using recently obtained knowledge, to describe in some detail the major stages of the process. I have not only reviewed the steps most commonly covered (the common signaling transduction pathway, and the epidermal and cortical programs), but I have also looked into steps less understood (the pre-infection step with the plant defense response, the bacterial release and the formation of the symbiosome, and nodule functioning and senescence). After a succinct review of the ethylene signaling pathway, I have used the knowledge obtained from nodulation- and ethylene-related mutants to paint a more complete picture of the role played by the hormone in nodule organogenesis, functioning, and senescence. It transpires that ethylene is at the center of this effective symbiosis. It has not only been involved in most of the steps leading to a mature nodule, but it has also been implicated in host immunity and nodule senescence. It is likely responsible for the activation of other hormonal signaling pathways. I have completed the review by citing three studies which makes one wonder whether knowledge gained on nodulation in the last decades is ready to be transferred to agricultural fields. PMID- 26834755 TI - Ammonium Inhibits Chromomethylase 3-Mediated Methylation of the Arabidopsis Nitrate Reductase Gene NIA2. AB - Gene methylation is an important mechanism regulating gene expression and genome stability. Our previous work showed that methylation of the nitrate reductase (NR) gene NIA2 was dependent on chromomethylase 3 (CMT3). Here, we show that CMT3 mediated NIA2 methylation is regulated by ammonium in Arabidopsis thaliana. CHG sequences (where H can be A, T, or C) were methylated in NIA2 but not in NIA1, and ammonium [(NH4)2SO4] treatment completely blocked CHG methylation in NIA2. By contrast, ammonium had no effect on CMT3 methylation, indicating that ammonium negatively regulates CMT3-mediated NIA2 methylation without affecting CMT3 methylation. Ammonium upregulated NIA2 mRNA expression, which was consistent with the repression of NIA2 methylation by ammonium. Ammonium treatment also reduced the overall genome methylation level of wild-type Arabidopsis. Moreover, CMT3 bound to specific promoter and intragenic regions of NIA2. These combined results indicate that ammonium inhibits CMT3-mediated methylation of NIA2 and that of other target genes, and CMT3 selectively binds to target DNA sequences for methylation. PMID- 26834756 TI - Pigeonpea Hybrid-Proline-Rich Protein (CcHyPRP) Confers Biotic and Abiotic Stress Tolerance in Transgenic Rice. AB - In this study, we report the overexpression of Cajanus cajan hybrid-proline-rich protein encoding gene (CcHyPRP) in rice which resulted in increased tolerance to both abiotic and biotic stresses. Compared to the control plants, the transgenic rice lines, expressing CcHyPRP, exhibited high-level tolerance against major abiotic stresses, viz., drought, salinity, and heat, as evidenced by increased biomass, chlorophyll content, survival rate, root, and shoot growth. Further, transgenic rice lines showed increased panicle size and grain number compared to the control plants under different stress conditions. The CcHyPRP transgenics, as compared to the control, revealed enhanced activities of catalase and superoxide dismutase (SOD) enzymes and reduced malondialdehyde (MDA) levels. Expression pattern of CcHyPRP::GFP fusion-protein confirmed its predominant localization in cell walls. Moreover, the CcHyPRP transgenics, as compared to the control, exhibited increased resistance to the fungal pathogen Magnaporthe grisea which causes blast disease in rice. Higher levels of bZIP and endochitinase transcripts as well as endochitinase activity were observed in transgenic rice compared to the control plants. The overall results demonstrate the intrinsic role of CcHyPRP in conferring multiple stress tolerance at the whole-plant level. The multipotent CcHyPRP seems promising as a prime candidate gene to fortify crop plants for enhanced tolerance/resistance to different stress factors. PMID- 26834754 TI - Multi-Omics Approach Identifies Molecular Mechanisms of Plant-Fungus Mycorrhizal Interaction. AB - In mycorrhizal symbiosis, plant roots form close, mutually beneficial interactions with soil fungi. Before this mycorrhizal interaction can be established however, plant roots must be capable of detecting potential beneficial fungal partners and initiating the gene expression patterns necessary to begin symbiosis. To predict a plant root-mycorrhizal fungi sensor systems, we analyzed in vitro experiments of Populus tremuloides (aspen tree) and Laccaria bicolor (mycorrhizal fungi) interaction and leveraged over 200 previously published transcriptomic experimental data sets, 159 experimentally validated plant transcription factor binding motifs, and more than 120-thousand experimentally validated protein-protein interactions to generate models of pre mycorrhizal sensor systems in aspen root. These sensor mechanisms link extracellular signaling molecules with gene regulation through a network comprised of membrane receptors, signal cascade proteins, transcription factors, and transcription factor biding DNA motifs. Modeling predicted four pre mycorrhizal sensor complexes in aspen that interact with 15 transcription factors to regulate the expression of 1184 genes in response to extracellular signals synthesized by Laccaria. Predicted extracellular signaling molecules include common signaling molecules such as phenylpropanoids, salicylate, and jasmonic acid. This multi-omic computational modeling approach for predicting the complex sensory networks yielded specific, testable biological hypotheses for mycorrhizal interaction signaling compounds, sensor complexes, and mechanisms of gene regulation. PMID- 26834757 TI - The Novel Wheat Transcription Factor TaNAC47 Enhances Multiple Abiotic Stress Tolerances in Transgenic Plants. AB - NAC transcription factors play diverse roles in plant development and responses to abiotic stresses. However, the biological roles of NAC family members in wheat are not well understood. Here, we reported the isolation and functional characterization of a novel wheat TaNAC47 gene. TaNAC47 encoded protein, localizing in the nucleus, is able to bind to the ABRE cis-element and transactivate transcription in yeast, suggesting that it likely functions as a transcriptional activator. We also showed that TaNAC47 is differentially expressed in different tissues, and its expression was induced by the stress treatments of salt, cold, polyethylene glycol and exogenous abscisic acid. Furthermore, overexpression of TaNAC47 in Arabidopsis resulted in ABA hypersensitivity and enhancing tolerance of transgenic plants to drought, salt, and freezing stresses. Strikingly, overexpression of TaNAC47 was found to activate the expression of downstream genes and change several physiological indices that may enable transgenic plants to overcome unfavorable environments. Taken together, these results uncovered an important role of wheat TaNAC47 gene in response to ABA and abiotic stresses. PMID- 26834758 TI - TaADF3, an Actin-Depolymerizing Factor, Negatively Modulates Wheat Resistance Against Puccinia striiformis. AB - The actin cytoskeleton has been implicated in plant defense against pathogenic fungi, oomycetes, and bacteria. Actin depolymerizing factors (ADFs) are stimulus responsive actin cytoskeleton modulators. However, there is limited evidence linking ADFs with plant defense against pathogens. In this study, we have isolated and functionally characterized a stress-responsive ADF gene (TaADF3) from wheat, which was detectable in all examined wheat tissues. TaADF3 is a three copy gene located on chromosomes 5AL, 5BL, and 5DL. A particle bombardment assay in onion epidermal cells revealed the cytoplasmic and nuclear localization of TaADF3. The expression of TaADF3 was inducible by abscisic acid (ABA), as well as various abiotic stresses (drought and cold) and virulent Puccinia striiformis f. sp. tritici (Pst) but was down regulated in response to avirulent Pst. Virus induced silencing of TaADF3 copies enhanced wheat resistance to avirulent Pst, with decreased reactive oxygen species (ROS) accumulation and hypersensitive response (HR). Upon treatment with virulent Pst, TaADF3-knockdown plants exhibited reduced susceptibility, which was accompanied by increased ROS production and HR. Interestingly, the silencing of TaADF3 resulted in hindered pathogen penetration and haustoria formation for both avirulent and virulent Pst. Moreover, the array and distribution of actin filaments was transformed in TaADF3 knockdown epidermal cells, which possibly facilitated attenuating the fungus penetration. Thus, our findings suggest that TaADF3 positively regulates wheat tolerance to abiotic stresses and negatively regulates wheat resistance to Pst in an ROS-dependent manner, possibly underlying the mechanism of impeding fungal penetration dependent on the actin architecture dynamics. PMID- 26834759 TI - The Role of Ethylene in Plant Adaptations for Phosphate Acquisition in Soils - A Review. AB - Although a role of ethylene in the regulation of senescence and plant stress responses in general has a long history, a possible involvement in the regulation of adaptive responses to nutrient deficiencies has been mainly investigated since the last two decades. In the case of plant responses to phosphate (Pi) starvation, ethylene was identified as a modulator of adaptive responses in root growth and morphology. The molecular base of these adaptations has been elucidated in supplementation studies with ethylene precursors and antagonists, as well as analysis of mutants and transgenic plants with modified ethylene biosynthesis and responsiveness, using mainly Arabidopsis thaliana as a model plant. However, increasing evidence suggests that apart from root growth responses, ethylene may be involved in various additional plant adaptations to Pi limitation including Pi mobilization in the rhizosphere, Pi uptake and internal Pi recycling. The ethylene-mediated responses are frequently characterized by high genotypic variability and may partially share common pathways in different nutrient limitations. PMID- 26834760 TI - Spatiotemporal Dynamics of Oligofructan Metabolism and Suggested Functions in Developing Cereal Grains. AB - Oligofructans represent one of the most important groups of sucrose-derived water soluble carbohydrates in the plant kingdom. In cereals, oligofructans accumulate in above ground parts of the plants (stems, leaves, seeds) and their biosynthesis leads to the formation of both types of glycosidic linkages [beta(2,1); beta(2,6) fructans] or mixed patterns. In recent studies, tissue- and development- specific distribution patterns of the various oligofructan types in cereal grains have been shown, which are possibly related to the different phases of grain development, such as cellular differentiation of grain tissues and storage product accumulation. Here, we summarize the current knowledge about oligofructan biosynthesis and accumulation kinetics in cereal grains. We focus on the spatiotemporal dynamics and regulation of oligofructan biosynthesis and accumulation in developing barley grains (deduced from a combination of metabolite, transcript and proteome analyses). Finally, putative physiological functions of oligofructans in developing grains are discussed. PMID- 26834761 TI - A De novo Transcriptomic Approach to Identify Flavonoids and Anthocyanins "Switch Off" in Olive (Olea europaea L.) Drupes at Different Stages of Maturation. AB - Highlights A de novo transcriptome reconstruction of olive drupes was performed in two genotypesGene expression was monitored during drupe development in two olive cultivarsTranscripts involved in flavonoid and anthocyanin pathways were analyzed in Cassanese and Leucocarpa cultivarsBoth cultivar and developmental stage impact gene expression in Olea europaea fruits. During ripening, the fruits of the olive tree (Olea europaea L.) undergo a progressive chromatic change characterized by the formation of a red-brown "spot" which gradually extends on the epidermis and in the innermost part of the mesocarp. This event finds an exception in the Leucocarpa cultivar, in which we observe a destabilized equilibrium between the metabolisms of chlorophyll and other pigments, particularly the anthocyanins whose switch-off during maturation promotes the white coloration of fruits. Despite its importance, genomic information on the olive tree is still lacking. Different RNA-seq libraries were generated from drupes of "Leucocarpa" and "Cassanese" olive genotypes, sampled at 100 and 130 days after flowering (DAF), and were used in order to identify transcripts involved in the main phenotypic changes of fruits during maturation and their corresponding expression patterns. A total of 103,359 transcripts were obtained and 3792 and 3064 were differentially expressed in "Leucocarpa" and "Cassanese" genotypes, respectively, during 100-130 DAF transition. Among them flavonoid and anthocyanin related transcripts such as phenylalanine ammonia lyase (PAL), cinnamate 4-hydroxylase (C4H), 4-coumarate-CoA ligase (4CL), chalcone synthase (CHS), chalcone isomerase (CHI), flavanone 3-hydroxylase (F3H), flavonol 3' hydrogenase (F3'H), flavonol 3'5 '-hydrogenase (F3'5'H), flavonol synthase (FLS), dihydroflavonol 4-reductase (DFR), anthocyanidin synthase (ANS), UDP glucose:anthocianidin: flavonoid glucosyltransferase (UFGT) were identified. These results contribute to reducing the current gap in information regarding metabolic processes, including those linked to fruit pigmentation in the olive. PMID- 26834763 TI - Quantitative Profiling of Feruloylated Arabinoxylan Side-Chains from Graminaceous Cell Walls. AB - Graminaceous arabinoxylans are distinguished by decoration with feruloylated monosaccharidic and oligosaccharidic side-chains. Although it is hypothesized that structural complexity and abundance of these feruloylated arabinoxylan side chains may contribute, among other factors, to resistance of plant cell walls to enzymatic degradation, quantitative profiling approaches for these structural units in plant cell wall materials have not been described yet. Here we report the development and application of a rapid and robust method enabling the quantitative comparison of feruloylated side-chain profiles in cell wall materials following mildly acidic hydrolysis, C18-solid phase extraction (SPE), reduction under aprotic conditions, and liquid chromatography with diode-array detection/mass spectrometry (LC-DAD/MS) separation and detection. The method was applied to the insoluble fiber/cell wall materials isolated from 12 whole grains: wild rice (Zizania aquatica L.), long-grain brown rice (Oryza sativa L.), rye (Secale cereale L.), kamut (Triticum turanicum Jakubz.), wheat (Triticum aestivum L.), spelt (Triticum spelta L.), intermediate wheatgrass (Thinopyrum intermedium), maize (Zea mays L.), popcorn (Zea mays L. var. everta), oat (Avena sativa L.) (dehulled), barley (Hordeum vulgare L.) (dehulled), and proso millet (Panicum miliaceum L.). Between 51 and 96% of the total esterified monomeric ferulates were represented in the quantified compounds captured in the feruloylated side-chain profiles, which confirms the significance of these structures to the global arabinoxylan structure in terms of quantity. The method provided new structural insights into cereal grain arabinoxylans, in particular, that the structural moiety alpha-l-galactopyranosyl-(1->2)-beta-d-xylopyranosyl (1->2)-5-O-trans-feruloyl-l-arabinofuranose (FAXG), which had previously only been described in maize, is ubiquitous to cereal grains. PMID- 26834762 TI - Genome-Wide Analysis of the AP2/ERF Superfamily Genes and their Responses to Abiotic Stress in Medicago truncatula. AB - The AP2/ERF superfamily is a large, plant-specific transcription factor family that is involved in many important processes, including plant growth, development, and stress responses. Using Medicago truncatula genome information, we identified and characterized 123 putative AP2/ERF genes, which were named as MtERF1-123. These genes were classified into four families based on phylogenetic analysis, which is consistent with the results of other plant species. MtERF genes are distributed throughout all chromosomes but are clustered on various chromosomes due to genomic tandem and segmental duplication. Using transcriptome, high-throughput sequencing data, and qRT-PCR analysis, we assessed the expression patterns of the MtERF genes in tissues during development and under abiotic stresses. In total, 87 MtERF genes were expressed in plant tissues, most of which were expressed in specific tissues during development or under specific abiotic stress treatments. These results support the notion that MtERF genes are involved in developmental regulation and environmental responses in M. truncatula. Furthermore, a cluster of DREB subfamily members on chromosome 6 was induced by both cold and freezing stress, representing a positive gene regulatory response under low temperature stress, which suggests that these genes might contribute to freezing tolerance to M. truncatula. In summary, our genome-wide characterization, evolutionary analysis, and expression pattern analysis of MtERF genes in M. truncatula provides valuable information for characterizing the molecular functions of these genes and utilizing them to improve stress tolerance in plants. PMID- 26834764 TI - Exogenous Classic Phytohormones Have Limited Regulatory Effects on Fructan and Primary Carbohydrate Metabolism in Perennial Ryegrass (Lolium perenne L.). AB - Fructans are polymers of fructose and one of the main constituents of water soluble carbohydrates in forage grasses and cereal crops of temperate climates. Fructans are involved in cold and drought resistance, regrowth following defoliation and early spring growth, seed filling, have beneficial effects on human health and are used for industrial processes. Perennial ryegrass (Lolium perenne L.) serves as model species to study fructan metabolism. Fructan metabolism is under the control of both synthesis by fructosyltransferases (FTs) and breakdown through fructan exohydrolases (FEHs). The accumulation of fructans can be triggered by high sucrose levels and abiotic stress conditions such as drought and cold stress. However, detailed studies on the mechanisms involved in the regulation of fructan metabolism are scarce. Since different phytohormones, especially abscisic acid (ABA), are known to play an important role in abiotic stress responses, the possible short term regulation of the enzymes involved in fructan metabolism by the five classical phytohormones was investigated. Therefore, the activities of enzymes involved in fructan synthesis and breakdown, the expression levels for the corresponding genes and levels for water-soluble carbohydrates were determined following pulse treatments with ABA, auxin (AUX), ethylene (ET), gibberellic acid (GA), or kinetin (KIN). The most pronounced fast effects were a transient increase of FT activities by AUX, KIN, ABA, and ET, while minor effects were evident for 1-FEH activity with an increased activity in response to KIN and a decrease by GA. Fructan and sucrose levels were not affected. This observed discrepancy demonstrates the importance of determining enzyme activities to obtain insight into the physiological traits and ultimately the plant phenotype. The comparative analyses of activities for seven key enzymes of primary carbohydrate metabolism revealed no co-regulation between enzymes of the fructan and sucrose pool. PMID- 26834767 TI - The Effects of Fe2O3 Nanoparticles on Physiology and Insecticide Activity in Non Transgenic and Bt-Transgenic Cotton. AB - As the demands for nanotechnology and nanoparticle (NP) applications in agriculture increase, the ecological risk has drawn more attention because of the unpredictable results of interactions between NPs and transgenic crops. In this study, we investigated the effects of various concentrations of Fe2O3 NPs on Bt transgenic cotton in comparison with conventional cotton for 10 days. Each treatment was conducted in triplicate, and each experiment was repeated three times. Results demonstrated that Fe2O3 NPs inhibited the plant height and root length of Bt-transgenic cotton and promoted root hairs and biomass of non transgenic cotton. Nutrients such as Na and K in Bt-transgenic cotton roots increased, while Zn contents decreased with Fe2O3 NPs. Most hormones in the roots of Bt-transgenic cotton increased at low Fe2O3 NP exposure (100 mg?L(-1)) but decreased at high concentrations of Fe2O3 NPs (1000 mg?L(-1)). Fe2O3 NPs increased the Bt-toxin in leaves and roots of Bt-transgenic cotton. Fe2O3 NPs were absorbed into roots, then transported to the shoots of both Bt-transgenic and non-transgenic cottons. The bioaccumulation of Fe2O3 NPs in plants might be a potential risk for agricultural crops and affect the environment and human health. PMID- 26834768 TI - Lipid Extracted Microalgal Biomass Residue as a Fertilizer Substitute for Zea mays L. AB - High volumes of lipid extracted microalgal biomass residues (LMBRs) are expected to be produced upon commencement of biodiesel production on a large scale, thus necessitating its value addition for sustainable development. LMBRs of Chlorella variabilis and Lyngbya majuscula were employed to substitute the nitrogen content of recommended rate of fertilizer (RRF) for Zea mays L. The pot experiment comprised of 10 treatments, i.e., T1 (No fertilizer); T2 (RRF-120 N: 60 P2O5: 40 K2O kg ha(-1)); T3 to T6-100, 75, 50, and 25% N through LMBR of the Chlorella sp., respectively; T7 to T10-100, 75, 50, and 25% N through LMBR of Lyngbya sp., respectively. It was found that all LMBR substitution treatments were at par to RRF with respect to grain yield production. T10 gave the highest grain yield (65.16 g plant(-1)), which was closely followed by that (63.48 g plant(-1)) under T5. T10 also recorded the highest phosphorus and potassium contents in grains. T4 was markedly superior over control in terms of dry matter accumulation (DMA) as well as carbohydrate content, which was ascribed to higher pigment content and photosynthetic activity in leaves. Even though considerably lower DMA was obtained in Lyngbya treatments, which might have been due to the presence of some toxic factors, no reduction in grain yield was apparent. The length of the tassel was significantly higher in either of the LMBRs at any substitution rates over RRF, except T6 and T7. The ascorbate peroxidase activity decreased with decreasing dose of Chlorella LMBR, while all the Lyngbya LMBR treatments recorded lower activity, which were at par with each other. Among the Chlorella treatments, only T5 recorded significantly higher values of glutathione reductase activity over RRF, while the rest were at par. There were significant increases in carbohydrate and crude fat, respectively, only in T4 and T3 over RRF, while no change was observed in crude protein due to LMBR treatments. Apparently, there was no detrimental effect on soil properties, suggesting that both the LMBRs can be employed to reduce the usage of chemical fertilizers, thus promoting maize crop production in a sustainable manner. PMID- 26834766 TI - De novo Transcriptome Sequencing and Development of Abscission Zone-Specific Microarray as a New Molecular Tool for Analysis of Tomato Organ Abscission. AB - Abscission of flower pedicels and leaf petioles of tomato (Solanum lycopersicum) can be induced by flower removal or leaf deblading, respectively, which leads to auxin depletion, resulting in increased sensitivity of the abscission zone (AZ) to ethylene. However, the molecular mechanisms that drive the acquisition of abscission competence and its modulation by auxin gradients are not yet known. We used RNA-Sequencing (RNA-Seq) to obtain a comprehensive transcriptome of tomato flower AZ (FAZ) and leaf AZ (LAZ) during abscission. RNA-Seq was performed on a pool of total RNA extracted from tomato FAZ and LAZ, at different abscission stages, followed by de novo assembly. The assembled clusters contained transcripts that are already known in the Solanaceae (SOL) genomics and NCBI databases, and over 8823 identified novel tomato transcripts of varying sizes. An AZ-specific microarray, encompassing the novel transcripts identified in this study and all known transcripts from the SOL genomics and NCBI databases, was constructed to study the abscission process. Multiple probes for longer genes and key AZ-specific genes, including antisense probes for all transcripts, make this array a unique tool for studying abscission with a comprehensive set of transcripts, and for mining for naturally occurring antisense transcripts. We focused on comparing the global transcriptomes generated from the FAZ and the LAZ to establish the divergences and similarities in their transcriptional networks, and particularly to characterize the processes and transcriptional regulators enriched in gene clusters that are differentially regulated in these two AZs. This study is the first attempt to analyze the global gene expression in different AZs in tomato by combining the RNA-Seq technique with oligonucleotide microarrays. Our AZ-specific microarray chip provides a cost-effective approach for expression profiling and robust analysis of multiple samples in a rapid succession. PMID- 26834769 TI - Heme Oxygenase-1 Delays Gibberellin-Induced Programmed Cell Death of Rice Aleurone Layers Subjected to Drought Stress by Interacting with Nitric Oxide. AB - Cereal aleurone layers undergo a gibberellin (GA)-regulated process of programmed cell death (PCD) following germination. Heme oxygenase-1 (HO-1) is known as a rate-liming enzyme in the degradation of heme to biliverdin IXalpha, carbon monoxide (CO), and free iron ions (Fe(2+)). It is a critical component in plant development and adaptation to environment stresses. Our previous studies confirmed that HO-1 inducer hematin (Ht) promotes the germination of rice seeds in drought (20% polyethylene glycol-6000, PEG) conditions, but the corresponding effects of HO-1 on the alleviation of germination-triggered PCD in GA-treated rice aleurone layers remain unknown. The present study has determined that GA co treated with PEG results in lower HO-1 transcript levels and HO activity, which in turn results in the development of vacuoles in aleurone cells, followed by PCD. The pharmacology approach illustrated that up- or down-regulated HO-1 gene expression and HO activity delayed or accelerated GA-induced PCD. Furthermore, the application of the HO-1 inducer Ht and nitric oxide (NO) donor sodium nitroprusside (SNP) not only activated HO-1 gene expression, HO activity, and endogenous NO content, but also blocked GA-induced rapid vacuolation and accelerated aleurone layers PCD under drought stress. However, both HO-1 inhibitor zinc protoporphyrin IX (ZnPPIX) and NO scavenger 2-(4-carboxyphenyl0-4, 4,5,5-tetramethylimidazoline-l-oxyl-3-oxide potassium salt (cPTIO) reserved the effects of Ht and SNP on rice aleurone layer PCD under drought stress by down regulating endogenous HO-1 and NO, respectively. The inducible effects of Ht and SNP on HO-1 gene expression, HO activity, and NO content were blocked by cPTIO. Together, these results clearly suggest that HO-1 is involved in the alleviation of GA-induced PCD of drought-triggered rice aleurone layers by associating with NO. PMID- 26834765 TI - Fluorescent Protein Aided Insights on Plastids and their Extensions: A Critical Appraisal. AB - Multi-colored fluorescent proteins targeted to plastids have provided new insights on the dynamic behavior of these organelles and their interactions with other cytoplasmic components and compartments. Sub-plastidic components such as thylakoids, stroma, the inner and outer membranes of the plastid envelope, nucleoids, plastoglobuli, and starch grains have been efficiently highlighted in living plant cells. In addition, stroma filled membrane extensions called stromules have drawn attention to the dynamic nature of the plastid and its interactions with the rest of the cell. Use of dual and triple fluorescent protein combinations has begun to reveal plastid interactions with mitochondria, the nucleus, the endoplasmic reticulum and F-actin and suggests integral roles of plastids in retrograde signaling, cell to cell communication as well as plant pathogen interactions. While the rapid advances and insights achieved through fluorescent protein based research on plastids are commendable it is necessary to endorse meaningful observations but subject others to closer scrutiny. Here, in order to develop a better and more comprehensive understanding of plastids and their extensions we provide a critical appraisal of recent information that has been acquired using targeted fluorescent protein probes. PMID- 26834771 TI - Corrigendum: Wrinkled1 Accelerates Flowering and Regulates Lipid Homeostasis between Oil Accumulation and Membrane Lipid Anabolism in Brassica napus. AB - [This corrects the article on p. 1015 in vol. 6, PMID: 26635841.]. PMID- 26834770 TI - Nitric Oxide-Mediated Maize Root Apex Responses to Nitrate are Regulated by Auxin and Strigolactones. AB - Nitrate (NO3 (-)) is a key element for crop production but its levels in agricultural soils are limited. Plants have developed mechanisms to cope with these NO3 (-) fluctuations based on sensing nitrate at the root apex. Particularly, the transition zone (TZ) of root apex has been suggested as a signaling-response zone. This study dissects cellular and molecular mechanisms underlying NO3 (-) resupply effects on primary root (PR) growth in maize, confirming nitric oxide (NO) as a putative modulator. Nitrate restoration induced PR elongation within the first 2 h, corresponding to a stimulation of cell elongation at the basal border of the TZ. Xyloglucans (XGs) immunolocalization together with Brefeldin A applications demonstrated that nitrate resupply induces XG accumulation. This effect was blocked by cPTIO (NO scavenger). Transcriptional analysis of ZmXET1 confirmed the stimulatory effect of nitrate on XGs accumulation in cells of the TZ. Immunolocalization analyses revealed a positive effect of nitrate resupply on auxin and PIN1 accumulation, but a transcriptional regulation of auxin biosynthesis/transport/signaling genes was excluded. Short term nitrate treatment repressed the transcription of genes involved in strigolactones (SLs) biosynthesis and transport, mainly in the TZ. Enhancement of carotenoid cleavage dioxygenases (CCDs) transcription in presence of cPTIO indicated endogenous NO as a negative modulator of CCDs activity. Finally, treatment with the SLs-biosynthesis inhibitor (TIS108) restored the root growth in the nitrate-starved seedlings. Present report suggests that the NO-mediated root apex responses to nitrate are accomplished in cells of the TZ via integrative actions of auxin, NO and SLs. PMID- 26834772 TI - Validating DNA Polymorphisms Using KASP Assay in Prairie Cordgrass (Spartina pectinata Link) Populations in the U.S. AB - Single nucleotide polymorphisms (SNPs) are one of the most abundant DNA variants found in plant genomes and are highly efficient when comparing genome and transcriptome sequences. SNP marker analysis can be used to analyze genetic diversity, create genetic maps, and utilize marker-assisted selection breeding in many crop species. In order to utilize these technologies, one must first identify and validate putative SNPs. In this study, 121 putative SNPs, developed from a nuclear transcriptome of prairie cordgrass (Spartina pectinata Link), were analyzed using KASP technology in order to validate the SNPs. Fifty-nine SNPs were validated using a core collection of 38 natural populations and a phylogenetic tree was created with one main clade. Samples from the same population tended to cluster in the same location on the tree. Polymorphisms were identified within 52.6% of the populations, split evenly between the tetraploid and octoploid cytotypes. Twelve selected SNP markers were used to assess the fidelity of tetraploid crosses of prairie cordgrass and their resulting F2population. These markers were able to distinguish true crosses and selfs. This study provides insight into the genomic structure of prairie cordgrass, but further analysis must be done on other cytotypes to fully understand the structure of this species. This study validates putative SNPs and confirms the potential usefulness of SNP marker technology in future breeding programs of this species. PMID- 26834773 TI - Genome-Wide Small RNA Analysis of Soybean Reveals Auxin-Responsive microRNAs that are Differentially Expressed in Response to Salt Stress in Root Apex. AB - Root growth and the architecture of the root system in Arabidopsis are largely determined by root meristematic activity. Legume roots show strong developmental plasticity in response to both abiotic and biotic stimuli, including symbiotic rhizobia. However, a global analysis of gene regulation in the root meristem of soybean plants is lacking. In this study, we performed a global analysis of the small RNA transcriptome of root tips from soybean seedlings grown under normal and salt stress conditions. In total, 71 miRNA candidates, including known and novel variants of 59 miRNA families, were identified. We found 66 salt-responsive miRNAs in the soybean root meristem; among them, 22 are novel miRNAs. Interestingly, we found auxin-responsive cis-elements in the promoters of many salt-responsive miRNAs, implying that these miRNAs may be regulated by auxin and auxin signaling plays a key role in regulating the plasticity of the miRNAome and root development in soybean. A functional analysis of miR399, a salt-responsive miRNA in the root meristem, indicates the crucial role of this miRNA in modulating soybean root developmental plasticity. Our data provide novel insight into the miRNAome-mediated regulatory mechanism in soybean root growth under salt stress. PMID- 26834774 TI - Overexpression of a Stress-Responsive NAC Transcription Factor Gene ONAC022 Improves Drought and Salt Tolerance in Rice. AB - The NAC transcription factors play critical roles in regulating stress responses in plants. However, the functions for many of the NAC family members in rice are yet to be identified. In the present study, a novel stress-responsive rice NAC gene, ONAC022, was identified. Expression of ONAC022 was induced by drought, high salinity, and abscisic acid (ABA). The ONAC022 protein was found to bind specifically to a canonical NAC recognition cis-element sequence and showed transactivation activity at its C-terminus in yeast. The ONAC022 protein was localized to nucleus when transiently expressed in Nicotiana benthamiana. Three independent transgenic rice lines with overexpression of ONAC022 were generated and used to explore the function of ONAC022 in drought and salt stress tolerance. Under drought stress condition in greenhouse, soil-grown ONAC022-overexpressing (N22oe) transgenic rice plants showed an increased drought tolerance, leading to higher survival ratios and better growth than wild-type (WT) plants. When grown hydroponically in Hogland solution supplemented with 150 mM NaCl, the N22oe plants displayed an enhanced salt tolerance and accumulated less Na(+) in roots and shoots as compared to WT plants. Under drought stress condition, the N22oe plants exhibited decreased rates of water loss and transpiration, reduced percentage of open stomata and increased contents of proline and soluble sugars. However, the N22oe lines showed increased sensitivity to exogenous ABA at seed germination and seedling growth stages but contained higher level of endogenous ABA. Expression of some ABA biosynthetic genes (OsNCEDs and OsPSY), signaling and regulatory genes (OsPP2C02, OsPP2C49, OsPP2C68, OsbZIP23, OsAP37, OsDREB2a, and OsMYB2), and late stress-responsive genes (OsRAB21, OsLEA3, and OsP5CS1) was upregulated in N22oe plants. Our data demonstrate that ONAC022 functions as a stress-responsive NAC with transcriptional activator activity and plays a positive role in drought and salt stress tolerance through modulating an ABA mediated pathway. PMID- 26834775 TI - Molecular Characterization of FT and FD Homologs from Eriobotrya deflexa Nakai forma koshunensis. AB - In angiosperms, regulation of flowering is a vital process for successful reproduction. To date, the molecular mechanism of flowering is well-studied in the model plant, Arabidopsis, in which key genes such as FLOWERING LOCUST (FT) or FD have been identified to regulate flowering. However, the flowering mechanisms are still largely unknown in fruit trees like loquat. To this end, we first cloned one FT- and two FD-like genes from the loquat (Eriobotrya deflexa Nakai f. koshunensis) and referred to as EdFT, EdFD1, and EdFD2, respectively. Phylogenetic analysis has shown that EdFT, EdFD1, and EdFD2 are conserved during the evolution process. EdFT is mainly expressed in reproductive tissues (e.g., flower buds, flowers, and fruits), while EdFD1 and EdFD2 are mainly expressed in apical buds including leaf buds and flower buds. EdFT is localized in the whole cell, while EdFD1 or EdFD2 is localized in the nucleus. Ectopic expression of EdFT, EdFD1, and EdFD2 in Arabidopsis results in early flowering. In addition, we have also revealed that the EdFT interacts with both EdFD1 and EdFD2. Overall, these data suggest that the EdFT, EdFD1, and EdFD2 are the functional homologs of FT and FD, respectively, which might act together to regulate loquat flowering through a similar mechanism found in Arabidopsis. PMID- 26834776 TI - Fruit Ripening Regulation of alpha-Mannosidase Expression by the MADS Box Transcription Factor RIPENING INHIBITOR and Ethylene. AB - alpha-Mannosidase (alpha-Man), a fruit ripening-specific N-glycan processing enzyme, is involved in ripening-associated fruit softening process. However, the regulation of fruit-ripening specific expression of alpha-Man is not well understood. We have identified and functionally characterized the promoter of tomato (Solanum lycopersicum) alpha-Man to provide molecular insights into its transcriptional regulation during fruit ripening. Fruit ripening-specific activation of the alpha-Man promoter was revealed by analysing promoter driven expression of beta-glucuronidase (GUS) reporter in transgenic tomato. We found that RIPENING INHIBITOR (RIN), a MADS box family transcription factor acts as positive transcriptional regulator of alpha-Man during fruit ripening. RIN directly bound to the alpha-Man promoter sequence and promoter activation/alpha Man expression was compromised in rin mutant fruit. Deletion analysis revealed that a promoter fragment (567 bp upstream of translational start site) that contained three CArG boxes (binding sites for RIN) was sufficient to drive GUS expression in fruits. In addition, alpha-Man expression was down-regulated in fruits of Nr mutant which is impaired in ethylene perception and promoter activation/alpha-Man expression was induced in wild type following treatment with a precursor of ethylene biosynthesis, 1-aminocyclopropane-1-carboxylic acid (ACC). Although, alpha-Man expression was induced in rin mutant after ACC treatment, the transcript level was less as compared to ACC-treated wild type. Taken together, these results suggest RIN-mediated direct transcriptional regulation of alpha-Man during fruit ripening and ethylene may acts in RIN dependent and -independent ways to regulate alpha-Man expression. PMID- 26834777 TI - Fruiting Branch K(+) Level Affects Cotton Fiber Elongation Through Osmoregulation. AB - Potassium (K) deficiency in cotton plants results in reduced fiber length. As one of the primary osmotica, K(+) contributes to an increase in cell turgor pressure during fiber elongation. Therefore, it is hypothesized that fiber length is affected by K deficiency through an osmotic pathway, so in 2012 and 2013, an experiment was conducted to test this hypothesis by imposing three potassium supply regimes (0, 125, 250 kg K ha(-1)) on a low-K-sensitive cultivar, Siza 3, and a low-K-tolerant cultivar, Simian 3. We found that fibers were longer in the later season bolls than in the earlier ones in cotton plants grown under normal growth conditions, but later season bolls showed a greater sensitivity to low-K stress, especially the low-K sensitive genotype. We also found that the maximum velocity of fibre elongation (V max) is the parameter that best reflects the change in fiber elongation under K deficiency. This parameter mostly depends on cell turgor, so the content of the osmotically active solutes was analyzed accordingly. Statistical analysis showed that K(+) was the major osmotic factor affecting fiber length, and malate was likely facilitating K(+) accumulation into fibers, which enabled the low-K-tolerant genotype to cope with low-K stress. Moreover, the low-K-tolerant genotype tended to have greater K(+) absorptive capacities in the upper fruiting branches. Based on our findings, we suggest a fertilization scheme for Gossypium hirsutum that adds extra potash fertilizer or distributes it during the development of late season bolls to mitigate K deficiency in the second half of the growth season and to enhance fiber length in late season bolls. PMID- 26834778 TI - Enhanced Salt Tolerance Conferred by the Complete 2.3 kb cDNA of the Rice Vacuolar Na(+)/H(+) Antiporter Gene Compared to 1.9 kb Coding Region with 5' UTR in Transgenic Lines of Rice. AB - Soil salinity is one of the most challenging problems that restricts the normal growth and production of rice worldwide. It has therefore become very important to produce more saline tolerant rice varieties. This study shows constitutive over-expression of the vacuolar Na(+)/H(+) antiporter gene (OsNHX1) from the rice landrace (Pokkali) and attainment of enhanced level of salinity tolerance in transgenic rice plants. It also shows that inclusion of the complete un translated regions (UTRs) of the alternatively spliced OsNHX1 gene provides a higher level of tolerance to the transgenic rice. Two separate transformation events of the OsNHX1 gene, one with 1.9 kb region containing the 5' UTR with CDS and the other of 2.3 kb, including 5' UTR, CDS, and the 3' UTR regions were performed. The transgenic plants with these two different constructs were advanced to the T3 generation and physiological and molecular screening of homozygous plants was conducted at seedling and reproductive stages under salinity (NaCl) stress. Both transgenic lines were observed to be tolerant compared to WT plants at both physiological stages. However, the transgenic lines containing the CDS with both the 5' and 3' UTR were significantly more tolerant compared to the transgenic lines containing OsNHX1 gene without the 3' UTR. At the seedling stage at 12 dS/m stress, the chlorophyll content was significantly higher (P < 0.05) and the electrolyte leakage significantly lower (P < 0.05) in the order 2.3 kb > 1.9 kb > and WT lines. Yield in g/plant in the best line from the 2.3 kb plants was significantly more (P < 0.01) compared, respectively, to the best 1.9 kb line and WT plants at stress of 6 dS/m. Transformation with the complete transcripts rather than the CDS may therefore provide more durable level of tolerance. PMID- 26834779 TI - Plant Pathogens Affecting the Establishment of Plant-Symbiont Interaction. PMID- 26834780 TI - Great Desire for Extended Life and Health amongst the American Public. AB - People want to live long, healthy lives. Previous surveys suggest very limited interest in much longer lifespans, but we show that stipulating good health changes responses to favor longer lives by an order of magnitude. Advances in aging research hold out hope for greatly slowed aging with associated good health. Understanding the public's desires correctly is important to avoid misallocation of resources for research. PMID- 26834782 TI - Incorporating prior knowledge induced from stochastic differential equations in the classification of stochastic observations. AB - In classification, prior knowledge is incorporated in a Bayesian framework by assuming that the feature-label distribution belongs to an uncertainty class of feature-label distributions governed by a prior distribution. A posterior distribution is then derived from the prior and the sample data. An optimal Bayesian classifier (OBC) minimizes the expected misclassification error relative to the posterior distribution. From an application perspective, prior construction is critical. The prior distribution is formed by mapping a set of mathematical relations among the features and labels, the prior knowledge, into a distribution governing the probability mass across the uncertainty class. In this paper, we consider prior knowledge in the form of stochastic differential equations (SDEs). We consider a vector SDE in integral form involving a drift vector and dispersion matrix. Having constructed the prior, we develop the optimal Bayesian classifier between two models and examine, via synthetic experiments, the effects of uncertainty in the drift vector and dispersion matrix. We apply the theory to a set of SDEs for the purpose of differentiating the evolutionary history between two species. PMID- 26834783 TI - Precise periodic components estimation for chronobiological signals through Bayesian Inference with sparsity enforcing prior. AB - The toxicity and efficacy of more than 30 anticancer agents present very high variations, depending on the dosing time. Therefore, the biologists studying the circadian rhythm require a very precise method for estimating the periodic component (PC) vector of chronobiological signals. Moreover, in recent developments, not only the dominant period or the PC vector present a crucial interest but also their stability or variability. In cancer treatment experiments, the recorded signals corresponding to different phases of treatment are short, from 7 days for the synchronization segment to 2 or 3 days for the after-treatment segment. When studying the stability of the dominant period, we have to consider very short length signals relative to the prior knowledge of the dominant period, placed in the circadian domain. The classical approaches, based on Fourier transform (FT) methods are inefficient (i.e., lack of precision) considering the particularities of the data (i.e., the short length). Another particularity of the signals considered in such experiments is the level of noise: such signals are very noisy and establishing the periodic components that are associated with the biological phenomena and distinguishing them from the ones associated with the noise are difficult tasks. In this paper, we propose a new method for the estimation of the PC vector of biomedical signals, using the biological prior informations and considering a model that accounts for the noise. The experiments developed in cancer treatment context are recording signals expressing a limited number of periods. This is a prior information that can be translated as the sparsity of the PC vector. The proposed method considers the PC vector estimation as an Inverse Problem (IP) using the general Bayesian inference in order to infer the unknown of our model, i.e. the PC vector but also the hyperparameters (i.e the variances). The sparsity prior information is modeled using a sparsity enforcing prior law. In this paper, we propose a Student's t distribution, viewed as the marginal distribution of a bivariate normal-inverse gamma distribution. We build a general infinite Gaussian scale mixture (IGSM) hierarchical model where we assign prior distributions also for the hyperparameters. The expression of the joint posterior law of the unknown PC vector and hyperparameters is obtained via Bayes rule, and then, the unknowns are estimated via joint maximum a posteriori (JMAP) or posterior mean (PM). For the PM estimator, the expression of the posterior distribution is approximated by a separable one, via variational Bayesian approximation (VBA), using the Kullback Leibler (KL) divergence. For the PM estimation, two possibilities are considered: an approximation with a partially separable distribution and an approximation with a fully separable one. Both resulting algorithms corresponding to the PM estimation and the one corresponding to the JMAP estimation are iterative algorithms. The algorithms are presented in detail and are compared with the ones corresponding to the Gaussian model. We examine the convergency of the algorithms and give simulation results to compare their performances. Finally, we show simulation results on synthetic and real data in cancer treatment applications. The real data considered in this paper examines the rest-activity patterns of KI/KI Per2::luc mouse, aged 10 weeks, singly housed in RealTime Biolumicorder (RT BIO). PMID- 26834786 TI - Comment to "Telaprevir Experience From Turkey". PMID- 26834781 TI - Barth Syndrome: From Mitochondrial Dysfunctions Associated with Aberrant Production of Reactive Oxygen Species to Pluripotent Stem Cell Studies. AB - Mutations in the gene encoding the enzyme tafazzin, TAZ, cause Barth syndrome (BTHS). Individuals with this X-linked multisystem disorder present cardiomyopathy (CM) (often dilated), skeletal muscle weakness, neutropenia, growth retardation, and 3-methylglutaconic aciduria. Biopsies of the heart, liver and skeletal muscle of patients have revealed mitochondrial malformations and dysfunctions. It is the purpose of this review to summarize recent results of studies on various animal or cell models of Barth syndrome, which have characterized biochemically the strong cellular defects associated with TAZ mutations. Tafazzin is a mitochondrial phospholipidlysophospholipid transacylase that shuttles acyl groups between phospholipids and regulates the remodeling of cardiolipin (CL), a unique inner mitochondrial membrane phospholipid dimer consisting of two phosphatidyl residues linked by a glycerol bridge. After their biosynthesis, the acyl chains of CLs may be modified in remodeling processes involving up to three different enzymes. Their characteristic acyl chain composition depends on the function of tafazzin, although the enzyme itself surprisingly lacks acyl specificity. CLs are crucial for correct mitochondrial structure and function. In addition to their function in the basic mitochondrial function of ATP production, CLs play essential roles in cardiac function, apoptosis, autophagy, cell cycle regulation and Fe-S cluster biosynthesis. Recent developments in tafazzin research have provided strong insights into the link between mitochondrial dysfunction and the production of reactive oxygen species (ROS). An important tool has been the generation of BTHS-specific induced pluripotent stem cells (iPSCs) from BTHS patients. In a complementary approach, disease-specific mutations have been introduced into wild-type iPSC lines enabling direct comparison with isogenic controls. iPSC-derived cardiomyocytes were then characterized using biochemical and classical bioenergetic approaches. The cells are tested in a "heart-on-chip" assay to model the pathophysiology in vitro, to characterize the underlying mechanism of BTHS deriving from TAZ mutations, mitochondrial deficiencies and ROS production and leading to tissue defects, and to evaluate potential therapies with the use of mitochondrially targeted antioxidants. PMID- 26834785 TI - Persistence of Anti-HBs Among Palestinian Medical Students After 18 - 22 Years of Vaccination: A Cross-Sectional Study. AB - BACKGROUND: Hepatitis B infection is a global public health problem affecting various sectors in the society. Vaccination is the first line measure to prevent the disease. OBJECTIVES: To assess the persistence of anti-HBs marker among medical students after 18 - 22 of vaccination as an indicator for Hepatitis B virus vaccine efficacy. PATIENTS AND METHODS: In this study, 249 Palestinian medical students vaccinated at birth, 1, and 6 months of age using EngerixTM-B starting from 1992 were studied. About 58% (144/249) of the students were Palestinians holding Israeli citizenship, while 42% (105/249) were Palestinians from the West Bank. Students were tested serologically for anti-HBs, as a marker for vaccine-induced immunity. RESULTS: Over 75% (188/248) of students had levels of anti-HBs greater than 10 mIU/mL indicating immunity and protection. Five cases had positive results for anti-HBc indicating exposure to HBV infection; however, none of these cases showed any sign of HBV-DNA indicating effective clearance of the virus by the vaccine. Around 57% of the study group had anti-HBs level of 100 - 1000 mIU/mL. No significant association was found between anti-HBs level and age, sex, locality and level of anti-HBc (P > 0.05). The students were aware of different aspects of hepatitis B infection regarding the virus, symptoms, prevention and mode of transmission. CONCLUSIONS: The Palestinian and Israeli official policies to give a booster dose for risk groups like medical students at anti-HBs level below 10 mIU/mL should continue to ensure absolute protection. The currently-used vaccine and its time program cleared virus from students believed to have been exposed to the virus during their lifetime. PMID- 26834784 TI - Hepatitis E Virus Seroprevalence Among Blood Donors in Bushehr, South of Iran. AB - BACKGROUND: Although so far several studies have determined the hepatitis E virus (HEV) prevalence in some parts of Iran, no data exists regarding the HEV seroprevalence in Bushehr province as the southernmost point in Iran yet. OBJECTIVES: The aim of this study was to evaluate the seroprevalence of anti-HEV IgG among the blood donors in Bushehr. PATIENTS AND METHODS: A total of 628 blood donor samples were collected from September to October 2013, after obtaining informed written consents, and analyzed for the presence of anti-HEV IgG using commercial HEV enzyme-linked immunosorbent assay (ELISA) kit. All the samples were tested by two ELISA kits and evaluated for liver function test. RESULTS: Overall, 105 (16.7%) blood samples were positive for HEV-specific-IgG antibodies, while 523 (83.8%) were negative. The presence of anti-HEV IgG was not associated with gender; however, it was correlated with age. It was indicated that the anti HEV prevalence increases by age and there was a significant difference between the age groups regarding HEV seropositivity. CONCLUSIONS: High HEV seroprevalence (16.7%) was observed among the blood donors in Bushehr province. It appears that exposure to HEV increases with age; although, more people should be examined. PMID- 26834787 TI - Tumor Suppressor DLEC1 can Stimulate the Proliferation of Cancer Cells When AP 2alpha2 is Down-Regulated in HCT116. AB - BACKGROUND: The molecular mechanisms of tumor suppressor gene DLEC1 are largely unknown. OBJECTIVES: In this study, we established DLEC1 over-expression stable clones to study the cellular function of DLEC1 in the colorectal cancer cell line, HCT116. MATERIALS AND METHODS: Stable clones with DLEC1 over-expression were first established by the transfection of DLEC1 expression construct pcDNA31DLEC1 in HCT116. On G418 selection, positive stable clones were screened for DLEC1 expression level by conventional reverse transcription-polymerase chain reaction (RT-PCR), and verified by real-time RT-PCR and Western blotting. Subsequently, these stable clones were subjected to colony formation and cell cycle analyses and identification of factors involved in G1 arrest. Lastly, three stable clones, DLEC1-7 (highest DLEC1 expression), DLEC1-3 (lowest expression) and pcDNA31 vector control, were employed to analyze cell proliferation and cell cycle after AP-2alpha2 knockdown by siRNAs. RESULTS: The DLEC1 over-expression was found to reduce the number of colonies in colony formation and to induce G1 arrest in seven clones, and apoptosis in one clone in the cell cycle analysis. Furthermore, regardless of the different cell cycle defects in all eight stable clones, the expression level of transcriptional factor AP-2alpha2 was found to be elevated. More interestingly, we found that when AP-2alpha2 was knocked down, DLEC1 over-expression neither suppressed cancer cell growth nor induced G1 arrest, yet, instead promoted cell growth and decreased cells in the G1 fraction. This promotion of cell proliferation and release of G1 cells also seemed to be proportional to DLEC1 expression levels in DLEC1 stable clones. CONCLUSIONS: DLEC1 suppresses tumor cell growth the presence of AP-2alpha2 and stimulates cell proliferation in the down-regulation of AP-2alpha2 in DLEC1 over-expression stable clones of HTC116. PMID- 26834789 TI - Neutrophil Elastase Inhibitor Following Liver Resection: A Matched Cohort Study. AB - BACKGROUND: Sivelestat is a neutrophil elastase inhibitor (NEI) with positive impact on the respiratory complications in thoracic surgery. Based on the findings of a recent study, NEI may have a good response for avoiding ischemia reperfusion injury in liver resection. OBJECTIVES: The current study aimed to examine the impact of NEI on the postoperative outcomes after liver resection. PATIENTS AND METHODS: The data were collected from 374 consecutive patients scheduled to undergo liver resection. Seven perioperative variables were matched on the basis of the patients' background. Then, the NEI (n = 61) and control (n = 61) groups were compared. NEI was administered at a dose of 0.2 mg/kg/h for three days from the postoperative day 0 (POD0). The liver function, coagulation activity, inflammatory response, respiratory complications, and overall complications were compared. RESULTS: The levels of serum interleukin-6 (NEI group: 113 pg/mL [26.9 - 522.0] vs. control group: 174 [28.6 - 1040.6], P < 0.01) and C-reactive protein (CRP) (2.9 IU/L [range: 0.1 - 8.6] vs. 4.11 [0.3 - 13.8], P = 0.01) on the first postoperative day (POD1) and the alveolar-arterial oxygen tension difference (32.3 Torr [-28.6 - 132.3] vs. 46.6 [-11.2 - 251.6], P = 0.04) on the third postoperative day (POD3) were significantly lower in the NEI group than the control group. The rate of pleural effusion was significantly lower in the NEI group compared to that of the control group [13 patients (21.3%) vs. 23 (37.7%), P = 0.04]. However, the coagulation activities (P = 0.68), liver function (P = 0.69), non-respiratory complications (P = 0.84), and overall complications (P = 0.71) did not differ significantly between the groups. CONCLUSIONS: Intravenous NEI administration had positive impact on the postoperative inflammatory response and oxygenation while it did not affect either coagulation or the liver function, as well as severe grade complications following resection. PMID- 26834788 TI - Relative Expression of Toll-Like Receptors 2 and 7 mRNA in Peripheral Blood of Patients With Hepatitis C. AB - BACKGROUND: Hepatitis C virus (HCV) is an important human pathogen affecting an estimated 120 - 170 million individuals in the world. Toll-Like receptors (TLRs) are pattern-recognition receptors that recognize pathogen-associated molecular patterns, and stimulate immune responses. OBJECTIVES: The aim of this study was to determine the mRNA expression level of TLR2 and TLR7 in HCV-infected patients in comparison with normal controls. PATIENTS AND METHODS: Nineteen consecutive patients with HCV infection and nineteen sex and age-matched healthy controls were studied in a case-controlled research. RESULTS: Our results showed that the expressions of TLR7 in HCV infected samples were significantly increased in comparison those of the controls (P = 0.02), while the expression of TLR2 was similar between the case and the control group (P = 0.8). There were no associations between the expression levels of TLR2 and TLR7 with HCV viral load and HCV genotypes. Also, there was no association between viral load and genotypes of the virus. CONCLUSIONS: Our findings showed that HCV infection could lead to increased expression level of TLR7 mRNA in peripheral blood cells of HCV infected samples. The viral load and genotypes of HCV did not affect the mRNA expression levels of TLR2 and TLR7. PMID- 26834790 TI - Trends in the Burden of Hepatitis B in a Southern Brazilian State. AB - BACKGROUND: Viral hepatitis is a major health problem in Brazil and worldwide. The state of Santa Catarina has high endemic areas, and the disease burden is unknown. OBJECTIVES: To estimate and analyze the burden of hepatitis B in the state of Santa Catarina, in 2005 - 2010. MATERIALS AND METHODS: A time-series analysis was conducted using notification data of incidence and mortality rates from hepatitis B. The Disability-Adjusted Life Years (DALY) and the components Years of Life Lost (YLL) and Years Lived with Disability (YLD) were calculated. The annual variation was estimated using segmented linear regression, identifying the points at which there were changes in the trend. RESULTS: The state of Santa Catarina showed an increase of 11.9% (95% CI 0.9, 24.2) per year in YLL rates. A significant increase was observed for men and within the 70 - 79 age group. There was a significant decrease of -9.4% (95% CI -16.1, -2.2) in the YLD rates per year. The decline was significant for women and within the 15-34 age group. Regarding the DALY rates, the state of Santa Catarina showed a decline of -6.6% (95% CI: -11.0, -2.0) per year. Significant decreases occurred for females and within the 15 - 29 and 45 - 59 age groups. However, there was a significant increase within the 70 - 79 age range. CONCLUSIONS: The state of Santa Catarina has reduced the disease burden rates attributed to disability from hepatitis B, but there has been an increase in the burden of premature mortality from 2005 to 2010. PMID- 26834791 TI - A Meta-Analysis of the Association Between the I148M Variant of Patatin-Like Phospholipase Domain Containing 3 Gene and the Presence of Chronic Hepatitis C. AB - CONTEXT: The objective of the current study was to evaluate the association between the I148M variant of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and the presence of Chronic Hepatitis C (CHC) across different populations. EVIDENCE ACQUISITION: This study was a meta-analysis of all relevant researches published in the literature from year 2000 to 2015. The odds ratios (ORs) of PNPLA3 allele distributions in CHC patients were analyzed and compared with healthy controls. The meta-analysis Revman 5.2 software was applied for investigating heterogeneity among individual studies and for summarizing all the studies. The meta-analysis was carried out according to the Cochrane Reviewers' Handbook recommendations. A total of 120 clinical trials or reports were retrieved, yet only five trials met the study selection criteria. RESULTS: Five hospital-based case-control studies were included in the final analysis. The overall frequency of PNPLA3 gene polymorphisms was 20.4% (205/1005) in CHC and 10.23% (53/518) in controls. The summary odds ratio for the association of gene polymorphisms of PNPLA3 with the risk for CHC was determined as 2.20 (95% CI: 1.56 -3.11) and was statistically significant (P < 0.05). CONCLUSIONS: The current meta-analysis showed an association between frequency of GG genotype of PNPLA3 and the risk of development of CHC in various populations throughout the world. PMID- 26834792 TI - Effects of Pentoxifylline on Non-Alcoholic Steatohepatitis: A Randomized, Double Blind, Placebo-Controlled Trial in Iran. AB - BACKGROUND: Non-alcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease. Several studies suggest that pentoxifylline (PTX) can improve the disease outcome. OBJECTIVES: We aimed to compare the effect of pentoxifylline with placebo on liver aminotransferases and cytokines, including interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and interleukin 8 (IL-8) in patients with NASH. PATIENTS AND METHODS: Thirty patients with NASH were included in the study, based on ultrasonography and 1.5-fold mean change from baseline serum levels of liver aminotransferases. Patients with NASH were randomized to receive 1200 mg PTX (the intervention group) or placebo (the placebo group) for 6 months. The serum levels of liver aminotransferases and cytokines were compared between the intervention and placebo groups, at various time points. RESULTS: The serum levels of liver aminotransferases were significantly reduced at 3 months and at 6 months, compared with baseline, in both groups. The serum levels of IL-6 were significantly decreased, in both groups, only at 6 months, compared with baseline. Compared to the placebo group, the serum level of TNF-alpha was significantly decreased in the intervention group, at 6 months. The serum level of IL-8 was increased, in both groups, after 6 months, without reaching clinical significance. There was no significant difference in serum levels of liver aminotransferases and cytokines, between intervention and placebo groups. CONCLUSIONS: Decreases in the serum levels of liver aminotransferases and cytokines, in both groups, are related to low-calorie diets and exercise, rather than PTX. PMID- 26834793 TI - Association Between the Severity of Nocturnal Hypoxia in Obstructive Sleep Apnea and Non-Alcoholic Fatty Liver Damage. AB - BACKGROUND: Obstructive sleep apnea (OSA) is a major disease that can cause significant mortality and morbidity. Chronic intermittent hypoxia is a potential causal factor in the progression from fatty liver to nonalcoholic steatohepatitis. OBJECTIVES: This study evaluated the association between the degree of liver steatosis and severity of nocturnal hypoxia. PATIENTS AND METHODS: In this study, between December 2011 and December 2013, patients with ultrasound-diagnosed NAFLD evaluated by standart polysomnography were subsequentally recorded. Patients with alcohol use, viral hepatitis and other chronic liver diseases were excluded. We analyzed polysomnographic parameters, steatosis level and severity of obstructive sleep apnea (OSA) in consideration of body mass index (BMI), biochemical tests and ultrasonographic liver data of 137 subjects. Patients with sleep apnea and AHI scores of < 5, 5 - 14, 15 - 29 and >=30 are categorized as control, mild, moderate and severe, respectively. RESULTS: One hundred and thirty-seven patients (76 women, 61 men) with a mean age of 55.75 +/- 10.13 years who underwent polysomnography were included in the study. Of 118 patients diagnosed with OSA, 19 (16.1%) had mild OSA, 39 (33.1%) moderate OSA and 60 (50.8%) severe OSA. Nineteen cases formed the control group. Apnea/hypopnea index and oxygen desaturation index (ODI) values were significantly higher in moderate and severe non-alcoholic fatty liver disease (NAFLD) compared to the non-NAFLD group. Mean nocturnal SpO2 values were significantly lower in mild NAFLD and severe NAFLD compared to the non-NAFLD group. Lowest O2 saturation (LaSO2) was found low in mild, moderate and severe NAFLD compared to the non-NAFLD group in a statistically significant manner. CONCLUSIONS: We assessed polysomnographic parameters of AHI, ODI, LaSO2 and mean nocturnal SpO2 levels, which are especially important in the association between NAFLD and OSAS. We think that it is necessary to be attentive regarding NAFLD development and progression in patients with OSA whose nocturnal hypoxia is severe. PMID- 26834794 TI - Occult Hepatitis C Infection Should Be More Noticed With New Treatment Strategies. PMID- 26834795 TI - Comparison of Family Power Structure and Identity Style Between Delinquent and Non-Delinquent Juveniles. AB - BACKGROUND: Adolescence denotes a time in which youth begins to experience dangerous behaviors like substance use and delinquency. OBJECTIVES: In this study, we investigated the family power structure and identity style in delinquent and non-delinquent juveniles residing in Tehran, Iran. MATERIALS AND METHODS: To accomplish the goal of the study, 80 adolescent delinquents of the correction and rehabilitation centers aged between 15 and 18 years were selected with convenience sampling method and 80 students of secondary school age between 15 and 18 years in Tehran, Iran in 2012. They answered the instrument of family power structure (Saidian, 2004) and identity style (ISI-6G: White et al. 1998). The obtained data were analyzed using the independent t-test, chi-square test, and Levene's test. RESULTS: The findings indicated a significant difference between delinquent and non-delinquent juveniles with regard to family power structure, its subscales (P < 0.001), and identity style (P < 0.001). Moreover, the informational identity style was associated with lower levels of delinquency. In addition, a diffuse-evident identity style was related to the delinquency. CONCLUSIONS: These results emphasize that the inappropriate decision-making process pattern in a family has a significant effect on deviant behavior and identity style in adolescents. So, family power structure can be considered in therapeutic interventions (prevention and treatment) for adolescent delinquency. PMID- 26834796 TI - Applying Transtheoretical Model to Promote Physical Activities Among Women. AB - BACKGROUND: Physical activity is one of the most important indicators of health in communities but different studies conducted in the provinces of Iran showed that inactivity is prevalent, especially among women. OBJECTIVES: Inadequate regular physical activities among women, the importance of education in promoting the physical activities, and lack of studies on the women using transtheoretical model, persuaded us to conduct this study with the aim of determining the application of transtheoretical model in promoting the physical activities among women of Isfahan. MATERIALS AND METHODS: This research was a quasi-experimental study which was conducted on 141 women residing in Isfahan, Iran. They were randomly divided into case and control groups. In addition to the demographic information, their physical activities and the constructs of the transtheoretical model (stages of change, processes of change, decisional balance, and self efficacy) were measured at 3 time points; preintervention, 3 months, and 6 months after intervention. Finally, the obtained data were analyzed through t test and repeated measures ANOVA test using SPSS version 16. RESULTS: The results showed that education based on the transtheoretical model significantly increased physical activities in 2 aspects of intensive physical activities and walking, in the case group over the time. Also, a high percentage of people have shown progress during the stages of change, the mean of the constructs of processes of change, as well as pros and cons. On the whole, a significant difference was observed over the time in the case group (P < 0.01). CONCLUSIONS: This study showed that interventions based on the transtheoretical model can promote the physical activity behavior among women. PMID- 26834797 TI - Self-Immolation: The Literacy History Between India and Iran. PMID- 26834798 TI - Smoking and Its Related Factors Among Iranian High School Students. AB - BACKGROUND: In different studies, the prevalence of tobacco consumption has been growing in high schools boys. OBJECTIVES: This study was conducted to determine the prevalence of smoking and its related factors among Iranian high school students in 2011. MATERIALS AND METHODS: In this cross-sectional study, 450 male students from 15 high schools of Shahroud (northeast of Iran) were selected for evaluation of the knowledge, attitude and practices (KAP) of students regarding tobacco consumption. RESULTS: Overall, 51% (95% CI: 46.5 - 55.7) of the students had positive history of smoking for at least one time and 7.1% (95% CI: 5 - 10) of them were current smokers. The most prevalent source of information about smoking was TV and radio programs (48%) and friends were the second source (22%). Based on the students' opinions, entertainment and smoker friends were the most important reasons for smoking tendency. There was significant statistical association between students smoking and positive family history of smoking (P value < 0.05). CONCLUSIONS: The prevalence of smoking experince was very high among high school students. The most prevalent source of information about smoking was Iranian broadcasting companies. Positive family history of smoking and smoker friends were the important motivating factors toward smoking. PMID- 26834799 TI - Domestic Abuse in Behshahr, Iran. AB - BACKGROUND: The United Nations in a resolution defined abuse as any violent act that is primarily or exclusively committed against females and results in physical, sexual and psychological harm. OBJECTIVES: The aim of this research was to study the contributing factors of husband's violence against females residing in the city of Behshahr, Iran. MATERIALS AND METHODS: We distributed a specifically designed questionnaire among 380 married females aged between 15 and 65 years. According to the Morgan table, the subjects were randomly selected from a list of 301000 females. Demographic data and data on spouse abuse were then analyzed using the SPSS software, Spearman and Pearson correlation coefficients. According to Cronbach's alpha, the reliability of the questionnaire was 0.96. RESULTS: All of the females reported at least one form of violence within the past year, with R square 0.20, indicating that the independent variable can explain 20% of the violence against females. years of marriage, female's education, male's addiction and the number of children each had their share in the explanation of violence against females. CONCLUSIONS: This study revealed a high prevalence of domestic violence in the sample population. Violence existed among all ages, social categories and male occupational groups, and also involved both employed and unemployed females. The situation regarding domestic abuse is similar worldwide. PMID- 26834800 TI - Do Cancer Patients Prefer to Know the Diagnosis? A Descriptive Study Among Iranian Patients. AB - BACKGROUND: There are important differences regarding cancer disclosure in various geographical populations (Europeans, Western Asia, Eastern Asia), depending on multiple sociocultural factors, and therefore, there is no standard protocol on this issue, especially in Iran. OBJECTIVES: To evaluate the amount of information that Iranian patients have and their preference for the disclosure of the cancer diagnosis. PATIENTS AND METHODS: In this cross sectional descriptive research, patients admitted in the oncology departments of 3 referral medical centers, Imam Hussein, Shohada-e-Tajrish and Modarres, in Tehran, from March 2007 to April 2008, were questioned about their awareness and knowledge regarding their diagnosis. Two different structured questionnaires were designed for the people who know and who didn't know their diagnosis. For the former, the survey concerned their psychological reactions to their situations, whether they would prefer to know about their diagnosis and by whom they are preferred to be informed .For the latter, the questionnaire included their preference whether to know the diagnosis and their current emotional state. Descriptive statistics and chi square test was applied to analyze gathering Data, using SPSS version 14. RESULTS: 60.3% of the patients knew their diagnosis. Among the subjects who did not know their diagnosis, 88% preferred to be more informed about their diagnosis and 68% had some psychological reaction to their situations. Among the subjects who knew their diagnosis, 92.1 % preferred to know their diagnosis, 73.6% preferred to be informed directly by their physicians. Following the diagnostic disclosure, 81.5% reported that they had felt nervous, anxious and worried. CONCLUSIONS: The majority of Iranian patients with malignancy want to know the truth and they prefer to be informed directly by their doctors. PMID- 26834801 TI - Remission of Methamphetamine-Induced Withdrawal Delirium and Craving After Electroconvulsive Therapy. AB - INTRODUCTION: The aim of this study is to describe the use of electroconvulsive therapy (ECT) in the treatment of methamphetamine-induced withdrawal delirium and craving in a single case. CASE PRESENTATION: A 44-year-old male presented to the hospital in Fars province, Iran, with Methamphetamine-Induced Withdrawal Delirium who responded to ECT. CONCLUSIONS: The electroconvulsive therapy can be a suitable option for the treatment of methamphetamine withdrawal delirium and craving. Also, it can be usefully employed in these very serious conditions which may represent a risk to life. PMID- 26834802 TI - The Impact of Using Cell Phones After Light-Out on Sleep Quality, Headache, Tiredness, and Distractibility Among Students of a University in North of Iran. AB - BACKGROUND: Cell phone is a mere fascinating, as well as entertainment object and serves to keep young individuals in constant contact with their peers; and gives them a feeling of autonomy, identity and credibility. OBJECTIVES: Considering the increasing trend of using cell phones, the aim of the current study was to assess the extent to which the students of Mazandaran university of medical sciences use their phones after light-out, and to determine its relationship with sleep quality, headache, tiredness, and distractibility, after elimination of the impact of stressful events. MATERIALS AND METHODS: Overall, 358 students from different schools of the university participated in a cross-sectional study with self-report questionnaires (demographic questionnaire, cell phone use questionnaire, Pittsburgh sleep quality index, and social readjustment rating scale). Descriptive indices were used to express data, and the chi-square and logistic regression were used to interpret the results. RESULTS: Overall, 60% of the students used their cell phones after lights were out. There was a significant relationship between using cell phones late at night and insomnia, low energy, tiredness and headache. Once the impact of stressful events was eliminated, the relationship remained significant only for insomnia. No significant relationship was observed between using cell phones and distractibility. CONCLUSIONS: Students of Mazandaran university of medical sciences used their cell phones extensively after lights were out and the resulting insomnia may have affected their learning, as well as the quality of medical services provided by them. PMID- 26834803 TI - Child Abuse and Neglect Epidemiology in Secondary School Students of Yazd Province, Iran. AB - BACKGROUND: Child abuse is an issue that has many physical and psychological consequences. OBJECTIVES: This study was designed and conducted to investigate the current situation regarding child abuse, which can be used as a guideline for planning future interventions. MATERIALS AND METHODS: This was a descriptive, analytic cross-sectional study on 700 Yazd secondary school students in 2013, using a standardized self-administered questionnaire. The collected data was analyzed using the SPSS v.19 software and appropriate statistical tests and logistic regression analysis. P values of < 0.05 were considered statistically significant. RESULTS: Overall, 700 students (43%) were boys. Child abuse frequency was 93.5% (92.2% of boys and 94.4% of girls). The most common domains of child abuse among all students were neglect (83.8%), psychological (76.1%), physical (36.1%) and sexual (28.8 %), respectively. The most common domains of child abuse among female students were neglect (84.9%), psychological (82.3%), physical (32.5%) and sexual (31.5 %), and among male students, these were neglect (82.3%), psychological (67.9%), physical (41%) and sexual (25.3%). Demographic variables included substance abuse of parents, father's education, parents living status and having other jobs, which were significantly related variables to child abuse and neglect (P value < 0.05). CONCLUSIONS: Our study is the first investigation performed on patients with LCH and its possible association with EBV in Iran. Considering the P = 0.004, which is statistically significant, the findings do support the hypothesis of a possible role for EBV in the pathogenesis of LCH. These results are in accordance with several previous investigations, with positive findings. PMID- 26834804 TI - Emotional Intelligence and Depressive Symptoms as Predictors of Happiness Among Adolescents. AB - BACKGROUND: Given that happiness is an important construct to enable adolescents to cope better with difficulties and stress of life, it is necessary to advance our knowledge about the possible etiology of happiness in adolescents. OBJECTIVES: The present study sought to investigate the relationships of emotional intelligence, depressive symptoms, and happiness in a sample of male students in Tehran, Iran. MATERIALS AND METHODS: This cross-sectional study was conducted on a sample of high school students in Tehran in 2012. The participants comprised of 188 male students (aged 16 to 19 years old) selected by multi-stage cluster sampling method. For gathering the data, the students filled out assessing emotions scale, Beck depression inventory-II, and Oxford happiness inventory. Data analysis was carried out using descriptive and analytical statistics in statistical package for social sciences (SPSS) software. RESULTS: The findings showed that a significant positive association existed between high ability of emotional intelligence and happiness (P < 0.01). Conversely, the low ability of emotional intelligence was associated with unhappiness (P < 0.01), there was a positive association between non-depression symptoms and happiness (P < 0.05), and severe depressive symptoms were positively associated with unhappiness (P < 0.01). High ability of emotional intelligence (P < 0.01) and non depression symptoms (P < 0.05) were the strongest predictors of happiness. CONCLUSIONS: These findings reinforced the importance of emotional intelligence as a facilitating factor for happiness in adolescences. In addition, the findings suggested that depression symptoms may be harmful for happiness in adolescents. PMID- 26834805 TI - Comparing the Effects of Self-Controlled and Examiner-Controlled Feedback on Learning in Children With Developmental Coordination Disorder. AB - BACKGROUND: Feedback can improve task learning in children with developmental coordination disorder (DCD). However, the frequency and type of feedback may play different role in learning and needs to more investigations. OBJECTIVES: The aim of this study was to evaluate the acquisition and retention of new feedback skills in children with DCD under different frequency of self-control and control examiner feedback. MATERIALS AND METHODS: In this quasi-experimental study with pretest-posttest design, participants based on their retention were divided into four feedback groups: self-controlled feedback groups with frequencies of 50% and75%, experimenter controls with frequencies of 50% and 75%. The study sample consisted of 24 boys with DCD aged between 9 to 11 years old in Ahvaz City, Iran. Then subjects practiced 30 throwing (6 blocks of 5 attempts) in eighth session. Acquisition test immediately after the last training session, and then the retention test were taken. Data were analyzed using the paired t-test, ANOVA and Tukey tests. RESULTS: The results showed no significant difference between groups in the acquisition phase (P > 0.05). However,in the retention session, group of self-control showed better performance than the control tester group (P < 0.05). CONCLUSIONS: Based on the current findings, self-control feedback with high frequency leads to more learning in DCD children. The results of this study can be used in rehabilitation programs to improve performance and learning in children with DCD. PMID- 26834806 TI - Study of the Types of Domestic Violence Committed Against Women Referred to the Legal Medical Organization in Urmia - Iran. AB - BACKGROUND: Today, domestic violence against women is a growing epidemic that can be observed in many countries. OBJECTIVES: This study was carried out to determine the types of domestic violence against women who were referred to the Legal Medical Organization of Iran in Urmia, Iran in 2012. MATERIALS AND METHODS: The descriptive survey included demographic information, abuse screening, and items regarding partner involvement. Data was gathered using face-to-face structured interviews. The study population included 300, women 18 years of age or older, and data was collected about their demographic characteristics and the types of domestic violence they experienced. SPSS software version 16 was used for the analyses. RESULTS: The majority of participants were in the 25 - 30 age group, and 83% of them were battered by their husbands in various ways. No significant relationships were observed between violence and unemployment, increasing age, and home ownership. CONCLUSIONS: The prevalence of abuse reported by women in this population suggests that many women that are referred to the Legal Medical Organization of Iran may have a history of abuse. Abused women may have different reasons for seeking a divorce. If routine screening for abuse is included in counseling, health providers will have the opportunity to develop a safety plan and initiate appropriate referrals. PMID- 26834807 TI - The Relationship Between Marital Satisfaction and Compatibility With Type 2 Diabetes. AB - BACKGROUND: Marriage is a legal pact between a man and a woman for participating in a social life together which can play an important role in dealing with difficulties. OBJECTIVES: This study was carried out to investigate the relationship between marital satisfaction and compatibility with diabetes in patients with type 2 diabetes. PATIENTS AND METHODS: The study method was descriptive-correctional. The study sample included 160 diabetic patients (103 females and 57 males) who were randomly selected. The instruments used were Enrich marital satisfaction questionnaire and the questionnaire of compatibility with diabetes. In addition, the data were analyzed through descriptive statistics and analysis of variance by SPSS. RESULTS: The result of the study revealed a significant correlation (P = 0.006) between marital satisfaction and compatibility with diabetes in women with type 2 diabetes (r = 0.26). However, this correlation was not significant in men with diabetes. Also, a significant relationship existed between the dimensions of compatibility with diabetes and marital satisfaction in both men and women with diabetes. CONCLUSIONS: Marital satisfaction affects compatibility with diabetes in women. Therefore, it might be possible to increase compatibility with diabetes in them by offering specialized interventions as family and couples therapies and giving consultations. PMID- 26834808 TI - Assessing Negative Automatic Thoughts: Psychometric Properties of the Turkish Version of the Cognition Checklist. AB - BACKGROUND: Beck's theory of emotional disorder suggests that negative automatic thoughts (NATs) and the underlying schemata affect one's way of interpreting situations and result in maladaptive coping strategies. Depending on their content and meaning, NATs are associated with specific emotions, and since they are usually quite brief, patients are often more aware of the emotion they feel. This relationship between cognition and emotion, therefore, is thought to form the background of the cognitive content specificity hypothesis. Researchers focusing on this hypothesis have suggested that instruments like the cognition checklist (CCL) might be an alternative to make a diagnostic distinction between depression and anxiety. OBJECTIVES: The aim of the present study was to assess the psychometric properties of the Turkish version of the CCL in a psychiatric outpatient sample. PATIENTS AND METHODS: A total of 425 psychiatric outpatients 18 years of age and older were recruited. After a structured diagnostic interview, the participants completed the hospital anxiety depression scale (HADS), the automatic thoughts questionnaire (ATQ), and the CCL. An exploratory factor analysis was performed, followed by an oblique rotation. The internal consistency, test-retest reliability, and concurrent and discriminant validity analyses were undertaken. RESULTS: The internal consistency of the CCL was excellent (Cronbach's alpha = 0.95). The test-retest correlation coefficients were satisfactory (r = 0.80, P < 0.001 for CCL-D, and r = 0.79, P < 0.001 for CCL A). The exploratory factor analysis revealed that a two-factor solution best fit the data. This bidimensional factor structure explained 51.27 % of the variance of the scale. The first factor consisted of items related to anxious cognitions, and the second factor of depressive cognitions. The CCL subscales significantly correlated with the ATQ (rs 0.44 for the CCL-D, and 0.32 for the CCL-A) as well as the other measures of mood severity (all Ps < 0.01). To a great extent, all items of the CCL were able to distinguish the clinical and non-clinical groups, suggesting the scale has high discriminating validity. CONCLUSIONS: The current study has provided evidence that the Turkish version of the CCL is a reliable and valid instrument to assess NATs in a clinical outpatient sample. PMID- 26834809 TI - The Effect of Beck's Cognitive Therapy and Mindfulness-Based Cognitive Therapy on Sociotropic and Autonomous Personality Styles in Patients With Depression. AB - BACKGROUND: Depression is characterized by a great risk of relapse and recurrence. Mindfulness-based cognitive therapy (MBCT) and cognitive therapy are efficacious psychosocial interventions for recurrent depression. OBJECTIVES: The aim of the present research was to compare the effect of Beck's cognitive therapy (BCT) and MBCT on reduction of depression and sociotropic and autonomous personality styles in Iranian depressed patients. PATIENTS AND METHODS: The study sample consisted of 30 subjects randomly selected from patients with depression in Mashhad city, Iran. The subjects were assigned randomly to experimental groups. The 2 techniques used for treatment were BCT and MBCT. The data collection instruments used in the research consisted of psychological interview, the Beck Depression Inventory II and the revised Personal Style Inventory (RPSI). The research data was analyzed using repeated measures analysis of variance (ANOVA). RESULTS: BCT and MBCT were effective in reducing depression, but BCT and MBCT did not cause any change in the sociotropic and autonomous personality styles in patients with depression. CONCLUSIONS: The results provide support for the role of BCT and MBCT plays in reducing depression. However, the results did not approve their role in changing sociotropic and autonomous personality styles in patients with depression. PMID- 26834810 TI - Procrastination and Self-Efficacy Among Intravenous Drug Users on a Methadone Maintenance Program in Sari City, Iran, 2013. AB - BACKGROUND: Self-efficacy is the belief that one has the ability to implement the behaviors needed to produce a desired effect. There has been growing interest in the role of self-efficacy as a predictor and/or mediator of treatment outcome in a number of domains. Procrastination is a self-regulatory failure, defined as the voluntary delay of an intended course of action despite expecting to be worse off for the delay. Behavioral procrastination is a self-sabotage strategy that allows people to shift blame and avoid action; the decisional procrastination strategy is to put off making a decision when dealing with conflicts or choices. Procrastination has a great role in quitting drug addiction. OBJECTIVES: The aim of this study was to determine the relationship between procrastination and self efficacy and other factors among intravenous drug users. PATIENTS AND METHODS: This cross-sectional study was conducted on 178 intravenous drug users in the behavioral disease counseling, health center in Sari city, Mazandaran province, Iran, in 2013. The samples were selected through census sampling, descriptive and inferential statistics were used to measure the properties of distribution that depicts a set of data shown as frequency distribution tables, while for the mean and standard deviation, chi-square, Fisher and Spearman-Brown coefficients were used to analyze the data. RESULTS: The mean age of the participants was 43 years. Seventy-two percent of them were married and opium was the first drug used. The first substance used in them was 54% of opium, 33% cannabis and 5% alcohol and 79% smoking. The reason of the first drug use in 32% of the subjects was temptation and in 10% a friend's influence. The mean age of the first drug use was 23 years, and the frequency was 2 times per day. All of them had relapse at least once. Seven percent of them currently use other materials (2% crystal, 5% alcohol and opium and crack) both in methadone treatment. Behavioral procrastination in 60.5% of them and decisional procrastination in 62% is from low to average range. There was a significant relationship between relapse and self-efficacy as well as between self-efficacy and the age of the first drug use, drug dose, and procrastination for treatment, marriage, employment and job. Also, the relationship between behavioral procrastination and self-efficacy was significant and inverse. CONCLUSIONS: This study found a significant difference between procrastination and self-efficacy as well as other related factors. It is important to include drug users and the society organizations representing them in every stage of the governmental policy and program development process to make them responsive to the needs of the community. PMID- 26834811 TI - Difficulties in Emotion Regulation and Mindfulness in Psychological and Somatic Symptoms of Functional Gastrointestinal Disorders. AB - BACKGROUND: Negative emotions are the best predictors for psychological and physical health. OBJECTIVES: We aimed to investigate the role of difficulties in emotion regulation and mindfulness on psychological and somatic symptoms of patients with functional gastrointestinal disorders (FGID). PATIENTS AND METHODS: In this cross-sectional study, the studied sample was selected using census method. A total of 167 patients with FGID completed a demographic questionnaire, difficulties in emotion regulation scale (DERS), mindful attention awareness scale (MAAS), depression, anxiety and stress scale (DASS), and gastrointestinal symptom rating scale (GSRS). To examine the relationship between studied variables, Pearson correlation coefficients and multiple regression analyses were used. RESULTS: The findings of the study indicate that difficulties in emotion regulation and mindfulness are significantly correlated to both increased psychological and somatic symptoms. Some factors of difficulties in emotion regulation positively predicted those symptoms. Among these factors, only lack of awareness was not significantly correlated with both symptoms as well as decreased mindfulness. CONCLUSIONS: The findings suggest some potential targets to reduce symptoms. Patients with FGID may benefit from treatments that facilitate emotional experience, functional status, and ability to control impulsive behaviors and behave according to the goals when experiencing negative emotions. PMID- 26834812 TI - Mini-open PLIF for Moderate to High Grade Spondylolisthesis: Technique to Achieve Spontaneous Reduction. AB - OBJECTIVE: The purpose of this study was to evaluate the surgical technique and outcome of mini-open posterior lumbar interbody fusion (PLIF) under circumferential releasing technique. METHODS: Fourty patients who underwent mini open PLIF using the percutaneous screw fixation system for Meyerding Grade II spondylolisthesis or more were retrospectively studied. After complete circumferential release, the slipped vertebrae would tend to obtain spontaneous reduction, and with compressive force by percutaneous screw fixation, additional reduction could be achieved. The radiological measurements including slippage reduction, disc height, restoration of lumbar lordotic angle and focal segmental angle were analyzed. The clinical outcome was assessed using the visual analog scale (VAS) and low back outcome score (LBOS), and procedure related complications were also analyzed. RESULTS: Slippage percentage was improved from 38.0+/-12.6% to 9.3+/-7.8% and lumbar lordotic angle was changed from 43.0+/-13.8 degrees to 48.2+/-10.3 degrees . Focal segmental angle improved from 10.1+/-8.5 degrees to 15.9+/-6.0 degrees . The mean LBOS and mean pain score were also improved significantly. Complications included one case of medial penetration of pedicle border and two cases of transient radiculopathy. However, there were no signs of neurological aggravation or fusion failure during the follow-up period. CONCLUSION: Mini-open PLIF using the percutaneous screw fixation following complete circumferential release can be safe and effective treatment for even moderate to severe grade spondylolisthesis. PMID- 26834813 TI - Combined Interlaminar and Paraisthmic Approach for Co-existing Intracanal and Foraminal Lesion. AB - OBJECTIVE: Stenosis or herniated nucleus pulposus (HNP) occupying lumbar intracanal and foraminal area is an important cause of double radicular symptoms. Using the combined interlaminar and paraisthmic approach, we performed decompression surgery in patients with co-existing intracanal and foraminal lesions. The objective of this study is to describe usefulness and outcome of combined interlaminar and paraisthmic approach surgery and to analysis the cause of poor outcome. METHODS: Between Apr 2009 and Apr 2014, 78 patients (42 males and 36 females) with intracanal and foraminal lesions were enrolled in this study. Patients with a vacuum disc, spondylolisthesis, instability or an isthmic defect on the preoperative dynamic view radiograph were excluded from this study. All patients underwent surgery through a combined approach for discectomy and decompression. The outcome of surgery was evaluated and classified into excellent, good, fair and poor. RESULTS: The results were excellent in 53 patients, good in 9, fair in 6 and poor in 10 during the follow-up. The outcome of the combined approach was excellent to fair in 87% (68 of 78) patients in our study. In the poor outcome group, three patients complained of early-onset relapsed pain (<1 month) and another seven patients complained of delayed-onset pain (>3 months). CONCLUSION: Combined approach for both intracanal and foraminal area lesions may be useful if selectively performed on patients whose facet joint is relatively intact, and that it is worthy of consideration as an alternative to fusion surgery; however, further studies are needed. PMID- 26834814 TI - Predictors of Outcome in Patients with Cervical Spondylotic Myelopathy Undergoing Unilateral Open-Door Laminoplasty. AB - OBJECTIVE: This study aimed to analyze prognostic factors affecting surgical outcomes of expansive laminoplasty for cervical spondylotic myelopathy (CSM). METHODS: Using the Frankel scale and Japanese Orthopaedic Association (JOA) scale, we retrospectively reviewed the outcomes of 45 consecutive patients who underwent modified unilateral open-door laminoplasty using hydroxyapatite spacers and malleable titanium miniplates between June 2008 and May 2014. The patients were assigned to the good and poor clinical outcome groups, with good outcome defined as a JOA recovery rate >75%. RESULTS: The mean preoperative JOA scale was significantly higher in the good outcome group (14.95+/-3.21 vs. 10.78+/-6.07, p<0.001), whereas the preoperative cervical range of motion (ROM) in this group was significantly lower (29.89 degrees +/-10.11 vs. 44.35 degrees +/- 8.88, p<0.001). In univariate analysis, a high preoperative JOA scale (odds ratio (OR) 1.271, 95% confidence interval (CI) 1.005-1.607) and low preoperative cervical ROM(OR 0.858, 95% CI 0.786-0.936) were statistically correlated with good outcomes. Furthermore, these factors demonstrated an independent association with clinical outcomes (preoperative JOA scale: OR 1.344, 95% CI 1.019-1.774, p=0.036; preoperative cervical ROM: OR 0.860, 95% CI 0.788-0.940, p=0.001). CONCLUSION: In this study, a high preoperative JOA scale was associated with good clinical outcome after laminoplasty, whereas a higher preoperative cervical spine ROM was associated with poor clinical outcome. This may suggests that cervical mobility and preoperative neurological status affect clinical outcomes of laminoplasty. PMID- 26834815 TI - Minimally Invasive Extraforaminal Lumbar Interbody Fusion for Revision Surgery: A Technique through Kambin's Triangle. AB - OBJECTIVE: The purpose of this study was to evaluate the clinical outcomes of minimally invasive extraforaminal lumbar interbody fusion (ELIF) for revision surgery. METHODS: From January 2011 to December 2012, 12 patients who underwent minimally invasive ELIF through the Kambin's triangle for revision surgery were included in this study. All patients underwent the surgical procedure in the following sequence: (1) epidural anesthesia, (2) exposing the Kambin's triangle toward the lateral part of the dura (partial resection of the superior articular process), (3) bilateral cage insertion for reinforcement of stabilization and fusion, and (4) percutaneous transpedicular screwing. Clinical outcomes were assessed using the visual analogue scale (VAS), and Oswestry disability index (ODI). Imaging and clinical findings including surgical techniques, clinical outcomes, and related complications were depicted and analyzed. RESULTS: The mean age of the patients (5 men, 7 women) was 60.7+/-13.4 years, and the mean follow up period was 27.1+/-4.9 months. The mean VAS (back and leg) score improved significantly at final follow-up. The mean ODI score decreased as follows: preoperative, 76.78+/-6.08; 3 months after the surgery, 37.74+/-6.67; and at final follow-up, 29.91+/-2.98. Two patients presented with transient nerve root irritation, but there were no cases of incidental dural tear or serious infection. No significant neurological deterioration or major complication was noted in any of the patients. CONCLUSION: Minimally invasive ELIF for revision surgery is an effective surgical option with a low complication rate. PMID- 26834816 TI - Cauda Equina Syndrome Caused by Idiopathic Epidural Lipomatosis. AB - Spinal epidural lipomatosis (SEL) is a rare condition that presents as a back pain with progressive neurologic symptoms. Most affected patients are obese and receiving steroid therapy, or have an endocrinopathies. We report a rare case of cauda equina syndrome caused by SEL in a non-obese healthy young man without any evident traumatic episode. A healthy 19-year-old man, who had experienced lower back pain for two months, visited our emergency room because of the sudden development of motor weakness and voiding difficulty. Lumbar magnetic resonance image revealed extradural fat compressing the cauda equina. Urgent decompression via posterior laminectomy and excision of excess epidural fat resulted in an immediate symptom improvement. PMID- 26834817 TI - Cervical Spine Chondroma Compressing Spinal Cord: A Case Report and Literature Review. AB - Chondromas are benign tumor of cartilaginous tissue that is rarely found in spine. The authors document a rare case of a 72 year old male patient with a cervical spinal chondroma compressing the spinal cord. The patient had symptoms of motor and sensory deficits, dysphagia and dysarthria. C1 and C2 laminotomy was done and the spinal tumor was removed. The patient gradually recovered from his previous symptom after the surgery. PMID- 26834818 TI - Idiopathic Spontaneous Intramedullary Hemorrhage: A Report of a Rare Case of Repeated Intramedullary Hemorrhage with Unknown Etiology. AB - A 48-year-old woman presented with acute voiding difficulty, numbness and weakness of both lower extremities. Magnetic resonance imaging (MRI) showed an intramedullary hemorrhagic mass that extended from T9 to T10. T8-T10 laminotomy and surgical removal of the hemorrhagic mass was performed. The pathological diagnosis was hematoma. Her neurological status remained the same after the operation. At 5 days post-operation, the patient suddenly became paraplegic, and MRI that was immediately performed revealed a recurrent intramedullary hemorrhage. Emergent surgical evacuation was performed. Again, histological examination showed only hematoma, without any evidence of abnormal vessels or a tumor. A postoperative MRI revealed no abnormal lesions other than those resulting from postoperative changes. At a 9-month follow up, the patient could walk a short distance with the aid of a walker. Because spontaneous intramedullary hemorrhage with unknown etiology is very rare, it is essential to perform a meticulous inspection of the hemorrhagic site to find the underlying cause. Repeated hemorrhage can occur; therefore, close observation of patients after surgery is important in cases without an apparent etiology. Urgent surgical evacuation is important to improve outcomes in these cases. PMID- 26834819 TI - Plasmacytoma to the Axis Mimicking Metastatic Paraganglioma: Circumferential Reconstruction via Posterior Approach. AB - Plasmacytoma is a malignant plasma cell tumor growing within soft tissue or the axial skeleton. Here, we present the case of a patient with plasmacytoma of the axis vertebra who underwent decompressive surgery with reconstruction via a posterior approach. The patient was referred because of quadriparesis with severe neck pain. Magnetic resonance imaging revealed a relatively demarcated, highly enhanced mass lesion in a destructed axis, with spinal cord compression. Computed tomography revealed a 5.6*4.3 cm adrenal mass at the left retroperitoneal space. We suspected the axis lesion to be a metastatic paraganglioma from the adrenal mass. The patient underwent total excision of the tumor under an operative microscope with occipitocervical fixation. Histopathologically, the tumor was shown to be a plasmacytoma. Following the operation, the patient recovered without significant complications. This was a rare case of plasmacytoma in the axis, mimicking metastatic paraganglioma. PMID- 26834820 TI - Fully Endoscopic Interlaminar Detethering of Spinal Cord in Tethered Cord Syndrome: A Case Report and Technical Description. AB - A 19-year-old man presented with long lasting significant back and bilateral leg pain, and hypoesthesia on the lateral side of both his thighs for which he had undergone several courses of medication and bouts of physical therapy treatment. His urodynamic parameters were normal and lumbar magnetic resonance imaging (MRI) revealed a low-lying conus at the L2-3 level with a thickened fatty filum, and he was diagnosed as having tethered cord syndrome (TCS). The patient underwent a fully endoscopic detethering through an interlaminar approach with intraoperative neurophysiological monitoring. The thickened filum terminale was located and then the filum was coagulated and cut. The patient showed a significant improvement in his preoperative symptoms, and reported no problems at 2-year follow-up. Detethering of the spinal cord in tethered cord syndrome using a fully endoscopic interlaminar approach provides the advantages of minimal damage to tissues, less postoperative discomfort, early postoperative recovery, and a shorter hospitalization. PMID- 26834821 TI - Physician perception regarding side-effect profile at the onset of antidepressant treatment: a survey of Israeli psychiatrists and primary care physicians. AB - BACKGROUND: One of the major factors affecting treatment compliance and outcome in patients is the wide range of side effects (SEs) associated with antidepressants. In the present study, we aimed to assess the extent to which Israeli primary care (PC) physicians and psychiatrists discuss the SEs of selective serotonin reuptake inhibitors (SSRIs) with patients prior to the onset of treatment. METHODS: A cross-sectional questionnaire survey was conducted among PC physicians (N = 123) and psychiatrists (N = 105). Questionnaires were distributed using a mixed-modality design, combining a web survey and in-person delivery of questionnaires. RESULTS: A significant percentage of our respondents reported that they rarely discuss psychological (60 %) or severe (29 %) SEs of SSRIs. Nearly half (41 %) admitted to avoiding discussion of impact on suicidal ideation. Specialists were noted to discuss and evaluate SEs significantly more than residents, and Psychiatrists more than PC physicians. Specifically, psychiatrists more often discussed the possibility of sexual dysfunction (t (225) = 2.23; p < 0.05) and suicidal ideation (t (225) = 2.11; p < 0.05). CONCLUSIONS: It seems that PC physicians and psychiatrists surveyed in this study do not share sufficient information regarding the SEs of SSRIs with their patients at the onset of treatment. In improving this practice, the integration of proper SE management into educational interventions has potential in enhancing compliance and improving expertise and level of care. PMID- 26834822 TI - Terrestrial 3D laser scanning to track the increase in canopy height of both monocot and dicot crop species under field conditions. AB - BACKGROUND: Plant growth is a good indicator of crop performance and can be measured by different methods and on different spatial and temporal scales. In this study, we measured the canopy height growth of maize (Zea mays), soybean (Glycine max) and wheat (Triticum aestivum) under field conditions by terrestrial laser scanning (TLS). We tested the hypotheses whether such measurements are capable to elucidate (1) differences in architecture that exist between genotypes; (2) genotypic differences between canopy height growth during the season and (3) short-term growth fluctuations (within 24 h), which could e.g. indicate responses to rapidly fluctuating environmental conditions. The canopies were scanned with a commercially available 3D laser scanner and canopy height growth over time was analyzed with a novel and simple approach using spherical targets with fixed positions during the whole season. This way, a high precision of the measurement was obtained allowing for comparison of canopy parameters (e.g. canopy height growth) at subsequent time points. RESULTS: Three filtering approaches for canopy height calculation from TLS were evaluated and the most suitable approach was used for the subsequent analyses. For wheat, high coefficients of determination (R(2)) of the linear regression between manually measured and TLS-derived canopy height were achieved. The temporal resolution that can be achieved with our approach depends on the scanned crop. For maize, a temporal resolution of several hours can be achieved, whereas soybean is ideally scanned only once per day, after leaves have reached their most horizontal orientation. Additionally, we could show for maize that plant architectural traits are potentially detectable with our method. CONCLUSIONS: The TLS approach presented here allows for measuring canopy height growth of different crops under field conditions with a high temporal resolution, depending on crop species. This method will enable advances in automated phenotyping for breeding and precision agriculture applications. In future studies, the TLS method can be readily applied to detect the effects of plant stresses such as drought, limited nutrient availability or compacted soil on different genotypes or on spatial variance in fields. PMID- 26834823 TI - Evolution of sexual reproduction: a view from the Fungal Kingdom supports an evolutionary epoch with sex before sexes. AB - Sexual reproduction is conserved throughout each supergroup within the eukaryotic tree of life, and therefore thought to have evolved once and to have been present in the last eukaryotic common ancestor (LECA). Given the antiquity of sex, there are features of sexual reproduction that are ancient and ancestral, and thus shared in diverse extant organisms. On the other hand, the vast evolutionary distance that separates any given extant species from the LECA necessarily implies that other features of sex will be derived. While most types of sex we are familiar with involve two opposite sexes or mating types, recent studies in the fungal kingdom have revealed novel and unusual patterns of sexual reproduction, including unisexual reproduction. In this mode of reproduction a single mating type can on its own undergo self-fertile/homothallic reproduction, either with itself or with other members of the population of the same mating type. Unisexual reproduction has arisen independently as a derived feature in several different lineages. That a myriad of different types of sex determination and sex determinants abound in animals, plants, protists, and fungi suggests that sex specification itself may not be ancestral and instead may be a derived trait. If so, then the original form of sexual reproduction may have been unisexual, onto which sexes were superimposed as a later feature. In this model, unisexual reproduction is both an ancestral and a derived trait. In this review, we consider what is new and what is old about sexual reproduction from the unique vantage point of the fungal kingdom. PMID- 26834825 TI - Tyrosinase inhibitory activity of flavonoids from Artocarpus heterophyllous. AB - BACKGROUND: Tyrosinase is an oxidoreductase that is very important in medicine and cosmetics because the excessive production of melanin causes hyperpigmentation. The development of novel, effective tyrosinase inhibitors has long been pursued. In preliminary tests, we found that an extract of the wood of Artocarpus heterophyllous (AH) potently inhibited tyrosinase activity. RESULTS: Two new flavonoids, artocaepin E (1) and artocaepin F (2), were isolated from the wood of AH, together with norartocarpetin (3), artocarpanone (4), liquiritigenin (5), steppogenin (6), and dihydromorin (7). Their structures were elucidated using one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and mass spectrometry. The absolute configuration of 2 was determined from the circular dichroism (CD) spectrum. Artocarpanone (4) had the most potent tyrosinase inhibitory effect, with an IC50 of 2.0 +/- 0.1 MUM, followed by artocaepin E (1) and steppogenin (6), with IC50 values of 6.7 +/- 0.8 and 7.5 +/- 0.5 MUM, respectively. A kinetic investigation indicated that 1 showed competitive inhibition, with an inhibition constant (K i) of 6.23 MUM. CONCLUSIONS: These results demonstrate that extracts of the wood of AH and its phytochemical constituents are potential sources for skin-whitening agents.Graphical abstractArtocarmin E (1) and artocarmin F (2) were isolated from the wood of Artocarpus heterophyllous. Their structures were elucidated using nuclear magnetic resonance analysis and mass spectrometric methods. PMID- 26834826 TI - Harnessing natural selection to tackle the problem of prey naivete. AB - Many populations are threatened or endangered because of excessive predation resulting from individuals' inability to recognize, avoid, or escape alien predators. Such prey naivete is often attributed to the absence of prior experience and co-evolution between native prey and introduced predators. Many reintroduction programs focus on reducing predation rate by excluding introduced predators, a focus which ignores, and indeed exacerbates, the problem of prey naivete. We argue for a new paradigm in reintroduction biology that expands the focus from predator control to kick-starting learning and evolutionary processes between alien predators and reintroduced prey. By exposing reintroduced prey to carefully controlled levels of alien predators, in situ predation could enhance reintroduction success by facilitating acquisition of learned antipredator responses and through natural selection for appropriate antipredator traits. This in situ predator exposure should be viewed as a long-term process but is likely to be the most efficient and expedient way to improve prey responses and assist in broadscale recovery of threatened species. PMID- 26834824 TI - Chinese herbal medicines as a source of molecules with anti-enterovirus 71 activity. AB - Enterovirus 71 (EV71) is one of the causative agents of hand, foot, and mouth disease (HFMD), which sometimes leads to severe neurological disease and death in the Asia-Pacific region. In Chinese medicine, HFMD is caused mainly by an accumulation of damp-heat and toxicity in the body. No effective drugs are currently available for the treatment and prevention of EV71 infection. This review summarizes the potential Chinese herbal extracts and isolated compounds with antiviral activity against EV71 and their clinical applications, especially those categorized as heat-clearing and detoxifying. PMID- 26834827 TI - Mothers and not genes determine inherited differences in cadmium sensitivities within unexposed populations of the freshwater crustacean Gammarus fossarum. AB - Deciphering evolutionary processes occurring within contaminated populations is important for the ecological risk assessment of toxic chemicals. Whereas increased tolerance to contaminants is well documented in aquatic animal populations, whether such phenotypic changes occur through genetic adaptation is still debated. In that sense, several studies with the freshwater crustacean Gammarus concluded in a weak potential for genetic adaptation to cadmium (Cd), while others reported inheritable increased tolerance in Cd-contaminated populations. Using quantitative genetics and selection experiments, this study sought to further assess the potential of Gammarus populations to genetically adapt to Cd. By combining the control of the reproductive cycle of this species in the laboratory and protocols of individual Cd exposure, we conducted half-sib analyses to establish the genetic and environmental sources of variance in Cd sensitivity of neonates. Prior to experiments, computations allowed optimizing the experimental design in order to increase the power to detect additive genetic variance. The main findings are the existence of strong between-brood variability along with weak heritability of Cd sensitivity within Gammarus populations. This study also revealed a significant maternal effect on individual Cd sensitivity. This sheds new light on the importance of maternal influence in microevolutionary processes occurring in contaminated environments. PMID- 26834828 TI - One health - an ecological and evolutionary framework for tackling Neglected Zoonotic Diseases. AB - Understanding the complex population biology and transmission ecology of multihost parasites has been declared as one of the major challenges of biomedical sciences for the 21st century and the Neglected Zoonotic Diseases (NZDs) are perhaps the most neglected of all the Neglected Tropical Diseases (NTDs). Here we consider how multihost parasite transmission and evolutionary dynamics may affect the success of human and animal disease control programmes, particularly neglected diseases of the developing world. We review the different types of zoonotic interactions that occur, both ecological and evolutionary, their potential relevance for current human control activities, and make suggestions for the development of an empirical evidence base and theoretical framework to better understand and predict the outcome of such interactions. In particular, we consider whether preventive chemotherapy, the current mainstay of NTD control, can be successful without a One Health approach. Transmission within and between animal reservoirs and humans can have important ecological and evolutionary consequences, driving the evolution and establishment of drug resistance, as well as providing selective pressures for spill-over, host switching, hybridizations and introgressions between animal and human parasites. Our aim here is to highlight the importance of both elucidating disease ecology, including identifying key hosts and tailoring control effort accordingly, and understanding parasite evolution, such as precisely how infectious agents may respond and adapt to anthropogenic change. Both elements are essential if we are to alleviate disease risks from NZDs in humans, domestic animals and wildlife. PMID- 26834830 TI - Assessing early fitness consequences of exotic gene flow in the wild: a field study with Iberian pine relicts. AB - Gene flow from plantations of nonlocal (genetically exotic) tree provenances into natural stands of the same species is probably a widespread phenomenon, but its effects remain largely unexamined. We investigated early fitness consequences of intraspecific exotic gene flow in the wild by assessing differences in survival among native, nonlocal, and F1 intraspecific hybrid seedlings naturally established within two native pine relicts (one of Pinus pinaster and the other of P. sylvestris) surrounded by nonlocal plantations. We obtained broad-scale temporally sequential genotypic samples of a cohort of recruits in each pine relict, from seeds before dispersal to established seedlings months after emergence, tracking temporal changes in the estimated proportion of each parental cross-type. Results show significant proportions of exotic male gametes before seed dispersal in the two pine relicts. Subsequently to seedling establishment, the frequency of exotic male gametes became nonsignificant in P. pinaster, and dropped by half in P. sylvestris. Exotic zygotic gene flow was significantly different from zero among early recruits for P. sylvestris, decreasing throughout seedling establishment. Seedling mortality resulted in small late sample sizes, and temporal differences in exotic gene flow estimates were not significant, so we could not reject the null hypothesis of invariant early viability across parental cross types in the wild. PMID- 26834829 TI - Potential drivers of virulence evolution in aquaculture. AB - Infectious diseases are economically detrimental to aquaculture, and with continued expansion and intensification of aquaculture, the importance of managing infectious diseases will likely increase in the future. Here, we use evolution of virulence theory, along with examples, to identify aquaculture practices that might lead to the evolution of increased pathogen virulence. We identify eight practices common in aquaculture that theory predicts may favor evolution toward higher pathogen virulence. Four are related to intensive aquaculture operations, and four others are related specifically to infectious disease control. Our intention is to make aquaculture managers aware of these risks, such that with increased vigilance, they might be able to detect and prevent the emergence and spread of increasingly troublesome pathogen strains in the future. PMID- 26834831 TI - Whole genome sequencing shows sleeping sickness relapse is due to parasite regrowth and not reinfection. AB - The trypanosome Trypanosoma brucei gambiense (Tbg) is a cause of human African trypanosomiasis (HAT) endemic to many parts of sub-Saharan Africa. The disease is almost invariably fatal if untreated and there is no vaccine, which makes monitoring and managing drug resistance highly relevant. A recent study of HAT cases from the Democratic Republic of the Congo reported a high incidence of relapses in patients treated with melarsoprol. Of the 19 Tbg strains isolated from patients enrolled in this study, four pairs were obtained from the same patient before treatment and after relapse. We used whole genome sequencing to investigate whether these patients were infected with a new strain, or if the original strain had regrown to pathogenic levels. Clustering analysis of 5938 single nucleotide polymorphisms supports the hypothesis of regrowth of the original strain, as we found that strains isolated before and after treatment from the same patient were more similar to each other than to other isolates. We also identified 23 novel genes that could affect melarsoprol sensitivity, representing a promising new set of targets for future functional studies. This work exemplifies the utility of using evolutionary approaches to provide novel insights and tools for disease control. PMID- 26834832 TI - Fish population genetic structure shaped by hydroelectric power plants in the upper Rhine catchment. AB - The Rhine catchment in Switzerland has been transformed by a chain of hydroelectric power stations. We addressed the impact of fragmentation on the genetic structure of fish populations by focusing on the European chub (Squalius cephalus). This fish species is not stocked and copes well with altered habitats, enabling an assessment of the effects of fragmentation per se. Using microsatellites, we genotyped 2133 chub from 47 sites within the catchment fragmented by 37 hydroelectric power stations, two weirs and the Rhine Falls. The shallow genetic population structure reflected drainage topology and was affected significantly by barriers to migration. The effect of power stations equipped with fishpasses on genetic differentiation was detectable, albeit weaker than that of man-made barriers without fishpasses. The Rhine Falls as the only long standing natural obstacle (formed 14 000 to 17 000 years ago) also had a strong effect. Man-made barriers also exacerbated the upstream decrease in allelic diversity in the catchment, particularly when lacking fishpasses. Thus, existing fishpasses do have the desired effect of mitigating fragmentation, but barriers still reduce population connectivity in a fish that traverses fishpasses better than many other species. Less mobile species are likely to be affected more severely. PMID- 26834833 TI - Adaptation of lodgepole pine and interior spruce to climate: implications for reforestation in a warming world. AB - We investigated adaptation to climate in populations of two widespread tree species across a range of contrasting environments in western Canada. In a series of common garden experiments, bud phenology, cold hardiness, and seedling growth traits were assessed for 254 populations in the interior spruce complex (Picea glauca, P. engelmannii, and their hybrids) and for 281 populations of lodgepole pine (Pinus contorta). Complex multitrait adaptations to different ecological regions such as boreal, montane, coastal, and arid environments accounted for 15 20% of the total variance. This population differentiation could be directly linked to climate variables through multivariate regression tree analysis. Our results suggest that adaptation to climate does not always correspond linearly to temperature gradients. For example, opposite trait values (e.g., early versus late budbreak) may be found in response to apparently similar cold environments (e.g., boreal and montane). Climate change adaptation strategies may therefore not always be possible through a simple shift of seed sources along environmental gradients. For the two species in this study, we identified a relatively small number of uniquely adapted populations (11 for interior spruce and nine for lodgepole pine) that may be used to manage adaptive variation under current and expected future climates. PMID- 26834834 TI - Metagenomic analysis of microbial consortia enriched from compost: new insights into the role of Actinobacteria in lignocellulose decomposition. AB - BACKGROUND: Compost habitats sustain a vast ensemble of microbes specializing in the degradation of lignocellulosic plant materials and are thus important both for their roles in the global carbon cycle and as potential sources of biochemical catalysts for advanced biofuels production. Studies have revealed substantial diversity in compost microbiomes, yet how this diversity relates to functions and even to the genes encoding lignocellulolytic enzymes remains obscure. Here, we used a metagenomic analysis of the rice straw-adapted (RSA) microbial consortia enriched from compost ecosystems to decipher the systematic and functional contexts within such a distinctive microbiome. RESULTS: Analyses of the 16S pyrotag library and 5 Gbp of metagenomic sequence showed that the phylum Actinobacteria was the predominant group among the Bacteria in the RSA consortia, followed by Proteobacteria, Firmicutes, Chloroflexi, and Bacteroidetes. The CAZymes profile revealed that CAZyme genes in the RSA consortia were also widely distributed within these bacterial phyla. Strikingly, about 46.1 % of CAZyme genes were from actinomycetal communities, which harbored a substantially expanded catalog of the cellobiohydrolase, beta-glucosidase, acetyl xylan esterase, arabinofuranosidase, pectin lyase, and ligninase genes. Among these communities, a variety of previously unrecognized species was found, which reveals a greater ecological functional diversity of thermophilic Actinobacteria than previously assumed. CONCLUSION: These data underline the pivotal role of thermophilic Actinobacteria in lignocellulose biodegradation processes in the compost habitat. Besides revealing a new benchmark for microbial enzymatic deconstruction of lignocelluloses, the results suggest that actinomycetes found in compost ecosystems are potential candidates for mining efficient lignocellulosic enzymes in the biofuel industry. PMID- 26834835 TI - Combined laparoscopic pyelolithotomy and endoscopic pyelolithotripsy for staghorn calculi: long-term follow-up results from a case series. AB - PURPOSE: Staghorn renal stones are a challenging field in urology. Due to their high recurrence rates, particularly those associated with an infective process, a complete removal is the ultimate goal in their management. We report our experience with a combined approach of laparoscopic pyelolithotomy and endoscopic pyelolithotripsy, the stone clearance rate, and long-term, follow-up outcomes. METHODS: From June 2012 to October 2014, nine adult patients with large staghorn renal calculi (mean size, 7.2 cm; range, 6.2-9.0 cm) underwent a combined laparoscopic and endoscopic approach. The technique comprised laparoscopic pyelolithotomy and holmium-YAG laser stone fragmentation with the use of a flexible cystoscope introduced through a 12 mm trocar. RESULTS: The average operative time was 140 min (range, 90-190 min). The mean estimated hemoglobin loss was 0.6 mmol/l (range 0.5-0.7 mmol/l). None of the patients required an open surgery conversion. The mean hospital stay was 4 days (range, 2-6 days). A computed tomography urogram control at 6 months of follow up did not show any stone recurrence. CONCLUSIONS: Laparoscopic pyelolithotomy combined with endoscopic pyelolithotripsy could be a therapeutic option in cases where mini invasive procedures, that is, extracorporeal shock wave lithotripsy, ureteroscopic lithotripsy, and percutaneous nephrolithotomy (PCNL) have failed. This technique has a high stone-clearance rate (75-100%) comparable with open surgery and PCNL. However, it could be technically demanding and should be performed by skilled laparoscopy surgeons. PMID- 26834836 TI - Tasquinimod in the treatment of castrate-resistant prostate cancer - current status and future prospects. AB - Treatment options have significantly expanded in recent years for men with metastatic castration-resistant prostate cancer (mCRPC), with the routine use of immunotherapy (sipuleucel-T) and novel hormonal agents such as enzalutamide and abiraterone acetate prior to taxane-based chemotherapy or radium-223 radiotherapy. A number of immune checkpoints limit the immune response of the host to metastatic tumor progression in prostate cancer, one of which is an immunosuppressive and pro-angiogenic cell called the myeloid-derived suppressor cell (MDSC). Tasquinimod is a small molecular oral inhibitor of S100A9, a key cell surface regulator of MDSC function, and has shown anti-angiogenic, antitumor and immune-modulatory properties in preclinical models of prostate cancer and other solid tumors. A large randomized phase II trial of tasquinimod in men with chemotherapy-naive mCRPC demonstrated a significant prolongation in radiographic and symptomatic progression-free survival compared with placebo, which was also associated with improvements in overall survival. Tasquinimod was studied in a global phase III randomized trial in men with bone mCRPC and, while it significantly improved radiographic progression-free survival, this did not result in an overall survival benefit. However, tasquinimod is under evaluation as well as a combination therapy with other systemic agents in prostate cancer and as a single agent in other solid tumors. This review encompasses the preclinical and clinical development of tasquinimod as a therapy for men with prostate cancer. PMID- 26834837 TI - Fixed-dose combination therapy with dutasteride and tamsulosin in the management of benign prostatic hyperplasia. AB - Despite their multifactorial etiology, male lower urinary tract symptoms (LUTS) have been traditionally associated with benign prostatic enlargement (BPE) because of benign prostatic hyperplasia (BPH). Several pharmaceutical therapies have been used to manage LUTS, with alpha1-adrenergic receptor antagonists (alpha1-blockers) and inhibitors of 5alpha-reductase (5alpha-RIs) representing the most commonly prescribed agents currently in use for LUTS treatment. Due to their different modes of action, combined use of alpha1-blockers and 5alpha-RIs has been proven to offer more optimal control of symptoms and better associated quality of life, even though higher rates of adverse events have been shown. Following previous studies on the separate administration of dutasteride and tamsulosin, a fixed-dose combination capsule of tamsulosin 0.4 mg and dutasteride 0.5 mg has been approved and released for clinical use in men with BPH. The present review aims to discuss the rationale behind the combined use of tamsulosin and dutasteride for treating male LUTS, and to present the available data on the role of combination therapy in the management of BPH-related symptoms in terms of efficacy and safety. Special attention is given to the impact of combination treatment on the prevention of clinical progression of BPH. Cost effectiveness of fixed-dose combination and patients' adherence to treatment are also discussed. PMID- 26834838 TI - The role of mycobacterial cell wall nucleic acid complex in the treatment of bacillus Calmette-Guerin failures for non-muscle-invasive bladder cancer. AB - INTRODUCTION: The treatment of high-risk non-muscle-invasive bladder cancer (NMIBC) utilizes transurethral resection followed by adjuvant intravesical immunotherapy or chemotherapy. Intravesical bacillus Calmette-Guerin (BCG) is the mainstay of adjuvant immunotherapy, but there are limited nonsurgical options for patients that fail this treatment. Mycobacterial cell wall nucleic acid complex (MCNA) is an immunotherapeutic agent utilized primarily after failure of intravesical BCG. The purpose of this paper is to provide a comprehensive review of the published literature regarding MCNA. METHODS: A literature review was performed and identified studies indexed in MEDLINE((r)) related to utilization of MCNA for patients with NMIBC. RESULTS: Two trials assessed the efficacy of MCNA in patients with NMIBC, comprising a total of 184 patients. Most patients had carcinoma in situ (CIS) with (26%) or without (52%) concomitant papillary tumors. A minority of patients had only papillary tumors (22%). Most patients (95%) previously received BCG or other intravesical therapy prior to receiving MCNA. In the largest available trial, 25% and 19% of patients had no evidence of residual cancer in 1 and 2 years following initiation of MCNA. A total of 2.3% of patients had adverse events (AEs) leading to delay or discontinuation of therapy and 66% of patients had mild drug-related AEs. CONCLUSION: Based on analysis of available published data, MCNA offers a durable response for a small proportion of patients that have failed prior intravesical therapy. There still exists a large unmet need for nonsurgical treatment options for patients with NMIBC who have failed adjuvant intravesical therapies. PMID- 26834839 TI - The efficacy and tolerability of mirabegron, a beta3 adrenoceptor agonist, in patients with symptoms of overactive bladder. AB - Mirabegron, is the only beta-3 adrenoreceptor (AR) agonist available for the treatment of overactive bladder (OAB). To assess the efficacy and tolerability of this novel drug therapy, two phase II and six phase III Astellas-sponsored trials have been conducted with over 10,500 adults with OAB recruited. Of these, seven were randomized, double blind, 12-week placebo controlled studies and the other was for 12 months and not placebo controlled. The evidence described would suggest that mirabegron is as efficacious as most antimuscarinics, including tolterodine extended release (ER) 4 mg, compared with placebo with regard to objective measures such as reduction in number of voids per 24 hours, mean volume per void, mean number of episodes of general urinary incontinence, urgency urinary incontinence and urgency per 24 hours; and subjective measures such as severity of urgency, patient perception of bladder condition and validated continence quality of life questionnaires. Regarding tolerability, these data would suggest that patients taking mirabegron suffer a similar rate of adverse effects as those taking placebo alone, whereas the rate in those taking antimuscarinics is greater. Thus mirabegron presents a safe and effective alternative treatment to antimuscarinics for patients with OAB symptoms. Patients who may particularly benefit from mirabegron include those who are unsuitable for antimuscarinics or who have previously struggled with antimuscarinic side effects. PMID- 26834841 TI - Pazopanib in the treatment of advanced renal cell carcinoma. AB - Pazopanib is an orally available multitargeted tyrosine kinase inhibitor (a class of targeted therapies) that inhibits tumor angiogenesis and cell proliferation. The safety and efficacy of pazopanib (noninferior to sunitinib for progression free survival) in patients with advanced or metastatic renal cell carcinoma (mRCC) have been demonstrated in several clinical trials. However, in addition to therapeutic efficacy, treatment choices should also take into account health related quality of life (HRQoL) aspects of cancer therapy. Here, we summarize the HRQoL findings related to pazopanib use, based on patient-reported outcome measures; pazopanib has been shown to be superior to sunitinib on several HRQoL domains (including patient preference). A further consideration for treatment choice is how well the findings from clinical trials correlate with evidence from general clinical practice. This review therefore includes descriptions of real world experience of pazopanib use in the treatment of patients with mRCC, following its approval by medical regulatory authorities in a number of countries. Naturalistic observational studies demonstrate that the efficacy of pazopanib in patients with mRCC is consistent with clinical trial findings. Similarly, consistent results were observed for the safety profile of pazopanib between observational studies and clinical trials, with most treatment-associated adverse events being mild to moderate in severity, and manageable. PMID- 26834843 TI - MetFrag relaunched: incorporating strategies beyond in silico fragmentation. AB - BACKGROUND: The in silico fragmenter MetFrag, launched in 2010, was one of the first approaches combining compound database searching and fragmentation prediction for small molecule identification from tandem mass spectrometry data. Since then many new approaches have evolved, as has MetFrag itself. This article details the latest developments to MetFrag and its use in small molecule identification since the original publication. RESULTS: MetFrag has gone through algorithmic and scoring refinements. New features include the retrieval of reference, data source and patent information via ChemSpider and PubChem web services, as well as InChIKey filtering to reduce candidate redundancy due to stereoisomerism. Candidates can be filtered or scored differently based on criteria like occurence of certain elements and/or substructures prior to fragmentation, or presence in so-called "suspect lists". Retention time information can now be calculated either within MetFrag with a sufficient amount of user-provided retention times, or incorporated separately as "user-defined scores" to be included in candidate ranking. The changes to MetFrag were evaluated on the original dataset as well as a dataset of 473 merged high resolution tandem mass spectra (HR-MS/MS) and compared with another open source in silico fragmenter, CFM-ID. Using HR-MS/MS information only, MetFrag2.2 and CFM ID had 30 and 43 Top 1 ranks, respectively, using PubChem as a database. Including reference and retention information in MetFrag2.2 improved this to 420 and 336 Top 1 ranks with ChemSpider and PubChem (89 and 71 %), respectively, and even up to 343 Top 1 ranks (PubChem) when combining with CFM-ID. The optimal parameters and weights were verified using three additional datasets of 824 merged HR-MS/MS spectra in total. Further examples are given to demonstrate flexibility of the enhanced features. CONCLUSIONS: In many cases additional information is available from the experimental context to add to small molecule identification, which is especially useful where the mass spectrum alone is not sufficient for candidate selection from a large number of candidates. The results achieved with MetFrag2.2 clearly show the benefit of considering this additional information. The new functions greatly enhance the chance of identification success and have been incorporated into a command line interface in a flexible way designed to be integrated into high throughput workflows. Feedback on the command line version of MetFrag2.2 available at http://c ruttkies.github.io/MetFrag/ is welcome. PMID- 26834844 TI - Bevacizumab is safe in acute relapses of neuromyelitis optica. AB - OBJECTIVES: Neuromyelitis optica (NMO) is a relapsing autoimmune disease targeting the spinal cord and optic nerve leading to paralysis and blindness. Current treatment for acute NMO attacks is immunosuppression with high-dose corticosteroids and/or plasmapheresis. Preclinical animal studies suggest that bevacizumab might be beneficial in limiting the extent of inflammation during a NMO relapse by reducing the disruption of the blood-brain barrier. METHODS: We carried out an open-label phase 1b safety and proof-of-concept trial in 10 participants with NMO immunoglobulin G seropositive NMO, NMO spectrum disease and those at high risk for developing NMO/NMO spectrum disease who presented with an acute attack of transverse myelitis, optic neuritis or brainstem inflammation. In addition to treating with 1 g of daily intravenous methylprednisolone, we infused 10 mg/kg of bevacizumab intravenously on day 1 of treatment. The primary outcome measure was safety and the secondary outcome measure was efficacy. RESULTS: Of the 10 participants enrolled, five presented with acute transverse myelitis, four with acute optic neuritis and one with a brainstem lesion. Bevacizumab was safe in all 10 participants, with only one serious adverse event within the 90-day follow up that was not attributed to the medication. Three patients recovered to pre-attack neurological function or better, and no patients required escalation to plasmapheresis. CONCLUSIONS: Bevacizumab is a safe add-on therapy to high-dose corticosteroids for NMO/NMO spectrum disease patients presenting with an acute relapse. PMID- 26834845 TI - Osteoporosis therapeutics: recent developments at ASBMR. PMID- 26834840 TI - Testosterone deficiency in the aging male. AB - Treatment for hypogonadism is on the rise, particularly in the aging population. Yet treatment in this population represents a unique challenge to clinicians. The physiology of normal aging is complex and often shares the same, often vague, symptoms of hypogonadism. In older men, a highly prevalent burden of comorbid medical conditions and polypharmacy complicates the differentiation of signs and symptoms of hypogonadism from those of normal aging, yet this differentiation is essential to the diagnosis of hypogonadism. Even in older patients with unequivocally symptomatic hypogonadism, the clinician must navigate the potential benefits and risks of treatment that are not clearly defined in older men. More recently, a greater awareness of the potential risks associated with treatment in older men, particularly in regard to cardiovascular risk and mortality, have been appreciated with recent changes in the US Food and Drug Administration recommendations for use of testosterone in aging men. The aim of this review is to provide a framework for the clinician evaluating testosterone deficiency in older men in order to identify correctly and treat clinically significant hypogonadism in this unique population while minimizing treatment-associated harm. PMID- 26834842 TI - The reproducibility of acquiring three dimensional gait and plantar pressure data using established protocols in participants with and without type 2 diabetes and foot ulcers. AB - BACKGROUND: Several prospective studies have suggested that gait and plantar pressure abnormalities secondary to diabetic peripheral neuropathy contributes to foot ulceration. There are many different methods by which gait and plantar pressures are assessed and currently there is no agreed standardised approach. This study aimed to describe the methods and reproducibility of three-dimensional gait and plantar pressure assessments in a small subset of participants using pre existing protocols. METHODS: Fourteen participants were conveniently sampled prior to a planned longitudinal study; four patients with diabetes and plantar foot ulcers, five patients with diabetes but no foot ulcers and five healthy controls. The repeatability of measuring key biomechanical data was assessed including the identification of 16 key anatomical landmarks, the measurement of seven leg dimensions, the processing of 22 three-dimensional gait parameters and the analysis of four different plantar pressures measures at 20 foot regions. RESULTS: The mean inter-observer differences were within the pre-defined acceptable level (<7 mm) for 100 % (16 of 16) of key anatomical landmarks measured for gait analysis. The intra-observer assessment concordance correlation coefficients were > 0.9 for 100 % (7 of 7) of leg dimensions. The coefficients of variations (CVs) were within the pre-defined acceptable level (<10 %) for 100 % (22 of 22) of gait parameters. The CVs were within the pre-defined acceptable level (<30 %) for 95 % (19 of 20) of the contact area measures, 85 % (17 of 20) of mean plantar pressures, 70 % (14 of 20) of pressure time integrals and 55 % (11 of 20) of maximum sensor plantar pressure measures. CONCLUSION: Overall, the findings of this study suggest that important gait and plantar pressure measurements can be reliably acquired. Nearly all measures contributing to three dimensional gait parameter assessments were within predefined acceptable limits. Most plantar pressure measurements were also within predefined acceptable limits; however, reproducibility was not as good for assessment of the maximum sensor pressure. To our knowledge, this is the first study to investigate the reproducibility of several biomechanical methods in a heterogeneous cohort. PMID- 26834846 TI - Latest therapeutic advances in musculoskeletal disease from the ACR 2015 annual conference. PMID- 26834848 TI - Fibrin glue for olecranon bursitis: a case report. PMID- 26834849 TI - Using law to strengthen health professions: frameworks and practice. AB - The lack of sufficient, high-quality health workers is one of the primary barriers to improving health in sub-saharan africa. An approach to address this challenge is for public health practitioners to increase their cooperation with public health lawyers, regulators and other policymakers in order to develop strengthened health workforce laws, regulations, and policies that are vigorously implemented and enforced. Conceptual frameworks can help clarify the meaning of health system governance and the pathways between law and health. International recommendations for policy interventions governing health workers provide countries with valuable guidance for domestic reforms. Monitoring and evaluation of legal, regulatory, and other policy interventions are required to ascertain their public health impact. At the intersection of law and public health, professionals from both fields can collaborate in concrete ways such as those discussed here to improve laws and policies governing health. PMID- 26834850 TI - Pediatric obesity: Causes, symptoms, prevention and treatment. AB - Pediatric or childhood obesity is the most prevalent nutritional disorder among children and adolescents worldwide. Approximately 43 million individuals are obese, 21-24% children and adolescents are overweight, and 16-18% of individuals have abdominal obesity. The prevalence of obesity is highest among specific ethnic groups. Obesity increases the risk of heart diseases in children and adults. Childhood obesity predisposes the individual to insulin resistance and type 2 diabetes, hypertension, hyperlipidemia, liver and kidney diseases and causes reproductive dysfunction in adults. Obesity in children is a major health concern of the developed world. The National Health and Nutrition Examination Survey has reported that the prevalence of obesity is on the increase in all the pediatric age groups, in males and females, and in various ethnic and racial groups. Factors, such as eating habits, genetics, environment, metabolism, and lifestyle play an important role in the development of obesity. Over 90% of obesity cases are idiopathic and less than 10% are associated with genetic and hormonal causes. Obesity occurs when the body consumes more calories than it burns, through overeating and underexercising. The symptoms of obesity include breathing disorders, sleep apnea, chronic obstructive pulmonary disease, certain types of cancer such as prostate, bowel, breast and uterine, coronary heart disease, diabetes (type 2 in children), depression, liver and gallbladder problems, gastro-esophageal reflux disease, high blood pressure, high cholesterol, stroke, and joint diseases such as osteoarthritis, pain in knees and lower back. Environmental, behavioral such as consumption of convenience foods, genetic, and family factors contribute to pediatric obesity. Obesity can be countered through lower calorie consumption, weight loss and diet programs, as well as increased physical activity. A number of endogenous molecules including leptin, hypothalamic melanocortin 4 receptor, and mitochondrial uncoupling proteins, are known to affect body weight. These molecules serve as potential targets for the pharmacological manipulation of obesity. Sibutramine and orlistat are primariliy used for the treatment of adult obesity, which produces modest weight loss, of 3-8% compared to placebo. For children and obese adolescents, metformin is used in the case of insulin resistance and hyperinsulinemia. Octreotide is used for hypothalamic obesity. Bariatric surgery is performed for the treatment of severe childhood obesity. The causes, symptoms, prevention and treatment of pediatric obesity are described in the present review. PMID- 26834847 TI - Osteoporosis in men: findings from the Osteoporotic Fractures in Men Study (MrOS). AB - The lifespan of men is increasing and this is associated with an increased prevalence of osteoporosis in men. Osteoporosis increases the risk of bone fracture. Fractures are associated with increased disability and mortality, and public health problems. We review here the study of osteoporosis in men as obtained from a longitudinal cohort of community-based older men, the Osteoporotic Fractures in Men Study (MrOS). PMID- 26834852 TI - Fanconi anemia-D1 due to homozygosity for the BRCA2 gene Cypriot founder mutation: A case report. AB - Fanconi anemia (FA) is a rare disorder characterized by multiple congenital malformations, progressive bone marrow failure and susceptibility to malignancies. Biallelic mutations in the breast cancer 2, early onset (BRCA2) gene are responsible for the FA-D1 subgroup, which accounts for ~3% of all the FA cases. Patients with biallelic BRCA2 mutations generally display a more severe phenotype, with earlier onset and increased incidence of leukaemia and other solid tumors, than other patients with FA. In the present report, the first Cypriot patient with FA-D1 is described, which is the fifth case of a homozygote for the same null allele reported thus far, and the third known case of neuroblastoma in association with FA-D1. PMID- 26834851 TI - Molecular biology of gynecological cancer. AB - Cancer is a pathological condition in which the balance between cell growth and death is disordered. Various molecules have been reported to be involved in the oncogenic process of invasion, metastasis and resistance to treatment. An exponential growth in the collection of genomic and proteomic data in the past 20 years has provided major advances in understanding the molecular mechanisms of human cancer, which has been applied to diagnostic and treatment strategies. Targeted therapies have been developed and adopted, particularly for advanced, refractory or recurrent cancers, depending on individual molecular profiles. The aim of the present review is to provide a report of the current literature regarding the molecular biology of gynecological cancers. PMID- 26834854 TI - Association of SIRT1 and HMGA1 expression in non-small cell lung cancer. AB - The roles of Silent mating type information regulation 2 homolog 1 (SIRT1) and High mobility group A1 (HMGA1) in human diseases have been extensively studied separately; however, to the best of our knowledge, the current study is the first to report on their interrelationship in lung cancer. The association of SIRT1 and HMGA1 in non-small cell lung cancer (NSCLC) was investigated by evaluating their expression and prognostic significance in 260 patients with NSCLC using immunohistochemistry. SIRT1 and HMGA1 expression were found to be significantly correlated with each other (P<0.001), and both were significantly associated with clinicopathological parameters, including histological type and degree of differentiation. In squamous cell carcinoma (SCC), SIRT1+ specimens were significantly associated with shorter overall survival (OS) time (P=0.019). However, in patients with adenocarcinoma (AD), no association was identified between SIRT1 and OS. In addition, HMGA1+ specimens were significantly associated with poor differentiation (P=0.028), and were more frequent in SCC than AD (P=0.015). However, HMGA1 was not associated with OS on univariate Cox regression analysis or Kaplan-Meier analysis (both P>0.05). SIRT1/HMGA1 coexpression was significantly associated with male gender (P=0.016), and moderately and poorly differentiated histological grade (P=0.025). The findings indicate that SIRT1 and HMGA1 may have significant effects during tumor progression in NSCLC, particularly in patients with SCC, and are potentially useful as prognostic indicators for patients with NSCLC. PMID- 26834856 TI - Data-adaptive Shrinkage via the Hyperpenalized EM Algorithm. AB - We propose an extension of the expectation-maximization (EM) algorithm, called the hyperpenalized EM (HEM) algorithm, that maximizes a penalized log-likelihood, for which some data are missing or unavailable, using a data-adaptive estimate of the penalty parameter. This is potentially useful in applications for which the analyst is unable or unwilling to choose a single value of a penalty parameter but instead can posit a plausible range of values. The HEM algorithm is conceptually straightforward and also very effective, and we demonstrate its utility in the analysis of a genomic data set. Gene expression measurements and clinical covariates were used to predict survival time. However, many survival times are censored, and some observations only contain expression measurements derived from a different assay, which together constitute a difficult missing data problem. It is desired to shrink the genomic contribution in a data-adaptive way. The HEM algorithm successfully handles both the missing data and shrinkage aspects of the problem. PMID- 26834853 TI - Strategies and developments of immunotherapies in osteosarcoma. AB - Osteosarcoma (OS) is a frequently observed primary malignant tumor. Current therapy for osteosarcoma consists of comprehensive treatment. The long-term survival rate of patients exhibiting nonmetastatic OS varies between 65-70%. However, a number of OS cases have been observed to be resistant to currently used therapies, leading to disease recurrence and lung metastases, which are the primary reasons leading to patient mortality. In the present review, a number of pieces of evidence provide support for the potential uses of immunotherapy, including immunomodulation and vaccine therapy, for the eradication of tumors via upregulation of the immune response. Adoptive T-cell therapy and oncolytic virotherapy have been used to treat OS and resulted in objective responses. Immunologic checkpoint blockade and targeted therapy are also potentially promising therapeutic tools. Immunotherapy demonstrates significant promise with regard to improving the outcomes for patients exhibiting OS. PMID- 26834855 TI - Strain-rate Dependence of Elastic Modulus Reveals Silver Nanoparticle Induced Cytotoxicity. AB - Force-displacement measurements are taken at different rates with an atomic force microscope to assess the correlation between cell health and cell viscoelasticity in THP-1 cells that have been treated with a novel drug carrier. A variable indentation-rate viscoelastic analysis, VIVA, is employed to identify the relaxation time of the cells that are known to exhibit a frequency dependent stiffness. The VIVA agrees with a fluorescent viability assay. This indicates that dextran-lysozyme drug carriers are biocompatible and deliver concentrated toxic material (rhodamine or silver nanoparticles) to the cytoplasm of THP-1 cells. By modelling the frequency dependence of the elastic modulus, the VIVA provides three metrics of cytoplasmic viscoelasticity: a low frequency modulus, a high frequency modulus and viscosity. The signature of cytotoxicity by rhodamine or silver exposure is a frequency independent twofold increase in the elastic modulus and cytoplasmic viscosity, while the cytoskeletal relaxation time remains unchanged. This is consistent with the known toxic mechanism of silver nanoparticles, where metabolic stress causes an increase in the rigidity of the cytoplasm. A variable indentation-rate viscoelastic analysis is presented as a straightforward method to promote the self-consistent comparison between cells. This is paramount to the development of early diagnosis and treatment of disease. PMID- 26834857 TI - Can the activities of the large scale cortical network be expressed by neural energy? A brief review. AB - This paper mainly discusses and summarize that the changes of biological energy in the brain can be expressed by the biophysical energy we constructed. Different from the electrochemical energy, the biophysical energy proposed in the paper not only can be used to simulate the activity of neurons but also be used to simulate the neural activity of large scale cortical networks, so that the scientific nature of the neural energy coding was discussed. PMID- 26834858 TI - On the time course of short-term forgetting: a human experimental model for the sense of balance. AB - The primary aim of this study was to establish whether the decline of the memory of an angular displacement, detected by the semicircular canals, is best characterized by an exponential function or by a power function. In 27 subjects a conflict was created between the semicircular canals and the graviceptive systems. Subjects were seated, facing forwards, in the gondola of a large centrifuge. The centrifuge was accelerated from stationary to 2.5Gz. While the swing out of the gondola (66 degrees ) during acceleration constitutes a frontal plane angular-displacement stimulus to the semicircular canals, the graviceptive systems persistently signal that the subject is upright. During 6 min at 2.5Gz the perceived head and body position was recorded; in darkness the subject repeatedly adjusted the orientation of a luminous line so that it appeared to be horizontal. Acceleration of the centrifuge induced a sensation of tilt which declined with time in a characteristic way. A three-parameter exponential function (Y = Ae(-bt) + C) and a power function (Y = At(-b) + C) were fitted to the data points. The inter-individual variability was considerable. In the vast majority of cases, however, the exponential function provided a better fit (in terms of RMS error) than the power function. The mean exponential function was: y = 27.8e(-0.018t) + 0.5 degrees , where t is time in seconds. Findings are discussed with connection to possible underlying neural mechanisms; in particular, the head-direction system and short-term potentiation and persistent action potential firing in the hippocampus are considered. PMID- 26834859 TI - Exposure to Mozart music reduces cognitive impairment in pilocarpine-induced status epilepticus rats. AB - Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients. PMID- 26834860 TI - Predicting the eye fixation locations in the gray scale images in the visual scenes with different semantic contents. AB - In recent years, there has been considerable interest in visual attention models (saliency map of visual attention). These models can be used to predict eye fixation locations, and thus will have many applications in various fields which leads to obtain better performance in machine vision systems. Most of these models need to be improved because they are based on bottom-up computation that does not consider top-down image semantic contents and often does not match actual eye fixation locations. In this study, we recorded the eye movements (i.e., fixations) of fourteen individuals who viewed images which consist natural (e.g., landscape, animal) and man-made (e.g., building, vehicles) scenes. We extracted the fixation locations of eye movements in two image categories. After extraction of the fixation areas (a patch around each fixation location), characteristics of these areas were evaluated as compared to non-fixation areas. The extracted features in each patch included the orientation and spatial frequency. After feature extraction phase, different statistical classifiers were trained for prediction of eye fixation locations by these features. This study connects eye-tracking results to automatic prediction of saliency regions of the images. The results showed that it is possible to predict the eye fixation locations by using of the image patches around subjects' fixation points. PMID- 26834861 TI - Neural network modelling of the influence of channelopathies on reflex visual attention. AB - This paper introduces a model of Emergent Visual Attention in presence of calcium channelopathy (EVAC). By modelling channelopathy, EVAC constitutes an effort towards identifying the possible causes of autism. The network structure embodies the dual pathways model of cortical processing of visual input, with reflex attention as an emergent property of neural interactions. EVAC extends existing work by introducing attention shift in a larger-scale network and applying a phenomenological model of channelopathy. In presence of a distractor, the channelopathic network's rate of failure to shift attention is lower than the control network's, but overall, the control network exhibits a lower classification error rate. The simulation results also show differences in task relative reaction times between control and channelopathic networks. The attention shift timings inferred from the model are consistent with studies of attention shift in autistic children. PMID- 26834862 TI - A novel algorithm with differential evolution and coral reef optimization for extreme learning machine training. AB - Extreme learning machine (ELM) is a novel and fast learning method to train single layer feed-forward networks. However due to the demand for larger number of hidden neurons, the prediction speed of ELM is not fast enough. An evolutionary based ELM with differential evolution (DE) has been proposed to reduce the prediction time of original ELM. But it may still get stuck at local optima. In this paper, a novel algorithm hybridizing DE and metaheuristic coral reef optimization (CRO), which is called differential evolution coral reef optimization (DECRO), is proposed to balance the explorative power and exploitive power to reach better performance. The thought and the implement of DECRO algorithm are discussed in this article with detail. DE, CRO and DECRO are applied to ELM training respectively. Experimental results show that DECRO-ELM can reduce the prediction time of original ELM, and obtain better performance for training ELM than both DE and CRO. PMID- 26834863 TI - New stability criterion of neural networks with leakage delays and impulses: a piecewise delay method. AB - This paper analyzes the global asymptotic stability of a class of neural networks with time delay in the leakage term and time-varying delays under impulsive perturbations. Here the time-varying delays are assumed to be piecewise. In this method, the interval of the variation is divided into two subintervals by its central point. By developing a new Lyapunov-Krasovskii functional and checking its variation in between the two subintervals, respectively, and then we present some sufficient conditions to guarantee the global asymptotic stability of the equilibrium point for the considered neural network. The proposed results which do not require the boundedness, differentiability and monotonicity of the activation functions, can be easily verified via the linear matrix inequality (LMI) control toolbox in MATLAB. Finally, a numerical example and its simulation are given to show the conditions obtained are new and less conservative than some existing ones in the literature. PMID- 26834864 TI - Imaging Appearances of Paratesticular Fibrous Pseudotumor. AB - BACKGROUND: In this paper the clinical and radiological features of three cases with paratesticular fibrous pseudotumor were presented after a retrospective analysis of medical archives of our hospital. CASE REPORT: Each of the three cases had unilateral, multiple nodular lesions with smooth borders accompanied by a hydrocele. On sonographic examination, the lesions showed echogenicity similar to, or slightly lower than, the testis, and the two large lesions had posterior acoustic shadowing. Color Doppler ultrasound examination of two cases showed intralesional vascularity of mild-to-moderate degree. All lesions appeared hypointense compared to testicular tissue on T1W and T2W magnetic resonance images. Moderate-to-high enhancement was observed in the diffuse pattern after intravenous injection of contrast material. An intraoperative pathological examination was performed and local excision carried out in all three cases. CONCLUSIONS: Fibrous pseudotumor is a rare benign paratesticular lesion, which can be confused with malignant masses. Imaging procedures play an important role in correct diagnosis. Unfamiliarity with imaging findings of paratesticular fibrous pseudotumor may eventuate in an unnecessary orchiectomy. PMID- 26834865 TI - Morphology of Mandibular Incisors: A Study on CBCT. AB - BACKGROUND: The aim of the study was to identify the number of root canals and examine root canal morphology of permanent mandibular incisors in an Indian sub population of Pune, Maharashtra, India using cone-beam computed tomography (CBCT). MATERIAL/METHODS: This study was conducted at Elite CBCT & Dental Diagnostics, Pune. One hundred mandibular incisors were evaluated for the number of root, root canals and root morphology. RESULTS: In the present study, amongst 102 mandibular incisors, all had one root, 36% of them had a second canal, and Vertucci Type I was the most common type. CONCLUSIONS: CBCT imaging is an excellent method for detection of different canal configurations of mandibular incisors. PMID- 26834866 TI - Renal Cell Carcinoma Metastasis to Ipsilateral Parotid and Submandibular Glands: Report of a Case with Sonoelastographic Findings. AB - BACKGROUND: Renal cell carcinoma (RCC) - also known as hypernephroma or grawitz tumor - accounts for 3% of the adulthood malignancies. Approximately 30-40% of the patients have metastasis at the time of the diagnosis and most common sites for metastasis are lung, regional lymph nodes, bone and liver. A total of 8-14% of the patients with RCC has head and neck metastasis. However, metastasis to major salivary glands is rarely seen. In this paper, we aimed to report a RCC case with metastasis to parotid and submandibular glands that has the same sonographic and sonoelastographic findings with the primary tumor. CASE REPORT: 66-year old woman with RCC history was referred to our radiology department for neck ultrasound (US) with painful swelling in the right parotid gland region. A well-defined, 37*21 mm sized hypoechoic heterogeneous solid mass was detected in the superficial-deep lobe of the right parotid gland. The mass was prominently hypervascular in color Doppler ultrasonography scan. Coincidentally, a 13*13 mm hypoechoic lobulated solid mass was detected in the right submandibular gland with similar sonographic findings. Real-time sonoelastography (SEL) was performed to the masses and both of them were blue-green colored that indicates hard tissue. An US and SEL evaluation was also performed to the renal mass (RCC) of the patient. The primary mass was also similar in sonographic and SEL appearance as salivary gland masses. In the patient history, she revealed chemotherapy radiotherapy treatment 1.5 years ago due to inoperable mass in the mid-lower pole of the left kidney diagnosed as clear cell RCC with vascular invasion, liver, lung and brain metastasis. Because of known primary tumor, the masses in the salivary glands were suspected to be metastatic and a tru-cut biopsy was performed. Pathological result was reported as clear cell RCC metastasis. CONCLUSIONS: The etiology of RCC is still unknown and metastatic involvement can be seen at unexpected tissue and organs. Metastatic disease should be considered when a salivary gland mass detected in patients with RCC history. SEL examination would be helpful in differentiation of the origin of the metastatic lesion with known SEL features. PMID- 26834867 TI - Sport and Disabled Individuals - Theory and Practice. PMID- 26834868 TI - Medical Care Before and During the Winter Paralympic Games in Turin 2006, Vancouver 2010 and Sochi 2014. AB - Medical care in disabled sports is crucial both as prophylaxis and as ongoing medical intervention. The aim of this paper was to present changes in the quality of medical care over the consecutive Paralympic Games (PG). The study encompassed 31 paralympians: Turin (11), Vancouver (12), and Sochi (8) competing in cross country skiing, alpine skiing, biathlon and snowboarding. The first, questionnaire-based, part of the study was conducted in Poland before the PG. The athletes assessed the quality of care provided by physicians, physiologists, dieticians, and physiotherapists, as well as their cooperation with the massage therapist and the psychologist. The other part of the study concerned the athletes' health before leaving for the PG, as well as their diseases and injuries during the PG. The quality of medical care was poor before the 2006 PG, but satisfactory before the subsequent PG. Only few athletes made use of psychological support, assessing it as poor before the 2006 PG and satisfactory before the 2010 and 2014 PG. The athletes' health condition was good during all PG. The health status of cross-country skiers was confirmed by a medical fitness certificate before all PG, while that of alpine skiers only before the 2014 PG. There were no serious diseases; training injuries precluded two athletes from participation. The quality of medical care before the PG was poor, however, became satisfactory during the actual PG. The resulting ad hoc pattern deviates from the accepted standards in medical care in disabled sports. PMID- 26834870 TI - Relationships Between Anaerobic Performance, Field Tests and Game Performance of Sitting Volleyball Players. AB - The aim of this study was to evaluate relationships between anaerobic performance, field tests, game performance and anthropometric variables of sitting volleyball players. Twenty elite Polish sitting volleyball players were tested using the 30 s Wingate Anaerobic Test for arm crank ergometer and participated in six physical field tests. Heights in position to block and to spike, as well as arm reach were measured. Players were observed during the game on the court in terms of effectiveness of the serve, block, attack, receive and defense. Pearson analysis and the Spearman's rank correlation coefficient were used. The strongest correlations were found between the chest pass test and mean power and peak power (r=.846; p=.001 and r=.708; p=.0005, respectively), and also between the T-test and peak power (r= -.718; p=.001). Mean power correlated with the 3 m test (r= -.540; p=.014), the 5 m test (r= -.592; p=.006), and the T-test (r= -.582; p=.007). Peak power correlated with the 3 m test (r= -.632; p=.003), the 5 m test (r= -.613; p=.004), speed & agility (r= -.552; p=.012) and speed & endurance (r=-.546; p=.013). Significant correlations were observed between anthropometric parameters and anaerobic performance variables (p<=.001), and also between anthropometric parameters and field tests (p<=.05). Game performance and physical fitness of sitting volleyball players depended on their anthropometric variables: reach of arms, the position to block and to spike. The chest pass test could be used as a non-laboratory field test of anaerobic performance of sitting volleyball players. PMID- 26834869 TI - Atlanto-Axial Instability in People with Down's Syndrome and its Impact on the Ability to Perform Sports Activities - A Review. AB - Atlanto-axial instability (AAI) is a developmental anomaly often occurring in persons with Down's syndrome (DS). According to various reports, AAI affects from 6.8 to 27% of the population with DS. The aim of this review was to illustrate the issue of AAI with regard to the progressively changing state of scientific knowledge. The extended distance between the rear surface of the frontal arcus of the C1 cervical vertebra and the anterior surface of C2 cervical vertebra dens (anterior atlanto-odontoid distance, AAOD) indicates the occurrence of AAI and is detectable through X-ray examination. Hypoplasia of the C2 dens, also detectable through X-ray examination, is another suggested risk factor for AAI. According to current data, the methodology of taking measurements is inconsistent, which leads to errors in interpretation. As research focusing on AAI was progressing, new data emerged from other studies on persons with DS, suggesting that neurological symptoms in persons with DS that indicated the occurrence of spinal cord compression were an important factor in medical imaging detection of AAI. One of the main arguments supporting this thesis is that in isolated cases spinal cord (SC) damage was noted during screening examinations conducted on a large population of subjects. Moreover, cases in which the neurological symptoms indicate spinal cord compression existed long before the occurrence of the actual damage also remain of significant importance. Therefore, it is necessary to promote neurological studies on persons with DS to enable early diagnosis of spinal cord compression and, at the same time, reduce the use of medical imaging in cases of neurological symptoms. PMID- 26834871 TI - Kinetic and Kinematic Differences in a Golf Swing in One and Both Lower Limb Amputees. AB - Amputee golfers need to cope with the absence of sole proprioception, a decreased range of swing motion and other factors which should be recognized for training purposes. The aim of this study was to determine the kinetic and kinematic differences in the golf swing in one leg and two legs amputees. The participants consisted of two males and one female at a professional or amateur level with a different degree of disability. Each participant was taped by 3D markers and performed five golf swings with the iron 6. The intraclass correlation coefficient (ICC) did not vary between individuals in kinematics, however, it was low in kinetic variables of two leg amputees. The Kendal rank correlation showed a significant relationship between the level of amputation and a large number of kinetic and kinematic variables such as X factor, O factor, S factor and individual body angles. The fluency and similarity of the golf swing did not depend on the level of amputation. One lower limb amputation did not seem to increase movement variability contrary to two lower limb amputation. The most variable parameter was a weight-shift in all golfers. The takeaway and horizontal force angle depended on the level of amputation rather than individual technique, thus, their modification by training may be difficult. Estimation of golf swing "mistakes" in amputees in respect to the leading arm in an early follow or late follow position appeared to be useless. PMID- 26834872 TI - Game Performance Evaluation in Male Goalball Players. AB - Goalball is a Paralympic sport exclusively for athletes who are visually impaired and blind. The aims of this study were twofold: to describe game performance of elite male goalball players based upon the degree of visual impairment, and to determine if game performance was related to anthropometric characteristics of elite male goalball players. The study sample consisted of 44 male goalball athletes. A total of 38 games were recorded during the Summer Paralympic Games in London 2012. Observations were reported using the Game Efficiency Sheet for Goalball. Additional anthropometric measurements included body mass (kg), body height (cm), the arm span (cm) and length of the body in the defensive position (cm). The results differentiating both groups showed that the players with total blindness obtained higher means than the players with visual impairment for game indicators such as the sum of defense (p = 0.03) and the sum of good defense (p = 0.04). The players with visual impairment obtained higher results than those with total blindness for attack efficiency (p = 0.04), the sum of penalty defenses (p = 0.01), and fouls (p = 0.01). The study showed that athletes with blindness demonstrated higher game performance in defence. However, athletes with visual impairment presented higher efficiency in offensive actions. The analyses confirmed that body mass, body height, the arm span and length of the body in the defensive position did not differentiate players' performance at the elite level. PMID- 26834873 TI - Electromyographic Analysis of the Hip Extension Pattern in Visually Impaired Athletes. AB - The objective of the study was to determine the order of muscle recruitment during the active hip joint extension in particular positions in young visually impaired athletes. The average recruitment time (ART) of the gluteus maximus (GM) and the hamstring muscle group (HMG) was assessed by the means of surface electromyography (sEMG). The sequence of muscle recruitment in the female and male group was also taken into consideration. This study followed a prospective, cross - sectional, randomised design, where 76 visually impaired athletes between the age of 18-25 years were enrolled into the research and selected on chosen inclusion and exclusion criteria. Finally, 64 young subjects (32 men and 32 women) were included in the study (age: 21.1 +/- 1.05 years; body mass: 68.4 +/- 12.4 kg; body height: 1.74 +/- 0.09 m; BMI: 22.20 +/- 2.25 kg/m2). All subjects were analysed for the ART of the GM and HMG during the active hip extension performed in two different positions, as well as resting and functional sEMG activity of each muscle. Between gender differences were comprised and the correlations between the ART of the GM and HMG with their functional sEMG activity during hip extension in both positions were shown. No significant differences between the ART of the GM and HMG were found (p>0.05). Furthermore, there was no significant difference of ART among both tested positions, as well in male as female subjects (p>0.05). PMID- 26834874 TI - Laboratory and Field-Based Evaluation of Short-Term Effort with Maximal Intensity in Individuals with Intellectual Disabilities. AB - Results of previous studies have not indicated clearly which tests should be used to assess short-term efforts of people with intellectual disabilities. Thus, the aim of the present study was to evaluate laboratory and field-based tests of short-term effort with maximal intensity of subjects with intellectual disabilities. Twenty four people with intellectual disability, who trained soccer, participated in this study. The 30 s Wingate test and additionally an 8 s test with maximum intensity were performed on a bicycle ergometer. The fatigue index, maximal and mean power, relative maximal and relative mean power were measured. Overall, nine field-based tests were conducted: 5, 10 and 20 m sprints, a 20 m shuttle run, a seated medicine ball throw, a bent arm hang test, a standing broad jump, sit-ups and a hand grip test. The reliability of the 30 s and 8 s Wingate tests for subjects with intellectual disability was confirmed. Significant correlation was observed for mean power between the 30 s and 8 s tests on the bicycle ergometer at a moderate level (r >0.4). Moreover, significant correlations were indicated between the results of laboratory tests and field tests, such as the 20 m sprint, the 20 m shuttle run, the standing long jump and the medicine ball throw. The strongest correlation was in the medicine ball throw. The 30 s Wingate test is a reliable test assessing maximal effort in subjects with intellectual disability. The results of this research confirmed that the 8 s test on a bicycle ergometer had a moderate correlation with the 30 s Wingate test in this population, thus, this comparison needs further investigation to examine alternativeness of the 8 s to 30 s Wingate tests. The non-laboratory tests could be used to indirectly assess performance in short-term efforts with maximal intensity. PMID- 26834875 TI - Effects of Krankcycle Training on Performance and Body Composition in Wheelchair Users. AB - Innovation in training equipment is important for increasing training effectiveness, performance and changes in body composition, especially in wheelchair users with paraplegia. The main objective of a workout session is to induce an adaptation stimulus, which requires overload of involved muscles by voluntary effort, yet this overload may be highly influenced by the size of the spinal cord lesion. Krancykl construction is designed to allow exercise on any wheelchair and with adjustable height or width of crank handles, where even the grip handle may be altered. The aim of this study was to determine the differences in body composition, performance and the rate of perceived exertion (RPE) in paraplegics with a different level of paralyses after a 12 week training programme of a unilateral regime on Krankcycle equipment (a crank machine). The study sample included four men and one women at a different spine lesion level. The 12 weeks programme was successfully completed by four participants, while one subject got injured during the intervention process. Three participants were paraplegics and one was quadriplegic with innervation of the biceps humeri, triceps humeri and deltoideus. The Krankcycle 30 min programme was followed by four other exercises, which were performed after themselves rather than in a circuit training manner as the latter would result in much longer rest periods between exercises, because paraplegics have to be fixed by straps during exercise on hydraulic machines. The RPE after the workout decreased following the twelve week adaptation period. PMID- 26834876 TI - Sexuality of Disabled Athletes Depending on the Form of Locomotion. AB - The main purpose of this study was to determine sexuality of disabled athletes depending on the form of locomotion. The study included 170 disabled athletes, aged between 18 and 45. The entire population was divided into 3 research groups depending on the form of locomotion: moving on wheelchairs (n=52), on crutches (n=29) and unaided (n=89). The research tool was a questionnaire voluntarily and anonymously completed by the respondents of the research groups. The questionnaire was composed of a general part concerning the socio-demographic conditions, medical history, health problems, a part dedicated to physical disability as well as the Polish version of the International Index of Erectile Function (IIEF) and the Female Sexual Function Index (FSFI) evaluating sexual life. STATISTICA 10.0 for Windows was used in the statistical analysis. Subjects moving on crutches were significantly older than ones moving on wheelchairs and unaided (34.41 +/-11.00 vs. 30.49 +/-10.44 and 27.99 +/-10.51 years, respectively) (p=0.018). Clinically significant erectile dysfunctions were most often diagnosed in athletes moving on wheelchairs (70.27%), followed by athletes moving on crutches and moving unaided (60% and 35.42%, respectively; p=0.048). Clinical sexual dysfunctions were diagnosed on a similar level among all female athletes. It was concluded that the form of locomotion may determine sexuality of disabled men. Males on wheelchair revealed the worst sexual functioning. Female athletes moving on wheelchairs, on crutches and moving unaided were comparable in the aspect of their sexual life. PMID- 26834877 TI - Visual Impairment does not Limit Training Effects in Development of Aerobic and Anaerobic Capacity in Tandem Cyclists. AB - The study aimed to investigate the differences in the effects of 7-month training on aerobic and anaerobic capacity in tandem cycling athletes with and without visual impairment. In this study, Polish elite (n=13) and sub-elite (n=13) visually impaired (VI) (n=13; 40.8 +/-12.8 years) and properly sighted (PS) (n=13; 36.7 +/-12.2 years) tandem-cycling athletes participated voluntarily in 7 month routine training. The following pre-/post-training measurements were conducted on separate days: maximal oxygen uptake (VO2max) was estimated with age correction using the Physical Working Capacity test on a bicycle ergometer according to the Astrand-Ryhming method. Maximal power output (Pmax) was evaluated using the Quebec test on a bicycle ergometer. At baseline, VO2max (47.8 +/-14.1 vs 42.0 +/-8.3 ml/kg/min, respectively) and Pmax (11.5 +/-1.5 vs 11.5 +/ 1.0 W/kg) did not differ significantly between PS and VI cyclists. However, differences in aerobic capacity were considered as clinically significant. Two way ANOVA revealed that after 7 month training, there were statistically significant increases in VO2max (p=0.003) and Pmax (p=0.009) among VI (VO2max, +9.1%; Pmax, +6.3%) and PS (VO2max, +9.1%; Pmax, +11.7%) cyclists, however, no time * visual impairment interaction effect was found (VO2max, p=0.467; Pmax, p=0.364). After training, VO2max (p=0.03), but not Pmax (p=0.13), was significantly greater in elite compared to sub-elite tandem cyclists. VI and PS tandem cyclists showed similar rates of improvement in VO2max and Pmax after 7 month training. VO2max was a significant determinant of success in tandem cycling. This is one of the first studies providing reference values for aerobic and anaerobic capacity in visually impaired cyclists. PMID- 26834878 TI - Balance Functional Assessment in People with Visual Impairment. AB - The aims of this study were twofold: to assess the level of balance of people with visual impairment against the BOT-2 standard scores for the able-bodied, and to identify in which trials subjects had the greatest difficulties in maintaining balance with respect to the degree of vision loss and age categories. One hundred twenty-seven subjects with visual impairment aged 6-16 years, participated in the study (68 girls and 59 boys). The division for partially sighted people (61) and the blind (66) was made according to the WHO classification. Functional balance assessment was made using a balance subtest from the Bruininks-Oseretsky test. Significant relationships were noticed between age and the level of balance (chi2 = 8.35 p <0,05), as well as between the degree of vision loss and the level of balance (chi2 = 24.53 p <0,001). The level of balance of almost all blind subjects was below (20%) or well-below (60%) the average for the able-bodied. The subjects' ability to maintain balance was not dependent on gender and was associated primarily with the degree of visual impairment and age. Partially sighted people had better balance than the blind and the decrease in visual acuity resulted in reduction of balance skills. The lowest level of balance was observed in blind students aged 7-11 years. Elaborating physical fitness improvement programs for children and adolescents with visual impairment, diversity of age, the degree of vision loss and limitations of ablility to maintain balance should be taken into account. PMID- 26834879 TI - Standards of Conditions During Preparations for the Summer Paralympic Games Between 2004 and 2012 Assessed by Polish Athletes. AB - The quality of training conditions affects sporting success, injuries and health. The aim of the work was to present the conditions during the preparations of Polish athletes for the Summer Paralympic Games 2004-2012. The study encompassed 271 paralympians: Athens (91), Beijing (89) and London (91), competing in 13 disciplines. The research was based on a two-part questionnaire by Klodecka Rozalska adjusted for disabled sports, and was conducted one month before each PG. Part 1 contained 20 closed-ended questions regarding conditions during preparations, while Part 2 concerned socio-demographic and sports-related data. Three levels of conditions: good, satisfactory and poor, were identified. The analysis showed that while the relationships between the athletes were good in all the preparatory periods, the co-operation with the paralympic coaches worsened. The standards of accommodation, food and sports facilities lowered. Personal orthopaedic supply was satisfactory in London; personal sporting equipment was good at all PG. The quality of medical care was the highest in London. The co-operation with physicians, physiotherapists and massage therapists was satisfactory. Consultations with the dietician were sporadic and assessed as poor. Psychological consultations were rare but satisfactory in Beijing and London. Contacts with the mass media were poor at all PG. Although combining private life, work, and education with sport was satisfactory, it was increasingly difficult to manage, particularly before London. The conditions during preparations for the PG 2004-2012 varied. Improvement was noticed only in the quality of medical care and personal orthopaedic supply. PMID- 26834880 TI - Sports Injuries in Wheelchair Rugby - A Pilot Study. AB - The aim of the study was to analyze etiology and the incidence of sports injuries among wheelchair rugby players. Moreover, we verified if the levels of aggressiveness and anger presented by the athletes and their roles in the team influenced the incidence and severity of the injuries. The study involved 14 male players, members of the Polish National Wheelchair Rugby Team. During a 9-month period, the athletes participated in up to 9 training camps and 4 Wheelchair Rugby tournaments. The study was based on the Competitive Aggressiveness and Anger Scale, registry of sports injuries consulted and non-consulted with a physician and a demographic questionnaire. The following observations were made during the 9-month period corresponding to a mean of 25 training and tournament days: 1) wheelchair rugby players experienced primarily minor injuries (n=102) that did not require a medical intervention, 2) only four injuries needed to be consulted by a physician, 3) sports injuries occurred more frequently among offensive players than in defensive players, 4) offensive players showed a tendency to higher levels of anger and aggressiveness than defensive players. It can be concluded that wheelchair rugby is a discipline associated with a high incidence of minor injuries that do not require a medical intervention. The incidence rate of injuries during the analyzed period was 0.3 per athlete per training day. PMID- 26834881 TI - Hand Grip Strength Vs. Sprint Effectiveness in Amputee Soccer Players. AB - Amputee soccer is one of the types of soccer designed for the disabled, especially those who have undergone amputations, as well as those with extremity dysfunction. The objective of the study was to find the relationship between hand grip strength and sprint time in amputee soccer players. Thirteen field amputee soccer players participated in the study. A SAEHAN hydraulic hand dynamometer manufactured by Jamar was used for hand grip strength measurements. The sprint running test was conducted over a distance of 30 m. The Fusion Smart Speed System was employed for running time measurements. No statistically significant relationships were found between hand grip strength of the left or right hand, and sprint times over 1, 5, 10, 15, 20, 25 and 30 m. Analysis of the running velocity curve of the subjects showed an interesting profile characterized by a 15 meter-long acceleration phase and a significant velocity increase over a distance of 20 - 25 m. The study suggests that there is no relationship between hand grip strength and sprint effectiveness in amputee soccer players. The specificity of locomotion with the use of elbow crutches among elite Polish amputee soccer players probably accounts for the profile of the sprint velocity curve. Extension of the acceleration phase in the sprint run and a velocity increase in the subsequent part of the run were observed. PMID- 26834882 TI - Evaluation of Lipid Metabolism and Nutritional Status in Male Goalball Players. AB - Lipid disorders, obesity and overweight are considered one of the most important modifiable cardiovascular risk factors. Population surveys carried out in Poland have demonstrated a tendency for lipid disorders to occur in 70% and overweight and obesity in more than half of Poles. No such studies have been conducted in groups of people with vision impairment so far. Yet, regular involvement of visually impaired people in sports is likely to reduce cardiovascular risk. Therefore, the authors attempted to evaluate the lipid profile and nutritional status of male goalball players. Thirty two blind or visually impaired male goalball players aged 20 to 45 years participated in the study during which somatic variables (BH, BM, WC, VFR, BMI) and the lipid profile (TC, LDL, HDL, TG) were evaluated. Overweight was found in 40.6% of athletes, with obesity being at the level of 9.3%. A high correlation was found between visceral fat and the BMI (r=0.7; p<0.001), as well as between visceral fat and WC (r=0.8; p<0.001). Abnormal total cholesterol levels were recorded for LDL (22% of study participants), HDL (17%) and triglycerides (13%). Lower levels of individual components of lipid profiles (and higher levels for HDL) were found in athletes with a normal BMI. A correlation was found between the BMI and TG (r=0.4, p<0.01), WC and TG (r=0.4, p<0.01), VFR and LDL ( r=0.4, p<0.05) and TG (r=0.5, p<0.001). The percentage of overweight and obese subjects with vision impairment was lower compared to the general population of men in Poland, with a more beneficial lipid profile. Regular physical activity of the study participants is likely to have a positive effect on their health. PMID- 26834883 TI - Comparison of Designated Coefficients and their Predictors in Functional Evaluation of Wheelchair Rugby Athletes. AB - The objectives of the present study were twofold: to determine differences between groups by means of chosen coefficients and to create significant predictors using regression models for athletes in wheelchair rugby who had the same spinal cord injury (tetraplegia) and were classified as low point and high point players. The study sample consisted of 24 subjects, who had sustained cervical spinal cord injury (CSCI). They were divided into low point (n=15) and high point (n=9) groups according to the IWRF Classification System. A one-way ANOVA revealed statistically significant differences in the following coefficients differentiating the groups: AC (eta2=0.778), LC (eta2=0.687), IC (eta2=0.565), SC (eta2=0.580). The Tukey's HSD post-hoc test indicated statistically significant higher values of coefficients in the HP compared to the LP group: AC=0.958 (p=0.022), LC=0.989 (p=0.031), IC=0.971 (p=0.044), SC=0.938 (p=0.039). In the HP group, the most significant predictor was the sum of visceral and trunk fat which was negatively correlated with the SC (what constituted a positive adaptive change in response to training). With regard to the LP group, body height and circumference of the chest appeared to be most significant predictors and were positively correlated with the SC. In the LP group no predictor with respect to the SC was significantly correlated to sports training. Therefore, the functional classification system confirmed lower status of the LP players. The results of the present study indicate that both metabolic and somatic profiles which highly determine potential of wheelchair rugby athletes are significantly different in LP and HP players, what confirms the reliability of the functional classification system. PMID- 26834884 TI - Changes in Body Composition and Physical Performance in Wheelchair Basketball Players During a Competitive Season. AB - The present study analyzed the changes in body composition and physical performance in wheelchair basketball (WB) players during one competitive season. Players from a WB team competing in the first division of the Spanish League (n = 8, age: 26.5 +/- 2.9 years, body mass: 79.8 +/- 12.6 kg, sitting height: 91.4 +/- 4.4 cm) participated in this research. The upper limbs showed a decrease in subcutaneous adipose tissue and there was an improvement in physical abilities such as sprinting with the ball (5 and 20 m), handgrip and aerobic capacity. However, the changes in physical fitness concerning sprinting without the ball and agility tests were low. It would be interesting to study the effects of implementing specific programs to improve physical performance in WB and to establish more test sessions to monitor the effects of the programs followed. PMID- 26834885 TI - A rewarding journey. PMID- 26834886 TI - Urology trainees: Our future. PMID- 26834887 TI - CPD for community urologists. PMID- 26834888 TI - Severe emphysematous cystitis: Images in urology. PMID- 26834889 TI - Picking your prostates. PMID- 26834891 TI - Ultrasound: A poor diagnostic test for cryptorchidism. PMID- 26834890 TI - Is orchiectomy always necessary in retroperitoneal extragonadal germ cell tumours? PMID- 26834892 TI - Tailor-made medical education. PMID- 26834893 TI - The importance of increasing urology exposure among undergraduates: A U.K. Perspective. PMID- 26834894 TI - Increasing urology exposure among undergraduates: A U.K. Perspective Authors' response. PMID- 26834896 TI - [Not Available]. PMID- 26834895 TI - [Not Available]. PMID- 26834897 TI - A novel approach to the repair of urethrocutaneous fistulae arising after abdominoperineal anorectal resection. AB - This case report describes a novel approach to the repair of perineal urethrocutaneous fistulae (UCF) after abdominoperineal resection (APR). A 62-year old patient developed a UCF after an APR for rectal cancer complicated by perineal abscess formation. The patient presented with continuous urinary drainage from the fistula that persisted despite a number of conservative and surgical measures. The patient underwent successful repair of the urethrocutaneous fistula in prone position-an approach that has not previously been described in the literature. Repair was performed by the multi-disciplinary team of a reconstructive urologist, colorectal surgeon, and plastic surgeon. Post operative retrograde urethrogram demonstrated the absence of a persistent fistula tract and the patient has been continent for 18 months. The prone approach for UCF repair allows for excellent access to the fistula tract for posterior urethroplasty in a patient that has had prior APR. PMID- 26834898 TI - Simultaneous percutaneous nephrolithotomy and early endoscopic ureteric realignment for iatrogenic ureteropelvic junction avulsion during ureteroscopy. AB - We present a case report of successful management of ureteropelvice junction avulsion during ureteroscopy successfully managed with simultaneous percutaneous nephrolithotomy and early endoscopic ureteral realignment. PMID- 26834899 TI - A single-centre experience with tumour tract seeding associated with needle manipulation of renal cell carcinomas. AB - With the rise in detection of incidental renal masses on imaging, there has been a commensurate rise in the use of percutaneous biopsies for evaluation of these tumours. Tumour tract seeding had previously been one of the most feared complications of percutaneous biopsy of renal cell carcinoma (RCC). Recently, less emphasis has been placed on this complication, with the assertion that it has only been reported eight times in literature, and thus must be exceedingly rare. However, we report two cases of tumour tract seeding associated with percutaneous biopsy and treatment of RCC over a short time period at a single institution. This report challenges the current extremely low estimates of the frequency of this complication and calls for a more realistic assessment. PMID- 26834900 TI - Large retroperitoneal hemangioma encompassing the renal vein. AB - Retroperitoneal hemangioma (RH) is a rare and benign vascular malformation. RH may be detected incidentally or present with symptoms due to local invasion of adjacent structures. Management options include surgical resection, as well as serial observation with routine imaging. We describe a retroperitoneal hemangioma encompassing the renal vein that was discovered during diagnosis of acute appendicitis, and characterize diagnostic magnetic resonance imaging (MRI) findings seen with this condition. PMID- 26834901 TI - Bleeding due to ectopic varices in a urinary diversion: A multidisciplinary diagnostic and therapeutic challenge. AB - The ectopic varices in patients with portal hypertension are those that occur at any level of the gastrointestinal (GI) tract, regardless of the varices that occur at the esophageal level. These ectopic varices account for 2-5% of the causes of GI bleeding varices. The risk of bleeding is quadrupled compared to the esophagogastric area, with a mortality of up to 40%. The transjugular intrahepatic portosystemic shunt, should be considered in cases secondary to recurrent bleeding varices. We present a case report of an urological emergency of bleeding in a urinary diversion secondary to ectopic varices successfully treated through the placement of transjugular intrahepatic portosystemic shunt. The condition described here is rare, but important, as it can be a life threatening complication of portal hypertension. This kind of complication should be known by urologic surgeons managing patients with urinary diversions. PMID- 26834902 TI - Urethral injury in laparoscopic-assisted abdominoperineal resection. AB - We present a 71-year-old man who underwent laparoscopic-assisted abdominoperineal resection for recurrence of rectal cancer, which was complicated by a urethral injury. Traumatic urinary catheter insertion was ruled out as an alternative etiology. This case highlights the importance of recognizing urethral injury as a possible complication of laparoscopic-assisted abdominoperineal resection surgery. PMID- 26834903 TI - Muscle invasive bladder cancer culminating with leptomeningeal carcinomatosis. AB - This case reports highlights a rare metastatic manifestation of transitional cell carcinoma of the bladder. The onset of symptoms associated with meningeal irritation should be investigated. However, there is little consensus in the treatment of leptomeningeal carcinomatosis and it should be considered a poor prognostic sign with symptomatic management. PMID- 26834904 TI - Acquired hemophilia A: A rare cause of gross hematuria. AB - Acquired hemophilia A is a rare condition caused by spontaneous development of factor VIII inhibitor. This condition most commonly presents with multiple hemorrhagic symptoms and isolated hematuria is exceedingly rare. Early diagnosis is important, as this condition carries a high mortality rate (13-22%). We present a case of an 82-year-old man with isolated hematuria caused by a factor VIII inhibitor who was successfully treated with recombinant activated factor VII concentrate, as well as prednisone and cyclophosphamide. PMID- 26834905 TI - Multiple secondary malignancies following radiation therapy for testicular cancer. AB - Testicular germ cell tumours (TGCT) are a rare malignancy that affect primarily young men. We present an interesting case of non-seminoma testicular cancer treated with external beam radiation therapy (RT), which subsequently resulted in two separate secondary malignancies decades after initial treatment. PMID- 26834906 TI - Malakoplakia of the prostate masquerading as locally advanced prostate cancer on mpMRI. AB - A 66-year-old man was referred for urological evaluation for an abnormal digital rectal exam (cT2a, subtle nodule at left base, 121 cc prostate) and an elevated prostate specific antigen (PSA) of 8.0 ng/ml. Subsequent 12-core transrectal ultrasound (TRUS)-guided biopsy revealed Gleason 3+4 adenocarcinoma in seven of 12 cores, including all six cores on the right side and one core at the left apex. No extraprostatic extension was identified. Post-biopsy, the patient developed urinary retention requiring a catheter, as well as an Escherichia coli (E. coli) urinary tract infection (UTI) requiring hospitalization and intravenous antibiotics. PMID- 26834907 TI - Incidentally diagnosed post-cesarean vesicouterine fistula (Youssef's syndrome). AB - Vesicouterine fistula (VUF) is a very rare occurrence and is estimated to occur in only 1-4% of all genitourinary fistulas; 90% of cases are Youssef syndrome, which is accompanied by amenorrhea and cyclic hematuria (menouria). In this article, a renal transplant donor who was incidentally diagnosed with Youssef syndrome 20 years after a second cesarean delivery. PMID- 26834908 TI - SEMIPARAMETRIC TIME TO EVENT MODELS IN THE PRESENCE OF ERROR-PRONE, SELF-REPORTED OUTCOMES-WITH APPLICATION TO THE WOMEN'S HEALTH INITIATIVE. AB - The onset of several silent, chronic diseases such as diabetes can be detected only through diagnostic tests. Due to cost considerations, self-reported outcomes are routinely collected in lieu of expensive diagnostic tests in large-scale prospective investigations such as the Women's Health Initiative. However, self reported outcomes are subject to imperfect sensitivity and specificity. Using a semiparametric likelihood-based approach, we present time to event models to estimate the association of one or more covariates with a error-prone, self reported outcome. We present simulation studies to assess the effect of error in self-reported outcomes with regard to bias in the estimation of the regression parameter of interest. We apply the proposed methods to prospective data from 152,830 women enrolled in the Women's Health Initiative to evaluate the effect of statin use with the risk of incident diabetes mellitus among postmenopausal women. The current analysis is based on follow-up through 2010, with a median duration of follow-up of 12.1 years. The methods proposed in this paper are readily implemented using our freely available R software package icensmis, which is available at the Comprehensive R Archive Network (CRAN) website. PMID- 26834909 TI - [Suspected pulmonary opacity in a patient with systemic sclerosis]. PMID- 26834910 TI - Analysis of licensed South African diagnostic imaging equipment. AB - INTRODUCTION OBJECTIVE: To conduct an analysis of all registered South Africa (SA) diagnostic radiology equipment, assess the number of equipment units per capita by imaging modality, and compare SA figures with published international data, in preparation for the introduction of national health insurance (NHI) in SA. METHODS: The SA Radiation Control Board's database of registered diagnostic radiology equipment was analysed by modality, province and healthcare sector. Access to services was reflected as number of units/million population, and compared with published international data. RESULTS: General X-ray units are the most equitably distributed and accessible resource (34.8/million). For fluoroscopy (6.6/million), mammography (4.96/million), computed tomography (5.0/million) and magnetic resonance imaging (2.9/million), there are at least 10 fold discrepancies between the least and best resourced provinces. Although SA's overall imaging capacity is well above that of other countries in sub-Saharan Africa, it is lower than that of all Organisation for Economic Co-operation and Development (OECD). While SA's radiological resources most closely approximate those of the United Kingdom, they are substantially lower than the UK. CONCLUSION: SA access to radiological services is lower than that of any OECD country. For the NHI to achieve equitable access to diagnostic imaging for all citizens, SA will need a more homogeneous distribution of specialised radiological resources and customized imaging guidelines. PMID- 26834911 TI - [A rare and fulminant form of gastritis: emphysematous gastritis]. PMID- 26834912 TI - [Chronic noncommunicable diseases in Senegalese soldiers: cross-sectional study in 2013]. PMID- 26834913 TI - Rubella outbreak investigation, Gokwe North District, Midlands province, Zimbabwe, 2014 - a case control study. AB - INTRODUCTION: Rubella is a contagious disease, caused by rubella virus and transmitted via the respiratory route. Rubella in pregnancy may cause Congenital Rubella Syndrome (CRS), characterized by multiple defects to the brain, heart, eyes and ears. Gokwe North experienced an increase in rubella cases from 6 cases (24 June 2014) to 374 cases (12 August 2014). The study was conducted to determine risk factors associated with contracting rubella. METHODS: A 1:1 unmatched case control study was conducted. A case was a child <15 years, resided in Gokwe North, with maculopapular rash and tested positive for rubella specific IgM or was linked epidemiologically to a laboratory confirmed case. Blood was collected for laboratory diagnosis. An interviewer administered questionnaire was used. Epi InfoTM was used to analyze data. RESULTS: Eighty eight cases and 88 controls were recruited, median age for cases was 7 years (Q1 = 4, Q3 = 8) and 6 years (Q1 = 3, Q3 = 9) for controls. Independent risk factors for contracting rubella were; classmate contact (AOR 9.44; (95% CI 4.29-20.77)) and having >3 children in a household (AOR 2.59; 95%CI (1.23-5.42)). Only 10.2% and 6.8% of the caregivers' cases and controls respectively, knew rubella is spread through contact with an infected person (p = 0.57). Majority of caregivers (97.8%) reported to the health facility within two days of onset of rash. CONCLUSION: Outbreak was driven by contact at school and was spread into the community through school children. Screening and isolation of the sick controlled the outbreak. Routine rubella vaccination could be considered to prevent similar outbreaks. PMID- 26834914 TI - [Diagnostic approach of macular degeneration with "spectral-domain" OCT: clinical case]. PMID- 26834915 TI - [Aspects of Pap smears among women living with HIV followed in Thies / Senegal and association with the degree of immunosuppression]. PMID- 26834916 TI - Intracranial epidural hematoma in a newborn with DIC secondary to congenital rubella. PMID- 26834917 TI - Videocapsule retention: role of surgical treatment (a case report). AB - Video capsule endoscopy (VCE) is a safe innovative tool for investigating obscure gastrointestinal diseases. The capsule is usually excreted with faeces within 24 48 h. Retention of capsule rarely occurs, and it usually depends on the indication of VCE. Retention may long remain asymptomatic or manifest as subocclusif syndrome. Acute complications of retention are very rare but can be life-threatening illness. Surgical approach is considered effective to retrieve the retained capsule, treat the pathology responsible and prevent acute complications. We report the case of a 30 years old patient, followed for Crohn's disease. She received during the assessment reviewed by VCE that has been held for three months. The retention caused subocclusif symptoms of which had needed surgically procedure. Treatment consisted of remove the VCE and repair of stenosis of small bowel by stricturoplasty. PMID- 26834918 TI - [Spontaneous rupture of hepatocellular carcinoma: an emergency diagnosis to know about]. PMID- 26834919 TI - [Study of strabismus in children 0-15 years followed in Lubumbashi, Democratic Republic of Congo: Analysis of epidemiological and clinical aspects]. PMID- 26834920 TI - [Endoscopic treatment of biliary complications of hepatic hydatid disease]. PMID- 26834921 TI - Client perception of service quality at the outpatient clinics of a General hospital in Lagos, Nigeria. AB - INTRODUCTION: Service quality assessments have assumed increasing importance in the last two decades. They are useful in identifying gaps in services been provided with the ultimate aim of guaranteeing quality assurance. The objective of this study was to assess the client perception of service quality at the outpatient clinics of Randle General hospital, Lagos. METHODS: A descriptive cross sectional study was conducted from March to May 2013. A multistage sampling technique was used to select respondents and data was collected with the aid of modified SERVQUAL questionnaires. The data was analysed with aid of EPI-INFO 2002 and statistical significance was set at a P value 0.05 for statistical significance. RESULTS: Total of 400 respondents were interviewed. The mean age was 40 years with a standard deviation of 15.2 yrs. The highest mean score of 4.35 out of a possible maximum of 5 was recorded in assurance domain while the lowest mean score of 4.00 was recorded in the responsiveness domain. The overall mean score of all the domains was 4.20 with standard deviation of 0.51. Overall majority (80.8%) of respondents rated the overall service quality as good/ very good. After linear regression, the assurance domain was the most important predictor of the overall perceived service quality (p< 0.001). CONCLUSION: The overall perceived service quality was good. The major deficiencies were in the responsiveness domain and especially the waiting time. The hospital management should implement measures to improve the responsiveness of services by ensuring prompt delivery of services. PMID- 26834923 TI - [Metastatic angiosarcoma of the thigh: rare complication of lymphedema]. PMID- 26834922 TI - [Osteogenesis imperfecta: about four cases in Ouagadougou (Burkina Faso)]. PMID- 26834924 TI - Teeth syndrome: diagnosis, complications and management. AB - Teeth syndrome or fight bite is a specific entity in hand surgery that is little known. It includes infectious complications of the hand following a fist against the teeth. Neglected or misdiagnosed this injury frequently leads to serious complications that could compromise the function of the hand. A retrospective study was performed on 20 patients treated for teeth syndrome at our department, during a period of 12 years (January 2003 to April 2015). All young adults with a mean age of 28 years and a significant male predominance. The dominant side was involved in 15 patients. Lesions were divided into 4 cases of simple dorsal wounds facing the MP joint, 8 cases of dorsal hand cellulitis, and 8 cases of arthritis and osteoarthritis of the metacarpophalangeal (MP) joint of the long fingers. The index was the most affected finger. Treatment consisted in debridement of necrotic tissues, stabilization with external fixation for arthritis, skin reconstruction was performed secondarily. Result was assessed as good in 60% of cases. Clenched fist injuries to the mouth (teeth syndrome or fight bite) are known as being the worst human bites. Usually treated as minor injuries, without realizing a breach of the joint capsule, a lesion of the extensor tendon, or a contamination by oral flora. Any patient with a wound near the joint of the hand and was involved in a fight, need an appropriate evaluation and a specialized treatment to avoid serious complications. PMID- 26834925 TI - [Moroccan experience on neglected goiters in humanitarian mission in Guinea Bissau: About four observations]. PMID- 26834926 TI - [Uterine adenomyosis, clinical and therapeutic study: about 87 cases]. PMID- 26834927 TI - [Fibromatosis colli or congenital torticollis: diagnosis and management about two cases]. PMID- 26834928 TI - Systemic sarcoidosis complicated of acute renal failure: about 12 cases. AB - The sarcoidosis is a systemic granulomatosis affecting most frequently the lungs and the mediastinum. An acute renal failure reveals exceptionally this disease. It's a retrospective study implicating 12 cases of sarcoidosis complicated of acute renal failure. The aim of this study is to determine epidemiological, clinical, biological and histological profile in these cases and then to indicate the interest to consider the diagnosis of sarcoidosis in cases of unexplained renal failure. Extra-renal complications, therapeutic modalities and the outcome were determined in all patients. Our series involved 12 women with an average age of 40 years. Biological investigations showed an abnormal normocalcemia in 7 cases, a hypercalcemia in 5 cases, a hypercalciuria in 10 cases and polyclonal hypergammaglobulinemia in 7 cases. An acute renal failure was found in all patients with a median creatinin of 520 umol/L. For all patients, the renal echography was normal however, the kidney biopsy showed tubulo-interstitial nephritis. The extra-renal signs highlighting pulmonary interstitial syndrome in 5 cases, a sicca syndrome in 4 cases, mediastinal lymph nodes in 2 cases, a lymphocytic alveolitis in 3 cases, an anterior granulomatous uveitis in 2 cases and a polyarthritis in 5 cases. Five patients benefited of hemodialysis. The treatment consisted of corticosteroid in all cases. The follow up was marked by complete resolution of clinical and biological signs. The diagnosis of renal sarcoidosis must be done quickly to prevent renal failure. PMID- 26834931 TI - PEACE Time. PMID- 26834930 TI - Epidemiology and outcome of articular complications in adult onset Still's disease. AB - The adult onset Still's disease is a rare inflammatory pathology of unknown pathogeny. The clinical features are variable. The diagnosis is difficult since exclusion of infectious, systemic and tumoral pathologies should be done. The articular complications are frequent and can be revelatory of this pathology. The articular prognosis depends on the diagnosis delay and the treatment efficiency. Our study aims to analyze different aspects of articular manifestations complicating adult onset Still disease to define epidemiological, clinical and evolving characteristics of these complications. It was a cross-sectional study concerning 18 cases of adult onset Still disease diagnosed from 1990 to 2014 in the internal medicine A department of Charles Nicolle Hospital in Tunis, meeting Yamaguchi criteria. We identified clinical, radiological, evolving and therapeutic profile of the articular manifestations occurred in these patients. There were 11 women and 7 men. The average age was 27 years. The arthralgias were reported in all cases; while, the arthritis interested thirteen patients. A hand deformation was found in four patients. A wrist ankylosis was noted in one case and a flexion elbow in one patient. The Standard articular radiographs were normal in ten cases. The treatment associated essentially non-steroidal anti inflammatory and/or corticosteroids and/or methotrexate. Concerning the evolving profile, the monocyclic form was present in 25% of the cases, the intermittent form in 40% and the chronic articular form in 35% of our patients. The adult onset Still's disease is rare and heterogeneous. The articular disturbances are frequent and have various outcomes. PMID- 26834929 TI - Motivations and concerns about adolescent tuberculosis vaccine trial participation in rural Uganda: a qualitative study. AB - INTRODUCTION: Research is being carried out to develop and test new potentially more effective tuberculosis vaccines. Among the vaccines being developed are those that target adolescents. This study explored the stakeholders' perceptions about adolescent participation in a hypothetical tuberculosis vaccine trial in Ugandan adolescents. METHODS: Focus group discussions with adolescents, parents of infants and adolescents, and key informant interviews with community leaders and traditional healers were conducted. RESULTS: The majority of the respondents expressed potential willingness to allow their children participate in a tuberculosis vaccine trial. Main motivations for potential participation would be being able to learn about health-related issues. Hesitations included the notion that trial participation would distract the youths from their studies, fear of possible side effects of an investigational product, and potential for being sexually exploited by researchers. In addition, bad experiences from participation in previous research and doubts about the importance of research were mentioned. Suggested ways to motivate participation included: improved clarity on study purpose, risks, benefits and better scheduling of study procedures to minimize disruption to participants' academic schedules. CONCLUSION: Findings from this study suggest that the community is open to potential participation of adolescents in a tuberculosis vaccine trial. However, there is a need to communicate more effectively with the community about the purpose of the trial and its effects, including safety data, in a low-literacy, readily understood format. This raises a challenge to researchers, who cannot know all the potential effects of a trial product before it is tested. PMID- 26834932 TI - Cost of Treatment for Relapsed/Refractory Multiple Myeloma. PMID- 26834933 TI - Anticipated Impact of Generic Imatinib Market Entry on the Costs of Tyrosine Kinase Inhibitors. AB - BACKGROUND: Imatinib was the first BCR-ABL tyrosine kinase inhibitor (TKI) approved in the United States for the treatment of patients with chronic myelogenous leukemia and is currently the most prescribed TKI. The impending loss of patent exclusivity for imatinib has the potential to reduce costs for payers. OBJECTIVE: The primary objectives of this study were to estimate the economic impact of the loss of patent exclusivity for branded imatinib and to calculate the relative impact of requiring prior authorization (PA) for the use of generic imatinib before a branded TKI. The secondary objective was to evaluate the potential relative cost impact of using a preferred branded TKI in addition to the PA requirement for generic imatinib before a branded TKI. METHODS: A Microsoft Excel-based model was developed from the perspective of a US payer (commercial and Medicare) for a 2-year period. Data on utilization, patient out of-pocket cost, and market share were obtained from an analysis of Truven Health MarketScan claims. It was assumed that the cost of generic imatinib would be 47.8% of the price of branded imatinib. It was assumed that 70% of patients receiving branded imatinib would shift to generic imatinib in year 1, and 95% would shift in year 2 after loss of patent exclusivity. Formulary management could be applied through PA requiring the use of generic imatinib before a branded TKI for patients newly prescribed TKI therapy. It was assumed that 74% of PA requests would be approved, and that the administrative cost of each would be $20. RESULTS: In a hypothetical 1 million member commercial plan, the loss of patent exclusivity for branded imatinib produced cost-savings of $6.8 million during 2 years, or 28.8% of the total pharmacy spending on the TKI class. The savings were even greater in a 1 million member Medicare plan, at $22.9 million (28.8%). Formulary management reduced incremental TKI spending by 1.1% and 2.2% for the commercial and Medicare plans, respectively. CONCLUSIONS: In the absence of formulary management beyond generic substitution, the loss of patent exclusivity for branded imatinib is expected to reduce total pharmacy spending on TKIs by nearly 33% during 2 years. Given the small number of newly treated patients, formulary management of the TKI class through restricted access to branded imatinib, with or without a preferred branded TKI, has limited potential for incremental cost-savings. PMID- 26834934 TI - The PCSK9 Inhibitors: A Novel Therapeutic Target Enters Clinical Practice. AB - There is a critical need for alternative, potent agents that can reduce low density lipoprotein cholesterol (LDL-C) levels in patients with heterozygous familial hyperlipidemia and statin intolerance and those not reaching lipid lowering treatment goals who are at high risk for cardiovascular (CV) events. The first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor was approved in July 2015 by the US Food and Drug Administration as an adjunct to diet and maximally tolerated statin therapy for treatment of adults with heterozygous familial hyperlipidemia or clinical atherosclerotic CV disease, who require additional lowering of LDL-C levels. In clinical trials, PCSK9 inhibitors have been shown to reduce LDL-C levels by as much as 60% to 70% when administered as monotherapy or as an add-on treatment to statins and other lipid-lowering therapies. In studies of PCSK9 genetic mutations, loss of function in the PCSK9 allele was associated with a relative decrease of 88% in the risk for atherosclerotic CV events during 15 years of patient follow-up. The use of PCSK9 inhibitors may eventually support the LDL-C hypothesis that the lower the LDL-C level, the lower the CV risk. Although some recent clinical practice guidelines have deemphasized the importance of numeric LDL-C targets, many clinicians are reluctant to discard them, and this position is supported by recent clinical evidence. We eagerly await the results of the ODYSSEY, FOURIER, and SPIRE clinical outcome trials, which we anticipate will provide further validation that "lower is better" with respect to reducing LDL-C levels and improving clinical outcomes. PMID- 26834935 TI - Employers Engaged in Benefit Design Innovation: Long-Term Trends in a 2015 National Survey. PMID- 26834936 TI - Novel Adherence Measures for Infusible Therapeutic Agents Indicated for Rheumatoid Arthritis. AB - BACKGROUND: Published studies on adherence to biologic medications show that many types of calculation methods are used. However, infused biologics are not well suited to typical measures of adherence, such as proportion of days covered. OBJECTIVE: To construct and assess 7 novel adherence measures potentially applicable to infusible biologic agents and compare outcomes for 2 infusible biologics used for the treatment of patients with rheumatoid arthritis (RA). METHODS: Adults (aged >=18 years) diagnosed with RA (ie, 2 or more 714.x claims) who received >=24 months of continuous medical and pharmacy eligibility and who started taking abatacept or infliximab therapy were selected from a large commercial insurer database of medical and pharmacy claims. The 7 new adherence measures included cumulative amount of time with a refill gap >=20% (CG20) beyond the expected infusion interval, cumulative time off treatment, days of uninterrupted use (DoUU), observed versus expected refill ratio (OvERR), repeated observations of underuse (RoUU), variance in time between infusions, and time to discontinuation (TTD). Mean observed infusion intervals were calculated and served as a reference measure of adherence. RESULTS: The mean maintenance intervals approximated recommended guidelines. The mean observed infusion interval for abatacept recipients was 33 days (recommended, 28 days); it was 53 days (recommended, 56 days) for patients receiving infliximab. Three measures demonstrated a significant positive relationship to the mean observed infusion interval-CG20 (r = .258), DoUU (r = .212), and TTD (r = .081; P <.05). OvERR (r = -.072) and RoUU (r = -.189; P <.05) showed significant negative correlations. Real-world comparisons showed that adherence was significantly (P <.001) greater for the infliximab group according to most measures. CONCLUSION: New measures of adherence correlate significantly with mean maintenance intervals. Future studies should examine relationships between these adherence measures and clinically relevant end points and/or cost outcomes to determine their predictive utility. Alternative methods of reporting adherence may have greater clinical significance than traditional measures. PMID- 26834937 TI - Agent-based computational model of the prevalence of gonococcal infections after the implementation of HIV pre-exposure prophylaxis guidelines. AB - Recently, the first comprehensive guidelines were published for pre-exposure prophylaxis (PrEP) for the prevention of HIV infection in populations with substantial risk of infection. Guidelines include a daily regimen of emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) as well as condom usage during sexual activity. The relationship between the TDF/FTC intake regimen and condom usage is not yet fully understood. If men who have sex with men (MSM,) engage in high-risk sexual activities without using condoms when prescribed TDF/FTC they might be at an increased risk for other sexually transmitted diseases (STD). Our study focuses on the possible occurrence of behavioral changes among MSM in the United States over time with regard to condom usage. In particular, we were interested in creating a model of how increased uptake of TDF/FTC might cause a decline in condom usage, causing significant increases in non-HIV STD incidence, using gonococcal infection incidence as a biological endpoint. We used the agent-based modeling software NetLogo, building upon an existing model of HIV infection. We found no significant evidence for increased gonorrhea prevalence due to increased PrEP usage at any level of sample-wide usage, with a range of 0-90% PrEP usage. However, we did find significant evidence for decreased prevalence of HIV, with a maximal effect being reached when 5% to 10% of the MSM population used PrEP. Our findings appear to indicate that attitudes of aversion, within the medical community, toward the promotion of PrEP due to the potential risk of increased STD transmission are unfounded. PMID- 26834938 TI - Data Lakes and Data Visualization: An Innovative Approach to Address the Challenges of Access to Health Care in Mississippi. AB - BACKGROUND: There are a variety of challenges to developing strategies to improve access to health care, but access to data is critical for effective evidence based decision-making. Many agencies and organizations throughout Mississippi have been collecting quality health data for many years. However, those data have historically resided in data silos and have not been readily shared. A strategy was developed to build and coordinate infrastructure, capacity, tools, and resources to facilitate health workforce and population health planning throughout the state. OBJECTIVE: Realizing data as the foundation upon which to build, the primary objective was to develop the capacity to collect, store, maintain, visualize, and analyze data from a variety of disparate sources -- with the ultimate goal of improving access to health care. Specific aims were to: 1) build a centralized data repository and scalable informatics platform, 2) develop a data management solution for this platform and then, 3) derive value from this platform by facilitating data visualization and analysis. METHODS: A managed data lake was designed and constructed for health data from disparate sources throughout the state of Mississippi. A data management application was developed to log and track all data sources, maps and geographies, and data marts. With this informatics platform as a foundation, a variety of tools are used to visualize and analyze data. To illustrate, a web mapping application was developed to examine the health workforce geographically and attractive data visualizations and dynamic dashboards were created to facilitate health planning and research. RESULTS: Samples of data visualizations that aim to inform health planners and policymakers are presented. Many agencies and organizations throughout the state benefit from this platform. CONCLUSION: The overarching goal is that by providing timely, reliable information to stakeholders, Mississippians in general will experience improved access to quality care. PMID- 26834939 TI - Cross-Disciplinary Consultancy to Bridge Public Health Technical Needs and Analytic Developers: Asyndromic Surveillance Use Case. AB - INTRODUCTION: We document a funded effort to bridge the gap between constrained scientific challenges of public health surveillance and methodologies from academia and industry. Component tasks are the collection of epidemiologists' use case problems, multidisciplinary consultancies to refine them, and dissemination of problem requirements and shareable datasets. We describe an initial use case and consultancy as a concrete example and challenge to developers. MATERIALS AND METHODS: Supported by the Defense Threat Reduction Agency Biosurveillance Ecosystem project, the International Society for Disease Surveillance formed an advisory group to select tractable use case problems and convene inter disciplinary consultancies to translate analytic needs into well-defined problems and to promote development of applicable solution methods. The initial consultancy's focus was a problem originated by the North Carolina Department of Health and its NC DETECT surveillance system: Derive a method for detection of patient record clusters worthy of follow-up based on free-text chief complaints and without syndromic classification. RESULTS: Direct communication between public health problem owners and analytic developers was informative to both groups and constructive for the solution development process. The consultancy achieved refinement of the asyndromic detection challenge and of solution requirements. Participants summarized and evaluated solution approaches and discussed dissemination and collaboration strategies. PRACTICE IMPLICATIONS: A solution meeting the specification of the use case described above could improve human monitoring efficiency with expedited warning of events requiring follow-up, including otherwise overlooked events with no syndromic indicators. This approach can remove obstacles to collaboration with efficient, minimal data-sharing and without costly overhead. PMID- 26834940 TI - Editorial OJPHI Vol 7, No 3 (2015). PMID- 26834941 TI - Magnetic resonance imaging differential diagnosis of brainstem lesions in children. AB - Differential diagnosis of brainstem lesions, either isolated or in association with cerebellar and supra-tentorial lesions, can be challenging. Knowledge of the structural organization is crucial for the differential diagnosis and establishment of prognosis of pathologies with involvement of the brainstem. Familiarity with the location of the lesions in the brainstem is essential, especially in the pediatric population. Magnetic resonance imaging (MRI) is the most sensitive and specific imaging technique for diagnosing disorders of the posterior fossa and, particularly, the brainstem. High magnetic static field MRI allows detailed visualization of the morphology, signal intensity and metabolic content of the brainstem nuclei, together with visualization of the normal development and myelination. In this pictorial essay we review the brainstem pathology in pediatric patients and consider the MR imaging patterns that may help the radiologist to differentiate among vascular, toxico-metabolic, infective inflammatory, degenerative and neoplastic processes. Helpful MR tips can guide the differential diagnosis: These include the location and morphology of lesions, the brainstem vascularization territories, gray and white matter distribution and tissue selective vulnerability. PMID- 26834945 TI - Leakage-Penumbra effect in intensity modulated radiation therapy step-and-shoot dose delivery. AB - AIM: To study the leakage-penumbra (LP) effect with a proposed correction method for the step-and-shoot intensity modulated radiation therapy (IMRT). METHODS: Leakage-penumbra dose profiles from 10 randomly selected prostate IMRT plans were studied. The IMRT plans were delivered by a Varian 21 EX linear accelerator equipped with a 120-leaf multileaf collimator (MLC). For each treatment plan created by the Pinnacle(3) treatment planning system, a 3-dimensional LP dose distribution generated by 5 coplanar photon beams, starting from 0(o) with equal separation of 72(o), was investigated. For each photon beam used in the step-and shoot IMRT plans, the first beam segment was set to have the largest area in the MLC leaf-sequencing, and was equal to the planning target volume (PTV). The overshoot effect (OSE) and the segment positional errors were measured using a solid water phantom with Kodak (TL and X-OMAT V) radiographic films. Film dosimetric analysis and calibration were carried out using a film scanner (Vidar VXR-16). The LP dose profiles were determined by eliminating the OSE and segment positional errors with specific individual irradiations. RESULTS: A non-uniformly distributed leaf LP dose ranging from 3% to 5% of the beam dose was measured in clinical IMRT beams. An overdose at the gap between neighboring segments, represented as dose peaks of up to 10% of the total BP, was measured. The LP effect increased the dose to the PTV and surrounding critical tissues. In addition, the effect depends on the number of beams and segments for each beam. Segment positional error was less than the maximum tolerance of 1 mm under a dose rate of 600 monitor units per minute in the treatment plans. The OSE varying with the dose rate was observed in all photon beams, and the effect increased from 1 to 1.3 Gy per treatment of the rectal intersection. As the dosimetric impacts from the LP effect and OSE may increase the rectal post-radiation effects, a correction of LP was proposed and demonstrated for the central beam profile for one of the planned beams. CONCLUSION: We concluded that the measured dosimetric impact of the LP dose inaccuracy from photon beam segment in step-and-shoot IMRT can be corrected. PMID- 26834946 TI - Correlation between thoracic aorta 18F-natrium fluoride uptake and cardiovascular risk. AB - AIM: To investigating the relationship between thoracic and cardiac (18)F-Natrium Fluoride (18F-NaF) uptake, as a marker of ongoing calcification and cardiovascular risk factors. METHODS: Seventy-eight patients (44 females, mean age 63, range 44-83) underwent whole body 18F-NaF positron emission tomography/computed tomography. Cardiovascular risk (CVR) was used to divide these patients in three categories: Low (LR), medium (MR) and high risk (HR). 18F NaF uptake was measured by manually drawing volumes of interest on the ascending aorta, on the aortic arch, on the descending aorta and on the myocardium; average standardized uptake value was normalized for blood-pool, to obtain target-to background ratio (TBR). Values from the three aortic segments were then averaged to obtain an index of the whole thoracic aorta. RESULTS: A significant difference in whole thoracic aorta TBR was detected between HR and LR (1.84 +/- 0.76 vs 1.07 +/- 0.3, P < 0.001), but also between MR and HR-LR (1.4 +/- 0.4, P < 0.02 and P < 0.01, respectively). Significance of this TBR stratification strongly varied among thoracic aorta subsegments and the lowest P values were reached in the descending aorta (P < 0.01). Myocardial uptake provided an effective CVR classes stratification (P < 0.001).Correlation between TBR and CVR was appreciable when the whole thoracic aorta was considered (R = 0.67), but it peaked when correlating the descending thoracic segment (R = 0.75), in comparison with the aortic arch and the ascending segment (R = 0.55 and 0.53, respectively). CONCLUSION: Fluoride uptake within the thoracic aorta wall effectively depicts patients' risk class and correlates with cardiovascular risk. Descending aorta is the most effective in CVR determination. PMID- 26834943 TI - Review on the applications of ultrasonography in dentomaxillofacial region. AB - Use of ultrasonography (US) in dentomaxillofacial region became popular in recent years owing to increasing radiation dose concerns and economic limitations. It helps to visualize fine detail of the surface structure of the oral and maxillofacial tissues without ionizing radiation. In diagnostic ultrasound, high frequency sound waves are transmitted into the body by a transducer and echoes from tissue interface are detected and displayed on a screen. Sound waves are emitted via piezoelectric crystals from the ultrasound transducer. US technique can be used in dentomaxillofacial region for the examination of bone and superficial soft tissue, detection of major salivary gland lesions, temporomandibular joint imaging, assessment of fractures and vascular lesions, lymph node examination, measurement of the thickness of muscles and visualization of vessels of the neck. It has the potential to be used in the evaluation of periapical lesions and follow up of periapical bone healing. Also, it may be used for the evaluation of periodontal pocket depth and for the determination of gingival thickness before dental implantology. PMID- 26834942 TI - Diffusion-weighted magnetic resonance imaging in cancer: Reported apparent diffusion coefficients, in-vitro and in-vivo reproducibility. AB - There is considerable disparity in the published apparent diffusion coefficient (ADC) values across different anatomies. Institutions are increasingly assessing repeatability and reproducibility of the derived ADC to determine its variation, which could potentially be used as an indicator in determining tumour aggressiveness or assessing tumour response. In this manuscript, a review of selected articles published to date in healthy extra-cranial body diffusion weighted magnetic resonance imaging is presented, detailing reported ADC values and discussing their variation across different studies. In total 115 studies were selected including 28 for liver parenchyma, 15 for kidney (renal parenchyma), 14 for spleen, 13 for pancreatic body, 6 for gallbladder, 13 for prostate, 13 for uterus (endometrium, myometrium, cervix) and 13 for fibroglandular breast tissue. Median ADC values in selected studies were found to be 1.28 * 10(-3) mm(2)/s in liver, 1.94 * 10(-3) mm(2)/s in kidney, 1.60 * 10(-3) mm(2)/s in pancreatic body, 0.85 * 10(-3) mm(2)/s in spleen, 2.73 * 10(-3) mm(2)/s in gallbladder, 1.64 * 10(-3) mm(2)/s and 1.31 * 10(-3) mm(2)/s in prostate peripheral zone and central gland respectively (combined median value of 1.54*10(-3) mm(2)/s), 1.44 * 10(-3) mm(2)/s in endometrium, 1.53 * 10(-3) mm(2)/s in myometrium, 1.71 * 10(-3) mm(2)/s in cervix and 1.92 * 10(-3) mm(2)/s in breast. In addition, six phantom studies and thirteen in vivo studies were summarized to compare repeatability and reproducibility of the measured ADC. All selected phantom studies demonstrated lower intra-scanner and inter-scanner variation compared to in vivo studies. Based on the findings of this manuscript, it is recommended that protocols need to be optimised for the body part studied and that system-induced variability must be established using a standardized phantom in any clinical study. Reproducibility of the measured ADC must also be assessed in a volunteer population, as variations are far more significant in vivo compared with phantom studies. PMID- 26834947 TI - Texture analysis on parametric maps derived from dynamic contrast-enhanced magnetic resonance imaging in head and neck cancer. AB - AIM: To investigate the merits of texture analysis on parametric maps derived from pharmacokinetic modeling with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as imaging biomarkers for the prediction of treatment response in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: In this retrospective study, 19 HNSCC patients underwent pre- and intra-treatment DCE-MRI scans at a 1.5T MRI scanner. All patients had chemo-radiation treatment. Pharmacokinetic modeling was performed on the acquired DCE-MRI images, generating maps of volume transfer rate (K(trans)) and volume fraction of the extravascular extracellular space (ve). Image texture analysis was then employed on maps of K(trans) and ve, generating two texture measures: Energy (E) and homogeneity. RESULTS: No significant changes were found for the mean and standard deviation for K(trans) and ve between pre- and intra-treatment (P > 0.09). Texture analysis revealed that the imaging biomarker E of ve was significantly higher in intra treatment scans, relative to pretreatment scans (P < 0.04). CONCLUSION: Chemo radiation treatment in HNSCC significantly reduces the heterogeneity of tumors. PMID- 26834944 TI - General review of magnetic resonance elastography. AB - Magnetic resonance elastography (MRE) is an innovative imaging technique for the non-invasive quantification of the biomechanical properties of soft tissues via the direct visualization of propagating shear waves in vivo using a modified phase-contrast magnetic resonance imaging (MRI) sequence. Fundamentally, MRE employs the same physical property that physicians utilize when performing manual palpation - that healthy and diseased tissues can be differentiated on the basis of widely differing mechanical stiffness. By performing "virtual palpation", MRE is able to provide information that is beyond the capabilities of conventional morphologic imaging modalities. In an era of increasing adoption of multi parametric imaging approaches for solving complex problems, MRE can be seamlessly incorporated into a standard MRI examination to provide a rapid, reliable and comprehensive imaging evaluation at a single patient appointment. Originally described by the Mayo Clinic in 1995, the technique represents the most accurate non-invasive method for the detection and staging of liver fibrosis and is currently performed in more than 100 centers worldwide. In this general review, the mechanical properties of soft tissues, principles of MRE, clinical applications of MRE in the liver and beyond, and limitations and future directions of this discipline -are discussed. Selected diagrams and images are provided for illustration. PMID- 26834948 TI - Evaluation of variations in sinonasal region with computed tomography. AB - AIM: To investigate the frequency of anatomical variations in sinonasal region and association of these variations with mucosal diseases. METHODS: The study included 400 cases (191 female and 209 male) who were considered to have preliminary diagnoses of sinonasal pathology and who had paranasal sinus computed tomography (CT) examination in axial plane. Reformatted CT images were studied in all planes. RESULTS: Age range of the patients was 20-83 (mean 40.26 +/- 14.85). Most commonly detected anatomical variation was Agger nasi cell (74.8%). There was a significant association between clinoid process pneumatization and protrusion of internal carotid arteries and optic nerves into sphenoid sinus (P < 0.001). Besides, the relationships between pterygoid process pneumatization and protrusion of vidian nerve into sphenoid sinus, and between pneumatization of large sphenoid wing and protrusion of maxillary nerves into sphenoid sinus were also significant (P < 0.001). Uncinate bulla and giant ethmoid bulla were found to be significantly associated with sinonasal mucosal diseases (P = 0.004 and P = 0.002, respectively). CONCLUSION: Sinonasal region has a great number of variations, and some of them have been determined to be associated with sinonasal mucosal disease. It is necessary to know that some of these variations are associated with protrusion of significant structures such as carotid artery or optic nerve into the sinus and care should be observed in surgeries on patients carrying these variations. PMID- 26834949 TI - Incremental value of magnetic resonance neurography of Lumbosacral plexus over non-contributory lumbar spine magnetic resonance imaging in radiculopathy: A prospective study. AB - AIM: To test the incremental value of 3T magnetic resonance neurography (MRN) in a series of unilateral radiculopathy patients with non-contributory magnetic resonance imaging (MRI). METHODS: Ten subjects (3 men, 7 women; mean age 54 year and range 22-74 year) with unilateral lumbar radiculopathy and with previous non contributory lumbar spine MRI underwent lumbosacral (LS) plexus MRN over a period of one year. Lumbar spine MRI performed as part of the MRN LS protocol as well as bilateral L4-S1 nerves, sciatic, femoral and lateral femoral cutaneous nerves were evaluated in each subject for neuropathy findings on both anatomic (nerve signal, course and caliber alterations) and diffusion tensor imaging (DTI) tensor maps (nerve signal and caliber alterations). Minimum fractional anisotropy (FA) and mean apparent diffusion coeffcient (ADC) of L4-S2 nerve roots, sciatic and femoral nerves were recorded. RESULTS: All anatomic studies and 80% of DTI imaging received a good-excellent imaging quality grading. In a blinded evaluation, all 10 examinations demonstrated neural and/or neuromuscular abnormality corresponding to the site of radiculopathy. A number of contributory neuropathy findings including double crush syndrome were observed. On DTI tensor maps, nerve signal and caliber alterations were more conspicuous. Although individual differences were observed among neuropathic appearing nerve (lower FA and increased ADC) as compared to its contralateral counterpart, there were no significant mean differences on statistical comparison of LS plexus nerves, femoral and sciatic nerves (P > 0.05). CONCLUSION: MRN of LS plexus is useful modality for the evaluation of patients with non-contributory MRI of lumbar spine as it can incrementally delineate the etiology and provide direct objective and non-invasive evidence of neuromuscular pathology. PMID- 26834950 TI - Sonodelivery Facilitates Sustained Luciferase Expression from an Episomal Vector in Skeletal Muscle. AB - Successful gene delivery to skeletal muscle is a desirable goal, not only for treating muscle diseases, but also for immunization, treatment of metabolic disorders, and/or delivering gene expression that can treat systemic conditions, such as bone metastatic cancer, for example. Although naked DNA uptake into skeletal muscle is possible, it is largely inefficient in the absence of additional chemical or physical delivery methods. We describe a system for delivery of non-viral or plasmid DNA to skeletal muscle using ultrasound-assisted sonoporation of a nanoplex combining plasmid DNA and a branched polymer based on poly(cyclooctene-graft-oligopeptide). The materials and methods described herein promise to advance the field of sonodelivery and of gene delivery to muscle for therapeutic applications since a simple system is presented that enables long term gene expression in vivo with the promise of a minimal inflammatory gene expression profile. PMID- 26834951 TI - Monitoring minimal residual disease in acute myeloid leukaemia: a review of the current evolving strategies. AB - Several disease-monitoring techniques are available for the physician treating acute myeloid leukaemia (AML). Besides immunohistochemistry assisted light microscopy, the past 20 years have seen the development and preclinical perfection of a number of techniques, most notably quantitative polymerase chain reaction (PCR) and multicolor flow cytometry. Late additions to the group of applicable assays include next generation sequencing and digital PCR. In this review the principles of use of these modalities at three different time points during the AML disease course are discussed, namely at the time of treatment evaluation, pretransplantation and postconsolidation. The drawbacks and pitfalls of each different technique are delineated. The evidence or lack of evidence for minimal residual disease guided treatment decisions is discussed. Lastly, future strategies in the MRD field are suggested and commented upon. PMID- 26834953 TI - Targeting the leukemia-stroma interaction in acute myeloid leukemia: rationale and latest evidence. AB - The concept of 'niche' has become a focus of attention in hematologic malignancies including acute myeloid leukemia (AML). Similar to normal hematopoietic stem cells, AML cells interact both anatomically and functionally with the stroma within the marrow microenvironment. These interactions have a critical role in the development, progression, and relapse of AML. Chemotherapy resistance is another feature that is at least partially related to AML-stroma interactions. The evidence for safety and efficacy of agents targeting AML-niche interactions is currently limited to preclinical and early phase clinical studies. Examples include CXCR4 inhibitors, hypoxia-inducible agents, and adhesion molecule inhibitors. Agents that target AML-stroma interactions differ from mutation-specific approaches that tend to be limited due to within individual and between-individual genetic heterogeneity. These agents may be used alone or as chemosensitizers in AML. This novel and rapidly advancing strategy is likely to become an important part of our armamentarium of anti-leukemia treatments in the near future. PMID- 26834952 TI - Novel immunotherapeutic approaches for the treatment of acute leukemia (myeloid and lymphoblastic). AB - There have been major advances in our understanding of the multiple interactions between malignant cells and the innate and adaptive immune system. While the attention of immunologists has hitherto focused on solid tumors, the specific immunobiology of acute leukemias is now becoming defined. These discoveries have pointed the way to immune interventions building on the established graft-versus leukemia (GVL) effect from hematopoietic stem-cell transplant (HSCT) and extending immunotherapy beyond HSCT to individuals with acute leukemia with a diversity of immune manipulations early in the course of the leukemia. At present, clinical results are in their infancy. In the coming years larger studies will better define the place of immunotherapy in the management of acute leukemias and lead to treatment approaches that combine conventional chemotherapy, immunotherapy and HSCT to achieve durable cures. PMID- 26834954 TI - Current challenges and novel treatment strategies in double hit lymphomas. AB - High-grade B-cell lymphomas with recurrent chromosomal break points have been termed 'double hit lymphoma' (DHL). The most commonly seen DHL is diffuse large B cell lymphoma (DLBCL) with t(14;18) and t(8;14) or t(8;22) resulting in overexpression of BCL2 and MYC, respectively. The increased proliferation due to MYC overexpression, without the ability for an apoptotic brake as a result of BCL2 overexpression, results in 'the perfect storm of oncogenesis'. Thus this disease presents a number of diagnostic and therapeutic challenges for the hematologist. The first and foremost challenge is to recognize the DHL. As different morphological entities can be affected it is incumbent on pathologists and clinicians to maintain a high index of suspicion especially in disease that appears unusually aggressive or refractory to therapy. Diagnosis by fluorescence in situ hybridization (FISH) is a sensitive and specific method for detection of the disease but is time-consuming and expensive. While detection by immunohistochemistry (IHC) is sensitive and correlates with survival, standardized methods for this are not widely agreed upon. The second and equally important challenge in DHL is optimizing clinical outcome in a group of patients for whom the prognosis is widely regarded as poor. While improvements have been achieved by dose escalating standard chemotherapeutic regimens, many patients continue to do badly. Furthermore as a disease of aging many patients are unsuitable for dose-intensive chemotherapy regimens. There are now multiple novel targeted agents in various stages of clinical development that offer hope for better outcomes without undue toxicity. Among the most exciting of these developments include specific inhibitors of both BCL2 and MYC. PMID- 26834955 TI - Response to the NCEPOD report: development of a care bundle for patients admitted with decompensated cirrhosis-the first 24 h. AB - Recently, there has been a significant increase in the prevalence of chronic liver disease in the UK, and as a result, hospital admissions and deaths due to liver disease have also increased. The 2013 National Confidential Enquiry into Patient Outcome and Death (NCEPOD) of patients with alcohol-related liver disease (ARLD) found that less than half the number of patients who died from ARLD received 'good care', and avoidable deaths were identified. In order to improve the care of patients admitted with ARLD, the NCEPOD report recommended that a 'toolkit' for the acute management of patients admitted with decompensated ARLD be developed and made widely available. As a result, we have developed a 'care bundle' for patients admitted with decompensated cirrhosis (of all aetiologies) to ensure that effective evidence-based treatments are delivered within the first 24 h. This care bundle provides a checklist to ensure that all appropriate investigations are undertaken when a patient with decompensated cirrhosis presents and provides clinicians with clear guidance on the initial management of alcohol withdrawal, infection, acute kidney injury, gastrointestinal bleeding and encephalopathy. The first 24 h are particularly important, as early intervention can reduce mortality and shorten hospital stay, and specialist gastroenterology/liver advice is not always available during this period. This review will discuss the care bundle and the evidence base behind the treatment recommendations made. PMID- 26834956 TI - Incidence of metachronous visible lesions in patients referred for radiofrequency ablation (RFA) therapy for early Barrett's neoplasia: a single-centre experience. AB - OBJECTIVE: Evaluate the incidence of metachronous visible lesions (VLs) in patients referred for radiofrequency ablation (RFA) for early Barrett's neoplasia. DESIGN: This study was conducted as part of the service evaluation audit. SETTING: Tertiary referral centre. PATIENTS: All patients with dysplastic Barrett's oesophagus referred for RFA were included for analysis. White light high-resolution endoscopy (HRE), autofluorescence imaging and narrow band imaging were sequentially performed. Endoscopic mucosal resection (EMR) was performed for all VL. Three to six months after EMR, all patients underwent initial RFA and then repeat RFA procedures at three monthly intervals. INTERVENTIONS: All endoscopy reports and final staging by EMR/surgery were evaluated and included for analysis. RESULTS: Fifty patients were analysed; median age 73 years, 84% men. 38/50 patients (76%) had a previous EMR due to the presence of VL before referred for ablation; twelve patients had no previous treatment. In total, 151 ablation procedures were performed, median per patient 2.68. Twenty metachronous VL were identified in 14 patients before the first ablation or during the RFA protocol; incidence was 28%. All metachronous lesions were successfully resected by EMR. Upstaging after rescue EMR compared with the initial histology was observed in four patients (28%). CONCLUSIONS: In total, 28% of patients enrolled in the RFA programme were diagnosed to have metachronous lesions. This high incidence rate highlights the importance of a meticulous examination to identify and resect any VL before every ablation session. RFA treatment for early Barrett's neoplasia should be performed in tertiary referral centres with HRE and EMR facilities and expertise. PMID- 26834957 TI - Can a theoretical framework help to embed alcohol screening and brief interventions in an endoscopy day-unit? AB - INTRODUCTION AND AIMS: The National Institute for Health Care and Excellence recommend that alcohol screening and brief intervention (ASBI) should be routinely implemented in secondary care. This study used theoretical frameworks to understand how health professionals can be supported to adapt their behaviour and clinical practice. DESIGN AND METHODS: Staff training and support was conducted using theoretical frameworks. A 12-week study, delivering ASBI was carried out as part of routine practice in an endoscopy day-unit. Anonymised patient data were collected using the Alcohol Use Disorders Identification Tool (AUDIT) and whether patients received a brief intervention. Staff completed the Shortened Alcohol and Alcohol Problems Perceptions Questionnaire at three time points and took part in a focus group both pre and post study. RESULTS: For staff, levels or role adequacy, role legitimacy, motivation to discuss alcohol, security in their role, job satisfaction and commitment to working with patients who drink increased during the time of the study. 1598 individual patients were seen in the department in the timeframe. Of these, 1180 patients were approached (74%); 18% (n=207) of patients were AUDIT positive. DISCUSSION: This study has shown that it is possible to reach a high number of patients in a busy hospital out-patient department and deliver ASBI by working with staff using theoretical frameworks for training. Embedding evidence-based public health interventions into routine clinical environments is complex. The social system in which professionals operate requires consideration alongside individual professionals' real and perceived barriers and facilitators to change. PMID- 26834960 TI - Risk of intracranial hypertension with intrauterine levonorgestrel. PMID- 26834958 TI - Spontaneously reported haemorrhagic adverse events associated with rivaroxaban and dabigatran in Australia. AB - OBJECTIVES: The objective of our study was to describe spontaneously reported haemorrhagic adverse events associated with rivaroxaban and dabigatran in Australia. METHODS: Data were sourced from the Australian Therapeutic Goods Administration (TGA) Database of Adverse Event Notifications between June 2009 and May 2014. Records of haemorrhagic adverse events in which rivaroxaban or dabigatran was considered as a potential cause were analysed. RESULTS: There were 240 haemorrhagic adverse events associated with rivaroxaban and 504 associated with dabigatran. Age was specified for 164 (68%) haemorrhages associated with rivaroxaban, of which 101 occurred in people aged ?75 years. Age was specified for 437 (87%) haemorrhages associated with dabigatran, of which 300 occurred in people aged ?75 years. Time from treatment initiation to haemorrhage was specified for 122 (51%) haemorrhages associated with rivaroxaban, with 69 (57%) haemorrhages occurring within 30 days of rivaroxaban initiation. Time from treatment initiation to haemorrhage was specified for 253 (50%) haemorrhages associated with dabigatran, with 123 (49%) haemorrhages occurring within 30 days of dabigatran initiation. Gastrointestinal (GI) haemorrhages were the most frequent type of haemorrhages associated with both rivaroxaban (n = 105, 44%) and dabigatran (n = 302, 60%). Data were available on the severity of haemorrhage for 101 (42%) haemorrhages associated with rivaroxaban, with haemorrhage leading to death in 17 people. The severity of haemorrhage was specified for 384 (76%) haemorrhages associated with dabigatran, with haemorrhage leading to death in 61 people. CONCLUSIONS: Our study highlights the need for research on the haemorrhagic complications of anticoagulation in clinical care. A considerable proportion of reported haemorrhagic events occurred within 30 days of rivaroxaban and dabigatran initiation. This highlights the importance of considering bleeding risk at the time of treatment initiation. PMID- 26834961 TI - Risk of intracranial hypertension with intrauterine levonorgestrel: reply. PMID- 26834959 TI - Predicting risk of adverse drug reactions in older adults. AB - Adverse drug reactions (ADRs) are common in older adults, with falls, orthostatic hypotension, delirium, renal failure, gastrointestinal and intracranial bleeding being amongst the most common clinical manifestations. ADR risk increases with age-related changes in pharmacokinetics and pharmacodynamics, increasing burden of comorbidity, polypharmacy, inappropriate prescribing and suboptimal monitoring of drugs. ADRs are a preventable cause of harm to patients and an unnecessary waste of healthcare resources. Several ADR risk tools exist but none has sufficient predictive value for clinical practice. Good clinical practice for detecting and predicting ADRs in vulnerable patients includes detailed documentation and regular review of prescribed and over-the-counter medications through standardized medication reconciliation. New medications should be prescribed cautiously with clear therapeutic goals and recognition of the impact a drug can have on multiple organ systems. Prescribers should regularly review medication efficacy and be vigilant for ADRs and their contributory risk factors. Deprescribing should occur at an individual level when drugs are no longer efficacious or beneficial or when safer alternatives exist. Inappropriate prescribing and unnecessary polypharmacy should be minimized. Comprehensive geriatric assessment and the use of explicit prescribing criteria can be useful in this regard. PMID- 26834964 TI - Editorial. PMID- 26834962 TI - Exercise-induced mitochondrial p53 repairs mtDNA mutations in mutator mice. AB - BACKGROUND: Human genetic disorders and transgenic mouse models have shown that mitochondrial DNA (mtDNA) mutations and telomere dysfunction instigate the aging process. Epidemiologically, exercise is associated with greater life expectancy and reduced risk of chronic diseases. While the beneficial effects of exercise are well established, the molecular mechanisms instigating these observations remain unclear. RESULTS: Endurance exercise reduces mtDNA mutation burden, alleviates multisystem pathology, and increases lifespan of the mutator mice, with proofreading deficient mitochondrial polymerase gamma (POLG1). We report evidence for a POLG1-independent mtDNA repair pathway mediated by exercise, a surprising notion as POLG1 is canonically considered to be the sole mtDNA repair enzyme. Here, we show that the tumor suppressor protein p53 translocates to mitochondria and facilitates mtDNA mutation repair and mitochondrial biogenesis in response to endurance exercise. Indeed, in mutator mice with muscle-specific deletion of p53, exercise failed to prevent mtDNA mutations, induce mitochondrial biogenesis, preserve mitochondrial morphology, reverse sarcopenia, or mitigate premature mortality. CONCLUSIONS: Our data establish a new role for p53 in exercise-mediated maintenance of the mtDNA genome and present mitochondrially targeted p53 as a novel therapeutic modality for diseases of mitochondrial etiology. PMID- 26834965 TI - A 6-week, double-blind, placebo- and haloperidol-controlled, phase II study of lurasidone in patients with acute schizophrenia. AB - OBJECTIVE: The objective of this study was to evaluate the short-term efficacy and safety of the atypical antipsychotic agent lurasidone in the treatment of schizophrenia. METHODS: In this phase II, randomized, double-blind, placebo controlled study, hospitalized adult patients diagnosed with schizophrenia and experiencing an acute exacerbation of psychotic symptoms were randomly assigned to 6 weeks of fixed-dose lurasidone 20 mg/day (n = 71), lurasidone 40 mg/day (n = 67), lurasidone 80 mg/day (n = 71), haloperidol 10 mg/day (n = 72, included to test for assay sensitivity), or placebo (n = 72). Efficacy was assessed using the brief psychiatric rating scale, positive and negative syndrome scale, and clinical global impression-severity. Safety assessments included incidence of adverse events and clinical laboratory measures. RESULTS: Numerical improvement was observed from baseline to week 6 (last observation carried forward) on all efficacy measures in all treatment groups; however, no statistically significant differences were noted between any lurasidone group and placebo, or between haloperidol and placebo. The most common adverse events in lurasidone-treated patients, with an incidence of at least 10% (dose groups combined) and greater than placebo, were sedation (15.3%), dyspepsia (13.4%), nausea (13.4%), akathisia (12.4%), and vomiting (10.5%); for haloperidol, the most common adverse events (incidence ? 10% and greater than placebo) were extrapyramidal disorder (20.8%), sedation (19.4%), akathisia (19.4%), dystonia (15.3%), insomnia (13.9%), and somnolence (12.5%). Lurasidone was associated with minimal changes in weight, metabolic parameters, and prolactin levels. CONCLUSIONS: None of the lurasidone groups separated from placebo in this clinical study of patients with acute schizophrenia. In addition, haloperidol, which was included for assay sensitivity, did not separate from placebo, resulting in a failed study. Possible reasons for the lack of assay sensitivity in this study include the use of multiple active treatment arms and the relatively large placebo response. Consistent with other studies, lurasidone was generally safe and well tolerated, with minimal effects on weight or metabolic parameters. PMID- 26834966 TI - Serotonergic antidepressants and increased bleeding risk in patients undergoing breast biopsy. AB - OBJECTIVES: Recent investigations have shown that serotonergic antidepressant (SAd) use may increase the risk of peri-operative bleeding events. Our objective was to evaluate the possibility of a similar association in patients undergoing radiologic breast biopsies. METHODS: We used data from 3890 patients undergoing 6300 biopsy procedures between January 2011 and October 2014 in the Breast Clinic of McGill University Health Centre, Montreal, Canada. In this case-control study, cases were patients reported to have abnormal bleeding during their biopsy by board-certified radiologists. A control group of nonbleeders was selected using matching according to age and type of biopsy. The correlation between abnormal bleeding and SAd use was assessed using bivariate and multivariate statistical analyses. RESULTS: There were 97 patients with abnormal bleeding and 137 matched controls; 10 bleeders (cases) were on SAds (7 citalopram, 3 paroxetine) while only 1 nonbleeder (control group) was on a SAd (low-dose sertraline, 25 mg/day). SAds were significantly associated with increased bleeding risk (10.3% versus 0.7%, Fisher's Exact p = 0.001). Moreover, after adjusting for confounding factors (age, type of biopsy, size of biopsy, needle caliber, pathology result and nonsteroidal anti-inflammatory drug use, multivariate logistic regression confirmed that SAds were associated with elevated bleeding risk (16.2, 95% confidence interval 1.87-140.1, p = 0.01). CONCLUSIONS: This is the first study demonstrating increased bleeding events in breast biopsy patients using SAds. Clinicians should be aware that SAds may be associated with peri-operative bleeding risk, even in relatively minor procedures such as breast biopsies. PMID- 26834968 TI - Clozapine-induced myoclonus: a case report and review of the literature. AB - We describe the case of a young man with treatment-resistant schizophrenia, who developed myoclonus during clozapine titration. This subsequently led to a full tonic-clonic seizure. Clozapine treatment can result in a range of seizure-like activity, the most well-known being tonic-clonic seizures. This case highlights the importance of recognizing and treating clozapine-induced myoclonus, as it can herald the onset of a full seizure, even at low serum clozapine levels. We highlight the variety of ways myoclonus can present clinically and suggest treatment options. PMID- 26834963 TI - Imaging in multiple endocrine neoplasia type 1: recent studies show enhanced sensitivities but increased controversies. AB - In multiple endocrine neoplasia type 1 (MEN1) patients, a number of recent studies compare the ability of different, new imaging modalities to existing modalities to localize the important neuroendocrine tumors (NETs) that contribute to their decreased life expectancy (pancreatic NETs [pNETs] and thymic carcinoids). These included the use of 68Ga-DOTATOC-PET/CT, endoscopic ultrasound and MRI. The current paper analyzes these results in light of current guidelines and controversies involved in the treatment/management of MEN1 patients. Particular attention is paid to results in these studies with thymic carcinoids and nonfunctional pNETs/gastrinomas, which recent studies show are particularly important in determining long-term survival. These studies show a number of promising imaging results but also raise a number of controversies, which will need to be addressed both in their use initially and for serial studies in these patients. PMID- 26834967 TI - Nurses' perceptions of medication adherence in schizophrenia: results of the ADHES cross-sectional questionnaire survey. AB - OBJECTIVES: Poor adherence to antipsychotic treatment is a widespread problem within schizophrenia therapy with serious consequences including increased risks of relapse and rehospitalization. Mounting evidence supports the key roles that nurses play in monitoring patient progress and facilitating long-term treatment adherence. The Adherencia Terapeutica en la Esquizofrenia (ADHES) nurses' survey was designed to assess the opinions of nurses on the causes and management of partial/nonadherence to antipsychotic medication. METHODS: A questionnaire-based cross-sectional survey of 4120 nurses from Europe, the Middle East and Africa. Interpretation of results was based on a descriptive comparison of responses. RESULTS: Nurses perceived 54% of patients seen in the preceding month to be partially/nonadherent to treatment. Most nurses (90%) reported some level of experience with administration of long-acting injectable (LAI) antipsychotics, with 24% of nurses administering >10 injections per month. The majority (85%) of nurses surveyed believed that improving adherence would improve patient outcomes. Nearly half (49%) reported that most of their patients depend on a family member or other nonprofessional carer to remind them to take their medication as prescribed. A similar proportion of nurses (43%) reported that most of their patients relied on a professional to remind them to take medication. Most nurses (92%) felt that ensuring continuous medication with LAI antipsychotics would yield long-term benefits for patients, but their opinion was that over a third of patients were unaware of LAI antipsychotic treatments. In a series of forced options, the strategy used most often by respondents (89%) to promote medication adherence was to build trusting relationships with patients while listening to and interpreting their needs and concerns. Respondents also rated this as the most effective strategy that they used (48%). CONCLUSION: Nurses are highly aware of adherence issues faced by their patients; further patient education on treatment options is needed. PMID- 26834969 TI - A review of the management of antidepressant discontinuation symptoms. AB - Strong evidence supports the existence of a discontinuation syndrome following the withdrawal of antidepressant medication, particularly second-generation antidepressants. The syndrome is a common phenomenon and guidance as to best avoid the symptoms is essential for both practitioners and patients. The current study reviewed the available literature on the best methods of discontinuation for antidepressants in order to avoid or prevent the occurrence of any unpleasant side effects associated with antidepressant withdrawal. Accordingly, an electronic search of the PubMed/MedLine database and Google Scholar was conducted to find relevant literature published within the last 10 years. From this, 18 related articles were identified; five clinical studies, one case series, one consensus panel's recommendations and 11 literature reviews. Of the articles reviewed there is a general consensus as to tapering the drug slowly over a period of weeks or months. Also, in those patients who experience severe symptoms the drug should be reinstated and discontinued more gradually. The discontinuation syndrome does not occur as frequently or severely with longer acting agents such as fluoxetine and therefore it is recommended that switching to this drug prior to withdrawal may be advisable. The articles reviewed also emphasize the need for patient education and reassurance throughout the discontinuation process. One in particular adds that cognitive behavioural therapy may be a useful tool in easing the patients' distress. However, this review highlights the lack of controlled data to support the available guidelines. Furthermore, the guidance which is available is somewhat conflicting. Research approaches should address this issue as well as develop appropriate methods of withdrawal for specific drugs. PMID- 26834970 TI - International publication trends and collaboration performance of China in healthcare science and services research. AB - BACKGROUND: In recent years, China's healthcare reforms and related studies have drawn particular global attention. The main objective of this study is to evaluate quantitatively the publication trends and collaboration performance of China in healthcare science and services (HSS) research. METHODS: Scientometric methods and visualization technology were used to survey the growth and development trends of HSS research based on the Web of Science publications during the past 15 years. RESULTS: China's international publications on HSS research increased rapidly compared to those of the global HSS and Chinese scientific studies. Growth trends indicate that collaboration among countries, institutions and authors has also increased. China's leading partners were all developed countries, such as the US, the UK, Australia and Canada, which have contributed to the majority of the joint publications. The academic impact of publications involving partners from European and American countries was relatively higher than those involving partners from Asian countries. Prominent institutions were universities that could be primarily classified into two groups, namely, Mainland China on the one hand and Hong Kong universities and foreign universities on the other. The most prominent actors were elite institutions, such as Peking University, Fudan University, Chinese University of Hong Kong, University of Hong Kong. The papers published by the Chinese Ministry of Health had relatively high academic impact, whereas those published by Mainland China universities alone had a lower academic impact compared to foreign cooperation papers. Issues related to the Chinese healthcare reform, priority diseases (e.g., breast cancer, HIV/AIDS, tuberculosis, etc.), health systems performance, quality of life and measurement tools, aging problems and research methods have been the most popular HSS topics in China in recent years. CONCLUSIONS: Despite the extensive achievement of the Chinese HSS reforms and research, gaps and challenges remain to be addressed, including those related to health insurance and the effects of the evaluation of essential medicine systems, human resources training and allocation in the health sector, government hospitals reforms and health services systems remodeling. These findings could help scholars and decision-makers understand the current status and likely future trends of the Chinese HSS research, and help them select the most appropriate collaboration partners and policies. PMID- 26834971 TI - Ultimate drivers of native biodiversity change in agricultural systems. AB - The ability to address land degradation and biodiversity loss while maintaining the production of plant and animal products is a key global challenge. Biodiversity decline as a result of vegetation clearance, cultivation, grazing, pesticide and herbicide application, and plantation establishment, amongst other factors, has been widely documented in agricultural ecosystems. In this paper we identify six ultimate drivers that underlie these proximate factors and hence determine what native biodiversity occurs in modern agricultural landscapes; (1) historical legacies; (2) environmental change; (3) economy; (4) social values and awareness; (5) technology and knowledge; and (6) policy and regulation. While historical legacies and environmental change affect native biodiversity directly, all six indirectly affect biodiversity by influencing the decisions that land managers make about the way they use their land and water resources. Understanding these drivers is essential in developing strategies for sustaining native biodiversity in agricultural landscapes into the future. PMID- 26834972 TI - Atypical Cornelia de Lange Syndrome: a case report. AB - Cornelia de Lange Syndrome (CdLS) (also called Bushy Syndrome or Amsterdam dwarfism), is a genetic disorder that can lead to several alterations. This disease affects both physical and psychical development. The various abnormalities include facial dysmorphia (arched eyebrows, synophrys, depressed nasal bridge, long philtrum, down-turned angles of the mouth), upper-extremity malformations, hirsutism, cardiac defects, and gastrointestinal alterations. The prevalence of this syndrome is approximately one per 15,000. Ultrasound is not the perfect means to diagnose CdLS, however, many abnormalities can be detected prenatally by scrupulous image observation. We report an atypical CdLS case characterized by increased nuchal translucency in the first trimester, normal kariotype, saddle nose, micrognathia with receding jaw, low set ears, facies senilis, arthrogryposis of the hands, absence of the Aranzio ductus venous, dilatation of gallbladder and bowel, a unique umbilical artery, increased volume of amniotic fluid, and intrauterine growth retardation ending with the interruption of pregnancy. PMID- 25110579 TI - Ten things to get right for marine conservation planning in the Coral Triangle. AB - Systematic conservation planning increasingly underpins the conservation and management of marine and coastal ecosystems worldwide. Amongst other benefits, conservation planning provides transparency in decision-making, efficiency in the use of limited resources, the ability to minimise conflict between diverse objectives, and to guide strategic expansion of local actions to maximise their cumulative impact. The Coral Triangle has long been recognised as a global marine conservation priority, and has been the subject of huge investment in conservation during the last five years through the Coral Triangle Initiative on Coral Reefs, Fisheries and Food Security. Yet conservation planning has had relatively little influence in this region. To explore why this is the case, we identify and discuss 10 challenges that must be resolved if conservation planning is to effectively inform management actions in the Coral Triangle. These are: making conservation planning accessible; integrating with other planning processes; building local capacity for conservation planning; institutionalising conservation planning within governments; integrating plans across governance levels; planning across governance boundaries; planning for multiple tools and objectives; understanding limitations of data; developing better measures of progress and effectiveness; and making a long term commitment. Most important is a conceptual shift from conservation planning undertaken as a project, to planning undertaken as a process, with dedicated financial and human resources committed to long-term engagement. PMID- 26834975 TI - Dynamics of Ebola epidemics in West Africa 2014. AB - This paper investigates the dynamics of Ebola virus transmission in West Africa during 2014. The reproduction numbers for the total period of epidemic and for different consequent time intervals are estimated based on a simple linear model. It contains one major parameter - the average infectious period that defines the dynamics of epidemics. Numerical implementations are carried out on data collected from three countries Guinea, Sierra Leone and Liberia as well as the total data collected worldwide. Predictions are provided by considering different scenarios involving the average times of infectiousness for the next few months and the end of the current epidemic is estimated according to each scenario. PMID- 26629331 TI - The PDB database is a rich source of alpha-helical anti-microbial peptides to combat disease causing pathogens. AB - The therapeutic potential of alpha-helical anti-microbial peptides (AH-AMP) to combat pathogens is fast gaining prominence. Based on recently published open access software for characterizing alpha-helical peptides (PAGAL), we elucidate a search methodology (SCALPEL) that leverages the massive structural data pre existing in the PDB database to obtain AH-AMPs belonging to the host proteome. We provide in vitro validation of SCALPEL on plant pathogens ( Xylella fastidiosa, Xanthomonas arboricola and Liberibacter crescens) by identifying AH-AMPs that mirror the function and properties of cecropin B, a well-studied AH-AMP. The identified peptides include a linear AH-AMP present within the existing structure of phosphoenolpyruvate carboxylase (PPC20), and an AH-AMP mimicing the properties of the two alpha-helices of cecropin B from chitinase (CHITI25). The minimum inhibitory concentration of these peptides are comparable to that of cecropin B, while anionic peptides used as control failed to show any inhibitory effect on these pathogens. Substitute therapies in place of conventional chemotherapies using membrane permeabilizing peptides like these might also prove effective to target cancer cells. The use of native structures from the same organism could possibly ensure that administration of such peptides will be better tolerated and not elicit an adverse immune response. We suggest a similar approach to target Ebola epitopes, enumerated using PAGAL recently, by selecting suitable peptides from the human proteome, especially in wake of recent reports of cationic amphiphiles inhibiting virus entry and infection. PMID- 26834976 TI - Nutrition transition in South Asia: the emergence of non-communicable chronic diseases. AB - OVERVIEW: South Asian countries have experienced a remarkable economic growth during last two decades along with subsequent transformation in social, economic and food systems. Rising disposable income levels continue to drive the nutrition transition characterized by a shift from a traditional high-carbohydrate, low-fat diets towards diets with a lower carbohydrate and higher proportion of saturated fat, sugar and salt. Steered by various transitions in demographic, economic and nutritional terms, South Asian population are experiencing a rapidly changing disease profile. While the healthcare systems have long been striving to disentangle from the vicious cycle of poverty and undernutrition, South Asian countries are now confronted with an emerging epidemic of obesity and a constellation of other non-communicable diseases (NCDs). This dual burden is bringing about a serious health and economic conundrum and is generating enormous pressure on the already overstretched healthcare system of South Asian countries. OBJECTIVES: The Nutrition transition has been a very popular topic in the field of human nutrition during last few decades and many countries and broad geographic regions have been studied. However there is no review on this topic in the context of South Asia as yet. The main purpose of this review is to highlight the factors accounting for the onset of nutrition transition and its subsequent impact on epidemiological transition in five major South Asian countries including Bangladesh, India, Nepal, Pakistan and Sri Lanka. Special emphasis was given on India and Bangladesh as they together account for 94% of the regional population and about half world's malnourished population. METHODS: This study is literature based. Main data sources were published research articles obtained through an electronic medical databases search. PMID- 26834978 TI - Is MTHFD1 polymorphisms rs 2236225 (c.1958G>A) associated with the susceptibility of NSCL/P? A systematic review and meta-analysis. AB - AIMS: To investigate the association between the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) polymorphism rs 2236225 (c.1958G>A) and susceptibility to non-syndromic cleft of the lip and/or palate (NSCL/P). METHODS: An extensive literature review has been conducted using PubMed, Web of Science, Cochrane Library, Google Scholar, the China National Knowledge Infrastructure (CNKI), and Wanfang Database for eligible researches. The terms for searching were "cleft lip OR cleft palate OR CLP OR CL/P OR oral facial cleft OR OFC" AND "methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 OR methenyltetrahydrofolate cyclohydrolase formyltetrahydrofolate synthetase OR MTHFD1 OR MTHFD". Two independent researchers screened, evaluated and extracted the data of included studies. The pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated by random effects model under five gene models. Subgroup, sensitivity analysis and publication bias were also assessed. RESULTS: Ten case-control studies have been included in the systematic review and eight studies have been considered for the meta-analysis. Overall, the MTHFD1 polymorphism rs2236225 and the risk of NSCL/P showed pooled OR (95% CI) of 1.02 (0.86-1.21) under allelic model. A higher degree of heterogeneity was observed in Asian countries (I (2) = 75.6%) compared to non-Asian countries (I (2) = 48.9%). Similar consequence appeared in the subgroup of children (I (2) = 78.6%) compared with that of mothers (I (2) = 0.0%). There was no significant difference in the publication bias by the Begg's funnel plot (P = 0.711) and Egger's regression test (P = 0.746). CONCLUSION: Our assessment suggested there was no significant association between the MTHFD1 polymorphism rs 2236225 (c.1958G>A) and the susceptibility to NSCL/P. Further investigations using a large sample size and a more advanced technique should be adopted to reach a more precise conclusion in the future. PMID- 25977756 TI - I drink for my liver, Doc: emerging evidence that coffee prevents cirrhosis. AB - Evidence demonstrating that regular ingestion of coffee has salutary effects on patients with chronic liver disease is accumulating rapidly. Specifically, it appears that coffee ingestion can slow the progression of liver fibrosis, preventing cirrhosis and hepatocellular carcinoma (HCC). This should excite clinicians and scientists alike, since these observations, if true, would create effective, testable hypotheses that should lead to improved understanding on fibrosis pathogenesis and thus may generate novel pharmacologic treatments of patients with chronic liver disease. This review is designed to examine the relevant clinical and epidemiological data in critical fashion and to examine the putative pharmacological effects of coffee relevant to the pathogenesis of liver fibrosis and cirrhosis. We hope that this will inspire relevant critical analyses, especially among "coffee skeptics". Of note, one major assumption made by this review is that the bulk of the effects of coffee consumption are mediated by caffeine, rather than by other chemical constituents of coffee. Our rationales for this assumption are threefold: first, caffeine's effects on adenosinergic signaling provide testable hypotheses; second, although there are myriad chemical constituents of coffee, they are present in very low concentrations, and perhaps more importantly, vary greatly between coffee products and production methods (it is important to note that we do not dismiss the "botanical" hypothesis here; rather, we do not emphasize it at present due to the limitations of the studies examined); lastly, some (but not all) observational studies have examined both coffee and non-coffee caffeine consumption and found consistent effects, and when examined, no benefit to decaffeinated coffee has been observed. Further, in the interval since we examined this phenomenon last, further evidence has accumulated supporting caffeine as the effector molecule for coffee's salutary effects. PMID- 26834980 TI - PHENOstruct: Prediction of human phenotype ontology terms using heterogeneous data sources. AB - The human phenotype ontology (HPO) was recently developed as a standardized vocabulary for describing the phenotype abnormalities associated with human diseases. At present, only a small fraction of human protein coding genes have HPO annotations. But, researchers believe that a large portion of currently unannotated genes are related to disease phenotypes. Therefore, it is important to predict gene-HPO term associations using accurate computational methods. In this work we demonstrate the performance advantage of the structured SVM approach which was shown to be highly effective for Gene Ontology term prediction in comparison to several baseline methods. Furthermore, we highlight a collection of informative data sources suitable for the problem of predicting gene-HPO associations, including large scale literature mining data. PMID- 26834981 TI - Case Report: A case report of unstable Hangman fracture in a eighty year old male. AB - Herein we discuss a rare variant of hangman's fracture in an eighty year old male presenting without any neurological deficits. We performed X-ray and magnetic resonance imaging (MRI) of the cervical spine to confirm the diagnosis. The patient was placed on a cervical traction which showed good reduction. We performed posterior occipitocervical fusion with bone graft fusion followed by early mobilization. A postoperative scan showed good reduction and purchase of the screws. This case highlights the importance of choosing the correct therapeutic attitude for the management of the geriatric population especially in those who do not have any significant co-morbid conditions. PMID- 26834982 TI - Discovering, Indexing and Interlinking Information Resources. AB - The social media revolution is having a dramatic effect on the world of scientific publication. Scientists now publish their research interests, theories and outcomes across numerous channels, including personal blogs and other thematic web spaces where ideas, activities and partial results are discussed. Accordingly, information systems that facilitate access to scientific literature must learn to cope with this valuable and varied data, evolving to make this research easily discoverable and available to end users. In this paper we describe the incremental process of discovering web resources in the domain of agricultural science and technology. Making use of Linked Open Data methodologies, we interlink a wide array of custom-crawled resources with the AGRIS bibliographic database in order to enrich the user experience of the AGRIS website. We also discuss the SemaGrow Stack, a query federation and data integration infrastructure used to estimate the semantic distance between crawled web resources and AGRIS. PMID- 26834979 TI - Chemotherapy for Late-Stage Cancer Patients: Meta-Analysis of Complete Response Rates. AB - Complete response (CR) rates reported for cytotoxic chemotherapy for late-stage cancer patients are generally low, with few exceptions, regardless of the solid cancer type or drug regimen. We investigated CR rates reported in the literature for clinical trials using chemotherapy alone, across a wide range of tumour types and chemotherapeutic regimens, to determine an overall CR rate for late-stage cancers. A total of 141 reports were located using the PubMed database. A meta analysis was performed of reported CR from 68 chemotherapy trials (total 2732 patients) using standard agents across late-stage solid cancers-a binomial model with random effects was adopted. Mean CR rates were compared for different cancer types, and for chemotherapeutic agents with different mechanisms of action, using a logistic regression. Our results showed that the CR rates for chemotherapy treatment of late-stage cancer were generally low at 7.4%, regardless of the cancer type or drug regimen used. We found no evidence that CR rates differed between different chemotherapy drug types, but amongst different cancer types small CR differences were evident, although none exceeded a mean CR rate of 11%. This remarkable concordance of CR rates regardless of cancer or therapy type remains currently unexplained, and motivates further investigation. PMID- 26834983 TI - Sex-difference affects disease progression in the MRMT-1 model of cancer-induced bone pain. AB - An overwhelming amount of evidence demonstrates sex-induced variation in pain processing, and has thus increased the focus on sex as an essential parameter for optimization of in vivo models in pain research. Mammary cancer cells are often used to model metastatic bone pain in vivo, and are commonly used in both males and females. Here we demonstrate that compared to males, females have an increased capacity for recovery following inoculation of MRMT-1 mammary cells, thus potentially causing a sex-dependent bias of the progression of the pain state. PMID- 26834984 TI - PSFC: a Pathway Signal Flow Calculator App for Cytoscape. AB - Cell signaling pathways are sequences of biochemical reactions that propagate an input signal, such as a hormone binding to a cell-surface receptor, into the cell to trigger a reactive process. Assessment of pathway activities is crucial for determining which pathways play roles in disease versus normal conditions. To date various pathway flow/perturbation assessment tools are available, however they are constrained to specific algorithms and specific data types. There are no accepted standards for evaluation of pathway activities or simulation of flow propagation events in pathways, and the results of different software are difficult to compare. Here we present Pathway Signal Flow Calculator (PSFC), a Cytoscape app for calculation of a pathway signal flow based on the pathway topology and node input data. The app provides a rich framework for customization of different signal flow algorithms to allow users to apply various approaches within a single computational framework. PMID- 26834985 TI - iCTNet2: integrating heterogeneous biological interactions to understand complex traits. AB - iCTNet (integrated Complex Traits Networks) version 2 is a Cytoscape app and database that allows researchers to build heterogeneous networks by integrating a variety of biological interactions, thus offering a systems-level view of human complex traits. iCTNet2 is built from a variety of large-scale biological datasets, collected from public repositories to facilitate the building, visualization and analysis of heterogeneous biological networks in a comprehensive fashion via the Cytoscape platform. iCTNet2 is freely available at the Cytoscape app store. PMID- 26834986 TI - Competition over guarding in the Arabian babbler (Turdoides squamiceps), a cooperative breeder. AB - Observations on 12 groups comprised of two adult males and one adult female (some included one or two fledglings), tame, individually marked, Arabian babblers ( Turdoides squamiceps) in the rift valley in Israel revealed that the babblers compete to guard. The pattern of guarding and the way by which one sentinel replaces another reflect the dominance relationships within the group. The dominant (alpha) male guarded more than any other individual. It interfered with and replaced the guarding by the adult beta male more than it did with the yearlings. About one-third of the replacements occurred less than one minute after the sentinel had assumed guarding. Whereas the dominant often replaced its subordinates directly; subordinates hardly ever replaced their dominants directly. The alpha male often allofed the beta male during the replacement. Replacements and allofeeding of the beta males by the alpha males increased significantly during courtship, when competition over breeding was maximal, and dropped back to their previous level at the start of incubation, highlighting the competitive basis underlying the act of guarding. Competition over altruistic acts, as shown here for guarding, is not compatible with explanations based on the assumption that altruistic acts reduce the fitness (reproductive success) of the altruist. We suggest, in contrast, that by investing in guarding and by intervening in the guarding of its competitors, a babbler demonstrates and signals its quality and its control over its competitors, thereby increasing its prestige and consequently its direct fitness. PMID- 26834987 TI - High Frequency Haplotypes are Expected Events, not Historical Figures. AB - Cultural transmission of reproductive success states that successful men have more children and pass this raised fecundity to their offspring. Balaresque and colleagues found high frequency haplotypes in a Central Asian Y chromosome dataset, which they attribute to cultural transmission of reproductive success by prominent historical men, including Genghis Khan. Using coalescent simulation, we show that these high frequency haplotypes are consistent with a neutral model, where they commonly appear simply by chance. Hence, explanations invoking cultural transmission of reproductive success are statistically unnecessary. PMID- 26834989 TI - Twittering About Research: A Case Study of the World's First Twitter Poster Competition. AB - The Royal Society of Chemistry held, to our knowledge, the world's first Twitter conference at 9am on February 5 (th), 2015. This paper reports the details of the event and discusses the outcomes, such as the potential for the use of social media to enhance scientific communication at conferences. In particular, the present work argues that social media outlets such as Twitter broaden audiences, speed up communication, and force clearer and more concise descriptions of a researcher's work. The benefits of poster presentations are also discussed in terms of potential knowledge exchange and networking. This paper serves as a proof-of-concept approach for improving both the public opinion of the poster, and the enhancement of the poster through an innovative online format that some may feel more comfortable with, compared to face-to-face communication. PMID- 26834988 TI - How to avoid pitfalls in antibody use. AB - Antibody use is ubiquitous in the biomedical sciences. However, determining best research practices has not been trivial. Many commercially available antibodies and antibody-conjugates are poorly characterized and lack proper validation. Uncritical application of such useless tools has contributed to the reproducibility crisis in biomedical research. Despite early initiatives such as MIAPAR or PSI-PAR, a best practice guideline for antibody characterization is still not in prospect. Here, we analyze 24 antibody-related databases and compare their content with regard to validation aspects and coverage. We also provide a flowchart for end-users with all necessary steps to facilitate finding and choosing specific and sensitive antibodies for their experiments. Based on a growing demand for better and standardized validation procedures and characterization guidelines for antibody molecules we have summarized our findings in a five-point plan. We intend to keep the discussion alive and hope that properly used antibodies will remain as central to biomedicine as they are today. PMID- 26834990 TI - The Antibody Two-Step Solution. AB - Problems with antibody quality have been described in numerous recent publications. In the present commentary it is argued that these quality problems are due primarily to issues of antibody variability and antibody validation. Further it is argued that the problem of antibody variability must be solved before validation can be useful. A two-step solution to the antibody problem is thus proposed. PMID- 26834991 TI - The ICR1000 UK exome series: a resource of gene variation in an outbred population. AB - To enhance knowledge of gene variation in outbred populations, and to provide a dataset with utility in research and clinical genomics, we performed exome sequencing of 1,000 UK individuals from the general population and applied a high quality analysis pipeline that includes high sensitivity and specificity for indel detection. Each UK individual has, on average, 21,978 gene variants including 160 rare (0.1%) variants not present in any other individual in the series. These data provide a baseline expectation for gene variation in an outbred population. Summary data of all 295,391 variants we detected are included here and the individual exome sequences are available from the European Genome phenome Archive as the ICR1000 UK exome series. Furthermore, samples and other phenotype and experimental data for these individuals are obtainable through application to the 1958 Birth Cohort committee. PMID- 26834993 TI - From reads to regions: a Bioconductor workflow to detect differential binding in ChIP-seq data. AB - Chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq) is widely used to identify the genomic binding sites for protein of interest. Most conventional approaches to ChIP-seq data analysis involve the detection of the absolute presence (or absence) of a binding site. However, an alternative strategy is to identify changes in the binding intensity between two biological conditions, i.e., differential binding (DB). This may yield more relevant results than conventional analyses, as changes in binding can be associated with the biological difference being investigated. The aim of this article is to facilitate the implementation of DB analyses, by comprehensively describing a computational workflow for the detection of DB regions from ChIP-seq data. The workflow is based primarily on R software packages from the open-source Bioconductor project and covers all steps of the analysis pipeline, from alignment of read sequences to interpretation and visualization of putative DB regions. In particular, detection of DB regions will be conducted using the counts for sliding windows from the csaw package, with statistical modelling performed using methods in the edgeR package. Analyses will be demonstrated on real histone mark and transcription factor data sets. This will provide readers with practical usage examples that can be applied in their own studies. PMID- 26834992 TI - MinION Analysis and Reference Consortium: Phase 1 data release and analysis. AB - The advent of a miniaturized DNA sequencing device with a high-throughput contextual sequencing capability embodies the next generation of large scale sequencing tools. The MinIONTM Access Programme (MAP) was initiated by Oxford Nanopore TechnologiesTM in April 2014, giving public access to their USB-attached miniature sequencing device. The MinION Analysis and Reference Consortium (MARC) was formed by a subset of MAP participants, with the aim of evaluating and providing standard protocols and reference data to the community. Envisaged as a multi-phased project, this study provides the global community with the Phase 1 data from MARC, where the reproducibility of the performance of the MinION was evaluated at multiple sites. Five laboratories on two continents generated data using a control strain of Escherichia coli K-12, preparing and sequencing samples according to a revised ONT protocol. Here, we provide the details of the protocol used, along with a preliminary analysis of the characteristics of typical runs including the consistency, rate, volume and quality of data produced. Further analysis of the Phase 1 data presented here, and additional experiments in Phase 2 of E. coli from MARC are already underway to identify ways to improve and enhance MinION performance. PMID- 26834994 TI - Machine learning models identify molecules active against the Ebola virus in vitro. AB - The search for small molecule inhibitors of Ebola virus (EBOV) has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs) with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC 50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4 aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, alpha7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in vitro. PMID- 26834995 TI - Quality of histone modification antibodies undermines chromatin biology research. AB - Histone post-translational modification (PTM) antibodies are essential research reagents in chromatin biology. However, they suffer from variable properties and insufficient documentation of quality. Antibody manufacturers and vendors should provide detailed lot-specific documentation of quality, rendering further quality checks by end-customers unnecessary. A shift from polyclonal antibodies towards sustainable reagents like monoclonal or recombinant antibodies or histone binding domains would help to improve the reproducibility of experimental work in this field. PMID- 26834996 TI - Feeling the future: A meta-analysis of 90 experiments on the anomalous anticipation of random future events. AB - In 2011, one of the authors (DJB) published a report of nine experiments in the Journal of Personality and Social Psychology purporting to demonstrate that an individual's cognitive and affective responses can be influenced by randomly selected stimulus events that do not occur until after his or her responses have already been made and recorded, a generalized variant of the phenomenon traditionally denoted by the term precognition. To encourage replications, all materials needed to conduct them were made available on request. We here report a meta-analysis of 90 experiments from 33 laboratories in 14 countries which yielded an overall effect greater than 6 sigma, z = 6.40, p = 1.2 * 10 (-10 ) with an effect size (Hedges' g) of 0.09. A Bayesian analysis yielded a Bayes Factor of 1.4 * 10 (9), greatly exceeding the criterion value of 100 for "decisive evidence" in support of the experimental hypothesis. When DJB's original experiments are excluded, the combined effect size for replications by independent investigators is 0.06, z = 4.16, p = 1.1 * 10 (-5), and the BF value is 3,853, again exceeding the criterion for "decisive evidence." The number of potentially unretrieved experiments required to reduce the overall effect size of the complete database to a trivial value of 0.01 is 544, and seven of eight additional statistical tests support the conclusion that the database is not significantly compromised by either selection bias or by " p-hacking"-the selective suppression of findings or analyses that failed to yield statistical significance. P-curve analysis, a recently introduced statistical technique, estimates the true effect size of our database to be 0.20, virtually identical to the effect size of DJB's original experiments (0.22) and the closely related "presentiment" experiments (0.21). We discuss the controversial status of precognition and other anomalous effects collectively known as psi. PMID- 26834998 TI - Fascial Manipulation(r) for chronic aspecific low back pain: a single blinded randomized controlled trial. AB - BACKGROUND: The therapeutic approach to chronic aspecific low back pain (CALBP) has to consider the multifactorial aetiology of the disorder. International guidelines do not agree on unequivocal treatment indications. Recommendations for fascial therapy are few and of low level evidence but several studies indicate strong correlations between fascial thickness and low back pain. This study aims at comparing the effectiveness of Fascial Manipulation(r) associated with a physiotherapy program following guidelines for CALBP compared to a physiotherapy program alone. METHODS: 24 subjects were randomized into two groups, both received eight treatments over 4 weeks. Outcomes were measured at baseline, at the end of therapy and at a 1 month and a 3 months follow-up. Pain was measured with the visual analogue scale (VAS) and the brief pain inventory (BPI), function with the Rolland-Morris disability questionnaire (RMDQ), state of well-being with the short-form 36 health-survey (SF-36). The mean clinical important difference (MCID) was also measured. RESULTS: Patients receiving Fascial Manipulation(r) showed statistically and clinically significant improvements at the end of care for all outcomes, in the short (RMDQ, VAS, BPI) and medium term for VAS and BPI compared to manual therapy. The MCID show significant improvements in the means and percentage of subjects in groups in all outcomes post-treatment, in the short and medium term. CONCLUSION: Fascial tissues were implicated in the aetiology of CALBP and treatment led to decreased symptomatic, improved functional and perceived well-being outcomes that were of greater amplitude compared to manual therapy alone. PMID- 26834997 TI - The dorsal posterior insula is not an island in pain but subserves a fundamental role - Response to: "Evidence against pain specificity in the dorsal posterior insula" by Davis et al. AB - An interesting and valuable discussion has arisen from our recent article (Segerdahl, Mezue et al., 2015) and we are pleased here to have the opportunity to expand on the various points we made. Equally important, we wish to correct several important misunderstandings that were made by Davis and colleagues that possibly contributed to their concerns about power when assessing our paper (e.g. actual subject numbers used in control experiment and the reality of the signal to-noise and sampling of the multi-TI technique we employed). Here, we clarify the methods and analysis plus discuss how we interpret the data in the Brief Communication noting that the extrapolation and inferences made by Davis and colleagues are not consistent with our report or necessarily, in our opinion, what the data supports. We trust this reassures the F1000Research readership regarding the robustness of our results and what we actually concluded in the paper regarding their possible meaning. We are pleased, though, that Davis and colleagues have used our article to raise an important discussion around pain perception, and here offer some further insights towards that broader discussion. PMID- 26834999 TI - Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence. AB - Oral tongue squamous cell carcinomas (OTSCC) are a homogeneous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs) is on the rise; many of whom lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on single nucleotide variations (SNVs), indels, regions with loss of heterozygosity (LOH), and copy number variations (CNVs) from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including human papilloma virus (HPV) infection and tumor recurrence. Apart from the frequent somatic variants harbored in TP53, CASP8, RASA1, NOTCH and CDKN2A genes, significant amplifications and/or deletions were detected in chromosomes 6-9, and 11 in the tumors. Variants in CASP8 and CDKN2A were mutually exclusive. CDKN2A, PIK3CA, RASA1 and DMD variants were exclusively linked to smoking, chewing, HPV infection and tumor stage. We also performed a whole-genome gene expression study that identified matrix metalloproteases to be highly expressed in tumors and linked pathways involving arachidonic acid and NF-k-B to habits and distant metastasis, respectively. Functional knockdown studies in cell lines demonstrated the role of CASP8 in a HPV-negative OTSCC cell line. Finally, we identified a 38-gene minimal signature that predicts tumor recurrence using an ensemble machine-learning method. Taken together, this study links molecular signatures to various clinical and epidemiological factors in a homogeneous tumor population with a relatively high HPV prevalence. PMID- 26835000 TI - HiCUP: pipeline for mapping and processing Hi-C data. AB - HiCUP is a pipeline for processing sequence data generated by Hi-C and Capture Hi C (CHi-C) experiments, which are techniques used to investigate three-dimensional genomic organisation. The pipeline maps data to a specified reference genome and removes artefacts that would otherwise hinder subsequent analysis. HiCUP also produces an easy-to-interpret yet detailed quality control (QC) report that assists in refining experimental protocols for future studies. The software is freely available and has already been used for processing Hi-C and CHi-C data in several recently published peer-reviewed studies. PMID- 26835001 TI - Case Report: Delayed presentation of penile epidermoid cyst following reconstruction for Peyronie's disease. AB - Penile masses are a concerning finding for both patient and clinician upon initial presentation. There is a wide differential for penile masses from the benign (fibrous plaques, cysts, ulcerative lesions, benign penile pearly papules, etc.) to more concerning malignant lesions. A proper history and physical is the first step to determining the etiology of the mass and any future clinical interventions. In this paper, we review a case of a 73-year-old male who is found to have an enlarging mass during work-up for possible placement of inflatable penile prosthesis. Fortunately, the mass was determined to be a benign epidermoid cyst presenting thirty years after reconstruction for Peyronie's disease using dermal penile skin graft. With this unique presentation we review the scant literature on penile mass formation following Peyronie's repair. PMID- 26835002 TI - The representation of research in the national curriculum and secondary school pupils' perceptions of research, its function, usefulness and value to their lives. AB - Young people's views on research, how it's conducted and whether it's important, influences the decisions they make about their further studies and career choices. We investigate how research is represented within the English national curriculum and the examination boards because we recognise that what is being taught influences secondary pupil views on research. We use questionnaire data to focus particularly on pupil perceptions of research in the sciences and the scientific method. The questionnaire was a 25-item Likert Scale (1-5) distributed to seven collaborating schools. We received 2634 returns from pupils across key stages 3, 4 and 5. We also asked teachers to complete the questionnaire to reflect how they thought their pupils would respond. We received 54 teacher responses. Statistically significant differences in the responses were identified through a chi-square test on SPSS and the interpretive part of our analysis considers how the term 'research' appears in the national curriculum for England and Wales and the three main English exam boards. The main theoretical construct that informs our analysis is Angela Brew's 4-tier descriptor of perceptions of research (domino, trading, layer, journey). We use this framework to map the national curriculum for Science in England to establish the when, what and how research is presented to school pupils in England and Wales. We highlight and discuss certain pupil views on: research as involving the identification of a research question; research as a means to confirm one's own opinion; research as involving the generation of new knowledge and the collection of new data, such as interviews and questionnaires as well as laboratory work, field trips and library searches. We also discuss pupils' statements of confidence in their ability to do research, school experiences of research, perceptions of difficulty and importance of research to future career choice. PMID- 26835004 TI - A pocket guide to electronic laboratory notebooks in the academic life sciences. AB - Every professional doing active research in the life sciences is required to keep a laboratory notebook. However, while science has changed dramatically over the last centuries, laboratory notebooks have remained essentially unchanged since pre-modern science. We argue that the implementation of electronic laboratory notebooks (eLN) in academic research is overdue, and we provide researchers and their institutions with the background and practical knowledge to select and initiate the implementation of an eLN in their laboratories. In addition, we present data from surveying biomedical researchers and technicians regarding which hypothetical features and functionalities they hope to see implemented in an eLN, and which ones they regard as less important. We also present data on acceptance and satisfaction of those who have recently switched from paper laboratory notebook to an eLN. We thus provide answers to the following questions: What does an electronic laboratory notebook afford a biomedical researcher, what does it require, and how should one go about implementing it? PMID- 26835003 TI - Pilot experience with opebacan/rBPI 21 in myeloablative hematopoietic cell transplantation. AB - Bacterial infection and inflammation contribute significantly to the morbidity and mortality of myeloablative allogeneic hematopoietic cell transplantation (HCT). Endotoxin, a component of the outer membrane of Gram-negative bacteria, is a potent inflammatory stimulus in humans. Bactericidal/permeability increasing protein (BPI), a constituent of human neutrophil granules, binds endotoxin thereby precluding endotoxin-induced inflammation and also has direct anti infective properties against bacteria. As a consequence of myeloablative therapy used in preparation for hematopoietic cell infusion, patients experience gastrointestinal leak of bacteria and bacterial toxins into the systemic circulation and a period of inflammatory cytokine elevation associated with subsequent regimen-related toxicities. Patients frequently become endotoxemic and febrile as well as BPI-deficient due to sustained neutropenia. To examine whether enhancing endotoxin-neutralizing and anti-infective activity by exogenous administration of a recombinant N-terminal fragment of BPI (rBPI 21, generic name opebacan) might ameliorate regimen-related toxicities including infection, we recruited patients scheduled to undergo myeloablative HCT to participate in a proof-of-concept prospective phase I/II trial. After the HCT preparative regimen was completed, opebacan was initiated 18-36 hours prior to administration of allogeneic hematopoietic stem cells (defined as Day 0) and continued for 72 hours. The trial was to have included escalation of rBPI 21 dose and duration but was stopped prematurely due to lack of further drug availability. Therefore, to better understand the clinical course of opebacan-treated patients (n=6), we compared their outcomes with a comparable cohort meeting the same eligibility criteria and enrolled in a non-interventional myeloablative HCT observational study (n = 35). Opebacan-treated participants had earlier platelet engraftment (p=0.005), mirroring beneficial effects of rBPI 21 previously observed in irradiated mice, fewer documented infections (p=0.03) and appeared less likely to experience significant regimen-related toxicities (p=0.05). This small pilot experience supports the potential utility of rBPI 21 in ameliorating HCT-related morbidity and merits further exploration. PMID- 26835005 TI - The effect of cold water endurance swimming on core temperature in aspiring English Channel swimmers. AB - BACKGROUND: The purpose of this study was to determine if cold water swimmers (CWS) developed hypothermia over a 6-h cold water endurance swim and whether body composition, stroke rate (SR) or personal characteristics correlated with core temperature (TC) change. Nine experienced male and female CWS who were aspiring English Channel (EC) swimmers volunteered to participate. Subjects aimed to complete their 6-h EC qualifying swim (water 15-15.8 degrees C/air 15-25 degrees C) while researchers intermittently monitored TC and SR. Data obtained included anthropometry (height, mass, segmental body composition), training volume and EC completion. RESULTS: Of the nine swimmers who volunteered, all successfully completed their EC qualifying swim. Six CWS had complete data included in analysis. One CWS demonstrated hypothermia (34.8 degrees C) at 6-h. TC rate of decline was slower in the first 3 h (-0.06 degrees C/hr) compared to the last 3 h (-0.36 degrees C/hr) of the swim. Older age was significantly correlated to TC change (r = -0.901, p < 0.05) and SR change (r = -0.915, p < 0.05). Absolute and percentage body fat (BF) were not significantly associated with higher TC. Mean SR over the 6-h swim was 57.8 spm (range 48-73 spm), and a significant (p < 0.05) decline in SR was observed over the 6 h (-9.7 %). A strong, positive correlation was found between SR change between 3 and 6 h and TC over the 6 h (r = 0.840, p < 0.05) and TC from 3-6 h (r = 0.827, p < 0.05). Seven of the nine participants (77.8 %) in this study successfully completed the EC crossing. Successful EC swimmers swam in the pool and open water (OW); however, they swam significantly [t (7) = -2.433, p < 0.05] more kilometres (M = 19.09 km/wk +/- 5.55) in OW than unsuccessful (M = 9 km/wk +/- 1.41) EC swimmers. There was a significant relationship between EC crossing time and height (r = -0.817, p < 0.05), but no other variables and EC crossing time. CONCLUSIONS: Cold water endurance swim (CWES) of 6-h duration at 15-16 degrees C resulted in TC reduction in the majority of swimmers regardless of anthropometry. More research is required to determine why some CWS are able to maintain their TC throughout a CWES. Our results indicate that older swimmers are at greater risk of developing hypothermia, and that SR decline is an indicator of TC decline. Our results also suggest that OW swimming training combined with pool training is important for EC swim success. PMID- 26835006 TI - Exploration of over the counter sales of antibiotics in community pharmacies of Addis Ababa, Ethiopia: pharmacy professionals' perspective. AB - BACKGROUND: Over the counter sale of antibiotics is a global problem and it is increasingly recognized as a source of antibiotic misuse and is believed to increase treatment costs, adverse effects of treatment and emergence of resistance. The increasing trend of over the counter sale of antibiotics in Ethiopia calls for exploration of why such dispensing is practiced. This study aims to explore reasons for over the counter sale of antibiotics in the community pharmacies of Addis Ababa, Ethiopia. METHODS: A phenomenological qualitative study was conducted in five randomly selected community pharmacies of Addis Ababa. One pharmacy professional from each pharmacy were interviewed at the spot using semi-structured, open-ended interview checklist. Besides, observation of professionals' dispensing practice was made for at least one hour in the same community pharmacies using an observation checklist. Findings were categorized into specific themes that were developed following the objectives. This was facilitated by use of OpenCode 3.6 software. RESULTS: All participants pointed out that antibiotics were frequently dispensed without prescription and contend that the trend of such dispensing has been increasing. The findings indicated that the nonprescription sales of antibiotics were common for Amoxicillin, Ciprofloxacin and Cotrimoxazole. The poor, less educated and younger groups of the population were reported to frequently request antibiotics without prescription. The main reasons for nonprescription sale of antibiotics by pharmacy professionals were found to be related to pharmacy owner's influence to maximize revenue, customer's pressure, weak regulatory mechanism and professional conflicts of interest. CONCLUSION: The study shows that nonprescription sale of antibiotics was common practice at least in Addis Ababa. The main reasons for this malpractice were the need to maximize revenue and weak regulatory mechanism. Hence, strong regulatory enforcement and community awareness campaign is called for to limit nonprescription sale of antibiotics. PMID- 26835007 TI - Diluting ferric carboxymaltose in sodium chloride infusion solution (0.9% w/v) in polypropylene bottles and bags: effects on chemical stability. AB - OBJECTIVES: This study was designed to assess the physicochemical stability of colloidal ferric carboxymaltose solution (Ferinject) when diluted and stored in polypropylene (PP) bottles and bags for infusion. METHODS: Two batches of ferric carboxymaltose solution (Ferinject) were diluted (500 mg, 200 mg and 100 mg iron in 100 mL saline) in PP bottles or bags under aseptic conditions. The diluted solutions were stored at 30 degrees C and 75%+/-5% relative humidity (rH) for 72 h, and samples were withdrawn aseptically at preparation and after 24 h, 48 h and 72 h. Multiple parameters were used to test stability-related measures (pH, total iron and iron (II) content, molecular weight range determination, microbial contamination and particles count >=10 MUm). RESULTS: Overall, Ferinject diluted in 0.9% (w/v) NaCl solution and stored in PP bottles and bags was stable within the specifications for the complex and the acceptability limits set for all assays. In both containers, total iron content remained stable, within 10% of the theoretical iron content, and levels of iron (II) remained far below the threshold of acceptability. All preparations were free from sediments, particle numbers were acceptable and there was no microbial contamination. The molecular weight distribution and polydispersity index were also acceptable. CONCLUSIONS: Under the tested experimental conditions, colloidal ferric carboxymaltose solution (Ferinject) diluted in saline in PP infusion bottles or bags demonstrated physical and chemical stability for up to 72 h at 30 degrees C and 75% rH. Because of the lack of additional clinical data, when using ferric carboxymaltose, physicians/pharmacists should refer to the dilution and storing recommendations given in the product's summary of product characteristics. PMID- 26835009 TI - Factors associated to the use of insecticide treated nets and intermittent preventive treatment for malaria control during pregnancy in Cameroon. AB - BACKGROUND: Malaria in pregnancy has been shown to cause both maternal and infant morbidity and mortality especially in sub Saharan Africa. The World Health Organization therefore recommends the use of insecticide treated nets (ITNs), intermittent preventive treatment (IPT) and effective management of clinical malaria. The main aim of this study was to assess the coverage of ITN and IPT among pregnant women and the factors associated with their use in the Buea Health District of Cameroon. METHODS: A cross sectional study was carried out from April to July 2014, in the Buea Health District which included 292 pregnant women attending antenatal care at clinics in the area. A structured questionnaire was use to obtain demographic data of participants and information on IPT and ITN use. RESULTS: The Overall coverage rate of IPT was 88.7 % and 43.8 % for ITN while the overall non usage rate for IPT and ITN was 11.3 % and 17.5 % respectively. Occupation, educational level, trimester and number of ANC were statistically significant to ITN use by bivariate analyses while being a student/ unemployed (OR = 0.25, 95 % CI = 0.07-0.95)) was negatively associated to ITN use by multivariate analysis. For IPTp-SP, occupation of participants, educational level, trimester of pregnancy and number of ANC were statistically significantly by bivariate analyses while attending ANC just once (OR = 0.006, 95 % CI = 0.00 0.04) was negatively associated to IPTp-SP use by multivariate analyses. CONCLUSION: This study identified that the use of IPT was fairly good, while ITN use was still low despite their free distribution. Therefore, frequent antenatal care visits and involvement of participants in a potential income generating venture (Business or earning a salary) will increase IPT and ITN usage. PMID- 26835008 TI - A cost-minimization analysis of first intention laparoscopic compared to open right hemicolectomy for colon cancer. AB - BACKGROUND: The morbidity, mortality and survival following a laparoscopic right hemicolectomy for colon cancer are equivalent to an open operation. However, the cost of a longer operating time and consumables may offset savings from a shorter length of stay (LOS). A cost minimization study was undertaken to compare the relative costs. METHODS: A retrospective cohort study of consecutive elective right hemicolectomies for colon cancer performed over 5 years by two teams. One team performed an open operation (OG), the other intended to perform all operations laparoscopically (LG). Clinical outcomes and relative costs were evaluated. Results expressed as mean +/- SEM. RESULTS: There were 58 patients in the open group and 56 in the first intention laparoscopic group, of which 77% were completed laparoscopically. There was no difference in age, gender or cancer stage. The complications, mortality and 5-year survival were similar. Anaesthetic (LG = 63 +/- 3, OG = 62 +/- 2 min) and surgical times (LG = 144 +/- 8, OG = 143 +/- 5 min) were similar. Consumables cost ?571 more and the total theatre cost was ?643 +/- 256 higher in the laparoscopic group compared with the open group (p = 0.01). The LOS in the laparoscopic group (4.6 +/- 0.5 days) was less than in the open group (8.3 +/- 1 days, p < 0.01) saving ?1960 +/- 636 per patient. Overall, first intention laparoscopic right hemicolectomies saved ?1316 +/- 733 per patient. A probability sensitivity analysis indicated a 62% probability that a laparoscopic right hemicolectomy was cheaper than an open operation. CONCLUSION: Laparoscopic right hemicolectomy is oncologically equivalent but less costly and should be considered the procedure of choice for right-sided colon cancer unless contraindicated. PMID- 26835010 TI - Association between shortage of energy supply and nuclear gene mutations leading to carcinomatous transformation. AB - Anaerobic bacteria use glycolysis, an oxygen-independent metabolic pathway, whereas energy metabolism in the evolved eukaryotic cell is performed via oxidative phosphorylation, with all eukaryotic cell activities depending upon high energy consumption. However, in cancer cells evolving from eukaryotic cells, the energy metabolism switches from oxidative phosphorylation to glycolysis. The shortage of energy supply induces cancer cells to acquire specific characteristics. Base pair renewal is the most energy-consuming process in the cell, and shortage of energy supply may lead to errors in this process; the more prominent the shortage in energy supply, the more errors are likely to occur in base pair renewal, resulting in gene mutations and expression of cancer cell characteristics. Thus, shortage of energy supply is associated with carcinomatous transformation. PMID- 26835011 TI - PIM1 kinase as a promise of targeted therapy in prostate cancer stem cells. AB - Since the last decade, the PIM family serine/threonine kinases have become a focus in cancer research. Numerous clinical data supports that overexpression of PIM1 is associated with tumor formation in various tissues. However, little is known regarding the function of PIM1 in cancer stem cells. In cancer cells, PIM1 has essential roles in the regulation of the cell cycle, cell proliferation, cell survival and multiple drug resistance. In stem cells, PIM1 kinase exhibits a significant function in stem cell proliferation, self-renewal and expansion. Thus, PIM1 shows a great promise in cancer therapy by targeting stem cells. Furthermore, it is imperative to investigate Pim-1 targeting in cancer stem cells by applicable inhibitors for improving future outcomes. The present review investigated the potential of PIM1 as a therapy target in prostate cancer stem cells. PMID- 26835012 TI - Application of pre-participation cardiovascular screening guidelines to novice older runners and endurance athletes. AB - OBJECTIVES: Despite robust growth in participation in marathons and endurance sports among older individuals, guidance regarding pre-participation cardiovascular evaluation of these athletes is lacking. The objective of this study was to assess the utility of currently available pre-participation cardiovascular evaluation guidelines as applied to a cohort of older novice endurance athletes. METHODS: We applied data from 1457 novice runners and endurance athletes aged 35 years and older to two pre-participation screening tools, the American Heart Association/American College of Sports Medicine Pre Participation Questionnaire and the 2001 Working Group recommendations for pre participation screening of masters athletes (2001 Masters). RESULTS: Application of the American Heart Association/American College of Sports Medicine Pre Participation Questionnaire identified 42.1% for which pre-participation cardiovascular evaluation was indicated. Of those who met criteria, 51.5% reported completion of a healthcare evaluation. Application of the 2001 Masters guidelines identified 75.2% who qualified for pre-participation electrocardiogram and 34.0% for pre-participation stress testing. Of those who met 2001 Masters criteria for pre-participation testing, 43.7% and 24.6% underwent recommended electrocardiogram and stress testing, respectively. While there was modest concordance with recommendations for pre-participation evaluations based on both American Heart Association/American College of Sports Medicine Pre-Participation Questionnaire and 2001 Masters, only athlete age was independently associated with completion of a pre-participation healthcare evaluation and only athlete age and athlete's participation in marathons were independently associated with pre participation stress testing. CONCLUSION: Among older novice endurance athletes, application of the American Heart Association/American College of Sports Medicine Pre-Participation Questionnaire and 2001 Masters guidelines identifies a significant percentage of athletes for whom pre-participation evaluation and testing are recommended. Concordance with these guidelines was modest and providers were primarily influenced by athlete age and competitive goals when planning pre-participation testing. Given the rarity of cardiovascular events among older participants in endurance events, the cost-effectiveness of the American Heart Association/American College of Sports Medicine Pre-Participation Questionnaire and 2001 Masters guidelines may be unacceptable for general use. PMID- 26835013 TI - Test-retest reliability of self-reported diabetes diagnosis in the Norwegian Women and Cancer Study: A population-based longitudinal study (n =33,919). AB - OBJECTIVE: Self-reported information from questionnaires is frequently used in epidemiological studies, but few of these studies provide information on the reproducibility of individual items contained in the questionnaire. We studied the test-retest reliability of self-reported diabetes among 33,919 participants in Norwegian Women and Cancer Study. METHODS: The test-retest reliability of self reported type 1 and type 2 diabetes diagnoses was evaluated between three self administered questionnaires (completed in 1991, 1998, and 2005 by Norwegian Women and Cancer participants) by kappa agreement. The time interval between the test retest studies was ~7 and ~14 years. Sensitivity of the kappa agreement for type 1 and type 2 diabetes diagnoses was assessed. Subgroup analysis was performed to assess whether test-retest reliability varies with age, body mass index, physical activity, education, and smoking status. RESULTS: The kappa agreement for both types of self-reported diabetes diagnoses combined was good (?0.65) for all three test-retest studies (1991-1998, 1991-2005, and 1998-2005). The kappa agreement for type 1 diabetes was good (?0.73) in the 1991-2005 and the 1998-2005 test retest studies, and very good (0.83) in the 1991-1998 test-retest study. The kappa agreement for type 2 diabetes was moderate (0.57) in the 1991-2005 test retest study and good (?0.66) in the 1991-1998 and 1998-2005 test-retest studies. The overall kappa agreement in the 1991-1998 test-retest study was stronger than in the 1991-2005 test-retest study and the 1998-2005 test-retest study. There was no clear pattern of inconsistency in the kappa agreements within different strata of age, BMI, physical activity, and smoking. The kappa agreement was strongest among the respondents with 17 or more years of education, while generally it was weaker among the least educated group. CONCLUSION: The test-retest reliability of the diabetes was acceptable and there was no clear pattern of inconsistency in the kappa agreement stratified by age, body mass index, physical activity, and smoking. The study suggests that self-reported diabetes diagnosis from middle aged women enrolled in the Norwegian Women and Cancer Study is reliable. PMID- 26835014 TI - Pharmacogenomically actionable medications in a safety net health care system. AB - OBJECTIVE: Prior to implementing a trial to evaluate the economic costs and clinical outcomes of pharmacogenetic testing in a large safety net health care system, we determined the number of patients taking targeted medications and their clinical care encounter sites. METHODS: Using 1-year electronic medical record data, we evaluated the number of patients who had started one or more of 30 known pharmacogenomically actionable medications and the number of care encounter sites the patients had visited. RESULTS: Results showed 7039 unique patients who started one or more of the target medications within a 12-month period with visits to 73 care sites within the system. CONCLUSION: Findings suggest that the type of large-scale, multi-drug, multi-gene approach to pharmacogenetic testing we are planning is widely relevant, and successful implementation will require wide-scale education of prescribers and other personnel involved in medication dispensing and handling. PMID- 26835015 TI - In vitro pressure manifolding distribution evaluation of ABThera(TM) Active Abdominal Therapy System, V.A.C.((r)) Abdominal Dressing System, and Barker's vacuum packing technique conducted under dynamic conditions. AB - OBJECTIVES: Temporary abdominal closure methods allow for management of open abdomens where immediate primary closure is not possible and/or where repeat abdominal entries are necessary. We assessed pressure mapping and fluid extraction efficiency of three open abdomen dressing systems: ABThera(TM) Active Abdominal Therapy System, V.A.C.((r)) Abdominal Dressing System, and Barker's vacuum packing technique. METHODS: An in vitro test model was designed to simulate physical conditions present in an open abdomen. The model consisted of a rigid rest platform with elevated central region and a flexible outer layer with centrally located incision. Constant -125 mmHg negative pressure was applied according to the type of system, under simulated dynamic conditions, using albumin-based solution with a viscosity of 14 cP. Data were collected by pressure sensors located circumferentially into three concentric zones: Zone 1 (closest to negative pressure source), Zone 2 (immediately outside of manifolding material edge), and Zone 3 (area most distal from negative pressure source). Each value was the result of approximately 100 pressure readings/zone/experiment with a total of three experiments for each system. RESULTS: Pressure distribution of ABThera Therapy was significantly (p < 0.05) superior to Barker's vacuum packing technique in all three evaluated zones. Similarly, V.A.C. Abdominal Dressing System pressure distribution was significantly (p < 0.05) improved compared to Barker's vacuum packing technique in all zones. There were no pressure distribution differences in Zone 1 between ABThera Therapy and V.A.C. Abdominal Dressing System; however, in Zones 2 and 3, ABThera Therapy was significantly (p < 0.05) superior to V.A.C. Abdominal Dressing System. CONCLUSIONS: These data suggest that all approaches to negative pressure therapy for open abdomen treatment are not equal. Additional research should be conducted to elucidate clinical implications of data demonstrated here. PMID- 26835016 TI - Improving medication adherence among kidney transplant recipients: Findings from other industries, patient engagement, and behavioral economics-A scoping review. AB - The immune system is a powerful barrier to successful organ transplantation, but one that has been routinely thwarted through modern pharmacotherapeutics. Despite the benefits of immunosuppressive therapy, medication non-adherence leads to an increased risk of graft rejection, higher hospital utilization and costs, and poor outcomes. We conduct a scoping review following Arksey and O'Malley's five stage framework methodology to identify established or novel interventions that could be applied to kidney transplant recipients to improve medication adherence. As the desired outcome is a behavior (taking a pill), we assess three areas: behavioral-focused interventions in other industries, patient engagement theories, and behavioral economic principles. Search strategies included mining business, social sciences, and medical literature with additional guidance from six consultative interviews. Our review suggests that no intervention stands out as superior or likely to be more effective than any other intervention; yet promising strategies and interventions were identified across all three areas examined. Based on our findings, we believe there are five strategies that transplant centers and other organizations can implement to improve medication adherence: (1) Build a foundation of trust; (2) Employ multiple interventions; (3) Stratify the population; (4) Develop collaborative partnerships; and (5) Embed medication adherence into the organization's culture. The effectiveness of these interventions will need to be investigated further, but we believe they are a step in the right direction for organizations to consider in their efforts to improve medication adherence. PMID- 26835017 TI - Variation in patient-provider communication by patient's race and ethnicity, provider type, and continuity in and site of care: An analysis of data from the Connecticut Health Care Survey. AB - OBJECTIVES: The purpose of this study is to examine the quality of patient reported communication with their health care providers using data from a large, statewide survey of patients. We examine the relationship between patient's race and ethnicity, type of health care provider, site of and continuity in care, and the quality of patient-provider communication. METHODS: We analyze data from the Connecticut Health Care Survey, a representative telephone survey of 4608 Connecticut residents conducted between June 2012 and February 2013. Eight measures of patient-provider communication were analyzed using weighted general linear and logistic regression models. RESULTS: Patients' assessments of the quality of communication with their health care providers were generally positive. Hispanic patients, those who received care in a clinic or hospital setting, and those who did not consistently see the same provider reported significantly poorer communication with their providers. CONCLUSION: Our data suggest that improving patient-provider communication for Hispanic patients may be a critical step in achieving health equity. However, increased access to health care delivered outside of physician offices where there may not be consistency in providers across encounters may pose challenges to effective health communication. PMID- 26835018 TI - Characteristics of patients with diabetes who accept referrals for care management services. AB - INTRODUCTION: Patients with chronic conditions can improve their health through participation in self-care programs. However, awareness of and enrollment in these programs are generally low. OBJECTIVE: We sought to identify factors influencing patients' receptiveness to a referral for programs and services supporting chronic disease management. METHODS: We analyzed data from 541 high risk diabetic patients who completed an assessment between 2010 and 2013 from a computer-based, nurse-led Navigator referral program within a large primary care clinic. We compared patients who accepted a referral to those who declined. RESULTS: A total of 318 patients (75%) accepted 583 referrals, of which 52% were for self-care programs. Patients who accepted a referral had more primary care visits in the previous year, were more likely to be enrolled in another program, expressed more interest in using the phone and family or friends for support, and were more likely to report recent pain than those who declined a referral. DISCUSSION: Understanding what factors influence patients' decisions to consider and participate in self-care programs has important implications for program design and development of strategies to connect patients to programs. This work informs outreach efforts to identify and engage patients who are likely to benefit from self-care activities. PMID- 26835019 TI - Retrospective analysis of the prevalence of and factors associated with condom use among young HIV-infected women in Cameroon. AB - OBJECTIVES: Young women are more likely to be infected with HIV globally, in sub Saharan Africa, and in Cameroon. Despite its clear clinical and public health benefits, condom use among HIV-infected women continues to be low. The objective of this study was to describe the prevalence of inconsistent condom use among HIV infected women in Cameroon and the factors associated with it. METHODS: We conducted a cross-sectional study of HIV-infected young women aged 17-26 years from three semi-urban HIV clinics in the Northwest Region of Cameroon. This study was a subgroup analysis of a previously reported study on inconsistent condom use in HIV-infected and -uninfected youth. Inconsistent condom use was defined as reporting "sometimes" or "never" to questions regarding frequency of condom use. Logistic regression modeling was used to determine factors associated with inconsistent condom use. RESULTS: A total of 84 participants were recruited and submitted completed questionnaires for analysis. Median age was 24 years (interquartile range = 22-25) and the median age at HIV diagnosis was 21 years (interquartile range = 20-23). Fifty percent of the participants reported no prior schooling or only primary school education. Overall, 61/84 (73%) reported inconsistent condom use. After adjusting for potential confounders, education to the secondary school level was protective against inconsistent condom use (odds ratio = 0.19; confidence interval: 0.04-0.95), and having >=2 pregnancies was associated with inconsistent condom use (odds ratio = 7.52; confidence interval: 1.67-34.00). CONCLUSION: There is a high prevalence of inconsistent condom use among young HIV-infected women in Cameroon, which appears to be associated with lower levels of educational attainment and higher parity. Further larger studies assessing the factors associated with poor condom use in this population are warranted and may inform public health policy in resource-limited settings with high HIV prevalence. PMID- 26835021 TI - Arrhythmia & Electrophysiology Review - Do we Need Another Journal? PMID- 26835020 TI - Apolipoprotein E epsilon4 allele and malondialdehyde level are independent risk factors for Alzheimer's disease. AB - BACKGROUND: The epsilon4 allele of Apolipoprotein E is involved in lipid metabolism. Oxidative stress produces an increase in lipid peroxidation that has been implicated in the pathogenic cascade in Alzheimer's disease. This study estimated the effect of the epsilon4 allele, malondialdehyde and lipid levels on the risk for Alzheimer's disease. METHODS: A total of 41 control subjects and 73 patients with Alzheimer's disease were recruited. The Apolipoprotein E genotype was determined by amplification of exon 4 of the Apolipoprotein E by polymerase chain reaction (PCR); malondialdehyde concentration was determined by high pressure liquid chromatography, and serum lipids were measured by routine photometric techniques. RESULTS: Malondialdehyde levels were significantly higher in Alzheimer's disease patients independent of the Apolipoprotein E genotype and epsilon4 allele. The epsilon4 allele increases the risk of Alzheimer's disease by 5.114 times and elevated malondialdehyde levels increase the risk by 9.342. CONCLUSION: The presence of epsilon4 allele and elevated malondialdehyde levels are independent risk factors for Alzheimer's disease. These findings support the hypothesis that lipid peroxidation and epsilon4 allele contribute to the pathogenic cascade in Alzheimer's disease by different pathways. PMID- 26835022 TI - Risk Stratification in Atrial Fibrillation Patients - A Review Focused on Mortality. AB - Atrial fibrillation (AF) is associated with increased mortality that is largely due to the severe co-morbidities of patients with this rhythm disturbance rather than to its electrocardiographic features. Available evidence indicated that ageing, heart failure and stroke are the most important predictors of all-cause mortality. Additional clinical parameters such as smoking, renal impairment, chronic obstructive pulmonary disease may also identify patients at risk. The prevention of thromboembolic events is based on oral anticoagulant therapy, which reduces the severity and mortality of ischaemic strokes but slightly increase the rate of haemorrhagic events. Most of the traditional risk stratifiers commonly used in patients in sinus rhythm such as New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF) and resting heart rate seem to be less effective in AF patients thus leaving to the physician judgment the main responsibility of identifying patients with an increased mortality risk. PMID- 26835023 TI - Anticoagulation in Atrial Fibrillation. AB - Patients with atrial fibrillation (AF) are at increased thromboembolic risk, and they suffer more severe strokes with worse outcomes. Most thromboembolic complications of AF are eminently preventable with oral anticoagulation, and the increasing numbers of AF patients mean antithrombotic therapy is the most crucial management aspect of this common arrhythmia. Despite the proven efficacy of warfarin, a string of limitations have meant that it is underused by physicians and patients alike. This has prompted a search for new anticoagulants that could overcome many of the inconveniences of dose variability and anticoagulant monitoring associated with warfarin, but without sacrificing efficacy in thromboprophylaxis. The arrival of new oral anticoagulants has been complemented by improved risk stratification schemes, which permit clinicians to easily and reliably identify patients requiring anticoagulation and their bleeding risk. These advances in AF treatment will hopefully translate into improved outcomes for patients, especially as our experience with the new agents grows. PMID- 26835024 TI - Risk Stratification and Therapeutic Approach in Brugada Syndrome. AB - Brugada syndrome (BrS) is a clinical entity characterised by an incomplete right bundle branch block associated with an ST segment elevation in the right precordial leads and a risk of ventricular arrhythmia and sudden death in the absence of structural abnormalities. Patients with a personal history of sudden death have an annual arrhythmia risk of recurrence as high as 10 %. Similarly, the presence of syncope is consistently associated with an increased arrhythmic risk. This risk can be estimated at about 1.5 % per year. The risk is lower in asymptomatic patients. Regarding the relatively high rate of complication of Implantable cardioverter defibrillator (ICD) implantation, in most of the cases, asymptomatic patients with a Brugada syndrome revealed during ajmaline challenge do not need to be implanted. The situation is more complex in patients with a spontaneous type 1 aspect since the risk could be estimated to be around 0.8 % per year. For these patients, a careful evaluation of the arrhythmic risk using all the different tools available is mandatory. PMID- 26835025 TI - What Should the Cardiologist know about Lamin Disease? AB - Lamins are intermediate filament proteins able to polymerise and form an organised meshwork underlying the inner nuclear membrane in most differentiated somatic cells. Mutations in the LMNA gene, which encodes the two major lamin A and C isoforms, cause a diverse range of diseases, called laminopathies, including dilated cardiomyopathy, associated with a poor prognosis and high rate of sudden death due to conduction defect and early ventricular arrhythmia. Identification of mutations in LMNA gene in clinical practice is rapidly increasing, as well as comprehensive cardiac and genetic family screening. As a consequence, cardiologists are more and more frequently faced to difficult questions regarding optimal management of patients and relatives, especially timing for prophylactic cardioverter defibrillator. This review focuses on recent data useful for the clinician, as well as therapeutic perspectives both in human and animal models. PMID- 26835027 TI - Targeting Stable Rotors to Treat Atrial Fibrillation. AB - Therapy for atrial fibrillation (AF) remains suboptimal, in large part because its mechanisms are unclear. While pulmonary vein ectopy may trigger AF, it remains uncertain how AF, once triggered, is actually sustained. Recent discoveries show that human AF is maintained by a small number of rotors or focal sources. AF sources are widely distributed in patient-specific locations, often remote from pulmonary veins and in the right atrium and stable for prolonged periods of time. In a multicentre experience, brief targeted ablation at sources (focal impulse and rotor modulation [FIRM]) terminated AF predominantly to sinus rhythm prior to pulmonary vein isolation and eliminated AF on rigorous followup. This review summarises the evidence for stable rotors and focal sources of human AF and their clinical role as ablation targets to eliminate paroxysmal, persistent and long-standing persistent AF. PMID- 26835026 TI - Catheter Ablation of Atrial Fibrillation - Techniques and Technology. AB - For certain patients with atrial fibrillation (AF) catheter ablation is now an important, therapeutic, intervention. It is established that catheter ablation is more effective than antiarrhythmic drug therapy at maintaining middle-aged patients with paroxysmal AF in sinus rhythm. However, the role of catheter ablation in other patient groups is not yet well defined. Particularly in patients with long-standing persistent AF, heart failure and the elderly, the efficacy of catheter ablation remains uncertain. At experienced centers catheter ablation for AF can be performed with reasonable safety and efficacy. However, major complications can occasionally occur. Late recurrence of AF is not uncommon and many patients will require a further procedure to maintain sinus rhythm. Fortunately, there are promising developments in the techniques and technology used for AF ablation that are likely to improve the outcomes of the procedure. PMID- 26835029 TI - Use and Abuse of Internal Cardioverter Defibrillators for Primary Prevention. AB - Sudden cardiac death (SCD) is one of the leading causes of mortality in developed countries. Internal cardioverter defibrillators (ICDs) have been developed to treat potentially life-threatening ventricular arrhythmias. Multiple randomised trials have been completed to assess the efficacy of primary prevention ICDs in selected populations. In response to the randomised, controlled trials guidelines have been established to help guide physicians in choosing appropriate patients who may benefit from primary prevention ICDs. Unfortunately, many patients who currently fall within the guidelines are either not represented in the clinical trials or disregarded. The morbidity associated with ICD implant is also overlooked and the cost-benefit analyses are exaggerated in favour of ICD implant. This review article summarises major clinical trials addressing primary prevention ICDs, and also highlights the evidence supporting the use and abuse of ICDs. PMID- 26835028 TI - Epicardial Ventricular Tachycardia Ablation for Which Patients? AB - With the widespread use of implantable cardioverter-defibrillators, an increasing number of patients present with ventricular tachycardia (VT). Large multicentre studies have shown that ablation of VT successfully reduces recurrent VT and this procedure is being performed by an increasing number of centres. However, for a number of reasons, many patients experience VT recurrence after ablation. One important reason for VT recurrence is the presence of an epicardial substrate involved in the VT circuit which is not affected by endocardial ablation. Epicardial access and ablation is now frequently performed either after failed endocardial VT ablation or as first-line treatment in selected patients. This review will focus on the available evidence for identifying VT of epicardial origin, and discuss in which patients an epicardial approach would be benefitial. PMID- 26835030 TI - Defibrillation Testing During Defibrillator Implantation. AB - Implantable cardioverter defibrillators (ICDs) terminate ventricular tachycardia (VT) and ventricular fibrillation (VF) with high efficacy. ICDs improve mortality in patients after survived sudden cardiac death (SCD) and in patients at high risk of dying suddenly. All trials which show a benefit of ICD therapy, have performed some kind of defibrillation testing in order to prove correct system function, sensing of VF and effective defibrillation. Current devices show a shock efficacy of 80-90 % for singular shocks and devices provide up to seven rescue shocks. The probability that a device does not terminate an episode of VT or VF should therefore be very low. However, it is difficult to abandon defibrillation testing because prospective data is lacking that demonstrate non inferiority, if ICDs are implanted without some kind of test. Two prospective trials are on the way and will be finish by 2013/14: the SIMPLE and NORDIC trial, which will answer the question if defibrillation testing can be abandoned without any effect on the benefit of ICD therapy or if testing may even be harmful. PMID- 26835032 TI - SmartTouchTM - The Emerging Role of Contact Force Technology in Complex Catheter Ablation. AB - Novel technologies have been developed recently to assess contact between the ablation catheter and the underlying tissue in an attempt to improve safe and effective lesion delivery. The most recently developed technology is the SmartTouchTM catheter which is an open irrigated-tip catheter integrated within the CARTO 3 3D mapping system. In this review we consider the role of contact force technology, evaluate the published data and discuss the potential applications of this novel technology. PMID- 26835033 TI - Arrhythmia & Electrophysiology Review - A Promising Start. PMID- 26835031 TI - Relevance of Monitoring Atrial Fibrillation in Clinical Practice. AB - The monitoring of atrial fibrillation (AF) is performed using a variety of tools, ranging from the conventional Holter electrocardiogram to modern implantable loop recording with remote data exchange. The main clinical areas in AF where monitoring is crucial for decision-making are catheter and surgical ablation, as well as anticoagulation to prevent strokes. Identifying the patient cohort at risk - e.g., those with subclinical silent AF - is a challenge. In addition, the interaction of AF with implanted devices - e.g. AF-triggered inadequate shock therapy - should be the object of continuous monitoring. The prevention of inadequate shock delivery in particular is of major clinical importance. PMID- 26835034 TI - Recent Atrial Fibrillation Guidelines - Looking at Both Sides of the Atlantic. AB - The American College of Cardiology (ACC), the American Heart Association (AHA) and the European Society of Cardiology (ESC) reported joint guidelines on atrial fibrillation (AF) in 2001 and a revised version in 2006. In 2010 new guidelines on AF were published by the ESC, and in 2011 by the American College of Cardiology Foundation (ACCF)/AHA/Heart Rhythm Society (HRS) and by the Canadian Cardiac Society (CCS). Focused updates have also appeared more recently. We reviewed these three sets of AF guidelines and compared their rating systems and their recommendations regarding four major AF management aspects (i.e. long-term rate control strategy, long-term rhythm control strategy, oral anticoagulation and AF catheter ablation). Significant differences were found between guidelines in the quality of evidence or level of evidence and on the strength of recommendations. Use of new anticoagulants and of new antiarrhythmic drug therapy is also discussed in the light of recent trial results. Whether multiplication of guidelines and differences in recommendation impact their implementation in clinical practice, remains to be assessed. PMID- 26835035 TI - Body Surface Electrocardiographic Mapping for Non-invasive Identification of Arrhythmic Sources. AB - The authors describe a novel three-dimensional, 252-lead electrocardiography (ECG) and computed tomography (CT)-based non-invasive cardiac imaging and mapping modality. This technique images potentials, electrograms and activation sequences (isochrones) on the epicardial surface of the heart. This tool has been investigated in the normal cardiac electrophysiology and various tachyarrhythmic, conduction and anomalous depo-repolarisation disorders. The clinical application of this system includes a wide range of electrical disorders like atrial arrhythmias (premature atrial beat, atrial tachycardia, atrial fibrillation), ventricular arrhythmias (premature ventricular beat, ventricular tachycardia) and ventricular pre-excitation (Wolff-Parkinson-White syndrome). In addition, the system has been used in exploring abnormalities of the His-Purkinje conduction like the bundle branch block and intraventricular conduction disturbance and thereby useful in electrically treating the associated heart failure (cardiac resynchronisation). It has a potential role in furthering our understanding of abnormalities of ventricular action potential (depolarisation [Brugada syndrome and repolarisation], long QT and early repolarisation syndromes) and in evaluating the impact of drugs on His-Purkinje conduction and cardiac action potential. PMID- 26835036 TI - Wide Complex Tachycardia - Ventricular Tachycardia or Not Ventricular Tachycardia, That Remains the Question. AB - Arriving at the correct diagnosis in cases of wide complex tachycardia remains problematic for many clinicians. In this paper, we review the historical development of criteria used to differentiate among the major diagnostic possibilities and compare the strengths and weaknesses of various differentiating algorithms. PMID- 26835037 TI - Current Evidence and Recommendations for Rate Control in Atrial Fibrillation. AB - Atrial fibrillation (AF) is the most common cardiac arrhythmia encountered in clinical practice, which is associated with substantial risk of stroke and thromboembolism. As an arrhythmia that is particularly common in the elderly, it is an important contributor towards morbidity and mortality. Ventricular rate control has been a preferred and therapeutically convenient treatment strategy for the management of AF. Recent research in the field of rhythm control has led to the advent of newer antiarrhythmic drugs and catheter ablation techniques as newer therapeutic options. Currently available antiarrhythmic drugs still remain limited by their suboptimal efficacy and significant adverse effects. Catheter ablation as a newer modality to achieve sinus rhythm (SR) continues to evolve, but data on long-term outcomes on its efficacy and mortality outcomes are not yet available. Despite these current developments, rate control continues to be the front-line treatment strategy, especially in older and minimally symptomatic patients who might not tolerate the antiarrhythmic drug treatment. This review article discusses the current evidence and recommendations for ventricular rate control in the management of AF. We also highlight the considerations for rhythm control strategy in the management of patients of AF. PMID- 26835038 TI - Mimics of Hypertrophic Cardiomyopathy - Diagnostic Clues to Aid Early Identification of Phenocopies. AB - Hypertrophic cardiomyopathy (HCM) is the most common genetic cause of cardiomyopathy worldwide. Significant advances and widespread availability of genetic testing have improved detection of the sarcomeric mutations that cause HCM, but have also highlighted the significance of inborn errors of metabolism (IEM) or metabolic storage disorders that can mimic HCM ('HCM phenocopies'). These conditions cannot always be reliably differentiated on the basis of imaging alone. Whilst HCM phenocopies are relatively rare, it is crucial to distinguish these conditions at an early stage as their natural history, management and prognosis vary significantly from that of HCM with sarcomeric mutations. This review illustrates the salient features of HCM phenocopies and stresses the need for a high level of suspicion for these conditions in the assessment of cardiac hypertrophy. PMID- 26835039 TI - Outcomes in Women Undergoing Electrophysiological Procedures. AB - The number of invasive electrophysiological procedures is steadily increasing in Western countries, as the age of the population increases and technologies advance. In recent years, gender-related differences in cardiac rhythm disorders have been increasingly appreciated, which can potentially have a great impact on the outcomes of invasive electrophysiological procedures. Among supraventricular arrhythmias, women have a higher incidence of atrioventricular nodal re-entrant tachycardia and a significantly lower incidence of atrioventricular re-entrant tachycardia compared with males, and present to ablation procedures later and after having failed more antiarrhythmic drugs. The results of catheter ablation of atrial fibrillation in women have been reported worse than in men. This finding is possibly due to a later referral of females to ablation procedures, who present older and with a higher incidence of long-standing persistent atrial fibrillation. With regard to cardiac device implantation procedures, a smaller survival benefit from prophylactic implantable cardioverter defibrillator (ICD) implantation has been shown in women, essentially due to gender-specific differences in the clinical course of patients with severe left ventricular dysfunction, with women dying predominantly from non-arrhythmic causes. On the other side, the clinical outcome of cardiac resynchronisation therapy seems to be more favourable in women, who experience a greater degree of reverse left ventricular remodelling and a striking decrease of heart failure events or mortality after biventricular pacing. This review will summarise the available evidence on gender-related differences in outcomes of invasive electrophysiological procedures. PMID- 26835040 TI - Catheter Ablation for Ventricular Arrhythmias. AB - Catheter ablation has emerged as an important and effective treatment option for many recurrent ventricular arrhythmias. The approach to ablation and the risks and outcomes are largely determined by the nature of the severity and type of underlying heart disease. In patients with structural heart disease, catheter ablation can effectively reduce ventricular tachycardia (VT) episodes and implantable cardioverter defibrillator (ICD) shocks. For VT and symptomatic premature ventricular beats that occur in the absence of structural heart disease, catheter ablation is often effective as the sole therapy. Advances in catheter technology, imaging and mapping techniques have improved success rates for ablation. This review discusses current approaches to mapping and ablation for ventricular arrhythmias. PMID- 26835043 TI - Closed Chest Convergent Epicardial-Endocardial Ablation of Non-paroxysmal Atrial Fibrillation - A Case Series and Literature Review. AB - The closed chest convergent procedure is a multidisciplinary approach to atrial fibrillation (AF) treatment. Epicardial posterior left atrial (PLA) ablation is performed by a cardiac surgeon using a transdiaphragmatic endoscope, immediately followed by percutaneous pulmonary vein (PV) isolation performed by a cardiac electrophysiologist. Interim outcomes for the treatment of non-paroxysmal AF (NPAF) were evaluated based on peri-procedural safety and complications, freedom from recurrent AF, and need for cardioversion or repeat catheter ablation at three, six and 12 months post-procedure. A total of 43 patients (86 % NPAF) underwent the convergent procedure. Patients were 84 % male, with mean age 58.6 +/- 8.7 years. Mean AF duration was 45.4 +/- 40.3 months. Pre-procedure left atrium (LA) volumetric data using cardiac magnetic resonance imaging (MRI) or computed tomography (CT) was available for 30 patients (70 %). Average LA volume was 155.5 +/- 48.4 millilitres (ml); two-thirds of patients had a LA volume >130 ml. There was no operative or peri-operative mortality. Sinus rhythm (SR) was recorded at three months in 31 of 39 (79 %) patients, at six months in 24 of 27 (89 %) patients and at 12 months in nine patients. The convergent procedure is a safe and effective option for both PV isolation and PLA substrate ablation in NPAF patients. Long-term follow-up is required and randomised clinical trials warranted. PMID- 26835044 TI - Arrhythmia & Electrophysiology Review - Moving Forward. PMID- 26835042 TI - The Future of Pulmonary Vein Isolation - Single-shot Devices, Remote Navigation or Improving Conventional Radiofrequency Delivery by Contact Monitoring and Lesion Characterisation? AB - Pulmonary vein isolation is the main goal of atrial fibrillation (AF) ablation to date. Lack of isolation is associated with an increased risk of AF recurrences. Precise navigation to specific target sites, catheter stability and appropriate contact force are requisites for effective radiofrequency applications. Conventional manual-guided point-by-point radiofrequency energy delivery shows limitations to reach them, especially when performed by non-experienced electrophysiologists. New technological alternatives are rapidly arising and becoming clinically available to overcome some of the manual-guided radiofrequency delivery shortcomings. Here, we review the most recent clinical data, potential advantages, shortcomings and future directions of the new ablation strategies for pulmonary vein isolation. PMID- 26835041 TI - Remote Navigation for Complex Arrhythmia. AB - Magnetic navigation has been established as an alternative to conventional, manual catheter navigation for invasive electrophysiology interventions about a decade ago. Besides the obvious advantage of radiation protection for the operator who is positioned remotely from the patient, there are additional benefits of steering the tip of a very floppy catheter. This manuscript reviews the published evidence from simple arrhythmias in patients with normal cardiac anatomy to the most complex congenital heart disease. This progress was made possible by the introduction of improved catheters and most importantly irrigated tip electrodes. PMID- 26835046 TI - A Critical Reappraisal of the Current Clinical Indications to Cardiac Resynchronisation Therapy. AB - Cardiac resynchronisation therapy (CRT) is a well-established non-pharmacological treatment option for patients with refractory symptomatic heart failure (HF) already under optimal medical therapy. CRT is founded on the principle that interventricular conduction disturbances and more in particular left bundle branch block (LBBB) are deleterious to cardiac performance, and may contribute to the systolic and diastolic incompetency typical of patients with HF. Although CRT is associated with a not negligible percentage of non-response, all the international guidelines on chronic HF have extended their indications to CRT, also to patients with less symptomatic HF who are already showing signs of systolic dysfunction and interventricular dyssynchrony, without giving any substantial advice to reduce the number of failures of this therapy. This review seeks to point out the potential issues linked to CRT, with the aim of making a reappraisal of the clinical evidences supporting the current indications to CRT, and to figure out which type of research should be warranted in the field for the future to reduce the percentage of non-responders to this therapy. PMID- 26835047 TI - Cardiac Pacing - Is Telemonitoring Now Essential? AB - Modern pacemakers and implantable defibrillators are able to automatically perform tests executed manually during in-office visits; such as measurement of sensing and pacing thresholds. In addition, the devices also record a wealth of diagnostic data that are of clinical relevance. The advent of wireless technology in these devices allows automatic transmission of these data that can be consulted remotely by the physician. There is now solid evidence indicating that remote device follow-up can safely reduce the number of in-office visits, thereby improving convenience for patients and caregivers alike. Remote monitoring with automatic alerts for arrhythmias, heart failure and technical issues, has been shown to dramatically reduce delay to diagnosis of these events compared with standard follow-up; potentially improving patient safety and outcome. For these reasons, remote device management is becoming the standard of care. PMID- 26835045 TI - What About Tachycardia-induced Cardiomyopathy? AB - Long-standing tachycardia is a well-recognised cause of heart failure and left ventricular dysfunction, and has led to the nomenclature, tachycardia-induced cardiomyopathy (TIC). TIC is generally a reversible cardiomyopathy if the causative tachycardia can be treated effectively, either with medications, surgery or catheter ablation. The diagnosis is usually made after demonstrating recovery of left ventricular function with normalisation of heart rate in the absence of other identifiable aetiologies. One hundred years after the first reported case of TIC, our understanding of the pathophysiology of TIC in humans remains limited despite extensive work in animal models of TIC. In this review we will discuss the proposed mechanisms of TIC, the causative tachyarrhythmias and their treatment, outcomes for patients diagnosed with TIC, and future directions for research and clinical care. PMID- 26835048 TI - The Electrocardiogram in Athletes Revisited. AB - Cardiovascular-related sudden death is the leading cause of mortality in athletes during sport. Thus, it is of clinical importance to identify ECG changes that represent normal adaptation in athletes, and differentiate them from truly pathological findings. However, a distinction between adaptive and pathological ECG changes in athletes is not always easy. This article discusses exercise induced ECG changes and the differential diagnosis of conditions that present with similar ECG patterns. PMID- 26835049 TI - Stroke in Atrial Fibrillation - Long-term Follow-up of Cardiovascular Events. AB - The incidence of atrial fibrillation (AF) was around 1.5 per 1000 person-years in Taiwan. Systemic thromboembolism is the most severe complication of AF. Risk stratification and adequate thromboembolism prophylaxis is the cornerstone of treatment in AF patients. The CHA2DS2-VASc score is powerful in selecting "truly low-risk" patients who are not necessary to receive anticoagulation therapies. It is also useful in predicting thromboembolic events and mortality for patients undergoing AF ablation. Recently, more and more biomarkers and imaging parameters were reported to be associated with adverse events in AF patients. How could these biomarkers and imaging tools change the current strategy of stroke prevention in AF deserves further investigations. PMID- 26835051 TI - The European Heart Rhythm Association Practical Guide on the Use of New Oral Anticoagulants in Patients with Non-valvular Atrial Fibrillation - A Brief Summary. AB - New oral anticoagulants (NOACs) are an alternative to vitamin K antagonists (VKAs) in the prevention of stroke in patients with non-valvular atrial fibrillation (AF). The European Heart Rhythm Association (EHRA) has produced a practical guide to detail the use of NOACs in clinical practice. The guide includes a practical start-up and follow-up scheme, emphasising the importance of strict adherence to the regimen - the anticoagulant effect drops rapidly after 12 24 hours. There is also guidance on how to measure the anticoagulant effect of NOACs, switching between anticoagulant regimes and dealing with dosing errors. Physicians will have to consider the pharmacokinetic effect of drugs and co morbidities when prescribing NOACs - plasma levels of NOACs may be affected by P glycoprotein (P-gp) substrates, as well as cytochrome P450 (CYP3A4) inducers or inhibitors. In patients with chronic kidney disease, reduced doses of NOACs may be indicated. Guidance is also given on the management of bleeding complications, and the cessation and reinitiation of NOACs in patients undergoing surgical interventions. Finally, the use of NOACs in specific clinical situations is considered; these include patients with AF and coronary artery disease (CAD), patients presenting with acute stroke while taking NOACs and patients with cancer. PMID- 26835052 TI - The Role of Three-dimensional Rotational Angiography in Atrial Fibrillation Ablation. AB - Three-dimensional (3D) imaging became the cornerstone of catheter guidance in atrial fibrillation (AF) ablation procedures during the last few years. Multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) have been the technologies of choice for pre-procedural imaging of the left atrium (LA) and the pulmonary veins to make lesions more precisely set in a highly variable and difficult to understand 3D environment. These technologies have been used not only for pre-procedural orientation but have also been overlayed to fluoroscopic views in many fluoroscopy-guided ablation procedures. As image integration into non-fluoroscopic 3D imaging systems became available, 3D reconstructions of MSCT and MRI became the standard approach in many centres. However, 3D imaging is not a cornerstone during ablation as it is not indispensable and ablation can be performed without. Although rare, some very important and key centres do not routinely use 3D imaging during ablation. Being remote to the ablation procedure, these imaging technologies may have the disadvantage of not reflecting the current status of a variable LA volume and scheduling of an additional diagnostic procedure may complicate the workflow of AF ablation procedures. Intra- procedural imaging techniques are likely to overcome both issues. Beside others, rotational angiography has been introduced for proving highly actual imaging by intra-procedural acquisition of 3D shells suitable for overlay to fluoroscopy without need for registration and image integration into 3D mapping systems registered by point-by-point electroanatomical mapping or 3D echocardiographic imaging. PMID- 26835050 TI - Natriuretic Peptides as Predictors of Atrial Fibrillation Recurrences Following Electrical Cardioversion. AB - Electrical cardioversion (ECV) can be effective in restoring sinus rhythm (SR) in the majority of patients with atrial fibrillation (AF). Several factors that predispose to AF recurrences, such as age, AF duration and left atrial size have been used to guide a decision for cardioversion, but increasing evidence suggests that they may be rather poor markers of left atrial structural remodeling that determines the long-term success of a rhythm control strategy. In this context, the use of easily obtainable biomarkers, such as the levels of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), to predict AF recurrences may be preferable. Since ANP production is associated with the extent of functional atrial myocardium, and both ANP and BNP reflect atrial pressure and mechanical stretching, these peptides are good candidate biomarkers to assess predisposition to AF recurrences. In this review we focus on the pathophysiological mechanisms and the available clinical evidence regarding the prediction of AF recurrences following successful ECV from pre-procedural ANP and BNP levels. PMID- 26835053 TI - Role of Magnetic Resonance Imaging of Atrial Fibrosis in Atrial Fibrillation Ablation. AB - Atrial fibrillation (AF) likely involves a complex interplay between triggering activity, usually from pulmonary vein foci, and maintenance of the arrhythmia by an arrhythmogenic substrate. Both components of AF, triggers and substrate have been linked to atrial fibrosis and attendant changes in atrial electrophysiology. Recently, there has been a growing use of imaging modalities, particularly cardiac magnetic resonance (CMR), to quantify the burden of atrial fibrosis and scar in patients either undergoing AF ablation, or who have recently had the procedure. How to use the CMR derived data is still an open area of investigation. The aim of this article is to summarise what is known as atrial fibrosis, as assessed by traditional catheter-based techniques and newer imaging approaches, and to report on novel efforts from our group to advance the use of CMR in AF ablation patients. PMID- 26835054 TI - Imaging-guided Ventricular Tachycardia Ablation. AB - Over the past decades important advances have been made in the field of ventricular tachycardia (VT) ablation, and as a result, VT ablation is now more widely being performed. The identification of ablation target sites still relies on electroanatomical substrate mapping, which is time-consuming, hampered by the intramural location of some scars and limited by epicardial fat. The potential of various imaging modalities to overcome these limitations have stimulated clinical electrophysiologists to perform studies on image integration during VT ablation. Imaging guidance has been used to identify, delineate and characterise the substrate for VT; to provide detailed anatomical information; to avoid ablation on coronary arteries; to delineate epicardial fat tissue; and to assess ablation lesions. In this review, reported applications and the potential advantages and limitations of different imaging modalities are discussed. PMID- 26835055 TI - Observations and Considerations on Patient X-ray Exposure in the Electrophysiology Lab. AB - To assess patient radiation during catheter ablation procedures and operator differences. From 84 patients (51 males, age 63 +/- 10 years) undergoing complex catheter ablation by three experienced operators we collected: body mass index (BMI), procedure type and time, fluoroscopy time, dose area product (DAP), air kerma and X-ray system setting (cine, collimation and angiographic imaging angle). A new factor, fluoroscopy DAP-fluoroscopy time ratio, was introduced to compare operator differences. The results show the average procedure time was 179 (+/- 57) minutes (min), fluoroscopy time was 31 (+/- 21) min, DAP was 26.4 (+/- 19.6) Gy.cm(2) and air kerma was 0.26 (+/- 0.19) Gy. Procedure types were: pulmonary vein isolation (PVI) (52 %), redo PVI (11 %), pulmonary vein ablation catheter (PVAC) (14 %), ventricular tachycardia (VT) (8 %) and others (15 %). Inter-operator difference was observed in fluoroscopy and cine usage. Fluoroscopy DAP-time ratios showed a similar level of patient radiation dose rate by operator A and B (correlation: 0.89), and a significantly higher dose rate by operator C (correlation: 0.20, p<0.001; 0.26, p<0.01, to operator A and B). In conclusion, operators should be aware of patient radiation exposure levels and the influencing factors. Inter- and intra-operator differences can be measured and bench marked for improvement in X-ray efficiency and patient radiation reduction. PMID- 26835056 TI - The Convergent Procedure - A Standardised and Anatomic Approach Addresses the Clinical and Economic Unmet Needs of the Persistent Atrial Fibrillation Population. AB - A standardised treatment management approach is needed to address the escalating worldwide prevalence of atrial fibrillation (AF). The persistent and longstanding persistent AF patient population particularly needs this standardised treatment option to manage their AF. These patients have underlying structural heart disease that result in increased hospitalizations, long-term medical management that increases the cost burden of the healthcare system. Approximately 100 patients have undergone the Convergent Procedure at our center since its introduction 2 years ago, as a treatment option for AF patients. The epicardial and endocardial ablation procedures performed sequentially in a single setting has shown a single procedure success rate of 80%, similar to published success rates at other centers. The epicardial posterior wall isolation silences a majority of known substrates and the endocardial procedure completes the pulmonary vein isolation, creates the cavotricuspid line and provides diagnostic confirmation. The Convergent Procedure should be considered as a first line treatment option for the persistent and longstanding persistent AF patient population who have very limited or no treatment options for the long-term successful management of their AF. PMID- 26835057 TI - Arrhythmia & Electrophysiology Review - Great Expectations. PMID- 26835058 TI - Current Evidence and Recommendations for Cardiac Resynchronisation Therapy. AB - The number of people in Europe living with symptomatic heart failure is increasing. Since its advent in the 1990s, cardiac resynchronisation therapy (CRT) has proven beneficial in terms of morbidity and mortality in selected heart failure (HF) patient populations, when combined with optimal pharmacological therapy. We review the evidence for CRT and the populations of HF patients it is currently shown to benefit, and those in which more research needs to be performed. PMID- 26835059 TI - Endurance Sport Activity and Risk of Atrial Fibrillation - Epidemiology, Proposed Mechanisms and Management. AB - There is evidence for a higher prevalence of atrial fibrillation (AF) in athletes engaged in long-term endurance sports training compared with the general population. Although atrial anatomic adaptations, alterations in autonomic nervous system, chronic systemic inflammation and fibrosis have been proposed as potential mechanisms, they remain speculative. Medical therapy with long-term antiarrhythmic agents or 'pill in the pocket' medications is hampered by limitations, such as sports eligibility and interference with exercise tolerance. AF ablation represents a valid therapeutic option with results similar to these achieved in other patients. Nevertheless, further clinical trials are needed to confirm whether endurance sport practice affects the maintenance of sinus rhythm following catheter ablation of AF. PMID- 26835060 TI - Use of Cardiac Resynchronisation Therapy - Change of Clinical Settings. AB - Current guidelines recommend cardiac resynchronisation therapy (CRT) for patients with severe left ventricular dysfunction (left ventricular ejection fraction [LVEF] <=35 %), QRS duration of >=120-150 ms (Class IA and IB indications) on surface electrocardiogram (ECG) and New York Heart Association (NYHA) class III or IV heart failure (HF) symptoms. Ongoing studies aim to expand the use of CRT in patients with asymptomatic or minimal symptoms left ventricular dysfunction. There have been studies that have shown benefit of CRT extended to this group of patients. There have also been different implications of the role of CRT in patients with atrial fibrillation (AF), patients with narrow QRS duration or with right bundle branch block (RBBB) on surface ECG, as well as patients with end stage renal failure on dialysis therapy. This article aims to review the current body of evidence of expanding use of CRT in these populations. PMID- 26835061 TI - Left Atrial Appendage Closure Devices For Stroke Prevention. AB - Cardioembolic stroke is a major cause of morbidity and mortality in patients with atrial fibrillation (AF). The left atrial appendage (LAA) is the prominent source of clot formation. While systemic anticoagulation is the current standard of care, anticoagulants carry many contraindications and possible complications. Techniques for elimination of the LAA are in various stages of development and early clinical use. In the coming years, accumulating data will help guide the management of AF patients at risk of bleeding as well as potentially become first line therapy to reduce the risk of thromboembolic stroke. The purpose of this article is to review current endovascular and epicardial catheter-based LAA occlusion devices and the clinical data supporting their use. PMID- 26835063 TI - Ablation of Arrhythmias in Patients with Adult Congenital Heart Disease. AB - Arrhythmias in adults with congenital heart disease, most commonly related to previous surgical procedures, are a frequent comorbidity in this growing population thanks to the improved outcome of surgical techniques. Re-entrant circuits around areas of scarring and natural barriers, combined with abnormal haemodynamics and the underlying anatomy, are the most common cause for these arrhythmias. They are often poorly tolerated and medical treatment is frequently inadequate. In recent years, catheter ablation has emerged as a successful therapeutic option. New advanced techniques such as the use of modern three dimensional (3D) navigation systems have contributed to better understanding of the arrhythmia mechanisms and higher success rates of the ablation procedures. In this article we briefly summarise the characteristics of the most common arrhythmias in this patient population and some key aspects in their treatment by catheter ablation. PMID- 26835062 TI - Device-Based Approaches to Modulate the Autonomic Nervous System and Cardiac Electrophysiology. AB - Alterations in resting autonomic tone can be pathogenic in many cardiovascular disease states, such as heart failure and hypertension. Indeed, autonomic modulation by way of beta-blockade is a standard treatment of these conditions. There is a significant interest in developing non-pharmacological methods of autonomic modulation as well. For instance, clinical trials of vagal stimulation and spinal cord stimulation in the treatment of heart failure are currently underway, and renal denervation has been studied recently in the treatment of resistant hypertension. Notably, autonomic stimulation is also a potent modulator of cardiac electrophysiology. Manipulating the autonomic nervous system in studies designed to treat heart failure and hypertension have revealed that autonomic modulation may have a role in the treatment of common atrial and ventricular arrhythmias as well. Experimental data on vagal nerve and spinal cord stimulation suggest that each technique may reduce ventricular arrhythmias. Similarly, renal denervation may play a role in the treatment of atrial fibrillation, as well as in controlling refractory ventricular arrhythmias. In this review, we present the current experimental and clinical data on the effect of these therapeutic modalities on cardiac electrophysiology and their potential role in arrhythmia management. PMID- 26835064 TI - The Potential Role of Edoxaban in Stroke Prevention Guidelines. AB - With the emergence of edoxaban, the oral factor Xa inhibitors now appear consolidated as the dominant class of novel oral anticoagulants (NOACs) for stroke prevention in non-valvular atrial fibrillation (AF). The oral factor Xa inhibitors do not require an adequate time in therapeutic range to be effective, presenting a potential advantage over the vitamin K antagonists (VKAs). Guidelines are changing to reflect the increased choice of anticoagulants and as clinicians move away from the VKAs towards the relative safety and efficacy of NOACs, they must consider which one offers the best therapy for their patient. The ENGAGE-AF study was the latest phase III trial to report on the safety and efficacy of a new factor Xa inhibitor relative to warfarin. Both edoxaban 60mg once daily, and edoxaban 30mg once daily were found to be non-inferior compared to warfarin for the prevention of ischaemic stroke and systemic embolism, being associated with significantly lower rates of major bleeding, intracranial haemorrhage and cardiovascular death. A two-tiered dosing option may present clinicians with a further element of choice for the individual patient. PMID- 26835065 TI - THERMOCOOL(r) SMARTTOUCH(r) CATHETER - The Evidence So Far for Contact Force Technology and the Role of VISITAGTM MODULE. AB - Catheter ablation has become an important modality in the treatment of most cardiac arrhythmias. In recent years there has been significant development of new ablation energies and technologies in an attempt to improve clinical outcomes and decrease disease burden. Ablation failure is often associated with inadequate lesion formation, and catheter-to-myocardial contact force (CF) and catheter stability are two of the parameters required to produce effective lesions during radiofrequency energy application. Recently, CF sensing catheters and tagging modules have been developed to give operators realtime data on catheter force and stability. This review describes the novel THERMOCOOL((r)) SMARTTOUCH((r)) CATHETER (Biosense Webster Inc., CA, US) and VISITAGTM MODULE (Biosense Webster Inc., CA, US) software, and discusses the results of several studies on CF and catheter stability during mapping and ablation of the left atrium and ventricle from our electrophysiology laboratory. We assess the short- and longer-term outcomes during mapping and ablation with and without CF data, as well as the use of the VISITAG MODULETM software, which allows the evaluation of multiple parameters of lesion formation, then integrates and displays this as automatic tags in a relatively objective way. PMID- 26835066 TI - The Role of Continuous Monitoring in Atrial Fibrillation Management. AB - Atrial fibrillation (AF) is the most common cardiac arrhythmia and is strongly associated with stroke risk and a variety of cardiovascular conditions. AF early detection is of paramount importance, in order to define proper medical treatment. This can be challenging due to the often silent and intermittent nature of the rhythm disturbance. Long-term external ECG monitoring may be very helpful, but if less than fully continuous and of long duration it will be not reliable. For this reason continuous monitoring is of increased importance, and outcome measurements of AF treatment trials will be based on the AF burden detected by insertable cardiac monitors (ICM) or therapeutic devices such as pacemakers or ICDs, leading to the paradigm that the detection of AF in the presence of thromboembolic risk factors should be performed wherever possible in order to improve patients' chances. PMID- 26835067 TI - The Promise of Leadless Pacing: Based on Presentations at Nanostim Sponsored Symposium Held at the European Society of Cardiology Congress 2013, Amsterdam, The Netherlands, 2 September 2013. AB - Pacemaker technologies have advanced dramatically over the decades since they were first introduced, and every year many thousands of new implants are performed worldwide. However, there continues to be a high incidence of acute and chronic complications, most of which are linked to the lead or the surgical pocket created to hold the device. A leadless pacemaker offers the possibility of bypassing these complications, but requires a catheter-based delivery system and a means of retrieval at the end of the device's life, as well as a way of repositioning to achieve satisfactory pacing thresholds and R waves, a communication system and low peak energy requirements. A completely self contained leadless pacemaker has recently been developed, and its key characteristics are discussed, along with the results of an efficacy and safety trial in an animal model. The results of the LEADLESS study, the first human trial to look at safety and feasibility of the leadless device, are discussed and the possible implications for future clinical practice examined. PMID- 26835068 TI - Arrhythmia & Electrophysiology Review - Onwards and Upwards. PMID- 26835070 TI - Short QT Syndrome - Review of Diagnosis and Treatment. AB - Short QT syndrome (SQTS) is an inherited cardiac channelopathy characterised by an abnormally short QT interval and increased risk for atrial and ventricular arrhythmias. Diagnosis is based on the evaluation of symptoms (syncope or cardiac arrest), family history and electrocardiogram (ECG) findings. Mutations of cardiac ion channels responsible for the repolarisation orchestrate electrical heterogeneity during the action potential and provide substrate for triggering and maintaining of tachyarrhythmias. Due to the malignant natural history of SQTS, implantable cardioverter defibrillator (ICD) is the first-line therapy in affected patients. This review summarises current data and addresses the genetic basis and clinical features of SQTS. PMID- 26835071 TI - Inherited Arrhythmias - Where do we Stand? AB - This review discusses inherited arrhythmias and conduction disturbances due to genetic disorders. Known channel mutations that are responsible for these conditions are presented, the indications and value of genetic testing are discussed, and a glossary of terms related to the discipline of genetic cardiology has been compiled. PMID- 26835069 TI - Genetic Discoveries in Atrial Fibrillation and Implications for Clinical Practice. AB - Atrial fibrillation (AF) is an arrhythmia with a genetic basis. Over the past decade, rapid advances in genotyping technology have revolutionised research regarding the genetic basis of AF. While AF genetics research was previously largely restricted to familial forms of AF, recent studies have begun to characterise the genetic architecture underlying the form of AF encountered in everyday clinical practice. These discoveries could have a significant impact on the management of AF. However, much work remains before genetic findings can be translated to clinical practice. This review summarises results of studies in AF genetics to date and discusses the potential implications of these findings in clinical practice. PMID- 26835072 TI - Dental Procedures in Patients with Atrial Fibrillation and New Oral Anticoagulants. AB - This review discusses the basic pharmacology of new oral anticoagulants that are used for prevention of thromboembolism in patients with atrial fibrillation. It presents available evidence, and provides recommendations for the management of patients requiring invasive procedures in dental practice. PMID- 26835074 TI - Limited Ablation for Persistent Atrial Fibrillation Using Preprocedure Reverse Remodelling. AB - Pulmonary vein isolation (PVI) has been demonstrated to be a highly effective treatment option for patients with paroxysmal atrial fibrillation (AF), but less effective for patients with persistent AF. The lower efficacy of PVI alone has been attributed to adverse atrial electrical and structural remodelling in the setting of AF. Strategies to improve efficacy of catheter ablation for persistent AF alter these pathophysiological characteristics of atrial tissue remodelling. Here we will review the physiology of atrial electrical remodelling observed during AF and evidence that it is reversible. Further, we will explore its uses to reduce the amount of atrial tissue that needs to be ablated to successfully treat patients with persistent AF. PMID- 26835073 TI - Mechanisms of Atrial Fibrillation - Reentry, Rotors and Reality. AB - Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical practice, yet our understanding of the mechanisms that initiate and sustain this arrhythmia remains quite poor. Over the last 50 years, various mechanisms of AF have been proposed, yet none has been consistently observed in both experimental studies and in humans. Recently, there has been increasing interest in understanding how spiral waves or rotors - which are specific, organised forms of functional reentry - sustain human AF and how they might be therapeutic targets for catheter-based ablation. The following review describes the historical understanding of reentry and AF mechanisms from earlier in the 20th century, advances in our understanding of mechanisms that are able to sustain AF with a focus on rotors and complex fractionated atrial electrograms (CFAEs), and how the study of AF mechanisms has resulted in new strategies for treating AF with novel forms of catheter ablation. PMID- 26835075 TI - New Ablation Technologies and Techniques. AB - Catheter ablation is an established treatment strategy for a range of different cardiac arrhythmias. Over the past decade two major areas of expansion have been ablation of atrial fibrillation (AF) and ventricular tachycardia (VT) in the context of structurally abnormal hearts. In parallel with the expanding role of catheter ablation for AF and VT, multiple novel technologies have been developed which aim to increase safety and procedural success. Areas of development include novel catheter designs, novel navigation technologies and higher resolution imaging techniques. The aim of the present review is to provide an overview of novel developments in AF ablation and VT ablation in patients with of structural cardiac diseases. PMID- 26835077 TI - Cardiac or Other Implantable Electronic Devices and Sleep-disordered Breathing - Implications for Diagnosis and Therapy. AB - Sleep-disordered breathing (SDB) is of growing interest in cardiology because SDB is a highly prevalent comorbidity in patients with a variety of cardiovascular diseases. The prevalence of SDB is particularly high in patients with cardiac dysrhythmias and/or heart failure. In this setting, many patients now have implantable cardiac devices, such as pacemakers, implantable cardioverter defibrillators or implanted cardiac resynchronisation therapy devices (CRT). Treatment of SDB using implantable cardiac devices has been studied previously, with atrial pacing and CRT being shown not to bring about satisfactory results in SDB care. The latest generations of these devices have the capacity to determine transthoracic impedance, to detect and quantify breathing efforts and to identify SDB. The capability of implantable cardiac devices to detect SDB is of potential importance for patients with cardiovascular disease, allowing screening for SDB, monitoring of the course of SDB in relation to cardiac status, and documenting of the effects of treatment. PMID- 26835078 TI - Can we Modulate the Autonomic Nervous System to Improve the Life of Patients with Heart Failure? The Case of Vagal Stimulation. AB - An imbalance of the autonomic nervous system, with reduced vagal and increased sympathetic activity, contributes to pathogenesis and clinical deterioration in heart failure (HF). Experimental studies have demonstrated that vagal stimulation (VS) has an antifibrillatory effect that has proved beneficial in animal models of HF. The potential value of chronic VS in man was first investigated with an implantable neuro-stimulator capable of delivering low current pulses with adjustable parameters to stimulate the right vagus. The results of a pilot study and a small multicentre clinical trial of VS in HF patients appeared to show a favourable clinical effect, and feasibility and safety data were encouraging. An ongoing pivotal clinical trial will provide a definitive assessment of the efficacy and usefulness of chronic VS in HF patients.This approach represents a new and exciting possibility for the management of HF that will provide clinicians with a novel tool to modulate non-pharmacologically the autonomic nervous system in patients with moderate-to-advanced HF. PMID- 26835076 TI - Cardiac Autonomic Denervation for Ablation of Atrial Fibrillation. AB - The influence of the autonomic nervous system (ANS) on triggering and perpetuation of atrial fibrillation (AF) is well established. Ganglionated plexi (GP) ablation achieves autonomic denervation by affecting both the parasympathetic and sympathetic components of the ANS. GP ablation can be accomplished endocardially or epicardially, i.e. during the maze procedure or thoracoscopic approaches. Recent evidence indicates that anatomic GP ablation at relevant atrial sites appears to be safe and improves the results of pulmonary vein isolation in patients with paroxysmal and persistent AF. PMID- 26835080 TI - Arrhythmia & Electrophysiology Review - Time to Reflect. PMID- 26835079 TI - Remote Monitoring for Follow-up of Patients with Cardiac Implantable Electronic Devices. AB - Follow-up of patients with cardiac implantable electronic devices is challenging due to the increasing number and technical complexity of devices coupled to increasing clinical complexity of patients. Remote monitoring (RM) offers the opportunity to optimise clinic workflow and to improve device monitoring and patient management. Several randomised clinical trials and registries have demonstrated that RM may reduce number of hospital visits, time required for patient follow-up, physician and nurse time, hospital and social costs. Furthermore, patient retention and adherence to follow-up schedule are significantly improved by RM. Continuous wireless monitoring of data stored in the device memory with automatic alerts allows early detection of device malfunctions and of events requiring clinical reaction, such as atrial fibrillation, ventricular arrhythmias and heart failure. Early reaction may improve patient outcome. RM is easy to use and patients showed a high level of acceptance and satisfaction. Implementing RM in daily practice may require changes in clinic workflow. To this purpose, new organisational models have been introduced. In spite of a favourable cost:benefit ratio, RM reimbursement still represents an issue in several European countries. PMID- 26835082 TI - The Burden of Ventricular Arrhythmias Following Left Ventricular Assist Device Implantation. AB - Few innovations in medicine have so convincingly and expeditiously improved patient outcomes more than the development of the left ventricular assist device (LVAD). Where optimal pharmacotherapy once routinely failed those with end-stage disease, the LVAD now offers considerable hope for the growing advanced heart failure population. Despite improvements in mortality, however, mechanical circulatory support is not without its limitations. Those supported with an LVAD are at increased risk of several complications, including infection, bleeding, stroke and arrhythmic events. While once considered benign, ventricular arrhythmias in the LVAD patient are being increasingly recognised for their deleterious influence on patient morbidity and quality of life. In addition, the often multifactorial aetiology to these episodes makes treatment difficult and optimal therapeutic management controversial. Novel strategies are clearly needed to better predict, prevent, and eradicate these arrhythmias in order to allow future generations of heart failure patients to reap the full benefits of LVAD implantation. PMID- 26835081 TI - The Use of Gene Therapy for Ablation of Atrial Fibrillation. AB - Atrial fibrillation is the most common clinically significant cardiac arrhythmia, increasing the risk of stroke, heart failure and morbidity and mortality. Current therapies, including rate control and rhythm control by antiarrhythmic drugs or ablation therapy, are moderately effective but far from optimal. Gene therapy has the potential to become an attractive alternative to currently available therapies for atrial fibrillation. Various gene transfer vectors have been developed for cardiovascular disease with viral vectors being most widely used due to their high efficiency. Several gene delivery methods have been employed on different therapeutic targets. With increasing understanding of arrhythmia mechanisms, novel therapeutic targets have been discovered. This review will evaluate state-of-art gene therapy strategies and approaches including sinus rhythm restoration and ventricular rate control that could eventually prevent or eliminate atrial fibrillation in patients. PMID- 26835083 TI - Arrhythmias in the Heart Transplant Patient. AB - Orthotopic heart transplantation (OHT) is currently the most effective long-term therapy for patients with end-stage cardiac disease, even as left ventricular devices show markedly improved outcomes. As surgical techniques and immunosuppressive regimens have been refined, short-term mortality caused by sepsis has decreased, while morbidity caused by repeated rejection episodes and vasculopathy has increased, and is often manifested by arrhythmias. These chronic transplant complications require early and aggressive multidisciplinary treatment. Understanding the relationship between arrhythmias and these complications in the acute and chronic stages following OHT is critical in improving patient prognosis, as arrhythmias may be the earliest or sole presentation. Finally, decentralised/ denervated hearts represent a unique opportunity to investigate the underlying mechanisms of arrhythmias. PMID- 26835084 TI - Sudden Unexplained Death - Treating the Family. AB - Sudden unexplained death in the context of a normal heart at post-mortem and negative toxicological analysis is termed sudden arrhythmic death syndrome (SADS). SADS is often due to cardiac genetic disease, particularly channelopathies. Assessment of family members of SADS victims will reveal at least one affected individual in up to half of families. Specialist evaluation begins with an expert cardiac autopsy that improves diagnostic accuracy and minimises erroneous interpretation of minor pathological findings. Retention of appropriate material for post-mortem genetic testing, 'the molecular autopsy', is recommended as this may provide a genetic diagnosis in up to a third of cases. Clinical assessment of families initially comprises 12-lead ECG with high right ventricular leads, echocardiogram and exercise testing. Additional investigations include sodium channel blocker and epinephrine provocation tests. Families with a diagnosis should be managed as per guidelines. Those with negative investigations can generally be discharged unless they are young and/or symptomatic. PMID- 26835085 TI - Ventricular Tachycardia Ablation - The Right Approach for the Right Patient. AB - Scar-related reentry is the most common mechanism of monomorphic ventricular tachycardia (VT) in patients with structural heart disease. Catheter ablation has assumed an increasingly important role in the management of VT in this setting, and has been shown to reduce VT recurrence and implantable cardioverter defibrillator (ICD) shocks. The approach to mapping and ablation will depend on the underlying heart disease etiology, VT inducibility and haemodynamic stability. This review explores pre-procedural planning, approach to ablation of both mappable and unmappable VT, and post-procedural testing. Future developments in techniques and technology that may improve outcomes are discussed. PMID- 26835086 TI - Pathophysiology and Management of Arrhythmias Associated with Atrial Septal Defect and Patent Foramen Ovale. AB - Atrial septal defects (ASDs) are among the most common of congenital heart defects and are frequently associated with atrial arrhythmias. Atrial and ventricular geometrical remodelling secondary to the intracardiac shunt promotes evolution of the electrical substrate, predisposing the patient to atrial fibrillation and other arrhythmias. Closure of an ASD reduces the immediate and long-term prevalence of atrial arrhythmias, but the evidence suggests that patients remain at an increased long-term risk in comparison with the normal population. The closure technique itself and its timing impacts future arrhythmia risk profile while subsequent transseptal access following surgical or device closure is complicated. Newer techniques combined with increased experience will help to alleviate some of the difficulties associated with optimal management of arrhythmias in these patients. PMID- 26835087 TI - Three-dimensional Rotational Angiography as a Periprocedural Imaging Tool in Atrial Fibrillation Ablation. AB - Atrial fibrillation (AF) ablation relies increasingly on three-dimensional (3D) visualisation tools to help guide an operator in performing a procedure safely and successfully. Current generation non-fluoroscopic navigation systems can be used as stand-alone tools, but also offer the capability to integrate information from additional imaging studies in order to enhance 3D model accuracy. Between available imaging modalities, 3D rotational angiography offers a set of interesting features such as near realtime availability, applicability in high volume workflows, integration with other imaging systems (fluoroscopic or non fluoroscopic) and very low incremental cost per procedure. Applicability of this imaging approach in AF ablation, as a complement or substitute to other imaging/navigation tools, is reviewed. PMID- 26835088 TI - Evaluating the Cost-effectiveness of Catheter Ablation of Atrial Fibrillation. AB - Atrial fibrillation (AF) is one of the most common cardiac conditions treated in primary care and specialty cardiology settings, and is associated with considerable morbidity, mortality and cost. Catheter ablation, typically by electrically isolating the pulmonary veins and surrounding tissue, is more effective at maintaining sinus rhythm than conventional antiarrhythmic drug therapy and is now recommended as first-line therapy. From a value standpoint, the cost-effectiveness of ablation must incorporate the upfront procedural costs and risks with the benefits of longer term improvements in quality of life (QOL) and healthcare utilisation. Here, we present a primer on cost-effectiveness analysis (CEA), review the data on cost-effectiveness of AF ablation and outline key areas for further investigation. PMID- 26835089 TI - Management of Cardiac Implantable Electronic Device Infection. AB - Despite improved preventive measures, infection associated with the use of cardiac implantable electronic devices (CIEDs) to treat often life-threatening conditions is rising at an average annual rate of almost 5 %. This rise is being driven by the increasing complexity of CIED technology and by the advancing age and co-morbidities of the patients. Although CIED infection is usually suspected based on local signs at the generator pocket site, diagnosis can be challenging in patients presenting no local manifestations or symptoms. Diagnostic methods include microbiological testing and echocardiography, and may be completed by positron emission tomography (PET)/computed tomography (CT) scan in selected cases. CIED infection requires a multidisciplinary approach in view of hardware extraction, targeted antibiotic therapy and reimplantation on an as-needed basis. Antibiotic prophylaxis targeting staphylococcal flora is recommended but the relation of these infections to medical care exposes patients to multi-resistant bacteria. New preventive measures utilising an antibacterial sleeve look promising. Treatment can be started on an empirical basis using an antistaphylococcal agent but must be continued using targeted antibiotic therapy. Crucial questions remain as to the best prevention strategy, optimal duration and timing of antibiotic therapy, and the most effective reimplantation technique. PMID- 26835090 TI - Cardiac Resynchronisation Therapy or MitraClip(r) Implantation for Patients with Severe Mitral Regurgitation and Left Bundle Branch Block? AB - Secondary or functional mitral regurgitation (FMR) is a common problem in patients with chronic heart failure (HF). About one-third of patients with chronic HF also have left bundle branch block (LBBB). Approximately one-third of patients with an indication for cardiac resynchronisation therapy (CRT) have moderate-to-severe FMR. This FMR may either be a consequence of systolic dysfunction or it may occur due to dyssynchrony. Both directly reducing FMR and correcting cardiac dyssynchrony are viable therapeutic approaches in selected patients, according to the 2012 European Society of Cardiology (ESC) Guidelines for valvular heart disease. Initial presence of FMR is an independent predictor of lack of clinical response to CRT. Patients undergoing CRT without signs of significant clinical improvement may be considered candidates for the percutaneous MitraClip(r) procedure. As yet, there are not enough data to select patients that would benefit from being treated primarily with MitraClip. A clinical trial in HF patients to be randomised to either MitraClip procedure or CRT is needed to confirm actual ESC Guideline therapy. PMID- 26835092 TI - Arrhythmia & Electrophysiology Review - A New Era for NOAC Antidotes. PMID- 26835091 TI - Stroke Prevention in Atrial Fibrillation - Outcomes and Future Directions. AB - Stroke prevention is central to the management of patients with atrial fibrillation (AF). Vitamin K antagonists (VKAs) are the established and long standing option for stroke prevention therapy in patients with AF. However, non VKA oral anticoagulants (NOACs) have recently been developed and demonstrated non inferior efficacy vs VKA treatment, with fewer limitations in clinical practice and with reduced risks of major bleeding. In order to discuss the usage, efficacy and safety of NOACs, a satellite symposium was held at the Cardiostim/ EHRA Europace Congress in Nice in June 2014. At present, three NOACs, a direct thrombin inhibitor (dabigatran) and two direct factor Xa inhibitors (rivaroxaban and apixaban) have been approved in Europe for stroke prevention in patients with AF. In addition, the once-daily factor Xa inhibitor edoxaban has recently been evaluated in this setting in the phase III Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation - Thrombolysis In Myocardial Infarction Study 48 (ENGAGE AF-TIMI 48) that compared edoxaban 30 mg once daily (low-dose regimen) with dose-adjusted warfarin (international normalised ratio 2.0-3.0). ENGAGE AF-TIMI 48 was the largest trial with a NOAC to date, and demonstrated that both dosing regimens of once-daily edoxaban were non-inferior to well managed warfarin treatment for the prevention of stroke or systemic embolism and also provided significant reductions in the risk of haemorrhagic stroke, cardiovascular mortality, major bleeding and intracranial bleeding. In summary, the recent availability of NOACs has enabled physicians to avoid the limitations of VKA therapy in clinical practice and tailor anticoagulant treatment to the individual patient. However, worldwide usage of oral anticoagulant therapy remains suboptimal compared with guideline recommendations, and further dissemination of its benefits may prove helpful. PMID- 26835093 TI - HCN4, Sinus Bradycardia and Atrial Fibrillation. AB - Based on their established role in the generation of spontaneous activity in pacemaker cells and control of cardiac rate, funny/ hyperpolarisation-activated, cyclic nucleotide gated 4 (HCN4) channels are natural candidates in the search for causes of sinus arrhythmias. Investigation of funny current-related inheritable arrhythmias has led to the identification of several mutations of the HCN4 gene associated with bradycardia and/or more complex arrhythmias. More recently, the search has been extended to include auxiliary proteins such as the minK-related peptide 1 (MiRP1) beta-subunit. All mutations described so far are loss-of-function and in agreement with the role of funny channels, the predominant type of arrhythmia found is bradycardia. Funny channel-linked arrhythmias, however, also include atrioventricular (AV) block and atrial fibrillation, in agreement with an emerging new concept according to which defective funny channels have a still unexplored role in impairing AV conduction and triggering atrial fibrillation. Also, importantly, recent work shows that HCN4 mutations can be associated with cardiac structural abnormalities. In this short review I briefly address the current knowledge of funny/HCN4 channel mutations and associated sinus and more complex arrhythmias. PMID- 26835094 TI - Obstructive Sleep Apnoea and Atrial Fibrillation. AB - Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia and is associated with significant morbidity and mortality. Obstructive sleep apnoea (OSA) is common among patients with AF. Growing evidence suggests that OSA is associated with the initiation and maintenance of AF. This association is independent of obesity, body mass index and hypertension. OSA not only promotes initiation of AF but also has a significant negative impact on the treatment of AF. Patients with untreated OSA have a higher AF recurrence rate with drug therapy, electrical cardioversion and catheter ablation. Treatment with continuous positive airway pressure (CPAP) has been shown to improve AF control in patients with OSA. In this article, we will review and discuss the pathophysiological mechanisms of OSA that may predispose OSA patients to AF as well as the standard and emerging therapies for patients with both OSA and AF. PMID- 26835095 TI - Contemporary Mapping Techniques of Complex Cardiac Arrhythmias - Identifying and Modifying the Arrhythmogenic Substrate. AB - Cardiac electrophysiology has moved a long way forward during recent decades in the comprehension and treatment of complex cardiac arrhythmias. Contemporary electroanatomical mapping systems, along with state-of-the-art technology in the manufacture of electrophysiology catheters and cardiac imaging modalities, have significantly enriched our armamentarium, enabling the implementation of various mapping strategies and techniques in electrophysiology procedures. Beyond conventional mapping strategies, ablation of complex fractionated electrograms and rotor ablation in atrial fibrillation ablation procedures, the identification and modification of the underlying arrhythmogenic substrate has emerged as a strategy that leads to improved outcomes. Arrhythmogenic substrate modification also has a major role in ventricular tachycardia ablation procedures. Optimisation of contact between tissue and catheter and image integration are a further step forward to augment our precision and effectiveness. Hybridisation of existing technologies with a reasonable cost should be our goal over the next few years. PMID- 26835096 TI - Biology of the Sinus Node and its Disease. AB - The sinoatrial node (SAN) is the normal pacemaker of the heart and SAN dysfunction (SND) is common, but until recently the pathophysiology was incompletely understood. It was usually attributed to idiopathic age-related fibrosis and cell atrophy or ischaemia. It is now evident that changes in the electrophysiology of the SAN, known as electrical remodelling, is an important process that has been demonstrated in SND associated with heart failure, ageing, diabetes, atrial fibrillation and endurance exercise. Furthermore, familial SND has been identified and mutations have been characterised in key pacemaker genes of the SAN. This review summarises the current evidence regarding SAN function and the pathophysiology of SND. PMID- 26835097 TI - What is a Ca(2+) wave? Is it like an Electrical Wave? AB - Arrhythmia subcellular mechanisms are constantly being explored. Recent knowledge has shown that travelling Ca(2+) waves in cardiac cells are critical for delayed afterdepolarisations and in some cases, early afterdepolarisations. In this review, we comment on the properties of cardiac Ca(2+) waves and abnormal Ca(2+) releases in terms of properties used to describe electrical waves; propagation, excitability and refractoriness. PMID- 26835098 TI - Science Linking Pulmonary Veins and Atrial Fibrillation. AB - Over the past few decades, significant progress has been made in understanding the mechanistic basis of atrial fibrillation (AF). One of the most important discoveries in this context has been that pulmonary veins (PV) play a prominent role in the pathogenesis of AF. PV isolation has since become the most widely used technique for treatment of paroxysmal AF. Multiple studies have demonstrated that the electrophysiological and anatomical characteristics of PVs create a proarrhythmogenic substrate. The following review discusses the mechanistic links between PVs and AF. PMID- 26835099 TI - Optimal Anticoagulation Strategy for Cardioversion in Atrial Fibrillation. AB - For many patients with symptomatic atrial fibrillation, cardioversion is performed to restore sinus rhythm and relieve symptoms. Cardioversion carries a distinct risk for thromboembolism which has been described to be in the order of magnitude of 1 to 3 %. For almost five decades, vitamin K antagonist therapy has been the mainstay of therapy to prevent thromboembolism around the time of cardioversion although not a single prospective trial has formally established its efficacy and safety. Currently, three new direct oral anticoagulants are approved for stroke prevention in patients with non-valvular atrial fibrillation. For all three, there are data regarding its usefulness during the time of electrical or pharmacological cardioversion. Due to the ease of handling, their efficacy regarding stroke prevention, and their safety with respect to bleeding complications, the new direct oral anticoagulants are endorsed as the preferred therapy over vitamin K antagonists for stroke prevention in non-valvular atrial fibrillation including the clinical setting of elective cardioversion. PMID- 26835100 TI - Role of Rotors in the Ablative Therapy of Persistent Atrial Fibrillation. AB - Atrial fibrillation (AF) ablation is increasingly used to maintain sinus rhythm yet its results are sub-optimal, especially in patients with persistent AF or prior unsuccessful procedures. Attempts at improvement have often targeted substrates that sustain AF after it is triggered, yet those mechanisms are debated. Many studies now challenge the concept that AF is driven by self sustaining disordered wavelets, showing instead that localised drivers (rotors) may drive disorder via a process known as fibrillatory conduction. Novel mapping using wide-area recordings, physiological filtering and phase analysis demonstrates rotors in human AF. Contact mapping with focal impulse and rotor modulation (FIRM) shows that localised ablation at sources can improve procedural success in many populations on long-term follow up and some newer approaches to rotor mapping are qualitatively similar. This review critically evaluates the data on rotor mapping and ablation, which advances our conceptual understanding of AF and holds the promise of substantially improving ablative outcomes in patients with persistent AF. PMID- 26835101 TI - Management of Cardiovascular Implantable Electronic Devices Infections in High Risk Patients. AB - The incidence of infection following implantation of cardiovascular implantable electronic devices (CIEDs) is increasing, as is the number of pulse generator replacements and upgrades. The rate of infections is rising faster than the rate of device implantation, mainly due to the increasing age and number of comorbidities of patients receiving the devices. Patients with a CIED infection usually require hospitalisation, multiple consultations, prolonged intravenous antibiotics and, in the majority of cases, CIED explantation and replacement. A significant proportion die of their infection. CIED infection therefore represents a substantial health and economic burden, and management of infections is critical. Numerous risk factors have been identified including host, procedure and device-related factors. Established strategies for preventing CIED infections include intravenous antibiotics and aseptic techniques. The TYRXTM Absorbable Antibacterial Envelope offers potential as an effective method to reduce CIED infections. Several studies have found a statistically significant association between antibacterial envelope use and reduced incidence of CIED infection in high-risk patients. A prospective, randomised trial to further evaluate this potentially important strategy for CIED infection prophylaxis is underway. PMID- 26835102 TI - Balloon Devices for Atrial Fibrillation Therapy. AB - Ablation of atrial fibrillation (AF) is an established treatment option for symptomatic patients refractory to antiarrhythmic medication. In patients with paroxysmal AF, ablation can be offered as first-line therapy when performed in an experienced centre. The accepted cornerstone for all ablation strategies is isolation of the pulmonary veins. However, it is still challenging to achieve contiguous, transmural, permanent lesions using radio-frequency current (RFC) based catheters in conjunction with a three-dimensional mapping system and the learning curve remains long. These limitations have kindled interest in developing and evaluating novel catheter designs that incorporate alternative energy sources. Novel catheters include balloon-based ablation systems, incorporating different energy modalities such as laser (Heartlight(TM), CardioFocus, Marlborough, MA, US), RFC (Hot Balloon Catheter, Hayama Arrhythmia Institute, Kanagawa, Japan) and cryo-energy (ArcticFront, Medtronic, Inc., Minneapolis, MN, US). While the cryoballoon (CB) and the radiofrequency hot balloon (RHB) are single-shot devices, the endoscopic ablation system (EAS) allows for point-by-point ablation. The CB and EAS are well established as safe, time-efficient and effective ablation tools. Initial studies using the RHB could also demonstrate promising results. However, more data are required. PMID- 26835104 TI - What is Established and What is New in Ablation of Persistent Atrial Fibrillation? PMID- 26835103 TI - Computer Modelling for Better Diagnosis and Therapy of Patients by Cardiac Resynchronisation Therapy. AB - Mathematical or computer models have become increasingly popular in biomedical science. Although they are a simplification of reality, computer models are able to link a multitude of processes to each other. In the fields of cardiac physiology and cardiology, models can be used to describe the combined activity of all ion channels (electrical models) or contraction-related processes (mechanical models) in potentially millions of cardiac cells. Electromechanical models go one step further by coupling electrical and mechanical processes and incorporating mechano-electrical feedback. The field of cardiac computer modelling is making rapid progress due to advances in research and the ever increasing calculation power of computers. Computer models have helped to provide better understanding of disease mechanisms and treatment. The ultimate goal will be to create patient-specific models using diagnostic measurements from the individual patient. This paper gives a brief overview of computer models in the field of cardiology and mentions some scientific achievements and clinical applications, especially in relation to cardiac resynchronisation therapy (CRT). PMID- 26835105 TI - Mechanisms of Heart Block after Transcatheter Aortic Valve Replacement - Cardiac Anatomy, Clinical Predictors and Mechanical Factors that Contribute to Permanent Pacemaker Implantation. AB - Transcatheter aortic valve replacement (TAVR) has emerged as a valuable, minimally invasive treatment option in patients with symptomatic severe aortic stenosis at prohibitive or increased risk for conventional surgical replacement. Consequently, patients undergoing TAVR are prone to peri-procedural complications including cardiac conduction disturbances, which is the focus of this review. Atrioventricular conduction disturbances and arrhythmias before, during or after TAVR remain a matter of concern for this high-risk group of patients, as they have important consequences on hospital duration, short- and long-term medical management and finally on decisions of device-based treatment strategies (pacemaker or defibrillator implantation). We discuss the mechanisms of atrioventricular disturbances and characterise predisposing factors. Using validated clinical predictors, we discuss strategies to minimise the likelihood of creating permanent high-grade heart block, and identify factors to expedite the decision to implant a permanent pacemaker when the latter is unavoidable. We also discuss optimal pacing strategies to mitigate the possibility of pacing induced cardiomyopathy. PMID- 26835106 TI - Arrhythmogenic Right Ventricular Cardiomyopathy - Antiarrhythmic Therapy. AB - Arrhythmogenic right ventricular cardiomyopathy is an inherited disorder characterised by progressive replacement of ventricular myocardium by fibrofatty tissue that predisposes patients to ventricular arrhythmias, heart failure and sudden death. Treatment focuses on slowing disease progression, decreasing the burden of arrhythmias and preventing sudden cardiac death through placement of implantable cardioverter-defibrillators (ICDs), catheter ablation and the use of antiarrhythmic medication. Although only ICDs have been demonstrated to affect patient mortality, antiarrhythmic medications are important adjuncts in reducing patient morbidity and inappropriate ICD therapy. Of the individual antiarrhythmic agents available, sotalol, beta-blockers and amiodarone appear to be most effective in arrhythmia suppression. Calcium-channel blockers may be effective in selected patients. For patients who are refractory to single agent therapy, combination therapy may be considered with the most effective combinations being sotalol + flecainide and amiodarone + beta-blockers. PMID- 26835107 TI - Monitoring the Effects and Antidotes of the Non-vitamin K Oral Anticoagulants. AB - In the last decade, we have witnessed the emergence of the oral non-vitamin K oral anticoagulants (NOACs), which have numerous advantages compared with the vitamin K antagonists, particularly their lack of need for monitoring; as a result their use is increasing. Nonetheless, the NOACs face two major challenges: the need for reliable laboratory assays to assess their anticoagulation effect, and the lack of approved antidotes to reverse their action. This article provides an overview of monitoring the anticoagulant effect of NOACs and their potential specific antidotes in development. PMID- 26835108 TI - Early Repolarisation - What Should the Clinician Do? AB - The early repolarisation (ER) pattern is a common ECG finding. Most individuals with the ER pattern are at minimal risk for arrhythmic events. In others, ER increases the arrhythmic risk of underlying cardiac pathology. Rarely ER syndrome will manifest as a primary arrhythmogenic disorder causing ventricular fibrillation (VF). ER syndrome is defined as syncope attributed to ventricular arrhythmias or cardiac arrest attributed to ER following systematic exclusion of other etiologies. Some ECG features associated with ER portend a higher risk. However, clinically useful risk-stratifying tools to identify the asymptomatic patient at high risk are lacking. Patients with asymptomatic ER and no family history of malignant ER should be reassured. All patients with ER should continue to have modifiable cardiac risk factors addressed. Symptomatic patients should be systematically investigated, directed by symptoms. PMID- 26835110 TI - A Decade of CFAE Mapping: Still Seeking More Specific Tools to Identify Sources and Substrate of Persistent Atrial Fibrillation. PMID- 26835109 TI - Anticoagulation in Atrial Fibrillation - Current Concepts. AB - This article presents the current status of the use of anticoagulation for the treatment of AF, particularly with the use of non-vitamin K-dependent anticoagulants. Comparisons between these agents and warfarin are made and methods for assessment of anticoagulant activity and reversal are discussed. PMID- 26835112 TI - The Entirely Subcutaneous Defibrillator - A New Generation and Future Expectations. AB - Although conventional implantable cardioverter-defibrillators (ICDs) have proved effective in the prevention of sudden cardiac death (SCD), they still appear to be limited by non-trivial acute and long-term complications. The recent advent of an entirely subcutaneous ICD (S-ICD) represents a further step in the evolution of defibrillation technology towards a less-invasive approach. This review highlights some historical and current issues concerning the S-ICD that may offer a viable therapeutic option in selected patients at high risk of SCD and in whom pacing is not required. After the CE Mark and US Food and Drug Administration (FDA) approvals, the S-ICD is being implanted worldwide with growing clinical data regarding its safety and efficacy (the EFFORTLESS Registry). The recently developed new generation of S-ICD (EMBLEM, Boston Scientific) demonstrates favourable features including a smaller device, longer longevity and remote monitoring compatibility. Further innovations in the S-ICD system and potential integration with leadless pacing may play an important role in defibrillation therapy and prevention of SCD in the near future. PMID- 26835111 TI - Is Mapping of Complex Fractionated Electrograms Obsolete? AB - Atrial fibrillation is the most common clinically encountered arrhythmia and catheter ablation has emerged as a viable treatment option in drug-refractory cases. Pulmonary vein isolation is widely regarded as the cornerstone for successful outcomes in paroxysmal AF given that the pulmonary veins are a frequent source of AF triggering. Ablation strategies for persistent AF are less well defined. Mapping and ablation of complex fractionated electrograms (CFAEs) is one strategy that has been proposed as a means of modifying the atrial substrate thought to be critical to the perpetuation of AF. Results of clinical studies have proved conflicting and there are now strong data to suggest that pulmonary vein isolation alone is associated with outcomes comparable to those of pulmonary vein isolation plus CFAE ablation. Several studies have demonstrated that the majority of CFAEs are passive phenomena and therefore not critical to the perpetuation of AF. Conventional mapping technologies (using a bipolar or circular mapping catheter) lack the spatiotemporal resolution to identify mechanisms of AF persistence. The development of wide-field mapping techniques allows simultaneous acquisition of activation data over large areas. This strategy has the potential to better identify regions critical to AF perpetuation, and preliminary data suggest that ablation outcomes are improved when guided by these techniques. While mapping and ablation of all CFAEs is almost certainly obsolete, better identification of regions responsible for AF persistence has the potential to improve outcomes in ablation of persistent AF. PMID- 26835115 TI - Widening our Circle of Influence. PMID- 26835113 TI - Developments in Cardiac Resynchronisation Therapy. AB - Cardiac resynchronisation therapy (CRT) is an important therapy for patients with heart failure with a reduced ejection fraction and interventricular conduction delay. Large trials have established the role of CRT in reducing heart failure hospitalisations and improving symptoms, left ventricular (LV) function and mortality. Guidelines from major medical societies are consistent in support of CRT for patients with New York Health Association (NYHA) class II, III and ambulatory class IV heart failure, reduced LV ejection fraction and QRS prolongation, particularly left bundle branch block. The current challenge facing practitioners is to maximise the rate of patients who respond to CRT and the magnitude of that response. Current areas of interest for achieving these goals include tailoring patient selection, individualising LV lead placement and application of new technologies and techniques for CRT delivery. PMID- 26835114 TI - Sex Differences in Utilisation and Response to Implantable Device Therapy. AB - Multiple studies have demonstrated that implantable cardioverter-defibrillators (ICDs) and cardiac resynchronisation therapy (CRT) provide significant mortality and morbidity benefits to eligible patients irrespective of gender. However, female patients are less likely to receive this life-saving therapy and are significantly under-represented in cardiac device trials. Various performance improvement programmes have proved that this gender disparity can be reduced and these therapies should be offered to all eligible patients regardless of sex. Efforts should be made to enrol more women in clinical trials and sex-specific analysis in medical device clinical studies should be encouraged. In this article we review the data on sex differences in clinical outcomes with ICDs and CRT and explore the reasons for this sex-based disparity. PMID- 26835116 TI - Clinical Electrophysiology and Precision Medicine Initiatives. PMID- 26835117 TI - The Role of MicroRNAs in Antiarrhythmic Therapy for Atrial Fibrillation. AB - Atrial fibrillation (AF) is the most common arrhythmia worldwide and has an enormous impact on our healthcare system as it is a major contributor of morbidity and mortality. Although there are several therapeutic options available, treatment of AF still remains challenging. AF pathophysiology is complex and still incompletely understood. In general, our understanding of AF is based on two mechanistic paradigms as functional hallmarks of AF: ectopic activity and reentry. Both ectopic activity and reentry are the result of remodelling processes. Functional and/or expressional changes in ion channels, connexins or calcium-handling proteins are important factors in electrical remodelling, whereas signalling processes leading to atrial dilatation and atrial fibrosis are key factors of structural remodelling. In recent years, new intriguing key players in AF pathophysiology have been identified: microRNAs (miRNAs). MiRNAs are short, non-coding RNA fragments that can regulate gene expression and have been demonstrated as important modifiers in signalling cascades leading to electrical and structural remodelling. In this article we review the miRNA-mediated molecular mechanisms underlying AF with special emphasis on the perspective of miRNAs as potential therapeutic targets for AF treatment. PMID- 26835118 TI - Nature and Nurture in Arrhythmogenic Right Ventricular Cardiomyopathy - A Clinical Perspective. AB - Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterised by frequent ventricular arrhythmias and slowly progressive predominant RV dysfunction. Up to two-thirds of ARVD/C patients have mutations in genes encoding the cardiac desmosome. Mutations in other genes are increasingly recognised. Inheritance of ARVD/C is generally autosomal dominant with reduced age-related penetrance and significant variable expressivity. While the full explanation for this phenotypic heterogeneity remains unclear, there is increasing evidence that exercise plays a major role in disease penetrance and arrhythmic risk. The disproportionate representation of athletes among ARVD/C patients has long been noted. Recently, the association of exercise with earlier onset and more severe arrhythmic and structural disease has been documented. This article reviews current evidence regarding the association of genotype, exercise and clinical outcomes and discusses the emerging paradigm in which genetic predisposition and environmental factors (exercise) interact around a threshold for phenotypic expression of ARVD/C. PMID- 26835119 TI - Upstream Treatment of Atrial Fibrillation with n-3 Polyunsaturated Fatty Acids: Myth or Reality? AB - Atrial fibrillation (AF) is the most common sustained arrhythmia in adults and is associated with an increased risk of fatal and non-fatal events. Antiarrhythmic drugs provide limited protection against AF recurrence and have a poor safety profile. Several mechanisms have been proven to be involved in AF, e.g. inflammation, oxidative stress, fibrosis and ischaemia. Prevention of AF with interventions that target these mechanisms has emerged as a result of experimental studies suggesting the use of upstream therapies. Long chain n-3 polyunsaturated fatty acids (n-3 PUFA) have multiple effects on cardiac electrophysiology, and epidemiological studies on fish oil suggest a possible use of n-3 PUFA in AF prevention. Several randomised clinical trials have been designed to evaluate the efficacy of n-3 PUFA in preventing AF. In this review, we report the conflicting results of these trials in two different clinical settings: recurrence in patients with history of AF and development of post operative AF in patient undergoing cardiac surgery. PMID- 26835120 TI - Early Repolarisation Syndrome - New Concepts. AB - New concepts regarding early repolarisation syndrome are presented. Genetics and epidemiology data, as well as new evidence on the potential clinical significance of early repolarisation patterns, are discussed. PMID- 26835121 TI - Body Surface Mapping to Guide Atrial Fibrillation Ablation. AB - Atrial fibrillation (AF) is the most common rhythm disorder, and is strongly associated with thromboembolic events and heart failure. Over the past decade, catheter ablation of AF has advanced considerably with progressive improvement in success rates. However, interventional treatment is still challenging, especially for persistent and long-standing persistent AF. Recently, AF analysis using a non invasive body surface mapping technique has been shown to identify localised reentrant and focal sources, which play an important role in driving and perpetuating AF. Non-invasive mapping-guided ablation has also been reported to be effective for persistent AF. In this review, we describe new clinical insights obtained from non-invasive mapping of persistent AF to guide catheter ablation. PMID- 26835123 TI - Selecting the Appropriate Ablation Strategy: the Role of Endocardial and/or Epicardial Access. AB - Percutaneous catheter ablation has emerged as an effective treatment modality for the management of ventricular tachycardia. Despite years of progress in this field, the role of epicardial mapping and ablation needs to be further refined. In this review, we discuss the relationship between the type of underlying heart disease and the location of the arrythmogenic substrate as it pertains to a procedural approach. We describe the contribution of preprocedural and intraprocedural diagnostic tools for the localisation of the arrhythmogenic substrate, with a special emphasis on cardiac MRI and electrophysiological mapping. In our opinion, the preferred approach to target ventricular tachycardia should depend on the patient's underlying heart disease and the location of scar tissue, which can be best visualised using cardiac MRI. PMID- 26835122 TI - Long-term Outcomes of Ventricular Tachycardia Ablation in Different Types of Structural Heart Disease. AB - Ventricular tachycardia (VT) often occurs in the setting of structural heart disease and can affect patients with ischaemic or nonischaemic cardiomyopathies. Implantable cardioverter-defibrillators (ICDs) provide mortality benefit and are therefore indicated for secondary prevention in patients with sustained VT, but they do not reduce arrhythmia burden. ICD shocks are associated with increased morbidity and mortality, and antiarrhythmic medications are often used to prevent recurrent episodes. Catheter ablation is an effective treatment option for patients with VT in the setting of structural heart disease and, when successful, can reduce the number of ICD shocks. However, whether VT ablation results in a mortality benefit remains unclear. We aim to review the long-term outcomes in patients with different types of structural heart disease treated with VT ablation. PMID- 26835124 TI - Syncope in Patients with Pacemakers. AB - Syncope in a pacemaker patient is a serious symptom but it is rarely due a pacemaker system malfunction. Syncope occurs in about 5 % of patients paced for atrioventricular (AV) block in 5 years, 18% in those paced for sinus node disease in 10 years, 20 % of those paced for carotid sinus syndrome in 5 years and 5-55 % of those older patients paced for vasovagal syncope in 2 years. The vastly different results in vasovagal syncope depend on the results of tilt testing, where those with negative tests approach results in pacing for AV block and those with a positive tilt test show no better results than with no pacemaker. The implication of tilt results is that a hypotensive tendency is clearly demonstrated by tilt positivity pointing to syncope recurrence with hypotension. This problem may be addressed by treatment with vasoconstrictor drugs in those who are suited or, more commonly, a reduction or cessation of hypotensive therapy in hypertensive patients. Other causes of syncope such as tachyarrhythmias are rare. The clinical approach to patients who report syncope is detailed. PMID- 26835125 TI - Gemcitabine and Chlorotoxin Conjugated Iron Oxide Nanoparticles for Glioblastoma Therapy. AB - Many small-molecule anti-cancer drugs have short blood half-lives and toxicity issues due to non-specificity. Nanotechnology has shown great promise in addressing these issues. Here, we report the development of an anti-cancer drug gemcitabine-conjugated iron oxide nanoparticle for glioblastoma therapy. A glioblastoma targeting peptide, chlorotoxin, was attached after drug conjugation. The nanoparticle has a small size (~32 nm) and uniform size distribution (PDI ~ 0.1), and is stable in biological medium. The nanoparticle effectively enter cancer cells without losing potency compared to free drug. Significantly, the nanoparticle showed a prolonged blood half-life and the ability to cross the blood-brain barrier in wild type mice. PMID- 26835126 TI - Organizing pneumonia associated with M ycobacterium tuberculosis infection. AB - Organizing pneumonia is an inflammatory lung disease involving the distal bronchioles, respiratory bronchioles, bronchiolar ducts, and alveoli. A number of viral and bacterial organisms have been identified as causative agents of organizing pneumonia. However, M ycobacterium tuberculosis has rarely been reported as a causative agent. Herein, we report our experience with two patients diagnosed with pulmonary tuberculosis, whose biopsies showed patterns associated with organizing pneumonia. Both patients showed positive results for bacteriological tests and presence of acid fast bacilli. Hence, we could successfully treat both patients with anti-tuberculosis medications. Our report suggests that M . tuberculosis infection could be added to the list of infectious conditions associated with organizing pneumonia. PMID- 26835127 TI - Goal-dependent current compensation and drift in surf scoter flocks. AB - BACKGROUND: Animals moving through air or water toward a goal frequently must contend with fluid currents, which can drift the actual path of the animal away from the direction of heading. Whether, and to what degree, animals compensate for currents depends on the species and environmental context, but plays an important role in the movement ecology of the species. In this paper, flocks of surf scoters (Melanitta perspicillata), an aquatic diving duck, were individually tracked during collective foraging in the presence of sideward water currents to assess the individual compensatory response while moving from open water toward the foraging location versus return to open water. RESULTS: During short-range movement toward the foraging location, surf scoters moved more slowly, and compensated for currents by orienting diagonally into the current to maintain a perpendicular track to the goal. In contrast, during return to open water, surf scoters moved faster, and maintained a perpendicular orientation away from the foraging location, and allowed the sideward current to drift their track diagonally. CONCLUSIONS: Surf scoters show a behavioural flexibility in response to currents, alternately using compensation and drift as the movement goal and consequent cost of accuracy change. PMID- 26835128 TI - Effects of conditioning hops on drop jump and sprint performance: a randomized crossover pilot study in elite athletes. AB - BACKGROUND: It has previously been shown that conditioning activities consisting of repetitive hops have the potential to induce better drop jump (DJ) performance in recreationally active individuals. In the present pilot study, we investigated whether repetitive conditioning hops can also increase reactive jump and sprint performance in sprint-trained elite athletes competing at an international level. METHODS: Jump and sprint performances of 5 athletes were randomly assessed under 2 conditions. The control condition (CON) comprised 8 DJs and 4 trials of 30-m sprints. The intervention condition (HOP) consisted of 10 maximal repetitive two legged hops that were conducted 10 s prior to each single DJ and sprint trial. DJ performance was analyzed using a one-dimensional ground reaction force plate. Step length (SL), contact time (CT), and sprint time (ST) during the 30-m sprints were recorded using an opto-electronic measurement system. RESULTS: Following the conditioning activity, DJ height and external DJ peak power were both significantly increased by 11 % compared to the control condition. All other variables did not show any significant differences between HOP and CON. CONCLUSIONS: In the present pilot study, we were able to demonstrate large improvements in DJ performance even in sprint-trained elite athletes following a conditioning activity consisting of maximal two-legged repetitive hops. This strengthens the hypothesis that plyometric conditioning exercises can induce performance enhancements in elite athletes that are even greater than those observed in recreationally active athletes.. In addition, it appears that the transfer of these effects to other stretch-shortening cycle activities is limited, as we did not observe any changes in sprint performance following the plyometric conditioning activity. PMID- 26835129 TI - Prevalence and risk factors of low back pain among operation room staff at a Tertiary Care Center, Makkah, Saudi Arabia: a cross-sectional study. AB - BACKGROUND: Low Back Pain (LBP) is the commonest musculoskeletal disorder and an important occupational hazard among healthcare workers (HCWs) that peaks among Operating Room (OR) staff. This cross-sectional study aimed to assess the prevalence, characteristics, and risk factors of low back pain among operating room (OR) staff in a tertiary healthcare center in Makkah, Saudi Arabia. METHODS: A 39-item self-administered questionnaire was distributed to all available OR staff. Data about personal, sociodemographic, general risk factors OR specific risky activities, and LBP characteristics were obtained. Descriptive, crosstabs, and univariate and multivariate logistic regression tests were employed. RESULTS: Out of the 143 distributed questionnaires, 84 % were received. LBP prevalence was 74.2 %. No statistically significant associations were detected between LBP and any of the general risk factors (p >0.05). However, most of the OR risky activities were significantly associated with the occurrence of LBP (p <0.05) e.g. lifting objects above the waist, rotating torso while bearing weight, transferring patients onto bed or chair, pulling a patient up the bed, and repositioning a patient in bed. These significant associations were preserved after adjustment for gender, perceived stress at work, educational level, and receiving education about LBP. Rest and analgesics were reported to be the most common relievers. CONCLUSIONS: LBP is a common health issue among KAMC OR staff. OR risky activities were found to contribute to this problem. We suggest designing educational interventional programs to teach OR staff the best way to prevent this problem. PMID- 26835131 TI - Correction. AB - [This corrects the article DOI: 10.1136/bmjresp-2014-000049.]. PMID- 26835130 TI - The relationship between night work and involuntary weight change: data from the fifth Korea National Health and Nutrition Examination Survey (KNHANES 2010-2012). AB - BACKGROUND: Previous studies on the association between shift or night work and weight change have been focused on finding the risk of weight gain caused by shift or night work. In this study, we aimed to reveal the risk of weight gain and weight loss associated with night work by using a nationwide representative data. METHODS: This study was performed on 1605 full-time wage workers between the age of 20 and 69 based on the fifth Korea National Health and Nutrition Examination Survey (KNHANES 2010-2012). The association between night work and involuntary weight change in the previous year was divided into the categories of weight gain and weight loss and studied with modifications in socio-demographic variables, health behavior-related variables, and occupational characteristic variables. RESULTS: The participants working in night work accounted for 10.6 % of total study participants (male; 11.9 %, female 7.4 %). Workers who worked more than 48 hours per week on average accounted for 41.6 % of the total study participants (male; 46.3 %, female 29.1 %). Odds ratio (OR) of weight loss associated with night work in male workers was 0.34 (95 % confidence interval (CI) 0.16-0.76) after controlling for several related factors. OR of weight loss associated with night work in female workers with long working hours was 1.95 (95 % CI 0.47-80.86) and that of weight gain was 2.83 (95 % CI 0.12-69.83) after adjusting associated factors. CONCLUSIONS: In this cross-sectional study with national representative sample, night work may lower the risk of weight loss in male workers and induce weight change (weight loss or weight gain) in female workers with long working hours. Therefore, future studies with cohort study design for night workers are needed to reveal the mechanisms and health effects of weight change associated with night work and establish proper management solutions with health and labor policies for Korean night workers. PMID- 26835132 TI - Comparative study of linear and curvilinear ultrasound probes to assess quadriceps rectus femoris muscle mass in healthy subjects and in patients with chronic respiratory disease. AB - INTRODUCTION: Ultrasound measurements of rectus femoris cross-sectional area (RFCSA) are clinically useful measurements in chronic obstructive pulmonary disease (COPD) and critically ill patients. Technical considerations as to the type of probe used, which affects image resolution, have limited widespread clinical application. We hypothesised that measurement of RFCSA would be similar with linear and curvilinear probes. METHODS: Four studies were performed to compare the use of the curvilinear probe in measuring RFCSA. Study 1 investigated agreement of RFCSA measurements using linear and curvilinear probes in healthy subjects, and in patients with chronic respiratory disease. Study 2 investigated the intra-rater and inter-rater agreement using the curvilinear probe. Study 3 investigated the agreement of RFCSA measured from whole and spliced images using the linear probe. Study 4 investigated the applicability of ultrasound in measuring RFCSA during the acute and recovery phases of an exacerbation of COPD. RESULTS: Study 1 showed demonstrated no difference in the measurement of RFCSA using the curvilinear and linear probes (308+/-104 mm(2) vs 320+/-117 mm(2), p=0.80; intraclass correlation coefficient (ICC)>0.97). Study 2 demonstrated high intra-rater and inter-rater reliability of RFCSA measurement with ICC>0.95 for both. Study 3 showed that the spliced image from the linear probe was similar to the whole image RFCSA (308+/-103.5 vs 263+/-147 mm(2), p=0.34; ICC>0.98). Study 4 confirmed the clinical acceptability of using the curvilinear probe during an exacerbation of COPD. There were relationships observed between admission RFCSA and body mass index (r=+0.65, p=0.018), and between RFCSA at admission and physical activity levels at 4 weeks post-hospital discharge (r=+0.75, p=0.006). CONCLUSIONS: These studies have demonstrated that clinicians can employ whole and spliced images from the linear probe or use images from the curvilinear probe, to measure RFCSA. This will extend the clinical applicability of ultrasound in the measurement of muscle mass in all patient groups. PMID- 26835133 TI - Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: integrated analysis of cumulative data from 5 clinical trials. AB - BACKGROUND: Pirfenidone is an oral antifibrotic agent that has been shown to reduce the decline in lung function in patients with idiopathic pulmonary fibrosis (IPF). We performed an integrated analysis of safety data from five clinical trials evaluating pirfenidone in patients with IPF. METHODS: All patients treated with pirfenidone in the three multinational Phase 3 studies (CAPACITY (studies 004 and 006), ASCEND (study 016)) and two ongoing open-label studies (study 002 and study 012 (RECAP)) were included in the analysis. Safety outcomes were assessed during the period from the first dose until 28 days after the last dose of study drug. RESULTS: A total of 1299 patients were included in the analysis. The cumulative total exposure to pirfenidone was 3160 person exposure years (PEY). The median duration of exposure was 1.7 years (range 1 week to 9.9 years), and the mean (+/-SD) daily dose was 2053.8 (+/-484.9) mg. Gastrointestinal events (nausea (37.6%), diarrhoea (28.1%), dyspepsia (18.4%), vomiting (15.9%)) and rash (25.0%) were the most common adverse events; these were generally mild to moderate in severity and without significant clinical consequence. Elevations in alanine aminotransferase or aspartate aminotransferase greater than three times the upper limit of normal occurred in 40/1299 (3.1%) patients (adjusted incidence, 2.3 per 100 PEY). Elevations were generally transient and reversible with dose modification or discontinuation. CONCLUSIONS: A comprehensive analysis of safety outcomes in a large and well-defined cohort of 1299 patients with IPF who were followed prospectively for up to 9.9 years demonstrated that long-term treatment with pirfenidone is safe and generally well tolerated. TRIAL REGISTRATION NUMBERS: NCT00287716, NCT00287729, NCT00662038, NCT01366209. PMID- 26835136 TI - Pirfenidone: is it tolerable? PMID- 26835134 TI - Rationale for and design of the Idiopathic Pulmonary Fibrosis-PRospective Outcomes (IPF-PRO) registry. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease characterised by progressive loss of lung function. Its clinical course is variable but ultimately fatal. There is a need for a multicentre patient registry incorporating longitudinal clinical data and biological samples to improve understanding of the natural history of IPF and contemporary practice patterns. METHODS/DESIGN: The Idiopathic Pulmonary Fibrosis-PRospective Outcomes (IPF-PRO) registry is a national IPF registry in the USA. This registry will enrol approximately 300 patients with newly diagnosed IPF over 2 years at approximately 14 tertiary pulmonary care sites. Participants will be followed for 3-5 years and will receive usual care, as defined by their physician. Clinical data from the year prior to diagnosis will be collected from medical record review on enrolment. Subsequently, data on diagnostic evaluations, pulmonary function tests, physical examinations, laboratory data and clinical events will be collected at routine clinical visits and via a call centre. Participants will complete patient-reported outcome questionnaires at enrolment and then at approximately 6-month intervals. Blood samples for cellular, genetic and transcriptomic analyses will be collected at the same intervals. RESULTS: The first results from the IPF-PRO registry will be presented in 2015. CONCLUSIONS: The IPF-PRO registry will improve understanding of the natural history of IPF, its impact on patients and current practice in the diagnosis and care of patients with IPF. The registry will establish a repository of biological samples from a well-characterised patient population for future research. CLINICAL TRIAL NUMBER: NCT01915511. PMID- 26835137 TI - Ciprofloxacin dry powder inhaler in cystic fibrosis. PMID- 26835138 TI - Association between self-stigma and self-care behaviors in patients with type 2 diabetes: a cross-sectional study. AB - OBJECTIVE: Growing qualitative evidence reveals that many patients with chronic illnesses struggle to rebuild a positive self-image after diagnosis while attempting to find a balance between their current physical status and their ongoing social duties. One factor destabilizing patients' identities is self stigma, which seems to affect their behavioral goals through decreased self efficacy. We hypothesized that self-stigma would be an independent factor, distinct from self-efficacy, for developing self-care behaviors in patients with type 2 diabetes. METHODS: We used a consecutive sample of 209 outpatients with type 2 diabetes treated by endocrinologists at two university hospitals, one general hospital and one clinic. We performed multiple linear regression analyses to test the relationship between the patients' activation levels for self-care behaviors (dependent variable) and self-stigma, self-efficacy, and depression symptoms (independent variables), adjusting for covariates involving sociodemographic and clinical characteristics. RESULTS: In a multiple linear regression model adjusted for prior covariates, there was significant association between self-stigma and activation levels for self-care behaviors in patients with type 2 diabetes (adjusted R(2)=0.26, F (12,196)=7.20, p<0.001). The standardized partial regression coefficient of self-stigma was -0.23 (p=0.001), whereas that of self-efficacy was 0.19 (p=0.007). CONCLUSIONS: Self-stigma is a negative independent factor, separate from self-efficacy, affecting the self-care behaviors of patients with type 2 diabetes. Self-stigma also has, at least, a similar impact on self-care behaviors to that of self-efficacy. To optimize treatment outcomes, patients' self-stigma should be minimized, whereas their self efficacy should be enhanced. PMID- 26835135 TI - How does rhinovirus cause the common cold cough? AB - Cough is a protective reflex to prevent aspiration and can be triggered by a multitude of stimuli. The commonest form of cough is caused by upper respiratory tract infection and has no benefit to the host. The virus hijacks this natural defence mechanism in order to propagate itself through the population. Despite the resolution of the majority of cold symptoms within 2 weeks, cough can persist for some time thereafter. Unfortunately, the mechanism of infectious cough brought on by pathogenic viruses, such as human rhinovirus, during colds, remains elusive despite the extensive work that has been undertaken. For socioeconomic reasons, it is imperative we identify the mechanism of cough. There are several theories which have been proposed as the causative mechanism of cough in rhinovirus infection, encompassing a range of different processes. Those of which hold most promise are physical disruption of the epithelial lining, excess mucus production and an inflammatory response to rhinovirus infection which may be excessive. And finally, neuronal modulation, the most convincing hypothesis, is thought to potentiate cough long after the original stimulus has been cleared. All these hypotheses will be briefly covered in the following sections. PMID- 26835139 TI - Serological diagnosis of Leptospirosis in bovine serum samples using a microsphere immunoassay. AB - Leptospirosis causes significant economic loss within the cattle industry worldwide. Current diagnostic methods are generally inadequate for dealing with large numbers of samples, are outdated, and provide little useful diagnostic and epidemiological information. This aim of this study was to apply a microsphere immunoassay (MIA), utilising Luminex xMap technology, to 200 bovine serum samples to determine this method's usefulness in leptospirosis diagnosis in comparison with the current gold standard, the microscopic agglutination test (MAT). Although MAT is the most widely used laboratory test for the diagnosis of leptospirosis, its reliance on live cultures, subjective interpretation of results and an inability to differentiate between antibody classes, suggest MAT is no longer the best method for the diagnosis of leptospirosis. The results presented in this paper show that MIA was able to determine reactive from non reactive samples when compared with MAT, and was able to differentiate IgG and IgM classes of antibody. The results suggest increased sensitivity in MIA and the ability to multiplex up to 500 antigens at one time allows for significant improvements in cost-effectiveness as well as a reduced dependency on live cultures. The relatively low cost, high throughput platform and differentiation of antibody class, as shown in previous research, make this assay worthy of consideration for the diagnosis of leptospirosis in small-scale or large-scale bovine populations. PMID- 26835141 TI - A propensity matched comparison of return to work and quality of life after stenting or coronary artery bypass surgery. AB - OBJECTIVES: We sought to determine (1) return to work (RTW) rates, (2) long-term employment (>12 months postprocedure), (3) time taken to RTW, and (4) quality of life (QoL), in patients treated with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). METHODS: Questionnaires regarding RTW were sent to 689 PCI and 169 CABG patients who underwent PCI or CABG at University Hospitals of Leicester Trust, UK, from May 2012 to May 2013. QoL was also measured using the European QoL 5-dimensions questionnaire (EQ-5D). Responses from patients employed preprocedure were analysed using multivariate logistic regression. Propensity score-matching was further used to compare similar patient populations receiving PCI or CABG. RESULTS: The response rate was 38% (235 PCI and 88 CABG patients). 241 respondents (75%) were employed preprocedure. Of these 162 (93%) PCI and 51 (77%) CABG patients returned to work, whereas 147 (85%) PCI and 41 (62%) CABG patients were still employed at >12 months postprocedure. After propensity analysis, there was no significant difference between PCI and CABG patients in RTW, long-term employment, nor QoL. The median time taken to RTW was 6 weeks after PCI and 13 weeks after CABG (p=0.001). The effect remained significant after multivariate analysis (p=0.001) and propensity analysis (p=0.001). CONCLUSIONS: In this first propensity score matched study comparing RTW and QoL after PCI or CABG strict propensity matching indicates that RTW or QoL, is similar for PCI or CABG, albeit the number of matched pairs was small. There are differences, however, in delay in RTW. PMID- 26835140 TI - A time-series study of percutaneous closure of patent foramen ovale: premature adoption? AB - OBJECTIVES: To evaluate the impact of National Institute for Health and Care Excellence (NICE) guidance in January 2005 and subsequent trial evidence on the adoption of percutaneous closure of patent foramen ovale (PCPFO). METHODS: A retrospective time series study was conducted using the Inpatient Hospital Episode Statistics (HES) England. A total of 3801 patients, aged >=18 and <=60 years, who had PCPFO from 1 April 2006 to 31 March 2012 in England. Percentage change annualised (PCA) in PCPFO procedure rates between initial NICE guidance and publication of trial results was analysed. RESULTS: Between Quarter 2, 2006 and Quarter 4, 2009, 2163 PCPFO procedures were performed, with an increasing PCA of 48.4%. The procedure rate peaked before the presentation of equivocal results from the first randomised controlled trial (RCT) in late 2010, and declined between Quarter 4, 2009 and Quarter 4, 2011 (PCA=-15.3%). Of more than 2300 patients recruited to three RCTs, only 71 were recruited in English hospitals. CONCLUSIONS: PCPFO was rapidly adopted after the publication of initial NICE guidance despite the absence of RCT evidence of efficacy. Very few English patients participated in international RCTs of PCPFO, suggesting that NICE recommendations also failed to encourage the generation of RCT evidence. PMID- 26835142 TI - A prognostic scoring system for arm exercise stress testing. AB - OBJECTIVE: Arm exercise stress testing may be an equivalent or better predictor of mortality outcome than pharmacological stress imaging for the >=50% for patients unable to perform leg exercise. Thus, our objective was to develop an arm exercise ECG stress test scoring system, analogous to the Duke Treadmill Score, for predicting outcome in these individuals. METHODS: In this retrospective observational cohort study, arm exercise ECG stress tests were performed in 443 consecutive veterans aged 64.1 (11.1) years. (mean (SD)) between 1997 and 2002. From multivariate Cox models, arm exercise scores were developed for prediction of 5-year and 12-year all-cause and cardiovascular mortality and 5 year cardiovascular mortality or myocardial infarction (MI). RESULTS: Arm exercise capacity in resting metabolic equivalents (METs), 1 min heart rate recovery (HRR) and ST segment depression >=1 mm were the stress test variables independently associated with all-cause and cardiovascular mortality by step-wise Cox analysis (all p<0.01). A score based on the relation HRR (bpm)+7.3*METs 10.5*ST depression (0=no; 1=yes) prognosticated 5-year cardiovascular mortality with a C-statistic of 0.81 before and 0.88 after adjustment for significant demographic and clinical covariates. Arm exercise scores for the other outcome end points yielded C-statistic values of 0.77-0.79 before and 0.82-0.86 after adjustment for significant covariates versus 0.64-0.72 for best fit pharmacological myocardial perfusion imaging models in a cohort of 1730 veterans who were evaluated over the same time period. CONCLUSIONS: Arm exercise scores, analogous to the Duke Treadmill Score, have good power for prediction of mortality or MI in patients who cannot perform leg exercise. PMID- 26835143 TI - Effectiveness of structured, hospital-based, nurse-led atrial fibrillation clinics: a comparison between a real-world population and a clinical trial population. AB - OBJECTIVE: A previous randomised trial showed that structured, nurse-led atrial fibrillation (AF) care is superior to conventional AF care, although further research is needed to determine the outcomes of such care in a real-world setting. We compared the outcomes of patients in real-world, nurse-led, structured hospital AF clinics with the outcomes of a randomised trial of the efficacy of a nurse-led AF clinic, with respect to a composite outcome of cardiovascular-related hospitalisation and death. METHODS: All patients were referred to the AF nurse specialist by cardiologists. The AF nurse specialist provided patient education, risk-factor control and stimulated empowerment and compliance. During follow-up, treatment was adjusted according to clinical guidelines. Patient education was repeated, and compliance with medical treatment was controlled. The study size was powered as a non-inferiority study. Outcome measures were adjudicated by the same principles in both cohorts. RESULTS: A total of 596 patients from the real world and 356 patients from a clinical trial were included in this study. No significant difference between groups with respect to age, type of AF or CHA2DS2VASc score was found. The composite primary end point occurred with an incidence rate of 8.0 (95% CI 6.1 to 10.4) per 100 person-years in the real-world population and 8.3 (95% CI 6.3 to 10.9) per 100 person-years in the clinical trial, with a crude HR of 0.83 (95% CI 0.56 to 1.23). CONCLUSIONS: Structured, nurse-led, hospital-based AF care appears to be effective, and patient outcomes in an actual, hospital-based, structured AF care are as least as good as those in trial settings. PMID- 26835144 TI - The relationship between affective symptoms and hypertension-role of the labelling effect: the 1946 British birth cohort. AB - OBJECTIVES: To investigate the association between repeated measures of affective symptoms collected over 2 decades and hypertension (clinically ascertained or self-report); to test whether, among people with hypertension, affective symptoms are associated with awareness of hypertension, and to evaluate the longitudinal effects of the label of hypertension on affective symptoms. METHODS: Multivariable logistic regression, accounting for confounders and mediators, were used to test the aforementioned associations in 1683 participants from a national British cohort. RESULTS: Weak evidence of a cumulative impact of affective symptoms across adulthood on self-reported hypertension at age 60-64 years was observed (OR 1.40 (95% CI 1.10 to 1.78) and 1.19 (0.79 to 1.80) for symptoms at 1 2 time points and at 3-4 time points vs no symptoms, respectively). Study members with affective symptoms in recent times were more likely to have self-reported hypertension at age 60-64 years than those without symptoms (OR 1.47 (1.10 to 1.96)). Similar results were observed for awareness of hypertension (OR 2.00 (1.30 to 3.06)). Conversely, no associations were found with clinically ascertained hypertension. The act of labelling someone as hypertensive at age 53 years was associated with affective symptoms at age 60-64 years, independently of antihypertensive treatment and affective symptoms at the time of the diagnosis (OR 2.40 (1.32 to 4.36)). CONCLUSIONS: Our findings suggest that elevated risk of hypertension in participants with affective symptoms might be explained by awareness of hypertension and by exposure to medical attention, though not by a direct effect of affective symptoms on blood pressure. Conversely, long-term psychological consequences of the label of hypertension are observed. PMID- 26835145 TI - Heart rate never lies: interventional cardiologist and Braude's quote revised. AB - BACKGROUND: Interventional cardiologists may be immune to stress, allowing them to perform complex percutaneous interventions under pressure. OBJECTIVES: To assess heart rate (HR) variations as a surrogate marker of stress of interventional cardiologists during percutaneous cardiac procedures and in every day life. DESIGN: This is a single-centre observational study including a total of six male interventional cardiologists performing coronary interventions and pacemaker implantations. Participants were asked to record their HR with the Apple Watch Device during procedures, every-day life and control activities such as outpatient consultations, sport, marital conflicts and sexual intercourse. RESULTS: Average daily HR was 88+/-17 bpm. During work days, HR increased significantly during procedures (90+/-17 bpm) compared with days outside the cathlab (87+/-17 bpm, p=0.02). The average HR was higher during a regular week working (88+/-16 bpm) compared with weekends off (84+/-18 bpm, p=0.002). Complex cardiac procedures were associated with higher HR up to 122 bpm. Peak HR were higher during physical exertion. Of note, participants complained of hypersexuality and mania after night shifts. CONCLUSIONS: Work and especially percutaneous cardiac procedures increase HR independently of physical exertion suggesting that interventional cardiologists experience mental stress and emotions. PMID- 26835146 TI - Response to belimumab among patients with systemic lupus erythematosus in clinical practice settings: 24-month results from the OBSErve study in the USA. AB - OBJECTIVE: To examine disease activity and clinical outcomes, and describe overall patterns of systemic lupus erythematosus (SLE) care in patients who received belimumab in a real-world clinical setting. METHODS: This observational cohort study was conducted in US clinical practices. Rheumatologists (n=92) identified adults with SLE who had received >=8 infusions of belimumab plus standard of care (SoC). Physicians assessed disease outcomes at 6-month intervals using patient medical charts, for up to 24 months. The primary outcome was physician-assessed change in SLE disease. Other outcomes included change in steroid use, laboratory tests and healthcare resource utilisation (HCRU). RESULTS: Of 501 patients (intent-to-treat population (ITT)), 446 were female, mean age was 43.3 years and 98% had moderate/severe disease activity at baseline (first dose of belimumab). Data for 277 patients who completed 24 months of belimumab treatment were available. Among the ITT, a >=50% improvement in overall clinical response between baseline and month 6 was reported for 48.7% of patients; continued improvement was seen at all subsequent 6-month intervals relative to the previous timepoint. The percentage of patients with moderate/severe disease also decreased at each timepoint. At baseline, 77.0% of patients received steroids at a mean (SD) prednisone equivalent dose of 19.9 (14.39) mg/day, which decreased to 8.4 (7.35) mg/day at month 6 and 6.1 (9.31) mg/day at month 24. Abnormal laboratory values typically associated with SLE also demonstrated improvements at month 6, which continued through 24 months. HCRU decreased over the duration of the study. CONCLUSIONS: Patients with SLE who received belimumab plus SoC for up to 24 months demonstrated improvements in disease severity and laboratory values and a reduction in steroid use and HCRU as early as month 6. Improvements continued through 24 months, providing evidence of reduced disease activity among patients taking belimumab in real-world clinical practice. PMID- 26835147 TI - A multicentre, randomised controlled study of enteric-coated mycophenolate sodium for the treatment of relapsed or resistant proliferative lupus nephritis: an Asian experience. AB - OBJECTIVE: The optimal treatment of relapse or resistant lupus nephritis (LN) is still unclear. Mycophenolate might be an alternative therapy to avoid toxicities of cyclophosphamide (CYC). This study was aimed to compare enteric-coated mycophenolate sodium (EC-MPS) versus intravenous CYC as an induction therapy. METHODS: The study was a 12-month period of multicentre, open-labelled randomised controlled trial. Fifty-nine patients who had relapsed (36%) or who were resistant to previous CYC treatment (64%) and all who were biopsy-proven class III/IV, were randomised into CYC (n=32) and EC-MPS groups (n=27). The CYC group received intravenous CYC 0.5-1 g/m(2) monthly and the EC-MPS group was treated with EC-MPS 1440 mg/day for first 6 months. After induction therapy, both groups received EC-MPS 720 mg/day until the end of study at 12 months. RESULTS: The study was prematurely terminated due to high rate of serious adverse events in CYC arm. Death and serious infections were observed more in the CYC group (15.6% in CYC and 3.5% in EC-MPS; p=0.04). The early discontinuation rates, mainly from serious infections, were significantly higher in CYC group (percentage differences of 16.9; 95% CI 1.3 to 32.4). At the 12th month, both arms were comparable in terms of complete and partial remission rates (68% CYC and 71% EC MPS) and times to remission (96 days CYC and 97 days EC-MPS). Composites of unfavourable outcomes (death, doubling of serum creatinine, non-remission and intolerance to treatment) were 46.9% and 37% in CYC and EC-MPS (risk difference=9.84; p=0.44). CONCLUSIONS: EC-MPS may have comparable efficacy, but was better tolerated than CYC. EC-MPS should be an alternative choice of treatment for difficult-to-treat LN, particularly in CYC-experienced LN patients. Due to an early termination of the study, further clinical implementation could be cautiously used. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov ID#NCT01015456. PMID- 26835149 TI - The curious case of an invisible dog: a patient with non-psychiatric visual hallucinations. AB - A 74-year-old man reported experiencing hallucinations of a dog standing on his right side, following a recent episode of infective endocarditis. There was no history of reduced conscious level, psychosis or substance misuse. Neurological examination revealed an isolated right inferior quadrantopia, and the hallucinations were visible only in the area of the visual defect. A computed tomography scan confirmed a left occipital lobe infarct, congruent with the clinical signs. The infarct was deemed to be have originated from a septic embolus of his infected aortic valve and he was diagnosed with Charles Bonnet's syndrome (CBS). CBS is characterized by the presence of stereotyped visual hallucinations on a background of partial sight and in the absence of any psychotic illness. Early recognition can prevent wrongful diagnosis of a psychiatric condition, which may provide comfort to patients. Management is centred on reassurance and counselling, with medical therapies reserved only for patients experiencing distressing hallucinations. PMID- 26835148 TI - Lupus anticoagulant is the main predictor of adverse pregnancy outcomes in aPL positive patients: validation of PROMISSE study results. AB - OBJECTIVE: We previously reported that lupus anticoagulant (LAC) is the main predictor of poor pregnancy outcome in antiphospholipid antibody (aPL)-positive patients. We sought to confirm this finding in an independent group of patients who were subsequently recruited into the PROMISSE study. METHODS: The PROMISSE study is a multicentre, prospective, observational study of pregnancy outcomes in women with aPL and/or systemic lupus erythematosus (SLE) that enrolled patients from 2003 to 2015. All consecutive, aPL-positive patients from the PROMISSE study who completed their pregnancy between April 2011 and January 2015 (after the previous PROMISSE report) are included in the current report. Patients were followed monthly until delivery, and aPL was tested at first, second and third trimesters of pregnancy and at 12 weeks post partum. Adverse pregnancy outcomes (APOs) were defined as fetal death after 12 weeks of gestation, neonatal death, delivery prior to 36 weeks of gestation due to pre-eclampsia or placental insufficiency or small-for-gestational age (birth weight <5th percentile). RESULTS: Forty-four aPL-positive patients are included in this paper. Thirteen patients had APOs, which occurred in 80% of cases during the second trimester of pregnancy. LAC was present in 69% of patients with APOs compared with 27% of patients without APOs (p=0.01). No association was found between anticardiolipin antibodies (aCL) or anti-beta2 glycoprotein I antibodies (abeta2GPI) IgG or IgM positivity and APOs. Definite antiphospholipid syndrome (history of thrombosis and/or pregnancy morbidity and aPL) was found in 92% of patients with any APOs compared with 45% of patients without APOs (p=0.004). Conversely, the frequency of SLE was not statistically different between those with and without APOs (30% vs 39%). CONCLUSIONS: Our findings, in an independent group of aPL-positive patients from the PROMISSE study, confirm that LAC, but not aCL and abeta2GPI, is predictive of poor pregnancy outcomes after 12 weeks of pregnancy. TRIAL REGISTRATION NUMBER: NCT00198068. PMID- 26835150 TI - Frontal lobe tuberculoma. AB - Tuberculomas are usually infratentorial in children, and supratentorial lesions predominate in adults. We present a 4-year-old girl with multiple seizures, papilloedema and brisk reflexes. On investigation, she was found to have a large left parafalcine tuberculoma. She was treated with antitubercular treatment (ATT) and steroids. The child improved, seizures stopped and the papilloedema gradually disappeared. Follow-up magnetic resonance imaging brain after 8 months showed a mild reduction in the size of the lesion. Child is on regular follow-up. PMID- 26835151 TI - Gross right heart dilatation secondary to Ebstein's anomaly. PMID- 26835152 TI - Consecutive first-morning urine samples to measure change in the albumin-to creatinine ratio: a pilot study of a home urine collection protocol. AB - BACKGROUND: Multiple first-morning urine samples are recommended for measuring the urine albumin-to-creatinine ratio (ACR); however, this can be challenging in community-based research. METHODS: The objectives of the study are to pilot-test a home urine collection protocol and examine how the average and variance of ACR varied with the number of urine collections and time to laboratory analysis. This is a prospective observational pilot study. This study was conducted in London, Ontario, Canada at the London Health Sciences Centre (2012-2013). The patients were adults with chronic kidney disease (mean estimated glomerular filtration rate, 36 mL/min/1.73 m(2)). Participants collected a first-morning 20-mL urine sample on three consecutive days. This process was repeated after 3 months. Samples were picked up by hospital courier and analyzed for ACR on the same day; additional aliquots were analyzed after a delay of 24-48 h (stored at 4 degrees C) and 3-9 months (stored at -80 degrees C). The geometric mean of the percentage change in ACR between baseline and 3 months was calculated and compared between single samples and the average of two vs. three consecutive samples. RESULTS: Of 31 patients enrolled, 26 (83.9 %) submitted all six urine samples. The geometric mean of ACR for three consecutive samples at baseline was 87, 83, and 80 mg/mmol, and the corresponding percentage increase from baseline to 3 months was 15 % (95 % confidence interval (CI), -9 to 46 %), 33 % (95 % CI, 10 to 59 %), and 22 % (95 % CI, -6 to 57 %). Compared with single urine collections at baseline and follow-up, averaging ACR values from two consecutive first-morning urine samples improved the sample variance and reduced the required sample size to detect a given treatment effect by approximately 30 %. No further gain in statistical efficiency was achieved with three urine samples. Results were similar when the laboratory analysis was delayed by 24-48 h, but a delay of 3-9 months resulted in systematic overestimation of the ACR. Our study's generalizability is limited by its small sample size and reliance on a clinic based population from a single urban center. CONCLUSIONS: We successfully used a home urine collection protocol to obtain multiple first-morning urine samples in patients with chronic kidney disease. Statistical efficiency was improved by averaging ACR values from two consecutive first-morning urine samples at baseline and follow-up. PMID- 26835153 TI - Postural deformities in Parkinson's disease -Mutual relationships among neck flexion, fore-bent, knee-bent and lateral-bent angles and correlations with clinical predictors. AB - BACKGROUND: Various postural deformities appear during progression of Parkinson's disease (PD), but the underlying pathophysiology of these deformities is not well understood. The angle abnormalities seen in individual patients may not be due to distinct causes, but rather they may have occurred in an interrelated manner to maintain a balanced posture. METHODS: We measured the neck flexion (NF), fore bent (FB), knee-bent (KB) and lateral-bent (LB) angles in 120 PD patients, and examined their mutual relationships, and correlations with clinical predictors such as sex, age, disease duration, Hoehn and Yahr (H&Y) stage, medication dose (levodopa equivalent dose, LED; total dose of dopamine agonists, DDA). The relationship between the side of the initial symptoms and the direction of LB angle was also investigated. RESULTS: Our main findings were: (1) Significant relationships between NF and KB, NF and LB, FB and KB, KB and LB were observed. (2) NF angle was larger in males than in females, but FB, KB and LB angles showed no significant difference between the sexes. (3) FB and KB angles became larger with advancing age. (4) NF and FB angles were associated with disease duration. (5) NF, FB, KB and LB angles all increased significantly with increase of H&Y stage. (6) FB angle was significantly associated with LED, but DDA did not show a significant relationship with any of the measured angles. (7) Direction of LB angle was not associated with the side of initial symptoms. CONCLUSIONS: Postural abnormalities are interrelated, possibly to maintain a balanced posture. PMID- 26835154 TI - Freezing of gait associated with a corpus callosum lesion. AB - Freezing of gait (FoG) is a debilitating feature of Parkinson's disease and other parkinsonian disorders. This case demonstrates a variant of freezing of gait in a non-parkinsonian patient with a lesion of the anterior corpus callosum. The freezing improved with increased upper extremity sensory input, suggesting that compensatory circuits for use of somatosensory inputs from the arms to postural and locomotor centers were intact. PMID- 26835155 TI - Influence of milking frequency on genetic parameters associated with the milk production in the first and second lactations of Iranian Holstein dairy cows using random regression test day models. AB - BACKGROUND: The milk yield can be affected by the frequency of milking per day, in dairy cows. Previous studies have shown that the milk yield is increased by 6 25 % per lactation when the milking frequency is increased from 2 to 3 times per day while the somatic cell count is decreased. To investigate the effect of milking frequency (3X vs. 4X) on milk yield and it's genetic parameters in the first and second lactations of the Iranian Holstein dairy cows, a total of 142,604 test day (TD) records of milk yield were measured on 20,762 cows. RESULTS: Heritability estimates of milk yield were 0.25 and 0.19 for 3X milking frequency and 0.34 and 0.26 for 4X milking frequency throughout the first and second lactations, respectively. Repeatability estimates of milk yield were 0.70 and 0.71 for 3X milking frequency and 0.76 and 0.77 for 4X milking frequency, respectively. In comparison with 3X milking frequency, the milk yield of the first and second lactations was increased by 11.6 and 12.2 %, respectively when 4X was used (p < 0.01). CONCLUSIONS: Results of this research demonstrated that increasing milking frequency led to an increase in heritability and repeatability of milk yield. The current investigation provided clear evidences for the benefits of using 4X milking frequency instead of 3X in Iranian Holstein dairy cows. PMID- 26835157 TI - p53 Configures the G2/M Arrest Response of Nucleostemin-Deficient Cells. AB - Nucleostemin (NS) protects the genome from replication-induced DNA damage and plays an indispensable role in maintaining the continuous proliferation of both p53-wildtype and mutant cells. Yet, some outcomes of NS-deficient cells appear to be shaped by their p53 status, which stimulates conflicting claims on the role of p53 in executing the NS function. This disparity was conveniently attributed to the usual suspect of cell-type variations. To provide a definitive resolution, we investigated the interplay between NS and p53 in two pairs of isogenic cells, i.e. genetically modified mouse embryonic fibroblast (MEF) cells and HCT116 human colon cancer cells. In MEF cells, p53 deletion further compromises rather than rescues the proliferative potential of NS-depleted cells without changing their G2/M arrest fate before prophase entry. The detrimental effect of p53 loss in NS depleted MEF cells correlates with a dramatic increase of polyploid giant cells (PGCs) (up to 24%), which indicates aberrant mitosis. To determine how p53 shapes the response of cells to NS depletion at the molecular level, we showed that p53 turns on the expression of reprimo and MDM2 in NS-deficient MEF cells. In the absence of p53, NS-deficient MEF cells exhibit increased levels of phosphorylated cdc2 (Y15) protein and cyclin B1. In cancer (HCT116) cells, NS loss leads to G2/M arrest under both p53wt and p53ko conditions and increases phosphorylated cdc2 more in p53ko than in p53wt cells, as it does in MEF cells. Unlike its effect in MEF cells, NS depletion decreases tumor growth and increases the expression of reprimo and cyclin B1 in a p53-independent manner in HCT116 cells. Our data indicate that the p53 status of NS-deficient cells orchestrates how they respond to G2/M arrest in a normal vs. cancer cell distinct fashion. PMID- 26835156 TI - Tuberculosis and Cardiovascular Disease: Linking the Epidemics. AB - The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, subsets of mycobacteria actively replicate during latent tuberculosis infection (LTBI), and recent studies suggest that LTBI is associated with persistent chronic inflammation that may lead to CVD. Recent epidemiologic work has shown that the risk of CVD in persons who develop tuberculosis is higher than in persons without a history of tuberculosis, even several years after recovery from tuberculosis. Together, these data suggest that tuberculosis may play a role in the pathogenesis of CVD. Further research to investigate a potential link between tuberculosis and CVD is warranted. PMID- 26835158 TI - Ubiquitin-Specific Proteases as Druggable Targets. PMID- 26835159 TI - Stratified Weibull Regression Model for Interval-Censored Data. AB - Interval censored outcomes arise when a silent event of interest is known to have occurred within a specific time period determined by the times of the last negative and first positive diagnostic tests. There is a rich literature on parametric and non-parametric approaches for the analysis of interval-censored outcomes. A commonly used strategy is to use a proportional hazards (PH) model with the baseline hazard function parameterized. The proportional hazards assumption can be relaxed in stratified models by allowing the baseline hazard function to vary across strata defined by a subset of explanatory variables. In this paper, we describe and implement a new R package straweib, for fitting a stratified Weibull model appropriate for interval censored outcomes. We illustrate the R package straweib by analyzing data from a longitudinal oral health study on the timing of the emergence of permanent teeth in 4430 children. PMID- 26835160 TI - Association Between Specific Depression Symptoms and Glycemic Control Among Patients With Comorbid Type 2 Diabetes and Provisional Depression. AB - OBJECTIVE: To determine whether specific depression symptoms are associated with glycemic control independent of potential demographic and clinical covariates among primary care patients with comorbid type 2 diabetes and provisional threshold or subthreshold depression. METHOD: We examined a convenience sample of patients diagnosed with type 2 diabetes and provisional threshold or subthreshold depression (N = 82) at 2 family health centers. Cases were identified using a population-based registry of patients diagnosed with type 2 diabetes (ICD-9 codes 250.00 for controlled type 2 diabetes and 250.02 for uncontrolled type 2 diabetes). Data from patients with a primary care provider appointment from the beginning of April 2011 through the end of June 2012 and with at least one 9-item Patient Health Questionnaire (PHQ-9) depression screener and a glycated hemoglobin A1c (HbA1c) laboratory test between 2 weeks before and 10 weeks after PHQ-9 screening were eligible for inclusion. We defined provisional threshold or subthreshold depression using PHQ-9 scoring criteria, which were designed to yield provisional diagnostic information about major depressive disorder based on DSM-5 diagnostic criteria. RESULTS: Patients reporting higher severity of sleep problems on the PHQ-9 had significantly higher HbA1c levels (mean = 8.48, SD = 2.17) compared to patients reporting lower severity or absence of this symptom (mean = 7.19, SD = 1.34, t 48.88 = -3.13, P = .003). Problems with sleep contributed unique variance on glycemic control (beta = 0.27, P = .02) when controlling for potential clinical and demographic covariates, with those reporting more sleep difficulties having higher HbA1c levels. CONCLUSIONS: For patients with type 2 diabetes and provisional threshold or subthreshold depression, it may be prudent to aggressively address sleep problems as a potential mechanism toward improving diabetes control. PMID- 26835161 TI - Durability of Benefit From Repeated Intravenous Lidocaine Infusions in Fibromyalgia Patients: A Case Series and Literature Review. AB - Fibromyalgia is a painful disorder with no curative treatments, and available medications typically provide partial relief of pain. Reported here is the effective use of serial intravenous lidocaine infusions for the chronic management of 3 patients with fibromyalgia. The details of the infusion procedure are described, and relevant literature is reviewed. Lidocaine infusions should be considered in fibromyalgia patients who are refractory to other treatments, and a positive response to 1 infusion may justify repeated infusions for chronic management. PMID- 26835162 TI - Implications of Sensorineural Hearing Loss With Hydrocodone/Acetaminophen Abuse. AB - Sensorineural hearing loss is an infrequently recognized side effect of pain medication abuse. Chronic pain patients treated with opiates develop different degrees of tolerance to pain medications. In many cases, the tolerance becomes the gateway to a variety of cycles of overuse and unmasking of significant psychiatric morbidity and mortality. An individualized approach utilizing combined treatment modalities (including nonopiate pharmaceuticals) is expected to become the norm. Patients can now be provided with multidisciplinary care that addresses an individual's psychiatric, social, and medical needs, which requires close cooperation between physicians of varying specialties. This report describes a patient who experienced hearing loss from hydrocodone/acetaminophen abuse. PMID- 26835163 TI - Episodic Mood Changes Preceding an Exacerbation of Multiple Sclerosis. AB - Multiple sclerosis is a neurologic inflammatory disease that can manifest with psychiatric symptoms. Although depression is the most common psychiatric diagnosis in patients with multiple sclerosis, how depression develops is not fully understood. We present the case of an individual who displayed episodic mood changes preceding an exacerbation of multiple sclerosis symptoms. The clinical and research implications of this association are discussed. PMID- 26835165 TI - Demoralization. PMID- 26835164 TI - Impact of the Doctor-Patient Relationship. PMID- 26835166 TI - History of Nonsuicidal Self-Harm Behavior and General Health Care Adherence Among Primary Care Outpatients. PMID- 26835167 TI - Are We Prepared for Ebola-Like Diseases? PMID- 26835168 TI - Antipsychotic-Induced Dysphagia: A Case Report. PMID- 26835169 TI - Onset of Obsessive-Compulsive Disorder After Episode of Pachymeningitis. PMID- 26835170 TI - The Effects of Carbamazepine and Lithium Combination on Serious Aggression and Anger Outbursts in a Case of Seronegative Limbic Encephalitis. PMID- 26835171 TI - A Psychiatric Presentation of Adrenal Insufficiency: A Case Report. PMID- 26835172 TI - Outcomes of Inpatient Treatment for Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease Versus Dementia With Lewy Bodies. AB - OBJECTIVE: Most community-based studies have shown a more malignant clinical course for patients with dementia with Lewy bodies (DLB) than Alzheimer's disease (AD). We examined differences in outcomes between patients with DLB and AD hospitalized for the treatment of behavioral and psychological symptoms of dementia. METHOD: A chart review was conducted of patients with either AD or DLB hospitalized in the acute psychogeriatric ward between January 2008 and December 2011 in Kahoku-City, Ishikawa, Japan. Outcome measures were discharge destinations and time to death. A diagnosis of AD was made according to DSM-5 criteria, whereas a diagnosis of DLB was made according to the Consortium on DLB International Workshop criteria for probable DLB. Pharmacologic treatment was optimized under constant monitoring of patients. Cholinesterase inhibitors and yi gan san were tried prior to antipsychotics in DLB patients. RESULTS: The study cohort consisted of 224 patients with AD and 106 with DLB. After matching for sociodemographic factors and cognitive and physical function, it was found that antipsychotics were less frequently used during hospitalization in patients with DLB than AD (63% vs 82%, respectively, P < .01), whereas cholinesterase inhibitors (88% vs 43%, P < .001) and yi-gan san (35% vs 20%, P < .05) were more frequently used in patients with DLB. There were no significant differences in discharge destinations between the 2 groups. The 5-year cumulative survival rates were similar in the AD and DLB groups (46.4% vs 45.7%, respectively, P = .6225). CONCLUSIONS: Optimization of pharmacologic treatment during hospitalization could reduce the use of antipsychotics and improve the subsequent clinical course in DLB. PMID- 26835174 TI - Diagnosis and Treatment Procedures for Patients With Anxiety Disorders by the Psychiatric Consultation Liaison Service in a General Hospital in Germany: A Retrospective Analysis. AB - OBJECTIVE: To investigate the population of patients with anxiety disorders in a general hospital in Germany who required treatment by a consultation psychiatrist. METHOD: A retrospective investigation of psychiatric consultations concerning 119 patients with anxiety disorders (DSM-IV criteria) from January 1, 2011, to December 31, 2012, was conducted in a general hospital of the Charite Berlin, Berlin, Germany. The frequency of different anxiety disorders, the distribution of anxiety disorders among the departments of the general hospital, and the recommended treatment procedure were investigated. RESULTS: The largest group of patients with anxiety symptoms presented panic attacks. Many of these patients sought treatment in the emergency department of the hospital primarily due to their anxiety symptoms. Within the group of somatically ill patients, panic attacks were prominent, especially in patients with cardiac or respiratory diseases. Treatment procedures comprised pharmacologic and psychotherapeutic interventions. Benzodiazepines and psychoeducation were common acute treatments; antidepressants, pregabalin, and psychotherapy were recommended for long-term treatment. CONCLUSIONS: Many patients who primarily suffer from symptoms of anxiety seek treatment in a general hospital, especially in the emergency department. It is therefore very important for the individual patient as well as the health care system that the correct treatment is initiated. The consultation liaison psychiatric service within a general hospital is important to ensure the best possible diagnostic procedures as well as treatment for patients with anxiety disorders. PMID- 26835173 TI - Frequent Comorbidity and Predictors of Social Anxiety in Persons With Schizophrenia: A Retrospective Cohort Study. AB - OBJECTIVE: To determine if symptoms of social anxiety are distinct from negative symptoms of schizophrenia. METHOD: Fifty-three patients with schizophrenia or schizoaffective disorder (diagnosed per DSM-IV criteria) and 37 healthy controls were examined with the Liebowitz Social Anxiety Scale (LSAS) for social anxiety disorder and for the severity of social anxiety. The Positive and Negative Syndrome Scale (PANSS) and the Chapman scales for physical and social anhedonia were also administered. Data were collected from 2005 to 2010 from inpatient and outpatient research centers at the New York State Psychiatric Institute, New York. RESULTS: Social anxiety disorder was elevated more than 10-fold in schizophrenia patients than in controls (37.7% of patients vs 2.9% of controls, P <= .001). Social anxiety and social fear were unrelated to the PANSS with few exceptions. A family history of psychosis was also a significant independent predictor of social anxiety as measured by LSAS total (P = .004) and the social fear subscale (P = .007). CONCLUSIONS: These data confirm social anxiety disorder as a prominent comorbid disorder in patients with schizophrenia. Future studies should focus on treatment trials of this phenomenon. Social anxiety cannot be explained by the negative symptomatology of the disease. This study suggests that a family history of psychosis is a significant predictor of social anxiety. PMID- 26835175 TI - Attempted Suicide Among Students and Young Adults in Montreal, Quebec, Canada: A Retrospective Cross-Sectional Study of Hospitalized and Nonhospitalized Suicide Attempts Based on Chart Review. AB - OBJECTIVE: We conducted a chart review to identify postsecondary students and nonstudents in the same age range who presented to the emergency department following a suicide attempt to (1) compare demographic characteristics and suicide risk factors and (2) determine factors associated with more serious attempts requiring hospitalizations. METHOD: The study was conducted in 1 tertiary trauma hospital and 1 community hospital affiliated with McGill University, Montreal, Quebec, Canada, between January 1, 2009, and March 31, 2010. Charts of patients with potential suicide attempts were identified from medical records using ICD-10 codes that indicated traumatic injury, intentional self-harm, poisoning, and psychiatric or perception/cognition disorders and from the emergency department triage file using keywords that indicated suicidality or self-harm at presentation. RESULTS: In multivariable logistic regression models (odds ratio, 95% CI), students were younger (per 5-year increase: 0.22, 0.12 0.41), less likely to be born in Canada (0.17, 0.06-0.44), and more likely to use less violent methods (laceration, poisoning, other, multiple methods) versus more violent methods (collision, jump, fire burns, firearm, hanging) in their attempt. Fewer students had a history of substance abuse (0.12, 0.02-0.94) but were not different from nonstudents on history of other mental disorders. Less students attempted suicide in the winter/spring (January-April) versus fall (September December) semester (0.32, 0.11-0.91). Students who attempted suicide were more likely to have family/social support. Those who attempted suicide in the previous year were more likely to require hospitalization for their current suicide attempt. CONCLUSIONS: Knowledge of specific factors associated with suicide attempts in young people can help inform and guide suicide prevention efforts in both academic and community settings. Specific to the findings of this study regarding the method of suicide attempt used, for example, limiting access to dangerous substances or large quantities of medications may help prevent or reduce suicide attempts in this population. PMID- 26835176 TI - Medication Use and Metabolic Syndrome Among Overweight/Obese Patients With and Without Binge-Eating Disorder in a Primary Care Sample. AB - OBJECTIVE: To examine metabolic factors among overweight/obese individuals with binge-eating disorder (BED) and non-binge-eating overweight/obese (NBO) patients recruited from primary care and to examine and compare medication use by these groups. METHOD: Participants were 102 adults recruited for a weight loss study within primary care centers who were assessed for BED (28 [38%] met DSM-5 BED criteria). Participants completed a medication log, had physiologic measurements taken, and were evaluated for the presence of metabolic syndrome using 2 methods. Data were collected between February 2012 and October 2012. RESULTS: The BED group had a higher mean body mass index (BMI), a higher pulse, and a larger waist circumference than the NBO group. Of the sample, 65% reported current medication use (prescription and/or over-the-counter medications): 19.6% took 3 to 4 medications and 15.7% took >= 5 medications. Aside from vitamin and over-the counter allergy pill use, there were no differences in medication use between BED and NBO patients. Full metabolic syndrome (>= 3 criteria met) was present in 31.5% of the sample when using objective measurement alone, and 39.1% of the sample when defined by objective measurement and pharmacologic management. No significant differences were observed regardless of definition. CONCLUSIONS: Despite higher BMI, pulse, and waist circumference, the current sample of BED patients in primary care did not present with poorer metabolic health than NBO patients. PMID- 26835177 TI - Long-Term Neurodevelopmental Outcomes in Children and Adolescents With Congenital Heart Disease. AB - BACKGROUND: Effective medical and surgical management of pediatric congenital heart disease (CHD) to reduce long-term adverse neurodevelopmental outcomes is an important clinical objective in primary and specialty health care. We identify clinical predictors associated with an increased risk of 6 long-term neurodevelopmental outcomes in children with CHD compared to the general pediatric Medicaid population. METHOD: South Carolina's retrospective, 15-year Medicaid data set (January 1, 1996-December 31, 2010) for 19,947 patients aged <= 17 years diagnosed with >= 1 CHD lesions (on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification codes) were compared to 19,948 patients without CHD matched on age at entry into and duration in Medicaid using logistic and Cox proportional hazards regression. RESULTS: The CHD cohort was significantly less likely to have incident neurologic or psychiatric disorders, mental retardation, developmental delays, or inattention/hyperactivity (adjusted odds ratios [ORs] = 0.34, 0.56, 0.03, 0.01, 0.004, respectively) but was more likely to have incident seizures (OR = 2.00) compared to controls. Exposure to both cardiac and noncardiac surgical intervention was associated with a significantly increased risk of developing neurologic or psychiatric disorders, mental retardation, developmental delays, or inattention/hyperactivity (cardiac ORs = 1.66, 2.00, 1.67, 1.43, 1.76, respectively) (noncardiac ORs = 2.25, 1.59, 1.48, 1.29, 1.36, 2.46, respectively). Any documented hypoxemia was associated with a significantly increased risk of developing 5 of the neurodevelopmental conditions (neurologic OR = 4.52, psychiatric OR = 1.60, mental retardation OR = 2.90, developmental delay OR = 2.12, seizures OR = 4.23). CONCLUSION: Practitioners should maintain vigilant surveillance of all CHD patients, especially those exposed to surgical procedures or experiencing hypoxemia, to identify any neurodevelopmental issues early and address them promptly. PMID- 26835179 TI - Integrating a Patient Safety Conference into Graduate Medical Education. AB - OBJECTIVES: The Institute of Medicine has established aims for improvement in patient care that emphasize safe, timely, effective, efficient, equitable, and patient-centered medicine. This goal is echoed by the Accreditation Council for Graduate Medical Education (ACGME). METHODS: The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) graduate medical education program implemented a Clinical Learning Environment Review (CLER) project whose aim is to support a patient and trainee safety environment. An ongoing biannual patient and learner safety conference is able to capture close calls, safety attitudes, potential learner mistreatment, and trainee fatigue in a nonpunitive manner that supports answering the question, "What was learned and what needs to be improved?" RESULTS: Group recommendations were captured at a quality improvement conference. We documented a shift in attitudes away from one where the institution is perceived to be weakest at supporting safety reporting. CONCLUSIONS: This project is designed to serve as a mechanism for insuring care that is respectful and responsive to patient needs and values. It identifies keys to avoiding wasted re-sources or harmful delay while also seeking to improve care based upon scientific knowledge. PMID- 26835180 TI - Virtual Averaging Making Nonframe-Averaged Optical Coherence Tomography Images Comparable to Frame-Averaged Images. AB - PURPOSE: Developing a novel image enhancement method so that nonframe-averaged optical coherence tomography (OCT) images become comparable to active eye tracking frame-averaged OCT images. METHODS: Twenty-one eyes of 21 healthy volunteers were scanned with noneye-tracking nonframe-averaged OCT device and active eye-tracking frame-averaged OCT device. Virtual averaging was applied to nonframe-averaged images with voxel resampling and adding amplitude deviation with 15-time repetitions. Signal-to-noise (SNR), contrast-to-noise ratios (CNR), and the distance between the end of visible nasal retinal nerve fiber layer (RNFL) and the foveola were assessed to evaluate the image enhancement effect and retinal layer visibility. Retinal thicknesses before and after processing were also measured. RESULTS: All virtual-averaged nonframe-averaged images showed notable improvement and clear resemblance to active eye-tracking frame-averaged images. Signal-to-noise and CNR were significantly improved (SNR: 30.5 vs. 47.6 dB, CNR: 4.4 vs. 6.4 dB, original versus processed, P < 0.0001, paired t-test). The distance between the end of visible nasal RNFL and the foveola was significantly different before (681.4 vs. 446.5 MUm, Cirrus versus Spectralis, P < 0.0001) but not after processing (442.9 vs. 446.5 MUm, P = 0.76). Sectoral macular total retinal and circumpapillary RNFL thicknesses showed systematic differences between Cirrus and Spectralis that became not significant after processing. CONCLUSION: The virtual averaging method successfully improved nontracking nonframe-averaged OCT image quality and made the images comparable to active eye-tracking frame-averaged OCT images. TRANSLATIONAL RELEVANCE: Virtual averaging may enable detailed retinal structure studies on images acquired using a mixture of nonframe-averaged and frame-averaged OCT devices without concerning about systematic differences in both qualitative and quantitative aspects. PMID- 26835178 TI - Gabapentin Therapy in Psychiatric Disorders: A Systematic Review. AB - OBJECTIVE: Gabapentin is commonly used off-label in the treatment of psychiatric disorders with success, failure, and controversy. A systematic review of the literature was performed to elucidate the evidence for clinical benefit of gabapentin in psychiatric disorders. DATA SOURCES: Bibliographic reference searches for gabapentin use in psychiatric disorders were performed in PubMed and Ovid MEDLINE search engines with no language restrictions from January 1, 1983, to October 1, 2014, excluding nonhuman studies. For psychiatric references, the keywords bipolar, depression, anxiety, mood, posttraumatic stress disorder (posttraumatic stress disorder and PTSD), obsessive-compulsive disorder (obsessive-compulsive disorder and OCD), alcohol (abuse, dependence, withdraw), drug (abuse, dependence, withdraw), opioid (abuse, dependence, withdraw), cocaine (abuse, dependence, withdraw), and amphetamine (abuse, dependence, withdraw) were crossed with gabapentin OR neurontin. STUDY SELECTION AND DATA EXTRACTION: The resulting 988 abstracts were read by 2 reviewers; references were excluded if gabapentin was not a study compound or psychiatric symptoms were not studied. The resulting references were subsequently read, reviewed, and analyzed; 219 pertinent to gabapentin use in psychiatric disorders were retained. Only 34 clinical trials investigating psychiatric disorders contained quality of evidence level II-2 or higher. RESULTS: Gabapentin may have benefit for some anxiety disorders, although there are no studies for generalized anxiety disorder. Gabapentin has less likely benefit adjunctively for bipolar disorder. Gabapentin has clearer efficacy for alcohol craving and withdrawal symptoms and may have a role in adjunctive treatment of opioid dependence. There is no clear evidence for gabapentin therapy in depression, PTSD prevention, OCD, or other types of substance abuse. Limitations of available data include variation in dosing between studies, gabapentin as monotherapy or adjunctive treatment, and differing primary outcomes between trials. CONCLUSIONS: Further research is required to better clarify the benefit of gabapentin in psychiatric disorders. PMID- 26835181 TI - Computer-Assisted Diabetes Risk Assessment and Education (CADRAE) for Medically Vulnerable Populations in the Middle East: a Novel and Practical Method for Prevention. AB - The prevalence of diabetes in the Middle East is increasing rapidly due to urbanization, reduced levels of physical activity, and a nutritional transition toward increased consumption of fats and refined carbohydrates. Preventive strategies are of paramount importance to stemming the tide. Portable touch screen computer technology may hold an answer for alleviating the burdens of cost, time, and training that limit the implementation of diabetes risk screening and intervention, especially among refugees and other vulnerable populations. The Computer-Assisted Diabetes Risk Assessment and Education (CADRAE) Arabic-language intervention program is proposed as a model method for practicing proactive type 2 diabetes prevention in resource-limited settings of the Middle East that combines the efficiency of risk-score screening methods, the advantages of portable computer interface, and the spirit of brief motivational interviewing. This paper aims to describe the theory and novel design of CADRAE-introduced at the Noor Al Hussein Foundation's Institute of Family Health in January 2014-as well as discuss opportunities and challenges for its implementation and evaluation in primary or emergency care settings. Features of CADRAE are elucidated in detail, including development, translation, conceptual framework, theoretical basis, method of risk assessment, brief intervention style, definition of outcomes, requirements for implementation, and potential means of evaluation and quality improvement. CADRAE offers the first example of portable computer technology integrating diabetes risk screening with behavior change counseling tailored for an Arabic-speaking population of mostly refugees and could offer a valuable model for researchers and policy makers of the Middle East as well as other resource-limited settings. PMID- 26835182 TI - The Risk for Cardiovascular Events Associated with Hyperlipdemia among Patients with and Without Rheumatoid Arthritis. AB - OBJECTIVES: To determine, using data from a real-world setting, the overall and sex-specific risk of cardiovascular (CV) events in patients with rheumatoid arthritis (RA), with or without comorbid hyperlipidemia, relative to those in a non-RA cohort. METHODS: This retrospective cohort study using claims data from a US commercial health plan (2005-2011) included patients with RA and a matched non RA cohort. Cox proportional hazards regression model determined the hazard ratio (HR) for CV events (myocardial infarction, stroke, revascularization procedures), using the presence of RA and hyperlipidemia as the independent variables, controlling for other covariates (age, sex, diabetes, and hypertension). RESULTS: The incidence of CV events per 1000 person-years was 10.19 for the RA cohort and 6.41 for the non-RA cohort (crude rate ratio [RR] =1.59). Within the RA cohort, incidence was 15.54 for patients with hyperlipidemia and 7.05 for patients without hyperlipidemia (crude RR=2.21); in the non-RA cohort, incidence was 10.55 and 3.82 for those with and without hyperlipidemia, respectively (crude RR=2.76). After controlling for covariates, the HR of CV events among RA patients was 1.68 (95% CI: 1.50, 1.87) relative to non-RA patients. After multivariable adjustment, hyperlipidemia conferred a significant risk of CV events in both RA and non-RA patients; the interaction between RA and hyperlipidemia was not significant (p=0.13). CONCLUSION: This real-world analysis demonstrates that patients with RA have an increased risk of CV events. Similar to a non-RA cohort, CV event rates were incrementally higher for those patients with hyperlipidemia. SIGNIFICANCE: Cardiovascular disease is an increasingly visible topic of concern in the rheumatoid arthritis community. However, there are only limited data that informs both the absolute and relative rates of CVD events, and the contribution of various risk factors such as hyperlipidemia, compared to non-RA populationsThe 'lipid paradox' hypothesis in RA suggests that elevated LDL cholesterol has a negligible effect on CVD risk in RA, unlikely in the general population where it is a well-accepted CVD risk factorThe incidence of CVD events in RA patients was 10/1000 patient years, a 1.6 fold greater risk compared to non-RA patientsThe contribution of hyperlipidemia to CVD risk was associated with comparable or greater absolute increases in the rate of CV events compared to non RA patients, a finding that does not support the lipid paradox. PMID- 26835183 TI - A new species of Metopocetus (Cetacea, Mysticeti, Cetotheriidae) from the Late Miocene of the Netherlands. AB - The family Cetotheriidae has played a major role in recent discussions of baleen whale phylogenetics. Within this group, the enigmatic, monotypic Metopocetus durinasus has been interpreted as transitional between herpetocetines and other members of the family, but so far has been restricted to a single, fragmentary cranium of uncertain provenance and age. Here, we expand the genus and shed new light on its phylogenetic affinities and functional morphology by describing Metopocetus hunteri sp. nov. from the Late Miocene of the Netherlands. Unlike the holotype of M. durinasus, the material described here is confidently dated and preserves both the tympanic bulla and additional details of the basicranium. M. hunteri closely resembles M. durinasus, differing primarily in its somewhat less distally expanded compound posterior process of the tympanoperiotic. Both species are characterised by the development of an unusually large fossa on the ventral surface of the paroccipital process, which extends anteriorly on to the compound posterior process and completely floors the facial sulcus. In life, this enlarged fossa may have housed the posterior sinus and/or the articulation of the stylohyal. Like other cetotheriids, Metopocetus also bears a well-developed, posteriorly-pointing dorsal infraorbital foramen near the base of the ascending process of the maxilla, the precise function of which remains unclear. PMID- 26835184 TI - Generating optimal control simulations of musculoskeletal movement using OpenSim and MATLAB. AB - Computer modeling, simulation and optimization are powerful tools that have seen increased use in biomechanics research. Dynamic optimizations can be categorized as either data-tracking or predictive problems. The data-tracking approach has been used extensively to address human movement problems of clinical relevance. The predictive approach also holds great promise, but has seen limited use in clinical applications. Enhanced software tools would facilitate the application of predictive musculoskeletal simulations to clinically-relevant research. The open-source software OpenSim provides tools for generating tracking simulations but not predictive simulations. However, OpenSim includes an extensive application programming interface that permits extending its capabilities with scripting languages such as MATLAB. In the work presented here, we combine the computational tools provided by MATLAB with the musculoskeletal modeling capabilities of OpenSim to create a framework for generating predictive simulations of musculoskeletal movement based on direct collocation optimal control techniques. In many cases, the direct collocation approach can be used to solve optimal control problems considerably faster than traditional shooting methods. Cyclical and discrete movement problems were solved using a simple 1 degree of freedom musculoskeletal model and a model of the human lower limb, respectively. The problems could be solved in reasonable amounts of time (several seconds to 1-2 hours) using the open-source IPOPT solver. The problems could also be solved using the fmincon solver that is included with MATLAB, but the computation times were excessively long for all but the smallest of problems. The performance advantage for IPOPT was derived primarily by exploiting sparsity in the constraints Jacobian. The framework presented here provides a powerful and flexible approach for generating optimal control simulations of musculoskeletal movement using OpenSim and MATLAB. This should allow researchers to more readily use predictive simulation as a tool to address clinical conditions that limit human mobility. PMID- 26835185 TI - Decadal comparison of a diminishing coral community: a study using demographics to advance inferences of community status. AB - The most common coral monitoring methods estimate coral abundance as percent cover, either via in situ observations or derived from images. In recent years, growing interest and effort has focused on colony-based (demographic) data to assess the status of coral populations and communities. In this study, we relied on two separate data sets (photo-derived percent cover estimates, 2002-12, and opportunistic in situ demographic sampling, 2004 and 2012) to more fully infer decadal changes in coral communities at a small, uninhabited Caribbean island. Photo-derived percent cover documented drastic declines in coral abundance including disproportionate declines in Orbicella spp. While overall in situ estimates of total coral density were not different between years, densities of several rarer taxa were. Meandrina meandrites and Stephanocoenia intersepta increased while Leptoseris cucullata decreased significantly, changes that were not discernable from the photo-derived cover estimates. Demographic data also showed significant shifts to larger colony sizes (both increased mean colony sizes and increased negative skewness of size frequency distributions, but similar maximum colony sizes) for most taxa likely indicating reduced recruitment. Orbicella spp. differed from this general pattern, significantly shifting to smaller colony sizes due to partial mortality. Both approaches detected significant decadal changes in coral community structure at Navassa, though the demographic sampling provided better resolution of more subtle, taxon specific changes. PMID- 26835186 TI - Phylogeography of Arabidopsis halleri (Brassicaceae) in mountain regions of Central Europe inferred from cpDNA variation and ecological niche modelling. AB - The present study aimed to investigate phylogeographical patterns present within A. halleri in Central Europe. 1,281 accessions sampled from 52 populations within the investigated area were used in the study of genetic variation based on chloroplast DNA. Over 500 high-quality species occurrence records were used in ecological niche modelling experiments. We evidenced the presence of a clear phylogeographic structure within A. halleri in Central Europe. Our results showed that two genetically different groups of populations are present in western and eastern part of the Carpathians. The hypothesis of the existence of a glacial refugium in the Western Carpathians adn the Bohemian Forest cannot be rejected from our data. It seems, however, that the evidence collected during the present study is not conclusive. The area of Sudetes was colonised after LGM probably by migrants from the Bohemian Forest. PMID- 26835187 TI - Deficiencies of effectiveness of intervention studies in veterinary medicine: a cross-sectional survey of ten leading veterinary and medical journals. AB - The validity of studies that assess the effectiveness of an intervention (EoI) depends on variables such as the type of study design, the quality of their methodology, and the participants enrolled. Five leading veterinary journals and 5 leading human medical journals were hand-searched for EoI studies for the year 2013. We assessed (1) the prevalence of randomized controlled trials (RCTs) among EoI studies, (2) the type of participants enrolled, and (3) the methodological quality of the selected studies. Of 1707 eligible articles, 590 were EoI articles and 435 RCTs. Random allocation to the intervention was performed in 52% (114/219; 95%CI:45.2-58.8%) of veterinary EoI articles, against 87% (321/371; 82.5-89.7%) of human EoI articles (adjusted OR:9.2; 3.4-24.8). Veterinary RCTs were smaller (median: 26 animals versus 465 humans) and less likely to enroll real patients, compared with human RCTs (OR:331; 45-2441). Only 2% of the veterinary RCTs, versus 77% of the human RCTs, reported power calculations, primary outcomes, random sequence generation, allocation concealment and estimation methods. Currently, internal and external validity of veterinary EoI studies is limited compared to human medical ones. To address these issues, veterinary interventional research needs to improve its methodology, increase the number of published RCTs and enroll real clinical patients. PMID- 26835188 TI - An analysis of structural relationship among achievement motive on social participation, purpose in life, and role expectations among community dwelling elderly attending day services. AB - Background. Achievement motive is defined as the intention to achieve one's goals. Achievement motive is assumed to promote clients to choices and actions toward their valuable goal, so it is an important consideration in rehabilitation. Purpose. The purpose of this study is to demonstrate the structural relationship among achievement motive on purpose in life, social participation, and role expectation of community-dwelling elderly people. Methods. Participants were community-dwelling elderly people in day-service centers. A total of 281 participants (male: 127, female: 154) answered the self administered questionnaire in cross-sectional research. The questionnaire was comprised of demographic data and scales that evaluated achievement motive, social participation, purpose in life, and role expectation. We studied the structural relationship established by our hypothesized model via a structural equation modeling approach. Results. We checked the standardized path coefficients and the modification indices; the modified model's statistics were a good fit: CFI = 0.984, TLI = 0.983, RMSEA = 0.050, 90% CI [0.044-0.055]. Achievement motive had a significantly direct effect on purpose in life (direct effect = 0.445, p value < 0.001), a significantly indirect effect on purpose in life via social participation or role expectation (indirect effect = 0.170, p value < 0.001) and a total effect on purpose in life (total effect = 0.615). Discussion. This result suggests that enhancing the intention to achieve one's goals enables participants to feel a spirit of challenge with a purpose and a sense of fulfillment in their daily lives. PMID- 26835189 TI - AMAS: a fast tool for alignment manipulation and computing of summary statistics. AB - The amount of data used in phylogenetics has grown explosively in the recent years and many phylogenies are inferred with hundreds or even thousands of loci and many taxa. These modern phylogenomic studies often entail separate analyses of each of the loci in addition to multiple analyses of subsets of genes or concatenated sequences. Computationally efficient tools for handling and computing properties of thousands of single-locus or large concatenated alignments are needed. Here I present AMAS (Alignment Manipulation And Summary), a tool that can be used either as a stand-alone command-line utility or as a Python package. AMAS works on amino acid and nucleotide alignments and combines capabilities of sequence manipulation with a function that calculates basic statistics. The manipulation functions include conversions among popular formats, concatenation, extracting sites and splitting according to a pre-defined partitioning scheme, creation of replicate data sets, and removal of taxa. The statistics calculated include the number of taxa, alignment length, total count of matrix cells, overall number of undetermined characters, percent of missing data, AT and GC contents (for DNA alignments), count and proportion of variable sites, count and proportion of parsimony informative sites, and counts of all characters relevant for a nucleotide or amino acid alphabet. AMAS is particularly suitable for very large alignments with hundreds of taxa and thousands of loci. It is computationally efficient, utilizes parallel processing, and performs better at concatenation than other popular tools. AMAS is a Python 3 program that relies solely on Python's core modules and needs no additional dependencies. AMAS source code and manual can be downloaded from http://github.com/marekborowiec/AMAS/ under GNU General Public License. PMID- 26835190 TI - Stage IV EGFR Mutation-Negative and ALK Mutation-Negative Lung Adenocarcinoma: Long-Term Survival is Possible. AB - Lung cancer is the leading cause of cancer death in the United States with a five year survival of 16.8% for all stages and median survival of four months for Stage IV disease. We report a case of a 54-year-old male with a seven-year survival after being diagnosed with Stage IV epidermal growth factor receptor (EGFR) mutation-negative and anaplastic lymphoma kinase (ALK) mutation-negative adenocarcinoma of the lung, demonstrating an exceptional response to treatment. PMID- 26835191 TI - Tumor Biology: Is It Time to Redefine Unresectability? An Extraordinary Case of Gastroesophageal Junctional Adenocarcinoma. AB - BACKGROUND: Disease assessment based on measurements of size and anatomic involvement have historically been central to surgical strategy. We propose this to be an outdated concept, which should be replaced by a deeper understanding of tumor biology and careful treatment planning. Report of case: A 34-year-old male was diagnosed with a Siewert Type 3 locally advanced cancer of the gastroesophageal junction, involving the coeliac axis and the superior mesenteric artery (SMA). He was treated with neoadjuvant chemotherapy, followed by chemoradiation, and then proceeded to surgery, at which time the tumor was judged unresectable. After extensive planning, a further surgery was attempted - an extended gastrectomy with distal esophagectomy, left hepatectomy, and splenectomy were performed. Additionally, the coeliac axis and the SMA were excised, followed by reconstruction of the hepatic artery and the SMA with grafts. Adjuvant chemotherapy was administered, and the patient is recurrence-free after five years follow-up. CONCLUSION: This case highlights the importance of the distinction between resectability and operability, and that patient treatment should be tailored and individualised based on the response to treatment, comorbidities, and underlying tumor biology. PMID- 26835192 TI - Basaloid Squamous Cell Carcinoma of the Ethmoid Sinus with Invasion into the Skull Base Treated with Craniofacial Resection and Adjuvant Intensity-Modulated Radiation Therapy: A Case Report. AB - Basaloid squamous cell carcinoma (BSCC) is a rare variant of squamous cell carcinoma (SCC), which is highly aggressive, with a tendency for multifocality, local invasion, and with a high metastatic potential. Less than forty cases of BSCC of the sinonasal tract have been reported in the literature, and no reports were found on sinonasal BSCC arising from the ethmoid sinus. We report the case of a 78-year-old man who presented with BSCC arising from the ethmoid sinus with extensive bone destruction and intracranial extension. He was treated with craniofacial resection followed by adjuvant intensity-modulated radiation therapy to the tumor bed (60 Gy in 30 fractions), and the upper neck lymph nodes (50 Gy in 25 fractions). At the patient's last follow-up, four months after diagnosis, there was no evidence of disease. Aggressive management using craniofacial resection followed by adjuvant radiation therapy with or without radiosensitizing chemotherapy seems to be a reasonable approach to this challenging disease. PMID- 26835193 TI - Relationship of Hypertensive Retinopathy with Mean Platelet Volume Among Hypertensive Patients. AB - Background The pathophysiological mechanism of hypertensive retinopathy (HR) is not fully understood, although it is thought that increased platelet activation may have a pivotal role. This study was designed to investigate this possibility by determining the frequency and magnitude of mean platelet volume (MPV), a marker of platelet activation, in HR. Methods One hundred and thirty-eight patients, aged 31 to 80 years, who had essential hypertension with HR were enrolled in the study. The patients who presented at the emergency and outpatient medical department of the Capital Development Authority (CDA) Hospital, Islamabad, Pakistan, from March 2013 to February 2014 were selected for this study. All patients were analyzed for grading of HR according to the Keith Wagener-Barker (KWB) classification criteria. A direct ophthalmoscopic examination was performed in all the subjects, together with an assessment of MPV. Results The mean age of the patients was 54.1 +/- 11.7 years. Normal MPV was found in 97 (70.2%) patients, 53 males and 44 females. Elevated levels of MPV were found in 41 (29.7%) patients, 19 males and 22 females. In patients with Grade 1 HR, the MPV was 10.6 +/- 0.6 femtoliters (fl). In Grades 2, 3, and 4 HR, the values of MPV were 11.1+/- 0.5 fl, 11.6 +/- 0.3 fl, and 12.2 +/- 0.6 fl, respectively, which were greater than the normal range (> 10 fl) of MPV values. In addition, the frequency of elevated MPV significantly (P < 0.001) and linearly (r = 0.998) increased with increasing HR grade. Conclusion It is concluded that the frequency of elevated MPV is increased in patients with HR and strongly correlates to grade. In addition, the magnitude of the elevated MPV increased with the severity of the retinopathy. Thus, abnormally elevated MPV may be an etiological factor for HR in hypertensive patients. PMID- 26835194 TI - Changes for the Future. PMID- 26835195 TI - Lifestyle-Related Diseases Affect Surgical Outcomes after Posterior Lumbar Interbody Fusion. AB - Study Design Retrospective study. Objective Hyperlipidemia (HL) and hypertension (HT) lead to systemic atherosclerosis. Not only atherosclerosis but also bone fragility and/or low bone mineral density result from diabetes mellitus (DM) and chronic kidney disease (CKD). The purpose of this study was to examine whether these lifestyle-related diseases affected surgical outcomes after posterior lumbar interbody fusion (PLIF). Methods The subjects comprised 122 consecutive patients who underwent single-level PLIF for degenerative lumbar spinal disorders. The clinical results were assessed using the Japanese Orthopaedic Association (JOA) score before surgery and at 2 years postoperatively. The fusion status was graded as union in situ, collapsed union, or nonunion at 2 years after surgery. The abdominal aorta calcification (AAC) score was assessed using preoperative lateral radiographs of the lumbar spine. Results HL did not significantly affect the JOA score recovery rate. On the other hand, HT and CKD (stage 3 to 4) had a significant adverse effect on the recovery rate. The recovery rate was also lower in the DM group than in the non-DM group, but the difference was not significant. The AAC score was negatively correlated with the JOA score recovery rate. The fusion status was not significantly affected by HL, HT, DM, or CKD; however, the AAC score was significantly higher in the collapsed union and nonunion group than in the union in situ group. Conclusions At 2 years after PLIF, the presence of HT, CKD, and AAC was associated with significantly worse clinical outcomes, and advanced AAC significantly affected fusion status. PMID- 26835196 TI - Cervical Scoliosis: Clinical and Radiographic Outcomes. AB - Study Design Retrospective study. Objective Cervical scoliosis is a rare condition that can arise from various etiologies. Few reports on the surgical management of cervical scoliosis exist. Our objective was to evaluate clinical and radiographic outcomes following surgical management of cervical scoliosis. Methods We evaluated our cervical spine surgical database for patients with cervical scoliosis (Cobb angle > 10 degrees) from 2005 to 2010. Demographic data including age, gender, diagnoses, and primary versus revision surgery was collected. Surgical data including procedure (anterior versus posterior), estimated blood loss (EBL), length of surgery, length of hospitalization, and complications was recorded. Preoperative and postoperative Cobb angle measurements and Neck Disability Index (NDI) scores were recorded. Results Cervical scoliosis was identified in 18 patients. We excluded 5, leaving 5 men and 8 women with an average age of 50.7 (median 52, range 25 to 65). The average follow-up was 40 months (median 36.5, range 5 to 87). An anterior-only approach was used in 6 cases (average 4 levels fused), 5 cases were posterior-only approach (average 8.7 levels fused), and 2 cases were combined anterior-posterior approach. The EBL was an average of 286 mL (median 150, range 50 to 900), the average surgical time was 266 minutes (median 239, range 136 to 508), and the average hospital stay was 2.7 days (median 2, range 1 to 7). Complications occurred in 7 patients, and 2 developed adjacent segment pathology. The average coronal Cobb angle preoperatively was 35.1 degrees (median 31, range 13 to 63) and corrected was 15.7 degrees (median 10.5, range 2 to 59) postoperatively (p < 0.005). The average NDI preoperatively was 24.9 (median 26, range 6 to 37) and was reduced to 17.8 (median 18, range 7 to 30) postoperatively (p < 0.02). Conclusion Surgical management of cervical scoliosis can result in deformity correction and improvement in patient outcomes. Higher rates of complications may be encountered. PMID- 26835197 TI - Anterior Lumbar Interbody Fusion as a Salvage Technique for Pseudarthrosis following Posterior Lumbar Fusion Surgery. AB - Study Design Retrospective analysis of prospectively collected observational data. Objective To assess the safety and efficacy of anterior lumbar interbody fusion (ALIF) as a salvage option for lumbar pseudarthrosis following failed posterior lumbar fusion surgery. Methods From 2009 to 2013, patient outcome data was collected prospectively over 5 years from 327 patients undergoing ALIF performed by a single surgeon (R.J.M.) with 478 levels performed. Among these, there were 20 cases of failed prior posterior fusion that subsequently underwent ALIF. Visual analog score (VAS), Oswestry Disability Index (ODI), and Short Form 12-item health survey (SF-12) were measured pre- and postoperatively. The verification of fusion was determined by utilizing a fine-cut computed tomography scan at 12-month follow-up. Results There was a significant difference between the preoperative (7.25 +/- 0.8) and postoperative (3.1 +/- 2.1) VAS scores (p < 0.0001). The ODI scale also demonstrated a statistically significant reduction from preoperative (56.3 +/- 16.5) and postoperative (30.4 +/- 19.3) scores (p < 0.0001). The SF-12 scores were significantly improved after ALIF salvage surgery: Physical Health Composite Score (32.18 +/- 5.5 versus 41.07 +/- 9.67, p = 0.0003) and Mental Health Composite Score (36.62 +/- 12.25 versus 50.89 +/- 10.86, p = 0.0001). Overall, 19 patients (95%) achieved successful fusion. Conclusions Overall, our results suggest that the ALIF procedure results not only in radiographic improvements in bony fusion but in significant improvements in the patient's physical and mental experience of pain secondary to lumbar pseudarthrosis. Future multicenter registry studies and randomized controlled trials should be conducted to confirm the long-term benefit of ALIF as a salvage option for failed posterior lumbar fusion. PMID- 26835198 TI - Surgical Outcomes in Patients with High Spinal Instability Neoplasm Score Secondary to Spinal Giant Cell Tumors. AB - Study Design Retrospective review. Objective To describe the surgical outcomes in patients with high preoperative Spinal Instability Neoplastic Score (SINS) secondary to spinal giant cell tumors (GCT) and evaluate the impact of en bloc versus intralesional resection and preoperative embolization on postoperative outcomes. Methods A retrospective analysis was performed on 14 patients with GCTs of the spine who underwent surgical treatment prior to the use of denosumab. A univariate analysis was performed comparing the patient demographics, perioperative characteristics, and surgical outcomes between patients who underwent en bloc marginal (n = 6) compared with those who had intralesional (n = 8) resection. Results Six patients underwent en bloc resections and eight underwent intralesional resection. Preoperative embolization was performed in eight patients. All patients were alive at last follow-up, with a mean follow-up length of 43 months. Patients who underwent en bloc resection had longer average operative times (p = 0.0251), higher rates of early (p = 0.0182) and late (p = 0.0389) complications, and a higher rate of surgical revision (p = 0.0120). There was a 25% (2/8 patients) local recurrence rate for intralesional resection and a 0% (0/6 patients) local recurrence rate for en bloc resection (p = 0.0929). Conclusions Surgical excision of spinal GCTs causing significant instability, assessed by SINS, is associated with high intraoperative blood loss despite embolization and independent of resection method. En bloc resection requires a longer operative duration and is associated with a higher risk of complications when compared with intralesional resection. However, the increased morbidity associated with en bloc resection may be justified as it may minimize the risk of local recurrence. PMID- 26835199 TI - The Effect of an Educational Intervention Program on the Adoption of Low Back Pain Preventive Behaviors in Nurses: An Application of the Health Belief Model. AB - Study Design Randomized controlled trial. Objective The purpose of this study was to identify the effect of a theory-based educational intervention program on the level of knowledge and Health Belief Model (HBM) constructs among nurses in terms of the adoption of preventive behaviors. Methods This pretest/posttest quasi experimental study was conducted on 100 nurses who were recruited through the multistage sampling method. The nurses were randomly assigned to intervention and control groups. The participants were evaluated before and 3 months after the educational intervention. A multidimensional questionnaire was prepared based on the theoretical structures of the HBM to collect the data. Data analysis was performed using descriptive and inferential statistics. Results There was no significant difference in the mean values of HBM constructs prior to the intervention between the intervention and control groups. However, after the administration of the educational program, the mean scores of knowledge and HBM constructs significantly increased in the intervention group when compared with the control group (p < 0.0001). Conclusion The results of the current study revealed that the educational intervention based on the HBM was effective in improving the nurses' scores of knowledge and HBM constructs; therefore, theory based health educational strategies are suggested as an effective alternative to traditional educational interventions. PMID- 26835201 TI - The Effect of Polymethyl Methacrylate Augmentation on the Primary Stability of Cannulated Bone Screws in an Anterolateral Plate in Osteoporotic Vertebrae: A Human Cadaver Study. AB - Study Design Cohort study. Objective Expandable anterolateral plates facilitate the reduction of posttraumatic deformities of thoracolumbar spine injuries and are commonly used in cases of unstable injuries or compromised bone quality. In this in vitro study, the craniocaudal yield load of the osseous fixation of an anterior angular stable plate fixation system and the effect of polymethyl methacrylate (PMMA) screw augmentation on the primary stability of the screw-bone interface during kyphosis reduction was evaluated in 12 osteoporotic human thoracolumbar vertebrae. Methods The anterolateral stabilization device used for this study is comprised of two swiveling flanges and an expandable midsection. It facilitates the controlled reduction of kyphotic deformities in situ with a geared distractor. Single flanges were attached to 12 thoracolumbar vertebrae. Six specimens were augmented with PMMA by means of cannulated bone screws. The constructs were subjected to static, displacement-controlled craniocaudal loading to failure in a servohydraulic testing machine. Results The uncemented screws cut out at a mean 393 +/- 66 N, whereas the cemented screws showed significantly higher yield load of 966 +/- 166 N (p < 0.02). We detected no significant correlation between bone mineral density and yield load in this setting. Conclusion Our results indicate that PMMA augmentation is an effective method to increase two- to threefold the primary stability of the screw-bone interface of an anterolateral spine stabilization system in osteoporotic bone. We recommend it in cases of severely compromised bone quality to reduce the risk of screw loosening during initial kyphosis correction and to increase long-term construct stability. PMID- 26835200 TI - An International Multicenter Study Assessing the Role of Ethnicity on Variation of Lumbar Facet Joint Orientation and the Occurrence of Degenerative Spondylolisthesis in Asia Pacific: A Study from the AOSpine Asia Pacific Research Collaboration Consortium. AB - Study Design A multinational, multiethnic, cross-sectional image-based study was performed in 33 institutions, representing 10 countries, which were part of the AOSpine Asia Pacific Research Collaboration Consortium. Objective Lumbar facet joint orientation has been reported to be associated with the development of degenerative spondylolisthesis (DS). The role of ethnicity regarding facet joint orientation remains uncertain. As such, the following study was performed across a wide-ranging population base to assess the role of ethnicity in facet joint orientation in patients with DS in the Asia Pacific region. Methods Lateral standing X-rays and axial magnetic resonance imaging scans were obtained for patients with lumbar DS. The DS parameters and facet joint angulations were assessed from L3-S1. Sex, age, body mass index (BMI), and ethnicity were also noted. Results The study included 371 patients with known ethnic origin (mean age: 62.0 years; 64% males, 36% females). The mean BMI was 25.6 kg/m(2). The level of DS was most prevalent at L4-L5 (74.7%). There were 28.8% Indian, 28.6% Japanese, 18.1% Chinese, 8.6% Korean, 6.5% Thai, 4.9% Caucasian, 2.7% Filipino, and 1.9% Malay patients. Variations in facet joint angulations were noted from L3 to S1 and between patients with and without DS (p < 0.05). No differences were noted with regards to sex and overall BMI to facet joint angulations (p > 0.05); however, increasing age was found to increase the degree of angulation throughout the lumbar spine (p < 0.05). Accounting for age and the presence or absence of DS at each level, no statistically significant differences between ethnicity and degree of facet joint angulations from L3-L5 were noted (p > 0.05). Ethnic variations were noted in non-DS L5-S1 facet joint angulations, predominantly between Caucasian, Chinese, and Indian ethnicities (p < 0.05). Conclusions This study is the first to suggest that ethnicity may not play a role in facet joint orientation in the majority of cases of DS in the Asia-Pacific region. Findings from this study may facilitate future comparative studies in other multiethnic populations. An understanding of ethnic variability may assist in identifying those patients at risk of postsurgical development or progression of DS. This study also serves as a model for large-scale multicenter studies across different ethnic groups and cultural boundaries in Asia. PMID- 26835202 TI - Incidence and Risk Factors for Late Neurologic Deterioration after C3-C6 Laminoplasty for Cervical Spondylotic Myelopathy. AB - Study Design Retrospective study. Objective We previously reported that the long term neurologic outcomes of C3-C6 laminoplasty for cervical spondylotic myelopathy (CSM) are satisfactory, with reduced frequencies of postoperative axial neck pain and kyphotic deformity. However, only 20 patients were included, which is a limitation in that study. The present study investigated the incidence of late neurologic deterioration (LND) of myelopathic symptoms after C3-C6 laminoplasty for CSM and attempted to identify significant risk factors for LND in a larger patient population. Methods Subjects comprised 137 consecutive patients with CSM who underwent C3-C6 laminoplasty (bilateral open-door laminoplasty, n = 85; unilateral open-door laminoplasty, n = 52) and were followed for >24 months (mean follow-up, 70 months; range, 25 to 124 months). The patients' medical records were examined for evidence of LND due to cervical myelopathy. The age at time of surgery, sex, surgical procedures, anteroposterior spinal canal diameter at the C7 level, type of C6 spinous process, pre- and postoperative C2-C7 angle, C3-C6 range of motion (ROM), and disk height at the C6 C7 level were analyzed to identify risk factors for LND. Results Three patients (2.2%) developed LND of myelopathic symptoms due to caudal segment pathology adjacent to the C3-C6 laminoplasty (LND group). In these three patients, mean Japanese Orthopaedic Association (JOA) score improved from 10.2 before surgery to 12.2 at the time of maximum recovery, and declined to 9.7 just before additional surgery. On the other hand, in 134 patients without LND (non-LND group), the mean JOA score significantly improved from 10.2 before surgery to 13.4 at the time of maximum recovery and was maintained by the final follow-up (13.2). Compared with the non-LND group, the LND group showed significantly smaller anteroposterior spinal canal diameter at C7, more restricted postoperative C3-C6 ROM, and greater postoperative decrease in disk height at C6-C7, although a logistic regression analysis showed no significant differences. Conclusions In patients with CSM with more severe developmental spinal canal stenosis at C7, accelerated degeneration at the caudal segment resulting from restricted C3-C6 ROM after C3-C6 laminoplasty might lead to LND. PMID- 26835203 TI - Ovariectomy-Induced Osteoporosis Does Not Impact Fusion Rates in a Recombinant Human Bone Morphogenetic Protein-2-Dependent Rat Posterolateral Arthrodesis Model. AB - Study Design Randomized, controlled animal study. Objective Recombinant human bone morphogenetic protein-2 (rhBMP-2) is frequently utilized as a bone graft substitute in spinal fusions to overcome the difficult healing environment in patients with osteoporosis. However, the effects of estrogen deficiency and poor bone quality on rhBMP-2 efficacy are unknown. This study sought to determine whether rhBMP-2-induced healing is affected by estrogen deficiency and poor bone quality in a stringent osteoporotic posterolateral spinal fusion model. Methods Aged female Sprague-Dawley rats underwent an ovariectomy (OVX group) or a sham procedure, and the OVX animals were fed a low-calcium, low-phytoestrogen diet. After 12 weeks, the animals underwent a posterolateral spinal fusion with 1 MUg rhBMP-2 on an absorbable collagen sponge. Representative animals were sacrificed at 1 week postoperative for alkaline phosphatase (ALP) and osteocalcin serum analyses. The remaining animals underwent radiographs 2 and 4 weeks after surgery and were subsequently euthanized for fusion analysis by manual palpation, micro computed tomography (CT) imaging, and histologic analysis. Results The ALP and osteocalcin levels were similar between the control and OVX groups. Manual palpation revealed no significant differences in the fusion scores between the control (1.42 +/- 0.50) and OVX groups (1.83 +/- 0.36; p = 0.07). Fusion rates were 100% in both groups. Micro-CT imaging revealed no significant difference in the quantity of new bone formation, and histologic analysis demonstrated bridging bone across the transverse processes in fused animals from both groups. Conclusions This study demonstrates that estrogen deficiency and compromised bone quality do not negatively influence spinal fusion when utilizing rhBMP-2, and the osteoinductive capacity of the growth factor is not functionally reduced under osteoporotic conditions in the rat. Although osteoporosis is a risk factor for pseudarthrosis/nonunion, rhBMP-2-induced healing was not inhibited in osteoporotic rats. PMID- 26835204 TI - The 100 Most Influential Articles in Cervical Spine Surgery. AB - Study Design Literature review. Objective To identify and analyze the top 100 cited articles in cervical spine surgery. Methods The Thomson Reuters Web of Knowledge was searched for citations of all articles relevant to cervical spine surgery. The number of citations, authorship, year of publication, journal of publication, country of publication, and institution were recorded for each article. Results The most cited article was the classic from 1991 by Vernon and Mior that described the Neck Disability Index. The second most cited was Smith's 1958 article describing the anterior cervical diskectomy and fusion procedure. The third most cited article was Hilibrand's 1999 publication evaluating the incidence, prevalence, and radiographic progression of symptomatic adjacent segment disease following anterior cervical arthrodesis. The majority of the articles originated in the United States (65), and most were published in Spine (39). Most articles were published in the 1990s (34), and the three most common topics were cervical fusion (17), surgical complications (9), and biomechanics (9), respectively. Author Abumi had four articles in the top 100 list, and authors Goffin, Panjabi, and Hadley had three each. The Department of Orthopaedic Surgery at Hokkaido University in Sapporo, Japan, had five articles in the top 100 list. Conclusion This report identifies the top 100 articles in cervical spine surgery and acknowledges those individuals who have contributed the most to the advancement of the study of the cervical spine and the body of knowledge used to guide evidence-based clinical decision making in cervical spine surgery today. PMID- 26835205 TI - Thoracolumbar Injury Classification and Injury Severity Score System: A Literature Review of Its Safety. AB - Study Design Systematic literature review. Objective The Thoracolumbar Injury Classification and Severity Score System (TLICS) is widely used to help guide the treatment of thoracolumbar spine trauma. The purpose of this study is to evaluate the safety of the TLICS in clinical practice. Methods Using the Medline database without time restriction, we performed a systematic review using the keyword "Thoracolumbar Injury Classification," searching for articles utilizing the TLICS. We classified the results according to their level of evidence and main conclusions. Results Nine articles met our inclusion and exclusion criteria. One article evaluated the safety of the TLICS based on its clinical application (level II). The eight remaining articles were based on retrospective application of the score, comparing the proposed treatment suggested by the TLICS with the treatment patients actually received (level III). The TLICS was safe in surgical and nonsurgical treatment with regards to neurologic status. Some studies reported that the retrospective application of the TLICS had inconsistencies with the treatment of burst fractures without neurologic deficits. Conclusions This literature review suggested that the TLICS use was safe especially with regards to preservation or improvement of neurologic function. Further well-designed multicenter prospective studies of the TLICS application in the decision making process would improve the evidence of its safety. Special attention to the TLICS application in the treatment of stable burst fractures is necessary. PMID- 26835208 TI - EBSJ Evidence Assessment. PMID- 26835206 TI - Success in Spine Care: The Proof Is in the Measurements, Part III. PMID- 26835207 TI - Return to Play in Athletes Receiving Cervical Surgery: A Systematic Review. AB - Study Design Systematic review. Clinical Questions Among athletes who undergo surgery of the cervical spine, (1) What proportion return to play (RTP) after their cervical surgery? (2) Does the proportion of those cleared for RTP depend on the type of surgical procedure (artificial disk replacement, fusion, nonfusion foraminotomies/laminoplasties), number of levels (1, 2, or more levels), or type of sport? (3) Among those who return to their presurgery sport, how long do they continue to play? (4) Among those who return to their presurgery sport, how does their postoperative performance compare with their preoperative performance? Objectives To evaluate the extent and quality of published literature on the topic of return to competitive athletic completion after cervical spinal surgery. Methods Electronic databases and reference lists of key articles published up to August 19, 2015, were searched to identify studies reporting the proportion of athletes who RTP after cervical spine surgery. Results Nine observational, retrospective series consisting of 175 patients were included. Seven reported on professional athletes and two on recreational athletes. Seventy-five percent (76/102) of professional athletes returned to their respective sport following surgery for mostly cervical herniated disks. Seventy-six percent of recreational athletes (51/67) age 10 to 42 years RTP in a variety of sports following surgery for mostly herniated disks. No snowboarder returned to snowboarding (0/6) following surgery for cervical fractures. Most professional football players and baseball pitchers returned to their respective sport at their presurgery performance level. Conclusions RTP decisions after cervical spine surgery remain controversial, and there is a paucity of existing literature on this topic. Successful return to competitive sports is well described after single-level anterior cervical diskectomy and fusion surgery for herniated disk. RTP outcomes involving other cervical spine diagnoses and surgical procedures remain unclear. Additional quality research is needed on this topic. PMID- 26835209 TI - Delayed Onset of Subdural Hematoma following Epidural Catheter Breakage. AB - Study Design Case report. Objectives To describe a case of delayed-onset spinal hematoma following the breakage of a spinal epidural catheter. Methods The authors describe the clinical case review. Results A 64-year-old woman had undergone epidural anesthesia 18 years before she was referred to our hospital because of lower-back pain and lower neurologic deficit with leg pain. The clinical examination showed the presence of a fragment of an epidural catheter in the thoracolumbar canal, as assessed by computed tomography, and a spinal hematoma that compressed the spinal cord at the same spinal level, as assessed by magnetic resonance imaging. Surgical removal of the epidural catheter and decompression surgery were performed. The patient exhibited substantial clinical improvement 1 month after surgery; she achieved a steady gait without the need for a cane and had no leg pain. Conclusion This is the first report of delayed onset of spinal hematoma following the breakage of an epidural catheter. Generally, when the breakage of an epidural catheter occurs without symptoms, follow-up alone is recommended. However, because spinal hematoma might exhibit a late onset, the possibility of this complication should be considered when deciding whether to remove the catheter fragment. We believe that in our patient, there could be a relationship between the catheter fragment and subdural hematoma, and catheter breakage could have been a risk factor for the spinal hematoma. PMID- 26835210 TI - Refractory Thoracolumbar Cerebrospinal Fluid Leak after Multiple Spinal Ependymoma Resections Treated with External Ventricular Drainage. AB - Study Design Case report. Objective Temporary external ventricular drainage for refractory thoracolumbar cerebrospinal fluid (CSF) leak is not reported in the literature. We describe a recent case that utilized this technique. Methods Retrospective review of the patient's case notes was performed and the literature on this subject reviewed. Results The patient underwent multiple complex spinal surgeries for resection of innumerable metastatic ependymoma lesions. A case of significant refractory CSF leak developed and as a last resort a right frontal external ventricular drain was placed. The CSF leak ceased, and the patient was eventually discharged home without further complication. Conclusion External ventricular drainage can be a viable option for temporary proximal CSF diversion to treat refractory thoracolumbar CSF leaks. PMID- 26835211 TI - Traumatic Migration of the Bryan Cervical Disc Arthroplasty. AB - Study Design Case study. Objective To describe a case of dislodgment and migration of the Bryan Cervical Disc (Medtronic Sofamor Danek, Memphis, Tennessee, United States) arthroplasty more than 6 months after implantation secondary to low-energy trauma. Methods The inpatient, outpatient, and radiographic medical records of a patient with traumatic migration of the Bryan Cervical Disc arthroplasty were reviewed. The authors have no relevant disclosures to report. Results A 36-year-old man with chronic left upper extremity radiculopathy underwent uncomplicated Bryan Cervical Disc arthroplasty at C5-C6, with complete resolution of his symptoms. Approximately 6 months after his index procedure, he sustained low-energy trauma to the posterior cervical spine, after being struck by a book falling from a shelf. The injury forced his neck into flexion, and though he did not have recurrence of his radiculopathy symptoms, radiographs demonstrated anterior migration of the arthroplasty device. He underwent revision to anterior cervical diskectomy and fusion. Conclusions Although extremely rare, it is imperative that surgeons consider the potential for failure of osseous integration in patients undergoing cervical disk arthroplasty, even beyond 3 to 6 months postoperatively. This concern is especially relevant to press-fit or milled devices like the Bryan Cervical Disc arthroplasty, which lack direct fixation into adjacent vertebral bodies. We are considering modification of our postoperative protocol to improve protection of the device after implantation, even beyond 3 months postoperatively. PMID- 26835212 TI - Anterior Reconstruction of C2-C3 Bodies in a 6-Year-Old Patient with a Huge Osteoblastoma: A Novel Technique. AB - Study Design Case report. Objective We report the youngest child diagnosed with upper cervical osteoblastoma and the first case operated on with our novel surgical approach. Methods Our patient underwent a two-stage surgery. During the first operation via a posterior approach, a subtotal resection of a C2 bony mass was performed. C3 was also subtotally resected due to tumor extension. Posterior fixation of C1-C5 was performed by C1 sublaminar hooks and C4 and C5 lateral mass screws. Ten days later, a total resection of the residual bony mass was performed through an anterior approach (between the sternocleidomastoid muscle and carotid sheath). Reconstruction of C1-C3 was performed with C1 anterior sublaminar wiring and an expandable titanium cage. Results Successful reconstruction of C2-C3 vertebral bodies was achieved. At 2-year follow-up, the child was symptom-free. Imaging studies revealed no recurrence of tumor or instability. Conclusion A novel technique for reconstruction of C2-C3 vertebral bodies is demonstrated for the youngest case (a 6-year-old boy) of osteoblastoma in the literature. We recommend this approach for cervical spine reconstruction in patients who have an intact C1 arc and resected lower bodies. PMID- 26835213 TI - Cervical Ligamentum Flavum Hematoma: A Case Report. AB - Study Design Case report. Objective To report the first case of ligamentum flavum hematoma after cervical spine instrumentation 11 years after the index surgery. Methods After performing bilateral C3 and C4 laminectomy, we observed a dark greenish discoloration over the ligamentum flavum, which was opened. We evacuated 15 mL of subacute hematoma. Results The first ligamentum flavum hematoma of the cervical spine that occurred after spinal instrumentation with sublaminar hooks. Conclusion Ligamentum flavum hematoma might happen even after a long delay (in our case, 11 years) from spinal instrumentation (sublaminar hooks). In symptomatic patients, evacuation is the treatment of choice. In cases of instrument adhesion to the surrounding intracanal tissues, removal should be done meticulously after performing a complete release. PMID- 26835214 TI - Posterior-Only Circumferential Decompression and Reconstruction in the Surgical Management of Lumbar Vertebral Osteomyelitis. AB - Study Design Case report. Objective The purpose of this report is to discuss the surgical management of lumbar vertebral osteomyelitis with a spinal epidural abscess (SEA) and present a single-stage, posterior-only circumferential decompression and reconstruction with instrumentation using an expandable titanium cage and without segmental nerve root sacrifice as an option in the treatment of this disease process. Methods We report a 42-year-old man who presented with 3 days of low back pain and chills who rapidly decompensated with severe sepsis following admission. Magnetic resonance imaging of his lumbosacral spine revealed intramuscular abscesses of the left paraspinal musculature and iliopsoas with SEA and L4 vertebral body involvement. The patient failed maximal medical treatment, which necessitated surgical treatment as a last resort for infectious source control. He underwent a previously undescribed procedure in the setting of SEA: a single-stage, posterior-only approach for circumferential decompression and reconstruction of the L4 vertebral body with posterior segmental instrumented fixation. Results After the surgery, the patient's condition gradually improved; however, he suffered a wound dehiscence necessitating a surgical exploration and deep wound debridement. Six months after the surgery, the patient underwent a revision surgery for adjacent-level pseudarthrosis. At 1-year follow-up, the patient was pain-free and off narcotic pain medication and had returned to full activity. Conclusion This patient is the first reported case of lumbar osteomyelitis with SEA treated surgically with a single-stage, posterior-only circumferential decompression and reconstruction with posterior instrumentation. Although this approach is more technically challenging, it presents another viable option for the treatment of lumbar vertebral osteomyelitis that may reduce the morbidity associated with an anterior approach. PMID- 26835215 TI - The Use of Bone Morphogenetic Protein in Pediatric Cervical Spine Fusion Surgery: Case Reports and Review of the Literature. AB - Study Design Case report. Objective There is a paucity of literature describing the use of bone graft substitutes to achieve fusion in the pediatric cervical spine. The outcomes and complications involving the off-label use of bone morphogenetic protein (BMP)-2 in the pediatric cervical spine are not clearly defined. The purpose of this article is to report successful fusion without complications in two pediatric patients who had instrumented occipitocervical fusion using low-dose BMP-2. Methods A retrospective review of the medical records was performed, and the patients were followed for 5 years. Two patients under 10 years of age with upper cervical instability were treated with occipitocervical instrumented fusion using rigid occipitocervical fixation techniques along with conventionally available low-dose BMP-2. A Medline and PubMed literature search was conducted using the terms "bone morphogenetic protein," "BMP," "rh-BMP2," "bone graft substitutes," and "pediatric cervical spine." Results Solid occipitocervical fusion was achieved in both pediatric patients. There were no reported perioperative or follow-up complications. At 5 year follow-up, radiographs in both patients showed successful occipital cervical fusion without evidence of instrumentation failure or changes in the occipitocervical alignment. To date, there are few published reports on this topic. Complications and the appropriate dosage application in the pediatric posterior cervical spine remain unknown. Conclusions We describe two pediatric patients with upper cervical instability who achieved successful occipital cervical fusion without complication using off-label BMP-2. This report underscores the potential for BMP-2 to achieve successful arthrodesis of the posterior occipitocervical junction in pediatric patients. Use should be judicious as complications and long-term outcomes of pediatric BMP-2 use remain undefined in the existing literature. PMID- 26835216 TI - Transcutaneous Drainage of Gel-Like Substance after Application of Hydrogel Dural Sealant: Report of Two Cases. AB - Study Design Case report. Objective Incidental durotomy (IDT) is a common complication of spinal surgery. The use of collagen matrix graft along with hydrogel dural sealant is a common method of IDT repair. With this method, there have been several reported cases of detrimental dural sealant expansion in the literature. One case study reported an expansion rate greater than 300%; many report neurologic damage. This article reports the clinical course of two patients who developed postoperative transcutaneous drainage of a gel-like substance after the use of a dural sealant, which is a previously unreported complication. Methods The clinical course and treatment outcome of two patients is presented. Results Both patients experienced postoperative transcutaneous drainage of a gel-like substance at the surgical site. Case one began draining this substance on postoperative day 14. This patient required no further intervention, and the drainage ended after 3 mL of a gel-like substance was expressed from his incision while in the clinic. Case two began draining the gel on postoperative day 16. This patient underwent two washout procedures and resolution of the drainage. No infection was ever detected. Conclusions To our knowledge, our patients are the first reported cases of transcutaneous drainage of expanded dural sealant. It is important to take into consideration the unexpected expansion of a dural sealant when using it for the repair of IDT. PMID- 26835217 TI - Inhibitory effects of tibial nerve stimulation on bladder neurophysiology in rats. AB - Tibial nerve stimulation (TNS) is a form of peripheral neuromodulation which has been found effective in treating overactive bladder symptoms, with lesser side effects than first line pharmacotherapy. Despite its widespread clinical use, the underlying mechanism of action is not fully understood. Our aim was to study its effect on the bladder neurophysiology and the trigger mechanism of voiding in the overactive detrusor, simulated by acetic acid (AA) instillation. In urethane anaesthetized male Wistar rats, the tibial nerve was stimulated for 30 min at 5 Hz, pulse width 200 us and amplitude approximately three times the threshold to induce a slight toe movement. The pressure at which a voiding contraction was triggered (pthres) did not change significantly between the pre- and post-TNS measurements in AA induced detrusor overactivity. It was found that TNS significantly reversed the effects of AA irritation by increasing the bladder compliance and the bladder volume at pthres, as well as suppressed the threshold afferent nerve activity. The slope of the linear relationship between pressure and the afferent activity increased after AA instillation and decreased significantly after stimulation. In addition to its well-known central inhibitory mechanisms, this study has demonstrated that TNS improves bladder storage capacity by delaying the onset of voiding, via an inhibitory effect on the bladder afferent signaling at the peripheral level. PMID- 26835218 TI - Oxidative changes in the blood and serum albumin differentiate rats with monoarthritis and polyarthritis. AB - Adjuvant arthritis in rats, as rheumatoid arthritis in humans, may be of greater or lesser severity, namely polyarthritis and monoarthritis, respectively. The present study was planned to evaluate the oxidative changes in the blood and specifically in the serum albumin of rats with adjuvant-induced mono- and poly arthritis. Total antioxidant capacity, thiols, carbonyl groups, albumin, uric acid and ascorbic acid were measured in the total serum. The specific oxidative status of albumin was also measured after separation by affinity chromatography. All serum oxidative parameters were close to normal in monoarthritic rats with the exception of the ascorbic acid concentration, which was 23 % lower, and albumin carbonyl groups, which were 64 % higher. Many modifications were found in polyarthritic rats, specially the ascorbic acid concentration (35 % lower) and albumin carbonyl groups (102 % higher). The results revealed that the levels of ascorbic acid in the serum and carbonyl groups in the albumin molecule can be regarded as indicators of the severity of arthritis since they were modified by both monoarthritis and polyarthritis, but to different degrees. PMID- 26835219 TI - Separation of transglutaminase by thermo-responsive affinity precipitation using l-thyroxin as ligand. AB - Transglutaminase (TGase) is widely used in the food industry. In this study, TGase was purified by affinity precipitation using l-thyroxin, coupled to a thermo-responsive polymer (PNBN), as an affinity ligand. The lower critical solution temperature and recovery of the affinity polymer were 31.0 degrees C and 99.6 %, respectively. The optimal adsorption condition was 0.02 mol/L phosphate buffer (pH 5.0). The recoveries 99.01 % (protein) and 98.85 % (activity) were obtained by 0.2 mol/L Gly-NaOH buffer (pH 10.0) as the elution agent. Circular dichroism spectroscopy and ForteBio Octet system were used to explore the interactions between l-thyroxin and TGase. The results show that l thyroxin is suitable for affinity precipitation of TGase. The purity of the final product was verified using sodium dodecyl sulfate polyacrylamide gel electrophoresis. PMID- 26835220 TI - An overview of platforms for cloud based development. AB - This paper provides an overview of the state of the art technologies for software development in cloud environments. The surveyed systems cover the whole spectrum of cloud-based development including integrated programming environments, code repositories, software modeling, composition and documentation tools, and application management and orchestration. In this work we evaluate the existing cloud development ecosystem based on a wide number of characteristics like applicability (e.g. programming and database technologies supported), productivity enhancement (e.g. editor capabilities, debugging tools), support for collaboration (e.g. repository functionality, version control) and post development application hosting and we compare the surveyed systems. The conducted survey proves that software engineering in the cloud era has made its initial steps showing potential to provide concrete implementation and execution environments for cloud-based applications. However, a number of important challenges need to be addressed for this approach to be viable. These challenges are discussed in the article, while a conclusion is drawn that although several steps have been made, a compact and reliable solution does not yet exist. PMID- 26835221 TI - Alcohol and breast cancer tumor subtypes in a Spanish Cohort. AB - Although alcohol intake is an established risk factor for overall breast cancer, few studies have looked at the relationship between alcohol use and breast cancer risk by the four major subtypes of breast cancer and very few data exist in the alcohol-breast cancer relationship in Spanish women. A population-based case control study was conducted in Galicia, Spain. A total of 1766 women diagnosed with invasive breast cancer between 1997 and 2014 and 833 controls participated in the study. Data on demographics, breast cancer risk factors, and clinico pathological characteristics were collected. We examined the alcohol-breast cancer association according to the major breast cancer subtypes [hormone receptor-positive, HER2-negative (luminal A); hormone-receptor-positive, HER2 positive (luminal B); hormone-receptor-negative, HER2-negative (TNBC); and hormone-receptor-negative, HER2-positive (HER2 overexpressing)] as well as grade and morphology in Spanish women. With the exception of HER2 overexpressing, the risk of all subtypes of breast cancer significantly increased with increasing alcohol intake. The association was similar for hormonal receptor positive breast cancer, i.e., luminal A and luminal B breast cancer (odds ratio, OR 2.16, 95 % confidence interval, CI 1.55-3.02; and OR 1.98, 95 % CI 1.11-3.53, respectively), and for TNBC (TNBC: OR 1.93, 95 % CI 1.07-3.47). The alcohol-breast cancer association was slightly more pronounced among lobular breast cancer (OR 2.76, 95 % CI 1.62-4.69) than among ductal type breast cancers (OR 2.21, 95 % CI 1.61 3.03). In addition, significant associations were shown for all grades, I, II and III breast cancer (OR 1.98, 95 % CI 1.26-3.10; OR 2.34, 95 % CI 1.66-3.31; and OR 2.16, 95 % CI 1.44-3.25 for Grades I, II and III, respectively). To our knowledge, this is the first study to examine the association of breast cancer subtypes and alcohol intake in Spanish women. Our findings indicate that breast cancer risk increased with increasing alcohol intakes for three out of the four major subtypes of breast cancer. The association was similar for hormonal receptor positive breast cancer, i.e., luminal A and luminal B breast cancer, and for TNBC. The association seemed to be slightly more pronounced for lobular than ductal breast cancers. No differences were detected by grade. PMID- 26835222 TI - The increased ratio of 11beta-hydroxysteroid dehydrogenase type 1 versus 11beta hydroxysteroid dehydrogenase type 2 in chronic periodontitis irrespective of obesity. AB - 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which converts inactive cortisone to active cortisol, has been reported to play an important role in metabolic diseases as well as chronic inflammatory diseases. The involvement of 11beta-HSD1 in chronic periodontitis was investigated in the present study. The relationship between the levels of 11beta-HSD1, chronic periodontitis, and body mass index (BMI) was analyzed. The expression of 11beta-HSD1 mRNA was significantly higher in the chronic periodontitis group than in the control group. Since the expression of 11beta-HSD2, which converts active cortisol to inactive cortisone, was slightly lower in the chronic periodontitis group than in the controls, the ratio of 11beta-HSD1 versus 11beta-HSD2 was significantly higher in the chronic periodontitis group than in the controls. A correlation was not observed between BMI and the level of 11beta-HSD1 or between BMI and the ratio of 11beta-HSD1 versus 11beta-HSD2. These results suggested that an increase in the ratio of 11beta-HSD1 versus 11beta-HSD2 was associated with chronic periodontitis irrespective of obesity. PMID- 26835223 TI - ZD7288, a blocker of the HCN channel family, increases doubling time of mouse embryonic stem cells and modulates differentiation outcomes in a context dependent manner. AB - Pluripotent stem cells are the starting cell type of choice for the development of many cell-based regenerative therapies due to their rapid and unlimited proliferation and broad differentiation potential. The unique pluripotent cell cycle underlies both these properties. Hyperpolarization-activated cyclic nucleotide-gated cation (HCN) family channels have previously been reported to modulate mouse embryonic stem cell (ESC) proliferation and here we characterize the effects of HCN inhibitor ZD7288 on ESC proliferation and stem cell identity. The doubling time of cells treated with the HCN blocker increased by ~30 % due to longer G1 and S phases, resulting in a nearly twofold reduction in ESC numbers after 4 day serum-free culture. Slower progression through S phase was not accompanied by H2AX phosphorylation or cell stalling at transition points, although EdU incorporation in treated cells was reduced. Despite the drastic cell cycle perturbations, the pluripotent status of the cells was not compromised by treatment. Cultures treated with the HCN blocker in maintenance conditions maintained pluripotency marker expression on both RNA and protein level, although we observed a reversible effect on morphology and colony formation frequency. Addition of ZD7288 in differentiating media improved FBS-driven differentiation, but not directed differentiation to neuroectoderm, further indicating that altered cell cycle structure does not necessarily compromise pluripotency and drive ESCs to differentiation. The categorically different outcomes of ZD7288 use during differentiation indicate that cell culture context can be determinative for effects of ion-modulatory molecules and underscores the need for exploring their action in serum-free conditions demanded by potential clinical use. PMID- 26835224 TI - Time prediction model of subway transfer. AB - Walking time prediction aims to deduce waiting time and travel time for passengers and provide a quantitative basis for the subway schedule management. This model is founded based on transfer passenger flow and type of pedestrian facilities. Chaoyangmen station in Beijing was taken as the learning set to obtain the relationship between transfer walking speed and passenger volume. The sectional passenger volume of different facilities was calculated related to the transfer passage classification. Model parameters were computed by curve fitting with respect to various pedestrian facilities. The testing set contained four transfer stations with large passenger volume. It is validated that the established model is effective and practical. The proposed model offers a real time prediction method with good applicability. It can provide transfer scheme reference for passengers, meanwhile, improve the scheduling and management of the subway operation. PMID- 26835226 TI - Abnormal 18F-FDG uptakes in the prostate due to two different conditions of urine reflux: a mimicker of prostate cancer. AB - A 69-year-old man with lung cancer underwent 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for staging. FDG PET/CT showed high uptakes in the prostate gland with calcification, and magnetic resonance imaging was recommended to check the prostatic malignancy. T2-weighted images revealed midline cystic lesion at the base to midgland level and cystic lesion in right apical peripheral zone. We suspected urine reflux conditions. Voiding cystourethrography demonstrated those cystic lesions were communicating with the urethra. Therefore these lesions were diagnosed as the prostatic utricle cyst and the dilated prostatic duct in peripheral zone. We conclude that the urine reflux condition should be recognized as a prostate benign lesion with FDG accumulation. PMID- 26835225 TI - A phase II study of afatinib, an irreversible ErbB family blocker, added to letrozole in patients with estrogen receptor-positive hormone-refractory metastatic breast cancer progressing on letrozole. AB - Phase II, open-label study assessing the efficacy and safety of the ErbB family blocker afatinib combined with letrozole in estrogen receptor-positive metastatic breast cancer (MBC) patients who had progressed on letrozole monotherapy. Adult females (N = 28) received oral afatinib (50 [n = 7], 40 [n = 13] or 30 [n = 8] mg/day) plus letrozole 2.5 mg/day in 28-day cycles until disease progression. Primary endpoint was the progression-free rate at or after 16 weeks of afatinib. At 16 weeks, four patients remained on afatinib without progression; two of these were HER2 negative. Fifteen (54 %) patients had a best response of stable disease according to Response Evaluation Criteria in Solid Tumors. Median progression free survival was 60, 107 and 79 days with 50, 40 and 30 mg/day afatinib, respectively. Diarrhea, asthenia, rash, mucosal inflammation and nausea were the most frequent adverse events. In this small, exploratory study, afatinib combined with letrozole was able to induce disease stabilization in 54 % of hormone refractory MBC patients previously progressing on letrozole. CLINICAL TRIAL REGISTRATION: NCT00708214. PMID- 26835227 TI - Comparisons of outcomes in stroke subtypes after intravenous thrombolysis. AB - The purpose of this study was to analyze the outcomes and complications between stroke subtypes after intravenous thrombolysis. A total of 471 patients with acute ischemic stroke after intravenous thrombolysis from January 2007 to April 2014 were enrolled and classified according to the Trial of Org 10172 in Acute Stroke Treatment. A multivariate logistic regression model was used to evaluate the outcomes and complications among stroke subtypes after adjusting for baseline variables. Of the 471 patients, 117 (25.1 %) had large-artery atherosclerosis (LAA), 148 (31.8 %) had cardioembolism (CE), 82 (17.6 %) had small vessel disease (SVD), 119 (25.5 %) had undetermined etiology, and 5 (1.1 %) had other determined etiology. The patients with SVD had the mildest initial stroke severity and highest ratio of good and favorable outcomes, whereas those with CE had a higher rate of symptomatic intracranial hemorrhage (sICH) than those with SVD. After adjusting for confounding factors, the ratio of favorable outcome in the patients with SVD stroke was higher than in those with LAA. SVD was associated with a significantly lower rate of any hemorrhage compared to other stroke subtypes, whereas there were no differences in sICH or mortality between stroke subtypes. A lower initial National Institutes of Health Stroke Scale score was associated with good and favorable outcomes, and lower rates of sICH and mortality. The patients with SVD after intravenous thrombolysis had better outcomes and a lower rate of hemorrhage even after adjusting for confounding factors. Stroke severity was an independent factor associated with better functional outcomes, sICH and mortality. PMID- 26835228 TI - Immobilization of cellulase on a silica gel substrate modified using a 3-APTES self-assembled monolayer. AB - Cellulase was immobilized onto silica gel surfaces pretreated with (3 aminopropyl) triethoxy-silane (3-APTES), and glutaraldehyde (GA) was used as a cross-linker. A carboxymethyl cellulose sodium salt (CMC) solution was used for activity experiments. Protein assay was performed to determine the mass immobilized and compare with free enzyme. Cellulase was successfully demonstrated to be immobilized on the modified silica gel surface, and no detectable amount of enzyme was stripped off during the hydrolysis of the CMC solution. The specific activity of the immobilized cellulase is 7 +/- 2 % compared to the similar amount of free cellulase. Significant activity over multiple reuses was observed. The seventh batch achieved 82 % activity of the initial batch, and the fifteenth batch retained 31 %. It was observed that the immobilized cellulase retained 48 % of its initial activity after 4 days, and 22 % even after 14 days. PMID- 26835229 TI - On some Hermite-Hadamard type inequalities for (s, QC)-convex functions. AB - In the paper, the authors introduce a new notion "[Formula: see text]-convex function on the co-ordinates" and establish some Hermite-Hadamard type integral inequalities for [Formula: see text]-convex functions on the co-ordinates. PMID- 26835230 TI - Effect and clinical significance of fast-track surgery combined with laparoscopic radical gastrectomy on the plasma level of vascular endothelial growth factor in gastric antrum cancer. AB - This study discusses the effect and clinical significance of fast-track surgery (FTS) combined with laparoscopic radical surgery on the plasma level of vascular endothelial growth factor (VEGF) in locally advanced gastric antrum cancer. Plasma VEGF levels were detected in 63 cases of locally advanced gastric antrum cancer by using double-antibody sandwich Avidinbiotincomplex-ELISA before and after operation. The pure laparoscopic surgery group (group A) comprised 30 cases, and the combined FTS group (group B) consisted of 33 cases. Results of the two groups were obtained at similar time points and then compared. The VEGF levels were not significantly different between the two groups on the first day before the operation and on the first day, third day, and sixth month after the operation (P > 0.05). However, the differences were significant on the seventh day and first month after the operation (P < 0.05). The postoperative eating time, anal exhaust time, and hospital stay of the patients were statistically significantly different between the two groups (P < 0.05). Nevertheless, no significant differences were detected in terms of wound healing time and complications (P > 0.05). The 3-year survival rate significantly differed between the two groups (P < 0.05). FTS combined with laparoscopic surgery can decrease the postoperative VEGF level compared with pure laparoscopic surgery. The combined approach improved postoperative recovery without prolonging the wound healing time or increasing the incidence of postoperative complications. The 3 year survival rate also increased. Thus, FTS combined with laparoscopic surgery can improve the prognosis in gastric antrum cancer. PMID- 26835231 TI - Cerebral hemodynamics is altered in patients with sleep apnea/hypopnea syndrome. AB - According to recent epidemiologic studies, patients with sleep apnea/hypopnea syndrome (SAHS) are at increased risk of cardiovascular diseases, including stroke. However, the mechanisms are not well defined. Nocturnal apneas can trigger acute cerebral ischemia in predisposed patients and impaired vasodilatation is present in SAHS, but few studies have explored vascular cerebral dysfunction and often gave inconclusive results. The aims of our study were to assess whether patients with SAHS have impairment of cerebral hemodynamics with respect to controls, and to investigate a possible relationship with clinical data. We studied two groups, one of 76 SAHS patients and another one of 76 non-SAHS subjects matched for age, sex and main cardiovascular risk factors. All participants underwent a daytime transcranial Doppler study of right middle cerebral artery to record cerebral blood flow velocity and cerebrovascular reactivity by means of breath-holding test (BHT). SAHS patients have a reduction in mean cerebral blood flow velocity (MFV) (52 +/- 9 vs 60 +/- 12 cms/s, p < 0.001) and BHT (31 +/- 12 vs 36 +/- 11 %, p = 0.005) when compared to non-SAHS controls. Moreover, MFV correlated negatively with the presence of coronary disease, and BHT with female sex and arterial pressure. On the other hand, in the SAHS group, MFV correlated negatively with oxygen desaturation severity. Patients with SAHS have impaired MFV and cerebrovascular reactivity when compared to controls. Interestingly, poorly controlled or unknown hypertension and severe nocturnal hypoxemia caused additional cerebral hemodynamic disturbances to these patients. PMID- 26835232 TI - Exchange transfusion for neonate with haemolytic uremic syndrome. AB - INTRODUCTION: Haemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in children but it is uncommon in newborns. To our knowledge only five cases have been reported so far (probably underreported). The known modalities of treatment include transfusion of plasma and plasmapheresis. We report a case of neonatal HUS for whom we performed an exchange transfusion to good effect. CASE DESCRIPTION: A term vaginally born baby, meconium stained and floppy at birth presented with severe anaemia in the first few hours of life. The baby later on developed renal failure and blood picture was suggestive of severe thrombocytopenia and microangiopathic haemolytic anaemia. No extra renal manifestations of birth asphyxia were noted. A double volume exchange transfusion was performed relatively early and subsequently platelet and haemoglobin stabilised and renal failure improved. DISCUSSION AND EVALUATION: The clinical impression in this case was convincing of neonatal HUS, likely attributable to birth asphyxia but needs to be differentiated from disseminated intravascular coagulation (DIC) and thrombotic thrombocytopenic purpura (TTP). The coagulation profile is usually normal in HUS but it is abnormal in DIC, whereas in TTP one would find hyperbilirubinemia, increased creatinine, haemolysis etc. TTP is rare but not very uncommon in infancy. Congenital TTP is attributed to an inherent deficiency of ADAMTS-13, which is a vWF-cleaving metalloprotease. Irrespective of the etiology of HUS in our case, a dramatic response was observed with exchange transfusion. Transfusion of fresh frozen plasma (FFP) and plasmapheresis are known treatment modalities. FFP replaces the missing or altered complement factors and plasmapheresis removes antibodies, immune complexes and toxins. An exchange transfusion combines both these functions. CONCLUSIONS: In the absence of facilities for plasmapheresis, exchange transfusion is a good alternative. PMID- 26835233 TI - Serum alpha-klotho concentrations during preimplantation can predict aging or quality of human oocytes and clinical pregnancy rates. AB - BACKGROUND: To discover simple biomarkers to evaluate the aging or quality of human oocytes and clinical pregnancy rates is needed. However, the association among serum alpha-klotho concentrations during preimplantation, the aging or quality of human oocytes and clinical pregnancy rates has not been investigated. FINDINGS: The serum alpha-klotho concentrations during preimplantation decreased due to aging (p < 0.001), whereas the maturation rates of human oocytes (p < 0.001) and the fertilization rates (p < 0.001) improved in association with increased serum alpha-klotho concentrations. Furthermore, multiple logistic regression analysis showed that the clinical pregnancy rates were influenced by serum alpha-klotho concentrations during preimplantation (p < 0.001), the patient's age (p = 0.003), maturation rates of human oocytes (p < 0.001), fertilization rates (p < 0.001) and the serum 25 (OH) D levels (p < 0.001) regardless of race (p = 0.29) and BMI (p = 0.96). CONCLUSION: The serum alpha klotho concentrations during preimplantation would be a simple biomarker in order to predict the aging or quality of human oocytes and clinical pregnancy rates. PMID- 26835234 TI - Comparison of various texture classification methods using multiresolution analysis and linear regression modelling. AB - Textures play an important role in image classification. This paper proposes a high performance texture classification method using a combination of multiresolution analysis tool and linear regression modelling by channel elimination. The correlation between different frequency regions has been validated as a sort of effective texture characteristic. This method is motivated by the observation that there exists a distinctive correlation between the image samples belonging to the same kind of texture, at different frequency regions obtained by a wavelet transform. Experimentally, it is observed that this correlation differs across textures. The linear regression modelling is employed to analyze this correlation and extract texture features that characterize the samples. Our method considers not only the frequency regions but also the correlation between these regions. This paper primarily focuses on applying the Dual Tree Complex Wavelet Packet Transform and the Linear Regression model for classification of the obtained texture features. Additionally the paper also presents a comparative assessment of the classification results obtained from the above method with two more types of wavelet transform methods namely the Discrete Wavelet Transform and the Discrete Wavelet Packet Transform. PMID- 26835235 TI - New building blocks or dendritic pseudopeptides for metal chelating. AB - Dendritic oligopeptides have been reported as useful building blocks for many interactions. Starting from hydrazine, we described an approach to create new dendritic pseudopeptides linked with biological systems, such as cell membrane, as chelate metal, Ni(2+)-nitrilotriacetic acid moieties which could target histidine rich peptides or proteins. Depending on the nature of these new chemical recognition units, they could be integrated into a peptide by coupling in C or N-termini.Graphical abstract:Dendrimer formation. PMID- 26835236 TI - Surmounting a PCR challenge using a Contradictory matrix from the Theory of Inventive Problem Solving (TRIZ). AB - In this paper I tested whether Contradictory Matrix with 40 Inventive Principles, the simplest instrument from the Theory of Inventive Problem Solving (TRIZ), is a useful approach to a real-life PCR scenario. The PCR challenge consisted of standardization of fluorescence melting curve measurements in Competitive Amplification of Differentially Melting Amplicons (CADMA) PCR for multiple targets. Here I describe my way of using the TRIZ Matrix to generate seven alternative solutions from which I can choose the successful solution, consisting of repeated cycles of amplification and melting in a single PCR run. PMID- 26835237 TI - Towards smart energy systems: application of kernel machine regression for medium term electricity load forecasting. AB - Integration of energy systems with information technologies has facilitated the realization of smart energy systems that utilize information to optimize system operation. To that end, crucial in optimizing energy system operation is the accurate, ahead-of-time forecasting of load demand. In particular, load forecasting allows planning of system expansion, and decision making for enhancing system safety and reliability. In this paper, the application of two types of kernel machines for medium term load forecasting (MTLF) is presented and their performance is recorded based on a set of historical electricity load demand data. The two kernel machine models and more specifically Gaussian process regression (GPR) and relevance vector regression (RVR) are utilized for making predictions over future load demand. Both models, i.e., GPR and RVR, are equipped with a Gaussian kernel and are tested on daily predictions for a 30-day-ahead horizon taken from the New England Area. Furthermore, their performance is compared to the ARMA(2,2) model with respect to mean average percentage error and squared correlation coefficient. Results demonstrate the superiority of RVR over the other forecasting models in performing MTLF. PMID- 26835239 TI - Paradoxes in dynamic stability of mechanical systems: investigating the causes and detecting the nonlinear behaviors. AB - A critical review of three paradoxical phenomena, occurring in the dynamic stability of finite-dimensional autonomous mechanical systems, is carried out. In particular, the well-known destabilization paradoxes of Ziegler, due to damping, and Nicolai, due to follower torque, and the less well known failure of the so called 'principle of similarity', as a control strategy in piezo-electro mechanical systems, are discussed. Some examples concerning the uncontrolled and controlled Ziegler column and the Nicolai beam are discussed, both in linear and nonlinear regimes. The paper aims to discuss in depth the reasons of paradoxes in the linear behavior, sometimes by looking at these problems in a new perspective with respect to the existing literature. Moreover, it represents a first attempt to investigate also the post-critical regime. PMID- 26835238 TI - Eribulin in pretreated metastatic breast cancer patients: results of the TROTTER trial-a multicenter retrospective study of eribulin in real life. AB - This retrospective multicenter analysis was aimed to evaluate clinical activity and tolerability of eribulin in pretreated metastatic breast cancer patients in clinical practice. Patients treated with eribulin from January 2012 to July 2013 were enrolled in the observational study from 10 italian hospitals. Tumor and toxicity evaluation were performed according to Agenzia Italiana Farmaco. One hundred and thirteen patients were included in the study. Median age 62 years old. 71.7 % of the patients had visceral involvement and the majority had a burden of disease involving two or more organs with a median number of 2 (1-6). The median number of previous chemotherapy regimens for advanced disease was 3 (1 10). Median number of eribulin cycles was 4 (1-27). Overall response rate was 24 % (95 % CI 16.0-31.8). Clinical benefit rate, was 35.4 % (95 % CI 26.6-44.2). At a median follow-up of 29.6 months (8.3-41.9) the median progression free survival was 3.3 months (0.6-26.7; 95 % CI 2.4-4.2), and the median overall survival 11.6 months (0.6-33.3; 95 % CI 8.7-14.5). No correlation was recorded between subtypes in terms of ORR and CBR. Toxicity was manageable. Main common grade 3-4 toxicities were neutropenia (19.4 %), febrile neutropenia (0.9 %), asthenia (3.5 %), abnormal liver function test (1.8 %), stomatitis (0.9 %). Our results confirm that treatment with eribulin is feasible and safe in real-world patients. PMID- 26835240 TI - To Be Imported or to Be Endemic? That is the Question. PMID- 26835241 TI - Assessment of Antisecretory, Gastroprotective, and In-vitro Antacid Potential of Daucus carota in Experimental Rats. AB - OBJECTIVES: In Indo China, carrots have been reported to regulate the functions of the stomach and intestines. The objective of the present investigation was to unravel the therapeutic potential of 50% ethanol extract from Daucus carota roots (EDC) on antisecretory, gastroprotective, and in vitro antacid capacity using experimental rats. METHODS: Assessment of EDC antisecretory and in vivo antacid capacities was carried out using a pyloric ligation induced ulcer model. The gastroprotective effect was assessed with an absolute ethanol induced ulcer model. The integrity of gastric mucosa was evaluated using the estimation of glutathione and gastric mucus level and with histopathological examination of gastric mucosal cells. The in-vitro antacid capacity was evaluated using a titration method. The effect of the extract on the liver was assessed by measuring serum biochemical parameters. RESULTS: The EDC significantly (p < 0.01 0.001) reduced gastric lesions in both models. Furthermore, the EDC also significantly (p < 0.05-0.001) reduced the volume of gastric content whereas the total acidity was significantly (p < 0.05-0.001) reduced with the doses of 100 mg/kg and 200 mg/kg EDC. Moreover, the mucus content and glutathione level increased significantly (p < 0.05) in the absolute alcohol-induced ulcer. The EDC also showed in-vitro antacid capacity. Histopathological studies further confirmed the potential of EDC by inhibiting congestion, edema, hemorrhage, and necrosis in gastric mucosa. CONCLUSION: The EDC exerted antisecretory, gastroprotective, and in vitro antacid potential. These activities could be attributed due to the presence of glycosides, phenolics, tannins, alkaloids, and flavonoids. PMID- 26835242 TI - Cloning, Expression, and Purification of Hyperthermophile alpha-Amylase from Pyrococcus woesei. AB - OBJECTIVES: In an attempt alpha-amylase gene from Pyrococcus woesei was amplified and cloned into a pTYB2 vector to generate the recombinant plasmid pTY- alpha amylase. METHODS: Escherichia coli BL21 used as a host and protein expression was applied using IPTG. SDS-PAGE assay demonstrated the 100 kDa protein. Amylolytic activity of proteins produced by transformed E. coli cells was detected by zymography, and the rate of active alpha-amylase with and without the intein tag in both soluble conditions and as inclusion bodies solubilized by 4M urea were measured. RESULTS: Amylolytic activity of ~185,000 U/L of bacterial culture was observed from the soluble form of the protein using this system. CONCLUSION: These results indicate that this expression system was appropriate for the production of thermostable alpha-amylase. PMID- 26835243 TI - Epidemiological Characterization of Skin Fungal Infections Between the Years 2006 and 2010 in Korea. AB - OBJECTIVES: The purpose of this study was to build and provide a basic database of skin fungal infections for the effective management of skin fungal infections in the future. METHODS: We collected health insurance data between the years 2006 and 2010 from the Health Insurance Corporation (Seoul, Korea) and analyzed the data to determine the prevalence and treatment management of skin fungal infections. RESULTS: Skin fungal infections were divided into two groups: namely dermatophytosis and other superficial mycoses. Dermatophytosis showed a higher prevalence (16,035,399 cases) than the other superficial mycoses (794,847 cases) within the study period. The prevalence rate decreased consecutively by 0.01% to 0.19% every year. The prevalence according to region showed that Jeolla-do had a high prevalence distribution. The prevalences in men and women were similar (7.01% vs. 6.26%). It is interesting to note that adults from the 50-79-year age group showed a higher prevalence than children and young adults. The average convalescence time (days) of dermatophytosis was longer than that of other superficial mycoses. The total medical expenses were also much higher in dermatophytosis than in the other superficial mycoses. CONCLUSION: This study provides useful data for study trends of skin fungal infections. PMID- 26835244 TI - Prevalence of Head Lice Infestation and Its Associated Factors among Primary School Students in Iran: A Systematic Review and Meta-analysis. AB - OBJECTIVES: Head lice infestation is one of the most important health problems, generally involving children aged 5-13 years. This study aims to estimate the prevalence of head lice infestation and its associated factors among primary school children using systematic review and meta-analysis methods. METHODS: Different national and international databases were searched for selecting the relevant studies using appropriate keywords, Medical Subject Heading terms, and references. Relevant studies with acceptable quality for meta-analysis were selected having excluded duplicate and irrelevant articles, quality assessment, and application of inclusion/exclusion criteria. With calculating standard errors according to binomial distribution and also considering the Cochrane's Q test as well as I-squared index for heterogeneity, pediculosis prevalence rate was estimated using Stata SE V.11 software. RESULTS: Forty studies met the inclusion criteria of this review and entered into the meta-analysis including 200,306 individuals. Using a random effect model, the prevalence (95% confidence interval) of head lice infestation among primary school children was estimated as 1.6% (1.2-2.05), 8.8% (7.6-9.9), and 7.4% (6.6-8.2) for boys, girls, and all the students, respectively. The infestation rate was found to be associated with low educational level of parents, long hair, family size, mother's job (housewife), father's job (worker/unemployed), using a common comb, lack of bathrooms in the house, and a low frequency of bathing. CONCLUSION: This meta-analysis revealed that the prevalence of head lice infestation among Iranian primary school children is relatively high with more prevalence among girls. We also found that economic, social, cultural, behavioral, and hygienic factors are associated with this infestation. PMID- 26835245 TI - Effect of Repeated Freezing and Thawing on Biomarker Stability in Plasma and Serum Samples. AB - OBJECTIVES: The stability of circulating proteins can be affected by repeated freezing and thawing. The aim of our study was to identify the effect of repeated freezing and thawing on the plasma and serum concentrations of eight proteins [interferon-gamma, interleukin (IL)-8, IL-15, IL-17A, matrix metalloproteinase (MMP)-7, tumor necrosis factor-alpha, vascular endothelial growth factor (VEGF), and VEGF receptor 2 (VEGF-R2)]. METHODS: We assessed the concentration changes of these proteins in 30 plasma and serum samples subjected to three, four, or five freeze-thaw cycles, and compared these with the concentration changes in the samples that were subjected to two freeze-thaw cycles before analysis. RESULTS: Repeated freezing and thawing by up to five cycles did not modify the plasma and serum concentrations of interferon-gamma, IL-8, and VEGF-R2, while levels of MMP 7, tumor necrosis factor-alpha, and VEGF were significantly changed in both plasma and serum samples. Moreover, MMP-7 and VEGF concentrations tended to increase with freeze-thaw cycles. They were more elevated in plasma samples (up to about 15%) than in serum samples (up to about 7%), suggesting that serum is the preferred sample type for the analysis of circulating proteins. CONCLUSION: This is the first report on the effect of repeated freezing and thawing on plasma concentrations of MMP-7 and VEGF-R2. Our findings propose that researchers should consider the number of freeze-thaw cycles to select plasma or serum samples, depending on the type of analyte. PMID- 26835246 TI - Imported Melioidosis in South Korea: A Case Series with a Literature Review. AB - OBJECTIVES: Melioidosis is a potentially fatal infectious disease caused by the environmental anaerobic Gram-negative bacillus Burkholderia pseudomallei. Melioidosis is endemic to areas of northern Australia and Southeast Asia. With increasing international travel and migration, imported cases of melioidosis are being reported regularly. Here, we summarize the 11 cases of melioidosis reported in South Korea from 2003 to 2014. METHODS: Tracing epidemiological investigations were performed on every patient reported to the National Surveillance System since 2011. A systematic literature search was performed to identify melioidosis cases that occurred prior to 2011. RESULTS: The overall fatality rate was 36.4%. All the patients had visited Southeast Asia where melioidosis is endemic. The stay in the endemic region ranged from 4 days to 20 years. Of the seven patients who developed initial symptoms after returning to South Korea, the time interval between returning to South Korea and symptom onset ranged from 1 day to 3 years. The remaining four patients developed symptoms during their stay in the endemic region and were diagnosed with melioidosis in South Korea. Seven (63.6%) patients possessed at least one risk factor, all of whom were diabetic. Pneumonia was the most frequent clinical manifestation, but the patients showed a wide spectrum of clinical features, including internal organ abscesses, a mycotic aneurysm of the aorta, and coinfection with tuberculosis. CONCLUSION: An early diagnosis and initiation of the appropriate antibiotics can reduce the mortality of melioidosis. Consequently, increased awareness of the risk factors and clinical features of melioidosis is required. PMID- 26835247 TI - N-terminal amphipathic helix of Amphiphysin can change the spatial distribution of immunoglobulin E receptors (FcepsilonRI) in the RBL-2H3 mast cell synapse. AB - Biomembranes undergo extensive shape changes as they perform vital cellular functions or become diseased. To understand the mechanisms by which lipids and proteins control membrane curvature during various processes, researchers have identified and engineered many curvature-inducing and curvature-sensing proteins and peptides. In this paper, a simple experiment was performed to show qualitatively how membrane remodeling by N-terminal amphipathic helix of Amphiphysin affects the spatial distribution of the transmembrane Fc receptor protein (FcepsilonRI) in mast cells. Results indicate that an elevated concentration of amphipathic helices can interfere with the formation of a typical mast cell synapse. PMID- 26835248 TI - Self-reported and accelerometer-measured physical activity by body mass index in US Hispanic/Latino adults: HCHS/SOL. AB - The association between obesity and physical activity has not been widely examined in an ethnically diverse sample of Hispanic/Latino adults in the US. A cross-sectional analysis of 16,094 Hispanic/Latino adults 18-74 years was conducted from the multi-site Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Body mass index (BMI) was measured and categorized into normal, overweight, and obese; underweight participants were excluded from analyses. Physical activity was measured using the 16-item Global Physical Activity Questionnaire and by an Actical accelerometer. Minutes/day of physical activity and prevalence of engaging in >= 150 moderate-vigorous physical activity (MVPA) minutes/week were estimated by BMI group and sex adjusting for covariates. No adjusted differences were observed in self-reported moderate (MPA), vigorous (VPA), or MVPA across BMI groups. Accelerometry-measured MPA, VPA, and MVPA were significantly higher for the normal weight (females: 18.9, 3.8, 22.6 min/day; males: 28.2, 6.1, 34.3 min/day, respectively) compared to the obese group (females: 15.3, 1.5, 16.8 min/day; males: 23.5, 3.6, 27.1 min/day, respectively). The prevalence of engaging in >= 150 MVPA minutes/week using accelerometers was lower compared to the self-reported measures. Efforts are needed to reach the Hispanic/Latino population to increase opportunities for an active lifestyle that could reduce obesity in this population at high risk for metabolic disorders. PMID- 26835249 TI - Endo- and ectoparasites of large whales (Cetartiodactyla: Balaenopteridae, Physeteridae): Overcoming difficulties in obtaining appropriate samples by non- and minimally-invasive methods. AB - Baleen and sperm whales, belonging to the Order Cetartiodactyla, are the largest and heaviest existent mammals in the world, collectively known as large whales. Large whales have been subjected to a variety of conservation means, which could be better monitored and managed if physiological and pathophysiological information, such as pathogen infections, could already be gathered from free swimming animals instead of carcasses. Parasitic diseases are increasingly recognized for their profound influences on individual, population, and even ecosystem health. Furthermore, a number of parasite species have gained importance as opportunistic neozoan infections in the marine environment. Nonetheless, traditional approaches to study parasitic diseases have been impractical for large whales, since there is no current routine method for the capture and handling of these large animals and there is presently no practical method to obtain blood samples remotely from free-ranging whales. Therefore, we here not only intend to review the endo- and ectoparasite fauna of large whales but also to provide new insights in current available methods for gathering parasitological data by using non- or minimally invasive sampling techniques. We focus on methods, which will allow detailed parasitological studies to gain a broader knowledge on parasitoses affecting wild, free-swimming large whale populations. PMID- 26835250 TI - Manifold habitat effects on the prevalence and diversity of avian blood parasites. AB - Habitats are rapidly changing across the planet and the consequences will have major and long-lasting effects on wildlife and their parasites. Birds harbor many types of blood parasites, but because of their relatively high prevalence and ease of diagnosis, it is the haemosporidians - Plasmodium, Haemoproteus, and Leucocytozoon - that are the best studied in terms of ecology and evolution. For parasite transmission to occur, environmental conditions must be permissive, and given the many constraints on the competency of parasites, vectors and hosts, it is rather remarkable that these parasites are so prevalent and successful. Over the last decade, a rapidly growing body of literature has begun to clarify how environmental factors affect birds and the insects that vector their hematozoan parasites. Moreover, several studies have modeled how anthropogenic effects such as global climate change, deforestation and urbanization will impact the dynamics of parasite transmission. This review highlights recent research that impacts our understanding of how habitat and environmental changes can affect the distribution, diversity, prevalence and parasitemia of these avian blood parasites. Given the importance of environmental factors on transmission, it remains essential that researchers studying avian hematozoa document abiotic factors such as temperature, moisture and landscape elements. Ultimately, this continued research has the potential to inform conservation policies and help avert the loss of bird species and threatened habitats. PMID- 26835251 TI - Past, present and future of host-parasite co-extinctions. AB - Human induced ecosystem alterations and climate change are expected to drive several species to extinction. In this context, the attention of public opinion, and hence conservationists' efforts, are often targeted towards species having emotional, recreational and/or economical value. This tendency may result in a high number of extinctions happening unnoticed. Among these, many could involve parasites. Several studies have highlighted various reasons why we should care about this, that go far beyond the fact that parasites are amazingly diverse. A growing corpus of evidence suggests that parasites contribute much to ecosystems both in terms of biomass and services, and the seemingly paradoxical idea that a healthy ecosystem is one rich in parasites is becoming key to the whole concept of parasite conservation. Although various articles have covered different aspects of host-parasite co-extinctions, I feel that some important conceptual issues still need to be formally addressed. In this review, I will attempt at clarifying some of them, with the aim of providing researchers with a unifying conceptual framework that could help them designing future studies. In doing this, I will try to draw a more clear distinction between the (co-)evolutionary and the ecological dimensions of co-extinction studies, since the ongoing processes that are putting parasites at risk now operate at a scale that is extremely different from the one that has shaped host-parasite networks throughout million years of co-evolution. Moreover, I will emphasize how the complexity of direct and indirect effects of parasites on ecosystems makes it much challenging to identify the mechanisms possibly leading to co-extinction events, and to predict how such events will affect ecosystems in the long run. PMID- 26835252 TI - Host manipulation in the face of environmental changes: Ecological consequences. AB - Several parasite species, particularly those having complex life-cycles, are known to induce phenotypic alterations in their hosts. Most often, such alterations appear to increase the fitness of the parasites at the expense of that of their hosts, a phenomenon known as "host manipulation". Host manipulation can have important consequences, ranging from host population dynamics to ecosystem engineering. So far, the importance of environmental changes for host manipulation has received little attention. However, because manipulative parasites are embedded in complex systems, with many interacting components, changes in the environment are likely to affect those systems in various ways. Here, after reviewing the ecological importance of manipulative parasites, we consider potential causes and consequences of changes in host manipulation by parasites driven by environmental modifications. We show that such consequences can extend to trophic networks and population dynamics within communities, and alter the ecological role of manipulative parasites such as their ecosystem engineering. We suggest that taking them into account could improve the accuracy of predictions regarding the effects of global change. We also propose several directions for future studies. PMID- 26835255 TI - Translational Pediatrics-Message from the Editor-in-Chief. PMID- 26835256 TI - Vitamin D is a friend of younger children. PMID- 26835254 TI - INFLUENCE OF DIABETES ON AMBULATION AND INFLAMMATION IN MEN AND WOMEN WITH SYMPTOMATIC PERIPHERAL ARTERY DISEASE. AB - OBJECTIVE: To determine whether diabetes and sex were factors associated with ambulatory function, endothelial cell inflammation, oxidative stress, and apoptosis, and with circulating biomarkers of inflammation and antioxidant capacity in patients with peripheral artery disease (PAD) and claudication. MATERIALS/METHODS: Ambulatory function of 180 symptomatic men and women with PAD was assessed during a graded maximal treadmill test, 6-minute walk test, and 4 meter walk test. Patients were further characterized on endothelial effects of circulating factors present in the sera using a cell culture-based bioassay on primary human arterial endothelial cells, and on circulating inflammatory and vascular biomarkers. RESULTS: Men and women with diabetes had greater prevalence (p = 0.007 and p = 0.015, respectively) of coronary artery disease (CAD) than patients without diabetes. To assure that this difference did not influence planned comparisons, the data set was stratified on CAD. Diabetic men with CAD had a lower peak walking time (PWT) during the treadmill test and a slower 4 meter gait speed compared to non-diabetic men with CAD (p < 0.05). Diabetic women with CAD had a lower PWT compared to their non-diabetic counterparts (p < 0.01). Additionally, diabetic men with CAD had higher pigment epithelium-derived factor (p < 0.05) than their non-diabetic counterparts, and diabetic women with CAD had higher leptin (p < 0.01) and interleukin-8 levels (p < 0.05). CONCLUSIONS: In patients with PAD, diabetic men and women with CAD had more severe claudication than their non-diabetic counterparts, as measured by shorter PWT, and the men had further ambulatory impairment manifested by slower 4-meter gait speed. Furthermore, the diabetic patients with CAD had elevations in interleukin-8, leptin, and PEDF. PMID- 26835253 TI - Climate change, biodiversity, ticks and tick-borne diseases: The butterfly effect. AB - We have killed wild animals for obtaining food and decimated forests for many reasons. Nowadays, we are burning fossil fuels as never before and even exploring petroleum in deep waters. The impact of these activities on our planet is now visible to the naked eye and the debate on climate change is warming up in scientific meetings and becoming a priority on the agenda of both scientists and policy decision makers. On the occasion of the Impact of Environmental Changes on Infectious Diseases (IECID) meeting, held in the 2015 in Sitges, Spain, I was invited to give a keynote talk on climate change, biodiversity, ticks and tick borne diseases. The aim of the present article is to logically extend my rationale presented on the occasion of the IECID meeting. This article is not intended to be an exhaustive review, but an essay on climate change, biodiversity, ticks and tick-borne diseases. It may be anticipated that warmer winters and extended autumn and spring seasons will continue to drive the expansion of the distribution of some tick species (e.g., Ixodes ricinus) to northern latitudes and to higher altitudes. Nonetheless, further studies are advocated to improve our understanding of the complex interactions between landscape, climate, host communities (biodiversity), tick demography, pathogen diversity, human demography, human behaviour, economics, and politics, also considering all ecological processes (e.g., trophic cascades) and other possible interacting effects (e.g., mutual effects of increased greenhouse gas emissions and increased deforestation rates). The multitude of variables and interacting factors involved, and their complexity and dynamism, make tick-borne transmission systems beyond (current) human comprehension. That is, perhaps, the main reason for our inability to precisely predict new epidemics of vector-borne diseases in general. PMID- 26835257 TI - Children's Oncology Group L991 final study report: Establishing an important benchmark for assessing late effects of trimodality care of pediatric patients treated for high grade gliomas. PMID- 26835258 TI - Vitamin D intake in young children with acute lower respiratory infection. AB - OBJECTIVE: To determine if vitamin D intake is associated with acute lower respiratory infections (ALRI) in children. METHODS: The vitamin D intakes of children younger than 5 years of age admitted to hospital with either bronchiolitis or pneumonia were compared to an unmatched control group of the same age without respiratory infection. Caregivers of 197 children completed a questionnaire collecting information on demographic variables, ALRI risk factors and diet. Associations of ALRI with vitamin D intake and other ALRI risk factors were determined. RESULTS: The mean vitamin D intake of children with ALRI was 48 IU/kg/d compared to 60 IU/kg/d in the control group. When controlling for age, ethnicity, socio-economic status, northern residence, breastfeeding, immunizations and smoking contact, children with a vitamin D intake of less than 80 IU/kg/d were greater than 4 times more likely to have ALRI compared to children with a vitamin D intake exceeding 80 IU/kg/day (OR 4.9, 95% CI: 1.5, 16.4). CONCLUSIONS: A higher vitamin D intake than currently recommended might be needed to offer protection against diseases such as ALRI. Increased vitamin D supplementation could have important public health consequences, as bronchiolitis and pneumonia are the most common reasons for hospitalization in young children. PMID- 26835260 TI - A pilot trial on the treatment of gastroesophageal reflux-related cough in infants. AB - BACKGROUND: Diagnosing asthma in infancy is largely made on the basis of the symptoms of cough and wheeze. A similar presentation can be seen in neurologically normal infants with excessive gastroesophageal reflux (GER). There are no randomized placebo controlled studies in infants using proton pump inhibitors (PPI) alone or in addition to prokinetic agents. OBJECTIVES: The primary objective was to confirm the presence of excessive GER in a population of infants that also had respiratory symptoms suggestive of asthma. Second, in a randomized placebo-controlled fashion, we determined whether treatment of GER with bethanacol and omeprazole could improve these respiratory symptoms. METHODS: Infants (n=22) with a history of chronic cough and wheeze were enrolled, if they had evidence of GER by history and an abnormal pH probe or gastric emptying scan. Infants were randomly allocated to four treatment groups: placebo/placebo (PP), omeprazole plus bethanacol (OB), omeprazole/placebo (OP), bethanacol/placebo (BP). Evaluations by clinic questionnaire and exam, home diary, and pH probe data were done before, after study-medication and after open label of OB. RESULTS: Nineteen children were studied. PP did not affect GER or respiratory symptoms, and did not decrease GER measured by pH probe. In contrast, OB decreased GER as measured by pH probe indices and parental assessment. In association, OB significantly decreased daytime coughing and improved respiratory scores. No adverse effects were reported. CONCLUSIONS: In infants with a clinical presentation suggestive of chronic GER-related cough, the use of omeprazole and bethanacol appears to be viable therapeutic option. PMID- 26835262 TI - Effectiveness and safety of methylphenidate and atomoxetine for attention deficit hyperactivity disorder: a systematic review. AB - OBJECTIVE: To assess and compare the effectiveness and safety of methylphenidate immediate-release tablets (IR-MPH), methylphenidate controlled-release tablets (OROS-MPH) and atomoxetine (AHC) for attention deficit hyperactivity disorder (ADHD) in Chinese children. METHODS: Randomized or clinical controlled trials on the effectiveness and safety of IR-MPH, OROS-MPH and AHC for ADHD were searched in electronic databases of CNKI, VIP, CBMDISC online, PubMed, Embase and MEDLINE. Two reviewers independently extracted the data and assessed the quality of the included literatures. RESULTS: Eight trials were finally included. IR-MPH, OROS MPH and AHC were effective for ADHD. OROS-MPH was superior to IR-MPH in the improvement of peer relationship, CGI-I score, mother satisfaction and psychosomatic problems. There were no significant differences in the effectiveness between the AHC and IR-MPH groups. The adverse events related to the therapy with IR-MPH, OROS-MPH or AHC were mild and total incidence rates of adverse events was not significantly different among the three groups. CONCLUSIONS: The effectiveness of OROS-MPH for the treatment of ADHD is probably superior to IR-MPH, and the effectiveness of AHC and IR-MPH is similar. The three drugs have equivalent safety and good tolerance. PMID- 26835263 TI - Fluid therapy of brain edema and intracranial hypertension in children. PMID- 26835261 TI - Management of children after renal transplantation: highlights for general pediatricians. AB - The number of children undergoing successful renal transplantations has been increasing steadily and as a result; general pediatricians are now more likely to encounter children with a kidney allograft in their practice. Although the medical care immediately after transplantation is mostly provided by transplant teams, more and more outpatient care will eventually be performed at the patient's local community. Medical care from general pediatricians is particularly important, especially for children who are residing far from transplant centers. As these children require prolong immunosuppressive therapies and are susceptible to various specific clinical problems, it is imperative for their primary care providers and pediatricians to be knowledgeable about their specific needs and be competent in providing care. This article highlights the roles and common practice related issues that pertain to general pediatricians in the care of pediatric renal allograft recipients. PMID- 26835264 TI - Integrative genomics reveals molecular and clinical heterogeneity in central nervous system primitive neuroectodermal tumors in children. PMID- 26835259 TI - Epidemiologic survey on hospitalized neonates in China. AB - OBJECTIVE: To carry out a nationwide epidemiologic survey on the neonates in urban hospitals with an attempt to understand the disease spectrum and treatment outcomes of hospitalized neonates in China. METHODS: The clinical data of 43,289 hospitalized neonates from 86 hospitals in 47 Chinese cities (22 provinces) between January 1, 2005 and December 31, 2005 were retrospectively analyzed. RESULTS: The male:female ratio was 1.73:1. Premature infants accounted for 26.2% of the hospitalized neonates, which was higher than that reported in 2002 (19.7%). The top three diseases during the neonatal period were jaundice, pneumonia, and hypoxic-ischemic encephalopathy. The incidences of pneumonia, meconium aspiration syndrome, and bilirubin encephalopathy in term infants were higher than those in premature infants, while the incidences of asphyxia, respiratory distress syndrome, and pulmonary hemorrhage in term infants were lower than those in premature infants. The incidences of asphyxia, small for gestational age infant, and wet lung were higher in neonates whose mother had pregnancy induced hypertension. The outcomes of these hospitalized neonates included: recovered, 63.9%; improved, 27.3%; discharged due to the family's own decisions, 7.6%, and died, 1.2%. Nearly half (46.4%) of the neonatal death occurred within 24 hrs after admission. CONCLUSION: The incidence of premature birth shows an increasing trend among hospitalized neonates. Since the neonatal deaths mainly occur within 24 hrs after admission, monitoring during this period should be enhanced. PMID- 26835265 TI - Vertebral compression fractures during chemotherapy for childhood acute lymphoblastic leukemia: commentary on a report from the STeroid Associated Osteoporosis in the Pediatric Population (STOPP) research program. PMID- 26835266 TI - A step forward in acute lymphoblastic leukemia. PMID- 26835267 TI - A survey of neonatal births in the maternal departments in urban China 2005. AB - OBJECTIVE: The authors studied the epidemiology of births in urban China. STUDY DESIGN: The authors conducted a retrospective study using data from the perinatal dataset of women delivering live births in 2005 at the maternity departments of 72 hospitals from 47 urban areas of 22 provinces in China. RESULTS: A total of 45,722 infants born from Jan 1, 2005 to Dec 31, 2005 were enrolled. (I) Male to female ratio was 1.13:1; (II) 8.1% of infants were born preterm; (III) The incidence of very low birth weight infants was 0.7%; (IV) A total of 99.7% of women delivering at term were naturally conceived and 0.3% had experienced assisted reproduction. Whereas 1.6% in women delivering preterm had assisted reproductive; (V) The total cesarean delivery rate was 49.2% compared to 50.8% of vaginal birth. Most cesarean delivery (38.1%) were due to social factors; (VI) Overall, 4.8% of infants had an Apgar of less than 7 at 1 minute, 1.6% less than 7 at 5 minutes; (VII) Of all the infants, 7.14% were admitted to neonatal units and death rate was 0.74% in all infants. CONCLUSIONS: The proportion of preterm births was still higher in 2005 than that in 2002 and total caesarian delivery rate was much higher in urban China than that in America as well as most Asia countries. PMID- 26835268 TI - MRI-DWI improves the early diagnosis of brain abscess induced by Candida albicans in preterm infants. AB - OBJECTIVE: To investigate the diagnostic value of magnetic resonance imaging (MRI) in brain abscess induced by invasive fungal infection (IFI) of the central nervous system. METHODS: The clinical data of eight preterm infants with IFI of the central nervous system were retrospectively analyzed. All these eight children received three sequential brain MRI modes T1WI, T2WI and DWI during hospitalization and after discharge. RESULTS: All these eight preterm infants were infected with Candida albicans, seven of which were manifested by brain abscess and four were accompanied by meningitis. MRI of seven infants with brain abscess indicated extensive invasion including involvement of subcortical white matter, deep periventricular white matter and semiovale center white matter. MRI examination was conducted within 11 d following infection on four cases and showed diffuse or multiple miliary nodules, hyper-intense signal on DWI, while insignificant signal changes on T1WI and T2WI. DWI signal nearly disappeared three weeks later. T1WI/T2WI signal changed most significantly 2-4 weeks following infection, with nodules ring-shaped, hyper-intense signal around T1WI and hypo-intense signal in the center. Signal on T2WI was just on the opposite. Severe cases presented fusion of different degrees. Significant enhanced effect was observed on T1WI. Four weeks later, the lesion gradually became fewer and smaller on T1WI, transferred into dot or line-like hyper-intense signal and presented obviously hypo-intense signal on T2WI. Dynamic MRI of two cases showed delayed myelination and corpus callosum thinning. CONCLUSION: MRI-DWI and dynamic MRI changes can improve the early diagnosis of brain abscess induced by Candida albicans in preterm infants. PMID- 26835269 TI - Cloning and sequence analysis of SLC25A13 transcripts in human amniocytes. AB - OBJECTIVE: To amplify the entire ORF of SLC25A13 cDNA which encodes citrin, a liver-type mitochondrial aspartate-glutamate carrier, and to investigate sequence feature of the transcripts for this gene in cultured human amniocytes. This study will provide laboratory evidences for prenatal diagnosis of NICCD at mRNA level. METHODS: Total RNA was extracted from cultured amniocytes, and cDNA was synthesized, and then nest PCR was performed to amplify the entire ORF sequences of SLC25A13. The PCR products were purified, cloned, sequenced, and aligned with the genomic DNA of SLC25A13 to analyze the alternative splicing pattern. RESULTS: The entire ORF of SLC25A13 gene was successfully amplified. Three splice variants of SLC25A13, i.e., SLCA (normal mRNA), SLCB (CAG insertion between exon 9-10) and SLCC (exon 5-11 skipping), were identified in the subjects. However, no abnormal mRNA from the allele with mutation 851del4 was detected in the amniocytes cultured from a carrier fetus of this mutation. CONCLUSIONS: This study demonstrated that the entire ORF of SLC25A13 cDNA can be successfully amplified from cultured human amniocytes, and revealed exon 5-11 skipping as a novel SLC25A13 transcript. Normal mRNA occupied majority of the transcripts in normal control and heterozygous amniocytes which contained normal allele and 851del4 mutation, indicating that the two fetuses wouldn't suffer from NICCD. These SLC25A13 transcription features provided laboratory evidences for prenatal diagnosis of NICCD. PMID- 26835270 TI - Site-directed mutagenesis of neonatal convulsions associated KCNQ2 gene and its protein expression. AB - OBJECTIVE: To study the protocol of construction of a KCNQ2-c.812G>T mutant and its eukaryotic expression vector, the c.812G>T (p.G271V) mutation, which was detected in a Chinese pedigree of benign familial infantile convulsions (BFIC), and to examine the expression of mutant protein in human embyonic kidney (HEK) 293 cells. METHODS: A KCNQ2 mutation c.812G>T was engineered on KCNQ2 cDNAs cloned into pcDNA3.0 by sequence overlap extension PCR and restriction enzymes. HEK293 cells were co-transfected with pRK5-GFP and KCNQ2 plasmid (the wild type or mutant) using lipofectamine and then subjected to confocal microscopy. The transfected cells were immunostained to visualize the intracellular expression of the mutant molecules. RESULTS: Direct sequence analysis revealed a G to T transition at position 812. The c.812G>T mutation was correctly combined to eukaryotic expressive vector pcDNA3.0 and expressed in HEK293 cells. Immunostaining of transfected cells showed the expression of both the wild type and mutant molecules on the plasma membrane, which suggested that the c.812G>T mutation at the pore forming region of KCNQ2 channel did not impair normal protein expression in HEK293 cells. CONCLUSIONS: Successful construction of mutant KCNQ2 eukaryotic expression vector and expression of KCNQ2 protein in HEK293 cells provide a basis for further study on the functional effects of convulsion-causing KCNQ2 mutations and for understanding the molecular pathogenesis of epilepsy. PMID- 26835271 TI - Treatment of Kawasaki disease by different doses of immunoglobulin: a meta analysis of efficacy and safety. AB - OBJECTIVE: To assess the efficacy and safety of different doses of immunoglobulin in the treatment of Kawasaki disease (KD). METHODS: The papers related to the treatment of KD were electronically searched in the databases including PubMed, EMBASE, Cochrane Library, CNKI, VIP and Wanfang. Randomized clinical trials (RCT) on the treatment of KD with different doses of immunoglobulin were included and assessed for quality. A Mata analysis was performed by RevMan 5.0. RESULTS: Twenty-eight RCTs involving 2,596 cases were included. The results of Meta analysis showed that there were no significant differences in the incidences of coronary artery injuries at various phases, adverse reactions, and fever disappearance time between the immunoglobulin treatment groups at the doses of 1 g/(kg*d) for 1-2 days or 2 g/(kg*d) for single use. The fever disappearance time in the immunoglobulin treatment group at the dose of 1 g/(kg*d) for 1-2 days was significantly shorter than that in the immunoglobulin treatment group at the dose of 400 mg/(kg*d) for 4-5 days, but there were no significant differences in the incidences of coronary artery injuries at the acute phase and 6 months after treatment and in the adverse effects between the two groups. The incidence of coronary artery injuries at the acute phase and 6 months after treatment was significantly lower and the fever disappearance time was significantly shorter in the immunoglobulin treatment group at the dose of 2 g/(kg*d) for single use than those in the immunoglobulin treatment group at the dose of 400 mg/(kg*d) for 4-5 days, but there were no significant differences in the incidences of coronary artery injuries at the subacute phase and 12 months after treatment and adverse effects between the two groups. CONCLUSIONS: There are similar efficacy for KD between the immunoglobulin treatment groups at the doses of 1 g/(kg*d) for 1-2 days and 2 g/(kg*d) for single use. The fever disappearance time in the two groups is shorter than that in the treatment group at the dose of 400 mg/(kg*d) for 4-5 days. PMID- 26835273 TI - Pediatric high-grade gliomas: survival at what cost? PMID- 26835272 TI - Research advances in neonatal hypoglycemic brain injury. PMID- 26835274 TI - Is quarterly bolus vitamin D3 supplementation adequate to prevent childhood pneumonia? PMID- 26835275 TI - Improving outcomes in childhood T-cell acute lymphoblastic leukemia: promising results from the Children's Oncology Group incorporating nelarabine into front line therapy. PMID- 26835276 TI - Neurocognitive function and CNS integrity in adult survivors of childhood Hodgkin Lymphoma - a commentary on report from Krull and colleagues. PMID- 26835277 TI - New gene signatures for pediatric brain tumors: a step forward in the understanding of molecular basis of CNS PNET. PMID- 26835278 TI - Role of notch signal in angiotensin II induced pulmonary vascular remodeling. AB - OBJECTIVE: Notch signal is particularly important to vascular remodeling during the process of embryonic development, vessel repair and tumor growth, but there are few studies about pulmonary vascular remodeling in pulmonary hypertension. This study was to explore the effect of inhibiting Notch signal on pulmonary vascular remodeling induced by angiotensin II. METHODS: Vessel strips taken from healthy Wistar rats were cocultured with extrogenous angiotensin II and the potent smooth muscle cell proliferation stimulators for 7 days. Vascular wall thickness, proliferating cell nuclear antigen (PCNA) positive cell rate, and caspase-3 positive cell rate were examined in vessel strips. Some of the vessel strips were cultured with angiotensin II and gamma-secretase inhibitor DAPT, a Notch signaling inhibitor, for 7 days. The levels of Notch 1 to 4 receptor and HERP1/2 mRNA were ascertained by FQ-PCR. RESULTS: Angiotensin II stimulation in the cultured normal pulmonary arteries resulted in an increase in the vascular medial thickness by nearly 50%, and a significant increase in the PCNA positive cell rate and a decrease in the caspase-3 positive cell rate (P<0.05). DAPT treatment did not alter the levels of Notch 1 to 4 receptor but remarkably decreased HERP1 and HERP2 mRNA expression (P<0.05). DAPT treatment also decreased angiotensin II-induced vascular medial thickness and PCNA positive cell rate, and increased caspase-3 positive cell rate (P<0.05). CONCLUSIONS: Inhibition of Notch signal by the gamma-secretase inhibitor may suppress pulmonary vascular remodeling induced by angiotensin II, suggesting that the inhibition of Notch signal pathway might be a novel strategy for the treatment of pulmonary hypertension. PMID- 26835279 TI - HIF-1alpha siRNA reduces retinal neovascularization in a mouse model of retinopathy of prematurity. AB - OBJECTIVE: To explore the effect of HIF-1alpha specific siRNA expression vector pSUPERH1-siHIF-1alpha on retinal neovascularization in a mouse model of retinopathy of prematurity (ROP). METHODS: Forty-eight newborn C57BL/6J mice were randomly divided into the control and experimental groups (n=24 apiece) to create the model of ROP following the methods described by Smith et al. Twelve days after birth, the experimental group received intravitreal injection with pSUPERH1 siHIF-1alpha; meanwhile, mice in the control group were injected with empty vectors. The expressions of HIF-1alpha and vascular endothelia growth factor (VEGF) in the retina were examined by Western blotting in both groups. The differences in the neovascular endothelial cell count were compared based on the FITC-Dextran fluorescence stretched preparation/sections. RESULTS: Compared with the control group, the expressions of HIF-1alpha and VEGF significantly decreased in the experimental group (P<0.01). Meanwhile, the number of retinal neovascular endothelial nuclei that had protruded the internal limiting membrane was significantly lower in the experimental group than in control group (P<0.01). CONCLUSIONS: RNA interference targeting HIF-1alpha can effectively inhibit the retinal neovascularization of ROP. PMID- 26835280 TI - Epidemiological survey on newborns born at the obstetric departments in hospitals in mid-southern region of China in 2005. AB - OBJECTIVE: To investigate the situations at birth of newborns in the mid-southern region of China by performing a survey on the newborns born at urban hospitals. METHODS: A total of 23 hospitals in the mid-southern region of China were selected to participate in this survey. The data of 15,582 newborns who were born at the obstetric departments from January 1, 2005 to December 31, 2005 were retrospectively investigated. RESULTS: The male to female ratio among newborns was 1.16:1. The incidence of preterm birth was 8.11%, while very low birth weight (VLBW) infants accounted for 0.73%. The rates of spontaneous vaginal delivery and cesarean section ware 57.52% and 40.82%, respectively, while the other delivery modes accounted for 1.66%. The incidence of neonatal asphyxia was 3.78% (0.75% for heavy asphyxia). The mortality of newborns was 0.55% (5.56% for preterm infants). CONCLUSIONS: The incidences of preterm birth and neonatal asphyxia are relatively high in the mid-southern region of China. The rate of cesarean section is abnormally high, which is due mainly to social factors. PMID- 26835281 TI - Regulatory T cells and Th1/Th2 in peripheral blood and their roles in asthmatic children. AB - OBJECTIVE: To determine the changes in CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) and the Th1/Th2 ratio in peripheral blood of children with asthma, in order to investigate its association with asthma. METHODS: A total of 150 children with asthma were allocated into the acute phase group (n=94) and remission phase group (n=56) based on clinical manifestations. The acute phase group was subdivided into the mild group (n=54) and severe group (n=40). Flow cytometry was applied to determine CD4(+)CD25(+)Foxp3(+) Treg, CD4(+)IFN-gamma(+) Th1 and CD4(+)IL-4(+) Th2 levels in peripheral blood of different groups, and the results were compared with normal children (control group, n=50). RESULTS: The Treg level was significantly lower in the asthma group than the control group (P<0.01): the Treg level was significantly lower in the acute phase group than the remission phase group and control group (P<0.01) and also significantly lower in the severe group than the mild group (P<0.01). The Th1/Th2 ratio was significantly lower in the asthma group than the control group (P<0.01) and also significantly lower in the acute phase group than the remission phase group and control group (P<0.01). The Treg level in peripheral blood of asthmatic children was negatively correlated with the severity of asthma (r=-0.737, P<0.01) and the Th1/Th2 ratio was also negatively correlated with the severity of asthma (r= 0.615, P<0.01), but the Treg level was positively correlated with the Th1/Th2 ratio (r=0.856, P<0.01). CONCLUSIONS: The significantly decreased level of Treg in peripheral blood and Th subset imbalance in asthmatic children suggest the important roles of Treg and Th immunity in pathogenesis of asthma. The Treg level and Th1/Th2 ratio in peripheral blood can be used to evaluate the severity asthma. PMID- 26835282 TI - Under 5 mortality rate and its contributors in Zhejiang Province of China from 2000 to 2009. AB - OBJECTIVE: By analyzing the under 5 mortality rate (U5MR) and its contributors in Zhejiang Province of China from 2000 to 2009, we tried to understand the trend of U5MR change in Zhejiang Province and thus propose strategies to reduce child mortality. METHODS: Thirty cities/counties/districts from Zhejiang Province were selected using stratified cluster sampling approach. Children under five years in these areas were enrolled as the subjects. The U5MR and its contributors were analyzed in terms of age, migration status of mothers, and other indicators using classic descriptive methods and Chi square test. RESULTS: The U5MR in Zhejiang Province showed a declining trend from 14.830/00 in 2000 to 9.490/00 in 2009. In 2009, the U5MR was significantly higher in the rural areas than in the urban areas (9.140/00 vs.6.500/00, P<0.01) and among floating populations than among local residents (12.120/00 vs. 6.420/00, P<0.01). Preterm birth/low birth weight was the leading cause of U5MR in 2009. More specifically, preterm birth/low birth weight, congenital heart disease, and birth asphyxia were the top three causes of deaths among infants (<1 year), while drowning, traffic accidents, and accidental falls were the leading causes of deaths among children (1-4 years). CONCLUSION: The U5MR in Zhejiang Province in 2009 differed between urban areas and rural areas and between floating populations and local residents. The main causes of death differ between infants and young children. Prevention of preterm birth/low birth weight and congenital anomalies will reduce infant death, while the main intervention for young children is to avoid accidental injuries. PMID- 26835283 TI - Dilemma's regarding vertebral fractures in children with acute lymphoblastic leukemia (ALL). PMID- 26835284 TI - Minimal residual disease detection in pediatric acute myeloid leukemia: does flow cytometry score a point over molecular biology? PMID- 26835285 TI - Omitting pulmonary radiotherapy in selected stage IV nephroblastoma patients with pulmonary metastases. PMID- 26835286 TI - Nonoliguric hyperkalemia in a late preterm infant with severe birth asphyxia. AB - Nonoliguric hyperkalemia (NOHK) is common during the first days after birth in premature infants with gestational age <28 weeks. It was rarely reported in term or late preterm infants. We present a case of a 3 hours baby at 34 weeks and 3 days' gestational age who was delivered of severe birth asphyxia by cesarean section for failing to vaginal delivery. Serum potassium reached to 8.3 mmol/L at 12 hours age, with normal urinary output and serum urea and creatinine. Abnormal ECG of tall peaked T waves was developed. Marked fall in serum Ca(2+) of 0.6 mmol/L and total calcium of 1.13 mmol/L was also noted. Cerebral lesions in the head MRI demonstrated extensive periventricular white matter injury. PMID- 26835287 TI - Neurocognitive function and CNS integrity in adult survivors of childhood Hodgkin lymphoma. PMID- 26835288 TI - Relapsed acute myeloblastic leukemia: first pediatric randomized study. PMID- 26835289 TI - Use of positron emission tomography scanning to evaluate pseudoresponse. PMID- 26835290 TI - Interpretation of the Experts' Consensus on the criteria for the diagnosis and grading of neonatal asphyxia in China. PMID- 26835291 TI - Experts' Consensus on the criteria for the diagnosis and grading of neonatal asphyxia in China. PMID- 26835293 TI - CINSARC: a new look into an old concept gives hope for new treatments for synovial sarcomas. PMID- 26835292 TI - Targeting death receptors: is this trail still hot? PMID- 26835294 TI - Consideration of Glucocorticoids and Escherichia coli-derived L-asparaginase in the treatment of pediatric acute lymphoblastic leukemia. PMID- 26835295 TI - Specificity of problem-solving skills training in mothers of children newly diagnosed with cancer: a commentary on the Bright IDEAS program. PMID- 26835296 TI - How to assess minimal residual disease in pediatric and adult acute myeloid leukemia? PMID- 26835297 TI - Late outcomes of congenital heart disease. AB - In our days, more than 90% of children with congenital heart disease (CHD) reach adolescence and adult life, and therapeutic procedures are performed with late quality of life (QOL) in mind. Rates of success are now assessed at long range by sequels, residues and adaptation of the individuals to normality. The attempt to identify factors to avoid psychopathological sequels in this group of "new" cardiac patients is one of the most important aspects of studies on late outcome of congenital heart disease. This fact remains valid in the current era and is in consonance with the attitude to more and more value child-adolescent and adolescent-adult transitions in patients with CHD submitted or not to surgical or percutaneous intervention in childhood. Resilience and ability to adapt could also be improved by a multiprofessional approach of attitudes, abilities and psychological characteristics, aiming to prevent the psychopathologic effects of the disease. PMID- 26835298 TI - Shall we treat congenital heart lesions, their suffering patients or also their families, and surrounding societal ambience? AB - Results with the treatment of congenital heart defects (CHD) have improved markedly. However these patients, in their teens and adulthood ages, suffer from psychological dysfunctions of different natures, even psychiatric diseases, that must by thought and be properly managed. Not only these dysfunctions are related to clinical history profiles, but they are clearly related to social support, with impacts on the way quality of life (QOL) is perceived. This new vision creates a window of opportunities to act, now, on the aspect of their social modelling and psychological support, to improve QOL and psychological adaptation for these patients, already living longer, in order to make them living better. PMID- 26835299 TI - Long term psychosocial outcomes of congenital heart disease (CHD) in adolescents and young adults. AB - BACKGROUND: Congenital heart disease (CHD) is a chronic illness with a high frequency in the worldwide population, and is normally diagnosed at birth or in uterus. Because of better conditions in diagnosis and early medical and surgical treatment, patients have survival rates of 90% and go further and further in life, facing different challenges in life cycle. In this study, we tested the effects of different demographic, clinical and psychosocial variables on the perception of quality of life (QOL), on psychosocial adjustment (PSA) and psychiatric morbidity (PM) of adolescents and young adults with CHD. OBJECTIVES: We aimed to evaluate QOL, PM and PSA of adolescents and young adults with CHD and to determine which variables (demographic, clinical, and psychosocial) play a role in buffering stress and promoting resilience and which ones have a detrimental effect. METHODS: The study enrolled 150 CHD patients (87 males and 63 females), 12 to 26 years (M: 17.45+/-3.373 years). The participants were interviewed regarding social support, family educational style, self-image, demographic information and physical limitations. They responded to questions in a standardized psychiatric interview (SADS-L) and completed self-reports questionnaires for assessment of QOL (WHOQOL-BREF) and PSA (YSR/ASR). RESULTS: We found an 18.7% lifetime prevalence of psychopathology in our participants (25.4% in females and 13.8% in males). 57.1% had retentions in school (M: 1.53+/-0.804 year). The perception of QOL of CHD patients is better compared to the Portuguese population in the Social Relationships, Environmental, Physical and General Dimensions. However, it is worse in complex forms of CHD, in cyanotic patients, in moderate-to-severe residual lesions, in patients submitted to surgery and in patients with physical limitations. All of these variables, except presence of cyanosis, are also associated to a worse PSA. Social Support is very important in improving QOL of patients in all dimensions as well as academic performance. CONCLUSIONS: Female patients and patients with poor academic performance and poor social support refer worse PSA and QOL. PMID- 26835301 TI - The concept and practice of Fanconi Anemia: from the clinical bedside to the laboratory bench. AB - Fanconi Anemia (FA) is characterised with multiple gene mutations, multiple types of genetic abnormalities, multiple organ involvements and multiple types of cancer risks. It is a life threatening disease commonly at 5 years old children. Research on FA is one of the fastest areas in medical research field. The identification of 15 different FA genes and the elucidation of the FA molecular pathways have translated into the understanding of the pathogenic mechanism and practically provided the directions for therapies. Studies on FA rendered invaluable information for the studies on cancers because FA possesses the unique features in many different biological aspects. Studies revealed the genetic linking between FA and cancers that FA genes are in cancers and cancers genes are in FA. As a result, FA is named as a paradigmatic disease for the understanding of cancer and aging. In clinical practice, an early and accurate diagnosis of FA before the stage of bone marrow failure, cancer/leukemia is crucial for the adequate treatment, the prevention of serious medical complications and also for the properly management in the other caring areas including paediatric, hematology, immunology, endocrinology, reproductive/IVF, obstetrics and surgery. However, an early and accurate diagnosis for FA is often difficult because FA is genetically and phenotypically heterogeneous disease. Diagnosis in more or less cases can be delayed until bone marrow failure or cancer/leukemia occurs. As a result that delayed or misdiagnosis even wrong treatment received for patients with FA are not uncommon events clinically in some regions or countries due to the lack of recognition of FA from the clinicians and the limitation in testing resource in laboratory. In this review, the new concept, brief clinical characteristics, research advancing, diagnostic guidelines/differential diagnosis, laboratory testing issues and strategies on FA are discussed. PMID- 26835302 TI - Pediatric Hodgkin Lymphoma: on the road to a 'radiotherapy-free' cure rate? Commentary on a report on final results of the Multinational Trial GPOH-HD95. PMID- 26835303 TI - Treatment of children and adolescents with Hodgkin's Lymphoma without radiotherapy for patients in complete remission after chemotherapy. PMID- 26835304 TI - Omitting or reducing radiotherapy in childhood or adolescence Hodgkin Lymphoma. AB - Despite high cure rates, treatment of childhood Hodgkin Lymphoma (HL) is associated with late effects caused mainly by radiotherapy (RT). In the GPOH-HD95 trial of the German Society of Pediatric Oncology and Hematology that was recently published in the Journal of Clinical Oncology, RT was spared in patients achieving a stringently defined complete remission (CR) with chemotherapy and reduced in patients with a good partial remission (PR). Overall, RT-treated patients had superior PFS, but overall survival (OS) was almost identical within each risk-stratified treatment group irrespectively of the use of RT. In the low risk group, RT could be safely omitted in 20% of patients. In contrast, failure rates were considered unacceptable, when RT was omitted in intermediate or high risk patients achieving a CR. However, salvage therapy was successful, equalizing overall survival between irradiated and non-irradiated patients. Although GPOH HD95 points out to the omission of RT in selected patients achieving a CR after chemotherapy, especially those in the low-risk group, more than 80% of the patients are still irradiated. Notably, the GPOH-HD95 was not a randomized trial. In conclusion, according to the GPOH-HD95 trial, RT can be safely omitted in pediatric and adolescent patients with low-risk, early stage HL achieving a stringently defined CR after 2 cycles of OPPA or OEPA chemotherapy. RT dose could also be reduced in case of good PR by conventional imaging. However, conventional response assessment is not the optimal means to decide whether RT is needed or not. It is now increasingly recognized that RT can be omitted in many patients with HL without compromising the final outcome and it appears wise to try to stringently limit RT in those patients who really need it. This might be achieved through the use of modern functional imaging (PET/CT). Such efforts are already in progress and results regarding efficacy are awaited relatively soon. PMID- 26835305 TI - Treatment of Hodgkin's lymphoma in childhood and adolescence without radiotherapy. PMID- 26835306 TI - Professor Fengcai Zhu: China leads the EV-71 vaccine research and development. PMID- 26835300 TI - Vitamin D deficiency in surgical congenital heart disease: prevalence and relevance. AB - Vitamin D is a pleiotropic hormone important for the proper functioning of multiple organ systems. An emerging body of adult and pediatric critical care literature strongly suggests that vitamin D deficiency contributes to secondary organ pathophysiology, prolongs ICU stay, and worsens outcome in critically ill populations. Recent clinical studies suggest that a significant number of children with congenital heart disease (CHD) have post-operative vitamin D deficiency which appears to be associated with greater cardiovascular dysfunction. Altogether the cumulative body of literature suggests that peri operative optimization of vitamin D status has the potential to speed recovery and/or improve outcome. This review describes the epidemiological and basic science research linking vitamin D deficiency to post-operative organ dysfunction. Furthermore, the available supplementation approaches are reviewed in the context of prevention of post-operative vitamin D deficiency and avoidance of toxicity in the majority of CHD patients. Finally, knowledge gaps regarding vitamin D supplementation are identified and the next stages for research are outlined. PMID- 26835307 TI - Editorial on the role of "Genetic mediators of neurocognitive outcome in survivors of childhood acute lymphoblastic leukemia". AB - With current chemotherapy regimen favorable event free survival rates can be achieved for children and adolescents with acute lymphoblastic leukemia (ALL). Besides others, neurocognitive late effects come more and more into the focus of attention. Especially, as first reports indicate that the omission of cranial irradiation (CRT) did not solve the problem of neurocognitive deficits. The report by Krull and colleagues analyzed the association of neurocognitive outcome and a large set of potentially predisspoing polymorphisms. The authors identified significant associations between specific polymorphisms and neurocognitive outcome. However, the consequences of such testing need to be discussed carefully. PMID- 26835308 TI - Brain size and neuropsychological functioning in long-term survivors of pediatric acute lymphoblastic leukemia. AB - With the increased survival of pediatric cancer patients the interest in the late effects of treatments is rapidly increasing. Long-term survival rates for children with acute lymphoblastic leukemia (ALL) now approach 90%. Treatment for ALL includes intensified central nervous system (CNS)-directed therapy, which is associated with risks for long-term neurocognitive effects. It is becoming clear that current therapies can have not only a detrimental effect on IQ, processing speed, and memory, but also on structural changes that lead to permanent alterations of the organization of the CNS. Understanding how the CNS is affected by the treatments is a critical step in evaluating current therapies and developing interventions to decrease the incidence and severity of long-term changes in brain anatomy and function. PMID- 26835309 TI - Brain volume and cognitive function in adult survivors of childhood acute lymphoblastic leukemia. AB - The survival rate for childhood acute lymphoblastic leukemia (ALL) is greater than 80%. However, many of these survivors develop long-term chronic health conditions, with a relatively common late effect being neurocognitive dysfunction. Although neurocognitive impairments have decreased in frequency and severity as treatment has evolved, there is a subset of survivors in the current treatment era that are especially vulnerable to the neurotoxic effects of ALL and its treatment. Additionally, little is known about long-term brain development as survivors mature into adulthood. A recent study by Zeller et al. compared neurocognitive function and brain volume in 130 adult survivors of childhood ALL to 130 healthy adults matched on age and sex. They identified the caudate as particularly sensitive to the neurotoxic effects of chemotherapy. We discuss the implications and limitations of this study, including how their findings support the concept of individual vulnerability to ALL and its treatment. PMID- 26835310 TI - Pneumatically-driven external pressure applicator to augment Fontan hemodynamics: preliminary findings. AB - BACKGROUND: This study investigated the application of circumferentially applied, external pressure to the lower extremities as a preventative measure and long term clinical treatment strategy for Fontan patients. OBJECTIVE: We hypothesized that the application of circumferential pressure to the lower limbs will augment venous return and thus cardiac output. METHODS: Two patients (an extra-cardiac and intra-atrial Fontan) were evaluated. Both trials were conducted during a routine cardiac catheterization. The aortic and inferior vena cava (IVC) pressures were recorded. We applied three different external pressures to the lower limbs based on the patient's diastolic pressure. Each pressure was applied with a one-minute rapid inflate/deflate period for a total of five cycles and a rest period between pressure intervals. RESULTS: Patient 1 (age 37, female) demonstrated pressure rises of 10-15 mmHg in both the aortic and IVC pressures. Patient 2 (age 24, male) had undetectable pressure rise during the first pressure cycles and notable pressures rise of approximately 8-12 mmHg during the third cycle. CONCLUSIONS: External pressure application redistributes blood volume or cardiac output as a result of impedance in the lower extremities, enhancing venous pressure and return. Our findings strongly suggest an acute benefit from the implementation of external mechanical compression of the lower vasculature to increase cardiac output in Fontan patients. PMID- 26835311 TI - Changes in interleukin-17 and transforming growth factor beta 1 levels in serum and bronchoalveolar lavage fluid and their clinical significance among children with asthma. AB - OBJECTIVES: To investigate the changes in the levels of interleukin-17 (IL-17) and transforming growth factor beta 1 (TGF-beta1) in serum and bronchoalveolar lavage fluid (BALF) and their clinical significance among children with asthma. METHODS: A total of 56 children with asthma were divided into moderate or severe asthma (n=37) and mild asthma groups (n=19) and 18 children without asthma were selected as the control group. Cells in BALF were counted under a microscope. The levels of IL-17 and TGF-beta1 in serum and BALF were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: There were no significant differences in total cell count and percentage of macrophages between the two asthma groups and the control group (P>0.05). The percentages of neutrophils, eosinophils and epithelial cells in BALF were significantly higher in the two asthma groups than in the control group (P<0.05). The two asthma groups had significantly higher levels of IL-17 and TGF-beta1 in serum and BALF than the control group (P<0.05), and the moderate or severe asthma group had significantly higher levels of IL-17 and TGF-beta1 in serum and BALF than in the mild asthma group (P<0.05). The serum levels of IL-17 and TGF-beta1 were positively correlated with those in BALF (r=0.935 and 0.943, both P<0.05). In children with asthma, serum IL-17 level was positively correlated with the percentages of neutrophils, eosinophils, and epithelial cells in BALF (r=0.802, 0.799, and 0.674, all P<0.05), and a positive correlation was also seen between serum levels of IL-17 and TGF-beta1 (r=0.878, P<0.05). CONCLUSIONS: Levels of IL-17 and TGF-beta1 in serum and BALF are elevated in children with asthma. IL-17 and TGF-beta1 may be involved in the occurrence and development of asthma, and they play important roles in asthma attack and aggravation. PMID- 26835312 TI - Epidemiological survey and analysis of asthma in children aged 0-14 years old in urban and rural areas of Chengdu region. AB - OBJECTIVES: To investigate the prevalence and incidence of asthma among children aged 0-14 years, with different living environments, economic levels, and sanitary conditions, in the urban and rural areas of Chengdu, China, and their influential factors. METHODS: Children aged 0-14 years who were selected from urban, suburban, and rural areas of Chengdu were included in the study. The subjects were selected from all children aged 0-14 years in schools, kindergartens, and communities by random, cluster and non-proportional sampling. Parents were surveyed by questionnaire to find out suspected cases, which were then confirmed by inquiry and physical examination in the departments of respiratory medicine. All the obtained data were analyzed using SPSS statistical software. RESULTS: A total of 12,082 children from the urban areas, 5,677 from suburban areas, and 5,590 from the rural areas were included in the study. Of all the subjects, 551 (4.56%) had confirmed asthma, 150 (2.64%) had cough variant asthma (CVA), and 142 (2.54%) had suspected asthma. The prevalence rate of asthma was significantly higher in the urban areas than in the suburban and rural areas. The correct rate of diagnosis of asthma and CVA was highest in the urban areas, followed by the suburban and rural areas. Use of antibiotics and systemic corticosteroids was most common in the rural areas, followed by the suburban and urban areas, but this pattern was reversed for use of inhaled corticosteroids and leukotriene modifier. All the results in the three areas demonstrated that sex, age, age at which the first attack occurred, respiratory tract infection, inhalation/intake of allergens, and genetic factors were significantly associated with asthmatic attack. CONCLUSIONS: Population density, living environment, medical and health resources and economic level are associated with the prevalence and treatment of asthma. PMID- 26835314 TI - Two separated thrombi in deep veins associated with pulmonary embolism after Mycoplasma pneumoniae infection: a case in adolescent female. AB - Mycoplasma pneumoniae is a common pathogen for respiratory infection in children, and vascular complication is one of the rarest extrapulmonary complications but with serious consequences. We report a twelve-year-old Chinese female presenting with fever, dry cough, and chest pain aggravated by respiration. She was diagnosed pneumonia due to Mycoplasma pneumoniae and treated with Azithromycin until unexpected tachypnea and swelling in the right lower limb happened. Then ultrasonic examination had revealed two separated thrombi in deep veins before pulmonary embolism was found. Finally she was cured by anticoagulation and immunosuppressive therapy. Though the mechanism of thrombosis after Mycoplasma pneumoniae infection remains unknown, the positive finding in anticardiolipin antibody as well as multi-site thromboses gives a strong hint to immune modulation. Thrombosis should be considered for those who have significantly increased C-reactive protein and positive anticardiolipin antibody after Mycoplasma pneumoniae infection. To our knowledge, this is the first report describing two unattached thrombi in deep veins associated with pulmonary embolism after Mycoplasma pneumonia infection. PMID- 26835315 TI - Professor Olle Jane Sahler: training mothers to manage cancer-related problems in children. PMID- 26835316 TI - Stage I clear cell sarcoma of the kidney: is it the time for a less intensive adjuvant treatment? AB - Clear cell sarcoma of the kidney (CCSK) is a rare type of renal tumor, comprising 2% to 5% of all primary renal tumors in children. Despite the label of "unfavorable" tumor, with recent multimodality treatment schedules, including radiotherapy and multi-agent chemotherapy, disease free survival rates approaching 80% can be achieved. Younger age at tumor diagnosis and advanced stage disease represent adverse prognostic factors. Of note, as a consequence of oncologic therapies a number of surviving patients have suffered from late sequelae on the musculoskeletal, gastrointestinal, hepatic, endocrine and cardiovascular function, or developed second tumors. Improved survival rates and a deeper knowledge of iatrogenic complications have promoted the awareness of a sequential reduction of treatment intensity, at least for low-stage CCSK, above all focusing on the abolition of flank radiation therapy (RT). It is fundamental to recognize that the rarity of this tumor calls for international cooperation trough controlled clinical trials, and without forgetting the key importance of a correct histological diagnosis and adequate surgical staging. The recent recognition of CCSK specific chromosomal translocation might help to guide targeted therapies complementary to conventional chemotherapy and radiotherapy. PMID- 26835317 TI - Preoperative chemotherapy and local stage III in nephroblastoma. AB - The evolution of Nephroblastoma (WT) treatment over the last decades has been one major success around the world. Despite pursuing different upfront treatment approaches the Children's Oncology Group (COG, former National Wilms Tumor Study Group, NWTSG) and the International Society of Paediatric Oncology's Renal Tumor Study Group (SIOP-RTSG) show the same outcome. Treatment starts with preoperative chemotherapy in SIOP-RTSG compared to initial surgery in COG. Response to chemotherapy can be used as a stratification parameter. This allows treating patients with blastemal subtype more aggressively resulting in a better event free survival (EFS). Moreover the percentage of patients with local stage III is less in SIOP-RTSG than in COG studies. Lymph node involvement, in NWTS 5 together with residual microscopic disease, results in a lower EFS in both study groups. But overall survival (OS) is not different comparing patients with or without positive lymph nodes (LN). No other reason for stage III has a significant impact on outcome. The role of radiotherapy for local tumor control in stage III is important, but the radiation dose needs to be questioned as 10.8 Gy used in COG is as efficient as 15 Gy in SIOP-RTSG protocols. In addition in part of low income countries radiotherapy can not be given due to a lack of radiation facilities. Nevertheless some patients are cured without irradiation. The analysis of local stage III patients underlines the importance of preoperative chemotherapy and the need for molecular studies to better stratify patients according to their individual risk. PMID- 26835313 TI - Distress and adjustment among adolescents and young adults with cancer: an empirical and conceptual review. AB - Adolescents and young adults (AYAs) with cancer must simultaneously navigate the challenges associated with their cancer experience, whilst striving to achieve a number of important developmental milestones at the cusp of adulthood. The disruption caused by their cancer experience at this critical life-stage is assumed to be responsible for significant distress among AYAs living with cancer. The quality and severity of psychological outcomes among AYAs remain poorly documented, however. This review examined the existing literature on psychological outcomes among AYAs living with cancer. All psychological outcomes (both distress and positive adjustment) were included, and AYAs were included across the cancer trajectory, ranging from newly-diagnosed patients, to long-term cancer survivors. Four key research questions were addressed. Section 1 answered the question, "What is the nature and prevalence of distress (and other psychological outcomes) among AYAs living with cancer?" and documented rates of clinical distress, as well as evidence for the trajectory of this distress over time. Section 2 examined the individual, cancer/treatment-related and socio demographic factors that have been identified as predictors of these outcomes in this existing literature. Section 3 examined current theoretical models relevant to explaining psychological outcomes among AYAs, including developmental models, socio-cognitive and family-systems models, stress-coping frameworks, and cognitive appraisal models (including trauma and meaning making models). The mechanisms implicated in each model were discussed, as was the existing evidence for each model. Converging evidence implicating the potential role of autobiographical memory and future thinking systems in how AYAs process and integrate their cancer experience into their current sense of self and future goals are highlighted. Finally, Section 4 addressed the future of psycho-oncology in understanding and conceptualizing psychological outcomes among AYAs living with cancer, by discussing recent empirical advancements in adjacent, non oncology fields that might improve our understanding of psychological outcomes in AYAs living with cancer. Included in these were models of memory and future thinking drawn from the broader psychology literature that identify important mechanisms involved in adjustment, as well as experimental paradigms for the study of these mechanisms within analogue, non-cancer AYA samples. PMID- 26835319 TI - High dose therapy for recurrent Wilms' tumor. AB - The prognosis for most patients with newly diagnosed Wilms' tumor (WT) is excellent, but those who have recurrent or refractory disease have a significantly worse prognosis. High dose chemotherapy (HDT) requiring autologous stem-cell rescue has been tried for recurrent WT with variable results, but no randomized clinical trial has ever been performed. A recent review by T.C. Ha and colleagues of the published cases to date suggests HDT may be beneficial to the very high risk subset of patients with recurrent WT, but this conclusion is fraught with the caveats of any retrospective review. A prospective clinical trial would be challenging to complete but with careful planning and international collaboration it could be accomplished. Such a trial is likely the only way to know with certainty the safety and efficacy of HDT for recurrent WT. PMID- 26835318 TI - Wilms' tumor: biology, diagnosis and treatment. AB - Wilms' tumor is the commonest renal tumor of childhood affecting one in 10,000 children. It is also one of the successes of paediatric oncology with long term survival above 90% for localised disease and 75% for metastatic disease. Successful management of Wilms' tumor necessitates meticulous attention to correct staging of the tumor and a collaborative effort between paediatric oncologists, specialist surgeons, radiologists, pathologists, and radiation oncologists. Although current treatment protocols are based on risk assignment to minimise toxicity for low risk patients and improve outcomes for those with high risk disease, challenges remain in identifying novel molecular, histological and clinical risk factors for stratification of treatment intensity. Knowledge about Wilms' tumor biology and treatment is evolving rapidly and remains a paradigm for multimodal malignancy treatment. Future efforts will focus on the use of biomarkers to improve risk stratification and the introduction of newer molecularly targeted therapies that will minimise toxicity and improve the outcomes for patients with unfavourable histology and recurrent disease. The aim of this article is to summarise advances in our understanding of the biology of Wilms' tumor and to describe the current approaches to clinical management of patients. PMID- 26835320 TI - Wilms tumor with intravascular tumor thrombus. AB - Wilms tumor (WT) is one of the most common solid tumors in children. It is the second most common extracranial solid tumor after neuroblastoma. WT has a strong tendency to invade blood vessels in the form of tumor thrombus, into the renal veins, and inferior vena cava and even into the right atrium. Extension of tumor thrombus along to the renal vein into the inferior vena cava occurs in 4-10% of all patients. Tumor thrombus extending to the right atrium is less reported as 0.7-1%. WT with renal vein thrombus has been reported to be more common in the right kidney because of the shorter right renal vein. Most patients with tumor thrombus are asymptomatic and diagnosis is only made on imaging investigations. Several imaging modalities including computed tomography (CT), magnetic resonance imaging (MRI) and Doppler ultrasonography (USG) can demonstrate intravascular tumor thrombus before surgery. In addition to CT and MRI, Doppler USG is reliable in demonstrating the presence and extent of inferior vena cava tumor thrombus. The management of WT with tumor thrombus is determined by multiple factors such as extent of tumor thrombus, chemotherapy response of the tumor. Now, it is generally recommended to use preoperative chemotherapy to a patient presenting with intravascular tumor thrombus. This approach is helpful to decrease the extent of the vascular thrombus which facilitates surgical excision. Most intracaval and intraatrial thrombi in WT show a response to chemotherapy. Neoadjuvant chemotherapy causes tumor regression in nearly half of the patients. Most of them can be managed without the need for cardiac bypass surgery. The decision of initial surgery or preoperative chemotherapy should be carefully determined on every case. Primary surgery would only be indicated in a patient who is unstable because of thrombus that might dislodge and cause acute symptoms. Presence of tumor thrombus in WT needs for multidisciplinary care including pediatric oncologists, pediatric surgeons, and pediatric cardiac surgeons. PMID- 26835321 TI - The management of bilateral Wilms tumor. AB - Wilms tumor (WT) is the most common malignant renal tumor in childhood. Approximately 5-7% of WT patients present with bilateral disease, either synchronously or metachronously. Bilateral WT usually occurs in younger children and more often in girls. Management of a child with bilateral WT is very challenging. In contrast to unilateral WT, there has not been uniform agreement about the therapeutic strategy in the management of bilateral WT. As surgery is a critical component in the treatment of WT, the aim is to achieve a high cure rate while maintaining adequate long-term renal function in patients with bilateral WT. In the past, radical surgical procedures which lead to the patients on dialysis have been traditionally recommended in these patients. After several multicentre trials, bilateral biopsies followed by pre-operative chemotherapy and then renal salvage surgery have been recommended. The management of bilateral WT has evolved from primary surgical extirpation to kidney-preserving resection after preoperative chemotherapy. Preoperative chemotherapy often results in significant reduction in tumor size, thereby facilitating subsequent renal salvage. The analysis of children with bilateral WT shows that preservation of renal parenchyma is possible following initial preoperative chemotherapy. Only centers with experience in bilateral WT should treat the cases with bilateral WT to provide optimal treatment. PMID- 26835322 TI - New risk classification is necessary in the treatment of Wilms tumor. AB - The National Wilms Tumor Group (NWTS) presented the clinicopathological findings predicting relapse in children with stage III favorable-histology (FH) Wilms tumor (WT) treated in the NWTS-5 study. They reported that lymph node involvement and a microscopic residual tumor were highly predictive of the EFS and OS, and concluded that patients with different stage III criteria may receive different therapies. These data suggest that the current risk classification of WT is not satisfactory. Like other pediatric tumors, such as neuroblastoma and rhabdomyosarcoma, more systemic and detailed risk classification for WT should be established using various clinical and biological markers. In the previous therapeutic protocols for WT, no biological marker was used for risk classification. Therefore, it is important to identify effective biological markers related to the prognosis of WT. The presence of LOH at 1p and 16q was associated with a worse EFS and OS, and was used for risk classification to choose the treatment regimens used in the recent COG clinical trials. There are some candidate prognostic factors that can be used in the future risk classification of WT, such as the methylation status of RASSF1A. A worldwide cooperative study should be conducted in the future to confirm whether these factors are useful in the risk classification. The goal of treatment for WT is to identify approaches that provide excellent outcomes for children with low-risk tumors without the need for chemotherapy or XRT. Conversely, more aggressive therapy may be used for children with high-risk tumors in an effort to improve their survival. To meet these goals, a new effective risk classification for WT should be established via collaborative clinical trials. PMID- 26835323 TI - Social and biological factors influencing the outcomes of children with Wilms tumors in Kenya and other Sub-Saharan countries. AB - Wilms tumor (WT) is a common pediatric solid tumor, and the 5-year event-free survival rate of patients with this tumor has reached 85-90% in developed countries, whereas those in developing countries were reported to be less than 50%. To overcome these disparities, physicians and investigators in developed and developing countries are currently performing research with the aim of the better management of children with WT in Kenya and other Sub-Saharan countries. Axt and colleagues published a study that increased understanding of clinicopathology of WT in Kenya on the basis of a comprehensive web-based WT registry. The study revealed that patients enrolled in the National Health Insurance Fund (NHIF) showed better completion rate of therapy and better event-free survival than those not enrolled, indicating insufficient health coverage for those not enrolled in the NHIF. Approximately 20-30% of Kenyan population is estimated to be covered by some forms of health insurance, mostly by the NHIF. This could be improved through various approaches. The report described that 2-year event-free survival rate was 52.7% for all patients, although loss to follow up was 50%; the findings indicate large problems both in the study results and also in the completion of treatment. It is crucial to determine at which point patients stopped their treatment and why. The development of standardized treatment protocol for WT is an urgent agenda. We hope that researchers in developed countries and health providers in Kenya can work together in future to conquer disparities in the outcomes of children with WT. PMID- 26835325 TI - The evolution of blood-spot newborn screening. AB - Over 50 years after the introduction of a blood-spot newborn screening test using the bacterial-inhibition assay (BIA), blood-spot newborn screening has evolved into complex public service scientific programmes. For several decades, many patients with phenylketonuria (PKU), congenital hypothyroidism (CH), cystic fibrosis (CF) and hemoglobinopathy disorders have benefited from early intervention across the world. In the last 20 years, there have been great changes in laboratory techniques and high-throughput data handling meaning that a huge spectrum of disorders can be identified from an increasing population. This coupled with the fact that there are an increasing number of therapies for specific rare disorders mean that health services may become inundated with complex and expensive demands in the future. Some of these issues have been realised in the implementation of multiplex assay such as electrospray tandem mass spectrometry (MSMS) programmes but will be much more exaggerated if genomic sequencing screening becomes a reality. In this context, the core-principles for implementation of newborn screening tests remain as important today as they have in the past when new tests are considered as part of the blood-spot screening programme. PMID- 26835324 TI - Phenylketonuria: translating research into novel therapies. AB - Phenylketonuria (PKU) is an inborn error of metabolism of the amino acid phenylalanine. It is an autosomal recessive disorder with a rate of incidence of 1 in 10,000 in Caucasian populations. Mutations in the phenylalanine hydroxylase (PAH) gene are the major cause of PKU, due to the loss of the catalytic activity of the enzyme product PAH. Newborn screening for PKU allows early intervention, avoiding irreparable neurological damage and intellectual disability that would arise from untreated PKU. The current primary treatment of PKU is the limitation of dietary protein intake, which in the long term may be associated with poor compliance in some cases and other health problems due to malnutrition. The only alternative therapy currently approved is the supplementation of BH4, the requisite co-factor of PAH, in the orally-available form of sapropterin dihydrochloride. This treatment is not universally available, and is only effective for a proportion (estimated 30%) of PKU patients. Research into novel therapies for PKU has taken many different approaches to address the lack of PAH activity at the core of this disorder: enzyme replacement via virus-mediated gene transfer, transplantation of donor liver and recombinant PAH protein, enzyme substitution using phenylalanine ammonia lyase (PAL) to provide an alternative pathway for the metabolism of phenylalanine, and restoration of native PAH activity using chemical chaperones and nonsense read-through agents. It is hoped that continuing efforts into these studies will translate into a significant improvement in the physical outcome, as well as quality of life, for patients with PKU. PMID- 26835327 TI - Assisted reproductive technology in China: compliance and non-compliance. AB - According to the WHO, infertility and sterility will be the third-most serious disease worldwide in the 21st century, after cancer and cardiovascular diseases. In contrast to developed countries, assisted reproductive technology (ART) were not offered in China until the mid-1980s with the first in vitro fertilization (IVF) infant born in Taiwan in 1985, then Hong Kong in 1986, and mainland China in 1988, respectively. Since those inceptions, the practice of ART in China has evoked a variety of social, cultural, political and one-child policy responses that have resulted in restrictions on the number of IVF cycles performed annually. According to recent survey, an estimate 40-50 million women and 45 million men suffered from infertility, which is estimated that more than ten million Chinese infertile couples require ART treatment. However, it has limited access to ART facilities, many of them may not have a child are whirling to all types of fertility therapies. Exposure to radiation, pesticides and other environmental pollutants, work-related stress and unhealthy lifestyles are believed to contribute to the increasing incidence of infertility in China. The aim of this first report is to provide China nationwide ART data and government policy in compliance and ?non-compliance, particularly related to family plan policy in China. PMID- 26835328 TI - Uniparental disomy in Robertsonian translocations: strategies for uniparental disomy testing. AB - Robertsonian translocations (ROBs) are whole arm rearrangements involving the acrocentric chromosomes 13-15 and 21-22 and carriers are at increased risk for aneuploidy and thus uniparental disomy (UPD). Chromosomes 14 and 15 are imprinted with expression of genes dependent on the parental origin of the chromosome. Correction of a trisomic or monosomic conceptus for chromosomes 14 or 15 would lead to one of the established UPD 14mat/pat or UPD 15 (Prader-Willi/Angelman) syndromes (PWS/AS). In view of this, prenatal UPD testing should be considered for balanced carriers of a ROB, fetuses with a familial or de novo balanced ROB that contains chromosome 14 or 15 or with a normal karyotype when a parent is a carrier of a balanced ROB with a 14 or 15. Individuals with congenital anomalies and an abnormal phenotype and carry a ROB involving the two imprinted chromosomes should also be UPD tested. PMID- 26835326 TI - Mesenchymal stem cells: potential application in intervertebral disc regeneration. AB - Chronic low back pain is one of the leading public health problems in developed countries. Degeneration of the intervertebral disc (IVD) is a major pathological process implicated in low back pain, which is characterized by cellular apoptosis and senescence with reduced synthesis of extracellular matrix (ECM). Currently, there is no clinical therapy targeting the reversal of disc degeneration. Recent advances in cellular and molecular biology have provided an exciting approach to disc regeneration that focuses on the delivery of viable cells to the degenerative disc. Adult mesenchymal stem cells (MSCs) are multipotent stem cells with self-renewal capacities and are able to differentiate into diverse specialized cell types, including chondrocyte lineages. The potential of stem cell therapy in disc degeneration is to repopulate the disc with viable cells capable of producing the ECM and restoring damaged tissue. The present literature review summarizes recent advances in basic research and clinical trials of MSCs to provide an outline of the key roles of MSCs therapies in disc repair. The review also discusses the controversies, challenges and therapeutic concepts for the future. PMID- 26835329 TI - Genetics of hereditary neurological disorders in children. AB - Hereditary neurological disorders (HNDs) are relatively common in children compared to those occurring in adulthood. Recognising clinical manifestations of HNDs is important for the selection of genetic testing, genetic testing results interpretation, and genetic consultation. Meanwhile, advances in next generation sequencing (NGS) technologies have significantly enabled the discovery of genetic causes of HNDs and also challenge paediatricians on applying genetic investigation. Combination of both clinical information and advanced technologies will enhance the genetic test yields in clinical setting. This review summarises the clinical presentations as well as genetic causes of paediatric neurological disorders in four major areas including movement disorders, neuropsychiatric disorders, neuron peripheral disorders and epilepsy. The aim of this review is to help paediatric neurologists not only to see the clinical features but also the complex genetic aspect of HNDs in order to utilise genetic investigation confidently in their clinical practice. A smooth transition from research based to clinical use of comprehensive genetic testing in HNDs in children could be foreseen in the near future while genetic testing, genetic counselling and genetic data interpretation are in place appropriately. PMID- 26835331 TI - Spectral karyotyping: an unique technique for the detection of complex genomic rearrangements in leukemia. AB - Spectral karyotyping (SKY) is a novel cytogenetic technique, has been developed to unambiguously display and identify all 24 humans chromosomes at one time without a priori knowledge of any abnormalities involved. SKY can discern the aberrations that can't be detected very well by conventional banding technique and Fluorescent in situ hybridization (FISH). So SKY is hyper accurate, hypersensitive, and hyper intuitionist. We will review the elements and application of SKY in leukemia. PMID- 26835332 TI - Advances in the medical research and clinical applications on the plasma DNA. AB - Plasma DNA has had a strong impact and influence on basic medical research and clinical practice since the discovery of low levels of plasma DNA in healthy individuals under different physiological conditions. Although the source of circulating DNA still requires further investigation, a wide range of research has also proven the value of qualitative and quantitative measurements of plasma DNA in many disease conditions. The use of plasma DNA has a biomarker is advantageous due to accessibility, reliability, reproducibility, sensitivity, specific and relatively low cost. Recently, the detection of circulating (plasma) DNA quantitative changes have been using in the studies on the tumor gene mutations and to monitor disease progressing and to predict the disease prognosis. Such technique also has been using other many different fields, particularly in prenatal diagnosis, for which plasma DNA testing is preferable due to non-invasiveness. This article reviews the research progression and clinical applications of plasma DNA in the last several years. PMID- 26835330 TI - Preterm birth and single nucleotide polymorphisms in cytokine genes. AB - Preterm birth (PTB) is an important issue in neonates because of its complications as well as high morbidity and mortality. The prevalence of PTB is approximately 12-13% in USA and 5-9% in many other developed countries. China represents 7.8% (approximately one million) of 14.9 million babies born prematurely annually worldwide. The rate of PTB is still increasing. Both genetic susceptibility and environmental factors are the major causes of PTB. Inflammation is regarded as an enabling characteristic factor of PTB. The aim of this review is to summarize the current literatures to illustrate the role of single nucleotide polymorphisms (SNPs) of cytokine genes in PTB. These polymorphisms are different among different geographic regions and different races, thus different populations may have different risk factors of PTB. SNPs affect the ability to metabolize poisonous substances and determine inflammation susceptibility, which in turn has an influence on reproduction-related risks and on delivery outcomes after exposure to environmental toxicants and pathogenic organisms. PMID- 26835333 TI - Advances and issues in flow cytometric detection of immunophenotypic changes and genomic rearrangements in acute pediatric leukemia. AB - Flow cytometry with its rapidly increasing applications has been using to aid the diagnosis of hematological disorders for more than two decades. It is also the most commonly used technology in childhood leukaemia diagnosis, characterization, prognosis prediction and even in the decision making of targeted therapy. Leukemia cells can be recognized by virtue of unique cell marker combinations, visualized with monoclonal antibodies conjugated and detected by flow cytometry. Currently, such instruments allow the detection of eight or more markers by providing a comprehensive description of the leukemic cell phenotype to facilitate their identification, especially in detecting and monitoring of minimal residual disease (MRD) during treatment. Additionally, the flow cytometric DNA index (DI) can identify biclonality at diagnosis and distinguish persistent aneuploid leukemia during induction therapy, when the standard cytogenetic and morphologic techniques fail to do so. This review focuses on the latest advances and application issues about some of flow cytometric diagnostic and prognostic applications for acute pediatric leukemia. PMID- 26835335 TI - Pediatric neurosurgery. PMID- 26835337 TI - Non-accidental trauma in pediatric patients: a review of epidemiology, pathophysiology, diagnosis and treatment. AB - Non-accidental trauma (NAT) is a leading cause of childhood traumatic injury and death in the United States. It is estimated that 1,400 children died from maltreatment in the United States in 2002 and abusive head trauma (AHT) accounted for 80% of these deaths. This review examines the epidemiology and risk factors for NAT as well as the general presentation and required medical work up of abused children. In addition, potential algorithms for recognizing cases of abuse are reviewed as well as outcomes in children with NAT and potential neurosurgical interventions which may be required. Finally, the evidence for seizure prophylaxis in this population is addressed. PMID- 26835334 TI - Advances in paediatric cancer treatment. AB - Four out of five children diagnosed with cancer can be cured with contemporary cancer therapy. This represents a dramatic improvement since 50 years ago when the cure rate of childhood cancer was <25% in the pre-chemotherapy era. Over the past ten years, while improvement in overall survival (OS) has been marginal, progress in pediatric oncology lies with adopting risk-adapted therapeutic approach. This has been made possible through identifying clinical and biologic prognostic factors with rigorous research and stratifying patients using these risk factors, and subsequently modifying therapy according to risk group assignment. This review provides a perspective for eight distinct pediatric malignancies, in which significant advances in treatment were made in the last decade and are leading to changes in standard of care. This includes four hematologic malignancies [acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL)] and four solid tumors [medulloblastoma (MB), low grade glioma (LGG), neuroblastoma (NB) and Ewing sarcoma (ES)]. Together, they comprise 60% of childhood cancer. Improved patient outcome is not limited to better survival, but encompasses reducing both short and long-term treatment-related complications which is as important as cure, given the majority of childhood cancer patients will become long-term survivors. Risk-adapted approach allows treatment intensification in the high-risk cohort while therapy can be de-escalated in the low-risk to minimize toxicity and late sequelae without compromising survival. Advances in medical research technology have also led to a rapid increase in the understanding of the genetics of childhood cancer in the last decade, facilitating identification of molecular targets that can potentially be exploited for therapeutic benefits. As we move into the era of targeted therapeutics, searching for novel agents that target specific genetic lesions becomes a major research focus. We provide an overview of seven novel agents (bevacizumab, bortezomib, vorinostat, sorafenib, tipifarnib, erlotinib and mTOR inhibitors), which have been most frequently pursued in childhood cancers in the last decade, as well as reporting the progress of clinical trials involving these agents. PMID- 26835338 TI - Hemispherectomy in the treatment of seizures: a review. AB - The term hemispherectomy refers to the complete removal or functional disconnection of a cerebral hemisphere. The technique was initially developed over 85 years ago to treat infiltrating brain tumors but is now used exclusively for medically refractory epilepsy. Hemispherectomy surgery has progressed from an extremely morbid procedure fraught with complications to a fairly routine one performed at most pediatric epilepsy centers with relatively low risk and great efficacy. The author reviews the history and evolution of hemispherectomy surgery, the relevant pathological conditions, as well as outcomes and complications. PMID- 26835336 TI - New concepts in the pathogenesis of hydrocephalus. AB - Hydrocephalus is a central nervous system disorder characterized by excessive accumulation of cerebrospinal fluid (CSF) in the ventricles of the brain. Cognitive and physical handicap can occur as a result of hydrocephalus. The disorder can present at any age as a result of a wide variety of different diseases. The pathophysiology of hydrocephalus is unclear. While circulation theory is widely accepted as a hypothesis for the development of hydrocephalus, there is a lack of adequate proof in clinical situations and in experimental settings. However, there is growing evidence that osmotic gradients are responsible for the water content of the ventricles of the brain, similar to their presence in other water permeable organs in the body. Therefore, brain disorders that results in excess macromolecules in the ventricular CSF will change the osmotic gradient and result in hydrocephalus. This review encompasses several key findings that have been noted to be important in the genesis of hydrocephalus, including but not limited to the drainage of CSF through the olfactory pathways and cervical lymphatics, the paravascular pathways and the role of venous system. We propose that as osmotic gradients play an important role in the water transport into the ventricles, the transport of osmotically active macromolecules play a critical role in the genesis of hydrocephalus. Therefore, we can view hydrocephalus as a disorder of macromolecular clearance, rather than circulation. Current evidence points to a paravascular and/or lymphatic clearance of these macromolecules out of the ventricles and the brain into the venous system. There is substantial evidence to support this theory, and further studies may help solidify the merit of this hypothesis. PMID- 26835339 TI - Permeability imaging in pediatric brain tumors. AB - While traditional computed tomography (CT) and magnetic resonance (MR) imaging illustrate the structural morphology of brain pathology, newer, dynamic imaging techniques are able to show the movement of contrast throughout the brain parenchyma and across the blood-brain barrier (BBB). These data, in combination with pharmacokinetic models, can be used to investigate BBB permeability, which has wide-ranging applications in the diagnosis and management of central nervous system (CNS) tumors in children. In the first part of this paper, we review the technical principles underlying four imaging modalities used to evaluate BBB permeability: PET, dynamic CT, dynamic T1-weighted contrast-enhanced MR imaging, and dynamic T2-weighted susceptibility contrast MR. We describe the data that can be derived from each method, provide some caveats to data interpretation, and compare the advantages and disadvantages of the different techniques. In the second part of this paper, we review the clinical applications that have been reported with permeability imaging data, including diagnosing the nature of a lesion found on imaging (neoplastic versus non-neoplastic, tumor type, tumor grade, recurrence versus pseudoprogression), predicting the natural history of a tumor, monitoring angiogenesis and tracking response to anti-angiogenic agents, optimizing chemotherapy agent selection, and aiding in the development of new antineoplastic drugs and methods to increase local delivery of chemotherapeutics. PMID- 26835340 TI - Laser induced thermal therapy (LITT) for pediatric brain tumors: case-based review. AB - Integration of Laser induced thermal therapy (LITT) to magnetic resonance imaging (MRI) have created new options for treating surgically challenging tumors in locations that would otherwise have represented an intrinsic comorbidity by the approach itself. As new applications and variations of the use are discussed, we present a case-based review of the history, development, and subsequent updates of minimally invasive MRI-guided laser interstitial thermal therapy (MRgLITT) ablation in pediatric brain tumors. PMID- 26835341 TI - Intraoperative MRI in pediatric neurosurgery-an update. AB - Since the advent of intraoperative magnetic resonance imaging (ioMRI) at the Brigham and Women's Hospital in 1994, ioMRI has spread widely and in many different forms. This article traces the developmental history of ioMRI and reviews the relevant literature regarding it's effectiveness in pediatric neurosurgery. While of considerable expense, current trends in healthcare essentially mandate the use of ioMRI in a growing number of cases. PMID- 26835342 TI - Endoscopic craniosynostosis repair. AB - INTRODUCTION: Craniosynostosis is a rare condition that affects approximately one child in every 2,000 live births, and involves pathological fusion of two or more skull bones. Consequences of craniosynostosis include possible limitation of brain growth and cosmetic effects on the appearance of the child. Traditional repairs for these conditions over the past 3-4 decades have involved an open operation with a large skin incision and major manipulations of the skull bones. More recently, minimally invasive endoscopic techniques have been developed to release the skull bones, followed by postoperative treatment with either an external orthosis or internal springs and distractors to achieve the desired correction. METHODS: In this review minimally invasive endoscopic repair will be reviewed. A general overview of the condition and techniques for correction will be discussed, followed by specific application of these surgeries for different craniosynostosis diagnoses. Attention to the subtleties of each specific condition will be highlighted. SUMMARY: Over the past two decades clinical experience and a large number of publications have substantiated the benefits of minimally invasive endoscopic techniques for the treatment of craniosynostosis. These techniques have clear benefits for selected patients, and should be part of the standard of care for this condition at craniofacial centers. PMID- 26835343 TI - Association of folate metabolism genes MTHFR and MTRR with multiple complex congenital malformation risk in Chinese population of Shanxi. AB - Birth defects are common, serious malformations with a complex etiology that suggests involvement of both genetic and environmental factors. Low dietary folate and polymorphisms in genes of folate metabolism can influence risk for birth defects. In the present study 250 Chinese birth defects cases who suffered 1-8 types of birth defect disease phenotypes were subjected and two genetic variants in two folate metabolism key enzymes, rs1801394 of methionine synthase reductase (MTRR) and rs1801133 of methylenetetrahydrofolate reductase (MTHFR) were genotyped by using SNaPshot method. The results indicated that rs1801394 and rs1801133 were associated with multiple birth defects. According to homology of organogenesis, the disease phenotypes were classified into ectoderm-, mesoderm-, and endoderm-developed groups. Genetic analysis results displayed that as protective factors, genetic variants of rs1801133 and rs1801394 were associated with the risk of ectoderm-, and endoderm-developed malformations, but only the variant of rs1801394 was associated with the risk of mesoderm-developed malformations. Our present study first related nutrition metabolism related gene variants to germ layers and provided a novel understanding of an implication of earlier causation of birth defects pathogenesis in humans. PMID- 26835344 TI - Fifteen years of routine childhood varicella vaccination in the United States strong decrease in the burden of varicella disease and no negative effects on the population level thus far. PMID- 26835345 TI - Should varicella vaccine be included in the routine immunization programme? PMID- 26835346 TI - Varicella vaccination programs do not seem to shift the age of disease to older age groups. AB - The paper of Baxter et al., recently published in Pediatrics show through five cross-sectional studies, a high impact of vaccination in the decline of varicella incidence and hospitalizations in all age groups in the United States between 1995 and 2009. As a consequence of herd immunity, varicella incidence has also diminished in those non vaccinated, which indicates no shift in the burden of varicella to older age groups. PMID- 26835347 TI - Evaluation of cerebral function in high risk term infants by using a scoring system based on aEEG. AB - OBJECTIVE: To investigate the relationship between the amplitude integrated electroencephalogram (aEEG) findings and neurodevelopmental outcomes of high-risk term infants with neurological disorders and develop a scoring system for assessment of the cerebral function. METHODS: The neurological outcome was assessed at 12- to 18-month of age by using the Bayley Scales of Infant Development II. Valuation of the classification of aEEG background pattern, epileptic electrical activity and sleep-weak cycle (SWC) was conducted to develop a new scoring system. The correlation between the summarized scores and outcome analyzed, and the predictive test of the score system was calculated. RESULTS: A total of 81 infants (39 with asphyxia, 10 with hypoglycemia, 15 with acute bacterial meningoencephalitis, 10 with hyperbilirubinemia and 7 with inborn errors of metabolism) enrolled in the study. The neurological outcome was positive correlated with the background pattern, electrical activity, SWC and summarized scores of the score system based on aEEG. The scoring system has a higher r value, specificity, PPV and lower sensitivity compared with the separate entities such as background pattern, seizures and SWC. The area under the receiver operator characteristics (ROC) curve for predicting outcome by the scoring system was 0.93 (95% CI, 0.878-0.990), with the cut-off value of 7.5. CONCLUSIONS: aEEG maybe a potential tool for monitoring cerebral function in term infants at risk for poor neurodevelopmental outcomes. Our proposed scoring system based on aEEG could quantify information provided by aEEG objectively and could be a good predictor for neurological outcome. PMID- 26835348 TI - Comparison of Doppler echocardiographic and tissue Doppler velocity data in beta thalassaemia major with high and normal NT-proBNP levels of children in the south east region of Turkey. AB - BACKGROUND: It has been reported that N-terminal pro-brain natriuretic peptide (NT-proBNP) is early biomarker of iron- induced cardiomyopathy in beta thalassemia major (beta-TM). In this study, we aimed to assess the Doppler echocardiographic, tissue Doppler velocity datas and clinical characteristics in beta-TM patients with high and normal NT-proBNP levels who have normal systolic function. MATERIAL AND METHOD: Fifty-eight beta-TM patients who were on regular transfusion in every 3-4 weeks for more than one year and 20 healthy children were included into the study. According to NT-proBNP levels, beta-TM patients are divided in two groups. Group I: the patients with high NT-proBNP levels; Group II: the patients with normal NT-proBNP levels. RESULTS: The mean serum NT-proBNP levels were significantly increased in patients with beta-TM compared to control group (P<0.05). The serum ferritin levels were ranged between 676-9,476 ng/mL (mean: 3,716+/-2,003 ng/mL) in beta-TM. No correlation was found between ferritin and NT-pro BNP in patients with beta-TM. The mean age and body surface area (BSA) were significantly low in group with high NT-proBNP compared to group with normal NT-proBNP (P<0.01). The mean heart rate, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were elevated, but not significantly in group with high NT-proBNP. Also, the mean ferritin and hemoglobin levels were decreased in this group compared to group with normal NT-proBNP, but statistically not significant. The left ventricular end diastole (LVED) diameters and left ventricular mass index (LVMI) values were found significantly decreased in group with high NT-proBNP compared to other group respectively (P<0.001, P<0,05). Right ventricular early diastolic tricuspid inflow velocity/early diastolic tissue Doppler indices (TDI) tricuspid annular velocity (RV E/E') were found increased in group with high NT-proBNP levels and difference was statistically significant (P<0.05). In addition, NT-pro BNP was found correlated with RV E/E' (r: 0.320). CONCLUSIONS: According to our result, elevated NT-proBNP level was correlated with RVE/E', but it was not associated with ferritin level. The serum NT-proBNP level may be increased as a response to increased myocardial workload and decreased hemoglobin level in patients who have an increased need for transfusion. PMID- 26835349 TI - Pediatric hepatoblastoma: diagnosis and treatment. AB - Hepatoblastoma (HBL) is the most common primary liver tumor in children, and is usually diagnosed during the first 3 years of life. Collaborative multicenter studies have led to improved diagnostic and treatment strategies. The pretreatment extent of disease (PRETEXT) staging system has become a consensus classification, and an international pathological classification system has also been developed. Clinical trials examining multimodal therapy, which consists of complete surgical resection plus liver transplantation and chemotherapy, have led to improved outcomes for children with HBL. Recently, the Children's Hepatic Tumors International Collaboration (CHIC), which includes major multicenter study groups, created a shared database that merges data on all children underwent therapy in the clinical trials of these groups until 2008. CHIC has developed a global approach to risk stratification of pediatric HBL for use in future global clinical trials. The aim of this review is to report the recent developments on the diagnosis and treatment of pediatric HBL. PMID- 26835350 TI - Fanconi anemia pathway defects in inherited and sporadic cancers. AB - Fanconi anemia (FA) is a recessive chromosomal instability syndrome. It is a hereditary disorder with defects in DNA repair characterized by progressive bone marrow failure, variable congenital malformations and predisposition to develop hematological or solid tumors. Bi-allelic gene mutations in FA cause not only the FA phenotype but also genome instability and additional mutations in their somatic cells resulting in a high predisposition to many different types of cancers. Mono-allelic mutation in FA genes increases the susceptibility to several types of cancers in a sporadic manner in non-FA patients. The strong link between cancer from bi-allelic and mono-allelic FA gene mutations has been well established. Studies have demonstrated a link between FA and cancer due to gene defects which cause the disruption of the FA pathways in a proportion of familial and sporadic cancers. The convincing evidence is that one of the FA genes, FANCD1 is identical to the well-known breast cancer susceptibility gene, BRCA2. Another three FA genes were found to be associated with genes mutated from breast cancer and other types of cancers such as prostate cancer as well. Studies on FA's biological function in genome instability maintenance, DNA damage/repair and its complex regulation pathways have become the main focus within the genetic cancer research field because of many unique features of FA. The lessons learnt from FA studies provided invaluable information towards the understanding of cancer pathogenesis to be translated into targeting cancer therapies. Studies also demonstrated that FA is a paradigm of cancer-prone inherited monogenic disease, offering insights into the pathogenesis of many types of human diseases, particularly in bone marrow failure, cancer and aging. In this review, brief FA clinical characteristics, identification of FA genes and their protein pathways, the pathogenic linking between cancers from bi-allelic and mono-allelic mutated FA genes will be discussed. PMID- 26835351 TI - Advances in genetic studies of inherited bone marrow failure syndromes and their associated malignancies. AB - The inherited bone marrow failure syndromes (IBMFS) are a rare group of heterogeneous genetic disorders characterised by bone marrow failure, commonly associated with one or more congenital anomalies found in patients which have a familiar predisposition. Genetic detection of IBMFS disease types is not only to benefit to affected patients but also of help to relatives unaffected phenotypically. Patients with IBMFS have a high risk of hematologic malignancies, commonly myelodyspastic syndrome (MDS), acute myeloid leukemia (AML) and specific types solid tumours. These malignancies may require different treatment strategies due to the underlying gene defects. Studies demonstrate that over 40 genes mutations are associated with IBMFS. Recently studies using next generation sequencing have increased our understanding of the etiology and classification of IBMFS, particularly the link between the defects and the biological mechanism leading to malignancies. PMID- 26835352 TI - Neonatal rhabdomyosarcoma: an unusual presentation. AB - Though rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the paediatric age group, its occurrence in new born is rare. Often it presents as a large mass arising from anywhere in the body, most common site being head and neck region. Here we are describing a case of neonatal embyonal RMS with multiple subcutaneous nodules. PMID- 26835353 TI - Preface to the column "Metabolism of Childhood Cancer". PMID- 26835354 TI - Lin28 and let-7 in cell metabolism and cancer. AB - Malignant cells exhibit major metabolic alterations. The regulatory gene networks that regulate metabolism and the impact of these alterations on overall cellular fitness deserve further exploration. The let-7 microRNAs and their antagonists, the Lin28 RNA-binding proteins, are well-known for controlling the timing of embryonic development. This pathway has recently been shown to regulate glucose metabolism in adult mice and to reprogram metabolism during tissue injury and repair. In addition, many lines of evidence have established that Lin28 is an oncogene that drives tumorigenesis in part by suppressing let-7. The metabolic underpinnings of this oncogenic program are just beginning to be uncovered. Here, we will review the current understanding of how Lin28 exerts regenerative and oncogenic effects through metabolic mechanisms. PMID- 26835355 TI - Energy metabolism in neurodevelopment and medulloblastoma. AB - New, less toxic therapies are needed for medulloblastoma, the most common malignant brain tumor in children. Like many cancers, medulloblastomas demonstrate metabolic patterns that are markedly different from the surrounding non-neoplastic tissue and are highly organized to support tumor growth. Key aspects of medulloblastoma metabolism, including increased lipogenesis and aerobic glycolysis are derived from the metabolic programs of neural progenitors. During neural development, Sonic Hedgehog (Shh) signaling induces lipogenesis and aerobic glycolysis in proliferating progenitors to support rapid growth. Shh regulated transcription induces specific genes, including hexokinase 2 (Hk2) and fatty acid synthase (FASN) that mediate these metabolic patterns. Medulloblastomas co-opt these developmentally-regulated patterns of metabolic gene expression for sustained tumor growth. Additionally, medulloblastomas limit protein translation through activation of eukaryotic elongation factor 2 kinase (eEF2K), to restrict energy expenditure. The activation of eEF2K reduces the need to generate ATP, enabling reduced dependence on oxidative phosphorylation and increased metabolism of glucose through aerobic glycolysis. Lipogenesis, aerobic glycolysis and restriction of protein translation operate in a network of metabolic processes that is integrated by adenosine monophosphate-activated protein kinase (AMPK) to maintain homeostasis. The homeostatic effect of AMPK has the potential to limit the impact of metabolically targeted interventions. Through combinatorial targeting of lipogenesis, glycolysis and eEF2K, however, this homeostatic effect may be overcome. We propose that combinatorial targeting of medulloblastoma metabolism may produce the synergies needed for effective anti cancer therapy. PMID- 26835357 TI - Use of computed tomography (CT) for urolithiasis in pediatric patients. AB - Numbers of annual CT examinations have been increasing incrementally each year during the last 10-20 years. Use of unenhanced CT has been increasingly used for evaluation of urolithiasis, and concerned had been raised about the risks of increased radiation exposure in pediatric patients. Sensitivities and specificity for ureteral stones on conventional CT have been reported up to 98-100%, respectively. Low dose protocols have been developed with the goal of reducing radiation dose with adequate image quality. Although the sensitivity and the specificity of CT is the highest, many can be diagnosed with combination of KUB and ultrasound. CT can be utilized in equivocal cases. Low-dose radiation CT protocols have been reported with high sensitivity and specificity and should be used in pediatric patients when a CT scan is needed. PMID- 26835358 TI - Imaging in pediatric urolithiasis-what's the best choice? AB - The incidence of urolithiasis increased dramatically during the last decades in adults as well as in children. Today, when a urinary stone is suspected, the imaging modality used most frequently is non-contrast enhanced computed tomography (NCCT). Due to the high sensitivity and specifity, NCCT is regarded as the gold standard. Its major drawback is the high dose of radiation administered with this examination. This is of special concern in children. Children with urinary stones are at high risk for multiple recurrences during their life. NCCT increases the risk for abdominal and pelvic cancer in children significantly. With respect to therapeutic success, however, conventional imaging modalities like ultrasound are not inferior and are without any harm. Therefore, ultrasound is recommended as the primary imaging technique in children by several guidelines. Nevertheless, as could be shown by Tasian et al., ultrasound was the first imaging study in only 24% of children with urolithiasis. NCCT was the modality used most frequently (63%) in the USA between 2003 and 2011. There was a wide regional variation within the USA with highest CT use in the Northwestern and Southern and lowest in the New England states. It is hypothesized that engrained practice patterns and specific local medical resources as well as a lower confidence in ultrasound with its operator dependence are potential reasons. Regarding the fact that ultrasonography is highly reliable in the diagnosis of urolithiasis and is without any harm, it is essential to make all efforts to increase the adherence to the guidelines. PMID- 26835359 TI - Initial treatment of septated parapneumonic empyema with drainage plus fibrinolytic agents is equally effective as video-assisted thoracoscopic surgery, and is suitable as first-line therapy. AB - It is thought that 0.6-2% of cases of pneumonia in children are complicated by parapneumonic empyema. The mainstay treatment options for empyema are pleural chest drainage plus fibrinolysis or video-assisted thoracoscopic surgery (VATS). Marhuenda et al. reported the results of a prospective, multicenter, clinical trial in which patients with parapneumonic empyema were randomized to either drainage plus urokinase or to VATS. That showed that the median postoperative stay, median hospital stay, and number of febrile days after treatment were not significantly different between the VATS group and the urokinase group. Only three other prospective randomized trials have been conducted with the same objective. The results in these studies had partially different among four trials. But all studies described that it is apparent that VATS is not more effective than fibrinolytic treatment. Intrapleural fibrinolytic treatment, which is much less invasive and lower inexpensive than VATS, is an effective and safe alternative to surgical treatment of complicated empyema. VATS would be reserved for patients who fail to respond to chemical/enzymatic debridement. We need additional randomized controlled trials with relevant inclusion/exclusion criteria and adequate sample sizes to determine the optimal therapy for parapneumonic-complicated empyema in children. PMID- 26835356 TI - Energy metabolism in neuroblastoma and Wilms tumor. AB - To support high proliferation, the majority of cancer cells undergo fundamental metabolic changes such as increasing their glucose uptake and shifting to glycolysis for ATP production at the expense of far more efficient mitochondrial energy production by oxidative phosphorylation (OXPHOS), which at first glance is a paradox. This phenomenon is known as the Warburg effect. However, enhanced glycolysis is necessary to provide building blocks for anabolic growth. Apart from the generation of ATP, intermediates of glycolysis serve as precursors for a variety of biosynthetic pathways essential for cell proliferation. In the last 10 15 years the field of tumor metabolism has experienced an enormous boom in interest. It is now well established that tumor suppressor genes and oncogenes often play a central role in the regulation of cellular metabolism. Therefore, they significantly contribute to the manifestation of the Warburg effect. While much attention has focused on adult solid tumors, so far there has been comparatively little effort directed at elucidation of the mechanism responsible for the Warburg effect in childhood cancers. In this review we focus on metabolic pathways in neuroblastoma (NB) and Wilms tumor (WT), the two most frequent solid tumors in children. Both tumor types show alterations of the OXPHOS system and glycolytic features. Chromosomal alterations and activation of oncogenes like MYC or inactivation of tumor suppressor genes like TP53 can in part explain the changes of energy metabolism in these cancers. The strict dependence of cancer cells on glucose metabolism is a fairly common feature among otherwise biologically diverse types of cancer. Therefore, inhibition of glycolysis or starvation of cancer cells through glucose deprivation via a high-fat low carbohydrate diet may be a promising avenue for future adjuvant therapeutic strategies. PMID- 26835362 TI - Impact of vaccination on the epidemiology of varicella. PMID- 26835361 TI - Methylenetetrahydrofolate reductase polymorphisms at 3'-untranslated region are associated with susceptibility to preterm birth. AB - BACKGROUND: Etiology and mechanism of preterm birth (PTB) is complicated. Genetic susceptibility is one of the key factors involved in the pathogenic mechanism underlying PTB. METHODS: A subset of single nucleotide polymorphisms (SNPs) selected by bioinformatics approach from 3'-untranslated region (3'-UTR) of methylenetetrahydrofolate reductase (MTHFR) gene were subjected to SNaPshot analysis in a case-control study. Three SNPs (rs45451599, rs1537515, rs1537516) were simultaneously tested in one tube, among 1,135 DNA samples including 480 PTBs and 655 term controls. RESULTS: Two perfectly correlated (r(2)=1) SNPs, rs1537515 and rs1537516, were found significantly associated with PTB susceptibility [P=0.012; OR: 0.65; 95% confidence interval (CI), 0.47-0.91]. The frequencies of the minor alleles were lower in PTB cases than in controls, which the frequencies were 0.066 in PTB cases and 0.095 in controls. G and T allele frequencies of rs1537515 were the same with rs1537516 (P=0.011; OR: 0.666; 95% CI, 0.49-0.91). Rs45451599 was not found associated with PTB (P=0.52; OR: 0.76; 95% CI, 0.33-1.74). The 18-25 nucleotides in length of microRNAs (miRNAs) which can regulate gene expressions are involved in binding partial complementary sequences within 3'-UTR. The two loci are at 3'-UTR of MTHFR mRNA. Rs1537516 is a potential target of miR-1304-3p, while rs1537515 is miR-1224-3p and miR-3150-5p. CONCLUSIONS: In conclusion, rs1537515 and rs1537516 within the 3'-UTR of the MTHFR gene may be associated with susceptibility to PTB. PMID- 26835360 TI - Visuoperceptual sequelae in children with hemophilia and intracranial hemorrhage. AB - BACKGROUND: The goal of this study was to examine the impact of focal brain injuries on the outcomes of visual perception and visuospatial abilities in Mexican children with hemophilia who have experienced intracranial hemorrhages. METHODS: We assessed ten boys who had hemophilia with intracranial hemorrhage (HIC), six boys who had hemophilia without intracranial hemorrhage (HH), and ten boys without hemophilia (CTL). The Verbal (VIQ), Performance IQs (PIQ), and Full Scale IQs (FSIQ) from the Wechsler Intelligence Scale for Children-Mexican Revision, Visual Perception, and Visuospatial Abilities domains, which are from a neuropsychological assessment battery for Spanish-speaking children (ENI), were employed for our analysis. RESULTS: The results showed that the HIC group performed in the low-average range on the PIQ and FSIQ, which was lower than the HH group. The HIC group showed low performance on visual perception tests, such as line orientation, fragmented objects, and overlapping figures, compared with their matched controls. CONCLUSIONS: The results suggest that it is not the ability to recognize objects that is impaired in the HIC group, but the ability to identify objects under less favorable conditions. Our findings may have therapeutic and rehabilitative implications for the management of children with hemophilia and early focal brain lesions. PMID- 26835363 TI - Genetic causes of cancer predisposition in children and adolescents. AB - The acquisition of de novo somatic mutations accounts for approximately 90% of all new cancer diagnoses, while the remaining 10% is due to inherited genetic traits. In this latter category, individuals harbouring germline mutations show a higher likelihood of developing potentially life-threatening cancers, often at a very young age. The study of cancer genetics has profoundly helped our understanding of cancer biology, leading to better characterised malignancies, tailored targeted therapies and the identification of individuals at high risk of cancer diagnosis. This review will discuss examples of cancer syndromes in children, adolescents and young adults, the main underlying gene mutations, and the use of genetic testing to identify gene mutation carriers. Finally, we will describe how gene mutation detection is employed for the life-long management of patients with high susceptibility to cancer, including genetic counselling, increased surveillance, early intervention and use of targeted therapies. PMID- 26835364 TI - Down syndrome and leukemia: insights into leukemogenesis and translational targets. AB - Children with Down syndrome (DS) have a significantly increased risk of childhood leukemia, in particular acute megakaryoblastic leukemia (AMKL) and acute lymphoblastic leukemia (DS-ALL). A pre-leukemia, called transient myeloproliferative disorder (TMD), characterised by a GATA binding protein 1 (GATA1) mutation, affects up to 30% of newborns with DS. In most cases, the pre leukemia regresses spontaneously, however one-quarter of these children will go on to develop AMKL or myelodysplastic syndrome (MDS) . AMKL and MDS occurring in young children with DS and a GATA1 somatic mutation are collectively termed myeloid leukemia of Down syndrome (ML-DS). This model represents an important multi-step process of leukemogenesis, and further study is required to identify therapeutic targets to potentially prevent development of leukemia. DS-ALL is a high-risk leukemia and mutations in the JAK-STAT pathway are frequently observed. JAK inhibitors may improve outcome for this type of leukemia. Genetic and epigenetic studies have revealed likely candidate drivers involved in development of ML-DS and DS-ALL. Overall this review aims to identify potential impacts of new research on how we manage children with DS, pre-leukemia and leukemia. PMID- 26835366 TI - Genomic diversity in myeloproliferative neoplasms: focus on myelofibrosis. AB - The classical myeloproliferative neoplasms (MPNs) are a group of clonal diseases comprising essential thrombocythaemia (ET), polycythaemia vera (PV) and primary myelofibrosis (PMF). PMF is the rarest disease sub type and has been challenging to address due to the lack of a specific genetic marker, inadequate risk identification models and a highly variable clinical course. Continuous efforts have over time, seen the inclusion of cytogenetic information in prognostic scoring models that have resulted in improved risk stratification models providing further rationale for therapeutic management. Technological advances using single nucleotide polymorphism arrays increased the detection of known and novel MPN related changes and variant detection by massively parallel sequencing provided a large scale screening tool for the multitude of somatic gene mutations that have more recently been described in MPN. Some of these mutations show an association with specific cytogenetic changes or phenotypes. While PMF occurs mainly in adults, it has also been described in paediatric cases and shows distinct histopathological, genetic and clinical features in comparison. This review provides an overview of the genomics landscape of PMF and current developments in MPN therapy. PMID- 26835365 TI - Spanning the genomics era: the vital role of a single institution biorepository for childhood cancer research over a decade. AB - The 'genomics era' is considered to have begun with the commencement of the Human Genome Project. As translational genomic studies can only be established when human tissue samples are available for analysis, biospecimens are now proven to be an essential element for their success. During the genomics era the necessity for more extensive biobanking infrastructure has been highlighted. With the increased number of genomic studies into cancer, it is considered that the availability of biospecimens will become the rate limiting step. Despite the efforts in international biobanking, translational genomics is hampered when there low numbers of biospecimens for a particular rare diseases and is most apparent for paediatric cancer. As there is a call for biobanking practice to be responsive to the current experimental needs of the time and for more expansive systems of tissue procurement to be established we have asked the question what role does a single institution biorepository play in the current highly networked world of translational genomics. Here we describe such a case. The Tumour Bank at The Children's Hospital at Westmead (TB-CHW) in the western suburbs of Sydney was formally established in 1998 as a key resource for translational paediatric cancer research. During the genomics era, we show that the TB-CHW has developed into a key biospecimen repository for the cancer research community, during which time it has increasingly found itself having a vital role in the establishment of translational genomics for paediatric cancer. Here we detail metrics that demonstrate how as a single institution biorepository, the TB-CHW has been a strong participant in the advancement of translational genomics throughout the genomics era. This paper describes the significant contribution of a single institutional hospital embedded tumour biobank to the genomic research community. Despite the increased stringencies placed on biobanking practice, the TB-CHW has shown that a single institution biorespository can have a consistent and effective contribution to translational research into rare paediatric malignancy demonstrating its long term benefit throughout the genomics era. PMID- 26835367 TI - Emerging technologies in paediatric leukaemia. AB - Genetic changes, in particular chromosomal aberrations, are a hallmark of acute lymphoblastic lymphoma (ALL) and accurate detection of them is important in ensuring assignment to the appropriate drug protocol. Our ability to detect these genetic changes has been somewhat limited in the past due to the necessity to analyse mitotically active cells by conventional G-banded metaphase analysis and by mutational analysis of individual genes. Advances in technology include high resolution, microarray-based techniques that permit examination of the whole genome. Here we will review the current available methodology and discuss how the technology is being integrated into the diagnostic setting. PMID- 26835370 TI - Autosomal ring chromosomes in human genetic disorders. AB - Ring chromosomes arise following breakage and rejoining in both chromosome arms. They are heterogeneous with variable size and genetic content and can originate from any chromosome. Phenotypes associated with ring chromosomes are highly variable as apart from any deletion caused by ring formation, imbalances from ring instability can also occur. Of interest is ring chromosome 20 which has a significant association with epilepsy with seizure onset in early childhood. Severe growth deficiency without major malformations is a common finding in the ring chromosome carrier. This phenotype associated with ring behaviour and mitotic instability and independent of the chromosome involved has been termed the "ring syndrome". Precise genotype-phenotype correlations for ring chromosomes may not be possible as influencing factors vary depending on the extent of deletion in ring formation, ring instability and the level of mosaicism. Although ring chromosomes usually arise as de novo events, familial transmission of rings from carrier to offspring has been described and prenatal diagnosis for any pregnancies should always be considered. PMID- 26835371 TI - Genetics of monoamine neurotransmitter disorders. AB - The monoamine neurotransmitter disorders are a heterogeneous group of inherited neurological disorders involving defects in the metabolism of dopamine, norepinephrine, epinephrine and serotonin. The inheritance of these disorders is mostly autosomal recessive. The neurological symptoms are primarily attributable to cerebral deficiency of dopamine, serotonin or both. The clinical presentations were highly variable and substantial overlaps exist. Evidently, laboratory investigations are crucial for accurate diagnosis. Measurement of neurotransmitter metabolites in cerebral spinal fluid (CSF) is the key to delineate the metabolic defects. Adjuvant investigations including plasma phenylalanine, urine pterins, urine 3-O-methyldopa (3-OMD) and serum prolactin are also helpful to establish the diagnosis. Genetic analyses are pivotally important to confirm the diagnosis which allows specific treatments, proper genetic counselling, prognosis prediction, assessment of recurrent risk in the family as well as prenatal diagnosis. Early diagnosis with appropriate treatment is associated with remarkable response and favourable clinical outcome in several disorders in this group. PMID- 26835368 TI - Somatic DNA mutation analysis in targeted therapy of solid tumours. AB - Cancer is a disease of the genome with diverse aetiologies including the accumulation of acquired mutations throughout the genome. There has been a flood of knowledge improving our understanding of the biology and molecular genetics of melanoma, lung and colorectal cancer since the genomics era started. Translation of this knowledge into a better understanding of cell proliferation, survival and apoptosis has produced a paradigm shift in medical oncology enabling gene-based cancer treatment (called personalised or precision medicine). Somatic mutation analysis is crucial for a genomics approach since it can identify driver mutations-the "Achilles' heel" of cancer, and support clinical decision-making through targeted therapy. Nevertheless, the applications of somatic DNA testing in cancer face many challenges such as obtaining comprehensive coverage of the cancer genome with limited DNA being available, and delivering an accurate report in a timely fashion without false-negative and false-positive results. Further advances in DNA technologies and bioinformatics will overcome these issues and maximise opportunities for targeted therapy. Somatic mutation analysis will then become an integral part of cancer management for all malignancies. PMID- 26835372 TI - Molecular genetic studies of complete hydatidiform moles. AB - Complete hydatidiform moles (CHM) are abnormal pregnancies with no fetal development resulting from having two paternal genomes with no maternal contribution. It is important to distinguish CHM from partial hydatidiform moles, and non-molar abortuses, due to the increased risk of gestational trophoblastic neoplasia. We evaluated a series of products of conception (POC) (n=643) investigated by genome-wide microarray comparative genomic hybridisation (CGH) with the aim of refining our strategy for the identification of complete moles. Among 32 suspected molar pregnancies investigated by STR genotyping to supplement microarray CGH testing, we found 31.3% (10/32) CHM; all identified among 3.6% (10/272) early first trimester POC. We suggest that when using microarray CGH that genotyping using targeted STR analysis should be performed for all POC referrals to aid in the identification of CHM. PMID- 26835374 TI - Have we really decreased mortality due to severe burn injury in children? AB - In developed countries, in the twenty-first century, severe, large total body surface area (TBSA) burn injuries in children are rare. Prevention campaigns, education and public health interventions have significantly decreased the number of children sustaining burn injuries as well as the severity of such injuries. Many technological medical and surgical advances have been developed in burn care over the past several decades, increasing survival. Despite these interventions, long-term survival post burn injury may still be significantly reduced. PMID- 26835373 TI - 1(st) trimester miscarriage: four decades of study. AB - Miscarriage is a very common occurrence in humans. This paper sets out to present published data on research that has provided increased understanding of pregnancy failure. Clarification of definitions, exploring the range of failures from preclinical to later pregnancy losses, and the scientific tools employed to find information on the losses have been documented. What is now understood, which tools work best, and the associated limitations are all discussed. Early studies used cytogenetic methods and tissue culture to obtain results. Improvements in laboratory tools such as better tissue culture incubators, inverted microscopes, laminar flow hoods, improvements in culture media, all contributed to obtaining more results for patients. These studies demonstrated the significant contribution of unbalanced chromosomal karyotypes to pregnancy failure. Maternal age as a contributing factor in trisomy was clearly demonstrated. First trimester miscarriage exhibits very high cytogenetic abnormality; in contrast to very low rates in later losses. Combining data across all time periods of pregnancy will affect the significance of chromosomal error in the early pregnancy failures. Cytogenetic methods investigate whole genomes, and are considered to represent the standard against which new methods must be validated. New molecular genetic methods provide the opportunity to examine samples without the necessity of tissue culture. Techniques may be site-specific or whole genome. Fluorescent in situ hybridisation (FISH), comparative genomic hybridisation (CGH), array-based CGH, single nucleotide polymorphism (SNP) detection, quantitative polymerase chain reaction (qPCR), and quantitative fluorescent PCR (QF-PCR), have all been utilised. In comparison studies with classical/conventional cytogenetics, each newer method offers advantages and limitations. At the present time, a combined approach using conventional and molecular methods will elucidate the cause of miscarriage for almost all samples. In a clinical setting this would be optimum. PMID- 26835375 TI - Long term mortality in burned children. AB - Studies about risk factors for mortality in burn children are scarce and are even less in the follow up of this population across time. Usually, after complete event attendance, children are not follow-up as risk patients, burn injury affects all facets of life. Integration of professionals from different disciplines has enabled burn centers to develop collaborative methods of assessing the quality of care delivered to patients with burns. In this editorial we comment the paper of Duke et al. The authors highlight the importance of maintaining a long-term monitoring of children who suffered burns. The importance of this original study is to promote the reconsideration of clinical guides of long-term follow-up of burn patients. PMID- 26835377 TI - Rheumatic heart disease screening by "point-of-care" echocardiography: an acceptable alternative in resource limited settings? AB - Rheumatic heart disease (RHD) is estimated to affect over 20 million people worldwide, the vast majority being in developing countries. Screening for RHD has been recommended by World Health Organization (WHO) since 2004. Conventionally, auscultation has been used for diagnosing RHD. Auscultation has its limitations and may not detect mild cases. With the evolution of portable echocardiographic systems, mass screening for subclinical RHD has become possible. Portable echo has the advantage of rapid access and hence screening in schools or communities is possible. Its cost is lower than that of standard echo equipment. A large number of studies have reported echocardiographic screening for RHD over the last decade or so. A 3-10 fold increase in prevalence of RHD has been detected by using portable echo when compared with conventional method of auscultation. More recently, a small, compact, easy to carry in a pocket, hand held system has been introduced which is much cheaper than the conventional portable system. A few previous reports have shown the feasibility of using hand held echo system for diagnosis of various cardiac diseases. A recently published article has shown that the hand held system can be used to screen for RHD. It is more sensitive than the conventional auscultation for RHD. Authors of this report have concluded that screening with the hand held device may be a more cost effective strategy for screening for RHD in resource limited settings, since it is much cheaper than the portable echocardiography equipment. PMID- 26835376 TI - Echocardiographic screening for rheumatic heart disease-some answers, but questions remain. AB - Despite being preventable, rheumatic heart disease (RHD) remains a significant global cause of cardiovascular disease. Echocardiographic screening for early detection of RHD has the potential to enable timely commencement of treatment (secondary prophylaxis) to halt progression to severe valvular disease. However, a number of issues remain to be addressed regarding its feasibility. The natural history of Definite RHD without a prior history of acute rheumatic fever (ARF) and Borderline RHD are both unclear. Even if they are variants of RHD it is not known whether secondary antibiotic prophylaxis will prevent disease progression as it does in "traditionally" diagnosed RHD. False positives can also have a detrimental impact on individuals and their families as well as place substantial burdens on health care systems. Recent research suggests that handheld echocardiography (HAND) may offer a cheaper and more convenient alternative to standard portable echocardiography (STAND) in RHD screening. However, while HAND is sensitive for the detection of Definite RHD, it is less sensitive for Borderline RHD and is relatively poor at detecting mitral stenosis (MS). Given its attendant limited specificity, potential cases detected with HAND would require re-examination by standard echocardiography. For now, echocardiographic screening for RHD should remain a subject of research rather than routine health care. PMID- 26835378 TI - The case of late preterm birth: sliding forwards the critical window for cognitive outcome risk. AB - Many survivors of preterm birth experience neurodevelopmental disabilities, such as cerebral palsy, visual and hearing problems. However, even in the absence of major neurological complications, premature babies show significant neuropsychological and behavioural deficits during childhood and beyond. While the clinical tools routinely used to assess neurocognitive development in those infants have been useful in detecting major clinical complications in early infancy, they have not been equally sensitive in identifying subtle cognitive impairments emerging during childhood. These methodological concerns become even more relevant when considering the case of late preterm children (born between 34 and 36 gestational weeks). Although these children have been traditionally considered as having similar risks for developmental problems as neonates born at term, a recent line of research has provided growing evidence that even late preterm children display altered structural and functional brain maturation, with potential life-long implications for neurocognitive functioning. A recent study by Heinonen put forward the hypothesis that environmental factors, in this case educational attainment, could moderate the association between late preterm birth (LPT) and neuropsychological impairments commonly associated with aging. In this paper we bring together clinical literature and recent neuroimaging evidence in order to provide two different but complementary approaches for a better understanding of the "nature-nurture" interplay underlying the lifespan neurocognitive development of preterm babies. PMID- 26835369 TI - Retinal dystrophies, genomic applications in diagnosis and prospects for therapy. AB - Retinal dystrophies (RDs) are degenerative diseases of the retina which have marked clinical and genetic heterogeneity. Common presentations among these disorders include night or colour blindness, tunnel vision and subsequent progression to complete blindness. The known causative disease genes have a variety of developmental and functional roles with mutations in more than 120 genes shown to be responsible for the phenotypes. In addition, mutations within the same gene have been shown to cause different disease phenotypes, even amongst affected individuals within the same family highlighting further levels of complexity. The known disease genes encode proteins involved in retinal cellular structures, phototransduction, the visual cycle, and photoreceptor structure or gene regulation. This review aims to demonstrate the high degree of genetic complexity in both the causative disease genes and their associated phenotypes, highlighting the more common clinical manifestation of retinitis pigmentosa (RP). The review also provides insight to recent advances in genomic molecular diagnosis and gene and cell-based therapies for the RDs. PMID- 26835379 TI - Expression of Wilms tumor gene in high risk neuroblastoma: complementary marker to tyrosine hydroxylase for detection of minimal residual disease. AB - BACKGROUND: Neuroblastoma (NB) is an enigmatic tumor that often presents with metastatic disease at diagnosis and it is this aggressive propensity which places it among the deadliest pediatric tumors despite intensive multimodal therapy including hematopoietic stem cell transplantation (HSCT). We have previously demonstrated that Wilms tumor 1 gene (WT1) is a surrogate marker of proliferation in leukemia. To determine the potential association between WT1 and a known marker of NB, tyrosine hydroxylase (TH) in this high risk group of patients. METHODS: A total of 141 random samples from 34 patients were obtained, at diagnosis (n=27), during therapy (n=95), in clinical remission (n=13), and at the time of relapse (n=6). Quantitative RT-PCR was used for the evaluation of the level of gene expression using specific primers. RESULTS: Although similar gene expressions were demonstrated in both controls when evaluating both genes, significant difference was found at each clinical time point. Furthermore, when comparing patient samples from diagnosis to clinical remission and diagnosis to clinical relapse, individual gene expression varied. WT1 demonstrated significance (P=0.0002) and insignificance (P=0.06) whereas TH remained non significant (P=0.2, P=0.09) respectively. CONCLUSIONS: WT1 gene is indicative of cellular proliferation in NB and for this reason it can be adjuvant to TH for the detection minimal residual disease (MRD). PMID- 26835381 TI - Challenges and opportunities in the studies on rare diseases. PMID- 26835380 TI - Translational development of difluoromethylornithine (DFMO) for the treatment of neuroblastoma. AB - Neuroblastoma is a childhood tumor in which MYC oncogenes are commonly activated to drive tumor progression. Survival for children with high-risk neuroblastoma remains poor despite treatment that incorporates high-dose chemotherapy, stem cell support, surgery, radiation therapy and immunotherapy. More effective and less toxic treatments are sought and one approach under clinical development involves re-purposing the anti-protozoan drug difluoromethylornithine (DFMO; Eflornithine) as a neuroblastoma therapeutic. DFMO is an irreversible inhibitor of ornithine decarboxylase (Odc), a MYC target gene, bona fide oncogene, and the rate-limiting enzyme in polyamine synthesis. DFMO is approved for the treatment of Trypanosoma brucei gambiense encephalitis ("African sleeping sickness") since polyamines are essential for the proliferation of these protozoa. However, polyamines are also critical for mammalian cell proliferation and the finding that MYC coordinately regulates all aspects of polyamine metabolism suggests polyamines may be required to support cancer promotion by MYC. Pre-emptive blockade of polyamine synthesis is sufficient to block tumor initiation in an otherwise fully penetrant transgenic mouse model of neuroblastoma driven by MYCN, underscoring the necessity of polyamines in this process. Moreover, polyamine depletion regimens exert potent anti-tumor activity in pre-clinical models of established neuroblastoma as well, in combination with numerous chemotherapeutic agents and even in tumors with unfavorable genetic features such as MYCN, ALK or TP53 mutation. This has led to the testing of DFMO in clinical trials for children with neuroblastoma. Current trial designs include testing lower dose DFMO alone (2,000 mg/m(2)/day) starting at the completion of standard therapy, or higher doses combined with chemotherapy (up to 9,000 mg/m(2)/day) for patients with relapsed disease that has progressed. In this review we will discuss important considerations for the future design of DFMO-based clinical trials for neuroblastoma, focusing on the need to better define the principal mechanisms of anti-tumor activity for polyamine depletion regimens. Putative DFMO activities that are both cancer cell intrinsic (targeting the principal oncogenic driver, MYC) and cancer cell extrinsic (altering the tumor microenvironment to support anti-tumor immunity) will be discussed. Understanding the mechanisms of DFMO activity are critical in determining how it might be best leveraged in upcoming clinical trials. This mechanistic approach also provides a platform by which iterative pre-clinical testing using translational tumor models may complement our clinical approaches. PMID- 26835383 TI - Childhood burn injury-impacts beyond discharge. PMID- 26835382 TI - Investigation and management of the hepatic glycogen storage diseases. AB - The glycogen storage diseases (GSD) comprise a group of disorders that involve the disruption of metabolism of glycogen. Glycogen is stored in various organs including skeletal muscle, the kidneys and liver. The liver stores glycogen to supply the rest of the body with glucose when required. Therefore, disruption of this process can lead to hypoglycaemia. If glycogen is not broken down effectively, this can lead to hepatomegaly. Glycogen synthase deficiency leads to impaired glycogen synthesis and consequently the liver is small. Glycogen brancher deficiency can lead to abnormal glycogen being stored in the liver leading to a quite different disorder of progressive liver dysfunction. Understanding the physiology of GSD I, III, VI and IX guides dietary treatments and the provision of appropriate amounts and types of carbohydrates. There has been recent re-emergence in the literature of the use of ketones in therapy, either in the form of the salt D,L-3-hydroxybutyrate or medium chain triglyceride (MCT). High protein diets have also been advocated. Alternative waxy maize based starches seem to show promising early data of efficacy. There are many complications of each of these disorders and they need to be prospectively surveyed and managed. Liver and kidney transplantation is still indicated in severe refractory disease. PMID- 26835385 TI - Response to Godown and Beaton-Handheld echocardiography: A new tool for rheumatic heart disease in the developing world? PMID- 26835384 TI - Handheld echocardiography: a new tool for rheumatic heart disease screening in the developing world? PMID- 26835386 TI - Rheumatic heart disease screening in resource limited settings: is hand held device the answer? PMID- 26835387 TI - Updates in the medical management of pediatric epilepsy. PMID- 26835388 TI - Management of infantile spasms. AB - West syndrome, or infantile spasms syndrome is a frequently catastrophic infantile epileptic encephalopathy with a variety of etiologies. Despite the heterogeneous nature of causes of infantile spasms, a careful diagnostic evaluation can lead to diagnosis in many patients and may guide treatment choices. Magnetic resonance imaging (MRI) brain remains the highest yield initial study in determining the etiology in infantile spasms. Treatment of infantile spasms has little class I data, but adrenocorticotropic hormone (ACTH), prednisolone and vigabatrin have the best evidence as first-line medications. Other therapies including the ketogenic diet and other anti-epileptics medications may also prove useful in the treatment of infantile spasms. In general, more studies are needed to determine the best treatment regimen for this condition. Prognosis is generally poor, with the majority of patients having some or profound neurocognitive delays. Patients without delays at diagnosis and without an identifiable etiology, if treated appropriately, have the greatest likelihood of a normal outcome. PMID- 26835389 TI - Cannabinoids for pediatric epilepsy? Up in smoke or real science? AB - Public interest in the use of "medical marijuana" for the treatment of childhood epilepsy has burgeoned in the last few years. This has occurred in parallel with a growing interest in "medical marijuana" in general. Physicians and pediatricians must balance their patients' desire for immediate access to these products with the tenets of evidence-based medicine. This review discusses the biochemistry of cannabis products (the phytocannabinoids) setting this in the context of the endogenous endocannabinoid system. The differing and potentially modulating effects of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are reviewed. The evidence-base supporting or not the use of cannabis products for the treatment of neurological disease and specifically epilepsy is explored. The potential for adverse effects and particularly of neurotoxicity is addressed. Finally, public health and sociocultural implications are touched upon. Specific recommendations for interested physicians are provided including advocacy for patients and for a change in the "scheduling" of cannabis in order to better foster much-needed high-quality scientific research in this important area. PMID- 26835390 TI - Continuous electroencephalogram detection of non-convulsive seizures in the pediatric intensive care unit: review of the utility and impact on management and outcomes. AB - Non-convulsive seizures (NCS) are common among critically ill children with acute encephalopathy. Continuous electroencephalogram (CEEG) monitoring is an indispensable tool to detect NCS, which is essential to guiding management and assessing prognosis. Risk factors for NCS are highest in pediatric intensive care unit (PICU) patients with altered mental status (AMS) and a recently witnessed clinical seizure, acute changes on neuroimaging, and/or interictal abnormalities on CEEG. Screening for at least 24 hours in at risk pediatric populations is ideal, but around half of NCS may be detected within the first hour. Rapid treatment of prolonged seizures or status epilepticus is critical, as higher seizure burdens have been associated with poorer outcomes in critically ill children. This review integrates current information on critically ill children with AMS and the use of CEEGs, risk factors for NCS, duration of CEEG monitoring, and how the detection of NCS impacts management and outcomes. PMID- 26835391 TI - Liver tumors in children with metabolic disorders. AB - Hepatic neoplasia is a rare but serious complication of metabolic diseases in children. The risk of developing neoplasia, the age at onset, and the measures to prevent it differ in the various diseases. We review the most common metabolic disorders that are associated with a heightened risk of developing hepatocellular neoplasms, with a special emphasis on reviewing recent advances in the molecular pathogenesis of the disorders and pre-clinical therapeutic options. The cellular and genetic pathways driving carcinogenesis are poorly understood, but best understood in tyrosinemia. PMID- 26835393 TI - Where will genetic research take us? PMID- 26835394 TI - Bringing attention into higher focus within the traumatic brain injury research agenda. PMID- 26835395 TI - Mozart's music in children with epilepsy. AB - Coppola et al. reported 5 out of 11 patients suffering from drug-resistant epileptic encephalopathy associated with cerebral palsy had a >=50% reduction in the total number of seizures after listening a set of Mozart's compositions 2 h per day for 15 days. Our previous studies also revealed that both seizure frequencies, recurrence of first unprovoked seizure, and epileptiform discharges are significant reduced after listening to Mozart K.448. Until now, the real mechanism of music effect on epilepsy is still unclear. In this article, in addition to showing the beneficial effects of music on seizure, and epileptiform discharges, we are going to discuss the possible mechanism of music. The possible mechanisms include dopaminergic pathways, mirror neurons, and parasympathetic activation after listening to music. PMID- 26835392 TI - Phenylketonuria: a review of current and future treatments. AB - Phenylketonuria (PKU) is an autosomal recessive inborn error of metabolism caused by a deficiency in the hepatic enzyme phenylalanine hydroxylase (PAH). If left untreated, the main clinical feature is intellectual disability. Treatment, which includes a low Phe diet supplemented with amino acid formulas, commences soon after diagnosis within the first weeks of life. Although dietary treatment has been successful in preventing intellectual disability in early treated PKU patients, there are major issues with dietary compliance due to palatability of the diet. Other potential issues associated with dietary therapy include nutritional deficiencies especially vitamin D and B12. Suboptimal outcomes in cognitive and executive functioning have been reported in patients who adhere poorly to dietary therapy. There have been continuous attempts at improving the quality of medical foods including their palatability. Advances in dietary therapy such as the use of large neutral amino acids (LNAA) and glycomacropeptides (GMP; found within the whey fraction of bovine milk) have been explored. Gene therapy and enzyme replacement or substitution therapy have yielded more promising data in the recent years. In this review the current and possible future treatments for PKU are discussed. PMID- 26835397 TI - Clinical and financial impact of HACs: a commentary on clinical and financial costs of hospital-acquired conditions. PMID- 26835396 TI - Autoimmune encephalitis following haematopoietic stem cell transplant: a new clinical entity or a previously unrecognised one? PMID- 26835398 TI - Chronic hepatitis B in children in the United States and Canada: international origins place the disease burden on children even in the era of universal vaccination. PMID- 26835399 TI - The impact of molecular analysis on the survival of children with embryonal tumors. AB - Embryonal tumors represent a heterogeneous group of malignancies characterized by poorly differentiated cells and generally aggressive behavior. Although advances in survival rates have been made in several of these tumor types, including Wilms' tumor, retinoblastoma, and medulloblastoma, survival of patients with central nervous system (CNS) embryonal tumors, including primitive neuro ectodermal tumors (PNETs) and atypical teratoid rhabdoid tumors (AT/RT), are particularly poor. Advancing molecular analysis techniques and the development of gene expression profiles has led to the formulation of different subdivisions within many of the umbrella CNS tumor groups with clinical and prognostic implications. Some subgroups have been identified as having improved survivorships, likely not captured by large scale population data given their small numbers and relatively recent characterization. Importantly, identification of differing molecular pathways has begun to result in targeted therapies which may pave the way for even more surviving patients in the coming years. PMID- 26835400 TI - Evaluating the epilepsy and oncological outcomes of pediatric brain tumors causing seizures. PMID- 26835401 TI - Bringing attention to a need for a standardized treatment and weaning protocol for neonatal abstinence syndrome. PMID- 26835402 TI - Verbal autopsy and therapeutic itinerary of children who die before arrival in a paediatric centre in Yaounde, Cameroon. AB - BACKGROUND: In Cameroon the rate of infant-juvenile mortality remains high and most death occur in the community. Mortality statistics is usually based on hospital data which are generally insufficient and less reliable. In a context where legislation on death registration is not applied, and where conventional autopsy is not often done, verbal autopsy (VA) provides information on mortality. This study tried to experiment this method and also analyses the therapeutic pathway of a group of children who died before arrival at the emergency department of a pediatric hospital. METHODS: A cross sectional descriptive study was carried out on children who died before arrival, at the Mother and Child Centre of the Chantal Biya Foundation in Yaounde, between October 2013 and April 2014. The addresses of parents or relatives of the deceased children were registered at the start of the study. Each respondent was interviewed 5 to 6 weeks later at the residence of the deceased child, with the aid of a VA questionnaire. Information obtained was on the socio-demographic characteristics of the families, past history of deceased, clinical presentation and the different health care services sought before the death. RESULTS: In all, 40 children who died were included in the study. The majority of the deceased children were less than 5 years (82.5%) with 50.0% being less than 1 year of age. Almost half of them (47.5%) had been ill for more than 24 hours, 40% for more than 3 days. Up to 50.0% had not been taken to a health facility. Most of them had visited 2 or 3 other health facilities before dying on the way to our hospital. Auto medication was frequent (42.5%); parents initially recourse to drugs which were either bought or obtained from home. Some parents (25.0%) brought their children only after they had been to a private dispensary, or a traditional healer (15.0%). Only 7.5% benefited from consultation in a public health facility and 2.5% resorted to prayers and incantations. Whatever the kind of care sought, the choice was mostly guided by its proximity (32.5%), advice from a relative (27.5%) or its affordability. CONCLUSIONS: It is of crucial importance that the government reinforces the measures to avoid the existence of clandestine health centres and check the competence of health care professionals. Improving referral/counter referral system will permit the limitation of fatal medical errors. PMID- 26835403 TI - Premature death of children aged 2 months to 5 years: the case of the Mother and Child Center of the Chantal Biya Foundation, Yaounde, Cameroon. AB - BACKGROUND: In hospital premature deaths of children less than 5 years of age admitted for different reasons still remains very high in our context warranting study in order to reverse the tendency (using appropriate means). Our study was aimed at describing and analyzing cases of those children aged from 2 months to 5 years who died within the first 48 hours of their admission at the Mother and Child Center of the Chantal Biya Foundation (MCC/CBF). METHODS: It was a retrospective descriptive study. Data were extracted from the clinical records of the patients admitted from 2008 to 2012. Cases of accidental trauma were excluded from the study. Level of statistical significance was set at P<0.05. The approval of the ethical committee of the Universite des Montagnes was also obtained. RESULTS: During the period of our study, out of the 14,200 patients aged 2 months and 5 years who were hospitalized 522 premature deaths were registered. This gives an incidence of 4.9%, representing 74.3% of all hospitalized deaths in this age group. Considering the fact that some of the files had very little information, only 373 files were studied. The sex ratio was 1.2. More astonishing was that a majority of the deaths occurred between midnight and 8 am. The most frequent registered cases were patients with severe malaria (42.6%), severe sepsis (20.6%), and acute lower respiratory tract infections (RTI) (16.1%) cases. One third of the patients had a poor nutritional status. CONCLUSIONS: The reinforcement of preventive measures and programs targeting the health of children such as the Integrated Management of Childhood Diseases (IMCD) would be a major priority in proffering a solution to this phenomenon. PMID- 26835404 TI - Recurrent wheezing in children. AB - Recurrent wheezing have a significant morbidity and it's estimated that about one third of school-age children manifest the symptom during the first 5 years of life. Proper identification of children at risk of developing asthma at school age may predict long-term outcomes and improve treatment and preventive approach, but the possibility to identify these children at preschool age remains limited. For many years authors focused their studies to identify early children with recurrent wheezing at risk to develop asthma at school age. Different phenotypes have been proposed for a more precise characterization and a personalized plan of treatment. The main criticism concerns the inability to define stable phenotypes with the risk of overestimating or underestimating the characteristics of symptoms in these children. The aim of this review is to report the recent developments on the diagnosis and treatment of recurrent paediatric wheezing. PMID- 26835405 TI - Paediatric Fabry disease. AB - Fabry disease is a rare, progressive X-linked inborn error of the glycosphingolipid metabolic pathway. Mutations of the GLA gene result in deficiency of the lysosomal enzyme, alpha-galactosidase A (alpha-Gal A) with accumulation of glycosphingolipids, particularly globotriaosylceramide (GL3) in the vascular endothelium of various tissues. Accumulation of GL3 eventually leads to life threatening renal, cardiac and cerebrovascular complications typically in the third to fifth decades of life. The first signs and symptoms of classic Fabry disease however appear in childhood but diagnosis is often delayed. The symptoms most commonly experienced in childhood include neuropathic pain, gastrointestinal dysfunction, hyperhidrosis and heat intolerance. Timely diagnosis is important as early treatment with enzyme replacement therapy reduces GL3 accumulation, can stabilize disease progression and potentially prevent irreversible organ damage. Physicians should be familiar with the signs and symptoms of Fabry disease in childhood and be particularly vigilant for unusual or non-specific but recurrent or episodic symptoms. PMID- 26835406 TI - How to make the timely diagnosis to stabilize disease progression and prevent the organ damage from Fabry disease? PMID- 26835407 TI - Prof. David Sillence: genetics is not the same as unknown diseases. PMID- 26835408 TI - Attitude of Saudi Arabian adults towards consanguineous marriage. AB - BACKGROUND: Research on the attitudes of Saudi adults towards consanguinity is scarce. The study aimed to explore the attitudes towards consanguinity and its associations with socio-demographic characteristics in a sample of Saudi adults. METHODS: A cross-sectional study was conducted using a self-administered questionnaire. A total of 386 outpatient waiting-area attendees at King Abdul Aziz Medical City-Riyadh were included. Participants were asked about their socio demographic characteristics, attitude towards consanguinity and the reasons behind this. RESULTS: The positive attitude towards consanguinity among the study respondents was 48.1% with 95% confidence interval (42.91-53.33%). Social and traditional culture (59.9%) were found to be the predominant reasons for favoring consanguinity in Saudi Arabia. Evidence against a positive attitude towards consanguinity was noted in respondents who received medical information about consanguinity versus those who had not received medical information (42.3% vs. 57%, p-value = 0.008). According to the multivariate logistic model, the odds of a positive attitude towards consanguinity were 2 times higher for males (adjusted odds ratio [aOR]: 2.2; 95% CI: 1.147, 4.290) and 4.1 times higher in respondents in consanguineous marriages (aOR: 4.1; 95% CI: 2.350, 7.156). The odds of a positive attitude towards consanguinity were 50% less in respondents who received health information on consanguinity compared to those who had not received health information about consanguinity (aOR: 0.50; 95% CI: 0.253, 0.863). CONCLUSION: One in every two Saudi adults favors consanguinity however, Saudi men and women differ in their attitudes towards consanguinity. Receiving health information on consanguinity was associated with a negative attitude towards this practice. PMID- 26835409 TI - An assessment of patients' knowledge of osteoporosis in Qatar: A pilot study. AB - Osteoporosis is a disease that affects the bones. It leads to increased risk of fractures as a result of decreased bone mineral density. The goal of this study was to assess the general perception of osteoporosis as well as knowledge of lifestyle, risk factors, and preventive measures among patients in Qatar. The study was conducted between September 2013 and September 2014. The study subjects (n = 93) were patients diagnosed with osteoporosis who attended the Outpatient Rheumatology Clinic at Hamad General Hospital in Doha, Qatar. The results showed that those with a university or graduate degree had a significantly higher level of knowledge about osteoporosis (p = 0.009) than those with less education. Among those in our study, knowledge related to osteoporosis was principally obtained through media sources such as television and radio (39%). In conclusion, osteoporosis patients in Qatar need a better understanding of the disease. Identifying thought patterns related to the perception of osteoporosis and treatment might assist in building a foundation for management modalities and effective preventive strategies for the disease in Qatar. PMID- 26835410 TI - Headache in a high school student - a reminder of fundamental principles of clinical medicine and common pitfalls of cognition. AB - Primary headache disorders account for the majority of the cases of headache. Nevertheless, the primary objective of a physician, when encountered with a patient with headache is to rule out a secondary cause the headache. This entails a search for specific associated red-flag symptoms or signs that may indicate a serious condition, as well as a heightened suspicion of and evaluation for a don't miss diagnosis. We present a case of a high-school student whose first manifestation of systemic lupus erythematosus (SLE) was a headache due to cerebral venous and sinus thrombosis, initially misdiagnosed as tension-headache and 'ophthalmoplegic migraine' (now known as 'recurrent painful ophthalmoplegic neuropathy'). The patient made a complete neurological and radiological recovery after systemic anticoagulation and treatment of SLE. An analysis of the clinical errors and cognitive biases leading to delayed referral to hospital is presented. We highlight the fact that adherence to the fundamental principles of clinical medicine and enhancement of cognitive awareness is required to reduce diagnostic errors. PMID- 26835411 TI - Association of erythrocytes antioxidant enzymes and their cofactors with markers of oxidative stress in patients with sickle cell anemia. AB - BACKGROUND: Sickle cell anemia (SCA) is an inherited blood disease with known complications as a result of certain pathophysiological dysfunctions. It has been suggested that an increase in oxidative stress contributes to the incidence of these changes. OBJECTIVES: This study investigated the oxidant/antioxidant status of patients with SCA, and evaluated the effect of SCA on antioxidant enzymes and their cofactors. METHODS: The study included 42 patients with SCA (in steady state), and a control group of 50 age-matched individuals without SCA. Serum malondialdehyde (MDA), copper, zinc, ferritin and iron levels, red blood cell (RBC) superoxide dismutase (SOD) and catalase levels were measured for the SCA and control groups. RESULTS: Significantly lower levels of antioxidant enzymes (RBC SOD and catalase) and higher serum MDA levels (biomarker of oxidative stress) were found in SCA patients compared to the control group (all p < 0.001). Increased levels of serum ferritin, iron and copper and decreased zinc concentrations were also found in the SCA patients compared to the control group (all p < 0.001). In the SCA group, there were significant negative correlations between MDA levels and RBC SOD, RBC catalase, and serum zinc levels (p < 0.01), while a significant positive correlation between MDA with serum copper and iron levels (p < 0.01) was observed. CONCLUSION: SCA is associated with alterations in markers of oxidative stress including an increased MDA level, decreased antioxidant enzyme levels, and altered levels of enzyme cofactors (zinc, copper, and iron). This suggests that these antioxidant enzymes could be used as effective therapeutic targets for the treatment of this disease and supplementation of patients with substances with antioxidant properties may reduce the complications of this disease. PMID- 26835412 TI - Cortex-sparing infarction in triple cervical artery dissection following chiropractic neck manipulation. AB - BACKGROUND: Multivessel cervical dissection with cortical sparing is exceptional in clinical practice. CASE PRESENTATION: A 55-year-old man presented with acute onset neck pain with associated sudden onset right-sided hemiparesis and dysphasia after chiropractic manipulation for chronic neck pain. RESULTS AND DISCUSSION: Magnetic resonance imaging revealed bilateral internal carotid artery dissection and left extracranial vertebral artery dissection with bilateral anterior cerebral artery territory infarctions and large cortical-sparing left middle cerebral artery infarction. This suggests the presence of functionally patent and interconnecting leptomeningeal anastomoses between cerebral arteries, which may provide sufficient blood flow to salvage penumbral regions when a supplying artery is occluded. CONCLUSION: Chiropractic cervical manipulation can result in catastrophic vascular lesions preventable if these practices are limited to highly specialized personnel under very specific situations. PMID- 26835413 TI - Behavior Correlates of Post-Stroke Disability Using Data Mining and Infographics. AB - PURPOSE: Disability is a potential risk for stroke survivors. This study aims to identify disability risk factors associated with stroke and their relative importance and relationships from a national behavioral risk factor dataset. METHODS: Data of post-stroke individuals in the U.S (n=19,603) including 397 variables were extracted from a publically available national dataset and analyzed. Data mining algorithms including C4.5 and linear regression with M5s methods were applied to build association models for post-stroke disability using Weka software. The relative importance and relationship of 70 variables associated with disability were presented in infographics for clinicians to understand easily. RESULTS: Fifty-five percent of post-stroke patients experience disability. Exercise, employment and satisfaction of life were relatively important factors associated with disability among stroke patients. Modifiable behavior factors strongly associated with disability include exercise (OR: 0.46, P<0.01) and good rest (OR 0.37, P<0.01). CONCLUSIONS: Data mining is promising to discover factors associated with post-stroke disability from a large population dataset. The findings can be potentially valuable for establishing the priorities for clinicians and researchers and for stroke patient education. The methods may generalize to other health conditions. PMID- 26835414 TI - Applications of High-Throughput Clonogenic Survival Assays in High-LET Particle Microbeams. AB - Charged particle therapy is increasingly becoming a valuable tool in cancer treatment, mainly due to the favorable interaction of particle radiation with matter. Its application is still limited due, in part, to lack of data regarding the radiosensitivity of certain cell lines to this radiation type, especially to high-linear energy transfer (LET) particles. From the earliest days of radiation biology, the clonogenic survival assay has been used to provide radiation response data. This method produces reliable data but it is not optimized for high-throughput microbeam studies with high-LET radiation where high levels of cell killing lead to a very low probability of maintaining cells' clonogenic potential. A new method, therefore, is proposed in this paper, which could potentially allow these experiments to be conducted in a high-throughput fashion. Cells are seeded in special polypropylene dishes and bright-field illumination provides cell visualization. Digital images are obtained and cell detection is applied based on corner detection, generating individual cell targets as x-y points. These points in the dish are then irradiated individually by a micron field size high-LET microbeam. Post-irradiation, time-lapse imaging follows cells' response. All irradiated cells are tracked by linking trajectories in all time-frames, based on finding their nearest position. Cell divisions are detected based on cell appearance and individual cell temporary corner density. The number of divisions anticipated is low due to the high probability of cell killing from high-LET irradiation. Survival curves are produced based on cell's capacity to divide at least four to five times. The process is repeated for a range of doses of radiation. Validation shows the efficiency of the proposed cell detection and tracking method in finding cell divisions. PMID- 26835415 TI - The rs11515 Polymorphism Is More Frequent and Associated With Aggressive Breast Tumors with Increased ANRIL and Decreased p16 (INK4a) Expression. AB - Chromosome position 9p21 encodes three-tumor suppressors p16(INK4a), p14(ARF), and p15(INK4b) and the long non-coding RNA ANRIL (antisense non-coding RNA in the INK4 locus). The rs11515 single-nucleotide polymorphism in the p16 (INK4a) /p14 (ARF) 3'-untranslated region is associated with glioblastoma, melanoma, and other cancers. This study investigated the frequency and effect of rs11515 genotypes in breast cancer. Genomic DNA samples from 400 women (200 with and 200 without a diagnosis of breast cancer) were genotyped for the rs11515 major (C) and minor (G) alleles. The rs11515 polymorphism was also investigated in 108 heart tissues to test for tissue-specific effects. Four 9p21 transcripts, p16 (INK4a) , p14 (ARF) , p15 (INK4b) , and ANRIL were measured in breast tumors and myocardium using quantitative PCR. Heterozygotes (CG genotype) were more frequent in women with breast cancer compared to the control population (P = 0.0039). In those with breast cancer, the CG genotype was associated with an older age (P = 0.016) and increased lymph node involvement (P = 0.007) compared to homozygotes for the major allele (CC genotype). In breast tumors, the CG genotype had higher ANRIL (P = 0.031) and lower p16 (INK4a) (P = 0.006) expression compared to the CC genotype. The CG genotype was not associated with altered 9p21 transcripts in heart tissue. In breast cancer, the rs11515 CG genotype is more frequent and associated with a more aggressive tumor that could be due to increased ANRIL and reduced p16 (INK4a) expression. The absence of association between rs11515 genotypes and 9p21 transcripts in heart tissue suggests this polymorphism has tissue- or disease-specific functions. PMID- 26835417 TI - The Relevance of Gynecologic Oncologists to Provide High-Quality of Care to Women with Gynecological Cancer. AB - Gynecologic oncologists have an essential role to treat women with gynecological cancer. It has been demonstrated that specialized physicians who work in multidisciplinary teams to treat women with gynecological cancers are able to obtain the best clinical and oncological outcomes. However, the access to gynecologic oncologists for women with suspected gynecological cancer is scarce. Therefore, this review analyzes the importance of specialized care of women with ovarian, cervical, and endometrial cancer. In addition, the role of gynecologic oncologists who offer fertility-sparing treatment as well as their role in assisting general gynecologists and obstetricians is also reviewed. PMID- 26835419 TI - Inclusion of "Toxicological Review Expiry Dates" in Art Material Labels May Further Reduce the Risk of Chronic Toxicity, Including That of Cancer. PMID- 26835416 TI - Ubiquitin-Mediated Degradation of Aurora Kinases. AB - The Aurora kinases are essential regulators of mitosis in eukaryotes. In somatic cell divisions of higher eukaryotes, the paralogs Aurora kinase A (AurA) and Aurora kinase B (AurB) play non-overlapping roles that depend on their distinct spatiotemporal activities. These mitotic roles of Aurora kinases depend on their interactions with different partners that direct them to different mitotic destinations and different substrates: AurB is a component of the chromosome passenger complex that orchestrates the tasks of chromosome segregation and cytokinesis, while AurA has many known binding partners and mitotic roles, including a well-characterized interaction with TPX2 that mediates its role in mitotic spindle assembly. Beyond the spatial control conferred by different binding partners, Aurora kinases are subject to temporal control of their activation and inactivation. Ubiquitin-mediated proteolysis is a critical route to irreversible inactivation of these kinases, which must occur for ordered transition from mitosis back to interphase. Both AurA and AurB undergo targeted proteolysis after anaphase onset as substrates of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase, even while they continue to regulate steps during mitotic exit. Temporal control of Aurora kinase destruction ensures that AurB remains active at the midbody during cytokinesis long after AurA activity has been largely eliminated from the cell. Differential destruction of Aurora kinases is achieved despite the fact that they are targeted at the same time and by the same ubiquitin ligase, making these substrates an interesting case study for investigating molecular determinants of ubiquitin-mediated proteolysis in higher eukaryotes. The prevalence of Aurora overexpression in cancers and their potential as therapeutic targets add importance to the task of understanding the molecular determinants of Aurora kinase stability. Here, we review what is known about ubiquitin-mediated targeting of these critical mitotic regulators and discuss the different factors that contribute to proteolytic control of Aurora kinase activity in the cell. PMID- 26835418 TI - MicroRNA Targeting to Modulate Tumor Microenvironment. AB - Communication between stromal cells and tumor cells initiates tumor growth, angiogenesis, invasion, and metastasis. Stromal cells include cancer-associated fibroblasts, tumor-associated macrophages, pericytes, endothelial cells, and infiltrating immune cells. MicroRNAs (miRNAs) in the tumor microenvironment have emerged as key players involved in the development of cancer and its progression. miRNAs are small endogenous non-protein-coding RNAs that negatively regulate the expression of multiple target genes at post-transcriptional level and thereby control many cellular processes. In this review, we provide a comprehensive overview of miRNAs dysregulated in different stromal cells and their impact on the regulation of intercellular crosstalk in the tumor microenvironment. We also discuss the therapeutic significance potential of miRNAs to modulate the tumor microenvironment. Since miRNA delivery is quite challenging and the biggest hurdle for clinical translation of miRNA therapeutics, we review various non viral miRNA delivery systems that can potentially be used for targeting miRNA to stromal cells within the tumor microenvironment. PMID- 26835420 TI - The Influence of C-Ions and X-rays on Human Umbilical Vein Endothelial Cells. AB - Damage to the endothelium of blood vessels, which may occur during radiotherapy, is discussed as a potential precursor to the development of cardiovascular disease. We thus chose human umbilical vein endothelial cells as a model system to examine the effect of low- and high-linear energy transfer (LET) radiation. Cells were exposed to 250 kV X-rays or carbon ions (C-ions) with the energies of either 9.8 MeV/u (LET = 170 keV/MUm) or 91 MeV/u (LET = 28 keV/MUm). Subculture of cells was performed regularly up to 46 days (~22 population doublings) post irradiation. Immediately after exposure, cells were seeded for the colony forming assay. Additionally, at regular intervals, mitochondrial membrane potential (MMP) (JC-1 staining) and cellular senescence (senescence-associated beta-galactosidase staining) were assessed. Cytogenetic damage was investigated by the micronucleus assay and the high-resolution multiplex fluorescence in situ hybridization (mFISH) technique. Analysis of radiation-induced damage shortly after exposure showed that C-ions are more effective than X-rays with respect to cell inactivation or the induction of cytogenetic damage (micronucleus assay) as observed in other cell systems. For 9.8 and 91 MeV/u C-ions, relative biological effectiveness values of 2.4 and 1.5 were obtained for cell inactivation. At the subsequent time points, the number of micronucleated cells decreased to the control level. Analysis of chromosomal damage by mFISH technique revealed aberrations frequently involving chromosome 13 irrespective of dose or radiation quality. Disruption of the MMP was seen only a few days after exposure to X-rays or C-ions. Cellular senescence was not altered by radiation at any time point investigated. Altogether, our data indicate that shortly after exposure C-ions were more effective in damaging endothelial cells than X-rays. However, late damage to endothelial cells was not found for the applied conditions and endpoints. PMID- 26835422 TI - Medical Applications at CERN and the ENLIGHT Network. AB - State-of-the-art techniques derived from particle accelerators, detectors, and physics computing are routinely used in clinical practice and medical research centers: from imaging technologies to dedicated accelerators for cancer therapy and nuclear medicine, simulations, and data analytics. Principles of particle physics themselves are the foundation of a cutting edge radiotherapy technique for cancer treatment: hadron therapy. This article is an overview of the involvement of CERN, the European Organization for Nuclear Research, in medical applications, with specific focus on hadron therapy. It also presents the history, achievements, and future scientific goals of the European Network for Light Ion Hadron Therapy, whose co-ordination office is at CERN. PMID- 26835421 TI - O-GlcNAcylation and the Metabolic Shift in High-Proliferating Cells: All the Evidence Suggests that Sugars Dictate the Flux of Lipid Biogenesis in Tumor Processes. AB - Cancer cells are characterized by their high capability to proliferate. This imposes an accelerated biosynthesis of membrane compounds to respond to the need for increasing the membrane surface of dividing cells and remodeling the structure of lipid microdomains. Recently, attention has been paid to the upregulation of O-GlcNAcylation processes observed in cancer cells. Although O GlcNAcylation of lipogenic transcriptional regulators is described in the literature (e.g., FXR, LXR, ChREBP), little is known about the regulation of the enzymes that drive lipogenesis: acetyl co-enzyme A carboxylase and fatty acid synthase (FAS). The expression and catalytic activity of both FAS and O-GlcNAc transferase (OGT) are high in cancer cells but the reciprocal regulation of the two enzymes remains unexplored. In this perspective, we collected data linking FAS and OGT and, in so doing, pave the way for the exploration of the intricate functions of these two actors that play a central role in tumor growth. PMID- 26835423 TI - miR-130b-3p Upregulation Contributes to the Development of Thyroid Adenomas Targeting CCDC6 Gene. AB - We have previously studied the function of microRNAs (miRNAs) in thyroid cells using the differentiated rat thyroid PC Cl 3 cells that need thyrotropin (TSH) for their growth. The miRNA expression profile examination allowed the detection of a set of miRNAs downregulated and upregulated by TSH. Here, we first demonstrated that upregulation of miR-130b-3p occurs through a protein kinase A cAMP-responsive element binding protein (CREB)-dependent mechanism. Then, we analyzed its expression in human thyroid follicular adenomas, where a constitutive CREB activation is frequently present. miR-130b-3p results in upregulation with a high fold-change in most thyroid follicular adenomas. Then, we identified CCDC6, coding for a protein that interacts with CREB1 leading to the transcriptional repression of CREB1 target genes, as a target of this miRNA. The targeting of CCDC6 by miR-130b-3p likely accounts for the mechanism by which its upregulation contributes to the development of thyroid adenomas increasing CREB1 activity. PMID- 26835424 TI - Methylprednisolone Pulse Treatment of Graves' Ophthalmopathy Is Not Associated with Secondary Adrenocortical Insufficiency. AB - OBJECTIVE: Graves' ophthalmopathy (GO) is an inflammatory disease in the orbital region. The first-line medical treatment is glucocorticoids. An important potential side effect of glucocorticoid treatment is suppression of the hypothalamic-pituitary-adrenal (HPA) axis with impairment of endogenous cortisol production, implicating symptoms of adrenocortical insufficiency, especially in the period after cessation of therapy with possible risks in cases of intercurrent illness. The aim of this study was to evaluate HPA axis function before and after methylprednisolone pulse treatment of GO. STUDY DESIGN: HPA axis function was evaluated by measurements of plasma ACTH and an ACTH stimulation test with plasma cortisol measurements at 0 and 30 min after an intravenous bolus of synthetic ACTH (Synacthen(r) 250 ug). This was done in 12 patients with GO before and at cessation of methylprednisolone pulse treatment (500 mg i.v. per week for 6 weeks followed by 250 mg i.v. per week for an additional 6 weeks). RESULTS: All patients included fulfilled the criteria of intact HPA axis function before and at cessation of methylprednisolone pulse treatment. Data are given as medians (with ranges). Before glucocorticoid treatment basal plasma cortisol was 290 nM (196-579) and 786 nM (612-1,050) after ACTH stimulation. At cessation of therapy the corresponding values were 309 nM (88-718) and 852 nM (524-1,011), respectively. Thus, all patients passed a 30-min stimulated plasma cortisol of 500 nM. Before treatment plasma ACTH was 4.2 pmol/l (4-16) and at cessation of therapy the corresponding value was 4.8 pmol/l (2-9; p = 0.27). CONCLUSION: Transient suppression of the HPA axis with secondary adrenocortical insufficiency does not seem to be a common phenomenon after intravenous methylprednisolone pulse therapy for GO. Therefore, routine precautions are not necessary. However, our results do not exclude that transient secondary adrenocortical insufficiency might occur occasionally. PMID- 26835426 TI - Nonrecurrent Laryngeal Nerve and Associated Anatomical Variations: The Art of Prediction. AB - INTRODUCTION: A nonrecurrent laryngeal nerve (NRLN) is a rare anatomical variation in which the nerve enters the larynx directly off the cervical vagus nerve. CASE REPORT: We present 2 patients who underwent thyroid surgery for benign disease. Intraoperatively, type 2a and 1 NRLN were identified. Due to the frequent association with a vascular abnormality, an ultrasound and a computed tomography were performed which showed a right aberrant subclavian artery with a retroesophageal course and a common trunk of the common carotids in both patients. DISCUSSION AND CONCLUSION: The presence of an NRLN is a major risk during surgical procedures and the surgeon should be aware of the possibility of its existence. NRLN may be associated with rare vascular anomalies, such as arteria lusoria and a bicarotid trunk. This paper reveals this association in 2 patients for the first time. PMID- 26835425 TI - IFNgamma-Inducible Chemokines Decrease upon Selenomethionine Supplementation in Women with Euthyroid Autoimmune Thyroiditis: Comparison between Two Doses of Selenomethionine (80 or 160 MUg) versus Placebo. AB - BACKGROUND: Several studies have suggested that selenium may influence the natural history of autoimmune thyroiditis (AIT). Recently, IFNgamma-inducible chemokines (CXCL-9, -10 and -11) were shown to be elevated in AIT patients. OBJECTIVE: This prospective, randomized, controlled study was conducted to evaluate the effect of two doses of selenomethionine (Semet; 80 or 160 ug/day) versus placebo in euthyroid women with AIT, in terms of reduction of anti-thyroid antibodies, CXCL-9, -10 and -11 and improvement of thyroid echogenicity, over 12 months. PATIENTS AND METHODS: Sixty patients, aged 21-65 years, were equally randomized into 3 groups: placebo, 80 ug/day of Semet (80-Semet) or 160 ug/day of Semet (160-Semet). RESULTS: Anti-thyroperoxidase antibody (TPOAb) levels remained unaffected by Semet supplementation; anti-thyroglobulin antibody levels showed a significant reduction in the 160-Semet and the placebo group at 12 months. No significant change in thyroid echogenicity, thyroid volume and quality of life was observed within and between the groups. Subclinical hypothyroidism was diagnosed in 2 patients of the placebo group versus 1 patient in each Semet group. Serum CXCL-9 and -10 were significantly reduced in both Semet groups at 6 and 12 months, while they remained unchanged or increased in the placebo group. CXCL-11, TNFalpha and IFNgamma showed a transient decrease at 6 months in both Semet groups but returned nearly to the basal levels at 12 months. CONCLUSIONS: Semet supplementation had no positive effect on thyroid echogenicity or TPOAb in our patients. However, we observed a Semet-dependent downregulation of the IFNgamma-inducible chemokines, especially CXCL-9 and -10, which may serve as helpful biomarkers in future selenium supplementation trials. PMID- 26835427 TI - Clinical Utility of SPECT/CT Imaging Post-Radioiodine Therapy: Does It Enhance Patient Management in Thyroid Cancer? AB - BACKGROUND: The aim of this study was to evaluate post-therapy iodine-131 single photon emission computed tomography/computed tomography ((131)I-SPECT/CT) imaging in comparison to conventional planar (131)I whole-body imaging, and to assess its clinical impact on the management of patients. METHODS: We retrospectively reviewed planar (131)I whole-body and (131)I-SPECT/CT imaging findings in 67 patients who underwent (131)I therapy for thyroid cancer. Two nuclear medicine physicians reviewed the scans independently. The foci of increased tracer uptake were identified in the neck, thorax and elsewhere. Within the neck, the foci of (131)I-increased uptake were graded qualitatively as probable or definite uptake in thyroid remnants and probable or definite uptake in the lymph nodes. Serum thyroglobulin level, histopathology and other imaging findings served as the reference standard. RESULTS: Of the 67 patients, 57 (85%) had radioiodine avid disease and 10 (15%) demonstrated non-radioiodine avid disease. Overall, post therapy (131)I-SPECT/CT downstaged lymph node staging in 10 patients and upstaged it in 4 patients. This translated into a change of management for 9/57 (16%) patients with radioiodine avid disease. A change of management was observed in 5/10 patients with non-radioiodine avid disease confirmed in the post-(131)I SPECT/CT study. Additionally, clinically significant findings such as incidental lung cancer, symptomatic pleural effusion and consolidation were also diagnosed in both groups of patients. CONCLUSION: In patients with thyroid cancer, (131)I SPECT/CT is a valuable addition to standard post-therapy planar imaging. SPECT/CT also improved diagnostic confidence and provided crucial clinical information leading to change of management for a significant number of these patients. PMID- 26835428 TI - Outcome of Subclassification of Indeterminate (Thy-3) Thyroid Cytology into Thy 3a and Thy-3f. AB - OBJECTIVES: The British Thy system is a widely used classification system for reporting thyroid fine-needle aspiration (FNA) cytology. The Royal College of Pathologists in 2009 recommended the subdivision of the Thy-3 (indeterminate) category into Thy-3a (atypia) and Thy-3f (follicular neoplasm). Our objective was to examine the malignancy rates of Thy-3a and Thy-3f cases at our institution and to investigate whether the risk of malignancy in Thy-3a cases is reduced by FNA on a different occasion showing benign cytology. METHODS: This is a retrospective study of 748 thyroid nodules undergoing 1,032 FNAs, with indeterminate (Thy-3) cytology subdivided into Thy-3a and Thy-3f. Cases were correlated with final histology in surgical cases. Incidental carcinomas occurring outside the biopsied nodule were discounted. RESULTS: A total of 109 nodules had a final cytological diagnosis of Thy-3a, of which 67 underwent surgery, with an incidence of malignancy of 13.4% (9/67); 90 nodules had a final cytological diagnosis of Thy 3f, of which 84 underwent surgery, with an incidence of malignancy of 17.9% (15/84). The difference in malignancy rates was not significant (p = 0.51). The incidence of malignancy in nodules with benign and Thy-3a cytology on separate occasions was not significantly different from cases with a single Thy-3a cytology. CONCLUSIONS: Thyroid nodules with Thy-3a cytology have a slightly lower risk of malignancy than Thy-3f cases. However, the difference is not significant and does not appear to be reduced by FNA on a separate occasion showing benign cytology. Management decisions for patients with Thy-3a cytology should be taken carefully to avoid missing cancers. PMID- 26835429 TI - Trends in Thyroid Cancer Incidence in Korean Children (1999-2012) Based on Palpation and Nonpalpation Detection Methods. AB - BACKGROUND: The incidence of childhood thyroid cancer is increasing in several populations; however, contributing factors have not been adequately discussed. OBJECTIVES: Our aim was to identify trends of childhood thyroid cancer based on the Korea Central Cancer Registry (KCCR) database and to elucidate changes in detection methods of cancers using a single-center database. METHODS: Data from the KCCR and Statistics Korea between 1999 and 2012 were used to calculate the crude incidence of thyroid cancer in children. To analyze detection methods for cancers, pediatric patients (aged 0-19 years, n = 126) who underwent thyroid surgery for thyroid cancers at our institution were identified. Subjects were divided into two groups by detection method: (1) palpation group and (2) screening group. RESULTS: The crude incidence of childhood thyroid cancer increased from 0.5 per 100,000 in 1999 to 1.7 in 2012. The proportion of thyroid cancer among total cancers also increased from 4.4% in 1999 to 10.6% in 2012. Among 126 children from our institution, 91 cases (72%) were identified as palpable neck masses, and the remainder were discovered during imaging studies. The numbers in both groups gradually increased during the study period. CONCLUSIONS: The incidence of childhood thyroid cancer has steadily increased in Korea. Regarding the detection methods of cancers, most tumors are detected by palpation rather than screening, although the rate of masses identified during screening has increased. PMID- 26835430 TI - Follicular Thyroid Carcinoma: Disease Response Evaluation Using American Thyroid Association Risk Assessment Guidelines. AB - OBJECTIVE: To evaluate the overall and progression-free survival for follicular thyroid carcinoma (FTC) based on the American Thyroid Association (ATA) staging system for recurrence risk assessment and the TNM staging system. METHODS: A clinical review of FTC patients between 1995 and 2014 was conducted at a single center. The data was classified using the TNM staging system into low, intermediate, and high risk of recurrence as per the ATA risk assessment. RESULTS: Over the course of 19 years, 114 (11.9%) of all of the thyroid cancer patients presenting to our hospital had FTC (i.e. 78 females and 36 males). The age range was 15-80 years. Ninety-four tumors were resectable and 18 were unresectable. Sixteen patients were excluded due to insufficient information on their recurrence risk. Based on the ATA categorization, 36 patients had a low recurrence risk. All patients were alive at the time of categorization, and 1 showed progressive disease. Thirty-eight patients had an intermediate recurrence risk. One patient died and 2 showed progression. Twenty-four had a high recurrence risk. Seven patients died and 6 showed progression. In terms of TNM stages, 2 (3.2%) stage I, 3 (17.6%) stage II, 1 (14%) stage III, and 2 (12.5%) stage IV patients died during follow-up. Both ATA risk classification and TNM staging were significant predictors of disease-free survival. On bivariate analysis, the ATA classification (HR 4.67; 95% CI 1.74-12.5, p = 0.002) was a better predictor of survival compared to the TNM classification (HR 1.26; 95% CI 0.98-1.62, p = 0.063). CONCLUSION: ATA risk stratification predicts the disease recurrence rate and survival better than TNM staging. Age does not have an association; the risk category with dynamic reassessment effectively better predicts the course of disease in FTC. PMID- 26835431 TI - Hypertrophic Osteoarthropathy and Follicular Thyroid Cancer: A Rare Paraneoplastic Syndrome. AB - BACKGROUND: Hypertrophic osteoarthropathy (HOA) is a rare condition characterized by bone and joint pain and digital clubbing usually associated with bronchopulmonary diseases. Primary HOA is rare and the pathogenesis remains unclear. OBJECTIVES: Cases of HOA as a paraneoplastic syndrome associated with thyroid carcinoma are very rare - only 2 cases have been described in the literature. RESULTS: We present the first case of a 40-year-old patient affected by HOA associated with invasive differentiated follicular thyroid carcinoma operated in 2 stages. Both operations were followed by radioiodine ablation, and then a rapid unresectable local recurrence developed requiring cervical radiotherapy (70 Gy). A second treatment with 100 mCi of (131)I confirmed it was a refractory thyroid cancer. Further surgery confirmed a poorly differentiated follicular cancer and 12 cycles of chemotherapy by gemcitabine and oxaliplatin followed. During the 8 years of follow-up, cervical recurrence was stable, but severe episodes of hemoptysis occurred requiring iterative embolization of the bronchial and tracheal arteries. Other lung diseases were excluded. Digital clubbing appeared, which was associated with arthritis, bone pain and inflammatory syndrome. X-rays and magnetic resonance imaging found periosteal apposition in the long bones; bone scintigraphy confirmed the HOA diagnosis. Other causes of arthritis were eliminated. She was treated with colchicine, corticosteroids and nonsteroidal anti-inflammatory drugs, but only the combination of methotrexate and hydroxychloroquine reduced the morphine requirements. CONCLUSION: HOA is exceptionally associated with thyroid cancer and we raised the hypothesis of the secretion of a circulating factor in a patient with invasive and recurrent follicular thyroid cancer, refractory to radioiodine. PMID- 26835432 TI - Standardization of Free T4 and Harmonization of TSH Measurements: A Request for Input from Endocrinologists and Other Physicians. PMID- 26835433 TI - Is Confirmed Elevation of the Serum TSH with Normal Concentrations of Circulating Thyroid Hormones Sufficient for the Diagnosis of Subclinical Hypothyroidism? PMID- 26835436 TI - Surgical Stabilization of Femur Fractures in Post-Traumatic Hypoxemic Patients: When and Why? AB - BACKGROUND: Post-traumatic hypoxemia can deteriorate during operative manipulations. OBJECTIVES: In the present study, criteria-based approach was applied to determine optimum conditions for femur surgery. The aim of this study was to optimize perioperative management of post-traumatic hypoxemia. PATIENTS AND METHODS: In this prospective observational study, post-traumatic adults with PaO2 < 70 mmHg in room air were enrolled. Physiological parameters, O2 saturation (SO2), arterial blood gas (ABG) analysis, Schonfeld fat embolism index score (SS), and Murray's lung injury scores (LIS) were assessed. The management protocol was femur surgery when patient was hemodynamically stable with LIS < 2.5 and PaO2/FiO2 > 200 mmHg (FiO2 < 0.5, PEEP < 8 cm H2O). RESULTS: A total of 31 adults (26 males and 5 females) with LIS of 0.1 to 2.5 (26 patients) and > 2.5 (five patients) at admission were recruited. Sixteen patients were admitted within 24 hours and 15 between 24 and 90 hours after injury. Thirteen patients were operated within 24 hours. Post-operative LIS was improved. No adverse sequels or mortality were seen. CONCLUSIONS: Appropriate surgical stabilization can be safely performed during established post-traumatic hypoxemia using a multidisciplinary approach, continuous monitoring, and serial investigations to diagnose fulminant pathology and associated injuries. PMID- 26835435 TI - Salmonella enterica Serovar Typhimurium Exploits Inflammation to Modify Swine Intestinal Microbiota. AB - Salmonella enterica serovar Typhimurium is an important zoonotic gastrointestinal pathogen responsible for foodborne disease worldwide. It is a successful enteric pathogen because it has developed virulence strategies allowing it to survive in a highly inflamed intestinal environment exploiting inflammation to overcome colonization resistance provided by intestinal microbiota. In this study, we used piglets featuring an intact microbiota, which naturally develop gastroenteritis, as model for salmonellosis. We compared the effects on the intestinal microbiota induced by a wild type and an attenuated S. Typhimurium in order to evaluate whether the modifications are correlated with the virulence of the strain. This study showed that Salmonella alters microbiota in a virulence-dependent manner. We found that the wild type S. Typhimurium induced inflammation and a reduction of specific protecting microbiota species (SCFA-producing bacteria) normally involved in providing a barrier against pathogens. Both these effects could contribute to impair colonization resistance, increasing the host susceptibility to wild type S. Typhimurium colonization. In contrast, the attenuated S. Typhimurium, which is characterized by a reduced ability to colonize the intestine, and by a very mild inflammatory response, was unable to successfully sustain competition with the microbiota. PMID- 26835438 TI - Who Is Responsible for Work-Life Balance? PMID- 26835434 TI - Vaccination with DNA Encoding Truncated Enterohemorrhagic Escherichia coli (EHEC) Factor for Adherence-1 Gene (efa-1') Confers Protective Immunity to Mice Infected with E. coli O157:H7. AB - Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is the predominant causative agent of hemorrhagic colitis in humans and is the cause of haemolytic uraemic syndrome and other illnesses. Cattle have been implicated as the main reservoir of this organism. Here, we evaluated the immunogenicity and protective efficacy of a DNA vaccine encoding conserved sequences of truncated EHEC factor for adherence-1 (efa-1') in a mouse model. Intranasal administration of plasmid DNA carrying the efa-1' gene (pVAXefa-1') into C57BL/6 mice elicited both humoral and cellular immune responses. In animals immunized with pVAXefa-1', EHEC-secreted protein-specific IgM and IgG antibodies were detected in sera at day 45. Anti EHEC-secreted protein sIgA was also detected in nasal and bronchoalveolar lavages. In addition, antigen-specific T-cell-proliferation, IL-10, and IFN-gamma were observed upon re-stimulation with either heat-killed bacteria or EHEC secreted proteins. Vaccinated animals were also protected against challenge with E. coli O157:H7 strain EDL933. These results suggest that DNA vaccine encoding efa-1' have therapeutic potential in interventions against EHEC infections. This approach could lead to a new strategy in the production of vaccines that prevent infections in cattle. PMID- 26835437 TI - Small-area variation in screening for cancer, glucose and cholesterol in Ontario: a cross-sectional study. AB - BACKGROUND: Screening for cervical, breast and colon cancers, and elevations of cholesterol and glucose, reduces premature cause-specific mortality from these cancers and circulatory diseases. Despite primary care reforms and incentives, and promotion of cancer-screening programs among individuals, participation is suboptimal. We aimed to examine participation as of Dec. 31, 2011, by factors of deprivation, demographics and primary care at the small-area level. METHODS: From health care administrative databases, we identified people eligible for each screening test, and their participation, in each dissemination area (referred to as small areas, n = 18 950) in Ontario. We calculated rates for each test among small areas (overall and stratified by demographic, socioeconomic and primary care descriptors) and stratified by sex for all tests combined. We loaded all data into a geographic information system. Funnel plots were generated showing the percentage of eligible people who completed screening for all tests by small area, stratified by sex. Overall and stratified screening prevalence ratios were calculated among small areas. RESULTS: Among small areas, the mean and SD for participation in all tests combined was 31.6% (SD 11.0%) for women and 41.2% (SD 12.0%) for men. Screening prevalence among small areas, for each test and for all tests combined, overall and stratified by sex, declined with decreasing percentage with high school completion, decreasing socioeconomic quintile, and decreasing percentage with an identifiable primary care physician. INTERPRETATION: Our results show that the rate of participation in all eligible screening tests among small areas is much lower than the rate of participation in any one particular test. This finding has implications for the design and implementation of strategies to improve rates of screening. PMID- 26835439 TI - We Can, but Should We? PMID- 26835440 TI - Concordance of Expert and Parental Opinion about Hypospadias Surgical Outcome Is Severity Dependent. AB - INTRODUCTION: Hypospadias is a male congenital condition where the opening of the urethral meatus is not located in the typical anatomical position. It has been a challenge for empirical studies to ascertain the level of concordance of opinion among parents and urologists with regard to surgical outcomes according to hypospadias severity. MATERIALS AND METHODS: Parents of children who had undergone hypospadias repair were recruited for this study (n = 104). A set of questionnaires that included some items with Likert scale were created to evaluate postsurgical satisfaction by parents and urologists. SAHLSA-50, a validated instrument for adult Spanish-speaking adults, was used to assess health literacy. Cohen's kappa (kappa) coefficient was used to assess interobserver agreement and Chi Square "Goodness of Fit" Test was used to determine probability of satisfaction. FINDINGS: Concordance on the level of satisfaction with surgical outcomes for Type cases I was slight (kappa = 0.20; CI 95% 0-0.60), for Type II cases was moderate (kappa = 0.54; CI 95% 0.13-0.94), and for Type III cases was substantial (kappa = 0.62; CI 95% 0-0.56). However, the probability of satisfaction did not change according to severity (Chi Square "Goodness of Fit" Test; parents, p = 0.84; pediatric urologists, p = 0.92). These results cannot be explained by parental health literacy according to SAHLSA-50 test scores. CONCLUSION: The level of concordance of opinion among parents and urologists with regard to their level of satisfaction with surgical outcomes is related to hypospadias severity, whereby the greatest level of concordance of opinion was achieved among most severe cases. This study underscores the need for longer follow-up to properly assess satisfaction with hypospadias repair, especially for the less severe forms of the condition. PMID- 26835441 TI - Global Health Policy and Access to Care: Investigating Patient Choice on an International Level Using Social Media. AB - BACKGROUND: Increased access to transportation and information has led to the emergence of more diverse patient choice and new forms of health care consumption, such as medical travel. In order for health care providers to effectively attract patients, more knowledge is needed on the mechanisms underlying decision-making of potential travelers from different countries. A particularly promising method of studying the travelers' motives is collecting data on social media. OBJECTIVES: The aim of this study was to test what factors influence decision-making of potential medical travelers and how these factors interact. Based on existing literature, the factors analyzed included quality, cost, and waiting time for 2 procedures varying in invasiveness across 12 different destination countries. METHODS: Decision-making patterns were examined using a pilot questionnaire that generated a large amount of data from over 800 participants in 40 countries. Participants indicated their willingness to travel given different scenarios. Each scenario consisted of a combination of several factors. Additionally, participants were asked to indicate the reasons for their choice. RESULTS: Individuals display high willingness to travel for medical care when combining all participants and scenarios, travel for care was chosen 66.9% of the time. Among the factors influencing their decisions, quality of the medical procedure abroad was considered most important, and cost was least important as shown by chi-square tests and corresponding odds ratios. Log-linear analyses revealed an interaction between time waiting in the local health care system and type of procedure, whereby time pressure increased the odds of agreeing to travel for the more invasive procedure. The odds of traveling to Europe and the USA were by far the highest, although participants indicated that under certain conditions they might be willing to travel to other medical destinations, such as Asia. CONCLUSION: Our measurements yielded several reliable insights into the factors driving medical decision-making. An essential next step would be to expand these findings with a more encompassing sample and more elaborate statistical modeling. PMID- 26835442 TI - Responses of Aboriginal and Torres Strait Islander Primary Health-Care Services to Continuous Quality Improvement Initiatives. AB - BACKGROUND: Indigenous primary health-care (PHC) services participating in continuous quality improvement (CQI) cycles show varying patterns of performance over time. Understanding this variation is essential to scaling up and sustaining quality improvement initiatives. The aim of this study is to examine trends in quality of care for services participating in the ABCD National Research Partnership and describe patterns of change over time and examine health service characteristics associated with positive and negative trends in quality of care. SETTING AND PARTICIPANTS: PHC services providing care for Indigenous people in urban, rural, and remote northern Australia that had completed at least three annual audits of service delivery for at least one aspect of care (n = 73). METHODS/DESIGN: Longitudinal clinical audit data from use of four clinical audit tools (maternal health, child health, preventive health, Type 2 diabetes) between 2005 and 2013 were analyzed. Health center performance was classified into six patterns of change over time: consistent high improvement (positive), sustained high performance (positive), decline (negative), marked variability (negative), consistent low performance (negative), and no specific increase or decrease (neutral). Backwards stepwise multiple logistic regression analyses were used to examine the associations between health service characteristics and positive or negative trends in quality of care. RESULTS: Trends in quality of care varied widely between health services across the four audit tools. Regression analyses of health service characteristics revealed no consistent statistically significant associations of population size, remoteness, governance model, or accreditation status with positive or negative trends in quality of care. CONCLUSION: The variable trends in quality of care as reflected by CQI audit tools do not appear to be related to easily measurable health service characteristics. This points to the need for a deeper or more nuanced understanding of factors that moderate the effect of CQI on health service performance for the purpose of strengthening enablers and overcoming barriers to improvement. PMID- 26835443 TI - Perceived Usefulness of a Microfinance Intervention on Health Awareness and Practices in Nepal. AB - BACKGROUND: Economic constraints may lead to poor health among people from the developing world. Microfinance has proven to be useful in improving health outcomes elsewhere, but it still remains a neglected issue in Nepal. This study aims to assess perceived usefulness of the microfinance on health awareness and practices among different ethnic groups of Nepal. METHOD: A community-based cross sectional study was conducted in four districts of western Nepal. A total of 500 microfinance clients representing different ethnic groups (upper caste, aadibasi and janajati, and dalit) were selected by using systemic random sampling. Health awareness and practices among different ethnic groups were compared by logistic regression after adjustment for age, level of education, sex of household heads, occupation, and place of residence. Since participants were asked about their health awareness and practices, before and after microfinance intervention, during a single interview, there was a strong possibility of recall bias with respect to their preintervention awareness and other measures. RESULTS: Microfinance intervention positively influenced self-reported health awareness and practices among different ethnic groups in Nepal, which was highest among the upper caste group (77-92%, rate ratios around 1.7-2.6), followed by the aadibasi/janajati (60-76%, rate ratios around 1.4-1.8) and dalit group (33-52%, reference group). Self-reported awareness about environment and sanitation, family planning methods, and available health services at local level improved from 11.2 to 69.2, 9.2 to 65.0, and 3.8 to 59.8%, respectively, among the clients after microfinance intervention (p < 0.001). Similarly, the practices of eating nutritious food/balanced diet, drinking safe water, using toilet, immunizing the children, and regularly visiting the healthcare facility were improved from 4.2 to 63.8, 12.6 to 66.8, 15.2 to 70.4, 15.8 to 73.8, and 3.6 to 61.4%, respectively (p < 0.001). CONCLUSION: Despite lack of control group and potential recall bias, this study reports positive effect of microfinance on self-reported health awareness and practices among different ethnic groups of Nepal. This finding supports further implementation and evaluation of equity-based microfinance to improve health and economic conditions of Nepalese people. PMID- 26835444 TI - Editorial: Health Care Financing and Affordability in the Emerging Global Markets. PMID- 26835445 TI - Optimal Versus Realized Trajectories of Physiological Dysregulation in Aging and Their Relation to Sex-Specific Mortality Risk. AB - While longitudinal changes in biomarker levels and their impact on health have been characterized for individual markers, little is known about how overall marker profiles may change during aging and affect mortality risk. We implemented the recently developed measure of physiological dysregulation based on the statistical distance of biomarker profiles in the framework of the stochastic process model of aging, using data on blood pressure, heart rate, cholesterol, glucose, hematocrit, body mass index, and mortality in the Framingham original cohort. This allowed us to evaluate how physiological dysregulation is related to different aging-related characteristics such as decline in stress resistance and adaptive capacity (which typically are not observed in the data and thus can be analyzed only indirectly), and, ultimately, to estimate how such dynamic relationships increase mortality risk with age. We found that physiological dysregulation increases with age; that increased dysregulation is associated with increased mortality, and increasingly so with age; and that, in most but not all cases, there is a decreasing ability to return quickly to baseline physiological state with age. We also revealed substantial sex differences in these processes, with women becoming dysregulated more quickly but with men showing a much greater sensitivity to dysregulation in terms of mortality risk. PMID- 26835448 TI - Under the Cartagena Protocol on Biosafety - Where is the Roadmap for Risk Assessment Taking Us? AB - The paper summarizes the history of the development of the guidance on risk assessment, including the roadmap under the Cartagena Protocol on Biosafety since 2008 until now. The aim and the contents of the roadmap for risk assessment of living modified organisms (LMOs) are described, in particular the five steps in the risk assessment process. After several rounds of discussions at the expert and political level, the guidance including the roadmap is currently revised taking into account the results of an in-depth practical testing process by the Parties, Non-Parties, and relevant organizations. The aim is to provide an improved version of the guidance for endorsement and broad support by the next meeting of the Parties to the Cartagena Protocol in December 2016. PMID- 26835449 TI - Voice Pathology Detection Using Modulation Spectrum-Optimized Metrics. AB - There exist many acoustic parameters employed for pathological assessment tasks, which have served as tools for clinicians to distinguish between normophonic and pathological voices. However, many of these parameters require an appropriate tuning in order to maximize its efficiency. In this work, a group of new and already proposed modulation spectrum (MS) metrics are optimized considering different time and frequency ranges pursuing the maximization of efficiency for the detection of pathological voices. The optimization of the metrics is performed simultaneously in two different voice databases in order to identify what tuning ranges produce a better generalization. The experiments were cross validated so as to ensure the validity of the results. A third database is used to test the optimized metrics. In spite of some differences, results indicate that the behavior of the metrics in the optimization process follows similar tendencies for the tuning databases, confirming the generalization capabilities of the proposed MS metrics. In addition, the tuning process reveals which bands of the modulation spectra have relevant information for each metric, which has a physical interpretation respecting the phonatory system. Efficiency values up to 90.6% are obtained in one tuning database, while in the other, the maximum efficiency reaches 71.1%. Obtained results also evidence a separability between normophonic and pathological states using the proposed metrics, which can be exploited for voice pathology detection or assessment. PMID- 26835450 TI - Editorial: Inorganic Biomaterials. PMID- 26835446 TI - Regulatory Crosstalk by Protein Kinases on CFTR Trafficking and Activity. AB - Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a member of the ATP binding cassette (ABC) transporter superfamily that functions as a cAMP-activated chloride ion channel in fluid-transporting epithelia. There is abundant evidence that CFTR activity (i.e., channel opening and closing) is regulated by protein kinases and phosphatases via phosphorylation and dephosphorylation. Here, we review recent evidence for the role of protein kinases in regulation of CFTR delivery to and retention in the plasma membrane. We review this information in a broader context of regulation of other transporters by protein kinases because the overall functional output of transporters involves the integrated control of both their number at the plasma membrane and their specific activity. While many details of the regulation of intracellular distribution of CFTR and other transporters remain to be elucidated, we hope that this review will motivate research providing new insights into how protein kinases control membrane transport to impact health and disease. PMID- 26835447 TI - Synthetic Peptides as Protein Mimics. AB - The design and generation of molecules capable of mimicking the binding and/or functional sites of proteins represents a promising strategy for the exploration and modulation of protein function through controlled interference with the underlying molecular interactions. Synthetic peptides have proven an excellent type of molecule for the mimicry of protein sites because such peptides can be generated as exact copies of protein fragments, as well as in diverse chemical modifications, which includes the incorporation of a large range of non proteinogenic amino acids as well as the modification of the peptide backbone. Apart from extending the chemical and structural diversity presented by peptides, such modifications also increase the proteolytic stability of the molecules, enhancing their utility for biological applications. This article reviews recent advances by this and other laboratories in the use of synthetic protein mimics to modulate protein function, as well as to provide building blocks for synthetic biology. PMID- 26835452 TI - Carnosine Content in Skeletal Muscle Is Dependent on Vitamin B6 Status in Rats. AB - Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is involved in amino acid metabolisms in the body as a cofactor. We hypothesized that enzymes involved in beta-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP dependent. Thus, we examined the effects of dietary vitamin B6 on the muscle carnosine content of rats. Male and female rats were fed a diet containing 1, 7, or 35 mg pyridoxine (PN) HCl/kg for 6 weeks. Carnosine in skeletal muscles was quantified by ultra-performance liquid chromatography coupled with tandem mass spectrometry. In the gastrocnemius muscle of male rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+70 and +61%, respectively) than in the 1 mg PN HCl/kg group, whereas that in the soleus muscle of male rats was significantly higher only in the 7 mg group (+43%) than in the 1 mg PN HCl/kg group (P < 0.05). In both muscles of female rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+32 to +226%) than in the 1 mg PN HCl/kg group (P < 0.05). We also found that, compared to the 1 mg group, beta alanine concentrations in the 7 and 35 mg groups were markedly elevated in gastrocnemius muscles of male (+153 and +148%, respectively, P < 0.05) and female (+381 and +437%, respectively, P < 0.05) rats. Noteworthy, the concentrations of ornithine in the 7 and 35 mg groups were decreased in gastrocnemius muscles of male rats (-46 and -54%, respectively, P < 0.05), which strongly inversely correlated with beta-alanine concentration (r = -0.84, P < 0.01). In humans, 19% lower muscle carnosine content was found in soleus muscle of women of the lower plasma PLP tertile, but this was not observed in gastrocnemius muscle or in men. We conclude that adequate dietary vitamin B6 is essential for maintaining carnosine in skeletal muscles of rats. Significantly lower soleus carnosine content among women close to PLP deficiency suggests that a similar phenomenon exists in the humans. PMID- 26835451 TI - Carbonate Precipitation through Microbial Activities in Natural Environment, and Their Potential in Biotechnology: A Review. AB - Calcium carbonate represents a large portion of carbon reservoir and is used commercially for a variety of applications. Microbial carbonate precipitation, a by-product of microbial activities, plays an important metal coprecipitation and cementation role in natural systems. This natural process occurring in various geological settings can be mimicked and used for a number of biotechnologies, such as metal remediation, carbon sequestration, enhanced oil recovery, and construction restoration. In this study, different metabolic activities leading to calcium carbonate precipitation, their native environment, and potential applications and challenges are reviewed. PMID- 26835454 TI - Commentary: Are the proposed benefits of melatonin-rich foods too hard to swallow? PMID- 26835453 TI - Severe but Not Moderate Vitamin B12 Deficiency Impairs Lipid Profile, Induces Adiposity, and Leads to Adverse Gestational Outcome in Female C57BL/6 Mice. AB - Vitamin B12 deficiency is widely prevalent in women of childbearing age, especially in developing countries. In the present study, through dietary restriction, we have established mouse models of severe and moderate vitamin B12 deficiencies to elucidate the impact on body composition, biochemical parameters, and reproductive performance. Female weanling C57BL/6 mice were fed for 4 weeks: (a) control AIN-76A diet, (b) vitamin B12-restricted AIN-76A diet with pectin as dietary fiber (severe deficiency group, as pectin inhibits vitamin B12 absorption), or (c) vitamin B12-restricted AIN-76A diet with cellulose as dietary fiber (moderate deficiency group as cellulose does not interfere with vitamin B12 absorption). After confirming deficiency, the mice were mated with male colony mice and maintained on their respective diets throughout pregnancy, lactation, and thereafter till 12 weeks. Severe vitamin B12 deficiency increased body fat% significantly, induced adiposity and altered lipid profile. Pregnant dams of both the deficient groups developed anemia. Severe vitamin B12 deficiency decreased the percentage of conception and litter size, pups were small-for-gestational-age and had significantly lower body weight at birth as well as weaning. Most of the offspring born to severely deficient dams died within 24 h of birth. Stress markers and adipocytokines were elevated in severe deficiency with concomitant decrease in antioxidant defense. The results show that severe but not moderate vitamin B12 restriction had profound impact on the physiology of C57BL/6 mice. Oxidative and corticosteroid stress, inflammation and poor antioxidant defense seem to be the probable underlying mechanisms mediating the deleterious effects. PMID- 26835455 TI - Within Patient Radiological Comparative Analysis of the Performance of Two Bone Graft Extenders Utilized in Posterolateral Lumbar Fusion: A Retrospective Case Series. AB - Two bone graft extenders differing in chemical composition were implanted contralaterally in 27 consecutive patients undergoing instrumented posterolateral lumbar fusion as standard-of-care. Bone marrow aspirate and autogenous bone graft were equally combined either with beta-tricalcium phosphate (beta-TCP) or a hybrid biomaterial [containing hyaluronic acid (HyA) but lacking a calcium salt] and implanted between the transverse processes. Fusion status on each side of the vertebrae was retrospectively graded (1-5 scale) on AP planar X-ray at multiple visits as available, through approximately 12 months. Additionally, consolidation or resorption since prior visit for each treatment was recorded. Sides receiving beta-TCP extender showed marked resorption prior to bone consolidation during the first 6 months. By contrast, sides receiving the hybrid biomaterial containing integrated HyA showed rapid bone consolidation by week 6-8, with maintenance of initial bone volume through 12 months. Fusion grade was superior for the hybrid biomaterial, differing significantly from beta-TCP at day 109 and beyond. Fusion success at >12 months was 92.9 vs. 67.9% for the hybrid biomaterial and beta-TCP treated sides, respectively. The hybrid biomaterial extender demonstrated a shortened time-to-fusion compared to the calcium-based graft. Mode of action has been demonstrated in the literature to differ between these compositions. Therefore, choice of synthetic biomaterial composition may significantly influence the mode of action of cellular events regulating appositional bone growth. PMID- 26835457 TI - A Case Report: Pseudoangiomatous Stromal Hyperplasia Tumor Presenting as a Palpable Mass. AB - We report a case of woman with a palpable lump on her left breast. On mammography, a huge mass located between the inner and the outer inferior breast quadrants of the left breast was found. The ultrasound examination realized later revealed a heterogeneous mass with smooth and lobulated borders. An MRI was also performed, showing an oval mass with heterogeneous areas of enhancement. Finally, a core biopsy under sonographic guidance revealed a pseudoangiomatous stromal hyperplasia of the breast. PMID- 26835456 TI - Breast Reconstruction after Mastectomy. AB - Breast cancer is the leading cause of cancer death in women worldwide. Its surgical approach has become less and less mutilating in the last decades. However, the overall number of breast reconstructions has significantly increased lately. Nowadays, breast reconstruction should be individualized at its best, first of all taking into consideration not only the oncological aspects of the tumor, neo-/adjuvant treatment, and genetic predisposition, but also its timing (immediate versus delayed breast reconstruction), as well as the patient's condition and wish. This article gives an overview over the various possibilities of breast reconstruction, including implant- and expander-based reconstruction, flap-based reconstruction (vascularized autologous tissue), the combination of implant and flap, reconstruction using non-vascularized autologous fat, as well as refinement surgery after breast reconstruction. PMID- 26835459 TI - A Proposed Method for Accurate 3D Analysis of Cochlear Implant Migration Using Fusion of Cone Beam CT. AB - INTRODUCTION: The goal of this investigation was to compare fusion of sequential cone beam computerized tomography (CT) volumes to the gold standard (fiducial registration) in order to be able to analyze clinical cochlear implant (CI) migration with high accuracy in three dimensions. MATERIALS AND METHODS: Paired cone beam CT volumes were performed on five human cadaver temporal bones and one human subject. These volumes were fused using 3D Slicer 4 and BRAINSFit software. Using a gold standard fiducial technique, the accuracy, robustness, and performance time of the fusion process were assessed. RESULTS: This proposed fusion protocol achieves a subvoxel median Euclidean distance of 0.05 mm in human cadaver temporal bones and 0.16 mm (mean) when applied to the described in vivo human synthetic data set in over 95% of all fusions. Performance times are <2 min. CONCLUSION: Here, a new and validated method based on existing techniques is described, which could be used to accurately quantify migration of CI electrodes. PMID- 26835458 TI - The - Not So - Solid 5.5 cm Threshold for Abdominal Aortic Aneurysm Repair: Facts, Misinterpretations, and Future Directions. AB - Abdominal aortic aneurysms (AAAs) represent a focal dilation of the aorta exceeding 1.5 times its normal diameter. It is reported that 4-8% of men and 0.5 1% of women above 50 years of age bear an AAA. Rupture represents the most disastrous complication of aneurysmal disease that is accompanied by an overall mortality of 80%. Autopsy data have shown that nearly 13% of AAAs with a maximum diameter <=5 cm were ruptured and 60% of the AAAs >5 cm in diameter never ruptured. It is therefore obvious that the "maximum diameter criterion," as a single parameter that fits all patients, is obsolete. Investigators have begun a search for more reliable rupture risk markers for AAA expansion, such as the level and change of peak wall stress or AAA geometry. Furthermore, it is becoming more and more evident that intraluminal thrombus (ILT), which is present in 75% of all AAAs, affects AAA features and promotes their expansion. Though these hemodynamic properties of AAAs are significant and seem to better describe rupture risk, they are in need of specialized equipment and software and demand time for processing making them difficult in use and unattractive to clinicians in everyday practice. In the search for the addition of other risk factors or user-friendly tools, which may predict AAA expansion and rupture, the use of the asymmetrical ILT deposition index seems appealing since it has been reported to identify AAAs that may have an increased or decreased growth rate. PMID- 26835460 TI - Comparison of Mesenchymal Stem Cell Surface Markers from Bone Marrow Aspirates and Adipose Stromal Vascular Fraction Sites. AB - The objective of this study was to subjectively evaluate the harvest of two areas of adipose collection and three areas of bone marrow collection as potential sites for clinical harvest of adipose stromal vascular fraction (SVF) and bone marrow concentrate for clinical use by quantifying the amount of tissue harvested, subjective ease of harvest, the variation of each site, and determining the cell surface marker characteristics using commercially available antibodies. Bone marrow and adipose tissue samples were collected from 10 adult mixed breed dogs. Adipose tissue was collected from the caudal scapular region and falciform fat ligament. Bone marrow aspirates were collected from the ilium, humerus, and tibia. Tissues were weighed (adipose) or measured by volume (bone marrow), processed to isolate the SVF or bone marrow concentrate, and flow cytometry was performed to quantitate the percentage of cells that were CD90, CD44 positive, and CD45 negative. Sites and tissue types were compared using matched pairs t-test. Subjectively subcutaneous fat collection was the most difficult and large amounts of tissue dissection were necessary. Additionally the subcutaneous area yielded less than the goal amount of tissue. The bone marrow harvest ranged from 10 to 27.5 ml. Adipose tissue had the highest concentration of cells with CD90(+), CD44(+), and CD45(-) markers (P < 0.05), and bone marrow had the highest total number of these cells at harvest (P < 0.05). Variation was high for all sites, but the adipose collection yielded more consistent results. These results describe the relative cellular components in the SVF of adipose tissue and bone marrow as defined by the biomarkers chosen. Although bone marrow yielded higher absolute cell numbers on average, adipose tissue yielded more consistent results. Fat from the falciform ligament was easily obtained with less dissection and therefore created less perceived relative patient trauma. PMID- 26835461 TI - Development of the Chick Microbiome: How Early Exposure Influences Future Microbial Diversity. AB - The concept of improving animal health through improved gut health has existed in food animal production for decades; however, only recently have we had the tools to identify microbes in the intestine associated with improved performance. Currently, little is known about how the avian microbiome develops or the factors that affect its composition. To begin to address this knowledge gap, the present study assessed the development of the cecal microbiome in chicks from hatch to 28 days of age with and without a live Salmonella vaccine and/or probiotic supplement; both are products intended to promote gut health. The microbiome of growing chicks develops rapidly from days 1-3, and the microbiome is primarily Enterobacteriaceae, but Firmicutes increase in abundance and taxonomic diversity starting around day 7. As the microbiome continues to develop, the influence of the treatments becomes stronger. Predicted metagenomic content suggests that, functionally, treatment may stimulate more differences at day 14, despite the strong taxonomic differences at day 28. These results demonstrate that these live microbial treatments do impact the development of the bacterial taxa found in the growing chicks; however, additional experiments are needed to understand the biochemical and functional consequences of these alterations. PMID- 26835462 TI - Nursing Students' Competencies in Evidence-Based Practice and Its Related Factors. AB - BACKGROUND: Evidence-Based Practice (EBP) is one of the nursing professional roles that can lead them to provide the best and more effective care. However, no studies are available on nursing students' competencies in EBP. OBJECTIVES: This study aimed to investigate the nursing students' knowledge, attitude and intention to implement EBP and its related factors in two nursing and midwifery faculties in Tehran, Iran. MATERIALS AND METHODS: In this cross-sectional study, 170 undergraduate nursing students were selected from two faculties of nursing and midwifery in Tehran, Iran. A census sampling method was applied and they were all before graduation in 2013. The Rubin and Parrish questionnaire was used to assess the students' knowledge, attitude and intention to implement EBP as well as factors affecting the implementation of EBP. Students completed the instrument through self-report. Descriptive statistics, Independent sample t-test and Pearson correlation coefficient were used to analyze the data. RESULTS: The students mean scores of knowledge, attitude and intention to implement EBP was 31.08 +/- 5.77, 50.40 +/- 9.58, 36.01 +/- 4.64, respectively. The students' age was inversely correlated with their scores of knowledge, attitude and intention to use EBP (P < 0.05). However, the students' GPA was in direct association with their knowledge, attitude and intention to implement EBP (P < 0.05). No significant differences were observed between the males and females mean scores in the three subscales. However, significant differences were found between the students mean scores in the two subscales of knowledge and attitudes toward EBP in terms of familiarity with statistics and research methods (P < 0.05). Neither familiarity with research methods nor familiarity with EBP could significantly affect the students' intention to implement EBP. CONCLUSIONS: The present study showed that nursing students have not a high mean score in the three subscales of knowledge, attitude and intention to implement EBP. It is essential for faculties and nurse managers not only to focus on education of EBP, but also to support nurses and nursing students to implement it in the process patient care. PMID- 26835463 TI - Effect of Using Eye Mask on Sleep Quality in Cardiac Patients: A Randomized Controlled Trial. AB - BACKGROUND: Patients in coronary care unit are at risk of sleep deprivation. Sleep deprivation can be associated with increased blood pressure and heart rate, raising the risk of developing cardiovascular problems among patients hospitalized in coronary care unit. OBJECTIVES: This study was carried out to examine the effect of eye mask on sleep quality in cardiac patients. PATIENTS AND METHODS: In this randomized controlled trial, 60 patients who met the inclusion criteria were selected using a convenient sampling method and randomly allocated into the experimental and control groups. Patients in the control group received routine care. However, in the experimental group, patients received routine care and eye mask for three subsequent nights. In the both groups, the sleep quality was assessed using the Pittsburgh sleep quality index. Data were analyzed by the chi-square test, independent samples t-test, Mann-Whitney U, and Wilcoxon signed rank tests. RESULTS: After the study, the median scores of the subjective sleep quality, the sleep latency, the sleep duration, the habitual sleep efficiency, and the sleep disturbances domains, as well as the median score of overall Pittsburgh sleep quality index in the experimental group were significantly lower than those in the control group (P < 0.05). However, no significant differences were observed between the two groups in terms of the use of sleep medications and the daytime dysfunction domains (P > 0.05). CONCLUSIONS: Using eye mask can significantly improve the sleep quality in cardiac patients. Therefore, nurses are recommended to use eye mask in combination with current treatments for improving patients' sleep quality. PMID- 26835464 TI - Developing a Questionnaire for Iranian Women's Attitude on Medical Ethics in Vaginal Childbirth. AB - BACKGROUND: Vaginal delivery is one of the challenging issues in medical ethics. It is important to use an appropriate instrument to assess medical ethics attitudes in normal delivery, but the lack of tool for this purpose is clear. OBJECTIVES: The aim of this study was to develop and validate a questionnaire for the assessment of women's attitude on medical ethics application in normal vaginal delivery. PATIENTS AND METHODS: This methodological study was carried out in Iran in 2013 - 2014. Medical ethics attitude in vaginal delivery questionnaire (MEAVDQ) was developed using the findings of a qualitative data obtained from a grounded theory research conducted on 20 women who had vaginal childbirth, in the first phase. Then, the validation criteria of this tool were tested by content and face validity in the second phase. Exploratory factor analysis was used for construct validity and reliability was also tested by Cronbach's alpha coefficient in the third phase of this study. SPSS version 13 was used in this study. The sample size for construct validity was 250 females who had normal vaginal childbirth. RESULTS: In the first phase of this study (tool development), by the use of four obtained categories and nine subcategories from grounded theory and literature review, three parts (98-items) of this tool were obtained (A, B and J). Part A explained the first principle of medical ethics, part B pointed to the second and third principles of medical ethics, and part J explained the fourth principle of medical ethics. After evaluating and confirming its face and content validity, 75 items remained in the questionnaire. In construct validity, by the employment of exploratory factor analysis, in parts A, B and J, 3, 7 and 3 factors were formed, respectively; and 62.8%, 64% and 51% of the total variances were explained by the obtained factors in parts A, B and J, respectively. The names of these factors in the three parts were achieved by consideration of the loading factor and medical ethics principles. The subscales of MEAVDQ showed significant reliability. In parts A, B and J, Cronbach's alpha coefficients were 0.76, 0.72 and 0.68, respectively and for the total questionnaire, it was 0.72. The results of the test-retest were satisfactory for all the items (ICC = 0.60 - 0.95). CONCLUSIONS: The present study showed that the 59-item MEAVDQ was a valid and reliable questionnaire for the assessment of women's attitudes toward medical ethics application in vaginal childbirth. This tool might assist specialists in making a judgment and plan appropriate for women in vaginal delivery management. PMID- 26835465 TI - Social Accountability in Nursing Education: A Necessary Yet Neglected Issue. PMID- 26835466 TI - The Effect of Massage With Lavender Oil on Restless Leg Syndrome in Hemodialysis Patients: A Randomized Controlled Trial. AB - BACKGROUND: Restless leg syndrome (RLS) is a common problem in patients with chronic renal failure. It can reduce the quality of life and sleep disturbances. This disorder is usually treated pharmacologically. Recently, complementary medicine methods have been suggested because of chemical drugs adverse effects. There is not enough evidence about the effect of aromatherapy on RLS. OBJECTIVES: The aim of this study was to determine the effects of massage with lavender oil on RLS symptoms in hemodialysis patients. PATIENTS AND METHODS: This randomized clinical trial study included 70 hemodialysis patients with RLS that were randomly assigned into two groups in 2014. The experimental group received effleurage massage using lavender oil and control group received routine care for three weeks. Data was collected with RLS questionnaire and analyzed using independent and paired t-test and Chi-square test. RESULTS: The mean RLS scores were not significantly different in the two groups at the start of study (22.41 +/- 7.67 vs. 22.90 +/- 4.38, P = 0.76). At the end of study, the mean RLS score significantly decreased in the intervention group, while this score remained relatively un-changed in the control group (12.41 +/- 5.49 vs. 23.23 +/- 4.52, P < 0.0001). CONCLUSIONS: Lavender oil massage was effective to improve RLS in hemodialysis patients. It has no adverse effects, is practical and cost effective. It is suggested to be used along with routine treatment of RLS in hemodialysis patients. PMID- 26835467 TI - Effect of Mindfulness-Based Stress Reduction on Anxiety, Depression and Stress in Women With Multiple Sclerosis. AB - BACKGROUND: Studies suggest that mindfulness-based interventions can improve anxiety, depression and stress in patients with multiple sclerosis (MS). However, no study investigated the effectiveness of this method in patients with a combination of problems such as depression, anxiety and stress simultaneously. However, comorbidities of depression and anxiety in MS are prevalent. OBJECTIVES: This study aimed to assess the effects of mindfulness-based stress reduction (MBRS) on anxiety, depression and stress in women with multiple sclerosis. PATIENTS AND METHODS: This randomized controlled clinical trial was performed in 2013 in Ahvaz MS Society. Forty eight patients were selected by convenient sampling and randomly assigned in experimental and control groups. The patients in the two groups filled out depression, anxiety and stress scale (DASS-21) at initiation of study, 8 weeks later and 1 month after the end of intervention. The experimental group received 8 sessions of MBRS, while the control group treated as usual. Finally, data of 40 patients analyzed using t-test, chi square and repeated measures analysis of variance. RESULTS: In the MBSR group, the mean depression, anxiety and stress were reduced significantly (P < 0.001). The mean depression score was 8.35 +/- 1.78 before the intervention and reduced to 4.80 +/ 0.83 and 4.45 +/- 0.60 after the intervention and follow-up (P < 0.001). Also the mean anxiety score was 8.90 +/- 1.97 before the intervention, which was significantly reduced to 4.70 +/- 1.38 and 4.55 +/- 0.99 after the intervention and follow-up (P < 0.001). The mean stress score was also 8.80 +/- 2.35 before treatment and 4.80 +/- 1.67 and 4.70 +/- 1.34 after the intervention and follow up (P < 0.001). CONCLUSIONS: This study showed that MBSR training can reduce mean depression, anxiety and stress scores in patients with MS. These findings suggest that MBSR is useful for psychological problems such as depression, anxiety and stress in patients with MS. PMID- 26835468 TI - Why Educators Should Apply Theories and Models of Health Education and Health Promotion to Teach Communication Skills to Nursing and Medical Students. PMID- 26835469 TI - E-learning for Critical Thinking: Using Nominal Focus Group Method to Inform Software Content and Design. AB - BACKGROUND: Undergraduate nursing students are often confused by multiple understandings of critical thinking. In response to this situation, the Critiique for critical thinking (CCT) project was implemented to provide consistent structured guidance about critical thinking. OBJECTIVES: This paper introduces Critiique software, describes initial validation of the content of this critical thinking tool and explores wider applications of the Critiique software. MATERIALS AND METHODS: Critiique is flexible, authorable software that guides students step-by-step through critical appraisal of research papers. The spelling of Critiique was deliberate, so as to acquire a unique web domain name and associated logo. The CCT project involved implementation of a modified nominal focus group process with academic staff working together to establish common understandings of critical thinking. Previous work established a consensus about critical thinking in nursing and provided a starting point for the focus groups. The study was conducted at an Australian university campus with the focus group guided by open ended questions. RESULTS: Focus group data established categories of content that academic staff identified as important for teaching critical thinking. This emerging focus group data was then used to inform modification of Critiique software so that students had access to consistent and structured guidance in relation to critical thinking and critical appraisal. CONCLUSIONS: The project succeeded in using focus group data from academics to inform software development while at the same time retaining the benefits of broader philosophical dimensions of critical thinking. PMID- 26835470 TI - Job Involvement and Organizational Commitment of Employees of Prehospital Emergency Medical System. AB - BACKGROUND: Several studies are available on organizational commitment of employees in different organizations. However, the organizational commitment and job involvement of the employees in the prehospital emergency medical system (PEMS) of Iran have largely been ignored. OBJECTIVES: This study aimed to investigate the organizational commitment and job involvement of the employees of PEMS and the relationship between these two issues. MATERIALS AND METHODS: This cross-sectional study was conducted on 160 employees of Kashan PEMS who were selected through a census method in 2014. A 3-part instrument was used in this study, including a demographic questionnaire, the Allen and Miller's organizational commitment inventory, and the Lodahl and Kejner's job involvement inventory. We used descriptive statistics, Spearman correlation coefficient, Kruskal-Wallis, Friedman, analysis of variance, and Tukey post hoc tests to analyze the data. RESULTS: The mean job involvement and organizational commitment scores were 61.78 +/- 10.69 and 73.89 +/- 13.58, respectively. The mean scores of job involvement and organizational commitment were significantly different in subjects with different work experiences (P = 0.043 and P = 0.012, respectively). However, no significant differences were observed between the mean scores of organizational commitment and job involvement in subjects with different fields of study, different levels of interest in the profession, and various educational levels. A direct significant correlation was found between the total scores of organizational commitment and job involvement of workers in Kashan PEMS (r = 0.910, P < 0.001). CONCLUSIONS: This study showed that the employees in the Kashan PEMS obtained half of the score of organizational commitment and about two thirds of the job involvement score. Therefore, the higher level managers of the emergency medical system are advised to implement some strategies to increase the employees' job involvement and organizational commitment. PMID- 26835471 TI - The Effect of Music on Anxiety and Cardiovascular Indices in Patients Undergoing Coronary Artery Bypass Graft: A Randomized Controlled Trial. AB - BACKGROUND: The instability of cardiovascular indices and anxiety disorders are common among patients undergoing coronary artery bypass graft (CABG) and could interfere with their recovery. Therefore, improving the cardiovascular indices and anxiety is essential. OBJECTIVES: This study aimed to investigate the effect of music therapy on anxiety and cardiovascular indices in patients undergoing CABG. PATIENTS AND METHODS: In this randomized controlled trial, 60 patients hospitalized in the cardiovascular surgical intensive care unit of Shahid Beheshti Hospital in Qom city, Iran, in 2013 were selected using a consecutive sampling method and randomly allocated into the experimental and control groups. In the experimental group, patients received 30 minutes of light music, whereas in the control group, patients had 30 minutes of rest in bed. The cardiovascular indices and anxiety were measured immediately before, immediately after and half an hour after the study. Data were analyzed using the chi-square test and repeated measures analysis of variance. RESULTS: Compared to the immediately before intervention, the mean anxiety scores immediately after and 30 minutes after the intervention were significantly lower in the experimental group (P < 0.037) while it did not significantly change in the control group. However, there were no significant differences regarding the cardiovascular indices in the three consecutive measurements (P > 0.05). CONCLUSIONS: Music therapy is effective in decreasing anxiety among patients undergoing CABG. However, the intervention was not effective on cardiovascular indices. Music can effectively be used as a non pharmacological method to manage anxiety after CABG. PMID- 26835472 TI - Scaffolds for Intracerebral Grafting of Neural Progenitor Cells After Cerebral Infarction: A Systematic Review. AB - CONTEXT: Intracerebral grafting of neural progenitor cells is a promising potential treatment to improve recovery after stroke, but the structural disruption and cavitation of brain tissue that occurs creates an unfavorable environment for graft cell survival. To overcome this obstacle, scaffold materials have been used as extracellular matrix to provide structural support for the transplanted cells. Many materials could potentially be used as scaffolds for this application. EVIDENCE ACQUISITION: We performed a systematic review to determine the available evidence supporting specific scaffolds for neural progenitor cell grafting after stroke. Articles were identified with a MeSH search on PubMed. Relevant references and "related articles" of selected manuscripts were also reviewed. Full original articles published prior to May 2013 presenting unique experimental data describing intracerebral grafting of neural progenitor cells in a scaffold after cerebral infarction were included in our study. All selected articles were reviewed thoroughly by the authors for relevant data. RESULTS: We found reports of use of scaffolds composed of polyglycolic acid, poly [lactic-co-glycolic acid] particles (with and without VEGF), hyaluronan-heparin-collagen hydrogel, Matrigel, collagen and extracellular matrix derived from porcine brain and urinary bladder. While multiple beneficial effects were reported, the optimal scaffold is unclear as we found no direct comparisons. CONCLUSIONS: We conclude that multiple scaffolds appear promising for neural progenitor cell grafting after stroke, but further research is needed to optimize this neurorestorative approach. Thus, we hope to provide a basic understanding of the state of scaffolds for neural progenitor cell grafting after stroke and to encourage further research. Based on the methods of the discussed studies, we propose a standardized set of outcomes that would best be used to evaluate and compare the effectiveness of a given scaffold. PMID- 26835473 TI - Acute Pancreatitis Caused By Mushroom Poisoning: A Report of Two Cases. AB - Of the more than 5000 species of mushrooms known, 100 types are toxic and approximately 10% of these toxic types can cause fatal toxicity. A type of mushroom called Amanita phalloides is responsible for 95% of toxic mushroom poisonings. In this article, we report 2 cases of mushroom poisonings caused by Lactarius volemus, known as Tirmit by the local people. The patient and his wife were admitted to the emergency room with abdominal pain, nausea, and vomiting 20 hours after consuming Lactarius volemus, an edible type of mushroom. The patients reported that they had been collecting this mushroom from the mountains and eating them for several years but had never developed any clinicopathology to date. Further examination of the patients revealed a very rare case of acute pancreatitis due to mushroom intoxication. The male patient was admitted to the intensive care unit while his wife was followed in the internal medicine service, because of her relative mild clinical symptoms. Both patients recovered without sequelae and were discharged. In this article, we aimed to emphasize that gastrointestinal symptoms are often observed in mushroom intoxications and can be confused with acute pancreatitis, thus leading to misdiagnosis of patients. Early diagnosis and appropriate treatment can improve patients' prognosis and prevent the development of complications. PMID- 26835474 TI - Occam's Razor Need Not Apply: A Case of Concurrent Cryptococcal Meningitis and Primary Central Nervous System Lymphoma in an Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Patient. PMID- 26835475 TI - End-Stage Liver Disease Is a Strong Predictor of Early Mortality in Cryptococcosis. AB - Background. Cryptococcosis in the setting of end-stage liver disease (ESLD) has been associated with high mortality. We sought to compare the outcome of cryptococcal disease in patients with ESLD to that of human immunodeficiency virus (HIV)-positive patients and to those patients without HIV or ESLD. Methods. We assembled a retrospective cohort of 232 consecutive cases of cryptococcosis in our institution, from 2002 to 2014, inclusively. We analyzed the cases for comorbidities, type of infection, and survival. Data were analyzed with t tests, Fishers Exact test, and Kaplan-Meyer analysis. Results. Twenty-five (10.8%) patients with cryptococcal infection had concomitant ESLD; of these, 5 (20%) presented with peritonitis. Most (17 of 25, 68%) did not have any other cause of immunocompromise that has been more classically associated with cryptococcosis. Patients with ESLD had a significantly higher mortality than HIV-positive patients and HIV-negative patients without ESLD (HIVNE) (80% vs 13.6% and 22.7%, respectively; P < .001). In addition, fatal outcome in ESLD patients occurred more rapidly than in HIVNE patients, with a median survival of 6 days (vs 17), despite a comparable time to diagnosis (6.2 vs 6.6 days). Conclusions. Cryptococcosis is an important morbidity in patients with ESLD. Patients with ESLD who are infected with Cryptococcus have a high and rapid mortality. This suggests that a high level of vigilance for cryptococcal infection should be kept in patients with ESLD. PMID- 26835477 TI - Listeria monocytogenes Endovascular Graft Infection. AB - Although best managed by surgical resection, we present a case of Listeria monocytogenes endovascular graft infection alternatively treated with graft retention and antibiotic induction followed by a lifelong suppressive course. The epidemiological, pathological, and clinical features of this unique entity are reviewed. PMID- 26835476 TI - The Effect of Rosuvastatin on Markers of Immune Activation in Treatment-Naive Human Immunodeficiency Virus-Patients. AB - Background. Immune activation has been implicated in the excess mortality in human immunodeficiency virus (HIV)-infected patients, due to cardiovascular diseases and malignancies. Statins may modulate this immune activation. We assessed the capacity of rosuvastatin to mitigate immune activation in treatment naive HIV-infected patients. Methods. In a randomized double-blind placebo controlled crossover study, we explored the effects of 8 weeks of rosuvastatin 20 mg in treatment-naive male HIV-infected patients (n = 28) on immune activation markers: neopterin, soluble Toll-like receptor (TLR)2, sTLR4, interleukin (IL)-6, IL-1Ra, IL-18, d-dimer, highly sensitive C-reactive protein, and CD38 and/or human leukocyte antigen-DR expression on T cells. Baseline data were compared with healthy male controls (n = 10). Furthermore, the effects of rosuvastatin on HIV-1 RNA, CD4/CD8 T-cell count, and low-density lipoprotein cholesterol were examined and side effects were registered. Results. T-cell activation levels were higher in patients than in controls. Patients had higher levels of circulating IL-18, sTLR2, and neopterin (all P < .01). Twenty patients completed the study. Rosuvastatin increased the CD4/CD8 T-cell ratio (P = .02). No effect on other markers was found. Conclusions. Patients infected with HIV had higher levels of circulating neopterin, IL-18, sTLR2, and T-cell activation markers. Rosuvastatin had a small but significant positive effect on CD4/CD8 T-cell ratio, but no influence on other markers of T-cell activation and innate immunity was identified (The Netherlands National Trial Register [NTR] NTR 2349, http://www.trialregister.nl/trialreg/index.asp). PMID- 26835478 TI - Mycobacterium marinum Infection After Exposure to Coal Mine Water. AB - Mycobacterium marinum infection has been historically associated with exposure to aquariums, swimming pools, fish, or other marine fauna. We present a case of M marinum left wrist tenosynovitis and elbow bursitis associated with a puncture injury and exposure to coal mine water in Illinois. PMID- 26835479 TI - Minocycline-Induced Cutaneous Hyperpigmentation in an Orthopedic Patient Population. AB - Background. The objectives of this study were to estimate the incidence and evaluate risk factors for development of minocycline-induced cutaneous hyperpigmentation in patients with orthopedic infections. Methods. Patients with orthopedic infections evaluated at Mayo Clinic (Rochester, MN) and treated with minocycline from 1 January 2002 to 31 December 2011 were retrospectively identified. Long-term minocycline suppression was defined as daily minocycline use for at least 3 months. A proportional hazards model was used to evaluate potential risk factors. Results. Of 291 patients receiving long-term minocycline suppression, 54% (156 of 291) developed hyperpigmentation after a mean follow-up of 4.8 years (range, 0.3-13.2 years); 88% involved blue-gray pigmentation of normal skin that appeared most commonly in the lower (75%) and upper extremities (44%). The mean duration of minocycline therapy before hyperpigmentation was 1.5 years (range, 0.1-9 years) with a mean cumulative dosage of 107.3 g (range, 8.6 657 g). Notable risk factors include a history of vitamin D deficiency (relative risk [RR], 6.29; 95% confidence interval [CI], 1.91-15.27; P = .0052), presence of a shoulder prosthesis (RR, 3.2; 95% CI, 1.23-6.56; P = .0062), noncirrhotic liver pathology (RR, 3.63; 95% CI, 1.11-8.75; P = .0359), and use of a concurrent medication also known to cause hyperpigmentation (RR, 4.75; 95% CI, 1.83-10.1; P = .0029). Conclusions. Hyperpigmentation associated with the use of long-term minocycline suppression in patients with orthopedic infections is common. PMID- 26835480 TI - Short separation regression improves statistical significance and better localizes the hemodynamic response obtained by near-infrared spectroscopy for tasks with differing autonomic responses. AB - Autonomic nervous system response is known to be highly task-dependent. The sensitivity of near-infrared spectroscopy (NIRS) measurements to superficial layers, particularly to the scalp, makes it highly susceptible to systemic physiological changes. Thus, one critical step in NIRS data processing is to remove the contribution of superficial layers to the NIRS signal and to obtain the actual brain response. This can be achieved using short separation channels that are sensitive only to the hemodynamics in the scalp. We investigated the contribution of hemodynamic fluctuations due to autonomous nervous system activation during various tasks. Our results provide clear demonstrations of the critical role of using short separation channels in NIRS measurements to disentangle differing autonomic responses from the brain activation signal of interest. PMID- 26835481 TI - Coupling of cerebral blood flow and oxygen consumption during hypothermia in newborn piglets as measured by time-resolved near-infrared spectroscopy: a pilot study. AB - Hypothermia (HT) is a potent neuroprotective therapy that is now widely used in following neurological emergencies, such as neonatal asphyxia. An important mechanism of HT-induced neuroprotection is attributed to the associated reduction in the cerebral metabolic rate of oxygen ([Formula: see text]). Since cerebral circulation and metabolism are tightly regulated, reduction in [Formula: see text] typically results in decreased cerebral blood flow (CBF); it is only under oxidative stress, e.g., hypoxia-ischemia, that oxygen extraction fraction (OEF) deviates from its basal value, which can lead to cerebral dysfunction. As such, it is critical to measure these key physiological parameters during therapeutic HT. This report investigates a noninvasive method of measuring the coupling of [Formula: see text] and CBF under HT and different anesthetic combinations of propofol/nitrous-oxide ([Formula: see text]) that may be used in clinical practice. Both CBF and [Formula: see text] decreased with decreasing temperature, but the OEF remained unchanged, which indicates a tight coupling of flow and metabolism under different anesthetics and over the mild HT temperature range (38 degrees C to 33 degrees C). PMID- 26835482 TI - Differential pathlength factor informs evoked stimulus response in a mouse model of Alzheimer's disease. AB - Baseline optical properties are typically assumed in calculating the differential pathlength factor (DPF) of mouse brains, a value used in the modified Beer Lambert law to characterize an evoked stimulus response. We used spatial frequency domain imaging to measure in vivo baseline optical properties in 20 month-old control ([Formula: see text]) and triple transgenic APP/PS1/tau (3xTg AD) ([Formula: see text]) mouse brains. Average [Formula: see text] for control and 3xTg-AD mice was [Formula: see text] and [Formula: see text], respectively, at 460 nm; and [Formula: see text] and [Formula: see text], respectively, at 530 nm. Average [Formula: see text] for control and 3xTg-AD mice was [Formula: see text] and [Formula: see text], respectively, at 460 nm; and [Formula: see text] and [Formula: see text], respectively, at 530 nm. The calculated DPF for control and 3xTg-AD mice was [Formula: see text] and [Formula: see text] OD mm, respectively, at 460 nm; and [Formula: see text] and [Formula: see text] OD mm, respectively, at 530 nm. In hindpaw stimulation experiments, the hemodynamic increase in brain tissue concentration of oxyhemoglobin was threefold larger and two times longer in the control mice compared to 3xTg-AD mice. Furthermore, the washout of deoxyhemoglobin from increased brain perfusion was seven times larger in controls compared to 3xTg-AD mice ([Formula: see text]). PMID- 26835483 TI - Hyperspectral optical tomography of intrinsic signals in the rat cortex. AB - We introduce a tomographic approach for three-dimensional imaging of evoked hemodynamic activity, using broadband illumination and diffuse optical tomography (DOT) image reconstruction. Changes in diffuse reflectance in the rat somatosensory cortex due to stimulation of a single whisker were imaged at a frame rate of 5 Hz using a hyperspectral image mapping spectrometer. In each frame, images in 38 wavelength bands from 484 to 652 nm were acquired simultaneously. For data analysis, we developed a hyperspectral DOT algorithm that used the Rytov approximation to quantify changes in tissue concentration of oxyhemoglobin ([Formula: see text]) and deoxyhemoglobin (ctHb) in three dimensions. Using this algorithm, the maximum changes in [Formula: see text] and ctHb were found to occur at [Formula: see text] and [Formula: see text] beneath the surface of the cortex, respectively. Rytov tomographic reconstructions revealed maximal spatially localized increases and decreases in [Formula: see text] and ctHb of [Formula: see text] and [Formula: see text], respectively, with these maximum changes occurring at [Formula: see text] poststimulus. The localized optical signals from the Rytov approximation were greater than those from modified Beer-Lambert, likely due in part to the inability of planar reflectance to account for partial volume effects. PMID- 26835485 TI - On the photovoltaic effect in local field potential recordings. AB - Optogenetics allows light activation of genetically defined cell populations and the study of their link to specific brain functions. While it is a powerful method that has revolutionized neuroscience in the last decade, the shortcomings of directly stimulating electrodes and living tissue with light have been poorly characterized. Here, we assessed the photovoltaic effects in local field potential (LFP) recordings of the mouse hippocampus. We found that light leads to several artifacts that resemble genuine LFP features in animals with no opsin expression, such as stereotyped peaks at the power spectrum, phase shifts across different recording channels, coupling between low and high oscillation frequencies, and sharp signal deflections that are detected as spikes. Further, we tested how light stimulation affected hippocampal LFP recordings in mice expressing channelrhodopsin 2 in parvalbumin neurons (PV/ChR2 mice). Genuine oscillatory activity at the frequency of light stimulation could not be separated from light-induced artifacts. In addition, light stimulation in PV/ChR2 mice led to an overall decrease in LFP power. Thus, genuine LFP changes caused by the stimulation of specific cell populations may be intermingled with spurious changes caused by photovoltaic effects. Our data suggest that care should be taken in the interpretation of electrophysiology experiments involving light stimulation. PMID- 26835484 TI - Review of optical coherence tomography based angiography in neuroscience. AB - The brain is a complex ecosystem, consisting of multiple layers and tissue compartments. To facilitate the understanding of its function and its response to neurological insults, a fast in vivo imaging tool with a micron-level resolution, which can provide a field of view at a few millimeters, is desirable. Optical coherence tomography (OCT) is a noninvasive method for imaging three-dimensional biological tissues with high resolution ([Formula: see text]) and without a need for contrast agents. Recent development of OCT-based angiography has started to shed some new light on cerebral hemodynamics in neuroscience. We give an overview of the recent developments of OCT-based imaging techniques for neuroscience applications in rodents. We summarize today's technological alternatives for OCT based angiography for neuroscience and provide a discussion of challenges and opportunities. Moreover, a summary of OCT angiography studies for stroke, traumatic brain injury, and subarachnoid hemorrhage cases on rodents is provided. PMID- 26835487 TI - Hybrid-modality ocular imaging using a clinical ultrasound system and nanosecond pulsed laser. AB - Hybrid optical modality imaging is a special type of multimodality imaging significantly used in the recent past in order to harness the strengths of different imaging methods as well as to furnish complementary information beyond that provided by any individual method. We present a hybrid-modality imaging system based on a commercial clinical ultrasound imaging (USI) system using a linear array ultrasound transducer (UST) and a tunable nanosecond pulsed laser as the source. The integrated system uses photoacoustic imaging (PAI) and USI for ocular imaging to provide the complementary absorption and structural information of the eye. In this system, B-mode images from PAI and USI are acquired at 10 Hz and about 40 Hz, respectively. A linear array UST makes the system much faster compared to other ocular imaging systems using a single-element UST to form B mode images. The results show that the proposed instrumentation is able to incorporate PAI and USI in a single setup. The feasibility and efficiency of this developed probe system was illustrated by using enucleated pig eyes as test samples. It was demonstrated that PAI could successfully capture photoacoustic signals from the iris, anterior lens surface, and posterior pole, while USI could accomplish the mapping of the eye to reveal the structures like the cornea, anterior chamber, lens, iris, and posterior pole. This system and the proposed methodology are expected to enable ocular disease diagnostic applications and can be used as a preclinical imaging system. PMID- 26835486 TI - Transcranial low-level laser therapy (810 nm) temporarily inhibits peripheral nociception: photoneuromodulation of glutamate receptors, prostatic acid phophatase, and adenosine triphosphate. AB - Photobiomodulation or low-level light therapy has been shown to attenuate both acute and chronic pain, but the mechanism of action is not well understood. In most cases, the light is applied to the painful area, but in the present study we applied light to the head. We found that transcranial laser therapy (TLT) applied to mouse head with specific parameters (810 nm laser, [Formula: see text], 7.2 or [Formula: see text]) decreased the reaction to pain in the foot evoked either by pressure (von Frey filaments), cold, or inflammation (formalin injection) or in the tail (evoked by heat). The pain threshold increasing is maximum around 2 h after TLT, remains up to 6 h, and is finished 24 h after TLT. The mechanisms were investigated by quantification of adenosine triphosphate (ATP), immunofluorescence, and hematoxylin and eosin (H&E) staining of brain tissues. TLT increased ATP and prostatic acid phosphatase (an endogenous analgesic) and reduced the amount of glutamate receptor (mediating a neurotransmitter responsible for conducting nociceptive information). There was no change in the concentration of tubulin, a constituent of the cytoskeleton, and the H&E staining revealed no tissue damage. This is the first study to show inhibition of peripheral pain due to photobiomodulation of the central nervous system. PMID- 26835488 TI - Automatic classification framework for ventricular septal defects: a pilot study on high-throughput mouse embryo cardiac phenotyping. AB - Intensive international efforts are underway toward phenotyping the entire mouse genome by modifying all its [Formula: see text] genes one-by-one for comparative studies. A workload of this scale has triggered numerous studies harnessing image informatics for the identification of morphological defects. However, existing work in this line primarily rests on abnormality detection via structural volumetrics between wild-type and gene-modified mice, which generally fails when the pathology involves no severe volume changes, such as ventricular septal defects (VSDs) in the heart. Furthermore, in embryo cardiac phenotyping, the lack of relevant work in embryonic heart segmentation, the limited availability of public atlases, and the general requirement of manual labor for the actual phenotype classification after abnormality detection, along with other limitations, have collectively restricted existing practices from meeting the high-throughput demands. This study proposes, to the best of our knowledge, the first fully automatic VSD classification framework in mouse embryo imaging. Our approach leverages a combination of atlas-based segmentation and snake evolution techniques to derive the segmentation of heart ventricles, where VSD classification is achieved by checking whether the left and right ventricles border or overlap with each other. A pilot study has validated our approach at a proof-of-concept level and achieved a classification accuracy of 100% through a series of empirical experiments on a database of 15 images. PMID- 26835489 TI - Developing a utility decision framework to evaluate predictive models in breast cancer risk estimation. AB - Combining imaging and genetic information to predict disease presence and progression is being codified into an emerging discipline called "radiogenomics." Optimal evaluation methodologies for radiogenomics have not been well established. We aim to develop a decision framework based on utility analysis to assess predictive models for breast cancer diagnosis. We garnered Gail risk factors, single nucleotide polymorphisms (SNPs), and mammographic features from a retrospective case-control study. We constructed three logistic regression models built on different sets of predictive features: (1) Gail, (2) Gail + Mammo, and (3) Gail + Mammo + SNP. Then we generated receiver operating characteristic (ROC) curves for three models. After we assigned utility values for each category of outcomes (true negatives, false positives, false negatives, and true positives), we pursued optimal operating points on ROC curves to achieve maximum expected utility of breast cancer diagnosis. We performed McNemar's test based on threshold levels at optimal operating points, and found that SNPs and mammographic features played a significant role in breast cancer risk estimation. Our study comprising utility analysis and McNemar's test provides a decision framework to evaluate predictive models in breast cancer risk estimation. PMID- 26835490 TI - Associating spatial diversity features of radiologically defined tumor habitats with epidermal growth factor receptor driver status and 12-month survival in glioblastoma: methods and preliminary investigation. AB - We analyzed the spatial diversity of tumor habitats, regions with distinctly different intensity characteristics of a tumor, using various measurements of habitat diversity within tumor regions. These features were then used for investigating the association with a 12-month survival status in glioblastoma (GBM) patients and for the identification of epidermal growth factor receptor (EGFR)-driven tumors. T1 postcontrast and T2 fluid attenuated inversion recovery images from 65 GBM patients were analyzed in this study. A total of 36 spatial diversity features were obtained based on pixel abundances within regions of interest. Performance in both the classification tasks was assessed using receiver operating characteristic (ROC) analysis. For association with 12-month overall survival, area under the ROC curve was 0.74 with confidence intervals [0.630 to 0.858]. The sensitivity and specificity at the optimal operating point ([Formula: see text]) on the ROC were 0.59 and 0.75, respectively. For the identification of EGFR-driven tumors, the area under the ROC curve (AUC) was 0.85 with confidence intervals [0.750 to 0.945]. The sensitivity and specificity at the optimal operating point ([Formula: see text]) on the ROC were 0.76 and 0.83, respectively. Our findings suggest that these spatial habitat diversity features are associated with these clinical characteristics and could be a useful prognostic tool for magnetic resonance imaging studies of patients with GBM. PMID- 26835491 TI - Prediction of clinical phenotypes in invasive breast carcinomas from the integration of radiomics and genomics data. AB - Genomic and radiomic imaging profiles of invasive breast carcinomas from The Cancer Genome Atlas and The Cancer Imaging Archive were integrated and a comprehensive analysis was conducted to predict clinical outcomes using the radiogenomic features. Variable selection via LASSO and logistic regression were used to select the most-predictive radiogenomic features for the clinical phenotypes, including pathological stage, lymph node metastasis, and status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Cross-validation with receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve (AUC) was employed as the prediction metric. Higher AUCs were obtained in the prediction of pathological stage, ER, and PR status than for lymph node metastasis and HER2 status. Overall, the prediction performances by genomics alone, radiomics alone, and combined radiogenomics features showed statistically significant correlations with clinical outcomes; however, improvement on the prediction performance by combining genomics and radiomics data was not found to be statistically significant, most likely due to the small sample size of 91 cancer cases with 38 radiomic features and 144 genomic features. PMID- 26835492 TI - Imaging texture analysis for automated prediction of lung cancer recurrence after stereotactic radiotherapy. AB - Benign radiation-induced lung injury (RILI) is not uncommon following stereotactic ablative radiotherapy (SABR) for lung cancer and can be difficult to differentiate from tumor recurrence on follow-up imaging. We previously showed the ability of computed tomography (CT) texture analysis to predict recurrence. The aim of this study was to evaluate and compare the accuracy of recurrence prediction using manual region-of-interest segmentation to that of a semiautomatic approach. We analyzed 22 patients treated for 24 lesions (11 recurrences, 13 RILI). Consolidative and ground-glass opacity (GGO) regions were manually delineated. The longest axial diameter of the consolidative region on each post-SABR CT image was measured. This line segment is routinely obtained as part of the clinical imaging workflow and was used as input to automatically delineate the consolidative region and subsequently derive a periconsolidative region to sample GGO tissue. Texture features were calculated, and at two to five months post-SABR, the entropy texture measure within the semiautomatic segmentations showed prediction accuracies [areas under the receiver operating characteristic curve (AUC): 0.70 to 0.73] similar to those of manual GGO segmentations (AUC: 0.64). After integration into the clinical workflow, this decision support system has the potential to support earlier salvage for patients with recurrence and fewer investigations of benign RILI. PMID- 26835493 TI - Model predictions for the wide-angle x-ray scatter signals of healthy and malignant breast duct biopsies. AB - Wide-angle x-ray scatter (WAXS) could potentially be used to diagnose ductal carcinoma in situ (DCIS) in breast biopsies. The regions of interest were assumed to consist of fibroglandular tissue and epithelial cells and the model assumed that biopsies with DCIS would have a higher concentration of the latter. The scattered number of photons from a 2-mm diameter column of tissue was simulated using a 110-kV beam and selectively added in terms of momentum transfer. For a 1 min exposure, specificities and sensitivities of unity were obtained for biopsies 2- to 20-mm thick. The impact of sample and tumor cell layer thicknesses was studied. For example, a biopsy erroneously estimated to be 8 mm would be correctly diagnosed if its actual thickness was between 7.3 and 8.7 mm. An 8-mm thick malignant biopsy can be correctly diagnosed provided the malignant cell layer thickness is [Formula: see text]. WAXS methods could become a diagnostic tool for DCIS within breast biopsies. PMID- 26835494 TI - Quantifying cross-scatter contamination in biplane fluoroscopy motion analysis systems. AB - Biplane fluoroscopy is used for dynamic in vivo three-dimensional motion analysis of various joints of the body. Cross-scatter between the two fluoroscopy systems may limit tracking accuracy. This study measured the magnitude and effects of cross-scatter in biplane fluoroscopic images. Four cylindrical phantoms of 4-, 6 , 8-, and 10-in. diameter were imaged at varying kVp levels to determine the cross-scatter fraction and contrast-to-noise ratio (CNR). Monte Carlo simulations quantified the effect of the gantry angle on the cross-scatter fraction. A cadaver foot with implanted beads was also imaged. The effect of cross-scatter on marker-based tracking accuracy was investigated. Results demonstrated that the cross-scatter fraction varied from 0.15 for the 4-in. cylinder to 0.89 for the 10 in. cylinder when averaged across kVp. The average change in CNR due to cross scatter ranged from 5% to 36% CNR decreases for the 4- and 10-in. cylinders, respectively. In simulations, the cross-scatter fraction increased with the gantry angle for the 8- and 10-in. cylinders. Cross-scatter significantly increased static-tracking error by 15%, 25%, and 38% for the 6-, 8-, and 10-in. phantoms, respectively, with no significant effect for the foot specimen. The results demonstrated submillimeter marker-based tracking for a range of phantom sizes, despite cross-scatter degradation. PMID- 26835495 TI - Optimization of beam quality for photon-counting spectral computed tomography in head imaging: simulation study. AB - Head computed tomography (CT) plays an important role in the comprehensive evaluation of acute stroke. Photon-counting spectral detectors, as promising candidates for use in the next generation of x-ray CT systems, allow for assigning more weight to low-energy x-rays that generally contain more contrast information. Most importantly, the spectral information can be utilized to decompose the original set of energy-selective images into several basis function images that are inherently free of beam-hardening artifacts, a potential advantage for further improving the diagnosis accuracy. We are developing a photon-counting spectral detector for CT applications. The purpose of this work is to determine the optimal beam quality for material decomposition in two head imaging cases: nonenhanced imaging and K-edge imaging. A cylindrical brain tissue of 16-cm diameter, coated by a 6-mm-thick bone layer and 2-mm-thick skin layer, was used as a head phantom. The imaging target was a 5-mm-thick blood vessel centered in the head phantom. In K-edge imaging, two contrast agents, iodine and gadolinium, with the same concentration ([Formula: see text]) were studied. Three parameters that affect beam quality were evaluated: kVp settings (50 to 130 kVp), filter materials ([Formula: see text] to 83), and filter thicknesses [0 to 2 half value layer (HVL)]. The image qualities resulting from the varying x-ray beams were compared in terms of two figures of merit (FOMs): squared signal-difference to-noise ratio normalized by brain dose ([Formula: see text]) and that normalized by skin dose ([Formula: see text]). For nonenhanced imaging, the results show that the use of the 120-kVp spectrum filtered by 2 HVL copper ([Formula: see text]) provides the best performance in both FOMs. When iodine is used in K-edge imaging, the optimal filter is 2 HVL iodine ([Formula: see text]) and the optimal kVps are 60 kVp in terms of [Formula: see text] and 75 kVp in terms of [Formula: see text]. A tradeoff of 65 kVp was proposed to lower the potential risk of skin injuries if a relatively long exposure time is necessarily performed in the iodinated imaging. In the case of gadolinium imaging, both SD and BD can be minimized at 120 kVp filtered with 2 HVL thulium ([Formula: see text]). The results also indicate that with the same concentration and their respective optimal spectrum, the values of [Formula: see text] and [Formula: see text] in gadolinium imaging are, respectively, around 3 and 10 times larger than those in iodine imaging. However, since gadolinium is used in much lower concentrations than iodine in the clinic, iodine may be a preferable candidate for K-edge imaging. PMID- 26835496 TI - Identifying quantitative imaging features of posterior fossa syndrome in longitudinal MRI. AB - Up to 25% of children who undergo brain tumor resection surgery in the posterior fossa develop posterior fossa syndrome (PFS). This syndrome is characterized by mutism and disturbance in speech. Our hypothesis is that there is a correlation between PFS and the occurrence of hypertrophic olivary degeneration (HOD) in structures within the posterior fossa, known as the inferior olivary nuclei (ION). HOD is exhibited as an increase in size and intensity of the ION on an MR image. Longitudinal MRI datasets of 28 patients were acquired consisting of pre-, intra-, and postoperative scans. A semiautomated segmentation process was used to segment the ION on each MR image. A full set of imaging features describing the first- and second-order statistics and size of the ION were extracted for each image. Feature selection techniques were used to identify the most relevant features among the MRI features, demographics, and data based on neuroradiological assessment. A support vector machine was used to analyze the discriminative features selected by a generative k-nearest neighbor algorithm. The results indicate the presence of hyperintensity in the left ION as the most diagnostically relevant feature, providing a statistically significant improvement in the classification of patients ([Formula: see text]) when using this feature alone. PMID- 26835497 TI - Implementation methods of medical image sharing for collaborative health care based on IHE XDS-I profile. AB - IHE XDS-I profile proposes an architecture model for cross-enterprise medical image sharing, but there are only a few clinical implementations reported. Here, we investigate three pilot studies based on the IHE XDS-I profile to see whether we can use this architecture as a foundation for image sharing solutions in a variety of health-care settings. The first pilot study was image sharing for cross-enterprise health care with federated integration, which was implemented in Huadong Hospital and Shanghai Sixth People's Hospital within the Shanghai Shen Kang Hospital Management Center; the second pilot study was XDS-I-based patient controlled image sharing solution, which was implemented by the Radiological Society of North America (RSNA) team in the USA; and the third pilot study was collaborative imaging diagnosis with electronic health-care record integration in regional health care, which was implemented in two districts in Shanghai. In order to support these pilot studies, we designed and developed new image access methods, components, and data models such as RAD-69/WADO hybrid image retrieval, RSNA clearinghouse, and extension of metadata definitions in both the submission set and the cross-enterprise document sharing (XDS) registry. We identified several key issues that impact the implementation of XDS-I in practical applications, and conclude that the IHE XDS-I profile is a theoretically good architecture and a useful foundation for medical image sharing solutions across multiple regional health-care providers. PMID- 26835498 TI - Determination of contrast media administration to achieve a targeted contrast enhancement in computed tomography. AB - Contrast enhancement is a key component of computed tomography (CT) imaging and offers opportunities for optimization. The design and optimization of techniques, however, require orchestration with the scan parameters and, further, a methodology to relate contrast enhancement and injection function. We used such a methodology to develop a method, the analytical inverse method, to predict the required injection function to achieve a desired contrast enhancement in a given organ by incorporation of a physiologically based compartmental model. The method was evaluated across 32 different target contrast enhancement functions for aorta, kidney, stomach, small intestine, and liver. The results exhibited that the analytical inverse method offers accurate performance with error in the range of 10% deviation between the predicted and desired organ enhancement curves. However, this method is incapable of predicting the injection function based on the liver enhancement. The findings of this study can be useful in optimizing contrast medium injection function as well as scan timing to provide more consistency in the way contrast-enhanced CT examinations are performed. To our knowledge, this work is one of the first attempts to predict the contrast material injection function for a desired organ enhancement curve. PMID- 26835499 TI - Two-dimensional dynamic fluid bowtie attenuators. AB - Fluence field modulated (FFM) CT allows for improvements in image quality and dose reduction. To date, only one-dimensional modulators have been proposed, as the extension to two-dimensional (2-D) modulation is difficult with solid-metal attenuation-based fluence field modulated designs. This work proposes to use liquid and gas to attenuate the x-ray beam, as unlike solids, these materials can be arranged allowing for 2-D fluence modulation. The thickness of liquid and the pressure for a given path length of gas were determined that provided the same attenuation as 30 cm of soft tissue at 80, 100, 120, and 140 kV. Liquid iodine, zinc chloride, cerium chloride, erbium oxide, iron oxide, and gadolinium chloride were studied. Gaseous xenon, uranium hexafluoride, tungsten hexafluoride, and nickel tetracarbonyl were also studied. Additionally, we performed a proof-of concept experiment using a 96 cell array in which the liquid thickness in each cell was adjusted manually. Liquid thickness varied as a function of kV and chemical composition, with erbium oxide allowing for the smallest thickness. For the gases, tungsten hexaflouride required the smallest pressure to compensate for 30 cm of soft tissue. The 96 cell iodine attenuator allowed for a reduction in both dynamic range to the detector and scatter-to-primary ratio. For both liquids and gases, when k-edges were located within the diagnostic energy range used for imaging, the mean beam energy exhibited the smallest change with compensation amount. The thickness of liquids and the gas pressure seem logistically implementable within the space constraints of C-arm-based cone beam CT (CBCT) and diagnostic CT systems. The gas pressures also seem logistically implementable within the space and tube loading constraints of CBCT and diagnostic CT systems. PMID- 26835500 TI - Volumetric limiting spatial resolution analysis of four-dimensional digital subtraction angiography. AB - C-Arm CT three-dimensional (3-D) digital subtraction angiography (DSA) reconstructions cannot provide temporal information to radiologists. Four dimensional (4-D) DSA provides a time series of 3-D volumes utilizing temporal dynamics in the two-dimensional (2-D) projections using a constraining image reconstruction approach. Volumetric limiting spatial resolution (VLSR) of 4-D DSA is quantified and compared to a 3-D DSA. The effects of varying 4-D DSA parameters of 2-D projection blurring kernel size and threshold of the 3-D DSA (constraining image) of an in silico phantom (ISPH) and physical phantom (PPH) were investigated. The PPH consisted of a 76-micron tungsten wire. An [Formula: see text] scan protocol acquired the projection data. VLSR was determined from MTF curves generated from each 2-D transverse slice of every (248) 4-D temporal frame. 4-D DSA results for PPH and ISPH were compared to the 3-D DSA. 3-D DSA analysis resulted in a VLSR of 2.28 and [Formula: see text] for ISPH and PPH, respectively. Kernel sizes of either [Formula: see text] or [Formula: see text] with a 3-D DSA constraining image threshold of 10% provided 4-D DSA VLSR nearest to the 3-D DSA. 4-D DSA yielded 2.21 and [Formula: see text] with a percent error of 3.1 and 1.2% for ISPH and PPH, respectively, as compared to 3-D DSA. This research indicates 4-D DSA is capable of retaining the resolution of 3-D DSA. PMID- 26835501 TI - Improved image reconstruction of low-resolution multichannel phase contrast angiography. AB - In low-resolution phase contrast magnetic resonance angiography, the maximum intensity projected channel images will be blurred with consequent loss of vascular details. The channel images are enhanced using a stabilized deblurring filter, applied to each channel prior to combining the individual channel images. The stabilized deblurring is obtained by the addition of a nonlocal regularization term to the reverse heat equation, referred to as nonlocally stabilized reverse diffusion filter. Unlike reverse diffusion filter, which is highly unstable and blows up noise, nonlocal stabilization enhances intensity projected parallel images uniformly. Application to multichannel vessel enhancement is illustrated using both volunteer data and simulated multichannel angiograms. Robustness of the filter applied to volunteer datasets is shown using statistically validated improvement in flow quantification. Improved performance in terms of preserving vascular structures and phased array reconstruction in both simulated and real data is demonstrated using structureness measure and contrast ratio. PMID- 26835502 TI - Quantitative analysis of ultrasound images for computer-aided diagnosis. AB - We propose an adaptable framework for analyzing ultrasound (US) images quantitatively to provide computer-aided diagnosis using machine learning. Our preliminary clinical targets are hepatic steatosis, adenomyosis, and craniosynostosis. For steatosis and adenomyosis, we collected US studies from 288 and 88 patients, respectively, as well as their biopsy or magnetic resonanceconfirmed diagnosis. Radiologists identified a region of interest (ROI) on each image. We filtered the US images for various texture responses and use the pixel intensity distribution within each ROI as feature parameterizations. Our craniosynostosis dataset consisted of 22 CT-confirmed cases and 22 age matched controls. One physician manually measured the vectors from the center of the skull to the outer cortex at every 10 deg for each image and we used the principal directions as shape features for parameterization. These parameters and the known diagnosis were used to train classifiers. Testing with cross validation, we obtained 72.74% accuracy and 0.71 area under receiver operating characteristics curve for steatosis ([Formula: see text]), 77.27% and 0.77 for adenomyosis ([Formula: see text]), and 88.63% and 0.89 for craniosynostosis ([Formula: see text]). Our framework is able to detect a variety of diseases with high accuracy. We hope to include it as a routinely available support system in the clinic. PMID- 26835503 TI - Accounting for anatomical noise in search-capable model observers for planar nuclear imaging. AB - Model observers intended to predict the diagnostic performance of human observers should account for the effects of both quantum and anatomical noise. We compared the abilities of several visual-search (VS) and scanning Hotelling-type models to account for anatomical noise in a localization receiver operating characteristic (LROC) study involving simulated nuclear medicine images. Our VS observer invoked a two-stage process of search and analysis. The images featured lesions in the prostate and pelvic lymph nodes. Lesion contrast and the geometric resolution and sensitivity of the imaging collimator were the study variables. A set of anthropomorphic mathematical phantoms was imaged with an analytic projector based on eight parallel-hole collimators with different sensitivity and resolution properties. The LROC study was conducted with human observers and the channelized nonprewhitening, channelized Hotelling (CH) and VS model observers. The CH observer was applied in a "background-known-statistically" protocol while the VS observer performed a quasi-background-known-exactly task. Both of these models were applied with and without internal noise in the decision variables. A perceptual search threshold was also tested with the VS observer. The model observers without inefficiencies failed to mimic the average performance trend for the humans. The CH and VS observers with internal noise matched the humans primarily at low collimator sensitivities. With both internal noise and the search threshold, the VS observer attained quantitative agreement with the human observers. Computational efficiency is an important advantage of the VS observer. PMID- 26835504 TI - In vivo effects of methamphetamine on brown fat reactive oxygen species and mitochondria. PMID- 26835505 TI - Quantitative assessments of glycolysis from single cells. AB - The most common positron emission tomography (PET) radio-labeled probe for molecular diagnostics in patient care and research is the glucose analog, 2-deoxy 2-[F-18]fluoro-D-glucose (18F-FDG). We report on an integrated microfluidics chip/beta particle imaging system for in vitro18F-FDG radioassays of glycolysis with single cell resolution. We investigated the kinetic responses of single glioblastoma cancer cells to targeted inhibitors of receptor tyrosine kinase signaling. Further, we find a weak positive correlation between cell size and rate of glycolysis. PMID- 26835507 TI - Using florbetapir positron emission tomography to explore cerebrospinal fluid cut points and gray zones in small sample sizes. AB - INTRODUCTION: We aimed to assess the feasibility of determining Alzheimer's disease cerebrospinal fluid (CSF) cut points in small samples through comparison with amyloid positron emission tomography (PET). METHODS: Twenty-three individuals (19 patients, four controls) had CSF measures of amyloid beta (Abeta)1-42 and total tau/Abeta1-42 ratio, and florbetapir PET. We compared CSF measures with visual and quantitative (standardized uptake value ratio [SUVR]) PET measures of amyloid. RESULTS: Seventeen of 23 were amyloid-positive on visual reads, and 14 of 23 at an SUVR of >=1.1. There was concordance (positive/negative on both measures) in 20 of 23, of whom 19 of 20 were correctly classified at an Abeta1-42 of 630 ng/L, and 20 of 20 on tau/Abeta1-42 ratio (positive >=0.88; negative <=0.34). Three discordant cases had Abeta1-42 levels between 403 and 729 ng/L and tau/Abeta1-42 ratios of 0.54-0.58. DISCUSSION: Comparing amyloid PET and CSF biomarkers provides a means of assessing CSF cut points in vivo, and can be applied to small sample sizes. CSF tau/Abeta1-42 ratio appears robust at predicting amyloid status, although there are gray zones where there remains diagnostic uncertainty. PMID- 26835508 TI - Insight into Best Variables for COPD Case Identification: A Random Forests Analysis. AB - RATIONALE: This study is part of a larger, multi-method project to develop a questionnaire for identifying undiagnosed cases of chronic obstructive pulmonary disease (COPD) in primary care settings, with specific interest in the detection of patients with moderate to severe airway obstruction or risk of exacerbation. OBJECTIVES: To examine 3 existing datasets for insight into key features of COPD that could be useful in the identification of undiagnosed COPD. METHODS: Random forests analyses were applied to the following databases: COPD Foundation Peak Flow Study Cohort (N=5761), Burden of Obstructive Lung Disease (BOLD) Kentucky site (N=508), and COPDGene(r) (N=10,214). Four scenarios were examined to find the best, smallest sets of variables that distinguished cases and controls:(1) moderate to severe COPD (forced expiratory volume in 1 second [FEV1] <50% predicted) versus no COPD; (2) undiagnosed versus diagnosed COPD; (3) COPD with and without exacerbation history; and (4) clinically significant COPD (FEV1<60% predicted or history of acute exacerbation) versus all others. RESULTS: From 4 to 8 variables were able to differentiate cases from controls, with sensitivity >=73 (range: 73-90) and specificity >68 (range: 68-93). Across scenarios, the best models included age, smoking status or history, symptoms (cough, wheeze, phlegm), general or breathing-related activity limitation, episodes of acute bronchitis, and/or missed work days and non-work activities due to breathing or health. CONCLUSIONS: Results provide insight into variables that should be considered during the development of candidate items for a new questionnaire to identify undiagnosed cases of clinically significant COPD. PMID- 26835509 TI - Gray Matter Features of Reading Disability: A Combined Meta-Analytic and Direct Analysis Approach(1,2,3,4). AB - Meta-analysis of voxel-based morphometry dyslexia studies and direct analysis of 293 reading disability and control cases from six different research sites were performed to characterize defining gray matter features of reading disability. These analyses demonstrated consistently lower gray matter volume in left posterior superior temporal sulcus/middle temporal gyrus regions and left orbitofrontal gyrus/pars orbitalis regions. Gray matter volume within both of these regions significantly predicted individual variation in reading comprehension after correcting for multiple comparisons. These regional gray matter differences were observed across published studies and in the multisite dataset after controlling for potential age and gender effects, and despite increased anatomical variance in the reading disability group, but were not significant after controlling for total gray matter volume. Thus, the orbitofrontal and posterior superior temporal sulcus gray matter findings are relatively reliable effects that appear to be dependent on cases with low total gray matter volume. The results are considered in the context of genetics studies linking orbitofrontal and superior temporal sulcus regions to alleles that confer risk for reading disability. PMID- 26835510 TI - Pleiotropic Control by Testosterone of a Learned Vocal Behavior and Its Underlying Neuroplasticity(1,2,3). AB - Steroid hormones coordinate multiple aspects of behavior and physiology. The same hormone often regulates different aspects of a single behavior and its underlying neuroplasticity. This pleiotropic regulation of behavior and physiology is not well understood. Here, we investigated the orchestration by testosterone (T) of birdsong and its neural substrate, the song control system. Male canaries were castrated and received stereotaxic implants filled with T in select brain areas. Implanting T solely in the medial preoptic nucleus (POM) increased the motivation to sing, but did not enhance aspects of song quality such as acoustic structure and stereotypy. In birds implanted with T solely in HVC (proper name), a key sensorimotor region of the song control system, little or no song was observed, similar to castrates that received no T implants of any sort. However, implanting T in HVC and POM simultaneously rescued all measures of song quality. Song amplitude, though, was still lower than what was observed in birds receiving peripheral T treatment. T in POM enhanced HVC volume bilaterally, likely due to activity-dependent changes resulting from an enhanced song rate. T directly in HVC, without increasing song rate, enhanced HVC volume on the ipsilateral side only. T in HVC enhanced the incorporation and recruitment of new neurons into this nucleus, while singing activity can independently influence the incorporation of new neurons into HVC. These results have broad implications for how steroid hormones integrate across different brain regions to coordinate complex social behaviors. PMID- 26835513 TI - Addiction Treatment in America: After Money or Aftercare? AB - There are approximately 14,500 clinics and programs in America that provide treatment for all types of addictive behaviors we call "Reward Deficiency Syndrome (RDS)". While most of these have good intentions to provide needed help to the victims of RDS, we propose herein that most of their efforts, especially during periods of aftercare, are not based on the existing scientific evidence. We use "aftercare" to refer to any form of program or therapy following primary treatment including 12-Step programs. Very few programs actually provide any evidenced-based treatment approaches during this most vulnerable period in recovery. In this trieste we are suggesting that a hypodopaminergic trait (genetic) and/or state (epigenetic) is critical in terms of continued motivation to use/abuse of alcohol or other drugs and can lead to relapse. While there is evidence for the approved FDA drugs to treat drug addiction (e.g. alcohol, opiates, nicotine) these drugs favor a short-term benefit by blocking dopamine. We argue instead for the utilization of long-term benefits that induce "dopamine homeostasis", or in simpler terms "normalcy". We suggest that this could be accomplished through a number of holistic modalities including, but not limited to, dopamine-boosting diets, hyper-oxygenation, heavy metal detoxification, exercise, meditation, yoga, and most importantly, brain neurotransmitter balancing with nutraceuticals such as KB220 variants. We embrace 12-step programs and fellowships but not as a stand-alone modality, especially during aftercare. We also provide some scientific basis for why resting state functional connectivity (rsfMRI) is so important and may be the cornerstone in terms of how to treat RDS. We postulate that since drugs, food, smoking, gambling, and even compulsive sexual behavior could reduce rsfMRI then modalities (following required research), that can restore this impaired cross talk between various brain regions (e.g. Nucleus accumbens, cingulate gyrus, hippocampus etc.) should be incorporated into the aftercare plan in all treatment programs in America. Anything less will ultimately lead to the so called "revolving door" for as many as 90% of treatment participants. PMID- 26835512 TI - HTLV-I Tax-Mediated Inactivation of Cell Cycle Checkpoints and DNA Repair Pathways Contribute to Cellular Transformation: "A Random Mutagenesis Model". AB - To achieve cellular transformation, most oncogenic retroviruses use transduction by proto-oncogene capture or insertional mutagenesis, whereby provirus integration disrupts expression of tumor suppressors or proto-oncogenes. In contrast, the Human T-cell leukemia virus type 1 (HTLV-I) has been classified in a separate class referred to as "transactivating retroviruses". Current views suggest that the viral encoded Tax protein transactivates expression of cellular genes leading to deregulated growth and transformation. However, if Tax-mediated transactivation was indeed sufficient for cellular transformation, a fairly high frequency of infected cells would eventually become transformed. In contrast, the frequency of transformation by HTLV-I is very low, likely less than 5%. This review will discuss the current understanding and recent discoveries highlighting critical functions of Tax in cellular transformation. HTLV-I Tax carries out essential functions in order to override cell cycle checkpoints and deregulate cellular division. In addition, Tax expression is associated with increased DNA damage and genome instability. Since Tax can inhibit multiple DNA repair pathways and stimulate unfaithful DNA repair or bypass checkpoints, these processes allow accumulation of genetic mutations in the host genome. Given this, a "Random Mutagenesis" transformation model seems more suitable to characterize the oncogenic activities of HTLV-I. PMID- 26835514 TI - Wake-up Strokes Are Similar to Known-Onset Morning Strokes in Severity and Outcome. AB - BACKGROUND: Stroke symptoms noticed upon waking, wake-up stroke, account for up to a quarter of all acute ischemic strokes. Patients with wake-up stroke, however, are often excluded from thrombolytic therapy. METHODS: Using our prospectively collected stroke registry, wake-up stroke and known-onset morning strokes were identified. Wakeup stroke was defined as a patient who was asleep >3 hours and first noted stroke symptoms upon awakening between 0100 and 1100. Known onset morning stroke was defined as a patient who had symptom onset while awake during the same time interval. We compared wake-up stoke to known-onset morning stroke with respect to patient demographics, stroke severity, etiology and outcomes. RESULTS: One-quarter of patients with acute ischemic strokes (391/1415) had documented time between 0100 and 1100 of symptom onset: 141 (36%) wake-up strokes and 250 (64%) known-onset morning strokes. No difference in baseline characteristics, stroke severity, stroke etiology, neurologic deterioration, discharge disposition or functional outcome was detected. Known-onset morning stroke patients were significantly more likely to get thrombolytic therapy and have higher risk of in-hospital mortality. Wake-up stroke patients tended to be older, have higher diastolic blood pressure and have longer length of hospital stay. DISCUSSION: While patients with wake-up stroke were similar to patients with known-onset morning stroke in many respects, patients with known onset morning stroke were significantly more likely to get treated with thrombolytic therapy and have higher in-hospital mortality. PMID- 26835515 TI - Serum Cotinine and Chronic Pain: NHANES 2003-2004. AB - PURPOSE: Tobacco smoke exposure continues to be the leading preventable risk factor for many diseases and has the potential to be a risk factor for chronic pain. The purpose of this study is to determine the relationship of chronic pain with smoking, secondhand smoke exposure and non-smoking using serum cotinine (and self-report of living with someone who smokes in the home) to identify the tobacco exposure groups. METHODS: The National Health and Nutrition Examination Survey (NHANES) 2003-2004 was used for this study. Participants were queried about pain duration and had serum cotinine levels determined during the course of the NHANES examination/survey. Participants, ages 20 years and above, with complete data on chronic pain, cotinine level, sex, race/ethnicity, and responses concerning living with someone who smoked in the home were included in the study (n=4429). RESULTS: The adjusted odds ratio of tobacco smoke exposure on chronic pain was 1.67 (95% CI: 1.08, 2.59; p=0.0220) for participants with a serum cotinine level >10 ng/mg (smokers) as compared with individuals who had a non detectable serum cotinine level. For individuals with a serum cotinine level >0.011 ng/mg to 10 ng/mg who identified as living with someone who smoked in the home, the adjusted odds ratio was 0.88 (95% CI: 0.47, 1.65; p=0.6785) as compared with individuals who had a non-detectable serum cotinine level. CONCLUSION: Chronic pain is a complex situation with many factors affecting it. Similarly, smoking is a complex addiction. The interplay of chronic pain and cotinine levels in this study were significant. PMID- 26835511 TI - The Zebrafish as a Tool to Cancer Drug Discovery. AB - The ability of zebrafish to faithfully recapitulate a variety of human cancers provides a unique in vivo system for drug identification and validation. Zebrafish models of human cancer generated through methodologies such as transgenesis, gene inactivation, transplantation, and carcinogenic induction have proven similar to their human counterparts both molecularly and pathologically. Suppression of cancer-relevant phenotypes provides opportunities to both identify and evaluate efficacious compounds using embryonic and adult zebrafish. After relevant compounds are selected, preclinical evaluation in mammalian models can occur, delivering lead compounds to human trials swiftly and rapidly. The advantages of in vivo imaging, large progeny, and rapid development that the zebrafish provides make it an attractive model to promote novel cancer drug discovery and reduce the hurdles and cost of clinical trials. This review explores the current methodologies to model human cancers in zebrafish, and how these cancer models have aided in formation of novel therapeutic hypotheses. PMID- 26835506 TI - Multifaceted signaling regulators of chondrogenesis: Implications in cartilage regeneration and tissue engineering. AB - Defects of articular cartilage present a unique clinical challenge due to its poor self-healing capacity and avascular nature. Current surgical treatment options do not ensure consistent regeneration of hyaline cartilage in favor of fibrous tissue. Here, we review the current understanding of the most important biological regulators of chondrogenesis and their interactions, to provide insight into potential applications for cartilage tissue engineering. These include various signaling pathways, including: fibroblast growth factors (FGFs), transforming growth factor beta (TGF-beta)/bone morphogenic proteins (BMPs), Wnt/beta-catenin, Hedgehog, Notch, hypoxia, and angiogenic signaling pathways. Transcriptional and epigenetic regulation of chondrogenesis will also be discussed. Advances in our understanding of these signaling pathways have led to promising advances in cartilage regeneration and tissue engineering. PMID- 26835518 TI - New cytotoxic cyclic peroxide acids from Plakortis sp. marine sponge. AB - Bioassay-guided fractionation of the extract of Jamaican marine sponge Plakortis sp. followed by preparative TLC and HPLC yielded several known methyl ester cyclic peroxides (1a, 2a, 3a, 4, 5), known plakortides (6,7), known bicyclic lactone (8) and new cyclic peroxide acids (1b, 2b, 3b). The chemical structures were elucidated by extensive interpretation of their spectroscopic data. These natural products showed remarkable in vitro cytotoxicity against several cancer cell lines. PMID- 26835519 TI - 86th Annual Georgia Public Health Association Meeting & Conference Report. AB - The 86th annual meeting of the Georgia Public Health Association (GPHA) and joint conference with the Southern Health Association was held in Atlanta, Georgia, on April 13-14, 2015, with pre-conference (April 12th) and post-conference (April 14th) Executive Board meetings. As Georgia's leading forum for public health researchers, practitioners, and students, the annual meeting of the GPHA brings together participants from across the state to explore recent developments in the field and to exchange techniques, tools, and experiences. Historically, the GPHA conference has been held in Savannah (n=24); Jekyll Island (n=20); Atlanta (n=16); Augusta (n=4); and Gainesville (n=1). There was no annual meeting during the early years (1929-1936); during World War II (1941-1943 and 1945); and for four years during the 1980s. Between 2006 and 2010, GPHA held one-day annual meetings and business sessions with educational workshops. Several new initiatives were highlighted as part of this year's conference. These included a "move and groove" physical activity lounge, registration scholarships for students with a dedicated meet-and-greet reception, an expanded exhibit hall, presentation and approval of three resolutions (related to healthy foods at official activities and events; weapons at official activities and events; and memorials), and approval of the 2015 legislative policy positions and amended association bylaws. The theme for the conference was Advocacy in Action for Public Health. Specifically, the program addressed ensuring access to care; protecting funding for core programs, services, and infrastructure; eliminating health disparities; and addressing key public health issues important to the state of Georgia. One hundred and nine (109) abstracts were submitted for peer review; 36 were accepted for poster and 40 for workshop presentations. Four plenary sessions with keynote speakers covered the intersection between advocacy and policy, Georgia's response to the Ebola crisis, palliative care, and essentials of advocacy in action for public health. Concurrent workshops focused on Board of Health training, public health accreditation, capacity building, collaboration, patient-centered outcomes, synthetic cannabinoid use, the HIV care continuum, use of data for informed decision making, environmental threats, organizational development, epidemiology, policy, and regulation. Thirty-two (32) awards were presented, including Lawmaker of the Year Award to Governor Nathan and First Lady Sandra Deal for their active and engaged role in promoting public health in Georgia; and the Sellers-McCroan Award to Commissioner Brenda Fitzgerald, Georgia Department of Public Health (DPH) State Health Officer, for her leadership of the Georgia Ebola Response Team and leadership of the newly formed department. The conference attracted 569 registrants primarily through pre registration (n=561) with limited onsite registration (n=8). For this year's conference, there was a significant increase in attendance (36%) and exhibitors (33%) relative to 2014. Of registrants reporting GPHA section participation, representation included: academic (5%); administration (10%); boards of health (13%); career development (15%); emergency preparedness (2%); epidemiology (5%); health education and promotion (2%); information technology (2%); maternal and child health (3%); medical/dental (3%); nursing (10%); nutrition (<1%); and other/no record (15%). There was 100% participation in the conference from the state's 18 public health districts. The conference evaluation completed by a representative sample of registrants indicated areas of potential improvement as: starting sessions on time, using electronic and social media for the conference agenda/syllabus, and decreasing workshop sessions to 45 minutes. Most rated the conference as "good" or "excellent." PMID- 26835516 TI - Markers of HIV reservoir size and immune activation after treatment in acute HIV infection with and without raltegravir and maraviroc intensification. AB - BACKGROUND: It is unclear whether intensification of standard highly active antiretroviral therapy (HAART) with entry and integrase inhibitors during acute HIV infection (AHI) could yield greater benefits in reducing markers for HIV reservoir size and immune activation. METHODS: Thai patients with Fiebig I-IV AHI were prospectively enrolled and offered treatment. They were randomised 1:1 to HAART (tenofovir/emtricitabine/efavirenz, n =31) or megaHAART, a standard regimen intensified by raltegravir/maraviroc (n =31), during the first 24 weeks of therapy. Participants were monitored at weeks 0, 2, 4, 8 and 12, then every 12 weeks. Frequencies of peripheral blood mononuclear cells (PBMCs) carrying HIV DNA (total, integrated and 2-LTR episomes), plasma C-reactive protein (CRP) concentrations, and frequencies of activated T cells were measured. Flexible sigmoidoscopy was performed in willing participants (n =25) at baseline, weeks 24 and 96, and proviral DNA and RNA were determined. RESULTS: Baseline characteristics were similar in the HAART and megaHAART arms. Median age was 28 years and 95% were men. Median CD4 cell count was 388 cells/mm3. HIV RNA was 5.6 log10 copies/mL. HIV RNA declined more rapidly in the first 4 weeks with megaHAART (median -3.3 log10) than HAART (-2.6 log10). Time to achieve HIV RNA <50 copies/mL was shorter with megaHAART (median 55 days) than HAART (83 days, P =0.04). Viral suppression rates after week 12 did not differ between arms, and overall, 97% achieved suppression by week 48. The frequency of cells harbouring total HIV DNA was similarly low after 96 weeks in both treatment arms (median of 7 and 4 copies/106 PBMCs in the megaHAART and HAART arms, respectively, P =0.41). At weeks 2 and 12, frequency of cells carrying 2-LTR circles were significantly higher with megaHAART (P =0.03). In the sigmoid colon, total HIV DNA and HIV RNA declined after treatment, with no differences between arms. The frequencies of cells with 2-LTR circles were also higher in the sigmoid colon at week 24 with megaHAART. Plasma levels of CRP and frequencies of CD4+ and CD8+ T cells expressing CD38 and HLA-DR or Ki67 were similar between arms. CONCLUSIONS: Intensification of standard HAART with raltegravir and maraviroc was not associated with either statistically significant reductions of markers of HIV reservoir size in blood and sigmoid colon or markers of immune activation in blood. PMID- 26835517 TI - Soluble CD163 and monocyte populations in response to antiretroviral therapy and in relationship with neuropsychological testing among HIV-infected children. AB - BACKGROUND: Monocytes play a central role in HIV neuropathogenesis, but there are limited data on monocyte subsets and markers of monocyte activation in perinatally HIV-infected children. OBJECTIVE: To determine the relationship between monocyte subsets, the sCD163 monocyte activation marker, and neuropsychological performance among perinatally HIV-infected children initiating antiretroviral therapy (ART). METHODS: ART-naive children from the PREDICT study were categorised into two groups: those on ART for >=24 weeks (ART group, n =201) and those untreated (no ART group, n =79). This analysis used data from the baseline and week 144 including sCD163 and frequencies of activated monocytes (CD14+/CD16+/HLA-DR+), perivascular monocytes (CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+), and neuropsychological testing scores: Verbal and Performance Intelligence Quotient (VIQ and PIQ), Beery Visuomotor Integration (VMI) and Children's Color Trails 2 (CT2). RESULTS: Baseline demographic and HIV disease parameters were similar between groups. The median age was 6 years, CD4 was 20% (620 cells/mm3), and HIV RNA was 4.8 log10. By week 144, the ART vs the no ART group had significantly higher CD4 (938 vs 552 cells/mm3) and lower HIV RNA (1.6 vs 4.38 log10 copies/mL, P <0.05). sCD163 declined in the ART vs no ART group (median changes -2533 vs -159 ng/mL, P <0.0001). Frequencies of all monocyte subsets declined in the treated but not the untreated group (P <0.05). Higher CD14+/CD16+/HLA-DR+ percentage was associated with higher VIQ, Beery VMI and CT2 scores. Higher percentages of CD14+/CD16+/CD163+ and CD14low/CD16+/CD163+ were associated with higher CT2 and VIQ, respectively. CONCLUSION: ART significantly reduced sCD163 levels and frequencies of activated and perivascular monocytes. Higher frequencies of these cells correlated with better neuropsychological performance suggesting a protective role of monocyte macrophage immune activation in perinatal HIV infection in terms of neuropsychological function. PMID- 26835521 TI - Editorial: "Many roads lead to Rome". PMID- 26835520 TI - Mid-Space-Independent Symmetric Data Term for Pairwise Deformable Image Registration. AB - Aligning a pair of images in a mid-space is a common approach to ensuring that deformable image registration is symmetric - that it does not depend on the arbitrary ordering of the input images. The results are, however, generally dependent on the choice of the mid-space. In particular, the set of possible solutions is typically affected by the constraints that are enforced on the two transformations (that deform the two images), which are to prevent the mid-space from drifting too far from the native image spaces. The use of an implicit atlas has been proposed to define the mid-space for pairwise registration. In this work, we show that by aligning the atlas to each image in the native image space, implicit-atlas-based pairwise registration can be made independent of the mid space, thereby eliminating the need for anti-drift constraints. We derive a new symmetric cost function that only depends on a single transformation morphing one image to the other, and validate it through diffeomorphic registration experiments on brain magnetic resonance images. PMID- 26835522 TI - Esthetic rehabilitation of a worn dentition with a minimally invasive prosthetic procedure (MIPP). AB - A minimally invasive prosthetic procedure (MIPP) for the esthetic rehabilitation of the complete arch advocates the preservation of enamel to optimize the adhesive bond of the luting agent to both the tooth surface and the etchable ceramic restoration. When esthetic rehabilitation of a worn dentition is required, a MIPP can be selected to reduce the biological cost of removing additional enamel tooth structure. The fundamental steps to achieve this goal are to: (1) increase the vertical dimension of occlusion (VDO); (2) reduce the thickness of the monolithic ceramic material; (3) preserve the enamel during tooth preparation; and (4) adhesively bond the etchable ceramic restorations. This article presents a comprehensive, minimally invasive prosthetic treatment approach for the esthetic rehabilitation of a severely worn dentition using a lithium disilicate all-ceramic material with partial and complete coverage restorations. PMID- 26835524 TI - The Simultaneous Modeling Technique: closing gaps in posteriors. AB - Direct posterior restorations represent a widespread procedure in daily practice. Occlusal layering is often considered a complex task, generally not predictable and often requiring several occlusal adjustments. Moreover, direct posterior restorations are time consuming, as many small increments must be applied and cured individually to control shrinkage stress. Several authors have proposed different material layering techniques for posteriors. The authors of this article propose a simplified approach, which primarily aims to help the clinician perform quick, simple, predictable, and natural-looking occlusal modeling, reducing the need for occlusal adjustments. PMID- 26835523 TI - CAD/CAM monolithic restorations and full-mouth adhesive rehabilitation to restore a patient with a past history of bulimia: the modified three-step technique. AB - Due to an increasing awareness about dental erosion, many clinicians would like to propose treatments even at the initial stages of the disease. However, when the loss of tooth structure is visible only to the professional eye, and it has not affected the esthetics of the smile, affected patients do not usually accept a full-mouth rehabilitation. Reducing the cost of the therapy, simplifying the clinical steps, and proposing noninvasive adhesive techniques may promote patient acceptance. In this article, the treatment of an ex-bulimic patient is illustrated. A modified approach of the three-step technique was followed. The patient completed the therapy in five short visits, including the initial one. No tooth preparation was required, no anesthesia was delivered, and the overall (clinical and laboratory) costs were kept low. At the end of the treatment, the patient was very satisfied from a biologic and functional point of view. PMID- 26835525 TI - Fatigue resistance and crack propensity of novel "super-closed" sandwich composite resin restorations in large MOD defects. AB - OBJECTIVES: To assess the influence of conventional glass ionomer cement (GIC) vs resin-modified GIC (RMGIC) as a base material for novel, super-closed sandwich restorations (SCSR) and its effect on shrinkage-induced crack propensity and in vitro accelerated fatigue resistance. METHODS: A standardized MOD slottype tooth preparation was applied to 30 extracted maxillary molars (5 mm depth/5 mm buccolingual width). A modified sandwich restoration was used, in which the enamel/dentin bonding agent was applied first (Optibond FL, Kerr), followed by a Ketac Molar (3M ESPE)(group KM, n = 15) or Fuji II LC (GC) (group FJ, n = 15) base, leaving 2 mm for composite resin material (Miris 2, Coltene-Whaledent). Shrinkageinduced enamel cracks were tracked with photography and transillumination. Samples were loaded until fracture or to a maximum of 185,000 cycles under isometric chewing (5 H z), starting with a load of 200 N (5,000 X), followed by stages of 400, 600, 800, 1,000, 1,200, and 1,400 N at a maximum of 30,000 X each. Groups were compared using the life table survival analysis (alpha = .008, Bonferroni method). RESULTS: Group FJ showed the highest survival rate (40% intact specimens) but did not differ from group KM (20%) or traditional direct restorations (13%, previous data). SCSR generated less shrinkage-induced cracks. Most failures were re-restorable (above the cementoenamel junction [CEJ]). CONCLUSIONS: Inclusion of GIC/RMGIC bases under large direct SCSRs does not affect their fatigue strength but tends to decrease the shrinkage-induced crack propensity. CLINICAL SIGNIFICANCE: The use of GIC/ RMGIC bases and the SCSR is an easy way to minimize polymerization shrinkage stress in large MOD defects without weakening the restoration. PMID- 26835526 TI - The Octagon Model: a clinical tool for assessing marginal tissue recession. AB - The Octagon Model is a clinical assessment tool designed to assess marginal tissue recession (MTR) and estimate the level of difficulty in achieving root coverage. It evaluates eight patient- and siterelated factors: patient's expectations, smoking status, width of keratinized tissue, absence/presence of cervical lesion, interproximal soft tissue/bone level, depth and width of recession defect, and buccal bone thickness. The model is presented in a three colored diagram to facilitate communication between clinicians and between clinicians and their patients, and to assist clinicians in optimizing treatment plans at both site and patient levels. PMID- 26835527 TI - Evaluation of reliability and validity of three dental color-matching devices. AB - PURPOSE: To assess the repeatability and accuracy of three dental color-matching devices under standardized and freehand measurement conditions. MATERIALS AND METHODS: Two shade guides (Vita Classical A1-D4, Vita; and Vita Toothguide 3D Master, Vita), and three color-matching devices (Easyshade, Vita; SpectroShade, MHT Optic Research; and ShadeVision, X-Rite) were used. Five shade tabs were selected from the Vita Classical A1-D4 (A2, A3.5, B1, C4, D3), and five from the Vita Toothguide 3D-Master (1M1, 2R1.5, 3M2, 4L2.5, 5M3) shade guides. Each shade tab was recorded 15 continuous, repeated times with each device under two different measurement conditions (standardized, and freehand). Both qualitative (color shade) and quantitative (L, a, and b) color characteristics were recorded. The color difference (DeltaE) of each recorded value with the known values of the shade tab was calculated. The repeatability of each device was evaluated by the coefficient of variance. The accuracy of each device was determined by comparing the recorded values with the known values of the reference shade tab (one sample t test; alpha = 0.05). The agreement between the recorded shade and the reference shade tab was calculated. The influence of the parameters (devices and conditions) on the parameter DeltaE was investigated (two-way ANOVA). Comparison of the devices was performed with Bonferroni pairwise post-hoc analysis. RESULTS: Under standardized conditions, repeatability of all three devices was very good, except for ShadeVision with Vita Classical A1-D4. Accuracy ranged from good to fair, depending on the device and the shade guide. Under freehand conditions, repeatability and accuracy for Easyshade and ShadeVision were negatively influenced, but not for SpectroShade, regardless of the shade guide. CONCLUSION: Based on the total of the color parameters assessed per device, SpectroShade was the most reliable of the three color-matching devices studied. PMID- 26835528 TI - Influence of personality on tooth shade selection. AB - PURPOSE: The harmonious shade matching of restorations with adjacent natural teeth is a prerequisite for a successful esthetic restoration. Color is a combined effect of the physical properties of an object, the light source, and the perception of the observer. The interpretation of color is influenced by both the physiological and psychological health of an individual. It is critical to understand the influence of an individual's psychological state on the shade selection procedure to achieve better shade matching and post-treatment patient counseling. The aim of this study was to evaluate the influence of personality on tooth shade selection capability. MATERIALS AND METHODS: Two porcelain fused to metal (PFM) discs were fabricated. A reference shade was determined using a spectrophotometer (Vita Easyshade, Vita). The personalities of volunteers were identified using a Myers- Briggs Type Indicator (MBTI) questionnaire. The volunteers visually identified the shade of the two PFM discs under a controlled light source. The mean color difference was determined between the visual and the spectrophotometer values. The data thus obtained was statistically analyzed with Kruskal-Wallis and post-hoc comparison tests to ascertain the difference between the groups. RESULTS: The groups that performed better in tooth shade selection were ENTJ (2.923 +/- 2.36), ISTJ (3.086 +/- 2.56), ENFJ (3.197 +/- 2.936), and ESTJ (3.431+/- 2.78). The groups INTP (9.383 +/- 3.30), ISTP (9.133 +/- 3.44), ISFP (8.737 +/- 2.81), and INTJ (8.480 +/- 3.35) showed poor tooth shade selection ability. The Kruskal- Wallis test showed lower mean rank for group ENTJ (89.75), followed by ISTJ (92.25), and ENFJ (94.80). CONCLUSION: Within the limitations of this study, it was concluded that there was a statistically significant difference between the different personalities with regard to tooth shade selection ability. PMID- 26835529 TI - Cynthia Donaldson Steele, RN, BSN, MPH. PMID- 26835531 TI - A longitudinal investigation of children internationally adopted at school age. AB - Most existing research on children adopted internationally has focused on those adopted as infants and toddlers. The current study longitudinally tracked several outcomes, including cognitive, behavioral, emotional, attachment, and family functioning, in 25 children who had been internationally adopted at school age (M = 7.7 years old at adoption, SD = 3.4, range = 4-15 years). We examined the incidence of clinically significant impairments, significant change in outcomes over the three study points, and variables that predicted outcomes over time. Clinically significant impairments in sustained attention, full-scale intelligence, reading, language, executive functioning, externalizing problems, and parenting stress were common, with language and executive functioning impairments present at higher levels in the current study compared with past research focusing on children adopted as infants and toddlers. Over the three study points, significant improvements across most cognitive areas and attachment functioning were observed, though significant worsening in executive functioning and internalizing problems was present. Adoptive family-specific variables, such as greater maternal education, smaller family size, a parenting approach that encouraged age-expected behaviors, home schooling, and being the sole adopted child in the family were associated with greater improvement across several cognitive outcomes. In contrast, decreased parenting stress was predicted by having multiple adopted children and smaller family sizes were associated with greater difficulties with executive functioning. Child-specific variables were also linked to outcomes, with girls displaying worse attachment and poorer cognitive performance and with less time in orphanage care resulting in greater adoption success. Implications for future research and clinical applications are discussed. PMID- 26835532 TI - Event rate and reaction time performance in ADHD: Testing predictions from the state regulation deficit hypothesis using an ex-Gaussian model. AB - According to the state regulation deficit (SRD) account, ADHD is associated with a problem using effort to maintain an optimal activation state under demanding task settings such as very fast or very slow event rates. This leads to a prediction of disrupted performance at event rate extremes reflected in higher Gaussian response variability that is a putative marker of activation during motor preparation. In the current study, we tested this hypothesis using ex Gaussian modeling, which distinguishes Gaussian from non-Gaussian variability. Twenty-five children with ADHD and 29 typically developing controls performed a simple Go/No-Go task under four different event-rate conditions. There was an accentuated quadratic relationship between event rate and Gaussian variability in the ADHD group compared to the controls. The children with ADHD had greater Gaussian variability at very fast and very slow event rates but not at moderate event rates. The results provide evidence for the SRD account of ADHD. However, given that this effect did not explain all group differences (some of which were independent of event rate) other cognitive and/or motivational processes are also likely implicated in ADHD performance deficits. PMID- 26835533 TI - [Molecular epidemiology in healthcare-associated infections: guidelines of the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI)]. PMID- 26835534 TI - Author's Response. PMID- 26835535 TI - Retraction: Zheng L. et al. An Epidemiological Study of Risk Factors of Thyroid Nodule and Goiter in Chinese Women. Int. J. Environ. Res. Public Health 2015, 12, 11608-11620. PMID- 26835536 TI - C-Terminal Fragment, Abeta32-37, Analogues Protect Against Abeta Aggregation Induced Toxicity. AB - Amyloid-beta aggregation is a major etiological phenomenon in Alzheimer's disease. Herein, we report peptide-based inhibitors that diminish the amyloid load by obviating Abeta aggregation. Taking the hexapeptide fragment, Abeta32-37, as lead, more than 40 new peptides were synthesized. Upon evaluation of the newly synthesized hexapeptides as inhibitors of Abeta toxicity by the MTT-based cell viability assay, a number of peptides exhibited significant Abeta aggregation inhibitory activity at sub-micromolar concentration range. A hexapeptide (1) showed complete mitigation of Abeta toxicity in the cell culture assay at 2 MUM. In the ThT fluorescence assay, upon incubation of Abeta with this peptide, we observed no increase in the ThT fluorescence relative to control. The secondary structure estimation by circular dichroism spectroscopy and morphological examination by transmission electron microscopy further confirmed the results. PMID- 26835537 TI - Decreasing CNPY2 Expression Diminishes Colorectal Tumor Growth and Development through Activation of p53 Pathway. AB - Neovascularization drives tumor development, and angiogenic factors are important neovascularization initiators. We recently identified the secreted angiogenic factor CNPY2, but its involvement in cancer has not been explored. Herein, we investigate CNPY2's role in human colorectal cancer (CRC) development. Tumor samples were obtained from CRC patients undergoing surgery. Canopy 2 (CNPY2) expression was analyzed in tumor and adjacent normal tissue. Stable lines of human HCT116 cells expressing CNPY2 shRNA or control shRNA were established. To determine CNPY2's effects on tumor xenografts in vivo, human CNPY2 shRNA HCT116 cells and controls were injected into nude mice, separately. Cellular apoptosis, growth, and angiogenesis in the xenografts were evaluated. CNPY2 expression was significantly higher in CRC tissues. CNPY2 knockdown in HCT116 cells inhibited growth and migration and promoted apoptosis. In xenografts, CNPY2 knockdown prevented tumor growth and angiogenesis and promoted apoptosis. Knockdown of CNPY2 in the HCT116 CRC cell line reversibly increased p53 activity. The p53 activation increased cyclin-dependent kinase inhibitor p21 and decreased cyclin dependent kinase 2, thereby inhibiting tumor cell growth, inducing cell apoptosis, and reducing angiogenesis both in vitro and in vivo. CNPY2 may play a critical role in CRC development by enhancing cell proliferation, migration, and angiogenesis and by inhibiting apoptosis through negative regulation of the p53 pathway. Therefore, CNPY2 may represent a novel CRC therapeutic target and prognostic indicator. PMID- 26835538 TI - Murine Models of Acute Alcoholic Hepatitis and Their Relevance to Human Disease. AB - Alcohol-induced liver damage is a major burden for most societies, and murine studies can provide a means to better understand its pathogenesis and test new therapies. However, there are many models reported with widely differing phenotypes, not all of which fully regenerate the spectrum of human disease. Thus, it is important to understand the implications of these variations to efficiently model human disease. This review critically appraises key articles in the field, detailing the spectrum of liver damage seen in different models, and how they relate to the phenotype of disease seen in patients. A range of different methods of alcohol administration have been studied, ranging from ad libitum consumption of alcohol and water to modified diets (eg, Lieber deCarli liquid diet). Other feeding regimens have taken more invasive routes using intragastric feeding tubes to infuse alcohol directly into the stomach. Notably, models using wild-type mice generally produce a milder phenotype of liver damage than those using genetically modified mice, with the exception of the chronic binge-feeding model. We recommend panels of tests for consideration to standardize end points for the evaluation of the severity of liver damage-key for comparison of models of injury, testing of new therapies, and subsequent translation of findings into clinical practice. PMID- 26835540 TI - Urea-induced denaturation of human calcium/calmodulin-dependent protein kinase IV: a combined spectroscopic and MD simulation studies. AB - Calcium/calmodulin-dependent protein kinase IV (CaMKIV) is a multifunctional enzyme which belongs to the Ser/Thr kinase family. CaMKIV plays important role in varieties of biological processes such as gene expression regulation, memory consolidation, bone growth, T-cell maturation, sperm motility, regulation of microtubule dynamics, cell-cycle progression, and apoptosis. To measure stability parameters, urea-induced denaturation of CaMKIV was carried out at pH 7.4 and 25 degrees C, using three different probes, namely far-UV CD, near-UV absorption, and tryptophan fluorescence. A coincidence of normalized denaturation curves of these optical properties suggests that urea-induced denaturation is a two-state process. Analysis of these denaturation curves gave values of 4.20 +/- 0.12 kcal mol-1, 2.95 +/- 0.15 M, and 1.42 +/- 0.06 kcal mol-1 M-1 for [Formula: see text] (Gibbs free energy change (DeltaGD) in the absence of urea), Cm (molar urea concentration ([urea]) at the midpoint of the denaturation curve), and m (=?DeltaGD/?[urea]), respectively. All these experimental observations have been fully supported by 30 ns molecular dynamics simulation studies. PMID- 26835539 TI - A Statistical Approach Reveals Designs for the Most Robust Stochastic Gene Oscillators. AB - The engineering of transcriptional networks presents many challenges due to the inherent uncertainty in the system structure, changing cellular context, and stochasticity in the governing dynamics. One approach to address these problems is to design and build systems that can function across a range of conditions; that is they are robust to uncertainty in their constituent components. Here we examine the parametric robustness landscape of transcriptional oscillators, which underlie many important processes such as circadian rhythms and the cell cycle, plus also serve as a model for the engineering of complex and emergent phenomena. The central questions that we address are: Can we build genetic oscillators that are more robust than those already constructed? Can we make genetic oscillators arbitrarily robust? These questions are technically challenging due to the large model and parameter spaces that must be efficiently explored. Here we use a measure of robustness that coincides with the Bayesian model evidence, combined with an efficient Monte Carlo method to traverse model space and concentrate on regions of high robustness, which enables the accurate evaluation of the relative robustness of gene network models governed by stochastic dynamics. We report the most robust two and three gene oscillator systems, plus examine how the number of interactions, the presence of autoregulation, and degradation of mRNA and protein affects the frequency, amplitude, and robustness of transcriptional oscillators. We also find that there is a limit to parametric robustness, beyond which there is nothing to be gained by adding additional feedback. Importantly, we provide predictions on new oscillator systems that can be constructed to verify the theory and advance design and modeling approaches to systems and synthetic biology. PMID- 26835541 TI - Facile Fabrication of Multifunctional Hybrid Silk Fabrics with Controllable Surface Wettability and Laundering Durability. AB - To obtain a hydrophobic surface, TiO2 coatings are deposited on the surface of silk fabric using atomic layer deposition (ALD) to realize a hierarchical roughness structure. The surface morphology and topography, structure, and wettability properties of bare silk fabric and TiO2-coated silk fabrics thus prepared are evaluated using scanning electron microscopy (SEM), field-emission scanning electron microscopy (FESEM), scanning probe microscope (SPM), X-ray diffraction (XRD), static water contact angles (WCAs), and roll-off angles, respectively. The surfaces of the silk fabrics with the TiO2 coatings exhibit higher surface roughnesses compared with those of the bare silk fabric. Importantly, the hydrophobic and laundering durability properties of the TiO2 coated silk fabrics are largely improved by increasing the thickness of the ALD TiO2 coating. Meanwhile, the ALD process has a litter effect on the service performance of silk fabric. Overall, TiO2 coating using an ALD process is recognized as a promising approach to produce hydrophobic surfaces for elastic materials. PMID- 26835542 TI - Cervical Length and Androgens in Pregnant Women With Polycystic Ovary Syndrome: Has Metformin Any Effect? AB - CONTEXT: Women with polycystic ovary syndrome (PCOS) have increased risk of preterm delivery. Shortening of the cervix is a sign of preterm delivery. OBJECTIVE: This study aimed to investigate potential effect of metformin on cervical length and whether androgen levels correlate with cervical length in PCOS pregnancies. DESIGN AND SETTING: This was a sub-study of a randomized, placebo-controlled, multicenter study (The PregMet study) performed at 11 secondary or tertiary centers from 2005 to 2009. PARTICIPANTS: Two-hundred sixty one pregnancies of 245 women with PCOS, age 18-42 years participated. INTERVENTIONS: Participants were randomly assigned to metformin or placebo from first trimester to delivery. OUTCOME MEASUREMENTS: We compared cervical length and androgen levels in metformin and placebo groups at gestational weeks 19 and 32. We also explored whether cervical length correlated with androgen levels. RESULTS: We found no difference in cervical length between the metformin and the placebo groups at gestational week 19 and 32. Dehydroepiandrosterone (DHEAS) tended to be higher in the metformin group. There were no correlations between androgens and cervical length at week 19. At gestational week 32, androstenedione (P = .02) and DHEAS (P = .03) showed a trend toward negative correlation to cervical length. High androstenedione level correlated with shortening of cervical length from week 19 to 32 when adjusted for confounders (P = .003). T (P = .03), DHEAS (P = .02), and free testosterone index (P = .03) showed a similar trend. CONCLUSION: Metformin in pregnancy did not affect cervical length in women with PCOS. High maternal androgen levels correlated with cervical shortening from the second to the third trimester of pregnancy, as a sign of cervical ripening. PMID- 26835543 TI - ApoA-II HDL Catabolism and Its Relationships With the Kinetics of ApoA-I HDL and of VLDL1, in Abdominal Obesity. AB - We study the associations between apoA-II fractional catabolic rate (FCR) and the kinetics of VLDL subspecies and apoA-I and show that, in abdominally obese individuals, apoA-II FCR is positively and independently associated with both apoA-I FCR and VLDL1-TG indirect FCR. PMID- 26835545 TI - Generation, Characterization, and Application of Hierarchically Structured Self Assembly Induced by the Combined Effect of Self-Emulsification and Phase Separation. AB - Hierarchically structured magnetic single-hole hollow spheres (MSHS) have been successfully obtained via a facile self-assembly strategy. This methodology allows the double emulsions generated via the combined effect of self emulsification and phase separation to provide confinement for directing the self assembly of magnetic nanoparticles (MNPs). The resulting MSHS fully capitalize on both the multifunctional properties of MNPs and container features of single-hole hollow spheres. Moreover, the magnetic properties showed obvious improvement and can be tuned by modulating the assembled structure. Thus, MSHS can be used as a smart platform with multiple functionalities including image contrast enhancement, selective encapsulation for biomacromolecules, on-demand release, and magnetically guided transport. This strategy is very promising in the design of hierarchically structured assemblies for desired applications in biomedicine and other fields. PMID- 26835544 TI - Subclonality for BRAF Mutation in Papillary Thyroid Carcinoma Is Associated With Earlier Disease Stage. AB - CONTEXT: The presence of driver mutations only in a subset of tumor cells within a single lesion, defined as subclonality, is being appreciated as a clinically significant factor. BRAF mutation is the most common driver mutation in papillary thyroid carcinoma (PTC). There are conflicting data in the literature regarding the presence of BRAF mutation subclonality in PTC and its clinical significance. OBJECTIVE: The purpose of the present study was to use a molecular and morphometric approach to determine BRAF clonality status and its clinical pathological correlates. DESIGN: Fifty-nine cases of PTC were studied. DNA extracted from the tumors underwent deep sequencing to determine the percentage of BRAF mutant allele copies. Additionally, we used computerized morphometry to determine the fraction of tumor cells in each sample. Using both variables, we were able to determine the presence or absence of subclonality for BRAF mutation, which was further correlated with clinical, pathological, and prognostic data. RESULTS: BRAF mutation was found in 49 (83%) cases. The average percentage of tumor cells and of BRAF mutant alleles in the samples were 68.1 +/- 9.8 and 26 +/ 6.7, respectively. Based on the molecular and morphometric analysis, 11 (24%) cases were found to be subclonal for BRAF mutation. Tumors with subclonal BRAF mutations were significantly smaller compared to tumors with clonal mutation (0.82 +/- 0.38 cm vs 1.37 +/- 0.57 cm, P = .005) and were less likely to have lymph node metastasis (0% vs 32%, P = .03). CONCLUSIONS: In PTC, subclonality for BRAF mutation is associated with earlier stage. Molecular-morphometric analysis of PTC can provide clonality information with potential clinical significance. PMID- 26835546 TI - Molecular Insights into the Adsorption Mechanism of Human beta-Defensin-3 on Bacterial Membranes. AB - Human beta-defensin-3 (hBD3) is an endogenous antimicrobial peptide that exhibits broad-spectrum antibacterial activity without eukaryotic cytotoxicity. In this work, we carried out molecular dynamics (MD) simulations to explore its adsorption mechanism on, and the structural and thermodynamic contributions of individual residues to its antibacterial activity with both Gram-negative (GN) and Gram-positive (GP) bacterial membrane. Due to the strong electrostatic interaction of hBD3 with POPG lipids, which are more prevalent on the GP membrane, its adhesion to the GP membrane is stronger than to the GN membrane and stabilized more rapidly. On the surface of both bacterial membranes, the orientation of hBD3 is dominated by an electric dipole. We next analyzed the binding free energy decompositions of the hBD3-membrane complex using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method. The results of both the GN and the GP membrane simulations show that Arg17, Arg36, and Arg38 form both polar and nonpolar interactions and are potentially the key residues for hBD3 antibacterial activity. On the other hand, there was a significant difference in the energy contribution of Arg12 between the GP and GN membrane simulations, suggesting that Arg12 is a key factor in the toxicity of hBD3 to specifically GP bacteria. Our findings shed light on the antibacterial activity of hBD3 on bacterial membranes and yield insights useful for the design of potent antimicrobial peptides targeting multidrug resistant bacteria. PMID- 26835547 TI - Validation of the Microsoft Kinect(r) camera system for measurement of lower extremity jump landing and squatting kinematics. AB - Cost effective, quantifiable assessment of lower extremity movement represents potential improvement over standard tools for evaluation of injury risk. Ten healthy participants completed three trials of a drop jump, overhead squat, and single leg squat task. Peak hip and knee kinematics were assessed using an 8 camera BTS Smart 7000DX motion analysis system and the Microsoft Kinect(r) camera system. The agreement and consistency between both uncorrected and correct Kinect kinematic variables and the BTS camera system were assessed using interclass correlations coefficients. Peak sagittal plane kinematics measured using the Microsoft Kinect(r) camera system explained a significant amount of variance [Range(hip) = 43.5-62.8%; Range(knee) = 67.5-89.6%] in peak kinematics measured using the BTS camera system. Across tasks, peak knee flexion angle and peak hip flexion were found to be consistent and in agreement when the Microsoft Kinect(r) camera system was directly compared to the BTS camera system but these values were improved following application of a corrective factor. The Microsoft Kinect(r) may not be an appropriate surrogate for traditional motion analysis technology, but it may have potential applications as a real-time feedback tool in pathological or high injury risk populations. PMID- 26835549 TI - Structural Properties and Charge Distribution of the Sodium Uranium, Neptunium, and Plutonium Ternary Oxides: A Combined X-ray Diffraction and XANES Study. AB - The charge distributions in alpha-Na2UO4, Na3NpO4, alpha-Na2NpO4, Na4NpO5, Na5NpO6, Na2PuO3, Na4PuO5, and Na5PuO6 are investigated in this work using X-ray absorption near-edge structure (XANES) spectroscopy at the U-L3, Np-L3, and Pu-L3 edges. In addition, a Rietveld refinement of monoclinic Na2PuO3, in space group C2/c, is reported for the first time, and the existence of the isostructural Na2NpO3 phase is revealed. In contrast to measurements in solution, the number of published XANES data for neptunium and plutonium solid phases with a valence state higher than IV is very limited. The present results cover a wide range of oxidation states, namely, IV to VII, and can serve as reference for future investigations. The sodium actinide series show a variety of local coordination geometries, and correlations between the shape of the XANES spectra and the local structural environments are discussed herein. PMID- 26835548 TI - Quercetin-modulated erythrocyte membrane sodium-hydrogen exchanger during human aging: correlation with ATPase's. AB - CONTENT: Quercetin uptake by erythrocytes is rapid. The sodium-hydrogen exchanger (NHE) is a secondary active transporter, regulating intracellular pH, Na(+) concentration and cell volume. OBJECTIVE: The aim of present study was to investigate NHE as a function of human age and effect of quercetin on its activity. The NHE activity was correlated with erythrocytes ATPases. MATERIALS AND METHODS: We analyzed normal, healthy subjects of both sexes (20-82 years). NHE activity was estimated in terms of amiloride-sensitive H+-efflux from acid loaded cells. RESULTS: A significant age-dependent increase in NHE activity was observed during aging in humans. Concentration (10(-3 )M to 10(-8 )M)-dependent in vitro treatment with quercetin causes inhibition of NHE activity. The Na(+)/K(+) -ATPase (r = 0.8882) and Ca(2+)-ATPase (r = 0.9540) activities positively correlated with it. DISCUSSION AND CONCLUSION: The present data show an additional mechanism where dietary flavonoids may exerts beneficial effect during aging. PMID- 26835550 TI - Correction to Tunable Transport Gap in Phosphorene. PMID- 26835551 TI - Copper-Catalyzed Preparation of 2-Aryl-3-cyanobenzofurans with Bright Blue Photoluminescence. AB - Copper-catalyzed cascade synthesis of 2-aryl-3-cyanobenzofurans from o hydroxybenzaldehydes and arylacetonitriles in the presence of copper acetate and sodium methoxide is reported. The synthesized 2-aryl-3-cyanobenzofurans emit bright blue under UV light with a quantum yield up to 88.9%. PMID- 26835552 TI - Peptide Conjugation to a Polymer Coating via Native Chemical Ligation of Azlactones for Cell Culture. AB - Conjugation of biomolecules for stable presentation is an essential step toward reliable chemically defined platforms for cell culture studies. In this work, we describe the formation of a stable and site-specific amide bond via the coupling of a cysteine terminated peptide at low concentration to an azlactone containing copolymer coating. A copolymer of polyethylene glycol methyl ether methacrylate ran-vinyl azlactone-ran-glycidyl methacrylate P(PEGMEMA-r-VDM-r-GMA) was used to form a thin coating (20-30 nm) on silicon and polycarbonate substrates. The formation and stability of coating-peptide bonds for peptides containing free thiols and amines were quantified by X-ray photoelectron spectroscopy (XPS) after exposure to cell culture conditions. Peptides containing a thiol as the only nucleophile coupled via a thioester bond; however, the bond was labile under cell culture conditions and almost all the bound peptides were displaced from the surface over a period of 2 days. Coupling with N-terminal primary amine peptides resulted in the formation of an amide bond with low efficiency (<20%). In contrast, peptides containing an N-terminal cysteine, which contain both nucleophiles (free thiol and amine) in close proximity, bound with 67% efficiency under neutral pH, and were stable under the same conditions for 2 weeks. Control studies confirm that the stable amide formation was a result of an intramolecular rearrangement through a N-acyl intermediate that resembles native chemical ligation. Through a combination of XPS and cell culture studies, we show that the cysteine terminated peptides undergo a native chemical ligation process at low peptide concentration in aqueous media, short reaction time, and at room temperature resulting in the stable presentation of peptides beyond 2 weeks for cell culture studies. PMID- 26835553 TI - Numerical Modeling of Arsenic Mobility during Reductive Iron-Mineral Transformations. AB - Millions of individuals worldwide are chronically exposed to hazardous concentrations of arsenic from contaminated drinking water. Despite massive efforts toward understanding the extent and underlying geochemical processes of the problem, numerical modeling and reliable predictions of future arsenic behavior remain a significant challenge. One of the key knowledge gaps concerns a refined understanding of the mechanisms that underlie arsenic mobilization, particularly under the onset of anaerobic conditions, and the quantification of the factors that affect this process. In this study, we focus on the development and testing of appropriate conceptual and numerical model approaches to represent and quantify the reductive dissolution of iron oxides, the concomitant release of sorbed arsenic, and the role of iron-mineral transformations. The initial model development in this study was guided by data and hypothesized processes from a previously reported,1 well-controlled column experiment in which arsenic desorption from ferrihydrite coated sands by variable loads of organic carbon was investigated. Using the measured data as constraints, we provide a quantitative interpretation of the processes controlling arsenic mobility during the microbial reductive transformation of iron oxides. Our analysis suggests that the observed arsenic behavior is primarily controlled by a combination of reductive dissolution of ferrihydrite, arsenic incorporation into or co-precipitation with freshly transformed iron minerals, and partial arsenic redox transformations. PMID- 26835554 TI - Effect of Advanced HIV Infection on the Respiratory Microbiome. AB - RATIONALE: Previous work found the lung microbiome in healthy subjects infected with HIV was similar to that in uninfected subjects. We hypothesized the lung microbiome from subjects infected with HIV with more advanced disease would differ from that of an uninfected control population. OBJECTIVES: To measure the lung microbiome in an HIV-infected population with advanced disease. METHODS: 16s RNA gene sequencing was performed on acellular bronchoalveolar lavage (BAL) fluid from 30 subjects infected with HIV with advanced disease (baseline mean CD4 count, 262 cells/mm(3)) before and up to 3 years after starting highly active antiretroviral therapy (HAART) and compared with 22 uninfected control subjects. MEASUREMENTS AND MAIN RESULTS: The lung microbiome in subjects infected with HIV with advanced disease demonstrated decreased alpha diversity (richness and diversity) and greater beta diversity compared with uninfected BAL. Differences improved with HAART, but still persisted up to 3 years after starting therapy. Population dispersion in the group infected with HIV was significantly greater than in the uninfected cohort and declined after treatment. There were differences in the relative abundance of some bacteria between the two groups at baseline and after 1 year of therapy. After 1 year on HAART, HIV BAL contained an increased abundance of Prevotella and Veillonella, bacteria previously associated with lung inflammation. CONCLUSIONS: The lung microbiome in subjects infected with HIV with advanced disease is altered compared with an uninfected population both in diversity and bacterial composition. Differences remain up to 3 years after starting HAART. We speculate an altered lung microbiome in HIV infection may contribute to chronic inflammation and lung complications seen in the HAART era. PMID- 26835555 TI - The molecular mechanism and effect of cannabinoid-2 receptor agonist on the blood spinal cord barrier permeability induced by ischemia-reperfusion injury. AB - Previous studies have shown that modulation of the receptor-mediated endocannabinoid system during ischemia injury can induce potent neuroprotective effects. However, little is known about whether cannabinoid-2 (CB2) receptor agonist would produce a protective effect on blood-spinal cord barrier (BSCB) during ischemia. Using an in vivo transient spinal cord ischemia model in rats, JWH-015 (1mg/kg, i.p.), a CB2 receptor selective agonist, or vehicles were injected 20 min before ischemia. The effects of JWH-015 on BSCB permeability, the major structural protein for the formation of caveolae, caveolin-1 (cav-1), tight junction (TJ) protein Occludin and zona occludens protein-1 (ZO-1) were examined at day 1, day 3 and day 7 of reperfusion after transient spinal cord ischemia in rats. Here we demonstrated that JWH-015 significantly down-regulated the expression of cav-1, up-regulated the expression of TJ proteins, and then decreased the permeability of BSCB compared with control group. In addition, using an in vitro BBB model, oxygen glucose deprivation (OGD) was applied to simulate spinal cord ischemia in vitro in Human brain microvascular endothelial cells (HBMECs). JWH-015 greatly increased the transepithelial electrical resistance (TEER) and changed the distribution of ZO-1 and Occludin. Moreover, JWH-015 induced the expression of p-PKB and p-FoxO1 protein and decreased the expression of cav-1, which were greatly reversed by ROS inhibitor or PI3K inhibitor. Taken together, all of these results suggested that JWH-015 might regulate the BSCB permeability and this effect could be related to paracellular and transcellular pathway. And pharmacological CB2R ligands offer a new strategy for BSCB protection during ischemic injury. PMID- 26835556 TI - A temporal predictive code for voice motor control: Evidence from ERP and behavioral responses to pitch-shifted auditory feedback. AB - The predictive coding model suggests that voice motor control is regulated by a process in which the mismatch (error) between feedforward predictions and sensory feedback is detected and used to correct vocal motor behavior. In this study, we investigated how predictions about timing of pitch perturbations in voice auditory feedback would modulate ERP and behavioral responses during vocal production. We designed six counterbalanced blocks in which a +100 cents pitch shift stimulus perturbed voice auditory feedback during vowel sound vocalizations. In three blocks, there was a fixed delay (500, 750 or 1000 ms) between voice and pitch-shift stimulus onset (predictable), whereas in the other three blocks, stimulus onset delay was randomized between 500, 750 and 1000 ms (unpredictable). We found that subjects produced compensatory (opposing) vocal responses that started at 80 ms after the onset of the unpredictable stimuli. However, for predictable stimuli, subjects initiated vocal responses at 20 ms before and followed the direction of pitch shifts in voice feedback. Analysis of ERPs showed that the amplitudes of the N1 and P2 components were significantly reduced in response to predictable compared with unpredictable stimuli. These findings indicate that predictions about temporal features of sensory feedback can modulate vocal motor behavior. In the context of the predictive coding model, temporally-predictable stimuli are learned and reinforced by the internal feedforward system, and as indexed by the ERP suppression, the sensory feedback contribution is reduced for their processing. These findings provide new insights into the neural mechanisms of vocal production and motor control. PMID- 26835557 TI - Large-scale network-level processes during entrainment. AB - Visual rhythmic stimulation evokes a robust power increase exactly at the stimulation frequency, the so-called steady-state response (SSR). Localization of visual SSRs normally shows a very focal modulation of power in visual cortex and led to the treatment and interpretation of SSRs as a local phenomenon. Given the brain network dynamics, we hypothesized that SSRs have additional large-scale effects on the brain functional network that can be revealed by means of graph theory. We used rhythmic visual stimulation at a range of frequencies (4-30 Hz), recorded MEG and investigated source level connectivity across the whole brain. Using graph theoretical measures we observed a frequency-unspecific reduction of global density in the alpha band "disconnecting" visual cortex from the rest of the network. Also, a frequency-specific increase of connectivity between occipital cortex and precuneus was found at the stimulation frequency that exhibited the highest resonance (30 Hz). In conclusion, we showed that SSRs dynamically re-organized the brain functional network. These large-scale effects should be taken into account not only when attempting to explain the nature of SSRs, but also when used in various experimental designs. PMID- 26835558 TI - Predominant role of spinal P2Y1 receptors in the development of neuropathic pain in rats. AB - The role of P2X2/3, P2X3, P2X4 or P2X7 and P2Y2, P2Y6, and P2Y12 receptors in neuropathic pain has been widely studied. In contrast, the role of P2Y1 receptors is scarcely studied. In this study we assessed the role of P2Y1 receptors in several neuropathic pain models in the rat. Furthermore, we analyzed the expression of P2Y1 receptors in the ipsilateral dorsal root ganglia (DRG) and dorsal part of the spinal cord during the development and maintenance of neuropathic pain. We also determined the effect of the P2Y1 receptor antagonist on the expression of P2Y1 receptors. Chronic constriction injury (CCI), spared nerve injury (SNI) or spinal nerve ligation (SNL) produced tactile allodynia from 1 to 14 days after nerve injury. CCI, SNI and SNL enhanced expression of P2Y1 receptors in DRG but not in the dorsal part of the spinal cord at 1-3 days after injury. Intrathecal injection of the selective P2Y1 receptor antagonist MRS2500, but not vehicle, reduced tactile allodynia in rats 1-3 days after CCI, SNI, or SNL. Moreover, intrathecal injection of MRS2500 (at day 1 or 3) reduced neuropathy-induced up-regulation of P2Y1 receptors expression. Intrathecal injection of MRS2500 lost most of the antiallodynic effect when injected 14 days after injury. At this time, MRS2500 did not modify nerve-injury-induced P2Y1 receptors up-regulation. Our results suggest that P2Y1 receptors are localized in DRG, are up-regulated by nerve injury and play a pronociceptive role in development and, to a lesser extent, maintenance of neuropathic pain. PMID- 26835559 TI - Light and electron microscopic analysis of enkephalin-like immunoreactivity in the basolateral amygdala, including evidence for convergence of enkephalin containing axon terminals and norepinephrine transporter-containing axon terminals onto common targets. AB - Modulatory interactions of opioids and norepinephrine (NE) in the anterior subdivision of the basolateral nucleus of the amygdala (BLa) are critical for the consolidation of memories of emotionally arousing experiences. Although there have been several studies of the noradrenergic system in the amygdalar basolateral nuclear complex (BLC), little is known about the chemical neuroanatomy of opioid systems in this region. To address this knowledge gap the present study first examined the distribution of met-enkephalin-like immunoreactivity (ENK-ir) in the BLC at the light microscopic level, and then utilized dual-labeling immunocytochemistry combined with electron microscopy to investigate the extent of convergence of NE and ENK terminals onto common structures in the BLa. Antibodies to ENK and the norepinephrine transporter (NET) were used in these studies. Light microscopic examination revealed that a subpopulation of small nonpyramidal neurons expressed ENK-ir in all nuclei of the BLC. In addition, the somata of some pyramidal cells exhibited light to moderate ENK-ir. ENK+ axon terminals were also observed. Ultrastructural analysis confined to the BLa revealed that most ENK+ axon terminals formed asymmetrical synapses that mainly contacted spines and shafts of thin dendrites. ENK+ terminals forming symmetrical synapses mainly contacted dendritic shafts. Approximately 20% of NET+ terminals contacted a structure that was also contacted by an ENK+ terminal and 6% of NET+ terminals contacted an ENK+ terminal. These findings suggest that ENK and NE terminals in the BLa may interact by targeting common dendrites and by direct interactions between the two types of terminals. PMID- 26835560 TI - Resource allocation models of auditory working memory. AB - Auditory working memory (WM) is the cognitive faculty that allows us to actively hold and manipulate sounds in mind over short periods of time. We develop here a particular perspective on WM for non-verbal, auditory objects as well as for time based on the consideration of possible parallels to visual WM. In vision, there has been a vigorous debate on whether WM capacity is limited to a fixed number of items or whether it represents a limited resource that can be allocated flexibly across items. Resource allocation models predict that the precision with which an item is represented decreases as a function of total number of items maintained in WM because a limited resource is shared among stored objects. We consider here auditory work on sequentially presented objects of different pitch as well as time intervals from the perspective of dynamic resource allocation. We consider whether the working memory resource might be determined by perceptual features such as pitch or timbre, or bound objects comprising multiple features, and we speculate on brain substrates for these behavioural models. This article is part of a Special Issue entitled SI: Auditory working memory. PMID- 26835561 TI - Effect of estrogen on vagal afferent projections to the brainstem in the female. AB - The effects of 17beta-estradiol (E) on the distribution and density of brainstem projections of small or large diameter primary vagal afferents were investigated in Wistar rats using transganglionic transport of wheat germ agglutinin- (WGA; preferentially transported by non-myelinated afferent C-fibers; 2%), or cholera toxin B-subunit- (CTB, 5%; preferentially transported by large myelinated afferent A-fibers) conjugated horseradish peroxidase (HRP) in combination with the tetramethylbenzidine method in age matched ovariectomized (OVX) only or OVX and treated with E (OVX+E; 30 pg/ml plasma) females for 12 weeks. Additionally, these projections were compared to aged matched males. Unilateral microinjection of WGA-HRP into the nodose ganglion resulted in dense anterograde labeling bilaterally, with an ipsilateral predominance in several subnuclei of the nucleus of the solitary tract (NTS) and in area postrema that was greatest in OVX+E animals compared to OVX only and males. Moderately dense anterograde labeling was also observed in paratrigeminal nucleus (PAT) of the OVX+E animals. CTB-HRP produced less dense anterograde labeling in the NTS complex, but had a wider distribution within the brainstem including the area postrema, dorsal motor nucleus of the vagus, PAT, the nucleus ambiguus complex and ventrolateral medulla in all groups. The distribution of CTB-HRP anterograde labeling was densest in OVX+E, less dense in OVX only females and least dense in male rats. Little, if any, labeling was found within PAT in males using either WGA-or CTB-HRP. Taken together, these data suggest that small, non-myelinated (WGA-labeled) and large myelinated (CTB-labeled) diameter vagal afferents projecting to brainstem autonomic areas are differentially affected by circulating levels of estrogen. These effects of estrogen on connectivity may contribute to the sex differences observed in central autonomic mechanisms between gender, and in females with and without estrogen. PMID- 26835562 TI - Pilot Evaluation of Auricular Acupressure in End-Stage Lung Cancer Patients. AB - BACKGROUND: Dyspnea is a common symptom in end-stage lung cancer patients and is only infrequently controlled. Currently, the use of complimentary therapies using traditional Chinese medicine (TCM), including auricular application of Vaccaria segetalis (a small seed), is understudied. Acupressure using auricular Vaccaria segetalis application has been reported as effective in reducing dyspnea when applied to a specific area of the ear associated with lung function in the TCM paradigm. OBJECTIVE: The purpose of this feasibility study was to evaluate the effects of standardized auricular acupressure therapy using Vaccaria segetalis on dyspnea intensity and distress and oxygen saturation in end-stage lung cancer patients. METHODS: The experimental design was three conditions with eight measurement points in time. Patients were randomly assigned to one of three treatment conditions: (1) Standard Care (SC); (2) SC with Vaccaria segetalis taped to random auricular locations (placebo); and (3) SC with Vaccaria segetalis taped to the auricular location deemed specific to lung function in TCM. Subjects were 11 hospice patients with advanced lung cancer and dyspnea. Dyspnea intensity and distress were measured by the Cancer Dyspnea Scale (CDS) and oxygen saturation was measured by pulse oximeter at eight time points. RESULTS: Non parametric statistical analyses suggest the presence of acupressure effects with medium to large effects and significant effect for dyspnea effort. CONCLUSIONS: This pilot information suggests the need for further study of auricular acupressure using Vaccaria segetalis in the dyspneic advanced lung cancer population. PMID- 26835563 TI - Inversion of the stereochemical configuration (3S, 5S)-clavaminic acid into (3R, 5R)-clavulanic acid: A computationally-assisted approach based on experimental evidence. AB - Clavulanic acid (CA), a potent inhibitor of beta-lactamase enzymes, is produced by Streptomyces clavuligerus (Sc) cultivation processes, for which low yields are commonly obtained. Improved knowledge of the clavam biosynthetic pathway, especially the steps involved in the inversion of 3S-5S into 3R-5R stereochemical configuration, would help to eventually identify bottlenecks in the pathway. In this work, we studied the role of acetate in CA biosynthesis by a combined continuous culture and computational simulation approach. From this we derived a new model for the synthesis of N-acetyl-glycyl-clavaminic acid (NAG-clavam) by Sc. Acetylated compounds, such as NAG-clavam and N-acetyl-clavaminic acid, have been reported in the clavam pathway. Although the acetyl group is present in the beta-lactam intermediate NAG-clavam, it is unknown how this group is incorporated. Hence, under the consideration of the experimentally proven accumulation of acetate during CA biosynthesis, and the fact that an acetyl group is present in the NAG-clavam structure, a computational evaluation of the tentative formation of NAG-clavam was performed for the purpose of providing further understanding. The proposed reaction mechanism consists of two steps: first, acetate reacts with ATP to produce a reactive acylphosphate intermediate; second, a direct nucleophilic attack of the terminal amino group of N-glycyl clavaminic on the carbonyl carbon of the acylphosphate intermediate leads to a tetrahydral intermediate, which collapses and produces ADP and N-acetyl-glycyl clavaminic acid. The calculations suggest that for the proposed reaction mechanism, the reaction proceeds until completion of the first step, without the direct action of an enzyme, where acetate and ATP are involved. For this step, the computed activation energy was ?2.82kcal/mol while the reaction energy was ?2.38kcal/mol. As this is an endothermic chemical process with a relatively small activation energy, the reaction rate should be considerably high. The calculations offered in this work should not be considered as a definite characterization of the potential energy surface for the reaction between acetate and ATP, but rather as a first approximation that provides valuable insight about the reaction mechanism. Finally, a complete route for the inversion of the stereochemical configuration from (3S, 5S)-clavaminic acid into (3R, 5R) clavulanic acid is proposed, including a novel alternative for the double epimerization using proline racemase and NAG-clavam formation. PMID- 26835564 TI - Assessing Structural Quality Elements of Pediatric Emergency Care. AB - BACKGROUND AND OBJECTIVE: Emergency departments must have appropriate resources and equipment available to meet the unique needs of children. We assessed the availability of stakeholder-endorsed quality structure performance measures for pediatric emergency department patients. METHODS: A survey of Child Health Corporation of America member hospitals was conducted. Six broad equipment groups were queried: general, monitoring, respiratory, vascular access, fracture management, and specialized pediatric trays. Equipment availability was determined at the level of the individual item, 6 broad groups, and 44 equipment subgroups. The survey queried the availability of 8 protocol/procedure elements: method to identify age-based abnormal vital signs, patient-centered care advisory council, bronchiolitis evidence-based guideline, pediatric radiation dosing standards, suspected child abuse protocols, use of validated pediatric triage tool, and presence of nurse and physician pediatric coordinators. RESULTS: Fifty two percent (22/42) of sites completed the survey. Forty-one percent reported availability of all 113 recommended equipment items. Every hospital reported complete availability of equipment in 77% of the subgroups. The most common missing items were adult-sized lumbar puncture needles, hypothermia thermometers, and various sizes of laryngeal mask airways. Regarding the protocol/procedure elements, a method to identify age-based abnormal vital signs, pediatric radiation dosing standard, and nurse and physician pediatric coordinators were present in 100%. Ninety-five percent used a validated triage tool and had suspected child abuse protocols. CONCLUSIONS: Presence of necessary pediatric emergency equipment is better in the surveyed hospitals than in prior reports. Most responding hospitals have important protocol/procedures in place. These data may provide benchmarks for optimal care. PMID- 26835565 TI - Pediatric Care Provided at Urgent Care Centers in the United States: Compliance With Recommendations for Emergency Preparedness. AB - OBJECTIVES: To describe the compliance of urgent care centers in the United States with pediatric care recommendations for emergency preparedness as set forth by the American Academy of Pediatrics. METHODS: An electronic questionnaire was distributed to urgent care center administrators as identified by the American Academy of Urgent Care Medicine directory. RESULTS: A total of 122 questionnaires of the 872 distributed were available for analysis (14% usable response rate). The most common diagnoses reported for pediatric patients included otitis media (72%), upper respiratory illness (69%), strep pharyngitis (61%), bronchiolitis (30%), and extremity sprain/strain (28%). Seventy-one percent of centers have contacted community emergency medical services (EMS) to transport a critically ill or injured child to their local emergency department in the past year. Sixty-two percent of centers reported having an established written protocol with community EMS and 54% with their local emergency department or hospital. Centers reported the availability of the following essential medications and equipment: oxygen source (75%), nebulized/inhaled beta-agonist (95%), intravenous epinephrine (88%), oxygen masks/nasal cannula (89%), bag-valve mask resuscitator (81%), suctioning device (60%), and automated external defibrillator (80%). Centers reported the presence of the following written emergency plans: respiratory distress (40%), seizures (67%), dehydration/shock (69%), head injury (59%), neck injury (67%), significant fracture (69%), and blunt chest or abdominal injury (81%). Forty-seven percent of centers conduct formal reviews of emergent or difficult cases in a quality improvement format. CONCLUSIONS: Areas for improvement in urgent care center preparedness were identified, such as increasing the availability of essential medications and equipment, establishing transfer and transport agreements with local hospitals and community EMS, and ensuring a structured quality improvement program. PMID- 26835566 TI - Methicillin-Resistant Staphylococcus aureus Subhepatic Abscess Presenting as Pylorospasm in a Neonate. AB - Pylorospasm can present with sonographic findings similar to hypertrophic pyloric stenosis. We present a rare case of methicillin-resistant Staphylococcus aureus subhepatic abscess causing pylorospasm in a neonate. PMID- 26835568 TI - Precordial Catch Syndrome in Elite Swimmers With Asthma. AB - Precordial catch syndrome is a benign cause of chest pain in children and adolescents that remains underrecognized. Because of distinctive symptoms, precordial catch syndrome is not necessarily a diagnosis of exclusion. However, a detailed history eliciting diagnostic features is important, along with a physical examination excluding other pathologic disorders. We present the cases of 2 elite swimmers with asthma who had acute episodes of precordial catch syndrome, one associated with an acute asthma exacerbation and one not, while swimming during competitive swim meets that required rescue efforts for both and eventual evaluation in the emergency department. PMID- 26835567 TI - Managing Children With Autism Spectrum Disorders in Emergency Departments. AB - Taking care of children with autism spectrum disorders is not uncommon in emergency departments as they visit hospital for acute medical and psychiatric conditions. The current prevalence and increasing incidence of autism spectrum disorders will increase the demand for hospital and outpatient services for these children, necessitating education of health care professionals and system adaptations. This paper describes a patient with autism spectrum disorder who had some challenging behavior in the emergency department when he presented with anaphylaxis and discusses management strategies that would help in caring for children with autism spectrum disorders. PMID- 26835569 TI - Emergency Department Presentations of Anti-N-Methyl-D-Aspartate Receptor Encephalitis. AB - Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an acute autoimmune neurological disorder that presents with acute to subacute psychiatric and/or neurological complaints including new onset behavioral changes that may evolve to psychosis and catatonia, cognitive decline, new onset seizures, progressive encephalopathy, and/or movement disorders. Female teens and adults often have an associated ovarian teratoma as an underlying etiology, but most pediatric patients do not have an identifiable associated neoplasm. The diagnosis requires confirmatory serum and/or cerebrospinal fluid analysis findings of anti NMDAR antibody titers. It can be misdiagnosed as a psychiatric condition or a viral encephalitis. The clinical features that distinguish anti-NMDAR encephalitis from a primary psychiatric disorder are the acute onset of the mood and behavioral changes with no history, the waxing and waning of consciousness (delirium/encephalopathy), and primary neurological features such as seizures and abnormal involuntary movements, including dyskinesias and dystonias. The prognosis is improved with earlier recognition and prompt immunotherapy treatment, making this an important diagnosis for emergency physicians. PMID- 26835571 TI - A Novice User of Pediatric Emergency Point-of-Care Ultrasonography Avoids Misdiagnosis in a Case of Chronic Abdominal Distention. AB - A 13-year-old adolescent girl with chronic abdominal distention was referred to the pediatric emergency department after the outpatient workup suggested moderate ascites. Point-of-care ultrasonography performed by the emergency physicians ruled out ascites, instead demonstrating a well-circumscribed cystic mass subsequently identified as an ovarian mucinous cystadenoma. PMID- 26835572 TI - Pediatric Emergency Medicine: Legal Briefs. PMID- 26835573 TI - Telemedicine Applications for the Pediatric Emergency Medicine: A Review of the Current Literature. AB - OBJECTIVE: The aim of this study was to review current literature relating to telemedicine in pediatric emergency medicine including its clinical applications and challenges associated with its implementation. METHODS: We reviewed the literature using standard search methods in accordance with preferred reporting items for systematic reviews and meta-analysis. We included the studies done in emergency settings for all age groups and narrowed our search to the articles that are relevant to "impact on quality of care" and "patient outcome." We also described current telemedicine uses, software, hardware, and other requirements needed for pediatric emergency applications. RESULTS: Telemedicine has a potential role in pediatric emergency medicine for real-time decision making to improve quality of care for children. Logistic and legal challenges exist for pediatric emergency medicine applications similar to its uses in other settings. CONCLUSIONS: Current frameworks exist in the use of telemedicine for pediatric emergency medicine. Research is still needed to see whether clinical outcomes are improved with pediatric emergency telemedicine solutions. Practical issues regarding training, accessibility, and resource allocation should be explored as pediatric emergency telemedicine evolves. PMID- 26835574 TI - Rapid Intravenous Rehydration Therapy in Children With Acute Gastroenteritis: A Systematic Review. AB - BACKGROUND: Rapid intravenous (IV) rehydration is commonly used for the management of pediatric gastroenteritis in the emergency department. The current practice shows wide variation in the volume and rate of rapid IV hydration. The aim of this review was to assess the efficacy of rapid IV rehydration compared with standard method in children with gastroenteritis. METHOD: MEDLINE (1946 2014), EMBASE (1974-2014), and CENTRAL via the Cochrane Library (Issue 8, 2014) were systematically searched to identify eligible studies. Inclusion criteria were randomized controlled trials of rapid IV rehydration in children with gastroenteritis. RESULTS: A total of 1513 articles were retrieved, and our inclusion criteria were met by 3 studies, with a total of 464 participants. The percentage of children who were successfully rehydrated and tolerated oral fluids at 2 to 4 hours after starting IV fluid therapy ranged from 69% to 100% in both rapid IV rehydration and standard method. Time to discharge ranged from 2 to 6 hours (rapid rehydration) versus 2 to 5 hours (standard rehydration). Emergency department revisits ranged from 3% to 16% (rapid rehydration) versus 5% to 14% (standard). Summarized results suggested that rapid IV rehydration may be associated with longer time-to-discharge and higher readmission rates. The new evidence fails to demonstrate superiority of large-volume (60 mL/kg/h) over standard (20 mL/kg/h) IV rehydration. CONCLUSIONS: Standard volume IV rehydration for 1 to 4 hours followed by oral hydration or maintenance IV fluids seems sufficient for most children with gastroenteritis requiring IV fluid administration. However, more evidence is needed to establish an optimal IV rehydration regimen. PMID- 26835575 TI - ECGs in the ED. PMID- 26835576 TI - Child Mental Health Services in the Emergency Department-Disparities in Access. PMID- 26835577 TI - Head Trauma and Intracranial Hemorrhage in Children With Idiopathic Thrombocytopenic Purpura. PMID- 26835578 TI - Maintenance Fluids for Children: Hypotonic Fluids Are Still the Best Choice. PMID- 26835579 TI - Combination of Na-modified zeolite and anion exchange resin for advanced treatment of a high ammonia-nitrogen content municipal effluent. AB - In this study, the exchange equilibrium and kinetic experiments of ammonia nitrogen on the Na-form zeolite were conducted. The results indicated that the presence of humic acid have a negative effect on the equilibrium exchange capacity but have limited influence on the equilibrium time except shorten the sole intra-particle diffusion control time. The exchange equilibrium data could be well fitted by Freundlich model in the absence of humic acid but Langmuir model in the presence of humic acid. While the exchange kinetic data could be well described by pseudo-second-order kinetic model in both situations. An anion exchange resin exhibited high removal efficiency to humic acid and dissolved organic matter through kinetic results and fluorescence excitation-emission matrix (EEM) spectroscopy results. The use of the anion exchange resin prior to the Na-form zeolite improved the ammonia-nitrogen removal efficiency from 78% to 95% and increased the treatment volume of the Na-form zeolite from 51 BV (bed volume) to 76 BV. Both the resin and the Na-form zeolite could be successfully regenerated by the combination of alkaline and sodium chloride. Complete elution of ammonia-nitrogen was achieved when the mass percentage of sodium chloride and alkaline was 10% and 0.6% respectively. PMID- 26835580 TI - An alkali treating strategy for the colloidization of graphitic carbon nitride and its excellent photocatalytic performance. AB - The colloid of graphitic carbon nitride (g-C3N4) was of great importance for practical application. Herein we introduced an alkali treatment route to efficiently colloidize g-C3N4 under mild conditions by destroying the hydrogen bonds between linearly polymeric melon chains and hydrolyzing partial C-NH-C bonds linked two tri-s-triazine units. The obtained colloidal suspension was extremely stable due to its negative charges on surface, and the particle size of several hundred nanometers and the nanobelt-like morphology were revealed by electron microscopy and dynamic light scattering technologies. The structural, optical and functional group analysis demonstrated that the structure of CN heterocycles was preserved after the alkali treatment, and the produced colloidal g-C3N4 can be re-assembled by an electrostatic interaction. Moreover, contributing to the reduced electron-hole recombination, the photocatalytic performance of restacked carbon nitride colloids had more enhanced photocatalytic performance than bulk g-C3N4. PMID- 26835581 TI - Surface zwitterionicalization of poly(vinylidene fluoride) membranes from the entrapped reactive core-shell silica nanoparticles. AB - We demonstrate the preparation and properties of poly(vinylidene fluoride) (PVDF) filtration membranes modified via surface zwitterionicalization mediated by reactive core-shell silica nanoparticles (SiO2 NPs). The organic/inorganic hybrid SiO2 NPs grafted with poly(methyl meth acrylate)-block-poly(2-dimethylaminoethyl methacrylate) copolymer (PMMA-b-PDMAEMA) shell were prepared by surface-initiated reversible addition fragmentation chain transfer (SI-RAFT) polymerization and then used as a membrane-making additive of PVDF membranes. The PDMAEMA exposed on membrane surface and pore walls were quaternized into zwitterionic poly(sulfobetaine methacrylate) (PSBMA) using 1,3-propane sultone (1,3-PS) as the quaternization agent. The membrane surface chemistry and morphology were analyzed by attenuated total reflectance Fourier transform infrared spectroscopy (ATR FTIR), X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM), respectively. The hydrophilicity, permeability and antifouling ability of the investigated membranes were evaluated in detail. It was found that the PSBMA chains brought highly-hydrophilic and strong fouling resistant characteristics to PVDF membranes due to the powerful hydration of zwitterionic surface. The SiO2 cores and PMMA chains in the hybrid NPs play a role of anchors for the linking of PSBMA chains to membrane surface. Compared to the traditional strategies for membrane hydrophilic modification, the developed method in this work combined the advantages of both blending and surface reaction. PMID- 26835582 TI - Electrocatalytic oxidation of dopamine based on non-covalent functionalization of manganese tetraphenylporphyrin/reduced graphene oxide nanocomposite. AB - In the present work, a reduced graphene oxide (RGO) supported manganese tetraphenylporphyrin (Mn-TPP) nanocomposite was electrochemically synthesized and used for the highly selective and sensitive detection of dopamine (DA). The nuclear magnetic resonance, scanning electron microscopy and elemental analysis were confirmed the successful formation of RGO/Mn-TPP nanocomposite. The prepared RGO/Mn-TPP nanocomposite modified electrode exhibited an enhanced electrochemical response to DA with less oxidation potential and enhanced response current. The electrochemical studies revealed that the oxidation of the DA at the composite electrode is a surface controlled process. The cyclic voltammetry, differential pulse voltammetry and amperometry methods were enable to detect DA. The working linear range of the electrode was observed from 0.3 to 188.8 MUM, limit of detection was 8 nM and the sensitivity was 2.606 MUA MUM(-1) cm(-2). Here, the positively charged DA and negatively charged porphyrin modified RGO can accelerate the electrocatalysis of DA via electrostatic attraction, while the negatively charged ascorbic acid (AA) repulsed by the negatively charged electrode surface which supported for good selectivity. The good recovery results obtained for the determination of DA present in DA injection samples and human pathological sample further revealed the good practicality of RGO/Mn-TPP nanocomposite film modified electrode. PMID- 26835583 TI - Organic-inorganic hybrid ZnS(butylamine) nanosheets and their transformation to porous ZnS. AB - Two-dimensional (2D) nanosheets possess the very essential features of nanomaterials, including quantum-confinement effects and unconventional reactivity, and are of special interest for a variety of promising applications. Here we report a facile chemical transformation strategy to prepare porous ZnS nanosheets via the organic-inorganic hybrid ZnS(butylamine) nanosheet-like precursor prepared from zinc diethyldithiocarbamate. The hybrid ZnS(butylamine) precursor show unique nanosheet-like structure composed by ZnS nanocluster region and non-crystalline region. The ZnS nanoclusters with crystallized state show the same crystal orientation in the nanosheets. A simple calcination process in nitrogen can induce the transformation of ZnS(butylamine) hybrid precursor to porous ZnS nanosheets. Different calcination temperature will cause the formation of porous ZnS nanosheets with different microstructure. In addition, the photoelectrochemical properties of the ZnS-based products including ZnS(butylamine) and porous ZnS nanosheets were investigated. This organic inorganic hybrid precursor strategy to porous sulfides would also be suitable for fabricating other metal chalcogenides. PMID- 26835584 TI - Diffusional motion as a gauge of fluidity and interfacial adhesion. Supported alkylphosphonate monolayers. AB - We report on the use of diffusion measurements to gauge the fluidity and surface binding properties of a molecular monolayer. The monolayer film consists of octadecyl-1-phosphonic acid (ODPA) and controlled amounts of a lyso-phosphatidic acid tagged with the fluorescent probe BODIPY (BLPA). The monolayer films were formed using a Langmuir-Blodgett (LB) trough and deposited onto a glass slide. Monolayer morphology was characterized during film formation using Brewster angle microscopy (BAM). Fluorescence Recovery After Photobleaching (FRAP) microscopy was used to measure translational diffusion of BLPA and Fluorescence Anisotropy Decay Imaging (FADI) was used to measure rotational diffusion of the BLPA chromophore. These results provide information on the motional freedom of the probe and, importantly, on the strength of interaction between the probe and the support. Compositional variations in the monolayer give rise to changes in constituent dynamics that reflect intermolecular interactions. PMID- 26835585 TI - An efficient one-pot synthesis of 1,4-disubstituted 1,2,3-triazoles at room temperature by green synthesized Cu NPs using Otostegia persica leaf extract. AB - In this study, copper nanoparticles (Cu NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of CuCl2 . 2H2O solution with aqueous extract of leaves of Otostegia persica containing flavonoid and other phenolics as a main factor which acts as reducing agent and efficient stabilizer. UV-vis spectra gave surface plasmon resonance (SPR) at 560 nm. The Cu NPs were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD). A possible synthesis mechanism of Cu NPs was presented. In addition, we investigated the catalytic activity of Cu NPs for the one-pot synthesis of 1,4-disubstituted 1,2,3 triazoles under mild reaction conditions with good to excellent yields. The catalyst could be easily recovered by centrifugation and reused at least five recycles with no significant decreases in the yields. PMID- 26835586 TI - Phyto mediated biogenic synthesis of gold nanoparticles using Cerasus serrulata and its utility in detecting hydrazine, microbial activity and DFT studies. AB - Green synthesis of Au-NPs using Cerasus serrulata (C. serrulata) leaves extract has emerged as a nontoxic and ecofriendly option, as compared to currently available chemical and/or physical methods and also Au-NPs act as both reducing and stabilizing agent. The developed Au-NPs were characterized with XRD, UV visible spectroscopy, FTIR, SEM, TEM and chemical constituents of C. serrulata leaves extract after and before reduction of Au-NPs have been identified through GC-MS. TEM images confirmed that biosynthesized Au-NPs were spherical in shape and approximately in the range of 5-25 nm. The electrochemical results showed remarkable electrocatalytic activity of the Au-NPs-modified GC electrode in the detection of environmentally hazardous pollutant like hydrazine. The modified electrode exhibits a wide linear range 5 nM to 272 MUM with low detection limit 0.05 MUM. The fabricated sensor shows good selectivity towards other electroactive species as well. Thus the proposed sensor seems to be a potential candidate for developing a simple, rapid and cost-effective electrochemical sensor. The synthesized Au-NPs exhibited higher antibacterial activity against gram negative (Escherichia coli) than gram positive (Staphylococcus aureus) bacteria. DFT studies revealed that the coumarin (CM) present in the C. serrulata leaves extract demonstrated greater reducing and stabilizing properties compared to the properties of other compounds like butylhydroxytoluene (BHT) and hydrocoumarin (HCM) present in the extract. PMID- 26835587 TI - Expression and immunogenicity of recombinant glycoprotein D of herpes simplex virus 1 in Drosophila S2 cells. AB - Herpes simplex virus type 1 (HSV-1) is responsible for cold sores in the general population, but also contributes to the development of other more serious diseases in some circumstances. The viral glycoprotein D (gD) is essential for virus entry into host cells. In the present study, the Drosophila melanogaster Schneider 2 (S2) expression system (DES) was evaluated for the expression of recombinant gD1. The DNA sequences encoding the full-length gD1 (369aa, FLgD1) and a truncated gD1 form corresponding to the ectodomain (314aa, EgD1) were cloned into S2 expression vector pMT/BiP/V5-HisA to generate pMT-EgD1 and pMT FLgD1, respectively. Two forms of gD1 gene were fitted with a hexahistidine tag to facilitate their purification. Cell populations expressing the highest gD1 levels were selected by using a limiting dilution assay. Western blot, flow cytometry (FACS), and confocal immunofluoresence assay demonstrated that the full length form is restrained in the lipid membranes of the cell and the ectodomain form is secreted into the medium. Recombinant ectodomain gD1 was scaled up and purified from the culture medium using nickel nitrilotriacetic acid affinity chromatography, and a maximum production level of 56.8 mg/L of recombinant gD1 was obtained in a shake-flask culture of S2 cells after induction with 5 uM CdCl2 for 4 days. Mice were then immunized with recombinant purified gD1 and produced high titers of antibody measured by enzyme-linked immunosorbent assay (ELISA; 1:5,120,000) as well as high plaque neutralization titer (1:320). Overall, the data indicated that stable expression in S2 cells is a practical way of synthesizing gD1 for use in structural and functional studies in the further study. PMID- 26835589 TI - Prognostic role of elevated preoperative systemic inflammatory markers in localized soft tissue sarcoma. AB - BACKGROUND: Systemic inflammation has been implicated in cancer development and progression. The aim of the present study was to evaluate whether pre-operative systemic inflammatory markers can predict outcomes in bone and soft tissue sarcomas. METHODS: Relevant literature was mainly identified using Pubmed, EMBASE and CNKI. Patients' clinical characteristics, overall survival (OS), disease/relapse free survival (DFS/RFS) with high-level CRP or neutrophils to lymphocytes ratio (NLR) were extracted. The statistics extracted from Kaplan Meier survival curves with log-rank p value were calculated with methods developed by Parmar, Williamson, and Tierney; multivariate Cox hazard regression analysis data were used directly in STATA 10.0. Pooled hazard ratio (HR) and 95% CI were calculated to evaluate the prognostic role of these systemic inflammatory markers (CRP/NLR). RESULTS: After full text review, 11 articles containing 1809 patients were identified as eligible articles. The meta-analysis for survival outcome showed significant prognostic value of systemic inflammatory markers including CRP and NLR in pre-operative blood. The combined HRs (95% CI) for five year overall survival (OS) and disease/recurrence free survival (DFS/RFS) were 2.54 [2.04, 3.16] and 2.28 [1.72, 3.04]. Specifically, higher NLR was associated with decreased 5-year OS (HR 3.75, 95% CI 1.24 to 11.37) and 3 year RFS/DFS (HR 2.43, 95% CI 0.84 to 7.05). Besides, the pooled HR showed a higher risk of 5-year disease progression (HR 2.55, 95% CI 1.60 to 4.08, I2 = 52%) and lower 5-year OS (HR 2.50, 95% CI 2.00 to 3.12, I2 = 0%) in sarcoma patients with high CRP level. We then grouped the meta-analysis by patient source (Asian and non-Asian), tumor stage (I/II or III/IV) and grade (high or low), respectively. All the subgroup analysis showed significant prognostic role in survival condition. The CRP/NLR levels are also found closely related with patient age, tumor stage and size. CONCLUSION: Higher level of pre-operative CRP and NLR demonstrated a significantly higher risk of recurrence and overall decreased survival rates in sarcomas. PMID- 26835588 TI - DHEA improves the antioxidant capacity of endometrial stromal cells and improves endometrium receptivity via androgen receptor. AB - OBJECTIVE: To investigate the effect of dehydroepiandrosterone (DHEA) on mouse decidual endometrial stromal cells (ESCs) and to explore mechanisms regulating endometrial receptivity. STUDY DESIGN: Mouse ESCs were incubated with increasing concentrations of DHEA during decidualization. Treatment with flutamide (FLU), a specific androgen receptor (AR) antagonist, was also performed. Flow cytometry was used to measure intracellular reactive oxygen species (ROS). Real time-PCR was used to determine mRNA expression of decidual PRL-related protein (dPRP), AR, and HomeoboxA10 (HOXA10). Protein levels of AR and HOXA10 were measured by western blot. RESULTS: DHEA significantly inhibited ESC proliferation at concentrations >=1*10(-6)M. DHEA treatment reduced intracellular ROS in a dose dependent manner. Expression of dPRP was minimally affected by DHEA at concentrations of 1 to 100nM. However, DHEA (100nM) significantly increased the expression of HOXA10 at both the mRNA and protein levels (P<0.01). Importantly, this DHEA-mediated increase in HOXA10 was attenuated by treatment with FLU. Finally, neither DHEA nor FLU influenced expression of AR mRNA or protein. CONCLUSION: Low concentration of DHEA improves the antioxidant capacity of decidual ESCs. DHEA treatment may also improve endometrium receptivity via AR. PMID- 26835590 TI - Podoplanin serum and urine concentration in transitional bladder cancer. AB - BACKGROUND: Podoplanin (PDP) is a mucin - a type of transmembrane protein expressed in numerous tissues during ontogeny and in adult animals, including the brain, heart, kidney, osteoblasts and lymphoid organs. OBJECTIVE: The aim of this study was to determine podoplanin concentration in the blood serum and urine of patients with bladder cancer. Quantifying podoplanin concentration and its correlation with various clinicopathological parameters may be useful for more accurate predictions and identifying high-risk patients. METHODS: The present study included 82 patients with bladder cancer confirmed by transurethral resection or cystectomy and 27 healthy volunteers. The Surface Plasmon Resonance Imaging biosensor was applied for the detection of podoplanin in the serum and urine samples. RESULTS: Significant differences in serum and urine podoplanin concentration levels were observed between bladder cancer patients. The statistically significant higher values of PDP were detected in serum of patients with invasive, more aggressive, larger, multifocal tumors. CONCLUSIONS: The association between podoplanin concentration and clinicopathological features indicates that it might be useful while making therapeutic decisions. PMID- 26835591 TI - Dietary restraint and self-discrepancy in male university students. AB - Self-discrepancy describes the distance between an ideal and the actual self. Research suggests that self-discrepancy and dietary restraint are related, causing a significant impact on the person's well-being. However, this relationship has been mostly reported in female and mixed populations. In order to further explore dietary behaviors and their relations to self-discrepancy and well-being-related variables in men, a survey was applied to a non-probabilistic sample of 119 male students from five Chilean state universities (mean age=21.8, SD=2.75). The questionnaire included the Revised Restraint Scale (RRS) with the subscales weight fluctuations (WF) and diet concern (DC), the Satisfaction with Life Scale (SWLS), the Satisfaction with Food-Related Life Scale (SWFL), the Nutrition Interest Scale (NIS), and the Self-discrepancy Index (SDI). Questions were asked about socio-demographic characteristics, eating and drinking habits, and approximate weight and height. A cluster analysis applied to the Z-scores of the RRS classified the following typologies: Group 1 (22.7%), men concerned about weight fluctuations; Group 2 (37.0%), men concerned about diet and weight fluctuations; Group 3 (40.3%), unconcerned about diet and weight fluctuations. The typologies differed in their SDI score, restriction on pastry consumption and reported body mass index (BMI). Students with higher DC and WF scores had a higher BMI, and tended to report high self-discrepancy not only on a physical level, but also on social, emotional, economic and personal levels. This study contributes to the literature on subjective well-being, dietary restraint and self-discrepancy in men from non-clinical samples. PMID- 26835592 TI - Fused Mycobacterium tuberculosis multi-stage immunogens with an Fc-delivery system as a promising approach for the development of a tuberculosis vaccine. AB - Tuberculosis (TB) remains a major health problem worldwide. Currently, the Bacilli Calmette-Guerin (BCG) is the only available licensed TB vaccine, which has low efficacy in protection against adult pulmonary TB. Therefore, the development of a safe and effective vaccine against TB needs global attention. In the present study, a novel multi-stage subunit vaccine candidate from culture filtrate protein-10 (CFP-10) and heat shock protein X (HspX) of Mycobacterium tuberculosis fused to the Fc domain of mouse IgG2a as a selective delivery system for antigen-presenting cells (APCs) was produced and its immunogenicity assessed. The optimized gene constructs were introduced into pPICZalphaA expression vectors, and the resultant plasmids (pPICZalphaA-CFP-10:Hspx:Fcgamma2a and pPICZalphaA-CFP-10:Hspx:His) were transferred into Pichia pastoris by electroporation. The identification of both purified recombinant fusion proteins was evaluated by SDS-PAGE and immunoblotting. Then the immunogenicity of the recombinant proteins with and without BCG was evaluated in BALB/c mice by assessing the level of IFN-gamma, IL-12, IL-4, IL-17 and TGF-beta cytokines. Both multi-stage vaccines (CFP-10:HspX:Fcgamma2a and CFP-10:HspX:His) induced Th1-type cellular responses by producing high level of IFN-gamma (272 pg/mL, p<0.001) and IL-12 (191 pg/mL, p<0.001). However, the Fc-tagged recombinant protein induced more effective Th1-type cellular responses with a low level of IL-4 (10 pg/mL) compared to the CFP-10:HspX:His group. The production of IFN-gamma to CFP 10:HspX:Fcgamma2a was markedly consistent and showed an increasing trend for IL 12 compared with the BCG or CFP-10:HspX:His primed and boosted groups. Findings revealed that CFP-10:Hspx:Fcgamma2a fusion protein can elicit strong Th1 antigen specific immune responses in favor of protective immunity in mice and could provide new insight for introducing an effective multi-stage subunit vaccine against TB. PMID- 26835593 TI - Microbiota, immunity and the liver. AB - The gut harbors a complex community of over 100 trillion microbial cells known to exist in symbiotic harmony with the host influencing human physiology, metabolism, nutrition and immune function. It is now widely accepted that perturbations of this close partnership results in the pathogenesis of several major diseases with increasing evidence highlighting their role outside of the intestinal tract. The intimate proximity and circulatory loop of the liver and the gut has attracted significant attention regarding the role of the microbiota in the development and progression of liver disease. Here we give an overview of the interaction between the microbiota and the immune system and focus on their convincing role in both the propagation and treatment of liver disease. PMID- 26835594 TI - Task difficulty moderates implicit fear and anger effects on effort-related cardiac response. AB - Based on the implicit-affect-primes-effort (IAPE) model (Gendolla, 2012, 2015), the present experiment tested whether objective task difficulty moderates the previously found impact of fear and anger primes on effort-related cardiac response during an arithmetic task. We expected that fear primes would lead to stronger cardiac pre-ejection period (PEP) reactivity than anger primes in an easy task, but that anger primes would lead to a stronger PEP response than fear primes in a difficult task. Results corroborated these predictions. Moreover, there was no evidence that the affect primes induced conscious feelings that could explain the observed cardiac reactivity, suggesting that the primes had the intended implicit effect on effort mobilization. The findings contribute to the accumulating evidence in support of the IAPE model, showing that objective task difficulty is a moderator of implicit affect's influence on effort-related cardiac response. PMID- 26835596 TI - Analysis of telomere length as predictive marker in psoriasis for comorbidities. PMID- 26835597 TI - The effect of sleep on motor learning in the aging and stroke population - a systematic review. AB - There is extensive evidence for positive effects of sleep on motor learning in young individuals; however, the effects of sleep on motor learning in people with stroke and in healthy older individuals are not well understood. The aim of this systematic review was to quantify the association between sleep and procedural memory performance - a marker for motor learning - in healthy older people and people with stroke. After searches in PubMed, Medline and Embase fourteen studies, including 44 subjects after stroke and 339 healthy older participants were included. Overall, sleep was found to enhance motor performance in people after stroke in comparison to an equivalent time of wakefulness. In addition, although evidence is limited, sleep only enhanced motor performance in people after stroke and not in age-matched healthy older adults. In older adults the effect of a sleep intervention did - in general - not differ from equivalent periods of wakefulness. Tasks with whole hand or whole body movements could show significant changes. The results suggest a delayed retention effect after longer breaks including sleep, hinting towards a changed learning strategy as a result of aging. Current evidence for sleep dependent learning in people after stroke is promising, however sparse. PMID- 26835595 TI - Inter-relation between autonomic and HPA axis activity in children and adolescents. AB - Stress research in youth typically considers either the autonomic nervous system or HPA axis. However, these systems are highly coordinated and physically interconnected. We examined whether the inter-relation between cardio-autonomic and HPA axis measures was better associated with perceived stress than their singular associations. Children and adolescents (N=201) collected saliva samples to measure cortisol (AUCAG, AUCI, maximum), wore an electrocardiogram monitor for 24h to derive heart rate variability (HRV; LF, HF, LF/HF ratio), and completed the Perceived Stress Scale. The interaction between sympathovagal modulation (LF, LF/HF ratio) and cortisol awakening response (AUCAG, AUCI, maximum) explained significantly greater variance in perceived stress than either stress system alone. Higher sympathovagal modulation combined with higher cortisol awakening response was associated with greater perceived stress. Findings suggest that the inter-relation between cardio-autonomic and HPA axis activity may advance our understanding of how stress impacts health. PMID- 26835598 TI - Squamous cell carcinoma in situ in association with HPV 11 in Netherton's syndrome patient: a case report. PMID- 26835599 TI - The content and context of physicians' communication with males about human papillomavirus vaccination. AB - A physician's recommendation for human papillomavirus (HPV) vaccine is a key predictor of vaccine uptake; however, little is known about how physicians communicate about HPV vaccine with male patients. We sought to describe physicians' HPV vaccine communication practices with males who are of vaccine eligible age (9-26 years). We surveyed representative samples of pediatric and family medicine physicians in Florida, and assessed whether physicians present HPV vaccine as optional or routine, and as a vaccine that prevents cancer. We also assessed the type of visit during which physicians discuss HPV vaccine with adolescent males and whether other healthcare providers in the practice discuss HPV vaccine or make the initial recommendation. We received 367 completed surveys (50.7% response rate). Few physicians (29.9%) reported they typically present HPV vaccine as routine to males ages 11-12 years, who constitute the target group for routine vaccination. When discussing HPV vaccination, many physicians reported somewhat or strongly emphasizing cancer prevention (80.0%). Physicians most often discussed HPV vaccine when they saw patients for well-child visits (93.0%) and least often at acute care visits (15.3%). Over half reported that at least one other healthcare professional in their practice discusses (56.1%) or makes the initial recommendation for (54.9%) HPV vaccination. Many physicians in our sample are presenting HPV vaccine as optional rather than routine and are missing opportunities to communicate with males about the vaccine. Our findings identify areas for future interventions to improve physicians' HPV vaccine communication and, ultimately, increase the use of this cancer-preventing vaccine. PMID- 26835601 TI - High Diversity of Hepatozoon spp. in Geckos of the Genus Tarentola. AB - : Hemogregarines are the most-commonly reported hemoparasites in reptiles. In this work we analyzed samples from 572 individuals of 6 species of the wall gecko genus Tarentola from European and African countries adjacent to the Mediterranean Sea as well as from the Macaronesian islands. Screening was done using hemogregarine-specific primers for the 18S rRNA gene. Positive amplifications were sequenced so that the diversity of the hemogregarines from these hosts could be assessed within a phylogenetic framework. The results from the phylogenetic analysis showed that within Tarentola, the detected parasites are comprised of at least 4 distinct main lineages of Hepatozoon spp. In clades A and B, the new sequences clustered closely together with the ones previously known from individuals of the genus Tarentola and other species of geckos but also with those from other vertebrate host groups including skinks, snakes, iguanids, and rodents. Clade C included a sample from Tarentola angustimentalis of the Canary Islands. This sequence is the first molecular characterization of these hemogregarines in this archipelago. Until now, this lineage had only been found in lacertids, skinks, and snakes, so this infection extends the host range for this clade. Lastly, in the newly detected clade D, the retrieved parasite sequences form a group currently identified as exclusive of geckos. Our results show that geckos of Tarentola spp. harbor a great diversity of hemogregarines but also that further sampling and other tools, including a multi-locus approach using faster-evolving genetic markers, and identification of definitive hosts are needed to better understand the biology, diversity, and distribution of these parasites. PMID- 26835602 TI - miRNA-mediated crosstalk between transcripts: The missing "linc"? AB - Recently, transcriptome-wide sequencing data have revealed the pervasiveness of intergenic long noncoding RNA (lncRNA) transcription. Subsets of lncRNAs have been demonstrated to crosstalk with and post-transcriptionally regulate mRNAs in a microRNA (miRNA)-dependent manner. Referred to as long noncoding competitive endogenous RNAs (lnceRNAs), these transcripts can contribute to diverse aspects of organismal and cellular biology, likely by providing a hitherto unrecognized layer of gene expression regulation. Here, we discuss the biological relevance of post-transcriptional regulation by lnceRNAs, provide insights on recent advances in the understanding of lnceRNA regulatory networks, and speculate on molecular factors that facilitate miRNA-dependent crosstalk between lnceRNAs and other transcripts. PMID- 26835600 TI - GWAS of 89,283 individuals identifies genetic variants associated with self reporting of being a morning person. AB - Circadian rhythms are a nearly universal feature of living organisms and affect almost every biological process. Our innate preference for mornings or evenings is determined by the phase of our circadian rhythms. We conduct a genome-wide association analysis of self-reported morningness, followed by analyses of biological pathways and related phenotypes. We identify 15 significantly associated loci, including seven near established circadian genes (rs12736689 near RGS16, P=7.0 * 10(-18); rs9479402 near VIP, P=3.9 * 10(-11); rs55694368 near PER2, P=2.6 * 10(-9); rs35833281 near HCRTR2, P=3.7 * 10(-9); rs11545787 near RASD1, P=1.4 * 10(-8); rs11121022 near PER3, P=2.0 * 10(-8); rs9565309 near FBXL3, P=3.5 * 10(-8). Circadian and phototransduction pathways are enriched in our results. Morningness is associated with insomnia and other sleep phenotypes; and is associated with body mass index and depression but we did not find evidence for a causal relationship in our Mendelian randomization analysis. Our findings reinforce current understanding of circadian biology and will guide future studies. PMID- 26835603 TI - A Randomized Trial Evaluating Various Administration Routes of Natalizumab in Multiple Sclerosis. AB - The study's primary objective was to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of single subcutaneous (SC) or intramuscular (IM) 300-mg doses of natalizumab with IV 300-mg doses of natalizumab in patients with multiple sclerosis (MS). Secondary objectives included investigation of the safety, tolerability, and immunogenicity of repeated SC and IM natalizumab doses. DELIVER was a 32-week, open-label, multicenter study of natalizumab-naive patients with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) randomized to receive 300 mg natalizumab by SC injection, IM injection, or IV infusion. PK and PD were evaluated over 8 weeks after the first natalizumab treatment (Part 1) and over 24 weeks with repeated dosing every 4 weeks, beginning at week 8 (Part 2). Seventy-six patients (24 with RRMS and 52 with SPMS) were enrolled in DELIVER. Following SC or IM administration of natalizumab, peak serum concentrations were approximately 40% of those observed with IV administration and showed no major differences in elimination characteristics. Mean bioavailability relative to IV administration was 57.1% to 71.3% with SC administration and 48.7% with IM administration; mean trough serum concentrations were similar with SC or IV administration and lower with IM administration. Following single or multiple doses of natalizumab, PD response was comparable across administration routes and disease stages. No meaningful differences were observed across administration groups in the incidence or nature of overall adverse events, serious adverse events, administration site reactions, hypersensitivity reactions, or antinatalizumab antibodies. These findings support the comparability of PD measures of natalizumab administered IV, SC, or IM. PMID- 26835604 TI - Different digital paths to the keg? How exposure to peers' alcohol-related social media content influences drinking among male and female first-year college students. AB - Despite speculation that peers' alcohol-related content on social media sites (SMS) may influence the alcohol use behaviors of SMS frequenting college students, this relationship has not been investigated longitudinally. The current prospective study assesses the relationship between exposure to peers' alcohol related SMS content and later-drinking among first-year college students. Among 408 first-year students, total exposure to peers' alcohol-related content on Facebook, Instagram, and Snapchat during the initial 6 weeks of college predicted alcohol consumption 6 months later. The rather robust relationship persisted even after students' and close friends drinking were accounted for, indicating that alcohol references on SMS do not simply reflect alcohol use behaviors that would otherwise be observed in the absence of SMS and be predictive of later alcohol use. Findings also illuminate important gender differences in the degree to which peers' alcohol-related SMS content influenced later drinking behavior as well as psychological mediators of this relationship. Among females, enhancement drinking motives and beliefs about the role of alcohol in the college experience fully mediated the relationship between SMS alcohol exposure and later drinking. Males, however, evidenced a much stronger predictive relationship between SMS alcohol exposure and second semester drinking, with this relationship only partially explained by perceptions of drinking norms, enhancement drinking motives, and beliefs about the role of alcohol in the college experience. Implications of these findings for college drinking prevention efforts and directions for future research are discussed. PMID- 26835605 TI - E-cigarette use and disparities by race, citizenship status and language among adolescents. AB - INTRODUCTION: E-cigarette use among adolescents is on the rise in the U.S. However, limited attention has been given to examining the role of race, citizenship status and language spoken at home in shaping e-cigarette use behavior. METHODS: Data are from the 2014 Adolescent California Health Interview Survey, which interviewed 1052 adolescents ages 12-17. Lifetime e-cigarette use was examined by sociodemographic characteristics. Separate logistic regression models predicted odds of ever-smoking e-cigarettes from race, citizenship status and language spoken at home. Sociodemographic characteristics were then added to these models as control variables and a model with all three predictors and controls was run. Similar models were run with conventional smoking as an outcome. RESULTS: 10.3% of adolescents ever used e-cigarettes. E-cigarette use was higher among ever-smokers of conventional cigarettes, individuals above 200% of the Federal Poverty Level, US citizens and those who spoke English-only at home. Multivariate analyses demonstrated that citizenship status and language spoken at home were associated with lifetime e-cigarette use, after accounting for control variables. Only citizenship status was associated with e-cigarette use, when controls variables race and language spoken at home were all in the same model. CONCLUSIONS: Ever use of e-cigarettes in this study was higher than previously reported national estimates. Action is needed to curb the use of e cigarettes among adolescents. Differences in lifetime e-cigarette use by citizenship status and language spoken at home suggest that less acculturated individuals use e-cigarettes at lower rates. PMID- 26835606 TI - Rapid high mass resolution mass spectrometry using matrix-assisted ionization. AB - Matrix-assisted ionization (MAI) is demonstrated to be a robust and sensitive analytical method capable of analyzing proteins such as cholera toxin B-subunit and pertussis toxin mutant from conditions containing relatively high amounts of inorganic salts, buffers, and preservatives without the need for prior sample clean-up or concentration. By circumventing some of the sample preparation steps, MAI simplifies and accelerates the analytical workflow for biological samples in complex media. The benefits of multiply charged ions characteristic of electrospray ionization (ESI) and the robustness of matrix-assisted laser desorption/ionization (MALDI) can be obtained from a single method, making it well suited for analysis of proteins and other biomolecules at ultra-high resolution as demonstrated on an Orbitrap Fusion where protein subunits were resolved for which MALDI-time-of-flight failed. MAI results are compared with those obtained with ESI, MALDI, and laserspray ionization methods and fundamental commonalities discussed. PMID- 26835607 TI - Impact of hyponatremia on nerve conduction and muscle strength. AB - BACKGROUND: Hyponatremia is associated with unstable gait and propensity to falls. The potential contribution of peripheral nervous system dysfunction induced by hyponatremia has not yet been addressed by prospective studies. DESIGN: In the first part of this prospective study, we performed two tests evaluating muscle strength (grip test and quadriceps isometric contraction test) together with a timed up and go (TUG) test in 11 patients with chronic mild-to moderate hyponatremia before and after the normalization of natremia. In the second part, we measured nerve conduction velocities and F-wave latencies in nine patients with profound hyponatremia (< 125 mmol/L) before and after the normalization of natremia. RESULTS: No significant change in muscle strength was observed when natremia was corrected from 127.7 +/- 2.5 to 136.1 +/- 1.8 mmol/L, contrary to a significant improvement in TUG from 14.9 +/- 5.1 to 12.5 +/- 4.7 s (P = 0.006). Nerve conduction velocities and F-wave latencies showed significant improvement in most of the studied nerves when natremia was corrected from 121.9 +/- 2.4 to 135.5 +/- 3.4 mmol/L (e.g. mean increase of 14.3% for motor nerve conduction and mean decrease of 21.6% for F-wave latency of left peroneal nerve). CONCLUSION: Whereas chronic mild-to-moderate hyponatremia has no impact on muscle strength, we demonstrate for the first time an impact of profound hyponatremia on nerve conduction studies. Further studies are needed to ascertain the contribution of these latter results on gait disturbances, propensity to falls and attention deficits associated with hyponatremia. PMID- 26835608 TI - Effect of parenchymal uptake of perfluorobutane microbubbles (Sonazoid((r)) ) on radiofrequency ablation of the liver: in vivo experimental study. AB - BACKGROUND & AIMS: To investigate the differences in mechanical effects and ablation zone between radiofrequency (RF) ablation with and without Sonazoid uptake in an in vivo rabbit liver model. METHODS: Our study was approved by the Institutional Animal Care and Use Committee. Twenty-five rabbits were randomly allotted to one of five ablation durations (i.e., 1, 2, 3, 6 and 12 min). For each rabbit, RF ablation was performed twice, before and 10 min after Sonazoid administration (i.e. control group vs. Sonazoid group), using a 1-cm internally cooled electrode (40W) equipped with a parallelly fixed pressure-monitoring device. During ablation, a 'popping' sound was perceived and recorded along with tissue pressure changes and RF ablation parameters. Then, the ablation volume and microscopic changes were compared. RESULTS: Popping sounds were more frequently perceived in the control group (21/25 vs. 1/25, P < 0.001). The time to first pressure peak was shorter in the Sonazoid group (22.3 +/- 1.1 s vs. 46.3 +/- 4.4 s, P < 0.001) with similar pressures (39.8 +/- 4.2 mmHg vs. 35.6 +/- 4.1 mmHg, P = 0.350). Time to first roll-off and mean power output were significantly less in the Sonazoid group (17.6 +/- 1.2 s vs. 71.2 +/- 8.2 s, P < 0.001; 9.4 +/- 0.3 W vs. 12.8 +/- 0.5 W, P < 0.001). Consequently, the Sonazoid group had lower total energy and ablation volumes for all durations. Microscopically, the control group showed larger conflu-ent disruptions, whereas the Sonazoid group showed many smaller disruptions scattered throughout the ablation zones. CONCLUSIONS: Radiofrequency ablation after Sonazoid uptake induces a smaller ablation zone than conventional RF ablation. However, it appears to ablate the liver tissue with less mechanical effects. PMID- 26835609 TI - Gastrointestinal failure in the ICU. AB - PURPOSE OF REVIEW: The current review summarizes different aspects of assessment of gastrointestinal function and provides a practical approach to management of adult patients with gastrointestinal dysfunction in the ICU. RECENT FINDINGS: Different ways to define gastrointestinal failure have been used in the past. Recently, the term 'acute gastrointestinal injury (AGI)' has been proposed to specifically describe gastrointestinal dysfunction as a part of multiple organ dysfunction syndrome. Possible pathophysiological mechanisms and different aspects in assessment of gastrointestinal function in adult ICU patients are presented. Currently, there is no single marker that could reliably describe gastrointestinal dysfunction. Therefore, monitoring and management is still based on complex assessment of different gastrointestinal symptoms and feeding intolerance, even though this approach includes a large amount of subjectivity. The possible role of biomarkers (citrulline, enterohormones, etc.) and additional parameters like intra-abdominal pressure remains to be clarified. SUMMARY: Defining gastrointestinal failure remains challenging but broad consensus needs to be reached and disseminated soon to allow conduct of interventional studies. A systematic approach to management of gastrointestinal problems is recommended. PMID- 26835610 TI - Pattern of lymph node metastasis in hypopharyngeal squamous cell carcinoma and indications for level VI lymph node dissection. AB - BACKGROUND: The purpose of this study was to determine the incidence, risk factors, and prognostic significance of level VI lymph node metastases from hypopharyngeal squamous cell carcinoma (SCC). METHODS: A retrospective review of 68 previously untreated patients with hypopharyngeal SCC who underwent level VI node dissection was performed. RESULTS: Level VI lymph node metastases occurred in 27.9% of patients. The occult metastasis rate of level VI node was 14.3%. Patients with level VI metastasis had significantly lower disease-specific (55.1% vs 26.3%) and overall survival rates (73.5% vs 31.6%). Level VI lymph node metastasis was significantly correlated with regional recurrence (83.7% vs 63.2%) and distant metastasis (67.3% vs 47.4%). Multivariate analysis revealed that pyriform sinus apex invasion (odds ratio [OR] = 5.106) was an independent factor for level VI nodal metastasis. CONCLUSION: Level VI lymph nodes should be removed in patients with pyriform sinus apex invasion, especially in those with advanced nodal disease. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1969-E1973, 2016. PMID- 26835611 TI - Mental health and gender dysphoria: A review of the literature. AB - Studies investigating the prevalence of psychiatric disorders among trans individuals have identified elevated rates of psychopathology. Research has also provided conflicting psychiatric outcomes following gender-confirming medical interventions. This review identifies 38 cross-sectional and longitudinal studies describing prevalence rates of psychiatric disorders and psychiatric outcomes, pre- and post-gender-confirming medical interventions, for people with gender dysphoria. It indicates that, although the levels of psychopathology and psychiatric disorders in trans people attending services at the time of assessment are higher than in the cis population, they do improve following gender-confirming medical intervention, in many cases reaching normative values. The main Axis I psychiatric disorders were found to be depression and anxiety disorder. Other major psychiatric disorders, such as schizophrenia and bipolar disorder, were rare and were no more prevalent than in the general population. There was conflicting evidence regarding gender differences: some studies found higher psychopathology in trans women, while others found no differences between gender groups. Although many studies were methodologically weak, and included people at different stages of transition within the same cohort of patients, overall this review indicates that trans people attending transgender health-care services appear to have a higher risk of psychiatric morbidity (that improves following treatment), and thus confirms the vulnerability of this population. PMID- 26835612 TI - Fertility options in transgender people. AB - Hormonal and surgical treatments for transgender people have a devastating effect on the possibility for these patients to reproduce. Additionally, transgender people tend to start sex reassignment treatment at a young age, when reproductive wishes are not yet clearly defined nor fulfilled. The most recent Standards of Care of the World Professional Association for Transgender Health recommend clearly informing patients regarding their future reproductive options prior to initiation of treatment. This review gives an overview of the current knowledge and state-of-the-art techniques in the field of fertility preservation for transgender people. Where genital reconstructive surgery definitely results in sterility, hormone therapy on the other hand also has an important, but partially reversible impact on fertility. The current fertility preservation options for trans men are embryo cryopreservation, oocyte cryopreservation and ovarian tissue cryopreservation. For trans women, sperm cryopreservation, surgical sperm extraction and testicular tissue cryopreservation are possible. Although certain fertility preservation techniques could be applicable in a standardized manner based on clear biological criteria, the technique that eventually will be performed should be the preferred choice of the patient after extended explanation of all possible options. PMID- 26835613 TI - Evaluation of conversion coefficients relating air-kerma to H*(10) using primary and transmitted x-ray spectra in the diagnostic radiology energy range. AB - According to the International Commission on Radiation Units and Measurements (ICRU), the relationship between effective dose and incident air-kerma is complex and depends on the attenuation of x-rays in the body. Therefore, it is not practical to use this quantity for shielding design purposes. This correlation is adopted in practical situations by using conversion coefficients calculated using validated mathematical models by the ICRU. The ambient dose equivalent, H*(10), is a quantity adopted by the IAEA for monitoring external exposure. Dose constraint levels are established in terms of H*(10), while the radiation levels in radiometric surveys are calculated by means of the measurements of air-kerma with ion chambers. The resulting measurements are converted into ambient dose equivalents by conversion factors. In the present work, an experimental study of the relationship between the air-kerma and the operational quantity ambient dose equivalent was conducted using different experimental scenarios. This study was done by measuring the primary x-ray spectra and x-ray spectra transmitted through materials used in dedicated chest radiographic facilities, using a CdTe detector. The air-kerma to ambient dose equivalent conversion coefficients were calculated from these measured spectra. The resulting values of the quantity ambient dose equivalent using these conversion coefficients are more realistic than those available in the literature, because they consider the real energy distribution of primary and transmitted x-ray beams. The maximum difference between the obtained conversion coefficients and the constant value recommended in national and international radiation protection standards is 53.4%. The conclusion based on these results is that a constant coefficient may not be adequate for deriving the ambient dose equivalent. PMID- 26835614 TI - Effects of aperture averaging and beam width on a partially coherent Gaussian beam over free-space optical links with turbulence and pointing errors. AB - Joint effects of aperture averaging and beam width on the performance of free space optical communication links, under the impairments of atmospheric loss, turbulence, and pointing errors (PEs), are investigated from an information theory perspective. The propagation of a spatially partially coherent Gaussian beam wave through a random turbulent medium is characterized, taking into account the diverging and focusing properties of the optical beam as well as the scintillation and beam wander effects. Results show that a noticeable improvement in the average channel capacity can be achieved with an enlarged receiver aperture in the moderate-to-strong turbulence regime, even without knowledge of the channel state information. In particular, it is observed that the optimum beam width can be reduced to improve the channel capacity, albeit the presence of scintillation and PEs, given that either one or both of these adverse effects are least dominant. We show that, under strong turbulence conditions, the beam width increases linearly with the Rytov variance for a relatively smaller PE loss but changes exponentially with steeper increments for higher PE losses. Our findings conclude that the optimal beam width is dependent on the combined effects of turbulence and PEs, and this parameter should be adjusted according to the varying atmospheric channel conditions. Therefore, we demonstrate that the maximum channel capacity is best achieved through the introduction of a larger receiver aperture and a beam-width optimization technique. PMID- 26835615 TI - Neural network method to correct bidirectional effects in water-leaving radiance. AB - Ocean color algorithms that rely on "atmospherically corrected" nadir water leaving radiances to infer information about marine constituents such as the chlorophyll concentration depend on a reliable method to convert the angle dependent measured radiances from the observation direction to the nadir direction. It is also important to convert the measured radiances to the nadir direction when comparing and merging products from different satellite missions. The standard correction method developed by Morel and coworkers requires knowledge of the chlorophyll concentration. Also, the standard method was developed based on the Case 1 (open ocean) assumption, which makes it unsuitable for Case 2 situations such as turbid coastal waters. We introduce a neural network method to convert the angle-dependent water-leaving radiance (or the corresponding remote sensing reflectance) from the observation direction to the nadir direction. This method relies on neither an "atmospheric correction" nor prior knowledge of the water constituents or the inherent optical properties. It directly converts the remote sensing reflectance from an arbitrary slanted viewing direction to the nadir direction by using a trained neural network. This method is fast and accurate, and it can be easily adapted to different remote sensing instruments. Validation using NuRADS measurements in different types of water shows that this method is suitable for both Case 1 and Case 2 waters. In Case 1 or chlorophyll-dominated waters, our neural network method produces corrections similar to those of the standard method. In Case 2 waters, especially sediment-dominated waters, a significant improvement was obtained compared to the standard method. PMID- 26835616 TI - Performance characteristics of dual-pumped hybrid EDFA/Raman optical amplifier. AB - This paper suggests a hybrid amplifier using an erbium-doped fiber amplifier (EDFA) and Raman amplifier (RA) with dual-pump configuration. This hybrid EDFA/RA optical amplifier (HOA) is dual pumped. The EDFA is forward biased with 980 nm while the RA is reverse biased with 1450 nm in the dual-pump configuration. Both the gain and noise figure are experimentally studied and compared with experimental values of the EDFA/Raman HOA with different pump configurations. The optimum values of the affecting parameters are investigated to get the best characteristics of the HOA, including high gain and a low noise figure. A high gain of 31 dB and low noise of 3.8 dB are achieved. In addition, the flat gain in the wavelength range 1545-1565 nm and the optical signal-to-noise ratio is reduced to 24 dB. PMID- 26835617 TI - Multilayer four-flux matrix model accounting for directional-diffuse light transfers. AB - The four-flux model is a method to solve light radiative-transfer problems in planar, possibly multilayer structures. The light fluxes are modeled as two collimated and two diffuse beams propagating forward and backward perpendicularly to the layer stack. In the present contribution, we develop a four-flux model relying on a matrix formalism to determine the reflectance and transmittance factors of stacks of components by knowing those of each individual component. This model is also extended to generate the bidirectional scattering distribution function of the stack by considering an incoming collimated flux in any direction and by taking into account the directionality of the diffuse fluxes exiting from the material at the border components of the stack. The model is applied to opaque Lambertian backgrounds with flat or rough interfaces for which analytical expressions of the BSDF are obtained. PMID- 26835618 TI - Sub-500 nm hard x ray focusing by compound long kinoform lenses. AB - The focusing performance of polymethyl methacrylate compound long kinoform lenses with 70 MUm aperture and 19.5 mm focal length was characterized with 8 keV x rays using the knife-edge scan method at the 4W1A transmission x-ray microscope beamline of Beijing Synchrotron Radiation Facility. The experiment result shows a best FWHM focus size of 440 nm with 31% diffraction efficiency. PMID- 26835619 TI - Efficient and compact orthogonally polarized dual-wavelength Nd:YVO4 laser at 1342 and 1345 nm. AB - Based on a free-running diode-end-pumped a-cut Nd:YVO4 laser with output power of 3.61 W at a single wavelength of pi-polarized 1342 nm, we further obtain a 1.82 W sigma-polarized 1345 nm laser with a slope efficiency of about 22.3% by introducing an intracavity etalon, for the first time to the best of our knowledge. In addition, a simultaneous dual-wavelength orthogonally polarized laser at pi-polarized 1342 nm and sigma-polarized 1345 nm can also be achieved with a maximum output power of 1.35 W. The dual-wavelength laser provides a potential laser source for terahertz wave generation. PMID- 26835620 TI - Steel-surface defect detection using a switching-lighting scheme. AB - In this paper a novel filtering scheme combined with a lighting method is proposed for defect detection in steel surfaces. A steel surface has non-uniform brightness and various shaped defects, which cause difficulties in defect detection. To solve this problem we propose a sub-optimal filtering that is combined with a switching-lighting method. First, dual-light switching lighting (DLSL) is explained, which decreases the effect of non-uniformity of surface brightness and improves the detection accuracy. By using the DLSL method, defects are represented as alternated black and white patterns regardless of the size, shape, or orientation of defects. Therefore, defects can be detected by finding alternated black and white patterns. Second, we propose a scheme for detecting defects in steel-surface images acquired using the DLSL method. The presence of scales strongly affects the optical properties of the surface. Moreover, the textures of steel-plate images vary greatly because of the temperature and grade of steel. Therefore, conventional filter-design methods are not effective for different image textures. A sub-optimal scheme based on an optimized general finite impulse-response filter is also proposed. Finally, experimental results conducted on steel-surface images from an actual steel-production line show the effectiveness of the proposed algorithm. PMID- 26835621 TI - High-accuracy dithering-based three-dimensional data compression algorithms by phase correction. AB - The Holoimage technique can substantially reduce three-dimensional (3D) shape data sizes by converting the data into regular 24-bit 2D images. A dithering based compression algorithm was recently proposed to further reduce the data size by only utilizing three bits to represent 3D shape data. However, our research finds that the recovery accuracy of the dithering-based algorithm is not very high due to the loss of information in the dithering process. In addition, we find that the final 3D recovery accuracy is highly related to the phase information. In this paper, to address the low accuracy problem, we propose two different phase-correction methods to store the phase-error information and retrieve the absolute phase with higher accuracy. Both methods can provide recovered 3D results with much better quality. Experimental results are presented to verify the performance of the proposed methods. PMID- 26835622 TI - Fiber refractive index sensor based on dual polarized Mach-Zehnder interference caused by a single-mode fiber loop. AB - A novel refractive index (RI) sensor head is proposed and experimentally demonstrated in this paper. The proposed sensor head is composed of a segment of bared single-mode fiber and a fiber holder that is fabricated by a 3D printer. The mechanism of the sensor head is based on dual polarized Mach-Zehnder interference. According to the aforementioned mechanism, we derived that the RI responses of the resonance dips possess an exponential functional manner when the E field is along the fast or slow axes. In addition, based on the finite element method, we found that the resonance dips wavelength responses are more sensitive when the input E field is along the fast axis. A confirmation experiment was performed, and the results confirmed our hypothesis. The maximum arithmetic mean value of RI response is about 657.895 nm/RIU for the proposed sensor head when the ambient RI changes from 1.3350 to 1.4110. Moreover, in the case of the proposed liquid RI sensor head, aligning the E field along the fast axis is the potentially needed condition for polarization. PMID- 26835623 TI - Polarizing grating color filters with large acceptance angle and high transmittance. AB - We design and simulate a polarizing color filter with a sub-wavelength metal dielectric grating. It manifests several advantages: a large acceptance angle (up to +/-50 degrees ), high transmittance (74.3%-92.7%), low absorption loss (~3.3%), and a high extinction ratio. This polarizing color filter can be integrated into a liquid-crystal display (LCD) backlight system to simultaneously recycle the light according to its color and polarization. In combination with a specially designed directional backlight, this newly proposed LCD system can theoretically improve optical efficiency up to ~2.5*, and also provides a large ambient contrast ratio and a wide view. Our approach enables an ultra-low-power LCD without using the complicated field-sequential-color technique. PMID- 26835624 TI - Spectral narrowing and stabilization of interband cascade laser by volume Bragg grating. AB - A volume Bragg grating recorded in photo-thermo-refractive glass was used to spectrally lock the emission from an 18-MUm-wide interband cascade laser ridge to a wavelength of 3.12 MUm. The spectral width of emission into the resonant mode is narrowed by more than 300 times, and the thermal wavelength shift is reduced by 60 times. While the power loss penalty is about 30%, the spectral brightness increases by 200 times. PMID- 26835625 TI - Accuracy of image-plane holographic tomography with filtered backprojection: random and systematic errors. AB - This paper explores the concept of image-plane holographic tomography applied to the measurements of laser-induced thermal gradients in an aqueous solution of a photosensitizer with respect to the reconstruction accuracy of three-dimensional variations of the refractive index. It uses the least-squares estimation algorithm to reconstruct refractive index variations in each holographic projection. Along with the bitelecentric optical system, transferring focused projection to the sensor plane, it facilitates the elimination of diffraction artifacts and noise suppression. This work estimates the influence of typical random and systematic errors in experiments and concludes that random errors such as accidental measurement errors or noise presence can be significantly suppressed by increasing the number of recorded digital holograms. On the contrary, even comparatively small systematic errors such as a displacement of the rotation axis projection in the course of a reconstruction procedure can significantly distort the results. PMID- 26835626 TI - Large elliptical nanostructured gradient-index microlens. AB - We demonstrate the feasibility of the development of a gradient-index elliptical microlens with a size of 75*125 MUm using nanostructured glass technology. The gradient index is obtained by means of a discrete internal structure composed of two glasses with feature sizes much smaller than the wavelength of the incident light. A modified photonic crystal fiber-drawing technique is used for the lens fabrication. The elliptical shape of the lens is obtained by a novel final drawing stage where the spherically symmetric lens preform is drawn into an elliptical form by collapsing two large air holes placed in the preform during assembly. The effective focal lengths of 160 and 260 MUm for the orthogonal axes are obtained experimentally for the fabricated lens, and show good agreement with those predicted by the effective medium theory and the full-wave beam propagation simulations. PMID- 26835627 TI - Finite element modeling of light propagation in turbid media under illumination of a continuous-wave beam. AB - Spatially resolved spectroscopy provides a means for measuring the optical properties of biological tissues, based on analytical solutions to diffusion approximation for semi-infinite media under the normal illumination of an infinitely small light beam. The method is, however, prone to error in measurement because the actual boundary condition and light beam often deviate from that used in deriving the analytical solutions. It is therefore important to quantify the effect of different boundary conditions and light beams on spatially resolved diffuse reflectance in order to improve the measurement accuracy of the technique. This research was aimed at using finite element method (FEM) to model light propagation in turbid media, subjected to normal illumination by a continuous-wave beam of infinitely small or finite size. Three types of boundary conditions [i.e., partial current (PCBC), extrapolated (EBC), and zero (ZBC)] were evaluated and compared against Monte Carlo (MC) simulations, since MC could provide accurate fluence rate and diffuse reflectance. The effect of beam size was also investigated. Overall results showed that FEM provided results as accurate as those of the analytical method when an appropriate boundary condition was applied. ZBC did not give satisfactory results in most cases. FEM-PCBC yielded a better fluence rate at the boundary than did FEM-EBC, while they were almost identical in predicting diffuse reflectance. Results further showed that FEM coupled with EBC effectively simulated spatially resolved diffuse reflectance under the illumination of a finite size beam. A large beam introduced more error, especially within the region of illumination. Research also confirmed an earlier finding that a light beam of less than 1 mm diameter should be used for estimation of optical parameters. FEM is effective for modeling light propagation in biological tissues and can be used for improving the optical property measurement by the spatially resolved technique. PMID- 26835628 TI - Dual wavelength laser-induced damage threshold measurements of alumina/silica and hafnia/silica ultraviolet antireflective coatings. AB - An approach for the measurement of the laser-induced damage threshold with two wavelengths combined was made while testing antireflective coatings for the wavelengths 266 and 532 nm. Samples were made of Al2O3/SiO2 and HfO2/SiO2 ion beam sputtered films. The results show that adding radiation of a second wavelength might lead to a significant reduction of the threshold. The damage morphology of single and dual wavelength tests is very similar and does not suggest an altered damage mechanism. Further investigations indicated that the dual wavelength threshold is a function of the temporal delay of the two pulses. PMID- 26835629 TI - High-speed high-resolution heterodyne interferometer using a laser with low beat frequency. AB - A high-speed high-resolution heterodyne interferometer using a laser with low beat frequency is developed. The interferometer has two spatially separated parallel beams with different frequencies. Two interference signals with opposite Doppler shift are optically generated by the interferometric optics. The measurement electronics uses two identical phasemeters for the two opposite interference signals. The two interference signals are selectively used according to the speed of the target, which makes sure that the Doppler shift of the selected signal is always positive, so that the measurable speed is no longer limited by the beat frequency of the laser source. Experimental results show that the measurement resolution is 0.62 nm. The measurable speed can exceed the restriction determined by the beat frequency. Compared with a commercial interferometer, the displacement difference is less than 40 nm in a travel range of 900 mm. PMID- 26835630 TI - Effective light absorption and its enhancement factor for silicon nanowire-based solar cell. AB - Although nanowire (NW) antireflection coating can enhance light trapping capability, which is generally used in crystal silicon (CS) based solar cells, whether it can improve light absorption in the CS body depends on the NW geometrical shape and their geometrical parameters. In order to conveniently compare with the bare silicon, two enhancement factors E(T) and E(A) are defined and introduced to quantitatively evaluate the efficient light trapping capability of NW antireflective layer and the effective light absorption capability of CS body. Five different shapes (cylindrical, truncated conical, convex conical, conical, and concave conical) of silicon NW arrays arranged in a square are studied, and the theoretical results indicate that excellent light trapping does not mean more light can be absorbed in the CS body. The convex conical NW has the best light trapping, but the concave conical NW has the best effective light absorption. Furthermore, if the cross section of silicon NW is changed into a square, both light trapping and effective light absorption are enhanced, and the Eiffel Tower shaped NW arrays have optimal effective light absorption. PMID- 26835631 TI - Goniospectrometric space curve for coatings with special effect pigments. AB - Advanced application of eye-catching effects occurring in coatings with special effect pigments requires controlling their appearance. For this purpose, angular dependent reflectance must be analyzed in terms of the used flakes and their distribution inside the coating; it is important to know the size of the surface area they cover, and the position and precision of their orientation. These properties were varied using our numerical model, which gave an angular dependent reflectance factor for each set of coating parameters. The method was applied to analyze how well the calculated goniometric reflectance factor could characterize the appearance of effect coatings. For this purpose, the spectra were transformed in the goniospectrometric space, and the obtained curve was analyzed. While its shape, position, and orientation in the space reveal the optical makeup of the coating, the goniospectrometric space curve could serve as an appearance fingerprint of the corresponding sample. The applicability of the theoretical predictions was confirmed using a coating with metallic flakes and one with mica based Fe2O3 coated flakes. PMID- 26835632 TI - Fast particle characterization using digital holography and neural networks. AB - We propose using a neural network approach in conjunction with digital holographic microscopy in order to rapidly determine relevant parameters such as the core and shell diameter of coated, non-absorbing spheres. We do so without requiring a time-consuming reconstruction of the cell image. In contrast to previous approaches, we are able to obtain a continuous value for parameters such as size, as opposed to binning into a discrete number of categories. Also, we are able to separately determine both core and shell diameter. For simulated particle sizes ranging between 7 and 20 MUm, we obtain accuracies of (4.4+/-0.2)% and (0.74+/-0.01)% for the core and shell diameter, respectively. PMID- 26835633 TI - Depth map sensor based on optical doped lens with multi-walled carbon nanotubes of liquid crystal. AB - In this paper, we present a novel design concept for determining the depth map of three-dimensional (3D) scenes based on an electrically controlled liquid crystal (LC) lens. The advantages of the proposed method are that it does not need any mechanical movements and a large amount of computations to acquire a depth map of a 3D scene in a relatively short amount of time. The tunable-focus LC lens doped with multi-walled carbon nanotubes is to become a key optical component for determining a depth map system. Sequenced two-dimensional images of slightly different perspectives are recorded in a short time, and the depth map of the 3D scene, according to a proposed depth estimation method and a focusing evaluation function, can be acquired in a simple way. This new method to acquire a depth map based on a doped LC lens maximizes the use of the proposed LC lens. The proposed system is novel in its compact, simple, and fast features, so we believe the proposed method can open a new creative dimension in image analysis and imaging systems and can also overcome the limitations of the conventional imaging mode. PMID- 26835634 TI - Polarization-independent plasmonic subtractive color filtering in ultrathin Ag nanodisks with high transmission. AB - We demonstrate a TE/TM polarization-independent plasmonic subtractive color filtering scheme employing ultrathin two-dimensional Ag nanodisks. These TE/TM polarization-independent subtractive color filters exhibit small feature sizes (below 200 nm) and high transmission up to 70% in the visible spectral region, superior to previously reported plasmonic color filters. Simulated optical transmission spectra and colors are in good agreement with experimental results. The color-filtering behaviors strongly depend on thickness and period of nanodisks. Underlying mechanisms are also discussed in detail. PMID- 26835635 TI - Range compensation for accurate 3D imaging system. AB - Range determination has crucial dependency of intensity over distance due to the fact that output of a range gated system is the reflectivity and range information expressed in term of intensity. From our experimental study, the analyzed trend line of reflected intensity versus range agrees with the theoretical model where it underlies an inverse range-squared dependency. Considering the energy attenuation factor for a better three-dimensional (3D) solution, a range compensation model is derived based on time slicing technique to compensate the effect imposed by distance beyond an optimum range. A range gated imaging system with pulse profile feedback is proposed in order to apply the range compensation model. Experimental results show noticeable improvement as compared to the conventional weighted average method for reflected laser pulse data across different ranges and 3D surface reconstruction using the proposed range compensation model. PMID- 26835636 TI - Diffractive optical element with same diffraction pattern for multicolor light emitting diodes. AB - The wavelength-division multiplexing technique can be utilized in visible light communication to increase the channel capacity when a multicolor mixed white LED is used as light source. In such an application, the illumination area of LEDs should be invariant to the incident wavelength, so as to decrease interference within the adjacent regions. Diffractive optical elements (DOEs) can be used in the optical transmitter system to shape the diffraction patterns into polygons. However, traditional DOEs illuminated by a multicolor mixed white LED would result into diffraction patterns with unequal sizes. In this paper, a hybrid algorithm which combines particle swarm optimization with a genetic algorithm is proposed for multicolor oriented DOEs design. A DOE is designed and fabricated for blue and red LEDs, and experimental results show that diffraction patterns with rather good uniformity as well as quasi-equal size for red and blue LEDs are obtained. PMID- 26835637 TI - Analysis of dead zone sources in a closed-loop fiber optic gyroscope. AB - Analysis of the dead zone is among the intensive studies in a closed-loop fiber optic gyroscope. In a dead zone, a gyroscope cannot detect any rotation and produces a zero bias. In this study, an analysis of dead zone sources is performed in simulation and experiments. In general, the problem is mainly due to electrical cross coupling and phase modulation drift. Electrical cross coupling is caused by interference between modulation voltage and the photodetector. The cross-coupled signal produces spurious gyro bias and leads to a dead zone if it is larger than the input rate. Phase modulation drift as another dead zone source is due to the electrode contamination, the piezoelectric effect of the LiNbO3 substrate, or to organic fouling. This modulation drift lasts for a short or long period of time like a lead-lag filter response and produces gyro bias error, noise spikes, or dead zone. For a more detailed analysis, the cross-coupling effect and modulation phase drift are modeled as a filter and are simulated in both the open-loop and closed-loop modes. The sources of dead zone are more clearly analyzed in the simulation and experimental results. PMID- 26835638 TI - Compensation for correlated error in multilayer interferometer. AB - Wavelength tuning interferometry is used to measure and estimate the surface shape of a sample. However, in multilayer interferometry (e.g., a lithium niobate [LNB] crystal wafer attached to a supporting plate), the correlated error between the higher harmonics and the phase-shift error causes considerable error in the calculated phase. In this study, the correlated errors calculated by various types of windowed phase-shifting algorithms are analyzed in connection with the characteristic polynomial theory and Fourier representation of the algorithms. The surface shape and optical thickness variation of the LNB wafer are measured simultaneously using the windowed phase-shifting algorithms. The results are compared in terms of the observed ripples and measurement repeatability. The experimental results show that the 4N-3 algorithm is optimal and possesses the smallest repeatability error. PMID- 26835639 TI - Optical gain characterization of Perylene Red-doped PMMA for different pump configurations. AB - The optical gain is measured in Perylene Red (PR)-doped polymethyl methacrylate (PMMA) slabs for copropagating and transverse pumping configurations based on a single-pass pump-probe method where a small signal is used as a probe beam. The gain is characterized in terms of the stimulated gain coefficient (g(S)) for both pump configurations. This material property determines the strength of pump absorption and coupling to the probe signal beam through stimulated emission. For copropagating pumping, g(S) was found to be (3.05+/-0.17)*10(-3) m/W for ~0.05 mM PR-doped PMMA using a 633 nm probe laser, pumping with a 532 nm CW laser. For transverse pumping, g(S) was found to be (3.28+/-0.09)*10(-3) m/W for a ~0.15 mM sample. The small difference in the gain coefficient is attributed to the difference in concentration. The stimulated gain coefficient, a material property of the gain medium independent of the pump configuration and experimental setup, offers a useful and convenient way to characterize the optical gain for solid state lasers or amplifiers. PMID- 26835640 TI - Correction of illumination fluctuations in phase-shifting technique by use of fringe histograms. AB - With phase-shifting technique, the illumination fluctuations may decrease measurement accuracy. This paper presents a simple method for solving this problem by use of fringe histograms. A fringe pattern containing bright and dark fringes is recognized as an image having two classes of pixels following a bimodal histogram, and the optimal threshold for segmenting this pattern enables maximizing its intervariance between the two classes. Using this optimal threshold, some statistics of the segmented classes, that is, their means, keep stable during phase shifting. Using these means of classes as nodes allows us to determine a linear transformation function by which the fluctuations of the fringe patterns in background intensities and modulations are corrected. Numerical simulation and experimental results demonstrate this method to be efficient and effective in improving the phase measuring accuracies with phase shifting technique. PMID- 26835641 TI - Dynamic structured-light measurement for wheel diameter based on the cycloid constraint. AB - Wheel diameter is a significant parameter related to the safety and comfort level of trains. The traditional circle fitting method can be sensitive to noise because of the small distribution of contact points. This paper proposes a structured-light measurement based on the cycloid constraint to obtain a wide distribution of contact points. The wheel is measured twice while running. The cycloid is used to integrate all the contact points to one circle. Simulations are implemented to analyze the possible errors, and the results are compared with the traditional method, which shows the method is more precise and has good stability against 3D reconstruction noise and out-of-roundness. The physical experiment also shows that the result is precise and robust. PMID- 26835642 TI - Direct and inverse problems of infrared tomography. AB - The problems of infrared tomography-direct (the modeling of measured functions) and inverse (the reconstruction of gaseous medium parameters)-are considered with a laboratory burner flame as an example of an application. The two measurement modes are used: active (ON) with an external IR source and passive (OFF) without one. Received light intensities on detectors are modeled in the direct problem or measured in the experiment whereas integral equations with respect to the absorption coefficient and Planck function (which yields the temperature profile of the medium) are solved in the inverse problem with (1) modeled and (2) measured received intensities as the input data. An axisymmetric flame and parallel scanning scheme of measurements considered in this work yield singular integral equations that are solved numerically using the generalized quadrature method, spline smoothing, and Tikhonov regularization. A software package in MATLAB has been developed. Two numerical examples-with modeled and real input data-were solved. The proposed methodology avoids the necessity of elaborate determination of the absorption coefficient by direct (point) measurements or calculation using spectroscopic databases (e.g., HITRAN/HITEMP). PMID- 26835643 TI - Ultrasound-guided Vascular Access: Visualizing the Tip of the Needle. PMID- 26835645 TI - Does Ondansetron Modify Sympathectomy Due to Subarachnoid Anesthesia?: Meta analysis, Meta-regression, and Trial Sequential Analysis. AB - BACKGROUND: Disagreement among many underpowered studies has led to an equivocal understanding of the efficacy of the 5-HT3 antagonist ondansetron in preventing the consequences of sympathectomy after subarachnoid anesthesia. The authors assessed the efficacy of ondansetron with respect to the overall quality and statistical power of the meta-analyses. METHODS: The authors used a standard and a newer method of meta-analysis, trial sequential analysis (TSA), to estimate adjusted CIs based on how much information has been accrued. They also used random-effects meta-analyses techniques, small trial bias assessment, selection models, sensitivity analyses, and the Grading of Recommendations on Assessment, Development, and Evaluation system. These results from the aforementioned techniques were compared, and importance of consideration of these factors was discussed. RESULTS: Fourteen randomized placebo-controlled trials (1,045 subjects) were identified and analyzed. By using conventional meta-analyses, the authors determined that ondansetron was associated with reduction in the incidence of hypotension (relative risk = 0.62 [95% CI, 0.46 to 0.83], P = 0.001; TSA-adjusted CI, 0.34 to 1.12; I = 60%, P = 0.002) and bradycardia (relative risk = 0.44 [95% CI, 0.26 to 0.73], P = 0.001; TSA-adjusted CI, 0.05 to 3.85; I = 0%, P = 0.84). However, the authors found indications of bias among these trials. TSAs demonstrated that the meta-analysis lacked adequate information size and did not achieve statistical significance when adjusted for sparse data and repetitive testing. The Grading of Recommendations on Assessment, Development, and Evaluation system showed that the results had low to very low quality of evidence. CONCLUSIONS: The analyses fail to confirm evidence that ondansetron reduces the incidence of hypotension and bradycardia after subarachnoid anesthesia due to the risk of bias and information sizes less than the required. As results from meta-analysis are given significant weight, it is important to carefully evaluate the quality of the evidence that is input. PMID- 26835644 TI - Variations in the Use of Perioperative Multimodal Analgesic Therapy. AB - BACKGROUND: Practice guidelines for perioperative pain management recommend that multimodal analgesic therapy should be used for all postsurgical patients. However, the proportion of patients who actually receive this evidence-based approach is unknown. The objective of this study was to describe hospital-level patterns in the utilization of perioperative multimodal analgesia. METHODS: Data for the study were obtained from the Premier Research Database. Patients undergoing below-knee amputation, open lobectomy, total knee arthroplasty, and open colectomy between 2007 and 2014 were included in the analysis. Patients were considered to have multimodal therapy if they received one or more nonopioid analgesic therapies. Mixed-effects logistic regression models were used to estimate the hospital-specific frequency of multimodal therapy use while adjusting for the case mix of patients and hospital characteristics and accounting for random variation. RESULTS: The cohort consisted of 799,449 patients who underwent a procedure at 1 of 315 hospitals. The mean probability of receiving multimodal therapy was 90.4%, with 95% of the hospitals having a predicted probability between 42.6 and 99.2%. A secondary analysis examined whether patients received two or more nonopioid analgesics, which gave an average predicted probability of 54.2%, with 95% of the hospitals having a predicted probability between 9.3 and 93.2%. CONCLUSIONS: In this large nationwide sample of surgical admissions in the United States, the authors observed tremendous variation in the utilization of multimodal therapy not accounted for by patient or hospital characteristics. Efforts should be made to identify why there are variations in the use of multimodal analgesic therapy and to promote its adoption in appropriate patients. PMID- 26835647 TI - Determination of factors responsible for the bioweathering of copper minerals from organic-rich copper-bearing Kupferschiefer black shale. AB - The aim of this study was to investigate the bioweathering of copper minerals present in the alkaline, copper-bearing and organic-rich Kupferschiefer black shale through the action of a consortium of indigenous lithobiontic, heterotrophic, neutrophilic bacteria isolated from this sedimentary rock. The involvement of microorganisms in the direct/enzymatic bioweathering of fossil organic matter of the rock was confirmed. As a result of bacterial activity, a spectrum of various organic compounds such as urea and phosphoric acid tributyl ester were released from the rock. These compounds indirectly act on the copper minerals occurring in the rock and cause them to weather. This process was reflected in the mobilization of copper, iron and sulfur and in changes in the appearance of copper minerals observed under reflected light. The potential role of identified enzymes in biodegradation of fossil organic matter and role of organic compounds released from black shale as a result of this process in copper minerals weathering was discussed. The presented results provide a new insight into the role of chemical compounds released by bacteria during fossil organic matter bioweathering potentially important in the cycling of copper and iron deposited in the sedimentary rock. The originality of the described phenomenon lies in the fact that the bioweathering of fossil organic matter and, consequently, of copper minerals occur simultaneously in the same environment, without any additional sources of energy, electrons and carbon. PMID- 26835646 TI - Effect of Inhalational Anesthetics and Positive-pressure Ventilation on Ultrasound Assessment of the Great Vessels: A Prospective Study at a Children's Hospital. AB - BACKGROUND: Bedside ultrasound has emerged as a rapid, noninvasive tool for assessment and monitoring of fluid status in children. The inferior vena cava (IVC) varies in size with changes in blood volume and intrathoracic pressure, but the magnitude of change to the IVC with inhalational anesthetic and positive pressure ventilation (PPV) is unknown. METHODS: Prospective observational study of 24 healthy children aged 1 to 12 yr scheduled for elective surgery. Ultrasound images of the IVC and aorta were recorded at five time points: awake; spontaneous ventilation with sevoflurane by mask; intubated with peak inspiratory pressure/positive end-expiratory pressure of 15/0, 20/5, and 25/10 cm H2O. A blinded investigator measured IVC/aorta ratios (IVC/Ao) and changes in IVC diameter due to respiratory variation (IVC-RV) from the recorded videos. RESULTS: Inhalational anesthetic decreased IVC/Ao (1.1 +/- 0.3 vs. 0.6 +/- 0.2; P < 0.001) but did not change IVC-RV (median, 43%; interquartile range [IQR], 36 to 58% vs. 46%; IQR, 36 to 66%; P > 0.99). The initiation of PPV increased IVC/Ao (0.64 +/- 0.21 vs. 1.16 +/- 0.27; P < 0.001) and decreased IVC-RV (median, 46%; IQR, 36 to 66% vs. 9%; IQR, 4 to 14%; P < 0.001). There was no change in either IVC/Ao or IVC-RV with subsequent incremental increases in peak inspiratory pressure/positive end-expiratory pressure (P > 0.99 for both). CONCLUSIONS: Addition of inhalational anesthetic affects IVC/Ao but not IVC-RV, and significant changes in IVC/Ao and IVC-RV occur with initiation of PPV in healthy children. Clinicians should be aware of these expected vascular changes when managing patients. Establishing these IVC parameters will enable future studies to better evaluate these measurements as tools for diagnosing hypovolemia or predicting fluid responsiveness. PMID- 26835648 TI - Spectroscopic characterization of changes of DOM deprotonation-protonation properties in water treatment processes. AB - The deprotonation-protonation properties of dissolved organic matter (DOM) in drinking water produced at critical treatment points were quantified using absorbance spectra in combination with DOM fractionation data. Analysis of differential spectra of DOM present in inlet, settled and filtered waters from two large treatment plants and their fractions were obtained. The data demonstrated the presence of six Gaussian bands largely associated with carboxylic and phenolic DOM functionalities. Properties of the protonation-active groups of DOM in raw and treated waters were further examined based on data of potentiometric titrations at pH from 2.5 to 10. Interpretation of the differential log-transformed absorbance at wavelength 350 nm (DlnA350) based on the NICA-Donnan model showed that the normalized concentrations of low- and high affinity protonation-active groups in residual DOMs increases as a result of water treatment. This was consistent with the results of DOM fractionation. This study demonstrates that changes of the composition and reactivity of DOM found in drinking water treatment sequences can be quantified based on the examination of their optical properties. PMID- 26835649 TI - Rapid and efficient removal/recovery of molybdenum onto ZnFe2O4 nanoparticles. AB - An efficient method for removing and recovering molybdenum (Mo) from water was developed by using ZnFe2O4 nanoparticles. The Mo adsorption displayed a nonlinear isotherm that fitted well with the Langmuir isotherm, showing limited adsorption sites on the surface of ZnFe2O4. The adsorption of Mo(VI) was dependent on solution pH. With increasing pH, the build-up of negative charges of both adsorbent and adsorbate led to enhanced electric repulsion between them. The K edge XANES spectra for the adsorbents collected after Mo adsorption revealed that Mo(VI) was the predominant oxidation state sorbed on ZnFe2O4, indicating that the reduction of Mo(VI) did not occur on ZnFe2O4. The different peak positions of k space and R-space shown in K-edge EXAFS spectra demonstrated that the adsorbed Mo could be bound on the surface or be slipped in the vacancy position of the ZnFe2O4 crystal. Importantly, Mo could be efficiently adsorbed from photoelectric industrial wastewater and these adsorbed Mo anions were rapidly replaced by OH(-) ions, implying the potential for Mo removing and recovering in industrial wastewater. PMID- 26835650 TI - On the interactions of human bone cells with Ti6Al4V thermally oxidized by means of laser shock processing. AB - We investigated a Ti6Al4V alloy modified by means of laser peening in the absence of sacrificial coatings. As a consequence of the temperature rise during laser focusing, melting and ablation generated an undulated surface that exhibits an important increase in the content of titanium oxides and OH- ions. Human mesenchymal stem cells and osteoblasts cultured on the oxidized alloy develop noticeable filopodia and lamellipodia. Their paxillin-stained focal adhesions are smaller than in cells attached to the untreated alloy and exhibit a marked loss of colocalization with the ends of actin stress fibers. An important imbalance of phosphorylation and/or dephosphorylation of the focal adhesion kinase is detected in cells grown on the oxidized alloy. Although these mechanisms of adhesion are deeply altered, the surface treatment does not affect cell attachment or proliferation rates on the alloy. Human mesenchymal stem cells cultured on the treated alloy in media containing osteogenic inducers differentiate towards the osteoblastic phenotype to a higher extent than those on the untreated surface. Also, the specific functions of human osteoblasts cultured on these media are enhanced on the treated alloy. In summary, laser peening tailors the Ti6Al4V surface to yield an oxidized layer with increased roughness that allows the colonization and activities of bone-lineage cells. PMID- 26835651 TI - Standardized methods to generate mock (spiked) clinical specimens by spiking blood or plasma with cultured pathogens. AB - AIMS: To demonstrate standardized methods for spiking pathogens into human matrices for evaluation and comparison among diagnostic platforms. METHODS AND RESULTS: This study presents detailed methods for spiking bacteria or protozoan parasites into whole blood and virus into plasma. Proper methods must start with a documented, reproducible pathogen source followed by steps that include standardized culture, preparation of cryopreserved aliquots, quantification of the aliquots by molecular methods, production of sufficient numbers of individual specimens and testing of the platform with multiple mock specimens. Results are presented following the described procedures that showed acceptable reproducibility comparing in-house real-time PCR assays to a commercially available multiplex molecular assay. CONCLUSIONS: A step by step procedure has been described that can be followed by assay developers who are targeting low prevalence pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: The development of diagnostic platforms for detection of low prevalence pathogens such as biothreat or emerging agents is challenged by the lack of clinical specimens for performance evaluation. This deficit can be overcome using mock clinical specimens made by spiking cultured pathogens into human matrices. To facilitate evaluation and comparison among platforms, standardized methods must be followed in the preparation and application of spiked specimens. PMID- 26835652 TI - The integumentary ultrastructure of Cryptocellus bordoni Dumitresco and Jurvara Bals, 1976 (Arachnida, Ricinulei). AB - Ricinulei is an order of Arachnida composed of rare and little known species. The species of Ricinulei possess a rich variety of fine integumentary structures that have been poorly investigated in a few species. Besides, several structures are still undescribed and their function not yet addressed. In this paper we provide a detailed study of the integumentary morphology of Cryptocellus bordoni Dumitresco and Jurvara-Bals, 1976 using Light and Scanning Electron Microscopy. We describe and present photos of the new and already known fine integumentary structures. We compare the new structures to those previously described for other Ricinulei species and discuss their taxonomic implications and the placement of C. bordoni in the genus Cryptocellus. PMID- 26835653 TI - Non-invasive sensing for food reassurance. AB - Consumers and governments are increasingly interested in the safety, authenticity and quality of food commodities. This has driven attention towards non-invasive sensing techniques used for rapid analyzing these commodities. This paper provides an overview of the state of the art in, and available alternatives for, food assurance based on non-invasive sensing techniques. The main food quality traits of interest using non-invasive sensing techniques are sensory characteristics, chemical composition, physicochemical properties, health protecting properties, nutritional characteristics and safety. A wide range of non-invasive sensing techniques, from optical, acoustical, electrical, to nuclear magnetic, X-ray, biosensor, microwave and terahertz, are organized according to physical principle. Some of these techniques are now in a period of transition between experimental and applied utilization and several sensors and instruments are reviewed. With continued innovation and attention to key challenges, such non invasive sensors and biosensors are expected to open up new exciting avenues in the field of portable and wearable wireless sensing devices and connecting with mobile networks, thus finding considerable use in a wide range of food assurance applications. The need for an appropriate regulatory framework is emphasized which acts to exclude unwanted components in foods and includes needed components, with sensors as part of a reassurance framework supporting regulation and food chain management. The integration of these sensor modalities into a single technological and commercial platform offers an opportunity for a paradigm shift in food reassurance. PMID- 26835654 TI - Influence of Temperature on the Colloidal Stability of Polymer-Coated Gold Nanoparticles in Cell Culture Media. AB - The temperature-dependence of the hydrodynamic diameter and colloidal stability of gold-polymer core-shell particles with temperature-sensitive (poly(N isopropylacrylamide)) and temperature-insensitive shells (polyallylaminine hydrochloride/polystyrensulfonate, poly(isobutylene-alt-maleic anhydride)-graft dodecyl) are investigated in various aqueous media. The data demonstrate that for all nanoparticle agglomeration, i.e., increase in effective nanoparticle size, the presence of salts or proteins in the dispersion media has to be taken into account. Poly(N-isopropylacrylamide) coated nanoparticles show a reversible temperature-dependent increase in size above the volume phase transition of the polymer shell when they are dispersed in phosphate buffered saline or in media containing protein. In contrast, the nanoparticles coated with temperature insensitive polymers show a time-dependent increase in size in phosphate buffered saline or in medium containing protein. This is due to time-dependent agglomeration, which is particularly strong in phosphate buffered saline, and induces a time-dependent, irreversible increase in the hydrodynamic diameter of the nanoparticles. This demonstrates that one has to distinguish between temperature- and time-induced agglomerations. Since the size of nanoparticles regulates their uptake by cells, temperature-dependent uptake of thermosensitive and non-thermosensitive nanoparticles by cells lines is compared. No temperature specific difference between both types of nanoparticles could be observed. PMID- 26835655 TI - Bifunctional Bronsted Base Catalyzes Direct Asymmetric Aldol Reaction of alpha Keto Amides. AB - The first enantioselective direct cross-aldol reaction of alpha-keto amides with aldehydes, mediated by a bifunctional ureidopeptide-based Bronsted base catalyst, is described. The appropriate combination of a tertiary amine base and an aminal, and urea hydrogen-bond donor groups in the catalyst structure promoted the exclusive generation of the alpha-keto amide enolate which reacted with either non-enolizable or enolizable aldehydes to produce highly enantioenriched polyoxygenated aldol adducts without side-products resulting from dehydration, alpha-keto amide self-condensation, aldehyde enolization, and isotetronic acid formation. PMID- 26835656 TI - Support systems of women with epilepsy in pregnancy: A retrospective needs assessment. AB - PURPOSE: To explore support systems for women with epilepsy (WWE) during pregnancy. METHODS: Audio-recorded, transcribed, semi-structured telephone interviews with WWE in pregnancy and following childbirth were coded using descriptive thematic analysis. RESULTS: Twelve women with epilepsy aged 21-37 years who received care during pregnancy in our epilepsy clinic from 2010 to 2013 were interviewed. Women identified three areas of support: immediate family, their specialist and group support. Some women felt unable to fully share health concerns with family members, but appreciated their support. Neurologists were perceived as reliable sources of support and information, but could be inaccessible. Support groups were seen as beneficial, but may heighten women's fear of epilepsy-related adverse events during pregnancy. CONCLUSION: This study highlights the use of support systems by WWE during pregnancy. The richness of the transcribed interviews provides valuable insight into the pregnancy experience of WWE and helps to direct future clinical and research goals and hypotheses. PMID- 26835657 TI - Novel antiviral effect of lithium chloride on mammalian orthoreoviruses in vitro. AB - Reovirus not only causes considerable economic loss in the swine industry of the United States and other countries, but also threatens the public health due to its zoonotic potential. According to previous reports, LiCl has antiviral activity against a number of viruses. The inhibitory effects of LiCl on reovirus life cycle in Vero cells were evaluated. The unpaired t-test and one-way ANOVA were used to analyze the differences between experimental groups. We first found that LiCl treatment significantly inhibited reovirus replication in a dose dependent manner. Furthermore, we found that this antiviral activity of LiCl targets the early stage of viral replication. LiCl could be a potential drug against reovirus infection. PMID- 26835658 TI - Phenotypic identification of Porphyromonas gingivalis validated with matrix assisted laser desorption/ionization time-of-flight mass spectrometry. AB - OBJECTIVE: Porphyromonas gingivalis is a major bacterial pathogen in human periodontitis. This study used matrix-assisted laser desorption/ionization time of-flight (MALDI-TOF) mass spectrometry to assess the accuracy of a rapid phenotypic identification scheme for detection of cultivable P. gingivalis in human subgingival plaque biofilms. METHODS: A total of 314 fresh cultivable subgingival isolates from 38 adults with chronic periodontitis were presumptively identified on anaerobically-incubated enriched Brucella blood agar primary isolation plates as P. gingivalis based on dark-pigmented colony morphology, lack of a brick-red autofluorescence reaction under long-wave ultraviolet light, and a positive CAAM fluorescence test for trypsin-like enzyme activity. Each presumptive P. gingivalis isolate, and a panel of other human subgingival bacterial species, were subjected to MALDI-TOF mass spectrometry analysis using a benchtop mass spectrometer equipped with software containing mass spectra for P. gingivalis in its reference library of bacterial protein profiles. A MALDI-TOF mass spectrometry log score of >=1.7 was required for species identification of the subgingival isolates. RESULTS: All 314 (100%) presumptive P. gingivalis subgingival isolates were confirmed as P. gingivalis with MALDI-TOF mass spectrometry analysis (Cohen's kappa coefficient = 1.0). MALDI-TOF mass spectrometry log scores between 1.7 and 1.9, and >=2.0, were found for 92 (29.3%) and 222 (70.7%), respectively, of the presumptive P. gingivalis clinical isolates. No other tested bacterial species was identified as P. gingivalis by MALDI-TOF mass spectrometry. CONCLUSIONS: Rapid phenotypic identification of cultivable P. gingivalis in human subgingival biofilm specimens was found to be 100% accurate with MALDI-TOF mass spectrometry. These findings provide validation for the continued use of P. gingivalis research data based on this species identification methodology. PMID- 26835659 TI - Non-oral gram-negative facultative rods in chronic periodontitis microbiota. AB - OBJECTIVE: The subgingival prevalence of gram-negative facultative rods not usually inhabiting or indigenous to the oral cavity (non-oral GNFR), as well as selected periodontal bacterial pathogens, were evaluated by culture in untreated and treated chronic periodontitis patients. METHODS: Subgingival biofilm specimens from 102 untreated and 101 recently treated adults with chronic periodontitis in the Netherlands were plated onto MacConkey III and Dentaid selective media with air-5% CO2 incubation for isolation of non-oral GNFR, and onto enriched Oxoid blood agar with anaerobic incubation for recovery of selected periodontal bacterial pathogens. Suspected non-oral GNFR clinical isolates were identified to a species level with the VITEK 2 automated system. RESULTS: A total of 87 (42.9%) out of 203 patients yielded subgingival non-oral GNFR. Patients recently treated with periodontal mechanical debridement therapy demonstrated a greater prevalence of non-oral GNFR (57.4% vs 28.4%, P < 0.0001), and a greater number of different non-oral GNFR species (23 vs 14 different species), than untreated patients. Sphingomonas paucimobilis was the most frequently isolated subgingival non-oral GNFR species. Several GNFR species normally found in animals and human zoonotic infections, and not previously detected in human subgingival biofilms, were recovered from some patients, including Bordetella bronchispetica, Pasteurella canis, Pasteurella pneumotropica and Neisseria zoodegmatis. Porphyromonas gingivalis and Tannerella forsythia were significantly associated with the presence of subgingival non-oral GNFR. CONCLUSIONS: A surprisingly high proportion of Dutch chronic periodontitis patients yielded cultivable non-oral GNFR in periodontal pockets, particularly among those recently treated with periodontal mechanical debridement therapy. Since non-oral GNFR species may resist mechanical debridement from periodontal pockets, and are often not susceptible to many antibiotics frequently used in periodontal practice, their subgingival presence may complicate periodontal treatment in species-positive patients and increase risk of potentially dangerous GNFR infections developing at other body sites. PMID- 26835660 TI - A systematic review of cognitive failures in daily life: Healthy populations. AB - Cognitive failures are minor errors in thinking reported by clinical and non clinical individuals during everyday life. It is not yet clear how subjectively reported cognitive failures relate to objective neuropsychological ability. We aimed to consolidate the definition of cognitive failures, outline evidence for the relationship with objective cognition, and develop a unified model of factors that increase cognitive failures. We conducted a systematic review of cognitive failures, identifying 45 articles according to the PRISMA statement. Failures were defined as reflecting proneness to errors in 'real world' planned thought and action. Vulnerability to failures was not consistently associated with objective cognitive performance. A range of stable and variable factors were linked to increased risk of cognitive failures. We conclude that cognitive failures measure real world cognitive capacity rather than pure 'unchallenged' ability. Momentary state may interact with predisposing trait factors to increase the likelihood of failures occurring. Inclusion of self-reported cognitive failures in objective cognitive research will increase the translational relevance of ability into more ecologically valid aspects of real world functioning. PMID- 26835661 TI - Modified Nucleotides for Discrimination between Cytosine and the Epigenetic Marker 5-Methylcytosine. AB - 5-Methyl-2'-deoxycytosine, the most common epigenetic marker of DNA in eukaryotic cells, plays a key role in gene regulation and affects various cellular processes such as development and carcinogenesis. Therefore, the detection of 5mC can serve as an important biomarker for diagnostics. Here we describe that modified dGTP analogues as well as modified primers are able to sense the presence or absence of a single methylation of C, even though this modification does not interfere directly with Watson-Crick nucleobase pairing. By screening several modified nucleotide scaffolds, O(6)-modified 2'-deoxyguanosine analogues were identified as discriminating between C and 5mC. These modified nucleotides might find application in site-specific 5mC detection, for example, through real-time PCR approaches. PMID- 26835662 TI - Apical Orbital Aspergillosis Complicating Giant Cell Arteritis. AB - A 75-year-old woman with new onset headaches and left vision loss, temporal scalp tenderness, and jaw claudication was found to have biopsy-proven giant cell arteritis (GCA). Despite treatment and improvement with prednisone, she later developed left orbital apex syndrome, and an orbital biopsy revealed aspergillosis. After antifungal treatment, extraocular motility improved although vision in the left eye remained no light perception. Clinicians should be aware that fungal orbital apex disease may mimic or complicate steroid-treated GCA. PMID- 26835663 TI - Retinal Ganglion Cell Loss Precedes Retinal Nerve Fiber Thinning in Nonarteritic Anterior Ischemic Optic Neuropathy. AB - BACKGROUND: Loss of retinal ganglion cell-inner plexiform layer (GCIPL) thickness has been shown in different optic neuropathies. In this study, we evaluated the capability of GCIPL analysis by optical coherence tomography (OCT) to detect early neuronal loss during the time course of nonarteritic anterior ischemic optic neuropathy (NAION). METHODS: Twenty-four patients with unilateral NAION participated in this prospective, comparative study. Affected and unaffected eyes underwent spectral domain OCT measurement of the retinal nerve fiber layer (RNFL), total macula, and GCIPL thicknesses. These measurements were recorded in the acute phase (within 7 days) and at 1, 3, and 6 months. RESULTS: At the initial presentation and 1, 3, and 6 months, the mean RNFL thickness in the NAION eyes was 236.5 MUm +/- 74.2, 157.1 MUm +/- 45.7, 61.4 MUm +/- 6.1, and 55.0 MUm +/- 19.5, respectively. Similar to RNFL, thinning of the mean total macular thickness in inner and outer rings started after 3 months and thicknesses decreased to 307.7 MUm +/- 15.3 and 273.1 MUm +/- 21.2 after 3 months and to 309.1 MUm +/- 15.0 and 273.4 MUm +/- 13.8 after 6 months, compared with unaffected contralateral eyes, respectively (all P < 0.0001). Thinning of the GCIPL was first evident in the affected NAION eyes at 1 month, and the mean inner and outer GCIPL thicknesses were 62.8 MUm +/- 14.6 and 53.9 MUm +/- 7.2 at 1 month in the NAION eyes compared with unaffected eyes (P < 0.001). After 3 and 6 months, the inner and outer GCIPL thicknesses were 51.1 MUm +/- 8.1 and 47.4 MUm +/- 5.31, and 50.6 MUm +/- 11.5 and 47.9 MUm +/- 5.6, respectively. CONCLUSIONS: Thinning of the GCIPL is first detectable at 1 month after NAION and persists for 3 months. GCIPL thinning occurs before RFNL thinning in NAION. PMID- 26835664 TI - Effects of formalin fixation and temperature on MR relaxation times in the human brain. AB - Post-mortem MRI of the brain is increasingly applied in neuroscience for a better understanding of the contrast mechanisms of disease induced tissue changes. However, the influence of chemical processes caused by formalin fixation and differences in temperature may hamper the comparability with results from in vivo MRI. In this study we investigated how formalin fixation and temperature affect T1, T2 and T2* relaxation times of brain tissue. Fixation effects were examined with respect to changes in water content and crosslinking. Relaxometry was performed in brain slices from five deceased subjects at different temperatures. All measurements were repeated after 190 days of formaldehyde immersion. The water content of unfixed and fixed tissue was determined using the wet-to-dry ratio following drying. Protein weight was determined with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Fixation caused a strong decrease of all relaxation times, the strongest effect being seen on T1, with a reduction of up to 76%. The temperature coefficient of T1 was lower in the fixed than unfixed tissue, which was in contrast to T2, where an increase of the temperature coefficient was observed following fixation. The reduction of the water content after fixation was in the range of 1-6% and thus not sufficient to explain the changes in relaxation time. Results from SDS-PAGE indicated a strong increase of the protein size above 260 kDa in all brain structures examined. Our results suggest that crosslinking induced changes of the macromolecular matrix are responsible for T1 shortening and a decreased temperature dependency. The relaxation times provided in this work should allow optimization of post-mortem MRI protocols for the brain. PMID- 26835665 TI - Natriuretic Peptides in Kawasaki Disease: the Myocardial Perspective. AB - Making a diagnosis of Kawasaki disease with certainty may be challenging, especially since the recognition of cases with incomplete diagnostic criteria and its consequences. In order to build the diagnostic case in daily practice, clinicians rely on clinical criteria established over four decades ago, aided by non specific laboratory tests, and above all inspired by experience. We have recently studied the diagnostic value of N-terminal pro B-type natriuretic peptide to improve the diagnostic certainty of cases with complete or incomplete clinical criteria. Our working hypothesis was based on the fact that myocarditis is present in nearly all Kawasaki disease patients supported by histology data. In this paper, we review these facts and the myocardial perspective from the diagnostic and the mechanistic standpoints. PMID- 26835666 TI - Soluble Human Epidermal Growth Factor Receptor 2 (sHER2) as a Potential Risk Assessment, Screening, and Diagnostic Biomarker of Lung Adenocarcinoma. AB - Lung cancer is the leading cause of cancer-related death in the United States. Here, we evaluated the potential clinical utility of soluble human epidermal growth factor receptor 2 (sHER2) for the risk assessment, screening, and diagnosis of non-small cell lung cancer (NSCLC) using an unmatched case-control study design. Serum sHER2 concentrations were measured by immunoassay in 244 primary NSCLC cases and 218 healthy controls. Wilcoxon rank-sum tests, logistic regression models, and receiver operating characteristic plots were used to assess whether sHER2 is associated with lung cancer. Median serum sHER2 concentrations are higher in patients with adenocarcinoma than squamous cell carcinoma regardless of gender, and sHER2 is a weak, independent biomarker of adenocarcinoma, but not of squamous cell carcinoma, adjusted for age and gender. The age-adjusted relative risk (odds) of adenocarcinoma is 3.95 (95% CI: 1.22, 12.81) and 7.93 (95% CI: 2.26, 27.82) greater for women and men with high sHER2 concentrations (>=6.60 ng/mL) vs. low sHER2 concentrations (<=1.85 ng/mL), respectively. When adjusted for each other, sHER2, age, and gender discern healthy controls from patients with primary adenocarcinomas of the lung with 85.9% accuracy. We conclude that even though serum sHER2 is not a strong, stand alone discriminatory biomarker of adenocarcinoma, sHER2 may be a useful, independent covariate in multivariate risk assessment, screening, and diagnostic models of lung cancer. PMID- 26835667 TI - A Review of Heating and Temperature Control in Microfluidic Systems: Techniques and Applications. AB - This review presents an overview of the different techniques developed over the last decade to regulate the temperature within microfluidic systems. A variety of different approaches has been adopted, from external heating sources to Joule heating, microwaves or the use of lasers to cite just a few examples. The scope of the technical solutions developed to date is impressive and encompasses for instance temperature ramp rates ranging from 0.1 to 2,000 degrees C/s leading to homogeneous temperatures from -3 degrees C to 120 degrees C, and constant gradients from 6 to 40 degrees C/mm with a fair degree of accuracy. We also examine some recent strategies developed for applications such as digital microfluidics, where integration of a heating source to generate a temperature gradient offers control of a key parameter, without necessarily requiring great accuracy. Conversely, Temperature Gradient Focusing requires high accuracy in order to control both the concentration and separation of charged species. In addition, the Polymerase Chain Reaction requires both accuracy (homogeneous temperature) and integration to carry out demanding heating cycles. The spectrum of applications requiring temperature regulation is growing rapidly with increasingly important implications for the physical, chemical and biotechnological sectors, depending on the relevant heating technique. PMID- 26835668 TI - TD-GC-MS Investigation of the VOCs Released from Blood Plasma of Dogs with Cancer. AB - An analytical TD-GC-MS method was developed and used for the assessment of volatile organic compounds (VOCs) released from the blood plasma of dogs with/without cancer. VOCs released from 40 samples of diseased blood and 10 control samples were compared in order to examine the difference between both sample groups that were showing qualitatively similar results independent from the disease's presence. However, mild disturbances in the spectra of dogs with cancer in comparison with the control group were observed, and six peaks (tentatively identified by comparison with mass spectral library as hexanal, octanal, toluene, 2-butanone, 1-octen-3-ol and pyrrole) revealed statistically significant differences between both sample groups, thereby suggesting that these compounds are potential biomarkers that can be used for cancer diagnosis based on the blood plasma TD-GC-MS analysis. Statistical comparison with the application of principal component analysis (PCA) provided accurate discrimination between the cancer and control groups, thus demonstrating stronger biochemical perturbations in blood plasma when cancer is present. PMID- 26835670 TI - Performance Evaluation of Fast Microfluidic Thermal Lysis of Bacteria for Diagnostic Sample Preparation. AB - Development of new diagnostic platforms that incorporate lab-on-a-chip technologies for portable assays is driving the need for rapid, simple, low cost methods to prepare samples for downstream processing or detection. An important component of the sample preparation process is cell lysis. In this work, a simple microfluidic thermal lysis device is used to quickly release intracellular nucleic acids and proteins without the need for additional reagents or beads used in traditional chemical or mechanical methods (e.g., chaotropic salts or bead beating). On-chip lysis is demonstrated in a multi-turn serpentine microchannel with external temperature control via an attached resistive heater. Lysis was confirmed for Escherichia coli by fluorescent viability assay, release of ATP measured with bioluminescent assay, release of DNA measured by fluorometry and qPCR, as well as bacterial culture. Results comparable to standard lysis techniques were achievable at temperatures greater than 65 degrees C and heating durations between 1 and 60 s. PMID- 26835671 TI - Strain Elastography Ultrasound: An Overview with Emphasis on Breast Cancer Diagnosis. AB - Strain elastography (SE), which estimates tissue strain, is an adjunct to the conventional ultrasound B-mode examination. We present a short introduction to SE and its clinical use. Furthermore, we present an overview of the 10 largest studies performed on the diagnostic accuracy of SE in breast cancer diagnostics. Eight of 10 studies presented data for both SE and B-mode imaging. Seven studies showed better specificity and accuracy for SE than for B-mode imaging in breast cancer diagnosis. Four studies showed an increase in specificity and accuracy when combining B-mode imaging with SE. The ways of combining B-mode imaging with SE in the diagnosis of breast cancer differed between the five studies. We believe that further studies are needed to establish an optimal algorithm for the combination of B-mode ultrasound and SE in breast cancer. PMID- 26835669 TI - MicroRNAs as Biomarkers in Cancer. AB - MicroRNAs (miRNAs) are small non-coding RNA molecules, which in recent years have emerged to have enormous potential as biomarkers. Recently, there have been significant developments in understanding miRNA biogenesis, their regulatory mechanisms and role in disease process, and their potential as effective therapies. The identification of miRNAs as biomarkers provides possibilities for development of less or non-invasive and more specific methods for monitoring tumor growth and progression. This review summarizes the recent developments in methods to detect and quantitate miRNAs in body fluids and their applications as biomarkers in cancers. The prospect of miRNAs as potential diagnostic and prognostic biomarkers with clinical applications is significant as more evidence points to their central role in cancer pathobiology. PMID- 26835674 TI - Analysis of Predictive Values Based on Individual Risk Factors in Multi-Modality Trials. AB - The accuracy of diagnostic tests with binary end-points is most frequently measured by sensitivity and specificity. However, from the clinical perspective, the main purpose of a diagnostic agent is to assess the probability of a patient actually being diseased and hence predictive values are more suitable here. As predictive values depend on the pre-test probability of disease, we provide a method to take risk factors influencing the patient's prior probability of disease into account, when calculating predictive values. Furthermore, approaches to assess confidence intervals and a methodology to compare predictive values by statistical tests are presented. Hereby the methods can be used to analyze predictive values of factorial diagnostic trials, such as multi-modality, multi reader-trials. We further performed a simulation study assessing length and coverage probability for different types of confidence intervals, and we present the R-Package facROC that can be used to analyze predictive values in factorial diagnostic trials in particular. The methods are applied to a study evaluating CT angiography as a noninvasive alternative to coronary angiography for diagnosing coronary artery disease. Hereby the patients' symptoms are considered as risk factors influencing the respective predictive values. PMID- 26835672 TI - When Medicine Meets Engineering-Paradigm Shifts in Diagnostics and Therapeutics. AB - During the last two decades, the manufacturing techniques of microfluidics-based devices have been phenomenally advanced, offering unlimited potential for bio medical technologies. However, the direct applications of these technologies toward diagnostics and therapeutics are still far from maturity. The present challenges lay at the interfaces between the engineering systems and the biocomplex systems. A precisely designed engineering system with narrow dynamic range is hard to seamlessly integrate with the adaptive biological system in order to achieve the design goals. These differences remain as the roadblock between two fundamentally non-compatible systems. This paper will not extensively review the existing microfluidic sensors and actuators; rather, we will discuss the sources of the gaps for integration. We will also introduce system interface technologies for bridging the differences to lead toward paradigm shifts in diagnostics and therapeutics. PMID- 26835673 TI - Development of MicroRNA Therapeutics for Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is the most common form of liver cancer and is the third leading cause of cancer-related deaths worldwide. Treatment options for HCC are very limited, as it is often diagnosed at a late stage. Recent studies have demonstrated that microRNAs (miRNAs), a class of non-coding RNAs, are aberrantly expressed in HCC. Some of these were shown to be functionally involved in carcinogenesis and tumor progression, suggesting that miRNAs can serve as novel molecular targets for HCC therapy. Several promising studies have recently demonstrated the therapeutic potential of miRNAs in animal models and in reducing the viral load in hepatitis C patients. In this review, these advances and strategies for modulating miRNAs for in vivo therapeutic delivery and replacement therapy are discussed. PMID- 26835675 TI - Catecholamines and Neurodegeneration in Parkinson's Disease-From Diagnostic Marker to Aggregations of alpha-Synuclein. AB - Parkinson's disease is the second most prevalent disease of the brain. It is characterized by midbrain dopaminergic neuronal degeneration accompanied by Lewy bodies, intra-cytoplasmic neuronal inclusions that consist mainly of alpha synuclein. The cardinal motor features are muscular rigidity, bradykinesia, and resting tremor and, in advanced cases, postural instability. Symptoms are relieved by dopamine replacement therapy, but progress slowly. Clinical diagnosis is made according to medical history, neurological examinations and the response to anti-Parkinsonian drugs. There are no laboratory tests for diagnosis of the disease; however, for development of disease-modifying treatment, early diagnosis by objective laboratory test is required. Recently, postsynaptic sympathetic norepinephrine nerve terminals were found to be degenerated as well as mesencephalic dopaminergic neurons. Cardiac norepinephrine denervation can be seen by meta-iodine-benzyl guanidine scintigraphy, and may be a reliable diagnostic marker. Degeneration of norepinephrinergic and dopaminergic neurons suggests that catecholamines may play a central role in the neurodegeneration in Parkinson's disease. Recently several studies showed that alpha-synuclein aggregates in cells exposed to dopamine. Here, we review findings relating to an early diagnostic marker for detecting degeneration of the peripheral sympathetic nerves, and propose the hypothesis that catecholamines cause alpha-synuclein to aggregate and play an important role in disease pathogenesis. PMID- 26835676 TI - Diagnosis of Upper and Lower Respiratory Tract Bacterial Infections with the Use of Multiplex PCR Assays. AB - The investigation of respiratory infections by molecular techniques provides important information about the epidemiology of respiratory disease, especially during the post-vaccination era. The objective of the present study was the detection of bacterial pathogens directly in clinical samples from patients with upper and lower respiratory tract infections using multiplex polymerase chain reaction (PCR) assays developed in our laboratory. Clinical samples taken over a three-year period (2007-2009) and obtained from 349 patients (adults (n = 66); children (n = 283)) with signs and symptoms of certain upper or lower respiratory tract infections, consisted of: bronchoalveolar lavages (BAL, n = 83), pleural fluids (n = 29), and middle-ear aspirates (n = 237). Overall, 212 samples (61%) were confirmed by culture and/or PCR. Among the positive samples, Streptococcus pneumoniae (mainly serotype 3) was predominant (104/212; 49.0%), followed by non typable Haemophilus influenzae (NTHi) 59/212; 27.8%) and Streptococcus pyogenes (47/212; 22%). Haemophilus influenzae type b was detected in only three samples. The underlying microbiology of respiratory infections is gradually changing in response to various selective pressures, such as vaccine use and antibiotic consumption. The application of multiplex PCR (mPCR) assays is particularly useful since it successfully identified the microorganisms implicated in acute otitis media or lower respiratory tract infections in nearly 75% of patients with a positive result compared to conventional cultures. Non-culture identification of the implicated pneumococcal serotypes is also an important issue for monitoring pneumococcal infections in the era of conjugate pneumococcal vaccines. PMID- 26835677 TI - Can Coronary Artery Involvement in Kawasaki Disease be Predicted? AB - BACKGROUND: Coronary artery involvement is seen in approximately 15-20% of children with Kawasaki disease. There is conflicting literature regarding the clinical and laboratory findings associated with coronary artery involvement. In this retrospective study, we attempt identification of predictive factors for coronary artery involvement at our institute and review the existing literature. METHODS AND RESULTS: A review of 203 patients (65% males) with Kawasaki disease was performed, of whom 33 (16.3%) had coronary artery involvement. High erythrocyte sedimentation rate, high platelet count, low hematocrit, low albumin levels, and refractory Kawasaki disease showed significant association with coronary artery involvement. High erythrocyte sedimentation rate and refractory Kawasaki disease were found to be independent predictors of coronary artery involvement. Review of literature suggested a wide range of coronary involvement (<5% to >60%), and highly conflicting clinical and laboratory associations. CONCLUSION: It remains difficult to accurately determine risk of coronary artery involvement, although some laboratory markers may provide information that is helpful for parental counseling and clinical follow up. Future identification of novel biomarkers and host predispositions may further our understanding of coronary artery risks and help personalize therapy for Kawasaki disease. PMID- 26835679 TI - Computed Tomography (CT) Perfusion in Abdominal Cancer: Technical Aspects. AB - Computed Tomography (CT) Perfusion is an evolving method to visualize perfusion in organs and tissue. With the introduction of multidetector CT scanners, it is now possible to cover up to 16 cm in one rotation, and thereby making it possible to scan entire organs such as the liver with a fixed table position. Advances in reconstruction algorithms make it possible to reduce the radiation dose for each examination to acceptable levels. Regarding abdominal imaging, CT perfusion is still considered a research tool, but several studies have proven it as a reliable non-invasive technique for assessment of vascularity. CT perfusion has also been used for tumor characterization, staging of disease, response evaluation of newer drugs targeted towards angiogenesis and as a method for early detection of recurrence after radiation and embolization. There are several software solutions available on the market today based on different perfusion algorithms. However, there is no consensus on which protocol and algorithm to use for specific organs. In this article, the authors give an introduction to CT perfusion in abdominal imaging introducing technical aspects for calculation of perfusion parameters, and considerations on patient preparation. This article also contains clinical cases to illustrate the use of CT perfusion in abdominal imaging. PMID- 26835678 TI - A Rapid, Multiplexed, High-Throughput Flow-Through Membrane Immunoassay: A Convenient Alternative to ELISA. AB - This paper describes a rapid, high-throughput flow-through membrane immunoassay (FMIA) platform. A nitrocellulose membrane was spotted in an array format with multiple capture and control reagents for each sample detection area, and assay steps were carried out by sequential aspiration of sample and reagents through each detection area using a 96-well vacuum manifold. The FMIA provides an alternate assay format with several advantages over ELISA. The high surface area of the membrane permits high label concentration using gold labels, and the small pores and vacuum control provide rapid diffusion to reduce total assay time to ~30 min. All reagents used in the FMIA are compatible with dry storage without refrigeration. The results appear as colored spots on the membrane that can be quantified using a flatbed scanner. We demonstrate the platform for detection of IgM specific to lipopolysaccharides (LPS) derived from Salmonella Typhi. The FMIA format provides analytical results comparable to ELISA in less time, provides integrated assay controls, and allows compensation for specimen-to-specimen variability in background, which is a particular challenge for IgM assays. PMID- 26835680 TI - Quantification of Right and Left Ventricular Function in Cardiac MR Imaging: Comparison of Semiautomatic and Manual Segmentation Algorithms. AB - The purpose of this study was to evaluate the performance of a semiautomatic segmentation method for the anatomical and functional assessment of both ventricles from cardiac cine magnetic resonance (MR) examinations, reducing user interaction to a "mouse-click". Fifty-two patients with cardiovascular diseases were examined using a 1.5-T MR imaging unit. Several parameters of both ventricles, such as end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF), were quantified by an experienced operator using the conventional method based on manually-defined contours, as the standard of reference; and a novel semiautomatic segmentation method based on edge detection, iterative thresholding and region growing techniques, for evaluation purposes. No statistically significant differences were found between the two measurement values obtained for each parameter (p > 0.05). Correlation to estimate right ventricular function was good (r > 0.8) and turned out to be excellent (r > 0.9) for the left ventricle (LV). Bland-Altman plots revealed acceptable limits of agreement between the two methods (95%). Our study findings indicate that the proposed technique allows a fast and accurate assessment of both ventricles. However, further improvements are needed to equal results achieved for the right ventricle (RV) using the conventional methodology. PMID- 26835681 TI - Overview of Five-Years of Experience Performing Non-Invasive Fetal Sex Assessment in Maternal Blood. AB - Since the discovery of the presence of fetal DNA in maternal blood, non-invasive fetal sex determination has been the test most widely translated into clinical practice. To date there is no agreement between the different laboratories performing such tests in relation to which is the best protocol. As a consequence there are almost as many protocols as laboratories offering the service, using different methodologies and thus obtaining different diagnostic accuracies. By the end of 2007, after a validation study performed in 316 maternal samples collected between the 5th and 12th week of gestation, the fetal sex determination was incorporated into clinical practice in our Service. The test is performed in the first trimester of pregnancy, and it is offered as part of the genetic counseling process for couples at risk of X-linked disorders. As a general rule and in order to avoid misdiagnosis, two samples at different gestational ages are tested per patient. The analysis is performed by the study of the SRY gene by RT PCR. Two hundred and twenty six pregnancies have been tested so far in these 5 years. Neither false positives nor false negatives diagnoses have been registered, thus giving a diagnostic accuracy of 100%. PMID- 26835683 TI - Temperature Control Function of the Choroid May Be the Reason for the Increase in Choroidal Thickness during the Acute Phase of Familial Mediterranean Fever. PMID- 26835684 TI - Correction: Social Network Analysis As a Tool for Research Policy. PMID- 26835682 TI - Non-Invasive Screening Tools for Down's Syndrome: A Review. AB - Down's syndrome (DS) is the most common genetic cause of developmental delay with an incidence of 1 in 800 live births, and is the predominant reason why women choose to undergo invasive prenatal diagnosis. However, as invasive tests are associated with around a 1% risk of miscarriage new non-invasive tests have been long sought after. Recently, the most promising approach for non-invasive prenatal diagnosis (NIPD) has been provided by the introduction of next generation sequencing (NGS) technologies. The clinical application of NIPD for DS detection is not yet applicable, as large scale validation studies in low-risk pregnancies need to be completed. Currently, prenatal screening is still the first line test for the detection of fetal aneuploidy. Screening cannot diagnose DS, but developing a more advanced screening program can help to improve detection rates, and therefore reduce the number of women offered invasive tests. This article describes how the prenatal screening program has developed since the introduction of maternal age as the original "screening" test, and subsequently discusses recent advances in detecting new screening markers with reference to both proteomic and bioinformatic techniques. PMID- 26835685 TI - [Hereditary metabolic diseases with onset in adulthood. Early and correct treatment of acute symptoms can be life-saving]. AB - Inherited metabolic diseases usually present in the neonatal period or before school age. A growing portion of the disorders can be treated successfully, and an increasing number of patients are now treated in adult medicine. Several of the disorders also exist as attenuated variants without distinct symptoms in childhood. They can present as an acute onset event during metabolic stress in adulthood. We describe three patients with acute clinical decompensation in adulthood with severe sequelae and propose investigations to help diagnose such patients. One patient was unconscious from ammonia intoxication and developed severe neurological sequelae because of a defect in the urea cycle. A second patient had seizures caused by a defect in the conversion of homocysteine to methionine, resulting in lack of S-adenosylmethionine. A third patient had a stroke and grossly elevated homocysteine caused by undiagnosed homocystinuria. Recently there have been dramatic improvements in diagnostic methods, and new therapies are continuously being developed. Knowledge of these disorders is therefore of increasing importance also in adult medicine. PMID- 26835686 TI - [Many people over 80 years had been able to get care outside the hospital]. AB - Ageing populations and higher ambitions continuously drive healthcare costs in Sweden and worldwide. During the last two decades, downsizing hospital bed capacity has been the strategy for cutting expenditure in the Swedish healthcare system. However, the lack of implementation of new and viable outpatient alternatives has led to a widespread overcrowding problem in Swedish hospitals and emergency departments. The present study was conducted as a survey in hospital wards at two emergency hospitals in southwestern Sweden. Study aims were to assess the causes of hospitalization and indications for continuing in hospital care in hospitalized geriatric patients (>80 years). The study shows that a very small number of patients are admitted barely because of social factors; however, there is a significant group where hospitalization is due to both social and medical factors. A large group of hospitalized patients over 80 year (37%) could receive their care outside the emergency hospital. About 30% of hospitalized patients are waiting for planning, and the majority of them waiting for social action and planning. Older patients with multiple diseases require healthcare but not hospitalization to the present extent. We should focus on developing additional forms of healthcare since avoidable hospitalization is a high cost for the society, but above all a risk for the individual. PMID- 26835688 TI - [Not Available]. PMID- 26835687 TI - [Acute cutaneous symptom complex with subsequent cataract. The internet drug MT 45 may be the cause]. AB - The number of new psychoactive substances ("NPS") sold by online drug vendors ("Internet drugs") shows a steady increase. Over a short time period in 2013 2014, three Swedish men aged 23-34 years with suspected drug use experienced similar but unusual clinical symptoms including loss and depigmentation of hair, widespread folliculitis and dermatitis, painful intertriginous dermatitis, dryness of eyes, and elevated liver enzymes. Two also had lines of discoloration across the nails ("Mees' lines") of the fingers and toes. The symptoms gradually disappeared over time. However, two of them subsequently developed severe bilateral secondary cataracts requiring surgery. Blood tests for NPS performed within the Swedish STRIDA project demonstrated intake of the synthetic opioid MT 45, a piperazine derivative originally synthesized as a therapeutic drug candidate in the 1970s, in all three patients, suggesting this as a possible common causative agent. These clinical cases highlight the importance for physicians to consider the increasing number of untested recreational drugs as a potential cause of unusual clinical symptoms. PMID- 26835689 TI - [About mental illness and evidence]. PMID- 26835690 TI - [Incident reporting analyses in suicides--important in a learning organization]. PMID- 26835691 TI - [Not Available]. PMID- 26835692 TI - [Stress and brain injuries]. PMID- 26835693 TI - [Not Available]. PMID- 26835694 TI - [Not Available]. PMID- 26835695 TI - [Continued health inequalities in northeastern Gothenburg--time to rethink]. PMID- 26835696 TI - [Karolinska is the Chernobyl of ethics]. PMID- 26835697 TI - [What responsibility does co-authors have?]. PMID- 26835698 TI - Syndecan-4 Signaling Is Required for Exercise-Induced Cardiac Hypertrophy. AB - Cardiac hypertrophy can be broadly classified as either physiological or pathological. Physiological stimuli such as exercise cause adaptive cardiac hypertrophy and normal heart function. Pathological stimuli including hypertension and aortic valvular stenosis cause maladaptive cardiac remodeling and ultimately heart failure. Syndecan-4 (synd4) is a transmembrane proteoglycan identified as being involved in cardiac adaptation after injury, but whether it takes part in physiological cardiac hypertrophy is unclear. We observed upregulation of synd4 in exercise-induced hypertrophic myocardium. To evaluate the role of synd4 in the physiological form of cardiac hypertrophy, mice lacking synd4 (synd4-/-) were exercised by swimming for 4 wks. Ultrasonic cardiogram (UCG) and histological analysis revealed that swimming induced the hypertrophic phenotype but was blunted in synd4-/- compared with wild-type (WT) mice. The swimming-induced activation of Akt, a key molecule in physiological hypertrophy was also more decreased than in WT controls. In cultured cardiomyocytes, synd4 overexpression could induce cell enlargement, protein synthesis and distinct physiological molecular alternation. Akt activation also was observed in synd4 overexpressed cardiomyocytes. Furthermore, inhibition of protein kinase C (PKC) prevented the synd4-induced hypertrophic phenotype and Akt phosphorylation. This study identified an essential role of synd4 in mediation of physiological cardiac hypertrophy. PMID- 26835699 TI - Combined Administration of Human Ghrelin and Human Growth Hormone Attenuates Organ Injury and Improves Survival in Aged Septic Rats. AB - Sepsis is a major healthcare concern, especially in the elderly population. The use of an animal model closely resembling clinical conditions in this population may provide a better prediction in translating bench studies to the bedside. Ghrelin inhibits sympathetic nerve activity and inflammation in young septic animals; however, aged animals become hyporesponsive to ghrelin. In this study, we evaluated the efficacy of combined human ghrelin and growth hormone (GH) for sepsis treatment in the elderly utilizing a clinically relevant animal model of sepsis. Male Fischer 344 rats 22 to 24 months old were subjected to cecal ligation and puncture (CLP). Human ghrelin plus GH or vehicle (normal saline) was administered subcutaneously at 5 h after CLP. At 20 h after CLP, blood and tissue samples were collected for various analyses. Combined treatment attenuated serum levels of lactate, lactate dehydrogenase, creatinine, blood urea nitrogen, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in aged septic rats. The integrity of the microscopic structure in the lungs, liver and kidneys was well preserved after treatment. Expression of IL-6, TNF-alpha, macrophage inflammatory protein-2 and keratinocyte-derived chemokine as well as myeloperoxidase activity and caspase-3 activation were significantly reduced in the lungs and liver of treated rats. Moreover, treated rats showed an improvement in cardiovascular function and increased expression of ghrelin receptor and c-fos in the brainstem. Finally, the 10-d survival of aged septic rats was increased from 29% to 64% after combined treatment and was associated with less body weight loss. Our findings warrant the development of combined human ghrelin and GH for sepsis treatment in the geriatric population. PMID- 26835700 TI - Hyperuricaemia: contributions of urate transporter ABCG2 and the fractional renal clearance of urate. AB - OBJECTIVE: To investigate the contributions towards hyperuricaemia of known risk factors, focusing on fractional (renal) clearance of urate (FCU) and variation in the ATP-binding cassette transporter, sub-family G 2 (ABCG2) gene. METHODS: The contributions of age, sex, ancestry, Q141K genotype for ABCG2, FCU, sugar sweetened beverage and alcohol consumption, metabolic syndrome disorders and measures of renal function to the risk of hyperuricaemia were evaluated by comparing hyperuricaemic (serum urate>=0.42 mmol/L, n=448) with normouricaemic (serum urate<0.42 mmol/L, n=344) participants using stepwise logistic regression. Model performance was evaluated using the area under the receiver operator characteristic curve (AUROC). RESULTS: ABCG2 genotype, FCU, male sex, body mass index, serum triglyceride concentrations, estimated glomerular filtration rate and consumption of alcohol were the best predictors of hyperuricaemia (AUROC 0.90, 81% accuracy). Homozygosity in the 141K variant for ABCG2 conferred an adjusted OR of 10.5 for hyperuricaemia (95% CI 2.4 to 46.2). For each 1% decrease of FCU, the adjusted OR increased by 51% (OR 1.51, 95% CI 1.37 to 1.66). There was no association between ABCG2 genotype and FCU (r=0.02, p=0.83). CONCLUSIONS: The ABCG2 141K variant and the FCU contribute strongly but independently to hyperuricaemia. These findings provide further evidence for a significant contribution of ABCG2 to extra-renal (gut) clearance of urate. PMID- 26835702 TI - Electron Detachment and Subsequent Structural Changes of Water Clusters. AB - A cost-effective equation of motion coupled cluster method, EOMIP-CCSD(2), is used to investigate vertical and adiabatic ionization potential as well as ionization-induced structural changes of water clusters and compared with CCSD(T), CASPT2, and MP2 methods. The moderate N(5) scaling and low storage requirement yields EOMIP-CCSD(2) calculation feasible even for reasonably large molecules and clusters with accuracy comparable to CCSD(T) method at much cheaper computational cost. Our calculations shed light on the authenticity of EOMIP CCSD(2) results and establish a reliable method to study of ionization energy of molecular clusters. We have further investigated the performance of several classes of DFT functionals for ionization energies of water clusters to benchmark the results and to get a reliable functionals for the same. PMID- 26835701 TI - Assessment of fluorinated steroids to avert progression and mortality in anti SSA/Ro-associated cardiac injury limited to the fetal conduction system. AB - OBJECTIVES: Extension of disease beyond the atrioventricular (AV) node is associated with increased mortality in cardiac neonatal lupus (NL). Treatment of isolated heart block with fluorinated steroids to prevent disease progression has been considered but published data are limited and discordant regarding efficacy. This study evaluated whether fluorinated steroids given to manage isolated advanced block prevented development of disease beyond the AV node and conferred a survival benefit. METHODS: In this retrospective study of cases enrolled in the Research Registry for NL, inclusion was restricted to anti-SSA/Ro-exposed cases presenting with isolated advanced heart block in utero who either received fluorinated steroids within 1 week of detection (N=71) or no treatment (N=85). Outcomes evaluated were: development of endocardial fibroelastosis, dilated cardiomyopathy and/or hydrops fetalis; mortality and pacemaker implantation. RESULTS: In Cox proportional hazards regression analyses, fluorinated steroids did not significantly prevent development of disease beyond the AV node (adjusted HR=0.90; 95% CI 0.43 to 1.85; p=0.77), reduce mortality (HR=1.63; 95% CI 0.43 to 6.14; p=0.47) or forestall/prevent pacemaker implantation (HR=0.87; 95% CI 0.57 to 1.33; p=0.53). No risk factors for development of disease beyond the AV node were identified. CONCLUSIONS: These data do not provide evidence to support the use of fluorinated steroids to prevent disease progression or death in cases presenting with isolated heart block. PMID- 26835703 TI - Stretchable Polyurethane Sponge Scaffold Strengthened Shear Stiffening Polymer and Its Enhanced Safeguarding Performance. AB - A simple and scalable "dip and dry" method was developed for fabricating stretchable polyurethane sponge-based polymer composite with excellent shear stiffening effect, creep resisting and adhesion property. The stiffness of the composite was tunable, the storage modulus (G') could automatically increase 3 orders of magnitude with the increasing of shear frequency, and the G'max could reach to as high as 1.55 MPa. Importantly, the composite with ideal damping capacity reduced the impact force by 2 orders of magnitude even under 26 cycles of consecutive dynamic impact loading with no obvious mechanical degradation. Moreover, an enhancing mechanism was proposed and it was found the "B-O cross bond" and the entanglement of polymer chains were attributed to the shear stiffening characteristic. Finally, the excellent adhesion ability and hydrophobicity guarantee the composite with reliable mechanical performance and longer lifespan. PMID- 26835705 TI - Engineering the Morphology and Configuration of Ternary Heterostructures for Improving Their Photocatalytic Activity. AB - Heteronanomaterials composed of suitable semiconductors enable the direct conversion from solar power into clean and renewable energy. Ternary heterostructures with appropriate configuration and morphology possess rich and varied properties, especially for improving the photocatalytic activity and stability synchronously. However, suitable ternary heterostructure prototypes and facile while effective strategy for modulating their morphology and configuration are still scarce. Herein, various ternary ZnS-CdS-Zn(1-x)Cd(x)S heterostructures with tunable morphology (0 to 2 D) and semiconductor configurations (randomly distributed, interface mediated, and quantum dots sensitized core@shell heterostructures) were facilely synthesized via one-pot hydrothermal method resulting from the different molecular structures of the amine solvents. Semiconductor morphology, especially configuration of the ternary heterostructure, shows dramatic effect on their photocatalytic activity. The CdS sensitized porous Zn(1-x)CdxS@ZnS core@shell takes full advantage of ZnS, Zn(1 x)Cd(x)S and CdS and shows the maximal photocatalytic H2-production rate of 100.2 mmol/h/g and excellent stability over 30 h. This study provides some guidelines for the design and synthesis of high-performance ternary heterostructure via modulation of semiconductor configuration and morphology using one-pot method. PMID- 26835704 TI - Practical Ni-Catalyzed Aryl-Alkyl Cross-Coupling of Secondary Redox-Active Esters. AB - A new transformation is presented that enables chemists to couple simple alkyl carboxylic acids with aryl zinc reagents under Ni-catalysis. The success of this reaction hinges on the unique use of redox-active esters that allow one to employ such derivatives as alkyl halides surrogates. The chemistry exhibits broad substrate scope and features a high degree of practicality. The simple procedure and extremely inexpensive nature of both the substrates and pre-catalyst (NiCl2.6H2O, ca. $9.5/mol) bode well for the immediate widespread adoption of this method. PMID- 26835706 TI - The effects of PK11195 on meningioma was associated with allopregnanolone biosynthesis, which was mediated by translocator protein 18 KDa. AB - Meningioma is one of the common brain tumors in adults. It had been shown that the allopregnanolone biosynthesis was associated with tumorigenesis and PK11195, the translocator protein 18 KDa (TSPO) antagonist, had the effects of the allopregnanolone biosynthesis. However, little is known about the association between the effects of PK11195 on meningioma and the allopregnanolone biosynthesis. To evaluate this, the meningioma cell line IOMM-LEE was applied. Cell viability and proliferation were determined by CCK-8 assay. The IC50 of PK11195 on the IOMM-LEE was 1.505 +/- 0.08 nM. The cell viability and proliferation of AC-5216 (TSPO selective ligand, 2 and 4 nM) was blocked by PK11195 (1.5 nM). Further, we evaluated the role of allopregnanolone biosynthesis in the effects of TSPO on meningioma. Enzyme-Linked ImmunoSorbent Assay (ELISA) was used in the measurement of the allopregnanolone level. It showed that the allopregnanolone level was increased by AC-5216 (2 and 4 nM) and the increase was reversed by PK11195 (1.5 nM). Collectedly, it firstly indicated that the effects of PK11195 on meningioma were relevant to the decrease of allopregnanolone biosynthesis, which was mediated by TSPO. PMID- 26835707 TI - Prognostic value of hedgehog signaling pathway in digestive system cancers: A systematic review and meta-analysis. AB - BACKGROUND: The Hedgehog (Hh) signaling pathway has recently been reported to be associated with the prognosis of digestive system cancers. However, the results are inconsistent. OBJECTIVE: This study aimed to investigate the association between Hh pathway components and survival outcomes in patients with digestive system cancers. METHODS: We conducted a comprehensive retrieval in PubMed, EMBASE and Cochrane library for relevant literatures until May 1st, 2015. The pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) with 95% confidence intervals (CIs) were calculated to clarify the prognostic value of Hh pathway components, including Shh, Gli1, Gli2, Smo and Ptch1. RESULTS: A total of 16 eligible articles with 3222 patients were included in the meta-analysis. Pooled HR suggested that over-expression of Shh and Gli1 were both associated with poor OS (HR = 1.87, 95% CI: 1.14-3.07 and HR = 1.96, 95% CI: 1.66 2.32, respectively) and DFS (HR = 2.37, 95% CI: 1.19-4.72 and HR = 2.18, 95% CI: 1.61-2.96, respectively). In addition, over-expression of Smo was associated with poor DFS (HR = 1.38, 95% CI: 1.08-1.75). CONCLUSIONS: This study reveals that over-expressed Hh pathway components, including Shh, Gli1 and Smo, are associated with poor prognosis in digestive system cancer patients. Hh signaling pathway may become a potential therapeutic target in digestive system cancers. PMID- 26835708 TI - Hypermethylation of CpG sites at the promoter region is associated with deregulation of mitochondrial ATPsyn-beta and chemoresistance in acute myeloid leukemia. AB - BACKGROUND: Aberrant DNA methylation status of some genes has been shown to be involved in chemoresistance of acute myeloid leukemia (AML). We have recently found that down-regulation of the beta subunit of mitochondrial ATP synthase (ATPsyn-beta) leads to adriamycin resistance in acute and chronic myeloid leukemia cells, and hypermethylation of the ATPsyn-beta gene promoter is associated with chemoresistance in chronic myeloid leukemia. OBJECTIVE: To further investigate the relationship between methylation of ATPsyn-beta gene, mRNA expression as well as chemoresistance in AML. METHODS: Quantitative RT-PCR and methylation specific PCR were performed to assess mRNA expression and methylation status of ATPsyn-beta gene on primary bone marrow nuclear cells (BMMCs), and cell proliferation assay was used to determine the sensitivity of BMMCs to adriamycin. RESULTS: Hypermethylation status of ATPsyn-beta gene promoter existed in those relapsed/refractory AML patients, and this hypermethylation of the gene was associated with a suppressed mRNA expression levels. Four patients at diagnosis and relapse underwent gene methylation status shift from hypermethylation to hypomethylation, which was accompanied by reduced mRNA expression of the gene. 5-azacitidine(5-Aza)- a demethylating agent, could restore ATPsyn-beta mRNA expression and increase the adriamycin sensitivity of primary leukemic cells from seven relapsed/ refractory AML patients. CONCLUSIONS: Hypermethylation of ATPsyn-beta gene promoter is associated with a down-regulated mRNA expression and chemoresistance in AML patients. PMID- 26835709 TI - High BMI and low HDL-C predict the chemotherapy-related hepatic dysfunction in Chinese advanced NSCLC patients. AB - BACKGROUND: Chemotherapy-related hepatic dysfunction affected the prognosis of non-small cell lung cancer (NSCLC). However, predictive factors of chemotherapy related hepatic dysfunction remained undefined. OBJECTIVE: To identify the predictive factors for hepatic dysfunction during cytotoxic chemotherapy in Chinese patients with advanced NSCLC. METHODS: We retrospectively reviewed the medical records of patients with advanced NSCLC who received cytotoxic chemotherapy at Division of Respiratory Medicine, the affiliated Drum Tower Hospital of Nanjing University, from July 2012 to January 2015. We investigated the incidence of hepatic dysfunction during chemotherapy and evaluated several clinical factors that are associated with hepatic dysfunction, including body mass index (BMI) and high density lipoprotein cholesterol (HDL-C). RESULTS: A total of 116 patients were enrolled in study, 54 patients (46.57%) experienced hepatic dysfunction after receiving chemotherapy. Multivariate analysis for hepatic dysfunction in patients with advanced NSCLC showed that hepatic dysfunction was associated with higher BMI (odds ratio = 4.742, P = 0.001) and lower HDL-C (odds ratio = 3.018, P = 0.019). Pearson's rank correlation analysis revealed that HDL-C and BMI presented a negative correlation in patients with hepatic dysfunction (r = -0.487, P < 0.001). CONCLUSIONS: Higher BMI and lower HDL-C levels seem to be good independent predictive factors for chemotherapy related hepatic dysfunction in advanced NSCLC. In addition, a negative correlation was presented between BMI and HDL-C. PMID- 26835710 TI - miR-146a and miR-638 in BRCA1-deficient triple negative breast cancer tumors, as potential biomarkers for improved overall survival. AB - BACKGROUND: Mechanisms that lead to the reduced expression of BRCA1 in triple negative breast cancer (TNBC) tumors are not fully understood. A possible cause is overexpression of miR-146a and miR-638, which regulate BRCA1 expression in other cancers. OBJECTIVE: To evaluate the expression of these microRNAs in relation to BRCA1 expression in TNBC tumors. METHODS: Expression of both microRNAs was assessed by real time qPCR using Taqman microRNA assays in TNBC tumors. Results were related to protein expression of BRCA1 and patient's survival. RESULTS: miR-146a and miR-638 were overexpressed in 36% and 59% of TNBC tumors, respectively. Overexpression was preeminent in BRCA1-deficient tumors and significantly associated to a better overall survival. CONCLUSION: Both miRNAs are potential biomarkers for improved overall survival in patients with BRCA1 deficient TNBC tumors. PMID- 26835711 TI - The functional 4-bp insertion/deletion ATTG polymorphism in the promoter region of NF-KB1 reduces the risk of BC. AB - Nuclear factor kappaB (NF-kB) plays a key role in mammary gland development and breast cancer (BC) progression. A functional -94 insertion/deletion ATTG polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to affect NF-KB1 expression and confer susceptibility to different types of cancer. The current study aimed to assess the association of NFKB1 -94 insertion/deletion ATTG promoter polymorphism and BC risk in an Iranian population. A total of 439 subjects including on 236 BC patients and 203 healthy women were recruited. The NF-KB1 -94ins/del ATTG polymorphism was genotyped by Allele-Specific polymerase chain reaction (AS-PCR) method. Our results demonstrated that the NF-KB1 94ins/del ATTG polymorphism was associated with a reduced risk of BC in Codominant (Ins/Ins vs. Del/Del: OR = 0.33, 95%CI = 0.17-0.64; P= 0.001), dominant (Ins/Ins vs. Ins/Del+Del/Del: OR = 0.64, 95%CI = 0.42-0.97; P= 0.027) and recessive (Ins/Del+Del/Del vs. Del/Del: OR = 0.40, 95%CI = 0.21-0.75; P= 0.002) tested inheritance models. Additionally, the Del allele of NF-KB1 94ins/del ATTG variation with a higher prevalence in the control group compared to the BC patients (43.3% vs. 33.5%) was associated with a decreased risk of BC (OR = 0.66, 95%CI = 0.50-0.86, P= 0.003). In conclusion, our findings for the first time, suggest that the NF-KB1 -94ins/del Del allele and Del/Del genotype were associated with a reduced risk of BC which may contribute as protective factors against BC. PMID- 26835712 TI - High plasma sST2 levels in gastric cancer and their association with metastatic disease. AB - BACKGROUND: Gastric cancer (GC) is one of the most common and devastating tumor conditions. Its development is closely linked to an infection with Helicobacter pylori and chronic, cytokine-driven inflammation. The proinflammatory cytokine Interleukin-33 (IL-33), its membrane bound cellular receptor ST2L and its soluble receptor sST2 have recently been identified as important factors in various tumor conditions, but their role in GC remains ill-defined. METHODS: Thirty patients with adenocarcinoma of the stomach or the esophagogastric junction were prospectively enrolled in the current study. 51 patients with Helicobacter pylori positive or negative gastritis and 40 healthy volunteers served as control group. Levels of IL-33 and sST2 were determined by ELISA and their relation to HP status, tumor stage and survival was assessed. RESULTS: Soluble ST2 levels in GC were significantly higher than in gastritis or healthy controls (p< 0.0001). Furthermore, higher levels of sST2 were seen in patients with lower degree of tumor differentiation. Soluble ST2 was significantly associated with a more advanced tumor stage (p= 0.018), metastatic disease (p= 0.014) and significantly correlated with the duration of the disease (p= 0.0017). Calculating the ratio of IL-33/sST2 allowed the discrimination of tumor and non-tumor patients. CONCLUSION: Soluble ST2 is associated with advanced and metastatic disease in GC patients and significantly correlates with the duration of the disease. The IL 33/sST2 ratio may offer a new, interesting approach in identifying GC patients. PMID- 26835713 TI - Overexpression of AKR1B10 in nasopharyngeal carcinoma as a potential biomarker. AB - BACKGROUND: Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Southern China. Aldo-keto reductase 1B10 (AKR1B10) is upregulated in multiple tumors and plays an oncogenic role. OBJECTIVE: To examine the expression of AKR1B10 at mRNA and protein levels in nasopharyngeal tumors and correlate its expression with clinicopathological parameters. METHODS: A tissue microarray, paraffin blocks, and frozen surgical nasopharyngeal samples were procured. Western blot and immunohistochemistry were used to estimate AKR1B10 protein expression, and mRNA levels were detected by real time RT-PCR. RESULTS: We found that AKR1B10 expression was increased in malignant tissues compared to the normal tissues (p= 0.000). In NPC tissues, AKR1B10 expression appeared high specifically in squamous cell carcinoma, but low in basal cell carcinoma, adenoid cystic carcinoma, adenocarcinoma and undifferentiated carcinoma (p= 0.000). AKR1B10 expression also demonstrated correlation with tumor differentiation, with a high level in well and moderately differentiated but a low level in poorly differentiated carcinoma (p= 0.000). AKR1B10 was also upregulated in hyperplasia and benign tumors (p= 0.000), and demonstrated a specific nuclear distribution in these non-cancerous diseases. CONCLUSIONS: AKR1B10 is overexpressed in nasopharyngeal hyperplasia, benign tumors, and carcinomas, being a potential new biomarker. PMID- 26835714 TI - Knockdown of USP39 by lentivirus-mediated RNA interference suppresses the growth of oral squamous cell carcinoma. AB - BACKGROUND: Oral squamous cell carcinoma (OSCC) is a frequently diagnosed life threatening oral cancer worldwide and has become one of the leading causes of cancer-related mortality. However, the pathogenesis of this disease is very limited. OBJECTIVE: In this study, we aimed to investigate the functional relationship between OSCC and a potential tumor related gene ubiquitin-specific proteases 39 (USP39). METHODS: The lentivirus-based RNA interference was utilized to knock down USP39 expression in human OSCC CAL27 cells. The effect of USP39 on cell proliferation was detected by MTT and colony formation assays. RESULTS: The results uncovered that the proliferation rate was significantly decreased in specific USP39-targeting lentivirus infected cells compared to control lentivirus infected cells. The colony formation capacity was also attenuated in CAL27 cells after USP39 knockdown. Moreover, knockdown of USP39 arrested CAL27 cells in S and G1/M phases of the cell cycle. Furthermore, USP39 silencing induced apoptosis of CAL27 cells via activations of Caspase 3 and PARP. CONCLUSIONS: In conclusion, the inhibition of USP39 in CAL27 cells suppressed cell growth probably via induction cell cycle arrest and apoptosis. USP39 might act as an oncogenic factor in OSCC and could be a potential molecular target for OSCC gene therapy. PMID- 26835716 TI - Rapid Topochemical Modification of Layered Perovskites via Microwave Reactions. AB - An effective microwave approach to the topochemical modification of different layered oxide perovskite hosts is presented where cation exchange, grafting, and intercalation reactions with acid, n-alkyl alcohols, and n-alkylamines, respectively, are successfully carried out. Microwave-assisted proton exchange reactions involving double- and triple-layered Dion-Jacobson and Ruddlesden Popper perovskite family members, RbLnNb2O7 (Ln = La, Pr), KCa2Nb3O10, Li2CaTa2O7, and Na2La2Ti3O10, were found to be quite efficient, decreasing reaction times from several days to <=3 h. Grafting and intercalation reactions involving double-layered perovskites were also quite rapid with full conversions occurring in as fast as an hour. Interestingly, triple-layered hosts were found to show different behavior; when complete intercalations were possible, grafting reactions were limited at best. Utilization of this rapid synthetic approach could help facilitate the fabrication of new organic-inorganic hybrids. PMID- 26835715 TI - Tumor Selective Silencing Using an RNAi-Conjugated Polymeric Nanopharmaceutical. AB - Small interfering RNA (siRNA) therapeutics have potential advantages over traditional small molecule drugs such as high specificity and the ability to inhibit otherwise "undruggable" targets. However, siRNAs have short plasma half lives in vivo, can induce a cytokine response, and show poor cellular uptake. Formulating siRNA into nanoparticles offers two advantages: enhanced siRNA stability against nuclease degradation beyond what chemical modification alone can provide; and improved site-specific delivery that takes advantage of the enhanced permeability and retention (EPR) effect. Existing delivery systems generally suffer from poor delivery to tumors. Here we describe the formation and biological activity of polymeric nanopharmaceuticals (PNPs) based on biocompatible and biodegradable poly(lactic-co-glycolic acid) (PLGA) conjugated to siRNA via an intracellular cleavable disulfide linker (PLGA-siRNA). Additionally, these PNPs contain (1) PLGA conjugated to polyethylene glycol (PEG) for enhanced pharmacokinetics of the nanocarrier; (2) a cation for complexation of siRNA and charge compensation to avoid high negative zeta potential; and (3) neutral poly(vinyl alcohol) (PVA) to stabilize the PNPs and support the PEG shell to prevent particle aggregation and protein adsorption. The biological data demonstrate that these PNPs achieve prolonged circulation, tumor accumulation that is uniform throughout the tumor, and prolonged tumor-specific knockdown. PNPs employed in this study had no effect on body weight, blood cell count, serum chemistry, or cytokine response at doses >10 times the effective dose. PNPs, therefore, constitute a promising solution for achieving durable siRNA delivery and gene silencing in tumors. PMID- 26835717 TI - Bronsted Acid Catalyzed Functionalization of Aromatic Alcohols through Nucleophilic Substitution of Hydroxyl Group. AB - The hydroxyl groups of naphthol and tautomerizable phenol derivatives have been substituted by O-, S-, N-, and C-centered nucleophiles under solvent-free reaction conditions. The products are generated in good to excellent yields. para Toluenesulfonic acid exhibits the best catalytic activity compared to other Bronsted acids. Experimental observations suggest that the reaction proceeds through the intermediacy of the keto tautomer of naphthol. Nucleophilic addition to the carbonyl group followed by elimination of water generates the desired product. The present methodology provides access to substituted naphtho[2,1 b]furan derivatives. The products generated using N-centered nucleophiles can be further transformed to important classes of organic molecules such as benzocarbazole and imidazole derivatives. PMID- 26835718 TI - Anti-Selective Asymmetric Nitro-Michael Reaction of Furanones: Diastereocontrol by Catalyst. AB - Catalyst-controlled switching of diastereoselectivity from high syn-selectivity (>98/2 dr, syn) to anti-selectivity (up to 96/4 dr, anti) of the asymmetric nitro Michael reaction of furanones is described. Anti-diastereoselectivity of the nitro-Michael reaction is very rare. With 0.1-5 mol % loadings of an epi-quinine catalyst, the reaction of 5-substituted 2(3H)-furanones with nitroalkenes smoothly proceeded to give the anti-Michael adducts in good yields (up to 95%) with excellent diastereo- and enantioselectivities (up to 96/4 dr, anti; up to 99% ee). DFT calculations support a model that accounts the high anti diastereoselectivity. PMID- 26835719 TI - Influence of Water Content on the beta-Sheet Formation, Thermal Stability, Water Removal, and Mechanical Properties of Silk Materials. AB - Silk, which has excellent mechanical toughness and is lightweight, is used as a structural material in nature, for example, in silkworm cocoons and spider draglines. However, the industrial use of silk as a structural material has garnered little attention. For silk to be used as a structural material, its thermal processability and associated properties must be well understood. Although water molecules influence the glass transition of silk, the effects of water content on the other thermal properties of silks are not well understood. In this study, we prepared Bombyx mori cocoon raw fibers, degummed fibers, and films with different water contents and then investigated the effects of water content on crystallization, degradation, and water removal during thermal processing. Thermal gravimetric analyses of the silk materials showed that water content did not affect the thermal degradation temperature but did influence the water removal behavior. By increasing the water content of silk, the water molecules were removed at lower temperatures, indicating that the amount of free water in silk materials increased; additionally, the glass transition temperature decreased with increasing water plasticization. Differential scanning calorimetry and wide-angle X-ray scattering of the silk films also suggested that the water molecules in the amorphous regions of the silk films acted as a plasticizer and induced beta-sheet crystallization. The plasticizing effect of water was not detected in silk fibers, owing to their lower amorphous content and mobility. The structural and mechanical characterizations of the silk films demonstrated the silk film prepared at RH 97% realized both crystallinity and ductility simultaneously. Thus, the thermal stability, mechanical, and other properties of silk materials are regulated by their water content and crystallinity. PMID- 26835720 TI - Comparison of Bioavailability and Biotransformation of Inorganic and Organic Arsenic to Two Marine Fish. AB - Dietary uptake could be the primary route of arsenic (As) bioaccumulation in marine fish, but the bioavailability of inorganic and organic As remains elusive. In this study, we investigated the trophic transfer and bioavailability of As in herbivorous rabbitfish Siganus fuscescens and carnivorous seabass Lateolabrax japonicus. Rabbitfish were fed with one artificial diet or three macroalgae, whereas seabass were fed with one artificial diet, one polychaete, or two bivalves for 28 days. The six spiked fresh prey diets contained different proportions of inorganic As [As(III) and As(V)] and organic As compounds [methylarsenate (MMA), dimethylarsenate (DMA), and arsenobetaine (AsB)], and the spiked artificial diet mainly contained As(III) or As(V). We demonstrated that the trophic transfer factors (TTF) of As in both fish were negatively correlated with the concentrations of inorganic As in the diets, while there was no relationship between TTF and the AsB concentrations in the diets. Positive correlation was observed between the accumulated As concentrations and the AsB concentrations in both fish, suggesting that organic As compounds (AsB) were more trophically available than inorganic As. Furthermore, the biotransformation ability of seabass was higher than that in rabbitfish, which resulted in higher As accumulation in seabass than in rabbitfish. Our study demonstrated that different prey with different inorganic/organic As proportions resulted in diverse bioaccumulation of total As in different marine fish. PMID- 26835721 TI - Investigation of Reagent Delivery Formats in a Multivalent Malaria Sandwich Immunoassay and Implications for Assay Performance. AB - Conventional lateral flow tests (LFTs), the current standard bioassay format used in low-resource point-of-care (POC) settings, have limitations that have held back their application in the testing of low concentration analytes requiring high sensitivity and low limits of detection. LFTs use a premix format for a rapid one-step delivery of premixed sample and labeled antibody to the detection region. We have compared the signal characteristics of two types of reagent delivery formats in a model system of a sandwich immunoassay for malarial protein detection. The premix format produced a uniform binding profile within the detection region. In contrast, decoupling the delivery of sample and labeled antibody to the detection region in a sequential format produced a nonuniform binding profile in which the majority of the signal was localized to the upstream edge of the detection region. The assay response was characterized in both the sequential and premix formats. The sequential format had a 4- to 10-fold lower limit of detection than the premix format, depending on assay conjugate concentration. A mathematical model of the assay quantitatively reproduced the experimental binding profiles for a set of rate constants that were consistent with surface plasmon resonance measurements and absorbance measurements of the experimental multivalent malaria system. PMID- 26835722 TI - Enhancement of Spanish Oesophageal Speech vowels using coherent subband modulator Kalman filtering. AB - This paper proposes an Oesophageal Speech (OES) enhancement method, based on Kalman filtering. The Kalman filter is applied to modulators of OES frequency subbands instead of the fullband signal. The OES frequency subbands are decomposed into modulators and carriers components using coherent demodulation. In comparison with fullband Kalman filtering and pole stabilization, the proposed technique shows better results. The system performance is evaluated objectively and subjectively using the Harmonic to Noise Ratio (HNR) and Mean Opinion Score (MOS) respectively. Results have shown that Kalman filter in subband modulators processing is robust and efficient, improving the HNR by 4 to 5 dB for all Spanish vowels. PMID- 26835723 TI - An equivalent astable multivibrator model to assess flow instability and dysfunction risk in in-vitro stenotic arteriovenous grafts. AB - Narrowed vessel accesses produce blood flow changes, and induce flow instability and vessel wall vibration, resulting in blood pressure, flow velocity, and flow resistance increases. The vessel wall vibrates and propagates the low axial blood flow, as representing the resistance (R) to blood flow. The compliance is a blood pressure-blood volume relation, representing the systole and diastole capacity of the blood vessel. These dynamic behaviors increase blood flow resistances and reduce blood vessel compliances. Vibration phenomena result on the elastic vessel walls and induce simple harmonic motion due to transverse vibration pressure (TVP). The rise time, amplitude, and pulse duration of transverse waves are determined by the flow resistances (R) and vessel compliances (C). Thus, a stenotic arteriovenous access has high resistance and low compliance, which can be expressed an astable multivibrator as an equivalent model consisting of a lumped resistor (R) and a lumped capacitor (C). TVP's oscillation frequency, rise time, and amplitude are determined by the flow resistances and vessel compliances. Hence, an astable multivibrator is used to model TVP parameters to estimate negative time constants, tau=(R* C), which are used to evaluate the flow instability and the dysfunction risk in in-vitro arteriovenous grafts (AVGs). Experimental results show the average negative time constants have the positive correlation as the degree of stenosis (DOS) increases (R2 = 0.8944), and their variations with the flow resistance and vessel compliance are also validated. Positive pole values, s=(-1/tau), are used to show that the force responses of the vessel walls grow in a finite time, 0.5415 +/- 7.60 * 10-3 sec, and the equivalent model would be also unstable as DOS increases (R2 = 0.8802). By comparison with hemodynamic analysis, the finding of proposed model can be further carried out for screening AVG dysfunction risk during hemodialysis treatment. PMID- 26835725 TI - Experimental and CFD flow studies in an intracranial aneurysm model with Newtonian and non-Newtonian fluids. AB - BACKGROUND: According to the clinical data, flow conditions play a major role in the genesis of intracranial aneurysms. The disorder of the flow structure is the cause of damage of the inner layer of the vessel wall, which leads to the development of cerebral aneurysms. Knowledge of the alteration of the flow field in the aneurysm region is important for treatment. OBJECTIVE: The aim is to study quantitatively the flow structure in an patient-specific aneurysm model of the internal carotid artery using both experimental and computational fluid dynamics (CFD) methods with Newtonian and non-Newtonian fluids. METHODS: A patient specific geometry of aneurysm of the internal carotid artery was used. Patient data was segmented and smoothed to obtain geometrical model. An elastic true-to scale silicone model was created with stereolithography. For initial investigation of the blood flow, the flow was visualized by adding particles into the silicone model. The precise flow velocity measurements were done using 1D Laser Doppler Anemometer with a spatial resolution of 50 MU m and a temporal resolution of 1 ms. The local velocity measurements were done at a distance of 4 mm to each other. A fluid with non-Newtonian properties was used in the experiment. The CFD simulations for unsteady-state problem were done using constructed hexahedral mesh for Newtonian and non-Newtonian fluids. RESULTS: Using 1D laser Doppler Anemometer the minimum velocity magnitude at the end of systole -0.01 m/s was obtained in the aneurysm dome while the maximum velocity 1 m/s was at the center of the outlet segment. On central cross section of the aneurysm the maximum velocity value is only 20% of the average inlet velocity. The average velocity on the cross-section is only 11% of the inlet axial velocity. Using the CFD simulation the wall shear stresses for Newtonian and non Newtonian fluid at the end of systolic phase (t= 0.25 s) were computed. The wall shear stress varies from 3.52 mPa (minimum value) to 10.21 Pa (maximum value) for the Newtonian fluid. For the non-Newtonian fluid the wall shear stress minimum is 2.94 mPa; the maximum is 9.14 Pa. The lowest value of the wall shear stress for both fluids was obtained at the dome of the aneurysm while the highest wall shear stress was at the beginning of the outlet segment. The vortex in the aneurysm region is unstable during the cardiac cycle. The clockwise rotation of the streamlines at the inlet segment for Newtonian and non-Newtonian fluid is shown. CONCLUSION: The results of the present study are in agreement with the hemodynamics theory of aneurysm genesis. Low value of wall shear stress is observed at the aneurysm dome which can cause a rupture of an aneurysm. PMID- 26835724 TI - A pocket-sized hand held ultrasound system for intraoperative transthoracic echocardiography by anaesthesiologists: A feasibility study. AB - BACKGROUND: The intraoperative application of focused transthoracic echocardiography (TTE) is often considered to be restricted. Echocardiography with pocket-sized hand held ultrasound systems has been shown to be feasible in various settings. OBJECTIVE: The aim of this study was to investigate the feasibility of the intraoperative application of pocket-sized echocardiography and the comparison of its imaging quality and diagnostic reliability and variability with a standard ultrasound system. METHODS: After written informed consent, TTE was performed on 40 anaesthetised general, vascular, visceral, thoracic surgical and orthopaedic patients according to the FATE protocol: first, with a pocket-sized and second, with a high-end ultrasound system randomly by two anaesthetists. Imaging quality of four basic and three additional FATE views was rated on an established scale from 1 (impossible) to 5 (perfect). Successful TTE was defined, if one basic FATE views would be rated as grade 4 or 5 or alternatively two views as grade 3. Pathologic findings by both ultrasound devices were documented and imaging quality and pathologic findings were compared. RESULTS: All 40 patients presented acceptable imaging quality, resulting in a success rate of 1.0 (97.5%-CI 0.91-1, p= 0.015). The individual imaging ratings of each view were significantly lower with the pocket-sized system, but still showed acceptable imaging quality. With the high-end device more pathologic findings were detected (107 vs. 87), but none of the relevant or severe pathologies were overseen with the hand-held device. CONCLUSION: The application of a pocket-sized echocardiography device for focused intraoperative TTE is feasible and can appropriate be used for the initial evaluation of relevant pathologies in the operating theatre. PMID- 26835726 TI - Efficient leukocyte segmentation and recognition in peripheral blood image. AB - BACKGROUND: Blood cell count, also known as differential count of various types of blood cells, provides valuable information in order to assess variety of diseases like AIDS, leukemia and blood cancer. Manual techniques are still used in diseases diagnosis that is very lingering and tedious process. However, machine based automatic analysis of leukocyte is a powerful tool that could reduce the human errors, improve the accuracy, and minimize the required time for blood cell analysis. However, leukocyte segmentation is a challenging process due to the complexity of the blood cell image; therefore, this task remains unresolved issue in the blood cell segmentation. OBJECTIVE: The aim of this work is to develop an efficient leukocyte cell segmentation and classification system. METHODS: This paper presents an efficient strategy to segment cell images. This has been achieved by using Wiener filter along with Curvelet transform for image enhancement and noise elimination in order to elude false edges. We have also used combination of entropy filter, thresholding and mathematical morphology for obtaining image segmentation and boundary detection, whereas we have used back propagation neural network for leukocyte classification into its sub classes. RESULTS: As a result, the generated segmentation results are fruitful in a sense that we have overcome the problem of overlapping cells. We have obtained 100%, 96.15%, 92.30%, 92.30% and 96.15% accuracy for basophil, eosinophil, monocyte, lymphocyte and neutrophil respectively. PMID- 26835727 TI - Analysis of cancer-related fatigue based on smart bracelet devices. AB - BACKGROUND: Fatigue is the most common symptom associated with cancer and its treatment, and profoundly affects all aspects of quality of life for cancer patients. It is very important to measure and manage cancer-related fatigue. Usually, the cancer-related fatigue scores, which estimate the degree of fatigue, are self-reported by cancer patients using standardized assessment tools. But most of the classical methods used for measurement of fatigue are subjective and inconvenient. OBJECTIVE: In this study, we try to establish a new method to assess cancer-related fatigue objectively and accurately by using smart bracelet. METHODS: All patients with metastatic pancreatic cancer wore smart bracelet for recording the physical activity including step count and sleep time before and after chemotherapy. Meantime, their psychological state was assessed by completing questionnaire tables as cancer-related fatigue scores. RESULTS: Step count record by smart bracelet reflecting the physical performance dramatically decreased in the initial days of chemotherapy and recovered in the next few days. Statistical analysis showed a strong and significant correlation between self reported cancer-related fatigue and physical performance (P= 0.000, r=-0.929). Sleep time was also significantly correlated with fatigue (P= 0.000, r= 0.723). Multiple regression analysis showed that physical performance and sleep time are significant predictors of fatigue. CONCLUSIONS: Measuring activity using smart bracelets may be an appropriate method for quantitative and objective measurement of cancer-related fatigue by using smart bracelet devices. PMID- 26835728 TI - Effect of elasticity on wall shear stress inside cerebral aneurysm at anterior cerebral artery. AB - BACKGROUND: Many numerical studies have been published with respect to about flow structures around cerebral aneurysm assuming to be rigid. Furthermore, there is little experimental research concerning aneurysm with elastic wall. Wall shear stress in elastic wall comparing with rigid wall should be clarified in experimental approach and verified in CFD. OBJECTIVE: We have experimentally realized elastic aneurysm model accompanying with wall deformation. Wall shear stress was examined for both rigid and elastic aneurysm models in pulsatile flow. METHODS: Effect of elasticity on wall shear stress inside aneurysm induced at the apex of anterior cerebral artery was experimentally examined by particle image velocimetry in vitro. In order to adjust the wall deformation, the pressure adjustment chamber was specially equipped outside the aneurysm wall. RESULTS: Effect of elasticity on wall shear stress was noticed on the comparison with that of rigidity. Wall elasticity reduced the peak magnitude, the spatial and temporal averaged wall shear stress comparing with those of wall rigidity experimentally. These reductions were endorsed by fluid-structure interaction simulation. CONCLUSION: Elastic wall comparing with rigid wall would reduce the peak magnitude, the spatial and temporal averaged wall shear stress acting on vascular wall. PMID- 26835729 TI - A comparison study on the design of mirror and anatomy reconstruction technique in maxillofacial region. AB - BACKGROUND: The customized mandible reconstruction has been a challenging task in maxillofacial surgery. Designing an implant taking into considering the surrounding bone contours is really critical. Various computer aided design techniques have been used in the designing the customized reconstruction implants, but nevertheless study on the comparison between these techniques is rarely used. OBJECTIVE: The objective of this study is to compare the mirroring and anatomical reconstruction design techniques used in the maxillofacial surgery and select the best design technique. METHODS: The three mandible bone defects small (< 20 mm), medium (20 to 40 mm) and large (41 to 53 mm) tumors are reconstructed using the two reconstruction design techniques and compared to their accuracy, using a 3 dimensional (3D) implant design evaluation and part to Computer aided design (CAD) comparison using a Co-ordinate measuring machine (CMM). RESULTS: The analysis results indicate that the mirroring technique provides higher accuracy for the implant design as compared to the anatomical technique for the medium and large tumors at maxillofacial regions. In case of implant design in small tumors, the anatomical design provides perfect implant fitting. CONCLUSIONS: Based on the results, it is recommended to select the anatomy design technique only for small tumor regions and mirroring technique for medium and large tumors. PMID- 26835730 TI - Noninvasive tongue-motion controlled computer mouse for the disabled. AB - BACKGROUND: A patient whose spinal cord was damaged due to accident may result in Tetraplegia or lose the ability to control his/her daily living environment. Currently, patients must use an invasive tool tongue movement, to help the patient communicate with the external environment. OBJECTIVE: This study designed a non-invasive tongue movement computer mouse system that allows the patient to use tongue movement to control a computer to communicate with the external environment. METHODS: Via a pressure sensor and assistive holder designed in this study, the pressure sensor can be moved using the assistive holder close to the mylohyoid muscle of the patient's lower jaw. The changes in pressure from the mylohyoid muscle are converted into computer mouse control signals to control a computer to communicate with the external environment. RESULTS: This study is based on ISO9241-Part 9 to design four kinds of training modes with varying difficulties. The data were collected from five able persons participating in the test over 7 days. The data includes throughput, path efficiency, test completion time and reaction time. The data verifies that the proposed system is stable and practical for persons with disabilities. CONCLUSION: The non-invasive computer mouse system for sensing tongue movement can completely breakthrough the limitations of the invasive tongue movement sensing system. This study uses non invasive, simple tongue movements that correspond to the stretching and shrinking of the lower jaw mylohyoid muscle to control the computer mouse. PMID- 26835731 TI - The angle-torque-relationship of the subtalar pronators and supinators in male athletes: A comparative study of soccer and handball players. AB - BACKGROUND: It is currently unclear how participation in different sports affects the angle-specific subtalar pronator and supinator muscle strength and pronator to-supinator strength ratio (PSR). OBJECTIVE: Based on the hypothesis that both differences sport-related patterns of play and foot-ground interaction may lead to sport-specific muscle adaptations, this study compared the angle specific pronator and supinator strength capacity of handball and soccer players. METHODS: Eighteen healthy male handball and 19 soccer players performed maximum isometric voluntary isometric contractions using a custom-made testing apparatus. Peak pronator (PPT) and supinator torques (PST), pronator and supinator strength curves (normalised to the peak torque across all joint angles) and PSR were measured in five anatomical joint angles across the active subtalar range of motion (ROM). RESULTS: All analysed parameters were dependent on the subtalar joint angle. The ANOVA revealed significant 'joint angle' * 'group' interactions on PPT, pronator strength curves and PSR. No group differences were found for active subtalar ROM. CONCLUSION: In previously uninjured handball and soccer athletes, there were intrinsic differences in angle-specific subtalar pronator muscle strength. The lower PSR, which was found in the most supinated angle, can be seen as a risk factor for sustaining an ankle sprain. PMID- 26835732 TI - Non-operative treatment of lumbar spinal stenosis. AB - BACKGROUND AND OBJECTIVE: Non-operative treatment is widely accepted for early stages of lumbar spinal stenosis. In general, a trial of conservative treatment is recommended prior to surgery. However, there is an ongoing debate regarding benefits from non-operative treatment and their duration. METHODS: Thirty-eight patients were included in this prospective study. All patients received repeated epidural injections and facet joint injections as well as physiotherapy during a one week hospitalization. Patient characteristics, VAS scores, COMI and ODI scores and SF-36 were assessed prior to and immediately after treatment as well as after six, twelve, and 26 weeks. For six weeks after treatment, patients were asked to record a pain diary. RESULTS: Back and leg pain scores improved significantly on VAS up to three months follow-up. COMI score improved significantly over the entire follow-up. Regarding quality of life, mental sub scores showed no improvement. Physical component summary scores improved for the first three months. CONCLUSIONS: Non-operative treatment offers pain relief and improves physical function for three months. COMI scores improve up to six months follow-up. Spine Tango registry offers standardized instruments for outcome evaluation of non-operative treatment. PMID- 26835733 TI - LEGO Mindstorms NXT for elderly and visually impaired people in need: A platform. AB - This paper presents the employment of LEGO Mindstorms NXT robotics as core component of low cost multidisciplinary platform for assisting elderly and visually impaired people. LEGO Mindstorms system offers a plug-and-play programmable robotics toolkit, incorporating construction guides, microcontrollers and sensors, all connected via a comprehensive programming language. It facilitates, without special training and at low cost, the use of such device for interpersonal communication and for handling multiple tasks required for elderly and visually impaired people in-need. The research project provides a model for larger-scale implementation, tackling the issues of creating additional functions in order to assist people in-need. The new functions were built and programmed using MATLAB through a user friendly Graphical User Interface (GUI). Power consumption problem, besides the integration of WiFi connection has been resolved, incorporating GPS application on smart phones enhanced the guiding and tracking functions. We believe that developing and expanding the system to encompass a range of applications beyond the initial design schematics to ease conducting a limited number of pre-described protocols. However, the beneficiaries for the proposed research would be limited to elderly people who require assistance within their household as assistive-robot to facilitate a low-cost solution for a highly demanding health circumstance. PMID- 26835734 TI - Immunogenicity of Recombinant Human Interferon Beta-1b in Immune-Tolerant Transgenic Mice Corresponds with the Biophysical Characteristics of Aggregates. AB - Determining to what extent biophysical characteristics of aggregates affect immunogenicity of therapeutic interferon beta-1b. Three recombinant human interferon beta-1b (rhIFNbeta-1b) samples with different levels of aggregates generated by copper oxidation, thermal stress, or left untreated, as well as Avonex((r)) drug substance and Betaferon((r)) drug product, were injected intraperitoneally in nontransgenic and interferon beta transgenic FVB/N mice 5 times per week for 3 weeks. Antibodies against interferon beta were measured using enzyme-linked immunosorbent assay. UV and fluorescence spectroscopy, dynamic light scattering, size exclusion chromatography, reversed-phase high performance liquid chromatography (RP-HPLC), fluid imaging microscopy, and resonant mass measurement, as well as sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting, were used to characterize and quantitate aggregates in the 3 rhIFNbeta preparations, to correlate biophysical characteristics with immunogenicity. In immune-tolerant interferon beta transgenic FVB/N mice, Betaferon drug product showed the highest immunogenicity, while Avonex drug substance showed the lowest level of immunogenicity. Of the 3 forms of rhIFNbeta-1b, copper-oxidized rhIFNbeta-1b showed lower immunogenicity than thermally stressed rhIFNbeta-1b, despite containing larger aggregates. Both copper-oxidized rhIFNbeta-1b and thermally stressed rhIFNbeta-1b exhibited changes in protein structure as shown using fluorescence spectroscopy and RP HPLC. Nontransgenic, nonimmune-tolerant FVB/N mice generated high antibody titers against all interferon beta samples tested. The level of immunogenicity and the breaking of tolerance in FVB/N transgenic mice are not only related to the level of aggregation but also depend on the size and structure of the aggregates. PMID- 26835735 TI - 'I won't be able to go home being pregnant': sex work and pregnancy in Dhaka, Bangladesh. AB - Sex workers report high rates of unintended pregnancy that are inconsistent with widespread reports of condom use. Greater understanding of the implications of an unintended pregnancy and barriers to contraceptive use is needed to better meet the broader sexual and reproductive health needs of this population. We conducted in-depth interviews with 20 women sex workers in Dhaka, Bangladesh. Findings reveal that most women are trying to conform to societal norms and protect their reputations. They fear pregnancy would reveal that they are having unsanctioned sex and that they are sex workers. This could lead to ostracism from families and society, resulting in homelessness and abandonment by partners. Pregnancy may affect a sex worker's ability to work and leave her unable to meet financial obligations. All study participants were using condoms but most acknowledged they could not use them consistently. They had all tried other contraceptive methods, notably injectables and the pill, but some noted experience of side-effects, difficulties in adherence and the desire to use other methods. Understanding the context of sex workers' lives is an important step in informing stakeholders about the range of services needed to improve their sexual and reproductive health. PMID- 26835736 TI - The New Normal of Military Orthopaedic and Rehabilitative Care. PMID- 26835737 TI - Raising Awareness of the Value of Orthotic and Prosthetic Care. PMID- 26835738 TI - Proceedings of the AMSUS Summit for Federal and Civilian Orthopedic Rehabilitation Programs. PMID- 26835739 TI - Suggested Guidelines for the Prescription of Orthotic Services, Device Delivery, Education, and Follow-up Care: A Multidisciplinary White Paper. AB - OBJECTIVES: This article establishes needed guidelines for determining orthotic prescriber authority, documenting medical necessity, and ensuring continuity of care for patients needing orthoses. It also identifies "off-the-shelf" (OTS) devices that can safely and appropriately be delivered to patients without professional adjustment as well as those that cannot. METHODS: A multidisciplinary task force made up of experts in orthopedics and physical medicine physicians, along with therapists and certified orthotists, applied a consensus approach to answer key questions: (i) When can a device be safely, effectively delivered to the patient OTS without professional guidance or education, and which caregivers have a role in that decision? (ii) What documentation is appropriate for physicians and other caregivers to determine medical necessity? (iii) What documentation/communication ensures continuity of care among physicians, therapists, and orthotists? RESULTS: Guidelines developed for consideration of OTS orthoses include accepting documentation from collaborating caregivers, including therapists and orthotists; keeping that documentation as part of the patient's total medical record for clinical, medical necessity determinations and reimbursement purposes; and using the physician's prescription for the device as the key determinant of whether a device is delivered OTS or as a custom-fitted device. CONCLUSION: This review provides expert guidance for patient safety, minimizing wasted expenditures, maximizing clinical outcomes, and providing efficient delivery of care for Medicare and other patients. Centers for Medicare and Medicaid Services guidelines should be directed toward recognizing the level of expertise of the orthotist, the value of their patient encounters, and their role in facilitating the timely, safe, and effective use of orthotic devices. PMID- 26835740 TI - Economic Value of Prosthetic Services Among Medicare Beneficiaries: A Claims Based Retrospective Cohort Study. AB - CONTEXT: There are few studies of the economic impact or value of lower extremity prosthetic services. Results from this study can inform the value proposition concerning prosthetic services within military health, where over 40,000 Veterans with limb-loss receive care for their amputations through the Veterans Administration health care system. PURPOSE: To determine the extent to which Medicare patients who received selected prosthetic services had less health care utilization, lower Medicare payments, and/or fewer negative outcomes compared to matched patients not receiving these services. METHODS: This retrospective cohort analysis using Medicare claims data (2007-2010) and propensity score matching techniques to control for observable selection bias based on etiological diagnosis, comorbidities, patient characteristics, and historical health care utilization one year before the etiological diagnosis. FINDINGS: Patients who received lower extremity prostheses had comparable Medicare episode payments ($6,099 per-member-per-month for study group, $6,015 per-member-per-month for comparison group) and better outcomes than patients who did not receive prostheses. Study group patients were more likely to receive extensive outpatient therapy than comparison group patients (p < 0.05). Receiving physical therapy is associated with fewer hospitalizations and emergency room visits, and less facility-based care (p < 0.05), essentially offsetting the cost of the prosthetic over a 12-month time frame. PMID- 26835741 TI - Improvement of kidney redox states contributes to the beneficial effects of dietary pomegranate peel against barium chloride-induced nephrotoxicity in adult rats. AB - CONTEXT: Pomegranate (Punica granatum L., Punicaceae) is known to possess enormous antioxidant activity. OBJECTIVE: This study investigates the protective effects of pomegranate peel against barium-mediated renal damage. MATERIALS AND METHODS: Rats were exposed during 21 days either to barium (67 ppm), barium + pomegranate peel (5% of diet) or to only pomegranate peel (5% of diet). RESULTS: Exposure rats to barium provoked a significant increase in kidney malondialdehyde (MDA), advanced oxidation protein products (AOPP) and hydrogen peroxide (H2O2) levels. Creatinine, urea and uric acid levels in plasma and urine were also modified. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, non protein thiol (NPSH) and reduced glutathione (GSH) levels were decreased. Metallothionein (MT) production was increased and their genes expressions were up-regulated. All these changes were improved by dietary pomegranate peel. Moreover, the distorted histoarchitecture in kidney of barium group was alleviated by pomegranate peel. CONCLUSION: Our data showed, for the first time, the protective effects of pomegranate peel against barium-induced renal oxidative damage. PMID- 26835743 TI - Adherence to Adjuvant Neuropathic Pain Medications in a Palliative Care Clinic. AB - BACKGROUND: Currently, few studies exist on patient adherence to adjuvant neuropathic pain (NP) medications in the palliative care setting. OBJECTIVES: We assessed patient adherence rates to NP medications in a palliative care clinic and compared patient self-reported adherence to pharmacy refill records. METHODS: This was an observational single-site cross-sectional study of patients with NP receiving at least one NP medication for at least three months. Participants who met the inclusion criteria and agreed to participate completed the eight-item Morisky Medication Adherence Scale (MMAS-8) and a seven-day-recall (7DR) adherence measure. Patients gave permission to contact their pharmacy after the visit to collect refill records for the six months prior to the clinic visit. This information was used to calculate the medication possession ratio (MPR). RESULTS: We analyzed 32 patients; most (81%) had NP related to a cancer diagnosis. Approximately 87.5% had low or medium adherence using the MMAS-8. The mean self-reported adherence based on 7DR was 94%. The mean MPR was 63%. A majority of patients (88%) had high self-reported adherence (>80%); however only 44% of patients had an MPR >80%. CONCLUSION: Results indicated that the MPR might be a more accurate measure of adherence than patient self-report. More research is needed to assess and improve adherence with NP medications in the outpatient palliative care setting. PMID- 26835742 TI - GnRH Pulse Frequency Control of Fshb Gene Expression Is Mediated via ERK1/2 Regulation of ICER. AB - The pulsatile release of GnRH regulates the synthesis and secretion of pituitary FSH and LH. Two transcription factors, cAMP-response element-binding protein (CREB) and inducible cAMP early repressor (ICER), have been implicated in the regulation of rat Fshb gene expression. We previously showed that the protein kinase A pathway mediates GnRH-stimulated CREB activation. We hypothesized that CREB and ICER are activated by distinct signaling pathways in response to pulsatile GnRH to modulate Fshb gene expression, which is preferentially stimulated at low vs high pulse frequencies. In the LbetaT2 gonadotrope-derived cell line, GnRH stimulation increased ICER mRNA and protein. Blockade of ERK activation with mitogen-activated protein kinase kinase I/II (MEKI/II) inhibitors significantly attenuated GnRH induction of ICER mRNA and protein, whereas protein kinase C, calcium/calmodulin-dependent protein kinase II, and protein kinase A inhibitors had minimal effects. GnRH also stimulated ICER in primary mouse pituitary cultures, attenuated similarly by a MEKI/II inhibitor. In a perifusion paradigm, MEKI/II inhibition in LbetaT2 cells stimulated with pulsatile GnRH abrogated ICER induction at high GnRH pulse frequencies, with minimal effect at low frequencies. MEKI/II inhibition reduced GnRH stimulation of Fshb at high and low pulse frequencies, suggesting that the ERK pathway has additional effects on GnRH regulation of Fshb, beyond those mediated by ICER. Indeed, induction of the activating protein 1 proteins, cFos and cJun, positive modulators of Fshb transcription, by pulsatile GnRH was also abrogated by inhibition of the MEK/ERK signaling pathway. Collectively, these studies indicate that the signaling pathways mediating GnRH activation of CREB and ICER are distinct, contributing to the decoding of the pulsatile GnRH to regulate FSHbeta expression. PMID- 26835745 TI - Chromosomal mapping of H3 histone and 5S rRNA genes in eight species of Astyanax (Pisces, Characiformes) with different diploid numbers: syntenic conservation of repetitive genes. AB - The genus Astyanax is widely distributed from the southern United States to northern Patagonia, Argentina. While cytogenetic studies have been performed for this genus, little is known about the histone gene families. The aim of this study was to examine the chromosomal relationships among the different species of Astyanax. The chromosomal locations of the 5S rRNA and H3 histone genes were determined in A. abramis, A. asuncionensis, A. altiparanae, A. bockmanni, A. eigenmanniorum, A. mexicanus (all 2n = 50), A. fasciatus (2n = 46), and A. schubarti (2n = 36). All eight species exhibited H3 histone clusters on two chromosome pairs. In six species (A. abramis, A. asuncionensis, A. altiparanae, A. bockmanni, A. eigenmanniorum, and A. fasciatus), syntenic clusters of H3 histone and 5S rDNA were observed on metacentric (m) or submetacentric (sm) chromosomes. In seven species, clusters of 5S rDNA sequences were located on one or two chromosome pairs. In A. mexicanus, 5S rDNA clusters were located on four chromosome pairs. This study demonstrates that H3 histone clusters are conserved on two chromosome pairs in the genus Astyanax, and specific chromosomal features may contribute to the genomic organization of the H3 histone and 5S rRNA genes. PMID- 26835744 TI - Impact of Irritability and Impulsive Aggressive Behavior on Impairment and Social Functioning in Youth with Cyclothymic Disorder. AB - OBJECTIVE: Research on adults with cyclothymic disorder (CycD) suggests that irritability and impulsive aggression (IA) are highly prevalent among this population. Less is known about whether these behaviors might also distinguish youth with CycD from youth without CycD. Additionally, little is known about how irritability and IA relate to one another, and whether they are associated with different outcomes. This study aimed to compare irritability and IA across diagnostic subtypes to determine whether CycD is uniquely associated with these behaviors, and to assess how irritability and IA relate to youth social and general functioning. METHODS: Participants (n = 459), 11-18 years of age, were recruited from an urban community mental health center and an academic outpatient clinic; 25 had a diagnosis of CycD. Youth and caregivers completed measures of IA and irritability. Youth and caregivers also completed an assessment of youth friendship quality. Clinical interviewers assessed youth social, family, and school functioning. RESULTS: Youth with CycD had higher scores on measures of irritability and IA than youth with nonbipolar disorders, but scores were not different from other youth with bipolar spectrum disorders. Measures of irritability and IA were correlated, but represented distinct constructs. Regression analyses indicated that irritability was related to friendship quality (p < 0.005). Both IA and irritability were related to social impairment (ps < 0.05-0.0005) and Child Global Assessment Scale (C-GAS) scores (ps = 0.05-0.005). CycD diagnosis was associated with poorer caregiver-rated friendship quality and social functioning (ps < 0.05). CONCLUSIONS: We found that irritability and aggression were more severe among youth with CycD than among youth with nonbipolar diagnoses, but did not differ across bipolar disorder subtypes. Among youth seeking treatment for mental illness, irritability and IA are prevalent and nonspecific. Irritability and IA were uniquely related to our outcomes of social and general functioning, suggesting that it is worthwhile to assess each separately, in order to broaden our understanding of the characteristics and correlates of each. PMID- 26835747 TI - Reliability of reports of childhood trauma in bipolar disorder: A test-retest study over 18 months. AB - This study aimed to explore the reliability of self-reported trauma histories in a population with a diagnosis of bipolar disorder using the Childhood Trauma Questionnaire. Previous studies in other populations suggest high reliability of trauma histories over time, and it was postulated that a similar high reliability would be demonstrated in this population. A total of 39 patients with a confirmed diagnosis (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria) were followed up and readministered the Childhood Trauma Questionnaire after 18 months. Cohen's kappa scores and intraclass correlations suggested reasonable test-retest reliability over the 18-month time period of the study for all types of childhood abuse, namely, emotional, physical, and sexual abuse and physical and emotional neglect. Intraclass correlations ranged from r = .50 (sexual abuse) to r = .96 (physical abuse). Cohen's kappas ranged from .44 (sexual abuse) to .76 (physical abuse). Retrospective reports of childhood trauma can be seen as reliable and are in keeping with results found with other mental health populations. PMID- 26835748 TI - Neutrophil to Lymphocyte and Platelet to Lymphocyte Ratios Are More Effective than the Fournier's Gangrene Severity Index for Predicting Poor Prognosis in Fournier's Gangrene. AB - BACKGROUND: We investigated the value of the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) as markers of mortality in patients with Fournier's gangrene. METHODS: Records from 62 patients treated for Fournier's gangrene between 2003 and 2014 were reviewed retrospectively. Data were collected regarding medical history, symptoms, physical examination findings, admission laboratory tests, and the extent of body surface area involved (%). Fournier's Gangrene Severity Index score, NLR, and PLR were calculated. The data were assessed separately for surviving and deceased patients. RESULTS: Of the 62 patients, 36 survived (58%, group 1) and 26 died (42%, group 2). Parameters that were statistically different between the two groups (p < 0.05) were the NLR, PLR, Fournier's Gangrene Severity Index score, and admission laboratory parameters, including body temperature, heart rate, bicarbonate, albumin, and serum calcium. The average body surface area affected in group 2 was statistically different from that of group 1 (6.0% versus 2.3%, p = 0.001). A high Fournier's Gangrene Severity Index score (>9), high NLR (>8), and high PLR (>140) were associated more frequently with group 2 patients. Multivariable regression analysis showed that high NLR (adjusted odds ratio [OR], 4.66; 95% confidence interval [CI], 1.25 17.3; p = 0.022) and high PLR (adjusted OR, 11.6; 95% CI, 2.7-49.5; p = 0.001) were independent prognostic factors for poor prognosis from Fournier's gangrene. However, the Fournier's Gangrene Severity Index score did not shown any statistically significant effect on mortality (p = 0.086). CONCLUSIONS: The Fournier's Gangrene Severity Index scoring system was not associated with determining poor prognosis, however, high NLR and high PLR were associated with predictors of mortality in patients with Fournier's gangrene. PMID- 26835749 TI - Fellows as Teachers: Raising the Educational Bar. AB - Fellows are expected to educate trainees, peers, and patients, during and long after fellowship. However, there has been relatively little emphasis on the acquisition of teaching skills in fellowship programs. Challenges to teaching by fellows during subspecialty training include demanding clinical duties, their limited knowledge base in the field, brief contact time with learners during consultative roles, and, for new fellows, personal unfamiliarity with the learners and hospital culture. Fellows' teaching skills can be improved by formal curricula addressing teaching, and by direct observation and feedback of teaching akin to what is provided for learning clinical care. Further expansion of fellow as-teacher programs will allow in-depth training for fellows seeking careers as medical educators. Even without such dedicated programs, emphasis on honing teaching skills during fellowship will telegraph the importance of teaching and help evolve divisional culture. Such efforts can have a positive impact on patients and learners, and enhance the teaching skills of future faculty. PMID- 26835746 TI - Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases. AB - Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed. PMID- 26835750 TI - Establishment of Canine-Derived Giardia duodenalis Isolates in Culture. AB - Researchers continue to rely on axenic cultivation of Giardia duodenalis trophozoites in vitro to study the life cycle and host-parasite interactions of G. duodenalis and to develop vaccines and drugs to prevent and treat giardiasis. The majority of in vitro studies of G. duodenalis have used a small subset of isolates, mostly of assemblage A, and these isolates are usually originally isolated from humans. The most commonly used isolate for lab studies is known as WB. Canine giardiasis is a disease of veterinary importance, but it may also be of relevance in zoonotic transmission. Few G. duodenalis isolates from dogs have been adapted to in vitro culture, probably because the methods used are not suitable for the canine-specific genotypes that tend to dominate in most dog populations. In the current study, an experimental approach to cultivating canine derived isolates of G. duodenalis was attempted by modification of the standard protocol based on physiological differences between the human and canine digestive system. An adapted method is described for improving the rate of in vitro excystation of cysts isolated from dogs by chemically weakening the cyst wall. A new canine-derived assemblage A G. duodenalis isolate was successfully adapted to axenic culture by using this method; the dog apparently had a mixed infection of assemblages A and D, but the assemblage A successfully outcompeted the assemblage D under conditions of in vitro culture. Based on the results, reasons regarding why humans do not seem to be suitable hosts for G. duodenalis in assemblages C and D are discussed. PMID- 26835751 TI - Small interfering RNA expression inhibits avian infectious bronchitis virus replication and inflammatory response. AB - BACKGROUND: Avian infectious bronchitis virus (IBV) is a major cause of poor weight gain and mortality among chicks. METHODS: A lentivirus vector was used to generate transgenic chickens expressing small interfering RNA (siRNA) targeting the M protein of IBV. Offspring of generation 0 (G0) were screened to identify G1 transgenic chickens (Tg). Monocytes from G1 Tg were stimulated with IBV in vitro. RESULTS: Monocytes producing siRNA efficiently inhibit IBV replication. Expression of inflammatory cytokines, Mx protein and nitric oxide levels were lower in early IBV infection in Tg. In vivo experiments show that siRNA expression inhibits IBV replication, significantly decreases mortality and increases weight gain. Inflammatory responses and oxidative damage were significantly decreased, yielding minimal tissue injury. The inflammatory responses indicate that the cellular immune response is most effective during the initial stage, while the humoral immune response is more significant in later stages of infection. CONCLUSIONS: Small interfering RNA expression inhibits avian IBV replication and inflammatory response. PMID- 26835752 TI - Parathyroid hormone, cardiovascular and all-cause mortality: A meta-analysis. AB - BACKGROUND: Inconsistent findings have reported on parathyroid hormone (PTH) concentration and cardiovascular or all-cause mortality. OBJECTIVE: To investigate whether elevated PTH concentration was an independent predictor for cardiovascular or all-cause mortality in the general population by conducting a meta-analysis based on prospective studies. METHOD: We searched Cochrane Library, Pubmed, and Embase databases up to June 2015. Only prospective studies evaluating serum PTH concentration and cardiovascular or all-cause mortality were included. Pooled adjust risk ratio (RR) and corresponding 95% confidence intervals (CI) were calculated for the highest vs. lowest PTH concentration. RESULTS: Ten studies with 31,616 subjects were identified and analyzed. Compared the highest to the lowest PTH concentration, elevated serum PTH concentration increased the risk of all-cause mortality (RR 1.19; 95% CI 1.08-1.30) but not for cardiovascular mortality (RR 1.26; 95% CI 0.96-1.66). Subgroup analyses indicated that cardiovascular mortality risk appeared to be more pronounced among men (RR 1.68; 95% CI 1.05-2.67). CONCLUSIONS: Elevated PTH concentration is an independent predictor of all-cause mortality. Elevated serum PTH concentration appears to increase risk of cardiovascular mortality among men. PMID- 26835754 TI - Simulated Solute Tempering in Fully Polarizable Hybrid QM/MM Molecular Dynamics Simulations. AB - We successfully apply a solute tempering approach, which substantially reduces the large number of temperature rungs required in conventional tempering methods by solvent charge scaling, to hybrid molecular dynamics simulations combining quantum mechanics with molecular mechanics (QM/MM). Specifically, we integrate a combination of density functional theory (DFT) and polarizable MM (PMM) force fields into the simulated solute tempering (SST) concept. We show that the required DFT/PMM-SST weight parameters can be obtained from inexpensive calculations and that for alanine dipeptide (DFT) in PMM water three rungs suffice to cover the temperature range from 300 to 550 K. PMID- 26835753 TI - Spectral analysis of intracranial pressure: Is it helpful in the assessment of shunt functioning in-vivo? AB - OBJECTIVE: Shunt failure is common in hydrocephalic patients. The cerebrospinal fluid (CSF) infusion test enables the assessment of CSF absorption capacity, which is represented by the resistance to CSF outflow (ROUT) However, shunt failure may not only affect the CSF absorption capacity but also the intracranial compliance or compensatory properties. Spectral analysis of the ICP signal obtained during the infusion test may enable the comprehensive assessment of the overall deterioration caused by shunt failure. MATERIAL AND METHODS: A total of 121 hydrocephalic shunted patients underwent the infusion test with continuous intracranial pressure (ICP) and arterial blood pressure (ABP) recording. The maximum amplitudes of three major frequency bandwidths (0.2-2.6, 2.6-4.0 and 4.0 15 Hz, respectively) were calculated from the ICP. Statistical analyses were conducted to identify factors significantly associated with shunt failure, to construct an index (i.e., the shunt response parameter, SRP) for detecting shunt failure, and to define thresholds for ROUT and SRP. RESULTS: The ROUT threshold for detecting shunt failure was 7.59 mmHg/ml/min, and this threshold showed an accuracy of 82.64%. All spectral parameters were found to be significantly associated with shunt patency (p<0.05). The SRP exhibited significantly better accuracy than ROUT in detecting shunt failure (91.74%). CONCLUSION: The hydrodynamic assessment of shunted patients enhanced by spectral analysis during the infusion test detected shunt failure with high accuracy. Although further validation is needed, the SRP exhibited promising results. PMID- 26835755 TI - Fabrication of plasmonic Au/TiO2 nanofiber films with enhanced photocatalytic activities. AB - TiO2 nanofiber films (TiO2 NFF) with visible light scattering ability were prepared using a hydrothermal method. Au nanoparticles (Au NPs) were then deposited on the surface of TiO2 film using a microwave-assisted chemical reduction process. An overlapped light-trapping phenomenon was observed in Au/TiO2 NFF due to the light-scattering nanostructures of TiO2 film and the localized surface plasmon resonance (LSPR) of Au NPs. The MB degradation over the composite films is much faster than that of pure TiO2 film. The enhanced photocatalytic activity is primarily attributed to the charge transfer property and the overlapped light-trapping nanostructures of Au/TiO2. PMID- 26835756 TI - Weak two-photon absorption applied to the rapid prototyping of cell scaffolds. AB - Two-photon polymerization (TPP) has been employed to generate deep structures using the biocompatible and optically transparent monomer ethoxylated bisphenol A dimethacrylate (EO=6) (EBPADMA) and 4, 4'-Bis(diethylamino)benzophenon as the photoinitiator. The two-photon absorption cross section of the initiator was measured to be 1 GM (1 GM=1*10(-50) cm(4) s photon(-1)) in EBPADMA. Here we have explored a weak absorption regime whereby deep structures (~300 MUm) can be generated in a single pass. This allows rapid fabrication of structures suitable for cell scaffolds where the length scales are small, ~10 MUm, but are required over long ranges, ~cm. The dependence of the TPP properties on the writing power, speed, exposure time and NA, of the focusing lens were studied in detail. Diffraction calculations for the focusing optics employed show that spherical aberration plays a significant role in determining the feature sizes achieved. PMID- 26835757 TI - Self-mixing interferometry for rotational speed measurement of servo drives. AB - Self-mixing interferometry (SMI) is an efficient technique applied to measure distance, velocity, displacement, and vibration. In this work, a compact and low cost SMI is applied to measure the rotational speed of a servo drive up to 6000 RPM. The application of SMI to rotational speed measurement of servo drives instead of the usage of incremental encoders is proposed. The Doppler frequency is obtained via analysis on the power spectral density, which is estimated by the smoothing periodogram method based on the fast Fourier transformation. The signals are processed in MATLAB and LABVIEW, showing that the SMI can be applied to dynamic rotational speed measurement of servo drives. Results of experiments demonstrate that this system is implementable for rotational speed measurement over the whole range from 3 RPM to 6000 RPM. In addition, the system used to measure rotational speed can also accurately record changes in position without integrating the velocity. PMID- 26835758 TI - Underwater gas pipeline leakage source localization by distributed fiber-optic sensing based on particle swarm optimization tuning of the support vector machine. AB - Accurate underwater gas pipeline leak localization requires particular attention due to the sensitivity of environmental conditions. Experiments were performed to analyze the localization performance of a distributed optical fiber sensing system based on the hybrid Sagnac and Mach-Zehnder interferometer. The traditional null frequency location method does not easily allow accurate location of the leakage points. To improve the positioning accuracy, the particle swarm optimization algorithm (PSO) tuning of the support vector machine (SVM) was used to predict the leakage points based on gathered leakage data. The PSO is able to optimize the SVM parameters. For the 10 km range chosen, the results show the PSO-SVM average absolute error of the leakage points predicted is 66 m. The prediction accuracy of leakage points is 98.25% by PSO tuning of the SVM processing. For 20 leakage test data points, the average absolute error of leakage point location is 124.8 m. The leakage position predicted by the PSO algorithm after optimization of the parameters is more accurate. PMID- 26835759 TI - Low-noise and high-gain Brillouin optical amplifier for narrowband active optical filtering based on a pump-to-signal optoelectronic tracking. AB - We implement and characterize an optical narrowband amplifier based on stimulated Brillouin scattering with pump-to-signal relative frequency fluctuations overcome thanks to an active pump tracking. We achieve a precise characterization of this amplifier in terms of gain and noise degradation (noise figure). The performances of this stable selective amplification are compared to those of a conventional erbium-doped fiber amplifier in order to highlight the interest of the Brillouin amplification solution for active narrow optical filtering with a bandpass of 10 MHz. Thanks to the simple optoelectronic pump-to-signal tracking, the Brillouin active filter appears as a stable and reliable solution for narrowband optical processing in the coherent optical communication context and optical sensor applications. PMID- 26835760 TI - Laser-induced breakdown spectroscopy determination of toxic metals in fresh fish. AB - A method based on laser induced breakdown spectroscopy (LIBS) for monitoring lead and copper accumulation in edible fish, particularly "tilapia del Nilo" (Oreochromis niloticus) is presented. The capability of this analytical method is compared with results obtained by atomic absorption spectrometry. Detection limits by LIBS are 25 parts per million (ppm) for Pb and 100 ppm for Cu, values that are below the maximum permissible levels of some international standards. Application of LIBS detection allows the development of portable instruments for contamination control of edible fish. PMID- 26835761 TI - Optical tweezing by photomigration. AB - Photomigration in azo polymers is an area of research that witnessed intensive studies owing to its potential in optical manipulation, e.g., optical tweezing, the physical mechanism of which remains unsolved since its discovery about two decades ago. In this paper, a detailed theoretical study that reproduces the phenomena associated with photomigration is presented, including the physical models and the associated master equations. Polarization effects are discussed and analytical solutions are given to describe the steady-state and the dynamics of photomigration. Such a theory leads to new theoretical experiments relating material properties to light action. A photoisomerization force which is described by a spring-type model is introduced. This force is derived from a harmonic light potential that moves the azo polymer. This force is parenting to optical tweezers, but it is quite different in the sense that it requires photoisomerization to occur. The azo polymer's motion is governed by four competing forces: the photoisomerization force, and the restoring optical gradient and elastic forces, as well as the random forces due to spontaneous diffusion. PMID- 26835762 TI - Quantitative two-dimensional measurement of oil-film thickness by laser-induced fluorescence in a piston-ring model experiment. AB - This paper describes advances in using laser-induced fluorescence of dyes for imaging the thickness of oil films in a rotating ring tribometer with optical access, an experiment representing a sliding piston ring in an internal combustion engine. A method for quantitative imaging of the oil-film thickness is developed that overcomes the main challenge, the accurate calibration of the detected fluorescence signal for film thicknesses in the micrometer range. The influence of the background material and its surface roughness is examined, and a method for flat-field correction is introduced. Experiments in the tribometer show that the method yields quantitative, physically plausible results, visualizing features with submicrometer thickness. PMID- 26835764 TI - Generation of more than 40 W of average output power from a passively Q-switched Yb-doped fiber laser. AB - We report on the generation of 41.6 W of average output power from a passively Q switched ytterbium-doped fiber laser using Cr4+:YAG crystal as a saturable absorber (SA). This is the highest average power from passively Q-switched fiber lasers reported so far in the literature, to our knowledge, and it has been achieved by using a specially designed T-type double-end pumping configuration. Variation in average output power, pulse energy, pulse duration, pulse frequency, and pulse-to-pulse stability has also been studied using SAs of different linear transmissions. The effect of an intracavity SA on self-pulsing dynamics was also investigated and it was observed that, at lower input pump power near threshold, the presence of an SA enhances the peak power of relaxation oscillations to trigger the generation of stimulated Raman scattering in the gain fiber. With an increase in pump power, when the passive Q-switching threshold is reached, high peak power random self-pulses regenerate into low amplitude regular Q-switched pulses. The effect of the length of the gain medium on dual-wavelength generation at very low input pump power and broadband generation at sufficiently higher pump power has also been explored. PMID- 26835763 TI - Fabrication and application of heterogeneous printed mouse phantoms for whole animal optical imaging. AB - This work demonstrates the usefulness of 3D printing for optical imaging applications. Progress in developing optical imaging for biomedical applications requires customizable and often complex objects for testing and evaluation. There is therefore high demand for what have become known as tissue-simulating "phantoms." We present a new optical phantom fabricated using inexpensive 3D printing methods with multiple materials, allowing for the placement of complex inhomogeneities in complex or anatomically realistic geometries, as opposed to previous phantoms, which were limited to simple shapes formed by molds or machining. We use diffuse optical imaging to reconstruct optical parameters in 3D space within a printed mouse to show the applicability of the phantoms for developing whole animal optical imaging methods. This phantom fabrication approach is versatile, can be applied to optical imaging methods besides diffusive imaging, and can be used in the calibration of live animal imaging data. PMID- 26835765 TI - Spectral broadening in high-power Yb-doped fiber lasers employing narrow linewidth multilongitudinal-mode oscillators. AB - High-power continuous wave fiber lasers with narrow linewidths are required for spectral beam combining systems. A 2.9 kW Yb-doped fiber laser with an output linewidth as narrow as 0.31 nm employing a narrow-linewidth multilongitudinal mode oscillator is experimentally demonstrated. The numerical simulations reveal that the spectral broadening of the bandwidth grows almost linearly with injected mode number, which provides a potential way to further suppress the nonlinear spectral broadening in high-power fiber lasers. PMID- 26835766 TI - Graphite saturable absorber based on the pencil-sketching method for Q-switching of an erbium fiber laser. AB - We experimentally demonstrate a practical and simple method for the preparation of a graphite-based, fiberized saturable absorber (SA). Our SA is prepared by using a low-cost graphite-core pencil that is commercially available from stationary stores to uniformly shade the flat end of a fiber ferrule. The saturable-absorption performance of the prepared SA was experimentally tested, and the feasibility of using the SA as a passive Q-switch was investigated through its incorporation into an erbium-doped-fiber ring cavity. The modulation depth of the SA is ~1%, and the Q-switched pulses of a 1.98 MUs temporal width were readily obtained at a repetition rate of 46.08 kHz. PMID- 26835767 TI - Measurement of the surface form error of large aperture plane optical surfaces with a polarization phase-shifting liquid reference reflection Fizeau interferometer. AB - A polarization phase-shifting liquid reference reflection Fizeau interferometer has been proposed. A polarization cyclic path optical configuration along with a concave telescope mirror is used to produce a pair of expanded, collimated p and s polarized beams with a small angular separation between them. The collimated beams are deflected along a vertical direction toward a Fizeau interferometer cavity formed between a liquid surface that acts as a reference surface and a plane test surface. Either the p or s polarized beam is allowed to strike the liquid surface normally and the orientation of the test surface is adjusted to reflect the other beam, having orthogonal linear polarization, in the direction of the normally reflected reference beam from the liquid surface. A combination of a quarter-wave plate and linear polarizer is used to apply polarization phase shift between the test and reference beams, and quantitative surface form error is measured by applying phase-shifting interferometry. A method for elimination of the residual system aberration is discussed. Results obtained for an optically polished BK-7 disk of clear aperture diameter ~160 mm are presented. PMID- 26835768 TI - Alignment-free characterization of 2D gratings. AB - Fast characterization of 2D gratings is demonstrated using a Fourier lens optical system and a differential optimization algorithm. It is shown that the grating specific parameters such as the basis vectors and the angle between them, along with the alignment of the sample, such as the rotation of the sample around the x, y, and z axis, can be deduced from a single measurement. More specifically, the lattice vectors and the angle between them have been measured, while the corrections of the alignment parameters are used to improve the quality of the measurement and, hence, reduce the measurement uncertainty. Alignment-free characterization is demonstrated on a 2D hexagonal grating with a period of 700 nm and a checkerboard grating with a pitch of 3000 nm. The method also can be used for automatic alignment and in-line characterization of gratings. PMID- 26835769 TI - Performance of the Gemini Planet Imager's adaptive optics system. AB - The Gemini Planet Imager's adaptive optics (AO) subsystem was designed specifically to facilitate high-contrast imaging. A definitive description of the system's algorithms and technologies as built is given. 564 AO telemetry measurements from the Gemini Planet Imager Exoplanet Survey campaign are analyzed. The modal gain optimizer tracks changes in atmospheric conditions. Science observations show that image quality can be improved with the use of both the spatially filtered wavefront sensor and linear-quadratic-Gaussian control of vibration. The error budget indicates that for all targets and atmospheric conditions AO bandwidth error is the largest term. PMID- 26835770 TI - Alignment tolerant expanded beam connector based on a gapless fiber-lens interface. AB - An expanded beam connector (EBC) has been proposed and realized, where a single mode fiber is seamlessly integrated with a ball lens exhibiting a near-zero back focal length (BFL) so that the incoming small mode exiting the fiber translates into an enlarged collimated beam via the lens. The structural tolerance for the fiber-optic connector is primarily relaxed by relieving the restrictions imposed on the meticulous control of the gap between the lens and the fiber. The EBC has been designed through rigorous ray-optic simulations and then constructed based on a ball lens in LASF35 (n=~1.98 at lambda=1.3 MUm), exhibiting an ultrashort BFL of ~13 MUm. It was practically confirmed that an input mode of a ~10 MUm spot relating to the single-mode fiber could be efficiently converted into a highly collimated beam of a ~350 MUm spot that emanates from the ball lens, leading to a 35-fold beam expansion. The alignment tolerance for the fiber as well as the connector unit was scrutinized with respect to the angular tilt and transverse displacement. The measured insertion loss for the EBC, allowing for no separation between the fiber and ball lens, was slightly over 0.8 dB. PMID- 26835771 TI - Starting configuration design method of freeform imaging and afocal systems with a real exit pupil. AB - Optical system configurations with a real exit pupil have important applications. However, there are few effective design methods of these systems for choice, especially for the systems using freeform surfaces. In this paper, we propose a novel starting configuration design method of freeform optical systems with a real exit pupil before the image plane. This method works for both the cases of imaging systems with optical power and afocal systems. Each single freeform surface in the starting configuration is generated directly using the light rays of multiple fields and different pupil coordinates. With a proposed multi-step design strategy, not only the given system specifications and the desired object image relationships (or magnification for the afocal system) are achieved, the generation of a real, small-distorted exit pupil with a given size and shape (which means the imaging relationships of the pupils) can be also considered. The system generated by this method can be taken as a good starting configuration for further optimization. The benefits and feasibility of this design method are demonstrated by two design examples. One example is a freeform off-axis three mirror imaging system. The other example is a freeform off-axis three-mirror afocal telescope. Both of the systems have a modulation transfer function (MTF) that is closed to the diffraction limit. PMID- 26835772 TI - Period-chirped gratings fabricated by laser interference lithography with a concave Lloyd's mirror. AB - We developed a laser interference lithography (LIL) system for fabrication of period-chirped gratings, which would be useful for sophisticated optical components. Despite its simplicity, the developed LIL system, based on a Lloyd's mirror interferometer with a cylindrically concave mirror, can generate chirped gratings, yet over a large area at high throughput owing to the nature of LIL. We have derived exact theoretical equations needed for system design, built the LIL system, and subsequently realized period-chirped gratings. A fabricated sample whose center period is Lambda~600 nm exhibits a continuous period variation of DeltaLambda=92 nm across 17 mm width. PMID- 26835773 TI - Differential time domain method improves performance of pulsed laser ranging and three-dimensional imaging. AB - A ranging method based on the differential time domain method (DTDM) is proposed in order to improve ranging accuracy and the range of active measurement based on peak discriminator (PD). We develop mathematical models and deduce that zero crossing sensitivity is an important factor, which affects the ranging error of DTDM. Additionally, zero-crossing sensitivity is determined by delayed time. We carried out relative experiments and obtained the smallest ranging error when delayed time is receiving pulse width. We also compare ranging, three-dimensional (3D) point clouds and depth images based on two methods under same testing conditions. The results show that DTDM is beneficial in improving performance of pulse laser ranging and 3D imaging. PMID- 26835774 TI - Nonbulk motion system for simultaneously measuring the refractive index and thickness of a sample using tunable optics and spatial signal processing-based Gaussian beam imaging. AB - This paper presents a novel approach to simultaneously measuring the thickness and refractive index of a sample. The design uses an electronically controlled tunable lens (ECTL) and a microelectromechanical-system-based digital micromirror device (DMD). The method achieves the desired results by using the DMD to characterize the spatial profile of a Gaussian laser beam at different focal length settings of the ECTL. The ECTL achieves tunable lensing through minimal motion of liquid inside a transparent casing, whereas the DMD contains an array of movable micromirrors, which make it a reflective spatial light modulator. As the proposed system uses an ECTL, a DMD, and other fixed optical components, it measures the thickness and refractive index without requiring any motion of bulk components such as translational and rotational stages. A motion-free system improves measurement repeatability and reliability. Moreover, the measurement of sample thickness and refractive index can be completely automated because the ECTL and DMD are controlled through digital signals. We develop and discuss the theory in detail to explain the measurement methodology of the proposed system and present results from experiments performed to verify the working principle of the method. Refractive index measurement accuracies of 0.22% and 0.2% were achieved for two BK-7 glass samples used, and the thicknesses of the two samples were measured with a 0.1 mm accuracy for each sample, corresponding to a 0.39% and 0.78% measurement error, respectively, for the aforementioned samples. PMID- 26835775 TI - Support-domain constrained phase retrieval algorithms in terahertz in-line digital holography reconstruction of a nonisolated amplitude object. AB - Phase retrieval algorithms applied to in-line digital holography reconstruction can weaken interference from the region outside the study target and an unstable light source, etc., by adopting the object-plane support domain constraint. Based on threshold segmentation and morphological filtering, a method to directly calculate the object-plane support domain is proposed in this paper. Combined with the above method, an improved support-domain constrained phase retrieval algorithm is presented. Then, imaging simulations and experiments on terahertz in line digital holography reconstruction of nonisolated objects are conducted. The simulations study the influence of transmittance of the background plate, structural element of morphological filtering, etc., on the reconstruction effect of the improved algorithm without noise interference. Simulation and experiment results suggest that good reconstructed images can be obtained by this algorithm when transmittance of the background plate is greater than 0.90. PMID- 26835776 TI - Invalid phase values removal method for absolute phase recovery. AB - A novel approach is presented for more effectively removing invalid phase values in absolute phase recovery. The approach is based on a detailed study involving the types and cases of invalid phase values. Meanwhile, some commonalities of the existing removal algorithms also are thoroughly analyzed. It is well known that rough absolute phase and fringe order maps can very easily be obtained by temporal phase unwrapping techniques. After carefully analyzing the components and fringe order distribution of the rough fringe order map, the proposed method chiefly adopts an entirely new strategy to refine a pure fringe order map. The strategy consists of three parts: (1) the square of an image gradient, (2) subregion areas of the binary image, and (3) image decomposition and composition. In combination with the pure fringe order map and a removal criterion, the invalid phase values can be identified and filtered out from the rough absolute phase map. This new strategy not only gets rid of the limitations of traditional removal methods but also has a two-fold function. The paper also offers different metrics from the experiment to evaluate the quality of the final absolute phase. In contrast with other removal methods, experimental results have verified the feasibility, effectiveness, and superiority of the proposed method. PMID- 26835777 TI - Packaged optofluidic microbubble resonators for optical sensing. AB - A microbubble resonator (MBR) coupled with a fiber taper is packaged with low index polymer. The cladding polymer serves as a protective matrix for the coupling system to avoid environmental disturbance. The packaged structure is portable and provides good performance to maintain high Q factors for a long working period. The hollow structure of the MBR makes the packaged system useful for practical chemical and biomedical sensing applications. To evaluate the performance of the packaged MBRs-based sensor, we carry out bulk refractive index and surface-sensing measurements with achieved sensitivities of 18.8 nm/RIU and 31.29 pm/nm, respectively. PMID- 26835779 TI - Box-like filter response using multimode single-ring microresonators. AB - In this work we suggest a new technique to form a box-like filter response using a single microring resonator. The new design is based on exploiting the multimode propagation in the ring. The technique is implemented in the case of a two-mode ring resonator for different designs. The obtained results show that the new designs allow getting 1 to 10 dB spectral width shape factor better than 0.4, as verified by the FDTD simulation at different wavelengths and for different spectral widths. This new design methodology opens the door for more compact optical filters with controlled box-like response. PMID- 26835778 TI - Detection of citrus canker and Huanglongbing using fluorescence imaging spectroscopy and support vector machine technique. AB - Citrus canker and Huanglongbing (HLB) are citrus diseases that represent a serious threat to the citrus production worldwide and may cause large economic losses. In this work, we combined fluorescence imaging spectroscopy (FIS) and a machine learning technique to discriminate between these diseases and other ordinary citrus conditions that may be present at citrus orchards, such as citrus scab and zinc deficiency. Our classification results are highly accurate when discriminating citrus canker from citrus scab (97.8%), and HLB from zinc deficiency (95%). These results show that it is possible to accurately identify citrus diseases that present similar symptoms. PMID- 26835781 TI - Happy New Year: editorial. AB - Editor-in-Chief Ron Driggers welcomes a new year. PMID- 26835780 TI - Estimation of spectral distribution of sky radiance using a commercial digital camera. AB - Methods for estimating spectral distribution of sky radiance from images captured by a digital camera and for accurately estimating spectral responses of the camera are proposed. Spectral distribution of sky radiance is represented as a polynomial of the wavelength, with coefficients obtained from digital RGB counts by linear transformation. The spectral distribution of radiance as measured is consistent with that obtained by spectrometer and radiative transfer simulation for wavelengths of 430-680 nm, with standard deviation below 1%. Preliminary applications suggest this method is useful for detecting clouds and studying the relation between irradiance at the ground and cloud distribution. PMID- 26835783 TI - Do we need a third mechanistic descriptor for chronic pain states? PMID- 26835782 TI - Preliminary validation of the Michigan Body Map. AB - We developed the Michigan Body Map (MBM) as a self-report measure to assess body areas where chronic pain is experienced and to specifically quantify the degree of widespread body pain when assessing for centralized pain features (eg, fibromyalgia-like presentation). A total of 402 patients completed the measure in 5 distinct studies to support the validation of the original and a revised version of the MBM. Administration is rapid 39 to 44 seconds, and errors for the original MBM were detected in only 7.2% of the possible body areas. Most errors underestimated the number of painful areas or represented confusion in determining the right vs left side. The MBM was preferred (P = 0.013) and felt to better depict pain location (P = 0.001) when compared with the Widespread Pain Index checklist of the 2011 Fibromyalgia Survey Criteria, but participants did not express any preference between the MBM and Brief Pain Inventory body map. Based on the data from the first 3 studies, a revised version of the MBM was created including a front and back body image and improved guidance on right sidedness vs left. The revised MBM was preferred when compared with the original and was more accurate in depicting painful body areas (P = 0.004). Furthermore, the revised MBM showed convergent and discriminant validity with other self report measures of pain, mood, and function. In conclusion, the MBM demonstrated utility, reliability, and construct validity. This new measure can be used to accurately assess the distribution of pain or widespread bodily pain as an element of the fibromyalgia survey score. PMID- 26835784 TI - Somatosensory phenotyping for better translation in neuropathic pain? PMID- 26835785 TI - Comparing Vibrationally Averaged Nuclear Shielding Constants by Quantum Diffusion Monte Carlo and Second-Order Perturbation Theory. AB - Using the method of modified Shepard's interpolation to construct potential energy surfaces of the H2O, O3, and HCOOH molecules, we compute vibrationally averaged isotropic nuclear shielding constants ?sigma? of the three molecules via quantum diffusion Monte Carlo (QDMC). The QDMC results are compared to that of second-order perturbation theory (PT), to see if second-order PT is adequate for obtaining accurate values of nuclear shielding constants of molecules with large amplitude motions. ?sigma? computed by the two approaches differ for the hydrogens and carbonyl oxygen of HCOOH, suggesting that for certain molecules such as HCOOH where big displacements away from equilibrium happen (internal OH rotation), ?sigma? of experimental quality may only be obtainable with the use of more sophisticated and accurate methods, such as quantum diffusion Monte Carlo. The approach of modified Shepard's interpolation is also extended to construct shielding constants sigma surfaces of the three molecules. By using a sigma surface with the equilibrium geometry as a single data point to compute isotropic nuclear shielding constants for each descendant in the QDMC ensemble representing the ground state wave function, we reproduce the results obtained through ab initio computed sigma to within statistical noise. Development of such an approach could thereby alleviate the need for any future costly ab initio sigma calculations. PMID- 26835786 TI - Carbon Nanotube Interconnects Realized through Functionalization and Sintered Silver Attachment. AB - Carbon nanotubes (CNTs) in the form of interconnects have many potential applications, and their ability to perform at high temperatures gives them a unique capability. We show the development of a novel transfer process using CNTs and sintered silver that offers a unique high-temperature, high-conductivity, and potentially flexible interconnect solution. Arrays of vertically aligned multiwalled carbon nanotubes of approximately 200 MUm in length were grown on silicon substrates, using low-temperature photothermal chemical vapor deposition. Oxygen plasma treatment was used to introduce defects, in the form of hydroxyl, carbonyl, and carboxyl groups, on the walls of the carbon nanotubes so that they could bond to palladium (Pd). Nanoparticle silver was then used to bind the Pd coated multiwalled CNTs to a copper substrate. The silver-CNT-silver interconnects were found to be ohmic conductors, with resistivity of 6.2 * 10(-4) Omegam; the interconnects were heated to temperatures exceeding 300 degrees C (where common solders fail) and were found to maintain their electrical performance. PMID- 26835787 TI - To involvement the conformation of the adenine nucleotide translocase in opening the Tl(+)-induced permeability transition pore in Ca(2+)-loaded rat liver mitochondria. AB - The conformation of adenine nucleotide translocase (ANT) has a profound impact in opening the mitochondrial permeability transition pore (MPTP) in the inner membrane. Fixing the ANT in 'c' conformation by phenylarsine oxide (PAO), tert butylhydroperoxide (tBHP), and carboxyatractyloside as well as the interaction of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS) with mitochondrial thiols markedly attenuated the ability of ADP to inhibit the MPTP opening. We earlier found (Korotkov and Saris, 2011) that calcium load of rat liver mitochondria in medium containing TlNO3 and KNO3 stimulated the Tl(+)-induced MPTP opening in the inner mitochondrial membrane. The MPTP opening as well as followed increase in swelling, a drop in membrane potential (DeltaPsimito), and a decrease in state 3, state 4, and 2,4-dinitrophenol-uncoupled respiration were visibly enhanced in the presence of PAO, tBHP, DIDS, and carboxyatractyloside. However, these effects were markedly inhibited by ADP and membrane-penetrant hydrophobic thiol reagent, N-ethylmaleimide (NEM) which fix the ANT in 'm' conformation. Cyclosporine A additionally potentiated these effects of ADP and NEM. Our data suggest that conformational changes of the ANT may be directly involved in the opening of the Tl(+)-induced MPTP in the inner membrane of Ca(2+)-loaded rat liver mitochondria. Using the Tl(+)-induced MPTP model is discussed in terms finding new transition pore inhibitors and inducers among different chemical and natural compounds. PMID- 26835789 TI - Folding of Protein L with Implications for Collapse in the Denatured State Ensemble. AB - A fundamental question in protein folding is whether the coil to globule collapse transition occurs during the initial stages of folding (burst phase) or simultaneously with the protein folding transition. Single molecule fluorescence resonance energy transfer (FRET) and small-angle X-ray scattering (SAXS) experiments disagree on whether Protein L collapse transition occurs during the burst phase of folding. We study Protein L folding using a coarse-grained model and molecular dynamics simulations. The collapse transition in Protein L is found to be concomitant with the folding transition. In the burst phase of folding, we find that FRET experiments overestimate radius of gyration, Rg, of the protein due to the application of Gaussian polymer chain end-to-end distribution to extract Rg from the FRET efficiency. FRET experiments estimate ~6 A decrease in Rg when the actual decrease is ~3 A on guanidinium chloride denaturant dilution from 7.5 to 1 M, thereby suggesting pronounced compaction in the protein dimensions in the burst phase. The ~3 A decrease is close to the statistical uncertainties of the Rg data measured from SAXS experiments, which suggest no compaction, leading to a disagreement with the FRET experiments. The transition state ensemble (TSE) structures in Protein L folding are globular and extensive in agreement with the Psi-analysis experiments. The results support the hypothesis that the TSE of single domain proteins depends on protein topology and is not stabilized by local interactions alone. PMID- 26835790 TI - Up-Regulation of Plasma miR-23b is Associated with Poor Prognosis of Gastric Cancer. AB - BACKGROUND: Gastric cancer (GC) is a common malignant disease and microRNAs (miRNAs) have been shown to play important roles in GC tumorigenesis. As the clinical outcome of GC is closely correlated with the clinical stage at the time of diagnosis, early detection and prevention are crucial. This study was designed to evaluate the expression level of plasma miR-23b in patients with GC and investigate the relationship between plasma miR-23b expression level and the prognosis of GC. MATERIAL/METHODS: We recruited 138 patients diagnosed with GC and 50 healthy volunteers. Quantitative real-time PCR (qRT-PCR) was performed to evaluate the expression level of plasma miR-23b in all participants. The association between miR-23b expression and clinicopathological factors as well as survival rates was analyzed. Receiver operator curve (ROC) analysis was carried out to evaluate the diagnostic performance of plasma miR-23b for GC.Univariate and multivariate Cox regression analyses were conducted to determine whether plasma miR-23b was an independent predictor of survival. RESULTS: The expression levels of miR-23b were upregulated in plasma samples from GC patients (P<0.01) and were significantly associated with T stage, distant metastasis, and differentiation. Significantly shorter 5-year overall survival (OS) and disease free survival (DFS) were observed in patients with higher expression of the miR 23b (P<0.01). The area under the curve (AUC) of high expression of plasma miR-23b to diagnose GC was 0.80 (95% CI: 0.74-0.86, P<0.001). Multivariate analysis revealed that enhanced expression of plasma miR-23b was an independent predictor of OS (P=0.015) and DFS (P=0.004). CONCLUSIONS: Our results indicated that plasma miR-23b was overexpressed in GC patients and high plasma miR-23b expression was associated with poor clinical outcome. Thus, plasma miR-23b may serve as a potential diagnostic biomarker and therapeutic target for GC. PMID- 26835788 TI - The Promising Nanocarrier for Doxorubicin and siRNA Co-delivery by PDMAEMA-based Amphiphilic Nanomicelles. AB - Synergistic effects of anticancer drug and siRNA have displayed superior advantages for cancer therapy. Herein, we deeply analyzed the feasibility that whether doxorubicin (DOX) and siRNA could be co-delivered by mPEG-PCL-graft PDMAEMA (PECD) micelles, which mediated excellent DNA/siRNA delivery in vitro and in vivo reported in our previous work. DOX-loaded NPs (PECD-D) were developed by nanoprecipitation technology and exhibited high drug loading content (DLC, 9.5%). In vitro cytotoxicity study in MDA-MB-231 cells, PECD-D treated groups had lower IC50 compared to free DOX groups (F-DOX) at different transfection time (24, 48, and 72h), which maybe attribute to its high cellular uptake and endosomal escape properties. The speculation was confirmed with the results of drug release profile in acidic media, flow cytometry analysis and confocal images. Futhermore, Cy5 labeled siRNA was introduced in PECD-D micelles (PECD-D/siRNA) to track the behavior of dual-loaded nanodrug in vitro and in vivo. Flow cytometry analysis presented that DOX and siRNA were successfully co-delivered into cells, the positive cells ratio were 94.6 and 99.5%, respectively. Confocal images showed that not only DOX and siRNA existed in cytoplasm, but DOX traversed endosome/lysosome and entered into cell nucleus. For in vivo tumor-targeting evaluation in BALB/c nude mice, both DOX and Cy5-siRNA could be detected in tumor sites after intravenous injection with PECD-D/siRNA formulation. Therefore, we believed that PECD micelles have a potential ability as DOX and siRNA co-delivery carrier for cancer therapy. PMID- 26835792 TI - Hand and wrist surgery: study of efficacy about a new way for one-day low complexity surgery. AB - BACKGROUND: In our Hand Micro-surgery Department surgery procedures identified by some regional legislation as "low-complexity care interventions" (BOCA) are carry out. For this reason, as pilot experience, it has been decided to apply Diagnostic Therapeutic Path (DTP) to this type of surgeries in order to improve the offered service. METHODS: From 2011 to 2012 we collected data about 410 BOCA procedures and we monitored a series of indicators. RESULTS: The patients were classified as ASA score 1-2 (99%) and they had a postoperative observation time less than 24h (95%). They reported a constant reduction of pain in the days after surgery (VAS <= 4). In 27 cases were found post-surgical complications. All patients evaluated positively this DTP. CONCLUSIONS: The obtained results were used to improve the activity in others Departments of our Institute. PMID- 26835793 TI - Dental unit water treatment with hydrogen peroxide and monovalent silver ions artificially contaminated with freshly isolated pathogens. AB - BACKGROUND: Dental unit water (DUW) could be contaminated by human pathogens coming from biological fluids penetrated during patient treatment and by opportunistic pathogens detached from aquatic biofilm. These microorganisms could be spread to following patients. We tested the disinfectant activity of hydrogen peroxide and monovalent silver ions (H(2)O(2)-Ag(+)) into DUW artificially contaminated with freshly isolated pathogens. METHODS: The tested microorganisms were Staphylococcus aureus, Enterococcus faecalis, Candida albicans, Pseudomonas aeruginosa, Legionella pneumophila, Mycobacterium chelonae, non-pathogenic Bacillus clausii spores. Bacterial suspensions were inoculated into the waterlines of pre-sterilized dental turbines. The test-turbines were connected to DUW and contaminated water was treated for 10 minutes with H(2)O(2)-Ag(+)-based disinfectant (H(2)O(2) 3% v/v, Ag(+) 0.001% w/v). The control-turbines were left untreated. Turbines were washed with sterile hard water used to assess the residual bacterial loads (expressed in colony forming units -cfu). Each strain was tested five times and the mean log loads were assessed. Following the European Standardization Committee, the disinfectant activity was evaluated as mean log load reduction, that is, the difference between the mean log load detected on the control-turbines and the mean log load detected on the test turbines. RESULTS: Mean bacterial loads detected on the control-turbines ranged between 105-107 cfu. The mean log load reductions resulted 7.5 log cfu for S. aureus, E. faecalis, P. aeruginosa, 6.3 for C. albicans, 5.4 for L. pneumophila, 5.3 for M. chelonae, 2.9 for B. clausii spores. CONCLUSIONS: DUW disinfection with H(2)O(2)-Ag(+) could help minimize the risk that planktonic pathogens are spread to patients during dental treatment. PMID- 26835794 TI - Biological hazards and healthcare-associated infections in Italian healthcare facilities: some considerations on inspections and accountability. AB - Healthcare-associated infections are a major clinical and public health problem that involve, in a variety of ways, healthcare professionals, hospital administrators and, above all, patients. In Italy, the incidence of infectious complications generally varies from 5-10% (hospitalized patients) to 1% (home care patients); 5-10% of such infections manifest epidemically, and infections caused by antibiotic-resistant microorganisms are becoming more and more common, with a mortality rate of 20-30%. Moreover, any "preventable deaths or serious injuries" attributable to a (concrete) causality resulting from a breach of rules, laws and regulations, as well as imprudence, incompetence or negligence by the operators will determine a possibility of a penal prosecution for manslaughter or grievous bodily harm, and also generate expenses for civil procedures and insurance compensation. The adoption of company policies covering appropriate risk assessment, epidemiological monitoring, implementation of guidelines, procedures and protocols, activity of the Hospital Infections Committee and proper communication between managers and facilities, training of healthcare personnel and medical surveillance of employees can help reduce the adverse phenomena of healthcare-associated infections. PMID- 26835795 TI - From the risk analysis to the development of interventions and training for the prevention and control of healthcare associated infections. The experience of G. Pini Orthopedic Institute. AB - BACKGROUND: Health-care associated infections (HAIs) represents a phenomenon of central importance all over Europe. Every year 4,5 millions cases are detected in European Union, with 37.000 related deaths. Surgical-site infections (SSIs) are one of the most common HAIs, that are associated with an increased length of stay, re-operation rate, intensive care admissions rate, and higher mortality rate. METHODS: G. Pini Orthopedics Institute implemented in the last two years a multimodal strategy for controlling and preventing HAIs, in particular for SSIs. RESULTS: This paper describes the prevention's strategies adopted for prevention of HAIs, at G. Pini Orthopedic Institute. CONCLUSIONS: Our findings show that application of a multi modal promotion strategy was associated with an improvement in HAI prevention. PMID- 26835796 TI - Cross-sectional study on knowledge of health care workers about Ebola Virus Disease and its prevention: a pilot study in two hospitals in Rome (Italy). AB - OBJECTIVES: To carry out a pilot study aimed: a) to define and validate a method to evaluate Health Care Workers' (HCWs') knowledge about Ebola virus disease (EVD); b) to verify if the specific training on EVD followed in Emergency Units is associated to a significant difference in knowledge. METHODS: A cross sectional study was carried out using an "ad hoc" questionnaire. It included 20 statements true/false, divided into three areas: risk of transmission (T); prevention and personal protection (PPP); environmental prevention (EP). The targets were the HCWs of Emergency Unit (trained) and Internal Medicine Units (control) of two hospitals in Rome (A and B). Internal consistency was evaluated using KR-20 coefficient. A proportion of 14/20 (70%) correct answers was considered acceptable. Mean scores and acceptable scores were compared using t Student test and chi-squared test respectively. A logistic regression was fitted to identify independent factors associated with acceptable knowledge level for the whole questionnaire and each area. RESULTS: 237 HCWs were included in the pilot study, with a participation percentage of 89.1%. The reliability coefficient (KR-20) was 0.6 for the entire 20-item questionnaire. Overall proportion of respondents with acceptable score was 32.9%; the highest proportion (61.1%) was found in trained HCWs (p<0.02). Factors associated with an acceptable knowledge were: belonging to hospital A (p<0.001) and having been trained on EVD (p=0.03). Stratifying by area, the variables significantly related to an acceptable score were: for PPP area younger HCWs (p<0.01) and nurses (p<0.01); for EP area, belonging to hospital A (p<0.01) and to Internal Medicine Unit (p=0.02). CONCLUSIONS: The high compliance and completeness of the responses indicate the validity of the method of administration adopted. In the investigated hospitals the specific training on EVD determined a significant overall improvement in knowledge. It will be appropriate to extend the study to other hospitals around the Country to evaluate the true effectiveness of the training in a larger sample of hospitals. PMID- 26835798 TI - Hygienic and sanitary requirements of gyms in force in Italy: national issues and analysis of regional regulations. AB - In recent years, the awareness of the importance of physical activity for human health is growing, as people practicing it; the number of gyms has also substantially increased. Currently, in Italy there is not a consistent regulation regarding hygienic and sanitary requirements of gyms. Several Italian regions issued laws about this topic. The authors analyse the standards required by the Italian Olympic Committee (CONI) and the regional laws, highlighting the numerous issues, among which the possible location of gyms in semi-basements and basements. They eventually call for a national regulation that should clearly transpose the hygienic and sanitary requirements of gyms into a satisfactory rule of law. PMID- 26835799 TI - The changing therapeutic armamentarium for patients with type 1 diabetes. AB - PURPOSE OF REVIEW: This article evaluates the role of Sodium glucose co transporter-2 (SGLT-2) inhibitor and Glucagon-like peptide-1 receptor agonist's (GLP-1 RA's)s in the treatment of type 1 diabetes (T1D). RECENT FINDINGS: Both agents help to produce a small reduction in HbA1C levels with accompanying weight loss. Submaximal doses of SGLT-2 inhibitors may reduce the risk for hypoglycemia as well as limit glycemic variability. However, SGLT-2 inhibitors appear to increase rates of ketone body production and diabetic ketoacidosis, and therefore must only be used in the setting of appropriate risk mitigation. GLP-1 RA's increased the risk for hypoglycemia in the largest clinical trial done to date (with a small fall in A1C), which lead to a cessation of the development of liraglutide as a treatment for T1D. SUMMARY: Off-label use of medications designed for individuals with type 2 diabetes in people with T1D has potential benefits as well as risks. If using an SGLT-2 inhibitor or a GLP-1 RA, it is important to have an informed, educated patient and follow a specific protocol. In the case of SGLT-2 inhibitors, clinical trials should help define how to use these agents more safely and effectively in T1D. PMID- 26835801 TI - One-Pot Synthesis of Highly Substituted Nicotinic Acid Derivatives Based on a Formylation Strategy of Enamino Keto Esters. AB - A facile one-pot synthesis of 4-chloro or 4-bromonicotinic acid esters with optional 2- and 2,5-disubstitution on the pyridine ring has been developed from easily accessible enamino keto esters by a formylation followed by in situ intramolecular cyclization strategy under optimized Vilsmeier reaction conditions. The effect of the substituents on the beta-carbon and the nature of the keto functionality were explored in detail to understand the mechanism of pyridine ring formation under the described conditions. PMID- 26835797 TI - Proceedings of the Consensus Day Meeting: Implications for Rotavirus Vaccination in the 2014 Apulian Lifetime Immunization Schedule. Foggia, 17 April 2015. AB - Recommendations for vaccination against rotavirus (RV) were issued in Apulia in 2006; the vaccine was free of charge to children who entered day care or nursery school by 1 year of age or those affected by chronic diseases for which diarrhea caused by rotavirus can increase the risk of complications and hospitalization. In 2014, vaccination became available to all healthy children with only a copayment. However, there has not been a significant increase in vaccination coverage. On April 17, 2015, Apulian public health physicians and paediatricians met to share strategies to promote the RV vaccine indications provided in the regional immunization schedule. During the meeting, presentation of data reports were interspersed with discussions that were led with a "bottom-up" approach. The discussants responded to pre-planned questions raised by the participants and encouraged by the discussion. PMID- 26835802 TI - Handbook of Home Healthcare Administration. PMID- 26835804 TI - Comorbid Depression and Diabetic Foot Ulcers. AB - In the United States, 9.3% of the population, or 29.1 million people have diabetes, and depression affects 20% to 40% of these individuals. Diabetic foot ulcers are a common and serious complication of diabetes and one of the most costly. It is estimated that 2% to 3% of persons with diabetes will develop diabetic foot ulcers each year. There is an association between depression and the development of diabetic foot ulcers. The estimated costs associated with managing diabetes, depression, and diabetic foot ulcers place a substantial burden on the U.S. healthcare system and society. Patients should be screened and evaluated by professionals qualified in the diagnosis and management of depression and diabetic foot ulcers. To be effective, an interprofessional approach that includes the patient and significant others should be used. PMID- 26835800 TI - Adult development and quality of life of transgender and gender nonconforming people. AB - PURPOSE OF REVIEW: Research on the health of transgender and gender nonconforming people has been limited with most of the work focusing on transition-related care and HIV. The present review summarizes research to date on the overall development and quality of life of transgender and gender nonconforming adults, and makes recommendations for future research. RECENT FINDINGS: Pervasive stigma and discrimination attached to gender nonconformity affect the health of transgender people across the lifespan, particularly when it comes to mental health and well-being. Despite the related challenges, transgender and gender nonconforming people may develop resilience over time. Social support and affirmation of gender identity play herein a critical role. Although there is a growing awareness of diversity in gender identity and expression among this population, a comprehensive understanding of biopsychosocial development beyond the gender binary and beyond transition is lacking. SUMMARY: Greater visibility of transgender people in society has revealed the need to understand and promote their health and quality of life broadly, including but not limited to gender dysphoria and HIV. This means addressing their needs in context of their families and communities, sexual and reproductive health, and successful aging. Research is needed to better understand what factors are associated with resilience and how it can be effectively promoted. PMID- 26835805 TI - Fall Prevention for Older Adults Receiving Home Healthcare. AB - Falls pose a significant risk for community-dwelling older adults. Fall-related injuries increase healthcare costs related to hospitalization, diagnostic procedures, and/or surgeries. This article describes a quality improvement project to reduce falls in older adults receiving home healthcare services. The fall prevention program incorporated best practices for fall reduction, including fall risk assessment, medication review/management, home hazard and safety assessment, staff and patient fall prevention education, and an individualized home-based exercise program. The program was implemented and evaluated during a 6 month time frame. Fewer falls occurred post implementation of the falls prevention program with no major injuries. PMID- 26835806 TI - Implementing Home Health Standards in Clinical Practice. AB - In 1986, the American Nurses Association (ANA) published the first Standards of Home Health Practice. Revised in 1992 and expanded in 1999 to become Home Health Nursing: Scope and Standards of Practice, it was revised in 2008 and again in 2014. In the 2014 edition, there are 6 standards of home healthcare nursing practice and 10 standards of professional performance for home healthcare nursing. The focus of this article is to describe the home healthcare standards and to provide guidance for implementation in clinical practice. It is strongly encouraged that home healthcare administrators, educators, and staff obtain a copy of the standards and fully read this essential home healthcare resource. PMID- 26835807 TI - Effective Teaching-Learning Strategies for the Omaha System. AB - Home healthcare clinicians can benefit from the use of interprofessional standardized terminologies to more efficiently document and assess patient problems, describe and present clinician interventions, and measure the outcomes of care. The Omaha System is a research-based, comprehensive standardized terminology that can enable users to describe and measure the impact of nursing and healthcare services on patient care and outcomes. In this article, we (1) describe effective strategies for teaching the Omaha System to home healthcare agency staff, and (2) illustrate those strategies' effectiveness by presenting an example from an Omaha System Basic Workshop conducted in 2015. The 12 participants included home healthcare nursing administrators and clinicians, software developers from several companies, nursing educators, and nursing researchers. The role-playing and unfolding case studies that we report here represent teaching strategies that can provide opportunities for home healthcare users to practice using the Omaha System. Quantitative evaluation consisted of comparing the participants' pretest and posttest scores on the survey. Qualitative evaluation involved analyzing participants' feedback and comments on a form distributed at the end of the workshop. Participants found the workshop beneficial in improving their understanding of the Omaha System and its application to their practice. PMID- 26835808 TI - Physical Activity Outcomes of Nurse-Delivered Lifestyle Interventions. AB - Promotion of physical activity has been a public health priority for decades. Over two million home healthcare nurses are at the front line to deliver effective health education and health promotion interventions in the United States. The purpose of this systematic review is to examine the effectiveness of nurse-delivered lifestyle physical interventions on physical activity outcomes conducted in home settings. Computerized database and ancestry search strategies located distinct intervention trials between 1990 and 2015. A total of eight quantitative studies were reviewed. Four of the eight studies were randomized control trials and four studies used an uncontrolled pretest-posttest design. The eight studies represented a total of 1,221 participants with mean ages from 43 to 81. Study sample sizes ranged from 16 to 504. Seven of the eight studies demonstrated modest effect of nurse-delivered home-based interventions on physical activity behaviors. Home-based physical activity promotion was most often incorporated into secondary prevention of postacute diseases, chronic disease management, or disease prevention/health promotion. Findings indicate that nurse-delivered home-based physical activity promotion show overall effectiveness in general adult populations. Possible effective intervention domains were also discussed in this review to guide future home-based health promotion. More large randomized controlled trials with longer study/follow-up periods and studies with cost-effectiveness data are warranted in future research. PMID- 26835809 TI - U-200 Humalog Insulin Now Available in United States. PMID- 26835810 TI - Auvi-Q Post Injection Ticking Sound. PMID- 26835811 TI - Frequency for Changing Long-Term Indwelling Urethral Catheters. PMID- 26835812 TI - A Day in the Life of a Home Healthcare Aide. PMID- 26835813 TI - Debunking Hospice Myths. PMID- 26835814 TI - The Legislative Priority of Home Healthcare and Quality. PMID- 26835815 TI - Reducing Readmissions Through a Targeted Geriatric Pharmacy Program. PMID- 26835816 TI - The History of the International Home Care Organization. PMID- 26835817 TI - Home Care Staffing and Patient Satisfaction. PMID- 26835819 TI - New Lanthanide Mixed-Valent Vanadium(III/IV) Oxosilicates, Ln4V(5-x)Zn(x)Si4O22 (Ln = La, Ce, Pr, and Nd), Crystallizing in a Quasi Two-Dimensional Rutile-Based Structure. AB - A family of lanthanide mixed-valent vanadium(III/IV) oxosilicates Ln4V(5 x)Zn(x)Si4O22 (Ln = La, Ce, Pr, and Nd) was synthesized as high-quality single crystals via a high-temperature molten salt method. An in situ reduction of V(V) to V(III/IV) as well as of Ce(IV) to Ce(III) was achieved utilizing Zn metal as the reducing agent, some of which is incorporated into the crystal structure. Ce4V(4.77)Zn(0.23)Si4O22, to the best of our knowledge, is the first example of a cerium-containing mixed-valent vanadium silicate. The crystal structures were determined by single-crystal X-ray diffraction, and the four isostructural oxosilicates were determined to crystallize in the chevkinite-structure type in the monoclinic space group I2/a. The unit cells of the Ln4V(5-x)Zn(x)Si4O22 (Ln = La, Ce, Pr, and Nd) series are related to the reported C2/m phases Ln4V5Si4O22 (Ln = La, Pr, and Nd) by a doubling of the c-axis and a loss of a mirror plane. The three-dimensional crystal structure consist of two-dimensional rutile-based vanadium oxide and lanthanide oxide layers linked via Si2O7 groups. The temperature dependence of the magnetic susceptibility of these compounds was measured, and only the Nd analogue exhibited a magnetic transition at 5 K; all samples displayed a discontinuity or deviation from linearity at ca. 130-150 K. PMID- 26835820 TI - Practicality of the Lower Extremity Lymphedema Index: Lymphedema Index Versus Volumetry-Based Evaluations for Body-Type-Corrected Lower Extremity Volume Evaluation. AB - BACKGROUND: Volume measurement is one of the most commonly used methods for lower extremity lymphedema (LEL) evaluation because of its objectivity. However, volume comparison between different patients with different body types may be inappropriate because body-type difference seems to significantly affect leg volume (LV). METHODS: Twenty-seven nonedematous legs of 27 unilateral LEL patients were evaluated. The LEL index was calculated using circumferences and body mass index (BMI), and LV was calculated using a summed truncated cone model. The BMI of the examinees was classified into 3 groups: low BMI (BMI < 20), middle BMI (BMI, 20-25), and high BMI (BMI > 25). The LEL index, LV, LV divided by body surface area (LV/BSA), and LV divided by BMI (LV/BMI) were compared with the corresponding BMI groups. RESULTS: The mean (SD) LEL index was 218.6 (12.9), and the mean (SD) LV was 4081.3 (835.6) mL. Between the low-, middle-, and high-BMI groups, there were no significant differences in the LEL index [223.2 (11.4), 217.8 (13.3), and 214.6 (14.2), P > 0.5] or in LV/BMI [185.5 (9.2), 179.3 (11.3), and 175.7 (15.8) mL per kg/m, P > 0.3], whereas significant differences were seen in LV [3484.9 (366.0), 3924.4 (342.5), and 5387.7 (1038.4) mL, P < 0.001) and in LV/BSA [2404.3 (236.6), 2539.2 (141.4), and 3106.0 (460.8) mL/m, P < 0.001]. CONCLUSIONS: The LEL index and LV/BMI stayed constant regardless of BMI, whereas LV and LV/BSA significantly increased with increase in BMI. With simplicity of calculation, the LEL index would allow more practical body-type-corrected LV evaluation compared with volumetry-based evaluations. PMID- 26835822 TI - The Incidence of Ocular Injuries in Isolated Orbital Fractures. AB - BACKGROUND: Prompt identification of significant ocular injuries in patients who sustain an orbital fracture is important to prevent any potential long-term visual sequelae. The true incidence of these injuries has not been determined, however. As a consequence, most surgeons choose to have all patients evaluated by an ophthalmologist. The objective of this study was to conclusively identify the incidence of significant ocular injuries in patients with isolated orbital fractures and to determine their predictors to guide more efficient patient care. METHODS: A prospective cohort study powered to detect a 15% incidence of ocular injuries was designed. All patients presenting to our center with computed tomography findings of an isolated orbital fracture were included and evaluated by plastic surgery and ophthalmology services. Patients were followed up for a minimum of 1 week to identify any delayed injuries. RESULTS: Eighty patients were enrolled from 2012 to 2014. There were 46 men and 34 women with a mean age of 42.8 years. Assault was the most common mechanism of injury. There were 8 ocular injuries (10%): ruptured globe (1), uveal prolapse (1), retrobulbar hemorrhage (2), hyphema (2), hemorrhagic glaucoma with hyphema (1), and scleral tear (1). Predictors for significant ocular injuries were grossly abnormal visual acuity and abnormal pupillary reactivity of the affected eye. CONCLUSIONS: The incidence of significant ocular injuries in isolated orbital fractures is lower than previously reported. Patients presenting with grossly abnormal visual acuity or abnormal pupillary reactivity are at high risk and should receive prompt ophthalmology service evaluation. PMID- 26835821 TI - Risk Factor Analysis for Mastectomy Skin Flap Necrosis: Implications for Intraoperative Vascular Analysis. AB - INTRODUCTION: Skin flap necrosis after mastectomy can be a devastating complication significantly affecting patient outcomes. Routine vascular analysis (fluorescein or laser angiography) of mastectomy skin flaps in all patients has been advocated but is of questionable cost-effectiveness. The purpose of this study was to identify the incidence and causative risk factors for mastectomy skin flap necrosis and thereby calculate the fiscal reality of intraoperative vascular screening. METHODS: This is an institutional review board-approved retrospective study of all patients from 2007 to 2013 who underwent mastectomy related to breast cancer. Skin flap necrosis was defined as major if it necessitated return to the operating room. Data analysis was done for determination of causative factors of necrosis, including age, body mass index, smoking, previous irradiation, coronary artery disease, chronic obstructive pulmonary disorder, hypertension, gastroesophageal reflux disease, hyperlipidemia, obstructive sleep apnea, asthma, diabetes, thyroid disease, history of lumpectomy, and breast reduction or augmentation. During this time, intraoperative vascular screening was not done. RESULTS: Five hundred eighty-one patients underwent 616 mastectomies with a total of 34 necrotic events (5.5%)-16 major and 18 minor. Analyses via Student t tests, univariate analyses, chi testing, and logistic regression showed that history of smoking was the only patient factor associated with postoperative necrosis (P = 0.008). More frequently represented in the necrosis group, but without statistical significance, are previous lumpectomy (P = 0.069) and immediate reconstruction (P = 0.078).For the entire study period, the actual cost to the hospital for major necrotic events was $7,123.10 or $445.19 for each of the 16 major necrotic events and $209.50 for all 34 necrotic events. Per-patient cost-effective screening would need to be less than $11.54 for all patients, $100.33 for highest risk patients (smokers), and $21.65 for highest risk patients (smokers, previous lumpectomy, and immediate reconstruction). CONCLUSIONS: Vascular screening other than clinical judgment of all patients is not cost effective. However, intraoperative vascular evaluation of high-risk patients is recommended before reconstruction and/or closure. These financial data that incorporate true costs and revenue can guide the use of newer, more expensive technology such as laser angiography and can be extrapolated to other institutions. PMID- 26835823 TI - Dual Nerve Transfers for Restoration of Shoulder Function After Brachial Plexus Avulsion Injury. AB - The purpose of this study was to investigate the effectiveness of shoulder function restoration by dual nerve transfers, spinal accessory nerve to the suprascapular nerve and 2 intercostal nerves to the anterior branch of the axillary nerve, in patients with shoulder paralysis that resulted from brachial plexus avulsion injury. It was a retrospective analysis to assess the impact of a variety of factors on reanimation of shoulder functions with dual nerve transfers. A total of 19 patients were included in this study. Most of these patients sustained avulsions of C5, C6, and C7 nerve roots (16 patients). Three of them had avulsions of C5 and C6 roots only. Through a posterior approach, direct coaptation of the intercostal nerves and the anterior branch of the axillary nerve was performed, along with accessory nerve transfer to the suprascapular nerve. Satisfactory shoulder function recovery (93.83 degrees of shoulder abduction and 54.00 degrees of external rotation on average) was achieved after a 62-month follow-up. This dual nerve transfer procedure provided us with a reliable and effective method for shoulder function reconstruction after brachial plexus root avulsion, especially C5/C6/C7 avulsion. The level of evidence is therapeutic IV. PMID- 26835824 TI - Outbreak of Rapidly Growing Nontuberculous Mycobacteria Among Patients Undergoing Cosmetic Surgery in the Dominican Republic. AB - Rapidly growing nontuberculous mycobacteria (RG-NTM), which can contaminate inadequately sterilized medical instruments, have been known to cause serious postsurgical skin and soft tissue infections that often are characterized by a prolonged incubation period and a disfiguring clinical course. Historically, these infections have been associated with surgical procedures performed outside the United States. The Centers for Disease Control and Prevention recently reported an outbreak of RG-NTM infections among women who underwent cosmetic surgery in the Dominican Republic. Because of the large Dominican American community in upper Manhattan, we have recently observed a number of these cases at NewYork-Presbyterian Hospital/Columbia University Medical Center. We highlight the case of a 55-year-old woman who developed a postsurgical RG-NTM infection after bilateral breast reduction in the Dominican Republic; she experienced progressive deformity of her left breast until the causative pathogen was identified 20 months after her initial surgery. To assist in the timely diagnosis and treatment of these infections, we aim to promote greater awareness among physicians who are likely to encounter such patients. We present the pathologic findings of a review of 7 cases of RG-NTM infections seen at NewYork-Presbyterian Hospital/Columbia University Medical Center and discuss the diagnostic and therapeutic challenges associated with these infections, such as prolonged incubation periods, the need for acid-fast stains and mycobacterial cultures, and the combination of surgical therapy and lengthy antibiotic courses that are often required for treatment. PMID- 26835825 TI - Repeat Double-Opposing Z-Plasty for the Management of Persistent Velopharyngeal Insufficiency. AB - BACKGROUND: Persistent velopharyngeal insufficiency occurrence after double opposing Z-plasty has been treated with either posterior pharyngeal flap or sphincteroplasty. Both these methods can be accompanied by mild discomfort, such as mouth breathing and hyponasal resonance, and can lead to severe complications, such as sleep apnea and upper airway compromise. The purpose of this study was to review the efficacy of repeat double-opposing Z-plasty for the management of persistent velopharyngeal insufficiency in patients who received a prior surgical intervention by double-opposing Z-plasty. METHODS: All patients who were treated by repeat double-opposing Z-plasty between January 2000 and December 2014 were reviewed. Patient demographics, cleft type, surgical technique, and complications, such as wound dehiscence, infection, fistula, and upper airway obstruction, were evaluated. Preoperative and postoperative speech evaluations were reviewed for comparison. RESULTS: Fourteen patients underwent repeat double opposing Z-plasty, with an average follow-up of 34 months. There was no complication including wound dehiscence, flap necrosis, fistula, or upper airway compromise. Velopharyngeal competence (resonance, nasal emission, intraoral pressure, social/personal problems) was significantly improved postoperatively (P < 0.05). Only 1 patient required posterior pharyngeal flap for persistent velopharyngeal insufficiency. CONCLUSIONS: Repeat double-opposing Z-plasty is an effective and safe surgical strategy for the management of persistent velopharyngeal insufficiency, in patients who received a prior surgical intervention by double-opposing Z-plasty. This strategy allows speech improvement and reduces the risk of postoperative upper airway compromise. PMID- 26835826 TI - Reduction Gonioplasty: Bone Regeneration and Soft Tissue Response. AB - BACKGROUND: Reduction gonioplasty is frequently used to achieve an oval-shaped face in Asia. However, the soft tissue response and bone regeneration of reduction gonioplasty which are keys to the outcome are still unclear. The aim of this study is to evaluate the effects of bone regeneration on facial width and the soft tissue response of reduction gonioplasty. METHODS: We retrospectively reviewed patients who underwent reduction gonioplasty from 2009 to 2013. A high speed rotary cutting bur without a water coolant was routinely used from the new gonial point to the inferior mandibular rim under the second premolar, whereas the elongated osteotomy line (mandibular-chin body osteotomy) was performed with a reciprocating saw. Forty-nine patients with preoperative, immediate postoperative, and 12-month postoperative frontal cephalograms were included in our study. Mandible and soft tissue profiles were measured on cephalograms. RESULTS: Bone regeneration in high-speed rotary cutting bur ostectomy region was 0.79 +/- 1.76 mm (1 cm above Go-Go), -0.75 +/- 1.46 mm (Go-Go, bigonial line), and -0.77 +/- 2.10 mm (1 cm below Go-Go), whereas 0.07 +/- 1.79 mm (2 cm below Go Go) in ostectomy region performed by reciprocating saw. The soft tissue response ratios were 76.72 +/- 30.70% (Go-Go), 108.8 +/- 54.11% (1 cm below Go-Go), and 155.9 +/- 66.82% (2 cm below Go-Go). CONCLUSIONS: Bone regeneration does not lead to an increase in facial width after reduction gonioplasty with our technique, and the use of a high-speed rotary cutting bur without a water coolant decreases bone regeneration. The soft tissue response ratio is higher in the anterior mandible, and the outcome of reduction gonioplasty is a sharper lower face with a full cheek. Reduction gonioplasty is an effective and predictable lower face reshaping surgery. PMID- 26835827 TI - Course Review: North East Microsurgery Training Course and Workshop: A New Two Day Microsurgery Course for Trainees in Plastic Surgery, Otolaryngology and Oral and Maxillofacial Surgery. AB - Undertaking a microsurgical course is a key adjunct to trainee development in plastic surgery, otololaryngology and oral and maxillofacial surgery. Traditionally, these courses last approximately 5 days and can cost upward of US $2000 (L1500).The North East Microsurgery Training Course and Workshop is a new 2 day course costing just US $760 (L500). This course was set up in 2015 by reconstructive microsurgeon Mr Maniram Ragbir at the Freeman Hospital in Newcastle, England.The aim of the course is provide maximum hands-on experience in microsurgery for surgical trainees interested in relevant specialties under close supervision of experienced consultant faculty. It is a must for younger trainees learning microsurgery or more senior trainees looking to improve their skills. PMID- 26835828 TI - Tripaddle Posterior Interosseous Artery Flap Design for 3-Finger Defects: An Evaluation of 3 Surgical Approaches. AB - INTRODUCTION: The tripaddle posterior interosseous artery (PIA) flap can be used for multifinger defect resurfacing, but interpatient variations in perforator distribution remain an ongoing challenge when using this approach. This study aims to evaluate the efficacy of 3 different tripaddle PIA perforator flap designs according to the PIA perforator distribution for the repair of 3-finger defects. METHODS: In accordance with the size of the 3-finger defects and the position of the perforators, a tripaddle flap was designed on the multiple perforators of the descending branch of the PIA in the distal two thirds of the forearm. Patients received 1 of 3 distinct tripaddle PIA perforator flap designs based on perforator distributions of the PIA. RESULTS: Three cases of 3-finger defects were repaired with type A trefoil-shaped tripaddle flaps, whereas 4 cases were repaired with type B modified trefoil-shaped tripaddle flaps, and the other 3 cases were repaired with type C chain-shaped tripaddle flaps. All flaps survived except 2 paddles with tip necrosis. After 9.1 months of mean follow-up, 9 of the 10 cases demonstrated satisfactory cosmetic appearance, whereas the last case required a debulking procedure in the second stage. CONCLUSIONS: The free tripaddle PIA perforator flap is an effective option for repairing 3-finger skin defects. Various flap designs based on the PIA perforator distribution allow for more individualized treatment approaches. PMID- 26835830 TI - Madelung Disease Affecting Scrotal Region. AB - Madelung disease is an uncommon disease characterized by large subcutaneous adipose masses. Mediterranean countries show higher disease incidence. We review the current concepts concerning this pathology, including etiology, diagnosis, and treatment. Madelung disease usually affects the upper half of the body, but we describe a patient with scrotal lipomas. As this location is rare, we review the cases found in literature, as well as the specific nuances regarding local symptoms and treatment. PMID- 26835829 TI - Management of Mycobacterium abscessus Infection After Medical Tourism in Cosmetic Surgery and a Review of Literature. AB - INTRODUCTION: Despite news reports, Food and Drug Administration disclaimers, and warnings from US plastic surgeons against the perils of cosmetic tourism, patients continue to seek care abroad and often present with infectious complications. Recent reports of Mycobacterium abscessus surgical site infection (SSI) is of particularly concern and its management, particularly surgical intervention, has been poorly documented. METHODS: A retrospective review of 2 sisters who presented with M. abscessus SSI after cosmetic surgery in the Dominican Republic was performed. A comprehensive review of the literature was conducted to unveil similar cases after cosmetic tourism. RESULTS: Both patients presented four months after index operation after definitive diagnoses have been reached. They were counselled to undergo immediate, aggressive debridement and antibiotic therapy. Although 1 patient agreed, the other patient opted for local wound care and oral antibiotics in hopes to avoid reoperation. When unsuccessful, she agreed to the initial plan which led to rapid convalescence of her infection. However, aesthetic result was far inferior to the first patient. Review of literature revealed 14 women with an average age of 40 years (range, 19-60 years). Most frequent cosmetic operations that resulted in M. abscessus SSI were abdominoplasty (41%), liposuction (27%), breast augmentation (14%), breast reduction (9%), and rejuvenation surgery (9%). Surgical interventions were performed in all cases except one. Antibiotic therapies focused on macrolides, particularly clarithromycin or azithromycin, with average time to complete recovery of 8 months (range, 2-22 months). CONCLUSIONS: The 2 cases highlighted the importance of multidisciplinary approach of early aggressive surgical intervention and long-term intravenous antibiotics in treating M. abscessus SSI that is highly prevalent among those returning from medical tourism in cosmetic surgery. PMID- 26835831 TI - The Value of Multidetector Row Computed Tomography Angiography for Preoperative Planning of Freestyle Pedicled Perforator Flaps. AB - BACKGROUND: Because the course and territory of perforators are different in each region, careful preoperative planning to identify the proper perforators can be critical to ensure a successful dissection of a freestyle pedicled perforator flap. In this study, our first experience for preoperative perforator mapping of a freestyle pedicled perforator flap using multidetector row computed tomography (MD-CT) angiography is presented. METHODS: Twelve patients were planned to undergo various soft-tissue reconstructions with freestyle pedicled perforator flaps. They were evaluated with preoperative MD-CT angiography. The OsiriX for mac software was used to process the data obtained from MD-CT angiography. The available images from MD-CT angiography were analyzed to determine where the proper perforators were located for preoperative planning of a freestyle pedicled perforator flap. Through the MD-CT angiography, the optimal perforators were mapped and a reliable flap design could be made so that the flap was elevated more safely and perfectly to cover an adjacent soft-tissue defect. RESULTS: In all 12 patients, each flap was elevated successfully based on the perforators mapped preoperatively with MD-CT angiography. A total of 27 perforators (1-3 perforators per flap) were identified by MD-CT angiography in 12 patients and later confirmed during the flap dissection (sensitivity, 100%). CONCLUSIONS: The MD-CT angiography can be a new but very effective imaging modality for preoperative planning of a freestyle pedicled perforator flap surgery. It allows surgeons to accurately select the most appropriate perforators with the shortest intramuscular or suprafascial course preoperatively leading to safer and easier flap dissection. PMID- 26835832 TI - Dynamic Prognostication Using Conditional Recurrence and Progression Estimates for Patients with Nonmuscle Invasive Bladder Cancer. AB - PURPOSE: Conditional estimates provide a dynamic prediction of outcomes but to our knowledge there are no data on nonmuscle invasive bladder cancer. We assessed changes in conditional recurrence and progression rates after transurethral resection of the bladder and explored the prognostic impact of established factors and risk groups with time. MATERIALS AND METHODS: We retrospectively analyzed data on 1,292 consecutive patients with newly diagnosed Ta/T1 bladder cancer who underwent transurethral resection of the bladder. Study end points were time to first recurrence and time to progression. RESULTS: The 2-year recurrence rate at baseline was 36%, which improved as a function of the time that patients were free of disease recurrence. After 6, 12, 24, 36 and 48 months the 2-year conditional recurrence rate improved to 31% (14% improvement vs baseline), 22% (39% improvement), 16% (56% improvement), 13% (64% improvement) and 11% (69% improvement), respectively. Comparably, conditional progression rates improved with increasing followup, although relative differences were less distinct. The prognostic impact of established factors and nonmuscle invasive bladder cancer risk groups progressively decreased with time and finally disappeared. However, bacillus Calmette-Guerin had a protective effect on progression even after 3 years. We provide tables with dynamic prognostic information at all analyzed time points. CONCLUSIONS: In patients with primary Ta/T1 bladder cancer recurrence and progression rates improve with time. The prognostic impact of established factors and risk groups decreases and finally disappears. The effect of bacillus Calmette-Guerin on progression is long lasting. Conditional outcome estimates may improve patient counseling and individualize surveillance planning. PMID- 26835833 TI - Diagnosing Testicular Torsion before Urological Consultation and Imaging: Validation of the TWIST Score. AB - PURPOSE: The TWIST (Testicular Workup for Ischemia and Suspected Torsion) score uses urological history and physical examination to assess risk of testis torsion. Parameters include testis swelling (2 points), hard testis (2), absent cremasteric reflex (1), nausea/vomiting (1) and high riding testis (1). While TWIST has been validated when scored by urologists, its diagnostic accuracy among nonurological providers is unknown. We assessed the usefulness of the TWIST score when determined by nonurological nonphysician providers, mirroring emergency room evaluation of acute scrotal pain. MATERIALS AND METHODS: Children with unilateral acute scrotum were prospectively enrolled in a National Institutes of Health clinical trial. After undergoing basic history and physical examination training, emergency medical technicians calculated TWIST score and determined Tanner stage per pictorial diagram. Clinical torsion was confirmed by surgical exploration. All data were captured into REDCapTM and ROC curves were used to evaluate the diagnostic usefulness of TWIST. RESULTS: Of 128 patients (mean age 11.3 years) 44 (13.0 years) had torsion. TWIST score cutoff values of 0 and 6 derived from ROC analysis identified 31 high, 57 intermediate and 40 low risk cases (positive predictive value 93.5%, negative predictive value 100%). CONCLUSIONS: TWIST score assessed by nonurologists, such as emergency medical technicians, is accurate. Low risk patients do not require ultrasound to rule out torsion. High risk patients can proceed directly to surgery, with more than 50% avoiding ultrasound. In the future emergency medical technicians and/or emergency room triage personnel may be able to calculate TWIST score to guide radiological evaluation and immediate surgical intervention at initial assessment long before urological consultation. PMID- 26835834 TI - Evolution of testes characteristics in entire and immunocastrated male pigs from 30 to 120 kg live weight as assessed by computed tomography with perspective on boar taint. AB - The present study addressed (1) the levels of boar taint compounds in entire (EM) and immunocastrated (IM) male pigs during their growth, (2) the evolution of testes volume and density and (3) the relationship between physical characteristics of the testes and boar taint compounds. For that purpose 24 EM and 20 IM pigs were CT scanned at several body weights (TBW). After each scanning a subsample of pigs was slaughtered, and subcutaneous fat was collected to determine androstenone and skatole concentration. Additional subsample (n=4/sex) was CT scanned 13 days after the second vaccination (V2). Testes density changes with growth, is different in EM and IM, but is not a reliable marker of the level of boar taint compounds. On the other hand, testes to body volume ratio is a better predictor for androstenone and could provide a good tool at slaughter plants to detect immunocastrated pigs with high boar taint compounds. PMID- 26835835 TI - Multivariate regression analysis applied to the calibration of equipment used in pig meat classification in Romania. AB - This paper highlights the statistical methodology used in a dissection experiment carried out in Romania to calibrate and standardize two classification devices, OptiGrade PRO (OGP) and Fat-o-Meat'er (FOM). One hundred forty-five carcasses were measured using the two probes and dissected according to the European reference method. To derive prediction formulas for each device, multiple linear regression analysis was performed on the relationship between the reference lean meat percentage and the back fat and muscle thicknesses, using the ordinary least squares technique. The root mean squared error of prediction calculated using the leave-one-out cross validation met European Commission (EC) requirements. The application of the new prediction equations reduced the gap between the lean meat percentage measured with the OGP and FOM from 2.43% (average for the period Q3/2006-Q2/2008) to 0.10% (average for the period Q3/2008-Q4/2014), providing the basis for a fair payment system for the pig producers. PMID- 26835836 TI - Comparison of ADH3 promoter with commonly used promoters for recombinant protein production in Pichia pastoris. AB - Recombinant protein production under the control of the PADH3 was compared with Pichia pastoris PAOX1 and PGAP. The single-copy-clones expressing Aspergillus niger xylanase (XylB) gene with the three different promoters were tested in shake flask and 5 L fed-batch fermentation processes. Recombinant protein production with PADH3, PAOX1 and PGAP were initiated by addition of ethanol, methanol and glucose, respectively in the culture medium. The fermentation process was carried out for 72 h at 30 degrees C, pH 5 and 30% dissolved oxygen. Extracellular protein production yield for PADH3 (3725 U/mL) was higher than for PAOX1 (2095 U/mL) and PGAP (580 U/mL) at fermentor scale under the conditions tested. These results show that the PADH3 promoter is a promising tool for large scale production of recombinant proteins and can be an alternative to the PAOX1 and PGAP. PMID- 26835837 TI - In vivo at last: Demonstrating the biological credentials and clinical potential of GM-CSF. AB - The pioneering contribution of Professor Donald Metcalf, who passed away in 2014, to the discovery and characterisation of the colony-stimulating factors (CSFs) is exemplified by a seminal contribution to Experimental Haematology by Metcalf and colleagues that detailed the in vivo actions of the newly available recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) in 1987. The results described in this publication promoted GM-CSF actions from fascinating in vitro laboratory phenomena to the recognition that this cytokine was a genuine in vivo regulator of blood cell production and function and provided significant impetus for the clinical development of GM-CSF. PMID- 26835838 TI - Design, Synthesis, and Validation of an Effective, Reusable Silicon-Based Transfer Agent for Room-Temperature Pd-Catalyzed Cross-Coupling Reactions of Aryl and Heteroaryl Chlorides with Readily Available Aryl Lithium Reagents. AB - A reusable silicon-based transfer agent (1) has been designed, synthesized, and validated for effective room-temperature palladium-catalyzed cross-coupling reactions (CCRs) of aryl and heteroaryl chlorides with readily accessible aryl lithium reagents. The crystalline, bench-stable siloxane transfer agent (1) is easily prepared via a one-step protocol. Importantly, this "green" CCR protocol circumvents prefunctionalization, isolation of organometallic cross-coupling partners, and/or stoichiometric waste aside from LiCl. DFT calculations support a sigma-bond metathesis mechanism during transmetalation and lead to insights on the importance of the CF3 groups. PMID- 26835839 TI - Evaluation of conventional imaging performance in a research whole-body CT system with a photon-counting detector array. AB - This study evaluated the conventional imaging performance of a research whole body photon-counting CT system and investigated its feasibility for imaging using clinically realistic levels of x-ray photon flux. This research system was built on the platform of a 2nd generation dual-source CT system: one source coupled to an energy integrating detector (EID) and the other coupled to a photon-counting detector (PCD). Phantom studies were conducted to measure CT number accuracy and uniformity for water, CT number energy dependency for high-Z materials, spatial resolution, noise, and contrast-to-noise ratio. The results from the EID and PCD subsystems were compared. The impact of high photon flux, such as pulse pile-up, was assessed by studying the noise-to-tube-current relationship using a neonate water phantom and high x-ray photon flux. Finally, clinical feasibility of the PCD subsystem was investigated using anthropomorphic phantoms, a cadaveric head, and a whole-body cadaver, which were scanned at dose levels equivalent to or higher than those used clinically. Phantom measurements demonstrated that the PCD subsystem provided comparable image quality to the EID subsystem, except that the PCD subsystem provided slightly better longitudinal spatial resolution and about 25% improvement in contrast-to-noise ratio for iodine. The impact of high photon flux was found to be negligible for the PCD subsystem: only subtle high-flux effects were noticed for tube currents higher than 300 mA in images of the neonate water phantom. Results of the anthropomorphic phantom and cadaver scans demonstrated comparable image quality between the EID and PCD subsystems. There were no noticeable ring, streaking, or cupping/capping artifacts in the PCD images. In addition, the PCD subsystem provided spectral information. Our experiments demonstrated that the research whole-body photon-counting CT system is capable of providing clinical image quality at clinically realistic levels of x-ray photon flux. PMID- 26835841 TI - The effects of fantastical pretend-play on the development of executive functions: An intervention study. AB - Although recent correlational studies have found a relationship between fantasy orientation (FO; i.e., a child's propensity to play in a fantastical realm) and higher order cognitive skills called executive functions (EFs), no work has addressed the causality and directionality of this relationship. The current study experimentally examined the directionality of the observed relationship between FO and EF development in preschool-aged children through an innovative play intervention employing a randomized controlled design. A sample of 110 children between the ages of 3 and 5years were randomly assigned to one of three conditions: fantastical pretend-play intervention, non-imaginative play intervention, or business-as-usual control. Results revealed that children who participated in a 5-week fantastical pretend-play intervention showed improvements in EFs, whereas children in the other two conditions did not. Within the fantastical pretend-play condition, children who were highly engaged in the play and those who were highly fantastical demonstrated the greatest gains in EFs. These data provide evidence for the equifinal relationship between fantasy oriented play and EF development, such that engaging in fantasy-oriented play may be one of many ways to directly enhance EF development. PMID- 26835842 TI - The involvement of long-term serial-order memory in reading development: A longitudinal study. AB - Recent findings suggest that Hebb repetition learning-a paradigmatic example of long-term serial-order learning-is impaired in adults with dyslexia. The current study further investigated the link between serial-order learning and reading using a longitudinal developmental design. With this aim, verbal and visual Hebb repetition learning performance and reading skills were assessed in 96 Dutch speaking children who we followed from first through second grade of primary school. We observed a positive association between order learning capacities and reading ability as well as weaker Hebb learning performance in early readers with poor reading skills even at the onset of reading instruction. Hebb learning further predicted individual differences in later (nonword) reading skills. Finally, Hebb learning was shown to explain a significant part of the variance in reading performance above and beyond phonological awareness. These findings highlight the role of serial-order memory in reading ability. PMID- 26835843 TI - Ultrafast Charge Transfer Pathways Through A Prototype Amino-Carboxylic Molecular Junction. AB - Charge transport properties of a vertically stacked organic heterojunction based on the amino-carboxylic (A-C) hydrogen bond coupling scheme are investigated by means of X-ray resonant photoemission and the core-hole clock method. We demonstrate that hydrogen bonding in molecular bilayers of benzoic acid/cysteamine (BA/CA) with an A-C coupling scheme opens a site selective pathway for ultrafast charge transport through the junction. Whereas charge transport from single BA layer directly coupled to the Au(111) is very fast and it is mediated by the phenyl group, the interposition of an anchoring layer of CA selectively hinders the delocalization of electrons from the BA phenyl group but opens a fast charge delocalization route through the BA orbitals close to the A-C bond. This evidences that hydrogen bonding established upon A-C recognition can be exploited to spatially/orbitally manipulate the charge transport properties of heteromolecular junctions. PMID- 26835844 TI - On-chip acoustophoretic isolation of microflora including S. typhimurium from raw chicken, beef and blood samples. AB - Pathogen analysis in food samples routinely involves lengthy growth-based pre enrichment and selective enrichment of food matrices to increase the ratio of pathogen to background flora. Similarly, for blood culture analysis, pathogens must be isolated and enriched from a large excess of blood cells to allow further analysis. Conventional techniques of centrifugation and filtration are cumbersome, suffer from low sample throughput, are not readily amenable to automation and carry a risk of damaging biological samples. We report on-chip acoustophoresis as a pre-analytical technique for the resolution of total microbial flora from food and blood samples. The resulting 'clarified' sample is expected to increase the performance of downstream systems for the specific detection of the pathogens. A microfluidic chip with three inlets, a central separation channel and three outlets was utilized. Samples were introduced through the side inlets, and buffer solution through the central inlet. Upon ultrasound actuation, large debris particles (10-100 MUm) from meat samples were continuously partitioned into the central buffer channel, leaving the 'clarified' outer sample streams containing both, the pathogenic cells and the background flora (ca. 1 MUm) to be collected over a 30 min operation cycle before further analysis. The system was successfully tested with Salmonella typhimurium-spiked (ca. 10(3)CFU mL(-1)) samples of chicken and minced beef, demonstrating a high level of the pathogen recovery (60-90%). When applied to S. typhimurium contaminated blood samples (10(7)CFU mL(-1)), acoustophoresis resulted in a high depletion (99.8%) of the red blood cells (RBC) which partitioned in the buffer stream, whilst sufficient numbers of the viable S. typhimurium remained in the outer channels for further analysis. These results indicate that the technology may provide a generic approach for pre-analytical sample preparation prior to integrated and automated downstream detection of bacterial pathogens. PMID- 26835845 TI - Pd(II)-Catalyzed C3-Selective Arylation of Pyridine with (Hetero)arenes. AB - Palladium catalyzed, nondirected C3-selective arylation of pyridines with arenes and heteroarenes in the presence of 1,10-phenanthroline as the ligand has been developed. The optimized conditions allow for a highly C3-selective arylation of pyridines, affording various 3,3'-bipyridines and 3-arylpyridines. PMID- 26835846 TI - (123)I-meta-iodobenzylguanidine (MIBG) cardiac scintigraphy in alpha synucleinopathies. AB - Cardiac meta-iodobenzylguanidine (MIBG) uptake on (123)I-MIBG cardiac scintigraphy is reduced in patients with Lewy body disease such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and pure autonomic failure, and has been reported to be useful for differentiating PD from other parkinsonian syndromes, as well as DLB from Alzheimer disease (AD). Postmortem studies have shown that the number of tyrosine hydroxylase (TH)-immunoreactive nerve fibers of the heart was decreased in pathologically-confirmed Lewy body disease, supporting the findings of reduced cardiac MIBG uptake in Lewy body diseases. Now, reduced cardiac MIBG uptake can be a potential biomarker for the presence of Lewy bodies in the nervous system. (123)I-MIBG cardiac scintigraphy can allow us to determine the presence of Lewy bodies. PMID- 26835848 TI - A titanium surface with nano-ordered spikes and pores enhances human dermal fibroblastic extracellular matrix production and integration of collagen fibers. AB - The acquisition of substantial dermal sealing determines the prognosis of percutaneous titanium-based medical devices or prostheses. A nano-topographic titanium surface with ordered nano-spikes and pores has been shown to induce periodontal-like connective tissue attachment and activate gingival fibroblastic functions. This in vitro study aimed to determine whether an alkali-heat (AH) treatment-created nano-topographic titanium surface could enhance human dermal fibroblastic functions and binding strength to the deposited collagen on the titanium surface. The surface topographies of commercially pure titanium machined discs exposed to two different AH treatments were evaluated. Human dermal fibroblastic cultures grown on the discs were evaluated in terms of cellular morphology, proliferation, extracellular matrix (ECM) and proinflammatory cytokine synthesis, and physicochemical binding strength of surface-deposited collagen. An isotropically-patterned, shaggy nano-topography with a sponge-like inner network and numerous well-organized, anisotropically-patterned fine nano spikes and pores were observed on each nano-topographic surface type via scanning electron microscopy. In contrast to the typical spindle-shaped cells on the machined surfaces, the isotropically- and anisotropically-patterned nano topographic titanium surfaces had small circular/angular cells containing contractile ring-like structures and elongated, multi-shaped cells with a developed cytoskeletal network and multiple filopodia and lamellipodia, respectively. These nano-topographic surfaces enhanced dermal-related ECM synthesis at both the protein and gene levels, without proinflammatory cytokine synthesis or reduced proliferative activity. Deposited collagen fibers were included in these surfaces and sufficiently bound to the nano-topographies to resist the physical, enzymatic and chemical detachment treatments, in contrast to machined surfaces. Well-organized, isotropically-/anisotropically-patterned, nano topographic titanium surfaces with AH treatment-created nano-spikes and pores enhanced human dermal fibroblastic ECM synthesis and established sufficient mechanical integration between the surfaces and ECM to resist various detachment treatments used to experimentally mimic overloading and inflammation. PMID- 26835849 TI - Ravens attribute visual access to unseen competitors. AB - Recent studies purported to demonstrate that chimpanzees, monkeys and corvids possess a basic Theory of Mind, the ability to attribute mental states like seeing to others. However, these studies remain controversial because they share a common confound: the conspecific's line of gaze, which could serve as an associative cue. Here, we show that ravens Corvus corax take into account the visual access of others, even when they cannot see a conspecific. Specifically, we find that ravens guard their caches against discovery in response to the sounds of conspecifics when a peephole is open but not when it is closed. Our results suggest that ravens can generalize from their own perceptual experience to infer the possibility of being seen. These findings confirm and unite previous work, providing strong evidence that ravens are more than mere behaviour-readers. PMID- 26835850 TI - Work-related musculoskeletal risks associated with nurses and nursing assistants handling overweight and obese patients: A literature review. AB - BACKGROUND: Nurses and nursing assistants are susceptible to work-related musculoskeletal disorders and injuries (WMSDs) due to the increase in overweight and obese patients they are handling on a daily basis. OBJECTIVE: This study aimed to review work-related musculoskeletal hazards and risks associated with handling overweight and obese patients, and summarize the recommended interventions to mitigate musculoskeletal concerns among nurses and nursing assistants. METHODS: Approximately 350 publications were initially screened and 22 refereed articles were used to synthesize for this study on the bases of inclusion/exclusion relevance and strength of evidence on overweight or obese patient handling. RESULTS: Evidence suggested that the work-related musculoskeletal risks among nurses and nursing assistants included sprains/strains, low back pain, wrist, knee and shoulder injuries. The findings indicated that the WMSD risks increased when nurses and nursing assistants were manually moving or lifting patients, especially when the patients were overweight or obese. The recommended solutions included the lifting/transfer equipment and devices, ergonomic assessments and controls, no-lift policies, and training and education. CONCLUSION: To alleviate the risk of musculoskeletal disorders and injuries among nurses and nursing assistants handling overweight or obese patients, additional research and development into what safe patient handling interventions suit this growing population needs to be addressed. PMID- 26835851 TI - Level of agreement of occupational titles between persons with traumatic brain injury and their informants. AB - BACKGROUND: Returning to work is one of the most important goals cited by individuals with traumatic brain injury (TBI). However, they may have difficulty evoking past work history. The ability to recall work history is integral to the rehabilitation process of return to work. OBJECTIVE: The aim of this study was to determine 1) the level of agreement on the reporting of occupations and 2) if agreement is affected when specific occupational details are required in recall between adults with traumatic brain injury and their informants. METHODS: This is a retrospective cohort study of 259 individuals, with moderate to severe traumatic brain injury, and their selected informants (e.g. spouse, parent). Interviews were conducted separately for the individual and respective informant to gather information on type of occupation at time of injury and at time of interview. Reported occupations were coded using a standard classification system. Level of agreement was analyzed by interclass correlation coefficients and percent agreement, and the significance of bias was calculated. RESULTS: Participants were a mean age of 44.5 at time of study with 40% employed compared to 77% at time of injury. Agreement between participants and their informants for occupational title was high for both time periods though more so at the time of injury compared to current status. Level of agreement for specificity was moderate to high however, decreased as need for specificity of detail increased. CONCLUSION: While participant-informant responses appear to be reliable for occupational classification, when detailed information is required corroborating information is likely needed. PMID- 26835852 TI - The validity and reliability of the Interprofessional Socialization and Valuing Scale for therapy professionals. AB - BACKGROUND: Published in Work, the Interprofessional Socialization and Valuing Scale (ISVS) [1] was initially validated with 124 Canadian health profession students. The authors stated that the ISVS was useful to evaluate beliefs, behaviors, and attitudes about interprofessional practice among health profession students and professionals. OBJECTIVE: While the primary purpose of this study was to identify attitudes and behaviors in occupational, physical, and recreational therapists, and speech-language pathologists, the study also evaluated the validity and reliability of the ISVS. METHODS: The ISVS was completed by occupational, physical, and recreational therapists, and speech language pathologists in Michigan, United States of America to examine beliefs, behaviors, and attitudes towards interprofessional collaboration. Kruskal-Wallis one-way analysis of variance by ranks test was used to analyze and compare responses across disciplines. Principle component analysis identified factors from the ISVS related to attitudes and behaviors. RESULTS: While no differences were found between therapy discipline and beliefs, behaviors, and attitudes, there was a significant finding related to the validity and reliability of the ISVS for use with health professionals. CONCLUSIONS: It was found that the ISVS is valid and reliable to use with health professionals but may yield different factors than with health students. PMID- 26835853 TI - Workplace violence against nurses in three different Greek healthcare settings. AB - BACKGROUND: Healthcare workers are at high risk of facing workplace violence and nurses represent the most affected group. OBJECTIVE: This study aimed to assess workplace violence encountered by nurses working in three different healthcare settings. METHODS: This was a cross-sectional study conducted in a tertiary hospital, a non-tertiary hospital and a primary care unit. The research tool was an anonymous self-report questionnaire concerning the prevalence, characteristics, consequences, causes and preventive measures of workplace violence. The statistical analysis was performed with SPSS 17.0. RESULTS: Eighty nurses participated in the study. The majority (76%) had experienced workplace violence. Men (OR, 0.08; 95% CI, 0.01-0.56) and more experienced nurses (OR, 0.82; 95% CI, 0.70-0.97, for each additional year of working experience) were less affected in the last year. Verbal violence was the dominant type (98%). The vast majority (80%) reported a negative psychological impact, while 65% reported that they feel sometimes, rarely or never safe in their workplace. One of the main suggested causes of workplace violence was the long waiting time (99%), while the most common suggested measure of prevention was entrance control (93%). CONCLUSIONS: This study revealed a high prevalence of workplace violence against nurses working in different healthcare facilities. Country and unit-specific studies may be beneficial for implementing appropriate interventions for reducing work place violence. PMID- 26835854 TI - Pain and disability do not influence psychological and social factors at work among sick-listed patients with neck and back pain. AB - BACKGROUND: It is unknown whether living with neck and back pain, disability, and mental disorders influences the perception of psychological and social factors at work among sick-listed patients. OBJECTIVES: The primary aim of the present study was to examine the associations between pain, disability, anxiety, depression, and perceived psychological and social factors at work among sick-listed patients with neck and back pain. METHODS: We performed a cross-sectional study of 380 sick-listed patients with neck and low-back pain who were referred to spine clinics at two Norwegian university hospitals. Ordinal regression was applied, with psychological and social factors at work as the dependent variable. RESULTS: Pain was not associated with psychological and social factors at work. Disability was associated with a minor increase in the perception of demands among women, but not men. Women with high anxiety or depression scores experienced less control over work situations and less positive challenges at work. Men with high depression scores perceived low support. CONCLUSIONS: Sick-listed patients with neck and back pain who had concurrent anxiety or depression reported increased psychological and social challenges at work. To provide suitable treatment in the clinical setting, further attention should be paid to the interaction between anxiety or depression and perceived job strain. PMID- 26835847 TI - Hypertension and aging. AB - Hypertension is a highly prevalent condition with numerous health risks, and the incidence of hypertension is greatest among older adults. Traditional discussions of hypertension have largely focused on the risks for cardiovascular disease and associated events. However, there are a number of collateral effects, including risks for dementia, physical disability, and falls/fractures which are increasingly garnering attention in the hypertension literature. Several key mechanisms--including inflammation, oxidative stress, and endothelial dysfunction -are common to biologic aging and hypertension development and appear to have key mechanistic roles in the development of the cardiovascular and collateral risks of late-life hypertension. The objective of the present review is to highlight the multi-dimensional risks of hypertension among older adults and discuss potential strategies for treatment and future areas of research for improving overall care for older adults with hypertension. PMID- 26835855 TI - Group intervention: A way to improve working teams' positive psychological capital. AB - BACKGROUND: Positive psychological capital is reported to have positive effects on people's well-being and attitudes to their working lives. OBJECTIVE: The objective of this study was to investigate if it is possible to increase the level of positive psychological capital by two group intervention programs. METHODS: The research design was a controlled study with 2 * 2 experimental groups and two control groups. Two of the experimental groups received intervention I (IG I), the other two experimental groups received intervention II (IG II). Assessments were made before and after the intervention programs, with a follow-up at six months post-intervention. Instruments measuring the fundamentals of psychological capital: self-efficacy, hope, optimism, as well as health and job satisfaction were used. RESULTS: The results show that it is possible to increase the level of positive emotions, self-efficacy and job satisfaction of members of a working team by using group intervention methods. The positive changes observed at the end of the program remained six months after the intervention, with the exception of job satisfaction in IG II. It seems that the intervention had a greater influence on those persons who at the start of the study reported a low level of self-enhancement. The results were more pronounced in intervention group I where reinforcement of the resources and positive aspects of the work place environment were provided. CONCLUSIONS: A 10-week group intervention program that focused on learned optimism proved to be successful in increasing levels of self-efficacy and job satisfaction. While improvement was maintained six months post-intervention the small sample size and the attrition rate are limitations. Results are promising and further research is warranted. PMID- 26835856 TI - The effect on work ability of a tailored ergonomic learning program. AB - BACKGROUND: The physical working conditions and the musculoskeletal health of industrial workers have an effect on their work ability. OBJECTIVE: The paper evaluates the effectiveness of an ergonomic learning program focused on the development of low strain working techniques. The project is evaluated in regard to its capacity to improve and sustain the work ability of industrial workers with high physical work demands. METHOD: 249 employees at an industrial work site were followed over 21/2 years. About one third of the employees were selected into differentiated courses according to the severity of musculoskeletal disorders. The reference group consisted of the departments that did not participate. The project was evaluated by using questionnaires and interviews. RESULTS: The evaluation of the project only showed minor, non-significant increases in the work ability of the group of employees participating in the most intensive activities. Self- reported productivity increased in all departments, with the largest improvement found among the employees in the department, where everyone participated in a course (8.6% , p = 0.003). CONCLUSIONS: Work ability is composed of many different factors, physiological, physical as well as psycho social and this may explain the only limited results even of the extensive project activities in the present study. However, the evaluation indicated that job rotation in combination with more healthy work methods could sustain the work ability of employees with more severe musculoskeletal disorders. PMID- 26835857 TI - A pilot study on the operationalization of the Model of Occupational Self Efficacy: A model for the reintegration of persons with brain injuries to their worker roles. AB - BACKGROUND: Traumatic brain injury causes functional limitations that can cause people to struggle to reintegrate in the workplace despite participating in work rehabilitation programmes. OBJECTIVE: The aim of the study was to explore, and describe the experiences of individuals with Traumatic Brain Injury regarding returning to work through the use of the model of occupational self-efficacy. PARTICIPANTS: In the study 10 individuals who were diagnosed with a mild to moderate brain injury participated in the study. METHODS: The research study was positioned within the qualitative paradigm specifically utilizing case study methodology. In order to gather data from the participants, individual interviews and participant observation techniques were used. RESULTS: Two themes emerged from the findings of the study theme one reflected the barriers related to the use of the model (i.e. Theme one: Effective participation in the model is affected by financial assistance). The second theme related to the enabling factors related to the use of the model (i.e. Theme two: A sense of normality). CONCLUSION: The findings of this study indicated that the Model of Occupational Self Efficacy (MOS) is a useful model to use in retraining the work skills of individual's who sustained a traumatic brain injury. The participants in this study could maintain employment in the open labour market for a period of at least 12 months and it improved their ability to accept their brain injury as well as adapt to their worker roles. The MOS also provides a framework for facilitating community integration. PMID- 26835858 TI - The challenges that employees who abuse substances experience when returning to work after completion of employee assistance programme (EAP). AB - BACKGROUND: Employee assistance programs (EAPs) are responsible for helping employees cope with problems such as: mental distress, alcoholism and other drug dependencies, marital and financial difficulties--in short, the whole host of personal and family troubles endemic to the human condition. OBJECTIVE: The study explored the challenges that employees who abuse substances experience when returning to work after the completion of an employee assistance program. METHODS: The study used a qualitative exploratory descriptive research design. Three male participants and two key informants participated in the study. One semi structured interview was conducted with each one of the participants and one semi structured interview with the key informants. RESULTS: Four themes emerged: 1) Loss of one's worker role identity, 2) Negative influences of the community continues to effect the success of EAP, 3) EAP as a vehicle for change and, 4) Healthy occupations strengthen EAP. CONCLUSIONS: This study portrayed the following: how substance abuse effect the worker role of individuals employed in the open labor market, the challenges and facilitators experienced by employees who abuse substances when returning to their previous work roles and how occupation based interventions can be incorporated in EAP programs. Occupational therapists could use the health promotion approach, work simplification, energy conservation techniques and ergonomic analysis techniques. PMID- 26835859 TI - Preventing alcohol problems and improving drinking habits among employees: An evaluation of alcohol education. AB - BACKGROUND: In a municipality in Sweden there was a concern about the high alcohol consumption among its residents. An alcohol education program was provided to all those employed by the municipality. OBJECTIVE: To investigate whether a day-long alcohol education program provided to all employed by a Swedish municipality had an effect on alcohol consumption among employees and specifically among employees with low and higher levels of consumption respectively. METHODS: A quasi-experimental evaluation using pre-test and post test questionnaires was performed. The municipality's employees were divided in one intervention group (n: 124) and one control group (n: 139). ANOVA with repeated measures was performed on AUDIT-score and on three separate AUDIT-items: frequency of drinking, frequency of binge drinking, and typical amount consumed per drinking occasion. RESULTS: No significant effect on alcohol consumption was identified for the intervention group as a whole. Stratified analyses showed the intervention had a significant effect on reducing the frequency of binge drinking among those with the highest consumption. CONCLUSIONS: Compared to many other studies on alcohol education, some results on behaviour were found when performing stratified analyses. The employees with the highest alcohol consumption, although not labelled high consumers, reduced the frequency of binge drinking. It is difficult to speculate whether these results can be generalized to other working populations. The results have to be compared with more direct methods of reaching risk consumers, such as screening and brief interventions. Knowledge about alcohol and the associated risks of alcohol consumption might facilitate the willingness to seek help sooner. PMID- 26835860 TI - Development of a job rotation scheduling algorithm for minimizing accumulated work load per body parts. AB - BACKGROUND: For the successful implementation of job rotation, jobs should be scheduled systematically so that physical workload is evenly distributed with the use of various body parts. However, while the potential benefits are widely recognized by research and industry, there is still a need for a more effective and efficient algorithm that considers multiple work-related factors in job rotation scheduling. OBJECTIVE: This study suggests a type of job rotation algorithm that aims to minimize musculoskeletal disorders with the approach of decreasing the overall workload. METHODS: Multiple work characteristics are evaluated as inputs to the proposed algorithm. Important factors, such as physical workload on specific body parts, working height, involvement of heavy lifting, and worker characteristics such as physical disorders, are included in the algorithm. For evaluation of the overall workload in a given workplace, an objective function was defined to aggregate the scores from the individual factors. A case study, where the algorithm was applied at a workplace, is presented with an examination on its applicability and effectiveness. RESULTS: With the application of the suggested algorithm in case study, the value of the final objective function, which is the weighted sum of the workload in various body parts, decreased by 71.7% when compared to a typical sequential assignment and by 84.9% when compared to a single job assignment, which is doing one job all day. CONCLUSIONS: An algorithm was developed using the data from the ergonomic evaluation tool used in the plant and from the known factors related to workload. The algorithm was developed so that it can be efficiently applied with a small amount of required inputs, while covering a wide range of work-related factors. A case study showed that the algorithm was beneficial in determining a job rotation schedule aimed at minimizing workload across body parts. PMID- 26835861 TI - Evaluation of the match between anthropometric measures and school furniture dimensions in Chile. AB - BACKGROUND: Students are exposed to the first systematic tasks or activities that a human being carries out in his/her life while at school. In this workplace situation, school furniture is a key factor for the adoption of proper body posture. OBJECTIVE: The aim of this paper was to observe and determine the potential mismatch between school furniture dimensions and anthropometric characteristics of the students from the Valparaiso region of Chile. METHODS: The sample consisted of 3,078 volunteer participants from 18 schools (public, semi public, private). Eight anthropometric measures were gathered, together with six furniture dimensions. Mismatch analyses were carried out by using pre-defined mismatch criteria. RESULTS: Many different types of school furniture were presented at the schools. Also, a high level of mismatch was registered for seat height, desk height and seat-to-desk clearance. Finally, the analysis of all considered dimensions together showed that there was a high level of cumulative mismatch. CONCLUSIONS: It can be concluded that there were high levels of mismatch between the school furniture and student anthropometric characteristics and that this mismatch varied within the difference types of schools. This situation may have occurred because furniture acquisition was made without considering any ergonomic criteria. PMID- 26835862 TI - Long term test-retest reliability of Oswestry Disability Index in male office workers. AB - BACKGROUND: The Oswestry Disability Index (ODI) is one of the most common condition specific outcome measures used in the management of spinal disorders. But there is insufficient study on healthy populations and long term test-retest reliability. This is important because healthy populations are often used for control groups in low back pain interventions, and knowing the reliability of the controls affects the interpretation of the findings of these studies. OBJECTIVE: The purpose of this study is to determine the long term test-retest reliability of ODI in office workers. METHODS: Participants who have no chronic low back pain history were included in study. Subjects were assessed by the Turkish-ODI 2.0 (e forms) on 1st, 2nd, 4th, 8th, 15th, 30th days to determine the stability of ODI scores over time. The study began with 58 (12 female, 46 male) participants. 36 (3 female, 33 male) participated for the full 30 days. STATISTICS: Kolmogorov Smirnov and Friedman tests were used. Test-retest reliability was evaluated by using nonparametric statistics. All tests were done by using SPSS-11. RESULTS: There was no statistically significant difference among the median scores of each day. (chi= 6.482, p > 0.05). CONCLUSION: The difference between median score of the days with 1st day was neither statistically nor clinically significant. ODI has long term test re-test reliability in healthy subjects over a 1 month time interval. PMID- 26835863 TI - Maximum holding endurance time: Effects of load and load's center of gravity height. AB - BACKGROUND: Manual holding task is a potential risk to the development of musculoskeletal injuries since it is prone to induce localized muscle fatigue. Maximum holding endurance time is a significant parameter for the design of manual holding task. OBJECTIVE: This study aimed to examine the effects of load and load's COG height on maximum holding endurance time. PARTICIPANTS: Fifteen young and healthy males were recruited as participants. METHODS: A factorial design was used to examine the effects of load and load's COG height on maximum holding endurance time. Four levels of load (15% , 30% , 45% and 60% of the participant's maximum holding capacity) and two levels of load's COG height in box (0 cm and 40 cm high from the handle position) were examined. RESULTS: Maximum holding endurance time decreased with increasing load and/or increasing load's COG height. The effect of load's COG height on maximum holding endurance time decreased with increasing load. CONCLUSION: Load, load's COG height, and the interaction of load and load's COG height significantly affected maximum holding endurance time. Practitioners should realize the effects of load, load's COG height, and the interaction of load and load's COG height on maximum holding endurance time when setting the working conditions of holding tasks. PMID- 26835864 TI - Cross-cultural adaptation of the Individual Work Performance Questionnaire. AB - BACKGROUND: The Individual Work Performance Questionnaire (IWPQ), measuring task performance, contextual performance, and counterproductive work behavior, was developed in The Netherlands. OBJECTIVES: To cross-culturally adapt the IWPQ from the Dutch to the American-English language, and assess the questionnaire's internal consistency and content validity in the American-English context. METHODS: A five stage translation and adaptation process was used: forward translation, synthesis, back-translation, expert committee review, and pilot testing. During the pilot-testing, cognitive interviews with 40 American workers were performed, to examine the comprehensibility, applicability, and completeness of the American-English IWPQ. RESULTS: Questionnaire instructions were slightly modified to aid interpretation in the American-English language. Inconsistencies with verb tense were identified, and it was decided to consistently use simple past tense. The wording of five items was modified to better suit the American English language. In general, participants were positive on the comprehensibility, applicability and completeness of the questionnaire during the pilot-testing phase. Furthermore, the study showed positive results concerning the internal consistency (Cronbach's alphas for the scales between 0.79-0.89) and content validity of the American-English IWPQ. CONCLUSION: The results indicate that the cross-cultural adaptation of the American-English IWPQ was successful and that the measurement properties of the translated version are promising. PMID- 26835865 TI - Work-related stress among correctional officers: A qualitative study. AB - BACKGROUND: Correctional officers (COs) are exposed to various factors likely to jeopardize their health and safety. Even if numerous studies have been focused on work-related stress among COs, few studies have been carried out in Italy. OBJECTIVE: Indentify the work-related factors and comprehend how they negatively affect the COs' psychological health in the Italian penal system. METHODS: A qualitative approach was employed. Twenty-eight COs employed in a detention block of an Italian jail were interviewed face-to-face. For the analyses of the text, Template Analysis technique was followed. RESULTS: The analyses of the text highlighted six macro-categories and thirteen categories hierarchically linked to them: A) Intrinsic work-related factors with six categories: demanding contact with prisoners, high level of responsibility, health risks, critical events, lack of intellectual and social stimulation, and conflict value; B) Factors related to the type of contract and work organization: challenging working hours contrasted with social time, and relocation; C) Social factors: relationships with colleagues and hierarchy; D) Organizational factors: organizational injustice, E) External factors: negative social image; F) Physical environmental factors: physical structure of the prison building. CONCLUSIONS: The results indicated that COs are at high risk of stress. More specifically, the analyses highlighted that the most stressful part of the COs' job concerns their relationship with the inmates. PMID- 26835866 TI - Do gender differences matter to workplace bullying? AB - BACKGROUND: Workplace bullying has become an omnipresent problem in most organizations. Gender differences have recently received increasing attention in the workplace bullying domain. OBJECTIVE: Integrating social dominance theory with gender role theory, this study explores whether male minority and supervisor gender are related to the incidence of workplace bullying. METHODS: Data from 501 public servants employed in the tax administration institute of Taiwan was collected via a questionnaire and analyzed using hierarchical regression. RESULTS: Male minority reported more workplace bullying than did the female majority. Subordinates working with male supervisors had more exposure to bullying than those working with female supervisors. However, male supervisors did not exacerbate the relationship between male minority and workplace bullying, while females exposure to workplace bullying was attenuated when working with male supervisors. CONCLUSIONS: These findings confirm the important role of gender differences when predicting bullying at work and support the view that gender is not merely an individual antecedent of bullying, but rather acts as a social factor to influence the incidence of workplace bullying. PMID- 26835868 TI - From the Editor. PMID- 26835867 TI - Effects of sleeping position on back pain in physically active seniors: A controlled pilot study. AB - BACKGROUND: The increase in life expectancy of elderly population has aroused the interest of different knowledge areas in understanding the variables that are involved in the aging process, linking them to other concepts such as active aging, healthy aging and the bio-psycho-social changes. OBJECTIVE: This paper presents the results of the first controlled, experimental pilot study that aimed to analyze the relationship between the perception of back pain and the sleeping position adopted by physically active female seniors. METHODS: Twenty female seniors (mean age 62.70 +/- 3.827) participated in this study. The individuals were separated in 2 groups (Experimental and Control Group). For the carrying out of this study, the Visual Analogue Scale (VAS) was used to measure the intensity of back pain in the spine before and after four consecutive weeks an Intervention program. Individuals in the Experimental Group were instructed regarding the recommended way to sleep position (Intervention program) according to the pathological problems or the amount of pain reported. RESULTS: The Experimental Group (N = 10) presented significantly (p = 0.009) fewer complaints of back pain after an Intervention program in comparison to individuals who did not receive this type of information (Control Group). PMID- 26835869 TI - Vibronic Theory of Ultrafast Intersystem Crossing Dynamics in a Single Spin Crossover Molecule at Finite Temperature beyond the Born--Oppenheimer Approximation. AB - Quantum density matrix theory is carried out to study the ultrafast dynamics of the photoinduced state in a spin-crossover (SC) molecule interacting with a heat bath. The investigations are realized at finite temperature and beyond the usual Born-Oppenheimer (BO) approach. We found that the SC molecule experiences in the photoexcited state (PES) a huge internal pressure, estimated at several gigapascals, partly released in an "explosive" way within ~100 fs, causing large bond length oscillations, which dampen in the picosecond time scale because of internal conversion processes. During this regime, the BO approximation is not valid. Depending on the tunneling strength, the ultrafast relaxation may proceed through the thermodynamic metastable high-spin state or prevent it. Interestingly, we demonstrate that final relaxation toward the low-spin state always follows a local equilibrium pathway, where the BO approach is valid. Our formulation reconciles the nonequilibrium and the equilibrium properties of this fascinating phenomenon and opens the way to quantum studies on cluster molecules. PMID- 26835870 TI - Effects of different weight loss intervention programmes in health clubs - an observational multicenter study. AB - This study aimed at comparing the effectiveness of three lifestyle intervention programmes in health clubs "exercise only" (E), "exercise plus nutritional counselling" (E + NC), and "exercise plus weight loss program" (E + WLP) on weight loss under real-life conditions. An observational multicenter study including 788 overweight/obese new customers of 95 health clubs in Germany was performed. Participants chose E (n = 512, 38 +/- 14 year, BMI 30.4 +/- 4.7 kg/m(2)), E + NC (n = 179, 42 +/- 14 year, BMI 31.7 +/- 4.5 kg/m(2)), or E + WLP (n = 97, 40 +/- 11 year, BMI 31.6 +/- 5.1 kg/m(2)). Anthropometric data, energy expenditure, and energy intake were assessed at baseline and after 3 months. All groups significantly reduced body weight (E: -1.5 +/- 2.9 kg, E + NC: -3.4 +/- 3.6 kg, E + WLP: -5.5 +/- 4.3 kg, p < .001 within and between groups) and body fat (E: -1.2 +/- 2.4%, E + NC: -2.0 +/- 2.4%, E + WLP: -3.1 +/- 2.5%, p < .001 within and between groups). However, only E + WLP achieved a clinically significant weight loss of -5.9 +/- 3.9%. Exercise energy expenditure increased and energy intake decreased significantly in all groups (p < .001), but to different extents. This investigation suggests that under field conditions exercise plus dietary interventions are more effective for weight loss than exercise alone. The benefits of E + WLP emphasize that interventions even performed by health clubs may elicit clinically relevant weight loss in overweight and obese new customers and can therefore be recommended. PMID- 26835871 TI - Astigmatic Peripheral Defocus with Different Contact Lenses: Review and Meta Analysis. AB - PURPOSE: To review the level of relative peripheral defocus measured with different devices with potential use for myopia retention. To present comparative data of the change in astigmatic peripheral refraction with different contact lenses evaluated in different studies conducted in the same laboratory following the same methodology in myopic human eyes Methods: A joint analysis of work, carried out at the same laboratory (CEORLab) in 137 myopic subjects with different types of contact lenses (CL), was performed to obtain the tangential (FT = M - J0), sagittal (FS = M + J0), and mean (M) power refractive errors (M and J0 are the refraction vector components). Orthokeratology, standard aspheric rigid gas-permeable (RGP), experimental RGP, experimental soft CL, and different multifocal soft CL were used to induce peripheral myopic defocus (236 peripheral refraction measures). RESULTS: Compared with values obtained in naked eye condition (baseline), only three of the eight approaches tested show statistically significant peripheral myopic defocus induction (p < 0.001) in both temporal and nasal retina (orthokeratology, experimental RGP, and Proclear multifocal CL with Add: +3.00 D). Standard aspheric RGP also produced a significant increase in myopic defocus for the FT, of about -2.00 D. The experimental soft CL, designed to mimic the peripheral performance of the experimental RGP, induced a similar effect to the standard aspheric soft CL. CONCLUSION: Orthokeratology, multifocal soft CL, and custom-designed RGP CL were able to generate a significant relative peripheral myopia in myopic eyes. Conversely, standard and experimental soft CL were not able to induce significant peripheral myopic and astigmatic defocus values. PMID- 26835872 TI - Genotyping and strain distribution of Mycobacterium avium subspecies hominissuis isolated from humans and pigs in Belgium, 2011-2013. AB - Mycobacterium avium represents a health concern for both humans and pigs. The characterisation of its subspecies is an important step improving the understanding of the epidemiology and the control of this pathogen. Ninety-two human M. avium strains were selected for a retrospective study. Subspecies determination by rpoB sequencing and IS1245/IS901 analysis showed that 98.9% of Belgian human M. avium strains belong to the subspecies hominissuis (MAH). Some of these MAH strains present particular IS1245/IS901 profiles (absence of IS1245 and false IS901 detection provoked by the presence of ISMav6). In addition, 54 MAH strains isolated from submandibular lymph nodes of Belgian pigs with lymphadenitis were included in this study. Genotyping of human and porcine isolates was performed using multispacer sequence typing (MST). In total, 49 different MST types were identified among pig (n = 11) and human (n = 43) MA isolates, with only five shared by both hosts. Among these MST types, 34 were newly identified. Our findings demonstrate the extensive genetic diversity among MAH isolates. Some genotypes were more prevalent in human or pigs but no correlation was observed between MST type and place of residence or the farm of origin for human and porcine isolates respectively, suggesting an environmental source of infection. PMID- 26835873 TI - Iterative design of emetine-based prodrug targeting fibroblast activation protein (FAP) and dipeptidyl peptidase IV DPPIV using a tandem enzymatic activation strategy. AB - BACKGROUND: There is an urgent need to develop new agents for treating metastatic prostate cancer to overcome multiple drug resistance to the current standard targeted cancer therapy. Emetine is a highly cytotoxic natural product protein synthesis inhibitor, which is toxic to all cell types. Its cytotoxicity can be blocked by derivatizing its N-2' position. Thus emetine can be selectively delivered to cancer cells in the region of metastatic cancer as a prodrug that will be activated by an enzyme selectively overexpressed within the metastatic tumor microenvironment. In this work, we convert emetine to a prodrug activatable by the fibroblast activation protein (FAP), a serine protease overexpressed by the carcinoma associated fibroblasts. METHOD: By using an iterative structure activity relationship strategy, several peptidyl emetine prodrug analogs (1-11) were synthesized by chemical derivatization of emetine at its N-2' position and tested for in-vitro activation by FAP. The lead prodrug 11 is made up of a DPPIV activatable prodrug precursor 10 (Ala-Pro-PABC-Emetine) coupled to FAP substrate (Ala-Ser-Gly-Pro-Ala-Gly-Pro). Activation assays of the prodrugs were performed in purified FAP, DPPIV, FBS, and human serum and were analyzed by LCMS. In vitro cytotoxicity assays of these prodrugs are carried out in prostate (LNCaP, PC3) and breast (MCF7 and MDA-MB-231) cancer cell lines. The prodrugs are also tested in normal immortalized human prostatic epithelial cell line (PrEC). RESULTS: The lead FAP activated emetine prodrug 11 is activated to emetine in tandem by FAP and DPPIV in about 70% conversion within 24 hr. In prostate and breast cancer cell lines treated with prodrug 11, it is found to be equipotent with emetine in the presence of FAP and DPPIV. However, in the PrEC cell line grown in serum free media, prodrug 11 is more than 200-fold less cytotoxic than emetine in the absence of FAP and DPPIV. CONCLUSION: This FAP activated prodrug of cytotoxic agent emetine further shows the crucial role of the N-2' position of emetine in controlling its cytotoxicity. Significantly reduced toxicity observed in the PrEC cell line in the absence of FAP and DPPIV shows that prodrug 11 could be systemically delivered to regions of metastatic prostate cancer or other solid tumor for activation by cancer selective enzymes within the cancer microenvironment, such as FAP that is overexpressed by the carcinoma-associated fibroblasts. The two-step tandem enzymatic activation of prodrug 11 by FAP and DPPIV is a strategy for overcoming steric hindrance. PMID- 26835875 TI - On the Challenge of Maladaptive and Impulsive Aggression in the Clinical Treatment Setting. PMID- 26835874 TI - Trigonella foenum-graecum Seed Extract, 4-Hydroxyisoleucine, and Metformin Stimulate Proximal Insulin Signaling and Increase Expression of Glycogenic Enzymes and GLUT2 in HepG2 Cells. AB - BACKGROUND: Fenugreek (Trigonella foenum-graecum) is globally recognized for its medicinal properties and hypoglycemic effects. The seed extract as well as its active compound, 4-hydroxyisoleucine (4-OH-Ile), have been shown to reduce hyperglycemic insulin resistance. The mechanism by which this occurs has not been investigated in human liver cells (HepG2) in comparison to the antihyperglycemic drug, metformin. METHODS: We investigated the effects of an aqueous fenugreek seed extract (FSE), 4-OH-Ile, and metformin in HepG2 cells relative to insulin as a positive control. Cells were treated with FSE and 4-OH-Ile at 100 ng/mL under normoglycemic (5 mM glucose) and hyperglycemic (30 mM glucose) conditions for 72 hr. Tyrosine phosphorylation of insulin receptor-beta (IR-beta), protein kinase B (Akt), glycogen synthase kinase-3alpha/beta (GSK-3alpha/beta), and glucose transporter 2 (GLUT2) was determined by western blotting. Gene expression of sterol regulatory element-binding protein 1c (SREBP1c), GLUT2, glycogen synthase (GS), and glucokinase (GK) was evaluated by quantitative polymerase chain reaction, and supernatant glucose levels were measured using the Piccolo biochemistry analyzer. RESULTS: Under normo- and hyperglycemic conditions, FSE, 4 OH-Ile, insulin (100 ng/mL), and metformin (2 mM) caused a significant increase in phosphorylation of IR-beta, Akt, GSK-3alpha/beta, and GLUT2. Glucose uptake, however, was most significantly increased in FSE-treated cells during both conditions. FSE induced the most significant changes in downstream insulin signaling, GS, GK, SREBP1c, and GLUT2 expression compared to 4-OH-Ile, metformin, and insulin. In addition, FSE significantly increased glucose uptake. CONCLUSIONS: Collectively, these findings provide a mechanism by which FSE exerts antihyperglycemic effects similar to metformin and insulin that occurs via enhanced insulin signaling, gene expression, and increasing glucose uptake. PMID- 26835877 TI - Human epidermal growth factor receptor 3 in head and neck squamous cell carcinomas. AB - Human epidermal growth factor receptor 3 (HER3) is a member of the human epidermal growth factor receptor (HER) family. The main characteristic of HER3 is that it does not possess tyrosine kinase activity, unlike other HERs. The role of HER3 in tumorigenesis has now been recognized, particularly in head and neck squamous cell carcinomas (HNSCCs). Despite conflicting studies, HER3 was found to be overexpressed in HNSCC samples, and correlates with disease progression and poor survival, especially when it is coexpressed with other HERs. HER3 is a significant factor in HNSCC treatment resistance. Indeed, HER3 is a major mechanism described for cetuximab resistance because of modification of epidermal growth factor receptor (EGFR) internalization and by phosphotidylinositol-3 kinase (PI3K)/AKT signaling pathway activation. HER3 also affects resistance to tyrosine kinase inhibitors (TKIs) and thereby promotes treatment escape and radiotherapy resistance by activation of the survival signaling pathway. To counteract this, pharmacologic inhibitors of HER3 are currently in development and could significantly improve HNSCC treatment. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2412-E2418, 2016. PMID- 26835876 TI - A phase 3b study of sofosbuvir plus ribavirin in Taiwanese patients with chronic genotype 2 hepatitis C virus infection. AB - BACKGROUND & AIMS: In Taiwan, patients with chronic hepatitis C virus (HCV) infection are currently treated with pegylated interferon-alpha plus ribavirin, but interferon-based regimens can be poorly tolerated, especially by those with advanced liver disease and the elderly. Sofosbuvir, an oral nucleotide analogue inhibitor of HCV NS5B polymerase, is approved in Europe, the USA and Japan for treating chronic HCV infection. This phase 3b study examined the efficacy and safety of sofosbuvir plus ribavirin in Taiwanese patients with chronic genotype 2 HCV infection +/- compensated cirrhosis. METHODS: In this multicentre, open label, phase 3b (NCT02021643) study, 87 patients (n = 43, treatment-naive; n = 44, treatment-experienced) received 12 weeks of treatment with sofosbuvir plus weight-based ribavirin. The primary efficacy endpoint was the proportion of patients with sustained virological response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were also collected. RESULTS: All 87 patients (100%; 95% confidence interval, 92-100%) achieved SVR12, including the 13 patients with compensated cirrhosis. The most common treatment emergent adverse events (AEs) were insomnia (16%, 14/87) and upper respiratory tract infection (16%, 14/87). No grade 3 or grade 4 AE was reported. There was one serious AE (biliary colic), which was deemed unrelated to study treatment. Laboratory abnormalities other than ribavirin-related reductions in haemoglobin were uncommon. CONCLUSIONS: The results from this phase 3b study demonstrate that 12 weeks of treatment with the interferon-free regimen sofosbuvir plus ribavirin is effective and well tolerated in both treatment-naive and treatment-experienced Taiwanese patients with chronic genotype 2 HCV infection. PMID- 26835878 TI - An Intrinsically Disordered Peptide Facilitates Non-Endosomal Cell Entry. AB - Many cell-penetrating peptides (CPPs) fold at cell surfaces, adopting alpha- or beta-structure that enable their intracellular transport. However, the same structural folds that facilitate cellular entry can also elicit potent membrane lytic activity, limiting their use in delivery applications. Further, a distinct CPP can enter cells through many mechanisms, often leading to endosomal entrapment. Herein, we describe an intrinsically disordered peptide (CLIP6) that exclusively employs non-endosomal mechanisms to cross cellular membranes, while being remarkably biocompatible and serum-stable. We show that a single anionic glutamate residue is responsible for maintaining the disordered bioactive state of the peptide, defines its mechanism of cellular entry, and is central to its biocompatibility. CLIP6 can deliver membrane-impermeable cargo directly to the cytoplasm of cells, suggesting its broad utility for delivery of drug candidates limited by poor cell permeability and endosomal degradation. PMID- 26835879 TI - Exciton-Plasmon Coupling and Electromagnetically Induced Transparency in Monolayer Semiconductors Hybridized with Ag Nanoparticles. AB - Exciton-plasmon coupling in hybrids of a monolayer transition metal dichalcogenide and Ag nanoparticles is investigated in the weak and strong coupling regimes. In the weak coupling regime, both absorption enhancement and the Purcell effect collectively modify the photoluminescence properties of the semiconductor. In the strong coupling regime, electromagnetically induced transparency dips are displayed, evidencing coherent energy exchange between excitons and plasmons. PMID- 26835880 TI - Metal-free Nanoporous Carbon as a Catalyst for Electrochemical Reduction of CO2 to CO and CH4. AB - S-doped and dual S,N-doped polymer-derived carbons were studied as electrocatalysts for the reduction of CO2. Higher Faradaic efficiencies for conversion to CO and CH4 were obtained for S,N-doped carbon than its S-doped counterpart. The former showed a maximum Faradaic efficiency of 11.3% for CO and 0.18% for CH4 formation. The S,N-nanoporous carbon was better at decreasing the overpotential of the reduction process. The pyridinic nitrogen groups were found to be actively participating in binding CO2. The quaternary nitrogen and thiophenic groups were also involved in the reduction process. It is proposed that the positively charged sites on the carbon atoms, adjacent to pyridinic nitrogen, stabilize the CO2(.-) and COOH* intermediates, promoting the formation of CO. The surface basicity of the catalysts improved the CO2 reduction selectivity when competing with H2 evolution. N2 adsorption measurements suggested that ultra-micropores enhance the reduction of CO2 to CH4. PMID- 26835881 TI - Phage display selection of tight specific binding variants from a hyperthermostable Sso7d scaffold protein library. AB - Antibodies, the quintessential biological recognition molecules, are not ideal for many applications because of their large size, complex modifications, and thermal and chemical instability. Identifying alternative scaffolds that may be evolved into tight, specific binding molecules with improved physical properties is of increasing interest, particularly for biomedical applications in resource limited environments. Hyperthermophilic organisms, such as Sulfolobus solfataricus, are an attractive source of highly stable proteins that may serve as starting points for alternative molecular recognition scaffolds. We describe the first application of phage display to identify binding proteins based on the S. solfataricus protein Sso7d scaffold. Sso7d is a small cysteine-free DNA binding protein (approximately 7 kDa, 63 amino acids), with a melting temperature of nearly 100 degrees C. Tight-binding Sso7d variants were selected for a diverse set of protein targets from a 10(10) member library, demonstrating the versatility of the scaffold. These Sso7d variants are able to discriminate among closely related human, bovine and rabbit serum albumins. Equilibrium dissociation constants in the nanomolar to low micromolar range were measured via competitive ELISA. Importantly, the Sso7d variants continue to bind their targets in the absence of the phage context. Furthermore, phage-displayed Sso7d variants retain their binding affinity after exposure to temperatures up to 70 degrees C. Taken together, our results suggest that the Sso7d scaffold will be a complementary addition to the range of non-antibody scaffold proteins that may be utilized in phage display. Variants of hyperthermostable binding proteins have potential applications in diagnostics and therapeutics for environments with extreme conditions of storage and deployment. PMID- 26835882 TI - Diversity and variation in antimicrobial susceptibility patterns over time in Mycoplasma agalactiae isolates collected from sheep and goats in France. AB - AIMS: Mycoplasma agalactiae is responsible for Contagious Agalactia, a severe syndrome affecting small ruminants worldwide and resulting in significant economic losses in countries with an important dairy industry. The aim of this study was to examine the antimicrobial susceptibility patterns of M. agalactiae isolates in France, their evolution over the last 25 years and their relationships with the genetic diversity of isolates and their origin (geographical and animal host). METHODS AND RESULTS: Susceptibility patterns were determined by measuring minimal inhibitory concentrations (MICs) of several antimicrobials used against mycoplasmas. Caprine M. agalactiae strains showed increased MICs over time for most of the antimicrobials tested, except fluoroquinolones. This susceptibility loss was homogeneous despite the considerable genetic and geographical heterogeneity of the isolates. In contrast, all the ovine isolates originating from a single clone and the same region showed increased MICs only to some macrolides. CONCLUSIONS: MICs have evolved differently depending on the origin of the isolates but the overall loss in susceptibility has remained far more moderate than that of Mycoplasma bovis, a cattle pathogen closely related to M. agalactiae. SIGNIFICANCE AND IMPACT OF THE STUDY: Several hypotheses are proposed to explain the differences in susceptibility patterns, such as local, specific, nonmycoplasma-targeting antibiotic treatments and the genetic background of isolates in connection with their animal host. PMID- 26835883 TI - Emerging roles for collagen XV and XVIII in cancer progression. PMID- 26835885 TI - SNPs in transporter and metabolizing genes as predictive markers for oxaliplatin treatment in colorectal cancer patients. AB - Oxaliplatin is frequently used as part of a chemotherapeutic regimen with 5 fluorouracil in the treatment of colorectal cancer (CRC). The cellular availability of oxaliplatin is dependent on metabolic and transporter enzymes. Variants in genes encoding these enzymes may cause variation in response to oxaliplatin and could be potential predictive markers. Therefore, we used a two step procedure to comprehensively investigate 1,444 single nucleotide polymorphisms (SNPs) from these pathways for their potential as predictive markers for oxaliplatin treatment, using 623 stage II-IV CRC patients (of whom 201 patients received oxaliplatin) from a German prospective patient cohort treated with adjuvant or palliative chemotherapy. First, all genes were screened using the global test that evaluated SNP*oxaliplatin interaction terms per gene. Second, one model was created by backward elimination on all SNP*oxaliplatin interactions of the selected genes. The statistical procedure was evaluated using bootstrap analyses. Nine genes differentially associated with overall survival according to oxaliplatin treatment (unadjusted p values < 0.05) were selected. Model selection resulted in the inclusion of 14 SNPs from eight genes (six transporter genes, ABCA9, ABCB11, ABCC10, ATP1A1, ATP1B2, ATP8B3, and two metabolism genes GSTM5, GRHPR), which significantly improved model fit. Using bootstrap analysis we show an improvement of the prediction error of 3.7% in patients treated with oxaliplatin. Several variants in genes involved in metabolism and transport could thus be potential predictive markers for oxaliplatin treatment in CRC patients. If confirmed, inclusion of these variants in a predictive test could identify patients who are more likely to benefit from treatment with oxaliplatin. PMID- 26835886 TI - The role of filaggrin mutations during pregnancy and postpartum: atopic dermatitis and genital skin diseases. AB - Mutations in the epidermal filaggrin gene (FLG) are associated with skin barrier dysfunction (dry skin, less acidic skin, and fissured skin), and atopic dermatitis (AD) with a severe and persistent course. Because pregnancy and delivery further impairs normal skin barrier functions (immune suppression, mechanical stress), we studied the possible role of FLG mutations on the risk of AD flares, genital infections, and postpartum problems related to perineal trauma. FLG-genotyping was performed in a population-based sample of 1837 women interviewed in the 12th and 30th weeks of pregnancy and 6 months postpartum as part of the Danish National Birth Cohort study 1996-2002. We found that FLG mutations also influence pregnancy-related skin disease; thus, women with FLG mutations had an increased risk of AD flares during pregnancy (OR 10.5, 95% CI 3.6-30.5) and of enduring postpartum physical problems linked to perineal trauma during delivery (OR 11.1, 95% CI 1.1-107.7). PMID- 26835887 TI - Differences in Risk Factors for Anemia Between Adolescent and Adult Women. AB - BACKGROUND: Iron deficiency anemia (IDA) affects 2%-5% of reproductive-age women. Screening is based on risk factors, such as a low-iron diet and menstruation. However, published IDA risk factors fail to consider age-related risks specific to adolescent women, potentially limiting identification of high-risk adolescents for objective testing. The goal of the study was to examine IDA risk factors in a nationally representative sample of younger (12-21 years) and older (22-49 years) reproductive-age women. MATERIALS AND METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. IDA was defined using hemoglobin, ferritin, soluble transferrin receptor, standard NHANES laboratory measures. Sex-, age-, and race-specific hemoglobin values defined anemia. Iron deficiency was calculated using ferritin and soluble transferrin receptor in the body iron formula. Logistic regression assessed the association of potential risk factors (race, body mass index, poverty, iron intake, tobacco/nicotine exposure, physical activity, menses, and contraceptive use) with IDA in younger and older women. RESULTS: The prevalence of IDA was 2.4% and 5.5% among younger and older women, respectively. Among younger women, contraceptive use was marginally protective from IDA (risk ratio 0.50, 95% confidence interval [CI] 0.25-1.00). Among older women, significant variables included Black race (risk ratio 2.31, 95% CI 1.33-4.02) and increased years menstruating (>=25 years vs. <25 years; risk ratio 1.93, 95% CI 0.99-3.76). CONCLUSIONS: Risk factors for IDA among older reproductive-age women do not apply to adolescent women. To better inform the timing and frequency of screening recommendations, further research must identify adolescent-specific IDA risk factors. PMID- 26835888 TI - Insight into octoploid strawberry (Fragaria) subgenome composition revealed by GISH analysis of pentaploid hybrids. AB - As the product of interspecific hybridization between its two ancestral octoploid (2n = 8x = 56) species (Fragaria chiloensis and F. virginiana), the cultivated strawberry (F. *ananassa) is among the most genomically complex of crop plants, harboring subgenomic components derived from as many as four different diploid ancestors. To physically visualize the octoploids' subgenome composition(s), we launched molecular cytogenetic studies using genomic in situ hybridization (GISH), comparative GISH (cGISH), and rDNA-FISH techniques. First, GISH resolution in Fragaria was tested by using diploid and triploid hybrids with predetermined genome compositions. Then, observation of an octoploid genome was implemented by hybridizing chromosomes of pentaploid (2n = 5x = 35) hybrids from F. vesca * F. virginiana with genomic DNA probes derived from diploids (2n = 2x = 14) F. vesca and F. iinumae, which have been proposed by phylogenetic studies to be closely related to the octoploids yet highly divergent from each other. GISH and cGISH results indicated that octoploid-derived gametes (n = 4x = 28) carried seven chromosomes with hybridization affinities to F. vesca, while the remaining 21 chromosomes displayed varying affinities to F. iinumae, indicating differing degrees of subgenomic contribution to the octoploids by these two putatively ancestral diploids. Combined rDNA-FISH revealed severe 25S rDNA loss in both the F. vesca- and F. iinumae-like chromosome groups, while only the prior group retained its 5S loci. PMID- 26835889 TI - Meta-analysis of the efficacy and safety of prazosin versus placebo for the treatment of nightmares and sleep disturbances in adults with posttraumatic stress disorder. AB - Although sleep disturbances occur commonly in patients with posttraumatic stress disorder (PTSD) and are associated with adverse outcomes and increased suicidality, they are often inadequately addressed by antidepressant medications. OBJECTIVE: This review aims to assess whether prazosin reduces nightmares, sleep disturbances, and illness severity in adults with PTSD. METHOD: Electronic databases (PubMed, PsycINFO) were searched in September 2014 for randomized controlled trials in adults. Search terms included posttraumatic stress disorder, prazosin, nightmares, and sleep disturbance. Included studies used prazosin and provided objective outcome data related to nightmares and/or sleep quality. RESULTS: Six studies (191 participants) met the criteria for inclusion. Prazosin was more effective than placebo in improving nightmares (standardized mean difference [SMD] = 1.022, 95% confidence interval [CI] [0.41, 1.62], p = .001), sleep quality (SMD = 0.93, 95% CI [-0.02, 1.88], p = .054; and SMD = 1.14, 95% CI [0.24, 2.03], p = .01), and illness severity (SMD = 1.20, 95% CI [0.79, 1.61], p = .001, with no significant effect on systolic (SMD = -0.01, 95% CI [-0.40, 0.37], p = .94) or diastolic (SMD = 0.30, 95% CI [-0.09, 0.68], p = .154) blood pressure. CONCLUSION: PTSD-related nightmares, sleep disturbances, and overall illness severity showed a significant response to treatment with prazosin. With careful dose titration, prazosin was well tolerated and had no significant sustained effect on blood pressure. PMID- 26835892 TI - Pulmonary and Critical Care Medicine Program Directors' Attitudes toward Training in Medical Education. A Nationwide Survey Study. AB - RATIONALE: Many pulmonary and critical care medicine (PCCM) fellows are interested in improving their teaching skills as well as learning about careers as clinician educators. Educational opportunities in PCCM fellowship programs designed to address these interests have not been well characterized in U.S. training programs. OBJECTIVES: We aimed to characterize educational content and structure for training fellows to teach in PCCM fellowship programs. We evaluated three major domains: (1) existing educational opportunities, (2) PCCM program directors' attitudes toward the importance of teaching fellows how to teach, and (3) potential components of an optimal teaching skills curriculum for PCCM fellows. METHODS: We surveyed program and associate program directors who were members of the Association of Pulmonary and Critical Care Medicine Program Directors in 2014. Survey domains included existing teaching skills content and structure, presence of a formal medical education curriculum or clinician educator track, perceived barriers to teaching fellows teaching skills, and open ended qualitative inquiries about the ideal curricula. Data were analyzed both quantitatively and qualitatively. MEASUREMENTS AND MAIN RESULTS: Of 158 invited Association of Pulmonary and Critical Care Medicine Program Directors members, 85 program directors and associate directors responded (53.8% response rate). Annual curricular time dedicated to teaching skills varied widely (median, 3 h; mean, 5.4 h; interquartile range, 2.0-6.3 h), with 17 respondents (20%) allotting no time to teaching fellows to teach and 14 respondents (17%) dedicating more than 10 hours. Survey participants stated that the optimal duration for training fellows in teaching skills was significantly less than what they reported was actually occurring (median optimal duration, 1.5 h/yr; mean, 2.1 h/yr; interquartile range, 1.5-3.5 h/yr; P < 0.001). Only 28 (33.7%) had a formal curriculum for teaching medical education skills. Qualitative analyses identified several barriers to implementing formal teaching skills curricula, including "time," "financial resources," "competing priorities," and "lack of expert faculty." CONCLUSIONS: While prior work has demonstrated that fellows are interested in obtaining medical education skills, PCCM program directors and associate directors noted significant challenges to implementing formal educational opportunities to teach fellows these skills. Effective strategies are needed to design, implement, sustain, and assess teaching skills curricula for PCCM fellowships. PMID- 26835884 TI - Rapid brain MRI acquisition techniques at ultra-high fields. AB - Ultra-high-field MRI provides large increases in signal-to-noise ratio (SNR) as well as enhancement of several contrast mechanisms in both structural and functional imaging. Combined, these gains result in a substantial boost in contrast-to-noise ratio that can be exploited for higher-spatial-resolution imaging to extract finer-scale information about the brain. With increased spatial resolution, however, there is a concurrent increased image-encoding burden that can cause unacceptably long scan times for structural imaging and slow temporal sampling of the hemodynamic response in functional MRI - particularly when whole-brain imaging is desired. To address this issue, new directions of imaging technology development - such as the move from conventional 2D slice-by-slice imaging to more efficient simultaneous multislice (SMS) or multiband imaging (which can be viewed as "pseudo-3D" encoding) as well as full 3D imaging - have provided dramatic improvements in acquisition speed. Such imaging paradigms provide higher SNR efficiency as well as improved encoding efficiency. Moreover, SMS and 3D imaging can make better use of coil sensitivity information in multichannel receiver arrays used for parallel imaging acquisitions through controlled aliasing in multiple spatial directions. This has enabled unprecedented acceleration factors of an order of magnitude or higher in these imaging acquisition schemes, with low image artifact levels and high SNR. Here we review the latest developments of SMS and 3D imaging methods and related technologies at ultra-high field for rapid high-resolution functional and structural imaging of the brain. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26835891 TI - Intra-Wound Antibiotics and Infection in Spine Fusion Surgery: A Report from Washington State's SCOAP-CERTAIN Collaborative. AB - BACKGROUND: Surgical site infection (SSI) after spine surgery is classified as a "never event" by the Centers for Medicare and Medicaid. Intra-wound antibiotics (IWA) have been proposed to reduce the incidence of SSI, but robust evidence to support its use is lacking. METHODS: Prospective cohort undergoing spine fusion at 20 Washington State hospitals (July 2011 to March 2014) participating in the Spine Surgical Care and Outcomes Assessment Program (Spine SCOAP) linked to a discharge tracking system. Patient, hospital, and operative factors associated with SSI and IWA use during index hospitalizations through 600 days were analyzed using a random effects logistic model (index), and a time-to-event analysis (follow-up) using Cox proportional hazards. RESULTS: A total of 9,823 patients underwent cervical (47%) or lumbar (53%) procedures (mean age, 58; 54% female) with an SSI rate of 1.1% during index hospitalization. Those with SSI were older, more often had diabetes mellitus, and more frequently underwent lumbar (versus cervical) fusion compared with those without SSI (all p < 0.01). Unadjusted rates of SSI during index hospitalization were lower in patients who received IWA (0.8% versus 1.5%). After adjustment for patient, hospital, and operative factors, no benefit was observed in those receiving IWA (odds ratio [OR] 0.65, 95% confidence interval [CI]: 0.42-1.03). At 12 mo, unadjusted rates of SSI were 2.4% and 3.0% for those who did and did not receive antibiotics; after adjustment there was no significant difference (hazard ratio [HR] 0.94, 95% CI: 0.62-1.42). CONCLUSIONS: Whereas unadjusted analyses indicate a nearly 50% reduction in index SSI using IWA, we did not observe a statistically significant difference after adjustment. Despite its size, this study is underpowered to detect small but potentially relevant improvements in rates of SSI. It remains to be determined if IWA should be promoted as a quality improvement intervention. Concerns related to bias in the use of IWA suggest the benefit of a randomized trial. PMID- 26835890 TI - Current and future effects of varicella and herpes zoster vaccination in Germany Insights from a mathematical model in a country with universal varicella vaccination. AB - Varicella zoster virus (VZV) is primarily known for causing varicella in childhood, but can reactivate again as herpes zoster (HZ) after a period of latency, mainly in persons older than 50 years. Universal varicella vaccination was introduced in Germany in 2004, while HZ vaccination has not been recommended yet. We aimed to quantify the potential long-term effects of universal childhood varicella vaccination and HZ vaccination of the elderly on varicella and HZ incidence in Germany over a time horizon of 100 years, using a transmission model calibrated to pre-vaccination data and validated against early post-vaccination data. Using current vaccination coverage rates of 87% (64%) with one (two) varicella vaccine dose(s), the model predicts a decrease in varicella cases by 89% for the year 2015. In the long run, the incidence reduction will stabilize at about 70%. Under the assumption of the boosting hypothesis of improved HZ protection caused by exposure to VZV, the model predicts a temporary increase in HZ incidence of up to 20% for around 50 years. HZ vaccination of the elderly with an assumed coverage of 20% has only limited effects in counteracting this temporary increase in HZ incidence. However, HZ incidence is shown to decrease in the long-term by 58% as vaccinated individuals get older and finally reach age classes with originally high HZ incidence. Despite substantial uncertainties around several key variables, the model's results provide valuable insights that support decision-making regarding national VZV vaccination strategies. PMID- 26835893 TI - A label-free electrochemical sensor for detection of mercury(II) ions based on the direct growth of guanine nanowire. AB - A simple, sensitive and label-free electrochemical sensor is developed for detection of Hg(2+) based on the strong and stable T-Hg(2+)-T mismatches. In the presence of Mg(2+), the parallel G-quadruplex structures could be specifically recognized and precipitated in parallel conformation. Therefore, the guanine nanowire was generated on the electrode surface, triggering the electrochemical H2O2-mediated oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). In this research, a new method of signal amplification for the quantitative detection of Hg(2+) was described based on the direct growth of guanine nanowire via guanine nanowire. Under optimum conditions, Hg(2+) was detected in the range of 100 pM 100 nM, and the detection limit is 33 pM. Compared to the traditional single G quadruplex label unit, this electrochemical sensor showed high sensitivity and selectivity for detecting Hg(2+). PMID- 26835894 TI - The influence of salinity on the toxicity of selected sulfonamides and trimethoprim towards the green algae Chlorella vulgaris. AB - This paper presents the investigation of the influence of salinity variations on the toxicity of sulfapyridine, sulfamethoxazole, sulfadimethoxine and trimethoprim towards the green algae Chlorella vulgaris after exposure times of 48 and 72 h. In freshwater the EC50 values ranged from 0.98 to 123.22 mg L(-1) depending on the compound. The obtained results revealed that sulfamethoxazole and sulfapyridine were the most toxic, while trimethoprim was the least toxic pharmaceutical to the selected organism. Deviations between the nominal and real test concentrations were determined via instrumental analysis to support the interpretation of ecotoxicological data. The toxicity effects were also tested in saline water (3, 6 and 9 PSU). The tendency that the toxicity of selected pharmaceuticals decreases with increasing salinity was observed. Higher salinity implies an elevated concentration of inorganic monovalent cations that are capable of binding with countercharges available on algal surfaces (hydroxyl functional groups). Hence it can reduce the permeability of pharmaceuticals through the algal cell walls, which could be the probable reason for the observed effect. Moreover, for the classification of the mode of toxic action, the toxic ratio concept was applied, which indicated that the effects of the investigated drugs towards algae are caused by the specific mode of toxic action. PMID- 26835895 TI - Effects of inorganic anions on carbon isotope fractionation during Fenton-like degradation of trichloroethene. AB - Understanding the magnitude and variability in isotope fractionation with respect to specific processes is crucial to the application of stable isotopic analysis as a tool to infer and quantify transformation processes. The variability of carbon isotope fractionation during Fenton-like degradation of trichloroethene (TCE) in the presence of different inorganic ions (nitrate, sulfate, and chloride), was investigated to evaluate the potential effects of inorganic anions on carbon isotope enrichment factor (epsilon value). A comparison of epsilon values obtained in deionized water, nitrate solution, and sulfate solution demonstrated that the epsilon values were identical and not affected by the presence of nitrate and sulfate. In the presence of chloride, however, the epsilon values (ranging from -6.3+/-0.8 to 10+/-1.30/00) were variable and depended on the chloride concentration, indicating that chloride could significantly affect carbon isotope fractionation during Fenton-like degradation of TCE. Thus, caution should be exercised in selecting appropriate epsilon values for the field application of stable isotope analysis, as various chloride concentrations may be present due to naturally present or introduced with pH adjustment and iron salts during Fenton-like remediation. Furthermore, the effects of chloride on carbon isotope fractionation may be able to provide new insights about reaction mechanisms of Fenton-like processes. PMID- 26835896 TI - Rapid dehalogenation of pesticides and organics at the interface of reduced graphene oxide-silver nanocomposite. AB - This paper reports dehalogenation of various organohalides, especially aliphatic halocarbons and pesticides at reduced graphene oxide-silver nanocomposite (RGO@Ag). Several pesticides as well as chlorinated and fluorinated alkyl halides were chosen for this purpose. The composite and the products of degradation were characterized thoroughly by means of various microscopic and spectroscopic techniques. A sequential two-step mechanism involving dehalogenation of the target pollutants by silver nanoparticles followed by adsorption of the degraded compounds onto RGO was revealed. The composite showed unusual adsorption capacity, as high as 1534 mg/g, which facilitated the complete removal of the pollutants. Irrespective of the pollutants tested, a pseudo-second-order rate equation best described the adsorption kinetics. The affinity of the composite manifested chemical differences. The high adsorption capacity and re-usability makes the composite an excellent substrate for purification of water. PMID- 26835897 TI - Photodegradation of diphenylarsinic acid by UV-C light: Implication for its remediation. AB - Diphenylarsinic acid (DPAA) is a major contaminant in environments polluted by chemical weapons and abandoned after World Wars I and II and poses high risks to biota but remediation methods for this contaminant are rare. Here, the photodegradtion of DPAA was studied under high-pressure Hg lamp irradiation. DPAA was degraded completely into inorganic arsenic species in 30 min under UV-C irradiation. The photodegradation of DPAA depended mainly on its direct photolysis through excited-state DPAA. By contrast, the generation of (1)O2 during the photodegradation of DPAA was confirmed by electron paramagnetic resonance (EPR) studies, but (1)O2 had little effect on the photodegradation of DPAA. Phtotodegradation of DPAA was also studied in soil leachates and groundwater and the photolytic rate of DPAA was controlled by the total organic carbon (TOC) content in soil leachates and by the NO3(-) concentration in groundwater. Finally, studies on the effects of common solutes on the photodegradation of DPAA show that Cl(-) can increase the photolytic rate of DPAA by prolonging the lifetime of excited-state DPAA. Moreover, NO3(-), NO2(-), and humic acid (HA) can decrease the photolytic rate of DPAA by suppressing the production of excited-state DPAA. This research shows the detailed mechanism of DPAA photodegradation and provides a new and effective method for DPAA decontamination. PMID- 26835898 TI - Sustaining reactivity of Fe(0) for nitrate reduction via electron transfer between dissolved Fe(2+) and surface iron oxides. AB - The mechanism of the effects of Fe(2+)(aq) on the reduction of NO3(-) by Fe(0) was investigated. The effects of initial pH on the rate of NO3(-) reduction and the Fe(0) surface characteristics revealed Fe(2+)(aq) and the characteristics of minerals on the surface of Fe(0) played an important role in NO3(-) reduction. Both NO3(-) reduction and the decrease of Fe(2+)(aq) exhibited similar kinetics and were promoted by each other. This promotion was associated with the types of the surface iron oxides of Fe(0). Additionally, further reduction of NO3(-) produced more surface iron oxides, supplying more active sites for Fe(2+)(aq), resulting in more electron transfer between Fe(2+) and surface iron oxides and a higher reaction rate. Using the isotope specificity of (57)Fe Mossbauer spectroscopy, it was verified that the Fe(2+)(aq) was continuously converted into Fe(3+) oxides on the surface of Fe(0) and then converted into Fe3O4 via electron transfer between Fe(2+) and the pre-existing surface Fe(3+) oxides. Electrochemistry measurements confirmed that the spontaneous electron transfer between the Fe(2+) and structural Fe(3+) species accelerated the interfacial electron transfer between the Fe species and NO3(-). This study provides a new insight into the interaction between Fe species and contaminants and interface electron transfer. PMID- 26835899 TI - Increased distractibility to own name in psychotic patients with ideas and delusions of reference. AB - INTRODUCTION: This study examined the relationship between ideas and delusions of reference (I/DOR) and attentional shift to a self-referential stimulus (subject's own name, SON). METHODS: Psychotic patients with I/DOR (n = 20) and without I/DOR (n = 17) matched for age and education were tested for attentional shift to SON embedded in a background voice clip presented binaurally when engaging in an attention-demanding task (computerised Stroop task). Reaction time and accuracy in Stroop tasks with and without embedded SON were measured. I/DOR severity, other positive symptoms, negative symptoms and cognitive performance were assessed. RESULTS: There was significant interaction between conditions (Stroop tasks with and without SON) and groups (patients with and without I/DOR) on reaction time (F(1,32) = 4.22, p = .05). Simple main effects showed a significant mean difference in reaction time between conditions in patients with I/DOR (107.7 milliseconds, p = .001) but not in those without (5.8 milliseconds, p = .86). Within-subject difference in reaction time correlated with I/DOR severity scores (r = .33-.52, range; p < .05) and remained significant after controlling for other clinical and cognitive variables. CONCLUSIONS: The significant interaction and simple main effect suggest that I/DOR are associated with a heightened attentional shift to SON. The SON paradigm can potentially be developed into a neurocognitive parameter of I/DOR. However, the lack of non-self stimuli in the SON paradigm limits the interpretation on whether I/DOR are associated with general or specific distractibility related to self-referential information and further studies are warranted. PMID- 26835900 TI - Morpho peleides butterfly wing imprints as structural colour stamp. AB - This study presents the replication of a color-causing nanostructure based on the upper laminae of numerous cover scales of Morpho peleides butterfly wings and obtained solely by imprinting their upper-wing surfaces. Our results indicate that a simple casting technique using a novel integrated release agent can obtain a large positive replica using negative imprints via Polyvinylsiloxane. The developed method is low-tech and high-yield and is thus substantially easier and less expensive than previous methods. The microstructures were investigated with light microscopy, the nanostructures with both scanning and transmission electron microscopy, and the reflections with UV visible spectrometry. The influence of the release agent and the quality of the master stamp were determined by comparing measurements of the cover-scale sizes and their chromaticity values obtained by their images and with their positive imprints. The master stamp provided multiple positive replicas up to 3 cm(2) in just 1 h with structural coloration effects visible to the naked eye. Thus, the developed method proves the accuracy of the replicated nanostructure and its potential industrial application as a color-producing nanostamp. PMID- 26835901 TI - Have We Reached the Limits With Regard to Amino Acid/Protein Intakes in Preterm Infants? PMID- 26835902 TI - Fatty Acid Composition in Feeds and Plasma of Canadian Premature Infants. AB - OBJECTIVES: The objective of the present exploratory study was to investigate how the fatty acid (FA) composition of different food sources for preterm infants including breast milk (BM), formula (F), human milk fortifiers (HMFs), and total parenteral nutrition (TPN) impacted preterm infant's plasma FA. The associations between FA content of plasma with antioxidant enzyme activity and cognition were also evaluated. METHODS: Thirty-two premature infants were included in the present study. Five different feeds (BM, F, BM + F, BM + HMF, and TPN) were provided. Foods and preterm infant plasma samples were collected at the same time on the same day biweekly where possible. Separation and identification of the plasma and food FA methyl esters were performed by gas-liquid chromatography. Antioxidant enzymes were measured. The Bayley Scale of Infant Development version III was used to evaluate cognition. RESULTS: In food sources, BM contained significantly lower stearic acid (C18:0) (P < 0.05), oleic acid (C18:1n9) (P < 0.01), linoleic acid (C18:2n6) (P < 0.01), alpha-linoleic acid (C18:3n3) (P < 0.01), and arachidonic acid (C20:4n6) (P < 0.05) compared with the F. Palmitic acid (C16:0) was significantly higher (P < 0.05) in the BM + HMF compared with the BM. Stearic acid (C18:0) was significantly higher (P < 0.05) in the BM + F and BM + HMF compared with the BM. In the plasma lauric acid (C12:0) (P < 0.05) and myristic acid (C14:0) (P < 0.001) were higher in the BM-fed babies compared with the F-fed or TPN-recipient groups. Antioxidant enzymes, activities and cognition scores did not differ by feeding groups, however the study may not have been powered to detect these differences. CONCLUSIONS: The type, and therefore quality, of fatty acids is an important consideration when selecting what is fed to premature infants because differences in feed fatty acids were seen in some plasma fatty acids in the study. PMID- 26835903 TI - Infliximab-Associated Immunomediated Hepatitis in Children With Inflammatory Bowel Disease. AB - Infliximab (IFX) is commonly used to induce and maintain remission in inflammatory bowel disease (IBD). We report the first 2 cases of children with ulcerative colitis who had normal liver transaminases before IFX and were diagnosed with immunomediated hepatitis after IFX induction. Both the cases had negative antibodies for antinuclear, smooth muscle, and liver kidney microsome, with 1 patient having positive autoimmune serology (dsDNA) and overlap primary sclerosing cholangitis. IFX was discontinued and transaminases normalized without steroid administration. Clinicians treating pediatric patients with IBD with IFX should be aware of IFX immunomediated hepatitis. This phenomenon is previously reported in adult patients with IBD. To our knowledge, these are the first cases reported in pediatric patients with IBD. PMID- 26835905 TI - Comparison of Recommendations in Clinical Practice Guidelines for Acute Gastroenteritis in Children. AB - OBJECTIVE: Acute gastroenteritis (AGE) is a major cause of child mortality and morbidity. This study aimed at systematically reviewing clinical practice guidelines (CPGs) on AGE to compare recommendations and provide the basis for developing single universal guidelines. METHODS: CPGs were identified by searching MEDLINE, Cochrane-Library, National Guideline Clearinghouse and Web sites of relevant societies/organizations producing and/or endorsing CPGs. RESULTS: The definition of AGE varies among the 15 CPGs identified. The parameters most frequently recommended to assess dehydration are skin turgor and sunken eyes (11/15, 73.3%), general appearance (11/15, 66.6%), capillary refill time, and mucous membranes appearance (9/15, 60%). Oral rehydration solution is universally recognized as first-line treatment. The majority of CPGs recommend hypo-osmolar (Na 45-60 mmol/L, 11/15, 66.6 %) or low-osmolality (Na 75 mmol/L, 9/15, 60%) solutions. In children who fail oral rehydration, most CPGs suggest intravenous rehydration (66.6%). However, nasogastric tube insertion for fluid administration is preferred according by 5/15 CPGs (33.3%). Changes in diet and withdrawal of food are discouraged by all CPGs, and early refeeding is strongly recommended in 13 of 15 (86.7%). Zinc is recommended as an adjunct to ORS by 10 of 15 (66.6%) CPGs, most of them from low-income countries. Probiotics are considered by 9 of 15 (60%) CPGs, 5 from high-income countries. Antiemetics are not recommended in 9 of 15 (60%) CPGs. Routine use of antibiotics is discouraged. CONCLUSIONS: Key recommendations for the management of AGE in children are similar in CPGs. Together with accurate review of evidence-base this may represent a starting point for developing universal recommendations for the management of children with AGE worldwide. PMID- 26835904 TI - Plasma Cytokeratin-18 Level As a Novel Biomarker for Liver Fibrosis in Children With Nonalcoholic Fatty Liver Disease. AB - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the obesity epidemic and affects approximately 10% of children in the US. The presence of hepatic fibrosis may be the most important factor in determining the prognosis of NAFLD. Noninvasive methods to identify the presence of fibrosis in children with NAFLD are greatly needed. Hepatocyte apoptosis activates hepatic stellate cells and plays a central role in fibrosis progression in NAFLD. The aim of the present study was to evaluate the use of plasma cytokeratin-18 (CK18) fragment levels, a marker of hepatocyte apoptosis, as a noninvasive biomarker in detecting liver fibrosis in pediatric NAFLD. METHODS: Consecutive children with biopsy-proven NAFLD were included and blood samples and anthropometric measurements were collected at the time of the biopsy. NAFLD activity score was calculated (0-8) and fibrosis stage was scored (0-4). We measured plasma CK18 levels using the M30-Apoptosense enzyme-linked immunosorbent assay kit. RESULTS: A total of 201 subjects were enrolled in the study. The mean age was 10.7 +/- 2.5 years, and 37 % were boys. Sixty-eight percent of the patients had any fibrosis, with 56% having F1, 6% having F2, and 6 % having F3. CK18 levels were found to be significantly higher in subjects with any fibrosis compared with those without fibrosis (304.6 +/- 124.8 vs 210.4 +/- 70.9, P < 0.001). CK18 level revealed good accuracy for prediction of any fibrosis (F1-F3) with AUROC of 0.75. Multivariate logistic regression was performed to assess whether CK18 in combination with another clinical factor could improve accuracy of prediction of fibrosis. Together, CK18 with waist circumference percentile generated an area under the receiver operating characteristics curve of 0.842 for prediction of any fibrosis. CONCLUSIONS: CK18 is a promising noninvasive biomarker for fibrosis in NAFLD in children. A fibrosis prediction model that includes CK18 and waist circumference percentile should be validated in other populations. PMID- 26835906 TI - Paediatric Crohn Disease: Disease Activity and Growth in the BELCRO Cohort After 3 Years Follow-up. AB - OBJECTIVE: The Belgian registry for paediatric Crohn disease (BELCRO) cohort is a prospective, multicentre registry for newly diagnosed paediatric patients with Crohn disease (CD) (<18 years) recruited from 2008 to 2010 to identify predictive factors for disease activity and growth. METHODS: Data from the BELCRO database were evaluated at diagnosis, 24 and 36 months follow-up. RESULTS: At month 36 (M36), data were available on 84 of the 98 patients included at diagnosis. Disease activity evolved as follows: inactive 5% to 70%, mild 19% to 24%, and moderate to severe 76% to 6%. None of the variables such as age, sex, diagnostic delay, type of treatment, disease location, disease activity at diagnosis, and growth were associated with disease activity at M36. Paediatricians studied significantly less patients with active disease at M36 compared with adult physicians. Sixty percent of the patients had biologicals as part of their treatment at M36. Adult gastroenterologists initiated biologicals significantly earlier. They were the only factor determining biologicals' initiation, not disease location or disease severity at diagnosis. Median body mass index (BMI) z score evolved from -0.97 (range -5.5-2.1) to 0.11 (range -3.4-2) and median height z score from -0.15 (range -3.4-1.6) to 0.12 (range -2.3-2.3) at M36. None of the variables mentioned above influenced growth over time. CONCLUSIONS: Present treatment strategies lead to good disease control in the BELCRO cohort after 3 years. Logistic regression analysis did not show any influence of disease location or present treatment strategy on disease activity and growth, but patients under paediatric care had significantly less severe disease at M36. PMID- 26835907 TI - Congenital Sodium Diarrhea: A Form of Intractable Diarrhea, With a Link to Inflammatory Bowel Disease. AB - Congenital diarrheal disorders (CDDs) represent a group of challenging clinical conditions for pediatricians because of the severity of the presentation and the broad range of possible differential diagnoses. CDDs arise from alterations in the transport of nutrients and electrolytes across the intestinal mucosa, from enterocyte and enteroendocrine cell differentiation and/or polarization defects, and from the modulation of the intestinal immune response. Advances were made recently in deciphering the etiology and pathophysiology of one of these disorders, congenital sodium diarrhea (CSD). CSD refers to an intractable diarrhea of intrauterine onset with high fecal sodium loss. CSD is clinically and genetically heterogeneous. A syndromic form of CSD features choanal and intestinal atresias as well as recurrent corneal erosions. Small bowel histology frequently detects an epithelial "tufting" dysplasia. It is autosomal recessively inherited, and caused by SPINT2 mutations. The nonsyndromic form of CSD can be caused by dominant activating mutations in GUCY2C, encoding intestinal receptor guanylate cyclase C (GC-C), and by autosomal recessive SLC9A3 loss-of-function mutations. SLC9A3 encodes Na/H antiporter 3, the major intestinal brush border Na/H exchanger, and a downstream target of GC-C. A number of patients with GUCY2C and SLC9A3 mutations developed inflammatory bowel disease. Both the number of recognized CDD forms as well as the number of underlying disease genes are gradually increasing. Knowledge of these CDD genes enables noninvasive, next generation gene panel-based testing to facilitate an early diagnosis in CDD. Primary Na/H antiporter 3 and GC-C malfunction is implicated as a predisposition for inflammatory bowel disease in subset of patients. PMID- 26835908 TI - Assessment of Endothelial Dysfunction With Adhesion Molecules in Patients With Celiac Disease. AB - OBJECTIVES: Celiac disease (CD) is a systemic immune disorder. We assessed serum levels of adhesion molecules as a marker of endothelial dysfunction in patients with CD at first diagnosis and in those on a gluten-free diet. METHODS: Sixty five patients with CD (mean age 6.74 +/- 4.6 years) and 51 age- and sex-matched control patients participated in the present case-controlled, prospective clinical study. Serum levels of vascular adhesion molecule-1, intercellular adhesion molecule-1, endothelial selectin, vascular endothelial cadherin, high sensitivity C-reactive protein, and homocysteine levels were measured. RESULTS: Average soluble vascular adhesion molecule-1 (CD vs control group: 1320 +/- 308 vs 1120 +/- 406 ng/mL, P = 0.006), soluble intercellular adhesion molecule-1 (336 +/- 99 vs 263 +/- 67 ng/mL, P = 0.025), and soluble endothelial selectin (113.9 +/- 70 vs 76.9 +/- 32 ng/mL, P = 0.007) levels were significantly higher in cases of newly diagnosed CD than in the control group. Soluble vascular adhesion molecule-1 (1050 +/- 190 ng/mL) and soluble endothelial selectin (68.7 +/- 45 ng/mL) levels in patients with CD, who were fully compliant with a gluten-free diet, were significantly lower than that in those newly diagnosed as having CD (P = 0.003 and P = 0.0012, respectively). CONCLUSIONS: These results show that serum adhesion molecule levels are higher in patients with CD. Some of the risks associated with endothelial dysfunction may be related to CD and these risks can be reduced with an appropriate and fully controlled diet. PMID- 26835909 TI - Morphological and Functional Assessment of Oesophageal Mucosa Integrity in Children With Cystic Fibrosis. AB - OBJECTIVES: The aim of the study was to investigate morphological and functional characteristics of oesophageal epithelial barrier in children with cystic fibrosis (CF) with or without gastro-oesophageal reflux disease (GORD) in comparison to healthy controls. METHODS: Oesophagogastroduodenoscopy with oesophageal biopsies and combined oesophageal multichannel intraluminal impedance pH monitoring was performed in 17 children with CF (CFtot) with (CFgord) or without GORD (CFnorm). Histological combined severity score was calculated and widths of spaces between epithelial cells were measured. Basal impedance value was used to assess functional integrity of epithelial barrier. Results of each investigation were compared with a group of children without oesophageal disease. RESULTS: CFtot, but also CFnorm, had more severe pathohistological changes included in the compound severity score than controls (0.75 +/- 0.32 and 0.75 +/- 0.20 vs 0.27 +/- 0.25; P < 0.001 and P = 0.001, respectively). They also had more dilated intercellular spaces (2.6 MUm +/- 0.6 and 2.7 MUm +/- 0.5 vs 1.9 MUm +/- 0.2; P = 0.001 and P < 0.001, respectively). Baseline impedance values between proximal and distal pairs of electrodes were significantly lower in CFtot (2876 Omega +/- 484, 2590 Omega +/- 1013) and also in CFnorm (2922 Omega +/- 363, 2844 Omega +/- 457) than in controls (3703 Omega +/- 859, 3753 Omega +/- 1070) (P = 0.012 and P = 0.002; and P = 0.027 and P = 0.005, respectively). The treatment of CFgord with proton pump inhibitor increased, but did not normalise the baseline impedance values (2860 Omega +/- 560 to 3355 Omega +/- 750 and 2178 Omega +/- 1564 to 3057 Omega +/- 594). CONCLUSIONS: Children with CF had morphological and functional changes of oesophageal mucosal integrity even in the absence of GORD. PMID- 26835910 TI - Quality of community-based day centre services for people with psychiatric disabilities: psychometric properties of the Quality in Psychiatric Care - Daily Activities (QPC-DA). AB - BACKGROUND/AIMS: The aim of the present study was to test the psychometric properties and dimensionality of the instrument Quality in Psychiatric Care - Daily Activities (QPC-DA) and to briefly describe the day centre attendees' perception of the quality at community-based day centre services. METHODS: A sample of 218 attendees from 14 community-based day centre services in seven municipalities in Sweden participated in the study. RESULTS: Confirmatory factor analysis revealed that the QPC-DA consists of six dimensions and has a factor structure that to a large extent corresponds to that found in other studies of quality in psychiatric care settings, such as inpatient, outpatient, forensic inpatient, and housing support for people with psychiatric disabilities. The internal consistency of the factors was satisfactory and thus the QPC-DA showed adequate psychometric properties. The attendees' ratings of quality of community based day centre services were generally high. The highest rating was for the encounter dimension and the lowest for the participation and the secluded environment dimensions, indicating areas for improvement. CONCLUSION/SIGNIFICANCE: The QPC-DA includes important aspects of the attendees' assessment of quality of community-based day centre services and offers a simple and inexpensive way to evaluate quality from their perspective. PMID- 26835913 TI - Application of the harmonic star method in photoelastic separation of principal stresses. AB - This paper deals with automation of an experiment process by means of photoelasticity on the condition that only information which was previously collected by identification of isochromatic fringes is used. The analysis of this issue pointed to Poisson's and Laplace's equations. These equations were solved through the harmonic star method. The automation of an experiment was based on the development of a noncommercial program for processing of data which had been collected during photoelastic measurements. In addition, the program was used for verification of these measurements and comparison of measurement outcomes with results which were gained by the finite element method (FEM). Such a program enabled us to measure stresses in a certain point of the examined surface and, at the same time, separate these stresses, that is, determine the magnitude of individual stresses. A data transfer medium-a camera-was used to transfer the picture of isochromatic fringes directly into a computer. The chosen procedure of solving and evaluating the experiment provided us with reliable outcomes comparable to results gained by FEM. PMID- 26835912 TI - Designed Functional Systems for High-Performance Lithium-Ion Batteries Anode: From Solid to Hollow, and to Core-Shell NiCo2O4 Nanoparticles Encapsulated in Ultrathin Carbon Nanosheets. AB - Binary metal oxides have been considered as ideal and promising anode materials, which can ameliorate and enhance the electrochemical performances of the single metal oxides, such as electronic conductivity, reversible capacity, and structural stability. In this research, we report a rational method to synthesize some novel sandwich-like NiCo2O4@C nanosheets arrays for the first time. The nanostructures exhibit the unique features of solid, hollow, and even core-shell NiCo2O4 nanoparticles encapsulated inside and a graphitized carbon layers coating outside. Compared to the previous reports, these composites demonstrate more excellent electrochemical performances, including superior rate capability and excellent cycling capacity. Therefore, the final conclusion would be given that these multifarious sandwich-like NiCo2O4@C composites could be highly qualified candidates for lithium-ion battery anodes in some special field, in which good capability and high capacity are urgently required. PMID- 26835914 TI - Compressed sensing snapshot spectral imaging by a regular digital camera with an added optical diffuser. AB - We propose a spectral imaging method that allows a regular digital camera to be converted into a snapshot spectral imager by equipping the camera with a dispersive diffuser and with a compressed sensing-based algorithm for digital processing. Results of optical experiments are reported. PMID- 26835911 TI - The CXCL10/CXCR3 axis promotes cardiac microvascular endothelial cell migration via the p38/FAK pathway in a proliferation-independent manner. AB - CXCL10 is a chemokine with potent chemotactic activity for immune and non-immune cells expressing its receptor CXCR3. Previous studies have demonstrated that CXCL10 is involved in myocardial infarction. However, the role of CXCL10 in cardiac microvascular endothelial cell (CMEC) regulation and related mechanisms remains unclear. In this study, we investigated the effects of CXCL10 on the CMEC migration and explored its potential molecular mechanism by wound healing, cell proliferation and viability analysis. Furthermore, migration-related signaling pathways, including FAK, Erk, p38 and Smad, were examined by Western blotting. We found that CXCL10 significantly promotes CMEC migration under normal conditions and during hypoxia/ischemia. However, no significant differences in CMEC proliferation and viability were observed with or without CXCL10 treatment. CXCL10-mediated CMEC migration was greatly blocked by treatment with an anti CXCR3 antibody. Although CXCL10 treatment promoted phosphorylation and activation of the FAK, Erk, and p38 pathways during hypoxia/ischemia, CXCL10-mediated CMEC migration was significantly blocked by p38 and FAK inhibitors, but not by an Erk inhibitor. Furthermore, CXCL10-mediated FAK activation was suppressed by the p38 inhibitor. These findings indicated that the CXCL10/CXCR3 pathway promotes the migration of CMECs under normal conditions and during hypoxia/ischemia in a proliferation-independent manner, at least in part, through regulation of the p38/FAK pathways. PMID- 26835915 TI - Influence of absorption on stability of terahertz difference frequency generation. AB - This work presents numerical studies of the stability feature of terahertz difference frequency generation (THz-DFG) with a ZnGeP(2) crystal using two pump wavelengths. We found that the maximum output of a THz wave is located in the unstable output region because of the competitive equilibrium between the absorption and the gain. Furthermore, the output stability is dependent on the pump stability. Different from the results at the pump wavelength of 9.588 MUm, there is neither an appropriate stable output region nor gain saturation region at the pump wavelength of 1.064 MUm for a larger absorption coefficient. This work demonstrates that the stable output region of the THz wave is difficult to obtain when the pump absorption is excessively large in DFG. PMID- 26835916 TI - Nanoscale three-dimensional single particle tracking by light-sheet-based double helix point spread function microscopy. AB - The double-helix point spread function (DH-PSF) microscopy has become an essential tool for nanoscale three-dimensional (3D) localization and tracking of single molecules in living cells. However, its localization precision is limited by fluorescent contrast in thick samples because the signal-to-noise ratio of the system is low due to the inherent low transfer function efficiency and background fluorescence. Here we combine DH-PSF microscopy with light-sheet illumination to eliminate out-of-focus background fluorescence for high-precision 3D single particle tracking. To demonstrate the capability of the method, we obtain the single fluorescent bead image with light-sheet illumination, with three dimensional localization accuracy better than that of epi-illumination. We also show that the single fluorescent beads in agarose solution can be tracked, which demonstrates the possibility of our method for the study of dynamic processes in complex biological specimens. PMID- 26835917 TI - Automated segmentation of subretinal layers for the detection of macular edema. AB - Macular edema (ME) is considered as one of the major indications of proliferative diabetic retinopathy and it is commonly caused due to diabetes. ME causes retinal swelling due to the accumulation of protein deposits within subretinal layers. Optical coherence tomography (OCT) imaging provides an early detection of ME by showing the cross-sectional view of macular pathology. Many researchers have worked on automated identification of macular edema from fundus images, but this paper proposes a fully automated method for extracting and analyzing subretinal layers from OCT images using coherent tensors. These subretinal layers are then used to predict ME from candidate images using a support vector machine (SVM) classifier. A total of 71 OCT images of 64 patients are collected locally in which 15 persons have ME and 49 persons are healthy. Our proposed system has an overall accuracy of 97.78% in correctly classifying ME patients and healthy persons. We have also tested our proposed implementation on spectral domain OCT (SD-OCT) images of the Duke dataset consisting of 109 images from 10 patients and it correctly classified all healthy and ME images in the dataset. PMID- 26835918 TI - Hyperspectral band selection based on a variable precision neighborhood rough set. AB - Band selection is a well-known approach for reducing dimensionality in hyperspectral images. We propose a band-selection method based on the variable precision neighborhood rough set theory to select informative bands from hyperspectral images. A decision-making information system was established by hyperspectral data derived from soybean samples between 400 and 1000 nm wavelengths. The dependency was used to evaluate band significance. The optimal band subset was selected by a forward greedy search algorithm. After adjusting appropriate threshold values, stable optimized results were obtained. To assess the effectiveness of the proposed band-selection technique, two classification models were constructed. The experimental results showed that admitting inclusion errors could improve classification performance, including band selection and generalization ability. PMID- 26835919 TI - Influence of the eigenmode polarization deviation on the output Sagnac frequency difference in nonplanar ring resonators. AB - We present a theoretical model to quantitatively analyze the influence of the eigenmode polarization deviation (described with ellipticity parameter) on the output Sagnac frequency difference in two nonplanar ring resonators with different mirror arrangements. The theoretical and numerical analysis results prove that the deviation of the eigenmode polarization from the ideally circular polarized state will produce a drop of the output Sagnac frequency difference. Furthermore, for the identical ellipticity parameter and incident angles, the decline values along the rotation axis A(2) is more obvious than that along axis A(1). In other words, these results show that the output Sagnac frequency difference can be improved effectively by restraining the eigenmode polarization deviation quantitatively and that these analysis findings are useful for designing and optimizing the structure of laser gyroscopes with super-high precision. PMID- 26835920 TI - Fiber-coupled diode-laser sensors for calibration-free stand-off measurements of gas temperature, pressure, and composition. AB - A fiber-coupled near-infrared diode-laser sensor for stand-off measurements of gas temperature, pressure, and composition is presented. This sensor utilizes a fiber bundle with six multimode catch fibers surrounding one single-mode pitch fiber to transmit and receive backscattered laser light in a handheld transmitter/receiver. Scanned-wavelength-modulation spectroscopy with 1f normalized 2f-detection and fast (80-200 kHz) wavelength modulation were used to provide calibration-free measurements and reduce the influence of spurious cavity noise formed by the overlapping transmitted and reflected laser light. Demonstrations include two-color measurements of temperature, pressure, and H(2)O near 1.4 MUm in a propane flame at 2 kHz (SNR=200) and measurements of CH(4) near 1.65 MUm (SNR=20 to 1500) at stand-off distances of 15 cm and 10 m, respectively. The fraction of photons collected ranged from 10(4) to 1 parts per million at stand-off distances from 10 cm to 10 m, respectively, and is similar for aluminum and paper reflectors. PMID- 26835921 TI - Surface modification of optical materials with hydrogen plasma for fabrication of Bragg gratings. AB - We investigate the hydrogen plasma process as a route for creating Bragg gratings (BGs) on optoelectronic materials such as undoped lithium niobate (LiNbO(3)), proton-exchanged LiNbO(3), and soda-lime glass. Photopatterns (periodic modulations, Lambda=323-2000 nm) were created on those substrates and the hydrogen plasma process was investigated for its ability to transfer the microstructures and the underlying mechanisms involved in this process. The diffraction efficiency and surface topology of the BG were characterized, as well as the optical properties of corresponding bulk materials undergoing the same plasma treatment. It is shown that the hydrogen plasma treatment changes the complex refractive index and modifies the surface topology with a volume expansion in the near-surface region, and both features are connected to the appearance of structural defects in the materials. The hydrogen plasma offers unique flexibility and advantages that can be explored for the fabrication of integrated photonic components. PMID- 26835922 TI - Prospective effect in dispersion properties of photonic crystal fibers by selective water-filling of holes. AB - Based on a simple but accurate semivectorial solution of Helmholtz's equation by the finite difference method devised with a mode-field convergence technique, we have shown an interesting and significant effect showing an almost ultraflat zero group velocity dispersion in photonic crystal fiber when the holes of the first ring of the fiber are filled with water. Crosschecking our results with earlier results involving a deeply involved multipole method for the central core of photonic crystal fiber filled with water and fused silica, our observation in the case of filling the first ring holes with water reveals potential information in studies of supercontinuum generation. PMID- 26835923 TI - Four-color laser diagnostics for Z-pinch and laser-produced plasma. AB - Four-color laser diagnostics were developed for Z-pinch and laser plasma at the 1 MA pulsed power generator. Four harmonics of the Nd:YAG laser at wavelengths of 1064, 532, 266, and 213 nm were produced during the cascade conversion in three nonlinear crystals and propagated together in one beampath. Deep UV probing allows better penetration of the dense plasma. Laser probing at four wavelengths allows observation of plasma in a wide range of densities in one shot of the diagnostic laser. Examples of four-color laser shadowgraphy and interferometry of the wire-array load and laser plasma interaction are presented and discussed. PMID- 26835924 TI - Efficiency of different methods of extra-cavity second harmonic generation of continuous wave single-frequency radiation. AB - This work presents for the first time to the best of our knowledge a comparative efficiency analysis among various techniques of extra-cavity second harmonic generation (SHG) of continuous-wave single-frequency radiation in nonperiodically poled nonlinear crystals within a broad range of power levels. Efficiency of nonlinear radiation transformation at powers from 1 W to 10 kW was studied in three different configurations: with an external power-enhancement cavity and without the cavity in the case of single and double radiation pass through a nonlinear crystal. It is demonstrated that at power levels exceeding 1 kW, the efficiencies of methods with and without external power-enhancement cavities become comparable, whereas at even higher powers, SHG by a single or double pass through a nonlinear crystal becomes preferable because of the relatively high efficiency of nonlinear transformation and fairly simple implementation. PMID- 26835925 TI - Three-dimensional ray-tracing model for the study of advanced refractive errors in keratoconus. AB - We propose a numerical three-dimensional (3D) ray-tracing model for the analysis of advanced corneal refractive errors. The 3D modeling was based on measured corneal elevation data by means of Scheimpflug photography. A mathematical description of the measured corneal surfaces from a keratoconus (KC) patient was used for the 3D ray tracing, based on Snell's law of refraction. A model of a commercial intraocular lens (IOL) was included in the analysis. By modifying the posterior IOL surface, it was shown that the imaging quality could be significantly improved. The RMS values were reduced by approximately 50% close to the retina, both for on- and off-axis geometries. The 3D ray-tracing model can constitute a basis for simulation of customized IOLs that are able to correct the advanced, irregular refractive errors in KC. PMID- 26835926 TI - Broadband mid-infrared fiber optical parametric oscillator based on a three-hole suspended-core chalcogenide fiber. AB - A mid-infrared fiber optical parametric oscillator is proposed and designed based on a three-hole As(2)S(5) suspended-core fiber (SCF). The eigenmodes of the SCF are depicted and the pump condition for single-mode operation is analyzed. The zero-dispersion wavelength is shifted to 2 MUm by tuning the core diameter of the SCF. Using the degenerate four-wave mixing coupled-wave equations, a tuning range of the idler wavelength from 2 to 5 MUm and a maximum conversion efficiency of 19% are numerically predicted in a 0.1-m-long SCF pumped by a 2.7 W thulium-doped fiber laser. PMID- 26835927 TI - Measuring method of diffraction efficiency for plane grating based on Fourier spectral technology. AB - A traditional double monochromatic measurement instrument of diffraction efficiency for a plane grating involves two major problems: one is the differences of output spectrum bandwidths during measurement of a standard reflection mirror and the tested grating; the other is overlapping of diffracted spectra, which influence testing accuracy of diffraction efficiency. In this paper, a new measuring method of diffraction efficiency based on Fourier spectral technology is presented. The mathematical model of diffraction efficiency is first deduced and then verified by ray tracing and Fourier optics simulation. The influences of the moving cube corner's tilt error, lateral shift error, and maximal moving distance error on the measurement accuracy are analyzed in detail. The analyses provide theoretical references for designing diffraction efficiency instruments. Compared with the traditional diffraction efficiency measurement instrument with double monochromator structure, our method not only improves the measurement accuracy of diffraction efficiency but also has the advantage of high luminous flux, high spectral resolution, multiwavelength measurement in mean time, and high wavenumber accuracy. PMID- 26835928 TI - Propagation of electromagnetic fields between non-parallel planes: a fully vectorial formulation and an efficient implementation. AB - The propagation of electromagnetic fields between non-parallel planes based on a spectrum-of-plane-wave analysis is discussed and formulations for an efficient numerical implementation are presented in detail. It is shown that with the help of interpolation techniques, the numerical implementation can be done with the standard uniform fast Fourier transform (FFT) of easy access. Different interpolation techniques are numerically examined, and it turns out that the use of cubic interpolation, together with the uniform FFT, brings both significantly increased computational efficiency and high simulation accuracy. Apart from the aspect of computational efficiency, all formulations in this work are generalized in a fully vectorial manner in comparison to previous works. PMID- 26835929 TI - Dispersed fringe sensor for the Giant Magellan Telescope. AB - The Giant Magellan Telescope (GMT) consists of seven 8.365 m segments, with gaps of 0.345 m between adjacent segments. A unique challenge for GMT lies in phasing the segments and, in particular, how to measure segment piston optically while the telescope is in science operation. In this paper, we present a dispersed fringe sensor (DFS) to make these measurements using a novel algorithm. We show that using four off-axis DFSs operating at J-band with 10 ms exposures, we are able to measure segment piston to the required 50 nm accuracy every 30 s with over 90% sky coverage. PMID- 26835930 TI - Effect of pulse duration on the acoustic frequency emissions during the laser induced breakdown of atmospheric air. AB - Acoustic shock waves (ASWs) in the frequency range of 30-120 kHz generated during laser-induced breakdown (LIB) of ambient air using 7 ns and 30 ps pulse durations are studied. The specific frequency range and peak amplitudes are observed to be different for nanosecond (ns) and picosecond (ps) LIB. The ASW frequencies for ps LIB lie between 90 and 120 kHz with one dominant peak, whereas for ns-LIB, two dominant peaks with frequencies in the 30-70 kHz and 80-120 kHz range are observed. These frequencies are observed to be laser pulse intensity dependent. With increasing energy of ns laser pulses, acoustic frequencies move toward the audible frequency range. The variation in the acoustic parameters, such as peak to-peak pressures, signal energy, frequency and acoustic pulse widths as a function of laser energy, for two different pulse durations are presented in detail and compared. The acoustic emissions are observed to be higher for ns-LIB than ps-LIB, indicating higher conversion efficiency of optical energy into mechanical energy. PMID- 26835931 TI - Wide-range average temperature measurements of convective fluid flows by using a schlieren system. AB - In the schlieren method, the deflection of light by the presence of an inhomogeneous medium is proportional to the gradient of its refractive index. In the presence of temperature variations in a fluid flow, the refraction index is related to the gas density by the Gladstone-Dale constant, which depends on the nature of the gas and the wavelength of light propagating in the medium. The deflection of light in a schlieren system is represented by intensity variations on the observation plane. Then, for a digital camera, the intensity level registered in each pixel depends mainly on the refractive index variation of the medium and exposure time. Therefore, if we regulate the intensity value of each pixel by controlling the exposure time, it is possible to adjust the temperature value measurements. In this way, a specific exposure time of a digital camera allows us to measure a determined range of temperature values. For that reason, in this study we determine the range of temperatures that can be measured with a digital camera for different exposure times. By doing this, a wide range of average temperature value fields can be obtained by summing up the temperature contribution of each exposure time. The basic idea in our approach to measure temperature by using a schlieren system is to relate the intensity level of each pixel in a schlieren image to the corresponding knife-edge position measured at the exit focal plane of the system. Our approach is applied to the measurement of temperature fields of the air convection caused by a heated rectangular metal plate (7.3 cm*12 cm) and a candle flame. We found that the maximum temperature values obtained for exposure times of 31.3, 15.7, 7.9, 3.9, and 2 ms were 67.3 degrees C, 122.6 degrees C, 217.4 degrees C, 364.3 degrees C, and 524.0 degrees C, respectively. PMID- 26835932 TI - Electro-plasmonic 2 * 2 channel-routing switch arranged on a thin-Si-doped metal/insulator/semiconductor/metal structure. AB - Plasmonics as a new field of chip-scale technology is the interesting substrate of this study to propose and numerically investigate a metal/insulator/semiconductor/metal (MISM)-structure 2*2 plasmonic routing switch. As a planar subwavelength arrangement, the presented design has two npn doped side-coupled dual waveguides whose duty is to route the propagating surface plasmon polaritons through the device. Relying on the MISM structure, which has a MOS-like thin-film arrangement of typically 45 nm doped silicon covered by a layer of 8 nm thick HfO(2) gate insulator, the routing configuration is electrically addressed based on the carrier-induced plasma dispersion effects as an external electro-plasmonic switching control. Finite-element-method-conducted electromagnetic simulations are employed to evaluate the switch optical response at telecom wavelength of lambda=1550 nm, due to which the balanced operation measure of extinction ratios larger than 10 dB and insertion losses of around 1.8 dB are obtained for both channels of CROSS and STRAIGHT. Compared with other photonic and plasmonic switching counterparts, this configuration, besides its potential for CMOS compatibility, can be utilized as a high-speed compact building block to sustain higher-speed, more miniaturized, and less consuming electro-optic routing/switching protocols toward complicated optical integrated circuits and systems. PMID- 26835933 TI - Controlling photoluminescent emission from polymer membranes through the creation of local deformation zones. AB - Understanding and optimizing light propagation and extraction in light-emitting systems, such as fluorescent chemical sensors, is important for the production of more efficient sensors. We apply Monte Carlo ray tracing to model the effects of one-dimensional perturbations of film thickness on the luminescent emission (spatial, directional, spectral) of a freestanding transparent polymer film embedded with luminescent chromophores. Such modification not only enhances light extraction but also allows its location and direction to be controlled. Optimization of the deformation geometry allows for a 3.6-fold increase in intensity for a far-field detector. PMID- 26835934 TI - Two particle tracking and detection in a single Gaussian beam optical trap. AB - We have studied in detail the situation wherein two microbeads are trapped axially in a single-beam Gaussian intensity profile optical trap. We find that the corner frequency extracted from a power spectral density analysis of intensity fluctuations recorded on a quadrant photodetector (QPD) is dependent on the detection scheme. Using forward- and backscattering detection schemes with single and two laser wavelengths along with computer simulations, we conclude that fluctuations detected in backscattering bear true position information of the bead encountered first in the beam propagation direction. Forward scattering, on the other hand, carries position information of both beads with substantial contribution from the bead encountered first along the beam propagation direction. Mie scattering analysis further reveals that the interference term from the scattering of the two beads contributes significantly to the signal, precluding the ability to resolve the positions of the individual beads in forward scattering. In QPD-based detection schemes, detection through backscattering, thereby, is imperative to track the true displacements of axially trapped microbeads for possible studies on light-mediated interbead interactions. PMID- 26835935 TI - Third-harmonic generation at the interfaces of a cuvette filled with selected organic solvents. AB - We report on the third-harmonic generation (THG) of tightly focused femtosecond laser pulses at the interfaces of a cuvette filled with organic solvents. Such a system presents four interfaces separating two materials of different refractive indices and third-order nonlinear susceptibilities where the THG takes place because the symmetry around the focus is broken. We selected two cuvettes (silica and B270 crown glass) filled with different organic solvents (acetone, chloroform, and dimethyl sulfoxide) in order to have a variety of interfaces with different linear and nonlinear optical properties. For some of the peaks, the self-focusing modifies the expected cubic power law dependence for THG and as a consequence the four peak profiles may be quite uneven. Although the THG is due to the electronic part of the nonlinear susceptibility, it can suffer from the influence of the self-focusing effect, a Kerr nonlinearity that can have both instantaneous electronic and slow nuclear contributions. This mixture of two distinct third-order nonlinear processes was never considered for such interfaces. All the THG signals could be understood by taking into account the self-focusing effect. Furthermore, the nonlinear refractive indices, n(2), and third-order nonlinear susceptibilities of the solvents, chi((3)), could be determined simultaneously by the THG signals using the cuvette walls as a reference. PMID- 26835936 TI - High electric field measurement using slab-coupled optical sensors. AB - A fiber-optic electric field sensor was developed to measure electric field up to 18 MV/m. The sensor uses resonant coupling between an optical fiber and a nonlinear electro-optical crystal. The sensing system uses high dielectric strength materials to eliminate dielectric breakdown. A postprocessing nonlinear calibration method is developed that maps voltage change to wavelength shift and then converts the wavelength shift to electric field using the transmission spectrum. The nonlinear calibration method is compared against the linear method with electric field pulses having magnitudes from 1.5 to 18 MV/m. PMID- 26835937 TI - Design of a compact and integrated TM-rotated/TE-through polarization beam splitter for silicon-based slot waveguides. AB - A compact and integrated TM-rotated/TE-through polarization beam splitter for silicon-based slot waveguides is proposed and characterized. For the input TM mode, it is first transferred into the cross strip waveguide using a tapered directional coupler (DC), and then efficiently rotated to the corresponding TE mode using an L-shaped bending polarization rotator (PR). Finally, the TE mode for slot waveguide at the output end is obtained with the help of a strip-to-slot mode converter. By contrast, for the input TE mode, it almost passes through the slot waveguide directly and outputs at the bar end with nearly neglected coupling due to a large mode mismatch. Moreover, an additional S-bend connecting the tapered DC and bending PR is used to enhance the performance. Results show that a total device length of 19.6 MUm is achieved, where the crosstalk (CT) and polarization conversion loss are, respectively -26.09 and 0.54 dB, for the TM mode, and the CT and insertion loss are, respectively, -22.21 and 0.41 dB, for the TE mode, both at 1.55 MUm. The optical bandwidth is approximately 50 nm with a CT<-20 dB. In addition, fabrication tolerances and field evolution are also presented. PMID- 26835938 TI - Problems in the application of a null lens for precise measurements of aspheric mirrors. AB - Problems in the application of a null lens for surface shape measurements of aspherical mirrors are discussed using the example of manufacturing an aspherical concave mirror for the beyond extreme ultraviolet nanolithographer. A method for allowing measurement of the surface shape of a sample under study and the aberration of a null lens simultaneously, and for evaluating measurement accuracy, is described. Using this method, we made a mirror with an aspheric surface of the 6th order (i.e., the maximum deviation from the best-fit sphere is 6.6 MUm) with the parameters of the deviations from the designed surface PV=5.3 nm and RMS=0.8 nm. An approximation of the surface shape was carried out using Zernike polynomials {Z(n)(m)(r,phi),m+n<=36}. The physical limitations of this technique are analyzed. It is shown that for aspheric measurements to an Angstrom accuracy, one needs to have a null lens with errors of less than 1 nm. For accurate measurements, it is necessary to establish compliance with the coordinates on the sample and on the interferogram. PMID- 26835940 TI - Proximity-effect correction for 3D single-photon optical lithography. AB - A proximity-effect-correction (PEC) algorithm for three-dimensional (3D) single photon gray-scale photolithography is proposed and numerically analyzed in this paper. The gray-scale dose assigned to every point within the photoresist volume is optimized to guarantee that the fabricated 3D patterns are as close to the designed patterns as possible. PEC optimizations for 3D woodpile geometries using low and high absorption photoresist are simulated. Spatial resolution of the proposed PEC algorithm is numerically studied. We also investigated the efficacy of our algorithm on a variety of related 3D geometries. PMID- 26835939 TI - Polarimetric imaging and retrieval of target polarization characteristics in underwater environment. AB - Polarized light fields contain more information than simple irradiance and such capabilities provide an advanced tool for underwater imaging. The concept of the beam spread function (BSF) for analysis of scalar underwater imaging was extended to a polarized BSF which considers polarization. The following studies of the polarized BSF in an underwater environment through Monte Carlo simulations and experiments led to a simplified underwater polarimetric imaging model. With the knowledge acquired in the analysis of the polarimetric imaging formation process of a manmade underwater target with known polarization properties, a method to extract the inherent optical properties of the water and to retrieve polarization characteristics of the target was explored. The proposed method for retrieval of underwater target polarization characteristics should contribute to future efforts to reveal the underlying mechanism of polarization camouflage possessed by marine animals and finally to generalize guidelines for creating engineered surfaces capable of similar polarization camouflage abilities in an underwater environment. PMID- 26835941 TI - Sampling and error analysis of radial symmetric interpolation for fast hologram generation. AB - In this paper, we present a fast hologram pattern generation method by radial symmetric interpolation, which exploits concentric redundancy of a point hologram pattern to reduce computational complexity in hologram pattern calculation, and analyze the quality degradation sources in the proposed method. Compared to the analytic method in which phase and amplitude information is directly calculated from a wave equation, in our method a Fresnel zone plate is periodically sampled along a diagonal line and the wave information of a point hologram is calculated by linear interpolation. During these sampling and interpolation processes, the wave information can be modified from the original signal and the reconstruction quality can be degraded compared to the analytic pattern calculation method. The effects of sampling and linear interpolation are investigated in spatial and frequency domains. PMID- 26835942 TI - Microtomography imaging of an isolated plant fiber: a digital holographic approach. AB - This paper describes a method for optical projection tomography for the 3D in situ characterization of micrometric plant fibers. The proposed approach is based on digital holographic microscopy, the holographic capability being convenient to compensate for the runout of the fiber during rotations. The setup requires a telecentric alignment to prevent from the changes in the optical magnification, and calibration results show the very good experimental adjustment. Amplitude images are obtained from the set of recorded and digitally processed holograms. Refocusing of blurred images and correction of both runout and jitter are carried out to get appropriate amplitude images. The 3D data related to the plant fiber are computed from the set of images using a dedicated numerical processing. Experimental results exhibit the internal and external shapes of the plant fiber. These experimental results constitute the first attempt to obtain 3D data of flax fiber, about 12 MUm*17 MUm in apparent diameter, with a full-field optical tomography approach using light in the visible range. PMID- 26835943 TI - Analysis on image expressible region of integral floating. AB - We define the image expressible region where three-dimensional (3D) images can be reconstructed in an integral floating display using ray distribution information. Here, the image expressible and viewing regions of the integral floating system, defined using ray distribution based on ray optics, are analyzed to resolve an image-cropping problem known as the viewing window that is due to the virtual aperture. Two experiments for verifying the image expressible and viewing regions are performed, and the results are presented. The obtained analysis is useful to maximize the viewing properties of integral floating. PMID- 26835944 TI - Realization of real-time interactive 3D image holographic display [Invited]. AB - Realization of a 3D image holographic display supporting real-time interaction requires fast actions in data uploading, hologram calculation, and image projection. These three key elements will be reviewed and discussed, while algorithms of rapid hologram calculation will be presented with the corresponding results. Our vision of interactive holographic 3D displays will be discussed. PMID- 26835945 TI - Fast phase-added stereogram algorithm for generation of photorealistic 3D content. AB - A new phase-added stereogram algorithm for accelerated computation of holograms from a point cloud model is proposed. The algorithm relies on the hologram segmentation, sampling of directional information, and usage of the fast Fourier transform with a finer grid in the spatial frequency domain than is provided by the segment size. The algorithm gives improved quality of reconstruction due to new phase compensation introduced in the segment fringe patterns. The result is finer beam steering leading to high peak intensity and a large peak signal-to noise ratio in reconstruction. The feasibility of the algorithm is checked by the generation of 3D contents for a color wavefront printer. PMID- 26835946 TI - See-through integral imaging display with background occlusion capability. AB - Background occlusion capability is provided to a flat-panel-type integral imaging display that has a transparent screen and can superimpose three-dimensional (3D) images on real scenes. A symmetric integral imaging system that comprises two integral imaging systems connected by an additional lens array, is proposed. Elementary images are displayed on a flat-panel display on one integral imaging system to generate 3D images, and the occlusion mask patterns are displayed on a flat-panel display on the other integral imaging system to selectively block rays from background scenes. The proposed system was constructed and experimentally verified. PMID- 26835947 TI - Direct inversion of digital 3D Fraunhofer holography maps. AB - Differential Fourier holography (DFH) gives an exact mathematical solution of the inverse problem of diffraction in the Fraunhofer regime. After the first publication [Opt. Express15, 9954 (2007)], DFH was successfully applied in many experiments to obtain amplitude and phase information about two-dimensional images. In this paper, we demonstrate numerically the possibility to apply DFH also for investigation of unknown three-dimensional objects. The first simulation is made for a double-spiral structure plus a line as a reference object. PMID- 26835948 TI - Layered holographic stereogram based on inverse Fresnel diffraction. AB - We propose an efficient algorithm using layered holographic stereogram for three dimensional (3D) computer-generated holograms. The hologram is spatially partitioned into multiple holographic elements (hogels) to provide the occlusion effect and motion parallax by use of multiple viewpoint rendering. Each hogel is calculated with inverse Fresnel diffraction by slicing the viewing frustum according to the depth image. The sliced layers can provide accurate depth cues for reconstruction since the geometric information of the 3D scene is faithfully matched. The algorithm is compatible with computer graphics rendering techniques and robust for holograms with different parameters. When the hogel size equals 1 mm, the signal-to-noise ratio of the diffraction calculation is above 39 dB with a propagation distance longer than 10 mm. Numerical simulations and optical experiments have demonstrated that the proposed method can reconstruct quality 3D images with reduced computational load. PMID- 26835949 TI - Fast point-based method of a computer-generated hologram for a triangle-patch model by using a graphics processing unit. AB - The point-based method and fast-Fourier-transform-based method are commonly used for calculation methods of computer-generation holograms. This paper proposes a novel fast calculation method for a patch model, which uses the point-based method. The method provides a calculation time that is proportional to the number of patches but not to that of the point light sources. This means that the method is suitable for calculating a wide area covered by patches quickly. Experiments using a graphics processing unit indicated that the proposed method is about 8 times or more faster than the ordinary point-based method. PMID- 26835950 TI - Fast calculation method of computer generated hologram animation for viewpoint parallel shift and rotation using Fourier transform optical system. AB - Computer generated hologram (CGH) animations can be made by switching many CGHs on an electronic display. Some fast calculation methods for CGH animations have been proposed, but one for viewpoint movement has not been proposed. Therefore, we designed a fast calculation method of CGH animations for viewpoint parallel shifts and rotation. A Fourier transform optical system was adopted to expand the viewing angle. The results of experiments were that the calculation time of our method was over 6 times faster than that of the conventional method. Furthermore, the degradation in CGH animation quality was found to be sufficiently small. PMID- 26835951 TI - Full-color optical scanning holography with common red, green, and blue channels [Invited]. AB - We propose color optical scanning holography (OSH) that records red, green, and blue (RGB) holograms of real objects by single scanning. The proposed color OSH composes a RGB multiplexing unit, color time-dependent Fresnel zone plate generation unit, scanning unit, space-integrating photodetection unit, and demultiplexing unit. In the proposed color OSH, RGB beams follow a common path from the multiplexing unit to a photodetector, generating an electric current containing the object's complex RGB hologram information. In the demultiplexing unit, the complex RGB holograms are extracted and arranged as a complex color hologram. In experiments, we record the complex color hologram of a three dimensional object composed of RGB transparencies using the color OSH. Numerical reconstruction shows that the recorded hologram contains information about the object's color as well as the diffracted field from the object. PMID- 26835952 TI - 3D touchable holographic light-field display. AB - We propose a new type of 3D user interface: interaction with a light field reproduced by a 3D display. The 3D display used in this work reproduces a 3D light field, and a real image can be reproduced in midair between the display and the user. When using a finger to touch the real image, the light field from the display will scatter. Then, the 3D touch sensing is realized by detecting the scattered light by a color camera. In the experiment, the light-field display is constructed with a holographic screen and a projector; thus, a preliminary implementation of a 3D touch is demonstrated. PMID- 26835953 TI - Electro-optic modulation methods in range-gated active imaging. AB - A time-resolved imaging method based on electro-optic modulation is proposed in this paper. To implement range resolution, two kinds of polarization-modulated methods are designed, and high spatial and range resolution can be achieved by the active imaging system. In the system, with polarization beam splitting the incident light is split into two parts, one of which is modulated with cos(2) function and the other is modulated with sin(2) function. Afterward, a depth map can be obtained from two simultaneously received images by dual electron multiplying charge-coupled devices. Furthermore, an intensity image can also be obtained from the two images. Comparisons of the two polarization-modulated methods indicate that range accuracy will be promoted when the polarized light is modulated before beam splitting. PMID- 26835954 TI - Three-directional motion-compensation mask-based novel look-up table on graphics processing units for video-rate generation of digital holographic videos of three dimensional scenes. AB - A three-directional motion-compensation mask-based novel look-up table method is proposed and implemented on graphics processing units (GPUs) for video-rate generation of digital holographic videos of three-dimensional (3D) scenes. Since the proposed method is designed to be well matched with the software and memory structures of GPUs, the number of compute-unified-device-architecture kernel function calls can be significantly reduced. This results in a great increase of the computational speed of the proposed method, allowing video-rate generation of the computer-generated hologram (CGH) patterns of 3D scenes. Experimental results reveal that the proposed method can generate 39.8 frames of Fresnel CGH patterns with 1920*1080 pixels per second for the test 3D video scenario with 12,088 object points on dual GPU boards of NVIDIA GTX TITANs, and they confirm the feasibility of the proposed method in the practical application fields of electroholographic 3D displays. PMID- 26835955 TI - Estimation of parameters for evaluating subsurface microcracks in glass with in line digital holographic microscopy. AB - In this work, a new method for imaging subsurface damage (SSD) is proposed, which is, to the best of our knowledge, the first application of the in-line digital holographic microscopy (IDHM) to the reconstruction of the subsurface damage in glass. By combination of the in-line arrangement and an objective lens to image the hologram on the CCD surface, the method is characterized by its high resolution in both the lateral and depth directions. Then the three-dimensional reconstruction of the microcracks within the glass was realized by numerically focusing en-face images at different depths, and the sizes of SSD along the transversal and depth directions were estimated. Based on the experimental results, the cracks can be divided into two categories: one is that the cracks begin from the surface of optical elements, the other is totally within the components. To indicate the propagation or development trajectory of the cracks and predict the magnitude of the laser-induced damage threshold, the relative intensity distributions of the light scattered by the cracks compared with the ones without cracks were also reconstructed. In this case all the required parameters for evaluating SSD are obtained with our IDHM system, so that the SSD produced in the manufacturing process can be reduced or removed more easily to optimize the performance of the optical component and extend its lifetime. These results provide the guidance for the optical system design of precision measurements. PMID- 26835957 TI - Dual-wavelength digital holography for 3D particle image velocimetry: experimental validation. AB - A multi-exposure digital in-line hologram of a particle field is recorded by two successive pulses of different wavelengths. During the reconstruction step, each recording can be independently analyzed by selecting a given wavelength. This procedure enables avoiding the superimposition of particle images that may be close to each other. PMID- 26835956 TI - Synthetic aperture in terahertz in-line digital holography for resolution enhancement. AB - Terahertz digital holography is a combination of terahertz technology and digital holography. In digital holography, the imaging resolution is the key parameter in determining the detailed quality of a reconstructed wavefront. In this paper, the synthetic aperture method is used in terahertz digital holography and the in-line arrangement is built to perform the detection. The resolved capability of previous terahertz digital holographic systems restricts this technique to meet the requirement of practical detection. In contrast, the experimental resolved power of the present method can reach 125 MUm, which is the best resolution of terahertz digital holography to date. Furthermore, the basic detection of a biological specimen is conducted to show the practical application. In all, the results of the proposed method demonstrate the enhancement of experimental imaging resolution and that the amplitude and phase distributions of the fine structure of samples can be reconstructed by using terahertz digital holography. PMID- 26835958 TI - Optofluidic bioimaging platform for quantitative phase imaging of lab on a chip devices using digital holographic microscopy. AB - We propose a versatile 3D phase-imaging microscope platform for real-time imaging of optomicrofluidic devices based on the principle of digital holographic microscopy (DHM). Lab-on-chip microfluidic devices fabricated on transparent polydimethylsiloxane (PDMS) and glass substrates have attained wide popularity in biological sensing applications. However, monitoring, visualization, and characterization of microfluidic devices, microfluidic flows, and the biochemical kinetics happening in these devices is difficult due to the lack of proper techniques for real-time imaging and analysis. The traditional bright-field microscopic techniques fail in imaging applications, as the microfluidic channels and the fluids carrying biological samples are transparent and not visible in bright light. Phase-based microscopy techniques that can image the phase of the microfluidic channel and changes in refractive indices due to the fluids and biological samples present in the channel are ideal for imaging the fluid flow dynamics in a microfluidic channel at high resolutions. This paper demonstrates three-dimensional imaging of a microfluidic device with nanometric depth precisions and high SNR. We demonstrate imaging of microelectrodes of nanometric thickness patterned on glass substrate and the microfluidic channel. Three dimensional imaging of a transparent PDMS optomicrofluidic channel, fluid flow, and live yeast cell flow in this channel has been demonstrated using DHM. We also quantify the average velocity of fluid flow through the channel. In comparison to any conventional bright-field microscope, the 3D depth information in the images illustrated in this work carry much information about the biological system under observation. The results demonstrated in this paper prove the high potential of DHM in imaging optofluidic devices; detection of pathogens, cells, and bioanalytes on lab-on-chip devices; and in studying microfluidic dynamics in real time based on phase changes. PMID- 26835959 TI - Characterizations of transparent particle holography in near-field using Debye series. AB - The effects of the individual scattering process on the formations of both the particle hologram and its corresponding reconstructed three-dimensional particle image are investigated using the Debye series. A particle hologram model using the Debye series decomposes the object wave into different scattering modes and thus permits evaluating the effects of the individual scattering process [diffraction, reflection, transmission, refractions with (p-1) internal reflections] on the particle holography quantitatively. In the Gabor inline holography of a transparent droplet, the transmission light causes small discrepancies between the hologram fringes of an opaque particle (diffraction) and a transparent particle near the zero point of the Bessel-like modulation function, eventually giving rise to the glory spot in the center of the reconstructed dark particle image. For off-axis holography, this paper reveals the effects of reflection, particularly total reflection by bubbles, transmission, and refractions with (p-1) internal reflections of the scattered light on the formation and the reconstructed glory spot images of typical forward and backward off-axis holography. PMID- 26835960 TI - Recent progress in see-through three-dimensional displays using holographic optical elements [Invited]. AB - The principles and characteristics of see-through 3D displays are presented. We especially focus on the integral-imaging display system using a holographic optical element (IDHOE), which is able to display 3D images and satisfy the see through property at the same time. The technique has the advantage of the high transparency and capability of displaying autostereoscopic 3D images. We have analyzed optical properties of IDHOE for both recording and displaying stages. Furthermore, various studies of new applications and system improvements for IDHOE are introduced. Thanks to the characteristics of holographic volume grating, it is possible to implement a full-color lens-array holographic optical element and conjugated reconstruction as well as 2D/3D convertible IDHOE. Studies on the improvements of viewing characteristics including a viewing angle, fill factor, and resolution are also presented. Lastly, essential issues and their possible solutions are discussed as future work. PMID- 26835961 TI - Heterodyne holography with full control of both the signal and reference arms. AB - Heterodyne holography is a variant of phase-shifting holography in which the reference and signal arms are controlled by acousto-optic modulators. In this review paper, we will briefly describe the method and its properties, and we will illustrate its advantages in experimental applications. PMID- 26835962 TI - Automated tracking of temporal displacements of a red blood cell obtained by time lapse digital holographic microscopy. AB - Red blood cell (RBC) phase images that are numerically reconstructed by digital holographic microscopy (DHM) can describe the cell structure and dynamics information beneficial for a quantitative analysis of RBCs. However, RBCs investigated with time-lapse DHM undergo temporal displacements when their membranes are loosely attached to the substrate during sedimentation on a glass surface or due to the microscope drift. Therefore, we need to develop a tracking algorithm to localize the same RBC among RBC image sequences and dynamically monitor its biophysical cell parameters; this information is helpful for studies on RBC-related diseases and drug tests. Here, we propose a method, which is a combination of the mean-shift algorithm and Kalman filter, to track a single RBC and demonstrate that the optical path length of the single RBC can be continually extracted from the tracked RBC. The Kalman filter is utilized to predict the target RBC position in the next frame. Then, the mean-shift algorithm starts execution from the predicted location, and a robust kernel, which is adaptive to changes in the RBC scale, shape, and direction, is designed to improve the accuracy of the tracking. Finally, the tracked RBC is segmented and parameters such as the RBC location are extracted to update the Kalman filter and the kernel function for mean-shift tracking; the characteristics of the target RBC are dynamically observed. Experimental results show the feasibility of the proposed algorithm. PMID- 26835963 TI - Viewing angle enhancement of an integral imaging display using Bragg mismatched reconstruction of holographic optical elements. AB - Holographic-optical-element (HOE)-based integral imaging display can be applied to augmented reality. However, a narrow viewing angle is a bottleneck for commercialization. Here, we propose a method to enhance the viewing angle of the integral imaging display using Bragg mismatched reconstruction of HOEs. The viewing angle of the integral imaging display can be enlarged with two probe waves, which form two different viewing zones. The effect of Bragg mismatched reconstruction is analyzed with simulation and experiment. In order to show feasibility of the proposed method, a display experiment is demonstrated. PMID- 26835964 TI - 2016 Joint Applied Optics and Chinese Optics Letters digital holography and 3D imaging feature: introduction. AB - This digital holography and three-dimensional imaging feature issue is the second joint effort from Applied Optics (AO) and Chinese Optics Letters (COL). PMID- 26835965 TI - New thoughts on an old riddle: What determines genetic diversity within and between species? AB - The question of what determines genetic diversity has long remained unsolved by the modern evolutionary theory (MET). However, it has not deterred researchers from producing interpretations of genetic diversity by using MET. We examine the two observations of genetic diversity made in the 1960s that contributed to the development of MET. The interpretations of these observations by MET are widely known to be inadequate. We review the recent progress of an alternative framework, the maximum genetic diversity (MGD) hypothesis, that uses axioms and natural selection to explain the vast majority of genetic diversity as being at equilibrium that is largely determined by organismal complexity. The MGD hypothesis absorbs the proven virtues of MET and considers its assumptions relevant only to a much more limited scope. This new synthesis has accounted for the overlooked phenomenon of progression towards higher complexity, and more importantly, been instrumental in directing productive research. PMID- 26835966 TI - Molecular Dynamics Simulations of Small Clusters and Liquid Hydrogen Sulfide at Different Thermodynamic Conditions. AB - A new force field for the intermolecular H2S-H2S interaction has been used to study the most relevant properties of the hydrogen sulfide system from gaseous to liquid phases by means of molecular dynamics (MD) simulations. In order to check the validity of the interaction formulation, ab initio CCSD(T)/aug-cc-pVTZ calculations, including the counterpoise correction on the H2S, (H2S)2, and (H2S)3 structures optimized at the MP2/aug-cc-pVDZ level, have been performed. The (H2S)2,3 systems have been characterized by performing NVE MD simulations at decreasing values of the temperature, while the liquid sulfide behavior has been investigated considering a NpT ensemble of 512 molecules at several thermodynamic states, defined by different pressure and temperature values. Additional calculations using an ensemble of 2197 molecules at two different temperatures have been performed to investigate the liquid/vapor interface of the system. The S-S, S-H, and H-H radial distribution functions and the coordination number, calculated at the same conditions used in X-ray and neutron diffraction experiments, and the evaluated thermodynamic and structural properties have been compared successfully with experimental data, thus confirming the reliability of the force field formulation and of the MD predictions. PMID- 26835968 TI - Zwitterionic-Modified Starch-Based Stealth Micelles for Prolonging Circulation Time and Reducing Macrophage Response. AB - Over the last few decades, nanoparticles have been emerging as useful means to improve the therapeutic efficacy of drug delivery and medical diagnoses. However, the heterogeneity and complexity of blood as a medium is a fundamental problem; large amounts of protein can be adsorbed onto the surface of nanoparticles and cause their rapid clearance before reaching their target sites, resulting in the failure of drug delivery. To overcome this challenge, we present a rationally designed starch derivative (SB-ST-OC) with both a superhydrophilic moiety of zwitterionic sulfobetaine (SB) and a hydrophobic segment of octane (OC) as functional groups, which can self-assemble into "stealth" micelles (SSO micelles). The superhydrophilic SB kept the micelles stable against aggregation in complex media and imbued them with "stealth" properties, eventually extending their circulation time in blood. In stability and hemolysis tests the SSO micelles showed excellent protein resistance properties and hemocompatibility. Moreover, a phagocytosis test and cytokine secretion assay confirmed that the SSO micelles had less potential to trigger the activation of macrophages and were more suitable as a drug delivery candidate in vivo. On the basis of these results, doxorubicin (DOX), a hydrophobic drug, was used to investigate the potential application of this novel starch derivative in vivo. The results of the pharmacokinetic study showed that the values of the plasma area under the concentration curve (AUC) and elimination half-life (T1/2) of the SSO micelles were higher than those of micelles without SB modifications. In conclusion, the combination of excellent protein resistance, lower macrophage activation, and longer circulation time in vivo makes this synthesized novel starch derivative a promising candidate as a hydrophobic drug carrier for long-term circulation in vivo. PMID- 26835969 TI - Sense and Sensitivity: Physical Limits to Multicellular Sensing, Migration, and Drug Response. AB - Metastasis is a process of cell migration that can be collective and guided by chemical cues. Viewing metastasis in this way, as a physical phenomenon, allows one to draw upon insights from other studies of collective sensing and migration in cell biology. Here we review recent progress in the study of cell sensing and migration as collective phenomena, including in the context of metastatic cells. We describe simple physical models that yield the limits to the precision of cell sensing, and we review experimental evidence that cells operate near these limits. Models of collective migration are surveyed in order to understand how collective metastatic invasion can occur. We conclude by contrasting cells' sensory abilities with their sensitivity to drugs and suggesting potential alternatives to cell-death-based cancer therapies. PMID- 26835967 TI - An Anti-proteome Nanobody Library Approach Yields a Specific Immunoassay for Trypanosoma congolense Diagnosis Targeting Glycosomal Aldolase. AB - BACKGROUND: Infectious diseases pose a severe worldwide threat to human and livestock health. While early diagnosis could enable prompt preventive interventions, the majority of diseases are found in rural settings where basic laboratory facilities are scarce. Under such field conditions, point-of-care immunoassays provide an appropriate solution for rapid and reliable diagnosis. The limiting steps in the development of the assay are the identification of a suitable target antigen and the selection of appropriate high affinity capture and detection antibodies. To meet these challenges, we describe the development of a Nanobody (Nb)-based antigen detection assay generated from a Nb library directed against the soluble proteome of an infectious agent. In this study, Trypanosoma congolense was chosen as a model system. METHODOLOGY/PRINCIPAL FINDINGS: An alpaca was vaccinated with whole-parasite soluble proteome to generate a Nb library from which the most potent T. congolense specific Nb sandwich immunoassay (Nb474H-Nb474B) was selected. First, the Nb474-homologous sandwich ELISA (Nb474-ELISA) was shown to detect experimental infections with high Positive Predictive Value (98%), Sensitivity (87%) and Specificity (94%). Second, it was demonstrated under experimental conditions that the assay serves as test-of-cure after Berenil treatment. Finally, this assay allowed target antigen identification. The latter was independently purified through immuno capturing from (i) T. congolense soluble proteome, (ii) T. congolense secretome preparation and (iii) sera of T. congolense infected mice. Subsequent mass spectrometry analysis identified the target as T. congolense glycosomal aldolase. CONCLUSIONS/SIGNIFICANCE: The results show that glycosomal aldolase is a candidate biomarker for active T. congolense infections. In addition, and by proof-of-principle, the data demonstrate that the Nb strategy devised here offers a unique approach to both diagnostic development and target discovery that could be widely applied to other infectious diseases. PMID- 26835970 TI - Cost Analysis of Fluconazole Prophylaxis for Prevention of Neonatal Invasive Candidiasis. AB - BACKGROUND: Fluconazole prophylaxis (FP) in premature infants is well studied and has been shown to decrease invasive candidiasis (ICs). IC in neonates has significant financial costs; determining the cost-benefit of FP may provide additional justification for targeting high-risk neonates. We aimed to determine the IC rate in premature infants at which FP is cost-beneficial. METHODS: A decision tree cost-analysis model using cost of FP related to costs associated with IC was used. We searched PubMed for all papers that used intravenous FP and reported rates of IC in very low birth weight neonates. Average IC rates in those who received FP (2.0%; range, 0-6.1%) and in those who did not receive FP (9.2%; range, 0-20.5%) were used. Incremental hospital costs because of IC and for FP were retrieved from the literature. Sensitivity analysis was performed to determine the incremental cost of FP across the range of published IC rates. RESULTS: The average cost per patient attributed to IC in patients receiving FP was $785 versus $2617 in those not receiving FP. Sensitivity analysis demonstrates the rate of IC would need to be <2.8% for FP to lose its cost benefit. In Monte Carlo simulation, targeting infants <1000 g would lead to $50,304,333 in cost savings per year in the United States. CONCLUSIONS: FP provides a cost-advantage across most IC rates seen in the youngest premature infants. Using a rate of 2.8% for their individual high-risk neonatal intensive care unit patients, providers can determine if FP is cost-beneficial in determining for whom to provide IC prophylaxis. PMID- 26835971 TI - Vaccine Timeliness: A Cost Analysis of the Potential Implications of Delayed Pertussis Vaccination in the US. AB - BACKGROUND: Pertussis infection remains an important public health problem, particularly in infants. Despite high coverage, pertussis vaccination delays can leave infants at a vulnerable age with less protection than anticipated. METHODS: Current diphtheria-tetanus-pertussis (DTaP) vaccination timeliness for the first 3 doses in the US was estimated using National Immunization Survey data. A Markov model estimated the potential impact on outcomes and costs of a hypothetical situation of vaccination at exactly 60, 120 and 180 days, compared with current timeliness. Incidence and unit cost data came from published sources. Age specific incidence (for month of life) of pertussis and the associated probabilities of hospitalization and death for the US, during 2000-2007, were taken from a recently published US DTaP vaccination cost-effectiveness study. The cost analysis was conducted from the healthcare system's perspective over a 1 year time horizon. A regression analysis was conducted to explore the factors associated with vaccination delay. RESULTS: Current DTaP vaccination was estimated to be delayed by 16, 27 and 44 days, for the first, second and third doses, respectively, relative to vaccination at exactly 60, 120 and 180 days. The model estimated that vaccination at exactly age 60, 120 and 180 days could prevent approximately 278 pertussis cases, 103 hospitalizations and 1 death in infants aged <1 year in the US, gaining approximately 38 quality-adjusted life years and saving approximately $1.03 million in healthcare costs. CONCLUSIONS: Timely administration of infant pertussis vaccine doses could potentially reduce subsequent pertussis cases, hospitalizations, deaths and medical costs in infants aged <1 year in the US. PMID- 26835973 TI - Anaphylaxis After Immunization of Children and Adolescents in Germany. AB - BACKGROUND: Anaphylaxis is a life-threatening event. The aim of this study was to estimate the annual frequency of anaphylaxis after immunization in individuals younger than 18 years in Germany leading to hospitalization. METHODS: All suspected cases of postvaccination anaphylaxis involving individuals aged 0-17 years reported to the German surveillance unit for rare pediatric diseases (Erhebungseinheit fur seltene padiatrische Erkrankungen in Deutschland) from June 2008 through May 2010, and all suspected cases of anaphylaxis as an adverse event following immunization in the same age group reported to the Paul-Ehrlich Institut during the observational period were classified according to the Brighton collaboration case definition. Only hospitalized cases of anaphylaxis fulfilling Brighton collaboration case definition level 1-3 criteria were eligible. Estimates for the annual frequency were calculated by using capture recapture methods. RESULTS: A total of 22 reports were eligible. Median age of the affected individuals (13 males, 9 females) was 7.0 years (range: 2 months to 17 years). Anaphylaxis occurred most frequently after administration of AS03 adjuvanted A/H1N1 pandemic influenza vaccine (n = 8). The annual frequency of anaphylaxis after vaccination (excluding pandemic influenza vaccine as well as monovalent measles and rubella vaccines) was estimated to be 6.8 (95% confidence interval: 6.1-10.9). The estimated incidence of anaphylaxis after administration of specific vaccines ranged from 0.4 to 127.6 cases per 1,000,000 doses administered. CONCLUSIONS: This study confirms that anaphylaxis after immunization in children and adolescents is a rare event. AS03 adjuvanted A/H1N1 pandemic influenza vaccine seems to be associated with a higher risk of anaphylaxis when compared with other vaccines. PMID- 26835974 TI - Immunogenicity, Tolerability and Safety in Adolescents of Bivalent rLP2086, a Meningococcal Serogroup B Vaccine, Coadministered with Quadrivalent Human Papilloma Virus Vaccine. AB - BACKGROUND: This study in healthy adolescents (11 to <18 years) evaluated coadministration of quadrivalent human papillomavirus vaccine (HPV-4), with bivalent rLP2086, a meningococcal serogroup B (MnB) vaccine. METHODS: Subjects received bivalent rLP2086 + HPV-4, bivalent rLP2086 + saline or saline + HPV-4 at 0, 2 and 6 months. Immune responses to HPV-4 antigens were assessed 1 month after doses 2 and 3. Serum bactericidal assays using human complement (hSBAs) with 4 MnB test strains expressing vaccine-heterologous human complement factor H binding protein (fHBP) variants determined immune responses to bivalent rLP2086. Coprimary objectives were to demonstrate noninferior immune responses with concomitant administration compared with either vaccine alone. Additional endpoints included the proportions of subjects achieving prespecified protective hSBA titers to all 4 MnB test strains (composite response) and >=4-fold increases in hSBA titer from baseline for each test strain after dose 3; these endpoints served as the basis of licensure of bivalent rLP2086 in the US. RESULTS: The noninferiority criteria were met for all MnB test strains and HPV antigens except HPV-18; >=99% of subjects seroconverted for all 4 HPV antigens. Bivalent rLP2086 elicited a composite response in >80% of subjects and increased hSBA titers >=4 fold in >=77% of subjects for each test strain after dose 3. A substantial bactericidal response was also observed in a large proportion of subjects after dose 2. Local reactions and systemic events did not increase with concomitant administration. CONCLUSIONS: Concomitant administration of bivalent rLP2086 and HPV-4 elicits robust immune responses to both vaccines without increasing reactogenicity compared with bivalent rLP2086 alone. Concurrent administration may increase compliance with both vaccine schedules. PMID- 26835972 TI - Antiretroviral Therapy in Severely Malnourished, HIV-infected Children in Asia. AB - BACKGROUND: Information on antiretroviral therapy (ART) use in HIV-infected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population. METHODS: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index-for-age Z score less than -3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for age Z score less than -3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification. RESULTS: Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from -5.6 at ART initiation to -2.3 after 36 months. Not using trimethoprim-sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66-3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.08-2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than -4.5 vs. -3.5 to less than -3.0; 95% CI: 1.24-5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient years, and rates did not differ by malnutrition severity. CONCLUSION: Trimethoprim-sulfamethoxazole prophylaxis is important for the recovery of weight for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for age Z score, which may contribute to their high rate of mortality. PMID- 26835976 TI - Erratum. PMID- 26835975 TI - Effect of organised mammography screening on stage-specific incidence in Norway: population study. AB - BACKGROUND: We aimed to estimate the effect of organised mammography screening on breast cancer stage distribution by comparing changes in women eligible for screening, based on birth cohort, to the concurrent changes in younger, ineligible women. METHODS: In an open cohort study in Norway, which introduced national mammography screening county-by-county from 1995 to 2004, we identified women (n=49 883) diagnosed with in situ or invasive breast cancer (ICD10 codes: D05 or C50) during the period 1987-2011 and born between 1917 and 1980. We estimated relative incidence rate ratios (rIRRs) comparing the development in the screening vs historic group to the younger vs younger historic group. RESULTS: Including the compensatory drop, eligible women experienced a 68% higher increase in localised cancers (rIRR=1.68, 95% confidence interval (CI): 1.51-1.87) than younger women, while the increase in incidence of advanced cancers was similar (rIRR=1.11, 95% CI: 0.90-1.36). Excluding the prevalence round, eligible women experienced a 60% higher increase in localised cancers (rIRR=1.60, 95% CI: 1.42 1.79), while the increase in incidence of advanced cancers remained similar (rIRR=1.08, 95% CI: 0.86-1.35). CONCLUSIONS: Introduction of organised mammography screening was followed by a significant increase in localised and no change in advanced-stage cancers in women eligible for screening relative to younger, ineligible women. PMID- 26835977 TI - Benzylic Phosphates in Friedel-Crafts Reactions with Activated and Unactivated Arenes: Access to Polyarylated Alkanes. AB - Easily reachable electron-poor/rich primary and secondary benzylic phosphates are suitably used as substrates for Friedel-Crafts benzylation reactions with only 1.2 equiv activated/deactivated arenes (no additional solvent) to access structurally and electronically diverse polyarylated alkanes with excellent yields and selectivities at room temperature. Specifically, diversely substituted di/triarylmethanes are generated within 2-30 min using this approach. A wide number of electron-poor polyarylated alkanes are easily accomplished through this route by just tuning the phosphates. PMID- 26835978 TI - Asymmetric Catalysis with a Mechanically Point-Chiral Rotaxane. AB - Mechanical point-chirality in a [2]rotaxane is utilized for asymmetric catalysis. Stable enantiomers of the rotaxane result from a bulky group in the middle of the thread preventing a benzylic amide macrocycle shuttling between different sides of a prochiral center, creating point chirality in the vicinity of a secondary amine group. The resulting mechanochirogenesis delivers enantioselective organocatalysis via both enamine (up to 71:29 er) and iminium (up to 68:32 er) activation modes. PMID- 26835981 TI - Self-reported Health Care Utilization of Patients with Inflammatory Bowel Disease Correlates Perfectly with Medical Records. AB - BACKGROUND: Studies on the costs of health care in patients with inflammatory bowel disease (IBD) are increasingly conducted through the collection of self reported data. We aimed to assess the concordance between estimated annual costs based on self-reported health care utilization and administrative data in IBD. METHODS: Consecutive patients with Crohn's disease or ulcerative colitis visiting the outpatient clinic were enrolled. Participants were asked to fill out a questionnaire on their IBD-specific health care utilization over the past year. Registered health care utilization over the same time period was extracted from medical records. Health care resources were multiplied by their unit prices to obtain costs. Cost estimates were compared, and correlation, sensitivity, and specificity were calculated. RESULTS: In total, 101 patients (70 Crohn's disease, 31 ulcerative colitis) were enrolled. Mean direct health care costs were &OV0556;4758 per year according to self-reported data and &OV0556;4866 according to administrative data (r = 0.97). Hospitalizations and diagnostics were relatively underreported with a sensitivity of 75% and 88%, and a specificity of 100% and 88%, respectively. One of 7 surgical procedures was overreported, and only 1 of 25 patients did not report the use of anti-tumor necrosis factor compounds. Suffering from a flare or having a pouch predicted a decreased recall with an adjusted odds ratio of 3.5 (95% confidence interval, 1.3-9.6) and 10.7 (95% confidence interval, 1.1-107.6), respectively. CONCLUSIONS: We report a high concordance between costs of self-reported health care utilization and administrative data over the past year in IBD. Self-reported health care utilization reliably measures the consumption of health care in IBD. PMID- 26835979 TI - Irinotecan Delivery by Lipid-Coated Mesoporous Silica Nanoparticles Shows Improved Efficacy and Safety over Liposomes for Pancreatic Cancer. AB - Urgent intervention is required to improve the 5 year survival rate of pancreatic ductal adenocarcinoma (PDAC). While the four-drug regimen, FOLFIRINOX (comprising irinotecan, 5-fluorouracil, oxaliplatin, and leucovorin), has a better survival outcome than the more frequently used gemcitabine, the former treatment platform is highly toxic and restricted for use in patients with good performance status. Since irinotecan contributes significantly to FOLFIRINOX toxicity (bone marrow and gastrointestinal tract), our aim was to reduce the toxicity of this drug by a custom-designed mesoporous silica nanoparticle (MSNP) platform, which uses a proton gradient for high-dose irinotecan loading across a coated lipid bilayer (LB). The improved stability of the LB-coated MSNP (LB-MSNP) carrier allowed less drug leakage systemically with increased drug concentrations at the tumor sites of an orthotopic Kras-derived PDAC model compared to liposomes. The LB-MSNP nanocarrier was also more efficient for treating tumor metastases. Equally important, the reduced leakage and slower rate of drug release by the LB-MSNP carrier dramatically reduced the rate of bone marrow, gastrointestinal, and liver toxicity compared to the liposomal carrier. We propose that the combination of high efficacy and reduced toxicity by the LB-MSNP carrier could facilitate the use of irinotecan as a first-line therapeutic to improve PDAC survival. PMID- 26835983 TI - Experimental and Theoretical Study of CO2 Insertion into Ruthenium Hydride Complexes. AB - The ruthenium hydride [RuH(CNN)(dppb)] (1; CNN = 2-aminomethyl-6-tolylpyridine, dppb = 1,4-bis(diphenylphosphino)butane) reacts rapidly and irreversibly with CO2 under ambient conditions to yield the corresponding Ru formate complex 2. In contrast, the Ru hydride 1 reacts with acetone reversibly to generate the Ru isopropoxide, with the reaction free energy DeltaG degrees (298 K) = -3.1 kcal/mol measured by (1)H NMR in tetrahydrofuran-d8. Density functional theory (DFT), calibrated to the experimentally measured free energies of ketone insertion, was used to evaluate and compare the mechanism and energetics of insertion of acetone and CO2 into the Ru-hydride bond of 1. The calculated reaction coordinate for acetone insertion involves a stepwise outer-sphere dihydrogen transfer to acetone via hydride transfer from the metal and proton transfer from the N-H group on the CNN ligand. In contrast, the lowest energy pathway calculated for CO2 insertion proceeds by an initial Ru-H hydride transfer to CO2 followed by rotation of the resulting N-H-stabilized formate to a Ru-O bound formate. DFT calculations were used to evaluate the influence of the ancillary ligands on the thermodynamics of CO2 insertion, revealing that increasing the pi acidity of the ligand cis to the hydride ligand and increasing the sigma basicity of the ligand trans to it decreases the free energy of CO2 insertion, providing a strategy for the design of metal hydride systems capable of reversible, ergoneutral interconversion of CO2 and formate. PMID- 26835984 TI - Promoting Creativity and Innovation in a Structured Learning Environment. PMID- 26835982 TI - How Will Evolving Future Therapies and Strategies Change How We Position the Use of Biologics in Moderate to Severely Active Inflammatory Bowel Disease. AB - Several biological agents have been added to our armamentarium of treatment options for moderate to severely active inflammatory bowel diseases, and this number is expected to only increase in the near future. With our growing understanding of disease mechanisms and pharmacokinetics, we are now able to target several mechanisms of action to achieve key endpoints (steroid-free remission and mucosal healing) associated with improved long-term disease-related outcomes. In this context, concerns arise regarding the optimal positioning of currently available biologics and key biologics in development. In this review, we will discuss the currently available evidence for comparative effectiveness of biological agents approved for the use in moderate to severely active inflammatory bowel diseases, with a focus on practical considerations to be made when using these agents in practice. We will further review novel biological agents and small molecule inhibitors in development and discuss future opportunities through which providers may personalize treatment decisions to achieve optimal treatment outcomes. PMID- 26835987 TI - A pure polysaccharide from Ephedra sinica treating on arthritis and inhibiting cytokines expression. AB - In our previous study, we found that the acidic polysaccharides of Ephedra sinica had immunosuppressive effect to treat rheumatoid arthritis and the pure polysaccharide ESP-B4 was the main composition of the acidic polysaccharides. At present, the exact molecular mechanism of ESP-B4 on treating arthritis is unclear. We are thus evaluating the properties of ESP-B4 on LPS-induced THP-1 pro monocytic cells and adjuvant-induced arthritis in Wistar rats via TLR4. In vitro, ESP-B4 decreased the production of cytokines induced by LPS. In addition, ESP-B4 reduced the LPS-stimulated nuclear translocation of p65 subunit of NF-kappaB. Pretreatment with ESP-B4 significantly down-regulated the phosphorylation of MAPKs induced by LPS. Furthermore, in vivo, after 12 days of disease induced by adjuvant, rats were treated with ESP-B4 for 16 days. ESP-B4 significantly improved all parameters of inflammation. ESP-B4 reduced the release of inflammatory factors and cytokines by inhibiting the TLR4 signaling pathway to treat rheumatoid arthritis. PMID- 26835988 TI - Effects and underlying mechanisms of endotoxemia on post-incisional pain in rats. AB - AIMS: The aim of the present study was to investigate the effects and underlying mechanisms of endotoxin (lipopolysaccharide, LPS) on postoperative pain using a rat model of incisional pain. MAIN METHODS: Animals were assigned to one of four groups using a 2*2 experimental design: a single intraperitoneal injection of 5mg/kg LPS versus vehicle, by plantar incision versus anesthesia alone. Spontaneous pain and mechanical paw withdrawal threshold (PWT) were evaluated using Rat Grimace Scale (RGS) and von Frey fibers, respectively. Analgesic effects of ketoprofen, morphine, and wound infiltration with ropivacaine, as well as the contribution of the Toll-like receptor (TLR) 4 pathway, were also evaluated. In vivo single fiber recordings were performed to assess the nociceptive afferent signals from the surgical site. KEY FINDINGS: Systemic administration of LPS significantly increased the pain intensity at 2h after hind paw incision, but did not affect the PWT. The duration of post-incisional pain assessed by both scales did not significantly differ in the presence or absence of LPS. The analgesic efficiency of ketoprofen and morphine was reduced by LPS, while that of wound infiltration with ropivacaine was preserved. On the other hand, in vivo single fiber recording failed to demonstrate any significant effects of LPS on the activity of primary afferents due to mechanical stimuli. Pre-treatment with intrathecal LPS from Rhodobacter sphaeroides, a TLR-4 antagonist, almost completely inhibited LPS-induced exacerbated post-incisional pain, and decreased analgesic responsiveness. SIGNIFICANCE: The present results suggested that LPS exacerbates post-incisional pain via the central TLR-4 pathway. PMID- 26835989 TI - Therapeutic potential of endothelin inhibitors in canine hemangiosarcoma. AB - AIMS: Hemangiosarcoma (HSA) that originates from vascular endothelial cells is the most common splenic malignant neoplasm in dogs, as it accounts for approximately 20% of all canine soft tissue sarcomas. In this study, inhibitory effects of endothelin receptor antagonists on the growth of HSA cells were examined using cell lines established from canine HSA. MAIN METHODS: The preproendothelin-1 (PPET-1), endothelin type A receptor (ETA) and endothelin type B receptor (ETB) mRNA expression levels in HSA cell lines (n=5) were analyzed quantitatively by real-time RT-PCR. These levels were compared with those in HSA tissues (n=11) and those in normal splenic tissues (n=6). ETA and ETB protein expression was examined by western blot. The production and secretion of endothelin-1 (ET-1) and big ET-1 by cell lines were analyzed by measuring the levels in the culture medium by ELISA. The inhibitory effects of endothelin receptor antagonists (ambrisentan, BQ788 and bosentan) on cell growth were evaluated by WST-8 assay. KEY FINDINGS: The PPET1 and ETA mRNA expression levels were elevated in HSA tissues and HSA cell lines compared with normal tissues. In cell lines, the production of ET-1 and big ET-1 peptide as well as the expression of ETA protein were detected, but the levels of ETB were not measured. Ambrisentan and bosentan inhibited growth activity in cell lines. Ambrisentan was more effective than bosentan. SIGNIFICANCE: These findings demonstrate the importance of the ETA axis in canine HSA as well as the potential of ETA inhibitors in the treatment of canine HSA. PMID- 26835990 TI - Statistical modeling and removal of lipid membrane projections for cryo-EM structure determination of reconstituted membrane proteins. AB - This paper describes steps in the single-particle cryo-EM 3D structure determination of membrane proteins in their membrane environment. Using images of the Kv1.2 potassium-channel complex reconstituted into lipid vesicles, we describe procedures for the merging of focal-pairs of exposures and the removal of the vesicle-membrane signal from the micrographs. These steps allow 3D reconstruction to be performed from the protein particle images. We construct a 2D statistical model of the vesicle structure based on higher-order singular value decomposition (HOSVD), by taking into account the structural symmetries of the vesicles in polar coordinates. Non-roundness in the vesicle structure is handled with a non-linear shape alignment to a reference, which ensures a compact model representation. The results show that the learned model is an accurate representation of the imaged vesicle structures. Precise removal of the strong membrane signals allows better alignment and classification of images of small membrane-protein particles, and allows higher-resolution 3D reconstruction. PMID- 26835991 TI - Human C-terminally truncated ERalpha variants resulting from the use of alternative exons in the ligand-binding domain. AB - The nuclear receptor genes contain alternative internal and terminal exons, with alternative exon incorporation yielding mRNA variants that encode various receptor types, including some with C-terminal truncation that exhibit constitutive activation or dominant-negative transcriptional transactivation. However, C-terminally truncated estrogen receptor alpha (ERalpha) variants with alternative sequences have rarely been reported in humans. Therefore, we assessed human ERalpha genomic organization and alternative splicing profiles, and identified both alternative exons and C-terminally truncated ERalpha variants. These naturally occurring C-terminally truncated ERalpha proteins were localized in the nuclei of transfected cells. In addition, ERalphai45c and ERalphaDelta5 variants exhibited constitutive transactivation of an estrogen responsive element driven promoter in transfected cells. We manufactured expression vectors encoding artificially truncated ERalpha constructs and evaluated their transactivation abilities to establish mechanisms determining the constitutive activity and dominant-negative properties of truncated variants. Lack of the region encoded in exon 8 eliminated basal and ligand-induced transcriptional transactivation. The C terminally truncated ERalpha variants/constructs containing the helices 5 in their ligand-binding domains did not exhibit constitutive transactivation. Furthermore, we demonstrated that truncation from C-termini to helices 5 in the variant ligand-binding domains was required for constitutive activation and found that the remnant regions of the ligand-binding domains and variant-specific sequences influenced transcriptional transactivation efficiency. In conclusion, we elucidated the structural and functional features of novel C-terminally truncated ERalpha variants and revealed the mechanisms underlying constitutive transactivation by C-terminally truncated nuclear receptor variants. PMID- 26835992 TI - Prevention of Lower Eyelid Retraction in a Case of Inferior Rectus Muscle Recession. PMID- 26835993 TI - Large Pupils in Infancy. . .Suspected Aniridia. Multisystemic smooth muscle dysfunction syndrome secondary to an ACTA2 mutation. PMID- 26835994 TI - Getting Double Crossed. PMID- 26835995 TI - Macular Changes Following Strabismus Surgery Confirmed by the Use of Optical Coherence Tomography. PMID- 26835996 TI - Macular Thickness Following Strabismus Surgery as Determined by Optical Coherence Tomography. AB - PURPOSE: To investigate macular changes following strabismus surgery by using optical coherence tomography (OCT). METHODS: The authors prospectively evaluated 60 eyes of 30 patients undergoing unilateral extraocular muscle surgery. OCT measurements employing the fast macular thickness mapping protocol were performed 1 day prior to surgery and 1 day postoperatively. Postoperative macular changes in the study eye that was operated on (n = 30) were compared with the fellow control eye (n = 30, controls). RESULTS: There was an increase in mean +/- standard deviation central foveal thickness (CFT) in the operated eyes, from 201.63 +/- 18.36 um at baseline to 206.03 +/- 22.73 um postoperatively (P = .024). Preoperative and postoperative perifoveal outer temporal quadrant thicknesses were 220.10 +/- 16.23 and 225.80 +/- 14.78 um, respectively (P = .009). There were no differences between preoperative and postoperative retinal thickness measurements for all measured areas in the control eyes. Eyes that underwent surgery involving the rectus muscles showed a trend toward a greater CFT increase compared with eyes that had oblique muscle surgery (P = .070). CONCLUSIONS: The authors found subclinical increases in the foveal and perifoveal macular thicknesses following extraocular muscle surgery. These findings could be attributed to change in the mechanical forces caused by the new position of the extraocular muscles and transmitted via the sclera or, alternatively, to postoperative inflammation and alterations in the blood-retinal barrier. The clinical implications of these findings remain to be clarified. PMID- 26835997 TI - Clinical Evaluation of Four-Muscle Tenotomy Surgery for Nystagmus. AB - PURPOSE: To document prospectively the effect of four-muscle tenotomy surgery on visual acuity (VA) and nystagmus intensity and assess, by the use of a questionnaire, the experience of adult patients and the parents of children who have had the four-muscle tenotomy procedure for nystagmus in the absence of strabismus or an anomalous head position. The qualitative perceived benefits or lack thereof from the procedure were compared to the subjective effects on nystagmus intensity and VA. METHODS: Fifteen patients diagnosed as having congenital/infantile or acquired nystagmus, including albinism or other visual sensory disorders without anomalous head positions or coexisting strabismus, were included in this study. The changes in preoperative and postoperative VA and nystagmus were evaluated based on clinical and perceptual measurements and video recordings. RESULTS: All 15 patients had preoperative and postoperative ophthalmological examinations. One patient had a postoperative conjunctival cyst, which was successfully removed. Fourteen patients (93%) showed clinical VA improvement in at least one eye. Fourteen patients were video recorded preoperatively and postoperatively to analyze their nystagmus intensity; case 9 was not included. Postoperatively, 10 patients (71%) showed a decrease in nystagmus intensity. Thirteen patients (87%) perceived vision improvement and 11 patients (73%) perceived a decrease in nystagmus intensity. All patients experienced either clinically improved VA or a decrease in nystagmus intensity. Fourteen patients (93%) perceived either improved VA or a decrease in nystagmus intensity. The preoperative and postoperative changes in VA (P = .002) and nystagmus intensity (P = .043) were both statistically significant. CONCLUSIONS: The authors have shown that four-muscle tenotomy surgery for nystagmus can improve VA and decrease nystagmus intensity. The study yielded subjective patient satisfaction, modest objective improvement in VA, and no significant complications. PMID- 26835998 TI - Episodic Excessive Blinking in Children. AB - PURPOSE: Many children present with excessive blinking. Categorization, associated conditions, and prognosis are controversial. METHODS: All children with excessive blinking were reviewed, excluding those with known uveitis, glaucoma, or obvious eyelid abnormalities. Parents were telephoned for follow-up. RESULTS: No ocular pathology was identified in 31 of 34 children with excessive blinking (91%). Parents were able to report a specific cause of blinking in 7 (21%). In 24 of 34 (71%), parents reported complete resolution of excessive blinking. No new ophthalmologic diagnoses were uncovered on follow-up. CONCLUSIONS: Episodes of excessive blinking rarely indicate neurologic disorders and frequently resolve spontaneously. PMID- 26835999 TI - Pediatric Ophthalmologists' Experiences With Abusive Head Trauma. AB - PURPOSE: To estimate the number of cases of abusive head trauma seen by pediatric ophthalmologists and analyze factors associated with physician subpoenas and court testimonies. METHODS: Pediatric ophthalmologists were surveyed about their experiences with abusive head trauma. The survey was sent to 875 active members of the American Association for Pediatric Ophthalmology and Strabismus (AAPOS). RESULTS: The response rate was 15% (132 surveys). The median pediatric ophthalmologist is consulted 10.0 (interquartile range [IQR] = 4.0 to 19.0) times per year to evaluate patients for abusive head trauma and sees 2.5 (IQR = 1.0 to 6.0) patients with probable abusive head trauma each year. Pediatric ophthalmologists were equally likely to be subpoenaed (4.6% vs 4.8%, P = .84) or to testify (1.9% vs 1.7%, P = .79) whether they did or did not perform retinal photography. Physicians were equally likely to be subpoenaed (4.8% vs 7.1%, P = .92) or to testify (2.2% vs 0.0%, P = .17) whether a child abuse team was involved in patient care or not. Geographic location had no statistical significance on how frequently pediatric ophthalmologists were subpoenaed (P = .17) or testified in court (P = .12). When a pediatric ophthalmologist was subpoenaed to court, the median number of missed clinic days was 1.0 (IQR = 1.0 to 2.0), with an estimated cost of $3,000 (IQR = $1,750 to $4,750) in lost revenue. CONCLUSIONS: Obtaining retinal imaging, having a child abuse team, and geographic location had no significant relationship with how often pediatric ophthalmologists were subpoenaed or testified in court. PMID- 26836000 TI - Ophthalmic Manifestations in Children With Congenital Hypothyroidism. AB - PURPOSE: To evaluate the frequencies of ophthalmic abnormalities in children with congenital hypothyroidism. METHODS: A total of 121 patients with a history of congenital hypothyroidism, aged 1 to 216 months, were included in the study. The initial ophthalmological examinations and demographic data of patients who were examined between April 2013 and April 2015 were retrospectively reviewed. Accompanying systemic abnormalities were also noted. RESULTS: Ophthalmic pathology was determined in 40.4% (49 of 121) of patients with congenital hypothyroidism, of which 79.5% (39 of 49) had significant refractive errors and 32.6% (16 of 49) had strabismus. Systemic abnormalities were observed in 74.3% (90 of 121) of the children, among which 47.1% (57 of 121) were congenital heart defects and 38.0% (46 of 121) were neurologic abnormalities. A high prevalence of Down syndrome (17.3%; 21 of 121) and atopic dermatitis (8.2%; 10 of 121) was detected among patients with congenital hypothyroidism. CONCLUSIONS: In addition to many associated systemic abnormalities, ophthalmic pathologies may also occur in children with congenital hypothyroidism. Thus, routine ophthalmological examination is recommended for these children, starting from the time of initial diagnosis. PMID- 26836001 TI - Spontaneous Regression of Over-elevation in Adduction Following Esotropia Surgery. AB - PURPOSE: To evaluate the course of over-elevation in adduction in patients who had esotropia following correction of horizontal deviation. METHODS: The review of the medical files identified 28 patients who had esotropia with over-elevation in adduction. Data collected from the patients' full ophthalmological examinations included visual acuity, ocular alignment, duction, versions and sensory tests for binocularity and stereopsis, cycloplegic retinoscopy, and fundus evaluation. Oblique muscle function was graded on a scale of -4 to +4. The primary outcome measure was the amount of improvement in over-elevation in adduction following esotropia surgery. RESULTS: Of the 28 patients (mean age: 53.5 +/- 53.7 months), 13 were males and 15 were females. Of these, 22 (78.6%) had infantile esotropia and 6 (21.4%) had partial accommodative esotropia. The mean follow-up was 16.3 +/- 7.9 months. All patients underwent bilateral medial rectus recession for correction of esotropia. The mean preoperative inferior oblique overaction was +2.1 +/- 0.7 and the final postoperative value was +0.8 +/ 0.9 (P < .001). There was a statistically significant decrease in postoperative over-elevation in adduction at all postoperative visits compared to the preoperative value (P < .001 at 3- and 6-month and final visits). Over-elevation in adduction regressed in 42 eyes (80.8%). Of these, 18 eyes (34.6%) completely resolved without any additional surgery to the inferior oblique muscle. CONCLUSIONS: Spontaneous regression in over-elevation in adduction was observed after esotropia surgery without additional inferior oblique weakening surgery. This may affect presurgical evaluation of and surgical planning for patients. PMID- 26836002 TI - Unaugmented Muscle Union Surgery for Heavy Eye Syndrome Without Combined Medial Rectus Recession. AB - PURPOSE: Simple loop myopexy or retro-equitorial muscle union surgery has been shown to effectively treat the strabismus seen in heavy eye syndrome. In most cases, this has been described with combined recession of the medial rectus muscle, particularly where medial rectus contracture was demonstrated on forced duction testing intraoperatively. The authors report the outcomes of muscle union surgery alone without combined medial rectus recession in 29 eyes with heavy eye syndrome. METHODS: A retrospective review was conducted of 26 patients and 29 eyes with heavy eye syndrome treated with a simple loop myopexy procedure. The preoperative and postoperative deviations in primary position were measured along with restriction in ocular motility in abduction and elevation. Patients with residual esotropia and/or persistence of symptoms were offered a second-stage medial rectus recession procedure. RESULTS: In 21 patients, muscle union was sufficient in improving the diplopia or cosmetic appearance of the eyes. In these cases, the average preoperative deviation improved from 21.2 +/- 16.3 to 5.5 +/- 9.1 prism diopters (PD). Eight eyes went on to have a second-stage medial rectus recession with excellent outcomes. CONCLUSIONS: The authors found that muscle union surgery alone is an effective and successful procedure in restoring the ocular motility disturbance and also in treating heavy eye syndrome. There was a much lower incidence (up to 70% lower) of medial rectus recession than other similar case series. There were no cases of overcorrection and no complications. PMID- 26836003 TI - Clinical Preoperative and Postoperative Symptoms of Exotropia. AB - PURPOSE: To examine clinical preoperative and postoperative symptoms and changes in exotropia according to constancy and age. METHODS: A survey was conducted of 50 patients on the day before and 1 month after exotropia surgery. Survey results were analyzed by type of exotropia at presentation and age. Changes in subjective symptoms from preoperatively to postoperatively were examined for stereopsis (5 items), asthenopia (5 items), and appearance (5 items). Each item was rated on a 5-point scale ranging from 0 to 4. RESULTS: The mean age of the 50 patients was 10.6 +/- 7.75 years, and there were 21 (41.2%) males and 29 (56.9%) females. Thirty-two patients with intermittent exotropia had no significant improvement in the stereopsis or asthenopia symptoms. However, they showed significant (P < .05) improvement in the appearance symptoms of squint and out of focus. Eighteen patients with constant exotropia showed significant improvements in the symptoms of tripping over objects or running into a wall in stereopsis and of squint and out of focus in appearance (P < .05). Postoperatively, all patients had significant improvement in appearance-related symptoms regardless of age (P < .05). CONCLUSIONS: Patients with constant exotropia had improved symptoms in stereopsis, asthenopia, and appearance after surgery. Appearance was improved regardless of the type of exotropia or age. PMID- 26836004 TI - A Multi-tool to Reduce Nasolacrimal Stent Complications With the Home-Removable Farson Crawford Tube. AB - PURPOSE: Tear duct obstruction can be treated with probing and stenting, providing a reduced reoperation rate. A new instrument combining punctual dilation with the graduated diameter probe and bony-rasp was developed to assist the procedure. METHODS: Laterality, type of nasolacrimal disorder, type of procedure, patient age, and postoperative outcome were monitored for one surgeon for two decades. RESULTS: From 617 cases of pediatric tear duct obstruction, 494 used the bilateral, monocanalicular Farson method, yielding a 1.7% reoperation rate and 0.6% wire-strip rate. The nasolacrimal duct dilator rasp multi-tool, used since 1996, had a similarly low rate of complications. CONCLUSIONS: The Farson technique with the multi-tool provides an affordable, effective procedure for childhood nasolacrimal obstruction, allowing home removal of the stent. PMID- 26836006 TI - A Novel Preoperative Planning Approach for Strabismus Surgery. PMID- 26836005 TI - Assessment of Grating Acuity in Infants and Toddlers Using an Electronic Acuity Card: The Dobson Card. AB - PURPOSE: To determine if testing binocular visual acuity in infants and toddlers using the Acuity Card Procedure (ACP) with electronic grating stimuli yields clinically useful data. METHODS: Participants were infants and toddlers ages 5 to 36.7 months referred by pediatricians due to failed automated vision screening. The ACP was used to test binocular grating acuity. Stimuli were presented on the Dobson Card. The Dobson Card consists of a handheld matte-black plexiglass frame with two flush-mounted tablet computers and is similar in size and form to commercially available printed grating acuity testing stimuli (Teller Acuity Cards II [TACII]; Stereo Optical, Inc., Chicago, IL). On each trial, one tablet displayed a square-wave grating and the other displayed a luminance-matched uniform gray patch. Stimuli were roughly equivalent to the stimuli available in the printed TACII stimuli. After acuity testing, each child received a cycloplegic eye examination. Based on cycloplegic retinoscopy, patients were categorized as having high or low refractive error per American Association for Pediatric Ophthalmology and Strabismus vision screening referral criteria. Mean acuities for high and low refractive error groups were compared using analysis of covariance, controlling for age. RESULTS: Mean visual acuity was significantly poorer in children with high refractive error than in those with low refractive error (P = .015). CONCLUSIONS: Electronic stimuli presented using the ACP can yield clinically useful measurements of grating acuity in infants and toddlers. Further research is needed to determine the optimal conditions and procedures for obtaining accurate and clinically useful automated measurements of visual acuity in infants and toddlers. PMID- 26836007 TI - 2015 Reviewers. PMID- 26836008 TI - Ectopic Eyelid Cilia. PMID- 26836010 TI - In vivo electric conductivity of cervical cancer patients based on B1+ maps at 3T MRI. AB - The in vivo electric conductivity (sigma) values of tissue are essential for accurate electromagnetic simulations and specific absorption rate (SAR) assessment for applications such as thermal dose computations in hyperthermia. Currently used sigma-values are mostly based on ex vivo measurements. In this study the conductivity of human muscle, bladder content and cervical tumors is acquired non-invasively in vivo using MRI. The conductivity of 20 cervical cancer patients was measured with the MR-based electric properties tomography method on a standard 3T MRI system. The average in vivo sigma-value of muscle is 14% higher than currently used in human simulation models. The sigma-value of bladder content is an order of magnitude higher than the value for bladder wall tissue that is used for the complete bladder in many models. Our findings are confirmed by various in vivo animal studies from the literature. In cervical tumors, the observed average conductivity was 13% higher than the literature value reported for cervical tissue. Considerable deviations were found for the electrical conductivity observed in this study and the commonly used values for SAR assessment, emphasizing the importance of acquiring in vivo conductivity for more accurate SAR assessment in various applications. PMID- 26836009 TI - Effects of Acyclovir, Foscarnet, and Ribonucleotides on Herpes Simplex Virus-1 DNA Polymerase: Mechanistic Insights and a Novel Mechanism for Preventing Stable Incorporation of Ribonucleotides into DNA. AB - We examined the impact of two clinically approved anti-herpes drugs, acyclovir and Forscarnet (phosphonoformate), on the exonuclease activity of the herpes simplex virus-1 DNA polymerase, UL30. Acyclovir triphosphate and Foscarnet, along with the closely related phosphonoacetic acid, did not affect exonuclease activity on single-stranded DNA. Furthermore, blocking the polymerase active site due to either binding of Foscarnet or phosphonoacetic acid to the E-DNA complex or polymerization of acyclovir onto the DNA also had a minimal effect on exonuclease activity. The inability of the exonuclease to excise acyclovir from the primer 3'-terminus results from the altered sugar structure directly impeding phosphodiester bond hydrolysis as opposed to inhibiting binding, unwinding of the DNA by the exonuclease, or transfer of the DNA from the polymerase to the exonuclease. Removing the 3'-hydroxyl or the 2'-carbon from the nucleotide at the 3'-terminus of the primer strongly inhibited exonuclease activity, although addition of a 2'-hydroxyl did not affect exonuclease activity. The biological consequences of these results are twofold. First, the ability of acyclovir and Foscarnet to block dNTP polymerization without impacting exonuclease activity raises the possibility that their effects on herpes replication may involve both direct inhibition of dNTP polymerization and exonuclease-mediated destruction of herpes DNA. Second, the ability of the exonuclease to rapidly remove a ribonucleotide at the primer 3'-terminus in combination with the polymerase not efficiently adding dNTPs onto this primer provides a novel mechanism by which the herpes replication machinery can prevent incorporation of ribonucleotides into newly synthesized DNA. PMID- 26836011 TI - Patients with Mild Alzheimer's Disease Fail When Using Their Working Memory: Evidence from the Eye Tracking Technique. AB - Patients with Alzheimer's disease (AD) develop progressive language, visuoperceptual, attentional, and oculomotor changes that can have an impact on their reading comprehension. However, few studies have examined reading behavior in AD, and none have examined the contribution of predictive cueing in reading performance. For this purpose we analyzed the eye movement behavior of 35 healthy readers (Controls) and 35 patients with probable AD during reading of regular and high-predictable sentences. The cloze predictability of words N - 1, and N + 1 exerted an influence on the reader's gaze duration. The predictabilities of preceding words in high-predictable sentences served as task-appropriate cues that were used by Control readers. In contrast, these effects were not present in AD patients. In Controls, changes in predictability significantly affected fixation duration along the sentence; noteworthy, these changes did not affect fixation durations in AD patients. Hence, only in healthy readers did predictability of upcoming words influence fixation durations via memory retrieval. Our results suggest that Controls used stored information of familiar texts for enhancing their reading performance and imply that contextual-word predictability, whose processing is proposed to require memory retrieval, only affected reading behavior in healthy subjects. In AD patients, this loss reveals impairments in brain areas such as those corresponding to working memory and memory retrieval. These findings might be relevant for expanding the options for the early detection and monitoring in the early stages of AD. Furthermore, evaluation of eye movements during reading could provide a new tool for measuring drug impact on patients' behavior. PMID- 26836012 TI - Brain Metabolism Correlates of the Free and Cued Selective Reminding Test in Mild Cognitive Impairment. AB - Free and Cued Selective Reminding Test (FCSRT) measures immediate and delayed episodic memory and cueing sensitivity and is suitable to detect prodromal Alzheimer's disease (AD). The present study aimed at investigating the segregation effect of FCSRT scores on brain metabolism of memory-related structures, usually affected by AD pathology, in the Mild Cognitive Impairment (MCI) stage. A cohort of forty-eight MCI patients underwent FCSRT and 18F-FDG PET. Multiple regression analysis showed that Immediate Free Recall correlated with brain metabolism in the bilateral anterior cingulate and delayed free recall with the left anterior cingulate and medial frontal gyrus, whereas semantic cueing sensitivity with the left posterior cingulate. FCSRT in MCI is associated with neuro-functional activity of specific regions of memory-related structures connected to hippocampal formation, such as the cingulate cortex, usually damaged in AD. PMID- 26836013 TI - Aberrant Spontaneous Brain Activity in Patients with Mild Cognitive Impairment and concomitant Lacunar Infarction: A Resting-State Functional MRI Study. AB - BACKGROUND: Lacunar infarctions (LI) have been associated with a cognitive decline and an increased risk of dementia. Whether and how the pattern of spontaneous brain activity in patients with mild cognitive impairment (MCI) differs in subjects with and without concomitant LI remains unclear. OBJECTIVE: To compare the pattern of spontaneous brain activity in MCI patients with versus those without LI using resting-state functional magnetic resonance imaging (rs fMRI). METHODS: Forty-eight MCI patients, including 22 with LI [MCI-LI] and 26 without LI [MCI-no LI], and 28 cognitive normal subjects underwent rs-fMRI post processed using regional homogeneity (ReHo) and the amplitude of low-frequency fluctuation (ALFF) methods. RESULTS: Compared with cognitively normal subjects, the MCI-LI patients had decreased ReHo in the precuneus/cuneus (Pcu/CU) and insula; decreased ALFF in the Pcu/CU and frontal lobe; and increased ALFF and ReHo in the temporal lobe. While the MCI-no LI group had increased ReHo and ALFF in the bilateral hippocampus and parahippocampal gyrus, frontal lobe, and decreased ALFF and ReHo in the temporal lobe. Compared with the MCI-no LI patients, those with MCI-LI had decreased ALFF in the frontal lobe; decreased ReHo in the Pcu/CU and insula; and increased ALFF and ReHo in the temporal lobe (p < 0.05, AlphaSim corrected). In MCI-LI patients, the MOCA scores showed a relatively weak correlation with ALFF values in the medial frontal gyrus (r = 0.432, p = 0.045) (of borderline significance after Bonferroni correction). CONCLUSIONS: The spontaneous brain activities in MCI-LI were distinct from MCI-no LI. The probable compensatory mechanism observed in MCI-no LI might be disrupted in MCI with LI due to vascular damage. PMID- 26836014 TI - Morroniside-Induced PP2A Activation Antagonizes Tau Hyperphosphorylation in a Cellular Model of Neurodegeneration. AB - BACKGROUND: An accumulation of hyperphosphorylated tau in the brain is a hallmark of Alzheimer's disease (AD). Deficits in protein phosphatase 2A (PP2A) are associated with tau hyperphosphorylation in AD. OBJECTIVE: To investigate the effects of morroniside (MOR), isolated from Cornus officinalis, on tau hyperphosphorylation and its underlying mechanisms related to PP2A. METHODS: SK-N SH cells were pretreated with 50-200 MUM MOR for 24 h followed by 20 nM okadaic acid (OA) for 6 h. PP2Ac siRNA was transfected into HEK293 cells to determine the direct interaction of MOR with PP2A. Western blotting was used to measure the expression of proteins and enzymes. PP2A activity was measured by molybdenum blue spectrophotometry. RESULTS: Pretreatment with MOR improved the cellular morphological damage and inhibited tau hyperphosphorylation in SK-N-SH cells induced by OA, a PP2A inhibitor. Moreover, MOR increased PP2A activity, concurrent with a decrease in the expression of demethylated PP2A at Leu309 and phosphorylated PP2A at Tyr307. MOR decreased protein phosphatase methylesterase 1 (PME-1) expression and the ratio of PME-1/leucine carboxyl methyltransferase 1 (LCMT-1). Furthermore, MOR treatment decreased the phosphorylation of Src at Tyr416, which regulates the phosphorylation of PP2A. MOR had no effect on PP2Ac expression and tau hyperphosphorylation in PP2Ac siRNA-transfected cells. CONCLUSION: MOR attenuated OA-induced tau hyperphosphorylation via PP2A activation, and its mechanism might be related to the regulation of PP2Ac post translational modification and upstream enzymes such as Src and PME-1. PMID- 26836016 TI - Diagnostic Assessment and Management of Dysphagia in Patients with Alzheimer's Disease. AB - A growing concern in patients affected by Alzheimer's disease (AD) is dysphagia, or swallowing impairment, which leads to malnutrition, dehydration, weight loss, functional decline and fear of eating and drinking, as well as a decrease in the quality of life. Thus the diagnostic assessment of dysphagia in patients with AD is imperative to ensure that they receive effective management, avoiding complications, and reducing comorbidity and mortality in such a growing population. Dysphagia management requires a multidisciplinary approach considering that no single strategy is appropriate for all patients. However, evidence for clinical diagnostic assessment, interventions, and medical management of dysphagia in these patients are still limited: few studies are reporting the evaluation and the management among this group of patients. Here we analyzed the most recent findings in diagnostic assessment and management of swallowing impairment in patients affected by AD. PMID- 26836015 TI - Cholesterol, 24-Hydroxycholesterol, and 27-Hydroxycholesterol as Surrogate Biomarkers in Cerebrospinal Fluid in Mild Cognitive Impairment and Alzheimer's Disease: A Meta-Analysis. AB - Abnormal cholesterol metabolism is an established feature of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) is the fluid surrounding the central nervous system, and the protein and lipid content alterations in the CSF could be biomarkers for degenerative changes in the brain. The laboratory diagnosis of AD is limited to the analysis of three biomarkers in CSF: Abeta42, total tau, and phospho-tau. The purpose of this analysis is to systematically analyze the available data describing the biomarkers of cholesterol and its metabolites in the CSF of subjects with AD. MEDLINE, EMBASE, and the Cochrane Central database were systematically queried to collect studies that have evaluated the markers of cholesterol and its metabolites in the CSF of subjects with mild cognitive impairment (MCI) or AD and age-matched controls. Analysis of the published data shows that the levels of cholesterol are increased in MCI subjects; 24 hydroxycholesterol and 27-hydroxycholesterol are elevated in AD and MCI subjects compared to controls. There is a significant dysfunction of cholesterol metabolism in the CSF of AD subjects. This analysis indicates that in addition to the available biomarkers in the CSF, such as Abeta42, total tau, and phospho-tau, 24-hydroxycholesterol, 27-hydroxycholesterol, and cholesterol appear to be sensitive biomarkers for the evaluation of MCI and AD. PMID- 26836017 TI - Secondary Structures in a Freeze-Dried Lignite Humic Acid Fraction Caused by Hydrogen-Bonding of Acidic Protons with Aromatic Rings. AB - A lignite humic acid (HA) was separated from inorganic and non-HA impurities (i.e., aluminosilicates, metals) and fractionated by a combination of dialysis and XAD-8 resin. Fractionation revealed a more homogeneous structure of lignite HA. New and more specific structural information on the main lignite HA fraction is obtained by solid-state nuclear magnetic resonance (NMR) spectroscopy. Quantitative (13)C multiple cross-polarization (multiCP) NMR indicated oxidized phenyl propane structures derived from lignin. MultiCP experiments, conducted on potassium HA salts titrated to pH 10 and pH 12, revealed shifts consistent with carboxylate and phenolate formation, but structural changes associated with enolate formation from aromatic beta keto acids were not detected. Two dimensional (1)H-(13)C heteronuclear correlation (2D HETCOR) NMR indicated aryl aliphatic ketones, aliphatic and aromatic carboxyl groups, phenol, and methoxy phenyl ethers. Acidic protons from carboxyl groups in both the lignite HA fraction and a synthetic HA-like polycondensate were found to be hydrogen-bonded with electron-rich aromatic rings. Our results coupled with published infrared spectra provide evidence for the preferential hydrogen bonding of acidic hydrogens with electron-rich aromatic rings rather than adjacent carbonyl groups. These hydrogen-bonding interactions likely result from stereochemical arrangements in primary structures and folding. PMID- 26836018 TI - Mechanical Control of Individual Superconducting Vortices. AB - Manipulating individual vortices in a deterministic way is challenging; ideally, manipulation should be effective, local, and tunable in strength and location. Here, we show that vortices respond to local mechanical stress applied in the vicinity of the vortex. We utilized this interaction to move individual vortices in thin superconducting films via local mechanical contact without magnetic field or current. We used a scanning superconducting quantum interference device to image vortices and to apply local vertical stress with the tip of our sensor. Vortices were attracted to the contact point, relocated, and were stable at their new location. We show that vortices move only after contact and that more effective manipulation is achieved with stronger force and longer contact time. Mechanical manipulation of vortices provides a local view of the interaction between strain and nanomagnetic objects as well as controllable, effective, and reproducible manipulation technique. PMID- 26836019 TI - Distribution and genetic characterization of Enterovirus G and Sapelovirus A in six Spanish swine herds. AB - The prevalence of Enterovirus G (EV-G) and Sapelovirus A (PSV-1) was investigated in Spanish swine herds by means of cross-sectional studies. Faecal samples from clinically healthy pigs were collected from six farms, and analysed by RT-PCR. The results indicated a high prevalence of EV-G detected in nearly all the animals older than 3 weeks of age. Otherwise, PSV-1 was only detected in 3-week old piglets from one of the farms. Genetic analyses performed in the VP1 region of the EV-G indicated circulation of diverse strains in the same farm, related to genotypes G1, G2, G3, G4, G6, G9, G12, G13 and G14. Moreover, co-infection of several PSV-1 variants in the same animal was evident, typical of viral quasispecies. Evolutionary pressure analysis indicated that microevolution of PSV 1 seems to be driven by negative selection. This study gives further insights in the epidemiology of EV-G and PSV-1. PMID- 26836022 TI - Editorial Compilation I. PMID- 26836020 TI - Biochemical, biophysical, and functional properties of ICA512/IA-2 RESP18 homology domain. AB - BACKGROUND: ICA512 (or IA-2/PTPRN) is a transmembrane protein-tyrosine phosphatase located in secretory granules of neuroendocrine cells. Previous studies implied its involvement in generation, cargo storage, traffic, exocytosis and recycling of insulin secretory granules, as well as in beta-cell proliferation. While several ICA512 domains have been characterized, the function and structure of a large portion of its N-terminal extracellular (or lumenal) region are unknown. Here, we report a biophysical, biochemical, and functional characterization of ICA512-RESP18HD, a domain comprising residues 35 to 131 and homologous to regulated endocrine-specific protein 18 (RESP18). METHODS: Pure recombinant ICA512-RESP18HD was characterized by CD and fluorescence. Its binding to insulin and proinsulin was characterized by ELISA, surface plasmon resonance, and fluorescence anisotropy. Thiol reactivity was measured kinetically. Targeting of DeltaRESP18HD ICA512-GFP to the membrane of insulinoma cells was monitored by immunofluorescence. RESULTS: ICA512-RESP18HD possesses a strong tendency to aggregate and polymerize via intermolecular disulfide formation, particularly at pH>4.5. Its cysteine residues are highly susceptible to oxidation forming an intramolecular disulfide between cysteine 53 and 62 and intermolecular disulfides via cysteine 40 and cysteine 47. The regulated sorting of ICA512 to secretory granules in INS-1 cells was impaired by deletion of RESP18HD. ICA512-RESP18HD binds with high-affinity to insulin and proinsulin. CONCLUSIONS: RESP18HD is required for efficient sorting of ICA512 to secretory granules. GENERAL SIGNIFICANCE: RESP18HD is a key determinant for ICA512 granule targeting. PMID- 26836023 TI - In vitro degradation and mechanical properties of PLA-PCL copolymer unit cell scaffolds generated by two-photon polymerization. AB - The manufacture of 3D scaffolds with specific controlled porous architecture, defined microstructure and an adjustable degradation profile was achieved using two-photon polymerization (TPP) with a size of 2 * 4 * 2 mm(3). Scaffolds made from poly(D,L-lactide-co-E-caprolactone) copolymer with varying lactic acid (LA) and E -caprolactone (CL) ratios (LC16:4, 18:2 and 9:1) were generated via ring-opening-polymerization and photoactivation. The reactivity was quantified using photo-DSC, yielding a double bond conversion ranging from 70% to 90%. The pore sizes for all LC scaffolds were see 300 MUm and throat sizes varied from 152 to 177 MUm. In vitro degradation was conducted at different temperatures; 37, 50 and 65 degrees C. Change in compressive properties immersed at 37 degrees C over time was also measured. Variations in thermal, degradation and mechanical properties of the LC scaffolds were related to the LA/CL ratio. Scaffold LC16:4 showed significantly lower glass transition temperature (T g) (4.8 degrees C) in comparison with the LC 18:2 and 9:1 (see 32 degrees C). Rates of mass loss for the LC16:4 scaffolds at all temperatures were significantly lower than that for LC18:2 and 9:1. The degradation activation energies for scaffold materials ranged from 82.7 to 94.9 kJ mol(-1). A prediction for degradation time was applied through a correlation between long-term degradation studies at 37 degrees C and short-term studies at elevated temperatures (50 and 65 degrees C) using the half life of mass loss (Time (M1/2)) parameter. However, the initial compressive moduli for LC18:2 and 9:1 scaffolds were 7 to 14 times higher than LC16:4 (see 0.27) which was suggested to be due to its higher CL content (20%). All scaffolds showed a gradual loss in their compressive strength and modulus over time as a result of progressive mass loss over time. The manufacturing process utilized and the scaffolds produced have potential for use in tissue engineering and regenerative medicine applications. PMID- 26836024 TI - Synthesis of Phosphorus-Centered and Chalcogen-Bridged Concave Molecules: Modulation of Bowl Geometries and Packing Structures by Changing Bridging Atoms. AB - A series of phosphorus-centered concave molecules having oxygen and sulfur as bridging atoms, C3v-symmetric P4 and Cs-symmetric P2 and P3, were newly synthesized. The packing diagrams of the concave molecules P1-P4 are dependent on the bridging atoms, columnar structures for P1 and P4, and zigzag structures for P2 and P3. The bowl depth becomes shallower in the order of P1, P2, P3, and P4 as the number of bridging sulfur atoms increases. PMID- 26836025 TI - A collection of non-human primate computed tomography scans housed in MorphoSource, a repository for 3D data. AB - A dataset of high-resolution microCT scans of primate skulls (crania and mandibles) and certain postcranial elements was collected to address questions about primate skull morphology. The sample consists of 489 scans taken from 431 specimens, representing 59 species of most Primate families. These data have transformative reuse potential as such datasets are necessary for conducting high power research into primate evolution, but require significant time and funding to collect. Similar datasets were previously only available to select research groups across the world. The physical specimens are vouchered at Harvard's Museum of Comparative Zoology. The data collection took place at the Center for Nanoscale Systems at Harvard. The dataset is archived on MorphoSource.org. Though this is the largest high fidelity comparative dataset yet available, its provisioning on a web archive that allows unlimited researcher contributions promises a future with vastly increased digital collections available at researchers' finger tips. PMID- 26836026 TI - Results of a course based obesity intervention program during work. AB - BACKGROUND: Overweight and obesity are becoming more and more relevant for armed forces in westernized countries, especially with respect to the impact on recruitment and soldiers' performance. The German Armed Forces have been organizing a Military Obesity Intervention Program (OIP) in Warendorf, Germany, since 2001. In addition to the existing outpatient program, a course version was offered. This course version is of interest since it offers a potential alternative to outpatient programs. OBJECTIVE: To analyse the results obtained from the course version of the OIP and comparing these to other OIPs. METHODS: Retrospective analysis of the course version of the OIP, starting in 2001, based on an intention-to-treat analysis. RESULTS: 334 participants showed significant improvement (p < 0.05) in bodyweight (-3.4+/-6.6 kg), body mass index (-1.0+/ 2.0 kg/m2), waist circumference (-3.8+/-6.4 cm), systolic and diastolic blood pressure (-5.6+/-18.0/-3.3+/-12.8 mm Hg), physical capacity (+11.4+/-32.6 Watt), total cholesterol (-0.16+/-0.94 mmol/l), HDL (+0.04+/-0.23 mmol/l), LDL ( 0.16+/-0.80 mmol/l), uric acid (-31.2+/-69.3 MUmol/l) and hemoglobin A1c ( 0.13+/-0.52%). The entire OIP course was completed by 180 participants (53.9%). 27.5% of all 334 participants had reduced their body weight by 5% or more during their participation in the OIP. CONCLUSIONS: In this specific OIP only a small number of obese patients reduced their bodyweight, even though the examined parameters improved significantly. Therefore, greater efforts need to be undertaken in order to prevent overweight and obesity in the military in addition to the implemented obesity intervention programs. PMID- 26836027 TI - The call for cognitive ramps. PMID- 26836028 TI - Survey of polycyclic aromatic hydrocarbons of vegetable oils and oilseeds by GC MS in China. AB - There is a lack of information regarding the occurrence and content of contamination of polycyclic aromatic hydrocarbon (PAH) in edible vegetable oils and oilseeds used for oil production in China. By combining the advantages of ultrasound-assisted extraction, low temperature separation and silica SPE purification, a method for the determination of the USEPA, 16 PAHs was developed based on GC-MS to fill this gap. The method recoveries for oils and oilseeds were 84.4-113.8% and 84.3-115.3%, respectively. The LODs and LOQs for 16 PAHs were ranged from 0.06-0.17 and 0.19-0.56 MUg kg(-1), respectively. Based on the established method, PAH concentrations in 21 edible oils and 17 oilseeds were determined. Almost all the PAHs were found in all the samples tested, especially the light PAHs (LPAHs). Three oil samples exceeded the maximum level of 10 MUg kg(-1) for BaP set by China. However, five and six oil samples, respectively, exceeded the maximum limits of 2 and 10 MUg kg(-1) set for BaP and PAH4 by the European Union. The concentrations of PAH16 in oilseed samples were 1.5 times higher than corresponding oil samples. The relationships between PAH4 and PAH8, PAH4 and PAH16 as well as PAH8 and PAH16 indicates that PAH4 is a sufficient surrogate for the contamination level of PAHs in edible oils when compared with PAH8. PMID- 26836029 TI - In Vitro and In Vivo Immunomodulatory Activity of Okra (Abelmoschus esculentus L.) Polysaccharides. AB - Crude okra (Abelmoschus esculentus L.) polysaccharide (RPS) was obtained by water extraction and alcohol precipitation. Three purified fractions of RPS, designated RPS-1, RPS-2, and RPS-3, were fractioned by diethylaminoethyl (DEAE)-cellulose chromatography. Their molecular weights, monosaccharide compositions, infrared (Fourier transform infrared [FT-IR]) spectra, and nuclear magnetic resonance (NMR) spectra were analyzed. Their immunomodulatory activity was evaluated with an in vitro cell model (RAW264.7 cells). In vivo immunomodulatory activity of RPS 2 was evaluated in normal and cyclophosphamide-induced immunosuppressed mice. The results showed that the molecular weights of RPS-1, RPS-2, and RPS-3 were 600, 990, and 1300 kDa, respectively. RPS-1 and RPS-2 were mainly composed of galactose, rhamnose, galacturonic acid, and glucuronic acid, while RPS-3 was mainly composed of galactose, rhamnose, galacturonic acid, glucuronic acid, and glucose. FT-IR and NMR spectrum data indicated a rhamnogalacturonan I characteristic of polysaccharide. Both RPS and its purified fractions RPS-1, RPS 2, and RPS-3 significantly increased RAW264.7 cell proliferation, nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression, and tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-10 secretion (P < .05). The purified fraction RPS-2 also increased the spleen index, splenocyte proliferation, and cytokine secretion in vivo. These results indicate that okra polysaccharides may potentially serve as novel immunomodulators. PMID- 26836030 TI - Treatment patterns, symptom reduction, quality of life, and resource use associated with lubiprostone in irritable bowel syndrome constipation subtype. AB - Objectives Real-world patient outcomes data is scarce concerning the high disease burden of IBS-C. The aim of this study was to compare patient-reported symptom control, health-related quality of life (HRQoL), resource utilization, and treatment satisfaction of lubiprostone vs non-lubiprostone treatment for irritable bowel syndrome-constipation (IBS-C). Research design and methods An observational, retrospective US chart review and computer-assisted telephone patient survey was conducted March to August 2013 recruiting women over 18 years old with physician-confirmed IBS-C who had initiated new treatment from inadequate relief of previous treatments and who had been on the new treatment >=3 months. Multiple IBS-C treatments were permitted. IBS-C severity, time since diagnosis, age, and race were controlled using inverse probability of treatment weighting. Weighted outcomes were compared using t-tests (continuous outcomes) and chi-squared tests (categorical outcomes). Main outcomes measures Instruments included Patient Assessment of Constipation Symptoms (PAC-SYM) and IBS quality of life (IBS-QoL). A single item assessed current treatment satisfaction. Results Of 162 patients (mean age 45.9 [SD 15.3] years old, 71% white, 61.1% with moderate IBS-C), 76 switched to lubiprostone and 86 to non-lubiprostone. Groups were similar in clinical and demographic characteristics and previous 30 day IBS-C treatment. After weighting, all PAC-SYM scores were lower for lubiprostone (P < 0.05). All IBS-QoL subscales were higher for lubiprostone including overall, dysphoria, social reaction, sexual, and relationship scores (P < 0.05.) More lubiprostone patients reported positive treatment satisfaction (92.3% vs 71.0%, P < 0.001). Conclusions In IBS-C patients with inadequate response to previous therapies, lubiprostone improved patient-reported symptom control, treatment satisfaction, and HRQoL. Key limitations include lack of measurement of patient reported outcomes at treatment start and potential data gaps in chart documentation. PMID- 26836031 TI - Mutations acquired during cell culture isolation may affect antigenic characterisation of influenza A(H3N2) clade 3C.2a viruses. AB - As elsewhere, few (< 15%) sentinel influenza A(H3N2) clade 3C.2a viruses that dominated in Canada during the 2014/15 season could be antigenically characterised by haemagglutination inhibition (HI) assay. Clade 3C.2a viruses that could be HI-characterised had acquired genetic mutations during in vitro cell culture isolation that modified the potential glycosylation motif found in original patient specimens and the consensus sequence of circulating viruses at amino acid positions 158-160 of the haemagglutinin protein. Caution is warranted in extrapolating antigenic relatedness based on limited HI findings for clade 3C.2a viruses that continue to circulate globally. PMID- 26836032 TI - Empiric treatment of nosocomial spontaneous bacterial peritonitis: One size does not fit all. PMID- 26836033 TI - Big Animal Cloning Using Transgenic Induced Pluripotent Stem Cells: A Case Study of Goat Transgenic Induced Pluripotent Stem Cells. AB - Using of embryonic stem cells (ESCs) could improve production traits and disease resistance by improving the efficiency of somatic cell nuclear transfer (SCNT) technology. However, robust ESCs have not been established from domestic ungulates. In the present study, we generated goat induced pluripotent stem cells (giPSCs) and transgenic cloned dairy goat induced pluripotent stem cells (tgiPSCs) from dairy goat fibroblasts (gFs) and transgenic cloned dairy goat fibroblasts (tgFs), respectively, using lentiviruses that contained hOCT4, hSOX2, hMYC, and hKLF4 without chemical compounds. The giPSCs and tgiPSCs expressed endogenous pluripotent markers, including OCT4, SOX2, MYC, KLF4, and NANOG. Moreover, they were able to maintain a normal karyotype and differentiate into derivatives from all three germ layers in vitro and in vivo. Using SCNT, tgFs and tgiPSCs were used as donor cells to produce embryos, which were named tgF-Embryos and tgiPSC-Embryos. The fusion rates and cleavage rates had no significant differences between tgF-Embryos and tgiPSC-Embryos. However, the expression of IGF-2, which is an important gene associated with embryonic development, was significantly lower in tgiPSC-Embryos than in tgF-Embryos and was not significantly different from vivo-Embryos. PMID- 26836034 TI - Surgical Resident Duty-Hour Rules--Weighing the New Evidence. PMID- 26836037 TI - Catalytic Promiscuity of Transaminases: Preparation of Enantioenriched beta Fluoroamines by Formal Tandem Hydrodefluorination/Deamination. AB - Transaminases are valuable enzymes for industrial biocatalysis and enable the preparation of optically pure amines. For these transformations they require either an amine donor (amination of ketones) or an amine acceptor (deamination of racemic amines). Herein transaminases are shown to react with aromatic beta fluoroamines, thus leading to simultaneous enantioselective dehalogenation and deamination to form the corresponding acetophenone derivatives in the absence of an amine acceptor. A series of racemic beta-fluoroamines was resolved in a kinetic resolution by tandem hydrodefluorination/deamination, thus giving the corresponding amines with up to greater than 99 % ee. This protocol is the first example of exploiting the catalytic promiscuity of transaminases as a tool for novel transformations. PMID- 26836038 TI - Kinetically Controlling Surface Structure to Construct Defect-Rich Intermetallic Nanocrystals: Effective and Stable Catalysts. AB - Kinetic control of surface defects is achieved, and cubic, concave cubic, and defect-rich cubic intermetallic Pt3 Sn nanocrystals are prepared for the electro oxidation of formic acid. The generality of this kinetic approach is demonstrated by the fabrication of Pt-Mn nanocrystals with different surface defects. The defect-rich nanocrystals exhibit high catalytic activity and stability concurrently, indicating their potential application in fuel cells. PMID- 26836036 TI - Indications, reconstructive techniques, and results for total glossectomy. AB - BACKGROUND: The best treatment for advanced tongue tumors remains controversial. Total glossectomy with laryngeal preservation is considered a feasible option, despite its morbidity. METHODS: A retrospective analysis of 12 total glossectomies with laryngeal preservation was performed in order to assess the available reconstruction techniques and analyze survival and functional outcomes. RESULTS: One-year overall survival (OS) and disease-free survival (DFS) rates were 58.3% and 33.3%, respectively, both dropping to 25% after 3 years. Permanent gastrostomy was necessary in 10 patients, although videofluoroscopy revealed adequate tolerance to liquids. Speech intelligibility was satisfactory in 50% of the patients and severely impaired in the remaining 50%. CONCLUSION: Laryngeal preservation in the context of advanced tumors of the tongue without supraglottic invasion carried similar oncologic results to total glossectomy with laryngectomy, but offers a better phonatory function. However, it is usually associated with a higher gastrostomy dependency ratio. A scrupulous selection of candidates is mandatory. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2004 E2010, 2016. PMID- 26836035 TI - Experiences and Lessons Learned in Using Community-Based Participatory Research to Recruit Asian American Immigrant Research Participants. AB - PURPOSE: By 2050, the number of international migrants is expected to double from 214 million people. Of these, Asian immigrants are projected to comprise the largest foreign-born population in the United States by the year 2065. Asian American immigrants experience numerous health disparities, but remain under represented in health research. The purpose of this article is to examine the experiences and lessons learned in applying community-based participatory research (CBPR) principles to access and recruit a sample of Asian American research participants. APPROACH: This article reviews unique barriers to research participation among Asian Americans, describes the principles of CBPR, and provides examples of how these principles were employed to bridge recruitment challenges within a qualitative study. FINDINGS AND CONCLUSIONS: CBPR facilitated greater research participation among a group of immigrant Asian Americans. Researchers must be additionally mindful of the importance of building trusting relationships with their community partners, understanding the significance of shared experiences, considering fears around immigration status, and considering ongoing challenges in identifying and reaching hidden populations. CLINICAL RELEVANCE: Clinicians and researchers can employ CBPR principles to guide their work with Asian immigrant communities and other under-represented groups to facilitate access to the population, improve participant recruitment, and foster engagement and collaboration. PMID- 26836039 TI - [Ge=Ge](4-) Dumbbells in the Zintl Phase Li3NaGe2. AB - Ge-Ge double bonds: The reaction of elemental lithium, sodium, and germanium at 750 degrees C results in the Zintl phase Li3NaGe2 , which, according to the Zintl-Klemm concept, contains [Ge=Ge](4-) dumbbells with unprecedented short Ge Ge distances. Based on structural, spectroscopic, and theoretical considerations, convincing evidence is given that Ge-Ge double bonds are in fact present. PMID- 26836040 TI - Torsional stress in DNA limits collaboration among reverse gyrase molecules. AB - Reverse gyrase is an enzyme that can overwind (introduce positive supercoils into) DNA using the energy obtained from ATP hydrolysis. The enzyme is found in hyperthermophiles, and the overwinding reaction generally requires a temperature above 70 degrees C. In a previous study using microscopy, we have shown that 30 consecutive mismatched base pairs (a bubble) in DNA serve as a well-defined substrate site for reverse gyrase, warranting the processive overwinding activity down to 50 degrees C. Here, we inquire how multiple reverse gyrase molecules may collaborate with each other in overwinding one DNA molecule. We introduced one, two, or four bubbles in a linear DNA that tethered a magnetic bead to a coverslip surface. At 40-71 degrees C in the presence of reverse gyrase, the bead rotated clockwise as viewed from above, to relax the DNA twisted by reverse gyrase. Dependence on the enzyme concentration indicated that each bubble binds reverse gyrase tightly (dissociation constant < 0.1 nm) and that bound enzyme continuously overwinds DNA for > 5 min. Rotation with two bubbles was significantly faster compared with one bubble, indicating that overwinding actions are basically additive, but four bubbles did not show further acceleration except at 40 degrees C where the activity was very low. The apparent saturation is due to the hydrodynamic friction against the rotating bead, as confirmed by increasing the medium viscosity. When torsional stress in the DNA, determined by the friction, approaches ~ 7 pN.nm (at 71 degrees C), the overwinding activity of reverse gyrase drops sharply. Multiple molecules of reverse gyrase collaborate additively within this limit. PMID- 26836041 TI - Validation of immunocytochemistry as a morphomolecular technique. AB - Immunocytochemistry (ICC) is a long-established means for clinical laboratories to investigate material for which it is difficult to obtain tissue samples. Unlike immunohistochemistry (IHC), the cells do not retain surrounding tissue environment/architecture. This can be of benefit in that fixation is often immediate and rapid, protecting the cells. Although fixation is frequently observed as the main preanalytic variable of test quality, all cytology preanalytic factors should be identified and controlled. In addition, the validation of ICC should take the same rigorous approach that other molecular pathology techniques follow. A three-step validation protocol is offered here. The end result is a comprehensive, morphomolecular approach to ICC, with an emphasis on therapeutic ICC. Cancer Cytopathol 2016;124:540-5. (c) 2016 American Cancer Society. PMID- 26836043 TI - Influence of probiotics, included in peanut butter, on the fate of selected Salmonella and Listeria strains under simulated gastrointestinal conditions. AB - AIMS: This study observed the behaviour of probiotics and selected bacterial pathogens co-inoculated into peanut butter during gastrointestinal simulation. METHODS AND RESULTS: Peanut butter homogenates co-inoculated with Salmonella/Listeria strains (5 log CFU ml(-1) ) and lyophilized or cultured probiotics (9 log CFU ml(-1) ) were exposed to simulated gastrointestinal conditions for 24 h at 37 degrees C. Sample pH, titratable acidity and pathogen populations were determined. Agar diffusion assay was performed to assess the inhibitory effect of probiotic culture supernatants with either natural (3.80 (Lactobacillus), 3.78 (Bifidobacteirum) and 5.17 (Streptococcus/Lactococcus)) or neutralized (6.0) pH. Antibacterial effect of crude bacteriocin extracts were also evaluated against the pathogens. After 24 h, samples with probiotics had lower pH and higher titratable acidity than those without probiotics. The presence of probiotics caused a significant reduction (P < 0.05) in pathogen populations. Supernatants of Bifidobacterium and Lactobacillus cultures inhibited pathogen growth; however, the elevation of pH diminished their antibacterial activities. Crude bacteriocin extracts had a strain-specific inhibitory effect only towards Listeria monocytogenes. CONCLUSION: Probiotics in 'peanut butter' survived simulated gastrointestinal conditions and inhibited the growth of Salmonella/Listeria. SIGNIFICANCE AND IMPACT OF THE STUDY: Peanut butter is a plausible carrier to deliver probiotics to improve the gastrointestinal health of children in developing countries. PMID- 26836042 TI - Metabolism of hyperpolarized [1-(13)C]pyruvate through alternate pathways in rat liver. AB - The source of hyperpolarized (HP) [(13)C]bicarbonate in the liver during metabolism of HP [1-(13)C]pyruvate is uncertain and likely changes with physiology. Multiple processes including decarboxylation through pyruvate dehydrogenase or pyruvate carboxylase followed by subsequent decarboxylation via phosphoenolpyruvate carboxykinase (gluconeogenesis) could play a role. Here we tested which metabolic fate of pyruvate contributed to the appearance of HP [(13)C]bicarbonate during metabolism of HP [1-(13)C]pyruvate by the liver in rats after 21 h of fasting compared to rats with free access to food. The (13)C NMR of HP [(13)C]bicarbonate was observed in the liver of fed rats, but not in fasted rats where pyruvate carboxylation and gluconeogenesis was active. To further explore the relative fluxes through pyruvate carboxylase versus pyruvate dehydrogenase in the liver under typical conditions of hyperpolarization studies, separate parallel experiments were performed with rats given non-hyperpolarized [2,3-(13)C]pyruvate. (13)C NMR analysis of glutamate isolated from the liver of rats revealed that flux from injected pyruvate through pyruvate dehydrogenase was dominant under fed conditions whereas flux through pyruvate carboxylase dominated under fasted conditions. The NMR signal of HP [(13)C]bicarbonate does not parallel pyruvate carboxylase activity followed by subsequent decarboxylation reaction leading to glucose production. In the liver of healthy well-fed rats, the appearance of HP [(13)C]bicarbonate exclusively reflects decarboxylation of HP [1-(13)C]pyruvate via pyruvate dehydrogenase. PMID- 26836044 TI - Serum and Vitreous Pentraxin 3 Concentrations in Patients with Diabetic Retinopathy. AB - OBJECTIVE: Pentraxin 3 (PTX3), an acute-phase glycoprotein, is correlated with inflammation. Inflammation is mechanistically involved in the development of diabetic retinopathy (DR). This study was performed to investigate the association of serum and vitreous PTX3 concentrations with the occurrence of DR. METHODS: This study enrolled 52 type 2 diabetes mellitus (T2DM) patients (20 without DR and 32 patients with proliferative diabetic retinopathy [PDR]). Serum and vitreous PTX3 concentrations were examined by using an enzyme-linked immunosorbent assay. RESULTS: PDR patients showed significantly increased concentrations of serum and vitreous PTX3 concentrations compared with the control group and T2DM patients without DR. Higher serum and vitreous PTX3 concentrations were detected in T2DM patients without DR than those in the controls. CONCLUSION: Serum and vitreous PTX3 concentrations are associated with the occurrence of DR. PMID- 26836047 TI - beta4 integrin in hereditary and acquired mucocutaneous diseases. PMID- 26836048 TI - Dissociation mediates the association between intimate partner violence and posttraumatic stress among treatment-seeking incarcerated women. AB - OBJECTIVE: Women in prison experience high rates of interpersonal trauma as well as elevated rates of posttraumatic stress disorder (PTSD) relative to women in the general population. The present study examined the relationship between recent intimate partner violence (IPV), additional forms of lifetime trauma exposure, trait dissociation, and posttraumatic stress among a sample of incarcerated female survivors of IPV. METHOD: Participants were 186 treatment seeking incarcerated women who reported experiences of IPV in the year prior to incarceration. Participants completed self-report measures of IPV, nonpartner perpetrated lifetime trauma exposure, trait dissociation, and PTSD symptomatology. Associations among study variables were evaluated using sequential multiple regression. RESULTS: Participants reported experiencing several forms of interpersonal trauma. More than half of respondents (i.e., 53%) fell beyond a conservative cutoff score on the PTSD Checklist-Civilian Version, indicating clinically significant symptoms of PTSD. Trait dissociation partially mediated the association between IPV and PTSD symptoms above and beyond history of nonpartner-perpetrated violence. Trait dissociation emerged as the strongest independent predictor of PTSD symptoms and explained approximately 15% of the variance in PTSD symptoms. CONCLUSION: This finding highlights the need for additional research concerning dissociation among women in prison and warrants consideration in future research and intervention efforts focused on trauma recovery among incarcerated women. PMID- 26836049 TI - Prostate Cancer: PI-RADS Version 2 Helps Preoperatively Predict Clinically Significant Cancers. AB - Purpose To retrospectively analyze whether Prostate Imaging Reporting and Data System (PI-RADS) version 2 is helpful for the detection of clinically significant prostate cancer. Materials and Methods Institutional review board approved this retrospective study. A total of 425 patients with prostate cancer who had undergone magnetic resonance (MR) imaging and radical prostatectomy were included. Preoperative parameters such as prostate-specific antigen, biopsy Gleason score, greatest percentage of the core, percentage of the positive core number, and score at PI-RADS version 2 with MR imaging were investigated. Two independent readers performed PI-RADS scoring. Clinically significant prostate cancer was defined as follows: (a) Gleason score of 7 or greater, (b) tumor volume of 0.5 cm(3) or greater, or a (c) positive extracapsular extension or seminal vesicle invasion. The reference standard was based on review of surgical specimen. Logistic regression was conducted to determine which parameters are associated with the presence of clinically significant cancer. Interreader agreement (ie, score >=4 or not) was investigated by using kappa statistics. Results At univariate analysis, all of the preoperative parameters were significant for clinically significant prostate cancer (P < .05). However, multivariate analysis revealed that PI-RADS score was the only significant parameter for both readers (reader 1: odds ratio = 28.170, P = .002; reader 2: odds ratio = 5.474, P = .007). The interreader agreement was excellent for PI RADS score of 4 or greater (weighted kappa = 0.801; 95% confidence interval: 0.737, 0.865). Conclusion The use of PI-RADS version 2 may help preoperatively diagnose clinically significant prostate cancer. ((c)) RSNA, 2016. PMID- 26836050 TI - Is There an Association between STARD Statement Adherence and Citation Rate? AB - Purpose To determine if adherence to the Standards for Reporting of Diagnostic Accuracy (STARD) is associated with postpublication citation rates. Materials and Methods A comprehensive search of PubMed, EMBASE, and Cochrane Library databases was performed to identify published articles that have evaluated adherence of diagnostic accuracy studies to the STARD statement. These were included if the number of STARD items reported ("STARD result") could be obtained for each evaluated study. The date of publication, journal impact factor, and citation rate (citations per day) were extracted for the diagnostic accuracy studies. Univariate correlations were performed to identify any association between STARD result, impact factor, and citation rate. Multivariate regression analysis was performed to explore the effect of impact factor on postpublication citation rates. Results The authors were able to obtain the STARD results for 1002 "original" diagnostic accuracy studies from eight different "STARD evaluation" articles. The median impact factor was 3.97 (interquartile range [IQR]: 2.32 6.21), the median STARD result was 15 of 25 items (IQR: 12-18), and the median citation rate was 0.007 citations per day (IQR: 0.0032-0.017). The authors identified a weak positive correlation between STARD result and citation rate (r = 0.096; 95% confidence interval [CI]: 0.034, 0.157), a moderate positive correlation between impact factor and citation rate (r = 0.58; 95% CI: 0.535, 0.617), and a weak positive correlation between impact factor and STARD result (r = 0.13; 95% CI: 0.064, 0.186). Multivariate analysis accounting for journal clustering effects revealed that, when impact factor is partialed out, the positive correlation between citation rate and STARD result does not persist (r = 0.029; 95% CI: -0.033, 0.091). Conclusion There is a positive correlation between completeness of reporting, as evaluated with STARD, and citation rate as well as impact factor. When adjusted for impact factor, the positive correlation between completeness of reporting and citation rate does not persist. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26836051 TI - Added sensitivity of component-resolved diagnosis in hymenoptera venom-allergic patients with elevated serum tryptase and/or mastocytosis. AB - BACKGROUND: Anaphylaxis caused by hymenoptera venom allergy is associated with elevation of baseline serum tryptase (sBT) and/or mastocytosis in about 5% of patients. Up to now, no information has become available on single venom allergen sIgE reactivity and the usefulness of component-resolved approaches to diagnose this high-risk patient group. To address the component-resolved sIgE sensitization pattern and diagnostic sensitivity in hymenoptera venom-allergic patients with elevated sBT levels and/or mastocytosis, a panel of yellow jacket and honeybee venom allergens was applied on a widely used IgE immunoassay platform. METHODS: Fifty-three patients with mastocytosis and/or elevated sBT tryptase level and systemic reactions to hymenoptera venoms were analyzed for their IgE reactivity to recombinant yellow jacket and honeybee venom allergens by Immulite3 g. RESULTS: sIgE reactivity to Ves v 1, Ves v 5, Api m 1 to Api m 4 and Api m 10 was found at a similar frequency in hymenoptera venom-allergic patients with and without elevated sBT levels and/or mastocytosis. However, the use of the recombinant allergens and a diagnostic cutoff of 0.1 kUA /L allowed the diagnosis of patients with otherwise undetectable IgE to venom extract. The diagnostic sensitivity of yellow jacket venom allergy using the combination of Ves v 1 and Ves v 5 was 100%. CONCLUSIONS: In high-risk patients with elevated sBT levels and/or mastocytosis, the use of molecular components and decreasing the threshold sIgE level to 0.1 kUA /L may be needed to avoid otherwise undetectable IgE to hymenoptera venom extracts in about 8% of such patients. PMID- 26836053 TI - Is Staphylococcal Screening and Suppression an Effective Interventional Strategy for Reduction of Surgical Site Infection? AB - BACKGROUND: Staphylococcus aureus has been recognized as a major microbial pathogen for over 100 y, having the capacity to produce a variety of suppurative and toxigenic disease processes. Many of these infections are life-threatening, with particularly enhanced virulence in hospitalized patients with selective risk factors. Strains of methicillin-resistant Staphylococcus aureus (MRSA) have rapidly spread throughout the healthcare environment such that approximately 20% of S. aureus isolates recovered from surgical site infections are methicillin resistant, (although this is now reducing following national screening and suppression programs and high impact interventions). METHODS: Widespread nasal screening to identify MRSA colonization in surgical patients prior to admission are controversial, but selective, evidence-based studies have documented a reduction of surgical site infection (SSI) after screening and suppression. RESULTS: Culture methods used to identify MRSA colonization involve selective, differential, or chromogenic media. These methods are the least expensive, but turnaround time is 24-48 h. Although real-time polymerase chain reaction (RT-PCR) technology provides rapid turnaround (1-2 h) with exceptional testing accuracy, the costs can range from three to 10 times more than conventional culture methodology. Topical mupirocin, with or without pre-operative chlorhexidine showers or skin wipes, is the current "gold-standard" for nasal decolonization, but inappropriate use of mupirocin is associated with increasing staphylococcal resistance. CONCLUSIONS: Selection of an effective active universal or targeted surveillance strategy should be based upon the relative risk of MSSA or MRSA surgical site infection in patients undergoing orthopedic or cardiothoracic device related surgical procedures. PMID- 26836052 TI - Student HPV vaccine attitudes and vaccine completion by education level. AB - PURPOSE: We describe HPV vaccine attitudes among students of different education levels. METHODS: High school, college, and graduate-level health care professional students were surveyed regarding HPV vaccine knowledge, attitudes, and receipt. Relationships between categorical variables were analyzed using chi square tests of independence and z-tests for proportions. Means for quantitative variables were compared using t-tests and one-way analysis of variance. RESULTS: 57% and 42% of the 889 students reported starting and completing HPV vaccine series, respectively, with no statistical difference by education level. 61% of students who reported receiving a provider recommendation had completed the series, compared to 6% of those who did not receive recommendation (p<0.001). The belief that HPV vaccine prevents cancer was strongly associated with vaccine completion (p=0.003). CONCLUSION: HPV vaccine coverage rates remain suboptimal. Future interventions should focus on improving provider recommendation and patient belief that HPV vaccine prevents cancer. PMID- 26836054 TI - A prospective review of appetite loss and recovery time in primary joint replacement patients. AB - INTRODUCTION: Appetite loss is commonly reported by patients following major surgery, including total joint arthroplasty (TJA). A number of studies have examined related problems, particularly in relation to physiological responses to surgery. However, no published paper has looked specifically at the duration of appetite loss in total knee arthroplasty (TKA) and total hip arthroplasty (THA) patients. METHODS: A simple, established appetite screening tool was administered preoperatively and at 2-week intervals postoperatively in 50 TJA patients until appetite levels returned to preoperative levels. The results were examined for various descriptive parameters and compared using the chi-squared test. RESULTS: Thirty-three patients underwent TKA and 17 THA. There were 27 female and 23 male patients. No patients were lost to follow-up. The median time for return of appetite in both male and female patients was 4 weeks (interquartile range [IQR]: male, 2-4; female, 4-6). The median time for return of appetite was 4 weeks both in TKA patients (IQR 4-6) and in those undergoing THA (IQR 4-4). The time to return of appetite was not significantly associated with either the gender of the patients (p=0.13) or the type of joint replacement (p=0.49). CONCLUSIONS: The study provides a clear time frame for return of appetite in uncomplicated primary joint replacements. This is a commonly noted patient problem that has not previously been specifically reviewed. PMID- 26836055 TI - Clostridium difficile-associated diarrhoea in primary joint arthroplasty in Aneurin Bevan University Health Board South. AB - INTRODUCTION: The choice of perioperative antibiotics to reduce the prevalence of infection after joint arthroplasty should be considered carefully to minimise the risk of nosocomial infections. Dramatic increases in the incidence and severity of healthcare-associated Clostridium difficile infection with Clostridium difficile-associated diarrhoea (CDAD) have occurred since 2000. METHODS: A retrospective audit of patients who underwent total hip and total knee replacement between 1 January 2005 and 31 December 2007 was undertaken in Aneurin Bevan University Health Board South (ABHBS). Stool samples from patients who had diarrhoea <12 months of surgery were recorded. Positive samples for CDAD <1 month of surgery were identified. After the change in practice in June 2010, a re-audit linked joint-replacement patients between 1 July 2010 and 26 June 2013 with infection control-records for CDAD-positive cases. RESULTS: In the first audit cycle, 1900 joint procedures were carried out in 1845 patients. There were 4 cases of CDAD <1 month of surgery (0.22%). In the re-audit period, 2591 joint procedures were undertaken in 2400 patients: no cases of CDAD <1 month of surgery were recorded. Fisher's exact test gave a two-tailed p=0.036. CONCLUSIONS: The significant reduction in CDAD cases after the change in perioperative antibiotic regimen for primary joint arthroplasty mirrored a 66% reduction in overall CDAD cases in the ABUHBS between 2008 and 2012. This reduction was accompanied by financial savings in antibiotics and nursing hours. PMID- 26836056 TI - Income and heart disease: Neglected risk factor. AB - OBJECTIVE: To determine the unadjusted and adjusted effects of income on heart disease; its main disease intermediary, high blood pressure; and its main behavioural risk factors, smoking and physical inactivity. DESIGN: Random-digit dialing telephone survey collected through the Canadian Community Health Survey by Statistics Canada. SETTING: Saskatchewan. PARTICIPANTS: A total of 27 090 residents aged 20 years and older; each health region in Saskatchewan was represented. MAIN OUTCOME MEASURES: Overall, 178 variables related to demographic characteristics, socioeconomic factors, behaviour, life stress, disease intermediaries, health outcomes, and access to health care were analyzed to determine their unadjusted and adjusted effects on heart disease. RESULTS: The mean age of the sample was 52.6 years. Women represented 55.9% of the sample. Most respondents were married (52.3%) and had some postsecondary or graduate education (52.5%). The mean personal income was $23 931 and the mean household income was $37 533. All models statistically controlled for age. Five covariates independently associated with heart disease included high blood pressure, household income of $29 999 or less per year, being a daily smoker, male sex, and being physically inactive. Five covariates independently associated with high blood pressure included being overweight or obese, being a daily smoker, household income of $29 999 or less per year, male sex, and being physically inactive. Five covariates independently associated with daily smoking included being a visible minority, household income of $29 999 or less per year, not being overweight or obese, education level of less than secondary school, and male sex. Six covariates independently associated with physical inactivity included being a visible minority, being overweight or obese, education level of less than secondary school, male sex, household income of $29 999 or less per year, and being a daily smoker. CONCLUSION: Household income was strongly and independently associated with heart disease; its main disease intermediary, high blood pressure; and its main behavioural risk factors, smoking and physical inactivity. Income inequality is a neglected risk factor worthy of appropriate public debate and policy intervention. PMID- 26836057 TI - Novel technique to treat melasma in Chinese: The combination of 2940-nm fractional Er:YAG and 1064-nm Q-switched Nd:YAG laser. AB - Melasma is one of the most common pigmented lesions in Chinese women. Although topical therapies are the mainstay treatment, lasers are being used increasingly to treat pigmented lesions. Laser treatment of melasma is however still controversial. This is because lasers have not been able to produce complete clearance of melasma and recurrence rates are high. Laser treatments also cause complications such as hypopigmentation and post-inflammatory hyperpigmentation. In this article, we report on a novel technique using a combination of fractional 2940-nm Er:YAG and 1064-nm Q-switched Nd:YAG lasers. We achieved a rapid improvement in two cases of melasma in Chinese type III skin. The improvement was seen rapidly within a month of treatment. Follow-up at 6 months showed sustained results with no complications. This novel technique is able to safely confer excellent and sustained clearance within a short treatment time. PMID- 26836058 TI - The SPOT effect: People spontaneously prefer their own theories. AB - People often exhibit confirmation bias: They process information bearing on the truth of their theories in a way that facilitates their continuing to regard those theories as true. Here, we tested whether confirmation bias would emerge even under the most minimal of conditions. Specifically, we tested whether drawing a nominal link between the self and a theory would suffice to bias people towards regarding that theory as true. If, all else equal, people regard the self as good (i.e., engage in self-enhancement), and good theories are true (in accord with their intended function), then people should regard their own theories as true; otherwise put, they should manifest a spontaneous preference for their own theories (i.e., a SPOT effect). In three experiments, participants were introduced to a theory about which of two imaginary alien species preyed upon the other. Participants then considered in turn several items of evidence bearing on the theory and each time evaluated the likelihood that the theory was true versus false. As hypothesized, participants regarded the theory as more likely to be true when it was arbitrarily ascribed to them as opposed to an "Alex" (Experiment 1) or to no one (Experiment 2). We also found that the SPOT effect failed to converge with four different indices of self-enhancement (Experiment 3), suggesting that it may be distinctive in character. PMID- 26836059 TI - Recent progress in stem cell differentiation directed by material and mechanical cues. AB - Stem cells play essential roles in tissue regeneration in vivo via specific lineage differentiation induced by environmental factors. In the past, biochemical signals were the focus of induced stem cell differentiation. As reported by Engler et al (2006 Cell 126 677-89), biophysical signal mediated stem cell differentiation could also serve as an important inducer. With the advancement of material science, it becomes a possible strategy to generate active biophysical signals for directing stem cell fate through specially designed material microstructures. In the past five years, significant progress has been made in this field, and these designed biophysical signals include material elasticity/rigidity, micropatterned structure, extracellular matrix (ECM) coated materials, material transmitted extracellular mechanical force etc. A large number of investigations involved material directed differentiation of mesenchymal stem cells, neural stem/progenitor cells, adipose derived stem cells, hematopoietic stem/progenitor cells, embryonic stem cells and other cells. Hydrogel based materials were commonly used to create varied mechanical properties via modifying the ratio of different components, crosslinking levels, matrix concentration and conjugation with other components. Among them, polyacrylamide (PAM) and polydimethylsiloxane (PDMS) hydrogels remained the major types of material. Specially designed micropatterning was not only able to create a unique topographical surface to control cell shape, alignment, cell-cell and cell-matrix contact for basic stem cell biology study, but also could be integrated with 3D bioprinting to generate micropattered 3D structure and thus to induce stem cell based tissue regeneration. ECM coating on a specific topographical structure was capable of inducing even more specific and potent stem cell differentiation along with soluble factors and mechanical force. The article overviews the progress of the past five years in this particular field. PMID- 26836060 TI - Is it Appropriate for Patients to be Discharged at the Scene by Paramedics? AB - BACKGROUND: Outcomes of patients who are discharged at the scene by paramedics are not fully understood. OBJECTIVE: We aimed to describe the risk of re presentation and/or death in prehospital patients discharged at the scene. METHODS: We conducted a retrospective cohort study using linked ambulance, emergency department (ED), and death data. We compared outcomes in patients who were discharged at the scene by paramedics with those who were transported to ED by paramedics and then discharged from ED between January 1 and December 31, 2013 in metropolitan Perth, Western Australia. Occurrences of subsequent ambulance requests, ED attendance, hospital admission and death were compared between those discharged at the scene and those discharged from ED. RESULTS: There were 47,330 patients during the study period, of whom 19,732 and 27,598 patients were discharged at the scene and from ED, respectively. Compared to those discharged from ED, those discharged at the scene were more likely to subsequently: request an ambulance (6.1% vs. 1.8%, adjusted odds ratio [adj OR] 3.4; 95% confidence interval [CI] 3.0-3.9), attend ED (4.6% vs. 1.4%, adj OR 3.3; 95% CI 2.8-3.8), be admitted to hospital (3.3% vs. 0.8%, adj OR 4.2; 95% CI 3.4-5.1). Those discharged at the scene tended towards an increased likelihood of death (0.2% vs. 0.1%, adj OR 1.8; 95% CI 0.99-3.2) within 24 hours of discharge compared to those discharged from ED. CONCLUSION: Patients attended by paramedics who were discharged at the scene had more subsequent events than those who were transported to and discharged from ED. Further consideration needs to be given to who is suitable to be discharged at the scene by paramedics. PMID- 26836062 TI - Effect of Magnetic Field on Photoresponse of Cobalt Integrated Zinc Oxide Nanorods. AB - Cobalt integrated zinc oxide nanorod (Co-ZnO NR) array is presented as a novel heterostructure for ultraviolet (UV) photodetector (PD). Defect states in Co-ZnO NRs surface induces an enhancement in photocurrent as compared to pristine ZnO NRs PD. Presented Co-ZnO NRs PD is highly sensitive to external magnetic field that demonstrated 185.7% enhancement in response current. It is concluded that the opposite polarizations of electron and holes in the presence of external magnetic field contribute to effective separation of electron-hole pairs that have drifted upon UV illumination. Moreover, Co-ZnO NRs PD shows a faster photodetection speed (1.2 s response time and 7.4 s recovery time) as compared to the pristine ZnO NRs where the response and recovery times are observed as 38 and 195 s, respectively. PMID- 26836061 TI - DLX3 negatively regulates osteoclastic differentiation through microRNA-124. AB - Homeodomain gene Distal-less-3 (DLX3) plays an essential role in the development of bones. Mutations of DLX3 are closely associated with Tricho-Dento-Osseous (TDO) syndrome featured with increased bone formation. However, the mechanism regarding whether DLX3 regulates osteoclastogenesis remains largely unknown. In this study, we firstly examined the expression of DLX3 mounting during osteoclastic differentiation process, and then established stably expressing wild type DLX3 (WT-DLX3), a novel mutant DLX3 (Q178R) found in our laboratory recently (MT-DLX3) and Dlx3 knockdown cell lines (Dlx3-shRNA) in Raw 264.7 cells using corresponding lentiviruses. Next, we investigated the influence of DLX3 on these stable cells in the process of osteoclastogenesis. The results showed that the expression of osteoclastogenesis-related genes as well as tartrate-resistant acid phosphatase-positive multinucleated cells were lower in WT-DLX3 and MT-DLX3, but higher in Dlx3-shRNA compared with control cells. Besides, the microRNA-124 expression was higher in WT-DLX3 and MT-DLX3 but lower in Dlx3-shRNA. Moreover, the microRNA-124 expression level positively correlated with DLX3, negatively with osteoclastogenesis-related gene NFATc1. Our results indicate that DLX3 negatively regulates osteoclastic differentiation through microRNA-124, which is partially responsible for the increased bone density in TDO patient. DLX3 may be exploited for osteoclastogenesis regulator and potential therapeutic target of osteoporosis in future. PMID- 26836063 TI - Study of a wheel-like electrorheological finishing tool and its applications to small parts. AB - A wheel-like electrorheological finishing (ERF) tool for small parts polishing is proposed and thoroughly studied. First, the electrorheological polishing fluid is tested, and its properties suggest usability for electrorheological fluid assisted finishing. Then, the mathematical removal model of the ERF tool is built employing the conformal mapping method and high-order multipolar moment theory. Finally, a micropattern of trough is fabricated on a slide glass (7 mm wide and 1 mm thick). The trough is 70 nm deep, and its flat bottom is 1.5 m wide (peak to valley of 3.16 nm and root mean square of 1.27 nm); the surface roughness finally achieves 0.86 nm. The results demonstrate the stable machining capability of the ERF tool for miniature parts. PMID- 26836064 TI - Analysis of intermediary scan-lens and tube-lens mechanisms for optical coherence tomography. AB - Combining an optical coherence tomography (OCT) scanner with other techniques such as optogenetic neurostimulation or fluorescence imaging requires integrating auxiliary components into the optical path of the setup. Due to the short scanning distance of most OCT objectives, adding scan and tube lenses in the device is essential to open space between the back-focal-plane of the objective and center of mass of the mirrors in the galvanometer. The effect of the scan and tube lenses on the focal spot size of the scanner using off-the-shelf components are theoretically explored for three different designs in this paper. Two lens mechanisms were implemented and tested in a custom-built OCT scanner to experimentally measure point-spread functions. Based on our analysis, proper form of a four-element semi-Plossl lens provides a superior performance compared with an achromatic doublet when used as a scan/tube lens. The former lens design provides close to diffraction-limited resolution for scan angles up to 6.4 degrees ; however, due to aberrations in an achromatic doublet, the later design offers diffraction-limited resolution confined to 2 degrees scan angles. PMID- 26836065 TI - Technique of weight factor shifting for aperture averaging. AB - A singular aperture receiver is usually used in a free-space optical communication system. To increase the received optical flux, a larger diameter receiver is preferred, but this approach causes a sharp increase in cost. It also limits the large-scale civil use of free-space optical communications. This paper proposes a technique called aperture averaging weight factor shifting and designs a new type of receiver that can greatly reduce the cost of a free-space optical communication system. This paper offers a comparative analysis of two types of receivers for optical scintillation and proves theoretically that using this new type of receiver does not degrade the performance. PMID- 26836066 TI - Aerosol optical properties in Northern Norway and Svalbard. AB - We present comparisons between estimates of the aerosol optical thickness and the Angstrom exponent in Northern Norway and Svalbard based on data from AERONET (Aerosol Robotic Network) stations at Andenes (69.28 degrees N, 16.01 degrees E, 379 m altitude) and Hornsund (77.00 degrees N, 15.56 degrees E, 10 m altitude) for the period 2008-2013. The five/six-year annual mean values for the aerosol optical thickness at 500 nm tau(500) at Andenes and Hornsund both were 0.09. At Hornsund, there was less variation of the monthly mean value of tau(500) than at Andenes. The annual mean values of the Angstrom exponent alpha at Andenes and Hornsund were 1.29 and 1.34, respectively. At Andenes and Hornsund alpha was found to be larger than 1.1 in 68% and 84% of the observations, respectively, indicating that fine-mode particles were dominating at both sites. Both sites had a similar aerosol size distribution during summer although one site is in an arctic area while the other site is in a subarctic area. PMID- 26836067 TI - Magnetic field sensor using the fiber loop ring-down technique and an etched fiber coated with magnetic fluid. AB - The fiber loop ring-down spectroscopy technique is introduced into the evanescent field-based sensing scheme in order to create a new type of fiber-based magnetic field sensor. As a consequence, the sensitivity and stability of the magnetic field sensing system are significantly enhanced. The sensor head is constructed using a section of a single-mode fiber with its cladding partially etched. The process of fiber etching is described in detail, and the relationship between the diameter of the etched fiber and the etching time is experimentally investigated. After adopting the appropriate size of the etched fiber, the final experimental results show that the magnetic field strength has a well-defined linear relationship with the inverse of the ring-down time tau over a range of 30 mT with a sensitivity of 95.5 ns/mT. PMID- 26836068 TI - New method of attack and security enhancement on an asymmetric cryptosystem based on equal modulus decomposition. AB - A recently proposed asymmetric cryptosystem based on coherent superposition and equal modulus decomposition has shown to be robust against a specific attack. In this paper, we have shown that it is vulnerable to a newly designed attack. With this attack, an intruder is able to access the exact private key and obtain precise attack results using a phase retrieval algorithm. In addition, we have also proposed a security-enhanced asymmetric cryptosystem using a random decomposition technique and a 4f optical system. In the proposed system, random decomposition is employed to create an effective trapdoor one-way function. As a result, it is able to avoid various types of attacks and maintain the asymmetric characteristics of the cryptosystem. Numerical simulations are presented to demonstrate the feasibility and robustness of the proposed method. PMID- 26836069 TI - Design of mirrors for generating prescribed continuous illuminance distributions on the basis of the supporting quadric method. AB - A method for the design of reflecting surfaces generating prescribed continuous illuminance distributions in two-dimensional domains is proposed. The mirror surface is represented as an envelope of a two-parameter family of ellipsoids. The first focus of each ellipsoid coincides with the point light source, while the second one is located at the illuminated domain. This surface representation can be interpreted as a limiting case of a segmented surface used in the supporting quadric method for focusing onto a set of points. The envelope equation depends on the function defining the lengths of the major axes of the ellipsoids of the family. The calculation of this function is performed using a continuous approximation of a discrete function obtained from the solution of a discrete problem of focusing onto a set of points. High efficiency of the proposed method is illustrated by the designed examples of mirrors for generating uniform illuminance distributions in areas of different shapes. PMID- 26836070 TI - Real-time 3D digital image correlation method and its application in human pulse monitoring. AB - In industrial measurements and online monitoring, full-field and high-efficiency deformation analysis has been increasingly important and highly demanded in recent years. In this paper, a fast three-dimensional digital image correlation (3D-DIC) method was proposed to implement real-time measurement. Two improvements were suggested to accelerate the computation speed without sacrificing the accuracy. First, an efficient inverse compositional Gauss-Newton (IC-GN) algorithm was developed to avoid redundant computation. Moreover, a seed point based parallel method was extended for 3D-DIC to achieve parallel computation and faster convergence speed. The detailed process of the real-time measurement using the proposed method was also introduced. Benefiting from the efficient IC-GN algorithm and parallel processing software we developed, full-field, real-time 3D deformation monitoring was realized at a frame rate of 10 frames/s with resolution of 5000 points per frame. For validation, the displacement field of a four-point bending beam was determined by the real-time 3D-DIC. As an application, the real-time human pulse diagnosis was also performed based on the presented technique. Experimental results verify that the proposed real-time 3D DIC is practicable and effective for traditional Chinese medicine. PMID- 26836071 TI - Scattering and absorption coefficients of silica-doped alumina aerogels. AB - Alumina-based aerogels are especially useful in many applications due to their excellent stability at high temperatures. This study experimentally analyzed the radiative properties of silica-doped alumina aerogels through spectral directional-hemispherical measurements for wavelengths of 0.38-25 MUm. The silica doped alumina aerogel samples were prepared with a 1.4?1 molar ratio of silica to alumina. A two-flux model was used to describe the radiation propagation in a 1D scattering absorbing sample to derive expressions for the normal-hemispherical transmittances and reflectances based on the transport approximation. The normal hemispherical transmittances and reflectances were measured at various spectral wavelengths and sample thicknesses using the integrating sphere method. The spectral absorption and transport scattering coefficients of silica-doped alumina aerogels were then determined from the measured normal-hemispherical data. The absorption and transport scattering coefficients of silica-doped alumina aerogels are (0.1 cm-1, 36 cm-1) and (0.1 cm-1, 112 cm-1) for wavelengths of 0.38-8.0 MUm. The spectral transport scattering coefficient varies in the opposite direction from the spectral absorption coefficient for various wavelengths. The radiative properties for silica and alumina aerogels were quite different for the absorption coefficient for wavelengths of 2.5-8.0 MUm and for the transport scattering coefficient for wavelengths of 0.38-2.5 and 3.5-6.0 MUm. The measured radiative properties were used to predict the spectral normal-hemispherical reflectance and transmittance of the silica-doped alumina aerogels for various sample thicknesses and wavelengths. The predicted values do not change for the sample thicknesses greater than a critical value. The analysis provides valuable reference data for alumina aerogels for high-temperature applications. PMID- 26836072 TI - Optical design of the Fresnel lens for LED-driven flashlight. AB - The Fresnel lens is composed of micrometer-sized v-groove structures that determine the maximum illuminance and brightness uniformity of LED-driven flashlights, which are used in high-quality photography. The fabrication quality of the microstructures and the accuracy of the geometrical curvature of the Fresnel lens affect the optical characteristics of the emitted light traveling through the lens, which in turn determines the maximum illuminance and brightness uniformity. This paper presents a systematic design procedure for fabricating the Fresnel lens and investigates the influence of geometrical design and fabrication process on optical performance. The optical analysis was performed using the commercial software TracePro. The results revealed that a small tip radius of the v-groove microstructure facilitates brightness uniformity. Furthermore, both the simulation and the experimental results revealed that Fresnel lenses fabricated through injection molding or injection compression molding have either errors of microstructure height more than 3%-6% or curvature errors higher than 6%, which would affect the optical performance, especially the brightness uniformity. PMID- 26836073 TI - All-optical switching between optical bistability and multistability in a defect dielectric medium doped with a multiple quantum well nanostructure. AB - In this paper, optical bistability (OB) and multistability (OM) properties of a defect dielectric slab are studied. A GsAs multiple quantum well nanostructure (MQW) with 17.5 nm GaAs wells and 15 nm Al(0.3) Ga(0.7) barriers is used in the dielectric medium as a defect layer. Therefore, properties of the refractive index of the slab can be changed in the presence of MQWs. It is observed that switching from OB to OM can be obtained by controlling some external parameters. We find that the exciton spin relaxation and thickness of the slab have essential roles in adjusting the OB and OM properties of the probe light through the slab. Moreover, transmission, reflection, and absorption properties of the propagating pulse through the slab are also discussed. We show that the subluminal and superluminal light transmission or reflection can be obtained via amplification of the probe pulse through the medium. We hope that our proposed model may be suitable for the development of nanoscale devices in all-optical quantum information technology. PMID- 26836074 TI - On the performance of compressed sensing-based methods for millimeter-wave holographic imaging. AB - This paper investigates compressed sensing (CS) based methods for reducing data acquisition time in 2D millimeter-wave holographic imaging systems. Specific attention is paid to situations where the array element spacing does not satisfy the Nyquist criterion due to physical limitations. Simulation and experimental results demonstrate that CS methods achieve better reconstruction than the conventional backpropagation method with undersampled data at the cost of increased computational complexity. Specifically, the definition-based CS (D-CS) method derived by discretizing the scattering model achieves the best image resolution but can produce ghost targets when the sampling interval is greater than approximately twice the Nyquist sampling interval. On the contrary, the Fourier-transform-based CS (FT-CS) method has relatively lower resolution but performs well in the case of low number of measurements, large sampling interval, and low transmit power. In addition, the D-CS method requires much higher time complexity and space complexity than the FT-CS method because the 2D data needs to be processed in vector form. Particularly, the space complexity of constructing and loading the dictionary matrix makes the D-CS method extremely inefficient in dealing with real-time applications. The overall algorithm running time of the D-CS method can be up to 50 times greater than the FT-CS method with a scanning aperture of 81*81 and 121*121 grid size in reconstruction. An efficient method is to use the FT-CS method for coarse imaging and then use the D CS method for specific regions where better precision is required. PMID- 26836075 TI - Miniaturized time-resolved Raman spectrometer for planetary science based on a fast single photon avalanche diode detector array. AB - We present recent developments in time-resolved Raman spectroscopy instrumentation and measurement techniques for in situ planetary surface exploration, leading to improved performance and identification of minerals and organics. The time-resolved Raman spectrometer uses a 532 nm pulsed microchip laser source synchronized with a single photon avalanche diode array to achieve sub-nanosecond time resolution. This instrument can detect Raman spectral signatures from a wide variety of minerals and organics relevant to planetary science while eliminating pervasive background interference caused by fluorescence. We present an overview of the instrument design and operation and demonstrate high signal-to-noise ratio Raman spectra for several relevant samples of sulfates, clays, and polycyclic aromatic hydrocarbons. Finally, we present an instrument design suitable for operation on a rover or lander and discuss future directions that promise great advancement in capability. PMID- 26836076 TI - Focal length calibration of an electrically tunable lens by digital holography. AB - The electrically tunable lens (ETL) is a novel current-controlled adaptive optical component which can continuously tune its focus in a specific range via changing its surface curvature. To quantitatively characterize its tuning power, here we assume the ETL to be a pure phase object and present a novel calibration method to dynamically measure its wavefront by use of digital holographic microscopy (DHM). The least squares method is then used to fit the radius of curvature of the wavefront. The focal length is obtained by substituting the radius into the Zemax model of the ETL. The behavior curve between the focal length of the ETL and its driven current is drawn, and a quadratic mathematic model is set up to characterize it. To verify our model, an ETL and offset lens combination is proposed and applied to ETL-based transport of intensity equation (TIE) phase retrieval microscopy. The experimental result demonstrates the calibration works well in TIE phase retrieval in comparison with the phase measured by DHM. PMID- 26836077 TI - Probability density function of the electric field in diffuse correlation spectroscopy of human bone in vivo. AB - Diffuse correlation spectroscopy (DCS) is the technique of choice for non invasive assessments of human bone blood flow. However, DCS classical algorithms are based on the fundamental assumption that the electric field of the light reaching the DCS photodetector is a zero-mean complex Gaussian variable. The non validity of this hypothesis might produce inaccurate blood flow estimations. It is shown that for the human tibia, the "Gaussian hypothesis" holds for interoptode distances >=20 mm. This lower boundary seems to depend on the type of investigated tissue. PMID- 26836078 TI - Retrieval of water vapor mixing ratio from a multiple channel Raman-scatter lidar using an optimal estimation method. AB - Lidar measurements of the atmospheric water vapor mixing ratio provide an excellent complement to radiosoundings and passive, ground-based remote sensors. Lidars are now routinely used that can make high spatial-temporal resolution measurements of water vapor from the surface to the stratosphere. Many of these systems can operate during the day and night, with operation only limited by clouds thick enough to significantly attenuate the laser beam. To enhance the value of these measurements for weather and climate studies, this paper presents an optimal estimation method (OEM) to retrieve the water vapor mixing ratio, aerosol optical depth profile, Angstrom exponent, lidar constants, detector dead times, and measurement backgrounds from multichannel vibrational Raman-scatter lidars. The OEM retrieval provides the systematic uncertainties due to the overlap function, calibration factor, air density and Rayleigh-scatter cross sections, in addition to the random uncertainties of the retrieval due to measurement noise. The OEM also gives the vertical resolution of the retrieval as a function of height, as well as the height to which the contribution of the a priori is small. The OEM is applied to measurements made by the Meteoswiss Raman Lidar for Meteorological Observations (RALMO) in the day and night for clear and cloudy conditions. The retrieved water vapor mixing ratio is in excellent agreement with both the traditional lidar retrieval method and coincident radiosoundings. PMID- 26836079 TI - Tunable dual-wavelength ytterbium-doped fiber laser using a strain technique on microfiber Mach-Zehnder interferometer. AB - In this paper, stable dual-wavelength generation using a strain technique for a ytterbium-doped fiber laser is successfully demonstrated. A microfiber-based Mach Zehnder interferometer is inserted into the laser ring cavity and stretched using the xyz translation stage. Four sets of dual-wavelength output lasing are obtained when the strain is applied onto a microfiber. The dual-wavelength output possesses spacing between 7.12 and 11.59 nm, with displacement from 2 to 190 MUm from the central wavelength. The obtained side-mode suppression ratio is ~48 dBm, while the maximum power fluctuation and wavelength shift are less than 0.6 dB and 0.01 nm, respectively. The results demonstrate that this setup generates a stable dual-wavelength laser in the 1 MUm region. PMID- 26836080 TI - Imaging of various optical fiber Bragg gratings using differential interference contrast microscopy: analysis and comparison. AB - Differential interference contrast images of various optical fibers and optical fiber Bragg gratings (FBGs), written with the phase mask technique, are presented to provide information about the resultant refractive index variations present in each case. Use of different fiber types using two distinct phase masks producing four Type I FBGs and a Type In FBG allowed similarities and differences in these FBG images due to variations in the Talbot diffraction patterns produced to be studied. PMID- 26836081 TI - Sensor based on macrobent fiber Bragg grating structure for simultaneous measurement of refractive index and temperature. AB - A novel and compact all-fiber sensor based on a macrobent fiber Bragg grating (FBG) structure for simultaneous measurement of refractive index (RI) and temperature is proposed and experimentally investigated. The sensor can be easily fabricated by properly bending an FBG. The bending causes interference between the core mode and the whispering gallery mode, which induces another kind of dip in the transmission spectra of the sensor besides the sharp one of the FBG. Because the two kinds of dips respond differently to the surrounding RI and temperature, these two parameters can be unambiguously measured by the sensor. A sample sensor was fabricated and experimentally investigated, and RI sensitivity of 165.9276 nm/RIU in the range from 1.3330 to 1.3785 and temperature sensitivity of 31.7 pm/ degrees C were achieved. This sensor provides a convenient and economical way for applications where temperature and RI have to be simultaneously measured. PMID- 26836082 TI - Spatial modulation spectroscopy imaging of nano-objects of different sizes and shapes. AB - Spatial modulation spectroscopy (SMS) is a powerful method for interrogating single nanoparticles. In these experiments optical extinction is measured by moving the particle in and out of a tightly focused laser beam. SMS is typically used for particles that are much smaller than the laser spot size. In this paper, we extend the analysis of the SMS signal to particles with sizes comparable to or larger than the laser spot, where the shape of the particle matters. These results are important for the analysis of polydisperse samples that have a wide range of sizes. The presented example images and analysis of a carbon microparticle sample show the utility of the derived expressions. In particular, we show that SMS can be used to generate extinction cross-section information about micrometer-sized particles with complex shapes. PMID- 26836083 TI - Cross-talk compensation of a spatial light modulator for iterative phase retrieval applications. AB - Beam-propagation-based phase recovery approaches, also known as phase retrieval methods, retrieve the amplitude and the phase of arbitrary complex-valued fields. We present and experimentally demonstrate a simple and robust iterative method using a liquid crystal spatial light modulator located at an object diffraction plane. M random phase masks are applied between the object and the image sensor using the modulator, and then M diffraction patterns are collected in the Fourier plane. An iterative algorithm using these patterns and simulating the propagation of the light between the two planes allow us to recover the object wavefront. The use of this type of dynamic modulator makes the experimental setup simpler and more flexible. We need no a priori knowledge about the object field, and the convergence rate is high. Simulation results show that the method exhibits high immunity to noise and does not suffer any stagnation problem. However, experimental results have shown that the technique is sensitive to the cross talk of the modulator. We propose a method for compensating these modulator defects that are validated by experimental results. PMID- 26836084 TI - All-plastic fiber-based pressure sensor. AB - We present a feasibility study and a prototype of an all-plastic fiber-based pressure sensor. The sensor is based on long period gratings inscribed for the first time to the best of our knowledge by a CO2 laser in polymethyl methacrylate (PMMA) microstructured fibers and coupled to a pod-like transducer that converts pressure to strain. The sensor prototype was characterized for pressures up to 150 mbars, and various parameters related to its construction were also characterized in order to enhance sensitivity. We consider this sensor in the context of future applications in endoscopic pressure sensors. PMID- 26836085 TI - Study of thermal decomposition mechanisms and absorption cross section of nitro rich phenyl- and bis-series 1,2,3-triazoles. AB - This paper reports the investigation of thermal decomposition mechanisms and evaluation of thermally released NO2 from two newly synthesized high-energy materials named 1-(4-nitrophenyl)-1H-1,2,3-triazole (S8) and 2,6-bis ((4 (nitromethyl)-1H-1,2,3-triazol-1-yl)methyl) pyridine (S9) using time-resolved pulsed photoacoustic (PA) pyrolysis technique. The PA spectra were recorded between the 30 degrees C and 350 degrees C range and by varying the pressure of compounds vapor using 532 nm wavelength of pulse duration 7 ns at 10 Hz repetition rate obtained from Q-switched Nd:YAG laser pulses. The PA results were cross verified with thermogravimetric-differential thermal analysis data. The quality factor "&=&Q"&=& of the PA cavity was measured to test the thermal stability of the compound. In addition, we have ascertained the molecular density, absorption cross sections of high-energy materials vapor in terms of NO2. The corresponding values are of the order of 0.1-1.2*10(20) cm-3 and 0.5-6 kilobarn, respectively. These results once again confirm the close agreement between the radiative and nonradiative transitions data and established the role of NO2 during the thermal decomposition process. PMID- 26836086 TI - Use of single-negative material as a tunable defect in a dielectric photonic crystal heterostructure. AB - The defect mode in a photonic crystal heterostructure of (1/2) N (2/1)N tuned by using a single-negative layer as a defect layer; that is, the structure to be considered is (1/2)ND (2/1)N, where 1, 2 are dielectrics, N is the stack number, and D is a defect layer taken to be a single-negative material. The results show that when D is a mu-negative (MU < 0) medium, the defect mode frequency is redshifted as a function of the thickness of D as well as the static permittivity. On the other hand, if D is an epsilon-negative (epsilon < 0) medium, the defect mode frequency is blueshifted as the defect layer thickness increases, but it is independent of the static permeability. We also investigate the angular dependence of the defect frequency for both two polarizations, transverse electric (TE) wave and transverse magnetic (TM) wave. The defect mode frequency is shown to be blueshifted as a function of the angle of incidence. Additionally, the shift in the TE wave is larger than that in the TM wave. PMID- 26836087 TI - Generating long sequences of high-intensity femtosecond pulses. AB - We present an approach to creating pulse sequences extending beyond 150 ps in duration, comprised of 100 MUJ femtosecond pulses. A quarter of the pulse train is produced by a high-resolution pulse shaper, which allows full controllability over the timing of each pulse. Two nested Michelson interferometers follow to quadruple the pulse number and the sequence duration. To boost the pulse energy, the long train is sent through a multipass Ti:sapphire amplifier, followed by an external compressor. A periodic sequence of 84 pulses of 120 fs width and an average pulse energy of 107 MUJ, separated by 2 ps, is demonstrated as a proof of principle. PMID- 26836088 TI - Optical properties of lithium terbium fluoride and implications for performance in high power lasers. AB - LiTbF4 has the potential to replace traditional magneto-optic garnet materials as a Faraday rotator in high power laser systems due to its high Verdet constant. New measurements are reported of the ordinary and extraordinary refractive indices of LiTbF4 as functions of wavelength and temperature, respectively, as well as their corresponding Sellmeier expressions. Consequently, the Verdet coefficient was calculated and plotted as a function of wavelength and temperature. These measurements will aid in further development of LiTbF4 as an optical isolator. PMID- 26836089 TI - Natural dye extracted from karkadah and its application in dye-sensitized solar cells: experimental and density functional theory study. AB - This work presents an experimental and theoretical study of cyanidin natural dye as a sensitizer for ZnO dye-sensitized solar cells. ZnO nanoparticles were prepared using ammonia and oxalic acid as a capping agent. The calculated average size of the synthesized ZnO with different capping agents was found to be 32.1 nm. Electronic properties of cyanidin and delphinidin dye were studied using density functional theory (DFT) and time-dependent DFT with a B3LYP/6-31G(d,p) level. By comparing the theoretical results with the experimental data, the cyanidin dye can be used as a sensitizer in dye-sensitized solar cells. An efficiency of 0.006% under an AM-1.5 illumination at 100 mW/cm(2) was attained. The influence of dye adsorption time on the solar cell performance is discussed. PMID- 26836090 TI - Phase stepping optical profilometry using fiber optic Lloyd's mirrors. AB - A three-step phase stepping profilometry based on a fiber optic Lloyd's mirror assembly is employed in the optical profilometry for the first time to measure the shapes of 3D objects. Required pi/2 phase shifts for interference fringe pattern are obtained by mechanically sliding the Lloyd assembly via an ordinary micrometer stage. The experimental setup is simple and low cost to construct, and is insensitive to the ambient temperature fluctuations and environmental vibrations that cause unwanted effects on the projected fringe pattern. Consecutive interferograms are captured by a CCD camera and are processed with an algorithm to accomplish 3D topographies. PMID- 26836091 TI - Numerical simulation of laser focusing properties inside birefringent crystal. AB - The transmission properties of a focused laser inside anisotropic material are complex due to the birefringent effect, which has remarkable influence on the light distribution and frequency multiplication efficiency of crystals. Meanwhile, it will also affect the laser micromachining precision of birefringent materials with random polarization. In this study, ray tracing and diffraction integral methods were proposed to develop the mathematical model of a laser focused through an isotropic medium into a KDP crystal. Using these models, the focusing properties and 3D light intensity distribution of a focused laser inside a KDP crystal at different orientations were investigated. The research shows that the size and shape of the E-ray focus will distort, and its peak power density decreases rapidly with the decrease of the angle between the optical axis and the crystal surface. Meanwhile, the focal position of the E-ray will also move with the change of optical axis orientation. Based on the simulated results, an approximate 3D light intensity equation of a laser focused into birefringent material was also proposed, which is in good agreement with the theoretical analysis. The related simulated results have an important engineering value for nonlinear optics and laser processing of birefringent materials. PMID- 26836092 TI - Coherent beam combining in atmospheric channels using gated backscatter. AB - This paper introduces the concept of atmospheric channels and describes a possible approach for the coherent beam combining of lasers of an optical phased array (OPA) in a turbulent atmosphere. By using the recently introduced sparse spectrum harmonic augmentation method, a comprehensive simulative investigation was performed and the exceptional properties of the atmospheric channels were numerically demonstrated. Among the interesting properties are the ability to guide light in a confined manner in a refractive channel, the ability to gather different sources to the same channel, and the ability to maintain a constant relative phase within the channel between several sources. The newly introduced guiding properties combined with a suggested method for channel probing and phase measurement by aerosol backscattered radiation allows coherence improvement of the phased array's elements and energy refocusing at the location of the channel in order to increase power in the bucket without feedback from the target. The method relies on the electronic focusing, electronic scanning, and time gating of the OPA, combined with elements of the relative phase measurements. PMID- 26836093 TI - Evaluation of a linear birefringence measurement method with increased sensitivity. AB - The evaluation of a measurement method of linear birefringence with increased sensitivity is presented. The examined method is based on a substantial change of the geometrical phase caused by a small change of an examined medium's birefringence. The measuring setup consists of a linear polarizer, Wollaston compensator, and circular analyzer. The measurement is performed by tracking the phase shift of a fringe pattern. Specific orientation of the elements modifies the setup's response-the sensitivity of the setup can be controlled in a limited measuring range. The present paper concentrates on the factors affecting the setup's sensitivity as well as the accuracy of obtained results. The validity of the proposed approach has been demonstrated by measuring a phase retardance introduced by the liquid crystal retarder. A thousandfold increase in sensitivity has been obtained in the presented experiments, which allows the measurement of retardance introduced by the linear birefringent medium with an accuracy of 0.003 degrees within the limited measuring range. PMID- 26836094 TI - Modeling and analysis of the thermal effects of a circular bimorph piezoelectric actuator. AB - A theoretical analysis of the thermal effects of a circular bimorph piezoelectric actuator (CBPA) was performed. The circular bimorph structure consists of two flexible piezoelectric ceramic layers and one metallic layer in the middle, and is powered to produce flexural deformation. The CBPA, which may be a good match for large adaptive optics telescopes, has a large stroke and a high resonance frequency. We have derived analytical solutions (both the static solution and the dynamic solution) of the thermal effects of introducing (and increasing the thickness of) a metallic layer into the bimorph. Numerical results are presented to illustrate the dependence of the CBPA's performance upon the physical parameters. PMID- 26836095 TI - Power-ratio tunable dual-wavelength laser using linearly variable Fabry-Perot filter as output coupler. AB - For a linearly variable Fabry-Perot filter, the peak transmission wavelengths change linearly with the transverse position shift of the substrate. Such a Fabry Perot filter is designed and fabricated and used as an output coupler of a c-cut Nd:YVO4 laser experimentally in this paper to obtain a 1062 and 1083 nm dual-wavelength laser. The peak transmission wavelengths are gradually shifted from 1040.8 to 1070.8 nm. The peak transmission wavelength of the Fabry-Perot filter used as the output coupler for the dual-wavelength laser is 1068 nm and resides between 1062 and 1083 nm, which makes the transmissions of the desired dual wavelengths change in opposite slopes with the transverse shift of the filter. Consequently, powers of the two wavelengths change in opposite directions. A branch power, oppositely tunable 1062 and 1083 nm dual-wavelength laser is successfully demonstrated. Design principles of the linear variable Fabry-Perot filter used as an output coupler are discussed. Advantages of the method are summarized. PMID- 26836096 TI - Resolution enhancement of surface plasmon resonance sensors with spectral interrogation: resonant wavelength considerations. AB - Surface plasmon resonance (SPR) has been used extensively in biosensing implementation as a high-sensitivity and label-free sensing technique. For SPR sensors based on spectral interrogation, their performance in terms of refractive index (RI) resolution differs substantially when operating at different resonant wavelengths. This paper presents a feasible scheme of enhancing the sensor resolution by simulating measured SPR curves using an experiment-assisted simulation model to effectively explore the optimal resonant wavelength for the sensing system. It shows that the variation of experimentally obtained RI resolution with the resonant wavelength is in good accordance with the simulation results. In addition, the RI resolution at the derived optimal resonant wavelength is at least 2 times better than that at the commonly used resonant wavelength region both experimentally and theoretically. The methods of the proposed scheme potentially facilitate optimization of various sensor instrumentation for high-resolution SPR sensing. PMID- 26836097 TI - Magnetic-field-compensation optical vector magnetometer. AB - A concept for an optical magnetometer used for the measurement of magnitude and direction of a magnetic field (B-field) in two orthogonal directions is developed based on double scanning of a B-field to compensate the measured field to zero value, which is monitored by a resonant magneto-optical process in an unshielded atomic vapor cell. Implementation of the technique using the nonlinear Hanle effect on the D2 line of rubidium demonstrates viability and efficiency of the proposed concept. The ways to enhance characteristics of the suggested technique and optimize its performance, as well as the possible extension to three-axis magnetometry, are discussed. PMID- 26836098 TI - Defocus and geometric distortion correction for projected images on a curved surface. AB - In this paper, a correction method of defocus and geometric distortion for projected images on nonideal projection surfaces is proposed. To offer distortion free images on curved projection surfaces, a camera captures the projected image to estimate the distortion. To compensate for defocus, which is due to the change in distance from the projector to the projection surface, the space varying point spread function of the projector is modeled using a thin lens model. The performance of the proposed algorithm is verified from experiments when the projection surface is curved; the defocus is compensated for using the space varying point-spread function while correcting for the geometric distortion. Employing a point-spread function model, which depends on the distance from the projector to the projection surface, is quite simple and accurate; therefore, a focused image could be obtained using space varying deconvolution. The aim of our proposed method is for application to mobile projectors. PMID- 26836099 TI - Tunable sensitivity phase detection of transmitted-type dual-channel guided-mode resonance sensor based on phase-shift interferometry. AB - This paper reports on a transmitted-type dual-channel guided-mode resonance (GMR) sensor system that uses phase-shifting interferometry (PSI) to achieve tunable phase detection sensitivity. Five interference images are captured for the PSI phase calculation within ~15 s by using a liquid crystal retarder and a USB web camera. The GMR sensor structure is formed by a nanoimprinting process, and the dual-channel sensor device structure for molding is fabricated using a 3D printer. By changing the rotation angle of the analyzer in front of the camera in the PSI system, the sensor detection sensitivity can be tuned. The proposed system may achieve high throughput as well as high sensitivity. The experimental results show that an optimal detection sensitivity of 6.82*10(-4) RIU can be achieved. PMID- 26836100 TI - Simple ray-tracing model for a rough surface of an ink layer including internal scattering particles printed on a light guide plate. AB - For simulating light guide lighting systems, we have developed a ray-tracing model for an ink layer extracting light from a light guide. The model consists of the volume and the rough surface scattering calculated on the basis of Mie theory and the facet model, respectively. The model of an ink layer was required to conserve energy for analyzing how much light loss occurs in each component in the lighting system. Though a single-scattering rough surface model with a shadowing/masking function successfully describes the scattering distribution, shadowing light violates the energy conservation law because of a lack of multiple scattering. We developed the rough surface ray-tracing model (RSRT model), which includes the multiple scattering instead of the shadowing/masking effect. We investigated the applicability of the RSRT model for an ink layer by comparing the RSRT model with recent physical and facet models. Finally, we compared the calculated and measured scattering distributions of an ink layer, applied the developed ink layer model to the lighting system, and confirmed the developed model to be valid. PMID- 26836101 TI - Development of an improved data analysis approach for combined laser extinction and two-angle elastic light scattering diagnostics of soot aggregates. AB - An improved data analysis approach has been developed for the combined laser extinction and two-angle elastic light scattering diagnostics to relate the various measured optical cross sections to soot aggregate properties. The performance of the proposed approach is assessed using the comprehensive dataset of Santoro ethylene-air co-flow diffusion flame. Compared to previously reported studies, the proposed approach can be applied to a wider range of soot sources by removing the assumption made to the scattering regime or moment ratio of aggregate size distribution. The proposed approach also considers the contribution of scattering to extinction in determining the soot volume fraction, and this contribution is shown to increase as soot aggregate size becomes larger. The sensitivity of the calculation to the assumed parameters of the approach is examined and discussed. The mean radius of gyration of soot aggregates and the ratio of scattering intensities at the two measurement angles are shown to be independent of soot refractive index and are therefore recommended for soot model validation purposes. PMID- 26836102 TI - Pump polarization insensitive and efficient laser-diode pumped Yb:KYW ultrafast oscillator. AB - We theoretically and experimentally report and evaluate a novel split laser-diode (LD) double-end pumped Yb:KYW ultrafast oscillator aimed at improving the performance of an ultrafast laser. Compared to a conventional unpolarized single LD end-pumped ultrafast laser system, we improve the laser performance such as absorption efficiency, slope efficiency, cw mode-locking threshold, and output power by this new structure LD-pumped Yb:KYW ultrafast laser. Experiments were carried out with a 1 W output fiber-coupled LD. Experimental results show that the absorption increases from 38.7% to 48.4%, laser slope efficiency increases from 18.3% to 24.2%, cw mode-locking threshold decreases 12.7% from 630 to 550 mW in cw mode-locking threshold, and maximum output-power increases 28.5% from 158.4 to 221.5 mW when we switch the pump scheme from an unpolarized single-end pumping structure to a split LD double-end pumping structure. PMID- 26836103 TI - Restraint of path effect on optical surface in magnetorheological jet polishing. AB - Path effect on a polished surface always matches tool motions and manifests as mid-spatial frequency (MSF) errors in magnetorheological jet polishing processing. To control the path effect, extended methods and part-constrained paths are presented in this paper. The extended methods, Zernike extension and Neighbor-Gerchberg extension, are developed for building an extended surface with a weak edge effect in simulation. Under the constraint of the pitch principle, the unicursal part-constrained path is presented to enhance the randomness of the tool path, including path turns and dwell-point positions. Experiments are executed to validate the effectiveness of these measures for diminishing MSF errors. The peak to valley and root mean square of the surface are improved from 0.220lambda and 0.047lambda (lambda=632.8 nm) to 0.064lambda and 0.007lambda, respectively, while simultaneously restricting the path effect. PMID- 26836104 TI - Magnetic-field tunable multichannel filter in a plasma photonic crystal at microwave frequencies. AB - The microwave magnetic-field tunable filtering properties in a multichannel filter based on use of a one-dimensional finite magnetized plasma photonic crystal (PPC) are theoretically investigated. The considered PPC has a structure of air/(AB)N/air, where A is a dielectric layer, B is a plasma layer, and N is the stack number. First, in the absence of an externally applied magnetic field, the structure can work as a multichannel filter whose channel number is equal to N-1 for N>1. Next, in the presence of an externally applied field, the filtering properties become tunable, i.e., the channel frequencies can be shifted as a function of the applied magnetic field. We find that the effect of the magnetic field will cause the channel frequencies to be blue-shifted or red-shifted depending on the orientation of the applied magnetic field. PMID- 26836105 TI - Refractive indices of common solvents and solutions at 1550 nm. AB - Using a large-angle refractometer, the refractive indices of water, methanol, acetonitrile, acetone, ethanol, formaldehyde solution, 2-propanol, hexanes, 1 propanol, 2-butanol, tetrahydrofuran, dichloromethane, 1,4-dioxane, cyclohexane, N,N-dimethylformamide, ethylene glycol, N,N-dimethylacetamide, chloroform, glycerol, trichloroethylene, dimethylsulfoxide, p-xylene, ethylbenzene, toluene, m-xylene, benzene, and o-xylene were measured at 1550 nm and compared to literature values. In addition, the refractive indices of 48 aqueous sucrose solutions, 34 aqueous sodium chloride solutions, 40 DMSO-water, 40 ethylene glycol-water, and 40 glycerol-water mixtures were also measured at different concentrations and fit with third-order polynomial expressions. This study provides near-infrared refractive indices that were not previously available and may help with the calibration of refractive index sensors that operate at or near 1550 nm. PMID- 26836107 TI - Effects of cell phone radiation on lipid peroxidation, glutathione and nitric oxide levels in mouse brain during epileptic seizure. AB - The objective of the this study was to evaluate the effects of cellular phone radiation on oxidative stress parameters and oxide levels in mouse brain during pentylenetetrazole (PTZ) induced epileptic seizure. Eight weeks old mice were used in the study. Animals were distributed in the following groups: Group I: Control group treated with PTZ, Group II: 15min cellular phone radiation+PTZ treatment+30min cellular phone radiation, Group III: 30min cellular phone radiation+PTZ treatment+30min cellular phone radiation. The RF radiation was produced by a 900MHz cellular phone. Lipid peroxidation, which is the indicator of oxidative stress was quantified by measuring the formation of thiobarbituric acid reactive substances (TBARS). The glutathione (GSH) levels were determined by the Ellman method. Tissue total nitric oxide (NOx) levels were obtained using the Griess assay. Lipid peroxidation and NOx levels of brain tissue increased significantly in group II and III compared to group I. On the contrary, GSH levels were significantly lower in group II and III than group I. However, no statistically significant alterations in any of the endpoints were noted between group II and Group III. Overall, the experimental findings demonstrated that cellular phone radiation may increase the oxidative damage and NOx level during epileptic activity in mouse brain. PMID- 26836108 TI - Insuring against health shocks: Health insurance and household choices. AB - This paper provides empirical evidence on the role of public health insurance in mitigating adverse outcomes associated with health shocks. Exploiting the rollout of a universal health insurance program in rural China, I find that total household income and consumption are fully insured against health shocks even without access to health insurance. Household labor supply is an important insurance mechanism against health shocks. Access to health insurance helps households to maintain investment in children's human capital during negative health shocks, which suggests that one benefit of health insurance could arise from reducing the use of costly smoothing mechanisms. PMID- 26836109 TI - Spin-Orbit Effects in Closed-Shell Heavy and Superheavy Element Monohydrides and Monofluorides with Coupled-Cluster Theory. AB - Bond lengths and force constants of a set of closed-shell sixth-row and superheavy element monohydrides and monofluorides are calculated in this work. Kramers restricted coupled-cluster approaches (KR-CC) with spin-orbit coupling (SOC) included at the self-consistent field (SCF) level as well as CC approaches with SOC included in post-SCF treatment (SOC-CC) are employed in calculations. Recently published relativistic effective core potentials are employed, and highly accurate results for superheavy element molecules are achieved with KR CCSD(T). SOC effects on bond lengths and force constants of these molecules are investigated. Effects of electron correlation are shown to be affected by SOC to a large extent for some superheavy element molecules. Bond lengths and force constants with SOC-CC agree very well with those of KR-CC for most of the sixth row element molecules. As for superheavy element molecules, SOC-CCSD is able to afford results that are in good agreement with those of KR-CCSD except for 111F, while the error of SOC-CCSD(T) is more pronounced. Large error would be encountered with SOC-CC approaches for molecules when both SOC and electron correlation effects are sizable. PMID- 26836110 TI - Oxygen Vacancy-Induced Structural, Optical, and Enhanced Supercapacitive Performance of Zinc Oxide Anchored Graphitic Carbon Nanofiber Hybrid Electrodes. AB - Zinc oxide (ZnO) nanoparticles (NPs) anchored to carbon nanofiber (CNF) hybrids were synthesized using a facile coprecipitation method. This report demonstrates an effective strategy to intrinsically improve the conductivity and supercapacitive performance of the hybrids by inducing oxygen vacancies. Oxygen deficiency-related defect analyses were performed qualitatively as well as quantitatively using Fourier transform infrared spectroscopy, energy-dispersive X ray spectroscopy, and X-ray photoelectron spectroscopy. All of the analyses clearly indicate an increase in oxygen deficiencies in the hybrids with an increase in the vacuum-annealing temperature. The nonstoichiometric oxygen vacancy is mainly induced via the migration of the lattice oxygen into interstitial sites at elevated temperature (300 degrees C), followed by diffusion into the gaseous phase with further increase in the annealing temperature (600 degrees C) in an oxygen-deficient atmosphere. This induction of oxygen vacancy is corroborated by diffuse reflectance spectroscopy, which depicts the oxygen-vacancy-induced bandgap narrowing of the ZnO NPs within the hybrids. At a current density of 3 A g(-1), the hybrid electrode exhibited higher energy density (119.85 Wh kg(-1)) and power density (19.225 kW kg(-1)) compared to a control ZnO electrode (48.01 Wh kg(-1) and 17.687 kW kg(-1)). The enhanced supercapacitive performance is mainly ascribed to the good interfacial contact between CNF and ZnO, high oxygen deficiency, and fewer defects in the hybrid. Our results are expected to provide new insights into improving the electrochemical properties of various composites/hybrids. PMID- 26836111 TI - Two dimensional IR-FID-CPMG acquisition and adaptation of a maximum entropy reconstruction. AB - By acquiring the FID signal in two-dimensional TD-NMR spectroscopy, it is possible to characterize mixtures or complex samples composed of solid and liquid phases. We have developed a new sequence for this purpose, called IR-FID-CPMG, making it possible to correlate spin-lattice T1 and spin-spin T2 relaxation times, including both liquid and solid phases in samples. We demonstrate here the potential of a new algorithm for the 2D inverse Laplace transformation of IR-FID CPMG data based on an adapted reconstruction of the maximum entropy method, combining the standard decreasing exponential decay function with an additional term drawn from Abragam's FID function. The results show that the proposed IR-FID CPMG sequence and its related inversion model allow accurate characterization and quantification of both solid and liquid phases in multiphasic and compartmentalized systems. Moreover, it permits to distinguish between solid phases having different T1 relaxation times or to highlight cross-relaxation phenomena. PMID- 26836112 TI - Economic and Quality of Life Benefits of Anti-VEGF Therapy. AB - Vision impairment and blindness create a significant impact on quality of life and loss of productivity. Health care expenditures for vision problems, including direct medical costs and indirect costs for support services and loss of productivity, amount to $139 billion annually. It is projected that by 2020, five million people will have visual impairment due to age related macular degeneration and diabetic macular edema. VEGF inhibitor therapy has been shown to be a cost-effective treatment for age related macular degeneration and diabetic macular edema that has reduced the incidence of vision loss and can reduce the associated economic and societal cost. PMID- 26836119 TI - Synthesis of 1,2-Disubstituted Indoles from alpha-Aminonitriles and 2-Halobenzyl Halides. AB - The alpha-alkylation of deprotonated Strecker products derived from primary amines and aromatic aldehydes with 2-halobenzyl halides furnishes intermediates that can be cyclized to 1,2-disubstituted indoles in moderate to high yields (up to 94% over two steps) by microwave-assisted copper- or palladium-catalyzed intramolecular cross-coupling. PMID- 26836117 TI - Exosome-associated AAV vector as a robust and convenient neuroscience tool. AB - Adeno-associated virus (AAV) vectors are showing promise in gene therapy trials and have proven to be extremely efficient biological tools in basic neuroscience research. One major limitation to their widespread use in the neuroscience laboratory is the cost, labor, skill and time-intense purification process of AAV. We have recently shown that AAV can associate with exosomes (exo-AAV) when the vector is isolated from conditioned media of producer cells, and the exo-AAV is more resistant to neutralizing anti-AAV antibodies compared with standard AAV. Here, we demonstrate that simple pelleting of exo-AAV from media via ultracentrifugation results in high-titer vector preparations capable of efficient transduction of central nervous system (CNS) cells after systemic injection in mice. We observed that exo-AAV is more efficient at gene delivery to the brain at low vector doses relative to conventional AAV, even when derived from a serotype that does not normally efficiently cross the blood-brain barrier. Similar cell types were transduced by exo-AAV and conventionally purified vector. Importantly, no cellular toxicity was noted in exo-AAV-transduced cells. We demonstrated the utility and robustness of exo-AAV-mediated gene delivery by detecting direct GFP fluorescence after systemic injection, allowing three dimensional reconstruction of transduced Purkinje cells in the cerebellum using ex vivo serial two-photon tomography. The ease of isolation combined with the high efficiency of transgene expression in the CNS, may enable the widespread use of exo-AAV as a neuroscience research tool. Furthermore, the ability of exo-AAV to evade neutralizing antibodies while still transducing CNS after peripheral delivery is clinically relevant. PMID- 26836118 TI - The induction of antigen-specific CTL by in situ Ad-REIC gene therapy. AB - An adenovirus vector carrying the human Reduced Expression in Immortalized Cell (REIC)/Dkk-3 gene (Ad-REIC) mediates simultaneous induction of cancer-selective apoptosis and augmentation of anticancer immunity. In our preclinical and clinical studies, in situ Ad-REIC gene therapy showed remarkable direct and indirect antitumor effects to realize therapeutic cancer vaccines. We herein aimed to confirm the induction of tumor-associated antigen-specific cytotoxic T lymphocytes (CTLs) by Ad-REIC. Using an ovalbumin (OVA), a tumor-associated antigen, expressing E.G7 tumor-bearing mouse model, we investigated the induction and expansion of OVA-specific CTLs responsible for indirect, systemic effects of Ad-REIC. The intratumoral administration of Ad-REIC mediated clear antitumor effects with the accumulation of OVA-specific CTLs in the tumor tissues and spleen. The CD86-positive dendritic cells (DCs) were upregulated in the tumor draining lymph nodes of Ad-REIC-treated mice. In a dual tumor-bearing mouse model in the left and right back, Ad-REIC injection in one side significantly suppressed the tumor growth on both sides and significant infiltration of OVA specific CTLs into non-injected tumor was also detected. Consequently, in situ Ad REIC gene therapy is expected to realize a new-generation cancer vaccine via anticancer immune activation with DC and tumor antigen-specific CTL expansion. PMID- 26836121 TI - Achieving Reversible Sensing of Nitroxyl by Tuning the Ligand Environment of Azamacrocyclic Copper(II) Complexes. AB - To elucidate the factors that impart selectivity for nitroxyl (HNO) over nitric oxide (NO), thiols, and H2S in metal-based fluorescent probes, we investigated five Cu(II)-cyclam (14-N4) derivatives. Upon exposure to NO gas at pH 7, no changes occur in the UV-vis spectra of any of the complexes. Addition of Angeli's salt to generate HNO promotes reduction of Cu(II) only in the case of [Cu(II)(14 N4-Ts)(OTf)2], which has the most positive reduction potential of the series. To gain insight into the observed reactivity, we prepared the Cu(II) complex of the mixed thia/aza 14-N2S2 ligand. [Cu(II)(14-N2S2)(OTf)2] reacts reversibly with HNO at pH 7, although nonselectively over thiols and H2S. The recurrent sensing of HNO uncovered with the study of Cu(II) azamacrocyclic complexes is a remarkable feature that opens the door for the design of a new generation of metal-based probes. PMID- 26836120 TI - Microvesicles from Mesenchymal Stromal Cells Are Involved in HPC-Microenvironment Crosstalk in Myelodysplastic Patients. AB - Exosomes/microvesicles (MVs) provide a mechanism of intercellular communication. Our hypothesis was that mesenchymal stromal cells (MSC) from myelodysplastic syndrome (MDS) patients could modify CD34+ cells properties by MVs. They were isolated from MSC from MDS patients and healthy donors (HD). MVs from 30 low-risk MDS patients and 27 HD were purified by ExoQuick-TCTM or ultracentrifugation and identified by transmission electron microscopy, flow cytometry (FC) and western blot for CD63. Incorporation of MVs into CD34+ cells was analyzed by FC, and confocal and fluorescence microscopy. Changes in hematopoietic progenitor cell (HPC) properties were assessed from modifications in microRNAs and gene expression in CD34+ cells as well as viability and clonogenic assays of CD34+ cells after MVs incorporation. Some microRNAs were overexpressed in MVs from patients MSC and two of them, miR-10a and miR-15a, were confirmed by RT-PCR. These microRNAs were transferred to CD34+ cells, modifying the expression of MDM2 and P53 genes, which was evaluated by RT-PCR and western blot. Finally, examining CD34+ cells properties after incorporation, higher cell viability (p = 0.025) and clonogenic capacity (p = 0.037) were observed when MVs from MDS patients were incorporated. In summary, we show that BM-MSC release MVs with a different cargo in MDS patients compared with HD. These structures are incorporated into HPC and modify their properties. PMID- 26836123 TI - Sensing of nutrients and microbes in the gut. AB - PURPOSE OF REVIEW: Sensing of nutrients and microbes in the gut are fundamental processes necessary for life. This review aims to provide an overview of the basic background and new data on cellular nutrient, energy, and microbe sensors. RECENT FINDINGS: The nutrient sensors 5' adenosine monophosphate-activated protein kinase, activating transcription factor 4 and mechanistic target of rapamycin (mTOR) are critical in control of the cell cycle. Recent data demonstrate their role in metabolic syndrome, in cell growth, and as therapeutic targets. Regulation of mTOR by the amino acids is the subject of intense investigation. Recent studies have further elucidated the exact mechanism of amino acid-dependent mTOR regulation. Pathogen recognition receptors (PRRs) are receptors that recognize conserved microbial molecules. New data demonstrate how lymphocyte-specific PRRs are necessary to maintain homeostasis. Moreover, new studies explore the role of PRRs in controlling the gut bacterial and fungal microbiome. SUMMARY: Nutrient sensing molecules are central to cell growth and metabolism and are implicated in cancer and the metabolic syndrome. Regulation of nutrient sensors is complex, and may be amenable to therapeutic targeting. Microbial sensors play critical roles in homeostasis and maintenance of the gut fungal and bacterial microbiome. PMID- 26836122 TI - One-Step Synthesis of MoS2/WS2 Layered Heterostructures and Catalytic Activity of Defective Transition Metal Dichalcogenide Films. AB - Transition metal dichalcogenides (TMDCs) are a promising class of two-dimensional (2D) materials for use in applications such as 2D electronics, optoelectronics, and catalysis. Due to the van der Waals (vdW) bonding between layers, vdW heterostructures can be constructed between two different species of TMDCs. Most studies employ exfoliation or co-vapor growth schemes, which are limited by the small size and uneven distribution of heterostructures on the growth substrate. In this work we demonstrate a one-step synthesis procedure for large-area vdW heterostructures between horizontal TMDCs MoS2 and WS2. The synthesis procedure is scalable and provides patterning ability, which is critical for electronic applications in integrated circuits. We demonstrate rectification characteristics of large-area MoS2/WS2 stacks. In addition, hydrogen evolution reaction performance was measured in these horizontal MoS2 and WS2 thin films, which indicate that, in addition to the catalytically active sulfur edge sites, defect sites may serve as catalyst sites. PMID- 26836124 TI - Endothelium-Dependent and -Independent Vasodilator Effects of Dimethyl Sulfoxide in Rat Aorta. AB - This study examined the mechanism of vasorelaxation induced by dimethyl sulfoxide (DMSO) in endothelium-intact and -denuded rat aorta. DMSO (0.1-3%) inhibited phenylephrine (PE, 1 MUmol/l)-induced contraction in a dose-dependent manner. However, this relaxation was lower in the absence of the endothelium. Increase in DMSO-induced relaxation in the presence of the endothelium was attenuated by preincubation in L-NG-nitroarginine methyl ester (L-NAME, 100 MUmol/l) and by the removal of the endothelium. In the aorta with endothelium, DMSO (3%) and CCh (3 MUmol/l) increased cGMP contents, significantly and L-NAME (100 MUmol/l) inhibited the DMSO-induced increases of cGMP. In fura 2-loaded endothelium denuded aorta, cumulative application of DMSO (1-3%) inhibited PE-induced muscle tension; however, this application did not affect the [Ca2+]i level. In PE precontracted endothelium-denuded aorta, relaxation responses to fasudil were significantly less in the presence of DMSO compared to the control. These results suggest that DMSO causes relaxation by increasing the cGMP content in correlation with the release of NO from endothelial cells and by decreasing the Ca2+ sensitivity of contractile elements partly via inhibiting Rho-kinase in rat aorta. PMID- 26836125 TI - Anatomical Remodeling of Buccal Bone Plate in 35 Premaxillary Post-Extraction Immediately Restored Single TPS Implants: 10-Year Radiographic Investigation. AB - PURPOSE: The anatomical remodeling technique (ART) was proposed to place postextraction implants with the aid of specific osteotomes. This study is a clinical and radiographic evaluation with 10-year follow-up of anterior postextraction single implants placed with the ART and immediately restored. MATERIALS AND METHODS: Thirty-five patients, with a hopeless tooth in the anterior maxilla, were included in the study and 35 implants were inserted according to the ART. Clinical and radiographic evaluations were performed at baseline (T0), after 6 (T1) and 14 months (T2), 4 years after surgery (T3) and every other year up to the 10-year follow-up (T4, T5, and T6). Implant success, survival, and failure rates were evaluated according to the International Congress of Oral Implantologists Pisa Consensus Conference criteria. RESULTS: Twenty-nine patients and 29 implants were available for the 10-year data analysis. After 10 years, the accumulated mean marginal bone loss was 2.69 +/- 0.42 mm. The cumulative survival rate of the implants was 100%. CONCLUSIONS: Immediately loaded postextractive implants, placed according to the ART, have been proved to be a predictable method to rehabilitate single tooth in the anterior maxilla. PMID- 26836126 TI - Two Composite Bone Graft Substitutes for Maxillary Sinus Floor Augmentation: Histological, Histomorphometric, and Radiographic Analyses. AB - OBJECTIVE: To histologically, histomorphometrically, and radiographically compare clinical performance of 2 composite bone graft substitutes for maxillary sinus floor augmentation (MSFA). MATERIALS AND METHODS: Partially or totally edentulous patients requiring MSFA underwent grafting procedures using a 2:1 mixture of biphasic calcium sulfate (CS) and deproteinized bovine bone (group CB) or biphasic CS and alloplast (group CA). Grafts were allowed to heal for 5 months before placing the implants. During implant surgery, bone samples were collected from grafted areas for histology and histomorphometry. Graft height was analyzed using cone beam computed tomography. RESULTS: Sixteen patients completed the study. Mean percentages of new bone were 34.40% +/- 18.91% and 36.71% +/- 15.32% for the CA and CB groups, respectively; percentages of residual graft particles were 6.98% +/- 5.09% and 5.52% +/- 4.12%, respectively. The only significant finding was a greater graft height loss in the CA group (24.44% +/- 6.52% vs 14.60% +/- 4.58%). CONCLUSION: Both graft substitutes were integrated in bone, confirming their biocompatibility and effectiveness for MSFA. The CB group showed less bone height loss than the CA group. PMID- 26836127 TI - Expression of Pattern Recognition Receptors in Epithelial Cells Around Clinically Healthy Implants and Healthy Teeth. AB - BACKGROUND: Gingival epithelial cells have a pivotal role in the recognition of microorganisms and damage-associated molecular pattern molecules and in the regulation of the immune response. The investigation of the behavior of Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD) like receptors (NLRs) around a healthy implant may help to address the first step of periimplantitis pathogenesis. PURPOSE: To investigate by quantitative real-time polymerase chain reaction, the mRNA expressions of TLR2, TLR3, TLR4, TLR5, TLR6, TLR9, NOD1, NOD2, and NLRP3 from gingival epithelial cells of the sulcus around healthy implants and around healthy teeth. MATERIALS AND METHODS: Two types of implant-abutment systems with tube-in-tube interface were tested. After 6 months of implant restoration, gingival epithelial cells were obtained from the gingival sulcus around the implants and around the adjacent teeth of 10 patients. RESULTS: Our results did not reach statistical significance among the mRNA expressions of TLR2, TLR3, TLR4, TLR5, TLR6, TLR9, NOD1, NOD2, and NLRP3 in epithelial cells around the implant versus around natural teeth. CONCLUSION: This study shows that the implant-abutment systems tested did not induce an immune response by the surrounding epithelial cells at 6 months since their positioning, as well as in the adjacent clincally healthy teeth. PMID- 26836128 TI - Bone Regenerative Potential of Enamel Matrix Protein in the Circumferential Defect Around a Dental Implant. AB - PURPOSE: The aim of this study was to determine the bone regenerative potential of enamel matrix derivative (EMD) in a defect around a dental implant. MATERIALS AND METHODS: Five mongrel dogs were used. A circumferential defect was created around osteotomies that had been fabricated to receive titanium implants. The defects were treated with EMD, biphasic calcium phosphate (BCP), a mixture of EMD and BCP (EBCP), or blood coagulum (control). RESULTS: In general, the amount of new bone formation, the most-coronal level of bone-implant contact, defect fill, and bone-implant contact ratio were greater in the EMD group than in the control group, but the differences did not reach statistical significance. The EBCP group yielded no beneficial effect in new bone formation. Histologically, there was no notable difference in healing pattern between the EMD group and the control, and the EBCP and the BCP group. Few of the specimens in the EMD and EBCP groups exhibited remarkable bone regeneration. CONCLUSIONS: Neither EMD alone nor a mixture of BCP and EMD enhanced bone healing in a circumferential gap defect around a dental implant. PMID- 26836129 TI - Risk Factors in Early Implant Failure: A Meta-Analysis. AB - BACKGROUND: Clinicians should be able to weigh the role of the main risk factors associated with early implant failure. PURPOSE: The aim of this meta-analysis was to assess the influence of different patient-related and implant-related risk factors on the occurrence of early implant failure. MATERIALS AND METHODS: In July, 2014 the main electronic databases were searched for studies reporting on early failures. Relevant papers were selected by 2 independent authors using predefined selection criteria. Three authors independently scored the included studies for quality assessment. The estimated odds ratios of the main risk factors from the selected papers were subjected to meta-analysis. RESULTS: Nine studies were included. A total of 18,171 implants were meta-analyzed, of which 10,921 were analyzed for smoking, 15,260 for implant diameter, 16,075 for implant length, and 16,711 for implant location (maxilla vs mandible). The main significant risk factors for early implant failures were the smoking habit (odds ratio [OR], 1.7; 95% confidence interval [CI], 1.3, 2.3), implants shorter than 10 mm (OR, 1.6; 95% CI, 1.2, 2.2) and implants placed in the maxilla (OR, 1.3; 95% CI, 1.0, 1.6). CONCLUSIONS: Clinicians should be aware of the increased risk of early failure in the presence of smokers, implants with reduced length, and implant-supported maxillary rehabilitation. PMID- 26836130 TI - Chemical Synthesis of Iron Antimonide (FeSb2) and Its Thermoelectric Properties. AB - Low temperature thermoelectric (TE) materials are in demand for more efficient cooling and power generation applications. Iron antimonide (FeSb2) draws great attention over the past few years because of its enhanced power factor values. Polycrystalline bulk FeSb2 nanopowder was prepared via a low-temperature molten salts approach followed by subsequent thermal treatment in synthetic air and hydrogen gas for calcination and reduction reactions, respectively. Structural analysis confirms the desired final phase with submicrometer grain size and high compaction density after consolidation using spark plasma sintering (SPS). TE transport properties revealed that the material is n-type below 150 K and p-type above this temperature; this suggests antimony vacancies in FeSb2. The electrical conductivity increased significantly, and the highest conductivity achieved was 6000 S/cm at 100 K. The maximum figure-of-merit, ZT, of 0.04 is achieved at 500 K, which is about 6 times higher than the earlier reported state-of-the art ZT value for the same material. PMID- 26836131 TI - The Role of Ketamine in Low- and Middle-Income Countries: What Would Happen if Ketamine Becomes a Scheduled Drug? PMID- 26836132 TI - The Goose and the Gander. PMID- 26836133 TI - Ketamine Versus Special K: A Double-Edged Sword. PMID- 26836135 TI - Attenuation of High-Frequency (50-200 Hz) Thalamocortical Electroencephalographic Rhythms by Isoflurane in Rats Is More Pronounced for the Thalamus Than for the Cortex. AB - BACKGROUND: Thalamocortical electroencephalographic rhythms in gamma (30-80 Hz) and high-gamma (80-200 Hz) ranges have been linked to arousal and conscious processes. We have recently shown that propofol causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 50 to 200 Hz range and that this effect is far more pronounced for the thalamus. To determine whether similar attenuation occurs with other anesthetics, we characterized the concentration-effect relationship of the inhaled anesthetic isoflurane on the spectral power of these rhythms. METHODS: Local field potentials were recorded from the barrel cortex and ventroposteromedial thalamic nucleus in 9 chronically instrumented rats to measure spectral power in the gamma/high-gamma range (30-200 Hz). Rats were placed in an airtight chamber and isoflurane was administered at 0.75%, 1.1%, and 1.5% concentrations. Spectral power was assessed during baseline, at the 3 isoflurane concentrations after 30 minutes for equilibration, and during recovery over 4 frequency bands (30-50, 51-75, 76-125, and 126-200 Hz). Unconsciousness was defined as sustained loss of righting reflex. Multiple linear regression was used to model the change in power (after logarithmic transformation) as a function of concentration and recording site. P values were corrected for multiple comparisons. RESULTS: Unconsciousness occurred at the 1.1% concentration in all animals. Isoflurane caused a robust (P <= 0.008) linear concentration-dependent attenuation of cortical and thalamic power in the 30 to 200 Hz range. The concentration-effect slope for the thalamus was steeper than for the cortex in the 51 to 75 Hz (P = 0.029) and 76 to 200 Hz (P < 0.001) ranges but not for the 30 to 50 Hz range (P = 0.320). Comparison with our previously published propofol data showed that slope for cortical power was steeper with isoflurane than with propofol for all frequency bands (P = 0.033). For thalamic power, the slope differences between isoflurane and propofol were not statistically significant (0.087 <= P <= 0.599). CONCLUSIONS: Isoflurane causes a concentration-dependent attenuation of the power of thalamocortical rhythms in the 30 to 200 Hz range, and this effect is more pronounced for the thalamus than for the cortex for frequencies >50 Hz. In comparison with propofol, isoflurane caused a greater attenuation in the cortex, but the effects on the thalamus were similar. Isoflurane and propofol cause common alterations of fast thalamocortical rhythms that may constitute an electrophysiologic signature of the anesthetized state. PMID- 26836134 TI - Advanced Monitoring Is Associated with Fewer Alarm Events During Planned Moderate Procedure-Related Sedation: A 2-Part Pilot Trial. AB - BACKGROUND: Diagnostic and interventional procedures are often facilitated by moderate procedure-related sedation. Many studies support the overall safety of this sedation; however, adverse cardiovascular and respiratory events are reported in up to 70% of these procedures, more frequently in very young, very old, or sicker patients. Monitoring with pulse oximetry may underreport hypoventilation during sedation, particularly if supplemental oxygen is provided. Capnometry may result in false alarms during sedation when patients mouth breathe or displace sampling devices. Advanced monitor use during sedation may allow event detection before complications develop. This 2-part pilot study used advanced monitors during planned moderate sedation to (1) determine incidences of desaturation, low respiratory rate, and deeper than intended sedation alarm events; and (2) determine whether advanced monitor use is associated with fewer alarm events. METHODS: Adult patients undergoing scheduled gastroenterology or interventional radiology procedures with planned moderate sedation given by dedicated sedation nurses under the direction of procedural physicians (procedural sedation team) were monitored per standard protocols (electrocardiography blood pressure, pulse oximetry, and capnometry) and advanced monitors (acoustic respiratory monitoring and processed electroencephalograpy). Data were collected to computers for analysis. Advanced monitor parameters were not visible to teams in part 1 (standard) but were visible to teams in part 2 (advanced). Alarm events were defined as desaturation-SpO2 <=92%; respiratory depression, acoustic respiratory rate <=8 breaths per minute, and deeper than intended sedation, indicated by processed electroencephalograpy. The number of alarm events was compared. RESULTS: Of 100 patients enrolled, 10 were excluded for data collection computer malfunction or consent withdrawal. Data were analyzed from 90 patients (44 standard and 46 advanced). Advanced had fewer total alarms than standard (Wilcoxon-Mann-Whitney = 2.073, P = 0.038; Wilcoxon-Mann Whitney odds, 1.67; 95% confidence interval [CI], 1.04-2.88). Similar numbers of standard and advanced had >=1 alarm event (Wald difference, -10.2%; 95% CI, 26.4% to 7.0%; P = 0.237). Fewer advanced patients had >=1 respiratory depression event (Wald difference, -22.1%; 95% CI, -40.9% to -2.4%; P = 0.036) or >=1 desaturation event (Wald difference, -24.2%; 95% CI, -42.8% to -3.6%; P = 0.021); but there was no significant difference in deeper than intended sedation events (Wald difference, -1.38%; 95% CI, -20.21% to 17.49%; P = 0.887). CONCLUSIONS: Use of advanced monitoring parameters during planned moderate sedation was associated with fewer alarm events, patients experiencing desaturation, and patients experiencing respiratory depression alarm events. This pilot study suggests that further study into the safety and outcome impacts of advanced monitoring during procedure-related sedation is warranted. PMID- 26836136 TI - Fast Versus Slow Recruitment Maneuver at Different Degrees of Acute Lung Inflammation Induced by Experimental Sepsis. AB - BACKGROUND: Large tidal volume (VT) breaths or "recruitment maneuvers" (RMs) are used commonly to open collapsed lungs, but their effectiveness may depend on how the RM is delivered. We hypothesized that a stepped approach to RM delivery ("slow" RM) compared with a nonstepped ("fast" RM), when followed by decremental positive end-expiratory pressure (PEEP) titration to lowest dynamic elastance, would (1) yield a more homogeneous inflation of the lungs, thus reducing the PEEP obtained during post-RM titration; (2) produce less lung morphofunctional injury, regardless of the severity of sepsis-induced acute lung inflammation; and (3) result in less biological damage in severe, but not in moderate, acute lung inflammation. METHODS: Sepsis was induced by cecal ligation and puncture surgery in 51 Wistar rats. After 48 hours, animals were anesthetized, mechanically ventilated (VT = 6 mL/kg), and stratified by PO2/fraction of inspired oxygen ratio into moderate (>=300) and severe (<300) acute lung inflammation groups. Each group was then subdivided randomly into 3 subgroups: (1) nonrecruited; (2) RM with continuous positive airway pressure (30 cm H2O for 30 seconds; CPAPRM or fast RM); and (3) RM with stepwise airway pressure increase (5 cm H2O/step, 8.5 seconds/step, 6 steps, 51 seconds; STEPRM or slow RM), with a maximum pressure hold for 10 seconds. All animals underwent decremental PEEP titration to determine the level of PEEP required to optimize dynamic compliance after RM and were then ventilated for 60 minutes with VT = 6 mL/kg, respiratory rate = 80 bpm, fraction of inspired oxygen = 0.4, and the newly adjusted PEEP for each animal. Respiratory mechanics, hemodynamics, and arterial blood gases were measured before and at the end of 60-minute mechanical ventilation. Lung histology and biological markers of inflammation and damage inflicted to endothelial cells were evaluated at the end of the 60-minute mechanical ventilation. RESULTS: Respiratory system mean airway pressure was lower in STEPRM than that in CPAPRM. The total RM time was greater, and the RM rise angle was lower in STEPRM than that in CPAPRM. In both moderate and severe acute lung inflammation groups, STEPRM reduced total diffuse alveolar damage score compared with the score in nonrecruited rats. In moderate acute lung inflammation, STEPRM rats compared with CPAPRM rats had less endothelial cell damage and angiopoietin (Ang)-2 expression. In severe acute lung inflammation, STEPRM compared with CPAPRM reduced hyperinflation, endothelial cell damage, Ang-2, and intercellular adhesion molecule-1 expressions. RM rise angle correlated with Ang-2 expression. CONCLUSIONS: Compared with CPAPRM, STEPRM reduced biological markers associated with endothelial cell damage and ultrastructural endothelial cell injury in both moderate and severe sepsis-induced acute lung inflammation. PMID- 26836137 TI - Elie Metchnikoff, the Man and the Myth. AB - The year 2016 marks the centenary of the death of Elie Metchnikoff, the father of innate immunity and discoverer of the significance of phagocytosis in development, homeostasis and disease. Through a series of intravital experiments on invertebrates and vertebrates, he described the role of specialised phagocytic cells, macrophages and microphages, subsequently renamed neutrophils and polymorphonuclear leucocytes, in the host response to injury, inflammation, infection and tissue repair. As a vigorous proponent of cellular immunity, he championed its importance versus humoral immunity in the so-called antibody wars. By 1908, when the Nobel Prize was awarded to Elie Metchnikoff and Paul Ehrlich, this debate was not yet resolved. Even earlier, Metchnikoff had turned his research interests to the process of ageing and the possible link to intestinal auto-intoxication, giving rise to the current interest in the microbiome of the gut and the use of probiotics to promote health and longevity. During the past century, Metchnikoff's reputation has waxed and waned, as lymphocyte heterogeneity, specificity and memory began to dominate the field of adaptive immunity, yet his benign visage continues to provide an iconic presence for specialists in innate immunology, whose studies have made a striking comeback in the past decade. In this review, I shall consider the nature of his studies and the person as well as the legendary description of his Eureka experience in Messina in 1882, a story loved by students and investigators alike, that marked, in his own words, his transformation from zoologist to pathologist. PMID- 26836138 TI - The protective effect of blueberry anthocyanins against perfluorooctanoic acid induced disturbance in planarian (Dugesia japonica). AB - The influence of blueberry anthocyanins on perfluorooctanoic acid (PFOA)-induced stress response in planarian mitochondria was investigated. PFOA at 15mg/L and anthocyanins at 10 or 20mg/L were individually and simultaneously administered to planarians for up to 10d. The results showed PFOA treatment induced an increase in mitochondrial permeability transition pore opening and a decrease antioxidant capacity and enzyme activities. In anthocyanin treated animals, the activity of succinate dehydrogenase, cytochrome oxidase and monoamine oxidase increased, but mitochondrial permeability transition pore opening decreased and total antioxidant capacity increased. An improvement in above-mentioned physiological and biochemical parameters was found in the combined PFOA and anthocyanin treated animals, in a dose-dependent manner. Anthocyanins attenuated the PFOA induced toxicity; antioxidant capacity and enzyme activities are involved in the protective mechanism of anthocyanins. PMID- 26836139 TI - Slow synaptic transmission mediated by TRPV1 channels in CA3 interneurons of the hippocampus. AB - Metabotropic glutamate receptors (mGluRs) modulate various neuronal functions in the central nervous system. Many studies reported that mGluRs have linkages to neuronal disorders such as schizophrenia and autism related disorders, indicating that mGluRs are involved in critical functions of the neuronal circuits. To study this possibility further, we recorded mGluR-induced synaptic responses in the interneurons of the CA3 stratum radiatum using rat hippocampal organotypic slice cultures. Electrical stimulation in the CA3 pyramidal cell layer evoked a slow inward current in the interneurons at a holding potential of -70mV in the presence of antagonists for AMPA/kainate receptors, NMDA receptors, GABAA receptors and GABAB receptors. The slow inward current was blocked in the absence of extracellular calcium, suggesting that this was a synaptic response. The slow excitatory postsynaptic current (EPSC) reversed near 0mV, reflecting an increase in a non-selective cationic conductance. The slow EPSC is mediated by group I mGluRs, as it was blocked by AP3, a group I mGluR antagonist. Neither a calcium chelator BAPTA nor a phospholipase C (PLC) inhibitor U73122 affected the slow EPSC. La(3+), a general TRP channel blocker or capsazepine, a selective TRPV1 channel antagonist significantly suppressed the slow EPSC. DHPG, a selective group I mGluRs agonist induced an inward current, which was suppressed by capsazepine. These results indicate that in the interneurons of the hippocampal CA3 stratum radiatum group I mGluRs activate TRPV1 channels independently of PLC and intracellular Ca(2+), resulting in the slow EPSC in the interneurons. PMID- 26836140 TI - The expression of NLRX1 in C57BL/6 mice cochlear hair cells: Possible relation to aging- and neomycin-induced deafness. AB - Nucleotide-binding domain and leucine-rich-repeat-containing family member X1 (NLRX1) is a cytoplasmic pattern recognition receptor that is predominantly located in mitochondria, which is tightly related to mitochondrial damage, reactive oxygen species (ROS) production, inflammation and apoptosis. The present study was designed to explore whether NLRX1 expresses in C57BL/6 mice cochlear hair cells and, if so, to investigate the possible correlations between NLRX1 and hearing. The location and dynamic expression of NLRX1 were investigated by immunofluorescence, real-time PCR and Western blotting. Hearing thresholds of C57BL/6 mice were measured by auditory brainstem response (ABR). Moreover, the downstream inflammatory and apoptotic pathways regulated by NLRX1 were examined in age-related and neomycin-induced hair cell damage. Data showed that NLRX1 expressed in cytoplasm of C57BL/6 cochlear hair cells, especially in the cilia, which were essential for sound sensation. The expression of NLRX1 in hair cells increased as the mice grew up, and, decreased as they aged. Additionally, the activated apoptotic JNK pathway was detected in 9-month old mice with worse hearing and 3-month old mice treated with neomycin. Overall, results indicate that NLRX1 may relate to hair cell maturity, hearing formation and maintenance, and promote hair cell apoptosis through JNK pathway induced by aging and neomycin. PMID- 26836142 TI - Electrophysiology of executive control in spoken noun-phrase production: Dynamics of updating, inhibiting, and shifting. AB - Previous studies have provided evidence that updating, inhibiting, and shifting abilities underlying executive control determine response time (RT) in language production. However, little is known about their electrophysiological basis and dynamics. In the present electroencephalography study, we assessed noun-phrase production using picture description and a picture-word interference paradigm. We measured picture description RTs to assess length, distractor, and switch effects, which have been related to the updating, inhibiting, and shifting abilities. In addition, we measured event-related brain potentials (ERPs). Previous research has suggested that inhibiting and shifting are associated with anterior and posterior N200 subcomponents, respectively, and updating with the P300. We obtained length, distractor, and switch effects in the RTs, and an interaction between length and switch. There was a widely distributed switch effect in the N200, an interaction of length and midline site in the N200, and a length effect in the P300, whereas distractor did not yield any ERP modulation. Moreover, length and switch interacted in the posterior N200. We argue that these results provide electrophysiological evidence that inhibiting and shifting of task set occur before updating in phrase planning. PMID- 26836141 TI - Perinatal thiamine restriction affects central GABA and glutamate concentrations and motor behavior of adult rat offspring. AB - The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life. PMID- 26836143 TI - Specific disgust processing in the left insula: New evidence from direct electrical stimulation. AB - Neuropsychological and neuroimaging studies yielded controversial results concerning the specific role of the insula in recognizing the facial expression of disgust. To verify whether the insula has a selective role in facial disgust processing, emotion recognition was studied in thirteen patients during intraoperative stimulation of the insula in awake surgery performed for removal of a glioma close to this structure. Direct electrical stimulation of the left insula produced a general decrease in emotion recognition but only in the case of disgust there was a statistically significant detrimental effect (p=0.004). Happiness and anger were the best and the worst recognized emotion, respectively. The worst baseline performance with anger and, partly, fear could be explained with the involvement of the left temporal regions, striatum, and the connection between the striatum and the frontal lobe, as suggested in previous studies. Therefore, upon these intra-operative evidences, we argue for a selective role of the left insula in disgust recognition, although a (non significant) decrease in the recognition of other negative emotions was found. However, additional networks can develop, as demonstrated by the fact that disgust recognition was not impaired after surgery even in patients with insular resection in the current as in previous studies. PMID- 26836144 TI - A novel depth-of-interaction block detector for positron emission tomography using a dichotomous orthogonal symmetry decoding concept. AB - Conventionally, a dual-end depth-of-interaction (DOI) block detector readout requires two two-dimensional silicon photomultiplier (SiPM) arrays, one on top and one on the bottom, to define the XYZ positions. However, because both the top and bottom SiPM arrays are reading the same pixels, this creates information redundancy. We propose a dichotomous orthogonal symmetric (DOS) dual-end readout block detector design, which removes this redundancy by reducing the number of SiPMs and still achieves XY and DOI (Z) decoding for positron emission tomography (PET) block detector. Reflecting films are used within the block detector to channel photons going to the top of the block to go only in the X direction, and photons going to the bottom are channeled along the Y direction. Despite the unidirectional channeling on each end, the top readout provides both X and Y information using two one-dimensional SiPM arrays instead of a two-dimensional SiPM array; similarly, the bottom readout also provides both X and Y information with just two one-dimensional SiPM arrays. Thus, a total of four one-dimensional SiPM arrays (4 * N SiPMs) are used to decode the XYZ positions of the firing pixels instead of two two-dimensional SiPM arrays (2 * N * N SiPMs), reducing the number of SiPM arrays per block from 2N(2) to 4 N for PET/MR or PET/CT systems. Moreover, the SiPM arrays on one end can be replaced by two regular photomultiplier tubes (PMTs), so that a block needs only 2 N SiPMs + 2 half PMTs; this hybrid-DOS DOI block detector can be used in PET/CT systems. Monte Carlo simulations were carried out to study the performance of our DOS DOI block detector design, including the XY-decoding quality, energy resolution, and DOI resolution. Both BGO and LSO scintillators were studied. We found that 4 mm pixels were well decoded for 5 * 5 BGO and 9 * 9 LSO arrays with 4 to 5 mm DOI resolution and 16-20% energy resolution. By adding light-channel decoding, we modified the DOS design to a high-resolution design, which resolved scintillator pixels smaller than the SiPM dimensions. Detector pixels of 2.4 mm were decoded for 8 * 8 BGO and 15 * 15 LSO arrays with 5 mm DOI resolution and 20-23% energy resolution. Time performance was also studied for the 8 * 8 BGO and 15 * 15 LSO HR-DOS arrays. The timing resolution for the corner and central crystals is 986 +/- 122 ps and 1.89 +/- 0.17 MUs respectively with BGO, 137 +/- 42 ps and 458 +/- 67 ps respectively with LSO. Monte Carlo simulations with GATE/Geant4 demonstrated the feasibility of our DOS DOI block detector design. In conclusion, our novel design achieved good performance except the time performance while using fewer SiPMs and supporting electronic channels than the current non-DOI PET detectors. This novel design can significantly reduce the cost, heat, and readout complexity of DOI block detectors for PET/MR/CT systems that don't require the time-of-flight capability. PMID- 26836145 TI - Assessing structural and functional responses of murine hearts to acute and sustained beta-adrenergic stimulation in vivo. AB - INTRODUCTION: Given the importance of beta-adrenoceptor signalling in regulating cardiac structure and function, robust protocols are required to assess potential alterations in such regulation in murine models in vivo. METHODS: Echocardiography was performed in naive and stressed (isoprenaline; 30MUg/g/day s.c. for up to 14days) mice, in the absence or presence of acute beta-adrenergic stimulation (dobutamine 0.75MUg/g, i.p.). Controls received saline infusion and/or injection. Hearts were additionally analysed gravimetrically, histologically and biochemically. RESULTS: In naive mice, acute beta-adrenoceptor stimulation with dobutamine increased heart rate, left ventricular (LV) fractional shortening (LVFS), ejection fraction (LVEF) and wall thickness and decreased LV diameter (p<0.05). In stressed mice, dobutamine failed to induce further inotropic and chronotropic responses. Furthermore, following dobutamine injection, these mice exhibited lower LVEF and LVFS at identical heart rates, relative to corresponding controls. Sustained isoprenaline infusion induced LV hypertrophy (increased heart weight, heart weight/body weight ratio, heart weight/tibia length ratio and LV wall thickness (p<0.05)) by 3days, with little further change at 14days. In contrast, increases in LVEF and LVFS were seen only at 14days (p<0.05). DISCUSSION: We describe protocols for and illustrative data from the assessment of murine cardiac responses to acute and sustained beta adrenergic stimulation in vivo, which would be of value in determining the impact of genetic or pharmacological interventions on such responses. Additionally, our data indicate that acute dobutamine stimulation unmasks early signs of LV dysfunction in the remodelled heart, even at a stage when basal function is enhanced. PMID- 26836146 TI - In Crystallo Capture of a Covalent Intermediate in the UDP-Galactopyranose Mutase Reaction. AB - UDP-galactopyranose mutase (UGM) plays an essential role in galactofuranose biosynthesis in pathogens by catalyzing the conversion of UDP-galactopyranose to UDP-galactofuranose. Here we report the first crystal structure of a covalent intermediate in the UGM reaction. The 2.3 A resolution structure reveals UDP bound in the active site and galactopyranose linked to the FAD through a covalent bond between the anomeric C of galactopyranose and N5 of the FAD. The structure confirms the role of the flavin as nucleophile and supports the hypothesis that the proton destined for O5 of galactofuranose is shuttled from N5 of the FAD via O4 of the FAD. PMID- 26836147 TI - Measurement uncertainty for the determination of amphetamines in urine by liquid phase microextraction and gas chromatography-mass spectrometry. AB - A gas chromatography-mass spectrometry method for the determination of amphetamines in urine samples by means of liquid-phase microextraction was validated, including calculation of measurement uncertainty. After extraction in the three-phase mode, acceptor phase was withdrawn from the fiber and the residue was derivatized with trifluoroacetic anhydride. The method showed to be very simple, rapid and it required a significantly low amount of organic solvent for extraction. The limits of detection were 10 and 20MUg/L for amphetamine and methamphetamine, respectively. The calibration curves were linear over the specified range (20MUg/L to 1400MUg/L; r(2)>0.99). The method showed to be both precise and accurate and a relative combined uncertainty of 2% was calculated. In order of importance, the factors which were more determinant for the calculation of method uncertainty were: analyte concentration, sample volume, trueness and method precision. PMID- 26836148 TI - Gender differences in drug abuse in the forensic toxicological approach. AB - Gender differences in substance use/abuse have been the focus of research in the last 15 years. Initiation, use patterns, acceleration of disease course, and help seeking patterns are known to be influenced by gender differences with regard to biological, psychological, cultural and socioeconomic factors. This paper presents a systematic review of published data on gender differences in the use/abuse of psychoactive and psychotic drugs, focusing on the importance of a multidisciplinary approach. The basis for this paper was obtained by Medline searches using the search terms "human" and "gender", combined with individual drug names or "drugs of abuse". The reference lists of these papers were further checked for other relevant studies. The gender difference in drug abuse is more evident in adults than in adolescents (13-19 years): adult men are 2-3 times more likely than women to develop drug abuse/dependence disorders and approximately 4 times as likely to have an alcohol use disorder. Such prevalence rates have not been observed in adolescents. Differences between men and women involve: (i) the biological response to the drug, (ii) the progression to drug dependence, and (iii) the comorbid psychiatric diagnoses, which may be due to both sociocultural factors and innate biological differences. A crucial role played by ovarian hormones (oestrogens and progesterone) has been documented in both human and animal model studies. Epidemiological data on how particular psychobiological and physiological characteristics in females influence vulnerability to both drug addiction and toxicological consequences of drugs are still in their infancy. Significant gaps remain in our knowledge, which are primarily attributable to the lack of empirical data that only a systematic and multidisciplinary approach to the topic can generate. The introduction of gender into forensic toxicological evaluations may help elucidate the relationship between the body's absorption of abused drugs (alone or in combination) and the onset of intoxications, both lethal and none. PMID- 26836149 TI - Synthesis of Cesium Lead Halide Perovskite Nanocrystals in a Droplet-Based Microfluidic Platform: Fast Parametric Space Mapping. AB - Prior to this work, fully inorganic nanocrystals of cesium lead halide perovskite (CsPbX3, X = Br, I, Cl and Cl/Br and Br/I mixed halide systems), exhibiting bright and tunable photoluminescence, have been synthesized using conventional batch (flask-based) reactions. Unfortunately, our understanding of the parameters governing the formation of these nanocrystals is still very limited due to extremely fast reaction kinetics and multiple variables involved in ion metathesis-based synthesis of such multinary halide systems. Herein, we report the use of a droplet-based microfluidic platform for the synthesis of CsPbX3 nanocrystals. The combination of online photoluminescence and absorption measurements and the fast mixing of reagents within such a platform allows the rigorous and rapid mapping of the reaction parameters, including molar ratios of Cs, Pb, and halide precursors, reaction temperatures, and reaction times. This translates into enormous savings in reagent usage and screening times when compared to analogous batch synthetic approaches. The early-stage insight into the mechanism of nucleation of metal halide nanocrystals suggests similarities with multinary metal chalcogenide systems, albeit with much faster reaction kinetics in the case of halides. Furthermore, we show that microfluidics optimized synthesis parameters are also directly transferrable to the conventional flask-based reaction. PMID- 26836150 TI - Looking for Neuroimaging Markers in Frontotemporal Lobar Degeneration Clinical Trials: A Multi-Voxel Pattern Analysis Study in Granulin Disease. AB - In light of future pharmacological interventions, neuroimaging markers able to assess the response to treatment would be crucial. In Granulin (GRN) disease, preclinical data will prompt pharmacological trials in the future. Two main points need to be assessed: (1) to identify target regions in different disease stages and (2) to determine the most accurate functional and structural neuroimaging index to be used. To this aim, we have taken advantage of the multivariate approach of multi-voxel pattern analysis (MVPA) to explore the information of brain activity patterns in a cohort of GRN Thr272fs carriers at different disease stages (14 frontotemporal dementia (FTD) patients and 17 asymptomatic carriers) and a group of 33 healthy controls. We studied structural changes by voxel-based morphometry (VBM), functional connectivity by assessing salience, default mode, fronto-parietal, dorsal attentional, executive networks, and local connectivity by regional homogeneity, amplitude of low frequency fluctuations (ALFF), fractional ALFF (fALFF), degree centrality, and voxel mirrored homotopic connectivity. In FTD patients with GRN mutation, the most predictive measure was VBM structural analysis, while in asymptomatic carriers the best predictor marker was the local connectivity measure (fALFF). Altogether, all indexes demonstrated fronto-temporo-parietal damage in GRN pathology, with widespread structural damage of fronto-parietal and temporal regions when disease is overt. MVPA could be of aid in identifying the most accurate neuroimaging marker for clinical trials. This approach was able to identify both the target region and the best neuroimaging approach, which would be specific in the different disease stages. Further studies are needed to simultaneously integrate multimodal indexes in a classifier able to trace the disease progression moving from preclinical to clinical stage of the disease. PMID- 26836152 TI - Complementary and Alternative Medicine in the Context of Earlier Diagnoses of Alzheimer's Disease: Opening the Conversation to Prepare Ethical Responses. AB - Preclinical Alzheimer's disease (AD), a newly proposed, actively researched, and hotly debated research-only diagnostic category, raises the prospect of an ethical dilemma: whether, and possibly how, to treat a disorder with no target symptoms. This proposed category rests on the detection of a number of biomarkers thought to provide evidence of AD pathophysiology years before any behavioral symptoms manifest. Faced with limited treatment options, patients and their relatives may come to consider complementary and alternative medicine (CAM) a viable option, albeit one with minimal supporting evidence. Accordingly, the hopes and needs of some preclinical patients and their relatives could further fuel market-oriented entrepreneurship for CAM. In this ethics review, we provide background and reflect on some ethical questions related to the roles of key stakeholders arising from the potential for CAM use in the context of a possible preclinical AD diagnosis. PMID- 26836151 TI - Multimodal Magnetic Resonance Imaging in Alzheimer's Disease Patients at Prodromal Stage. AB - One objective of modern neuroimaging is to identify markers that can aid in diagnosis, monitor disease progression, and impact long-term drug analysis. In this study, physiopathological modifications in seven subcortical structures of patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) were characterized by simultaneously measuring quantitative magnetic resonance parameters that are sensitive to complementary tissue characteristics (e.g., volume atrophy, shape changes, microstructural damage, and iron deposition). Fourteen MCI patients and fourteen matched, healthy subjects underwent 3T magnetic resonance imaging with whole-brain, T1-weighted, T2*-weighted, and diffusion-tensor imaging scans. Volume, shape, mean R2*, mean diffusivity (MD), and mean fractional anisotropy (FA) in the thalamus, hippocampus, putamen, amygdala, caudate nucleus, pallidum, and accumbens were compared between MCI patients and healthy subjects. Comparisons were then performed using voxel-based analyses of R2*, MD, FA maps, and voxel-based morphometry to determine which subregions showed the greatest difference for each parameter. With respect to the micro- and macro-structural patterns of damage, our results suggest that different and distinct physiopathological processes are present in the prodromal phase of AD. MCI patients had significant atrophy and microstructural changes within their hippocampi and amygdalae, which are known to be affected in the prodromal stage of AD. This suggests that the amygdala is affected in the same, direct physiopathological process as the hippocampus. Conversely, atrophy alone was observed within the thalamus and putamen, which are not directly involved in AD pathogenesis. This latter result may reflect another mechanism, whereby atrophy is linked to indirect physiopathological processes. PMID- 26836153 TI - Differential Impairment of Cognitive and Affective Mentalizing Abilities in Neurodegenerative Dementias: Evidence from Behavioral Variant of Frontotemporal Dementia, Alzheimer's Disease, and Mild Cognitive Impairment. AB - Cognitive and affective theory of mind (ToM) can be impaired in the course of neurodegenerative dementias. Experimental tests based on different task conditions and/or complexity may fail to capture disease-specific patterns of impairments. In this study, we assessed with a single task both the affective and the cognitive facets of ToM ability in a sample of 47 patients (i.e., 12 AD, 20 bvFTD, and 15 aMCI fulfilling IWG criteria for AD in predementia phase) and 65 healthy controls. Subjects were administered the Story-based Empathy task (SET), a non-verbal task measuring the ability to infer others' intentions (IA) and emotions (EA) compared to a control condition (causal inferences, CI). Global and single sub-condition scores were evaluated with a vectorial method, analyzing the relationship between social abilities and basic cognitive functioning by means of two indices representing the basic ability to perform the task and the balance between basic functions and ToM skills.Dementia (AD and bvFTD) patients showed impaired performances on all SET sub-conditions, whereas aMCI subjects' performance was not different from healthy controls. Vectorial analysis revealed a specific change in the balance between EA and CI conditions only in the bvFTD group, supporting a disproportionate deficit in mental states attribution based on affective cues. The overall deficit in the task in AD appears to be more general and related to the severity of dementia. This latter finding is further supported by the normal performance of the prodromal AD group. PMID- 26836154 TI - Association Between Serum Ceruloplasmin Specific Activity and Risk of Alzheimer's Disease. AB - Meta-analyses demonstrate copper involvement in Alzheimer's disease (AD), and the systemic ceruloplasmin status in relation to copper is an emerging issue. To deepen this matter, we evaluated levels of ceruloplasmin concentration, ceruloplasmin activity, ceruloplasmin specific activity (eCp/iCp), copper, non ceruloplasmin copper iron, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype in a sample of 84 AD patients and 58 healthy volunteers. From the univariate logistic analyses we found that ceruloplasmin concentration, eCp/iCp, copper, transferrin, the ceruloplasmin/transferrin ratio, and the APOE genotype were significantly associated with the probability of AD. In the multivariable logistic regression analysis, we selected the best subset of biological predictors by the forward stepwise procedure. The analysis showed a decrease of the risk of having AD for eCp/iCp (p = 0.001) and an increase of this risk for non-ceruloplasmin copper (p = 0.008), age (p = 0.001), and APOE-E4 allele (p < 0.001). The estimated model showed a good power in discriminating AD patients from healthy controls (area under curve: 88% ; sensitivity: 66% ; specificity 93%). These data strength the breakdown of copper homeostasis and propose eCp/iCp as a reliable marker of ceruloplasmin status. PMID- 26836156 TI - The Online Environment: A Key Variable in the Ethical Response to Complementary and Alternative Medicine for Alzheimer's Disease. AB - Racine et al.'s Ethics Review highlights the challenges associated with the use of complementary and alternative medicine (CAM) in the context of early diagnosis of Alzheimer's disease (AD). As CAM are increasingly promoted and sold on the Internet, the unregulated online environment has the potential to significantly impact the health and well-being of the aging demographic, and in particular of individuals concerned about AD. In this response, the ethical challenges specific to the online environment are discussed and solutions are put forward to empower the aging population to maximize the benefits of the online environment while minimizing the potential harms of misinformation, conflict of interest, and other ethical concerns. PMID- 26836155 TI - Different Expression Patterns of Amyloid-beta Protein Precursor Secretases in Human and Mouse Hippocampal Neurons: A Potential Contribution to Species Differences in Neuronal Susceptibility to Amyloid-beta Pathogenesis. AB - Extensive loss of hippocampal neurons serves a pathological basis for irreversible cognitive impairment in patients with Alzheimer's disease (AD). However, this characteristic cannot be replicated by transgenic mouse models, and its underlying mechanisms are unclear. Here, we present evidence that different expression patterns of amyloid-beta protein precursor (AbetaPP) secretases in human and mouse hippocampal neurons are a decisive cause of species difference in the susceptibility to Abeta pathogenesis. Cell bodies of both pyramidal and granular neurons did not appear to undergo Abeta deposits in the 10-month-old transgenic mutant human AbetaPP/presenilin-1 (PS1) mice. They expressed high levels of non-amyloidogenic alpha-secretase, and its neuroprotective products soluble AbetaPPalpha, but low levels of amyloidogenic beta-secretase and gamma secretase, and a neurotoxic product, Abeta42 peptide. Unlike those found in the mouse, human hippocampal neuronal cell bodies expressed beta-secretase and gamma secretase, but not alpha-secretase, which could increase Abeta generation, thus undergoing death in response to various pathological conditions. Increased hippocampal neuronal apoptosis at 48 h following local microinjection of alpha secretase antibody ADAM10 into the hippocampus of AbetaPP/PS1 mice further suggests that high alpha-secretase expression in mouse neuronal cell bodies is a factor in the paucity of neuronal loss in AD-like pathology. Therefore, selective down-regulation of brain alpha-secretase in transgenic AD models will better replicate the disease spectrum, including decreased brain soluble AbetaPPalpha levels and massive neuronal loss in AD patients, and be beneficial for preclinical therapeutic evaluation of AD. PMID- 26836157 TI - Effect of Continuous Propofol Infusion in Rat on Tau Phosphorylation with or without Temperature Control. AB - Several studies suggest a relationship between anesthesia-induced tau hyperphosphorylation and the development of postoperative cognitive dysfunction. This study further characterized the effects of continuous propofol infusion on tau protein phosphorylation in rats, with or without temperature control. Propofol was administered intravenously to 8-10-week-old male Sprague-Dawley rats and infused to the loss of the righting reflex for 2 h continuously. Proteins from cortex and hippocampus were examined by western blot and immunohistochemistry. Rectal temperature was significantly decreased during propofol infusion. Propofol with hypothermia significantly increased phosphorylation of tau at AT8, AT180, Thr205, and Ser199 in cortex and hippocampus except Ser396. With temperature maintenance, propofol still induced significant elevation of AT8, Thr205, and Ser199 in cortex and hippocampus; however, increase of AT180 and Ser396 was only found in hippocampus and cortex, respectively. Differential effects of propofol with or without hypothermia on multiple tau related kinases, such as Akt/GSK3beta, MAPK pathways, or phosphatase (PP2A), were demonstrated in region-specific manner. These findings indicated that propofol increased tau phosphorylation under both normothermic and hypothermic conditions, and temperature control could partially attenuate the hyperphosphorylation of tau. Further studies are warranted to determine the long term impact of propofol on the tau pathology and cognitive functions. PMID- 26836158 TI - Protective Effect of Amyloid-beta Peptides Against Herpes Simplex Virus-1 Infection in a Neuronal Cell Culture Model. AB - Senile amyloid plaques are one of the main hallmarks of Alzheimer's disease (AD). They correspond to insoluble deposits of amyloid-beta peptides (Abeta) and are responsible for the inflammatory response and neurodegeneration that lead to loss of memory. Recent data suggest that Abeta possess antimicrobial and anti-viral activity in vitro. Here, we have used cocultures of neuroglioma (H4) and glioblastoma (U118-MG) cells as a minimal in vitro model to investigate whether Abeta is produced by neuroglioma cells and whether this could result in protective anti-viral activity against HSV-1 infection. Results showed that H4 cells secreted Abeta42 in response to HSV-1 challenge and that U118-MG cells could rapidly internalize Abeta42. Production of pro-inflammatory cytokines TNFalpha and IL-1beta by H4 and U118-MG cells occurred under basal conditions but infection of the cells with HSV-1 did not significantly upregulate production. Both cell lines produced low levels of IFNalpha. However, extraneous Abeta42 induced strong production of these cytokines. A combination of Abeta42 and HSV-1 induced production of pro-inflammatory cytokines TNFalpha and IL-1beta, and IFNalpha in the cell lines. The reported anti-viral protection of Abeta42 was revealed in transfer experiments involving conditioned medium (CM) of HSV-1 infected H4 cells. CM conferred Abeta-dependent protection against HSV-1 replication in de novo cultures of H4 cells challenged with HSV-1. Type 1 interferons did not play a role in these assays. Our data established that H4 neuroglioma cells produced Abeta42 in response to HSV-1 infection thus inhibiting secondary replication. This mechanism may play a role in the etiology of AD. PMID- 26836159 TI - JNK: A Putative Link Between Insulin Signaling and VGLUT1 in Alzheimer's Disease. AB - In the present work, the involvement of JNK in insulin signaling alterations and its role in glutamatergic deficits in Alzheimer's disease (AD) has been studied. In postmortem cortical tissues, pJNK levels were increased, while insulin signaling and the expression of VGLUT1 were decreased. A significant correlation was found between reduced expression of insulin receptor and VGLUT1. The administration of a JNK inhibitor reversed the decrease in VGLUT1 expression found in a mice model of insulin resistance. It is suggested that activation of JNK in AD inhibits insulin signaling which could lead to a decreased expression of VGLUT1, therefore contributing to the glutamatergic deficit in AD. PMID- 26836160 TI - Predictive Value of Cerebrospinal Fluid Visinin-Like Protein-1 Levels for Alzheimer's Disease Early Detection and Differential Diagnosis in Patients with Mild Cognitive Impairment. AB - Visinin-like protein 1 (VILIP-1) recently emerged as a potential biomarker of Alzheimer's disease (AD). This neuronal calcium sensor protein previously used as a marker of acute ischemic stroke is elevated in the cerebrospinal fluid (CSF) of AD patients. The goal of this study was to assess CSF VILIP-1 potential in early AD diagnosis and in differentiating mild cognitive impairment (MCI) patients with and without risk of AD. Additionally, we tested VILIP-1 ability to differentiate AD from other primary causes of dementia, and predict the progression of AD related cognitive decline. VILIP-1 levels were compared with five CSF AD biomarkers (t-tau, Abeta1-42, p-tau181, p-tau199, and p-tau231). VILIP-1 successfully differentiated two MCI patient groups characterized by absence or presence of pathological levels of these CSF biomarkers, except for t-tau. VILIP 1/Abeta(1-42) and VILIP-1/p-tau181 ratios also differentiated MCI patients with pathological CSF biomarker levels. However, there was no difference in VILIP-1 levels between AD and MCI patients. VILIP-1/Abeta(1-42) and VILIP-1/p-tau231 ratios reached high sensitivities (above 70%) and very high specificities (above 85%) in differentiating AD patients from HC. Additionally, VILIP-1 differentiated AD from patients with Lewy body disease with 77.1% sensitivity and 100% specificity. VILIP-1 potential as a prognostic biomarker of cognitive decline in AD was also proved since VILIP-1/t-tau, VILIP-1/p-tau181, and VILIP-1/p-tau231 ratios correlated with MMSE scores. These data indicate that VILIP-1 alone or in combination with other AD CSF biomarkers represent a valuable marker for the early diagnosis of AD, recognition of MCI patients at higher risk to develop dementia, and in differentiating AD from LBD. PMID- 26836161 TI - Cognitive Stimulation Modulates Platelet Total Phospholipases A2 Activity in Subjects with Mild Cognitive Impairment. AB - We evaluated the effect of cognitive stimulation (CS) on platelet total phospholipases A2 activity (tPLA2A) in patients with mild cognitive impairment (MCI_P). At baseline, tPLA2A negatively correlated with Mini-Mental State Examination score (MMSE_s): patients with MMSE_s <26 (Subgroup 1) had significantly higher activity than those with MMSE_s >=26 (Subgroup 2), who had values similar to the healthy elderly. Regarding CS effect, Subgroup 1 had a significant tPLA2A reduction, whereas Subgroup 2 did not significantly changes after training. Our results showed for the first time that tPLA2A correlates with the cognitive conditions of MCI_P, and that CS acts selectively on subjects with a dysregulated tPLA2A. PMID- 26836162 TI - Memory for Public Events in Mild Cognitive Impairment and Alzheimer's Disease: The Importance of Rehearsal. AB - Ribot's law refers to the better preservation of remote memories compared with recent ones that presumably characterizes retrograde amnesia. Even if Ribot-type temporal gradient has been extensively studied in retrograde amnesia, particularly in Alzheimer's disease (AD), this pattern has not been consistently found. One explanation for these results may be that rehearsal frequency rather than remoteness accounts for the better preservation of these memories. Thus, the aim of present study was to address this question by studying retrograde semantic memory in subjects with amnestic mild cognitive impairment (aMCI) (n = 20), mild AD (n = 20) and in healthy older controls (HC; n = 19). In order to evaluate the impact of repetition as well as the impact of remoteness, we used a test assessing memory for enduring and transient public events that occurred in the recent and remote past. Results show no clear temporal gradient across time periods (1960-1975; 1976-1990; 1991-2005; 2006-2011), but a better performance was observed in all three groups for enduring compared with transient events. Moreover, although deficits were globally found in both patients groups compared with HC, more specific analyses revealed that aMCI patients were only impaired on transient events while AD patients were impaired on both transient and enduring events. Exploratory analyses also revealed a tendency suggesting preservation of remote transient events in aMCI. These findings are discussed with regards to memory consolidation models. PMID- 26836163 TI - Examining the Relationship Between Autobiographical Memory Impairment and Carer Burden in Dementia Syndromes. AB - BACKGROUND: Autobiographical memory (ABM) refers to the capacity to remember one's own past, and is known to be central for supporting one's identity and sense of self. This capacity is commonly affected in Alzheimer's disease (AD), as well as semantic dementia (SD) and behavioral-variant frontotemporal dementia (bvFTD). Importantly, ABM plays a critical social function, facilitating relationship intimacy and empathy, and thus loss of ABM may also negatively affect families and carers. OBJECTIVE: To explore the relationship between ABM disruption and carer burden in AD, SD, and bvFTD, and establish whether characteristic ABM profiles differentially relate to carer burden across dementia syndromes. METHODS: We recruited 12 AD, 10 SD, and 13 bvFTD patients and their primary carer. All participants completed the Autobiographical Interview to assess memory for recent and remote events. Carers completed: the Zarit Burden Interview; Depression, Anxiety and Stress Scale (DASS-21); and the Intimate Bond Measure (IBM). RESULTS: In AD, loss of recent ABM was associated with worse psychological wellbeing of carers on the DASS-21. In contrast in SD, remote ABM dysfunction was associated with SD patients showing greater controlling behavior within their intimate relationships. In bvFTD, surprisingly, despite pervasive ABM impairment, no relationship between extent of ABM loss and carer burden was observed. CONCLUSION: These preliminary results reveal that ABM impairment impacts on patients' families and carers and suggest that these influences vary according to the pattern of ABM dysfunction. Disease-specific interventions focusing on preserved aspects of ABM may improve quality of life for both patients and carers. PMID- 26836164 TI - Predictors of Response to Cholinesterase Inhibitors Treatment of Alzheimer's Disease: Date Mining from the TREDEM Registry. AB - BACKGROUND: The pharmacological treatment of Alzheimer's disease (AD) is based largely on cholinesterase inhibitors (ChEI). OBJECTIVE: To investigate whether or not some non-pharmacological and contextual factors measured prior to starting treatment such as past occupation, lifestyles, marital status, degree of autonomy and cognitive impairment, living alone or with others, and the degree of brain atrophy are associated with a better response to ChEI treatment. METHODS: Eighty four AD and six AD with cerebrovascular disease (AD + CVD) outpatients of Treviso Dementia (TREDEM) Registry, with an average cholinesterase inhibitors treatment length of four years, were considered. The outpatients had undergone a complete evaluation and some non-pharmacological and contextual factors were collected. We defined responder a patient with a delta score T0 - T1 equal or inferior to 2.0 points per year of MMSE and a non-responder a patient with a delta score T0 - T1 superior to 2.0 points per year. In order to identify hidden relationships between variables related to response and non-response, we use a special kind of artificial neural network called Auto-CM, able to create a semantic connectivity map of the variables considered in the study. RESULTS: A higher cognitive profile, a previous intellectual occupation, healthier lifestyles, being married and not living alone, a higher degree of autonomy, and lower degree of brain atrophy at baseline resulted in affecting the response to long-term ChEI therapy. CONCLUSION: Non-pharmacological and contextual factors appear to influence the effectiveness of treatment with ChEI in the long term. PMID- 26836166 TI - Discovering New Genes in the Pathways of Common Sporadic Neurodegenerative Diseases: A Bioinformatics Approach. AB - Late onset Alzheimer's disease (AD) and Parkinson's disease (PD) are mostly "sporadic" age-related neurodegenerative disorders, but with a clear genetic component. However, their genetic architecture is complex and heterogeneous, largely remaining a conundrum, with only a handful of well-established genetic risk factors consistently associated with these diseases. It is possible that numerous, yet undiscovered, AD and PD related genes might exist. We focused on the 'gene' as a mediator to find new potential genes that might have a relationship with both disorders using bio-literature mining techniques. Based on Entrez Gene, we extracted the genes and directional gene-gene relation in the entire MEDLINE records and then constructed a directional gene-gene network. We identified common genes associated with two different but related diseases by performing shortest path analysis on the network. With our approach, we were able to identify and map already known genes that have a direct relationship with PD and AD. In addition, we identified 7 genes previously unknown to be a bridge between these two disorders. We confirmed 4 genes, ROS1, FMN1, ATP8A2, and SNORD12C, by biomedical literature and further checked 3 genes, ERVK-10, PRS, and C7orf49, that might have a high possibility to be related with both diseases. Additional experiments were performed to demonstrate the effectiveness of our proposed method. Comparing to the co-occurrence approach, our approach detected 25% more candidate genes and verified 10% more genes that have the relationship between both diseases than the co-occurrence approach did. PMID- 26836165 TI - Modulation of miR-19 in Aluminum-Induced Neural Cell Apoptosis. AB - Neuronal cell death is an important feature of neurodegeneration. Aluminum is associated with neurodegenerative disorders, particularly Alzheimer's disease. However, the underlying mechanisms by which aluminum induces neuronal apoptosis remain to be elucidated. miR-19 is a key miRNA implicated in regulating cell survival process, while the role of miR-19 in Alzheimer's disease has not been investigated. In the present study, we showed that Aluminum maltolate (Al-malt), a lipophilic Al complex which is a common component of human diet with the ability to facilitate the entry of Al into the brain, induced apoptosis in human neuroblastoma SH-SY5Y cells, along with downregulation of miR-19a/miR-19b, upregulation of miR-19-targeted PTEN, and alterations of its downstream apoptosis related proteins including AKT, p53, Bax, and Bcl-2. miR-19 overexpression attenuated Al-malt-induced apoptosis as well as changes in the expression of apoptosis related proteins in SH-SY5Y cells. We further revealed that exposure of rats to Al-malt for 12 weeks at doses relevant to human exposure significantly elevated Al concentrations in serum and brain tissues. Al-malt dose-dependently induced apoptosis in rat brain, as evidenced by increased caspase activation and increased TUNEL staining. Consistent with in vitro results, Al-malt reduced miR 19 expression and altered the expression of apoptotic related proteins in rat brain. Taken together, our data suggest for the first time that miR-19 modulation is critically involved in Al-induced neural cell apoptosis. Findings from this study could provide new insight into the molecular mechanisms of Al-associated neurodegenerative pathogenesis. PMID- 26836167 TI - Psychometric Properties of the Memory Binding Test: Test-Retest Reliability and Convergent Validity. AB - BACKGROUND: Episodic memory testing is fundamental for the diagnosis of Alzheimer's disease (AD). Although the Free and Cued Selective Reminding Test (FCSRT) is widely used for this purpose, it may not be sensitive enough for early detection of subtle decline in preclinical AD. The Memory Binding Test (MBT) intends to overcome this limitation. OBJECTIVES: To analyze the test-retest reliability of the MBT and its convergent validity with the FCRST. METHODS: 36 cognitively healthy participants of the ALFA Study, aged 45 to 65, were included for the test-retest study and 69 for the convergent analysis. They were visited twice in a period of 6 +/- 2 weeks. Test-retest reliability was determined by the calculation of the intra-class correlation coefficient (ICC). Score differences were studied by computing the mean percentage of score variation between visits and visualized by Bland-Altman plots. Convergent validity was determined by Pearson's correlations. RESULTS: ICC values in the test-retest reliability analysis of the MBT direct scores ranged from 0.64 to 0.76. Subjects showed consistent practice effects, with mean amounts of score increasing between 10% and 26%. Pearson correlation between MBT and FCSRT direct scores showed r values between 0.40 and 0.53. The FCSRT displayed ceiling effects not observed in the MBT. CONCLUSIONS: The MBT shows adequate test-retest reliability and overall moderate convergent validity with the FCSRT. Unlike the FCSRT, the MBT does not have ceiling effects and it may therefore be especially useful in longitudinal studies, facilitating the measurement of subtle memory performance decline and the detection of very early AD. PMID- 26836168 TI - Analysis of the MIRIAD Data Shows Sex Differences in Hippocampal Atrophy Progression. AB - BACKGROUND: Hippocampus (HC) atrophy is a hallmark of early Alzheimer's disease (AD). Atrophy rates can be measured by high-resolution structural MRI. Longitudinal studies have previously shown sex differences in the progression of functional and cognitive deficits and rates of brain atrophy in early AD dementia. It is important to corroborate these findings on independent datasets. OBJECTIVE: To study temporal rates of HC atrophy over a one-year period in probable AD patients and cognitively normal (CN) subjects by longitudinal MRI scans obtained from the Minimal Interval Resonance Imaging in AD (MIRIAD) database. METHODS: We used a novel algorithm to compute an index of hippocampal (volumetric) integrity (HI) at baseline and one-year follow-up in 43 mild moderate probable AD patients and 22 CN subjects in MIRIAD. The diagnostic power of longitudinal HI measurement was assessed using a support vector machines (SVM) classifier. RESULTS: The HI was significantly reduced in the AD group (p < 10( 20)). In addition, the annualized percentage rate of reduction in HI was significantly greater in the AD group (p < 10(-13)). Within the AD group, the annual reduction of HI in women was significantly greater than in men (p = 0.008). The accuracy of SVM classification between AD and CN subjects was estimated to be 97% by 10-fold cross-validation. CONCLUSION: In the MIRIAD patients with probable AD, the HC atrophies at a significantly faster rate in women as compared to men. Female sex is a risk factor for faster descent into AD. The HI measure has potential for AD diagnosis, as a biomarker of AD progression and a therapeutic target in clinical trials. PMID- 26836169 TI - Reversible Mild Cognitive Impairment: The Role of Comorbidities at Baseline Evaluation. AB - The prognostic value of mild cognitive impairment (MCI) is being questioned, with some MCI subjects reverting to normal cognition (NC). The reversion rate varies mostly depending on the study design, the setting, and both MCI and NC definitions. Previous studies have focused on the profile of subjects who revert to NC, but the role of comorbidities has not been entirely investigated. We aimed to evaluate the proportion of MCI subjects who revert to NC in a memory clinic context, focusing on the role of comorbidities. Between 2004 and 2013, 374 MCI subjects were recruited. During a mean time of 32 +/- 25.5 months, 21 subjects (5.6%) reverted to NC. Subjects who reverted to NC were younger (p = 0.0001), more educated (p = 0.0001), had a better global cognition (p = 0.0001), as assessed by the Mini-Mental State Examination (MMSE) and suffered from more comorbidities (p = 0.002), as assessed by Cumulative Illness Rating Scale (CIRS) than those who developed dementia. The Cox Regression Model, constructed to adjust for the confounders, showed that the higher were the MMSE (HR = 1.83, CI 95%: 1.07-3.11) and the CIRS score (HR = 1.3, CI 95% 0.88-1.92) at baseline, the higher was the probability of returning to NC than developing dementia, though the last association was not significant. Subjects who reverted to NC were more frequently affected by respiratory (p = 0.002), urologic (p = 0.012), and psychiatric (p = 0.012) diseases. The cognitive performance of subjects with medical comorbidities could benefit from preventive strategies aimed at treating the underlying diseases. PMID- 26836170 TI - The Effects of Latrepirdine on Amyloid-beta Aggregation and Toxicity. AB - Latrepirdine (Dimebon) has been demonstrated to be a neuroprotective and cognition improving agent in neurodegenerative diseases that feature protein aggregation and deposition, such as Alzheimer's disease (AD). The accumulation of amyloid-beta (Abeta) protein aggregates is a key event in the neurodegenerative process in AD. This study explores if latrepirdine modulation of protein aggregation contributes to its neuroprotective mechanism of action. Assessment of neuronal cell death showed that there was a significant reduction in lactate dehydrogenase release at an equimolar ratio of Abeta:latrepirdine and with lower concentrations of latrepirdine. The ability of latrepirdine to alter the formation of Abeta42 aggregates was assessed by thioflavin-T fluorescence, western immunoblotting and atomic force microscopy (AFM). Despite showing a reduction in thioflavin-T fluorescence with latrepirdine treatment, indicating a decrease in aggregation, immunoblotting and AFM showed a modest increase in both the formation and size of Abeta aggregates. The discrepancies between thioflavin T and the other assays are consistent with previous evidence that cyclic molecules can interfere with thioflavin-T binding of amyloid protein preparations. The ability of latrepirdine to modulate Abeta aggregation appears to be independent of its neuroprotective effects, and is unlikely to be a mechanism by which latrepirdine offers protection. This study investigates the effect of latrepirdine on Abeta aggregation, and presents evidence suggesting that caution should be applied in the use of thioflavin-T fluorescence based assays as a method for screening compounds for protein aggregation altering properties. PMID- 26836172 TI - "I Don't Think Of It As An Illness": Illness Representations in Mild to Moderate Dementia. AB - The self-regulatory model proposes that illness representations influence adjustment and coping in chronic conditions. Better understanding of the illness representations held by people with dementia could help with targeting information and support so as to optimize adjustment and coping. In this mixed methods study of illness representations among people with mild to moderate Alzheimer's, vascular, or mixed dementia we aimed to clarify the nature of the representations held, to determine whether specific profiles can be identified based on perceptions of the identity and cause of the condition, and to examine associations between these profiles and other participant characteristics. Data were collected in the second wave of the Memory Impairment and Dementia Awareness Study (MIDAS). Sixty-four people with dementia, who had been told their diagnosis at a memory clinic, completed interviews and responded to questionnaires. In each case a carer was also interviewed. Cluster analysis based on responses about identity and cause identified three profiles. 'Illness' cluster participants saw themselves as living with an illness and used diagnostic labels, 'ageing' cluster participants did not use diagnostic labels and viewed their difficulties as related to ageing, and 'no problem' cluster participants considered that they did not have any difficulties. 'Illness' cluster participants had better cognition and better awareness, but lower mood, and perceived more practical consequences, than 'ageing' cluster participants. Holding an 'illness' model may not be advantageous. Rather than encouraging adoption of such a model, it may be preferable to target information and select interventions in line with the person's representation profile. PMID- 26836171 TI - Measuring Information Processing Speed in Mild Cognitive Impairment: Clinical Versus Research Dichotomy. AB - A substantial body of research evidence is indicative of disproportionately slowed information processing speed in a wide range of multi-trial, computer based, neuroimaging- and electroencephalography-based reaction time (RT) tests in Alzheimer's disease and mild cognitive impairment (MCI). However, in what is arguably a dichotomy between research evidence and clinical practice, RT associated with different brain functions is rarely assessed as part of their diagnosis. Indeed, often only the time taken to perform a single, specific task, commonly the Trail making test (TMT), is measured. In clinical practice therefore, there can be a failure to assess adequately the integrity of the rapid, serial information processing and response, necessary for efficient, appropriate, and safe interaction with the environment. We examined whether a typical research-based RT task could at least match the TMT in differentiating amnestic MCI (aMCI) from cognitively healthy aging at group level. As aMCI is a heterogeneous group, typically containing only a proportion of individuals for whom aMCI represents the early stages of dementia, we examined the ability of each test to provide intra-group performance variation. The results indicate that as well as significant slowing in performance of the operations involved in TMT part B (but not part A), individuals with aMCI also experience significant slowing in RT compared to controls. The results also suggest that research typical RT tests may be superior to the TMT in differentiating between cognitively healthy aging and aMCI at group level and in revealing the performance variability one would expect from an etiologically heterogeneous disorder such as aMCI. PMID- 26836173 TI - Normal Amplitude of Electroretinography and Visual Evoked Potential Responses in AbetaPP/PS1 Mice. AB - Alzheimer's disease has been shown to affect vision in human patients and animal models. This may pose the risk of bias in behavior studies and therefore requires comprehensive investigation. We recorded electroretinography (ERG) under isoflurane anesthesia and visual evoked potentials (VEP) in awake amyloid expressing AbetaPPswe/PS1dE9 (AbetaPP/PS1) and wild-type littermate mice at a symptomatic age. The VEPs in response to patterned stimuli were normal in AbetaPP/PS1 mice. They also showed normal ERG amplitude but slightly shortened ERG latency in dark-adapted conditions. Our results indicate subtle changes in visual processing in aged male AbetaPP/PS1 mice specifically at a retinal level. PMID- 26836175 TI - Increased Intrinsic Activity of Medial-Temporal Lobe Subregions is Associated with Decreased Cortical Thickness of Medial-Parietal Areas in Patients with Alzheimer's Disease Dementia. AB - In Alzheimer's disease (AD), disrupted connectivity between medial-parietal cortices and medial-temporal lobes (MTL) is linked with increased MTL local functional connectivity, and parietal atrophy is associated with increased MTL memory activation. We hypothesized that intrinsic activity in MTL subregions is increased and associated with medial-parietal degeneration and impaired memory in AD. To test this hypothesis, resting-state-functional and structural-MRI was assessed in 22 healthy controls, 22 mild cognitive impairment patients, and 21 AD dementia patients. Intrinsic activity was measured by power-spectrum density of blood-oxygenation-level-dependent signal, medial-parietal degeneration by cortical thinning. In AD-dementia patients, intrinsic activity was increased for several right MTL subregions. Raised intrinsic activity in dentate gyrus and cornu ammonis 1 was associated with cortical thinning in posterior cingulate cortices, and at-trend with impaired delayed recall. Critically, increased intrinsic activity in the right entorhinal cortex was associated with ipsilateral posterior cingulate degeneration. Our results provide evidence that in AD, intrinsic activity in MTL subregions is increased and associated with medial parietal atrophy. Results fit a model in which medial-parietal degeneration contributes to MTL dysconnectivity from medial-parietal cortices, potentially underpinning disinhibition-like changes in MTL activity. PMID- 26836176 TI - Application of the IWG-2 Diagnostic Criteria for Alzheimer's Disease to the ADNI. AB - BACKGROUND: The International Working Group (IWG) recently proposed the revised diagnostic criteria for Alzheimer's disease (AD) to define and refine several types of AD, and to reclassify AD-related biomarkers into diagnostic and progression markers, but its performance is not known. OBJECTIVE: This study was designed to describe the application of the revised IWG criteria in the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and to ascertain whether diagnostic and progression markers show significant differences in their relationships to AD severity and progression. METHODS: Based on the requirements of the refined criteria, 857 ADNI subjects with memory evaluation and at least one pathophysiological marker (CSF or amyloid imaging biomarkers) were eligible and reclassified in this study, and we calculated the associations of diagnostic (CSF and amyloid PET) and progression markers (MRI and fluorodeoxyglucose-PET) with AD severity and progression respectively. RESULTS: The majority (84.2% ) of ADNI AD group (n = 117) and 173 MCI (37.4% ) subjects in ADNI met the definition of typical AD; and 105 cognitively normal (41.0% ) individuals were diagnosed as asymptomatic AD. Furthermore, diagnostic and progression markers showed significant differences when correlated to AD severity and progression. CONCLUSION: A large proportion of AD dementia subjects were categorized as typical AD, and the revised criteria could identify typical AD from MCI status as well as asymptomatic AD at the asymptomatic stage. Moreover, the significant differences between diagnostic and progression markers further supported the new biomarkers categorization in the refined criteria. PMID- 26836177 TI - Prevention Trials in Alzheimer's Disease: Current Status and Future Perspectives. AB - Alzheimer's disease (AD) is the most common form of dementia in the elderly. Over the past 20 years, both pharmacological and lifestyle interventions have been studied for AD prevention, but the overall results have been disappointing. The majority of disappointing results have raised questions and great challenges for the future of AD prevention trials. Ongoing advances in the knowledge of pathogenesis, in the identification of novel targets, in improved outcome measures, and in identification and validation of biomarkers may lead to effective strategies for AD prevention. In this paper, we review the selection of participants and interventions, trial design, outcome assessments, and promising biomarkers in prevention trials, and summarize the lessons learned from completed trials and perspectives from ongoing trials in AD prevention. Selection of optimal participants and interventions, coupled with more refined outcomes and more efficient trial design, may have the capacity to deliver a new era of preventive discovery in this challenging area. PMID- 26836178 TI - Effects of Hypertension and Anti-Hypertensive Treatment on Amyloid-beta (Abeta) Plaque Load and Abeta-Synthesizing and Abeta-Degrading Enzymes in Frontal Cortex. AB - Epidemiological data associate hypertension with a predisposition to Alzheimer's disease (AD), and a number of postmortem and in vivo studies also demonstrate that hypertension increases amyloid-beta (Abeta) pathology. In contrast, anti hypertensive medications reportedly improve cognition and decrease the risk of AD, while certain classes of anti-hypertensive drugs are associated with decreased AD-related pathology. We investigated the effects of hypertension and anti-hypertensive treatment on Abeta plaque load in postmortem frontal cortex in AD. Abeta load was significantly increased in hypertensive (n = 20) relative to normotensive cases (n = 62) and was also significantly higher in treated (n = 9) than untreated hypertensives (n = 11). We then looked into mechanisms by which hypertension and treatment might increase Abeta load, focusing on Abeta synthesizing enzymes, beta- and gamma-secretase, and Abeta-degrading enzymes, angiotensin-converting enzyme (ACE), insulin-degrading enzyme (IDE) and neprilysin. ACE and IDE protein levels were significantly lower in hypertensive (n = 21) than normotensive cases (n = 64), perhaps translating to decreased Abeta catabolism in hypertensives. ACE level was significantly higher in treated (n = 9) than untreated hypertensives (n = 12), possibly reflecting feedback upregulation of the renin-angiotensin system. Prospective studies in larger cohorts stratified according to anti-hypertensive drug class are needed to confirm these initial findings and to elucidate the interactions between hypertension, anti-hypertensive treatments, and Abeta metabolism. PMID- 26836174 TI - Vitamin D and Memory Decline: Two Population-Based Prospective Studies. AB - BACKGROUND: Vitamin D deficiency has been linked with dementia risk, cognitive decline, and executive dysfunction. However, the association with memory remains largely unknown. OBJECTIVE: To investigate whether low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with memory decline. METHODS: We used data on 1,291 participants from the US Cardiovascular Health Study (CHS) and 915 participants from the Dutch Longitudinal Aging Study Amsterdam (LASA) who were dementia-free at baseline, had valid vitamin D measurements, and follow-up memory assessments. The Benton Visual Retention Test (in the CHS) and Rey's Auditory Verbal Learning Test (in the LASA) were used to assess visual and verbal memory, respectively. RESULTS: In the CHS, those moderately and severely deficient in serum 25(OH)D changed -0.03 SD (95% CI: -0.06 to 0.01) and -0.10 SD (95% CI: 0.19 to -0.02) per year respectively in visual memory compared to those sufficient (p = 0.02). In the LASA, moderate and severe deficiency in serum 25(OH)D was associated with a mean change of 0.01 SD (95% CI: -0.01 to 0.02) and 0.01 SD (95% CI: -0.04 to 0.02) per year respectively in verbal memory compared to sufficiency (p = 0.34). CONCLUSIONS: Our findings suggest an association between severe vitamin D deficiency and visual memory decline but no association with verbal memory decline. They warrant further investigation in prospective studies assessing different memory subtypes. PMID- 26836179 TI - Tract-Specific Correlates of Neuropsychological Deficits in Patients with Subcortical Vascular Cognitive Impairment. AB - The white matter tract-specific correlates of neuropsychological deficits are not fully established in patients with subcortical vascular cognitive impairment (SVCI), where white matter tract damage may be a critical factor in cognitive impairment. The purpose of this study is to investigate the tract-specific correlates of neuropsychological deficits in SVCI patients using tract-specific statistical analysis (TSSA). We prospectively recruited 114 SVCI patients, and 55 age-, gender-, and education-matched individuals with normal cognition (NC). All participants underwent diffusion weighted imaging and neuropsychological testing. We classified tractography results into fourteen major fiber tracts and analyzed group comparison and correlation with cognitive impairments. Relative to NC subjects, SVCI patients showed decreased fractional anisotropy values in bilateral anterior-thalamic radiation, cingulum, superior-longitudinal fasciculus, uncinate fasciculus, corticospinal tract, and left inferior longitudinal fasciculus. Focal disruptions in specific tracts were associated with specific cognitive impairments. Our findings suggest that disconnection of specific white matter tracts, especially those neighboring and providing connections between gray matter regions important to certain cognitive functions, may contribute to specific cognitive impairments in SVCI. PMID- 26836180 TI - Post Hoc Analyses of ApoE Genotype-Defined Subgroups in Clinical Trials. AB - BACKGROUND: Many post hoc analyses of clinical trials in Alzheimer's disease (AD) and mild cognitive impairment (MCI) are in small Phase 2 trials. Subject heterogeneity may lead to statistically significant post hoc results that cannot be replicated in larger follow-up studies. OBJECTIVE: We investigated the extent of this problem using simulation studies mimicking current trial methods with post hoc analyses based on ApoE4 carrier status. METHODS: We used a meta-database of 24 studies, including 3,574 subjects with mild AD and 1,171 subjects with MCI/prodromal AD, to simulate clinical trial scenarios. Post hoc analyses examined if rates of progression on the Alzheimer's Disease Assessment Scale cognitive (ADAS-cog) differed between ApoE4 carriers and non-carriers. RESULTS: Across studies, ApoE4 carriers were younger and had lower baseline scores, greater rates of progression, and greater variability on the ADAS-cog. Up to 18% of post hoc analyses for 18-month trials in AD showed greater rates of progression for ApoE4 non-carriers that were statistically significant but unlikely to be confirmed in follow-up studies. The frequency of erroneous conclusions dropped below 3% with trials of 100 subjects per arm. In MCI, rates of statistically significant differences with greater progression in ApoE4 non carriers remained below 3% unless sample sizes were below 25 subjects per arm. CONCLUSIONS: Statistically significant differences for ApoE4 in post hoc analyses often reflect heterogeneity among small samples rather than true differential effect among ApoE4 subtypes. Such analyses must be viewed cautiously. ApoE genotype should be incorporated into the design stage to minimize erroneous conclusions. PMID- 26836181 TI - Classification of Neuropsychiatric Symptoms Requiring Antipsychotic Treatment in Patients with Alzheimer's Disease: Analysis of the CATIE-AD Study. AB - BACKGROUND: The Neuropsychiatric Inventory (NPI) comprises 12 items, which were conventionally determined by psychopathological symptoms of patients with dementia. The clinical rating scales with structured questionnaires have been useful to evaluate neuropsychiatric symptoms (NPSs) of patients with dementia over the past twenty year. OBJECTIVE: The aim of this study was to classify the conventional NPSs in patients with Alzheimer's disease (AD) requiring antipsychotic treatment for their NPSs into distinct clusters to simplify assessment of these numerous symptoms. METHODS: Twelve items scores (product of severity and frequency of each symptom) in the NPI taken from the baseline visit were classified into subgroups by principle component analysis using data from 421 outpatients with AD enrolled in the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Phase 1. Chi square tests were conducted to examine the co-occurrence of the subgroups. RESULTS: We found four distinct clusters: aggressiveness (agitation and irritabilities), apathy and eating problems (apathy and appetite/eating disturbance), psychosis (delusions and hallucinations), and emotion and disinhibition (depression, euphoria, and disinhibition). Anxiety, aberrant motor behavior, and sleep disturbance were not included by these clusters. Apathy and eating problems, and emotion and disinhibition co-occurred (p = 0.002), whereas aggressiveness and psychosis occurred independent of the other clusters. CONCLUSIONS: Four distinct category clusters were identified from NPSs in patients with AD requiring antipsychotic treatment. Future studies should investigate psychosocial backgrounds or risk factors of each distinct cluster, in addition to their longitudinal course over treatment intervention. PMID- 26836184 TI - Naphthoquinone-Tryptophan Hybrid Inhibits Aggregation of the Tau-Derived Peptide PHF6 and Reduces Neurotoxicity. AB - Tauopathies, such as Alzheimer's disease (AD), are a group of disorders characterized neuropathologically by intracellular toxic accumulations of abnormal protein aggregates formed by misfolding of the microtubule-associated protein tau. Since protein self-assembly appears to be an initial key step in the pathology of this group of diseases, intervening in this process can be both a prophylactic measure and a means for modifying the course of the disease for therapeutic purposes. We and others have shown that aromatic small molecules can be effective inhibitors of aggregation of various protein assemblies, by binding to the aromatic core in aggregation-prone motifs and preventing their self assembly. Specifically, we have designed a series of small aromatic naphthoquinone-tryptophan hybrid molecules as candidate aggregation inhibitors of beta -sheet based assembly and demonstrated their efficacy toward inhibiting aggregation of the amyloid-beta peptide, another culprit of AD, as well as of various other aggregative proteins involved in other protein misfolding diseases. Here we tested whether a leading naphthoquinone-tryptophan hybrid molecule, namely NQTrp, can be repurposed as an inhibitor of the aggregation of the tau protein in vitro and in vivo. We show that the molecule inhibits the in vitro assembly of PHF6, the aggregation-prone fragment of tau protein, reduces hyperphosphorylated tau deposits and ameliorates tauopathy-related behavioral defect in an established transgenic Drosophila model expressing human tau. We suggest that NQTrp, or optimized versions of it, could act as novel disease modifying drugs for AD and other tauopathies. PMID- 26836182 TI - Cerebrospinal Fluid Markers of Alzheimer's Disease Pathology and Microglial Activation are Associated with Altered White Matter Microstructure in Asymptomatic Adults at Risk for Alzheimer's Disease. AB - BACKGROUND: The immune response in Alzheimer's disease (AD) involves activation of microglia which may remove amyloid-beta (Abeta). However, overproduction of inflammatory compounds may exacerbate neural damage in AD. AD pathology accumulates years before diagnosis, yet the extent to which neuroinflammation is involved in the earliest disease stages is unknown. OBJECTIVE: To determine whether neuroinflammation exacerbates neural damage in preclinical AD. METHODS: We utilized cerebrospinal fluid (CSF) and magnetic resonance imaging collected in 192 asymptomatic late-middle-aged adults (mean age = 60.98 years). Neuroinflammatory markers chitinase-3-like protein 1 (YKL-40) and monocyte chemoattractant protein-1 (MCP-1) in CSF were utilized as markers of neuroinflammation. Neural cell damage was assessed using CSF neurofilament light chain protein (NFL), CSF total tau (T-Tau), and neural microstructure assessed with diffusion tensor imaging (DTI). With regard to AD pathology, CSF Abeta42 and tau phosphorylated at threonine 181 (P-Tau181) were used as markers of amyloid and tau pathology, respectively. We hypothesized that higher YKL-40 and MCP-1 in the presence of AD pathology would be associated with higher NFL, T-Tau, and altered microstructure on DTI. RESULTS: Neuroinflammation was associated with markers of neural damage. Higher CSF YKL-40 was associated with both higher CSF NFL and T-Tau. Inflammation interacted with AD pathology, such that greater MCP-1 and lower Abeta42 was associated with altered microstructure in bilateral frontal and right temporal lobe and that greater MCP-1 and greater P-Tau181 was associated with altered microstructure in precuneus. CONCLUSION: Inflammation may play a role in neural damage in preclinical AD. PMID- 26836185 TI - Differential Regulation of N-Methyl-D-Aspartate Receptor Subunits is an Early Event in the Actions of Soluble Amyloid-beta(1-40) Oligomers on Hippocampal Neurons. AB - Synaptic dysfunction during early stages of Alzheimer's disease (AD) is triggered by soluble amyloid-beta (Abeta) oligomers that interact with NMDA receptors (NMDARs). We previously showed that Abeta induces synaptic protein loss through NMDARs, albeit through undefined mechanisms. Accordingly, we here examined the contribution of individual NMDAR subunits to synaptotoxicity and demonstrate that Abeta exerts differential effects on the levels and distribution of GluN2A and GluN2B subunits of NMDAR in dendrites. Treatment of cultured hippocampal neurons with Abeta1-40 (10 MUM, 1 h) induced a significant increase of dendritic and synaptic GluN2B puncta densities with parallel decreases in the puncta densities of denritic and synaptic pTyr1472-GluN2B. Conversely, Abeta significantly decreased dendritic and synaptic GluN2A and dendritic pTyr1325-GluN2A puncta densities and increased synaptic pTyr1325-GluN2A puncta densities. Unexpectedly, Abeta treatment resulted in a significant reduction of GluN2B and pTyr1472-GluN2B protein levels but did not influence GluN2A and pTyr1325-GluN2A levels. These results show that Abeta exerts complex and distinct regulatory effects on the trafficking and phosphorylation of GluN2A and GluN2B, as well as on their localization within synaptic and non-synaptic sites. Increased understanding of these early events in Abeta-induced synaptic dysfunction is likely to be important for the development of timely preventive and therapeutic interventions. PMID- 26836183 TI - Cigarette Smoke-Induced Alterations in Frontal White Matter Lipid Profiles Demonstrated by MALDI-Imaging Mass Spectrometry: Relevance to Alzheimer's Disease. AB - BACKGROUND: Meta-analysis has shown that smokers have significantly increased risks for Alzheimer's disease (AD), and neuroimaging studies showed that smoking alters white matter (WM) structural integrity. OBJECTIVE: Herein, we characterize the effects of cigarette smoke (CS) exposures and withdrawal on WM myelin lipid composition using matrix assisted laser desorption and ionization-imaging mass spectrometry (MALDI-IMS). METHODS: Young adult male A/J mice were exposed to air (8 weeks; A8), CS (4 or 8 weeks; CS4, CS8), or CS8 followed by 2 weeks recovery (CS8 + R). Frontal lobe WM was examined for indices of lipid and protein oxidation and lipid profile alterations by MALDI-IMS. Lipid ions were identified by MS/MS with the LIPID MAPS prediction tools database. Inter-group comparisons were made using principal component analysis and R-generated heatmap. RESULTS: CS increased lipid and protein adducts such that higher levels were present in CS8 compared with CS4 samples. CS8 + R reversed CS8 effects and normalized the levels of oxidative stress. MALDI-IMS demonstrated striking CS-associated alterations in WM lipid profiles characterized by either reductions or increases in phospholipids (phosphatidylinositol, phosphatidylserine, phosphatidylcholine, or phosphatidylethanolamine) and sphingolipids (sulfatides), and partial reversal of CS's inhibitory effects with recovery. The heatmap hierarchical dendrogram and PCA distinguished CS exposure, duration, and withdrawal effects on WM lipid profiles. CONCLUSION: CS-mediated WM degeneration is associated with lipid peroxidation, protein oxidative injury, and alterations in myelin lipid composition, including shifts in phospholipids and sphingolipids needed for membrane integrity, plasticity, and intracellular signaling. Future goals are to delineate WM abnormalities in AD using MALDI-IMS, and couple the findings with MRI-mass spectroscopy to improve in vivo diagnostics and early detection of brain biochemical responses to treatment. PMID- 26836187 TI - Diagnostic Impact of Cerebrospinal Fluid Biomarker (Pre-)Analytical Variability in Alzheimer's Disease. AB - Intra- and inter-laboratory variability of cerebrospinal fluid (CSF) biomarker analyses remains an important issue. We investigated the clinical-diagnostic impact of CSF biomarker concentration shifts in mild cognitive impairment (MCI) and autopsy-confirmed Alzheimer's disease (AD) dementia patients. MCI patients (n = 85), autopsy-confirmed AD dementia patients (n = 72), and cognitively healthy controls (n = 100) were included in this prospective, longitudinal study. AD dementia patients were followed up until death, and controls were included from 1992 until 2003. In-house validated cutoff values of biomarkers were applied: Abeta1-42 <638.5 pg/mL, T-tau>296.5 pg/mL, P-tau(181P) >56.5 pg/mL. Both increments and decrements (from +/- 5% to +/- 40% ) were added to the true (=observed) CSF biomarker values, imitating the anticipated differences in biomarker concentrations. Within certain limits, the clinical diagnostic performance of AD CSF biomarkers remains largely unchanged and clinical diagnostic accuracy deviated less than 8.2% from the reference when concentration shifts ranging between -20% and +20% were added to one of the three CSF biomarkers in MCI and autopsy-confirmed AD patients. Notwithstanding the fact that (pre- and post-)analytical parameters can affect the clinical classification, the present exploratory study provides evidence that for a specific context of use, the impact on clinical accuracy of biomarker concentration shifts might be lower than originally expected. In conclusion, induced shifts of +/-20% in only one of the three biomarkers has limited impact on the clinical accuracy of AD CSF biomarkers in MCI and autopsy-confirmed AD patients when using the IWG-2 criteria. PMID- 26836188 TI - Gx-50 Inhibits Neuroinflammation via alpha7 nAChR Activation of the JAK2/STAT3 and PI3K/AKT Pathways. AB - Recent studies have revealed that the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR) is a critical link between inflammation and neurodegeneration, which is closely associated with Alzheimer's disease (AD). The JAK2/STAT3 and PI3K/AKT signaling pathways contribute to the neuroprotective and anti inflammatory effects of alpha7nAChR. Our previous studies have shown that treatment with gx-50 improves cognitive function and is neuroprotective. Here, we investigated the effect of gx-50 on alpha7 nAChR and Abeta-induced inflammation in microglia. First, the binding affinity of gx-50 to alpha7 nAChR was examined using the fluorescence-based Octet RED system, and the expression of alpha7 nAChR was detected using real-time PCR and western blotting. We also investigated downstream events of alpha7 nAChR activity, including the translocation of p STAT3 and the phosphorylation of JAK2, STAT3, PI3K, and AKT. Finally, the effect of gx-50 on Abeta-induced inflammation via alpha7 nAChR-mediated signaling pathways was investigated using cytokine assays. The results showed that gx-50 is able to act as a specific ligand to activate alpha7 nAChR, which then upregulates the JAK2/STAT3 and PI3K/AKT signaling pathways to inhibit the secretions of pro inflammatory cytokines, such as IL-1beta. In conclusion, the results suggest that gx-50 could inhibit the Abeta-induced inflammatory response in microglia via alpha7 nAChR activity, which might be a successful therapeutic target against AD. PMID- 26836189 TI - Spatial Memory Impairment is Associated with Intraneural Amyloid-beta Immunoreactivity and Dysfunctional Arc Expression in the Hippocampal-CA3 Region of a Transgenic Mouse Model of Alzheimer's Disease. AB - Dysfunction of synaptic communication in cortical and hippocampal networks has been suggested as one of the neuropathological hallmarks of the early stages of Alzheimer's disease (AD). Also, several lines of evidence have linked disrupted levels of activity-regulated cytoskeletal associated protein (Arc), an immediate early gene product that plays a central role in synaptic plasticity, with AD "synaptopathy". The mapping of Arc expression patterns in brain networks has been extensively used as a marker of memory-relevant neuronal activity history. Here we evaluated basal and behavior-induced Arc expression in hippocampal networks of the 3xTg-AD mouse model of AD. The basal percentage of Arc-expressing cells in 10 month-old 3xTg-AD mice was higher than wild type in CA3 (4.88% versus 1.77% , respectively) but similar in CA1 (1.75% versus 2.75% ). Noteworthy, this difference was not observed at 3 months of age. Furthermore, although a Morris water maze test probe induced a steep (~4-fold) increment in the percentage of Arc+ cells in the CA3 region of the 10-month-old wild-type group, no such increment was observed in age-matched 3xTg-AD, whereas the amount of Arc+ cells in CA1 increased in both groups. Further, we detected that CA3 neurons with amyloid-beta were much more likely to express Arc protein under basal conditions. We propose that in 3xTg-AD mice, intraneuronal amyloid-beta expression in CA3 could increase unspecific neuronal activation and subsequent Arc protein expression, which might impair further memory-stabilizing processes. PMID- 26836186 TI - Plasma Phospholipid and Sphingolipid Alterations in Presenilin1 Mutation Carriers: A Pilot Study. AB - BACKGROUND AND OBJECTIVE: Aberrant lipid metabolism has been implicated in sporadic Alzheimer's disease (AD). The current study investigated plasma phospholipid and sphingolipid profiles in individuals carrying PSEN1 mutations responsible for autosomal dominant AD (ADAD). METHODS: Study participants evaluated were from the Perth and Melbourne sites of the Dominantly Inherited Alzheimer Network (DIAN) study. Plasma phospholipid and sphingolipid profiles were measured using liquid chromatography coupled with mass spectrometry in 20 PSEN1 mutation carriers (MC; eight of whom were symptomatic and twelve asymptomatic, based on Clinical Dementia Rating scores) and compared with six non carriers (NC) using linear mixed models. Further, AD gold standard biomarker data obtained from the DIAN database were correlated with lipid species significantly altered between MC and NC, using Spearman's correlation coefficient. RESULTS: One hundred and thirty-nine plasma phospholipid and sphingolipid species were measured. Significantly altered species in MC compared to NC primarily belonged to choline and ethanolamine containing phospholipid classes and ceramides. Further phosphatidylcholine species (34:6, 36:5, 40:6) correlated with cerebrospinal fluid tau (p < 0.05), and plasmalogen ethanolamine species (34:2, 36:,4) correlated with both cerebrospinal fluid tau and brain amyloid load within the MC group (p < 0.05). CONCLUSION: These findings indicate altered phospholipid and sphingolipid metabolism in ADAD and provide insight into the pathomolecular changes occurring with ADAD pathogenesis. Further, findings reported in this study allow comparison of lipid alterations in ADAD with those reported previously in sporadic AD. The findings observed in the current pilot study warrant validation in the larger DIAN cohort. PMID- 26836190 TI - Three-Dimensional Eigenbrain for the Detection of Subjects and Brain Regions Related with Alzheimer's Disease. AB - BACKGROUND: Considering that Alzheimer's disease (AD) is untreatable, early diagnosis of AD from the healthy elderly controls (HC) is pivotal. However, computer-aided diagnosis (CAD) systems were not widely used due to its poor performance. OBJECTIVE: Inspired from the eigenface approach for face recognition problems, we proposed an eigenbrain to detect AD brains. Eigenface is only for 2D image processing and is not suitable for volumetric image processing since faces are usually obtained as 2D images. METHODS: We extended the eigenbrain to 3D. This 3D eigenbrain (3D-EB) inherits the fundamental strategies in either eigenface or 2D eigenbrain (2D-EB). All the 3D brains were transferred to a feature space, which encoded the variation among known 3D brain images. The feature space was named as the 3D-EB, and defined as eigenvectors on the set of 3D brains. We compared four different classifiers: feed-forward neural network, support vector machine (SVM) with linear kernel, polynomial (Pol) kernel, and radial basis function kernel. RESULTS: The 50x10-fold stratified cross validation experiments showed that the proposed 3D-EB is better than the 2D-EB. SVM with Pol kernel performed the best among all classifiers. Our "3D-EB + Pol-SVM" achieved an accuracy of 92.81% +/- 1.99% , a sensitivity of 92.07% +/- 2.48% , a specificity of 93.02% +/- 2.22% , and a precision of 79.03% +/- 2.37% . Based on the most important 3D-EB U1, we detected 34 brain regions related with AD. The results corresponded to recent literature. CONCLUSIONS: We validated the effectiveness of the proposed 3D-EB by detecting subjects and brain regions related to AD. PMID- 26836191 TI - Decreased Inter-Hemispheric Functional Connectivity in Cognitively Intact Elderly APOE E4 Carriers: A Preliminary Study. AB - The apolipoprotein E (APOE) E4 allele is the best-known genetic risk factor for developing sporadic Alzheimer's disease (AD). According to neuroimaging studies, the APOE E4 allele is associated with localized altered brain function. However, in long-range circuitry, APOE E4 allele-related alterations in functional communication between hemispheres have rarely been directly investigated. We examined the alteration of resting-state functional connectivity (RSFC) between inter-hemispheric homotopic regions in cognitively intact, elderly APOE E4 carriers. The voxel-mirrored homotopic connectivity method was used to assess the inter-hemispheric RSFC. The current study included 13 cognitively intact, elderly APOE E4 carriers (with at least one copy of APOE E4 allele) and 22 well-matched E3 homozygotes. Comparisons between the two groups were conducted, and subsequently, the correlation between the differential inter-hemispheric RSFC and cognitive ability was analyzed. Compared with E3 homozygotes, APOE E4 carriers showed decreased inter-hemispheric RSFC in the bilateral medial temporal lobe (MTL) and orbital frontal cortex (OFC). Moreover, in APOE E4 carriers, the inter hemispheric RSFC of the MTL correlated with the Wechsler Memory Scale-Logical Memory (WMS-LM) (immediate and delayed performance, r = 0.64, p < 0.05; r = 0.65, p < 0.05, respectively), and the inter-hemispheric RSFC of the OFC correlated with the WMS-LM delayed performance (r = 0.71, p < 0.05). In our study, the presence of the APOE E4 allele was linked with decreased inter hemispheric RSFC, which was attributed to memory performance in carriers. PMID- 26836192 TI - Posterior Accumulation of Tau and Concordant Hypometabolism in an Early-Onset Alzheimer's Disease Patient with Presenilin-1 Mutation. AB - It is unclear whether the distribution of tau pathology differs between cases with early-onset familial Alzheimer's disease (AD) and sporadic AD. We present positron emission tomography (PET) data from a young patient with a presenilin-1 mutation (Thr116Asn). 18F-flutemetamol PET showed a distribution of amyloid-beta fibrils similar to sporadic AD. However, the pattern of tau pathology, revealed using 18F-AV1451 PET, showed higher uptake in posterior cingulate, precuneus, parietal and occipital cortices compared to late-onset sporadic AD. Further, the tau pathology, but not amyloid pathology, exhibited a very clear inverse relationship with 18F-fluorodeoxyglucose-metabolism, indicating neuronal hypometabolism in regions affected by tau aggregates. PMID- 26836193 TI - T3D-959: A Multi-Faceted Disease Remedial Drug Candidate for the Treatment of Alzheimer's Disease. AB - BACKGROUND: T3D-959, a dual PPAR-delta/PPAR gamma nuclear receptor agonist and former diabetes drug candidate, has been repositioned as an Alzheimer's disease (AD)-modifying therapy. OBJECTIVE: This study examines the effectiveness and mechanisms of T3D-959's therapeutic effects using in vivo and ex vivo rat models of sporadic AD. METHODS: A sporadic AD model was generated by intracerebral (i.c.) administration of streptozotocin (STZ). Control and i.c. STZ treated rats were gavaged with saline or T3D-959 (0.3 to 3.0 mg/kg/day) for 28 days. Spatial learning and memory were evaluated using the Morris water maze test. Frontal lobe slice cultures generated 24 hours after i.c. STZ or vehicle were used to study early effects of T3D-959 (0.5-1.0 MUM) on viability and molecular markers of AD. RESULTS: T3D-959 significantly improved spatial learning and memory in i.c STZ treated rats. Mechanistically, T3D-959 significantly improved culture viability and brain morphology, reduced levels of oxidative stress and Abeta, and normalized expression of phospho-tau, choline acetyltransferase, and myelin associated glycoprotein. Protective effects occurred even at the lowest tested dose of T3D-959. CONCLUSIONS: Pre-clinical proof of concept has been demonstrated that T3D-959 can improve multiple pathologies of AD resulting in significant improvements in cognitive function and molecular and biochemical indices of neurodegeneration. These results support the theses that (1) effective disease modification in AD can be achieved by targeting relevant nuclear receptors, and (2) treating AD as a metabolic disease has the potential to be disease remedial. A Phase 2a trial of T3D-959 in mild-to-moderate AD patients has been initiated (ClinicalTrials.gov identifier NCT02560753). PMID- 26836194 TI - Overexpression of Metallothionein-1 Modulates the Phenotype of the Tg2576 Mouse Model of Alzheimer's Disease. AB - Alzheimer's disease (AD) is the most commonly diagnosed dementia, where signs of neuroinflammation and oxidative stress are prominent. In this study we intend to further characterize the roles of the antioxidant, anti-inflammatory, and heavy metal binding protein, metallothionein-1 (MT-1), by crossing Mt1 overexpressing mice with a well-known mouse model of AD, Tg2576 mice, which express the human amyloid-beta protein precursor (hAbetaPP) with the Swedish K670N/M671L mutations. Mt1 overexpression increased overall perinatal survival, but did not affect significantly hAbetaPP-induced mortality and weight loss in adult mice. Amyloid plaque burden in ~14-month-old mice was increased by Mt1 overexpression in the hippocampus but not the cortex. Despite full length hAbetaPP levels and amyloid plaques being increased by Mt1 overexpression in the hippocampus of both sexes, oligomeric and monomeric forms of Abeta, which may contribute more to toxicity, were decreased in the hippocampus of females and increased in males. Several behavioral traits such as exploration, anxiety, and learning were altered in Tg2576 mice to various degrees depending on the age and the sex. Mt1 overexpression ameliorated the effects of hAbetaPP on exploration in young females, and potentiated those on anxiety in old males, and seemed to improve the rate of spatial learning (Morris water maze) and the learning elicited by a classical conditioning procedure (eye-blink test). These results clearly suggest that MT-1 may be involved in AD pathogenesis. PMID- 26836196 TI - Hemisphere Asymmetry of Response to Pharmacologic Treatment in an Alzheimer's Disease Mouse Model. AB - The aim of this study was to examine hemisphere asymmetry of response to pharmacologic treatment in an Alzheimer's disease mouse model using cilostazol as a chemical stimulus. Eight-month-old mice were assigned to vehicle or cilostazol treatment for three months and hemispheres were analyzed using quantitative proteomics. Bioinformatics interpretation showed that following treatment, aggregation of blood platelets significantly decreased in the right hemisphere whereas neurodegeneration significantly decreased and synaptic transmission increased in the left hemisphere only. Our study provides novel evidence on cerebral laterality of pharmacologic activity, with important implications in deciphering regional pharmacodynamic effects of existing drugs thus uncovering novel hemisphere-specific therapeutic targets. PMID- 26836195 TI - Prion Protein-Hemin Interaction Upregulates Hemoglobin Synthesis: Implications for Cerebral Hemorrhage and Sporadic Creutzfeldt-Jakob Disease. AB - Hemin is known to induce endocytosis of prion-protein (PrP(C)) from the neuronal plasma membrane, potentially limiting propagation of the disease causing PrP scrapie (PrP(Sc)) isoform. Hemin is therefore an attractive disease-modifying option for sporadic Creutzfeldt-Jakob disease (sCJD), a human prion disorder with no effective treatment. The hemin-PrP(C) interaction is also of interest in cerebral-hemorrhage (CH), a condition where potentially toxic hemin molecules come in contact with neuronal PrP(C). Interestingly, PrP(C) is upregulated in penumbric neurons surrounding CH and is known to confer neuroprotection in a dose dependent manner. The underlying mechanism, however, is not clear. Here, we report that hemin binds PrP(C) on diverse cell lines, resulting in its aggregation or degradation in a cell-type specific manner. Surprisingly, the hemin-PrP(C) interaction upregulates Hb synthesis in hematopoietic cells, a response reversed by deleting the hemin-binding octa-peptide repeat region of PrP(C). A similar response is noted in brain organotypic cultures where exposure to hemin induces significantly more alpha-globin in wild-type (PrP(+/+)) relative to PrP-knock-out (PrP(-/-)) samples. Furthermore, red blood cells and brain tissue from PrP(-/-) mice show significantly less alpha-globin relative to PrP(+/+) controls, indicating a positive effect of PrP(C) on Hb synthesis under physiological conditions as well. Surprisingly, levels of alpha-globin are significantly higher in sCJD brain tissue relative to controls, suggesting compensatory upregulation of Hb synthesis by surviving neurons or misregulation in diseased brains. These observations reveal a unique function of PrP(C) that is likely to impact the therapeutic management of CH and sCJD. PMID- 26836197 TI - Nanoformulated alpha-mangostin ameliorates Alzheimer's disease neuropathology by elevating LDLR expression and accelerating amyloid-beta clearance. AB - Alzheimer's disease (AD), the most common form of dementia, is now representing one of the largest global healthcare challenges. However, an effective therapy is still lacking. Accumulation of amyloid-beta (Abeta) in the brain is supposed to trigger pathogenic cascades that eventually lead to AD. Therefore, Abeta clearance strategy is being actively pursued as a promising disease modifying therapy. Here, we found that alpha-mangostin (alpha-M), a polyphenolic xanthone derivative from mangosteen, up-regulated low density lipoprotein receptor (LDLR) expression in microglia and liver cells, and efficiently facilitated Abeta clearance. However, the in vivo application of alpha-M is limited due to its hydrophobic nature, poor aqueous solubility and stability, and thus low bioavailability and accumulation in the target organs. To overcome this limitation, alpha-M was encapsulated into the core of poly(ethylene glycol) poly(l-lactide) (PEG-PLA) nanoparticles [NP(alpha-M)]. Such nanoencapsulation improved the biodistribution of alpha-M in both the brain and liver, enhanced the brain clearance of (125)I-radiolabeled Abeta1-42 in an LDLR-dependent manner, reduced Abeta deposition, attenuated neuroinflammatory responses, ameliorated neurologic changes and reversed behavioral deficits in AD model mice. These findings justified the concept that polyphenol-mediated modulation of LDLR expression might serve as a safe and efficient disease-modifying therapy for AD by accelerating Abeta clearance. It also demonstrated the powerful capacity of nanotechnology in modulating the biodistribution behavior of drug to improve its therapeutic efficacy in AD. PMID- 26836198 TI - Biogenesis of Plant Prevacuolar Multivesicular Bodies. AB - Plant prevacuolar compartments (PVCs), or multivesicular bodies (MVBs), are single membrane-bound organelles that play important roles in mediating protein trafficking to vacuoles in the secretory pathway. PVC/MVB also serves as a late endosome in the endocytic pathway in plants. Since the plant PVC was identified as an MVB more than 10 years ago, great progress has been made toward the understanding of PVC/MVB function and biogenesis in plants. In this review, we first summarize previous research into the identification and characterization of plant PVCs/MVBs, and then highlight recent advances on the mechanisms underlying intraluminal vesicle formation and maturation of plant PVCs/MVBs. In addition, we discuss the possible crosstalk that appears to occur between PVCs/MVBs and autophagosomes during autophagy in plants. Finally, we list some open questions and present future perspectives in this field. PMID- 26836199 TI - Antiemetic medication for prevention and treatment of chemotherapy-induced nausea and vomiting in childhood. AB - BACKGROUND: Nausea and vomiting remain a problem for children undergoing treatment for malignancies despite new antiemetic therapies. Optimising antiemetic regimens could improve quality of life by reducing nausea, vomiting, and associated clinical problems. This is an update of the original systematic review. OBJECTIVES: To assess the effectiveness and adverse events of pharmacological interventions in controlling anticipatory, acute, and delayed nausea and vomiting in children and young people (aged less than 18 years) about to receive or receiving chemotherapy. SEARCH METHODS: Searches included the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, PsycINFO, conference proceedings of the American Society of Clinical Oncology, International Society of Paediatric Oncology, Multinational Association of Supportive Care in Cancer, and ISI Science and Technology Proceedings Index from incept to December 16, 2014, and trial registries from their earliest records to December 2014. We examined references of systematic reviews and contacted trialists for information on further studies. We also screened the reference lists of included studies. SELECTION CRITERIA: Two review authors independently screened abstracts in order to identify randomised controlled trials (RCTs) that compared a pharmacological antiemetic, cannabinoid, or benzodiazepine with placebo or any alternative active intervention in children and young people (less than 18 years) with a diagnosis of cancer who were to receive chemotherapy. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted outcome and quality data from each RCT. When appropriate, we undertook meta-analysis. MAIN RESULTS: We included 34 studies that examined a range of different antiemetics, used different doses and comparators, and reported a variety of outcomes. The quality and quantity of included studies limited the exploration of heterogeneity to narrative approaches only.The majority of quantitative data related to the complete control of acute vomiting (27 studies). Adverse events were reported in 29 studies and nausea outcomes in 16 studies.Two studies assessed the addition of dexamethasone to 5-HT3 antagonists for complete control of vomiting (pooled risk ratio (RR) 2.03; 95% confidence interval (CI) 1.35 to 3.04). Three studies compared granisetron 20 mcg/kg with 40 mcg/kg for complete control of vomiting (pooled RR 0.93; 95% CI 0.80 to 1.07). Three studies compared granisetron with ondansetron for complete control of acute nausea (pooled RR 1.05; 95% CI 0.94 to 1.17; 2 studies), acute vomiting (pooled RR 2.26; 95% CI 2.04 to 2.51; 3 studies), delayed nausea (pooled RR 1.13; 95% CI 0.93 to 1.38; 2 studies), and delayed vomiting (pooled RR 1.13; 95% CI 0.98 to 1.29; 2 studies). No other pooled analyses were possible.Narrative synthesis suggests that 5-HT3 antagonists are more effective than older antiemetic agents, even when these agents are combined with a steroid. Cannabinoids are probably effective but produce frequent side effects. AUTHORS' CONCLUSIONS: Our overall knowledge of the most effective antiemetics to prevent chemotherapy-induced nausea and vomiting in childhood is incomplete. Future research should be undertaken in consultation with children, young people, and families that have experienced chemotherapy and should make use of validated, age appropriate measures. This review suggests that 5-HT3 antagonists are effective in patients who are to receive emetogenic chemotherapy, with granisetron or palonosetron possibly better than ondansetron. Adding dexamethasone improves control of vomiting, although the risk-benefit profile of adjunctive steroid remains uncertain. PMID- 26836200 TI - Contaminant source reconstruction by empirical Bayes and Akaike's Bayesian Information Criterion. AB - The objective of the paper is to present an empirical Bayesian method combined with Akaike's Bayesian Information Criterion (ABIC) to estimate the contaminant release history of a source in groundwater starting from few concentration measurements in space and/or in time. From the Bayesian point of view, the ABIC considers prior information on the unknown function, such as the prior distribution (assumed Gaussian) and the covariance function. The unknown statistical quantities, such as the noise variance and the covariance function parameters, are computed through the process; moreover the method quantifies also the estimation error through the confidence intervals. The methodology was successfully tested on three test cases: the classic Skaggs and Kabala release function, three sharp releases (both cases regard the transport in a one dimensional homogenous medium) and data collected from laboratory equipment that consists of a two-dimensional homogeneous unconfined aquifer. The performances of the method were tested with two different covariance functions (Gaussian and exponential) and also with large measurement error. The obtained results were discussed and compared to the geostatistical approach of Kitanidis (1995). PMID- 26836201 TI - Bone ingrowth of various porous titanium scaffolds produced by a moldless and space holder technique: an in vivo study in rabbits. AB - Porous titanium has long been desired as a bone substitute material because of its ability to reduce the stress shielding in supporting bone. In order to achieve the various pore structures, we have evolved a moldless process combined with a space holder technique to fabricate porous titanium. This study aims to evaluate which pore size is most suitable for bone regeneration using our process. The mixture comprising Ti powder, wax binder and PMMA spacer was prepared manually at 70 degrees C which depended on the mixing ratio of each group. Group 1 had an average pore size of 60 MUm, group 2 had a maximum pore size of 100 MUm, group 3 had a maximum pore size of 200 MUm and group 4 had a maximum pore size of 600 MUm. These specimens were implanted into rabbit calvaria for three and 20 weeks. Thereafter, histomorphometrical evaluation was performed. In the histomorphometrical evaluation after three weeks, the group with a 600 MUm pore size showed a tendency to greater bone ingrowth. However, after 20 weeks the group with a pore size of 100 MUm showed significantly greater bone ingrowth than the other groups. This study suggested that bone regeneration into porous titanium scaffolds is pore size-dependent, while bone ingrowth was most prominent for the group with 100 MUm-sized pores after 20 weeks in vivo. PMID- 26836202 TI - Update: Malaria, U.S. Armed Forces, 2015. AB - U.S. service members are at risk of acquiring malaria infection when they are located in endemic areas because of long-term duty assignments, participation in shorter-term contingency operations, or personal travel. The number of malaria cases among U.S. military service members in 2015 (n=30) was the lowest annual count in at least 20 years and follows 3 previous years of greatly reduced incidence. The relatively low numbers of cases during 2012-2015 mainly reflect decreases in cases acquired in Afghanistan as the number of troops who served in Afghanistan sharply diminished in those years. About 43% of the 2015 cases were caused by Plasmodium falciparum (n=13) and 13% by Plasmodium vivax (n=4); about one-third of cases (37%) were reported as "unspecified" malaria. Malaria was diagnosed at or reported from 21 different medical facilities in the U.S., Afghanistan, Germany, and Korea. Providers of health care to military members should be knowledgeable regarding, and vigilant for, clinical presentations of malaria outside of endemic areas. PMID- 26836203 TI - Durations of service until first and recurrent episodes of clinically significant back pain, active component military members: changes among new accessions to service since calendar year 2000. AB - This report summarizes frequencies and timing of first and recurrent episodes of back pain treated in the U.S. Military Health System among more than 2 million military members who began active service between July 2000 and June 2012. In the population overall, at least 5% were affected by clinically significant back pain within 6 months and 10% within 13 months of beginning active service; and 34% had at least one episode of back pain while in active service during the surveillance period. After initial episodes of back pain, more than half (54%) of those affected had at least one recurrent episode; and after first recurrences, 65% had second recurrences while still in active service. In general, back pain episode free periods preceding initial and between successive episodes markedly decreased during the period. Frequencies and timing of back pain episodes varied in relation to service branch, gender, and occupation. Acute back pain is a common disorder that is unpredictable in onset and often debilitating. Its prevention should be a military medical research objective of high priority. PMID- 26836204 TI - Surveillance snapshot: Responses to questions about back pain in post-deployment health assessment questionnaires, U.S. Armed Forces, 2005-2014. PMID- 26836205 TI - A structural and functional magnetic resonance imaging dataset of brain tumour patients. AB - We collected high resolution structural (T1, T2, DWI) and several functional (BOLD T2*) MRI data in 22 patients with different types of brain tumours. Functional imaging protocols included a motor task, a verb generation task, a word repetition task and resting state. Imaging data are complemented by demographics (age, sex, handedness, and pathology), behavioural results to motor and cognitive tests and direct cortical electrical stimulation data (pictures of stimulation sites with outcomes) performed during surgery. Altogether, these data are suited to test functional imaging methods for single subject analyses, in particular methods that focus on locating eloquent cortical areas, critical functional and/or structural network hubs, and predict patient status based on imaging data (presurgical mapping). PMID- 26836206 TI - Disposable sheath that facilitates endoscopic Raman spectroscopy. AB - In vivo endoscopic Raman spectroscopy of human tissue using a fiber optic probe has been previously demonstrated. However, there remain several technical challenges, such as a robust control over the laser radiation dose and measurement repeatability during endoscopy. A decrease in the signal to noise was also observed due to aging of Raman probe after repeated cycles of harsh reprocessing procedures. To address these issues, we designed and tested a disposable, biocompatible, and sterile sheath for use with a fiber optic endoscopic Raman probe. The sheath effectively controls contamination of Raman probes between procedures, greatly reduces turnaround time, and slows down the aging of the Raman probes. A small optical window fitted at the sheath cap maintained the measurement distance between Raman probe end and tissue surface. To ensure that the sheath caused a minimal amount of fluorescence and Raman interference, the optical properties of materials for the sheath, optical window, and bonding agent were studied. The easy-to-use sheath can be manufactured at a moderate cost. The sheath strictly enforced a maximum permissible exposure standard of the tissue by the laser and reduced the spectral variability by 1.5 to 8.5 times within the spectral measurement range. PMID- 26836207 TI - Minimally invasive surgical method to detect sound processing in the cochlear apex by optical coherence tomography. AB - Sound processing in the inner ear involves separation of the constituent frequencies along the length of the cochlea. Frequencies relevant to human speech (100 to 500 Hz) are processed in the apex region. Among mammals, the guinea pig cochlear apex processes similar frequencies and is thus relevant for the study of speech processing in the cochlea. However, the requirement for extensive surgery has challenged the optical accessibility of this area to investigate cochlear processing of signals without significant intrusion. A simple method is developed to provide optical access to the guinea pig cochlear apex in two directions with minimal surgery. Furthermore, all prior vibration measurements in the guinea pig apex involved opening an observation hole in the otic capsule, which has been questioned on the basis of the resulting changes to cochlear hydrodynamics. Here, this limitation is overcome by measuring the vibrations through the unopened otic capsule using phase-sensitive Fourier domain optical coherence tomography. The optically and surgically advanced method described here lays the foundation to perform minimally invasive investigation of speech-related signal processing in the cochlea. PMID- 26836208 TI - Toward noninvasive assessment of flap viability with time-resolved diffuse optical tomography: a preclinical test on rats. AB - The noninvasive assessment of flap viability in autologous reconstruction surgery is still an unmet clinical need. To cope with this problem, we developed a proof of-principle fully automatized setup for fast time-gated diffuse optical tomography exploiting Mellin-Laplace transform to obtain three-dimensional tomographic reconstructions of oxy- and deoxy-hemoglobin concentrations. We applied this method to perform preclinical tests on rats inducing total venous occlusion in the cutaneous abdominal flaps. Notwithstanding the use of just four source-detector couples, we could detect a spatially localized increase of deoxyhemoglobin following the occlusion (up to 550 MUM in 54 min). Such capability to image spatio-temporal evolution of blood perfusion is a key issue for the noninvasive monitoring of flap viability. PMID- 26836209 TI - Blinking supervision in a working environment. AB - The health of the ocular surface requires blinks of the eye to be frequent in order to provide moisture and to renew the tear film. However, blinking frequency has been shown to decrease in certain conditions such as when subjects are conducting tasks with high cognitive and visual demands. These conditions are becoming more common as people work or spend their leisure time in front of video display terminals. Supervision of blinking frequency in such environments is possible, thanks to the availability of computer-integrated cameras. Therefore, the aim of the present study is to develop an algorithm for the detection of eye blinks and to test it, in a number of videos captured, while subjects are conducting a variety of tasks in front of the computer. The sensitivity of the algorithm for blink detection was found to be of 87.54% (range 30% to 100%), with a mean false-positive rate of 0.19% (range 0% to 1.7%), depending on the illumination conditions during which the image was captured and other computer user spatial configurations. The current automatic process is based on a partly modified pre-existing eye detection and image processing algorithms and consists of four stages that are aimed at eye detection, eye tracking, iris detection and segmentation, and iris height/width ratio assessment. PMID- 26836211 TI - Errata: Advantages of microscope-integrated intraoperative online optical coherence tomography: usage in Boston keratoprosthesis type I surgery. PMID- 26836210 TI - Using thermographic cameras to investigate eye temperature and clinical severity in depression. AB - Previous studies suggest that altered corneal temperature may be a feature of schizophrenia, but the association between major depressive disorder (MDD) and corneal temperature has yet to be assessed. The aim of this study is to investigate whether eye temperature is different among MDD patients than among healthy individuals. We used a thermographic camera to measure and compare the temperature profile across the corneas of 16 patients with MDD and 16 age- and sex-matched healthy subjects. We found that the average corneal temperature between the two groups did not differ statistically, although clinical severity correlated positively with right corneal temperature. Corneal temperature may be an indicator of clinical severity in psychiatric disorders, including depression. PMID- 26836213 TI - Corrigendum. PMID- 26836212 TI - A DIVA vaccine for cross-protection against Salmonella. AB - Swine are often asymptomatic carriers of Salmonella spp., a leading cause of human bacterial foodborne disease. Vaccination against Salmonella is effective for protecting animal health and enhancing food safety. However, with >2500 Salmonella serovars, current vaccines for swine offer limited cross-protection against heterologous serovars. Also, existing vaccines can interfere with surveillance programs that monitor the Salmonella status of swine herds. To overcome Salmonella vaccine limitations, we rationally designed and constructed an attenuated Salmonella enterica serovar Typhimurium vaccine (BBS 866) by deleting multiple small regulatory RNA (sRNA) genes (omrA, omrB, rybB, micA, and invR) in combination with an rfaH mutation. We vaccinated swine intranasally at 3 weeks of age with PBS (mock-vaccinated), BBS 866 or BBS 202 (S. Typhimurium rfaH, Bearson et al., Front Vet Sci 2014;1:9.) and challenged at 7-weeks of age with virulent S. Choleraesuis, a swine pathogen. Vaccination with BBS 866 enhanced protection against S. Choleraesuis by significantly limiting the duration of fever, weight loss, the levels of circulating INFgamma, and the total number of swine with S. Choleraesuis septicemia. Vaccination with either BBS 866 or BBS 202 significantly reduced S. Choleraesuis colonization of both systemic (spleen and liver) and gastrointestinal (Peyer's Patch, Ileocecal lymph nodes, and cecum) tissues. Similar to our earlier report for BBS 202, the BBS 866 vaccine strain can be used in swine without compromising the differentiation of infected from vaccinated animals (DIVA). Therefore, the attenuated S. Typhimurium BBS 866 strain, containing mutations in rfaH and multiple sRNAs, addresses the limitations of current Salmonella vaccines by providing cross-protection against Salmonella serovars in swine without interfering with established monitoring programs for Salmonella surveillance. PMID- 26836214 TI - An In Vitro Attempt for Controlling Severe Phytopathogens and Human Pathogens Using Essential Oils from Mediterranean Plants of Genus Schinus. AB - Growing concerns about food safety and environmental protection enhanced the need for new and safe plant disease control strategies. The chemical composition of the three essential oils (EOs) extracted from leaves and fruits of Schinus terebinthifolius and leaves of Schinus molle, growing in Tunisia, was studied by GC and GC-MS. In all, 12 compounds were identified. The oils were mainly composed of terpene compounds. alpha-Pinene, alpha-phellandrene, and D-limonene were the major constituents. The aim of the current study was to evaluate the in vitro antimicrobial effectiveness of three EOs derived from plants of genus Schinus and extracted from leaves and fruits of S. terebinthifolius and leaves of S. molle. Both antifungal and antibacterial activities of the EOs were examined. The antifungal activity of the studied EOs was investigated against Colletotrichum acutatum and Botrytis cinerea in comparison with the systemic fungicide azoxystrobin used at 0.8 MUL mL(-1). The antibacterial activity was evaluated against three strains of Gram-positive (G+ve) bacteria (Bacillus megaterium, Bacillus mojavensis and Clavibacter michiganensis) and four strains of Gram negative (G-ve) bacteria (Escherichia coli, Xanthomonas campestris, Pseudomonas savastanoi, and Pseudomonas syringae pv. phaseolicola) compared with the synthetic antibiotic tetracycline at a concentration of 1600 MUg mL(-1). The minimum inhibitory concentration of the studied EOs has been evaluated against the above microorganisms using the 96-well microplate method. Tested microorganisms exhibited different levels of sensitivity to each tested EO. All investigated EOs reduced the fungal mycelial growth when used at low concentrations from 250 to 1000 ppm and from 2000 to 8000 ppm against C. acutatum and B. cinerea, respectively. Higher concentrations of the same EOs exhibited a fungicidal effect against both mitosporic fungi. The EO extracted from leaves of S. terebinthifolius significantly inhibited the growth of tested bacterial strains. Nevertheless, E. coli showed a weak resistance toward the same EO and a high resistance toward the other two tested EOs. Finally, P. savastanoi and P. syringae pv. phaseolicola showed a high resistance toward all tested EOs. PMID- 26836215 TI - Early Vasospasm after Aneurysmal Subarachnoid Hemorrhage Predicts the Occurrence and Severity of Symptomatic Vasospasm and Delayed Cerebral Ischemia. AB - BACKGROUND: Cerebral vasospasm usually develops several days after subarachnoid hemorrhage (SAH) and is generally acknowledged as a strong outcome predictor. In contrast, much less is known about the nature and eventual consequences of early angiographic vasospasm (EAVS) seen on admission digital subtraction angiography (DSA). Therefore, we aimed at identifying the risk factors and clinical impact of EAVS after SAH. METHODS: Five hundred and thirty-one SAH patients with admission DSA performed within 72 h after the bleeding event were selected from a comprehensive database containing all consecutive SAH patients treated at our institution between January 2005 and December 2012. Predictors of EAVS, as well as associations between EAVS and delayed vasospasm-related complications, and unfavorable outcome (defined as modified Rankin scale >3) were evaluated in univariate and multivariate analyses. RESULTS: EAVS was seen on 60 DSAs (11.3%) and was independently correlated with delayed symptomatic vasospasm requiring intra-arterial spasmolysis (OR 5.24, p < 0.0001), angioplasty (OR 2.56, p = 0.015) and repetitive endovascular treatment (OR 4.71, p < 0.0001). EAVS also increased the risk for multiple versus single territorial infarction on the follow-up CT scan(s) (OR 2.04, p = 0.047) and independently predicted unfavorable outcome (OR 2.93, p = 0.008). The presence of radiographic signs suspicious for fibromuscular dysplasia were independently associated with the occurrence of EAVS (OR 2.98, p = 0.026) and the need for repetitive endovascular vasospasm treatment (OR 3.95, p = 0.019). CONCLUSIONS: In view of the strong correlation with delayed symptomatic vasospasm and its ischemic complications, EAVS can be considered an alerting signal for severe symptomatic vasospasm. Therefore, more attention should be paid to the presence of EAVS on admission DSA. PMID- 26836216 TI - Well-defined hydroxyethyl starch-10-hydroxy camptothecin super macromolecule conjugate: cytotoxicity, pharmacodynamics research, tissue distribution test and intravenous injection safety assessment. AB - 10-Hydroxy camptothecin (10-HCPT) is an antitumor agent effective in the treatment of several solid tumors but its use is hampered by poor water solubility, low lactone stability, short plasma half-life and dose-limiting toxicity. These limits of 10-HCPT had been overcome by our group through preparing super macromolecule prodrug: 10-HCPT-hydroxyethyl starch (HES) conjugate. In this study, we mainly evaluated in vitro and in vivo behavior of the prodrug, containing cytotoxicity assay, pharmacodynamics study, vascular irritation test, hemolysis experiment and tissue distribution test of rats. The irritation test results achieved much lower irritation than the commercial injection. The tissue distribution results showed that HES-10-HCPT conjugate increased significantly the 10-HCPT concentration in the tumor, liver and spleen site, whereas decreased the drug concentration in the heart and kidney. The hemolysis effect of the prepared conjugate was not obvious. The pharmacodynamics results indicated that HES-10-HCPT prodrug had a better antitumor efficiency against mice with H22 tumor than the commercial injection, and the inhibition ratio of tumor was 85.2% and 31.1%, respectively at the same dosage. These findings suggest that HES-10-HCPT prodrug is a promising drug delivery system providing improved good injection safety, greater tolerance and antitumor effect. PMID- 26836217 TI - International linkage of two food-borne hepatitis A clusters through traceback of mussels, the Netherlands, 2012. AB - This report describes an outbreak investigation starting with two closely related suspected food-borne clusters of Dutch hepatitis A cases, nine primary cases in total, with an unknown source in the Netherlands. The hepatitis A virus (HAV) genotype IA sequences of both clusters were highly similar (459/460 nt) and were not reported earlier. Food questionnaires and a case-control study revealed an association with consumption of mussels. Analysis of mussel supply chains identified the most likely production area. International enquiries led to identification of a cluster of patients near this production area with identical HAV sequences with onsets predating the first Dutch cluster of cases. The most likely source for this cluster was a case who returned from an endemic area in Central America, and a subsequent household cluster from which treated domestic sewage was discharged into the suspected mussel production area. Notably, mussels from this area were also consumed by a separate case in the United Kingdom sharing an identical strain with the second Dutch cluster. In conclusion, a small number of patients in a non-endemic area led to geographically dispersed hepatitis A outbreaks with food as vehicle. This link would have gone unnoticed without sequence analyses and international collaboration. PMID- 26836218 TI - A model-based approach to assess the exposure-response relationship of Lorenzo's oil in adrenoleukodystrophy. AB - AIMS: X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder, most commonly affecting boys, associated with increased very long chain fatty acids (C26:0) in all tissues, causing cerebral demyelination and adrenocortical insufficiency. Certain monounsaturated long chain fatty acids including oleic and erucic acids, known as Lorenzo's oil (LO), lower plasma C26:0 levels. The aims of this study were to characterize the effect of LO administration on plasma C26:0 concentrations and to determine whether there is an association between plasma concentrations of erucic acid or C26:0 and the likelihood of developing brain MRI abnormalities in asymptomatic boys. METHODS: Non-linear mixed effects modelling was performed on 2384 samples collected during an open label single arm trial. The subjects (n = 104) were administered LO daily at ~2-3 mg kg(-1) with a mean follow-up of 4.88 +/- 2.76 years. The effect of erucic acid exposure on plasma C26:0 concentrations was characterized by an inhibitory fractional Emax model. A Weibull model was used to characterize the time-to-developing MRI abnormality. RESULTS: The population estimate for the fractional maximum reduction of C26:0 plasma concentrations was 0.76 (bootstrap 95% CI 0.73, 0.793). Our time-to-event analyses showed that every mg l(-1) increase in time-weighted average of erucic acid and C26:0 plasma concentrations was, respectively, associated with a 3.7% reduction and a 753% increase in the hazard of developing MRI abnormality. However, the results were not significant (P = 0.5344, 0.1509, respectively). CONCLUSIONS: LO administration significantly reduces the abnormally high plasma C26:0 concentrations in X-ALD patients. Further studies to evaluate the effect of LO on the likelihood of developing brain MRI abnormality are warranted. PMID- 26836219 TI - Comparative effectiveness research in the USA: when will there be an impact on healthcare decision-making? AB - Five annual surveys of healthcare decision-makers potentially affected by comparative effectiveness research (CER) indicate sustained recognition of its importance and potential impact. Initial expectations of immediate CER impact have over time turned to stakeholder assessments of little short-term impact. In successive surveys, they project a continuous horizon of 3-5 years for CER to have a moderate or substantial improvement in decision making. The prominence of Patient-Centered Outcomes Research Institute in CER is highlighted by stakeholders, but greater emphasis on translating and disseminating research findings is needed, a role in which Agency for Healthcare Research and Quality is expected to contribute. Stakeholders, including patients, must be engaged throughout to ensure that findings provide the flexibility for decision makers to apply them to their patient populations. PMID- 26836220 TI - National Cluster-Randomized Trial of Duty-Hour Flexibility in Surgical Training. AB - BACKGROUND: Concerns persist regarding the effect of current surgical resident duty-hour policies on patient outcomes, resident education, and resident well being. METHODS: We conducted a national, cluster-randomized, pragmatic, noninferiority trial involving 117 general surgery residency programs in the United States (2014-2015 academic year). Programs were randomly assigned to current Accreditation Council for Graduate Medical Education (ACGME) duty-hour policies (standard-policy group) or more flexible policies that waived rules on maximum shift lengths and time off between shifts (flexible-policy group). Outcomes included the 30-day rate of postoperative death or serious complications (primary outcome), other postoperative complications, and resident perceptions and satisfaction regarding their well-being, education, and patient care. RESULTS: In an analysis of data from 138,691 patients, flexible, less-restrictive duty-hour policies were not associated with an increased rate of death or serious complications (9.1% in the flexible-policy group and 9.0% in the standard-policy group, P=0.92; unadjusted odds ratio for the flexible-policy group, 0.96; 92% confidence interval, 0.87 to 1.06; P=0.44; noninferiority criteria satisfied) or of any secondary postoperative outcomes studied. Among 4330 residents, those in programs assigned to flexible policies did not report significantly greater dissatisfaction with overall education quality (11.0% in the flexible-policy group and 10.7% in the standard-policy group, P=0.86) or well-being (14.9% and 12.0%, respectively; P=0.10). Residents under flexible policies were less likely than those under standard policies to perceive negative effects of duty-hour policies on multiple aspects of patient safety, continuity of care, professionalism, and resident education but were more likely to perceive negative effects on personal activities. There were no significant differences between study groups in resident-reported perception of the effect of fatigue on personal or patient safety. Residents in the flexible-policy group were less likely than those in the standard-policy group to report leaving during an operation (7.0% vs. 13.2%, P<0.001) or handing off active patient issues (32.0% vs. 46.3%, P<0.001). CONCLUSIONS: As compared with standard duty-hour policies, flexible, less-restrictive duty-hour policies for surgical residents were associated with noninferior patient outcomes and no significant difference in residents' satisfaction with overall well-being and education quality. (FIRST ClinicalTrials.gov number, NCT02050789.). PMID- 26836221 TI - The Air Quality Health Index and Emergency Department Visits for Otitis Media. AB - PURPOSE: The purpose of this study was to explore novel multipollutant exposure assessments using the Air Quality Health Index in relation to emergency department visits for otitis media (OM). DESIGN: This study was a retrospective analysis using information from emergency department visits for OM, air pollution, and weather databases. METHODS: For children 3 years of age or younger, there were 4,815 emergency department visits for OM over a 6-year period across hospitals in Windsor, Ontario, Canada. Both time-stratified case-crossover and nonlinear time series distributed lag analyses were applied to investigate the association between the Air Quality Health Index and visits for OM. FINDINGS: Using case-crossover analysis, there was an increase in emergency department visits with OM diagnoses 6 to 7 days postexposure to increased ozone and 3 to 4 days after exposure to increased particulate matter. For every 1 unit increase in the Air Quality Health Index, discharge diagnosis of OM increased 5% to 6% three days postexposure. Effects were stronger using the nonlinear time series analysis. The overall risk for OM, in the first 15 days after an increase in the Air Quality Health Index, was 1.22 times the risk of OM on days following no increase in exposures. CONCLUSIONS: These findings confirm that there is an association between the multipollutant Air Quality Health Index and emergency department visits for OM. The findings can be used to inform risk communication, patient education, and policy. CLINICAL RELEVANCE: Clinicians can use the Air Quality Health Index as an education and advocacy tool to promote and protect the health of those at high risk for OM to reduce exposures. PMID- 26836223 TI - Intramolecular Singlet Fission in Oligoacene Heterodimers. AB - We investigate singlet fission (SF) in heterodimers comprising a pentacene unit covalently bonded to another acene as we systematically vary the singlet and triplet pair energies. We find that these energies control the SF process, where dimers undergo SF provided that the resulting triplet pair energy is similar or lower in energy than the singlet state. In these systems the singlet energy is determined by the lower-energy chromophore, and the rate of SF is found to be relatively independent of the driving force. However, triplet pair recombination in these heterodimers follows the energy gap law. The ability to tune the energies of these materials provides a key strategy to study and design new SF materials-an important process for third-generation photovoltaics. PMID- 26836222 TI - Abducens ocular neuromyotonia as a delayed complication of oropharyngeal carcinoma treated with radiation. AB - BACKGROUND: Ocular neuromyotonia (ONM) is a disorder characterized by periodic involuntary extraocular muscle contraction that occurs almost exclusively in the setting of prior radiation to the sella or skull base. We present the first case of abducens neuromyotonia associated with oropharyngeal carcinoma. METHODS AND RESULTS: We report a case of a 63-year-old patient with abducens ONM occurring 16 years after radiation treatment for oropharyngeal squamous cell carcinoma. A literature review was performed using Medline and PubMed databases to search for all documented cases of abducens neuromyotonia. Our review found 20 cases of abducens neuromyotonia but none after radiotherapy (RT) to the oropharynx. CONCLUSION: Abducens ONM can occur because of disease at anatomic locations remote from the course of the sixth cranial nerve, most likely because of the irradiated area exceeding the intended field. Our case also supports the fact that RT can significantly precede symptom onset. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2428-E2431, 2016. PMID- 26836224 TI - Lateral-Structure Single-Crystal Hybrid Perovskite Solar Cells via Piezoelectric Poling. AB - Single-crystal perovskite solar cells with a lateral structure yield an efficiency enhancement 44-fold that of polycrystalline thin films, due to the much longer carrier diffusion length. A piezoelectric effect observed in perovskite single-crystal and the strain-generated grain-boundaries enable ion migration to form a p-i-n structure. PMID- 26836226 TI - Toward Optimum Benefit-Risk and Reduced Access Lag For Cancer Drugs in Asia: A Global Development Framework Guided by Clinical Pharmacology Principles. PMID- 26836229 TI - Clinical significance of serum Wisteria floribunda agglutinin positive Mac-2 binding protein level in non-alcoholic steatohepatitis. AB - AIM: To examine the relationship between the Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+ -M2BP) level and histological findings for patients with non-alcoholic steatohepatitis (NASH). METHODS: A total of 134 NASH patients (mean age, 51.7 years) were analyzed. We examined the effect of WFA+ M2BP level on severity of liver fibrosis comparing with other laboratory markers, including aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, AST to platelet ratio index (APRI), FIB-4 index, platelet count and hyaluronic acid as serum liver fibrosis markers. Receiver-operator curve (ROC) analysis was performed for calculating the area under the ROC (AUROC). RESULTS: The WFA+ -M2B P-value ranged from 0.2 cut-off index (COI) to 9.6 COI (median, 0.9). The median values in each fibrosis stage were: 0.7 COI in F1, 0.7 COI in F2, 1.2 COI in F3 and 2.4 COI in F4 (P < 0.001). For predicting liver cirrhosis (F4), WFA+ -M2BP level had the AUROC of 0.854 (sensitivity, 69.2%; specificity, 88.4%) and for predicting advanced liver fibrosis (>=F3), WFA+ -M2BP level yielded the second highest AUROC with a level of 0.842 (sensitivity, 73.7%; specificity, 80.2%) and for predicting significant liver fibrosis (>=F2), WFA+ M2BP level yielded the highest AUROC with a level of 0.663 (sensitivity, 47.2%; specificity, 78.6%) among six liver fibrosis markers. The median values in patients with ballooning scores 1 (n = 58) and 2 (n = 76) were 0.6 and 1.1 COI, respectively (P < 0.001). CONCLUSION: Serum WFA+ -M2BP level can be useful for assessing liver histological findings in patients with NASH. PMID- 26836228 TI - A Role for the Placenta in Programming Maternal Mood and Childhood Behavioural Disorders. AB - Substantial data demonstrate that the early-life environment, including in utero, plays a key role in later life disease. In particular, maternal stress during pregnancy has been linked to adverse behavioural and emotional outcomes in children. Data from human cohort studies and experimental animal models suggest that modulation of the developing epigenome in the foetus by maternal stress may contribute to the foetal programming of disease. Here, we summarise insights gained from recent studies that may advance our understanding of the role of the placenta in mediating the association between maternal mood disorders and offspring outcomes. First, the placenta provides a record of exposures during pregnancy, as indicated by changes in the placental trancriptome and epigenome. Second, prenatal maternal mood may alter placental function to adversely impact foetal and child development. Finally, we discuss the less well established but interesting possibility that altered placental function, more specifically changes in placental hormones, may adversely affect maternal mood and later maternal behaviour, which can also have consequence for offspring well-being. PMID- 26836230 TI - Fifty Shades Flipped: Effects of Reading Erotica Depicting a Sexually Dominant Woman Compared to a Sexually Dominant Man. AB - The present study examined the effects of reading submission- and dominance themed erotica on attitudes toward women and rape, ideal partner preferences, and subjective sexual arousal. Heterosexual male (n = 241) and female (n = 240) participants read one of three erotic stories depicting male dominance, female dominance, or no dominance, or a fourth nonerotic control story. First, we found that after reading about a sexually dominant man, women reported increased benevolent sexism compared to men, and men reported increased rape myth acceptance compared to women. Second, men and women showed a similar level of preference for partner dominance after reading about a sexually dominant woman. This was in contrast to the typical pattern revealed in all other conditions, whereby women were more likely to favor dominant partners relative to men. Finally, we found no evidence to support the hypothesis that the story describing male dominance would be the most arousing. Rather, all three erotic stories were equally sexually arousing compared to the control condition, and men and women did not differ in the extent to which the erotic stories aroused them. Theoretical and practical implications are discussed. PMID- 26836227 TI - Tackling the 'dyslexia paradox': reading brain and behavior for early markers of developmental dyslexia. AB - Developmental dyslexia is an unexplained inability to acquire accurate or fluent reading that affects approximately 5-17% of children. Dyslexia is associated with structural and functional alterations in various brain regions that support reading. Neuroimaging studies in infants and pre-reading children suggest that these alterations predate reading instruction and reading failure, supporting the hypothesis that variant function in dyslexia susceptibility genes lead to atypical neural migration and/or axonal growth during early, most likely in utero, brain development. Yet, dyslexia is typically not diagnosed until a child has failed to learn to read as expected (usually in second grade or later). There is emerging evidence that neuroimaging measures, when combined with key behavioral measures, can enhance the accuracy of identification of dyslexia risk in pre-reading children but its sensitivity, specificity, and cost-efficiency is still unclear. Early identification of dyslexia risk carries important implications for dyslexia remediation and the amelioration of the psychosocial consequences commonly associated with reading failure. PMID- 26836232 TI - Kurt G. Hofer 1939-2015. PMID- 26836231 TI - Investigating the Radioresistant Properties of Lung Cancer Stem Cells in the Context of the Tumor Microenvironment. AB - Lung cancer is the most common cause of cancer-related deaths worldwide and non small cell lung cancer (NSCLC) accounts for ~85% of all lung cancer. While recent research has shown that cancer stem cells (CSC) exhibit radioresistant and chemoresistant properties, current cancer therapy targets the bulk of the tumor burden without accounting for the CSC and the contribution of the tumor microenvironment. CSC interaction with the stroma enhances NSCLC survival, thus limiting the efficacy of treatment. The aim of this study was to elucidate the role of CSC and the microenvironment in conferring radio- or chemoresistance in an in vitro tumor model for NSCLC. The novel in vitro three-dimensional (3D) NSCLC model of color-coded tumor tissue analogs (TTA) that we have developed is comprised of human lung adenocarcinoma cells, fibroblasts, endothelial cells and NSCLC cancer stem cells maintained in low oxygen conditions (5% O2) to recapitulate the physiologic conditions in tumors. Using this model, we demonstrate that a single 5 Gy radiation dose does not inhibit growth of TTA containing CSC and results in elevated expression of cytokines (TGF-alpha, RANTES, ENA-78) and factors (vimentin, MMP and TIMP), indicative of an invasive and aggressive phenotype. However, combined treatment of single dose or fractionated doses with cisplatin was found to either attenuate or decrease the proliferative effect that radiation exposure alone had on TTA containing CSC maintained in hypoxic conditions. In summary, we utilized a 3D NSCLC model, which had characteristics of the tumor microenvironment and tumor cell heterogeneity, to elucidate the multifactorial nature of radioresistance in tumors. PMID- 26836233 TI - Disorganized attachment in young adulthood as a partial mediator of relations between severity of childhood abuse and dissociation. AB - Disorganized attachment has been proposed as a mediating mechanism in the relation between childhood abuse and dissociation. However, support for mediation has been mixed when interview or self-report measures of attachment have been used. In the current work, relations among severity of abuse, attachment disorganization, and dissociation were assessed in young adulthood using both interview and interaction-based measures of attachment. A total of 112 low-income young adults were assessed for socioeconomic stresses, abusive experiences in childhood, and attachment disorganization at age 20. Attachment disorganization was assessed with the Adult Attachment Interview, coded independently for Unresolved states of mind and for Hostile-Helpless states of mind. Attachment disorganization was also measured using a newly validated assessment of young adult-parent interaction during a conflict discussion. Mediation analyses revealed that the link between childhood abuse and dissociation was partially explained by disturbances in young adult-parent interaction. Narrative disturbances on the Adult Attachment Interview were related to abuse and to dissociation but did not mediate the link between the two. Results are discussed in relation to the role of parent-child communication processes in pathways to dissociation. PMID- 26836234 TI - Repeated high-dose (5 * 10(8) TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits. AB - Concern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5*10(8) TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1*10(8) TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5*10(8) TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE vaccinated rabbits only. PMID- 26836235 TI - The inhibitory effect of soybean and soybean isoflavone diets on 2,4 dinitrofluorobenzene-induced contact hypersensitivity in mice. AB - Murine contact hypersensitivity (CHS) is one of the most frequently used animal models of human allergic contact dermatitis. We investigated the inhibitory effects of soybean and soy isoflavone (SI) diets on 2,4-dinitrofluorobenzene- (DNFB) induced CHS in mice. The DNFB-induced ear swelling was inhibited in the soy- and SI-treated groups. Histopathological investigations revealed that oral feeding of soybean and SI attenuated ear tissue edema and reduced the number of Gr-1(+) cell infiltrations into ear tissues. DNA microarray analysis showed that the expression of Ccl24, Xcl1, Ifng, and Ccl17 in the ear tissues was lower in the soy-treated mice than in the positive controls. In addition, CCL24 mRNA and protein expression in the ear tissues were more highly suppressed in the soy- and SI-treated groups. These results suggest that soybean and SI consumption downregulated the gene and protein expression of CCL24, thereby affording protection against CHS in mice. PMID- 26836236 TI - I Knew I Would Be Safer. Experiences of Kenyan HIV Serodiscordant Couples Soon After Pre-Exposure Prophylaxis (PrEP) Initiation. AB - Pre-exposure prophylaxis (PrEP) for HIV-uninfected persons is highly efficacious for HIV prevention. Understanding how people at risk for HIV will use PrEP is important to inform PrEP scale-up and implementation. We used qualitative methods to gather insights into couples' early experiences with PrEP use within the Partners Demonstration Project, an open-label implementation study evaluating integrated delivery of PrEP and antiretroviral therapy (ART). PrEP is offered to HIV uninfected partners until the HIV-infected partner initiates and sustains ART use (i.e., PrEP as a "bridge" to ART initiation and viral suppression). From August 2013 to March 2014 we conducted 20 in-depth dyadic interviews (n = 40) with heterosexual HIV serodiscordant couples participating at the Thika, Kenya study site, exploring how couples make decisions about using PrEP for HIV prevention. We developed and applied deductive and inductive codes to identify key themes related to experiences of PrEP initiation and use of time-limited PrEP. Couples reported that PrEP offered them an additional strategy to reduce the risk of HIV transmission, meet their fertility desires, and cope with HIV serodiscordance. Remaining HIV negative at follow-up visits reinforced couples' decisions and motivated continued adherence to PrEP. In addition, confidence in their provider's advice and client-friendly services were critical to their decisions to initiate and continue use of PrEP. Strategies for wide-scale PrEP delivery for HIV serodiscordant couples in low resource settings may include building capacity of health providers to counsel on PrEP adoption while addressing couples' concerns and barriers to adoption and continued use. PMID- 26836238 TI - Correction. PMID- 26836237 TI - Systematic Assessment of Linkage to Care for Persons with HIV Released from Corrections Facilities Using Existing Datasets. AB - Populations in corrections continue to have high prevalence of HIV. Expanded testing and treatment programs allow persons to be identified and stabilized on treatment while incarcerated. However, these gains and frequently lost on reentry. Systemic frameworks are needed to monitor linkage to care to guide programs supporting linkage to care. To assess the adequacy of linkage to care on reentry, incarceration data from the National Corrections Reporting Program and data from the Ryan White Services Report from 2010 to 2012 were linked using an encrypted client identification (eUCI). Time from release to the first visit and presence of detectable HIV RNA at linkage were assessed. Multivariate survival analyses were performed to identify associations between patient characteristics and time to linkage. Among those linking, only 43% in Rhode Island and 49% in North Carolina linked within 90 days, and 33% in both states had detectable viremia at the first visit. Those not previously in care and with shorter incarceration experiences longer linkage times. Persons identified as black, had median times greater than 1 year. Using existing datasets, significant gaps in linkage to care for persons with HIV on release from corrections were demonstrated in Rhode Island and North Carolina. Systemically implementing this monitoring to evaluate changes over time would provide important information to support interventions to improve linkage in high-risk populations. Using national datasets for both corrections and clinical data, this framework equally could be used to evaluate experiences of persons with HIV linking to care on release from corrections facilities nationwide. PMID- 26836239 TI - sCD48 is anti-inflammatory in Staphylococcus aureus Enterotoxin B-induced eosinophilic inflammation. AB - BACKGROUND: Staphylococcus aureus, one of the most important pathogens, is heavily associated with allergy. S. aureus and its toxins interact with eosinophils through CD48, a GPI-anchored receptor important in allergy mainly as expressed by the eosinophils (mCD48). CD48 can exist in a soluble form (sCD48). Our aim was to investigate SEB-induced regulation of eosinophil CD48 and the possible formation and role of sCD48 in SEB-mediated eosinophil activation in vitro and in vivo. METHODS: Human peripheral blood eosinophils were activated by SEB with or without inhibitors for phospholipases (PL) (-C or -D), or cycloheximide, or brefeldin A. We evaluated eosinophil activation (CD11b expression or EPO/IL-8 release), mCD48 (flow cytometry), sCD48 (ELISA), SEB binding to sCD48 (ELISA), and chemotaxis toward SEB. C57BL/6 mice were pre injected (ip.) with sCD48, and then, peritonitis was induced by SEB injection; peritoneal lavages were collected after 48 h and analyzed by flow cytometry and ELISA. RESULTS: SEB-activated human eosinophils formed sCD48, directly correlating with CD11b expression, through cell-associated PL-C and -D. mCD48 remained stable due to up-regulation in CD48 transcription and cellular trafficking. sCD48 bound to SEB and down-regulated SEB stimulatory effects on eosinophils as assessed by EPO and IL-8 release and eosinophil chemotaxis toward SEB. sCD48 showed anti-inflammatory activity in a SEB-induced mouse peritonitis model. CONCLUSIONS: SEB regulates CD48 dynamics on eosinophils. Our data indicate sCD48 as a SEB-induced 'decoy' receptor derived from eosinophil and therefore as a potential anti-inflammatory tool in S. aureus-induced eosinophil inflammation often associated with allergy. PMID- 26836240 TI - Naringenin ameliorates skin inflammation and accelerates phenotypic reprogramming from M1 to M2 macrophage polarization in atopic dermatitis NC/Nga mouse model. PMID- 26836241 TI - A review of the quality of life following pulsed dye laser treatment for erythemotelangiectatic rosacea. AB - Rosacea is a chronic condition, affecting up to 10% of the population. It has a negative impact on patients' quality of life (QOL), leading to loss of self confidence, emotional distress and withdrawal from normal societal interactions. Erythemotelangiectatic (ET) rosacea is a frequent reason for consultation and difficult to treat, as vascular signs such as flushing, erythema and telangiectasia often persist despite medical therapy. Several studies have demonstrated objective improvements in vascular signs following pulsed dye laser (PDL) treatment, but very few have investigated improvement in QOL. We reviewed the current literature to find evidence for the effect of PDL on QOL in ET rosacea. PMID- 26836242 TI - Development of a systematic computer vision-based method to analyse and compare images of false identity documents for forensic intelligence purposes-Part I: Acquisition, calibration and validation issues. AB - Following their detection and seizure by police and border guard authorities, false identity and travel documents are usually scanned, producing digital images. This research investigates the potential of these images to classify false identity documents, highlight links between documents produced by a same modus operandi or same source, and thus support forensic intelligence efforts. Inspired by previous research work about digital images of Ecstasy tablets, a systematic and complete method has been developed to acquire, collect, process and compare images of false identity documents. This first part of the article highlights the critical steps of the method and the development of a prototype that processes regions of interest extracted from images. Acquisition conditions have been fine-tuned in order to optimise reproducibility and comparability of images. Different filters and comparison metrics have been evaluated and the performance of the method has been assessed using two calibration and validation sets of documents, made up of 101 Italian driving licenses and 96 Portuguese passports seized in Switzerland, among which some were known to come from common sources. Results indicate that the use of Hue and Edge filters or their combination to extract profiles from images, and then the comparison of profiles with a Canberra distance-based metric provides the most accurate classification of documents. The method appears also to be quick, efficient and inexpensive. It can be easily operated from remote locations and shared amongst different organisations, which makes it very convenient for future operational applications. The method could serve as a first fast triage method that may help target more resource-intensive profiling methods (based on a visual, physical or chemical examination of documents for instance). Its contribution to forensic intelligence and its application to several sets of false identity documents seized by police and border guards will be developed in a forthcoming article (part II). PMID- 26836243 TI - Contact between traps and surfaces during contact sampling of explosives in security settings. AB - Realistic descriptions of interfacial contact between rough, deformable surfaces under load are difficult to obtain; however, this contact is of great import in a wide range of applications. Here, we detail, through experiment and computational simulation, the interfacial contact between four common traps and five commonly investigated surfaces encountered in explosives detection applications associated with airport security. The Young's modulus and hardness of four traps and seven substrates were measured using nanoindentation. These properties determine how deformation occurs when traps are applied for contact sampling of explosives. The nanoindentation data were analyzed using the Oliver-Pharr method, and an indenter area function was created using silicon and gold as the reference materials. The Young's moduli of the traps ranged from 0.2 to 8 GPa, while those of the surfaces ranged from 0.5 to 4 GPa. The hardness values of the traps ranged from 0.005 to 0.22 GPa, while those of the surfaces ranged from 0.02 to 0.2 GPa. For each of 20 scenarios (4 traps, 5 surfaces), six contact simulations were performed. In these contact simulations, the Greenwood-Willliamson microcontact model was used to represent the behavior of the asperities on the traps, while the Timoshenko Beam model was used to describe the macroscopic behavior of the bulk trap materials spanning the space between asperities. This combination of feature- and trap scale modeling provides a more realistic description of the interfacial contact than either model applied individually. The calculated distributions of separation distances between the traps and surfaces when the traps were contacted with the surfaces under a normal load were compared to estimate the relative effectiveness of the traps at interrogating the topography of the surfaces. This method is proposed as a tool to guide the development of trap materials for surface sampling and surface cleaning applications. PMID- 26836244 TI - Plasma fibrin clot properties in postmenopausal women: effects of hormone therapy. AB - OBJECTIVE: Postmenopausal women are at risk of thromboembolic events. It is unclear whether menopause alters fibrin clot properties. The aim of our study was to assess the effects of menopause and hormone therapy on clot characteristics. METHODS: Ex vivo plasma clot permeability, turbidity, and susceptibility to lysis were determined in 70 premenopausal and 70 postmenopausal women (a case-control study). From the postmenopausal group, 30 women were randomly assigned (1:1) to a 24-week oral or transdermal treatment with 17beta-estradiol, combined with norethisterone acetate (2 mg + 1 mg/d or 0.05 mg + 5 mg/d, respectively). RESULTS: Compared with premenopausal women (aged 29.2 +/- 2.60 y), postmenopausal women (aged 49.7 +/- 3.4 y; P = 0.009) were characterized by higher fibrinogen levels (by 36.8%), lower C-reactive protein levels (by 36.9%), and lower clot permeability (by 10.5%); also after adjustment for fibrinogen (all P < 0.05), with no difference in turbidimetric or fibrinolytic variables. Estrogen plus progestogen therapy led to higher maximal absorbency of fibrin gels by 6.0% (P < 0.05), whereas all other fibrin variables remained unchanged. Compared with transdermal hormone therapy, 24-week oral therapy was associated with higher absorbency of plasma clots by 16% (P < 0.05), without any other changes in fibrin characteristics. CONCLUSIONS: Menopause age is associated with the formation of denser fibrin clots. Estrogen plus progestogen therapy has a minor effect on plasma fibrin properties, but leads to the formation of thicker and more branched fibrin fibers, particularly during oral administration. PMID- 26836246 TI - Injectable biomaterials: a perspective on the next wave of injectable therapeutics. AB - We are experiencing a new wave of injectable therapeutics (namely/injectable biomaterials) to complement injectable drugs and injectable biologics, and to serve as the basis for injectable combinatorial therapeutics. Injectable biomaterials contribute to the treatment of the fluid-filled defects which often result from disease and injury, by providing the missing physical framework (i.e. the stroma). However, while injectable matrices may be necessary for the successful treatment of certain lesions, they will not likely be sufficient. Chemoattractants for select endogenous cells, or cells themselves, may need to be incorporated into the matrix prior to its injection to ensure the necessary cellular repopulation of the cavitary defect. These agents and others (drugs and biologics) delivered by the matrix represent the new category of injectable combinatorial therapeutics. PMID- 26836245 TI - A randomized, double-blind, placebo-controlled phase 2 pilot trial evaluating a novel, vaginal softgel capsule containing solubilized estradiol. AB - OBJECTIVE: The aim of the study was to evaluate the safety and efficacy of vaginal estradiol (E2) softgel capsules for moderate-to-severe symptoms of vulvar and vaginal atrophy (VVA). Previous phase 1 studies showed lower systemic estrogen concentrations with this softgel capsule compared with an approved low dose vaginal E2 tablet. METHODS: In this randomized, double-blind, placebo controlled phase 2 study, 50 postmenopausal women (aged 40-75 y) with at least1 moderate-to-severe VVA symptom received 10 MUg vaginal E2 softgel capsules or placebo daily for 14 days. Changes from baseline in vaginal maturation index, investigator's assessment of vaginal mucosa (secretions, epithelial integrity, epithelial surface thickness, color), vaginal pH, and most bothersome symptom were assessed. Adverse events were evaluated. RESULTS: Compared with placebo, the percentage of superficial (35.2 percentage points [pp] vs 8.75 pp; P = 0.0002) and intermediate (18.7 pp vs -3.54 pp; P = 0.0017) cells increased from baseline significantly more with vaginal E2 capsules, and parabasal cells decreased significantly more (-54.4 pp vs -4.80 pp; P < 0.0001). Vaginal pH decreased significantly more with vaginal E2 capsules (-0.974 vs -0.339; P = 0.0002). Decreases in severity of atrophic effects on vaginal epithelial integrity (-0.342 vs 0.176; P = 0.0001) and secretions (-0.643 vs -0.274; P = 0.0401) were significantly greater with vaginal E2 capsules vs placebo. There was no statistical difference in most bothersome symptom severity change from baseline. No serious adverse events were reported. CONCLUSIONS: Vaginal E2 softgel capsules are a safe, effective, local treatment option for postmenopausal women with moderate-to-severe VVA, with lower systemic estrogen absorption than currently available intravaginal treatments. PMID- 26836247 TI - A National Description of Violence toward Emergency Medical Services Personnel. AB - INTRODUCTION: EMS personnel often work in unpredictable environments and are at high risk for sustaining occupational injuries. One potential source of injury that is of growing concern is violence toward EMS personnel. OBJECTIVE: To describe the prevalence of violence directed at EMS personnel by type and source, and to identify characteristics associated with experiencing violence. METHODS: The 2013 Longitudinal EMT Attributes and Demographics Study contained 14 items assessing violence experienced in the past 12 months. Violence was categorized by type (physical or verbal) and by source (the patient or a patient's family member or bystander). EMS personnel characteristics included sex, age, race, marital status, certification level, firefighter, volunteerism, agency type, and community size. Descriptive and comparative analyses were performed on personnel whose primary role was providing patient care. Multivariable logistic regression modelling was used to assess associations between provider characteristics and experiencing violence. RESULTS: A total of 2,515/4,238 (59.3%) responses were received and 1,789 met inclusion criteria. Over two-thirds (69.0%) experienced at least one form of violence in the past 12 months. Verbal violence was more prevalent than physical (67.0% vs. 43.6%). Using multivariable logistic regression to control for other demographic and employment characteristics, paramedics had nearly triple the odds of experiencing physical (OR = 2.67, 95% CI = 2.06-3.46) and verbal (OR = 2.63, 95% CI = 1.99-3.46) violence as EMTs. Urban personnel had increased odds of experiencing physical (OR = 1.53, 95% CI = 1.21 1.93) and verbal violence (OR = 1.32, 95% CI = 1.02-1.71). Each additional weekly transport increased the odds of experiencing physical (OR = 1.04, 95% CI = 1.03 1.05) and verbal (OR = 1.04, 95% CI = 1.03-1.06) violence by 4%. Those who were volunteers at their main EMS jobs had decreased odds of experiencing physical (OR = 0.68, 95% CI = 0.50-0.92) and verbal (OR = 0.59, 95% CI = 0.44-0.78) violence. CONCLUSIONS: Over two-thirds of EMS personnel experienced at least one form of violence in the last 12 months. Demographic and employment characteristics associated with experiencing violence were identified. Our findings may be used in education initiatives to raise awareness of the high prevalence of violence toward EMS personnel and factors associated with experiencing violence. PMID- 26836249 TI - Li2S Film Formation on Lithium Anode Surface of Li-S batteries. AB - The precipitation of lithium sulfide (Li2S) on the Li metal anode surface adversely impacts the performance of lithium-sulfur (Li-S) batteries. In this study, a first-principles approach including density functional theory (DFT) and ab initio molecular dynamics (AIMD) simulations is employed to theoretically elucidate the Li2S/Li metal surface interactions and the nucleation and growth of a Li2S film on the anode surface due to long-chain polysulfide decomposition during battery operation. DFT analyses of the energetic properties and electronic structures demonstrate that a single molecule adsorption on Li surface releases energy forming chemical bonds between the S atoms and Li atoms from the anode surface. Reaction pathways of the Li2S film formation on Li metal surfaces are investigated based on DFT calculations. It is found that a distorted Li2S (111) plane forms on a Li(110) surface and a perfect Li2S (111) plane forms on a Li(111) surface. The total energy of the system decreases along the reaction pathway; hence Li2S film formation on the Li anode surface is thermodynamically favorable. The calculated difference charge density of the Li2S film/Li surface suggests that the precipitated film would interact with the Li anode via strong chemical bonds. AIMD simulations reveal the role of the anode surface structure and the origin of the Li2S formation via decomposition of Li2S8 polysulfide species formed at the cathode side and dissolved in the electrolyte medium in which they travel to the anode side during battery cycling. PMID- 26836248 TI - The effect of intravitreal injection of vehicle solutions on form deprivation myopia in tree shrews. AB - lntravitreal injection of substances dissolved in a vehicle solution is a common tool used to assess retinal function. We examined the effect of injection procedures (three groups) and vehicle solutions (four groups) on the development of form deprivation myopia (FDM) in juvenile tree shrews, mammals closely related to primates, starting at 24 days of visual experience (about 45 days of age). In seven groups (n = 7 per group), the myopia produced by monocular form deprivation (FD) was measured daily for 12 days during an 11-day treatment period. The FD eye was randomly selected; the contralateral eye served as an untreated control. The refractive state of both eyes was measured daily, starting just before FD began (day 1); axial component dimensions were measured on day 1 and after eleven days of treatment (day 12). Procedure groups: the myopia (treated eye - control eye refraction) in the FD group was the reference. The sham group only underwent brief daily anesthesia and opening of the conjunctiva to expose the sclera. The puncture group, in addition, had a pipette inserted daily into the vitreous. In four vehicle groups, 5 MUL of vehicle was injected daily. The NaCl group received 0.85% NaCl. In the NaCl + ascorbic acid group, 1 mg/mL of ascorbic acid was added. The water group received sterile water. The water + ascorbic acid group received water with ascorbic acid (1 mg/mL). We found that the procedures associated with intravitreal injections (anesthesia, opening of the conjunctiva, and puncture of the sclera) did not significantly affect the development of FDM. However, injecting 5 MUL of any of the four vehicle solutions slowed the development of FDM. NaCl had a small effect; myopia development in the last 6 days (-0.15 +/- 0.08 D/day) was significantly less than in the FD group (-0.55 +/ 0.06 D/day). NaCl + Ascorbic acid further slowed the development of FDM on several treatment days. H2O (-0.09 +/- 0.05 D/day) and H2O + ascorbic acid (-0.08 +/- 0.05 D/day) both almost completely blocked myopia development. The treated eye vitreous chamber elongation, compared with the control eye, in all groups was consistent with the amount of myopia. When FD continued (days 12-16) without injections in the water and water + ascorbic acid groups, the rate of myopia development quickly increased. Thus, it appears the vehicles affected retinal signaling rather than causing damage. The effect of water and water + ascorbic acid may be due to reduced osmolality or ionic concentration near the tip of the injection pipette. The effect of ascorbic acid, compared to NaCl alone, may be due to its reported dopaminergic activity. PMID- 26836251 TI - Correlation and Prediction of Redox Potentials of Hydrogen Evolution Mononuclear Cobalt Catalysts via Molecular Electrostatic Potential: A DFT Study. AB - Reduction potentials (E(0)) of six mononuclear cobalt catalysts (1-6) for hydrogen evolution reaction and electron donating/withdrawing effect of nine X substituents on their macrocyclic ligand are reported at solvation effect included B3P86/6-311+G** level of density functional theory. The electrostatic potential at the Co nucleus (V(Co)) is found to be a powerful descriptor of the electronic effect experienced by Co from the ligand environment. The V(Co) values vary substantially with respect to the nature of macrocycle, type of apical ligands, nature of substituent and oxidation state of the metal center. Most importantly, V(Co) values of both the oxidized and reduced states of all the six complexes show strong linear correlation with E(0). The correlation plots between V(Co) and E(0) provide an easy-to-interpret graphical interpretation and quantification of the effect of ligand environment on the reduction potential. Further, on the basis of a correlation between the relative V(Co) and relative E(0) values of a catalyst with respect to the CF3-substituted reference system, the E(0) of any X-substituted 1-6 complexes is predicted. PMID- 26836250 TI - Maternal diabetes promotes mTORC1 downstream signalling in rabbit preimplantation embryos. AB - The mammalian target of rapamycin complex 1 (mTORC1) is known to be a central cellular nutrient sensor and master regulator of protein metabolism; therefore, it is indispensable for normal embryonic development. We showed previously in a diabetic pregnancy that embryonic mTORC1 phosphorylation is increased in case of maternal hyperglycaemia and hypoinsulinaemia. Further, the preimplantation embryo is exposed to increased L-leucine levels during a diabetic pregnancy. To understand how mTOR signalling is regulated in preimplantation embryos, we examined consequences of L-leucine and glucose stimulation on mTORC1 signalling and downstream targets in in vitro cultured preimplantation rabbit blastocysts and in vivo. High levels of L-leucine and glucose lead to higher phosphorylation of mTORC1 and its downstream target ribosomal S6 kinase 1 (S6K1) in these embryos. Further, L-leucine supplementation resulted in higher embryonic expression of genes involved in cell cycle (cyclin D1; CCND1), translation initiation (eukaryotic translation initiation factor 4E; EIF4E), amino acid transport (large neutral amino acid transporter 2; Lat2: gene SLC7A8) and proliferation (proliferating cell nuclear antigen; PCNA) in a mTORC1-dependent manner. Phosphorylation of S6K1 and expression patterns of CCND1 and EIF4E were increased in embryos from diabetic rabbits, while the expression of proliferation marker PCNA was decreased. In these embryos, protein synthesis was increased and autophagic activity was decreased. We conclude that mammalian preimplantation embryos sense changes in nutrient supply via mTORC1 signalling. Therefore, mTORC1 may be a decisive mediator of metabolic programming in a diabetic pregnancy. PMID- 26836252 TI - The fungal community changes over time in developing wheat heads. AB - Under normal conditions, wheat is colonized by a multitude of fungi that can have beneficial or adverse effects on plant growth and yield. To study the effect of spraying wheat heads with fungicides on the fungal community from emergence to harvest we applied an amplicon sequencing approach on single wheat heads. The climatic data showed that the spring of 2014 was very dry and without precipitation in the two weeks around flowering. An initial quantitative PCR showed that the total amount of fungal DNA increased during the entire period, without significant difference between sprayed and control wheat heads. Amplicon sequencing of the internal transcribed spacer 2 (ITS2) region showed that operational taxonomic units (OTUs) identified as Sporobolomyces roseus dominated in the first weeks, whereas Alternaria infectoria OTUs dominated in the last weeks before harvest. The only observed significant difference was that the control wheat heads contained more of the powdery mildew causing Blumeria graminis f. sp. tritici OTUs compared with the sprayed wheat heads. The dry conditions around flowering most likely also had an effect on Fusarium head blight infection as Fusarium OTUs were only sporadically encountered. Analyses of secondary metabolites produced by Fusarium and Alternaria in the wheat heads confirmed the observations from the amplicon sequencing. Enniatin B was the most frequent contaminant present in four sprayed (49-538 ng/g) and three control (56 355 ng/g) wheat heads. The A. infectoria secondary metabolites infectopyrone and 4Z-infectopyrone were however consistently observed in all samples collected the last five weeks before harvest. PMID- 26836254 TI - Old habits die hard--a reply to Adam La Caze. PMID- 26836253 TI - Empirical evaluation demonstrated importance of validating biomarkers for early detection of cancer in screening settings to limit the number of false-positive findings. AB - OBJECTIVES: Search for biomarkers for early detection of cancer is a very active area of research, but most studies are done in clinical rather than screening settings. We aimed to empirically evaluate the role of study setting for early detection marker identification and validation. STUDY DESIGN AND SETTING: A panel of 92 candidate cancer protein markers was measured in 35 clinically identified colorectal cancer patients and 35 colorectal cancer patients identified at screening colonoscopy. For each case group, we selected 38 controls without colorectal neoplasms at screening colonoscopy. Single-, two- and three-marker combinations discriminating cases and controls were identified in each setting and subsequently validated in the alternative setting. RESULTS: In all scenarios, a higher number of predictive biomarkers were initially detected in the clinical setting, but a substantially lower proportion of identified biomarkers could subsequently be confirmed in the screening setting. Confirmation rates were 50.0%, 84.5%, and 74.2% for one-, two-, and three-marker algorithms identified in the screening setting and were 42.9%, 18.6%, and 25.7% for algorithms identified in the clinical setting. CONCLUSION: Validation of early detection markers of cancer in a true screening setting is important to limit the number of false positive findings. PMID- 26836255 TI - Poor record linkage sensitivity biased outcomes in a linked cohort analysis. AB - OBJECTIVES: To examine the validity of deterministic compared to probabilistic record linkage in the ascertainment of hospitalizations in two linked cohorts. STUDY DESIGN AND SETTING: HIV-negative (HIV-ve) (n = 1,325) and HIV-positive (HIV+ve) gay and bisexual men (n = 557) recruited in Sydney, Australia, were probabilistically and deterministically linked to a statewide hospital registry (July 2000-June 2012). RESULTS: Using probabilistic linkage as the reference standard, deterministic linkage had higher specificity but much lower sensitivity [34.67% (95% confidence interval: 33.44, 35.92)]. A disproportionate number of links missed were individuals with poorer socioeconomic and health indicators, including HIV status. Risk of hospitalization compared to the general male population [HIV+ve standardized incidence ratio (SIR) = 1.45 (1.33-1.59); HIV-ve SIR = 0.72 (0.67-0.78)] was significantly underestimated when deterministic linkage was used [HIV+ve SIR = 0.46 (0.37-0.58); HIV-ve SIR = 0.29 (0.24-0.35)]. The impact of linkage strategy on the calculation of incidence rate ratios (IRRs) was less, but a greater discrepancy in IRRs was seen for diagnostic categories where event rates were low or where the sensitivity of the deterministic linkage was differential between the two cohorts. CONCLUSION: Linkage without proven high sensitivity and specificity should be carefully considered. In circumstances of undetermined sensitivity, SIRs should not be calculated as the extent of underestimation is unknown. The comparison of linked events within or between cohorts is more robust to linkage misclassification; however, selection bias does affect estimates and should be considered before linkage. PMID- 26836256 TI - Submicrometer Hollow Bioglass Cones Deposited by Radio Frequency Magnetron Sputtering: Formation Mechanism, Properties, and Prospective Biomedical Applications. AB - This work reports on the unprecedented magnetron sputtering deposition of submicrometric hollow cones of bioactive glass at low temperature in the absence of any template or catalyst. The influence of sputtering conditions on the formation and development of bioglass cones was studied. It was shown that larger populations of well-developed cones could be achieved by increasing the argon sputtering pressure. A mechanism describing the growth of bioglass hollow cones is presented, offering the links for process control and reproducibility of the cone features. The composition, structure, and morphology of the as-synthesized hollow cones were investigated by energy dispersive spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR), grazing incidence geometry X-ray diffraction (GIXRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM)-selected area electron diffraction (SAED). The in vitro biological performance, assessed by degradation tests (ISO 10993-14) and cytocompatibility assays (ISO 10993-5) in endothelial cell cultures, was excellent. This allied with resorbability and the unique morphological features make the submicrometer hollow cones interesting candidate material devices for focal transitory permeabilization of the blood-brain barrier in the treatment of carcinoma and neurodegenerative disorders. PMID- 26836258 TI - Amorphous Protic Ionic Systems as Promising Active Pharmaceutical Ingredients: The Case of the Sumatriptan Succinate Drug. AB - In this article, we highlight the benefits coming from the application of amorphous protic ionic systems as active pharmaceutical ingredients (APIs). Using the case of the sumatriptan (STR) drug, we show that the conversion of nonionic API to partially ionized amorphous protic succinate salt (STR SUCC) brings a substantial improvement in apparent solubility. Since in general the disordered systems reveal a tendency to self-arrangement during storage, the dominant part of this article is dedicated to the physical stability issue of sumatriptan and its ionic counterpart. To recognize the crystallization tendency of the studied systems, the calorimetric measurements were performed. Additionally, the role of ion dynamics in spontaneous nucleation of amorphous sumatriptan succinate is discussed. The differential scanning calorimetry analysis of ionic and nonionic sumatriptan reveals many similarities in thermal properties of these APIs as well as distinct differences in their resistance against crystallization in the supercooled liquid state. To determine the long-term physical stability of STR SUCC at room temperature conditions, the time scale of structural relaxation below their glass transition temperatures is estimated. We show that in contrast to nonionic materials, taualpha predictions of STR SUCC are much more complex and require aging experiments. PMID- 26836259 TI - OCULAR MANIFESTATIONS OF PRIMARY MYELOFIBROSIS. AB - PURPOSE: To report ocular manifestations of idiopathic primary myelofibrosis in a patient with relapsed primary myelofibrosis. METHODS: Observational case report. RESULTS: A 57-year-old African American male with history of primary myelofibrosis, diagnosed by bone marrow aspirate and biopsy, believed to be in remission was referred to us for bilateral angle-closure glaucoma refractory to medical treatment and laser peripheral iridotomy. His fundus examination revealed serous retinal detachments, choroidal effusions, and Roth spots, and B-scan revealed his angle closure was due to annular anterior ciliochoroidal effusions. The patient was taken to surgery for a pars plana vitrectomy with radial sclerotomies performed to relieve the patient's eye pressure in the left eye. Cytologic analysis of the choroidal effusions revealed neutrophilic infiltrates with immature forms and erythroid precursors, suggesting a neoplastic infiltration from the patient's primary myelofibrosis. The patient's vision and ocular symptoms significantly improved after chemotherapy. Repeat bone marrow aspiration and biopsy confirmed the patient's primary myelofibrosis with no progression to acute leukemia despite his high leukocyte count. CONCLUSION: Neoplastic infiltration of primary idiopathic myelofibrosis into the eye and surrounding structures, which is scantly described in the current literature, may be an early sign of new onset or relapsing primary myelofibrosis. Chemotherapy can be very effective in the ultimate treatment and remission of these ocular symptoms. PMID- 26836257 TI - Molecular Mechanisms of Glutamine Synthetase Mutations that Lead to Clinically Relevant Pathologies. AB - Glutamine synthetase (GS) catalyzes ATP-dependent ligation of ammonia and glutamate to glutamine. Two mutations of human GS (R324C and R341C) were connected to congenital glutamine deficiency with severe brain malformations resulting in neonatal death. Another GS mutation (R324S) was identified in a neurologically compromised patient. However, the molecular mechanisms underlying the impairment of GS activity by these mutations have remained elusive. Molecular dynamics simulations, free energy calculations, and rigidity analyses suggest that all three mutations influence the first step of GS catalytic cycle. The R324S and R324C mutations deteriorate GS catalytic activity due to loss of direct interactions with ATP. As to R324S, indirect, water-mediated interactions reduce this effect, which may explain the suggested higher GS residual activity. The R341C mutation weakens ATP binding by destabilizing the interacting residue R340 in the apo state of GS. Additionally, the mutation is predicted to result in a significant destabilization of helix H8, which should negatively affect glutamate binding. This prediction was tested in HEK293 cells overexpressing GS by dot-blot analysis: Structural stability of H8 was impaired through mutation of amino acids interacting with R341, as indicated by a loss of masking of an epitope in the glutamate binding pocket for a monoclonal anti-GS antibody by L-methionine-S sulfoximine; in contrast, cells transfected with wild type GS showed the masking. Our analyses reveal complex molecular effects underlying impaired GS catalytic activity in three clinically relevant mutants. Our findings could stimulate the development of ATP binding-enhancing molecules by which the R324S mutant can be repaired extrinsically. PMID- 26836260 TI - Intermolecular Noncovalent Hydroxy-Directed Enantioselective Heck Desymmetrization of Cyclopentenol: Computationally Driven Synthesis of Highly Functionalized cis-4-Arylcyclopentenol Scaffolds. AB - New computationally driven protocols for the Heck desymmetrization of 3 cyclopenten-1-ol with aryldiazonium tetrafluoroborates were developed. These new conditions furnished remarkable product selectivity originating from a resident hydroxyl group and the critical choice of the reaction solvent. Mechanistic insights gleaned from theoretical calculations of the putative transition states predicted toluene as an adequate solvent choice to attain high enantioselectivity by strengthening the noncovalent interaction of the substrate hydroxyl group and the chiral cationic palladium catalyst. Laboratory experiments validated the theoretical predictions, and by employing 2% MeOH/toluene as solvent, the Heck Matsuda reaction provided exclusively the cis-4-arylcyclopentenols 3a-l in good to excellent yields in enantiomeric excesses up to 99%. The performance of the new PyOx ligand (S)-4-tert-butyl-2-(3,5-dichloropyridin-2-yl)-4,5-dihydrooxazole was also successfully evaluated in the Heck-Matsuda desymmetrization of 3 cyclopenten-1-ol. The synthetic potential of these highly functionalized cis-4 arylcyclopentenols is illustrated by a gold-catalyzed synthesis of cyclopenta[b]benzofuran skeletons. PMID- 26836262 TI - Sn4+ Ion Decorated Highly Conductive Ti3C2 MXene: Promising Lithium-Ion Anodes with Enhanced Volumetric Capacity and Cyclic Performance. AB - Two-dimensional transition metal carbide materials called MXenes show potential application for energy storage due to their remarkable electrical conductivity and low Li(+) diffusion barrier. However, the lower capacity of MXene anodes limits their further application in lithium-ion batteries. Herein, with inspiration from the unique metal ion uptake behavior of highly conductive Ti3C2 MXene, we overcome this impediment by fabricating Sn(4+) ion decorated Ti3C2 nanocomposites (PVP-Sn(IV)@Ti3C2) via a facile polyvinylpyrrolidone (PVP) assisted liquid-phase immersion process. An amorphous Sn(IV) nanocomplex, about 6 7 nm in lateral size, has been homogeneously anchored on the surface of alk-Ti3C2 matrix by ion-exchange and electrostatic interactions. In addition, XRD and TEM results demonstrate the successful insertion of Sn(4+) into the interlamination of an alkalization-intercalated Ti3C2 (alk-Ti3C2) matrix. Due to the possible "pillar effect" of Sn between layers of alk-Ti3C2 and the synergistic effect between the alk-Ti3C2 matrix and Sn, the nanocomposites exhibit a superior reversible volumetric capacity of 1375 mAh cm(-3) (635 mAh g(-1)) at 216.5 mA cm( 3) (100 mA g(-1)), which is significantly higher than that of a graphite electrode (550 mAh cm(-3)), and show excellent cycling stability after 50 cycles. Even at a high current density of 6495 mA cm(-3) (3 A g(-1)), these nanocomposites retain a stable specific capacity of 504.5 mAh cm(-3) (233 mAh g( 1)). These results demonstrate that PVP-Sn(IV)@Ti3C2 nanocomposites offer fascinating potential for high-performance lithium-ion batteries. PMID- 26836261 TI - Global biogeography of Prochlorococcus genome diversity in the surface ocean. AB - Prochlorococcus, the smallest known photosynthetic bacterium, is abundant in the ocean's surface layer despite large variation in environmental conditions. There are several genetically divergent lineages within Prochlorococcus and superimposed on this phylogenetic diversity is extensive gene gain and loss. The environmental role in shaping the global ocean distribution of genome diversity in Prochlorococcus is largely unknown, particularly in a framework that considers the vertical and lateral mechanisms of evolution. Here we show that Prochlorococcus field populations from a global circumnavigation harbor extensive genome diversity across the surface ocean, but this diversity is not randomly distributed. We observed a significant correspondence between phylogenetic and gene content diversity, including regional differences in both phylogenetic composition and gene content that were related to environmental factors. Several gene families were strongly associated with specific regions and environmental factors, including the identification of a set of genes related to lower nutrient and temperature regions. Metagenomic assemblies of natural Prochlorococcus genomes reinforced this association by providing linkage of genes across genomic backbones. Overall, our results show that the phylogeography in Prochlorococcus taxonomy is echoed in its genome content. Thus environmental variation shapes the functional capabilities and associated ecosystem role of the globally abundant Prochlorococcus. PMID- 26836264 TI - Effects of antipsychotics on insight in schizophrenia: results from independent samples of first-episode and acutely relapsed patients. AB - We aimed to investigate whether antipsychotics differentially impact insight and whether these effects appear because of improvement in psychopathological manifestation in 132 first-episode schizophrenia patients and 201 acutely relapsed schizophrenic patients, who were followed up for 12 weeks. Olanzapine and risperidone were administered to first-episode schizophrenia patients, whereas acutely relapsed schizophrenic patients were treated with olanzapine, perazine and ziprasidone. The Positive And Negative Syndrome Scale (PANSS) was used to assess psychopathology. Insight was assessed using the G12 item of PANSS. Unadjusted mixed-model regression analysis indicated a significant improvement in the PANSS G12 item score in both groups. There were no significant differences between distinct treatment subgroups of patients in terms of improvement in the PANSS G12 item score. After adjustment for the trajectories of changes in symptom dimensions, a decrease in the PANSS G12 item score was because of an improvement in positive, negative and excitement symptoms. A decrease in the PANSS G12 item score was also related to an increase in the severity of depressive symptomatology. Our results indicate that antipsychotics exert similar effects on insight in acute psychosis. These effects are likely because of an improvement in psychopathological manifestation. The improvement in insight might be related to the development of depressive symptoms. PMID- 26836266 TI - Synthesis of cis-[Cr(diimine)2(1-methylimidazole)2](3+) Complexes and an Investigation of Their Interaction with Mononucleotides and Polynucleotides. AB - A protocol is presented for the synthesis of chromium(III) complexes of the type cis-[Cr(diimine)2(1-methylimidazole)2](3+). These compounds exhibit large excited state oxidizing powers and strong luminescence in solution. Emission is quenched by added guanine, yielding rate constants that track the driving force for guanine oxidation. The cis-[Cr(TMP)(DPPZ)(1-MeImid)2](3+) species binds strongly to duplex DNA with a preference for AT base sites in the minor groove and may serve as a precursor for photoactivated DNA covalent adduct formation. PMID- 26836267 TI - Characteristics and Young's Modulus of Collagen Fibrils from Expanded Skin Using Anisotropic Controlled Rate Self-Inflating Tissue Expander. AB - Mechanical properties of expanded skin tissue are different from normal skin, which is dependent mainly on the structural and functional integrity of dermal collagen fibrils. In the present study, mechanical properties and surface topography of both expanded and nonexpanded skin collagen fibrils were evaluated. Anisotropic controlled rate self-inflating tissue expanders were placed beneath the skin of sheep's forelimbs. The tissue expanders gradually increased in height and reached equilibrium in 2 weeks. They were left in situ for another 2 weeks before explantation. Expanded and normal skin samples were surgically harvested from the sheep (n = 5). Young's modulus and surface topography of collagen fibrils were measured using an atomic force microscope. A surface topographic scan showed organized hierarchical structural levels: collagen molecules, fibrils and fibers. No significant difference was detected for the D-banding pattern: 63.5 +/- 2.6 nm (normal skin) and 63.7 +/- 2.7 nm (expanded skin). Fibrils from expanded tissues consisted of loosely packed collagen fibrils and the width of the fibrils was significantly narrower compared to those from normal skin: 153.9 +/- 25.3 and 106.7 +/- 28.5 nm, respectively. Young's modulus of the collagen fibrils in the expanded and normal skin was not statistically significant: 46.5 +/- 19.4 and 35.2 +/- 27.0 MPa, respectively. In conclusion, the anisotropic controlled rate self-inflating tissue expander produced a loosely packed collagen network and the fibrils exhibited similar D-banding characteristics as the control group in a sheep model. However, the fibrils from the expanded skin were significantly narrower. The stiffness of the fibrils from the expanded skin was higher but it was not statistically different. PMID- 26836265 TI - Association of Forced Vital Capacity with the Developmental Gene NCOR2. AB - BACKGROUND: Forced Vital Capacity (FVC) is an important predictor of all-cause mortality in the absence of chronic respiratory conditions. Epidemiological evidence highlights the role of early life factors on adult FVC, pointing to environmental exposures and genes affecting lung development as risk factors for low FVC later in life. Although highly heritable, a small number of genes have been found associated with FVC, and we aimed at identifying further genetic variants by focusing on lung development genes. METHODS: Per-allele effects of 24,728 SNPs in 403 genes involved in lung development were tested in 7,749 adults from three studies (NFBC1966, ECRHS, EGEA). The most significant SNP for the top 25 genes was followed-up in 46,103 adults (CHARGE and SpiroMeta consortia) and 5,062 children (ALSPAC). Associations were considered replicated if the replication p-value survived Bonferroni correction (p<0.002; 0.05/25), with a nominal p-value considered as suggestive evidence. For SNPs with evidence of replication, effects on the expression levels of nearby genes in lung tissue were tested in 1,111 lung samples (Lung eQTL consortium), with further functional investigation performed using public epigenomic profiling data (ENCODE). RESULTS: NCOR2-rs12708369 showed strong replication in children (p = 0.0002), with replication unavailable in adults due to low imputation quality. This intronic variant is in a strong transcriptional enhancer element in lung fibroblasts, but its eQTL effects could not be tested due to low imputation quality in the eQTL dataset. SERPINE2-rs6754561 replicated at nominal level in both adults (p = 0.036) and children (p = 0.045), while WNT16-rs2707469 replicated at nominal level only in adults (p = 0.026). The eQTL analyses showed association of WNT16 rs2707469 with expression levels of the nearby gene CPED1. We found no statistically significant eQTL effects for SERPINE2-rs6754561. CONCLUSIONS: We have identified a new gene, NCOR2, in the retinoic acid signalling pathway pointing to a role of vitamin A metabolism in the regulation of FVC. Our findings also support SERPINE2, a COPD gene with weak previous evidence of association with FVC, and suggest WNT16 as a further promising candidate. PMID- 26836268 TI - Docosahexaenoic Acid-Rich Fish Oil Supplementation Improves Body Composition without Influence of the PPARgamma Pro12Ala Polymorphism in Patients with Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. AB - BACKGROUND: The aims of this research were to investigate (1) the impact of docosahexaenoic acid (DHA)-rich fish oil supplementation on body composition, plasma adiponectin level, and peroxisome proliferator-activated receptor gamma (PPARgamma) gene expression, and (2) whether the effect of DHA-rich fish oil supplementation on the aforementioned variables is modulated by PPARgamma Pro12Ala polymorphism. METHODS: We genotyped PPARgamma Pro12Ala polymorphism in subjects with type 2 diabetes mellitus (T2DM). Ala carriers and non-Ala carriers were randomly assigned to DHA-rich fish oil or placebo intake for 8 weeks. RESULTS: Glycemic control was not affected by the intervention. The supplementation with DHA-rich fish oil decreased waist circumference (p < 0.001), body fat mass (p = 0.01), body fat percent (p = 0.04), and viscera fat rating (p = 0.02) as well as trunk fat mass (p = 0.04). Weight, body mass index, fat-free mass, adiponectin level, and PPARgamma gene expression changes showed no significant difference. No gene-diet interaction was found on body composition, adiponectin level, and PPARgamma gene expression. CONCLUSIONS: DHA-rich fish oil supplementation favorably modulated body composition in patients with T2DM and could be useful to reduce visceral obesity. However, the PPARgamma Pro12Ala polymorphism did not influence the changes in the desired variables. PMID- 26836269 TI - Disseminated intravascular coagulation with positive D-dimer: a controversial clinical feature in severe congenital factor XIII deficiency in southeast Iran. AB - Disseminated intravascular coagulation (DIC) is an extremely rare coagulopathy in the rare factor XIII (FXIII) deficiency. Compensated DIC occurs because of injuries that lead to systemic coagulation activation that is amplified by impaired fibrinolysis. This challenge translates into the widespread deposition of fibrin degradation products in the circulation. The aim of this study is to report three cases with severe FXIII deficiency who presented with DIC and positive D-dimer. Here we describe three patients affected by both FXIII deficiency and DIC; two girls aged 17 and 45 days and a 3.5-year-old boy. All patients had a positive family history for FXIII deficiency. Umbilical cord bleeding was the first presentation of FXIII deficiency in all of them, who presented also with ecchymosis; two of them had delayed wound bleeding. DIC occurred simultaneously with intracranial haemorrhage in two patients, whereas the third experienced DIC following extensive haematoma. D-dimer measured in all patients ranged between 5 and 20 MUg/ml, whereas fibrinogen degradation product was between 4 and 8 MUg/ml. PMID- 26836270 TI - Cytochrome P450 2C8*2 allele in Botswana: Human genetic diversity and public health implications. AB - Human cytochrome P450 2C8 is a highly polymorphic gene and shows variation according to ethnicity. The CYP2C8*2 is a slow drug metabolism allele and shows 10-24% frequency in Black populations. The objective of this study was to assess the prevalence of CYP2C8*2 allele in Botswana among the San (or Bushmen) and the Bantu ethnic groups. For that purpose we recruited 544 children of the two ethnicities in three districts of Botswana from primary schools, collected blood samples, extracted DNA and genotyped them through PCR-based restriction fragment length polymorphism analysis. The results demonstrated that in the San the prevalence of the CYP2C8*2 allele is significantly higher than among the Bantu related ethnic groups (17.5% and 8.5% for San and Bantu, respectively; P=0.00002). These findings support the evidence of a different genetic background of the San with respect to Bantu-related populations, and highlight a possible higher risk of longer drug clearance or poor level of activation of pro-drugs among the San group. PMID- 26836271 TI - Attenuation of a select agent-excluded Burkholderia pseudomallei capsule mutant in hamsters. AB - Burkholderia pseudomallei is a Tier 1 select agent and potential bioweapon. Given it is potential to cause a lethal respiratory disease, research with fully virulent B. pseudomallei is conducted in Biosafety Level 3 (BSL-3) laboratory spaces. The logistical, financial, and administrative burden of Tier 1 select agent BSL-3 research has created an interest in mitigating such burdens through the use of either attenuated B. pseudomallei strains at BSL-2, or research with surrogate species, such as Burkholderia thailandensis. Previously, attenuated B. pseudomallei auxotroph mutants (asd and purM) have been approved for exclusion from select agent requirements, allowing for in vitro studies to be conducted at BSL-2. Acapsular B. pseudomallei mutants are known to be strongly attenuated in a variety of animal models, and yet acapsular B. pseudomallei mutants do not require nutritional supplementation, and can be studied within cultured macrophages, performing phenotypically similarly to parent strains. We demonstrate that the loss of a 30.8 kb region of the wcb capsule operon allows for a dramatic >4.46 log attenuation in a hamster intraperitoneal infection model, and report that this strain, JW270, has met criteria for exclusion from select agent requirements. PMID- 26836272 TI - NMDA receptor antagonists attenuate the proconvulsant effect of juvenile social isolation in male mice. AB - Experiencing psychosocial stress in early life, such as social isolation stress (SIS), is known to have negative enduring effects on the development of the brain and behavior. In addition to anxiety and depressive-like behaviors, we previously showed that juvenile SIS increases susceptibility to pentylenetetrazole (PTZ) induced seizures in mice through enhancing the nitrergic system activity in the hippocampus. In this study, we investigated the possible involvement of N-methyl D-aspartate (NMDA) receptors in proconvulsant effects of juvenile SIS. Applying 4 weeks of SIS to juvenile male mice at postnatal day 21-23, we observed an increased susceptibility to PTZ as well as anxiety and depressive-like behaviors in adult mice. Intraperitoneal (i.p.) administration of NMDA receptor antagonists, MK-801 (0.05 mg/kg) and ketamine (0.5mg/kg), reversed the proconvulsant effects of SIS in Isolated (and not social) housed animals. Co administration of non-effective doses of nitric oxide synthase (NOS) inhibitors, 7NI (25mg/kg) and L-NAME (10mg/kg), with NMDA receptor antagonists, MK-801 (0.01 mg/kg) and ketamine (0.1mg/kg) attenuated the proconvulsant effects of juvenile SIS only in isolated housed mice. Also, using real time RT-PCR, we showed that hippocampal upregulation of NR2B subunit of NMDA receptor may play a critical role in proconvulsant effects of juvenile SIS by dysregulation of NMDA/NO pathway. In conclusion, results of present study revealed that experiencing SIS during adolescence predisposes the co-occurrence of seizure disorders with psychiatric comorbidities and also, alteration of NMDA receptor structure and function in hippocampus plays a role in proconvulsant effects of juvenile SIS through enhancing the NMDA/NO pathway. PMID- 26836273 TI - Sintering-Resistant Single-Site Nickel Catalyst Supported by Metal-Organic Framework. AB - Developing supported single-site catalysts is an important goal in heterogeneous catalysis since the well-defined active sites afford opportunities for detailed mechanistic studies, thereby facilitating the design of improved catalysts. We present herein a method for installing Ni ions uniformly and precisely on the node of a Zr-based metal-organic framework (MOF), NU-1000, in high density and large quantity (denoted as Ni-AIM) using atomic layer deposition (ALD) in a MOF (AIM). Ni-AIM is demonstrated to be an efficient gas-phase hydrogenation catalyst upon activation. The structure of the active sites in Ni-AIM is proposed, revealing its single-site nature. More importantly, due to the organic linker used to construct the MOF support, the Ni ions stay isolated throughout the hydrogenation catalysis, in accord with its long-term stability. A quantum chemical characterization of the catalyst and the catalytic process complements the experimental results. With validation of computational modeling protocols, we further targeted ethylene oligomerization catalysis by Ni-AIM guided by theoretical prediction. Given the generality of the AIM methodology, this emerging class of materials should prove ripe for the discovery of new catalysts for the transformation of volatile substrates. PMID- 26836274 TI - Towards breast tomography with synchrotron radiation at Elettra: first images. AB - The aim of the SYRMA-CT collaboration is to set-up the first clinical trial of phase-contrast breast CT with synchrotron radiation (SR). In order to combine high image quality and low delivered dose a number of innovative elements are merged: a CdTe single photon counting detector, state-of-the-art CT reconstruction and phase retrieval algorithms. To facilitate an accurate exam optimization, a Monte Carlo model was developed for dose calculation using GEANT4. In this study, high isotropic spatial resolution (120 MUm)(3) CT scans of objects with dimensions and attenuation similar to a human breast were acquired, delivering mean glandular doses in the range of those delivered in clinical breast CT (5-25 mGy). Due to the spatial coherence of the SR beam and the long distance between sample and detector, the images contain, not only absorption, but also phase information from the samples. The application of a phase-retrieval procedure increases the contrast-to-noise ratio of the tomographic images, while the contrast remains almost constant. After applying the simultaneous algebraic reconstruction technique to low-dose phase-retrieved data sets (about 5 mGy) with a reduced number of projections, the spatial resolution was found to be equal to filtered back projection utilizing a four fold higher dose, while the contrast-to noise ratio was reduced by 30%. These first results indicate the feasibility of clinical breast CT with SR. PMID- 26836275 TI - Eating disorders, gene-environment interactions and the epigenome: Roles of stress exposures and nutritional status. AB - Epigenetic mechanisms are believed to link environmental exposures to gene expression, and in so doing, to provide a physical basis for the activation, by life experiences, of mental-health problems. This paper provides a background to the hypothesis that epigenetic mechanisms link life stresses (perinatal, childhood and adult) and effects of malnutrition to the eating disorders (EDs). The paper reviews literature bearing upon the putative link between epigenetic factors and ED development, and examines ways in which epigenetic alterations could account for risk of eating disturbances and commonly associated behavioral and emotional problems. Ultimately, we propose that epigenetic processes provide an intriguing (although hypothetical) biological "platform" upon which ED relevant effects of perinatal insults, life stresses, and consequences of malnutrition may be registered, and argue that an epigenetically informed understanding may explain why EDs are triggered and maintained by excessive caloric restraint, why they coincide so frequently with mood- and impulse regulation problems, and why they tend to become increasingly entrenched over time. Finally, we comment on the clinical relevance and implications of an epigenetically informed model of ED etiology. PMID- 26836277 TI - Do low-calorie sweeteners promote weight gain in rodents? AB - Low-calorie sweeteners (LCSs) are used globally to increase the palatability of foods and beverages, without the calories of sugar. Recently, however, there have been claims that LCSs promote obesity. Here, I review the literature linking LCS consumption to elevated body weight in rodents. A recent systematic review found when the LCSs were presented in water or chow, only a minority of the studies reported elevated weight gain. In contrast, when the LCSs were presented in yogurt, the majority of the studies reported elevated weight gain. This review focuses on this latter subset of studies, and asks why the combination of LCSs and yogurt promoted weight gain. First, LCSs have been hypothesized to induce metabolic derangement because they uncouple sweet taste and calories. However, the available evidence indicates that the LCS-treated yogurts did not actually taste sweet to rats in the published studies. Without a sweet taste, the concerns about uncoupling sweet taste and calories would not be relevant. Second, in several studies, the LCS-treated yogurt increased weight gain without increasing caloric intake. This indicates that caloric intake alone cannot explain the elevated weight gain. Third, there is evidence that LCSs and yogurt can each alter the gut microbiota of rodents. Given recent work indicating that changes in gut microbiota can modulate body weight, it is possible that the combination of LCS and yogurt alters the gut microbiota in ways that promote weight gain. While this hypothesis remains speculative, it is consistent with the observed rodent data. In human studies, LCSs are usually presented in beverages. Based on the rodent work, it might be worthwhile to evaluate the impact of LCS-treated yogurt in humans. PMID- 26836276 TI - Baroreflex mechanisms in Irritable Bowel Syndrome: Part I. Traditional indices. AB - OBJECTIVE: This study was conducted to present evidence of differences in autonomic regulation of cardiovascular activity and its role in the severity of specific (disease-related) and non-specific (negative affect and chronic pain related) symptoms in individuals with Irritable Bowel Syndrome (IBS). METHODS: Seventy-eight female patients with IBS and 27 healthy women age 18-62 years were assessed for IBS symptoms, negative affect, and baroreceptor sensitivity (BRS), blood pressure (BP), heart rate, and heart rate variability (HRV) at rest. Direct and indirect regression effects were examined with application of the bootstrap procedure to validate findings. RESULTS: IBS was reliably related to lower resting BRS, higher BP, and higher negative affect compared to healthy controls. Longer disease duration (chronicity) was related to BRS decrease coupled with systolic BP increase (95% CIs=-0.14 to -0.01). Three autonomic mechanisms associated with BRS decrease were found to further regulate severity of IBS symptoms. Lower BRS was related to higher IBS severity in general if the effect was transferred through the decrease of low frequency power of HRV (e.g., 95% CIs=-0.039 to -0.001 for abdominal pain severity). However, lower BRS was related to lower IBS severity in general if the effect was transferred through diastolic BP increase (95% CIs=0.01-0.11 for abdominal pain severity). Lower BRS was related to higher abdominal pain severity coupled with high negative affect if the effect was transferred through the decrease of higher frequency power of HRV (95% CIs=-0.026 to -0.003). CONCLUSIONS: These findings indicate that different cardiovascular mechanisms are associated with IBS development and the increase and decrease of severity of IBS symptoms. Their assessment suggests ways to personalize treatment of IBS. PMID- 26836278 TI - Sex-specific attentional deficits in adult vitamin D deficient BALB/c mice. AB - Epidemiological studies have shown an association between vitamin D deficiency and cognitive impairment. However, there is a paucity of preclinical data showing that vitamin D deficiency is a causal factor for impaired cognitive processing. The aim of this study was to assess two cognitive tasks, the 5 choice-serial reaction task and the 5 choice-continuous performance task in adult vitamin D (AVD) deficient BALB/c mice. Ten-week old male and female BALB/c mice were fed a control or vitamin D deficient diet for 10 weeks prior to, and during behavioural testing. We found sex-dependent impairments in attentional processing and showed that male AVD-deficient mice were less accurate, took longer to respond when making a correct choice and were more likely to make an omission, without a change in the motivation to collect reward. By contrast, female AVD-deficient mice had a reduced latency to collect reward, but no changes on any other measures compared to controls. Therefore, we have shown that in otherwise healthy adult mice, vitamin D deficiency led to mild cognitive impairment in male but not female mice and therefore this model will be useful for future investigations into unravelling the mechanism by which vitamin D affects the adult brain and cognitive function. PMID- 26836279 TI - Nutraceuticals for body-weight management: The role of green tea catechins. AB - Green tea catechins mixed with caffeine have been proposed as adjuvants for maintaining or enhancing energy expenditure and for increasing fat oxidation, in the context of prevention and treatment of obesity. These catechins-caffeine mixtures seem to counteract the decrease in metabolic rate that occurs during weight loss. Their effects are of particular importance during weight maintenance after weight loss. Other metabolic targets may be fat absorption and the gut microbiota composition, but these effects still need further investigation in combination with weight loss. Limitations for the effects of green tea catechins are moderating factors such as genetic predisposition related to COMT-activity, habitual caffeine intake, and ingestion combined with dietary protein. In conclusion, a mixture of green tea catechins and caffeine has a beneficial effect on body-weight management, especially by sustained energy expenditure, fat oxidation, and preservation of fat free body-mass, after energy restriction induced body-weight loss, when taking the limitations into account. PMID- 26836280 TI - Reply to "Keep the sick from harm in spontaneous bacterial peritonitis: Dose of beta blockers matters". PMID- 26836282 TI - Continuously Controlled Optical Band Gap in Oxide Semiconductor Thin Films. AB - The optical band gap of the prototypical semiconducting oxide SnO2 is shown to be continuously controlled through single axis lattice expansion of nanometric films induced by low-energy helium implantation. While traditional epitaxy-induced strain results in Poisson driven multidirectional lattice changes shown to only allow discrete increases in bandgap, we find that a downward shift in the band gap can be linearly dictated as a function of out-of-plane lattice expansion. Our experimental observations closely match density functional theory that demonstrates that uniaxial strain provides a fundamentally different effect on the band structure than traditional epitaxy-induced multiaxes strain effects. Charge density calculations further support these findings and provide evidence that uniaxial strain can be used to drive orbital hybridization inaccessible with traditional strain engineering techniques. PMID- 26836281 TI - Is single portal vein perfusion the best approach for machine preservation of liver grafts? PMID- 26836283 TI - TNMF versus TNM in staging of colorectal cancer. AB - AIM: TNM staging and histological grading of rectal cancer has undergone no or minimal changes during the past 20 years despite their major impact on planning, reporting and outcome of the disease. The addition of category 'F' to the 'TNM' staging of colorectal cancer, which becomes TNMF will accommodate the expanding list of risk factors that may affect the management and thus avoid squeezing them into the TNM categories. METHODS: Reporting of the following risk factors was traced in 730 (664 retrospective and 66 prospective) cases of colorectal cancer: age, Tumor location, preoperative CEA, intraoperative tumor perforation and blood transfusion, quality of TME, tumor grade, non nodal T.Ds, Lymphovascular invasion, lymph node ratio, circumferential tumor margins, apical lymph nodes, infiltrating or pushing and K-ras gene mutation. RESULTS: The reporting of most risk factors was inadequate; also there is marked improvement in reporting in the prospective cases in preoperative CEA, intra operative blood transfusion and tumor perforation, quality of TME, tumor grade and non-nodal T.Ds (P-value <0.0001). CONCLUSION: The addition of category 'F' to the TNM staging system to become TNMF may avoid ignoring already established risk factors due to our inability to accommodate them in the inhospitable TNM categories. PMID- 26836285 TI - Location of knee pain in medial knee osteoarthritis: patterns and associations with self-reported clinical symptoms. AB - OBJECTIVES: To (1) document pain location in medial tibiofemoral osteoarthritis (OA) using the patient-administered Photographic Knee Pain Map (PKPM); (2) compare pain severity, nature and likelihood of neuropathic-like symptoms, physical dysfunction and presence of symptoms at other sites across the most common pain patterns. DESIGN: Baseline data were analysed from 164 participants with medial tibiofemoral OA (TFJOA) participating in a randomised controlled trial (RCT). Participants completed the PKPM indicating all relevant pain zones of their most painful knee. Pain zones were collapsed into regions to determine patterns of pain. Symptoms were quantified using numeric rating scales (NRSs) of pain severity, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Intermittent and Constant Osteoarthritis Pain (ICOAP) and painDETECT questionnaires. Symptoms at other joints were categorised as present/absent. RESULTS: The medial joint line (n = 123, 75%), patellar tendon (n = 62, 38%) and posterior knee (n = 61, 37%) were the most frequently reported pain zones. The most frequent patterns were diffuse (41%), isolated medial (16%), anterior-medial (12%) and medial-posterior (11%) pain. WOMAC and ICOAP scores were higher in the diffuse compared to anterior-medial patterns. Mean PainDETECT scores were higher with both diffuse and medial-posterior pain relative to anterior-medial pain. CONCLUSION: Only 16% of the cohort indicated isolated medial knee pain, whilst a diffuse pain pattern was most common. People with diffuse knee pain reported more severe pain and physical dysfunction than those with anterior-medial pain. Prevalence of possible/likely neuropathic-like symptoms tended to be more frequent in diffuse and posterior-medial patterns compared to anterior-medial pain. PMID- 26836284 TI - Folding of Fibroblast Growth Factor 1 Is Critical for Its Nonclassical Release. AB - Fibroblast growth factor 1 (FGF1), a ubiquitously expressed pro-angiogenic protein that is involved in tissue repair, carcinogenesis, and maintenance of vasculature stability, is released from the cells via a stress-dependent nonclassical secretory pathway. FGF1 secretion is a result of transmembrane translocation of this protein. It correlates with the ability of FGF1 to permeabilize membranes composed of acidic phospholipids. Like several other nonclassically exported proteins, FGF1 exhibits beta-barrel folding. To assess the role of folding of FGF1 in its secretion, we applied targeted mutagenesis in combination with a complex of biophysical methods and molecular dynamics studies, followed by artificial membrane permeabilization and stress-induced release experiments. It has been demonstrated that a mutation of proline 135 located in the C-terminus of FGF1 results in (i) partial unfolding of FGF1, (ii) a decrease in FGF1's ability to permeabilize bilayers composed of phosphatidylserine, and (iii) drastic inhibition of stress-induced FGF1 export. Thus, folding of FGF1 is critical for its nonclassical secretion. PMID- 26836286 TI - Changes in knee joint load indices from before to 12 months after arthroscopic partial meniscectomy: a prospective cohort study. AB - OBJECTIVE: Patients undergoing arthroscopic partial meniscectomy (APM) are at increased risk of knee osteoarthritis (OA). Meniscal damage and/or surgery may alter knee joint loading to increase OA risk. We investigated changes in knee joint loading following medial APM surgery, compared with the contra-lateral leg. METHODS: We estimated indices of knee joint loading (external peak knee adduction moment (KAM), KAM impulse and peak knee flexion moment (KFM)) normalized to body size (i.e., body mass (BM) and height (HT)) using 3D gait analysis in 23 patients (17 men, mean (SD) 46.2 (6.4) years, BMI 25.8 (3.4) kg/m(2)) without radiographic knee OA before and 12 months after medial APM. Static alignment was assessed by radiography and self-reported outcomes by Knee injury and Osteoarthritis Outcome Score (KOOS). RESULTS: Peak KAM and KAM impulse increased in the APM leg compared to the contra-lateral leg from before to 12 months after surgery (change difference: 0.38 Nm/BM*HT% 95% CI 0.01 to 0.76 (P = 0.049) and 0.20 Nm*s/BM*HT% 95% CI 0.10 to 0.30 (P < 0.001)). Patients self-reported improvements on all KOOS subscales (KOOS pain improvement: 22.8 95% CI 14.5 to 31.0 (P < 0.01)). CONCLUSIONS: A relative increase in indices of medial compartment loading was observed in the leg undergoing APM compared with the contra-lateral leg from before to 12 months after surgery. This increase may contribute to the elevated risk of knee OA in these patients. Randomized trials including a non-surgical control group are needed to determine if changes in joint loading following APM are caused by surgery or by changes in symptoms. PMID- 26836287 TI - Changes in patellofemoral and tibiofemoral joint cartilage damage and bone marrow lesions over 7 years: the Multicenter Osteoarthritis Study. AB - OBJECTIVES: To investigate changes in cartilage damage and bone marrow lesions (BMLs) on MRI in the patellofemoral and tibiofemoral joints (TFJs) over 7 years. METHODS: The Multicenter Osteoarthritis (MOST) Study is a cohort study of persons aged 50-79 years at baseline with or at high risk for knee osteoarthritis (OA). Knees were eligible for the current study if they had knee MRI (1.0T) assessed for cartilage damage and BMLs at the baseline and 84-month visits. Knees were categorized as having MRI-detected structural damage (cartilage and BMLs) isolated to the patellofemoral joint (PFJ), isolated to the TFJ, mixed or no damage at baseline and 84-months. We determined the changes in PFJ and TFJ structural damage over 7 years and used logistic regression to assess the relation of baseline compartment distribution to incident isolated PFJ, isolated TFJ and mixed damage. RESULTS: Among 339 knees that had full-thickness cartilage loss isolated to the PFJ or TFJ at baseline, only 68 (20.1%) developed full thickness cartilage loss in the other compartment while 271 (79.9%) continued to only have the initial compartment affected. Compared to knees without full thickness cartilage damage (n = 582), those with isolated TFJ and PFJ full thickness cartilage damage had 2.7 (1.5, 4.9) and 5.8 (3.6, 9.6) times the odds of incident mixed full-thickness cartilage damage, respectively. Similar results were seen when using other definitions of MRI-defined structural damage. CONCLUSIONS: Most knees with structural damage at baseline do not develop it in the other compartment. Knees that develop mixed structural damage are more likely to start with it isolated to the PFJ. PMID- 26836289 TI - Propagation of SH waves in an infinite/semi-infinite piezoelectric/piezomagnetic periodically layered structure. AB - In this paper, SH bulk/surface waves propagating in the corresponding infinite/semi-infinite piezoelectric (PE)/piezomagnetic (PM) and PM/PE periodically layered composites are investigated by two methods, the stiffness matrix method and the transfer matrix method. For a semi-infinite PE/PM or PM/PE medium, the free surface is parallel to the layer interface. Both PE and PM materials are assumed to be transversely isotropic solids. Dispersion equations are derived by the stiffness/transfer matrix methods, respectively. The effects of electric-magnetic (ME) boundary conditions at the free surface and the layer thickness ratios on dispersion curves are considered in detail. Numerical examples show that the results calculated by the two methods are the same. The dispersion curves of SH surface waves are below the bulk bands or inside the frequency gaps. The ratio of the layer thickness has an important effect not only on the bulk bands but also on the dispersion curves of SH surface waves. Electric and magnetic boundary conditions, respectively, determine the dispersion curves of SH surface waves for the PE/PM and PM/PE semi-infinite structures. The band structures of SH bulk waves are consistent for the PE/PM and PM/PE structures, however, the dispersive behaviors of SH surface waves are indeed different for the two composites. The realization of the above-mentioned characteristics of SH waves will make it possible to design PE/PM acoustic wave devices with periodical structures and achieve the better performance. PMID- 26836288 TI - The OA Trial Bank: meta-analysis of individual patient data from knee and hip osteoarthritis trials show that patients with severe pain exhibit greater benefit from intra-articular glucocorticoids. AB - OBJECTIVE: To evaluate the efficacy of intra-articular (IA) glucocorticoids for knee or hip osteoarthritis (OA) in specific subgroups of patients with severe pain and inflammatory signs using individual patient data (IPD) from existing trials. DESIGN: Randomized trials evaluating one or more IA glucocorticoid preparation in patients with knee or hip OA, published from 1995 up to June 2012 were selected from the literature. IPD obtained from original trials included patient and disease characteristics and outcomes measured. The primary outcome was pain severity at short-term follow-up (up to 4 weeks). The subgroup factors assessed included severe pain (>=70 points, 0-100 scale) and signs of inflammation (dichotomized in present or not) at baseline. Multilevel regression analyses were applied to estimate the magnitude of the effects in the subgroups with the individuals nested within each study. RESULTS: Seven out of 43 published randomized clinical trials (n = 620) were included. Patients with severe baseline pain had a significantly larger reduction in short-term pain, but not in mid- and long-term pain, compared to those with less severe pain at baseline (Mean Difference 13.91; 95% Confidence Interval 1.50-26.31) when receiving IA glucocorticoid injection compared to placebo. No statistical significant interaction effects were found between inflammatory signs and IA glucocorticoid injections compared to placebo and to tidal irrigation at all follow-up points. CONCLUSIONS: This IPD meta-analysis demonstrates that patients with severe knee pain at baseline derive more benefit from IA glucocorticoid injection at short term follow-up than those with less severe pain at baseline. PMID- 26836290 TI - Extended optical theorem for scalar monochromatic acoustical beams of arbitrary wavefront in cylindrical coordinates. AB - One of the fundamental theorems in (optical, acoustical, quantum, gravitational) wave scattering is the optical theorem for plane waves, which relates the extinction cross-section to the forward scattering complex amplitude function. In this analysis, the optical theorem is extended for the case of 3D-beams of arbitrary character in a cylindrical coordinates system for any angle of incidence and any scattering angle. Generalized analytical expressions for the extinction, absorption, scattering cross-sections and efficiency factors are derived in the framework of the scalar resonance scattering theory for an object of arbitrary shape. The analysis reveals the presence of an interference scattering cross-section term, which describes interference between the diffracted or specularly reflected inelastic (Franz) waves with the resonance elastic waves. Moreover, an alternate expression for the extinction cross section, which relates the resonance cross-section with the scattering cross section for an impenetrable object, is obtained, suggesting an improved method for particle characterization. Cross-section expressions are also derived for known acoustical wavefronts centered on the object, defined as the on-axis case. The extended optical theorem in cylindrical coordinates can be applied to evaluate the extinction efficiency from any object of arbitrary geometry placed on or off the axis of the incident beam. Applications in acoustics, optics, and quantum mechanics should benefit from this analysis in the context of wave scattering theory and other phenomena closely connected to it, such as the multiple scattering by many particles, as well as the radiation force and torque. PMID- 26836291 TI - A computer simulation study of soft tissue characterization using low-frequency ultrasonic tomography. AB - We investigate the potential of using ultrasonic diffraction tomography technique for characterization of biological tissues. Unlike most of other studies where ultrasonic tomography operates at frequencies higher than 1 MHz, low-frequency tomography uses lower frequencies on the order of 0.3-0.5 MHz. Such a choice is due to low attenuation at these frequencies, resulting in higher precision of input data. In this paper we explore transmission and reflection schemes for both 2D (layer-by-layer) and 3D tomography. We treat inverse tomography problems as coefficient inverse problems for the wave equation. The time-domain algorithms employed for solving the inverse problem of low-frequency tomography focus on the use of GPU clusters. The results obtained show that a spatial resolution of about 2-3mm can be achieved when operating at the wavelength of about 5mm even using a stationary 3D scheme with a few fixed sources and no rotating elements. The study primarily focuses on determining the performance limits of ultrasonic tomography devices currently designed for breast cancer diagnosis. PMID- 26836292 TI - Pregabalin for decreasing pancreatic pain in chronic pancreatitis. AB - BACKGROUND: Chronic abdominal pain is one of the major symptoms in people with chronic pancreatitis. The role of pregabalin in people with chronic pancreatic pain due to chronic pancreatitis is uncertain. OBJECTIVES: To assess the benefits and harms of pregabalin in people with chronic abdominal pain due to chronic pancreatitis. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2015, issue 6, and MEDLINE, EMBASE, Science Citation Index Expanded, trials registers until June 2015. We also searched the references of included trials to identify further trials. SELECTION CRITERIA: We considered only randomised controlled trials (RCT) performed in people with chronic pancreatic pain due to chronic pancreatitis, irrespective of language, blinding, or publication status for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and independently extracted data. We calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) with RevMan 5, based on intention-to-treat analysis. MAIN RESULTS: Only one study, funded by Pfizer, met the inclusion criteria for the review. A total of 64 participants (with chronic pain due to chronic pancreatitis) were randomly assigned to receive escalating doses of pregabalin (150 mg per day to 600 mg per day; 34 participants) or matching placebo (30 participants). Participants received pregabalin or placebo for three weeks on an outpatient basis; the outcomes were measured at the end of the treatment (i.e. three weeks from commencement of treatment). Potential participants taking concomitant analgesic medication and expected to stay on a stable regime during the trial were allowed to enter the study. This trial was at low risk of bias. The overall quality of evidence was low or moderate.Only the short-term outcomes were available in this trial. The medium and long-term outcomes, number of work days lost, and length of hospital stay due to admissions for pain control were not available. This trial found that the changes in opiate use (MD -26.00 mg; 95% CI -47.36 to -4.64; participants = 64; moderate-quality evidence), and pain score percentage changes from baseline (MD -12.00; 95% CI 21.82 to -2.18; participants = 64; moderate-quality evidence) were better in participants taking pregabalin compared to those taking placebo. This trial also found that there were more adverse events in participants taking pregabalin compared to those taking placebo (RR 1.71; 95% CI 1.20 to 2.43; participants = 64). The differences between pregabalin and placebo were imprecise for short-term health-related quality of life measured with the EORTC CLQ-30 questionnaire (MD 11.40; 95% CI -3.28 to 26.08; participants = 64; moderate-quality evidence), proportion of people with serious adverse events (RR 1.76; 95% CI 0.35 to 8.96; participants = 64; low-quality evidence), and proportion of people requiring hospital admissions (RR 0.44; 95% CI 0.04 to 4.62; participants = 64; low quality evidence). AUTHORS' CONCLUSIONS: Based on low- to moderate-quality evidence, short-term use of pregabalin decreases short-term opiate use, and short-term pain scores, but increases the adverse events compared to placebo, in people with chronic pain due to chronic pancreatitis. The clinical implication of the decreases in short-term opiate use and short-term pain scores is not known.Future trials assessing the role of pregabalin in decreasing chronic pain in chronic pancreatitis should assess the medium- or long-term effects of pregabalin and should include outcomes such as, quality of life, treatment-related adverse events, number of work days lost, number of hospital admissions, and the length of hospital stay, in addition to pain scores, to assess the clinical and socioeconomic impact. PMID- 26836293 TI - Controlled mineralisation and recrystallisation of brushite within alginate hydrogels. AB - Due to high solubility and fast resorption behaviour under physiological conditions, brushite (CaHPO4?2H2O, calcium monohydrogen phosphate dihydrate, dicalcium phosphate dihydrate) has great potential in bone regeneration applications, both in combination with scaffolds or as a component of calcium phosphate cements. The use of brushite in combination with hydrogels opens up possibilities for new cell-based tissue engineering applications of this promising material. However, published preparation methods of brushite composites, in which the mineral phase is precipitated within the hydrogel network, fail to offer the necessary degree of control over the mineral phase, content and distribution within the hydrogel matrix. The main focus of this study is to address these shortcomings by determining the precise fabrication parameters needed to prepare composites with controlled composition and properties. Composite alginate microbeads were prepared using a counter-diffusion technique, which allows for the simultaneous crosslinking of the hydrogel and precipitation of an inorganic mineral phase. Reliable nucleation of a desired mineral phase within the alginate network proved more challenging than simple aqueous precipitation. This was largely due to ion transport within the hydrogel producing concentration gradients that modified levels of supersaturation and favoured the nucleation of other phases such as hydroxyapatite and octacalcium phosphate, which would otherwise not form. To overcome this, the incorporation of brushite seed crystals resulted in good control during the mineral phase, and by adjusting the number of seeds and amount of precursor concentration, the amount of mineral could be tuned. The material was characterised with a range of physical techniques, including scanning electron microscopy, powder x-ray diffraction and Rietveld refinement, Fourier transform infrared spectroscopy, and thermogravimetric analysis, in order to assess the mineral morphology, phase and amount within the organic matrix. The mineral content of the composite material converted from brushite into hydroxyapatite when submerged in simulated body fluid, indicating possible bioactivity. Additionally, initial cell culture studies revealed that both the material and the synthesis procedure are compatible with cells relevant to bone tissue engineering. PMID- 26836294 TI - Arterial Anastomosis in the Tongue. AB - PURPOSE: Radical surgery for neoplasms of the tongue can endanger at least 1 lingual artery, threatening the survival of the remaining tissue and the recovery of speech and swallowing. Although there is little anastomosis in the substance of the tongue, this study investigated whether arterial anastomoses outside the tongue could provide collateral circulation to protect the surviving tissue. MATERIALS AND METHODS: Parts of 9 embalmed cadaver heads were examined. In 2 specimens, the arteries had been previously injected with latex and India ink. In the remaining, a mixture of latex and India ink was injected into the lingual artery at its origin on 1 side. Five injections were successful. RESULTS: There was considerable variation in the course and distribution of the lingual arteries. Arteries did not cross the midline of the tongue, but actual or potential anastomoses could be seen round the base of the tongue, in the floor of the mouth, and with facial artery branches. After the experimental injections, the mass filled the lingual artery and its branches on the injected side, but also reached the trunk and main branches of the opposite side. CONCLUSION: A mass injected into the lingual artery of 1 side can reach the trunk and territory of the lingual artery of the opposite side. In life, it is likely that a similar collateral circulation would exist. Some clinical literature supports this conclusion, but preoperative arteriography might be a reasonable precaution. PMID- 26836295 TI - DNA methylation profiling of primary neuroblastoma tumors using methyl-CpG binding domain sequencing. AB - Comprehensive genome-wide DNA methylation studies in neuroblastoma (NB), a childhood tumor that originates from precursor cells of the sympathetic nervous system, are scarce. Recently, we profiled the DNA methylome of 102 well-annotated primary NB tumors by methyl-CpG-binding domain (MBD) sequencing, in order to identify prognostic biomarker candidates. In this data descriptor, we give details on how this data set was generated and which bioinformatics analyses were applied during data processing. Through a series of technical validations, we illustrate that the data are of high quality and that the sequenced fragments represent methylated genomic regions. Furthermore, genes previously described to be methylated in NB are confirmed. As such, these MBD sequencing data are a valuable resource to further study the association of NB risk factors with the NB methylome, and offer the opportunity to integrate methylome data with other -omic data sets on the same tumor samples such as gene copy number and gene expression, also publically available. PMID- 26836296 TI - Shame, Catastrophizing, and Negative Partner Responses Are Associated With Lower Sexual and Relationship Satisfaction and More Negative Affect in Men With Peyronie's Disease. AB - Peyronie's disease (PD) has a negative impact on men's sexual functioning and quality of life, but little is known about why some men cope better than others and what the effects of PD are on their relationships. The aims of the present study were to describe negative affect, pain, and relationship and sexual satisfaction in men with PD, and to explore their psychosocial correlates. Participants were 110 men diagnosed with PD. All men completed questionnaires. The main outcome measures were as follows: Global Measure of Sexual Satisfaction, Dyadic Adjustment Scale, McGill Pain Questionnaire, and Negative Affect Scale. The predictor variables were the following: Experience of Shame Scale, Body Esteem Scale, Body Image Self-Consciousness Scale, Index of Male Genital Image, a modified Pain Catastrophizing Scale, and a modified Multidimensional Pain Inventory. Although men with PD had mean sexual/relationship satisfaction and negative affect scores indicating mild impairment, there was a wide range of variation, with 42% to 52% scoring in the clinical range. Catastrophizing was significantly associated with reduced sexual satisfaction and increased negative affect and pain. Shame was also associated with increased negative affect. The significant associations of relationship satisfaction were partner responses and shame. Given the lack of curative treatment in PD, understanding why some men cope better than others may guide therapy. Shame, catastrophizing, and partner responses may be important therapeutic targets. PMID- 26836297 TI - Mathematical model to interpret localized reflectance spectra measured in the presence of a strong fluorescence marker. AB - Quantification of multiple fluorescence markers during neurosurgery has the potential to provide complementary contrast mechanisms between normal and malignant tissues, and one potential combination involves fluorescein sodium (FS) and aminolevulinic acid-induced protoporphyrin IX (PpIX). We focus on the interpretation of reflectance spectra containing contributions from elastically scattered (reflected) photons as well as fluorescence emissions from a strong fluorophore (i.e., FS). A model-based approach to extract MUa and MU's in the presence of FS emission is validated in optical phantoms constructed with Intralipid (1% to 2% lipid) and whole blood (1% to 3% volume fraction), over a wide range of FS concentrations (0 to 1000 MUg/ml 1000 MUg/ml ). The results show that modeling reflectance as a combination of elastically scattered light and attenuation-corrected FS-based emission yielded more accurate tissue parameter estimates when compared with a nonmodified reflectance model, with reduced maximum errors for blood volume (22% versus 90%), microvascular saturation (21% versus 100%), and MUs' (13% versus 207%). Additionally, quantitative PpIX fluorescence sampled in the same phantom as FS showed significant differences depending on the reflectance model used to estimate optical properties (i.e., maximum error 29% versus 86%). These data represent a first step toward using quantitative optical spectroscopy to guide surgeries through simultaneous assessment of FS and PpIX. PMID- 26836298 TI - High energy supercontinuum sources using tapered photonic crystal fibers for multispectral photoacoustic microscopy. AB - We demonstrate a record bandwidth high energy supercontinuum source suitable for multispectral photoacoustic microscopy. The source has more than 150 nJ/10 nm bandwidth over a spectral range of 500 to 1600 nm. This performance is achieved using a carefully designed fiber taper with large-core input for improved power handling and small-core output that provides the desired spectral range of the supercontinuum source. PMID- 26836299 TI - Socially constructed 'value' and vocational experiences following neurological injury. AB - PURPOSE: Paid work is seen as a key outcome in rehabilitation. However, research demonstrates that because of normative expectations in the job market and workplace, experiences of disability can be intensified in a work context. We sought to explore this issue in more depth by analysing the effects of societal constructions of worker 'value' within individual case studies of people with acquired neurological injury. METHOD: Instrumental case study of four heterogeneous participants, employing a discourse analysis approach. RESULTS: Participants described a perpetuation of discourses in which a disabled body or mind itself is seen to qualify, disqualify or limit a person's value in employment. Nevertheless, interviews also highlighted discourses that constructed other worker identities: based on pre-injury identities, life experiences and other aspects of self. The contrasts between individuals illustrated how worker identities, when situated within broader societal discourses of worker 'value', can either constrain or expand the vocational opportunities available to individuals who experience disability. However, current and historical interactions about worker 'value' shaped the identities genuinely available to each individual. CONCLUSION: Understanding how societal discourses enable and constrain worker identities may be vital to (a) facilitating valid opportunities and (b) navigating situations that could unintentionally hinder vocational possibilities. Implications for Rehabilitation This study shows how worker identities, situated within societal discourses of worker 'value', can constrain or broaden vocational opportunities available to individuals who experience disability. Barriers to gaining, maintaining and developing in employment could be re-envisaged in terms of what is limiting a person's ability to embody an enabling identity. A knowledge of both societal discourses and individuals' interactions with them may be vital to facilitating opportunities that users of rehabilitation services experience as valid options. This knowledge can also provide information with which to navigate situations that could potentially (sometimes unintentionally) constrain vocational possibilities. PMID- 26836300 TI - Molecular and Cytogenetic Characterization of a Powdery Mildew-Resistant Wheat Aegilops mutica Partial Amphiploid and Addition Line. AB - Aegilops mutica Boiss., a diploid species (2n = 2x = 14, TT), has been rarely studied before. In this research, a hexaploid wheat (cv. Chinese Spring)-Ae. mutica partial amphiploid and a wheat-Ae. mutica addition line were characterized by chromosome karyotyping, FISH using oligonucleotides Oligo-pTa535-1, Oligo pSc119.2-1, and (GAA)8 as probes, and EST-based molecular markers. The results showed that the partial amphiploid strain consisted of 20 pairs of wheat chromosomes and 7 pairs of Ae. mutica chromosomes, with both wheat 7B chromosomes missing. EST-based molecular marker data suggested that the wheat-Ae. mutica addition line carries the 7T chromosome. Resistance tests indicated that both the partial amphiploid and the 7T addition line were highly resistant to powdery mildew, whereas the wheat control line Chinese Spring was highly susceptible, indicating the presence of a potentially new powdery mildew resistance gene on the Ae. mutica 7T chromosome. The karyotype, FISH patterns, and molecular markers can now be used to identify Ae. mutica chromatin in a wheat background, and the 7T addition could be used as a new powdery mildew resistance source for wheat breeding. PMID- 26836301 TI - "Harder, Better, Faster, Stronger": Negative Comparison on Facebook and Adolescents' Life Satisfaction Are Reciprocally Related. AB - Social networking sites, such as Facebook, offer adolescent users an ideal platform for negative comparison (i.e., experiencing negative feelings from social comparison). Although such negative comparison on Facebook has been associated with users' well-being, the reciprocal relations between the two remain unclear, particularly in an adolescent sample. To examine this reciprocal process, a two-wave study among a representative sample of Flemish adolescents was set up (N Time1 = 1,840). Data were analyzed using structural equation modeling. Cross-lagged analyses indicated that negative comparison on Facebook predicted decreases in life satisfaction over time. Conversely, lower scores on life satisfaction predicted increases in negative comparison on Facebook. The discussion focuses on the understanding of these findings, key limitations, directions for future research, and implications for prevention and intervention strategies. PMID- 26836302 TI - Clinicopathological features in anterior visual pathway in neuromyelitis optica. AB - OBJECTIVE: Neuromyelitis optica spectrum disorder (NMOsd) is an autoimmune disorder of the central nervous system characterized by aquaporin-4 (AQP4) autoantibodies. The aim of this study was to elucidate the characteristics of involvement of the anterior visual pathway (AVP) and neurodegeneration via glia neuron interaction in NMOsd. METHODS: Thirty Japanese patients with serologically verified NMOsd were assessed with a neuro-ophthalmological study. Using 27 tissue blocks from 13 other cases of NMOsd, we performed neuropathological analysis of glial and neuroaxonal involvement in the AVP. RESULTS: The AVP involvement in NMOsd was characterized by the following, compared to multiple sclerosis: (1) longitudinally extensive optic neuritis (ON); (2) more severe visual impairment and worse prognosis for ON; (3) unique AQP4 dynamics, including loss of AQP4 immunoreactivity on astrocytes with complement activation in ON lesions, loss of AQP4 immunoreactivity on Muller cells with no deposition of complement in the retinas, and densely packed AQP4 immunoreactivity on astrocytes in gliosis of secondary anterograde/retrograde degeneration in the optic nerves and retinal nerve fiber layer (RNFL); and (4) more severe neurodegeneration, including axonal accumulation of degenerative mitochondria and transient receptor potential melastatin 4 channel with complement-dependent astrocyte pathology in ON lesions, mild loss of horizontal cells, and RNFL thinning and loss of ganglion cells with abundance of AQP4(+) astrocytes, indicating secondary retrograde degeneration after ON. INTERPRETATION: Severe and widespread neuroaxonal damage and unique dynamics of astrocytes/Muller cells with alterations of AQP4 were prominent in the AVP and may be associated with poor visual function and prognosis in NMOsd. PMID- 26836303 TI - A feedback mechanism converts individual cell features into a supracellular ECM structure in Drosophila trachea. AB - The extracellular matrix (ECM), a structure contributed to and commonly shared by many cells in an organism, plays an active role during morphogenesis. Here, we used the Drosophila tracheal system to study the complex relationship between the ECM and epithelial cells during development. We show that there is an active feedback mechanism between the apical ECM (aECM) and the apical F-actin in tracheal cells. Furthermore, we reveal that cell-cell junctions are key players in this aECM patterning and organisation and that individual cells contribute autonomously to their aECM. Strikingly, changes in the aECM influence the levels of phosphorylated Src42A (pSrc) at cell junctions. Therefore, we propose that Src42A phosphorylation levels provide a link for the ECM environment to ensure proper cytoskeletal organisation. PMID- 26836304 TI - Mapping oxygen concentration in the awake mouse brain. AB - Although critical for brain function, the physiological values of cerebral oxygen concentration have remained elusive because high-resolution measurements have only been performed during anesthesia, which affects two major parameters modulating tissue oxygenation: neuronal activity and blood flow. Using measurements of capillary erythrocyte-associated transients, fluctuations of oxygen partial pressure (Po2) associated with individual erythrocytes, to infer Po2 in the nearby neuropil, we report the first non-invasive micron-scale mapping of cerebral Po2 in awake, resting mice. Interstitial Po2 has similar values in the olfactory bulb glomerular layer and the somatosensory cortex, whereas there are large capillary hematocrit and erythrocyte flux differences. Awake tissue Po2 is about half that under isoflurane anesthesia, and within the cortex, vascular and interstitial Po2 values display layer-specific differences which dramatically contrast with those recorded under anesthesia. Our findings emphasize the importance of measuring energy parameters non-invasively in physiological conditions to precisely quantify and model brain metabolism. PMID- 26836305 TI - Nucleophosmin integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA. AB - The nucleolus is a membrane-less organelle formed through liquid-liquid phase separation of its components from the surrounding nucleoplasm. Here, we show that nucleophosmin (NPM1) integrates within the nucleolus via a multi-modal mechanism involving multivalent interactions with proteins containing arginine-rich linear motifs (R-motifs) and ribosomal RNA (rRNA). Importantly, these R-motifs are found in canonical nucleolar localization signals. Based on a novel combination of biophysical approaches, we propose a model for the molecular organization within liquid-like droplets formed by the N-terminal domain of NPM1 and R-motif peptides, thus providing insights into the structural organization of the nucleolus. We identify multivalency of acidic tracts and folded nucleic acid binding domains, mediated by N-terminal domain oligomerization, as structural features required for phase separation of NPM1 with other nucleolar components in vitro and for localization within mammalian nucleoli. We propose that one mechanism of nucleolar localization involves phase separation of proteins within the nucleolus. PMID- 26836306 TI - Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation. AB - Upon fertilization, the highly specialised sperm and oocyte genomes are remodelled to confer totipotency. The mechanisms of the dramatic reprogramming events that occur have remained unknown, and presumed roles of histone modifying enzymes are just starting to be elucidated. Here, we explore the function of the oocyte-inherited pool of a histone H3K4 and K9 demethylase, LSD1/KDM1A during early mouse development. KDM1A deficiency results in developmental arrest by the two-cell stage, accompanied by dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns. At the transcriptional level, the switch of the maternal-to zygotic transition fails to be induced properly and LINE-1 retrotransposons are not properly silenced. We propose that KDM1A plays critical roles in establishing the correct epigenetic landscape of the zygote upon fertilization, in preserving genome integrity and in initiating new patterns of genome expression that drive early mouse development. PMID- 26836307 TI - Waves of actin and microtubule polymerization drive microtubule-based transport and neurite growth before single axon formation. AB - Many developing neurons transition through a multi-polar state with many competing neurites before assuming a unipolar state with one axon and multiple dendrites. Hallmarks of the multi-polar state are large fluctuations in microtubule-based transport into and outgrowth of different neurites, although what drives these fluctuations remains elusive. We show that actin waves, which stochastically migrate from the cell body towards neurite tips, direct microtubule-based transport during the multi-polar state. Our data argue for a mechanical control system whereby actin waves transiently widen the neurite shaft to allow increased microtubule polymerization to direct Kinesin-based transport and create bursts of neurite extension. Actin waves also require microtubule polymerization, arguing that positive feedback links these two components. We propose that actin waves create large stochastic fluctuations in microtubule based transport and neurite outgrowth, promoting competition between neurites as they explore the environment until sufficient external cues can direct one to become the axon. PMID- 26836310 TI - Five-Year Bibliometric Review of Genomic Nursing Science Research. AB - PURPOSE: This bibliometric review profiles the focus, dissemination, and impact of genomic nursing science articles from 2010 to 2014. DESIGN: Data-based genomic nursing articles by nursing authors and articles by non-nurse principal investigators funded by the National Institute of Nursing Research were categorized into the Genomic Nursing Science Blueprint nursing areas. METHODS: Bibliometric content analysis was used. FINDINGS: A total of 197 articles met the inclusion criteria. Of these, 60.3% were on biologic plausibility, 12.1% on client self-management, 11.1% on decision making or decision support, 8.1% on family, and 4.0% on communication, with the remaining 4.0% of articles focused on other topics. Few (11.6%) addressed healthcare disparities in the study purpose. Thirty-four references (17.2%) were cited 10 or more times. CONCLUSIONS: Research based genomic nursing science articles are in the discovery phase of inquiry. All topics were investigated in more than one country. Healthcare disparities were addressed in few studies. Research findings from interdisciplinary teams were disseminated beyond nursing audiences, with findings addressing biologic discovery, decision making or support, and family being cited most frequently. Gaps in the reviewed articles included cross-cutting themes, ethics, and clinical utility. Interdisciplinary research is needed to document clinical and system outcomes of genomic nursing science implementation in health care. CLINICAL RELEVANCE: Although the review identifies areas that are encountered in clinical practice, relevance to practice will depend on evaluation of findings and subsequent development of clinical guidelines. PMID- 26836309 TI - Fast turnover of genome transcription across evolutionary time exposes entire non coding DNA to de novo gene emergence. AB - Deep sequencing analyses have shown that a large fraction of genomes is transcribed, but the significance of this transcription is much debated. Here, we characterize the phylogenetic turnover of poly-adenylated transcripts in a comprehensive sampling of taxa of the mouse (genus Mus), spanning a phylogenetic distance of 10 Myr. Using deep RNA sequencing we find that at a given sequencing depth transcriptome coverage becomes saturated within a taxon, but keeps extending when compared between taxa, even at this very shallow phylogenetic level. Our data show a high turnover of transcriptional states between taxa and that no major transcript-free islands exist across evolutionary time. This suggests that the entire genome can be transcribed into poly-adenylated RNA when viewed at an evolutionary time scale. We conclude that any part of the non-coding genome can potentially become subject to evolutionary functionalization via de novo gene evolution within relatively short evolutionary time spans. PMID- 26836311 TI - Leaping without Looking--Duty Hours, Autonomy, and the Risks of Research and Practice. PMID- 26836308 TI - Estrogen receptor alpha somatic mutations Y537S and D538G confer breast cancer endocrine resistance by stabilizing the activating function-2 binding conformation. AB - Somatic mutations in the estrogen receptor alpha (ERalpha) gene (ESR1), especially Y537S and D538G, have been linked to acquired resistance to endocrine therapies. Cell-based studies demonstrated that these mutants confer ERalpha constitutive activity and antiestrogen resistance and suggest that ligand-binding domain dysfunction leads to endocrine therapy resistance. Here, we integrate biophysical and structural biology data to reveal how these mutations lead to a constitutively active and antiestrogen-resistant ERalpha. We show that these mutant ERs recruit coactivator in the absence of hormone while their affinities for estrogen agonist (estradiol) and antagonist (4-hydroxytamoxifen) are reduced. Further, they confer antiestrogen resistance by altering the conformational dynamics of the loop connecting Helix 11 and Helix 12 in the ligand-binding domain of ERalpha, which leads to a stabilized agonist state and an altered antagonist state that resists inhibition. PMID- 26836312 TI - Guest-Induced Breathing Effect in a Flexible Molecular Crystal. AB - By introducing a flexible component into a molecular building block, we present an unprecedented alkyl-decorated flexible crystalline material with a breathing behavior. Its selective adsorption is derived from the breathing effect induced by a guest triggered alkyl transformation. This feature allows the crystal to take up 2.5 mmol g(-1) of chloroform with high adsorption selectivity (CHCl3 /EA >2000 for example), implying a potential application in sorption separation and chemical sensors. PMID- 26836313 TI - New-Generation Graphene from Electrochemical Approaches: Production and Applications. AB - Extensive research suggests a bright future for the graphene market. However, for a long time there has been a huge gap between laboratory-scale research and commercial application due to the challenging task of reproducible bulk production of high-quality graphene at low cost. Electrochemical exfoliation of graphite has emerged as a promising wet chemical method with advantages such as upscalability, solution processability and eco-friendliness. Recent progress in the electrochemical exfoliation of graphite and prospects for the application of exfoliated graphene, mainly in the fields of composites, electronics, energy storage and conversion are discussed. PMID- 26836315 TI - AAE13 encodes a dual-localized malonyl-CoA synthetase that is crucial for mitochondrial fatty acid biosynthesis. AB - Malonyl-CoA is a key intermediate in a number of metabolic processes associated with its role as a substrate in acylation and condensation reactions. These types of reactions occur in plastids, the cytosol and mitochondria, and although carboxylation of acetyl-CoA is the known mechanism for generating the distinct plastidial and cytosolic pools, the metabolic origin of the mitochondrial malonyl CoA pool is still unclear. In this study we demonstrate that malonyl-CoA synthetase encoded by the Arabidopsis AAE13 (AT3G16170) gene is localized in both the cytosol and the mitochondria. These isoforms are translated from two types of transcripts, one that contains and one that does not contain a mitochondrial targeting pre-sequence. Whereas the cytosolic AAE13 protein is not essential, due to the presence of a redundant malonyl-CoA generating system provided by a cytosolic acetyl-CoA carboxylase, the mitochondrial AAE13 protein is essential for plant growth. Phenotypes of the aae13-1 mutant are transgenically reversed only if the mitochondrial pre-sequence is present in the ectopically expressed AAE13 proteins. The aae13-1 mutant exhibits typical metabolic phenotypes associated with a deficiency in the mitochondrial fatty acid synthase system, namely depleted lipoylation of the H subunit of the photorespiratory enzyme glycine decarboxylase, increased accumulation of glycine and glycolate and reduced levels of sucrose. Most of these metabolic alterations, and associated morphological changes, are reversed when the aae13-1 mutant is grown in a non photorespiratory condition (i.e. a 1% CO2 atmosphere), demonstrating that they are a consequence of the deficiency in photorespiration due to the inability to generate lipoic acid from mitochondrially synthesized fatty acids. PMID- 26836316 TI - Enantiomeric Excess Sensitivity to Below One Percent by Using Femtosecond Photoelectron Circular Dichroism. AB - Photoelectron circular dichroism (PECD) is experimentally investigated with chiral specimens with varying amounts of enantiomeric excess (ee). As a prototype, we measure and analyze the photoelectron angular distribution from randomly oriented fenchone molecules in the gas phase that result from ionization with circularly polarized femtosecond laser pulses. The quantification of these measurements shows a linear dependence with respect to the ee values. In addition, differences in the ee values (denoted as detection limit) of below one percent can be distinguished for nearly enantiopure samples, as well as for almost racemates. In combination with the use of a reference, the assignment of absolute ee values is possible. The present measurement time is a few minutes, but this could be reduced. This table-top laser-based approach should facilitate widespread implementation in chiral analysis. PMID- 26836317 TI - Determinants of serum 25-hydroxyvitamin D concentration in Finnish children: the Physical Activity and Nutrition in Children (PANIC) study. AB - We studied vitamin D intake, serum 25-hydroxyvitamin D (S-25(OH)D) concentration, determinants of S-25(OH)D and risk factors for S-25(OH)D <50 nmol/l in a population sample of Finnish children. We studied 184 girls and 190 boys aged 6-8 years, analysed S-25(OH)D by chemiluminescence immunoassay and assessed diet quality using 4-d food records and other lifestyle factors by questionnaires. We analysed the determinants of S-25(OH)D using linear regression and risk factors for S-25(OH)D <50 nmol/l using logistic regression. Mean dietary intake of vitamin D was 5.9 (sd 2.1) ug/d. Altogether, 40.8 % of children used no vitamin D supplements. Of all children, 82.4 % did not meet the recommended total vitamin D intake of 10 ug/d. Milk fortified with vitamin D was the main dietary source of vitamin D, providing 48.7 % of daily intake. S-25(OH)D was <50 nmol/l in 19.5 % of children. Consumption of milk products was the main determinant of S-25(OH)D in all children (standardised regression coefficient beta=0.262; P<0.001), girls (beta=0.214; P=0.009) and boys (beta=0.257; P=0.003) in multivariable models. Vitamin D intake from supplements (beta=0.171; P=0.035) and age (beta=-0.198; P=0.015) were associated with S-25(OH)D in girls. Children who drank >=450 g/d of milk, spent >=2.2 h/d in physical activity, had >=13.1 h/d of daylight time or were examined in autumn had reduced risk for S-25(OH)D <50 nmol/l. Insufficient vitamin D intake was common among Finnish children, one-fifth of whom had S 25(OH)D <50 nmol/l. More attention should be paid to the sufficient intake of vitamin D from food and supplements, especially among children who do not use fortified milk products. PMID- 26836318 TI - Chitosan scaffold modified with D-(+) raffinose and enriched with thiol-modified gelatin for improved osteoblast adhesion. AB - The aim of the present study was to investigate whether chitosan-based scaffolds modified with D-(+) raffinose and enriched with thiol-modified gelatin could selectively improve osteoblast adhesion and proliferation. 2, 3 and 4.5% chitosan films were prepared. Chitosan suitability for tissue engineering was confirmed by protein adsorption assay. Scaffolds were incubated with a 2.5 mg ml(-1) BSA solution and the decrease of protein content in the supernatants was measured by spectrophotometry. Chitosan films were then enriched with thiol-modified gelatin and their ability to bind BSA was also measured. Then, 2% chitosan discs with or without thiol-modified gelatin were used as culture substrates for MC3T3-E1 cells. After 72 h cells were stained with trypan blue or with calcein AM and propidium iodide for morphology, viability and proliferation assays. Moreover, cell viability was measured at 48, 72, 96 and 168 h to obtain a growth curve. Chitosan films efficiently bound and retained BSA proportionally to the concentration of chitosan discs. The amount of protein retained was higher on chitosan enriched with thiol-modified gelatin. Moreover, chitosan discs allowed the adhesion and the viability of cells, but inhibited their proliferation. The functionalization of chitosan with thiol-modified gelatin enhanced cell spreading and proliferation. Our data confirm that chitosan is a suitable material for tissue engineering. Moreover, our data show that the enrichment of chitosan with thiol-modified gelatin enhances its biological properties. PMID- 26836319 TI - Fabrication, Characterization, and Biocompatibility of Polymer Cored Reduced Graphene Oxide Nanofibers. AB - Graphene nanofibers have shown a promising potential across a wide spectrum of areas, including biology, energy, and the environment. However, fabrication of graphene nanofibers remains a challenging issue due to the broad size distribution and extremely poor solubility of graphene. Herein, we report a facile yet efficient approach for fabricating a novel class of polymer core reduced graphene oxide shell nanofiber mat (RGO-CSNFM) by direct heat-driven self assembly of graphene oxide sheets onto the surface of electrospun polymeric nanofibers without any requirement of surface treatment. Thus-prepared RGO-CSNFM demonstrated excellent mechanical, electrical, and biocompatible properties. RGO CSNFM also promoted a higher cell anchorage and proliferation of human bone marrow mesenchymal stem cells (hMSCs) compared to the free-standing RGO film without the nanoscale fibrous structure. Further, cell viability of hMSCs was comparable to that on the tissue culture plates (TCPs) with a distinctive healthy morphology, indicating that the nanoscale fibrous architecture plays a critically constructive role in supporting cellular activities. In addition, the RGO-CSNFM exhibited excellent electrical conductivity, making them an ideal candidate for conductive cell culture, biosensing, and tissue engineering applications. These findings could provide a new benchmark for preparing well-defined graphene-based nanomaterial configurations and interfaces for biomedical applications. PMID- 26836320 TI - Pedigree- and SNP-Associated Genetics and Recent Environment are the Major Contributors to Anthropometric and Cardiometabolic Trait Variation. AB - Genome-wide association studies have successfully identified thousands of loci for a range of human complex traits and diseases. The proportion of phenotypic variance explained by significant associations is, however, limited. Given the same dense SNP panels, mixed model analyses capture a greater proportion of phenotypic variance than single SNP analyses but the total is generally still less than the genetic variance estimated from pedigree studies. Combining information from pedigree relationships and SNPs, we examined 16 complex anthropometric and cardiometabolic traits in a Scottish family-based cohort comprising up to 20,000 individuals genotyped for ~520,000 common autosomal SNPs. The inclusion of related individuals provides the opportunity to also estimate the genetic variance associated with pedigree as well as the effects of common family environment. Trait variation was partitioned into SNP-associated and pedigree-associated genetic variation, shared nuclear family environment, shared couple (partner) environment and shared full-sibling environment. Results demonstrate that trait heritabilities vary widely but, on average across traits, SNP-associated and pedigree-associated genetic effects each explain around half the genetic variance. For most traits the recently-shared environment of couples is also significant, accounting for ~11% of the phenotypic variance on average. On the other hand, the environment shared largely in the past by members of a nuclear family or by full-siblings, has a more limited impact. Our findings point to appropriate models to use in future studies as pedigree-associated genetic effects and couple environmental effects have seldom been taken into account in genotype-based analyses. Appropriate description of the trait variation could help understand causes of intra-individual variation and in the detection of contributing loci and environmental factors. PMID- 26836321 TI - Effect of Sexual Arousal on Cortical Coupling During Performance of the Tower of Hanoi Task in Young Men. AB - Sexual arousal affects cognitive processing, which depends on the coordinated functioning among cortical areas. The aim of this research was to determine whether previous observation of videos with sexual content affects the degree of cortical electroencephalographic (EEG) coupling during performance of an executive task. Cortical EEG correlations were calculated in three groups of heterosexual men under three conditions: at rest; during observation of a video with neutral, aggressive, or erotic content; and while performing the Tower of Hanoi task (TOH). Based on self-reports, it was shown that the erotic video induced general and sexual arousal, while the aggressive video affected valence and general arousal. Task performance was similar in all three groups. During performance of TOH, only the erotic group showed a decreased correlation between prefrontal areas with an increased correlation between parietal and prefrontotemporal areas, specifically in the slow bands. It is likely that these changes in the degree of cortical coupling could be associated with the cognitive strategies or functional adaptations that participants require to adequately solve the task during a state of sexual arousal. These data could contribute to improving our understanding of the central nervous mechanisms that underlie the effect of sexual arousal on the cognitive processes involved in tasks like TOH. PMID- 26836323 TI - Reacto-Diffusive Length of N2O5 in Aqueous Sulfate- and Chloride-Containing Aerosol Particles. AB - Heterogeneous reactions of dinitrogen pentoxide (N2O5) on aerosol particles impact air quality and climate, yet aspects of the relevant physical chemistry remain unresolved. One important consideration is the competing effects of diffusion and the rate of chemical reaction within the particle, which determines the length that N2O5 travels within a particle before reacting, referred to as the reacto-diffusive length (l). Large values of l imply a dependence of the reactive uptake efficiency of N2O5, i.e., gamma(N2O5), on particle size. We present measurements of the size dependence of gamma(N2O5) on aqueous sodium chloride, ammonium sulfate, and ammonium bisulfate particles. gamma(N2O5) on ammonium sulfate and ammonium bisulfate particles ranged from 0.016 +/- 0.005 to 0.036 +/- 0.001 as the surface-area-weighted particle radius increased from 39 to 127 nm, resulting in an estimated l of 32 +/- 6 nm. In contrast, gamma(N2O5) on sodium chloride particles was independent of particle size, suggesting a near surface reaction dominated the uptake of N2O5. Differences in the reactivity of the N2O5 intermediate, NO2(+), with water and chloride can explain the observed dependencies. These results allow for parameterizations in atmospheric models to determine a more robust population mean value of gamma(N2O5) that accounts for the distribution of particle sizes. PMID- 26836324 TI - Letter from the Editor. PMID- 26836322 TI - Exercise leads to the re-emergence of the cholinergic/nestin neuronal phenotype within the medial septum/diagonal band and subsequent rescue of both hippocampal ACh efflux and spatial behavior. AB - Exercise has been shown to improve cognitive functioning in a range of species, presumably through an increase in neurotrophins throughout the brain, but in particular the hippocampus. The current study assessed the ability of exercise to restore septohippocampal cholinergic functioning in the pyrithiamine-induced thiamine deficiency (PTD) rat model of the amnestic disorder Korsakoff Syndrome. After voluntary wheel running or sedentary control conditions (stationary wheel attached to the home cage), PTD and control rats were behaviorally tested with concurrent in vivo microdialysis, at one of two time points: 24-h or 2-weeks post exercise. It was found that only after the 2-week adaption period did exercise lead to an interrelated sequence of events in PTD rats that included: (1) restored spatial working memory; (2) rescued behaviorally-stimulated hippocampal acetylcholine efflux; and (3) within the medial septum/diagonal band, the re emergence of the cholinergic (choline acetyltransferase [ChAT+]) phenotype, with the greatest change occurring in the ChAT+/nestin+ neurons. Furthermore, in control rats, exercise followed by a 2-week adaption period improved hippocampal acetylcholine efflux and increased the number of neurons co-expressing the ChAT and nestin phenotype. These findings demonstrate a novel mechanism by which exercise can modulate the mature cholinergic/nestin neuronal phenotype leading to improved neurotransmitter function as well as enhanced learning and memory. PMID- 26836326 TI - Hepatitis A and B screening and vaccination rates among patients with chronic liver disease. AB - Vaccinations against hepatitis A virus (HAV) and hepatitis B virus (HBV) are recommended for patients with chronic liver disease (CLD), yet implementation of these recommendations is lacking. This study reviewed HAV and HBV antibody testing and vaccination status of patients with CLD. In 2008, we began using pre printed liver order sets, which included vaccination options. We compared Scott & White liver clinic CLD patient records from 2005 (238) with patient records from 2008 (792). Screening rates for immunity and vaccination rates of those lacking immunity were calculated. In 2005, 66% of CLD patients were screened for HAV immunity. In 2008, 56% of CLD patients were screened. The HAV vaccination completion rate was 37% in 2005, while in 2008, the rate was 46%. In 2005, 66% of CLD patients were screened for HBV immunity; in 2008, 56 % CLD patients were screened. The HBV vaccination completion rate was 26% in 2005 compared with 36% in 2008. Although there was a lower percentage of screening in 2008, the overall number of patients tripled between 2005 and 2008. There was a significant increase in the total number of patients screened and vaccinated in 2008. Some physicians may have vaccinated their patients without checking for immunity. In January 2008, we implemented pre-printed order sets with checkboxes to help remind providers to order labs to screen for immunity against HAV and HBV and to order vaccinations for those who lacked immunity. The use of these sets may have aided in the increase of vaccination completion rates. PMID- 26836328 TI - Introduction to the special focus on the UK National Immunization Conference 2014. PMID- 26836330 TI - Corrigendum: Rhodium-Catalyzed Asymmetric Synthesis of Spirosilabifluorene Derivatives. PMID- 26836329 TI - Primary vaccine failure to routine vaccines: Why and what to do? AB - There are 2 major factors responsible for vaccine failures, the first is vaccine related such as failures in vaccine attenuation, vaccination regimes or administration. The other is host-related, of which host genetics, immune status, age, health or nutritional status can be associated with primary or secondary vaccine failures. The first describes the inability to respond to primary vaccination, the latter is characterized by a loss of protection after initial effectiveness. Our studies concentrate on the evaluation of immunological characteristics responsible for primary vaccine failures in different (risk) populations for which the underlying mechanisms are currently unknown. Here we summarise current knowledge and findings from our studies. About 2-10% of healthy individuals fail to mount antibody levels to routine vaccines. Comparing the immune responses to different vaccines in non-responder and high-responder vaccinees revealed that hypo-responsiveness is antigen/vaccine-specific at the humoral but not at the cellular level. We found that T-regulatory as well as B regulatory cells and the production of IL-10 are involved in non/hypo responsiveness. Non-responsiveness increases with age and in particular vaccination to a novel vaccine in persons > 65 years is associated with a high low/non-responder rate, indicating that vaccine schedules and doses (at least for primary vaccination) should be adapted according to age. In light of the growing number of allergic but also obese people, our current studies concentrate on these risk groups to reveal whether different vaccination approaches are necessary for optimal protection compared to healthy individuals. These studies are in line with the significant paradigm shift taking place in many fields of medical research and care, and will extend the concept of personalised medicine into the field of vaccinology. PMID- 26836327 TI - Duality at the gate: Skin dendritic cells as mediators of vaccine immunity and tolerance. AB - Since Edward Jenner's discovery that intentional exposure to cowpox could provide lifelong protection from smallpox, vaccinations have been a major focus of medical research. However, while the protective benefits of many vaccines have been successfully translated into the clinic, the cellular and molecular mechanisms that differentiate effective vaccines from sub-optimal ones are not well understood. Dendritic cells (DCs) are the gatekeepers of the immune system, and are ultimately responsible for the generation of adaptive immunity and lifelong protective memory through interactions with T cells. In addition to lymph node and spleen resident DCs, a number of tissue resident DC populations have been identified at barrier tissues, such as the skin, which migrate to the local lymph node (migDC). These populations have unique characteristics, and play a key role in the function of cutaneous vaccinations by shuttling antigen from the vaccination site to the draining lymph node, rapidly capturing freely draining antigens in the lymph node, and providing key stimuli to T cells. However, while migDCs are responsible for the generation of immunity following exposure to certain pathogens and vaccines, recent work has identified a tolerogenic role for migDCs in the steady state as well as during protein immunization. Here, we examine the roles and functions of skin DC populations in the generation of protective immunity, as well as their role as regulators of the immune system. PMID- 26836331 TI - Corrigendum: Evidence for a Boat Conformation at the Transition State of GH76 alpha-1,6-Mannanases--Key Enzymes in Bacterial and Fungal Mannoprotein Metabolism. PMID- 26836332 TI - Corrigendum: Aqueous Sulfate Separation by Crystallization of Sulfate-Water Clusters. PMID- 26836335 TI - In Situ Observation of Successive Crystallizations and Metastable Intermediates in the Formation of Metal-Organic Frameworks. AB - Understanding the driving forces controlling crystallization is essential for the efficient synthesis and design of new materials, particularly metal-organic frameworks (MOFs), where mild solvothermal synthesis often allows access to various phases from the same reagents. Using high-energy in situ synchrotron X ray powder diffraction, we monitor the crystallization of lithium tartrate MOFs, observing the successive crystallization and dissolution of three competing phases in one reaction. By determining rate constants and activation energies, we fully quantify the reaction energy landscape, gaining important predictive power for the choice of reaction conditions. Different reaction rates are explained by the structural relationships between the products and the reactants; larger changes in conformation result in higher activation energies. The methods we demonstrate can easily be applied to other materials, opening the door to a greater understanding of crystallization in general. PMID- 26836334 TI - Reversible pH Switch of Two-Quartet G-Quadruplexes Formed by Human Telomere. AB - A four-repeat human telomere DNA sequence without the 3'-end guanine, d[TAGGG(TTAGGG)2 TTAGG] (htel1-DeltaG23) has been found to adopt two distinct two G-quartet antiparallel basket-type G-quadruplexes, TD and KDH(+) in presence of KCl. NMR, CD, and UV spectroscopy have demonstrated that topology of KDH(+) form is distinctive with unique protonated T18?A20(+) ?G5 base triple and other capping structural elements that provide novel insight into structural polymorphism and heterogeneity of G-quadruplexes in general. Specific stacking interactions amongst two G-quartets flanking base triples and base pairs in TD and KDH(+) forms are reflected in 10 K higher thermal stability of KDH(+) . Populations of TD and KDH(+) forms are controlled by pH. The (de)protonation of A20 is the key for pH driven structural transformation of htel1-DeltaG23. Reversibility offers possibilities for its utilization as a conformational switch within different compartments of living cell enabling specific ligand and protein interactions. PMID- 26836336 TI - No More HF: Teflon-Assisted Ultrafast Removal of Silica to Generate High-Surface Area Mesostructured Carbon for Enhanced CO2 Capture and Supercapacitor Performance. AB - An innovative technique to obtain high-surface-area mesostructured carbon (2545 m(2) g(-1)) with significant microporosity uses Teflon as the silica template removal agent. This method not only shortens synthesis time by combining silica removal and carbonization in a single step, but also assists in ultrafast removal of the template (in 10 min) with complete elimination of toxic HF usage. The obtained carbon material (JNC-1) displays excellent CO2 capture ability (ca. 26.2 wt % at 0 degrees C under 0.88 bar CO2 pressure), which is twice that of CMK-3 obtained by the HF etching method (13.0 wt %). JNC-1 demonstrated higher H2 adsorption capacity (2.8 wt %) compared to CMK-3 (1.2 wt %) at -196 degrees C under 1.0 bar H2 pressure. The bimodal pore architecture of JNC-1 led to superior supercapacitor performance, with a specific capacitance of 292 F g(-1) and 182 F g(-1) at a drain rate of 1 A g(-1) and 50 A g(-1) , respectively, in 1 m H2 SO4 compared to CMK-3 and activated carbon. PMID- 26836337 TI - Oriented Chiral DNA-Silica Film Guided by a Natural Mica Substrate. AB - The formation of highly ordered chiral organic/inorganic films with high density and long-range orientation is important in constructing chiral devices, such as broadband polarization devices, liquid-crystal displays, or negative-reflection materials. A feasible strategy is presented to fabricate three-dimensional mesostructured chiral DNA-silica assemblies into large-scale oriented arrangements. The highly ordered film was aligned by a mica crystal substrate with the bridging effect of suitable divalent metal ions, followed by the growth of the DNA-silica composite by bottom-up assembly with a "quartet templating" method. This simple and effective route would perform well in the alignment and arrangement of highly charged biomolecules, such as polypeptides, proteins, viruses, and their inorganic assemblies, and furthermore could allow the fabrication of chiral optical materials with long-range ordering. PMID- 26836338 TI - Capsule-Capsule Conversion by Guest Encapsulation. AB - Guest-induced M18 L6 -M24 L8 capsule-capsule conversion is reported. Both capsules are composed of Pd(II) ethylenediamine units (M) and 1,3,5-tris(3,5 pyrimidyl)pyrimidine (L), and form trigonal bipyramidal (M18 L6 ) and octahedral (M24 L8) closed-shell structures with huge hydrophobic inner spaces. The M18 L6 trigonal bipyramid is converted to the M24 L8 octahedron through encapsulation of large aromatic guests, with the latter capsule possessing a cavity volume three times larger than the former. Despite the dynamic properties of the capsule host, the encapsulated guests are difficult to extract and are thus isolated from the external environment. PMID- 26836339 TI - How Photoisomerization Drives Peptide Folding and Unfolding: Insights from QM/MM and MM Dynamics Simulations. AB - Photoswitchable azobenzene cross-linkers can control the folding and unfolding of peptides by photoisomerization and can thus regulate peptide affinities and enzyme activities. Using quantum mechanics/molecular mechanics (QM/MM) methods and classical MM force fields, we report the first molecular dynamics simulations of the photoinduced folding and unfolding processes in the azobenzene cross linked FK-11 peptide. We find that the interactions between the peptide and the azobenzene cross-linker are crucial for controlling the evolution of the secondary structure of the peptide and responsible for accelerating the folding and unfolding events. They also modify the photoisomerization mechanism of the azobenzene cross-linker compared with the situation in vacuo or in solution. PMID- 26836340 TI - The [B3(NN)3](+) and [B3(CO)3](+) Complexes Featuring the Smallest pi-Aromatic Species B3(+). AB - We report the spectroscopic identification of the [B3 (NN)3](+) and [B3 (CO)3](+) complexes, which feature the smallest pi-aromatic system B3 (+). A quantum chemical bonding analysis shows that the adducts are mainly stabilized by L->[B3 L2 ](+) sigma-donation. PMID- 26836341 TI - End-to-End Self-Assembly of Semiconductor Nanorods in Water by Using an Amphiphilic Surface Design. AB - One-dimensional (1D) self-assemblies of nanocrystals are of interest because of their vectorial and polymer-like dynamic properties. Herein, we report a simple method to prepare elongated assemblies of semiconductor nanorods (NRs) through end-to-end self-assembly. Short-chained water-soluble thiols were employed as surface ligands for CdSe NRs having a wurtzite crystal structure. The site specific capping of NRs with these ligands rendered the surface of the NRs amphiphilic. The amphiphilic CdSe NRs self-assembled to form elongated wires by end-to-end attachment driven by the hydrophobic effect operating between uncapped NR ends. The end-to-end assembly technique was further applied to CdS NRs and CdSe tetrapods (TPs) with a wurtzite structure. PMID- 26836343 TI - Bioconjugating Thiols to Poly(acrylamide) Gels for Cell Culture Using Methylsulfonyl Co-monomers. AB - Poly(acrylamide) P(AAm) gels have become relevant model substrates to study cell response to the mechanical and biochemical properties of the cellular microenvironment. However, current bioconjugation strategies to functionalize P(AAm) gels, mainly using photoinduced arylazide coupling, show poor specificity and hinder conclusive studies of material properties and cellular responses. We describe methylsulfonyl-containing P(AAm) hydrogels for cell culture. These gels allow easy, specific and functional covalent coupling of thiol containing bioligands in tunable concentrations under physiological conditions, while retaining the same swelling, porosity, cytocompatibility, and low protein adsorption of P(AAm) gels. These materials allow quantitative and standardized studies of cell-materials interactions with P(AAm) gels. PMID- 26836342 TI - ATP-Releasing Nucleotides: Linking DNA Synthesis to Luciferase Signaling. AB - A new strategy is reported for the production of luminescence signals from DNA synthesis through the use of chimeric nucleoside tetraphosphate dimers in which ATP, rather than pyrophosphate, is the leaving group. ATP-releasing nucleotides (ARNs) were synthesized as derivatives of the four canonical nucleotides. All four derivatives are good substrates for DNA polymerase, with Km values averaging 13-fold higher than those of natural dNTPs, and kcat values within 1.5-fold of those of native nucleotides. Importantly, ARNs were found to yield very little background signal with luciferase. DNA synthesis experiments show that the ATP byproduct can be harnessed to elicit a chemiluminescence signal in the presence of luciferase. When using a polymerase together with the chimeric nucleotides, target DNAs/RNAs trigger the release of stoichiometrically large quantities of ATP, thereby allowing sensitive isothermal luminescence detection of nucleic acids as diverse as phage DNAs and short miRNAs. PMID- 26836345 TI - Electronic Structure of Copper Corroles. AB - The ground state electronic structure of copper corroles has been a topic of debate and revision since the advent of corrole chemistry. Computational studies formulate neutral Cu corroles with an antiferromagnetically coupled Cu(II) corrole radical cation ground state. X-ray photoelectron spectroscopy, EPR, and magnetometry support this assignment. For comparison, Cu(II) isocorrole and [TBA][Cu(CF3)4] were studied as authentic Cu(II) and Cu(III) samples, respectively. In addition, the one-electron reduction and one-electron oxidation processes are both ligand-based, demonstrating that the Cu(II) centre is retained in these derivatives. These observations underscore ligand non-innocence in copper corrole complexes. PMID- 26836344 TI - Synthesis of Iron Nanometallic Glasses and Their Application in Cancer Therapy by a Localized Fenton Reaction. AB - Metallic glasses and cancer theranostics are emerging fields that do not seem to be related to each other. Herein, we report the facile synthesis of amorphous iron nanoparticles (AFeNPs) and their superior physicochemical properties compared to their crystalline counterpart, iron nanocrystals (FeNCs). The AFeNPs can be used for cancer theranostics by inducing a Fenton reaction in the tumor by taking advantage of the mild acidity and the overproduced H2 O2 in a tumor microenvironment: Ionization of the AFeNPs enables on-demand ferrous ion release in the tumor, and subsequent H2 O2 disproportionation leads to efficient (.)OH generation. The endogenous stimuli-responsive (.)OH generation in the presence AFeNPs enables a highly specific cancer therapy without the need for external energy input. PMID- 26836347 TI - P,S Ligands for the Asymmetric Construction of Quaternary Stereocenters in Palladium-Catalyzed Decarboxylative [4+2] Cycloadditions. AB - A new hybrid P,S ligand was exploited by combining a chiral beta-amino sulfide and a simple diphenyl phosphite. The resultant ligand performs extremely well in a palladium-catalyzed asymmetric decarboxylative [4+2] cycloaddition reaction, thus generating multiple contiguous stereocenters and a chiral quaternary center. By doing so, a straightforward route to highly functionalized tetrahydroquinolines was developed with yields of up to 99 %, as well as 98 % ee and greater than 95:5 d.r. Moreover, mechanistic insights into this transformation and the possible stereocontrol are discussed. PMID- 26836346 TI - Intermolecular Electronic Coupling of Organic Units for Efficient Persistent Room Temperature Phosphorescence. AB - Although persistent room-temperature phosphorescence (RTP) emission has been observed for a few pure crystalline organic molecules, there is no consistent mechanism and no universal design strategy for organic persistent RTP (pRTP) materials. A new mechanism for pRTP is presented, based on combining the advantages of different excited-state configurations in coupled intermolecular units, which may be applicable to a wide range of organic molecules. By following this mechanism, we have developed a successful design strategy to obtain bright pRTP by utilizing a heavy halogen atom to further increase the intersystem crossing rate of the coupled units. RTP with a remarkably long lifetime of 0.28 s and a very high quantum efficiency of 5 % was thus obtained under ambient conditions. This strategy represents an important step in the understanding of organic pRTP emission. PMID- 26836349 TI - Conformational Slippage Determines Rotational Frequency in Five-Component Nanorotors. AB - Several five-component nanorotors ROT-3 that rotate at different rates were prepared by adding phenanthrolines of distinct lateral size as brake blocks to the four-component nanorotor ROT-2. The brake blocks interfere with the 180 degrees rotor causing the rotational frequency to drop from 97 kHz to 5 kHz. The effect of the rotating brake blocks on the rotational frequency in ROT-3 is accurately predicted by a nanomechanical model called "conformational slippage". For quantification, the interaction of the brake blocks with the trajectory of the main rotator is gauged based on the number of interfering vs. non-interfering conformations as computed by PM6. PMID- 26836348 TI - Direct Catalytic Synthesis of Unprotected 2-Amino-1-Phenylethanols from Alkenes by Using Iron(II) Phthalocyanine. AB - Aryl-substituted amino alcohols are privileged scaffolds in medicinal chemistry and natural products. Herein, we report that an exceptionally simple and inexpensive Fe(II) complex efficiently catalyzes the direct transformation of simple alkenes into unprotected amino alcohols in good yield and perfect regioselectivity. This new catalytic method was applied in the expedient synthesis of bioactive molecules and could be extended to aminoetherification. PMID- 26836350 TI - Microbial transformations in phosphonate biosynthesis and catabolism, and their importance in nutrient cycling. AB - Phosphorus cycling in the biosphere has traditionally been thought to involve almost exclusively transformations of the element in its pentavalent oxidation state. Recent evidence, however, suggests that a significant fraction of environmental phosphorus may exist in a more reduced form. Most abundant of these reduced phosphorus compounds are the phosphonates, with their direct carbon phosphorus bonds, and striking progress has recently been made in elucidating the biochemistry of microbial phosphonate transformations. These advances are now presented in the context of their contribution to our understanding of phosphorus biogeochemistry and of such diverse fields as the productivity of the oceans, marine methanogenesis and the discovery of novel microbial antimetabolites. PMID- 26836351 TI - Comparison of Errors Using Two Length-Based Tape Systems for Prehospital Care in Children. AB - BACKGROUND: The use of a length/weight-based tape (LBT) for equipment size and drug dosing for pediatric patients is recommended in a joint statement by multiple national organizations. A new system, known as HandtevyTM, allows for rapid determination of critical drug doses without performing calculations. OBJECTIVE: To compare two LBT systems for dosing errors and time to medication administration in simulated prehospital scenarios. METHODS: This was a prospective randomized trial comparing the Broselow Pediatric Emergency TapeTM (Broselow) and Handtevy LBTTM (Handtevy). Paramedics performed 2 pediatric simulations: cardiac arrest with epinephrine administration and hypoglycemia mandating dextrose. Each scenario was repeated utilizing both systems with a 1 year-old and 5-year-old size manikin. Facilitators recorded identified errors and time points of critical actions including time to medication. RESULTS: We enrolled 80 paramedics, performing 320 simulations. For Dextrose, there were significantly more errors with Broselow (63.8%) compared to Handtevy (13.8%) and time to administration was longer with the Broselow system (220 seconds vs. 173 seconds). For epinephrine, the LBTs were similar in overall error rate (Broselow 21.3% vs. Handtevy 16.3%) and time to administration (89 vs. 91 seconds). Cognitive errors were more frequent when using the Broselow compared to Handtevy, particularly with dextrose administration. The frequency of procedural errors was similar between the two LBT systems. CONCLUSION: In simulated prehospital scenarios, use of the Handtevy LBT system resulted in fewer errors for dextrose administration compared to the Broselow LBT, with similar time to administration and accuracy of epinephrine administration. PMID- 26836352 TI - Differential contribution of visual and auditory information to accurately predict the direction and rotational motion of a visual stimulus. AB - Vision and auditory information are critical for perception and to enhance the ability of an individual to respond accurately to a stimulus. However, it is unknown whether visual and auditory information contribute differentially to identify the direction and rotational motion of the stimulus. The purpose of this study was to determine the ability of an individual to accurately predict the direction and rotational motion of the stimulus based on visual and auditory information. In this study, we recruited 9 expert table-tennis players and used table-tennis service as our experimental model. Participants watched recorded services with different levels of visual and auditory information. The goal was to anticipate the direction of the service (left or right) and the rotational motion of service (topspin, sidespin, or cut). We recorded their responses and quantified the following outcomes: (i) directional accuracy and (ii) rotational motion accuracy. The response accuracy was the accurate predictions relative to the total number of trials. The ability of the participants to predict the direction of the service accurately increased with additional visual information but not with auditory information. In contrast, the ability of the participants to predict the rotational motion of the service accurately increased with the addition of auditory information to visual information but not with additional visual information alone. In conclusion, this finding demonstrates that visual information enhances the ability of an individual to accurately predict the direction of the stimulus, whereas additional auditory information enhances the ability of an individual to accurately predict the rotational motion of stimulus. PMID- 26836361 TI - Chemokine ligand 7 (CCL7) and innate immune cells in psoriasis: beyond redundancy. PMID- 26836362 TI - 13C solid-state NMR analysis of the most common pharmaceutical excipients used in solid drug formulations Part II: CP kinetics and relaxation analysis. AB - Excipients used in the solid drug formulations differ in their NMR relaxation and (13)C cross-polarization (CP) kinetics parameters. Therefore, experimental parameters like contact time of cross-polarization and repetition time have a major impact on the registered solid state NMR spectra and in consequence on the results of the NMR analysis. In this work the CP kinetics and relaxation of the most common pharmaceutical excipients: anhydrous alpha-lactose, alpha-lactose monohydrate, mannitol, sucrose, sorbitol, sodium starch glycolate type A and B, starch of different origin, microcrystalline cellulose, hypromellose, ethylcellulose, methylcellulose, hydroxyethylcellulose, sodium alginate, magnesium stearate, sodium laurilsulfate and Kollidon((r)) were analyzed. The studied excipients differ significantly in their optimum repetition time (from 5 s to 1200 s) and T(1rho)(I) parameters (from 2 ms to 73 ms). The practical use of those differences in the excipients composition analysis was demonstrated on the example of commercially available tablets containing indapamide as an API. The information presented in this article will help to choose the correct acquisition parameters and also will save the time and effort needed for their optimization in the NMR analysis of the solid drug formulations. PMID- 26836363 TI - Hydrolysed egg displays strong decrease in allergenicity and is well tolerated by egg-allergic patients. AB - Food allergies are believed to be on the rise, and currently, management relies on the avoidance of the food. Hen's egg allergy is after cow's milk allergy the most common food allergy; eggs are used in many food products and thus difficult to avoid. A technological process using a combination of enzymatic hydrolysis and heat treatment was designed to produce modified hen's egg with reduced allergenic potential. Biochemical (SDS-PAGE, Size exclusion chromatography and LC-MS/MS) and immunological (ELISA, immunoblot, RBL-assays, animal model) analysis showed a clear decrease in intact proteins as well as a strong decrease of allergenicity. In a clinical study, 22 of the 24 patients with a confirmed egg allergy who underwent a double-blind food challenge with the hydrolysed egg remained completely free of symptoms. Hydrolysed egg products may be beneficial as low allergenic foods for egg-allergic patients to extent their diet. PMID- 26836364 TI - Optimization by Molecular Fine Tuning of Dihydro-beta-agarofuran Sesquiterpenoids as Reversers of P-Glycoprotein-Mediated Multidrug Resistance. AB - P-glycoprotein (P-gp) plays a crucial role in the development of multidrug resistance (MDR), a major obstacle for successful chemotherapy in cancer. Herein, we report on the development of a natural-product-based library of 81 dihydro beta-agarofuran sesquiterpenes (2-82) by optimization of the lead compound 1. The compound library was evaluated for its ability to inhibit P-gp-mediated daunomycin efflux in MDR cells. Selected analogues were further analyzed for their P-gp inhibition constant, intrinsic toxicity, and potency to reverse daunomycin and vinblastine resistances. Analogues 6, 24, 28, 59, and 66 were identified as having higher potency than compound 1 and verapamil, a first generation P-gp modulator. SAR analysis revealed the size of the aliphatic chains and presence of nitrogen atoms are important structural characteristics to modulate reversal activity. The present study highlights the potential of these analogues as modulators of P-gp mediated MDR in cancer cells. PMID- 26836365 TI - The effect of fetal sex on customized fetal growth charts. AB - OBJECTIVE: To evaluate the effect of fetal sex on singleton pregnancy growth charts customized for parental characteristics, race, and parity Methods: In a multicentric cross-sectional study, 8070 ultrasonographic examinations from low risk singleton pregnancies between 16 and 40 weeks of gestation were considered. The fetal measurements obtained were biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL). Quantile regression was used to examine the impact of fetal sex across the biometric percentiles of the fetal measurements considered together with parents' height, weight, parity, and race. RESULTS: Fetal gender resulted to be a significant covariate for BDP, HC, and AC with higher values for male fetuses (p <= 0.0009). Minimal differences were found among sexes for FL. Parity, maternal race, paternal height and maternal height, and weight resulted significantly related to the fetal biometric parameters considered independently from fetal gender. CONCLUSION: In this study, we constructed customized biometric growth charts for fetal sex, parental, and obstetrical characteristics using quantile regression. The use of gender-specific charts offers the advantage to define individualized normal ranges of fetal biometric parameters at each specific centile. This approach may improve the antenatal identification of abnormal fetal growth. PMID- 26836366 TI - "Thunderstruck": Plasma-Polymer-Coated Porous Silicon Microparticles As a Controlled Drug Delivery System. AB - Controlling the release kinetics from a drug carrier is crucial to maintain a drug's therapeutic window. We report the use of biodegradable porous silicon microparticles (pSi MPs) loaded with the anticancer drug camphothecin, followed by a plasma polymer overcoating using a loudspeaker plasma reactor. Homogenous "Teflon-like" coatings were achieved by tumbling the particles by playing AC/DC's song "Thunderstruck". The overcoating resulted in a markedly slower release of the cytotoxic drug, and this effect correlated positively with the plasma polymer coating times, ranging from 2-fold up to more than 100-fold. Ultimately, upon characterizing and verifying pSi MP production, loading, and coating with analytical methods such as time-of-flight secondary ion mass spectrometry, scanning electron microscopy, thermal gravimetry, water contact angle measurements, and fluorescence microscopy, human neuroblastoma cells were challenged with pSi MPs in an in vitro assay, revealing a significant time delay in cell death onset. PMID- 26836367 TI - Visible-Light-Mediated Synthesis of Amides from Aldehydes and Amines via in Situ Acid Chloride Formation. AB - An efficient visible-light photocatalysis-based one-pot amide synthesis method was developed; visible-light irradiation of a mixture of an aldehyde, tert-butyl hydrogen peroxide, and N-chlorosuccinimide using a Ru(bpy)3Cl2 photocatalyst afforded an acid chloride, which subsequently reacted with amine to yield the corresponding amide. The reaction was used to synthesize moclobemide and a D3 receptor intermediate. PMID- 26836368 TI - Improving the solubility of dexlansoprazole by cocrystallization with isonicotinamide. AB - Cocrystallization of an active pharmaceutical ingredient (API) with a cocrystal former (co-former) is widely used to tailor the physicochemical properties of parent APIs. For proton-pump inhibitors (PPIs), the isolation of cocrystals has not been widely investigated. Here, a 1:1 cocrystal of a PPI molecule, dexlansoprazole (DLS), was obtained by solvent crystallization with isonicotinamide (INM). The product was characterized by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), solid-state and liquid NMR, as well as Fourier transform infrared spectroscopy (FTIR) techniques. A two-point R2(2)(9) hetero-synthon was proposed to exist in the cocrystal, where intermolecular hydrogen bonding occurs between NH, SO groups of DLS and amide of INM. The dissolution profiles of DLS and DLS-INM in water were also collected, and the results demonstrate the cocrystal exhibits superior apparent maximum solubility relative to the pure drug. PMID- 26836369 TI - Longitudinal associations of friend-based social support and PTSD symptomatology during a cannabis cessation attempt. AB - Research supports bidirectional associations between social support and posttraumatic stress disorder (PTSD), whereby social support may buffer against PTSD, and individuals with PTSD may experience decreasing support over time. Research examining contexts that may affect these relations is needed. This study examined the longitudinal associations between PTSD and social support from friends over a 6-month period in 116 veterans with cannabis dependence who had recently initiated an attempt to quit cannabis use. A cross-lagged autoregressive model revealed a significant, negative relation between earlier PTSD symptoms and later support. An exploratory multigroup analysis comparing those with and without a relapse in the first month after their quit attempt revealed that the significant negative association between PTSD and future support was present only in those who relapsed. Although this analysis was limited by a small sample size, results suggest that substance use may be an influential contextual variable that impacts the longitudinal associations between PTSD and support. PMID- 26836370 TI - The effects of social anxiety on interpersonal evaluations of warmth and dominance. AB - Social anxiety disorder is associated with interpersonal dysfunction, but it is not clear why people with the disorder feel unsatisfied with their relationships. One possibility is that higher social anxiety could lead to changes in sensitivity to interpersonal traits. We examined whether social anxiety moderates the types of interpersonal evaluations people make regarding warmth and dominance. We developed vignettes in which central characters systematically varied in dominance and warmth and asked two samples of participants (undergraduate students, n=176, and online workers, n=403) to rate their willingness to interact with, and the social desirability of, these characters. Participants in general reported stronger desire to interact with warmer and less dominant characters, and rated warmer and more dominant characters as being more socially desirable. People with higher social anxiety exhibited greater tolerance for colder and more submissive characters on both rated dimensions. The perceived similarity of the characters accounted for the bulk of these effects. Participants indicated a higher desire to interact with characters more similar to themselves, and people with higher social anxiety were more likely to rate submissive and cold characters as being like themselves. The results have implications for clinical interventions for social anxiety disorder. PMID- 26836371 TI - Escape Mutations, Ganciclovir Resistance, and Teratoma Formation in Human iPSCs Expressing an HSVtk Suicide Gene. AB - Human pluripotent stem cells (hPSCs) hold great promise for cell therapy. However, a major concern is the risk of tumor formation by residual undifferentiated cells contaminating the hPSC-derived cell product. Suicide genes could safeguard against such adverse events by enabling elimination of cells gone astray, but the efficacy of this approach has not yet been thoroughly tested. Here, we engineered a lentivirally encoded herpes simplex virus thymidine kinase (HSVtk) with expression restricted to undifferentiated hPSCs through regulation by the let7 family of miRNAs. We show that induced pluripotent stem cells (iPSCs) expressing a let7-regulated HSVtk transgene are selectively killed by ganciclovir (GCV), whereas differentiated cells are fully protected. However, in contrast to previous studies, we find that in vivo GCV administration results in longer latency but does not prevent teratoma formation by iPSCs expressing either a constitutive or a let7-regulated HSVtk, without evidence of silencing of the HSVtk. Clonal analyses of iPSCs expressing HSVtk revealed frequent emergence of GCV resistance which, at least in some cases, could be attributed to preexisting inactivating mutations in the HSVtk coding sequence, selected for upon GCV treatment. Our findings have important consequences for the future use of suicide genes in hPSC-based cell therapies. PMID- 26836373 TI - Bisecting Microfluidic Channels with Metallic Nanowires Fabricated by Nanoskiving. AB - This paper describes the fabrication of millimeter-long gold nanowires that bisect the center of microfluidic channels. We fabricated the nanowires by nanoskiving and then suspended them over a trench in a glass structure. The channel was sealed by bonding it to a complementary poly(dimethylsiloxane) structure. The resulting structures place the nanowires in the region of highest flow, as opposed to the walls, where it approaches zero, and expose their entire surface area to fluid. We demonstrate active functionality, by constructing a hot wire anemometer to measure flow through determining the change in resistance of the nanowire as a function of heat dissipation at low voltage (<5 V). Further, passive functionality is demonstrated by visualizing individual, fluorescently labeled DNA molecules attached to the wires. We measure rates of flow and show that, compared to surface-bound DNA strands, elongation saturates at lower rates of flow and background fluorescence from nonspecific binding is reduced. PMID- 26836372 TI - MicroRNA-27b Enhances the Hepatic Regenerative Properties of Adipose-Derived Mesenchymal Stem Cells. AB - Adipose-derived mesenchymal stem cells (ASCs) are readily available multipotent mesenchymal progenitor cells and have become an attractive therapeutic tool for regenerative medicine. We herein investigated the mechanistic role of how miR-27b modulated regenerative capacities of ASCs. Intravenous administration of miR-27b transfected ASCs (ASCs-miR-27b) was conducted after 70% partial hepatectomy (PH). After PH, rats injected with ASCs-miR-27b had decreased inflammatory cytokines and increased hepatocyte growth factor and other related growth factors. We showed that the nature of ASCs-miR-27b to inhibit hepatic stellate cell activation was dependent upon peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1alpha) in vitro. Moreover, expression of miR-27b in ASCs induced heme oxygenase-1 (HO-1), resulting in increased production of ATP, protective cytokines/growth factors, and genes involved in mitochondrial biogenesis in a PGC-1alpha-dependent manner. RNA sequencing (RNA-Seq) analysis revealed drastic transcriptional changes in livers treated with ASCs-miR-27b after PH. The differentially expressed genes classified into "regeneration," "fibrosis," and "mitochondrial biogenesis" clusters were mainly mitochondrial. The potential biological context reflecting the effects of PGC-1alpha by ASCs-miR 27b treatment was also observed by the subnetwork analysis with HO-1 and PGC 1alpha being the top-ranked regulatory genes. We demonstrate autologous ASCs-miR 27b enhances liver regeneration and, importantly, preserves hepatic function through paracrine actions which offers a viable therapeutic option to facilitate rapid recovery after liver injury. PMID- 26836374 TI - Diagnosis and management of latent tuberculosis. AB - PURPOSE OF REVIEW: Latent tuberculosis infection (LTBI) may affect over two billion individuals and serves as a potential reservoir for future active tuberculosis. The identification and treatment of LTBI in those at highest risk for progression is an essential part of tuberculosis control. RECENT FINDINGS: Interferon-gamma release assays are increasingly used for targeted testing and diagnosis of latent disease. The performance of these immunodiagnostic tests has been studied in various groups and may be better than the tuberculin skin test in certain populations. Ongoing research is focused on new biomarkers that may diagnose LTBI or predict progression to active tuberculosis. Isoniazid preventive treatment is effective at reducing risk of active disease, but length of treatment and potential side-effects limit patient acceptance and compliance. Rifamycin-based regimens are increasingly studied as a shorter and perhaps less toxic alternative for preventive therapy. SUMMARY: Identification of those with LTBI is important as it allows treatment of those at highest risk of progression to active disease and thus decreases the overall burden of tuberculosis. The development of new immunodiagnostics may further improve identification of those at risk and alternative medication regimens may increase compliance with and efficacy of preventive therapy. PMID- 26836375 TI - Macrolide therapy of pneumonia: is it necessary, and how does it help? AB - PURPOSE OF REVIEW: An update and literature review assessing the implications for use of macrolide therapy for patients with pneumonia is very relevant. Multiple studies have focused on assessing the efficacy, clinical effectiveness and clinical risks associated with the use of macrolides. RECENT FINDINGS: The scope of this review is on recently published literature regarding the use of macrolides in patients with pneumonia. Recent evidence suggests that macrolides may benefit several populations of patients with pneumonia that includes ambulatory care, hospitalized patients with nonsevere pneumonia and severe pneumonia patients requiring ICU admission. In addition, there is benefit among patients with pneumococcal pneumonia, particularly those patients hospitalized with severe disease. The contradictory results that emerged from recent randomized controlled trials testing the efficacy of macrolide are discussed. Important remarks are made to the risks of cardiovascular events related to the use of macrolides and the clinical implications for care. SUMMARY: A careful decision on the use of macrolides in patients with pneumonia will need to balance the possible beneficial effects and the risks linked to their use. PMID- 26836376 TI - Practical concept of pharmacokinetics/pharmacodynamics in the management of skin and soft tissue infections. AB - PURPOSE OF REVIEW: This article gives an overview of the practical concept of pharmacokinetic/pharmacodynamic principles useful for clinicians in the management of skin and soft tissue infections (SSTIs). RECENT FINDINGS: Recent studies suggest that distinguishing between bacteriostatic or bactericidal activity when choosing an antimicrobial for the treatment of severe infections could probably be clinically irrelevant. Conversely, what could help clinicians in maximizing the therapeutic efficacy of the various drugs in routine practice is taking care of some pharmacokinetic/pharmacodynamic principles. Concentration dependent agents may exhibit more rapid bacterial killing than observed with time dependent agents. Serum concentrations may not always adequately predict tissue exposure in patients with SSTIs, and measuring concentrations at the infection site is preferable. Hydrophilic antimicrobials showed generally lower penetration rates than the lipophilic ones and might require alternative dosing approaches in the presence of severe sepsis or septic shock. Conversely, tissue penetration of lipophilic antimicrobials is often unaffected by the pathophysiological status. Real-time therapeutic drug monitoring may be a very helpful tool for optimizing therapy of severe infections. SUMMARY: Taking care of pharmacokinetic/pharmacodynamic principles deriving from the most recent findings may help clinicians in maximizing treatment of SSTIs with antimicrobials in every situation. PMID- 26836377 TI - Administrative Databases in Orthopaedic Research: Pearls and Pitfalls of Big Data. AB - The drive for evidence-based decision-making has highlighted the shortcomings of traditional orthopaedic literature. Although high-quality, prospective, randomized studies in surgery are the benchmark in orthopaedic literature, they are often limited by size, scope, cost, time, and ethical concerns and may not be generalizable to larger populations. Given these restrictions, there is a growing trend toward the use of large administrative databases to investigate orthopaedic outcomes. These datasets afford the opportunity to identify a large numbers of patients across a broad spectrum of comorbidities, providing information regarding disparities in care and outcomes, preoperative risk stratification parameters for perioperative morbidity and mortality, and national epidemiologic rates and trends. Although there is power in these databases in terms of their impact, potential problems include administrative data that are at risk of clerical inaccuracies, recording bias secondary to financial incentives, temporal changes in billing codes, a lack of numerous clinically relevant variables and orthopaedic-specific outcomes, and the absolute requirement of an experienced epidemiologist and/or statistician when evaluating results and controlling for confounders. Despite these drawbacks, administrative database studies are fundamental and powerful tools in assessing outcomes on a national scale and will likely be of substantial assistance in the future of orthopaedic research. PMID- 26836378 TI - Structural Characterization of Thermochromic and Spin Equilibria in Solid-State Ni(detu)4Cl2 (detu = N,N'-Diethylthiourea). AB - Consecutive thermochromic lattice distortional and spin crossover equilibria in solid-state Ni(detu)4Cl2 (detu = N,N'-diethylthiourea) are investigated by variable-temperature X-ray crystallography (173-333 K), DFT calculations, and differential scanning calorimetry. Thermochromism and anomalous magnetism were reported previously (S. L. Holt, Jr., et al. J. Am. Chem. Soc. 1964, 86, 519 520); the latter was attributed to equilibration of a singlet ground state and a thermally accessible triplet state, but structural data were not obtained. A crystal structure at 173(2) K revealed [Ni(detu)4](2+) centers with distorted planar ligation of nickel(II) to the four sulfur atoms, with an average Ni-S bond length of 2.226(3) A. The nickel ion was displaced out-of-plane by 0.334 A toward a proximal apical chloride at a nonbonding distance of 3.134(1) A. Asymmetry in the trans S-Ni-S angles was coupled to a monoclinic <-> tetragonal lattice distortion (T(1/2) = 254 +/- 11 K), resulting in thermochromism. Spin crossover occurs by tetragonal modulation of nickel(II) with approach of the proximal chloride at higher temperatures (T(1/2) = 383 +/- 18 K), which is consistent with a contraction of -0.096(4) A in the Ni...Cl separation observed at 293 K. A high spin (S = 1) square-pyramidal [Ni(dmtu)4Cl](+) model (dmtu = N,N' dimethylthiourea) was optimized by DFT calculations, which estimated limiting equatorial Ni-S bond lengths of 2.45 A and an apical Ni-Cl bond of 2.43 A. Electronic spectra of the spin isomers were calculated by TD-DFT methods. Assignment of the FTIR spectrum was assisted by frequency calculations and isotope substitution. PMID- 26836379 TI - Balloon anchoring intraluminal tracking technique: a new application of an old technique for coronary artery chronic total occlusion percutaneous intervention. PMID- 26836380 TI - 'Lithuanian' Mutation Finally Found in Lithuania. PMID- 26836381 TI - Cat Bite: An Unusual Cause of Foot Drop. PMID- 26836382 TI - Mesenteric Thrombosis Complicating Influenza B Infection. PMID- 26836383 TI - An Alternative Way to Provide Healthcare for Veterans. PMID- 26836384 TI - Using Science to Battle Stigma in Addressing the Opioid Epidemic: Opioid Agonist Therapy Saves Lives. PMID- 26836385 TI - Screening Asymptomatic Cardiac Sarcoidosis: Role of Cardiac MRI. PMID- 26836386 TI - Gastroparesis Concurrent with Adult Cystic Fibrosis; Are They Related? PMID- 26836388 TI - A Novel Diagnostic Approach for Evaluating Suspected Coronary Artery Disease. PMID- 26836387 TI - Transient Hyponatremia During Hospitalization for Acute Heart Failure. AB - OBJECTIVE: The objective was to study whether the temporal pattern of transient hyponatremia development in acute heart failure might provide insight into its pathophysiology and prognostic relevance. METHODS: A post hoc analysis of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) and Diuretic Optimization Strategies Evaluation in Acute Heart Failure (DOSE AHF) studies was performed (n = 716). Patients were stratified according to the temporal pattern of hyponatremia development: (1) no hyponatremia, (2) persistent hyponatremia, (3) decompensation hyponatremia disappearing with decongestive treatment, and (4) treatment-induced hyponatremia. RESULTS: Transient decompensation versus no hyponatremia was associated with significantly elevated blood urea nitrogen/creatinine ratio (P < .001), plasma renin activity (P < .001), and plasma aldosterone levels (P < .001) at baseline. Disease severity characteristics of such patients were intermediate between no and persistent hyponatremia. In contrast, patients with treatment-induced versus no hyponatremia had similar baseline characteristics and comparable natriuretic peptide levels, and both groups had little neurohumoral activation at baseline. Diuretic efficacy, defined as net fluid balance (milliliters) per 40 mg furosemide-equivalent dose administered, was lower in patients with persistent or treatment-induced hyponatremia versus decompensation hyponatremia or no hyponatremia, respectively. The former versus latter groups also had more pronounced neurohumoral activation with decongestive treatment. The risk for all cause mortality (hazard ratio, 2.50; 95% confidence interval, 1.50-4.19; P < .001) and death or heart failure readmission (hazard ratio, 2.18; 95% confidence interval, 1.60-2.97; P < .001) was significantly elevated in patients with persistent versus no hyponatremia, with the risk of decompensation and treatment hyponatremia situated in between. CONCLUSIONS: Transient hyponatremia is prognostically relevant, but it has a heterogeneous cause according to its temporal pattern of development. PMID- 26836390 TI - Resistance to change and resurgence in humans engaging in a computer task. AB - The relation between persistence, as measured by resistance to change, and resurgence has been examined with nonhuman animals but not systematically with humans. The present study examined persistence and resurgence with undergraduate students engaging in a computer task for points exchangeable for money. In Phase 1, a target response was maintained on a multiple variable-interval (VI) 15-s (Rich) VI 60-s (Lean) schedule of reinforcement. In Phase 2, the target response was extinguished while an alternative response was reinforced at equal rates in both schedule components. In Phase 3, the target and the alternative responses were extinguished. In an additional test of persistence (Phase 4), target responding was reestablished as in Phase 1 and then disrupted by access to videos in both schedule components. In Phases 2 and 4, target responding was more persistent in the Rich than in the Lean component. Also, resurgence generally was greater in the Rich than in the Lean component in Phase 3. The present findings with humans extend the generality of those obtained with nonhuman animals showing that higher reinforcement rates produce both greater persistence and resurgence, and suggest that common processes underlie response persistence and relapse. PMID- 26836389 TI - High Uric Acid Induces Insulin Resistance in Cardiomyocytes In Vitro and In Vivo. AB - Clinical studies have shown hyperuricemia strongly associated with insulin resistance as well as cardiovascular disease. Direct evidence of how high uric acid (HUA) affects insulin resistance in cardiomyocytes, but the pathological mechanism of HUA associated with cardiovascular disease remains to be clarified. We aimed to examine the effect of HUA on insulin sensitivity in cardiomyocytes and on insulin resistance in hyperuricemic mouse model. We exposed primary cardiomyocytes and a rat cardiomyocyte cell line, H9c2 cardiomyocytes, to HUA, then quantified glucose uptake with a fluorescent glucose analog, 2-NBDG, after insulin challenge and detected reactive oxygen species (ROS) production. Western blot analysis was used to examine the levels of insulin receptor (IR), phosphorylated insulin receptor substrate 1 (IRS1, Ser307) and phospho-Akt (Ser473). We monitored the impact of HUA on insulin resistance, insulin signaling and IR, phospho-IRS1 (Ser307) and phospho-Akt levels in myocardial tissue of an acute hyperuricemia mouse model established by potassium oxonate treatment. HUA inhibited insulin-induced glucose uptake in H9c2 and primary cardiomyocytes. It increased ROS production; pretreatment with N-acetyl-L-cysteine (NAC), a ROS scavenger, reversed HUA-inhibited glucose uptake induced by insulin. HUA exposure directly increased the phospho-IRS1 (Ser307) response to insulin and inhibited that of phospho-Akt in H9C2 cardiomyocytes, which was blocked by NAC. Furthermore, the acute hyperuricemic mice model showed impaired glucose tolerance and insulin tolerance accompanied by increased phospho-IRS1 (Ser307) and inhibited phospho-Akt response to insulin in myocardial tissues. HUA inhibited insulin signaling and induced insulin resistance in cardiomyocytes in vitro and in vivo, which is a novel potential mechanism of hyperuricemic-related cardiovascular disease. PMID- 26836391 TI - Can early protein restriction induce the development of binge eating? AB - We tested the hypothesis that perinatal undernourishment is a factor for binge eating. At 52 days rats born from dams fed on 17% protein (Control) or 8% protein (Undernourished) were distributed into four groups, two of which continued to be fed ad libitum chow and two were submitted to three consecutive Restricted/Refeeding (R/R) cycles. According to the following schedule: Control Naive (from mothers fed 17% protein/no restriction phase); Control Restricted (from mothers fed 17% protein/restriction phase); Undernourished Naive (from mothers fed 8% protein/no restriction phase); and Undernourished Restricted (from mothers fed 8% protein/restriction phase). Each cycle consisted of a restriction phase (in the first four days 40% of the mean daily individual chow intake was offered for consumption), followed by a refeeding phase (4 days of chow ad libitum). After the three cycles, all animals were subjected to a feeding test (chow diet and palatable food ad libitum for 24h). During the feeding test, the Undernourished Restricted demonstrated rebound hyperphagia during 2, 4 and 6h. These results suggest the perinatal undernourishment cannot contribute to a binge eating phenotype. PMID- 26836392 TI - Predicting Outcomes after Minimally Percutaneous Nephrolithotomy with the Aid of a Patented System by Using the Guy's Stone Score. AB - OBJECTIVES: At present, there is no report on the application of Guy's stone (GS) score in minimally invasive percutaneous nephrolithotomy (MPCNL). We therefore investigate the clinical effect of MPCNL by using a patented irrigation and clearance system according to the GS. METHODS: A total of 222 consecutive patients were divided into 2 groups that were treated with MPCNL using the patented system or standard PCNL using Electro Medical System (EMS) ultrasound/ballistic trajectory lithotripsy and clearance system, respectively (124 patients in patented system group, 98 patients in EMS system group). The stone complexity and severity of complications were stratified by GS and Modified Clavien grading system in this study, respectively. The success and complication rates between MPCNL and PCNL were compared. RESULTS: The patented system group had a significantly higher success rate (GS3: 95 vs. 43% and GS4: 67 vs. 31%) and a significantly less complications rate (GS3: 12 vs. 27% and GS4: 21 vs. 46%) in GS3 and GS4 compared with the EMS system group. Also, the patented system had significant lower complication rates in Clavien grades II-IV than that of the EMS system. CONCLUSION: The MPCNL using the patented irrigation and clearance system was more efficient in dealing with renal stones of high complexity (GS3-4). PMID- 26836393 TI - Comparison of the Estimated Glomerular Filtration Rate (eGFR) in Diabetic Patients, Non-Diabetic Patients and Living Kidney Donors. AB - BACKGROUND/AIMS: We have reported that the eGFR overestimates renal function when glycemic control is poor. It has been reported that eGFR calculated by serum creatinine underestimates GFR in living kidney donors. We compared the utility of the eGFR in diabetic patients, non-diabetic patients and living kidney donors. Forty diabetic patients, 40 non-diabetic patients, and 40 living kidney donors were enrolled. METHODS: GFR was measured by inulin clearance (C(in)). eGFR was calculated based on serum creatinine (eGFR(cr)) or serum cystatin C (eGFR(cys)). We compared the agreements between each of the eGFR and C(in) in each group. RESULTS: There were significant and positive correlations between each eGFR and C(in) in diabetic patients and non-diabetic patients. However, the intraclass correlation coefficients (ICC) between each eGFR and C(in) in diabetic patients (ICC: eGFR(cr) 0.699, eGFR(cys) 0.604) were weaker than those in non-diabetic patients (ICC: eGFR(cr) 0.865, eGFR(cys) 0.803). The correlation coefficients between each eGFR and C(in) (eGFR(cr); r = 0.422, p = 0.0067 and eGFR(cys); r = 0.358, p = 0.0522) in living kidney donors were significantly weaker than those in non-diabetic patients. The ICCs between each eGFR and C(in) (ICC: eGFR(cr) 0.340, eGFR(cys) 0.345) in living kidney donors were significantly weaker than those in non-diabetic patients. CONCLUSIONS: Based on C(in), eGFR was accurate in non-diabetic patients. However, eGFR was inaccurate in living kidney donors and relatively inaccurate in diabetic patients. PMID- 26836394 TI - Maximum likelihood positioning and energy correction for scintillation detectors. AB - An algorithm for determining the crystal pixel and the gamma ray energy with scintillation detectors for PET is presented. The algorithm uses Likelihood Maximisation (ML) and therefore is inherently robust to missing data caused by defect or paralysed photo detector pixels. We tested the algorithm on a highly integrated MRI compatible small animal PET insert. The scintillation detector blocks of the PET gantry were built with the newly developed digital Silicon Photomultiplier (SiPM) technology from Philips Digital Photon Counting and LYSO pixel arrays with a pitch of 1 mm and length of 12 mm. Light sharing was used to readout the scintillation light from the 30 * 30 scintillator pixel array with an 8 * 8 SiPM array. For the performance evaluation of the proposed algorithm, we measured the scanner's spatial resolution, energy resolution, singles and prompt count rate performance, and image noise. These values were compared to corresponding values obtained with Center of Gravity (CoG) based positioning methods for different scintillation light trigger thresholds and also for different energy windows. While all positioning algorithms showed similar spatial resolution, a clear advantage for the ML method was observed when comparing the PET scanner's overall single and prompt detection efficiency, image noise, and energy resolution to the CoG based methods. Further, ML positioning reduces the dependence of image quality on scanner configuration parameters and was the only method that allowed achieving highest energy resolution, count rate performance and spatial resolution at the same time. PMID- 26836395 TI - Validation of Force Fields of Rubber through Glass-Transition Temperature Calculation by Microsecond Atomic-Scale Molecular Dynamics Simulation. AB - Microsecond atomic-scale molecular dynamics simulation has been employed to calculate the glass-transition temperature (Tg) of cis- and trans-1,4 polybutadiene (PB) and 1,4-polyisoprene (PI). Both all-atomistic and united-atom models have been simulated using force fields, already available in literature. The accuracy of these decade old force fields has been tested by comparing calculated glass-transition temperatures to the corresponding experimental values. Tg depicts the phase transition in elastomers and substantially affects various physical properties of polymers, and hence the reproducibility of Tg becomes very crucial from a thermodynamic point of view. Such validation using Tg also evaluates the ability of these force fields to be used for advanced materials like rubber nanocomposites, where Tg is greatly affected by the presence of fillers. We have calculated Tg for a total of eight systems, featuring all-atom and united-atom models of cis- and trans-PI and -PB, which are the major constituents of natural and synthetic rubber. Tuning and refinement of the force fields has also been done using quantum-chemical calculations to obtain desirable density and Tg. Thus, a set of properly validated force fields, capable of reproducing various macroscopic properties of rubber, has been provided. A novel polymer equilibration protocol, involving potential energy convergence as the equilibration criterion, has been proposed. We demonstrate that not only macroscopic polymer properties like density, thermal expansion coefficient, and Tg but also local structural characteristics like end-to-end distance (R) and radius of gyration (Rg) and mechanical properties like bulk modulus have also been equilibrated using our strategy. Complete decay of end-to-end vector autocorrelation function with time also supports proper equilibration using our strategy. PMID- 26836396 TI - Fatal presumed tiger snake (Notechis scutatus) envenomation in a cat with measurement of venom and antivenom concentration. AB - A fatal outcome of a presumed tiger snake (Notechis scutatus) envenomation in a cat is described. Detectable venom components and antivenom concentrations in serum from clotted and centrifuged whole blood and urine were measured using a sensitive and specific ELISA. The cat presented in a paralysed state with a markedly elevated serum CK but with normal clotting times. The cat was treated with intravenous fluids and received two vials of equine whole IgG bivalent (tiger and brown snake) antivenom. Despite treatment the cat's condition did not improve and it died 36 h post-presentation. Serum concentration of detectable tiger snake venom components at initial presentation was 311 ng/mL and urine 832 ng/mL, this declined to non-detectable levels in serum 15-min after intravenous antivenom. Urine concentration of detectable tiger snake venom components declined to 22 ng/mL at post-mortem. Measurement of equine anti-tiger snake venom specific antibody demonstrated a concentration of 7.2 Units/mL in serum at post mortem which had declined from an initial high of 13 Units/mL at 15-min post antivenom. The ELISA data demonstrated the complete clearance of detectable venom components from serum with no recurrence in the post-mortem samples. Antivenom concentrations in serum at initial presentation were at least 100-fold higher than theoretically required to neutralise the circulating concentrations of venom. Despite the fatal outcome in this case it was concluded that this was unlikely that is was due to insufficient antivenom. PMID- 26836398 TI - Corrigendum. AB - This corrects the article: Steven G. Potkin, Tatsuya Kimura and John Guarino. A 6 week, double-blind, placebo- and haloperidol-controlled, phase II study of lurasidone in patients with acute schizophrenia. Therapeutic Advances in Psychopharmacology 2045125315606027, first published on October 9, 2015. Doi:10.1177/2045125315606027. PMID- 26836397 TI - Molecular inflation, attrition and the rule of five. AB - Physicochemical properties underlie all aspects of drug action and are critical for solubility, permeability and successful formulation. Specific physicochemical properties shown to be relevant to oral drugs are size, lipophilicity, ionisation, hydrogen bonding, polarity, aromaticity and shape. The rule of 5 (Ro5) and subsequent studies have raised awareness of the importance of compound quality amongst bioactive molecules. Lipophilicity, probably the most important physical property of oral drugs, has on average changed little over time in oral drugs, until increases in drugs published after 1990. In contrast other molecular properties such as average size have increased significantly. Factors influencing property inflation include the targets pursued, where antivirals frequently violate the Ro5, risk/benefit considerations, and variable drug discovery practices. The compounds published in patents from the pharmaceutical industry are on average larger, more lipophilic and less complex than marketed oral drugs. The variation between individual companies' patented compounds is due to different practices and not to the targets pursued. Overall, there is demonstrable physical property attrition in moving from patents to candidate drugs to marketed drugs. The pharmaceutical industry's recent poor productivity has been due, in part, to progression of molecules that are unable to unambiguously test clinical efficacy, and attrition can therefore be improved by ensuring candidate drug quality is 'fit for purpose.' The combined ligand efficiency (LE) and lipophilic ligand efficiency (LLE) values of many marketed drugs are optimised relative to other molecules acting at the same target. Application of LLE in optimisation can help identify improved leads, even with challenging targets that seem to require lipophilic ligands. Because of their targets, some projects may need to pursue 'beyond Ro5' physicochemical space; such projects will require non-standard lead generation and optimisation and should not dominate in a well-balanced portfolio. Compound quality is controllable by lead selection and optimisation and should not be a cause of clinical failure. PMID- 26836399 TI - Palladium-Catalyzed Cyclization of Alkenes with Organohalides. AB - A palladium-catalyzed tandem C-Br/C-H functionalization and cyclization of alkenes with organohalides is reported. This reaction provides an operationally simple method for the synthesis of various fluorene, pyrroloindole, and benzoxazine derivatives, which are useful pharmaceutical framework and photoelectronic devices. Two new C-C/O bonds, a quaternary carbon center and a new ring, are simultaneously formed in this one-pot reaction. PMID- 26836400 TI - Constitutional abnormalities of chromosome 21 predispose to iAMP21-acute lymphoblastic leukaemia. AB - In addition to Down syndrome, individuals with other constitutional abnormalities of chromosome 21 have an increased risk of developing childhood acute lymphoblastic leukaemia (ALL). Specifically, carriers of the Robertsonian translocation between chromosomes 15 and 21, rob(15;21) (q10; q10)c, have ~2,700 increased risk of developing ALL with iAMP21 (intrachromosomal amplification of chromosome 21). In these patients, chromosome 15 as well as chromosome 21 is involved in the formation of iAMP21, referred to here as der(21)(15;21). Individuals with constitutional ring chromosomes involving chromosome 21, r(21)c, are also predisposed to iAMP21-ALL, involving the same series of mutational processes as seen in sporadic- and der(21)(15;21)-iAMP21 ALL. Evidence is accumulating that the dicentric nature of the Robertsonian and ring chromosome is the initiating factor in the formation of the complex iAMP21 structure. Unravelling these intriguing predispositions to iAMP21-ALL may provide insight into how other complex rearrangements arise in cancer. PMID- 26836401 TI - Perspective-taking behavior as the probabilistic weighing of multiple domains. AB - Our starting point is the apparently-contradictory results in the psycholinguistic literature regarding whether, when interpreting a definite referring expressions, listeners process relative to the common ground from the earliest moments of processing. We propose that referring expressions are not interpreted relative solely to the common ground or solely to one's Private (or egocentric) knowledge, but rather reflect the simultaneous integration of the two perspectives. We implement this proposal in a Bayesian model of reference resolution, focusing on the model's predictions for two prior studies: Keysar, Barr, Balin, and Brauner (2000) and Heller, Grodner and Tanenhaus (2008). We test the model's predictions in a visual-world eye-tracking experiment, demonstrating that the original results cannot simply be attributed to different perspective taking strategies, and showing how they can arise from the same perspective taking behavior. PMID- 26836403 TI - The representational-hierarchical view of pattern separation: Not just hippocampus, not just space, not just memory? AB - Pattern separation (PS) has been defined as a process of reducing overlap between similar input patterns to minimize interference amongst stored representations. The present article describes this putative PS process from the "representational hierarchical" perspective (R-H), which uses a hierarchical continuum instead of a cognitive modular processing framework to describe the organization of the ventral visual perirhinal-hippocampal processing stream. Instead of trying to map psychological constructs onto anatomical modules in the brain, the R-H model suggests that the function of brain regions depends upon what representations they contain. We begin by discussing a main principle of the R-H framework, the resolution of "ambiguity" of lower level representations via the formation of unique conjunctive representations in higher level areas, and how this process is remarkably similar to definitions of PS. Work from several species and experimental approaches suggest that this principle of resolution of ambiguity via conjunctive representations has considerable explanatory power, leads to wide possibilities for experimentation, and also supports some perhaps surprising conclusions. PMID- 26836404 TI - Ovarian follicle development in vitro and oocyte competence: advances and challenges for farm animals. AB - During the last 2 decades, research on in vitro preantral follicle growth and oocyte maturation has delivered fascinating advances concerning the knowledge of processes regulating follicle growth and the developmental competence of oocytes. These advances include (1) information about the role of several hormones and growth factors on in vitro activation of primordial follicles; (2) increased understanding of the intracellular pathway involved in the initiation of primordial follicle growth; (3) the growth of primary and secondary follicles up to antral stages; and (4) production of embryos from oocytes from in vitro grown preantral follicles. This review article describes these advances, especially in regard farm animals, and discusses the reasons that limit embryo production from oocytes derived from preantral follicles cultured in vitro. PMID- 26836402 TI - Quantitative Measurement of Histone Tail Acetylation Reveals Stage-Specific Regulation and Response to Environmental Changes during Drosophila Development. AB - Histone modification plays a major role in regulating gene transcription and ensuring the healthy development of an organism. Numerous studies have suggested that histones are dynamically modified during developmental events to control gene expression levels in a temporal and spatial manner. However, the study of histone acetylation dynamics using currently available techniques is hindered by the difficulty of simultaneously measuring acetylation of the numerous potential sites of modification present in histones. Here, we present a methodology that allows us to combine mass spectrometry-based histone analysis with Drosophila developmental genetics. Using this system, we characterized histone acetylation patterns during multiple developmental stages of the fly. Additionally, we utilized this analysis to characterize how treatments with pharmacological agents or environmental changes such as gamma-irradiation altered histone acetylation patterns. Strikingly, gamma-irradiation dramatically increased the level of acetylation at H3K18, a site linked to DNA repair via nonhomologous end joining. In mutant fly strains deficient in DNA repair proteins, however, this increase in the level of H3K18 acetylation was lost. These results demonstrate the efficacy of our combined mass spectrometry system with a Drosophila model system and provide interesting insight into the changes in histone acetylation during development, as well as the effects of both pharmacological and environmental agents on global histone acetylation. PMID- 26836405 TI - Climate change vulnerability, adaptation and risk perceptions at farm level in Punjab, Pakistan. AB - Pakistan is among the countries highly exposed and vulnerable to climate change. The country has experienced many severe floods, droughts and storms over the last decades. However, little research has focused on the investigation of vulnerability and adaptation to climate-related risks in Pakistan. Against this backdrop, this article investigates the farm level risk perceptions and different aspects of vulnerability to climate change including sensitivity and adaptive capacity at farm level in Pakistan. We interviewed a total of 450 farming households through structured questionnaires in three districts of Punjab province of Pakistan. This study identified a number of climate-related risks perceived by farm households such as extreme temperature events, insect attacks, animal diseases and crop pests. Limited water availability, high levels of poverty and a weak role of local government in providing proper infrastructure were the factors that make farmers more sensitive to climate-related risks. Uncertainty or reduction in crop and livestock yields; changed cropping calendars and water shortage were the major adverse impacts of climate-related risks reported by farmers in the study districts. Better crop production was reported as the only positive effect. Further, this study identified a number of farm level adaptation methods employed by farm households that include changes in crop variety, crop types, planting dates and input mix, depending upon the nature of the climate-related risks. Lack of resources, limited information, lack of finances and institutional support were some constraints that limit the adaptive capacity of farm households. This study also reveals a positive role of cooperation and negative role of conflict in the adaptation process. The study suggests to address the constraints to adaptation and to improve farm level cooperation through extended outreach and distribution of institutional services, particularly climate-specific farm advisory services. PMID- 26836406 TI - Analysis of Protein Sumoylation. AB - Sumoylation, wherein small ubiquitin-like modifier (SUMO) proteins are covalently attached to specific lysine residues of target proteins, plays an important role in regulating many diverse cellular processes via its control of the functional properties of the modified proteins. Identification of new sumoylated proteins is expected to expand understanding of the role this modification has in cell function. This unit describes two different assays for determining whether a particular protein is sumoylated: the first method employs immunoprecipitation of the protein followed by SUMO immunoblot. The second involves incubating the protein (either an in vitro translation product or a purified recombinant protein) with a reconstituted in vitro sumoylation reaction followed by examination for increased molecular-weight bands in SDS-PAGE as sumoylated forms of the protein. Either of these approaches can also be used to determine the sumoylated lysine residue(s) by comparing modification of the normal protein versus lysine-to-arginine substitutions of potential sumoylation sites, which once determined allows analysis of the effect of sumoylation on the protein's function. PMID- 26836407 TI - Handling Metalloproteinases. AB - Substrate cleavage by metalloproteinases involves nucleophilic attack on the scissile peptide bond by a water molecule that is polarized by a catalytic metal, usually a zinc ion, and a general base, usually the carboxyl group of a glutamic acid side chain. The zinc ion is most often complexed by imidazole nitrogens of histidine side chains. This arrangement suggests that the physiological pH optimum of most metalloproteinases is in the neutral range. In addition to their catalytic metal ion, many metalloproteinases contain additional transition metal or alkaline earth ions, which are structurally important or modulate the catalytic activity. As a consequence, these enzymes are generally sensitive to metal chelators. Moreover, the catalytic metal can be displaced by adventitious metal ions from buffers or biological fluids, which may fundamentally alter the catalytic function. Therefore, handling, purification, and assaying of metalloproteinases require specific precautions to warrant their stability. PMID- 26836409 TI - Expression, Solubilization, and Purification of Bacterial Membrane Proteins. AB - Bacterial integral membrane proteins play many important roles, including sensing changes in the environment, transporting molecules into and out of the cell, and in the case of commensal or pathogenic bacteria, interacting with the host organism. Working with membrane proteins in the lab can be more challenging than working with soluble proteins because of difficulties in their recombinant expression and purification. This protocol describes a standard method to express, solubilize, and purify bacterial integral membrane proteins. The recombinant protein of interest with a 6His affinity tag is expressed in E. coli. After harvesting the cultures and isolating cellular membranes, mild detergents are used to solubilize the membrane proteins. Protein-detergent complexes are then purified using IMAC column chromatography. Support protocols are included to help select a detergent for protein solubilization and for use of gel filtration chromatography for further purification. PMID- 26836408 TI - Reactivation of Aggregated Proteins by the ClpB/DnaK Bi-Chaperone System. AB - Protein aggregation is a common problem in protein biochemistry and is linked to many cellular pathologies and human diseases. The molecular chaperone ClpB can resolubilize and reactivate aggregated proteins. This unit describes the procedure for following reactivation of an aggregated enzyme glucose-6-phosphate dehydrogenase mediated by ClpB from Escherichia coli in cooperation with another molecular chaperone, DnaK. The procedures for purification of these chaperones are also described. PMID- 26836410 TI - Selective Precipitation of Proteins. AB - Selective precipitation of proteins can be used as a bulk method to recover the majority of proteins from a crude lysate, as a selective method to fractionate a subset of proteins from a protein solution, or as a very specific method to recover a single protein of interest from a purification step. This unit describes a number of methods suitable for selective precipitation. In each of the protocols that are outlined, the physical or chemical basis of the precipitation process, the parameters that can be varied for optimization, and the basic steps for developing an optimized precipitation are described. PMID- 26836411 TI - Reaction mechanisms for on-surface synthesis of covalent nanostructures. AB - In recent years, on-surface synthesis has become an increasingly popular strategy to form covalent nanostructures. The approach has great prospects for facilitating the manufacture of a range of fascinating materials with atomic precision. However, the on-surface reactions are enigmatic to control, currently restricting its bright perspectives and there is a great need to explore how the reactions are governed. The objective of this topical review is to summarize theoretical work that has focused on comprehending on-surface synthesis protocols through studies of reaction mechanisms. PMID- 26836413 TI - A high-risk group of pregnant women with elevated levels of conflict-related trauma, intimate partner violence, symptoms of depression and other forms of mental distress in post-conflict Timor-Leste. AB - Women in low-income, post-conflict (LI-PC) [Corrected] countries are at risk of exposure to the traumatic events (TEs) of war and intimate partner violence (IPV), forms of stress that are known to lead to depression and other adverse mental health outcomes. We aimed to assess an index of exposure to these two forms of trauma to identify pregnant women attending antenatal clinics in conflict-affected Timor-Leste at high risk of depression and other forms of stress. A large, cross-sectional study of women in the second trimester of pregnancy was conducted in the four main government antenatal clinics in Dili district of Timor-Leste, between May 2014, and January 2015. The sample consisted of 1672 consecutive women, 3 to 6 months pregnant, with a response rate of 96%. We applied the Edinburgh Postnatal Depression Scale, the Kessler-10 psychological distress scale and the Harvard Trauma Questionnaire. IPV was assessed by the World Health Organisation measure. Composite categories of conflict-related TEs and severity of IPV showed a dose-response relationship with depressive symptoms: for exposure to four or more conflict-related TEs and severe psychological IPV, the adjusted odds ratio (AOR) was 3.95 (95% confidence interval (CI) 2.10-7.40); for four or more TEs and physical abuse, AOR 8.16 (95% CI 3.53-18.85); and for four or more TEs and severe psychological and physical abuse, AOR 9.78 (95% CI 5.31-18.02). For any mental distress, the AOR for four or more TEs and severe psychological abuse was 3.60 (95% CI 2.08-6.23); for four or more TEs and physical abuse 7.03 (95% CI 3.23-15.29); and for four or more TEs and severe psychological and physical abuse the AOR was 10.45 (95% CI 6.06-18.01). Of 184 women (11% of the sample) who reported ? 4 TEs and either physical abuse alone or in combination with severe psychological abuse, 78 (42%) reached threshold for depressive symptoms and 93 (51%) for any mental distress, a 10-fold increase in depressive and other mental health symptoms. Priority should be directed to providing urgent mental health and social interventions for this group of women. Our findings offer a framework for a tiered approach to detection, guiding prevention and intervention strategies for IPV and associated mental health problems in low-income post-conflict countries. PMID- 26836412 TI - Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia. AB - Evidence suggests that microRNA-137 (miR-137) is involved in the genetic basis of schizophrenia. Risk variants within the miR-137 host gene (MIR137HG) influence structural and functional brain-imaging measures, and miR-137 itself is predicted to regulate hundreds of genes. We evaluated the influence of a MIR137HG risk variant (rs1625579) in combination with variants in miR-137-regulated genes TCF4, PTGS2, MAPK1 and MAPK3 on gray matter concentration (GMC). These genes were selected based on our previous work assessing schizophrenia risk within possible miR-137-regulated gene sets using the same cohort of subjects. A genetic risk score (GRS) was determined based on genotypes of these four schizophrenia risk associated genes in 221 Caucasian subjects (89 schizophrenia patients and 132 controls). The effects of the rs1625579 genotype with the GRS of miR-137 regulated genes in a three-way interaction with diagnosis on GMC patterns were assessed using a multivariate analysis. We found that schizophrenia subjects homozygous for the MIR137HG risk allele show significant decreases in occipital, parietal and temporal lobe GMC with increasing miR-137-regulated GRS, whereas those carrying the protective minor allele show significant increases in GMC with GRS. No correlations of GMC and GRS were found in control subjects. Variants within or upstream of genes regulated by miR-137 in combination with the MIR137HG risk variant may influence GMC in schizophrenia-related regions in patients. Given that the genes evaluated here are involved in protein kinase A signaling, dysregulation of this pathway through alterations in miR-137 biogenesis may underlie the gray matter loss seen in the disease. PMID- 26836414 TI - MAP training: combining meditation and aerobic exercise reduces depression and rumination while enhancing synchronized brain activity. AB - Mental and physical (MAP) training is a novel clinical intervention that combines mental training through meditation and physical training through aerobic exercise. The intervention was translated from neuroscientific studies indicating that MAP training increases neurogenesis in the adult brain. Each session consisted of 30 min of focused-attention (FA) meditation and 30 min of moderate intensity aerobic exercise. Fifty-two participants completed the 8-week intervention, which consisted of two sessions per week. Following the intervention, individuals with major depressive disorder (MDD; n=22) reported significantly less depressive symptoms and ruminative thoughts. Typical healthy individuals (n=30) also reported less depressive symptoms at follow-up. Behavioral and event-related potential indices of cognitive control were collected at baseline and follow-up during a modified flanker task. Following MAP training, N2 and P3 component amplitudes increased relative to baseline, especially among individuals with MDD. These data indicate enhanced neural responses during the detection and resolution of conflicting stimuli. Although previous research has supported the individual beneficial effects of aerobic exercise and meditation for depression, these findings indicate that a combination of the two may be particularly effective in increasing cognitive control processes and decreasing ruminative thought patterns. PMID- 26836415 TI - Neuroplasticity in response to cognitive behavior therapy for social anxiety disorder. AB - Patients with anxiety disorders exhibit excessive neural reactivity in the amygdala, which can be normalized by effective treatment like cognitive behavior therapy (CBT). Mechanisms underlying the brain's adaptation to anxiolytic treatments are likely related both to structural plasticity and functional response alterations, but multimodal neuroimaging studies addressing structure function interactions are currently missing. Here, we examined treatment-related changes in brain structure (gray matter (GM) volume) and function (blood-oxygen level dependent, BOLD response to self-referential criticism) in 26 participants with social anxiety disorder randomly assigned either to CBT or an attention bias modification control treatment. Also, 26 matched healthy controls were included. Significant time * treatment interactions were found in the amygdala with decreases both in GM volume (family-wise error (FWE) corrected P(FWE) = 0.02) and BOLD responsivity (P(FWE) = 0.01) after successful CBT. Before treatment, amygdala GM volume correlated positively with anticipatory speech anxiety (P(FWE)=0.04), and CBT-induced reduction of amygdala GM volume (pre-post) correlated positively with reduced anticipatory anxiety after treatment (P(FWE) ? 0.05). In addition, we observed greater amygdala neural responsivity to self referential criticism in socially anxious participants, as compared with controls (P(FWE) = 0.029), before but not after CBT. Further analysis indicated that diminished amygdala GM volume mediated the relationship between decreased neural responsivity and reduced social anxiety after treatment (P=0.007). Thus, our results suggest that improvement-related structural plasticity impacts neural responsiveness within the amygdala, which could be essential for achieving anxiety reduction with CBT. PMID- 26836416 TI - Exome sequencing in dementia with Lewy bodies. AB - Dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia. Siblings of affected individuals are at greater risk of developing DLB, but little is known about the underlying genetic basis of the disease. We set out to determine whether mutations in known highly penetrant neurodegenerative disease genes are found in patients with DLB. Whole-exome sequencing was performed on 91 neuropathologically confirmed cases of DLB, supplemented by independent APOE genotyping. Genetic variants were classified using established criteria, and additional neuropathological examination was performed for putative mutation carriers. Likely pathogenic variants previously described as causing monogenic forms of neurodegenerative disease were found in 4.4% of patients with DLB. The APOE E4 allele increased the risk of disease (P=0.0001), conferred a shorter disease duration (P=0.043) and earlier age of death (P=0.0015). In conclusion, although known pathogenic mutations in neurodegenerative disease genes are uncommon in DLB, known genetic risk factors are present in >60% of cases. APOE E4 not only modifies disease risk, but also modulates the rate of disease progression. The reduced penetrance of reported pathogenic alleles explains the lack of a family history in most patients, and the presence of variants previously described as causing frontotemporal dementia suggests a mechanistic overlap between DLB and other neurodegenerative diseases. PMID- 26836419 TI - Abstracts from ATTD 2016 9th International Conference on Advanced Technologies & Treatments for Diabetes Milan, Italy-February 3-6, 2016. PMID- 26836417 TI - Short environmental enrichment in adulthood reverses anxiety and basolateral amygdala hypertrophy induced by maternal separation. AB - Maternal separation during early childhood results in greater sensitivity to stressors later in adult life. This is reflected as greater propensity to develop stress-related disorders in humans and animal models, including anxiety and depression. Environmental enrichment (EE) reverses some of the damaging effects of maternal separation in rodent models when provided during peripubescent life, temporally proximal to the separation. It is presently unknown if EE provided outside this critical window can still rescue separation-induced anxiety and neural plasticity. In this report we use a rat model to demonstrate that a single short episode of EE in adulthood reduced anxiety-like behaviour in maternally separated rats. We further show that maternal separation resulted in hypertrophy of dendrites and increase in spine density of basolateral amygdala neurons in adulthood, long after initial stress treatment. This is congruent with prior observations showing centrality of basolateral amygdala hypertrophy in anxiety induced by stress during adulthood. In line with the ability of the adult enrichment to rescue stress-induced anxiety, we show that enrichment renormalized stress-induced structural expansion of the amygdala neurons. These observations argue that behavioural plasticity induced by early adversity can be rescued by environmental interventions much later in life, likely mediated by ameliorating effects of enrichment on basolateral amygdala plasticity. PMID- 26836418 TI - Validity and Reliability of the Golombok Rust Inventory of Sexual Satisfaction in Couples with Incontinent Partners. AB - There is currently no published information on the validity and reliability of the Golombok Rust Inventory of Sexual Satisfaction in the Asian population, specifically in patients with stress urinary incontinence, which limits its use in this region. Our study aimed to evaluate the psychometric properties of this questionnaire in the Malaysian population. Ten couples were recruited for the pilot testing. The agreement between the English and Chinese or Malay versions were tested using the intraclass correlation coefficients, with results of more than 0.80 for all subscales and overall scores indicating good agreement. Sixty six couples were included in the subsequent phase. The following data are presented in the order of English, Chinese, and Malay. Cronbach's alphas for the male total score were 0.82, 0.88, and 0.95. For the female total score, Cronbach's alphas were 0.76, 0.78, and 0.88. Intraclass correlation coefficients for the male total score were 0.93, 0.94, and 0.99, while intraclass correlation coefficients for the female total score were 0.89, 0.86, and 0.88. In conclusion, the English, Chinese, and Malay versions each proved to be valid and reliable in our Malaysian population. PMID- 26836421 TI - DTT: 18 Years and Counting... PMID- 26836422 TI - Continuous Glucose Monitoring in 2015. PMID- 26836423 TI - Diabetes Technology and the Human Factor. PMID- 26836425 TI - Technologies in Diabetes--the Seventh ATTD Yearbook. PMID- 26836426 TI - Insulin Pumps. PMID- 26836427 TI - Closing the Loop. PMID- 26836428 TI - Self-Monitoring of Blood Glucose. PMID- 26836429 TI - New Insulins, Biosimilars, and Insulin Therapy. PMID- 26836430 TI - Using Digital Health Technology to Prevent and Treat Diabetes. PMID- 26836431 TI - Immune Intervention in Type 1 Diabetes. PMID- 26836432 TI - Advances in Exercise, Physical Activity, and Diabetes Mellitus. PMID- 26836433 TI - Diabetes Technology and Therapy in the Pediatric Age Group. PMID- 26836434 TI - Grey matter brain injuries are common in Ugandan children with cerebral palsy suggesting a perinatal aetiology in full-term infants. AB - AIM: There is limited literature on brain imaging studies of children with cerebral palsy (CP) in low and middle income countries. We investigated neuroimaging patterns of children with CP attending a tertiary referral centre in Uganda to determine how they differed from studies reported from high income countries and their relationship with prenatal and postnatal factors. METHODS: Precontrast and postcontrast computed tomography (CT) scans of 78 CP children aged 2-12 years were conducted using a Philips MX 16-slice CT scanner. Two radiologists, blinded to the patient's clinical status, independently reviewed the scans. RESULTS: Abnormal CT scans were detected in 69% of the children sampled, with very few having primary white matter injuries (4%). Primary grey matter injuries (PGMI) (44%) and normal scans (31%) were most frequent. Children with a history of hospital admission following birth were three times more likely to have PGMI (odds ratio [OR] 2.8; 95% CI 1.1-7.1), suggesting a perinatal period with medical complications. CONCLUSION: Brain imaging patterns in this group of CP children differed markedly from imaging studies reported from high income countries, suggesting a perinatal aetiology in full-term infants and reduced survival in preterm infants. PMID- 26836435 TI - Effect of Removal of Planned Parenthood from the Texas Women's Health Program. AB - BACKGROUND: Texas is one of several states that have barred Planned Parenthood affiliates from providing health care services with the use of public funds. After the federal government refused to allow (and courts blocked) the exclusion of Planned Parenthood affiliates from the Texas Medicaid fee-for-service family planning program, Texas excluded them from a state-funded replacement program, effective January 1, 2013. We assessed rates of contraceptive-method provision, method continuation through the program, and childbirth covered by Medicaid before and after the Planned Parenthood exclusion. METHODS: We used all program claims from 2011 through 2014 to examine changes in the number of claims for contraceptives according to method for 2 years before and 2 years after the exclusion. Among women using injectable contraceptives at baseline, we observed rates of contraceptive continuation through the program and of childbirth covered by Medicaid. We used the difference-in-differences method to compare outcomes in counties with Planned Parenthood affiliates with outcomes in those without such affiliates. RESULTS: After the Planned Parenthood exclusion, there were estimated reductions in the number of claims from 1042 to 672 (relative reduction, 35.5%) for long-acting, reversible contraceptives and from 6832 to 4708 (relative reduction, 31.1%) for injectable contraceptives (P<0.001 for both comparisons). There was no significant change in the number of claims for short-acting hormonal contraceptive methods during this period. Among women using injectable contraceptives, the percentage of women who returned for a subsequent on-time contraceptive injection decreased from 56.9% among those whose subsequent injections were due before the exclusion to 37.7% among those whose subsequent injections were due after the exclusion in the counties with Planned Parenthood affiliates but increased from 54.9% to 58.5% in the counties without such affiliates (estimated difference in differences in counties with affiliates as compared with those without affiliates, -22.9 percentage points; P<0.001). During this period in counties with Planned Parenthood affiliates, the rate of childbirth covered by Medicaid increased by 1.9 percentage points (a relative increase of 27.1% from baseline) within 18 months after the claim (P=0.01). CONCLUSIONS: The exclusion of Planned Parenthood affiliates from a state-funded replacement for a Medicaid fee-for-service program in Texas was associated with adverse changes in the provision of contraception. For women using injectable contraceptives, there was a reduction in the rate of contraceptive continuation and an increase in the rate of childbirth covered by Medicaid. (Funded by the Susan T. Buffett Foundation.). PMID- 26836436 TI - Freewheeling sisters cause problems. AB - The factors that lead to errors in chromosome segregation during the production of egg cells in humans are becoming clearer. PMID- 26836437 TI - Broadcasting Not Properly: Using B-type Natriuretic Peptide Interval Likelihood Ratios and the Results of Other Emergency Department Tests to Diagnose Acute Heart Failure in Dyspneic Patients. PMID- 26836438 TI - Cobalt(III)-Catalyzed Redox-Neutral Synthesis of Unprotected Indoles Featuring an N-N Bond Cleavage. AB - A redox-neutral cobalt(III)-catalyzed synthetic approach for the direct synthesis of unprotected indoles showcasing an N-N bond cleavage is reported. The herein newly introduced Boc-protected hydrazines establish a beneficial addition to the limited portfolio of oxidizing directing groups for cobalt(III) catalysis. Moreover, the developed catalytic methodology tolerates a good variety of functional groups. PMID- 26836439 TI - Synergistic Inhibition of Enamel Demineralization by Peptide 8DSS and Fluoride. AB - The biomimetic peptide 8DSS has shown beneficial effects in promoting remineralization of demineralized enamel in vitro. Here we examined the ability of 8DSS alone and in combination with fluoride to inhibit enamel demineralization during pH-cycling mimicking intraoral conditions. Enamel blocks were subjected to 9 days of pH-cycling in the presence of 1,000 ppm NaF (positive control), distilled-deionized water (DDW; negative control), 25 MUM 8DSS alone, 25 MUM 8DSS with 500 ppm NaF (8DSS-FL) or 25 MUM 8DSS with 1,000 ppm NaF (8DSS-FH) twice daily for 1 min each time. The blocks were analyzed in terms of surface microhardness (SMH), fluoride uptake and mineral content. The 8DSS-treated blocks showed significantly lower mineral loss, shallower lesions and higher SMH than the DDW-treated blocks. No significant differences were observed between the blocks treated with 8DSS alone or fluoride alone. The blocks treated with 8DSS alone or DDW showed similar amounts of fluoride uptake, which was the lowest of all the treatment groups. The blocks treated with 8DSS-FL or 8DSS-FH did not differ significantly, and both groups showed significantly greater SMH and fluoride uptake as well as significantly lower mineral loss and shallower lesions than the NaF-treated blocks. Mineral content was significantly higher in the 8DSS treated blocks than in the DDW-treated blocks from the surface layer (10 um) to the lesion depth (110 um), and it was significantly higher in the blocks treated with 8DSS-FL or 8DSS-FH than in the NaF-treated blocks from 10 to 90 um. These findings illustrate the potential of 8DSS for inhibiting enamel demineralization and for enhancing the anticaries effect of NaF. PMID- 26836440 TI - Thermoelectric Polymers and their Elastic Aerogels. AB - Electronically conducting polymers constitute an emerging class of materials for novel electronics, such as printed electronics and flexible electronics. Their properties have been further diversified to introduce elasticity, which has opened new possibility for "stretchable" electronics. Recent discoveries demonstrate that conducting polymers have thermoelectric properties with a low thermal conductivity, as well as tunable Seebeck coefficients - which is achieved by modulating their electrical conductivity via simple redox reactions. Using these thermoelectric properties, all-organic flexible thermoelectric devices, such as temperature sensors, heat flux sensors, and thermoelectric generators, are being developed. In this article we discuss the combination of the two emerging fields: stretchable electronics and polymer thermoelectrics. The combination of elastic and thermoelectric properties seems to be unique for conducting polymers, and difficult to achieve with inorganic thermoelectric materials. We introduce the basic concepts, and state of the art knowledge, about the thermoelectric properties of conducting polymers, and illustrate the use of elastic thermoelectric conducting polymer aerogels that could be employed as temperature and pressure sensors in an electronic-skin. PMID- 26836443 TI - The Role of Layer-Controlled Graphene for Tunable Microwave Heating and Its Applications to the Synthesis of Inorganic Thin Films. AB - In this paper, we present the first method for precisely controlling the heat generated by microwave heating by tuning the number of graphene layers grown by chemical vapor deposition. The conductivity of the graphene increases linearly with the number of graphene layers, indicating that Joule heating plays a primary role in the temperature control of the graphene layer. In this method, we successfully synthesize TiO2 and MoS2 thin films, which do not interact well with microwaves, on a layer-controlled graphene substrate for a very short time (3 min) through microwave heating. PMID- 26836442 TI - Inhibition by all-trans retinoic acid of collagen degradation mediated by corneal fibroblasts. AB - BACKGROUND: We examined the effect of all-trans retinoic acid on collagen degradation mediated by corneal fibroblasts. METHODS: Rabbit corneal fibroblasts were cultured with or without all-trans retinoic acid in a three-dimensional collagen gel, and the extent of collagen degradation was determined by measurement of hydroxyproline in acid hydrolysates of culture supernatants. Matrix metalloproteinase expression was examined by immunoblot analysis and gelatin zymography. The abundance and phosphorylation state of the endogenous nuclear factor-kappaB inhibitor IkappaB-alpha were examined by immunoblot analysis. Corneal ulceration was induced by injection of lipopolysaccharide into the central corneal stroma of rabbits and was assessed by observation with a slitlamp microscope. RESULTS: All-trans retinoic acid inhibited interleukin-1beta induced collagen degradation by corneal fibroblasts in a concentration- and time dependent manner. It also attenuated the release and activation of matrix metalloproteinases as well as the phosphorylation and degradation of IkappaB alpha induced by interleukin-1beta in these cells. Topical application of all trans retinoic acid suppressed corneal ulceration induced by injection of lipopolysaccharide into the corneal stroma. CONCLUSIONS: All-trans retinoic acid inhibited collagen degradation mediated by corneal fibroblasts exposed to interleukin-1beta, with this effect being accompanied by suppression of nuclear factor-kappaB signalling as well as of matrix metalloproteinase release and activation in these cells. All-trans retinoic acid also attenuated lipopolysaccharide-induced corneal ulceration in vivo. Our results therefore suggest that all-trans retinoic acid might prove effective for the treatment of patients with corneal ulceration. PMID- 26836444 TI - Study of the mechanical stability and bioactivity of Bioglass((r)) based glass ceramic scaffolds produced via powder metallurgy-inspired technology. AB - Large bone defects are challenging to heal, and often require an osteoconductive and stable support to help the repair of damaged tissue. Bioglass-based scaffolds are particularly promising for this purpose due to their ability to stimulate bone regeneration. However, processing technologies adopted so far do not allow for the synthesis of scaffolds with suitable mechanical properties. Also, conventional sintering processes result in glass de-vitrification, which generates concerns about bioactivity. In this work, we studied the bioactivity and the mechanical properties of Bioglass((r)) based scaffolds, produced via a powder technology inspired process. The scaffolds showed compressive strengths in the range of 5-40 MPa, i.e. in the upper range of values reported so far for these materials, had tunable porosity, in the range between 55 and 77%, and pore sizes that are optimal for bone tissue regeneration (100-500 MUm). We immersed the scaffolds in simulated body fluid (SBF) for 28 d and analyzed the evolution of the scaffold mechanical properties and microstructure. Even if, after sintering, partial de-vitrification occurred, immersion in SBF caused ion release and the formation of a Ca-P coating within 2 d, which reached a thickness of 10 15 MUm after 28 d. This coating contained both hydroxyapatite and an amorphous background, indicating microstructural amorphization of the base material. Scaffolds retained a good compressive strength and structural integrity also after 28 d of immersion (6 MPa compressive strength). The decrease in mechanical properties was mainly related to the increase in porosity, caused by its dissolution, rather than to the amorphization process and the formation of a Ca-P coating. These results suggest that Bioglass((r)) based scaffolds produced via powder metallurgy-inspired technique are excellent candidates for bone regeneration applications. PMID- 26836445 TI - Integrating Local, National, and International Stakeholders in Outbreak Preparedness in Developing Countries: Conclusions from a Conference in Mbeya, Tanzania. AB - A conference called "Outbreaks in Tanzania-Are We Prepared?" was held in Mbeya, Tanzania, on September 14 and 15, 2015, accompanied by a training workshop on infection prevention and control for local stakeholders from September 16 to 18, 2015. The objective of the conference was to revisit past disease epidemics and to reflect on the current status of surveillance and outbreak preparedness in Tanzania, including an overview of agents relevant to biosecurity. The conference brought together national authorities of Tanzania, regional public health representatives, people from research and academic institutions, and international stakeholders. Key findings of the event were: (1) although national frameworks for surveillance and preparedness exist, their implementation presents challenges, and local health structures need support in implementation; (2) the ability to identify and properly manage infectious diseases of public health concern is crucial in empowering the local health workforce to contribute to surveillance measures, which in turn allows for realistic risk assessments and management algorithms; and (3) in settings of limited resources, research activities acquire an additional responsibility toward national surveillance and capacity building and should be integrated into national epidemic preparedness plans. This event was the first of its kind in Tanzania, facilitating direct discussion among regional, zonal, national, and international stakeholders on surveillance and outbreak preparedness. The conference's conclusions are relevant to strengthening health systems in other low- and middle-income countries. PMID- 26836441 TI - A genomic perspective on hybridization and speciation. AB - Hybridization among diverging lineages is common in nature. Genomic data provide a special opportunity to characterize the history of hybridization and the genetic basis of speciation. We review existing methods and empirical studies to identify recent advances in the genomics of hybridization, as well as issues that need to be addressed. Notable progress has been made in the development of methods for detecting hybridization and inferring individual ancestries. However, few approaches reconstruct the magnitude and timing of gene flow, estimate the fitness of hybrids or incorporate knowledge of recombination rate. Empirical studies indicate that the genomic consequences of hybridization are complex, including a highly heterogeneous landscape of differentiation. Inferred characteristics of hybridization differ substantially among species groups. Loci showing unusual patterns - which may contribute to reproductive barriers - are usually scattered throughout the genome, with potential enrichment in sex chromosomes and regions of reduced recombination. We caution against the growing trend of interpreting genomic variation in summary statistics across genomes as evidence of differential gene flow. We argue that converting genomic patterns into useful inferences about hybridization will ultimately require models and methods that directly incorporate key ingredients of speciation, including the dynamic nature of gene flow, selection acting in hybrid populations and recombination rate variation. PMID- 26836447 TI - Wavelength Dependence of UV Photoemission from Solvated Electrons in Bulk Water, Methanol, and Ethanol. AB - We have measured the wavelength dependence (340-215 nm) of one-photon photoemission from the ground electronic state of solvated electrons in bulk water, methanol, and ethanol. In every case, the vertical electron binding energy (VBE) gradually increased with photon energy, indicating that the photoelectron kinetic energy diminishes as a result of electron-vibration inelastic scattering prior to emission from the liquid surface. In contrast, the VBE of the Rydberg electron in DABCO (1,4-diazabicyclo[2,2,2]octane), which has a surface-excess density, revealed no clear wavelength dependence. These results suggest that the solvated electrons are created predominantly in the bulk and that VBEs measured using UV photoemission spectroscopy of liquids generally require energy corrections to account for inelastic scattering effects. From the wavelength dependence, we have re-estimated the VBEs of solvated electrons in bulk water, methanol, and ethanol to be 3.3, 3.1, and 3.1 eV, respectively. Hydrated electrons were also identified by photoemission spectroscopy using 90 nm radiation. PMID- 26836446 TI - Characterization of an IgG monoclonal antibody targeted to both tissue cyst and sporocyst walls of Toxoplasma gondii. AB - Toxoplasma gondii infects animals habiting terrestrial and aquatic environments. Its oocysts and tissue cysts are important for the horizontal transmission of this parasite. The oocyst and tissue cyst walls are crucial for the ability of the parasite to persist in the environment or in animal tissues, respectively. However, the composition of these walls is not well understood. We report the generation of monoclonal antibodies directed against wall components using mice immunized with oocyst antigens of T. gondii. One monoclonal antibody (mAb) G1/19 reacted solely with T. gondii sporozoites. The respective antigen had a relative molecular weight (Mr) of 30 kDa. MAb G1/19 failed to react with sporozoites of any other coccidian parasite species tested (Hammondia hammondi, Hammondia heydorni, Cystoisospora felis, Eimeria bovis, Sarcocystis sp.). Another mAb, designated K8/15-15, recognized antigens in sporocyst walls of the parasite and in the walls of in vivo or in vitro produced tissue cysts, as demonstrated by immunofluorescence and immunoblot assays. Antigens of 80 to a high molecular weight protein of about 350 kDa Mr were recognized by this antibody using antigen extracts from sporocysts, and from in vitro or in vivo generated tissue cysts of the parasite. Tissue cyst and sporocyst walls of H. hammondi and H. heydorni, and tissue cysts of Neospora caninum were also recognized by mAb K8/15-15. Sporocyst walls of C. felis also reacted to this mAb. The cyst walls of Sarcocystis sp. and Besnoitia besnoiti were not recognized by mAb K8/15-15. Reactivity by a single mAb against T. gondii antigens in tissue cysts and sporocysts had not been reported previously. MAb K8/15-15 may be a practical tool for the identification of both cysts and sporocysts of the parasite, and may also be potentially employed in proteomic studies on the identification of new components of the cyst and sporocyst walls of T. gondii. PMID- 26836449 TI - Comparative study between recent methods manipulating ratio spectra and classical methods based on two-wavelength selection for the determination of binary mixture of antazoline hydrochloride and tetryzoline hydrochloride. AB - A comparative study was developed between two classical spectrophotometric methods (dual wavelength method and Vierordt's method) and two recent methods manipulating ratio spectra (ratio difference method and first derivative of ratio spectra method) for simultaneous determination of Antazoline hydrochloride (AN) and Tetryzoline hydrochloride (TZ) in their combined pharmaceutical formulation and in the presence of benzalkonium chloride as a preservative without preliminary separation. The dual wavelength method depends on choosing two wavelengths for each drug in a way so that the difference in absorbance at those two wavelengths is zero for the other drug. While Vierordt's method, is based upon measuring the absorbance and the absorptivity values of the two drugs at their lambda(max) (248.0 and 219.0 nm for AN and TZ, respectively), followed by substitution in the corresponding Vierordt's equation. Recent methods manipulating ratio spectra depend on either measuring the difference in amplitudes of ratio spectra between 255.5 and 269.5 nm for AN and 220.0 and 273.0 nm for TZ in case of ratio difference method or computing first derivative of the ratio spectra for each drug then measuring the peak amplitude at 250.0 nm for AN and at 224.0 nm for TZ in case of first derivative of ratio spectrophotometry. The specificity of the developed methods was investigated by analyzing different laboratory prepared mixtures of the two drugs. All methods were applied successfully for the determination of the selected drugs in their combined dosage form proving that the classical spectrophotometric methods can still be used successfully in analysis of binary mixture using minimal data manipulation rather than recent methods which require relatively more steps. Furthermore, validation of the proposed methods was performed according to ICH guidelines; accuracy, precision and repeatability are found to be within the acceptable limits. Statistical studies showed that the methods can be competitively applied in quality control laboratories. PMID- 26836450 TI - Reusable fluorescent photocrosslinked polymeric sensor for determining lead ions in aqueous media. AB - In this study, 1-vinylimidazole units bearing photocured films were prepared as fluorescent sensors towards Pb(2+) in aqueous solutions. The influence of experimental parameters such as pH, time and foreign ion concentrations were investigated. Sensor response was linear over a concentration range of 4.83*10( 8) to 4.83*10(-7) mol L(-1). The sensor was highly sensitive with a detection limit as low as 1.87*10(-8)molL(-1), and having a selectivity of over four thousand fold. The response time of the sensor was found to be 5 min. When stored in a desiccator at room temperature the sensor showed good stability after a 5 month period. The fluorescence sensors were successful in the determination of Pb(2+) in water samples as well as in the determination of the quantitative amount of lead and the results were satisfying. Compared with previously reported literature, the prepared new sensor is highly sensitive and selective. PMID- 26836451 TI - Interactions of D-cellobiose with selected chloride salts: A 13C NMR and FT-IR study. AB - The interactions of cellulose model compound d-cellobiose with chloride salts of Zn(2+), Ca(2+), Li(+), Sn(2+), La(3+), Mg(2+), K(+) and NH4(+) were evaluated by measuring the (13)C NMR chemical shift changes (Deltadelta) of the disaccharide due to the addition of salts in D2O. The KCl and NH4Cl showed similar Deltadelta changes due to interactions only with the Cl(-) anion. Whereas other chloride salts showed interactions with both cation and anion. Among these salts the total interactions are in the order: Zn(2+)>Sn(2+)>Li(+)>Ca(2+)~La(3+)>Mg(2+). The FT IR spectra of D-cellobiose-chloride salt 1:2 mixtures also indicate that KCl and NH4Cl interacts similarly with D-cellobiose in the solid state. PMID- 26836448 TI - Synthetic Strategies toward Natural Products Containing Contiguous Stereogenic Quaternary Carbon Atoms. AB - Strategies for the total synthesis of complex natural products that contain two or more contiguous stereogenic quaternary carbon atoms in their intricate structures are reviewed with 12 representative examples. Emphasis has been put on methods to create quaternary carbon stereocenters, including syntheses of the same natural product by different groups, thereby showcasing the diversity of thought and individual creativity. A compendium of selected natural products containing two or more contiguous stereogenic quaternary carbon atoms and key reactions in their total or partial syntheses is provided in the Supporting Information. PMID- 26836452 TI - Investigation on the hazing of a Brazilian contemporary painting. AB - A whitish crystalline-like coating was observed on the surface of the painting "Incendio", 1990, produced by Emmanuel Nassar and awarded at the 6th Biennial of Cuenca. This work belongs to the Contemporary Art Museum of the University of Sao Paulo (MAC-USP) and such coating modified the artwork characteristics, causing an unpleasant effect and compromising its exhibition. The choice of the proper conservation and restoration strategies involves the understanding of the degradation process, demanding the identification of the chemical compounds formed on the painting surface, as well as of the other components in the painting. The results here obtained from Raman and optical microscopies, FTIR ATR, SEM-EDS and GC-MS, revealed that the efflorescence chemical composition is almost only palmitic acid, with minor contents of stearic acid and their methyl esters, and that the paints are composed by chrome yellow, amorphous carbon and toluidine red pigment; an aluminum silicate filler in the black paint applied on the aluminum ground was also detected. Hierarchical Cluster Analyses (HCA) of the Raman spectra also revealed that the concentration of the efflorescence minor components depends on the paint composition. It was suggested, therefore, that the degradation process resulted from segregation and migration of mainly palmitic acid from the dried paints. Restoration methodologies used in similar cases, as well as factors that contribute to this process, were discussed. PMID- 26836453 TI - The fast method of Cu-porphyrin complex synthesis for potential use in positron emission tomography imaging. AB - Porphyrin based photosensitizers are useful agents for photodynamic therapy and fluorescence imaging of cancer. Additionally, porphyrins are excellent metal chelators, forming stable metalo-complexes and (64)Cu isotope can serve as a positron emitter (t1/2=12.7h). The other advantage of (64)Cu is its decay characteristics that facilitates the use of (64)Cu-porphyrin complex as a therapeutic agent. Thus, (64)Cu chelation with porphyrin photosensitizer may become a simple and versatile labeling strategy for clinical positron emission tomography. The present study reports a convenient method for the synthesis of Cu complex with tetrakis(4-carboxyphenyl)porphyrin (TCPP). The experimental conditions for labeling, such as the metal-to-ligand molar ratio, pH and time of reaction were optimized to achieve a high complexation efficiency in a short period of time as possible. In order to accelerate the metallation, the use of substitution reactions of cadmium or lead porphyrin and the presence of reducing agent, such as ascorbic acid, hydroxylamine and flavonoid - morin, were evaluated. The optimum conditions for the synthesis of the copper complex were borate buffer at pH9 with the addition of 10-fold molar excess, with respect to Cu(2+) ions and TCPP and ascorbic acid which resulted in reduction of the reaction time from 30 min to below 1 min. PMID- 26836454 TI - Spectroscopic studies on the inhibitory effects of ionic liquids on lipase activity. AB - The effects of ionic liquids (ILs) on the lipase activity were studied by UV-Vis spectroscopy and the IL-lipase interaction mechanism at the molecular level was investigated by fluorescence technique. Experimental results indicated that the lipase activity was inhibited by ILs and the degree of inhibition highly depended on the chemical structures of ILs. The inhibitory ability of the Cl(-)- and Br(-) based ILs increased with increasing the alkyl chain length in the IL cation. Thermodynamic parameters, enthalpy change (DeltaH) and entropy change (DeltaS) were obtained by analyzing the fluorescence behavior of lipase with the addition of ILs. Both DeltaH and DeltaS were positive suggesting hydrophobicity was the major driven force for the Cl(-)- and Br(-)-based ILs. For the BF4(-)-, CF3SO3(-) , ClO4(-)- and N(CN)2(-)-based ILs, hydrogen bonding was the main driven force. For a more comprehensive understanding of the effects of ILs on lipase activity, the roles of hydrophobicity and hydrogen bonding must be considered simultaneously. A regression-based equation was developed to describe the relationship of the inhibitory ability of ILs and their hydrophobicity and hydrogen bonding ability. PMID- 26836455 TI - Detection and aggregation of the antitumoral drug parietin in ethanol/water mixture and on plasmonic metal nanoparticles studied by surface-enhanced optical spectroscopy: Effect of pH and ethanol concentration. AB - In the present paper, we have investigated the effect of ethanol in aqueous media, the pH and the presence of Ag nanoparticles (NPs) on the aggregation processes of the antitumoral anthraquinone parietin in aqueous media and on the metal surface. UV-visible absorption, fluorescence and Raman spectra of parietin were used for such purpose. The present study provides information about the deprotonation and molecular aggregation processes occurring in parietin under different environments: ethanol/water mixture and when adsorbed onto Ag nanoparticles. The effect of ethanol on the optical properties of parietin in alcohol-water mixtures was also investigated at different ethanol concentrations with the time. For the case of the adsorption and organization of parietin molecules on the surface of Ag NPs, special attention was paid to the use of surface-enhanced optical techniques, SEF (surface-enhanced fluorescence) and SERS (surface-enhanced Raman scattering), for the characterization of the parietin aggregates and the ionization of the molecule on the surface. In particular, we have studied the variation of the SEF signal with the pH, which depends on the molecular organization of the molecule on the surface. Furthermore, a detailed analysis of the SERS spectra at different pH was accomplished and the main Raman bands of the protonated, mono-deprotonated and di-deprotonated parietin were identified. Finally, the second ionization pK of parietin on metal NPs was deduced from the SERS spectra. PMID- 26836456 TI - Recognition of steric factor in external association of xanthenocrown-5 and bis napthalenocrown-6 with bis(benzimidazolium)propane borontetrafluoride. AB - This is the first report of charge transfer band for crown-axel H-bonding interaction in acetonitrile medium. Monte Carlo simulation established external association of small cavity crown with BBIM-propane dication axels. Resonance energy, binding constant and ratiometric detection of association of xanthenocrown-5 (1) and bis-napthalenocrown-6 (2) with bis (benzimidazolium)propane borontetrafluoride (3a-3d) in acetonitrile determined the effect of steric factor towards association. PMID- 26836457 TI - The Last Possible Outposts for Life on Mars. AB - The evolution of habitable conditions on Mars is often tied to the existence of aquatic habitats and largely constrained to the first billion years of the planet. Here, we propose an alternate, lasting evolutionary trajectory that assumes the colonization of land habitats before the end of the Hesperian period (ca. 3 billion years ago) at a pace similar to life on Earth. Based on the ecological adaptations to increasing dryness observed in dryland ecosystems on Earth, we reconstruct the most likely sequence of events leading to a late extinction of land communities on Mars. We propose a trend of ecological change with increasing dryness from widespread edaphic communities to localized lithic communities and finally to communities exclusively found in hygroscopic substrates, reflecting the need for organisms to maximize access to atmospheric sources of water. If our thought process is correct, it implies the possibility of life on Mars until relatively recent times, perhaps even the present. PMID- 26836458 TI - The association between reduced aspirin responsiveness as assessed by impedance aggregometry and adverse outcomes after cardiac surgery: methodological considerations. PMID- 26836459 TI - Defects and disorder in metal organic frameworks. AB - The wide-ranging properties of metal organic frameworks (MOFs) rely in many cases on the presence of defects within their structures and the disorder that is inevitably associated with such defects. In the present work we review several aspects of defects in MOFs, ranging from simple substitutional defects at metal cation or ligand positions, to correlated defects on a larger length scale and the extreme case of disorder associated with amorphous MOFs. We consider both porous and dense MOFs, and focus particularly on the way in which defects and disorder can be used to tune physical properties such as gas adsorption, catalysis, photoluminescence, and electronic and mechanical properties. PMID- 26836460 TI - Glycyrrhizic acid prevents ultraviolet-B-induced photodamage: a role for mitogen activated protein kinases, nuclear factor kappa B and mitochondrial apoptotic pathway. AB - Glycyrrhizic acid (GA), a natural triterpene, has received attention as an agent that has protective effects against chronic diseases including ultraviolet UV-B induced skin photodamage. However, the mechanism of its protective effect remains elusive. Here, we used an immortalized human keratinocyte cell line (HaCaT) and a small animal model (BALB/c mice), to investigate the protective effects of GA against UV-B-induced oxidative damage, and additionally, delineated the molecular mechanisms involved in the UV-B-mediated inflammatory and apoptotic response. In the HaCaT cells, GA inhibited the UV-B-mediated increase in intracellular reactive oxygen species (ROS) and down-regulated the release of pro-inflammatory cytokines interleukin (IL)-1alpha, -1beta and -6, tumor necrosis factor (TNF) alpha and prostaglandin E2 (PGE2). GA inhibited UV-B-mediated activation of p38 and JNK MAP kinases, COX-2 expression and nuclear translocation of NF-kappaB. Furthermore, GA inhibited UV-B-mediated apoptosis by attenuating translocation of Bax from the cytosol to mitochondria, thus preserving mitochondrial integrity. GA treated HaCaT cells also exhibited elevated antiapoptotic Bcl-2 protein, concomitant with reduced caspase-3 cleavage and decreased PARP-1 protein. In BALB/c mice, topical application of GA on dorsal skin exposed to UV-B irradiation protected against epidermal hyperplasia, lymphocyte infiltration and expression of several inflammatory proteins, p38, JNK, COX-2, NF-kappaB and ICAM-1. Based on the above findings, we conclude that GA protects against UV-B-mediated photodamage by inhibiting the signalling cascades triggered by oxidative stress, including MAPK/NF-kappaB activation, as well as apoptosis. Thus, GA has strong potential to be used as a therapeutic/cosmeceutical agent against photodamage. PMID- 26836461 TI - Evidence of a subcommissural organ involvement in the brain response to lead exposure and a modulatory potential of curcumin. AB - Substantial evidence supports the neurochemical vulnerability to lead (Pb) as one of the most potent neurotoxic heavy metals. In the present study, we aimed to assess: (i) The subcommissural organ (SCO) responsiveness as a secretory circumventricular organ to chronic and acute Pb intoxication together with its serotoninergic innervation. (ii) The possible restorative effect of curcumin against Pb intoxication under the same pathological conditions. We used immunohistochemistry with antibodies against Reissner's fiber and serotonin [5 hydroxytryptophan (5-HT)] in Wistar rats following chronic as well as acute Pb administration, respectively, at 25 mg/kg intraperitoneally for 3 days and 0.3% in drinking water from the intrauterine stage until 2 months of adult age. Our data showed a significant decrease in Reissner's fiber material immunoreactivity concomitant with an overall increased 5-HT innervation of the SCO and the ventricular borders. Coadministration of curcumin (50 mg/kg body weight) restores this impairment by reversing the effect of chronic and acute Pb on the secretory activity and the 5-HTergic innervation of the SCO. The investigation showed, on the one hand, the involvement of the SCO in the response to heavy metals, especially Pb, and on the other, the beneficial corrector role of curcumin. As a part of the circumventricular organ, known as a privileged area of brain-blood exchanges, the SCO may play a key role in the mechanism of brain defense against heavy metal neurotoxicity in rats. PMID- 26836462 TI - Association of occlusal interference-induced masseter muscle hyperalgesia and P2X3 receptors in the trigeminal subnucleus caudalis and midbrain periaqueductal gray. AB - P2X3 receptor plays a role in nociception transmission of orofacial pain in temporomandibular disorder patients. A previous study found that P2X3 receptors in masseter muscle afferent neurons and the trigeminal ganglia were involved in masseter muscle pain induced by inflammation caused by chemical agents or eccentric muscle contraction. In this study, we attempted to investigate changes in P2X3 receptors in the trigeminal subnucleus caudalis (Vc) and midbrain periaqueductal gray (PAG) in relation to the hyperalgesia of masseter muscles induced by occlusal interference. Experimental occlusal interference by crown application was established in 30 rats and another 30 rats were treated as sham controls. On days 1, 3, 7, 14, and 28 after crown application, the mechanical pain threshold was examined by von-Frey filaments. The expression of the P2X3 receptor in Vc and PAG was investigated by immunohistochemistry and quantitative PCR. We found that mechanical pain threshold of bilateral masseter muscles decreased significantly after occlusal interference, which remained for the entire experimental period. The mRNA expression of the P2X3 receptor increased significantly and the number of P2X3R-positive neurons increased markedly in Vc and PAG accordingly. These results indicate that the upregulated expression of P2X3 receptors in Vc and PAG may contribute toward the development of orofacial pain induced by occlusal interference and P2X3 receptors in the PAG may play a key role in the supraspinal antiociception effect. PMID- 26836463 TI - Serum uric acid levels in patients with myasthenia gravis are inversely correlated with disability. AB - Uric acid (UA), the final product of purine metabolism, has been reported to be reduced in patients with various neurological disorders and is considered to be a possible indicator for monitoring the disability and progression of multiple sclerosis. However, it remains unclear whether there is a close relationship between UA and myasthenia gravis (MG), or whether UA is primarily deficient or secondarily reduced because of its peroxynitrite scavenging activity. We investigated the correlation between serum UA levels and the clinical characteristics of MG. We assessed 338 serum UA levels obtained in 135 patients with MG, 47 patients with multiple sclerosis, and 156 healthy controls. In addition, we compared serum UA levels when MG patients were stratified according to disease activity and classifications performed by the Myasthenia Gravis Foundation of America, age of onset, duration, and thymus histology (by means of MRI or computed tomography). MG patients had significantly lower serum UA levels than the controls (P<0.001). Moreover, UA levels in patients with MG were inversely correlated with disease activity and disease progression (P=0.013). However, UA levels did not correlate significantly with disease duration, age of onset, and thymus histology. Our findings suggest that serum level of UA was reduced in patients with MG and serum UA might be considered a surrogate biomarker of MG disability and progression. PMID- 26836464 TI - Evaluating the Impact of Classroom Education on the Management of Septic Shock Using Human Patient Simulation. AB - BACKGROUND: Classroom lectures are the mainstay of imparting knowledge in a structured manner and have the additional goals of stimulating critical thinking, lifelong learning, and improvements in patient care. The impact of lectures on patient care is difficult to examine in critical care because of the heterogeneity in patient conditions and personnel as well as confounders such as time pressure, interruptions, fatigue, and nonstandardized observation methods. METHODS: The critical care environment was recreated in a simulation laboratory using a high-fidelity mannequin simulator, where a mannequin simulator with a standardized script for septic shock was presented to trainees. The reproducibility of this patient and associated conditions allowed the evaluation of "clinical performance" in the management of septic shock. In a previous study, we developed and validated tools for the quantitative analysis of house staff managing septic shock simulations. In the present analysis, we examined whether measures of clinical performance were improved in those cases where a lecture on the management of shock preceded a simulated exercise on the management of septic shock. The administration of the septic shock simulations allowed for performance measurements to be calculated for both medical interns and for subsequent management by a larger resident-led team. RESULTS: The analysis revealed that receiving a lecture on shock before managing a simulated patient with septic shock did not produce scores higher than for those who did not receive the previous lecture. This result was similar for both interns managing the patient and for subsequent management by a resident-led team. CONCLUSIONS: We failed to find an immediate impact on clinical performance in simulations of septic shock after a lecture on the management of this syndrome. Lectures are likely not a reliable sole method for improving clinical performance in the management of complex disease processes. PMID- 26836465 TI - Simulation Study Assessing Healthcare Provider's Knowledge of Pre-Eclampsia and Eclampsia in a Tertiary Referral Center. AB - INTRODUCTION: The aim of the study was to assess knowledge of labor and delivery healthcare providers at a tertiary referral center in the management of pre eclampsia and eclampsia. METHODS: Thirteen multidisciplinary teams participated in this institutional review board-exempt study. Each group encountered the same scenario that involved a pre-eclamptic parturient who progressed to eclampsia. The participants were unaware of the scenario topic before the drill and that key interventions would be recorded and timed. Seven of 13 groups were randomized to have a cognitive aid available. RESULTS: Twelve of 13 groups attempted to lower the blood pressure; however, only 7 of 12 groups used the correct first-line antihypertensive medication as per the American College of Obstetricians and Gynecologists' guidelines. All groups requested and administered the correct bolus dose of magnesium (4-6 g intravenously). Only 2 of 13 groups took appropriate action to lower the blood pressure to a "safe range" before induction of general anesthesia, and 4 of the 13 anesthesiologists made drug modifications for induction of anesthesia. None of the 7 groups randomized to have a cognitive aid used it. CONCLUSIONS: Our results show widespread magnesium sulfate utilization; however, the use of antihypertensive medication is not universally administered in compliance with current guidelines. The importance of blood pressure management to reduce maternal morbidity and mortality in the setting of pre-eclampsia needs to be emphasized. Interestingly, availability of a cognitive aid did not ensure its utilization in this scenario. Findings suggest that for cognitive aids to be effectively used, it is essential that staff has been trained and become familiar with them before an emergent event. PMID- 26836466 TI - Learner-Centered Debriefing for Health Care Simulation Education: Lessons for Faculty Development. AB - STATEMENT: Better debriefing practices may enhance the impact of simulation-based education. Emerging literature suggests that learner-centered debriefing may be effective in helping instructors identify and address learner needs while building learner's engagement and sense of responsibility for learning. This contrasts with instructor-centered approaches to debriefing, where instructors maintain unilateral control over both the process and content of the debriefing, thus limiting input and direction from learners. Although different approaches to debriefing for simulation-based education exist, the simulation literature is largely mute on the topic of learner-centered debriefing. In this article we will (1) compare and contrast learner- versus instructor-centered approaches to teaching; (2) provide a rationale for applying more learner-centered approaches to debriefing; (3) introduce a conceptual framework that highlights the key dimensions of learner- versus instructor-centered debriefing; (4) describe key variables to consider when managing the balance between learner- and instructor centered debriefing; and (5) describe practical learner-centered strategies for various phases of debriefing. PMID- 26836467 TI - A Novel Mammoplasty Part-Task Trainer for Simulation of Breast Augmentation: Description and Evaluation. AB - INTRODUCTION: Since the introduction of competency-based education and the restriction of residents' working hours, simulator-aided training has obtained increasing attention for its role in teaching and assessing resident surgical skills. Within plastic surgery training, such simulators would be particularly useful for aesthetic surgery procedures such as augmentation mammoplasty where residents have fewer opportunities for hands-on experience. The aims of this study were to develop a part-task trainer that allows plastic surgery trainees to acquire skills necessary for augmentation mammoplasty and to assess its potential value as a training tool. METHODS: The mammoplasty part-task trainer (MPT) was designed to have a reusable and rigid thorax base and "soft" disposable layers to mimic the skin and subcutaneous tissues. A mock unilateral subglandular breast augmentation was performed by 4 board-certified plastic surgeons using standard instruments and scored using a 0 to 5 Likert scale where a score of 5 was considered the most satisfactory. RESULTS: Four board-certified plastic surgeons participated in the survey. On a scale of 0 to 5, the MPT's "value" as a training tool, "relevance to practice," and "physical attributes" scored highest, with mean values of 4.5, 4.3, and 4.1, respectively. "Realism of experience," "ability to perform tasks," and "realism of material" scored 3.9, 3.8, and 3.7, respectively. The observed average of the "global assessment" of the MPT was 4.3. The cost of fabrication of the MPT was estimated at approximately Can $113. CONCLUSIONS: This study describes a preliminary novel mammoplasty task trainer that was highly valued by experts as a potential training tool. PMID- 26836468 TI - Use of Simulation to Validate Questionnaires on a Sensitive Subject. PMID- 26836469 TI - The Application of Cognitive Load Theory to Dual-Task Simulation Training. PMID- 26836471 TI - Early indoor aeroallergen exposure is not associated with development of sensitization or allergic rhinitis in high-risk children. AB - RATIONALE: Allergen exposure is associated with the development of allergic sensitization in childhood as reflected by global variations in sensitization patterns. However, there is little evidence to support a direct association. OBJECTIVES: To investigate the association between perinatal aeroallergen exposure and sensitization and rhinitis to such allergens later in childhood. METHODS: Allergic sensitization to cat, dog, and house dust mites was diagnosed longitudinally using skin prick tests and specific IgE measurements at 1/2, 11/2, 4, 6, and 13 years in 399 children from the Copenhagen Prospective Study on Asthma in Childhood2000 birth cohort. Rhinitis was diagnosed at 7 and 13 years. Allergen exposure was defined as dog or cat in the home during the 3rd trimester of pregnancy or the first year of life and as allergen levels of dog, cat, and house dust mite in bed dust samples at 1 year. Associations between exposure and outcomes were analyzed by logistic regression and stratified for eczema status and test method (skin prick test and specific IgE). RESULTS: We found no association between dog or cat exposure in perinatal life and sensitization or rhinitis during childhood. Similarly, there was no association between levels of allergens in bed dust samples and sensitization or rhinitis during childhood. CONCLUSION: Perinatal indoor aeroallergen exposure does not seem to affect development of allergic sensitization or rhinitis during childhood questioning the relevance of allergen avoidance as a preventive measure. Other factors such as timing of allergen exposure or other environmental adjuvants may contribute in a more complex pathway to sensitization. PMID- 26836472 TI - Evolution of the Cannabinoid and Terpene Content during the Growth of Cannabis sativa Plants from Different Chemotypes. AB - The evolution of major cannabinoids and terpenes during the growth of Cannabis sativa plants was studied. In this work, seven different plants were selected: three each from chemotypes I and III and one from chemotype II. Fifty clones of each mother plant were grown indoors under controlled conditions. Every week, three plants from each variety were cut and dried, and the leaves and flowers were analyzed separately. Eight major cannabinoids were analyzed via HPLC-DAD, and 28 terpenes were quantified using GC-FID and verified via GC-MS. The chemotypes of the plants, as defined by the tetrahydrocannabinolic acid/cannabidiolic acid (THCA/CBDA) ratio, were clear from the beginning and stable during growth. The concentrations of the major cannabinoids and terpenes were determined, and different patterns were found among the chemotypes. In particular, the plants from chemotypes II and III needed more time to reach peak production of THCA, CBDA, and monoterpenes. Differences in the cannabigerolic acid development among the different chemotypes and between monoterpene and sesquiterpene evolution patterns were also observed. Plants of different chemotypes were clearly differentiated by their terpene content, and characteristic terpenes of each chemotype were identified. PMID- 26836470 TI - Corticospinal excitability is associated with hypocapnia but not changes in cerebral blood flow. AB - KEY POINTS: Reductions in cerebral blood flow (CBF) may be implicated in the development of neuromuscular fatigue; however, the contribution from hypocapnic induced reductions (i.e. P ETC O2) in CBF versus reductions in CBF per se has yet to be isolated. We assessed neuromuscular function while using indomethacin to selectively reduce CBF without changes in P ETC O2 and controlled hyperventilation-induced hypocapnia to reduce both CBF and P ETC O2. Increased corticospinal excitability appears to be exclusive to reductions in P ETC O2 but not reductions in CBF, whereas sub-optimal voluntary output from the motor cortex is moderately associated with decreased CBF independent of changes in P ETC O2. These findings suggest that changes in CBF and P ETC O2 have distinct roles in modulating neuromuscular function. ABSTRACT: Although reductions in cerebral blood flow (CBF) may be involved in central fatigue, the contribution from hypocapnia-induced reductions in CBF versus reductions in CBF per se has not been isolated. This study examined whether reduced arterial PCO2 (P aC O2), independent of concomitant reductions in CBF, impairs neuromuscular function. Neuromuscular function, as indicated by motor-evoked potentials (MEPs), maximal M wave (Mmax ) and cortical voluntary activation (cVA) of the flexor carpi radialis muscle during isometric wrist flexion, was assessed in ten males (29 +/- 10 years) during three separate conditions: (1) cyclooxygenase inhibition using indomethacin (Indomethacin, 1.2 mg kg(-1) ) to selectively reduce CBF by 28.8 +/- 10.3% (estimated using transcranial Doppler ultrasound) without changes in end tidal PCO2 (P ETC O2); (2) controlled iso-oxic hyperventilation-induced reductions in P aC O2 (Hypocapnia), P ETC O2 = 30.1 +/- 4.5 mmHg with related reductions in CBF (21.7 +/- 6.3%); and (3) isocapnic hyperventilation (Isocapnia) to examine the potential direct influence of hyperventilation-mediated activation of respiratory control centres on CBF and changes in neuromuscular function. Change in MEP amplitude (%Mmax ) from baseline was greater in Hypocapnia tha in Isocapnia (11.7 +/- 9.8%, 95% confidence interval (CI) [2.6, 20.7], P = 0.01) and Indomethacin (13.3 +/- 11.3%, 95% CI [2.8, 23.7], P = 0.01) with a large Cohen's effect size (d >= 1.17). Although not statistically significant, cVA was reduced with a moderate effect size in Indomethacin (d = 0.7) and Hypocapnia (d = 0.9) compared to Isocapnia. In summary, increased corticospinal excitability - as reflected by larger MEP amplitude - appears to be exclusive to reduced P aC O2, but not reductions in CBF per se. Sub-optimal voluntary output from the motor cortex is moderately associated with decreased CBF, independent of reduced P aC O2. PMID- 26836474 TI - Organocatalytic Asymmetric Biginelli-like Reaction Involving Isatin. AB - The first asymmetric, Bronsted acid catalyzed Biginelli-like reaction of a ketone has been developed, employing N-substituted isatins as carbonyl substrates, and urea and alkyl acetoacetates as further components. BINOL-derived phosphoric acid catalysts have been used to achieve the synthesis of a small library of chiral, enantioenriched spiro(indoline-pyrimidine)-diones derivatives. The absolute configuration of the new spiro stereocenter was assessed on diastereoisomeric derivatives through computer-assisted NMR spectroscopy. X-ray diffractometry allowed the disclosure of the overall molecular conformation in the solid state and the characterization of the crystal packing of a Br-substituted Biginelli like derivative, while computational studies on the reaction transition state allowed us to rationalize the stereochemical outcome. PMID- 26836473 TI - The effect of ozonated sterile saline irrigation on the endometrium - A preliminary study. AB - The objective of this study was to evaluate the effect of sterile ozonated saline endometrial irrigation on sonographic and histological endometrial parameters. This prospective investigation was performed in 12 healthy, ovulating women over three consecutive menstrual cycles: control cycle (endometrial irrigation with 10 cc of normal saline at day 10), no intervention cycle and study cycle (irrigation with 10 cc of sterile ozonated saline at day 10). Endometrial thickness was measured by transvaginal ultrasound at days 10 and 12 of the control and study cycles, and endometrial samplings were obtained from the participants two days after the irrigations (i.e. on day 12) for histological evaluation. Ozonated saline irrigation, compared to normal saline irrigation, resulted in a statistically significant elevation of the columnar epithelial height (30.30 +/- 3.04 vs. 25.82 +/- 3.28 MUm, p < 0.003), increased number of endometrial blood vessels (30.48 +/- 11.38 vs. 19.12 +/- 8.74, p < 0.005) and increased number of stromal cells (191.30 +/- 34.40 vs. 151.29 +/- 29.98, p < 0.01). In conclusion, sterile ozonated saline irrigation of the endometrium has a significant favourable effect on various histological endometrial parameters. Further studies are needed to evaluate the effect of these changes on endometrial receptivity and pregnancy rates. PMID- 26836475 TI - Impaired CD98 signaling protects against graft-versus-host disease by increasing regulatory T cells. AB - Graft-versus-host disease (GvHD) is a major barrier to the broader use of allogenic hematopoietic stem cell transplantation for non-malignant clinical applications. A murine model of C57BL/6 to B6D2F1 acute GvHD was employed with T lymphocytes harboring a deletion of the CD98 heavy chain (CD98hc(-/-)) as donor cells. The CD98hc(-/-) resulted in lower responses to alloantigen stimulation in a mixed leukocyte reaction assay, and prevented the mortality associated with disease progression. The percentage of donor CD8 T lymphocytes was significantly decreased, while the percentage of Foxp3-positive regulatory T cells (Tregs) in recipients was increased by CD98hc(-/-). Decreased expression of FAS, FASL, ICOS, ICOSL, PD-1 and PD-L1 by donor CD8 T cells, and mRNA expression of cytotoxic T cell-related cytokines in the recipients were shown in those with CD98hc(-/-). Fewer infiltrated cells are found in the lungs, liver, tongue and skin of recipients with CD98hc(-/-) compared with the wild type recipients. Taken together, our data indicate that T cell-specific deletion of CD98hc can contribute to the prevention of GvHD development due to the attenuation of lymphocyte migration and by increasing the generation of Treg cells. These findings are expected to make it possible to develop novel approaches for the prevention of GvHD. PMID- 26836476 TI - Calcineurin and mTOR inhibitors have opposing effects on regulatory T cells while reducing regulatory B cell populations in kidney transplant recipients. AB - BACKGROUND: Regulatory B (Breg) and T (Treg) cells represent a biomarker for tolerance in transplant patients. Despite the importance of Treg and Breg in transplantation and the suggested crosstalk between both suppressive cell populations, little is known on how they are influenced by long-term immunosuppressive treatment. The aim of the present study was to investigate the effect of different immunosuppressive drugs used in routine clinical practice on Treg and Breg cell numbers. METHODS: Thirty-six kidney transplant recipients with stable graft function were recruited and classified according to their concomitant therapy: 22 patients received calcineurin inhibitors (CNI) and 14 patients received mammalian target of rapamycin (mTOR) inhibitors. A group of 8 healthy untreated subjects was included as control. Absolute numbers of peripheral blood-derived IL10-producing B cells (CD19(+)IL10(+)), CD19(+)CD24(hi)CD38(hi) transitional B cells and Treg cells (CD4(+)CD25(+)FOXP3(+)) were quantified in all KT patients and controls by flow cytometry. RESULTS: CD19(+)CD24(hi)CD38(hi) transitional B cells increased over time and seem to be related with long-term therapeutic graft survival irrespective of the treatment regimen. CNI and mTOR inhibitors significantly reduced numbers of Breg cells when compared with healthy individuals, whereas mTOR inhibitors expanded Treg cells in comparison with CNI drugs. CONCLUSIONS: Bridging the drug-mediated reduction of Breg cell numbers in vivo with the requirements of Breg cells for long-term transplant success remains an as yet unresolved task for therapeutic intervention. Further larger cohort studies that evaluate the effect of different treatment regimen on defined lymphocyte subpopulations are warranted. PMID- 26836477 TI - Reducing Compounds Equivocally Influence Oxidation during Digestion of a High-Fat Beef Product, which Promotes Cytotoxicity in Colorectal Carcinoma Cell Lines. AB - We studied the formation of malondialdehyde, 4-hydroxy-nonenal, and hexanal (lipid oxidation products, LOP) during in vitro digestion of a cooked low-fat and high-fat beef product in response to the addition of reducing compounds. We also investigated whether higher LOP in the digests resulted in a higher cyto- and genotoxicity in Caco-2, HT-29 and HCT-116 cell lines. High-fat compared to low fat beef digests contained approximately 10-fold higher LOP concentrations (all P < 0.001), and induced higher cytotoxicity (P < 0.001). During digestion of the high-fat product, phenolic acids (gallic, ferulic, chlorogenic, and caffeic acid) displayed either pro-oxidant or antioxidant behavior at lower and higher doses respectively, whereas ascorbic acid was pro-oxidant at all doses, and the lipophilic reducing compounds (alpha-tocopherol, quercetin, and silibinin) all exerted a clear antioxidant effect. During digestion of the low-fat product, the hydrophilic compounds and quercetin were antioxidant. Decreases or increases in LOP concentrations amounted to 100% change versus controls. PMID- 26836478 TI - Rhodanese incorporated in Langmuir and Langmuir-Blodgett films of dimyristoylphosphatidic acid: Physical chemical properties and improvement of the enzyme activity. AB - Preserving the catalytic activity of enzymes immobilized in bioelectronics devices is essential for optimal performance in biosensors. Therefore, ultrathin films in which the architecture can be controlled at the molecular level are of interest. In this work, the enzyme rhodanese was adsorbed onto Langmuir monolayers of the phospholipid dimyristoylphosphatidic acid and characterized by surface pressure-area isotherms, polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), and Brewster angle microscopy (BAM). The incorporation of the enzyme (5% in mol) in the lipid monolayer expanded the film, providing small surface domains, as visualized by BAM. Also, amide bands could be identified in the PM-IRRAS spectra, confirming the presence of the enzyme at the air-water interface. Structuring of the enzyme into alpha-helices was identified in the mixed monolayer and was preserved when the film was transferred from the liquid interface to solids supports as Langmuir-Blodgett (LB) films. The enzyme lipid LB films were then characterized by fluorescence spectroscopy, PM-IRRAS, and atomic force microscopy. Measurements of the catalytic activity towards cyanide showed that the enzyme accommodated in the LB films preserved more than 87% of the enzyme activity in relation to the homogeneous medium. After 1 month, the enzyme in the LB film maintained 85% of the activity in contrast to the homogeneous medium, which 24% of the enzyme activity was kept. The method presented in this work not only points to an enhanced catalytic activity toward cyanide, but also may explain why certain film architectures exhibit an improved performance. PMID- 26836479 TI - Antifouling coatings based on covalently cross-linked agarose film via thermal azide-alkyne cycloaddition. AB - Coatings based on thin films of agarose-poly(ethylene glycol) (Agr-PEG) cross linked systems are developed as environmentally-friendly and fouling-resistant marine coatings. The Agr-PEG cross-linked systems were prepared via thermal azide alkyne cycloaddition (AAC) using azido-functionalized Agr (AgrAz) and activated alkynyl-containing poly(2-propiolamidoethyl methacrylate-co-poly(ethylene glycol)methyl ether methacrylate) P(PEMA-co-PEGMEMA) random copolymers as the precursors. The Agr-PEG cross-linked systems were further deposited onto a SS surface, pre-functionalized with an alkynyl-containing biomimetic anchor, dopamine propiolamide, to form a thin film after thermal treatment. The thin film coated SS surfaces can effectively reduce the adhesion of marine algae and the settlement of barnacle cyprids. Upon covalent cross-linking, the covalently cross linked Agr-PEG films coated SS surfaces exhibit good stability in flowing artificial seawater, and enhanced resistance to the settlement of barnacle cyprids, in comparison to that of the surfaces coated with physically cross linked AgrAz films. PMID- 26836481 TI - So Much Cholesterol: the unrecognized importance of smooth muscle cells in atherosclerotic foam cell formation. AB - PURPOSE OF REVIEW: Smooth muscle cells (SMCs) form the thickened intimal layer in atherosclerosis-prone arteries in early life, and provide the initial site for retention and uptake of atherogenic lipoproteins. Here we review current knowledge regarding the importance of SMCs in the deposition of cholesterol in atherosclerotic plaque. RECENT FINDINGS: SMCs were found to comprise at least 50% of total foam cells in human coronary artery atherosclerosis, and exhibit a selective loss of expression of the cholesterol efflux promoter ATP-binding cassette transporter A1. Cholesterol loading induced a loss of SMC gene expression and an increase in macrophage and proinflammatory marker expression by cultured mouse and human arterial SMCs, with reversal of these effects upon removal of the excess cholesterol. Mice engineered to track all cells of SMC lineage indicated that, at most, SMCs make up about one-third of total cells in atherosclerotic plaque in these animals. SUMMARY: SMCs appear to be the origin of the majority of foam cells in human atherosclerotic plaque. Recent studies suggest a renaissance of research on the role of SMCs in atherosclerosis is needed to make the next leap forward in the prevention and treatment of this disease. PMID- 26836480 TI - Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy. AB - Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin. PMID- 26836482 TI - Polyphenols and Polypeptides in Chinese Rice Wine Inhibit Homocysteine-induced Proliferation and Migration of Vascular Smooth Muscle Cells. AB - The beneficial effect of Chinese rice wine on atherosclerosis has been proved, but the exact components that have the cardiovascular protective effect are still unknown. This study aimed to explore the exact ingredients in Chinese rice wine that could inhibit homocysteine (Hcy)-induced vascular smooth muscle cell (VSMC) proliferation and migration. VSMCs were divided into 7 groups: control, Hcy (1 mmol/L), Hcy + oligosaccharide, Hcy + polypeptides, Hcy + polyphenols, Hcy + alcohol, and Hcy + Chinese rice wine. methyl thiazolyl tetrazolium (MTT) assay, Transwell chambers, and wound-healing assay were used to test the proliferation and migratory ability of the VSMCs. Western blot and gelatin zymography were used to investigate the expressions and activities of metal matrix proteinase 2/9 (MMP 2/9) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in VSMCs. Polypeptides and polyphenols in the Chinese rice wine reduced the proliferation and migration ability of the VSMCs. Furthermore, they also decreased the expression and activity of MMP-2/9 but had no obvious impact on the expression of TIMP-2 in each group. This study further confirms that polypeptides and polyphenols in the Chinese rice wine could inhibit Hcy-induced proliferation and migration of VSMCs and maintain the balance between matrix metalloproteinases (MMPs) and TIMPs. PMID- 26836483 TI - Condensation Reactions of Chlorophosphanes with Chalcogenides. AB - A high-yielding and facile synthesis for diphosphane monochalcogenides (1(Ch)((R))) and their constitutional isomers, diphosphanylchalcoganes (2(Ch)((R))), was developed, featuring a condensation reaction between chlorophosphanes (R2PCl) and sodium chalcogenides (Na2Ch, Ch = S, Se, (Te)). The optimized protocol selectively yields either 1(Ch)((R)) (R2(Ch)PPR2) or 2(Ch)((R)) (Ch(PR2)2) depending upon the steric demand of the substituents R. Reaction pathways consistent with the distinct reaction outcomes are proposed. The application of 1(Ch)((R)) and 2(Ch)((R)) as an interesting class of ligands is exemplarily demonstrated by the preparation of selected transition metal complexes. PMID- 26836484 TI - Adjacent Segment Degeneration Versus Disease After Lumbar Spine Fusion for Degenerative Pathology: A Systematic Review With Meta-Analysis of the Literature. AB - STUDY DESIGN: A systematic review. OBJECTIVE: The purpose of this study was to review the published literature to estimate rates and identify risk factors for adjacent segment degeneration (ASDeg) and adjacent segment disease (ASDis) after lumbar fusion. SUMMARY OF BACKGROUND DATA: Arthrodesis remains a common intervention for the surgical treatment of degenerative spinal disease. Clinical studies have demonstrated variability in the rates of adjacent segment pathology after lumbar fusion. METHODS: This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Symptoms of ASDis were distinguished and defined by the need for a revision surgery procedure to address adjacent level pathology. We searched MEDLINE, EMBASE, Cochrane Library, and CINAHL databases. Extracted data included average patient age, average time to follow-up, type of intervention, potential risk factors, and ASDeg and ASDis incidence. Funnel and forest plots were used to describe heterogeneity and meta-regression to estimate pooled incidence of ASDeg and ASDis. RESULTS: A total of 31 articles with 4206 patients were included for analysis. Combining all extractable data, the overall pooled incidence of ASDeg was 5.9% per year (95% CI, 4.8%, 7.2%), and ASDis was 1.8% (95% CI, 1.3%, 2.4%) per year. The incidence of ASDeg is higher with more motion segments. Sex, age, segmental sagittal alignment, fusion methods, and instrumentation were not associated with an increased risk of ASDeg or ASDis. Radiographic ASDeg did not show strong correlation with clinical outcomes. CONCLUSIONS: The prevalence of ASDeg and ASDis has been variably reported in the literature, and fusion length is the factor most significantly associated with adjacent segment pathology. In guiding surgical strategies to avoid adjacent segment pathology, limiting the number of levels fused may have a greater impact than changes in fusion strategies. PMID- 26836485 TI - Determination of glutaredoxin enzyme activity and protein S-glutathionylation using fluorescent eosin-glutathione. AB - Glutaredoxins catalyze glutathione-dependent disulfide oxidoreductions, particularly reduction of glutathione (GSH)-protein mixed disulfides. Mammalian glutaredoxins are present in the cytosol/nucleus as Grx1 or in mitochondria as Grx2a. Here we describe di-eosin-glutathione disulfide (Di-E-GSSG) as a new tool to study glutaredoxin (Grx) activity. Di-E-GSSG has almost no fluorescence in its disulfide form due to self-quenching, whereas the reduced form (E-GSH) has a large fluorescence emission at 545 nm after excitation at 520 nm. Di-E-GSSG was a very poor substrate for glutathione reductase, but we discovered that the molecule was an excellent substrate for glutaredoxin in a coupled assay system with GSH, nicotinamide adenine dinucleotide phosphate (NADPH), and glutathione reductase or with lipoamide, NADH, and lipoamide dehydrogenase. In addition, Di-E GSSG was used to glutathionylate the free SH group of bovine serum albumin (BSA), yielding eosin-glutathionylated BSA (E-GS-BSA) readily observed in ultraviolet (UV) light. E-GS-BSA also displayed a quenched fluorescence, and its Grx catalyzed reduction could be followed by the formation of E-GSH by fluorescence emission using microtiter plates. This way of measuring Grx activity provided an ultrasensitive method that detected Grx1 and Grx2 at picomolar levels. Human Grx1 was readily quantified in 40 MUl of plasma and determined to be 680 +/- 208 pM in healthy controls. PMID- 26836486 TI - Rapid and inexpensive species differentiation using a multiplex real-time polymerase chain reaction high-resolution melt assay. AB - We demonstrate a method for developing real-time polymerase chain reaction (PCR) high-resolution melt (HRM) assays to identify multiple species present in a mixture simultaneously using LCGreen Plus and melt temperatures. Highly specific PCR primers are designed to yield amplicons with different melt temperatures for simple routine species identification compared with differentiating melt curve kinetics traces or difference plots. This method is robust and automatable, and it leads to savings in time and reagent costs, is easily modified to probe any species of interest, eliminates the need for post-PCR gel or capillary electrophoresis in routine assays, and requires no expensive dye-labeled primers. PMID- 26836487 TI - Darwin's Pangenesis as a molecular theory of inherited diseases. AB - Darwin spent much time and effort on the study of inherited diseases and the role of environment in disease development. To explain inherited diseases and a considerable variety of other hereditary phenomena, he formulated a Pangenesis hypothesis, assuming that cells could shed many kinds of molecules capable of diffusion from cell to cell, circulation throughout the body, incorporation into recipient cells, and transmission from parents to offspring. His Pangenesis is now supported by the discovery of circulating DNA, mobile RNAs and prions, and might provide an alternative molecular mechanism underlying the inherited diseases. PMID- 26836488 TI - Real time tracking in liver SBRT: comparison of CyberKnife and Vero by planning structure-based gamma-evaluation and dose-area-histograms. AB - The purpose of this study was to evaluate and compare two clinical tracking systems for radiosurgery with regard to their dosimetric and geometrical accuracy in liver SBRT: the robot-based CyberKnife and the gimbal-based Vero. Both systems perform real-time tumour tracking by correlating internal tumour and external surrogate motion. CyberKnife treatment plans were delivered to a high resolution 2D detector array mounted on a 4D motion platform, with the platform simulating (a) tumour motion trajectories extracted from the corresponding CyberKnife predictor log files and (b) the tumour motion trajectories with superimposed baseline-drift. Static reference and tracked dose measurements were compared and dosimetric as well as geometrical uncertainties analyzed by a planning structure based evaluation. For (a), gamma-passing rates inside the CTV (gamma-criteria of 1% / 1 mm) ranged from 95% to 100% (CyberKnife) and 98% to 100% (Vero). However, dosimetric accuracy decreases in the presence of the baseline-drift. gamma passing rates for (b) ranged from 26% to 92% and 94% to 99%, respectively; i.e. the effect was more pronounced for CyberKnife. In contrast, the Vero system led to maximum dose deviations in the OAR between +1.5 Gy to +6.0 Gy (CyberKnife: +0.5 Gy to +3.5 Gy). Potential dose shifts were interpreted as motion-induced geometrical tracking errors. Maximum observed shift ranges were -1.0 mm to +0.7 mm (lateral) /-0.6 mm to +0.1 mm (superior-inferior) for CyberKnife and -0.8 mm to +0.2 mm /-0.8 mm to +0.4 mm for Vero. These values illustrate that CyberKnife and Vero provide high precision tracking of regular breathing patterns. Even for the modified motion trajectory, the obtained dose distributions appear to be clinical acceptable with regard to literature QA gamma-criteria of 3% / 3 mm. PMID- 26836489 TI - Disagreement Between the Structure of the dTpT Thymine Pair Determined by NMR and Molecular Dynamics Simulations Using Amber 14 Force Fields. AB - We report a disagreement between the predicted structures of the dTpT thymine pair (thymidylyl(3' -> 5')thymidine) using nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations using the AMBER ff14SB and ff14 + epsilon/zetaOL1 + chiOL4 force fields for DNA. The NMR structure was determined using NOE couplings to thymine's H6 and J(HH) couplings between sugar protons. The MD simulation used replica exchange methods to produce converged statistics in a 500 ns trajectory. NMR data indicate that both thymine nucleotides in the pair display an anti conformation of B-DNA, while the MD simulations predict a structure in which the 5'-thymine is flipped into a syn conformation and the 3'-thymine is in an anti conformation. The syn conformation of the 5'-thymine predicted by MD appears by a ~ 180-deg flip of the glycosidic angle in comparison to the B-form anti structure. Differences in the distortion of the sugar pucker between 5'-thymine and 3'-thymine further highlighted the surprisingly different conformation of the 5'- and 3'-ends. While both MD and NMR indicate the deoxyribose sugars to be primarily in the 2'-endo conformation typical of B-form DNA, the MD simulations predict a more twisted conformation (2' endo/1'-exo) for the 5'-sugar and significant flexibility of C3' of the 3'-sugar. We conclude that the current AMBER force field does not accurately predict the conformation of single-stranded thymine, in agreement with previous work investigating single-stranded DNA. PMID- 26836490 TI - The Many Dimensions of Diet Breadth: Phytochemical, Genetic, Behavioral, and Physiological Perspectives on the Interaction between a Native Herbivore and an Exotic Host. AB - From the perspective of an herbivorous insect, conspecific host plants are not identical, and intraspecific variation in host nutritional quality or defensive capacity might mediate spatially variable outcomes in plant-insect interactions. Here we explore this possibility in the context of an ongoing host breadth expansion of a native butterfly (the Melissa blue, Lycaeides melissa) onto an exotic host plant (alfalfa, Medicago sativa). We examine variation among seven alfalfa populations that differed in terms of colonization by L. melissa; specifically, we examined variation in phytochemistry, foliar protein, and plant population genetic structure, as well as responses of caterpillars and adult butterflies to foliage from the same populations. Regional patterns of alfalfa colonization by L. melissa were well predicted by phytochemical variation, and colonized patches of alfalfa showed a similar level of inter-individual phytochemical diversity. However, phytochemical variation was a poor predictor of larval performance, despite the fact that survival and weight gain differed dramatically among caterpillars reared on plants from different alfalfa populations. Moreover, we observed a mismatch between alfalfa supporting the best larval performance and alfalfa favored by ovipositing females. Thus, the axes of plant variation that mediate interactions with L. melissa depend upon herbivore life history stage, which raises important issues for our understanding of adaptation to novel resources by an organism with a complex life history. PMID- 26836491 TI - The association of severe aortic stenosis and narrow aortic root in a young patient--What is the etiology: Rheumatic valvulitis or Lambl's excrescences? PMID- 26836492 TI - Association of ST elevation with not only post-infarction ischemic apical aneurysm but also apical aneurysm associated with hypertrophic cardiomyopathy. PMID- 26836493 TI - "Rare" diseases: Motivated patients make the difference. PMID- 26836495 TI - Efficacy of Desmopressin to Treat Nocturnal Polyuria in Elderly Men: Effects on Sleep Quality. AB - BACKGROUND: We investigated the efficacy of desmopressin in elderly patients with nocturnal polyuria (NP) to evaluate its effects on sleep quality. METHODS: Patients with NP (defined as the nighttime urine production >33% of total 24-hour urine volume determined from a frequency-volume chart) were recruited. Desmopressin (0.2 mg) was treated orally at bedtime for 12 weeks. The participants completed the Medical Outcomes Study (MOS) Sleep Scale. RESULTS: The mean patient age was 62.7 +/- 13.0 (range 42-78 years). The mean symptom duration was 42.2 +/- 39.7 months. The number of nocturia episodes (from 3.49 +/- 1.83 to 2.03 +/- 1.35, p = 0.01), nocturnal urine volume (p = 0.01), NP index (p = 0.01), and nocturia index (p = 0.01) decreased significantly after treatment with desmopressin. Among the MOS Sleep Scale categories, hours slept/night (p = 0.042), shortness of breath (p = 0.019), and adequacy of sleep (p = 0.001) changed significantly with a decrease in the number of nocturia episodes. Adverse events were mild. CONCLUSIONS: Desmopressin is an effective treatment for NP and improved sleep quality in elderly men. PMID- 26836494 TI - Fertility and pregnancy in the Fontan population. AB - BACKGROUND: Women with a Fontan circulation are deemed at significantly increased risk of maternal morbidity and mortality during pregnancy. Publications describe a small number of pregnancies worldwide and a high rate of miscarriage. We compiled the experience of women enrolled in the Australia and New Zealand Fontan (ANZ) Registry with regard to menarche, contraceptive use, pregnancy advice and pregnancy outcomes. METHODS: Women within the ANZ Fontan Registry were contacted and asked to consent to receiving sequential questionnaires. RESULTS: 156 women >= 18 years of age (including 4 deceased individuals) were identified, 101 women consented and 97 completed the initial questionnaire. Women were aged (median) 25 years (23-32); menarche occurred at a median 14 years (13-16). A wide variety of contraceptive methods was reported. 81% of women reported having received advice that pregnancy carried an increased risk or was inadvisable. Pregnancy was reported in a minority (n=27). Miscarriage (42.5%) and termination (7.5%) accounted for half the pregnancy outcomes and the babies were born early (median 31.5 weeks) and small (median 1350 g). Maternal complications of bleeding, arrhythmia and heart failure were reported with no early maternal mortality. CONCLUSIONS: In women with a Fontan circulation the fertility onset is delayed and pregnancy has a higher rate of miscarriage. Successful pregnancy resulted in small and premature babies. Significant maternal morbidity occurred. Whether pregnancy with its volume loading has an adverse effect on the long-term outcome of women with a single ventricle remains to be elucidated. PMID- 26836496 TI - Performance of AGO score for secondary cytoreduction in a high-volume U.S. center. AB - OBJECTIVES: Determine the predictive value of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score, and prognostic factors for survival, in patients undergoing secondary cytoreductive surgery (SCS) for recurrent ovarian cancer in a high-volume U.S. center. METHODS: Medical records of women undergoing SCS between 12/1/1998 and 12/31/2013 were reviewed. Women with no gross residual disease (RD0) at primary surgery, ECOG performance status (PS) <=1 at recurrence, and no ascites on CT at recurrence were classified as AGO score positive. Women with incomplete information to determine the AGO score were excluded. Overall survival (OS) and progression-free survival (PFS) following SCS, respectively, were estimated from multivariable Cox proportional hazards models. RESULTS: 192 women met inclusion criteria. Median disease-free interval (DFI) was 1.9years (IQR, 1.0-3.5). Of the 102 (53.1%) AGO score positive cases, 84.3% (95% CI, 77.3 91.4%) achieved RD0 at SCS. However, 64.4% of AGO score negative cases also reached RD0. Patients with RD0 after SCS survived longer (median OS, 5.4years) vs. RD <=1cm (2.4years) vs. RD >1cm (1.3years) (p<0.001). Median PFS was also longer in patients with RD0 (1.5years) vs. RD <=1cm (0.9years) vs. RD >1cm (1.0years) (p=0.001). Among those with RD0 at SCS, AGO score was not associated with survival benefit, however, number of disease sites at recurrence, ECOG PS at recurrence, and DFI were associated with OS and PFS. CONCLUSIONS: AGO score can identify patients with a high likelihood of complete secondary cytoreduction and improved survival. However, most AGO score negative cases were also completed resected at SCS. Additional refinement of the score is needed to exclude women from SCS. PMID- 26836497 TI - Why We Still Need More Research on the Epidemiology of Huntington's Disease. PMID- 26836499 TI - Synthesis of Polysubstituted 2-Iodoindenes via Iodonium-Induced Cyclization of Arylallenes. AB - A new chemoselective iodocarbocyclization of allenyl arenes was developed leading to the formation of 2-iodoindenes. In acetonitrile or nitromethane, electrophilic sources of iodine cations react selectively with the C2-C3 double bond of 1 arylallenes to give, after anti nucleophilic attack of the aromatic ring, 2 iodoindene products in high yields. Variations of the allenic skeletons revealed the high 5-endo selectivity and some competitive pathways of cyclization. Postfunctionalization reactions of the carbon-iodine bond, via Pd- and Cu-cross couplings, gave rise to substituted indenes in good to excellent yields. PMID- 26836498 TI - The application of molecular modelling in the safety assessment of chemicals: A case study on ligand-dependent PPARgamma dysregulation. AB - The aim of this paper was to provide a proof of concept demonstrating that molecular modelling methodologies can be employed as a part of an integrated strategy to support toxicity prediction consistent with the mode of action/adverse outcome pathway (MoA/AOP) framework. To illustrate the role of molecular modelling in predictive toxicology, a case study was undertaken in which molecular modelling methodologies were employed to predict the activation of the peroxisome proliferator-activated nuclear receptor gamma (PPARgamma) as a potential molecular initiating event (MIE) for liver steatosis. A stepwise procedure combining different in silico approaches (virtual screening based on docking and pharmacophore filtering, and molecular field analysis) was developed to screen for PPARgamma full agonists and to predict their transactivation activity (EC50). The performance metrics of the classification model to predict PPARgamma full agonists were balanced accuracy=81%, sensitivity=85% and specificity=76%. The 3D QSAR model developed to predict EC50 of PPARgamma full agonists had the following statistical parameters: q2cv=0.610, Nopt=7, SEPcv=0.505, r2pr=0.552. To support the linkage of PPARgamma agonism predictions to prosteatotic potential, molecular modelling was combined with independently performed mechanistic mining of available in vivo toxicity data followed by ToxPrint chemotypes analysis. The approaches investigated demonstrated a potential to predict the MIE, to facilitate the process of MoA/AOP elaboration, to increase the scientific confidence in AOP, and to become a basis for 3D chemotype development. PMID- 26836500 TI - Survival of tunneled hemodialysis catheters after percutaneous placement. AB - BACKGROUND: Tunneled catheters are becoming increasingly used as a permanent dialysis access. Easy way of insertion and good long-term patency make them competitive to fistulas in some groups of patients. METHODS: Late complications and survival of 180 tunneled catheters inserted from June 2010 to December 2013 in 171 unselected hemodialysis patients were analyzed. RESULTS: The cumulative time of observation was 2103.5 patient-months and median observation was 9 months (range of 0.5-45 months). Only 19 out of 180 catheters were removed due to complications (12 for infections, 4 due to malfunction and 3 because of mechanical damage). Majority of catheters were removed electively: 27 after maturation of arterio-venous fistula (AVF), 4 after kidney transplant, 5 after transfer to peritoneal dialysis and 3 due to the recovery of renal function. At the end of the observation, 58 catheters were still in use and 64 patients had died with functioning catheter. When censored for elective catheter removal and patient death, 88.2% of catheters survived for 1 year. Catheter survival was significantly better in older patients (over 65 years, in comparison to patients < 65 years, p = 0.046). CONCLUSIONS: Nearly 90% of all inserted catheters gave reliable dialysis access as long as it was needed. Among them, over 30% of the inserted catheters were in use at the end of the observation period, and over 30% of patients had died with a functioning catheter. The results of tunneled catheters survival are encouraging and they should be taken into consideration during decision-making on vascular access, especially in the older patients. PMID- 26836501 TI - A comprehensive catalog of the lysine-acetylation targets in rice (Oryza sativa) based on proteomic analyses. AB - Lysine acetylation is a dynamic and reversible post-translational modification that plays an important role in the gene transcription regulation. Here, we report high quality proteome-scale data for lysine-acetylation (Kac) sites and Kac proteins in rice (Oryza sativa). A total of 1337 Kac sites in 716 Kac proteins with diverse biological functions and subcellular localizations were identified in rice seedlings. About 42% of the sites were predicted to be localized in the chloroplast. Seven putative acetylation motifs were detected. Phenylalanine, located in both the upstream and downstream of the Kac sites, is the most conserved amino acid surrounding the regions. In addition, protein interaction network analysis revealed that a variety of signaling pathways are modulated by protein acetylation. KEGG pathway category enrichment analysis indicated that glyoxylate and dicarboxylate metabolism, carbon metabolism, and photosynthesis pathways are significantly enriched. Our results provide an in depth understanding of the acetylome in rice seedlings, and the method described here will facilitate the systematic study of how Kac functions in growth, development, and abiotic and biotic stress responses in rice and other plants. BIOLOGICAL SIGNIFICANCE: Rice is one of the most important crops consumption and is a model monocot for research. In this study, we combined a highly sensitive immune-affinity purification method (used pan anti-acetyl-lysine antibody conjugated agarose for immunoaffinity acetylated peptide enrichment) with high resolution LC-MS/MS. In total, we identified 1337 Kac sites on 716 Kac proteins in rice cells. Bioinformatic analysis of the acetylome revealed that the acetylated proteins are involved in a variety of cellular functions and have diverse subcellular localizations. We also identified seven putative acetylation motifs in the acetylated proteins of rice. In addition, protein interaction network analysis revealed that a variety of signaling pathways were modulated by protein acetylation. KEGG pathway category enrichment analysis indicated that glyoxylate and dicarboxylate metabolism, carbon metabolism, and photosynthesis pathways were significantly enriched. To our knowledge, the number of Kac sites we identified was 23-times greater and the number of Kac proteins was 16-times greater than in a previous report. Our results provide an in-depth understanding of the acetylome in rice seedlings, and the method described here will facilitate the systematic study of how Kac functions in growth, development and responses to abiotic and biotic stresses in rice or other plants. PMID- 26836502 TI - miRNA expression profiles and retinal blood vessel calibers are associated with short-term particulate matter air pollution exposure. AB - INTRODUCTION: Air pollution, a risk factor for cardiovascular diseases, can exert its effects through the microcirculation. Retinal blood vessel width is considered a marker for microvascular health and is associated with short-term PM10 exposure. microRNAs are key regulators of complex biological processes in cardiovascular health and disease and miRNA expression can be affected by air pollution exposure. Studies investigating the effect of ambient air pollution exposure on miRNA expression in combination with an assessment of the microvasculature do not exist. METHODS: 50 healthy adults (50% women, 23-58 years old) were examined once a month from December 2014 until April 2015 in Flanders (Belgium). Fundus photos and venous blood samples were collected during the study visits. PM10 data were obtained from a nearby monitoring station. Image analysis was used to calculate the width of retinal blood vessels, represented as the Central Retinal Arteriolar/Venular Equivalent (CRAE/CRVE). Total miRNA was isolated from blood and the expression of miR-21, -146a and, -222 were measured using quantitative real-time PCR. Mixed models were used for statistical analysis. RESULTS: Each short-term increase of 10ug/m(3) PM10 during the 24h preceding the study visit was associated with a 0.58um decrease (95% CI: -1.16, 0.0005; p=0.056) in CRAE, a 0.99um increase (95% CI: 0.18, 1.80; p=0.021) in CRVE, a 6.6% decrease (95% CI: -11.07, -2.17; p=0.0038) in miR-21 expression and a 6.7% decrease (95% CI: -10.70, -2.75; p=0.0012) in miR-222 expression. Each 10% increase in miR-21 was associated with a 0.14um increase (95% CI: 0.0060, 0.24; p=0.046) in CRAE whereas a similar increase in miR-222 expression was associated with a 0.28um decrease (95% CI: -0.50, -0.062; p=0.016) in CRVE. These associations were also found in exposure windows ranging from 2h to 1 week. Finally, we observed that the association between PM10 exposure and CRAE was mediated by miRNA-21 expression. CONCLUSION: PM10 exposure was associated with retinal arteriolar narrowing and venular widening. PM10 exposure affected miRNAs that are involved in inflammatory and oxidative stress pathways. We suggest that miRNA changes may be relevant to explain the association between PM10 and retinal vessel calibers. PMID- 26836503 TI - PRC2 and SWI/SNF Chromatin Remodeling Complexes in Health and Disease. AB - The dynamic structure of histones and DNA, also known as chromatin, is regulated by two classes of enzymes: those that mediate covalent modifications on either histone proteins or DNA and those that use the energy generated by ATP hydrolysis to mechanically alter chromatic structure. Both classes of enzymes are often found in large protein complexes. In this review, we describe two such complexes: polycomb repressive complex 2 (PRC2), with the protein methyltransferase EZH2 as its catalytic subunit, and the ATP-dependent chromatin remodeler switch/sucrose non-fermentable (SWI/SNF). EZH2 catalyzes the methylation of lysine 27 on histone H3, a covalent chromatin modification that is associated with repressed heterochromatin. The catalytic activity of SWI/SNF, in contrast, leads to a state of open chromatin associated with active transcription. In this review, we discuss the biochemical properties of both complexes, outline the principles of their regulation, and describe their opposing roles in normal development, which can be perturbed in disease settings such as cancer. PMID- 26836504 TI - Fish Consumption and Premenstrual Syndrome and Dysphoric Disorder in Japanese Collegiate Athletes. AB - STUDY OBJECTIVE: To determine the specific characteristics of premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) in Japanese collegiate athletes, with a focus on their fish consumption. DESIGN: Cross-sectional study. SETTING: A university in Osaka, the largest city in western Japan. PARTICIPANTS AND INTERVENTIONS: The participants were 312 female collegiate students. The study group was composed of 200 students who were members of sport clubs, and the control (nonathletes) group was composed of 112 members of cultural clubs. MAIN OUTCOME MEASURES: Premenstrual symptoms and social activities. RESULTS: The prevalence of moderate to severe PMS and PMDD in the study group was the same as in nonathletes. The prominent feature of premenstrual symptoms in athletes was that the severities of 'physical symptoms' and 'performance in training or competition' were much greater than those of nonathletes (P = .003 and P = .002, Mann-Whitney U test). There was a greater effect of PMS and PMDD on athletes, affecting their physical symptoms and performance compared with nonathletes. In terms of dietary habits, 'fish or dried fish' consumption was associated with a decreased risk of poor performance in athletes (odds ratio, 0.61; 95% confidence interval, 0.40-0.92). CONCLUSION: The results from this study indicate that fish consumption might be positively associated with the relief of PMS/PMDD-induced athletic disturbance. PMID- 26836505 TI - Cesarean Delivery in Adolescents. AB - STUDY OBJECTIVE: To examine the effect of maternal age on indication for primary cesarean delivery in low-risk nulliparous women. DESIGN: Retrospective cohort study. SETTING: Urban academic tertiary care center. PARTICIPANTS: Nulliparous women younger than 35 years of age delivering vertex-presenting singletons at term. INTERVENTIONS: Participants underwent spontaneous, operative or cesarean delivery. MAIN OUTCOME MEASURES: Mode of delivery, indication, and timing of cesarean delivery. RESULTS: Adolescents were half as likely to undergo cesarean delivery overall (odds ratio [OR], 0.48; 95% confidence interval [CI], 0.43 0.54), and more than one-third less likely to undergo cesarean delivery in labor (OR, 0.59; 95% CI, 0.53-0.66). Adjustment for potential confounders did not alter the strength of these associations. Adolescents were half as likely to undergo cesarean delivery for failure to progress (OR, 0.49; 95% CI, 0.43-0.54). There was no difference in the odds of cesarean delivery for nonreassuring fetal status (OR, 0.91; 95% CI, 0.77-1.06), or genital herpes (OR, 1.44; 95% CI, 0.57-3.68). Induction, macrosomia, oxytocin augmentation, and any labor complication were all associated with increased risk of cesarean delivery. There was no difference in the duration of second stage for adolescents who delivered by cesarean delivery compared with adults (240.0 vs 237.7 minutes; P = .84), but adolescents who delivered vaginally had a second stage that was one-third shorter than adults (62.5 vs 100.3 minutes; P < .001). CONCLUSION: Adolescents are half as likely to undergo primary cesarean delivery overall, and 40% less likely to undergo a primary cesarean delivery in labor, even after adjustment for multiple maternal, neonatal, and labor characteristics. This difference is not explained by differences in the duration of the second stage of labor. PMID- 26836506 TI - Validation of the Mass-Extraction-Window for Quantitative Methods Using Liquid Chromatography High Resolution Mass Spectrometry. AB - A paradigm shift is underway in the field of quantitative liquid chromatography mass spectrometry (LC-MS) analysis thanks to the arrival of recent high resolution mass spectrometers (HRMS). The capability of HRMS to perform sensitive and reliable quantifications of a large variety of analytes in HR-full scan mode is showing that it is now realistic to perform quantitative and qualitative analysis with the same instrument. Moreover, HR-full scan acquisition offers a global view of sample extracts and allows retrospective investigations as virtually all ionized compounds are detected with a high sensitivity. In time, the versatility of HRMS together with the increasing need for relative quantification of hundreds of endogenous metabolites should promote a shift from triple-quadrupole MS to HRMS. However, a current "pitfall" in quantitative LC HRMS analysis is the lack of HRMS-specific guidance for validated quantitative analyses. Indeed, false positive and false negative HRMS detections are rare, albeit possible, if inadequate parameters are used. Here, we investigated two key parameters for the validation of LC-HRMS quantitative analyses: the mass accuracy (MA) and the mass-extraction-window (MEW) that is used to construct the extracted ion-chromatograms. We propose MA-parameters, graphs, and equations to calculate rational MEW width for the validation of quantitative LC-HRMS methods. MA measurements were performed on four different LC-HRMS platforms. Experimentally determined MEW values ranged between 5.6 and 16.5 ppm and depended on the HRMS platform, its working environment, the calibration procedure, and the analyte considered. The proposed procedure provides a fit-for-purpose MEW determination and prevents false detections. PMID- 26836507 TI - Linking sub-cellular biomarkers to embryo aberrations in the benthic amphipod Monoporeia affinis. AB - To adequately assess and monitor environmental status in the aquatic environment a broad approach is needed that integrates physical variables, chemical analyses and biological effects at different levels of the biological organization. Embryo aberrations in the Baltic Sea key species Monoporeia affinis can be induced by both metals and organic substances as well as by hypoxia, increasing temperatures and malnutrition. This amphipod has therefore been used for more than three decades as a biological effect indicator in monitoring and assessment of chemical pollution and environmental stress. However, little is known about the sub cellular mechanisms underlying embryo aberrations. An improved mechanistic understanding may open up the possibility of including sub-cellular alterations as sensitive warning signals of stress-induced embryo aberrations. In the present study, M. affinis was exposed in microcosms to 4 different sediments from the Baltic Sea. After 88-95 days of exposure, survival and fecundity were determined as well as the frequency and type of embryo aberrations. Moreover, oxygen radical absorption capacity (ORAC) was assayed as a proxy for antioxidant defense, thiobarbituric acid reactive substances (TBARS) level as a measure of lipid peroxidation and acetylcholinesterase (AChE) activity as an indicator of neurotoxicity. The results show that AChE and ORAC can be linked to the frequency of malformed embryos and arrested embryo development. The occurrence of dead broods was significantly associated with elevated TBARS levels. It can be concluded that these sub-cellular biomarkers are indicative of effects that could affect Darwinian fitness and that oxidative stress is a likely mechanism in the development of aberrant embryos in M. affinis. PMID- 26836508 TI - High hydrostatic pressure influences the in vitro response to xenobiotics in Dicentrarchus labrax liver. AB - Hydrostatic pressure (HP) increases by about 1 atmosphere (0.1MPa) for each ten meter depth increase in the water column. This thermodynamical parameter could well influence the response to and effects of xenobiotics in the deep-sea biota, but this possibility remains largely overlooked. To grasp the extent of HP adaptation in deep-sea fish, comparative studies with living cells of surface species exposed to chemicals at high HP are required. We initially conducted experiments with precision-cut liver slices of a deep-sea fish (Coryphaenoides rupestris), co-exposed for 15h to the aryl hydrocarbon receptor (AhR) agonist 3 methylcholanthrene at HP levels representative of the surface (0.1MPa) and deep sea (5-15MPa; i.e., 500-1500m depth) environments. The transcript levels of a suite of stress-responsive genes, such as the AhR battery CYP1A, were subsequently measured (Lemaire et al., 2012; Environ. Sci. Technol. 46, 10310 10316). Strikingly, the AhR agonist-mediated increase of CYP1A mRNA content was pressure-dependently reduced in C. rupestris. Here, the same co-exposure scenario was applied for 6 or 15h to liver slices of a surface fish, Dicentrarchus labrax, a coastal species presumably not adapted to high HP. Precision-cut liver slices of D. labrax were also used in 1h co-exposure studies with the pro-oxidant tert butylhydroperoxide (tBHP) as to investigate the pressure-dependence of the oxidative stress response (i.e., reactive oxygen production, glutathione and lipid peroxidation status). Liver cells remained viable in all experiments (adenosine triphosphate content). High HP precluded the AhR agonist-mediated increase of CYP1A mRNA expression in D. labrax, as well as that of glutathione peroxidase, and significantly reduced that of heat shock protein 70. High HP (1h) also tended per se to increase the level of oxidative stress in liver cells of the surface fish. Trends to an increased resistance to tBHP were also noted. Whether the latter observation truly reflects a protective response to oxidative stress will be addressed in future co-exposure studies with both surface and deep sea fish liver cells, using additional pro-oxidant chemicals. Altogether, data on CYP1A inducibility with D. labrax and C. rupestris support the view that high HP represses AhR signaling in marine fishes, and that only species adapted to thrive in the deep-sea have evolved the molecular adaptations necessary to counteract to some extent this inhibition. PMID- 26836509 TI - Measuring Apoptosis by Microscopy and Flow Cytometry. AB - Apoptosis is a mode of programmed cell death that plays an important role during development and in the maintenance of tissue homeostasis. Numerous physiological as well as pathological stimuli trigger apoptosis such as engagement of Fas, TRAIL, or TNF receptors, growth factor deprivation, hypoxia, or exposure to cytotoxic drugs. Apoptosis is coordinated from within by members of the caspase family of cysteine proteases that, upon activation, trigger a series of morphological changes including cell shrinkage, extensive plasma membrane blebbing, chromatin condensation, DNA hydrolysis, and nuclear fragmentation. These dramatic structural and biochemical alterations result not only in the controlled dismantling of the cell, but also in the efficient recognition and removal of apoptotic cells by phagocytes. Necrosis, which is typically nonprogrammed or imposed upon the cell by overwhelming membrane or organelle damage, is characterized by rapid plasma membrane rupture followed by organelle and cell swelling. Necrosis is often provoked by infectious agents or a severe departure from physiological conditions. This unit describes protocols for the measurement of apoptosis and for distinguishing apoptosis from necrosis. PMID- 26836511 TI - Isolation of T Cells Using Rosetting Procedures. AB - This unit describes a procedure for separating T cells from other mononuclear cells by exploiting the unique ability of cells to bind to and form rosettes with sheep red blood cells (SRBC). This isolation method also allows recovery of the nonrosetting cell population (B lymphocytes, monocytes, and macrophages). Neuraminidase- and 2-aminoethylisothiouronium bromide (AET)-treated SRBC are used for rosetting because of enhanced binding to T cells. It should be noted that use of the rosetting technique to obtain purified T cells or purified non-T cells by negative selection has largely been superceded by other techniques such as panning and immunomagnetic beads. PMID- 26836510 TI - Culture, Expansion, and Differentiation of Murine Megakaryocytes from Fetal Liver, Bone Marrow, and Spleen. AB - Megakaryocytes (MKs) are the source of circulating platelets and are readily recognized by their large size and distinctive morphology. Their poor representation in hematopoietic tissues often requires considerable ex vivo expansion to generate cells for biochemical and cell biological studies. These experimental protocols describe the assessment of megakaryocytic potential within hematopoietic precursor cells in the bone marrow by colony-forming assays and expansion and enrichment of MKs from cultured fetal liver or spleen or bone marrow cells. Although these MKs are not synchronized in their maturation, they can be enriched over an albumin step gradient, and one-third to one-half of recovered cells will typically elaborate proplatelets, the immediate precursors of blood platelets. Both protocols require recombinant thrombopoietin (TPO) as a growth factor. Support protocols describe methods for preparing fetal liver cells, identifying mature rodent MKs by staining for acetylcholinesterase activity, and staining (May-Grunwald-Giemsa) mixed populations on cytocentrifuged blood cell preparations. PMID- 26836512 TI - Isolation of Human Basophils. AB - Isolating human basophils from blood has long been hampered by the fact that these granulocytes represent just 1% or less of the circulating leukocyte population. We describe herein laboratory protocols that have been refined over the past ~25 years that now enable investigators to prepare basophils for use in a variety of assays to assess the in vitro biology of these immune cells, both in IgE -dependent and -independent responses. PMID- 26836513 TI - Multivoxel Object Representations in Adult Human Visual Cortex Are Flexible: An Associative Learning Study. AB - Learning associations between co-occurring events enables us to extract structure from our environment. Medial-temporal lobe structures are critical for associative learning. However, the role of the ventral visual pathway (VVP) in associative learning is not clear. Do multivoxel object representations in the VVP reflect newly formed associations? We show that VVP multivoxel representations become more similar to each other after human participants learn arbitrary new associations between pairs of unrelated objects (faces, houses, cars, chairs). Participants were scanned before and after 15 days of associative learning. To evaluate how object representations changed, a classifier was trained on discriminating two nonassociated categories (e.g., faces/houses) and tested on discriminating their paired associates (e.g., cars/chairs). Because the associations were arbitrary and counterbalanced across participants, there was initially no particular reason for this cross-classification decision to tend toward either alternative. Nonetheless, after learning, cross-classification performance increased in the VVP (but not hippocampus), on average by 3.3%, with some voxels showing increases of up to 10%. For example, a chair multivoxel representation that initially resembled neither face nor house representations was, after learning, classified as more similar to that of faces for participants who associated chairs with faces and to that of houses for participants who associated chairs with houses. Additionally, learning produced long-lasting perceptual consequences. In a behavioral priming experiment performed several months later, the change in cross-classification performance was correlated with the degree of priming. Thus, VVP multivoxel representations are not static but become more similar to each other after associative learning. PMID- 26836514 TI - Dopamine Modulation of Intertemporal Decision-making: Evidence from Parkinson Disease. AB - Choosing between smaller prompt rewards and larger later rewards is a common choice problem, and studies widely agree that frontostriatal circuits heavily innervated by dopamine are centrally involved. Understanding how dopamine modulates intertemporal choice has important implications for neurobiological models and for understanding the mechanisms underlying maladaptive decision making. However, the specific role of dopamine in intertemporal decisions is not well understood. Dopamine may play a role in multiple aspects of intertemporal choices--the valuation of choice outcomes and sensitivity to reward delays. To assess the role of dopamine in intertemporal decisions, we tested Parkinson disease patients who suffer from dopamine depletion in the striatum, in either high (on medication, PDON) or low (off medication, PDOFF) dopaminergic states. Compared with both PDOFF and healthy controls, PDON made more farsighted choices and reduced their valuations less as a function of increasing time to reward. Furthermore, reduced discounting in the high dopaminergic state was robust across multiple measures, providing new evidence for dopamine's role in making decisions about the future. PMID- 26836516 TI - Upper Beta Band Oscillations in Human Premotor Cortex Encode Subjective Choices in a Vibrotactile Comparison Task. AB - Comparisons of sequentially presented vibrotactile frequencies have been extensively studied using electrophysiological recordings in nonhuman primates. Although neural signatures for working memory aspects of such tasks were recently also identified in human oscillatory EEG activity, homologue correlates of the comparison process are yet unknown. Here, we recorded EEG activity while participants decided which of two sequentially presented vibrotactile stimuli had a higher frequency. Because choices in this type of task are known to be systematically biased by the time-order effect, we applied Bayesian modeling to account for individual choice behavior. Using model-based EEG analysis, we found that upper beta band amplitude (~20-30 Hz) was modulated by participants' choices. The modulation emerged ~750 msec before a behavioral response was given and was source-localized to premotor areas.Importantly, the choice-dependent modulation of beta band amplitude was invariant to different motor response mappings and reflected the categorical outcome of the subjective comparison between the two frequencies. Consistently, this pattern was evident for both correct and incorrect trials, indicating that the beta band amplitude mirrors the internal representation of the comparison outcome. Our data complement previous findings in nonhuman primates and corroborate that the beta band activity in premotor areas reflects the categorical outcome of a sensory comparison prior to translation into an effector-specific motor command. PMID- 26836517 TI - Effects of Awareness on the Control of Attention. AB - Previous studies show that it is possible to attend to a stimulus without awareness of it. Whether attention and awareness are independent or have a specific relationship, however, remains debated. Here, we tested three aspects of visual attention with and without awareness of the visual stimulus. Metacontrast masking rendered participants either subjectively aware or not aware of the stimulus. Attention drawn to the stimulus was measured by using the stimulus as a cue in a spatial attention task. We found that attention was drawn to the stimulus regardless of whether or not people were aware of it. However, attention changed significantly in the absence of awareness in at least three ways. First, attention to a task-relevant stimulus was less stable over time. Second, inhibition of return, the automatic suppression of attention to a task-irrelevant stimulus, was reduced. Third, attention was more driven by the luminance contrast of the stimulus. These findings add to the growing information on the behavior of attention with and without awareness. The findings are also consistent with our recently proposed account of the relationship between attention and awareness. In the attention schema theory, awareness is the internal model of attention. Just as the brain contains a body schema that models the body and helps control the body, so it contains an attention schema that helps control attention. In that theory, in the absence of awareness, the control of attention should suffer in basic ways predictable from dynamical systems theory. The present results confirm some of those predictions. PMID- 26836515 TI - Dissociable Effects of Dopamine on the Initial Capture and the Reactive Inhibition of Impulsive Actions in Parkinson's Disease. AB - Dopamine plays a key role in a range of action control processes. Here, we investigate how dopamine depletion caused by Parkinson disease (PD) and how dopamine restoring medication modulate the expression and suppression of unintended action impulses. Fifty-five PD patients and 56 healthy controls (HCs) performed an action control task (Simon task). PD patients completed the task twice, once withdrawn from dopamine medications and once while taking their medications. PD patients experienced similar susceptibility to making fast errors in conflict trials as HCs, but PD patients were less proficient compared with HCs at suppressing incorrect responses. Administration of dopaminergic medications had no effect on impulsive error rates but significantly improved the proficiency of inhibitory control in PD patients. We found no evidence that dopamine precursors and agonists affected action control in PD differently. Additionally, there was no clear evidence that individual differences in baseline action control (off dopamine medications) differentially responded to dopamine medications (i.e., no evidence for an inverted U-shaped performance curve). Together, these results indicate that dopamine depletion and restoration therapies directly modulate the reactive inhibitory control processes engaged to suppress interference from the spontaneously activated response impulses but exert no effect on an individual's susceptibility to act on impulses. PMID- 26836520 TI - Application of lidar techniques to time-of-flight range imaging. AB - Amplitude-modulated continuous wave (AMCW) time-of-flight (ToF) range imaging cameras measure distance by illuminating the scene with amplitude-modulated light and measuring the phase difference between the transmitted and reflected modulation envelope. This method of optical range measurement suffers from errors caused by multiple propagation paths, motion, phase wrapping, and nonideal amplitude modulation. In this paper a ToF camera is modified to operate in modes analogous to continuous wave (CW) and stepped frequency continuous wave (SFCW) lidar. In CW operation the velocity of objects can be measured. CW measurement of velocity was linear with true velocity (R2=0.9969). Qualitative analysis of a complex scene confirms that range measured by SFCW is resilient to errors caused by multiple propagation paths, phase wrapping, and nonideal amplitude modulation which plague AMCW operation. In viewing a complicated scene through a translucent sheet, quantitative comparison of AMCW with SFCW demonstrated a reduction in the median error from -1.3 m to -0.06 m with interquartile range of error reduced from 4.0 m to 0.18 m. PMID- 26836519 TI - Lasing in imperfectly aligned cholesterics. AB - Optically pumped light emissions in imperfectly aligned dye-doped cholesteric cells with glance and frosted glass substrates of three different cell gap thicknesses are experimentally studied. Alignment imperfections show up in emission spectra by a broadening of the photonic bandgap (PhBG) lasing (allowed) lines at short- and long-wavelength PhBG edges and by an additional (forbidden) emission line inside the PhBG. Forbidden and allowed lines differ distinctively by their stability in the course of pumping. The origin of the forbidden line is discussed. PMID- 26836521 TI - Athermalization and thermal characteristics of multilayer diffractive optical elements. AB - A mathematical model to analyze the thermal characteristics of the multilayer diffractive optical elements (MLDOEs) is presented with consideration of the thermal characteristics for the refractive optical elements and single-layer diffractive optical elements. The analysis process of athermalization for MLDOEs by using the opto-thermal expansion coefficient of optical materials is given. Meanwhile, the microstructure heights of surface relief MLDOEs, the optical path difference, and the polychromatic integral diffraction efficiency with the ambient temperature changed are analyzed. The analysis results can be used to guide an athermalization design for the hybrid refractive-diffractive optical systems with MLDOEs. PMID- 26836518 TI - Reconciling the understanding of 'hydrophobicity' with physics-based models of proteins. AB - The idea that a 'hydrophobic energy' drives protein folding, aggregation, and binding by favoring the sequestration of bulky residues from water into the protein interior is widespread. The solvation free energies (DeltaGsolv) of small nonpolar solutes increase with surface area (A), and the free energies of creating macroscopic cavities in water increase linearly with A. These observations seem to imply that there is a hydrophobic component (DeltaGhyd) of DeltaGsolv that increases linearly with A, and this assumption is widely used in implicit solvent models. However, some explicit-solvent molecular dynamics studies appear to contradict these ideas. For example, one definition (DeltaG(LJ)) of DeltaGhyd is that it is the free energy of turning on the Lennard Jones (LJ) interactions between the solute and solvent. However, DeltaG(LJ) decreases with A for alanine and glycine peptides. Here we argue that these apparent contradictions can be reconciled by defining DeltaGhyd to be a near hard core insertion energy (DeltaGrep), as in the partitioning proposed by Weeks, Chandler, and Andersen. However, recent results have shown that DeltaGrep is not a simple function of geometric properties of the molecule, such as A and the molecular volume, and that the free energy of turning on the attractive part of the LJ potential cannot be computed from first-order perturbation theory for proteins. The theories that have been developed from these assumptions to predict DeltaGhyd are therefore inadequate for proteins. PMID- 26836522 TI - Monocular-binocular feature fidelity induced index for stereoscopic image quality assessment. AB - Perceptual three-dimensional image quality assessment (3D-IQA) aims to use computational models to measure image quality in a way that is consistent with human visual perception. Unlike previous studies that directly extended the two dimensional metrics to the three-dimensional (3D) case, the major technical innovation of this paper is to simulate monocular and binocular visual perception and propose a monocular-binocular feature fidelity induced index for 3D-IQA. To be more specific, in the training stage, we train monocular and binocular dictionaries from the training database, so that the latent response properties can be represented as a set of basis vectors. In the quality estimation stage, we compute monocular feature fidelity and binocular feature fidelity indexes based on the estimated sparse coefficient vectors and compute a global energy response similarity index by considering global energy changes. The final quality score is obtained by incorporating them. Experimental results on four 3D-IQA databases demonstrate that in comparison with the most relevant existing methods, the devised algorithm achieves high consistency alignment with subjective assessment. PMID- 26836523 TI - Study of spectral linewidth in Ne-like Se x-ray laser. AB - Based on the modeling of the geometrically dependent gain coefficient (GDGC) and rate equations, this theoretical study explains the spectral linewidth behavior in an Se x-ray laser operating at 206.4 A. The study used the reported experimental measurements for an Se target of 6.3 cm in length for the analysis. To obtain a finite value for the amplified spontaneous emission (ASE) intrinsic linewidth that initiates at the threshold length, we subtracted the ASE intensity background from the calculated ASE intensity to derive the corresponding FWHM. For homogeneously and Doppler broadened linewidths of 14 mA and 36 mA, we calculated the ASE Voigt profile linewidth to be 44 mA, initiated at the threshold length of 0.13 cm. The interaction is rather insensitive to the collision broadening; for the homogeneously broadened linewidth up to 21 mA, we could still explain the linewidth measurements. In this case, we calculated the related Voigt profile linewidth to be 48.5 mA. The current GDGC modeling approach greatly simplified the ASE analyses of these lasers. PMID- 26836524 TI - Using a laser source to measure the refractive index of glass beads and Debye theory analysis. AB - Using a monochromatic laser beam to illuminate a homogeneous glass bead, some rainbows will appear around it. This paper concentrates on the study of the scattering intensity distribution and the method of measuring the refractive index for glass beads based on the Debye theory. It is found that the first rainbow due to the scattering superposition of backward light of the low refractive-index glass beads can be explained approximately with the diffraction, the external reflection plus the one internal reflection, while the second rainbow of high-refractive-index glass beads is due to the contribution from the diffraction, the external reflection, the direct transmission, and the two internal reflections. The scattering intensity distribution is affected by the refractive index, the radius of the glass bead, and the incident beam width. The effects of the refractive index and the glass bead size on the first and second minimum deviation angle position are analyzed in this paper. The results of the measurements agree very well with the specifications. PMID- 26836526 TI - Z-scan studies of the nonlinear optical properties of gold nanoparticles prepared by electron beam deposition. AB - This paper details the fabrication process for placing single-layer gold (Au) nanoparticles on a planar substrate, and investigation of the resulting optical properties that can be exploited for nonlinear optics applications. Preparation of Au nanoparticles on the substrate involved electron beam deposition and subsequent thermal dewetting. The obtained thin films of Au had a variation in thicknesses related to the controllable deposition time during the electron beam deposition process. These samples were then subjected to thermal annealing at 600 degrees C to produce a randomly distributed layer of Au nanoparticles. Observation from field-effect scanning electron microscope (FESEM) images indicated the size of Au nanoparticles ranges from ~13 to ~48 nm. Details of the optical properties related to peak absorption of localized surface plasmon resonance (LSPR) of the nanoparticle were revealed by use of UV-Vis spectroscopy. The Z-scan technique was used to measure the nonlinear effects on the fabricated Au nanoparticle layers where it strongly relates LSPR and nonlinear optical properties. PMID- 26836525 TI - Rapid long-wave infrared laser-induced breakdown spectroscopy measurements using a mercury-cadmium-telluride linear array detection system. AB - In this work, we develop a mercury-cadmium-telluride linear array detection system that is capable of rapidly capturing (~1-5 s) a broad spectrum of atomic and molecular laser-induced breakdown spectroscopy (LIBS) emissions in the long wave infrared (LWIR) region (~5.6-10 MUm). Similar to the conventional UV-Vis LIBS, a broadband emission spectrum of condensed phase samples covering the whole 5.6-10 MUm region can be acquired from just a single laser-induced microplasma or averaging a few single laser-induced microplasmas. Atomic and molecular signature emission spectra of solid inorganic and organic tablets and thin liquid films deposited on a rough asphalt surface are observed. This setup is capable of rapidly probing samples "as is" without the need of elaborate sample preparation and also offers the possibility of a simultaneous UV-Vis and LWIR LIBS measurement. PMID- 26836527 TI - Two-stage solar concentrators based on parabolic troughs: asymmetric versus symmetric designs. AB - While nonimaging concentrators can approach the thermodynamic limit of concentration, they generally suffer from poor compactness when designed for small acceptance angles, e.g., to capture direct solar irradiation. Symmetric two stage systems utilizing an image-forming primary parabolic concentrator in tandem with a nonimaging secondary concentrator partially overcome this compactness problem, but their achievable concentration ratio is ultimately limited by the central obstruction caused by the secondary. Significant improvements can be realized by two-stage systems having asymmetric cross-sections, particularly for 2D line-focus trough designs. We therefore present a detailed analysis of two stage line-focus asymmetric concentrators for flat receiver geometries and compare them to their symmetric counterparts. Exemplary designs are examined in terms of the key optical performance metrics, namely, geometric concentration ratio, acceptance angle, concentration-acceptance product, aspect ratio, active area fraction, and average number of reflections. Notably, we show that asymmetric designs can achieve significantly higher overall concentrations and are always more compact than symmetric systems designed for the same concentration ratio. Using this analysis as a basis, we develop novel asymmetric designs, including two-wing and nested configurations, which surpass the optical performance of two-mirror aplanats and are comparable with the best reported 2D simultaneous multiple surface designs for both hollow and dielectric-filled secondaries. PMID- 26836528 TI - Quantum efficiency of InSbBi quantum dot photodetector. AB - An InSb(1-x)Bi(x) quantum dot (QD) photodetector was studied in this work. First, the quantum efficiency (QE) was modeled for this structure where the relations of electron and hole densities and their contribution to current density are derived. The absorption of p-, n- and depletion regions were calculated before specifying their contribution to QE. It is shown that adding Bi to Sb-based QD structures increases their absorption and QE. High Bi content extended the cutoff detection wavelength of these detectors. PMID- 26836529 TI - Noise reducing phase retrieval. AB - In the context of imaging using the Hanbury Brown-Twiss effect, this paper describes a phase retrieval algorithm capable of producing high-quality images despite large amounts of noise in the coherence magnitude measurement data. Previously the problem was conceived as two distinct steps: coherence magnitude estimation, followed by image construction. The present unified formulation accepts highly noisy data and estimates both the measurement noise and the image using the numerous constraints on the coherence data, the image, and their interrelations. The technique is shown to reduce the necessary imaging time by many orders of magnitude. PMID- 26836530 TI - Correction of rolling wheel images captured by a linear array camera. AB - As a critical part of the train, wheels affect railway transport security to a large extent. This paper introduces an online method to detect the wheel tread of a train. The wheel tread images are collected by industrial linear array charge coupled device (CCD) cameras when the train is moving at a low velocity. This study defines the positioning of the cameras and determines how to select other parameters such as the horizontal angle and the scanning range. The deformation of the wheel tread image can be calculated based on these parameters and corrected by gray interpolation. PMID- 26836531 TI - Compact photonic crystal circulator with flat-top transmission band created by cascading magneto-optical resonance cavities. AB - A new type of compact three-port circulator with flat-top transmission band (FTTB) in a two-dimensional photonic crystal has been proposed, through coupling the cascaded magneto-optical resonance cavities to waveguides. The coupled-mode theory is applied to investigate the coupled structure and analyze the condition to achieve FTTB. According to the theoretical analysis, the structure is further optimized to ensure that the condition for achieving FTTB can be satisfied for both cavity-cavity coupling and cavity-waveguide coupling. Through the finite element method, it is demonstrated that the design can realize a high quality, nonreciprocal circulating propagation of waves with an insertion loss of 0.023 dB and an isolation of 23.3 dB, covering a wide range of operation frequency. Such a wideband circulator has potential applications in large-scale integrated photonic circuits for guiding or isolating harmful optical reflections from load elements. PMID- 26836532 TI - Shape from focus for large image fields. AB - Shape from focus is a method for the accurate measurement of the geometrical shape of objects. The measurement principle is the local focus search. The method is suitable only for objects with a texture (optically rough surface). The longitudinal coordinate of a surface point is determined from the maximum of the focus measure function. The focus measure function expresses the quality of focus in a small image area. The measurement is fast because the focus measure function shows no oscillations. Thus, a large sampling step can be used. We present experimental results that demonstrate the capability of the proposed method. PMID- 26836533 TI - Monostatic all-fiber scanning LADAR system. AB - A compact scanning LADAR system based on a fiber-coupled, monostatic configuration which transmits (TX) and receives (RX) through the same aperture has been developed. A small piezo-electric stripe actuator was used to resonantly vibrate a fiber cantilever tip and scan the transmitted near-single-mode optical beam and the cladding mode receiving aperture. When compared to conventional bi static systems with polygon, galvo, or Risley-prism beam scanners, the described system offers several advantages: the inherent alignment of the receiver field-of view (FOV) relative to the TX beam angle, small size and weight, and power efficiency. Optical alignment of the system was maintained at all ranges since there is no parallax between the TX beam and the receiver FOV. A position-sensing detector (PSD) was used to sense the instantaneous fiber tip position. The Si PSD operated in a two-photon absorption mode to detect the transmitted 1.5 MUm pulses. The prototype system collected 50,000 points per second with a 6 degrees full scan angle and a 27 mm clear aperture/40 mm focal length TX/RX lens, had a range precision of 4.7 mm, and was operated at a maximum range of 26 m. PMID- 26836534 TI - Design of superachromatic quarter-wave retarders in a broad spectral range. AB - A superachromatic quarter-wave retarder using an arbitrary number of waveplates in a broadband spectral range has been proposed. Their design is based on the optimization of a merit function, the achromatism degree (AcD), which represents a global behavior metric for the retardation. By means of this technique, the thickness and azimuth of each waveplate is determined. The achromatism degree is a measure of the distance between the overall retardation and a target retardation weighted by the spectrum of the incident light. We report on a particular case where all waveplates are made of quartz. As application examples, the design of a quarter-wave retarder using two, three, and four waveplates in the spectral ranges of 500-700 nm and 400-1000 nm was studied. The numerical results show that for these ranges, the best designs obtained present a maximum difference of 0.013 degrees and 0.010 degrees with respect to the target retardation, respectively. In addition, an analysis of their achromatic stability is presented. These results can be applied in the aerospace industry, spectroscopic ellipsometry, and spectrogoniometry, among others. PMID- 26836535 TI - Control of the differential interference contrast in reinjected bimode laser. AB - We have demonstrated, both theoretically and experimentally, that it is possible to control (i.e., to enhance or cancel) the contrast of the interference pattern appearing in the intensity images obtained with a laser optical feedback imaging (LOFI) setup using a bimode laser. The laser is composed of two coupled orthogonally polarized states that interact (i.e., interfere) through the cross saturation laser dynamics. We created the contrast control by choosing the frequency shift (i.e., the beating frequency) between the feedback electric fields and the intracavity electric fields. We have shown that the interference contrast of the output power modulation of the laser total intensity is independent from the frequency shift and is always maximal. On the other hand, the interference contrast of each polarization state is frequency dependent. We obtained the maximal contrast when the frequency shift was equal to one of the resonance frequencies of the bimode dynamics, and was very low (and almost cancels) for an intermediate frequency located at the intersection of the two resonance curves. PMID- 26836536 TI - Development of a compact multipass oxygen sensor used for gas diffusion studies in opaque media. AB - A highly scattering porous ceramic sample is employed as a miniature random scattering multipass gas cell for monitoring of oxygen content in opaque media, that is, wood materials in the present work. Gas in scattering media absorption spectroscopy is used by employing a 760 nm near-infrared laser diode to probe the absorption of molecular oxygen enclosed in the pores of the ceramic material working as the multipass gas cell, with a porosity of 75%. A path length enhancement of approximately 26 times and a signal-to-noise ratio of about 60 were obtained for the ceramic sample used in this work. The gas sensor was then used in a case study of the gas diffusion in wood materials, namely, oak, spruce, and mahogany samples. Differences depending on whether gas diffusion was studied longitudinal or radial to the tree annual rings are demonstrated, with very little gas diffusing in the radial direction. We can also observe that the gas diffusion for the densest material-oak-had the fastest diffusion time, and mahogany, which had the lowest density, showed the slowest diffusion time. PMID- 26836537 TI - Differential method for processing scanning lidar data. AB - The significant deficiency of the classic multiangle data-processing technique is that the accuracy of the lidar-data inversion strongly depends on whether the assumption of the horizontal stratification of the searched atmosphere is valid. The aggravating factor is that no reliable methodology exists that would allow establishment of whether the above assumption is met; even the thorough analysis of the measured lidar signals rarely allows for a reliable conclusion about the fulfillment of this requirement. In this study, a new multiangle differential data-processing method is considered, which provides the renewed interpretation of multiangle measurements. It allows for distinguishing and separating the data points from the areas where the backscatter extinction coefficient is not constant in the horizontal directions. Simulated and experimental data are presented that illustrate the principle and specifics of such a differential technique. PMID- 26836538 TI - Experimental demonstration of polarization smoothing in a convergent beam. AB - We report an experimental demonstration of polarization smoothing by using a specially cut KDP plate in the convergent ultraviolet (351 nm wavelength) section of a high-power laser system. A 410 mm*410 mm*10 mm sized KDP plate placed after the final focus lens successfully reduced the focal spot intensity contrast to 75.6%, which is in good agreement with the theoretical expectation. In our experiment, no obvious transverse stimulated scattering was observed with the maximum 351 nm laser energy of 4032 J/3 ns, thus indicating the operation safety margin of our laser system. PMID- 26836539 TI - Microscale hemisphere patterned backside mirror for GaN-based light-emitting diodes. AB - Three-dimensional backside mirrors patterned by microscale hemispheres were proposed to enhance the light extraction efficiency (LEE) of light-emitting diode (LED) chips. In a thorough investigation, various design parameters, including duty ratio, pattern materials, concave/convex pattern style, aspect ratio, types of mirrors, and chip configurations, were studied using the Monte Carlo ray tracing method. The square lattice of hemispheres with various radius and lattice constants was designed. It is shown that the close-packed hemisphere pattern is preferred. Several materials, including SiO2, polystyrene, sapphire, ZnO, GaN, and TiO2, were selected for the pattern layer. Generally, the optimized pattern material is the substrate material. Comparing the LEE induced by a concave pattern and a convex pattern, it is shown that the former benefits a higher LEE. Various aspect ratios of the spherical caps were also discussed. As the height of the cap increases, the LEE increases or decreases for a concave pattern or a convex pattern, respectively. Considering various mirrors, it is shown that the LEE increases with the increasing of the integral reflectivity of backside mirrors. Finally, the optimized structure parameters for backside mirrors were used in different chip configurations. In the case that of all lights extracted from LED chips were calculated, the LEE can be enhanced by 52%, 135%, and 173% for conventional, flip-chip, and thin-film LED chips, respectively. If only the lights that escaped from the top surface were calculated, the LEE can be enhanced by 65%, 209%, and 263% for conventional, flip-chip, and thin-film LED chips, respectively. PMID- 26836540 TI - Effect of incorporation of different modified Al2O3 nanoparticles on holographic characteristics of PVA/AA photopolymer composites. AB - Al2O3 nanoparticles modified with different chemical reagents, prepared by using three chemical dispersants [high definition (HD), sodium dodecyl benzene sulfonate, and cetyl trimethyl ammonium chloride], were doped into photopolymer films in a polyvinyl alcohol/acrylamide (PVA/AA) system, respectively. A 647 nm Ar-Kr laser was used to expose and study the holographic properties of the samples. The research shows that doping Al2O3 nanoparticles into PVA/AA photopolymer film leads to different levels of improvement of the holographic characteristics. The diffraction efficiency of the sample can be raised to 93.8%, the maximum refractive index modulation increased to 2.28*10(-3), the shrinkage can be depressed to 0.8%, and the Bragg mismatch is 0.04 degrees , while the concentration of 10 nm Al2O3 nanoparticles modified by HD dispersant is 1.02*10( 3) mol.L(-1). PMID- 26836541 TI - Simultaneous phase-shifting interferometry: immune to azimuth error of fast-axes in retarder array. AB - Simultaneous phase-shifting interferometry based on a 2*2 retarder array with random fast-axes (RARF-SPSI) is proposed for real-time wavefront measurements. The retarder array is used as the phase-shift component, where the phase retardances are pi/2, pi, 3pi/2, and 2pi and the four fast-axes of the four retarders can be somewhat random. In this paper, the mathematical model of RARF SPSI is built by using a Stokes vector and a Mueller matrix, the phase demodulation method through solving equations is derived, and the coefficient matrix of the equations that is associated with the azimuth of the fast-axes is calculated by Fourier analysis. Then the corresponding simulation analysis is executed. In the experiment, four simultaneous phase-shifting interferograms are captured and the phase distribution under test is demodulated through the proposed method. Compared with the four-bucket phase-shifting algorithm adopted in traditional simultaneous phase-shifting interferometry, the ripple error is suppressed well. The advantage of the proposed RARF-SPSI is that there is no need to calibrate the fast-axes of the phase-shift component before measuring; in other words, the phase demodulation error caused by the azimuth error of fast axes is eliminated. PMID- 26836542 TI - Guide filter-based gradient vector flow module for infrared image segmentation. AB - Infrared image segmentation is a challenging topic since infrared images are characterized by high noise, low contrast, and weak edges. Active contour models, especially gradient vector flow (GVF), have better segmentation performance for clear images. However, the GVF model has the drawbacks of sensitivity to noise and adaptability of the parameters, decreasing the effect of infrared image segmentation significantly. To address these problems, this paper proposes a guide filter-based gradient vector flow module for infrared image segmentation (GFGVF). First, a guide filter is exploited to construct a novel edge map, providing characteristics of the image edge while excluding the effects of noise. This alleviates the possibility of edge leakage caused by using the traditional edge map. Then, a novel weighting function is constructed to effectively handle the extended capture range and preserving the edge even with noise existing. The experimental results demonstrate that the GFGVF model possesses good properties such as large capture range, concavity convergence, noise robustness, and alleviative boundary leakage. PMID- 26836543 TI - Spatial-spectral characterization of focused spatially chirped broadband laser beams. AB - Proper alignment is critical to obtain the desired performance from focused spatially chirped beams, for example in simultaneous spatial and temporal focusing (SSTF). We present a simple technique for inspecting the beam paths and focusing conditions for the spectral components of a broadband beam. We spectrally resolve the light transmitted past a knife edge as it was scanned across the beam at several axial positions. The measurement yields information about spot size, M2, and the propagation paths of different frequency components. We also present calculations to illustrate the effects of defocus aberration on SSTF beams. PMID- 26836544 TI - Surface defect detection method for glass substrate using improved Otsu segmentation. AB - The image quality degradation caused by noise makes the automatic optical inspection of surface defects difficult. This paper develops a method based on thresholding segmentation to detect the surface defects in a glass substrate. Traditional Otsu segmentation has poor anti-noise ability. In order to improve the traditional Otsu method, a straight-line intercept histogram is established directly from the two-dimensional information of an image, and then Otsu criteria can be used to find the best intercept threshold from the one-dimensional histogram established. The improved Otsu algorithm not only is simpler than the two-dimensional Otsu methods, but also has a robust anti-noise ability. In the surface defect detection, the contrast feature between object and background is simply extracted after the segmentation based on the improved Otsu method, and surface defects can be decided by the threshold of the contrast feature. The data used in the experiments include the surface images acquired by a line-scan CCD camera. The experimental results demonstrate that the proposed method is effective and computationally efficient. PMID- 26836545 TI - Structure optimization of small-diameter polarization-maintaining photonic crystal fiber for mini coil of spaceborne miniature fiber-optic gyroscope. AB - A small-diameter polarization-maintaining photonic crystal fiber (PM-PCF) for mini coils of spaceborne miniature fiber-optic gyroscopes is proposed in this paper. To ensure the strength of the small-diameter PM-PCF, a four-ring air holes structure is adopted. Using the full vector finite element method, dependence studies of modal field distribution, birefringence, and confinement loss on several key structure parameters are numerically investigated. The optimized parameter region is obtained. An optimized PM-PCF is fabricated, which can achieve similar to or even better optical properties than that of commercial PM PCFs. The coating and cladding diameters of the optimized PM-PCF are 135 MUm and 100 MUm, respectively. Meanwhile, the optimized small-diameter PM-PCF shows a proof test level of 0.5%. The attenuation of the PM-PCF at 1550 nm is ~2 dB/km. Typical volume of a mini coil wound with 300 m optimized PM-PCF is 5.9 cm3, which is decreased by ~60% compared with a commercial PM-PCF coil of the same length. The bias stability of this coil is comparable with that of a conventional PMF coil of comparable length. Thus, the optimized small-diameter PM-PCF is suitable for mini coils of spaceborne miniature fiber-optic gyroscopes. PMID- 26836546 TI - Measurement of displacement and distance with a polarization phase shifting folded Twyman Green interferometer. AB - A Sagnac interferometer (SI), consisting of a polarization beam splitter (PBS), along with two equally spaced plane mirrors that are inclined at 45 degrees to each other, is transformed into a folded Twyman Green interferometer (TGI) by placing a mirrored parallel plate (MPP) into the hypotenuse arm of the SI. The converging input beam produced by a telescope objective (TO) is split into reflected (s-polarized) and transmitted (p-polarized) components by the PBS. The p- and s-polarized focal spots are made to fall on the mirrored end surfaces of the parallel plate (PP). The retroreflected p- and s-polarized beams become collimated after passing through the TO. A linear shift of the PP in either (longitudinal) direction alters the positions of the p- and s-polarized focal spots and results in a set of converging and diverging spherical wavefronts that interfere to form concentric circular fringes. We applied polarization phase shifting interferometry to obtain the optical path difference (OPD) variation of the interference field. The displacement is calculated from the OPD variation. A validation experiment has been carried out by introducing known shifts to the PP. The setup can be used for displacement as well as distance measurement. PMID- 26836547 TI - Fiber dispersion measurement using chirped laser dispersion spectroscopy technique. AB - Utilizing the fundamentals of chirped laser dispersion spectroscopy, an alternative method of fiber dispersion measurement is presented. The dispersion of the device under test is probed through the interaction of copropagating electromagnetic waves and subsequent heterodyne detection and frequency demodulation. Measurement of the dispersion parameter, D, is possible with this direct measurement scheme. PMID- 26836548 TI - Analysis and quantification of collagen organization with the structure tensor in second harmonic microscopy images of ocular tissues. AB - The important biological role of collagen-based tissues and the changes produced in the fiber distribution under particular situations (surgery, pathology, external damage, etc.) require tools for the analysis of the collagen organization that might potentially help in early diagnoses. Since collagen structures provide efficient second harmonic generation (SHG) signals, SHG microscopy has emerged as a powerful technique to visualize collagen fibers and qualitatively discriminate normal from abnormal tissues. Here we propose a quantitative method based on the structure tensor to quantify the different organization of collagen patterns in SHG images of ocular tissues. Results show that well-organized collagen distributions present a high degree of isotropy (DoI), a dominant orientation (PO), and a low structural dispersion (SD). On the other hand, the PO vanishes when the collagen tissue is not organized as a consequence of an increase in the SD and a decrease in the DoI. The proposed method is also able to discriminate partially organized samples. The combination of SHG microscopy and the structure tensor is a useful method to objectively classify collagen distributions. Clinical applications of this technique could help in the diagnosis and tracking of pathologies related to collagen disorders in connective tissue. PMID- 26836549 TI - Modular pump geometry for diode side-pumped high-power Nd:YAG rod laser. AB - In this paper, we present a modular design configuration to side-pump an Nd:YAG rod of a diode-pumped high-power CW laser. Independent modules in the form of discs are loaded with three-diode linear bar arrays at 120 degrees with respect to each other and are assembled along the length of the rod. By keeping successive discs at three different angular separations (the minimum, intermediate, and maximum), helical, 60 degrees rotated, and linear geometries, respectively, were created. Parameters like thermal lensing, fluorescence profile, laser beam profile, and beam quality factor (M2) were studied to compare the performances of different geometries. The results indicate that the 60 degrees rotated configuration provides the best performance when compared with rest of the schemes. To the best of our knowledge, this is the first time that such novel modular-type pump geometries with a provision for the angular separation of pump diodes have been tried. PMID- 26836550 TI - Investigation of the spectral reflectance and bidirectional reflectance distribution function of sea foam layer by the Monte Carlo method. AB - Spectral properties of sea foam greatly affect ocean color remote sensing and aerosol optical thickness retrieval from satellite observation. This paper presents a combined Mie theory and Monte Carlo method to investigate visible and near-infrared spectral reflectance and bidirectional reflectance distribution function (BRDF) of sea foam layers. A three-layer model of the sea foam is developed in which each layer is composed of large air bubbles coated with pure water. A pseudo-continuous model and Mie theory for coated spheres is used to determine the effective radiative properties of sea foam. The one-dimensional Cox Munk surface roughness model is used to calculate the slope density functions of the wind-blown ocean surface. A Monte Carlo method is used to solve the radiative transfer equation. Effects of foam layer thickness, bubble size, wind speed, solar zenith angle, and wavelength on the spectral reflectance and BRDF are investigated. Comparisons between previous theoretical results and experimental data demonstrate the feasibility of our proposed method. Sea foam can significantly increase the spectral reflectance and BRDF of the sea surface. The absorption coefficient of seawater near the surface is not the only parameter that influences the spectral reflectance. Meanwhile, the effects of bubble size, foam layer thickness, and solar zenith angle also cannot be obviously neglected. PMID- 26836551 TI - Coded aperture design in mismatched compressive spectral imaging. AB - Compressive spectral imaging (CSI) senses a scene by using two-dimensional coded projections such that the number of measurements is far less than that used in spectral scanning-type instruments. An architecture that efficiently implements CSI is the coded aperture snapshot spectral imager (CASSI). A physical limitation of the CASSI is the system resolution, which is determined by the lowest resolution element used in the detector and the coded aperture. Although the final resolution of the system is usually given by the detector, in the CASSI, for instance, the use of a low resolution coded aperture implemented using a digital micromirror device (DMD), which induces the grouping of pixels in superpixels in the detector, is decisive to the final resolution. The mismatch occurs by the differences in the pitch size of the DMD mirrors and focal plane array (FPA) pixels. A traditional solution to this mismatch consists of grouping several pixels in square features, which subutilizes the DMD and the detector resolution and, therefore, reduces the spatial and spectral resolution of the reconstructed spectral images. This paper presents a model for CASSI which admits the mismatch and permits exploiting the maximum resolution of the coding element and the FPA sensor. A super-resolution algorithm and a synthetic coded aperture are developed in order to solve the mismatch. The mathematical models are verified using a real implementation of CASSI. The results of the experiments show a significant gain in spatial and spectral imaging quality over the traditional grouping pixel technique. PMID- 26836552 TI - Analysis of heterodyne detection in the frequency domain. AB - As opposed to previous works, our research on heterodyne detection is performed in the frequency domain. Based on the planar wave, it is pointed out that the current amplitude of a heterodyne signal is proportional to the spectrum value of the quantum efficiency function of a detector, and the frequency corresponding to the value is decided by the beam's incident angle. The spectrum of the quantum efficiency function has a low-pass characteristic, and its cut-off frequency is determined by the diameter of the photosensitive surface. Consequently, the strength of the heterodyne signal current depends on the position of a specific frequency in the passband. Our study method is extended to the arbitrary wave and proven to be still effective. According to our analyses, it is concluded that, in addition to the energy decline of interference field, the main cause of performance deterioration resulting from various influential factors can be generally explained as a spectrum mismatch between the interference field and the quantum efficiency function. Based on the Gaussian wave mode, the fact is illustrated by making theoretical deductions, in which the effects of the misaligned angle and beams' spot position offset are treated as examples. Our work provides the possibility of introducing frequency-domain theories into further studies on heterodyne detection. PMID- 26836553 TI - Complex index of refraction estimation from degree of polarization with diffuse scattering consideration. AB - The estimation of the refractive index from optical scattering off a target's surface is an important task for remote sensing applications. Optical polarimetry is an approach that shows promise for refractive index estimation. However, this estimation often relies on polarimetric models that are limited to specular targets involving single surface scattering. Here, an analytic model is developed for the degree of polarization (DOP) associated with reflection from a rough surface that includes the effect of diffuse scattering. A multiplicative factor is derived to account for the diffuse component and evaluation of the model indicates that diffuse scattering can significantly affect the DOP values. The scattering model is used in a new approach for refractive index estimation from a series of DOP values that involves jointly estimating n, k, and rho(d)with a nonlinear equation solver. The approach is shown to work well with simulation data and additive noise. When applied to laboratory-measured DOP values, the approach produces significantly improved index estimation results relative to reference values. PMID- 26836554 TI - Phase shifting and phase retrieval with a fully automated laser diode system. AB - A low-cost and fully automated process for phase-shifting interferometry (PSI) by continuously changing the input voltage of a laser diode (LD) under the scheme of an unbalanced Twyman-Green interferometer (TGI) setup is presented. The input signal of a LD is controlled by a data acquisition (NI-DAQ) device that allows it to change its wavelength according to its tunability features. The automation and data analysis will be done using LabVIEW in combination with MATLAB. The phase map is obtained using the Carre algorithm. Measurements of visibility and phase shift to verify the PSI requirements are shown. It is demonstrated with experimental results and statistical analysis that the phase retrieval can be successfully achieved without calibration and using minimal optical devices. PMID- 26836555 TI - Passively Q-switched Nd:YAG ceramic laser with V(3+):YAG saturable absorber at 1357 nm. AB - 1357 nm single-wavelength continuous-wave and passively V(3+):YAGQ-switched Nd:YAG ceramic crystal lasers have been experimentally demonstrated for the first time to our knowledge. The output power of the continuous-wave laser was as high as 2.4 W under the incident pump power of 14.8 W. The corresponding optical to optical efficiency was about 16.2% and the slope efficiency was about 18.6%. The Q-switched laser remained single-wavelength output with a maximum average output power of 628 mW at the incident pump power of 12.4 W. The corresponding pulse width was 21 ns and the repetition frequency was 15 kHz. PMID- 26836556 TI - Comparison of online and offline tests in LED accelerated reliability tests under temperature stress. AB - Accelerated aging tests are the main method used in the evaluation of LED reliability, and can be performed in either online or offline modes. The goal of this study is to provide the difference between the two test modes. In the experiments, the sample is attached to different heat sinks to acquire the optical parameters under different junction temperatures of LEDs. By measuring the junction temperature in the aging process (Tj1), and the junction temperature in the testing process (Tj2), we achieve consistency with an online test of Tj1 and Tj2 and a difference with an offline test of Tj1 and Tj2. Experimental results show that the degradation rate of the luminous flux rises as Tj2 increases, which yields a difference of projected life L(70%) of 8% to 13%. For color shifts over 5000 h of aging, the online test shows a larger variation of the distance from the Planckian locus, about 40% to 50% more than the normal test at an ambient temperature of 25 degrees C. PMID- 26836557 TI - Temperature dependence of electro-optic effect and natural linear birefringence in quartz measured by low-coherence interferometry. AB - Temperature dependencies of the half-wave voltage and natural linear birefringence in mechanically free quartz are measured at 1560 nm in the temperature range of 85-310 K. Measurements are carried out using a low-coherence interferometric scheme with a pair of identical quartz crystals independently linked with a scanning Michelson interferometer. Half-wave voltage V11 driven by an electro-optic coefficient r11 grows from 868 kV at 85 K to 923 kV at 310 K. The temperature derivative of natural linear birefringence Deltan has nearly linear temperature dependence: ?Deltan/?T=-7.260*10(-7)-9.93*10(-10) T K(-1). Moderate temperature dependence of the electro-optic effect, along with other properties, makes quartz an appropriate sensing medium for electro-optic voltage sensors for the electric power industry. PMID- 26836558 TI - Improved multiple-wavelength Brillouin-Raman fiber laser assisted by four-wave mixing with a micro-air cavity. AB - In this paper, a multiple-wavelength Brillouin-Raman fiber laser (MBRFL) with enhanced performance is presented. This is attributed to the improved Fresnel reflection, thus strengthening four-wave mixing in the fiber laser cavity due to the insertion of a micro-air cavity. As a result, compared with the conventional MBRFL without a micro-air cavity, the thresholds of Brillouin Stokes (BS) lines are observed to be reduced, and more BS lines can be generated. In the experiment, a MBRFL having 40 BS lines is achieved with good stability on laser wavelengths and output power. In view of the fact that more BS lines can be established with a simple scheme and low pump power, our MBRFL promises to be employed as a multiwavelength source for optical communication. PMID- 26836559 TI - Structural and optical properties of erbium-doped willemite-based glass-ceramics. AB - Willemite-based glass-ceramic was prepared from waste material using a conventional melt and quenching method. The crystalline willemite-based glass ceramic was doped with Er2O3 (1-5 wt.%) followed by sintering at different temperatures (500 degrees C-1100 degrees C). Density and linear shrinkage were increased with the increase of the sintering temperature. Ultraviolet-visible spectroscopy (UV-Vis) confirmed an optimum optical absorption for sample doped with 3 wt.% of Er2O3 and sintered at 900 degrees C. Photoluminescence measurements further confirmed 3 wt.% of Er2O3 as the optimum percentage of dopant. Results suggested that the obtained glass-ceramic could be a promising material for use as fiber amplifiers. PMID- 26836560 TI - Self-referenced interferometer for cylindrical surfaces. AB - We present a new interferometric method for shape measurement of hollow cylindrical tubes. We propose a simple and robust self-referenced interferometer where the reference and object waves are represented by the central and peripheral parts, respectively, of the conical wave generated by a single axicon lens. The interferogram detected by a digital camera is characterized by a closed fringe pattern with a circular carrier. The interference phase is demodulated using spatial synchronous detection. The capabilities of the interferometer are experimentally tested for various hollow cylindrical tubes with lengths up to 600 mm. PMID- 26836561 TI - Investigation of phase effects of coherent beam combining for large-aperture ultrashort ultrahigh intensity laser systems. AB - Large-aperture ultrashort ultrahigh intensity laser systems are able to achieve unprecedented super-high peak power. However, output power from a single laser channel is not high enough for some important applications and it is difficult to improve output power from a single laser channel significantly in the near future. Coherent beam combining is a promising method which combines many laser channels to obtain much higher peak power than a single channel. In this work, phase effects of coherent beam combining for large-aperture ultrashort laser systems are investigated theoretically. A series of numerical simulations are presented to obtain the requirements of spatial phase for specific goals and the changing trends of requirements for different pulse durations and number of channels. The influence of wavefront distortion on coherent beam combining is also discussed. Some advice is proposed for improving the performance of combining. In total, this work could help to design a practical large-aperture ultrashort ultrahigh intensity laser system in the future. PMID- 26836562 TI - Characterization of polarizer made of the deep-UV birefringent crystal Ba2Mg(B3O6)2. AB - In optical communications and the laser industry, modulating the polarization of light requires crystals with both large birefringence and a wide transparent range. A good candidate for a deep-UV birefringent crystal is Ba2Mg(B3O6) because it has a large birefringence and short UV cutoff edge. We grew Ba2Mg(B3O6)2 crystals with sizes up to 41 mm*40 mm*7 mm using the top-seeded solution growth method. We obtained the thermal-expansion coefficients in different directions and the thermo-optic coefficients and then designed and manufactured a Glan-Taylor type polarizer to fulfill the commercial requirements. PMID- 26836563 TI - 5.7 W cw single-frequency laser at 671 nm by single-pass second harmonic generation of a 17.2 W injection-locked 1342 nm Nd : YVO4 ring laser using periodically poled MgO : LiNbO3. AB - We demonstrate a continuous wave single-frequency laser at 671.1 nm based on a high-power 888 nm pumped Nd:YVO4 ring laser at 1342.2 nm. Unidirectional operation of the fundamental ring laser is achieved with the injection-locking technique. A Nd:YVO4 microchip laser serves as the injecting seed source, providing a tunable single-frequency power of up to 40 mW. The ring laser emits a single-frequency power of 17.2 W with a Gaussian beam profile and a beam propagation factor of M2<1.1. A 60-mm-long periodically poled MgO-doped LiNbO3 crystal is used to generate the second harmonic in a single-pass scheme. Up to 5.7 W at 671.1 nm with a Gaussian shaped beam profile and a beam propagation factor of M2<1.2 are obtained, which is approximately twice the power of previously reported lasers. This work opens possibilities in cold atoms experiments with lithium, allowing the use of larger ensembles in magneto-optical traps or higher diffraction orders in atomic beam interferometers. PMID- 26836564 TI - Constraints on additivity of the 1D discrete linear canonical transform. AB - The continuous linear canonical transform (LCT) can describe a wide variety of paraxial (quadratic phase) first-order optical systems. Digital algorithms to numerically calculate the LCT are therefore important in modeling the field propagations and are also of interest for many digital signal-processing applications. The continuous LCT is additive (and unitary), but discretization can destroy additivity. In this paper, the general constraint sufficient to ensure the discrete LCTs are additive is derived. Often, we wish to decompose the transform into a series of more computationally efficient steps. Having previously discussed the unitarity of such algorithms, in this paper we consider how our additivity constraint applies to the direct method (DM) and spectral method (SM) algorithms. Examples are presented showing how to correct nonadditive calculations and to appropriately choose parameters. PMID- 26836565 TI - General study of asymmetrical crossed Czerny-Turner spectrometer. AB - A study of the spectrum resolution, wavelength range, and primary aberration of the asymmetrical crossed Czerny-Turner spectrometer is presented by deducing the relationship between them and structural parameters of the spectrometer in a new way of thinking based on simple but effective geometric models. The analysis was verified in an experiment and simulation performed on the optical design program ZEMAX, and the obtained results agree with the analysis. Owing to the analysis, initial designed parameters of the spectrometer were given and then optimized by ZEMAX; with the instruction of the study, a small adjustment was made in the actual alignment to obtain the desired final spectrometer. The spectrometer successfully measured the last four characteristic peaks of the Raman spectrum of CCL4, which demonstrates that the research provides important guidance to the design and alignment of an asymmetrical crossed Czerny-Turner spectrometer. PMID- 26836566 TI - Dielectric elastomer stack actuator-based autofocus fluid lens. AB - Extremely small cameras and many cell phones simply do not have enough room to allow users to move a rigid lens the distance required for a varying range of focal lengths. An adaptive liquid lens, however, enables small cameras to focus without needing extra room. An autofocus liquid lens provides several advantages over a traditional lens in terms of efficiency, cost, compactness, and flexibility. But one of the main challenges in these lenses is a high driving voltage requirement of around at least 1.8 kV. In this paper, we propose a new design of a liquid lens based on a dielectric elastomer stack actuator (DESA), which significantly overcomes the aforementioned existing problem. The lens consists of a frame (a thin DESA membrane with a hole in the middle), silicon oil, and water. A voltage range is applied on the membrane in order to change the hole dimension. Due to change of hole dimension, a change in meniscus occurs that changes the focal length of the lens. In this research work, various experimental results are achieved by configuring two DESA with different active areas. Depending on the active area of the membrane, the length of the laser beam on the plane varies from 6 to 35 mm, and the driving voltage is in the range of 50-750 V. PMID- 26836567 TI - Inverse solutions for a Risley prism scanner with iterative refinement by a forward solution. AB - Risley prism scanners are increasingly used for laser beam steering due to their wide angular scanning range and high resolution. However, the inverse problem, which focuses on obtaining the required prisms' orientations for a given target position, has not been perfectly solved so far. The existing inverse solutions are not accurate or efficient enough for high-accuracy and real-time tracking. An iterative method that combines an approximate inverse solution with an iterative refinement by the forward solution is set forth in this paper. Two case studies indicate that the rotation motions of Risley prism pairs controlled by iterative solutions can slew the beam to create the desired tracking pattern quickly and accurately. Based on this method, a Risley prism scanner developed as a standard trajectory generator is implemented for the error measurement of a robotic manipulator in our experiments. The simulation and experimental results show that the inverse solution for one target point can be obtained within nine iterations for a prescribed tracking error threshold. PMID- 26836568 TI - Design and tolerance of a free-form optical system for an optical see-through multi-focal-plane display. AB - By elegantly combining recent advancements of free-form optical technology and multi-focal-plane (MFP) display technology, we developed a high-performance true 3D augmented reality (AR) display that is capable of rendering a large volume of 3D scenes with accurate focus cues; this display overcomes the accommodation convergence discrepancy problem in conventional AR display. In this paper, we concentrate on various aspects of engineering challenges in the design and integration of a free-form optical see-through eyepiece with MFP technology for our AR display prototype. We present the design and optimization strategy in coupling free-form optics with a rotational-symmetric lens system to achieve high image quality. A comprehensive tolerance analysis of this complicated optical system is also presented, including an effective tolerance method for random surface figure errors on aspheric and free-form surfaces. Finally, the image quality of the virtual display is evaluated, which shows the as-built performance matches very well with the optical design results and tolerance analysis. PMID- 26836569 TI - The Anatomy of a Career in Science. PMID- 26836570 TI - Isolated, relative aproverbia without focal lesion. AB - We have seen a patient with a profound, isolated, and quite selective deficit in proverb interpretation-aproverbia. The patient presented to us after an anoxic brain injury with aproverbia. Interestingly, the aproverbia appeared to be premorbid to the presenting event. Furthermore, the patient had no brain lesion that has been associated or even proposed as a cause of deficit in proverb or metaphor interpretation. The patient did have acute bilateral hippocampi lesions and associated severe anterograde amnesia, but he retained good retrograde memory with which he is able to give good, logical but concrete explanations for proverbs. This case highlights the need, importance, and interest in further neuropsychologic, imaging and functional studies of proverb and interpretation in patients and normal subjects populations. PMID- 26836572 TI - Halogen-Bond-Templated [2+2] Photodimerization in the Solid State: Directed Synthesis and Rare Self-Inclusion of a Halogenated Product. AB - A ditopic halogen-bond acceptor organizes a diiodooctafluorostilbene for a [2+2] photodimerization reaction to take place between two stilbene molecules in the solid state. The resultant cyclobutane product is functionalized with halogen atoms and undergoes self-assembly to form a channel-type host-guest compound that exhibits a very rare form of self-inclusion. PMID- 26836574 TI - Alkali-Metal-Ion-Assisted Hydrogen Atom Transfer in the Homocysteine Radical. AB - Intramolecular hydrogen atom transfer (HAT) was examined in homocysteine (Hcy) thiyl radical/alkali metal ion complexes in the gas phase by combination of experimental techniques (ion-molecule reactions and infrared multiple photon dissociation spectroscopy) and theoretical calculations. The experimental results unequivocally show that metal ion complexation (as opposed to protonation) of the regiospecifically generated Hcy thiyl radical promotes its rapid isomerisation into an alpha-carbon radical via HAT. Theoretical calculations were employed to calculate the most probable HAT pathway and found that in alkali metal ion complexes the activation barrier is significantly lower, in full agreement with the experimental data. This is, to our knowledge, the first example of a gas phase thiyl radical thermal rearrangement into an alpha-carbon species within the same amino acid residue and is consistent with the solution phase behaviour of Hcy radical. PMID- 26836575 TI - Enantioselective Access to Spirocyclic Sultams by Chiral Cp(x) -Rhodium(III) Catalyzed Annulations. AB - Chiral spirocyclic sultams are a valuable compound class in organic and medicinal chemistry. A rapid entry to this structural motif involves a [3+2] annulation of an N-sulfonyl ketimine and an alkyne. Although the directing-group properties of the imino group for C-H activation have been exploited, the developments of related asymmetric variants have remained very challenging. The use of rhodium(III) complexes equipped with a suitable atropchiral cyclopentadienyl ligand, in conjunction with a carboxylic acid additive, enables an enantioselective and high yielding access to such spirocyclic sultams. PMID- 26836576 TI - Transition-Metal-Mediated Cleavage of Fluoro-Silanes under Mild Conditions. AB - Si-F bond cleavage of fluoro-silanes was achieved by transition-metal complexes under mild and neutral conditions. The Iridium-hydride complex [Ir(H)(CO)(PPh3 )3 ] was found to readily break the Si-F bond of the diphosphine- difluorosilane {(o Ph2 P)C6 H4 }2 Si(F)2 to afford a silyl complex [{[o-(iPh2 P)C6 H4 ]2 (F)Si}Ir(CO)(PPh3 )] and HF. Density functional theory calculations disclose a reaction mechanism in which a hypervalent silicon species with a dative Ir->Si interaction plays a crucial role. The Ir->Si interaction changes the character of the H on the Ir from hydridic to protic, and makes the F on Si more anionic, leading to the formation of H(delta+) ???F(delta-) interaction. Then the Si-F and Ir-H bonds are readily broken to afford the silyl complex and HF through sigma bond metathesis. Furthermore, the analogous rhodium complex [Rh(H)(CO)(PPh3 )3 ] was found to promote the cleavage of the Si-F bond of the triphosphine monofluorosilane {(o-Ph2 P)C6 H4 }3 Si(F) even at ambient temperature. PMID- 26836577 TI - One-Pot Sequential Propargylation/Cycloisomerization: A Facile [4+2] Benzannulation Approach to Carbazoles. AB - A novel one-pot [4+2]-benzannulation approach to substituted carbazoles is accomplished by acid-catalyzed C3-propargylation of 2-alkenyl/aryl indoles with 1 aryl propargylic alcohols, followed by cycloisomerization. A variety of 2 alkenylated indoles and 2-aryl/heteroaryl indoles successfully participated in this tandem reaction with 1-aryl/heteroaryl propargylic alcohols to provide diversely substituted and annulated carbazoles, as well as an aza[5]helicene. PMID- 26836571 TI - A Geospatial Analysis of Severe Firearm Injuries Compared to Other Injury Mechanisms: Event Characteristics, Location, Timing, and Outcomes. AB - OBJECTIVES: Relatively little is known about the context and location of firearm injury events. Using a prospective cohort of trauma patients, we describe and compare severe firearm injury events to other violent and nonviolent injury mechanisms regarding incident location, proximity to home, time of day, spatial clustering, and outcomes. METHODS: This was a secondary analysis of a prospective cohort of injured children and adults with hypotension or Glasgow Coma Scale score <= 8, injured by one of four primary injury mechanisms (firearm, stabbing, assault, and motor vehicle collision [MVC]) who were transported by emergency medical services to a Level I or II trauma center in 10 regions of the United States and Canada from January 1, 2010, through June 30, 2011. We used descriptive statistics and geospatial analyses to compare the injury groups, distance from home, outcomes, and spatial clustering. RESULTS: There were 2,079 persons available for analysis, including 506 (24.3%) firearm injuries, 297 (14.3%) stabbings, 339 (16.3%) assaults, and 950 (45.7%) MVCs. Firearm injuries resulted in the highest proportion of serious injuries (66.3%), early critical resources (75.3%), and in-hospital mortality (53.5%). Injury events occurring within 1 mile of a patient's home included 53.9% of stabbings, 49.2% of firearm events, 41.3% of assaults, and 20.0% of MVCs; the non-MVC events frequently occurred at home. While there was geospatial clustering, 94.4% of firearm events occurred outside of geographic clusters. CONCLUSIONS: Severe firearm events tend to occur within a patient's own neighborhood, often at home, and generally outside of geospatial clusters. Public health efforts should focus on the home in all types of neighborhoods to reduce firearm violence. PMID- 26836578 TI - Cancer Immunotherapy: Selected Targets and Small-Molecule Modulators. AB - There is a significant amount of excitement in the scientific community around cancer immunotherapy, as this approach has renewed hope for many cancer patients owing to some recent successes in the clinic. Currently available immuno-oncology therapeutics under clinical development and on the market are mostly biologics (antibodies, proteins, engineered cells, and oncolytic viruses). However, modulation of the immune system with small molecules offers several advantages that may be complementary and potentially synergistic to the use of large biologicals. Therefore, the discovery and development of novel small-molecule modulators is a rapidly growing research area for medicinal chemists working in cancer immunotherapy. This review provides a brief introduction into recent trends related to selected targets and pathways for cancer immunotherapy and their small-molecule pharmacological modulators. PMID- 26836579 TI - The mammalian complement system as an epitome of host-pathogen genetic conflicts. AB - The complement system is an innate immunity effector mechanism; its action is antagonized by a wide array of pathogens and complement evasion determines the virulence of several infections. We investigated the evolutionary history of the complement system and of bacterial-encoded complement-interacting proteins. Complement components targeted by several pathogens evolved under strong selective pressure in primates, with selection acting on residues at the contact interface with microbial/viral proteins. Positively selected sites in CFH and C4BPA account for the human specificity of gonococcal infection. Bacterial interactors, evolved adaptively as well, with selected sites located at interaction surfaces with primate complement proteins. These results epitomize the expectation under a genetic conflict scenario whereby the host's and the pathogen's genes evolve within binding avoidance-binding seeking dynamics. In silico mutagenesis and protein-protein docking analyses supported this by showing that positively selected sites, both in the host's and in the pathogen's interacting partner, modulate binding. PMID- 26836580 TI - Induction of systemic disease resistance in Nicotiana benthamiana by the cyclodipeptides cyclo (l-Pro-l-Pro) and cyclo (d-Pro-d-Pro). AB - Cyclodipeptides, formed from two amino acids by cyclodehydration, are produced naturally by many organisms, and are known to possess a large number of biological activities. In this study, we found that cyclo (l-Pro-l-Pro) and cyclo (d-Pro-d-Pro) (where Pro is proline) could induce defence responses and systemic resistance in Nicotiana benthamiana. Treatment with the two cyclodipeptides led to a reduction in disease severity by Phytophthora nicotianae and Tobacco mosaic virus (TMV) infections compared with controls. Both cyclopeptides triggered stomatal closure, induced reactive oxygen species production and stimulated cytosolic calcium ion and nitric oxide production in guard cells. In addition, the application of cyclodipeptides significantly up-regulated the expression of the plant defence gene PR-1a and the PR-1a protein, and increased cellular salicylic acid (SA) levels. These results suggest that the SA-dependent defence pathway is involved in cyclodipeptide-mediated pathogen resistance in N. benthamiana. We report the systemic resistance induced by cyclodipeptides, which sheds light on the potential of cyclodipeptides for the control of plant diseases. PMID- 26836581 TI - Solution-Blown Core-Shell Self-Healing Nano- and Microfibers. AB - Self-healing microfibers with core-shell geometry were studied. A commercial binary epoxy was encased in solution-blown polymer nano-/microfibers in the 0.2 2.6 MUm diameter range. The core-shell microfibers were formed by coaxial nozzles, which encapsulated the epoxy resin and its hardener in separate cores. Solution blowing, the fiber-forming process used in this work, was at least 30 times faster than the electrospinning method used previously and has already been scaled up to the industrial level. These core-shell microfibers show self-healing capability, in which epoxy and hardener are released from the cores of damaged fibers, resulting in polymerization. The epoxy used had a higher strength and shorter solidification time than poly(dimethylsiloxane) (PDMS) used previously. Also, the larger fiber diameters in the present study facilitated faster release of the epoxy resin and its hardener from the fiber cores, shortening the solidification time in comparison to the previous studies. Blister tests were conducted, which measured the adhesion energy of microfiber mats to substrates and the cohesion energy between layers of microfiber mats before and after fatigue damage followed by self-healing. PMID- 26836582 TI - The influence of pH and fluid dynamics on the antibacterial efficacy of 45S5 Bioglass. AB - In recent years, there has been considerable interest in the potential antibacterial properties that bioactive glasses may possess. However, there have been several conflicting reports on the antibacterial efficacy of 45S5 Bioglass((r)). Various mechanisms regarding its mode of action have been proposed, such as changes in the environmental pH, increased osmotic pressure, and 'needle-like' sharp glass debris which could potentially damage prokaryotic cell walls and thus inactivate bacteria. In this current study, a systematic investigation was undertaken on the antibacterial efficacy of 45S5 Bioglass((r)) on Escherichia coli NCTC 10538 and Staphylococcus aureus ATCO 6538 under a range of clinically relevant scenarios including varying Bioglass((r)) concentration, direct and indirect contact between Bioglass((r)) and microorganisms, static and shaking incubation conditions, elevated and neutralised pH environments. The results demonstrated that, under elevated pH conditions, Bioglass((r)) particles have no antibacterial effect on S. aureus while a concentration dependent antibacterial effect against E. coli was observed. However, the antibacterial activity ceased when the pH of the media was neutralised. The results of this current study, therefore, suggest that the mechanism of antibacterial activity of Bioglass((r)) is associated with changes in the environmental pH; an environment that is less likely to occur in vivo due to buffering of the system. PMID- 26836583 TI - Successful Treatment of Segmental Vitiligo in Children with the Combination of 1 mm Minigrafts and Phototherapy. AB - BACKGROUND: Minigrafts using a 1-mm biopsy punch (1-mm minigrafts) are being increasingly used to treat vitiligo. However, there have been few reports of the use of 1-mm minigrafts in pediatric patients. OBJECTIVE: To examine the effectiveness of combination therapy with 1-mm minigrafts and phototherapy in children with segmental vitiligo. METHODS: Minigrafts were placed in 13 patients aged <=16 years with segmental vitiligo. Following surgery, 11 patients underwent irradiation with excimer laser light and 2 with narrow-band ultraviolet B light. RESULTS: A mean repigmentation of 81.6% was obtained. A particularly high mean repigmentation of 87.9% was seen in patients aged <=12 years, indicating greater efficacy in these patients than in patients aged >=13 years (mean, 67.5%). Although a transient cobblestone appearance occurred as an adverse effect, it improved over time. CONCLUSIONS: Combined treatment of segmental vitiligo with 1 mm minigrafts and phototherapy can be performed safely and is highly effective in young patients. PMID- 26836584 TI - Crisis Standard Needed for Anthrax Medical Countermeasure Screening. PMID- 26836585 TI - Clinical and Immunologic Features of Ultra-Short Celiac Disease. AB - BACKGROUND & AIMS: The clinical effects of gluten-sensitive enteropathy with villous atrophy limited to the duodenal bulb (D1) have not been delineated in adults with celiac disease. We investigated the sensitivity of D1 biopsy analysis in the detection of celiac disease, the number and sites of biopsies required to detect ultra-short celiac disease (USCD, villous atrophy limited to D1), and the clinical phenotype of USCD. METHODS: We performed a prospective study of 1378 patients (mean age, 50.3 y; 62% female) who underwent endoscopy at a tertiary medical center in the United Kingdom from 2008 through 2014; routine duodenal biopsy specimens were collected from D1 and the second part of the duodenum (D2). Quadrantic D1 biopsy specimens were collected from 171 consecutive patients with a high suspicion of celiac disease (mean age, 46.5 y; 64% female). Clinical data from patients diagnosed with USCD, based on biopsy analysis, were compared with those from patients with conventional celiac disease (CCD) (villous atrophy beyond D1) and individuals without celiac disease (controls). The number of intraepithelial lymphocytes (IELs) and immune phenotypes were compared between D1 vs D2 in patients with celiac disease. RESULTS: Of the 1378 patients assessed, 268 (19.4%) were diagnosed with celiac disease; 9.7% of these patients had villous atrophy confined to D1 (USCD; P < .0001). Collection of a single additional biopsy specimen from any D1 site increased the sensitivity of celiac disease detection by 9.3%-10.8% (P < .0001). Patients with USCD were younger (P = .03), had lower titers of tissue transglutaminase antibody (P = .001), and less frequently presented with diarrhea (P = .001) than patients with CCD. Higher proportions of patients with CCD had ferritin deficiency (P = .007) or folate deficiency (P = .003) than patients with USCD or controls. Patients with celiac disease had a median of 50 IELs/100 enterocytes in D1 and a median of 48 IELs/100 enterocytes (P = .7) in D2. The phenotype of IELs from patients with D1 celiac disease was indistinguishable from those of patients with D2 celiac disease. CONCLUSIONS: Collection of a single additional biopsy specimen from any site in the D1 intestine increases the sensitivity of detection for celiac disease. Patients with USCD may have early stage or limited celiac disease, with a mild clinical phenotype and infrequent nutritional deficiencies. PMID- 26836587 TI - Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-analysis. AB - BACKGROUND & AIMS: Eradication of Helicobacter pylori infection has been reported to reduce the risk of gastric cancer among asymptomatic individuals in high-risk areas. The magnitude of benefit of H pylori eradication in populations with different levels of gastric cancer risk and in different clinical scenarios is unclear. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies to investigate the effects of H pylori eradication on the incidence of gastric cancer. METHODS: We searched PubMed, Cochrane Library, and ClinicalTrials.gov, reviewing titles and abstracts of studies of the effects of eradication of H pylori infection on risk of gastric cancer, through May 2015. We also searched bibliographies of included studies, related reviews, and abstracts presented at Digestive Disease Week. Twenty-four eligible studies (22 research manuscripts and 2 abstracts) were included in our meta-analysis (715 incident gastric cancers among a total of 48,064 individuals/340,255 person-years). We assessed the effects, as well as their modification by baseline gastric cancer incidence, study design (randomized trial vs observational study), clinical scenario (asymptomatic infected individuals vs individuals after endoscopic resection of early gastric cancer), demographic characteristics of patients (age and sex), and duration of follow-up. RESULTS: After adjustment for baseline gastric cancer incidence, individuals with eradication of H pylori infection had a lower incidence of gastric cancer than those who did not receive eradication therapy (pooled incidence rate ratio = 0.53; 95% confidence interval: 0.44-0.64). There was little heterogeneity among studies. Baseline gastric cancer incidence modified the benefit of H pylori eradication (P = .037 for interaction); the incidence rate ratio of gastric cancer decreased in a nonlinear fashion with increasing baseline incidence of gastric cancer (P = .018, in comparison with the linear model). The benefit also modestly increased with age (P = .023 for interaction), but this might be due to correlation between age and baseline gastric cancer incidence. Eradication provided significant benefit for asymptomatic infected individuals (pooled incidence rate ratio, 0.62; 95% CI: 0.49-0.79) and individuals after endoscopic resection of gastric cancers (pooled incidence rate ratio, 0.46; 95% CI: 0.35 0.60). The benefits of H pylori eradication did not differ with study design, sex, or follow-up period. CONCLUSIONS: In a systematic review and meta-analysis, we associated eradication of H pylori infection with a reduced incidence of gastric cancer. The benefits of eradication vary with baseline gastric cancer incidence, but apply to all levels of baseline risk. PMID- 26836586 TI - Effects of Cancer Stage and Treatment Differences on Racial Disparities in Survival From Colon Cancer: A United States Population-Based Study. AB - BACKGROUND & AIMS: We evaluated differences in treatment of black vs white patients with colon cancer and assessed their effects on survival, based on cancer stage. METHODS: We collected data from the Surveillance, Epidemiology, and End Results-Medicare database and identified 6190 black and 61,951 white patients with colon cancer diagnosed from 1998 through 2009 and followed up through 2011. Three sets of 6190 white patients were matched sequentially, using a minimum distance strategy, to the same set of 6190 black patients based on demographic (age; sex; diagnosis year; and Surveillance, Epidemiology, and End Results registry), tumor presentation (demographic plus comorbidities, tumor stage, grade, and size), and treatment (presentation plus therapies) variables. We conducted sensitivity analyses to explore the effects of socioeconomic status in a subcohort that included 2000 randomly selected black patients. Racial differences in treatment were assessed using a logistic regression model; their effects on racial survival disparity were evaluated using the Kaplan-Meier method and the Cox proportional hazards model. RESULTS: After patients were matched for demographic variables, the absolute 5-year difference in survival between black and white patients was 8.3% (white, 59.2% 5-y survival; blacks, 50.9% 5-y survival) (P < .0001); this value decreased significantly, to 5.0% (P < .0001), after patients were matched for tumor presentation, and decreased to 4.9% (P < .0001) when patients were matched for treatment. Differences in treatment therefore accounted for 0.1% of the 8.3% difference in survival between black and white patients. After patients were matched for tumor presentation, racial disparities were observed in almost all types of treatment; the disparities were most prominent for patients with advanced-stage cancer (stages III or IV, up to an 11.1% difference) vs early stage cancer (stages I or II, up to a 4.3% difference). After patients were matched for treatment, there was a greater reduction in disparity for black vs white patients with advanced-stage compared with early-stage cancer. In sensitivity analyses, the 5-year racial survival disparity was 7.7% after demographic match, which was less than the 8.3% observed in the complete cohort. This reduction likely was owing to the differences between the subcohort and the complete cohort in those variables that were not included in the demographic match. This value was reduced to 6.5% (P = .0001) after socioeconomic status was included in the demographic match. The difference decreased significantly to 2.8% (P = .090) after tumor presentation match, but was not reduced further after treatment match. CONCLUSIONS: We observed significant disparities in treatment and survival of black vs white patients with colon cancer. The disparity in survival appears to have been affected more strongly by tumor presentation at diagnosis than treatment. The effects of treatment differences on disparities in survival were greater for patients with advanced-stage vs early-stage cancer. PMID- 26836589 TI - Anharmonic Computations Meet Experiments (IR, Raman, Neutron Diffraction) for Explaining the Behavior of 1,3,5-Tribromo-2,4,6-trimethylbenzene. AB - In the present paper we first show the experimental Raman, infrared, and neutron INS spectra of tribromomesitylene (TBM) measured in the range 50-3200 cm(-1) using crystalline powders at 6 or 4 K. Then, the bond lengths and angles determined by neutron diffraction using a TBM single crystal at 14 K are compared to the computed ones at different levels of theory. Anharmonic computations were then performed on the relaxed structure using the VPT2 approach, and for the lowest normal modes, the HRAO model has led to a remarkable agreement for the assignment of the experimental signatures. A particularity appears for frequencies below 150 cm(-1), and in particular for those concerning the energy levels of "hindered rotation" of the three methyl groups, they must be calculated for one-dimensional symmetrical tops independent of the frame vibrations. This fact is consistent with the structure established by neutron diffraction: the protons of the methyl groups undergoing huge "libration" motions are widely spread in space. The values of the transitions between the librational levels determined by inelastic neutron scattering indicate that the hindering potentials are mainly due to intermolecular interactions different for each methyl group in the triclinic cell. PMID- 26836590 TI - Hexasubstituted Benzenes with Ultrastrong Dipole Moments. AB - Hexasubstituted benzenes have been synthesized with the highest known dipole moments, as determined by dielectric spectroscopy and DFT methods. Based on the preparation of 4,5-diamino-3,6-dibromophthalonitrile, combined with a novel method to synthesize dihydrobenzimidazoles, these benzene derivatives have dipole moments in excess of 10 debye. Such dipole moments are desirable in ferroelectrics, nonlinear optics, and in organic photovoltaics. Structure determination was achieved through single-crystal X-ray crystallography, and the optical properties were determined by UV/Vis absorption and fluorescence spectroscopy. PMID- 26836591 TI - Transforming Living Kidney Donation with a Comprehensive Strategy. AB - Matthew Allen and Peter Reese argue that evidence-based efforts should be implemented to expand living kidney donation. PMID- 26836593 TI - Reliability of accelerometry to assess impact loads of jumping and landing tasks. AB - Overuse injuries, resulting from repetitive subacute impact loading, are a problem in high-performance sports. Monitoring of impact loading may aid in the prevention of these injuries. The current study aimed to establish the intra-day and inter-day reliability of a tri-axial accelerometer to assess impact loading during jumping and landing tasks. Twelve participants wore an accelerometer on their upper and lower back. They performed a continuous hopping task as well as drop landings and rebound jumps from three drop heights (37.5, 57.5 and 77.5 cm), peak resultant acceleration (PRA) was calculated for all tasks. The tasks were performed twice, one week apart at the same time of day. The difference in the mean, intra-class correlation coefficient, coefficient of variation and Cohen's effect size were calculated as measures of reliability. PRA showed good intra-day reliability for the hopping task. Inter-day reliability of the PRA was moderate to good across all tasks. Reliability of PRA was slightly higher when accelerations were recorded on the lower back compared to the upper back. To assess impact loading, during continuous hopping, drop landings and rebound jumps, PRA recorded at both the upper and lower back appears to be a reliable measure. PMID- 26836592 TI - The Argyre Region as a Prime Target for in situ Astrobiological Exploration of Mars. AB - At the time before ~3.5 Ga that life originated and began to spread on Earth, Mars was a wetter and more geologically dynamic planet than it is today. The Argyre basin, in the southern cratered highlands of Mars, formed from a giant impact at ~3.93 Ga, which generated an enormous basin approximately 1800 km in diameter. The early post-impact environment of the Argyre basin possibly contained many of the ingredients that are thought to be necessary for life: abundant and long-lived liquid water, biogenic elements, and energy sources, all of which would have supported a regional environment favorable for the origin and the persistence of life. We discuss the astrobiological significance of some landscape features and terrain types in the Argyre region that are promising and accessible sites for astrobiological exploration. These include (i) deposits related to the hydrothermal activity associated with the Argyre impact event, subsequent impacts, and those associated with the migration of heated water along Argyre-induced basement structures; (ii) constructs along the floor of the basin that could mark venting of volatiles, possibly related to the development of mud volcanoes; (iii) features interpreted as ice-cored mounds (open-system pingos), whose origin and development could be the result of deeply seated groundwater upwelling to the surface; (iv) sedimentary deposits related to the formation of glaciers along the basin's margins, such as evidenced by the ridges interpreted to be eskers on the basin floor; (v) sedimentary deposits related to the formation of lakes in both the primary Argyre basin and other smaller impact derived basins along the margin, including those in the highly degraded rim materials; and (vi) crater-wall gullies, whose morphology points to a structural origin and discharge of (wet) flows. PMID- 26836588 TI - Variants in TRIM22 That Affect NOD2 Signaling Are Associated With Very-Early Onset Inflammatory Bowel Disease. AB - BACKGROUND & AIMS: Severe forms of inflammatory bowel disease (IBD) that develop in very young children can be caused by variants in a single gene. We performed whole-exome sequence (WES) analysis to identify genetic factors that might cause granulomatous colitis and severe perianal disease, with recurrent bacterial and viral infections, in an infant of consanguineous parents. METHODS: We performed targeted WES analysis of DNA collected from the patient and her parents. We validated our findings by a similar analysis of DNA from 150 patients with very early-onset IBD not associated with known genetic factors analyzed in Toronto, Oxford, and Munich. We compared gene expression signatures in inflamed vs noninflamed intestinal and rectal tissues collected from patients with treatment resistant Crohn's disease who participated in a trial of ustekinumab. We performed functional studies of identified variants in primary cells from patients and cell culture. RESULTS: We identified a homozygous variant in the tripartite motif containing 22 gene (TRIM22) of the patient, as well as in 2 patients with a disease similar phenotype. Functional studies showed that the variant disrupted the ability of TRIM22 to regulate nucleotide binding oligomerization domain containing 2 (NOD2)-dependent activation of interferon beta signaling and nuclear factor-kappaB. Computational studies demonstrated a correlation between the TRIM22-NOD2 network and signaling pathways and genetic factors associated very early onset and adult-onset IBD. TRIM22 is also associated with antiviral and mycobacterial effectors and markers of inflammation, such as fecal calprotectin, C-reactive protein, and Crohn's disease activity index scores. CONCLUSIONS: In WES and targeted exome sequence analyses of an infant with severe IBD characterized by granulomatous colitis and severe perianal disease, we identified a homozygous variant of TRIM22 that affects the ability of its product to regulate NOD2. Combined computational and functional studies showed that the TRIM22-NOD2 network regulates antiviral and antibacterial signaling pathways that contribute to inflammation. Further study of this network could lead to new disease markers and therapeutic targets for patients with very early and adult-onset IBD. PMID- 26836594 TI - The influence of Rubus idaeus and Rubus caesius leaf extracts on platelet aggregation in whole blood. Cross-talk of platelets and neutrophils. AB - Recently, polyphenols have gained attention as potential natural cardioprotective therapeutics, due to their antiplatelet, anti-inflammatory and anticoagulant activity. Species belonging to the genus Rubus sp. have been reported to be a source of polyphenolic compounds with antioxidative proprieties and beneficial biological activities. This study investigates the effects of leaf extracts obtained from red raspberry (Rubus idaeus L.) and European dewberry (Rubus caesius L.) on the reactivity of blood platelets. In ADP-stimulated blood, raspberry and dewberry extracts (15 ug/ml) markedly decreased platelet surface membrane expression of activated GPIIbIIIa receptor by 16% and 21%, respectively (P < 0.01) and significantly inhibited platelet aggregation (by 31-41% for raspberry and by 38-55% for dewberry, P < 0.01). In platelet-rich plasma (PRP), the extracts had no effect on ADP-induced platelet aggregation. The effectiveness of the extracts in whole blood and the lack of their activity in PRP indicate that leukocytes are likely to participate in the platelet response to the extracts. Our experiments show that the extracts significantly reduced the amount of free radicals released by activated neutrophils in whole blood (P < 0.001), as well as in suspensions of isolated neutrophils (P < 0.05). Moreover, the reduced number of neutrophils leads to the decreased efficiency of the extracts in the inhibition of platelet aggregation. In summary, our findings show that the raspberry and dewberry leaf extracts considerably modulated blood platelet reactivity in whole blood: they influenced blood platelet aggregation, possibly via the modulation of the redox status dependent on the oxidative activity of neutrophils. PMID- 26836595 TI - Ending Gun Violence: Putting People Before Politics to Expand Research About Gun Violence. PMID- 26836596 TI - Application of Transformational Leadership Principles in the Development and Integration of Palliative Care Within an Advanced Heart Failure Program. AB - Heart failure (HF) is a major health problem in United States, and it has reached epidemic proportions. Heart failure is associated with significant morbidity, mortality, and cost. Although the prognosis of HF is worse than many forms of cancer, many patients, families, and clinicians are unaware of the dire prognosis. As the disease progress to advanced HF, patients are faced with many challenges, such as poor quality of life due to worsening symptoms and frequent hospitalizations. Heart failure management adds significant financial burden to the health care system. Palliative care can be integrated into HF care to improve quality of life and symptom management and to address physical, spiritual, and psychosocial needs of patients and families. Palliative care can be used concurrently with or independent of curative or life-prolonging HF therapies. Transformational leadership principles were used to guide the development of a plan to enhance integration of palliative care within traditional advanced HF care. PMID- 26836597 TI - Using Procalcitonin in Septic Shock to Guide Antibacterial Therapy. AB - Over the last decade, the biomarkers procalcitonin and C-reactive protein have gained interest in sepsis research. Procalcitonin is a unique biomarker that is specific to bacterial infection and has demonstrated utility in the risk stratification of patients with potential life-threatening bacterial infections. In addition, procalcitonin has been documented as having a role in reducing the rate of unnecessary antibiotics while positively impacting antibiotic resistance rates and cost savings. The purposes of this review article are to discuss the clinical relevance of C-reactive protein and procalcitonin as diagnostic and prognostic markers for sepsis with a focus on the use of serial procalcitonin levels as a component of antibiotic stewardship programs. The federal government has recently become invested in combating the progression of antibiotic resistance; a 5-year national plan has been developed to address these concerns. Establishing a reliable antibiotic stewardship program is one of the goals of this national plan. PMID- 26836600 TI - Thank you DCCN Reviewers 2015. PMID- 26836598 TI - An Innovative Approach to Improving the Accuracy of Delirium Assessments Using the Confusion Assessment Method for the Intensive Care Unit. AB - BACKGROUND: Delirium occurs in up to 80% of intensive care unit (ICU) patients. Despite its prevalence in this population, there continues to be inaccuracies in delirium assessments. In the absence of accurate delirium assessments, delirium in critically ill ICU patients will remain unrecognized and will lead to negative clinical and organizational outcomes. OBJECTIVES: The goal of this quality improvement project was to facilitate sustained improvement in the accuracy of delirium assessments among all ICU patients including those who were sedate or agitated. METHODS: A pretest-posttest design was used to evaluate the effectiveness of a program to improve the accuracy of delirium screenings among patients admitted to a medical ICU or coronary care unit. RESULTS: Two hundred thirty-six delirium assessment audits were completed during the baseline period and 535 during the postintervention period. Compliance with performing at least 1 delirium assessment every shift was 85% at baseline and improved to 99% during the postintervention period. Baseline assessment accuracy was 70.31% among all patients and 53.49% among sedate and agitated patients. Postintervention assessment accuracy improved to 95.51% for all patients and 89.23% among sedate and agitated patients. CONCLUSION: The results from this project suggest the effectiveness of the program in improving assessment accuracy among difficult-to assess patients. Further research is needed to demonstrate the effectiveness of this model across other critical care units, patient populations, and organizations. PMID- 26836601 TI - The Effect of Chlorhexidine Bathing on Rates of Nosocomial Infections Among the Critically Ill Population: An Analysis of Current Clinical Research and Recommendations for Practice. AB - BACKGROUND: This literature review examined the current research of evidence based standards to evaluate the effectiveness of daily bathing with 2% chlorhexidine gluconate (CHG; manufactured by Sage Products Inc) compared with traditional non-antimicrobial bathing on reducing the incidence of nosocomial infections in the critically ill population. OBJECTIVE/AIM: The objective of this article is 3-fold: first, to provide a background on the increased susceptibility to pathogens that have become endemic in many intensive care units; second, to challenge health care providers to question current practice and consider additional ways to ensure safety and better outcomes in the critically ill population; and third, to provide health care providers with clinical evidence to avoid infection control failures. METHOD: To determine whether published standards for daily patient bathing exist, a search was conducted of bibliographic databases for articles published within the last 5 years (2010 2015). Ultimately, 3 large multicenter cluster randomized controlled studies were chosen to compare the outcomes of daily bathing with 2% CHG cloths with those of daily bathing with non-antimicrobial cloths. RESULTS: The side-by-side comparison of the studies revealed similar outcomes, but with variations in study design. Climo et al (2013) and Milestone et al (2013) recommended the implementation of daily bathing with 2% CHG washcloths as a strategy to decrease nosocomial infections in the critically ill population. Huang et al (2013) recommended universal decolonization as the most effective method to decrease nosocomial infections. DISCUSSION: The analysis of the 3 primary studies revealed similar findings that support the recommendation for the implementation of daily bathing with 2% CHG in the critically ill population. Further research will inform clinicians on the susceptibility of bacteria to CHG and the probability of creating microbial resistance. PMID- 26836603 TI - The Utility of the Candida Score in Patients With Sepsis. AB - BACKGROUND: Candida is a leading cause of infection in the intensive care unit. Colonization versus infection remains a challenge. A Candida Score (CS) of 3 or greater has been used to target antifungal therapy in surgical patients at risk of candidemia but has not been well evaluated in medical patients with sepsis. OBJECTIVES: The aim of this study was to assess utility of the CS in detecting candidemia early in patients with sepsis. METHODS: This was a secondary analysis of patients with sepsis (n = 77) who were followed up for development of new infections. Patients with known fungal infection at admission were excluded. Candida colonization was defined as Candida cultured from any baseline culture, except blood, as a part of routine clinical care. RESULTS: Candidemia was detected in 8 of 77 participants (10.4%; 4 [15.4%] with a CS >=3 and 4 [7.8%] with a CS <3). Demographic variables (age, race, sex) were similar among those who did and did not develop candidemia. Using the recommended CS of 3 or greater, sensitivity was (4/8) 50%, specificity was (47/69) 68.1%, positive predictive value was (4/26) 15.4%, and negative predictive value was (47/51) 92.2%. Baseline colonization was significantly higher among those who developed candidemia (50% vs 11.6%; P = .02), but no significant differences were observed among CS components or total scores. CONCLUSIONS: Despite a relatively poor sensitivity, a reasonable specificity with a strong negative predictive value makes this tool a viable option for screening medically ill patients who may require antifungal agents. The CS should be evaluated in a larger, more inclusive, medical population. PMID- 26836604 TI - Factors Influencing Registered Nurses' Decision to Activate an Adult Rapid Response Team in a Community Hospital. AB - BACKGROUND: One factor impacting patient outcomes in the acutely deteriorating patient is a delay by nursing staff to activate a rapid response team (RRT); however, a gap in knowledge exists concerning factors influencing activation of an RRT by nursing staff working in adult areas outside the medical-surgical and telemetry setting. OBJECTIVES: The purpose of this study was to examine beliefs and behaviors that influence registered nurses' decision to activate an adult rapid response team in a community hospital that includes 3 specialties: medical surgical and telemetry, peripartum, and psychiatric areas. METHODS: One hundred sixty-three nurses were surveyed using a 17-item Likert-style instrument to assess registered nurses' beliefs and attitudes on and barriers to utilizing an RRT. RESULTS: The survey was analyzed yielding 3 factors: RRT barriers, RRT positive/intent to activate, and patient management beliefs. Barriers cited by other research to activate RRT including criticism by the team and perception that the RRT increases workload or reduces skills were not found to be influential considerations. A significant difference was found among the 3 specialty groups related to RRT positive/intent to activate (F2,159 = 6.09, P = .003) and patient management beliefs (F2,159 = 5.87, P = .003). A strong negative correlation was found between years of experience as an RN and RRT barriers (rho161 = -0.250). DISCUSSION: Organizations should examine RRT activation delays particularly in the area of calls to covering physicians prior to RRT activations. Differences between specialty groups highlight the need for education across specialties on the recognition of the acutely deteriorating patient. The findings indicate that the inexperienced nurse requires support from experienced colleagues and temporary adjustments to workload during situations of acute deterioration of a patient. PMID- 26836606 TI - Leadership. PMID- 26836607 TI - Enrichment of specific electro-active microorganisms and enhancement of methane production by adding granular activated carbon in anaerobic reactors. AB - Direct interspecies electron transfer (DIET) via conductive materials can provide significant benefits to anaerobic methane formation in terms of production amount and rate. Although granular activated carbon (GAC) demonstrated its applicability in facilitating DIET in methanogenesis, DIET in continuous flow anaerobic reactors has not been verified. Here, evidences of DIET via GAC were explored. The reactor supplemented with GAC showed 1.8-fold higher methane production rate than that without GAC (35.7 versus 20.1+/-7.1mL-CH4/d). Around 34% of methane formation was attributed to the biomass attached to GAC. Pyrosequencing of 16S rRNA gene demonstrated the enrichment of exoelectrogens (e.g. Geobacter) and hydrogenotrophic methanogens (e.g. Methanospirillum and Methanolinea) from the biomass attached to GAC. Furthermore, anodic and cathodic currents generation was observed in an electrochemical cell containing GAC biomass. Taken together, GAC supplementation created an environment for enriching the microorganisms involved in DIET, which increased the methane production rate. PMID- 26836608 TI - Design of a new integrated chitosan-PAMAM dendrimer biosorbent for heavy metals removing and study of its adsorption kinetics and thermodynamics. AB - In this research, different generations of PAMAM-grafted chitosan as integrated biosorbents were successfully synthesized via step by step divergent growth approach of dendrimer. The synthesized products were utilized as adsorbents for heavy metals (Pb(2+) in this study) removing from aqueous solution and their reactive Pb(2+) removal potential was evaluated. The results showed that as synthesized products with higher generations of dendrimer, have more adsorption capacity compared to products with lower generations of dendrimer and sole chitosan. Adsorption capacity of as-prepared product with generation 3 of dendrimer is 18times more than sole chitosan. Thermodynamic and kinetic studies were performed for understanding equilibrium data of the uptake capacity and kinetic rate uptake, respectively. Thermodynamic and kinetic studies showed that Langmuir isotherm model and pseudo second order kinetic model are more compatible for describing equilibrium data of the uptake capacity and kinetic rate of the Pb(2+) uptake, respectively. PMID- 26836610 TI - Effects of Somatostatin Analogs and Dopamine Agonists on Insulin-Like Growth Factor 2-Induced Insulin Receptor Isoform A Activation by Gastroenteropancreatic Neuroendocrine Tumor Cells. AB - BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) express insulin-like growth factor (IGF)-related factors [IGF1, IGF2; insulin receptor (IR)-A, IR-B; IGF-binding protein (IGFBP) 1-3] as well as somatostatin (SSTRs) and dopamine D2 receptors (D2Rs). OBJECTIVES: To (1) compare mRNA expression of IGF-related factors in human pancreatic NET (panNET) cell lines with that in human GEP-NETs to evaluate the usefulness of these cells as a model for studying the IGF system in GEP-NETs, (2) determine whether panNET cells produce growth factors that activate IR-A, and (3) investigate whether somatostatin analogs (SSAs) and/or dopamine agonists (DAs) influence the production of these growth factors. METHODS: In panNET cells (BON-1 and QGP-1) and GEP-NETs, mRNA expression of IGF-related factors was measured by quantitative real-time PCR. Effects of the SSAs octreotide and pasireotide (PAS), the DA cabergoline (CAB), and the dopastatin BIM-23A760 (all 100 nM) were evaluated at the IGF2 mRNA and protein level (by ELISA) and regarding IR-A bioactivity (by kinase receptor activation assay) in panNET cells. RESULTS: panNET cells and GEP-NETs had comparable expression profiles of IGF-related factors. Especially in BON-1 cells, IGF2 and IR-A were most highly expressed. PAS + CAB inhibited IGF2 (-29.5 +/- 4.9%, p < 0.01) and IGFBP3 (-20.0 +/- 4.0%, p < 0.01) mRNA expression in BON-1 cells. In BON-1 cells, IGF2 protein secretion was significantly inhibited with BIM-23A760 ( 23.7 +/- 3.8%). BON-1- but not QGP-1- conditioned medium stimulated IR-A bioactivity. In BON-1 cells, IR-A bioactivity was inhibited by BIM-23A760 and PAS + CAB (-37.8 +/- 2.1% and -30.9 +/- 4.1%, respectively, p < 0.0001). CONCLUSIONS: (1) The BON-1 cell line is a representative model for studying the IGF system in GEP-NETs, (2) BON-1 cells produce growth factors (IGF2) activating IR-A, and (3) combined SSTR and D2R targeting with PAS + CAB and BIM-23A760 suppresses IGF2 induced IR-A activation. PMID- 26836609 TI - Conditioned Medium from Early-Outgrowth Bone Marrow Cells Is Retinal Protective in Experimental Model of Diabetes. AB - Bone marrow-derived cells were demonstrated to improve organ function, but the lack of cell retention within injured organs suggests that the protective effects are due to factors released by the cells. Herein, we tested cell therapy using early outgrowth cells (EOCs) or their conditioned media (CM) to protect the retina of diabetic animal models (type 1 and type 2) and assessed the mechanisms by in vitro study. Control and diabetic (db/db) mice (8 weeks of age) were randomized to receive a unique intravenous injection of 5*105EOCs or 0.25 ml thrice weekly tail-vein injections of 10x concentrated CM and Wystar Kyoto rats rendered diabetic were randomized to receive 0.50 ml thrice weekly tail-vein injections of 10x concentrated CM. Four weeks later, the animals were euthanized and the eyes were enucleated. Rat retinal Muller cells (rMCs) were exposed for 24 h to high glucose (HG), combined or not with EOC-conditioned medium (EOC-CM) from db/m EOC cultures. Diabetic animals showed increase in diabetic retinopathy (DR) and oxidative damage markers; the treatment with EOCs or CM infusions significantly reduced this damage and re-established the retinal function. In rMCs exposed to diabetic milieu conditions (HG), the presence of EOC-CM reduced reactive oxygen species production by modulating the NADPH-oxidase 4 system, thus upregulating SIRT1 activity and deacetylating Lys-310-p65-NFkappaB, decreasing GFAP and VEGF expressions. The antioxidant capacity of EOC-CM led to the prevention of carbonylation and nitrosylation posttranslational modifications on the SIRT1 molecule, preserving its activity. The pivotal role of SIRT1 on the mode of action of EOCs or their CM was also demonstrated on diabetic retina. These findings suggest that EOCs are effective as a form of systemic delivery for preventing the early molecular markers of DR and its conditioned medium is equally protective revealing a novel possibility for cell-free therapy for the treatment of DR. PMID- 26836612 TI - Supra hepatic inferior vena cava and right atrial thrombosis following a traffic car crash. AB - We present a case of nephrotic syndrome associated with right atrial and supra hepatic vein part of inferior vena caval thrombosis. This patient presented with dyspena, lower extremity edema and back pain after a vehicle accident and blunt trauma to the abdomen. Trauma should be considered not only as a thrombophilic pre-disposition, but also as a predisposing factor to IVC endothelium injury and thrombosis formation. Echocardiography revealed supra hepatic vein IVC thrombosis floating to the right atrium. A C-T scan with contrast also showed pulmonary artery emboli to the left upper lobe. With open heart surgery, the right atrial and IVC clot were extracted and the main left and right pulmonary arteries were evaluated for possible clot lodging. The patient had an uneventful postoperative recovery and thrombosis has not reoccurred with periodical follow-up examinations. PMID- 26836611 TI - Basic principles and practice of gastric cancer screening using high-definition white-light gastroscopy: Eyes can only see what the brain knows. AB - Endoscopic diagnosis of gastrointestinal tumors consists of the following processes: (i) detection; (ii) differential diagnosis; and (iii) quantitative diagnosis (size and depth) of a lesion. Although detection is the first step to make a diagnosis of the tumor, the lesion can be overlooked if an endoscopist has no knowledge of what an early-stage 'superficial lesion' looks like. In recent years, image-enhanced endoscopy has become common, but white-light endoscopy (WLI) is still the first step for detection and characterization of lesions in general clinical practice. Settings and practice of routine esophagogastroduodenoscopy (EGD) such as use of antispasmodics, number of endoscopic images taken, and observational procedure are customarily decided in each facility in each country and are not well standardized. Therefore, in the present article, we attempted to outline currently available evidence and actual Japanese practice on gastric cancer screening using WLI, and provide tips for detecting EGC during routine EGD which could become the basis of future research. PMID- 26836613 TI - Biosorption of lead from aqueous solutions by ion-imprinted tetraethylenepentamine modified chitosan beads. AB - In this paper, the bio-based ion-imprinted tetraethylenepentamine (TEPA) modified chitosan beads using Pb(II) as imprinted ions (Pb-ITMCB) were chemically synthesized, characterized and applied to selectively adsorb Pb(II) ions from aqueous solutions containing other metal ions, which has the same concentration as that of Pb(II) ions. Batch adsorption experiments were performed to evaluate the adsorption conditions, selectivity and reusability. FTIR, SEM and TEM technologies were used to elucidate the mechanism of Pb-ITMCB adsorbing Pb(II) ions. The results showed that the adsorption capacity of Pb-ITMCB for Pb(II) ions reached 259.68 mg/g at pH 6, 40 degrees C. The adsorption data could be fitted well with pseudo-second order kinetics model and Langmuir isotherm model. Compared with other metal cations, Pb(II) ions showed an overall affinity of being adsorbed by Pb-ITMCB. With the participation of active groups including NH2, NH and OH, the adsorption reaction took place both inside and on the surface of Pb-ITMCB. It indicated that Pb-ITMCB is a comparatively promising biosorbent for selective removal of Pb(II) ions from aqueous solutions. PMID- 26836614 TI - Characterization of a novel galactan produced by Weissella confusa KR780676 from an acidic fermented food. AB - An exopolysaccharide (EPS) producing strain PUFSTM055 isolated from Idli batter (an Indian traditional cereal-legume based fermented food) was identified as Weissella confusa KR780676. The strain was shown to produce 17.2g/L (dry weight) of EPS in 2% sucrose supplemented MRS broth and the EPS was characterized. HPTLC analysis confirmed the presence of galactose monomers, indicating the homopolysaccharide nature of EPS. Fourier-transform infrared spectroscopy and nuclear magnetic resonance analysis revealed that the EPS was found to be a novel linear galactan containing alpha-(1->6)-linked galactose units. Scanning electron microscopy of the EPS revealed the presence of porous and spongy starch-like granules. Topographical examination of EPS by atomic force microscopy revealed that the EPS formed densely packed mesh-like structure with irregular spherical lumps. The EPS also showed high thermal stability with a degradation temperature of 287.5 degrees C and melting point at 274.65 degrees C. EPS was semi crystalline with crystallinity index of 0.23 and showed 100% water solubility index. These characteristics of the EPS would make it a promising hydrocolloid for food industries as bio-thickeners, stabilizers and also as an encapsulating material for delivery of food bioactive compounds. This is the first study reporting the galactan compose of the EPS from lactic acid bacteria. PMID- 26836615 TI - Recent advances in Rosaceae gum exudates: From synthesis to food and non-food applications. AB - In recent years, great interest has been devoted to the development of new applications for natural gums. These molecules were used for a variety of purposes since they are chemically inert, non-toxic, less expensive, biodegradable and widely available. They represent one of the most abundant raw materials used not only in commercial food products, but also in cosmetic and pharmaceutical products. Plant gums take their advantages compared to other gums (e.g., from animal and microbial sources) mainly because of their acceptance by consumers. Despite of the well description given in literature for the features of plant gum exudates, there is a lack distinguishing the different families that are producing gums, and their potential applications. Among these gums, the ones produced by Rosaceae family (e.g., almond, apricot, cherry, peach, and plum plants) have been taking special attention. Thus, the aim of this review is to report the recent advances in Rosaceae gum exudates. An emphasis is given for the formation mechanisms of these gums, their chemical composition, functional properties and structures, beneficial properties, as well as their food/non-food applications. PMID- 26836617 TI - In vitro evaluation for apatite-forming ability of cellulose-based nanocomposite scaffolds for bone tissue engineering. AB - Research on synthetic bioactive bone graft materials has significantly expanded in the past decade. In this study, the nanocomposite scaffold of semi interpenetrating networks (semi-IPN) cellulose-graft-polyacrylamide/nano hydroxyapatite was synthesized through free radical polymerization. The scaffolds were fabricated by the freeze-drying technique. The prepared semi-IPN nanocomposite scaffolds were characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), and X-ray diffraction (XRD) analysis. In addition, the mechanical properties (i.e., elastic modulus and compressive strength) of the scaffolds were investigated. The SEM images showed that the pores of the scaffolds were interconnected, and their sizes ranged from 120 MUm to 190 MUm. Under optimum conditions, the prepared scaffolds had a compressive strength of 4.80 MPa, an elastic modulus of 0.29 GPa and a value of 47.37% porosity. Furthermore, the apatite-forming ability of the scaffolds was determined using simulated body fluid (SBF) for 28 days. The results revealed that the new apatite particles could grow on the surface of the scaffolds after a 14-day immersion in SBF. Finally, this study suggests that the prepared semi-IPN nanocomposites that closely mimic the properties of bone tissue could be a promising scaffold for bone tissue engineering. PMID- 26836616 TI - Characterization of an alkaline beta-agarase from Stenotrophomonas sp. NTa and the enzymatic hydrolysates. AB - An extracellular agarase from marine bacterium Stenotrophomonas sp. NTa was purified to homogeneity. By size exclusion chromatography and SDS-PAGE analysis, the enzyme was determined to be a homodimer with monomeric molecular mass of 89.0 kDa. The optimal temperature and pH of strain NTa agarase were 40 degrees C and 10.0, respectively. It exhibited striking stability across a wide pH range of 5.0 11.0. Agarase from Stenotrophomonas sp. NTa had a relatively good resistance against the detected inhibitors, detergents and urea denaturant. The Km and Vmax for agar were 11.3mg/ml and 25.4 U/mg, respectively. Thin layer chromatography analysis, mass spectrometry, and enzyme assay using p-nitrophenyl-alpha/beta-D galactopyranoside revealed that strain NTa agarase was a beta-agarase that degraded agarose into neoagarobiose, neoagarotetraose and neoagarohexaose as the predominant products, as well as a small amount of 3,6-anhydro-alpha-L-galactose. This is the first to present evidence of agarolytic activity in strain from genus Stenotrophomonas. PMID- 26836618 TI - Low intensity ultrasound increases the fermentation efficiency of Lactobacillus casei subsp.casei ATTC 39392. AB - L-Lactic acid (L-LA) is one of the microbial products with several applications and its production efficiency is so important. In the present study, we have been exploring application of low intensity ultrasound technology to improve the metabolic activity for L-lactic acid production by Lactobacillus casei in different mediums. L-LA, biomass production and substrate (protein) consumption were measured as parameters of fermentation yield. L-LA and protein contents were determined using the titratable acidity and the biuret method respectively. Spectrophotometry (OD600nm) was used for measuring cell growths. L-LA, biomass production and protein consumption considered as dependent variables, but the amplitude of waves (20%, 40% and 60%), waves duration (15, 30, 45 s) and add of peptone (2, 6 and 10 g/l) as independent variables. The results showed that L-LA, biomass production and substrate consumption significantly increased (~25%). Optimum conditions for biomass production was amplitude of 60%, 15s exposure time and 10 g/l peptone, while for acid lactic production and substrate consumption was 40%, 30s and 6g/l peptone, respectively. Flowcytometry analysis also showed that sonication led to increasing cell membrane permeability. This observation shows low intensity ultrasound as a potential parameter in the improvement of metabolic activity of L. casei. PMID- 26836619 TI - In vitro evaluation of antioxidant and cytotoxic activities of lignin fractions extracted from Acacia nilotica. AB - Lignin is one of the most important phytomacromolecule with diverse therapeutic properties such as anticancer, antimicrobial, anti-inflammatory and immune stimulatory. The present study was carried out to evaluate the in vitro antioxidant, free radical scavenging and anti-proliferative/cytotoxic activities of eleven different lignin fractions, extracted from the wood of Acacia nilotica by pressurized solvent extraction (PSE) and successive solvent extraction (SSE) methods. Results indicate that the PSE fractions have high polyphenolic content and reducing power. However, the antioxidant efficiency examined by DPPH and ABTS radical scavenging assay was higher in SSE fractions. All lignin fractions revealed a significant ability to scavenge nitric oxide, hydroxyl and superoxide radicals. The extracted lignin fractions display high ferric ion reducing capacity and also possess excellent antioxidant potential in the hydrophobic (linoleic acid) system. Fractions extracted by polar solvent has the highest iron (Fe(2+)) chelating activity as compared to other factions, indicating their effect on the redox cycling of iron. Four lignin fractions depicted higher cytotoxic potential (IC50: 2-15 MUg/mL) towards breast cancer cell line (MCF-7) but were ineffective (IC50: >= 100 MUg/mL) against normal primary human hepatic stellate cells (HHSteCs). These findings suggest that the lignin extracts of A. nilotica wood has a remarkable potential to prevent disease caused by the overproduction of radicals and also seem to be a promising candidate as natural antioxidant and anti-cancer agents. PMID- 26836620 TI - Removal and separation of Cu(II) from aqueous solutions using nano-silver chitosan/polyacrylamide membranes. AB - In the present study, adsorption of Cu(II) ions from aqueous solutions was evaluated using new thin adsorptive membranes modified with silver nanoparticles. Membranes were prepared from chitosan/polyacrylamide polymer blend. The variation of adsorption process was investigated in batch sorption mode. Infrared absorption spectra were applied for chemical characterization of the prepared polymer blend. Thermogravimetric analysis showed that addition of polyacrylamide to chitosan increased its thermal stability. The kinetics and thermodynamic parameters of Cu(II) ions adsorption onto the membranes were studied by removal experiments of Cu(II) ions from standard aqueous solutions. The kinetic data fitted to the traditional Lagergren adsorption kinetic equations. Thermodynamic studies indicated endothermic (DeltaH degrees > 0) and spontaneous (DeltaG degrees < 0) adsorption together with entropy generation (DeltaS degrees > 0) at the solid/liquid interface process. Regeneration experiments showed that the newly prepared membranes could be reconditioned without significant loss of its initial properties even after three adsorption-desorption cycles. The results suggest that the prepared composite membranes can be efficiently applied for the adsorptive removal of Cu(II) ions from natural water samples. Antimicrobial activity was tested against two gram negatives, two gram positives and Candida sp. microbes and they showed a remarkable bioactivity indicating the capability of applying such membranes for a dual action. PMID- 26836621 TI - Eye-tracking reveals a slowdown of social context processing during intention attribution in patients with schizophrenia. AB - BACKGROUND: Schizophrenia is associated with poor theory of mind (ToM), particularly in the attribution of intentions to others. It is also associated with abnormal gaze behaviours and contextual processing. This study investigated to what extent impaired ToM in patients with schizophrenia is related to abnormal processing of social context. METHODS: We evaluated ToM using a nonverbal intention attribution task based on comic strips depicting social/nonsocial and contextual/noncontextual events while eye movements were recorded. Eye-tracking was used to assess processing time dedicated to visual cues contained in regions of interest identified in a pilot study. We measured cognitive contextual control on a separate task. RESULTS: We tested 29 patients with schizophrenia and 29 controls. Compared with controls, patients were slower in intention attribution but not in physical reasoning. They looked longer than controls at contextual cues displayed in the first 2 context pictures of the comic strips, and this difference was greater for intention attribution than for physical reasoning. We found no group difference in time spent looking at noncontextual cues. Patients' impairment in contextual control did not explain their increased reaction time and gaze duration on contextual cues during intention attribution. LIMITATIONS: Difficulty may not have been equivalent between intention attribution and physical reasoning conditions. CONCLUSION: Overall, schizophrenia was characterized by a delay in intention attribution related to a slowdown of social context processing that was not explained by worse executive contextual control. PMID- 26836624 TI - Rhinovirus-induced asthma exacerbations and risk populations. AB - PURPOSE OF REVIEW: This article discusses recent findings into the mechanisms that determine how viruses trigger asthma exacerbations. RECENT FINDINGS: Substantial progress has been made in our understanding of the pathogenesis of virus-induced asthma exacerbations. This includes new insights into the role of bacteria, the regulation of interferon responses, and the discovery of innate immune pathways that link viral infections with allergic inflammation. Progress has also been made in elucidating the genetic risk factors for asthma exacerbations, most notably the contribution of the ORMDL3/GSDMB locus on 17q, the mechanisms underlying the farming effect, and the discovery that CDHR3 binds to rhinovirus species C. SUMMARY: Asthma exacerbations are heterogeneous conditions that involve the complex interplay between environmental exposures and innate and adaptive immune function in genetically predisposed individuals. Recent insights into the interrelationships between these factors provide new opportunities for therapeutic intervention. PMID- 26836622 TI - Aberrant network connectivity during error processing in patients with schizophrenia. AB - BACKGROUND: Neuroimaging methods have pointed to deficits in the interaction of large-scale brain networks in patients with schizophrenia. Abnormal connectivity of the right anterior insula (AI), a central hub of the salience network, is frequently reported and may underlie patients' deficits in adaptive salience processing and cognitive control. While most previous studies used resting state approaches, we examined right AI interactions in a task-based fMRI study. METHODS: Patients with schizophrenia and healthy controls performed an adaptive version of the Eriksen Flanker task that was specifically designed to ensure a comparable number of errors between groups. RESULTS: We included 27 patients with schizophrenia and 27 healthy controls in our study. The between-groups comparison replicated the classic finding of reduced activation in the midcingulate cortex (MCC) in patients with schizophrenia during the commission of errors while controlling for confounding factors, such as task performance and error frequency, which have been neglected in many previous studies. Subsequent psychophysiological interaction analysis revealed aberrant functional connectivity (FC) between the right AI and regions in the inferior frontal gyrus and temporoparietal junction. Additionally, FC between the MCC and the dorsolateral prefrontal cortex was reduced. LIMITATIONS: As we examined a sample of medicated patients, effects of antipsychotic medication may have influenced our results. CONCLUSION: Overall, it appears that schizophrenia is associated with impairment of networks associated with detection of errors, refocusing of attention, superordinate guiding of cognitive control and their respective coordination. PMID- 26836623 TI - Prediction error and somatosensory insula activation in women recovered from anorexia nervosa. AB - BACKGROUND: Previous research in patients with anorexia nervosa showed heightened brain response during a taste reward conditioning task and heightened sensitivity to rewarding and punishing stimuli. Here we tested the hypothesis that individuals recovered from anorexia nervosa would also experience greater brain activation during this task as well as higher sensitivity to salient stimuli than controls. METHODS: Women recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm. RESULTS: Twenty-four women recovered from anorexia nervosa (mean age 30.3 +/- 8.1 yr) and 24 control women (mean age 27.4 +/- 6.3 yr) took part in this study. The recovered anorexia nervosa group showed greater left posterior insula activation for the prediction error model analysis than the control group (family-wise error- and small volume-corrected p < 0.05). A group * condition analysis found greater posterior insula response in women recovered from anorexia nervosa than controls for unexpected stimulus omission, but not for unexpected receipt. Sensitivity to punishment was elevated in women recovered from anorexia nervosa. LIMITATIONS: This was a cross-sectional study, and the sample size was modest. CONCLUSION: Anorexia nervosa after recovery is associated with heightened prediction error-related brain response in the posterior insula as well as greater response to unexpected reward stimulus omission. This finding, together with behaviourally increased sensitivity to punishment, could indicate that individuals recovered from anorexia nervosa are particularly responsive to punishment. The posterior insula processes somatosensory stimuli, including unexpected bodily states, and greater response could indicate altered perception or integration of unexpected or maybe unwanted bodily feelings. Whether those findings develop during the ill state or whether they are biological traits requires further study. PMID- 26836625 TI - Comparison Between Minimally Invasive and Open Pancreaticoduodenectomy: A Systematic Review. AB - INTRODUCTION: Minimally invasive approaches (laparoscopic or robotic) are used in various operations. Our aim was to compare them with the open approach in pancreaticoduodenectomy. METHODS: We conducted a search for articles published in MEDLINE database comparing minimally invasive (laparoscopic or robotic) with open pancreaticoduodenectomy on June 15, 2014. RESULTS: Our search yielded 136 articles. We excluded 122 articles and we took into consideration 14 (10 for laparoscopic and 4 for robotic pancreaticoduodenectomies). Most cases were related to malignant diseases and tumors treated with minimally invasive operations tended to be smaller. There were relatively high conversion rates in both laparoscopic (0% to 15%) and robotic procedures (4.5% to 10%). There were no significant differences regarding resection margins, rates of pancreatic fistula formation, bile leak, and delayed gastric emptying, reoperation rates, and intraoperative and postoperative mortality. On the contrary, blood loss was less in minimally invasive than open operations, although this difference was not always significant. Moreover, totally laparoscopic and robotic procedures lasted longer than the open ones, whereas hand-assisted laparoscopic procedures did not. However, the findings regarding the number of the retrieved lymph nodes, the length of hospital stay, and costs were inconclusive and controversial. CONCLUSIONS: Laparoscopic and robotic pancreaticoduodenectomy are feasible, safe, and oncologically equivalent alternatives to open pancreaticoduodenectomy. Minimally invasive operations have the advantage of the less blood loss, but totally laparoscopic and robotic procedures last longer than open procedures. PMID- 26836626 TI - Safety and Efficacy of a New Bipolar Energy Device for Parenchymal Dissection in Laparoscopic Liver Resection. AB - BACKGROUND: Despite emerging technologies, parenchymal transection still remains challenging in liver resection. The aim of this study is to assess the safety and efficacy of a new articulating vessel sealer for laparoscopic hepatectomy. Our hypothesis was that this new device would facilitate parenchymal transection and reduce intraoperative costs in laparoscopic hepatectomy. METHODS: Within 18 months, a 5 cm bipolar articulating vessel sealer was used in 32 laparoscopic liver resections (LLR). By excluding 4 patients who underwent concomitant colorectal resections, the outcomes of the remaining 28 patients (group 1) were compared with 28 patients who underwent LLR by the same surgical group using other energy devices (group 2). RESULTS: Tumor type was malignant in 71% of patients (n=20) in group 1 and 89% of the patients (n=25) in group 2 (P=0.360). The number and size of tumors were similar in both groups, as well as the type of resections performed. In group 1, there was a less number of adjunctive devices (ie, energy, clip appliers, staplers) used (median 2) compared with group 2 (median 3, P=0.032). Parenchymal transection time (mean+/-SEM 28.2+/-3.5 vs. 55.2+/-4.1 min, respectively, P<0.001) and total operative time (200.1+/-13.7 vs. 242.7+/-14.4 min, respectively, P=0.036) were shorter for group 1 versus group 2. Estimated blood loss, transfusion rate, margin status, and length of stay were similar between the groups. There was no mortality. Morbidity was 11% (n=3) in group 1 and 18% (n=5) in group 2 (P=NS). The overall intraoperative costs were an average of $3000 less in group 1 (95% confidence interval, $1090-$4930, P=0.0029) compared with group 2. CONCLUSIONS: This study demonstrates the safety and efficacy of a new energy device for LLR. Our experience suggested that this new device provided the functionality of both a vessel sealer and a stapler with its large jaw and articulation. PMID- 26836627 TI - One-year Surgical Outcomes and Costs for Medicaid Versus Non-Medicaid Patients Undergoing Laparoscopic Roux-en-Y Gastric Bypass: A Single-Center Study. AB - PURPOSE: To compare 1-year outcomes and costs between severely obese Medicaid and non-Medicaid patients who underwent laparoscopic Roux-en-Y gastric bypass surgery. METHODS: This is a single-institution retrospective review comparing 33 Medicaid patients to 99 randomly selected non-Medicaid patients (1:3 case control). Ninety-day and 1-year outcomes were extracted from the electronic health record. Costs were obtained from the UW information technology division. Bivariate analyses were used to compare study variables. RESULTS: Emergency department visits (48.2% vs. 27.4%; P=0.06) and readmissions (37.0% vs. 14.7%; P=0.01) were more common for Medicaid patients. Medicaid patients had less excess body weight loss (50.7% vs. 65.6%; P=0.001) but similar comorbidity resolution and complication rates. One-year median costs were similar between Medicaid and non-Medicaid patients ($21,160 vs. $24,215; P=0.92). CONCLUSIONS: One-year comorbidity resolution, complications, and costs following laparoscopic Roux-en-Y gastric bypass were similar between Medicaid and non-Medicaid patients. Focusing on reducing emergency department presentations and readmissions would be a high impact area for future quality improvement initiatives. PMID- 26836628 TI - Robotic Liver Surgery: Early Experience From a Single Surgical Center. AB - INTRODUCTION: The use of robotic surgery in liver resection is still limited. Our aim is to present our early experience of robotic liver resection. MATERIALS AND METHODS: It is a retrospective review of Sanchinarro University hospital experience of robotic liver resection performed from 2011 to 2014. Clinicopathologic characteristics, and perioperative and postoperative outcomes were recorded and analyzed. RESULTS: Twenty-one procedures have been performed and 13 (65%) of them were for malignancy. There were 2 left hepatectomies, 1 right hepatectomy, 1 associated liver partition and portal vein ligation staged procedure (both steps by robotic approach), 1 bisegmentectomy and 3 segmentectomies, 9 wedge resections, and 3 pericystectomies. The mean operating time was 282 minutes (range, 90 to 540 min). Overall conversion rate and postoperative complication rate were 4.7% and 19%, respectively. The mean length of hospital stay was 13.4 days (range, 4 to 64 d). CONCLUSION: From our early experience, robotic liver surgery is a safe and feasible procedure, especially for major hepatectomies. PMID- 26836629 TI - Feasibility of simultaneous 18F-FDG PET/MRI for the quantitative volumetric and metabolic measurements of abdominal fat tissues using fat segmentation. AB - BACKGROUND: Quantification of volume and inflammatory activity in the fat tissue is important because these are closely related to type 2 diabetes mellitus and cardiovascular disease. Fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) has been utilized to measure the metabolic activity of fat tissue. In this study, we assessed the feasibility of simultaneous PET/magnetic resonance (MR) in metabolic and volumetric measurements of fat tissue and the potential advantage over PET/CT. METHODS: Twenty-four healthy individuals were enrolled, who underwent simultaneous F-FDG PET/MRI. Twenty-five F-FDG PET/CT scans were selected. Isocontour volumes of interest (VOIs) were used to segment and separate visceral fat (VF) and abdominal subcutaneous fat (SF) in using the MR image (T1 DIXON VIBE sequence) of PET/MR and the CT image of PET/CT. Volume, mean standardized uptake value of VF, and SF VOIs were calculated. RESULTS: Overlap between F-FDG PET and VF VOI was better in F-FDG PET/MR than PET/CT. The mean standardized uptake value of VF was associated with the degree of intestinal uptake on F-FDG PET/CT, but not on F-FDG PET/MR. Volumetric and metabolic measurements using F-FDG PET/MR showed an excellent reproducibility, with a high intraclass correlation coefficient between different observers (0.951-0.997). The measured metabolic activity was higher in VF than SF. CONCLUSION: We established a method for the quantitative measurement of volume and metabolic status of abdominal VF and SF using simultaneous F-FDG PET/MR. F-FDG PET/MR has an advantage over F-FDG PET/CT in terms of being less confounded by intestinal uptake. This method could be used to assess the inflammatory activity of fat tissue, which is a major risk factor for type 2 diabetes mellitus and cardiovascular disease. PMID- 26836630 TI - Prevalence of sensitization to 'improver' enzymes in UK supermarket bakers. AB - BACKGROUND: Supermarket bakers are exposed not only to flour and alpha-amylase but also to other 'improver' enzymes, the nature of which is usually shrouded by commercial sensitivity. We aimed to determine the prevalence of sensitization to 'improver' enzymes in UK supermarket bakers. METHODS: We examined the prevalence of sensitization to enzymes in 300 bakers, employed by one of two large supermarket bakeries, who had declared work-related respiratory symptoms during routine health surveillance. Sensitization was determined using radioallergosorbent assay to eight individual enzymes contained in the specific 'improver' mix used by each supermarket. RESULTS: The prevalence of sensitization to 'improver' enzymes ranged from 5% to 15%. Sensitization was far more likely if the baker was sensitized also to either flour or alpha-amylase. The prevalence of sensitization to an 'improver' enzyme did not appear to be related to the concentration of that enzyme in the mix. CONCLUSIONS: We report substantial rates of sensitization to enzymes other than alpha-amylase in UK supermarket bakers; in only a small proportion of bakers was there evidence of sensitization to 'improver mix' enzymes without sensitization to either alpha-amylase or flour. The clinical significance of these findings needs further investigation, but our findings indicate that specific sensitization in symptomatic bakers may not be identified without consideration of a wide range of workplace antigens. PMID- 26836632 TI - Diagnosis of Pyruvate Kinase Deficiency. PMID- 26836633 TI - Correction to Letter: Fluorinated Aromatic Amino Acids Are Sensitive (19)F NMR Probes for Bromodomain-Ligand Interactions. PMID- 26836631 TI - Genome assembly and geospatial phylogenomics of the bed bug Cimex lectularius. AB - The common bed bug (Cimex lectularius) has been a persistent pest of humans for thousands of years, yet the genetic basis of the bed bug's basic biology and adaptation to dense human environments is largely unknown. Here we report the assembly, annotation and phylogenetic mapping of the 697.9-Mb Cimex lectularius genome, with an N50 of 971 kb, using both long and short read technologies. A RNA seq time course across all five developmental stages and male and female adults generated 36,985 coding and noncoding gene models. The most pronounced change in gene expression during the life cycle occurs after feeding on human blood and included genes from the Wolbachia endosymbiont, which shows a simultaneous and coordinated host/commensal response to haematophagous activity. These data provide a rich genetic resource for mapping activity and density of C. lectularius across human hosts and cities, which can help track, manage and control bed bug infestations. PMID- 26836634 TI - The Effects of Amnestic Mild Cognitive Impairment on Go/NoGo Semantic Categorization Task Performance and Event-Related Potentials. AB - We examined the effects of amnestic mild cognitive impairment (aMCI) on behavioral (response times and error rates) and scalp-recorded event-related potential (ERP) measures of response execution and inhibition, using Go/NoGo tasks involving basic and superordinate semantic categorization. Twenty-five aMCI (16 F; 68.5+/-8 years) and 25 age- and gender-matched normal control subjects (16 F; 65.4+/-7.1 years) completed two visual Go/NoGo tasks. In the single car task, responses were made based on single exemplars of a car (Go) and a dog (NoGo) (basic). In the object animal task, responses were based on multiple exemplars of objects (Go) and animals (NoGo) (superordinate). The aMCI subjects had higher commission errors on the NoGo trials compared to the control subjects, whereas both groups had comparable omission errors and reaction times during the Go trials. The aMCI subjects had significantly prolonged N2 ERP latency during Go and NoGo trials across tasks compared to the controls. Both groups showed similar categorization effects and response type effects in N2/P3 ERP latencies and P3 amplitude. Our findings indicate that altered early neural processing indexed by N2 latency distinguishes subjects with aMCI from controls during the Go/NoGo task. Prolonged Go-N2 latency in aMCI appears to precede behavioral changes in response execution, whereas prolonged NoGo-N2 latency underlies behavioral deterioration in response inhibition. PMID- 26836635 TI - Different Patterns of Correlation between Grey and White Matter Integrity Account for Behavioral and Psychological Symptoms in Alzheimer's Disease. AB - Behavioral disorders and psychological symptoms (BPSD) in Alzheimer's disease (AD) are known to correlate with grey matter (GM) atrophy and, as shown recently, also with white matter (WM) damage. WM damage and its relationship with GM atrophy are reported in AD, reinforcing the interpretation of the AD pathology in light of a disconnection syndrome. It remains uncertain whether this disconnection might account also for different BPSD observable in AD. Here, we tested the hypothesis of different patterns of association between WM damage of the corpus callosum (CC) and GM atrophy in AD patients exhibiting one of the following BPSD clusters: Mood (i.e., anxiety and depression; ADmood), Frontal (i.e., dishinibition and elation; ADfrontal), and Psychotic (delusions and hallucinations; ADpsychotic) related symptoms, as well as AD patients without BPSD. Overall, this study brings to light the strict relationship between WM alterations in different parts of the CC and GM atrophy in AD patients exhibiting BPSD, supporting the hypothesis that such symptoms are likely to be caused by characteristic patterns of neurodegeneration of WM and GM, rather than being a reactive response to accumulation of cognitive disabilities, and should therefore be regarded as potential markers of diagnostic and prognostic value in AD. PMID- 26836637 TI - Azide Binding Controlled by Steric Interactions in Second Sphere. Synthesis, Crystal Structure, and Magnetic Properties of [Ni(II)2(L)(MU(1,1)-N3)][ClO4] (L = Macrocyclic N6S2 Ligand). AB - The dinuclear Ni(II) complex [Ni2(L(2))][ClO4]2 (3) supported by the 28-membered hexaaza-dithiophenolate macrocycle (L(2))(2-) binds the N3(-) ion specifically end-on yielding [Ni2(L(2))(MU(1,1)-N3)][ClO4] (7) or [Ni2(L(2))(MU(1,1) N3)][BPh4] (8), while the previously reported complex [Ni2L(1)(MU(1,3)-N3)][ClO4] (2) of the 24-membered macrocycle (L(1))(2-) coordinates it in the end-to-end fashion. A comparison of the X-ray structures of 2, 3, and 7 reveals the form selective binding of complex 3 to be a consequence of its preorganized, channel like binding pocket, which accommodates the azide anion via repulsive CH...pi interactions in the end-on mode. In contrast to [Ni2L(1)(MU(1,3)-N3)][ClO4] (2), which features a S = 0 ground state, [Ni2(L(2))(MU(1,1)-N3)][BPh4] (8) has a S = 2 ground state that is attained by competing antiferromagnetic and ferromagnetic exchange interactions via the thiolato and azido bridges with a value for the magnetic exchange coupling constant J of 13 cm(-1) (H = -2JS1S2). These results are further substantiated by density functional theory calculations. The stability of the azido-bridged complex determined by isothermal titration calorimetry in MeCN/MeOH 1/1 v/v (log K11 = 4.88(4) at I = 0.1 M) lies in between those of the fluorido- (log K11 = 6.84(7)) and chlorido-bridged complexes (log K11 = 3.52(5)). These values were found to compare favorably well with the equilibrium constants derived at lower ionic strength (I = 0.01 M) by absorption spectrophotometry (log K11 = 5.20(1), 7.77(9), and 4.13(3) for N3(-), F(-), and Cl(-) respectively). PMID- 26836639 TI - Safety-Related Concerns of Parents for Children with Disabilities and Chronic Conditions. AB - OBJECTIVE: The aim of this study was to explore the safety-related concerns of parents of children with a variety of disabilities and chronic conditions. We sought to examine concerns common to parents as they related to their children's delayed development, behavioral difficulties, and chronic conditions. METHOD: A qualitative approach guided by grounded theory was used. Participants included parents of children between 1 and 5 years with a disability or chronic condition who resided in British Columbia, Canada. Data were collected using in-depth in person interviews and analysis conducted using constant comparative methods. RESULTS: Three themes were identified that reflected parental safety concerns. These included concerns about: (1) Child's level of understanding about danger; (2) Child interactions with physical environment (concerns about child movement, concerns about ingestions); (3) Child interactions with social environment. Difficult-to-manage behaviors and cognitive limitations exacerbated parents' safety concerns. Parents were found to share safety concerns about movement and ingestions across a range of types of child health conditions. CONCLUSION: For themes of child movement and child ingestions, findings supported the utility of a noncategorical approach for the design of injury prevention strategies for these types of concerns. Parent concerns about child lack of understanding about risk and social safety concerns were linked to a smaller number of conditions and supported a more tailored approach. Flexible approaches may be needed that can offer both generic and specific information and to meet the needs of parents and clinicians. PMID- 26836640 TI - Validation of the Behavioral Health Checklist in Diverse Pediatric Primary Care Settings. AB - OBJECTIVE: Examine the validity and clinical utility of the Behavioral Health Checklist (BHCL), a screening tool with 2 forms (4-7, 8-12 years) developed for use with children of diverse backgrounds. METHOD: At pediatric primary care appointments, the parents of 1274 children completed a demographic form, the BHCL, and the Child Behavior Checklist (CBCL). Concurrent validity was examined by conducting correlations between the BHCL and the diagnostic scales of the CBCL. Diagnostic prediction was examined by conducting logistic regression analyses and plotting receiver operating characteristics (ROC) curves. Clinical utility was investigated by examining sensitivity, specificity, and kappa corrections for total predictive power. RESULTS: The pattern of correlations with the CBCL provided evidence of convergent and discriminant validity for both versions of the BHCL. ROC curve plots provided clear evidence of predictive validity (area under curve values ranged from .84 to .96 across factors and both age-determined versions). Cut-points achieving sensitivity and specificity values of at least .70 were identified for each BHCL factor for each version. CONCLUSION: The BHCL was demonstrated to have strong construct and predictive validity. The predictive validity of each version was demonstrated across genders, socioeconomic status, and racial groups (black or African American and white). The BHCL has promise as a developmentally and culturally effective behavioral health screener for use in pediatric primary care practices. PMID- 26836638 TI - Identifying Maternal Depression in Pediatric Primary Care: Changes Over a Decade. AB - OBJECTIVE: Maternal depression affects 10% to 40% of mothers with young children and has negative consequences for children's health and development. The American Academy of Pediatrics (AAP) recommends that pediatricians identify women with maternal depression. The authors examined trends in inquiring about (asking informal questions) or screening for (using a standardized instrument) maternal depression by pediatricians in 2004 and 2013 and identified correlates of usually inquiring/screening to identify maternal depression. METHODS: Data were ascertained from 778 nontrainee pediatricians exclusively practicing general pediatrics who completed the 2004 (n = 457) and 2013 (n = 321) AAP Periodic Surveys. Pediatricians answered questions about physician and practice characteristics, training, attitudes, and inquiring/screening to identify maternal depression. Sample weights were used to reduce nonresponse bias. Weighted descriptive and logistic regression analyses were conducted. RESULTS: The prevalence of usually inquiring/screening to identify maternal depression increased from 33% to 44% (p < .01). In both years, pediatricians who usually inquired about child/adolescent depression had increased odds of usually inquiring/screening to identify maternal depression. Patient race/ethnicity and training in adult Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for depression were associated with inquiring/screening in 2004, and believing that family screening is within the scope of the pediatrician was associated with inquiring/screening in 2013. CONCLUSION: Although inquiring/screening about maternal depression has increased since 2004, less than half of pediatricians usually screen or inquire about maternal depression, representing a missed opportunity to identify depression and manage or refer women for treatment. Further training on the importance of mental and family health to children's health may increase identification of maternal depression in pediatric primary care. PMID- 26836641 TI - Children with Special Health Care Needs, Supplemental Security Income, and Food Insecurity. AB - OBJECTIVES: To assess food insecurity in low-income households with young children with/without special health care needs (SHCN) and evaluate relationships between child Supplemental Security Income (SSI) receipt and food insecurity. METHODS: A cross-sectional survey (2013-2015) of caregivers was conducted at 5 medical centers. Eligibility included index child age <48 months without private health insurance and a caregiver fluent in English or Spanish. Interviews included sociodemographics, 5-item Children with Special Health Care Needs Screener, 18-item US Food Security Survey Module, household public assistance program participation, and child SSI receipt. Household and child food insecurity, each, were evaluated using multivariable logistic regression models. RESULTS: Of 6724 index children, 81.5% screened negative for SHCN, 14.8% positive for SHCN (no SSI), and 3.7% had SHCN and received SSI. After covariate control, households, with versus without a child with SHCN, were more likely to experience household (Adjusted odds ratios [AOR] 1.24, 95% confidence intervals [CI], 1.03 1.48) and child (AOR 1.35, 95% CI, 1.11-1.63) food insecurity. Among households with children with SHCN, those with children receiving, versus not receiving SSI, were more likely to report household (AOR 1.42, 95% CI, 0.97-2.09) but not child food insecurity. CONCLUSION: Low-income households with young children having SHCN are at risk for food insecurity, regardless of child SSI receipt and household participation in other public assistance programs. Policy recommendations include reevaluation of assistance programs' income and medical deduction criteria for households with children with SHCN to decrease the food insecurity risk faced by these children and their families. PMID- 26836642 TI - Experience with Gambling in Late Childhood and Early Adolescence: Implications for Substance Experimentation Behavior. AB - OBJECTIVE: Previous research among late adolescents suggests an additive association between levels of engagement in gambling and vulnerability to substance use disorder. The aim of our research was to investigate the frequency of gambling experience in childhood and early adolescence and to examine the association between alcohol/cigarette/energy drink consumption and gambling in this young population. METHODS: A survey called "Pinocchio" was conducted during the 2013 to 2014 school year at primary and secondary schools in Padua (north eastern Italy) on a sample of 1325 students in sixth to eighth grade (11-13 year olds). Multilevel analysis, taking the school-level variance into account, established an adjusted association between gambling and attitude to risk-taking among early adolescents. RESULTS: Among eighth graders, 45.8% of the boys and 35.4% of the girls reported at least 1 type of gambling. In a fully-adjusted model, having experience of gambling confers a higher likelihood of being consumers (at least once a month) of other substances (alcohol, cigarettes, energy drinks, or marijuana). CONCLUSION: Gambling behavior is widespread among adolescents. An association with other risk-taking behavior was found in this study, and this provides further evidence of the need for a greater awareness of gambling behavior in early adolescence. PMID- 26836643 TI - Postpartum Depression Screening by Pediatricians: Time to Close the Gap. PMID- 26836644 TI - Behavioral Management of Sleep Problems in Infants Under 6 Months--What Works? AB - OBJECTIVE: Crying and unsettled behavior in infancy is common. Prolonged disturbed infant sleep can have significant negative effects on the development of the child, and on the psychological well-being of the mother. Compared to studies examining the effects of behavioral sleep programs such as extinction based techniques in infants over 6 months of age, fewer studies have looked at such strategies in infants under 6 months of age. The aim of this article is to summarize the literature examining the effects of behavioral techniques on infant sleep outcomes in the first 6 months of life and provide evidence based recommendations for the management of infant sleep disturbance. METHOD: An electronic search of the literature was performed to identify studies which examined the effects of a behavioral intervention aimed at improving sleep in infants under 6 months of age. RESULTS: Eleven studies were identified, of which 8 demonstrated improvements in infant sleep outcomes subsequent to the implementation of an educational behavioral program. CONCLUSION: Education directed to parents about the use of simple, prescriptive, behavioral techniques is effective in improving infant sleep. Long term follow-up studies have failed to find any negative effects on the child, either from a psychological or physical perspective. PMID- 26836645 TI - It's All About the Terminology: Term Infants and Postterm Infants. PMID- 26836646 TI - Authors' Response: Preterm and Postterm Births: Terminology and Definitions. PMID- 26836647 TI - Multi-slice imAGe generation using intra-slice paraLLel imaging and Inter-slice shifting (MAGGULLI). AB - For acceleration of imaging time, multi-band imaging techniques (e.g. CAIPIRINHA) use the sensitivity differences of the multi-channel RF coils in the slice selection direction. To more effectively utilize the RF coil characteristics than the conventional multi-band imaging techniques, we propose a new imaging technique, called multi-slice image generation using intra-slice parallel imaging and inter-slice shifting (MAGGULLI). The proposed technique used an inter-slice shifting gradient in slice selection direction to make multi-slice images shift in the frequency encoding direction. Thus, aliasing caused by sub-sampling in the phase encoding direction is orthogonal to that by multi-band imaging with the inter-slice shifting, both of which are resolved by using the sensitivity information of the RF coil. Phantom and in vivo imaging experiments for the acceleration factors up to 10 demonstrate that the quality of the images reconstructed by MAGGULLI are better than that of CAIPIRINHA for high acceleration factors in the qualitative and quantitative analysis. PMID- 26836648 TI - Enzyme-free and label-free ultra-sensitive colorimetric detection of Pb(2+) using molecular beacon and DNAzyme based amplification strategy. AB - An enzyme-free and label-free colorimetric Pb(2+) sensor based on DNAzyme and molecular beacon (MB) has been developed and demonstrated by recycle using enzyme strand for signal amplification. The substrate strand DNA (S-DNA) of DNAzyme could be converted into MB structure with base pairs of stem part at the both ends. The MB could hybridize with enzyme strand DNA (E-DNA) to form DNAzyme, and be activated and cleaved in the presence of Pb(2+). The cleaved MB is much less stable, releasing from the DNAzyme as two product pieces. The product pieces of MB are flexible and could bind to unmodified AuNPs to effectively stabilize them against salt-induced aggregation. Then, the E-DNA is liberated to catalyze the next reaction and amplify the response signal. By taking advantage of repeated using of E-DNA, our proposed method exhibited high sensitive for Pb(2+) detection in a linear range from 0.05 to 5 nM with detection limit of 20 pM by UV-vis spectrometer. Moreover, this method was also used for determination of Pb(2+) in river water samples with satisfying results. Importantly, this strategy could reach high sensitivity without any modification and complex enzymatic or hairpins based amplification procedures. PMID- 26836649 TI - Label-free impedimetric biosensor for Salmonella Typhimurium detection based on poly [pyrrole-co-3-carboxyl-pyrrole] copolymer supported aptamer. AB - The Gram-negative bacterium, Salmonella Typhimurium (S. Typhimurium) is a food borne pathogen responsible for numerous hospitalisations and deaths all over the world. Conventional detection methods for pathogens are time consuming and labour intensive. Hence, there is considerable interest in faster and simpler detection methods. Polypyrrole-based polymers, due to their intrinsic chemical and electrical properties, have been demonstrated to be valuable candidates for the fabrication of chemo/biosensors and functional surfaces. Similarly aptamers have been shown to be good alternatives to antibodies in the development of affinity biosensors. In this study, we report on the combination of poly [pyrrole-co-3 carboxyl-pyrrole] copolymer and aptamer for the development of a label-less electrochemical biosensor suitable for the detection of S. Typhimurium. Impedimetric measurements were facilitated by the effect of the aptamer/target interaction on the intrinsic conjugation of the poly [pyrrole-co-3-carboxyl pyrrole] copolymer and subsequently on its electrical properties. The aptasensor detected S. Typhimurium in the concentration range 10(2)-10(8) CFU mL(-1) with high selectivity over other model pathogens and with a limit of quantification (LOQ) of 100 CFU mL(-1) and a limit of detection (LOD) of 3 CFU mL(-1). The suitability of the aptasensor for real sample detection was demonstrated via recovery studies performed in spiked apple juice samples. We envisage this to be a viable approach for the inexpensive and rapid detection of pathogens in food, and possibly in other environmental samples. PMID- 26836651 TI - Homogeneous Immunosensor Based on Luminescence Resonance Energy Transfer for Glycated Hemoglobin Detection Using Upconversion Nanoparticles. AB - We report an immunosensor based on luminescence resonance energy transfer (LRET) to detect homogeneous glycated hemoglobin (HbA1c). This system uses near-infrared (NIR)-to-visible rare-earth upconversion nanoparticles (UCNPs), such as NaYF4:Yb(3+), Er(3+), as the donor and HbA1c as the acceptor. The HbA1c used as target molecules showed absorption at 541 nm, which corresponded with the emission of the UCNPs. When HbA1c was added, LRET occurred between the donor and acceptor under laser irradiation of 980 nm because of the specific recognition between the anti-HbA1c monocolonal antibody-functionalized UCNPs and HbA1c. In the absence of HbA1c, there was strong upconversion luminescence intensity; however, in its presence, the distance between the donor and acceptor decreased to enable energy transfer, consequently quenching the luminescence of the UCNPs. The proposed method was successfully applied to HbA1c detection in blood samples. Our results indicate that the LRET-based immunosensor allows for specific and sensitive detection of HbA1c in a homogeneous manner. PMID- 26836650 TI - Biochar-Facilitated Microbial Reduction of Hematite. AB - As an important component of soil organic matter (SOM), the transformation of pyrogenic carbon plays a critical role in the biogeochemical cycles of carbon and other redox-active elements such as iron (Fe). Herein, we studied the influences of wheat straw-derived biochars on the microbial reduction of 100 mM of hematite by the dissimilatory metal reducing bacteria Shewanella oneidensis MR-1 under anoxic conditions. The long-term microbial reduction extent and initial reduction rate of hematite were accelerated by more than 2-fold in the presence of 10 mg L( 1) biochar. Soluble leachate from 10 mg L(-1) biochar enhanced Fe(III) reduction to a similar degree. Microbially prereduced biochar leachate abiotically reduced hematite, consistent with the apparent electron shuttling capacity of biochar leachate. Electron paramagnetic resonance (EPR) analysis suggested that biochar leachate-associated semiquinone functional groups were likely involved in the redox reactions. In addition to electron shuttling effects, biochar particles sorbed 0.5-1.5 mM biogenic Fe(II) and thereby increased the long-term extent of hematite reduction by 1.4-1.7 fold. Our results suggest that Fe redox cycling may be strongly impacted by pyrogenic carbon in soils with relatively high content of indigenous pyrogenic carbon or substantial application of biochar. PMID- 26836652 TI - Optical properties of polycarbonate/styrene-co-acrylonitrile blends: effects of molecular weight of the matrix. AB - In this paper, the effects of the molecular weight of a polycarbonate (PC) matrix on the phase morphology and optical properties of a PC/styrene-co-acrylonitrile (SAN) blend were investigated. A scanning electron microscope is used to analyze the phase morphology of the blends, and Mie scattering theory is used to analyze the changing laws of the optical properties of PC/SAN blends with the increasing of PC molecular weight. Results show that the average particle diameter is not strongly changed with different PC molecular weight because the values of the viscosity ratios are very close to each other. But it is obvious that the number of large particles gradually reduced while small particles (especially d<2 MUm) significantly increased with the increasing of PC molecular weight. And the increase in small particles will result in an increase in backward scattering so the transmittance of PC/SAN blends decreases with the increase of PC molecular weight. However, the balance of the scattering coefficients and the number concentration of particles eventually lead to the haze of the blends being very close, despite having different PC molecular weights. Meanwhile, the photographs of scattering patterns indicate that the PC/SAN blends whose component weight ratios are fixed at 70:30 have excellent antiglare properties, despite the changes in molecular weight of the PC matrix. PMID- 26836653 TI - Distributed parameter model for characterizing magnetic crosstalk in a fiber optic current sensor. AB - The effects of magnetic crosstalk on a fiber optic current sensor are studied using the distributed parameter model. A new method to enhance the immunity to magnetic crosstalk is proposed. The experimental results show that magnetic crosstalk changes periodically with the azimuth angle and decreases as the distance between the conductors increases. When the sensing coil is placed at the optimal azimuth angle, the ratio error from magnetic crosstalk decreases from 0.32% to -0.02%, demonstrating the effectiveness of the proposed method. PMID- 26836654 TI - Image magnification in lensless holographic projection using double-sampling Fresnel diffraction. AB - Since the diffraction angle is limited by the spatial resolution of the spatial light modulator (SLM), the size of the optical image of the lensless holographic projection with a SLM is very small. Using a divergent spherical beam to illuminate a SLM is an effective method to physically increase the projection angle; nevertheless, the sampling ranges of the existing Fresnel diffraction algorithms with fast Fourier transform keep unchanged. In this paper, a double sampling Fresnel diffraction algorithm to enlarge the sampling range is proposed when using a divergent spherical beam to illuminate a SLM, and the magnification of the optical image is realized in lensless holographic projection. The hologram can be easily optimized by the Gerschberg-Saxton algorithm. Simulation and experimental results with enlarged optical image are presented successfully. PMID- 26836655 TI - Subaperture stitching for measurement of freeform wavefront. AB - A method based on subaperture stitching for measurement of a freeform wavefront is proposed and applied to wavefronts calculated from the slope data acquired using a scanning Shack Hartmann sensor (SHS). The entire wavefront is divided into a number of subapertures with overlapping zones. Each subaperture is measured using the SHS, which is scanned over the entire wavefront. The slope values and thus the phase values of separately measured subapertures cannot be connected directly due to various misalignment errors during the scanning process. The errors lying in the vertical plane, i.e., piston, tilt, and power, are minimized by fitting them in the overlapping zone. The radial and rotational misalignment errors are minimized during registration in the global frame by using active numerical alignment before the stitching process. A mathematical model for a stitching algorithm is developed. Simulation studies are presented based on the mathematical model. The proposed mathematical model is experimentally verified on freeform surfaces of a cubic phase profile. PMID- 26836656 TI - Real-time time-division color electroholography using a single GPU and a USB module for synchronizing reference light. AB - We propose real-time time-division color electroholography using a single graphics processing unit (GPU) and a simple synchronization system of reference light. To facilitate real-time time-division color electroholography, we developed a light emitting diode (LED) controller with a universal serial bus (USB) module and the drive circuit for reference light. A one-chip RGB LED connected to a personal computer via an LED controller was used as the reference light. A single GPU calculates three computer-generated holograms (CGHs) suitable for red, green, and blue colors in each frame of a three-dimensional (3D) movie. After CGH calculation using a single GPU, the CPU can synchronize the CGH display with the color switching of the one-chip RGB LED via the LED controller. Consequently, we succeeded in real-time time-division color electroholography for a 3D object consisting of around 1000 points per color when an NVIDIA GeForce GTX TITAN was used as the GPU. Furthermore, we implemented the proposed method in various GPUs. The experimental results showed that the proposed method was effective for various GPUs. PMID- 26836657 TI - Analysis of a dual-twist Pancharatnam phase device with ultrahigh-efficiency large-angle optical beam steering. AB - It has been previously shown that a Pancharatnam phase device with a dual-twist structure can deflect light up to 60 degrees with nearly perfect efficiency. This was beyond the limits previously assumed for these types of devices, which were considered to be optically similar to Raman-Nath gratings. In this paper we first consider the range of parameters that will allow for high efficiency and show the results for a structure that demonstrates 80 degrees deflection. We then explore the light propagation through these devices to point out interesting intensity variations in the deflected mode of light as it traverses the deflecting layer. Finally, we explain the key to understanding the efficiency of these devices, which is not the typical parameters that are important for traditional diffractive devices, but rather the control of the polarization state of light. We provide a simple design approach for optimizing the twist angle and retardation for high efficiency. PMID- 26836658 TI - Simple method to improve spatial resolution for in vivo two-photon fluorescence imaging. AB - There is a growing effort to image single neurons in vivo, and observe their individual contribution to the brain's functional organization. This effort generally relies on two-photon imaging to explore the structure and activity of cortical columns extending beneath the brain's surface. The need to protect living tissue, however, demands the introduction of coverslips and similar objects that can modify the optics of the imaging beam. This paper develops three dimensional (3D) analytical and numerical models to characterize and correct for the resulting degradation of image quality. We have illustrated the use of these models by describing a simple, practical technique to reduce the effect of spherical aberration for in vivo two-photon fluorescence experiments. PMID- 26836659 TI - Diode-pumped continuous-wave dual-wavelength c-cut Pr3+:LiYF4 laser at 696 and 719 nm. AB - A continuous-wave, InGaN-LD-pumped dual-wavelength laser is demonstrated with simultaneous emission at 696 (3P03F(->)3) and 719 nm (3P03F(->)4) using a c-cut Pr(3+):LiYF4, for the first time to our knowledge. Maximum output power of 102 mW at these two wavelengths is achieved with slope efficiency of about 15.6% with respect to the absorbed pump power. The beam propagation factors in x and y directions are measured to be 1.50 and 1.32, respectively. PMID- 26836660 TI - Distortion correction for microscopic fringe projection system with Scheimpflug telecentric lens. AB - To increase the measurement range of 3D microscopy, Scheimpflug adjustment, in which the imaging plane is tilted with respect to the telecentric lens plane, is often employed. However, the inclined imaging plane will introduce certain distortion to the captured image, which further affects the accuracy of the 3D reconstruction result. In this paper, a distortion model was derived based on the geometric optics theory. With it, the imaging distortion caused by the Scheimpflug condition can be effectively corrected. Experimental results will be presented to demonstrate the feasibility and validity of the proposed method. PMID- 26836661 TI - Thick multilayered (silica/gold) dipole nano-antenna. AB - Nano-antennas are the optical equivalent of antennas that are used to transmit and receive information at radio frequencies. These antennas have been used in different applications in photonics such as optical imaging, particle manipulation, bio-sensing, and improvement of the performance of solar cells. In this article we study composite nano-antennas made of alternating layers of silica and gold. We show that a 50% filling factor leads to a 2.0 times increase in the electric-field enhancement factor when compared with a pure-gold antenna. PMID- 26836662 TI - Multimodal optogenetic neural interfacing device fabricated by scalable optical fiber drawing technique. AB - We present a novel approach to the design and manufacture of optrodes for use in the biomedical research field of optogenetic neural interfacing. Using recently developed optical fiber drawing techniques that involve co-drawing metal/polymer composite fiber, we have assembled and characterized a novel optrode with promising optical and electrical functionality. The fabrication technique is flexible, scalable, and amenable to extension to implantable optrodes with high density arrays of multiple electrodes, waveguides, and drug delivery channels. PMID- 26836663 TI - Aiding phase unwrapping by increasing the number of residues in two-dimensional wrapped-phase distributions. AB - In phase unwrapping residues are points of locally inconsistent phase that occur within a wrapped-phase map, which are usually regarded as being problematic for phase-unwrapping algorithms. Real phase maps typically contain a number of residues that are approximately proportional to the subsequent difficulty in unwrapping the phase distribution. This paper suggests the radical use of the discrete Fourier transform to actually increase the number of residues in 2D phase-wrapped images that contain discontinuities. Many of the additional residues that are artificially generated by this method are located on these discontinuities. For example, in fringe projection systems, such phase discontinuities may come from physical discontinuity between different parts of the object, or by shadows cast by the object. The suggested technique can improve the performance of path independent phase-unwrapping algorithms because these extra residues simplify the process of setting the branch cuts in the wrapped image based on the distance to the nearest residue. The generated residues can also be used to construct more reliable quality maps and masks. The paper includes an initial analysis upon simulated phase maps and goes on to verify the results on a real experimental wrapped-phase distribution. PMID- 26836664 TI - Observation and analysis of the temperature inversion layer by Raman lidar up to the lower stratosphere. AB - The vibration-rotational Raman lidar system built in Xi'an, China (34.233 degrees N, 108.911 degrees E) was used to simultaneously detect atmospheric temperature, water vapor, and aerosols under different weather conditions. Temperature measurement examples showed good agreement with radiosonde data in terms of the lapse rates and heights of the inversion layer under the lower stratosphere. The statistical temperature error due to the signal-to-noise ratio is less than 1 K up to a height of 15 km, and is estimated to be less than 3 K below a height of 22 km. High-quality temperature data were collected from 70 nighttime observations from October 2013 to May 2014, and were used to analyze the temperature inversion characteristics at Xi'an, which is a typical city in the northwest of China. The tropopause height over the Xi'an area was almost 17-18 km, and the inversion layer often formed above the cloud layer. In the winter at night, inversions within the boundary layer can easily form with a high occurrence of ~60% based on 47 nights from 01 November 2013 to 21 January 2014. Continuous observation of atmospheric temperature, water vapor (relative humidity), and aerosols was carried out during one night, and the relevant changes were analyzed in the boundary layer via the joint observation of atmospheric visibility, PM2.5 and PM10 from a ground visibility meter and from a monitoring site, which revealed that the temperature inversion layer has a great influence on the formation of fog and haze during the winter night and early morning. PMID- 26836665 TI - Effect of camera temperature variations on stereo-digital image correlation measurements. AB - In laboratory and especially non-laboratory stereo-digital image correlation (stereo-DIC) applications, the extrinsic and intrinsic parameters of the cameras used in the system may change slightly due to the camera warm-up effect and possible variations in ambient temperature. Because these camera parameters are generally calibrated once prior to measurements and considered to be unaltered during the whole measurement period, the changes in these parameters unavoidably induce displacement/strain errors. In this study, the effect of temperature variations on stereo-DIC measurements is investigated experimentally. To quantify the errors associated with camera or ambient temperature changes, surface displacements and strains of a stationary optical quartz glass plate with near zero thermal expansion were continuously measured using a regular stereo-DIC system. The results confirm that (1) temperature variations in the cameras and ambient environment have a considerable influence on the displacements and strains measured by stereo-DIC due to the slightly altered extrinsic and intrinsic camera parameters; and (2) the corresponding displacement and strain errors correlate with temperature changes. For the specific stereo-DIC configuration used in this work, the temperature-induced strain errors were estimated to be approximately 30-50 MUepsilon/ degrees C. To minimize the adverse effect of camera temperature variations on stereo-DIC measurements, two simple but effective solutions are suggested. PMID- 26836667 TI - Extraction of vibration parameters from optical feedback interferometry signals using wavelets. AB - This paper proposes the use of the wavelet transform as a technique that is suited for fringe detection and analysis of optical feedback interferometry (OFI) signals, thus allowing the retrieval of extremely small physical motion phenomena. A novel algorithm based on wavelet transform is used to process the OFI signal simultaneously in the time and frequency domains, enabling precise detection of signal fringes and, thus, the extraction of amplitude features of the vibrating target with error in the order of 0.1lambda. Furthermore, using a complex Morlet wavelet as an analyzing wavelet enables us to extract important information from the time envelope of the OFI signal. Such an envelope can be useful in detecting fringes even in the presence of speckle reducing the error in a displacement reconstruction. Examples of OFI applications, including nanometric displacement sensing without direction ambiguity as well as the measurement of the frequency and velocity of vibrating targets and the detection in time of no periodic events, are also presented using this wavelet approach. PMID- 26836668 TI - Effect of self-apodization correction on Cross-track Infrared Sounder radiance noise. AB - Self-apodization correction increases noise of the radiance spectra measured by the Cross-track Infrared Sounder (CrIS) in three spectral bands. It also increases noise correlation between spectral channels. The degree of the noise effect depends on the spectral resolution, channel frequency, and detector position in the 3*3 detector grids on the focal planes. The effect is relatively small when CrIS is operated in the normal spectral resolution mode, but can reach to the level of a 76% noise increase and 52% noise correlation in high-frequency channels of the shortwave-band spectra from the corner detectors when CrIS is operated in the full spectral resolution mode. The noise impact of the Hamming apodization applied to CrIS spectra is also discussed. PMID- 26836669 TI - Simplifying numerical ray tracing for two-dimensional non circularly symmetric models of the human eye. AB - Ray tracing is a powerful technique to understand the light behavior through an intricate optical system such as that of a human eye. The prediction of visual acuity can be achieved through characteristics of an optical system such as the geometrical point spread function. In general, its precision depends on the number of discrete rays and the accurate surface representation of each eye's components. Recently, a method that simplifies calculation of the geometrical point spread function has been proposed for circularly symmetric systems [Appl. Opt.53, 4784 (2014)]. An extension of this method to 2D noncircularly symmetric systems is proposed. In this method, a two-dimensional ray tracing procedure for an arbitrary number of surfaces and arbitrary surface shapes has been developed where surfaces, rays, and refractive indices are all represented in functional forms being approximated by Chebyshev polynomials. The Liou and Brennan anatomically accurate eye model has been adapted and used for evaluating the method. Further, real measurements of the anterior corneal surface of normal, astigmatic, and keratoconic eyes were substituted for the first surface in the model. The results have shown that performing ray tracing, utilizing the two dimensional Chebyshev function approximation, is possible for noncircularly symmetric models, and that such calculation can be performed with a newly created Chebfun toolbox. PMID- 26836670 TI - Unicursal random maze tool path for computer-controlled optical surfacing. AB - A novel unicursal random maze tool path is proposed in this paper, which can not only implement uniform coverage of the polishing surfaces, but also possesses randomness and multidirectionality. The simulation experiments along with the practical polishing experiments are conducted to make the comparison of three kinds of paths, including maze path, raster path, and Hilbert path. The experimental results validate that the maze path can warrant uniform polishing and avoid the appearance of the periodical structures in the polished surface. It is also more effective than the Hilbert path in restraining the mid-spatial frequency error in computer-controlled optical surfacing process. PMID- 26836671 TI - Fabrication of electroless nickel plated aluminum freeform mirror for an infrared off-axis telescope. AB - Freeform mirrors can be readily fabricated by a single point diamond turning (SPDT) machine. However, this machining process often leaves mid-frequency errors (MFEs) that generate undesirable diffraction effects and stray light. In this work, we propose a novel thin electroless nickel plating procedure to remove MFE on freeform surfaces. The proposed procedure has a distinct advantage over a typical thick plating method in that the machining process can be endlessly repeated until the designed mirror surface is obtained. This is of great importance because the sophisticated surface of a freeform mirror cannot be optimized by a typical SPDT machining process, which can be repeated only several times before the limited thickness of the nickel plating is consumed. We will also describe the baking process of a plated mirror to improve the hardness of the mirror surface, which is crucial for minimizing the degradation of that mirror surface that occurs during the polishing process. During the whole proposed process, the changes in surface figures and textures are monitored and cross checked by two different types of measurements, as well as by an interference pattern test. The experimental results indicate that the proposed thin electroless nickel plating procedure is very simple but powerful for removing MFEs on freeform mirror surfaces. PMID- 26836672 TI - Monte Carlo simulation for speckle reduction by a moving diffuser on the natural test image. AB - We present a precise Monte Carlo simulation of speckle reduction on the natural test image, which will serve as a digital image embedded with speckle under control. In simulating the conditioned time averaging for the square modulus of the random phasor sum in speckle reduction by a moving diffuser, after initial upconversion of the test image amplitudes, downconversion of their product with an independent set of time-varying, random phasors is repeated to sum up the square moduli. Validity of the simulation is rigorously confirmed on the test image array consisting of random real amplitude. As a more practical digital test image for speckle evaluation, the well-known Lena test image is promising as the standard for this application from the point of view of sufficiently small excess noise, primarily due to low pixel-neighbor correlations. PMID- 26836673 TI - Optical description and design method with annularly stitched aspheric surface. AB - The relentless pressure for designs with new optical functions, small volume, and light weight has greatly increased the importance of aspheric surfaces. In this paper, we propose an annularly stitched aspheric surface (ASAS) description method to increase the freedom and flexibility of imaging system design. The rotationally symmetric ASAS consists of a circular central zone and one or more annular zones. Two neighboring zones are constrained to have the same derivatives on their joint curve, and this means the ASAS is C1 continuous. This finding is proved and verified by the mathematical deduction of the surface formulas. Two optimization strategies and two design methods with the C1 continuous constraints are also discussed. This surface can greatly facilitate the design and even achieve some previously impossible designs without increasing the fabrication difficulty. Two different systems with the proposed ASAS are optimized and the results are presented. The design results verified the practicability of the ASAS. PMID- 26836674 TI - Modeling of high-precision wavefront sensing with new generation of CMT avalanche photodiode infrared detectors. AB - Near-infrared wavefront sensing allows for the enhancement of sky coverage with adaptive optics. The recently developed HgCdTe avalanche photodiode arrays are promising due to their very low detector noise, but still present an imperfect cosmetic that may directly impact real-time wavefront measurements for adaptive optics and thus degrade performance in astronomical applications. We propose here a model of a Shack-Hartmann wavefront measurement in the presence of residual fixed pattern noise and defective pixels. To adjust our models, a fine characterization of such an HgCdTe array, the RAPID sensor, is proposed. The impact of the cosmetic defects on the Shack-Hartmann measurement is assessed through numerical simulations. This study provides both a new insight on the applicability of cadmium mercury telluride (CMT) avalanche photodiodes detectors for astronomical applications and criteria to specify the cosmetic qualities of future arrays. PMID- 26836675 TI - Optical characterization of gaps in directly bonded Si compound optics using infrared spectroscopy. AB - Silicon direct bonding offers flexibility in the design and development of Si optics by allowing manufacturers to combine subcomponents with a potentially lossless and mechanically stable interface. The bonding process presents challenges in meeting the requirements for optical performance because air gaps at the Si interface cause large Fresnel reflections. Even small (35 nm) gaps reduce transmission through a direct bonded Si compound optic by 4% at lambda=1.25 MUm at normal incidence. We describe a bond inspection method that makes use of precision slit spectroscopy to detect and measure gaps as small as 14 nm. Our method compares low-finesse Fabry-Perot models to high-precision measurements of transmission as a function of wavelength. We demonstrate the validity of the approach by measuring bond gaps of known depths produced by microlithography. PMID- 26836676 TI - High-speed infrared imaging by an uncooled optomechanical focal plane array. AB - In this paper, we theoretically and experimentally demonstrate that the imaging speed of the optomechanical focal plane array infrared imaging system can be significantly improved by changing the pressure in the vacuum chamber. The decrease in the thermal time constant is attributed to the additional thermal conductance caused by air. The response time will be greatly shortened to about 1/3 time in low vacuum (around ~10(2) Pa) compared with that in high vacuum. At a chamber pressure of 50 Pa, the "trailing" in the IR image of a moving hot iron is eliminated with negligible deterioration in the image quality. Moreover, infrared images on rapid occurrence events, such as ignition of an alcohol blast burner, lighting and fusion of a tungsten filament, are captured at a frame rate up to 200 Hz. The above results show that the proposed pressure-dependent performance provides a way to improve the system imaging speed and helps to slow down a dynamic event, which is of great value to the uncooled IR imaging systems in practical applications. PMID- 26836677 TI - Homodyne laser vibrometer capable of detecting nanometer displacements accurately by using optical shutters. AB - This paper describes a homodyne laser vibrometer with optical shutters. The parameters that define the nonlinearity of the quadrature signals in a vibrometer can be pre-extracted before the measurement, and can then be used to compensate for nonlinear errors, such as unequal AC amplitudes and DC offsets. The experimental results indicated that the homodyne laser vibrometer developed has the ability to accurately detect the vibration state of the object to be measured, even when the amplitude is <=lambda/4. The displacement residual error can be reduced to a value under 0.9 nm. PMID- 26836678 TI - Use of diffraction grating for measuring the focal length and distortion of optical systems. AB - The paper presents an experimentally simple, accurate, and inexpensive method for measuring the focal length and distortion of optical systems using a diffraction grating, where both of the properties are determined from the transversal distances of diffraction maximums in one measurement. The proposed approach does not require any special components or any expensive equipment. A detailed theoretical analysis is performed, and the estimation of uncertainties is studied as well. Afterward, the method is demonstrated with a computer simulation and experimental measurement, and compared with commercially available measurement devices. It is shown that the method provides sufficiently accurate results for many practical applications; therefore, it is appropriate for laboratory testing and for industrial applications. PMID- 26836679 TI - Optimization of adiabatic microring resonators with few-mode and high-Q resonances. AB - We present the theoretical analysis and experimental demonstration of adiabatic microring resonators. The resonators are halfway between microdisk and microring preserving the good properties of both the microdisk (high Q-factor) and the microring (internal mode rejection). Device modeling based on the coupled-mode theory suggests that both the internal and external decay rates should be low in order to obtain high-Q and high extinction ratio resonances. The internal decay is modal-order-dependent and significantly affected by the adiabatic tapering rate of the ring waveguide. The external delay is determined by the modal effective index difference between the bus and ring waveguides at the coupling point under a fixed gap. Upon optimization of the resonator system, two resonance modes in the measured device are measured with one possessing a high Q-factor. PMID- 26836680 TI - Enhanced scanning agility using a double pair of Risley prisms. AB - Scanners with one pair of Risley prisms are robust and precise and they can be operated continuously. In this paper, we present a new scanner based on the use of two pairs of Risley prisms. The concept was driven by the need to add flexibility to Risley prism scanners used for lidar 3D mapping applications, while maintaining compactness and robustness. The first pair covers a FOV narrower than the second pair. The second pair is used to position the first Risley pair scan pattern anywhere within its own, larger, FOV. Doing so, it becomes possible, without additional scanner components, to increase the sampling point density at a specific location, to increase the sampling uniformity of the scanned area, and, while in motion, to maintain the sampling of a specific area of interest. PMID- 26836681 TI - High Miller-index germanium crystals for high-energy x-ray imaging applications. AB - Near-normal-incidence bent crystals are widely used for x-ray imaging applications. Advantages include high collection solid angle and potentially high efficiency for narrow-band sources, while disadvantages include relatively large (several A) interatomic spacings and a limited number of suitable matches between a crystal 2d value and an integral multiple of useful emission line wavelengths. The disadvantages become more significant at x-ray energies >10 keV. The former disadvantage can be mitigated by using high-order reflections from crystal planes having low Miller indices, but both disadvantages can be mitigated by using low order reflections from crystal planes having high Miller indices. We report here on integrated reflectivity measurements we performed of Ge (15,7,7) (2d=0.6296 A), a candidate for imaging Ru He-alpha (theta(B)=87 degrees ). We find good agreement with calculations, and the data show a multitude of closely spaced reflections with slightly different Bragg angles including a fifth-order reflection of Ge (3,1,1) that has comparable reflectivity. This demonstrates that arbitrary choices of Miller indices in Ge crystals can be used to fine-tune Bragg angles for near-normal-incidence x-ray imaging at tens of kiloelectron volt x-ray energies with minimal lower-energy contamination from lower-order reflections, and that existing calculational tools can be used to reliably estimate integrated reflectivity. PMID- 26836682 TI - Visibly transparent organic photovoltaic with improved transparency and absorption based on tandem photonic crystal for greenhouse application. AB - We demonstrate a visible transparent organic photovoltaic (OPV) with improved transmission and absorption based on tandem photonic crystals (TPCs) for greenhouse applications. The proposed device has an average transmittance of 40.3% in the visible range of 400-700 nm and a high quality transparency spectrum for plant growth with a crop growth factor of 41.9%, considering the weight of the AM 1.5G solar spectrum. Compared with the corresponding transparent OPV without photonic crystals, an enhancement of 20.7% in the average transmittance and of 24.5% in the crop growth factor are achieved. Detailed investigations reveal that the improved transmittance is attributed to the excitation of the optical Tamm state and the light interference effect in TPC. Concomitantly, the total absorption efficiency in the active layer of the designed TPC based transparent OPV reaches 51.5%, being 1.78% higher than that of the transparent OPV without PC and 76% of that of the opaque counterpart. The improved absorption originates from the Bragg forbidden reflectance of TPC. Overall, our proposal achieves the optimized utilization of sunlight by light manipulation of TPC. PMID- 26836683 TI - Investigation of collimating and focusing lenses' impact on laser diode stack beam parameter product. AB - The paper presents a new expression for determining the beam parameter product of a multi-emitter laser diode module made by stacking several single emitter chips. The proposed formula takes into account the effect of collimating and focusing lenses and has been validated experimentally, obtaining excellent agreement between theoretical expectations and measurements. A practical application to optimize the lenses' configuration for the design of a fiber-coupled multi emitter module is also reported. PMID- 26836684 TI - Improvement of high-order least-squares integration method for stereo deflectometry. AB - Stereo deflectometry is defined as measurement of the local slope of specular surfaces by using two CCD cameras as detectors and one LCD screen as a light source. For obtaining 3D topography, integrating the calculated slope data is needed. Currently, a high-order finite-difference-based least-squares integration (HFLI) method is used to improve the integration accuracy. However, this method cannot be easily implemented in circular domain or when gradient data are incomplete. This paper proposes a modified easy-implementation integration method based on HFLI (EI-HFLI), which can work in arbitrary domains, and can directly and conveniently handle incomplete gradient data. To carry out the proposed algorithm in a practical stereo deflectometry measurement, gradients are calculated in both CCD frames, and then are mixed together as original data to be meshed into rectangular grids format. Simulation and experiments show this modified method is feasible and can work efficiently. PMID- 26836685 TI - Large Kerr index with amplification in an open four-level atomic system with twofold lower levels. AB - This paper presents a new freedom, which is the result of atomic injection and exit rates from a cavity associated with an open system, thus leading to a remarkable giant Kerr nonlinearity with applications in all-optical switching. The influence of atomic injection and exit rate from the cavity on nonlinear susceptibility of an open four-level Lambda-type atomic system with twofold lower levels is investigated. It is found that large Kerr nonlinearity accompanied with probe gain can be obtained by adjusting the atomic injection rates and exit rate from the cavity, which is completely different from those presented in previous closed atomic systems. Phase control of Kerr nonlinearity in such an open atomic system is then studied. PMID- 26836686 TI - Study of atomic and molecular emission spectra of Sr by laser induced breakdown spectroscopy (LIBS). AB - Laser Induced Breakdown Spectroscopy (LIBS) is an ideal analytical technique for in situ analysis of elemental composition. We have performed a comparative study of the quantitative and qualitative analysis of atomic and molecular emission from LIBS spectra. In our experiments, a mixture of SrCl2 and Al2O3 in powder form was used as a sample. The atomic emission from Sr and molecular emission from SrCl and SrO observed in LIBS spectra were analyzed. The optimum laser energies, gate delays, and gate widths for selected atomic lines and molecular bands were determined from spectra recorded at various experimental parameters. These optimum experimental conditions were used to collect calibration data, and the calibration curves were used to predict the Sr concentration. Limits of detection (LODs) for selected atomic and molecular emission spectra were determined. PMID- 26836688 TI - Compact high extinction ratio asymmetric polarization beam splitter of periodic rods waveguide. AB - A compact high extinction ratio polarization beam splitter based on an asymmetric directional coupler was proposed and theoretically investigated. The asymmetric directional coupler consists of a silicon wire waveguide and a 1D periodic silicon rods waveguide, which results in an ultracompact polarization splitting length. By using the plane wave expansion method, a minimum coupling length of 3.43 MUm was obtained, and the length was then confirmed by finite-difference time-domain simulation. Moreover, for 1550 nm wavelength, high extinction ratios of about 28 and 18 dB were also observed for TE and TM polarizations, respectively. The ultrahigh extinction ratio for TE polarization is mainly arising from the appearance of TM bandgap in the periodic rods waveguide. In addition, for both polarizations, the extinction ratios are all above 10 dB covering a 180 nm bandwidth, and it was also demonstrated that the device has a high transmission for TM polarization. PMID- 26836687 TI - Doubly Q-switched Ho:LuAG laser with acoustic-optic modulator and Cr2+:ZnS saturable absorber. AB - A doubly Q-switched (DQS) Ho:LuAG laser resonantly pumped by a 1.91-MUm laser was first presented with an acoustic-optic modulator (AOM) and a Cr2+:ZnS saturable absorber. A comparison among the active Q-switched (AQS), passively Q-switched (PQS), and DQS laser performances was carried out. The maximum continuous wave (CW) output power of 6 W with the central wavelength of 2100.65 nm was obtained at an incident pump power of 35.2 W. Compared with CW laser, the AQS, PQS, and DQS lasers shared the same central wavelength of 2098.34 nm under the same incident pump power. The central wavelength of the AQS and DQS lasers remained constant with the change of AOM repetition frequency (RF). When the incident pump power was 35.2 W and the AOM RF was 15 kHz, the DQS Ho:LuAG laser at a maximum RF of 2.13 kHz achieved the maximum average output power of 4.95 W. At the AOM RF of 10 kHz, the DQS Ho:LuAG laser achieved the shortest pulse width of 40.4 ns with the highest peak power of 61.5 kW. At an incident pump power of 35.2 W, the PQS Ho:LuAG laser obtained the shortest pulse width of 46.1 ns, corresponding to the RF of 2.25 kHz. Experiment results showed that the pulse width could be compressed effectively with a significant increase of peak power for a 2-MUm DQS laser. PMID- 26836689 TI - Modeling seawater salinity and temperature sensing based on directional coupler assembled by polyimide-coated micro/nanofibers. AB - The salinity and temperature of seawater are important parameters in oceanography. Based on the directional coupler assembled by polyimide-coated micro/nanofibers, optical sensors with high sensitivity for simultaneous salinity and temperature sensing in seawater are proposed. Dependences of sensitivities on wavelength, salinity, and temperature are investigated theoretically, with which performances of such sensor under general sea conditions can be evaluated. Results show that salinity and temperature sensitivities can reach levels of nm/0/00 and nm/ degrees C, which are much higher than those of fiber Bragg gratings, knot resonators, and photonic crystal fibers. Other considerations for system design such as the length of the coupling area, the diameter difference between two fibers, and the thickness of polyimide coatings are also discussed. Sensors proposed here suggest a simple approach to realize high-sensitivity micro/nanofiber optical sensing of salinity and temperature in seawater simultaneously and may find applications in developing miniature sensors used in seawater. PMID- 26836691 TI - Simple method for measuring the linewidth enhancement factor of semiconductor lasers. AB - A simple method for measuring the linewidth enhancement factor (LEF) of semiconductor lasers (SLs) is proposed and demonstrated in this paper. This method is based on the self-mixing effect when a small portion of optical signal intensity emitted by the SL reflected by the moving target re-enters the SL cavity, leading to a modulation in the SL's output power intensity, in which the modulated envelope shape depends on the optical feedback strength as well as the LEF. By investigating the relationship between the light phase and power from the well-known Lang and Kobayashi equations, it was found that the LEF can be simply measured from the power value overlapped by two SLs' output power under two different optical feedback strengths. Our proposed method is verified by both simulations and experiments. PMID- 26836690 TI - Thulium/holmium-doped fiber laser passively mode locked by black phosphorus nanoplatelets-based saturable absorber. AB - By coupling black phosphorus (BP) nanoplatelets (NPs) with a fiber-taper evanescent light field, a saturable absorber (SA) based on the BP NPs has been successfully fabricated and used in a thulium/holmium-doped fiber laser as the mode locker. The SA had a modulation depth of ~9.8% measured at 1.93 MUm. A stable mode-locking operation at 1898 nm was achieved with a pulse width of 1.58 ps and a fundamental mode-lock repetition rate of 19.2 MHz. By increasing the pump intensity, phenomena of multi-pulsing operations, including harmonic mode locked states and soliton bunches, were obtained in the experiment, showing that the BP NPs possess an ultrafast optical response time. This work suggests that the BP NPs-based SA is potentially useful for ultrashort, pulsed laser operations in the eye-safe region of 2 MUm. PMID- 26836692 TI - Aspect ratio engineering of microlens arrays in thin-film flip-chip light emitting diodes. AB - Light extraction efficiency of thin-film flip-chip InGaN-based light-emitting diodes (LEDs) with a TiO2 microlens arrays was calculated by employing the finite difference time-domain method. The microlens arrays, formed by embedding hexagonal close-packed TiO2 sphere arrays in a polystyrene (PS) layer, were placed on top of the InGaN LED to serve as an intermediate medium for light extraction. By tuning the thickness of the PS layer, in-coupling and out-coupling efficiencies were optimized to achieve maximum light extraction efficiency. A thicker PS layer resulted in higher in-coupling efficiency, while a thinner PS layer led to higher out-coupling efficiency. Thus, the maximum light extraction efficiency becomes a trade-off between in-coupling and out-coupling efficiency. In addition, the cavity formed by the PS layer also affects light extraction from the LED. Our study reveals that a maximum light extraction efficiency of 86% was achievable by tuning PS thickness to 75 nm with maximized in-coupling and out coupling efficiency accompanied by the optimized resonant cavity condition. PMID- 26836693 TI - Loss of DJ-1 impairs antioxidant response by altered glutamine and serine metabolism. AB - The oncogene DJ-1 has been originally identified as a suppressor of PTEN. Further on, loss-of-function mutations have been described as a causative factor in Parkinson's disease (PD). DJ-1 has an important function in cellular antioxidant responses, but its role in central metabolism of neurons is still elusive. We applied stable isotope assisted metabolic profiling to investigate the effect of a functional loss of DJ-1 and show that DJ-1 deficient neuronal cells exhibit decreased glutamine influx and reduced serine biosynthesis. By providing precursors for GSH synthesis, these two metabolic pathways are important contributors to cellular antioxidant response. Down-regulation of these pathways, as a result of loss of DJ-1 leads to an impaired antioxidant response. Furthermore, DJ-1 deficient mouse microglia showed a weak but constitutive pro inflammatory activation. The combined effects of altered central metabolism and constitutive activation of glia cells raise the susceptibility of dopaminergic neurons towards degeneration in patients harboring mutated DJ-1. Our work reveals metabolic alterations leading to increased cellular instability and identifies potential new intervention points that can further be studied in the light of novel translational medicine approaches. PMID- 26836694 TI - Biomimetic Design Results in a Potent Allosteric Inhibitor of Dihydrodipicolinate Synthase from Campylobacter jejuni. AB - Dihydrodipicolinate synthase (DHDPS), an enzyme required for bacterial peptidoglycan biosynthesis, catalyzes the condensation of pyruvate and beta aspartate semialdehyde (ASA) to form a cyclic product which dehydrates to form dihydrodipicolinate. DHDPS has, for several years, been considered a putative target for novel antibiotics. We have designed the first potent inhibitor of this enzyme by mimicking its natural allosteric regulation by lysine, and obtained a crystal structure of the protein-inhibitor complex at 2.2 A resolution. This novel inhibitor, which we named "bislysine", resembles two lysine molecules linked by an ethylene bridge between the alpha-carbon atoms. Bislysine is a mixed partial inhibitor with respect to the first substrate, pyruvate, and a noncompetitive partial inhibitor with respect to ASA, and binds to all forms of the enzyme with a Ki near 200 nM, more than 300 times more tightly than lysine. Hill plots show that the inhibition is cooperative, indicating that the allosteric sites are not independent despite being located on opposite sides of the protein tetramer, separated by approximately 50 A. A mutant enzyme resistant to lysine inhibition, Y110F, is strongly inhibited by this novel inhibitor, suggesting this may be a promising strategy for antibiotic development. PMID- 26836695 TI - Progression of Coronal Cobb Angle After Short-Segment Lumbar Interbody Fusion in Patients with Degenerative Lumbar Stenosis. AB - OBJECTIVE: The progression of scoliosis after fusion surgery is a poor prognostic factor of long-term outcomes in patients with degenerative lumbar stenosis (DLS). In this study we aimed to investigate changes in coronal alignment and identify risk factors related to progression of scoliosis after fusion. METHODS: There were 540 patients with symptomatic DLS treated by short-segment lumbar fusion surgery. Among them, 50 patients had coronal Cobb angles >10 degrees at the final follow-up. Sixteen patients had increases >5 degrees (progression group), and 34 patients had increases <5 degrees (nonprogression group). Radiologic parameters that may affect the progression of scoliosis were compared. RESULTS: The mean progression of the Cobb angle was 7.92 degrees in the progression group and 1.25 degrees in the nonprogression group. The progression group had significantly longer follow-up periods and a lower preoperative Cobb angle. The apical vertebra (AV) of the major curve was more frequently thoracic in the progression group. Progression of the Cobb angle was correlated with the follow up period, preoperative Cobb angle, and location of the AV. Multivariate regression analysis showed that progression of the Cobb angle was significantly associated with a lower preoperative Cobb angle, and both facet degeneration of the upper instrumented vertebra at the fusion site and vertebral spur formation on the concave side also appeared to be associated with progression of the Cobb angle. CONCLUSIONS: The global magnitude of progression of the Cobb angle after short-segment lumbar fusion surgery in patients with DLS is similar to the natural curve progression of adult degenerative scoliosis. PMID- 26836696 TI - Preliminary Analysis of Adjacent Segment Degeneration in Patients Treated with Posterior Cervical Cages: 2-Year Follow-Up. AB - OBJECTIVE: Select patients with unremitting symptoms of cervical radiculopathy may be treated with indirect foraminal decompression and fusion via placement of a cervical cage placed bilaterally through a tissue sparing, posterior approach. Segmental fusion is known to affect adjacent segments. The aim of this study was to assess the affect of posterior fusion using bilateral cervical cages on adjacent segment degeneration (ASDegeneration) at 2 years postoperatively. METHODS: Fifty-three patients enrolled in a prospective multicenter study who completed the imaging protocol were available for follow-up at 2 years. Lateral cervical radiographs were acquired preoperatively and at 1- and 2-years postoperatively. Imaging was evaluated for adjacent level degeneration using the following criteria: disk height ratio (DHR) defined as the ratio of the disk height and the lower vertebrae height measured at level above and below; proximal junctional kyphosis (PJK); Kellgren and Lawrence osteoarthritis severity grade (KLOSG); and heterotopic ossification (HO). The results were compared with a repeated analysis of variance test and Bonferroni correction; P < 0.05 was considered significant. RESULTS: At 2 years postoperatively, there were no revision surgeries at the operated level or new surgeries at the adjacent levels. Of the 102 segments evaluated, ASDegeneration was identified at 21 levels cranial to and 21 levels caudal to the index level. At 2 years, new mild ASDegeneration signs developed at 3 levels: 1 in the level above and 2 in the level below the operated segment. In patients with pre-existing disk degeneration, mild progression of ASDegeneration signs developed in 6 upper and 2 lower segments. There were no significant changes in DHR and PJK in all patients; however, when patients with signs of ASDegeneration only were evaluated, a significant decrease of the DHR was found. The mean DHRs before surgery and 1 and 2 years after surgery in all patients were 44.0 +/- 8.1, 44.0 +/- 8.2, and 43.1 +/- 8.4 (P = 0.1006) and in ASD patients were 43.8 +/- 7.3, 41.9 +/- 6.3, and 39.6 +/- 8.3 (P = 0.0062), respectively. Overall, at 2 years postoperatively, ASDegeneration was identified in 9 patients (17.6% when compared with all evaluated patients before surgery). CONCLUSIONS: In the current study, 5.9% of subjects treated with posterior cervical cages placed bilaterally between the facet joints developed adjacent segment degeneration at 2 years. Mild progression of existing degeneration was observed in 11.8% of subjects. Further evaluation to establish long-term incidence is needed. PMID- 26836697 TI - Three-Dimensional Endoscopic Endonasal Approach and Outcomes in Sellar Lesions: A Single-Center Experience of 104 Cases. AB - BACKGROUND: Pituitary tumors account for approximately 15% of primary intracranial neoplasms and often are diagnosed incidentally. Common sellar lesions are pituitary adenomas, craniopharyngiomas, and Rathke cleft cysts. Currently endoscopic transsphenoidal approaches are largely used, and many centers also use 3-dimensional (3D) technology, although additional results of long-term follow-up are still being accumulated. METHODS: We present a retrospective analysis of 104 patients with sellar lesions (57 male and 47 female, mean age 52 years) who underwent 3D endoscopic transsphenoidal surgery in our center from December 2011 to March 2015 and were followed up for a mean time of 18 months. RESULTS: A total of 16 patients were diagnosed with growth hormone secreting adenomas, 9 with adrenocorticotropic hormone-secreting, 5 with prolactin-secreting, and 2 with thyroid-stimulating hormone-secreting tumors and 58 with nonsecreting pituitary adenomas. Five patients had Rathke cleft cysts, 5 craniopharyngiomas, 2 fibrous solitary tumors, 1 a metastasis, and 1 a chordoma. At baseline, 47 patients (45.2%) had hormonal changes and 52 (50%) had visual field changes. Complete resection was achieved in 73 patients (70.1%). Follow-up evaluation detected hormonal remission in 7 patients with Cushing disease (77.7%) and in 11 patients with acromegaly (68.7%). Complications were cerebrospinal fluid leak in 5 cases (4.8%) and transient diabetes insipidus in 6 cases (5.7%). A total of 55 patients (52.9%) were discharged less than 72 hours after surgery. CONCLUSIONS: The use of an endoscopic endonasal approach with 3D technology provides several advantages relating to patient length of stay, rate of complications, postoperative recovery, and novice surgeons' training. Advantages of 3D endoscopy and long-term follow-up still need further elucidation. PMID- 26836698 TI - Intraventricular Hemangiopericytoma: A Case Report and Literature Review. AB - BACKGROUND: Hemangiopericytomas are rare intracranial neoplasms that generally occur in the fifth decade of life and are commonly dural-based, supratentorial tumors. They are classified as World Health Organization grade II or III because of their aggressive nature with high rates of local recurrence and distant metastasis. This case is of an intraventricular hemangiopericytoma in a 23-year old man. Intraventricular locations are rare, with only 10 cases reported in the literature. Our patient is the youngest to be diagnosed with an intraventricular hemangiopericytoma outside a pediatric case discovered at autopsy. CLINICAL PRESENTATION: A 23-year-old man with a left intraventricular hemangiopericytoma presenting with headache, word-finding difficulties, blurred vision, nausea, vomiting, photophobia, and right-sided weakness and numbness. Using a left superior parietal lobule approach, a piecemeal resection was completed, achieving radiographic gross total resection. Pathology was consistent with a hemangiopericytoma. He was treated adjunctively with 60 Gy of local radiation. At 6-month follow-up, the patient had resolution of his aphasia and improvement in his headaches, with no signs of recurrence or metastasis on imaging. CONCLUSIONS: Standard treatment for central nervous system hemangiopericytoma includes aggressive surgical resection. The role of adjuvant radiation is less well defined but is commonly pursued postoperatively. Regardless of extent of resection or adjuvant treatment, close follow-up to evaluate for evidence of local recurrence and distant metastasis is essential. PMID- 26836699 TI - Unilateral Endoscopic Endonasal Surgery for Resection of an Olfactory Schwannoma of the Anterior Cranial Base in a Patient with Hereditary Hemorrhagic Telangiectasia. AB - BACKGROUND: Olfactory schwannomas of the anterior cranial base (ACB) are rare tumors, and their association with hereditary hemorrhagic telangiectasia (HHT) has not previously been described. The majority of ACB schwannomas arise from the sinonasal tracts and may demonstrate intracranial extension. We report a case of an olfactory schwannoma-dense adherence to the basal frontal lobe. Complete tumor resection was performed through a unilateral extended endonasal endoscopic approach with preservation of the contralateral olfactory bulb. Anterior cranial base repair was achieved with the use of a mucoperichondrial vascularized pedicled nasoseptal flap. CLINICAL PRESENTATION: A 25-year-old woman with a history of migraines presented with unilateral epistaxis and progressive worsening of her headache symptoms. The patient had a history of HHT. Nasal endoscopy showed mild telangiectasias, but no clear evidence of a mass. A computerized tomographic scan showed a large left-sided expansile lesion in the left ethmoid region with expansion and remodeling of the anterior cranial base and medial left orbit. Magnetic resonance imaging with contrast showed the mass to be avidly enhancing. Angiography was performed and demonstrated a mild vascular blush. CONCLUSIONS: We report a rare case of HTT and olfactory schwannoma completely resected with a unilateral extended endoscopic endonasal approach. Reconstruction was performed with the use of nasoseptal flap. This is the first reported single-stage fully endoscopic endonasal unilateral approach for resection of an olfactory schwannoma with preservation of the contralateral olfactory cleft. The patient's sense of smell and taste was maintained after surgery. PMID- 26836700 TI - Primary High-Grade Osteosarcoma of the Clivus: A Case Report and Literature Review. AB - BACKGROUND: Osteosarcoma is the second most common primary tumor of the skeletal system and the most common primary bone tumor. Usually occurring at the metaphysis of long bones, osteosarcomas are highly aggressive lesions that comprise osteoid-producing spindle cells. Craniofacial osteosarcomas comprise <8% and are believed to be less aggressive and lower grade. Primary osteosarcomas of the skull and skull base comprise <2% of all skull tumors. Osteosarcomas originating from the clivus are rare. We present a case of a primar, high-grade clival osteosarcoma. CASE DESCRIPTION: A 29-year-old man presented to our institution with a progressively worsening right frontal headache for 3 weeks. There were no sensory or cranial nerve deficits. Computed tomography revealed a destructive mass involving the clivus with extension into the left sphenoid sinus. Magnetic resonance imaging revealed a homogenously enhancing lesion measuring 2.7 * 2.5 * 3.2 cm. The patient underwent endonasal transphenoidal surgery for gross total resection. The histopathologic analysis revealed proliferation of malignant-appearing spindled and epithelioid cells with associated osteoclast-like giant cells and a small area of osteoid production. The analysis was consistent with high-grade osteosarcoma. The patient did well and was discharged on postoperative day 2. He was referred for adjuvant radiation therapy and chemotherapy. Two-year follow-up showed postoperative changes and clival expansion caused by packing material. CONCLUSIONS: Osteosarcoma is a highly malignant neoplasm. These lesions are usually found in the extremities; however, they may rarely present in the craniofacial region. Clival osteosarcomas are relatively infrequent. We present a case of a primary clival osteosarcoma with high-grade pathology. PMID- 26836701 TI - Isolation of Shiga Toxin-Producing Escherichia coli from Ground Beef Using Multiple Combinations of Enrichment Broths and Selective Agars. AB - Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens, and beef cattle are recognized as the principal reservoir. The aims of this study were (1) to identify the most sensitive combination of selective enrichment broths and agars for STEC isolation in artificially inoculated ground beef samples, and (2) to evaluate the most efficient combination(s) of methods for naturally contaminated ground beef samples. A total of 192 ground beef samples were artificially inoculated with STEC and non-stx bacterial strains. A combination of four enrichment broths and three agars were evaluated for sensitivity, specificity, and positive predictive value for STEC isolation from experimentally inoculated samples. Enrichments with either modified tryptic soy broth (mTSB) containing 8 mg/L novobiocin (mTSB-8) or modified Escherichia coli (mEC) broth followed by isolation in MacConkey agar were the most sensitive combinations for STEC isolation of artificially inoculated samples. Independently, both enrichments media followed by isolation in MacConkey were used to evaluate ground beef samples from 43 retail stores, yielding 65.1% and 58.1% stx-positive samples by RT-PCR, respectively. No difference was observed in the isolate proportions between these two methods (8/25 [32%] and 8/28 [28.6%]). Identical serotypes and stx genotypes were observed in STEC strains isolated from the same samples by either method. In this study, no single enrichment protocol was sufficient to detect all STEC in artificially inoculated samples and had considerable variation in detection ability with naturally contaminated samples. Moreover, none of the single or combinations of multiple isolation agars used were capable of identifying all STEC serogroups in either artificially inoculated or naturally occurring STEC-contaminated ground beef. Therefore, it may be prudent to conclude that there is no single method or combination of isolation methods capable of identifying all STEC serogroups. PMID- 26836703 TI - Protective effects of resin sealant and flowable composite coatings against erosive and abrasive wear of dental hard tissues. AB - OBJECTIVES: To test the effectiveness of sealant and flowable composite coating on eroded enamel, dentin and cementum under erosive/abrasive challenges in vitro. METHODS: A total of 108 tissue sections (36 each for enamel, dentin and cementum) from third molars were assigned to three groups: Seal & Protect sealant (S&P), Tetric EvoFlow composite (TEF) and control. Erosive/abrasive lesions were created on each specimen by citric acid and brushing with toothpaste. S&P and TEF were applied to the lesions and subjected to erosive/abrasive cycling included 24 cycles of immersion in citric acid (pH 3.6) for 60min, followed by remineralization for 120min and brushing with toothpastes for 600 strokes at 150g. Erosive wear of materials or dental tissues were measured with 3D scanning microscopy and data were analyzed using ANOVA. RESULTS: Treatments with S&P and TEF created a protective material coating of 42.7+/-17.8MUm and 150.8+/-9.9MUm in thickness, respectively. After 24 cycles of erosive/abrasive challenges, tissue losses were -346.9+/-37.3MUm for enamel, -166.5+/-26.3MUm for dentin and -164.7+/ 18.2MUm for cementum in untreated controls, as compared to material losses of 24.4+/-3.3MUm for S&P, and -10.8+/-4.4MUm for TEF, respectively. Both S&P and TEF were effective in protecting enamel, dentin and cementum against erosive tooth wear (p<0.01). S&P exhibited faster wear than TEF (p<0.01) and showed spotted peeling in a third of the specimens. TEF remained intact on all three types of dental tissues at the end of the 24 cycles of erosive/abrasive challenges. CONCLUSIONS: A thin coating of flowable composite resin 150MUm in thickness may provide long-term protection against erosive/abrasive tooth wear. Resin sealant may provide adequate protection for dental hard tissues in short-term and may require repeated applications if long-term protection is desired. PMID- 26836702 TI - Cyano Group Removal from Cyano-Promoted Aza-Diels-Alder Adducts: Synthesis and Structure-Activity Relationship of Phenanthroindolizidines and Phenanthroquinolizidines. AB - Phenanthroindolizidines and phenanthroquinolizidines were concisely synthesized by the reductive decyanization of cyano-promoted intramolecular aza-Diels-Alder cycloadducts followed by aryl-aryl coupling. Cyano groups were removed from alpha aminoacrylonitriles via treatment with sodium borohydride in 2-propanol in almost quantitative yields; a possible mechanism was proposed and examined using D labeling experiments. A systematic study of the effects of the phenanthrene substitution pattern on the anticancer activity against three human cancer cell lines was discussed. PMID- 26836704 TI - Quantitative characterization and micro-CT mineral mapping of natural fissural enamel lesions. AB - OBJECTIVES: The aim of this study was to characterize the mineral distribution pattern of natural fissural enamel lesions and to quantify structural parameters and mineral density of these lesions in comparison to proximal white spot enamel lesions. METHODS: Imaging was undertaken using a high-resolution desktop micro computed tomography system. A calibration equation was used to transform the grey level values of images into true mineral density values. The value of lesion parameters including the mineral density and the thickness of the surface layer of the enamel lesion were extracted from mineral density profiles. RESULTS: The thickness of the surface layer showed variation among different lesions and it ranged from 0-90 MUm in proximal lesions and 0-137 MUm in fissural lesions. The average thickness of surface layer in fissural lesions was significantly higher than smooth surface proximal lesions. Sound fissural enamel showed lower mineral density compared to proximal enamel. CONCLUSION: Micro-CT and the suggested de noising and visualization method provide an efficient high-resolution approach for non-destructive evaluation of fissural lesions. Using these methods, the current study revealed the exclusive pattern and structure of fissural enamel lesions which may provide a basis for future studies on prevention and remineralization of these lesions. CLINICAL SIGNIFICANCE: The common demineralization pattern of fissural lesions, which indicates the extension of the lesion in two directions towards the pulp horns, may explain the early inflammation and symptoms of the pulp in fissural lesions even when the lesion base appears far from the pulp roof in normal radiographs. In addition, the presence of the surface layer, indicates that vigorous probing of the occlusal fissures may lead to breakage and cavitation of the enamel lesions. PMID- 26836705 TI - Identification and quantification of novel cranberry-derived plasma and urinary (poly)phenols. AB - Cranberries are a rich source of (poly)phenols, in particular proanthocyanidins, anthocyanins, flavonols, and phenolic acids. However, little is known about their bioavailability in humans. We investigated the absorption, metabolism, and excretion of cranberry (poly)phenols in plasma and urine of healthy young men after consumption of a cranberry juice (787 mg (poly)phenols). A total of 60 cranberry-derived phenolic metabolites were identified using UPLC-Q-TOF-MS analysis with authentic standards. These included sulfates of pyrogallol, valerolactone, benzoic acids, phenylacetic acids, glucuronides of flavonols, as well as sulfates and glucuronides of cinnamic acids. The most abundant plasma metabolites were small phenolic compounds, in particular hippuric acid, catechol O-sulfate, 2,3-dihydroxybenzoic acid, phenylacetic acid, isoferulic acid, 4 methylcatechol-O-sulfate, alpha-hydroxyhippuric acid, ferulic acid 4-O-sulfate, benzoic acid, 4-hydroxyphenyl acetic acid, dihydrocaffeic acid 3-O-sulfate, and vanillic acid-4-O-sulfate. Some benzoic acids, cinnamic acids, and flavonol metabolites appeared in plasma early, at 1-2 h post-consumption. Others such as phenylacetic acids, benzaldehydes, pyrogallols, catechols, hippuric and dihydrocinnamic acid derivatives appear in plasma later (Tmax 4-22 h). The 24 h urinary recovery with respect to the amount of (poly)phenols consumed was 6.2%. Our extensive description of the bioavailability of cranberry (poly)phenols lays important groundwork necessary to start understanding the fate of these compounds in humans. PMID- 26836706 TI - Other species in the aqueous environment of a peptide can invert its intrinsic solvated polyproline II/beta propensity: Implications for amyloid formation. AB - As we have previously shown, the predominance of the polyproline II conformation in the circular dichroism spectra of aqueous polypeptides is related to its lower energy than that of the beta conformation. To test whether this is still the case in the presence of additional components in the medium, we have calculated the energy difference between these two conformations in an alanine-dipeptide/12 water system without and with the addition of an HCl molecule. We find in the latter case that the beta conformer is of lower energy than the polyproline II. Energy profiles near the minima in both cases also permit conclusions about the relative entropies of these structures. These results emphasize the importance of considering the peptide-plus-medium state as the relevant entity in determining the structural properties of such systems. Such an inversion could be relevant to the formation of amyloid and could thus lead to new strategies for studying its role in the development of neurodegenerative diseases. (c) 2016 Wiley Periodicals, Inc. Biopolymers 105: 305-311, 2016. PMID- 26836707 TI - Formulation, physicochemical characterization and stability study of lithium loaded microemulsion system. AB - Lithium biocompatible microemulsion based on Peceol((r)), lecithin, ethanol and water was studied in attempt to identify the optimal compositions in term of drug content, physicochemical properties and stability. Lithium solubilization in microemulsion was found to be compatible with a drug-surfactant binding model. Lithium ions were predominantly solubilized within lecithin head group altering significantly the interfacial properties of the system. Pseudo-ternary phase diagrams of drug free and drug loaded microemulsions were built at constant ethanol/lecithin weight ratio (40/60). Lithium loaded microemulsion has totally disappeared in the Peceol((r)) rich part of phase diagram; critical fractions of lecithin and ethanol were required for the formation of stable microemulsion. The effect of lithium concentration on the properties and physical stability of microemulsions were studied using microscopy, Karl Fischer titrations, rheology analyses, conductivity measurements and centrifugation tests. The investigated microemulsions were found to be stable under accelerated storage conditions. The systems exhibited low viscosity and behaved as Newtonian fluid and no structural transition was shown. PMID- 26836708 TI - A new PAMPA model using an in-house brain lipid extract for screening the blood brain barrier permeability of drug candidates. AB - The determination of the permeability of drug candidates across the blood-brain barrier (BBB) is a fundamental step during drug discovery programs. The parallel artificial membrane permeability assay (PAMPA) is a high throughput screening tool applied to evaluate the passive permeability and adapted to predict BBB penetration. Herein, a new PAMPA model was developed using an in-house brain lipid extract capable of discriminating BBB permeable from non-permeable compounds. The apparent permeability (Papp) of 18 reference molecules and 10 test compounds was assessed and compared with phosphatidylcholine and commercial porcine polar brain lipid (PBL). The physicochemical selectivity of the in-house brain lipid extract was demonstrated by correlating Papp values with physicochemical properties and its predictive capacity estimated by establishing in vitro-in vivo correlations. The strong correlations achieved between 2% (w/v) in-house lipid extract and PBL for reference (r(2)=0.77) and test compounds (r(2)=0.94) support an equivalent discriminatory capacity and validate the presented model. Moreover, PAMPA studies performed with PBL and in-house lipid extract exhibited a higher correlation with the in vivo parameter logBB (r(2)=0.76 and r(2)=0.72, respectively) than phosphatidylcholine (r(2)=0.51). Overall, the applied lipid extraction process was reproducible, economical and provided lipid extracts that can be used to reliably assess BBB permeation. PMID- 26836709 TI - Synthesis and characterization of new composite materials based on poly(methacrylic acid) and hydroxyapatite with applications in dentistry. AB - The use of methacrylic acid (MAA) in medicine was poorly investigated in the past but can be of great importance because the incorporation of hydroxyapatite (HA) can lead to new composite materials with good properties due to the strong electrostatic interactions between carboxylate groups of polymer and Ca(2+) ions from HA. The scope of this study was to determine the potential of using composite materials based on poly(methacrylic acid) (PMAA) and hydroxyapatite in dentistry. Two routes of synthesis were taken into account: i) HA was synthesised in situ and ii) commercial HA was used. Fourier transform infrared spectroscopy and X-ray diffraction were used for compositional assessments. Scanning electron microscopy was performed to determine the morphology and differential thermal analysis (DTA) coupled with thermogravimetric analysis (TG) was used to study the thermal behaviour and to observe quantitative changes. In-vitro tests were also performed in order to evaluate the biocompatibility of both PMAA/HA composites by monitoring the development potential of human endothelial cells using MTT assay and fluorescent microscopy. PMID- 26836710 TI - A review of factors affecting electrostatic charging of pharmaceuticals and adhesive mixtures for inhalation. AB - Pharmaceutical powders are typically insulators consisting of relatively small particles and thus they usually exhibit significant electrostatic charging behaviours. In the inhalation field, the measurement of electrostatic charge is an imperative stage during pharmaceutical formulation development. The electrostatic charge is affected by the interplay of many factors. This article reviews the factors affecting the electrostatic charging of pharmaceutical powders with a focus on dry powder inhalations. The influences of particle resistivity, size distribution, shape distribution, surface roughness, polymorphic form and hygroscopicity, as well as the effects of moisture uptake, environmental conditions, pharmaceutical processing (i.e., milling, sieving, spray drying and blending), and storage on the electrostatic charge behaviours of pharmaceuticals, with focus on inhalation powders, were reviewed. The influence of electrostatic charge on the performance of dry powder inhaler formulations in terms of drug content homogeneity, the passage of drug through the inhaler device, drug-carrier adhesion/detachment, and drug deposition on the respiratory airways were discussed. The understanding gained is crucial to improving the safety, quality, and efficiency of the pharmaceutical inhalation products. PMID- 26836711 TI - Development of a novel dry powder inhalation formulation for the delivery of rivastigmine hydrogen tartrate. AB - The purpose of this study was to prepare engineered particles of rivastigmine hydrogen tartrate (RHT) and to characterize the physicochemical and aerodynamic properties, in comparison to a lactose carrier formulation (LCF). Microparticles were prepared from ethanol/water solutions containing RHT with and without the incorporation of L-leucine (Leu), using a spray dryer. Dry powder inhaler formulations prepared were characterized by scanning electron microscopy, powder X-ray diffraction, laser diffraction particle sizing, ATR-FTIR, differential scanning calorimetry, bulk and tapped density, dynamic vapour sorption and in vitro aerosol deposition behaviour using a next generation impactor. The smooth surfaced spherical morphology of the spray dried microparticles was altered by adding Leu, resulting in particles becoming increasingly wrinkled with increasing Leu. Powders presented low densities. The glass transition temperature was sufficiently high (>90 degrees C) to suggest good stability at room temperature. As Leu content increased, spray dried powders presented lower residual solvent content, lower particle size, higher fine particle fraction (FPF<5 MUm), and lower mass median aerodynamic diameter (MMAD). The LCF showed a lower FPF and higher MMAD, relative to the spray dried formulations containing more than 10% Leu. Spray dried RHT powders presented better aerodynamic properties, constituting a potential drug delivery system for oral inhalation. PMID- 26836712 TI - First Pass Success Without Hypoxemia Is Increased With the Use of Apneic Oxygenation During Rapid Sequence Intubation in the Emergency Department. AB - OBJECTIVES: The objective was to determine the effect of apneic oxygenation (AP OX) on first pass success without hypoxemia (FPS-H) in adult patients undergoing rapid sequence intubation (RSI) in the emergency department (ED). METHODS: Continuous quality improvement data were prospectively collected on all patients intubated in an academic ED from July 1, 2013, to June 30, 2015. During this period the use of AP OX was introduced and encouraged for all patients undergoing RSI in the ED. Following each intubation, the operator completed a standardized data form that included information on patient, operator, and intubation characteristics. Adult patients 18 years of age or greater who underwent RSI in the ED by emergency medicine residents were included in the analysis. The primary outcome was FPS-H, which was defined as successful tracheal intubation on a single laryngoscope insertion without oxygen saturation falling below 90%. A multivariate logistic regression analysis was performed to determine the effect of AP OX on FPS-H. RESULTS: During the 2-year study period, 635 patients met inclusion criteria. Of these, 380 (59.8%) had AP OX utilized and 255 (40.2%) had no AP OX utilized. In the AP OX cohort the FPS-H was 312/380 (82.1%) and in the no AP OX cohort the FPS-H was 176/255 (69.0%) (difference = 13.1%, 95% confidence interval [CI] = 6.2% to 19.9%). In the multivariate logistic regression analysis, the use of AP OX was associated with an increased odds of FPS-H (adjusted odds ratio = 2.2, 95% CI = 1.5 to 3.3). CONCLUSIONS: The use of AP OX during the RSI of adult patients in the ED was associated with a significant increase in FPS-H. These results suggest that the use of AP OX has the potential to increase the safety of RSI in the ED by reducing the number of intubation attempts and the incidence of hypoxemia. PMID- 26836716 TI - Symphony in Grey and Green: The Ocean: James McNeill Whistler. PMID- 26836717 TI - US Infant Mortality Rate Declines but Still Exceeds Other Developed Countries. PMID- 26836718 TI - 4 Simple Reforms to Address Mass Shootings and Other Firearm Violence. PMID- 26836726 TI - Academic Health Systems' Third Curve: Population Health Improvement. PMID- 26836727 TI - A PIECE OF MY MIND. My Body, Your Crime: The Anatomy of a Medical Note. PMID- 26836728 TI - Fish Consumption, Brain Mercury, and Neuropathology in Patients With Alzheimer Disease and Dementia. PMID- 26836729 TI - Effect of Subcutaneous Dupilumab on Nasal Polyp Burden in Patients With Chronic Sinusitis and Nasal Polyposis: A Randomized Clinical Trial. AB - IMPORTANCE: Dupilumab has demonstrated efficacy in patients with asthma and atopic dermatitis, which are both type 2 helper T-cell-mediated diseases. OBJECTIVE: To assess inhibition of interleukins 4 and 13 with dupilumab in patients with chronic sinusitis and nasal polyposis. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled parallel-group study conducted at 13 sites in the United States and Europe between August 2013 and August 2014 in 60 adults with chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids with 16 weeks of follow-up. INTERVENTIONS: Subcutaneous dupilumab (a 600 mg loading dose followed by 300 mg weekly; n = 30) or placebo (n = 30) plus mometasone furoate nasal spray for 16 weeks. MAIN OUTCOMES AND MEASURES: Change in endoscopic nasal polyp score (range, 0-8; higher scores indicate worse status) at 16 weeks (primary end point). Secondary end points included Lund-Mackay computed tomography (CT) score (range, 0-24; higher scores indicate worse status), 22-item SinoNasal Outcome Test score (range, 0 110; higher scores indicating worse quality of life; minimal clinically important difference >=8.90), sense of smell assessed using the University of Pennsylvania Smell Identification Test (UPSIT) score (range, 0-40; higher scores indicate better status), symptoms, and safety. RESULTS: Among the 60 patients who were randomized (mean [SD] age, 48.4 years [9.4 years]; 34 men [56.7%]; 35 with comorbid asthma), 51 completed the study. The least squares (LS) mean change in nasal polyp score was -0.3 (95% CI, -1.0 to 0.4) with placebo and -1.9 (95% CI, 2.5 to -1.2) with dupilumab (LS mean difference, -1.6 [95% CI, -2.4 to -0.7]; P < .001). The LS mean difference between the 2 groups for the Lund-Mackay CT total score was -8.8 (95% CI, -11.1 to -6.6; P < .001). Significant improvements with dupilumab were also observed for the 22-item SinoNasal Outcome Test (LS mean difference between groups, -18.1 [95% CI, -25.6 to -10.6]; P < .001) and sense of smell assessed by UPSIT (LS mean difference, 14.8 [95% CI, 10.9 to 18.7]; P < .001). The most common adverse events were nasopharyngitis (33% in the placebo group vs 47% in the dupilumab group), injection site reactions (7% vs 40%, respectively), and headache (17% vs 20%). CONCLUSIONS AND RELEVANCE: Among adults with symptomatic chronic sinusitis and nasal polyposis refractory to intranasal corticosteroids, the addition of subcutaneous dupilumab to mometasone furoate nasal spray compared with mometasone alone reduced endoscopic nasal polyp burden after 16 weeks. Further studies are needed to assess longer treatment duration, larger samples, and direct comparison with other medications. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01920893. PMID- 26836733 TI - Transcranial Magnetic Stimulation for Chronic Tinnitus. PMID- 26836730 TI - Effect of Acetazolamide vs Placebo on Duration of Invasive Mechanical Ventilation Among Patients With Chronic Obstructive Pulmonary Disease: A Randomized Clinical Trial. AB - IMPORTANCE: Acetazolamide has been used for decades as a respiratory stimulant for patients with chronic obstructive pulmonary disease (COPD) and metabolic alkalosis, but no large randomized placebo-controlled trial is available to confirm this approach. OBJECTIVE: To determine whether acetazolamide reduces mechanical ventilation duration in critically ill patients with COPD and metabolic alkalosis. DESIGN, SETTING, AND PARTICIPANTS: The DIABOLO study, a randomized, double-blind, multicenter trial, was conducted from October 2011 through July 2014 in 15 intensive care units (ICUs) in France. A total of 382 patients with COPD who were expected to receive mechanical ventilation for more 24 hours were randomized to the acetazolamide or placebo group and 380 were included in an intention-to treat analysis. INTERVENTIONS: Acetazolamide (500 1000 mg, twice daily) vs placebo administered intravenously in cases of pure or mixed metabolic alkalosis, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome was the duration of invasive mechanical ventilation via endotracheal intubation or tracheotomy. Secondary outcomes included changes in arterial blood gas and respiratory parameters, weaning duration, adverse events, use of noninvasive ventilation after extubation, successful weaning, the duration of ICU stay, and in-ICU mortality. RESULTS: Among 382 randomized patients, 380 (mean age, 69 years; 272 men [71.6%]; 379 [99.7%] with endotracheal intubation) completed the study. For the acetazolamide group (n = 187), compared with the placebo group (n = 193), no significant between-group differences were found for median duration of mechanical ventilation (-16.0 hours; 95% CI, -36.5 to 4.0 hours; P = .17), duration of weaning off mechanical ventilation (-0.9 hours; 95% CI, -4.3 to 1.3 hours; P = .36), daily changes of minute-ventilation ( 0.0 L/min; 95% CI, -0.2 to 0.2 L/min; P = .72), or partial carbon-dioxide pressure in arterial blood (-0.3 mm Hg; 95% CI, -0.8 to 0.2 mm Hg; P = .25), although daily changes of serum bicarbonate (between-group difference, -0.8 mEq/L; 95% CI, -1.2 to -0.5 mEq/L; P < .001) and number of days with metabolic alkalosis (between-group difference, -1; 95% CI, -2 to -1 days; P < .001) decreased significantly more in the acetazolamide group. Other secondary outcomes also did not differ significantly between groups. CONCLUSIONS AND RELEVANCE: Among patients with COPD receiving invasive mechanical ventilation, the use of acetazolamide, compared with placebo, did not result in a statistically significant reduction in the duration of invasive mechanical ventilation. However, the magnitude of the difference was clinically important, and it is possible that the study was underpowered to establish statistical significance. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01627639. PMID- 26836734 TI - Well-Demarcated, Scaly Plaques. PMID- 26836731 TI - Association of Seafood Consumption, Brain Mercury Level, and APOE epsilon4 Status With Brain Neuropathology in Older Adults. AB - IMPORTANCE: Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern. OBJECTIVE: To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumption or brain mercury levels are correlated with brain neuropathologies. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional analyses of deceased participants in the Memory and Aging Project clinical neuropathological cohort study, 2004-2013. Participants resided in Chicago retirement communities and subsidized housing. The study included 286 autopsied brains of 554 deceased participants (51.6%). The mean (SD) age at death was 89.9 (6.1) years, 67% (193) were women, and the mean (SD) educational attainment was 14.6 (2.7) years. EXPOSURES: Seafood intake was first measured by a food frequency questionnaire at a mean of 4.5 years before death. MAIN OUTCOMES AND MEASURES: Dementia-related pathologies assessed were Alzheimer disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. Dietary consumption of seafood and n-3 fatty acids was annually assessed by a food frequency questionnaire in the years before death. Tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses. RESULTS: Among the 286 autopsied brains of 544 participants, brain mercury levels were positively correlated with the number of seafood meals consumed per week (rho = 0.16; P = .02). In models adjusted for age, sex, education, and total energy intake, seafood consumption (>= 1 meal[s]/week) was significantly correlated with less Alzheimer disease pathology including lower density of neuritic plaques (beta = -0.69 score units [95% CI, -1.34 to -0.04]), less severe and widespread neurofibrillary tangles (beta = -0.77 score units [95% CI, -1.52 to -0.02]), and lower neuropathologically defined Alzheimer disease (beta = -0.53 score units [95% CI, -0.96 to -0.10]) but only among apolipoprotein E (APOE epsilon4) carriers. Higher intake levels of alpha-linolenic acid (18:3 n-3) were correlated with lower odds of cerebral macroinfarctions (odds ratio for tertiles 3 vs 1, 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation had no statistically significant correlation with any neuropathologic marker. Higher brain concentrations of mercury were not significantly correlated with increased levels of brain neuropathology. CONCLUSIONS AND RELEVANCE: In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology. PMID- 26836732 TI - Association Between Expiratory Central Airway Collapse and Respiratory Outcomes Among Smokers. AB - IMPORTANCE: Central airway collapse greater than 50% of luminal area during exhalation (expiratory central airway collapse [ECAC]) is associated with cigarette smoking and chronic obstructive pulmonary disease (COPD). However, its prevalence and clinical significance are unknown. OBJECTIVE: To determine whether ECAC is associated with respiratory morbidity in smokers independent of underlying lung disease. DESIGN, SETTING, AND PARTICIPANTS: Analysis of paired inspiratory-expiratory computed tomography images from a large multicenter study (COPDGene) of current and former smokers from 21 clinical centers across the United States. Participants were enrolled from January 2008 to June 2011 and followed up longitudinally until October 2014. Images were initially screened using a quantitative method to detect at least a 30% reduction in minor axis tracheal diameter from inspiration to end-expiration. From this sample of screen positive scans, cross-sectional area of the trachea was measured manually at 3 predetermined levels (aortic arch, carina, and bronchus intermedius) to confirm ECAC (>50% reduction in cross-sectional area). EXPOSURES: Expiratory central airway collapse. MAIN OUTCOMES AND MEASURES: The primary outcome was baseline respiratory quality of life (St George's Respiratory Questionnaire [SGRQ] scale 0 to 100; 100 represents worst health status; minimum clinically important difference [MCID], 4 units). Secondary outcomes were baseline measures of dyspnea (modified Medical Research Council [mMRC] scale 0 to 4; 4 represents worse dyspnea; MCID, 0.7 units), baseline 6-minute walk distance (MCID, 30 m), and exacerbation frequency (events per 100 person-years) on longitudinal follow-up. RESULTS: The study included 8820 participants with and without COPD (mean age, 59.7 [SD, 6.9] years; 4667 [56.7%] men; 4559 [51.7%] active smokers). The prevalence of ECAC was 5% (443 cases). Patients with ECAC compared with those without ECAC had worse SGRQ scores (30.9 vs 26.5 units; P < .001; absolute difference, 4.4 [95% CI, 2.2-6.6]) and mMRC scale scores (median, 2 [interquartile range [IQR], 0-3]) vs 1 [IQR, 0-3]; P < .001]), but no significant difference in 6-minute walk distance (399 vs 417 m; absolute difference, 18 m [95% CI, 6-30]; P = .30), after adjustment for age, sex, race, body mass index, forced expiratory volume in the first second, pack-years of smoking, and emphysema. On follow-up (median, 4.3 [IQR, 3.2-4.9] years), participants with ECAC had increased frequency of total exacerbations (58 vs 35 events per 100 person-years; incidence rate ratio [IRR], 1.49 [95% CI, 1.29-1.72]; P < .001) and severe exacerbations requiring hospitalization (17 vs 10 events per 100 person years; IRR, 1.83 [95% CI, 1.51-2.21]; P < .001). CONCLUSIONS AND RELEVANCE: In a cross-sectional analysis of current and former smokers, the presence of ECAC was associated with worse respiratory quality of life. Further studies are needed to assess long-term associations with clinical outcomes. PMID- 26836735 TI - Drugs Past Their Expiration Date. PMID- 26836736 TI - Prevalence and Cost of Office Visits Prior to Colonoscopy for Colon Cancer Screening. PMID- 26836737 TI - Oral Nutrient Supplementation and Cognitive Function. PMID- 26836738 TI - Oral Nutrient Supplementation and Cognitive Function. PMID- 26836739 TI - Oral Nutrient Supplementation and Cognitive Function--Reply. PMID- 26836740 TI - Accounting for Missing Data in Clinical Research. PMID- 26836741 TI - Incorrect Spelling of an Author's Name. PMID- 26836742 TI - Incorrect I2 Value in the Table. PMID- 26836743 TI - Accounting for Missing Data in Clinical Research--Reply. PMID- 26836745 TI - Narration: Timelessness. PMID- 26836746 TI - JAMA PATIENT PAGE. Dietary Guidelines for Americans. PMID- 26836748 TI - A P-H Functionalized Al/P Frustrated Lewis Pair: Substrate Activation and Selective Hydrogen Transfer. AB - Hydroalumination of an alkynylphosphine gave an unprecedented P-H functionalized frustrated Lewis pair (FLP). The reactive P-H group does not influence the typical FLP properties, but the activation of substrates follows a new reaction pattern involving hydrogen transfer to yield unusual compounds with phosphaurea, iminophosphine, or phosphanyltriazene structural motifs. PMID- 26836747 TI - Nickel titanium springs versus stainless steel springs: A randomized clinical trial of two methods of space closure. AB - OBJECTIVE: To compare the clinical performance of nickel titanium (NiTi) versus stainless steel (SS) springs during orthodontic space closure. DESIGN: Two-centre parallel group randomized clinical trial. SETTING: Orthodontic Department University of Manchester Dental Hospital and Orthodontic Department Countess of Chester Hospital, United Kingdom. SUBJECTS AND METHODS: Forty orthodontic patients requiring fixed appliance treatment were enrolled, each being randomly allocated into either NiTi (n = 19) or SS groups (n = 21). Study models were constructed at the start of the space closure phase (T0) and following the completion of space closure (T1). The rate of space closure achieved for each patient was calculated by taking an average measurement from the tip of the canine to the mesiobuccal groove on the first permanent molar of each quadrant. RESULTS: The study was terminated early due to time constraints. Only 30 patients completed, 15 in each study group. There was no statistically significant difference between the amounts of space closed (mean difference 0.17 mm (95%CI 0.99 to 1.34; P = 0.76)). The mean rate of space closure for NiTi coil springs was 0.58 mm/4 weeks (SD 0.24) and 0.85 mm/4 weeks (SD 0.36) for the stainless steel springs. There was a statistically significant difference between the two groups (P = 0.024), in favour of the stainless steel springs, when the mean values per patient were compared. CONCLUSIONS: Our study shows that stainless steel springs are clinically effective; these springs produce as much space closure as their more expensive rivals, the NiTi springs. PMID- 26836749 TI - Exactly solvable spin-1 Ising-Heisenberg diamond chain with the second-neighbor interaction between nodal spins. AB - The spin-1 Ising-Heisenberg diamond chain with the second-neighbor interaction between nodal spins is rigorously solved using the transfer-matrix method. In particular, exact results for the ground state, magnetization process and specific heat are presented and discussed. It is shown that further-neighbor interaction between nodal spins gives rise to three novel ground states with a translationally broken symmetry, but at the same time, does not increases the total number of intermediate plateaus in a zero-temperature magnetization curve compared with the simplified model without this interaction term. The zero-field specific heat displays interesting thermal dependencies with a single- or double peak structure. PMID- 26836750 TI - Impact of Na Dynamics at the Cu2ZnSn(S,Se)4/CdS Interface During Post Low Temperature Treatment of Absorbers. AB - Cu2SnZn(S,Se)4 (CZTSSe) solar cells based on earth abundant and nontoxic elements currently achieve efficiencies exceeding 12%. It has been reported that, to obtain high efficiency devices, a post thermal treatment of absorbers or devices at temperatures ranging between 150 and 400 degrees C (post low temperature treatment, PLTT) is advisable. Recent findings point toward a beneficial passivation of grain boundaries with SnOx or Cu-depleted surface and grain boundaries during the PLTT process, but no investigation regarding alkali doping is available, even though alkali dynamics, especially Na, are systematically reported to be crucial within the field. In this work, CZTSSe absorbers were subjected to the PLTT process under different temperatures, and solar cells were completed. We found surprisingly behavior in which efficiency decreased to nearly 0% at 200 degrees C during the PLTT process, being recovered or even improved at temperatures above 300 degrees C. This unusual behavior correlates well with the Na dynamics in the devices, especially with the in-depth distribution of Na in the active CZTSSe/CdS interface region, indicating the key importance of Na spatial distribution on device properties. We present an innovative model for Na dynamics supported by theoretical calculations and additional specially designed experiments to explain this behavior. After optimization of the PLTT process, a Se-rich CZTSSe solar cell with 8.3% efficiency was achieved. PMID- 26836751 TI - Proteomics and HIV. PMID- 26836754 TI - Hub and spoke model: making rural healthcare in India affordable, available and accessible. AB - CONTEXT: Quality health care should be within everyone's reach, especially in a developing country. While India has the largest private health sector in the world, only one-fifth of healthcare expenditure is publically financed; it is mostly an out-of-pocket expense. About 70% of Indians live in rural areas making about $3 per day, and a major portion of that goes towards food and shelter and, thus, not towards health care. Transportation facilities in rural India are poor, making access to medical facilities difficult, and infrastructure facilities are minimal, making the available medical care insufficient. The challenge presented to India was to provide health care that was accessible, available and affordable to people in rural areas and the low-income bracket. ISSUES: The intent of this article is to determine whether the hub and spoke model (HSM), when implemented in the healthcare industry, can expand the market reach and increase profits while reducing costs of operations for organizations and, thereby, cost to customers. This article also discusses the importance of information and communications technologies (ICT) in the HSM approach, which the handful of published articles in this topic have failed to discuss. This article opts for an exploratory study, including review of published literature, web articles, viewpoints of industry experts, published journals, and in-depth interviews. This article will discuss how and why the HSM works in India's healthcare industry while isolating its strengths and weaknesses, and analyzing the impact of India's success. India's HSM implementation has become a paramount example of an acceptable model that, while exceeding the needs and expectations of its patients, is cost-effective and has obtained operational and health-driven results. Despite being an emerging nation, India takes the top spot in terms of affordability of ICT as well as for having the highest number of computer literate graduates and healthcare workers in the world. These factors further aid the implementation of HSM in India, thereby proving the model as a stable operational environment that is saving costs in a financially challenged nation. LESSONS LEARNED: HSM has an innovative architecture that emphasizes optimal utilization of scarce healthcare resources in rural areas. HSM demonstrates that medical care can be provided to even the most rural areas while still utilizing modern procedures and equipment at a much more nominal cost to the end user. It also eliminates the need for unnecessary travel, and keeps costs low to medical facilities and patients alike. The model has the potential to create and sustain thousands of local jobs, both direct and indirect. The hope is that the review of the impact of the HSM in Indian health care will result in inquiries of a similar nature in the future. PMID- 26836756 TI - Is hepatitis C virus eradication a realistic objective in the absence of a prophylactic vaccine? PMID- 26836755 TI - Examination of Glycosaminoglycan Binding Sites on the XCL1 Dimer. AB - Known for its distinct metamorphic behavior, XCL1 interconverts between a canonical chemokine folded monomer (XCL1mon) that interacts with the receptor, XCR1, and a unique dimer (XCL1dim) that interacts with glycosaminoglycans and inhibits HIV-1 activity. This study presents the first detailed analysis of the GAG binding properties of XCL1dim. Basic residues within a conformationally selective dimeric variant of XCL1 (W55D) were mutated and analyzed for their effects on heparin binding. Mutation of Arg23 and Arg43 greatly diminished the level of heparin binding in both heparin Sepharose chromatography and surface plasmon resonance assays. To assess the contributions of different GAG structures to XCL1 binding, we developed a solution fluorescence polarization assay and correlated affinity with the length and level of sulfation of heparan sulfate oligosaccharides. It was recently demonstrated that the XCL1 GAG binding form, XCL1dim, is responsible for preventing HIV-1 infection through interactions with gp120. This study defines a GAG binding surface on XCL1dim that includes residues that are important for HIV-1 inhibition. PMID- 26836757 TI - Elastic poly(epsilon-caprolactone)-polydimethylsiloxane copolymer fibers with shape memory effect for bone tissue engineering. AB - A porous shape memory scaffold with biomimetic architecture is highly promising for bone tissue engineering applications. In this study, a series of new shape memory polyurethanes consisting of organic poly(epsilon-caprolactone) (PCL) segments and inorganic polydimethylsiloxane (PDMS) segments in different ratios (9 : 1, 8 : 2 and 7 : 3) was synthesised. These PCL-PDMS copolymers were further engineered into porous fibrous scaffolds by electrospinning. With different ratios of PCL: PDMS, the fibers showed various fiber diameters, thermal behaviour and mechanical properties. Even after being processed into fibrous structures, these PCL-PDMS copolymers maintained their shape memory properties, and all the fibers exhibited excellent shape recovery ratios of >90% and shape fixity ratios of >92% after 7 thermo-mechanical cycles. Biological assay results corroborated that the fibrous PCL-PDMS scaffolds were biocompatible by promoting osteoblast proliferation, functionally enhanced biomineralization-relevant alkaline phosphatase expression and mineral deposition. Our study demonstrated that the PCL-PDMS fibers with excellent shape memory properties are promising substrates as bioengineered grafts for bone regeneration. PMID- 26836758 TI - The genetic consequences of selection in natural populations. AB - The selection coefficient, s, quantifies the strength of selection acting on a genetic variant. Despite this parameter's central importance to population genetic models, until recently we have known relatively little about the value of s in natural populations. With the development of molecular genetic techniques in the late 20th century and the sequencing technologies that followed, biologists are now able to identify genetic variants and directly relate them to organismal fitness. We reviewed the literature for published estimates of natural selection acting at the genetic level and found over 3000 estimates of selection coefficients from 79 studies. Selection coefficients were roughly exponentially distributed, suggesting that the impact of selection at the genetic level is generally weak but can occasionally be quite strong. We used both nonparametric statistics and formal random-effects meta-analysis to determine how selection varies across biological and methodological categories. Selection was stronger when measured over shorter timescales, with the mean magnitude of s greatest for studies that measured selection within a single generation. Our analyses found conflicting trends when considering how selection varies with the genetic scale (e.g., SNPs or haplotypes) at which it is measured, suggesting a need for further research. Besides these quantitative conclusions, we highlight key issues in the calculation, interpretation, and reporting of selection coefficients and provide recommendations for future research. PMID- 26836759 TI - Two-Dimensional Infrared Study of (13)C-Natural Abundant Vibrational Transition Reveals Intramolecular Vibrational Redistribution Rather than Fluxional Exchange in Mn(CO)5Br. AB - In this work, molecular-symmetry enhanced (13)CO natural abundant isotopic infrared transition was identified in Mn(CO)5Br dissolved in CCl4 by FTIR spectroscopy. Diagonal and associated off-diagonal two-dimensional IR (2D IR) peaks of the (13)CO-species were found to be spectrally separated from the all (12)CO species, allowing a direct probe of the (13)C natural abundant ensemble. Temperature-dependent FTIR experiment showed no evidence of ligand exchange in the metal carbonyl complex. Intramolecular vibrational redistribution dynamics among the CO stretching vibrational states were extracted using population-time dependent 2D IR diagonal and off-diagonal peaks for both radial mono-(13)CO and all-(12)CO isotopomers. This work demonstrates the potential use of natural abundant isotopic molecular species as a probe for revealing equilibrium and nonequilibrium structural dynamics in condensed-phase molecular systems. PMID- 26836760 TI - Scale dependency in effectiveness, isolation, and social-ecological spillover of protected areas. AB - Protected areas are considered vital for the conservation of biodiversity. Given their central role in many conservation strategies, it is important to know whether they adequately protect biodiversity within their boundaries; whether they are becoming more isolated from other natural areas over time; and whether they play a role in facilitating or reducing land-cover change in their surroundings. We used matching methods and national and local analyses of land cover change to evaluate the combined effectiveness (i.e., avoided natural-cover loss), isolation (i.e., changes in adjacent areas), and spillover effects (i.e., impacts on adjacent areas) of 19 national parks in South Africa from 2000 to 2009. All parks had either similar or lower rates of natural-cover loss than matched control samples. On a national level, mean net loss of natural cover and mean net gain of cultivation cover decreased with distance from park boundary, but there was considerable variation in trends around individual parks, providing evidence for both increased isolation and buffering of protected areas. Fourteen parks had significant positive spillover and reduced natural-cover loss in their surroundings, whereas five parks experienced elevated levels of natural-cover loss. Conclusions about social-ecological spillover effects from protected areas depended heavily on the measures of land-cover change used and the scale at which the results were aggregated. Our findings emphasize the need for high-resolution data when assessing spatially explicit phenomena such as land-cover change and challenge the usefulness of large-scale (coarse grain, broad extent) studies for understanding social-ecological dynamics around protected areas. PMID- 26836761 TI - EDITOR'S NOTE. PMID- 26836764 TI - Highly Regio- and Stereoselective Intermolecular Seleno- and Thioamination of Alkynes. AB - By using N-fluorobenzenesulfonimide as both the oxidant and the amination reagent, we have realized the first example of the intermolecular chalcogenative amination of alkynes, which grants facile, highly regio- and stereoselective access to chalcogenated enamides. The reaction features mild conditions, high yields and selectivities, remarkably broad substrate scope, and excellent functional group tolerance. Mechanistic studies indicate the in situ generated chalcogen imidates to be the actual reactive species, which in turn, has clarified the mechanism of related transformations. These reactions represent significant additions to the development of the highly selective amino bisfunctionalization of alkynes. PMID- 26836763 TI - A comparative study on active and passive epidemiological surveillance for dengue in five countries of Latin America. AB - BACKGROUND: Dengue is a notifiable infectious disease in many countries, but under-reporting of cases to National Epidemiological Surveillance Systems (NESSs) conceals the true extent of the disease burden. The incidence of dengue identified in a cohort study was compared with those reported to NESSs. METHODS: A randomized, placebo-controlled study was undertaken in Brazil, Colombia, Honduras, Mexico, and Puerto Rico to assess the efficacy of a tetravalent dengue vaccine (CYD-TDV) in children aged 9-16 years. The incidence of dengue in the placebo group was compared with that reported to NESSs in a similar age group (10 19 years) from June 2011 to April 2014. RESULTS: Three thousand six hundred and fifteen suspected dengue cases were identified in the study over 13527 person years of observation. The overall incidence of confirmed dengue was 2.9 per 100 person-years (range 1.5 to 4.1 per 100 person-years). In the NESSs combined, over 3.2 million suspected dengue cases were reported during the same period, corresponding to over 1 billion person-years of observation. The incidence of confirmed dengue reported by the NESSs in the same locality where the study took place was 0.286 per 100 person-years across Brazil, Colombia, and Mexico (range 0.180 to 0.734 per 100 person-years). The incidence of confirmed dengue was 10.0 fold higher in the study than that reported to NESSs in the same localities (range 3.5- to 19.4-fold higher). CONCLUSIONS: There is a substantial under reporting of dengue in the NESSs. Understanding the level of under-reporting would allow more accurate estimates of the dengue burden in Latin America. PMID- 26836765 TI - Repair of rabbit cartilage defect based on the fusion of rabbit bone marrow stromal cells and Nano-HA/PLLA composite material. AB - Objective To assess the effect of the fusion of rabbit bone marrow stromal cells (rBMSCs) and Nano-hydroxyapatite/poly (l-lactic acid) (Nano-HA/PLLA) in repairing the rabbit knee joint with full-thickness cartilage defect. Method The rBMSCs were isolated and cultured in vitro, and the third generation of rBMSCs was co cultured with the Nano-HA/PLLA to construct the tissue-engineered cartilage (TEC). Eighteen New Zealand white rabbits were selected and randomly divided into three groups, namely, TEC group, Nano-HA/PLLA group, and control group. A cartilage defect model with the diameter of 4.5 mm and depth of 5 mm was constructed on the articular surface of medial malleolus of rabbit femur. General observation, histological observation, and Wakitani's histological scoring were conducted in the 12th and 24th week postoperatively. Results The results of TEC group indicated that new cartilage tissue was formed on the defect site and subchondral bone achieved physiological integration basically. Histological and immunohistochemical analyses indicated the generation of massive extracellular matrix. In contrast, limited regeneration and reconstruction of cartilage was achieved in the Nano-HA/PLLA group and control group, with a significant difference from the TEC group (p < 0.05). Moreover, the effect of cartilage repair was positively correlated with time. Conclusion The porous Nano-HA/PLLA combined with BMSCs promoted the repair of weight-bearing bone of adult rabbit's knee joint with cartilage defect. PMID- 26836767 TI - Revisiting the neural role of estrogen receptor beta in male sexual behavior by conditional mutagenesis. AB - Estradiol derived from neural aromatization of gonadal testosterone plays a key role in the perinatal organization of the neural circuitry underlying male sexual behavior. The aim of this study was to investigate the contribution of neural estrogen receptor (ER) beta in estradiol-induced effects without interfering with its peripheral functions. For this purpose, male mice lacking ERbeta in the nervous system were generated. Analyses of males in two consecutive tests with a time interval of two weeks showed an effect of experience, but not of genotype, on the latencies to the first mount, intromission, pelvic thrusting and ejaculation. Similarly, there was an effect of experience, but not of genotype, on the number of thrusts and mating length. Neural ERbeta deletion had no effect on the ability of males to adopt a lordosis posture in response to male mounts, after castration and priming with estradiol and progesterone. Indeed, only low percentages of both genotypes exhibited a low lordosis quotient. It also did not affect their olfactory preference. Quantification of tyrosine hydroxylase- and kisspeptin-immunoreactive neurons in the preoptic area showed unaffected sexual dimorphism of both populations in mutants. By contrast, the number of androgen receptor- and ERalpha-immunoreactive cells was significantly increased in the bed nucleus of stria terminalis of mutant males. These data show that neural ERbeta does not play a crucial role in the organization and activation of the neural circuitry underlying male sexual behavior. These discrepancies with the phenotype of global ERbeta knockout models are discussed. PMID- 26836768 TI - Inhibition of p38 pathway-dependent MPTP-induced dopaminergic neurodegeneration in estrogen receptor alpha knockout mice. AB - Approximately, 7-10 million people in the world suffer from Parkinson's disease (PD). Recently, increasing evidence has suggested the protective effect of estrogens against nigrostriatal dopaminergic damage in PD. In this study, we investigated whether estrogen affects 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-induced behavioral impairment in estrogen receptor alpha (ERalpha)-deficient mice. MPTP (15mg/kg, four times with 1.5-h interval) induced dopaminergic neurodegeneration was evaluated in ERalpha wild-type (WT) and knockout (KO) mice. Larger dopamine depletion, behavioral impairments (Rotarod test, Pole test, and Gait test), activation of microglia and astrocytes, and neuroinflammation after MPTP injection were observed in ERalpha KO mice compared to those in WT mice. Immunostaining for tyrosine hydroxylase (TH) after MPTP injection showed fewer TH-positive neurons in ERalpha KO mice than WT mice. Levels of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC, metabolite of dopamine) were also lowered in ERalpha KO mice after MPTP injection. Interestingly, a higher immunoreactivity for monoamine oxidase (MAO) B was found in the substantia nigra and striatum of ERalpha KO mice after MPTP injection. We also found an increased activation of p38 kinase (which positively regulates MAO B expression) in ERalpha KO mice. In vitro estrogen treatment inhibited neuroinflammation in 1-methyl-4-phenyl pyridium (MPP+)-treated cultured astrocyte cells; however, these inhibitory effects were removed by p38 inhibitor. These results indicate that ERalpha might be important for dopaminergic neuronal survival through inhibition of p38 pathway. PMID- 26836766 TI - Norovirus vaccines: Correlates of protection, challenges and limitations. AB - Norovirus (NoV) is responsible for at least 50% of all gastroenteritis outbreaks worldwide. NoVs are classified into 6 different genogroups (GGI- GGVI) based on the viral capsid protein with NoV genogroup II genotype 4 (GII.4) being the predominant strain causing human diseases. Supportive therapy involving reversal of dehydration and electrolyte deficiency is the main treatment of NoV gastroenteritis. However, the worldwide increased recognition of NoV as an important agent of diarrheal gastroenteritis prompted researchers to focus on establishing preventive strategies conferring long-lasting immunity. This review describes the current status of animal and human vaccine models/studies targeting NoV and addresses the factors hampering the development of a broadly effective vaccine. PMID- 26836769 TI - Oxytocin is associated with infant-care behavior and motivation in cooperatively breeding marmoset monkeys. AB - The neurohormone oxytocin (OT) is positively involved in the regulation of parenting and social bonding in mammals, and may thus also be important for the mediation of alloparental care. In cooperatively breeding marmosets, infants are raised in teamwork by parents and adult and sub-adult non-reproductive helpers (usually older siblings). Despite high intrinsic motivation, which may be mediated by hormonal priming, not all individuals are always equally able to contribute to infant-care due to competition among care-takers. Among the various care-taking behaviors, proactive food sharing may reflect motivational levels best, since it can be performed ad libitum by several individuals even if competition among surplus care-takers constrains access to infants. Our aim was to study the link between urinary OT levels and care-taking behaviors in group living marmosets, while taking affiliation with other adults and infant age into account. Over eight reproductive cycles, 26 individuals were monitored for urinary baseline OT, care-taking behaviors (baby-licking, -grooming, -carrying, and proactive food sharing), and adult-directed affiliation. Mean OT levels were generally highest in female breeders and OT increased significantly in all individuals after birth. During early infancy, high urinary OT levels were associated with increased infant-licking but low levels of adult-affiliation, and during late infancy, with increased proactive food sharing. Our results show that, in marmoset parents and alloparents, OT is positively involved in the regulation of care-taking, thereby reflecting the changing needs during infant development. This particularly included behaviors that are more likely to reflect intrinsic care motivation, suggesting a positive link between OT and motivational regulation of infant-care. PMID- 26836770 TI - Yolk testosterone affects growth and promotes individual-level consistency in behavioral lateralization of yellow-legged gull chicks. AB - Behavioral lateralization is common in animals and may be expressed at the individual- and at the population-level. The ontogenetic processes that control lateralization, however, are largely unknown. Well-established sex-dependence in androgen physiology and sex-dependent variation in lateralization have led to the hypothesis that testosterone (T) has organizational effects on lateralization. The effects of T exposure in early life on lateralization can be efficiently investigated by manipulating T levels in the cleidoic eggs of birds, because the embryo is isolated from maternal and sibling physiological interference, but this approach has been adopted very rarely. In the yellow-legged gull (Larus michahellis) we increased yolk T concentration within the physiological limits and tested the effects on the direction of lateralization in two functionally fundamental behaviors (begging for parental care and escape to cover) of molecularly sexed hatchlings. We also speculated that T may intervene in regulating consistency, rather than direction of lateralization, and therefore tested if T affected the 'repeatability' of lateral preference in consecutive behavioral trials. T treatment had no effect on the direction of lateralization, but enhanced the consistency of lateral preference in escape responses. Sex did not predict lateralization. Neither behavior was lateralized at the population level. We therefore showed for the first time in any species an effect of egg T on consistency in lateralization. The implications of the effect of T for the evolution of trade-offs in maternal allocation of egg hormones, and the evolutionary interpretations of findings from our studies on lateralization among unmanipulated birds are discussed. PMID- 26836771 TI - A potential mate influences reproductive development in female, but not male, pine siskins. AB - The role of photoperiod in avian reproductive timing has been well studied, and we are increasingly recognizing the roles of other environmental cues such as social cues. However, few studies have evaluated the extent to which males and females of the same species respond similarly to the same type of cue. Moreover, previous studies have rarely examined how variation in the quality or nature of a given social cue might modulate its effect. Here, we examine the sensitivity of male and female pine siskins (Spinus pinus) to a potential mate as a stimulatory cue for gonadal recrudescence, and we investigate whether variation in the relationship between a bird and its potential mate modulates the effect of that potential mate. Birds were initially housed without opposite sex birds on a 12L:12D photoperiod with ad libitum food. After gonadal recrudescence had begun males and females were randomly paired with an opposite sex bird or housed alone. An additional group of males was paired with estradiol-implanted females. In males, these social treatments had no effect on testis length, cloacal protuberance length, luteinizing hormone (LH) levels, or testosterone levels. In females, presence of a potential mate had a significant and positive effect on ovary score, defeathering of the brood patch, and LH levels. Among paired birds, the degree of affiliation within a pair corresponded to the extent of reproductive development in females, but not males. Thus, reproductive timing in females appears to be sensitive to both the presence of a potential mate and her relationship with him. PMID- 26836773 TI - Cortisol and testosterone associations with social network dynamics. AB - This study integrates behavioral endocrinology and network science to explore links between hormones and social network dynamics. Specifically, we examine how cortisol (C) and testosterone (T) are associated with creation of new friendships and maintenance of existing friendships. A collegiate marching band was used as a model system of a mixed-sex social organization. Participants (n=193; 53% female; M age=19.4years, 62.1% European-American) provided friendship nominations at time 1 and two months later at time 2. At time 1, participants donated saliva before and after rehearsal (later assayed for C and T). Stochastic actor-based models revealed that individuals with higher C levels were less likely to maintain their social relationships and more likely to create new friendships. In contrast, individuals with higher T levels were more likely to maintain friendships and less likely to create new relationships. Findings suggest that individual differences in C and T are associated with the initiation and maintenance of friendships and have several noteworthy theoretical implications. PMID- 26836774 TI - Mutated form (G52E) of inactive diphtheria toxin CRM197: molecular simulations clearly display effect of the mutation to NAD binding. AB - Mutated form (G52E) of diphtheria toxin (DT) CRM197 is an inactive and nontoxic enzyme. Here, we provided a molecular insight using comparative molecular dynamics (MD) simulations to clarify the influence of a single point mutation on overall protein and active-site loop. Post-processing MD analysis (i.e. stability, principal component analysis, hydrogen-bond occupancy, etc.) is carried out on both wild and mutated targets to investigate and to better understand the mechanistic differences of structural and dynamical properties on an atomic scale especially at nicotinamide adenine dinucleotide (NAD) binding site when a single mutation (G52E) happens at the DT. In addition, a docking simulation is performed for wild and mutated forms. The docking scoring analysis and docking poses results revealed that mutant form is not able to properly accommodate the NAD molecule. PMID- 26836772 TI - Oxytocin promotes functional coupling between paraventricular nucleus and both sympathetic and parasympathetic cardioregulatory nuclei. AB - The neuropeptide oxytocin (OXT) facilitates prosocial behavior and selective sociality. In the context of stress, OXT also can down-regulate hypothalamic pituitary-adrenal (HPA) axis activity, leading to consideration of OXT as a potential treatment for many socioaffective disorders. However, the mechanisms through which administration of exogenous OXT modulates social behavior in stressful environmental contexts are not fully understood. Here, we investigate the hypothesis that autonomic pathways are components of the mechanisms through which OXT aids the recruitment of social resources in stressful contexts that may elicit mobilized behavioral responses. Female prairie voles (Microtus ochrogaster) underwent a stressor (walking in shallow water) following pretreatment with intraperitoneal OXT (0.25mg/kg) or OXT antagonist (OXT-A, 20mg/kg), and were allowed to recover with or without their sibling cagemate. Administration of OXT resulted in elevated OXT concentrations in plasma, but did not dampen the HPA axis response to a stressor. However, OXT, but not OXT-A, pretreatment prevented the functional coupling, usually seen in the absence of OXT, between paraventricular nucleus (PVN) activity as measured by c-Fos immunoreactivity and HPA output (i.e. corticosterone release). Furthermore, OXT pretreatment resulted in functional coupling between PVN activity and brain regions regulating both sympathetic (i.e. rostral ventrolateral medulla) and parasympathetic (i.e. dorsal vagal complex and nucleus ambiguous) branches of the autonomic nervous system. These findings suggest that OXT increases central neural control of autonomic activity, rather than strictly dampening HPA axis activity, and provides a potential mechanism through which OXT may facilitate adaptive and context-dependent behavioral and physiological responses to stressors. PMID- 26836775 TI - Host immunity and pathogen diversity: A computational study. AB - The distinctive features of human influenza A phylogeny have inspired many mathematical and computational studies of viral infections spreading in a host population, but our understanding of the mechanisms that shape the coupled evolution of host immunity, disease incidence and viral antigenic properties is far from complete. In this paper we explore the epidemiology and the phylogeny of a rapidly mutating pathogen in a host population with a weak immune response, that allows re-infection by the same strain and provides little cross-immunity. We find that mutation generates explosive diversity and that, as diversity grows, the system is driven to a very high prevalence level. This is in stark contrast with the behavior of similar models where mutation gives rise to a large epidemic followed by disease extinction, under the assumption that infection with a strain provides lifelong immunity. For low mutation rates, the behavior of the system shows the main qualitative features of influenza evolution. Our results highlight the importance of heterogeneity in the human immune response for understanding influenza A phenomenology. They are meant as a first step toward computationally affordable, individual based models including more complex host-pathogen interactions. PMID- 26836777 TI - Thiophene-S,S-dioxidized Indophenine: A Quinoid-Type Building Block with High Electron Affinity for Constructing n-Type Polymer Semiconductors with Narrow Band Gaps. AB - Three thiophene-S,S-dioxidized indophenine (IDTO) isomers, 3 a (E,E,E), 3 b (Z,E,E), and 3 c (Z,E,Z), were synthesized by oxidation of an indophenine compound. 3 b and 3 c could be converted into the most-stable 3 a by heating at 110 degrees C. An IDTO-containing conjugated polymer, PIDTOTT, was prepared using 3 a as a comonomer through a Stille coupling reaction, and it possesses a narrow band gap and low energy levels. In organic field effect transistors (OFETs), PIDTOTT exhibited unipolar n-type semiconductor characteristics with unexpectedly high electron mobility (up to 0.14 cm(2) V(-1) s(-1)), despite its rather disordered chain packing. PMID- 26836776 TI - Correlation between Maternal Characteristics during Early Pregnancy, Fetal Growth Rate and Newborn Weight in Healthy Pregnancies. AB - BACKGROUND: The objective of this study was to evaluate the association between maternal characteristics in early pregnancy and fetal growth (FG) and birth weight (BW). METHODS: A prospective cohort study was performed in unselected pregnant women who attended an ultrasound evaluation at 11-14 weeks of pregnancy. Medical history, biochemical blood tests, biophysical variables and fetal weight at 20-25 and 30-36 weeks as well as the BW were assessed. Bivariate and multivariate linear models were constructed. RESULTS: In all, 543 patients with normal pregnancy and labor were selected. The multiple regression analysis showed a statistically significant association between maternal body mass index (BMI) in early pregnancy and the uterine artery pulsatility index (UtAPI) in the first trimester with BW (p < 0.0008) and with the ratio of fetal growth between the second and third trimesters (p < 0.0001). No correlation was found between these variables and first trimester levels of hemoglobin or glycemia. CONCLUSION: Maternal first trimester BMI and UtAPI correlate with the rate of intrauterine FG and with the BW. This evidence highlights the influence of maternal first trimester variables on fetuses with normal growth and the potential role of these variables in fetal programming. PMID- 26836778 TI - Molecular modeling study on the drug resistance mechanism of NS5B polymerase to TMC647055. AB - NS5B polymerase plays an important role in viral replication machinery. TMC647055 (TMC) is a novel and potent non-nucleoside inhibitor of the HCV NS5B polymerase. However, mutations that result in drug resistance to TMC have been reported. In this study, we used molecular dynamics (MD) simulations, binding free energy calculations, and free energy decomposition to investigate the drug resistance mechanism of HCV to TMC resulting from L392I, P495T, P495S, and P495L mutations in NS5B polymerase. From the calculated results we determined that the decrease in the binding affinity between TMC and NS5B(L392I) polymerase is mainly caused by the extra methyl group at the CB atom of Ile. The polarity of the side-chain of residue 495 has no distinct influence on residue 495 binding with TMC, whereas the smaller size of the side-chain of residue 495 causes a substantial decrease in the van der Walls interaction between TMC and residue 495. Moreover, the longer length of the side-chain of residue 495 has a significant effect on the electrostatic interaction between TMC and Arg-503. Finally, we performed the same calculations and detailed analysis on other 3 mutations (L392V, P495V, and P495I). The results further confirmed our conclusions. The computational results not only reveal the drug resistance mechanism between TMC647055 and NS5B polymerase, but also provide valuable information for the rational design of more potent non-nucleoside inhibitors targeting HCV NS5B polymerase. PMID- 26836779 TI - A wireless accelerometer node for reliable and valid measurement of lumbar accelerations during treadmill running. AB - This study investigated the reliability of a wireless accelerometer and its agreement with optical motion capture for the measurement of root mean square (RMS) acceleration during running. RMS acceleration provides a whole-body metric of movement mechanics and economy. Fifteen healthy college-age participants performed treadmill running for two 60-s trials at 2.22, 2.78, and 3.33 m/s and one trial of 150 s (five 30-s epochs) at 2.78 m/s. We assessed between-trial and within-trial reliability, and agreement in each axis between a trunk-mounted wireless accelerometer and a reflective marker on the accelerometer measured by optical motion capture. Intraclass correlations assessing between-trial repeatability were 0.89-0.97, depending on the axis, and intraclass correlations assessing within-trial repeatability were 0.99-1.00. Bland-Altman analyses assessing agreement indicated mean difference values between -0.03 and 0.03 g, depending on the axis. Anterio-posterior acceleration had the greatest limits of agreement (LOA) (+/-0.12 g) and vertical acceleration had the smallest LOA (+/ 0.03 g). For measuring RMS acceleration of the trunk, this wireless accelerometer node provides repeatable and valid measurement compared with the standard laboratory method of optical motion capture. PMID- 26836780 TI - The Rise of Consumer Health Wearables: Promises and Barriers. PMID- 26836781 TI - Comparison of adjunctive azithromycin and amoxicillin/metronidazole for patients with chronic periodontitis: preliminary randomized control trial. AB - BACKGROUND: There are insufficient guidelines for the use of adjunctive systemic antibiotics for patients with periodontal disease. The aim of this study was to compare clinical outcomes for patients with moderate-advanced chronic periodontitis treated with: scaling and root planing (SRP), SRP with amoxicillin and metronidazole (A+M), SRP with Azithromycin (Az). METHODS: Thirty-seven non smokers with generalized moderate to advanced chronic periodontitis were divided into three treatment groups: SRP, A+M and Az. Patients received the medications after the last SRP session and were reviewed three months later. Changes in clinical parameters were compared between the groups. Separate analyses were executed for: 'all sites', 'molar sites', 'sites with different PPD severities' and 'number of sites with shallow, moderate and deep PPD'. RESULTS: The three groups exhibited improvements in most clinical parameters. At three months, A+M showed a higher reduction in PPD compared to Az in the 'all sites analysis'. Molars exhibited better reduction in BOP and PPD with A+M than SRP. Pocket depth of the 4-6 mm category reduced more in the A+M than SRP. A+M experienced a higher increase in the number of sites with PPD 1-3 mm than Az. CONCLUSIONS: Adjunctive systemic antibiotics in the initial phase of treatment may result in improved clinical outcomes. PMID- 26836782 TI - Platelet concentrates for revitalization of immature necrotic teeth: a systematic review of the clinical studies. AB - This systematic review aimed at determining the effectiveness of autologous platelet concentrate (APC) in the treatment of immature necrotic teeth. An electronic search was performed on MEDLINE, Embase, Scopus, SciELO, Lilacs, CENTRAL. Comparative clinical studies were included, in which APC was tested for pulp regeneration and radicular development. Selected articles underwent risk-of bias assessment. Clinical and radiographic outcomes were considered. Three randomized parallel studies and one split-mouth case series were included. One study had low risk of bias and three studies had high risk. A total of 61 immature necrotic teeth were treated in 56 patients. Follow-up ranged between 12 and 18 months. All studies used platelet-rich plasma (PRP) in the test group, and one also used platelet-rich fibrin (PRF). After treatment, all teeth of control and experimental groups remained asymptomatic for the entire study duration. Only one study reported response to cold and electric pulp test, showing not significantly better outcomes for the test group. Similarly, periapical healing and apical closure were improved in the group treated with APC although statistical significance was not achieved (P = 0.08 and P = 0.06, respectively), probably due to the limited sample size. The teeth treated with PRP achieved significantly better thickening of the dentin walls (P = 0.01), and root lengthening (P = 0.001) than control teeth. Despite the potential effectiveness of APC in promoting root development of necrotic immature teeth, scarce evidence exists regarding this subject. In the studies evaluated in this review, platelet concentrates showed promising results that warrant further investigation. PMID- 26836783 TI - Patient physiological status during emergency care and rapid response team or cardiac arrest team activation during early hospital admission. AB - OBJECTIVES: The objective of this study was to examine the relationship between rapid response team (RRT) or cardiac arrest team (CAT) activation within 72 h of emergency admission and (i) physiological status in the emergency department (ED) and (ii) risk for ICU admission and in-hospital mortality. METHODS: A retrospective matched cohort study was conducted in three hospitals in Melbourne, Australia. The exposed cohort (n=660) included randomly selected adults admitted to the medical or surgical ward through the ED who had RRT or CAT activation within 72 h of admission. Unexposed matched controls (n=1320) did not have RRT or CAT activation. RESULTS: The exposed cohort was more likely to have physiological abnormalities fulfilling hospital RRT activation criteria during ED care (36.7 vs. 23.8%, P<0.001). After adjusting for confounders, tachypnoea (adjusted odds ratio=1.92, 95% confidence interval: 1.38-2.67) or hypotension (AOR=1.43, 95% confidence interval: 1.00-2.03), fulfilling RRT activation criteria during ED care, was associated with RRT or CAT activation within 72 h of admission. The exposed cohort had more in-hospital deaths (16.5 vs. 3.6%, P<0.001), more unexpected in-hospital deaths (2.05 vs. 0.2%, P<0.001), more ICU admissions (11.8 vs. 0.7%, P<0.001) and longer lengths of hospital stay (median=8 vs. 5 days, P<0.001). CONCLUSION: CAT/RRT activations within 72 h of emergency admission are associated with higher mortality and increased length of stay. Factors associated with CAT/RRT activation in the wards are often identifiable when patients are in the ED. Further studies are required to determine whether early identification and intervention in patients at risk for RRT or CAT activation can improve their eventual outcomes. PMID- 26836784 TI - Development of an in vivo swine model of biliary dilatation-based direct peroral cholangioscopy. AB - BACKGROUND AND AIM: A reproducible in vivo swine model of bile duct dilation (BDD) was recently established and reported for preclinical testing of newly developed biliary devices or endoscopic techniques. The aim of the present study was to develop a more advanced large animal model in which it is possible to direct examination of the biliary tree. Methods Six mini pigs were prepared for the study. BDD models were first made by closure of the Vater's ampulla in all swine. Then endoscopic papillary balloon dilation (EPBD) was done in the animals. Feasibility of single-operator peroral cholangioscopy without assistance of accessories was evaluated using an ultra-slim upper endoscope in the animals. Results EPBD could be implemented using a dilation balloon catheter (10~13.5 mm) in all BDD models (6/6, 100%). Success rate of freehand direct insertion of an ultra-slim endoscope into the common bile duct was 100% (6/6), and access to the common hepatic duct with examination was possible using direct peroral cholangioscopy in five animals (5/6, 83.3%). None of the animals died. In the cholangioscopic examination, a bile duct polyp and a benign biliary stricture occurred naturally, respectively, in two of the six swine. Conclusion An in vivo swine model of biliary dilatation-based direct peroral cholangioscopy was established. This novel animal model may be useful for preclinical research of new materials or devices because direct visualization of the biliary tree is feasible. PMID- 26836785 TI - Directly acting antivirals for hepatitis C virus arrive in HIV/hepatitis C virus co-infected patients: from 'mind the gap' to 'where's the gap?'. AB - In patients living with HIV infection with hepatitis C (HCV) is common. HIV/HCV co-infection results in more rapid liver fibrosis progression than HCV alone and end-stage liver disease is a major cause of morbidity and mortality in co infected patients. Historically, treatment outcomes with interferon based therapy in this group have been poor but with the advent of directly acting antiviral (DAA) drugs for HCV, rates of cure have improved dramatically. This article reviews recent evidence on the treatment of HCV in co-infected patients including the efficacy of new regimens and information on drug-drug interactions between DAAs and antiretroviral therapy. We also discuss the relationship between the pathogenesis of HIV and HCV infections, the treatment of acute hepatitis C and the current debate regarding the cost-effectiveness and affordability of DAAs. PMID- 26836786 TI - Incidence of stage 3 chronic kidney disease and progression on tenofovir-based regimens. AB - OBJECTIVE: To describe the incidence of rapid kidney function decline (RKFD), and stage 3 chronic kidney disease (CKD) in HIV-1-infected adults initiated on tenofovir-containing antiretroviral therapy. METHODS: A retrospective cohort study at the infectious diseases clinic of Tygerberg Academic Hospital in Cape Town, South Africa. Patients with more than 3 ml/min per year decline in estimated glomerular filtration were classified as having RKFD, and stage 3 CKD was defined as a value less than 60 ml/min per 1.73 m. We used logistic and Cox proportional hazards regression models to determine factors associated with RKFD and stage 3 CKD. RESULTS: Of 650 patients, 361 (55%) experienced RKFD and 15 (2%) developed stage 3 CKD during a median interquartile range follow-up time of 54 (46.6-98) weeks. For every 10-year increase in age and 10 ml/min lower baseline estimated glomerular filtration, the odds of RKFD increased by 70% [adjusted odds ratio = 1.70, 95% confidence interval (CI) 1.36-2.13] and 57% (adjusted odds ratio = 1.57, 95% CI 1.38-1.80), respectively. Each 10-year older age was associated with a 1.90-fold increased risk of developing stage 3 CKD (adjusted hazard ratio = 1.90, 95% CI: 1.10-3.29). Women had about four-fold greater risk of stage 3 CKD compared with men (adjusted hazard ratio = 3.96, 95% CI: 1.06 14.74). CONCLUSION: About half of our study population developed RKFD but only 2% progressed to stage 3 CKD. Approaches that provide balanced allocation of limited resources toward screening and monitoring for kidney dysfunction and HIV disease management are critically needed in this setting. PMID- 26836787 TI - HIV infection among persons who inject drugs: ending old epidemics and addressing new outbreaks. AB - AIDS among persons who inject drugs, first identified in December 1981, has become a global epidemic. Injecting drug use has been reported in 148 countries and HIV infection has been seen among persons who inject drugs in 61 countries. Many locations have experienced outbreaks of HIV infection among persons who inject drugs, under specific conditions that promote very rapid spread of the virus. In response to these HIV outbreaks, specific interventions for persons who inject drugs include needle/syringe exchange programs, medicated-assisted treatment (with methadone or buprenorphine) and antiretroviral therapy. Through a 'combined prevention' approach, these interventions significantly reduced new HIV infections among persons who inject drugs in several locations including New York City, Vancouver and France. The efforts effectively ended the HIV epidemic among persons who inject drugs in those locations. This review examines possible processes through which combined prevention programs may lead to ending HIV epidemics. However, notable outbreaks of HIV among persons who inject drugs have recently occurred in several countries, including in Athens, Greece; Tel-Aviv, Israel; Dublin, Ireland; as well as in Scott County, Indiana, USA. This review also considers different factors that may have led to these outbreaks. We conclude with addressing the remaining challenges for reducing HIV infection among persons who inject drugs. PMID- 26836788 TI - A prospective study of anal cancer screening in HIV-positive and negative MSM. AB - OBJECTIVE: The study sought to establish the feasibility and acceptability of anal screening among men MSM. DESIGN: Prospective cohort study. SETTING: Sexual health clinics in tertiary care. PATIENTS: Known HIV-positive and negative MSM who have anoreceptive intercourse. INTERVENTION: Anal screening with human papilloma virus (HPV) testing, liquid-based cytology and high-resolution anoscopy with biopsy of anoscopic abnormalities. Participants completed questionnaires at baseline and at 6 months. RESULTS: Anal HPV was highly prevalent in MSM (HIV positive, 88% and HIV-negative, 78%). Despite the high prevalence of cytological abnormality in both HIV-positive (46.2%) and negative (35.0%) MSM, almost half of anal intraepithelial neoplasia (AIN) of all grades were associated with negative cytology. Anoscopically directed biopsies detected AIN3 or worse (AIN3+) in 14 of 203 (6.9%) of HIV-positive MSM and three of 81 (3.7%) HIV-negative MSM. The corresponding prevalence of AIN2+ was 26.6 and 20.9%, respectively. One case of AIN3 was detected at the second visit. Screening was considered to be highly acceptable by participants. CONCLUSION: The high prevalence of high-risk-HPV and frequency of false negative cytology in this study suggest that high-resolution anoscopy would have most clinical utility, as a primary screening tool for anal cancer in a high-risk group. The prevalence of AIN3+ in HIV-positive MSM lends support for a policy of screening this group, but the high prevalence of lower grade lesions which do not warrant immediate treatment and the limitations of treating high-grade lesions requires careful consideration in terms of a screening policy. PMID- 26836789 TI - The pharmacokinetics of abacavir 600 mg once daily in HIV-1-positive pregnant women. AB - OBJECTIVE: To describe the pharmacokinetics of abacavir 600 mg once daily (q.d.) in HIV-1-positive women during pregnancy and postpartum. DESIGN: A nonrandomized, open-label, multicentre, phase-IV study. METHODS: HIV-positive pregnant women receiving abacavir 600 mg q.d. as part of clinical care were included. Intensive 24-h pharmacokinetic sampling was performed during the third trimester and at least 2 weeks after delivery. Pharmacokinetic parameters were calculated by noncompartmental analysis. Paired cord blood and maternal blood samples were taken at delivery when feasible. RESULTS: A total of 14 women were included in the analysis. Geometric mean ratios (90% confidence intervals) of third trimester versus postpartum were 1.05 (0.92-1.19) for AUC0-24h and 1.00 (0.83-1.21) for Cmax. The median (range) ratio of abacavir cord plasma to maternal plasma was 1.0 (0.7-1.0, n = 3). Viral load at the third trimester visit was less than 50 copies/ml in 13 participants (93%; one unknown). In total, 13 (93%; one unknown) children were tested HIV-negative. CONCLUSION: The pharmacokinetics of abacavir 600 mg q.d. during pregnancy are equivalent to postpartum. No dose adjustments are required during pregnancy and similar antiviral activity is expected. PMID- 26836791 TI - Sharing clinical trial data: a proposal from the International Committee of Medical Journal Editors. PMID- 26836792 TI - Contacts to general practice and antidepressant treatment initiation after screening for anxiety and depression in patients with heart disease. AB - INTRODUCTION: Anxiety and depression are found in 20-30% of all persons with heart disease, and depression is known to impact mortality. This paper aimed to describe the effect of systematic screening of this population in terms of use of general practice, psychological therapy and antidepressant treatment. METHODS: A population-based cohort study was conducted in 2011-2013 comprising 1,658 people with heart disease treated at a Danish regional hospital. Collected data were based on Danish national registers and patient questionnaires. RESULTS: Patients with heart disease and anxiety or depressive symptoms had more general practitioner (GP) contact rates than patients without anxiety or depressive symptoms both before and after the screening. Furthermore, patients with depressive symptoms increased their GP contact rate significantly in the first month after the screening, while this was not the case for patients with anxiety symptoms. Finally, patients with heart disease and anxiety or depressive symptoms more frequently initiated treatment with antidepressants than patients with heart disease without anxiety or depressive symptoms, whereas therapy sessions with a psychologist were rarely used. CONCLUSIONS: Heart patients with depressive symptoms may benefit from screening for depression, information about the screening result and a subsequent recommendation to consult their GP in case of signs of depression. -However, the observed effect seems to be modest. FUNDING: The study was supported by an unrestricted grant from the Lundbeck Foundation (grant number: R155-2012-11280). TRIAL REGISTRATION: none. PMID- 26836790 TI - Broadly neutralizing antibody specificities detected in the genital tract of HIV 1 infected women. AB - BACKGROUND: Broadly neutralizing antibodies (bNAbs) targeting conserved epitopes on the HIV envelope glycoprotein have been identified in blood from HIV-1 infected women. We investigated whether antibodies in the genital tract from these women share similar epitope specificities and functional profiles as those in blood. METHODS: Immunoglobulin (Ig)G and IgA antibodies were isolated from cervicovaginal lavages or Softcups from 13 HIV-infected women in the CAPRISA cohort using Protein G and Peptide M, respectively. Binding antibodies to envelope antigens were quantified by ELISA and binding antibody multiplex assay. Neutralizing antibody titers and epitope targets were measured using the TZM-bl assay with Env-pseudotyped wild-type and mutated viruses. RESULTS: HIV-specific IgG, but not IgA, was detected in genital secretions and the ratio of total IgG to HIV-specific IgG was similar to plasma. HIV-specific IgG reacted with multiple envelope antigens, including V1V2, gp120, gp140 and gp41. Two women had high plasma titers of HIV-specific IgG3 which was also detected in their genital tract samples. IgG from the genital tract had neutralizing activity against both Tier 1 and Tier 2 primary HIV-isolates. Antibodies targeting well known glycan epitopes and the membrane proximal region of gp41 were detected in genital secretions, and matched specificities in plasma. CONCLUSIONS: Women with plasma bNAbs have overlapping specificities in their genital secretions, indicating that these predominantly IgG isotype antibodies may transudate from blood to the genital tract. These data provide evidence that induction of systemic HIV-specific bNAbs can lead to antiviral immunity at the portal of entry. PMID- 26836794 TI - Questionnaire-based survey suggests that the majority of Danish geriatricians are against euthanasia. AB - INTRODUCTION: Euthanasia (EU) and/or physician-assisted suicide (PAS) is legal in some countries and being considered in others. Attitudes to EU/PAS among Danish geriatricians were studied. METHODS: An online questionnaire with 12 questions was e-mailed to all members of the Danish Geriatric Society. RESULTS: The response rate was 46% (120/261). A total of 55.8% (67/120) disagreed that EU is ethically justifiable, whereas 22.5% (27/120) found that EU is justifiable. Furthermore, 13.3% (16/120) agreed that EU should be offered as an alternative to palliative treatment, 73.4% (88/120) disagreed. A total of 64.2% (67/120) disagreed that PAS is ethically justifiable, whereas 19.2% (23/120) found that PAS is justifiable. In all, 15% (18/120) agreed that PAS should be offered as an alternative to palliative treatment, whereas 76.6% (92/120) disagreed. The impact of legalisation of EU/PAS on the relationship between physician and patient was believed to be negative by 62.2% (74/119), positive by 12.6% (15/119) and without implications by 25.2% (30/119). Younger physicians tended to be more positive towards EU/PAS. CONCLUSIONS: The majority of Danish geriatricians are opposed to EU and PAS. FUNDING: none. TRIAL REGISTRATION: none. PMID- 26836793 TI - Safety of novel oral anticoagulants in catheter ablation of atrial fibrillation. AB - INTRODUCTION: Limited data are available regarding safety of catheter ablation of atrial fibrillation (AF) in patients using novel oral anticoagulants (NOAC) before and after pulmonary vein isolation. We aimed to assess the safety of a simple anticoagulation protocol in consecutive patients presenting for catheter ablation of AF. METHODS: From November 2011 to December 2014, we prospectively included 234 patients referred for catheter ablation of AF who had already received NOAC treatment. NOAC was continued for a minimum of three months after ablation. We assessed procedure-related bleeding or thromboembolic complications, bleeding or thromboembolic complications during a three-month follow-up period and patient-reported adherence to NOAC therapy. The study has not received financial support from external resources. The study was registered with ClinTrials.gov as NCT02569255. RESULTS: A total of 171 patients were treated with dabigatran (94% 150 mg twice daily), 38 with rivaroxaban (100% 20 mg daily) and 25 with apixaban (100% 5 mg twice daily). NOACs were interrupted for 24 hours before and re-administered two hours after the ablation procedure, without bridging with low molecular weight heparin (LMWH). No periprocedural thromboembolic complications and no bleeding complications were registered except for one pericardial effusion which was percutaneously drained without further complications. No thromboembolic or bleeding complications during follow-up were registered. All patients continued the same NOAC during follow-up as before ablation. CONCLUSIONS: Anticoagulation with NOAC with a short period of periprocedural interruption without bridging with LMWH seems safe and well tolerated. FUNDING: none. TRIAL REGISTRATION: The trial is registered as ClinTrials.gov no. NCT01569255. PMID- 26836795 TI - The use of ultrasound to identify veins for peripheral venous access in morbidly obese patients. AB - INTRODUCTION: Peripheral intravenous access (PIA) is a necessity in the treatment and monitoring of the majority of hospitalised patients. Patients with an increased body mass index (BMI) more often than normal-weight patients have a difficult PIA. Identifying veins with ultrasonography has proven helpful when facing a difficult intravenous (IV) access. We hypothesise that, with the help of ultrasonography (US), it is possible to identify at least one vein suitable for IV access in morbidly obese patients (BMI > 40 kg/m(2)). METHODS: We included 55 morbidly obese patients with a BMI > 40 kg/m(2). We performed a detailed US of seven anatomic areas routinely used for PIA. We present a description of parameters that are relevant when attempting PIA. RESULTS: In our study group, all patients had a minimum of one peripheral vein that was suitable for peripheral venous access, including seven patients (12.7%) who did not have clinically detectable veins. CONCLUSIONS: With the aid of US it is possible to identify a minimum of one peripheral vein suitable for IV access in morbidly obese patients. FUNDING: none. TRIAL REGISTRATION: not relevant. PMID- 26836796 TI - En bloc ligation of renal vessels is safe and reduces duration of surgery. AB - INTRODUCTION: Conventionally, individual ligation of the renal vessels with clips is performed during laparoscopic nephrectomy (LN). Concomitant ligation of the vessels is not a standard procedure due to an expected risk of stapler dysfunction and the development of arteriovenous fistulas (AVF). Using the EndoGIA stapler 45/2.5 mm, we compared en bloc ligation with individual ligation during LN and nephroureterectomy (LNU) with a special focus on the development of AVF and technique safety. METHODS: This was a retrospective study of all patients undergoing LN or LNU at the Department of Urology, Roskilde Hospital, Denmark, between January 2010 and April 2014. The follow-up period was minimum six months. RESULTS: A total of 228 patients underwent LN and 56 patients underwent LNU. In the LN group, 77 patients underwent en bloc ligation. The mean surgical time was significantly reduced to 89 minutes in the en bloc group compared to 109 minutes in the conventional group (p = 0.0001). The difference remained significant with multivariate analysis. In the LNU group, seven patients underwent en bloc ligation. There was no significant difference between conventional ligation and en bloc ligation with respect to surgical time in either the univariate or the multivariate analyses. None of the patients needed blood transfusion. With a mean follow-up of 13.5 months, no AVF were found. CONCLUSIONS: En bloc ligation appears to be safe and can reduce the surgical time during LN without increased risk of blood transfusion and without development of AVF. Further studies are needed to assess any advantages associated with use of the method during LNU. FUNDING: none. TRIAL REGISTRATION: not relevant. PMID- 26836797 TI - Radiographers are valuable contributors in interpreting computed tomography colonography. AB - INTRODUCTION: Computed tomography colonography (CTC) is the primary radiological examination for detection of colorectal cancer and premalignant polyps. It is a complex technique that requires special training and experience of both the radiographers performing the colonography and the radiologists who interpret the results. The considerable number of CTC performed means that interpretation of the examinations is a time-consuming task for radiologists. Therefore, this study aimed to evaluate the diagnostic performance of radiographers who received a training programme in colon diagnosing. METHODS: During the period from December 2014 to May 2015, 126 patients underwent CTC screening or diagnostics. The colon was interpreted by both a radiographer and an experienced radiologist. Subsequently, results were compared and consensus established. RESULTS: A total of 100 patients were included, six polyps (6-9 mm), one polyp (>= 10 mm), four cancer suspect areas and four second opinions. The result was nine true positives, three false positives, no false negatives and 84 true negatives corresponding to a negative predictive value of 1.000 and an accuracy of 0.969. CONCLUSIONS: This study shows that radiographers can be a valuable contribution in the interpretation of CTC. FUNDING: This study was funded by Marie Pedersen and Jensine Heiberg's legat, Vendsyssel Hospital, Denmark. TRIAL REGISTRATION: not relevant. PMID- 26836798 TI - Simplified screening in an emergency department detected methicillin-resistant Staphylococcus aureus. AB - INTRODUCTION: All patients admitted to Danish hospitals are screened for methicillin-resistant Staphylococcus aureus (MRSA) by a questionnaire consisting of 19 questions issued by the Danish Health and Medicines Authority (DHMA). This study aimed to evaluate which of the questions were most useful. Furthermore, we assessed if other questions were more adequate and if a simplified screening model would perform equal to or better than the one presently used. METHODS: Swabs were obtained for MRSA culture from patients who were more than ten years old and who had been admitted to an emergency department (ED). All DHMA questions together with a range of additional questions were answered. RESULTS: Among the 1,220 patients who participated, 0.9% were MRSA carriers. Only three DHMA questions were associated with a significant risk of MRSA carriage. The additional questions associated with MRSA were "stayed with a non-Danish family within the past three years" and "daily contact with children at a nursery or kindergarten". A new model with only five questions increased the sensitivity insignificantly from 18-55% to 73% in the revised model, whereas no changes were seen for specificity, predictive values or likelihood ratios. CONCLUSIONS: The DHMA's targeted screening for MRSA detection contained only few questions with significant association to MRSA carrier stage. A model based on only five questions seems to insignificantly improve the MRSA screening in this population. In order to develop a more simple and effective screening model, we recommend that our findings be tested in another ED patient population. FUNDING: Southern Jutland Hospital funded this study. TRIAL REGISTRATION: not relevant. PMID- 26836799 TI - Therapeutic hypothermia after cardiac arrest in a real-life setting. AB - INTRODUCTION: In 2002, two landmark studies concluded that therapeutic hypothermia (TH) improves survival and neurologic outcome in patients with shockable rhythms and out-of-hospital cardiac arrest (OHCA). However, the evidence on whether TH also improves the prognosis in patients with non-shockable rhythms or in-hospital cardiac arrest (IHCA) is sparse. The aim of this study was to assess the prevalence and prognosis of patients with non-shockable rhythms or IHCA after implementation of TH in a real-life setting. METHODS: The study included 72 consecutive, unconscious patients that were admitted to Holbaek Hospital after cardiac arrest and successful resuscitation. Patients were included regardless of initial cardiac rhythms and location of the cardiac arrest. All patients were cooled to a temperature of 32-34 degrees C. The primary outcome was survival with a favourable neurologic outcome within six months. RESULTS: Almost two thirds (63%) of the included patients had non shockable rhythms or IHCA and only 8.7% of these patients survived with a favourable neurologic outcome. Nearly a third (29%) of the included patients had OHCA with an initial non-shockable rhythm and none (0%) of these patients survived with a favourable neurologic outcome. CONCLUSIONS: In a real-life setting, the majority of resuscitated patients receiving TH do not fulfil the criteria of the original studies upon which the current guidelines are based. Furthermore, these patients have a poor outcome, indicating that not all patients may benefit from TH. FUNDING: none. TRIAL REGISTRATION: not relevant. PMID- 26836800 TI - The pathological phenotype of colon cancer with microsatellite instability. AB - INTRODUCTION: Colorectal cancer is a common malignant disease, caused by different aetiologies and molecular pathways. Heterogeneous results have been published regarding the association of microsatellite instability and clinicopathological features. The aim of this study was to compare clinicopathological features of microsatellite unstable tumours with stable ones. METHODS: Data were collected retrospectively, but the pathological analyses were all made prospectively. The study included a total of 833 patients undergoing resection of their colon tumour at Nordsjaellands Hospital - Hillerod, with mismatch repair analysis from 1 January 2007 to 30 November 2012. The study was performed in a setting with complete mesocolic excision surgery and post operative expert pathological examination of the tumours. Mismatch repair analysis was done by immuno-histochemical staining for the mismatch repair proteins: pMLH1, pMSH2, pMSH6 and pPMS2 for the determination of microsatellite instability. Microsatellite instability was defined as deficient expression of one or more of these proteins. RESULTS: Of the 833 patients, 177 had microsatellite instable tumours (21%). Using multivariable logistic regression analysis, we demonstrated that microsatellite unstable cancers were significantly associated with a lower degree of lymph node metastases (odds ratio (OR) = 0.92), distant metastases (OR = 0.33) and tumour budding (OR = 0.41). CONCLUSIONS: We found that microsatellite unstable tumours show a pathological profile that appears less aggressive than the pathological profile of stable tumours. FUNDING: none. TRIAL REGISTRATION: not relevant. PMID- 26836802 TI - Modulation of motoneuron activity by serotonin. AB - Serotonin is a major neuromodulator in the central nervous system involved in most physiological functions including appetite regulation, sexual arousal, sleep regulation and motor control. The activity of neurons from the raphe spinal tract, which release serotonin on motoneurons, is positively correlated with motor behaviour. During moderate physical activity, serotonin is released from synaptic terminals onto the dendrites and cell bodies of motoneurons. Serotonin increases the excitability of motoneurons and thereby facilitate muscle contraction by acting on several parallel intracellular pathways. By activating 5 HT1A receptors, serotonin inhibits TWIK-related acid-sensitive potassium channels and small conductance calcium-activated potassium channels. In parallel, serotonin binds to 5-HT2 receptors, which promotes the low-threshold L-type Ca(2+) channels. During intense physical activity, more serotonin is released. The reuptake systems saturate and serotonin spills over to reach extrasynaptic 5 HT1A receptors located on the axon initial segment of motoneurons. This in turn induces the inhibition of the Na(+) channels responsible for the initiation of action potentials. Fewer nerve impulses are generated and muscle contraction becomes weaker. By decreasing the gain of motoneurons, serotonin triggers central fatigue. PMID- 26836801 TI - Moxibustion did not have an effect in a randomised clinical trial for version of breech position. AB - INTRODUCTION: In Chinese traditional medicine, the stimulation of acupuncture point no. 67 - the bladder meridian - is recommended to favour cephalic version in case of foetal breech presentation. The point can be stimulated by an acupuncture needle, ginger application, fingertip pressure, laser or moxibustion; moxibustion is heat generated by a burning stick containing the herb Artemisia vulgaris. A Cochrane review concluded that more research on the effectiveness of moxibustion is needed. This study aimed to estimate the effectiveness of moxibustion for version of breech presentation. METHODS: We included 200 women in gestational week 33 who had a singleton foetus in breech position. They were randomised to moxibustion treatment daily for two weeks or control without moxibustion. The randomisation was performed for nulliparous and parous women separately. RESULTS: After the trial, which lasted on average 16 days, the breech position was confirmed in 68 of the 92 nulliparous and in 50 of the 108 parous women (74% versus 46%, p < 0.01); furthermore, cephalic position was verified in 76 women and other positions in six women. No significant difference regarding the incidence of breech position was found in the moxibustion group compared with the control group (risk ratio (RR) = 1.05, 95% confidence interval (CI): 0.8 1.38); nor in nulliparous (RR = 1.17, 95% CI: 0.77-1.76) or in parous women (RR = 1.0, 95% CI: 0.69-1.46); an RR > 1 favours moxibustion). CONCLUSIONS: No significant effects of moxibustion were found in correcting the breech position in primiparous and parous women after their 33rd gestational week. FUNDING: none. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov as NCT02251886. PMID- 26836803 TI - The road to success. Long-term prognosis for persons living with HIV in Denmark - time trends and risk factors. AB - The work on this thesis began in 2003 when the global HIV epidemic was out of control. A minority of persons with HIV were benefitting fully from the recently introduced highly efficacious antiretroviral therapy (ART) combinations. Among the global challenges were lack of access to good healthcare, drug toxicity, and emergence of drug-resistant virus. It was unknown how long the drugs could maintain their efficacy in the individual even if administered as intended, and there was a fear that the increased drug pressure would increase the prevalence of drug resistance, subsequently leading to transmission of resistant virus from one individual to another, and thereby waning the treatment options available. Hence, we were far from the ideal conditions where an HIV-infected individual gets to know immediately that he/she is infected, has access to specialized medical and social support, receives a drug combination which effectively suppresses the virus and has no side effects, and is free of co-morbid conditions both before and after he/she gets infected. The nine papers on which this thesis is based each aimed to provide new knowledge to aspects of the above. Late diagnosis and late presentation to clinical care continue to be major barriers to improved HIV management. We used nation-wide hospital registries to explore the potential for an indicator disease-based HIV testing strategy. A range of conditions that were manifestations of the HIV infection itself were found to be associated with highly increased risk of HIV diagnosis during the coming year, but less so three to five years later. Other conditions were associated with an almost constant five-year long increased risk of being diagnosed with HIV because they share behavioural risk factors with HIV, making them indicators of not only current HIV but also of future HIV acquisition. Hence, indicator condition-based testing should be adapted to the local epidemic and could be a valuable addition to the existing detection practice. Once diagnosed, getting the full benefit of modern HIV care requires access to a good healthcare system. We compared temporal trends in quality and quantity of ART introduction in Den-mark and Greenland. Despite similar levels of health worker education and economic resources, ART implementation and mortality decline in Greenland lacked several years behind Denmark. The study reminded us that although economy may be a prerequisite for implementing an effective HIV care system, it is certainly not all it takes. The nationwide nature of the Danish HIV Cohort Study also allowed us to study a number of time trends at the population level. Despite what was feared, we found that the prevalence of triple-drug class virological failure (TCF) seemed to have stabilized after 2000; that the incidence rates of drug resistance acquisition were decreasing during 1999-2005; and that the prevalence of potential transmitters of drug-resistant HIV decreased during 1997-2004. We also looked at some of the consequences of virological failure and drug resistance and found that even modest levels of viraemia were associated with a high risk of future failure and death, and that in persons who have experienced TCF, the number and pattern of resistance mutations were independent predictors of death. Hence, despite the overall positive trends in virological failure and drug-resistance development at the population level, our findings underline the crucial importance of always having an effective treatment option available for the individual patient with drug-resistant virus. As mortality was declining for persons with access to ART and good HIV care, it became important to know how long persons with HIV could expect to live compared to the general population. We projected long-term survival and found that a 25-year old person with HIV and without hepatitis C virus (HCV) co-infection had a 50 per cent chance of surviving another 39 years, only 12.2 years less than a person in a matched general population cohort would survive. With improved survival and declining HIV related co-morbidity, non-HIV related co-morbidity became a more visible contributor to the health status of persons with HIV. We assessed the impact of non-HIV related comorbidity acquired before the person became infected with HIV. We found that 32% of the observed mortality in our cohort was due to HCV and co morbidities measured by the Charlson Comorbidity Index, 13% corresponded to the background mortality in the population, and that only 55% of the mortality could be attributed to HIV. Our findings confirmed that persons acquiring HIV differ at large from the general population, and that we should not expect overall mortality rates in populations with HIV to reach the levels in the general population. This thesis attempted to map some of the many challenges on the road towards increased survival of individuals and populations with HIV up to a level, which today in many settings is close to that of the general population. The studies in this thesis have each paid their modest contribution to show how crucially important it is to be diagnosed in time, to have access to a well functioning health system, and to keep free of co-morbidity both before and after acquiring HIV. After many years of struggle and despair, and thanks to enormous advances in prevention and treatment, we are now looking towards a promising future. PMID- 26836804 TI - Psoriasis and comorbidities. Epidemiological studies. AB - Psoriasis is a prevalent chronic inflammatory disease whose exact aetiology is not fully understood, but both genetic and environmental factors have been implicated in the onset and progression of the disease. At the skin level, psoriasis is characterized by localized or widespread thick raised silvery-white scaling and pruritic plaques and studies have shown that psoriasis negatively affects patients' quality of life, and depression occurs more often in patients with psoriasis. However, data have shown that psoriasis is a systemic disease which affects the joints, vasculature, and other tissues as well. Indeed, approximately one-third of patients with psoriasis develop psoriatic arthritis, and patients with severe psoriasis have a shortened life expectancy. Although our knowledge of the pathogenesis of psoriasis has advanced significantly in the past decade, as have the pharmacological treatment options which are now available, several important knowledge gaps remain. Many of the proinflammatory mediators involved in psoriasis have also been implicated in some central nervous system (CNS) diseases. However, studies on associations between psoriasis and CNS diseases are scarce. Based on nationwide registry data from the entire Danish population, the present thesis examined the associations between psoriasis and certain CNS diseases. The specific objectives of this work were to investigate the independent impact of depression on the risk of cardiovascular disease (CVD) in patients with psoriasis, the relationship between psoriasis and uveitis, and the risk of incident multiple sclerosis (MS) following the onset of psoriasis, respectively. The main results were a significantly increased risk of myocardial infarction, stroke, and CVD death in patients with psoriasis during stages of acute depression. Moreover, we found a bidirectional relationship between psoriasis and uveitis, where the occurrence of either disease significantly increased the risk of the other. Perhaps most notably, however, was that we found a psoriasis-severity dependent increased risk of MS. In conclusion, psoriasis was significantly associated with certain CNS diseases, and the risk of CVD was strongly associated with acute depression in these patients. These novel findings suggest an important link between psoriasis and CNS diseases, and high-light the necessity for a holistic approach to the diagnosis and treatment of patients with psoriasis. PMID- 26836805 TI - Regulatory B and T cell responses in patients with autoimmune thyroid disease and healthy controls. AB - Autoimmune diseases occur due to faulty self-tolerance. Graves' disease (GD) and Hashimoto's thyroiditis (HT) are classic examples of organ-specific autoimmune diseases. GD is an auto-antibody-mediated disease where autoantibodies are produced against the thyroid stimulating hormone receptor (TSHR). HT is primarily a T-cell mediated disease, and whether B cells play a pathogenic role in the pathogenesis is still unclear. Both GD and HT are characterized by infiltration of the thyroid gland by self-reactive T cells and B cells. In the first paper of this thesis, the role of regulatory B cells (Bregs) and regulatory T cells (Tregs) were investigated in the context of GD and HT. First, we studied the role of the thyroid self-antigen, thyroglobulin (TG) in healthy donors. The self antigen TG, but not the foreign recall antigen tetanus toxoid (TT), was able to induce interleukin 10 (IL-10) secretion by B cells and CD4+ T cells. These IL-10 producing B cells (B10 cells) from healthy donors were enriched with the CD5+ and CD24hi phenotype. In addition, TG was able to induce IL-6 production by B cells. In contrast, TT induced production of Th1-type pro-inflammatory cytokines including interferon-gamma (IFN-gamma) and IL-2. In the second paper, the frequency and phenotype of B10 was investigated in healthy donors and patients with GD or HT. The frequencies of B10 cells were similar in the three groups, irrespective of whether IL-10 was induced by a combination of phorbol 12 myristate 13-acetate (PMA) and ionomycin, by CpG oligodeoxynucletodies (ODN) 2006, or by TG. Several phenotypes have been associated with B10 cells such as CD5+, CD25+, TIM-1+, CD24hiCD38hi and CD27+CD43+. We found that larger proportions of B10 cells in patients with GD or HT were CD25+ and TIM-1+ than B10 cells in healthy donors. In healthy donors, B10 cells were CD24hiCD38-, whereas for HT patients these cells were primarily CD24intCD38int. For GD patients, we found lower proportions of B10 cells within the CD27+CD43- and CD27-CD43- fractions than for healthy donors. Our data show that GD and HT are not associated with decreased frequencies of B10 cells. Accordingly, B10 cells may not be confined to one phenotype or subset of B cells. In the third paper, we studied the balance between IL-17-producing CD4+ T cells (Th17 cells) and IL-10 producing CD4+ T cells (Th10 cells) in healthy donors and patients with GD or HT. In HT patients, we found increased proportions of naive Th17 cells after stimulation with the thyroid self-antigen thyroid peroxidase (TPO) and the Escherichia coli lipopolysaccharide (E. coli LPS). The proportions of Th10 cells were similar in healthy donors and in HT patients after antigen-specific stimulation. After TG stimulation, an increased Th17:Th10 ratio was found in HT patients within the naive T cell compartment. Taken together, these data indicate that the thyroid self-antigens TG and TPO induced a skewed Th17:Th10 differentiation in HT patients. IL-6 and TGF-beta have been reported to be important for human Th17 differentiation and, accordingly, HT patients showed higher baseline production of IL-6 and TGF-beta1 than healthy donors. Moreover, the baseline expression of mRNA encoding the transcription factor Forkhead box protein 3 (FOXP3) was similar in HT patients and healthy donors, but HT patients displayed higher constitutive expression of the splice variant FOXP3Delta2, lacking exon 2, than healthy donors. Full-length FOXP3 has been shown to inhibit Th17 differentiation, while FOXP3Delta2 does not. Thus, increased IL-6 and TGF beta1 in the microenvironment and the increased expression of FOXP3Delta2 may contribute to the skewing of Th17 cells in HT patients. In conclusion, the human thyroid self-antigen TG is able to induce antigen-specific production of IL-10 in CD19+ B cells and CD4+ T cells among healthy donors and patients with GD or HT. Our data indicates that patients with GD or HT were not impaired in producing IL 10 and thus an immunoregulatory response. Additionally, TPO, a thyroid self antigen, induced a higher frequency of Th17 cells in HT. This indicates that Th17 cells may play an important role in HT pathogenesis. PMID- 26836806 TI - Benefits and harms of red blood cell transfusions in patients with septic shock in the intensive care unit. AB - BACKGROUND: Transfusion of red blood cells (RBCs) is widely used for non-bleeding patients with septic shock in the intensive care unit (ICU). The evidence for effect and safety are limited showing conflicting results and transfused RBCs have the potential to harm subgroups of critically ill patients. Our aim was to assess the benefits and harms of RBC transfusion in patients with septic shock in a randomised clinical trial and to conduct an up-to-date systematic review with meta-analysis of all randomised clinical trials comparing different transfusion strategies. METHODS: We planned and conducted a randomised, partly blinded, clinical trial assigning patients with septic shock in the ICU and a haemoglobin level of 9 g/dl (5.6 mM) or below to receive single units of pre-storage leukoreduced RBCs at a lower haemoglobin threshold level of 7 g/dl (4.3 mM) or below or a higher haemoglobin threshold level of 9 g/dl (5.6 mM) or below. The primary outcome was death by day 90 after randomisation. Secondary outcomes were need for life support, severe adverse reactions, ischaemic events in the ICU and days alive and out of hospital. Secondly, we conducted a systematic review of randomised controlled trials comparing benefits and harms of using restrictive (range of lower haemoglobin thresholds) versus liberal (range of higher haemoglobin threshold) transfusion trigger strategies to guide RBC transfusion and pooled results in meta-analyses and trial sequential analyses. RESULTS: Of the 1005 patients that underwent randomisation 998 were included in analysis of the primary outcome of mortality. Ninety days after randomisation, 216 of 502 patients (43%) in the lower threshold group had died compared to 223 of 496 (45%) patients in the higher threshold group (relative risk (RR) 0.94, 95% confidence interval (CI) 0.78 to 1.09, p=0.44). The number of patients who required life support, who had ischaemic events, severe adverse reactions and number of days alive and out of hospital were similar in the two groups. Patients in the lower threshold group received 1588 units of RBCs compared to 3088 units in the higher group. A total of 176 (36%) patients in the lower threshold group never received RBCs in the ICU compared with six patients (1%) in the higher threshold group. The systematic review identified 31 trials with a total of 9813 patients in different clinical settings. In meta-analyses restrictive versus liberal transfusion strategies were not associated with the RR of death (0.89, 95% CI 0.76 to 1.05, 5607 patients in eight trials with lower risk of bias), overall morbidity (RR 0.98, 95% CI 0.85 to 1.12, 4517 patients in six trials with lower risk of bias), fatal or non-fatal myocardial infarction (RR 1.32, 95% CI 0.61 to 2.83, 4630 patients in six trials with lower risk of bias). Trial sequential analysis on mortality and myocardial infarction showed that required information sizes had not been reached but use of restrictive transfusion strategies was associated with reduced numbers of RBC units transfused (mean difference -1.43, 95% CI -2.01 to -0.86) and reduced proportion of patients transfused (RR 0.54, 95% CI 0.47 to 0.63). CONCLUSION: The TRISS trial provided evidence for the safe use of 7 g/dl as transfusion trigger in patients with septic shock and reduced the number of units transfused with about half. In line with this, the updated systematic review including data from several recent trials showed no associations with mortality or other adverse events when comparing restrictive to liberal RBC transfusion strategies, however, restrictive transfusion strategies reduce the exposure of patients to RBC transfusions and reduce number of transfused RBC units. Given the fact that liberal transfusion strategies have not been proven beneficial, a more restrictive approach should be considered. Results from the TRISS trial together with other recent trials have the potential to alter the international guidelines for transfusing critically ill patients. Several guidelines have been updated the last years recommending the use of 7-8 g/dl as the ''universal'' trigger level. Patients with acute myocardial ischaemia and patients with acute brain injury may need special considerations. PMID- 26836807 TI - Temporal and Spatial Variations of Drought in China: Reconstructed from Historical Memorials Archives during 1689-1911. AB - In China, Zou Zhe (Memorials to the Throne, or Palace Memorials), an official communication to the emperors of China by local officials, offers an opportunity to reconstruct the spatial-temporal distributions of droughts at a high resolution. A 223-year, 1689-1911, time series of drought events was reconstructed in this study based on 2494 pieces of Zou Zhe. The results show that: 1) on the temporal scale, the drought affected areas, i.e., number of affected counties, showed three peak periods during the last 223 years and nine extreme drought years with more than 300 counties affected have been identified; 2) on the spatial scale, there existed three drought-prone areas in China, i.e., Gansu province and Ningxia Hui Autonomous Region in Northwest China, Shandong, Hebei, and Henan provinces and Tianjin in the North China, and Anhui and Jiangsu provinces in Jianghuai area, respectively; 3) the drought-prone areas have been expanding from North China to South China since the second half of 19th century; 4) on the seasonal scale, summer witnessed the largest number of drought events. Meanwhile, the uncertainties of the results were also discussed, i.e. what caused the spatial-temporal distribution of drought. The results of this study can be used to mitigate the adverse effects of extreme weather events on food increasing and stable production. PMID- 26836808 TI - Trauma-associated bleeding: management of massive transfusion. AB - PURPOSE OF REVIEW: Early treatment goals in the bleeding trauma patient have changed based on recent research findings. Trauma patients requiring a massive transfusion protocol have shown a decreased mortality based on a more aggressive and balanced approach to blood product resuscitation. This chapter will review the recent advances in managing the bleeding trauma patient. RECENT FINDINGS: Recent data have suggested a combined approach of early ratio-based blood product use, bedside viscoelastic hemostatic assays, hemostatic resuscitation, and finally goal-directed therapy to complete resuscitation. SUMMARY: There is now evidence to support the early use of a 1 : 1 : 1 blood product transfusion protocol to restore lost circulating volume, improve oxygen carrying capacity, replace diluted platelets, and replenish clotting factors in massively bleeding trauma patients. Further study is needed to determine whether prehospital initiation of blood products and pharmacological adjuncts will improve outcomes. PMID- 26836809 TI - Relationship of Sulfamethoxazole Therapeutic Drug Monitoring to Clinical Efficacy and Toxicity: A Retrospective Cohort Study. AB - BACKGROUND: Trimethoprim/sulfamethoxazole (TMP/SMX) is the treatment of choice for infections caused by Pneumocystis jiroveci, Stenotrophomonas maltophilia, and Nocardia species, but the utility of therapeutic drug monitoring (TDM) is unclear. The objective of this study was to evaluate the association between peak sulfamethoxazole (SMX) serum levels and clinical outcomes to determine the utility of TDM of TMP/SMX. METHODS: This study was conducted in patients receiving treatment with TMP/SMX for culture-positive infection who underwent TDM from 2003 to 2013. Peak SMX levels were classified as below target (<100 mcg/mL), within target (100-150 mcg/mL), or above target (>150 mcg/mL). The effect of initial SMX levels on clinical outcomes was compared using propensity score adjusted multivariable Cox models. RESULTS: A total of 279 patients had SMX monitoring performed. The primary infecting organisms were P. jiroveci (47%) and S. maltophilia (38%). A majority of patients (74%) had an SMX peak level outside of the target range. Using direct regression propensity score adjustment, there was no significant difference between rates of clinical failure and initial peak SMX level (<100 mcg/mL versus 100-150 mcg/mL: hazard ratio 0.92, 95% confidence interval, 0.28-3.07 and >150 mcg/mL versus 100-150 mcg/mL: hazard ratio 1.92, 95% confidence interval, 0.72-5.09). Similarly, there was no relationship between SMX level and toxicity (P = 0.42). CONCLUSIONS: Sulfamethoxazole serum levels outside the target range were not associated with increased rates of clinical failure in patients treated with TMP/SMX. There was also no association found between peak SMX levels and rates of adverse events. Although this study cannot disprove that dose adjustments after the initial SMX peak level may have affected clinical outcomes, the results suggest that the utility of SMX TDM may be limited to a subset of patients and requires further prospective investigation. PMID- 26836810 TI - Extended-Interval Dosing of Gentamicin Aiming for a Drug-Free Period in Neonates: A Prospective Cohort Study. AB - BACKGROUND: Current gentamicin dosing algorithms in adult populations target a high peak concentration (Cmax) assuring efficacy and a drug-free period (concentration <0.5 mg/L) preventing toxicity. In contrast, gentamicin-based regimens in neonatal sepsis often aim for lower peak levels and trough concentrations of 0.5-2.0 mg.L. The latter concentrations are associated with an increased risk of aminoglycoside-related toxicity. Therefore, the primary aim of this study was to assess the target attainment of a simple and practical dosing regimen designed to attain drug-free periods in newborns. METHODS: The study was of prospective observational design. Neonates admitted to a level II neonatal nursery diagnosed with (suspected) early-onset sepsis and commencing intravenous gentamicin therapy of 5 mg.kg every 36 hours were eligible for inclusion. Gentamicin dosing was guided by drug concentration monitoring targeting Cmax values >8 mg.L and estimated trough concentrations <0.5 mg.L. Relationships between body weight (BW), gestational age (GA), postnatal age, and pharmacokinetic parameters were analyzed using the Pearson correlation test, and univariate and multivariate logistic regression analyses were performed to identify covariates predictive of target attainment failure. RESULTS: A total of 184 patients were included. 90.4% of patients (n = 166) achieved a Cmax value >8 mg.L with a Cmin value <0.5 mg.L. Subsequently, significant correlations were found between GA and Cmax (r = 0.58, P < 0.001) between GA and Cmin (r = 0.44, P < 0.001), between BW and Cmax (r = 0.50, P < 0.001), and between BW and Cmin (r = 0.42, P < 0.001). Correlations between area under the curve (AUC) and GA (r = 0.064, P = 0.4), and between AUC and BW (r = 0.028, P = 0.7) were not significant. During multivariate analysis, only GA (P < 0.001) was retained as an independent predictor of underexposure. CONCLUSIONS: Extended interval dosing of gentamicin resulted in high target attainment rates in neonates admitted to a level II unit. In line with previous reports, low GA and BW were predictive of subtherapeutic peak and toxic trough levels. The AUC, however, was unaffected by the interpatient variation in GA and BW. Since AUC-guided dosing is gaining interest worldwide, the latter finding deserves further exploration in other neonatal cohorts. PMID- 26836811 TI - Combined Administration of Ghrelin and Corticotropin-Releasing Hormone in the Diagnosis of Cushing's Disease. AB - BACKGROUND/AIMS: Exaggerated adrenocorticotropic hormone (ACTH) and cortisol responses to ghrelin in Cushing's disease (CD) have previously been reported, similarly to responses to corticotropin-releasing hormone (CRH). We assessed the ability of ghrelin to enhance ACTH and cortisol responses when added to CRH stimulation in CD patients. METHODS: In 21 CD patients (18 females, 3 males; age 49.8 +/- 10.2 years; BMI 29.8 +/- 0.8) and 8 healthy subjects (7 females, 1 male; age 40.6 +/- 5.3 years; BMI 29.9 +/- 1.2), we administered (1) ghrelin 100 ug i.v. bolus, (2) CRH 100 ug i.v. bolus, and (3) ghrelin + CRH combination. ACTH and cortisol were analyzed by commercially available kits from samples taken at 0, 15, 30, 45, 60, 90 and 120 min. ACTH and cortisol responses were calculated as peak and area under the curve (AUC0-120 min). RESULTS: ACTH and cortisol at baseline and stimulated with ghrelin and/or CRH (peak and AUC0-120 min) were significantly higher in CD patients compared to controls (p < 0.01). ACTH and cortisol responses to ghrelin or CRH were similar in CD patients. Combined ghrelin + CRH administration in CD patients produced the highest ACTH response (peak and AUC0-120 min) compared to ghrelin or CRH alone (p < 0.01). Cortisol responses after ghrelin + CRH were uncoupled with ACTH responses and similar to the response to ghrelin or CRH alone in both groups. ACTH and cortisol responses, during all three tests, were similar in CD patients with micro- or macroadenomas. CONCLUSION: Ghrelin administration causes exaggerated ACTH and cortisol responses in CD patients compared to healthy controls. In combination with CRH, it additionally enhances ACTH secretion without further additive effect on cortisol output. PMID- 26836812 TI - An Analysis of Conjunctival Map Biopsies in Sebaceous Carcinoma. AB - PURPOSE: To evaluate the need for standardized conjunctival map biopsies in periocular sebaceous carcinoma and to formulate recommendations regarding map biopsy number, location, size, and utility based on analysis of biopsy locations, results, and outcomes. METHODS: Retrospective consecutive series of patients with sebaceous carcinoma treated at a tertiary care hospital from 1988 to 2013. Main outcome measures included conjunctival biopsy locations, number, size, and pathology. RESULTS: A diffuse eyelid pattern was evident on presentation in 28/51 patients (54.9%) versus a solitary eyelid nodule in 23/51 (45.1%). Forty-five patients underwent a total of 429 conjunctival biopsies. The conjunctiva was negative in 277 specimens (64.6%), positive in 121 (28.2%), suspicious in 26 (6.1%), and nondiagnostic in 5 (1.2%). Intraepithelial conjunctival involvement was present in 36 patients (70.6%) of whom 23 (63.9%) presented with a diffuse eyelid appearance. There was no statistically significant correlation between primary tumor location and sites of positive biopsies or biopsy size. The pattern at presentation and location of primary tumor did not correlate with biopsy results. Clinical assessment regarding conjunctival involvement was incorrect in 10 of 23 patients (43.5%) with a solitary nodule. Despite primary tumor resection with clear margins confirmed on pathology, 5 of 45 (11%) patients had locally recurrent sebaceous carcinoma. CONCLUSIONS: Conjunctival biopsy size does not correlate with the presence of tumor in the biopsy. Primary tumor location and pattern of tumor at presentation do not correlate with conjunctival biopsy results. Irrespective of the clinical tumor features, standardized conjunctival map biopsies are essential in staging periocular sebaceous carcinoma. PMID- 26836813 TI - Biogenesis of water splitting by photosystem II during de-etiolation of barley (Hordeum vulgare L.). AB - Etioplasts lack thylakoid membranes and photosystem complexes. Light triggers differentiation of etioplasts into mature chloroplasts, and photosystem complexes assemble in parallel with thylakoid membrane development. Plastids isolated at various time points of de-etiolation are ideal to study the kinetic biogenesis of photosystem complexes during chloroplast development. Here, we investigated the chronology of photosystem II (PSII) biogenesis by monitoring assembly status of chlorophyll-binding protein complexes and development of water splitting via O2 production in plastids (etiochloroplasts) isolated during de-etiolation of barley (Hordeum vulgare L.). Assembly of PSII monomers, dimers and complexes binding outer light-harvesting antenna [PSII-light-harvesting complex II (LHCII) supercomplexes] was identified after 1, 2 and 4 h of de-etiolation, respectively. Water splitting was detected in parallel with assembly of PSII monomers, and its development correlated with an increase of bound Mn in the samples. After 4 h of de-etiolation, etiochloroplasts revealed the same water-splitting efficiency as mature chloroplasts. We conclude that the capability of PSII to split water during de-etiolation precedes assembly of the PSII-LHCII supercomplexes. Taken together, data show a rapid establishment of water-splitting activity during etioplast-to-chloroplast transition and emphasize that assembly of the functional water-splitting site of PSII is not the rate-limiting step in the formation of photoactive thylakoid membranes. PMID- 26836815 TI - Determining preventability of pediatric readmissions using fault tree analysis. AB - BACKGROUND: Previous studies attempting to distinguish preventable from nonpreventable readmissions reported challenges in completing reviews efficiently and consistently. OBJECTIVES: (1) Examine the efficiency and reliability of a Web based fault tree tool designed to guide physicians through chart reviews to a determination about preventability. (2) Investigate root causes of general pediatrics readmissions and identify the percent that are preventable. DESIGN/SETTING/PATIENTS: General pediatricians from The Children's Hospital of Philadelphia used a Web-based fault tree tool to classify root causes of all general pediatrics 15-day readmissions in 2014. INTERVENTION/MEASUREMENTS: The tool guided reviewers through a logical progression of questions, which resulted in 1 of 18 root causes of readmission, 8 of which were considered potentially preventable. Twenty percent of cases were cross-checked to measure inter-rater reliability. RESULTS: Of the 7252 discharges, 248 were readmitted, for an all cause general pediatrics 15-day readmission rate of 3.4%. Of those readmissions, 15 (6.0%) were deemed potentially preventable, corresponding to 0.2% of total discharges. The most common cause of potentially preventable readmissions was premature discharge. For the 50 cross-checked cases, both reviews resulted in the same root cause for 44 (86%) of files (kappa = 0.79; 95% confidence interval: 0.60-0.98). Completing 1 review using the tool took approximately 20 minutes. CONCLUSION: The Web-based fault tree tool helped physicians to identify root causes of hospital readmissions and classify them as either preventable or not preventable in an efficient and consistent way. It also confirmed that only a small percentage of general pediatrics 15-day readmissions are potentially preventable. Journal of Hospital Medicine 2016;11:329-335. (c) 2016 Society of Hospital Medicine. PMID- 26836816 TI - Supramolecular Explorations: Exhibiting the Extent of Extended Cationic Cyclophanes. AB - Acting as hosts, cationic cyclophanes, consisting of pi-electron-poor bipyridinium units, are capable of entering into strong donor-acceptor interactions to form host-guest complexes with various guests when the size and electronic constitution are appropriately matched. A synthetic protocol has been developed that utilizes catalytic quantities of tetrabutylammonium iodide to make a wide variety of cationic pyridinium-based cyclophanes in a quick and easy manner. Members of this class of cationic cyclophanes with boxlike geometries, dubbed Ex(n)Boxm(4+) for short, have been prepared by altering a number of variables: (i) n, the number of "horizontal" p-phenylene spacers between adjoining pyridinium units, to modulate the "length" of the cavity; (ii) m, the number of "vertical" p-phenylene spacers, to modulate the "width" of the cavity; and (iii) the aromatic linkers, namely, 1,4-di- and 1,3,5-trisubstituted units for the construction of macrocycles (ExBoxes) and macrobicycles (ExCages), respectively. This Account serves as an exploration of the properties that emerge from these structural modifications of the pyridinium-based hosts, coupled with a call for further investigation into the wealth of properties inherent in this class of compounds. By variation of only the aforementioned components, the role of these cationic receptors covers ground that spans (i) synthetic methodology, (ii) extraction and sequestration, (iii) catalysis, (iv) molecular electronics, (v) physical organic chemistry, and (vi) supramolecular chemistry. Ex(1)Box(4+) (or simply ExBox(4+)) has been shown to be a multipurpose receptor capable of binding a wide range of polycyclic aromatic hydrocarbons (PAHs), while also being a suitable component in switchable mechanically interlocked molecules. Additionally, the electronic properties of some host-guest complexes allow the development of artificial photosystems. Ex(2)Box(4+) boasts the ability to bind both pi-electron-rich and -poor aromatic guests in different binding sites located within the same cavity. ExBox2(4+) forms complexes with C60 in which discrete arrays of aligned fullerenes result in single cocrystals, leading to improved material conductivities. When the substitution pattern of the Ex(n)Box(4+) series is changed to 1,3,5-trisubstituted benzenoid cores, the hexacationic cagelike compound, termed ExCage(6+), exhibits different kinetics of complexation with guests of varying sizes-a veritable playground for physical organic chemists. The organization of functionality with respect to structure becomes valuable as the number of analogues continues to grow. With each of these minor structural modifications, a wealth of properties emerge, begging the question as to what discoveries await and what properties will be realized with the continued exploration of this area of supramolecular chemistry based on a unique class of receptor molecules. PMID- 26836817 TI - The recurrence risk of placenta accreta following uterine conserving management. AB - BACKGROUND: Placenta accreta is a condition of abnormal placental attachment that was usually treated by hysterectomy. Techniques to conserve the uterus are now commonly used and series of subsequent pregnancy outcomes have been reported. The recurrence risk of placenta accreta is now a relevant detail and is currently not known. This work was performed to calculate the recurrence risk by reviewing the published literature. METHODS: A literature search using the terms "placenta accreta", "placenta percreta", "placenta increta", "abnormal placental attachment" and "placental attachment disorder" followed by hand-searching identified 6 papers that contained data concerning recurrence of placenta accreta in subsequent pregnancies following initial conservative treatment. RESULTS: Overall 407 pregnancies were recorded and 85.7% of women reported achieved a subsequent pregnancy following conservative treatment. The risk of recurrence of placental attachment disorder in a subsequent pregnancy was 19.9% (weighted mean, 95% CI 12.2-27.7). CONCLUSIONS: The recurrence risk of placental attachment disorder following uterine conservation treatments is 20% . This risk should be discussed with women with an antenatal diagnosis of a placental attachment disorder who may be considering uterine conservation in order to retain the option of a future pregnancy. PMID- 26836818 TI - Influenza and its treatment during pregnancy: A review. AB - The influenza viral infection has dramatic effects during pregnancy on the mother and the fetus. We present a review article on the prevention and treatment recommendations of influenza infection in pregnant women, and the effects of antiviral medications on maternal-fetal outcomes. This viral infection not only leads to miscarriages, preterm deliveries and a high maternal mortality rate, but it also poses negative risks to the fetus including small-for-gestational age infants, and admissions to neonatal intensive care units. Vaccination is the most effective strategy for preventing influenza infection during pregnancy whereby can protect both maternal and fetal immunities. The safety profiles of antiviral drugs during pregnancy are limited. Available risk-benefit evidence has indicated that pregnant women with suspected or confirmed influenza should receive prompt antiviral therapy where these medications reduce the risk of complications among pregnant women, and attenuate the teratogenic effects of the influenza infection. Post-exposure prophylaxis is not recommended for most pregnant women, but it may be prescribed in pandemic settings, particularly to non-vaccinated women. Although some ex vivo models for pharmacokinetic studies have revealed that the transplacental transfer of oseltamivir to fetal circuits may occur, there is no evidence of adverse fetal outcomes as a result of most in utero exposures to neuraminidase inhibitors. Due to the large number of confounding variables, large, population-based studies are needed to assess the association between in utero oseltamivir exposure and fetal outcome. PMID- 26836819 TI - Neonatal intensive care unit discharge of infants with cardiorespiratory events: Tri-country comparison of academic centers. AB - OBJECTIVE: Compare how NICUs within academic centers in Canada, France, and the United States make discharge decisions regarding cardiorespiratory recordings and home use of apnea monitors, oximeters and caffeine. STUDY DESIGN: An anonymous survey was sent to neonatologists through the member listserv of the American Academy of Pediatrics Section on Perinatal Pediatrics, the Canadian Fellowship Program Directory, and to Level 3 NICUs in France. RESULTS: The response rates were 89% , 83% , and 79% for US, Canada and France respectively. In Canada, 45% perform pre-discharge recordings vs. 38% in France and 24% in the US. Apnea free days prior to discharge were required in 100% of centers in Canada, 96% in France, and 92% in the US. In Canada and France, 65% and 68% of units discharge patients on monitors vs. 99% in the US. 64% of the US centers sometimes use home caffeine compared to 40% in Canada and 34% in France. Over 60% of the centers in Canada and France wait until at least 40 weeks post menstrual age to discharge patients, whereas only about 33% of the US wait that late to discharge patients. CONCLUSIONS: Discharge practices from NICUs are not well standardized across institutions or countries. Canada and France keep infants in the hospital longer and are less likely than the US to use home monitoring and home caffeine. PMID- 26836814 TI - Unique features of a global human ectoparasite identified through sequencing of the bed bug genome. AB - The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human-bed bug and symbiont-bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite. PMID- 26836820 TI - Effects of intermittent hypoxia and hyperoxia on angiogenesis and lung development in newborn mice. AB - BACKGROUND: Premature birth disrupts hypoxia driven microvascular development that directs alveolar and lung growth. Changes in oxygen exposure after birth can perturb the regulation of angiogenesis leading to bronchopulmonary dysplasia (BPD). We studied the effects of intermittent hypoxia or hyperoxia on HIF and angiogenic gene expression and lung development in newborn mice. METHODS: Newborn litters were randomized within 12 h of birth to 12% O2 (4 h), 50% O2 (4 h) or 12% O2 (2 h)/50% O2 (2 h) followed by room air (RA) recovery for 20 h. Mice in RA were the control group. The mice were exposed to 6 such cycles (D1-D6) and sacrifice on D7. Whole lung mRNA was isolated and gene expression performed by qRT-PCR (HIF1alpha/2alpha/1beta; PHD2, Ang1, Tie2, Vegf, VegfR1 & VegfR2) and analyzed by PCR array data analysis web portal. HIF-1alpha, prolyl hydroxylase-2 and VEGF protein were analyzed in whole lung by ELISA. Lung morphology was assessed by H&E sections and radial alveolar counts; cell proliferation by Ki67 immunostaining. RESULTS: HIF-1alpha mRNA and VEGF protein were significantly downregulated in the 50% O2 group; VEGF mRNA and protein were significantly downregulated in the 12% O2-50% O2 group; Ang-1 and its receptor mRNA expression were downregulated in 12% O2 and 12% O2-50% O2 groups. 50% O2 (hyperoxia) and 12% O2-50% O2 (hypoxia-hyperoxia) groups demonstrated alveolar simplification by RAC and the same groups had decreased cell proliferation by Ki67 staining compared to RA and hypoxia (12% O2) groups. CONCLUSIONS: Downregulation of HIF and angiogenic gene expression with associated changes in lung histology following intermittent hypoxia-hyperoxia is likely an important contributing factor in the development of BPD. PMID- 26836821 TI - Pulmonary hypertension predicts mortality in infants with omphalocele. AB - OBJECTIVE: The objective of this study was to identify predictors of mortality in infants with omphalocele. METHODS: Medical records of infants with omphalocele born between January 1992 and June 2012, with follow-up toDecember 2012, were retrospectively reviewed. Survivors and non-survivors were compared. Evidence for pulmonary hypertension was sought between the second and seventh day after birth. All included infants had increased right ventricular pressures (RVP >40 mmhg) on echocardiogram on the second day of life with increased oxygen requirements, therefore, the finding of increased pressure was not considered a result of the transitional circulation. Logistic regression was used to evaluate the importance and independence of various factors. RESULTS: Of 51 infants whose records were reviewed, 13 died (25%) and 38 survived (75%). The median time to death was 34 days (range: 4 -408 days). The median follow-up time for those who died was 1.5 years (range: 0.01-15 years) and for survivors was 2.6 years (range: 0.08-15 years). Logistic regression revealed that respiratory insufficiency at birth (OR: 14.8; 95% CI: 2.5-85.0) and pulmonary hypertension (OR: 6.4; 95% CI: 1.1-39.0) were independently associated with mortality. CONCLUSION: Respiratory insufficiency after birth and pulmonary hypertension are independent predictors of mortality in infants with omphalocele. PMID- 26836822 TI - Weight gain and hypertension at three years of age and older in extremely low birth weight infants. AB - OBJECTIVE: To determine the prevalence and weight gain as a risk factor of hypertension (HTN) at three years of age and older among extremely low birth weight (ELBW) infants. STUDY DESIGN: Retrospective cohort study of all ELBW infants born and followed up at our institution over 15 years. RESULTS: 204 infants were followed up for [median (inter-quartile range)] 10.2 years (6.9 13.0). Their birth weight and gestational age were (mean+/-standard deviation) 758+/-149 g and 26.4+/-2.1 weeks respectively. At 3 years of age and older, the prevalence of HTN was 7.3% (15/204), and the prevalence of obesity was 13.2% (27/204). Obesity was more prevalent in children with than without HTN [33% (5/15) vs. 12% (22/189); p = 0.01]. In a regression analysis, body mass index (BMI) percentile at 3 years of age and older (p = 0.04) and increase in weight Z scores since birth (p = 0.008) were associated with a higher systolic blood pressure (SBP; R = 0.386, p < 0.001). CONCLUSION: Obesity is prevalent in ELBW infants at three years of age and older, and it is significantly associated with hypertension. An increase in BMI percentile at >=3 years of age, and the rate of weight gain since birth among ELBW infants are associated with an increase in SBP. PMID- 26836823 TI - Hepatitis C Virus universal screening versus risk based selective screening during pregnancy. AB - OBJECTIVES: We sought to compare the value of HCV universal screening versus risk based selective screening in pregnant women. STUDY DESIGN: In a prospective observational study (Jan 2012 - March 2012), pregnant women, in a high risk inner city clinic, who were at "low risk" for HCV infection were tested for HCV antibodies (universal screening) and their medical records were compared to the medical records of pregnant women who were at "high risk" (risk based selective screening as assessed by their obstetricians' screening questionnaire). RESULTS: During the study period, 419 women delivered at our institution with 8.8% (37/419) at high risk for HCV. In 95% (183/193) of available and consenting low risk women, HCV antibody testing was done. The prevalence of HCV was 3.18% (7/220; 95% CI: 1.36-6.50) in all tested women versus 0.95% (4/419; 95% CI: 0.31 2.59) in risk-based selectively tested women. Overall the screening questionnaire had a sensitivity of 0.85 (0.42-0.99) and a specificity of 0.52 (0.45-0.58) in all women who had HCV antibody testing and questionnaire screening. CONCLUSIONS: Using a screening questionnaire to identify women at risk for HCV infection during pregnancy under-estimates the real prevalence of HCV. A universal screening should be considered in high risk cities. PMID- 26836824 TI - Neonatal hemochromatosis in monochorionic twins. AB - Neonatal hemochromatosis (NH) is a form of neonatal liver failure caused by maternal-fetal alloimmune injury to hepatocytes. The etiology of neonatal hemochromatosis is not exactly understood. However, according to one theory neonatal hemochromatosis is believed to be an alloimmune disorder causing liver injury in the fetus. In order to diagnose neonatal hemochromatosis there are some criteria that should be taken into account, such as positive family history, high serum ferritin levels, high serum alpha-fetoprotein levels and siderosis demonstrated by histology or with magnetic resonance.We present a case of a monochorionic newborn twin who applied to our hospital with sepsis clinical symptoms like clinics, was diagnosed with NH and immediately treated with antioxidant therapy while the other twin with same clinical symptoms did not respond to therapy and passed away. NH should be considered in the differential diagnosis of cases with sepsis-like clinical symptoms that do not respond to antibiotics; early antioxidant therapy in these cases is lifesaving. PMID- 26836825 TI - Phototherapy induced cutaneous eruption in a neonate with transient porphyrinemia. AB - Phototherapy for hyperbilirubinemia has rare complications. We report a case of phototherapy induced eruption in a neonate with transient porphyrinemia. Our patient received phototherapy due to hyperbilirubinemia secondary to erythroblastosis fetalis (hemolytic disease of the newborn). He developed a cutaneous rash in the light-exposed areas of his skin. Erythrocyte and plasma porphyrins were elevated at the time. Phototherapy induced eruption with a transient porphyrinemia is rare. Upon review of the literature, we found only 5 other cases of patients with phototherapy induced rash and elevated porphyrins reported. We compared the five other reported cases to our case, looking at drug exposure, age, and receipt of exchange transfusion. CONCLUSION: While this is an uncommon occurrence, transient porphyrinemia should be considered in neonates with phototherapy induced cutaneous eruption and erythroblastosis fetalis. PMID- 26836826 TI - Determining the prevalence of cytomegalovirus infection in a cohort of preterm infants. PMID- 26836829 TI - Coordination Complexes of Transition Metals (M = Mo, Fe, Rh, and Ru) with Tin(II) Phthalocyanine in Neutral, Monoanionic, and Dianionic States. AB - The ability of tin atoms to form stable Sn-M bonds with transition metals was used to prepare transition metal complexes with tin(II) phthalocyanine in neutral, monoanionic, and dianionic states. These complexes were obtained via the interactions of [Sn(IV)Cl2Pc(3-)](*-) or [Sn(II)Pc(3-)](*-) radical anions with {Cp*Mo(CO)2}2, {CpFe(CO)2}2, {CpMo(CO)3}2, Fe3(CO)12, {Cp*RhCl2}2, or Ph5CpRu(CO)2Cl. The neutral coordination complexes of Cp*MoBr(CO)2[Sn(II)Pc(2 )].0.5C6H4Cl2 (1) and CpFe(CO)2[Sn(II)Pc(2-)].2C6H4Cl2 (2) were obtained from [Sn(IV)Cl2Pc(3-)](*-). On the other hand, the coordination of transition metals to [Sn(II)Pc(3-)](*-) yielded anionic coordination complexes preserving the spin on [Sn(II)Pc(3-)](*-). However, in the case of {cryptand[2,2,2](Na(+))}{CpFe(II)(CO)2[Sn(II)Pc(4-)]}(-).C6H4Cl2 (4), charge transfer from CpFe(I)(CO)2 to [Sn(II)Pc(3-)](*-) took place to form the diamagnetic [Sn(II)Pc(4-)](2-) dianion and {CpFe(II)(CO)2}(+). The complexes {cryptand[2,2,2](Na(+))}{Fe(CO)4[Sn(II)Pc(3-)](*-)} (5), {cryptand[2,2,2](Na(+))}{CpMo(CO)2[Sn(II)Pc(2-)Sn(II)Pc(3-)(*-)]} (6), and {cryptand[2,2,2](Na(+))}{Cp*RhCl2[Sn(II)Pc(3-)](*-)} (7) have magnetic moments of 1.75, 2.41, and 1.75 MU(B), respectively, owing to the presence of S = 1/2 spins on [Sn(II)Pc(3-)](*-) and CpMo(I)(CO)2 (for 6). In addition, the strong antiferromagnetic coupling of spins with Weiss temperatures of -35.5 -28.6 K was realized between the CpMo(I)(CO)2 and the [Sn(II)Pc(3-)](*-) units in 6 and the pi-stacking {Fe(CO)4[Sn(II)Pc(3-)](*-)}2 dimers of 5, respectively. The [Sn(II)Pc(3-)](*-) radical anions substituted the chloride anions in Ph5CpRu(CO)2Cl to form the formally neutral compound {Ph5CpRu(II)(CO)2[Sn(II)Pc(3 )]} (8) in which the negative charge and spin are preserved on [Sn(II)Pc(3-)](* ). The strong antiferromagnetic coupling of spins with a magnetic exchange interaction J/k(B) = -183 K in 8 is explained by the close packing of [Sn(II)Pc(3 )](*-) in the pi-stacked {Ph5CpRu(II)(CO)2[Sn(II)Pc(3-)](*-)}2 dimers. PMID- 26836830 TI - A Novel Mutation in DMD (c.10797+5G>A) Causes Becker Muscular Dystrophy Associated with Intellectual Disability. AB - BACKGROUND: Severe intellectual disability has been reported in a subgroup of patients with Duchenne muscular dystrophy but is not typically associated with Becker muscular dystrophy. PATIENT: The authors report a 13-year-old boy, with severe intellectual disability (Wechsler Intelligence Scales for Children-IV, Full Scale IQ < 0.1 percentile), attention-deficit hyperactivity disorder, and mild muscle weakness. He had elevated serum creatine kinase and dystrophic changes on muscle biopsy. Dystrophin immunohistochemistry revealed decreased staining with the C-terminal and mid-rod antibodies and essentially absent staining of the N-terminal immunostain. Sequencing of muscle mRNA revealed aberrant splicing due to a c.10797+5G > A mutation in DMD. CONCLUSION: Dystrophinopathy may be associated with predominantly cognitive impairment and neurobehavioral disorder, and should be considered in the differential diagnosis of unexplained cognitive or psychiatric disturbance in males. PMID- 26836831 TI - Adolescent Depression-Pharmacotherapy or Psychotherapy? PMID- 26836832 TI - Evaluating neuropathic complaints by DN4 and LANSS scales after local corticosteroid therapy in carpal tunnel syndrome. AB - BACKGROUND/PURPOSE: The purpose of this study was to evaluate the neuropathic symptoms after local steroid injection in CTS. Since 2001, neuropathic pain scales have been used in the assessment and follow-up of neuropathic pain. DN4 and LANSS pain questionnaires have been applied to groups, mostly consisted of radiculopathy and polyneuropathy cases, before and after various treatments and the results have been compared with the electrophysiologic findings. However to our knowledge there is yet no such study focusing on neuropathic complaints and the relationship between neuropathic pain and electrophysiological findings before and after local corticosteroid injection. METHODS: Forty-one patients aged 22-65 years and diagnosed with carpal tunnel syndrome by nerve conduction studies who were also found to have neuropathic symptoms were included in the study. All patients received local steroid injection into the carpal tunnel while the questionnaires and nerve conduction studies were performed before and 2 months after the injection. RESULTS: Local steroid injection was found effective on clinical and electrophysiologic parameters as well as on DN4 and LANSS scores in CTS patients (p< 0.05). Electrophysiologic severity exhibited no statistically significant relationship with DN4 and LANSS scores, before and after treatment (p> 0.05). CONCLUSION: These findings suggests that the treatment of neuropathic complaints should be planned independently from the electrophysiologic findings and minimally invasive local steroid injection appears to be effective with regard to clinical and electrophysiologic aspects in CTS patients with neuropathic complaints. PMID- 26836833 TI - Multi-disciplinary Orthopaedics Rehabilitation Empowerment (MORE) program: A new standard of care for injured workers in Hong Kong. AB - BACKGROUND: The objective of this study is to evaluate the effects of the Multi disciplinary Orthopaedics Rehabilitation Empowerment (MORE) Program on reducing chronic disability among injured workers and improving efficiency of work rehabilitation process. METHODS: A cohort of patients with workplace injuries in the lower back were recruited from orthopaedics clinics and assigned to either MORE group (n= 139) or control group (n= 106). Patients in MORE group received an early MRI screening and a coordinated multi-disciplinary management, while patients in the control group received conventional care. Outcome variables are time to return-to-work (RTW) from date of injury, waiting time for MRI screening and time to medical assessment board (MAB). RESULTS: Patients in the MORE Program had significantly shorter duration for RTW (MORE: 6.1 months, CONTROL: 12.8 months, p< 0.01), and more RTW cases (n= 64, 46.0%) compared to CONTROL group (n= 29, 27.4%). The MORE group also had much shorter waiting time for MRI scans (91.85 vs. 309.2 days, p< 0.001) and MAB referral after MRI scans (97.2 vs. 178.9 days, p= 0.001) compared to CONTROL group. CONCLUSIONS: The MORE Program which emphasizes early intervention and early MRI screening, is shown to be effective in shortening sick leave and improving RTW outcomes of injured workers. PMID- 26836834 TI - Orthotic treatment of idiopathic hyperkyphosis with Milwaukee brace. AB - BACKGROUND: Hyperkyphosis with unknown reason is common in teenagers and can be corrected by orthotic management. OBJECTIVES: Investigation of orthotic outcomes by Milwaukee brace. METHODS: Sixty-one patients with idiopathic hyperkyphosis (> 45 degrees) were given Milwaukee brace before skeletal maturity. Hyperkyphosis was measured during the first visit without brace, in-brace, at the end of full time and part time duration of treatment. After treatment completion, participants were categorized in two groups: with hyperkyphosis of 45 degrees and less (Group I) and more than 45 degrees (Group II). These groups were compared to interpret the treatment outcomes. RESULTS: The mean kyphotic curve was 60.1 (SD +/- 7.7) and 71 (SD = 10.1) degrees in Group I and II, respectively. The mean kyphotic curve at the time of full time and part time duration of treatment showed no significant difference in patients successfully completed the treatment (P = 0.10) while there was a significant difference between mean kyphotic curve in full time and part time treatment duration for patients with hyperkyphosis of more than 45 degrees (P < 0.05). CONCLUSIONS: Hyperkyphosis of less than 70 degrees can be treated if the in-brace correction is saved in part-time duration. PMID- 26836835 TI - Effects of hand grip exercise on shoulder joint internal rotation and external rotation peak torque. AB - BACKGROUND AND OBJECTIVES: The goal of this study is to analyze the effects of hand grip training on shoulder joint internal rotation (IR)/external rotation (ER) peak torque for healthy people. METHODS: The research was conducted on 23 healthy adults in their 20 s-30 s who volunteered to participate in the experiment. Hand grip power test was performed on both hands of the research subjects before/after the test to study changes in hand grip power. Isokinetic machine was used to measure the concentric IRPT (internal rotation peak torque) and concentric ERPT (external rotation peak torque) at the velocity of 60 degrees /sec, 90 degrees /sec, and 180 degrees /sec before/after the test. Hand grip training was performed daily on the subject's right hand only for four weeks according to exercise program. Finally, hand grip power of both hands and the maximum torque values of shoulder joint IR/ER were measured before/after the test and analyzed. RESULTS: There was a statistically significant difference in the hand grip power of the right hand, which was subject to hand grip training, after the experiment. Also, statistically significant difference for shoulder ERPT was found at 60 degrees /sec. CONCLUSION: Hand grip training has a positive effect on shoulder joint IRPT/ERPT and therefore can help strengthen muscles around the shoulder without using weight on the shoulder. Consequently, hand grip training would help maintain strengthen the muscles around the shoulder in the early phase of rehabilitation process after shoulder surgery. PMID- 26836836 TI - Investigation of the relationship between kinesiophobia, physical activity level and quality of life in patients with chronic low back pain1. AB - OBJECTIVE: The aim of our study is to examine the relationship between kinesiophobia (fear of movement), physical activity level and quality of life. METHODS: In this study, we assessed 112 patients consulting for low back pain (LBP) of >= 3 month's duration. We used Visual Analog Scale (VAS) for pain intensity, the International Physical Activity Questionnaire (IPAQ) for physical activity level, Tampa Kinesiophobia Scale for perception of kinesiophobia, Oswestry Disability Index for disability status of low back. RESULTS: The results of this study, there was no statistically significant correlation between International Physical Activity Questionnaire, duration of pain, intensity of pain at rest and Tampa Kinesiophobia Scale (p> 0.05). It was found a statistically significant correlation between pain intensity at activity (p= 0.009), disability level (p= 0.000) and Tampa Kinesiophobia Scale. Tampa Kinesiophobia Scale were highly negative correlated with sub-scale of SF-36 Quality of Life Index (general health, physical function, social status, bodily pain, role limitations due to physical health) (p= 0.000). CONCLUSION: The kinesiophobia adversely affect the quality of life limiting the physical activity status of patients with chronic low back pain. PMID- 26836837 TI - Magnitude of muscle activity of the lumbar multifidus using the Core-Noodle device with varied upper extremity postures. AB - BACKGROUND: Lumbar Multifidus (LM) exercise is a treatment in patients with low back pain. We designed a new exercise using device ''Core-Noodle'' (Copyright has been observed in Japan). OBJECTIVE: The purpose of this study was to record the electromyographic (EMG) activity of the lumbar multifidus during a novel exercise. METHODS: Twenty-one healthy young volunteers performed the LM exercise using Core-Noodle in three conditions: no-weight (NW), 1 kg weight (1W), 2 kg weight (2W). This exercise was performed in supine with left shoulder abduct 90 degrees and right shoulder flexed 90 degrees. EMG activity was recorded from surface electrodes on the LM and the thoracic part of the iliocostalis lumborum (ICLT), and normalized to values derived from maximal isometric trials (%MVIC). In addition, the ratio of the LM to ICLT (L/G ratio) was calculated to compare selectivity of LM activity. One-way ANOVA and Bonferroni method were used to draw comparisons among the three conditions. RESULTS: Muscle activation of LM was gradually increased in proportion to the loading dose. L/G ratio increased by weight loading significantly, but slightly decreased at 2W. CONCLUSIONS: The results suggest that characteristic EMG patterns of LM ''selective contraction'' and ''adjustment of load'' are obtained concurrently. PMID- 26836838 TI - The prevalence differences of musculoskeletal problems and related physical workload among hospital staff. AB - BACKGROUND: The musculoskeletal problems (MSP) vary among different occupations since they had different characteristics and physical workloads. Therefore, it is important to know the difference between the occupational groups to design preventing physiotherapy interventions. OBJECTIVE: To investigate the prevalence differences of MSPs and related physical workload among hospital staff. METHODS: In this cross-sectional study, 416 hospital staff completed the Nordic Musculoskeletal Questionnaire for MSP and Physical Workload Questionnaire for assessing the physical workload. RESULTS: One-year prevalence of low back, neck, upper back, and shoulders were 73.8%, 59.9%, 59.4%, and 52.2%, respectively. The most preventing MSPs from work found in the low back (39.2%), upper back (26.7%), and the neck (24.5%). MSP of low back impacted nurses the most with a 1-year prevalence of 81.3% and 57.1% of nurses were prevented from working. Nurses, service and cleaning staff had significantly more physical workload than secretaries and physicians. CONCLUSIONS: MSP of low back had the highest prevalence among hospital staff and it was the leading cause which prevented from working. Nurses were the most in danger in terms of MSPs among hospital staff. Physical workload was significantly higher in nurses, service and cleaning staff than secretaries and physicians. PMID- 26836839 TI - Scapulothoracic muscle strength in individuals with neck pain. AB - BACKGROUND: People with neck pain often present with weakness in the scapulothoracic muscles. Few studies have examined lower trapezius (LT), middle trapezius (MT) and serratus anterior (SA) muscle strength in individuals with neck pain, nor compared strength to asymptomatic individuals. OBJECTIVES: The aim of this study was to examine LT, MT and SA muscle strength in individuals with chronic neck pain. METHODS: Descriptive cross sectional design. Twenty two individuals with chronic neck pain and 17 asymptomatic individuals were included. Participants were asked to complete a screening questionnaire, Neck Disability Index, and underwent manual muscle testing for the LT, MT, and SA muscles bilaterally. Data analyses included paired and comparative independent t-tests. RESULTS: For individuals with neck pain, significant within subject differences in strength between sides for the LT (P< 0.01) and MT (P< 0.01) were present. In contrast, no within subject difference between sides for the asymptomatic group was found for any muscle. Individuals with neck pain were significantly weaker than asymptomatic individuals for the LT (p= 0.02), MT (p= 0.03), and SA (p= 0.01) on their side of neck pain, but not on their non-painful side. CONCLUSIONS: Significant within subject differences were found between sides for the LT and MT while significant between group differences were identified for all three muscles tested. PMID- 26836840 TI - The effects of whole body vibration on EMG activity of the upper extremity muscles in static modified push up position. AB - BACKGROUND: Whole Body Vibration (WBV) has been reported to change neuromuscular activity which indirectly assessed by electromyography (EMG). Although researches regarding the influence of WBV on EMG activity of the upper extremity muscles are in their infancy, contradictory findings have been reported as a result of dissimilar protocols. OBJECTIVE: The purpose of this study was to investigate the effects of WBV on electromyography (EMG) activity of upper extremity muscles in static modified push up position. METHODS: Forty recreationally active females were randomly assigned in WBV and control groups. Participants in WBV group received 5 sets of 30 seconds vibration at 5 mm (peak to peak) and 30 Hz by using vibratory platform. No vibration stimulus was used in the control group. Surface EMG was recorded from Upper Trapezius (UT), Serratus Anterior (SA), Biceps Brachii (BB) and Triceps Brachii (TB) muscles before, during and after the vibration protocol while the subjects maintained the static modified push up position. EMG signals were expressed as root mean square (EMGrms) and normalized by maximum voluntary exertion (MVE). RESULTS: EMGrms activity of the studied muscles increased significantly during the vibration protocol in the WBV group comparing to the control group (P <= 0.05). The results indicated that vibration stimulus transmitting via hands increased muscle activity of UT, SA, BB and TB muscles by an average of 206%, 60%, 106% and 120%, respectively, comparing to pre vibration values. CONCLUSIONS: These findings suggest that short exposure to the WBV could increase the EMGrms activity of the upper extremity muscles in the static modified push-up position. However, more sessions of WBV application require for a proper judgment. PMID- 26836841 TI - Back pain beliefs in adolescents and adults in Australasia: A cross-sectional pilot study of selected psychometric properties of paper-based and web-based questionnaires in two diverse countries. AB - BACKGROUND: It is unknown whether questionnaires measuring psychosocial constructs related to low back pain (LBP) that were originally designed for adults are suitable for adolescents, and if paper and web-versions have similar measurement properties. OBJECTIVES: To examine selected psychometric properties for the paper- and web-based Back-Beliefs Questionnaire (BBQ) and the Fear Avoidance Beliefs Questionnaire (FABQ-phys) among adults and adolescents in two diverse countries and to determine whether differences existed between countries and pain groups. METHODS: A sample of 156 adults (Hong Kong, n= 75; Australia, n= 81) and 96 adolescents (Hong Kong, n= 61; Australia, n= 35) participated in this cross-sectional study. RESULTS: Main effects for country and administration mode were observed in adult BBQ scores, where Australian adults reported significantly higher BBQ scores than Hong Kong adults (mean difference (MD); 95% CI: 2.85; 0.96 4.74) and significantly higher scores were recorded on the web mode compared to the paper mode (MD 0.74; 0.10-1.38). Similarly, Hong Kong adults and adolescents reported higher FABQ-phys scores than Australian adults and adolescents (MD; 95% CI: 3.40; 1.37-5.43 and 4.88; 0.53-9.23, respectively). Internal consistency values were mostly acceptable (alpha >= 0.7). CONCLUSION: Differences exist between cultures for LBP-related beliefs. The BBQ and FABQ-phys have acceptable measurement properties in both administration modes. PMID- 26836842 TI - Preoperative and postoperative serial assessments of postural balance and fall risk in patients with arthroscopic anterior cruciate ligament reconstruction. AB - BACKGROUND: Impaired postural balance due to somatosensory data loss with mechanical instability has been shown in patients with ACL deficiency. OBJECTIVE: To assess postural balance in patients with ACL insufficiency prior to surgery and following reconstruction with serial evaluations. METHODS: Thirty patients (mean age of 27.7 +/- 6.7 years) who underwent arthroscopic reconstruction of ACL with bone-patellar tendon-bone autograft were examined for clinical and functional variables at preoperative day and postoperative 12th week. Posturographic analysis were performed by using Tetrax Interactive Balance System (Sunlight Medical Ltd, Israel) at preoperative day, at 4th, 8th, and 12th weeks following reconstruction. Data computed by posturographic software by the considerations of the oscillation velocities of body sways is fall risk as a numeric value (0-100, lower values indicate better condition). RESULTS: All of the patients (mean age of 27.7 +/- 6.7 years) had significant improvements for clinical, functional evaluations and fall risk (p< 0.05). Mean fall risk was within high-risk category (59.9 +/- 22.8) preoperatively. The highest fall risk was detected at postoperative 4th week. Patients had high fall risk at 8th week similar to preoperative value. Mean fall risk decreased to low level risk at 12th week. Preoperative symptom duration had relationships with preoperative fall risk and postoperative improvement of fall risk (p= 0.001, r= -0.632, p= 0.001, r= 0.870, respectively). The improvement of fall risk was higher in patients with symptoms shorter than 6 months (p= 0.001). CONCLUSIONS: According to these results, mean fall risk of patients with ACL insufficiency was within high risk category preoperatively, and fall risk improves after surgical reconstruction, but as the duration of complaints lengthens especially longer than 6 months, the improvement of fall risk decreases following reconstruction. PMID- 26836843 TI - Facet orientation and tropism: Associations with asymmetric lumbar paraspinal and psoas muscle parameters in patients with chronic low back pain. AB - BACKGROUND: Many studies have explored the relationship between facet tropism and facet joint osteoarthritis, disc degeneration and degenerative spondylolisthesis. However, the associations between facet orientation and tropism, and paraspinal muscles have not been studied. OBJECTIVE: To analyze the associations between facet orientation and tropism, and parameters of paraspinal muscles in patients with chronic low back pain. METHODS: Ninety-five patients with chronic low back pain were consecutively enrolled. Their facet joint angles were measured on computed tomography (CT) while gross cross-sectional area (GCSA), functional cross-sectional area (FCSA) and T2 signal intensity of lumbar paraspinal and psoas muscle were evaluated on magnetic resonance imaging (MRI). RESULTS: The GCSA and FCSA were significantly smaller for multifidus muscle (P< 0.001), but significantly larger for erector spinae and psoas muscles (P< 0.001), in coronally-orientated group than those in sagittally-orientated group. The differences of bilateral GCSA and FCSA of multifidus muscle were significantly larger in facet tropism group than those in no facet tropism group (P= 0.009 and P= 0.019). CONCLUSIONS: Muscular asymmetries may develop in the lumbar region of the spine, which are associated with facet asymmetry in patients with chronic low back pain. Longitudinal studies are needed to understand the causal relationship between facet orientation and tropism and muscular asymmetry in future. PMID- 26836844 TI - Effect of heavy metal co-contaminants on selenite bioreduction by anaerobic granular sludge. AB - This study investigated bioreduction of selenite by anaerobic granular sludge in the presence of heavy metals and analyzed the fate of the bioreduced selenium and the heavy metals. Selenite bioreduction was not significantly inhibited in the presence of Pb(II) and Zn(II). More than 92% of 79 mg/L selenite was removed by bioreduction even in the presence of 150 mg/L of Pb(II) or 400mg/L of Zn(II). In contrast, only 65-48% selenite was bioreduced in the presence of 150-400 mg/L Cd(II). Formation of elemental selenium or selenide varied with heavy metal type and concentration. Notably, the majority of the bioreduced selenium (70-90% in the presence of Pb and Zn, 50-70% in the presence of Cd) and heavy metals (80-90% of Pb and Zn, 60-80% of Cd) were associated with the granular sludge. The results have implications in the treatment of selenium wastewaters and biogenesis of metal selenides. PMID- 26836845 TI - Marinobacter strain NNA5, a newly isolated and highly efficient aerobic denitrifier with zero N2O emission. AB - An efficient aerobic denitrification bacterium, strain NNA5, was isolated and identified as Marinobacter sp. NNA5. NNA5 did not perform heterotrophic nitrification. GC/IRMS analysis revealed that (15)N2 was produced from Na(15)NO2 and K(15)NO3. GC/MS and quantitative analyses showed that no N2O emission occurred when nitrite or nitrate was used as substrate. Single factor experiments indicated that optimal conditions for aerobic denitrification were: sodium succinate or sodium pyruvate as carbon source, temperature 35 degrees C, NaCl concentration 2-4%, C/N ratio 6-8, pH 7.5, rotation speed 150 rpm (giving dissolved oxygen concentration 6.08 mg/L), NO3(-)-N concentration ranging from 140 to 700 mg/L. NNA5 displayed highly efficient aerobic denitrifying ability, with maximal NO3(-)-N removal rate 112.8 mg/L/d. In view of its ability to perform aerobic denitrification with zero N2O emission, NNA5 has great potential for future application in aerobic denitrification processes in industrial and aquaculture wastewater treatment systems. PMID- 26836846 TI - Biogas crops grown in energy crop rotations: Linking chemical composition and methane production characteristics. AB - Methane production characteristics and chemical composition of 405 silages from 43 different crop species were examined using uniform laboratory methods, with the aim to characterise a wide range of crop feedstocks from energy crop rotations and to identify main parameters that influence biomass quality for biogas production. Methane formation was analysed from chopped and over 90 days ensiled crop biomass in batch anaerobic digestion tests without further pre treatment. Lignin content of crop biomass was found to be the most significant explanatory variable for specific methane yields while the methane content and methane production rates were mainly affected by the content of nitrogen-free extracts and neutral detergent fibre, respectively. The accumulation of butyric acid and alcohols during the ensiling process had significant impact on specific methane yields and methane contents of crop silages. It is proposed that products of silage fermentation should be considered when evaluating crop silages for biogas production. PMID- 26836847 TI - Bioadsorption of Rare Earth Elements through Cell Surface Display of Lanthanide Binding Tags. AB - With the increasing demand for rare earth elements (REEs) in many emerging clean energy technologies, there is an urgent need for the development of new approaches for efficient REE extraction and recovery. As a step toward this goal, we genetically engineered the aerobic bacterium Caulobacter crescentus for REE adsorption through high-density cell surface display of lanthanide binding tags (LBTs) on its S-layer. The LBT-displayed strains exhibited enhanced adsorption of REEs compared to cells lacking LBT, high specificity for REEs, and an adsorption preference for REEs with small atomic radii. Adsorbed Tb(3+) could be effectively recovered using citrate, consistent with thermodynamic speciation calculations that predicted strong complexation of Tb(3+) by citrate. No reduction in Tb(3+) adsorption capacity was observed following citrate elution, enabling consecutive adsorption/desorption cycles. The LBT-displayed strain was effective for extracting REEs from the acid leachate of core samples collected at a prospective rare earth mine. Our collective results demonstrate a rapid, efficient, and reversible process for REE adsorption with potential industrial application for REE enrichment and separation. PMID- 26836848 TI - Anti-Toxoplasma Activity of Estragole and Thymol in Murine Models of Congenital and Noncongenital Toxoplasmosis. AB - Toxoplasmosis is caused by Toxoplasma gondii , an obligatory intracellular protozoan. Normally benign, T. gondii infections can cause devastating disease in immunosuppressed patients and through congenital infection of newborn babies. Few prophylactic and therapeutic drugs are available to treat these infections. The goal of the present study was to assess the anti-Toxoplasma effects in a congenital and noncongenital model of toxoplasmosis (using ME49 strain), besides assessing immunological changes, in vitro cytotoxicity, and in vivo acute toxicity of commercial estragole and thymol. The congenital experimental model was used with intermediate stages of maternal infection. The serum levels of immunoglobulin (Ig)M, IgG, interleukin (IL)-10, IL-12, and interferon-gamma (IFN gamma) were quantified from infected and treated C57Bl/6 mice. Estragole and thymol respectively exhibited low to moderate in vivo toxicity and cytotoxicity. Animals treated with estragole showed high IFN-gamma and strong type 1 helper T cell response. Both compounds were active against T. gondii ME49 strain. Furthermore, orally administered estragole in infected pregnant mice improved the weight of offspring compared with untreated controls. Subcutaneous administration of both compounds also increased the weight of mouse offspring born to infected mothers, compared with untreated controls. Estragole and thymol display important anti-Toxoplasma activity. Further studies are needed to elucidate the mechanism of action of these compounds. PMID- 26836850 TI - High-efficiency microchip laser with self-injection seeding. AB - In this paper, we use a small bandwidth 808 nm cw Ti:sapphire laser as a pump source to pump a picosecond microchip laser. Different focal length pump focus lenses have been tested to improve laser efficiency. A maximum slope efficiency of around 20% is obtained by a 30 mm focal length lens. The pump threshold is only 13 mW. In order to reduce the timing jitter, we explored the self-injection seeding method by adding a seeding cavity to the microchip laser. A reduction factor in the timing jitter of up to a factor of 23 relative to the unseeded laser is obtained. From the experiments, we also found that higher seeding pulse energy will help to reduce the jitter more. PMID- 26836849 TI - Liberation of Protein-Specific Glycosylation Information for Glycan Analysis by Exonuclease III-Aided Recycling Hybridization. AB - A strategy for information liberation of protein-specific glycosylation is designed via an exonuclease III-aided recycling "hybridization and cleavage" process with glycan and protein probes, which achieves homogeneous quantification of cell surface glycan. The protein probe contains matching and spacer DNA sequences and an aptamer specific to target protein. The glycan probe contains a complementary sequence modified with neighboring fluorescein and quencher, a spacer sequence, and a dibenzocyclooctyne-amine end to bind azide-tagged glycan. Upon sequential binding to their targets, the complementary sequences of two probes approach enough for their hybridization, which leads to the cleavage of hybridized glycan probe by exonuclease III and followed recycling "hybridization and cleavage" process of protein probe with other adjacent glycan probes to release the labeled fluorescein for obtaining the information on protein-specific glycosylation. This protocol has been used to in situ quantify EpCAM-specific sialic acid on MCF-7 cell surface and monitor its variation during drug treatment. This work demonstrates a powerful quantification tool for research of glycosylation. PMID- 26836851 TI - Scattering by a conductive half-screen between isorefractive media. AB - The scattering process of electromagnetic waves by a conductive half-plane, located between isorefractive media, is investigated. First, the conductive sheet at the interface of isorefractive media is considered. The reflection and transmission coefficients of the plane are evaluated. The diffracted fields by the half-plane are obtained with the aid of a relation between the diffracted and scattered geometrical optics waves. The resultant field expressions are numerically examined. PMID- 26836852 TI - Numerical analysis of lasing characteristics in highly bend-compensated large mode-area ytterbium-doped double-clad leakage channel fibers. AB - The bend-induced mode-area reduction and thermal effects are vital factors that affect the power scaling of fiber lasers. Recently, bend-compensated large-mode area double-clad modified hybrid leakage channel fiber (M-HLCF) has been reported with a mode area greater than 1000 MUm, while sustaining the single-mode behavior at 1064 nm for high-temperature environments. In this work, the lasing characteristics of a newly designed ytterbium-doped double-clad M-HLCF (YDMHLCF) have been numerically investigated for strongly pumped conditions. The doped region size is optimally found through simulations, equivalent to the size of core diameter ~38 MUm in order to achieve maximum conversion efficiency for the bent and straight cases. Numerical simulations further confirm that a 2 m long YDMHLCF exhibits slope efficiency of 78% and conversion efficiency of 79% for the straight case and also almost the same for the practical bending radius of 7.5 cm when pumped with a 975 nm laser source. PMID- 26836853 TI - Interference-type time lens based on temporal hologram in a loop configuration. AB - An alternative scheme is proposed for implementing a time lens based on the temporal hologram concept. Instead of using edge-pass filtering, this scheme achieves the keeping of only the time-lens (quadratic phase modulation) term of interest through the interference of two modulated component beams. In this scheme, an additional linear frequency component does not have to be added to the electronic drive signal to avoid the overlapping of the target frequency component and its conjugate of the modulated signal. Thus, the proposed hologram based time lens is not only able to relax the limitation of the bandwidth and sampling rate of the arbitrary waveform generator on the time-bandwidth product and resolution to some extent, but is also capable of processing shorter input pulse signals. These advantages make the proposed interference-type hologram time lens especially suitable for use in a loop configuration, where it can be reused when the signal pulse circulates in the loop. This promises significantly enhanced time-bandwidth product and resolution, and the temporal aperture size can be designed as large as desired theoretically. PMID- 26836854 TI - Adjustable hollow-cone output x-ray beam from an ellipsoidal monocapillary with a pinhole and a beam stop. AB - A combined shading system (CSS) consisting of a beam stop and a pinhole is proposed to be used between an ellipsoidal monocapillary (EM) and a conventional laboratory x-ray source to obtain an adjustable hollow-cone output beam for different experiments with no need for changing the EM. The CSS can change the incident x-ray beam on the EM by adjusting the position of the beam stop and the pinhole, with the corresponding change of the output beam of the EM. In this study, the adjustable hollow-cone output x-ray beam of an 80-mm-long EM with a CSS was studied in detail with a laboratory Cu x-ray generator with a focal spot diameter of 50 MUm. The adjustable range of the focal spot size of the EM was from 8.6 to 58.7 MUm. The adjustable range of the gain of the focal spot of the EM was from 0 to 1350. The beam divergence of the hollow-cone output beam of the EM ranged from 6 to 16.75 mrad. The illumination angle of the hollow-cone output beam of the EM ranged from 0 to 5.95 mrad. In addition, the potential application of the proposed adjusting method in testing the performance of the EM is briefly discussed. PMID- 26836855 TI - Real-time depth controllable integral imaging pickup and reconstruction method with a light field camera. AB - In this paper, we develop a real-time depth controllable integral imaging system. With a high-frame-rate camera and a focus controllable lens, light fields from various depth ranges can be captured. According to the image plane of the light field camera, the objects in virtual and real space are recorded simultaneously. The captured light field information is converted to the elemental image in real time without pseudoscopic problems. In addition, we derive characteristics and limitations of the light field camera as a 3D broadcasting capturing device with precise geometry optics. With further analysis, the implemented system provides more accurate light fields than existing devices without depth distortion. We adapt an f-number matching method at the capture and display stage to record a more exact light field and solve depth distortion, respectively. The algorithm allows the users to adjust the pixel mapping structure of the reconstructed 3D image in real time. The proposed method presents a possibility of a handheld real time 3D broadcasting system in a cheaper and more applicable way as compared to the previous methods. PMID- 26836856 TI - Fiber optic hydrogen sensor based on an etched Bragg grating coated with palladium. AB - A study of a sensor for hydrogen (H2) detection based on fiber Bragg gratings coated with palladium (Pd) with self-temperature compensation is presented. The cladding around the gratings was reduced down to 50 MUm diameter by a chemical etching process. One of the gratings was left uncoated, and the other was coated with 150 nm of Pd. It was observed that palladium hydride has unstable behavior in environments with high humidity level. A simple solution to overcome this problem based on a Teflon tape is presented. The sensing device studied was able to respond to H2 concentrations in the range 0%-1% v/v at room temperature and atmospheric pressure, achieving sensitivities larger than 20 pm/% v/v. Considering H2 concentrations in nitrogen up to 1%, the performance of the sensing head was characterized for different thicknesses of Pd coating ranging from 50 to 200 nm. PMID- 26836857 TI - Extinction efficiencies for metallic fibers in the infrared: erratum. AB - In this erratum, a correction of a previously computed extinction spectrum of a sample of silver fibers in the infrared [Appl. Opt.48, 5095 (2009)APOPAI0003 693510.1364/AO.48.005095] is reported. The spectrum was inaccurately computed through use of an approximation relating the E-field aligned values to those of the orientationally averaged extinction efficiency. This approximation is very close for spectral points in the vicinity of the primary resonance but not necessarily for those well away from this resonance. Here, the exact theory has been used to produce the spectra. PMID- 26836858 TI - Analysis of buried interfaces in multilayer mirrors using grazing incidence extreme ultraviolet reflectometry near resonance edges. AB - Accurate measurements of optical properties of multilayer (ML) mirrors and chemical compositions of interdiffusion layers are particularly challenging to date. In this work, an innovative and nondestructive experimental characterization method for multilayers is discussed. The method is based on extreme ultraviolet (EUV) reflectivity measurements performed on a wide grazing incidence angular range at an energy near the absorption resonance edge of low-Z elements in the ML components. This experimental method combined with the underlying physical phenomenon of abrupt changes of optical constants near EUV resonance edges enables us to characterize optical and structural properties of multilayers with high sensitivity. A major advantage of the method is to perform detailed quantitative analysis of buried interfaces of multilayer structures in a nondestructive and nonimaging setup. Coatings of Si/Mo multilayers on a Si substrate with period d=16.4 nm, number of bilayers N=25, and different capping structures are investigated. Stoichiometric compositions of Si-on-Mo and Mo-on-Si interface diffusion layers are derived. Effects of surface oxidation reactions and carbon contaminations on the optical constants of capping layers and the impact of neighboring atoms' interactions on optical responses of Si and Mo layers are discussed. PMID- 26836859 TI - Design of metallic nanoparticle gratings for filtering properties in the visible spectrum. AB - Plasmonic resonances in metallic nanoparticles are exploited to create efficient optical filtering functions. A finite element method is used to model metallic nanoparticle gratings. The accuracy of this method is shown by comparing numerical results with measurements on a two-dimensional grating of gold nanocylinders with an elliptic cross section. A parametric analysis is then performed in order to design efficient filters with polarization dependent properties together with high transparency over the visible range. The behavior of nanoparticle gratings is also modeled using the Maxwell-Garnett homogenization theory and analyzed by comparison with the diffraction of a single nanoparticle. The proposed structures are intended to be included in optical systems that could find innovative applications. PMID- 26836860 TI - Influence of size, proportion, and absorption coefficient of spherical scatterers on the degree of light polarization and the grain size of speckle pattern. AB - In this paper, we present the evolution of speckle pattern polarimetric parameters in response to controlled changes in scatterer sizes, proportions, and the absorption coefficient in media. The experimental study was performed on mixtures of polystyrene microspheres with dye in order to ensure biological medium-like properties. The speckle grain sizes and degrees of polarization for linear and circular light were monitored. We observed helicity flipping in the degree of circular polarization for small scatterer proportion around 25%. Furthermore, linear depolarization decreased slightly for media containing more small particles. Good agreement was shown with numerical results computed using a Monte Carlo simulation of polarized light taking into account our experimental configuration. Speckle grain size also evolves with the increase of small scatterers as well as the media absorption coefficient. Such variations of properties are encountered during fruit maturation, in tissues in precancerous stages, and any transformation that causes a modification in particle proportions and absorption coefficient in biological media. The computed parameters proved to be sensitive to these changes. PMID- 26836861 TI - Comparison of two methodologies for calibrating satellite instruments in the visible and near-infrared. AB - Traditionally, satellite instruments that measure Earth-reflected solar radiation in the visible and near infrared wavelength regions have been calibrated for radiance responsivity in a two-step method. In the first step, the relative spectral response (RSR) of the instrument is determined using a nearly monochromatic light source such as a lamp-illuminated monochromator. These sources do not typically fill the field of view of the instrument nor act as calibrated sources of light. Consequently, they only provide a relative (not absolute) spectral response for the instrument. In the second step, the instrument views a calibrated source of broadband light, such as a lamp illuminated integrating sphere. The RSR and the sphere's absolute spectral radiance are combined to determine the absolute spectral radiance responsivity (ASR) of the instrument. More recently, a full-aperture absolute calibration approach using widely tunable monochromatic lasers has been developed. Using these sources, the ASR of an instrument can be determined in a single step on a wavelength-by-wavelength basis. From these monochromatic ASRs, the responses of the instrument bands to broadband radiance sources can be calculated directly, eliminating the need for calibrated broadband light sources such as lamp illuminated integrating spheres. In this work, the traditional broadband source based calibration of the Suomi National Preparatory Project Visible Infrared Imaging Radiometer Suite sensor is compared with the laser-based calibration of the sensor. Finally, the impact of the new full-aperture laser-based calibration approach on the on-orbit performance of the sensor is considered. PMID- 26836862 TI - Traceable methods for vertical scale characterization of dynamic stroboscopic scanning white-light interferometer measurements. AB - Stroboscopic scanning white-light interferometry (SSWLI) can be used for 3D imaging of oscillating samples. It allows measurement of micrometer to millimeter size samples with nanometer vertical precision. Unlike coherent light source systems the SSWLI can measure unambiguously samples with vertical steps. Traceability of the vertical displacement measurement is important with SSWLI since the height measurement is not related to any specific monochromatic light wavelength. For static measurements SSWLI can be calibrated using, e.g., step height standards, but to characterize dynamic measurements traceable samples with accurate motion are needed due to error sources related to the frequency response of the SSWLI. In the presented method, SSWLI measurements are performed on dynamic transfer standards, which are characterized using a laser interferometer traceable to the SI meter. In this work dynamic SSWLI measurements at subkilohertz to 10.7 kHz frequencies with micrometer range displacement are characterized. The expanded uncertainty (k=2) was 9.6 nm for a measured displacement of 766 nm at 10.7 kHz. The methodology can be used up to the frequency limits of the SSWLI using suitable samples. PMID- 26836863 TI - Hyperbolic tangential function-based progressive addition lens design. AB - The diopter distribution is key to the successful design of a progressive addition lens. A hyperbolic tangential function is then introduced to describe well the desired diopter distribution on the lens. Simulation and fabrication show that the astigmia on the whole surface is very close to the addition, exhibiting superior performance than that of currently used high-order polynomials and cosine functions. Our investigations found that once the diopter distribution design is reasonable, both the direct and indirect methods of constructing a progressive addition lens can give consistent results. With this function we are able to effectively control the design of critical areas, the position, sizes of far-view and near-view zones, as well as the channel of the lens. This study would provide an efficient way to customize different progressive lenses not only for presbyopia, but also for anti-fatigue, office progressive usages, etc. PMID- 26836864 TI - Optical strain for monitoring of concrete failure mechanism with discontinuity. AB - Finite-element-based digital image correlation (FEM-DIC) is one of the most widely used noncontact techniques in the field of experimental mechanics for measurement of deformation/strain. In this paper, the FEM-DIC method is refined by introducing the concept of multilevel extended digital image correlation (X DIC), which also can capture deformation across discontinuity planes if they exist in images. Using regular and enhanced displacements at each node, strain tensors are estimated by applying the concept of smooth particle hydrodynamics (SPH). Numerical works are carried out to check the accuracy level of the developed algorithm by considering discrete discontinuity on the surface of a sample. Work is further extended to determine displacements and strains developed at the surface of several cubical concrete samples under uniaxial loading conditions. The tests are conducted until fractures are developed in the post failure region. Using the concept of cumulative effective strain, a parameter is identified, which can be used as a precursor in the object failure process. PMID- 26836865 TI - Improved synthetic-heterodyne Michelson interferometer vibrometer using phase and gain control feedback. AB - Synthetic-heterodyne demodulation is a useful technique for dynamic displacement and velocity measurement using interferometric sensors as it can provide an output signal which is immune to interferometric drift. With the advent of cost effective, high-speed real-time signal processing systems and software, processing of the complex signals encountered in interferometry has become more feasible. In conventional synthetic-heterodyne demodulation schemes, to obtain the dynamic displacement or vibration of the object under test requires knowledge of the interferometer visibility and also the argument of two Bessel functions. In this paper, a new synthetic-heterodyne demodulation method is described leading to an expression for the dynamic displacement and velocity of the object under test that is significantly less sensitive to the received optical power. In addition, the application of two independent phase and gain feedback loops is used to compensate for the nonideal gain and phase response of the anti-aliasing filter required for the signal acquisition of the received wideband interferometer signal. The efficacy of the improved system is demonstrated by measuring the displacement sensitivity frequency response and linearity of a Piezoelectric Mirror-Shifter (PMS) over a range of 200 Hz-9 kHz. In addition, the system is used to measure the response of the PMS to triangular and impulse type stimuli. The experimental results show excellent agreement with measurements taken using two independent industry standard calibration methods. PMID- 26836866 TI - Optical detection of glucose concentration in samples with scattering particles. AB - An optical-based method is proposed for measuring the glucose concentration of samples containing scattering particles. In the proposed approach, a Stokes Mueller reflection-based polarimetry technique is used to solve the Mueller matrices of a turbid glucose sample with circular birefringence and depolarization properties given six incident lights with different polarization states. Using an error function defined as the difference between the simulated output Stokes vectors and the experimental ones, a genetic algorithm is used to inversely derive the optical rotation and depolarization parameters of the experimental sample corresponding to the glucose concentration and scattering depolarization effect, respectively. The validity of the proposed method is demonstrated using glucose samples containing 0.02 ml and 0.04 ml lipofundin, respectively. PMID- 26836867 TI - Reconstruction of laser-induced cavitation bubble dynamics based on a Fresnel propagation approach. AB - A single laser-induced cavitation bubble in transparent liquids has been studied through a variety of experimental techniques. High-speed video with varying frame rate up to 20*10(7) fps is the most suitable to study nonsymmetric bubbles. However, it is still expensive for most researchers and more affordable (lower) frame rates are not enough to completely reproduce bubble dynamics. This paper focuses on combining the spatial transmittance modulation (STM) technique, a single shot cavitation bubble and a very simple and inexpensive experimental technique, based on Fresnel approximation propagation theory, to reproduce a laser-induced cavitation spatial dynamics. Our results show that the proposed methodology reproduces a laser-induced cavitation event much more accurately than 75,000 fps video recording. In conclusion, we propose a novel methodology to reproduce laser-induced cavitation events that combine the STM technique with Fresnel propagation approximation theory that properly reproduces a laser-induced cavitation event including a very precise identification of the first, second, and third collapses of the cavitation bubble. PMID- 26836868 TI - Transient gain analysis of gain-switched semiconductor lasers during pulse lasing. AB - We analyzed the transient gain properties of three gain-switched semiconductor lasers with different materials and cavity structures during pulse lasing. All the semiconductor lasers were pumped with impulse optical pumping, and all the generated gain-switched output pulses were well described by exponential functions in their rise parts, wherein the transient gains were derived according to the rate-equation theoretical model. In spite of the different laser structures and materials, the results consistently demonstrated that a higher transient gain produces shorter output pulses, indicating the dominant role of higher transient gain in the generation of even shorter gain-switched pulses with semiconductor lasers. PMID- 26836869 TI - Fully automated, high speed, tomographic phase object reconstruction using the transport of intensity equation in transmission and reflection configurations. AB - While traditional transport of intensity equation (TIE) based phase retrieval of a phase object is performed through axial translation of the CCD, in this work a tunable lens TIE is employed in both transmission and reflection configurations. These configurations are extended to a 360 degrees tomographic 3D reconstruction through multiple illuminations from different angles by a custom fabricated rotating assembly of the phase object. Synchronization circuitry is developed to control the CCD camera and the Arduino board, which in its turn controls the tunable lens and the stepper motor to automate the tomographic reconstruction process. Finally, a MATLAB based user friendly graphical user interface is developed to control the whole system and perform tomographic reconstruction using both multiplicative and inverse radon based techniques. PMID- 26836870 TI - Calibration of windowless photodiode for extreme ultraviolet pulse energy measurement. AB - For energy measurement of extreme ultraviolet pulses, no universal commercially available device is available. Therefore, a co-axial setup of a vacuum photodiode was developed and tested. First its unsuccessful calibration at the National Institute of Standards and Technology (USA) is mentioned. Then our own single wavelength (46.9 nm) calibration procedure is described in detail. It is based on tabulated photoemission efficiency and on measured (1) anode collection efficiency, (2) attenuation of Al filters, and (3) attenuation of measuring cables. Some other relevant attenuating factors are also taken into account. PMID- 26836871 TI - Modeling the whispering gallery microresonator-based optical modulator. AB - We present a theoretical analysis and numerical simulations of an electro-optic double resonant modulator based on interaction of fundamental whispering gallery modes with a radio frequency field in a dielectric microdisk made from electro optical material. Models of the modulator in two dimensions and three dimensions are developed and compared. Both optical and RF fields are simulated using the finite element method. The magnitude of the effect in such a system may be maximized with an optimum configuration of a microstrip resonator used for radio frequency coupling. PMID- 26836872 TI - Precision enhancement method for multiplexing image detector-based sun sensor with varying and coded apertures. AB - The multiplexing image detector-based sun sensor has an extremely high accuracy and a large field of view (FOV) due to its large focal length, hundreds of apertures, and tens of sub-FOVs. Because of the optical interference effect, the diffraction spots of the sun on the image detector will be greatly influenced by the incident sun angles and the sizes of apertures, which affect the extraction precision of the sun spot centroid to a great extent. In this work, according to the Huygens-Fresnel diffraction integral formula and the aperture numerical simulations at different incident sun angles, we present a novel proposal for the mask with varying aperture sizes in different sub-FOVs. We encoded the aperture arrays with distance information for sub-FOV distinction. The laboratory test results indicated that, compared with the same aperture pattern design, the extraction precision of the sun spots with the varying apertures pattern design was better in a larger angle and more stable in the whole FOV, and the precision of the sun sensor could be improved to 1.32" (1sigma) from 4.52" (1sigma) at a 50 degrees incident sun angle. PMID- 26836873 TI - Diffractively corrected counter-rotating Risley prisms. AB - Using the vector refraction equation and the vector diffraction equation, we obtain the expressions of the direction cosines of the refractive rays for the two wedge prisms, and the direction cosines of the diffractive rays for two wedge grisms, in which diffractive gratings were etched into the prism faces to correct the chromatic aberrations. A mathematical model between the two vector equations is proposed to compare the difference angle chromatic aberrations when the Risley prisms/grisms are rotating at different angles. We conclude that the use of diffractively corrected prisms offers a new method to correct chromatic aberrations in Risley prisms. PMID- 26836874 TI - Fabry-Perot based strain insensitive photonic crystal fiber modal interferometer for inline sensing of refractive index and temperature. AB - We report a highly stable, compact, strain insensitive inline microcavity-based solid-core photonic crystal fiber (SCPCF) modal interferometer for the determination of the refractive index (RI) of an analyte and its temperature. The interferometer is fabricated by splicing one end of SCPCF with single-mode fiber (SMF) and the other end with hollow-core PCF. This is followed by cleaving the part of the solid glass portion possibly present after the microcavity. The formation of the cavities at the end faces of the SCPCF results in reduction of the period of the interference pattern that helps in achieving distinctiveness in the measurement. Three sensor heads have been fabricated, and each has a different length of the collapsed region formed by splicing SMF with SCPCF. The response of the sensors is found to be sensitive to the length of this collapsed region between SMF and SCPCF with a sensitivity of 53 nm/RI unit (RIU) and resolution of 1.8*10(-4) RIU. The temperature response of the sensor is found to be linear, having a temperature sensitivity of 12 pm/ degrees C. In addition to these findings, the effect of strain on the proposed structure is analyzed in both wavelength and intensity interrogation. PMID- 26836875 TI - Propagation characteristics of continuously tuning distorted Airy-like beams. AB - We investigate theoretically and observe experimentally a continuously tuning distorted Airy-like beam, which is generated by introducing a controllable rotation angle into the phase patterns. The beam wavefront can be tuned flexibly by using the introduced angle. The main lobes of beams can be controlled readily to propagate along specified parabolic trajectories. The relevant optical behaviors are discussed and demonstrated in detail. The experimental results are in good agreement with the theoretical analysis. The intriguing characteristics of the continuously tuning Airy-like beams could provide more degrees of freedom in cell and atom manipulation. PMID- 26836876 TI - Frequency stabilization of an optically pumped far-infrared laser to the harmonic of a microwave synthesizer. AB - Measurements of the frequency stability of a far-infrared molecular laser have been made by mixing the harmonic of an ultrastable microwave source with a portion of the laser output signal in a terahertz (THz) Schottky diode balanced mixer. A 3 GHz difference-frequency signal was used in a frequency discriminator circuit to lock the laser to the microwave source. Comparisons of the short- and long-term laser frequency stability under free-running and locked conditions show a significant improvement with locking. Short-term frequency jitter was reduced by an order of magnitude, from approximately 40 to 4 kHz, and long-term drift was reduced by more than three orders of magnitude, from approximately 250 kHz to 80 Hz. The results, enabled by the efficient Schottky diode balanced mixer downconverter, demonstrate that ultrastable microwave-based frequency stabilization of THz optically pumped lasers (OPLs) will now be possible at frequencies extending well above 4.0 THz. PMID- 26836877 TI - Fluoride coatings for vacuum ultraviolet reflection filters. AB - LaF3/MgF2 reflection filters with a high spectral-discrimination capacity of the atomic-oxygen lines at 130.4 and 135.6 nm, which were employed in vacuum ultraviolet imagers, were prepared by molybdenum-boat thermal evaporation. The optical properties of reflection filters were characterized by a high-precision vacuum ultraviolet spectrophotometer. The vulnerability of the filter's microstructures to environmental contamination and the recovery of the optical properties of the stored filter samples with ultraviolet ozone cleaning were experimentally demonstrated. For reflection filters with the optimized nonquarter wave multilayer structures, the reflectance ratios R135.6 nm/R130.4 nm of 92.7 and 20.6 were achieved for 7 degrees and 45 degrees angles of incidence, respectively. On the contrary, R135.6 nm/R130.4 nm ratio of 12.4 was obtained for a reflection filter with a standard pi-stack multilayer structure with H/L=1/4 at 7 degrees AOI. PMID- 26836878 TI - Intrafilm separation of solgel film under nanosecond irradiation. AB - We have observed large-scale intrafilm separation after the irradiation of solgel film with a single Nd:YAG pulse (1064 nm, 12 ns) in air. The irradiated but undamaged surface or the surface after intrafilm separation is densified. These damage features are distinctly different from the scalding surface of the electron beam evaporation coating or the ripple structures on the rear surface of fused silica, which indicates the extreme pressure gradients at the free surface film interface. The submicrometer size melted cavity in the center of damage site is related with the nanoscale absorber. A phenomenological description that combines the defect-induced incubation phase and laser-supported surface breakdown wave is used to explain the damage process. PMID- 26836879 TI - Evolution properties of partially coherent flat-topped vortex hollow beam in oceanic turbulence. AB - Employing the theory of coherence, the partially coherent flat-topped vortex hollow beam is first introduced. The analytical propagation equation for a partially coherent flat-topped vortex hollow beam in oceanic turbulence is derived by using the extended Huygens-Fresnel diffraction integral and the spectrum of oceanic turbulence. The influences of coherence length, beam order N, the topological charge M, and the parameters of oceanic turbulence on evolution properties of partially coherent flat-topped vortex hollow beams propagating in oceanic turbulence are obtained by using the numerical examples. PMID- 26836880 TI - Dual-loss-modulated Q-switched mode-locked laser intracavity pumped temperature tuned subnanosecond KTiOPO4 optical parametric oscillator. AB - Using an acousto-optic modulator (AOM) and Cr4+:YAG as the dual-loss modulation, an intracavity KTiOPO4 optical parametric oscillator (OPO) pumped by a simultaneously Q-switched and mode-locked (QML) YVO4/Nd:YVO4 laser was realized. The shortest mode-locking pulse duration of the signal wave at 1573 nm was directly measured as 450 ps at an AOM frequency of 2 kHz and a diode pump power of 10.5 W, corresponding to a peak power of 35.5 kW. The temperature tuning of the output signal wavelength was realized in the range from 1571.99 to 1572.61 nm with a blueshift ratio of 0.027 nm/ degrees C. A set of coupled rate equations for the dual-loss-modulated QML laser pumping intracavity OPO was built for the first time to our knowledge. The numerical solutions were fitted with the experimental results. PMID- 26836881 TI - Wavelength-dependent femtosecond pulse amplification in wideband tapered waveguide quantum well semiconductor optical amplifiers. AB - In this paper, we study the wavelength-dependent amplification in three different wideband quantum well semiconductor optical amplifiers (QWAs) having conventional, exponentially tapered, and linearly tapered active region waveguide structures. A new theoretical model for tapered-waveguide QWAs considering the effect of lateral carrier density distribution and the strain effect in the quantum well is established based on a quantum well transmission line modeling method. The temporal and spectral characteristics of amplified femtosecond pulse are analyzed for each structure. It was found that, for the amplification of a single femtosecond pulse, the tapered-waveguide QWA provides higher saturation gain, and the output spectra of the amplified pulse in all three structures exhibit an apparent redshift and bandwidth narrowing due to the reduction of carrier density; however, the output spectrum in the tapered-waveguide amplifier is less distorted and exhibits smaller bandwidth narrowing. For the simultaneous amplification of two femtosecond pulses with different central frequencies, in all the three structures, two peaks appear in the output spectra while the peak at the frequency closer to the peak frequency of the QWA gain spectrum receives higher amplification due to the frequency (wavelength) dependence of the QWA gain. At a low peak power level of the input pulse, the bandwidth of each window in the tapered structure is larger than that of the conventional waveguide structure, which aggravates the spectrum alias in the amplification of femtosecond pulses with different central frequencies. As the peak powers of the two pulses increase, the spectrum alias in the conventional waveguide becomes more serious while there are small changes in the tapered structures. Also, we have found that in the amplification of a femtosecond pulse train, the linear tapered QWAs exhibit the fastest gain recovery as compared with the conventional and exponentially tapered QWAs. PMID- 26836882 TI - Experimental investigation on the infrared refraction and extinction properties of rock dust in tunneling face of coal mine. AB - Comprehensive experimental research on the fundamental optical properties of dust pollution in a coal mine is presented. Rock dust generated in a tunneling roadway was sampled and the spectral complex refractive index within an infrared range of 2.5-25 MUm was obtained by Fourier transform infrared spectroscopy measurement and Kramers-Kronig relation. Experimental results were validated to be consistent with equivalent optical constants simulated by effective medium theory based on component analysis of x-ray fluorescence, which illustrates that the top three mineral components are SiO2 (62.06%), Al2O3 (21.26%), and Fe2O3 (4.27%). The complex refractive index and the spatial distribution tested by a filter dust and particle size analyzer were involved in the simulation of extinction properties of rock dust along the tunneling roadway solved by the discrete ordinates method and Mie scattering model. The compared results illustrate that transmission is obviously enhanced with the increase of height from the floor but weakened with increasing horizontal distance from the air duct. PMID- 26836884 TI - Source spectrum shaping method for low-coherence interferometry. AB - Low-coherence interferometry (LCI) suffers mainly from low signal-to-noise (S/N) ratio. By using the source spectrum shaping method (SSSM), the authors can enhance the visibility of the zero-order fringe (V) and S/N ratio in LCI. The presented approach was analyzed numerically for a set of theoretical Gaussian light sources, with different central wavelengths and different spectrum widths. The results have shown a significant improvement of the visibility V. Additionally, a set of commercially available light emitting diodes was analyzed to find the best possible setup. Results of numerical calculations were verified experimentally in an SSSM low coherence Twyman-Green interferometric setup equipped with three light sources. PMID- 26836883 TI - Theoretical considerations on aperiodic sinusoidal fringes in comparison to phase shifted sinusoidal fringes for high-speed three-dimensional shape measurement. AB - The demand for optically reconstructing the three-dimensional (3D) surface shape of moving objects or deformation processes makes the development of high-speed projectors necessary. Our 3D sensor containing an array projector can achieve frame rates of several tens of kilohertz and is based on the projection of aperiodic sinusoidal fringes. This approach is compared with phase-shifting fringe projection as probably the most widely used technique. Theoretical considerations as well as extensive simulations are conducted to derive criteria for the design of optimal sequences of aperiodic sinusoidal fringes and to compare the number of patterns of both approaches necessary for comparable accuracies. PMID- 26836885 TI - Human skin detection in the visible and near infrared. AB - Skin detection is a well-studied area in color imagery and is useful in a number of scenarios to include search and rescue and computer vision. Most approaches focus on color imagery due to cost and availability. Many of the visible-based approaches do well at detecting skin (above 90%) but they tend to have relatively high false-alarm rates (8%-15%). This article presents a novel feature space for skin detection in visible and near infrared portions of the electromagnetic spectrum. The features are derived from known spectral absorption of skin constituents to include hemoglobin, melanin, and water as well as scattering properties of the dermis. Fitting a Gaussian mixture to skin and background distributions and using a likelihood ratio test detector, the features presented here show dominating performance when comparing receiver-operating characteristic curves (ROCs) and statistically significant improvement when comparing equal error rates and area under the ROC (AUC). A detection/false-alarm probability of 98.6%/1.1% is achieved for the averaged equal error rate (EER). EER values for the proposed feature space show a 5.6%-11.2% increase in detection probability with a 6.0%-11.6% decrease in false-alarm probability compared to well performing color-based features. The AUC shows a 0.034-0.173 increase in total area under the curve compared to well performing color-based features. PMID- 26836886 TI - Two early career pointers: editorial. AB - Editor-in-Chief Ron Driggers shares advice for early career professionals about cultivating a publication record and a funded research record. PMID- 26836887 TI - Recent updates on GPCR biased agonism. AB - G protein-coupled receptors (GPCRs) are the most important targets for drug discovery and not surprisingly ~40% of all drugs currently in the market act on these receptors. Currently, one of the most active areas in GPCRs signaling is biased agonism, a phenomenon that occurs when a given ligand is able to preferentially activate one (or some) of the possible signaling pathways. In this review, we highlight the most recent findings about biased agonism, including an extension of this concept to intracellular signaling, allosterism, strategies for assessment and interpretation, and perspectives of therapeutic applications for biased agonists. PMID- 26836888 TI - Supplementation with coenzyme Q10 reduces plasma lipoprotein(a) concentrations but not other lipid indices: A systematic review and meta-analysis. AB - Plasma lipoprotein(a) [Lp(a)] elevations are associated with increased cardiovascular risk. Coenzyme Q10 (CoQ10) is a member of the mitochondrial respiratory chain with a prominent role as a potent gene regulator. The Lp(a) lowering efficacy of CoQ10 has been investigated in different clinical settings with contrasting results. A systematic literature search in Medline, SCOPUS, Web of Science and Google Scholar databases was conducted to identify controlled trials investigating the efficacy of CoQ10 supplementation on plasma Lp(a) levels. Inverse variance-weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes in Lp(a) levels using a random effects model. Random-effects meta-regression was performed to assess the effect of putative confounders on plasma Lp(a) levels. Seven randomized controlled trials with a total of 409 subjects (206 in the CoQ10 arm and 203 in the control arm) met the eligibility criteria. Overall, CoQ10 supplementation was paralleled by a slight but significant reduction of plasma Lp(a) levels (WMD: -3.54 mg/dL, 95% CI: -5.50, -1.58; p<0.001), this effect being more robust in those trials with higher baseline Lp(a) levels (slope: -0.44; 95% CI: -0.80, -0.08; p=0.018). Reduction of plasma Lp(a) levels was consistent across different CoQ10 doses, with an inverse association between administered CoQ10 dose and Lp(a) lowering (slope: 0.04; 95% CI: 0.01, 0.07; p=0.004). Neither total cholesterol and cholesterol subfractions, nor triglyceride levels were affected by CoQ10 supplementation. In conclusion, CoQ10 supplementation, in the tested range of doses, reduces plasma Lp(a) concentrations, particularly in patients with Lp(a)>= 30 mg/dL. Other lipid indices were not altered by CoQ10 supplementation. PMID- 26836890 TI - Contribution of the Mitochondria to Locomotor Muscle Dysfunction in Patients With COPD. AB - COPD is a significant public health challenge, notably set to become the third leading cause of death and fifth leading cause of chronic disability worldwide by the next decade. Skeletal muscle impairment is now recognized as a disabling, extrapulmonary consequence of COPD that is associated with reduced quality of life and premature mortality. Because COPD typically manifests in older individuals, these clinical features may overlie normal age-associated declines in muscle function and performance. Although physical inactivity, oxidative stress, inflammation, hypoxia, malnutrition, and medications all likely contribute to this comorbidity, a better understanding of the underlying mechanism is needed to develop effective therapies. Mitochondrial alterations have been described; these alterations include reductions in density and oxidative enzyme activity, increased mitochondrial reactive oxygen species production, and induction of muscle proteolysis including autophagy. This review focuses on the perspective that mitochondrial alterations contribute to impaired locomotor muscle performance in patients with COPD by reducing oxidative capacity and thus endurance, as well as by triggering proteolysis and thus contributing to atrophy and weakness. We discuss how the potential underlying mechanisms converge on mitochondria by targeting the peroxisome proliferator-activated receptor gamma coactivator-1alpha signaling pathway (thereby reducing mitochondrial biogenesis and muscle oxidative capacity and potentially increasing fiber atrophy) and how taking advantage of normal muscle plasticity and mitochondrial biogenesis may reverse this pathophysiology. We propose recent therapeutic strategies aimed at increasing peroxisome proliferator-activated receptor gamma-coactivator-1alpha levels, such as endurance training and exercise mimetic drugs, with the strong rationale for increasing mitochondrial biogenesis and function and thus improving the muscle phenotype in COPD. PMID- 26836889 TI - Relationship of Bisphosphonate Therapy and Atrial Fibrillation/Flutter: Outcomes of Sleep Disorders in Older Men (MrOS Sleep) Study. AB - BACKGROUND: Prior studies suggested an association between bisphosphonates and atrial fibrillation/flutter (AF) in women. This relationship in men, including those with sleep-disordered breathing (SDB), remains unclear. This study evaluated the relationship between bisphosphonate use and prevalent (nocturnal) and incident (clinically relevant) AF in a population of community-dwelling older men. METHODS: A total of 2,911 male participants (mean age, 76 years) of the prospective observational Osteoporotic Fractures in Men Study sleep cohort with overnight in-home polysomnography (PSG) constituted the analytic cohort. Nocturnal AF from ECGs during PSG and incident AF events were centrally adjudicated. The association of bisphosphonate use and AF was examined using multivariable-adjusted logistic regression for prevalent AF and Cox proportional hazards regression for incident AF. RESULTS: A total of 123 (4.2%) men were current bisphosphonate users. Prevalent nocturnal AF was present in 138 participants (4.6%). After multivariable adjustment, there was a significant association between current bisphosphonate use and prevalent AF (OR, 2.33; 95% CI, 1.13-4.79). In the subset of men with moderate to severe SDB, this association was even more pronounced (OR, 3.22; 95% CI, 1.29-8.03). However, the multivariable-adjusted relationship between bisphosphonate use and incident AF did not reach statistical significance (adjusted hazard ratio, 1.53; 95% CI, 0.96 2.45). CONCLUSIONS: These results support an association between bisphosphonate use and prevalent nocturnal AF in community-dwelling older men. The data further suggest that those with moderate to severe SDB may be a particularly vulnerable group susceptible to bisphosphonate-related AF. Similar associations were not seen for bisphosphonate use and clinically relevant incident AF. PMID- 26836891 TI - Update on Exhaled Nitric Oxide in Clinical Practice. AB - Asthma is characterized by chronic airway inflammation. Fractional exhaled nitric oxide (Feno) has emerged as a marker of T-helper cell type 2-mediated allergic airway inflammation. Recent studies suggest a role for Feno testing as a point-of care tool in the management of patients with asthma. This Topics in Practice Management article reviews current coverage and reimbursement issues related to Feno testing and provides an overview of pertinent recent studies. PMID- 26836892 TI - Comorbidome, Pattern, and Impact of Asthma-COPD Overlap Syndrome in Real Life. AB - BACKGROUND: Asthma-COPD overlap syndrome (ACOS) has been described and acknowledged as a distinct clinical entity; however, its characteristics in daily clinical practice are largely unknown. The aim of this study was to identify the prevalence of ACOS in the real-life population, its pattern of comorbidities, and its impact on hospitalization risk. METHODS: Data for this retrospective cohort study were extracted from the Majorca Real-Life Investigation in COPD and Asthma cohort, including primary care, hospitalization, and pharmacy data from the Balearic Islands, Spain. Patients who had received a physician-confirmed diagnosis of both asthma and COPD were identified as having ACOS and compared with a COPD-only population. In subanalyses, more stringent diagnostic criteria (Global Initiative for Asthma-Global Initiative for Chronic Obstructive Lung Disease) were applied. The pattern and impact of comorbidities on all-cause hospitalization were compared by multivariate logistic regression. RESULTS: In total, 5,093 patients with ACOS (prevalence, 5.55 per 1,000 inhabitants) were compared with 22,778 patients with COPD (30.40 per 1,000 inhabitants). Patients with ACOS were more frequently female (53.4%) than were patients with COPD (30.8%), younger (ACOS, 64.0 years; COPD, 65.8 years), and differed by nonsmoking status (ACOS, 41.4%; COPD, 22.1%) (all, P < .001). In adjusted analyses, allergic rhinitis (OR, 1.81; 95% CI, 1.63-2.00), anxiety (OR, 1.18; 95% CI, 1.10-1.27), gastroesophageal reflux disease (OR, 1.18; 95% CI, 1.04-1.33), and osteoporosis (OR, 1.14; 95% CI, 1.04-1.26) were more frequent in ACOS than COPD. In contrast, chronic kidney disease (OR, 0.79; 95% CI, 0.66-0.95) and ischemic heart disease (OR, 0.88; 95% CI, 0.79-0.98) were less frequent. In patients with ACOS, cardiovascular diseases showed the strongest association with hospitalization. CONCLUSIONS: ACOS is prevalent in the general population, and it affects to a large extent females with less smoking exposure compared with patients with COPD only. Cardiovascular comorbidities in particular contribute most to overall hospitalization risk of patients with ACOS. PMID- 26836893 TI - Vessels of the Central Airways: A Bronchoscopic Perspective. AB - Blood supply of the tracheobronchial tree is derived from a dual system involving pulmonary and bronchial circulation. Various primary and secondary abnormalities of central airway vasculature can present with patterns that are distinct during bronchoscopy. These patterns maybe visualized during bronchoscopic evaluation of a patient with hemoptysis or as an incidental finding during an airway examination for other indications. Thorough knowledge of airway vasculature abnormalities and recognition of possible underlying pathophysiology is vital for the bronchoscopist. This review is a comprehensive description of vascular anatomy of the airway and the different vascular abnormalities that can be encountered during bronchoscopy. PMID- 26836894 TI - Ionized Calcium in the ICU: Should It Be Measured and Corrected? AB - Serum ionized calcium (iCa) is often measured in patients admitted to ICUs, and at least half of these patients will have values outside the reference range during their ICU stay. The vast majority of these patients do not have an underlying disease of calcium homeostasis. This Contemporary Review discusses the rationale for measurement of iCa and whether available data support its measurement and correction. It is determined that while measurement of serum iCa is commonplace and attempted correction is popular, available evidence and logical analysis do not wholly support these practices. Abnormal values of iCa are likely a marker of disease severity in critical illness and most often normalize spontaneously with resolution of the primary disease process. Alternatively, low iCa levels in critical illness may be protective and attempted correction of low levels may be harmful. Dramatic curtailment of iCa measurement and calcium administration in several studies was not associated with worsening outcomes. The absence of high-quality data to guide practice allows for a spectrum of approaches to the measurement and treatment of iCa, but these approaches should be guided by basic principles of rational clinical decision making. Widespread, protocolized measurement and administration with the simple goal of normalizing values in the name of "euboxia" should be discouraged. PMID- 26836896 TI - Lung Ultrasound for Early Diagnosis of Ventilator-Associated Pneumonia. AB - BACKGROUND: Lung ultrasound (LUS) has been successfully applied for monitoring aeration in ventilator-associated pneumonia (VAP) and to diagnose and monitor community-acquired pneumonia. However, no scientific evidence is yet available on whether LUS reliably improves the diagnosis of VAP. METHODS: In a multicenter prospective study of 99 patients with suspected VAP, we investigated the diagnostic performance of LUS findings of infection, subpleural consolidation, lobar consolidation, and dynamic arborescent/linear air bronchogram. We also evaluated the combination of LUS with direct microbiologic examination of endotracheal aspirates (EA). Scores for LUS findings and EA were analyzed in two ways. First, the clinical-LUS score (ventilator-associated pneumonia lung ultrasound score [VPLUS]) was calculated as follows: >= 2 areas with subpleural consolidations, 1 point; >= 1 area with dynamic arborescent/linear air bronchogram, 2 points; and purulent EA, 1 point. Second, the VPLUS-direct gram stain examination (EAgram) was scored as follows: >= 2 areas with subpleural consolidations, 1 point; >= 1 area with dynamic arborescent/linear air bronchogram, 2 points; purulent EA, 1 point; and positive direct gram stain EA examination, 2 points. RESULTS: For the diagnosis of VAP, subpleural consolidation and dynamic arborescent/linear air bronchogram had a positive predictive value of 86% with a positive likelihood ratio of 2.8. Two dynamic linear/arborescent air bronchograms produced a positive predictive value of 94% with a positive likelihood ratio of 7.1. The area under the curve for VPLUS EAgram and VPLUS were 0.832 and 0.743, respectively. VPLUS-EAgram >= 3 had 77% (58-90) specificity and 78% (65-88) sensitivity; VPLUS >= 2 had 69% (50-84) specificity and 71% (58-81) sensitivity. CONCLUSIONS: By detecting ultrasound features of infection, LUS was a reliable tool for early VAP diagnosis at the bedside. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02244723; URL: www.clinicaltrials.gov. PMID- 26836897 TI - Efficacy of EGFR Tyrosine Kinase Inhibitors in the Adjuvant Treatment for Operable Non-small Cell Lung Cancer by a Meta-Analysis. AB - BACKGROUND: The role of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the adjuvant treatment of non-small cell lung cancer (NSCLC) has not been well-established. Our meta-analysis aimed to determine whether the administration of EGFR-TKIs could improve the outcomes of patients with NSCLC undergoing complete resection. METHODS: We comprehensively searched databases and extracted data from eligible studies. Disease-free survival (DFS) and overall survival (OS) with hazard ratios (HRs) as well as disease relapse with odds ratios (OR) were calculated using random and/or fixed-effects models. Meta regression analysis and test for interaction between subgroups were also carried out. RESULTS: A total of 1,960 patients in five studies were included. Adjuvant EGFR-TKI treatment was associated with a significant benefit on DFS (HR, 0.63; 95% CI, 0.41-0.99), corresponding to an absolute benefit of 3.1% at 3 years, yet with significant heterogeneity (I(2) = 83.4%, P < .001). The survival benefit was superior (Pinteraction = .03) in studies with more than an 18-month median treatment duration. EGFR mutation rate was also identified as a source of heterogeneity (P = .017). In the population with EGFR mutations, HR for DFS was 0.48 (95% CI, 0.36-0.65), corresponding to an absolute benefit of 9.5% at 3 years, with a reduced risk of distant metastasis (OR, 0.71; 95% CI, 0.56-0.92). Adjuvant EGFR-TKI treatment resulted in a marginally statistically significant benefit on OS (HR, 0.72; 95% CI, 0.49-1.06). The rate of overall grade 3 or greater adverse events was 42.3% (95% CI, 39.1-45.6). CONCLUSIONS: Adjuvant EGFR TKI treatment may enhance disease-free survival and reduce the risk of distant metastasis in patients with EGFR-mutant NSCLC undergoing complete resection. PMID- 26836895 TI - Age-Related Differences in Health-Related Quality of Life in COPD: An Analysis of the COPDGene and SPIROMICS Cohorts. AB - OBJECTIVE: Younger persons with COPD report worse health-related quality of life (HRQL) than do older individuals. The factors explaining these differences remain unclear. The objective of this article was to explore factors associated with age related differences in HRQL in COPD. METHODS: Cross-sectional analysis of participants with COPD, any Global Initiative for Chronic Obstructive Lung Disease grade of airflow limitation, and >= 50 years old in two cohorts: the Genetic Epidemiology of COPD (COPDGene) study and the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). We compared St. George's Respiratory Questionnaire (SGRQ) scores by age group: middle-aged (age, 50-64) vs older (age, 65-80) adults. We used multivariate linear modeling to test associations of age with HRQL, adjusting for demographic and clinical characteristics and comorbidities. RESULTS: Among 4,097 participants in the COPDGene study (2,170 middle-aged and 1,927 older adults) SGRQ total scores were higher (worse) among middle-aged (mean difference, -4.2 points; 95% CI, -5.7 to 2.6; P < .001) than older adults. Age had a statistically significant interaction with dyspnea (P < .001). Greater dyspnea severity (modified Medical Research Council >= 2, compared with 0-1) had a stronger association with SGRQ score among middle-aged (beta, 24.6; 95% CI, 23.2-25.9) than older-adult (beta, 21.0; 95% CI, 19.6-22.3) participants. In analyses using SGRQ as outcome in 1,522 participants in SPIROMICS (598 middle-aged and 924 older adults), we found similar associations, confirming that for the same severity of dyspnea there is a stronger association with HRQL among younger individuals. CONCLUSIONS: Age related differences in HRQL may be explained by a higher impact of dyspnea among younger subjects with COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764 and No.: NCT01969344; URL: www.clinicaltrials.gov. PMID- 26836898 TI - Reduced Antiviral Interferon Production in Poorly Controlled Asthma Is Associated With Neutrophilic Inflammation and High-Dose Inhaled Corticosteroids. AB - BACKGROUND: Asthma is a heterogeneous chronic inflammatory disease in which host defense against respiratory viruses such as human rhinovirus (HRV) may be abnormal. This is a matter of some controversy, with some investigators reporting reduced type I interferon (IFN) synthesis and others suggesting that type I IFN synthesis is relatively normal in asthma. OBJECTIVE: The objective of this study was to examine the responsiveness of circulating mononuclear cells to HRV in a large cohort of participants with poorly controlled asthma and determine whether IFN-alpha and IFN-beta synthesis varies across different inflammatory phenotypes. METHODS: Eligible adults with asthma (n = 86) underwent clinical assessment, sputum induction, and blood sampling. Asthma inflammatory subtypes were defined by sputum cell count, and supernatant assessed for IL-1beta. Peripheral blood mononuclear cells (PBMCs) were exposed to HRV serotype 1b, and IFN-alpha and IFN beta release was measured by enzyme-linked immunosorbent assay. RESULTS: Participants (mean age, 59 years; atopy, 76%) had suboptimal asthma control (mean asthma control questionnaire 6, 1.7). In those with neutrophilic asthma (n = 12), HRV1b-stimulated PBMCs produced significantly less IFN-alpha than PBMCs from participants with eosinophilic (n = 35) and paucigranulocytic asthma (n = 35). Sputum neutrophil proportion and the dose of inhaled corticosteroids were independent predictors of reduced IFN-alpha production after HRV1b exposure. CONCLUSIONS: Antiviral type I IFN production is impaired in those with neutrophilic airway inflammation and in those prescribed high doses of inhaled corticosteroids. Our study is an important step toward identifying those with poorly controlled asthma who might respond best to inhaled IFN therapy during exacerbations. PMID- 26836899 TI - Crises in Sickle Cell Disease. AB - In spite of significant strides in the treatment of sickle cell disease (SCD), SCD crises are still responsible for high morbidity and early mortality. While most patients initially seek care in the acute setting for a seemingly uncomplicated pain episode (pain crisis or vaso-occlusive crisis), this initial event is the primary risk factor for potentially life-threatening complications. The pathophysiological basis of these illnesses is end-organ ischemia and infarction combined with the downstream effects of hemolysis that results from red blood cell sickling. These pathological changes can occur acutely and lead to a dramatic clinical presentation, but are frequently superimposed over a milieu of chronic vasculopathy, immune dysregulation, and decreased functional reserve. In the lungs, acute chest syndrome is a particularly ominous lung injury syndrome with a complex pathogenesis and potentially devastating sequelae, but all organ systems can be affected. It is, therefore, critical to understand the SCD patients' susceptibility to acute complications and their risk factors so that they can be recognized promptly and managed effectively. Blood transfusions remain the mainstay of therapy for all severe acute crises. Recommendations and indications for the safest and most efficient implementation of transfusion strategies in the critical care setting are therefore presented and discussed, together with their pitfalls and potential future therapeutic alternatives. In particular, the importance of extended phenotypic red blood cell matching cannot be overemphasized, due to the high prevalence of severe complications from red cell alloimmunization in SCD. PMID- 26836900 TI - Outcomes of Nurse Practitioner-Delivered Critical Care: A Prospective Cohort Study. AB - BACKGROUND: Acute care nurse practitioners (ACNPs) are increasingly being employed in ICUs to offset physician shortages, but no data exist about outcomes of critically ill patients continuously cared for by ACNPs. METHODS: Prospective cohort study of all admissions to an adult medical ICU in an academic, tertiary care center between January 1, 2011, and December 31, 2013. The primary end point of 90-day survival was compared between patients cared for by ACNP and resident teams using Cox proportional hazards regression. Secondary end points included ICU and hospital mortality and ICU and hospital length of stay. RESULTS: Among 9,066 admissions, there was no difference in 90-day survival for patients cared for by ACNP or resident teams (adjusted hazard ratio [HR], 0.94; 95% CI, 0.85 1.04; P = .21). Although patients cared for by ACNPs had lower ICU mortality (6.3%) than resident team patients (11.6%; adjusted OR, 0.77; 95% CI, 0.63-0.94; P = .01), hospital mortality was not different (10.0% vs 15.9%; adjusted OR, 0.87; 95% CI, 0.73-1.03; P = .11). ICU length of stay was similar between the ACNP and resident teams (3.4 +/- 3.5 days vs 3.7 +/- 3.9 days [adjusted OR, 1.01; 95% CI, 0.93-1.1; P = .81]), but hospital length of stay was shorter for patients cared for by ACNPs (7.9 +/- 11.2 days) than for resident patients (9.1 +/- 11.2 days) (adjusted OR, 0.87; 95% CI, 0.80-0.95; P = .001). CONCLUSION: Outcomes are comparable for critically ill patients cared for by ACNP and resident teams. PMID- 26836903 TI - Complications of Lung Transplantation: A Roentgenographic Perspective. AB - Lung transplantation is now an established treatment for a broad spectrum of end stage pulmonary diseases. According to the International Society for Heart and Lung Transplantation Registry, more than 50,000 lung transplants have been performed worldwide, with nearly 11,000 lung transplant recipients alive in the United States. With the increasing application of lung transplantation, pulmonologists must be cognizant of common complications unique to the postlung transplant period and the associated radiologic findings. The aim of this review is to describe clinical manifestations and prototypical radiographic features of both common and rare complications encountered in lung transplant recipients. PMID- 26836902 TI - Hospitals' Patterns of Use of Noninvasive Ventilation in Patients With Asthma Exacerbation. AB - BACKGROUND: Limited data are available on the use of noninvasive ventilation in patients with asthma exacerbations. The objective of this study was to characterize hospital patterns of noninvasive ventilation use in patients with asthma and to evaluate the association with the use of invasive mechanical ventilation and case fatality rate. METHODS: This cross-sectional study used an electronic medical record dataset, which includes comprehensive pharmacy and laboratory results from 58 hospitals. Data on 13,558 patients admitted from 2009 to 2012 were analyzed. Initial noninvasive ventilation (NIV) or invasive mechanical ventilation (IMV) was defined as the first ventilation method during hospitalization. Hospital-level risk-standardized rates of NIV among all admissions with asthma were calculated by using a hierarchical regression model. Hospitals were grouped into quartiles of NIV to compare the outcomes. RESULTS: Overall, 90.3% of patients with asthma were not ventilated, 4.0% were ventilated with NIV, and 5.7% were ventilated with IMV. Twenty-two (38%) hospitals did not use NIV for any included admissions. Hospital-level adjusted NIV rates varied considerably (range, 0.4-33.1; median, 5.2%). Hospitals in the highest quartile of NIV did not have lower IMV use (5.4% vs 5.7%), but they did have a small but significantly shorter length of stay. Higher NIV rates were not associated with lower risk-adjusted case fatality rates. CONCLUSIONS: Large variation exists in hospital use of NIV for patients with an acute exacerbation of asthma. Higher hospital rates of NIV use does not seem to be associated with lower IMV rates. These results indicate a need to understand contextual and organizational factors contributing to this variability. PMID- 26836904 TI - SERVE-HF: More Questions Than Answers. AB - The recent online publication of the SERVE-HF trial that evaluated the effect of treating central sleep apnea (CSA) with an adaptive servoventilation (ASV) device in patients with heart failure and reduced ejection fraction (HFrEF) has raised serious concerns about the safety of ASV in these patients. Not only was ASV ineffective but post hoc analysis found excess cardiovascular mortality in treated patients. The authors cited as one explanation an unfounded notion that CSA is a compensatory mechanism with a protective effect in HFrEF patients. We believe that there are several possible considerations that are more likely to explain the results of SERVE-HF. In this commentary, we consider methodological issues including the use of a previous-generation ASV device that constrained therapeutic settings to choices that are no longer in wide clinical use. Patient selection, data collection, and treatment adherence as well as group crossovers were not discussed in the trial as potential confounding factors. We have developed alternative reasons that could potentially explain the results and that can be explored by post hoc analysis of the SERVE-HF data. We believe that our analysis is of critical value to the field and of particular importance to clinicians treating these patients. PMID- 26836901 TI - Cardiac Dysfunction After Neurologic Injury: What Do We Know and Where Are We Going? AB - Recent literature has implicated severe neurologic injuries, such as aneurysmal subarachnoid hemorrhage, as a cause of cardiac dysfunction, impaired hemodynamic function, and poor outcomes. Mechanistic links between the brain and the heart have been explored in detail over the past several decades, and catecholamine excess, neuroendocrine dysfunction, and unchecked inflammation all likely contribute to the pathophysiologic process. Although cardiac dysfunction has also been described in other disease paradigms, including septic shock and thermal injury, there is likely a common underlying pathophysiology. In this review, we will examine the pathophysiology of cardiac dysfunction after neurologic injury, discuss the evidence surrounding cardiac dysfunction after different neurologic injuries, and suggest future research goals to gain knowledge and improve outcomes in this patient population. PMID- 26836905 TI - Chronic Pulmonary Complications of Sickle Cell Disease. AB - Sickle cell disease (SCD), the most common genetic hemolytic anemia worldwide, affects 250,000 births annually. In the United States, SCD affects approximately 100,000 individuals, most of African descent. Hemoglobin S (HbS) results from a glutamate-to-valine mutation of the sixth codon of the beta-hemoglobin allele; the homozygous genotype (HbSS) is associated with the most prevalent and severe form of the disease. Other SCD genotypes include HbSC, composed of one HbS allele and one HbC (glutamate-to-lysine mutation) allele; and HbS-beta-thalassemia(0) or HbS-beta-thalassemia(+), composed of one HbS allele and one beta-thalassemia allele with absent or reduced beta-chain production, respectively. Despite advances in care, median survival remains in the fifth decade, due in large part to chronic complications of the disease. Chronic pulmonary complications in SCD are major contributors to this early mortality. Although our understanding of these conditions has improved much over the past 10 to 15 years, there remains no specific treatment for pulmonary complications of SCD. It is unclear whether conventional treatment regimens directed at non-SCD populations have equivalent efficacy in patients with SCD. This represents a critical research need. In this review, the authors review the state-of-the-art understanding of the following pulmonary complications of SCD: (1) pulmonary hypertension; (2) venous thromboembolic disease; (3) sleep-disordered breathing; (4) asthma and recurrent wheezing; and (5) pulmonary function abnormalities. This review highlights the advances as well as the knowledge gaps in this field to update clinicians and other health care providers and to garner research interest from the medical community. PMID- 26836906 TI - Valsalva Maneuver in Pulmonary Arterial Hypertension: Susceptibility to Syncope and Autonomic Dysfunction. AB - BACKGROUND: Patients with pulmonary arterial hypertension (PAH) are routinely instructed to avoid performing the Valsalva maneuver for fear of syncope or sudden cardiac death. The mechanism of this action has not been elucidated. We conducted a case-control trial of nine patients with PAH and 15 healthy control subjects to determine if systemic hemodynamic changes during the Valsalva maneuver in these patients invoke greater susceptibility to syncope than healthy control subjects. Metrics commonly employed in autonomic testing were used to assess the degree of autonomic failure. METHODS: Common Valsalva parameters, including adrenergic baroreflex sensitivity, pressure recovery time, systolic BP (SBP) recovery, diastolic BP (DBP) recovery, mean arterial pressure recovery, and the Valsalva ratio, were calculated. Mann-Whitney U tests were used to compare continuous variables. The primary end point was adrenergic baroreflex sensitivity. RESULTS: Patients with PAH had lower adrenergic baroreflex sensitivity (9.7 +/- 4.6 mm Hg/s vs 18.8 +/- 9.2 mm Hg/s; P = .005), longer pressure recovery time (3.6 +/- 2.5 s vs 1.7 +/- 0.8 s; P = .008), similar SBP recovery (-13 +/- 11 mm Hg vs -12 +/- 23 mm Hg; P = .640), less DBP recovery (-1 +/- 12 mm Hg vs 13 +/- 14 mmHg; P = .025), less mean arterial pressure recovery ( 5 +/- 11 mm Hg vs 5 +/- 17 mm Hg; P = .048), and a decreased Valsalva ratio (1.25 +/- 0.11 vs 1.60 +/- 0.22; P < .001) compared with healthy control subjects. CONCLUSIONS: Compared with healthy control subjects, patients with PAH are more susceptible to syncope during the Valsalva maneuver because of autonomic dysfunction causing cerebral hypoperfusion. These study patients with PAH exhibited a degree of susceptibility to syncope similar to a spectrum of patients with intermediate autonomic failure who typically experience a SBP drop of 10 to 30 mm Hg with standing. PMID- 26836908 TI - Intermittent Hypoxia-Induced Cardiovascular Remodeling Is Reversed by Normoxia in a Mouse Model of Sleep Apnea. AB - BACKGROUND: Intermittent hypoxia (IH) is the principal injurious factor involved in the cardiovascular morbidity and mortality associated with OSA. The gold standard for treatment is CPAP, which eliminates IH and appears to reduce cardiovascular risk. There is no experimental evidence on the reversibility of cardiovascular remodeling after IH withdrawal. The objective of the present study is to assess the reversibility of early cardiovascular structural remodeling induced by IH after resumption of normoxic breathing in a novel recovery animal model mimicking OSA treatment. METHODS: We investigated cardiovascular remodeling in C57BL/6 mice exposed to IH for 6 weeks vs the normoxia group and its spontaneous recovery after 6 subsequent weeks under normoxia. RESULTS: Aortic expansive remodeling was induced by IH, with intima-media thickening and without lumen perimeter changes. Elastic fiber network disorganization, fragmentation, and estrangement between the end points of disrupted fibers were increased by IH. Extracellular matrix turnover was altered, as visualized by collagen and mucoid interlaminar accumulation. Furthermore, left ventricular perivascular fibrosis was increased by IH, whereas cardiomyocytes size was unaffected. These cardiovascular remodeling events induced by IH were normalized after recovery in normoxia, mimicking CPAP treatment. CONCLUSIONS: The early structural cardiovascular remodeling induced by IH was normalized after IH removal, revealing a novel recovery model for studying the effects of OSA treatment. Our findings suggest the clinical relevance of early detection and effective treatment of OSA in patients to prevent the natural course of cardiovascular diseases. PMID- 26836907 TI - Airway Surfactant Protein D Deficiency in Adults With Severe Asthma. AB - BACKGROUND: Surfactant protein D (SP-D) is an essential component of the innate immune defense against pathogens within the airways. SP-D also regulates allergic inflammation and promotes the removal of apoptotic cells. SP-D dysregulation is evident in several pulmonary diseases. Our aim was to investigate whether airway and serum levels of SP-D are altered in treatment-resistant severe asthma. METHODS: SP-D concentrations were measured in matched serum and BAL samples collected from 10 healthy control subjects (HC) and 50 patients with asthma (22 with mild asthma [MA] and 28 with severe asthma [SA]). These samples were also evaluated by using Western blot analysis to investigate variations in SP-D size. RESULTS: SP-D levels in BAL samples were significantly lower in SA compared with HC and MA (P < .001) and inversely correlated with BAL eosinophil cationic protein concentrations in SA (P < .01). Serum SP-D was significantly increased in SA compared with HC and MA (P < .001), and BAL/serum ratios were significantly lower in SA compared with HC and MA (P < .001). Reduced SP-D levels in BAL samples, with concomitant increases in serum in SA, were associated with degraded fragments of SP-D in the serum and increased BAL neutrophil counts and lipopolysaccharide levels. CONCLUSIONS: These findings suggest defective innate immunity within the airways in SA, as reflected by low BAL SP-D concentrations and altered bacterial presence with airway neutrophilia. Furthermore, BAL SP-D leakage into the serum in patients with SA may provide a peripheral blood biomarker, reflecting increased epithelial damage and/or epithelial permeability within the peripheral airways. PMID- 26836909 TI - CT Imaging Phenotypes of Pulmonary Fibrosis in the MUC5B Promoter Site Polymorphism. AB - BACKGROUND: To determine the effect of the MUC5B promoter polymorphism (rs35705950) on the CT imaging appearance of pulmonary fibrosis. METHODS: High resolution CT scans of 1,764 subjects were scored as part of a, genomewide association study with institutional review board approval; 1,491 of these had pulmonary fibrosis on CT scans and were included in the study. Two thoracic radiologists independently scored CT scans systematically. Discrepancies were resolved by a third thoracic radiologist. All patients were genotyped specifically for the rs35705950 single-nucleotide polymorphism (SNP). Two-tailed Fisher exact or chi(2) tests and Student t tests or Mann-Whitney U tests were used to compare proportions and means, respectively. RESULTS: The major and minor alleles at the rs35705950 SNP are guanine (G) and thymine (T), respectively: 514 were homozygous for the major allele (G group), and 977 were heterozygous or homozygous for the minor allele (T group). The G group had a higher proportion than the T group with ground-glass opacity (62.1% vs 54.2%; P = .04). There was no significant difference between the G and T groups regarding presence of honeycombing. The T group showed a significantly higher subpleural axial distribution of fibrosis than did the G group (62.3% vs 42.2%; P < .0001). The T group showed a lower proportion of diagnoses inconsistent with usual interstitial pneumonitis (UIP; 20.3% compared with 30.5% for the G group) and a greater proportion of confident (probable UIP and UIP) UIP diagnoses (43.8% compared with 32.6% for the G group). CONCLUSIONS: The MUC5B promoter polymorphism identifies a pattern of fibrosis that is different from other causes of fibrosis and may respond differently to potential therapies. PMID- 26836910 TI - Effect of Age on Phenotype and Outcomes in Pulmonary Arterial Hypertension Trials. AB - BACKGROUND: In recent years, the population of patients with pulmonary arterial hypertension (PAH) has changed dramatically, including more advanced age at diagnosis. We hypothesized that older patients have a distinct clinical profile with different disease characteristics and response to intervention. METHODS: All previously published treatment studies for PAH conducted by United Therapeutics including seven randomized, placebo-controlled trials and one extension study were included and analyzed to assess the association of age with various demographic, functional, hemodynamic, and outcome variables. RESULTS: A total of 2,627 patients across three age groups were included: <= 50 (n = 1,438, 54.7%), 51 to 64 (n = 780, 29.7%), and >= 65 years (n = 409, 15.6%). In comparison with the youngest group, the oldest age group had higher proportions of connective tissue disease-associated etiology (range across the studies, 27%-49% vs 13% 21%), higher proportions of New York Heart Association Functional classes III and IV (74%-91% vs 57%-84%), shorter baseline 6-min walk distance (6MWD) (261-316 vs 335-371 m), better hemodynamic measurements including lower baseline mean pulmonary artery pressure (48-51 vs 58-63 mmHg), and smaller changes in 6MWD from baseline to endpoint (-5.6 to 24 vs 14-43 m). Age remained associated with change in 6MWD when adjusting for covariates in multivariate analyses. CONCLUSIONS: For the first time, using data from large randomized controlled trials, this study characterizes the different phenotype and outcomes of older patients with PAH, which includes different disease etiology, diminished functional status, and decreased response to intervention. This may have significant implications for the management of this patient population and design of future therapy trials. PMID- 26836911 TI - Cohort Study on the Management of Cancer-Associated Venous Thromboembolism Aimed at the Safety of Stopping Anticoagulant Therapy in Patients Cured of Cancer. AB - BACKGROUND: After diagnosis of cancer-associated VTE, guidelines recommend considering the continuation of anticoagulant treatment until the patient is cured of cancer, although the safety of stopping anticoagulant treatment after the patient is cured has never been evaluated. METHODS: We conducted a cohort study in consecutive patients in whom cancer-associated VTE was diagnosed at the Leiden University Medical Center between January 2001 and January 2010 and monitored for the effect of cancer treatment, occurrence of recurrent VTE, major hemorrhage, and death. RESULTS: Of the 358 patients with cancer-associated VTE, anticoagulant treatment was continued until the death of 207 patients. In another 12 patients anticoagulant treatment was continued because of an alternative indication despite their being cured of cancer. Anticoagulant treatment was stopped in 50 patients for reasons other than major hemorrhage despite active cancer, in 21 patients after major hemorrhage, and in 68 patients after they had been cured of cancer. Among these 68 patients, 10 patients received a diagnosis of symptomatic recurrent VTE during a cumulative follow-up of 311 years, resulting in an incidence rate of 3.2 per 100 patient-years (95% CI, 1.5-5.9). Seven of these 10 patients with recurrent VTE experienced a cancer relapse during follow-up. For the 50 patients who stopped anticoagulant treatment despite active cancer the recurrent VTE incidence rate was 19 per 100 patient-years (11 events during 59 years of follow-up; 95% CI, 9.3-33). CONCLUSIONS: Our data support the recommendation to stop anticoagulant treatment of cancer-associated VTE in patients cured of cancer. A cancer relapse seems to be a strong risk factor for recurrent symptomatic VTE. PMID- 26836913 TI - Pulmonary Involvement in Patients With Hemophagocytic Lymphohistiocytosis. AB - BACKGROUND: Acquired hemophagocytic lymphohistiocytosis (HLH) is a life threatening event that usually occurs as a complication of immunodeficiency. Lung involvement in HLH has received little attention. This article describes lung involvement in HLH and assesses whether it affects the prognosis. METHODS: We retrospectively studied 219 patients with HLH admitted to a national reference center over a 14-year period, including 118 (54%) with lung involvement. RESULTS: Dyspnea and cough were the most common onset symptoms. Radiographs revealed interstitial infiltrates with centrilobular nodules, ill-defined consolidation, or localized ground-glass opacities. Pleural effusions and mediastinal lymphadenopathies were found in approximately one-half of the patients. One or more causes of lung involvement were documented in 91 of 118 patients (77.1%) and included infection (n = 52), pulmonary edema (n = 34), and malignancies (n = 22 [mostly lymphoma]). HLH-specific treatment combined with treatment of the cause of lung involvement improved respiratory function in only 67 of the 188 patients (56.7%). Hospital mortality was higher in patients with lung involvement (52.5% vs 20%). Infection as the cause of lung involvement was the only determinant of death (56% vs 30%; P = .004). CONCLUSIONS: Lung involvement is common and of poor prognosis in patients with HLH. Studies should assess whether specific diagnostic and therapeutic strategies are warranted in patients with HLH and lung involvement. PMID- 26836912 TI - Lung Function Trajectories in World Trade Center-Exposed New York City Firefighters Over 13 Years: The Roles of Smoking and Smoking Cessation. AB - BACKGROUND: World Trade Center (WTC)-exposed Fire Department of the City of New York firefighters lost, on average, 10% of lung function after September 11, 2011, and >10% developed new obstructive airways disease. There was little recovery (on average) over the first 6 years. Follow-up into the next decade allowed us to determine the longer-term exposure effects and the roles of cigarette smoking and cessation on lung function trajectories. METHODS: We examined serial measurements of FEV1 from March 11, 2000, to September 10, 2014, among 10,641 WTC-exposed Fire Department of the City of New York firefighters with known smoking and body weight histories. RESULTS: The median number of FEV1 measurements during follow-up was 9; 15% of firefighters arrived at the WTC during the morning of September 11, 2001; and 65% never smoked. Firefighters arriving the morning of September 11, 2001 averaged lower lung function than did lesser exposed firefighters; this difference remained significant during most of follow-up (P < .05). Never smokers had significantly better lung function than current smokers; former smokers fell in between, depending upon their cessation date. Those arriving the morning of September 11, 2001 were more likely to have an FEV1 < lower limits of normal compared with those arriving between September 13, 2001, and September 24, 2001 (OR = 1.70, P < .01). Current smokers were more likely to have an FEV1 < lower limits of normal compared with never smokers (OR = 2.06, P < .01), former smokers who quit before September 11, 2001 (OR = 1.96, P < .01), or those who quit between September 11, 2001 and March 10, 2008 (OR = 1.49, P < .01). CONCLUSIONS: Thirteen years after September 11, 2001, most firefighters continued to show a lack of lung function recovery, with the trajectory of decline differing by WTC exposure and smoking status. Unlike the immutable effect of WTC exposure, we demonstrated the benefit on lung function of smoking cessation in this unique occupational/environmental cohort. PMID- 26836915 TI - Finding Common Ground: Professionalism and Acthar Prescribing Practices. PMID- 26836914 TI - Drug Treatment of Idiopathic Pulmonary Fibrosis: Systematic Review and Network Meta-Analysis. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a form of chronic progressive fibrosing interstitial lung disease of unknown origin. Recently, nintedanib and pirfenidone demonstrated efficacy in slowing disease progression and were approved by the US Food and Drug Administration. Although numerous treatments have been evaluated in IPF, none have shown significant decreases in mortality. The objective of this study was to identify all pharmacologic treatments evaluated for IPF and analyze their efficacy via Bayesian network meta-analysis and pairwise indirect treatment comparisons. This review did not evaluate the effect of steroid therapy. METHODS: We searched MEDLINE, Embase, and the Cochrane Library for studies published on or before August 2014. Studies were required to contain a randomized evaluation of nonsteroidal drug therapy for treatment of IPF and be published in English. Key outcomes of interest for this analysis were pulmonary function as measured by FVC as well as all-cause and respiratory specific death. All outcomes were analyzed via a Bayesian framework. RESULTS: Our review identified 30 eligible studies that evaluated 16 unique treatments. Under both the fixed-effect and random-effect models for respiratory-specific mortality, no treatments performed better than placebo. For all-cause mortality, pirfenidone and nintedanib had effects approaching significance with credible intervals slightly crossing the null under a fixed-effect model. Notably, for respiratory-specific mortality, all-cause mortality, and decline in percent predicted FVC, nintedanib and pirfenidone were virtually indistinguishable and no clear advantage was detected. CONCLUSIONS: Although two treatments have been approved for IPF on the basis of reduced decline in pulmonary function, neither one has a clear advantage on mortality outcomes. PMID- 26836916 TI - Is There Any Reliable Clinical Evidence to Suggest That Acthar Is More Effective Than Other Forms of Corticosteroids in Treating Sarcoidosis and Other Diseases It Is Being Marketed to Treat? PMID- 26836917 TI - Recent Marijuana Use and Associations With Exhaled Nitric Oxide and Pulmonary Function in Adults in the United States. AB - BACKGROUND: The medical and recreational use of marijuana is now legal in some parts of the United States; the health effects are unknown. We aimed to evaluate associations between recent marijuana use and exhaled nitric oxide (eNO) and pulmonary function. METHODS: We performed a cross-sectional study of 10,327 US adults participating in the National Health and Nutrition Examination Survey in the years 2007 to 2012. We examined associations between marijuana use and eNO, FEV1, FVC, the FEV1/FVC ratio, and forced expiratory flow (midexpiratory phase) (FEF25%-75%) by weighted linear regression. RESULTS: In the study population, there were 4,797 never users, 4,084 past marijuana users, 555 participants who used marijuana 5 to 30 days before the examination, and 891 participants who used marijuana 0 to 4 days before the examination. Current marijuana use in the past 4 days was associated with 13% lower eNO (95% CI, -18% to 8%). FVC was higher in past users (75 mL; 95% CI, 38-112) and current users in the past 5 to 30 days (159 mL; 95% CI, 80-237) and in users within 0 to 4 days of the examination (204 mL; 95% CI, 139-270) compared with never users. All associations remained unchanged and statistically significant in sensitivity analyses excluding current and past tobacco users. CONCLUSIONS: Current marijuana use was associated with lower levels of eNO and higher FVC. The lower eNO in marijuana smokers suggests that short-term exposure to marijuana may, like tobacco, acutely affect the pulmonary vascular endothelium and impair airflow through the small airways. PMID- 26836918 TI - Pleural Effusions at First ED Encounter Predict Worse Clinical Outcomes in Patients With Pneumonia. AB - BACKGROUND: Pleural effusions are present in 15% to 44% of hospitalized patients with pneumonia. It is unknown whether effusions at first presentation to the ED influence outcomes or should be managed differently. METHODS: We studied patients in seven hospital EDs with International Statistical Classification of Disease and Health Related Problems-Version 9 codes for pneumonia, or empyema, sepsis, or respiratory failure with secondary pneumonia. Patients with no confirmatory findings on chest imaging were excluded. Pleural effusions were identified with the use of radiographic imaging. RESULTS: Over 24 months, 4,771 of 458,837 adult ED patients fulfilled entry criteria. Among the 690 (14.5%) patients with pleural effusions, their median age was 68 years, and 46% were male. Patients with higher Elixhauser comorbidity scores (OR, 1.13 [95% CI, 1.09-1.18]; P < .001), brain natriuretic peptide levels (OR, 1.20 [95% CI, 1.12-1.28]; P < .001), bilirubin levels (OR, 1.07 [95% CI, 1.00-1.15]; P = .04), and age (OR, 1.15 [95% CI, 1.09 1.21]; P < .001) were more likely to have parapneumonic effusions. In patients without effusion, electronic version of CURB-65 (confusion, uremia, respiratory rate, BP, age >= 65 years accurately predicted mortality (4.7% predicted vs 5.0% actual). However, eCURB underestimated mortality in those with effusions (predicted 7.0% vs actual 14.0%; P < .001). Patients with effusions were more likely to be admitted (77% vs 57%; P < .001) and had a longer hospital stay (median, 2.8 vs 1.3 days; P < .001). After severity adjustment, the likelihood of 30-day mortality was greater among patients with effusions (OR, 2.6 [CI, 2.0 3.5]; P < .001), and hospital stay was disproportionately longer (coefficient, 0.22 [CI, 0.14-0.29]; P < .001). CONCLUSIONS: Patients with pneumonia and pleural effusions at ED presentation in this study were more likely to die, be admitted, and had longer hospital stays. Why parapneumonic effusions are associated with adverse outcomes, and whether different management of these patients might improve outcome, needs urgent investigation. PMID- 26836919 TI - The Critically Ill Kidney Transplant Recipient: A Narrative Review. AB - Kidney transplantation is the most common solid organ transplantation performed worldwide. Up to 6% of kidney transplant recipients experience a life-threatening complication that requires ICU admission, chiefly in the late posttransplantation period (>= 6 months). Acute respiratory failure and septic shock are the main reasons for ICU admission. Cardiac pulmonary edema, bacterial pneumonia, acute graft pyelonephritis, and bloodstream infections account for the vast majority of diagnoses in the ICU. Pneumocystis jirovecii pneumonia is the most common opportunistic infection, and one-half of the patients so infected require mechanical ventilation. The incidence of cytomegalovirus visceral infections in the era of preemptive therapy has dramatically decreased. Drug-related neutropenia, sirolimus-related pneumonitis, and posterior reversible encephalopathy syndrome are among the most common immunosuppression-associated toxic effects. Importantly, the impact of critical illness on graft function is worrisome. Throughout the ICU stay, acute kidney injury is common, and about 40% of the recipients require renal replacement therapy. One-half of the patients are discharged alive and free from dialysis. Hospital mortality can reach 30% and correlates with acute illness severity and reason for ICU admission. Transplant characteristics are not predictors of short-term survival. Graft survival depends on pre-ICU graft function, disease severity, and renal toxicity of ICU investigations and treatments. PMID- 26836920 TI - Longitudinal Measurement of Pleural Fluid Biochemistry and Cytokines in Malignant Pleural Effusions. AB - BACKGROUND: Malignant pleural effusion (MPE) is common. Existing literature on pleural fluid compositions is restricted to cross-sectional sampling with little information on longitudinal changes of fluid biochemistry and cytokines with disease progression. Indwelling pleural catheters provide the unique opportunity for repeated sampling and longitudinal evaluation of MPE, which may provide insight into tumor pathobiology. METHODS: We collected 638 MPE samples from 103 patients managed with indwelling pleural catheters over 95 days (median, range 0 735 days) and analyzed them for protein, pH, lactate dehydrogenase, and glucose levels. Peripheral blood was quantified for hematocrit, platelets, leukocytes, protein, and albumin. Cytokine levels (monocyte chemotactic protein [MCP]-1; vascular endothelial growth factor; interleukin-6, -8, and -10; tumor necrosis factor-alpha; and interferon-gamma) were determined in 298 samples from 35 patients with mesothelioma. Longitudinal changes of all parameters were analyzed using a linear mixed model. RESULTS: Significant decreases were observed over time in pleural fluid protein by 8 g/L per 100 days (SE, 1.32; P < .0001) and pH (0.04/100 days; SE, 0.02; P = .0203), accompanied by a nonsignificant rise in lactate dehydrogenase. The ratio of pleural fluid to serum protein decreased by 0.06/100 days (SE, 0.02; P = .04). MPEs from mesothelioma (n = 63) had lower pleural fluid glucose (P = .0104) at baseline and a faster rate of decline in glucose (P = .0423) when compared with non-mesothelioma effusions (n = 38). A progressive rise in mesothelioma pleural fluid concentration of [log] MCP-1 ([log] 0.37 pg/mL per 100 days; SE, 0.13; P = .0046), but not of other cytokines, was observed. CONCLUSIONS: MPE fluids become less exudative and more acidic over the disease course. The rise in MCP-1 levels suggests a pathobiological role in MPE. PMID- 26836921 TI - Chronic Hypersensitivity Pneumonitis With a Usual Interstitial Pneumonia-Like Pattern: Correlation Between Histopathologic and Clinical Findings. AB - BACKGROUND: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of environmental antigens. The relationship between clinical, radiologic, and histopathologic findings of chronic HP remains unclear. METHODS: Sixteen patients with proven chronic bird-related HP with a usual interstitial pneumonia-like pattern were analyzed retrospectively. Histopathologic findings were semiquantitatively assessed and compared with clinical and radiologic findings. We also evaluated the histopathologic findings affecting prognosis. RESULTS: The extent of centrilobular fibrosis was negatively correlated with Pao2 (r = -0.55, P = .03). The extent of bridging fibrosis was positively correlated with the ratio of maximal expiratory flow at 50% of forced vital capacity to that at 25% (r = 0.60, P = .02). Patients with a greater extent of fibroblastic foci (FF) had more radiologic reticulation (P = .01), honeycombing (P = .01), and traction bronchiectasis (P = .02), and had significantly shorter survival time (P = .01) than patients with a lesser extent of FF. Multivariate analysis showed that the extent of FF was a significant prognostic factor (hazard ratio, 2.36; 95% confidence interval, 1.02-5.48; P = .04). CONCLUSIONS: Our findings demonstrated that the extent of FF was significantly associated with reticulation, honeycombing, and traction bronchiectasis on high-resolution CT scanning. Moreover, the extent of FF could be a useful predictor of mortality in chronic HP with a usual interstitial pneumonia-like pattern. PMID- 26836922 TI - Major Bleeding and Hemorrhagic Stroke With Direct Oral Anticoagulants in Patients With Renal Failure: Systematic Review and Meta-Analysis of Randomized Trials. AB - BACKGROUND: Direct oral anticoagulants (DOACs) are used as an alternative for traditional antithrombotic therapy. However, the safety profile of DOACs in patients with renal failure (RF) has not been determined. METHODS: A systematic review was performed assessing the reported safety of DOACs compared with vitamin K antagonists (VKAs) in patients with RF and estimated creatinine clearance (eCrCL) < 50 mL/min and eCrCL 50 to 80 mL/min. MEDLINE, EMBASE, Cochrane, and the Clinical Trials Registry (ClinicalTrials.gov) were searched for randomized clinical trials up to November 2015. The data were pooled by using both traditional frequentist and Bayesian random effects models. RESULTS: Nine trials met the inclusion criteria. Among 94,897 participants, 54,667 (58%) had RF. Compared with VKAs, DOACs were associated with a significantly decreased risk for major bleeding in patients with eCrCL 50 to 80 mL/min (risk ratio, 0.87 [95% CI, 0.81-0.93]) and a nonsignificant decrease in the risk for major bleeding in patients with eCrCL < 50 mL/min (risk ratio, 0.83 [95% CI, 0.68-1.02]); there was evidence of significant heterogeneity. Indirect comparisons, using Bayesian network analysis, indicated that apixaban was associated with a decreased rate of major bleeding compared with other DOACs in patients with eCrCL < 50 mL/min. DOACs were associated with a significant decrease in the risk for hemorrhagic stroke compared with VKAs in patients with eCrCL < 50 mL/min and 50 to 80 mL/min. CONCLUSIONS: As a class, DOACs are associated with a reduced risk for hemorrhagic stroke compared with VKAs in patients with RF. However, DOACs may differ from each other in their relative risk for major bleeding in patients with eCrCL < 50 mL/min. TRIAL REGISTRY: PROSPERO registry; No.: CRD42014013730; URL: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014013730. PMID- 26836923 TI - Associations of Early Life Exposures and Environmental Factors With Asthma Among Children in Rural and Urban Areas of Guangdong, China. AB - BACKGROUND: Environmental factors may play important roles in asthma, but findings have been inconsistent. OBJECTIVE: The goal of this study was to determine the associations between early life exposures, environmental factors, and asthma in urban and rural children in southeast China. METHODS: A screening questionnaire survey was conducted in 7,164 children from urban Guangzhou and 6,087 from rural Conghua. In the second stage, subsamples of 854 children (419 from Guangzhou, 435 from Conghua) were recruited for a case-control study that included a detailed questionnaire enquiring on family history, early life environmental exposures, dietary habits, and laboratory tests (including histamine airway provocation testing, skin prick tests, and serum antibody analyses). House dust samples from 76 Guangzhou families and 80 Conghua families were obtained to analyze levels of endotoxins, house dust mites, and cockroach allergens. RESULTS: According to the screening survey, the prevalence of physician-diagnosed asthma was lower in children from Conghua (3.4%) than in those from Guangzhou (6.9%) (P < .001). A lower percentage of asthma was reported in rural subjects compared with urban subjects (2.8% vs. 29.4%; P < .001) in the case-control study. Atopy (OR, 1.91 [95% CI, 1.58-2.29]), parental atopy (OR, 2.49 [95% CI, 1.55-4.01]), hospitalization before 3 years of age (OR, 2.54 [95% CI, 1.37-4.70]), high consumption of milk products (OR, 1.68 [95% CI, 1.03 2.73]), and dust Dermatophagoides farinae group 1 allergen (OR, 1.71 [95% CI, 1.34-2.19]) were positively associated with asthma. Living in a crop-farming family at < 1 year of age (OR, 0.15 [95% CI, 0.08-0.32]) and dust endotoxin levels (OR, 0.69 [95% CI, 0.50-0.95]) were negatively associated with asthma. CONCLUSIONS: Rural children from an agricultural background exhibited a reduced risk of asthma. Early life exposure to crop farming and high environmental endotoxin levels might protect the children from asthma in southern China. PMID- 26836924 TI - Nonlinear Imputation of Pao2/Fio2 From Spo2/Fio2 Among Patients With Acute Respiratory Distress Syndrome. AB - BACKGROUND: ARDS is an important clinical problem. The definition of ARDS requires testing of arterial blood gas to define the ratio of Pao2 to Fio2 (Pao2/Fio2 ratio). However, many patients with ARDS do not undergo blood gas measurement, which may result in underdiagnosis of the condition. As a consequence, a method for estimating Pao2 on the basis of noninvasive measurements is desirable. METHODS: Using data from three ARDS Network studies, we analyzed the enrollment arterial blood gas measurements to compare nonlinear with linear and log-linear imputation methods of estimating Pao2 from percent saturation of hemoglobin with oxygen as measured by pulse oximetry (Spo2). We compared mortality on the basis of various measured and imputed Pao2/Fio2 ratio cutoffs to ensure clinical equivalence. RESULTS: We studied 1,184 patients, in 707 of whom the Spo2 <= 96%. Nonlinear imputation from the Spo2/Fio2 ratio resulted in lower error than linear or log-linear imputation (P < .001) for patients with Spo2 <= 96% but was equivalent to log-linear imputation in all patients. Ninety-day hospital mortality was 26% to 30%, depending on the Pao2/Fio2 ratio, whether nonlinearly imputed or measured. On multivariate regression, the association between imputed and measured Pao2 varied by use of vasopressors and Spo2. CONCLUSIONS: A nonlinear equation more accurately imputes Pao2/Fio2 from Spo2/Fio2 than linear or log-linear equations, with similar observed hospital mortality depending on Spo2/Fio2 ratio vs measured Pao2/Fio2 ratios. While further refinement through prospective validation is indicated, a nonlinear imputation appears superior to prior approaches to imputation. PMID- 26836925 TI - Metabolic Syndrome and the Lung. AB - A link between metabolic syndrome (MetS) and lung diseases has been observed in several cross-sectional and longitudinal studies. This syndrome has been identified as an independent risk factor for worsening respiratory symptoms, greater lung function impairment, pulmonary hypertension, and asthma. This review will discuss several potential mechanisms to explain these associations, including dietary factors and the effect of adiposity and fat-induced inflammation on the lungs, and the role of other comorbidities that frequently coexist with MetS, such as OSA and obesity. In contrast to the well-known association between asthma and obesity, the recognition that MetS affects the lung is relatively new. Although some controversy remains as to whether MetS is a unique disease entity, its individual components have independently been associated with changes in pulmonary function or lung disease. There is, however, uncertainty as to the relative contribution that each metabolic factor has in adversely affecting the respiratory system; also, it is unclear how much of the MetS-related lung effects occur independently of obesity. In spite of these epidemiological limitations, the proposed mechanistic pathways strongly suggest that this association is likely to be causal. Given the wide prevalence of MetS in the general population, it is imperative that we continue to further understand how this metabolic disorder impacts the lung and how to prevent its complications. PMID- 26836926 TI - Age-Related Differences in the Rate, Timing, and Diagnosis of 30-Day Readmissions in Hospitalized Adults With Asthma Exacerbation. AB - BACKGROUND: Reducing hospital readmissions has attracted attention from many stakeholders. However, the characteristics of 30-day readmissions after asthma related hospital admissions in adults are not known. It is also unclear whether older adults are at higher risk of 30-day readmission. OBJECTIVES: To investigate the rate, timing, and principal diagnosis of 30-day readmissions in adults with asthma and to determine age-related differences. METHODS: Retrospective cohort study of adults hospitalized for asthma exacerbation using the population-based inpatient samples of three states (California, Florida, and Nebraska) from 2005 through 2011. Patients were categorized into three age groups: younger (18-39 years), middle aged (40-64 years), and older (>= 65 years) adults. Outcomes were 30-day all-cause readmission rate, timing, and principal diagnosis of readmission. RESULTS: Of 301,164 asthma-related admissions at risk for 30-day readmission, readmission rate was 14.5%. Compared with younger adults, older adults had significantly higher readmission rates (10.1% vs 16.5%; OR, 2.15 [95% CI, 2.07-2.23]; P < .001). The higher rate attenuated with adjustment (OR, 1.19 [95% CI, 1.13-1.26]; P < .001), indicating that most of the age-related difference is explained by sociodemographics and comorbidities. For all age groups, readmission rate was highest in the first week after discharge and declined thereafter. Overall, only 47.1% of readmissions were assigned respiratory diagnoses (asthma, COPD, pneumonia, and respiratory failure). Older adults were more likely to present with nonrespiratory diagnoses (41.7% vs 53.8%; P < .001). CONCLUSIONS: After asthma-related admission, 14.5% of patients had 30 day readmission with wide range of principal diagnoses. Compared with younger adults, older adults had higher 30-day readmission rates and proportions of nonrespiratory diagnoses. PMID- 26836927 TI - The Effects of Azithromycin in Treatment-Resistant Cough: A Randomized, Double Blind, Placebo-Controlled Trial. AB - BACKGROUND: Chronic cough is a common clinical problem worldwide. Although many patients have underlying precipitating conditions such as asthma, gastroesophageal reflux, or rhinitis, many remain symptomatic despite treating these conditions. New approaches are needed for the treatment of this group of patients. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to determine whether 250 g of azithromycin three times a week for 8 weeks would affect the Leicester Cough Questionnaire (LCQ) score in 44 patients with treatment-resistant cough. Cough severity on a visual analog scale and bronchial exhaled nitric oxide were measured as secondary outcomes. RESULTS: There was a clinically important improvement in LCQ score with azithromycin (mean change, 2.4; 95% CI, 0.5 to 4.2) but not placebo (mean change, 0.7; 95% CI, -0.6 to 1.9), but the between-group difference was not statistically significant (P = .12). There were no significant between-group differences for any of the secondary outcome measures. Looking at subgroups of responders, there was a large and significant improvement in LCQ score in patients with chronic cough and a concurrent diagnosis of asthma who were treated with azithromycin (mean, 6.19; 95% CI, 4.06 to 8.32). CONCLUSIONS: Treatment with low-dose azithromycin for 8 weeks did not significantly improve LCQ score compared with placebo. The use of macrolides for treatment-resistant cough cannot be recommended from this study, but they may have a place in the treatment of chronic cough associated with asthma; this is worthy of further investigation. TRIAL REGISTRY: WHO International Clinical Trials Registry; No.: ISRCTN75749391. URL: http://apps.who.int. PMID- 26836929 TI - The Clinical Value of Deflation Cough in Chronic Coughers With Reflux Symptoms. AB - BACKGROUND: Patients with deflation cough (DC), the cough-like expulsive effort(s) evoked by maximal lung emptying during a slow vital capacity maneuver, also present symptoms of gastroesophageal reflux. DC can be inhibited by prior intake of antacids. We wished to assess DC prevalence and association between DC and chemical characteristics of refluxate in patients with gastroesophageal reflux symptoms. METHODS: A total of 157 consecutive outpatients underwent DC assessment and 24-h multichannel intraluminal impedance pH (MII-pH) monitoring; 93/157 also had chronic cough. Patients performed two to four slow vital capacity maneuvers and DC was detected aurally. Subsequently, they underwent 24-h MII-pH monitoring, the outcomes of which were defined as abnormal when acid or non-acid reflux events were > 73. RESULTS: DC occurred in 46/157 patients, 18 of whom had abnormal MII-pH outcomes; 28 of the remaining 111 patients without DC also had abnormal MII-pH findings. Thus, in the patients as a group, there was no association between DC and MII-pH outcomes. DC occurred in 40/93 of the chronic coughers; 15 of whom had acid reflux. All but 2 of the 53 patients without DC had normal MII-pH outcomes (P < .001), and the negative predictive value of DC for excluding acid reflux was 96.2%. At follow-up, 65% of coughers showed significant improvement after treatment. CONCLUSIONS: The overall prevalence of DC was 29%, increasing to 43% in chronic coughers in whom the absence of DC virtually excludes acid reflux. Therefore, DC assessment may represent a useful screening test for excluding acid reflux in chronic coughers with reflux symptoms. PMID- 26836928 TI - Regulatory T Cell Dysfunction in Idiopathic, Heritable and Connective Tissue Associated Pulmonary Arterial Hypertension. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) encompasses a group of conditions with distinct causes. Immunologic disorders are common features of all forms of PAH and contributes to both disease susceptibility and progression. Regulatory T lymphocytes (Treg) are dysfunctional in patients with idiopathic PAH (iPAH) in a leptin-dependent manner. However, it is not known whether these abnormalities are specific to iPAH. Hence, we hypothesized that (1) Treg dysfunction is also present in heritable (hPAH) and connective tissue disease associated PAH (CTD-PAH); (2) defective leptin-dependent signaling is present in hPAH and CTD-PAH and could contribute to Treg dysfunction; (3) modulating the leptin axis in vivo could protect against Treg dysfunction; and (4) restoration of Treg activity could limit or reverse experimental chronic hypoxia-induced pulmonary hypertension in vivo. METHODS: We analyzed 62 patients with PAH (30 with iPAH, 18 with hPAH, and 14 with CTD-PAH), 7 patients with CTD without PAH, and 20 healthy control subjects. RESULTS: Our results indicate that Treg are dysfunctional in all PAH forms tested, as well as in patients with CTD without PAH. Importantly, the leptin axis is crucial in Treg dysfunction in patients with iPAH and those with CTD (with or without PAH), whereas in patients with hPAH, Treg are altered in a leptin-independent manner. We found that leptin receptor deficient rats, which develop less severe hypoxia-induced pulmonary hypertension, are protected against decreased Treg function after hypoxic exposure. CONCLUSIONS: Taken together, our results suggest that Treg dysfunction is common to all forms of PAH and may contribute to the development and the progression of the disease. PMID- 26836930 TI - Persistent Challenges in Pediatric Pulmonary Hypertension. AB - Pulmonary hypertension and related pulmonary vascular diseases cause significant morbidities and high mortality and present many unique challenges toward improving outcomes in neonates, infants, and children. Differences between pediatric and adult disease are reflected in controversies regarding etiologies, classification, epidemiology, diagnostic evaluations, and therapeutic interventions. This brief review highlights several key topics reflecting recent advances in the field and identifies persistent gaps in our understanding of clinical pediatric pulmonary hypertension. PMID- 26836931 TI - Validity of Fractional Exhaled Nitric Oxide in Diagnosis of Corticosteroid Responsive Cough. AB - BACKGROUND: Whether fractional exhaled nitric oxide (FeNO) measurement alone or combined with sputum eosinophil and atopy is useful in predicting corticosteroid responsive cough (CRC) and non-CRC (NCRC) is not clear. METHODS: A total of 244 patients with chronic cough and 59 healthy subjects as control were enrolled. The causes of chronic cough were confirmed according to a well-established diagnostic algorithm. FeNO measurement and induced sputum for differential cell were performed in all subjects. RESULTS: CRC occurred in 139 (57.0%) patients and NCRC occurred in 105. The FeNO level in CRC significantly correlated with sputum eosinophils (rs = 0.583, P < .01). The median (quarter) of FeNO level in CRC was significantly higher than NCRC (32.0 ppb [19.0-65.0 ppb] vs 15.0 ppb [11.0-22.0 ppb], P < .01). FeNO of 31.5 ppb had a sensitivity and specificity of 54.0% and 91.4%, respectively, in predicting CRC from chronic cough, with a positive predictive value of 89.3% and a negative predictive value of 60.0%. If the patients had a combination of low level of FeNO ( < 22.5 ppb), normal sputum eosinophil ( < 2.5%), and absence of atopy, the sensitivity and specificity would be 30.3% and 93.5% for predicting NCRC. CONCLUSIONS: In our cohort, a high level (>= 31.5 ppb) of FeNO indicates more likelihood of CRC, but the sensitivity is insufficient to rule out a diagnosis of CRC. A combination of low-level FeNO, normal sputum eosinophil, and absence of atopy suggests a lower likelihood of CRC. PMID- 26836932 TI - Spectrum Analysis of Endobronchial Ultrasound Radiofrequency of Lymph Nodes in Patients With Lung Cancer. AB - OBJECTIVE: The aim of this study was to analyze the spectral features of the radiofrequency of lymph nodes during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and to determine its diagnostic value for detecting metastatic nodes in patients with lung cancer. METHODS: Ultrasound spectrums of lymph nodes during EBUS-TBNA were retrospectively analyzed. A linear regression of frequency spectrum and the ultrasonic spectral parameters midband-fit, slope, and intercept were calculated. Mean values for these parameters within lymph nodes were computed. The cutoff values for each parameter for distinguishing metastatic vs benign lymph nodes were first determined within the training set; these cutoff values were then applied to the testing set for validation. RESULTS: Overall, 362 lymph nodes (112 metastatic, 250 benign) were analyzed as the training set, and 284 lymph nodes (74 metastatic, 210 benign) were evaluated as the testing set. In the training set, all of the parameters showed a significant difference between metastatic and benign lymph nodes (P < .001). The metastatic nodes tended to show low midband fit, high slope, and low intercept. When midband-fit and intercept were combined, the diagnostic accuracy was maximized in the training set. In the testing set, the combination of intercept and slope produced the highest diagnostic accuracy, with the following outcomes: sensitivity, 79.7%; specificity, 84.3%; diagnostic accuracy, 83.1%; positive predictive value, 64.1%; and negative predictive value, 92.2%. CONCLUSIONS: Metastatic lymph nodes possess unique ultrasonic spectrum features, and spectrum analysis can be used as a novel diagnostic tool for differentiating between benign and malignant nodes in patients with lung cancer. PMID- 26836933 TI - Sex-Specific Prediction Models for Sleep Apnea From the Hispanic Community Health Study/Study of Latinos. AB - OBJECTIVE: We developed and validated the first-ever sleep apnea (SA) risk calculator in a large population-based cohort of Hispanic/Latino subjects. METHODS: Cross-sectional data on adults from the Hispanic Community Health Study/Study of Latinos (2008-2011) were analyzed. Subjective and objective sleep measurements were obtained. Clinically significant SA was defined as an apnea hypopnea index >= 15 events per hour. Using logistic regression, four prediction models were created: three sex-specific models (female-only, male-only, and a sex * covariate interaction model to allow differential predictor effects), and one overall model with sex included as a main effect only. Models underwent 10-fold cross-validation and were assessed by using the C statistic. SA and its predictive variables; a total of 17 variables were considered. RESULTS: A total of 12,158 participants had complete sleep data available; 7,363 (61%) were women. The population-weighted prevalence of SA (apnea-hypopnea index >= 15 events per hour) was 6.1% in female subjects and 13.5% in male subjects. Male-only (C statistic, 0.808) and female-only (C statistic, 0.836) prediction models had the same predictor variables (ie, age, BMI, self-reported snoring). The sex interaction model (C statistic, 0.836) contained sex, age, age * sex, BMI, BMI * sex, and self-reported snoring. The final overall model (C statistic, 0.832) contained age, BMI, snoring, and sex. We developed two websites for our SA risk calculator: one in English (https://www.montefiore.org/sleepapneariskcalc.html) and another in Spanish (http://www.montefiore.org/sleepapneariskcalc-es.html). CONCLUSIONS: We created an internally validated, highly discriminating, well calibrated, and parsimonious prediction model for SA. Contrary to the study hypothesis, the variables did not have different predictive magnitudes in male and female subjects. PMID- 26836935 TI - A Randomized Controlled Trial of a Novel Sheath Cryoprobe for Bronchoscopic Lung Biopsy in a Porcine Model. AB - BACKGROUND: Transbronchial forceps biopsy (FBx) has been the preferred method for obtaining bronchoscopic lung biopsy specimens. Cryoprobe biopsy (CBx) has been shown to obtain larger and higher quality samples, but is limited by its inability to retrieve the sample through the working channel of the bronchoscope, requiring the bronchoscope to leave the airway for sample retrieval. OBJECTIVE: We evaluated a novel device using a sheath cryobiopsy (SCBx). This method allows for specimen retrieval through the working channel of the bronchoscope, with the scope remaining inside the airway. METHODS: This prospective, randomized controlled, single-blinded porcine study compared a 1.1-mm SCBx probe, a 1.9-mm CBx probe, and 2.0-mm FBx forceps. Assessment of histologic accessibility, sample quantity and quality, number of attempts to acquire and retrieve samples, cryoprobe activation time, fluoroscopy activation time, technical feasibility, and complications were compared. RESULTS: Samples adequate for standard pathologic processing were retrieved with 82.1% of the SCBx specimens, 82.9%% of the CBx specimens, and 30% of the FBx specimens. The histologic accessibility of both SCBx (P = .0002) and CBx (P = .0003) was superior to FBx. Procedure time for FBx was faster than for both SCBx and CBx, but SCBx was significantly faster than CBx (P < .0001). Fluoroscopy time was lower for both SCBx and CBx compared with FBx. There were no significant bleeding events. CONCLUSIONS: SCBx is a feasible technique providing a higher quality lung biopsy specimen compared with FBx and can successfully be retrieved through the working channel. Human studies are needed to further assess this technique with additional safety data. PMID- 26836934 TI - Association Between Occupational Exposures and Sarcoidosis: An Analysis From Death Certificates in the United States, 1988-1999. AB - BACKGROUND: Sarcoidosis is a disease that is associated with occupational and environmental antigens, in the setting of a susceptible host. The aim of this study was to examine the association between sarcoidosis mortality and previously reported occupational exposures based on sex and race. METHODS: The decedents enrolled in this study were derived from United States death certificates from 1988-1999. Cause of death was coded according to ICD-9 and ICD-10. The usual occupation was coded with Bureau of the Census Occupation Codes. Mortality odds ratio (MOR) were determined and multiple Poisson regression were performed to evaluate the independent exposure effects after adjustment for age, sex, race and other occupational exposures. RESULTS: Of the 7,118,535 decedents in our study, 3,393 were identified as sarcoidosis-related, including 1,579 identified as sarcoidosis being the underlying cause of death. The sarcoidosis-related MOR of any occupational exposure was 1.52 (95% CI, 1.35-1.71). Women with any exposure demonstrated an increased MOR compared to women without (MOR 1.65, 95% CI, 1.45 1.89). The mortality risk was significantly elevated in those with employment involving metal working, health care, teaching, sales, banking, and administration. Higher sarcoidosis-related mortality risks associated with specific exposures were noted in women vs men and blacks vs whites. CONCLUSIONS: Findings of prior occupations and risk of sarcoidosis were verified using sarcoidosis mortality rates. There were significant differences in risk for sarcoidosis mortality by occupational exposures based on sex and race. PMID- 26836936 TI - NADPH Oxidase-4 Overexpression Is Associated With Epithelial Ciliary Dysfunction in Neutrophilic Asthma. AB - BACKGROUND: Bronchial epithelial ciliary dysfunction is an important feature of asthma. We sought to determine the role in asthma of neutrophilic inflammation and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases in ciliary dysfunction. METHODS: Bronchial epithelial ciliary function was assessed by using video microscopy in fresh ex vivo epithelial strips from patients with asthma stratified according to their sputum cell differentials and in culture specimens from healthy control subjects and patients with asthma. Bronchial epithelial oxidative damage was determined by 8-oxo-dG expression. Nicotinamide adenine dinucleotide phosphate oxidase (NOX)/dual oxidase (DUOX) expression was assessed in bronchial epithelial cells by using microarrays, with NOX4 and DUOX1/2 expression assessed in bronchial biopsy specimens. Ciliary dysfunction following NADPH oxidase inhibition, using GKT137831, was evaluated in fresh epithelial strips from patients with asthma and a murine model of ovalbumin sensitization and challenge. RESULTS: Ciliary beat frequency was impaired in patients with asthma with sputum neutrophilia (n = 11) vs those without (n = 10) (5.8 [0.6] Hz vs 8.8 [0.5] Hz; P = .003) and was correlated with sputum neutrophil count (r = 0.70; P < .001). Primary bronchial epithelial cells expressed DUOX1/2 and NOX4. Levels of 8-oxo-dG and NOX4 were elevated in patients with neutrophilic vs nonneutrophilic asthma, DUOX1 was elevated in both, and DUOX2 was elevated in nonneutrophilic asthma in vivo. In primary epithelial cultures, ciliary dysfunction did not persist, although NOX4 expression and reactive oxygen species generation was increased from patients with neutrophilic asthma. GKT137831 both improved ciliary function in ex vivo epithelial strips (n = 13), relative to the intensity of neutrophilic inflammation, and abolished ciliary dysfunction in the murine asthma model with no reduction in inflammation. CONCLUSIONS: Ciliary dysfunction is increased in neutrophilic asthma associated with increased NOX4 expression and is attenuated by NADPH oxidase inhibition. PMID- 26836938 TI - Long-term Course of Depression Trajectories in Patients With COPD: A 3-Year Follow-up Analysis of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints Cohort. AB - BACKGROUND: There is insufficient evidence about the long-term course of depressive symptom trajectories and their impact among patients with COPD. METHODS: We analysed 3-year data obtained from patients with COPD participating in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study. Patients were split into four groups on the basis of Center for Epidemiologic Studies Depression Scale score (< 16 vs >= 16) and antidepressant use (yes vs no) at baseline and at 3 years: never depressed, new onset, remittent, and persistent depression. Baseline characteristics were used to assess factors associated with the group by using logistic regression. RESULTS: A total of 1,589 patients with COPD completed the 3-year follow-up. Of these, 55% (n = 869) were classified as never depressed, 24% (n = 377) were classified as persistently depressed, 14% (n = 226) developed new onset of depression, and 7% (n = 117) had depression that remitted. Female sex and history of stroke were associated with substantial increases in the odds of persistent depression (OR, 2.95; 95% CI, 2.05-4.24 and OR, 3.09; 95% CI, 1.43-6.67, respectively). Odds of new onset depression increased with worse health status (OR, 1.10; 95% CI, 1.04 1.17 per 4-point increase in St. George's Respiratory Questionnaire score) and moderate to severe dyspnea (OR, 1.57; 95% CI, 1.07-2.31 for modified Medical Research Council score >= 2 vs 0 or 1). During follow-up, patients with persistent or new-onset depression experienced more exacerbations and more pronounced loss in performance as assessed by reduction in the 6-min walk distance (6MWD) test score. CONCLUSIONS: About one in four patients with COPD had persistent depressive symptoms over 3 years. Clinicians should be aware of the characteristics of persistent and new onset depressive symptoms, which are associated with risk of exacerbations and loss of performance on the 6MWD test. Interventions that ameliorate the course of depression are needed. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00292552; URL: www.clinicaltrials.gov. PMID- 26836937 TI - Risk of Procedural Hemorrhage. AB - Patients who are critically ill and hospitalized often require invasive procedures as a part of their medical care. Each procedure carries a unique set of risks and associated complications, but common to all of them is the risk of hemorrhage. Central venous catheterization, arterial catheterization, paracentesis, thoracentesis, tube thoracostomy, and lumbar puncture constitute a majority of the procedures performed in patients who are hospitalized. In this article, the authors will discuss the risk factors for bleeding complications from each of these procedures and methods to minimize risk. Physicians often correct coagulopathy prior to procedures to decrease bleeding risk, but there is minimal evidence to support this practice. PMID- 26836939 TI - Airway-Centered Fibroelastosis: A Distinct Entity. AB - OBJECTIVE: To describe a new entity characterized by airway-centered fibroelastosis. METHODS: We identified cases with prominent airway-centered elastosis in lung samples, and little or no pleural involvement identified through a pathologic database at a single institution over an 8-year period. RESULTS: Airway-centered fibroelastosis was characterized by (1) extensive airway centered fibroelastosis of the upper lobes on histopathology and (2) marked bronchial abnormalities with bronchial wall thickening, bronchial wall deformation, and bronchiectasis, along with progressive parenchymal retraction and predominantly subpleural upper-lobe consolidations on high-resolution CT. Pateints were five nonsmoking women aged between 38 and 56 years old. They experienced chronic dyspnea with acute attacks of wheezing and dyspnea. Moderate to severe physiological abnormalities were observed, with an obstructive pattern in three cases and a restriction in two. Despite inhaled and oral corticosteroids, the disease was progressive in all patients and evolved to chronic respiratory failure, requiring lung transplantation in two patients. Four patients had chronic asthma. CONCLUSIONS: We consider airway-centered fibroelastosis to be a unique and distinct pathological entity in women that needs to be individualized, with a specific clinical, imaging, and pathological presentation. We hypothesize that airway-centered fibroelastosis may be idiopathic or asthma-associated. PMID- 26836940 TI - Patients With Fibrotic Interstitial Lung Disease Hospitalized for Acute Respiratory Worsening: A Large Cohort Analysis. AB - BACKGROUND: Acute respiratory worsening (ARW) requiring hospitalization in patients with fibrotic interstitial lung disease (f-ILD) is common. Little is known about the frequency and implications of ARW in IPF and non-IPF ILD patients hospitalized for acute exacerbation (AE) vs known causes of ARW. METHODS: All consecutive patients with f-ILD hospitalized with ARW at our institution from 2000 to 2014 were reviewed. ARW was defined as any worsening of respiratory symptoms with new or worsened hypoxemia or hypercapnia within 30 days of admission. Suspected AE was defined using modified 2007 American Thoracic Society/European Respiratory Society criteria. Known causes of ARW were reviewed and collated along with in-hospital and all-cause mortality postdischarge. RESULTS: A total of 220 patients (100 with IPF and 120 non-IPF) composed 311 admissions for ARW. Suspected AE (SAE) comprised 52% of ARW admissions, followed by infection (20%), and subacute progression of disease (15%). In-hospital mortality was similar in patients with IPF vs patients without (55 vs 45%, P = .18), but worse in suspected AE admission types (OR, 3.1 [1.9-5.14]). One-year survival after last ARW admission for the whole cohort was 22%, despite only 27% of patients presenting with baseline oxygen requirement at admission and a mean admission Charlson Comorbidity Index score of 5.4 (expected 1-year survival, 89%). Survival after discharge was similar between SAE and secondary ARW admission types in both IPF and non-IPF patients. CONCLUSIONS: Among patients with f-ILD, hospitalization for ARW appears associated with significant in hospital and postdischarge mortality regardless of underlying fibrotic lung disease or non-AE cause of acute respiratory decline. PMID- 26836941 TI - Developing an Interventional Pulmonary Service in a Community-Based Private Practice: A Case Study. AB - Interventional pulmonology (IP) is a field that uses minimally invasive techniques to diagnose, treat, and palliate advanced lung disease. Technology, formal training, and reimbursement for IP procedures have been slow to catch up with other interventional subspecialty areas. A byproduct of this pattern has been limited IP integration in private practice settings. We describe the key aspects and programmatic challenges of building an IP program in a community based setting. A philosophical and financial buy-in by stakeholders and a regionalization of services, within and external to a larger practice, are crucial to success. Our experience demonstrates that a successful launch of an IP program increases overall visits as well as procedural volume without cannibalizing existing practice volume. We hope this might encourage others to provide this valuable service to their own communities. PMID- 26836942 TI - Lung Ultrasonography to Diagnose Transient Tachypnea of the Newborn. AB - BACKGROUND: This study explored the sensitivity and specificity of ultrasound for diagnosing transient tachypnea of the newborn (TTN). METHODS: Ultrasound was performed by one export. Patients were placed in a supine, lateral recumbent, or prone position. The probe was placed perpendicular or parallel to the ribs, and each region of the lung was scanned. The scan results were compared with conventional chest radiographic results. RESULTS: A total of 1,358 infants were included in this study. We identified 412 cases without pulmonary diseases, 228 TTN cases, 358 respiratory distress syndrome (RDS) cases, 85 meconium aspiration syndrome (MAS) cases, 215 infectious pneumonia cases, and 60 other cases. The primary ultrasonic characteristic of TTN was pulmonary edema. "White lung" or a "compact B-line" were only observed in severe cases, whereas TTN primarily presented as pulmonary interstitial syndrome or "double lung point." Furthermore, double lung point could appear during the recovery period of severe TTN or RDS, MAS, and pneumonia. Lung consolidation with air bronchograms was not observed in TTN patients. The results showed that white lung or a compact B-line exhibited a sensitivity of 33.8% and a specificity of 91.3% in diagnosing TTN, whereas double lung point exhibited a sensitivity of 45.6% and a specificity of 94.8% in diagnosing severe TTN. CONCLUSIONS: Pulmonary edema, alveolar-interstitial syndrome, double lung point, white lung, and compact B-line are the primary ultrasound characteristics of TTN. Ultrasonic diagnosis of TTN based on these findings is accurate and reliable. TTN can be ruled out in the presence of lung consolidation with air bronchograms. PMID- 26836943 TI - Prevalence, Molecular Characterization, and Antimicrobial Susceptibility of Methicillin-Resistant Staphylococcus aureus Isolated from Milk and Dairy Products. AB - The present work was undertaken to study the prevalence, molecular characterization, virulence factors, and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) in raw milk and dairy products in Mansoura City, Egypt. MRSA was detected in 53% (106/200) among all milk and dairy products with prevalence rates of 75%, 65%, 40%, 50%, and 35% in raw milk, Damietta cheese, Kareish cheese, ice cream, and yogurt samples, respectively. The mean S. aureus counts were 3.49, 3.71, 2.93, 3.40, and 3.23 log10 colony-forming units (CFU)/g among tested raw milk, Damietta cheese, Kareish cheese, ice cream and yogurt, respectively, with an overall count of 3.41 log10 CFU/g. Interestingly, all recovered S. aureus isolates were genetically verified as MRSA strains by molecular detection of the mecA gene. Furthermore, genes encoding alpha-hemolysin (hla) and staphylococcal enterotoxins (sea, seb, sec) were detected in all isolates. The antimicrobial susceptibility pattern of recovered MRSA isolates against 13 tested antimicrobials revealed that the least effective drugs were penicillin G, cloxacillin, tetracycline, and amoxicillin with bacterial resistance percentages of 87.9%, 75.9%, 65.2%, and 55.6%, respectively. These findings suggested that milk and dairy products represent a potential infection risk threat of multidrug-resistant and toxigenic S. aureus in Egypt due to neglected hygienic practices during production, retail, or storage stages. These findings highlighted the crucial importance of applying more restrictive hygienic measures in dairy production in Egypt for food safety. PMID- 26836945 TI - Reply to 'Concerns about 2015 ERC Guidelines on pre-hospital use of ADP-receptor antagonists in patients with STEMI (ACS 335)'. PMID- 26836944 TI - Association of early withdrawal of life-sustaining therapy for perceived neurological prognosis with mortality after cardiac arrest. AB - BACKGROUND: Withdrawing life-sustaining therapy because of perceived poor neurological prognosis (WLST-N) is a common cause of hospital death after out-of hospital cardiac arrest (OHCA). Although current guidelines recommend against WLST-N before 72h (WLST-N<72), this practice is common and may increase mortality. We sought to quantify these effects. METHODS: In a secondary analysis of a multicenter OHCA trial, we evaluated survival to hospital discharge and survival with favorable functional status (modified Rankin Score <=3) in adults alive >1h after hospital admission. Propensity score modeling the probability of exposure to WLST-N<72 based on pre-exposure covariates was used to match unexposed subjects with those exposed to WLST-N<72. We determined the probability of survival and functionally favorable survival in the unexposed matched cohort, fit adjusted logistic regression models to predict outcomes in this group, and then used these models to predict outcomes in the exposed cohort. Combining these findings with current epidemiologic statistics we estimated mortality nationally that is associated with WLST-N<72. RESULTS: Of 16,875 OHCA subjects, 4265 (25%) met inclusion criteria. WLST-N<72 occurred in one-third of subjects who died in hospital. Adjusted analyses predicted that exposed subjects would have 26% survival and 16% functionally favorable survival if WLST-N<72 did not occur. Extrapolated nationally, WLST-N<72 may be associated with mortality in approximately 2300 Americans each year of whom nearly 1500 (64%) might have had functional recovery. CONCLUSIONS: After OHCA, death following WLST-N<72 may be common and is potentially avoidable. Reducing WLST-N<72 has national public health implications and may afford an opportunity to decrease mortality after OHCA. PMID- 26836946 TI - Extracorporeal resuscitation for refractory out-of-hospital cardiac arrest in adults: A systematic review of international practices and outcomes. AB - AIM: Extracorporeal resuscitation during cardiopulmonary resuscitation (ECPR) deploys rapid cardiopulmonary bypass to sustain oxygenated circulation until the return of spontaneous circulation (ROSC). The purpose of this systematic review is to address the defining elements and outcomes (quality survival and organ donation) of currently active protocols for ECPR in refractory out-of-hospital cardiac arrest (OHCA) of cardiac origin in adult patients. The results may inform policy and practices for ECPR and help clarify the corrresponding intersection with deceased organ donation. METHODS: We searched Medline, Embase, Cochrane and seven other electronic databases from 2005 to 2015, with no language restrictions. Internal validity and the quality of the studies reporting outcomes and guidelines were assessed. The review was included in the international prospective register of systematic reviews (Prospero, CRD42014015259). RESULTS: One guideline and 20 outcome studies were analyzed. Half of the studies were prospective observational studies assessed to be of fair to good methodological quality. The remainder were retrospective cohorts, case series, and case studies. Ages ranged from 16 to 75 years and initial shockable cardiac rhythms, witnessed events, and a reversible primary cause of cardiac arrest were considered favorable prognostic factors. CPR duration and time to hospital cannulation varied considerably. Coronary revascularization, hemodynamic interventions and targeted temperature management neuroprotection were variable. A total of 833 patients receiving this ECPR approach had an overall reported survival rate of 22%, including 13% with good neurological recovery. Additionally, 88 potential and 17 actual deceased organ donors were identified among the non-survivor population in 8 out of 20 included studies. Study heterogeneity precluded a meta analysis preventing any meaningful comparison between protocols, interventions and outcomes. CONCLUSIONS: ECPR is feasible for refractory OHCA of cardiac origin in adult patients. It may enable neurologically good survival in selected patients, who practically have no other alternative in order to save their lives with quality of life, and contribute to organ donation in those who die. Large, prospective studies are required to clarify patient selection, modifiable outcome variables, risk-benefit and cost-effectiveness. PMID- 26836947 TI - Synthetic Study of Rubriflordilactone B: Highly Stereoselective Construction of the C-5-epi ABCDE Ring System. AB - A highly stereocontrolled construction of the C-5-epi ABCDE-ring system of rubriflordilactone B has been developed. The present synthesis features a convergent strategy to construct the C-5-epi AB-ring utilizing Mukaiyama-Michael reaction and forge the CDE ring in one step using intramolecular [2 + 2 + 2] cycloaddition of triynes. PMID- 26836948 TI - Correction to Antiproliferative Trihydroxyalkylcyclohexenones from Pleiogynium timoriense. PMID- 26836949 TI - The role of IL-18 in type 1 diabetic nephropathy: The problem and future treatment. AB - Diabetic vascular complication is a leading cause of diabetic nephropathy, a progressive increase in urinary albumin excretion coupled with elevated blood pressure leading to declined glomerular filtration and eventually end stage renal failure. There is growing evidence that activated inflammation is contributing factor to the pathogenesis of diabetic nephropathy. Meanwhile, IL-18, a member of the IL-1 family of inflammatory cytokines, is involved in the development and progression of diabetic nephropathy. However, the benefits derived from the current therapeutics for diabetic nephropathy strategies still provide imperfect protection against renal progression. This imperfection points to the need for newer therapeutic agents that have potential to affect primary mechanisms contributing to the pathogenesis of diabetic nephropathy. Therefore, the recognition of IL-18 as significant pathogenic mediators in diabetic nephropathy leaves open the possibility of new potential therapeutic targets. PMID- 26836950 TI - Phase II multicentre trial of oral quisinostat, a histone deacetylase inhibitor, in patients with previously treated stage IB-IVA mycosis fungoides/Sezary syndrome. AB - BACKGROUND: Quisinostat is a hydroxamate, second-generation, orally available pan histone deacetylase inhibitor. OBJECTIVES: To evaluate the efficacy and safety of oral quisinostat in patients with previously treated cutaneous T-cell lymphoma (CTCL). METHODS: Patients received quisinostat 8 mg or 12 mg on days 1, 3 and 5 of each week in 21-day treatment cycles. Primary efficacy end point was cutaneous response rate (RR) based on the modified Severity Weighted Assessment Tool (mSWAT). Secondary end points included global RR, duration of response (DOR) in skin, progression-free survival (PFS), pruritus relief, safety and pharmacodynamic markers. RESULTS: Eight of 26 (25 evaluable) patients achieved >= 50% reduction in mSWAT score at least once, with confirmed cutaneous response in six (RR 24%). There was a low global RR of 8%. DOR in skin ranged from 2.8 to 6.9 months. Median PFS was 5.1 months. Pruritus relief was more frequent in cutaneous responders (67%) than nonresponders (32%). Serial tumour biopsies revealed an increase in acetylated tubulin, indicating a target effect of histone deacetylase 6. Twenty-one of 26 (81%) patients were withdrawn from the study before or at clinical cut-off; five (19%) continued to receive treatment with quisinostat. The most common drug-related adverse events were nausea, diarrhoea, asthenia, hypertension, thrombocytopenia and vomiting. Grade 3 drug-related adverse events included hypertension, lethargy, pruritus, chills, hyperkalaemia and pyrexia. CONCLUSIONS: Quisinostat 12 mg three times weekly is active in the treatment of patients with relapsed or refractory CTCL, with an acceptable safety profile. Combination therapy with other drugs active in CTCL may be appropriate. PMID- 26836951 TI - Self-Care and Mobility Following Postacute Rehabilitation for Older Adults With Hip Fracture: A Multilevel Analysis. AB - OBJECTIVE: To examine contextual (facility and community) and individual factors associated with self-care and mobility outcomes among Medicare hip fracture patients receiving inpatient rehabilitation. DESIGN: Retrospective cohort study of 3 linked data files: Inpatient Rehabilitation Facility-Patient Assessment Instrument, Provider of Services, and Area Health Resources. Multilevel modeling was used to examine the effects of contextual and individual factors on self-care and mobility outcomes. SETTING: Inpatient rehabilitation facilities (IRFs). PARTICIPANTS: Medicare hip fracture patients (N=35,264; mean age, 81y) treated in IRFs (N=1072) in 2012. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Self care (eating, grooming, bathing, upper and lower body dressing, toileting) and mobility (walk/wheelchair, stairs) at discharge. RESULTS: Mean +/- SD self-care and mobility scores at admission were 3.17+/-.87 and 1.24+/-.51, respectively; mean +/- SD self-care and mobility scores at discharge were 5.03+/-1.09 and 3.31+/-1.54, respectively. Individual and contextual levels explained 44.4% and 21.6% of the variance in self-care at discharge, respectively, and 19.5% and 1.9% of the variance in mobility at discharge, respectively. At the individual level, age, race/ethnicity, cognitive and motor FIM scores at admission, and tier comorbidities explained variance in self-care and mobility; sex and length of stay explained variance only in self-care. At the contextual level, facilities' case mix (mean patient age, percent non-Hispanic white, mean self-care score at admission) and structural characteristics (rural location, freestanding, for profit ownership) explained variance only in self-care; facilities' case mix (mean patient age, percent non-Hispanic white, percent living with social support, mean mobility score at admission) explained variance in mobility. Community variables were nonsignificant. CONCLUSIONS: Individual and facility factors were significant predictors of discharge self-care and mobility among Medicare hip fracture patients in IRFs. The findings may improve quality of IRF services to hip fracture patients and inform risk adjustment methods. PMID- 26836953 TI - Self-Reported Cognitive Concerns in People With Lower Limb Loss. AB - OBJECTIVES: To investigate differences between self-reported cognitive concerns in people with lower limb loss (LLL) and normative data derived from the U.S. general population, and secondarily to determine whether there were cognitive differences based on amputation etiology or age. DESIGN: Survey. SETTING: General community. PARTICIPANTS: A volunteer sample of persons with LLL (N=1086) resulting from trauma or dysvascular complications who regularly use a prosthetic limb. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The Quality of Life in Neurological Disorders Applied Cognition-General Concerns Short Form version 1.0 (Neuro-QoL ACGC), an 8-item self-report measure of general cognitive concerns. RESULTS: People with LLL reported significantly more cognitive concerns than the Quality of Life in Neurological Disorders normative sample. Mean Neuro-QoL ACGC scores were significantly lower than normative values (P<.001) across subgroups defined by age (ie, <40, 40-49, 50-59, 60-69, and 70+ years) and subgroups defined by etiology (ie, traumatic and dysvascular LLL). However, there were no significant differences in cognitive concerns among age subgroups (P=.84) or between the etiology subgroups (P=.58). CONCLUSIONS: When compared with the Quality of Life in Neurological Disorders normative sample, individuals with LLL report greater concerns with cognitive health. Cognitive concerns were not differentially affected by age or cause of amputation. The presence of cognitive concerns in people with LLL suggests a need to assess perceived cognitive function in order to tailor education and training in prosthetic use and care. PMID- 26836954 TI - Reliability and Validity of Ratings of Perceived Exertion in Persons With Multiple Sclerosis. AB - OBJECTIVE: To test the reliability and validity of using the Borg rating of perceived exertion (RPE) scale (ratings 6-20) in persons with multiple sclerosis (PwMS). DESIGN: Nonrandomized repeated measures. SETTING: Research laboratory. PARTICIPANTS: Volunteer sample (N=27) comprised of 16 PwMS (10 women) and 11 age matched persons without multiple sclerosis (MS) (6 women). Clinical measures included symptomatic fatigue, depression, and MS functional capacity. INTERVENTIONS: A submaximal cycling test was performed to estimate maximal capacity. Participants then pedaled for 2 minutes at 50% and 60% of predicted maximal oxygen consumption per unit time (Vo2), and physiological measures and RPE were obtained (week 1: response protocol). One week later, participants replicated the prescribed Vo2 using the RPE range from week 1 (week 2: reproduction protocol). Vo2, heart rate, and respiratory quotient were measured continuously; RPE and workload were measured every minute; and blood lactate and mean arterial pressure were measured after exercise. MAIN OUTCOME MEASURES: RPE, workload, Vo2, and heart rate from week 1 to week 2. RESULTS: PwMS had greater fatigue (P<.01) and disability (P<.001). Baseline measures were similar between groups and weeks. During exercise, RPE, workload, Vo2, and heart rate were similar between groups. Both groups had an intraclass correlation coefficient >.86 for RPE, workload, and Vo2. The intraclass correlation coefficient was comparatively lower for heart rate for both groups (MS group: .72, non-MS group: .83). RPE was highly correlated with Vo2 (r=.691, P<.001) and workload (r=.700, P<.001) for the MS group. CONCLUSIONS: Results suggest that RPE can be reliably reproduced, is valid, and may be used in exercise prescription in mildly to moderately impaired PwMS during cycling exercise. PMID- 26836952 TI - Sex-Specific Predictors of Inpatient Rehabilitation Outcomes After Traumatic Brain Injury. AB - OBJECTIVE: To identify sex-specific predictors of inpatient rehabilitation outcomes among patients with a traumatic brain injury (TBI) from a population based perspective. DESIGN: Retrospective cohort study. SETTING: Inpatient rehabilitation. PARTICIPANTS: Patients in inpatient rehabilitation for a TBI within 1 year of acute care discharge between 2008/2009 and 2011/2012 (N=1730, 70% men, 30% women). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Inpatient rehabilitation length of stay, total FIM score, and motor and cognitive FIM ratings at discharge. RESULTS: Sex, as a covariate in multivariable linear regression models, was not a significant predictor of rehabilitation outcomes. Although many of the predictors examined were similar across men and women, sex specific multivariable models identified some predictors of rehabilitation outcome that are specific for men and women; mechanism of injury (P<.0001) was a significant predictor of functional outcome only among women, whereas comorbidities (P<.0001) was a significant predictor for men only. CONCLUSIONS: Predictors of outcomes after inpatient rehabilitation differed by sex, providing evidence for a sex-specific approach in planning and resource allocation for inpatient rehabilitation services for patients with TBI. PMID- 26836955 TI - Danish reading span data from 283 hearing-aid users, including a sub-group analysis of their relationship to speech-in-noise performance. AB - OBJECTIVE: This study provides descriptive statistics of the Danish reading span (RS) test for hearing-impaired adults. The combined effect of hearing loss, RS score, and age on speech-in-noise performance in different spatial settings was evaluated in a subset of participants. DESIGN: Data from published and unpublished studies were re-analysed. Data regarding speech-in-noise performance with co-located or spatially separated sound sources were available for a subset of participants. STUDY SAMPLE: RS scores from 283 hearing-impaired participants were extracted from past studies, and 239 of these participants had completed a speech-in-noise test. RESULTS: RS scores (mean = 41.91%, standard deviation = 11.29%) were related to age (p <0.01), but not pure-tone average (PTA) (p = 0.29). Speech-in-noise performance for co-located sound sources was related to PTA and RS score (both p < 0.01, adjusted R-squared = 0.226). Performance for spatially separated sounds was related to PTA (p < 0.01, adjusted R-squared = 0.10) but not RS score (p = 0.484). We found no differences between the standardized coefficients of the two regression models. CONCLUSIONS: The distribution of RS scores indicated a high test difficulty. We found that age should be controlled when RS scores are compared across populations. The experimental setup of the speech-in-noise test may influence the relationship between performance and RS score. PMID- 26836956 TI - Type-I superconductivity in KBi2 single crystals. AB - We report on the detailed transport, magnetic, thermodynamic properties and theoretical calculation of KBi2 single crystals in superconducting and normal states. KBi2 exhibits metallic behavior at a normal state and enters the superconducting state below T(c) = 3.573 K. Moreover, KBi2 exhibits low critical fields in all measurements, field-induced crossover from second- to first-order phase transition in specific heat measurements, the typical magnetization isotherms of type-I superconductors, and a small Ginzburg-Landau parameter kappa(GL) = 0.611. These results clearly indicate that KBi2 is a type-I superconductor with a thermodynamic critical field H(c) = 234.3(3) Oe. PMID- 26836957 TI - Superior performance of co-cultured mesenchymal stem cells and hepatocytes in poly(lactic acid-glycolic acid) scaffolds for the treatment of acute liver failure. AB - Recently, cell-based therapies have attracted attention as promising treatments for acute liver failure (ALF). Bone marrow-derived mesenchymal stem cells (MSCs) are potential candidates for co-culture with hepatocytes in poly(lactic acid glycolic acid) (PLGA) scaffolds to support hepatocellular function. However, the mechanism of culturing protocol using PLGA scaffolds for MSC differentiation into hepatocyte-like cells as well as the therapeutic effect of cell seeded PLGA scaffolds on ALF remain unsatisfactory in clinical application. Here, MSCs and hepatocytes were co-cultured at ratios of 1:2.5 (MSCs: Hep), 1:5 and 1:10, respectively. The proliferation abilities of these co-cultured cells were detected by CCK8, MTT, EdU and by scanning electron microscopy (SEM), and the ability of MSCs to differentiate into hepatocytes was detected by PCR, western blot and immunofluorescence staining. Therapeutic trials of cell seeded PLGA scaffolds were conducted through mouse abdominal cavity transplantation. Results showed that the 1:5 group showed significantly higher cellular proliferation than the 1:2.5 and 1:10 groups, supernatant albumin and urea nitrogen levels were also significantly higher in the 1:5 group than in other two groups. Similarly, the 1:5 group demonstrated better DNA transcription and liver-specific protein (albumin, CK18 and P450) production. Meanwhile, the GalN-stimulated levels of ALT, AST and TBil in mouse serum were down-regulated significantly more by (MSC + Hep)-PLGA scaffold treatment than MSC-PLGA or Hep-PLGA scaffold treatments. Furthermore, the (MSC + Hep)-PLGA scaffold-treated ALF mice showed a lower immunogenic response level than the other two groups. These data suggested that the ratio of 1:5 (MSC:Hep) co-cultures was the optimal ratio for MSCs to support hepatocellular metabolism and function in PLGA scaffolds in vitro, the (MSC + Hep)-PLGA scaffold treatment could perform better restoration for damaged liver function and could give ALF mice a greater survival rate than the monocell seeded PLGA scaffold treatment. PMID- 26836958 TI - Undiagnosed Chronic Obstructive Pulmonary Disease Contributes to the Burden of Health Care Use. Data from the CanCOLD Study. AB - RATIONALE: Chronic obstructive pulmonary disease (COPD) remains undiagnosed in many individuals with persistent airflow limitation. These individuals may be susceptible to exacerbation-like respiratory events that consume health care resources. OBJECTIVES: To compare exacerbation-like respiratory events, event prevalence, and differences in the odds of using medication and/or health services between subjects with diagnosed and undiagnosed COPD. METHODS: Subjects sampled from the general population participating in the CanCOLD (Canadian Cohort Obstructive Lung Disease) study, with at least 12 months of exacerbation-event follow-up who were classified as having physician-diagnosed or undiagnosed COPD were assessed. Exacerbation-like respiratory events were captured using a questionnaire administered every 3 months. MEASUREMENTS AND MAIN RESULTS: A total of 355 subjects were undiagnosed and 150 were diagnosed with COPD. Undiagnosed subjects were less symptomatic and functionally impaired, had been prescribed fewer respiratory medications, and had better health status. The incidence of reported exacerbation-like events was higher in diagnosed subjects and increased in both groups with the severity of airflow obstruction. Although subjects with diagnosed COPD were more often prescribed medication for exacerbation events, health service use for exacerbation events was similar in both groups. CONCLUSIONS: Most subjects with COPD in Canada remain undiagnosed. These subjects are less symptomatic and impaired, which may partly explain lack of diagnosis. Although patients with undiagnosed COPD experience fewer exacerbations than those with diagnosed COPD, they use a similar amount of health services for exacerbation events; thus, the overall health system burden of exacerbations in those with undiagnosed COPD is considerable. PMID- 26836959 TI - Influence of different types of coals and stoves on the emissions of parent and oxygenated PAHs from residential coal combustion in China. AB - To evaluate the influence of coal property and stove efficiency on the emissions of parent polycyclic aromatic hydrocarbons (pPAHs) and oxygenated PAHs (oPAHs) during the combustion, fifteen coal/stove combinations were tested in this study, including five coals of different geological maturities in briquette and chunk forms burned in two residential stoves. The emission factors (EFs) of pPAHs and oPAHs were in the range of 0.129-16.7 mg/kg and 0.059-0.882 mg/kg, respectively. The geological maturity of coal significantly affected the emissions of pPAHs and oPAHs with the lower maturity coals yielding the higher emissions. The chunk-to briquette transformation of coal dramatically increased the emissions of pPAHs and oPAHs during the combustion of anthracite, whereas this transformation only elevated the emissions of high molecular weight PAHs for bituminous coals. The influence of stove type on the emissions of pPAHs and oPAHs was also geological maturity-dependent. High efficiency stove significantly reduced the emissions of PAHs from those relatively high-maturity coals, but its influences on low maturity coals were inconstant. PMID- 26836960 TI - Father's Role in Breastfeeding Promotion: Lessons from a Quasi-Experimental Trial in China. AB - AIMS: The aims of this study were to evaluate the effectiveness of an educational intervention involving fathers on breastfeeding initiation and exclusive breastfeeding rate, and to explore mothers' perceptions of their partners' support of breastfeeding. MATERIALS AND METHODS: This study was a quasi experimental pretest-posttest design with two groups. A convenience sample consisting of 72 expectant mothers was recruited. Thirty-six women with their partners were assigned to the intervention group, and 36 women alone were in the control group. Both groups were offered similar education contents, and the intervention group was given additional information on how fathers could support their partners, both emotionally and physically, during the breastfeeding process. Student's t test, chi-square test, and Mann-Whitney U test were used to detect group differences. RESULTS: The prevalence rates of exclusive breastfeeding at 4 months and 6 months of the intervention group were significantly higher than there were in the control group (51.4% and 26.4%, p = 0.034; 40.0% and 17.6%, p = 0.041). Women in the intervention group were less likely to use infant formula at 1 and 6 months postpartum (5.6% and 23.5%, p = 0.032; 20.0% and 44.1%, p = 0.032). Related to the process of breastfeeding, partners in the intervention group supported their partners by taking care of the infant, doing housework, and providing emotional support. CONCLUSIONS: Involving the fathers in breastfeeding education could improve the exclusive breastfeeding rate and prolong the duration of exclusive breastfeeding. The mothers appreciated support from the fathers. PMID- 26836961 TI - Experimental warming alters potential function of the fungal community in boreal forest. AB - Fungal community composition often shifts in response to warmer temperatures, which might influence decomposition of recalcitrant carbon (C). We hypothesized that evolutionary trade-offs would enable recalcitrant C-using taxa to respond more positively to warming than would labile C-using taxa. Accordingly, we performed a warming experiment in an Alaskan boreal forest and examined changes in the prevalence of fungal taxa. In a complementary field trial, we characterized the ability of fungal taxa to use labile C (glucose), intermediate C (hemicellulose or cellulose), or recalcitrant C (lignin). We also assigned taxa to functional groups (e.g., free-living filamentous fungi, ectomycorrhizal fungi, and yeasts) based on taxonomic identity. We found that response to warming varied most among taxa at the order level, compared to other taxonomic ranks. Among orders, ability to use lignin was significantly related to increases in prevalence in response to warming. However, the relationship was weak, given that lignin use explained only 9% of the variability in warming responses. Functional groups also differed in warming responses. Specifically, free-living filamentous fungi and ectomycorrhizal fungi responded positively to warming, on average, but yeasts responded negatively. Overall, warming-induced shifts in fungal communities might be accompanied by an increased ability to break down recalcitrant C. This change in potential function may reduce soil C storage under global warming. PMID- 26836962 TI - Exploring the Definition of an Informed Health Care Proxy. PMID- 26836963 TI - Feasibility of Single-Incision Laparoscopic Percutaneous Extraperitoneal Closure for Inguinal Hernia by Inexperienced Pediatric Surgeons: Single-Incision Versus Multi-Incision Randomized Trial for 2 Years. AB - PURPOSE: This study evaluated the stability and risk of single-incision laparoscopic percutaneous extraperitoneal closure (SILPEC) for pediatric inguinal hernia performed by inexperienced pediatric surgeons versus conventional LPEC procedure. METHODS: Between 2011 and 2012, a randomized prospective study was performed comparing SILPEC (n = 37, 16 uni- and 21 bilateral patent processus vaginalis [PPV]) to LPEC (n = 72, 39 uni- and 33 bilateral PPV). The procedures were performed in girls with inguinal hernia by inexperienced pediatric surgeons with the assistance of an expert pediatric surgeon. In SILPEC, a laparoscope was placed through a transumbilical incision. A 2-mm trocar for the grasper was inserted through the same incision and introduced into the extraperitoneal cavity. The tip of the trocar was inserted in the abdominal cavity distant from the umbilical incision by the expert surgeon to avoid any complications caused by the in-line view. Using a special needle, the hernial sac was closed extraperitoneally by the inexperienced surgeon. A statistical survey of the mean age at operation, mean operative time, intra- and postoperative complications, and recurrence in the SILPEC and LPEC groups was performed. RESULTS: There were no significant differences in the mean age or operative time. There were fewer total number of postoperative complications in the SILPEC group compared with the LPEC group (P = .0707). No intraoperative complications or recurrence occurred. CONCLUSIONS: Considering the risks and need to improve endoscopic surgical skills with useful instruments specialized for SILPEC, inexperienced surgeons can successfully perform SILPEC safely under expert pediatric surgeons. PMID- 26836964 TI - Epicochalasines A and B: Two Bioactive Merocytochalasans Bearing Caged Epicoccine Dimer Units from Aspergillus flavipes. AB - Two bioactive merocytochalasans, epicochalasines A (1) and B (2), a new class of cytochalasans bearing unexpected scaffolds consisting of fused aspochalasin and epicoccine dimer moieties, were isolated from the liquid culture broth of Aspergillus flavipes. Both 1 and 2 possess a hendecacyclic 5/6/11/5/6/5/6/5/6/6/5 ring system containing an adamantyl cage and as many as 19 stereogenic centers; however, the fusion patterns of 1 and 2 differ greatly, thus resulting in different carbon skeletons. The absolute configurations of 1 and 2 were determined by X-ray diffraction and calculated ECD, respectively. The biogenetic pathways of 1 and 2 are proposed to involve Diels-Alder and nucleophilic addition reactions. Both 1 and 2 induced significant G2/M-phase cell-cycle arrest. Furthermore, we found that merocytochalasans induce apoptosis in leukemia cells through the activation of caspase-3 and the degradation of PARP. PMID- 26836966 TI - Structural Mechanism for the Fidelity Modulation of DNA Polymerase lambda. AB - The mechanism of DNA polymerase (pol) fidelity is of fundamental importance in chemistry and biology. While high-fidelity pols have been well studied, much less is known about how some pols achieve medium or low fidelity with functional importance. Here we examine how human DNA polymerase lambda (Pol lambda) achieves medium fidelity by determining 12 crystal structures and performing pre-steady state kinetic analyses. We showed that apo-Pol lambda exists in the closed conformation, unprecedentedly with a preformed MgdNTP binding pocket, and binds MgdNTP readily in the active conformation in the absence of DNA. Since prebinding of MgdNTP could lead to very low fidelity as shown previously, it is attenuated in Pol lambda by a hydrophobic core including Leu431, Ile492, and the Tyr505/Phe506 motif. We then predicted and demonstrated that L431A mutation enhances MgdNTP prebinding and lowers the fidelity. We also hypothesized that the MgdNTP-prebinding ability could stabilize a mismatched ternary complex and destabilize a matched ternary complex, and provided evidence with structures in both forms. Our results demonstrate that, while high-fidelity pols follow a common paradigm, Pol lambda has developed specific conformations and mechanisms for its medium fidelity. Structural comparison with other pols also suggests that different pols likely utilize different conformational changes and microscopic mechanisms to achieve their catalytic functions with varying fidelities. PMID- 26836965 TI - Risk of Injurious Fall and Hip Fracture up to 26 y before the Diagnosis of Parkinson Disease: Nested Case-Control Studies in a Nationwide Cohort. AB - BACKGROUND: Low muscle strength has been found in late adolescence in individuals diagnosed with Parkinson disease (PD) 30 y later. This study investigated whether this lower muscle strength also may translate into increased risks of falling and fracture before the diagnosis of PD. METHODS AND FINDINGS: Among all Swedish citizens aged >=50 y in 2005, two nested case-control cohorts were compiled. In cohort I, individuals diagnosed with PD during 1988-2012 (n = 24,412) were matched with up to ten controls (n = 243,363), and the risk of fall-related injuries before diagnosis of PD was evaluated. In cohort II, individuals with an injurious fall in need of emergency care during 1988-2012 (n = 622,333) were matched with one control (n = 622,333), and the risk of PD after the injurious fall was evaluated. In cohort I, 18.0% of cases and 11.5% of controls had at least one injurious fall (p < 0.001) prior to PD diagnosis in the case. Assessed by conditional logistic regression analysis adjusted for comorbid diagnoses and education level, PD was associated with increased risks of injurious fall up to 10 y before diagnosis (odds ratio [OR] 1.19, 95% CI 1.08-1.31; 7 to <10 y before diagnosis) and hip fracture >=15 y before diagnosis (OR 1.36, 95% CI 1.10-1.69; 15-26 y before diagnosis). In cohort II, 0.7% of individuals with an injurious fall and 0.5% of controls were diagnosed with PD during follow-up (p < 0.001). The risk of PD was increased for up to 10 y after an injurious fall (OR 1.18, 95% CI 1.02-1.37; 7 to <10 y after diagnosis). An important limitation is that the diagnoses were obtained from registers and could not be clinically confirmed for the study. CONCLUSIONS: The increased risks of falling and hip fracture prior to the diagnosis of PD may suggest the presence of clinically relevant neurodegenerative impairment many years before the diagnosis of this disease. PMID- 26836967 TI - Indication of direct acoustical cochlea stimulation in comparison to cochlear implants. AB - The new implantable hearing system CodacsTM was designed to close the treatment gap between active middle ear implants and cochlear implants in cases of severe to-profound mixed hearing loss. The CodacsTM actuator is attached to conventional stapes prosthesis during the implantation and thereby provides acoustical stimulation through a stapedotomy to the cochlea. Cochlear implants (CIs) on the other hand are an established treatment option for profoundly deaf patients including mixed hearing losses that are possible candidates for the CodacsTM. In this retrospective study, we compared the clinical outcome of 25 patients with the CodacsTM (>=3 month post-activation) to 54 CI patients (two years post activation) with comparable pre-operative bone conduction (BC) thresholds that were potential candidates for both categories of devices. The word recognition score (Freiburg monosyllables test) in quiet was significantly (p < 0.05) better in the CodacsTM than in the corresponding CI patients for average pre-operative bone conduction below 60 dB HL and equal in patients with a pre-operative BC PTA between 60 and 70 dB HL. Speech in noise intelligibility (HSM sentences test at +10 dB SNR) was significantly (p < 0.001) better in CodacsTM (80% median) than in CI patients (25% median) in all tested groups. Our results indicate for patients with sufficient cochlear reserve that speech intelligibility in noise with the CodacsTM hearing implant is significantly better than with a CI. Further, results in CodacsTM were better predictable, encouraging the extension of the indication to patients with less cochlear reserve than reported here. PMID- 26836968 TI - Channeling your inner ear potassium: K(+) channels in vestibular hair cells. AB - During development of vestibular hair cells, K(+) conductances are acquired in a specific pattern. Functionally mature vestibular hair cells express different complements of K(+) channels which uniquely shape the hair cell receptor potential and filtering properties. In amniote species, type I hair cells (HCI) have a large input conductance due to a ubiquitous low-voltage-activated K(+) current that activates with slow sigmoidal kinetics at voltages negative to the membrane resting potential. In contrast type II hair cells (HCII) from mammalian and non-mammalian species have voltage-dependent outward K(+) currents that activate rapidly at or above the resting membrane potential and show significant inactivation. A-type, delayed rectifier and calcium-activated K(+) channels contribute to the outward K(+) conductance and are present in varying proportions in HCII. In many species, K(+) currents in HCII in peripheral locations of vestibular epithelia inactivate more than HCII in more central locations. Two types of inward rectifier currents have been described in both HCI and HCII. A rapidly activating K(+)-selective inward rectifier current (IK1, mediated by Kir2.1 channels) predominates in HCII in peripheral zones, whereas a slower mixed cation inward rectifier current (Ih), shows greater expression in HCII in central zones of vestibular epithelia. The implications for sensory coding of vestibular signals by different types of hair cells are discussed. This article is part of a Special Issue entitled . PMID- 26836969 TI - The effects of baseball bat mass properties on swing mechanics, ground reaction forces, and swing timing. AB - Swing trajectory and ground reaction forces (GRF) of 30 collegiate baseball batters hitting a pitched ball were compared between a standard bat, a bat with extra weight about its barrel, and a bat with extra weight in its handle. It was hypothesised that when compared to a standard bat, only a handle-weighted bat would produce equivalent bat kinematics. It was also hypothesised that hitters would not produce equivalent GRFs for each weighted bat, but would maintain equivalent timing when compared to a standard bat. Data were collected utilising a 500 Hz motion capture system and 1,000 Hz force plate system. Data between bats were considered equivalent when the 95% confidence interval of the difference was contained entirely within +/-5% of the standard bat mean value. The handle weighted bat had equivalent kinematics, whereas the barrel-weighted bat did not. Both weighted bats had equivalent peak GRF variables. Neither weighted bat maintained equivalence in the timing of bat kinematics and some peak GRFs. The ability to maintain swing kinematics with a handle-weighted bat may have implications for swing training and warm-up. However, altered timings of kinematics and kinetics require further research to understand the implications on returning to a conventionally weighted bat. PMID- 26836970 TI - Catalytic Hydrotreatment of Humins in Mixtures of Formic Acid/2-Propanol with Supported Ruthenium Catalysts. AB - The catalytic hydrotreatment of humins, which are the solid byproducts from the conversion of C6 sugars (glucose, fructose) into 5-hydroxymethylfurfural (HMF) and levulinic acid (LA), by using supported ruthenium catalysts has been investigated. Reactions were carried out in a batch setup at elevated temperatures (400 degrees C) by using a hydrogen donor (formic acid (FA) in isopropanol (IPA) or hydrogen gas), with humins obtained from d-glucose. Humin conversions of up to 69 % were achieved with Ru/C and FA, whereas the performance for Ru on alumina was slightly poorer (59 % humin conversion). Humin oils were characterized by using a range of analytical techniques (GC, GC-MS, GCxGC, gel permeation chromatography) and were shown to consist of monomers, mainly alkyl phenolics (>45 % based on compounds detectable by GC) and higher oligomers. A reaction network for the reaction is proposed based on structural proposals for humins and the main reaction products. PMID- 26836971 TI - Nanoengineering of a Supramolecular Gel by Copolymer Incorporation: Enhancement of Gelation Rate, Mechanical Property, Fluorescence, and Conductivity. AB - In the quest to engineer the nanofibrillar morphology of folic acid (F) gel, poly(4-vinylpyridine-co-styrene) (PVPS) is judiciously integrated as a polymeric additive because of its potential to form H-bonding and pi-stacking with F. The hybrid gels are designated as F-PVPSx gels, where x denotes the amount of PVPS (mg) added in 2 mL of F gel (0.3%, w/v). The assistance of PVPS in the gelation of F is manifested from the drop in critical gelation concentration and increased fiber diameter and branching of F-PVPSx gels compared to that of F gel. PVPS induces a magnificent improvement of mechanical properties: a 500 times increase of storage modulus and ~62 times increase of yield stress in the F-PVPS5 gel compared to the F gel. The complex modulus also increases with increasing PVPS concentration with a maximum in F-PVPS5 gel. Creep recovery experiments suggest PVPS induced elasticity in the otherwise viscous F gel. The fluorescence intensity of F-PVPSx gels at first increases with increasing PVPS concentration showing maxima at F-PVPS5 gel and then slowly decreases. Gelation is monitored by time-dependent fluorescence spectroscopy, and it is observed that F and F-PVPSx gels exhibit perfectly opposite trend; the former shows a sigmoidal decrease in fluorescence intensity during gelation, but the latter shows a sigmoidal increase. The gelation rate constants calculated from Avrami treatment on the time-dependent fluorescence data manifest that PVPS effectively enhances the gelation rate showing a maximum for F-PVPS5 gel. The hybrid gel exhibit 5 orders increase of dc conductivity than that of F-gel showing semiconducting nature in the current-voltage plot. The Nyquist plot in impedance spectra of F-PVPS5 xerogel exhibit a depressed semicircle with a spike at lower frequency region, and the equivalent circuit represents a complex combination of resistance capacitance circuits attributed to the hybrid morphology of the gel fibers. PMID- 26836973 TI - Chitosan- and polypropylene-oriented surface modification using excimer laser and their biocompatibility study. AB - Surface modification of medical polymers is carried out to improve biocompatibility. In this study, conventional polymers (chitosan and polypropylene) were modified to laser at different features (oriented and non oriented) to create a vast range of physicochemical characteristics on the surface of polymers and investigate their effects on biocompatibility of treated surfaces. Atomic force microscope (AFM) was applied to study the morphology of treated samples in comparison with those of the untreated PS. Contact angle analyses were used to evaluate the wettability and surface energy of the treated films. AFM studies showed that after laser treatment, some distinctive nanostructures are created on the surface of polymers. The data from contact angle measurements demonstrated that laser irradiation created surfaces with a vast range of properties in the wettability point of view. The cellular results revealed that after surface modification by laser irradiation, biocompatibility of polymeric films, especially oriented films was enhanced. PMID- 26836972 TI - IL15 polymorphism is associated with advanced fibrosis, inflammation-related biomarkers and virological response in human immunodeficiency virus/hepatitis C virus coinfection. AB - BACKGROUND & AIMS: IL15 is an essential cytokine in both innate and adaptive immune response against hepatitis C virus (HCV) infection. The aim was to analyze whether IL15 rs10833 is associated with liver disease severity and response to pegylated-interferon-alpha plus ribavirin (pegIFN-alpha/RBV) therapy in human immunodeficiency virus (HIV)-/HCV-co-infected patients. METHODS: A retrospective study was performed in 315 patients who started pegIFN-alpha/RBV therapy. Liver fibrosis stage was characterized in 286 patients. IL15 rs10833 and IL28B rs12980275 were genotyped by GoldenGate. The primary outcomes were: (a) advanced liver fibrosis evaluated by liver biopsy (F3-F4) or transient elastography (liver stiffness values >=9.5 Kpa); (b) sustained virological response (SVR). The secondary outcome variable was the levels of serum biomarkers of inflammation. RESULTS: Patients with rs10833 AA genotype had increased odds of having advanced fibrosis (adjusted odds ratio (aOR) = 2.30; P = 0.019), particularly in males (aOR = 2.24; P = 0.040), patients with HCV serum viral load (HCV-RNA) <500 000 IU/ml (aOR = 5.14; P = 0.018) and patients with IL28B rs12980275 AG/GG genotypes (aOR = 2.51; P = 0.046). Moreover, rs10833 AA genotype was significantly associated with higher levels of hepatocyte growth factor (adjusted arithmetic mean ratio (aAMR) = 1.50; P = 0.016), sICAM-1 (aAMR = 1.57; P = 0.025) and sVCAM 1 (aAMR = 1.56; P = 0.007). Finally, patients with rs10833 AA genotype had increased odds of achieving SVR (aOR = 3.12; P = 0.006), particularly in males (aOR = 3.69; P = 0.005), GT1/4 patients (aOR = 3.59; P = 0.006), patients with advanced fibrosis (aOR = 4.64; P = 0.021), HCV-RNA >=500 000 IU/ml (aOR = 3.92; P = 0.007) and patients with IL28B rs12980275 AG/GG genotype (aOR = 2.98; P = 0.041). CONCLUSIONS: The presence of IL15 rs10833 AA genotype in HIV-/HCV-co infected patients was associated with advanced liver fibrosis, inflammation related biomarkers and increased rates of SVR to pegIFN-alpha/RBV therapy. PMID- 26836974 TI - Reply to "Comment on 'Reaction Coordinates and Pathways of Mechanochemical Transformations'". PMID- 26836976 TI - dbAARD & AGP: A computational pipeline for the prediction of genes associated with age related disorders. AB - The atrocious behavioral and physiological shift with aging accelerate occurrence of deleterious disorders. Contemporary research is focused at uncovering the role of genetic associations in age-related disorders (ARDs). While the completion of the Human Genome Project and the HapMap project has generated huge amount of data on genetic variations; Genome-Wide Association Studies (GWAS) have identified genetic variations, essentially SNPs associated with several disorders including ARDs. However, a repository that houses all such ARD associations is lacking. The present work is aimed at filling this void. A database, dbAARD (database of Aging and Age Related Disorders) has been developed which hosts information on more than 3000 genetic variations significantly (p-value <0.05) associated with 51 ARDs. Furthermore, a machine learning based gene prediction tool AGP (Age Related Disorders Gene Prediction) has been constructed by employing rotation forest algorithm, to prioritize genes associated with ARDs. The tool achieved an overall accuracy in terms of precision 75%, recall 76%, F-measure 76% and AUC 0.85. Both the web resources have been made available online at http://genomeinformatics.dce.edu/dbAARD/ and http://genomeinformatics.dce.edu/AGP/ respectively for easy retrieval and usage by the scientific community. We believe that this work may facilitate the analysis of plethora of variants associated with ARDs and provide cues for deciphering the biology of aging. PMID- 26836975 TI - Toward rapid learning in cancer treatment selection: An analytical engine for practice-based clinical data. AB - OBJECTIVE: Wide-scale adoption of electronic medical records (EMRs) has created an unprecedented opportunity for the implementation of Rapid Learning Systems (RLSs) that leverage primary clinical data for real-time decision support. In cancer, where large variations among patient features leave gaps in traditional forms of medical evidence, the potential impact of a RLS is particularly promising. We developed the Melanoma Rapid Learning Utility (MRLU), a component of the RLS, providing an analytical engine and user interface that enables physicians to gain clinical insights by rapidly identifying and analyzing cohorts of patients similar to their own. MATERIALS AND METHODS: A new approach for clinical decision support in Melanoma was developed and implemented, in which patient-centered cohorts are generated from practice-based evidence and used to power on-the-fly stratified survival analyses. A database to underlie the system was generated from clinical, pharmaceutical, and molecular data from 237 patients with metastatic melanoma from two academic medical centers. The system was assessed in two ways: (1) ability to rediscover known knowledge and (2) potential clinical utility and usability through a user study of 13 practicing oncologists. RESULTS: The MRLU enables physician-driven cohort selection and stratified survival analysis. The system successfully identified several known clinical trends in melanoma, including frequency of BRAF mutations, survival rate of patients with BRAF mutant tumors in response to BRAF inhibitor therapy, and sex based trends in prevalence and survival. Surveyed physician users expressed great interest in using such on-the-fly evidence systems in practice (mean response from relevant survey questions 4.54/5.0), and generally found the MRLU in particular to be both useful (mean score 4.2/5.0) and useable (4.42/5.0). DISCUSSION: The MRLU is an RLS analytical engine and user interface for Melanoma treatment planning that presents design principles useful in building RLSs. Further research is necessary to evaluate when and how to best use this functionality within the EMR clinical workflow for guiding clinical decision making. CONCLUSION: The MRLU is an important component in building a RLS for data driven precision medicine in Melanoma treatment that could be generalized to other clinical disorders. PMID- 26836977 TI - Specific inflammatory response of Anemonia sulcata (Cnidaria) after bacterial injection causes tissue reaction and enzymatic activity alteration. AB - The evolution of multicellular organisms was marked by adaptations to protect against pathogens. The mechanisms for discriminating the ''self'' from ''non self" have evolved into a long history of cellular and molecular strategies, from damage repair to the co-evolution of host-pathogen interactions. We investigated the inflammatory response in Anemonia sulcata (Cnidaria: Anthozoa) following injection of substances that varied in type and dimension, and observed clear, strong and specific reactions, especially after injection of Escherichia coli and Vibrio alginolyticus. Moreover, we analyzed enzymatic activity of protease, phosphatase and esterase, showing how the injection of different bacterial strains alters the expression of these enzymes and suggesting a correlation between the appearance of the inflammatory reaction and the modification of enzymatic activities. Our study shows for the first time, a specific reaction and enzymatic responses following injection of bacteria in a cnidarian. PMID- 26836978 TI - Red and white Chinook salmon: genetic divergence and mate choice. AB - Chinook salmon (Oncorhynchus tshawytscha) exhibit extreme differences in coloration of skin, eggs and flesh due to genetic polymorphisms affecting carotenoid deposition, where colour can range from white to bright red. A sympatric population of red and white Chinook salmon occurs in the Quesnel River, British Columbia, where frequencies of each phenotype are relatively equal. In our study, we examined evolutionary mechanisms responsible for the maintenance of the morphs, where we first tested whether morphs were reproductively isolated using microsatellite genotyping, and second, using breeding trials in seminatural spawning channels, we tested whether colour assortative mate choice could be operating to maintain the polymorphism in nature. Next, given extreme difference in carotenoid assimilation and the importance of carotenoids to immune function, we examined mate choice and selection between colour morphs at immune genes (major histocompatibility complex genes: MHC I-A1 and MHC II-B1). In our study, red and white individuals were found to interbreed, and under seminatural conditions, some degree of colour assortative mate choice (71% of matings) was observed. We found significant genetic differences at both MHC genes between morphs, but no evidence of MHC II-B1-based mate choice. White individuals were more heterozygous at MHC II-B1 compared with red individuals, and morphs showed significant allele frequency differences at MHC I-A1. Although colour assortative mate choice is likely not a primary mechanism maintaining the polymorphisms in the population, our results suggest that selection is operating differentially at immune genes in red and white Chinook salmon, possibly due to differences in carotenoid utilization. PMID- 26836980 TI - Dermoscopy as a supportive instrument in the differentiation of the main types of acquired keratoderma due to dermatological disorders. PMID- 26836979 TI - Decreased expression of activin A receptor 1C may result in Ca(2+) -induced aberrant skin hypersensitivity. PMID- 26836981 TI - Comparison of implant supported mandibular overdentures and conventional dentures on quality of life: a systematic review and meta-analysis of randomized controlled studies. AB - BACKGROUND: Conventional complete dentures and implant supported overdentures are commonly used by dentists to treat completely edentulous mandibular arches. There have been problems associated with retention and stability while treating completely edentulous mandibular arches compared to maxillary arches. Many factors have been attributed to this, primarily focusing on the decreased area available for support and increased resorption. Implant supported overdentures have increased the treatment options for resorbed ridges, especially the mandible. However, no reports have proved the superiority of one treatment option over the other, especially in terms of patient-centric outcome measures such as the Oral Health Impact Profile (OHIP). Hence, this meta-analysis was conducted. METHODS: A literature search of Medline (via PubMed), the Cochrane Central Register of Clinical Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) was performed. The reviewers screened titles, abstracts and performed full-text screening of eligible studies. The references from these studies were further screened for additional relevant studies. A random effects model was applied to measure the significance of the per cent mean difference in OHIP scale improvement between implant and conventional dentures. The Cochrane Risk of Bias Tool was applied to assess the selection, ascertainment and selective reporting biases. RESULTS: Five studies were reviewed and identified. Results of 441 patients (228 implant and 213 conventional) were pooled for analysis of primary outcome and other secondary outcomes. A forest plot of total OHIP scores and for secondary outcomes were obtained between the interventions. Results of 441 patients (228 implant and 213 conventional) were pooled for analysis of primary outcome with a mean difference [95% confidence interval] in the score of -30.72[-48.39, -13.05]; mean difference [95% confidence interval] in the score of -26.45[-43.56, -9.35] for functional limitation; -29.16[-60.89, 2.56] for physical pain; -77.61[-154.63, -0.60] for psychological discomfort; 33.70[-47.96, -19.44] for physical disability; -41.17[-55.93, -26.40] for psychological disability; -17.27[-29.44, 5.10] for social disability; and -28.45[ 33.97, -22.92] for handicap. A statistically significant difference favouring the implant group was obtained except for physical pain. CONCLUSIONS: The implant overdenture group performed better in regard to patient satisfaction as measured using the OHIP questionnaire. Further studies are required to identify superiority between the two treatment options. PMID- 26836983 TI - K2 Mn4 O8 /Reduced Graphene Oxide Nanocomposites for Excellent Lithium Storage and Adsorption of Lead Ions. AB - Ion diffusion efficiency at the solid-liquid interface is an important factor for energy storage and adsorption from aqueous solution. Although K2 Mn4 O8 (KMO) exhibits efficient ion diffusion and ion-exchange capacities, due to its high interlayer space of 0.70 nm, how to enhance its mass transfer performance is still an issue. Herein, novel layered KMO/reduced graphene oxide (RGO) nanocomposites are fabricated through the anchoring of KMO nanoplates on RGO with a mild solution process. The face-to-face structure facilitates fast transfer of lithium and lead ions; thus leading to excellent lithium storage and lead ion adsorption. The anchoring of KMO on RGO not only increases electrical conductivity of the layered nanocomposites, but also effectively prevents aggregation of KMO nanoplates. The KMO/RGO nanocomposite with an optimal RGO content exhibits a first cycle charge capacity of 739 mA h g-1 , which is much higher than that of KMO (326 mA h g-1 ). After 100 charge-discharge cycles, it still retains a charge capacity of 664 mA h g-1 . For the adsorption of lead ions, the KMO/RGO nanocomposite exhibits a capacity of 341 mg g-1 , which is higher than those of KMO (305 mg g-1 ) and RGO (63 mg g-1 ) alone. PMID- 26836982 TI - Self-synthesizing transposons: unexpected key players in the evolution of viruses and defense systems. AB - Self-synthesizing transposons are the largest known transposable elements that encode their own DNA polymerases (DNAP). The Polinton/Maverick family of self synthesizing transposons is widespread in eukaryotes and abundant in the genomes of some protists. In addition to the DNAP and a retrovirus-like integrase, most of the polintons encode homologs of the major and minor jelly-roll capsid proteins, DNA-packaging ATPase and capsid maturation protease. Therefore, polintons are predicted to alternate between the transposon and viral lifestyles although virion formation remains to be demonstrated. Polintons are related to a group of eukaryotic viruses known as virophages that parasitize on giant viruses of the family Mimiviridae and another recently identified putative family of polinton-like viruses (PLV) predicted to lead a similar, dual life style. Comparative genomic analysis of polintons, virophages, PLV and the other viruses with double-stranded (ds)DNA genomes infecting eukaryotes and prokaryotes suggests that the polintons evolved from bacterial tectiviruses and could have been the ancestors of a broad range of eukaryotic viruses including adenoviruses and members of the proposed order 'Megavirales' as well as linear cytoplasmic plasmids. Recently, a group of predicted self-synthesizing transposons was discovered also in prokaryotes. These elements, denoted casposons, encode a DNAP and a homolog of the CRISPR-associated Cas1 endonuclease that has an integrase activity but no capsid proteins. Thus, unlike polintons, casposons appear to be limited to the transposon life style although they could have evolved from viruses. The casposons are thought to have played a pivotal role in the origin of the prokaryotic adaptive immunity, giving rise to the adaptation module of the CRISPR-Cas systems. PMID- 26836984 TI - Synthesis and Dynamics of Nanosized Phenylene-Ethynylene-Butadiynylene Rotaxanes and the Role of Shape Persistence. AB - Phenylacetylene-based [2]rotaxanes were synthesized by a covalent-template approach by aminolysis of the corresponding prerotaxanes. The wheel and the bulky stoppers are made of phenylene-ethynylene-butadiynylene macrocycles of the same size. The stoppers are large enough to enable the synthesis and purification of the rotaxane. However, the wheel unthreads from the axle at elevated temperatures. The deslipping kinetics and the activation parameters were determined. We described theoretically the unthreading by state-of-the-art DFT based molecular-mechanics models and a string method for the simulation of rare events. This approach enabled us to characterize in detail the unthreading mechanism, which involves the folding of the stopper during its passage through the wheel opening, a process that defies intuitive geometrical considerations. The conformational and energetic features of the transition allowed us to infer the molecular residues controlling the disassembly timescale. PMID- 26836986 TI - Convergent and divergent validity of K-SADS-PL anxiety and attention deficit hyperactivity disorder diagnoses in a clinical sample of school-aged children. AB - Background The Schedule for Affective Disorders and Schizophrenia for School Age Children, Present and Lifetime Version (K-SADS-PL) is a commonly used diagnostic interview both in research and clinical settings, yet published data on the psychometric properties of the interview generated diagnoses are scarce. Aims To examine the convergent and divergent validity of the Norwegian version of the K SADS-PL current diagnoses of anxiety disorders and attention deficit hyperactivity disorder (ADHD). Method Participants were 105 children aged 7-13 years referred for treatment at child mental health clinics and 36 controls. Diagnostic status was determined based on K-SADS-PL interviews with the mothers. Child and mother reported child symptoms of anxiety on the Multidimensional Anxiety Scale for Children and teachers reported anxiety symptoms on the Teacher Report Form. Mother and teacher reported on symptoms of ADHD on the Disruptive Behavior Rating Scale. Results Rating scale data from multiple informants in a clinical sample and healthy controls supported the convergent and divergent validity of K-SADS-PL anxiety diagnoses combined, and, specifically, the diagnoses of separation anxiety disorder, social phobia, and specific phobia. Support was also observed for convergent and divergent validity of ADHD diagnoses, including the predominately inattentive subtype. Conclusion The K-SADS PL generates valid diagnoses of anxiety disorders and ADHD. PMID- 26836985 TI - Trastuzumab and target-therapy side effects: Is still valid to differentiate anthracycline Type I from Type II cardiomyopathies? AB - The improvement in cancer therapy and the increasing number of long term survivors unearth the issue of cardiovascular side effects of anticancer treatments. As a paradox in cancer survivors, delayed cardiotoxicity has emerged as a significant problem. Two categories of cardiotoxic side effects of antineoplastic drugs have been previously proposed: Type I cardiotoxicity, defined as permanent cardiotoxicity, is usually caused by anthracyclines; Type II cardiotoxicity, considered as reversible cardiotoxicity, has been mainly related to monoclonal antibodies. The cardiotoxicity of antibodies has been associated to trastuzumab, a humanized anti-ErbB2 monoclonal antibody currently in clinical use for the therapy of breast carcinomas, which induces cardiac dysfunction when used in monotherapy, or in combination with anthracyclines. Furthermore, recent retrospective studies have shown an increased incidence of heart failure and/or cardiomyopathy in patients treated with trastuzumab, that can persist many years after the conclusion of the therapy, thus suggesting that the side toxic effects are not always reversible as it was initially proposed. On the other hand, early detection and prompt therapy of anthracycline associated cardiotoxicity can lead to substantial recovery of cardiac function. On the basis of these observations, we propose to find a new different classification for cardiotoxic side effects of drugs used in cancer therapy. PMID- 26836987 TI - Management of postoperative atrial fibrillation after cardiac surgery. AB - PURPOSE OF REVIEW: Postoperative atrial fibrillation (POAF) occurs commonly after cardiac surgery and is associated with a number of adverse outcomes. This article will review the available evidence on the prevention and treatment of atrial fibrillation after cardiac surgery. Using this knowledge, we propose a conceptual framework on the management of patients with POAF during various phases after cardiac surgery. RECENT FINDINGS: Perioperative beta-blockade is the cornerstone in preventing POAF after cardiac surgery. Results from randomized trials do not support routine use of colchicine or corticosteroids to prevent POAF. There is no study examining the impact of rate versus rhythm control on 'hard' clinical outcomes such as mortality or stroke in the cardiac surgical population. Furthermore, there is a paucity of research on the optimal timing and choice of oral anticoagulation among POAF cardiac surgical patients who are at risk for stroke. SUMMARY: In spite of the plethora of therapies available to treat and prevent POAF in the cardiac surgical population, there is little data to address whether they can improve key clinical outcomes such as death or stroke. Guideline recommendations on rate/rhythm control and oral anticoagulation for stroke prevention in the cardiac surgical population are largely extrapolated from studies of nonsurgical atrial fibrillation patients. Further research is needed to address these key atrial fibrillation management issues specific to the cardiac surgical population. PMID- 26836989 TI - From the Editor. PMID- 26836990 TI - Designing Technology to Address Parent Uncertainty in Childhood Cancer. AB - The stress and uncertainty created by a child's cancer diagnosis and treatment can affect parent and child functioning. Health technology provides a potential avenue for intervention delivery. Interviews were conducted with parents of children diagnosed with cancer to discover their needs following diagnosis and design a relevant mobile application. Treatment experience was the overarching theme. Subthemes included the emotional response, use of information, and environmental factors. Technology was used primarily to seek out information and communicate with others. Health technologies are gaining popularity and have the potential to be beneficial for patients and families throughout the treatment experience. PMID- 26836991 TI - Empowered Consumers and the Health Care Team: A Dynamic Model of Health Informatics. AB - This article presents a dynamic new model of health informatics. Within the model, the focus of health informatics changes from the provider to the consumer and incorporates the dynamic relationship of technological change to health care. Bioinformatics is the scientific discipline that is translated into care through the practice of health informatics. The loci of health informatics practices are the consumer (consumer informatics), the patient (clinical informatics), and the community (public health informatics). The continuum from individual to community interacts with and contributes to health care technology, which is represented as a constantly changing progressive wave. PMID- 26836992 TI - Mindful Communication for Caring Online. AB - Six studies containing information related to conveying and sustaining caring in online nursing classrooms were analyzed for communication patterns among faculty and students. Six consistent communicative elements emerged from this analysis: offering full presence, acknowledging shared humanity, attending to the individual, asking for and providing frequent clarification, demonstrating flexibility, and pointing out favorable opportunities while acknowledging challenges. These elements reflected key aspects of Jean Watson's Caring Science and Thich Nhat Hanh's Mindfulness trainings, prompting guidelines and suggestions for engaging in mindful caring communication online. PMID- 26836993 TI - On Virtual Presence. AB - Advances in health care and communication technology have expanded nursing practice to nontraditional environments that preclude the physical presence of the nurse for a caring encounter. An increasing number of nurses are creating and maintaining nurse-patient relationships and practicing in a diverse range of specialties in virtual/distance environments. Can nursing presence as a caring modality be "real" in a virtual/distance environment? A new ontology of nursing presence is offered that transcends people, place, space, and time. PMID- 26836994 TI - Cyberbullying in Adolescence: A Concept Analysis. AB - The aim of this article was to present a detailed analysis of the concept of cyberbullying. Research on the topic of cyberbullying is growing exponentially, but not all studies use the same definition to examine this concept. A concept analysis in the style of Walker and Avant was used to analyze cyberbullying. Literature was retrieved from the databases of CINAHL and PubMed between the years 2009 and October 2014 using the key word "cyberbullying." Twenty-five English-language articles were located that delineated a definition of cyberbullying. First, articles were analyzed to discover the defining attributes of cyberbullying. Second, antecedents, consequences, and related terms of cyberbullying were examined. Third, an operational definition of cyberbullying is proposed on the basis of a consensus of the review. This review proposes that the defining attributes of cyberbullying are: (1) electronic form of contact (2) an aggressive act (3) intent (4) repetition (publicity), and (5) harm of the victim. The antecedents most often mentioned were lower self-esteem, higher levels of depression, and social isolation and the consequences were academic problems and affective disorders. A single concise definition of cyberbullying was created that can be utilized by health care providers to educate their patients and families about cyberbullying. This definition also can be used to guide research to develop effective interventions. PMID- 26836995 TI - Gossamer Threads: Commentary on the Impact of Digital Technology on the Developing Brain and the Capacity for Empathy. AB - This essay explores the impact of digital technology on brain development and other areas of human growth including the capacity for empathy, which is fundamental to successful relationships, is an essential survival skill, and is an important source of moral knowledge. Reflections on a teenaged daughter's immersion in technology, coupled with evidence for the mixed consequences of such, weave together the gossamer threads of disparate, sometimes conflicting information about the explosion of digital technology over the past few decades, the impossibility of multitasking, the mixed effects of digital technology on brain development, and what it all might mean for human development generally and the moral capacity for empathic response in particular. While the essence of the commentary is intentionally interdisciplinary and weaves together disparate threads of multidisciplinary knowledge, it has important implications for nursing with its relational core, unique as well as shared bodies of moral and scientific knowledge, and interprofessional health care goals to maximize human growth and well-being across the life span in both health and illness. PMID- 26836996 TI - Partnership With Parents of Technology-Dependent Children: Clarification of the Concept. AB - A strategy based on the Hybrid Model of Concept Development was used to integrate previous concept analyses and research with data from interviews with parents and nurses caring for children dependent on technology to clarify the concept. Partnership was generally described positively in the literature, but some cautions were noted. Six characteristics of partnering were identified from the fieldwork data: respect, flexibility, caring professionalism, communication, acknowledgment of parental control, and support for parents. The concept of participation is clarified and extended to a unique area of nursing practice, the care of children dependent on technology in the home. PMID- 26836997 TI - The Evolution of Data-Information-Knowledge-Wisdom in Nursing Informatics. AB - The data-information-knowledge-wisdom (DIKW) model has been widely adopted in nursing informatics. In this article, we examine the evolution of DIKW in nursing informatics while incorporating critiques from other disciplines. This includes examination of assumptions of linearity and hierarchy and an exploration of the implicit philosophical grounding of the model. Two guiding questions are considered: (1) Does DIKW serve clinical information systems, nurses, or both? and (2) What level of theory does DIKW occupy? The DIKW model has been valuable in advancing the independent field of nursing informatics. We offer that if the model is to continue to move forward, its role and functions must be explicitly addressed. PMID- 26836998 TI - Transnationalism: A Framework for Advancing Nursing Research With Contemporary Immigrants. AB - This article advances nursing research by presenting transnationalism as a framework for inquiry with contemporary immigrants. Transnationalism occurs when immigrants maintain relationships that transcend the geographical borders of their origin and host countries. Immigrants use those relationships to experience health differently within concurrent socioeconomic, political, and cultural contexts than national situated populations. Nurse researchers are called upon to consider these trans-border relationships when exploring the health of contemporary immigrants. Such consideration is needed to develop relevant research designs, methods, analysis, and dissemination strategies. PMID- 26836999 TI - Coding, Constant Comparisons, and Core Categories: A Worked Example for Novice Constructivist Grounded Theorists. AB - Grounded theory method has been described extensively in the literature. Yet, the varying processes portrayed can be confusing for novice grounded theorists. This article provides a worked example of the data analysis phase of a constructivist grounded theory study that examined family presence during resuscitation in acute health care settings. Core grounded theory methods are exemplified, including initial and focused coding, constant comparative analysis, memo writing, theoretical sampling, and theoretical saturation. The article traces the construction of the core category "Conditional Permission" from initial and focused codes, subcategories, and properties, through to its position in the final substantive grounded theory. PMID- 26837001 TI - Computed Tomography Estimation of Cochlear Duct Length Can Predict Full Insertion in Cochlear Implantation. AB - OBJECTIVE: To compare the rates of full insertion of electrodes and hearing outcomes obtained with 28-mm and 31-mm cochlear implant electrode arrays. To assess whether cochlear duct length (CDL) estimated by preoperative computed tomography (CT) predicts whether an electrode is fully inserted. STUDY DESIGN: A cohort study compared electrodes inserted and hearing outcomes after implantation with 28-mm or 31-mm arrays. CDL estimated from preoperative CT was compared in patients in whom full insertion of the 28-mm array was achieved compared with patients in whom at least one basal electrode was outside the cochlea. SETTING: Tertiary referral cochlear implantation center. PATIENTS: One hundred forty-eight patients implanted with 28-mm cochlear implant arrays (175 devices) and 74 patients implanted with 31-mm arrays (88 devices). INTERVENTION: Cochlear implantation with 28-mm or 31-mm array. MAIN OUTCOME MEASURES: Active electrodes at first programming, and at subsequent follow-ups. Bamford-Kowal-Bench sentence and auditory speech sound evaluation test results at 2 to 3 months in adult patients. CDL predicted by preoperative CT. RESULTS: There was no difference in full insertion between the 28-mm and 31-mm array cohorts (p = 0.22). Early hearing outcomes at 2 to 3 months showed no difference in mean auditory speech sound evaluation (p = 0.19) or Bamford-Kowal-Bench results (p = 0.853) between the 28-mm and 31-mm cohorts. CDL was shorter in the 22 patients with less than full insertion of the array with a mean length of 28.7 mm compared with 29.6 mm in the 42 patients in whom full insertion was achieved (p = 0.046). CONCLUSION: CT estimation of CDL predicts full insertion after cochlear implantation. Insertion depth does not affect early hearing outcome. PMID- 26837000 TI - Focused grid-based resampling for protein docking and mapping. AB - The fast Fourier transform (FFT) sampling algorithm has been used with success in application to protein-protein docking and for protein mapping, the latter docking a variety of small organic molecules for the identification of binding hot spots on the target protein. Here we explore the local rather than global usage of the FFT sampling approach in docking applications. If the global FFT based search yields a near-native cluster of docked structures for a protein complex, then focused resampling of the cluster generally leads to a substantial increase in the number of conformations close to the native structure. In protein mapping, focused resampling of the selected hot spot regions generally reveals further hot spots that, while not as strong as the primary hot spots, also contribute to ligand binding. The detection of additional ligand binding regions is shown by the improved overlap between hot spots and bound ligands. PMID- 26837002 TI - Dickkopf-related Protein 3 as a Sensitive and Specific Marker for Cerebrospinal Fluid Leaks. AB - HYPOTHESIS: Cerebrospinal fluid (CSF) can be identified by using an enzyme-linked immunosorbent assay (ELISA) for Dickkopf-related protein 3 (DKK3). BACKGROUND: Cerebrospinal fluid leakage from the subarachnoid space is a potentially alarming condition that, left unrepaired, may result in increased risk of meningitis and encephalitis. Current biochemical methods of CSF leak detection involve using beta-2-transferrin-based or beta trace protein-based assays, both of which, at present, have limitations that hinder practical clinical application. This study presents the immunological detection of the CSF-enriched protein DKK3 as a method for detection of a CSF leak. METHODS: Antibodies against DKK3 were generated in rabbits and goats immunized with recombinant human DKK3. Varying dilutions and combinations of human CSF and serum were tested on immunoblots and sandwich ELISA using antibodies to DKK3. RESULTS: ELISA data show that there is a negligible amount of detectable DKK3 in serum samples compared with CSF samples. Inclusion of sera (up to 30%) in a sample containing CSF failed to produce a positive signal, whereas concentrations of CSF as low as 1% produced a positive signal. The minimum concentration required for reliable CSF detection in a sandwich ELISA was determined to be 0.5 MUl. CONCLUSION: ELISA sandwich assays for DKK3 can reliably detect the presence of as little as 0.5 MUl of human CSF, even in the presence of excessive serum. This study provides quantitative evidence of the utility of DKK3 immunoreactivity as an assay for the presence of CSF in samples that contain contaminating sera. The robustness of this assay has allowed for the development of a rapid, point of care test for the detection of CSF in clinical and surgical setting. PMID- 26837004 TI - Seroprevalence of Antibodies to Pertussis Toxin among Different Age Groups in Thailand after 37 Years of Universal Whole-Cell Pertussis Vaccination. AB - Despite the high coverage of prophylactic vaccine against Bordetella pertussis infection in many countries for more than three decades, pertussis remains a common vaccine-preventable disease. Infections have been detected more commonly in countries using acellular pertussis vaccine in their Expanded Program of Immunization. Thailand implemented a routine infant immunization program with whole-cell pertussis vaccine in 1977, and since 1992, the national vaccine policy has offered a five-dose whole-cell pertussis vaccine for children given at the ages of 2, 4, 6, 18, and 48 months. This study aimed to investigate the seroprevalence of antibodies to pertussis toxin among healthy people across all ages to determine the level of whole-cell vaccine-induced immunity in the population, and to identify which age group should be targeted for a booster dose. The lowest seronegative rate and highest geometric mean concentrations were found in the 0-10 years age group, corresponding to their recent pertussis vaccination. The proportion of people with undetectable IgG level was prominent, starting after 11 years of age onwards. Now that a reduced-dose pertussis vaccine with fewer adverse effects is available, a booster dose during adolescence should be considered in order to reduce the incidence of pertussis disease. Further studies exploring how long the reduced-dose pertussis vaccine can provide protective immunity against pertussis disease when administered to adults and adolescents should also be performed. PMID- 26837003 TI - Intestinal microbiome analyses identify melanoma patients at risk for checkpoint blockade-induced colitis. AB - The composition of the intestinal microbiota influences the development of inflammatory disorders. However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota's composition. Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis. Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development. We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis. Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis. Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy. PMID- 26837006 TI - What Is the Clinical Value Associated with Defining Additional Disease-Specific 'Prognostic Indicators'? PMID- 26837005 TI - Metformin prevents the effects of Pseudomonas aeruginosa on airway epithelial tight junctions and restricts hyperglycaemia-induced bacterial growth. AB - Lung disease and elevation of blood glucose are associated with increased glucose concentration in the airway surface liquid (ASL). Raised ASL glucose is associated with increased susceptibility to infection by respiratory pathogens including Staphylococcus aureus and Pseudomonas aeruginosa. We have previously shown that the anti-diabetes drug, metformin, reduces glucose-induced S. aureus growth across in vitro airway epithelial cultures. The aim of this study was to investigate whether metformin has the potential to reduce glucose-induced P. aeruginosa infections across airway epithelial (Calu-3) cultures by limiting glucose permeability. We also explored the effect of P. aeruginosa and metformin on airway epithelial barrier function by investigating changes in tight junction protein abundance. Apical P. aeruginosa growth increased with basolateral glucose concentration, reduced transepithelial electrical resistance (TEER) and increased paracellular glucose flux. Metformin pre-treatment of the epithelium inhibited the glucose-induced growth of P. aeruginosa, increased TEER and decreased glucose flux. Similar effects on bacterial growth and TEER were observed with the AMP activated protein kinase agonist, 5-aminoimidazole-4-carboxamide ribonucleotide. Interestingly, metformin was able to prevent the P. aeruginosa-induced reduction in the abundance of tight junction proteins, claudin-1 and occludin. Our study highlights the potential of metformin to reduce hyperglycaemia-induced P. aeruginosa growth through airway epithelial tight junction modulation, and that claudin-1 and occludin could be important targets to regulate glucose permeability across airway epithelia and supress bacterial growth. Further investigation into the mechanisms regulating metformin and P. aeruginosa action on airway epithelial tight junctions could yield new therapeutic targets to prevent/suppress hyperglycaemia-induced respiratory infections, avoiding the use of antibiotics. PMID- 26837007 TI - Facility characteristics as independent prognostic factors of nursing home acquired pneumonia. AB - BACKGROUND/AIMS: Recently, the incidence of nursing home-acquired pneumonia (NHAP) has been increasing and is now the leading cause of death among nursing home residents. This study was performed to identify risk factors associated with NHAP mortality, focusing on facility characteristics. METHODS: Data on all patients >= 70 years of age admitted with newly diagnosed pneumonia were reviewed. To compare the quality of care in nursing facilities, the following three groups were defined: patients who acquired pneumonia in the community, care homes, and care hospitals. In these patients, 90-day mortality was compared. RESULTS: Survival analyses were performed in 282 patients with pneumonia. In the analyses, 90-day mortality was higher in patients in care homes (12.2%, 40.3%, and 19.6% in community, care homes, and care hospitals, respectively). Among the 118 NHAP patients, residence in a care home, structural lung diseases, treatment with inappropriate antimicrobial agents for accompanying infections, and a high pneumonia severity index score were risk factors associated with higher 90-day mortality. However, infection by potentially drug-resistant pathogens was not important. CONCLUSIONS: Unfavorable institutional factors in care homes are important prognostic factors for NHAP. PMID- 26837008 TI - Everolimus-induced activation of latent Mycobacterium tuberculosis infection in a patient with metastatic renal cell carcinoma. PMID- 26837009 TI - An isolated cardiac relapse after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia. PMID- 26837010 TI - Mild form of Guillain-Barre syndrome in a patient with primary Epstein-Barr virus infection. PMID- 26837011 TI - A rare case of Rosai-Dorfman disease without lymphadenopathy. PMID- 26837013 TI - Correction: Catenane-based mechanically-linked block copolymers. AB - Correction for 'Catenane-based mechanically-linked block copolymers' by B. Nisar Ahamed et al., Chem. Commun., 2016, DOI: . PMID- 26837012 TI - Correlates of online health information-seeking behaviors in a low-income Hispanic community. AB - OBJECTIVE: The purpose of this study was to explore the correlates of online health information-seeking behaviors among Hispanic residents of a low-income urban neighborhood. METHODS: Data were collected with a community survey from 1045 unique participants at ambulatory care clinics in a largely Hispanic immigrant community in northern Manhattan, New York. A descriptive correlational analysis was conducted using logistic regression. RESULTS: A majority of the participants were born outside the United States (85.7%), and half (50.3%) had completed high school. A logistic regression revealed that five independent variables were significantly correlated with online health information-seeking behaviors: age, education, marital status, primary language, and health literacy. Age and Spanish as preferred language were negatively associated with online health information-seeking (OR = 0.93 and 0.50), whereas education and health literacy were positively associated with online health information-seeking (OR = 4.28 and 1.28). CONCLUSIONS: The findings have implications for designing online health information resources and interventions appropriate for the populations they are likely to reach. Furthermore, the findings highlight the need for special efforts to ensure access to reliable health information for immigrant populations and those with low health literacy. PMID- 26837014 TI - Transforaminal epidural steroid injections influence Mechanical Diagnosis and Therapy (MDT) pain response classification in candidates for lumbar herniated disc surgery. AB - STUDY DESIGN: Prospective cohort study. BACKGROUND: Although lumbar radiculopathy is regarded as a specific diagnosis, the most effective treatment strategy is unclear. Commonly used treatments include transforaminal epidural steroid injections (TESIs) and Mechanical Diagnosis & Therapy (MDT), but no studies have investigated the effectiveness of this combination. MDT differentiates pain centralization (C) from non-centralization (NC), which indicates good vs. poor prognostic validity respectively. OBJECTIVE: The main aims were 1) to determine changes in Mechanical Diagnosis and Therapy (MDT) pain response classifications after transforaminal epidural steroid injections (TESIs) in candidates for lumbar herniated disc surgery and 2) to evaluate differences in short and long term outcomes for patients with different pain response classifications. METHODS: Candidates for lumbar herniated disc surgery were assessed with a MDT protocol and their pain response classified as centralizing or peripheralizing. For this study,only patients were eligible who showed a peripheralizing pain response at intake. All patients then received TESIs and were reassessed and classified using the MDT protocol, into groups according to pain response (resolved, centralizing, peripheralizing with less pain and peripheralising with severe pain). After receiving targeted treatment based on pain response after TESIs, ranging from advice, MDT or surgery, follow-up assessments were completed at discharge and at 12 months. The primary outcomes were disability (Roland-Morris Disability Questionnaire [RMDQ] for Sciatica), pain severity in leg (visual analogue scale [VAS], 0-100) and global perceived effect (GPE). Linear mixed-models were used to determine between-groups differences in outcome. RESULTS: A total of 77 patients with lumbar disc herniation and peripheralizing symptoms were included. Patients received an average of 2 (SD 0.7) TESIs. After TESIs, 17 patients (22%) were classified as peripheralizing with continuing severe pain.These patients underwent surgery and were not further evaluated. Eleven (14%) patients were classified as resolved, 37 (48%) as centralizing with significant less pain, and 12 (16%) as peripheralizing with significant less pain. None of these patients underwent surgery. Resolved and centralizer subgroups had better outcomes in terms of VAS and RMDQ than the non-operated peripheralizers at discharge and at 12 months. The succes rates (GPE) for the resolved, centralizing, and peripheralizing with less pain patients were 100%, 100% and 33% respectively at short term, and 100%, 92% and 50% respectively at long term. CONCLUSION: After TESIs, a peripheralizing pain pattern changed to resolved or centralizing in 62% of the patients. For the non-operated patients, those with a centralising pattern after TESIs reported better pain and disability outcomes than those with peripheralizing pattern at short and long term. PMID- 26837015 TI - Relationship between flexion-rotation test and ultrasound thickness measurement of the abdominal muscles. AB - OBJECTIVE: The purpose of this study was to investigate the relationship between flexion-rotation test and ultrasound (US) thickness measurement of the antero lateral abdominal muscles. DESIGN: Following ethical approval, a convenience sample of 55 subjects between the ages of 20 and 30 years participated in this study. Endurance of the abdominal muscles was measured using the flexion-rotation test in all subjects. US thickness measurement for the transversus abdominis (TrA), internal oblique (IO) and external oblique (EO) muscles was performed on the right side at rest in a supine position. RESULTS: Pearson correlation coefficient between the variables of the study showed no significant relationship between the flexion-rotation test and US thickness measurements of the TrA (r = 0.03, P = 0.80), IO (r = -0.13, P = 0.32), and EO (r = -0.14, P = 0.31) muscles. The significance level of 0.05 was chosen. CONCLUSION: It seems that there is no significant relationship between the flexion-rotation test and US measurement of abdominal muscles thickness. PMID- 26837016 TI - Comparison of self and proxy ratings for motor performance of individuals with Parkinson disease. AB - The impact of Parkinson disease (PD) has been examined in recent years by comparing self-ratings by individuals with PD and proxy ratings by caregivers, communication partners, and/or health care providers. However, the existing evidence is mixed with some researchers suggesting perfect agreement between rater groups while others suggesting differences among rater groups for motor performance of individuals with PD. The current study examined self and proxy perception of performance of individuals with PD for six motor characteristics (gait, rigidity, right and left bradykinesia, rest tremors, and perception of physical effort) based on Unified Parkinson Disease Rating Scale (UPDRS) motor tasks. Participants included 20 individuals with PD, 20 communication partners, and a trained rater. The study compared perceptual ratings and corresponding UPDRS scores as well as rater group differences for perceptual motor ratings. A series of Pearson Product Moment Correlations indicated significant relationship only between self-ratings for gait and rest tremors by individuals with PD and corresponding UPDRS scores (p<.05). Further, a multivariate analysis of variance was completed to compare rater group differences. Results indicated significant overestimation of rest tremors by both individuals with PD and communication partners when compared to corresponding ratings by the trained rater. Overall, the study provided evidence for perception deficits among individuals with PD and communication partners regarding motor performance of individuals with PD. Additional studies are needed to further explore the changes in perception abilities of individuals with PD and communication partners with respect to disease duration, disease severity, and other co-morbid factors. PMID- 26837017 TI - Calibration method for high-accuracy measurement of long focal length with Talbot interferometry: comment. AB - In a recent paper [Appl. Opt.51, 2407 (2012)APOPAI0003-693510.1364/AO.51.002407], the authors presented a calibration method for the long focal length Moire fringe measurements to reduce the relative error to less than 0.02%, which was based on two presented results. We tried to reproduce the same results with the information and equations provided but were unsuccessful. PMID- 26837018 TI - Calibration method for high accuracy measurement of long focal length with Talbot interferometry: reply. AB - Thanks to Sukmock Lee for the attention to our paper [Appl. Opt.51, 2407 (2012)APOPAI0003-693510.1364/AO.51.002407], and also for the comment [Appl. Opt.54, 10571 (2015)10.1364/AO.54.010571APOPAI0003-6935]. Two numerical mistakes were pointed out by Lee and they are corrected in this paper. However, these numerical mistakes do not affect the feasibility and precision of this calibration method. Therefore, it cannot be concluded that it is difficult to agree with the calibration method for the long focal length measurements. PMID- 26837019 TI - Beam splitters for p-polarized light using a high-index quarter-wave layer embedded in a low-index cube prism. AB - A high-index quarter-wave layer (QWL) embedded in a low-index cube prism is designed to achieve 50%-50% beam splitting for incident p-polarized light at a 45 degrees angle of incidence. This is accomplished when the ratio of the refractive index of the QWL to that of the prism is n=3.336666. Such a refractive index ratio is realized, e.g., with a Ge QWL embedded in a LiF cube at 8.357 MUm wavelength. Spectral, angular, and film-thickness sensitivities of this mid-IR beam splitter (BS) are presented. Free-standing QWL pellicles of GaP and GaAs can also function as 50%-50% BSs for incident p-polarized light at 45 degrees at visible and IR wavelengths of 0.610 MUm and 2.929 MUm, respectively. An application in interferometry is briefly discussed. PMID- 26837020 TI - Real-time measurement of temperature variation during nanosecond pulsed-laser induced contamination deposition. AB - In this paper, a study of heat generation during UV laser-induced contamination (LIC) and potentially resulting subsequent thermal damage are presented. This becomes increasingly interesting when optics with delicate coatings are involved. During LIC, radiation can interact with outgassing molecules, both in the gas phase and at the surface, thus triggering chemical and photo-fixation reactions. This is a major hazard, in particular for laser units operating under vacuum conditions such as in space applications. The intense photon flux not only affects the contaminant deposition rate but also alters their chemical structure, which can increase their absorption coefficient. Over cumulative irradiation shots, these molecules formed deposits that increasingly absorb photons and produce heat as a by-product of de-excitation, eventually leading to thermal damage. One could better assess the risk of the latter with the knowledge of temperature during the contamination process. For this purpose, a thermoreflectance technique is used here to estimate the temperature variation from pulse to pulse during contamination deposition through the analysis of a temperature-dependent surface reflectance signal. PMID- 26837021 TI - Real-time pattern recognition using an optical generalized Hough transform. AB - We present some pattern recognition applications of a generalized optical Hough transform and the temporal multiplexing strategies for dynamic scale and orientation-variant detection. Unlike computer-based implementations of the Hough transform, in principle its optical implementation does not impose restrictions on the execution time or on the resolution of the images or frame rate of the videos to be processed, which is potentially useful for real-time applications. Validation experiments are presented. PMID- 26837022 TI - Multiwavelength interferometry system for the Orion laser facility. AB - We report on the design and testing of a multiwavelength interferometry system for the Orion laser facility based upon the use of self-path matching Wollaston prisms. The use of UV corrected achromatic optics allows for both easy alignment with an eye-safe light source and small (~ millimeter) offsets to the focal lengths between different operational wavelengths. Interferograms are demonstrated at wavelengths corresponding to first, second, and fourth harmonics of a 1054 nm Nd:glass probe beam. Example data confirms the broadband achromatic capability of the imaging system with operation from the UV (263 nm) to visible (527 nm) and demonstrates that features as small as 5 MUm can be resolved for object sizes of 15 by 10 mm. Results are also shown for an off-harmonic wavelength that will underpin a future capability. The primary optics package is accommodated inside the footprint of a ten-inch manipulator to allow the system to be deployed from a multitude of viewing angles inside the 4 m diameter Orion target chamber. PMID- 26837023 TI - Nonuniformity correction of imaging systems with a spatially nonhomogeneous radiation source. AB - We present a novel method of nonuniformity correction of imaging systems in a wide optical spectral range by applying a radiation source with an unknown and spatially nonhomogeneous radiance or radiance temperature distribution. The benefit of this method is that it can be applied with radiation sources of arbitrary spatial radiance or radiance temperature distribution and only requires the sufficient temporal stability of this distribution during the measurement process. The method is based on the recording of several (at least three) images of a radiation source and a purposeful row- and line-shift of these sequent images in relation to the first primary image. The mathematical procedure is explained in detail. Its numerical verification with a source of a predefined nonhomogenous radiance distribution and a thermal imager of a predefined nonuniform focal plane array responsivity is presented. PMID- 26837024 TI - Unified direct and coherent orthogonal frequency division multiplexing optical transmission scheme. AB - We experimentally demonstrate a novel unified direct and coherent orthogonal frequency division multiplexing (OFDM) scheme. This self-coherent OFDM scheme simplifies receiver architecture and provides interchangeability between direct and coherent receivers using the same unified transmitter. We have experimentally verified the resilience of this scheme to fiber nonlinearities and achieved receiver sensitivity improvement of up to 1.73 dB as compared to the conventional intensity modulation and direct detection OFDM scheme. We have also verified the effectiveness of a dual-analyzer-based balanced detection scheme. PMID- 26837025 TI - Switching from electromagnetically induced absorption grating to electromagnetically induced phase grating in a closed-loop atomic system. AB - The electromagnetically induced grating is investigated in a four-level double V type quantum system. It is shown that the electromagnetically induced transparency established by the cross-Kerr nonlinear effect can be canceled by the four-wave mixing in a closed-loop atomic system and that the diffraction of the probe beam depends on the relative phase of the applied fields and can be controlled by this parameter. We find that an additional nonlinear contribution is established in the medium response by applying a microwave field to the system and that the electromagnetically induced absorption grating turns to the electromagnetically induced phase grating. This contribution leads to 100% diffraction efficiency in the first-order direction, so we can say that the proposed grating could be considered as a special candidate for the optical networking and communication. PMID- 26837026 TI - Overview of transparent optical ceramics for high-energy lasers at NRL: publisher's note. AB - This note amends the author list of a recent publication [Appl. Opt.54, F210 (2015)]. PMID- 26837027 TI - Confidence intervals for the encircled energy fraction and the half-energy width. AB - The encircled energy fraction and its quantiles, notably the half-energy width, are routinely used to characterize the quality of x-ray optical systems. They are, however, always quoted without a statistical error. We show how nonparametric statistical methods can be used to redress this situation, and we discuss how the knowledge of the statistical error can be used to speed up the characterization efforts for future x-ray observatories. PMID- 26837028 TI - Formation of holographic polymer-dispersed liquid crystal memory by angle multiplexing recording for optically reconfigurable gate arrays. AB - Formation of holographic polymer-dispersed liquid crystal (HPDLC) memory for an optically reconfigurable gate array is discussed for angle-multiplexing recording by controlling the laser interference exposure in LC composites. The successive laser illumination system to record the various configuration contexts at the specified region and angle in HPDLC memory is constructed by using the combination of a half-mirror and a photomask placed on the motorized stages under the control of a personal computer. The effect of laser exposure energy on the formation of holographic memory is investigated by measuring diffraction intensity as a function of exposure energy during the grating formation process and observing the internal grating structure by scanning electron microscopy. The optical reconfiguration in the gate-array VLSI is executed for configuration contexts of OR and NOR operations shown as logical operators that are reconstructed by laser irradiation at different incident angles for a specified region in the HPDLC memory. PMID- 26837029 TI - Effect of surface cleaning on spectral response for InGaAs photocathodes. AB - Photocathode surface treatment aims to obtain high sensitivity, where the key point is to acquire an atomically clean surface. Various surface cleaning methods for removing contamination from InGaAs photocathode surfaces were investigated. The atomic compositions of InGaAs photocathode structures and surfaces were measured by x-ray photoelectron spectroscopy and Ar ion sputtering. After surface cleaning, the InGaAs surface is arsenoxide-free, however, a small amount of Ga2O3 and In2O3 still can be found. The 1:1 mixed solution of hydrochloric acid to deionized water followed by thermal annealing at 525 degrees C has been demonstrated to be the best choice in dealing with the surface oxides. After the Cs/O activation, a surface model was proposed where the oxides on the surface will lead to a positive electron affinity, adversely affecting low-energy electrons escaping to the vacuum, which is reflected by the photocurrent curves and the spectral response curves. PMID- 26837030 TI - Spectral characterization of nanostructured birefringent porous silicon. AB - We present measurements and analysis of the reflection spectrum of white light from a highly birefringent porous silicon layer at different polarization states. We report an anomalous pattern in the spectrum of linearly polarized light at 45 degrees with respect to the principal axes of the layer. This spectrum comprises a combination of two interference effects, namely the Fabry-Perot-type multiple beam interference present in a simple thin film, and a two-wave interference caused by the beat of two combined orthogonally polarized waves propagating in the birefringent medium. We perform a Fourier analysis of the measured reflected spectra. This analysis furnishes a powerful tool in order to separate the two interference mechanisms and determine the degree of coherence of their superposition. PMID- 26837032 TI - Optical compression and encryption system combining multiple measurement matrices with fractional Fourier transform. AB - Optical cryptosystems combined with compressed sensing can achieve compression and encryption simultaneously. But they usually use the same measurement matrix to sample all blocks of an image, which makes it easy to estimate the measurement matrix in the chosen plaintext attack. In this paper, we propose a robust scheme adopting multiple measurement matrices to overcome this shortcoming. The matrices can be efficiently derived by applying random row exchanging to a basic one, which is also encoded into the fractional Fourier transform (FrFT) domain to improve the visual effect of wrongly decrypted images. Chaos-based pixel scrambling is added into our double FrFT cryptosystem to guarantee its nonlinearity. Simulation results have shown the security and effectiveness of our scheme. PMID- 26837031 TI - Generation of arbitrary order Bessel beams via 3D printed axicons at the terahertz frequency range. AB - We present the generation of arbitrary order Bessel beams at 0.3 THz through the implementation of suitably designed axicons based on 3D printing technology. The helical axicons, which possess thickness gradients in both radial and azimuthal directions, can convert the incident Gaussian beam into a high-order Bessel beam with spiral phase structure. The evolution of the generated Bessel beams are characterized experimentally with a three-dimensional field scanner. Moreover, the topological charges carried by the high-order Bessel beams are determined by the fork-like interferograms. This 3D-printing-based Bessel beam generation technique is useful not only for THz imaging systems with zero-order Bessel beams but also for future orbital-angular-momentum-based THz free-space communication with higher-order Bessel beams. PMID- 26837033 TI - Ratiometric optical fiber sensor for dual sensing of copper ion and dissolved oxygen. AB - This paper develops a new ratiometric optical dual sensor for Cu2+ ions and dissolved oxygen (DO) incorporating a sol-gel matrix doped with palladium tetrakis pentafluorophenyl porphine as the oxygen-sensitive material, CdSe quantum dots as the Cu2+ ion-sensing material, and 7-amino-4-trifluoromethyl coumarin as the Cu2+ /DO practically independent fluorescent dye. The feasibility of coating an optical fiber with the sensing film to fabricate a ratiometric optical fiber dual sensor is investigated. Using an LED with a central wavelength of 405 nm as an excitation source, it is shown that the emission wavelengths of the Cu2+ ion-sensitive, DO-sensitive dye and the reference dye have no spectral overlap and therefore permit Cu2+ ion and DO concentration to be measured using a ratiometric-based method. The ratiometric optical fiber dual sensor has been tested with regard to monitoring different Cu2+ ion (0-10 MUM) and DO concentrations (0-38 mg/L). The results show that the luminescence properties of the Cu2+ ion sensor are independent of the presence of the oxygen sensor and have a uniquely good linear response in the 0-10 MUM range. The proposed ratiometric sensing approach presented in this study has the advantage of suppressing spurious fluctuations in the intensity of the excitation source. PMID- 26837034 TI - Robust modeling and performance analysis of high-power diode side-pumped solid state laser systems. AB - In this paper, we present an enhanced high-power extrinsic diode side-pumped solid-state laser (DPSSL) model to accurately predict the dynamic operations and pump distribution under different practical conditions. We introduce a new implementation technique for the proposed model that provides a compelling incentive for the performance assessment and enhancement of high-power diode side pumped Nd:YAG lasers using cooperative agents and by relying on the MATLAB, GLAD, and Zemax ray tracing software packages. A large-signal laser model that includes thermal effects and a modified laser gain formulation and incorporates the geometrical pump distribution for three radially arranged arrays of laser diodes is presented. The design of a customized prototype diode side-pumped high-power laser head fabricated for the purpose of testing is discussed. A detailed comparative experimental and simulation study of the dynamic operation and the beam characteristics that are used to verify the accuracy of the proposed model for analyzing the performance of high-power DPSSLs under different conditions are discussed. The simulated and measured results of power, pump distribution, beam shape, and slope efficiency are shown under different conditions and for a specific case, where the targeted output power is 140 W, while the input pumping power is 400 W. The 95% output coupler reflectivity showed good agreement with the slope efficiency, which is approximately 35%; this assures the robustness of the proposed model to accurately predict the design parameters of practical, high power DPSSLs. PMID- 26837035 TI - Simultaneous measurement of strain and temperature by two peanut tapers with embedded fiber Bragg grating. AB - A compact optical fiber sensor for simultaneous measurement of strain and temperature is designed and experimentally investigated. The proposed sensor consists of a two-peanut-taper Mach-Zehnder interferometer (MZI) and in-line embedded fiber Bragg grating (FBG). The sensor at a length of 35 mm presents strain sensitivities 1.07 pm/MUepsilon and 0.891 pm/MUepsilon, the temperature sensitivities are 55.35 pm/ degrees C and 10.85 pm/ degrees C, for MZI and FBG, respectively. Through tapering the center of the sensor by a fusion splicer, the strain sensitivity of the MZI is improved to 1.93 pm/MUepsilon. The resolutions for strain and temperature measurement are +/-3.104 MUepsilon and +/-0.194 degrees C with the wavelength resolution of 5 pm. The experimental results show that the sensor is able to simultaneously measure strain and temperature by sensitivity matrix with advantages such as simple structure, compact size, ease of fabrication, low cost, etc. PMID- 26837036 TI - Multiwavelength depth encoding method for 3D range geometry compression. AB - This paper presents a novel method for representing three-dimensional (3D) range data within regular two-dimensional (2D) images using multiwavelength encoding. These 2D images can then be further compressed using traditional lossless (e.g., PNG) or lossy (e.g., JPEG) image compression techniques. Current 3D range data compression methods require significant filtering to reduce lossy compression artifacts. The nature of the proposed encoding, however, offers a significant level of robustness to such artifacts brought about by high levels of JPEG compression. This enables extremely high compression ratios while maintaining a very low reconstruction error percentage with little to no filtering required to remove compression artifacts. For example, when encoding 3D geometry with the proposed method and storing the resulting 2D image with Matlab R2014a JPEG80 image compression, compression ratios of approximately 935:1 versus the OBJ format can be achieved at an error rate of approximately 0.027% without any filtering. PMID- 26837037 TI - Retina-like sensor based on a lens array with a large field of view. AB - This paper puts forward a retina-like sensor based on a lens array, which can be used in conventional optical systems. This sensor achieves log-polar mapping by dividing the imaging optical system's image plane using a lens array. In this paper the mathematical model has been set up with the relative structural parameters. Also, the simulation experiments and parameter analysis have been discussed to verify the reliability of this system. From the experiment results, it can be seen that this sensor realized the log-polar mapping with the transformed image output. Each lens corresponded to a circular region in the image plane with no crossover between different fields of view of adjacent lenses. When the number of rings changed, the relative error did not significantly change, and this error could be reduced to 1% when the number of lenses in each ring was increased. The work widely enlarged the application of this kind of sensor, which will lay a theoretical foundation for retina-like sensors. PMID- 26837038 TI - Electrically actuated phase-change pixels for transmissive and reflective spatial light modulators in the near and mid infrared. AB - Transmissive and reflective spatial light modulators have been designed and simulated for the 1.55 to 2.10 MUm spectral region. An electrically actuated layer of phase-change material (PCM) was employed as the electro-optical medium for two-state self-holding "light-to-dark" intensity modulation of free-space light beams. The PCM was sandwiched between transparent conductive N-doped Si or indium tin oxide contact layers in a simple planar structure. A 100 to 500 nm PCM layer of Ge2Sb2Te5 (GST) was employed for optimum performance at 1.55 MUm where the transmissive-modulator insertion loss was around 4.5 dB. The GST light-dark contrast was found to be 32 dB. For the GST reflection device, an included metal film (Ag) improved the 1.55 MUm performance metrics to 0.7 dB of insertion loss with a contrast around 26 dB. The calculated performance for both types of spatial light modulators was robust to changes in the input incidence angle near normal incidence. Applications include infrared scene generation and signal processing. PMID- 26837039 TI - Spectral supralinearity prediction of silicon photodiodes in the near-infrared range. AB - A model describing spectral supralinearity for a silicon photodiode in the near infrared region is presented. This theoretical model is based on the internal quantum efficiency model of the photodiode using Shockley-Read-Hall recombination, which depends on the inner structure parameters of the photodiodes. Comparing the experimental results with the theoretical calculation results, the model enables us to quantitatively predict the starting power level, shape, and wavelength dependence of the supralinearity for a silicon photodiode. This model contributes to high-accuracy measurements over wide optical power ranges and various incident wavelengths. PMID- 26837040 TI - Multiple-wavelength double random phase encoding with CCD-plane sparse-phase multiplexing for optical information verification. AB - A novel method is proposed by using multiple-wavelength double random phase encoding (MW-DRPE) with CCD-plane sparse-phase multiplexing for optical information verification. Two different strategies are applied to conduct sparse phase multiplexing in the CCD plane. The results demonstrate that large capacity can be achieved for optical multiple-image verification. The proposed optical verification strategy is implemented based on optical encoding, and the keys generated by optical encryption can further guarantee the safety of the designed optical multiple-image verification system. The proposed method provides a novel alternative for DRPE-based optical information verification. PMID- 26837041 TI - Carrier-envelope phase changes in the focal region: propagation effects measured by spectral interferometry. AB - Spectral interferometric measurements are presented that show how wave propagation affects the carrier-envelope phase (CEP) of an ultrashort pulse in the focal region and results in variations that are different from the Gouy phase shift. Wavelength-dependent properties of the input beam are investigated and are seen to influence how the CEP is altered. The measured CEP changes show characteristics similar to the variations predicted by theory. PMID- 26837042 TI - Autophagy in motor neuron disease: Key pathogenetic mechanisms and therapeutic targets. AB - Autophagy is a lysosome-dependant intracellular degradation process that eliminates long-lived proteins as well as damaged organelles from the cytoplasm. An increasing body of evidence suggests that dysregulation of this system plays a pivotal role in the etiology and/or progression of neurodegenerative diseases including motor neuron disorders. Herein, we review the latest findings that highlight the involvement of autophagy in the pathogenesis of amyotrophic lateral sclerosis (ALS) and the potential role of this pathway as a target of therapeutic purposes. Autophagy promotes the removal of toxic, cytoplasmic aggregate-prone pathogenetic proteins, enhances cell survival, and modulates inflammation. The existence of several drugs targeting this pathway can facilitate the translation of basic research to clinical trials for ALS and other motor neuron diseases. PMID- 26837043 TI - The microtubular cytoskeleton of olfactory neurons derived from patients with schizophrenia or with bipolar disorder: Implications for biomarker characterization, neuronal physiology and pharmacological screening. AB - Schizophrenia (SZ) and Bipolar Disorder (BD) are highly inheritable chronic mental disorders with a worldwide prevalence of around 1%. Despite that many efforts had been made to characterize biomarkers in order to allow for biological testing for their diagnoses, these disorders are currently detected and classified only by clinical appraisal based on the Diagnostic and Statistical Manual of Mental Disorders. Olfactory neuroepithelium-derived neuronal precursors have been recently proposed as a model for biomarker characterization. Because of their peripheral localization, they are amenable to collection and suitable for being cultured and propagated in vitro. Olfactory neuroepithelial cells can be obtained by a non-invasive brush-exfoliation technique from neuropsychiatric patients and healthy subjects. Neuronal precursors isolated from these samples undergo in vitro the cytoskeletal reorganization inherent to the neurodevelopment process which has been described as one important feature in the etiology of both diseases. In this paper, we will review the current knowledge on microtubular organization in olfactory neurons of patients with SZ and with BD that may constitute specific cytoskeletal endophenotypes and their relation with alterations in L-type voltage-activated Ca(2+) currents. Finally, the potential usefulness of neuronal precursors for pharmacological screening will be discussed. PMID- 26837044 TI - The brain interstitial system: Anatomy, modeling, in vivo measurement, and applications. AB - Although neurons attract the most attention in neurobiology, our current knowledge of neural circuit can only partially explain the neurological and psychiatric conditions of the brain. Thus, it is also important to consider the influence of brain interstitial system (ISS), which refers to the space among neural cells and capillaries. The ISS is the major compartment of the brain microenvironment that provides the immediate accommodation space for neural cells, and it occupies 15% to 20% of the total brain volume. The brain ISS is a dynamic and complex space connecting the vascular system and neural networks and it plays crucial roles in substance transport and signal transmission among neurons. Investigation of the brain ISS can provide new perspectives for understanding brain architecture and function and for exploring new strategies to treat brain disorders. This review discussed the anatomy of the brain ISS under both physiological and pathological conditions, biophysical modeling of the brain ISS and in vivo measurement and imaging techniques, including recent findings on brain ISS divisions. Moreover, the implications of ISS knowledge for basic neuroscience and clinical applications are addressed. PMID- 26837046 TI - Left caloric vestibular stimulation as a tool to reveal implicit and explicit parameters of body representation. AB - Homeostatic parameters, such as temperature, are related to body representation. In this study, we measured whether caloric vestibular stimulation (CVS) alters body temperature and tactile processing, and if in the direction predicted by a holistic body matrix representation. Skin temperature and tactile two-point discrimination (TPD) acuity were measured for both arms before, immediately after and with a delay from CVS. Participants were also administered a personality questionnaire and an anxiety inventory to rule out confounding factors. Two control experiments were planned to exclude casual variations. Our results show that temperature drops significantly in both arms after CVS. CVS also induces a bilateral improvement in tactile acuity (even though not immediately after but in the delayed condition). Finally, these effects are not due to learning, as demonstrated by the control experiment. In summary, our results suggest that vestibular stimulation updates body representation, supporting the evidence in favor of a body matrix. PMID- 26837047 TI - Unconscious vision spots the animal but not the dog: Masked priming of natural scenes. AB - The functional role of consciousness has been traditionally assumed to be related to high-level executive functions, but recent theories of visual consciousness suggest qualitative differences between conscious and unconscious processes also in lower level visual processes. We tested how specific is the information that can be extracted by unconscious processes from natural scenes. Prime images which were suppressed from consciousness by continuous flash suppression facilitated categorization of visible targets at superordinate level (animal vs. non-animal) when the prime shared a category membership with the target. Suppressed prime images did not have any effect on categorization at the basic level (e.g., horse vs. other animal). Priming occurred at basic level categorization only when the prime images were available to consciousness. This pattern supports a "coarse-to fine" model in which the visual system can unconsciously access coarse representations, but consciousness is needed for finer analysis of visual scenes. PMID- 26837045 TI - Identifying ligands at orphan GPCRs: current status using structure-based approaches. AB - GPCRs are the most successful pharmaceutical targets in history. Nevertheless, the pharmacology of many GPCRs remains inaccessible as their endogenous or exogenous modulators have not been discovered. Tools that explore the physiological functions and pharmacological potential of these 'orphan' GPCRs, whether they are endogenous and/or surrogate ligands, are therefore of paramount importance. Rates of receptor deorphanization determined by traditional reverse pharmacology methods have slowed, indicating a need for the development of more sophisticated and efficient ligand screening approaches. Here, we discuss the use of structure-based ligand discovery approaches to identify small molecule modulators for exploring the function of orphan GPCRs. These studies have been buoyed by the growing number of GPCR crystal structures solved in the past decade, providing a broad range of template structures for homology modelling of orphans. This review discusses the methods used to establish the appropriate signalling assays to test orphan receptor activity and provides current examples of structure-based methods used to identify ligands of orphan GPCRs. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc. PMID- 26837048 TI - Crystal structure of the nucleosome containing ultraviolet light-induced cyclobutane pyrimidine dimer. AB - The cyclobutane pyrimidine dimer (CPD) is induced in genomic DNA by ultraviolet (UV) light. In mammals, this photolesion is primarily induced within nucleosomal DNA, and repaired exclusively by the nucleotide excision repair (NER) pathway. However, the mechanism by which the CPD is accommodated within the nucleosome has remained unknown. We now report the crystal structure of a nucleosome containing CPDs. In the nucleosome, the CPD induces only limited local backbone distortion, and the affected bases are accommodated within the duplex. Interestingly, one of the affected thymine bases is located within 3.0 A from the undamaged complementary adenine base, suggesting the formation of complementary hydrogen bonds in the nucleosome. We also found that UV-DDB, which binds the CPD at the initial stage of the NER pathway, also efficiently binds to the nucleosomal CPD. These results provide important structural and biochemical information for understanding how the CPD is accommodated and recognized in chromatin. PMID- 26837049 TI - Aquaporin-9 facilitates membrane transport of hydrogen peroxide in mammalian cells. AB - Aquaporin (AQP) 9, a member of the transmembrane water channel family, is defined as a water/glycerol transporting protein. Some AQPs including AQP3 and AQP8 have been recently found to transport hydrogen peroxide (H2O2). Here we show that AQP9 facilitates the membrane transport of H2O2 in human and mice cells. Enforced expression of human AQP9 in Chinese hamster ovary-K1 potentiated the increase in cellular H2O2 after adding exogenous H2O2. In contrast, AQP9 knockdown by siRNA in human hepatoma HepG2 cells reduced the import of extracellular H2O2. In addition, the uptake of extracellular H2O2 was suppressed in erythrocytes and bone marrow-derived mast cells from AQP9 knockout mice compared with wild-type cells. Coincidentally, H2O2-induced cytotoxicity was attenuated by AQP9 deficiency in human and mice cells. Our findings implicate the involvement of AQP9 in H2O2 transport in human and mice cells. PMID- 26837050 TI - The absence of intraband scattering in a consistent theory of Gilbert damping in pure metallic ferromagnets. AB - Damping of magnetization dynamics in a ferromagnetic metal, arising from spin orbit coupling, is usually characterised by the Gilbert parameter alpha. Recent calculations of this quantity, using a formula due to Kambersky, find that it is infinite for a perfect crystal owing to an intraband scattering term which is of third order in the spin-orbit parameter xi. This surprising result conflicts with recent work by Costa and Muniz who study damping numerically by direct calculation of the dynamical transverse susceptibility in the presence of spin orbit coupling. We resolve this inconsistency by following the approach of Costa and Muniz for a slightly simplified model where it is possible to calculate alpha analytically. We show that to second order in xi one retrieves the Kambersky result for alpha, but to higher order one does not obtain any divergent intraband terms. The present work goes beyond that of Costa and Muniz by pointing out the necessity of including the effect of long-range Coulomb interaction in calculating damping for large xi. A direct derivation of the Kambersky formula is given which shows clearly the restriction of its validity to second order in xi so that no intraband scattering terms appear. This restriction has an important effect on the damping over a substantial range of impurity content and temperature. The experimental situation is discussed. PMID- 26837052 TI - Effects of Apremilast on Pruritus and Skin Discomfort/Pain Correlate With Improvements in Quality of Life in Patients With Moderate to Severe Plaque Psoriasis. AB - Pruritus and skin discomfort/pain negatively impact health-related quality of life (HRQoL). The effects of apremilast, an oral phosphodiesterase inhibitor, on pruritus, skin discomfort/pain, and patient global assessment of psoriasis disease activity (PgAPDA) were assessed in moderate/severe chronic plaque psoriasis patients in the phase 3 ESTEEM trials. Significant improvements in pruritus and skin discomfort/pain observed at Week 2 with apremilast versus placebo (both studies, p < 0.0001) were sustained through Week 32. Among apremilast-treated patients, improvements in pruritus visual analog scale (VAS) scores correlated with Dermatology Life Quality Index scores (rs = 0.55 [Week 16], rs>=0.51 [Week 32]; both studies, p < 0.001). PgAPDA correlated with improvements in pruritus (rs>=0.56 [Week 16]; rs>=0.53 [Week 32]; both studies, p < 0.001) and skin discomfort/pain (rs >=0.54 [Week 16]; rs>=0.53 [Week 32]; both studies, p < 0.001) VAS scores. Apremilast provided rapid and sustained improvement in pruritus and skin discomfort/pain, symptoms not typically captured in psoriasis assessments (e.g., PASI) that contribute significantly to patients' disease severity and HRQoL perceptions. PMID- 26837051 TI - Genetically defined autoinflammatory diseases. AB - Autoinflammatory diseases are hyperinflammatory, immune dysregulatory conditions that typically present in early childhood with fever and rashes and disease specific patterns of organ inflammation. This review provides a historic background of autoinflammatory disease research, an overview of the currently genetically defined autoinflammatory diseases, and insights into treatment strategies derived from understanding of the disease pathogenesis. The integrative assessment of autoinflammatory conditions led to the identification of innate pro-inflammatory cytokine 'amplification loops' as the cause of the systemic and organ-specific disease manifestations, which initially centered around increased IL-1 production and signaling. More recently, additional innate pro-inflammatory cytokine amplification loops resulting in increased Type I IFN, IL-17, IL-18, or IL-36 signaling or production have led to the successful use of targeted therapies in some of these conditions. Clinical findings such as fever patterns, type of skin lesions, genetic mutation testing, and the prevalent cytokine abnormalities can be used to group autoinflammatory diseases. PMID- 26837053 TI - Nickel-Catalyzed Decarboxylative Difluoroalkylation of alpha,beta-Unsaturated Carboxylic Acids. AB - The first example of nickel-catalyzed decarboxylative fluoroalkylation of alpha,beta-unsaturated carboxylic acids has been developed with commonly available fluoroalkyl halides. This novel transformation has demonstrated broad substrate scope, excellent functional-group tolerance, mild reaction conditions, and excellent stereoselectivity. Mechanistic investigations indicate that a fluoroalkyl radical is involved in the catalytic cycle. PMID- 26837055 TI - Acute liver injury and acute liver failure from mushroom poisoning in North America. AB - BACKGROUND & AIMS: Published estimates of survival associated with mushroom (amatoxin)-induced acute liver failure (ALF) and injury (ALI) with and without liver transplant (LT) are highly variable. We aimed to determine the 21-day survival associated with amatoxin-induced ALI (A-ALI) and ALF (A-ALF) and review use of targeted therapies. METHODS: Cohort study of all A-ALI/A-ALF patients enrolled in the US ALFSG registry between 01/1998 and 12/2014. RESULTS: Of the 2224 subjects in the registry, 18 (0.8%) had A-ALF (n = 13) or A-ALI (n = 5). At admission, ALF patients had higher lactate levels (5.2 vs. 2.2 mm, P = 0.06) compared to ALI patients, but INR (2.8 vs. 2.2), bilirubin (87 vs. 26 MUm) and MELD scores (28 vs. 24) were similar (P > 0.2 for all). Of the 13 patients with ALF, six survived without LT (46%), five survived with LT (39%) and two died without LT (15%). Of the five patients with ALI, four (80%) recovered and one (20%) survived post-LT. Comparing those who died/received LT (non-spontaneous survivors [NSS]) with spontaneous survivors (SS), N-acetylcysteine was used in nearly all patients (NSS 88% vs. SS 80%); whereas, silibinin (25% vs. 50%), penicillin (50% vs. 25%) and nasobiliary drainage (0 vs. 10%) were used less frequently (P > 0.15 for all therapies). CONCLUSION: Patients with mushroom poisoning with ALI have favourable survival, while around half of those presenting with ALF may eventually require LT. Further study is needed to define optimal management (including the use of targeted therapies) to improve survival, particularly in the absence of LT. PMID- 26837056 TI - Likelihood ratio meta-analysis: New motivation and approach for an old method. AB - A 95% confidence interval (CI) in an updated meta-analysis may not have the expected 95% coverage. If a meta-analysis is simply updated with additional data, then the resulting 95% CI will be wrong because it will not have accounted for the fact that the earlier meta-analysis failed or succeeded to exclude the null. This situation can be avoided by using the likelihood ratio (LR) as a measure of evidence that does not depend on type-1 error. We show how an LR-based approach, first advanced by Goodman, can be used in a meta-analysis to pool data from separate studies to quantitatively assess where the total evidence points. The method works by estimating the log-likelihood ratio (LogLR) function from each study. Those functions are then summed to obtain a combined function, which is then used to retrieve the total effect estimate, and a corresponding 'intrinsic' confidence interval. Using as illustrations the CAPRIE trial of clopidogrel versus aspirin in the prevention of ischemic events, and our own meta-analysis of higher potency statins and the risk of acute kidney injury, we show that the LR based method yields the same point estimate as the traditional analysis, but with an intrinsic confidence interval that is appropriately wider than the traditional 95% CI. The LR-based method can be used to conduct both fixed effect and random effects meta-analyses, it can be applied to old and new meta-analyses alike, and results can be presented in a format that is familiar to a meta-analytic audience. PMID- 26837057 TI - Epigenetic divergence as a potential first step in darter speciation. AB - Recent studies show that epigenetic variation in the form of DNA methylation may serve as a substrate for selection. Theory suggests that heritable epigenetic marks that increase fitness should increase in frequency in a population, and these changes may result in novel morphology, behaviour, or physiology, and ultimately reproductive isolation. Therefore, epigenetic variation might provide the first substrate for selection during the course of evolutionary divergence. This hypothesis predicts that populations in the earliest stages of divergence will differentiate in their methylome prior to any genetic differentiation. While several studies have investigated natural epigenetic variation, empirical studies that test predictions about its role in speciation are surprisingly scarce. Here, we investigate DNA methylation variation using an isoschizomeric digest method, Methyl-Sensitive Amplified Polymorphism, across multiple stages of evolutionary divergence in natural populations of North American stream fishes. We show that epigenetic differentiation between methylomes is greater than genetic divergence among closely related populations across two river drainages. Additionally, we demonstrate that epigenetic divergence is a stronger predictor of the strength of behavioural reproductive isolation and suggest that changes in the methylome could influence the evolution of reproductive isolation between species. Our findings suggest a role for epigenetics not only in the initiation of divergence, but also in the maintenance of species boundaries over greater evolutionary timescales. PMID- 26837058 TI - Update on the role of plasmacytoid dendritic cells in inflammatory/autoimmune skin diseases. AB - Plasmacytoid dendritic cells (pDCs) represent a specialized dendritic cell population that exhibit plasma cell morphology, express CD4, CD123, blood-derived dendritic cell antigen-2 (BDCA-2) and Toll-like receptor (TLR)7 and TLR9 within endosomal compartments. When activated, pDCs are capable of producing large quantities of type I IFNs (mainly IFN-alpha/beta), which provide antiviral resistance and link the innate and adaptive immunity. While generally lacking from normal skin, pDCs infiltrate the skin and appear to be involved in the pathogenesis of several inflammatory, infectious (especially viral) and neoplastic entities. In recent years, pDC role in inflammatory/autoimmune skin conditions has been extensively studied. Unlike type I IFN-mediated protective immunity that pDCs provide at the level of the skin by regulated sensing of microbial or self-nucleic acids upon skin damage, excessive sensing may elicit IFN-driven inflammatory/autoimmune diseases. In this review, focus will be on the role of pDCs in cutaneous inflammatory/autoimmune dermatoses. PMID- 26837054 TI - Point-of-care diagnostics for niche applications. AB - Point-of-care or point-of-use diagnostics are analytical devices that provide clinically relevant information without the need for a core clinical laboratory. In this review we define point-of-care diagnostics as portable versions of assays performed in a traditional clinical chemistry laboratory. This review discusses five areas relevant to human and animal health where increased attention could produce significant impact: veterinary medicine, space travel, sports medicine, emergency medicine, and operating room efficiency. For each of these areas, clinical need, available commercial products, and ongoing research into new devices are highlighted. PMID- 26837059 TI - Upregulation of granzyme B and interferon-gamma mRNA in responding lesions by treatment with nivolumab for metastatic melanoma: a case report. PMID- 26837061 TI - In vivo observation of quadrupolar splitting in (39)K magnetic resonance spectroscopy of human muscle tissue. AB - The purpose of this work was to explore the origin of oscillations of the T(*)2 decay curve of (39)K observed in studies of (39)K magnetic resonance imaging of the human thigh. In addition to their magnetic dipole moment, spin-3/2 nuclei possess an electric quadrupole moment. Its interaction with non-vanishing electrical field gradients leads to oscillations in the free induction decay and to splitting of the resonance. All measurements were performed on a 7T whole-body MRI scanner (MAGNETOM 7T, Siemens AG, Erlangen, Germany) with customer-built coils. According to the theory of quadrupolar splitting, a model with three Lorentzian-shaped peaks is appropriate for (39)K NMR spectra of the thigh and calf. The frequency shifts of the satellites depend on the angle between the calf and the static magnetic field. When the leg is oriented parallel to the static magnetic field, the satellites are shifted by about 200 Hz. In the thigh, rank-2 double quantum coherences arising from anisotropic quadrupolar interaction are observed by double-quantum filtration with magic-angle excitation. In addition to the spectra, an image of the thigh with a nominal resolution of (16 * 16 * 32) mm(3) was acquired with this filtering technique in 1:17 h. From the line width of the resonances, (39)K transverse relaxation time constants T(*)2, fast = (0.51 +/- 0.01) ms and T(*)2, slow = (6.21 +/- 0.05) ms for the head were determined. In the thigh, the left and right satellite, both corresponding to the short component of the transverse relaxation time constant, take the following values: T(*)2, fast = (1.56 +/- 0.03) ms and T(*)2, fast = (1.42 +/- 0.03) ms. The centre line, which corresponds to the slow component, is T(*)2, slow = (9.67 +/- 0.04) ms. The acquisition time of the spectra was approximately 10 min. Our results agree well with a non-vanishing electrical field gradient interacting with (39)K nuclei in the intracellular space of muscle tissue. PMID- 26837062 TI - Mechanistic Insights into the Radical S-adenosyl-l-methionine Enzyme NosL From a Substrate Analogue and the Shunt Products. AB - The radical S-adenosyl-l-methionine (SAM) enzyme NosL catalyzes the transformation of l-tryptophan into 3-methyl-2-indolic acid (MIA), which is a key intermediate in the biosynthesis of a clinically interesting antibiotic nosiheptide. NosL catalysis was investigated by using the substrate analogue 2 methyl-3-(indol-3-yl)propanoic acid (MIPA), which can be converted into MIA by NosL. Biochemical assays with different MIPA isotopomers in D2 O and H2 O unambiguously indicated that the 5'-deoxyadenosyl (dAdo)-radical-mediated hydrogen abstraction is from the amino group of l-tryptophan and not a protein residue. Surprisingly, the dAdo-radical-mediated hydrogen abstraction occurs at two different sites of MIPA, thereby partitioning the substrate into different reaction pathways. Together with identification of an alpha,beta-unsaturated ketone shunt product, our study provides valuable mechanistic insight into NosL catalysis and highlights the remarkable catalytic flexibility of radical SAM enzymes. PMID- 26837060 TI - Systemic neutralization of TGF-beta attenuates osteoarthritis. AB - Osteoarthritis (OA) is a major source of pain and disability worldwide with no effective medical therapy due to poor understanding of its pathogenesis. Transforming growth factor beta (TGF-beta) has been reported to play a role in subchondral bone pathology and articular cartilage degeneration during the progression of OA. In this study, we demonstrated that systemic use of a TGF-beta neutralizing antibody (1D11) attenuates OA progression by targeting subchondral bone pathological features in rodent OA models. Systemic administration of 1D11 preserves the subchondral bone microarchitecture, preventing articular cartilage degeneration by inhibition of excessive TGF-beta activity, in both subchondral bone and the circulation. Moreover, the aberrant increases in the numbers of blood vessels, nestin(+) mesenchymal stromal/stem cells, and osterix(+) osteoblast progenitors were normalized by 1D11 systemic injection. Thus, systemic neutralization of excessive TGF-beta ligands effectively prevented OA progression in animal models, with promising clinical implications for OA treatment. PMID- 26837063 TI - Effectiveness of Mortuaries in Turkey: A Questionnaire Study. AB - AIM: The autopsy is an important step in solutions of forensic cases. The design and effectiveness of mortuaries are of great importance in terms of proper conduction of death examinations and autopsies. In addition, the safety of evidence, protection of public and staff health, and the quality of service offered to relatives of dead people are closely related to the effectiveness of mortuaries. The aim of this study was to determine whether mortuaries in Turkey meet international criteria. MATERIALS AND METHODS: Nineteen mortuaries were included in the study. The forensic medicine experts working in these mortuaries were given a questionnaire composed of questions about standards developed by the National Association of Medical Examiners (NAME) through the website my.questbase.com. RESULTS: Most of the mortuaries outside big cities (80%) did not have their own facilities. All of them could not control the chain of evidence and did not have a separate well-ventilated autopsy room where they could keep putrefied corpses. CONCLUSIONS: Most of the mortuaries did not meet most of the NAME criteria. The mortuaries, especially those in places other than big cities, had some deficiencies and mishandlings. Autopsy facilities and accessory laboratories should be enabled to meet NAME accreditation standards. PMID- 26837064 TI - Biodegradation of chlorpyrifos by bacterial genus Pseudomonas. AB - Chlorpyrifos is an organophosphorus pesticide commonly used in agriculture. It is noxious to a variety of organisms that include living soil biota along with beneficial arthropods, fish, birds, humans, animals, and plants. Exposure to chlorpyrifos may cause detrimental effects as delayed seedling emergence, fruit deformities, and abnormal cell division. Contamination of chlorpyrifos has been found about 24 km from the site of its application. There are many physico chemical and biological approaches to remove organophosphorus pesticides from the ecosystem, among them most promising is biodegradation. The 3,5,6-trichloro-2 pyridinol (TCP) and diethylthiophosphate (DETP) as primary products are made when chlorpyrifos is degraded by soil microorganisms which further break into nontoxic metabolites as CO(2), H(2)O, and NH(3). Pseudomonas is a diversified genus possessing a series of catabolic pathways and enzymes involved in pesticide degradation. Pseudomonas putida MAS-1 is reported to be more efficient in chlorpyrifos degradation by a rate of 90% in 24 h among Pseudomonas genus. The current review analyzed the comparative potential of bacterial species in Pseudomonas genus for degradation of chlorpyrifos thus, expressing an ecofriendly approach for the treatment of environmental contaminants like pesticides. PMID- 26837065 TI - Curing of plasmid pBMB28 from Bacillus thuringiensis YBT-020 using an unstable replication region. AB - Bacillus thuringiensis serovar finitimus strain YBT-020 is the well-studied spore crystal association (SCA) phenotypic strain, whose parasporal crystals adhere to spore after lysis of the mother cell. Its endogenous plasmids pBMB26 and pBMB28 were proved essential for this SCA phenotype. In our previous study, using conventional methods, pBMB26 cured derivative and both pBMB26 and pBMB28 cured derivative of YBT-020 were obtained. However, YBT-020 solely cured of pBMB28 could not be obtained. In this study, an unstable replication region of pBMB28 was identified and was used to construct an incompatible plasmid pRep28B. This incompatible plasmid was successfully used to cure plasmid pBMB28 and was easily eliminated through segregational instability under the optimum growth temperature of YBT-020. Therefore, an endogenous plasmid was cured from the B. thuringiensis strain utilizing plasmid incompatibility. Moreover, using an unstable replication region instead of a temperature sensitive (Ts) replication region is better to cure the incompatible plasmid because it can avoid culturing at higher temperature. This method provides an efficient method for plasmid curing in B. thuringiensis and other bacteria. PMID- 26837066 TI - Highly Flexible Graphene Oxide Nanosuspension Liquid-Based Microfluidic Tactile Sensor. AB - A novel graphene oxide (GO) nanosuspension liquid-based microfluidic tactile sensor is developed. It comprises a UV ozone-bonded Ecoflex-polydimethylsiloxane microfluidic assembly filled with GO nanosuspension, which serves as the working fluid of the tactile sensor. This device is highly flexible and able to withstand numerous modes of deformation as well as distinguish various user-applied mechanical forces it is subjected to, including pressing, stretching, and bending. This tactile sensor is also highly deformable and wearable, and capable of recognizing and differentiating distinct hand muscle-induced motions, such as finger flexing and fist clenching. Moreover, subtle differences in the handgrip strength derived from the first clenching gesture can be identified based on the electrical response of our device. This work highlights the potential application of the GO nanosuspension liquid-based flexible microfluidic tactile sensing platform as a wearable diagnostic and prognostic device for real-time health monitoring. Also importantly, this work can further facilitate the exploration and potential realization of a functional liquid-state device technology with superior mechanical flexibility and conformability. PMID- 26837067 TI - Protein Kinase R Degradation Is Essential for Rift Valley Fever Virus Infection and Is Regulated by SKP1-CUL1-F-box (SCF)FBXW11-NSs E3 Ligase. AB - Activated protein kinase R (PKR) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. Many viral proteins have adopted unique strategies to counteract the deleterious effects of PKR. The NSs (Non-structural s) protein which is encoded by Rift Valley fever virus (RVFV) promotes early PKR proteasomal degradation through a previously undefined mechanism. In this study, we demonstrate that NSs carries out this activity by assembling the SCF (SKP1-CUL1-F-box)(FBXW11) E3 ligase. NSs binds to the F-box protein, FBXW11, via the six amino acid sequence DDGFVE called the degron sequence and recruits PKR through an alternate binding site to the SCF(FBXW11) E3 ligase. We further show that disrupting the assembly of the SCF(FBXW11-NSs) E3 ligase with MLN4924 (a small molecule inhibitor of SCF E3 ligase activity) or NSs degron viral mutants or siRNA knockdown of FBXW11 can block PKR degradation. Surprisingly, under these conditions when PKR degradation was blocked, NSs was essential and sufficient to activate PKR causing potent inhibition of RVFV infection by suppressing viral protein synthesis. These antiviral effects were antagonized by the loss of PKR expression or with a NSs deleted mutant virus. Therefore, early PKR activation by disassembly of SCF(FBXW11-NSs) E3 ligase is sufficient to inhibit RVFV infection. Furthermore, FBXW11 and BTRC are the two homologues of the betaTrCP (Beta-transducin repeat containing protein) gene that were previously described to be functionally redundant. However, in RVFV infection, among the two homologues of betaTrCP, FBXW11 plays a dominant role in PKR degradation and is the limiting factor in the assembly of the SCF(FBXW11) complex. Thus, FBXW11 serves as a master regulator of RVFV infection by promoting PKR degradation. Overall these findings provide new insights into NSs regulation of PKR activity and offer potential opportunities for therapeutic intervention of RVFV infection. PMID- 26837068 TI - Guizhi Fuling Wan as a Novel Agent for Intravesical Treatment for Bladder Cancer in a Mouse Model. AB - Alternative intravesical agents are required to overcome the side effects currently associated with the treatment of bladder cancer. This study used an orthotopic bladder cancer mouse model to evaluate Guizhi Fuling Wan (GFW) as an intravesical agent. The effects of GFW were compared with those of mitomycin-C (Mito-C) and bacille Calmette-Guerin (BCG). We began by evaluating the response of the mouse bladder cancer cell line MB49 to GFW treatment, with regard to cell viability, cell cycle progression and apoptosis. MB49 cells were subsequently implanted into the urothelial walls of the bladder in female C57BL/6 mice. The success of the model was confirmed by the appearance of hematuria and tumor growth in the bladder. Intravesical chemotherapy was administered in accordance with a published protocol. In vitro data revealed that GFW arrested MB49 cell cycle in the G0/G1 phase, resulting in the suppression of cell proliferation and induced apoptosis. One possible mechanism underlying these effects is an increase in intracellular reactive oxygen species (ROS) levels leading to the activation of ataxia telangiectasia-mutated (ATM)/checkpoint kinase 2 (CHK2) and ATM/P53 pathways, thereby mediating cell cycle progression and apoptosis, respectively. This mouse model demonstrates the effectiveness of GFW in the tumor growth, with results comparable to those achieved by using BCG and Mito-C. Furthermore, GFW was shown to cause only mild hematuria. The low toxicity of the compound was confirmed by a complete lack of lesions on bladder tissue, even after 10 consecutive treatments using high concentrations of GFW. These results demonstrate the potential of GFW for the intravesical therapy of bladder cancer. PMID- 26837069 TI - Treatment with Anti-HMGB1 Monoclonal Antibody Does Not Affect Lupus Nephritis in MRL/lpr Mice. AB - High mobility group box 1 (HMGB1) is a nuclear DNA binding protein that acts as an alarmin when secreted. HMGB1 is increased in systemic lupus erythematosus and might represent a potential therapeutic target. We investigated whether treatment with an anti-HMGB1 antibody affects the development of lupus nephritis in MRL/lpr mice. Seven-week-old MRL/lpr mice were injected intraperitoneally twice weekly for 10 wks with 50 MUg monoclonal anti-HMGB1 (2G7, mouse IgG2b) (n = 12) or control antibody (n = 11). Control MRL/MPJ mice (n = 10) were left untreated. Every 2 wks, blood was drawn and urine was collected at wk 7, 11 and 17. Mice were sacrificed at 17 wks for complete disease evaluation. Plasma HMGB1 and anti HMGB1 levels were increased in MRL/lpr mice compared with control MRL/MPJ mice. There were no differences in albuminuria, urine HMGB1 and plasma levels of complement C3, anti-dsDNA and proinflammatory cytokines between untreated and treated mice at any time point. Lupus nephritis of mice treated with anti-HMGB1 monoclonal antibody (mAb) was classified as class III (n = 3) and class IV (n = 9), while mice treated with control mAb were classified as class II (n = 4), class III (n = 2) and class IV (n = 5). IgG and C3 deposits in kidneys were similar in mice treated with anti-HMGB1 mAb or control mAb. In conclusion, treatment with monoclonal anti-HMGB-1 antibody 2G7 does not affect development of lupus nephritis, disease progression or proinflammatory cytokine levels in MRL/lpr mice. This result indicates that blocking of HMGB1 by this neutralizing antibody does not affect lupus nephritis in MRL/lpr mice. PMID- 26837071 TI - Advancing Workforce Health at the Department of Homeland Security: Protecting Those Who Protect Us. PMID- 26837070 TI - Blood-brain Barrier Remodeling during Brain Metastasis Formation. AB - Our understanding of the process of metastatic progression has improved markedly over the past decades, yet metastasis remains the most enigmatic component of cancer pathogenesis. This lack of knowledge has serious health-related implications, since metastasis is responsible for 90% of all cancer-related mortalities. The brain is considered a sanctuary site for metastatic tumor growth, where the blood-brain barrier (BBB) and other components of the brain microenvironment, provide protection to the tumor cells from immune surveillance, chemotherapeutics and other potentially harmful substances. The interactions between tumor cells and the brain microenvironment, principally brain vascular endothelium, are the critical determinants in their progression toward metastasis, dormancy, or clearance. This review discusses current knowledge of the biology of metastatic progression, with a particular focus on the tumor cell migration and colonization in the brain. PMID- 26837073 TI - Global Health Engagement: Good to Great Over the Next 15 Years. PMID- 26837072 TI - Elderly Man With Epigastric Pain--Gallstone Ileus. PMID- 26837074 TI - The American Ambulance in Paris, 1914-1917 Part III: The American Ambulance Field Service. PMID- 26837075 TI - Respecting Other Cultures. PMID- 26837076 TI - A Glimmer of My Mother. PMID- 26837077 TI - Veterans' Preferences for Receiving Information About VA Services: Is Getting the Information You Want Related to Increased Health Care Utilization? AB - Although the current cohort of returning veterans has engaged more fully with care from the Department of Veterans Affairs (VA) than have veterans from previous eras, concern remains regarding low engagement with VA services, particularly for specialty services for diagnoses that can most negatively impact quality of life. This study used the framework of the Andersen Model to examine factors related to VA health care use in Operation Enduring Freedom/Operation Iraqi Freedom veterans. Match between veterans' preferences for source of information about VA programs and veterans' actual sources of information about VA services was examined as an additional predictor of help seeking. The study included 1,161 veterans recruited from the southeast United States. Results suggested that veterans prefer to receive information from VA publications and the web, whereas they actually receive information from VA publications and other veterans. Logistic regression suggested that the number of deployments, income, distance to VA, VA disability rating, self-rated health, and match between preferred source of information and actual source of information were significantly related to the use of VA services since deployment. These results suggest that future outreach efforts should focus on targeting veterans' health needs and preferences for care and source of information. PMID- 26837078 TI - Use of Near-Infrared Spectroscopy to Detect Sustained Hyperaemia Following Lower Extremity Trauma. AB - INTRODUCTION: Patients who sustain lower extremity trauma are at highest risk for acute compartment syndrome (ACS) during the first 48 hours after surgical stabilization. Near-infrared spectroscopy (NIRS) may be a useful monitoring tool for ACS during this period; however, expected normal values have yet to be established. This study sought to evaluate whether the expected hyperaemic response is present 48 hours postoperatively, using NIRS. MATERIALS AND METHODS: Participants consisted of 25 cases with acute unilateral lower extremity fractures. NIRS measurements for hemoglobin saturated with oxygen (rSO2) were taken approximately 48 hours after surgical stabilization for each compartment bilaterally, using the contralateral (uninjured) leg as an internal control. RESULTS: Mean rSO2 values taken 48 hours from surgical stabilization from each compartment of the patients' injured legs were significantly higher than the mean values of the contralateral legs (injured = 70, 68, 72, 70; contralateral = 55, 54, 57, 56 for anterior, lateral, deep posterior, and superficial posterior compartments, respectively; p < 0.0001 for all compartments). CONCLUSIONS: These results suggest that the hyperaemic response to injury remains present at 48 hours after surgical stabilization, and that NIRS values in an injured extremity should be expected to remain elevated throughout the window of concern for ACS. NIRS may be a valuable tool in monitoring leg injuries during this critical time period. PMID- 26837079 TI - "Tell Me What You Don't Remember": Care-Seeking Facilitators and Barriers in the Decade Following Repetitive Blast Exposure Among Army Combat Veterans. AB - OBJECTIVES: This study sought to understand facilitators and barriers to care seeking among blast-exposed veterans and service members who served before the implementation of systematic screening for traumatic brain injury. METHODS: Informed by principles of Grounded Theory, we used theoretical sampling and conducted 31 interviews with 15 veterans and 10 veteran family members. Data were iteratively collected and thematically analyzed. RESULTS: The most critical facilitator in initiating care was encouragement--verging on insistence--from a spouse, family member, or employer. Although respondents overwhelmingly described veteran and military health systems responding inadequately to patient needs, respondents also described exceptional health professionals who stood in contrast, dedicated to providing quality care. Barriers to ongoing care included: scheduling complications; redeployments; insufficient or inaccessible documentation of blast encounters or medical history; high provider turnover interrupting therapeutic progress; and poor patient-provider relationships. Respondents described providers as generally dismissive of or insensitive to many health needs. Respondents feared the system was incapable of helping them and described stigma against mental health care seeking in personal and professional spheres. CONCLUSIONS: Veterans and their families struggle to address multiple, confusing transformations after repetitive blast exposures. Complex, impersonal, and skeptical health system processes place an undue burden on care-seeking veterans and service members. PMID- 26837080 TI - Comparison of Select Health Outcomes by Deployment Health Assessment Completion. AB - The Department of Defense (DoD) requires service members to complete regular health assessments for identification of deployment-related physical/behavioral issues and environmental/occupational exposures. Compliance among active duty Department of the Navy personnel varies; however, and the impact of incomplete assessments on generalizability of results is unclear. This study examines the differences between Navy and Marine Corps service members who completed both the Post-Deployment Health Assessment and Post-Deployment Health Reassessment (n = 9,452) as compared to service members who never attempted either form (n = 5,603) in fiscal year 2010. Deployment rosters, assessments, and clinical data were analyzed to determine certified assessment completion rates and incidence of certain health conditions in these populations. Only 38.9% of applicable personnel met the completion and certification criteria for the required assessments. Service members who did not complete the forms were distinctly different demographically and at increased risk for psychotropic drug use, post traumatic stress disorder diagnosis, and traumatic brain injury diagnosis following deployment. The prevailing assumption that the risk of adverse health effects on operational forces can be estimated using the population that completed the required assessments is incorrect, and the true operational impact and medical burden of these conditions may be underestimated. PMID- 26837081 TI - Old Challenges and New Perspectives on Developing Military Physicians: The First 4 Years of the New Israeli Model. AB - Military medicine comprises a set of unique characteristics that differentiate it from other medical specialties. Faced with challenges in recruiting, educating, and training military physicians, the Israel Defense Forces Medical Corps redefined the paradigm for educating military physicians by establishing the Army Program for Excellence in medicine (APEX). This program created a military medical track at the Hebrew University-Hadassah School of Medicine in Jerusalem. All military track students attend a single medical school, which allows for a more focused and efficient program. The students study, dorm, and train together, forming a strong social network. They also receive significant financial, logistical, academic, and educational support. Finally, the program provides a full curriculum in military medical studies, composed of academic courses given for credits and an integrated training schedule designed to build and improve physical and mental fitness for the military environment. In this article, we provide an overview of APEX, including the admissions process and a descriptive analysis of the student body, and present our comprehensive approach to teaching academic military medicine. To the best of our knowledge, APEX represents one of the few fully integrated undergraduate longitudinal military medical education programs, allowing us to educate military physicians "from day one." PMID- 26837082 TI - Health Care Provider Burnout in a United States Military Medical Center During a Period of War. AB - OBJECTIVE: Provider burnout can impact efficiency, empathy, and medical errors. Our study examines burnout in a military medical center during a period of war. METHODS: A survey including the Maslach Burnout Inventory (MBI), deployment history, and work variables was distributed to health care providers. MBI subscale means were calculated and associations between variables were analyzed. RESULTS: Approximately 60% of 523 respondents were active duty and 34% had deployed. MBI subscale means were 19.99 emotional exhaustion, 4.84 depersonalization, and 40.56 personal accomplishment. Frustration over administrative support was associated with high emotional exhaustion and depersonalization; frustration over life/work balance was associated with high emotional exhaustion. CONCLUSIONS: Levels of burnout in our sample were similar to civilian medical centers. Sources of frustration were related to administrative support and life/work balance. Deployment had no effect on burnout levels. PMID- 26837083 TI - Assessment of Deployment-Related Exposures on Risk of Incident Mental Health Diagnoses Among Air Force Critical Care Providers: Nested Case-Control Study. AB - OBJECTIVES: The purpose of this study was to determine the association between deployment-related occupational/environmental exposures and incident postdeployment mental health (PDMH) conditions in a defined population of military health care professionals working in the deployed critical care environment. METHODS: A nested case-control study compared cohort members with a PDMH condition (cases, N = 146) with those without a PDMH condition (controls, N = 800) in terms of deployment-related exposures as ascertained using Postdeployment Health Assessment DD 2796 questionnaire data. Multivariable logistic regression models were used to compute odds ratios. RESULTS: Nonphysician career fields (i.e., nurses and medical technicians), exposure to dead bodies or people killed/wounded, history of a vehicular accident/crash, exposure to sand/dust, exposure to lasers, and use of mission-oriented protective posture (MOPP) overgarments were associated with increased likelihood for a PDMH condition. The infrequent exposures (i.e., vehicular accident/crash, lasers, and MOPP overgarments) were the exposures most strongly associated with subsequent PDHM conditions. CONCLUSIONS: For military health care providers returning from the deployed environment, several exposures are useful for predicting those at increased risk for a PDMH condition. However, there are likely many other important risk factors beyond those captured on the DD 2796 questionnaire. PMID- 26837084 TI - Family Relational Health, Psychological Resources, and Health Behaviors: A Dyadic Study of Military Couples. AB - In addition to facing stressors that are typical of life course development (e.g., marital struggles, balancing work/family demands), military families face additional stress attributed to their military context (e.g., deployments, relocations). Using a systems framework and stress process perspective, this study examined military couples' relational health, as a gauge for how couples collectively cope and address challenges as a united front and how their relational health influences crucial health behaviors (sleeping and eating) through the promotion or erosion of psychological resources (N = 236 couples). This study evaluated a latent variable structural equation dyadic model whereby each partner's perspective of their family's relational health was hypothesized to influence their own eating and sleeping behaviors (actor effects), as well as the eating and sleeping behaviors of their spouse (partner effects). The role of psychological resources (high self-efficacy, few depressive symptoms, and minimal anxiety) as a mechanism linking family functioning to health behaviors was also examined. Overall, the findings supported the hypothesized model, particularly for actor (intraindividual) effects. Discussion is provided pertinent to service providers and researchers, including the importance of improving, or maintaining, family relational health, as a means for encouraging positive health behaviors among active duty military members and their spouses. PMID- 26837085 TI - Does the Factor Structure of Military Sexual Stressors in Men Correspond to Women's? A Confirmatory Factor Analysis Using the Sexual Harassment Inventory. AB - OBJECTIVES: Unwanted sexual stressors experienced by military men and women are associated with a host of negative physical and mental health problems. Government officials are making it a priority to put a stop to these unwanted sexual experiences. However, the measure typically used measures sexual stressors much better for women than for men. The purpose of the present study was to test the factor structure of an alternative measure, the Sexual Harassment Inventory (SHI), to examine whether sexual stressors experienced by men correspond to women's experiences. METHODS: We used three preexisting datasets in which the SHI was used to assess active and former military members' sexual stressor experiences. We conducted an exploratory factor analysis to identify women's response patterns and a confirmatory factor analysis to determine whether men's response patterns corresponded to women's. RESULTS: Findings showed that the SHI has evidence of factorial validity in female service members and adequate, but not exceptional, factorial fit for male service members. CONCLUSIONS: It is imperative that more work be done to better understand how men experience and perceive potential military sexual stressors and how those perceptions and experiences compare to women's. PMID- 26837086 TI - Inter-Rater Reliability and Intra-Rater Reliability of Assessing the 2-Minute Push-Up Test. AB - The purpose of this study was to assess inter-rater reliability and intra-rater reliability of the 2-minute, 90 degrees push-up test as utilized in the Army Physical Fitness Test. Analysis of rater assessment reliability included both total score agreement and agreement across individual push-up repetitions. This study utilized 8 Raters who assessed 15 different videotaped push-up performances over 4 iterations separated by a minimum of 1 week. The 15 push-up participants were videotaped during the semiannual Army Physical Fitness Test. Each Rater randomly viewed the 15 push-up and verbally responded with a "yes" or "no" to each push-up repetition. The data generated were analyzed using the Pearson product-moment correlation as well as the kappa, modified kappa and the intra class correlation coefficient (3,1). An attribute agreement analysis was conducted to determine the percent of inter-rater and intra-rater agreement across individual push-ups.The results indicated that Raters varied a great deal in assessing push-ups. Over the 4 trials of 15 participants, the overall scores of the Raters varied between 3.0 and 35.7 push-ups. Post hoc comparisons found that there was significant increase in the grand mean of push-ups from trials 1-3 to trial 4 (p < 0.05). Also, there was a significant difference among raters over the 4 trials (p < 0.05). Pearson correlation coefficients for inter-rater and intra-rater reliability identified inter-rater reliability coefficients were between 0.10 and 0.97. Intra-rater coefficients were between 0.48 and 0.99. Intra rater agreement for individual push-up repetitions ranged from 41.8% to 84.8%. The results indicated that the raters failed to assess the same push-up repetition with the same score (below 70% agreement) as well as failed to agree when viewed between raters (29%). Interestingly, as previously mentioned, scores on trial 4 increased significantly which might have been caused by rater drift or that the Raters did not maintain the push-up standard over the trials. It does appear that the final push-up scores received by each participant was a close approximation of actual performance (within 65%) but when assessing physical performance for retention in the Army, a more reliable test might be considered. PMID- 26837087 TI - Effects of Age and Military Service on Strength and Physiological Characteristics of U.S. Army Soldiers. AB - Soldiers must maintain tactical performance capabilities over the course of their career. Loss in physical readiness may be a function of age and the operational demands associated with increasing years of service. The purpose of this study was to assess strength and physiological characteristics in different cohorts of U.S. Army Soldiers based on years of service and age. A total of 253 Soldiers (age: 28.1 +/- 6.8 years; height: 1.76 +/- 0.11 m; mass: 84.1 +/- 12.2 kg) participated. Individual subject cohorts were created based on years of service (1-5 years, 6-10 years, 11-15 years) and age (20-24 years, 25-29 years, 30-34 years, 35-39 years, 40-44 years). Testing included shoulder, knee, ankle, and torso strength, aerobic capacity/lactate threshold, anaerobic power/capacity, and body composition/total mass. Those with 11 to 15 years of service and between ages 30 and 34 had a higher percentage of body fat, and lower aerobic capacity and lactate threshold than younger Soldiers with fewer years of service. Physical training interventions should focus on maintenance of physiological characteristics to offset the loss of readiness at the similar time point of 11 to 15 years of service and 30 to 34 years of age. PMID- 26837088 TI - Democratizing Medicine. PMID- 26837089 TI - Case Reports: STAIR for Strengthening Social Support and Relationships Among Veterans With Military Sexual Trauma and PTSD. AB - Military sexual trauma (MST) is associated with high rates of post-traumatic stress disorder (PTSD) and multiple comorbid symptoms. In addition, women Veterans with MST report negative perceptions of social support, poor relationships, and difficulties in social and role functioning. Treatments for PTSD do not provide interventions to improve social or relationship functioning and do not consistently produce positive benefits regarding these outcomes. This article presents a series of case studies in which an intervention focused on building social support and relationship skills is delivered to Veterans with PTSD and MST. The intervention, Skills Training in Affective and Interpersonal Regulation (STAIR) promotes social engagement and skills that support greater role functioning. It can be used as a stand-alone treatment, as an adjunctive intervention to PTSD therapies or as part of a combination therapy in which skills precede trauma-focused work (STAIR Narrative Therapy). Further investigation is suggested to determine the added benefits of incorporating skills building to PTSD or other diagnosis-specific interventions. PMID- 26837090 TI - A Case of Undiagnosed Craniopharyngioma in an Army Mechanic. AB - Primary care providers are often the initial evaluators of soldiers presenting with acute eye complaints. It is crucial for these providers to master performing the basic eye examination with a systematic approach. Obtaining a thorough history is an important first step to the eye examination, but providers need to be careful not to narrow the diagnosis solely based on the history. Regardless of the presentation of the ocular complaints, a complete ocular examination must be performed. This article presents a case of brain tumor in an active duty soldier who was initially undiagnosed because of its unusual presentation. PMID- 26837091 TI - Discoid Medial Meniscus: A Case Report. AB - OBJECTIVES: Here we present a rare finding of a discoid medial meniscus. METHODS: Clinical reports, radiographs, magnetic resonance imaging (MRI) results, and intraoperative arthroscopic images highlight this rare clinical entity. RESULTS: We have demonstrated successful treatment with arthroscopic partial meniscectomy and saucerization of discoid medial meniscus. CONCLUSIONS: Discoid medial menisci are a rare cause of medial knee pain and should be considered if classic MRI findings are associated with mechanical symptoms. PMID- 26837092 TI - The world as it might (possibly) be. Correlation of wavelength and amplitude of visual peripheral stimuli with decompression sickness in 'teckies': a triple blinded, power-analysed study. PMID- 26837093 TI - Editorial on the special issue "harmful algal blooms (HABs) and public health: progress and current challenges". PMID- 26837095 TI - My Story. PMID- 26837094 TI - Introduction to the toxins special issue on plant toxins. PMID- 26837096 TI - Treatmnent Patterns for Pediatric Acute CHUs Media: A Gap in Evidence-Based Theory and Clinical Practice. AB - Unnecessary prescribing of antibiotics is costly, leads to serious unintended side effects, and increases the risk of developing antibiotic resistance. Children are at high risk of receiving unnecessary antibiotics because they consume more antibiotics than any other age group, likely due to inaccurate prescribing by health care providers. Treatment of acute otitis media is the most common reason children are prescribed antibiotics. Evidence-based guidelines regarding the appropriate treatment of nonsevere acute otitis media in children have been established. A retrospective, descriptive, chart review project was completed comparing the diagnosis and treatment of acute otitis media in children six months to 12 years of age in clinics and the emergency department of a large academic medical center with the American Academy of Pediatrics' treatment guidelines. Findings of the chart review included 100 patient encounters. Documentation indicated that although none of these children with acute otitis media met the guideline criteria for antibiotics, 92 of the 100 children were prescribed antibiotics. PMID- 26837097 TI - The Experience of Siblings of Children With Type 1 Diabetes. AB - Siblings of patients with diabetes mellitus have a unique experience that demands attention from health care providers. The purpose of this article is to explore the sibling experience, identify common fears, and provide the clinician with practical guidance on family-centered care for diabetes management. A comprehensive understanding of factors surrounding sibling adjustment is vital to ensure the best possible outcomes for children and families affected by diabetes. PMID- 26837098 TI - Impact of Hospital Admission Care At a Pediatric Unit: A Qualitative Study. AB - The time of admission to a hospital, especially when unplanned, has been reported as the most stressful moment of hospitalization for both parents and children (Odievre, 2001). This qualitative study explored parents and hospital staff's perceptions and experiences related to the process of admission to a pediatric unit. Focus groups, two with parents (total n = 12) and one with health care professionals (n = 6), were conducted, and content analysis inspired by Graneheim and Lundman (2004) was performed. Parents identified four categories of perceptions: 1) management of an uncertain situation at the time of admission, 2) feelings related to the child's illness, 3) parent perception of professional's performance, and 4) parent experience of their role. Health care professionals identified two categories: 1) hospital admission as a continuous care process, and 2) undertaking improvements in the admission process. A common theme emerged about the importance of parents' trust in professionals in order to build a therapeutic relationship. Findings underscore the need for strategies to improve the hospital pediatric admission process based on a parent-professional relationship of trust and confidence through continuous quality communication and support. These strategies would include providing a nurse in charge of the admission process to assure continuity of care throughout the child's hospitalization. PMID- 26837099 TI - Using Qualitative Descriptions To Improve Service. PMID- 26837100 TI - An Intervention to Improve the Comfort And Satisfaction of Nurses in the Telephone Triage of Child Maltreatment Calls. AB - Nurses are mandated reporters of actual or suspected child maltreatment or the threat thereof. The purpose of this quality improvement project was to determine the knowledge and comfort of nurses in telephone triage in pediatric clinics when dealing with suspected or actual child abuse calls. Nurses (N = 17) from three pediatric primary care clinics and one specialty care orthopedic clinic were surveyed. Based on results of the survey showing a lack of knowledge and adequate referral resources perceived by the nursing staff, resources and staff education were developed, along with a script for guiding maltreatment calls toward standardization of care. Following the intervention, nurses reported an increased comfort level when doing telephone triage for child maltreatment calls, an increase in knowledge of risk factors for county resources. Further, they reported a substantial shift in opinion about the need for a standardized script when responding to child maltreatment telephone calls. Nurses undertaking telephone triage of high-risk child maltreatment calls can improve their comfort and knowledge through a survey of their needs and directed education and resource development for the management of child maltreatment telephone triage. PMID- 26837101 TI - Rash, Rash, Go Away. PMID- 26837102 TI - Testicular Volume Discrepancy In an Adolescent Male. PMID- 26837103 TI - Bearing Bad News: Supporting Patients And Families through Difficult Conversations. PMID- 26837104 TI - Nursing Advocacy for patients and the Profession. PMID- 26837105 TI - Unequal Access: African Immigrants and American Health Care. PMID- 26837106 TI - Substance Abuse Among Nurses. PMID- 26837107 TI - A Two Way Street: How a Nursing School and Public School System Help Each Other. PMID- 26837108 TI - Nurse Fatigue: Dangerous for Nurses and Patients. PMID- 26837109 TI - [The end crowns the work (finis coronat opus)]. PMID- 26837110 TI - [Stab wounds of the hand and forearm due to Kuluna in Kinshasa (Democratic Republic of Congo): types of injuries and treatment]. AB - Democratic Republic of Congo (DRC), a particular form of juvenile delinquency and insecurity intensifies in the city of Kinshasa. This is the phenomenon Kuluna. It is organized gangs equipped with machetes and other weapons. The main objective of this study is to know the phenomenon Kuluna and describe the upper limb injuries caused by machetes, while insisting on the specifics of the management of these lesions in our communities. This retrospective descriptive study examines 14 cases of wounds of the hand and forearm due to stab phenomenon Kuluna, in Kinshasa. It covers the period from 1 November 2010 to 1 November 2013. Among the 14 patients with lesions in the hand and forearm admitted and treated at the Unit of Plastic Reconstructive and Aesthetic Surgery, Hand Surgery and Burns, University Clinics of Kinshasa to attacks due to the phenomenon Kuluna. We have 11 men and 3 women. The average age was 33, 5 years (extremes of 21 and 56 years). The right upper limb is reached that the left upper limb, respectively 12 patients and 2 patients. The lesions are localized to the wrist in the majority of cases (10 patients) in the palm of hand and in 3 patients in the fingers in 1 patient. The palmar surface is reached (10 cases) and the dorsal (4 cases). Zone 5 of the International Classification of flexor and Zone 8 topographic classification extensors at hand are the predilection sites of lesions respectively the palmar surface (6 out of 10) and the dorsal (2 case 4). The median nerve at the wrist is cut in half the cases. On bone lesions localized to the forearm, we observed a high incidence of fracture of the ulna (62.5%). The treatment begins with the stabilization of bone pieces, gestures revascularization and nerve sutures and suture tendon and finally skin coverage. Rehabilitation was mandatory, she supervises the actions of repair and it continues until the recovery of function. PMID- 26837111 TI - [Hyponatremia in the elderly: its role in frailty]. AB - Hyponatremia is the most common electrolyte disorder in elderly patients. The incidence is about 7% in elderly healthy people but can exceed 40% in hospitalized patients. Considering all its aetiologies hyponatremia is associated with increased mortality and appears as a factor of poor prognosis. Alteration in the regulation of water homeostasis in the elderly result from multiple consequence of aging: change in body composition, alteration in renal function and hormonal changes. The high frequency of nutritional problems, particularly protein malnutrition predisposes the elderly to the development of hyponatremia. Although diuretics especially thiazides are implicated as a frequent cause of hyponatremia on geriatric medicine, normovolemic hyponatremia and more particularly the syndrome of inappropriate antidiuresis is the most common cause. The aetiology of this syndrome can be determined in only approximately half of the cases. Cancers and medications, principally psychotropic agents commonly prescribed in geriatrics are the most frequent aetiologies. Hyponatremia could be a factor of frailty in geriatrics. Mild to moderate hyponatremia is generally considered asymptomatic but recent studies reported that asymptomatic hyponatremia contributes to neurological troubles like cognitive disorders, posture and gait impairments. Hyponatremia could be an independent risk factor of falls and could be associated with the development of osteoporosis. This review of the literature emphasizes the importance of screening and a systematic management of hyponatremia in the elderly people, even in the minor forms and those considered as asymptomatic. PMID- 26837112 TI - [Doping, sport and addiction--any links?]. AB - Sport is widely encouraged as it is beneficial for health. However, high performance sport is more and more associated to rather suspicious practices; doping is one of the best example. From a physician point of view, the use of doping agents is obviously a major concern because taking such products often induce serious adverse effects on health. The present manuscript aims to inform physicians about the most frequent doping practices. It also points out that intensive sport can generate an "addictive" behavior sharing with "common"addictions a loss of practice control, a lack of interest in other activities and even a sport's practice detrimental to athlete's health. Analysis of the doping issue needs to take this reality into account as some doping products display an established " addictive" effect. PMID- 26837113 TI - [Underwater dive in fresh water complicated by a cardiorespiratory arrest on obstructive shock]. AB - We present the case of a french patient who dived in fresh water in Lac de l'Eau d'Heure on 8 December 2014. The 35 meters deep diving was complicated by an obstructive shock resulting from lung overpressure and decompression illness. PMID- 26837114 TI - [Anti-aging medicine, a science-based, essential medicine]. AB - Anti-aging medicine is booming. It enters more and more in the programs of universities. Its hormone and nutritional tests and therapies rely on numerous scientific studies, including double-blind placebo-controlled randomized studies. Its methods are often innovative to obtain more information or benefits with greater safety. The fundamental purpose of anti-aging medicine is to optimize health and the quality of life, and through this, make the physical appearance more youthful. Well-chosen and well-dosed these treatments should not increase the risk of age-related diseases such as cancer and cardiovascular diseases, but on the contrary decrease it by the preventive aspect of the treatments. Opponents to anti-aging medicine fail in collecting valid scientific arguments. Their insistence on maintaining a society of elderly people looking and feeling as elderly people rather than actively participating in searching for ways to attenuate aging is harmful to all who follow them, to themselves in the first place. PMID- 26837115 TI - [Comment on the misappropriation of bibliographical references in science. The example of anti-aging medicine]. AB - This work constitutes a argued analysis of the publication of the article of Hertoghe et al. "Anti aging medicine, a science based, essential medicine " whose full and unreviewed publication was forced in the framework of the Belgian law on the right of reply to an earlier publication entitled " Anti-Aging Medicine: Science or Marketing? ". We confirm the absence of scientific evidence on the effectiveness of hormonal treatments used in this approach by highlighting the different techniques allowing doctors who promote this approach to make believe in their effectiveness. This is clearly to mix in one sentence established truths and unproven facts, use references inappropriately especially by misappropriation of studies on groups of patients with hormone deficiency in order to justify treatment in healthy subjects, to ignore recent references undermining ancient literature, to betray the authors' conclusions. Our critical analysis is also considering compliance with the guidelines for integrity in scientific publications. PMID- 26837116 TI - [The Anatomy, Biomechanical and Organogenesis Laboratory reinvests in the Warocque Institute at Parc Leopold]. PMID- 26837117 TI - [Carabin]. AB - The French word Carabin, meaning today a medicine student, has has various origins in course of time: a valueless person, a mute and assistant-surgeon, a carbine armed horseman and finaly a military medicine student but it is since the long stay in Strasbourg of those students that carabin became synonymous with medicine student. PMID- 26837118 TI - Critical thinking. PMID- 26837119 TI - Chapter Connections Day 2015. PMID- 26837120 TI - Compassion, Imagination, and Innovation: Dynamics 2015. PMID- 26837121 TI - Critical care nurses' decisions regarding physical restraints in two Canadian ICUs: A prospective observational study. AB - BACKGROUND: Legislation, guidelines and accreditation standards cal for the minimization of physical restraints, yet their use remains common in intensive care units (ICUs) both in Canada and internationally. In Canada, physical restraints are prescribed by physicians. However, assessment of their need, application, and removal are primarily the responsibility of ICU nurses. OBJECTIVES: We sought to describe Canadian ICU nurses' decision-making and practices of physical restraint application and discontinuation, as well as alternative measures attempted prior to their use for critically ill adults. METHODS: We conducted a prospective, observational study in two medical-surgical ICUs (tertiary academic and large community teaching hospital) of physical restraint use. RESULTS: We collected physical restraint data from the medical records of 141 patients from October 2011 to September 2012. Most restrained patients were mechanically ventilated (n = 118, 84%). Of the 247 reasons for restraint application identified for these 141 patients, agitation (n = 107, 43%), restlessness (n = 42, 17%) and use as a precautionary measure (n = 42, 17%) were the most commonly documented. Of the 167 behaviours observed and documented by nurses as indicative of agitation, pulling at the endotracheal tube or other lines/tubes (n = 111, 66%) was most commonly cited. Nurses documented the use of various strategies as an alternative to physical rest raint prior to their use for 46 (33%) patients. Of the 96 alternative strategies attempted, communication comprising reorientation and reminders was the most frequently documented (n = 26, 27%). Nurses reported having considered removing restraints during their shift for 61 (43%) patients. The criterion most commonly deemed essential for restraint removal was a calm patient (51 of the 104 reasons listed, 49%). CONCLUSIONS: Our study suggests that patient behaviour indicative of agitation was the most common reason for physical restraint application. Use as a precautionary measure and in situations where nurses' ability to be present at the bedside was reduced, as well as the limited use of alternative measures prior to physical restraint suggest restraint minimization may not be optimal. PMID- 26837122 TI - Safety implications of the dose change alert function in smart infusion pumps on the administration of high-alert medications. AB - BACKGROUND: Most intravenous medication errors occur during administration. Smart pumps can reduce the incidence of dose or rate errors using soft and hard limits. However, industry standard dose error reduction software misses errors that occur during titration. The dose change alert was developed to detect errors during titration. PURPOSE: To evaluate the safety implications of the dose change alert in the SIGMA Spectrum Infusion System on the administration of high-alert medications at The Ottawa Hospital. METHOD: This retrospective analysis included all titratable high-alert medication infusions administered between May 1 and October 31, 2014 (inclusive). Analysis of continuous quality improvement reports included drug library compliance, dose change alerts, soft limit confirmations and cancellations, and hard limit pull-back reports for each high-alert medication and care area. FINDINGS: Compliance with using the drug library was 96.8%. The percentage of dose change alert confirmations and cancellations within the soft limits were 48.1% and 1.9%, respectively. The titration of vasopressors resulted in the highest percentage (75%) of dose change alert confirmations. The titration of anticoagulants resulted in the highest percentage (12%) of dose change alert cancellations. Titration within the soft limits accounted for 65% of the alerts. CONCLUSIONS: This study provided insight into the safety implications of the dose change alert on the titration of high-alert medications. Key-press errors during titration of high-alert medications can cause patient harm, even within the soft limits. Nurses can be involved in customizing the percentage dose change limit for individual drugs within each care area to provide an additional safety check during titration. PMID- 26837123 TI - Ensuring the Price Is Right. PMID- 26837124 TI - Forward-Looking Strategies in the Wake of ICD-10. PMID- 26837125 TI - Patient-Friendly Billing Begins Before the Bill. PMID- 26837126 TI - ICD-10 Wins and Losses. PMID- 26837127 TI - ACCESS FOR ALL. New York City aims to improve care coordination for immigrants. PMID- 26837128 TI - MOST WIRED. Becoming partners with the patient and family in their care. PMID- 26837129 TI - DUAL BENEFITS. Hospitals take many paths to going green. PMID- 26837130 TI - PRACTICE GREEN. Saving costs and resources in the OR. PMID- 26837131 TI - GROWTH MANAGEMENT. Three questions with: Frank Sacco. PMID- 26837132 TI - TEAMWORK. Three competing Michigan health systems bring together three patients, three donors for 'historic' kidney swap. PMID- 26837133 TI - They call her 'the glue doctor'. PMID- 26837134 TI - Will Boeing Change Health Care? AB - Big employers like Boeing and Intel are directly contracting with hospitals in an effort to control health care prices. Some hospital CEOs see direct contracting as the future, while others wonder how they can participate. PMID- 26837135 TI - PEDIATRIC DESIGN: Child's Play (and a Whole Lot More). PMID- 26837136 TI - Low patient scores can hurt your reputation and your bottom line. So how can you get them up where they ought to be? AB - Low patient experience scores can hurt your reputation and your bottom line. So, how can you get them up to where they ought to be? PMID- 26837137 TI - Final thoughts. PMID- 26837138 TI - Child health research 'worryingly Low'. PMID- 26837139 TI - Neglect "the most common reason" for adults to contact the NSPCC. PMID- 26837140 TI - Support breastfeeding to reduce effects of poverty, says new report. PMID- 26837141 TI - 500k households could be out of poverty if they quit smoking. PMID- 26837142 TI - New mothers feel uncomfortable about breastfeeding in public. PMID- 26837143 TI - Consultation open on scope of whistleblower guardian role. PMID- 26837144 TI - Crucial developmental checks "may have been missed". PMID- 26837145 TI - Making an impression. PMID- 26837146 TI - A carer's journey. PMID- 26837147 TI - INVISIBLE BACKBONE. PMID- 26837148 TI - Supporting children and families through key transition stages. PMID- 26837149 TI - CPHVA Executive 2015 annual report. PMID- 26837150 TI - Female Genital Mutilation: A practical guide for health visitors and school nurses. PMID- 26837151 TI - Instant messaging: The way to improve access for young people to their school nurse. AB - Children and young people require ease of access to their school nurse. Alongside this, school nurses are charged with the need to work smarter, being cost effective and timely in response. School nursing teams across the country provide access through text messaging, however, there is presently no access provided to young people to have a consultation as a web-based chat facility. Using digital media, Doncaster school nurses have worked closely with young people to redesign and launch a totally interactive web- based clinic facility. This allows for improved access, reduction in travel costs and consultations to take place outside of the traditional times for accessing school nurses. This paper discusses a pilot project around the establishment of an e-clinic connecting young people and school nurses. It outlines the journey towards providing this innovative service in an attempt to provide cost-effective, timely services while reducing the barriers for service users. PMID- 26837152 TI - Improving health visitor emollient prescribing using a CQUIN-based approach. AB - Prescribing is an essential element of health visiting practice. This initiative used the payment framework of Commissioning for Quality and Innovation (CQUIN) to develop health visiting practice across a large health visiting workforce in the East Midlands. A focus on emollient prescribing practice was agreed and a guidance booklet regarding preferred emollient products was produced, based on the local formulary Each health visitor benefitted from receiving additional training and was given a guidance booklet to inform their practice. Targets were set for each quarter to demonstrate an improved prescribing adherence to the preferred product list.The targets were achieved for each quarter. Prescribing rates and confidence improved across the service. Therefore, it was demonstrated that specific guidance and ongoing support can improve prescribing practice within the health visiting service. PMID- 26837153 TI - Last word with...CPHVA PROFESSIONAL OFFICERS.... PMID- 26837154 TI - [In Process Citation]. PMID- 26837156 TI - [Differential diagnostic and therapeutic aspects of nasal obstruction]. AB - A nasal obstruction can have various causes. This publication describes various diseases of the nose and paranasal sinuses which cause nasal obstruction or which are associated with the symptom of nasal obstruction. The diagnosis and treatment of the diseases is discussed. Anatomical, physiological aspects and the general diagnosis of diseases of the nose and sinuses are also considered. PMID- 26837155 TI - [Pertussis (Whooping cough)--an update]. AB - Whooping cough is a highly contagious respiratory disease which is caused predominantly by the gram-negative bacterium Bordetella pertussis. Further Bordetella species such as B. parapertussis and the recently discovered species B. holmesii are also involved in whooping cough-like diseases. Depending on age, vaccination status and distance to pre-infection with B. pertussis, whooping cough shows a wide range of symptoms. The disease occurs at any age, leaving only short time immunity. During the last 15 years, in industrialized countries the number of reported pertussis cases has been increased markedly. The reason for this observation is still unclear Macrolides such as azithromycin and clarithromycin are regarded as antibiotics of first choice. In Germany, combination vaccines containing acellular pertussis vaccines is the most important strategy of prevention. To ensure the best possible protection against pertussis, booster doses at determined times should be given after primary vaccination in infancy. PMID- 26837157 TI - [Pharmacy based sore throat therapy according to current guidelines]. AB - Sore throat should be treated symptomatically in self-medication. Due to the mainly viral origin of the disease and the lack of efficiency data, local antibiotics or antiseptics should not be recommended. systemic analgesics as acetylsalicylic acid, acetaminophen, flurbiprofen, or ibuprofen are valid treatment options. Clinical trials suggest that ibuprofen shows the best benefit risk profile. Flurbiprofen could show efficiency in current trials but head-to head data with other analgesics (e.g. ibuprofen) are missing. There are currently three local anesthetics available with confirmed efficiency in clinical trials: lidocain (8mg), benzocaine (8 mg) and ambroxol (20 mg). They can be recommended in the first-line treatment. Among these ambroxol has the best documented benefit risk profile in the therapy of acute sore In the light of evidence based medicine, patients asking for local therapeutics can be treated with local anesthetics. PMID- 26837158 TI - [Infections with the MERS coronavirus--for the present no threat to Europe]. AB - In Saudi Arabia, a novel coronavirus named Middle East respiratory syndrome coronavirus (MERS-CoV) was isolated in 2012 from patients with severe respiratory symptoms. Up to now, more than 1600 MERS cases have been registered mainly in the Arabian Peninsula. MERS is usually accompanied with fever, cough, and shortness of breath. In many cases, pneumonia is observed. However, clinical features of MERS range from mild disease to acute respiratory distress syndrome and multiorgan failure resulting in death, especially in individuals with underlying comorbidities. To date, about one in three people died as a result of MERS. In Europe, MERS cases have only been registered in isolated travelers entering from the Middle East. PMID- 26837159 TI - [Vitamin D in oncology: Update 2015]. AB - Vitamin D deficiency is associated with increased incidence of breast and colon cancer as well as with an unfavourable course of non-Hodgkin lymphoma. Vitamin D deficiency is common in cancer patients and is associated with poor cancer prognosis and disease progression. In breast cancer patients under polychemotherapy with anthracycline and taxane, a significant drop in 25(OH)D levels was observed. Osteo-malacia represents a new and previously unreported risk factor for the development of bisphosphonate-related osteonecrosis of the jaw. In vitamin D deficiency (until it is corrected) oral and parenteral bisphosphonates should not be used. Vitamin D status should be monitored in all cancer patients and treated by adequate vitamin D3 supplementation. This applies in particular to cancer patients with poor nutritional status, treatment with aromatase inhibitors, bisphosphonates, and CTX containing anthracycline, taxane and monoclonal antibodies as well as in cases of muscular or mucocutaneous disorders, fatigue and tumor cachexia. PMID- 26837160 TI - [Multidrug-resistant bacteria require new treatment options]. AB - By now multidrug-resistant bacteria are a common cause of infections, especially in immunocompromised patient. These infections have to be treated with last resort antibiotics, such as colistin for the treatment of drug-resistant enterobacteriaceae or acinetobacter spp. Additionally the prevention of infections plays an important role in protecting critically ill patients. PMID- 26837161 TI - [In Process Citation]. PMID- 26837162 TI - [STUDIES ON THE CONSTITUENTS OF ARTEMISIA ANNUA L]. AB - Six crystalline components were isolated from the lipophilic fraction of Artemisia annua L. They have been identified as four sesquiterpenes, one flavonol and one coumarin. Qinghaosu I and III are new sesquiterpenes. Five main constituents, camphene, iso-artemisia ketone, 1-camphor, beta-carophyllene, and beta-pinene were identified from the volatile oil of this herb. PMID- 26837163 TI - [Progress on pharmacokinetic study of antibody-drug conjugates]. AB - Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs. PMID- 26837164 TI - [Advances of the anti-tumor research of metformin]. AB - Metformin is the most commonly prescibed drug for type 2 diabetes mellitus as it is inexpensive, safe, and efficient in ameliorating hyperglycemia and hyperinsulinemia. Numerous epidemiological studies indicate that diabetic population is not only at increased risk of cardiovascular complications, but also at substantially higher risk of many forms of malignancies. Meanwhile, epidemiological and clinical observation studies have shown that metformin use reduces risk of cancer in patients with type 2 diabetes mellitus and improves prognosis and survival rate of the cancer patients. Furthermore, metformin has been used for cancer therapy in clinical trials. Thus, metformin is emerging as a new cancer therapy or adjuvant anticancer drugs. This review summarizes recent progress in studies of metformin use and its molecular mechanism. PMID- 26837165 TI - [Current applications of dexamethasone for cancer treatment]. AB - Dexamethasone is a synthetic glucocorticoid that is widely used in clinical due to its multiple pharmacological effects. Recently, dexamethasone is increasingly utilized in anti-cancer therapy. It is frequently used to prevent side effects of chemotherapy such as nausea, vomiting and pain, as well as to increase the anti tumor activity of the cancer chemotherapeutic agents as a chemosensitizer and to inhibit tumor growth as an anti-cancer agent in some certain cancers. Dexamethasone produces the effects in anti-inflammation, anti-angiogenesis, control of estrogen activity and so on, by binding to glucocorticoid receptor to regulate gene expression of some important bio-signal molecules. Those signal pathways could interfere with the transcription of various factors which can regulate proliferation, invasion and metastasis of tumors. PMID- 26837166 TI - [Advances in the study of site-specific antibody-drug conjugates]. AB - Antibody drug conjugates (ADCs) are an emerging class of targeted therapeutics with the potential to improve therapeutic index over the traditional chemotherapy. However, it is difficult to control the site and stoichiometry of conjugation in mAb, typically resulting in heterogeneous mixtures of ADCs that are difficult to optimize. New methods for site-specific drug attachment allow development of more homogeneous conjugates and control of the site of drug attachment. In this article, the new literature on development of ADCs and site specific ADCs is reviewed. In addition, we summarized the various strategies in production of site-specific ADCs. PMID- 26837167 TI - [Mechanism and clinical progress of molecular targeted cancer therapy]. AB - Molecular target-based cancer therapy is playing a more and more important role in cancer therapy because of its high specificity, good tolerance and so on. There are different kinds of molecular targeted drugs such as monoclonal antibodies and small molecular kinase inhibitors, and more than 50 drugs have been approved since 1997. When the first monoclonal antibody, rituximab, was on the market. The development of molecular target-based cancer therapeutics has become the main approach. Based on this, we summarized the drugs approved by FDA and introduced their mechanism of actions and clinical applications. In order to incorporate most molecular targeted drugs and describe clearly various characteristics, we divided them into four categories: drugs related to EGFR, drugs related to antiangiogenesis, drugs related to specific antigen and other targeted drugs. The purpose of this review is to provide a current status of this field and discover the main problems in the molecular targeted therapy. PMID- 26837168 TI - [Effects of paclitaxel loaded-drug micelles on cell proliferation and apoptosis of human lung cancer A549 cells]. AB - This study was conducted to investigate the paclitaxel loaded by hydrazone bonds in poly(ethylene glycol)-poly(caprolactone) micelles (mPEG-PCL-PTX) on proliferation and apoptosis of human lung cancer A549 cells and its possible mechanisms of anti-tumor activity. The cell proliferation was measured with MTT assay. Flow cytometry were used to analyze the cell cycle. The cell apoptosis was analyzed using Hoechst/P staining. The expression levels of apoptotic genes expression in the mitochondrial apoptosis pathway were detected by RT-PCR and Western blotting, respectively. The mPEG-PCL-PTX could inhibit the proliferation of A549 cells and promote the apoptosis. The Bax, caspase-3 protein expression were increased while Bcl-2 protein expression was decreased in A549 cells. Results showed that the polymer containing hydrazone bond is non-toxic in vitro, the mPEG-PCL-PTX micelles can inhibit the proliferation and induce the apoptosis of A549 cells. Key words: paclitaxel; micelle; A549 cell; proliferation; cell cycle; apoptosis PMID- 26837169 TI - [Effects of triptolide on the expression of androgen receptor in human prostate LNCaP cells and its mechanism of action]. AB - To study the regulation of androgen receptor (AR) expression in human prostate cancer LNCaP cells by triptolide (TP) and the possible mechanism, by using qRT PCR and Western blot, the AR mRNA and protein levels in TP treated LNCaP cells were detected, and the AR protein level in TP and NF-kappaB inhibitor treated LNCaP cells was also detected; a series of pGL3-AR promoter reporter gene vectors were built using restriction-free cloning method, and the vectors were employed to investigate the effects of TP on the transcriptional activity of AR promoter in LNCaP cells; the upstream proteins which may play regulatory roles were detected using western blot assay. After treated LNCaP cells with TP for 48 h, AR mRNA and protein expressions decreased with increasing TP concentration. The expression of AR target gene PART1 and prostate specific antigen (PSA) was also downregulated by TP treatment; a series of pGL3-AR promoter reporter vectors were constructed and validated by sequencing and luciferase activity; the results of dual luciferase reporter assay showed that TP downregulated AR at the transcriptional level; PI3K/AKT/NF-kappaB pathway which is associated with AR promoter activity was drowregulated by TP. In conclusion, our results demonstrated that the transcriptional activity of AR in LNCAP cells was downregulated by TP, and PI3K/AKT/NF-kappaB pathway may be involved in the regulation mechanism. PMID- 26837170 TI - [Sensitization of human colon cancer HT-29 cells to TRAIL-induced apoptosis by gambognic acid]. AB - To investigate the effects of gambognic acid (GA) on TRAIL-induced apoptosis of cancer cells, human colon HT-29 cancer cells were treated with GA to promote apoptosis. Inhibition of the cell proliferation was measured with MTT assay and cell apoptosis was detected with formation of DNA ladders in agarose gel electrophoresis, and activation of caspase activity. The content of cytosolic reactive oxygen species (ROS) was measured with flow cytometry. The activities of Caspase-3, -8, -9 were detected using spectrophotometric assay. The levels of c FLIP, CHOP, DR4 and DR5 in cells were tested by Western blot. Combination of GA (1 ug . mL(-1)) and TRAIL (40 ng . mL(-1)) significantly reduced proliferation and increased apoptosis of HT-29 cells over those induced by each agent alone. Percentage of apoptotic cells was increased to 45.5%. GA markedly enhanced the intracellular ROS generation. Expression of CHOP, DR4 and DR5 was up-regulated to 7.38, 5.41, and 4.85 times of the control group, respectively. GA promoted activation of Caspase-3, -8, and -9 by TRAIL (P<0.05). Furthermore, the expression of anti-apoptotic protein c-FLIP was down-regulated to 0.22 +/- 0.08 times of the control group. In conclusion, GA sensitizes HT-29 cells to TRAIL induced apoptosis by promoting ROS-activated ERS pathways, up-regulating of DR4 and DR5, and inhibiting c-FLIP expression. PMID- 26837171 TI - [Synthesis and antitumor activity of fluoroquinolon-3-yl-s-triazole sulfide ketones and their derivatives from ciprofloxacin]. AB - To discover an efficient strategy for the conversion of the antibacterial activity of fluoroquinolones into the antitumor activity, the three series of C-3 s-triazole-based derivatives including sulfide ketones (6a-6g), thiosemicarbazones (7a-7g) and fused heterocyclic thiazolotriazoles (8a-8g) were synthesized from ciprofloxacin (1), respectively. The structures were characterized by elemental analysis and spectral data. The antitumor activity was tested against three tumor cell lines (Hep-3B, Capan-1 and HL60) using the MTT assay. The three types of compounds all exhibited stronger anti-proliferative activities than ciprofloxacin in the test. The order of their activities was in compounds 7>8>6, and the order of selectivity against cancer cell lines was Capan 1, Hep-3B and HL60. Meanwhile, the SAR revealed that some compounds with electron drawing group substituted such as fluoro- and nitro-phenyl compounds (6f, 7f, 8f) and (6g, 7g, 8g) displayed more significant activity than the control compounds, especially the IC50 values of thiosemicarbazone compounds 7f and 7g against Capan 1 was comparable to doxorubicin. Thus, a five-membered triazole as the C-3 bioisostere modified with the functionalized side-chain of sulfide-ketone thiosemicarbazone warrants special attention and further investigation. PMID- 26837172 TI - [Design, synthesis and antiproliferative activity in cancer cells of novel 18beta glycyrrhetinic acid derivatives]. AB - To investigate the anticancer effects of ring C in 18beta-glycyrrhetinic acid (GA), a series of GA derivatives featured with 9(11)-ene moiety in ring C were designed and synthesized. The structures were confirmed by IR, LC-MS and 1H NMR. Their inhibitory effects towards human prostate cancer PC-3 and leukemia HL-60 cell lines were determined. Most of the derivatives displayed stronger antiproliferative activities than GA. Particularly, compound 14 showed promising anticancer activity with the GI50 values of 4.48 umol . L(-1) and 1.2 umol . L( 1) against PC-3 and HL-60 cells respectively, which is worth further study. PMID- 26837173 TI - [In vitro targeting effect of lactoferrin modified PEGylated liposomes for hepatoma cells]. AB - A lactoferrin-containing PEGylated liposome system (Lf-PLS) was developed and tested in vitro as a hepatoma-targeting drug delivery system. PEGylated liposomes (PLS) were successfully prepared using the thin film hydration method with peglipid post insertion. Lf was covalently conjugated onto the carboxyl terminal of DSPE-PEG2000-COOH on liposomes. Coumarin-6 was used to trace Lf-PLS with fluorescence. The cellular uptake of this system was carried out in asialoglycoprotein receptor (ASGPR) positive HepG2 cells via confocal microscopy and flow cytometry. The Lf-PLS liposome was observed as spherical or oval vesicles with the particle size around 130 nm, zeta potential about -30 mV and encapsulation efficiency more than 80%. The confocal microscopy images and flow cytometry data demonstrated that Lf-PLS resulted in significantly higher cell association by ASGPR positive HepG2 cells compared to PLS. The association between Lf-PLS and cells were dependent on the concentration, time and temperature, which was inhibited by pre-incubation with excessive free Lf. The results suggest that Lf-PLS has a good targeting effect on HepG2 cells in vitro. The targeting mechanism may be related to the specific binding of Lf and ASGPR on HepG2 cells, which guides Lf-PLS to the cell surface to induce an active endocytosis process. All these results demonstrated that Lf-PLS might be a potential drug delivery system in targeting hepatocellular carcinoma, which deserves more research on its targeting ability, antitumor efficiency, and metabolism in vivo for treatment of hepatomacellular carcinoma. PMID- 26837174 TI - [Population pharmacokinetic/pharmacodynamic modeling of warfarin by nonlinear mixed effects model]. AB - The study aimed to establish a population pharmacokinetic/pharmacodynamic (PPK/PD) model of warfarin. PCR-RFLP technique was used to genotype the CYP2C9 and VKORC1 polymorphisms of 73 patients. RP-HPLC-UV method was used to determine the 190 plasma concentrations of warfarin. Application of NONMEM, the clinical information and 263 international normalized ratio (INR) monitoring data were used to investigate the effect of genetic, physiological, pathological factors, other medication on clearance and anticoagulant response. The final model of warfarin PPK/PD was described as follows: CL = thetaCL . (WT/60)thetaWT . thetaCYP . eetaCL (if CYP2C9*1/*1, thetaCYP = 1; if *1/*3, thetaCYP = 0.708); EC50 = thetaEC50 . thetaVKOR . eetaEC50 (if VKORC1- 1639AA, thetaVKOR = 1; if GA, thetaVKOR = 2.01; V = thetaV; K(E0) = thetaK(E0); Emax = thetaEmax; E0 = thetaE0 . eetaE0. Among them, the body weight (WT), CYP2C9 and VKORC1 genotype had conspicuous effect on warfarin PK/PD parameters. The goodness diagnosis, Bootstrap, NPDE verification showed that the final model was stable, effective and predictable. It may provide a reference for opitimizing the dose regimen of warfarin. PMID- 26837175 TI - [Pharmacokinetics and MR imaging of SPIO-shRNA dual functional molecular probe in vivo]. AB - In this study, we investigated the pharmacokinetics parameters of SPIO-shRNA dual functional molecular probe and observed the main organ distribution by MRI in vivo. Eighteen New Zealand white rabbits were randomly divided into three groups and injected intravenously with different doses of SPIO-shRNA molecular probe, respectively. The blood samples were collected to analyze the pharmacokinetic parameters by measuring the iron content at 30 minutes before and after the injection. Twenty-four Kun Ming (KM) mice were randomly divided into 4 groups: the control group was injected intravenously with physiological saline 200 uL per mouse via the tail vein, the other 3 groups were injected intravenously with different doses of SPIO-shRNA molecular probe. MRI observation was performed in 24 hours, and the liver, spleen, kidney, brain and muscle were collected for iron quantification with Prussian blue staining to determine distribution of the SPIO shRNA molecular probe in the main organ in vivo. Our results suggest that the molecular probe blood half-life is more than 3 hours. The data of MRI suggest the probe was distributed in liver and spleen, and the MRI signal was reduced with the increase in probe's doses (P < 0.05). The results of Prussian blue staining confirmed the results of MRI. Most of the probe could escape the phagocytosis of mononuclear phagocyte system. Our data provide the pharmacokinetic and distribution of SPIO-shRNA molecular probe in organs. Meanwhile, it suggests the choice of the time and dose of probe for MR imaging of tumor in vivo. PMID- 26837176 TI - [Simultaneous determination of clevidipine butyrate and its metabolite clevidipine acid in dog blood by liquid chromatography-tandem mass spectrometry]. AB - A rapid, sensitive and simple liquid chromatography-tandem mass spectrometry (LC MS/MS) method was developed and validated for the simultaneous determination of clevidipine butyrate and its primary metabolite clevidipine acid in dog blood. After one-step protein precipitation with methanol, the chromatographic separation was carried out on an Ecosil C18 column (150 mm x 4.6 mm, 5 um) with a gradient mobile phase consisting of methanol and 5 mmol . L(-1) ammonium formate. A chromatographic total run time of 13.0 min was achieved. The quantitation analysis was performed using multiple reaction monitoring (MRM) at the specific ion transitions of m/z 454.1 [M-H]- --> m/z 234.1 for clevidipine butyrate, m/z 354.0 [M-H]- --> m/z 208.0 for clevidipine acid and m/z 256.1 [M-H]- --> m/z 227.1 for elofesalamide (internal standard, IS) in the negative ion mode with electrospray ionization (ESI) source. The linear calibration curves for clevidipine butyrate and clevidipine acid were obtained in the concentration ranges of 0.5-100 ng . mL and 1-200 ng . mL(-1), separately. The lower limit of quantification of clevidipine butyrate and clevidipine acid were 0.5 ng . mL(-1) and 1 ng . mL(-1). The intra and inter-assay precisions were all below 12.9%, the accuracies were all in standard ranges. Stability testing indicated that clevidipine butyrate and clevidipine acid in dog blood with the addition of denaturant methanol was stable under various processing and/or handling conditions. The validated method has been successfully applied to a pharmacokinetic study of clevidipine butyrate injection to 8 healthy Beagle dogs following intravenous infusion at a flow rate of 5 mg . h(-1) for 0.5 h. PMID- 26837177 TI - [Synthesis and biological evaluation of novel pleuromutilin derivatives with nitrogen-containing heterocycles as antibacterial agents]. AB - A series of new pleuromutilins derivatives were designed and synthesized through coupling 2-aminothiazole ring of WL001 with different nitrogen-containing substituted heterocycles in the side chain. Their biological activities were evaluated against both Gram-positive and Gram-negative clinical bacteria in vitro Most new compounds displayed specificity to certain strain of bacteria. Particularly, compounds with saturated nitrogen-containing heterocycles exhibited significant antibacterial activities (0.062 5-8 ug . mL(-1)) superior or similar to those of amoxicillin, tiamulin and levofloxcin. Furthermore, treatment with 15a and 15b having piperidine or morpholine residues also could effectively inhibit Gram-negative bacteria. Therefore, our novel findings may provide a new insight into the design of novel pleuromutilin derivatives and lay the basis for further studies on the treatment of drug-resistance of pathogenic bacteria. PMID- 26837178 TI - [A new indole derivative from endophyte Myrothecium roridum IFB-E091 in Artemisia annua]. AB - Three compounds were isolated from solid culture of endophyte Myrothecium roridum IFB-E091 in Artemisia annua. Their structures were determined as (S)-(-)-N-[2-(3 hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-ethyl]-acetamide (1), N-(4 hydroxyphenethyl)acetamide (2) and asperfumoid (3), in which compound 1 was a new indole derivative. In cytotoxicity assay, the compound 1 had no obvious inhibition activity in human hepatoma cell line SMMC-7721 and human cervical carcinoma cell line HeLa. PMID- 26837179 TI - [Qualitative analysis of chemical constituents in Si-Wu Decoction based on TCM component database]. AB - In order to clarify the chemical constituents of Si-Wu Decoction rapidly and holistically, we analyzed the ethanol extract of Si-Wu Decoction by UPLC/Q-TOF MSE and UNIFI which based on traditional Chinese medicine database, the probable structures of 113 compounds were identified. The results show that this method can rapidly and effectively characterize the chemical compounds of Si-Wu Decoction and provide a new solution for identification of components from complex TCM extract. PMID- 26837180 TI - [Simultaneous determination of sivelestat and its metabolite XW-IMP-A in human plasma using HPLC-MS/MS]. AB - A simple and rapid method was developed based on high performance liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) to determine sivelestat and its metabolite XW-IMP-A in human plasma. After a simple protein precipitation, the samples and internal standards were analyzed on a C18 column by a gradient elution program. The mobile phase consisted of 30% acetonitrile in methanol and 5 mmol . L(-1) ammonium acetate at a flow rate of 0.7 mL . min(-1). The mass spectrometric data was collected in multiple reaction monitoring mode (MRM) in the negative electrospray ionization. The standard curves were linear in the range of 10.0-15,000 ng . mL(-1) for sivelestat, and 2.50-1000 ng . mL(-1) for XW-IMP-A. The low limits of quantitation were identified at 10.0 and 2.50 ng . mL for sivelestat and XW-IMP-A, respectively. The intra- and inter-day precision were within 11.3% and 13.1% for sivelestat and XW-IMP-A, and accuracy was 0.3% and 0.6% for sivelestat and XW-IMP-A, within the acceptable limits across all concentrations. The method was successfully validated in the pharmacokinetic study of sivelestat in healthy Chinese volunteers. PMID- 26837181 TI - [Fluorescence enhancement of flavoxate hydrochloride in alkali solution and its application in pharmaceutical analysis]. AB - Fluorescence enhancement reaction of flavoxate hydrochloride (FX) in strong alkali solution was studied, the mechanism of the reaction was investigated, and a novel fluorimetric method for analysis of FX in drug sample was established. FX has no intrinsic fluorescence, but it can slowly produce fluorescence in strong alkali solution. Heating can promote the fluorescence enhancement reaction. In 3D fluorescence spectra of the decomposition product of FX, two fluorescence peaks, located respectively at excitation wavelengths lambdaex/ emission wavelength lambdaem =223/410 nm, and 302/410 nm, were observed. Using quinine sulfate as a reference, fluorescence quantum yield of the decomposition product was measured to be 0.50. The structural characteriza- tion and spectral analysis of the decomposition product reveal that ester bond hydrolysis reaction of FX is firstly occurred during heating process, forming 3-methylflavone-8-carboxylic acid (MFA), then a cleavage reaction of the gamma-pyrone ring of MFA occurred, producing alpha, beta-unsaturated ketone. This product includes adjacent hydroxyl benzoic acid group in its molecule, which can form intramolecular hydrogen bond under alkaline condition, so that increase the conjugate degree and enhance the rigidity of the molecule, and thereby cause fluorescence enhancement. Based on this fluorescence enhancement reaction, a fluorimetric method was proposed for the determination of FX. A linear calibration curve covered the concentration range 0.020 3-0.487 ug . mL. The regression equation was I(F) = 23.9 + 5357.3 c, with correlation coefficient r = 0.999 7 (n = 8), detection limit D = 1.1 ng . mL(-1). The method was applied to the analysis of FX tablets, with a spiked recovery rate of 100.2%. The reliability of the method was verified by a UV spectrophotometric method. PMID- 26837182 TI - [An LC-MS/MS method for the simultaneous determination of amygdalin and paeoniflorin in human urine and application to urinary excretion study]. AB - ABSTRACT: The study aims to develop an LC-MS/MS method for the simultaneous determination of amygdalin and paeoniflorin in urine samples, and to investigate their urinary excretion characteristics in healthy volunteers after intravenous infusion administration of Huoxue-Tongluo lyophilized powder for injection (HTLPI). The urine samples were extracted by methanol, and then separated on a Hedera ODS-2 column with a mobile phase of acetonitrile and 5 mmol . L(-1) ammonium acetate buffer solution containing 0.05% formic acid (20:80). Electrospray ionization source was applied and operated in the positive ion mode using MRM. The method exhibited good linearity over the concentration range of 0.03 -40 ug . mL(-1). The values on both the occasions (intra- and inter-day) were all within 15% at three concentration levels. No matrix effect and carry over effect were observed. Amygdalin and paeoniflorin were stable in human urine under different storage conditions. Approximately 79.6% of the administered amount of amygdalin was excreted unchanged in urine within 24 h and which was 48.4% for paeoniflorin. The developed LC-MS/MS method can be applied to evaluate the urinary excretion of amygdalin and paeoniflorin. PMID- 26837183 TI - [The absorption and metabolism of oxymatrine in rat intestine]. AB - The purpose of this study is to systematically investigate the characteristics of absorption and metabolism of oxymatrine (OMT) using rat intestinal perfusion model. Ultra performance liquid chromatography (UPLC) and high performance liquid chromatography-electrospray ionization-quadrupole-time of flight mass spectrometry (HPLC-ESI(+)-Q-TOF-MS) were used to test absorption of OMT in intestine at 100, 200 and 400 umol . L(-1). The absorption rate and permeability of OMT is not dependent on concentration, but through passive absorption in intestine (P > 0.05). In the rat intestine, the absorbed amount of OMT was significantly different in four sections of the intestine in an order of duodenum > jejunum > ileum > colon (P < 0.05). OMT is metabolized into two metabolites in duodenum and jejunum, and matrine (MT) is the major one. PMID- 26837184 TI - [Determination of contact angle of pharmaceutical excipients and regulating effect of surfactants on their wettability]. AB - To study the effects of surfactants on wettability of excipients, the contact angles of six types of surfactants on the surface of two common excipients and mixture of three surfactants with excipients were measured using hypsometry method. The results demonstrated that contact angle of water on the surface of excipients was associated with hydrophilcity of excipients. Contact angle was lowered with increase in hydrophilic groups of excipient molecules. The sequence of contact angle from small to large was starch < sodium benzoate < polyvinylpyrrolidone < sodium carboxymethylcellulose < sodium alginate < chitosan < hydroxypropyl methyl cellulose 15 min was associated with death. Survivors had good long-term neurological outcome, demonstrating the value of timely CPR. PMID- 26837192 TI - Mechanisms of escape from the PGT128 family of anti-HIV broadly neutralizing antibodies. AB - BACKGROUND: Broadly neutralizing antibodies (bnAbs) directed against the mannose patch on the HIV envelope glycoprotein gp120 have several features that make them desirable targets for vaccine design. The PGT125-131 bnAb family is of particular interest due to its superior breadth and potency. The overlapping epitopes recognized by this family are intricate and neutralization requires interaction with at least two N-linked glycans (N332/N334, N295 or N301) in addition to backbone-mediated contact with the (323)IGDIR(327) motif of the V3 loop. We have recently shown that this bnAb family consists of two distinct antibody classes that can bind alternate arrangements of glycans in the mannose-patch in the absence of N332 thereby limiting viral escape. This led us to further investigate viral resistance and escape mechanisms to the PGT125-131 bnAb family. RESULTS: Using an escape virus isolated from the PGT125-131 donor as a guide, we show that mutating both the V3 core protein epitope and repositioning critical N-linked glycosylation sites are required to restore neutralization sensitivity. Interestingly, neutralization sensitivity could be restored via different routes for the two distinct bnAb classes within the PGT125-131 family, which may have been important in generating the divergence in recognition. We demonstrate that the observed V3 mutations confer neutralization resistance in other virus strains through both gain-of-function and escape studies. Furthermore, we show that the V3 loop is important in facilitating promiscuous binding to glycans within the mannose-patch. CONCLUSIONS: These data highlight the importance of the V3 loop in the design of immunogens aimed at inducing broad and potent bnAbs that can bind promiscuously to the mannose-patch. PMID- 26837194 TI - An unusual giant schwannoma of cervical sympathetic chain: a case report. AB - BACKGROUND: Schwannomas are benign, well-differentiated tumors that originate from Schwann cells. Involvement of the cervical sympathetic nerve is relatively rare. Computed tomography is indispensable for the diagnosis. The treatment is surgical. Histological examination confirms the diagnosis. Horner's syndrome postoperatively is supportive of the diagnosis. The rarity of giant cervical sympathetic chain schwannoma made the case of our patient interesting to report. Furthermore, our patient's immense tumor size is very rare, and we could not find any similar report in the literature. Cervical sympathetic chain schwannoma is frequently confused with schwannoma of the vagus nerve on clinical and radiological examination, and its diagnosis can therefore be challenging for clinicians, radiologists, and pathologists. CASE PRESENTATION: We report a rare case of cervical schwannoma in a 40-year-old Moroccan woman who presented with a large parapharyngeal mass. Computed tomography revealed a giant, heterogeneous, well-defined mass measuring 110 * 100 * 147 mm, occupying the right carotid triangle, and descending to the superior mediastinum. Surgical excision with a transcervical approach was done. Histological examination confirmed the diagnosis. The patient's postoperative course was marked by Horner's syndrome. CONCLUSIONS: Cervical sympathetic chain schwannoma is a rare, benign tumor. It should be considered in the differential diagnosis in patients presenting with a lateral neck mass. Surgical exploration must be discussed for a tumor with a large volume. PMID- 26837195 TI - A General Approach to the Diagnosis of Cutaneous Lymphomas and Pseudolymphomas. AB - Both pathology and dermatology rely heavily on a visual approach to learning, generating differential diagnoses, and making diagnoses. Pattern recognition and the development of diagnostic frameworks are essential elements in this process. In addition to images, several algorithms and summaries are presented in this article to provide a practical approach to the diagnosis of cutaneous lymphoproliferative disorders. The critical importance of clinical pathologic correlation is also emphasized. PMID- 26837193 TI - Behavioral and quality-of-life outcomes in different service models for methadone maintenance treatment in Vietnam. AB - BACKGROUND: Integrating HIV/AIDS and methadone maintenance treatment (MMT) services with existing health care delivery system is critical in sustaining efforts to fight HIV/AIDS in large injection-driven epidemics. However, efficiency of different integrative service models is unknown. This study assessed behavioral and health-related quality-of-life (HRQOL) outcomes of MMT in four service delivery models and explored factors associated with these outcomes of interest. METHODS: A cross-sectional survey was conducted in two HIV epicenters in Vietnam: Hanoi and Nam Dinh Province. All patients in five selected MMT clinics were invited to participate, and 1016 were interviewed (80-90% response rate). RESULTS: Respondents had a mean age of 35.8, taken MMT for average 16.5 months and 3.3% on MMT for 36-60 months. The MMT integrated with rural district health center (DHC) has the highest prevalence of concurrent drug use (11.3%). The percentage of condom use (last sexual intercourse) with primary and casual partners was lowest in the MMT at urban DHCs. Patients at the rural DHC reported very high proportions of pain/discomfort (37.8%), anxiety/depression (43.1%), and mobility (13.3%). In regression models, poorer HRQOL outcomes were found in MMT models in the rural areas or without general health care, and among those patients who were HIV positive, reported concurrent drug use, and had higher numbers of previous drug rehabilitation episodes. Mobility and anxiety/depression are factors that increased the likelihood of concurrent drug use among MMT patients. CONCLUSIONS: Outcomes of MMT were diverse across different integrative service models. Policies on rapid expansion of the MMT program in Vietnam should also emphasize on the integration with comprehensive health care services including psychological supports for patients. PMID- 26837196 TI - Mycosis Fungoides. AB - This article is a comprehensive review of mycosis fungoides (MF), the most common type of cutaneous T-cell lymphoma. The first portion of the article introduces epidemiologic features of MF. Next, the clinical presentation is described, followed by the microscopic features. This article addresses how to establish a diagnosis of MF and includes a discussion of the utility of ancillary testing, such as immunohistochemistry and T-cell clonality testing. The differential diagnosis is also discussed, with attention to how to distinguish MF from histopathologic mimics. The final section of the article discusses prognosis and risk of disease progression in MF. PMID- 26837197 TI - Mycosis Fungoides Variants. AB - Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that usually manifests as patches and plaques with a propensity for nonphotoexposed areas. MF is a common mimicker of inflammatory and infectious skin diseases, because it can be manifested with a wide variety of clinical and pathologic presentations. These atypical presentations of MF may be difficult to diagnose, requiring a high level of suspicion and careful clinicopathologic correlation. Within this array of clinical presentations, the World Health Organization classification recognizes 3 MF variants: folliculotropic MF, pagetoid reticulosis, and granulomatous slack skin. These 3 variants, as well as hypopigmented MF, are addressed in this article. PMID- 26837198 TI - Sezary Syndrome. AB - Sezary syndrome (SS), a type of cutaneous T-cell lymphoma with a poor prognosis, is characterized by erythroderma and leukemic involvement. Because of the rarity of SS and difficulty in diagnosis, data on this aggressive malignancy are scarce. In this review, the diagnosis and pathology of SS are summarized and an update is provided, highlighting microscopic features and novel molecular findings. The diagnostic challenge of SS is described, with an emphasis on the differential diagnosis of erythroderma and key points in distinguishing SS from other cutaneous T-cell malignancies. Finally, the prognosis is discussed, focusing on large, recent studies of SS patients. PMID- 26837199 TI - Cutaneous CD30-Positive Lymphoproliferative Disorders. AB - Cutaneous CD30+ lymphoproliferative disorders are the second most common types of cutaneous T-cell lymphomas. They represent a well-defined spectrum encompassing lymphomatoid papulosis (LyP), primary cutaneous anaplastic large-cell lymphoma (pcALCL), and borderline lesions. They share the expression of CD30 as a common phenotypic hallmark, but they differ in their clinical presentation, course, and histologic features. New variants have been recently identified, including CD8+ epidermotropic LyP type D, angioinvasive LyP type E, and ALK-positive pcALCL. This review describes clinical, histopathologic, and phenotypic variants; their differential diagnoses (benign and malignant); and the role of CD30 as a diagnostic, prognostic, and therapeutic marker. PMID- 26837200 TI - CD30-Negative Cutaneous T-Cell Lymphomas Other than Mycosis Fungoides. AB - Cutaneous T-cell lymphomas (CTCLs), other than mycosis fungoides/Sezary syndrome and the group of cutaneous CD30(+) lymphoproliferative disorders, are rare. These include subcutaneous panniculitis-like T-cell lymphoma (SPTCL); extranodal natural killer/T-cell lymphoma, nasal type; primary cutaneous peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS); and rare subtypes of PTCL, NOS. Apart from SPTCL and primary cutaneous CD4-positive small-medium pleomorphic T cell lymphoma, these lymphomas have in common aggressive clinical behavior and poor prognosis. Differentiation between these different types of CTCL may be difficult and requires integration of histopathologic findings with clinical data and the results of phenotypic and often molecular genetic studies. PMID- 26837201 TI - Primary Cutaneous B-Cell Lymphomas. AB - B-cell lymphomas occurring in the skin often tend to be of systemic origin with secondary cutaneous involvement. Primary cutaneous B-cell lymphomas tend to be indolent disorders, with the exception of primary cutaneous diffuse large B-cell lymphoma-leg type (PCDLBCL-LT). In indolent conditions, the distinction between cutaneous lymphoma and cutaneous lymphoid hyperplasia can be difficult. Integration of all available information, including the clinical setting, is crucial to arriving at the appropriate diagnosis. In this review, we cover the diagnostic approaches to primary cutaneous marginal zone lymphoma, primary cutaneous follicle center lymphoma, and PCDLBCL-LT, and discuss their differential diagnosis. PMID- 26837204 TI - Pathology of Cutaneous Lymphomas. PMID- 26837207 TI - Early lactate clearance for predicting active bleeding in critically ill patients with acute upper gastrointestinal bleeding: a retrospective study. AB - Not all patients with upper gastrointestinal bleeding (UGIB) require emergency endoscopy. Lactate clearance has been suggested as a parameter for predicting patient outcomes in various critical care settings. This study investigates whether lactate clearance can predict active bleeding in critically ill patients with UGIB. This single-center, retrospective, observational study included critically ill patients with UGIB who met all of the following criteria: admission to the emergency department (ED) from April 2011 to August 2014; had blood samples for lactate evaluation at least twice during the ED stay; and had emergency endoscopy within 6 h of ED presentation. The main outcome was active bleeding detected with emergency endoscopy. Classification and regression tree (CART) analyses were performed using variables associated with active bleeding to derive a prediction rule for active bleeding in critically ill UGIB patients. A total of 154 patients with UGIB were analyzed, and 31.2 % (48/154) had active bleeding. In the univariate analysis, lactate clearance was significantly lower in patients with active bleeding than in those without active bleeding (13 vs. 29 %, P < 0.001). Using the CART analysis, a prediction rule for active bleeding is derived, and includes three variables: lactate clearance; platelet count; and systolic blood pressure at ED presentation. The rule has 97.9 % (95 % CI 90.2 99.6 %) sensitivity with 32.1 % (28.6-32.9 %) specificity. Lactate clearance may be associated with active bleeding in critically ill patients with UGIB, and may be clinically useful as a component of a prediction rule for active bleeding. PMID- 26837208 TI - Interactions between dietary supplements in hospitalized patients. AB - Inpatient consumption of dietary and herbal supplements (DHS) has recently received research attention, particularly due to potential DHS-drug interactions. Nevertheless, DHS-DHS interactions have seldom been evaluated among hospitalized patients. We evaluated potential DHS-DHS interactions among inpatients. The study was a cross-sectional prospective study, conducted at Bnai Zion Medical Center (Haifa, Israel) in 2009-2014. A multi-disciplinary team of researchers constructed a questionnaire aimed at detecting DHS use among inpatients. The Natural Medicine Database was used to examine identified DHS for potential DHS DHS interactions. Then, medical files were reviewed to identify side effects potentially caused by such interactions and rate of documentation of DHS use. Univariate and multivariate logistic regression analyses were conducted to characterize potential risk factors for DHS-DHS interactions among hospitalized DHS users. Of 927 patients who agreed to answer the questionnaire, 458 (49.4 %) reported the use of 89 different DHS. Potential DHS-DHS interactions were identified in 12.9 % of DHS users. Three interactions were associated with the actual occurrence of adverse events. Patients at risk of DHS-DHS interactions included females (p = 0.026) and patients with greater numbers of concomitant medications (p < 0.0001) and of consumed DHS (p < 0.0001). In 88.9 % of DHS users, DHS use was not reported in medical files and only 18 % of the DHS involved in interactions were documented. Potential DHS-DHS interactions are common in inpatients, and may lead to hospitalization or worsen existing medical conditions. The causal relationship between potential interactions and actual adverse events requires further study. PMID- 26837209 TI - Dynamics of circulating microparticles in obesity after weight loss. AB - A definitive relationship between adiposity and MP production is yet to be demonstrated. The aim of our study was to prospectively evaluate the levels of microparticles (MP) in a group of 20 III degree obese patients before and after weight loss. Plasma levels of annexin V-MP, endothelial-derived MP, platelet derived MP (CD61+ and P-Selectin+), leukocyte-derived MP, tissue factor-bearing (TF+) and CD36+MP were prospectively measured in 20 patients with III degree obesity (BMI >= 40 kg/m(2)) before (T0) and 3 (T3) and 12 (T12) months after sleeve gastrectomy (SLG). Obese patients had lost 18 % of their body weight at T3 and 41 % at T12. We find that considering all MP, except for endothelial-derived MP, which had significantly decreased at T3, all MP subtypes had significantly decreased at T12. At T12, subjects showed a higher median level of all types of MP, except endothelial-derived MP, compared to T3, but without a statistically significant difference. The percentages of reduction of all the MP were significantly correlated with the percentage of reduction of BMI. The reductions of leukocyte-derived, TF+ and CD36+MP were significantly correlated with the reduction of leptin. Moreover, the reductions of leukocyte-derived and CD36+MP were significantly correlated with hs-CRP decrease. The decrease of BMI post-SLG in morbid obesity was matched with a decrease of circulating MP of endothelial, platelet, leukocyte origin, TF+ and CD36+. A trend of slight increase in all MP subtypes, except endothelial-derived, was detected 12 months after gastrectomy, indicating a possible underlying slow low-grade inflammatory/hypercoagulability state from adipose tissue before the potential overt weight gain. PMID- 26837210 TI - Low HIV testing uptake following diagnosis of a sexually transmitted infection in Spain: implications for the implementation of efficient strategies to reduce the undiagnosed HIV epidemic. AB - Sexually transmitted infections (STIs) are recognized as one of the conditions in which HIV testing is most clearly indicated. We analyse whether people diagnosed with an STI are being tested for HIV according to the experience of participants in an outreach rapid testing programme in Spain. Between 2008 and 2010, 6293 individuals underwent rapid testing and completed a self-administered questionnaire. We calculated the percentage of individuals that were diagnosed with an STI in the last 5 years and identified the setting where the last episode occurred. We then determined the percentage not receiving an HIV test after the last STI diagnosis and estimated the associated factors. Overall, 17.3% (N = 959) of participants reported an STI diagnosis in the last 5 years, of which 81.5% occurred in general medical settings. Sixty-one percent reported not undergoing HIV testing after their last STI diagnosis, 2.2% of whom reported they had refused the test. Not receiving an HIV test after the last STI diagnosis was independently associated with not being a man who has sex with men (MSM), having had fewer sexual partners, being diagnosed in general medical settings and having received a diagnosis other than syphilis. An unacceptably large percentage of people diagnosed with STI are not being tested for HIV because healthcare providers frequently fail to offer the test. Offering routine HIV testing at general medical settings, regardless of the type of STI diagnosed and population group, should be a high priority and is probably a more efficient strategy than universal screening in general healthcare settings. PMID- 26837213 TI - Deconvolution of ferredoxin, plastocyanin, and P700 transmittance changes in intact leaves with a new type of kinetic LED array spectrophotometer. AB - A newly developed compact measuring system for assessment of transmittance changes in the near-infrared spectral region is described; it allows deconvolution of redox changes due to ferredoxin (Fd), P700, and plastocyanin (PC) in intact leaves. In addition, it can also simultaneously measure chlorophyll fluorescence. The major opto-electronic components as well as the principles of data acquisition and signal deconvolution are outlined. Four original pulse-modulated dual-wavelength difference signals are measured (785-840 nm, 810-870 nm, 870-970 nm, and 795-970 nm). Deconvolution is based on specific spectral information presented graphically in the form of 'Differential Model Plots' (DMP) of Fd, P700, and PC that are derived empirically from selective changes of these three components under appropriately chosen physiological conditions. Whereas information on maximal changes of Fd is obtained upon illumination after dark-acclimation, maximal changes of P700 and PC can be readily induced by saturating light pulses in the presence of far-red light. Using the information of DMP and maximal changes, the new measuring system enables on-line deconvolution of Fd, P700, and PC. The performance of the new device is demonstrated by some examples of practical applications, including fast measurements of flash relaxation kinetics and of the Fd, P700, and PC changes paralleling the polyphasic fluorescence rise upon application of a 300-ms pulse of saturating light. PMID- 26837214 TI - Effectiveness of Mental Health First Aid training in Denmark: a randomized trial in waitlist design. AB - PURPOSE: To examine the effect of the Australian educational intervention Mental Health First Aid (MHFA) in a Danish context. Primary outcome was improvement concerning confidence in help-giving behavior towards people suffering from mental illness. Secondary outcomes were increased knowledge and ability to recognize mental illness and improved positive attitudes towards people suffering from mental health problems. METHOD: Study design was a randomized trial with a waitlist control group. The intervention group was compared with the control group at 6-month follow-up. Both groups completed at baseline and at 6-month follow-up. RESULTS: A significant difference was found between employees trained in the intervention group compared to the control group at 6-month follow-up on the items of confidence in making contact to (Cohen's d 0.17), talking to (Cohen's d 0.18) and providing help to (Cohen's d 0.31) people suffering from a mental health illness. Further, participants improved in knowledge (Cohen's d depression vignette 0.40/Cohen's d schizophrenia vignette 0.32) and in the ability to recognize schizophrenia OR = 1.75 (95 % CI 1.00-3.05), p = 0.05. A significant difference between the intervention group and control group at follow up concerning actual help offered was not found. Changes in attitudes were limited. CONCLUSION: The MHFA training was effective in a Danish context. PMID- 26837215 TI - Generation of Neural Progenitor Spheres from Human Pluripotent Stem Cells in a Suspension Bioreactor. AB - Conventional two-dimensional (2-D) culture systems cannot provide large numbers of human pluripotent stem cells (hPSCs) and their derivatives that are demanded for commercial and clinical applications in in vitro drug screening, disease modeling, and potentially cell therapy. The technologies that support three dimensional (3-D) suspension culture, such as a stirred bioreactor, are generally considered as promising approaches to produce the required cells. Recently, suspension bioreactors have also been used to generate mini-brain-like structure from hPSCs for disease modeling, showing the important role of bioreactor in stem cell culture. This chapter describes a detailed culture protocol for neural commitment of hPSCs into neural progenitor cell (NPC) spheres using a spinner bioreactor. The basic steps to prepare hPSCs for bioreactor inoculation are illustrated from cell thawing to cell propagation. The method for generating NPCs from hPSCs in the spinner bioreactor along with the static control is then described. The protocol in this study can be applied to the generation of NPCs from hPSCs for further neural subtype specification, 3-D neural tissue development, or potential preclinical studies or clinical applications in neurological diseases. PMID- 26837216 TI - Cell-penetrating peptide and antibiotic combination therapy: a potential alternative to combat drug resistance in methicillin-resistant Staphylococcus aureus. AB - The diverse pattern of resistance by methicillin-resistant Staphylococcus aureus (MRSA) is the major obstacle in the treatment of its infections. The key reason of resistance is the poor membrane permeability of drug molecules. Over the last decade, cell-penetrating peptides (CPPs) have emerged as efficient drug delivery vehicles and have been exploited to improve the intracellular delivery of numerous therapeutic molecules in preclinical studies. Therefore, to overcome the drug resistance, we have investigated for the first time the effects of two CPPs (P3 and P8) in combination with four antibiotics (viz. oxacillin, erythromycin, norfloxacin, and vancomycin) against MRSA strains. We found that both CPPs internalized into the MRSA efficiently at very low concentration (<10 MUM) which was non-toxic to bacteria as well as mammalian cells and showed no significant hemolytic activity. However, the combinations of CPPs (<=10 MUM) and antibiotics showed high toxicity against MRSA as compared to antibiotics alone. The significant finding is that P3 and P8 could lower the MICs against oxacillin, norfloxacin, and vancomycin to susceptible levels (generally <1 MUg/mL) for almost all five clinical isolates. Further, the bacterial cell death was confirmed by scanning electron microscopy as well as propidium iodide uptake assay. Simultaneously, time-kill kinetics revealed the increased uptake of antibiotics. In summary, CPPs assist to restore the effectiveness of antibiotics at much lower concentration, eliminate the antibiotic toxicity, and represent the CPP-antibiotic combination therapy as a potential novel weapon to combat MRSA infections. PMID- 26837218 TI - Adjustable under-expression of yeast mating pathway proteins in Saccharomyces cerevisiae using a programmed ribosomal frameshift. AB - Experimental research in molecular biology frequently relies on the promotion or suppression of gene expression, an important tool in the study of its functions. Although yeast is among the most studied model systems with the ease of maintenance and manipulation, current experimental methods are mostly limited to gene deletion, suppression or overexpression of genes. Therefore, the ability to reduce protein expressions and then observing the effects would promote a better understanding of the exact functions and their interactions. Reducing protein expression is mainly limited by the difficulties associated with controlling the reduction level, and in some cases, the initial endogenous abundance is too low. For the under-expression to be useful as an experimental tool, repeatability and stability of reduced expression is important. We found that cis-elements in programmed -1 ribosomal frameshifting (-1RFS) of beet western yellow virus (BWYV) could be utilized to reduced protein expression in Saccharomyces cerevisiae. The two main advantages of using -1RFS are adjustable reduction rates and ease of use. To demonstrate the utility of this under-expression system, examples of reduced protein abundance were shown using yeast mating pathway components. The abundance of MAP kinase Fus3 was reduced to approximately 28-75 % of the wild type value. Other MAP kinase mating pathway components, including Ste5, Ste11, and Ste7, were also under-expressed to verify that the -1RFS system works with different proteins. Furthermore, reduced Fus3 abundance altered the overall signal transduction outcome of the mating pathway, demonstrating the potential for further studies of signal transduction adjustment via under-expression. PMID- 26837217 TI - Characterization of a thermostable endo-1,3(4)-beta-glucanase from Caldicellulosiruptor sp. strain F32 and its application for yeast lysis. AB - beta-1,3-Glucans, important structural components of cell wall or nutritional components of the endosperm, are extensively found in bacteria, fungi, yeast, algae, and plants. The structural complexity of beta-1,3-glucans implies that the enzymatic depolymerization of polysaccharides needs combined activities of distinct enzymes. In this study, Lam16A-GH, the catalytic module of a putative glycoside hydrolase (GH) family 16 laminarinase/lichenase from thermophilic bacterium Caldicellulosiruptor sp. F32, was purified and characterized through heterologous expression in Escherichia coli. Lam16A-GH can hydrolyze both beta 1,3-glucan (laminarin) and beta-1,3-1,4-glucan (barley beta-glucan) revealed by analysis of the products of polysaccharide degradation using thin-layer chromatography (TLC). The time required for the loss of 50 % of its activity is 45 h under the optimal condition of 75 degrees C and pH 6.5. Oligosaccharides degradation assay indicated that Lam16A-GH can catalyze endo-hydrolysis of the beta-1,4 glycosidic linkage adjacent to a 3-O-substituted glucosyl residue in the mixed linked beta-glucans, as well as the beta-1,3 linkage. The survival rate of Saccharomyces cerevisiae cells depends on the addition of Lam16A-GH, and the cytoplasm protein was released from the apparently deconstructed yeast cells. These results indicate that the bi-functional thermostable Lam16A-GH exhibits unique enzymatic properties and potential for yeast lysis. PMID- 26837219 TI - The opposite roles of agdA and glaA on citric acid production in Aspergillus niger. AB - Citric acid is produced by an industrial-scale process of fermentation using Aspergillus niger as a microbial cell factory. However, citric acid production was hindered by the non-fermentable isomaltose and insufficient saccharification ability in A. niger when liquefied corn starch was used as a raw material. In this study, A. niger TNA 101DeltaagdA was constructed by deletion of the alpha glucosidase-encoding agdA gene in A. niger CGMCC 10142 genome using Agrobacterium tumefaciens-mediated transformation. The transformants A. niger OG 1, OG 17, and OG 31 then underwent overexpression of glucoamylase in A. niger TNA 101DeltaagdA. The results showed that the alpha-glucosidase activity of TNA 101DeltaagdA was decreased by 62.5 % compared with CGMCC 10142, and isomaltose was almost undetectable in the fermentation broth. The glucoamylase activity of the transformants OG 1 and OG 17 increased by 34.5 and 16.89 % compared with that of TNA 101DeltaagdA, respectively. In addition, for the recombinants TNA 101DeltaagdA, OG 1 and OG 17, there were no apparent defects in the growth development. Consequently, in comparison with CGMCC 10142, TNA 101DeltaagdA and OG 1 decreased the residual reducing sugar by 52.95 and 88.24 %, respectively, and correspondingly increased citric acid production at the end of fermentation by 8.68 and 16.87 %. Citric acid production was further improved by decreasing the non-fermentable residual sugar and increasing utilization rate of corn starch material in A. niger. Besides, the successive saccharification and citric acid fermentation processes were successfully integrated into one step. PMID- 26837220 TI - CEST theranostics: label-free MR imaging of anticancer drugs. AB - Image-guided drug delivery is of great clinical interest. Here, we explored a direct way, namely CEST theranostics, to detect diamagnetic anticancer drugs simply through their inherent Chemical Exchange Saturation Transfer (CEST) MRI signal, and demonstrated its application in image-guided drug delivery of nanoparticulate chemotherapeutics. We first screened 22 chemotherapeutic agents and characterized the CEST properties of representative agents and natural analogs in three major categories, i.e., pyrimidine analogs, purine analogs, and antifolates, with respect to chemical structures. Utilizing the inherent CEST MRI signal of gemcitabine, a widely used anticancer drug, the tumor uptake of the i.v.-injected, drug-loaded liposomes was successfully detected in CT26 mouse tumors. Such label-free CEST MRI theranostics provides a new imaging means, potentially with an immediate clinical impact, to monitor the drug delivery in cancer. PMID- 26837222 TI - Serial MRI evaluation following arthroscopic rotator cuff repair in double-row technique. AB - INTRODUCTION: So far, recurrent rotator cuff defects are described to occur in the early postoperative period after arthroscopic repair. The aim of this study was to evaluate the musculotendinous structure of the supraspinatus, as well as bone marrow edema or osteolysis after arthroscopic double-row repair. Therefore, magnetic resonance (MR) images were performed at defined intervals up to 2 years postoperatively. STUDY DESIGN: Case series; Level of evidence, 3. MATERIALS AND METHODS: MR imaging was performed within 7 days, 3, 6, 12, 26, 52 and 108 weeks after surgery. All patients were operated using an arthroscopic modified suture bridge technique. Tendon integrity, tendon retraction ["foot-print-coverage" (FPC)], muscular atrophy and fatty infiltration (signal intensity analysis) were measured at all time points. Furthermore, postoperative bone marrow edema and signs of osteolysis were assessed. RESULTS: MR images of 13 non-consecutive patients (6f/7m, ? age 61.05 +/- 7.7 years) could be evaluated at all time points until ? 108 weeks postoperatively. 5/6 patients with recurrent defect at final follow-up displayed a time of failure between 12 and 24 months after surgery. Predominant mode of failure was medial cuff failures in 4/6 cases. The initial FPC increased significantly up to 2 years follow-up (p = 0.004). Evaluations of muscular atrophy or fatty infiltration were not significant different comparing the results of all time points (p > 0.05). Postoperative bone marrow edema disappeared completely at 6 months after surgery, whereas signs of osteolysis appeared at 3 months follow-up and increased to final follow-up. CONCLUSIONS: Recurrent defects after arthroscopic reconstruction of supraspinatus tears in modified suture bridge technique seem to occur between 12 and 24 months after surgery. Serial MRI evaluation shows good muscle structure at all time points. Postoperative bone marrow edema disappears completely several months after surgery. Signs of osteolysis seem to appear caused by bio-absorbable anchor implantations. PMID- 26837221 TI - PRDX2 and PRDX4 are negative regulators of hypoxia-inducible factors under conditions of prolonged hypoxia. AB - Hypoxia-inducible factors (HIFs) control the transcription of genes that are crucial for the pathogenesis of cancer and other human diseases. The transcriptional activity of HIFs is rapidly increased upon exposure to hypoxia, but expression of some HIF target genes decreases during prolonged hypoxia. However, the underlying mechanism for feedback inhibition is not completely understood. Here, we report that peroxiredoxin 2 (PRDX2) and PRDX4 interact with HIF-1alpha and HIF-2alpha in vitro and in hypoxic HeLa cells. Prolonged hypoxia increases the nuclear translocation of PRDX2 and PRDX4. As a result, PRDX2 and PRDX4 impair HIF-1 and HIF-2 binding to the hypoxia response elements of a subset of HIF target genes, thereby inhibiting gene transcription in cells exposed to prolonged hypoxia. PRDX2 and PRDX4 have no effect on the recruitment of p300 and RNA polymerase II to HIF target genes and the enzymatic activity of PRDX2 and PRDX4 is not required for inhibition of HIF-1 and HIF-2. We also demonstrate that PRDX2 is a direct HIF target gene and that PRDX2 expression is induced by prolonged hypoxia. These findings uncover a novel feedback mechanism for inhibition of HIF transcriptional activity under conditions of prolonged hypoxia. PMID- 26837224 TI - Ordered expression pattern of Hox and ParaHox genes along the alimentary canal in the ascidian juvenile. AB - The Hox and ParaHox genes of bilateria share a similar expression pattern along the body axis and are known to be associated with anterior-posterior patterning. In vertebrates, the Hox genes are also expressed in presomitic mesoderm and gut endoderm and the ParaHox genes show a restricted expression pattern in the gut related derivatives. Regional expression patterns in the embryonic central nervous system of the basal chordates amphioxus and ascidian have been reported; however, little is known about their endodermal expression in the alimentary canal. We focus on the Hox and ParaHox genes in the ascidian Ciona intestinalis and investigate the gene expression patterns in the juvenile, which shows morphological regionality in the alimentary canal. Gene expression analyses by using whole-mount in situ hybridization reveal that all Hox genes have a regional expression pattern along the alimentary canal. Expression of Hox1 to Hox4 is restricted to the posterior region of pharyngeal derivatives. Hox5 to Hox13 show an ordered expression pattern correlated with each Hox gene number along the postpharyngeal digestive tract. This expression pattern along the anterior posterior axis has also been observed in Ciona ParaHox genes. Our observations suggest that ascidian Hox and ParaHox clusters are dispersed; however, the ordered expression patterns along the alimentary canal appear to be conserved among chordates. PMID- 26837223 TI - Salinity-induced inhibition of growth in the aquatic pteridophyte Azolla microphylla primarily involves inhibition of photosynthetic components and signaling molecules as revealed by proteome analysis. AB - Salinity stress causes adverse physiological and biochemical changes in the growth and productivity of a plant. Azolla, a symbiotic pteridophyte and potent candidate for biofertilizer due to its nitrogen fixation ability, shows reduced growth and nitrogen fixation during saline stress. To better understand regulatory components involved in salinity-induced physiological changes, in the present study, Azolla microphylla plants were exposed to NaCl (6.74 and 8.61 ds/m) and growth, photochemical reactions of photosynthesis, ion accumulation, and changes in cellular proteome were studied. Maximum dry weight was accumulated in control and untreated plant while a substantial decrease in dry weight was observed in the plants exposed to salinity. Exposure of the organism to different concentrations of salt in hydroponic conditions resulted in differential level of Na+ and K+ ion accumulation. Comparative analysis of salinity-induced proteome changes in A. microphylla revealed 58 salt responsive proteins which were differentially expressed during the salt exposure. Moreover, 42 % spots among differentially expressed proteins were involved in different signaling events. The identified proteins are involved in photosynthesis, energy metabolism, amino acid biosynthesis, protein synthesis, and defense. Downregulation of these key metabolic proteins appears to inhibit the growth of A. microphylla in response to salinity. Altogether, the study revealed that in Azolla, increased salinity primarily affected signaling and photosynthesis that in turn leads to reduced biomass. PMID- 26837226 TI - Control of interpenetration in a microporous metal-organic framework for significantly enhanced C2H2/CO2 separation at room temperature. AB - A novel non-interpenetrated three-dimensional porous metal-organic framework UTSA 68 has been controllably synthesized by altering the reaction conditions. The resulting UTSA-68a shows a notably higher porosity and adsorption selectivity (3.5-5) for C2H2/CO2 separation compared to that of doubly interpenetrated ZJU 30a (1.7-2.4) at room temperature. PMID- 26837225 TI - Changes in keratins and alpha-smooth muscle actin during three-dimensional reconstitution of eccrine sweat glands. AB - We have examined the changes of keratins and alpha-SMA at various time points in order to investigate the development and differentiation of eccrine sweat gland cells during the course of three-dimensional (3D) reconstitution. Mixtures of eccrine sweat gland cells and Matrigel were injected subcutaneously into the inguinal regions of nude mice. At 1, 2, 4, 6, 8, 14, 21, 28, 35, and 42 days post implantation, Matrigel plugs were removed and immunostained. We found that during 3D reconstitution, keratin and alpha-SMA expression changed in a time-dependent manner. At day 1, all cells stained positively for keratin isoforms K5, K14, and K15, with the staining intensity of K15 being weak and K5 and K14 being strong, but none of the cells displayed K7, K8, or alpha-SMA. As time progressed, spheroid-like structures formed with the inner layer acquiring K7 and K8, but losing K5 and K14 expression, and the outer layer acquiring alpha-SMA expression, but losing K15 expression. K8 expression was first noted at day 14, and K7 and alpha-SMA at day 21. The loss of K15 expression was first noted at day 14, K14 at day 21, and K5 at day 28. At 28, 35, and 42 days, the spheroid-like structures could be distinguished, by immunohistochemistry, as having secretory coil-like and coiled duct-like structures. We conclude that the changes in expression of keratins and alpha-SMA in 3D-reconstituted eccrine sweat glands are similar to those of native eccrine sweat glands, indicating that the 3D reconstitution of sweat glands provides an excellent model for studying the development, cytodifferentiation, and regulation of eccrine sweat glands. PMID- 26837227 TI - Does one score fit all? Measuring risk in ulcerative colitis. AB - BACKGROUND: The American College of Surgeons Surgical Risk Calculator was developed to improve risk stratification and surgical quality but has not been studied at the institutional level for specific disease states, like ulcerative colitis (UC). METHODS: UC patients undergoing colorectal resection had predicted risk calculator data compared with actual outcomes for length of stay (LOS), complications, reoperation, and death. Main outcome measures were the difference in actual vs predicted outcomes. RESULTS: Seventy patients were evaluated. The actual and predicted mean LOS was identical, but not representative of the actual LOS picture, which had 10 LOS outliers (14.3%). The actual incidence of any complication (P < .001) and major complications (P < .001) was higher than predicted. The most common complications actually encountered-intrabdominal abscess (14.3%), postoperative ileus (7.2%), and anastomotic leak (5.7%), were not even calculated by the tool. CONCLUSIONS: For UC, the calculator poorly evaluates relevant risks, complications, and is greatly impacted by outliers. These limitations caution use for surgical quality reporting and determining specific patient outcomes, at least in UC. PMID- 26837228 TI - Clinical Outcomes in a Large Cohort of Musculoskeletal Patients Undergoing Chiropractic Care in the United Kingdom: A Comparison of Self- and National Health Service-Referred Routes. AB - OBJECTIVE: An innovative commissioning pathway has recently been introduced in the United Kingdom allowing chiropractic organizations to provide state-funded chiropractic care to patients through referral from National Health Service (NHS) primary care physicians. The purpose of this study was to examine the outcomes of NHS and private patient groups presenting with musculoskeletal conditions to chiropractors under the Any Qualified Provider scheme and compare the clinical outcomes of these patients with those presenting privately. METHODS: A prospective cohort design monitoring patient outcomes comparing self-referring and NHS-referred patients undergoing chiropractic care was used. The primary outcome was the change in Bournemouth Questionnaire scores. Within- and between group analyses were performed to explore differences between outcomes with additional analysis of subgroups as categorized by the STarT back tool. RESULTS: A total of 8222 patients filled in baseline questionnaires. Of these, NHS patients (41%) had more adverse health measures at baseline and went on to receive more treatment. Using percent change in Bournemouth Questionnaire scores categorized at minimal clinical change cutoffs and adjusting for baseline differences, patients with low back and neck pain presenting privately are more likely to report improvement within 2 weeks and to have slightly better outcomes at 90 days. However, these patients were more likely to be attending consultations beyond 30 days. CONCLUSIONS: This study supports the contention that chiropractic services as provided in United Kingdom are appropriate for both private and NHS-referred patient groups and should be considered when general medical physicians make decisions concerning referral routes and pain pathways for patients with musculoskeletal conditions. PMID- 26837229 TI - Attenuation Effect of Spinal Manipulation on Neuropathic and Postoperative Pain Through Activating Endogenous Anti-Inflammatory Cytokine Interleukin 10 in Rat Spinal Cord. AB - OBJECTIVES: The purpose of this study was to investigate roles of the anti inflammatory cytokine interleukin (IL) 10 and the proinflammatory cytokines IL 1beta and tumor necrosis factor alpha (TNF-alpha) in spinal manipulation-induced analgesic effects of neuropathic and postoperative pain. METHODS: Neuropathic and postoperative pain were mimicked by chronic compression of dorsal root ganglion (DRG) (CCD) and decompression (de-CCD) in adult, male, Sprague-Dawley rats. Behavioral pain after CCD and de-CCD was determined by the increased thermal and mechanical hypersensitivity of the affected hindpaw. Hematoxylin and eosin staining, whole-cell patch clamp electrophysiological recordings, immunohistochemistry, and enzyme-linked immunosorbent assay were used to examine the neural inflammation, neural excitability, and expression of c-Fos and PKC as well as levels of IL-1beta, TNF-alpha, and IL-10 in blood plasma, DRG, or the spinal cord. We used the activator adjusting instrument, a chiropractic spinal manipulative therapy tool, to deliver force to the spinous processes of L5 and L6. RESULTS: After CCD and de-CCD treatments, the animals exhibited behavioral and neurochemical signs of neuropathic pain manifested as mechanical allodynia and thermal hyperalgesia, DRG inflammation, DRG neuron hyperexcitability, induction of c-Fos, and the increased expression of PKCgamma in the spinal cord as well as increased level of IL-1beta and TNF-alpha in DRG and the spinal cord. Repetitive Activator-assisted spinal manipulative therapy significantly reduced simulated neuropathic and postoperative pain, inhibited or reversed the neurochemical alterations, and increased the anti-inflammatory IL-10 in the spinal cord. CONCLUSION: These findings show that spinal manipulation may activate the endogenous anti-inflammatory cytokine IL-10 in the spinal cord and thus has the potential to alleviate neuropathic and postoperative pain. PMID- 26837230 TI - An Electronic Patient-Reported Outcome Measures System in UK Chiropractic Practices: A Feasibility Study of Routine Collection of Outcomes and Costs. AB - OBJECTIVE: The purpose of this study was to test the feasibility of collecting valid and widely used health outcomes, including information concerning cost of care, using a Web-based patient-driven patient-reported outcome measure (PROM) collection process within a cohort of UK chiropractic practices. METHODS: A Web based PROM system (Care Response) was used. Patients with low back and neck pain were recruited from a group of chiropractic practices located in the United Kingdom. Information collected included demographic data, generic and condition specific PROMs at the initial consultation and 90 days later, patient-reported experience measures, and additional health seeking to estimate costs of care. RESULTS: A group of 33 clinics provided information from a total of 1895 patients who completed baseline questionnaires with 844 (45%) completing the measures at 90-day follow-up. Subsequent outcomes suggest that more than 70% of patients improved over the course of treatment regardless of the outcome used. Using the baseline as a virtual counterfactual with respect to follow-up, we calculated quality-adjusted life years and the cost thereof resulting in a mean quality adjusted life years gained of 0.8 with an average cost of L895 per quality adjusted life year. CONCLUSION: Routine collection of PROMs, including information about cost, is feasible and can be achieved using an online system within a clinical practice environment. We describe a Web-based collection system and discuss the choice of measures leading to a comprehensive understanding of outcomes and costs in routine practice. PMID- 26837231 TI - Influence of Subclinical Neck Pain on the Ability to Perform a Mental Rotation Task: A 4-Week Longitudinal Study With a Healthy Control Group Comparison. AB - OBJECTIVE: Mental rotation of objects and the frame of reference of those objects are critical for executing correct and skillful movements and are important for object recognition, spatial navigation, and movement planning. The purpose of this longitudinal study was to compare the mental rotation ability of those with subclinical neck pain (SCNP) to healthy controls at baseline and after 4 weeks. METHODS: Twenty-six volunteers (13 SCNP and 12 healthy controls) were recruited from a university student population. Subclinical neck pain participants had scores of mild to moderate on the Chronic Pain Grade Scale, and controls had minimal or no pain. For the mental rotation task, participants were presented with an object (letter "R") on a computer screen presented randomly in either normal or backwards parity at various orientations (0 degrees , 45 degrees , 90 degrees , 135 degrees , 180 degrees , 225 degrees , 270 degrees , and 315 degrees ). Participants indicated the object's parity by pressing "N" for normal or "B" for backwards. Each orientation for normal and backward parities was presented 5 times, and the average response time for all letter presentations was calculated for each participant, at baseline and 4 weeks later. RESULTS: Both groups had overall improved response times from baseline to 4 weeks. Healthy participants had significantly improved response times compared to SCNP, both at baseline (P < .05) and 4 weeks (P < .05). CONCLUSIONS: Healthy participants performed better than the SCNP group at both time points. Subclinical neck pain may impair the ability to perform a complex mental rotation task involving cerebellar connections, possibly due to altered body schema. PMID- 26837232 TI - Five minutes with . . . Chaand Nagpaul. PMID- 26837233 TI - Percutaneous endoscopic gastrostomy versus percutaneous radiological gastrostomy for swallowing disturbances. AB - BACKGROUND: Gastrostomy has been established as the standard procedure for administering long-term enteral nutrition in individuals with swallowing disturbances. Percutaneous gastrostomy is a less-invasive approach than open surgical gastrostomy, and can be accomplished via endoscopy (percutaneous endoscopic gastrostomy or PEG) or sonographic or fluoroscopic guidance (percutaneous radiological gastrostomy or PRG). Both techniques have different limitations, advantages, and contraindications. In order to determine the optimal technique for long-term nutritional supplementation many studies have been conducted to compare the outcomes of these two techniques; however, it remains unclear as to which method is superior to the other with respect to both efficacy and safety. OBJECTIVES: To compare the safety and efficacy of PEG and PRG in the treatment of individuals with swallowing disturbances. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, January 2016); MEDLINE (1946 to 22 January 2016); EMBASE (1980 to 22 January 2016); the reference lists of identified articles; databases of ongoing trials, including the Chinese Cochrane Centre Controlled Trials Register; and PubMed. We applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing PEG with PRG in individuals with swallowing disturbances, regardless of the underlying disease. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated the search results and assessed the quality of the studies. Data analyses could not be performed as no RCTs were identified for inclusion in this review. MAIN RESULTS: We identified no RCTs comparing PEG and PRG for percutaneous gastrostomy in individuals with swallowing disturbances. The large body of evidence in this field comes from retrospective and non randomised controlled studies and case series. Based on this evidence, both PEG and PRG can be safely performed in selected individuals, although both are associated with major and minor complications. A definitive RCT has yet to be conducted to identify the preferred percutaneous gastrostomy technique. AUTHORS' CONCLUSIONS: Both PEG and PRG are effective for long-term enteral nutritional support in selected individuals, though current evidence is insufficient to recommend one technique over the other. Choice of technique should be based on indications and contraindications, operator experience and the facilities available. Large-scale RCTs are required to compare the two techniques and to determine the optimal approach for percutaneous gastrostomy. PMID- 26837234 TI - President's Page. PMID- 26837235 TI - Incremental prognostic value of quantitative plaque assessment in coronary CT angiography during 5 years of follow up. AB - OBJECTIVE: We sought to assess the incremental prognostic value of quantitative plaque characterization beyond established CT risk scores. BACKGROUND: Several plaque characteristics detectable by coronary computed tomographic angiography (coronary CTA) are thought to be indicative of vulnerable plaques and subsequent cardiac events, particularly low attenuation plaque volume (LAPV), positive remodeling and the napkin-ring sign which is high density vascular adhesion with a small center of low density. It is unknown how quantitative plaque assessment can contribute to the long-term prediction of cardiovascular events in relation to established CT risk scores such as the calcium score or Segment Stenosis Score (SSS). METHODS: In 1168 consecutive patients with suspected coronary artery disease (CAD), calcium score measurement and coronary plaque characterization was performed comprising the presence of calcified, non-calcified, and partially calcified plaques on a per-segment basis. In all non-calcified or partially calcified plaques, semi-automated plaque analysis was performed to quantify low attenuation plaque volume (density <30 HU), total non-calcified plaque volume (<150 HU, TNCPV) and remodeling index. The presence of the napkin-ring sign was assessed visually. The study endpoint was the occurrence of major adverse cardiac events (MACE), a composite of cardiac death, myocardial infarction and coronary revascularization more than 90 days after coronary CTA. RESULTS: During a clinical follow up of 5.7 years, MACE was observed in 46 patients (3.9%). All plaque characteristics were associated with MACE. The strongest association was observed for LAPV (HR 1.12, p < 0.0001). LAPV showed incremental prognostic value in a stepwise multivariable model including the Morise Score for clinical risk, calcium score and SSS (p = 0.036). CONCLUSION: LAPV, TPV, PR and presence of the napkin-ring sign are predictors of MACE independently of clinical risk presentation. LAPV carries slight additional prognostic information beyond the calcium score and conventional coronary CTA analysis. It may therefore improve risk prediction after CT imaging. PMID- 26837236 TI - A bio-inspired synthetic route to the core ring systems of Spiraea atisine-type diterpenoid alkaloids and related diterpenes. AB - A bio-inspired synthetic strategy for the efficient construction of the structurally complex azapentacyclic ABEFG ring systems of Spiraea atisine-type diterpenoid alkaloids bearing a characteristic internal carbinolamine ether linkage between C(7) and C(20) has been successfully developed. The highly bridged azapentacyclic core structure was constructed rapidly from a readily prepared trans-6,6-bicyclic AB ring precursor through a 14-step sequence. Highlights of the synthesis include a straightforward formal lactone migration from the tricyclic gamma-lactone unit of naturally occurring spiramilactone E, and an efficient biomimetic synthesis of the azapentacyclic ABEFG ring systems of spiramines C and D from the corresponding tetracyclic subunits of spiraminol and spiramilactone B. PMID- 26837237 TI - The influence of medial patellofemoral ligament reconstruction on clinical results and sports activity level. AB - OBJECTIVES: The aim of this study was to demonstrate postoperative outcomes and return to regular physical and sports activities at average of 6 years after patellar stabilization with medial patellofemoral ligament (MPFL) reconstruction. METHODS: Between November 2006 and January 2010, 31 isolated MPFL reconstructions in 29 patients with recurrent patellar dislocation were performed. Radiographs and magnetic resonance imaging were evaluated preoperatively. Knee function was assessed pre- and postoperative using Kujala score and the patient satisfaction, according to the International Knee Documentation Committee (IKDC) score. Tegner activity score was used for the evaluation of sports activity level. RESULTS: The average follow-up was 6.4+/-1.2 years. All measured scores increased significantly at follow-up. The average Kujala score increased from 75+/-10 to 95+/-10, patient satisfaction according to IKDC score from 6.1+/-1.4 to 8.7+/-1.4 and Tegner activity score from 4.4+/-1.6 to 5.7+/-1.3. The Tegner activity score after surgery was significantly lower than the score before the patellar dislocation (6.7+/-1.3). There were no significant differences in Kujala postoperative score between women's and men's group (P=0.25). There was no significant correlation between body mass index and Kujala score postoperatively (P=0.11) and between age at surgery and Kujala scores postoperatively (P=0.56). Patients who were active in sports preoperatively had resumed sports activities in 88.5% after surgery, 69.6% of them returned to the same levels and 30.4% return to the lower levels. CONCLUSION: Patellar stabilization with MPFL reconstruction is a safe and effective treatment method for all patients with patellofemoral instability and allows most patients to return to regular physical and sports activities after surgical intervention. Although sports activity level increased significantly after surgery, the same level of sports activity before the patellar dislocation has not been achieved. PMID- 26837238 TI - Effects of Combined Milrinone and Levosimendan Treatment on Systolic and Diastolic Function During Postischemic Myocardial Dysfunction in a Porcine Model. AB - It is not known whether there are positive or negative interactions on ventricular function when a calcium-sensitizing inotrope is added to a phosphodiesterase inhibitor in the clinical setting of acute left ventricular (LV) dysfunction. We hypothesized that when levosimendan is added to milrinone treatment, there will be synergetic inotropic and lusitropic effects. This was tested in an anesthetized porcine postischemic global LV injury model, where ventricular pressures and volumes (conductance volumetry) were measured. A global ischemic injury was induced by repetitive left main stem coronary artery occlusions. Load-independent indices of LV function were assessed before and after ventricular injury, after milrinone treatment, and finally after addition of levosimendan to the milrinone treatment. Nonparametric, within-group comparisons were made. The protocol was completed in 12 pigs, 7 of which received the inotrope treatment and 5 of which served as controls. Milrinone led to positive lusitropic effects seen by improvement in tau after myocardial stunning. The addition of levosimendan to milrinone further increased lusitropic state. The latter effect could however not be attributed solely to levosimendan, since lusitropic state also improved spontaneously in time-matched controls at the same rate during the corresponding period. When levosimendan was added to milrinone infusion, there was no increase in systolic function (preload recruitable stroke work) compared to milrinone treatment alone. We conclude that in this model of postischemic LV dysfunction, there appears to be no clear improvement in systolic or diastolic function after addition of levosimendan to established milrinone treatment but also no negative effects of levosimendan in this context. PMID- 26837239 TI - Impact of age on cytotoxic-induced ovarian failure in breast cancer treated with adjuvant chemotherapy and triptorelin. AB - AIM: This study analyzes our single-center, retrospective experience on 63 premenopausal breast cancer patients treated with monthly triptorelin and concomitant chemotherapy. PATIENTS & METHODS: Concomitant chemotherapy and triptorelin were adopted as part of premature ovarian failure prevention strategy. RESULTS: Age at diagnosis was the main factor influencing fertility preservation (p = 0.002). Compared with patients aged 41-45 years, the probability of menses resumption was almost threefold than for women aged 35-40 years, and significantly higher for women aged <35 years (hazard ratio: 9.0; p = 0.0001). The cumulative proportion among patients who resumed menses was 33.3% at 6 months, 75% at 12 months and 87.5% at 24 months. Seven patients attempted pregnancy, and five (71%) obtained healthy deliveries. CONCLUSION: We observed an acceptable rate of fertility preservation. Age at diagnosis influences fertility preservation. PMID- 26837240 TI - Active layers of high-performance lead zirconate titanate at temperatures compatible with silicon nano- and microeletronic [corrected] devices. AB - Applications of ferroelectric materials in modern microelectronics will be greatly encouraged if the thermal incompatibility between inorganic ferroelectrics and semiconductor devices is overcome. Here, solution-processable layers of the most commercial ferroelectric compound--morphotrophic phase boundary lead zirconate titanate, namely Pb(Zr0.52Ti0.48)O3 (PZT)--are grown on silicon substrates at temperatures well below the standard CMOS process of semiconductor technology. The method, potentially transferable to a broader range of Zr:Ti ratios, is based on the addition of crystalline nanoseeds to photosensitive solutions of PZT resulting in perovskite crystallization from only 350 degrees C after the enhanced decomposition of metal precursors in the films by UV irradiation. A remanent polarization of 10.0 MUC cm(-2) is obtained for these films that is in the order of the switching charge densities demanded for FeRAM devices. Also, a dielectric constant of ~90 is measured at zero voltage which exceeds that of current single-oxide candidates for capacitance applications. The multifunctionality of the films is additionally demonstrated by their pyroelectric and piezoelectric performance. The potential integration of PZT layers at such low fabrication temperatures may redefine the concept design of classical microelectronic devices, besides allowing inorganic ferroelectrics to enter the scene of the emerging large-area, flexible electronics. PMID- 26837242 TI - Induction of protective neutralizing antibody responses against botulinum neurotoxin serotype C using plasmid carried by PLGA nanoparticles. AB - Botulinum neurotoxin (BoNT) is a lethal neurotoxin, for which there is currently not an approved vaccine. Recent efforts in developing vaccine candidates against botulism have been directed at the heavy chain fragment of BoNT, because antibodies against this region have been shown to prevent BoNT from binding to its receptor and thus to nerve cell surface, offering protection against BoNT intoxication. In the present study, it was shown that immunization with plasmid DNA that encodes the 50 KDa C-terminal fragment of the heavy chain of BoNT serotype C (i.e., BoNT/C-Hc50) and is carried by cationic poly (lactic-co glycolic) acid (PLGA) nanoparticles induces stronger BoNT/C-specific antibody responses, as compared to immunization with the plasmid alone. Importantly, the antibodies have BoNT/C-neutralizing activity, protecting the immunized mice from a lethal dose of BoNT/C challenge. A plasmid DNA vaccine encoding the Hc50 fragments of BoNT serotypes that cause human botulism may represent a viable vaccine candidate for protecting against botulinum neurotoxin intoxication. PMID- 26837241 TI - IgG4 anti-phospholipase A2 receptor might activate lectin and alternative complement pathway meanwhile in idiopathic membranous nephropathy: an inspiration from a cross-sectional study. AB - The deposition of IgG4 of antibodies against phospholipase A2 receptor (anti PLA2R) is predominating in the kidneys of patients with idiopathic membranous nephropathy, while its predictive value has not been determined. It was a retrospective study, and 438 patients were included. Serum samples of two time points [before intervention (baseline) and after 1.5-year treatment (endpoint)] were detected for total and IgG4 anti-PLA2R. IgG4 <0.26 RU/mL or total <20 RU/mL was considered as seronegativity. Bi-positivity/bi-negativity was defined when patients'antibodies were found positive or negative both at the baseline and endpoint. Completed remission (CR) was a major clinical outcome. A series of complement ingredients (MASP-1/2, MBL, C3a, C5a, Factor B, Ba, Bb and C5b-9) were measured in the patients of bi-positivity and bi-negativity: (1) meta-analysis based on six papers conducted seropositivity of anti-PLA2R was a useful predictor for achieving CR, but there was a high heterogeneity; (2) there was significant correlation between the baseline and decrease in IgG4 subclass and the achievement of CR; (3) bi-negativity of IgG4 has a high accuracy of predicting CR compared with total antibodies; (4) in patients of bi-positivity, those achieving CR showed lower MASP-1/2, MBL, C3a, C5a, FB, Ba and Bb than patients failing to achieve CR; (5) the titers of endpoint and decrease in Ba and Bb were associated with improvement of 24 h-UP in those of bi-positivity; and (6) the decrease in Ba was a significant factor for achieving CR in those of bi-positivity. Continuous IgG4 negativity was a useful tool to predict the achievement of CR; however, in patients of continuous IgG4 positivity, those with lower activation of lectin and alternative pathways would still more probably achieve CR. PMID- 26837244 TI - [Lay emphasis on the treatment and exploration of extraordinary injuries]. AB - Treatment of "extraordinary injuries" is a major challenge for surgeons major in burn care and plastic surgery, though they are experts in wound treatment and repair. The "extraordinary injuries" is very complicated, and its treatment needs multidisciplinary cooperation. Surgeons not only have to master the relevant knowledge, but also should have the expertise to choose the appropriate treatment targeting the special pathological characteristics of the extraordinary wounds. Therefore, surgeons should learn and aggregate more knowledge regarding extraordinary injuries, strengthen muture communication, and encourage research work. PMID- 26837245 TI - [Enlightenment and deliberation after treatment for extraordinary injuries]. AB - With the development of modern society, the range of disease spectrum is changing, and risk factors leading to human trauma and damage are also in the shift. In addition to the extraordinary burns in the traditional sense, we also call extraordinary injury as damage induced by some of extraordinary insults in the past. In recent years, damage to skin and soft tissue caused by an extraordinary injury showed a gradually increasing trend. Manifestations of the wound of an extraordinary injury are various and its clinical treatment is very difficult, often requiring exceptional systemic comprehensive treatments. Currently, it is the duty of colleagues in the burn unit to actively deliberate about their realities regarding the following aspects: to accurately define the concept and scope of extraordinary injury, to include it into the range of clinical research and treatment of burns, to fully use professional skills of burn surgeons in dealing with wounds, and to effectively treat the patients through learning and mastering treatment skills of other clinical disciplines for treatment of extraordinary injury. PMID- 26837243 TI - Targeting Nonsquamous Nonsmall Cell Lung Cancer via the Proton-Coupled Folate Transporter with 6-Substituted Pyrrolo[2,3-d]Pyrimidine Thienoyl Antifolates. AB - Pemetrexed (PMX) is a 5-substituted pyrrolo[2,3-d]pyrimidine antifolate used for therapy of nonsquamous nonsmall cell lung cancer (NS-NSCLC). PMX is transported by the reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT). Unlike RFC, PCFT is active at acidic pH levels characterizing the tumor microenvironment. By real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, PCFT transcripts and proteins were detected in primary NS-NSCLC specimens. In six NS-NSCLC cell lines (A549, H1437, H460, H1299, H1650, and H2030), PCFT transcripts and proteins were detected by real-time RT PCR and western blots, respectively. 6-Substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates related to PMX [compound 1 (C1) and compound 2 (C2), respectively] are selective substrates for PCFT over RFC. In the NS-NSCLC cell lines, both [(3)H]PMX and [(3)H]C2 were transported by PCFT. C1 and C2 inhibited proliferation of the NS-NSCLC cell lines; A549, H460, and H2030 cells were more sensitive to C1 than to PMX. C1 and C2 inhibited glycinamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis. When treated at pH 6.8, which favors PCFT uptake, C1 and C2 inhibited clonogenicity of H460 cells greater than PMX; PMX inhibited clonogenicity more than C1 or C2 at pH 7.2, which favors RFC transport over PCFT. Knockdown of PCFT in H460 cells resulted in decreased [(3)H]PMX and [(3)H]C2 transport and decreased growth inhibition by C1 and C2, and to a lesser extent by PMX. In vivo efficacy of C1 was seen toward H460 tumor xenografts in severe-combined immunodeficient mice. Our results suggest that 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates offer significant promise for treating NS-NSCLC by selective uptake by PCFT. PMID- 26837246 TI - [Clinical application of modified skin soft tissue expansion in early repair of devastating wound on the head due to electrical burn]. AB - OBJECTIVE: To observe the clinical effect of modified skin soft tissue expansion in repair of devastating wound on the head due to electrical burn in the early stage. METHODS: Twenty-one patients with partial scalp soft tissue defect accompanying skull exposure and necrosis in different degree due to high-voltage electrical burn were hospitalized from April 2009 to October 2014, with wound area ranging from 7 cm * 5 cm to 15 cm * 13 cm. The wounds were debrided as early as possible, and necrotic skulls were kept in situ and covered with porcine ADM and silver-containing dressing. Bacterial culture of exudate from the residual soft tissue was carried out 3 days after hospitalization. Pertinent antibiotics were applied topically to control infection, and autologous split-thickness skin grafts were transplanted. Two to three weeks after injury when the skin grafts survived, modified skin soft tissue expansion was carried out. The crossbow-form incision was made on the normal scalp 2 cm away from the edge of transplanted skin; a capsule cavity was formed by ladder-like dissection. An expander was inserted with the injection port laying outside. The expander was stretched by inflation and deflation. The incisions were sutured layer by layer. The time of continuing negative pressure drainage in the interval of expansion was extended. Volume of water reaching 2 to 3 times of the capacity of expander was injected for excessive expanding. The expanded skin flap was rotated to repair the wound after expansion was ended. RESULTS: Within 1 week after debridement, 4 kinds of bacteria were detected in the bacterial culture of wound exudate, including 4 cases of Staphylococcus aureus, 5 cases of Staphylococcus epidermidis, 5 cases of Pseudomonas aeruginosa, and 3 cases of Acinetobacter baumannii. A total of 26 expanders were imbedded. No infection or incision dehiscence in the expanding area or cracking and leakage of expander was observed during expanding period. Two to three months after injury, expanded skin flap transplantation was completed, and the wound was repaired. Raw wounds were seen in 4 expanded skin flaps after transfer, and they healed after dressing change. Punctiform ulceration at the seams of 2 flaps was observed one month after the operation, which healed after removing few pieces of sequestra by themselves. The other expanded skin flaps survived well. During the postoperative follow-up for 3 to 12 months, satisfactory appearance and hair growth was observed in the operation area. CONCLUSIONS: Repair of the devastating wound on the head due to electrical burn with modified skin soft tissue expansion could achieve the result of early wound covering and cosmetic repair without alopecia in one time. PMID- 26837247 TI - [Treatment of 568 patients with frostbite in northeastern China with an analysis of rate of amputation]. AB - OBJECTIVE: To study the key points of treatment and amputation in patients with frostbite, so as to increase the successful rate of the treatment. METHODS: Five hundred and sixty-eight patients with frostbite admitted to our department from January 2005 to December 2014. (1) For the patients admitted to our department within one week after injury, the frostbite wounds were soaked in 42 degrees C herbal fluid (twice per day, 30 min for each time) and irradiated with infrared or red light (three times per day, 40 min for each time) from the day of admission to the 7th day after injury. Meanwhile, treatment for improvement of microcirculation, vasodilation, and anti-infection were also given. Then they received infrared or red light irradiation to the wound sites. For the patients admitted to our department longer than one week after frostbite, the frostbite wounds were irradiated with infrared or red light, and treated with antibiotics if inflammation was found around the wound. Among all the patients, 5 cases suffered from frozen stiff, and they were given fluid resuscitation as well as above-mentioned treatments after admission. (2) All patients were given wound treatment immediately after admission. The superficial partial-thickness wounds and deep partial-thickness wounds of 264 patients were given routine dressing change. The full-thickness wounds in 79 patients were treated with exposure therapy after routine dressing change first, and then granulation tissue of these wounds were grafted with autologous thigh split-thickness skin grafts. After debridement and exposure therapy, amputation was done in 225 patients 3 to 4 weeks after injury when the underlying bone was exposed. In 4 patients with exposure of calcaneus, the wounds were covered with reverse sural nerve nutrient vessels island flap. Mean healing time of superficial partial-thickness wound and deep partial-thickness wound, survival rate of skin graft in full-thickness wound, and survival rate of flap covering wound deep to bone at the heel were all recorded. The amputation rate of patients injured in December, January, February, and other months, that of patients admitted shorter than 1 day after frostbite, 1 to 3 days after frostbite, longer than 3 days and shorter than or equal to 5 days after frostbite, and longer than 5 days after frostbite, that of patients caused by drunkenness, mental disorders, improper protection, going astray, and trauma including traffic accident etc., and that of patients treated with rewarming under room temperature, rubbing with snow, wrapping with quilt, and soaking in warm water before admission were all recorded and analyzed. Parts of the data were processed with chi(2) test. RESULTS: All patients were survived after treatment. Average wound healing time of superficial partial -thickness wound and deep partial-thickness wound was respectively 10 and 23 days. The survival rate of skin graft on full-thickness wound was about 95%. Survival rate of flap on wound deep to bone at the heel was 100%. Amputation rates of patients injured in December and January were respectively 47.46% (84/177), 42.56% (103/242), and both were significantly higher than those of patients injured in February and the other months [respectively 29.55% (26/88), 13.11% (8/61), with chi(2) values from 42.595 to 220.900, P values below 0.01]. Amputation rate of patients with admission time shorter than 1 day after frostbite was 32.06% (84/262), which was obviously lower than that of patients with admission time from 1 to 3 days after frostbite, longer than 3 days and less than or equal to 5 days after frostbite, or longer than 5 days after frostbite [respectively 40.48% (68/168), 49.02% (50/102), 52.78% (19/36), with chi(2) values from 107.284 to 165.350, P values below 0.01]. Amputation rates of patients with frostbite occurring after getting drunkenness, mental disorders, and trauma including traffic accident etc. were respectively 42.06% (106/252), 43.48% (60/138), and 53.12% (17/32), and they were all significantly higher than those of patients with frostbite caused by improper protection and going astray [respectively 27.45% (28/102), 22.73% (10/44), with chi(2) values from 187.260 to 209.738, P values below 0.01]. Amputation rates of patients undergoing treatment of rewarming under room temperature, rubbing with snow, wrapping with quilt before admission were respectively 44.29% (62/140), 48.28% (84/174), and 35.38% (46/130), and they were significantly higher than the amputation rate of patients who received the treatment of soaking in warm water [23.39% (29/124), with chi(2) values from 97.364 to 136.189, P values below 0.01]. CONCLUSIONS: Early diagnosis and treatment, properly rewarming at early stage, and correct wound treatment are the key points for reducing amputation rate of patients after frostbite. Attention should be paid to the occurrence of frostbite in December and January, and also to protection of high-risk groups (patients with mental disorders and drunker). PMID- 26837248 TI - [Clinical observation on the treatment of phenol burn patients complicated by acute kidney injury with early blood purification]. AB - OBJECTIVE: To observe the clinical effects of early blood purification in the treatment of phenol burn patients complicated by acute kidney injury (AKI). METHODS: Five phenol burn patients complicated by AKI, matched with the inclusion criteria, were hospitalized from January 2010 to July 2014. Within post injury hour 24, patients received rapid liquid support, positive wound management, and hemoperfusion (HP) combined with continuous veno-venous hemofiltration (CVVH) for 2 to 3 hours, then HP was stopped and CVVH was continued for 16 to 21 hours. HP combined with CVVH was performed for 2 to 3 times, then HP was stopped and CVVH was continued for 12 to 22 days. On post injury day (PID) 1, 3, 5, 7, 14, and 21, urea nitrogen, creatinine, ALT, AST, total bilirubin (TBIL), direct bilirubin (DBIL) in serum were determined, and the volume of liquid intake, urine, ultrafiltration, and liquid output were recorded, and the concentrations of IL-6, IL-10 and TNF-alpha in serum were determined by ELISA. General conditions of patients were recorded. Data were processed with one-way analysis of variance and LSD- t test. RESULTS: (1) On PID 1, the levels of urea nitrogen and creatinine were (9.0 +/- 3.2) mmol/L and (115 +/- 24) umol/L respectively, which were obviously higher than normal values (with the values of 2.9-8.2 mmol/L and 45-104 umol/L respectively). On PID 3, 5, 7 and 21, the levels of urea nitrogen were (12.5 +/- 4.1), (11.2 +/- 5.6), (8.7 +/- 2.3) and (6.4 +/- 3.9) mmol/L respectively, which were similar with the value of DID 1 (with t values 1.53, 0.76, 0.17 and 1.17 respectively, P values above 0.05). On PID 14, the level of urea nitrogen was (15.8 +/- 3.3) mmol/L, which was obviously higher than the value of PID 1 (t =3 .29, P = 0.023). On PID 3, 5, 7 and 14, the levels of creatinine were (248 +/- 67), (224 +/- 87), (276 +/- 59) and (307 +/- 77) umol/L respectively, which were obviously higher than the value of PID 1 (with t values 4.17, 2.70, 5.65 and 5.32 respectively, P values below 0.01). On PID 21, the level of creatinine was (78 +/- 28) umol/L, which was obviously lower than the value of PID 1 (t = 2.23, P = 0.041). The levels of ALT, AST, TBIL, and DBIL were higher than normal values from PID 1, and the levels were higher than normal values on PID 3, 5, 7, and 14, and they were similar with the normal values on PID 21. (2) On PID 1, 3, 5, 7, 14, and 21, the volume ratio of liquid intake to liquid output maintained from1:1 to 2:1. On PID 1, 3, 5, 7, and 14, although the volume of urine fluctuated, they were still less than 400 mL/d, and the volume for ultrafiltration showed a tendency from declining at first to a rise later. On PID 21, the volume of urine increased, and the volume for ultrafiltration decreased. (3) On PID 1, the serum concentrations of TNF-alpha and IL-6 increased, and the serum concentration of IL-10 decreased. On PID 3, 5, and 7, the serum concentrations of TNF-alpha and IL-6 decreased, and the serum concentration of IL-10 increased. On PID 14, the serum concentrations of TNF alpha and IL-6 were elevated again but without a high peak value, and the serum concentration of IL-10 decreased but still higher than the value of PID 1. On PID 21, the serum concentrations of TNF-alpha and IL-6 obviously decreased, and the serum concentration of IL-10 obviously elevated. (4) Primary healing of the wound was achieved on PID 21 to 28. Patients were all cured and left hospital on PID 28 to 45. All the patients were followed up for 6 months to 3 years. At the last follow up, patients had no symptoms of chronic poisoning and the functions of liver and kidney were normal. CONCLUSIONS: Early blood purification treatment is effective for phenol patients phenol burn patients complicated by AKI, and wound healing and kidney function recovery were assured. PMID- 26837249 TI - [Repair of cervical postradiation ulcer following radical mastectomy with lower trapezius myocutaneous flap]. AB - OBJECTIVE: To explore the clinical effects of ipsilateral lower trapezius myocutaneous flap for repairing cervical ulcer as a result of radiotherapy after radical mastectomy. METHODS: Six patients with cervical ulcers as a result of radiotherapy after radical mastectomy were hospitalized from March 2010 to February 2015, suffering from persistent pain in different degrees. The wound area ranged from 6 cm * 4 cm to 10 cm * 6 cm before debridement, 8 cm * 5 cm to 16 cm * 10 cm after debridement. Ipsilateral lower trapezius myocutaneous flap was used to repair the wound after thorough debridement, with the area ranging from 10 cm * 7 cm to 20 cm * 13 cm. The donor sites were sutured directly or covered with medium-thickness skin graft obtained from the back. RESULTS: Pain was obviously relieved in all the patients 2 days after surgery. The wounds in five patients were healed, while necrosis of superficial skin approximately 1 cm in diameter appeared at the distal end of one myocutaneous flap, and it healed after dressing change. During the follow-up period of 3 to 18 months, no recurrence of ulcer was found, the texture of the myocutaneous flaps was soft with good appearance, and the donor sites healed well. CONCLUSIONS: On the basis of thorough debridement, it is feasible to repair the cervical ulcer as a result of radiotherapy after radical mastectomy with the ipsilateral lower trapezius myocutaneous flap. PMID- 26837250 TI - [Advances in the research of an animal model of wound due to Mycobacterium tuberculosis infection]. AB - Tuberculosis ranks as the second deadly infectious disease worldwide. The incidence of tuberculosis is high in China. Refractory wound caused by Mycobacterium tuberculosis infection ranks high in misdiagnosis, and it is accompanied by a protracted course, and its pathogenic mechanism is still not so clear. In order to study its pathogenic mechanism, it is necessary to reproduce an appropriate animal model. Up to now the study of the refractory wound caused by Mycobacterium tuberculosis infection is just beginning, and there is still no unimpeachable model for study. This review describes two models which may reproduce a wound similar to the wound caused by Mycobacterium tuberculosis infection, so that they could be used to study the pathogenesis and characteristics of a tuberculosis wound in an animal. PMID- 26837251 TI - [Effects of exogenous recombinant human basic fibroblast growth factor on the healing of muscles in rats after deep tissue injury of pressure ulcers]. AB - OBJECTIVE: To investigate the effect of exogenous recombinant human basic fibroblast growth factor (rhbFGF) on the healing of muscles in rats after deep tissue injury of pressure ulcers. METHODS: Forty-eight SD rats were randomly divided into normal control group, injury control group, post injury day (PID) 4 group, PID 7 group, PID 14 group, PID 21 group according to the random number table, with 8 rats in each group. The rats in normal control group did not receive any treatment, whereas the rats in the latter 5 groups were established the deep tissue injury of pressure ulcer model on both sides of the gracilis muscle on the hind limb. The rats in injury control group did not receive any treatment after injury, while the rats in the latter 4 groups were given subcutaneous injection of 0.1 mL rhbFGF to the left gracilis in a dosage of 100 ug/mL immediately after injury, and an equal volume of normal saline (NS) was injected to right gracilis, once every other day. The rats in injury control group were sacrificed immediately after injury, and the rats in normal control group were sacrificed at the same time point. The rats in the other 4 groups were sacrificed on PID 4, 7, 14, 21, and the gracilis muscles on both sides were harvested respectively. The morphology of the gracilis muscle was examined after HE staining. The expression of myogenin in the tissues was detected by immunofluorescence method. The levels of muscle structural proteins myosin heavy chain (MyHC), phosphorylated protein kinase B (Akt), and phosphorylated mammalian target of rapamycin (mTOR) were determined by Western blotting. Data were processed with one-way analysis of variance and LSD test. RESULTS: (1) In normal control group, the nuclei of graciles cells were in uniform size, and they were closely arranged with clear structure, and there were no significant infiltration of inflammatory cells. In injury control group, the nuclei of graciles cells showed signs of pyknosis, dissolution, fracture and structural disorder. Swelling of muscle cells, inflammation infiltration, structural disorder and other pathological signs of injury phenomena in graciles of PID 4 group, PID 7 group, PID 14 group, PID 21 group after rhbFGF treatment were milder compared with those after NS treatment. In addition, the numbers of regenerated myocytes in graciles of PID 4 group, PID 7 group, PID 14 group, PID 21 group after rhbFGF treatment were higher than those after NS treatment. (2) The numbers of graciles myogenin positive cells in normal control group and injury control group were respectively 28 +/- 17 and 42 +/- 28. The numbers of graciles myogenin positive cells in PID 4 group, PID 7 group, PID 14 group after NS treatment were 100 +/- 50, 196 +/- 87, 460 +/- 110 respectively, while the numbers of graciles myogenin positive cells in PID 4 group, PID 7 group, PID 14 group after rhbFGF treatment were 174 +/- 34, 717 +/- 182, 613 +/- 122 respectively, and the numbers of graciles myogenin positive cells after rhbFGF treatment were significantly higher than those after NS treatment in each group(P < 0.05 or P < 0.01). The number of graciles myogenin positive cells in PID 21 group after rhbFGF treatment was 109 +/- 34, which was significantly lower than that after NS treatment (218 +/- 71, P < 0.05). (3) The expression of MyHC in graciles in normal control group was high, which was decreased in injury control group. Both the expressions of MyHC in graciles in PID 4 group, PID 7 group, PID 14 group, PID 21 group after treatment of NS and rhbFGF showed a trend of gradual elevation, while the expressions of MyHC in graciles after rhbFGF treatment were significantly higher than those after NS treatment (P < 0.05 or P < 0.01). The expression of MyHC in graciles in PID 21 group showed a high level, and it was similar to that of the normal control group (P > 0.05). The expressions of phosphorylated Akt and phosphorylated mTOR in graciles of normal control group were low, and the expression of phosphorylated Akt in graciles increased in injury control group, while the expression of phosphorylated mTOR in graciles decreased in injury control group. The expressions of phosphorylated Akt and phosphorylated mTOR in graciles of PID 4 group, PID 7 group, PID 14 group, PID 21 group after treatment with rhbFGF showed a trend of elevation in the beginning but declined afterwards. The expressions of phosphorylated Akt and phosphorylated mTOR in graciles of PID 4 group after rhbFGF treatment were significantly lower than those after NS treatment (P <0 .05 or P < 0.01). The expressions of phosphorylated Akt and phosphorylated mTOR in graciles of PID 7 group, PID 14 group, PID 21 group after rhbFGF treatment were significantly higher than those after NS treatment (P < 0.05 or P < 0.01). CONCLUSIONS: Exogenous rhbFGF may effectively facilitate the healing of muscle structure and accelerate the regeneration of muscles in rats after deep tissue injury of pressure ulcers, and its mechanism may be related to the improvement of the expression of myogenin and enhancement of the expression of protein of muscle growth-related signaling pathways. PMID- 26837252 TI - [Biologic effects of different concentrations of putrescine on human umbilical vein endothelial cells]. AB - OBJECTIVE: To explore the effects of different concentrations of putrescine on proliferation, migration, and apoptosis of human umbilical vein endothelial cells (HUVECs). METHODS: HUVECs were routinely cultured in vitro. The 3rd to the 5th passage of HUVECs were used in the following experiments. (1) Cells were divided into 500, 1 000, and 5 000 ug/mL putrescine groups according to the random number table (the same grouping method was used for following grouping), with 3 wells in each group, which were respectively cultured with complete culture solution containing putrescine in the corresponding concentration for 24 h. Morphology of cells was observed by inverted optical microscope. (2) Cells were divided into 0.5, 1.0, 5.0, 10.0, 50.0, 100.0, 500.0, 1 000.0 ug/mL putrescine groups, and control group, with 4 wells in each group. Cells in the putrescine groups were respectively cultured with complete culture solution containing putrescine in the corresponding concentration for 24 h, and cells in control group were cultured with complete culture solution with no additional putrescine for 24 h. Cell proliferation activity (denoted as absorption value) was measured by colorimetry. (3) Cells were divided (with one well in each group) and cultured as in experiment (2), and the migration ability was detected by transwell migration assay. (4) Cells were divided (with one flask in each group) and cultured as in experiment (2), and the cell apoptosis rate was determined by flow cytometer. Data were processed with one-way analysis of variance, Kruskal-Wallis test, and Dunnett test. RESULTS: (1) After 24-h culture, cell attachment was good in 500 ug/mL putrescine group, and no obvious change in the shape was observed; cell attachment was less in 1 000 ug/mL putrescine group and the cells were small and rounded; cells in 5 000 ug/mL putrescine group were in fragmentation without attachment. (2) The absorption values of cells in 0.5, 1.0, 5.0, 10.0, 50.0, 100.0, 500.0, 1 000.0 ug/mL putrescine groups, and control group were respectively 0.588 +/- 0.055, 0.857 +/- 0.031, 0.707 +/- 0.031, 0.662 +/- 0.023, 0.450 +/- 0.019, 0.415 +/- 0.014, 0.359 +/- 0.020, 0.204 +/- 0.030, and 0.447 +/- 0.021, with statistically significant differences among them (chi(2) = 6.86, P = 0.009). The cell proliferation activity in 0.5, 1.0, 5.0, and 10.0 ug/mL putrescine groups was higher than that in control group (P < 0.05 or P < 0.01). The cell proliferation activity in 500.0 and 1 000.0 ug/mL putrescine groups was lower than that in control group (with P values below 0.01). The cell proliferation activity in 50.0 and 100.0 ug/mL putrescine groups was close to that in control group (with P values above 0.05). (3) There were statistically significant differences in the numbers of migrated cells between the putrescine groups and control group (F = 138.662, P < 0.001). The number of migrated cells was more in 1.0, 5.0, and 10.0 ug/mL putrescine groups than in control group (with P value below 0.01). The number of migrated cells was less in 500.0 and 1 000.0 ug/mL putrescine groups than in control group (with P value below 0.01). The number of migrated cells in 0.5, 50.0, and 100.0 ug/mL putrescine groups was close to that in control group (with P values above 0.05). (4) There were statistically significant differences in the apoptosis rate between the putrescine groups and control group (chi(2)=3.971, P=0.046). The cell apoptosis rate was lower in 0.5, 1.0, 5.0, and 10.0 ug/mL putrescine groups than in control group (with P values below 0.05). The cell apoptosis rate was higher in 500.0 and 1 000.0 ug/mL putrescine groups than in control group (with P values below 0.01). The cell apoptosis rates in 50.0 and 100.0 ug/mL putrescine groups were close to the cell apoptosis rate in control group (with P values above 0.05). CONCLUSIONS: Low concentration of putrescine can remarkably enhance the ability of proliferation and migration of HUVECs, while a high concentration of putrescine can obviously inhibit HUVECs proliferation and migration, and it induces apoptosis. PMID- 26837253 TI - [Advances in the application of extracorporeal membrane oxygenation in the treatment of severe burn]. AB - Extracorporeal membrane oxygenation (ECMO) is a kind of technique that uses extracorporeal circulation system to draw patients' blood into the circuit, and then oxygenate the blood when it passes along the membrane, followed by returning the blood into patients. At present, ECMO is mainly used in treating patients with respiratory failure and circulatory failure, for whom the conventional treatment such as mechanical ventilation and vasoactive drugs are invalid. ECMO can provide cardiopulmonary support for burn patients with respiratory failure or circulatory failure, and put the heart and lung at rest. The purpose of this paper is to review the application of ECMO in the treatment of severe burn. PMID- 26837254 TI - [Debridement of burn wounds using a hydrosurgery system]. AB - The healing process of burn wounds is strongly associated with the depth of wounds, and the depth of wounds is dependent to initial temperature and duration of contact with source of heat, infection, and secondary damage in the debridement process. On this basis, some experts present a concept of accurate debridement, which denotes removal of all necrotic tissue and at the same time protecting viable tissue for repair of raw wounds in order to maximally maintain patients' appearance and functions. A new technology of burn wound debridement- hydrosurgery system has been applied clinically. This paper summarizes the characteristics of hydrosurgery in the aspects of its technology, suitable wounds, bacterial load, amount of blood loss, and degree of pain produced during operation, and also the author's opinions regarding its efficacy to realize an accurate debridement for burn injury. PMID- 26837255 TI - [Advances in the research of mechanisms of promotion of vascularization by angiogenin and its application]. AB - Angiogenin, as a member of the ribonuclease superfamily, is an angiogenic protein. The angiogenic ability of angiogenin plays an important role in many physical and pathological processes. Angiogenin can induce endothelial cell migration, proliferation, tubulation, as well as inhibition of cellular apoptosis. Angiogenin can be used to modulate the angiogenetic process of tissue engineered constructions via local delivery. Furthermore, angiogenin can also be regarded as a biomarker for diagnostic evaluation of malignancy, or as a target for cancer therapy. This paper presents a comprehensive overview of the angiogenic mechanisms of angiogenin, as well as its potential application in the process of wound healing and treatment of ischemic diseases and malignancy. PMID- 26837256 TI - [Advances in the mechanism of mesenchymal stem cells in promoting wound healing]. AB - Mesenchymal stem cells possess the ability of self-renewal and multiple differentiation potential, thus exert immunomodulatory effect during tissue repair. Mesenchymal stem cells can stimulate angiogenesis and promote tissue repair through transdifferentiation and secreting a variety of growth factors and cytokines. This review outlines the advances in the mechanism of mesenchymal stem cells in promoting wound healing, including alleviation of inflammatory response, induction of angiogenesis, and promotion of migration of mesenchymal stem cells to the site of tissue injury. PMID- 26837257 TI - Vein harvesting and techniques for infrainguinal bypass. AB - In order to achieve good long term results after bypass surgery, alongside with good inflow and outflow arteries, the bypass graft material also has an important role. The best patency and limb salvage rates are achieved with autologous vein. If great saphenous vein is not available, acceptable long-term results can be achieved with arm veins and lesser saphenous vein. The quality and size of the vein are important. A small-caliber vein, increased wall thickness, postphlebitic changes and varicosities are associated with a risk of early failure. Preoperative vein mapping with ultrasound reduces readmissions and postoperative surgical site infections. During the mapping, the vein to be used and its main tributaries are marked with a permanent marker pen. To reduce wound complication rates we recommend bridged incisions in vein harvesting. Endoscopic vein harvesting seems to have no benefit compared to open techniques in lower limb bypasses, and has been associated with higher risk of primary patency loss at one year. With deep tunneling of the graft the problems caused by wound infection can be avoided. PMID- 26837258 TI - Precision medical and surgical management for thoracic aortic aneurysms and acute aortic dissections based on the causative mutant gene. AB - Almost one-quarter of patients presenting with thoracic aortic aneurysms (TAAs) or acute aortic dissections (TAADs) have an underlying mutation in a specific gene. A subset of these patients will have systemic syndromic features, for example, skeletal features in patients with Marfan Syndrome. It is important to note that the majority of patients with thoracic aortic disease will not have these syndromic features but many will have a family history of the disease. The genes predisposing to these thoracic aortic diseases are inherited in an autosomal dominant manner, and thirteen genes have been identified to date. As the clinical phenotype associated with each specific gene is defined, the data indicate that the underlying gene dictates associated syndromic features. More importantly, the underlying gene also dictates the aortic disease presentation, the risk for dissection at a given range of aortic diameters, the risk for additional vascular diseases and what specific vascular diseases occur associated with the gene. These results lead to the recommendation that the medical and surgical management of these patients be dictated by the underlying gene, and for patients with mutations in ACTA2, the specific mutation in the gene. PMID- 26837259 TI - Osteoarthritis in the hands of Michelangelo Buonarroti. PMID- 26837260 TI - Highly robust crystalsome via directed polymer crystallization at curved liquid/liquid interface. AB - Lipids and amphiphilic block copolymers spontaneously self-assemble in water to form a plethora of micelles and vesicles. They are typically fluidic in nature and often mechanically weak for applications such as drug delivery and gene therapeutics. Mechanical properties of polymeric materials could be improved by forming crystalline structures. However, most of the self-assembled micelles and vesicles have curved surfaces and precisely tuning crystallization within a nanoscale curved space is challenging, as the curved geometry is incommensurate with crystals having three-dimensional translational symmetry. Herein, we report using a miniemulsion crystallization method to grow nanosized, polymer single crystal-like capsules. We coin the name crystalsome to describe this unique structure, because they are formed by polymer lamellar crystals and their structure mimics liposomes and polymersomes. Using poly(L-lactic acid) (PLLA) as the model polymer, we show that curved water/p-xylene interface formed by the miniemulsion process can guide the growth of PLLA single crystals. Crystalsomes with the size ranging from ~148 nm to over 1 MUm have been formed. Atomic force microscopy measurement demonstrate a two to three orders of magnitude increase in bending modulus compared with conventional polymersomes. We envisage that this novel structure could shed light on investigating spherical crystallography and drug delivery. PMID- 26837261 TI - The simultaneous enhancement of photorefraction and optical damage resistance in MgO and Bi2O3 co-doped LiNbO3 crystals. AB - For a long time that optical damage was renamed as photorefraction, here we find that the optical damage resistance and photorefraction can be simultaneously enhanced in MgO and Bi2O3 co-doped LiNbO3 (LN:Bi,Mg). The photorefractive response time of LN:Bi,Mg was shortened to 170 ms while the photorefractive sensitivity reached up to 21 cm(2)/J. Meanwhile, LN:Bi,Mg crystals could withstand a light intensity higher than 10(6) W/cm(2) without apparent optical damage. Our experimental results indicate that photorefraction doesn't equal to optical damage. The underground mechanism was analyzed and attributed to that diffusion dominates the transport process of charge carriers, that is to say photorefraction causes only slight optical damage under diffusion mechanism, which is very important for the practical applications of photorefractive crystals, such as in holographic storage, integrated optics and 3D display. PMID- 26837262 TI - How Does the Gibbs Inequality Condition Affect the Stability and Detachment of Floating Spheres from the Free Surface of Water? AB - Floating objects on the air-water interfaces are central to a number of everyday activities, from walking on water by insects to flotation separation of valuable minerals using air bubbles. The available theories show that a fine sphere can float if the force of surface tension and buoyancies can support the sphere at the interface with an apical angle subtended by the circle of contact being larger than the contact angle. Here we show that the pinning of the contact line at the sharp edge, known as the Gibbs inequality condition, also plays a significant role in controlling the stability and detachment of floating spheres. Specifically, we truncated the spheres with different angles and used a force sensor device to measure the force of pushing the truncated spheres from the interface into water. We also developed a theoretical modeling to calculate the pushing force that in combination with experimental results shows different effects of the Gibbs inequality condition on the stability and detachment of the spheres from the water surface. For small angles of truncation, the Gibbs inequality condition does not affect the sphere detachment, and hence the classical theories on the floatability of spheres are valid. For large truncated angles, the Gibbs inequality condition determines the tenacity of the particle meniscus contact and the stability and detachment of floating spheres. In this case, the classical theories on the floatability of spheres are no longer valid. A critical truncated angle for the transition from the classical to the Gibbs inequality regimes of detachment was also established. The outcomes of this research advance our understanding of the behavior of floating objects, in particular, the flotation separation of valuable minerals, which often contain various sharp edges of their crystal faces. PMID- 26837264 TI - Controversies surrounding percutaneous coronary intervention in the diabetic patient. AB - Diabetic patients with coronary artery disease are common and complex, with an aggressive progression of atherosclerosis, increased rate of stent complications, and increased rates of incomplete revascularization in multivessel disease compared to non-diabetic patients. In this review, we first discuss the pathophysiologic elements of insulin resistance and presentations of coronary artery disease in diabetic patients. Next, we outline the evolution and present the data on revascularization strategies on diabetic patient outcomes. The overall conclusion of our review is that a strategy of complete and durable revascularization and guideline-directed medical therapy currently provides the best possible chance at closing the gap between outcomes in patients with and without diabetes. PMID- 26837263 TI - Predicting the Mutating Distribution at Antigenic Sites of the Influenza Virus. AB - Mutations of the influenza virus lead to antigenic changes that cause recurrent epidemics and vaccine resistance. Preventive measures would benefit greatly from the ability to predict the potential distribution of new antigenic sites in future strains. By leveraging the extensive historical records of HA sequences for 90 years, we designed a computational model to simulate the dynamic evolution of antigenic sites in A/H1N1. With templates of antigenic sequences, the model can effectively predict the potential distribution of future antigenic mutants. Validation on 10932 HA sequences from the last 16 years showing that the mutated antigenic sites of over 94% of reported strains fell in our predicted profile. Meanwhile, our model can successfully capture 96% of antigenic sites in those dominant epitopes. Similar results are observed on the complete set of H3N2 historical data, supporting the general applicability of our model to multiple sub-types of influenza. Our results suggest that the mutational profile of future antigenic sites can be predicted based on historical evolutionary traces despite the widespread, random mutations in influenza. Coupled with closely monitored sequence data from influenza surveillance networks, our method can help to forecast changes in viral antigenicity for seasonal flu and inform public health interventions. PMID- 26837265 TI - Nanoparticle-enhanced synergistic HIFU ablation and transarterial chemoembolization for efficient cancer therapy. AB - High-intensity focused ultrasound (HIFU) is being generally explored as a non invasive therapeutic modality to treat solid tumors. However, the clinical use of HIFU for large and deep tumor-ablation applications such as hepatocellular carcinoma (HCC) is currently entangled with long treatment duration and high operating energy. This critical issue can be potentially resolved by the introduction of HIFU synergistic agents (SAs). Traditional SAs such as microbubbles and microparticles face the problem of large size, short cycle time, damage to mononuclear phagocytic system and unsatisfactory targeting efficiency. In this work, we have developed a facile and versatile nanoparticle-based HIFU synergistic cancer surgery enhanced by transarterial chemoembolization for high efficiency HCC treatment based on elaborately designed Fe3O4-PFH/PLGA nanocapsules. Multifunctional Fe3O4-PFH/PLGA nanocapsules were administrated into tumor tissues via transarterial injection combined with Lipiodol to achieve high tumor accumulation because transarterial chemoembolization by Lipiodol could block the blood vessels. The high synergistic HIFU ablation effect was successfully achieved against HCC tumors based on the phase-transformation performance of the perfluorohexane (PFH) inner core in the composite nanocapsules, as systematically demonstrated in VX2 liver tumor xenograft in rabbits. Multifunctional Fe3O4-PFH/PLGA nanocapsules were also demonstrated as efficient contrast agents for ultrasound, magnetic resonance and photoacoustic tri-modality imagings, potentially applicable for imaging-guided HIFU synergistic surgery. Therefore, the elaborate integration of traditional transarterial chemoembolization with recently developed nanoparticle-enhanced HIFU cancer surgery could efficiently enhance the HCC cancer treatment outcome, initiating a new and efficient therapeutic protocol/modality for clinic cancer treatment. PMID- 26837266 TI - IL-17 in Chronic Inflammation: From Discovery to Targeting. AB - Interleukin-17 (IL-17) is a cytokine which elicits protection against extracellular bacterial and fungal infections and which plays important roles in inflammation. However, when produced in excess, it contributes to chronic inflammation associated with many inflammatory and autoimmune disorders. This has made IL-17 an attractive therapeutic target. The present review describes the structure of the IL-17 family, the IL-17 receptor complex, and the cells producing IL-17. The contributions of IL-17 to disease as well as new IL-17-based treatment options are discussed. Finally, the results of IL-17 or IL-17 receptor inhibitors in clinical trials are detailed. With a fruitful outlook, drug registration has now been granted for psoriasis psoriatic arthritis and ankylosing spondylitis, and also bears great potential in a growing number of conditions. PMID- 26837269 TI - Assessment of anthropogenic inputs in the surface waters of the southern coastal area of Sfax during spring (Tunisia, Southern Mediterranean Sea). AB - The coastal marine area of Sfax (Tunisia), which is well-known for its high productivity and fisheries, is also subjected to anthropogenic inputs from diverse industrial, urban and agriculture activities. We investigated the spatial distribution of physical, chemical and biogeochemical parameters in the surface waters of the southern coastal area of Sfax. Pertinent tracers of anthropogenic inputs were identified. Twenty stations were sampled during March 2013 in the vicinity of the coastal areas reserved for waste discharge. Phosphogypsum wastes dumped close to the beaches were the main source of PO4(3-), Cl(-) and SO4(2-) in seawater. The high content in total polyphenolic compounds was due to the olive oil treatment waste water released from margins. These inorganic and organic inputs in the surface waters were associated with elevated COD. The BOD5/COD (<0.5) and COD/BOD5 (>3) ratios highlighted a chemical pollution with organic load of a low biodegradability. PMID- 26837267 TI - Endothelial Dicer promotes atherosclerosis and vascular inflammation by miRNA-103 mediated suppression of KLF4. AB - MicroRNAs regulate the maladaptation of endothelial cells (ECs) to naturally occurring disturbed blood flow at arterial bifurcations resulting in arterial inflammation and atherosclerosis in response to hyperlipidemic stress. Here, we show that reduced endothelial expression of the RNAse Dicer, which generates almost all mature miRNAs, decreases monocyte adhesion, endothelial C-X-C motif chemokine 1 (CXCL1) expression, atherosclerosis and the lesional macrophage content in apolipoprotein E knockout mice (Apoe(-/-)) after exposure to a high fat diet. Endothelial Dicer deficiency reduces the expression of unstable miRNAs, such as miR-103, and promotes Kruppel-like factor 4 (KLF4)-dependent gene expression in murine atherosclerotic arteries. MiR-103 mediated suppression of KLF4 increases monocyte adhesion to ECs by enhancing nuclear factor-kappaB dependent CXCL1 expression. Inhibiting the interaction between miR-103 and KLF4 reduces atherosclerosis, lesional macrophage accumulation and endothelial CXCL1 expression. Overall, our study suggests that Dicer promotes endothelial maladaptation and atherosclerosis in part by miR-103-mediated suppression of KLF4. PMID- 26837270 TI - Seasonal distribution of aliphatic hydrocarbons in the Vaza Barris Estuarine System, Sergipe, Brazil. AB - The seasonal assessment of anthropogenic activities in the Vaza Barris estuarine river system, located in the Sergipe state, northeastern Brazil, was performed using the aliphatic hydrocarbon distribution. The aliphatic hydrocarbon and isoprenoid (Pristane and Phytane) concentrations ranged between 0.19 MUg g(-1) and 8.5 MUg g(-1) of dry weight. Data were analyzed using Kruskal-Wallis test, with significance level set at p<0.05, and no seasonality distribution change was observed. The Carbon Preference Index (CPI), associated with n-alkanes/n C16, Low Molecular Weight/High Molecular Weight ratio (LMW/HMW) and Terrigenous to Aquatic Ratio (TAR) suggested biogenic input of aliphatic hydrocarbons for most samples, with significant contribution of higher plants. PMID- 26837268 TI - Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis. AB - BACKGROUND: The impact of subclinical hypothyroidism (SCH) and of levothyroxine replacement in pregnant women with SCH is unclear. The aims of this study were to assess (i) the impact of SCH during pregnancy on maternal and neonatal outcomes, and (ii) the effect of levothyroxine replacement therapy in these patients. METHODS: Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, the Cochrane Controlled Trials Register, Ovid EMBASE, Web of Science, and Scopus were searched from inception to January 2015. Randomized trials and cohort studies of pregnant women with SCH that examined adverse pregnancy and neonatal outcomes were included. Reviewers extracted data and assessed methodological quality in duplicate. Eighteen cohort studies at low-to-moderate risk of bias were included. Compared with euthyroid pregnant women, pregnant women with SCH were at higher risk for pregnancy loss (relative risk [RR] 2.01 [confidence interval (CI) 1.66 2.44]), placental abruption (RR 2.14 [CI 1.23-3.70]), premature rupture of membranes (RR 1.43 [CI 1.04-1.95]), and neonatal death (RR 2.58 [CI 1.41-4.73]). One study at high risk of bias compared pregnant women with SCH who received levothyroxine to those who did not and found no significant decrease in the rate of pregnancy loss, preterm delivery, gestational hypertension, low birth weight, or low Apgar score. CONCLUSIONS: SCH during pregnancy is associated with multiple adverse maternal and neonatal outcomes. The value of levothyroxine therapy in preventing these adverse outcomes remains uncertain. PMID- 26837271 TI - Identifications and seasonal variations of sources of polycyclic aromatic hydrocarbons (PAHs) in the Yangtze River Estuary, China. AB - In this study, positive matrix factorization models (PMFx) were used to analyze the sources of sedimentary PAHs in Yangtze River Estuary (YRE) using 120 data samples from 30 sites collected over four seasons. Three sources were defined for the PAHs: coal and gasoline combustion was the dominant source, accounting for approximately 50%; coke plant emissions and wood or grass combustion each contributed approximately 25%. The coal tar origin was the major source in summer; wood or grass combustion dominated in autumn; coal combustion was the primary source of PAHs in spring and winter. More than 90% of the coke plant emissions were from summer, while pollutants from wood or grass combustion were discharged primarily in autumn. These three sources distributed in different primary regions, the spatial patterns of coal combustion presented an increasing trend in the seaward direction. PMID- 26837272 TI - Genetic architecture of adaptation to novel environmental conditions in a predominantly selfing allopolyploid plant. AB - Genetic architecture of adaptation is traditionally studied in the context of local adaptation, viz. spatially varying conditions experienced by the species. However, anthropogenic changes in the natural environment pose a new context to this issue, that is, adaptation to an environment that is new for the species. In this study, we used crossbreeding to analyze genetic architecture of adaptation to conditions not currently experienced by the species but with high probability of encounter in the near future due to global climate change. We performed targeted interpopulation crossing using genotypes from two core and two peripheral Triticum dicoccoides populations and raised the parents and three generations of hybrids in a greenhouse under simulated desert conditions to analyze the genetic architecture of adaptation to these conditions and an effect of gene flow from plants having different origin. The hybrid (F1) fitness did not differ from that of the parents in crosses where both plants originated from the species core, but in crosses involving one parent from the species core and another one from the species periphery the fitness of F1 was consistently higher than that of the periphery-originated parent. Plant fitness in the next two generations (F2 and F3) did not differ from the F1, suggesting that effects of epistatic interactions between recombining and segregating alleles of genes contributing to fitness were minor or absent. The observed low importance of epistatic gene interactions in allopolyploid T. dicoccoides and low probability of hybrid breakdown appear to be the result of permanent fixation of heterozygosity and lack of intergenomic recombination in this species. At the same time, predominant but not complete selfing combined with an advantage of bivalent pairing of homologous chromosomes appears to maintain high genetic variability in T. dicoccoides, greatly enhancing its adaptive ability. PMID- 26837275 TI - Transcriptional Profiles from Paired Normal Samples Offer Complementary Information on Cancer Patient Survival--Evidence from TCGA Pan-Cancer Data. AB - Although normal tissue samples adjacent to tumors are sometimes collected from patients in cancer studies, they are often used as normal controls to identify genes differentially expressed between tumor and normal samples. However, it is in general more difficult to obtain and clearly define paired normal samples, and whether these samples should be treated as "normal" due to their close proximity to tumors. In this article, by analyzing the accrued data in The Cancer Genome Atlas (TCGA), we show the surprising results that the paired normal samples are in general more informative on patient survival than tumors. Different lines of evidence suggest that this is likely due to tumor micro-environment instead of tumor cell contamination or field cancerization effect. Pathway analyses suggest that tumor micro-environment may play an important role in cancer patient survival either by boosting the adjacent metabolism or the in situ immunization. Our results suggest the potential benefit of collecting and profiling matched normal tissues to gain more insights on disease etiology and patient progression. PMID- 26837274 TI - Pre-ablation stimulated thyroglobulin is a better predictor of recurrence in pathological N1a papillary thyroid carcinoma than the lymph node ratio. AB - BACKGROUND: Papillary thyroid carcinomas (PTC) with lymph node metastases have a high recurrence rate. We analyzed the potential of lymph node ratio (LNR) and the level of pre-ablation stimulated thyroglobulin (sTg) as risk factors predicting recurrence in patients with pathological N1a PTC. MATERIALS AND METHODS: This study involved 192 patients with pathologically confirmed PTC and central neck lymph node metastases who underwent total thyroidectomy with central lymph node dissection (CLND). The clinico-pathological characteristics, the pre-ablation sTg level and post-treatment recurrences were examined. Univariate and multivariate analyses were performed to identify factors associated with recurrence in these patients. RESULTS: During a median follow-up of 63 months, 17 patients had loco regional recurrences. Receiver operating characteristic curve analysis showed that the appropriate cut-off values for LNR and the pre-ablation sTg level was 0.48 and 9.3 ng/mL, respectively. Patients with LNR values of >=0.48 had a significantly worse disease-free survival (DFS) than those with LNR values of <0.48 (P = 0.015), and patients with pre-ablation sTg level values of >=9.3 ng/mL had significantly worse DFS than those with pre-ablation sTg level values <9.3 ng/mL (P < 0.001). Relative to patients with LNR values of <0.48, those with LNR values of >=0.48 had higher median pre-ablation sTg level values (0.55 vs. 4.20; P < 0.001). The correlation covariant between the LNR value and the pre-ablation sTg level value was r = 0.454 (P < 0.001). Multivariate analysis showed that a LNR value of >=0.48 (P = 0.386) was not an independent risk factor for recurrence. To the contrary, a pre-ablation sTg level value of >=9.3 ng/mL (P < 0.001) was an independent risk factor for recurrence. CONCLUSION: A high pre ablation sTg level is a better predictor of recurrence in pathological N1a PTC than a high LNR value. Careful follow-up of patients with this risk factor is recommended. PMID- 26837273 TI - The genome of an Encephalitozoon cuniculi type III strain reveals insights into the genetic diversity and mode of reproduction of a ubiquitous vertebrate pathogen. AB - Encephalitozoon cuniculi is a model microsporidian species with a mononucleate nucleus and a genome that has been extensively studied. To date, analyses of genome diversity have revealed the existence of four genotypes in E. cuniculi (EcI, II, III and IV). Genome sequences are available for EcI, II and III, and are all very divergent, possibly diploid and genetically homogeneous. The mechanisms that cause low genetic diversity in E. cuniculi (for example, selfing, inbreeding or a combination of both), as well as the degree of genetic variation in their natural populations, have been hard to assess because genome data have been so far gathered from laboratory-propagated strains. In this study, we aim to tackle this issue by analyzing the complete genome sequence of a natural strain of E. cuniculi isolated in 2013 from a steppe lemming. The strain belongs to the EcIII genotype and has been designated EcIII-L. The EcIII-L genome sequence harbors genomic features intermediate to known genomes of II and III lab strains, and we provide primers that differentiate the three E. cuniculi genotypes using a single PCR. Surprisingly, the EcIII-L genome is also highly homogeneous, harbors signatures of heterozygosity and also one strain-specific single-nucleotide polymorphism (SNP) that introduces a stop codon in a key meiosis gene, Spo11. Functional analyses using a heterologous system demonstrate that this SNP leads to a deficient meiosis in a model fungus. This indicates that EcIII-L meiotic machinery may be presently broken. Overall, our findings reveal previously unsuspected genome diversity in E. cuniculi, some of which appears to affect genes of primary importance for the biology of this pathogen. PMID- 26837276 TI - Quadruplex Turncoats: Cation-Dependent Folding and Stability of Quadruplex-DNA Double Switches. AB - Quadruplex (G4) nucleic acids, a family of secondary structures formed by guanine rich sequences, exhibit an important structural polymorphism. We demonstrate here that G-rich DNA sequences may function as a double switch based on different triggers, provided that their quadruplex structures and stability display a high dependence on cation nature and concentration. A first switch is based on a remarkable antiparallel-to-parallel conversion, taking place in a few seconds at room temperature by addition of low KCl amounts to a sodium-rich sample. The second switch involves the conversion of alternative antiparallel quadruplex structures binding only one cation, formed in the presence of sub-millimolar potassium or strontium concentrations, to parallel structures by increasing the cation concentration. Incidentally, extremely low K(+) or Sr(2+) concentrations (<=5 equiv) are sufficient to induce G4 formation in a buffer devoid of other G4 promoting cations, and we suggest that the alternative structures observed contain only two tetrads. Such DNA systems are biological relevant targets, can be used in nanotechnology applications, and are valuable methodological tools for understanding DNA quadruplex folding, notably at low cation concentrations. We demonstrate that this behavior is not restricted to a narrow set of sequences but can also be found for other G-quadruplex-forming motifs, arguing for widespread applications. PMID- 26837277 TI - Study of tribological behavior of Cu-MoS2 and Ag-MoS2 nanocomposite lubricants. AB - Tribological behavior of Cu-MoS2 and Ag-MoS2 nanocomposite lubricant was studied. Cu nanoparticles produced by electrical explosion of copper wires and Ag nanoparticles prepared by electrospark erosion were employed as metal cladding modifiers of MoS2 nanolamellar particles. The tribological tests showed Cu-MoS2 and Ag-MoS2 nanocomposite lubricants changed the friction coefficient of the initial grease and essentially improved its wear resistance. PMID- 26837278 TI - Ru-catalyzed asymmetric hydrogenation of delta-keto Weinreb amides: enantioselective synthesis of (+)-Centrolobine. AB - An efficient asymmetric hydrogenation of delta-keto Weinreb amides catalyzed by a Ru-Xyl-SunPhos-Daipen bifunctional catalyst has been achieved. This method afforded a series of enantio-enriched delta-hydroxy Weinreb amides in good yields (up to 93%) and enantioselectivities (up to 99%). This protocol was successfully applied to the synthesis of the key intermediate of (+)-Centrolobine. PMID- 26837279 TI - Platinum phosphinothiolato hydride complexes: synthesis, structure and evaluation as tin-free hydroformylation catalysts. AB - Ligand 2-diphenylphosphinothiophenol (Hsarp) reacted with Pt(PPh3)4 to yield trans-[PtH(sarp)(PPh3)], which undergoes fast exchange with free PPh3 on the NMR time scale and very slowly and reversibly formed some cis-[PtH(sarp)(PPh3)] over time in solution (11%, 24 h). Reaction of trans-[PtH(sarp)(PPh3)] with Hsarp in boiling toluene gave cis- and trans-[Pt(sarp)2]; the cis isomer being more stable. These complexes were characterized by (1)H and (31)P NMR and also analyzed by XRD in the case of trans-[PtH(sarp)(PPh3)], trans-[Pt(sarp)2], and cis-[Pt(sarp)2]. trans-[PtH(sarp)(PPh3)] was evaluated as a preformed, tin-free hydroformylation catalyst on styrene and found active at 100 degrees C, at pressures over 75 bar, yielding phenylpropanal (regioselectivities up to 83% in 2 phenylpropanal), with total conversions to aldehydes up to 100% at styrene/platinum ratios from 400/1 to 1000/1 and minimal hydrogenation products. PMID- 26837280 TI - MicroRNA-130b improves renal tubulointerstitial fibrosis via repression of Snail induced epithelial-mesenchymal transition in diabetic nephropathy. AB - MicroRNA-130b (miR-130b) downregulation has been identified in diabetes, but the role and mechanisms for miR-130b in mediating renal tubulointerstitial fibrosis in diabetic nephropathy (DN) remain unknown. We demonstrated that plasma miR-130b downregulation exhibited clinical and biological relevance as it was linked to increased serum creatinine, beta2-microglobulin and proteinuria, increased Snail expression and tubulointerstitial fibrosis in renal biopsies of DN patients. MiR 130b inhibitor caused Snail upregulation and enhanced molecular features of epithelial-to-mesenchymal transition (EMT) in high glucose (30 mM) cultured NRK 52E cells. In contrast, miR-130b mimic downregulated Snail expression and increased epithelial hallmarks. Notably, Snail was identified as an miR-130b direct target and inversely correlated with E-CADHERIN expression. Furthermore, the miR-130b-dependent effects were due to Snail suppression that in turn deregulated E-CADHERIN, VIMENTIN, COLLAGEN IV and alpha-smooth muscle actin (alpha-SMA), key mediators of EMT. These effects were reproduced in streptozotocin-induced diabetic rats. Thus, we propose a novel role of the miR 130b-SNAIL axis in fostering EMT and progression toward increased tubulointerstitial fibrosis in DN. Detection of plasma miR-130b and its association with SNAIL can be extrapolated to quantifying the severity of renal tubulointerstitial fibrosis. Targeting miR-130b could be evaluated as a potential therapeutic approach for DN. PMID- 26837281 TI - Trends in Follow-Up of Patients Presenting to the Emergency Department with Symptomatic Cholelithiasis. AB - BACKGROUND: Fewer than 25% of Medicare beneficiaries presenting with symptomatic cholelithiasis undergo elective cholecystectomy. To better understand underuse of cholecystectomy, we examined physician follow-up patterns after emergency department (ED) visits for symptomatic gallstones. STUDY DESIGN: We used 100% Texas Medicare claims (2001 to 2010) to identify patients 66 years of age and older who presented to the ED with symptomatic cholelithiasis and were discharged home without cholecystectomy. Timing of outpatient physician visits after ED discharge and rates of emergent cholecystectomy based on physician follow-up patterns were compared. RESULTS: In total, 11,126 patients presented to the ED with symptomatic cholelithiasis and were discharged without cholecystectomy. After discharge, 5,327 patients (47.9%) had an outpatient surgeon visit, 29.0% saw another physician and never saw a surgeon, and 23.1% never saw a physician; 68.2% of patients who saw a surgeon underwent elective cholecystectomy; and 8.3% of patients who saw a surgeon, 14.6% of patients who saw other physicians and no surgeon, and 77.6% of patients who never saw any physician, required emergent hospitalization (p < 0.0001). For people who did not see a physician, mean time to emergent hospitalization was 7.5 days (median 2 days); 95.9% presented within 2 weeks after their initial presentation. CONCLUSIONS: Fewer than half of patients were evaluated by a surgeon after an initial ED visit for symptomatic gallstones. Patients who did not have physician follow-up were most likely to require emergent cholecystectomy, suggesting inappropriate ED discharge and highlighting the need for timely follow-up. Early outpatient surgical consultation is critical in determining appropriateness for cholecystectomy and avoiding emergent cholecystectomy in older patients with symptomatic gallstones. PMID- 26837283 TI - The clinical potential of Affibody-based inhibitors of C5 for therapeutic complement disruption. PMID- 26837282 TI - Stoichiometric control of live cell mixing to enable fluidically-encoded co culture models in perfused microbioreactor arrays. AB - In vivo, tissues are maintained and repaired through interactions between the present (different) cell types, which communicate with each other through both the secretion of paracrine factors and direct cell-cell contacts. In order to investigate and better understand this dynamic, complex interplay among diverse cell populations, we must develop new in vitro co-culture strategies that enable us to recapitulate such native tissue complexity. In this work, a microfluidic mixer based on a staggered herringbone design was computationally designed and experimentally validated that features the ability to mix large, non-diffusive particles (i.e. live cells) in a programmed manner. This is the first time that the herringbone mixer concept has been shown to effectively mix particles of the size range applicable to live cells. The cell mixer allowed for sequentially mixing of two cell types to generate reverse linear concentration co-culture patterns. Once validated, the mixer was integrated into a perfused microbioreactor array as an upstream module to deliver mixed cells to five downstream culture units, each consisting of ten serially-connected circular microculture chambers. This novel cell mixer microbioreactor array (CM-MBA) platform was validated through the establishment of spatio-temporally tunable osteogenic co-culture models, investigating the role of pre-osteoblastic cells (SAOS2) on human mesenchymal stem cells (hMSCs) commitment to an osteogenic endpoint. An increase on expression of alkaline phosphatase in sequential (downstream) chambers, consistent with the initial linear distribution of SAOS2, suggests not only osteoblastic cell-driven hMSCs induction towards the osteogenic phenotype, but also the importance of paracrine signaling. In conclusion, the cell mixer microbioreactor array combines the ability to rapidly establish cell co-culture models in a high-throughput, programmable fashion, with the additional advantage of maintaining cells in culture under perfused medium to explore paracrine factor impacts, representing a promising new tool for directing multi cellular tissue formation for tissue engineering applications. PMID- 26837284 TI - An evaluation of a teaching strategy: The use of literature when teaching pre registration midwifery students on pregnancy and loss. AB - Facilitating emotional intelligence and insight in midwifery can be challenging, and the purpose of this paper is to illustrate how this can be nurtured through the use of poetry, in particular Seamus Heaney's poem Elegy for a Still Born Child. Students' ability to gain insight into the experience of bereaved parents and achieve an emotional grasp of the situation through vicarious experience were evaluated. Qualitative data from evaluations was content analysed and significant themes emerged. Students' comments clearly support the suggestion that use of this poem has enhanced emotional intelligence. The data also indicates that vicarious experience gained through reading this poem has helped to nurture sensitivity and professional insight into the impact of still birth on a father. PMID- 26837285 TI - Significant enhancement of magnetoresistance with the reduction of particle size in nanometer scale. AB - The Physics of materials with large magnetoresistance (MR), defined as the percentage change of electrical resistance with the application of external magnetic field, has been an active field of research for quite some times. In addition to the fundamental interest, large MR has widespread application that includes the field of magnetic field sensor technology. New materials with large MR is interesting. However it is more appealing to vast scientific community if a method describe to achieve many fold enhancement of MR of already known materials. Our study on several manganite samples [La(1-x)Ca(x)MnO3 (x = 0.52, 0.54, 0.55)] illustrates the method of significant enhancement of MR with the reduction of the particle size in nanometer scale. Our experimentally observed results are explained by considering model consisted of a charge ordered antiferromagnetic core and a shell having short range ferromagnetic correlation between the uncompensated surface spins in nanoscale regime. The ferromagnetic fractions obtained theoretically in the nanoparticles has been shown to be in the good agreement with the experimental results. The method of several orders of magnitude improvement of the magnetoresistive property will have enormous potential for magnetic field sensor technology. PMID- 26837286 TI - Regulating wave front dynamics from the strongly discrete to the continuum limit in magnetically driven colloidal systems. AB - The emergence of wave fronts in dissipative driven systems is a fascinating phenomenon which can be found in a broad range of physical and biological disciplines. Here we report the direct experimental observation of discrete fronts propagating along chains of paramagnetic colloidal particles, the latter propelled above a traveling wave potential generated by a structured magnetic substrate. We develop a rigorously reduced theoretical framework and describe the dynamics of the system in terms of a generalized one-dimensional dissipative Frenkel-Kontorova model. The front dynamics is explored in a wide range of field parameters close to and far from depinning, where the discrete and continuum limits apply. We show how symmetry breaking and finite size of chains are used to control the direction of front propagation, a universal feature relevant to different systems and important for real applications. PMID- 26837287 TI - Clinical Approach to Diagnosis and Management of Cancer of the Cervix and Vulva. AB - This content presents pathology of the cervix and vulva - its diagnosis, staging, treatment, and prognosis. The authors distinguish between the clinical staging of cervical cancer and the surgical staging of vulvar cancer and note advances in surgical, medical, and radiation oncology in the treatment of both cervical and vulvar carcinoma that allow for individualization of patient treatment resulting in improved oncologic outcomes and improved quality of life. Treatment algorithms are presented based on the varying stages at which the cancer is diagnosed. PMID- 26837288 TI - Neoplastic Lesions of the Cervix. AB - This review presents a discussion of the gross and microscopic features, diagnosis, differential diagnosis, and prognosis of neoplastic lesions of the cervix. Biomarkers are discussed for each entity presented - cervical intraepithelial neoplasia, squamous carcinoma, glandular neoplasms, adenocarcinoma in situ, adenosquamous carcinoma, and others. PMID- 26837289 TI - Pathology of Vulvar Neoplasms. AB - Carcinoma of the vulva is an uncommon malignant neoplasm (approximately one-fifth as frequent as cervical cancer) and represents 4% of all genital cancers in women. Approximately two-thirds of cases occur in women older than 60 years, and squamous cell carcinoma is the most common histologic type. Several different subtypes of squamous cell carcinoma have been described in the vulva; however, in terms of etiology, pathogenesis, and histologic features, most carcinomas belong to one of two categories: keratinizing squamous cell carcinomas associated with chronic inflammatory skin disorders, and basaloid or warty carcinomas related to infection with high oncogenic risk human papillomaviruses. Glandular neoplasms of the vulva arise from the vulvar apocrine sweat glands (papillary hidradenoma and Paget disease) or the Bartholin gland and their cause is not known. PMID- 26837290 TI - Clinical Approach to Diagnosis and Management of Endometrial Hyperplasia and Carcinoma. AB - This article focuses on the most important neoplastic epithelial lesions of the uterus, endometrial hyperplasia and carcinoma. The primary management of hyperplastic lesions and carcinoma is often surgical but nonsurgical options are possible for both, depending on specific patients and tumor characteristics. Many controversies still exist regarding the optimal medical and surgical treatments of hyperplasias and carcinomas of the endometrium. There is a need to more accurately select patients for lymph node sampling or dissection. The role of adjuvant therapies for endometrial carcinomas is still under investigation. This review covers current understanding in the diagnosis and clinical management of endometrial hyperplasias and carcinomas. PMID- 26837291 TI - Selected Topics in the Molecular Pathology of Endometrial Carcinoma. AB - In the developed world, endometrial carcinoma is the most common malignant tumor of the female gynecologic tract. Numerous epidemiologic studies indicate that exposure to unopposed estrogen is a significant risk factor for developing endometrial cancer, particularly endometrioid-type endometrial carcinoma; however, a number of other molecular pathways and mechanisms are also important in endometrial cancer. In this review, the authors highlight some of the more interesting molecular pathways in endometrial cancer, such as the PTEN/PI3K/AKT pathway, microsatellite instability, and molecular mediators of epithelial-to mesenchymal transition. PMID- 26837292 TI - Atypical Endometrial Hyperplasia and Well Differentiated Endometrioid Adenocarcinoma of the Uterine Corpus. AB - The distinction between atypical endometrial hyperplasia and well differentiated adenocarcinoma of the endometrium is one of the more difficult differential diagnoses in gynecologic pathology. Different pathologists apply different histologic criteria, often with different individual thresholds for atypical endometrial hyperplasia and grade 1 adenocarcinoma. While some classifications are based on a series of molecular genetic alterations (which may or may not translate into biologically or clinically relevant risk lesions), almost all current diagnostic criteria use a series of histologic features - usually a combination of architecture and cytology - for diagnosing atypical hyperplasia and adenocarcinoma. This article presents evidence-based histologic criteria for atypical endometrial hyperplasia and low grade endometrial carcinoma (both FIGO grade 1 and 2) with emphasis on common and not so common histologic mimics. Grade 3 endometrioid carcinoma is discussed in the Oliva and Soslow article in this publication. PMID- 26837293 TI - High-Grade Endometrial Carcinomas. AB - High-grade endometrial carcinomas are a heterogeneous group of clinically aggressive tumors. They include FIGO grade 3 endometrioid carcinoma, serous carcinoma, clear cell carcinoma, undifferentiated carcinoma, and malignant mixed Mullerian tumor (MMMT). Epidemiologic, genetic, biologic prognostic and morphologic differences between these entities are striking in prototypic cases, yet substantial overlap exists and diagnostic criteria and therapeutic approaches that account for the group's diversity are currently insufficient. FIGO grade 3 endometrioid carcinoma demonstrates solid, trabecular or nested growth and may resemble poorly differentiated squamous cell carcinoma. Endometrioid glandular differentiation is usually focally present. Serous carcinoma usually displays papillary architecture but glandular and solid patterns may predominate. Tumor cells typically display diffuse and severe atypia. Clear cell carcinoma should be diagnosed by recognizing characteristic papillary or tubulocystic architecture with cuboidal tumor cells showing atypical but uniform nuclei. Cells with clear cytoplasm are frequently but not always present. On the other hand, clear cells may be encountered in endometrioid and serous carcinomas. Immunohistochemical stains for p53, p16, ER, PR, mib-1, hepatocyte nuclear factor 1beta and pan cytokeratin can be helpful in classifying these high-grade carcinomas. They should be used in concert with thorough morphologic examination, as part of a rational panel of markers and only in specific circumstances. Although these tumors may appear clinically and even morphologically similar, demographic and epidemiologic features as well as patterns of spread and treatment modalities differ. PMID- 26837294 TI - Familial Tumors of the Uterine Corpus. AB - Women with Lynch syndrome are at considerable risk for developing endometrial carcinoma, but current screening guidelines for detection of Lynch syndrome focus almost exclusively on colorectal carcinoma. Lynch syndrome associated colorectal and endometrial carcinomas have some important differences with implications for screening strategies. These differences are discussed in this review, along with the most effective screening criteria and testing methods for detection of Lynch syndrome in endometrial carcinoma patients. PMID- 26837295 TI - Clinical Approach to Diagnosis and Management of Ovarian, Fallopian Tube, and Peritoneal Carcinoma. AB - Ovarian, fallopian tube and peritoneal carcinomas make up the deadliest group of malignancies of the female genital tract. Ovarian carcinoma is the second most common malignancy of the female reproductive tract in developed countries and the sixth most common cancer diagnosed in women in the United States. While signs and symptoms of ovarian carcinoma related to the mass-effect of advanced disease are relatively common, no reliable signs or symptoms are seen in patients with early ovarian carcinoma. The diagnosis can only be made by surgical removal and pathologic evaluation of a suspicious mass. The authors present an overview of the disease and discussions of genetic predisposition, prevention, screening, and diagnosis of ovarian, fallopian tube and primary peritoneal carcinomas. Details on staging procedures as well as surgical and chemotherapeutic techniques are outlined for the various stages of disease. PMID- 26837296 TI - Molecular Pathology of Ovarian Carcinomas. AB - This content presents a review of molecular pathology of ovarian cancer. The authors present key molecular features for high-grade and low-grade serous carcinomas, endometrioid carcinomas, clear cell carcinomas, and mucinous carcinomas. Cell lineage, mutation and gene expression, pathway alterations, risk factors, prognostic markers, and treatment targets are discussed. PMID- 26837297 TI - Metastatic Neoplasms Involving the Ovary. AB - In this review, ovarian metastatic carcinomas from various sites, as well as other neoplasms secondarily involving the ovary, are discussed. As well as describing the morphology, the value of immunohistochemistry in distinguishing between primary and metastatic neoplasms in the ovary is discussed. While immunohistochemistry has a valuable role to play and is paramount in some cases, the results should be interpreted with caution and with regard to the clinical picture and gross and microscopic pathologic findings. PMID- 26837298 TI - Benign and Low Grade Serous Epithelial Tumors: Recent Developments and Diagnostic Problems. AB - This review focuses on recent advances in the area of low-grade ovarian serous neoplasia with emphasis on key diagnostic criteria, differential diagnosis, and disease classification based on current understanding of low-grade serous carcinogenesis. Despite considerable controversy surrounding serous tumors of low malignant potential (S-LMP) or borderline tumors, there have been great strides in our understanding of the serous group of borderline and malignant pelvic epithelial neoplasms in the past decade. Most S-LMP have a favorable prognosis, but recurrences and progression to carcinoma occur, sometimes following a protracted clinical course. Pathologic risk factors vary, but the extraovarian implant status is the most important predictor for progressive disease. Progression of S-LMP usually takes the form of low-grade serous carcinoma, although transformation to high-grade carcinoma is occasionally seen. A pelvic S LMP - low-grade serous carcinoma pathway has been proposed based on global gene expression profiling, shared mutations in KRAS and/or BRAF, and in most cases, the presence of S-LMP in de novo low-grade serous carcinoma. Unlike high-grade serous carcinoma, low-grade serous carcinoma responds poorly to standard platinum based chemotherapy. Development of more tailored therapy for S-LMP with invasive implants and low-grade serous carcinoma, ideally based on a relative risk model for disease progression, is under active clinical investigation. PMID- 26837299 TI - High-Grade Serous Carcinoma Involving Fallopian Tube, Ovary and Peritoneum. AB - The focus of this review is high-grade serous carcinoma (HGSC); for the purposes of this review, the term "pelvic SC" is used for HGSC that could be considered, based on historical definitions, to have arisen from ovary, fallopian tube, or peritoneum. These assignments of primary site are arbitrary and there is evidence that the distal fallopian tube is the site of origin of many pelvic HGSCs. The diagnosis of HGSC can be made readily based on routine histomorphologic examination in most cases; however, a variety of neoplasms can resemble HGSC. Thus, we review the key features of pelvic SC, current concepts of its pathogenesis, histopathological diagnostic criteria, discuss differential diagnosis, and review diagnostic ancillary studies that can be used in practice. PMID- 26837300 TI - Nonserous Ovarian Epithelial Tumors. AB - This review covers the group of relatively uncommon nonserous ovarian epithelial tumors. The authors focus on the group's distinctiveness from the much more common serous tumors and show the similarities across entities. Diagnostic criteria that separate the different entities are currently being debated. Particular problems include the reproducible diagnosis of high-grade endometrioid, transitional cell, mixed epithelial and undifferentiated carcinomas. Furthermore, despite recognition that most malignant mucinous tumors involving ovary represent metastases from extraovarian primary sites, many misdiagnoses still occur. The authors discuss their rationale behind their opinions about these problematic topics. PMID- 26837301 TI - Hereditary Carcinomas of the Ovary, Fallopian Tube, and Peritoneum. AB - Approximately 10% of ovarian cancers are associated with inherited germline mutations, most commonly of the BRCA1 or BRCA2 genes. The majority of BRCA1 and BRCA2 cancers are high-grade serous carcinomas diagnosed at an advanced stage, and there are as yet no histologic features that distinguish these tumors from sporadic serous cancers. Many women identified as being at high genetic risk undergo prophylactic salpingo-oophorectomy, and careful histopathological examination of these specimens may identify occult carcinoma, frequently in the distal fallopian tube. In addition, serous cancer precursors, including tubal intraepithelial carcinoma, have been increasingly recognized in distal and fimbrial epithelium. Little has been documented to date of the histopathological features of the cancers associated with the hereditary nonpolyposis colon cancer syndrome, but it appears these ovarian cancers may include a variety of histologic types, and in contrast to the BRCA cancers, are low grade and early stage. PMID- 26837302 TI - Gynecologic Pathologists: Physicians at the Crossroads of Diagnosis and Clinical Care. PMID- 26837303 TI - Estimating the magnitude of female genital mutilation/cutting in Norway: an extrapolation model. AB - BACKGROUND: With emphasis on policy implications, the main objective of this study was to estimate the numbers of two main groups affected by FGM/C in Norway: 1) those already subjected to FGM/C and therefore potentially in need for health care and 2) those at risk of FGM/C and consequently the target of preventive and protective measures. Special attention has been paid to type III as it is associated with more severe complications. METHODS: Register data from Statistics Norway (SSB) was combined with population-based survey data on FGM/C in the women/girls' countries of origin. RESULTS: As of January 1(st) 2013, there were 44,467 first and second-generation female immigrants residing in Norway whose country of origin is one of the 29 countries where FGM/C is well documented. About 40 pct. of these women and girls are estimated to have already been subjected to FGM/C prior to immigration to Norway. Type III is estimated in around 50 pct. of those already subjected to FGM/C. Further, a total of 15,500 girls are identified as potentially at risk, out of which an approximate number of girls ranging between 3000 and 7900 are estimated to be at risk of FGM/C. CONCLUSION: Reliable estimates on FGM/C are important for evidence-based policies. The study findings indicate that about 17,300 women and girls in Norway can be in need of health care, in particular the 9100 who are estimated to have type III. Preventive and protective measures are also needed to protect girls at risk (3000 to 7900) from being subjected to FGM/C. Nevertheless, as there are no appropriate tools at the moment that can single these girls out of all who are potentially at risk, all girls in the potentially at risk group (15,500) should be targeted with preventive measures. PMID- 26837304 TI - Fall-related gait characteristics on the treadmill and in daily life. AB - BACKGROUND: Body-worn sensors allow assessment of gait characteristics that are predictive of fall risk, both when measured during treadmill walking and in daily life. The present study aimed to assess differences as well as associations between fall-related gait characteristics measured on a treadmill and in daily life. METHODS: In a cross-sectional study, trunk accelerations of 18 older adults (72.3 +/- 4.5 years) were recorded during walking on a treadmill (Dynaport Hybrid sensor) and during daily life (Dynaport MoveMonitor). A comprehensive set of 32 fall-risk-related gait characteristics was estimated and compared between both settings. RESULTS: For 25 gait characteristics, a systematic difference between treadmill and daily-life measurements was found. Gait was more variable, less symmetric, and less stable during daily life. Fourteen characteristics showed a significant correlation between treadmill and daily-life measurements, including stride time and regularity (0.48 < r < 0.73; p < 0.022). No correlation between treadmill and daily-life measurements was found for stride-time variability, acceleration range and sample entropy in vertical and mediolateral direction, gait symmetry in vertical direction, and stability estimated as the local divergence exponent by Rosenstein's method in mediolateral direction (r < 0.16; p > 0.25). CONCLUSIONS: Gait characteristics revealed less stable, less symmetric, and more variable gait during daily life than on a treadmill, yet about half of the characteristics were significantly correlated between conditions. These results suggest that daily-life gait analysis is sensitive to static personal factors (i.e., physical and cognitive capacity) as well as dynamic situational factors (i.e., behavior and environment), which may both represent determinants of fall risk. PMID- 26837305 TI - Malignant paraganglioma in children treated with embolization prior to surgical excision. AB - BACKGROUND: Paragangliomas (PGL) are rare tumors derived from neural crest cells, whose origins may vary along the chain of the sympathetic nervous system. Such tumors are often characterized by secretion of catecholamines, but sometimes they are biochemically inactive, which makes diagnosis often challenging. Malignant paraganglioma is defined by the presence of this tumor at sites where chromaffin cells are usually not found or by local invasion of the primary tumor. Recurrence, either regional or metastatic, usually occurs within 5 years of the initial complete resection but long-term recurrence is also described. Malignancy is often linked to a SDHB mutation. Preoperative embolization has been applied in the surgical management of PGLs with the objective to decrease intra-operative blood loss and surgery length without complications. CASE PRESENTATION: We report two cases of patients with abdominal or pelvic malignant PGLs who have been treated surgically at our center after preoperative embolization. Surgery was a very challenging procedure with multiple surgical teams involved and embolization did not prevent major blood loss and intraoperative complications. Patients required adjuvant treatment with either chemotherapy or radiotherapy. CONCLUSIONS: Many studies in the adult population have established recommendations for the diagnosis and therapeutic management of PGL, but few studies concern the pediatric population. Because malignant PGL is more important in the pediatric population, screening and early diagnosis of PGL is advisable in children with genetic predisposing. Surgical resection is the mainstay of treatment, but a multimodal approach is often required due to the complexity of cases. The role of preoperative embolization is not established and in our experience it has provided little benefit and major complications. PMID- 26837306 TI - Compression of the peroneal nerve by a neurofibroma originating from collaterals of the peroneal nerve: a case report. AB - BACKGROUND: Paralysis of the external popliteal sciatic nerve is a frequent pathological condition that occurs after trauma. However, etiologies other than trauma, such as tumors, are also possible. The sensory collaterals of the external popliteal sciatic nerve have a small territory of innervation at the knee, and tumors involving these nerves become symptomatic after compression of the motor nerves. We here describe the first reported case of this phenomenon. CASE PRESENTATION: This case involved a lesion compressing the origin of the external popliteal sciatic nerve of a 13-year-old Moroccan boy diagnosed with a neurofibroma. He developed functional impairment of his left lower limb during a football game, and examination revealed a steppage gait. The initial diagnosis was stretching of the peroneal nerve. The definitive diagnosis of a neurofibroma was revealed by imaging and confirmed by surgery and pathology. Treatment involved total removal of the tumor; however, our patient's steppage gait persisted. CONCLUSIONS: Our patient developed compression of the external popliteal sciatic nerve from a tumor growing on a collateral nerve. Early diagnosis is an absolute necessity in such cases. Trauma and tumors of sensory nerves can distort the diagnosis, as in this case. Ultrasound and magnetic resonance imaging can contribute to an accurate diagnosis in patients with neuropathy in the absence trauma or tomacula. PMID- 26837309 TI - Routinely collected English birth data sets: comparisons and recommendations for reproductive epidemiology. AB - BACKGROUND: In England there are four national routinely collected data sets on births: Office for National Statistics (ONS) births based on birth registrations; Hospital Episode Statistics (HES) deliveries (mothers' information); HES births (babies' information); and NHS Numbers for Babies (NN4B) based on ONS births plus gestational age and ethnicity information. This study describes and compares these data, with the aim of recommending the most appropriate data set(s) for use in epidemiological research and surveillance. METHODS: We assessed the completeness and quality of the data sets in relation to use in epidemiological research and surveillance and produced detailed descriptive statistics on common reproductive outcomes for each data set including temporal and spatial trends. RESULTS: ONS births is a high quality complete data set but lacks interpretive and clinical information. HES deliveries showed good agreement with ONS births but HES births showed larger amounts of missing or unavailable data. Both HES data sets had improved quality from 2003 onwards, but showed some local spatial variability. NN4B showed excellent agreement with ONS and HES deliveries for the years available (2006-2010). Annual number of births increased by 17.6% comparing 2002 with 2010 (ONS births). Approximately 6% of births were of low birth weight (2.6% term low birth weight) and 0.5% were stillbirths. CONCLUSIONS: Routinely collected data on births provide a valuable resource for researchers. ONS and NN4B offer the most complete and accurate record of births. Where more detailed clinical information is required, HES deliveries offers a high quality data set that captures the majority of English births. PMID- 26837311 TI - Effect of surgical ligation of the patent ductus arteriosus on cerebral perfusion of premature infants in the postoperative period. PMID- 26837310 TI - Delivery room management of extremely preterm infants: the EPIPAGE-2 study. AB - OBJECTIVE: To analyse the delivery room management of babies born between 22 and 26 weeks of completed gestational age and to identify the factors associated with the withholding or withdrawal of intensive care. STUDY DESIGN: Population-based cohort study. PATIENTS AND METHODS: Our study population comprised 2145 births between 22 and 26 completed weeks enrolled in the EPIPAGE-2 study, a French cohort of very preterm infants born in 2011. The primary outcome measure was withholding or withdrawal of intensive care in the delivery room. RESULTS: Among infants born alive at 22-23 weeks, intensive care was withheld or withdrawn for >90%. At 24 weeks, resuscitative measures were withheld or withdrawn for 38%, at 25 weeks for 8% and at 26 weeks for 3%. Other factors besides gestational age at birth associated with this withholding or withdrawal for infants born at 24-26 weeks were birth weight <600 g, emergency delivery (within 24 h of the mother's admission) and singleton pregnancy. Although rates of withholding or withdrawal of intensive care varied substantially between maternity units (from 0% to 100%), the variability was primarily explained by differences in distributions of gestational age at birth. CONCLUSIONS: Although gestational age is only one factor predicting survival of preterm infants, practices in France appear to be based primarily on this factor, which thus has direct effects on the survival of extremely preterm infants. The ethical implications of basing life and death decisions only on gestational age before 25 weeks require further examination. PMID- 26837312 TI - BCR-ABL1 expression, RT-qPCR and treatment decisions in chronic myeloid leukaemia. AB - AIMS: RT-qPCR is used to quantify minimal residual disease (MRD) in chronic myeloid leukaemia (CML) in order to make decisions on treatment, but its results depend on the level of BCR-ABL1 expression as well as leukaemic cell number. The aims of the study were to quantify inter-individual differences in expression level, to determine the relationship between expression level and response to treatment, and to investigate the effect of expression level on interpretation of the RT-qPCR result. METHODS: BCR-ABL1 expression was studied in 248 samples from 65 patients with CML by determining the difference between MRD quantified by RT qPCR and DNA-qPCR. The results were analysed statistically and by simple indicative modelling. RESULTS: Inter-individual levels of expression approximated a normal distribution with an SD of 0.36 log. Expression at diagnosis correlated with expression during treatment. Response to treatment, as measured by the number of leukaemic cells after 3, 6 or 12 months of treatment, was not related to the level of expression. Indicative modelling suggested that interpretation of RT-qPCR results in relation to treatment guidelines could be affected by variation in expression when MRD was around 10% at 3 months and by both expression variation and Poisson variation when MRD was around or below the limit of detection of RT-qPCR. CONCLUSIONS: Variation between individuals in expression of BCR-ABL1 can materially affect interpretation of the RT-qPCR when this test is used to make decisions on treatment. PMID- 26837313 TI - Mannose-binding lectin deficiency and predisposition to recurrent infection in adults. AB - AIMS: The effects of mannose-binding lectin (MBL) deficiency are well known in children and in those with a compromised immune system. However, its effects in adults are debateable, with little research having been carried out in the UK regarding infection risk in otherwise healthy adults with an MBL deficiency. METHODS: Using an ELISA, we investigated the prevalence of MBL deficiency in both healthy adults and those with recurrent infection. The aim was to determine first if there was a disparity in MBL levels between the two groups and second to investigate the effect of severe deficiency. RESULTS: Overall, the difference between the two groups for MBL level was found not to be statistically significant (p=0.203); however, there was a higher prevalence of severe deficiency (MBL<75 ng/mL) in the patients with recurrent infection (p=0.03). CONCLUSIONS: It was concluded that there is justified reason for continuing to perform the MBL test in adult patients suffering recurrent infection. PMID- 26837314 TI - Computer-based-limited and personalised education management maximise appropriateness of vitamin D, vitamin B12 and folate retesting. AB - AIM: To identify the best management strategy for improving the appropriateness of vitamin D, vitamin B12 and folate retesting. METHODS: The study was conducted between 3 November 2012 and 8 June 2015, with inpatients and outpatients being considered separately. After an observational reference period (3 November 2012 to 14 September 2013), an information technology (IT)-based permissive strategy (16 September 2013 to 27 July 2014) followed by a limiting strategy was used to manage the demand for inpatient retesting. For outpatients, an educational strategy period (28 July 2014 to 16 December 2014) with direct contact between medical personnel and general practitioners (GPs) was followed by a post educational period without any restriction. Data from a total of 66 496 patients for vitamin D, 14 618 for vitamin B12 and 14 445 for folate were retrieved from the laboratory IT system. The main outcomes measures were inappropriate vitamin D, vitamin B12 and folate retesting. The minimal retesting intervals were 90 (vitamin D) or 180 days (vitamin B12 and folate). RESULTS: In the absence of a laboratory demand strategy, the frequency of inappropriate retesting for vitamin D, vitamin B12 and folate was 60%, 94% and 93%, respectively, for inpatients, and 27%, 87% and 87%, respectively, for outpatients. A limiting IT-based demand management strategy reduced inappropriate retesting for vitamin D (36%), but not for vitamin B12 and folate. The educational strategy was followed by a reduction in inappropriate retesting among outpatients (16% for vitamin D, 72% for vitamin B12 and folate). CONCLUSIONS: Laboratory demand management based on an IT limiting management strategy or on education of the referring physicians appears helpful in maximising appropriate retesting. PMID- 26837316 TI - Psychological health and HIV transmission among female sex workers: a systematic review and meta-analysis. AB - Current HIV prevention interventions for female sex workers (FSWs) have tended to target the cognitive factors in changing their behaviors, yet little attention has been paid to the psychological factors that influence the behavior of women in sex work. This review aimed to explore the associations between the psychological health of FSWs and HIV risk. A total of eight studies published in English before July 2013 were identified and reviewed. FSWs had reported psychological issues, including depression, suicidal thoughts as well as lower quality of life, and the pooled prevalence of probable depression was as high as 62.4%. The majority of studies showed that higher scores in psychological health problems were associated with increased HIV risk behavior, in particular inconsistent condom use, or sexually transmitted infections. Among the five studies which measured symptoms of depression, four documented that higher depression scores were significantly associated with inconsistent condom use among FSWs with their clients and/or partners. Meta-analysis using a fixed effects model was performed to examine the association between depression and inconsistent condom use and found that higher scores in depression were significantly associated with inconsistent condom use (odds ratio = 2.57, p < .001). This review contends that future HIV preventive interventions should take psychological health of FSWs into consideration. PMID- 26837315 TI - miR-320a mediates doxorubicin-induced cardiotoxicity by targeting VEGF signal pathway. AB - BACKGROUND: Vascular homeostasis abnormalities may involve in doxorubicin induced cardiotoxicity. METHODS: Enhanced cardiac miR-320a expression, reduced cardiac microvessel density and impaired cardiac function were observed in mice treated by anthracycline doxorubicin. To further explore the role of miR-320a in doxorubicin induced cardiotoxicity, microRNA mimics/inhibitor in vitro and rAAV administration in vivo were employed in mice. RESULTS: Knockdown of miR-320a not only resulted in enhanced proliferation and inhibited apoptosis in cultured endothelial cells, but also attenuated cardiac abnormalities induced by doxorubicin. On the contrary, overexpression of miR-320a enhanced apoptosis in vitro, and aggravated vessel abnormalities in heart and subsequent cardiac dysfunction in mice. Furthermore, Western blot assays showed that VEGF-A was a potential target of miR-320a, which was verified by anti-Ago2 co immunoprecipitation. Moreover, as same as miR-320a, siRNA against VEGF-A reinforced doxorubicin induced endothelial cells injury. Finally, the negative effects of miR-320a on vascular homeostasis and cardiac function were alleviated by VEGF-A re-expression in doxorubicin treated mice. CONCLUSION: Our observations demonstrate that miR-320a play important roles in doxorubicin induced cardiotoxicity via vessel homeostasis in heart and thus, inhibition of miR-320a may be applied to the treatment of cardiac dysfunction induced by anthracycline. PMID- 26837317 TI - An Assessment of Collaboration and Disasters: A Hospital Perspective. AB - INTRODUCTION: There is no standard guidance for strategies for hospitals to use to coordinate with other agencies during a disaster. HYPOTHESIS/PROBLEM: This study analyzes successful strategies and barriers encountered by hospitals across the nation in coordinating and collaborating with other response agencies. METHODS: Quantitative and qualitative data were collected from a web-based study from 577 acute care hospitals sampled from the 2013 American Hospital Association (AHA) database. The results were analyzed using descriptive statistics. RESULTS: The most common barriers to collaboration are related to finances, ability to communicate, and personnel. PMID- 26837318 TI - The importance of measuring customer satisfaction in palliative care. AB - In the last decades, palliative care has been more and more focused on the evaluation of patients' and families' satisfaction with care. However, the evaluation of customer satisfaction in palliative care presents a number of issues such as the presence of both patients and their families, the frail condition of the patients and the complexity of their needs, and the lack of standard quality indicators and appropriate measurement tools. In this manuscript, we critically review existing evidence and literature on the evaluation of satisfaction in the palliative care context. Moreover, we provide - as a practical example - the preliminary results of our experience in this setting with the development of a dedicated tool for the measurement of satisfaction. PMID- 26837319 TI - [CME: Lymphoproliferative diseases after transplantation (PTLD)]. PMID- 26837321 TI - [Wound Ballistics - a Brief Overview]. AB - Wound ballistics examines the specific effect, namely the wound profile, of bullets on the body by firing at synthetic models made of ordnance gelatine, glycerin soap and synthetic bones, validated with real cases from (battlefield) surgery and forensic pathology. Wound profile refers to the penetration depth, the bullet deformation/ fragmentation, the diameter of the permanent and the temporary wound cavity. Knowing these features and the used ammunition a surgeon can rapidly assess the amount damage within a patient. The forensic pathologist can draw conclusions as to the used ammunition based on the wound profile. By measuring of the destructive capability of different ammunition types, wound ballistics lays the foundation for guidelines concerning the maximum effect of military ammunition. PMID- 26837322 TI - [Radiology Update Ultrasound Elastography - Quintessence for the Primary Care Physician]. AB - Ultrasound elastography visualizes and measures elasticity of tissue. Depending on the methods there are four types of elastography: strain elastography (SE), transient elastography (TE), acoustic radiation force impulse imaging (ARFI) and shear wave elastography (SWE). Due to the fact that pathological changes in the tissue in most of the cases mean a lower elasticity, ultrasound elastography is able to diagnose diseases such as liver fibrosis, liver cirrhosis, to help in the diagnosis of suspicious lesions in mamma, prostate and thyroid gland. So far, ultrasound elastography is not yet able to replace other standardized diagnostic tools but can add valuable diagnostic information. PMID- 26837323 TI - [Male Breast Cancer: What is Different?]. AB - Male breast cancer is a rare disease. Symptoms and signs resemble breast cancer in women: A palpable mass, enlarged lymph nodes or skin changes (ulceration, secretion, peau d'orange) mandate mammography, ultrasound to assess the regional lymph nodes. The definitive diagnosis is made by biopsy. Men with breast cancer are treated along the same principles as women: resection followed by systemic and radiation therapy. Tamoxifen, not aromatase inhibitors, is the adjuvant therapy of choice for estrogen receptor positive tumors. Therapy of men with metastatic breast cancer follows the same principles as therapy of women. PMID- 26837324 TI - [How to Manage Chronic Diarrhoea]. AB - The differential diagnosis of chronic diarrhoea is broad and the evaluation of these patients represents a diagnostic challenge. This review provides a practical approach to reduce unnecessary testing while minimising the oversight of an important disease. Initial investigations include a detailed history, physical examination, and basic laboratory tests. Most younger patients (<50) with normal initial screen have functional diarrhoea. In patients above age 50, colonoscopy is recommended complementary for initial evaluation. In the absence of an identifiable cause, categorizing patients by having inflammatory or non inflammatory chronic diarrhoea is helpful in directing further evaluation. PMID- 26837325 TI - [The Throwing Shoulder]. AB - Repetitive top-performance of overhead athletes induces a tremendous stress for the throwing shoulder. Throwers reach rotational speed of their arm of more than 7000 degrees /s with joint compression and distraction forces of more than 1000 N. This performance is tributary to adaption of the shoulder muscles and the joint itself. These adaptions may, however lead to two specific problems of the throwing shoulder: 1. The posterosuperior internal impingement of the rotator cuff and labrum between glenoid and humeral head during late cooking phase; 2. A decreased internal rotation of the glenohumeral joint (GIRD) with compensatory problems of the scapula-stabilizing muscles. Precise analysis of kinematics and pathomechanics aims to improve understanding and treatment of those specific problems of the throwing shoulder. PMID- 26837326 TI - [COPD: LAMA / LABA fixed combination more effective than separately ]. PMID- 26837327 TI - [Which intervention is most appropriate to reverse the development of frailty in the elderly?]. PMID- 26837329 TI - [CME-Rheumatology 7: Trochanter major pain syndrome]. PMID- 26837331 TI - CagA promotes proliferation and secretion of extracellular matrix by inhibiting signaling pathway of apoptosis in rat glomerular mesangial cells. AB - Cytotoxin-associated antigen A (CagA), a major virulence factor of Helicobacter pylori (Hp), is associated with the pathogenesis of peptic ulcer and gastric cancer. Recent researches demonstrated that Hp exists in palatine tonsil in all studied IgA nephropathy (IgAN) patients, most of which were CagA-positive, suggesting that CagA may be a causative pathogenic factor of IgAN. However, the underlying molecular mechanisms and signaling pathway are still largely unclear. In the present study, CCK8 assay, enzyme-linked immunosorbent assay, and immunohistochemistry were performed to investigate the effect of CagA on cell proliferation and extracellular matrix secretion in rat glomerular mesangial cells. RT-PCR and western blotting were used to reveal the potential signaling pathway. Rat glomerular mesangial cells were treated with recombinant CagA protein for 72 h, in a dose- and time-dependent manner. We found that CagA promoted cell proliferation and extracellular matrix secretion by inhibiting signaling pathway of apoptosis. Taken together, these findings suggested that CagA induced cellular injury in glomerular mesangium by proliferation and secretion of extracellular matrix, and may play an important role in pathogenesis of IgAN. PMID- 26837333 TI - Improving HPV Vaccination Coverage Rates in Rhode Island. PMID- 26837334 TI - In vivo medical imaging technologies: new possibility in diagnosis of gastric cancer. AB - Gastric cancer is one of the most common cancers with an important related mortality worldwide. It is preceded by a multistage pathological state arising from environmental and dietary factors. These factors influence intracellular molecular changes associated with the gastric carcinogenesis. Gastroenterology imaging, such as endoscopy, is essential for an early diagnosis as patients are typically asymptomatic at the onset of gastric cancer. Recent technological advances have allowed the development of novel imaging devices such as narrow band imaging or high-definition endoscopy. Their accuracy in determining early gastric lesions makes biopsy of tissue unnecessary. They may largely simplify early diagnosis and improved prognosis. We performed a qualitative review about endoscopic application of advanced imaging technologies. PMID- 26837332 TI - Neurocognitive and psychiatric dimensions of hot, but not cool, impulsivity predict HIV sexual risk behaviors among drug users in protracted abstinence. AB - BACKGROUND: Impulsivity is an important risk factor for HIV risky drug and sexual behaviors. Research identifies hot (i.e. affectively-mediated, reward-based) and cool (motoric, attentional, independent of context) neurocognitive and psychiatric dimensions of impulsivity, though the impact of specific drugs of abuse on these varieties of impulsivity remains an open question. OBJECTIVES: The present study examined the associations of neurocognitive and psychiatric varieties of hot and cool impulsivity with measures of lifetime and recent sexual risk behaviors among users of different classes of drugs. METHODS: The study sample was comprised of drug users in protracted (> 1 year) abstinence: heroin mono-dependent (n = 61), amphetamine mono-dependent (n = 44), and polysubstance dependent (n = 73). Hot impulsivity was operationalized via neurocognitive tasks of reward-based decision-making and symptoms of psychopathy. Cool impulsivity was operationalized via neurocognitive tasks of response inhibition and symptoms of attention deficit/hyperactivity disorder (ADHD). RESULTS: Hot impulsivity was associated with sexual risk behaviors among heroin and amphetamine users in protracted abstinence, whereas cool impulsivity was not associated with sexual risk behaviors among any drug-using group. Neurocognitive hot impulsivity was associated with recent (past 30-day) sexual risk behaviors, whereas psychopathy was associated with sexual risk behaviors during more remote time-periods (past 6 month and lifetime) and mediated the association between heroin dependence and past 6-month sexual risk behaviors. CONCLUSION: Assessments and interventions aimed at reducing sexual risk behaviors among drug users should focus on hot neurocognitive and psychiatric dimensions of impulsivity, such as decision-making and psychopathy. Cool dimensions of impulsivity such as response inhibition and ADHD were not related to sexual risk behaviors among drug users in protracted abstinence. PMID- 26837335 TI - Early Prediction of Tumor Response to Treatment: Preclinical Validation of 99mTc Duramycin. AB - Noninvasive imaging of cell death can provide an early indication of the efficacy of tumor treatment, aiding clinicians in distinguishing responding patients from nonresponding patients early on. (99m)Tc-duramycin is a SPECT tracer for cell death imaging. In this study, our aim was to validate the use of (99m)Tc duramycin for imaging the early response of tumors to treatment. METHODS: An in vitro binding assay was performed on COLO205 cells treated with 5-fluorouracil (3.1, 31, or 310 MUM) and oxaliplatin (0.7 or 7 MUM) or radiation (2 or 4.5 Gy). (99m)Tc-duramycin cell binding and the levels of cell death were evaluated after treatment. In vivo imaging was performed on 4 groups of CD1-deficient mice bearing COLO205 human colorectal cancer tumors. Each group included 6 tumors. The first group was given irinotecan (100 mg/kg), the second oxaliplatin (5 mg/kg), the third irinotecan (80 mg/kg) plus oxaliplatin (5 mg/kg), and the fourth vehicle (0.9% NaCl and 5% glucose). For radiotherapy studies, COLO205 tumors received 4.5 Gy, 2 fractions of 4.5 Gy in a 24-h interval, pretreatment with an 80 mg/kg dose of irinotecan combined with 2 fractions of 4.5 Gy in a 24-h interval, or no treatment (n = 5-6/group). Therapy response was evaluated by (99m)Tc-duramycin SPECT 24 h after the last dose of therapy. Blocking was used to confirm tracer specificity. Radiotracer uptake in the tumors was validated ex vivo using gamma-counting, cleaved caspase-3, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) histology. RESULTS: Chemotherapy and radiotherapy increased (99m)Tc-duramycin binding to COLO205 cells in a concentration/dose- and time-dependent manner, which correlated well with cell death levels (P < 0.05) as analyzed by annexin V and caspase 3/7 activity. In vivo, (99m)Tc-duramycin uptake in COLO205 xenografts was increased 2.3- and 2.8-fold (P < 0.001) in mice treated with irinotecan and combination therapy, respectively. Blocking with unlabeled duramycin demonstrated specific binding of the radiotracer. After tumor irradiation with 4.5 Gy, (99m)Tc duramycin uptake in tumors increased significantly (1.24 +/- 0.07 vs. 0.57 +/- 0.08 percentage injected dose per gram in the unirradiated tumors; P < 0.001). gamma-counting of radioactivity in the tumors positively correlated with cleaved caspase-3 (r = 0.85, P < 0.001) and TUNEL (r = 0.81, P < 0.001) staining. CONCLUSION: We demonstrated that (99m)Tc-duramycin can be used to image induction of cell death early after chemotherapy and radiotherapy. It holds potential to be translated into clinical use for early assessment of treatment response. PMID- 26837336 TI - Association Between 131I Treatment for Thyroid Cancer and Risk of Receiving Cataract Surgery: A Cohort Study from Taiwan. AB - The risk of cataracts after (131)I therapy for cancer is unknown. The objective of this study was to evaluate the association between (131)I therapy for thyroid cancer and risk of receiving cataract surgery in Taiwan. METHODS: This was a nationwide population-based cohort study of patients with thyroid cancer diagnosed during the period 1998-2008. The data were obtained from the Taiwan National Health Insurance Research dataset. The cumulative (131)I activity in each patient was calculated. Hazard ratios were calculated using a time-dependent survival analysis to estimate the effect of (131)I therapy on the risk of receiving cataract surgery. RESULTS: A total of 8,221 patients were eligible for the final analysis (mean age, 43.2 y; mean follow-up, 5.9 y); 69% received (131)I with a median cumulative activity of 3.7 GBq. Two hundred patients received cataract surgery. The adjusted hazard ratios were 0.77 (95% confidence interval, 0.54-1.09), 0.92 (95% CI, 0.64-1.31), and 1.06 (95% CI, 0.58-1.94) for cumulative (131)I activities of 0.1-3.6, 3.7-7.3, and 7.4 GBq or more, respectively, compared with a cumulative activity of 0. No trend was noted (P = 0.85). No interaction between (131)I activity and age or between (131)I activity and sex was noted (all P > 0.05). CONCLUSION: (131)I treatment for thyroid cancer did not increase the risk of receiving cataract surgery up to 10 y after treatment. However, further research with direct lens examination and a longer follow-up period is needed to assess subtle and late adverse effects beyond 10 y. PMID- 26837337 TI - 18F-FDG PET/CT: Therapy Response Assessment Interpretation (Hopkins Criteria) and Survival Outcomes in Lung Cancer Patients. AB - The purpose of this study was to evaluate the value of an (18)F-FDG PET/CT-based interpretation system (Hopkins criteria) to assess the therapy response and survival in lung cancer. METHODS: This is an Institutional Review Board-approved, retrospective study. A total of 201 patients with biopsy-proven lung cancer, who underwent therapy assessment (18)F-FDG PET/CT within 6 mo (mean, 7.5 wk) of completion of treatment, were included. Patients were primarily treated with surgical resection, chemotherapy, radiation therapy, or a combination of these treatments. PET/CT studies were interpreted by 2 nuclear medicine physicians, and discrepancies were resolved by a third interpreter. The studies were scored using a qualitative 5-point scale for the primary tumor, mediastinum, distant metastatic site, if present, and overall assessment. Scores 1, 2, and 3 were considered negative and scores 4 and 5 were considered positive for residual disease. Patients were followed for a median of 12 mo (up to 128 mo). Kaplan Meier plots with a Mantel-Cox log-rank test were performed considering death as the endpoint. RESULTS: Overall, the PET/CT studies were positive in 144 (71.6%) and negative in 57 (28.4%) patients. There was substantial agreement between 2 interpreters (R1, R2), with a kappa of 0.78 (P < 0.001). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the Hopkins scoring system were 89%, 80%, 92.8%, 71.4%, and 86.7%, respectively. Overall, PET/CT resulted in starting a new treatment plan in 70.8% of patients with positive residual disease on therapy assessment PET/CT. There was a significant difference in overall survival (OS) between patients who were categorized as positive in comparison to those who were categorized as negative (hazard ratio [HR] = 2.12; 95% confidence interval = 1.44-3.12), which remained significant after adjustment for disease stage, prior clinical suspicion, and primary treatment. Subgroup analysis according to the tumor histology showed that positive Hopkins scoring could significantly predict the OS in both small cell lung cancer (HR = 2.88; log-rank, P = 0.02) and non-small cell lung cancer (HR = 2.01; log-rank, P = 0.001). Similarly, there was a significant difference in OS between patients with positive and negative Hopkins score both in those who had surgical resection as part of the primary treatment (HR = 6.09; log-rank, P < 0.001) and in those who were treated with chemotherapy with or without radiation (HR = 1.60; log-rank, P = 0.02). CONCLUSION: The 5-point qualitative therapy response interpretation for lung cancer has substantial interinterpreter agreement and high accuracy and could significantly predict survival in lung cancer, irrespective of tumor histology and treatment modality. PMID- 26837338 TI - Dixon Sequence with Superimposed Model-Based Bone Compartment Provides Highly Accurate PET/MR Attenuation Correction of the Brain. AB - Simultaneous PET/MR of the brain is a promising technology for characterizing patients with suspected cognitive impairment or epilepsy. Unlike CT, however, MR signal intensities do not correlate directly with PET photon attenuation correction (AC), and inaccurate radiotracer SUV estimation can limit future PET/MR clinical applications. We tested a novel AC method that supplements standard Dixon-based tissue segmentation with a superimposed model-based bone compartment. METHODS: We directly compared SUV estimation between MR-based AC and reference CT AC in 16 patients undergoing same-day PET/CT and PET/MR with a single (18)F-FDG dose for suspected neurodegeneration. Three Dixon-based MR AC methods were compared with CT: standard Dixon 4-compartment segmentation alone, Dixon with a superimposed model-based bone compartment, and Dixon with a superimposed bone compartment and linear AC optimized specifically for brain tissue. The brain was segmented using a 3-dimensional T1-weighted volumetric MR sequence, and SUV estimations were compared with CT AC for whole-image, whole brain, and 91 FreeSurfer-based regions of interest. RESULTS: Modifying the linear AC value specifically for brain and superimposing a model-based bone compartment reduced the whole-brain SUV estimation bias of Dixon-based PET/MR AC by 95% compared with reference CT AC (P < 0.05), resulting in a residual -0.3% whole brain SUVmean bias. Further, brain regional analysis demonstrated only 3 frontal lobe regions with an SUV estimation bias of 5% or greater (P < 0.05). These biases appeared to correlate with high individual variability in frontal bone thickness and pneumatization. CONCLUSION: Bone compartment and linear AC modifications result in a highly accurate MR AC method in subjects with suspected neurodegeneration. This prototype MR AC solution appears equivalent to other recently proposed solutions and does not require additional MR sequences and scanning time. These data also suggest that exclusively model-based MR AC approaches may be adversely affected by common individual variations in skull anatomy. PMID- 26837340 TI - [Cancer risk prediction in post-genome-wide association study era]. PMID- 26837339 TI - Preclinical 89Zr Immuno-PET of High-Grade Serous Ovarian Cancer and Lymph Node Metastasis. AB - The elevation of cancer antigen 125 (CA125) levels in the serum of asymptomatic patients precedes the radiologic detection of high-grade serous ovarian cancer by at least 2 mo and the final clinical diagnosis by 5 mo. PET imaging of CA125 expression by ovarian cancer cells may enhance the evaluation of the extent of disease and provide a roadmap to surgery as well as detect recurrence and metastases. METHODS: (89)Zr-labeled mAb-B43.13 was synthesized to target CA125 and evaluated via PET imaging and biodistribution studies in mice bearing OVCAR3 human ovarian adenocarcinoma xenografts. Ex vivo analysis of tumors and lymph nodes was performed via autoradiography, histopathology, and immunohistochemistry. RESULTS: PET imaging using (89)Zr-DFO-mAb-B43.13 (DFO is desferrioxamine) clearly delineated CA125-positive OVCAR3 xenografts as early as 24 h after the administration of the radioimmunoconjugate. Biodistribution studies revealed accretion of (89)Zr-DFO-mAb-B43.13 in the OVCAR3 tumors, ultimately reaching 22.3 +/- 6.3 percentage injected dose per gram (%ID/g) at 72 h after injection. Most interestingly, activity concentrations greater than 50 %ID/g were observed in the ipsilateral lymph nodes of the xenograft-bearing mice. Histopathologic analysis of the immuno-PET-positive lymph nodes revealed the presence of grossly metastasized ovarian cancer cells within the lymphoid tissues. In control experiments, only low-level, non-specific uptake of (89)Zr labeled isotype IgG was observed in OVCAR3 tumors; similarly, low-activity concentrations of (89)Zr-DFO-mAb-B43.13 accumulated in CA125-negative SKOV3 tumors. CONCLUSION: Immuno-PET with (89)Zr-labeled mAb-B43.13 is a potential strategy for the noninvasive delineation of extent of disease and may add value in treatment planning and treatment monitoring of high-grade serous ovarian cancer. PMID- 26837341 TI - [Genome-wide association study based risk prediction model in predicting lung cancer risk in Chinese]. AB - OBJECTIVE: To evaluate the predictive power of risk model by combining traditional epidemiological factors and genetic factors. METHODS: Our previous GWAS data of lung cancer in Chinese were used in training set (Nanjing and Shanghai: 1473 cases vs. 1962 control) and testing set (Beijing and Wuhan: 858 cases vs. 1 115 control). All the single nucleotide polymorphisms (SNPs) associated with lung cancer risk were systematically selected and stepwise logistic regression analysis was used to select independent factors in the training set. The wGRS (weighted genetic score) was further used to calculate genetic risk score. To evaluate the contribution of the genetic factors, 3 risk models were established by using the training set, i.e. smoking model (based on smoking status) , genetic risk model (based on genetic risk score) and combined model (based on smoke and genetic risk score). The predictability of the models were evaluated by the areas under the receiver operating characteristic (ROC) curves, area under curve (AUC), net reclassification improvement (NRI) and integrated discrimination index (IDI). Besides, the results were further verified in the testing set. RESULTS: In the training set, it was found that the AUC of the smoking, genetic risk and combined models were 0.65 (0.63-0.66), 0.60 (0.59 0.62) and 0.69 (0.67-0.71), respectively. Compared with combined model, the predictive power of other two models significantly declined, the difference was statistically significant (P<0.001). Furthermore, compared with the smoking model, the NRI of the combined model increased by 4.57% (2.23%-6.91%) and IDI increased by 3.11% (2.52%-3.69%) in the training set, the difference was statistically significant (P<0.001). Similarly, in the testing set NRI increased by 2.77%, the difference was not statistically significant (P=0.069) , and IDI increased by 3.16%, the difference was statistically significant (P<0.001). CONCLUSION: This study showed that combining 14 genetic variants with traditional epidemiological factors could improve the predictive power of risk model for lung cancer. The model could be used in the screening of high-risk population of lung cancer in Chinese and provide evidence for the early diagnosis and treatment of lung cancer. PMID- 26837342 TI - [Risk prediction of colorectal cancer with common genetic variants and conventional non-genetic factors in a Chinese Han population]. AB - OBJECTIVE: To understand the association between multiple genetic loci identified by genome-wide association studies (GWASs) and colorectal cancer (CRC) risk, and whether these genetic factors, along with traditional risk factors, could contribute to the colorectal cancer risk prediction in a Chinese Han population. METHODS: A case-control study (1 066 CRC cases and 3 880 controls) was initially conducted to assess the association between 21 recently discovered single nucleotide polymorphisms (SNPs) and CRC risk. Genetic risk score (GRS) and weighted genetic risk score (wGRS) were calculated to evaluate the joint effects of selected loci. Multiple models combining genetic and non-genetic factors were established and receiver operating characteristic curve analysis was used to compare the discriminatory power of different predictive models. RESULTS: There were 7 SNPs significantly associated with CRC susceptibility. As the GRS or wGRS increased, the risk of CRC also increased (trend P=0.002 6 for GRS, trend P<0.000 1 for wGRS). The ORs for highest versus lowest quartile of GRS and wGRS were 1.33 (95% CI: 1.12-1.58, P=0.001 0) and 1.76 (95% CI: 1.45-2.14, P<0.000 1) , respectively. The model incorporating wGRS and traditional risk factors, including sex, age, smoking and drinking, was the best one to predict CRC risk in this population, with an area under curve of 0.593 (95% CI: 0.573-0.613). CONCLUSION: Multiple genetic loci identified by GWASs jointly influenced the CRC risk. The combination of genetic factors and conventional non-genetic factors improved the performance of risk predictive model for colorectal cancer. PMID- 26837343 TI - [Current status of genome-wide association studies (GWAS) on breast cancer and application values of single nucleotide polymorphisms identified from GWAS]. PMID- 26837344 TI - [Genetic risk score: principle, methods and application]. AB - Genetic risk score (GRS) is used for evaluating the effects of genetic susceptible factors in risk prediction models. Five methods are commonly used for GRS: i.e. simple count genetic risk score (SC-GRS), odds ratio weighted genetic risk score (OR-GRS), direct logistic regression genetic risk score (DL-GRS), polygenic genetic risk score (PG-GRS) and explained variance weighted genetic risk score (EV-GRS). This paper summarizes the models, application conditions, advantages and limitations of the five methods. The complexity of prediction models increased along with the inclusion of more susceptible SNPs, some method have been developed to solve the problems, but the effects of new methods needs further evaluation. PMID- 26837345 TI - [Epidemiological survey of atrial fibrillation among Uygur and Han elderly people in Xinjiang Uygur autonomous region]. AB - OBJECTIVE: To investigate prevalence of atrial fibrillation (AF) in Uygur and Han elderly populations in Xinjiang Uygur autonomous region (Xinjiang). METHODS: Epidemiological survey was conducted among the residents selected through stratified random cluster sampling in the southern, northern and eastern Xinjiang. RESULTS: The overall AF prevalence among Uygur and Han elderly people was 3.56%. The crude prevalence of AF was 2.91% among Uygur elderly people and 4.13% among Han elderly people. The sex specific prevalence of AF were 3.19% and 2.61% among Uygur males and females respectively, and 5.01% and 3.31% among Han males and females respectively. The prevalence of valvular AF among Uygur ethnic group was higher than that in Han ethnic group; the prevalence of non-valvular and isolated AF in Han ethnic group were higher than those in Uygur ethnic group. The compliance of aspirin and beta-blocker medication among Han ethnic group was better than that in Uygur ethnic group. The compliance of warfarin medication was poor in both Uygur ethnic group and Han ethnic group. The prevalence of ischemic stroke were 8.82% and 0.98% in Uygur elderly people with or without AF. The prevalence of ischemic stroke were 6.08% and 0.70% in Han elderly people with or without AF. CONCLUSION: The prevalence of AF in elderly people in Xinjiang is similar to the results from other domestic studies, the prevalence of AF in Han elderly people was higher than that in Uygur elderly peoples. PMID- 26837346 TI - [Compliance of antihypertensive drug use in patients with hypertension]. AB - > OBJECTIVE: To understand the compliance of antihypertensive drug use in patients with hypertension. METHODS: A retrospective analysis was conducted among 218 patients with hypertension to understand their drug use compliancy and influencing factors, including side effect of the drugs, drug type, educational level, economic status and drug use length. RESULTS: The factors including disease course, drug type, drug use length and drug side effects, the economy status, educational level, awareness of hypertension related knowledge and psychological reaction could significantly influence the compliance of antihypertensive drug use. Among the patients surveyed, 86.67% of them with poor drug use compliance had only an educational level less than senior high school, 77.33% had poor awareness of hypertension related knowledge. CONCLUSION: The antihypertensive drug use compliance in patients with hypertension is directly related to the outcome of the disease in clinical treatment. It is necessary to take effective measures to improve the treatment compliance and maintain normal blood pressure level of the patients. PMID- 26837347 TI - [Correlation between offspring congenital heart disease and MTHFR 677C/T polymorphism and general status of pregnant women]. AB - OBJECTIVE: To understand the relationship between MTHFR 677C/T polymorphism and general status of pregnant women and offspring congenital heart disease (CHD). METHODS: A case-control study was conducted among the biological mothers of 100 infants with CHD and 100 healthy controls to collect the information about their demographic characteristics, general status during pregnancy and awareness of eugenics. Their MTHFR 677C/T polymorphism and serum homocysteine (HCY), folic acid, vitamin B12 levels were detected. RESULTS: The differences in MTHFR genotype and allele frequency between the two groups were not statistical significant (chi2 =1.08, P=0.582; chi2 =0.53, P=0.468) , but the difference in serum HCY between two groups were statistical significant (t=-8.14, P=0.000). Univariate analysis showed that 14 factors had statistical significances (P<0.05). Multivariate logistic regression analysis indicated that mother's educational level (OR=3.386, 95% CI: 1.279-8.961), annual household income (OR=8.699, 95% CI: 2.177-34.765), chronic disease prevalence (OR=0.343, 95% CI: 0.134-0.881) , awareness of eugenics (OR=0.906, 95% CI: 0.836-0.981), serum HCY level (OR=1.734, 95% CI: 1.458-1.986) and abnormal reproductive history (OR=3.710, 95% CI: 1.217-11.308) were correlated with offspring CHD. CONCLUSION: There was no correlation between MTHFR 677C/T polymorphism of pregnant women and offspring CHD, but low educational level, low annual household income, abnormal reproductive history, low awareness of eugenics and high serum HCY levels of pregnant women might increase the risk of offspring CHD. PMID- 26837349 TI - [Mediating effect of smoking abstinence self-efficacy on association between awareness of smoking hazard and successful smoking cessation]. AB - OBJECTIVE: To estimate the mediating effect of smoking abstinence self-efficacy (SASE) on the association between awareness of smoking hazard and successful smoking cessation. METHODS: A community-based case-control study was conducted in 642 smokers who successfully stopped smoking, and 700 smokers who failed in smoking cessation were used as controls. The awareness of smoking hazard was evaluated by total score of 12 items. The SASE was assessed by using Smoking Abstinence Self-Efficacy (ASES-S). The total effect was classified as direct effect and indirect effect through logistic regression analysis based on the KHB method. RESULTS: After adjusting the potential confounders, including age, age of smoking initiation, occupation, educational level and marital status, the mediating effect of SASE accounted for 6.03% among the total effect of awareness of smoking hazard in those who successfully stopped smoking while the direct effect accounted for 93.97% among the total effect. In the three specific situation of SASE, the mediating effect of SASE accounted for 6.80% (positive/social situations), 3.08% (negative/affective situations) and 2.32% (habit/addictive situations) among the total effect, respectively. CONCLUSION: SASE has part mediating effect to influence on the association between the awareness of smoking hazard and successful smoking cessation. Improving smokers' awareness of smoking hazard may not only promote successful smoking cessation directly, but also contribute to quit smoking through improving the score of SASE. PMID- 26837348 TI - [Association between guardian's first notice of autism symptom of children and time to seek medical care]. AB - OBJECTIVE: To understand the symptoms of autism of children that caused the first notice of guardian, related risk factors and the influence on the time to seek medical care. METHODS: The children with autism aged <5 years were selected from autism rehabilitation centers in Wuhan, Changsha, Haikou, Liuzhou and Changsha between September 2012 and April 2014, and their guardians were retrospectively surveyed by using questionnaire. SPSS 13.0 software was used for statistical analysis. RESULTS: A total of 415 children with autism were included in the study. Including 355 boys (85.54%) and 60 girls (14.46%), the sex ratio was 5.9 : 1. The most common concern of guardian were: language dysplasia (20.72%); ignoring of people or lack of interaction with others (18.55%); repeat and weird action pattern (14.94%). The age when the first symptom occurred, which causing guardians' concern, ranged from 8 months to 28 months, the time when guardian began to concern varied with symptom (chi2 =46.64, P<0.000 1). Guardian's educational level, guardian's contact time with the children, guardian's intimate degree with the children, the age of guardian, family type and tie had no statistical association with the fist autism symptom that caused guardian's concern. The age of the children at first medical care seeking ranged from 10.5 months to 33 months, the time of the first medical care seeking varied with symptom (chi2 =46.10, P<0.000 1). Up to 90.74% of the guardians delayed the medical care seeking of the children with autism, but the symptom specific differences in medical care delay had no statistical significance (chi2 =9.46, P=0.579 6). CONCLUSION: The symptom of the children with autism causing guardian's first notice were mainly verbal communication barrier, social interaction barrier and restricted interests and behaviors. Guardian's educational level and intimate degree with children had no correlation with the symptom which caused guardian's first notice. The time when guardian began to concern and the time for children's medical care varied with guardian's first notice. PMID- 26837350 TI - [Association between walking time and perception of built environment among urban adults in Hangzhou]. AB - OBJECTIVE: To explore the association between walking time and the perception of built environment among local adults in Hangzhou. METHODS: Through multistage stratified random sampling, a total of 1 440 urban residents aged 25-59 years were surveyed in Hangzhou by face-to face interview in 2012. The international physical activity questionnaire-long version (IPAQ-L) was used to assess the physical activity levels, including walking time in the past week. Neighborhood Environment Walkability Scale-Abbreviated (NEWS-A) was used to obtain information about their perception of built environment. Multiple logistic regression was applied to estimate the relationship between waking and the perception of built environment. RESULTS: Among the local adults in Hangzhou, the median of total physical activity was 2 766 met.min-1.week-1, the average walking time per week was 90 min for leisure and 100 min for transportation respectively. After controlling the age, marital status, BMI, educational level, employment, community type and the total PA scores, the leisure-time walking was negatively related to the accessibility to stores, facilities and other things for both man (OR=0.764, 95% CI: 0.588-0.992) and woman (OR=0.633, 95% CI: 0.481-0.833). In sex specific analysis, the leisure-time walking was negatively related with the residential density (OR=0.997, 95% CI: 0.996-0.999) while transportation related walking was positively related with walking/cycling way scores (OR=1.537, 95% CI: 1.138-2.075) in females. In contrast, there were no significant associations between perception of built environment and transportation related walking in males. CONCLUSION: Improving the built environment, such as the walking/cycling way, might be useful to increase the transportation related walking time for adults. The sex specific differences need to be considered in the environment intervention for walking promotion. PMID- 26837351 TI - [Evaluation of perceptions of physical activity related built environment among urban adults with different characteristics in Hangzhou]. AB - OBJECTIVE: To understand the perceptions of physical activity-related built environment among urban adults in Hangzhou. METHODS: A face-to-face interview was conducted among the urban residents aged 25-59 years selected through multistage stratified random sampling in Hangzhou in 2012. The Neighborhood Environment Walkability Scale-Abbreviated (NEWS-A) was used to assess the perception of built environment among residents, including residential building density, the diversities of stores, facilities and others, the accessibility to public service, the street connectivity, walking/cycling facilities, aesthetics, traffic safety, and public security. The multilevel logistic regression model was used to assess the demographic characteristics, BMI and other factors' influence on people's perceptions. RESULTS: Among 1 362 local residents surveyed, no sex, martial status and occupation specific significant differences in the perception of built environment were found. After adjusting other factors, the age group 45 59 years was positively related to the score of street connectivity (OR=2.02, 95% CI: 1.30-3.15). The educational level of college or higher was positively associated with the score of residential building density (OR=1.97, 95% CI: 1.29 3.00) but negatively associated with the score of facility variety (OR=0.65, 95% CI: 0.43-0.97). Overweight or obesity was negatively related to the scores of walking/cycling ways (OR=0.67, 95%CI: 0.48-0.95) and public security (OR=0.75, 95% CI: 0.57-0.99). Compared with the class I residential area, the people in class III residential area had lower perception scores on facility diversity (OR=0.11, 95% CI: 0.04-0.30), accessibility to public service (OR=0.33, 95% CI: 0.11-0.95), street connectivity (OR=0.30, 95% CI: 0.11-0.86) and traffic safety (OR=0.39, 95% CI: 0.17-0.91). CONCLUSION: The perceptions of physical activity related built environment was associated with age, educational level, BMI and residential area. The personal characteristics should be considered while performing environment intervention on physical activity. PMID- 26837352 TI - [A comparative study on iodine nutrition and thyroid function of different population in urban and rural areas of Wuwei, Gansu province]. AB - OBJECTIVE: To understand the iodine nutrition and thyroid function of different population in urban and rural areas of Gansu province and provide evidence for iodine supplementation. METHODS: A cross-sectional survey was performed in urban and rural children, adults, pregnant women and breastfeeding women in Wuwei from April 2009 to January 2010. Urine and fasting blood samples were collected from the subjects. Urine iodine content was measured with arsenic cerium catalytic spectrophatometry. The thyroid-stimulating hormone (TSH) , free thyroid hormone (FT4) and three free triiodothyronine (FT3) were detected by using direct chemiluminescence immunoassy. Non parametric test was used to compare the urinary iodine and TSH group. t test was used to compare FT4, FT3. chi2 test was used to compare the rate. RESULTS: The medians of urinary iodine level (ug/L) were 358.6, 189.0, 255.4 and 239.5 in urban children, adults, pregnant women and breastfeeding women and 387.6, 258.5, 172.8 and 215.3 in rural children, adults, pregnant women and breastfeeding women respectively. The median of urinary iodine of urban adults was significantly lower than that in rural adults (Z=-4.020, P=0.000) and the medians of urinary iodine level of urban pregnant women was higher than that in rural pregnant women (Z=1.424, P=0.035). The mean value of FT3 in rural pregnant women and breastfeeding women were higher than that in urban groups (t=-3.933, P=0.000; t=-2.259, P=0.026). The mean value of FT4 in urban adults was higher than that in rural adults (t=3.539, P=0.001). The positive rate of TGAb and TMAb in rural pregnant women and breastfeeding women were 43.6%, 56.4% and 33.3%, 35.6%, respectively, which were higher than those in urban groups. Subclinical hypothyroidism in all thyroid function disorders was common in all the groups. No statistical significant difference in all thyroid function disorders were found in different population. CONCLUSION: The iodine nutrition were in good status in both urban population and rural population, the children's iodine nutrition was surplus. Statistical differences existed in iodine nutrition status or thyroid hormone level between urban and rural adults, pregnant women and breastfeeding women. PMID- 26837353 TI - [Etiological surveillance for diarrhea in Shanghai from August 2013 to July 2014]. AB - OBJECTIVE: To understand the pathogen spectrum and epidemiological characteristics of diarrhea cases in Shanghai from August 2013 to July 2014. METHODS: The survey was conducted in 23 hospitals at different levels randomly selected in Shanghai, the diarrhea cases seeking medical care in these hospitals were sampled, and stool samples were collected from them for pathogen isolation. RESULTS: Among 3 467 stool samples detected, 1 561 were positive for at least 1 pathogen (45.02%). A total of 6 kinds of bacteria and 5 kinds of viruses were detected. The positive rate for bacterium was 13.46%, mainly Vibrio parahaemolyticus (172 cases) and Salmonella (143 cases). The positive rate for virus was 27.75%, mainly Norovirus (471 cases) and Rotavirus (312 cases). The positive rates peaked obviously in summer and during autumn-winter. The positive rate of virus was higher than that of bacterium during autumn-winter, and the positive rate of bacterium was higher than that of virus in summer, the differences were statistically significant (P<0.05). Stratified analysis showed the constituent ratio of virus positive samples during November-February was highest among all age groups, however, the difference was not statistically significant (P>0.05). The constituent ratio of bacterium positive samples during June-September was highest in all age groups, the difference was statistically significant (P<0.05). The proportion of the cases with fever in bacterium positive group (19.06%) was higher than those in virus positive group (10.91%), the difference had statistically significance (P<0.05). CONCLUSION: The pathogen spectrum of diarrhea was relatively wide in Shanghai and the seasonality of the incidence was obvious. Specific etiological surveillance and control strategies should be strengthened among risk groups in different seasons. PMID- 26837355 TI - [Prevalence of informing of HIV infection status during medical care seeking and influential factors among people living with HIV/AIDS]. AB - OBJECTIVE: To understand the prevalence of informing doctors of the HIV infection status during medical care seeking and influential factors among people living with HIV/AIDS. METHODS: The study was conducted among people living with HIV/AIDS in 7 provinces in China, including those receiving HIV test, HIV counsel and HIV infection treatment. The data were analyzed with software SAS 9.2. Chi-square test was used to compare the informing rates in patients with different characteristics. Univariate and multivariate logistic regression analyses were conducted to identify the influential factors. RESULTS: Of the 2 432 HIV/AIDS patients, 49.7% (716/1 442) didn't inform the doctors of their HIV infection status actively. The non-active informing rate was 51.9% (559/1 077) in males, 62.9% (212/337) in age group 18-30 years old, 58.1% (555/955) in those with a educational level >primary school, 65.7% (241/367) in those working in private/joint companies or the self employed and 62.5% (197/315) in those living in small cities. The non active informing rate was highest in those infected through sexual contact (66.3%, 275/415). Multivariate logical regression analysis indicated that those infected through illegal blood donation would like to inform of the HIV infection status actively (OR=0.083, 95% CI: 0.049-0.141) , but those working in private/joint companies or the self employed would like not to inform of the HIV infection status actively (OR=1.531, 95% CI: 1.017-2.304). CONCLUSION: The non active informing rate of HIV infection status was high in people living with HIV/AIDS. It is necessary to conduct the targeted health education to encourage people living with HIV/AIDS to inform of their HIV infection status actively. PMID- 26837354 TI - [A community-based seroepidemiological survey of hepatitis B among adults in Chaoyang district, Beijing]. AB - OBJECTIVE: To understand the positive rates of hepatitis B surface antigen (HBsAg) and surface antibody (anti-HBs) among adults aged >=18 years in communities in Chaoyang district, Beijing. METHODS: HBsAg and anti-HBs were tested with ELISA reagents for participants in the Community Diagnosis Survey (3 000 person were sampled in each community according to the age and sex distribution of the residents) in all 42 communities in Chaoyang district by Beijing Center for Disease Control and Prevention (CDC) and Chaoyang CDC. The data of 35 communities in which at least 1 000 adults were tested were analyzed. RESULTS: A total of 78 100 adults were tested for HBsAg and anti-HBs in the 35 communities. The crude positive rate of HBsAg was 2.24% (95% CI: 2.13%-2.34%). The highest age-specific HBsAg positive rate was 3.00% (95% CI: 2.56%-3.44%) for those aged 40-44 years and the lowest age-specific HBsAg positive rate was 1.69% (95% CI: 1.29%-2.09%) for those aged 18-24 years, respectively. A obvious difference in community- based HBsAg positive rate was founded with the highest of 10.68% (95% CI: 9.43%-11.94%) and lowest of 0.24% (95% CI: 0.13%-0.38%). HBsAg positive rate was significantly lower in local residents than in participants with household registered in other provinces (1.97% vs. 2.98%, P<0.01), but the sex specific difference in HBsAg positive rate was relatively smaller (2.45% in males and 2.07% in females, P<0.01). The multivariate logistic regression analysis showed that age, community, occupation, residence status and sex were all associated with positive rate of HBsAg (P<0.01). The overall positive rate of anti-HBs was 30.85% (95% CI: 30.53%-31.18%), and the highest was 38.10% in age group 18-24 years (95% CI: 36.58%-39.61%) and the lowest was 28.88% in age group 75- years (95% CI: 27.62%-30.15%), respectively. Up to 67.02% of the subjects were both HBsAg and anti-HBs negative (95% CI: 66.69%-67.35%), and the age specific difference was not significant. But significant differences in anti-HBs positive rate and the negative rate of both HBsAg and anti-HBs were found across communities. CONCLUSION: The overall positive rate of HBsAg was at a moderate low level among adults in Chaoyang, but the age specific positive rate was high in the middle-aged and the population specific positive rate was high in participants with household registered in other provinces, therefore, the prevention and control of hepatitis B in Chaoyang should be focused on the middle aged people and participants with household registered in other provinces. The community specific differences in the positive rate of HBsAg and anti-HBs across communities need to be further studied. PMID- 26837356 TI - [Drop out of antiretroviral therapy in people living with AIDS/HIV and related factors in Nanjing and Yuncheng]. AB - OBJECTIVE: To understand the incidence of drop out of antiretroviral therapy (ART) in people living with AIDS/HIV and related factors in Nanjing, Jiangsu province, and Yuncheng, Shanxi province. METHODS: Retrospective cohort analysis was conducted. The cumulative incidence curves of drop out of ART, mortality and drug withdrawal were drawn with Kaplan-Meier method. The related factors were identified with Cox proportional hazards regression model. RESULTS: A total of 1 006 patients were included in Yuncheng, the median length of ART follow-up was 49.59 months (QR: 20.02-92.84), and 976 patients were included in Nanjing, the median length of ART follow-up was 19.93 months (QR: 11.48-34.07). The cumulative incidence of drop out of ART at 3 months, 6 months, 1 year, 2 years, 4 years, 8 years after ART was 8.19%, 9.23%, 11.08%, 13.75%, 17.74%, 27.66% in Yuncheng, and 3.01%, 5.17%, 7.47%, 10.97%, 17.45%, 28.72% in Nanjing respectively. Age, marital status, infection route, baseline CD4 cell count, the clinical stage classified by WHO at the end of the observation were correlated with the drop out of ART. CONCLUSION: In order to reduce the drop out of ART among people living with AIDS/HIV, it is necessary to conduct effective interventions targeting the patients with young age, the patients who divorced/widowed, the patients who were intravenous drug users, the patients with higher CD4 cell count at the beginning of ART and clinical stage III or IV at the end of the follow-up and increase the coverage of HIV test. PMID- 26837357 TI - [Analysis on willingness to receive human papillomavirus vaccination among risk males and related factors]. AB - OBJECTIVE: To understand the willingness to receive human papillomavirus (HPV) vaccination of men who have sex with men (MSM) and the male clients of sexually transmitted disease (STD) clinics and related factors in China. METHODS: MSM were enrolled from the community through snowball sampling and male clients of STD clinics were enrolled from a sexual health clinic through convenience sampling in Wuxi, China. A questionnaire survey on the subjects' socio-demographic characteristics and the awareness of HPV was conducted. RESULTS: A total of 186 MSM and 182 STD clients were recruited. The awareness rates of HPV were 18.4% and 23.1%, respectively and the awareness rates of HPV vaccination were 10.2% and 15.4%, respectively. STD clinic clients (70.9%) were more likely to receive HPV vaccination than MSM (34.9%) (chi2 = 47.651, P<0.01). Only 26.2% of MSM and 20.2% of STD clinic clients were willing to receive free HPV vaccination before the age of 20 years. Multivariate logistic regression analysis showed that MSM who had passive anal sex (OR=2.831, 95% CI: 1.703-13.526) , MSM who never used condom in anal sex in the past 6 months (OR=3.435, 95% CI: 1.416-20.108) , MSM who had been diagnosed with STDs (OR=1.968, 95% CI: 1.201-8.312) and STD clinic clients who had commercial sex with females in the past 3 months (OR=1.748, 95% CI: 1.207 8.539) , STD clinic clients who never used condom in commercial sex in the past 3 months (OR=1.926, 95% CI: 1.343-5.819) and STD clinic clients who had been diagnosed with STDs in past 12 months (OR=2.017, 95% CI: 1.671-7.264) were more likely to receive free HPV vaccination. CONCLUSION: Sexually active MSM and male clients in STD clinics in China had lower awareness of the HPV related knowledge. Their willing to receive HPV vaccination were influenced by their behavior related factors. It is necessary to strengthen the health education about HPV and improve people's awareness of HPV vaccination. PMID- 26837358 TI - [Analysis on dynamic variations of CD4-Positive T-Lymphocytes counts and influencing factors among patients receiving highly active antiretroviral therapy in Guangxi Zhuang autonomous region]. AB - OBJECTIVE: To understand dynamic variation of CD4-Positive T-Lymphocytes counts and influencing factors among patients receiving highly active anti-retroviral therapy (HAART) in Guangxi. METHODS: Adult patients who received antiviral treatment for the first time after 1 January 2013 were selected. Their CD4 Positive T-Lymphocytes counts at baseline, 6 months and 12 months after treatment were analyzed. By using the general linear model repeated measures ANOVA, CD4 Positive T-Lymphocytes dynamic variations and influencing factors were described and analyzed. RESULTS: The average CD4 cell counts of 4 082 patients at baseline, 6(th) months and 12(th) months were (195.3 +/- 155.7) cells/mm3, (331.9 +/- 202.6) cells/mm3 and (380.9 +/- 221.3) cells/mm3, respectively. The time specific differences in CD4-Positive T-Lymphocytes count among them were statistically significant (F=3 161.124, P=0.000). CD4-Positive T-Lymphocytes counts increased over time after treatment. The main influencing factors were sex, age, baseline CD4 cell count, medication, discontinuation of treatment or dose miss. Influenced by sex, age, medication, discontinuation of treatment or dose miss, the increased CD4-Positive T-Lymphocytes count showed a linear trend. Influenced by baseline CD4-Positive T-Lymphocytes counts and dose miss, the increase of CD4-Positive T Lymphocytes count showed a trend which was conformed to quadratic curvilinear equation. CONCLUSION: CD4-Positive T-Lymphocytes counts among patients receiving HAART in Guangxi were influenced by many factors. It is necessary to select the time to start treatment according to patient's characteristics to get good outcome. PMID- 26837359 TI - [Quality evaluation of hospitalized hepatitis C cases reporting in Henan province, 2014]. AB - OBJECTIVE: To evaluate the network reporting quality of hepatitis C cases in Henan province in 2014. METHODS: The data of hepatitis C case reporting was collected from selected medical institutions in Henan province in 2014. According to current reporting standards, the evaluation of reporting rate, the timely reporting rate, the underreporting rate, the false reporting rate and the anti HCV positive and HCV-RNA positive reporting rate of hepatitis C cases were evaluated. RESULTS: A total of 2 778 hospitalized hepatitis C cases in 170 medical and health institutions were surveyed, the reporting rate was 84.10%, the timely reporting rate was 100.00%, the underreporting rate was 15.90%, the false reporting rate was 13.17% and the anti-HCV positive and HCV-RNA positive reporting rate was 91.06%. The coincidence rate of diagnosis and reporting was 58.61%, the coincidence rate of acute or chronic cases was 30.93%. More clinical diagnosed cases were underreported. The coincidence rate of laboratory confirmed cases reporting were low. The diagnosis and reporting coincidence rate was low in provincial medical institutions. CONCLUSION: In Henan, the hepatitis C case reporting rate was high, the anti-HCV positive and HCV-RNA positive reporting rate needs to be improved. The coincidence rate of hepatitis C reporting was low. Underreporting and false reporting still existed. The quality of hepatitis C reporting in provincial medical and health institutions needs to be improved. PMID- 26837360 TI - [Study on burden of disease in Chongqing, 2010-2013]. AB - OBJECTIVE: To analysis the burden of diseases (BOD) and economic burden of disease (EBOD) in Chongqing and provide scientific evidence for effective prevention and control of diseases. METHODS: The burden of diseases of Chongqing were estimated by use of disability-adjusted life year (DALY) from 2010 to 2013, two-step method was used in the calculation of direct economic burden of diseases. DALY combined with the human capital method were used to measure the indirect economic burden. RESULTS: From 2010 to 2013, DALY loss by all causes for the residents in Chongqing were 123.90, 127.01, 123.30 and 125.99 person year per thousand persons, respectively. The diseases mainly included non-communicable diseases, accounting for 83%-87%, followed by injure and infectious diseases. The five leading diseases of BOD in Chongqing were respiratory system disease, circulatory system disease, malignant tumor, accidental death, neuropsychiatric disease, respectively. The total economic burden of diseases was 1 621.34 million yuan RMB in 2013. The direct and indirect economic burden of diseases were 794.42 million yuan RMB and 826.92 million yuan RMB, which could be attributed to circulatory system disease, respiratory system diseases, injury, malignant tumor and muscle bones and connective tissue diseases. CONCLUSION: Respiratory system disease, circulatory system diseases, malignant tumor, and injury have caused heavy burden both in people's health and economic status in Chongqing. It is necessary to take effective measures to prevent and control these diseases. PMID- 26837361 TI - [Epidemiological characteristics of hospital reported road traffic injuries case in Tianjin, 2013]. AB - OBJECTIVE: To understand the distribution of reported road traffic injuries case in Tianjin from January to December 2013. METHODS: The injury data was collected from the disease surveillance system which covered all the areas in Tianjin. All the reported injury cases were at their first medical care seeking in sentinel hospitals from 1 January 2013 to 31 December 2013. RESULTS: A total of 26 405 injury cases were reported, including 103 deaths (0.4%), during this period with the incidence of 263.01/100 000. The male to female ratio of the cases was 1.68: 1 and average age of the cases was (40.24 +/- 17.58) years. The injuries caused by motor vehicle traffic accident accounted for 74.0% (19 547 cases) and the non motor vehicle traffic accident caused cases accounted for 26.0% (6 858). The first four areas with higher incidence were Binhai (684.86/100 000) , Dongli (634.03/100 000) , Xiqing (519.83/100 000) and Jinnan (504.12/100 000) districts. The three districts with lower incidence were Heping (44.69/100 000), Nankai (52.36/100 000) and Hedong (64.34/100 000) districts. The mild, moderate and serious cases accounted for 59.7% (15 771 cases), 33.1% (8 747 cases) and 6.8% (1 783 cases) respectively. The differences in incidence among different districts and age groups were statistical significant (P<0.005). The death number in Tanggu district was highest, accounting for (26.21%) of the total, and age specific death number was highest in age group 45-64 years, accounting for 46.60% of the total. CONCLUSION: The case number and severity of road traffic accident caused injury varied with area and age group in Tianjin. It is necessary to develop targeted prevention and control measures to reduce the incidence of road traffic accident related injuries. PMID- 26837362 TI - [Hierarchical regionalization for spatial epidemiology: a case study of thyroid cancer incidence in Yiwu, Zhejiang]. AB - OBJECTIVE: Sporadic cases occurring in mall geographic unit could lead to extreme value of incidence due to the small population bases, which would influence the analysis of actual incidence. METHODS: This study introduced a method of hierarchy clustering and partitioning regionalization, which integrates areas with small population into larger areas with enough population by using Geographic Information System (GIS) based on the principles of spatial continuity and geographical similarity (homogeneity test). This method was applied in spatial epidemiology by using a data set of thyroid cancer incidence in Yiwu, Zhejiang province, between 2010 and 2013. RESULTS: Thyroid cancer incidence data were more reliable and stable in the new regionalized areas. Hotspot analysis (Getis-Ord) on the incidence in new areas indicated that there was obvious case clustering in the central area of Yiwu. CONCLUSION: This method can effectively solve the problem of small population base in small geographic units in spatial epidemiological analysis of thyroid cancer incidence and can be used for other diseases and in other areas. PMID- 26837363 TI - [Quantile regression analysis of health-related quality of life of rural residents in Shaanxi and its associated factors]. AB - OBJECTIVE: This study aimed to apply quantile regression to study Hanzhong rural residents health survey data, explore the local distribution characteristics of health-related quality of life (HRQOL) and influencing factors and present the value of quantile regression applying in analysis of HRQOL. METHODS: In this cross-sectional population-based study, we evaluated the HRQOL of 2 737 subjects through filling Short-Form Health Survey (SF-36). Quantile regression model was used to compare MCS and PCS scores and evaluate the associated factors. RESULTS: With different quantiles MCS and PCS score, the associated factors and influence degree were different. In general, the influences of marital status, educational level, physical activity, history of disease and HRQOL in the part of the percentile scores were significant. CONCLUSION: Analysis of the distribution of HRQOL of rural residents in Hanzhong and influencing factors would benefit the improvement of HRQOL of local residents. PMID- 26837364 TI - [Study on co-infection of tick-borne pathogens in Ixodes persulcatus in Charles Hilary, Xinjiang Uygur autonomous region]. AB - OBJECTIVE: To study the co-infection of tick-borne pathogens in Ixodes persulcatus collected in Charles Hilary, Xinjiang Uygur autonomous region (Xinjiang). METHODS: Ticks were collected by flagging in grassy areas in Charles Hilary, Xinjiang from June 2012 to June 2013. The 5S-23S rRNA intergenic region from Borrelia (B.) burgdorferi, 16S rRNA gene from Anaplasma, ompA gene from spotted fever group Rickettsia, com1 gene from Coxiella (C.) burneti and Nss-rRNA gene from Babesia were amplified with nested polymerase chain reaction (nested PCR) , respectively. RESULTS: Among 204 Ixodes persulcatus, 104 were positive for tick-borne pathogens with the positive rate of 50.98%, and among them the positive rates of B. burgdorferi, spotted fever group Rickettsia and Anaplasma phagocytophilum were 34.31% (n=70), 28.92% (n=59), 9.31% (n=19) , respectively. And no C. burnetii and Babesia were detected. The overall co-infection rate was 19.12% (39/204), the co-infection rate was 16.18% (33/204) for B. garinii and spotted fever group Rickettsia, 4.90% (10/204) for B. burgdorferi and Anaplasma phagocytophilum, 2.94% (6/204) for spotted fever group Rickettsia and Anaplasma phagocytophilum and 2.45% (5/204) for B. burgdorferi, Anaplasma phagocytophilum and spotted fever group Rickettsia. CONCLUSION: The results indicated that the natural co-infections of B. garinii, B. afzelii, Anaplasma phagocytophilum and spotted fever group Rickettsia existed in Charles Hilary Ixodes persulcatus collected in Xinjiang. PMID- 26837365 TI - [Study on VNTR diversity of clinical Mycobacterium tuberculosis isolates from Qinghai]. AB - OBJECTIVE: To investigate the variable number tandem repeats (VNTR) genetic polymorphisms, genotyping and distribution pattern of clinical Mycobacterium (M.) tuberculosis isolates from Qinghai province. METHODS: The clinical M. tuberculosis strains isolated from the patients with tuberculosis and related background data were collected from Qinghai Provincial Center for Disease Control and Prevention from 2009 to 2012. Genotyping was conducted by using multiple locus VNTR analysis (MLVA). Genomic DNA was extracted and 15 VNTR loci were amplified with PCR and the PCR products were detected with gel electrophoresis. The VNTR diversity and clusters of genotyping were analyzed with BioNumerics (Version 5.0). RESULTS: A total of 251 clinical M. tuberculosis isolates were analyzed with 15 VNTR loci showing that there were great genetic diversity in these isolates. Six of the 15 VNTR loci, showed that the Hunter-Gaston index (HGI) were higher than 0.6, in which the highest resolution was MIRU26. The clusters of genotyping showed that these isolates could be categorized into four gene clusters and 238 genotypes. The four gene clusters accounted for 4.9%, 91.9%, 1.6% and 1.6% of the clinical isolates, respectively. CONCLUSION: The results showed that there is great variety of VNTR genetic polymorphisms in clinical M. tuberculosis isolates in Qinghai province. PMID- 26837366 TI - [Study on virulence factors of Candida tropicalis isolated from clinical samples]. AB - OBJECTIVE: To determine the in vitro production of virulence factors for Candida (C.) tropicalis, including aspartyl proteinases, phospholipases and hemolytic activities, describe the regulation of virulence factors varying with time in C. tropicalis, and analyze the differences in aspartyl proteinases and hemolytic activities of C. tropicalis isolated from anatomically distinct sites. METHODS: A total of 64 C. tropicalis strains were spot-inoculated onto bovine albumin agar, egg yolk agar and sheep blood agar plates, respectively. Then the plates were incubated for 24, 48 and 72 hour at 37 degrees C, respectively. The aspartyl proteinases, phospholipase and hemolytic activities were determined at each time point, respectively. RESULTS: All the C. tropiclais isolates showed positive aspartyl proteinases and hemolytic activities at each time point, but no phospholipases activity was detected in C. tropicalis. On comparison of aspartyl proteinases and hemolytic activities at different time points, aspartyl proteinases activity at 48 and 72 hour was higher than that at 24 hour. During 72 hour, hemolytic activity of C. tropicalis increased. No statistical significant differences in aspartyl proteinases and hemolytic activities of C. tropicalis were observed among different infection sites (P=0.368 and 0.985). CONCLUSION: The C. tropicalis clinical isolates in China have aspartyl proteinases activity, hemolytic activity, but have no phospholipase activity. PMID- 26837367 TI - [Association between type 2 diabetes in Uygur and polymorphisms of SLC30A8 and its interaction with smoking]. AB - OBJECTIVE: To explore the relationship between the polymorphism of solute carrier family 30, member 8 (SLC30A8) gene and type 2 diabetes mellitus (T2DM) in Uyhgur in Xinjiang and further analyze the interaction between SLC30A8 gene polymorphism loci and smoking. METHODS: A case control study, including 1 000 patients with T2DM and 1 010 non-diabetic controls, was conducted in Xinjiang. All the subjects were Uygur and the age difference between the two groups was within 3 years. Physical examination and blood biochemical detection were performed to obtain personal clinical parameters. Genomic DNA was extracted from peripheral blood leukocytes. The single nucleotide polymorphism (SNP) of SLC30A8 of all the subjects was tested by using MALDI-TOF. Statistical analyses were performed with SPSS 16.0. Bootstrap method was used to calculate 95% confidence intervals of RERI, AP and S. RESULTS: After adjusting BMI, SBP, TC, HDL-C and LDL-C, rs13266634 of SLC30A8 gene genotype frequency and allele frequency distribution had statistical differences (P<0.05). Rs13266634 of risk allele were C, OR was 1.194 (95% CI: 1.044-1.366). In addition, the data from genotype distribution analysis under different models showed that significant association between rs13266634 and T2DM in dominant model, OR was 1.640 (95% CI 1.072-2.510). The product of rs13266634 with the active smoking or passive smoking had no statistical significance (P>0.05) , indicating there were no multiplication interaction among them. Additive interactions index of RERI, AP and S and its 95% confidence interval of rs13266634 and active smoking, rs13266634 and passive smoking were 0.301 (-1.314-0.712), 0.204 (-0.854-0.446), 0.612 (0.186-2.013) and 0.125 (-0.805-1.055), 0.052 (-0.353-0.456), 1.096 (0.500-2.403) respectively, indicating there were no significant additive interaction among them. CONCLUSION: Rs13666334 of SLC30A8 gene is associated with the susceptibility of T2DM in Uygur, and its protective genotype might be TT. Passive smoking might increase the risk of T2DM in Uygur. PMID- 26837368 TI - [Bibliometric analysis of worldwide literature in research of intimate partner violence in the world in recent 10 years]. AB - OBJECTIVE: To analyze and reveal the worldwide hot topic and trend of the researches of intimate partner violence (IPV) during the past 10 years, and provide evidence for the related researches in China. METHODS: Relevant literatures included by PubMed database from 2005 to 2014 were analyzed quantitatively by using bibliographic item co-occurrence mining system (BICOMS). SPSS 20.0 statistical software was used to identify the high frequent key words of published articles to draw clustering relationship picture and Chi-square analysis was conducted to test the change trend of hot key words. RESULTS: Totally 3 257 IPV related articles were retrieved, and the number of the published papers was increasing in last decade, especially during the past three years. Study hot topics included IPV related damage and diseases, epidemiological studies, social support and IPV prevention and control. Chi-square analysis showed, during 2010-2014, the research mainly focused on the relationship between IPV and HIV infection (2.0% vs. 1.0%, chi2 = 4.471, P=0.034) , and pregnant women and others were also included in the target population (1.2% vs. 0.4%, chi2 = 4.805, P=0.028). CONCLUSION: Worldwide research on IPV mainly focused on four aspects in recent ten years, but the relationship between IPV and HIV infection became a new research hot topic and pregnant women and others became new target populations in recent 5 years. PMID- 26837369 TI - [Quantitation and qualitation: a dimension of integration of researches of anthropology and epidemiology]. PMID- 26837370 TI - [The sources and application of big data in healthcare]. PMID- 26837371 TI - Primary angiitis of the central nervous system: avoiding misdiagnosis and missed diagnosis of a rare disease. AB - Primary angiitis of the central nervous system (PACNS) is an extremely rare condition, defined as a vasculitis limited to the CNS with no identifiable cause. Its presentation is non-specific and includes headache, cognitive dysfunction and focal neurological signs. Laboratory studies, neuroimaging and angiography are neither sufficiently sensitive nor specific for diagnosis; a definitive diagnosis requires brain biopsy. As a result, PACNS is commonly misdiagnosed. Here, we review its clinical, laboratory and radiological features, and focus on avoiding common diagnostic pitfalls. PMID- 26837372 TI - Safe use of perampanel in a carrier of variegate porphyria. PMID- 26837373 TI - Management of spontaneous intracranial hypotension. PMID- 26837374 TI - A taxing case. PMID- 26837375 TI - Cerebral palsy. AB - Cerebral palsy has always been known as a disorder of movement and posture resulting from a non-progressive injury to the developing brain; however, more recent definitions allow clinicians to appreciate more than just the movement disorder. Accurate classification of cerebral palsy into distribution, motor type and functional level has advanced research. It also facilitates appropriate targeting of interventions to functional level and more accurate prognosis prediction. The prevalence of cerebral palsy remains fairly static at 2-3 per 1000 live births but there have been some changes in trends for specific causal groups. Interventions for cerebral palsy have historically been medical and physically focused, often with limited evidence to support their efficacy. The use of more appropriate outcome measures encompassing quality of life and participation is helping to deliver treatments which are more meaningful for people with cerebral palsy and their carers. PMID- 26837376 TI - Influence of Coformer Stoichiometric Ratio on Pharmaceutical Cocrystal Dissolution: Three Cocrystals of Carbamazepine/4-Aminobenzoic Acid. AB - Cocrystallization is a technique to optimize solid forms that shows great potential to improve the solubility of active pharmaceutical ingredients (APIs). In some systems, an API can form cocrystals in multiple stoichiometries with the same coformer. However, it remains unclear how coformer stoichiometry influences solubility. This paper investigates the pharmaceutical:coformer pair carbamazepine (CBZ)/p-aminobenzoic acid (PABA); both CBZ/PABA 1:1 and 2:1 cocrystals are known, and a novel 4:1 CBZ/PABA cocrystal is reported here. The 4:1 cocrystal is structurally characterized, and phase stability data suggest that it is a thermodynamically unstable form. Dissolution experiments show that there is no correlation between the cocrystal stoichiometry and dissolution rate in this system. On the other hand, with the relatively weak intermolecular interactions, metastable forms can be beneficial to dissolution rate, which suggests that more effort should be devoted to cocrystal production with kinetic growth methods. PMID- 26837377 TI - The functional results of tibial shaft fractures treated with intramedullary nail compressed by proximal tube. AB - Nailing of tibial shaft fractures is considered the gold standard surgical method by many surgeons. The aim of this retrospective study was to investigate and compare the clinical outcome of tibial shaft fractures treated with intramedullary nails compressed by proximal tube and conventional intramedullary interlocking nails. Fifty-seven patients with tibial shaft fractures, treated with intramedullary nails compressed by proximal tube (n = 32) and the conventional interlocking nails (n = 25), were reviewed. All fractures except for one were united without any additional surgical intervention in the proximal compression tube nail group, whereas in the conventional interlocking nail group, six patients needed dynamization surgery (p = 0.005) and three cases of nonunion were recorded. In the proximal compression tube nail group, faster union occurred in 20 +/- 2 (16-24) weeks (mean +/- SD; range) without failure of locking screws and proximal nail migration, whereas in the conventional interlocking nail group, union occurred in 22 +/- 2.5 (17-27) weeks (p = 0.001) with two failures of locking screws and two proximal nail migration. The proximal compression tube nail system is safer than the conventional nailing methods for the treatment for transverse and oblique tibial shaft fractures with a less rate of nonunion, proximal locking screw failure and proximal nail migration. PMID- 26837378 TI - Spinal subarachnoid hemorrhage in cortical superficial siderosis after apixaban and clopidogrel therapy. PMID- 26837379 TI - Platelet reactivity after administration of third generation P2Y12-antagonists does not depend on body weight in contrast to clopidogrel. AB - The current standard of antiplatelet therapy for patients with myocardial infarction (MI) includes the P2Y12-receptor antagonist clopidogrel, prasugrel or ticagrelor. While it has been shown that platelet reactivity after clopidogrel administration depends on factors such as body weight, it is not known if these factors have an effect on the activity of prasugrel or ticagrelor. Thus, this study aimed to analyse factors associated with high residual platelet reactivity after administration of third generation P2Y12-antagonists compared to clopidogrel. In a single centre registry the antiplatelet effect of clopidogrel, prasugrel or ticagrelor was investigated by aggregometry in patients after MI. To assess the overall capacity of platelet aggregation whole blood was induced with thrombin receptor activating peptide (TRAP; 32 uM). To specifically quantify the effect of P2Y12-antagonists, blood was stimulated with 6.4 uM adenosine diphophosphate (ADP). Relative ADP induced aggregation (r-ADP-agg) was defined as the ADP-TRAP-ratio to reflect an individual degree of P2Y12-dependent platelet inhibition. Platelet function of 238 patients was analysed [clopidogrel (n = 58), prasugrel (n = 65), ticagrelor (n = 115)]. It was found that the r-ADP-agg correlated significantly with body weight in patients after clopidogrel administration (r = 0.423; p < 0.001). In contrast, this association was not present in patients after prasugrel (r = -0.117; p = 0.354) or ticagrelor (r = 0.082; p = 0.382) administration. Comparison of the correlation coefficients showed a significant difference (p = 0.003). In contrast to clopidogrel, platelet reactivity after administration of prasugrel or ticagrelor does not depend on body weight in patients after MI. Hence, our mechanistic data support the results of large clinical trials indicating that patients with high body weight do not need to be treated with increased doses of third generation P2Y12-antagonists to achieve sufficient platelet inhibition (registry for patients after myocardial infarction treated with antiplatelet agents; DRKS00003146). PMID- 26837380 TI - Determination of contamination levels of Pb, Cd, Cu, Ni, and Mn caused by former lead mining gallery. AB - In the present study, levels of metal contamination caused by former lead mining area were figured out. For this purpose, Pb, Cd, Cu, Ni, and Mn were determined not only in sediment samples taken from different places of the mining area but also in some plants taken around the mining place. In the digestion of plant samples, dry ashing procedure was applied. Flame atomic absorption spectrophotometer (FAAS) was used in the determination of analytes of interest. All the parameters in digestion and detection procedures were optimized to obtain efficient digestion and high sensitivities for analytes. Standard addition and direct calibration methods were applied to find whether there was any matrix interference to affect the determination of analytes. Mn concentration was found to be the highest for each sample analyzed. Lead concentration was found to be between 41 and 249 mg/kg in soil/sediment samples and between 2.2 and 1003 mg/kg in plant samples. The highest contamination levels for all of the analytes with the exception of Cd were found in current sediment sample. PMID- 26837381 TI - Environmental impact of phosphogypsum stockpile in remediated Schistos waste site (Piraeus, Greece) using a combination of gamma-ray spectrometry with geographic information systems. AB - From 1979 to 1989, ten million tons of phosphogypsum, a waste by-product of the Greek phosphate fertilizer industry, was disposed into an abandoned limestone quarry in Schistos former waste site, Piraeus (Greece). The quarry has been recently closed and remediated using geomembranes and thick soil cover with vegetation. A part of the deposited phosphogypsum has been exposed due to intense rainfall episodes leading to concerns about how could potentially released radioactivity affect the surrounding environment. This study seeks to assess the environmental impact of the phosphogypsum deposited in the Schistos quarry, using laboratory-based gamma-ray spectrometry measurements and geographical information systems. Radioactivity concentrations were mapped onto spatial-data to yield a spatial-distribution of radioactivity in the area. The data indicate elevated (226)Ra concentrations in a specific area on the steep south-eastern cliff of the remediated waste site that comprises uncovered phosphogypsum and is known to be affected by local weather conditions. (226)Ra concentrations range from 162 to 629 Bq/kg, with an average activity being on the low side, compared to the global averages for phosphogypsum. Nevertheless, the low environmental risk may be minimized by remediating this area with geomembranes and thick soil cover with vegetation, a technique, which has worked successfully over the remainder of the remediated quarry. PMID- 26837382 TI - Insight into dissolved organic matter fractions in Lake Wivenhoe during and after a major flood. AB - Dissolved organic matter is an important component of biogeochemical processes in aquatic environments. Dissolved organic matter may consist of a myriad of different fractions and resultant processing pathways. In early January 2011, heavy rainfall occurred across South East Queensland, Australia causing significant catchment inflow into Lake Wivenhoe, which is the largest water supply reservoir for the city of Brisbane, Australia. The horizontal and vertical distributions of dissolved organic matter fractions in the lake during the flood period were investigated and then compared with stratified conditions with no catchment inflows. The results clearly demonstrate a large variation in dissolved organic matter fractions associated with inflow conditions compared with stratified conditions. During inflows, dissolved organic matter concentrations in the reservoir were fivefold lower than during stratified conditions. Within the dissolved organic matter fractions during inflow, the hydrophobic and humic acid fractions were almost half those recorded during the stratified period whilst low molecular weight neutrals were higher during the flood period compared to during the stratified period. Information on dissolved organic matter and the spatial and vertical variations in its constituents' concentrations across the lake can be very useful for catchment and lake management and for selecting appropriate water treatment processes. PMID- 26837383 TI - Quantitative proteomics analysis reveals glutamine deprivation activates fatty acid beta-oxidation pathway in HepG2 cells. AB - Glutamine, a multifunctional amino acid, functions in nutrient metabolism, energy balance, apoptosis, and cell proliferation. Lipid is an important nutrient and controls a broad range of physiological processes. Previous studies have demonstrated that glutamine can affect lipolysis and lipogenesis, but the effect of glutamine on the detailed lipid metabolism remains incompletely understood. Here, we applied the quantitative proteomics approach to estimate the relative abundance of proteins in HepG2 cells treated by glutamine deprivation. The results showed that there were 212 differentially abundant proteins in response to glutamine deprivation, including 150 significantly increased proteins and 62 significantly decreased proteins. Interestingly, functional classification showed that 43 differentially abundant proteins were related to lipid metabolism. Further bioinformatics analysis and western blotting validation revealed that lipid accumulation may be affected by beta-oxidation of fatty acid induced by glutamine deprivation in HepG2 cells. Together, our results may provide the potential for regulating lipid metabolism by glutamine in animal production and human nutrition. The MS data have been deposited to the ProteomeXchange Consortium with identifier PXD003387. PMID- 26837384 TI - Effects of long- and short-term management on the functional structure of meadows through species turnover and intraspecific trait variability. AB - The functional structures of communities respond to environmental changes by both species replacement (turnover) and within-species variation (intraspecific trait variability; ITV). Evidence is lacking on the relative importance of these two components, particularly in response to both short- and long-term environmental disturbance. We hypothesized that such short- and long-term perturbations would induce changes in community functional structure primarily via ITV and turnover, respectively. To test this we applied an experimental design across long-term mown and abandoned meadows, with each plot containing a further level of short term management treatments: mowing, grazing and abandonment. Within each plot, species composition and trait values [height, shoot biomass, and specific leaf area (SLA)] were recorded on up to five individuals per species. Positive covariations between the contribution of species turnover and ITV occurred for height and shoot biomass in response to both short- and long-term management, indicating that species turnover and intraspecific adjustments selected for similar trait values. Positive covariations also occurred for SLA, but only in response to long-term management. The contributions of turnover and ITV changed depending on both the trait and management trajectory. As expected, communities responded to short-term disturbances mostly through changes in intraspecific trait variability, particularly for height and biomass. Interestingly, for SLA they responded to long-term disturbances by both species turnover and intraspecific adjustments. These findings highlight the importance of both ITV and species turnover in adjusting grassland functional trait response to environmental perturbation, and show that the response is trait specific and affected by disturbance regime history. PMID- 26837385 TI - Evaluation of biochemical markers combined with uterine artery Doppler parameters in fetuses with growth restriction: a case-control study. AB - PURPOSE: Assessing the biochemical markers levels and the uterine artery Doppler (UtA) parameters in fetuses with growth restriction (FGR). METHODS: Prospective case-control study included 66 patients with diagnosis of FGR and 64 healthy pregnancies at 24-41 weeks of gestation. For both groups, maternal circulating concentrations of biochemical factors of soluble fms-like tyrosine kinase-1 (sFlt 1), soluble endoglin(sEng), adiponectin, A disintegrin and metalloproteinases (ADAM-12), pregnancy-associated plasma protein-A (PAPP-A), angiopoietin-2 (ANGI 2), vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-beta) were assayed by ELISA and UtA by Doppler were performed. ANOVA, Mann Whitney tests and Pearson correlation coefficient were applied to compare the biochemical factors, UtA Doppler and EFW Z-score between the groups. RESULTS: Concentrations of sFlt-1, sEng, PAPP-A were significantly higher in FGR than controls (p < 0.0001, p = 0.02 and p = 0.03, respectively), but concentration of ANGI-2 (p < 0.0001) was significantly lower in FGR than controls and ADAM-12 levels had a tendency to be lower in the FGR, though not statistically significant (p = 0.059). Increased sEng concentrations were correlated with abnormal UtA Doppler in FGR. CONCLUSION: Fetal growth restriction fetuses showed increased serum levels of sFlt-1, sEng and PAPP-A with levels of ANGI-2 decreased and a positive association between elevated concentrations of sEng and changing impedance of UtA Doppler were observed. PMID- 26837386 TI - Induction of labor in nulliparous women with unfavorable cervix: a comparison of Foley catheter and vaginal prostaglandin E2. AB - PURPOSE: To compare maternal and neonatal outcomes of two methods of labor induction in nulliparous women with unfavorable cervix. METHODS: A case-control study was performed on nulliparous women with a cervical Bishop score < 6, who underwent induction of labor with either extra-amniotic Foley catheter (Foley catheter study group) or vaginal tablets of prostaglandin E2 (PGE2 control group). The control group was matched for gestational age and for the indication to induce labor. RESULTS: A total of 346 nulliparous women were included. Similar rates of cesarean delivery were found in the Foley catheter and the PGE2 groups (25.4 vs. 24.2 %, respectively, p = 0.8), without differences in maternal or neonatal adverse outcomes. In the Foley catheter group, induction to delivery interval was shorter compared with the PGE2 group (25.1 vs. 36.6 h, respectively, p < 0.001), and more women delivered within 24 h (55.0 vs. 40.4 %, respectively, p = 0.01). CONCLUSION: Induction of labor with Foley catheter in nulliparous women with unfavorable cervix is associated with shorter induction to delivery interval, but with similar rates of cesarean deliveries and adverse pregnancy outcomes, as compared with vaginal tablets of PGE2. PMID- 26837387 TI - Using Kaolin in Reduction of Arsenic in Rice Grains: Effect of Different Types of Kaolin, pH and Arsenic Complex. AB - Kaolin was used as a soil amendment to study the effect of different types of kaolin, pH and arsenic complex on arsenic accumulation in rice grains from arsenic (As) contaminated soil. It was found that kaolin released soluble aluminium (Al) and silicon at a pH value of 3. As adsorption by crude kaolin was higher than by washed kaolin and treated kaolin due to the higher Al content found in crude kaolin. Furthermore, the addition of 5 % (w/w) crude kaolin in the solution of As-contaminated soil was able to reduce water-soluble As in the solution. In mesocosm experiments, As accumulation in rice grain was not found under the addition of kaolin conditions. Scanning electron microscopy with energy dispersive X-ray spectroscopy study found the crystallinity of Al-As complex in plant roots. This implies that while kaolin adsorbs As from As-contaminated soil, rice plants also simultaneously take up As and Al into their cells. This caused the decrease in As accumulation in rice grain. PMID- 26837388 TI - An illustrative review to understand and manage metal-induced artifacts in musculoskeletal MRI: a primer and updates. AB - This article reviews and explains the basic physical principles of metal-induced MRI artifacts, describes simple ways to reduce them, and presents specific reduction solutions. Artifacts include signal loss, pile-up artifacts, geometric distortion, and failure of fat suppression. Their nature and origins are reviewed and explained though schematic representations that ease the understanding. Then, optimization of simple acquisition parameters is detailed. Lastly, dedicated sequences and options specifically developed to reduce metal artifacts (VAT, SEMAC, and MAVRIC) are explained. PMID- 26837389 TI - Detection of Puccinia kuehnii Causing Sugarcane Orange Rust with a Loop-Mediated Isothermal Amplification-Based Assay. AB - Puccinia kuehnii is a fungal pathogen that causes orange rust in sugarcane, which is now prevalent in many countries. At the early stage of disease, it is almost indistinguishable from brown rust, which is caused by Puccinia melanocephala. Although several PCR assays are available to detect these diseases, the loop mediated isothermal amplification (LAMP)-based assay has been reported to be more economical and easier to perform. Under isothermal conditions, DNA is amplified with high specificity and rapidity. Moreover, visual judgment of color change without further post-amplification processing makes the method convenient. The present study was undertaken to detect P. kuehnii genomic DNA using four primers corresponding to a unique DNA sequence of P. kuehnii. The LAMP assay was found to be optimal when 8 mM MgSO4 was used and the reaction was incubated at 63 degrees C for 90 min. Positive samples showed a color change from orange to green upon SYBR Green I dye addition. Specificity of the LAMP test was checked with DNA of P. melanocephala, which showed no reaction. Sensitivity of the LAMP method was observed to be the same as real-time PCR at 0.1 ng, thus providing a rapid and more affordable option for early disease detection. PMID- 26837390 TI - Processes and changes experienced by clients during and after naturalistic good outcome therapies conducted by experienced psychotherapists. AB - OBJECTIVE: This study explores processes and changes experienced by clients during and after successful naturalistic therapy conducted by experienced psychotherapists. A taxonomy of content is built and presented, before the prevalence, range, and variation of process- and change categories are explored. METHOD: Sixteen therapies showing reliable improvement (on OQ-45) at treatment termination and having complete follow-up data up to 3-4 years post therapy were selected for this study. Processes and changes were extracted from clients' reports of important aspects during therapy and semi-structured interviews from termination and follow-up. A procedure allowing for description, organization, and quantification of this material was developed and followed. RESULTS: The totality of processes and changes (36 categories) reported by clients under and after these therapies are described. The most prevalent of these were exploration and more understanding (from session reports); relational quality and ways of thinking/more understanding (from interviews at termination); therapy process continues and situational changes (from follow-up interviews). CONCLUSIONS: Findings suggest that the therapies in this privileged sample are operating through a broad range of processes and changes, with all clients appreciating material from a large share of categories. PMID- 26837391 TI - Exploiting orientation-selective DEER: determining molecular structure in systems containing Cu(ii) centres. AB - Orientation-selective DEER (Double Electron-Electron Resonance) measurements were conducted on a series of rigid and flexible molecules containing Cu(ii) ions. A system with two rigidly held Cu(ii) ions was afforded by the protein homo-dimer of copper amine oxidase from Arthrobacter globiformis. This system provided experimental DEER data between two Cu(ii) ions with a well-defined distance and relative orientation to assess the accuracy of the methodology. Evaluation of orientation-selective DEER (os DEER) on systems with limited flexibility was probed using a series of porphyrin-based Cu(ii)-nitroxide and Cu(ii)-Cu(ii) model systems of well-defined lengths synthesized for this project. Density functional theory was employed to generate molecular models of the conformers for each porphyrin-based Cu(ii) dimer studied. Excellent agreement was found between DEER traces simulated using these computed conformers and the experimental data. The performance of different parameterised structural models in simulating the experimental DEER data was also investigated. The results of this analysis demonstrate the degree to which the DEER data define the relative orientation of the two Cu(ii) ions and highlight the need to choose a parameterised model that captures the essential features of the flexibility (rotational freedom) of the system being studied. PMID- 26837392 TI - Doctor-patient relationship. Islamic perspective. AB - The doctor-patient relationship is an intricate concept in which patients voluntarily approach a doctor and become part of a contract by which they tend to abide by doctor's instructions. Over recent decades, this relationship has changed dramatically due to privatization and commercialization of the health sector. A review of the relevant literature in the database of MEDLINE published in English between 1966 and August 2015 was performed with the following keywords: doctor-patient relationship, physician-patient relationship, ethics, and Islam. The Muslim doctor should be familiar with the Islamic teachings on the daily issues faced in his/her practice and the relationship with his/her patients. PMID- 26837393 TI - Current techniques of lamellar keratoplasty for keratoconus. AB - In recent years, there has been a considerable interest regarding the concept of lamellar keratoplasty (LK), which contributed in spreading the use of this procedure in the treatment of keratoconus. This is a new frontier in corneal surgery that minimizes trauma on the recipient patient since it works on a "closed bulb". The LK surgery, in fact, aims to selectively replace diseased corneal stroma, leaving the healthy endothelium. The main advantage of LK is to avoid major causes of failure of penetrating keratoplasty as immunological rejection, and the late mismatch in the transplanted cornea, thus increasing the life of transplantation. In the last decade, several techniques of LK have been proposed, depending on how the anterior portion of the recipient cornea is removed. This article, through a literary research reviews the various emerging techniques of anterior lamellar surgery for the management of keratoconus, analyzing their indications, visual outcomes, and rate of complications. PMID- 26837394 TI - Ki67 expression in breast cancer. Correlation with prognostic markers and clinicopathological parameters in Saudi patients. AB - OBJECTIVES: To evaluate Ki67 immunoexpression pattern in Saudi breast cancer (BC) patients and investigate any possible predictive or prognostic value for Ki67. METHODS: This is a retrospective study designed to quantitatively assess the Ki67 proliferative index (PI) in retrieved paraffin blocks of 115 Saudi BC patients diagnosed between January 2005 and March 2015 at the Department of Pathology, King Fahd Hospital, Al Madinah Al Munawarah, Kingdom of Saudi Arabia. The Ki67 PI was correlated with individual and combined immunoprofile data of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) with their clinicopathological parameters. RESULTS: Ki67 immunoreactivity was highly expressed (greater than 25% of the tumor cells were positive) in 85 (73.9%) patients. The Ki67 PI was significantly associated with poor prognostic clinicopathological parameters including old age (p less than 0.02), high tumor grade (p less than 0.01), lymph node metastasis (p less than 0.001), and Her-2/neu positivity (p less than 0.009). However, the association with ER positivity, PR positivity, tumor size, and lymphovascular invasion were not statistically significant. The Ki67 PI was significantly associated with BC molecular subtypes that were Her2/neu positive (luminal B and HER-2) subtypes compared with the Her2/neu negative (luminal A) subtype (p less than 0.04). CONCLUSION: The Ki67 PI is significantly higher in Saudi BC patients comparing with the reported literature. Ki67 PI was highest in the HER-2 and luminal-B molecular subtypes. Along with other prognostic indicators, Ki67 PI may be useful in predicting prognosis and management of Saudi BC patients. PMID- 26837395 TI - Transcutaneous bilirubin measurement in healthy Saudi term newborns. AB - OBJECTIVES: To evaluate the accuracy of transcutaneous bilirubin (TcB) measurement in healthy, jaundiced Saudi term newborns. METHODS: This prospective, cohort study was carried out from January 2009 to December 2012 on jaundiced, term infants admitted at the King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Paired TcB and total serum bilirubin (TSB) from healthy jaundiced term newborns were obtained. The correlation and the mean difference between the 2 methods were calculated, and Bhutani nomogram for prediction of TSB by TcB was used. Any bilirubin level at low and above the intermediate risk zone was considered significant. RESULTS: We obtained 665 paired TcB and TSB measurements from 665 newborns. The mean age at bilirubin measurement was 44.2 +/ 21 hour. Mean TSB was 147 +/- 45 MUmol/L, and TcB was 156 +/- 50 MUmol/L. Linear regression analysis showed a significant correlation between TcB and TSB (r: 0.84; 95% confidence interval [CI] = 0.82-0.86; p less than 0.001). The TcB tends to overestimate TSB. The mean difference between paired TcB and TSB was 17 MUmol /L with a 95% CI of 40 +/- 77 MUmol/L. The TcB was sensitive, but less specific. The TcB sensitivity was 83% and specificity was 71% to predict TSB during the first 72 hours of life for the whole study group. The positive predictive value was 63%, and negative predictive value was 87%. CONCLUSION: As found in this study, among the jaundiced healthy term Saudi newborns, TcB measurement provided accurate estimates of TSB values. The TcB measurements can be used effectively to screen newborns for significant jaundice. PMID- 26837396 TI - The role of ultrasound guidance in pediatric caudal block. AB - OBJECTIVES: To compare the time interval of the procedure, possible complications, post-operative pain levels, additional analgesics, and nurse satisfaction in ultrasonography-guided and standard caudal block applications. METHODS: This retrospective study was conducted in Celal Bayar University Hospital, Manisa, Turkey, between January and December 2014, included 78 pediatric patients. Caudal block was applied to 2 different groups; one with ultrasound guide, and the other using the standard method. RESULTS: The time interval of the procedure was significantly shorter in the standard application group compared with ultrasound-guided group (p=0.020). Wong-Baker FACES Pain Rating Scale values obtained at the 90th minute was statistically lower in the standard application group compared with ultrasound-guided group (p=0.035). No statistically significant difference was found on the other parameters between the 2 groups. The shorter time interval of the procedure at standard application group should not be considered as a distinctive mark by the pediatric anesthesiologists, because this time difference was as short as seconds. CONCLUSION: Ultrasound guidance for caudal block applications would neither increase nor decrease the success of the treatment. However, ultrasound guidance should be needed in cases where the detection of sacral anatomy is difficult, especially by palpations. PMID- 26837397 TI - Late-presenting developmental dysplasia of the hip in Jordanian males. A retrospective hospital based study. AB - OBJECTIVES: To describe the pattern of developmental dysplasia of the hip (DDH) in late presenting Jordanian male patients and identify the risk factors and associated findings. METHODS: This is a retrospective study of 1145 male patients who attended the Pediatric Orthopedic Clinic for a DDH check up. This study was carried out in the Orthopedic Section, Special Surgery Department, Faculty of Medicine, The University of Jordan, Amman, Jordan between March 2011 and October 2014. Data was collected from medical records, and x-ray measurements were evaluated. RESULTS: Of the 1145 male patients, 43 (3.75%) with 70 involved hips were diagnosed with late- presenting DDH. Being a first-born baby resulted in 41.9% increased risk for DDH. Cesarian delivery was significantly associated with an increased risk of hip dislocation (p=0.004) while normal delivery was significantly associated with acetabular dysplasia (p=0.004). No predictable risk factors were found in 44.2% patients with DDH. Bilateral cases were more common than unilateral cases: (26 [60.5%] versus 17 [39.5%]). Limited abduction was a constant finding in all dislocated hips (p less than 0.001). Associated conditions, such as club foot and congenital muscular torticollis were not observed. CONCLUSION: Cesarian section is a significant risk for dislocated hips while normal delivery is significantly associated with acetabular dysplasia. Bilateral DDH is more common than the unilateral. Club foot and torticollis were not observed in this series. PMID- 26837398 TI - Diabetes insipidus following neurosurgery at a university hospital in Western Saudi Arabia. AB - OBJECTIVES: To review the incidence, spectrum of clinical manifestation, course, risk factors, as well as treatment of diabetes insipidus (DI) following neurosurgery of the pituitary gland. METHODS: The files of 24 patients that underwent neurosurgery for sellar lesions, or tumor near the hypothalamus or pituitary gland at the Department of Neurosurgery, King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia were retrospectively reviewed between January 2011 to December 2014. A total of 24 patients were studied, and were divided into 2 groups namely; DI and non-DI. Patient characteristics were studied using descriptive statistics. The differences in proportion between the 2 groups were found out using Z-test for proportion in 2 populations. The mean differences in the hormonal abnormalities for the 2 groups were assessed using independent t test. All statistics are considered statistically significant when p less than 0.05. RESULTS: During hospitalization, 13 (54.2%) out of 24 patient that underwent neurosurgery had manifestations of DI, which was transient in 5 (38.8%) and permanent in 8 (61.2%). The DI subgroup contained higher prevalence of prolactinoma, craniopharyngioma, pre-operative panhypopituitarism, and macroadenoma in MRI imaging and transphenoidal surgery. Furthermore, urine osmolality was significantly lower in the DI group post-operatively with a significant p=0.023. It was recognized that the permanent DI documented more significant numbers than other studies. CONCLUSION: In our study group, it was recognized that permanent DI meant that our patients needed desmopressin for more than 3 months, which documented a more significant number than other studies. PMID- 26837399 TI - Correlation between obesity and emotional, social, and behavioral problems associated with physical limitation among children and adolescents in Western Saudi Arabia. AB - OBJECTIVES: To evaluate the impact of body mass index (BMI) on limitation of physical activity and the associated effect on behavioral, school, and social problems among obese children in Western Saudi Arabia. METHODS: A cross-sectional obesity survey was conducted in Jeddah, Saudi Arabia. Data were collected between August 2014 and February 2015 from 281 obese children aged between 2-18 (girls: 130, boys: 151). Participants were selected randomly to represent different economic status, level of education, and family structure. RESULTS: The mean age of participants was 10.5 years for girls and 10.6 years for boys. Higher BMI was associated with physical activity problems in walking (50.6%), running (55.8%), and exercise (44.3%), with school problems in attention (37.4%) and follow-up duties fade (31.3%), and with social problems in doing things other children could do (42.8%), playing with others (46%), and continuing play (33.4%). There was no significant relationship between BMI and emotional problems and school attendance. CONCLUSION: Higher BMI significantly increased physical limitation, problems maintaining attention in school, and social problems among obese children. However, emotional problems and school attendance did not show a significant correlation with BMI. PMID- 26837400 TI - Prevalence and risk factors of clopidogrel non-response among Saudi patients undergoing coronary angiography. AB - OBJECTIVES: To estimate the prevalence of clopidogrel non-response and identify its risk factors among Saudi patients. METHODS: This cross-sectional study was conducted at Prince Sultan Cardiac Center, Riyadh, Kingdom of Saudi Arabia between January and June 2013, to assess the degree of platelet inhibition using the VerifyNow assay (Accumetrics, San Diego, CA, USA) after receiving clopidogrel standard loading dose. Clopidogrel resistance was defined as <=15% platelet inhibition or greater than 213 P2Y12 reaction units (PRU). RESULTS: Three hundred and four patients were included in the study. The mean age was 60.3 +/- 11.4 years, and 73% were males. Clopidogrel doses were 300 mg (57%), 600 mg (27%), and 75 mg (16%). All patients used aspirin (81 mg in 94%). Approximately 66% (200/304) showed in vitro clopidogrel non-response, 54% had low platelet inhibitions, and 61% had high post-loading PRU. Using multivariate regression analysis that included all significant characteristics; only diabetes (odds ratio [OR]: 2.36, 95% confidence interval [CI]: 1.30-4.27, p=0.005) and higher preloading PRU (OR: 2.39, 95% CI: 1.40-4.11, p=0.002) remained significantly associated with higher clopidogrel non-response while myocardial infarction (OR: 0.34, 95% CI: 0.15-0.81, p=0.014) remained significantly associated with lower clopidogrel non-response. The associations of morbid obesity and diuretics use with higher clopidogrel non-response were slightly attenuated. CONCLUSION: Our findings indicate a high rate of clopidogrel in-vitro non-response among Saudi patients undergoing coronary angiography. PMID- 26837401 TI - Sleep quantity, quality, and insomnia symptoms of medical students during clinical years. Relationship with stress and academic performance. AB - OBJECTIVES: To determine sleep habits and sleep quality in medical students during their clinical years using validated measures; and to investigate associations with academic performance and psychological stress. METHODS: In this cross-sectional study, medical students (n=320) were randomly selected from a list of all enrolled clinical-year students in a Saudi medical school from 2011 2012. Students filled a questionnaire including demographic and lifestyle factors, Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Perceived Stress Scale. RESULTS: Students acquired on average, 5.8 hours of sleep each night, with an average bedtime at 01:53. Approximately 8% reported acquiring sleep during the day, and not during nighttime. Poor sleep quality was present in 30%, excessive daytime sleepiness (EDS) in 40%, and insomnia symptoms in 33% of students. Multivariable regression models revealed significant associations between stress, poor sleep quality, and EDS. Poorer academic performance and stress were associated with symptoms of insomnia. CONCLUSION: Sleep deprivation, poor sleep quality, and EDS are common among clinical years medical students. High levels of stress and the pressure of maintaining grade point averages may be influencing their quality of sleep. PMID- 26837402 TI - Prevalence and risks of habitual snoring and obstructive sleep apnea symptoms in adult dental patients. AB - OBJECTIVES: To determine the prevalence of habitual snoring and risk of obstructive sleep apnea (OSA) among dental patients and investigate factors associated with high-risk OSA. METHODS: This cross-sectional study was performed at the Department of Preventive Dental Sciences, College of Dentistry, University of Dammam, Kingdom of Saudi Arabia, between October and December 2014. A total of 200 consecutive female and male dental patients were included in this study. Subjective and objective assessments were carried out. Habitual snoring and risk of OSA were assessed using the Arabic version of the Berlin questionnaire. Two trained investigators carried out the objective measurements of anthropometric data, blood pressure, oxygen saturation, pulse rate, and clinical examination of upper-airway, and dental occlusion. RESULTS: Habitual snoring was present in 18.2% of the females and 81.8% of the males (p less than 0.05). Breathing pauses during sleep of more than once a week occurred in 9% (n=17) of the sample. Of the males, 78.3% were at high risk of OSA compared with 21.7% of the females. Multivariate analysis for risk of OSA revealed that obese patients were almost 10 times more likely to report OSA symptoms than their non-obese counterparts (odds ratio: 9.9, 95% confidence intervals: 4.4-22.1). Tongue indentations, tonsil size, and a high Epworth Sleepiness Scale score were also independent risks of OSA. CONCLUSION: Tongue indentations and tonsil grades III and IV were significantly associated with risk of OSA. This validates the important role of dentists in the recognition of the signs and symptoms of OSA. PMID- 26837403 TI - Stress, shift duty, and eating behavior among nurses in Central Saudi Arabia. AB - OBJECTIVES: To investigate the association between stress, shift work, and eating behavior among non-Saudi female nurses working in Central Saudi Arabia. METHODS: A sample of 395 non-Saudi female nurses from 2 major hospitals in Riyadh, Kingdom of Saudi Arabia participated in this cross-sectional study. The nurses completed a questionnaire from November 2013 to January 2014 that included items relating to stress and eating behavior using the Dutch Eating Behavior Questionnaire (DEBQ). The questionnaire also contained items pertaining to socio-demographic data, body mass index, shift work, and hours worked per week. RESULTS: For all eating styles, stress, and shift duty influenced the amount of food nurses consumed, but was more significant under a restrained eating style. Under this eating style, a significantly higher percentage of nurses reported eating more fast food, snacks, and binging, while fruits and vegetables were the least likely to be eaten under stress. High stressed nurses were more likely to present with abnormal restrained eating (odds ratio [OR]=1.52, p=0.004), emotional (OR=1.24; p=0.001), and external (OR=1.21; p=0.001) DEBQ scores. Working nighttime shift duty was positively associated with restrained eating (OR=1.53; p=0.029) and emotional eating (OR=1.24; p=0.001), but negatively associated with external eating (OR=0.45; p=0.001). CONCLUSION: Our findings suggest that stress and shift duty were associated with eating habits. PMID- 26837404 TI - Intestinal lymphangiectasia in children. A favorable response to dietary modifications. AB - Intestinal lymphangiectasia (IL) is a rare disease characterized by dilatation of intestinal lymphatics. It can be classified as primary or secondary according to the underlying etiology. The clinical presentations of IL are pitting edema, chylous ascites, pleural effusion, acute appendicitis, diarrhea, lymphocytopenia, malabsorption, and intestinal obstruction. The diagnosis is made by intestinal endoscopy and biopsies. Dietary modification is the mainstay in the management of IL with a variable response. Here we report 2 patients with IL in Bahrain who showed positive response to dietary modification. PMID- 26837405 TI - Surgical treatment of peripheral ulcerative keratitis and necrotizing scleritis in granulomatosis with polyangiitis. AB - The efficacy of surgical management of refractory ophthalmic complications of granulomatosis with polyangiitis (GPA), which is a sight threatening was reported. A 70-year-old man presented with a progressively worsening pain and redness in his right eye during the previous 6 months, and decreasing visual acuity that started one month earlier. He was misdiagnosed and treated as keratitis elsewhere, but the pain has not decreased. The diagnosis of necrotizing scleritis with peripheral ulcerative keratitis (PUK) in GPA was made in our department. Surgery was performed with necrotic tissue removal, combined with cryotherapy and a conjunctival flap covering surgery. The symptom was relieved after surgery, and the patient's ocular condition remained stable thereafter. This case first demonstrates limited ophthalmic GPA (such as, PUK and necrotizing scleritis) that was not sensitive or aggravated for traditional methods can be successfully treated by combined surgical interventions. PMID- 26837406 TI - Perceptions of Saudi dental students on cultural competency. AB - OBJECTIVES: To probe dental students' perceptions on their cultural competency and international student exchange programs as a way of improving cultural competency training. METHODS: A cross-sectional survey (n=460) was distributed to predoctoral students at the College of Dentistry, King Saud University, Riyadh, Kingdom of Saudi Arabia in May 2014 at the male and female university campuses. Descriptive statistics were carried out using Statistical Package for Social Sciences (p=0.05). RESULTS: It was found that 79.6% of students think that teaching them regarding cultural diversity is important. Only 41% of students thought their dental education teaches them on the importance of volunteerism and philanthropy. Most students (89.8%) think that international student exchanges can enhance their cultural competence. CONCLUSION: In this study, it was found that students believe that cultural competence is important and participation in international student exchange programs can enhance their training. PMID- 26837407 TI - Densitometric evaluation might prevent failure of knee artroplasty for aseptic loosening. An 8-year observational controlled study. AB - OBJECTIVES: To study the correlation between quantitative ultrasound (QUS) expressed as stiffness index (SI) and the risk of aseptic loosening of knee arthroplasty. METHODS: An observational retrospective controlled study was performed on 85 female patients (mean age: 73.3 years) divided into 2 groups from January 2007 to March 2015 and carried out at the Orthopedic Rehabilitation Unit, Casa di Cura Eremo, Arco, Trento, Italy. Group A included 42 patients who had undergone a revision of knee prosthesis for aseptic-loosening, and group B included 43 age-matched patients who underwent primary replacement of the knee without following aseptic loosening. Patients in both groups were evaluated for SI with Achilles - QUS system at the same side of the surgery. RESULTS: In group A, 20/42 patients (47.6%) had an SI T-score below -2.5. In group B, 14/43 (32.5%) patients had a SI T-score below -2.5. The difference between the 2 groups was statistically significant (p=0.015). CONCLUSION: Stiffness index appears to be an important predictor of aseptic loosening of the knee prosthesis. Therefore, densitometric evaluation, including SI, may be recommended before surgical knee replacement. PMID- 26837408 TI - Molecular and clinical characterization of a nonsense CDKN1C mutation in an Emirati patient with Beckwith-Wiedemann syndrome. PMID- 26837409 TI - Students' perceptions of problem based learning tutorial sessions in a system based hybrid curriculum. PMID- 26837410 TI - Thermal dewetting with a chemically heterogeneous nano-template for self assembled L1(0) FePt nanoparticle arrays. AB - A design for the fabrication of metallic nanoparticles is presented by thermal dewetting with a chemically heterogeneous nano-template. For the template, we fabricate a nanostructured polystyrene-b-polydimethylsiloxane (PS-b-PDMS) film on a Si|SiO2 substrate, followed by a thermal annealing and reactive ion etching (RIE) process. This gives a template composed of an ordered hexagonal array of SiOC hemispheres emerging in the polystyrene matrix. After the deposition of a FePt film on this template, we utilize the rapid thermal annealing (RTA) process, which provides in-plane stress, to achieve thermal dewetting and structural ordering of FePt simultaneously. Since the template is composed of different composition surfaces with periodically varied morphologies, it offers more tuning knobs to manipulate the nanostructures. We show that both the decrease in the area of the PS matrix and the increase in the strain energy relaxation transfer the dewetted pattern from the randomly distributed nanoparticles into a hexagonal periodic array of L10 FePt nanoparticles. Transmission electron microscopy with the in situ heating stage reveals the evolution of the dewetting process, and confirms that the positions of nanoparticles are aligned with those of the SiOC hemispheres. The nanoparticles formed by this template-dewetting show an average diameter and center-to-center distance of 19.30 +/- 2.09 nm and 39.85 +/- 4.80 nm, respectively. The hexagonal array of FePt nanoparticles reveals a large coercivity of 1.5 T, much larger than the nanoparticles fabricated by top-down approaches. This approach offers an efficient pathway toward self-assembled nanostructures in a wide range of material systems. PMID- 26837411 TI - How can the regulator show evidence of (no) risk selection in health insurance markets? Conceptual framework and empirical evidence. AB - If consumers have a choice of health plan, risk selection is often a serious problem (e.g., as in Germany, Israel, the Netherlands, the United States of America, and Switzerland). Risk selection may threaten the quality of care for chronically ill people, and may reduce the affordability and efficiency of healthcare. Therefore, an important question is: how can the regulator show evidence of (no) risk selection? Although this seems easy, showing such evidence is not straightforward. The novelty of this paper is two-fold. First, we provide a conceptual framework for showing evidence of risk selection in competitive health insurance markets. It is not easy to disentangle risk selection and the insurers' efficiency. We suggest two methods to measure risk selection that are not biased by the insurers' efficiency. Because these measures underestimate the true risk selection, we also provide a list of signals of selection that can be measured and that, in particular in combination, can show evidence of risk selection. It is impossible to show the absence of risk selection. Second, we empirically measure risk selection among the switchers, taking into account the insurers' efficiency. Based on 2-year administrative data on healthcare expenses and risk characteristics of nearly all individuals with basic health insurance in the Netherlands (N > 16 million) we find significant risk selection for most health insurers. This is the first publication of hard empirical evidence of risk selection in the Dutch health insurance market. PMID- 26837412 TI - Four years of early benefit assessment of new drugs in Germany: a qualitative study on methodological requirements for quality of life data. AB - BACKGROUND: Since 2011, an early benefit assessment (EBA) of new drugs constricts free price setting in Germany. According to the Pharmaceutical Market Restructuring Act (AMNOG), pharmaceutical companies are obliged to demonstrate added benefit of new drugs over comparative treatment. Benefit is usually evaluated by the Institute for Quality and Efficiency in Health Care (IQWiG). The final appraisal is made by the Federal Joint Committee, Germany's highest-ranking decision body in the health sector, triggering drug prize negotiations between companies and statutory health insurance funds. One of four evaluation criteria is quality of life (QoL). QoL outcomes have, however, only rarely been pivotal in EBAs. OBJECTIVE: This study determined methodological requirements for QoL measurement and data presentation in the EBA. DESIGN: In a qualitative content analysis, documents of all EBAs completed by 2014 were searched for the term QoL. Relevant passages of all EBAs of 2011-2013 were independently extracted and reduced to key content by two researchers. Recurring patterns were identified and verified through comparison with EBAs of 2014. RESULTS: We identified a range of requirements regarding QoL assessment, analysis, presentation, and interpretation, which go beyond official regulations. Disease-specific questionnaires are preferred and have to be validated according to certain standards and in the respective patient group. Effects must exceed the minimal important difference, which in turn must be validated in compliance with specific requirements. Often, instruments were not accepted as QoL measures, sometimes inconsistently across EBAs. Another frequent reason for non-acceptance of QoL data was that more than 30 % of randomized patients could not be analyzed due to missing data. CONCLUSIONS: Non-compliance with methodological requirements for QoL evidence impairs chances for positive benefit evaluation. PMID- 26837413 TI - Cross-dehydrogenative regioselective Csp3-Csp2 coupling of enamino-ketones followed by rearrangement: an amazing formation route to acridine-1,8-dione derivatives. AB - A new general method for the synthesis of acridine-1,8-diones through CDC coupling of enamino-ketones followed by rearrangement has been developed. This is a Cu(i) catalyzed procedure, based on the cross dehydrogenative coupling of the Csp(3)-H bond with the Csp(2)-H bond of enamino-ketones followed by rearrangement to acridine-1,8-diones in the presence of PTSA under an aerobic atmosphere. The synthetic route has been broadly applicable to a wide range of enamino-ketone derivatives derived from different benzyl amines as well as primary aliphatic amines having Calpha(sp(3))-H bonds with various cyclic, acyclic 1,3-diketones and also using DEAD. PMID- 26837415 TI - Overexpression of miR-30a in lung adenocarcinoma A549 cell line inhibits migration and invasion via targeting EYA2. AB - MicroRNAs (miRNAs) are a class of small non-coding RNAs and closely related to the pathogenesis of cancers. Increasing evidence indicates that miR-30a plays a profound role during the development of cancers. However, the functions of miR 30a in non-small-cell lung cancer (NSCLC) are still ambiguous. Here we found that miR-30a was decreased in lung adenocarcinoma A549 cells and in tissue samples from 14 patients by qRT-PCR, and also found that overexpression of miR-30a in A549 cells inhibited migration and invasion but not cell proliferation and cell cycle progression by wound-healing assay, matrigel invasion assay, MTS-based cell proliferation assay, and flow cytometry-based cell cycle analysis, respectively. We further explored the potential mechanism of miR-30a-mediated gene regulation in lung adenocarcinoma cell lines. EYA2 is a predicted target of miR-30a, and it has been found that EYA2 expression is inhibited by miR-30a in breast cancer cells. We demonstrated that EYA2 is a direct target of miR-30a by using the dual luciferase reporter assay in A549 cells and showed that EYA2 protein levels are inversely correlated with miR-30a expression in A549 and BEAS-2B cells. In addition, we also confirmed the rescue effects of EYA2 overexpression in A549 cells by cotransfection with EYA2 expression vector and miR-30a mimics. Taken together, our results demonstrate that overexpression of miR-30a in lung adenocarcinoma A549 cells can inhibit cell migration and invasion, which is partially attributed to the decrease of EYA2 expression. Our findings suggest that miR-30a may be used as a new potential target for the treatment of lung adenocarcinoma in the future. PMID- 26837414 TI - The involvement of N-methyl-D-aspartate receptor (NMDAR) subunit NR1 in the pathophysiology of schizophrenia. AB - Schizophrenia is a severe mental illness that afflicts nearly 1% of the world population. Although the exact pathophysiology of schizophrenia is unknown, the N methyl-d-aspartate receptor (NMDAR), a major glutamate receptor subtype, has received great attention. The NR1 subunit is often considered indispensable for functional NMDAR assemblies, abnormal modulation of which is found in patients with schizophrenia. In this review, we discuss how disrupted function of NR1 subunits in NMDAR leads to the progression and development of symptoms of schizophrenia-like behaviors in a variety of genetically modified mouse models. We also discuss some of the susceptible genes and shared signaling pathways among the schizophrenia, and how their mutations lead to NR1 subunits hypofunction. Finally, we suggest that the subunit-selective modulators of NR1 subunits in NMDA receptors may be promising tools for the therapy of schizophrenia. PMID- 26837417 TI - The fourth transmembrane helix is important for DRAM function. PMID- 26837416 TI - Gp120 binding with DC-SIGN induces reactivation of HIV-1 provirus via the NF kappaB signaling pathway. AB - The reactivation mechanism of latent human immunodeficiency virus type 1 (HIV-1) infection is unclear, especially in dendritic cells (DC). DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) binds with HIV 1 and other pathogens to activate the extracellular regulated protein kinase (ERK) and nuclear factor-kappa B (NF-kappaB) pathways and regulate cytokine expression. We hypothesized that DC-SIGN-induced signaling pathways may activate HIV-1 provirus. To investigate this hypothesis, we generated a model by transfecting 293T cells with a DC-SIGN expression plasmid and an HIV-1 5' long terminal repeat (LTR) reporter plasmid, and then stimulated the 293T cells with HIV-1 gp120 protein, wild-type HIV-1 or VSV-G-pNL4.3 pseudotype virus (without gp120 protein). It was found that the HIV-1 5'LTR was reactivated by HIV-1 gp120 in DC-SIGN-expressing 293T cells. Then the HIV-1 chronically infected CEM-Bru cells were transfected with DC-SIGN expression plasmid and stimulated by HIV-1 gp120 protein. It was found that early and late HIV-1 provirus replication was reactivated by the HIV-1 gp120/DC-SIGN stimulation. We then investigated the involvement of the ERK, p38 mitogen-activated protein kinases and NF-kappaB signaling pathways in HIV-1 gp120/DC-SIGN-induced activation of HIV-1 provirus by inhibiting the pathways specifically. Our results indicated that HIV-1 gp120/DC SIGN stimulation reactivates latent HIV-1 provirus via the NF-kappaB signal pathway. PMID- 26837418 TI - Grhl3 induces human epithelial tumor cell migration and invasion via downregulation of E-cadherin. AB - Grainyhead genes are involved in wound healing and developmental neural tube closure. Metastasis is a multistep process during which cancer cells disseminate from the site of primary tumors and establish secondary tumors in distant organs. The adhesion protein E-cadherin plays an essential role in metastasis. In light of the high degree of similarity between the epithelial-mesenchymal transition (EMT) occurring in wound-healing processes and the EMT occurring during the acquisition of invasiveness in skin or breast cancer, we investigated the role of the Grainyhead genes in cancer invasion. Here, we show that there is an inverse relationship between Grainyhead-like 3 (Grhl3) and E-cadherin expression in some epithelial tumor cell lines. Overexpression of Grhl3 in the E-cadherin-positive epithelial tumor cell line, characterized by less invasiveness, generated a transcriptional blockage of the E-cadherin gene and promoted cell migration and cell invasion. Conversely, Grhl3 depletion inhibited cell migration and cell invasion and was associated with a gain of E-cadherin expression. To further explore the mechanism by which Grhl3 regulated E-cadherin expression, an E cadherin promoter report analysis was performed and results showed that Grhl3 repressed E-cadherin gene expression by directly or indirectly binding to the E boxes present in the proximal E-cadherin promoter. Taken together, our findings define a major role for Grhl3 in the induction of migration and invasion by the downregulation of E-cadherin in cancer cells. PMID- 26837420 TI - Oncostatin M-induced cardiomyocyte dedifferentiation regulates the progression of diabetic cardiomyopathy through B-Raf/Mek/Erk signaling pathway. AB - It has been reported that oncostatin M (OSM) could initiate cardiomyocyte dedifferentiation both in vivo and in vitro. OSM-induced cardiomyocyte dedifferentiation might be a new target for the treatment of diabetic cardiomyopathy (DCM). This study was designed to determine the role of OSM in cardiomyocyte dedifferentiation and the progression of DCM. A mouse DCM model was established to evaluate the effects of OSM in vivo. Echocardiography was applied to determine cardiac function. Sirius red staining was used to detect fibrosis area. Transmission electron microscopy was used to evaluate mitochondria impairment. Real-time polymerase chain reaction and western blot analysis were performed to detect relative mRNA expressions and cardiomyocyte dedifferentiation related protein expressions, respectively. OSM treatment induced similar impaired cardiac function and cardiac ultrastructure impairment to those detected in DCM mice. The expressions of dedifferentiation markers of cardiomyocyte (Runx1, and alpha-SM-actin) were up-regulated in the OSM-treated mice compared with those in the control group. To further demonstrate the important role of OSM, OSM receptor knockout (Obeta(ko)) mice were used. In Obeta(ko) mice, cardiomyocytes dedifferentiation markers of c-kit, Runx1, and atrial natriuretic peptide were down-regulated, with attenuated DCM injury and abrogated OSM/B-Raf/Mek/Erk signaling pathway. In conclusion, OSM-induced cardiomyocyte dedifferentiation plays a crucial role in the progression of DCM. The mechanism of OSM-induced cardiomyocyte dedifferentiation is associated with B-Raf/Mek/Erk signaling pathway through the OSM receptor Obeta. PMID- 26837422 TI - Iron cyclopentadienone complexes derived from C2-symmetric bis-propargylic alcohols; preparation and applications to catalysis. AB - A series of complexes containing the iron-cyclopentadienone structure were prepared by cyclising bis-propargylic alcohols and their derivatives with iron pentacarbonyl. The resulting complexes were characterised and tested in the catalysis of ketone reduction and alcohol oxidation. The complexes are competent catalysts for ketone reduction and alcohol oxidations. PMID- 26837419 TI - Transcriptome sequencing and characterization of ungerminated and germinated spores of Nosema bombycis. AB - Nosema bombycis is an obligate intracellular parasitic fungus that utilizes a distinctive mechanism to infect Bombyx mori. Germination, an indispensible process through which microsporidia infect the host cells, is regarded as a key developmental turning point for microsporidia from dormant state to reproduction state. Thus, elucidating the transcriptome changes before and after germination is crucial for parasite control. However, the molecular basis of germination of microsporidia remains unknown. To investigate this germination process, the transcriptome of N. bombycis ungerminated spores and germinated spores were sequenced and analyzed. More than 60 million high-quality transcript reads were generated from these two groups using RNA-Seq technology. After assembly, 2756 and 2690 unigenes were identified, respectively, and subsequently annotated based on known proteins. After analysis of differentially expressed genes, 66 genes were identified to be differentially expressed (P <= 0.05) between these two groups. A protein phosphatase-associated gene was first identified to be significantly up-regulated as determined by RNA-Seq and immunoblot analysis, indicating that dephosphorylation might potentially contribute to microsporidia germination. The DEGs that encode proteins involved in glycometabolism, spore wall proteins and ricin B lectin of N. bombycis were also analyzed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed genes responsible for some specific biological functions and processes. The datasets generated in this study provide a basic characterization of the transcriptome changes in N. bombycis during germination. The analysis of transcriptome data and identification of certain functional genes which are robust candidate genes related to germination will help to provide a deep understanding of spore germination and invasion. PMID- 26837423 TI - Bar Coding MS(2) Spectra for Metabolite Identification. AB - Metabolite identifications are most frequently achieved in untargeted metabolomics by matching precursor mass and full, high-resolution MS(2) spectra to metabolite databases and standards. Here we considered an alternative approach for establishing metabolite identifications that does not rely on full, high resolution MS(2) spectra. First, we select mass-to-charge regions containing the most informative metabolite fragments and designate them as bins. We then translate each metabolite fragmentation pattern into a binary code by assigning 1's to bins containing fragments and 0's to bins without fragments. With 20 bins, this binary-code system is capable of distinguishing 96% of the compounds in the METLIN MS(2) library. A major advantage of the approach is that it extends untargeted metabolomics to low-resolution triple quadrupole (QqQ) instruments, which are typically less expensive and more robust than other types of mass spectrometers. We demonstrate a method of acquiring MS(2) data in which the third quadrupole of a QqQ instrument cycles over 20 wide isolation windows (coinciding with the location and width of our bins) for each precursor mass selected by the first quadrupole. Operating the QqQ instrument in this mode yields diagnostic bar codes for each precursor mass that can be matched to the bar codes of metabolite standards. Furthermore, our data suggest that using low-resolution bar codes enables QqQ instruments to make MS(2)-based identifications in untargeted metabolomics with a specificity and sensitivity that is competitive to high resolution time-of-flight technologies. PMID- 26837421 TI - MicroRNA-195a-5p inhibits mouse medullary thymic epithelial cells proliferation by directly targeting Smad7. AB - MiR-195 has been implicated in inhibiting cell proliferation in different types of tumors. Whether it contributes to the process of thymic epithelial cells (TECs) proliferation remains unclear. In this study, we found that miR-195a-5p was highly up-regulated in the TECs isolated from the aging mice. Further experiments showed that miR-195a-5p mimic transfection inhibited the proliferation of mouse medullary thymic epithelial cell line 1 (MTEC1), whereas the transfection of miR-195a-5p inhibitor in MTEC1 had the opposite effect. In addition, miR-195a-5p had no obvious effect on MTEC1 apoptosis. Furthermore, Smad7, a negative regulator of transforming growth factor beta pathway, was confirmed as a direct target of miR-195a-5p by luciferase assays. Taken together, our results indicate that miR-195a-5p inhibits MTEC1 proliferation, at least in part, via down-regulation of Smad7. PMID- 26837424 TI - Mechanisms of metal toxicity in plants. AB - Metal toxicity in plants is still a global problem for the environment, agriculture and ultimately human health. This review initially addresses the current state of the environmental/agricultural problem, and then discusses in detail the occurrence, mechanisms and relevance of toxicity of selected trace metals (Cd, Cu, Fe, Hg, Ni, and Zn). When discussing the mechanisms, special emphasis is laid on a critical review of their environmental/agricultural relevance, because even now many studies in this field of research are performed under highly artificial lab conditions. The main problems outlined in published studies are artificially high metal concentrations (which never occur even in highly polluted sites) combined with too short treatment times, as well as environmentally and agriculturally irrelevant growth conditions (e.g. constant light and submerged cultivation of seedlings). Furthermore, wherever possible an attempt is made to link the mechanisms published to date in terms of discussing which mechanisms are a direct cause of the observed disturbance of plant function and which are rather a consequence of the primary mechanisms, leading to a complicated toxicity phenotype and ultimately to diminished growth or even death of the plants. PMID- 26837426 TI - Sixty second on . . . greening the NHS. PMID- 26837427 TI - Estimating the Effect of Health Insurance on Personal Prescription Drug Importation. AB - Personal prescription drug importation occurs in the United States because of the high cost of U.S. medicines and lower cost of foreign equivalents. Importation carries a risk of exposure to counterfeit (i.e., falsified, fraudulent), adulterated, and substandard drugs. Inadequate health insurance may increase the risk of importation. We use inverse probability weighted marginal structural models and data on 87,494 individuals from the 2011-2013 National Health Interview Survey to estimate the marginal association between no health insurance and importation within U.S. subpopulations. The marginal prevalence difference [95% confidence limits] for those without (prevalence = 0.031) versus those with health insurance was 0.016 [0.011, 0.021]. The prevalence difference was higher among persons who were Hispanic, born in Latin America, Russia, or Europe, traveled to developing countries, and did not use the Internet to fill prescriptions or to find health information. Health insurance coverage may effectively reduce importation, especially among particular subpopulations. PMID- 26837428 TI - Identifying medical students at risk of underperformance from significant stressors. AB - BACKGROUND: Stress is associated with poorer academic performance but identifying vulnerable students is less clear. A series of earthquakes and disrupted learning environments created an opportunity to explore the relationships among stress, student factors, support and academic performance within a medical course. METHODS: The outcomes were deviations from expected performances on end of year written and clinical examinations. The predictors were questionnaire-based measures of connectedness/support, impact of the earthquakes, safety, depression, anxiety, stress, resilience and personality. RESULTS: The response rate was 77%. Poorer than expected performance on all examinations was associated with greater disruptions to living arrangements and fewer years in the country; on the written examination with not having a place to study; and on the clinical examination with relationship status, not having the support of others, less extroversion, and feeling less safe. There was a suggestion of a beneficial association with some markers of stress. CONCLUSION: We show that academic performance is assisted by students having a secure physical and emotional base. The students who are most vulnerable are those with fewer social networks, and those who are recent immigrants. PMID- 26837425 TI - Clinical implications from proteomic studies in neurodegenerative diseases: lessons from mitochondrial proteins. AB - Mitochondria play a key role in eukaryotic cells, being mediators of energy, biosynthetic and regulatory requirements of these cells. Emerging proteomics techniques have allowed scientists to obtain the differentially expressed proteome or the proteomic redox status in mitochondria. This has unmasked the diversity of proteins with respect to subcellular location, expression and interactions. Mitochondria have become a research 'hot spot' in subcellular proteomics, leading to identification of candidate clinical targets in neurodegenerative diseases in which mitochondria are known to play pathological roles. The extensive efforts to rapidly obtain differentially expressed proteomes and unravel the redox proteomic status in mitochondria have yielded clinical insights into the neuropathological mechanisms of disease, identification of disease early stage and evaluation of disease progression. Although current technical limitations hamper full exploitation of the mitochondrial proteome in neurosciences, future advances are predicted to provide identification of specific therapeutic targets for neurodegenerative disorders. PMID- 26837429 TI - MicroRNA profiling of the whitefly Bemisia tabaci Middle East-Aisa Minor I following the acquisition of Tomato yellow leaf curl China virus. AB - BACKGROUND: The begomoviruses are the largest and most economically important group of plant viruses exclusively vectored by whitefly (Bemisia tabaci) in a circulative, persistent manner. During this process, begomoviruses and whitefly vectors have developed close relationships and complex interactions. However, the molecular mechanisms underlying these interactions remain largely unknown, and the microRNA profiles for viruliferous and nonviruliferous whiteflies have not been studied. METHODS: Sequences of Argonaute 1(Ago1) and Dicer 1 (Dcr1) genes were cloned from B. tabaci MEAM1 cDNAs. Subsequently, deep sequencing of small RNA libraries from uninfected and Tomato yellow leaf curl China virus (TYLCCNV) infected whiteflies was performed. The conserved and novel miRNAs were identified using the release of miRBase Version 19.0 and the prediction software miRDeep2, respectively. The sequencing results of selected deregulated and novel miRNAs were further confirmed using quantitative reverse transcription-PCR. Moreover, the previously published B. tabaci MEAM1 transcriptome database and the miRNA target prediction algorithm miRanda 3.1 were utilized to predict potential targets for miRNAs. Gene Ontology (GO) analysis was also used to classify the potential enriched functional groups of their putative targets. RESULTS: Ago1 and Dcr1orthologs with conserved domains were identified from B. tabaci MEAM1. BLASTn searches and sequence analysis identified 112 and 136 conserved miRNAs from nonviruliferous and viruliferous whitefly libraries respectively, and a comparison of the conserved miRNAs of viruliferous and nonviruliferous whiteflies revealed 15 up- and 9 down-regulated conserved miRNAs. 7 novel miRNA candidates with secondary pre-miRNA hairpin structures were also identified. Potential targets of conserved and novel miRNAs were predicted using GO analysis, for the targets of up- and down-regulated miRNAs, eight and nine GO terms were significantly enriched. CONCLUSIONS: We identified Ago1 and Dcr1 orthologs from whiteflies, which indicated that miRNA-mediated silencing is present in whiteflies. Our comparative analysis of miRNAs from TYLCCNV viruliferous and nonviruliferous whiteflies revealed the relevance of deregulated miRNAs for the post-transcriptional gene regulation in these whiteflies. The potential targets of all expressed miRNAs were also predicted. These results will help to acquire a better understanding of the molecular mechanism underlying the complex interactions between begomoviruses and whiteflies. PMID- 26837430 TI - Primary alveolar soft part sarcoma of uterine corpus: a case report with immunohistochemical, ultrastructural study and review of literature. AB - BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare mesenchymal malignancy. ASPS usually occurs most commonly in the deep soft tissues of the thigh and buttock or the head and neck regions. ASPS that originate from the uterine corpus are even more rare, with only 10 previous cases reported in the English literature. CASE PRESENTATION: In our case, the alveolar features were completely lost and the tumour shows a solid, non-alveolar pattern and the nuclei have marked variation in nuclear size, and multinucleation. The correct pathological diagnosis has been made by immuno- histochemical and ultrastructural features, which rvealed overexpression of TFE3 and peculiar cytoplasmic crystalline inclusions. In this paper, an additional case of primary ASPS of uterine corpus is reported with immunohistochemical, ultrastructural study and review of literature in the effort to delineate its clinical and pathological features. In this unusual site, the diagnosis can be problematic because ASPS can mimic other primary or metastatic uterine neoplasms. CONCLUSIONS: Thus, in this unusual presentation an essential diagnostic marker is the nuclear over-expression of TFE3 as well as ultrastructural study, which reveals the presence of peculiar cytoplasmic crystalline inclusions. PMID- 26837432 TI - Improving practice with integration of patient directed activity during inpatient rehabilitation. AB - BACKGROUND: Early initiation of rehabilitation following stroke promotes better long-term outcomes than delayed onset, emphasizing the importance of inpatient therapy. However, literature indicates that following stroke individuals in inpatient rehabilitation spend the majority of their day in their bedroom and inactive. Consequently, since amount of functional activity is posited to relate to outcomes, the current rehabilitation model needs to be challenged with innovative solutions to maximize recovery. RATIONALE: In an attempt to promote greater activity and higher doses of therapy during inpatient rehabilitation, we implemented the "Patient Directed Activity Program" to facilitate specific movement and improve outcomes for patients post stroke. Our interdisciplinary activity program was conceptualized on a theoretical model for stroke recovery and principles of experience-dependent neural plasticity. MAIN FEATURES: The "Patient Directed Activity Program" includes distinct activity stations designed to increase repetition, stimulation, attention, and activity of the affected upper extremities, lower extremities, and trunk. Each task-specific activity was easily graded to achieve moderate- to high-intensity. The activity program prescribed individuals up to three additional 30-minute bouts of activities daily that were to be completed independently, and in addition to standard of care. Clinical application: After implementing this program in our facility for one year as a quality improvement project, the intervention has been delivered as an Institutional Review Board approved randomized controlled trial (Clinical Trial #NCT02446197). Challenges with people and facilities have been overcome, resulting in a feasible program that can be delivered in an inpatient setting. High satisfaction has been reported by patients and clinicians. PMID- 26837431 TI - Early home-supported discharge for patients with stroke in Portugal: a randomised controlled trial. AB - OBJECTIVE: To evaluate an early home-supported discharge service for stroke patients. DESIGN: We carried out a prospective, randomised, open-label, blinded endpoint trial (allocation ratio of 1:1) with patients assigned to either an early home-supported discharge service or usual care. SETTING: The study was undertaken in Aveiro, Portugal, between April 2009 and April 2013. SUBJECTS: We included stroke patients aged 25-85 years admitted to the stroke unit with an initial Functional Independence Measure of up to 100, who gave informed consent. INTERVENTIONS: Patients in the early home-supported discharge group began their rehabilitation intervention in the stroke unit and the early home-supported discharge team worked with them at home for a maximum of one month. Patients in the control group received usual services. MAIN MEASURES: The primary outcome measure was the Functional Independence Measure at six months after stroke. RESULTS: We randomised 190 patients of whom 34 were lost to follow-up. There were no significant differences (p > 0.5) in the average scores of Functional Independence Measure between the early home-supported discharge (69 +/-22; mean +/-SD) and the control groups (71 +/-17) measured at baseline; and between the early home-supported discharge (107 +/-20) and the control groups (107 +/-25) measured at six months. The number of individuals with a low Functional Independence Measure score (<60) in the early home-supported discharge group compared with the control group was higher at admission (34/95 vs. 26/95) and lower at follow-up (2/74 vs. 5/78). CONCLUSIONS: It was feasible to implement early home-supported discharge procedures in a Southern European setting, but we have not shown convincing differences in disability at six months. PMID- 26837434 TI - Assessment of the appropriateness of naloxone administration to patients receiving long-term opioid therapy. AB - BACKGROUND: The most dangerous adverse effect of opioids is respiratory depression. Naloxone is used to reverse this, although in patients receiving long term opioid therapy it can cause acute opioid withdrawal and opioid-refractory pain. OBJECTIVE: To determine if naloxone is appropriately administered to patients receiving long-term opioid therapy. METHODS: This retrospective case series based on chart reviews systematically identified patients over one year in a district general hospital. All patients aged 18 years or older receiving long term opioid therapy admitted to medicine, surgery or the high dependency unit who were administered naloxone during their admission were included. RESULTS: A total of 1206 patient drug administration records were reviewed. Sixteen patients receiving long-term opioid therapy were administered naloxone. Twelve of these did not have opioid-induced respiratory depression and four did not have respiratory rate and oxygen saturations documented in the medical notes. All naloxone doses administered were higher than those recommended by national guidelines for this patient group. CONCLUSIONS: No patient receiving long-term opioid therapy who was administered naloxone had evidence of respiratory depression. More thorough assessment and documentation are needed. Verbal and physical stimulation as well as oxygenation should be considered prior to naloxone administration; this should be followed by close observation, hydration, renal function tests and opioid dose review. PMID- 26837433 TI - Ghrelin receptor regulates adipose tissue inflammation in aging. AB - Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr(-/-) mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsrp(-/-) mice have reduced macrophage infiltration, M1/M2 ratio, and pro inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsrp(-/-) mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance. PMID- 26837438 TI - Description of Medication Administration by Emergency Medical Services during Mass-casualty Incidents in the United States. AB - BACKGROUND: Emergency Medical Services (EMS) preparedness and availability of essential medications are important to reduce morbidity and mortality from mass casualty incidents (MCIs). OBJECTIVES: This study describes prehospital medication administration during MCIs by different EMS service levels. METHODS: The US National EMS Public-Release Research Dataset maintained by the National Emergency Medical Services Information System (NEMSIS) was used to carry out the study. Emergency Medical Services activations coded as MCI at dispatch, or by EMS personnel, were included. The Center for Medicare and Medicaid Services (CMS) service level was used for the level of service provided. A descriptive analysis of medication administration by EMS service level was carried out. RESULTS: Among the 19,831,189 EMS activations, 53,334 activations had an MCI code, of which 26,110 activations were included. There were 8,179 (31.3%) Advanced Life Support (ALS), 5,811 (22.3%) Basic Life Support (BLS), 399 (1.5%) Air Medical Transport (AMT; fixed or rotary), and 38 (0.2%) Specialty Care Transport (SCT) activations. More than 80 different medications from 18 groups were reported. Seven thousand twenty-one activations (26.9%) had at least one medication administered. Oxygen was most common (16.3%), followed by crystalloids (6.9%), unknown (5.2%), analgesics (3.2%) mainly narcotics, antiemetics (1.5%), cardiac/vasopressors/inotropes (0.9%), bronchodilators (0.9%), sedatives (0.8%), and vasodilators/antihypertensives (0.7%). Overall, medication administration rates and frequencies of medications groups significantly varied between EMS service levels (P<.01) except for "Analgesia (other)" (P=.40) and "Pain medications (nonsteroidal anti-inflammatory drug; NSAID)" (P=.07). CONCLUSION: Medications are administered frequently in MCIs, mainly Oxygen, crystalloids, and narcotic pain medications. Emergency Medical Services systems can use the findings of this study to better prepare their stockpiles for MCIs. PMID- 26837437 TI - Evaluating mental health difficulties and associated outcomes among HIV-positive adolescents in Tanzania. AB - AIDS-related mortality among HIV-positive adolescents has risen by 50% despite the scale up of antiretroviral therapy (ART). ART maladherence likely plays a role in the increase of AIDS-related deaths among adolescents and has shown to be associated with psychosocial and mental health difficulties. Addressing the specific mental health needs of HIV-positive adolescents is critical to ending the HIV epidemic. This cross-sectional study prospectively enrolled HIV-positive adolescents (12-24 years) in Moshi, Tanzania. A structured questionnaire was administered that included questions about home, school, adherence, and measures of stigma (Berger Stigma Scale) and mental health. Mental health measures included depression (Patient Health Questionnaire-9), emotional/behavioral difficulties (Strengths and Difficulties Questionnaire), and traumatic experiences/post-traumatic stress symptoms (The University of California Los Angeles-post-traumatic stress disorder-Reaction Index). Mental health difficulties were prevalent among HIV-positive adolescents and were associated with incomplete adherence and stigma. Resources are needed to reduce HIV stigma and address mental health among HIV-positive adolescents in low-resource settings. This will improve not only mental health, but may also improve ART adherence and virologic suppression, improving overall health of the individual and reducing the risk of HIV transmission to others. PMID- 26837439 TI - Coeliac disease as a potential cause of idiopathic portal hypertension: a case report. AB - Idiopathic portal hypertension is a disorder that has various clinical features. It is mostly characterized by bleeding oesophageal varices, obvious splenomegaly, anaemia and, occasionally, jaundice and ascites. Here we described an interesting case of idiopathic portal hypertension caused by coeliac disease in a 38-year-old woman. By putting this patient on a gluten-free diet, liver function tests became normal and portal vein diameter returned to normal range. This report indicates that, in coeliac disease, repetitive stimulation by antigens along the portal vein-and immune responses to them-can result in the development of idiopathic portal hypertension. PMID- 26837441 TI - Non-neoplastic Pathology in Tumor Nephrectomy Specimens. AB - Risk factors for kidney cancers and medical kidney diseases are similar; therefore, it is not surprising that up to 25% of renal cell carcinoma patients have chronic kidney disease prior to nephrectomy and a significant number of patients with normal prenephrectomy renal function markers progress to chronic kidney disease over time. Evaluation of non-neoplastic parenchyma in tumor nephrectomy specimens can identify patients at risk for progression to chronic kidney disease, which is a critical step for early intervention and potential improvement of morbidity and mortality rates in this patient population. PMID- 26837440 TI - Autologous melanoma cell vaccine using monocyte-derived dendritic cells (NBS20/eltrapuldencel-T). AB - Targeted therapy and immunotherapy have revolutionized the treatment of advanced melanoma. Despite recent advances, lack of long-term efficacy from targeted therapy and serious immune-related toxicity are major concerns. There is unmet need for 'durable' and 'safe' treatment options for advanced melanoma. Cancer vaccine therapy in melanoma has been investigated for many years with modest clinical efficacy. More recently, dendritic cell-based vaccine products have become available for clinical use and have been the focus of investigation. CLBS20 (NBS20/eltrapuldencel-T) is a novel dendritic cell-based vaccine product that has shown promising results in early phase trials in advanced melanoma. This cancer vaccine approach could play an important role in providing a sustainable survival benefit, targeting cancer cells themselves and avoiding off-target immune-related toxicity. PMID- 26837442 TI - Nephrectomy for Non-neoplastic Kidney Diseases. AB - This review discusses the pathology of non-neoplastic kidney disease that pathologists may encounter as nephrectomy specimens. The spectrum of pediatric disease is emphasized. Histopathologic assessment of non-neoplastic nephrectomy specimens must be interpreted in the clinical context for accurate diagnosis. Although molecular pathology is not the primary focus of this review, the genetics underlying several of these diseases are also touched on. PMID- 26837443 TI - Autopsy Renal Pathology. AB - We provide an overview of assessment of the kidneys at autopsy, with special considerations for pediatric versus adult kidneys. We describe the approach to gross examination, tissue allocation when needed for additional studies of potential medical renal disease, the spectrum of congenital abnormalities of the kidneys and urinary tract, and approach to cystic diseases of the kidney. We also discuss common lesions seen at autopsy, including acute tubular injury, ischemic versus toxic contributions to this injury, interstitial nephritis, and common vascular diseases. Infections commonly involve the kidney at autopsy, and the key features and differential diagnoses are also discussed. PMID- 26837444 TI - Donor Kidney Evaluation. AB - In patients with end-stage renal disease, kidney transplantation is the best means to extend survival and offer a better quality of life. The current shortage of organs available for transplantation has led to an effort to expand the kidney donor pool, including the use of nonideal donor kidneys. Assessment of the quality of the donated kidney is essential, and would facilitate the decision to transplant a potential organ or discard it. Multiple clinical and histologic parameters have been examined to evaluate the donor kidney and relate the findings to the graft outcome, but clear-cut criteria are yet to be defined. PMID- 26837445 TI - The Basics of Renal Allograft Pathology. AB - Renal allograft biopsy provides critical information in the management of renal transplant patients, and must be analyzed in close collaboration with the clinical team. The histologic correlates of acute T-cell mediated rejection are interstitial inflammation, tubulitis, and endothelialitis; polyomavirus nephropathy is a potential mimic. Evidence of antibody-mediated rejection includes C4d deposition; morphologic acute tissue injury; and donor specific antibodies. Acute tubular injury/necrosis is a reversible cause of impaired graft function, especially in the immediate post-transplant period. Drug toxicity, recurrent disease, chronic injury, and other entities affecting both native and transplant kidneys must also be evaluated. PMID- 26837446 TI - Renal Infections. AB - This review discusses the various gross and histologic findings seen in renal infections due to bacteria, viruses, fungi, and mycobacteria. It is crucially important to separate infectious processes in the kidney from other inflammatory or neoplastic processes, as this will have a major impact on therapy. We describe the diagnostic features of renal infections with a specific focus on the differential diagnosis and other processes that may mimic infection. The topics discussed include acute bacterial pyelonephritis, chronic bacterial pyelonephritis, xanthogranulomatous pyelonephritis, malacoplakia, viral infections in the kidney, fungal pyelonephritis and mycobacterial infection of the kidney. PMID- 26837447 TI - Renal Amyloidosis. AB - Amyloidosis is an uncommon group of diseases in which soluble proteins aggregate and deposit extracellularly in tissue as insoluble fibrils, leading to tissue destruction and progressive organ dysfunction. More than 25 proteins have been identified as amyloid precursor proteins. Amyloid fibrils have a characteristic appearance on ultrastructural examination and generate anomalous colors under polarized light. Amyloidosis can be systemic or localized. The kidney is a prime site for amyloid deposition. Immunofluorescence, immunoperoxidase, and more recently laser microdissection and mass spectrometry are important tools used in the typing of renal amyloidosis. PMID- 26837448 TI - Classification Systems in Renal Pathology: Promises and Problems. AB - Kidney diseases are morphologically heterogeneous. Pathologic classifications of renal disease permit standardization of diagnosis and may identify clinical pathologic subgroups with different outcomes and/or responses to treatment. To date, classifications have been proposed for lupus nephritis, allograft rejection, IgA nephropathy, focal segmental glomerulosclerosis, antineutrophil cytoplasmic antibody -related glomerulonephritis, and diabetic glomerulosclerosis. These classifications share several limitations related to lack of specificity, reproducibility, validation, and relevance to clinical practice. They offer a standardized approach to diagnosis, however, which should facilitate communication and clinical research. PMID- 26837449 TI - Renalomics: Molecular Pathology in Kidney Biopsies. AB - In this article, various omics technologies and their applications in renal pathology (native and transplant biopsies) are reviewed and discussed. Despite significant progress and novel insights derived from these applications, extensive adoption of molecular diagnostics in renal pathology has not been accomplished. Further validation of specific applications leading to increased diagnostic precision in a clinically relevant way is ongoing. PMID- 26837450 TI - Emerging Concepts and Controversies in Renal Pathology: C4d-Negative and Arterial Lesions as Manifestations of Antibody-Mediated Transplant Rejection. AB - The consensus classification of antibody-mediated rejection (AMR) of renal allografts developed at the Sixth Banff Conference on Allograft Pathology, in 2001, identified three findings necessary for the diagnosis of active AMR: histologic evidence, antibodies against the graft, and capillary C4d deposition. Morphologic and molecular studies have noted evidence of microvascular injury, which, in the presence of donor-specific antibodies (DSAs) but the absence of C4d deposition, is associated with development of transplant glomerulopathy and graft loss. Recent studies suggest that intimal arteritis may in some cases be a manifestation of DSA-induced graft injury. These newly recognized lesions of AMR have now been incorporated into a revised Banff diagnostic schema. PMID- 26837453 TI - "Urine" the "Medulla" of the Kidney: Concentrate! PMID- 26837458 TI - Observation of the Hydrogen Migration in the Cation-Induced Fragmentation of the Pyridine Molecules. AB - The ability to selectively control chemical reactions related to biology, combustion, and catalysis has recently attracted much attention. In particular, the hydrogen atom relocation may be used to manipulate bond-breaking and new bond forming processes and may hold promise for far-reaching applications. Thus, the hydrogen atom migration preceding fragmentation of the gas-phase pyridine molecules by the H(+), H2(+), He(+), He(2+), and O(+) impact has been studied experimentally in the energy range of 5-2000 eV using collision-induced luminescence spectroscopy. Formation of the excited NH(A(3)Pi) radicals was observed among the atomic and diatomic fragments. The structure of the pyridine molecule is lacking of the NH group, therefore observation of its A(3)Pi -> X(3)Sigma(-) emission bands is an evidence of the hydrogen atom relocation prior to the cation-induced fragmentation. The NH(A(3)Pi) emission yields indicate that formation of the NH radicals depends on the type of selected projectile and can be controlled by tuning its velocity. The plausible collisional mechanisms as well as fragmentation channels for NH formation in pyridine are discussed. PMID- 26837457 TI - High-efficiency electrochemical thermal energy harvester using carbon nanotube aerogel sheet electrodes. AB - Conversion of low-grade waste heat into electricity is an important energy harvesting strategy. However, abundant heat from these low-grade thermal streams cannot be harvested readily because of the absence of efficient, inexpensive devices that can convert the waste heat into electricity. Here we fabricate carbon nanotube aerogel-based thermo-electrochemical cells, which are potentially low-cost and relatively high-efficiency materials for this application. When normalized to the cell cross-sectional area, a maximum power output of 6.6 W m( 2) is obtained for a 51 degrees C inter-electrode temperature difference, with a Carnot-relative efficiency of 3.95%. The importance of electrode purity, engineered porosity and catalytic surfaces in enhancing the thermocell performance is demonstrated. PMID- 26837456 TI - Tumour-specific CD4 T cells eradicate melanoma via indirect recognition of tumour derived antigen. AB - The importance of CD4 T cells in tumour immunity has been increasingly recognised, with recent reports describing robust CD4 T cell-dependent tumour control in mice whose immune-regulatory mechanisms have been disturbed by irradiation, chemotherapy, immunomodulatory therapy and/or constitutive immunodeficiency. Tumour control in such models has been attributed in large part to direct Major Histocompatibility Complex (MHC) class II-dependent CD4 T cell killing of tumour cells. To test whether CD4 T cells can eradicate tumours without directly killing tumour cells, we developed an animal model in which tumour-derived antigen could be presented to T-cell receptor (TCR)-transgenic CD4 T cells by host but not tumour MHC class II molecules. In I-E(+) mice bearing I E(null) tumours, naive I-E-restricted CD4 T cells proliferated locally in tumour draining lymph nodes after recognising tumour-derived antigen on migratory dendritic cells. In lymphopaenic but not immunosufficient hosts, CD4 T cells differentiated into polarised T helper type 1 (Th1) cells expressing interferon gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-2 but little IL-17, and cleared established tumours. Tumour clearance was enhanced by higher TCR affinity for tumour antigen-MHC class II and was critically dependent on IFNgamma, as demonstrated by early tumour escape in animals treated with an IFNgamma blocking antibody. Thus, CD4 T cells and IFNgamma can control tumour growth without direct T-cell killing of tumour cells, and without requiring additional adaptive immune cells such as CD8 T cells and B cells. Our results support a role for effective CD4 T cell-dependent tumour immunity against MHC class II-negative tumours. PMID- 26837459 TI - Possible shift in the ENSO-Indian monsoon rainfall relationship under future global warming. AB - EI Nino-Southern Oscillation (ENSO) and Indian monsoon rainfall are known to have an inverse relationship, which we have observed in the rainfall spectrum exhibiting a spectral dip in 3-5 y period band. It is well documented that El Nino events are known to be associated with deficit rainfall. Our analysis reveals that this spectral dip (3-5 y) is likely to shift to shorter periods (2.5 3 y) in future, suggesting a possible shift in the relationship between ENSO and monsoon rainfall. Spectral analysis of future climate projections by 20 Coupled Model Intercomparison project 5 (CMIP5) models are employed in order to corroborate our findings. Change in spectral dip speculates early occurrence of drought events in future due to multiple factors of global warming. PMID- 26837460 TI - Multiplex Strand Invasion Based Amplification (mSIBA) assay for detection of Chlamydia trachomatis and Neisseria gonorrhoeae. AB - Nucleic acid amplification tests have become a common method for diagnosis of STIs due to their improved sensitivity over immunoassays and traditional culture based methods. Isothermal nucleic acid amplification methods offer significant advantages over polymerase chain reaction (PCR) because they do not require sophisticated instruments needed for thermal cycling of PCR. We recently reported a novel isothermal nucleic acid amplification method, Strand Invasion-Based Amplification (SIBA), which exhibited high analytical sensitivity and specificity for amplification of DNA. However, because the reactions were detected using an intercalating dye, this method was only suitable for amplifying a single genomic target. Here, we report the development of multiplexed SIBA (mSIBA) that allows simultaneous detection of Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and an internal control in the same reaction tube. SIBA is compatible with probes, allowing the detection of multiple DNA targets in the same reaction tube. The IC was developed to assess the quality of the isolated DNA and the integrity of the enzyme system, as well as to test oligonucleotides. The mSIBA assay retained high analytical sensitivity and specificity for the detection of CT and NG. The development of mSIBA enables rapid screening for CT and NG within point of-care or central laboratory settings. PMID- 26837461 TI - The impact of age, HIV serostatus and seroconversion on methamphetamine use. AB - BACKGROUND: Characterizing methamphetamine use in relation to age, HIV serostatus and seroconversion is pertinent given the increasingly older age of the population with HIV and the intertwined epidemics of methamphetamine use and HIV. OBJECTIVES: Study aims were to investigate whether (i) methamphetamine use differs by age and HIV serostatus, and (ii) receiving an HIV diagnosis impacts methamphetamine use among younger and older persons with HIV. METHODS: This study examined methamphetamine use characteristics among 217 individuals with a lifetime methamphetamine dependence diagnosis who completed an in-person study assessment. RESULTS: Multivariable regressions revealed that HIV serostatus uniquely attenuates methamphetamine use, such that persons with HIV report a smaller cumulative quantity (beta = -0.16, p = 0.01) and a fewer number of days (beta = -0.18, p = 0.004) of methamphetamine use than persons without HIV. Among the HIV+ sample, all participants persisted in methamphetamine use after receiving an HIV diagnosis, with about 20% initiating use after seroconversion. Repeated measures analysis of variance indicated that density of methamphetamine use (i.e. grams per day used) was greater among the younger, relative to the older, HIV+ group (p = 0.02), and increased for both age groups following seroconversion (p < 0.001). CONCLUSION: These analyses indicate that although HIV serostatus may attenuate methamphetamine use behaviors, many people with HIV initiate, or persist in, methamphetamine use after receiving an HIV diagnosis. These findings raise the question of whether tailoring of prevention and intervention strategies might reduce the impact of methamphetamine and HIV across the age continuum. PMID- 26837462 TI - 40 Hz Auditory Steady-State Response Is a Pharmacodynamic Biomarker for Cortical NMDA Receptors. AB - Schizophrenia patients exhibit dysfunctional gamma oscillations in response to simple auditory stimuli or more complex cognitive tasks, a phenomenon explained by reduced NMDA transmission within inhibitory/excitatory cortical networks. Indeed, a simple steady-state auditory click stimulation paradigm at gamma frequency (~40 Hz) has been reproducibly shown to reduce entrainment as measured by electroencephalography (EEG) in patients. However, some investigators have reported increased phase locking factor (PLF) and power in response to 40 Hz auditory stimulus in patients. Interestingly, preclinical literature also reflects this contradiction. We investigated whether a graded deficiency in NMDA transmission can account for such disparate findings by administering subanesthetic ketamine (1-30 mg/kg, i.v.) or vehicle to conscious rats (n=12) and testing their EEG entrainment to 40 Hz click stimuli at various time points (~7 62 min after treatment). In separate cohorts, we examined in vivo NMDA channel occupancy and tissue exposure to contextualize ketamine effects. We report a robust inverse relationship between PLF and NMDA occupancy 7 min after dosing. Moreover, ketamine could produce inhibition or disinhibition of the 40 Hz response in a temporally dynamic manner. These results provide for the first time empirical data to understand how cortical NMDA transmission deficit may lead to opposite modulation of the auditory steady-state response (ASSR). Importantly, our findings posit that 40 Hz ASSR is a pharmacodynamic biomarker for cortical NMDA function that is also robustly translatable. Besides schizophrenia, such a functional biomarker may be of value to neuropsychiatric disorders like bipolar and autism spectrum where 40 Hz ASSR deficits have been documented. PMID- 26837464 TI - Steady State Vapor Bubble in Pool Boiling. AB - Boiling, a dynamic and multiscale process, has been studied for several decades; however, a comprehensive understanding of the process is still lacking. The bubble ebullition cycle, which occurs over millisecond time-span, makes it extremely challenging to study near-surface interfacial characteristics of a single bubble. Here, we create a steady-state vapor bubble that can remain stable for hours in a pool of sub-cooled water using a femtosecond laser source. The stability of the bubble allows us to measure the contact-angle and perform in situ imaging of the contact-line region and the microlayer, on hydrophilic and hydrophobic surfaces and in both degassed and regular (with dissolved air) water. The early growth stage of vapor bubble in degassed water shows a completely wetted bubble base with the microlayer, and the bubble does not depart from the surface due to reduced liquid pressure in the microlayer. Using experimental data and numerical simulations, we obtain permissible range of maximum heat transfer coefficient possible in nucleate boiling and the width of the evaporating layer in the contact-line region. This technique of creating and measuring fundamental characteristics of a stable vapor bubble will facilitate rational design of nanostructures for boiling enhancement and advance thermal management in electronics. PMID- 26837463 TI - Atomoxetine Enhances Connectivity of Prefrontal Networks in Parkinson's Disease. AB - Cognitive impairment is common in Parkinson's disease (PD), but often not improved by dopaminergic treatment. New treatment strategies targeting other neurotransmitter deficits are therefore of growing interest. Imaging the brain at rest ('task-free') provides the opportunity to examine the impact of a candidate drug on many of the brain networks that underpin cognition, while minimizing task related performance confounds. We test this approach using atomoxetine, a selective noradrenaline reuptake inhibitor that modulates the prefrontal cortical activity and can facilitate some executive functions and response inhibition. Thirty-three patients with idiopathic PD underwent task-free fMRI. Patients were scanned twice in a double-blind, placebo-controlled crossover design, following either placebo or 40-mg oral atomoxetine. Seventy-six controls were scanned once without medication to provide normative data. Seed-based correlation analyses were used to measure changes in functional connectivity, with the right inferior frontal gyrus (IFG) a critical region for executive function. Patients on placebo had reduced connectivity relative to controls from right IFG to dorsal anterior cingulate cortex and to left IFG and dorsolateral prefrontal cortex. Atomoxetine increased connectivity from the right IFG to the dorsal anterior cingulate. In addition, the atomoxetine-induced change in connectivity from right IFG to dorsolateral prefrontal cortex was proportional to the change in verbal fluency, a simple index of executive function. The results support the hypothesis that atomoxetine may restore prefrontal networks related to executive functions. We suggest that task-free imaging can support translational pharmacological studies of new drug therapies and provide evidence for engagement of the relevant neurocognitive systems. PMID- 26837466 TI - Controlled Unusual Stiffness of Mechanical Metamaterials. AB - Mechanical metamaterials that are engineered with sub-unit structures present unusual mechanical properties depending on the loading direction. Although they show promise, their practical utility has so far been somewhat limited because, to the best of our knowledge, no study about the potential of mechanical metamaterials made from sophisticatedly tailored sub-unit structures has been made. Here, we present a mechanical metamaterial whose mechanical properties can be systematically designed without changing its chemical composition or weight. We study the mechanical properties of triply periodic bicontinuous structures whose detailed sub-unit structure can be precisely fabricated using various sub micron fabrication methods. Simulation results show that the effective wave velocity of the structures along with different directions can be designed to introduce the anisotropy of stiffness by changing a volume fraction and aspect ratio. The ratio of Young's modulus to shear modulus can be increased by up to at least 100, which is a 3500% increase over that of isotropic material (2.8, acrylonitrile butadiene styrene). Furthermore, Poisson's ratio of the constituent material changes the ratio while Young's modulus does not influence it. This study presents the promising potential of mechanical metamaterials for versatile industrial and biomedical applications. PMID- 26837465 TI - Estrogen receptor-alpha is localized to neurofibrillary tangles in Alzheimer's disease. AB - The female predominance for developing Alzheimer disease (AD) suggests the involvement of gender specific factor(s) such as a reduced estrogen-estrogen receptor signaling in the pathogenesis of AD. The potential role of ERalpha in AD pathogenesis has been explored by several groups with mixed results. We revisited this issue of expression and distribution of ERalpha in AD brain using a specific ERalpha antibody. Interestingly, we found that ERalpha co-localized with neurofibrillary pathology in AD brain and further demonstrated that ERalpha interacts with tau protein in vivo. Immunoprecipitaion experiments found increased ERalpha-tau interaction in the AD cases, which may account for ERalpha being sequestered in neuronal tau pathology. Indeed, tau overexpression in M17 cells leads to interruption of estrogen signaling. Our data support the idea that sequestration of ERalpha by tau pathology underlies the loss of estrogen neuroprotection during the course of AD. PMID- 26837468 TI - Thymus Maintenance and Regeneration by Specific Molecular Factors. AB - Although the thymus plays a key role in T cell maturation in mammals, it begins to atrophy and involute at sexual maturity. The diminished thymic microenvironment is thought to contribute to reduced adaptive immune function during aging, leading to the increased likelihood of infectious diseases and cancer. Caloric restriction or ectopic expression of the pro-longevity growth factor fibroblast growth factor 21 has been reported to maintain the thymus in aging mice. Moreover, forced expression of the transcription factor FoxN1 has been shown to rejuvenate thymuses from old mice almost completely, restoring their youthful state. These results open the way for development of potential drugs to restore immune function in the elderly. PMID- 26837467 TI - Autophagy regulates Notch degradation and modulates stem cell development and neurogenesis. AB - Autophagy is a conserved, intracellular, lysosomal degradation pathway. While mechanistic aspects of this pathway are increasingly well defined, it remains unclear how autophagy modulation impacts normal physiology. It is, however, becoming clear that autophagy may play a key role in regulating developmental pathways. Here we describe for the first time how autophagy impacts stem cell differentiation by degrading Notch1. We define a novel route whereby this plasma membrane-resident receptor is degraded by autophagy, via uptake into ATG16L1 positive autophagosome-precursor vesicles. We extend our findings using a physiologically relevant mouse model with a hypomorphic mutation in Atg16L1, a crucial autophagy gene, which shows developmental retention of early-stage cells in various tissues where the differentiation of stem cells is retarded and thus reveal how modest changes in autophagy can impact stem cell fate. This may have relevance for diverse disease conditions, like Alzheimer's Disease or Crohn's Disease, associated with altered autophagy. PMID- 26837469 TI - Catalytically active tissue transglutaminase colocalises with Abeta pathology in Alzheimer's disease mouse models. AB - Alzheimer's disease (AD) is characterised by amyloid-beta (Abeta) protein deposition in the brain. Posttranslational modifications in Abeta play an important role in Abeta deposition. Tissue transglutaminase (tTG) is an enzyme involved in posttranslational cross-linking of proteins. tTG levels and activity are increased in AD brains, and tTG is associated with Abeta deposits and lesion associated astrocytes in AD cases. Furthermore, Abeta is a substrate of tTG catalysed cross-linking. To study the role of tTG in Abeta pathology, we compared tTG distribution and activity in both the APPSWE/PS1DeltaE9 and APP23 mice models with human AD. Using immunohistochemistry, we found association of both tTG and in situ active tTG with Abeta plaques and vascular Abeta, in early and late stages of Abeta deposition. In addition, tTG staining colocalised with Abeta associated reactive astrocytes. Thus, alike human AD cases, tTG was associated with Abeta depositions in these AD models. Although, distribution pattern and spatial overlay of both tTG and its activity with Abeta pathology was substantially different from human AD cases, our findings provide evidence for an early role of tTG in Abeta pathology. Yet, species differences should be taken into account when using these models to study the role of tTG in Abeta pathology. PMID- 26837470 TI - Towards a Physarum learning chip. AB - Networks of protoplasmic tubes of organism Physarum polycehpalum are macro-scale structures which optimally span multiple food sources to avoid repellents yet maximize coverage of attractants. When data are presented by configurations of attractants and behaviour of the slime mould is tuned by a range of repellents, the organism preforms computation. It maps given data configuration into a protoplasmic network. To discover physical means of programming the slime mould computers we explore conductivity of the protoplasmic tubes; proposing that the network connectivity of protoplasmic tubes shows pathway-dependent plasticity. To demonstrate this we encourage the slime mould to span a grid of electrodes and apply AC stimuli to the network. Learning and weighted connections within a grid of electrodes is produced using negative and positive voltage stimulation of the network at desired nodes; low frequency (10 Hz) sinusoidal (0.5 V peak-to-peak) voltage increases connectivity between stimulated electrodes while decreasing connectivity elsewhere, high frequency (1000 Hz) sinusoidal (2.5 V peak-to-peak) voltage stimulation decreases network connectivity between stimulated electrodes. We corroborate in a particle model. This phenomenon may be used for computation in the same way that neural networks process information and has the potential to shed light on the dynamics of learning and information processing in non-neural metazoan somatic cell networks. PMID- 26837472 TI - Duodenum-preserving pancreatic resection versus pancreaticoduodenectomy for chronic pancreatitis. AB - BACKGROUND: Surgical excision by removal of the head of the pancreas to decompress the obstructed ducts is one of the treatment options for people with symptomatic chronic pancreatitis. Surgical excision of the head of the pancreas can be performed by excision of the duodenum along with the head of the pancreas (pancreaticoduodenectomy (PD)) or without excision of the duodenum (duodenum preserving pancreatic head resection (DPPHR)). There is currently no consensus on the method of pancreatic head resection in people with chronic pancreatitis. OBJECTIVES: To assess the benefits and harms of duodenum-preserving pancreatic head resection versus pancreaticoduodenectomy in people with chronic pancreatitis for whom pancreatic resection is considered the main treatment option. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and trials registers to June 2015 to identify randomised trials. We also searched the references of included trials to identify further trials. SELECTION CRITERIA: We considered only randomised controlled trials (RCT) performed in people with chronic pancreatitis undergoing pancreatic head resection, irrespective of language, blinding, or publication status, for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently identified trials and extracted data. We calculated the risk ratio (RR), mean difference (MD), rate ratio (RaR), or hazard ratio (HR) with 95% confidence intervals (CI) based on an available-case analysis. MAIN RESULTS: Five trials including 292 participants met the inclusion criteria for the review. After exclusion of 23 participants mainly due to pancreatic cancer or because participants did not receive the planned treatment, a total of 269 participants (with symptomatic chronic pancreatitis involving the head of pancreas and requiring surgery) were randomly assigned to receive DPPHR (135 participants) or PD (134 participants). The trials did not report the American Society of Anesthesiologists (ASA) status of the participants. All the trials were single-centre trials and included people with and without obstructive jaundice and people with and without duodenal stenosis but did not report data separately for those with and without jaundice or those with and without duodenal stenosis. The surgical procedures compared in the five trials included DPPHR (Beger or Frey procedures, or wide local excision of the head of the pancreas) and PD (pylorus-preserving pancreaticoduodenectomy or Whipple procedure). The participants were followed up for various periods of time ranging from one to 15 years. The trials were at unclear or high risk of bias. The overall quality of evidence was low or very low.The differences in short-term mortality (up to 90 days after surgery) (RR 2.89, 95% CI 0.31 to 26.87; 369 participants; 5 studies; DPPHR: 2/135 (1.5%) versus PD: 0/134 (0%); very low quality evidence) or long term mortality (maximal follow-up) (HR 0.65, 95% CI 0.31 to 1.34; 229 participants; 4 studies; very low quality evidence), medium-term (three months to five years) (only a narrative summary was possible; 229 participants; 4 studies; very low quality evidence), or long-term quality of life (more than five years) (MD 8.45, 95% CI -0.27 to 17.18; 101 participants; 2 studies; low quality evidence), proportion of people with adverse events (RR 0.55, 95% CI 0.22 to 1.35; 226 participants; 4 studies; DPPHR: 23/113 (adjusted proportion 20%) versus PD: 41/113 (36.3%); very low quality evidence), number of people with adverse events (RaR 0.95, 95% CI 0.43 to 2.12; 43 participants; 1 study; DPPHR: 12/22 (54.3 events per 100 participants) versus PD: 12/21 (57.1 events per 100 participants); very low quality evidence), proportion of people employed (maximal follow-up) (RR 1.54, 95% CI 1.00 to 2.37; 189 participants; 4 studies; DPPHR: 65/98 (adjusted proportion 69.4%) versus PD: 41/91 (45.1%); low quality evidence), incidence proportion of diabetes mellitus (maximum follow-up) (RR 0.78, 95% CI 0.50 to 1.22; 269 participants; 5 studies; DPPHR: 25/135 (adjusted proportion 18.6%) versus PD: 32/134 (23.9%); very low quality evidence), and prevalence proportion of pancreatic exocrine insufficiency (maximum follow-up) (RR 0.83, 95% CI 0.68 to 1.02; 189 participants; 4 studies; DPPHR: 62/98 (adjusted proportion 62.0%) versus PD: 68/91 (74.7%); very low quality evidence) were imprecise. The length of hospital stay appeared to be lower with DPPHR compared to PD and ranged between a reduction of one day and five days in the trials (208 participants; 4 studies; low quality evidence). None of the trials reported short-term quality of life (four weeks to three months), clinically significant pancreatic fistulas, serious adverse events, time to return to normal activity, time to return to work, and pain scores using a visual analogue scale. AUTHORS' CONCLUSIONS: Low quality evidence suggested that DPPHR may result in shorter hospital stay than PD. Based on low or very low quality evidence, there is currently no evidence of any difference in the mortality, adverse events, or quality of life between DPPHR and PD. However, the results were imprecise and further RCTs are required on this topic. Future RCTs comparing DPPHR with PD should report the severity as well as the incidence of postoperative complications and their impact on patient recovery. In such trials, participant and observer blinding should be performed and the analysis should be performed on an intention-to-treat basis to decrease the bias. In addition to the short-term benefits and harms such as mortality, surgery-related complications, quality of life, length of hospital stay, return to normal activity, and return to work, future trials should consider linkage of trial participants to health databases, social databases, and mortality registers to obtain the long-term benefits and harms of the different treatments. PMID- 26837471 TI - Comprehensive safety assessment of a human inactivated diploid enterovirus 71 vaccine based on a phase III clinical trial. AB - Human enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease (HFMD). In a previous phase III trial in children, a human diploid cell-based inactivated EV71 vaccine elicited EV71 specific immune responses and protection against EV71 associated HFMD. This study aimed to assess the factors influencing the severity of adverse events observed in this previous trial. This was a randomized, double-blinded, placebo-controlled, phase III clinical trial of a human diploid vaccine carried out in 12,000 children in Guangxi Zhuang Autonomous Region, China (ClinicalTrials.gov: NCT01569581). Solicited events were recorded for 7 days and unsolicited events were reported for 28 days after each injection. Age trend analysis of adverse reaction was conducted in each treatment group. Multiple logistic regression models were built to identify factors influencing the severity of adverse reactions. Fewer solicited adverse reactions were observed in older participants within the first 7 days after vaccination (P < 0.0001), except local pain and pruritus. More severe adverse reactions were observed after the initial injection than after the booster injection. Serious cold or respiratory tract infections (RTI) were observed more often in children aged 6-36 months than in older children. Only the severity of local swelling was associated with body mass index. Children with throat discomfort before injection had a higher risk of serious cold or RTI. These results indicated that the human diploid cell-based vaccine achieved a satisfactory safety profile. PMID- 26837473 TI - Patients With Advanced Non-Small Cell Lung Cancer Requiring Inpatient Medical Oncology Consultation: Characteristics, Referral Patterns, and Outcomes. AB - BACKGROUND: Patients with advanced non-small cell lung cancer (NSCLC) occasionally are hospitalized at the time of initial medical oncology consultation. We investigated the characteristics and outcomes of this population. METHODS: With ethics approval, we performed a retrospective analysis of patients with advanced NSCLC at our institution whose initial consult occurred while hospitalized from 2007 to 2012. This was an exploratory analysis. Multivariate survival analysis was performed using Cox regression models. RESULTS: A total of 223 patients were included. Baseline demographics were as follows: median age, 65 years; 52% were female; median Charlson Comorbidity Index of 10; 69% performance status (PS) 3 to 4; 49% were current smokers; 90% had stage IV disease; and 52% had >= 5% weight loss. Only 24% received chemotherapy. Among those treated, the median time from diagnosis to chemotherapy was 43 days. Common reasons for not receiving chemotherapy included poor PS (72%) and patient choice (9%). Factors associated with receiving chemotherapy in multivariate analysis were good PS (odds ratio [OR], 9.01; 95% confidence interval [CI], 3.55 23.26; P < .001), no leukocytosis (OR, 3.56; 95% CI, 1.35-9.35; P = .01), and age < 70 years (OR, 6.80; 95% CI, 1.78-26.32; P = .005). Factors associated with shorter overall survival in multivariate analysis were not receiving chemotherapy (hazard ratio [HR], 2.11; 95% CI, 1.28-3.48; P = .003), PS 3 to 4 (HR, 1.51; 95% CI, 1.01-2.26; P = .045), leukocytosis (HR, 2.13; 95% CI, 1.44-3.13; P < .001), and thrombocytosis (HR, 1.46; 95% CI, 1.03-2.09; P = .036). CONCLUSIONS: Patients whose first consultation with medical oncologists occurs while hospitalized are an inherently sick population. Earlier diagnosis and referral would give more patients access to treatment options before a terminal functional decline. PMID- 26837474 TI - Study Design and Rationale for a Randomized, Placebo-Controlled, Double-Blind Study to Assess the Efficacy and Safety of Selumetinib in Combination With Docetaxel as Second-Line Treatment in Patients With KRAS-Mutant Advanced Non Small Cell Lung Cancer (SELECT-1). AB - BACKGROUND: Oncogenic KRAS mutations represent the largest genomically defined subset of lung cancer, and are associated with activation of the RAS/RAF/MEK/ERK pathway. There are currently no therapies specifically approved for patients with KRAS-mutant (KRASm) non-small-cell lung cancer (NSCLC), and these patients derive less clinical benefit from chemotherapy than the overall NSCLC population. In a recent phase II study, selumetinib (AZD6244, ARRY-142886), an oral, potent and selective, allosteric MEK1/2 inhibitor with a short half-life, combined with docetaxel, improved clinical outcome as second-line treatment for patients with KRASm NSCLC. This combination will be further evaluated in the phase III SELECT-1 study. PATIENTS AND METHODS: SELECT-1 (NCT01933932) is a randomized, double blind, placebo-controlled phase III study assessing the efficacy and safety of selumetinib plus docetaxel in patients with KRASm locally advanced or metastatic NSCLC, eligible for second-line treatment. The primary endpoint is progression free survival (PFS); secondary endpoints include overall survival, objective response rate, duration of response, and safety and tolerability. Approximately 634 patients will be randomized 1:1 to receive selumetinib (75 mg twice daily on a continuous oral administration schedule) in combination with docetaxel (75 mg/m(2), intravenously on day 1 of every 21-day cycle) or placebo in combination with docetaxel (same schedule), until objective disease progression. Patients may continue to receive treatment after objective disease progression if deemed appropriate by the investigator. CONCLUSIONS: If the primary endpoint of PFS is met, selumetinib plus docetaxel would be the first targeted treatment for patients with KRASm advanced NSCLC who are eligible for second-line treatment. PMID- 26837475 TI - Comorbidities Drive Outcomes for Both Malignancy-Associated and Non-Malignancy Associated Hemophagocytic Syndrome. AB - BACKGROUND: Secondary hemophagocytic syndrome (SHPS) is a syndrome that develops as a result of infection, autoimmunity, or underlying malignancy. We studied novel predictors of mortality among adults with SHPS. PATIENTS AND METHODS: SHPS were identified from the Nationwide Inpatient Sample for 2009 to 2011 using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), codes. Charlson comorbidity index (CCI) was used for comorbidity assessment, excluding malignancy. Patient- and hospital-related factors on mortality were assessed by chi-square test or analysis of variance. P values were 2 sided, and the level of significance was .05. RESULTS: A total of 276 patient hospitalizations with SHPS were identified. Forty-four had an associated malignancy, 38 (86%) of which were hematologic. Median age was 42 years (range, 18-89 years). A total of 66% (n = 182) had a CCI of 0, 13% (n = 27) had a CCI of 1, and 21% (n = 57) had a CCI of 2 or more. On bivariate analysis, inpatient mortality rate was significantly higher in malignancy-associated hemophagocytic syndrome (HPS) (odds ratio [OR], 2.07; P = .04), age >= 50 years (OR, 3.46; P < .01), CCI >= 2 (OR, 3.04; P < .01), and Medicare patients (OR, 2.32; P < .01). In multivariate analysis, CCI >= 2 remained an independent predictor of survival in the overall study cohort (OR, 3.52; 95% confidence interval, 1.51-8.18; P < .01). CONCLUSION: Malignancy-associated HPS, CCI >= 2, age > 50 years, and Medicare patients were associated with a worse in-hospital mortality. In multivariate analysis, greater comorbidity burden appeared to be the single most important predictor of mortality. This suggests that outcomes for adults with HPS are predicated by the extent of organ dysfunction at diagnosis. PMID- 26837476 TI - Multi-dimensional self-esteem and magnitude of change in the treatment of anorexia nervosa. AB - Self-esteem improvement is one of the main targets of inpatient eating disorder programmes. The present study sought to examine multi-dimensional self-esteem and magnitude of change in eating psychopathology among adults participating in a specialist inpatient treatment programme for anorexia nervosa. A standardised assessment battery, including multi-dimensional measures of eating psychopathology and self-esteem, was completed pre- and post-treatment for 60 participants (all white Scottish female, mean age=25.63 years). Statistical analyses indicated that self-esteem improved with eating psychopathology and weight over the course of treatment, but that improvements were domain-specific and small in size. Global self-esteem was not predictive of treatment outcome. Dimensions of self-esteem at baseline (Lovability and Moral Self-approval), however, were predictive of magnitude of change in dimensions of eating psychopathology (Shape and Weight Concern). Magnitude of change in Self-Control and Lovability dimensions were predictive of magnitude of change in eating psychopathology (Global, Dietary Restraint, and Shape Concern). The results of this study demonstrate that the relationship between self-esteem and eating disorder is far from straightforward, and suggest that future research and interventions should focus less exclusively on self-esteem as a uni-dimensional psychological construct. PMID- 26837477 TI - Metacognitive capacity predicts severity of trauma-related dysfunctional cognitions in adults with posttraumatic stress disorder. AB - Deficits in metacognition have been proposed as a barrier to adaptive responding to trauma. However, little is known about how different aspects of metacognitive capacity relate to responses to trauma and whether their potential link to such responses is independent of the overall level of psychopathology. To explore both issues, negative trauma-related cognitions about the self, the world, and self blame, as measured by the Posttraumatic Cognitions Inventory (PTCI), were correlated with concurrent measures of depression, posttraumatic stress disorder symptoms, and two forms of metacognition; the Metacognitions questionnaire (MCQ 30), which focuses on specific thoughts, and the Metacognition Assessment Scale Abbreviated (MAS-A) which focuses on the degree to which persons can form complex representations of self and other. Participants were 51 veterans of the wars in Iraq and Afghanistan who had a PTSD diagnosis primarily involving a combat related index trauma. Correlations revealed that being younger and more depressed were linked with greater levels of negative cognitions about self and the world. Lower levels of self-reflectivity on the MAS-A and higher levels of cognitive self-consciousness on the MCQ-30 were uniquely related to greater levels of self blame even after controlling for age, level of depression, and PTSD. Implications for research and treatment are discussed. PMID- 26837478 TI - Positive symptoms, substance use, and psychopathic traits as predictors of aggression in persons with a schizophrenia disorder. AB - It is still not clear what the unique contribution of particular psychopathological factors is in explaining aggression in schizophrenia. The current study examined whether persecutory ideations, psychopathy and substance use are associated with different measures of aggressive behavior. We expected that persecutory ideations are associated with reactive aggression, and psychopathic traits are more associated with proactive aggression of inpatients. 59 inpatients with schizophrenia were included. Persecutory ideations we assessed using the Persecutory Ideation Questionnaire (PIQ), psychopathic traits with the revised version of Psychopathic Personality Inventory (PPI-R) and substance use was assessed using the Comprehensive Assessment of Symptoms and History (CASH). In addition, aggression was measured with the Reactive and Proactive Aggression Questionnaire (RPQ), in an experimental task using the Point Subtraction Aggression Paradigm (PSAP) and on the ward using the Social Dysfunction and Aggression Scale (SDAS). Results showed that psychopathy explains most of the variance in self-reported proactive and reactive aggression. In contrast, persecutory ideations explain most of the variance in observed aggression on the ward. Results implicate that it is important to acknowledge comorbid factors in patients with schizophrenia for more precise risk assessment and appropriate treatment for aggressive patients with schizophrenia. PMID- 26837479 TI - Determining the Minimally Important Difference for the VascuQol Sumscore and Its Domains in Patients with Intermittent Claudication. AB - OBJECTIVES: The VascuQol is a questionnaire for health related quality of life (HRQL) in patients with intermittent claudication (IC), and is frequently used to evaluate treatment effects. Yet, the interpretation of change in score on a questionnaire is not always obvious. The minimally important difference (MID) represents the smallest change in score on a questionnaire that is considered relevant by patients. This study aims to determine the MID for the VascuQol sumscore and its different domains for patients with IC. METHODS: A total of 118 participants were recruited from the SUPER study, a multicenter randomized controlled trial comparing angioplasty with supervised exercise therapy for alleviation of IC due to an iliac artery stenosis or occlusion. All patients completed the VascuQol and the Short Form 36 (SF-36) questionnaires at baseline and after 12 months of follow up. Two anchor based methods for MID calculation were applied. Two anchors were used: six global rating of change questions aimed at the VascuQol sumscore and subscales and the health transition item of the SF 36, both recorded at 12 months of follow up. RESULTS: The MID for the VascuQol sumscore ranged between 1.19 and 1.66 for improvement and 0.08 and 0.41 for deterioration. For the pain domain, MID values ranged from 1.48 to 1.91 for improvement and 0.19 to 0.34 for deterioration. Finally, for the activities domain MID values ranging from 1.55 to 2.2 and from 0.12 to 0.26 for improvement and deterioration were found, respectively. Since the correlations between the anchors and the symptom, social and emotional subscales were below the threshold of 0.3, the MID was not calculated for these subscales. CONCLUSIONS: The range of MID values found in this study is an indication of the smallest change score on the VascuQol questionnaire score that is considered relevant by patients with IC. They may help to better interpret trial results and set treatment goals. PMID- 26837480 TI - Clinical Outcomes of Patients with Severe Hepatic Hereditary Hemorrhagic Telangiectasia After Banding of the Hepatic Artery and Banding/Ligation of Branches of the Hepatic Artery. AB - OBJECTIVE/BACKGROUND: To evaluate the effectiveness of double banding/ligation of hepatic arteries in treating patients with hepatic hereditary hemorrhagic telangiectasia (HHHT). METHODS: From January 2004 to December 2013, 35 patients were diagnosed with HHHT, among whom 11 woman and two men with a mean +/- SD age of 44 +/- 9 years were treated by double hepatic artery banding/ligation for cardiac insufficiency and/or portal hypertension. The outcomes were evaluated prospectively by measuring clinical manifestations, imaging features, liver and cardiac function, pulmonary arterial systolic pressure, and post-operative complications. Quality of life was evaluated with the Short Form Health Survey questionnaire. RESULTS: For each patient, the common hepatic artery and one branch of the left and/or right hepatic artery were banded, and other significantly dilated hepatic artery branches were ligated. No patient died after surgery. Clinical symptoms were improved in all patients, although ischemic cholangitis was observed in two patients and treated conservatively. Cardiac function, classified per the New York Heart Association (NYHA) cardiac functional grading, improved (NYHA III-IV vs. NYHA I-II); pulmonary arterial systolic pressure significantly decreased in all patients (48 +/- 8 mmHg vs. 24 +/- 4 mmHg; P < .001) and remained in the normal range (26 +/- 3 mmHg) at the end of follow up. The levels of gamma-glutamyl transpeptidase and alkaline phosphatase decreased in 11 patients (144 +/- 94 U/L vs. 71 +/- 34 U/L; P = .003) and 10 patients (207 +/- 71 U/L vs. 105 +/- 32 U/L; P = .001), respectively. Patients were followed up for 50 +/- 28 months (range 6-113 months); one death resulted from causes unrelated to surgery and all dimensions of quality of life improved in all surviving patients. CONCLUSIONS: This study helps to establish double hepatic artery banding/ligation as an effective therapy for selected patients with HHHT. PMID- 26837481 TI - Incidence and Risk Factors for Adverse Events Related to Image-Guided Liver Biopsy. AB - OBJECTIVE: To determine the incidence of major adverse events related to a large volume of image-guided liver biopsies performed at our institution over a 12-year period and to identify risk factors for major bleeding events. PATIENTS AND METHODS: A retrospective analysis of an internally maintained biopsy registry was performed. The analysis revealed that 6613 image-guided liver biopsies were performed in 5987 adult patients between December 7, 2001, and December 31, 2013. Liver biopsies were performed using real-time ultrasound guidance and a spring loaded biopsy device, with rare exceptions. Adverse events considered major and included in this study were hematoma, infection, pneumothorax, hemothorax, and death. Using data from the biopsy registry, we evaluated statistically significant risk factors (P<.05) for hematoma related to image-guided liver biopsy, including coagulation status, biopsy technique, and medications. RESULTS: A total of 49 acute and delayed major adverse events (0.7%) occurred after 6613 liver biopsy events. The incidence of hematoma requiring transfusion and/or angiographic intervention was 0.5% (34 of 6613). The incidence of infection was 0.1% (8 of 6613), and that of hemothorax was 0.06% (4 of 6613). No patient (0%) incurred a pneumothorax after biopsy. Three patients (0.05%) died within 30 days of liver biopsy, 1 being directly related to biopsy. Thirty-eight of 46 major adverse events (83%) presented acutely (within 24 hours). More than 2 biopsy passes, platelets 50,000/MUL or less, and female sex were statistically significant risk factors for postbiopsy hemorrhage. CONCLUSION: Image-guided liver biopsy performed by subspecialized interventionalists at a tertiary medical center is safe when the platelet count is greater than 50,000/MUL. With appreciation of specific risk factors, safety outcomes of this procedure can be optimized in both general and specialized centers. PMID- 26837483 TI - Malignant fibrous histiocytoma of the skin. A case treated with radiotherapy. PMID- 26837482 TI - Clinical and histopathologic profile of patients with primary IgA nephropathy seen in a tertiary hospital in India. AB - BACKGROUND: IgA nephropathy (IgAN) is known to have an aggressive course in Asians. There is a paucity of data regarding the Oxford classification pattern of Indian patients with IgAN. This study aims to characterize the clinical and histopathologic profile of these patients. METHODS: All patients diagnosed to have primary IgAN by kidney biopsy in the nephrology department from July 2009 to July 2014 were included in this study. All kidney biopsies were reviewed and the MEST score was assigned as per the Oxford classification. The clinical features and Oxford classification score of patients were characterized. RESULTS: Nephrotic range proteinuria (NRP) (65/103, 63.1%) with or without edema was the commonest presentation. 67.0% patients had eGFR >= 60 mL/min and 16.5% patients had eGFR < 30 mL/min. Of the 103 patients, 80 (77.7%) had M1, 10 (9.7%) had E1, 45 (43.7%) had S1 and 41 (39.8%) had T1/T2 lesions by the Oxford criteria and 11 (10.7%) patients had crescents. 62 patients had eGFR >= 30 mL/min and follow up for at least 6 months (median -17.7 (6-65.1) months) of whom 52(83.9%) had received ACEi/ARBs and 38 (61.3%) had received immunosuppression. 11/62 (17.7%) patients developed renal worsening in this period of which 7 (11.3%) developed end stage kidney disease (ESKD). CONCLUSION: Indian patients with primary IgA nephropathy have a unique profile. They commonly present with nephrotic range proteinuria. A significant proportion of these patients have normal renal function despite heavy proteinuria. Mesangial proliferative lesions are predominant with a paucity of endocapillary proliferation and crescents compared to other Asian populations. Immunosuppressive use is more common in Indian patients. PMID- 26837485 TI - Ductal Adenocarcinoma of the Pancreas. AB - Pancreatic ductal adenocarcinoma (PDAC) and its variants comprise between 80% and 90% of all tumors of the exocrine pancreas. Because of its silent course, late clinical manifestation, and rapid growth, it is considered a silent killer. Only 10% to 15% of cases are resectable and the 5-year survival rate remains lower than 5%. The differential diagnosis between PDAC and chronic pancreatitis is a challenge for pathologists. This article provides a guide for pathologic evaluation of PDAC specimens with the macroscopic and microscopic features of common PDAC and its variants and discusses the differential diagnosis and morphologic and immunophenotypical prognostic parameters. PMID- 26837484 TI - Efficacy of cyclosporine A as monotherapy in patients with psoriatic arthritis: a subgroup analysis of the SYNERGY Study. AB - BACKGROUND: The SYNERGY Study is an observational, multicenter Italian study, conducted in patients with diagnosis of psoriatic arthritis (PsA) treated from at least 3 months with cyclosporine and aimed at assessing patients' seropositivity for viral infections and efficacy and safety of cyclosporine, administered as monotherapy or in combination with other systemic drugs in the routine clinical practice. The aim of this subanalysis of the SYNERGY study was to evaluate the effects of CsA as monotherapy only in PsA over 12 months of observation. METHODS: Psoriasis was evaluated by Body Surface Area and the Psoriasis Area Severity Index (PASI). PsA was evaluated by number of swollen and tender joints, painful entheses and fingers with dactylitis, the Bath Ankylosing Spondylitis Activity Index (BASDAI) and by patients' and physicians' global assessment on a 10-point Visual Analogue Scale. RESULTS: Cyclosporine in monotherapy was effective in reducing all the measured disease parameters. The major indexes of cutaneous and spinal involvement, PASI and BASDAI were significantly reduced over the study period, as were the number of swollen and tender peripheral joints, and enthesitis and dactylitis. CONCLUSIONS: Cyclosporine in monotherapy confirmed its efficacy in cutaneous psoriasis and suggested to be effective also on PsA, reducing spinal and peripheral joints' signs and symptoms. PMID- 26837486 TI - Pancreatic Intraepithelial Neoplasia. AB - Pancreatic intraepithelial neoplasias (PanINs) are microscopic lesions of the pancreas. Traditionally viewed as a benign metaplasia of small ducts, evidence suggests that PanINs are neoplastic and that some PanINs progress to invasive ductal adenocarcinoma. The primary diagnostic challenge is distinguishing PanINs from other lesions, including invasive ductal adenocarcinoma, intraductal papillary mucinous neoplasm, and cancerization of benign ducts. PanINs are the most common of the pancreatic cancer precursor lesions, yet they remain poorly understood and are so small that they are almost clinically undetectable. Further study is required to define the role of PanINs in the carcinogenesis and early detection of pancreatic cancer. PMID- 26837487 TI - Pancreatic Cystic Tumors of Mucinous Type. AB - This article presents the clinicopathologic characteristics and differential features of pancreatic mucinous tumors. These tumors, which correspond to the most frequent cystic neoplasms, are encountered with increasing frequency. They comprise the mucinous cystic neoplasms and the intraductal papillary mucinous neoplasms. These tumors are known to progress from dysplasia to invasive carcinoma. Thus, it appears important to distinguish them from other cystic neoplasms and non-neoplastic cysts. PMID- 26837488 TI - Pancreatic Cystic Lesions of Nonmucinous Type. AB - Cystic lesions of nonmucinous type can arise within the pancreas or can develop from adjacent structures and appear to involve the pancreas. In addition, some typically solid masses can become cystic or can present as cystic lesions. Nonmucinous cysts can be neoplastic, inflammatory, reactive, or congenital. The vast majority of neoplastic nonmucinous cysts are benign. Because of the difficulty in determining the neoplastic potential of a pancreatic cyst preoperatively, many non-neoplastic cysts are resected. This article reviews the surgical pathology of nonmucinous cysts. PMID- 26837489 TI - Exocrine Pancreatic Neoplasms of Nonductal Origin: Acinar Cell Carcinoma, Pancreatoblastoma, and Solid-Pseudopapillary Neoplasm. AB - This review describes the clinicopathologic characteristics, differential diagnosis, and biologic behavior of exocrine pancreatic tumors of predominantly nonductal differentiation: acinar cell carcinoma, pancreatoblastoma, and solid pseudopapillary neoplasm. Patients usually present with a well-demarcated, large, soft, solitary mass with expansile, rather than infiltrative, growth pattern. Cystic change is common. Histologically, the tumors usually reveal at least a focal solid, cellular appearance composed of uniform, monomorphic epithelial cells. However, each type has characteristic clinicopathological features. The immunohistochemical labeling profile of pancreatoblastoma parallels the multiple lines of differentiation. These tumors are capable of producing metastases; however, their behavior is different among the types and even in the same type. Therefore, establishment of a grading system that can predict the outcome would be helpful. PMID- 26837490 TI - Conundrums and Caveats in Neuroendocrine Tumors of the Pancreas. AB - Pancreatic neuroendocrine tumors (Pan-NETs) are the second most common epithelial neoplasm of the pancreas after ductal adenocarcinoma. They can be clinically defined as functional, nonfunctional, and hereditary. This review addresses typical and atypical pathologic features of Pan-NETs, with a focus on practical issues involved in differential diagnosis, immunohistochemical work-up, intraoperative frozen section interpretation, sources of diagnostic errors, and classification. The diagnosis of a Pan-NET requires analysis of all available clinical and radiographic information and pathologic characteristics of the tumor, and it is crucial to understand the clinical impact of the pathologic interpretation. PMID- 26837491 TI - Pancreatitis, Other Inflammatory Lesions, and Pancreatic Pseudotumors. AB - The pancreas is versatile in the diversity of disorders that it can exhibit. In this article, characteristics of disorders such as chronic, autoimmune, eosinophilic, hereditary, and infectious pancreatitis are described. With regard to autoimmune pancreatitis, the role of clinical evaluation, histologic examination, and IgG4 immunohistochemistry is discussed. The role of pancreatitis in the pathogenesis of diabetes is also mentioned. Some implications of pancreatitis are highlighted, including the neoplastic predisposition caused by inflammatory lesions of the pancreas. The goal of this article is to convey an appreciation of these disorders because their recognition can benefit patients tremendously, as inflammatory lesions of the pancreas can be mass-forming, giving rise to pseudotumors, and leading to surgical resection that may otherwise be unnecessary. PMID- 26837492 TI - Cytology of the Pancreas: A Practical Review for Cytopathologists. AB - Pancreatic cytopathology plays a critical role in the management of patients with cystic and solid pancreatic masses. The frequency of pancreatic fine-needle aspiration continues to increase and general surgical pathologists and cytopathologists need to be aware of the most commonly encountered entities as well as the pitfalls associated with gastrointestinal tract contaminants in endoscopic ultrasound-guided fine-needle aspiration. This article focuses on the most commonly encountered pancreatic lesions and the importance of correlation of cytologic features with clinical, radiologic, and ancillary studies for accurate diagnosis. PMID- 26837493 TI - The Pancreas: From Sweetbread to A Diagnostic Challenge. PMID- 26837494 TI - Orientation Dependence of Electromechanical Characteristics of Defect-free InAs Nanowires. AB - Understanding the electrical properties of defect-free nanowires with different structures and their responses under deformation are essential for design and applications of nanodevices and strain engineering. In this study, defect-free zinc-blende- and wurtzite-structured InAs nanowires were grown using molecular beam epitaxy, and individual nanowires with different structures and orientations were carefully selected and their electrical properties and electromechanical responses were investigated using an electrical probing system inside a transmission electron microscope. Through our careful experimental design and detailed analyses, we uncovered several extraordinary physical phenomena, such as the electromechanical characteristics are dominated by the nanowire orientation, rather than its crystal structure. Our results provide critical insights into different responses induced by deformation of InAs with different structures, which is important for nanowire-based devices. PMID- 26837495 TI - [Research Assessment in Plastic and Reconstructive Surgery on a National Level: A 5-Years Systematic Review of Research Activity in German University Hospitals]. AB - BACKGROUND: In plastic surgery, a broad spectrum of research activity has been performed over the past decade. However, compared with other medical fields, there seems to be a lack of central coordination in the individual research areas. Also no comprehensive, periodical assessment has been undertaken to date. This study aims to provide an overview of German research activity in plastic surgery departments affiliated to medical universities. METHODS: We performed a 5 year interval (01/2010-12/2014) survey of PubMed-listed publications of plastic surgery departments in German university hospitals. For each university (n=11), statistical analyses of the following parameters were performed: distribution of research fields, number of publications, annual cumulative impact sum (IS) and impact factor (IF). RESULTS: For the above-mentioned period, a total of n=904 publications were analysed. Ranking among academic departments was as follows: number of publications: 1. Medizinische Hochschule Hannover 178 (annual average x=36/median x=34; 2. University Hospital of Erlangen 115 (x=23/x=23); 3. Bergmannsheil Bochum 90 (x=18/x=19). The annual impact sum (IS) averaged 33.51 (SD 11.088, p<0.05); separated IS: 1. Medizinische Hochschule Hannover x=74.66, x=62.22, 2. University Hospital of Erlangen x=53.24, x=50.84, 3. University Hospital RWTH Aachen x=46.12, x=44.67. The average impact factor per publication was: 1.98 (SD 0.31, p<0.05); separated IF: 1. University Hospital RWTH Aachen x=2.76, x=2.79; 2. University Hospital of Erlangen x=2.34, x=2.46; 3. Medizinische Hochschule Hannover x=2.08, x=2.05. The analysed publications were distributed as follows: 43% reviews, 20% cell biology/tissue engineering, 10% reconstruction, 27% others (including wound healing, vessel/nerve research, hand surgery, burn, aesthetics, oncology). CONCLUSION: Based on this comprehensive analysis, it seems that a periodical assessment of current research activity would be useful for the future. Data assessments should be started on European and international levels and should also be applied to other surgical and medical disciplines. PMID- 26837497 TI - Production of intracellular selenium-enriched polysaccharides from thin stillage by Cordyceps sinensis and its bioactivities. AB - BACKGROUND: Thin stillage was used as the substrate to produce intracellular selenium-enriched polysaccharides (ISPS) from Cordyceps sinensis to increase the value of agricultural coproducts. METHODS: Fermentation parameters were optimized using response surface methodology (RSM) to improve the production of ISPS. Then, the effects of ISPS on the antioxidant activities in vitro, as well as the glycosylated serum protein concentration, malondialdehyde level, and total antioxidant capacity of streptozotocin-induced diabetic rats were studied. RESULTS: The optimized conditions were as follows: sodium selenite concentration, 33.78 ug/L; incubation time, 8.24 days; and incubation temperature, 26.69 degrees C. A maximum yield of 197.35 mg/g ISPS was obtained from the validation experiments, which was quite close to the predicted maximum yield of 198.6839 mg/g. FT-IR spectra indicated that ISPS has been successfully selenylation modified with similar structure to polysaccharide of intracellular polysaccharides. The in vitro scavenging effects of 1.0 mg/mL ISPS on hydroxyl, superoxide, and 1,1-diphenyl-2-picrylhydrazyl radicals were 74.62+/-4.05, 71.45+/ 3.63, and 79.48+/-4.75%, respectively. The reducing power of ISPS was 0.45+/-0.01 (absorbance at 700 nm). Fasting blood glucose and glycosylated serum protein of group C (rats with diabetes that received drinking water with ISPS) were significantly lower than those of group B (rats with diabetes) (P<0.01) after treatment was administered for 2 and 4 weeks. Serum malonaldehyde content of group C was significantly lower than that of group B at 4 weeks (P<0.01). At 4 weeks, malonaldehyde contents in heart, liver, and kidney tissues of group C were significantly lower than those of group B; however, malonaldehyde content in pancreas tissue of group C was not significantly different. Total antioxidant capacities in liver, pancreas and kidney tissues of group C were significantly higher than those of group B, but total antioxidant capacity in heart tissue was not significantly different. Serum total antioxidant capacity was also increased compared with that of group B. CONCLUSION: The result of these experiments indicated that RSM is a promising method for the optimization of ISPS production, and the ISPS of C. sinensis can reduce blood glucose level and improve antioxidant capacity of rats with diabetes induced by streptozotocin. PMID- 26837496 TI - Supplementation of Korean Red Ginseng improves behavior deviations in animal models of autism. AB - BACKGROUND: Autism spectrum disorder (ASD) is heterogeneous neurodevelopmental disorders that primarily display social and communication impairments and restricted/repetitive behaviors. ASD prevalence has increased in recent years, yet very limited therapeutic targets and treatments are available to counteract the incapacitating disorder. Korean Red Ginseng (KRG) is a popular herbal plant in South Korea known for its wide range of therapeutic effects and nutritional benefits and has recently been gaining great scientific attention, particularly for its positive effects in the central nervous system. OBJECTIVES: Thus, in this study, we investigated the therapeutic potential of KRG in alleviating the neurobehavioral deficits found in the valproic acid (VPA)-exposed mice models of ASD. DESIGN: Starting at 21 days old (P21), VPA-exposed mice were given daily oral administrations of KRG solution (100 or 200 mg/kg) until the termination of all experiments. From P28, mice behaviors were assessed in terms of social interaction capacity (P28-29), locomotor activity (P30), repetitive behaviors (P32), short-term spatial working memory (P34), motor coordination (P36), and seizure susceptibility (P38). RESULTS: VPA-exposed mice showed sociability and social novelty preference deficits, hyperactivity, increased repetitive behavior, impaired spatial working memory, slightly affected motor coordination, and high seizure susceptibility. Remarkably, long-term KRG treatment in both dosages normalized all the ASD-related behaviors in VPA-exposed mice, except motor coordination ability. CONCLUSION: As a food and herbal supplement with various known benefits, KRG demonstrated its therapeutic potential in rescuing abnormal behaviors related to autism caused by prenatal environmental exposure to VPA. PMID- 26837498 TI - Does Surgical Repair of Moderate Ischemic Mitral Regurgitation Improve Survival? A Systematic Review. AB - Mitral regurgitation (MR) is one of the common complications in myocardial infarction (MI) patients. Almost half of the post MI patients have MR (ischemic MR)(17) which is moderate to severe (grade II-IV). Whether there is a mortality benefit of performing mitral valve repair (MVR) along with coronary artery bypass grafting (CABG) in patients with post MI moderate MR remains inconclusive. Literature search was done from PubMed, Google scholar, Ovid, and Medline databases. Studies which included post MI patients with moderate ischemic MR and reported mortality outcomes of performing CABG and MVR were chosen for the systematic review. Our preliminary literature search identified 194 studies, of which 11 studies met our inclusion criteria. Nine studies showed no survival benefit of performing simultaneous MVR and CABG. One study demonstrated survival benefit of performing CABG plus MVR only in the New York Heart Association (NYHA) class III-IV, and one study suggested survival benefit of performing CABG plus MVR as compared to CABG alone in patient with ischemic MR irrespective of preoperative NYHA functional class. Review of current literature showed mixed results in terms of improvement in functional status but failed to show any survival benefit of performing MVR along with CABG. Limitations of studies include small sample size, difference in baseline demographic variables, and short follow-up period which might influence the outcome of the study. Prospective randomized studies are required to establish clear benefit of performing MVR simultaneously with CABG. PMID- 26837499 TI - A 6-month-old boy with bilateral breast enlargement. PMID- 26837500 TI - How to interpret malaria tests. AB - There are over 300 new cases of imported paediatric malaria in the UK each year and this has been increasing over the last 20 years. Malaria in children is particularly difficult to diagnose because the initial presenting features are subtler than in adults and do not display the classical presenting features. However, they are also more likely to deteriorate rapidly and to develop severe malaria. The 'gold standard' for ruling out the diagnosis of malaria if clinically suspected is three negative thin and thick blood films, which require serial phlebotomy and the availability of trained technicians. There are now a range of other tests, including rapid diagnostic tests and PCR, as well as clinical features that make the diagnosis more or less likely. We explore the different tests available and whether these might replace the three negative blood films currently needed. We also look at whether we are able to use clinical features to aid the tests used for a diagnosis of imported malaria. PMID- 26837501 TI - Fifteen-minute consultation: Medically unexplained symptoms. AB - Medically unexplained symptoms are common and not always easy to manage. A wide range of symptoms may be presented and anxiety in the child, family and paediatrician about the possibility of a missed serious organic diagnosis may hamper effective management. Evidence-based approaches to a number of different presenting problems share a number of components. A model for assessment and management based on clinical experience and this evidence base is described. PMID- 26837503 TI - Changes in symptom intensity and emotion valence during the process of assimilation of a problematic experience: A quantitative study of a good outcome case of cognitive-behavioral therapy. AB - The assimilation model describes the change process in psychotherapy. In this study we analyzed the relation of assimilation with changes in symptom intensity, measured session by session, and changes in emotional valence, measured for each emotional episode, in the case of a 33-year-old woman treated for depression with cognitive-behavioral therapy. Results showed the theoretically expected negative relation between assimilation of the client's main concerns and symptom intensity, and the relation between assimilation levels and emotional valence corresponded closely to the assimilation model's theoretical feelings curve. The results show how emotions work as markers of the client's current assimilation level, which could help the therapist adjust the intervention, moment by moment, to the client's needs. PMID- 26837502 TI - Rapid detection of germline mutations for hereditary gastrointestinal polyposis/cancers using HaloPlex target enrichment and high-throughput sequencing technologies. AB - Genetic testing for hereditary colorectal polyposis/cancers has become increasingly important. Therefore, the development of a timesaving diagnostic platform is indispensable for clinical practice. We designed and validated target enrichment sequencing for 20 genes implicated in familial gastrointestinal polyposis/cancers in 32 cases with previously confirmed mutations using the HaloPlex enrichment system and MiSeq. We demonstrated that HaloPlex captured the targeted regions with a high efficiency (99.66 % for covered target regions, and 99.998 % for breadth of coverage), and MiSeq achieved a high sequencing accuracy (98.6 % for the concordant rate with SNP arrays). Using this approach, we correctly identified 33/33 (100 %) confirmed alterations including SNV, small INDELs and large deletions, and insertions in APC, BMPR1A, EPCAM, MLH1, MSH2, MSH6, PMS2, and SKT11. Our approach yielded the sequences of 20 target genes in a single experiment, and correctly identified all previously known mutations. Our results indicate that our approach successfully detected a wide range of genetic variations in a short turnaround time and with a small sample size for the rapid screening of known causative gene mutations of inherited colon cancer, such as familial adenomatous polyposis, Lynch syndrome, Peutz-Jeghers syndrome, and Juvenile polyposis syndrome. PMID- 26837504 TI - Comparison of Chlorella vulgaris and cyanobacterial biomass: cultivation in urban wastewater and methane production. AB - Anaerobic digestion of microalgae is hampered by its complex cell wall. Against this background, cyanobacteria cell walls render this biomass as an ideal substrate for overcoming this drawback. The aim of the present study was to compare the growth of two cyanobacteria (Aphanizomenon ovalisporum and Anabaena planctonica) and a microalga (Chlorella vulgaris) in urban wastewater when varying the temperature (22, 27 and 32 degrees C). Cyanobacterial optimal growth for both strains was attained at 22 degrees C, while C. vulgaris did not show remarkable differences among temperatures. For all the microorganisms, ammonium removal was higher than phosphate. Biomass collected was subjected to anaerobic digestion. Methane yield of C. vulgaris was 184.8 mL CH4 g COD in(-1) while with A. ovalisporum and A. planctonica the methane production was 1.2- and 1.4-fold higher. This study showed that cyanobacteria growth rates could be comparable to microalgae while presenting the additional benefit of an increased anaerobic digestibility. PMID- 26837505 TI - Periocular necrotising fasciitis: a multicentre case series. AB - INTRODUCTION: Necrotising fasciitis (NF) is a severe infection of deep subcutaneous soft tissues with high morbidity and mortality. Periocular necrotising fasciitis (PONF) is a very rare condition with many unanswered questions about the presentation and management. We present a retrospective case series of patients with PONF from three centres in Australia and two in the UK to investigate the clinical and microbiological characteristics and outcomes and report on patients treated with antibiotics alone. RESULTS: Twenty-nine patients (20 men; 69%) with PONF were identified and followed up for between 2 months and 10 years (median 57, mean 52.6 months) between 1990 and 2013. Conditions associated with chronic immunocompromise were present in 16/29 (55%). Twenty-one (75%) recalled minor periocular trauma or an infected lesion, two having been assaulted by the same assailant. Systemic shock occurred in 6/29 (21%) patients and 1 died. Group A, beta-haemolytic Streptococcus was the most common bacterium identified (25/29, 86%). Intravenous antibiotics were used in all patients, and up to five tissue debridements were required to control the disease in 23/29 (74%); reconstructive surgery was required in 12/29 (41%) patients. One patient died from the disease and visual loss occurred in four eyes of four patients (14%). CONCLUSIONS: PONF has a better prognosis than disease elsewhere in the body, but is still associated with significant risk of visual loss and a small risk of death. Intravenous antibiotic treatment with cautious observation may be reasonable in selected patients with a low threshold for debridement. PMID- 26837506 TI - Optical coherence tomography angiography characteristics of polypoidal choroidal vasculopathy. AB - PURPOSE: To analyse the morphological characteristics of polypoidal choroidal vasculopathy (PCV) on optical coherence tomography angiography (OCT-A). METHODS: Prospective study with consecutive patients affected with PCV were included. All patients underwent a complete ophthalmological examination including fundus photography, fluorescein angiography, indocyanine green angiography, spectral domain OCT and OCT-A. RESULTS: Twelve eyes of 12 patients (mean age 72.6+/-10.5 years; 4 men and 8 women) were included for analysis. In all eyes (12/12) the segmentation of the choriocapillaris layer on OCT-A revealed the branching vascular network (BVN) as a hyperflow lesion. OCT-A segmentation of the choriocapillaris layer in correspondence of the polypoidal lesion showed in 3/12 eyes (25%) a hyperflow round structure, surrounded by a hypointense halo, and in 9/12 eyes (75%) a hypoflow round structure. CONCLUSIONS: The OCT-A is a non invasive imaging modality allowing the visualisation of different structures in PCV. The BVN is constantly clearly detected. The hypoflow round structure appearance of the polyp in OCT-A, is probably due to an unusual blood flow inside the polypoidal lesions, contrasting with the BVN. Further improvement in OCT-A knowledge will provide information on the specificity of the different intensity characteristics in PCV. PMID- 26837507 TI - Preliminary outcome of hemi-Descemet membrane endothelial keratoplasty for Fuchs endothelial dystrophy. AB - BACKGROUND/AIMS: To evaluate the clinical outcome of a full-diameter, untrephined, semicircular Descemet graft in a consecutive series of Descemet membrane endothelial keratoplasty (hemi-DMEK), potentially allowing the harvesting of two grafts from a single donor corneoscleral rim. METHODS: Interventional case series of 10 eyes of 10 patients with Fuchs endothelial dystrophy. Best corrected visual acuity (BCVA), endothelial cell density (ECD) and central corneal thickness (CCT) were evaluated up to 6 months postoperatively, and intraoperative and postoperative complications were recorded. RESULTS: Hemi-DMEK was successful in 9 out of 10 eyes; one eye showed persistent graft detachment despite rebubbling and underwent a secondary DMEK. BCVA improved in all successful hemi-DMEK eyes: at 6 months 100% of eyes (n=7) reached >=20/40 (>=0.5), 86% (n=6) >=20/25 (>=0.8), 29% (n=2) >=20/20 (>=1.0) and 14% (n=1) reached 20/17 (>=1.2). Two eyes were excluded from visual analysis due to low visual potential. Preoperative donor ECD declined from 2744 (+/-181) cells/mm2 to 940 (+/-380) cells/mm2 centrally at 6 months postoperatively (n=9), with (donor and/or host) endothelial cell redistribution over bare stromal areas adjacent to the graft. Average CCT decreased from 745 (+/-153) um preoperatively to 520 (+/-37) um at 6 months. Four eyes required rebubbling for visually significant graft detachment. No other complications occurred throughout the study period. CONCLUSIONS: Hemi-DMEK may give visual outcomes similar to those in conventional DMEK. If ECD decrease and graft detachment rate would prove acceptable in larger series, hemi-DMEK could have the potential to double the availability of donor tissue for endothelial keratoplasty. PMID- 26837509 TI - Tonsillectomy 30 years after Paradise: implosion of arguments. PMID- 26837508 TI - How can periorbital oedema and ecchymose be reduced in rhinoplasty? AB - Oedema and ecchymose are frequent morbidities of septorhinoplasty, a facial surgical procedure for reforming the shape and functions of the nose. Periorbital oedema (PO) and periorbital ecchymose (PE) are normal occurrences, but are undesirable for patients undergoing the procedure for aesthetic purposes. The present study examined 65 patients who underwent open technique septorhinoplasty for aesthetic and functional complaints. Patients were divided into two groups: Group 1 patients underwent lateral osteotomy following tip plasty, at the end of the surgical operation; Group 2 patients underwent lateral osteotomy before tip plasty, at the beginning of the surgical operation. Patients were followed on the postoperative first, third and seventh days. PO and PE values of patients were scored from 0 to 4. The plastering time (Pt) was significantly shorter for Group I than Group II (p < 0.05). The total surgical time (T) showed no significant difference (p > 0.05). The PO value at the first, third and seventh days was significantly smaller for Group I than Group II (p < 0.05). The PE value at the first, third and seventh days was also significantly smaller for Group I than Group II (p < 0.05). The obtained data indicate that performing a lateral osteotomy in the final stages of surgery, and subsequently applying a nasal plaster and splint as rapidly as possible, decreases PO and PE in the postoperative period. PMID- 26837510 TI - [The Apophysis--underrated in theory and practice]. PMID- 26837511 TI - [Apophyseal Avulsions of the Hip Region in Adolescents]. AB - BACKGROUND: In daily practice apophyseal avulsions of sportive adolescents are frequently being diagnosed with a time delay and treated heterogeneously. GOAL: Using the most actual literature and the own experience the current diagnostic and therapeutic strategies are put into perspective with regards of the needs of the adolescent athlete. MATERIAL AND METHODS: The apophyseal lesions of the hip area in adolescence are separated in those at the pelvis and those at the proximal femur. They are reviewed according to its frequency and relevance using the most updated literature. The treatment methods reported focus on the degree of dislocation and level of sports activity. RESULTS: The most frequent apophyseal avulsion of the pelvis is the avulsion of the tuber ischiadicum, followed by the inferior anterior iliac spine the superior anterior iliac spine and the apophysis of the ilium. The most affected structure at the proximal femur is the lesser trochanter, lesions of the greater trochanter are rare. The cause of injury is a specific acute contracture of the muscle inserting at the affected apophysis during different sporting activities. The treatment of pelvic apophyseal injuries is surgical only in cases with considerable fragment dislocation and in high level athletes. At the femoral side the patients are treated almost always conservatively. DISCUSSION: Despite of modern and efficient osteosynthetic techniques the treatment of avulsion lesions of the hip region is mainly conservative, even in athletes. By applying consequent diagnostic and therapeutic principles the development of pseudarthroses and heteropic ossifications can be minimised. PMID- 26837512 TI - [Contamination of workwear in medical doctors and nursing stuff]. AB - BACKGROUND: The hands of medical stuff are the most important vectors for the transmission of pathogens in the hospital. Furthermore a "bare below the elbows dress code" has been introduced in Great Britain. OBJECTIVES: Aim of this study was to investigate whether workwear contamination of the medical stuff by pathogens is similar to the contamination of their hands and whether wearing workwear is associated with increased transmission risk. MATERIAL AND METHODS: In total 54 swabs were collected from nursing stuff, medical doctors, patients and hospital work material. RESULTS: Patients had a statistically significant more dense colonization with bacteria (median = 73 colony-forming units (CFU)), than the sleeves of the doctor's coat (median = 36 CFU, p = 0,005), followed by workwear of the nursing stuff at the end of a shift (median = 23 CFU, p < 0,001) and the hospital work material (median = 15 CFU, p < 0,001). Isolated pathogens were coagulase-negative staphylococci, Staphylococcus aureus, Enterobacter cloacae and Acinetobacter species. CONCLUSIONS: Contaminated work wear presents a relevant risk for the transmission of pathogens. A "bare below the elbow dress code" or the daily change of the doctor's coat appear both to represent reasonable measures to reduce the transmission risk of pathogens in hospitals. PMID- 26837513 TI - [The intraarticular osteoid osteoma : A diagnostic and therapeutic challenge]. AB - Intra- and, respectively, periarticular osteoid osteoma are accompanied by sympathical arthritis which itself can irreversibly destroy the cartilage of the joint. In contrast to other locations, intra- and periarticular osteoid osteoma are rare. Reactive and symptomatic accompanying arthritis may lead to irreversible cartilage destruction especially in chronic courses. Therefore early diagnosis and therapy is crucial. We present a case report and discuss these rare tumors by reviewing the literature. PMID- 26837514 TI - Cathepsin G-mediated proteolytic degradation of MHC class I molecules to facilitate immune detection of human glioblastoma cells. AB - To mount an adaptive immune response, MHC I molecules present antigenic peptides to CTLs. Transcriptional reduction of MHC I molecules is a strategy of immune evasion, which impairs the detection of infected or tumorous cells by CTLs. Natural killer (NK) cells, on the other hand, eliminate target cells specifically in the absence of MHC I. Consequently, infected or tumorous cells partly retain their MHC I at the cell surface to avoid NK recognition. However, it remains unclear which protease degrades MHC I molecules and how these cells maintain a limited set of MHC I at the cell surface. Here, we demonstrate that cathepsin G (CatG), a serine protease, found in the endocytic compartment of APCs and, to a lesser extent, CatD and CatS proteolytically degrade MHC I molecules. Inhibition of CatG boosted MHC I expression at the cell surface of primary human immune cells. In contrast, human glioblastoma cells do not harbor active CatG and might have lost the ability to proteolytically degrade MHC I during tumorigenesis to avoid NK-mediated killing. Overexpression of CatG in glioblastoma cells resulted in a rapid and efficient MHC I degradation. In conclusion, CatG is an essential protease for regulating MHC I molecules and thus modulation of CatG activity might present a new avenue for therapeutic intervention. PMID- 26837516 TI - Defect structure and optical phonon confinement in ultrananocrystalline BixSn1 xO2 (x = 0, 0.03, 0.05, and 0.08) synthesized by a sonochemical method. AB - We report the structure of defect and the oxygen vacancy-induced optical phonon confinement in phase pure tetragonal rutile crystal structured ultrananocrystalline BixSn1-xO2 (x = 0, 0.03, 0.05, 0.08) with high surface area synthesized by sonochemical method. As the Bi ion incorporates into the SnO2 host lattice, it replaces the Sn ions marked by the lattice expansion, which leads to the formation of oxygen vacancies so as to maintain charge neutrality. The grain size reduces from 6 nm to 3 nm with increase in Bi content from 0% to 8%. The size effect and the increased oxygen vacancy concentration were found to induce phonon confinement within the grain. This has led to interesting changes in the vibrational spectra of the ultrananocrystalline BixSn1-xO2 as the size reduces below 9 nm. Absence of periodicity beyond this critical particle size relaxes the zone-centre optical phonon selection rule, causing the Raman spectrum to have contributions also from phonons away from the Brillouin-zone centre. The structure of defects, such as the in-plane, bridging and sub-bridging oxygen vacancies present, was confirmed using Raman spectroscopic analysis. The reason for enhancement in photoluminescence behaviour with increased Bi content is discussed. The energy band gap was found to be wider (~4 eV) compared to the bulk and reveals an increasing trend as a function of Bi%. The increase in band gap with decrease in particle size marks the quantum confinement effect. The variation of band gap upon doping is due to the BM shift effect, which arises as a result of the increase in carrier concentration. PMID- 26837515 TI - Prognostic value of (18)F-fluorodeoxyglucose positron emission tomography in patients with gastric neuroendocrine carcinoma and mixed adenoneuroendocrine carcinoma. AB - OBJECTIVE: Gastric neuroendocrine carcinomas (NEC) and mixed adenoneuroendocrine carcinoma (MANEC) are very rare, aggressive tumors of the stomach. We aimed to examine predictive role of pretreatment (18)F-FDG PET/CT-assessed metabolic parameter of primary tumors and metastases in patients with gastric NEC and MANEC. METHODS: We conducted a review of the 27 patients with histopathologically confirmed NECs (n = 10) and MANEC (n = 17) of the stomach at our institution between January 2005 and December 2012. All patients underwent (18)F-FDG-PET examination at diagnosis. Metabolic parameters [SUVmax, SUVmean, metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] of the primary tumor and metastases on baseline PET/CT were analyzed. RESULTS: The median follow-up duration was 39.4 months (95 % CI 20.0-58.1 months) and the median overall survival (OS) was 25.7 months (95 % CI 14.1-37.2 months). All gastric lesions were well visualized (average SUVmax = 12.0, range 3.0-41.8). When subjects were divided into two groups by ROC cut-off value of 210.9 and 612, patients with high TLG in primary lesion and metastases showed poorer prognosis compared to low TLG patients (P = 0.09, P = 0.002, respectively). In the sub-analysis of patients with metastasis (n = 12), patients with high TLG in whole body tumor showed significantly shorter OS compared to those with low TLG (31.7 +/- 11.4 vs. 7.2 +/ 2.1 months, P = 0.006). CONCLUSION: (18)F-FDG PET/CT is useful in evaluating prognosis of advanced gastric cancer with neuroendocrine carcinoma components. Baseline MTV of primary gastric cancer with metastatic disease, and MTV, TLG of metastases may be prognostic markers in patients with gastric NEC and MANEC. PMID- 26837517 TI - Dynamic range multiwavelength particle characterization using analytical ultracentrifugation. AB - We demonstrate how a sophisticated data analysis methodology enables us to perform multiwavelength evaluations of dynamic rotor speed gradient experiments obtained by analytical ultracentrifugation equipped with a multiwavelength detector. Our data evaluation tool HDR-MULTIFIT allows for the accurate analysis of sedimentation coefficient distributions which can be converted to particle size distributions. By means of multiwavelength evaluation, species dependent extinction spectra can be determined even for complex mixtures. Moreover, optical and hydrodynamic properties can be correlated for spherical particles of known optical properties applying multiwavelength evaluation and Mie's theory leading to a significant increase in the dynamic range of the experiment. We provide the theoretical background about the operation principle of our methodology and compare the performance of the multiwavelength analysis to the conventional single wavelength analysis as it is applied in turbidity analysis. We validate our technique using NIST traceable reference particles and show that our technique is universally applicable to materials of known and unknown optical properties, thus clearly extending the possibilities of particle analysis. PMID- 26837518 TI - Luminescence and energy transfer properties of novel Na2.5Y0.5Mg7(PO4)6: R (R = Eu(2+), Tb(3+) and Mn(2+)) phosphors. AB - A series of Eu(2+), Mn(2+) and Tb(3+) singly and co-doped Na2.5Y0.5Mg7(PO4)6 phosphors have been prepared by the solid-state reaction method. X-ray diffraction (XRD) patterns, scanning electron microscopy (SEM), transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS) have been used to characterise the crystal structure, morphology and composition of the as prepared samples. The emission intensities of Mn(2+) and Tb(3+) are enhanced due to an efficient energy transfer from Eu(2+) to Mn(2+) and Tb(3+) in Na2.5Y0.5Mg7(PO4)6. In addition, the energy transfer mechanisms between Mn(2+), Tb(3+) and Eu(2+) have been demonstrated. Similarly, white light emission in the Na2.5Y0.5Mg7(PO4)6 host can be realized by adjusting the co-doped concentration of Eu(2+), Tb(3+) and Mn(2+). The results indicate that the as-prepared phosphors have a great prospect as phosphor-converted materials for light-emitting diodes. PMID- 26837519 TI - Health inequalities by gradients of access to water and sanitation between countries in the Americas, 1990 and 2010. AB - OBJECTIVE: To explore distributional inequality of key health outcomes as determined by access coverage to water and sanitation (WS) between countries in the Region of the Americas. METHODS: An ecological study was designed to explore the magnitude and change-over-time of standard gap and gradient metrics of environmental inequalities in health at the country level in 1990 and 2010 among the 35 countries of the Americas. Access to drinking water and access to improved sanitation facilities were selected as equity stratifiers. Five dependent variables were: total and healthy life expectancies at birth, and infant, under 5, and maternal mortality. RESULTS: Access to WS correlated with survival and mortality, and strong gradients were seen in both 1990 and 2010. Higher WS access corresponded to higher life expectancy and healthy life expectancy and lower infant, under-5, and maternal mortality risks. Burden of life lost was unequally distributed, steadily concentrated among the most environmentally disadvantaged, who carried up to twice the burden than they would if WS were fairly distributed. Population averages in life expectancy and specific mortality improved, but whereas absolute inequalities decreased, relative inequalities remained mostly invariant. CONCLUSIONS: Even with the Region on track to meet MDG 7 on water and sanitation, large environmental gradients and health inequities among countries remain hidden by Regional averages. As the post-2015 development agenda unfolds, policies and actions focused on health equity-mainly on the most socially and environmentally deprived-will be needed in order to secure the right for universal access to water and sanitation. PMID- 26837520 TI - [Public health and intellectual property in Cuba: a conceptual map]. AB - OBJECTIVE: The objective of this study is to analyze the legal framework for health and intellectual property in Cuba and its impact on people's access to health resources and on the roles of different social actors. METHODS: The methods used were those developed by the Pan American Health Organization to implement the project of the Conceptual Map on Public Health and Intellectual Property. RESULTS: Information retrieved specifically on the legal framework for the National Health System, the Intellectual Property System and the strengthening of the country's biopharmaceutical industry-and on the framework's development over time-was processed and analyzed to generate Cuba's Conceptual Map on Public Health and Intellectual Property. CONCLUSIONS: Analysis of Cuba's adaptation of its legal framework and assessment of the interaction between the social actors involved show how the political will that has prevailed over several decades has had a positive impact on people's access to health resources. PMID- 26837521 TI - Effect of a comprehensive ambulatory care model on outcomes of patients with acute coronary syndrome in Colombia. AB - OBJECTIVE: To evaluate the effect of a care program designed according to a comprehensive ambulatory care model (CACM) on the appearance of new cardiovascular/coronary events in patients with acute coronary syndrome. METHODS: Participants in this quasi-experimental intervention study included acute coronary syndrome patients 30-70 years old. The intervention group (n = 165) received care under the CACM, guided by an interdisciplinary team. The CACM included transitional care, risk stratification by severity, physiological profiling (impedance cardiography), and a treatment plan in accordance with current guidelines. The control group (n = 277) received conventional, recommended care in an ambulatory cardiac rehabilitation program. During one year of follow-up, the use of emergency and hospital services related to new cardiovascular and coronary events was evaluated. RESULTS: Differences in the numbers of cardiovascular events (P = 0.003) and coronary events (P = 0.006) experienced by patients were found between the control group and the intervention group. The instantaneous risk of a cardiovascular event (hazard ratio (HR) = 1.80; 95% confidence interval (CI): 1.17-2.75; P = 0.007) and of a coronary event (HR = 1.81; 95% CI: 1.13-2.90; P = 0.013), after adjusting for age, sex, smoking, and compromised coronary arteries, was higher in the control group than the intervention group. CONCLUSIONS: Provision of care under the CACM to patients who had experienced an acute coronary event reduced emergency room visits and rehospitalizations related to new cardiovascular and coronary events by 40%. The average "number needed to treat" (NNT) under the CACM to have an impact on one person (in this case, the prevention of one cardiovascular or coronary event), was 9 and 11 respectively, indicating it is cost-effective. PMID- 26837522 TI - [WHO Framework Convention on Tobacco Control: adherence and establishment in Latin America]. AB - OBJECTIVE: To draw an overview of the adherence of countries around the world to the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) and to describe the establishment of WHO FCTC recommended measures in Latin American countries. METHODS: This descriptive study was based on analysis of documents and secondary data to determine the status of countries from the six WHO regions regarding adherence to the FCTC. After that, the establishment of recommended measures until the year 2012 was mapped in all States Parties and particularly in 12 Latin American States Parties. Finally, the degree to which FCTC measures had been established in Brazil, Chile, Colombia, Mexico, and Venezuela was assessed (incipient, intermediate, or advanced). This step took into consideration the measures covered by four domains - reduction in the demand for tobacco, reduction in the offer of tobacco, reduction in damage to the environment and to the health of people caused by tobacco, and support for quitting the use of tobacco. RESULTS: Until August 2015, 180 countries had joined as States Parties to the FCTC. Considering the 126 countries that submitted global progress reports in the 2012 cycle, the most prevalent measures adopted referred to the protection against exposure to tobacco smoke (83.0% for all countries and 100% for the group of Latin American countries). Among the five countries selected for detailed analysis, the measures referring to the reduction of demand and offer of tobacco were the most frequent. Measures focused on reducing environmental damage were rare. Brazil and Mexico had the most advanced FCTC status among the studied countries. CONCLUSIONS: Latin America presented a high proportion of States Parties with established FCTC recommended measures. The heterogeneity of the FCTC status in the five selected countries suggests that the implementation of tobacco control policies depends on specific aspects of each country. PMID- 26837523 TI - [Infant mortality from congenital malformations in Chile: temporal and spatial analysis, 1997-2011]. AB - OBJECTIVE: To analyze the spatial and temporal distribution (1997-2011) of infant mortality resulting from congenital malformations (CM) in Chile. METHODS: Data on births and deaths among infants aged less than one year using ICD-10 coding were obtained from the National Statistics Institute. The percentage of deaths from CM (PD-CM) and the infant mortality rate from CM (IMR-CM) during three different periods (1997-2001, 2002-2009, 2007-2011) were estimated for Chile's administrative and natural regions (Norte Grande, Norte Chico, Central, Austral, and Sur), broken down by systems (nervous, cardiovascular, digestive, genitourinary, musculoskeletal, and chromosomal abnormalities) and by 28 specific malformations. The secular trend and the variation in the risk of death were estimated using a Poisson regression model. RESULTS: For the whole of Chile, the secular trend for the IMR-CM was negative, and the secular trend for the PD-CM was positive (P < 0,01). The IMR-CM and the PD-CM both showed mild spatial heterogeneity in all administrative and natural regions. The Central region was the natural region that came closest to showing the pattern observed nationwide. The IMR-CM involving the nervous and cardiovascular systems and specific types of CM (anencephaly, spina bifida, and atrial and ventricular septal defects) showed a negative secular trend. For Chile as a whole, the pattern of infant mortality from CM is marked by a drop in the IMR-CM and by an increase in the PD-CM over the period from 1997 to 2011. CONCLUSION: The findings suggest that Chile is in the latter stages of the epidemiological transition with respect to the causes of infant mortality. However, these indicators show disparities between regions, more pronounced in the south of the country. PMID- 26837524 TI - Post-introduction economic evaluation of pneumococcal conjugate vaccination in Ecuador, Honduras, and Paraguay. AB - OBJECTIVE: A decision-analytic model was constructed to evaluate the economic impact of post-introduction pneumococcal conjugate vaccine (PCV) programs in Ecuador, Honduras, and Paraguay from the societal perspective. METHODS: Hypothetical birth cohorts were followed for a 20-year period in each country. Estimates of disease burden, vaccine effectiveness, and health care costs were derived from primary and secondary data sources. Costs were expressed in 2014 US$. Sensitivity analyses were performed to assess the impact of model input uncertainties. RESULTS: Over the 20 years of vaccine program implementation, the health care costs per case ranged from US$ 764 854 to more than US$ 1 million. Vaccination prevented more than 50% of pneumococcal cases and deaths per country. At a cost of US$ 16 per dose, the cost per disability-adjusted life year (DALY) averted for the 10-valent PCV (PCV10) and the 13-valet PCV (PCV13) ranged from US$ 796 (Honduras) to US$ 1 340 (Ecuador) and from US$ 691 (Honduras) to US$ 1 166 (Ecuador) respectively. At a reduced price (US$ 7 per dose), the cost per DALY averted ranged from US$ 327 (Honduras) to US$ 528 (Ecuador) and from US$ 281 (Honduras) to US$ 456 (Ecuador) for PCV10 and PCV13 respectively. Several model parameters influenced the results of the analysis, including vaccine price, vaccine efficacy, disease incidence, and costs. CONCLUSIONS: The economic impact of post-introduction PCV needs to be assessed in a context of uncertainty regarding changing antibiotic resistance, herd and serotype replacement effects, differential vaccine prices, and government budget constraints. PMID- 26837525 TI - [Epidemiological trends in bovine paralytic rabies in central Mexico, 2001-2013]. AB - OBJECTIVE: To determine the geospatial distribution of bovine paralytic rabies cases transmitted by Desmodus rotundus in the Mexican states of Guanajuato, Queretaro, and San Luis Potosi. METHODS: This was a cross-sectional epidemiological study based on cases reported during statewide campaigns for the control of bovine paralytic rabies in Guanajuato (2008-2013), Queretaro (2005 2013) and San Luis Potosi (2001-2013). All cases were confirmed by direct immunofluorescence. Maps showing the distribution of cases by year and species were constructed using ArcMap version 10.1. To identify areas where conditions favor the appearance of cases, bioclimatic variables were combined with georeferenced cases using MaxEnt version 3.3.3. RESULTS: Of the 1037 cases recorded, 911 (87.9%) occurred in San Luis Potosi, 82 (7.9%) in Queretaro, and 44 (4.2%) in Guanajuato. Of the total number of cases, 87.4% occurred at altitudes of less than 1500 meters above sea level. In Guanajuato and Queretaro, 77.3% and 42.3% of the cases, respectively, occurred at altitudes greater than 1 500 meters above sea level. Peak incidence was recorded from December to March. The V11 antigenic variant of the virus was the most common (173 cases); it was found in all three states. In the endemic channel, the average number of cases remains within the security zone from January to March but exceeds the median value from April to June. The spatial distribution of cases shows that the disease has spread recently, which correlates with the presence of the vampire bat. CONCLUSIONS: Bovine paralytic rabies has spread to areas that were formerly free of the disease. Environmental characteristics and the altitude above sea level do not limit the appearance of cases. Constant monitoring should be conducted for early case detection. Vaccination should take place before the rainy season starts, without waiting for outbreaks to occur. PMID- 26837526 TI - Barriers and facilitators to establishing a national public health observatory. AB - OBJECTIVE: To determine what stakeholders perceive as barriers and facilitators to creating a national public health observatory (PHO) in Trinidad and Tobago. METHODS: A descriptive study was conducted based on 15 key informant interviews carried out from April to September 2013. The key informants worked within the health care sector in Trinidad and Tobago. Using a semi-structured interview guide, information was collected on knowledge, attitudes, and beliefs about creating a PHO; barriers and facilitators to creating and sustaining a PHO; legal considerations; and human resource and information technology requirements. Common themes of the responses were identified. RESULTS: The majority of participants supported the development of a national PHO, recognized its value in informing their work, and indicated that a national PHO could 1) provide information to support evidence-informed decision-making for health policy and strategic planning; 2) facilitate data management by establishing data policies, procedures, and standards; 3) increase the use of data by synthesizing and disseminating information; and 4) provide data for benchmarking. However, a number of barriers were identified, including 1) the perception that data collection is not valued; 2) untimely availability of data; 3) limited data synthesis, dissemination, and utilization to inform decision-making; and 4) challenges related to the allocation of human resources and existing information technology. CONCLUSIONS: Key informants support the development of a national PHO in Trinidad and Tobago. The findings align well within the components of the conceptual framework for establishing national health observatories. A stepwise approach to establishing a national PHO in Trinidad and Tobago, beginning with structural components and followed by functional components, is recommended. A national PHO in Trinidad and Tobago could serve as a model for other countries in the Caribbean. PMID- 26837527 TI - [Global funding for papers of excellence on smoking, 2010-2014]. AB - OBJECTIVE: The objective of this study was to investigate the funding received by papers of excellence on smoking at the global level between 2010 and 2014 through the Web of Science, and to find out if funding is associated with greater impact. METHOD: We searched the Science Citation Index Expanded (SCIE) and the Social Sciences Citation Index (SSCI) through the Web of Science platform on 20 May 2015 (typology consisting of originals and reviews for the period from 2010 to 2014). The search strategy was "smok*" OR "tobac*." To select the papers of excellence, we picked those that had an h index (i.e., number of articles having at least that many citations) from among the papers in the overall sample generated by the strategy. RESULTS: Of the 193 papers of excellence on smoking that were identified, 158 had received funding from 279 different financing institutions that intervened 522 times. The funding came primarily from government agencies, private foundations, and the pharmaceutical industry. Public funding declined and private funding increased over the years included in the analysis. Receipt of funding was not associated with greater impact at a later date. CONCLUSIONS: Most of the papers of excellence on smoking received external funding primarily from government agencies, private foundations, and the pharmaceutical industry. Public funding has decreased, while private funding has increased. Receipt of funding was not associated with greater impact at a later date. PMID- 26837528 TI - [Alcohol use as a necessary cause of death in Brazil, 2010-2012]. AB - OBJECTIVE: To describe mortality from diseases, conditions, and injuries for which alcohol consumption is a necessary cause during the 2010-2012 triennium in Brazil. METHODS: A descriptive study was conducted with data from the Brazilian Ministry of Health's Mortality Information System (SIM). The analysis included deaths whose primary cause was classified as any of the 78 codes of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) corresponding to the diseases, conditions, and injuries for which the use of alcohol is a necessary cause. RESULTS: Deaths with alcohol consumption as a necessary cause totaled 55 380 (88.5% in men). The crude mortality rate for the triennium was 9.6/100 000 people in the overall population, 17.35/100 000 men in males, and 2.15/100 000 women in females. Higher mortality rates were observed in the 50-59 year (28.45) and 60-69 year (27.23) age groups and among people with black or brown skin color (10.15). The Northeast (11.70) and Midwest (11.04) regions exhibited higher age-adjusted mortality rates. Liver diseases were the leading cause of death (55.3%). CONCLUSIONS: Mortality from causes related to alcohol consumption is high in Brazil, especially among men, people aged 50-69 years, and residents in the Northeast and Midwest regions. PMID- 26837529 TI - Building capacity for human genetics and genomics research in Trinidad and Tobago. AB - Advances in human genetics and genomic sciences and the corresponding explosion of biomedical technologies have deepened current understanding of human health and revolutionized medicine. In developed nations, this has led to marked improvements in disease risk stratification and diagnosis. These advances have also led to targeted intervention strategies aimed at promoting disease prevention, prolonging disease onset, and mitigating symptoms, as in the well known case of breast cancer and the BRCA1 gene. In contrast, in the developing nation of Trinidad and Tobago, this scientific revolution has not translated into the development and application of effective genomics-based interventions for improving public health. While the reasons for this are multifactorial, the underlying basis may be rooted in the lack of pertinence of internationally driven genomics research to the local public health needs in the country, as well as a lack of relevance of internationally conducted genetics research to the genetic and environmental contexts of the population. Indeed, if Trinidad and Tobago is able to harness substantial public health benefit from genetics/genomics research, then there is a dire need, in the near future, to build local capacity for the conduct and translation of such research. Specifically, it is essential to establish a national human genetics/genomics research agenda in order to build sustainable human capacity through education and knowledge transfer and to generate public policies that will provide the basis for the creation of a mutually beneficial framework (including partnerships with more developed nations) that is informed by public health needs and contextual realities of the nation. PMID- 26837530 TI - Names for cigars or cigarettes used by the Latino consumer in the United States of America. PMID- 26837531 TI - Talaroketals A and B, unusual bis(oxaphenalenone) spiro and fused ketals from the soil fungus Talaromyces stipitatus ATCC 10500. AB - Two novel oxaphenalenone dimers, talaroketals A () and B (), were isolated from the soil fungus Talaromyces stipitatus. Their structures and absolute configurations were determined on the basis of spectroscopic analyses, X-ray diffraction experiments and electronic circular dichroism. Compound () features a rare benzannulated 5,6-spiroketal ring system within the dimeric bis(oxaphenalenone) skeleton while the parent compound () harbors a fused bicyclic furano-pyran moiety. These two compounds may biogenetically result from the reaction of duclauxin with a dihydrofuran derivative of botryodiplodin. Additionally, talaroketals A () and B () display modest antimicrobial activity against Staphylococcus aureus. PMID- 26837532 TI - Convection-Enhanced Biopatterning with Recirculation of Hydrodynamically Confined Nanoliter Volumes of Reagents. AB - We present a new methodology for efficient and high-quality patterning of biological reagents for surface-based biological assays. The method relies on hydrodynamically confined nanoliter volumes of reagents to interact with the substrate at the micrometer-length scale. We study the interplay between diffusion, advection, and surface chemistry and present the design of a noncontact scanning microfluidic device to efficiently present reagents on surfaces. By leveraging convective flows, recirculation, and mixing of a processing liquid, this device overcomes limitations of existing biopatterning approaches, such as passive diffusion of analytes, uncontrolled wetting, and drying artifacts. We demonstrate the deposition of analytes, showing a 2- to 5 fold increase in deposition rate together with a 10-fold reduction in analyte consumption while ensuring less than 6% variation in pattern homogeneity on a standard biological substrate. In addition, we demonstrate the recirculation of a processing liquid using a microfluidic probe (MFP) in the context of a surface assay for (i) probing 12 independent areas with a single microliter of processing liquid and (ii) processing a 2 mm(2) surface to create 170 antibody spots of 50 * 100 MUm(2) area using 1.6 MUL of liquid. We observe high pattern quality, conservative usage of reagents, micrometer precision of localization and convection-enhanced fast deposition. Such a device and method may facilitate quantitative biological assays and spur the development of the next generation of protein microarrays. PMID- 26837533 TI - Downregulation of dickkopf-1 enhances the proliferation and osteogenic potential of fibroblasts isolated from ankylosing spondylitis patients via the Wnt/beta catenin signaling pathway in vitro. AB - BACKGROUND: Heterotopic ossification of the entheses is one of the most distinctive features in ankylosing spondylitis (AS). Fibroblasts are potential target cells for heterotopic ossification. The Wnt/beta-catenin pathway and its inhibitor dickkopf-1 (DKK-1) regulate bone formation. DKK-1 expression in human AS tissues has not been documented. OBJECTIVE: The purpose of the current study was to investigate the expression of DKK-1 in AS tissues and to elucidate its role in fibroblasts proliferation and osteogenesis in AS. METHODS: DKK-1 expression was assessed by western blotting, real time-polymerase chain reaction (RT-PCR), and immunohistochemistry analysis of hip synovial tissues obtained from AS and control patients. Fibroblasts were isolated, cultured, and transfected with lentiviral vectors for overexpressing human DKK-1 or an shRNA for silencing DKK-1. MTS [(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) 2-(4 sulfophenyl)-2H-tetrazolium] and a 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay were used to detect AS fibroblasts proliferation after transfection. The expression levels of beta-catenin, phosphorylated beta-catenin, c-Myc, cyclin D1, and the osteogenesis markers alkaline phosphatase (ALP), osteocalcin (OCN), and Runt-related transcription factor 2 (Runx2) were then examined by western blot analysis. Alizarin red staining (ARS) was also used to observe biomineralization activity. RESULTS: DKK-1 was downregulated in hip synovial tissues from AS patients compared to that observed in controls. AS fibroblasts exhibited excessive proliferation, a higher growth rate, and a decreased apoptotic rate. EdU assay demonstrated that DKK-1 suppressed the growth of AS fibroblasts. Downregulation of DKK-1 decreased the phosphorylation of beta-catenin and upregulated the expression of beta-catenin, c-Myc, cyclin D1, and osteogenesis markers. Overexpression of DKK-1 had the opposite effect, resulting in the inhibition of the Wnt/beta-catenin pathway. ARS showed an increase in biomineralization activity after the inhibition of DKK-1. CONCLUSIONS: AS fibroblasts are characterized by an imbalance between proliferation and apoptosis. DKK-1 may play a role in switching to new bone formation in AS progression. PMID- 26837534 TI - Marine natural products. AB - This review covers the literature published in 2014 for marine natural products (MNPs), with 1116 citations (753 for the period January to December 2014) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1378 in 456 papers for 2014), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included. PMID- 26837535 TI - Pea weevil damage and chemical characteristics of pea cultivars determining their resistance to Bruchus pisorum L. AB - Bruchus pisorum (L.) is one of the most intractable pest problems of cultivated pea in Europe. Development of resistant cultivars is very important to environmental protection and would solve this problem to a great extent. Therefore, the resistance of five spring pea cultivars was studied to B. pisorum: Glyans, Modus; Kamerton and Svit and Pleven 4 based on the weevil damage and chemical composition of seeds. The seeds were classified as three types: healthy seeds (type one), damaged seeds with parasitoid emergence holes (type two) and damaged seeds with bruchid emergence holes (type three). From visibly damaged pea seeds by pea weevil B. pisorum was isolated the parasitoid Triaspis thoracica Curtis (Hymenoptera, Braconidae). Modus, followed by Glyans was outlined as resistant cultivars against the pea weevil. They had the lowest total damaged seed degree, loss in weight of damaged seeds (type two and type three) and values of susceptibility coefficients. A strong negative relationship (r = -0.838) between the weight of type one seeds and the proportion of type three seeds was found. Cultivars with lower protein and phosphorus (P) content had a lower level of damage. The crude protein, crude fiber and P content in damaged seeds significantly or no significantly were increased as compared with the healthy seeds due to weevil damage. The P content had the highest significant influence on pea weevil infestation. Use of chemical markers for resistance to the creation of new pea cultivars can be effective method for defense and control against B. pisorum. PMID- 26837536 TI - Increasing patient knowledge on the proper usage of a PCA machine with the use of a post-operative instructional card. AB - OBJECTIVES: The purpose of this study was to see if an instructional card, attached to the PCA machine following total hip arthroplasty describing proper use of the device, would positively affect subjects' understanding of device usage, pain scores, pain medication consumption and satisfaction. METHODS: Eighty adults undergoing total hip replacements who had been prescribed PCA were randomized into two study groups. Forty participants received the standard post operative instruction on PCA device usage at our institution. The other 40 participants received the standard of care in addition to being given a typed instructional card immediately post-operatively, describing proper PCA device use. This card was attached to the PCA device during their recovery period. On post-operative day one, each patient completed a questionnaire on PCA usage, pain scores and satisfaction scores. RESULTS: The pain scores in the Instructional Card group were significantly lower than the Control group (p = 0.024). Subjects' understanding of PCA usage was also improved in the Instructional Card group for six of the seven questions asked. CONCLUSION: The findings from this study strongly support that postoperative patient information on proper PCA use by means of an instructional card improves pain control and hence the overall recovery for patients undergoing surgery. In addition, through improved understanding it adds an important safety feature in that patients and potentially their family members and/or friends may refrain from PCA-by-proxy. This article demonstrates that the simple intervention of adding an instructional card to a PCA machine is an effective method to improve patients' knowledge as well as pain control and potentially increase the safety of the device use. PMID- 26837537 TI - Lancet retracts paper by disgraced Canadian researcher. PMID- 26837538 TI - The physics of confined flow and its application to water leaks, water permeation and water nanoflows: a review. AB - This review assesses the current state of understanding of the calculation of the rate of flow of gases, vapours and liquids confined in channels, in porous media and in permeable materials with an emphasis on the flow of water and its vapour. One motivation is to investigate the relation between the permeation rate of moisture and that of a noncondensable test gas such as helium, another is to assist in unifying theory and experiment across disparate fields. Available theories of single component ideal gas flows in channels of defined geometry (cylindrical, rectangular and elliptical) are described and their predictions compared with measurement over a wide range of conditions defined by the Knudsen number. Theory for two phase flows is assembled in order to understand the behaviour of four standard water leak configurations: vapour, slug, Washburn and liquid flow, distinguished by the number and location of phase boundaries (menisci). Air may or may not be present as a background gas. Slip length is an important parameter that greatly affects leak rates. Measurements of water vapour flows confirm that water vapour shows ideal gas behaviour. Results on carbon nanotubes show that smooth walls may lead to anomalously high slip lengths arising from the properties of 'confined' water. In porous media, behaviour can be matched to the four standard leaks. Traditional membrane permeation models consider that the permeant dissolves, diffuses and evaporates at the outlet side, ideas we align with those from channel flow. Recent results on graphite oxide membranes show examples where helium which does not permeate while at the same time moisture is almost unimpeded, again a result of confined water. We conclude that while there is no a priori relation between a noncondensable gas flow and a moisture flow, measurements using helium will give results within two orders of magnitude of the moisture flow rate, except in the case where there is anomalous slip or confined water, when moisture specific measurements are essential. PMID- 26837539 TI - A survey-based study of factors that motivate nurses to protect the privacy of electronic medical records. AB - BACKGROUND: The purpose of this study is to investigate factors that motivate nurses to protect privacy in electronic medical records, based on the Decomposed Theory of Planned Behavior. METHODS: This cross-sectional study used questionnaires to collect data from nurses in a large tertiary care military hospital in Taiwan. RESULTS: The three hundred two (302) valid questionnaires returned resulted in a response rate of 63.7 %. Structural equation modeling identified that the factors of attitude, subjective norm, and perceived behavioral control of the nurses significantly predicted the nurses' intention to protect the privacy of electronic medical records. Further, perceived usefulness and compatibility, peer and superior influence, self-efficacy and facilitating conditions, respectively predicted these three factors. CONCLUSIONS: The results of our study may provide valuable information for education and practice in predicting nurses' intention to protect privacy of electronic medical records. PMID- 26837540 TI - Illness perception and quality of life of HIV-positive persons: mediation effects of tenacious and flexible goal pursuit. AB - Medical advances contribute to raise life expectancy of people living with HIV/AIDS (PLHIV). However, they still face challenges related to the disease, thus, quality of life (QOL) became a priority on the field. The self-regulatory model (SRM) guided this study. Illness perceptions (IP) are the beliefs, cognitions, representations of a disease, impacting PLHIV coping strategies and QOL. Tenacious goal pursuit (TGP) is the pursuit of goals with determination, flexible goal adjustment (FGA) is doing it with flexibility, disengaging if necessary, they can both be considered as coping strategies. This study aims to measure the impact of HIV Perception in the QOL of PLHIV mediated by the TGP and FGA. Data was collected from 196 PLHIV with the WHOQOL-HIV Bref, the Brief-IPQ and the FGA and TGP scales. Structural equation model provided a good fit consistent with the theoretical SRM. IP, TGP and FGA had direct effects on the QOL of PLHIV. IP had also an indirect effect (partially mediated by TGP/FGA), suggesting that TGP/FGA reduce the impact of a threatening IP in the QOL. Goal oriented interventions should focus in the HIV perception of PLHIV to ameliorate their QOL. PMID- 26837541 TI - Gene expression profiling of rubella virus infected primary endothelial cells of fetal and adult origin. AB - BACKGROUND: Rubella virus (RV) infection is usually a mild illness in children and adults. However, maternal infection during the first trimester of pregnancy can lead to congenital rubella syndrome (CRS) in the infant. Fetuses with CRS show damage to the endothelium of the heart and blood vessels; thus, it has been speculated that the clinical manifestations associated with CRS may be a result of endothelial cells persistently infected with RV. Here, we compared the effects of RV infection on gene expression in primary endothelial cells of fetal (HUVEC) and of adult (HSaVEC) origin by transcriptional profiling. RESULTS: More than 75 % of the genes differentially regulated following RV infection were identical in both cell types. Gene Ontology (GO) analysis of these commonly regulated genes showed an enrichment of terms involved in cytokine production and cytokine regulation. Increased accumulation of inflammatory cytokines following RV infection was verified by protein microarray. Interestingly, the chemokine CCL14, which is implicated in supporting embryo implantation at the fetal-maternal interface, was down-regulated following RV infection only in HUVEC. Most noticeably, when analyzing the uniquely regulated transcripts for each cell type, GO term-based cluster analysis of the down-regulated genes of HUVEC revealed an enrichment of the GO terms "sensory organ development", "ear development" and "eye development". CONCLUSION: Since impairment in vision and hearing are the most prominent clinical manifestations observed in CRS patients, the here detected down-regulated genes involved in the development of sensory organs sheds light on the molecular mechanisms that may contribute to the teratogenic effect of RV. PMID- 26837542 TI - Dietary supplementation of pyrroloquinoline quinone disodium protects against oxidative stress and liver damage in laying hens fed an oxidized sunflower oil added diet. AB - The protective effects of dietary pyrroloquinoline quinone disodium (PQQ.Na2) supplementation against oxidized sunflower oil-induced oxidative stress and liver injury in laying hens were examined. Three hundred and sixty 53-week-old Hy-Line Gray laying hens were randomly allocated into one of the five dietary treatments. The treatments included: (1) a diet containing 2% fresh sunflower oil; (2) a diet containing 2% thermally oxidized sunflower oil; (3) an oxidized sunflower oil diet with 100 mg/kg of added vitamin E; (4) an oxidized sunflower oil diet with 0.08 mg/kg of PQQ.Na2; and (5) an oxidized sunflower oil diet with 0.12 mg/kg of PQQ.Na2. Birds fed the oxidized sunflower oil diet showed a lower feed intake compared to birds fed the fresh oil diet or oxidized oil diet supplemented with vitamin E (P=0.009). Exposure to oxidized sunflower oil increased plasma malondialdehyde (P<0.001), hepatic reactive oxygen species (P<0.05) and carbonyl group levels (P<0.001), but decreased plasma glutathione levels (P=0.006) in laying hens. These unfavorable changes induced by the oxidized sunflower oil diet were modulated by dietary vitamin E or PQQ.Na2 supplementation to levels comparable to the fresh oil group. Dietary supplementation with PQQ.Na2 or vitamin E increased the activities of total superoxide dismutase and glutathione peroxidase in plasma and the liver, when compared with the oxidized sunflower oil group (P<0.05). PQQ.Na2 or vitamin E diminished the oxidized sunflower oil diet induced elevation of liver weight (P=0.026), liver to BW ratio (P=0.001) and plasma activities of alanine aminotransferase (P=0.001) and aspartate aminotransferase (P<0.001) and maintained these indices at the similar levels to the fresh oil diet. Furthermore, oxidized sunflower oil increased hepatic DNA tail length (P<0.05) and tail moment (P<0.05) compared with the fresh oil group. Dietary supplementation of PQQ.Na2 or vitamin E decreased the oxidized oil diet induced DNA tail length and tail moment to the basal levels in fresh oil diet. These results indicate that PQQ.Na2 is a potential antioxidant and is as effective against oxidized oil-related liver injury in laying hens as vitamin E. The protective effects of PQQ.Na2 against liver damage induced by oxidized oil may be partially due to its role in the scavenging of free radicals, inhibiting of lipid peroxidation and enhancing of antioxidant defense systems. PMID- 26837543 TI - Extracorporeal support for pulmonary resection: current indications and results. AB - Extracorporeal assistances are exponentially used for patients, with acute severe but reversible heart or lung failure, to provide more prolonged support to bridge patients to heart and/or lung transplantation. However, experience of use of extracorporeal assistance for pulmonary resection is limited outside lung transplantation. Airways management with standard mechanical ventilation system may be challenging particularly in case of anatomical reasons (single lung), presence of respiratory failure (ARDS), or complex tracheo-bronchial resection and reconstruction. Based on the growing experience during lung transplantation, more and more surgeons are now using such devices to achieve good oxygenation and hemodynamic support during such challenging cases. We review the different extracorporeal device and attempt to clarify the current practice and indications of extracorporeal support during pulmonary resection. PMID- 26837547 TI - A Humanitarian and a Great Indian. PMID- 26837548 TI - Stereotactic ablative body radiotherapy for primary kidney cancer: what have we learned from prospective trials and what does the future hold? PMID- 26837549 TI - Poorly Differentiated Thyroid Carcinoma. AB - Poorly differentiated thyroid carcinoma (PDTC) has been recognized for the past 30 years as an entity showing intermediate differentiation and clinical behavior between well-differentiated thyroid carcinomas (ie, papillary thyroid carcinoma and follicular thyroid carcinoma) and anaplastic thyroid carcinoma; however, there has been considerable controversy around the definition of PDTC. In this review, the evolution in the definition of PDTC, current diagnostic criteria, differential diagnoses, potentially helpful immunohistochemical studies, and molecular alterations are discussed with the aim of highlighting where the diagnosis of PDTC currently stands. PMID- 26837550 TI - Immunohistochemical Diagnosis of Thyroid Tumors. AB - Recent insight into the molecular mechanisms of thyroid carcinogenesis has led to studies involving newly directed antibodies. With the introduction of new molecular targeted therapies, these antibodies may represent useful predictors of therapeutic response in tumors unresponsive to radioiodine or insensitive to conventional antitumor therapies. These markers complement the development of markers that are able to discern benign from malignant entities, including hyalinizing trabecular tumors, oncocytic neoplasms, and follicular variant of papillary thyroid carcinoma. The use of antibodies directed to proteins generated by mutated genes may represent a cost-effective method for diagnosing and managing patients affected by thyroid tumors. PMID- 26837551 TI - Tumor-Associated Inflammatory Cells in Thyroid Carcinomas. AB - The complex interactions between immune cells and tumor cells in cancer play a major role in tumor development and subsequent patient outcomes. Different types of tumor-associated inflammatory cells (TAICs), such as dendritic cells, macrophages, lymphocytes, and mast cells, have been recognized for many years in several tumors; however, the role of TAICs in cancer is still not completely understood. This review article focuses on the major types of TAICs, including their general role in cancer and, more specifically, their role and distribution in thyrocyte-derived carcinomas. PMID- 26837552 TI - Parathyroid: The Pathology of Hyperparathyroidism. AB - This review focuses on the pathologic entities associated with hyperparathyroidism in humans. A discussion of the lesions, their embryology, and pathologic features is included. Immunohistology, cytopathology, and a brief overview of molecular aspects of the lesion are included. PMID- 26837553 TI - Assessing Biological Aggression in Adrenocortical Neoplasia. AB - Pathologists are highly skilled at the evaluation of adrenal neoplasms. Occasional adrenocortical tumors can be diagnostically challenging and supplementary tools can assist in these cases. Histologic and molecular studies support a model that includes 2 broad classes of adrenocortical carcinoma with distinct somatic genetic alterations and clinical outcomes. Pathologists should endeavor to grade adrenocortical carcinomas to assign each case into one of these 2 classes. Mitotic grading by mitotic counting and Ki-67 immunohistochemistry represent the most practicable and informative methods currently available. PMID- 26837554 TI - Paragangliomas Arising in the Head and Neck: A Morphologic Review and Genetic Update. AB - Seventy percent of parasympathetic paragangliomas arise in the head and neck and are nonsecretory. Awareness of the differential diagnosis based on location, overlapping morphology, and immunohistochemical profiles aids in the correct diagnosis, particularly on limited tissue samples. Moreover, 30% to 40% of head and neck paragangliomas are known to be associated with hereditary syndromes, with the succinate dehydrogenase enzyme family comprising the most frequent association. The pathologist's role is becoming increasing critical for facilitating optimal patient care beyond the initial tissue diagnosis of paraganglioma to include screening and documenting potential hereditary tumors requiring further patient counseling and testing. PMID- 26837555 TI - Pancreatic Neuroendocrine Neoplasms. AB - Pancreatic neuroendocrine neoplasms (Pan-NENs) are rare but clinically important lesions. Pan-NENs are known for and often categorized by their capacity to produce clinical syndromes mediated by the production of hormones. Despite sometimes presenting dramatically from excessive hormone production, not all Pan NENs produce functional hormone, and they can pose diagnostic challenges to practicing pathologists. Distinguishing Pan-NENs from mimics can be crucial, because Pan-NENs carry different prognoses and have unique treatments available due to their specific biological properties. This article reviews the current categorization and features of Pan-NENs. PMID- 26837556 TI - Familial Endocrine Syndromes. AB - Endocrine tumors may present as sporadic events or as part of familial endocrine syndromes. Familial endocrine syndromes (or inherited tumor/neoplasm syndromes) are characterized by multiple tumors in multiple organs. Some morphologic findings in endocrine tumor histopathology may prompt the possibility of familial endocrine syndromes, and these recognized histologic features may lead to further molecular genetic evaluation of the patient and family members. Subsequent evaluation for these syndromes in asymptomatic patients and family members may then be performed by genetic screening. PMID- 26837559 TI - Endocrine Pathology: Treading Water in a Shark Tank of Uncertain Malignant Potential. PMID- 26837562 TI - In Response to "Serum Tumor Marker Use in Patients With Advanced Solid Tumors". PMID- 26837563 TI - Reply to F. Dayyani et al. PMID- 26837564 TI - The Promise and Burden of Peer Review in Radiation Oncology. PMID- 26837565 TI - Association Between the Number of Suppliers for Critical Antineoplastics and Drug Shortages: Implications for Future Drug Shortages and Treatment. AB - PURPOSE: Congress has identified the critical need to evaluate contributors to ongoing cancer drug shortages. Because increased competition may reduce drug shortages, we investigated the association between the number of suppliers for first-line breast, colon, and lung antineoplastics and drug shortages. DATA AND METHODS: Using the 2003 to 2014 Red Book and national drug shortage data from the University of Utah's Drug Information Service, we used exploratory analysis to quantify time trends in first-line drug suppliers and shortages by cancer site. Generalized mixed models were used to examine the association between the number of suppliers for individual drugs and resulting drug shortages. RESULTS: Among 35 antineoplastic drugs approved for first-line treatment of breast, colon, and lung cancer, the number of unique suppliers varied greatly (range, 1 to 19). In 2003, 12.5%,33.3%, and 0%of breast, colon, and lung cancer drugs, respectively, experienced shortages, which increased overall by 2014, to 40.0%, 37.5%, and 54.5%, respectively. Having as mall number of drug suppliers more than doubled the odds of shortages compared with a large number of suppliers (>=5), although the results were only statistically significant with three to four suppliers (odds ratio = 2.6, P = .049) but not with one to two suppliers (odds ratio = 3.49, P = .105). One of the strongest risk factors for drug shortages was the age of the drug, with older drugs significantly more likely to experience shortages (P<.001). CONCLUSION: Cancer drugs with a small number of suppliers had a higher risk of drug shortages than did those with$5 suppliers, but the relationship was nonlinear. Because the age of the drug is the strongest risk factor, future studies should explore underlying causes of shortages in older drugs. PMID- 26837566 TI - Sulphuric acid marketed in water bottle in India: A cause for fatal accidental poisoning in an adult. AB - Corrosive acid ingestion is a rare but serious health hazard with fatal complications. Cases of suicidal and accidental acid ingestion have been documented in the scientific literature. Accidental acid poisoning due to a mistaken identity of the bottle containing sulphuric acid is a matter of grave concern especially in a household set-up. We hereby report a fatal case of accidental sulphuric acid ingestion in an adult, who unsuspectingly swallowed about 50 ml of 'toilet-cleaner' at his residence. The bottle containing the acid was recently purchased from a local vendor and placed with water bottles in the kitchen. The autopsy and toxicological findings of this case are discussed in this paper with discussion of medico-legal issues on the sale and use of such corrosive acids in illegal bottles and its subsequent health hazards in India. PMID- 26837567 TI - Sudden unexpected death due to strangulated inguinal hernia. AB - Sudden unwitnessed, unexpected deaths when the bodies are found in public places require a complete and meticulous medicolegal autopsy to ascertain the cause and manner of death to avoid further unnecessary investigations by the legal authorities. Such deaths attributed to gastrointestinal causes at autopsy are relatively uncommon. We report a case of sudden unexpected death due to strangulated inguinal hernia in a 60-year-old man. The body was discovered in a public area near a place of worship. The present case illustrates a potentially preventable sudden unexpected death due to a surgically correctable gastrointestinal condition. In the present case, the individual feared being hospitalised for treatment of his scrotal swelling with potential surgery and the eventual loss of daily income. In our opinion, such apprehensions may have delayed the potentially life-saving hospital surgical intervention in the individual. PMID- 26837568 TI - A Combined Experimental and Theoretical Study on the Formation of the 2-Methyl-1 silacycloprop-2-enylidene Molecule via the Crossed Beam Reactions of the Silylidyne Radical (SiH; X(2)Pi) with Methylacetylene (CH3CCH; X(1)A1) and D4 Methylacetylene (CD3CCD; X(1)A1). AB - The bimolecular gas-phase reactions of the ground-state silylidyne radical (SiH; X(2)Pi) with methylacetylene (CH3CCH; X(1)A1) and D4-methylacetylene (CD3CCD; X(1)A1) were explored at collision energies of 30 kJ mol(-1) under single collision conditions exploiting the crossed molecular beam technique and complemented by electronic structure calculations. These studies reveal that the reactions follow indirect scattering dynamics, have no entrance barriers, and are initiated by the addition of the silylidyne radical to the carbon-carbon triple bond of the methylacetylene molecule either to one carbon atom (C1; [i1]/[i2]) or to both carbon atoms concurrently (C1-C2; [i3]). The collision complexes [i1]/[i2] eventually isomerize via ring-closure to the c-SiC3H5 doublet radical intermediate [i3], which is identified as the decomposing reaction intermediate. The hydrogen atom is emitted almost perpendicularly to the rotational plane of the fragmenting complex resulting in a sideways scattering dynamics with the reaction being overall exoergic by -12 +/- 11 kJ mol(-1) (experimental) and -1 +/ 3 kJ mol(-1) (computational) to form the cyclic 2-methyl-1-silacycloprop-2 enylidene molecule (c-SiC3H4; p1). In line with computational data, experiments of silylidyne with D4-methylacetylene (CD3CCD; X(1)A1) depict that the hydrogen is emitted solely from the silylidyne moiety but not from methylacetylene. The dynamics are compared to those of the related D1-silylidyne (SiD; X(2)Pi) acetylene (HCCH; X(1)Sigmag(+)) reaction studied previously in our group, and from there, we discovered that the methyl group acts primarily as a spectator in the title reaction. The formation of 2-methyl-1-silacycloprop-2-enylidene under single-collision conditions via a bimolecular gas-phase reaction augments our knowledge of the hitherto poorly understood silylidyne (SiH; X(2)Pi) radical reactions with small hydrocarbon molecules leading to the synthesis of organosilicon molecules in cold molecular clouds and in carbon-rich circumstellar envelopes. PMID- 26837569 TI - Hetiamacin B-D, new members of amicoumacin group antibiotics isolated from Bacillus subtilis PJS. PMID- 26837570 TI - Persistence Increases in the Absence of the Alarmone Guanosine Tetraphosphate by Reducing Cell Growth. AB - Most bacterial cells are stressed, and as a result, some become tolerant to antibiotics by entering a dormant state known as persistence. The key intracellular metabolite that has been linked to this persister state is guanosine tetraphosphate (ppGpp), the alarmone that was first linked to nutrient stress. In Escherichia coli, ppGpp redirects protein production during nutrient stress by interacting with RNA polymerase directly and by inhibiting several proteins. Consistently, increased levels of ppGpp lead to increased persistence; but, the mechanism by which elevated ppGpp translates into persistence has not been determined. Hence, we explored persistence in the absence of ppGpp so that the underlying mechanism of persister cell formation could be explored. We found that persister cells still form, although at lower levels, in the absence of ppGpp. Additionally, the toxin/antitoxin systems that we investigated (MqsR, MazF, GhoT, and YafQ) remain able to increase persistence dramatically in the absence of ppGpp. By overproducing each E. coli protein from the 4287 plasmid vectors of the ASKA library and selecting for increased persistence in the absence of ppGpp (via a relA spoT mutant), we identified five new proteins, YihS, PntA, YqjE, FocA, and Zur, that increase persistence simply by reducing cell growth. PMID- 26837571 TI - The Citrus transcription factor, CitERF13, regulates citric acid accumulation via a protein-protein interaction with the vacuolar proton pump, CitVHA-c4. AB - Organic acids are essential to fruit flavor. The vacuolar H(+) transporting adenosine triphosphatase (V-ATPase) plays an important role in organic acid transport and accumulation. However, less is known of V-ATPase interacting proteins and their relationship with organic acid accumulation. The relationship between V-ATPase and citric acid was investigated, using the citrus tangerine varieties 'Ordinary Ponkan (OPK)' and an early maturing mutant 'Zaoshu Ponkan (ZPK)'. Five V-ATPase genes (CitVHA) were predicted as important to citric acid accumulation. Among the genes, CitVHA-c4 was observed, using a yeast two-hybrid screen, to interact at the protein level with an ethylene response factor, CitERF13. This was verified using bimolecular fluorescence complementation assays. A similar interaction was also observed between Arabidopsis AtERF017 (a CitERF13 homolog) and AtVHA-c4 (a CitVHA-c4 homolog). A synergistic effect on citric acid levels was observed between V-ATPase proteins and interacting ERFs when analyzed using transient over-expression in tobacco and Arabidopsis mutants. Furthermore, the transcript abundance of CitERF13 was concomitant with CitVHA-c4. CitERF13 or AtERF017 over-expression leads to significant citric acid accumulation. This accumulation was abolished in an AtVHA-c4 mutant background. ERF-VHA interactions appear to be involved in citric acid accumulation, which was observed in both citrus and Arabidopsis. PMID- 26837572 TI - Modeling the combined effect of RNA-binding proteins and microRNAs in post transcriptional regulation. AB - Recent studies show that RNA-binding proteins (RBPs) and microRNAs (miRNAs) function in coordination with each other to control post-transcriptional regulation (PTR). Despite this, the majority of research to date has focused on the regulatory effect of individual RBPs or miRNAs. Here, we mapped both RBP and miRNA binding sites on human 3'UTRs and utilized this collection to better understand PTR. We show that the transcripts that lack competition for HuR binding are destabilized more after HuR depletion. We also confirm this finding for PUM1(2) by measuring genome-wide expression changes following the knockdown of PUM1(2) in HEK293 cells. Next, to find potential cooperative interactions, we identified the pairs of factors whose sites co-localize more often than expected by random chance. Upon examining these results for PUM1(2), we found that transcripts where the sites of PUM1(2) and its interacting miRNA form a stem-loop are more stabilized upon PUM1(2) depletion. Finally, using dinucleotide frequency and counts of regulatory sites as features in a regression model, we achieved an AU-ROC of 0.86 in predicting mRNA half-life in BEAS-2B cells. Altogether, our results suggest that future studies of PTR must consider the combined effects of RBPs and miRNAs, as well as their interactions. PMID- 26837574 TI - G-quadruplex-interacting compounds alter latent DNA replication and episomal persistence of KSHV. AB - Kaposi's sarcoma associated herpesvirus (KSHV) establishes life-long latent infection by persisting as an extra-chromosomal episome in the infected cells and by maintaining its genome in dividing cells. KSHV achieves this by tethering its epigenome to the host chromosome by latency associated nuclear antigen (LANA), which binds in the terminal repeat (TR) region of the viral genome. Sequence analysis of the TR, a GC-rich DNA element, identified several potential Quadruplex G-Rich Sequences (QGRS). Since quadruplexes have the tendency to obstruct DNA replication, we used G-quadruplex stabilizing compounds to examine their effect on latent DNA replication and the persistence of viral episomes. Our results showed that these G-quadruplex stabilizing compounds led to the activation of dormant origins of DNA replication, with preferential bi directional pausing of replications forks moving out of the TR region, implicating the role of the G-rich TR in the perturbation of episomal DNA replication. Over time, treatment with PhenDC3 showed a loss of viral episomes in the infected cells. Overall, these data show that G-quadruplex stabilizing compounds retard the progression of replication forks leading to a reduction in DNA replication and episomal maintenance. These results suggest a potential role for G-quadruplex stabilizers in the treatment of KSHV-associated diseases. PMID- 26837573 TI - Comparative transcriptomics elucidates adaptive phenol tolerance and utilization in lipid-accumulating Rhodococcus opacus PD630. AB - Lignin-derived (e.g. phenolic) compounds can compromise the bioconversion of lignocellulosic biomass to fuels and chemicals due to their toxicity and recalcitrance. The lipid-accumulating bacterium Rhodococcus opacus PD630 has recently emerged as a promising microbial host for lignocellulose conversion to value-added products due to its natural ability to tolerate and utilize phenolics. To gain a better understanding of its phenolic tolerance and utilization mechanisms, we adaptively evolved R. opacus over 40 passages using phenol as its sole carbon source (up to 373% growth improvement over wild-type), and extensively characterized two strains from passages 33 and 40. The two adapted strains showed higher phenol consumption rates (~20 mg/l/h) and ~2-fold higher lipid production from phenol than the wild-type strain. Whole-genome sequencing and comparative transcriptomics identified highly-upregulated degradation pathways and putative transporters for phenol in both adapted strains, highlighting the important linkage between mechanisms of regulated phenol uptake, utilization, and evolved tolerance. Our study shows that the R. opacus mutants are likely to use their transporters to import phenol rather than export them, suggesting a new aromatic tolerance mechanism. The identified tolerance genes and pathways are promising candidates for future metabolic engineering in R. opacus for improved lignin conversion to lipid-based products. PMID- 26837575 TI - The oligomeric architecture of the archaeal exosome is important for processive and efficient RNA degradation. AB - The exosome plays an important role in RNA degradation and processing. In archaea, three Rrp41:Rrp42 heterodimers assemble into a barrel like structure that contains a narrow RNA entrance pore and a lumen that contains three active sites. Here, we demonstrate that this quaternary structure of the exosome is important for efficient RNA degradation. We find that the entrance pore of the barrel is required for nM substrate affinity. This strong interaction is crucial for processive substrate degradation and prevents premature release of the RNA from the enzyme. Using methyl TROSY NMR techniques, we establish that the 3' end of the substrate remains highly flexible inside the lumen. As a result, the RNA jumps between the three active sites that all equally participate in substrate degradation. The RNA jumping rate is, however, much faster than the cleavage rate, indicating that not all active site:substrate encounters result in catalysis. Enzymatic turnover therefore benefits from the confinement of the active sites and substrate in the lumen, which ensures that the RNA is at all times bound to one of the active sites. The evolution of the exosome into a hexameric complex and the optimization of its catalytic efficiency were thus likely co-occurring events. PMID- 26837576 TI - Recurrent chimeric fusion RNAs in non-cancer tissues and cells. AB - Gene fusions and their products (RNA and protein) were once thought to be unique features to cancer. However, chimeric RNAs can also be found in normal cells. Here, we performed, curated and analyzed nearly 300 RNA-Seq libraries covering 30 different non-neoplastic human tissues and cells as well as 15 mouse tissues. A large number of fusion transcripts were found. Most fusions were detected only once, while 291 were seen in more than one sample. We focused on the recurrent fusions and performed RNA and protein level validations on a subset. We characterized these fusions based on various features of the fusions, and their parental genes. They tend to be expressed at higher levels relative to their parental genes than the non-recurrent ones. Over half of the recurrent fusions involve neighboring genes transcribing in the same direction. A few sequence motifs were found enriched close to the fusion junction sites. We performed functional analyses on a few widely expressed fusions, and found that silencing them resulted in dramatic reduction in normal cell growth and/or motility. Most chimeras use canonical splicing sites, thus are likely products of 'intergenic splicing'. We also explored the implications of these non-pathological fusions in cancer and in evolution. PMID- 26837577 TI - Programmable control of bacterial gene expression with the combined CRISPR and antisense RNA system. AB - A central goal of synthetic biology is to implement diverse cellular functions by predictably controlling gene expression. Though research has focused more on protein regulators than RNA regulators, recent advances in our understanding of RNA folding and functions have motivated the use of RNA regulators. RNA regulators provide an advantage because they are easier to design and engineer than protein regulators, potentially have a lower burden on the cell and are highly orthogonal. Here, we combine the CRISPR system from Streptococcus pyogenes and synthetic antisense RNAs (asRNAs) in Escherichia coli strains to repress or derepress a target gene in a programmable manner. Specifically, we demonstrate for the first time that the gene target repressed by the CRISPR system can be derepressed by expressing an asRNA that sequesters a small guide RNA (sgRNA). Furthermore, we demonstrate that tunable levels of derepression can be achieved (up to 95%) by designing asRNAs that target different regions of a sgRNA and by altering the hybridization free energy of the sgRNA-asRNA complex. This new system, which we call the combined CRISPR and asRNA system, can be used to reversibly repress or derepress multiple target genes simultaneously, allowing for rational reprogramming of cellular functions. PMID- 26837578 TI - Isolation of a non-genomic origin fluoroquinolone responsive regulatory element using a combinatorial bioengineering approach. AB - Advances in chemical biology have led to selection of synthetic functional nucleic acids for in vivo applications. Discovery of synthetic nucleic acid regulatory elements has been a long-standing goal of chemical biologists. Availability of vast genome level genetic resources has motivated efforts for discovery and understanding of inducible synthetic genetic regulatory elements. Such elements can lead to custom-design of switches and sensors, oscillators, digital logic evaluators and cell-cell communicators. Here, we describe a simple, robust and universally applicable module for discovery of inducible gene regulatory elements. The distinguishing feature is the use of a toxic peptide as a reporter to suppress the background of unwanted bacterial recombinants. Using this strategy, we show that it is possible to isolate genetic elements of non genomic origin which specifically get activated in the presence of DNA gyrase A inhibitors belonging to fluoroquinolone (FQ) group of chemicals. Further, using a system level genetic resource, we prove that the genetic regulation is exerted through histone-like nucleoid structuring (H-NS) repressor protein. Till date, there are no reports of in vivo selection of non-genomic origin inducible regulatory promoter like elements. Our strategy opens an uncharted route to discover inducible synthetic regulatory elements from biologically-inspired nucleic acid sequences. PMID- 26837582 TI - 2015 FDA drug approvals. PMID- 26837581 TI - Insensitivity to Flaws Leads to Damage Tolerance in Brittle Architected Meta Materials. AB - Cellular solids are instrumental in creating lightweight, strong, and damage tolerant engineering materials. By extending feature size down to the nanoscale, we simultaneously exploit the architecture and material size effects to substantially enhance structural integrity of architected meta-materials. We discovered that hollow-tube alumina nanolattices with 3D kagome geometry that contained pre-fabricated flaws always failed at the same load as the pristine specimens when the ratio of notch length (a) to sample width (w) is no greater than 1/3, with no correlation between failure occurring at or away from the notch. Samples with (a/w) > 0.3, and notch length-to-unit cell size ratios of (a/l) > 5.2, failed at a lower peak loads because of the higher sample compliance when fewer unit cells span the intact region. Finite element simulations show that the failure is governed by purely tensile loading for (a/w) < 0.3 for the same (a/l); bending begins to play a significant role in failure as (a/w) increases. This experimental and computational work demonstrates that the discrete-continuum duality of architected structural meta-materials may give rise to their damage tolerance and insensitivity of failure to the presence of flaws even when made entirely of intrinsically brittle materials. PMID- 26837579 TI - Intracellular mGluR5 plays a critical role in neuropathic pain. AB - Spinal mGluR5 is a key mediator of neuroplasticity underlying persistent pain. Although brain mGluR5 is localized on cell surface and intracellular membranes, neither the presence nor physiological role of spinal intracellular mGluR5 is established. Here we show that in spinal dorsal horn neurons >80% of mGluR5 is intracellular, of which ~60% is located on nuclear membranes, where activation leads to sustained Ca(2+) responses. Nerve injury inducing nociceptive hypersensitivity also increases the expression of nuclear mGluR5 and receptor mediated phosphorylated-ERK1/2, Arc/Arg3.1 and c-fos. Spinal blockade of intracellular mGluR5 reduces neuropathic pain behaviours and signalling molecules, whereas blockade of cell-surface mGluR5 has little effect. Decreasing intracellular glutamate via blocking EAAT-3, mimics the effects of intracellular mGluR5 antagonism. These findings show a direct link between an intracellular GPCR and behavioural expression in vivo. Blockade of intracellular mGluR5 represents a new strategy for the development of effective therapies for persistent pain. PMID- 26837586 TI - Deal watch: Biopharma deal-making in 2015: changing the pharma landscape. PMID- 26837580 TI - Circulating and tumor-infiltrating mucosal associated invariant T (MAIT) cells in colorectal cancer patients. AB - Mucosal associated invariant T (MAIT) cells are important for immune defense against infectious pathogens and regulate the pathogenesis of various inflammatory diseases. However, their roles in the development of colorectal cancer (CRC) are still unclear. This study examined the phenotype, distribution, clinical relevance and potential function of MAIT cells in CRC patients. We found that the percentages of circulating memory CD8(+) MAIT cells were significantly reduced while tumor infiltrating MAIT cells were increased, especially in patients with advanced CRC. The serum CEA levels were positively correlated with the percentages of tumor infiltrating MAIT cells in CRC patients, but negatively correlated with the percentages of circulating MAIT in advanced CRC patients. Activated circulating MAIT cells from CRC patients produced lower IFN-gamma, but higher IL-17. Furthermore, higher levels of Valpha7.2-Jalpha33, IFN-gamma and IL 17A were expressed in the CRC tissues. Co-culture of activated MAIT cells with HCT116 cells enhanced IL-17 expression and induced HCT116 cell cycle arrest at G2/M phase in a contact- and dose-dependent manner, which was abrogated by treatment with anti-MR1. Therefore, MAIT cells preferably infiltrate into the solid tumor in CRC patients and may participate in the immune surveillance of CRC. PMID- 26837587 TI - Michael Hanson. PMID- 26837588 TI - Combination therapies in oncology. PMID- 26837589 TI - Cancer: Mutant p53 rescued by aggregation inhibitor. PMID- 26837593 TI - Target identification: Putting the brakes on preterm labour. PMID- 26837595 TI - Implications of endogenous roles of transporters for drug discovery: hitchhiking and metabolite-likeness. PMID- 26837597 TI - The Effect of Socioeconomic Status Across Adulthood on Trajectories of Frailty in Older Women. AB - BACKGROUND: To investigate whether distinct trajectories of frailty exist in older women and whether they are associated with measures of socioeconomic status (SES) across adulthood. METHODS: Participants were 7484 women born in 1921-1926 from the Australian Longitudinal Study on Women's Health who were surveyed every 3 years from 1999 to 2011. Frailty was measured at each survey using the FRAIL scale. Group-based trajectory modeling was used to assess patterns of frailty. Multinomial logistic regression was used to examine associations of trajectories with SES (level of education, occupation, and ability to manage on income) across adulthood. RESULTS: Three trajectory groups were identified: low (19.5%), increasing (40.7%), and high (39.9%). Compared with women in the increasing frailty group, those who reported difficulty managing on their income in 1999 were less likely to be in the low frailty group (relative risk ratio 0.57, 95% confidence interval 0.39-0.84) and more likely to be in the high frailty group (relative risk ratio 2.65, 95% confidence interval 2.07-3.39), after adjusting for other SES variables, age, and social support. Occupation and education were not associated with trajectories of frailty. CONCLUSIONS: Some women remain frailty free until age 85-90 years. The strongest impact on frailty is late-life SES. PMID- 26837596 TI - Epidermal beta-catenin activation remodels the dermis via paracrine signalling to distinct fibroblast lineages. AB - Sustained epidermal Wnt/beta-catenin signalling expands the stem cell compartment and induces ectopic hair follicles (EFs). This is accompanied by extensive fibroblast proliferation and extracellular matrix (ECM) remodelling in the underlying dermis. Here we show that epidermal Hedgehog (Hh) and Transforming growth factor-beta (TGF-beta) signalling mediate the dermal changes. Pharmacological inhibition or genetic deletion of these pathways prevents beta catenin-induced dermal reprogramming and EF formation. Epidermal Shh stimulates proliferation of the papillary fibroblast lineage, whereas TGF-beta2 controls proliferation, differentiation and ECM production by reticular fibroblasts. Hh inhibitors do not affect TGF-beta target gene expression in reticular fibroblasts, and TGF-beta inhibition does not prevent Hh target gene induction in papillary fibroblasts. However, when Hh signalling is inhibited the reticular dermis does not respond to epidermal beta-catenin activation. We conclude that the dermal response to epidermal Wnt/beta-catenin signalling depends on distinct fibroblast lineages responding to different paracrine signals. PMID- 26837598 TI - Vitamin D status in relation to Crohn's disease: Meta-analysis of observational studies. AB - OBJECTIVES: Inconsistent findings have been published regarding vitamin D status among patients with Crohn's disease (CD) and the association with disease severity. We aimed to perform a meta-analysis evaluating serum 25-hydroxy vitamin D and 1,25 dehydroxyvitamin D among CD patients compared with healthy and non healthy controls, the prevalence of vitamin D deficiency, and the association with disease. METHODS: We searched MEDLINE, SCOPUS, EMBASE, and Google Scholar up to March 2015 for observational studies assessing serum vitamin D levels in CD patients. A total of 63 studies were included in the following four meta analyses: 1) a meta-analysis on the mean difference of 25(OH)D levels in CD patients compared with healthy (number of studies = 27) and non-healthy (n = 25) controls; 2) a meta-analysis on the mean difference of 1,25(OH)2 D3 levels in CD patients compared with healthy (n = 7) and non-healthy (n = 8) controls; 3) a meta-analysis on the prevalence of vitamin D deficiency (n = 34); 4) a meta analysis on the correlation coefficients between vitamin D status severity of CD (n = 6). Subgroup analysis and meta-regression were used to discover possible sources of between-study heterogeneity. RESULTS: It was found that CD patients had lower levels of 25(OH)D compared with healthy (-3.99 ng/mL; 95% confidence interval [CI]: -5.91 to -2.08) but not non-healthy controls (-1.07 ng/mL; 95% CI: -2.84 to 0.70). There was also no significant mean difference for 1,25(OH)2 D3 for both healthy and non-healthy controls. Meta-analysis on the prevalence of vitamin D deficiency showed an overall prevalence of 57.7% (95% CI: 0.502-0.649). An inverse association was observed between serum vitamin D and severity of CD ( 0.36; 95% CI: -0.48 to -0.24). Meta-regression showed that mean levels of 25(OH)D were decreased 0.09 for each unit change of latitude among CD patients compared with healthy controls (B = -0.09, P = 0.004, I(2) residual = 86.08%). CONCLUSIONS: We found that patients with Crohn's disease had lower serum 25(OH)D concentrations compared with their healthy counterparts, and more than half of them have hypovitaminosis D. Moreover, there was an inverse correlation between circulating 25(OH)D concentrations and severity of Crohn's disease. PMID- 26837599 TI - Nicotine may affect the secretion of adipokines leptin, resistin, and visfatin through activation of KATP channel. AB - OBJECTIVE: It has been confirmed that adipokines are associated with atherosclerosis. Cigarette smoking was found to possibly influence adipokine secretion. However, the precise role of smoking in adipokine secretion and the underlying mechanisms are largely unknown. The aim of this study was to determine whether nicotine, the principal active ingredient of cigarettes, can influence adipokine secretion and its potential mechanism. METHODS: The present study consecutively enrolled 96 men, including 50 smokers with early atherosclerosis and 46 nonsmokers. Serum adipokines, including leptin, resistin, and visfatin, were determined with enzyme-linked immunosorbent assay in all participants. Furthermore, the effect of nicotine on secretion of these adipokines was examined in differentiated 3T3-L1 preadipocytes under the conditions of ATP-dependent potassium (KATP) channel blocked or unblocked. RESULTS: Compared with the control group, serum levels of leptin, resistin, and visfatin in smokers were significantly higher. In 3T3-L1 adipocytes, nicotine treatment significantly increased the levels of these adipokines (P = 0.014, 0.001, and 0.029, respectively). When the KATP channel was blocked, secretion of resistin and visfatin was reduced (P < 0.001), but no change was found in the leptin secretion (P = 0.522). CONCLUSIONS: Nicotine may affect the secretion of adipokines leptin, resistin, and visfatin through activation of KATP channel. PMID- 26837600 TI - A Hypersweet Protein: Removal of The Specific Negative Charge at Asp21 Enhances Thaumatin Sweetness. AB - Thaumatin is an intensely sweet-tasting protein that elicits sweet taste at a concentration of 50 nM, a value 100,000 times larger than that of sucrose on a molar basis. Here we attempted to produce a protein with enhanced sweetness by removing negative charges on the interacting side of thaumatin with the taste receptor. We obtained a D21N mutant which, with a threshold value 31 nM is much sweeter than wild type thaumatin and, together with the Y65R mutant of single chain monellin, one of the two sweetest proteins known so far. The complex model between the T1R2-T1R3 sweet receptor and thaumatin, derived from tethered docking in the framework of the wedge model, confirmed that each of the positively charged residues critical for sweetness is close to a receptor residue of opposite charge to yield optimal electrostatic interaction. Furthermore, the distance between D21 and its possible counterpart D433 (located on the T1R2 protomer of the receptor) is safely large to avoid electrostatic repulsion but, at the same time, amenable to a closer approach if D21 is mutated into the corresponding asparagine. These findings clearly confirm the importance of electrostatic potentials in the interaction of thaumatin with the sweet receptor. PMID- 26837601 TI - Multi-Organ toxicity demonstration in a functional human in vitro system composed of four organs. AB - We report on a functional human model to evaluate multi-organ toxicity in a 4 organ system under continuous flow conditions in a serum-free defined medium utilizing a pumpless platform for 14 days. Computer simulations of the platform established flow rates and resultant shear stress within accepted ranges. Viability of the system was demonstrated for 14 days as well as functional activity of cardiac, muscle, neuronal and liver modules. The pharmacological relevance of the integrated modules were evaluated for their response at 7 days to 5 drugs with known side effects after a 48 hour drug treatment regime. The results of all drug treatments were in general agreement with published toxicity results from human and animal data. The presented phenotypic culture model exhibits a multi-organ toxicity response, representing the next generation of in vitro systems, and constitutes a step towards an in vitro "human-on-a-chip" assay for systemic toxicity screening. PMID- 26837603 TI - The barriers and facilitators to evidence-based episiotomy practice in Jordan. AB - AIM: This paper examines the barriers to evidence-based episiotomy practice in Jordan and identifies strategies that may be effective in introducing evidence based practice. BACKGROUND: Episiotomy is routinely undertaken during birth in many parts of the world, including in the Middle East with little scientific evidence of benefit. There is a paucity of research examining the underlying drivers for episiotomy rates, and why they are higher in some countries. METHOD: This study, conducted in Jordan, used a quality improvement approach and comprised three phases. In phase one, a retrospective file review of 300 births was conducted. In phase two, 15 face-to-face interviews were conducted with 10 midwives and five key stakeholders (managers and doctors). A feedback and discussion session using the audit and review model was conducted in phase three with 23 health professionals to identify strategies to reduce the episiotomy rate. RESULTS: The episiotomy rate was 41.4% overall (91% of primiparous women and 24% of multiparous women). Six major themes emerged from the thematic analysis of data: 'Policy: written but invisible and unwritten and assumed'; 'the safest way'; 'doctors set the rules'; 'midwives swimming with the tide; 'uncooperative and uninformed women' and 'the way forward'. CONCLUSIONS: Non evidence based episiotomy practices are widely used during birth in this Jordanian hospital and numerous barriers to change exist. Medical professionals dictate childbirth practice and midwives fear recrimination if they go against the 'unwritten policy'. Strategies to change practice include development of evidence-based information for women, education of midwives and doctors, and policy review. PMID- 26837605 TI - How Can We Make the Health Span Focus of Biomedical Gerontology "Stickier"? PMID- 26837602 TI - Economic evaluation of pediatric influenza immunization program compared with other pediatric immunization programs: A systematic review. AB - This study compared the economic value of pediatric immunisation programmes for influenza to those for rotavirus (RV), meningococcal disease (MD), pneumococcal disease (PD), human papillomavirus (HPV), hepatitis B (Hep B), and varicella reported in recent (2000 onwards) cost-effectiveness (CE) studies identified in a systematic review of PubMed, health technology, and vaccination databases. The systematic review yielded 51 economic evaluation studies of pediatric immunisation - 10 (20%) for influenza and 41 (80%) for the other selected diseases. The quality of the eligible articles was assessed using Drummond's checklist. Although inherent challenges and limitations exist when comparing economic evaluations of immunisation programmes, an overall comparison of the included studies demonstrated cost-effectiveness/cost saving for influenza from a European-Union-Five (EU5) and United States (US) perspective; point estimates for cost/quality-adjusted life-years (QALY) from dominance (cost-saving with more effect) to <=45,444 were reported. The economic value of influenza programmes was comparable to the other vaccines of interest, with cost/QALY in general considerably lower than RV, Hep B, MD and PD. Independent of the perspective and type of analysis, the economic impact of a pediatric influenza immunisation program was influenced by vaccine efficacy, immunisation coverage, costs, and most significantly by herd immunity. This review suggests that pediatric influenza immunisation may offer a cost effective strategy when compared with HPV and varicella and possibly more value compared with other childhood vaccines (RV, Hep B, MD and PD). PMID- 26837604 TI - Does eating oily fish improve gestational and neonatal outcomes? Findings from a Sicilian study. AB - BACKGROUND: Fish is a source of long-chain polyunsaturated n-3 fatty acids, but it may also contain a number of pollutants. METHODS: Between April and July 2013, we selected 114 women who gave birth to living babies, and divided them according to type and frequency of the fish consumed. We evaluated both gestational and neonatal outcomes. Docosahexaenoic acid (DHA) supplementation was taken into account. FINDINGS: One hundred and four women (91.2%) consumed fish on the average of 4.7 times/month, while 10 (8.8%) did not consume fish at all. Fifty nine women (51.8%) were taking supplements containing DHA (200mg/day), almost all of whom (n=55) consumed fish. Pregnancy induced hypertension was more frequent in non-fish eaters than in fish eaters (20% vs 4.8%, P=0.056). Consumption of small size oily fish correlated positively with both neonatal weight (r=0.195, P=0.037) and head circumference (r=0.211, P=0.024). In contrast, consumption of lean fish or shellfish correlated negatively with neonatal head circumference (r=0.206, P=0.028, or r=0.192, P=0.041). DISCUSSION: These data agree with previous observational studies and reinforce the protective role of small oily fish consumption on preterm birth risk, neonatal weight, length and head circumference. CONCLUSION: Small oily fish consumption should be favored over other types of fish. PMID- 26837606 TI - Exploiting the CRISPR/Cas9 System for Targeted Genome Mutagenesis in Petunia. AB - Recently, CRISPR/Cas9 technology has emerged as a powerful approach for targeted genome modification in eukaryotic organisms from yeast to human cell lines. Its successful application in several plant species promises enormous potential for basic and applied plant research. However, extensive studies are still needed to assess this system in other important plant species, to broaden its fields of application and to improve methods. Here we showed that the CRISPR/Cas9 system is efficient in petunia (Petunia hybrid), an important ornamental plant and a model for comparative research. When PDS was used as target gene, transgenic shoot lines with albino phenotype accounted for 55.6%-87.5% of the total regenerated T0 Basta-resistant lines. A homozygous deletion close to 1 kb in length can be readily generated and identified in the first generation. A sequential transformation strategy--introducing Cas9 and sgRNA expression cassettes sequentially into petunia--can be used to make targeted mutations with short indels or chromosomal fragment deletions. Our results present a new plant species amenable to CRIPR/Cas9 technology and provide an alternative procedure for its exploitation. PMID- 26837608 TI - Orphan immunotherapies for allergic diseases. AB - OBJECTIVE: As confirmed by systematic reviews and meta-analyses, allergen immunotherapy is clinically effective in the treatment of allergic diseases. In particular, subcutaneous immunotherapy is a pivotal treatment in patients with severe reactions to Hymenoptera venom, whereas subcutaneous immunotherapy and sublingual immunotherapy are indicated in the treatment of allergic rhinitis and asthma by inhalant allergens. Other allergies related to animal dander (other than cat, which is the most studied), such as dog, molds, occupational allergens, and insects, have also been recognized. For these allergens, immunotherapy is poorly studied and often unavailable. Thus, use of the term orphan immunotherapies is appropriate. DATA SOURCES: We used MEDLINE to search the medical literature for English-language articles. STUDY SELECTION: Randomized, controlled, masked studies for orphan immunotherapies were selected. In the remaining cases, the available reports were described. RESULTS: The literature on food desensitization is abundant, but for other orphan allergens, such as mosquito, Argas reflexus, dog, or occupational allergens, there are only a few studies, and most are small studies or case reports. CONCLUSION: Orphan immunotherapy is associated with insufficient evidence of efficacy from controlled trials, an erroneous belief of the limited importance of some allergen sources, and the unlikelihood for producers to have a profit in making commercially available extracts (with an expensive process for registration) to be used in few patients. It should be taken into consideration that adequate preparations should be available also for orphan allergens. PMID- 26837607 TI - Exploring racial differences in IgE-mediated food allergy in the WHEALS birth cohort. AB - BACKGROUND: Suspected food allergies are the cause of more than 200,000 visits to the emergency department annually. Racial differences in the prevalence of food allergy have also been reported, but the evidence is less conclusive. Researchers continue to struggle with the identification of food allergy for epidemiologic studies. OBJECTIVE: To explore racial differences in IgE-mediated food allergy (IgE-FA) in a birth cohort. METHODS: We used a panel of board-certified allergists to systematically identify IgE-FA to egg, milk, or peanut in a multiethnic birth cohort in which patient medical history, patient symptoms, and clinical data were available through 36 months of age. RESULTS: Of the 590 infants analyzed, 52.9% were male and 65.8% African American. Sensitization (serum specific IgE >0.35 IU/mL) to the food allergens was significantly higher for African American children compared with non-African American children as has been previously reported. No statistically significant racial/ethnic differences in IgE-FA were observed; however, a higher proportion of African American children were designated as having peanut allergy, and the percentage of African American children with an IgE level greater than 95% predictive decision points for peanut was 1.7% vs 0.5% for non-African American children. With the use of logistic regression, race/ethnicity was not significantly associated with IgE-FA (adjusted odds ratio, 1.12; 95% confidence interval, 0.58-2.17; P = .75) but was associated with sensitization to more than 1 of the food allergens (adjusted odds ratio, 1.80; 95% confidence interval, 1.22-2.65; P = .003). CONCLUSION: We did not observe an elevated risk of IgE-FA for African American children, although established differences in sensitization were observed. Racial/ethnic differences in sensitization must be taken into consideration when investigating disparities in asthma and allergy. PMID- 26837609 TI - Chemical partitioning and antioxidant capacity of green coffee (Coffea arabica and Coffea canephora) of different geographical origin. AB - Green coffee beans of Coffea arabica and Coffea canephora accessions from different geographical origin (Brazil, Colombia, Ethiopia, Honduras, Kenya, Mexico, Peru, Uganda and Vietnam) were extracted and the extracts analyzed by HPLC-ESI-MS/MS for the identification and quantification of chlorogenic acids and caffeine content. Principal component and cluster analyses were used to identify chemical patterns separating the different species and accessions based on their geographical origin. C. canephora showed always a higher caffeine content with respect to C. arabica, whereas the C. arabica accessions from Kenya showed a higher chlorogenic acids and a lower caffeine content. The antioxidant capacity of green coffee extracts was assayed by the reducing power and DPPH assays. The antioxidant capacity correlated with the chlorogenic acids content. The results show that the C. arabica from Kenya possesses the highest chlorogenic acids/caffeine ratio and, among the C. arabica accessions, the highest antioxidant capacity. Therefore, the C. arabica from Kenya is the most suitable green coffee source for nutraceutical applications because of its high antioxidant capacity and low caffeine content. PMID- 26837610 TI - The effects of N-acetyl-L-cysteine on the female reproductive performance and nephrotoxicity in rats. AB - This study was designed to investigate whether the treatment with the N-acetyl-L cysteine prior to the administration of chemotherapy drug would prevent from nephrotoxicity and the loss of reproductive performance induced from chemotherapy treatment. Female rats were divided into five equal groups of six each: 1/control group; 2/rats i.p administered saline solution; 3/rats i.p administered holoxan (50 mg/kg b.wt); 4/rats i.p administered N-acetyl-L-cysteine (160 mg/kg b.wt); 5/rats i.p administered holoxan and N-acetyl-L-cysteine at the same doses. After medications, females rats were allowed to mate with males and the pregnant rats were sacrificed on day 18 of gestation. Premating treatment with holoxan showed reduction (p < 0.05) in reproductive performance. Whereas administration of N acetyl-L-cysteine prior to treatment with holoxan and then concurrently with it modulated significantly fertility index, progesterone level, decreasing postimplantation loss, resorbed fetuses and improved fetal growth. Additionally, holoxan elevated the renal nicotinamide dinucleotide phosphate (NADPH) oxidase activity, oxidative stress, renal functions and caused histological changes in renal tissue. N-Acetyl-L-cysteine treatment reduced (p < 0.05) renal tissue NADPH oxidase, nitric oxide, malondialdehyde and improved super oxide dismutase (SOD) depletion, elevated levels phosphate, total protein and calcium as well as prevented renal histological damages. N-Acetyl-L-cysteine can confer protection against nitrosative and oxidative stresses in renal tissue induced by holoxan by suppressing NADPH oxidase activation, malondialdehyde, nitric oxide and restoring SOD activity which led to the reduction of reactive oxygen species production and subsequently might effectively improve the gonadal hormone disturbance and reproductive functions. PMID- 26837611 TI - Defining Swallowing-Related Quality of Life Profiles in Individuals with Amyotrophic Lateral Sclerosis. AB - Although it is known that dysphagia contributes to significant malnutrition, pneumonia, and mortality in amyotrophic lateral sclerosis (ALS), it remains unclear how swallowing impairment impacts quality of life in this vulnerable patient population. The aim of the current study was to (1) delineate swallow related quality of life (SR-QOL) profiles in individuals with ALS and (2) evaluate relationships between SR-QOL, degree of swallowing impairment, and ALS global disease progression. Eighty-one ALS patients underwent a standardized videofluoroscopic swallow study and completed the swallowing quality of life (SWAL-QOL) instrument and ALS functional rating scale-revised (ALSFRS-R). Penetration Aspiration Scale (PAS) scores were derived by a blinded rater. Correlation analyses and a between groups ANOVA (safe vs. penetrators vs. aspirators) were performed. Mean SWAL-QOL score for this cohort was 75.94 indicating a moderate degree of SR-QOL impairment with fatigue, eating duration, and communication representing the most affected domains. Correlations were revealed between the SWAL-QOL and (1) PAS (r = -0.39, p < 0.001) and (2) ALSFRS-R (r = 0.23, p < 0.05). Mean (SD) SWAL-QOL scores for safe versus penetrator versus aspirator groups were 81.2 (2.3) versus 77 (3.4) versus 58.7 (5.9), respectively, with a main effect observed [F(2,78) = 9.71, p < 0.001]. Post hoc testing revealed lower SWAL-QOL scores for aspirators versus safe swallowers (p < 0.001) and aspirators versus penetrators (p < 0.001). Overall, SR-QOL was moderately reduced in this cohort of ALS patients and profoundly impacted in ALS aspirators and individuals with advanced disease. These findings highlight the importance of early multidisciplinary intervention to not only avoid malnutrition, weight loss, and pulmonary sequelae but also the associated reduced QOL seen in these individuals. PMID- 26837612 TI - Evaluating the Training Effects of Two Swallowing Rehabilitation Therapies Using Surface Electromyography--Chin Tuck Against Resistance (CTAR) Exercise and the Shaker Exercise. AB - In this study, the efficacy of two dysphagia interventions, the Chin Tuck against Resistance (CTAR) and Shaker exercises, were evaluated based on two principles in exercise science-muscle-specificity and training intensity. Both exercises were developed to strengthen the suprahyoid muscles, whose contractions facilitate the opening of the upper esophageal sphincter, thereby improving bolus transfer. Thirty-nine healthy adults performed two trials of both exercises in counter balanced order. Surface electromyography (sEMG) recordings were simultaneously collected from suprahyoid muscle group and sternocleidomastoid muscle during the exercises. Converging results using sEMG amplitude analyses suggested that the CTAR was more specific in targeting the suprahyoid muscles than the Shaker exercise. Fatigue analyses on sEMG signals further indicated that the suprahyoid muscle group were equally or significantly fatigued (depending on metric), when participants carried out CTAR compared to the Shaker exercise. Importantly, unlike during Shaker exercise, the sternocleidomastoid muscles were significantly less activated and fatigued during CTAR. Lowering the chin against resistance is therefore sufficiently specific and intense to fatigue the suprahyoid muscles. PMID- 26837615 TI - Erratum to: The neurological and ophthalmological manifestations of SPG4-related hereditary spastic paraplegia. PMID- 26837614 TI - The association between maternal-reported responses to infant crying at 4 weeks and 6 months and offspring depression at 18: a longitudinal study. AB - The purpose of the present study is to examine the association between maternal response to infant crying and the psychological health of the child in later life. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, consisting of 15,247 pregnancies, 10,278 with exposure variables and 3201 complete cases were identified as having exposure, covariate and outcome data. Using a postal questionnaire, mothers were asked regarding their infant at 4 weeks and 6 months, 'If they cry what do you do?': (a) pick them up immediately; (b) if they cry, leave them for a while, and if they do not stop, pick them up; or (c) never pick them up until you are ready. Outcome was an International Statistical Classification-10th revision criteria (ICD-10) diagnosis of depression at 18 years for the infant. Offspring of mothers who at 4 weeks reported that they never picked their infants up until they were ready were more likely to have depression at 18 years (OR = 2.06, CI 0.95-4.47, adjusted for sociodemographic confounding variables). There was no evidence for an association at 6 months. Including adjustment variables reduced the strength of our association; an observed objective measure of maternal response rather than a self-report may have more accurately determined the mother's actual responses. There is some evidence for an association between maternal reporting of responses to infant crying at 4 weeks and risk of developing depression at 18 years. If this association is found to be causal, interventions encouraging mothers to represent and respond to their infants' emotional states may help prevent offspring depression. PMID- 26837616 TI - Multiplex cytokine analyses in dogs with pyometra suggest involvement of KC-like chemokine in canine bacterial sepsis. AB - Clinical diagnostic criteria for sepsis (systemic inflammatory response syndrome caused by infection) are unspecific and, therefore, biomarkers for sepsis diagnosis are needed for appropriate treatment and patient survival. Pyometra, a common disease caused by bacterial infection of the uterus, results in sepsis in nearly 60% of cases in dogs. We used dogs with pyometra as a natural model for sepsis and collected serum samples from 39 dogs, of which 22 with pyometra and 17 healthy controls. Dogs with pyometra were further grouped into dogs with sepsis (n=18) and without sepsis (n=4). Serum concentrations of a panel of cytokines, including keratinocyte-derived chemokine (KC)-like, granulocyte-macrophages colony stimulating factor (GM-CSF), interleukin (IL)-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, chemokine C-X-C motif ligand (CXCL)10 and tumor necrosis factor (TNF)-alpha, were measured using multiplex analyses. Serum C-reactive protein (CRP) levels were determined using an automated immunoturbidimetric assay. In addition to physical examination hematological and serum biochemical analyses were performed to evaluate the overall status of the dogs. Significantly higher concentrations of KC-like (757 vs 304 pg/ml) were detected in dogs with pyometra as compared to healthy dogs. Within the pyometra group, dogs with sepsis compared to dogs without sepsis had a higher KC-like concentration (873 vs 300 pg/ml). Hemoglobin levels were significantly lower in dogs with pyometra compared to healthy dogs, regardless of the presence or absence of sepsis, and correlated negatively with KC-like. KC-like concentrations correlated positively with CRP, number of hospitalization days, number of monocytes, concentrations of IL-8, and percentage band neutrophils. Our data suggest that bacterial infection triggers the expression of KC-like and further studies are warranted of KC-like as a possible biomarker for diagnosing sepsis and uterine bacterial infection in dogs. PMID- 26837617 TI - Urban Stormwater Governance: The Need for a Paradigm Shift. AB - Traditional urban stormwater management involves rapid removal of stormwater through centralized conveyance systems of curb-gutter-pipe networks. This results in many adverse impacts on the environment including hydrological disruption, groundwater depletion, downstream flooding, receiving water quality degradation, channel erosion, and stream ecosystem damage. In order to mitigate these adverse impacts, urban stormwater managers are increasingly using green infrastructure that promote on-site infiltration, restore hydrological functions of the landscape, and reduce surface runoff. Existing stormwater governance, however, is centralized and structured to support the conventional systems. This governance approach is not suited to the emerging distributed management approach, which involves multiple stakeholders including parcel owners, government agencies, and non-governmental organizations. This incongruence between technology and governance calls for a paradigm shift in the governance from centralized and technocratic to distributed and participatory governance. This paper evaluates how five US cities have been adjusting their governance to address the discord. Finally, the paper proposes an alternative governance model, which provides a mechanism to involve stakeholders and implement distributed green infrastructure under an integrative framework. PMID- 26837618 TI - Abnormalities in the Structure and Function of Cerebellar Neurons and Neuroglia in the Lc/+ Chimeric Mouse Model of Variable Developmental Purkinje Cell Loss. AB - Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by impaired and disordered language, decreased social interactions, stereotyped and repetitive behaviors, and impaired fine and gross motor skills. It has been well established that cerebellar abnormalities are one of the most common structural changes seen in the brains of people diagnosed with autism. Common cerebellar pathology observed in autistic individuals includes variable loss of cerebellar Purkinje cells (PCs) and increased numbers of reactive neuroglia in the cerebellum and cortical brain regions. The Lc/+ mutant mouse loses 100 % of cerebellar PCs during the first few weeks of life and provided a valuable model to study the effects of developmental PC loss on underlying structural and functional changes in cerebellar neural circuits. Lurcher (Lc) chimeric mice were also generated to explore the link between variable cerebellar pathology and subsequent changes in the structure and function of cerebellar neurons and neuroglia. Chimeras with the most severe cerebellar pathology (as quantified by cerebellar PC counts) had the largest changes in cFos expression (an indirect reporter of neural activity) in cerebellar granule cells (GCs) and cerebellar nucleus (CN) neurons. In addition, Lc chimeras with the fewest PCs also had numerous reactive microglia and Bergmann glia located in the cerebellar cortex. Structural and functional abnormalities observed in the cerebella of Lc chimeras appeared to be along a continuum, with the degree of pathology related to the number of PCs in individual chimeras. PMID- 26837619 TI - Morphological characterization and immunohistochemical detection of the proinflammatory cytokines IL-1beta, IL-17A, and TNF-alpha in lung lesions associated with contagious bovine pleuropneumonia. AB - Contagious bovine pleuropneumonia (CBPP), a severe respiratory disease, is characterized by massive inflammation of the lung especially during the acute clinical stage of infection. Tissue samples from cattle, experimentally infected with Mycoplasma mycoides subsp. mycoides Afade, were subjected to histopathological and immunohistochemical examination in order to provide insight into innate immune pathways that shape inflammatory host responses. Lung lesions were characterized by vasculitis, necrosis, and increased presence of macrophages and neutrophils, relative to uninfected animals. The presence of three cytokines associated with innate inflammatory immune responses, namely, IL-1beta, IL-17A, and TNF-alpha, were qualitatively investigated in situ. Higher cytokine levels were detected in lung tissue samples from CBPP-affected cattle compared to samples derived from an uninfected control group. We therefore conclude that the cytokines TNF-alpha and IL-1beta, which are prevalent in the acute phase of infections, play a role in the inflammatory response seen in the lung tissue in CBPP. IL-17A gets released by activated macrophages and attracts granulocytes that modulate the acute phase of the CBPP lesions. PMID- 26837621 TI - Movement and Orientation Decision Modeling of Rhyzopertha dominica (Coleoptera: Bostrichidae) in the Grain Mass. AB - Grain stored in bins is initially a relatively homogenous resource patch for stored-product insects, but over time, spatial pattern in insect distribution can form, due in part to insect movement patterns. However, the factors that influence stored-product insect movement patterns in grain are not well understood. This research focused on the movement of the lesser grain borer, Rhyzopertha dominica (F.), within a simulated wheat grain mass (vertical monolayer of wheat) and the identification of factors that contribute to overall and upward movement (age since adult emergence from an infested kernel [1, 7, and 14 d], sex, strain, and different levels of environment quality). We also used the model selection approach to select the most relevant factors and determine the relationships among them. Three-week-old adults tended to stay closer to the surface compared with 1- or 2-wk-old insects. Also, females tended to be more active and to explore a larger area compared with males. Explored area and daily displacement were also significantly strain-dependent, and increasing grain infestation level decreased daily displacement and explored area. Variation in movement pattern is likely to influence the formation of spatial pattern and affect probability to disperse. Understanding movement behavior within a grain bin is crucial to designing better strategies to implement and interpret monitoring programs and to target control tactics. PMID- 26837620 TI - Specific binding of a naturally occurring amyloidogenic fragment of Streptococcus mutans adhesin P1 to intact P1 on the cell surface characterized by solid state NMR spectroscopy. AB - The P1 adhesin (aka Antigen I/II or PAc) of the cariogenic bacterium Streptococcus mutans is a cell surface-localized protein involved in sucrose independent adhesion and colonization of the tooth surface. The immunoreactive and adhesive properties of S. mutans suggest an unusual functional quaternary ultrastructure comprised of intact P1 covalently attached to the cell wall and interacting with non-covalently associated proteolytic fragments thereof, particularly the ~57-kDa C-terminal fragment C123 previously identified as Antigen II. S. mutans is capable of amyloid formation when grown in a biofilm and P1 is among its amyloidogenic proteins. The C123 fragment of P1 readily forms amyloid fibers in vitro suggesting it may play a role in the formation of functional amyloid during biofilm development. Using wild-type and P1-deficient strains of S. mutans, we demonstrate that solid state NMR (ssNMR) spectroscopy can be used to (1) globally characterize cell walls isolated from a Gram-positive bacterium and (2) characterize the specific binding of heterologously expressed, isotopically-enriched C123 to cell wall-anchored P1. Our results lay the groundwork for future high-resolution characterization of the C123/P1 ultrastructure and subsequent steps in biofilm formation via ssNMR spectroscopy, and they support an emerging model of S. mutans colonization whereby quaternary P1-C123 interactions confer adhesive properties important to binding to immobilized human salivary agglutinin. PMID- 26837622 TI - Prognostic value of a pre-freeze hypo-osmotic swelling test on the post-thaw quality of dog semen. AB - Throughout cryopreservation, sperm are exposed to major osmotic challenges. Only intact membranes of sperm cells are able to regulate these volumetric changes, which can be determined by the hypo-osmotic swelling test (HOS test). Correlations between the HOS test and conventional semen variables are inconsistent. Therefore, the objectives of this study were (1) to examine relationships between HOS test results and standard semen variables before freezing and after thawing and (2) to evaluate the prognostic value of the HOS assessments on post-thaw quality of dog semen. Semen of 35 dogs was collected and analyzed before freezing and after thawing following a 7-day freeze-thaw interval. Conventional semen variables such as sperm cell motility, membrane integrity morphology were evaluated and the HOS test was conducted with results from this test being recorded. In fresh semen the HOS test was positively correlated with progressive motility of sperm cells: r=0.52, sperm cell membrane integrity: r=0.50 and normal sperm cell morphology: r=0.46 (P<0.05). In frozen thawed semen, the data obtained with the HOS test were positively correlated with progressive sperm cell motility: r=0.67 and membrane integrity: r=0.86 (P<0.05). The data obtained with the HOS test in fresh semen were positively correlated with sperm cell membrane integrity: r=0.50 normal sperm cell morphology: r=0.55 and data from the HOS test (r=0.43; P<0.05) with frozen-thawed semen. For the prediction of individual cryopreservation capacity, results from assessment of the fresh semen variables of good and poor semen quality were statistically compared. Based on these results, it is not possible to predict the quality of frozen-thawed dog semen using the HOS test. PMID- 26837623 TI - Recent Tobacco Smoking is Associated with Poor HIV Medical Outcomes Among HIV Infected Individuals in New York. AB - Tobacco smoking is associated with adverse health effects among people living with HIV (PLWH), including a higher risk of cancer and cardiovascular problems. Further, there is evidence that PLWH are two to three times more likely to smoke than the general population. The aim of this study was to examine the association between tobacco smoking and biomarkers of HIV disease progression, including unsuppressed viral load (viral load >200 copies/mL) and low CD4 cell count (<200 cells/mm(3)). Recent tobacco smoking was reported by 40 % (n = 5942) of 14,713 PLWH enrolled in Ryan White Part A programs in the New York City metropolitan area. In multivariate analyses controlling for sociodemographic and clinical characteristics, recent tobacco smoking was independently associated with unsuppressed viral load (AOR = 1.38, CI 1.26-1.50) and low CD4 cell count (AOR = 1.12, CI 1.01-1.24). Findings suggest the importance of routine assessments of tobacco use in clinical care settings for PLWH. PMID- 26837625 TI - Internalized HIV Stigma and Disclosure Concerns: Development and Validation of Two Scales in Spanish-Speaking Populations. AB - Internalized stigma and disclosure concerns are key elements for the study of mental health in people living with HIV. Since no measures of these constructs were available for Spanish population, this study sought to develop such instruments, to analyze their reliability and validity and to provide a short version. A heterogeneous sample of 458 adults from different Spanish-speaking countries completed the HIV-Internalized Stigma Scale and the HIV-Disclosure Concerns Scale, along with the Hospital Anxiety and Depression Scale, Rosenberg's Self-esteem Scale and other socio-demographic variables. Reliability and correlation analyses, exploratory factor analyses, path analyses with latent variables, and ANOVAs were conducted to test the scales' psychometric properties. The scales showed good reliability in terms of internal consistency and temporal stability, as well as good sensitivity and factorial and criterion validity. The HIV-Internalized Stigma Scale and the HIV-Disclosure Concerns Scale are reliable and valid means to assess these variables in several contexts. PMID- 26837624 TI - Feasibility of Using Soccer and Job Training to Prevent Drug Abuse and HIV. AB - Many young, South African men use alcohol and drugs and have multiple partners, but avoid health care settings-the primary site for delivery of HIV intervention activities. To identify the feasibility of engaging men in HIV testing and reducing substance use with soccer and vocational training programs. In two Cape Town neighborhoods, all unemployed men aged 18-25 years were recruited and randomized by neighborhood to: (1) an immediate intervention condition with access to a soccer program, random rapid diagnostic tests (RDT) for alcohol and drug use, and an opportunity to enter a vocational training program (n = 72); or (2) a delayed control condition (n = 70). Young men were assessed at baseline and 6 months later by an independent team. Almost all young men in the two neighborhoods participated (98 %); 85 % attended at least one practice (M = 42.3, SD = 34.4); 71 % typically attended practice. Access to job training was provided to the 35 young men with the most on-time arrivals at practice, drug-free RDT, and no red cards for violence. The percentage of young men agreeing to complete RDT at soccer increased significantly over time; RDTs with evidence of alcohol and drug use decreased over time. At the pre-post assessments, the frequency of substance use decreased; and employment and income increased in the immediate condition compared to the delayed condition. HIV testing rates, health care contacts, sexual behaviors, HIV knowledge, condom use and attitudes towards women were similar over time. Alternative engagement strategies are critical pathways to prevent HIV among young men. This feasibility study shows that soccer and job training offer such an alternative, and suggest that a more robust evaluation of this intervention strategy be pursued. PMID- 26837626 TI - Unmet HIV Service Needs Among Hispanic Men who Have Sex with Men in the United States. AB - The National HIV/AIDS Strategy (NHAS) originally issued in 2010 targets the reduction of HIV-related health disparities. Hispanic men who have sex with men (MSM) have the third highest burden of incident HIV in the US, but there are no estimates of the unmet HIV service needs for Hispanic MSM. We estimate that of approximately 204,800 Hispanic MSM living with HIV, roughly 46,900 were undiagnosed. 157,900 were diagnosed, and of those, 75,700 were not linked to care and 82,200 were linked. Among diagnosed individuals, 48,800 had undetectable viral loads, and 109,100 had detectable viral loads. An estimated 30,000 of diagnosed Hispanic MSM engage in unprotected, serodiscordant risk behaviors. Total cost to meet service needs and achieve NHAS goals is ~$2.511 billion in 2011 US dollars. Transmission rate modeling suggests this investment would avert 3656 new HIV infections at an economically favorable cost of $61,202 per quality adjusted life year saved. PMID- 26837627 TI - Effects of In-country and Cross-Border Mobility on Condom Use Among Transgender Women (hijras) in Bangladesh: A Cross-Sectional Study. AB - In Bangladesh transgender women (hijras) are thought to be highly mobile that may be an impediment to condom use. This cross-sectional study was conducted to determine the extent of mobility of hijras, in-country and cross-border, and whether mobility affects condom use in anal intercourse. Hijras >=15 years of age, receiving services from the Global Fund supported HIV prevention program were enrolled. A behavioral questionnaire was administered and blood was tested for antibodies to HIV and syphilis. Of 889 hijras sampled, 41.3 % never traveled, 26.4 % traveled in-country and 32.3 % crossed the border in the last year. HIV and active syphilis was at 0.8 and 1.8 % respectively. Among hijras who crossed the border condom use was less likely in last anal intercourse (AOR 0.68; 95 % CI 0.48-0.96), and consistently with new (AOR 0.59; 95 % CI 0.34-1.01) and regular clients (AOR 0.45; 95 % CI 0.27-0.76) in the last week. This study concludes that in Bangladesh hijras are highly mobile and cross-border mobility negatively affects condom use. PMID- 26837628 TI - Adherence and Acceptability of a Multidrug Vaginal Ring for HIV Prevention in a Phase I Study in the United States. AB - We evaluated the adherence and acceptability of a vaginal ring containing dapivirine, maraviroc, or both drugs for 28 days during a Phase I placebo controlled trial in 48 HIV-negative sexually abstinent U.S. women aged 18-40. Adherence was assessed weekly by clinical interview and computer-assisted self interviewing; acceptability assessment occurred at the last product-use visit. Study retention was 98 % (47/48); 94 % (45/48) reported being fully adherent with ring use during the 28-day period. Two participants experienced the ring partially coming out. Analysis was blinded and behavioral data were combined across study groups. Most women reported being very comfortable having the ring in their vagina; 44 % preferred continuous use, whereas 51 % had no preference compared to episodic use. Although a range of minor ring concerns were expressed, few were actually experienced. High adherence to and acceptability of this vaginal ring in this Phase I trial contributes to its promise as a sustained mechanism for multidrug vaginal microbicide delivery. PMID- 26837629 TI - The Feasibility and Acceptability of Using Technology-Based Daily Diaries with HIV-Infected Young Men Who have Sex with Men: A Comparison of Internet and Voice Modalities. AB - This study delivered a daily diary to 67 HIV-infected men who have sex with men (MSM) between 16 and 24 years old for 66 days to measure HIV-risk behaviors and other psychosocial variables via two diary modalities: internet (accessible via any web-enabled device) and voice (accessible via telephone). Participants were randomized to complete one diary modality for 33 days before switching to the second modality for 33 days. The study was implemented in three urban HIV health care centers in the United States where participants were receiving services. Through diary data and qualitative interview data, we examined the feasibility and acceptability of the dairies and identified barriers and facilitators of dairy compliance. Results show high participant retention in the daily diary (93.4 %) and high compliance for the number of dairies completed (72.4 %). Internet diaries were preferred by 92 % of participants and completed at a significantly higher rate (77.5 %) than voice diaries (67.7 %). Facilitators included opportunities for self-reflection and cathartic sharing, monetary compensation, relationships with study staff, and daily reminders. Barriers included being busy or not having privacy at the time of reminders, forgetting, and falling asleep. Participants also described barriers and facilitators unique to each modality. Overall, both modalities were feasible and acceptable for use with our sample of HIV-infected MSM. PMID- 26837630 TI - Improving Engagement in the HIV Care Cascade: A Systematic Review of Interventions Involving People Living with HIV/AIDS as Peers. AB - Improving patient engagement in HIV care is critical for maximizing the impact of antiretroviral therapy (ART). We conducted a systematic review of studies that used HIV-positive peers to bolster linkage, retention, and/or adherence to ART. We searched articles published and indexed in Pubmed, PsycINFO, and CINAHL between 1996 and 2014. Peers were required to be HIV-positive. Studies were restricted to those published in English. Nine studies with n = 4658 participants met the inclusion criteria. Peer-based interventions were predominantly focused on improving adherence to ART, or evaluations of retention and adherence via viral suppression. Five (56 %) were conducted in sub-Saharan Africa. Overall findings were mixed on the impact of peers on ART adherence, viral suppression, and mortality. While positive effects of peer interventions on improving linkage and retention were found, there were limited studies assessing these outcomes. Additional research is warranted to demonstrate the impact of peers on linkage and retention in diverse populations. PMID- 26837632 TI - Does Integrating Family Planning into HIV Services Improve Gender Equitable Attitudes? Results from a Cluster Randomized Trial in Nyanza, Kenya. AB - This study investigated whether integrating family planning (FP) services into HIV care was associated with gender equitable attitudes among HIV-positive adults in western Kenya. Surveys were conducted with 480 women and 480 men obtaining HIV services from 18 clinics 1 year after the sites were randomized to integrated FP/HIV services (N = 12) or standard referral for FP (N = 6). We used multivariable regression, with generalized estimating equations to account for clustering, to assess whether gender attitudes (range 0-12) were associated with integrated care and with contraceptive use. Men at intervention sites had stronger gender equitable attitudes than those at control sites (adjusted mean difference in scores = 0.89, 95 % CI 0.03-1.74). Among women, attitudes did not differ by study arm. Gender equitable attitudes were not associated with contraceptive use among men (AOR = 1.06, 95 % CI 0.93-1.21) or women (AOR = 1.03, 95 % CI 0.94-1.13). Further work is needed to understand how integrating FP into HIV care affects gender relations, and how improved gender equity among men might be leveraged to improve contraceptive use and other reproductive health outcomes. PMID- 26837631 TI - Examining the Efficacy of HIV Risk-Reduction Counseling on the Sexual Risk Behaviors of a National Sample of Drug Abuse Treatment Clients: Analysis of Subgroups. AB - HIV counseling with testing has been part of HIV prevention in the U.S. since the 1980s. Despite the long-standing history of HIV testing with prevention counseling, the CDC released HIV testing recommendations for health care settings contesting benefits of prevention counseling with testing in reducing sexual risk behaviors among HIV-negatives in 2006. Efficacy of brief HIV risk-reduction counseling (RRC) in decreasing sexual risk among subgroups of substance use treatment clients was examined using multi-site RCT data. Interaction tests between RRC and subgroups were performed; multivariable regression evaluated the relationship between RRC (with rapid testing) and sex risk. Subgroups were defined by demographics, risk type and level, attitudes/perceptions, and behavioral history. There was an effect (p < .0028) of counseling on number of sex partners among some subgroups. Certain subgroups may benefit from HIV RRC; this should be examined in studies with larger sample sizes, designed to assess the specific subgroup(s). PMID- 26837633 TI - Anxiety and Depressive Symptoms Among People Living with HIV and Childhood Sexual Abuse: The Role of Shame and Posttraumatic Growth. AB - There is a critical need to examine protective and risk factors of anxiety and depressive symptoms among people living with HIV in order to improve quality of life. Structural equation modeling was used to examine the associations between HIV-related shame, sexual abuse-related shame, posttraumatic growth, and anxiety and depressive symptoms among a cohort of 225 heterosexual women and men who have sex with men (MSM) living with HIV who have experienced childhood sexual abuse (CSA). Higher sexual abuse-related shame was related to more anxiety and depressive symptoms for heterosexual women. Higher posttraumatic growth predicted less anxiety symptoms for only heterosexual women. Higher posttraumatic growth predicted less depressive symptoms for heterosexual women and MSM, but the magnitude of this effect was stronger for heterosexual women than MSM. Psychosocial interventions may need to be tailored to meet the specific needs of heterosexual women and MSM living with HIV and CSA. PMID- 26837636 TI - Quantitative Reconstructions of 3D Chemical Nanostructures in Nanowires. AB - Energy dispersive X-ray spectrometry is used to extract a quantitative 3D composition profile of heterostructured nanowires. The analysis of hypermaps recorded along a limited number of projections, with a preliminary calibration of the signal associated with each element, is compared to the intensity profiles calculated for a model structure with successive shells of circular, elliptic, or faceted cross sections. This discrete tomographic technique is applied to II-VI nanowires grown by molecular beam epitaxy, incorporating ZnTe and CdTe and their alloys with Mn and Mg, with typical size down to a few nanometers and Mn or Mg content as low as 10%. PMID- 26837634 TI - HIV Testing Behavior and Social Network Characteristics and Functions Among Young Men Who have Sex with Men (YMSM) in Metropolitan Detroit. AB - HIV testing promotion is a critical HIV prevention strategy, especially among at risk groups such as young men who have sex with men (YMSM). Based on a web survey of 194 YMSM (18-24), we examine the association of social network characteristics and functions, and of individual-level characteristics, with three HIV testing behaviors (ever, repeat, and recent testing). Network homophily was associated with recent testing in multivariable models. The network function of information acquisition was associated with ever testing and repeat testing. Perceived stigma regarding HIV-related help-seeking was negatively related to recent testing. Individual characteristics were associated with testing outcomes in all models; age, perceived behavioral control, and positive attitudes had the greatest influence. Individual characteristics had a stronger association with ever testing and repeat testing than network characteristics and functions; however, this relationship was reversed for recent testing. Findings support the value of multi-level and network-focused interventions for promoting HIV testing among YMSM. PMID- 26837635 TI - Patterns of Drug Use and Drug-related Hospital Admissions in HIV-Positive and Negative Gay and Bisexual Men. AB - We aimed to compare rates of illicit drug-related hospitalisations in HIV negative (HIV-ve) (n = 1325) and HIV-positive (HIV+ve) (n = 557) gay and bisexual men (GBM) with rates seen in the general male population and to examine the association between self-reported illicit drug use and drug-related hospitalisation. Participants were asked how often they used a range of illicit drugs in the previous 6 months at annual interviews. Drug-related hospital admissions were defined as hospital admissions for mental or behavioural disorders due to illicit drug use (ICD 10: F11-16, F18, F19), drug poisoning (T40 T45, T50) or toxic effect of gases (T53, T59, T65). Drug-related hospitalisations were 4.8 times higher in the HIV-ve cohort [SIR 4.75 (95 % CI 3.30-6.91)] and 3.5 times higher in the HIV+ve cohort [SIR 3.51 (1.92-5.88)] compared with the general population. Periods of weekly drug use [IRR 1.86 (1.01-3.46)], poly-drug use [IRR 2.17 (1.07-4.38)] and cannabis use [low use-IRR 1.95 (1.01-3.77), high use-IRR 2.58 (1.29-5.16)] were associated with drug-related hospitalisation in both cohorts, as was being a consistently high meth/amphetamine user throughout follow-up [IRR 3.24 (1.07-9.83)] and being an inconsistent or consistent injecting drug user throughout follow-up [IRR 3.94 (1.61-9.66), IRR 4.43(1.04 18.76), respectively]. Other risk factors for drug-related hospitalisation indicated the likelihood of comorbid drug and mental health issues in GBM hospitalised for drug use. PMID- 26837637 TI - Stylomandibular fusion complicating recurrent bilateral temporomandibular joint ankylosis. AB - Ankylosis of the temporomandibular joint (TMJ) is debilitating, and difficult to manage because it recurs. Recurrent bilateral ankylosis is further complicated by the fusion of the styloid process and the mandible. We report such a case, and to our knowledge no similar case has been reported previously. PMID- 26837638 TI - Tumour seeding after fine-needle aspiration and core biopsy of the head and neck- a systematic review. AB - Although fine-needle aspiration cytology (FNAC) and core needle biopsy are essential diagnostic investigations of lumps in the head and neck, seeding along the needle track has long been a concern, and various factors have been implicated. We therefore searched the Medline database for relevant English language papers published between 1970 and 2014, excluding those on the thyroid and parathyroid, and systematically reviewed them to assess the risk. In the 610 articles reviewed we found only 7 reports of seeding (5 after FNAC and 2 after core needle biopsy). Tumours were found between 3 months and 3 years after the procedure in 4 cases, and in 3, tumour cells were found along the needle track between 0 and 33 days after the procedure. The needles varied in size from 18 - 22 gauge (G) and there were 3 to 4 passes. Four cases occurred after investigation of a mass in the salivary glands, and 3 after assessment of a cervical lymph node. Disease was benign in one and malignant in 6. Seeding along the needle track after FNAC or core needle biopsy of a lump in the head and neck is rarely reported, and an accurate estimate of its incidence is difficult to ascertain. Crude estimates suggest 0.00012% and 0.0011% after FNA and core needle biopsy, respectively. A distinction should be made between seeding that is seen shortly after the procedure and the development of tumour along the needle track. PMID- 26837639 TI - Endoscopic mucosal resection of large non-ampullary duodenal polyps: technical aspects and long-term therapeutic outcomes. AB - BACKGROUND: Our aim was to evaluate the efficacy, safety and long term outcomes of endoscopic mucosal resection (EMR) of large non-ampullary duodenal polyps. METHODS: A retrospective review of patients undergoing EMR of non-ampullary duodenal polyps >= 10 mm in size was performed. EMR was performed using standard snare polypectomy using pure coagulation current. Patient demographics, polyp site and histopathology, resection technique, use of adjunctive argon plasma coagulation (APC) ablation, adverse events, and residual/recurrent neoplasia at follow-up were evaluated. RESULTS: 59 duodenal lesions were removed by EMR (mean age 62 years, 55.9% men). 17 (28.8%) polyps were located in the bulb, 31 (50.8%) in the 2nd portion and 12 (20.3%) in the 3rd part of the duodenum. The mean size of lesions resected was. Submucosal saline injection followed by hot snare polypectomy was performed for 29 (49%) endoscopies. Adjunctive ablation of focal residual neoplastic tissue with APC was applied in 18 cases (30.5%). Complete endoscopic eradication during a single session was performed successfully in 46 (79%) patients. En-bloc resection was performed in 40 polyps (67%) and piecemeal resection in 19 (32.2%). Procedure complications were acute bleeding (N.=11) and 1 microperforation that was managed with clip closure and antibiotics. The mean follow-up time was 37 months (range 22-53). The overall endoscopic cure rate was 93%. On follow-up surveillance, residual adenoma was identified in 13 (22%) patients; these were all eradicated endoscopically. CONCLUSIONS: EMR for large non-ampullary duodenal adenomas is a safe and effective technique to achieve complete eradication. PMID- 26837640 TI - Uninformed guidelines for mechanical in-exsufflation. PMID- 26837642 TI - Recovery of rhodium with a novel soft donor ligand using solvent extraction techniques in chloride media. AB - Rhodium remains a high value platinum group metal that has key applications in electronics, catalysts, and batteries. To provide a useful tool for Rh isolation, a novel tridentate ligand utilizing soft N and S donors was designed to specifically extract Rh. The synthesis, complexation kinetics, and liquid-liquid extraction studies were performed to explore the overall process and recovery of Rh from chloride media. PMID- 26837641 TI - Influence of age on clinical outcomes of three-dimensional transfer of the tibial tuberosity for patellar instability with patella alta. AB - PURPOSE: To evaluate the clinical outcomes of three-dimensional (3D) transfer of the tibial tuberosity for patellar instability with patella alta, with a focus on the influence of age at initial surgery. METHODS: Three-dimensional surgery was performed on 28 knees with a mean follow-up of 46 months. Patients were separated into three groups based on the age at initial surgery: group A, 10 knees and an average age of 16.3 +/- 1.8 (14-19) years; group B, 10 knees and an average age of 22.1 +/- 2.5 (20-28) years; and group C, eight knees and an average age of 44.0 +/- 2.2 (40-46) years. Patellofemoral geometry improvement focused on patella alta by determining the Insall-Salvati ratio and Caton-Deschamps index, rotational malalignment by measuring the tibial tubercle-trochlear groove (TT-TG) distance, and lateral patellar subluxation by measuring the patellar tilt. Clinical outcomes were evaluated by the Lysholm and Kujala scores, which were compared before and after surgery. Cartilage degeneration was evaluated by the International Cartilage Repair Society grading system at initial arthroscopy. RESULTS: The patellar height, TT-TG, and patellar tilt significantly improved in all groups postoperatively (p < 0.05). The Lysholm and Kujala scores also significantly improved postoperatively; however, both scores were lower in group C than in the other groups (p < 0.05). Particularly, pain scores were more severe in group C than in the other groups, and the severity of cartilage degeneration correlated with the pain scores (p < 0.05). Cartilage damage differed significantly between the groups at initial arthroscopy; particularly, group C included grades III and IV cartilage degeneration (p < 0.05). CONCLUSIONS: Age at initial surgery may be the predicting factor for poor clinical outcomes of 3D transfer surgery. The clinical outcome may depend on the age at surgery, which correlated with cartilage damage; thus, surgeons should be given this information when patients are considered undergoing patella surgery. LEVEL OF EVIDENCE: Therapeutic case series, Level IV. PMID- 26837644 TI - Soft Tissue Pseudosarcomas. AB - Soft tissue pathology is one of the most challenging areas of diagnostic pathology, not only because of the morphologic diversity of such lesions, but also because of their rarity and pathologists' subsequent lack of exposure to these tumors. Many lesions mimic malignant mesenchymal neoplasms, collectively referred to as "pseudosarcomas." The list of proliferations that can simulate a sarcoma is extensive and heterogeneous. This review addresses malignant, nonmesenchymal neoplasms; mesenchymal neoplasms that histologically mimic sarcomas but are benign; and benign reactive soft tissue lesions that are neither neoplastic nor malignant, but have worrisome clinical and/or morphologic features. PMID- 26837643 TI - High Short-Term Blood Pressure Variability Predicts Long-Term Cardiovascular Mortality in Untreated Hypertensives But Not in Normotensives. AB - BACKGROUND: The prognostic value of the short-term blood pressure variability (BPV) from the 24-hour ambulatory blood pressure monitoring (ABPM) remains controversial. The present study aimed to investigate the long-term prognostic value of a high BPV in normotensive and hypertensive subjects from a community based population. METHODS: A cohort of 624 normotensive and 633 untreated hypertensive Taiwanese participants (overall 669 men, aged 30-79 years) with baseline ABPM and 20-year all-cause and cardiovascular mortality data was drawn from a community-based survey. BPV was assessed by the read-to-read average real variability of the 24-hour diastolic and systolic blood pressure (SBP) (ARVd and ARVs, respectively). RESULTS: In Cox proportional hazards analysis, ARVd predicted cardiovascular mortality independently of office SBP (hazard ratios (HRs) and 95% confidence intervals (CIs) per 1 SD: 1.31 (1.10-1.55), respectively, bivariate analysis), 24-hour SBP (HR: 1.19, 95% CI: 1.00-1.43), and conventional risk factors (age, sex, smoking, total cholesterol, high-density lipoprotein cholesterol, and fasting blood glucose, HR: 1.40, 95% CI: 1.18-1.67). In subjects with hypertension, a high vs. low ARVd (median: 8.8mm Hg) significantly predicted cardiovascular mortality (HR: 2.11, 95% CI: 1.23-3.62 and HR: 2.04, 95% CI: 1.19-3.51, respectively), when the conventional risk factors plus office SBP or 24-hour SBP were accounted for, respectively. Similar but less significant results were obtained with ARVs. A high ARVd or ARVs did not significantly predict cardiovascular mortality in the normotensive subjects. CONCLUSIONS: A high short-term BPV is significantly predictive of long-term cardiovascular mortality in untreated hypertensive but not normotensive community based subjects, independently of office or 24-hour SBP. PMID- 26837645 TI - Spindle Cell Sarcomas. AB - Information is presented on the pathology of spindle cell sarcomas. Synovial sarcoma, malignant peripheral nerve sheath tumor, fibrosarcoma, inflammatory myofibroblastic tumor, low-grade myofibrosarcoma, leiomyosarcoma, spindle cell rhabdomyosarcoma, and endothelial neoplasms are discussed in terms of an overview of the tumor, microscopic and gross features, diagnostic techniques, genetic markers, differential diagnosis, clinical details, and prognosis. PMID- 26837646 TI - Myofibroma, Myopericytoma, Myoepithelioma, and Myofibroblastoma of Skin and Soft Tissue. AB - The authors address a group of loosely associated, characteristically benign soft tissue neoplasms that exhibit partial myoid differentiation. The entities share similarities in morphology and in nomenclature that have historically created confusion. The authors attempt to clarify the distinct architectural patterns and the corresponding immunophenotypic and ultrastructural features that distinguish myofibroma, myopericytoma, myoepithelioma, and myofibroblastoma. PMID- 26837647 TI - Peripheral Nerve Sheath Tumors. AB - This article presents an overview of the diagnostic categories of benign and malignant nerve sheath tumors, including neuroma, neurofibroma, nerve sheath myxoma, perineurioma, schwannoma, and malignant peripheral nerve sheath tumor. The discussion emphasizes histologic patterns; ancillary studies, such as immunohistochemistry; and differential diagnoses. The information is of value to practicing pathologists in both community and academic settings. PMID- 26837648 TI - Clear Cell Tumors of Soft Tissue. AB - Clear cell lesions of soft tissue include varying morphologic patterns and a range of clinical behaviors and prognoses. Benign lesions include perivascular epithelioid cell tumors, clear cell fibrous papule, and distinctive dermal clear cell mesenchymal tumor; malignant tumors include clear cell sarcoma, liposarcoma, and rare malignant perivascular epithelioid cell tumors. Clear cell variants of other benign and malignant soft tissue tumors include fibrous histiocytoma, atypical fibroxanthoma, myoepithelioma, leiomyoma and leiomyosarcoma, and rhabdomyosarcoma. Metastatic clear cell tumors, including renal cell carcinoma and adrenal cortical carcinoma, should be considered in the differential diagnosis and excluded through clinical history, imaging studies, and immunohistochemical stains. PMID- 26837649 TI - Primitive Round Cell Neoplasms. AB - Primitive round cell neoplasms (small round cell tumors) of soft tissue are a diverse group of malignant tumors composed of monotonous undifferentiated cells with high nuclear-cytoplasmic ratio. Many occur more frequently, although not exclusively, in childhood. As tumors with primitive round cell morphology are seen in virtually every basic tumor category, the diagnosis of small round cell neoplasms requires the use of ancillary diagnostic techniques: immunohistochemistry and often molecular genetics. The principal tumors in this group include Ewing sarcoma/primitive neuroectodermal tumor, desmoplastic small round cell tumor, alveolar rhabdomyosarcoma, poorly differentiated synovial sarcoma, neuroblastoma, and ganglioneuroblastoma. PMID- 26837650 TI - Dermal and Subcutaneous Plexiform Soft Tissue Neoplasms. AB - This article presents an overview of soft tissue tumors that have a plexiform histomorphology. The more commonly encountered entities, including plexiform fibrohistiocytic tumor, cellular neurothekeoma, dermal nerve sheath myxoma, plexiform schwannoma, and plexiform neurofibroma, are discussed in detail, and other tumors are noted. Information on clinical features, microscopic findings, ancillary studies, differential diagnosis, and prognosis is provided for each entity. PMID- 26837651 TI - Myxoid Neoplasms. AB - Myxoid tumors of soft tissue constitute a heterogeneous group of neoplasms characterized by the presence of a myxoid stromal matrix, which appears on H&E as an amorphous material and may be confused with edema. Superficial myxoid lesions in general are benign and deep ones are malignant. Grossly, they have a variable gelatinous quality and overlapping histologic features that may present diagnostic difficulties for pathologists. Most are sporadic neoplasms, with only a small percentage arising in patients with hereditary disorders. Discussed are key features of classic myxoid lesions, histologic features, characteristic clinical presentations, immunohistochemical patterns, cytogenetic analysis, and differential diagnosis. PMID- 26837652 TI - Epithelioid Lesions. AB - Epithelioid variants have been described for most mesenchymal tumors, including leiomyosarcoma, pleomorphic liposarcoma, epithelioid fibrous histiocytoma, and myxofibrosarcoma. Soft tissue tumors that commonly show epithelioid morphology include epithelioid vascular lesions, epithelioid sarcoma, sclerosing epithelioid fibrosarcoma, and epithelioid malignant peripheral nerve sheath tumor. Many of the entities described in this review were originally described as "simulating carcinoma" or "often mistaken for carcinoma" and this pitfall should be considered when evaluating epithelioid lesions in soft tissue. Many epithelioid soft tissue tumors express epithelial antigens to a varying degree and an immunohistochemical panel is essential for correct classification. PMID- 26837653 TI - Selected Lesions Featuring Giant Cells. AB - Many neoplasms of the soft tissues feature giant cells, but this article covers entities in which giant cells are a striking feature. Specifically, we consider tenosynovial giant cell tumor (localized and diffuse types; giant cell tumor of tendon sheath, and pigmented villonodular tenosynovitis), reticulohistiocytoma, juvenile xanthogranuloma, giant cell fibroblastoma (a variant form of dermatofibrosarcoma protuberans), giant cell angiofibroma (which is essentially a giant cell-rich form of solitary fibrous tumor), and phosphaturic mesenchymal tumor. PMID- 26837654 TI - Gastrointestinal Tract Mesenchymal Lesions. AB - This article reviews the most common and characteristic mesenchymal lesions found in the gastrointestinal tract and intraabdominal location in a pattern-based approach: spindle and epithelioid tumors (gastrointestinal stromal tumor, schwannoma, glomus tumor, leiomyoma and leiomyosarcoma, inflammatory fibroid polyp, perineurioma, melanoma, calcifying fibrous tumor, sclerosing mesenteritis, mesenteric fibromatosis, and inflammatory myofibroblastic tumor), and clear and granular tumors (clear cell sarcoma, granular cell tumor, gangliocytic paraganglioma, and ganglioneuroma). Information includes gross and histologic features, diagnosis and differential diagnosis, and histologic and other diagnostic techniques, including immunohistochemistry related to projected patient outcome, along with prognosis, staging, and treatment. PMID- 26837655 TI - Liposarcomas. AB - Liposarcoma is a common soft tissue sarcoma and represents a group of neoplasms, each with distinct clinical behavior and pathologic findings. Proper classification is critical for clinical management and prognostication. Until recently, immunohistochemistry played a limited role in diagnosis of these tumors. Increased understanding of the underlying genetic basis of disease has paved the way for development of improved tools for diagnosis and new forms of targeted therapy. This article summarizes the clinical, pathologic, and molecular findings of the main liposarcoma subtypes. Special attention to the differential diagnosis and difficulties the pathologist may face when interpreting these lesions is discussed. PMID- 26837656 TI - Pattern Approach to Soft Tissue Tumors. PMID- 26837657 TI - Tuning the Band Gap of Cu2ZnSn(S,Se)4 Thin Films via Lithium Alloying. AB - Alkali metal doping plays a crucial role in fabricating high-performance Cu(In,Ga)(S,Se)2 and Cu2ZnSn(S,Se)4 (CZTSSe) thin film solar cells. In this study, we report the first experimental observation and characterizations of the alloyed Li(x)Cu(2-x)ZnSn(S,Se)4 thin films. It is found that Cu(+) ions in Cu2ZnSn(S,Se)4 thin films can be substituted with Li(+) ions, forming homogeneous Li(x)Cu(2-x)ZnSn(S,Se)4 (0 <= x <= 0.29) alloyed thin films. Consequently, the band gap, conduction band minimum, and valence band maximum of Li(x)Cu(2 x)ZnSn(S,Se)4 thin films are profoundly affected by Li/Cu ratios. The band alignment at the Li(x)Cu(2-x)ZnSn(S,Se)4/CdS interface can be tuned by changing the Li/Cu ratio. We found that the photovoltaic parameters of the Li(x)Cu(2 x)ZnSn(S,Se)4 solar cell devices are strongly influenced by the Li/Cu ratios. Besides, the lattice constant, carrier concentration, and crystal growth of Li(x)Cu(2-x)ZnSn(S,Se)4 thin films were studied in detail. PMID- 26837658 TI - Copper-catalyzed decarboxylative cross-coupling of cinnamic acids and ACCN via single electron transfer. AB - A novel and convenient method for the synthesis of beta,gamma-unsaturated nitriles using ACCN (1,1'-azobis(cyclohexane-1-carbonitrile)) as a cyano source was described. This reaction was amenable to a broad range of substrates and provided the desired beta,gamma-unsaturated nitriles containing an all-carbon quaternary carbon center in moderate yields with high selectivity via single electron transfer and decarboxylation. PMID- 26837659 TI - Quantitative analysis of powdered caffeine products purchased from the Internet using liquid chromatography-quadrupole time-of-flight mass spectrometry. AB - CONTEXT: Powdered caffeine is sold on the Internet as a supplement. Severe toxicity and fatalities have been reported with use, but it is unclear if this toxicity was due to excessive dosing, mislabeled products, or adulterant stimulants. Our objective was to analyze the contents of commercially available powdered caffeine products in order to assess product purity and presence of additional ingredients, contaminants, or adulterants which may contribute to toxicity. METHODS: A sample of nine powdered caffeine products was purchased from the Internet. Two sample replicates of each caffeine product were analyzed. Liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) was used to identify and quantify substances in the purchased products and purity of the compounds were calculated. RESULTS: Comparison of actual mass versus labeled mass of caffeine demonstrated a mean purity of 88.25% (SD 13.41%) and median purity of 90.1%. The products studied contained 1.6-5.3 g per teaspoon. Labeling on these products had limited instructions regarding how to measure the recommended dose. CONCLUSIONS: Powdered caffeine products that are readily available on the Internet contained relatively pure caffeine with no additional detected stimulants. High purity, small serving size, and lack of clear dosing instructions may place users at risk of toxicity. PMID- 26837660 TI - Ertapenem therapy for pneumonia requiring hospital admission in elderly people. AB - OBJECTIVE: Few studies examined ertapenem for the treatment of pneumonia. This study aims to compare ertapenem with other antibiotics commonly used for the treatment of pneumonia requiring hospital admission in elderly patients in daily clinical practice. METHODS: We conducted an observational, retrospective case control study,between January 2011 and January 2014, in a university hospital. Patients >=65 years of age admitted to the hospital with pneumonia treated with ertapenem were included as cases. A control patient treated with antibiotics other than ertapenem, matched for age and pneumonia severity index (PSI), was enrolled for each case. Hospital mortality was the primary outcome. RESULTS: A total of 150 patients with a mean age of 84.1 years were studied. Ninety percent of patients had pneumonia PSI grade IV-V and 82.7% had one or more comorbidities. Healthcare-associated pneumonia (HCAP) and aspiration pneumonia were significantly higher in the ertapenem group (66.7% vs. 24.0%, p < 0.001 and 73.3% vs. 54.7%, p < 0.017, respectively), whereas malignancy was most common in the control group. There was no difference in the hospital mortality rate between ertapenem and control groups (20.0% vs. 20.0%, p = 0.500), after adjusting for HCAP, aspiration pneumonia and malignancy. Transfer from hospital to hospital at home was significantly higher in the ertapenem group (25.3% vs. 9.3%, p = 0.09). CONCLUSIONS: Ertapenem is as effective as other antibiotics commonly used for the treatment of pneumonia requiring hospital admission in elderly people. Ertapenem is associated with a higher transfer to hospital at home. PMID- 26837662 TI - On the origin and magnitude of surface stresses due to metal nanofilms. AB - Metallisation is a vital process for micro- and nanofabrication, allowing the controlled preparation of material surfaces with thin films of a variety of metals. The films are often subjected to further processing, including etching, patterning, chemical modification, and additional lamination. The extensive applications of metallised substrates include chemical sensors and nanoelectronics. Here, we report an experimental study of the metallisation of silicon cantilevers with nano-films of chromium and titanium. Analysis of the stress distribution throughout the cantilever showed that metallisation causes a constant stress along the length of the beam, which can be calculated from interferometric quantification of the beam curvature. The structure of the metal/silicon interface was imaged using electron microscopy in an attempt to ascertain the physical origin of the stress. A theoretical model is constructed for the stressed beam system, and it is shown that there is no single parameter that can describe the change in stress. The resultant structure after deposition varies significantly for each metal, which gives rise to a variety of stress directions and magnitudes. PMID- 26837661 TI - The effect of congruence in patient and therapist alliance on patient's symptomatic levels. AB - OBJECTIVE: The ability of alliance to predict outcome has been widely demonstrated, but less is known about the effect of the level of congruence between patient and therapist alliance ratings on outcome. In the current study we examined whether the degree of congruence between patient and therapist alliance ratings can predict symptomatic levels 1 month later in treatment. METHOD: The sample consisted of 127 patient-therapist dyads. Patients and therapists reported on their alliance levels, and patients reported their symptomatic levels 1 month later. Polynomial regression and response surface analysis were used to examine congruence. RESULTS: Findings suggest that when the congruence level of patient and therapist alliance ratings was not taken into account, only the therapist's alliance served as a significant predictor of symptomatic levels. But when the degree of congruence between patient and therapist alliance ratings was considered, the degree of congruence was a significant predictor of symptomatic levels 1 month later in treatment. CONCLUSIONS: Findings support the importance of the level of congruence between patient and therapist alliance ratings in predicting patient's symptomatic levels. PMID- 26837663 TI - Hyperbranched polymer mediated size-controlled synthesis of gadolinium phosphate nanoparticles: colloidal properties and particle size-dependence on MRI relaxivity. AB - Hyperbranched polymers based on the poly(amidoamine), HyPAM, were used to synthesize gadolinium phosphate nanowires under mild conditions. Control of the average particle size was obtained by adjusting polymer concentration. Proton relaxivity measurements reveal an optimum particle size, reaching relaxivity values as high as 55 +/- 9 mM(-1) s(-1) for r1 and 67 +/- 11 mM(-1) s(-1) for r2. The colloidal stability of these hybrid systems were optimized through the use of functionalized core-shell polymers containing PEG segments and C18-PEG segments, structures which also offer the possibility of imparting additional function into the polymer-particle hybrids. PMID- 26837664 TI - New Chelators for Low Temperature Al(18)F-Labeling of Biomolecules. AB - The Al(18)F labeling method is a relatively new approach that allows radiofluorination of biomolecules such as peptides and proteins in a one-step procedure and in aqueous solution. However, the chelation of the {Al(18)F}(2+) core with the macrocyclic chelators NOTA or NODA requires heating to 100-120 degrees C. Therefore, we have developed new polydentate ligands for the complexation of {Al(18)F}(2+) with good radiochemical yields at a temperature of 40 degrees C. The stability of the new Al(18)F-complexes was tested in phosphate buffered saline (PBS) at pH 7.4 and in rat serum. The stability of the Al(18)F-L3 complex was found to be comparable to that of the previously reported Al(18)F NODA complex up to 60 min in rat serum. Moreover, the biodistribution of Al(18)F L3 in healthy mice showed the absence of in vivo defluorination since no significant bone uptake was observed, whereas the major fraction of activity at 60 min p.i. was observed in liver and intestines, indicating hepatobiliary clearance of the radiolabeled ligand. The acyclic chelator H3L3 proved to be a good lead candidate for labeling of heat-sensitive biomolecules with fluorine-18. In order to obtain a better understanding of the different factors influencing the formation and stability of the complex, we carried out more in-depth experiments with ligand H3L3. As a proof of concept, we successfully conjugated the new AlF-chelator with the urea-based PSMA inhibitor Glu-NH-CO-NH-Lys to form Glu-NH-CO-NH-Lys(Ahx)L3, and a biodistribution study in healthy mice was performed with the Al(18)F-labeled construct. This new class of AlF-chelators may have a great impact on PET radiochemical space as it will stimulate the rapid development of new fluorine-18 labeled peptides and other heat-sensitive biomolecules. PMID- 26837665 TI - Survival outcomes after surgical resection of pulmonary metastases of head and neck tumours. AB - BACKGROUND: There is limited information available regarding the benefits and outcomes of resection of pulmonary metastases arising from head and neck cancers. METHODS: A retrospective review was performed of 21 patients who underwent resection of pulmonary metastases of primary head and neck malignancies at Hamamatsu University Hospital. Clinical staging, treatment methods, pathological subtype (particularly squamous cell carcinoma), disease-free interval and overall survival were evaluated. RESULTS: The 5- and 10-year overall survival rates of the study participants were 67.0 per cent and 55.0 per cent, respectively, as determined by the Kaplan-Meier method. The prognosis for patients with a disease free interval of less than 24 months was poor compared to those with a disease free interval of greater than 24 months (p = 0.0234). CONCLUSION: Patients with short disease-free intervals, and possibly those who are older than 60 years, should be categorised as having severe disease. However, pulmonary metastases from head and neck malignancies are potentially curable by surgical resection. PMID- 26837666 TI - Electric dipole moments and chemical bonding of diatomic alkali-alkaline earth molecules. AB - We investigate the properties of alkali-alkaline earth diatomic molecules in the lowest Sigma(+) states of the doublet and quartet multiplicity by ab initio calculations. In all sixteen cases studied, the permanent electric dipole moment points in opposite directions for the two spin states. This peculiarity can be explained by molecular orbital theory. We further discuss dissociation energies and bond distances. We analyze trends and provide an empirically motivated model for the prediction of the permanent electric dipole moment for combinations of alkali and alkaline earth atoms not studied in this work. PMID- 26837667 TI - Demyelinating disorders secondary to TNF-inhibitor therapy for the treatment of psoriasis: A review. AB - BACKGROUND: Tumor necrosis factor-alpha inhibitors (TNFi) are the most widely used systemic treatments for patients with psoriasis and psoriatic arthritis. There currently exists a U.S. Food and Drug Administration issued warning label on all TNFi for "rare cases of new onset or exacerbation of central nervous system demyelinating disorders." The aim of this review was to update the incidence of TNFi-induced demyelinating diseases. METHODS: Pubmed database was searched for safety data regarding demyelinating disease secondary to TNFi therapy prescribed for psoriasis. RESULTS: In clinical trials: 6990 patients had received treatment with etanercept with one reported case of multiple sclerosis; 5204 patients were treated with adalimumab with no cases identified and 2322 patients were treated with infliximab with one case of demyelinating polyneuropathy. Outside of clinical trials: 19 individual cases of demyelinating disorders from TNFi treatment have been reported. CONCLUSION: Although there is potential for TNF blockade to lead to demyelination of the central and peripheral nervous systems, the results of the present review suggest that demyelinating diseases associated with TNFi are extremely rare. TNFi are not recommended for use in patients with a personal history of demyelinating disease. However, with clinical vigilance and individualized treatment regimen, TNFi may be safe for use in other patients. PMID- 26837668 TI - Cancer incidence and mortality among the Metis population of Alberta, Canada. AB - BACKGROUND: Cancer has been identified as a major cause of morbidity and mortality in Canada over the last decade. However, there is a paucity of information about cancer patterns in Aboriginal people, particularly for Metis. This study aims to explore cancer incidence and mortality burden among Metis and to compare disease estimates with non-Metis population. METHODS: This population based descriptive epidemiological study used cancer incidence and mortality data from 2007 to 2012 obtained from Alberta Health Care Insurance Plan (AHCIP) - Central Stakeholder Registry - and Alberta Cancer Registry (ACR). To identify cancer cases in Metis, the ACR was linked with the Metis Nation of Alberta (MNA) Identification Registry. In Metis and non-Metis people, age-standardized cancer incidence and mortality rates were estimated and subsequently compared between both groups. RESULTS: A higher incidence of bronchus/lung cancer was found among Metis men compared with their non-Metis counterparts (RR=1.69, CI 1.28-2.09; p=0.01). No other statistically significant differences in cancer incidence or mortality were found between Metis and non-Metis people living in Alberta over the course of the 6 years studied. CONCLUSIONS: Overall incidence and mortality associated with cancer were not higher among Metis people compared with non-Metis people. However, special efforts should be considered to decrease the higher incidence of bronchus/lung cancer in Metis men. Further development and maintenance of new and existing institutional collaborations are necessary to continue cancer research and health status surveillance in Metis population. PMID- 26837669 TI - Basal cell adenoma of the parotid gland; MR features and differentiation from pleomorphic adenoma. AB - OBJECTIVES: Among the benign tumours of the parotid gland, basal cell adenoma (BCA) is far less common than pleomorphic adenoma (PA). MR features of BCA, including diffusion-weighted imaging and dynamic contrast-enhanced study, have not been previously described. Assessment of the crucial MR features of BCA appears to offer beneficial clues for distinguishing BCA from PA. METHODS: We retrospectively reviewed 14 BCAs and 179 PAs in the parotid gland, collected between March 2000 and May 2012, from the MRI database. RESULTS: Nearly half of the BCAs had cystic components. The average ratio of the maximum diameter of the cysts to the BCAs (cystic ratio) was 0.80 +/- 0.11 [standard deviation (SD)]. The BCA cystic ratio was significantly higher (p = 0.00232) than that of PAs. The cystic ratio threshold was 0.65 between cystic BCA and cystic PA. Sensitivity and specificity were 76.5% and 100%, respectively. The average of the apparent diffusion coefficient (ADC) values of the 12 BCAs [1.24 +/- 0.18 (SD) *10(-3) mm(2) s(-1)] was significantly lower than that of the 151 PAs [1.86 +/- 0.40 (SD) *10(-3) mm(2) s(-1)] (p < 0.001) and also lower than that of the cystic PAs [1.83 +/- 0.57 (SD) *10(-3) mm(2) s(-1)] (p < 0.00495). The ADC threshold was 1.31 * 10(-3) mm(2) s(-1) between BCA and cystic PA, with sensitivity and specificity of 81.2% and 91.7%, respectively, and also the same threshold 1.31 * 10(-3) mm(2) s( 1) between BCA and PA, with sensitivity and specificity of 92.7% and 91.7%, respectively. Time-signal intensity curves (TICs) showed various patterns. CONCLUSIONS: A small cystic mass with well-circumscribed borders and slightly lower ADC value may suggest BCA, although TICs showed various patterns. PMID- 26837670 TI - Utilization of computer-aided detection system in diagnosing unilateral maxillary sinusitis on panoramic radiographs. AB - OBJECTIVES: It is unclear whether computer-aided detection (CAD) systems for panoramic radiography can help inexperienced dentists to diagnose maxillary sinusitis. The aim of this study was to clarify whether a CAD system for panoramic radiography can contribute to improved diagnostic performance for maxillary sinusitis by inexperienced dentists. METHODS: The panoramic radiographs of 49 patients with maxillary sinusitis and 49 patients with healthy sinuses were evaluated in this study. The diagnostic performance of the CAD system was determined. 12 inexperienced dentists and 4 expert oral and maxillofacial radiologists observed the total of 98 panoramic radiographs and judged the presence or absence of maxillary sinusitis, under conditions with and without the support of the CAD system. The receiver operating characteristic curves of the two groups were compared. RESULTS: The CAD system provided sensitivity of 77.6%, specificity of 69.4% and accuracy of 73.5%. The diagnostic performance of the inexperienced dentists increased with the support of the CAD system. When the inexperienced dentists diagnosed maxillary sinusitis with CAD support, the area under the curve (AUC) was significantly higher than that without CAD support. When the focus was only on panoramic radiographs in which CAD support led to a correct diagnosis, the AUC of the inexperienced dentists increased to an equivalent level to that of the experienced radiologists. CONCLUSIONS: The CAD system supported the inexperienced dentists in diagnosing maxillary sinusitis on the panoramic radiographs. If the accuracy of the CAD system can be increased, the benefits of CAD support will be further enhanced. PMID- 26837672 TI - Developing a multi-Kinect-system for monitoring in dairy cows: object recognition and surface analysis using wavelets. AB - Camera-based systems in dairy cattle were intensively studied over the last years. Different from this study, single camera systems with a limited range of applications were presented, mostly using 2D cameras. This study presents current steps in the development of a camera system comprising multiple 3D cameras (six Microsoft Kinect cameras) for monitoring purposes in dairy cows. An early prototype was constructed, and alpha versions of software for recording, synchronizing, sorting and segmenting images and transforming the 3D data in a joint coordinate system have already been implemented. This study introduced the application of two-dimensional wavelet transforms as method for object recognition and surface analyses. The method was explained in detail, and four differently shaped wavelets were tested with respect to their reconstruction error concerning Kinect recorded depth maps from different camera positions. The images' high frequency parts reconstructed from wavelet decompositions using the haar and the biorthogonal 1.5 wavelet were statistically analyzed with regard to the effects of image fore- or background and of cows' or persons' surface. Furthermore, binary classifiers based on the local high frequencies have been implemented to decide whether a pixel belongs to the image foreground and if it was located on a cow or a person. Classifiers distinguishing between image regions showed high (?0.8) values of Area Under reciever operation characteristic Curve (AUC). The classifications due to species showed maximal AUC values of 0.69. PMID- 26837671 TI - Comparison of a 32-channel head coil and a 2-channel surface coil for MR imaging of the temporomandibular joint at 3.0 T. AB - OBJECTIVE: To quantitatively and qualitatively compare MRI of the temporomandibular joint (TMJ) using a standard TMJ surface coil and a head coil at 3.0 T. METHODS: 22 asymptomatic volunteers were MR imaged using a 2-channel surface coil (standard TMJ coil) and a 32-channel head coil at 3.0 T (Philips Ingenia; Philips Healthcare, Netherlands). Imaging protocol consisted of an oblique sagittal proton density weighted turbo spin echo sequence (repetition time/echo time, 2700/26 ms). For quantitative assessment, a spherical phantom was imaged using the same sequence including a noise scan and a B1+ scan. Signal-to noise ratio (SNR) maps and B1+ maps were calculated on a voxelwise basis. For qualitative evaluation, all volunteers underwent MRI of both TMJs with the jaw in the closed position. Two independent blinded readers assessed accuracy of TMJ anatomical representation and overall image quality on a 5-point scale. Quantitative and qualitative measurements were compared between coils using t tests and Wilcoxon signed-rank test, respectively. RESULTS: Quantitative analysis showed similar B1+ and significantly higher SNR for the head coil than the TMJ surface coil. Qualitative analysis showed significantly better visibility and delineation of clinically relevant anatomical structures of the TMJ, including the articular disc, bilaminar zone and lateral pterygoid muscle. Furthermore, better overall image quality was observed for the head coil than for the TMJ surface coil. CONCLUSIONS: A 32-channel head coil is preferable to a standard 2 channel TMJ surface coil when imaging the TMJ at 3.0 T, because it yields higher SNR, thus increasing accuracy of the anatomical representation of the TMJ. PMID- 26837673 TI - Genetics and Epigenetics of Chronic Allograft Dysfunction in Kidney Transplants. AB - Chronic allograft dysfunction is the most common cause of allograft lost. Chronic allograft dysfunction happens as a result of complex interactions at the molecular and cellular levels. Genetic and environmental factors both influence the evolution and progression of the chronic allograft dysfunction. Epigenetic modification could be considered as a therapeutically modifiable element to pause the fibrosis process through novel strategies. In this review, the PubMed database was searched for English-language articles on these new areas. PMID- 26837674 TI - Acute Renal Occlusion as an Unusual Cause of Acute Abdomen. PMID- 26837675 TI - Serum Troponin I Level for Diagnosis of Acute Coronary Syndrome in Patients with Chronic Kidney Disease. AB - INTRODUCTION: Myocardial infarction is a common cause of mortality in patients with chronic kidney disease (CKD). Since troponins I and T levels rise in CKD patients without any myocardial cause, diagnostic value of cardiac troponins is not high in these patients. This study aimed to evaluate the value of troponin I and other cardiac biomarkers to differentiate acute coronary syndrome in CKD patients. MATERIALS AND METHODS: In this cross-sectional study, patients with stage 3 to 5 of CKD with typical chest pain were enrolled. Troponins I and T and other biomarkers were measured, and angiography was carried out in these patients. Cardiac biomarkers and other variables were evaluated in patients and compared with angiography results. RESULTS: Ninety CKD patients with a mean age of 61.67 +/- 15.87 years were enrolled. Angiography results were normal in 48.9% of the patients, while it showed single-vessel disease in 14.5%, two-vessel disease in 23.3%, and three-vessel disease in 13.3%. Serum creatinine level, glomerular filtration rate, troponin I level, and creatine kinase level were not significantly different in patients with normal and abnormal angiography findings. The serum troponin I, creatine kinase, and creatine kinase-myocardial bound levels had no significant diagnostic values to differentiate abnormal angiography in CKD patients. CONCLUSIONS: Serum levels of cardiac troponin I and creatine kinase-myocardial bound were not suitable to diagnose ACS in CKD patients (stages 3 to 5); therefore, we suggest using other diagnostic attempts in similar conditions. More evaluation is needed to confirm these findings. PMID- 26837676 TI - Validation of Oxford Classification of Immunoglobulin A Nephropathy: an Iranian Experience. AB - INTRODUCTION: In 2009, the Oxford classification of immunoglobulin A (IgA) nephropathy was proposed by the working group of the International IgA Nephropathy Network and Renal Pathology Society. It established specific pathologic features that predict the risk of progression of disease. This study aimed to evaluate the interobserver reproducibility of the Oxford classification of IgA nephropathy between Iranian nephropathologists. MATERIALS AND METHODS: We included 100 patients with primary IgA nephropathy diagnosed between 2001 and 2011. Histologic slides were circulated among 4 pathologists. A score sheet was answered by each individual pathologist for each biopsy, according to the instruction of the Oxford classification. Reproducibility was determined for each variable, using intraclass correlation coefficient (ICC). RESULTS: The ICC values calculated for each major category of the Oxford classification were as follows: the highest score of 0.94 for tubular atrophy and interstitial fibrosis; 0.8 for glomerular basement membrane duplication, extracapillary proliferation, and segmental endocapillary proliferation; and 0.1 to 0.3 for arterial lesions, especially for hyalinosis of arterioles and intimal thickening of arcuate vessels and interlobar arteries. CONCLUSIONS: The Oxford classification of IgA nephropathy is a useful tool and evidenced-based method with high interobserver reproducibility in pathology reporting. Our data suggest that Oxford classification may be used as a model for classification of other renal pathologies in the future. PMID- 26837677 TI - Correlation Between Aortic Root Elastic Properties and Glomerular Filtration Rate in Patients With Chronic Kidney Disease. AB - INTRODUCTION: Aortic root stiffness is a highly prevalent condition in patients with chronic kidney disease (CKD), which independently associates with increased risk of mortality and morbidity in this group. This study aimed to investigate the relationship between glomerular filtration rate (GFR) level as a marker of kidney function and elastic properties of aortic root obtained with echocardiography. METHODS AND MATERIALS: Eighty-two patients (53 men and 29 women; mean age, 57.9 +/- 15.0 years) with CKD stages 3 and 4 were enrolled in this study. Echocardiography and tissue Doppler imaging of the upper and lower aortic walls were done. Systolic wave (S wave) was obtained from each walls. Aortic distensibility and aortic root stiffness index were calculated using blood pressure measurement and aortic dimensions in systole and diastole by M-mode echocardiography. RESULTS: In all of the patients, aortic stiffness index (14.24 +/- 9.82), aortic distensibility (0.018 +/- 0.015), aortic upper wall S velocity (0.10 +/- 0.03), and aortic lower wall S velocity (0.08 +/- 0.02) were severely impaired. There was no correlation between GFR and aortic distensibility (r = 0.253, P = .20), aortic root stiffness index (r = 0.193, P = .09), aortic upper wall S velocity (r = -0.106, P = .17), and aortic lower wall S velocity (r = 0.150, P = .09). CONCLUSIONS: Aortic stiffness was seen in all patients with kidney failure in stage 3 or 4 of CKD; however, we could not find any direct relationship between GFR and this phenomenon. Thus, aortic root stiffness may be a consequence of hypertension and other risk factors. PMID- 26837678 TI - Serum Mannose-binding Lectin in Patients on Peritoneal Dialysis Compared With Healthy Individuals. AB - INTRODUCTION: The increased susceptibility to infection in patients with end stage renal disease is probably secondary to the impaired immune defense in uremia. Mannose-binding lectin (MBL) has an important role in host defense through activation of the lectin complement pathway. The aim of this study was to measure serum MBL level in peritoneal dialysis patients and compare it with a healthy group. MATERIALS AND METHODS: Seventy peritoneal dialysis patients and 70 healthy individuals were enrolled in this study. Serum MBL levels were measured by an enzyme-linked immunosorbent assay kit using the mannan molecule. In addition, serum C-reactive protein and albumin levels were measured to determine whether there is a correlation between serum MBL level and these two parameters. RESULTS: The mean serum MBL level was 2.32 +/- 2.54 ug/mL (range, zero to 6.93 ug/mL) in the patients group and 1.80 +/- 2.14 ug/mL (range, zero to 6.97ug/mL) in the control group (P = .19). No significant correlation was detected between age and serum MBL level in either the groups. In the patients group, no significant correlation was found between serum MBL and C-reactive protein levels or MBL and albumin levels. There were no correlation between duration of peritoneal dialysis and MBL or dialysis adequacy and MBL, either. CONCLUSIONS: This study did not find MBL deficiency in peritoneal dialysis patients as compared to the healthy individuals. PMID- 26837679 TI - Association of Handgrip Strength With Malnutrition-Inflammation Score as an Assessment of Nutritional Status in Hemodialysis Patients. AB - INTRODUCTION: Protein-energy wasting (PEW) is very common in patients with chronic kidney disease and those undergoing maintenance dialysis. Reduced handgrip strength is associated with PEW and considered as a reliable nutritional parameter that reflects loss of muscle mass. This study aimed to evaluate the handgrip strength and its relationship with the Malnutrition-Inflammation Score (MIS) among Iranian dialysis patients. MATERIALS AND METHODS: The study population consisted of 83 randomly selected hemodialysis patients from the dialysis centers in Kerman, Iran. Handgrip strength was measured using a dynamometer according to the recommendations of the American Society of Hand Therapists. All the patients were interviewed and the MIS of the patients were recorded. Results. The PEW was prevalent in Kerman hemodialysis patients, with 83% and 17% having mild and moderate PEW based on MIS, respectively. Handgrip strength was significantly associated with age, sex, height, weight, and diabetes mellitus. After adjustment for age, handgrip strength was significantly associated with nutritional assessment markers on the basis of the MIS. CONCLUSIONS: Handgrip strength can be incorporated as a reliable tool for assessing nutrition status in clinical practice. However, further research is needed to determine the reference values and cutoff points both in healthy people and in hemodialysis patients to classify muscle wasting. PMID- 26837680 TI - Absolute and Relative Carnitine Deficiency in Patients on Hemodialysis and Peritoneal Dialysis. AB - INTRODUCTION: Carnitine deficiency is commonly seen in dialysis patients. This study assessed the association dialysis and pediatric patients' characteristics with plasma carnitines levels. MATERIALS AND METHODS: Plasma carnitine concentrations were measured by tandem mass spectrometry in 46 children on hemodialysis or peritoneal dialysis. The total carnitine, free carnitine (FC), and L-acyl carnitine (AC) levels of 40 umol/L and less, less than 7 umol/L, and less than 15 umol/L were defined low, respectively. An FC less than 20 umol/L and an AC/FC ratio greater than 0.4 were considered as absolute and relative carnitine deficiencies. The correlation between carnitines levels and AC/FC ratio and age, duration of dialysis, characteristics of dialysis, and blood urea nitrogen and serum albumin concentrations were assessed. RESULTS: Absolute carnitine deficiency, low total carnitine, and low AC concentrations were found in 66.7%, 82.6%, and 51% of the patients, respectively. All of the patients had relative carnitine deficiency. Carnitine measurements were not significantly different between the hemodialysis and peritoneal dialysis groups. More severe relative carnitine deficiency was found in those with lower blood urea nitrogen levels and those on peritoneal dialysis. No linear correlation was found between carnitine levels and age, duration of dialysis, characteristics of dialysis, serum albumin level, or blood urea nitrogen level. CONCLUSIONS: Absolute and relative carnitine deficiencies are common among children on dialysis. Patients with lower blood urea nitrogen levels and peritoneal dialysis patients are more prone to severe relative carnitine deficiency. PMID- 26837681 TI - A Novel Mutation in SLC3A1 Gene in Patients With Cystinuria. AB - Cystinuria is an inherited disease characterized by the formation of cystine calculi in the kidneys, ureters, and bladder. Cystinuria is associated with mutation in the SLC3A1 and SLC7A9 genes. These defects prevent appropriate reabsorption of dibasic amino acids lysine, ornithine, and arginine. Cystinuria is classified as type I (silent heterozygotes) and non-type I (heterozygotes with urinary hyperexcretion of cystine). In molecular term, cystinuria is classified as type A (mutations on SLC3A1 gene) and type B (mutations on SLC7A9 gene). This report describes 7 patients with early onset of cystine calculus formation. We are report a new mutation in SLC3A1 gene in exon 1. A novel nucleotide substitution c.-29A>G was found in exon 1 of the SLC3A1 gene, which had not been reported elsewhere previously. PMID- 26837682 TI - Coexistence of Fabry Disease and Membranous Nephropathy. AB - A 21-year-old man with no family history or characteristic symptoms of Fabry disease presented with proteinuria. Histological and immunofluorescent analysis of kidney tissue collected revealed stage 1 membranous nephropathy. Electron microscopy of the same tissue revealed a large number of myeloid bodies (zebra bodies) in the glomerular epithelial cytoplasm and a mild irregular thickening of basement membrane. A diagnosis of Fabry disease was supported by the low alpha galactosidase A activity detected in the patient's plasma, and confirmed by the detection of a pathogenic homozygous mutation in the alpha-galactosidase A gene. Therefore, the final diagnosis was of coexistent Fabry disease and stage 1 membranous nephropathy. This is the first case study reporting the coexistence of Fabry disease and membranous nephropathy. Our results emphasize the importance of electron microscopy in Fabry disease diagnosis. PMID- 26837683 TI - Improving the user experience of patient versions of clinical guidelines: user testing of a Scottish Intercollegiate Guideline Network (SIGN) patient version. AB - BACKGROUND: Guideline producers are increasingly producing versions of guidelines for the public, and knowledge of what the public want from them is also increasing. The aim of this study was to user test a patient version of a SIGN clinical guideline that was designed based on preliminary work for the DECIDE project. SIGN is the leading national guideline producer in Scotland. METHODS: People with a diagnosis of glaucoma and non-professional carers were recruited from across Scotland. User testing was conducted using a think-aloud protocol method. Each session was conducted by one interviewer and one observer. All sessions were recorded and transcribed. The data was analysed, problems with the guideline were identified and resolved and key findings were themed using a user experience model. RESULTS: Thirteen user testing sessions with people with glaucoma and one with a carer were conducted. Key facilitators of desirability and usability identified include clear branding as a patient version and a clearly described purpose, audience and contents page. Other facilitators include a "friendly" tone which is achieved by the use of colour, quotes, icons, simple language and charts, and brief chunked text. The value and usefulness of the patient guideline was influenced by its ability to: inform the public, link information to actions, and empower people in their interaction with healthcare professionals. Participants were disappointed by the lack of information on treatment in the patient version, which was outside its scope. Information on the evidence based guideline production process and the involvement of appropriately skilled professionals was key to the credibility of the guideline. Lack of awareness of guidelines and guideline producing bodies, is a potentially serious threat to findability/accessibility. CONCLUSIONS: It is important for guideline producers to maximise the user experience of the public when they access patient versions of guidelines, particularly given the current low level of access and awareness. One size does not fit all and guideline producers need to strike a balance between keeping the patient version simple and providing sufficient information to facilitate shared decision making and empower the public. Guideline producers may find the results of this study useful in designing their own patient versions. PMID- 26837685 TI - Associations of depression status and hopelessness with breast cancer: A 24-year follow-up study. AB - This study extended the literature by examining whether three profiles of depression predicted breast cancer status. In 1076 women of the Baltimore Epidemiologic Catchment Area study, depression status and hopelessness were measured at baseline and breast cancer status was ascertained 24 years later. Double depression, but not major depression or dysthymia, was associated with breast cancer. Hopelessness predicted fewer new cases of breast cancer. When double depression and hopelessness were simultaneously entered as predictors, the regression weights of both predictors increased. The role of severe and extended duration depression as well as possible explanations for unexpected findings are discussed. PMID- 26837684 TI - Therapist guided internet based cognitive behavioural therapy for body dysmorphic disorder: single blind randomised controlled trial. AB - OBJECTIVES: To evaluate the efficacy of therapist guided internet based cognitive behavioural therapy (CBT) programme for body dysmorphic disorder (BDD-NET) compared with online supportive therapy. DESIGN: A 12 week single blind parallel group randomised controlled trial. SETTING: Academic medical centre. PARTICIPANTS: 94 self referred adult outpatients with a diagnosis of body dysmorphic disorder and a modified Yale-Brown obsessive compulsive scale (BDD YBOCS) score of >= 20. Concurrent psychotropic drug treatment was permitted if the dose had been stable for at least two months before enrolment and remained unchanged during the trial. INTERVENTIONS: Participants received either BDD-NET (n=47) or supportive therapy (n=47) delivered via the internet for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome was the BDD-YBOCS score after treatment and follow-up (three and six months from baseline) as evaluated by a masked assessor. Responder status was defined as a >= 30% reduction in symptoms on the scale. Secondary outcomes were measures of depression (MADRS-S), global functioning (GAF), clinical global improvement (CGI-I), and quality of life (EQ5D). The six month follow-up time and all outcomes other than BDD-YBOCS and MADRS-S at 3 months were not pre-specified in the registration at clinicaltrials.gov because of an administrative error but were included in the original trial protocol approved by the regional ethics committee before the start of the trial. RESULTS: BDD-NET was superior to supportive therapy and was associated with significant improvements in severity of symptoms of body dysmorphic disorder (BDD-YBOCS group difference -7.1 points, 95% confidence interval -9.8 to -4.4), depression (MADRS S group difference -4.5 points, -7.5 to -1.4), and other secondary measures. At follow-up, 56% of those receiving BDD-NET were classed as responders, compared with 13% receiving supportive therapy. The number needed to treat was 2.34 (1.71 to 4.35). Self reported satisfaction was high. CONCLUSIONS: CBT can be delivered safely via the internet to patients with body dysmorphic disorder. BDD-NET has the potential to increase access to evidence based psychiatric care for this mental disorder, in line with NICE priority recommendations. It could be particularly useful in a stepped care approach, in which general practitioner or other mental health professionals can offer treatment to people with mild to moderate symptoms at low risk of suicide.Trial registration ClinicalTrials.gov ID: NCT02010619. PMID- 26837686 TI - Public perceptions of personalised nutrition through the lens of Social Cognitive Theory. AB - Social Cognitive Theory has been used to explain findings derived from focus group discussions ( N = 4) held in the United Kingdom with the aim of informing best practice in personalised nutrition. Positive expectancies included weight loss and negative expectancies surrounded on-line security. Monitoring and feedback were crucial to goal setting and progress. Coaching by the service provider, family and friends was deemed important for self-efficacy. Paying for personalised nutrition symbolised commitment to behaviour change. The social context of eating, however, was perceived a problem and should be considered when designing personalised diets. Social Cognitive Theory could provide an effective framework through which to deliver personalised nutrition. PMID- 26837687 TI - The relation of trait and state mindfulness with satisfaction and physical activity: A cross-sectional study in 305 Dutch participants. AB - Previous research has shown that satisfaction mediates the relationship of state mindfulness (i.e. during physical activity) with physical activity. This study aimed to replicate this finding and to explore the role of trait mindfulness with a cross-sectional design. In all, 305 participants completed measures on trait and state mindfulness, satisfaction with physical activity, and physical activity. Mediation analyses were used. Satisfaction mediated the effect of state mindfulness on physical activity. Trait mindfulness related to physical activity via an indirect path, namely through two consecutive mediators, first state mindfulness and then satisfaction. Our results suggest that to enhance satisfaction, both state and trait mindfulness should be considered. PMID- 26837688 TI - Type D personality and physical inactivity: The mediating effects of low self efficacy. AB - Type D personality is associated with health-damaging behaviours among the general population. This study assessed the relationship between Type D personality, physical activity and self-efficacy. A total of 189 participants completed measures of Type D personality, physical activity and self-efficacy. Type D individuals had significantly lower levels of self-efficacy and engaged in significantly less walking and total exercise compared to non-Type D's. Furthermore, self-efficacy fully mediated the relationship between Type D and physical activity. Low levels of self-efficacy may be one mechanism to help explain why Type D individuals engage in more disease-promoting behaviours. PMID- 26837689 TI - 'I was in control of it from the start': A qualitative study of men's experiences of positive adjustment following a heart attack. AB - A qualitative design was used to explore the experience of positive adjustment following a heart attack. Ten men attending a cardiac rehabilitation programme completed in-depth semi-structured interviews. An overarching theme: 'I was in control of it from the start' emerged with six subthemes, relating to intrapersonal and interpersonal factors and processes. The subthemes reflected the importance of identifying controllable versus non-controllable factors and employing adaptive coping strategies. PMID- 26837690 TI - People living with facial disfigurement after having had noma disease: A systematic review of the literature. AB - Noma disease often results in impairment, morbidity and severe facial disfigurement. This article reports a systematic review of literatures published between 2006 and 2015 to establish existing knowledge about social stigma associated with facial disfigurements. Five databases were searched and 114 citations were screened, of which only 15 met the relevant criteria. Titles and abstracts of the retrieved articles were independently reviewed. The research was heterogeneous; therefore, overall synthesis using meta-analysis was inappropriate. It can be seen that the review demonstrates that facial disfigurements are far more complex than was previously thought. PMID- 26837691 TI - Acute spinal cord injury patients' satisfaction with care: Results from an intervention study in a specialized rehabilitation unit. AB - To assess satisfaction with care in acute spinal cord injury patients admitted to a specialized rehabilitation unit prior and after a tailored training in communication skills for the staff, the Picker Patient Experience-33 ((1) Content of the information, (2) Quality of the information, and (3) Quality of the relationship), the Spinal Cord Independence Measure-III, and the Hospital Anxiety and Depression Scale were administered. The more troublesome dimension regarding patients' satisfaction was content of the information, with 88.37 and 91.43 percent (pre/post-intervention) reporting problems with information provided concerning their rights, and 51.15 and 58.72 percent (pre/post-intervention) with the information received at discharge. Overall, functionality (Spinal Cord Independence Measure-III) improved at discharge, but Hospital Anxiety and Depression Scale pre/post-scores revealed to be high. PMID- 26837692 TI - Oncology healthcare professionals' perspectives on the psychosocial support needs of cancer patients during oncology treatment. AB - This study explored oncology healthcare professionals' perspectives on the psychosocial support needs of diverse cancer patients during oncology treatment. Six themes were identified using thematic analysis. Healthcare professionals highlighted the importance of their sensitivity, respect and emotional tact during appointments in order to effectively identify and meet the needs of oncology patients. Participants also emphasised the importance of building rapport that recognises patients as people. Patients' acceptance of treatment related distress and uncertainty was described as required for uptake of available psychosocial supportive services. We offer some practical implications that may help improve cancer patients' experiences during oncology treatment. PMID- 26837693 TI - Clear cell carcinomas of the ovary: a mono-institutional study of 73 cases in China with an analysis of the prognostic significance of clinicopathological parameters and IMP3 expression. AB - BACKGROUND: Ovarian clear cell carcinoma (CCC) is an uncommon subtype of ovarian epithelial tumor. The prognostic significance of its clinicopathological parameters is discordant, with the exception of stage as the adverse prognostic factor. The present study aimed to evaluate the prognostic significance of its clinicopathological characteristics and the expression of IMP3 (Insulin-like growth factor-II mRNA-binding protein 3, IMP3 or IGF2BP3) in Chinese patients with primary pure CCC. METHODS: We collected clinicopathological data from 73 cases with a minimum of 5 years of follow-up and evaluated the expression of IMP3 by immunohistochemistry. RESULTS: In total, 49.3 % of the patients were in stage I. Advanced stages were closely related to poor prognosis of disease-free survival (DFS) and overall survival (OS) (P < 0.005). Patients with CCC coexisting with endometriosis tended to be younger and to have unilateral involvement but did not exhibit differences in prognosis compared with patients with CCC without endometriosis. Other histological features such as growth pattern, mitosis, and necrosis did not have prognostic significance. IMP3 was positive in 63 % of patients (46 of 73 cases); Thus, positive expression of IMP3 is an adverse prognostic marker in terms of OS (P = 0.012), even in stage I patients (P = 0.038). CONCLUSIONS: The present study demonstrates that IMP3 expression is a prognostic marker, with the exception of stage. IMP3 represents a biomarker of unfavorable prognosis even in stage I patients. PMID- 26837694 TI - Pulmonary metastasectomy in pediatric patients. AB - BACKGROUND: This study aims to evaluate the outcomes of pulmonary metastasectomy resections in pediatric patients. METHODS: We retrospectively reviewed the medical records of 43 children who were operated on in the Pediatric Surgery Clinic between January 1988 and 2014. Forty-three children (26 boys; 17 girls; mean age 10+/-4.24 years, range 6 months-18 years) who underwent pulmonary metastasectomy resection were included in the study. The patients were evaluated based on age, gender, history of disease, surgical procedures, complications, duration of hospitalization, duration of chest tube placement, and procedure outcome. RESULTS: Indications for pediatric resections were oncological. Metastasis was secondary to Wilms' tumor in 14 patients, osteosarcoma in 7 patients, Ewing's sarcoma in 5 patients, rhabdomyosarcoma in 5 patients, lymphoma in 3 patients, hepatoblastoma in 2 patients, and other tumors in 7 patients. A total of 59 thoracotomies were performed. Approaches utilized included unilateral posterolateral thoracotomy (n=33), bilateral posterolateral thoracotomy (n=8), and sternotomy (n=2). Wedge resection was the procedure of choice (n=44). In selected cases, 11 segmentectomies, 3 lobectomies, and 1 pneumonectomy were performed. There was no perioperative mortality. One patient suffered prolonged air leak and three patients from fever. All patients received chemotherapy. Radiotherapy was administered to 16 patients (37.2%). Of those 16 patients, 7 had Wilms' tumor, 6 had Ewing's sarcoma/PNET, and 3 were rhabdomyosarcoma patients. During a median follow-up of 3 years, the overall survival was 74.4%. CONCLUSIONS: Multidisciplinary treatment involving pediatric oncologists, surgeons, and radiation oncologists is necessary to obtain positive results in children who have pulmonary metastases of oncological diseases. Wedge resection is a suitable option for children because less lung tissue is resected. PMID- 26837697 TI - A meta-analysis of low-molecular-weight heparin to prevent pregnancy loss in women with inherited thrombophilia. AB - We performed a meta-analysis of randomized controlled trials comparing low molecular-weight heparin (LMWH) vs no LMWH in women with inherited thrombophilia and prior late (>=10 weeks) or recurrent early (<10 weeks) pregnancy loss. Eight trials and 483 patients met our inclusion criteria. There was no significant difference in livebirth rates with the use of LMWH compared with no LMWH (relative risk, 0.81; 95% confidence interval, 0.55-1.19;P= .28), suggesting no benefit of LMWH in preventing recurrent pregnancy loss in women with inherited thrombophilia. PMID- 26837698 TI - Large B-cell transformation in nodular lymphocyte-predominant Hodgkin lymphoma: 40-year experience from a single institution. AB - A number of reports have shown a propensity of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) to transform into diffuse large B-cell lymphoma (DLBCL). Long-term data on the incidence and outcomes of transformed NLPHL are lacking. A comprehensive analysis of the actively maintained Mayo Clinic Lymphoma Database was performed. Between 1970 and 2011, 222 consecutive adult patients with new untreated NLPHL were identified. Median age at diagnosis was 40 years, and 146 (66%) were males. The median follow-up was 16 years. Seventeen patients (7.6%) developed a transformation to DLBCL. The median time to transformation was 35 months (range, 6-268 months). Based on the observed 17 transformations during 2304 patient-years of follow-up, the rate of transformation was 0.74 per 100 patient-years. In a multivariate analysis, use of any prior chemotherapy ( ITALIC! P= .04) and splenic involvement ( ITALIC! P= .03) were significantly associated with increased risk of transformation. The 5-year overall survival (OS) in those with transformed disease was 76.4%, and transformation did not adversely affect OS when compared with patients who did not experience transformation. In this large single-institution cohort with long-term follow-up, the risk of transformation was lower than that observed in other low-grade lymphomas. PMID- 26837702 TI - Oxidative Addition of CH3I to Au(-) in the Gas Phase. AB - Reaction of the atomic gold anion (Au(-)) with CH3I under high-pressure helium gas affords the adduct AuCH3I(-). Photoelectron spectroscopy and density functional theory calculations reveal that in the AuCH3I(-) structure the I and CH3 fragments of CH3I are bonded to Au in a linear configuration, which can be viewed as an oxidative addition product. Theoretical studies indicate that oxidative addition proceeds in two steps: nucleophilic attack of Au(-) on CH3I, followed by migration of the leaving I(-) to Au. This mechanism is supported by the formation of an ion-neutral complex, [Au(-)...t-C4H9I], in the reaction of Au(-) with t-C4H9I because of the activation barrier along the SN2 pathway resulting from steric effects. Theoretical studies are conducted for the formation mechanism of AuI2(-), which is observed as a major product. From the thermodynamic and kinetic viewpoints, we propose that AuI2(-) is formed via sequential oxidative addition of two CH3I molecules to Au(-), followed by reductive elimination of C2H6. The results suggest that Au(-) acts as a nucleophile to activate C(sp(3))-I bond of CH3I and induces the C-C coupling reaction of CH3I. PMID- 26837699 TI - Clinical impact of clonal and subclonal TP53, SF3B1, BIRC3, NOTCH1, and ATM mutations in chronic lymphocytic leukemia. AB - Genomic studies have revealed the complex clonal heterogeneity of chronic lymphocytic leukemia (CLL). The acquisition and selection of genomic aberrations may be critical to understanding the progression of this disease. In this study, we have extensively characterized the mutational status of TP53, SF3B1, BIRC3, NOTCH1, and ATM in 406 untreated CLL cases by ultra-deep next-generation sequencing, which detected subclonal mutations down to 0.3% allele frequency. Clonal dynamics were examined in longitudinal samples of 48 CLL patients. We identified a high proportion of subclonal mutations, isolated or associated with clonal aberrations. TP53 mutations were present in 10.6% of patients (6.4% clonal, 4.2% subclonal), ATM mutations in 11.1% (7.8% clonal, 1.3% subclonal, 2% germ line mutations considered pathogenic), SF3B1 mutations in 12.6% (7.4% clonal, 5.2% subclonal), NOTCH1 mutations in 21.8% (14.2% clonal, 7.6% subclonal), and BIRC3 mutations in 4.2% (2% clonal, 2.2% subclonal). ATM mutations, clonal SF3B1, and both clonal and subclonal NOTCH1 mutations predicted for shorter time to first treatment irrespective of the immunoglobulin heavy chain variable-region gene (IGHV) mutational status. Clonal and subclonal TP53 and clonal NOTCH1 mutations predicted for shorter overall survival together with the IGHV mutational status. Clonal evolution in longitudinal samples mainly occurred in cases with mutations in the initial samples and was observed not only after chemotherapy but also in untreated patients. These findings suggest that the characterization of the subclonal architecture and its dynamics in the evolution of the disease may be relevant for the management of CLL patients. PMID- 26837701 TI - Consensus statement from the International Radiosurgery Oncology Consortium for Kidney for primary renal cell carcinoma. AB - AIM: To provide a multi-institutional consensus document for stereotactic body radiotherapy of primary renal cell carcinoma. MATERIALS & METHODS: Eight international institutions completed a 65-item survey covering patient selection, planning/treatment aspects and response evaluation. RESULTS: All centers treat patients with pre-existing hypertension and solitary kidneys. Five institutions apply size constraints of 5-8 cm. The total planning target volume expansion is 3 10 mm. All institutions perform pretreatment imaging verification, while seven institutions perform some form of intrafractional monitoring. Number of fractions used are 1-12 to a total dose of 25 Gy-80 GyE. Imaging follow-up for local tumor response includes computed tomography (n = 8), PET-computed tomography (n = 1) and MRI (n = 5). Follow-up frequency is 3-6 months for the first 2 years and 3-12 months for subsequent 3 years. CONCLUSION: Key methods for safe implementation and practice for stereotactic body radiotherapy kidney have been identified and may aid standardization of treatment delivery. PMID- 26837700 TI - Caveolin-1 regulates TCR signal strength and regulatory T-cell differentiation into alloreactive T cells. AB - Caveolin-1 (Cav-1) is a key organizer of membrane specializations and a scaffold protein that regulates signaling in multiple cell types. We found increased Cav-1 expression in human and murine T cells after allogeneic hematopoietic cell transplantation. Indeed, Cav-1(-/-)donor T cells caused less severe acute graft versus-host disease (GVHD) and yielded higher numbers of regulatory T cells (Tregs) compared with controls. Depletion of Tregs from the graft abrogated this protective effect. Correspondingly, Treg frequencies increased when Cav-1(-/-)T cells were exposed to transforming growth factor-beta/T-cell receptor (TCR)/CD28 activation or alloantigen stimulation in vitro compared with wild-type T cells. Mechanistically, we found that the phosphorylation of Cav-1 is dispensable for the control of T-cell fate by using a nonphosphorylatable Cav-1 (Y14F/Y14F) point mutation variant. Moreover, the close proximity of lymphocyte-specific protein tyrosine kinase (Lck) to the TCR induced by TCR-activation was reduced in Cav-1( /-)T cells. Therefore, less TCR/Lck clustering results in suboptimal activation of the downstream signaling events, which correlates with the preferential development into a Treg phenotype. Overall, we report a novel role for Cav-1 in TCR/Lck spatial distribution upon TCR triggering, which controls T-cell fate toward a regulatory phenotype. This alteration translated into a significant increase in the frequency of Tregs and reduced GVHD in vivo. PMID- 26837703 TI - Ozone-Induced Hypertussive Responses in Rabbits and Guinea Pigs. AB - Cough remains a major unmet clinical need, and preclinical animal models are not predictive for new antitussive agents. We have investigated the mechanisms and pharmacological sensitivity of ozone-induced hypertussive responses in rabbits and guinea pigs. Ozone induced a significant increase in cough frequency and a decrease in time to first cough to inhaled citric acid in both conscious guinea pigs and rabbits. This response was inhibited by the established antitussive drugs codeine and levodropropizine. In contrast to the guinea pig, hypertussive responses in the rabbit were not inhibited by bronchodilator drugs (beta2 agonists or muscarinic receptor antagonists), suggesting that the observed hypertussive state was not secondary to bronchoconstriction in this species. The ozone-induced hypertussive response in the rabbit was inhibited by chronic pretreatment with capsaicin, suggestive of a sensitization of airway sensory nerve fibers. However, we could find no evidence for a role of TRPA1 in this response, suggesting that ozone was not sensitizing airway sensory nerves via activation of this receptor. Whereas the ozone-induced hypertussive response was accompanied by a significant influx of neutrophils into the airway, the hypertussive response was not inhibited by the anti-inflammatory phosphodiesterase 4 inhibitor roflumilast at a dose that clearly exhibited anti inflammatory activity. In summary, our results suggest that ozone-induced hypertussive responses to citric acid may provide a useful model for the investigation of novel drugs for the treatment of cough, but some important differences were noted between the two species with respect to sensitivity to bronchodilator drugs. PMID- 26837704 TI - Omics for prediction of environmental health effects: Blood leukocyte-based cross omic profiling reliably predicts diseases associated with tobacco smoking. AB - The utility of blood-based omic profiles for linking environmental exposures to their potential health effects was evaluated in 649 individuals, drawn from the general population, in relation to tobacco smoking, an exposure with well characterised health effects. Using disease connectivity analysis, we found that the combination of smoking-modified, genome-wide gene (including miRNA) expression and DNA methylation profiles predicts with remarkable reliability most diseases and conditions independently known to be causally associated with smoking (indicative estimates of sensitivity and positive predictive value 94% and 84%, respectively). Bioinformatics analysis reveals the importance of a small number of smoking-modified, master-regulatory genes and suggest a central role for altered ubiquitination. The smoking-induced gene expression profiles overlap significantly with profiles present in blood cells of patients with lung cancer or coronary heart disease, diseases strongly associated with tobacco smoking. These results provide proof-of-principle support to the suggestion that omic profiling in peripheral blood has the potential of identifying early, disease related perturbations caused by toxic exposures and may be a useful tool in hazard and risk assessment. PMID- 26837705 TI - Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions. AB - DNA-binding proteins search for specific targets via facilitated diffusion along a crowded genome. However, little is known about how crowded DNA modulates facilitated diffusion and target recognition. Here we use DNA curtains and single molecule fluorescence imaging to investigate how Msh2-Msh3, a eukaryotic mismatch repair complex, navigates on crowded DNA. Msh2-Msh3 hops over nucleosomes and other protein roadblocks, but maintains sufficient contact with DNA to recognize a single lesion. In contrast, Msh2-Msh6 slides without hopping and is largely blocked by protein roadblocks. Remarkably, the Msh3-specific mispair-binding domain (MBD) licences a chimeric Msh2-Msh6(3MBD) to bypass nucleosomes. Our studies contrast how Msh2-Msh3 and Msh2-Msh6 navigate on a crowded genome and suggest how Msh2-Msh3 locates DNA lesions outside of replication-coupled repair. These results also provide insights into how DNA repair factors search for DNA lesions in the context of chromatin. PMID- 26837707 TI - Lignocellulosic ethanol production by starch-base industrial yeast under PEG detoxification. AB - Cellulosic ethanol production from lignocellulosic biomass offers a sustainable solution for transition from fossil based fuels to renewable alternatives. However, a few long-standing technical challenges remain to be addressed in the development of an economically viable fermentation process from lignocellulose. Such challenges include the needs to improve yeast tolerance to toxic inhibitory compounds and to achieve high fermentation efficiency with minimum detoxification steps after a simple biomass pretreatment. Here we report an in-situ detoxification strategy by PEG exo-protection of an industrial dry yeast (starch base). The exo-protected yeast cells displayed remarkably boosted vitality with high tolerance to toxic inhibitory compounds, and with largely improved ethanol productivity from crude hydrolysate derived from a pretreated lignocellulose. The PEG chemical exo-protection makes the industrial S. cerevisiae yeast directly applicable for the production of cellulosic ethanol with substantially improved productivity and yield, without of the need to use genetically modified microorganisms. PMID- 26837706 TI - Transthyretin participates in beta-amyloid transport from the brain to the liver- involvement of the low-density lipoprotein receptor-related protein 1? AB - Transthyretin (TTR) binds Abeta peptide, preventing its deposition and toxicity. TTR is decreased in Alzheimer's disease (AD) patients. Additionally, AD transgenic mice with only one copy of the TTR gene show increased brain and plasma Abeta levels when compared to AD mice with both copies of the gene, suggesting TTR involvement in brain Abeta efflux and/or peripheral clearance. Here we showed that TTR promotes Abeta internalization and efflux in a human cerebral microvascular endothelial cell line, hCMEC/D3. TTR also stimulated brain to-blood but not blood-to-brain Abeta permeability in hCMEC/D3, suggesting that TTR interacts directly with Abeta at the blood-brain-barrier. We also observed that TTR crosses the monolayer of cells only in the brain-to-blood direction, as confirmed by in vivo studies, suggesting that TTR can transport Abeta from, but not into the brain. Furthermore, TTR increased Abeta internalization by SAHep cells and by primary hepatocytes from TTR+/+ mice when compared to TTR-/- animals. We propose that TTR-mediated Abeta clearance is through LRP1, as lower receptor expression was found in brains and livers of TTR-/- mice and in cells incubated without TTR. Our results suggest that TTR acts as a carrier of Abeta at the blood-brain-barrier and liver, using LRP1. PMID- 26837709 TI - Gut microbiota: Host faecal miRNA regulates gut microbiota. PMID- 26837708 TI - An efficient Potato virus X -based microRNA silencing in Nicotiana benthamiana. AB - Plant microRNAs (miRNAs) play pivotal roles in many biological processes. Although many miRNAs have been identified in various plant species, the functions of these miRNAs remain largely unknown due to the shortage of effective genetic tools to block their functional activity. Recently, miRNA target mimic (TM) technologies have been applied to perturb the activity of specific endogenous miRNA or miRNA families. We previously reported that Tobacco rattle virus (TRV) based TM expression can successfully mediate virus-based miRNA silencing/suppression (VbMS) in plants. In this study, we show the Potato virus X (PVX)-based TM expression causes strong miRNA silencing in Nicotiana benthamiana. The PVX-based expression of short tandem target mimic (STTMs) against miR165/166 and 159 caused the corresponding phenotype in all infected plants. Thus, a PVX based VbMS is a powerful method to study miRNA function and may be useful for high-throughput investigation of miRNA function in N. benthamiana. PMID- 26837710 TI - Neurogastroenterology: Enteric neurons and macrophage crosstalk. PMID- 26837711 TI - IBS: Treating IBS with diarrhoea. PMID- 26837712 TI - Acute-on-chronic liver failure: terminology, mechanisms and management. AB - Acute-on-chronic liver failure (ACLF) is a distinct clinical entity and differs from acute liver failure and decompensated cirrhosis in timing, presence of acute precipitant, course of disease and potential for unaided recovery. The definition involves outlining the acute and chronic insults to include a homogenous patient group with liver failure and an expected outcome in a specific timeframe. The pathophysiology of ACLF relates to persistent inflammation, immune dysregulation with initial wide-spread immune activation, a state of systematic inflammatory response syndrome and subsequent sepsis due to immune paresis. The disease severity and outcome can be predicted by both hepatic and extrahepatic organ failure(s). Clinical recovery is expected with the use of nucleoside analogues for hepatitis B, and steroids for severe alcoholic hepatitis and, possibly, severe autoimmune hepatitis. Artificial liver support systems help remove toxins and metabolites and serve as a bridge therapy before liver transplantation. Hepatic regeneration during ongoing liver failure, although challenging, is possible through the use of growth factors. Liver transplantation remains the definitive treatment with a good outcome. Pre-emptive antiviral agents for hepatitis B before chemotherapy to prevent viral reactivation and caution in using potentially hepatotoxic drugs can prevent the development of ACLF. PMID- 26837715 TI - Aberrant cervical vasculature anastomosis as cause of neck pain and successful treatment with embolization technique. AB - We report a patient with non-dermatomal radiating neck pain without focal neurologic deficit. Traditional workup could not identify an anatomic or biomechanical cause. Imaging showed a deep cervical vessel centered in the region of pain. Angiography later identified an aberrant anastomosis of this vessel with the occipital artery. Subsequent endovascular embolization of this arterial trunk resulted in complete pain relief. PMID- 26837714 TI - Epigenetic re-expression of HIF-2alpha suppresses soft tissue sarcoma growth. AB - In soft tissue sarcomas (STS), low intratumoural O2 (hypoxia) is a poor prognostic indicator. HIF-1alpha mediates key transcriptional responses to hypoxia, and promotes STS metastasis; however, the role of the related HIF-2alpha protein is unknown. Surprisingly, here we show that HIF-2alpha inhibits high grade STS cell growth in vivo, as loss of HIF-2alpha promotes sarcoma proliferation and increases calcium and mTORC1 signalling in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. We find that most human STS have lower levels of EPAS1 (the gene encoding HIF-2alpha) expression relative to normal tissue. Many cancers, including STS, contain altered epigenetics, and our findings define an epigenetic mechanism whereby EPAS1 is silenced during sarcoma progression. The clinically approved HDAC inhibitor Vorinostat specifically increases HIF-2alpha, but not HIF-1alpha, accumulation in multiple STS subtypes. Vorinostat inhibits STS tumour growth, an effect ameliorated by HIF-2alpha deletion, implicating HIF-2alpha as a biomarker for Vorinostat efficacy in STS. PMID- 26837713 TI - Plasticity of the brush border - the yin and yang of intestinal homeostasis. AB - The brush border on the apical surface of enterocytes is a highly specialized structure well-adapted for efficient digestion and nutrient transport, whilst at the same time providing a protective barrier for the intestinal mucosa. The brush border is constituted of a densely ordered array of microvilli, protrusions of the plasma membrane, which are supported by actin-based microfilaments and interacting proteins and anchored in an apical network of actomyosin and intermediate filaments, the so-called terminal web. The highly dynamic, specialized apical domain is both an essential partner for the gut microbiota and an efficient signalling platform that enables adaptation to physiological stimuli from the external and internal milieu. Nevertheless, genetic alterations or various pathological stresses, such as infection, inflammation, and mechanical or nutritional alterations, can jeopardize this equilibrium and compromise intestinal functions. Long-time neglected, the intestinal brush-border shall be enlightening again as the central actor of the complex but essential intestinal homeostasis. Here, we review the processes and components involved in brush border organization and discuss pathological mechanisms that can induce brush border defects and their physiological consequences. PMID- 26837717 TI - Early changes in condylar position after mandibular advancement: a three dimensional analysis. AB - The aim of this study was to perform a three-dimensional (3D) assessment of positional changes of the mandibular condyle after bilateral sagittal split osteotomy (BSSO). A prospective evaluation of 22 skeletal class II patients who underwent a BSSO for mandibular advancement was performed. Pre- and postoperative cone beam computed tomography scans were taken. Using the cranial base as a stable reference, the pre- and postoperative 3D skull models were superimposed virtually. Positional changes of the condyles were assessed with a 3D colour mapping system (SimPlant O&O). A Brunner-Langer statistical test was applied to test the null hypothesis that the condylar position remains stable after BSSO. The level of significance was set at 0.05. The mean mandibular advancement in the studied sample was 6.7+/-1.6mm. Overall, the condylar positional changes after BSSO for mandibular advancement were statistically significant (P<0.05). A positive correlation was found between the displacement of the left condyle and the amount of mandibular advancement (P<0.01). The results of this study suggest that statistically significant changes of condylar position occur after mandibular advancement. Long-term evaluation is needed to assess the capacity of the temporomandibular joint to adapt to these changes. PMID- 26837716 TI - Organization of descending neurons in Drosophila melanogaster. AB - Neural processing in the brain controls behavior through descending neurons (DNs) - neurons which carry signals from the brain to the spinal cord (or thoracic ganglia in insects). Because DNs arise from multiple circuits in the brain, the numerical simplicity and availability of genetic tools make Drosophila a tractable model for understanding descending motor control. As a first step towards a comprehensive study of descending motor control, here we estimate the number and distribution of DNs in the Drosophila brain. We labeled DNs by backfilling them with dextran dye applied to the neck connective and estimated that there are ~1100 DNs distributed in 6 clusters in Drosophila. To assess the distribution of DNs by neurotransmitters, we labeled DNs in flies in which neurons expressing the major neurotransmitters were also labeled. We found DNs belonging to every neurotransmitter class we tested: acetylcholine, GABA, glutamate, serotonin, dopamine and octopamine. Both the major excitatory neurotransmitter (acetylcholine) and the major inhibitory neurotransmitter (GABA) are employed equally; this stands in contrast to vertebrate DNs which are predominantly excitatory. By comparing the distribution of DNs in Drosophila to those reported previously in other insects, we conclude that the organization of DNs in insects is highly conserved. PMID- 26837718 TI - Implant survival and complications in cases of inferior alveolar nerve lateralization and atrophied mandibles with 5-year follow-up. AB - The objectives of this study were to evaluate the survival after 5 years of implants placed using inferior alveolar nerve (IAN) lateralization in cases of mandibular atrophy and to determine the incidence of complications. Twenty-seven patients received 74 implants by means of the IAN lateralization technique. Implant survival after 5 years of loading was 98.6%. Eighteen months after surgery, the recovery of sensitivity was complete in 26 cases. Implant placement with IAN lateralization was seen to be a satisfactory and predictable technique. IAN lateralization requires a high level of technical skill, and strict criteria should be applied when prescribing this treatment. PMID- 26837720 TI - Distinct set of chromosomal aberrations in childhood hepatocellular carcinoma is correlated to hepatitis B virus infection. AB - Hepatocellular carcinoma (HCC) is rarely observed in children and adolescents, but it is reported to be correlated with hepatitis B virus (HBV+) infections. This correlation is not easily explained, because in adults, HBV infections lead to the development of HCC only after decades, not within a few years. In HBV+ adulthood HCC, distinct chromosomal imbalances have been observed. Similar analyses have not been reported for childhood HCC. Here, we investigated whether chromosomal changes were associated with childhood HCC. We analysed formalin fixed paraffin-embedded (FFPE) samples derived from 17 patients, 0-18 years old, who underwent partial hepatectomies due to HBV+ or HBV- associated HCC. In parallel, in 15 cases, we also analysed non-neoplastic liver tissues adjacent to the HCC. All samples were analysed with high resolution, microarray-based, comparative genomic hybridisation (aCGH). Overall, genomic aberrations in childhood HCC resembled those reported for adulthood HCC. In HBV+ HCC samples, chromosomes 1, 6, 7, 9, 17, 19, and 22 were significantly changed compared to those in HBV- HCC samples. Most interestingly, aberrations for chromosomes 7, 8, 9, 11, and 19 were also observed in corresponding non-neoplastic samples. A specific set of chromosomal abnormalities, including gains in chromosomes 8q, 9q, 11q, and 19, was significantly enriched in HBV+ compared to HBV- non-neoplastic tissues. In childhood HCC, HBV+ was correlated to increased chromosomal instability and specific chromosomal imbalances. A subset of aberrations might be essential in HCC carcinogenesis because they occurred in adjacent, non-neoplastic tissues. In particular, the gain in chromosome 19 appeared to be highly important. PMID- 26837719 TI - 5-HT2 receptors mediate functional modulation of GABAa receptors and inhibitory synaptic transmissions in human iPS-derived neurons. AB - Neural progenitors differentiated from induced pluripotent stem cells (iPS) hold potentials for treating neurological diseases. Serotonin has potent effects on neuronal functions through multiple receptors, underlying a variety of neural disorders. Glutamate and GABA receptors have been proven functional in neurons differentiated from iPS, however, little is known about 5-HT receptor-mediated modulation in such neuronal networks. In the present study, human iPS were differentiated into cells possessing featured physiological properties of cortical neurons. Whole-cell patch-clamp recording was used to examine the involvement of 5-HT2 receptors in functional modulation of GABAergic synaptic transmission. We found that serotonin and DOI (a selective agonist of 5-HT2A/C receptor) reversibly reduced GABA-activated currents, and this 5-HT2A/C receptor mediated inhibition required G protein, PLC, PKC, and Ca(2+) signaling. Serotonin increased the frequency of miniature inhibitory postsynaptic currents (mIPSCs), which could be mimicked by alpha-methylserotonin, a 5-HT2 receptor agonist. In contrast, DOI reduced both frequency and amplitude of mIPSCs. These findings suggested that in iPS-derived human neurons serotonin postsynaptically reduced GABAa receptor function through 5-HT2A/C receptors, but presynaptically other 5 HT2 receptors counteracted the action of 5-HT2A/C receptors. Functional expression of serotonin receptors in human iPS-derived neurons provides a pre requisite for their normal behaviors after grafting. PMID- 26837721 TI - Mexico SimSmoke: how changes in tobacco control policies would impact smoking prevalence and smoking attributable deaths in Mexico. AB - We examined the effect of tobacco control policies in Mexico on smoking prevalence and smoking-related deaths using the Mexico SimSmoke model. The model is based on the previously developed SimSmoke simulation model of tobacco control policy, and uses population size, smoking rates and tobacco control policy data for Mexico. It assesses, individually, and in combination, the effect of six tobacco control policies on smoking prevalence and smoking-related deaths. Policies included: cigarette excise taxes, smoke-free laws, anti-smoking public education campaigns, marketing restrictions, access to tobacco cessation treatments and enforcement against tobacco sales youth. The model estimates that, if Mexico were to adopt strong tobacco control policies compared to current policy levels, smoking prevalence could be reduced by 30% in the next decade and by 50% by 2053; an additional 470,000 smoking-related premature deaths could be averted over the next 40 years. The greatest impact on smoking and smoking related deaths would be achieved by raising excise taxes on cigarettes from 55% to at least 70% of the retail price, followed by strong youth access enforcement and access to cessation treatments. Implementing tobacco control policies in Mexico could reduce smoking prevalence by 50%, and prevent 470,000 smoking related deaths by 2053. PMID- 26837722 TI - Failure to decolonize mupirocin and linezolid resistant MRSA from a patient with necrotizing soft tissue infection. AB - Colonization with methicillin resistant Staphylococcus aureus (MRSA) is considered to be a major risk factor for skin and soft tissue infections. We present a case of a patient suffering from necrotizing soft tissue infection and exposed to multiple antibiotics and developed colonization with linezolid resistant MRSA (LRMRSA). He could not be decolonized despite prolonged conventional or modified MRSA decolonization protocols. PMID- 26837723 TI - With regard about the case of Dengue, Chikungunya and Zika co-infection in a patient from Colombia. PMID- 26837724 TI - [Gastric adenomyoma clinically simulating hypertrophic pyloric stenosis]. AB - Gastric adenomyomas are extremely uncommon benign tumors in children. On histologic examination, these tumors have an epithelial component similar to pancreatic ducts. We present a case of a pyloric adenomyoma that clinically simulated hypertrophic pyloric stenosis in a newborn girl. Imaging tests, fundamentally magnetic resonance imaging, were very important in the characterization and diagnosis of this entity. PMID- 26837725 TI - ["Estereoataxia": an unacceptable term in technical Spanish]. PMID- 26837726 TI - Comments on the 2015 ESC Guidelines for the Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. PMID- 26837727 TI - Comments on the 2015 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension. PMID- 26837728 TI - 2015 ESC Guidelines for the Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. PMID- 26837729 TI - 2015 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension. PMID- 26837732 TI - The Role of Bronchoscopic Findings and Bronchoalveolar Lavage Fluid Cytology in Early Diagnosis of Ventilator-Associated Pneumonia. AB - BACKGROUND: Early diagnosis of ventilator-associated pneumonia (VAP) is necessary to reduce morbidity and improve survival of critically ill patients in the ICU. The purpose of the present study is to examine the performance of macroscopic bronchoscopic findings and cytological analysis of bronchoalveolar lavage fluid (BALF) as an early diagnostic tool for VAP, either alone or in combination with clinically oriented scores (modified Clinical Pulmonary Infection Score [CPIS] or Johanson criteria). METHODS: BAL was performed in 54 consecutive mechanically ventilated subjects. The predictive value of isolated or combined clinical characteristics, BALF, and/or other laboratory measurements in diagnosing VAP was analyzed by logistic regression analysis. A separate diagnostic score was derived from a linear combination of independent variables included in the multivariate model and compared with CPIS, Johanson criteria, and their combinations with BALF cytology (receiver operating characteristic curve analysis). RESULTS: Integrating relative neutrophil cell count in CPIS or Johanson criteria optimized their specificity (>80%) but decreased sensitivity (<70%). Radiographic progression and the presence of distal purulent secretions on bronchoscopy were independently associated with VAP diagnosis. A new score that incorporates clinical, radiographic, and early bronchoscopic findings presented excellent diagnostic accuracy (area under curve = 0.96, sensitivity 94.3%, specificity 84.2%). CONCLUSIONS: The diagnostic performance of classical clinical scores for VAP did not improve after combination with BALF cytology. A new composite score proved to be more accurate than previous scores in early VAP diagnosis. PMID- 26837734 TI - New Insights into the Epithelial-to-Mesenchymal Transition in Cancer. AB - The role of the epithelial-to-mesenchymal transition (EMT) in cancer progression is a long-debated issue. Recent evidence shows that EMT is not a prerequisite for cancer metastasis, but does confer chemoresistance. Future studies are needed to profile EMT events in different cancer types and under different circumstances to explore their potentials as therapeutic targets. PMID- 26837736 TI - Caught Red-Handed: Cycling Cardiomyocytes. PMID- 26837737 TI - Questions and Answers About Myostatin, GDF11, and the Aging Heart. PMID- 26837738 TI - New Insights Into miR-17-92 Cluster Regulation and Angiogenesis. PMID- 26837739 TI - Strip and Dress the Human Heart. PMID- 26837733 TI - APP Receptor? To Be or Not To Be. AB - Amyloid precursor protein (APP) and its metabolites play a key role in Alzheimer's disease pathogenesis. The idea that APP may function as a receptor has gained momentum based on its structural similarities to type I transmembrane receptors and the identification of putative APP ligands. We review the recent experimental evidence in support of this notion and discuss how this concept is viewed in the field. Specifically, we focus on the structural and functional characteristics of APP as a cell surface receptor, and on its interaction with adaptors and signaling proteins. We also address the importance of APP function as a receptor in Alzheimer's disease etiology and discuss how this function might be potentially important for the development of novel therapeutic approaches. PMID- 26837740 TI - Coronary Artery Disease and Its Risk Factors: Leveraging Shared Genetics to Discover Novel Biology. PMID- 26837741 TI - Most of the Dust Has Settled: cKit+ Progenitor Cells Are an Irrelevant Source of Cardiac Myocytes In Vivo. PMID- 26837744 TI - The Ubiquitin-Like SUMO System and Heart Function: From Development to Disease. AB - SUMOylation is a ubiquitin-related transient posttranslational modification pathway catalyzing the conjugation of small ubiquitin-like modifier (SUMO) proteins (SUMO1, SUMO2, and SUMO3) to lysine residues of proteins. SUMOylation targets a wide variety of cellular regulators and thereby affects a multitude of different cellular processes. SUMO/sentrin-specific proteases are able to remove SUMOs from targets, contributing to a tight control of SUMOylated proteins. Genetic and cell biological experiments indicate a critical role of balanced SUMOylation/deSUMOylation for proper cardiac development, metabolism, and stress adaptation. Here, we review the current knowledge about SUMOylation/deSUMOylation in the heart and provide an integrated picture of cardiac functions of the SUMO system under physiologic or pathologic conditions. We also describe potential therapeutic approaches targeting the SUMO machinery to combat heart disease. PMID- 26837743 TI - The Role of DNA Methylation in Cardiovascular Risk and Disease: Methodological Aspects, Study Design, and Data Analysis for Epidemiological Studies. AB - Epidemiological studies have demonstrated that genetic, environmental, behavioral, and clinical factors contribute to cardiovascular disease development. How these risk factors interact at the cellular level to cause cardiovascular disease is not well known. Epigenetic epidemiology enables researchers to explore critical links between genomic coding, modifiable exposures, and manifestation of disease phenotype. One epigenetic link, DNA methylation, is potentially an important mechanism underlying these associations. In the past decade, there has been a significant increase in the number of epidemiological studies investigating cardiovascular risk factors and outcomes in relation to DNA methylation, but many gaps remain in our understanding of the underlying cause and biological implications. In this review, we provide a brief overview of the biology and mechanisms of DNA methylation and its role in cardiovascular disease. In addition, we summarize the current evidence base in epigenetic epidemiology studies relevant to cardiovascular health and disease and discuss the limitations, challenges, and future directions of the field. Finally, we provide guidelines for well-designed epigenetic epidemiology studies, with particular focus on methodological aspects, study design, and analytical challenges. PMID- 26837742 TI - Emerging Concepts in Paracrine Mechanisms in Regenerative Cardiovascular Medicine and Biology. AB - In the past decade, substantial evidence supports the paradigm that stem cells exert their reparative and regenerative effects, in large part, through the release of biologically active molecules acting in a paracrine fashion on resident cells. The data suggest the existence of a tissue microenvironment where stem cell factors influence cell survival, inflammation, angiogenesis, repair, and regeneration in a temporal and spatial manner. PMID- 26837747 TI - Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis. AB - Atherosclerosis, for which hyperlipidemia is a major risk factor, is the leading cause of morbidity and mortality in Western society, and new therapeutic strategies are highly warranted. Brown adipose tissue (BAT) is metabolically active in human adults. Although positron emission tomography-computed tomography using a glucose tracer is the golden standard to visualize and quantify the volume and activity of BAT, it has become clear that activated BAT combusts fatty acids rather than glucose. Here, we review the role of brown and beige adipocytes in lipoprotein metabolism and atherosclerosis, with evidence derived from both animal and human studies. On the basis of mainly data from animal models, we propose a model in which activated brown adipocytes use their intracellular triglyceride stores to generate fatty acids for combustion. BAT rapidly replenishes these stores by internalizing primarily lipoprotein triglyceride derived fatty acids, generated by lipoprotein lipase-mediated hydrolysis of triglycerides, rather than by holoparticle uptake. As a consequence, BAT activation leads to the generation of lipoprotein remnants that are subsequently cleared via the liver provided that an intact apoE-low-density lipoprotein receptor pathway is present. Through these mechanisms, BAT activation reduces plasma triglyceride and cholesterol levels and attenuates diet-induced atherosclerosis development. Initial studies suggest that BAT activation in humans may also reduce triglyceride and cholesterol levels, but potential antiatherogenic effects should be assessed in future studies. PMID- 26837745 TI - From C-Reactive Protein to Interleukin-6 to Interleukin-1: Moving Upstream To Identify Novel Targets for Atheroprotection. AB - Plasma levels of the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) predict vascular risk with an effect estimate as large as that of total or high-density lipoprotein cholesterol. Further, randomized trial data addressing hsCRP have been central to understanding the anti-inflammatory effects of statin therapy and have consistently demonstrated on-treatment hsCRP levels to be as powerful a predictor of residual cardiovascular risk as on-treatment levels of low-density lipoprotein cholesterol. Yet, although hsCRP is clinically useful as a biomarker for risk prediction, most mechanistic studies suggest that CRP itself is unlikely to be a target for intervention. Moving upstream in the inflammatory cascade from CRP to interleukin (IL)-6 to IL-1 provides novel therapeutic opportunities for atheroprotection that focus on the central IL-6 signaling system and ultimately on inhibition of the IL-1beta-producing NOD-like receptor family pyrin domain containing 3 inflammasome. Cholesterol crystals, neutrophil extracellular traps, atheroprone flow, and local tissue hypoxia activate the NOD-like receptor family pyrin domain containing 3 inflammasome. As such, a unifying concept of hsCRP as a downstream surrogate biomarker for upstream IL-1beta activity has emerged. From a therapeutic perspective, small ischemia studies show reductions in acute-phase hsCRP production with the IL-1 receptor antagonist anakinra and the IL-6 receptor blocker tocilizumab. A phase IIb study conducted among diabetic patients at high vascular risk indicates that canakinumab, a human monoclonal antibody that targets IL-1beta, markedly reduces plasma levels of IL-6, hsCRP, and fibrinogen with little change in atherogenic lipids. Canakinumab in now being tested as a method to prevent recurrent cardiovascular events in a randomized trial of 10 065 post-myocardial infarction patients with elevated hsCRP that is fully enrolled and due to complete in 2017. Clinical trials using alternative anti-inflammatory agents active against the CRP/IL-6/IL-1 axis, including low-dose methotrexate and colchicine, are being explored. If successful, these trials will close the loop on the inflammatory hypothesis of atherosclerosis and serve as examples of how fundamental biologic principles can be translated into personalized medical practice. PMID- 26837750 TI - Equivalent linear damping characterization in linear and nonlinear force stiffness muscle models. AB - In the current research, the muscle equivalent linear damping coefficient which is introduced as the force-velocity relation in a muscle model and the corresponding time constant are investigated. In order to reach this goal, a 1D skeletal muscle model was used. Two characterizations of this model using a linear force-stiffness relationship (Hill-type model) and a nonlinear one have been implemented. The OpenSim platform was used for verification of the model. The isometric activation has been used for the simulation. The equivalent linear damping and the time constant of each model were extracted by using the results obtained from the simulation. The results provide a better insight into the characteristics of each model. It is found that the nonlinear models had a response rate closer to the reality compared to the Hill-type models. PMID- 26837748 TI - Zinc oxide and titanium dioxide nanoparticles induce oxidative stress, inhibit growth, and attenuate biofilm formation activity of Streptococcus mitis. AB - Streptococcus mitis from the oral cavity causes endocarditis and other systemic infections. Rising resistance against traditional antibiotics amongst oral bacteria further aggravates the problem. Therefore, antimicrobial and antibiofilm activities of zinc oxide and titanium dioxide nanoparticles (NPs) synthesized and characterized during this study against S. mitis ATCC 6249 and Ora-20 were evaluated in search of alternative antimicrobial agents. ZnO and TiO2-NPs exhibited an average size of 35 and 13 nm, respectively. The IC50 values of ZnO and TiO2-NPs against S. mitis ATCC 6249 were 37 and 77 ug ml(-1), respectively, while the IC50 values against S. mitis Ora-20 isolate were 31 and 53 ug ml(-1), respectively. Live and dead staining, biofilm formation on the surface of polystyrene plates, and extracellular polysaccharide production show the same pattern. Exposure to these nanoparticles also shows an increase (26-83 %) in super oxide dismutase (SOD) activity. Three genes, namely bapA1, sodA, and gtfB like genes from these bacteria were identified and sequenced for quantitative real-time PCR analysis. An increase in sodA gene (1.4- to 2.4-folds) levels and a decrease in gtfB gene (0.5- to 0.9-folds) levels in both bacteria following exposure to ZnO and TiO2-NPs were observed. Results presented in this study verify that ZnO-NPs and TiO2-NPs can control the growth and biofilm formation activities of these strains at very low concentration and hence can be used as alternative antimicrobial agents for oral hygiene. PMID- 26837749 TI - Exposure of aconitase to smoking-related oxidants results in iron loss and increased iron response protein-1 activity: potential mechanisms for iron accumulation in human arterial cells. AB - Smokers have an elevated risk of cardiovascular disease, but the origin(s) of this increased risk are incompletely defined. Evidence supports an accumulation of the oxidant-generating enzyme myeloperoxidase (MPO) in the inflamed artery wall, and smokers have high levels of SCN(-), a preferred MPO substrate, with this resulting in HOSCN formation. We hypothesised that HOSCN, a thiol-specific oxidant may target the iron-sulphur cluster of aconitase (both isolated, and within primary human coronary artery endothelial cells; HCAEC) resulting in enzyme dysfunction, release of iron, and conversion of the cytosolic isoform to iron response protein-1, which regulates intracellular iron levels. We show that exposure of isolated aconitase to increasing concentrations of HOSCN releases iron from the aconitase [Fe-S]4 cluster, and decreases enzyme activity. This is associated with protein thiol loss and modification of specific Cys residues in, and around, the [Fe-S]4 cluster. Exposure of HCAEC to HOSCN resulted in increased intracellular levels of chelatable iron, loss of aconitase activity and increased iron response protein-1 (IRP-1) activity. These data indicate HOSCN, an oxidant associated with oxidative stress in smokers, can induce aconitase dysfunction in human endothelial cells via Cys oxidation, damage to the [Fe-S]4 cluster, iron release and generation of IRP-1 activity, which modulates ferritin protein levels and results in dysregulation of iron metabolism. These data may rationalise, in part, the presence of increased levels of iron in human atherosclerotic lesions and contribute to increased oxidative damage and endothelial cell dysfunction in smokers. Similar reactions may occur at other sites of inflammation. PMID- 26837751 TI - Closed-loop firing rate regulation of two interacting excitatory and inhibitory neural populations of the basal ganglia. AB - This paper develops a new closed-loop firing rate regulation strategy for a population of neurons in the subthalamic nucleus, derived using a model-based analysis of the basal ganglia. The system is described using a firing rate model, in order to analyse the generation of beta-band oscillations. On this system, a proportional regulation of the firing rate reduces the gain of the subthalamo pallidal loop in the parkinsonian case, thus impeding pathological oscillation generation. A filter with a well-chosen frequency is added to this proportional scheme, in order to avoid a potential instability of the feedback loop due to actuation and measurement delays. Our main result is a set of conditions on the parameters of the stimulation strategy that guarantee both its stability and a prescribed delay margin. A discussion on the applicability of the proposed method and a complete set of mathematical proofs is included. PMID- 26837746 TI - The Human Microcirculation: Regulation of Flow and Beyond. AB - The microcirculation is responsible for orchestrating adjustments in vascular tone to match local tissue perfusion with oxygen demand. Beyond this metabolic dilation, the microvasculature plays a critical role in modulating vascular tone by endothelial release of an unusually diverse family of compounds including nitric oxide, other reactive oxygen species, and arachidonic acid metabolites. Animal models have provided excellent insight into mechanisms of vasoregulation in health and disease. However, there are unique aspects of the human microcirculation that serve as the focus of this review. The concept is put forth that vasculoparenchymal communication is multimodal, with vascular release of nitric oxide eliciting dilation and preserving normal parenchymal function by inhibiting inflammation and proliferation. Likewise, in disease or stress, endothelial release of reactive oxygen species mediates both dilation and parenchymal inflammation leading to cellular dysfunction, thrombosis, and fibrosis. Some pathways responsible for this stress-induced shift in mediator of vasodilation are proposed. This paradigm may help explain why microvascular dysfunction is such a powerful predictor of cardiovascular events and help identify new approaches to treatment and prevention. PMID- 26837752 TI - SUMO Pathway Modulation of Regulatory Protein Binding at the Ribosomal DNA Locus in Saccharomyces cerevisiae. AB - In this report, we identify cellular targets of Ulp2, one of two Saccharomyces cerevisiae small ubiquitin-related modifier (SUMO) proteases, and investigate the function of SUMO modification of these proteins. PolySUMO conjugates from ulp2Delta and ulp2Delta slx5Delta cells were isolated using an engineered affinity reagent containing the four SUMO-interacting motifs (SIMs) of Slx5, a component of the Slx5/Slx8 SUMO-targeted ubiquitin ligase (STUbL). Two proteins identified, Net1 and Tof2, regulate ribosomal DNA (rDNA) silencing and were found to be hypersumoylated in ulp2Delta,slx5Delta, and ulp2Delta slx5Delta cells. The increase in sumoylation of Net1 and Tof2 in ulp2Delta, but not ulp1ts cells, indicates that these nucleolar proteins are specific substrates of Ulp2 Based on quantitative chromatin-immunoprecipitation assays, both Net1 and Tof2 lose binding to their rDNA sites in ulp2Delta cells and both factors largely regain this association in ulp2Delta slx5Delta A parsimonious interpretation of these results is that hypersumoylation of these proteins causes them to be ubiquitylated by Slx5/Slx8, impairing their association with rDNA. Fob1, a protein that anchors both Net1 and Tof2 to the replication-fork barrier (RFB) in the rDNA repeats, is sumoylated in wild-type cells, and its modification levels increase specifically in ulp2Delta cells. Fob1 experiences a 50% reduction in rDNA binding in ulp2Delta cells, which is also rescued by elimination of Slx5 Additionally, overexpression of Sir2, another RFB-associated factor, suppresses the growth defect of ulp2Delta cells. Our data suggest that regulation of rDNA regulatory proteins by Ulp2 and the Slx5/Slx8 STUbL may be the cause of multiple ulp2Delta cellular defects. PMID- 26837753 TI - The Dissection of Expression Quantitative Trait Locus Hotspots. AB - Studies of the genetic loci that contribute to variation in gene expression frequently identify loci with broad effects on gene expression: expression quantitative trait locus hotspots. We describe a set of exploratory graphical methods as well as a formal likelihood-based test for assessing whether a given hotspot is due to one or multiple polymorphisms. We first look at the pattern of effects of the locus on the expression traits that map to the locus: the direction of the effects and the degree of dominance. A second technique is to focus on the individuals that exhibit no recombination event in the region, apply dimensionality reduction (e.g., with linear discriminant analysis), and compare the phenotype distribution in the nonrecombinant individuals to that in the recombinant individuals: if the recombinant individuals display a different expression pattern than the nonrecombinant individuals, this indicates the presence of multiple causal polymorphisms. In the formal likelihood-based test, we compare a two-locus model, with each expression trait affected by one or the other locus, to a single-locus model. We apply our methods to a large mouse intercross with gene expression microarray data on six tissues. PMID- 26837754 TI - Chromosome-Specific and Global Effects of Aneuploidy in Saccharomyces cerevisiae. AB - Aneuploidy, an unbalanced karyotype in which one or more chromosomes are present in excess or reduced copy number, causes an array of known phenotypes including proteotoxicity, genomic instability, and slowed proliferation. However, the molecular consequences of aneuploidy are poorly understood and an unbiased investigation into aneuploid cell biology is lacking. We performed high throughput screens for genes the deletion of which has a synthetic fitness cost in aneuploidy Saccharomyces cerevisiae cells containing single extra chromosomes. This analysis identified genes that, when deleted, decrease the fitness of specific disomic strains as well as those that impair the proliferation of a broad range of aneuploidies. In one case, a chromosome-specific synthetic growth defect could be explained fully by the specific duplication of a single gene on the aneuploid chromosome, highlighting the ability of individual dosage imbalances to cause chromosome-specific phenotypes in aneuploid cells. Deletion of other genes, particularly those involved in protein transport, however, confers synthetic sickness on a broad array of aneuploid strains. Indeed, aneuploid cells, regardless of karyotype, exhibit protein secretion and cell-wall integrity defects. Thus, we were able to use this screen to identify novel cellular consequences of aneuploidy, dependent on both specific chromosome imbalances and caused by many different aneuploid karyotypes. Interestingly, the vast majority of cancer cells are highly aneuploid, so this approach could be of further use in identifying both karyotype-specific and nonspecific stresses exhibited by cancer cells as potential targets for the development of novel cancer therapeutics. PMID- 26837757 TI - Immunopathology of mycobacterial diseases. PMID- 26837755 TI - SapTrap, a Toolkit for High-Throughput CRISPR/Cas9 Gene Modification in Caenorhabditis elegans. AB - In principle, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 allows genetic tags to be inserted at any locus. However, throughput is limited by the laborious construction of repair templates and guide RNA constructs and by the identification of modified strains. We have developed a reagent toolkit and plasmid assembly pipeline, called "SapTrap," that streamlines the production of targeting vectors for tag insertion, as well as the selection of modified Caenorhabditis elegans strains. SapTrap is a high-efficiency modular plasmid assembly pipeline that produces single plasmid targeting vectors, each of which encodes both a guide RNA transcript and a repair template for a particular tagging event. The plasmid is generated in a single tube by cutting modular components with the restriction enzyme SapI, which are then "trapped" in a fixed order by ligation to generate the targeting vector. A library of donor plasmids supplies a variety of protein tags, a selectable marker, and regulatory sequences that allow cell-specific tagging at either the N or the C termini. All site specific sequences, such as guide RNA targeting sequences and homology arms, are supplied as annealed synthetic oligonucleotides, eliminating the need for PCR or molecular cloning during plasmid assembly. Each tag includes an embedded Cbr-unc 119 selectable marker that is positioned to allow concurrent expression of both the tag and the marker. We demonstrate that SapTrap targeting vectors direct insertion of 3- to 4-kb tags at six different loci in 10-37% of injected animals. Thus SapTrap vectors introduce the possibility for high-throughput generation of CRISPR/Cas9 genome modifications. PMID- 26837758 TI - Nuclear cardiology in the literature: A selection of recent, original research papers. PMID- 26837756 TI - TRP channels and traffic-related environmental pollution-induced pulmonary disease. AB - Environmental pollutant exposures are major risk factors for adverse health outcomes, with increased morbidity and mortality in humans. Diesel exhaust (DE) is one of the major harmful components of traffic-related air pollution. Exposure to DE affects several physiological systems, including the airways, and pulmonary diseases are increased in highly populated urban areas. Hence, there are urgent needs to (1) create newer and lesser polluting fuels, (2) improve exhaust aftertreatments and reduce emissions, and (3) understand mechanisms of actions for toxic effects of both conventional and cleaner diesel fuels on the lungs. These steps could aid the development of diagnostics and interventions to prevent the negative impact of traffic-related air pollution on the pulmonary system. Exhaust from conventional, and to a lesser extent, clean fuels, contains particulate matter (PM) and more than 400 additional chemical constituents. The major toxic constituents are nitrogen oxides (NOx) and polycyclic aromatic hydrocarbons (PAHs). PM and PAHs could potentially act via transient receptor potential (TRP) channels. In this review, we will first discuss the associations between DE from conventional as well as clean fuel technologies and acute and chronic airway inflammation. We will then review possible activation and/or potentiation of TRP vanilloid type 1 (TRPV1) and ankyrin 1 (TRPA1) channels by PM and PAHs. Finally, we will discuss and summarize recent findings on the mechanisms whereby TRPs could control the link between DE and airway inflammation, which is a primary determinant leading to pulmonary disease. PMID- 26837759 TI - Activated KRAS Cooperates with MLL-AF4 to Promote Extramedullary Engraftment and Migration of Cord Blood CD34+ HSPC But Is Insufficient to Initiate Leukemia. AB - The MLL-AF4 (MA4) fusion gene is the genetic hallmark of an aggressive infant pro B-acute lymphoblastic leukemia (B-ALL). Our understanding of MA4-mediated transformation is very limited. Whole-genome sequencing studies revealed a silent mutational landscape, which contradicts the aggressive clinical outcome of this hematologic malignancy. Only RAS mutations were recurrently detected in patients and found to be associated with poorer outcome. The absence of MA4-driven B-ALL models further questions whether MA4 acts as a single oncogenic driver or requires cooperating mutations to manifest a malignant phenotype. We explored whether KRAS activation cooperates with MA4 to initiate leukemia in cord blood derived CD34(+) hematopoietic stem/progenitor cells (HSPC). Clonogenic and differentiation/proliferation assays demonstrated that KRAS activation does not cooperate with MA4 to immortalize CD34(+) HSPCs. Intrabone marrow transplantation into immunodeficient mice further showed that MA4 and KRAS(G12V) alone or in combination enhanced hematopoietic repopulation without impairing myeloid lymphoid differentiation, and that mutated KRAS did not cooperate with MA4 to initiate leukemia. However, KRAS activation enhanced extramedullary hematopoiesis of MA4-expressing cell lines and CD34(+) HSPCs that was associated with leukocytosis and central nervous system infiltration, both hallmarks of infant t(4;11)(+) B-ALL. Transcriptional profiling of MA4-expressing patients supported a cell migration gene signature underlying the mutant KRAS-mediated phenotype. Collectively, our findings demonstrate that KRAS affects the homeostasis of MA4 expressing HSPCs, suggesting that KRAS activation in MA4(+) B-ALL is important for tumor maintenance rather than initiation. Cancer Res; 76(8); 2478-89. (c)2016 AACR. PMID- 26837761 TI - Pharmacological Inhibition of the Histone Lysine Demethylase KDM1A Suppresses the Growth of Multiple Acute Myeloid Leukemia Subtypes. AB - Lysine-specific demethylase 1 (KDM1A) is a transcriptional coregulator that can function in both the activation and repression of gene expression, depending upon context. KDM1A plays an important role in hematopoiesis and was identified as a dependency factor in leukemia stem cell populations. Therefore, we investigated the consequences of inhibiting KDM1A in a panel of cell lines representing all acute myelogenous leukemia (AML) subtypes using selective, reversible and irreversible KDM1A small-molecule inhibitors. Cell models of AML, CML, and T-ALL were potently affected by KDM1A inhibition, and cells bearing RUNX1-RUNX1T1 (AML1 ETO) translocations were especially among the most sensitive. RNAi-mediated silencing of KDM1A also effectively suppressed growth of RUNX1-RUNX1T1-containing cell lines. Furthermore, pharmacologic inhibition of KDM1A resulted in complete abrogation of tumor growth in an AML xenograft model harboring RUNX1-RUNX1T1 translocations. We unexpectedly found that KDM1A-targeting compounds not only inhibited the catalytic activity of the enzyme, but evicted KDM1A from target genes. Accordingly, compound-mediated KDM1A eviction was associated with elevated levels of local histone H3 lysine 4 dimethylation, and increased target gene expression, which was further accompanied by cellular differentiation and induction of cell death. Finally, our finding that KDM1A inhibitors effectively synergize with multiple conventional as well as candidate anti-AML agents affords a framework for potential future clinical application. Cancer Res; 76(7); 1975 88. (c)2016 AACR. PMID- 26837760 TI - G0S2 Suppresses Oncogenic Transformation by Repressing a MYC-Regulated Transcriptional Program. AB - Methylation-mediated silencing of G0-G1 switch gene 2 (G0S2) has been detected in a variety of solid tumors, whereas G0S2 induction is associated with remissions in patients with acute promyelocytic leukemia, implying that G0S2 may possess tumor suppressor activity. In this study, we clearly demonstrate that G0S2 opposes oncogene-induced transformation using G0s2-null immortalized mouse embryonic fibroblasts (MEF). G0s2-null MEFs were readily transformed with HRAS or EGFR treatment compared with wild-type MEFs. Importantly, restoration of G0S2 reversed HRAS-driven transformation. G0S2 is known to regulate fat metabolism by attenuating adipose triglyceride lipase (ATGL), but repression of oncogene induced transformation by G0S2 was independent of ATGL inhibition. Gene expression analysis revealed an upregulation of gene signatures associated with transformation, proliferation, and MYC targets in G0s2-null MEFs. RNAi-mediated ablation and pharmacologic inhibition of MYC abrogated oncogene-induced transformation of G0s2-null MEFs. Furthermore, we found that G0S2 was highly expressed in normal breast tissues compared with malignant tissue. Intriguingly, high levels of G0S2 were also associated with a decrease in breast cancer recurrence rates, especially in estrogen receptor-positive subtypes, and overexpression of G0S2 repressed the proliferation of breast cancer cells in vitro. Taken together, these findings indicate that G0S2 functions as a tumor suppressor in part by opposing MYC activity, prompting further investigation of the mechanisms by which G0S2 silencing mediates MYC-induced oncogenesis in other malignancies. PMID- 26837762 TI - ILK Induction in Lymphoid Organs by a TNFalpha-NF-kappaB-Regulated Pathway Promotes the Development of Chronic Lymphocytic Leukemia. AB - The proliferation of chronic lymphocytic leukemia (CLL) cells requires communication with the lymphoid organ microenvironment. Integrin-linked kinase (ILK) is a multifunctional intracellular adaptor protein that transmits extracellular signals to regulate malignant cell motility, metastasis, and cell cycle progression, but is poorly characterized in hematologic malignancies. In this study, we investigated the role of ILK in the context of CLL and observed high ILK expression in patient samples, particularly in tumor cells harboring prognostic high-risk markers such as unmutated IGHV genes, high Zap70, or CD38 expression, or a signature of recent proliferation. We also found increased numbers of Ki67 (MKI67)-positive cells in regions of enhanced ILK expression in lymph nodes from CLL patients. Using coculture conditions mimicking the proliferative lymph node microenvironment, we detected a parallel induction of ILK and cyclin D1 (CCND1) expression in CLL cells that was dependent on the activation of NF-kappaB signaling by soluble TNFalpha. The newly synthesized ILK protein colocalized to centrosomal structures and was required for correct centrosome clustering and mitotic spindle organization. Furthermore, we established a mouse model of CLL in which B-cell-specific genetic ablation of ILK resulted in decelerated leukemia development due to reduced organ infiltration and proliferation of CLL cells. Collectively, our findings describe a TNFalpha-NF kappaB-mediated mechanism by which ILK expression is induced in the lymph node microenvironment and propose that ILK promotes leukemogenesis by enabling CLL cells to cope with centrosomal defects acquired during malignant transformation. Cancer Res; 76(8); 2186-96. (c)2016 AACR. PMID- 26837764 TI - Stomach-Specific Activation of Oncogenic KRAS and STAT3-Dependent Inflammation Cooperatively Promote Gastric Tumorigenesis in a Preclinical Model. AB - About 5% to 10% of human gastric tumors harbor oncogenic mutations in the KRAS pathway, but their presence alone is often insufficient for inducing gastric tumorigenesis, suggesting a requirement for additional mutagenic events or microenvironmental stimuli, including inflammation. Assessing the contribution of such events in preclinical mouse models requires Cre recombinase-mediated conditional gene expression in stem or progenitor cells of normal and transformed gastric epithelium. We therefore constructed a bacterial artificial chromosome containing transgene (Tg), comprising the regulatory elements of the trefoil factor 1 (Tff1) gene and the tamoxifen-inducible Cre recombinase (CreERT2)-coding sequence. The resulting Tg(Tff1-CreERT2) mice were crossed with mice harboring conditional oncogenic mutations in Kras or Braf The administration of tamoxifen to the resulting adult Tg(Tff1-CreERT2);Kras(LSL-G12D/+) and Tg(Tff1 CreERT2);Braf(LSL-V600E/+) mice resulted in gastric metaplasia, inflammation, and adenoma development, characterized by excessive STAT3 activity. To assess the contribution of STAT3 to the spontaneously developing gastric adenomas in gp130(F/F) mice, which carry a knockin mutation in the Il6 signal transducer (Il6st), we generated Tg(Tff1-CreERT2);Stat3(fl/fl);gp130(F/F) mice that also harbor a conditional Stat3 knockout allele and found that tamoxifen administration conferred a significant reduction in their tumor burden. Conversely, excessive Kras activity in Tg(Tff1-CreERT2);Kras(LSL G12D/+);gp130(F/F) mice promoted more extensive gastric inflammation, metaplastic transformation, and tumorigenesis than observed in Tg(Tff1-CreERT2);Kras(LSL G12D/+) mice. Collectively, our findings demonstrate that advanced gastric tumorigenesis requires oncogenic KRAS or BRAF in concert with aberrant STAT3 activation in epithelial precursor cells of the glandular stomach, providing a new conditional model of gastric cancer in which to investigate candidate therapeutic targets and treatment strategies. Cancer Res; 76(8); 2277-87. (c)2016 AACR. PMID- 26837763 TI - Galectin-3 Cleavage Alters Bone Remodeling: Different Outcomes in Breast and Prostate Cancer Skeletal Metastasis. AB - Management of bone metastasis remains clinically challenging and requires the identification of new molecular target(s) that can be therapeutically exploited to improve patient outcome. Galectin-3 (Gal-3) has been implicated as a secreted factor that alters the bone microenvironment. Proteolytic cleavage of Gal-3 may also contribute to malignant cellular behaviors, but has not been addressed in cancer metastasis. Here, we report that Gal-3 modulates the osteolytic bone tumor microenvironment in the presence of RANKL. Gal-3 was localized on the osteoclast cell surface, and its suppression by RNAi or a specific antagonist markedly inhibited osteoclast differentiation markers, including tartrate-resistant acid phosphatase, and reduced the number of mature osteoclasts. Structurally, the 158 175 amino acid sequence in the carbohydrate recognition domain (CRD) of Gal-3 was responsible for augmented osteoclastogenesis. During osteoclast maturation, Gal-3 interacted and colocalized with myosin-2A along the surface of cell-cell fusion. Pathologically, bone metastatic cancers expressed and released an intact form of Gal-3, mainly detected in breast cancer bone metastases, as well as a cleaved form, more abundant in prostate cancer bone metastases. Secreted intact Gal-3 interacted with myosin-2A, leading to osteoclastogenesis, whereas a shift to cleaved Gal-3 attenuated the enhancement in osteoclast differentiation. Thus, our studies demonstrate that Gal-3 shapes the bone tumor microenvironment through distinct roles contingent on its cleavage status, and highlight Gal-3 targeting through the CRD as a potential therapeutic strategy for mitigating osteolytic bone remodeling in the metastatic niche. PMID- 26837765 TI - Phytoestrogen Suppresses Efflux of the Diagnostic Marker Protoporphyrin IX in Lung Carcinoma. AB - One promising method to visualize cancer cells is based on the detection of the fluorescent photosensitizer protoporphyrin IX (PpIX) synthesized from 5 aminolevulinic acid (ALA), but this method cannot be used in cancers that exhibit poor PpIX accumulation. PpIX appears to be pumped out of cancer cells by the ABC transporter G2 (ABCG2), which is associated with multidrug resistance. Genistein is a phytoestrogen that appears to competitively inhibit ABCG2 activity. Therefore, we investigated whether genistein can promote PpIX accumulation in human lung carcinoma cells. Here we report that treatment of A549 lung carcinoma cells with genistein or a specific ABCG2 inhibitor promoted ALA-mediated accumulation of PpIX by approximately 2-fold. ABCG2 depletion and overexpression studies further revealed that genistein promoted PpIX accumulation via functional repression of ABCG2. After an extended period of genistein treatment, a significant increase in PpIX accumulation was observed in A549 cells (3.7-fold) and in other cell lines. Systemic preconditioning with genistein in a mouse xenograft model of lung carcinoma resulted in a 1.8-fold increase in accumulated PpIX. Long-term genistein treatment stimulated the expression of genes encoding enzymes involved in PpIX synthesis, such as porphobilinogen deaminase, uroporphyrinogen decarboxylase, and protoporphyrinogen oxidase. Accordingly, the rate of PpIX synthesis was also accelerated by genistein pretreatment. Thus, our results suggest that genistein treatment effectively enhances ALA-induced PpIX accumulation by preventing the ABCG2-mediated efflux of PpIX from lung cancer cells and may represent a promising strategy to improve ALA-based diagnostic approaches in a broader set of malignancies. Cancer Res; 76(7); 1837-46. (c)2016 AACR. PMID- 26837768 TI - Oxygen-Enhanced MRI Is a Major Advance in Tumor Hypoxia Imaging. PMID- 26837767 TI - Hypoxia-Induced Epithelial-to-Mesenchymal Transition in Hepatocellular Carcinoma Induces an Immunosuppressive Tumor Microenvironment to Promote Metastasis. AB - Portal vein tumor thrombosis (PVTT) is a significant risk factor for metastasis in hepatocellular carcinoma (HCC) patients and is therefore associated with poor prognosis. The presence of PVTT frequently accompanies substantial hypoxia within the tumor microenvironment, which is suggested to accelerate tumor metastasis, but it is unclear how this occurs. Recent evidence has shown that the hypoxia inducible factor HIF-1alpha induces epithelial-to-mesenchymal transition (EMT) in tumor cells to facilitate metastasis. In this study, we investigated whether hypoxia-induced EMT in cancer cells also affects immune cells in the tumor microenvironment to promote immunosuppression. We found that hypoxia-induced EMT increased the expression of the CCL20 cytokine in hepatoma cells. Furthermore, coculture of monocyte-derived macrophages with hypoxic hepatoma cells revealed that the expression of indoleamine 2, 3-dioxygenase (IDO) was induced in monocyte derived macrophages in a CCL20-dependent manner. In turn, these IDO-expressing monocyte-derived macrophages suppressed T-cell proliferation and promoted the expansion of immunosuppressive regulatory T cells. Moreover, high CCL20 expression in HCC specimens was associated with PVTT and poor patient survival. Collectively, our findings suggest that the HIF-1alpha/CCL20/IDO axis in hepatocellular carcinoma is important for accelerating tumor metastasis through both the induction of EMT and the establishment of an immunosuppressive tumor microenvironment, warranting further investigation into the therapeutic effects of blocking specific nodes of this signaling network. PMID- 26837766 TI - Mesenchymal Tumorigenesis Driven by TSC2 Haploinsufficiency Requires HMGA2 and Is Independent of mTOR Pathway Activation. AB - Tuberous sclerosis (TSC) is a tumor suppressor gene syndrome that is associated with the widespread development of mesenchymal tumor types. Genetically, TSC is said to occur through a classical biallelic inactivation of either TSC genes (TSC1, hamartin or TSC2, tuberin), an event that is implicated in the induction of the mTOR pathway and subsequent tumorigenesis. High Mobility Group A2 (HMGA2), an architectural transcription factor, is known to regulate mesenchymal differentiation and drive mesenchymal tumorigenesis in vivo. Here, we investigated the role of HMGA2 in the pathogenesis of TSC using the TSC2(+/-) mouse model that similarly mirrors human disease and human tumor samples. We show that HMGA2 expression was detected in 100% of human and mouse TSC tumors and that HMGA2 activation was required for TSC mesenchymal tumorigenesis in genetically engineered mouse models. In contrast to the current dogma, the mTOR pathway was not activated in all TSC2(+/-) tumors and was elevated in only 50% of human mesenchymal tumors. Moreover, except for a subset of kidney tumors, tuberin was expressed in both human and mouse tumors. Therefore, haploinsufficiency of one TSC tumor suppressor gene was required for tumor initiation, but further tumorigenesis did not require the second hit, as previously postulated. Collectively, these findings demonstrate that tissue-specific genetic mechanisms are employed to promote tumor pathogenesis in TSC and identify a novel, critical pathway for potential therapeutic targeting. PMID- 26837769 TI - Oncogenic Fusion Gene CD74-NRG1 Confers Cancer Stem Cell-like Properties in Lung Cancer through a IGF2 Autocrine/Paracrine Circuit. AB - The CD74-Neuregulin1 (NRG1) fusion gene was recently identified as novel driver of invasive mucinous adenocarcinoma, a malignant form of lung cancer. However, the function of the CD74-NRG1 fusion gene in adenocarcinoma pathogenesis and the mechanisms by which it may impart protumorigenic characteristics to cancer stem cells (CSC) is still unclear. In this study, we found that the expression of the CD74-NRG1 fusion gene increased the population of lung cancer cells with CSC-like properties. CD74-NRG1 expression facilitated sphere formation not only of cancer cells, but also of nonmalignant lung epithelial cells. Using a limiting dilution assay in a xenograft model, we further show that the CD74-NRG1 fusion gene enhanced tumor initiation. Mechanistically, we found that CD74-NRG1 expression promoted the phosphorylation of ErbB2/3 and activated the PI3K/Akt/NF-kappaB signaling pathway. Furthermore, the expression of the secreted insulin-like growth factor 2 (IGF2) and phosphorylation of its receptor, IGF1R, were enhanced in an NF-kappaB-dependent manner in cells expressing CD74-NRG1. These findings suggest that CD74-NRG1-induced NF-kappaB activity promotes the IGF2 autocrine/paracrine circuit. Moreover, inhibition of ErbB2, PI3K, NF-kappaB, or IGF2 suppressed CD74-NRG1-induced tumor sphere formation. Therefore, our study provides a preclinical rationale for developing treatment approaches based on these identified pathways to suppress CSC properties that promote tumor progression and recurrence. PMID- 26837771 TI - The Difficulties of Informed Consent in Stem Cell Transplant. AB - Informed consent is the process by which a competent patient is provided with a sufficient amount of relevant information to make an educated decision about a procedure. The process of informed consent is designed to prioritize patients' autonomy. Stem cell transplant (SCT) is a complicated process with many possible results and requirements for on-going decision-making depending on outcomes and complications. While understanding basic theories of decision science will help the physician provide improved information at the time of consent, experiential learning by the patients as they proceed through SCT may have the strongest influence in continued patient decision-making that may or may not align with their initial informed consent. PMID- 26837770 TI - Effects of Anticancer Drugs on Chromosome Instability and New Clinical Implications for Tumor-Suppressing Therapies. AB - Whole chromosomal instability (CIN), manifested as unequal chromosome distribution during cell division, is a distinguishing feature of most cancer types. CIN is generally considered to drive tumorigenesis, but a threshold level exists whereby further increases in CIN frequency in fact hinder tumor growth. While this attribute is appealing for therapeutic exploitation, drugs that increase CIN beyond this therapeutic threshold are currently limited. In our previous work, we developed a quantitative assay for measuring CIN based on the use of a nonessential human artificial chromosome (HAC) carrying a constitutively expressed EGFP transgene. Here, we used this assay to rank 62 different anticancer drugs with respect to their effects on chromosome transmission fidelity. Drugs with various mechanisms of action, such as antimicrotubule activity, histone deacetylase inhibition, mitotic checkpoint inhibition, and targeting of DNA replication and damage responses, were included in the analysis. Ranking of the drugs based on their ability to induce HAC loss revealed that paclitaxel, gemcitabine, dactylolide, LMP400, talazoparib, olaparib, peloruside A, GW843682, VX-680, and cisplatin were the top 10 drugs demonstrating HAC loss at a high frequency. Therefore, identification of currently used compounds that greatly increase chromosome mis-segregation rates should expedite the development of new therapeutic strategies to target and leverage the CIN phenotype in cancer cells. PMID- 26837772 TI - The effect of rapamycin on TGFbeta1 and MMP1 expression in a rabbit model of urethral stricture. AB - PURPOSE: To investigate the effect of rapamycin on TGFbeta1 and MMP1 expression in a rabbit model of urethral stricture. METHODS: Twenty-four adult New Zealand male rabbits underwent an electrocoagulation of the bulbar urethra with a 13Fr pediatric resectoscope. Then rabbits were randomly divided into three groups: (1) normal control group: normal saline (NS), (2) the vehicle control group: dimethyl sulfoxide (DMSO), and (3) the treatment group: effective-dose rapamycin in DMSO (Ra), with 12, 6, and 6 rabbits in each group, respectively. Drugs were given by urethral irrigation daily for 4 weeks. Urethral tissue was harvested for histological and molecular analyses. TGFbeta1 and MMP1 expression levels were evaluated by real-time quantitative PCR and immunohistochemistry. RESULTS: Ten, six, and six rabbits were evaluated finally in Ra, DMSO, and NS group, respectively. Histological examination revealed the distribution of fibrosis and the degree of collagen deposition in the Ra group were smaller and slighter than the two control groups. Collagen content was significantly less in the Ra group than in the DMSO group (P < 0.001) and the NS group (P < 0.001). qRT-PCR analysis showed a higher expression of MMP1 mRNA in the Ra group than in the DMSO group (P < 0.001) and the NS group (P < 0.001). Immunohistochemistry showed the protein levels of MMP1 in the Ra group were significantly increased when compared with the DMSO group (P < 0.01) and the NS group (P < 0.01). On the other hand, no statistical difference could be found between every two groups in both mRNA and protein levels of TGFbeta1. CONCLUSIONS: Rapamycin enhances the expression of MMP1 in a rabbit model of urethral stricture, but has no direct effect on the expression of TGFbeta1. PMID- 26837774 TI - Spontaneous, Defect-Free Kinking via Capillary Instability during Vapor-Liquid Solid Nanowire Growth. AB - Kinking, a common anomaly in nanowire (NW) vapor-liquid-solid (VLS) growth, represents a sudden change of the wire's axial growth orientation. This study focuses on defect-free kinking during germanium NW VLS growth, after nucleation on a Ge (111) single crystal substrate, using Au-Ge catalyst liquid droplets of defined size. Statistical analysis of the fraction of kinked NWs reveals the dependence of kinking probability on the wire diameter and the growth temperature. The morphologies of kinked Ge NWs studied by electron microscopy show two distinct, defect-free, kinking modes, whose underlying mechanisms are explained with the help of 3D multiphase field simulations. Type I kinking, in which the growth axis changes from vertical [111] to ?110?, was observed in Ge NWs with a nominal diameter of ~ 20 nm. This size coincides with a critical diameter at which a spontaneous transition from ?111? to ?110? growth occurs in the phase field simulations. Larger diameter NWs only exhibit Type II kinking, in which the growth axis changes from vertical [111] directly to an inclined ?111? axis during the initial stages of wire growth. This is caused by an error in sidewall facet development, which produces a shrinkage in the area of the (111) growth facet with increasing NW length, causing an instability of the Au-Ge liquid droplet at the tip of the NW. PMID- 26837773 TI - Overexpression of CXCL3 can enhance the oncogenic potential of prostate cancer. AB - PURPOSE: CXCL3 and its receptor CXCR2 were considered to play particularly important roles in the progression of malignancies. However, the investigations about CXCL3/CXCR2 axis in prostate cancer have been poorly involved. Herein we firstly reported our studies on the expression and biological roles of CXCL3 and CXCR2 in prostate cancer. METHODS: Expression levels of CXCL3 and CXCR2 in prostate cancer cell lines (PC-3, DU145 and LNCaP), immortalized prostate stromal cell line (WPMY-1) and immortalized prostate epithelial cell line (RWPE-1) were investigated by RT-PCR, ELISA and western blot, whereas expression levels of CXCL3 in a prostate tissue microarray were detected by immunohistochemistry. Cell counting kit-8 and transwell assays were, respectively, utilized to determine the effects of exogenous CXCL3 on the cell proliferation and migration. We further examined whether CXCL3 could regulate the expression of genes correlated with prostate tumorigenesis by RT- PCR. RESULTS: Elevated expression of CXCR2 was detected in DU145, LNCaP and RWPE-1. Moreover, high-level CXCL3 can be secreted by PC-3 and RWPE-1, and CXCL3 protein expression level in tissue microarray is concordant with prostate cancer metastasis. Exogenous CXCL3 does not contribute to proliferation, but has a significant effect on migration of prostate cancer cells and RWPE-1. Finally, our data showed that exogenous CXCL3 can regulate the expression of genes including ERK, TP73, NUMB, BAX and NDRG3. CONCLUSION: Our findings suggest that CXCL3 and its receptor CXCR2 are overexpressed in prostate cancer cells, prostate epithelial cells and prostate cancer tissues, which may play multiple roles in prostate cancer progression and metastasis. PMID- 26837776 TI - Endometriosis and infertility. AB - Endometriosis remains a very enigmatic and perplexing disease. The exact mechanism by which endometriosis causes infertility is still unclear. In the present paper, we will review possible mechanisms leading to subfertility or infertility in women with endometriosis and examine them according to location. Endometriosis in the pelvic cavity is a pathology associated with a general inflammatory response and should therefore be considered an inflammatory disease. Inflammatory changes affect the peritoneal fluid and hence the intratubal milieu, since the ampulla (where fertilization takes place) is exposed to peritoneal fluid through the fimbria. Any inflammatory change at this level may therefore impact fertilization and natural conception. The relationship between ovarian endometriomas and infertility may, of course, be explained by the presence of periovarian endometriosis. In the ovary, fibrosis observed in some cortical areas is induced by the inflammatory reaction caused by the presence of endometriomas. The association between fibrosis and a reduced ovarian reserve was demonstrated. Upregulated recruitment and the subsequent demise of early follicles may result in focal exhaustion of primordial follicles. Burn-out of early follicles by a local pelvic inflammatory environment caused by endometriomas may therefore be suggested. However, intraovarian inflammation, subsequent fibrosis and depletion of the ovarian reserve constitute another reason that should also be given due consideration. In addition, surgery should not be ruled out as a possible cause of ovarian reserve depletion. In conclusion, potential mechanisms leading to infertility are numerous, and while some of them remain hypothetical for now, others are supported by clear evidence. These possible mechanisms were reviewed in the present paper. PMID- 26837777 TI - Effect of oxygen supply on the size of implantable islet-containing encapsulation devices. AB - Beta-cell replacement therapy is a promising approach for the treatment of diabetes but is currently limited by the human islet availability and by the need for systemic immunosuppression. Tissue engineering approaches that will enable the utilization of islets or beta-cells from alternative sources (such as porcine islets or human stem cell derived beta cells) and minimize or eliminate the need for immunosuppression have the potential to address these critical limitations. However, tissue engineering approaches are critically hindered by the device size (similar to the size of a large flat screen television) required for efficacy in humans. The primary factor dictating the device size is the oxygen availability to islets to support their viability and function (glucose-stimulated insulin secretion [GSIS]). GSIS is affected (inhibited) at a much higher oxygen partial pressure [pO2] than that of viability (e.g. 10 mmHg as opposed to 0.1 mmHg). Enhanced oxygen supply (higher pO2) than what is available in vivo at transplant sites can have a profound effect on the required device size (potentially reduce it to the size of a postage stamp). This paper summarizes key information on the effect of oxygen on islet viability and function within immunoisolation devices and describes the potential impact of enhanced oxygen supply to devices in vivo on device size reduction. PMID- 26837775 TI - Methods and strategies for assessing uncontrolled drug-drug interactions in population pharmacokinetic analyses: results from the International Society of Pharmacometrics (ISOP) Working Group. AB - The purpose of this work was to present a consolidated set of guidelines for the analysis of uncontrolled concomitant medications (ConMed) as a covariate and potential perpetrator in population pharmacokinetic (PopPK) analyses. This white paper is the result of an industry-academia-regulatory collaboration. It is the recommendation of the working group that greater focus be given to the analysis of uncontrolled ConMeds as part of a PopPK analysis of Phase 2/3 data to ensure that the resulting outcome in the PopPK analysis can be viewed as reliable. Other recommendations include: (1) collection of start and stop date and clock time, as well as dose and frequency, in Case Report Forms regarding ConMed administration schedule; (2) prespecification of goals and the methods of analysis, (3) consideration of alternate models, other than the binary covariate model, that might more fully characterize the interaction between perpetrator and victim drug, (4) analysts should consider whether the sample size, not the percent of subjects taking a ConMed, is sufficient to detect a ConMed effect if one is present and to consider the correlation with other covariates when the analysis is conducted, (5) grouping of ConMeds should be based on mechanism (e.g., PGP inhibitor) and not drug class (e.g., beta-blocker), and (6) when reporting the results in a publication, all details related to the ConMed analysis should be presented allowing the reader to understand the methods and be able to appropriately interpret the results. PMID- 26837778 TI - Electrospun mat with eyelid fat-derived stem cells as a scaffold for ocular epithelial regeneration. AB - The aim of this study was to develop nanofibrous gelatin substrates for eyelid fat stem cell (EFSC) expansion that can serve as a potential alternative substrate to replace human amniotic membrane. Biocompatibility results indicated that all substrates were highly biocompatible, as EFSCs could favorably attach and proliferate on the nanofibrous surfaces. Microscopic figures showed that the EFSC were firmly anchored to the substrates and were able to retain a normal stem cell phenotype. Immunocytochemistry (ICC) and real time-PCR results revealed change in the expression profile of EFSCs grown on nanofibrous substrates when compared to those grown on control in epithelial induction condition. In addition, electrospun gelatin mats especially oriented scaffold provides not only a milieu supporting EFSCs expansion, but also serves as a useful alternative carrier for ocular surface tissue engineering and could be used as an alternative substrate to amniotic membrane. PMID- 26837779 TI - A phylogenomic reappraisal of family-level divisions within the class Halobacteria: proposal to divide the order Halobacteriales into the families Halobacteriaceae, Haloarculaceae fam. nov., and Halococcaceae fam. nov., and the order Haloferacales into the families, Haloferacaceae and Halorubraceae fam nov. AB - The evolutionary interrelationships between the archaeal organisms which comprise the class Halobacteria have proven difficult to elucidate using traditional phylogenetic tools. The class currently contains three orders. However, little is known about the family level relationships within these orders. In this work, we have completed a comprehensive comparative analysis of 129 sequenced genomes from members of the class Halobacteria in order to identify shared molecular characteristics, in the forms of conserved signature insertions/deletions (CSIs) and conserved signature proteins (CSPs), which can provide reliable evidence, independent of phylogenetic trees, that the species from the groups in which they are found are specifically related to each other due to common ancestry. Here we present 20 CSIs and 31 CSPs which are unique characteristics of infra-order level groups of genera within the class Halobacteria. We also present 40 CSIs and 234 CSPs which are characteristic of Haloarcula, Halococcus, Haloferax, or Halorubrum. Importantly, the CSIs and CSPs identified here provide evidence that the order Haloferacales contains two main groups, one consisting of Haloferax and related genera supported by four CSIs and five CSPs and the other consisting of Halorubrum and related genera supported by four CSPs. We have also identified molecular characteristics that suggest that the polyphyletic order Halobacteriales contains at least two large monophyletic clusters of organisms in addition to the polyphyletic members of the order, one cluster consisting of Haloarcula and related genera supported by ten CSIs and nineteen CSPs and the other group consisting of the members of the genus Halococcus supported by nine CSIs and 23 CSPs. We have also produced a highly robust phylogenetic tree based on the concatenated sequences of 766 proteins which provide additional support for the relationships identified by the CSIs and CSPs. On the basis of the phylogenetic analyses and the identified conserved molecular characteristics presented here, we propose a division of the order Haloferacales into two families, an emended family Haloferacaceae and Halorubraceae fam. nov. and a division of the order Halobacteriales into three families, an emended family Halobacteriaceae, Haloarculaceae fam. nov., and Halococcaceae fam. nov. PMID- 26837780 TI - Fully Ir(iii) tetrazolate soft salts: the road to white-emitting ion pairs. AB - The first examples of anionic Ir(iii) bis-tetrazolate complexes and their combination with a cationic Ir(iii)tetrazole derivative forming "fully tetrazolate" Ir(iii) based soft salts as O2-sensitive white emitters are described herein. PMID- 26837781 TI - Time to insulin initiation and long-term effects of initiating insulin in people with type 2 diabetes mellitus: the Hoorn Diabetes Care System Cohort Study. AB - OBJECTIVE: The aim of this study was to assess the time to insulin initiation in type 2 diabetes mellitus (T2DM) patients treated with oral glucose-lowering agents and to determine the baseline characteristics associated with time to insulin initiation. This was evaluated in T2DM patients with HbA1c levels consistently >=7.0% during total follow up and in those with fluctuating HbA1c levels around 7.0%. DESIGN AND METHODS: Prospective, observational study was performed, comprising 2418 persons with T2DM aged >=40 years who entered the Diabetes Care System between 1998 and 2012 with a minimum follow up of at least 3 years, following the first HbA1c level >=7.0%. Cox regression analyses were performed to assess the determinants of time to insulin initiation. Data related to long-term effects of insulin initiation were studied at baseline and at the end of follow up using descriptive summary statistics. RESULTS: Two-thirds of the patients initiated insulin during follow up. The time to insulin varied from 1.2 years (range 0.3-3.1) in patients with HbA1c levels consistently >=7.0% to 5.4 years (range 3.0-7.5) in patients with fluctuating HbA1c levels around 7.0%. Longer diabetes duration (hazard ratio (HR) 1.04 95% CI 1.03-1.05) and lower age (HR 1.00 95% CI 0.99-1.00) at baseline were associated with a shorter time to initiation. More insulin initiators had retinopathy compared with patients that remained on oral glucose-lowering agents during follow up. CONCLUSION: The time to insulin initiation was short, and most of the patients with HbA1c levels consistently >=7.0% were initiating insulin. Longer diabetes duration and younger age shortened the time to insulin. PMID- 26837782 TI - Long-term outcome after transvaginal mesh repair of pelvic organ prolapse. AB - INTRODUCTION AND HYPOTHESIS: The aim of this study was to report long-term subjective and objective outcomes after the transvaginal mesh (TVM) procedure in long-term. Possible late-onset complications were of particular interest. METHODS: This was a retrospective analysis of TVM performed using ProliftTM transvaginal mesh measuring subjective outcome using validated questionnaires. Objective outcome was assessed using the Pelvic Organ Prolapse Quantification (POP-Q) system using two definitions: POP-Q stage <= 1, and vaginal wall prolapse at or above the hymen or vaginal apex not descending below the upper third of the vagina. Complications were reported with the Prosthesis/Graft Complication Classification Code designed by the International Continence Society/International Urogynecological Association (ICS/IUGA). RESULTS: Of 195 patients, 161 (82.6 %) participated this study after a median of 7 years. The scores in questionnaires evaluating urinary (UI) or anal incontinence and constipation or pelvic floor symptoms were low, indicating favorable surgical outcomes. Altogether, 80.1 % of patients were satisfied with the procedure. Anatomical cure was 56.4 % and 69.3 % depending on the definition used. Reoperation due to POP in any compartment was performed in 16.2 % of patients. Mesh exposure rate was 23 %, most of these being asymptomatic and of late onset. CONCLUSIONS: Outcome of the TVM procedure was satisfactory. Anatomical cure was inferior to subjective cure. Mesh exposure rate was high; most exposures observed in the long-term were of late onset and were asymptomatic. PMID- 26837783 TI - Transperitoneal laparoscopic repair of vesicovaginal fistula for patients with supratrigonal fistula: comparison with open transperitoneal technique. AB - INTRODUCTION AND HYPOTHESIS: We investigated the treatment outcomes of laparoscopic vesicovaginal fistula repair (LVVFR) in patients with supratrigonal vesicovaginal fistula (VVF) in contrast with open transperitoneal vesicovaginal fistula repair (OVVFR). METHODS: We analyzed 58 VVF repairs from June 2005 to July 2014, with 22 patients in the LVVFR group and 36 in the OVVFR group. Demographic parameters, operative variables, and perioperative outcomes were retrospectively collected and analyzed. The chi-square test, Fisher's exact test, Student's t test and the Mann-Whitney U test were used for statistical analysis. RESULTS: Patients in both groups had comparable preoperative characteristics. Significantly shorter hospital stay (5.6 vs. 13.2 days, p < 0.05) and less blood loss (52 vs. 103 ml, p < 0.05) were observed in LVVFR group. Patients in the LVVFR group achieved a higher overall VVF success rate (95.5 % vs. 83.3 %, p > 0.05) and recurrent VVF success rate (90.0 % vs. 75.0 %, p > 0.05) than OVVFR group, but it was not statistically significant. Patients who underwent OVVFR experienced more postoperative symptomatic bladder spasms (8.3 % vs. 4.5 %, p > 0.05), urinary tract infections (UTIs) (5.6 % vs. 0.0 %, p > 0.05), and stress urinary incontinence (SUI) (5.6 % vs. 4.5 %, p > 0.05), but fewer incidents of postoperative ileus (0.0 % vs. 4.5 %, p > 0.05) than the LVVFR group; differences were not significant. CONCLUSIONS: Judging from this initial trial, LVVFR should be recommended as the primary intervention to treat supratrigonal VVF patients in view of its reduced blood loss and hospital stay. PMID- 26837785 TI - The Lichenoid Tissue Reactions of the Oral Mucosa: Oral Lichen Planus and Other Lichenoid Lesions. AB - Lichenoid changes in the oral mucosa can be encountered in a wide range of lesions and can have varied etiologies. Immune-mediated disorders, including lichen planus, mucous membrane pemphigoid, discoid lupus erythematosus, and graft versus-host disease, can have clinical and histologic overlaps. Lichenoid reactions to dental materials, such as amalgam, or to many systemic drugs are also well documented. Dysplasia of the oral cavity at times can also express a lichenoid histology, which may mask the potentially cancerous component. Proliferative verrucous leukoplakia, an unusual clinical disease, mimics oral lichen planus clinically and requires careful correlation of the clinical and pathologic features. PMID- 26837786 TI - Odontogenic Cysts and Tumors. AB - This article presents various odontogenic cysts and tumors, including periapical cysts, dentigerous cysts, odontogenic keratocysts, orthokeratinized odontogenic cysts, lateral periodontal cysts, glandular odontogenic cysts, ameloblastomas, clear cell odontogenic carcinomas, adenomatoid odontogenic tumors, calcifying epithelial odontogenic tumors, squamous odontogenic tumors, ameloblastic fibromas, ameloblastic fibro-odontomas, odontomas, calcifying cystic odontogenic tumors, and odontogenic myxomas. The authors provide an overview of these cysts and tumors, with microsopic features, gross features, differential diagnosis, prognosis, and potential diagnostic pitfalls. PMID- 26837787 TI - Select Neoplasms of the Sinonasal Tract. AB - The sinonasal tract (SNT) includes the nasal cavity and paranasal sinuses (maxillary, ethmoid, frontal, and sphenoid) and may give rise to a variety of nonneoplastic and neoplastic proliferations, including benign and malignant neoplasms. The benign neoplasms of the SNT include epithelial neoplasms of surface epithelial origin, minor salivary gland origin, and mesenchymal origin. The spectrum of malignant neoplasms of the SNT includes epithelial malignancies, sinonasal undifferentiated carcinoma, malignant salivary gland neoplasms, neuroectodermal neoplasms, neuroendocrine neoplasms, melanocytic neoplasm, and sarcomas. This article concentrates on some of the more common types of benign and malignant neoplasms. PMID- 26837784 TI - BDNF contributes to IBS-like colonic hypersensitivity via activating the enteroglia-nerve unit. AB - The over-expressed colonic brain-derived neurotrophic factor (BDNF) has been reported to be associated with abdominal pain in patients with irritable bowel syndrome (IBS). However, the neuropathological mechanism is unclear. We here investigated the involvement of enteroglial cells (EGCs) and enteric nerves in IBS-like visceral hypersensitivity. We showed that glial fibrillary acidic protein (GFAP), tyrosine receptor kinase B (TrkB) and substance P (SP) were significantly increased in the colonic mucosa of IBS patients. The upregulation of those proteins was also observed in the colon of mice with visceral hypersensitivity, but not in the colon of BDNF(+/-) mice. Functionally, TrkB or EGC inhibitors, or BDNF knockdown significantly suppressed visceral hypersensitivity in mice. Using the EGC cell line, we found that recombinant human BDNF (r-HuBDNF) could directly activate EGCs via the TrkB-phospholipase Cgamma1 pathway, thereby inducing a significant upregulation of SP. Moreover, supernatants from r-HuBDNF-activated EGC culture medium, rather than r-HuBDNF alone, triggered markedly augmented discharges in isolated intestinal mesenteric afferent nerves. r-HuBDNF alone could cause mesenteric afferent mechanical hypersensitivity independently, and this effect was synergistically enhanced by activated EGCs. We conclude that EGC-enteric nerve unit may be involved in IBS like visceral hypersensitivity, and this process is likely initiated by BDNF-TrkB pathway activation. PMID- 26837789 TI - Common Lesions of the Larynx and Hypopharynx. AB - Benign and malignant lesions of the larynx and hypopharynx present an interesting and diverse spectrum of diagnostic entities, which may be infrequently encountered in routine surgical pathology practice. This article places emphasis on illustrating the classical pathologic characteristics, differential diagnosis, clinical significance, and presentation of common lesions unique to these sites. The initial diagnosis of these lesions is via small endoscopic biopsy. Many of the entities have overlapping histologic features which necessitate optimizing the information available in a small sample. The focus of this article is to provide useful criteria to enable separating the more common types of lesions encountered in these sites. PMID- 26837788 TI - Squamous Cell Carcinoma of the Oral Cavity and Oropharynx. AB - The most common malignancy to involve the oral cavity and oropharynx is squamous cell carcinoma (SCC). Because these oral cancers share an origin from the squamous epithelium, the pathology of oral SCC might be expected to be uniform and its diagnosis repetitive. In reality, the morphologic diversity in SCC, along with the propensity for reactive processes of the oral cavity to mimic SCC histologically, renders its diagnosis one of the more challenging in surgical pathology. This article discusses variants of oral and oropharyngeal SCC and highlights those features that help distinguish human papillomavirus-related from human papillomavirus-unrelated SCC. PMID- 26837790 TI - Common Malignant Salivary Gland Epithelial Tumors. AB - Malignant salivary gland epithelial tumors are histologically diverse with at least 24 recognized distinct entities. In general, malignant tumors account for 15% to 30% of parotid tumors, 40% to 45% of submandibular tumors, 70% to 90% of sublingual tumors, and 50% of minor salivary tumors. Common malignancies include mucoepidermoid carcinoma, adenoid cystic carcinoma, acinic cell carcinoma, salivary duct carcinoma, carcinoma ex pleomorphic adenoma, polymorphous lowgrade adenocarcinoma, and myoepithelial carcinoma. Each tumor type has its own unique histologic variants and prognostic pathologic features, and only mucoepidermoid carcinomas have a formalized grading system. The molecular pathogenesis of certain tumors, such as mucoepidermoid carcinoma and adenoid cystic carcinoma, has recently begun to be elucidated. PMID- 26837791 TI - Rare Malignant and Benign Salivary Gland Epithelial Tumors. AB - Although at least 24 distinct histologic salivary gland carcinomas exist, many of them are rare, comprising only 1% to 2% of all salivary gland tumors. These include epithelial-myoepithelial carcinoma, (hyalinizing) clear cell carcinoma, basal cell adenocarcinoma, cystadenocarcinoma, low-grade salivary duct carcinoma (low-grade cribriform cystadenocarcinoma), oncocytic carcinoma, and adenocarcinoma not otherwise specified. Few tumors (clear cell carcinoma and basal cell adenocarcinoma) have unique molecular correlates. Benign tumors, although histologically less diverse, are far more common, with pleomorphic adenoma and Warthin tumor the most common salivary gland tumors. Many benign tumors have malignant counterparts for which histologic distinction can pose diagnostic challenge. PMID- 26837792 TI - Bone Lesions of the Head and Neck. AB - This article describes the clinical, radiographic, and pathologic features of tumors and tumorlike lesions affecting the bones of the head and neck region. Emphasis is placed on common bone lesions affecting the craniofacial skeleton, particularly those that occur with more frequency or those that are unique to this part of the skeleton. Several of these lesions pose a diagnostic challenge to the pathologist. To ensure that a correct diagnosis is rendered, it is of utmost importance that accurate and detailed clinical and radiographic information is available. PMID- 26837793 TI - Are There Challenges in the Interpretation of Head and Neck Specimens? PMID- 26837794 TI - Fluorine-Free Superhydrophobic Coatings with pH-induced Wettability Transition for Controllable Oil-Water Separation. AB - We present a simple, environmentally friendly approach to fabricating superhydrophobic coatings with pH-induced wettability transition. The coatings are prepared from a mixture of silica nanoparticles and decanoic acid-modified TiO2. When the coating is applied on cotton fabric, the fabric turns superhydrophobic in air but superoleophilic in neutral aqueous environment. It is permeable to oil fluids but impermeable to water. However, when the coated fabric is placed in basic aqueous solution or ammonia vapor, it turns hydrophilic but underwater superoleophobic, thus allowing water to penetrate through but blocking oil. Therefore, such a unique, selective water/oil permeation feature makes the treated fabric have capability to separate either oil or water from a water-oil mixture. It may be useful for development of smart oil-water separators, microfluidic valves, and lab-on-a-chip devices. PMID- 26837796 TI - A decade of pharmacogenomics research on tyrosine kinase inhibitors in metastatic renal cell cancer: a systematic review. AB - OBJECTIVE: The individual response to targeted tyrosine kinase inhibitors (TKIs) in the treatment of metastatic renal cell cancer (mRCC) is highly variable. Outlined in this article are findings on potential biomarkers for TKI treatment outcome in mRCC and an evaluation of the status of clinical implementation. METHODS: Articles were selected by two independent reviewers using a systematic search in five medical databases on renal cell carcinoma, TKIs, and pharmacogenetics. RESULTS: Many researchers have focused on predictive biomarkers for treatment outcome of targeted therapies in mRCC patients. Attempts to explain differences in efficacy and toxicity of TKIs by use of genetic variants in genes related to the pharmacokinetics and pharmacodynamics of the drug have been successful. CONCLUSION: Most findings on potential biomarkers have not been validated and therefore biomarker testing to guide choice of therapy and dose in mRCC is not yet feasible. PMID- 26837797 TI - Diversity of Mycotoxin-Producing Black Aspergilli in Canadian Vineyards. AB - Several Aspergillus species produce ochratoxin A (OTA) and/or fumonisins on wine and table grapes. The relevant species and their mycotoxins have been investigated in a number of wine-producing regions around the world; however, similar data have not been reported for Canadian vineyards. A multiyear survey of black Aspergilli in Niagara, ON, vineyards was conducted to determine the diversity of species present and to assess the risk of OTA and fumonisin contamination of wine grapes from this region. From 2012 to 2014, 253 black Aspergilli were isolated from soil samples and the fruits of 10 varieties of grapes. The isolates were identified by DNA sequencing: Aspergillus welwitschiae (43%), Aspergillus uvarum (32%), Aspergillus brasiliensis (11%), Aspergillus tubingensis (9%), and Aspergillus niger (4%). Aspergillus carbonarius, the primary OTA producer on grapes in other parts of the world, was isolated only once, and this is the first report for it in Canada. All 10 A. niger strains produced fumonisins, but, in contrast, only 26% of the 109 A. welwitschiae isolates were producers, and no strains of either species produced OTA. Grape samples were analyzed for OTA and fumonisins from sites where strains with mycotoxigenic potential were isolated. Fumonisin B2 (FB2) was detected in 7 of 22 (32%) of these grape samples in the 1-15 ppb range, but no OTA was detected. Additionally, the recently reported nonaminated fumonisins were detected in 3 of 22 grape samples. These results suggest that fumonisin-producing Aspergilli can occur in Ontario vineyards but, at present, the risk of contamination of grapes appears low. The risk of OTA contamination in Niagara wine is also low because of the low prevalence of A. carbonarius. PMID- 26837798 TI - Elastic cavitation and fracture via injection. AB - The cavitation rheology technique extracts soft materials mechanical properties through pressure-monitored fluid injection. Properties are calculated from the system's response at a critical pressure that is governed by either elasticity or fracture (or both); however previous elementary analysis has not been capable of accurately determining which mechanism is dominant. We combine analyses of both mechanisms in order to determine how the full system thermodynamics, including far-field compliance, dictate whether a bubble in an elastomeric solid will grow through either reversible or irreversible deformations. Applying these analyses to experimental data, we demonstrate the sensitivity of cavitation rheology to microstructural variation via a co-dependence between modulus and fracture energy. PMID- 26837799 TI - Biokinetics of ultrafine gold nanoparticles (AuNPs) relating to redistribution and urinary excretion: a long-term in vivo study. AB - Gold nanoparticles (AuNPs) of ultrafine size have drawn attention for their use in drug delivery systems. Tissue toxicity may be an issue when AuNPs are used for such applications. We investigated the long-term biokinetics (90 d), redistribution, and urinary excretion of three different-sized (2 +/- 0.5 nm, 5 +/- 1 nm, and 10 +/- 2 nm) AuNPs after a single intravenous (i.v.) administration of 1250 ug/kg dose in mice. ICP-AES analysis of lungs, liver, spleen, heart, kidney, brain, blood, and urine revealed highest accumulation of gold in spleen around 15 d after injection. A low concentration was detected in brain after 1 d without any residual AuNPs after 30 d. Ultrastructural study of brain tissue also showed few AuNPs in lysosome with no changes in cellular architecture. Renal retention of AuNPs was limited indicating low nephrotoxic potential. AuNPs were detectable in urine till 30 d after single injection indicating slow excretion from the body. No evidence of significant toxicity was observed in hemogram, serum biochemistry, and tissue histology. No mortality, changes in behavior, hair color, weight, and food intake was observed as compared to control mice. Therefore, we conclude that the ultrafine AuNPs are predominantly excreted in urine without any systemic toxicity following i.v. administration and are hence safe for use in drug delivery systems. PMID- 26837800 TI - Competence feedback improves CBT competence in trainee therapists: A randomized controlled pilot study. AB - OBJECTIVE: The development and improvement of therapeutic competencies are central aims in psychotherapy training; however, little is known about which training interventions are suitable for the improvement of competencies. METHOD: In the current pilot study, the efficacy of feedback regarding therapeutic competencies was investigated in cognitive behavioural therapy (CBT). Totally 19 trainee therapists and 19 patients were allocated randomly to a competence feedback group (CFG) or control group (CG). Two experienced clinicians and feedback providers who were blind to the treatment conditions independently evaluated therapeutic competencies on the Cognitive Therapy Scale at five treatment times (i.e., at Sessions 1, 5, 9, 13, and 17). Whereas CFG and CG included regular supervision, only therapists in the CFG additionally received written qualitative and quantitative feedback regarding their demonstrated competencies in conducting CBT during treatment. RESULTS: We found a significant Time * Group interaction effect (eta2 = .09), which indicates a larger competence increase in the CFG in comparison to the CG. CONCLUSIONS: Competence feedback was demonstrated to be suitable for the improvement of therapeutic competencies in CBT. These findings may have important implications for psychotherapy training, clinical practice, and psychotherapy research. However, further research is necessary to ensure the replicability and generalizability of the findings. PMID- 26837801 TI - Efficient, flexible and mechanically robust perovskite solar cells on inverted nanocone plastic substrates. AB - Utilization of nanostructures on photovoltaic devices can significantly improve the device energy conversion efficiency by enhancing the device light harvesting capability as well as carrier collection efficiency. However, improvements in device mechanical robustness and reliability, particularly for flexible devices, have rarely been reported with in-depth understanding. In this work, we fabricated efficient, flexible and mechanically robust organometallic perovskite solar cells on plastic substrates with inverted nanocone (i-cone) structures. Compared with the reference cell that was fabricated on a flat substrate, it was shown that the device power conversion efficiency could be improved by 37%, and reached up to 11.29% on i-cone substrates. More interestingly, it was discovered that the performance of an i-cone device remained more than 90% of the initial value even after 200 mechanical bending cycles, which is remarkably better than for the flat reference device, which degraded down to only 60% in the same test. Our experiments, coupled with mechanical simulation, demonstrated that a nanostructured template can greatly help in relaxing stress and strain upon device bending, which suppresses crack nucleation in different layers of a perovskite solar cell. This essentially leads to much improved device reliability and robustness and will have significant impact on practical applications. PMID- 26837802 TI - Scalable graphene production: perspectives and challenges of plasma applications. AB - Graphene, a newly discovered and extensively investigated material, has many unique and extraordinary properties which promise major technological advances in fields ranging from electronics to mechanical engineering and food production. Unfortunately, complex techniques and high production costs hinder commonplace applications. Scaling of existing graphene production techniques to the industrial level without compromising its properties is a current challenge. This article focuses on the perspectives and challenges of scalability, equipment, and technological perspectives of the plasma-based techniques which offer many unique possibilities for the synthesis of graphene and graphene-containing products. The plasma-based processes are amenable for scaling and could also be useful to enhance the controllability of the conventional chemical vapour deposition method and some other techniques, and to ensure a good quality of the produced graphene. We examine the unique features of the plasma-enhanced graphene production approaches, including the techniques based on inductively-coupled and arc discharges, in the context of their potential scaling to mass production following the generic scaling approaches applicable to the existing processes and systems. This work analyses a large amount of the recent literature on graphene production by various techniques and summarizes the results in a tabular form to provide a simple and convenient comparison of several available techniques. Our analysis reveals a significant potential of scalability for plasma-based technologies, based on the scaling-related process characteristics. Among other processes, a greater yield of 1 g * h(-1) m(-2) was reached for the arc discharge technology, whereas the other plasma-based techniques show process yields comparable to the neutral-gas based methods. Selected plasma-based techniques show lower energy consumption than in thermal CVD processes, and the ability to produce graphene flakes of various sizes reaching hundreds of square millimetres, and the thickness varying from a monolayer to 10-20 layers. Additional factors such as electrical voltage and current, not available in thermal CVD processes could potentially lead to better scalability, flexibility and control of the plasma-based processes. Advantages and disadvantages of various systems are also considered. PMID- 26837803 TI - UNDERSTANDING VARIATIONS IN RELATIVE EFFECTIVENESS: A HEALTH PRODUCTION APPROACH. AB - BACKGROUND: Relative effectiveness has become a key concern of health policy. In Europe, this is because of the need for early information to guide reimbursement and funding decisions about new medical technologies. However, ways that effectiveness (does it work?) and efficacy (can it work?) might differ across health systems are poorly understood. METHODS: This study proposes an analytical framework, drawing on production function theory, to systematically identify and quantify the determinants of relative effectiveness and sources of variation between populations and healthcare systems. We consider how methods such as stochastic frontier analysis and data envelopment analysis using a Malmquist productivity index could in principle be used to generate evidence on, and improve understanding about, the sources of variation in relative effectiveness between countries and over time. RESULTS: Better evidence on factors driving relative effectiveness could: inform decisions on how to best use a new technology to maximum effectiveness; establish the need if any for follow-up post launch studies, and provide evidence of the impact of new health technologies on outcomes in different healthcare systems. CONCLUSIONS: The health production function approach for assessment of relative effectiveness is complementary to traditional experimental and observational studies, focusing on identifying, collecting, and analyzing data at the national level, enabling comparisons to take place. There is a strong case for exploring the use of this approach to better understand the impact of new medicines and devices for improvements in health outcomes. PMID- 26837804 TI - Molecular Modeling of the Structural and Dynamical Changes in Calcium Channel TRPV5 Induced by the African-Specific A563T Variation. AB - Transient receptor potential cation channels, vanilloid subfamily, member 5 (TRPV5) plays a key role in active Ca(2+) reabsorption in the kidney. Variations in TRPV5 occur at high frequency in African populations and may contribute to their higher efficiency of Ca(2+) reabsorption. One of the African specific variations, A563T, exhibits increased Ca(2+) transport ability. However, it is unclear how this variation influences the channel pore. On the basis of the structure of TRPV1, a TRPV5 model was generated to simulate the structural and dynamical changes induced by the A563T variation. On the basis of this model, amino acid residue 563 interacts with V540, which is one residue away from the key residue, D542, involved in Ca(2+) selectivity and Mg(2+) blockade. The A563T variation increases secondary structure stability and reduces dynamical motion of D542. In addition, the A563T variation alters the electrostatic potential of the outer surface of the pore. Differences in contact between selective filter residues and residue 563 and in electrostatic potential between the two TRPV5 variants were also observed in another model derived from an alternative alignment in the selective filters between TRPV5 and TRPV1. These findings indicate that the A563T variation induces structural, dynamical, and electrostatic changes in the TRPV5 pore, providing structural insight into the functional alterations associated with the A563T variation. PMID- 26837806 TI - Price JS, Tackett S, Patel V. Observational evaluation of outcomes and resource utilization from hemostatic matrices in spine surgery. J Med Econ 2015; 1-10. PMID- 26837805 TI - Cyclic pi-electron delocalization in non-planar linear acenes. AB - Based on the experimental data of newly determined structures of per-substituted naphthalenes by halogen atoms (F, Cl and Br) and perchloroanthracene, as well as on the molecular modeling we have shown that deviation from planarity leads to relatively small changes in the cyclic pi-electron delocalization of acenes. Per substituted naphthalenes are twisted, whereas perchloroanthracene adopts a boat conformation in the solid state. For the most distorted case - perbromonaphthalene twisted by 34.7 degrees , the geometry-based HOMA index drops down by 0.128 of the unit only, which means ca. 15% reduction of the extent of pi electron delocalization as referred to naphthalene. To account for the changes in the aromatic stabilization energies (ASEs), exaltation of magnetic susceptibilities (Lambda) and strain energies (SEs) upon bending we have proposed a set of homodesmotic reactions based on the peri-substituted systems, where the reference compounds have similar conformation to the distorted aromatics. The decrease of aromaticity is smooth, but regular in a rather large range of distortion. Notably, the most extreme case - 1,4,5,8-tetra-t-butylnaphthalene, twisted by 51.7 degrees with an estimated strain energy of 26 kcal mol(-1) - is still aromatic. The ASE, Lambda and HOMA decrease by 19.1 kcal mol(-1), 7 cgs-ppm and 0.34 of the unit, respectively, as referred to naphthalene. PMID- 26837807 TI - Mitochondrial impairment induced by postnatal ActRIIB blockade does not alter function and energy status in exercising mouse glycolytic muscle in vivo. AB - Because it leads to a rapid and massive muscle hypertrophy, postnatal blockade of the activin type IIB receptor (ActRIIB) is a promising therapeutic strategy for counteracting muscle wasting. However, the functional consequences remain very poorly documented in vivo. Here, we have investigated the impact of 8-wk ActRIIB blockade with soluble receptor (sActRIIB-Fc) on gastrocnemius muscle anatomy, energy metabolism, and force-generating capacity in wild-type mice, using totally noninvasive magnetic resonance imaging (MRI) and dynamic(31)P-MRS. Compared with vehicle (PBS) control, sActRIIB-Fc treatment resulted in a dramatic increase in body weight (+29%) and muscle volume (+58%) calculated from hindlimb MR imaging, but did not alter fiber type distribution determined via myosin heavy chain isoform analysis. In resting muscle, sActRIIB-Fc treatment induced acidosis and PCr depletion, thereby suggesting reduced tissue oxygenation. During an in vivo fatiguing exercise (6-min repeated maximal isometric contraction electrically induced at 1.7 Hz), maximal and total absolute forces were larger in sActRIIB-Fc treated animals (+26 and +12%, respectively), whereas specific force and fatigue resistance were lower (-30 and -37%, respectively). Treatment with sActRIIB-Fc further decreased the maximal rate of oxidative ATP synthesis (-42%) and the oxidative capacity (-34%), but did not alter the bioenergetics status in contracting muscle. Our findings demonstrate in vivo that sActRIIB-Fc treatment increases absolute force-generating capacity and reduces mitochondrial function in glycolytic gastrocnemius muscle, but this reduction does not compromise energy status during sustained activity. Overall, these data support the clinical interest of postnatal ActRIIB blockade. PMID- 26837809 TI - Regulation of metabolism: the work-to-rest transition in skeletal muscle. AB - The behavior of oxidative phosphorylation predicted by a model for the mechanism and kinetics of cytochrome c oxidase is compared with the experimentally observed behavior during the work-to-rest transition in skeletal muscle. For both experiment and model, when work stops, the increase in creatine phosphate and decrease in creatine and inorganic phosphate concentrations ([CrP], [Cr], and [Pi]) begin immediately. The rate of change for each is maximal and then progressively slows as the increasing energy state ([ATP]/[ADP][Pi]) suppresses the rate of oxidative phosphorylation. The time courses can be reasonably fitted to single exponential curves with similar time constants. The energy state in the working and resting steady states at constant Po2 are dependent on the intramitochondrial [NAD+]/[NADH], mitochondrial content, and size of the creatine pool ([CrP] + [Cr]). The rate of change in [CrP] is linearly correlated with [CrP] and with [Pi] and [Cr]. The time constant for [CrP] increase in the resting and working steady states, and the rate of decrease in oxygen consumption are similarly dependent on the Po2 in the inspired gas (experimental) or tissue Po2 (model). Myoglobin strongly buffers intracellular Po2 below ~15 torr, truncating the low end of the oxygen distribution in the tissue and suppressing intra- and intermyocyte oxygen gradients. The predictions of the model are consistent with the experimental data throughout the work/rest transition, providing valuable insights into the regulation of cellular and tissue metabolism. PMID- 26837810 TI - Temperature Changes Inside the Kidney: What Happens During Holmium:Yttrium Aluminium-Garnet Laser Usage? AB - INTRODUCTION: The improvements in flexible ureteroscopes provide efficient access to the upper urinary tract and advancements in laser technology strengthens the endourologists' armamentarium. The endourologists must be aware of the advantages and the potential complications of these powerful technological equipments. Our aim is to demonstrate temperature evolution during laser use inside an artificial kidney model. MATERIALS AND METHODS: We created a bench model using K-Box((r)) immersed into a saline-filled heating tank, which was used to obtain the needed temperature inside the cavity to provide different real-time situations. An endotracheal thermometer was placed inside. We used Olympus URF-P6 ureteroscope and Rocamed Holmium:yttrium-aluminium-garnet laser with two different fibers; 200 and 272 MUm, at five different settings. Irrigation at room (24.5 degrees C) and body (36.5 degrees C) temperatures was used. We measured temperatures at 15th, 30th, and 45th seconds and 1st, 2nd, and 5th minutes of laser use with and without irrigation. We stopped measurements when temperature reached the upper limit of the endotracheal thermometer. RESULTS: When irrigation was closed, with 272-MUm laser fiber, we reached the temperature limit more rapidly with saline tank at 36.5 degrees C than the tank at 24.5 degrees C. When irrigation was closed, with both fibers and regardless of tank temperature and laser settings, the system surpassed the maximum temperature limit. With 272-MUm laser fiber, the limit was reached as early as the 30th second. When the irrigation was open, we did not reach the maximum temperature limit regardless of tank temperature and laser setting. When two laser fibers were compared, the temperature increase was more pronounced with 272-MUm fiber, but the difference was not statistically significant. CONCLUSION: Laser use during flexible ureteroscopy may cause increased intrarenal temperatures. Rapid increases should be kept in mind when irrigation is closed. The irrigation seems to limit the temperature increase when used with any laser setting. PMID- 26837808 TI - Paracrine regulation of glucagon secretion: the beta/alpha/delta model. AB - The regulation of glucagon secretion in the pancreatic alpha-cell is not well understood. It has been proposed that glucose suppresses glucagon secretion either directly through an intrinsic mechanism within the alpha-cell or indirectly through an extrinsic mechanism. Previously, we described a mathematical model for isolated pancreatic alpha-cells and used it to investigate possible intrinsic mechanisms of regulating glucagon secretion. We demonstrated that glucose can suppress glucagon secretion through both ATP-dependent potassium channels (KATP) and a store-operated current (SOC). We have now developed an islet model that combines previously published mathematical models of alpha- and beta-cells with a new model of delta-cells and use it to explore the effects of insulin and somatostatin on glucagon secretion. We show that the model can reproduce experimental observations that the inhibitory effect of glucose remains even when paracrine modulators are no longer acting on the alpha-cell. We demonstrate how paracrine interactions can either synchronize alpha- and delta cells to produce pulsatile oscillations in glucagon and somatostatin secretion or fail to do so. The model can also account for the paradoxical observation that glucagon can be out of phase with insulin, whereas alpha-cell calcium is in phase with insulin. We conclude that both paracrine interactions and the alpha-cell's intrinsic mechanisms are needed to explain the response of glucagon secretion to glucose. PMID- 26837811 TI - Simultaneous inclusion of sorghum and cottonseed meal or millet in broiler diets: effects on performance and nutrient digestibility. AB - Two experiments were conducted to investigate the use of sorghum, cottonseed meal and millet in broiler diets and their interaction when they are used simultaneously. In Experiment 1, a corn-soybean meal control diet was compared with eight experimental treatments based on low tannin sorghum (S30, S45 and S60), cottonseed meal (CM15, CM40) or both ingredients included in the same diet (S30/CM40, S45/CM25 and S60CM15). Results showed that BW gain was not affected by the inclusion of sorghum or cottonseed meal. However, feed intake tended to be affected by the cereal type with the highest values with sorghum-based diets. Feed conversion ratio increased (P<0.001) with sorghum-based diets compared with the control diet, whereas a combination of cottonseed meal and sorghum in the same diet did not affect the feed conversion ratio. Significant differences (P<0.001) were observed in apparent ileal digestibility (%) of protein and energy with the cottonseed meal and sorghum/cottonseed meal-based diets having lower protein and energy digestibility compared with corn-based diets. In Experiment 2, a control diet was compared with six diets in which corn was substituted at 60%, 80% or 100% by either sorghum or millet and other three diets with simultaneous inclusion of these two ingredients (S30/M30, S40/M40, S50/M50). Single or combined inclusion of sorghum and millet resulted in similar feed intake and growth performance as the control diet. Apparent ileal digestibility of protein and energy was higher with millet-based diets (P<0.001). Total tract digestibility of protein in sorghum and millet-based diets tended to decrease linearly with the increasing level of substitution. Sorghum-based diets resulted in lower total tract digestibility of fat compared with millet and sorghum/millet based diets (P<0.001). Higher total tract digestibility of starch were obtained with the control diet and millet-based diets compared with the sorghum-based treatments. Results of the two experiments suggest that broiler growth performance was not affected by the dietary level of sorghum, millet or cottonseed meal. Nutrient digestion can, however, be affected by these feed ingredients. PMID- 26837812 TI - Development and usability of the MAINtAIN, an inventory assessing nursing staff behavior to optimize and maintain functional activity among nursing home residents: a mixed-methods approach. AB - BACKGROUND: Functional decline is common in nursing home residents. Nursing staff can help prevent this decline, by encouraging residents to be more active in functional activities. Questionnaires measuring the extent to which nursing staff encourage functional activity among residents are lacking. In addition, there are no measurement instruments to gain insight into nursing staff perceived barriers and facilitators to this behavior. The aim of this study was to develop, and study the usability, of the MAastrIcht Nurses Activities INventory (MAINtAIN), an inventory assessing a) the extent to which nursing staff perceive to perform behaviors that optimize and maintain functional activity among nursing home residents and b) the perceived barriers and facilitators related to this behavior. METHODS: Using a mixed-methods approach the MAINtAIN was developed and its usability was studied. Development was based on literature, expert opinions, focus group (N = 3) and individual interviews (N = 14) with residents and staff from nine nursing homes in the Netherlands. Usability was studied in a cross sectional study with 37 nurses and certified nurse assistants; data were analyzed using descriptive statistics. RESULTS: Development of the MAINtAIN resulted in two distinctive parts: MAINtAIN-behaviors and MAINtAIN-barriers. MAINtAIN behaviors, targeting nursing staff behavior to optimize and maintain functional activity, includes 19 items covering activities of daily living, household activities, and miscellaneous activities. MAINtAIN-barriers addresses the perceived barriers and facilitators related to this behavior and comprises 33 items covering barriers and facilitators related to the residents, the professionals, the social context, and the organizational and economic context. The usability study showed that the inventory was not difficult to complete, that items and response options were clear, and that the number of missing values was low. Few items showed a floor or ceiling effect. CONCLUSIONS: The newly developed inventory MAINtAIN provides a usable method for researchers and nursing homes to obtain insight into nursing staff perceived behavior in optimizing functional activity among residents and their perceived barriers and facilitators related to this behavior. Outcomes of the MAINtAIN may contribute to change in nursing staff behavior and may improve nursing care. Further research with regard to the psychometric properties of the MAINtAIN is recommended. PMID- 26837814 TI - Specific renal parenchymal-derived urinary extracellular vesicles identify age associated structural changes in living donor kidneys. AB - Non-invasive tests to identify age and early disease-associated pathology within the kidney are needed. Specific populations of urinary extracellular vesicles (EVs) could potentially be used for such a diagnostic test. Random urine samples were obtained from age- and sex-stratified living kidney donors before kidney donation. A biopsy of the donor kidney was obtained at the time of transplantation to identify nephron hypertrophy (larger glomerular volume, cortex per glomerulus and mean profile tubular area) and nephrosclerosis (% fibrosis, % glomerulosclerosis and arteriosclerosis). Renal parenchymal-derived EVs in cell free urine were quantified by digital flow cytometry. The relationship between these EV populations and structural pathology on the kidney biopsy was assessed. Clinical characteristics of the kidney donors (n=138, age range: 20-70 years, 50% women) were within the normative range. Overall, urine from women contained more EVs than that from men. The number of exosomes, juxtaglomerular cells and podocyte marker-positive EVs decreased (p<0.05) with increasing age. There were fewer total EVs as well as EVs positive for mesangial cell, parietal cell, descending limb of Henle's loop (simple squamous epithelium), collecting tubule intercalated cell and monocyte chemoattractant protein-1 markers (p<0.05) in persons with nephron hypertrophy. The number of EVs positive for intercellular adhesion molecule-1, juxtaglomerular cell, podocyte, parietal cell, proximal tubular epithelial cell, distal tubular epithelial cell and collecting duct cells were fewer (p<0.05) in persons with nephrosclerosis. EVs carrying markers of cells from the renal pelvis epithelium did not associate with any indices of nephron hypertrophy or nephrosclerosis. Therefore, specific populations of EVs derived from cells of the glomerulus and nephron associate with underlying kidney structural changes. Further validation of these findings in other cohorts is needed to determine their clinical utility. PMID- 26837815 TI - 'God grant it may do good two all': the madhouse practice of Joseph Mason, 1738 79. AB - Private madhouses made a significant contribution to the development of psychiatric practices in eighteenth-century England. Joseph Mason of Bristol, proprietor of a madhouse at Stapleton and then at nearby Fishponds, was part of a dynasty of successful and respected mad-doctors. A deeply religious man, his Christian ethics constituted the guiding force in his work with patients and interactions with their relatives. He was also an astute man of business, who recognized that comfortable domestic surroundings and the achievement of recoveries would enhance his reputation and attract lucrative middle-class custom. His treatment approaches, illustrated in a 1763 diary, were eclectic and pragmatic, comprising various medicines, dietary regulation, graded social interactions, and the cultivation of individualized therapeutic relationships with his patients. PMID- 26837813 TI - Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study. AB - OBJECTIVE: To determine whether higher cumulative use of benzodiazepines is associated with a higher risk of dementia or more rapid cognitive decline. DESIGN: Prospective population based cohort. SETTING: Integrated healthcare delivery system, Seattle, Washington. PARTICIPANTS: 3434 participants aged >= 65 without dementia at study entry. There were two rounds of recruitment (1994-96 and 2000-03) followed by continuous enrollment beginning in 2004. MAIN OUTCOMES MEASURES: The cognitive abilities screening instrument (CASI) was administered every two years to screen for dementia and was used to examine cognitive trajectory. Incident dementia and Alzheimer's disease were determined with standard diagnostic criteria. Benzodiazepine exposure was defined from computerized pharmacy data and consisted of the total standardized daily doses (TSDDs) dispensed over a 10 year period (a rolling window that moved forward in time during follow-up). The most recent year was excluded because of possible use for prodromal symptoms. Multivariable Cox proportional hazard models were used to examine time varying use of benzodiazepine and dementia risk. Analyses of cognitive trajectory used linear regression models with generalized estimating equations. RESULTS: Over a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia, of whom 637 developed Alzheimer's disease. For dementia, the adjusted hazard ratios associated with cumulative benzodiazepine use compared with non-use were 1.25 (95% confidence interval 1.03 to 1.51) for 1-30 TSDDs; 1.31 (1.00 to 1.71) for 31-120 TSDDs; and 1.07 (0.82 to 1.39) for >= 121 TSDDs. Results were similar for Alzheimer's disease. Higher benzodiazepine use was not associated with more rapid cognitive decline. CONCLUSION: The risk of dementia is slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. These results do not support a causal association between benzodiazepine use and dementia. PMID- 26837816 TI - Association of TNF-alpha genetic polymorphisms with recurrent pregnancy loss risk: a systematic review and meta-analysis. AB - BACKGROUND: Several studies on the association of tumor necrosis factor alpha (TNF-alpha) polymorphisms with recurrent pregnancy loss (RPL) risk have reported conflicting results. The present meta-analysis was conducted to provide a more precise estimation of these relationships and to investigate the real association between TNF-alpha polymorphisms and RPL. METHODS: An extensive eligible literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library from their inceptions to May 12, 2015. Specific inclusion criteria were used to evaluate articles. The odds ratio (OR) with 95% confidence intervals (CIs) were used to assess the strength of associations. Statistical analyses were performed by the STATA12.0 software. RESULTS: 10 case-control studies including 1430 RPL patients and 1727 healthy controls were identified. Meta-analysis indicated that TNF-alpha-308G/A (rs1800629) polymorphism in the TNF alpha gene correlated with elevated RPL risk whereas no significant association was observed between TNF-alpha-238G/A (rs361625) and RPL. CONCLUSIONS: The current meta-analysis demonstrates that TNF-alpha-308G/A polymorphism in the TNF alpha gene is associated with susceptibility to RPL. PMID- 26837817 TI - A cluster-randomised controlled trial of values-based training to promote autonomously held recovery values in mental health workers. AB - BACKGROUND: The implementation and use of evidence-based practices is a key priority for recovery-oriented mental health service provision. Training and development programmes for employees continue to be a key method of knowledge and skill development, despite acknowledged difficulties with uptake and maintenance of behaviour change. Self-determination theory suggests that autonomy, or a sense that behaviour is self-generated, is a key motivator to sustained behaviour change, in this case practices in mental health services. This study examined the utility of values-focused staff intervention as a specific, reproducible method of autonomy support. METHODS: Mental health workers (n = 146) were assigned via cluster randomisation to either a values clarification condition or an active problem-solving control condition. RESULTS: Results demonstrated that a structured values clarification exercise was useful in promoting integrated motivation for the changed practice and resulted in increased implementation planning. CONCLUSIONS: Structured values clarification intervention demonstrates utility as a reproducible means of autonomy support within the workplace. We discuss future directions for the study of autonomous motivation in the field of implementation science. TRIAL REGISTRATION: ACTRN12613000353796. PMID- 26837821 TI - Two new phragmalin-type limonoids from Chukrasia tabularis and their alpha glucosidase inhibitory activity. AB - Phytochemical investigation on the stems of C. tabularis (Meliaceae) led to the isolation of two new phragmalin-type limonoids, named tabularisins S and T (1-2), along with five known ones (3-7). The structures of the new limonoids were established by spectroscopic methods including UV, IR, HRESIMS, and 1D and 2D NMR. All the compounds were evaluated for alpha-glucosidase inhibitory activity in vitro. Compounds 2 and 3 exhibited significant inhibitory activity against alpha-glucosidase with IC50 values of 0.15 and 0.03 mM, respectively (acarbose as positive control, IC50 0.95 mM). PMID- 26837822 TI - Should adrenaline be used in patients with hemodynamically stable anaphylaxis? Incident case control study nested within a retrospective cohort study. AB - Although adrenaline (epinephrine) is a cornerstone of initial anaphylaxis treatment, it is not often used. We sought to assess whether use of adrenaline in hemodynamically stable patients with anaphylaxis could prevent the development of hypotension. We conducted a retrospective cohort study of 761 adult patients with anaphylaxis presenting to the emergency department (ED) of a tertiary care hospital over a 10-year period. We divided the patients into two groups according to the occurrence of hypotension and compared demographic characteristics, clinical features, treatments and outcomes. Of the 340 patients with anaphylaxis who were normotensive at first presentation, 40 patients experienced hypotension during their ED stay. The ED stay of the hypotension group was significantly longer than that of patients who did not experience hypotension (496 min vs 253 min, P = 0.000). Adrenaline use in hemodynamically stable anaphylaxis patient was independently associated with a lower risk of developing in-hospital occurrence of hypotension: OR, 0.254 [95% CI, 0.091-0.706]. Adrenaline use in hemodynamically stable anaphylaxis patients was associated with a reduced risk of developing in-hospital occurrence of hypotension. Adverse events induced by adrenaline were rare when the intramuscular route was used. PMID- 26837823 TI - Electronic Spectra of Protonated Fluoranthene in a Neon Matrix and Gas Phase at 10 K. AB - Four electronic systems with origin bands at 759.5, 559.3, 476.3, and 385.5 nm are detected in a 6 K neon matrix following deposition of mass-selected protonated fluoranthene C16H11(+) produced from a reaction of neutral vapor and ethanol in a hot-cathode ion source. Two cationic isomers are identified as the carriers of these band systems. The 559.3, 476.3, and 385.5 nm absorptions are assigned to 4,3,2 (1)A' <- X (1)A' transitions of isomer E(+) (gamma-) and the 2 (1)A' <- X (1)A' system at 759.5 nm is of isomer C(+) (alpha-) of protonated fluoranthene on the basis of theoretical predictions. The electronic spectrum of E(+) was also recorded in the gas phase using a resonant 1 + 1 two-photon excitation-dissociation technique in an ion trap at vibrational and rotational temperatures of 10 K. The 3,2 (1)A' <- X (1)A' transitions have origin band maxima at 558.28 +/- 0.01 and 474.92 +/- 0.01 nm. Both the 2 (1)A' and 3 (1)A' excited states have a distinct vibrational pattern with lifetimes on the order of 1 ps. PMID- 26837825 TI - Removal of Cryptosporidium by wastewater treatment processes: a review. AB - Cryptosporidium is a protozoan parasite that infects humans and various animal species. The environmental stability and the low infectious dose of Cryptosporidium facilitate its transmission by water and food. Discharge of untreated wastewater may result in waterborne or foodborne Cryptosporidium outbreaks, therefore a suitable treatment may prevent its dissemination. Most studies on the prevalence of Cryptosporidium oocysts in wastewater have reported a concentration range between 10 and 200 oocysts/L and a prevalence of 6 to 100%. Activated sludge has been found to be ineffective for the removal of Cryptosporidium oocysts. Stabilization ponds and constructed wetlands are efficient for the reduction of Cryptosporidium from wastewater, especially when the retention time is longer than 20 days at suitable sunlight and temperature. High rate filtration and chlorine disinfection are inefficient for the reduction of Cryptosporidium from effluents, whereas ultrafiltration and UV irradiation were found to be very efficient for the reduction of Cryptosporidium oocysts. Adequate tertiary treatment may result in high quality effluent with low risk of Cryptosporidium for unrestricted irrigation and other non-potable applications. PMID- 26837824 TI - Major bacterial lineages are essentially devoid of CRISPR-Cas viral defence systems. AB - Current understanding of microorganism-virus interactions, which shape the evolution and functioning of Earth's ecosystems, is based primarily on cultivated organisms. Here we investigate thousands of viral and microbial genomes recovered using a cultivation-independent approach to study the frequency, variety and taxonomic distribution of viral defence mechanisms. CRISPR-Cas systems that confer microorganisms with immunity to viruses are present in only 10% of 1,724 sampled microorganisms, compared with previous reports of 40% occurrence in bacteria and 81% in archaea. We attribute this large difference to the lack of CRISPR-Cas systems across major bacterial lineages that have no cultivated representatives. We correlate absence of CRISPR-Cas with lack of nucleotide biosynthesis capacity and a symbiotic lifestyle. Restriction systems are well represented in these lineages and might provide both non-specific viral defence and access to nucleotides. PMID- 26837826 TI - Estimation of concentration ratio of indicator to pathogen-related gene in environmental water based on left-censored data. AB - A stochastic model for estimating the ratio between a fecal indicator and a pathogen based on left-censored data, which includes a substantially high number of non-detects, was constructed. River water samples were taken for 16 months at six points in a river watershed, and conventional fecal indicators (total coliforms and general Escherichia coli), genetic markers (Bacteroides spp.), and virulence genes (eaeA of enteropathogenic E. coli and ciaB of Campylobacter jejuni) were quantified. The quantification of general E. coli failed to predict the presence of the virulence gene from enteropathogenic E. coli, different from what happened with genetic markers (Total Bac and Human Bac). A Bayesian model that was adapted to left-censored data with a varying analytical quantification limit was applied to the quantitative data, and the posterior predictive distributions of the concentration ratio were predicted. When the sample size was 144, simulations conducted in this study suggested that 39 detects were enough to accurately estimate the distribution of the concentration ratio, when combined with a dataset with a positive rate higher than 99%. To evaluate the level of accuracy in the estimation, it is desirable to perform a simulation using an artificially generated left-censored dataset that has the identical number of non detects as the actual data. PMID- 26837827 TI - Transport of enterococci and F+ coliphage through the saturated zone of the beach aquifer. AB - Coastal groundwater has been implicated as a source of microbial pollution to recreational beaches. However, there is little work investigating the transport of fecal microbes through beach aquifers where waters of variable salinity are present. In this study, the potential for fecal indicator organisms enterococci (ENT) and F+ coliphage to be transported through marine beach aquifers was investigated. Native sediment and groundwaters were collected from the fresh and saline sections of the subterranean estuary at three beaches along the California coast where coastal communities utilize septic systems for wastewater treatment. Groundwaters were seeded with sewage and removal of F+ coliphage and ENT by the sediments during saturated flow was tested in laboratory column experiments. Removal varied significantly between beach and organism. F+ coliphage was removed to a greater extent than ENT, and removal was greater in saline sediments and groundwater than fresh. At one of the three beaches, a field experiment was conducted to investigate the attenuation of F+ coliphage and ENT down gradient of a septic leach field. ENT were detected up to 24 m from the leach field. The column study and field observations together suggest ENT can be mobile within native aquifer sediments and groundwater under certain conditions. PMID- 26837828 TI - The impact of meteorology on the occurrence of waterborne outbreaks of vero cytotoxin-producing Escherichia coli (VTEC): a logistic regression approach. AB - This study analyses the relationship between meteorological phenomena and outbreaks of waterborne-transmitted vero cytotoxin-producing Escherichia coli (VTEC) in the Republic of Ireland over an 8-year period (2005-2012). Data pertaining to the notification of waterborne VTEC outbreaks were extracted from the Computerised Infectious Disease Reporting system, which is administered through the national Health Protection Surveillance Centre as part of the Health Service Executive. Rainfall and temperature data were obtained from the national meteorological office and categorised as cumulative rainfall, heavy rainfall events in the previous 7 days, and mean temperature. Regression analysis was performed using logistic regression (LR) analysis. The LR model was significant (p < 0.001), with all independent variables: cumulative rainfall, heavy rainfall and mean temperature making a statistically significant contribution to the model. The study has found that rainfall, particularly heavy rainfall in the preceding 7 days of an outbreak, is a strong statistical indicator of a waterborne outbreak and that temperature also impacts waterborne VTEC outbreak occurrence. PMID- 26837829 TI - Water, sanitation and hygiene for homeless people. AB - This short communication provides insights into water, sanitation and hygiene (WASH) for homeless people through a scoping study conducted in Dhaka, Bangladesh. It investigates homeless access to WASH through the lens of a rights based approach. It demonstrates that homeless people's denial of their right to WASH reflects their marginal position in society and an unequal distribution of power and opportunities. The study ultimately suggests a rights-based approach to work toward dealing with the root causes of discrimination and marginalisation rather than just the symptoms. For the homeless, who not only lack substantive rights, but also the means through which to claim their rights, an integrated rights-based approach to WASH offers the possibility for social inclusion and significant improvements in their life conditions. Given the unique deprivation of homelessness it is argued that in addressing the lack of access to adequate WASH for homeless people the immediate goal should be the fulfilment and protection of the right to adequate shelter. PMID- 26837830 TI - Waterborne microorganisms and biofilms related to hospital infections: strategies for prevention and control in healthcare facilities. AB - Water is the main stimulus for the development of microorganisms, and its flow has an important role in the spreading of contaminants. In hospitals, the water distribution system requires special attention since it can be a source of pathogens, including those in the form of biofilms often correlated with resistance of microorganisms to various treatments. In this paper, information relevant to cases of nosocomial infections involving water circuits as a source of contaminants is compiled, with emphasis on the importance of microbiological control strategies to prevent the installation, spreading and growth of microorganisms in hospitals. An overview of the worldwide situation is provided, with emphasis on Brazilian hospitals. Different approaches normally used to control the occurrence of nosocomial infections due to waterborne contaminants are analyzed, and the use of the polysaccharide chitosan for this specific application is briefly discussed. PMID- 26837832 TI - Using probabilities of enterococci exceedance and logistic regression to evaluate long term weekly beach monitoring data. AB - Recreational water quality surveillance involves comparing bacterial levels to set threshold values to determine beach closure. Bacterial levels can be predicted through models which are traditionally based upon multiple linear regression. The objective of this study was to evaluate exceedance probabilities, as opposed to bacterial levels, as an alternate method to express beach risk. Data were incorporated into a logistic regression for the purpose of identifying environmental parameters most closely correlated with exceedance probabilities. The analysis was based on 7,422 historical sample data points from the years 2000 2010 for 15 South Florida beach sample sites. Probability analyses showed which beaches in the dataset were most susceptible to exceedances. No yearly trends were observed nor were any relationships apparent with monthly rainfall or hurricanes. Results from logistic regression analyses found that among the environmental parameters evaluated, tide was most closely associated with exceedances, with exceedances 2.475 times more likely to occur at high tide compared to low tide. The logistic regression methodology proved useful for predicting future exceedances at a beach location in terms of probability and modeling water quality environmental parameters with dependence on a binary response. This methodology can be used by beach managers for allocating resources when sampling more than one beach. PMID- 26837831 TI - Bidet toilet seats with warm-water tanks: residual chlorine, microbial community, and structural analyses. AB - Despite the reported health-related advantages of the use of warm water in bidets, there are health-related disadvantages associated with the use of these toilet seats, and the bacterial research is sparse. We conducted a survey on the hygienic conditions of 127 warm-water bidet toilet seats in restrooms on a university campus. The spray water from the toilet seats had less residual chlorine than their tap water sources. However, the total viable microbial count was below the water-quality standard for tap water. In addition, the heat of the toilet seats' warm-water tanks caused heterotrophic bacteria in the source tap water to proliferate inside the nozzle pipes and the warm-water tanks. Escherichia coli was detected on the spray nozzles of about 5% of the toilet seats, indicating that the self-cleaning mechanism of the spray nozzles was largely functioning properly. However, Pseudomonas aeruginosa was detected on about 2% of the toilet seats. P. aeruginosa was found to remain for long durations in biofilms that formed inside warm-water tanks. Infection-prevention measures aimed at P. aeruginosa should receive full consideration when managing warm-water bidet toilet seats in hospitals in order to prevent opportunistic infections in intensive care units, hematology wards, and other hospital locations. PMID- 26837833 TI - Removal of arsenic and iron removal from drinking water using coagulation and biological treatment. AB - Effects of biological activated carbon (BAC), biological aerated filter (BAF), alum coagulation and Moringa oleifera coagulation were investigated to remove iron and arsenic contaminants from drinking water. At an initial dose of 5 mg/L, the removal efficiency for arsenic and iron was 63% and 58% respectively using alum, and 47% and 41% respectively using Moringa oleifera. The removal of both contaminants increased with the increase in coagulant dose and decrease in pH. Biological processes were more effective in removing these contaminants than coagulation. Compared to BAF, BAC gave greater removal of both arsenic and iron, removing 85% and 74%, respectively. Longer contact time for both processes could reduce the greater concentration of arsenic and iron contaminants. The addition of coagulation (at 5 mg/L dosage) and a biological process (with 15 or 60 min contact time) could significantly increase removal efficiency, and the maximum removal was observed for the combination of alum and BAC treatment (60 min contact time), with 100% and 98.56% for arsenic and iron respectively. The reduction efficiency of arsenic and iron reduced with the increase in the concentration of dissolved organics in the feedwater due to the adsorption competition between organic molecules and heavy metals. PMID- 26837834 TI - Predicting 'very poor' beach water quality gradings using classification tree. AB - A beach water quality prediction system has been developed in Hong Kong using multiple linear regression (MLR) models. However, linear models are found to be weak at capturing the infrequent 'very poor' water quality occasions when Escherichia coli (E. coli) concentration exceeds 610 counts/100 mL. This study uses a classification tree to increase the accuracy in predicting the 'very poor' water quality events at three Hong Kong beaches affected either by non-point source or point source pollution. Binary-output classification trees (to predict whether E. coli concentration exceeds 610 counts/100 mL) are developed over the periods before and after the implementation of the Harbour Area Treatment Scheme, when systematic changes in water quality were observed. Results show that classification trees can capture more 'very poor' events in both periods when compared to the corresponding linear models, with an increase in correct positives by an average of 20%. Classification trees are also developed at two beaches to predict the four-category Beach Water Quality Indices. They perform worse than the binary tree and give excessive false alarms of 'very poor' events. Finally, a combined modelling approach using both MLR model and classification tree is proposed to enhance the beach water quality prediction system for Hong Kong. PMID- 26837835 TI - A pilot-scale study of Cryptosporidium-sized microsphere removals from swimming pools via sand filtration. AB - Cryptosporidium species are the most common cause of gastrointestinal illness in treated recreational water venues. In order to protect public health during swimming, Cryptosporidium-sized microsphere removals by high-rate sand filtration with six coagulants were evaluated with a 5.5 m(3) pilot-scale swimming pool. A sand filter without coagulation removed 20-63% of Cryptosporidium-sized microspheres. Cryptosporidium-sized microsphere removals exceeded 98% by sand filtration with five of the six tested coagulants. Continuously feeding coagulants A, B, and F (i.e., organic polymers) led to coagulant accumulation in the system and decreased removals over time (<2 days). Coagulant E (polyaluminum chloride) consistently removed more than 90% of microspheres at 30 m/h while the removals dropped to approximately 50% at a filtration rate of 37 m/h. Coagulant C was a chitosan-based product that removed fewer microspheres compared with other products, <75%, under the studied conditions. Results indicated aluminum-based coagulants (coagulants D and E) had an overall performance advantage over the organic polymer based coagulants primarily in terms of their tendency not to accumulate in the water and cease to be effective at improving filter efficiency. PMID- 26837836 TI - Comparison of Colilert-18 with miniaturised most probable number method for monitoring of Escherichia coli in bathing water. AB - The purpose of this equivalence study was to compare an alternative method, Colilert-18 Quanti-Tray (ISO 9308-2) with the European bathing water directive (2006/7/EC) reference method, the miniaturised most probable number (MMPN) method (ISO 9308-3), for the analysis of Escherichia coli. Six laboratories analysed a total of 263 bathing water samples in Finland. The comparison was carried out according to ISO 17994:2004. The recovery of E. coli using the Colilert-18 method was 7.0% and 8.6% lower than that of the MMPN method after 48 hours and 72 hours of incubation, respectively. The confirmation rate of presumptive E. coli positive wells in the Colilert-18 and MMPN methods was high (97.8% and 98.0%, respectively). However, the testing of presumptive E. coli-negative but coliform bacteria-positive (yellow but not fluorescent) Colilert-18 wells revealed 7.3% false negative results. There were more false negatives in the naturally contaminated waters than in the samples spiked with waste water. The difference between the recovery of Colilert-18 and the MMPN method was considered not significant, and subsequently the methods are considered as equivalent for bathing water quality monitoring in Finland. Future bathing water method equivalence verification studies may use the data reported herein. The laboratories should make sure that any wells showing even minor fluorescence will be determined as positive for E. coli. PMID- 26837838 TI - Enteric viruses in surface water and sediment samples from the catchment area of Peri Lagoon, Santa Catarina State, Brazil. AB - This paper aims to quantify human adenovirus (HAdV), rotavirus species A (RVA), and hepatitis A virus (HAV) in surface water and sediments and to determine the viability of HAdV in these samples. Water and sediment samples were collected, and HAdV, RVA, and HAV were quantified by real-time polymerase chain reaction (PCR); HAdV was also evaluated for infectivity by a plaque assay (PA). For the water samples, HAdV was detected in 70.8% of the summer collections, with 82.4% containing infectious HAdV; the HAdV incidence in winter was 62.5%. For the sediment samples, the incidence of HAdV was 37.5% in the summer collections, with 66.7% containing infectious HAdV; the HAdV incidence in winter was 37.5%. RVA was detected in 20.8 and 45.8% of surface water samples collected in summer and winter, respectively, and 8.3 and 12.5% of sediment samples collected in summer and winter, respectively. HAV was detected only in surface waters, with 54.8 and 12.5% positivity in summer and winter samples, respectively. This study demonstrated that enteric viruses are present in water and sediments and that the presence of infectious viruses should be investigated whenever possible for quantitative microbial risk assessment studies. Combined analyses of water and sediments are important for reliable public health risk analysis of recreational and lagoon waters. PMID- 26837837 TI - Impact of providing in-home water service on the rates of infectious diseases: results from four communities in Western Alaska. AB - Approximately 20% of rural Alaskan homes lack in-home piped water; residents haul water to their homes. The limited quantity of water impacts the ability to meet basic hygiene needs. We assessed rates of infections impacted by water quality (waterborne, e.g. gastrointestinal infections) and quantity (water-washed, e.g. skin and respiratory infections) in communities transitioning to in-home piped water. Residents of four communities consented to a review of medical records 3 years before and after their community received piped water. We selected health encounters with ICD-9CM codes for respiratory, skin and gastrointestinal infections. We calculated annual illness episodes for each infection category after adjusting for age. We obtained 5,477 person-years of observation from 1032 individuals. There were 9,840 illness episodes with at least one ICD-9CM code of interest; 8,155 (83%) respiratory, 1,666 (17%) skin, 241 (2%) gastrointestinal. Water use increased from an average 1.5 gallons/capita/day (g/c/d) to 25.7 g/c/d. There were significant (P-value < 0.05) declines in respiratory (16, 95% confidence interval (CI): 11-21%), skin (20, 95%CI: 10-30%), and gastrointestinal infections (38, 95%CI: 13-55%). We demonstrated significant declines in respiratory, skin and gastrointestinal infections among individuals who received in-home piped water. This study reinforces the importance of adequate quantities of water for health. PMID- 26837839 TI - Assessing protozoan risks for surface drinking water supplies in Nova Scotia, Canada. AB - Protozoa, such as Cryptosporidium parvum and Giardia lamblia, pose a human health risk when present in drinking water. To minimize health risks, the Nova Scotia Treatment Standards for surface water and groundwater under the direct influence of surface water require a 3-log reduction for Giardia cysts and Cryptosporidium oocysts. This study determined the protozoan risk of municipal surface source waters in Nova Scotia, through the use of a pre-screening risk analysis of water supplies, followed by subsequent water quality analysis of the seven highest risk supplies. The water supplies were monitored monthly for 1 year to obtain baseline data that could be used for a quantitative microbial risk assessment (QMRA). The QMRA model outcomes were compared to the Health Canada health target of 10(-6) disability-adjusted life years/person/year. QMRA modeling shows that the treatment facilities meet the required log reductions and disability-adjusted life year target standards under current conditions. Furthermore, based on the results of this work, Nova Scotia should maintain the current 3-log reduction standard for Giardia cysts and Cryptosporidium oocysts. The results of this study show that a pre-screening step can help to inform water sources that are particularly vulnerable to protozoan contamination, which can lead to more focused, cost-effective sampling, and monitoring programs. PMID- 26837840 TI - 2, 3-Dimethylmaleic anhydride (3, 4-Dimethyl-2, 5-furandione): A plant derived insecticidal molecule from Colocasia esculenta var. esculenta (L.) Schott. AB - The phasing out of methyl bromide as a fumigant, resistance problems with phosphine and other fumigants in stored product beetles, and serious concern with human health and environmental safety have triggered the search for alternative biofumigants of plant origin. Despite the identification of a large number of plants that show insecticidal activity, and the diversity of natural products with inherent eco-friendly nature, newer biofumigants of plant origin have eluded discovery. Using a bioassay driven protocol, we have now isolated a bioactive molecule from the root stock of Colocasia esculenta (L.) and characterized it as 2, 3-dimethylmaleic anhydride (3, 4-dimethyl-2, 5-furandione) based on various physico-chemical and spectroscopic techniques (IR, (1)H NMR, (13)C NMR and Mass). The molecule proved to be an efficient biofumigant which is highly toxic to insect pests for stored grains even at very low concentration, but has no adverse effect on seed germination. We finally address the potential for this molecule to become a, effective biofumigant. PMID- 26837841 TI - The nuclear protein GmbZIP110 has transcription activation activity and plays important roles in the response to salinity stress in soybean. AB - Plant basic-leucine zipper (bZIP) transcription factors play important roles in many biological processes and are involved in the regulation of salt stress tolerance. Previously, our lab generated digital gene expression profiling (DGEP) data to identify differentially expressed genes in a salt-tolerant genotype of Glycine soja (STGoGS) and a salt-sensitive genotype of Glycine max (SSGoGM). This DGEP data revealed that the expression (log2 ratio) of GmbZIP110 was up-regulated 2.76-fold and 3.38-fold in SSGoGM and STGoGS, respectively. In the present study, the salt inducible gene GmbZIP110 was cloned and characterized through phylogenetic analysis, subcellular localization and in silico transcript abundance analysis in different tissues. The functional role of this gene in salt tolerance was studied through transactivation analysis, DNA binding ability, expression in soybean composite seedlings and transgenic Arabidopsis, and the effect of GmbZIP110 on the expression of stress-related genes in transgenic Arabidopsis was investigated. We found that GmbZIP110 could bind to the ACGT motif, impact the expression of many stress-related genes and the accumulation of proline, Na(+) and K(+), and enhanced the salt tolerance of composite seedlings and transgenic Arabidopsis. Integrating all these results, we propose that GmbZIP110 plays a critical role in the response to salinity stress in soybean and has high potential usefulness in crop improvement. PMID- 26837842 TI - Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. AB - In the phase 3 Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study, nilotinib resulted in earlier and higher response rates and a lower risk of progression to accelerated phase/blast crisis (AP/BC) than imatinib in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). Here, patients' long-term outcomes in ENESTnd are evaluated after a minimum follow-up of 5 years. By 5 years, more than half of all patients in each nilotinib arm (300 mg twice daily, 54%; 400 mg twice daily, 52%) achieved a molecular response 4.5 (MR(4.5); BCR-ABL?0.0032% on the International Scale) compared with 31% of patients in the imatinib arm. A benefit of nilotinib was observed across all Sokal risk groups. Overall, safety results remained consistent with those from previous reports. Numerically more cardiovascular events (CVEs) occurred in patients receiving nilotinib vs imatinib, and elevations in blood cholesterol and glucose levels were also more frequent with nilotinib. In contrast to the high mortality rate associated with CML progression, few deaths in any arm were associated with CVEs, infections or pulmonary diseases. These long-term results support the positive benefit-risk profile of frontline nilotinib 300 mg twice daily in patients with CML-CP. PMID- 26837843 TI - Differential impact of additional chromosomal abnormalities in myeloid vs lymphoid blast phase of chronic myelogenous leukemia in the era of tyrosine kinase inhibitor therapy. PMID- 26837845 TI - Do short, frequent DNA sequence motifs mould the epigenome? AB - 'Epigenome' refers to the panoply of chemical modifications borne by DNA and its associated proteins that locally affect genome function. Epigenomic patterns are thought to be determined by external constraints resulting from development, disease and the environment, but DNA sequence is also a potential influence. We propose that domains of relatively uniform DNA base composition may modulate the epigenome through cell type-specific proteins that recognize short, frequent sequence motifs. Differential recruitment of epigenomic modifiers may adjust gene expression in multigene blocks as an alternative to tuning the activity of each gene separately, thus simplifying gene expression programming. PMID- 26837846 TI - Stabilization of active matter by flow-vortex lattices and defect ordering. AB - Active systems, from bacterial suspensions to cellular monolayers, are continuously driven out of equilibrium by local injection of energy from their constituent elements and exhibit turbulent-like and chaotic patterns. Here we demonstrate both theoretically and through numerical simulations, that the crossover between wet active systems, whose behaviour is dominated by hydrodynamics, and dry active matter where any flow is screened, can be achieved by using friction as a control parameter. Moreover, we discover unexpected vortex ordering at this wet-dry crossover. We show that the self organization of vortices into lattices is accompanied by the spatial ordering of topological defects leading to active crystal-like structures. The emergence of vortex lattices, which leads to the positional ordering of topological defects, suggests potential applications in the design and control of active materials. PMID- 26837848 TI - Powder metallurgy inspired low-temperature fabrication of high-performance stereocomplexed polylactide products with good optical transparency. AB - Stereocomplexation between enantiomeric poly(l-lactide) (PLLA) and poly(d lactide) (PDLA) provides an avenue to greatly enhance performance of eco-friendly polylactide (PLA). Unfortunately, although the manufacturing of semicrystalline polymers generally involves melt processing, it is still hugely challenging to create high-performance stereocomplexed polylactide (sc-PLA) products from melt processed high-molecular-weight PLLA/PDLA blends due to the weak crystallization memory effect of stereocomplex (sc) crystallites after complete melting as well as the substantial degradation of PLA chains at elevated melt-processing temperatures of ca. 240-260 degrees C. Inspired by the concept of powder metallurgy, here we report a new facile route to address these obstacles by sintering of sc-PLA powder at temperatures as low as 180-210 degrees C, which is distinctly different from traditional sintering of polymer powders performed at temperatures far exceeding their melting temperatures. The enantiomeric PLA chain segments from adjacent powder particles can interdiffuse across particle interfaces and co-crystallize into new sc crystallites capable of tightly welding the interfaces during the low-temperature sintering process, and thus highly transparent sc-PLA products with outstanding heat resistance, mechanical strength, and hydrolytic stability have been successfully fabricated for the first time. PMID- 26837849 TI - Bioethics meets Ebola: exploring the moral landscape. AB - INTRODUCTION: The Ebola Virus Disease (EVD) outbreak in West Africa raised ethical issues about structural disadvantage; the duty to care of healthcare workers; the use and study of unregistered agents; the use of restrictive measures like mass quarantine and the importance of public trust. SOURCES OF DATA: WHO reports, literature on EVD and ethics. AREAS OF AGREEMENT: The use of restrictive measures and the testing of unregistered agents is ethical if support for individuals or communities is provided. AREAS OF CONTROVERSY: Controversy exists over ethical trial design for the study of unregistered agents and over the limits of the duty to care. GROWING POINTS: The role of the WHO in outbreak control and research oversight needs rethinking and further support. Solidarity in global health needs fostering. AREAS TIMELY FOR DEVELOPING RESEARCH: Research is needed on how to restore and enhance health systems and public trust in EVD affected countries. PMID- 26837847 TI - The miR-130 family promotes cell migration and invasion in bladder cancer through FAK and Akt phosphorylation by regulating PTEN. AB - Bladder cancer causes an estimated 150,000 deaths per year worldwide. Although 15% of the recurrent bladder cancer becomes an invasive type, currently used targeted therapy for malignant bladder cancer is still not efficient. We focused on the miR-130 family (miR-130b, miR-301a, and miR-301b) that was significantly upregulated in bladder cancer specimens than that of the normal urothelial specimens. We analyzed the functional significance of miR-130 family using a 5637 bladder cancer cell line and revealed that miR-130 family of inhibitors suppressed cell migration and invasion by downregulating focal adhesion kinase (FAK) and Akt phosphorylation. Mechanistic analyses indicate that the miR-130 family directly targets phosphatase and tensin homolog deleted from chromosome 10 (PTEN), resulting in the upregulation of FAK and Akt phosphorylation. In clinical bladder cancer specimens, downregulation of PTEN was found to be closely correlated with miR-130 family expression levels. Overall, the miR-130 family has a crucial role in malignant progression of bladder cancer and thus the miR-130 family could be a promising therapeutic target for invasive bladder cancer. PMID- 26837850 TI - Regeneration techniques for bone-to-tendon and muscle-to-tendon interfaces reconstruction. AB - INTRODUCTION: The complex structure of the bone-tendon and muscle-tendon junctions makes their reproduction for tissue engineering applications very difficult. Relatively few studies have investigated the characteristics of these regions from a tissue engineering view point. SOURCES OF DATA: PubMed, Thomson Reuters, Scopus and Google Scholar databases were searched using various combinations of the keywords 'Tendon', 'Myotendinous junction', 'Osteotendinous junction', 'Tissue engineering' and 'Scaffold'. AREAS OF AGREEMENT: The available studies can be divided according to whether the objective is to build an entire composite tissue unit or to assist the recreation of interfaces, such as improving integration of autografts with the surrounding bone or with the muscle. The most used techniques are based on the electrospinning and the self reorganized constructs process, which were applied to both bone-to-tendon junction (BTJ) and muscle-to-tendon junction (MTJ) regeneration. The use of nanofibers that mimic the hierarchical structure of the extracellular matrix (ECM), eventually functionalized by encapsulation of bioactive components, allowed cell attachment and differentiation. AREAS OF CONTROVERSY: There have been no translational investigations. GROWING POINTS: There is a need to devise suitable techniques that allow suitable tissue engineering of BTJ and MTJ. AREAS TIMELY FOR DEVELOPING RESEARCH: Appropriately planned studies are needed to translate tissue engineering from a scientific challenge to a clinically applicable technique. PMID- 26837851 TI - Facing the fear--clinical and neural effects of cognitive behavioural and pharmacotherapy in panic disorder with agoraphobia. AB - INTRODUCTION: Cognitive behavioural therapy (CBT) and pharmacological treatment with selective serotonin or serotonin-noradrenalin reuptake inhibitors (SSRI/SSNRI) are regarded as efficacious treatments for panic disorder with agoraphobia (PD/AG). However, little is known about treatment-specific effects on symptoms and neurofunctional correlates. EXPERIMENTAL PROCEDURES: We used a comparative design with PD/AG patients receiving either two types of CBT (therapist-guided (n=29) or non-guided exposure (n=22)) or pharmacological treatment (SSRI/SSNRI; n=28) as well as a wait-list control group (WL; n=15) to investigate differential treatment effects in general aspects of fear and depression (Hamilton Anxiety Rating Scale HAM-A and Beck Depression Inventory BDI), disorder-specific symptoms (Mobility Inventory MI, Panic and Agoraphobia Scale subscale panic attacks PAS-panic, Anxiety Sensitivity Index ASI, rating of agoraphobic stimuli) and neurofunctional substrates during symptom provocation (Westphal-Paradigm) using functional magnetic resonance imaging (fMRI). Comparisons of neural activation patterns also included healthy controls (n=29). RESULTS: Both treatments led to a significantly greater reduction in panic attacks, depression and general anxiety than the WL group. The CBT groups, in particular, the therapist-guided arm, had a significantly greater decrease in avoidance, fear of phobic situations and anxiety symptoms and reduction in bilateral amygdala activation while the processing of agoraphobia-related pictures compared to the SSRI/SSNRI and WL groups. DISCUSSION: This study demonstrates that therapist-guided CBT leads to a more pronounced short-term impact on agoraphobic psychopathology and supports the assumption of the amygdala as a central structure in a complex fear processing system as well as the amygdala's involvement in the fear system's sensitivity to treatment. PMID- 26837853 TI - Relationships between left atrial pericardial fat and permanent atrial fibrillation: Results of a case-control study. AB - PURPOSE: The goal of this study was to retrospectively investigate the relationships between pericardial fat, left atrium volume (LAV) as measured on multidetector row computed tomography (MDCT) and persistent atrial fibrillation (AF) using a case-control study. MATERIALS AND METHODS: The study population consisted of 58 patients (19 men, 39 women; mean age, 67.8+/-10 [SD] years) with persistent AF and 74 control subjects (30 men, 44 women; mean age, 67.8+/-10.9 [SD] years). The associations between the presence of persistent AF and periatrial pericardial fat volume (PAFV), periatrial pericardial fat thickness (PAFT), and LAV as measured on MDCT were searched for using univariate and multiple linear regression analysis. RESULTS: On univariate analysis, significant differences were found between patients with AF and control subjects for mean PAFV (54.33cm(3)+/-23.43 [SD]; range: 12.2-111.1cm(3) vs 42.99cm(3)+/-20.76 [SD]; range: 7.4-103.9cm(3), respectively) (P=0.01), PAFT at the esophagus (1.87mm+/ 1.65 [SD]; range: 0.1-9.5mm vs 1.12mm+/-0.77 [SD]; range: 0.1-3.6mm, respectively) (P<0.001) and normalized LAV (78.3cm(3)/m(2)+/-48.84 [SD]; range: 32.1-319.6cm(3)/m(2) vs 42.1cm(3)/m(2)+/-25.43 [SD]; range: 15.7-191.4cm(3)/m(2), respectively) (P<0.001). Multiple linear regression analysis revealed that only LAV was an independent predictor (P<0.001) of persistent AF. Also PAFV was significantly associated with LAV (P=0.01). CONCLUSION: LAV is greater in patients with AF than in control subjects and PAFV is strongly associated with LAV. PAFV and PAFT are not independently associated with AF. PMID- 26837854 TI - Prenatal diagnosis of complete nonrotation of fetal bowel with ultrasound and magnetic resonance imaging. PMID- 26837852 TI - Curcumin Nanoformulation for Cervical Cancer Treatment. AB - Cervical cancer is one of the most common cancers among women worldwide. Current standards of care for cervical cancer includes surgery, radiation, and chemotherapy. Conventional chemotherapy fails to elicit therapeutic responses and causes severe systemic toxicity. Thus, developing a natural product based, safe treatment modality would be a highly viable option. Curcumin (CUR) is a well known natural compound, which exhibits excellent anti-cancer potential by regulating many proliferative, oncogenic, and chemo-resistance associated genes/proteins. However, due to rapid degradation and poor bioavailability, its translational and clinical use has been limited. To improve these clinically relevant parameters, we report a poly(lactic-co-glycolic acid) based curcumin nanoparticle formulation (Nano-CUR). This study demonstrates that in comparison to free CUR, Nano-CUR effectively inhibits cell growth, induces apoptosis, and arrests the cell cycle in cervical cancer cell lines. Nano-CUR treatment modulated entities such as miRNAs, transcription factors, and proteins associated with carcinogenesis. Moreover, Nano-CUR effectively reduced the tumor burden in a pre-clinical orthotopic mouse model of cervical cancer by decreasing oncogenic miRNA-21, suppressing nuclear beta-catenin, and abrogating expression of E6/E7 HPV oncoproteins including smoking compound benzo[a]pyrene (BaP) induced E6/E7 and IL-6 expression. These superior pre-clinical data suggest that Nano-CUR may be an effective therapeutic modality for cervical cancer. PMID- 26837855 TI - Identifying waking time in 24-h accelerometry data in adults using an automated algorithm. AB - As accelerometers are commonly used for 24-h measurements of daily activity, methods for separating waking from sleeping time are necessary for correct estimations of total daily activity levels accumulated during the waking period. Therefore, an algorithm to determine wake and bed times in 24-h accelerometry data was developed and the agreement of this algorithm with self-report was examined. One hundred seventy-seven participants (aged 40-75 years) of The Maastricht Study who completed a diary and who wore the activPAL3TM 24 h/day, on average 6 consecutive days were included. Intraclass correlation coefficient (ICC) was calculated and the Bland-Altman method was used to examine associations between the self-reported and algorithm-calculated waking hours. Mean self reported waking hours was 15.8 h/day, which was significantly correlated with the algorithm-calculated waking hours (15.8 h/day, ICC = 0.79, P = < 0.001). The Bland-Altman plot indicated good agreement in waking hours as the mean difference was 0.02 h (95% limits of agreement (LoA) = -1.1 to 1.2 h). The median of the absolute difference was 15.6 min (Q1-Q3 = 7.6-33.2 min), and 71% of absolute differences was less than 30 min. The newly developed automated algorithm to determine wake and bed times was highly associated with self-reported times, and can therefore be used to identify waking time in 24-h accelerometry data in large scale epidemiological studies. PMID- 26837856 TI - [Parotid mass as presenting symptom of Hodgkin lymphoma]. PMID- 26837857 TI - [A disturbing electrocardiogram: Inverted T waves in the left precordial leads of an African-American athlete]. PMID- 26837858 TI - [Efficacy of percutaneous coronary intervention in patients with chronic ischaemic heart disease]. PMID- 26837859 TI - Growth of Ehrlichia canis, the causative agent of canine monocytic ehrlichiosis, in vector and non-vector ixodid tick cell lines. AB - Canine monocytic ehrlichiosis is caused by Ehrlichia canis, a small gram-negative coccoid bacterium that infects circulating monocytes. The disease is transmitted by the brown dog tick Rhipicephalus sanguineus s.l. and is acknowledged as an important infectious disease of dogs and other members of the family Canidae worldwide. E. canis is routinely cultured in vitro in the canine monocyte macrophage cell line DH82 and in non-vector Ixodes scapularis tick cell lines, but not in cells derived from its natural vector. Here we report infection and limited propagation of E. canis in the tick cell line RSE8 derived from the vector R. sanguineus s.l., and successful propagation through six passages in a cell line derived from the experimental vector Dermacentor variabilis. In addition, using bacteria semi-purified from I. scapularis cells we attempted to infect a panel of cell lines derived from non-vector species of the tick genera Amblyomma, Dermacentor, Hyalomma, Ixodes and Rhipicephalus with E. canis and, for comparison, the closely-related Ehrlichia ruminantium, causative agent of heartwater in ruminants. Amblyomma and non-vector Dermacentor spp. cell lines appeared refractory to infection with E. canis but supported growth of E. ruminantium, while some, but not all, cell lines derived from Hyalomma, Ixodes and Rhipicephalus spp. ticks supported growth of both pathogens. We also illustrated and compared the ultrastructural morphology of E. canis in DH82, RSE8 and I. scapularis IDE8 cells. This study confirms that E. canis, like E. ruminantium, is able to grow not only in cell lines derived from natural and experimental tick vectors but also in a wide range of other cell lines derived from tick species not known to transmit this pathogen. PMID- 26837860 TI - Molecular detection of bacteria in the families Rickettsiaceae and Anaplasmataceae in northern crested caracaras (Caracara cheriway). AB - Bacterial pathogens of the families Anaplasmataceae and Rickettsiaceae are often spread to humans or other animals from bites from infected arthropod hosts. Recently, an increasing number of studies have implicated migratory birds in the circulation of these pathogens through the spread of arthropod vectors. However, few studies have examined the potential for resident bird populations to serve as reservoirs for these zoonoses. In this study, we used nested PCRs of the GroESL and 17 kDa genes to screen for Anaplasmataceae and Rickettsiaceae, respectively, in a resident population of the northern crested caracara (Caracara cheriway) from Florida (n=55). Additionally, a small number (n=6) of captive individuals from Texas were included. We identified one individual (1.64%) positive for Rickettsia felis and one (1.64%) positive for Ehrlichia chaffeensis; both these individuals were from Florida. Presence of these pathogens demonstrates that these birds are potential hosts; however, the low prevalence of infections suggests that these populations likely do not function as an ecological reservoir. PMID- 26837861 TI - Tubal cytokine changes accompany the epithelial atypia of letrozole-stimulated ovaries. AB - Letrozole (LTZ), one of ovulation induction medications, is increasingly prescribed in many gynecological conditions. Although its hazardous effect on the ovarian surface epithelium (OSE) as well as tubal epithelium cells (TEC) has been previously studied, the associated changes occurring in the inflammatory cytokines have not been elucidated. Therefore, the objective of our study is to investigate these changes that may accompany LTZ-induced tubo-ovarian epithelial abnormalities. A total of 45 Sprague-Dawley rats were used in this study, divided equally into; control, LTZ6 and LTZ12 groups (received saline, 6 and 12 cycles LTZ i.p. respectively). Samples from ovaries (OVs) as well as fallopian tubes (FTs) were histologically studied for the associated changes. An increased proliferative activity, Ki67 immunoexpression and abnormal invaginations were observed in the OSE of LTZ6 group accompanied with occasional pseudostratification and loss of cilia of TEC. These changes became more pronounced in the LTZ12 where micropapillae, hyperchromasia, frequent deep invaginations, cysts of OSE as well as papillae and multilayering of TEC were noticed. The tubal level of IL-1beta, IL-6, TNF-alpha and serum MCP-1 progressively increased in LTZ6 and LTZ12 groups compared with the control group. The significant positive correlation observed between these cytokines in the LTZ6 group became stronger in the LTZ12 one. However, no significant changes in the tubal IL-10 and TGF-beta were detected. Therefore, further studies are required to consider these cytokines as objective markers to precisely assess severity of the associated epithelial changes particularly in long periods of stimulation. PMID- 26837863 TI - Other diagnostic methods with high sensitivity can be used to differentiate Takotsubo cardiomyopathy from acute coronary syndrome. PMID- 26837862 TI - Preclinical safety evaluation of recombinant adeno-associated virus 2 vector encoding human tumor necrosis factor receptor-immunoglobulin Fc fusion gene. AB - Recombinant adeno-associated virus (rAAV) 2 vector gene therapy offers promise for the healing of Rheumatoid arthritis. To support the clinical development of the candidate gene therapeutic product in China, a comprehensive preclinical safety assessment of rAAV2 encoding human TNF receptor-immunoglobulin Fc fusion gene (rAAV2/human TNFR:Fc), were conducted in 3 species of experimental animals. No abnormal findings were observed in mice following single intravenous administration with test article. Compared with the control group, no differences in mean body weight, food consumption in rats and monkeys following the repeated intraarticular administration with rAAV2/human TNFR:Fc. There were also no significant adverse effects due to treatment noted by clinical chemistry, hematology and pathology assessments. After intraarticular administration with rAAV2/human TNFR:Fc, the vector DNA initially distributed to spleen, lymph nodes, and joint synovium. The vector DNA cleared rapidly as it could be detected mainly at the site of injection by 91 d post-administration (182 d for monkey). Taken together, localized delivery of rAAV2/human TNFR:Fc showed no significant toxicity in mice, rats, and monkeys, which support the planned clinical evaluation of this product. PMID- 26837864 TI - Polypharmacy in heart failure - Is reducing medication safe? PMID- 26837865 TI - [Non-invasive and invasive out of hospital ventilation in chronic respiratory failure : Consensus report of the working group on ventilation and intensive care medicine of the Austrian Society of Pneumology]. AB - The current consensus report was compiled under the patronage of the Austrian Society of Pneumology (Osterreichischen Gesellschaft fur Pneumologie, OGP) with the intention of providing practical guidelines for out-of-hospital ventilation that are in accordance with specific Austrian framework parameters and legal foundations. The guidelines are oriented toward a 2004 consensus OGP recommendation concerning the setup of long-term ventilated patients and the 2010 German Respiratory Society S2 guidelines on noninvasive and invasive ventilation of chronic respiratory insufficiency, adapted to national experiences and updated according to recent literature. In 11 chapters, the initiation, adjustment, and monitoring of out-of-hospital ventilation is described, as is the technical equipment and airway access. Additionally, the different indications-such as chronic obstructive pulmonary diseases, thoracic restrictive and neuromuscular diseases, obesity hypoventilation syndrome, and pediatric diseases-are discussed. Furthermore, the respiratory physiotherapy of adults and children on invasive and noninvasive long-term ventilation is addressed in detail. PMID- 26837867 TI - Germline RET mutation carriers in Japanese patients with apparently sporadic medullary thyroid carcinoma: A single institution experience. AB - OBJECTIVE: Genetic testing for RET germline mutation can be useful to distinguish whether a patient with medullary thyroid carcinoma (MTC) is genuinely sporadic or hereditary. Conducting a routine preoperative germline RET genetic screening for all patients with MTC has the clinical benefit, i.e., avoidance of unnecessary total thyroidectomy in the selected patients. We sought to clarify the incidence of germline RET mutation carriers in Japanese patients with apparently sporadic MTC and to address the differences in clinicopathological characteristics between true sporadic MTC and hereditary MTC in these patients, all of whom were treated at Kuma Hospital. METHODS: A total of 134 patients with apparently sporadic MTC who underwent surgery between 1996 and 2014 were enrolled. All patients underwent a germline RET gene mutation analysis preoperatively. RESULTS: Germline mutations in RET proto-oncogene were identified in 20 of the 134 (14.9%) apparently sporadic MTC patients. No significant difference in clinicopathological characteristics was observed between the patients with sporadic MTC (n=114) and those with hereditary MTC (n=20) except for the RET gene carriers' younger age at diagnosis and presence of multifocal and bilateral lesions. CONCLUSION: Germline RET mutations were identified in 14.9% of Japanese patients with apparently sporadic MTC. No clearly decisive clinicopathological characteristics was observed to distinguish whether an apparently sporadic MTC case was genuinely sporadic or unconsciously hereditary. For the treatment strategy decision, it is advantageous to conduct a routine preoperative germline RET genetic screening for all patients with MTC, even if their MTC is apparently sporadic. PMID- 26837866 TI - A 6-year follow-up of a large European cohort of children with attention deficit/hyperactivity disorder-combined subtype: outcomes in late adolescence and young adulthood. AB - There are very few studies on the long-term outcome of children and adolescents with ADHD-combined type in Europe. The objective of the present study is to assess the 6-year outcome (including pharmacological treatment) of a large cohort of participants with ADHD-combined type (N = 347, mean age 11.4 years) in late adolescence and early adulthood. At study entry and follow-up (mean age 17.4 years), participants were comprehensively assessed on ADHD and comorbid disorders by structured psychiatric interviews and multi-informant questionnaires. Overall functioning was assessed by the Children's Global Assessment Scale. The retention rate was 75.6 %. The majority of participants (86.5 %) persisted in a DSM-5 ADHD diagnosis, 8.4 % had a subthreshold diagnosis, and 5.1 % remitted from the disorder at follow-up. Comorbidities decreased strongly; oppositional defiant disorder: 58 > 31 %, conduct disorder: 19 > 7 %. At follow-up, mood- and anxiety disorders were virtually non-existent following strict criteria (1-3 %). Percentage of children having had pharmacological treatment at any time increased from 79 to 91 %. On the Children's Global Assessment Scale, 48.5 % of participants were still functionally impaired at follow-up. Parental ADHD, higher ADHD symptom severity at baseline and higher parent-reported impairment at baseline positively predicted current ADHD symptom severity (R (2) = 20.9 %). Younger baseline age, higher ADHD symptom severity at baseline and higher parent reported impairment at baseline were positively associated with poorer overall functioning (R (2) = 17.8 %). Pharmacological treatment had no (beneficial) impact on either ADHD symptom severity or overall functioning. Results confirm that ADHD is largely persistent into late adolescence with severity and family history for the disorder as important risk factors. PMID- 26837868 TI - Clinical features and outcomes of delayed facial palsy after head trauma. AB - OBJECTIVE: To investigate clinical features and outcomes of delayed facial palsy after head trauma. METHODS: The cases who had delayed facial palsy after head trauma treated from March 2008 to March 2013 at our hospital were enrolled in the study, and their clinical features and outcomes were analyzed. RESULTS: Thirty five of 1620 cases developed delayed facial palsy after head trauma. Facial palsy occurred within day 3-7 in 23 cases, during day 8-14 in 8 cases, and 2 weeks later in 4 cases. Thirty-three cases were treated by prednisolone alone, and two cases who showed >=90% degeneration of nerve fibers underwent surgical exploration and decompression. Among the 33 cases who received conservative treatment, 27 cases (81.8%) recovered completely, 3 cases (9.1%) recovered to Grade II, and only 3 cases (9.1%) recovered to Grade III or IV. The two surgically treated patients recovered to Grade II and III, respectively. CONCLUSION: The incidence of delayed facial palsy was 2.2% after head trauma. Delayed facial palsy mainly occurred within 2 weeks after head trauma. And over 90% patients achieved good recovery (HB Grade I or II) of facial nerve after conservative treatment. PMID- 26837869 TI - Stochastic modelling and control of antibiotic subtilin production. AB - A stochastic hybrid model for the production of the antibiotic subtilin by the Bacillus subtilis is investigated. This model consists of 5 variables with four possible discrete dynamical states and this high dimensionality represents a bottleneck for using statistical tools that require to solve the corresponding Fokker-Planck problem. For this reason, a suitable reduced model with 3 variables and two dynamical states is proposed. The corresponding Fokker-Planck hyperbolic system is used to validate the evolution statistics and to construct a robust feedback control strategy to increase subtilin production. Results of numerical experiments are presented that show the effectiveness of the proposed control scheme. PMID- 26837870 TI - [Antibacterial activity of natural compounds - essential oils]. AB - Since the problem of bacterial resistance has become a serious problem worldwide, it was necessary to search for new active substances that can overcome the problem and enhance the treatment efficacy of bacterial infections. Numerous plant-derived essential oils exhibited significant antibacterial activities. This review aimed to summarize the most promising essential oils that exhibited remarkable antibacterial activities against various bacterial infections, including staphylococcal infections, Helicobacter pylori infections, skin infections, tuberculosis infection and dental bacterial infection. The synergy effect of essential oils in combination with antibiotics, as well as their role in the treatment of bacterial infections have been discussed. Essential oils can be used as models for further studies in vivo and clinical trials. PMID- 26837871 TI - [Cholinergic system of the heart]. AB - The cholinergic system of the heart can be either of neuronal or non-neuronal origin. The neuronal cholinergic system in the heart is represented by preganglionic parasympathetic pathways, intracardiac parasympathetic ganglia and postganglionic parasympathetic neurons projecting to the atria, SA node and AV node. The non-neuronal cholinergic system consists of cardiomyocytes that have complete equipment for synthesis and secretion of acetylcholine. Current knowledge suggests that the non-neuronal cholinergic system in the heart affects the regulation of the heart during sympathetic activation. The non-neuronal cholinergic system of the heart plays also a role in the energy metabolism of cardimyocites. Acetylcholine of both neuronal and non-neuronal origin acts in the heart through muscarinic and nicotinic receptors. The effect of acetylcholine in the heart is terminated by cholinesterases acetylcholinesterase and butyrylcholinesterase. Recently, papers suggest that the increased cholinergic tone in the heart by cholinesterase inhibitors has a positive effect on some cardiovascular disorders such as heart failure. For this reason, the cholinesterase inhibitors might be used in the treatment of certain cardiovascular disorders in the future. KEY WORDS: cholinergic system heart innervation non-neuronal cholinergic system of the heart receptors cholinesterases in the heart. PMID- 26837873 TI - Stable gold nanoparticles - synthesis, bioconjugation and application. PMID- 26837872 TI - Povrch tela a telesna hmotnost dospele ceske onkologicke populace. AB - Almost all conventional cytostatics are dosed according to body surface area of the patient. Many monoclonal antibodies are also dosed with respect to body surface area or body weight of the patient. While in some European countries, there is recent information describing the anthropometrics of the cancer population, no data are available for Czech population. That is the reason why body surface area and weight of adult patients who were administered chemotherapy at Masaryk Memorial Cancer Institute in 2013 and 2014 were evaluated. The total number of evaluated patients was 3873, consisting of 2476 women and 1397 men. The mean body surface area was 1.78 m2 (95% confidence interval (CI) 1.77-1.79 m2) for women, 2.00 m2 (95% CI 1.99-2.01 m2) for men, and 1.86 m2 (95% CI 1.85-1.87 m2) in total. The mean body weight was 71.94kg for women (95% CI 71.35-72.53 kg), 83.43kg (95% CI 82.60-84.26 kg) for men, and 76.09kg (95% CI 75.58-76.60 kg) in total. KEY WORDS: body surface area body weight chemotherapy. PMID- 26837874 TI - Determination of antigripal drugs (pheniramine, phenylephrine) in biological samples by on-line CITP-CZE coupled with tandem mass spectrometry. PMID- 26837875 TI - Development of the hydrocortisone butyrate qualitative determination method. PMID- 26837876 TI - Estimation of lipohydrophilic properties of molecules with potential beta3 agonistic activity. PMID- 26837877 TI - Determination of the colorants in vitamin E by HPLC with photodiode array detection. PMID- 26837878 TI - Analysis of flavonoids in grape leaves by HPLC-DAD-MS/MS. PMID- 26837879 TI - Antioxidative protection of inactivated rabies vaccine with squalene adjuvant by beta-carotene. PMID- 26837880 TI - From an old drug to a new one: Synthesis of valproate from 5,5-dipropylbarbituric acid. PMID- 26837881 TI - Synthesis and antimicrobial activity of novel sulfonamide derivatives. PMID- 26837882 TI - Synthesis and antioxidant activity of phenylcarbamic acid derivatives acting on the cardiovascular system. PMID- 26837883 TI - Synthesis and biological activity of selected cinnamic acid derivatives. PMID- 26837884 TI - Synthesis and biological properties of chosen symmetrical amides and thioamides of terephthalic acid. PMID- 26837885 TI - Synthesis of quinoline derivatives using a nano-Pd/Cu catalyst in the search of new fluorophores. PMID- 26837886 TI - Synthesis of triclosan derivatives and their antimycobacterial effect. PMID- 26837887 TI - The development of a dental drug in the form of medicated chewing gum. PMID- 26837889 TI - Dengue and the Olympic and Paralympic Games in Rio 2016: what do athletes, coaches and visitors need to know? PMID- 26837888 TI - The ICl,swell inhibitor DCPIB blocks Kir channels that possess weak affinity for PIP2. AB - Inwardly rectifying K(+) (Kir) channels are important contributors to the resting membrane potential and regulate cellular excitability. The activity of Kir channels depends critically on the phospholipid PIP2. Several modulators of the activity of Kir channels alter the apparent affinity of the channel to PIP2. Channels with high apparent affinity to PIP2 may not respond to a given modulator, but mutations that decrease such affinity can render the channel susceptible to modulation. Here, we identify a known inhibitor of the swelling activated Cl(-) current, DCPIB, as an effective inhibitor of a number of Kir channels both in native cardiac cells and in heterologous expression systems. We show that the apparent affinity to PIP2 determines whether DCPIB will serve as an efficient blocker of Kir channels. These effects are consistent with a model in which DCPIB competes with PIP2 for a common binding site. PMID- 26837890 TI - Respiratory function is associated to marathon race time. AB - BACKGROUND: The purpose of this study was to analyze the relationship between marathon race time and expiratory pulmonary parameters in a heterogeneous group of amateur marathoners. METHODS: A total of 110 marathon runners (age=41.9+/-9.4 yr, body mass=74.0+/-9.1 kg, height=175.0+/-8.0 cm) volunteered to participate in this study. First, they completed a questionnaire about running experience and best performance time in the 10-km, half-marathon and marathon competitions. Then, they performed a maximal spirometry test following guidelines for standardized spirometry. Measurement included peak expiratory flow (PEF), forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC). All these expiratory variables were normalized for the participant's body mass. Within 3 days of the spirometry test, participants competed in an official marathon and race time was measured by a chip-timing. After this, participants were grouped by their marathon race time as follows: <210 min, N.=33; between 210 and 240 min, N.=31; and >240 min, N.=46). RESULTS: Marathon race time correlated to the FVC.kg-1 (r=-0.41; P<0.001), to FEV1.kg-1 (r=-0.40; P<0.001), and PEF.kg-1 (r=-0.50; P=0.005). However, self-reported running experience did not show significant correlations to FVC.kg-1 and PEF.kg-1 (P>0.05). The group of faster marathoners (e.g., <210 min) had greater FEV1.kg-1 (<210 min group: 0.064+/ 0.009; 210-240 min group: 0.058+/-0.008; >240 min group: 0.057+/-0.009; P<0.001) and higher FVC.kg-1 (<210 min group: 0.081+/-0.011; 210-240 min group: 0.075+/ 0.012; >240 min group: 0.072+/-0.010; P<0.001) than the other two groups of slower runners. CONCLUSIONS: These results suggest a significant relationship between individual pulmonary function and marathon race time. Thus, a higher lung capacity per kg of body mass might be a key variable for marathon performance in amateur runners. PMID- 26837891 TI - Modulation of microRNAs expression in hematopoietic stem cells treated with sodium butyrate in inducing fetal hemoglobin expression. AB - Context Inherited hemoglobin diseases are the most common single-gene disorders. Induction of fetal hemoglobin in beta hemoglobin disorders compensate for abnormal chain and ameliorate the clinical complications. Sodium butyrate is used conventionally for fetal hemoglobin induction; it can be replaced by safer therapeutic tools like microRNAs, small non-coding RNAs that control number of epigenetic mechanisms. Objective In this study, we compared the changes in the microRNAs of differentiated erythroid cells between control and sodium butyrate treated groups. The objective is to find significant association between these changes and gamma chain up regulation. Materials and methods First, CD133+ hematopoietic stem cells were isolated from cord blood by magnetic cell sorting (MACS) technique. After proliferation, the cells were differentiated to erythroid lineage in culture medium by EPO, SCF, and IL3. Meanwhile, the test group was treated with sodium butyrate. Then, gamma chain upregulation was verified by qPCR technique. Finally, microRNA profiling was performed through microarray assay and some of them confirmed by qPCR. Result Results demonstrated that gamma chain was 5.9-fold upregulated in the treated group. Significant changes were observed at 76 microRNAs, in which 20 were up-regulated and 56 were down-regulated. Discussion Five of these microRNAs including U101, hsa-miR-4726-5p, hsa-miR7109 5p, hsa-miR3663, and hsa-miR940 had significant changes in expression and volume. Conclusion In conclusion, it can be assumed that sodium butyrate can up-regulate gamma chain gene, and change miRNAs expression. These results can be profitable in future studies to find therapeutic goal suitable for such disorders. PMID- 26837892 TI - Bovine papillomavirus type 7 in Italy: complete genomes and sequence variants. AB - Two novel bovine papillomavirus type 7 (BPV-7) variants have been identified in teat cutaneous papillomas affecting dairy cows in northern Italy. The entire genome sequences of two BPV-7 Italian variants showed major sequence differences in the long control region (LCR) and in the L2 gene compared to the Japanese reference strain. In order to define the stability of these genetic variants, the L2 and LCR sequences of seven further BPV-7 positive isolates were characterized. An insertion of six amino acids in the L2 structural protein has been detected in all samples while different genetic variants have been identified for the LCR. These findings provide new insights on intra-type variability of BPVs and represent a starting point for future studies aimed at establishing the biological role of the different BPV genomic regions and investigating the pathogenic potential of papillomavirus variants. PMID- 26837893 TI - ORF43 of maize rayado fino virus is dispensable for systemic infection of maize and transmission by leafhoppers. AB - Maize rayado fino virus (MRFV) possesses an open reading frame (ORF43) predicted to encode a 43 kDa protein (p43) that has been postulated to be a viral movement protein. Using a clone of MRFV (pMRFV-US) from which infectious RNA can be produced, point mutations were introduced to either prevent initiation from three potential AUG initiation codons near the 5'-end of ORF43 or prematurely terminate translation of ORF43. Inoculation of maize seed via vascular puncture inoculation (VPI) resulted in plants exhibiting symptoms typical of MRFV infection for all mutants tested. Furthermore, corn leafhoppers (Dalbulus maidis) transmitted the virus mutants to healthy plants at a frequency similar to that for wild-type MRFV US. Viral RNA recovered from plants infected with mutants both prior to and after leafhopper transmission retained mutations blocking ORF43 expression. The results indicate that ORF43 of MRFV is dispensable for both systemic infection of maize and transmission by leafhoppers. PMID- 26837894 TI - Enterovirus 71 transmission by exosomes establishes a productive infection in human neuroblastoma cells. AB - Exosomes are small secreted cellular vesicles for intercellular communications which contain proteins, mRNAs, and microRNAs (miRNAs). Recent studies have shown that exosomes play an important role in the transmission of infectious agents including hepatitis C virus, human immunodeficiency virus, and so on. However, the role of exosomes in the transfer of enterovirus 71 (EV71) between host cells remains unknown. In this study, we show that the exosomes derived from EV71 infected rhabdomyosarcoma cells contain EV71 RNA and capsid protein VP1, determined by quantitative reverse transcription-PCR (QRT-PCR) and Western blot analysis. The shedding of exosomes containing virus can establish a productive infection in human neuroblastoma cell line (SK-N-SH). A comparative analysis of neutralization by EV71-specific immunoglobulins showed different levels of neutralization of exosomes-mediated infection compared with free virus. In conclusion, exosomes from EV71-infected cells may play an important role in virus dissemination and are partially resisted to antibody neutralization. Our results suggest that there is an exosomal route of EV71 transmission infection. PMID- 26837895 TI - Enhanced humoral and cellular immune responses to PRRS virus GP5 glycoprotein by DNA prime-adenovirus boost vaccination in mice. AB - In order to investigate the induction of humoral and cellular immune responses against porcine reproductive and respiratory syndrome virus (PRRSV), BALB/c mice were immunized in a pcDNA3-GP5 prime-rAd-GP5 boost regimen. After humoral and cellular immune response detection, levels of PRRSV-specific antibodies, neutralizing antibodies, lymphocyte proliferation response, and cytotoxic T lymphocyte response were significantly increased as compared to controls. The humoral immune response was induced more effectively by the DNA priming and recombinant adenovirus boosting regimen. Significant difference was observed between heterogeneous and homologous vaccination. Induction of anti-GP5 antibody response was higher in all heterogeneous combinations than those of the homologous combinations. In the induction of lymphocyte proliferation response and CTL response, the homologous combination of pcDNA3-GP5/pcDNA3-GP5/pcDNA3 GP5was significantly stronger than that of rAd-GP5/rAd-GP5/rAd-GP5, but was relatively weaker than the heterogeneous combination of pcDNA3-GP5/pcDNA3-GP5/rAd GP5 and pcDNA3-GP5/rAd-GP5/rAd-GP5. This heterogeneous combination was a most efficient immunization regimen in induction of PRRSV-specific cellular immune response just as the antibody response. These results suggested that DNA immunization followed by recombinant adenovirus boosting could be used as a potential PRRSV vaccine. PMID- 26837897 TI - Temperature-dependent gel-type ionic liquid compounds based on vanadium substituted polyoxometalates with Keggin structure. AB - A series of temperature-dependent gel-type ionic liquid compounds have been synthesized from 1-(3-sulfonic group) propyl-3-methyl imidazolium (abbreviated as MIMPS) and three vanadium-substituted heteropoly acids H5SiW11VO40, H5SiMo11VO40 and H7SiW9V3O40. The designed and synthesized gel-type polyoxometalate ionic liquids (POM-ILs) have demonstrated a tendency to exhibit a layered structure. Moreover, they can undergo a phase transformation from a viscous gel-state to a liquid-state below 100 degrees C, and ionic conductivity up to 10(-3) S cm(-1) was observed at 120 degrees C. Cyclic voltammetry was carried out to study their electrochemical properties in organic solutions, and it was found that the oxidizability of the three POM-ILs decreases in the order: [MIMPS]7SiW9V3O40 > [MIMPS]5SiMo11VO40 > [MIMPS]5SiW11VO40. This result indicates that the redox behavior can be tuned by changing the chemical composition of the heteropolyanions. PMID- 26837898 TI - The Suicide Paradigm: Insights from Ancient Hindu Scriptures. AB - The world religions in general promote peace and happiness. They strongly discourage all sorts of violence in society including suicide. Religious commitments toward life-saving value are known to prevent suicide attempts since all world religions promote unity, reducing interpersonal hostilities. Therefore, understanding the basics on what religious scriptures narrate on life and death including suicide is essential. This paper highlights the seldom discussed topic on the concept and consequences of suicide portrayed in the ancient Hindu religious scriptures. PMID- 26837896 TI - Immunogenicity of transmissible gastroenteritis virus (TGEV) M gene delivered by attenuated Salmonella typhimurium in mice. AB - Attenuated Salmonella typhimurium (S. typhimurium) was selected as a transgenic vehicle for the development of live mucosal vaccines against transmissible gastroenteritis virus (TGEV) based on the M gene. An approximate 1.0 kb DNA fragment, encoding for glycoprotein M, was amplified by RT-PCR and cloned into eukaryotic expression vector pVAX1. The recombinant plasmid pVAX-M was transformed by electroporation into attenuated S. typhimurium SL7207, and the expression and translation of the pVAX-M delivered by recombinant S. typhimurium SL7207 (pVAX-M) was detected both in vitro and in vivo. BALB/c mice were inoculated orally with SL7207 (pVAX-M) at different dosages to evaluate safety of the vaccines. The bacterium was safe to mice at a dosage of 2 * 10(9) CFU, almost eliminated from the spleen and liver at week 4 post-immunization and eventually cleared at week 6. Mice immunized with 1 * 10(9) CFU of SL7207 (pVAX-M) elicited specific anti-TGEV local mucosal and humoral responses including levels of IgA, IgG, IL-4, and IFN-gamma as measured by indirect ELISA assay. Moreover, the control groups (pVAX group, PBS group) maintained at a normal level during week 4 8 post-immunization. The results indicated that attenuated S. typhimurium could be used as a delivery vector for oral immunization of TGEV M gene vaccine. PMID- 26837899 TI - Role of cardiac dyssynchrony and resynchronization therapy in functional mitral regurgitation. AB - Functional mitral regurgitation (FMR) is a common complication of left ventricle (LV) dysfunction and remodelling. Recently, it has been recognized as an independent prognostic factor in both ischaemic and non-ischaemic LV dysfunctions. In this review article, we discuss the mechanisms through which cardiac dyssynchrony is involved in FMR pathophysiologic cascade and how cardiac resynchronization therapy (CRT) can have therapeutic effects on FMR by reverting specific dyssynchrony pathways. We analyse recent clinical trials focusing on CRT impact on FMR in 'real-world' patients, the limits and future perspectives that could eventually generate new predictors of CRT response in terms of FMR reduction. Finally, we propose a practical diagnostic and therapeutic strategy for the management of symptomatic patients with severe LV dysfunction and concomitant 'prognostic' FMR. PMID- 26837901 TI - Benign Mimickers of Prostate Adenocarcinoma on Needle Biopsy and Transurethral Resection. AB - Prostate needle biopsy currently is the gold standard method for the diagnosis, management, and prognosis of prostate cancer. Obtaining an accurate diagnosis is crucial for pursuing proper patient management. This article discusses histologic mimickers of prostate carcinoma highlighting microscopic features that are helpful to reach a correct diagnosis and emphasizing potential diagnostic pitfalls. PMID- 26837900 TI - Understanding the host-adapted state of Citrobacter rodentium by transcriptomic analysis. AB - Citrobacter rodentium (Cr) is a mouse pathogen that mimics many aspects of enteropathogenic Escherichia coli infections including producing attaching and effacing (A/E) lesions. Host-adapted (HA) Cr cells that are shed at the peak of infection have been reported to be hyper-infective. The exact mechanism underlying this phenomenon has remained elusive since the pathogen loses its HA 'status' immediately upon subculturing in laboratory media. We sequenced the entire transcriptome of Cr directly from the feces of infected mice and analyzed the gene expression pattern. We observed that the entire transcriptional machinery as well as several transcriptional regulators to be differentially expressed when compared with the transcriptome of cells grown on laboratory media. Major adhesion and effector genes, tir and eae, were highly expressed in HA along with many genes located on all five loci of enterocyte effacement regions (LEE 1-5). Notable absent among the HA expressed genes were 19 fimbrial operons and non-fimbrial adhesions and several non-LEE encoded effectors. These results demonstrate that host-adapted Cr has a unique transcriptome that is associated with increased host transmission. PMID- 26837902 TI - Prostatic Adenocarcinoma, Prostatic Intraepithelial Neoplasia, and Intraductal Carcinoma. AB - Prostate carcinoma (PCa) exhibits a wide range of architectural and cytological features. Gleason grading remains as one of the most powerful histological prognostic parameters. However, it has evolved considerably. High-grade prostatic intraepithelial neoplasia (high-grade PIN) is accepted as a precursor lesion to PCa. Its detection in prostate biopsy is also considered as a risk factor for detecting cancer in subsequent biopsies. Such risk, however, has significantly decreased in recent studies. Intraductal carcinoma of the prostate (IDC-P) represents the intraductal spread of invasive cancer and constitutes a poor histologic parameter. This article reviews the key histological features of PCa, high-grade PIN and IDC-P, as well as the Gleason grading system that was most recently updated in 2005. PMID- 26837903 TI - Variants and Unusual Patterns of Prostate Cancer. AB - Beyond the typical acinar morphology observed in most prostatic adenocarcinoma, a spectrum of morphologic variants and prostate cancer subtypes exists. These unusual entities may be further classified into (1) cancer morphologies arising by divergent differentiation of prostatic ductal, acinar, or basal cells and associated with unique clinical features or therapeutic approaches, and (2) histologies occurring in the context of usual prostatic adenocarcinoma that may result in diagnostic misinterpretation or difficulties in Gleason grade assignment, especially in limited samples. This article details several variants, with emphasis on diagnostic criteria, differential diagnoses, and clinical significance. PMID- 26837904 TI - Mesenchymal Tumors of the Prostate. AB - Prostatic mesenchymal tumors encompass various benign and malignant neoplasms that may derived from the intrinsic prostatic stroma or from associated elements including muscle, connective tissue, blood vessels, and neural structures. The differential diagnosis of these tumors is broad and encompasses prostatic epithelial processes that demonstrate prominent spindle cell morphology, as well as mesenchymal tumors that secondarily involve the prostate. Careful morphologic examination, clinical history, and judicious use of a limited panel of immunohistochemical markers and molecular tests aid in the proper diagnosis of these lesions. This article provides a structured guide for the analysis and diagnosis of both benign and malignant prostatic mesenchymal lesions and highlights key features that distinguish these entities within the differential diagnosis of prostatic spindle cell lesions. PMID- 26837905 TI - Benign Diseases of the Bladder. AB - Benign diseases of the bladder often present diagnostic challenges to practicing pathologists due to their diverse nature and ability to mimic a variety of epithelial or mesenchymal neoplasms. Categories of benign bladder disease include infectious cystitis, noninfectious cystitis, reactive proliferative processes, and benign processes that secondarily involve the bladder. An understanding of the key clinical and morphologic features of these lesions and the useful ancillary techniques specific for these entities is critical to the correct diagnosis of these lesions. This article reviews the key features of these benign bladder diseases and highlights methods to distinguish these lesions from other benign and malignant processes involving the bladder. PMID- 26837906 TI - Urothelial Carcinoma and its Variants. AB - Bladder cancer is the ninth most common cancer worldwide, and the most common malignancy affecting the urinary tract, with approximately 330,000 new cases and more than 130,000 deaths per year. Bladder cancer is primarily attributable to smoking, which accounts for 65% of male and 30% of female cases in some developed countries. Other major risk factors include analgesic abuse, some types of chemotherapy, occupational exposure to chemicals, and in Egypt and some Asian regions, endemic infection with Schistosoma haematobium. Approximately 90% of bladder tumors are classified as urothelial carcinoma (UC), also referred to as transitional cell carcinoma (TCC), and are believed to originate from transformation of the normal urothelium. UCs often exhibit elements of squamous or glandular differentiation. The spectrum of microscopic forms of urothelial carcinoma has been expanded recently to include several histologic variants, the recognition of which is important to avoid diagnostic misinterpretation, to predict outcome, and to guide the selection of the most appropriate therapeutic approach. This article reviews characteristic pathologic features and key clinical aspects of UC and its most common variants. PMID- 26837907 TI - Molecular Pathology of the Genitourinary Tract: Prostate and Bladder. AB - The knowledge of cellular mechanisms in tumors of the prostate and bladder has grown exponentially. Molecular technologies have led to the discovery of TMPRSS2 in prostate cancer and the molecular pathways distinguishing low- and high-grade urothelial neoplasms. UroVysion with fluorescence in situ hybridization is already commonplace as an adjunct to cytologic diagnosis of urothelial neoplasms. This trend portends the future in which classification and diagnosis of tumors of the prostate and bladder through morphologic analysis will be supplemented by molecular information correlating with prognosis and targeted therapy. This article outlines tumor molecular pathology of the prostate and bladder encompassing current genomic, epigenomic, and proteonomic findings. PMID- 26837908 TI - Foreword. PMID- 26837909 TI - Preface. PMID- 26837911 TI - Electric Control of the Hall effect in Pt/Bi0.9La0.1FeO3 bilayers. AB - Platinum metal, being nonmagnetic and with a strong spin-orbit coupling interaction, has been deposited on weak ferromagnetic Bi0.9La0.1FeO3 thin films. The Hall effect is studied as a function of the polarization direction of multiferroic Bi0.9La0.1FeO3 thin films, as well as magnetic field (H) and temperature (T). For the two polarization directions, besides the obvious difference of the anomalous Hall resistance RAH, it increases sharply with decreasing temperature, and even changes sign, thus violating the conventional expression. This observations indicate local magnetic moments in Pt caused by the local electric fields at the interface of Bi0.9La0.1FeO3 films. Also, possible proximity effects and induced magnetic ordering in Pt on weak ferromagnetic Bi0.9La0.1FeO3 thin films of both upward and downward polarization states may exist and their contribution to the spin-related measurements should not be neglected. PMID- 26837913 TI - Bone Tumor Radiology 101 for Pathologists. AB - This review discusses how certain imaging features of bone tumors can give valuable clues as to their histology. The author emphasizes the clinical presentation of the patient, and how close cooperation among the radiologist, pathologist, and orthopedic surgeon are paramount in achieving an accurate diagnosis of bone tumors as well as optimizing their management. PMID- 26837912 TI - Template-Stripped Multifunctional Wedge and Pyramid Arrays for Magnetic Nanofocusing and Optical Sensing. AB - We present large-scale reproducible fabrication of multifunctional ultrasharp metallic structures on planar substrates with capabilities including magnetic field nanofocusing and plasmonic sensing. Objects with sharp tips such as wedges and pyramids made with noble metals have been extensively used for enhancing local electric fields via the lightning-rod effect or plasmonic nanofocusing. However, analogous nanofocusing of magnetic fields using sharp tips made with magnetic materials has not been widely realized. Reproducible fabrication of sharp tips with magnetic as well as noble metal layers on planar substrates can enable straightforward application of their material and shape-derived functionalities. We use a template-stripping method to produce plasmonic-shell coated nickel wedge and pyramid arrays at the wafer-scale with tip radius of curvature close to 10 nm. We further explore the magnetic nanofocusing capabilities of these ultrasharp substrates, deriving analytical formulas and comparing the results with computer simulations. These structures exhibit nanoscale spatial control over the trapping of magnetic microbeads and nanoparticles in solution. Additionally, enhanced optical sensing of analytes by these plasmonic-shell-coated substrates is demonstrated using surface-enhanced Raman spectroscopy. These methods can guide the design and fabrication of novel devices with applications including nanoparticle manipulation, biosensing, and magnetoplasmonics. PMID- 26837914 TI - Arthritis Pathology. AB - The pathologic examination of failed joints, whether natural or artificial, is an indispensable part of the understanding of arthritis, as it is the last, and still best opportunity to determine or verify the correct diagnosis. Accuracy in pathologic diagnosis, based on a firm understanding of the various disease processes, provides reliable data for use in clinical registries, provides an opportunity to explain the "unusual" clinical presentation, and ultimately gives the "best evidence" for basing further treatments and prognosis for the individual patient. PMID- 26837915 TI - The Role of the Pathologist in Diagnosing Periprosthetic Infection. AB - Most patients who undergo total joint arthroplasty experience dramatic relief of pain and improved ambulation for many years, but some eventually develop pain, often accompanied by radiographic evidence of bone resorption around their implants. The most frequent cause of device failure is osteolysis, but infection is another important cause of pain and arthroplasty failure. The distinction between infection and aseptic loosening is important because the 2 conditions are treated very differently. The purpose of this article is to summarize the role of the anatomic and clinical pathologist in helping distinguish aseptic loosening from infection. PMID- 26837916 TI - Bone Cytology: A Realistic Approach for Clinical Use. AB - This article presents the use of bone cytology for diagnosis of bone tumors. It discusses critical factors and considerations of fine-needle aspiration and bone cytology and presents diagnostic options and differential diagnosis for benign and malignant bone lesions. Osteomyelitis, chrondroblastoma, Langerhans cell histiocytosis, chondromyxoid fibromas, enchondromas, giant cell tumor of bone, osteosarcoma, chondrosarcoma and variants, Ewing sarcoma, chordoma, plasmacytoma, multiple myeloma, lymphoma, and metastatic bone disease are presented. PMID- 26837917 TI - Benign Bone-Forming Tumors: Approach to Diagnosis and Current Understanding of Pathogenesis. AB - The diagnosis of benign bone-forming tumors continues to be based on the traditional approach to bone tumor diagnosis using knowledge of the spectrum of histopathologic features seen in these tumors in combination with clinical and radiological correlation. This review emphasizes the pathologic features and the clinical and radiological features that the surgical pathologist must have a working understanding of to make an accurate diagnosis and avoid confusion with other lesions, particularly osteosarcoma. New and persistent challenges facing the practicing pathologist and our current understanding of the cytogenetic and molecular abnormalities involved in the pathogenesis of these tumors are discussed. PMID- 26837918 TI - Osteosarcoma: Differential Diagnostic Considerations. AB - Accurate diagnosis of bone-forming tumors, including correct subclassification of osteogenic sarcoma is critical for determination of appropriate clinical management and prediction of patient outcome. The morphologic spectrum of osteogenic sarcoma is extensive, however, and its histologic mimics are numerous. This review focuses on the major differential diagnoses of the specific subtypes of osteosarcoma, presents summaries of various diagnoses, and provides tips to overcoming pitfalls in diagnosis. PMID- 26837919 TI - Well-Differentiated Central Cartilage Tumors of Bone: An Overview. AB - Well-differentiated hyaline cartilage tumors are among the most common tumors encountered in the skeleton; their radiographic and pathologic classification and clinical management can be challenging. Pathologists find cartilage tumors difficult because their precise classification is as dependent on the clinical and radiographic findings as the histologic features; the distinction between benign and malignant cartilage neoplasms demands good communication and teamwork between pathologists, orthopedic surgeons, and radiologists. This review focuses on the necessary clinical, radiographic, and pathologic features that allow distinction between enchondroma and low-grade central chondrosarcoma and interpretation of lesions encountered in the enchondromatosis syndromes. PMID- 26837920 TI - Chondrosarcoma Variants. AB - This article presents a review of chondrosarcoma variants, with a focus on the extraordinarily rare variants of chondrosarcoma in which hyaline cartilage is not the dominant feature. Discussed are the differential diagnoses for these neoplasms, radiologic studies, gross and microscopic features, and prognosis. Summaries are provided of the key features for the major variants. PMID- 26837921 TI - Giant Cell Tumor of Bone. AB - This article provides an overview of giant cell tumor, including the typical clinical, radiographic, and pathologic findings, as well as some unusual features, such as multifocality and metastases. The article addresses recent advances in the molecular biology of giant cell tumor, particularly receptor activator of nuclear factor kappa B (RANK)-ligand signaling, in addition to novel anti-RANK-ligand therapy, the use of which seems promising for unresectable and metastatic tumors. PMID- 26837923 TI - Small Round Cell Tumors of Bone. AB - Diagnosing small round cell tumors (SCRTs) can be a difficult task for pathologists due to overlapping clinicopathologic features. This review highlights the clinical, radiographic, histologic, immunohistochemical, and genetic features of the most common SRCTs involving bone with an emphasis on differential diagnosis. SRCTs are a heterogeneous group of neoplasms characterized by poorly differentiated cells with small, blue, round nuclei and scant cytoplasm. They can occur as primary tumors in bone or soft tissue. PMID- 26837922 TI - Fibro-Osseous Lesions. AB - This article describes the clinical, radiographic, gross, microscopic, and histologic features; differential diagnosis; molecular pathology; treatment; and prognosis of fibrous dysplasia, osteofibrous dysplasia, and adamantinoma of long bones. PMID- 26837924 TI - Pseudotumors and Reactive Lesions. AB - This article discusses reactive or degenerative processes in bone or periosteal soft tissue that occasionally masquerade as neoplasms. Presentation of the clinical, radiologic, and pathologic features of these processes is provided with an emphasis on the avoidance of overdiagnosis. Clinical, radiologic, and pathologic features of pseudotumors are presented in detail. This article approaches these tumor-like lesions in 2 categories: (1) those in the soft tissue next to bone and (2) those inside bones from the aspect of mineralization and calcification. PMID- 26837925 TI - Skeletal Metastasis. AB - The most commonly diagnosed tumor in the skeleton represents metastatic disease. Metastatic carcinoma should be the first consideration in older patients with atypical radiologic findings or clinical features suggestive of a bone lesion. The primary goal in the setting of skeletal metastasis is usually palliation. PMID- 26837926 TI - Bone Pathology: Pathology, Radiology, and Orthopedics. PMID- 26837928 TI - A Video Analysis of Use of the New 'Concussion Interchange Rule' in the National Rugby League. AB - The National Rugby League (NRL) in Australia introduced a new 'concussion interchange rule' (CIR) in 2014, whereby a player suspected of having sustained a concussion can be removed from play, and assessed, without an interchange being tallied against the player's team. We conducted a video analysis, describing player and injury characteristics, situational factors, concussion signs, and return to play for each "CIR" event for the 2014 season. There were 167 reported uses of the CIR. Apparent loss of consciousness/unresponsiveness was observed in 32% of cases, loss of muscle tone in 54%, clutching the head in 70%, unsteadiness of gait in 66%, and a vacant stare in 66%. More than half of the players who were removed under the CIR returned to play later in the same match (57%). Most incidences occurred from a hit up (62%) and occurred during a tackle where the initial contact was with the upper body (80%). The new concussion interchange rule has been used frequently during the first season of its implementation. In many cases, there appeared to be video evidence of injury but the athlete was cleared to return to play. More research is needed on the usefulness of video review for identifying signs of concussive injury. PMID- 26837929 TI - Metabolic Differences Between Shod and Barefoot Walking in Children. AB - Footwear affects the biomechanics of children's gait; however, there has been less research addressing the energetics of walking with and without shoes. This study investigated the effects of barefoot and shod walking on metabolic parameters in children. 25 children (9.7+/-1.4 years) walked at a self-selected pace for 5 min on an instrumented treadmill under 2 footwear conditions (barefoot, running shoe). Vertical oscillations of centre of mass were calculated from ground reaction forces. Expired gases were collected in the last minute of each trial. Paired t-tests revealed significantly higher oxygen consumption (17.6+/-2.5 ml.kg(-1).min(-1) vs. 16.3+/-3.1 ml.kg(-1).min(-1)), energy expenditure (3.25+/-0.86 kcal.min(-1) vs. 2.97+/-0.68 kcal.min(-1)), and economy (298.2+/-47.5 ml.kg(-1).km(-1) vs. 275.9+/-56.9 ml.kg(-1).km(-1)) during the shod condition. There was no difference in substrate utilization between conditions. The barefoot condition elicited a smaller centre of mass vertical displacement (1.24+/-0.14 cm vs. 1.34+/-0.17 cm). At a natural walking speed, barefoot walking is more economical than shod walking at the same velocity in children. The higher energy cost of shod walking should be considered when evaluating the use of footwear by children. PMID- 26837930 TI - CNTFR Genotype and Sprint/power Performance: Case-control Association and Functional Studies. AB - The aim of this study was to investigate whether rs41274853 in the 3' untranslated region of the ciliary neurotrophic factor receptor gene (CNTFR) is associated with elite sprint/power athletic status and assess its functional significance. A total of 211 Japanese sprint/power track and field athletes (62 international, 72 national, and 77 regional athletes) and 814 Japanese controls were genotyped at rs41274853. Luciferase reporter assay was conducted to investigate whether this C-to-T polymorphism affects binding of microRNA miR-675 5p to this region. The TT genotype was significantly more frequent among international sprint/power athletes (19.4%) than in the controls after Bonferroni correction (7.9%, P=0.036, OR=2.81 [95% CI: 1.43-5.55]). Furthermore, in non athletic young/middle-aged men (n=132), TT genotype carriers exhibited significantly greater leg extension power (26.6+/-5.4 vs. 24.0+/-5.4 W/kg BW, P=0.019) and vertical jump performance (50.1+/-6.9 vs. 47.9+/-7.5 cm, P=0.047) than the CC+CT genotype carriers. Reporter assays revealed that the miR-675-5p binds to this polymorphic region within the CNTFR mRNA, irrespective of the rs41274853 allele present. Although the functional significance of the rs41274853 polymorphism remains unclear, the CNTFR is one of the candidate genes contributing to sprint/power performance. PMID- 26837932 TI - An Acute Bout of Barefoot Running Alters Lower-limb Muscle Activation for Minimalist Shoe Users. AB - Despite the abundance of barefoot running-related research, there have been no electromyography studies evaluating the effects of this mode of exercise on habitual users of minimalist footwear. The present study investigated differences in muscle activation during acute bouts of barefoot and shod running, in minimalist shoe users. 8 male participants ran on a motorized treadmill for 10 min under both conditions, at 70% maximal aerobic speed. Electromyographic data were sampled from the biceps femoris, gluteus maximus, gastrocnemius medialis, tibialis anterior, and vastus lateralis during both swing and stance. Root-mean square analysis of electromyographic data was conducted to compare muscle activation between conditions. During stance, barefoot running resulted in greater muscle activity in gastrocnemius medialis and gluteus maximus, and lower muscle activity in tibialis anterior. During swing, barefoot running resulted in increased muscle activity in vastus lateralis and gastrocnemius medialus. These results indicate that, for minimalist shoe users, an acute bout of barefoot running results in significantly different lower-limb muscle activity. Increased activation in the above muscles presents a possible mechanism for injury, which should be considered during exercise prescription. PMID- 26837931 TI - Leukocyte Responsiveness to Exercise in Individuals Positive for Human Cytomegalovirus. AB - Human cytomegalovirus (HCMV) infects 50% of adults in the United States. HCMV can become a cause for concern in individuals who have a compromised immune system, which may occur after high-intensity exercise. The purpose of this preliminary study was to characterize the lymphocyte, monocyte, and neutrophil responses to exercise in HCMV+individuals. Participants were either positive (HCMV +) or negative (HCMV-) for HCMV. Participants visited the laboratory on 3 separate occasions: HCMV screening, 100% VO2max test, and 80% VO2max run. Mixed-model factorial ANOVA procedures with repeated measures on sampling condition were performed on absolute and relative circulating lymphocytes, monocytes, and neutrophils. Significant main effects for time for both absolute and relative values were seen for all leukocyte subsets regardless of virus status. Significant differences for absolute and relative values were seen between sampling conditions for all leukocyte subsets. We report for the first time that HCMV status does not affect circulating neutrophil responses to high-intensity exercise, though exercise-induced neutrocytosis is seen during the post-exercise and 60 min post-exercise sampling conditions, regardless of HCMV status. There is no HCMV effect on circulating monocyte responses to exercise, though exercise induced monocytosis was seen during the post-exercise sampling condition regardless of HCMV status. PMID- 26837927 TI - Aquaporin-5: from structure to function and dysfunction in cancer. AB - Aquaporins, a highly conserved group of membrane proteins, are involved in the bidirectional transfer of water and small solutes across cell membranes taking part in many biological functions all over the human body. In view of the wide range of cancer malignancies in which aquaporin-5 (AQP5) has been detected, an increasing interest in its implication in carcinogenesis has emerged. Recent publications suggest that this isoform may enhance cancer cell proliferation, migration and survival in a variety of malignancies, with strong evidences pointing to AQP5 as a promising drug target and as a novel biomarker for cancer aggressiveness with high translational potential for therapeutics and diagnostics. This review addresses the structural and functional features of AQP5, detailing its tissue distribution and functions in human body, its expression pattern in a variety of tumors, and highlighting the underlying mechanisms involved in carcinogenesis. Finally, the actual progress of AQP5 research, implications in cancer biology and potential for cancer detection and prognosis are discussed. PMID- 26837933 TI - Impact Accelerations of Barefoot and Shod Running. AB - During the ground contact phase of running, the body's mass is rapidly decelerated resulting in forces that propagate through the musculoskeletal system. The repetitive attenuation of these impact forces is thought to contribute to overuse injuries. Modern running shoes are designed to reduce impact forces, with the goal to minimize running related overuse injuries. Additionally, the fore/mid foot strike pattern that is adopted by most individuals when running barefoot may reduce impact force transmission. The aim of the present study was to compare the effects of the barefoot running form (fore/mid foot strike & decreased stride length) and running shoes on running kinetics and impact accelerations. 10 healthy, physically active, heel strike runners ran in 3 conditions: shod, barefoot and barefoot while heel striking, during which 3-dimensional motion analysis, ground reaction force and accelerometer data were collected. Shod running was associated with increased ground reaction force and impact peak magnitudes, but decreased impact accelerations, suggesting that the midsole of running shoes helps to attenuate impact forces. Barefoot running exhibited a similar decrease in impact accelerations, as well as decreased impact peak magnitude, which appears to be due to a decrease in stride length and/or a more plantarflexed position at ground contact. PMID- 26837935 TI - Critical appraisal of selegiline transdermal system for major depressive disorder. AB - INTRODUCTION: Although safer and easier to use antidepressants (ie.,SSRIs/SNRIs) have largely displaced MAOIs, these medications still have a role in difficult to treat conditions. Efforts to improve MAOIs benefit-risk profile resulted on the reversible MAOI and in the first antidepressant patch (selegiline transdermal delivery system-STS). The later had been available in the US since 2006. Thus a review on its safety profile and comparative efficacy is timely. AREAS COVERED: This review provides an overview of STS's clinical pharmacology and summarizes what has been learned across nearly a decade of experience. Product labels and the search engine PubMed were used to obtain relevant information. EXPERT OPINION: STS remains a unique treatment option. It is the only FDA-approved antidepressant for patients with significant problems ingesting, tolerating, or absorbing oral medications. It remains the only MAOI that can be initiated without dietary restrictions at a therapeutic dose and has a low incidence of side effects when compared to other MAOIs. STS also provides an interesting option for depressed patients suffering from Parkinson's disease. However these advantages are counterweighted by drawbacks including the need for wash-out periods and the lack of convincing data illustrating its utility for treatment of more severe, treatment refractory depression. PMID- 26837936 TI - Inherent predominance of high chiral angle metallic carbon nanotubes in continuous fibers grown from a molten catalyst. AB - We present evidence that high temperature CVD growth of SWNTs under conditions of continuous spinning of macroscopic fibers leads to an inherent predominance of high chiral angle CNTs, peaking at the armchair end. Raman, UV-vis-NIR absorption, and photoluminescence spectroscopy measurements show the prevalence of metallic SWNTs. The complete chiral angle distribution is obtained by electron diffraction of over 390 CNTs. It is biased towards high chiral angles and peaks at the armchair end (30 degrees ), in good agreement with the established atomistic models for SWNT growth from a liquid catalyst. Based on the Fe-C-S constituent binary and ternary phase diagrams, thermodynamic calculations of phase compositions from fast cooling and experimental evidence of a post synthesis catalyst, the proposed thermodynamic path of the catalyst is to form a solid FCC Fe core and a liquid Fe-S shell. S in the outer liquid shell first stabilizes the edge of the nascent CNT, but once a graphitic wall forms it is rejected due to the high interfacial energy of the Fe-C-S alloy. PMID- 26837934 TI - Cardiorespiratory Fitness and Metabolic Syndrome in Postmenopausal African American Women. AB - We examined the association of cardiorespiratory fitness with metabolic syndrome in overweight/obese postmenopausal African-American women. Pooled baseline data on 170 African-American women from 2 exercise trials were examined. Metabolic syndrome was defined as at least 3 of the following: abdominal obesity, glucose intolerance, hypertension, low high-density lipoprotein cholesterol (HDL-C), and high triglycerides. Cardiorespiratory fitness (VO2peak) was determined using the Bruce treadmill protocol and categorized as: Very Low (VLCRF<18 mL.kg(-1) min( 1)), Low (LCRF=18.0-220-22-22.0 mL.kg(-1) min(-1)), and Moderate (MCRF>22.0 mL.kg(-1) min(-1)). Associations of metabolic syndrome with cardiorespiratory fitness were analyzed using one-way ANOVA and linear regression. VO2peak was significantly lower in the VLCRF compared to the MCRF group. Lower cardiorespiratory fitness was associated with higher prevalence of metabolic syndrome, abdominal obesity, hypertriglyceridemia, and low HDL among overweight/obese postmenopausal African-American women. In fully adjusted models, higher waist circumference and triglycerides were associated with lower VO2peak levels (P<0.01) and higher HDL-C was associated with higher VO2peak levels (P=0.03). Overweight/obese postmenopausal African-American women with very low cardiorespiratory fitness are more likely to have metabolic syndrome, higher body mass index, and unhealthier levels of certain metabolic syndrome components than women with moderate cardiorespiratory fitness. PMID- 26837937 TI - A scoping review of competencies for scientific editors of biomedical journals. AB - BACKGROUND: Biomedical journals are the main route for disseminating the results of health-related research. Despite this, their editors operate largely without formal training or certification. To our knowledge, no body of literature systematically identifying core competencies for scientific editors of biomedical journals exists. Therefore, we aimed to conduct a scoping review to determine what is known on the competency requirements for scientific editors of biomedical journals. METHODS: We searched the MEDLINE(r), Cochrane Library, Embase(r), CINAHL, PsycINFO, and ERIC databases (from inception to November 2014) and conducted a grey literature search for research and non-research articles with competency-related statements (i.e. competencies, knowledge, skills, behaviors, and tasks) pertaining to the role of scientific editors of peer-reviewed health related journals. We also conducted an environmental scan, searched the results of a previous environmental scan, and searched the websites of existing networks, major biomedical journal publishers, and organizations that offer resources for editors. RESULTS: A total of 225 full-text publications were included, 25 of which were research articles. We extracted a total of 1,566 statements possibly related to core competencies for scientific editors of biomedical journals from these publications. We then collated overlapping or duplicate statements which produced a list of 203 unique statements. Finally, we grouped these statements into seven emergent themes: (1) dealing with authors, (2) dealing with peer reviewers, (3) journal publishing, (4) journal promotion, (5) editing, (6) ethics and integrity, and (7) qualities and characteristics of editors. DISCUSSION: To our knowledge, this scoping review is the first attempt to systematically identify possible competencies of editors. Limitations are that (1) we may not have captured all aspects of a biomedical editor's work in our searches, (2) removing redundant and overlapping items may have led to the elimination of some nuances between items, (3) restricting to certain databases, and only French and English publications, may have excluded relevant publications, and (4) some statements may not necessarily be competencies. CONCLUSION: This scoping review is the first step of a program to develop a minimum set of core competencies for scientific editors of biomedical journals which will be followed by a training needs assessment, a Delphi exercise, and a consensus meeting. PMID- 26837938 TI - Buffering agents modify the hydration landscape at charged interfaces. AB - Buffering agents are widely used to stabilise the pH of solutions in soft matter and biological sciences. They are typically composed of weak acids and bases mixed in an aqueous solution, and can interact electrostatically with charged surfaces such as biomembranes. Buffers can induce protein aggregation and structural modification of soft interfaces, but a molecular-level picture is still lacking. Here we use high-resolution atomic force microscopy to investigate the effect of five commonly used buffers, namely 4-(2-hydroxyethyl)piperazine-1 ethanesulfonic acid (HEPES), 2-(N-morpholino)ethanesulfonic acid (MES), monosodium phosphate, saline sodium citrate (SSC) and tris(hydroxymethyl)aminomethane (Tris) on the hydration landscape of Muscovite mica in solution. Mica is an ideal model substrate due to its negative surface charge and identical lattice parameter when compared with gel-phase lipid bilayers. We show that buffer molecules can produce cohesive aggregates spanning over tens of nanometres of the interface. SSC, Tris and monosodium phosphate tend to create an amorphous mesh layer several molecules thick and with no preferential ordering. In contrast, MES and HEPES adopt epitaxial arrangements commensurate with the underlying mica lattice, suggesting that they offer the most suitable solution for high-resolution studies. To confirm that this effect persisted in biologically-relevant interfaces, the experiments were repeated on a silica-supported lipid bilayer. Similar trends were observed for this system using atomic force microscopy as well as ellipsometry. The effect of the buffering agents can be mitigated by the inclusion of salt which helps displace them from the interface. PMID- 26837939 TI - Successful treatment of Sydenham's chorea with intravenous immunoglobulin. AB - We present a case of a 10-year-old girl diagnosed with Sydenham's chorea. Despite treatment with haloperidol and valproic acid for 2 weeks and antibiotics for 5 days, her symptoms continued to worsen. She became severely impaired in daily functioning, as she could barely speak or walk, experienced major feeding difficulties and required help with all daily activities. She was treated with intravenous immunoglobulin (IVIG). Within 4 days, her symptoms started to improve and after 1-month she had fully recovered. This case reminds us that Sydenham's chorea can result in major functional impairment. There is some evidence on the beneficial effect of IVIG in the treatment of Sydenham's chorea, as is evident in our case. Therefore, IVIG should be considered as a treatment option in patients with severe chorea. PMID- 26837940 TI - Behcet's syndrome with gangrenous bilateral lower limbs. PMID- 26837941 TI - Simultaneous dislocation of both the proximal and distal interphalangeal joints of a little finger. AB - A 39-year-old man fell at work sustaining dislocation of both the proximal and distal interphalangeal joints of his left little finger. The injuries were assessed and treated with closed reduction and stabilised by buddy taping. Early active range of movement was encouraged and a referral to physiotherapy was made. At the final follow-up, 4 months after the injury, he lacked subtle end of range movement actively, but functionally he was coping well and had made a full return to work. PMID- 26837942 TI - Rare extrapulmonary complications of Mycoplasma pneumoniae infection. AB - Stevens-Johnsons syndrome (SJS) is a rare extra-pulmonary complication of Mycoplasma pneumoniae infection. We present the case of a 26-year-old man with fever, cough, extensive oral mucosal ulceration and a widespread truncal rash. He was diagnosed with M. pneumoniae-induced SJS. He responded well to antibiotics and steroids initially, but went on to develop pseudomembranous conjunctivitis requiring bilateral amniotic membrane grafting. SJS is most commonly drug induced, however, M. pneumoniae is the commonest infectious cause and should be considered in the differential diagnosis. It is also important to get specialist care involved early to minimise the long-term effects of any complications. PMID- 26837943 TI - Spontaneous rectus sheath haematoma secondary to severe coughing in a patient with no other precipitating factors. PMID- 26837946 TI - ERRATA. PMID- 26837945 TI - "Schizophrenia" does not exist. PMID- 26837944 TI - Betel quid dependence is associated with functional connectivity changes of the anterior cingulate cortex: a resting-state fMRI study. AB - OBJECTIVE: It is generally acknowledged that drug dependence is connected with abnormal functional organization in the individual's brain. The present study aimed to identify the anterior cingulate cortex (ACC) abnormality with the cerebral networks involved in betel quid dependence (BQD) by resting-state functional connectivity (rsFC) using functional magnetic resonance imaging (fMRI). METHODS: With fMRI data measured from 33 resting-state BQD individuals and 32 non-addicted and age-, sex-, education-matched healthy controls, we inquired into the BQD-related changes in FC between the regions of ACC with the whole brain involved in BQD individuals using a region of interest vised method, and to identify the relation of the alteration with the severity of BQD and duration. RESULTS: Compared to controls, the BQD group showed increased connectivity from ACC to the regions of the reward network (brainstem including midbrain regions such as the ventral tegmental area and pons, caudate, thalamus) and cerebellum. Decreased connectivity was observed in the BQD group in regions from ACC to the default mode network (medial prefrontal cortex and precuneus) and para Hippocampal/hypothalamus. Specifically, the BQD scale was positively correlated with increased FC of right ACC to left thalamus and left ACC to pons; the durations were negatively correlated with FC of right ACC to left precuneus. CONCLUSION: These disturbances in rsFC from ACC to the reward network and DMN revealed by fMRI may have a key function in providing insights into the neurological pathophysiology underlying BQD-associated executive dysfunction and disinhibition. These findings may contribute to our better understanding of the mechanisms underlying BQD. PMID- 26837948 TI - Sensory Neuronopathy in CANVAS: Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia. PMID- 26837955 TI - Dual emission in asymmetric "giant" PbS/CdS/CdS core/shell/shell quantum dots. AB - Semiconducting nanocrystals optically active in the infrared region of the electromagnetic spectrum enable exciting avenues in fundamental research and novel applications compatible with the infrared transparency windows of biosystems such as chemical and biological optical sensing, including nanoscale thermometry. In this context, quantum dots (QDs) with double color emission may represent ultra-accurate and self-calibrating nanosystems. We present the synthesis of giant core/shell/shell asymmetric QDs having a PbS/CdS zinc blende (Zb)/CdS wurtzite (Wz) structure with double color emission close to the near infrared (NIR) region. We show that the double emission depends on the excitation condition and analyze the electron-hole distribution responsible for the independent and simultaneous radiative exciton recombination in the PbS core and in the CdS Wz shell, respectively. These results highlight the importance of the driving force leading to preferential crystal growth in asymmetric QDs, and provide a pathway for the rational control of the synthesis of double color emitting giant QDs, leading to the effective exploitation of visible/NIR transparency windows. PMID- 26837953 TI - Genomic Access to Monarch Migration Using TALEN and CRISPR/Cas9-Mediated Targeted Mutagenesis. AB - The eastern North American monarch butterfly, Danaus plexippus, is an emerging model system to study the neural, molecular, and genetic basis of animal long distance migration and animal clockwork mechanisms. While genomic studies have provided new insight into migration-associated and circadian clock genes, the general lack of simple and versatile reverse-genetic methods has limited in vivo functional analysis of candidate genes in this species. Here, we report the establishment of highly efficient and heritable gene mutagenesis methods in the monarch butterfly using transcriptional activator-like effector nucleases (TALENs) and CRISPR-associated RNA-guided nuclease Cas9 (CRISPR/Cas9). Using two clock gene loci, cryptochrome 2 and clock (clk), as candidates, we show that both TALENs and CRISPR/Cas9 generate high-frequency nonhomologous end-joining (NHEJ) mediated mutations at targeted sites (up to 100%), and that injecting fewer than 100 eggs is sufficient to recover mutant progeny and generate monarch knockout lines in about 3 months. Our study also genetically defines monarch CLK as an essential component of the transcriptional activation complex of the circadian clock. The methods presented should not only greatly accelerate functional analyses of many aspects of monarch biology, but are also anticipated to facilitate the development of these tools in other nontraditional insect species as well as the development of homology-directed knock-ins. PMID- 26837952 TI - Utilizing Gene Tree Variation to Identify Candidate Effector Genes in Zymoseptoria tritici. AB - Zymoseptoria tritici is a host-specific, necrotrophic pathogen of wheat. Infection by Z. tritici is characterized by its extended latent period, which typically lasts 2 wks, and is followed by extensive host cell death, and rapid proliferation of fungal biomass. This work characterizes the level of genomic variation in 13 isolates, for which we have measured virulence on 11 wheat cultivars with differential resistance genes. Between the reference isolate, IPO323, and the 13 Australian isolates we identified over 800,000 single nucleotide polymorphisms, of which ~10% had an effect on the coding regions of the genome. Furthermore, we identified over 1700 probable presence/absence polymorphisms in genes across the Australian isolates using de novo assembly. Finally, we developed a gene tree sorting method that quickly identifies groups of isolates within a single gene alignment whose sequence haplotypes correspond with virulence scores on a single wheat cultivar. Using this method, we have identified < 100 candidate effector genes whose gene sequence correlates with virulence toward a wheat cultivar carrying a major resistance gene. PMID- 26837954 TI - Barcode Sequencing Screen Identifies SUB1 as a Regulator of Yeast Pheromone Inducible Genes. AB - The yeast pheromone response pathway serves as a valuable model of eukaryotic mitogen-activated protein kinase (MAPK) pathways, and transcription of their downstream targets. Here, we describe application of a screening method combining two technologies: fluorescence-activated cell sorting (FACS), and barcode analysis by sequencing (Bar-Seq). Using this screening method, and pFUS1-GFP as a reporter for MAPK pathway activation, we readily identified mutants in known mating pathway components. In this study, we also include a comprehensive analysis of the FUS1 induction properties of known mating pathway mutants by flow cytometry, featuring single cell analysis of each mutant population. We also characterized a new source of false positives resulting from the design of this screen. Additionally, we identified a deletion mutant, sub1Delta, with increased basal expression of pFUS1-GFP. Here, in the first ChIP-Seq of Sub1, our data shows that Sub1 binds to the promoters of about half the genes in the genome (tripling the 991 loci previously reported), including the promoters of several pheromone-inducible genes, some of which show an increase upon pheromone induction. Here, we also present the first RNA-Seq of a sub1Delta mutant; the majority of genes have no change in RNA, but, of the small subset that do, most show decreased expression, consistent with biochemical studies implicating Sub1 as a positive transcriptional regulator. The RNA-Seq data also show that certain pheromone-inducible genes are induced less in the sub1Delta mutant relative to the wild type, supporting a role for Sub1 in regulation of mating pathway genes. The sub1Delta mutant has increased basal levels of a small subset of other genes besides FUS1, including IMD2 and FIG1, a gene encoding an integral membrane protein necessary for efficient mating. PMID- 26837956 TI - Infectious Etiologies and Patient Outcomes in Pediatric Septic Shock. AB - Background: Septic shock remains an important cause of death and disability in children. Optimal care requires early recognition and treatment. Methods: We evaluated a retrospective cohort of children (age <19) treated in our emergency department (ED) for septic shock during 2008-2012 to investigate the association between timing of antibiotic therapy and outcomes. The exposures were (1) receipt of empiric antibiotics in <=1 hour and (2) receipt of appropriate antibiotics in <=1 hour. The primary outcome was development of new or progressive multiple system organ dysfunction syndrome (NP-MODS). The secondary outcome was mortality. Results: Among 321 patients admitted to intensive care, 48% (n = 153) received empiric antibiotics in <=1 hour. These patients were more ill at presentation with significantly greater median pediatric index of mortality 2 (PIM2) scores and were more likely to receive recommended resuscitation in the ED (61% vs 14%); however, rates of NP-MODS (9% vs 12%) and hospital mortality (7% vs 4%) were similar to those treated later. Early, appropriate antibiotics were administered to 33% (n = 67) of patients with identified or suspected bacterial infection. These patients had significantly greater PIM2 scores but similar rates of NP-MODS (15% vs 15%) and hospital mortality (10% vs 6%) to those treated later. Conclusions: Critically ill children with septic shock treated in a children's hospital ED who received antibiotics in <=1 hour were significantly more severely ill than those treated later, but they did not have increased risk of NP-MODS or death. PMID- 26837957 TI - Enhancing the hermeneutic single-case efficacy design: Bridging the research practice gap. AB - Systematic case study designs are emerging as alternative paradigm strategies for psychotherapy and social science research. Through enhanced sensitivity to context, these designs examine idiographic profiles of causal processes. We specifically advocate the use of the hermeneutic single-case efficacy design (HSCED). HSCED has recently been used to investigate the efficacy of an existing therapy with a new population (Observed and Experiential Integration for athlete performance barriers) and an emerging therapy (Lifespan Integration Therapy). We describe innovations in HSCED that were implemented for these studies. These developments include (a) integrating psychotherapists as case developers, (b) incorporating multiple cases in one investigation, and (c) tailoring the repertoire of assessment tools. These extensions strategically incorporated principles of contextual paradigms in HSCED, thus complementing single-case designs that neglect idiographic contexts. We discuss recommendations for using HSCED in practice-based research, highlighting its potential as a bridge to address the research-practice gap. PMID- 26837959 TI - Nasopharynx carcinoma: A rare primary for bilateral breast metastasis. PMID- 26837958 TI - Unique roles of nanotechnology in medicine and cancer-II. AB - Applications of nanotechnology in medicine and cancer are becoming increasingly popular. Common nanomaterials and devices applicable in cancer medicine are classifiable as liposomes, polymeric-micelles, dendrimers, nano-cantilevers, carbon nanotubes, quantum dots, magnetic-nanoparticles, gold nanoparticles (AuNPs) and certain miscellaneous nanoparticles. Here, we present review of the structure, function and utilities of the various approved, under trial and pretrial nanodevices applicable in the cancer care and medicine. The liposomes are phospholipid-vesicles made use in carrying drugs to the target site minimizing the bio-distribution toxicity and a number of such theranostics have been approved for clinical practice. Newly worked out liposomes and polymeric micelles are under the trail phases for nano-therapeutic utility. A multifunctional dendrimer conjugate with imaging, targeting and drug molecules of paclitaxel has been recently synthesized for cancer theranostic applications. Nano-cantilever based assays are likely going to replace the conventions methods of chemical pathological investigations. Carbon nanotubes are emerging for utility in regenerative and cancer medicine. Quantum dots hold great promise for the micro-metastasis and intra-operative tumor imaging. Important applications of magnetic nanoparticles are in the cardiac stents, photodynamic therapy and liver metastasis imaging. The AuNPs have been employed for cell imaging, computed tomography and cancer therapy. Besides these categories, miscellaneous other nanoparticles are being discovered for utility in the cancer diagnosis and disease management. However, the use of nanoparticles should be cautious since the toxic effects of nanoparticles are not well-known. The use of nanoparticles in the clinical practice and their toxicity profile require further extensive research. PMID- 26837960 TI - Applicability of RNA interference in cancer therapy: Current status. AB - Cancer is a manifestation of dysregulated gene function arising from a complex interplay of oncogenes and tumor suppressor genes present in our body. Cancer has been constantly chased using various therapies but all in vain as most of them are highly effective only in the early stages of cancer. Recently, RNA interference (RNAi) therapy, a comparatively new entrant is evolving as a promising player in the battle against cancer due to its post-transcriptional gene silencing ability. The most alluring feature of this non-invasive technology lies in its utility in the cancer detection and the cancer treatment at any stage. Once this technology is fully exploited it can bring a whole new era of therapeutics capable of curing cancer at any stage mainly due to its ability to target the vital processes required for cell proliferation such as response to growth factors, nutrient uptake/synthesis, and energy generation. This therapy can also be used to treat stage IV cancer, the most difficult to treat till date, by virtue of its metastasis inhibiting capability. Recent research has also proved that cancer can even be prevented by proper modulation of physiological RNAi pathways and researchers have found that many nutrients, which are a part of routine diet, can effectively modulate these pathways and prevent cancer. Even after having all these advantages the potential of RNAi therapy could not be fully tapped earlier, due to many limitations associated with the administration of RNAi based therapeutics. However, recent advancements in this direction, such as the development of small interfering RNA (siRNA) tolerant to nucleases and the development of non-viral vectors such as cationic liposomes and nanoparticles, can overcome this obstacle and facilitate the clinical use of RNAi based therapeutics in the treatment of cancer. The present review focuses on the current status of RNAi therapeutics and explores their potential as future diagnostics and therapeutics against cancer. PMID- 26837961 TI - Superior vena cava syndrome: Initial presentation of acute myeloid leukemia in a child. PMID- 26837962 TI - miR-17-92 host gene, uderexpressed in gastric cancer and its expression was negatively correlated with the metastasis. AB - BACKGROUND: This study aimed to evaluate the expression of miR-17-92 host gene (MIR17HG), in gastric cancer and paired normal adjacent tissues for the 1st time. METHODS: Using quantitative real-time-polymerase chain reaction, the MIR17HG expression was assessed in 30 paired tumoral and nontumoral gastric tissue samples. RESULTS: Our results showed that this transcript was significantly underexpressed in gastric tumors compared with normal ones. Furthermore, there was an association between the expression levels of MIR17HG and gastric cancer grades and stages. Moreover, the expression level of MIR17HG was conversely associated with the size of tumoral specimens in early stages (stages I and II). We also observed an association between the presence of metastasis and lower expression of MIR17HG. CONCLUSION: Our results suggest that MIR17HG gene expression is dysregulated in gastric cancer in which it may indicate a tumor suppressive function of this miRNA cluster host gene in gastric cancer. PMID- 26837963 TI - Feasibility and efficacy of salvage radiotherapy with concurrent weekly topotecan in recurrent primitive neuroectodermal tumor. PMID- 26837951 TI - Animal models of osteoarthritis: classification, update, and measurement of outcomes. AB - Osteoarthritis (OA) is one of the most commonly occurring forms of arthritis in the world today. It is a debilitating chronic illness causing pain and immense discomfort to the affected individual. Significant research is currently ongoing to understand its pathophysiology and develop successful treatment regimens based on this knowledge. Animal models have played a key role in achieving this goal. Animal models currently used to study osteoarthritis can be classified based on the etiology under investigation, primary osteoarthritis, and post-traumatic osteoarthritis, to better clarify the relationship between these models and the pathogenesis of the disease. Non-invasive animal models have shown significant promise in understanding early osteoarthritic changes. Imaging modalities play a pivotal role in understanding the pathogenesis of OA and the correlation with pain. These imaging studies would also allow in vivo surveillance of the disease as a function of time in the animal model. This review summarizes the current understanding of the disease pathogenesis, invasive and non-invasive animal models, imaging modalities, and pain assessment techniques in the animals. PMID- 26837964 TI - Evaluating of suppressor of zeste 12 and chromobox homolog 8 genes expression showed two possible origins for gastric cancer development. AB - CONTEXT: Changes in genome, made by multiple genetic and epigenetic alterations result to the cancer initiation and progression. Suppressor of zeste 12 (SUZ12) and chromobox homolog 8 (CBX8) proteins are two components of epigenetic regulators that their function in the initiation and progression of cancers are not well-understood. AIMS: The role of SUZ12 and its target CBX8 is examined. SETTINGS AND DESIGN: Comparing the expression levels of SUZ12 and CBX8 between 30 gastric tumor and their marginal tissues. MATERIALS AND METHODS: Quantitative reverse transcription polymerase chain reaction technique was performed. STATISTICAL ANALYSIS: Statistical comparison was carried out using Statistical Program for Social Sciences software 16.0 (Released 2007, SPSS for Windows. SPSS Inc., Chicago, IL, USA) and (GraphPad Prism version 5 for Windows, GraphPad Software, La Jolla, California USA, ww.graphpad.com). RESULTS: Despite the obvious differences in the expression of these genes in each sample for tumor and its marginal tissue, statistical analysis did not show significant differences in the mean of expression for SUZ12 and CBX8 genes in total. Due to the variation in expression levels, the samples could be divided into two groups for each gene; group 1, in which the genes were overexpressed in tumor and group 2, in which the genes were down regulated in tumor samples. CONCLUSION: We found that in each group, the difference in the SUZ12 and CBX8 genes expression were significantly divergent between tumors and their marginal tissues. It means that the regulatory mechanisms involved in developing and controlling the process of gastric cancer pathogenesis is more complex than it thought. These results also bring new evidence on the possible double origin for gastric cancer development, bone marrow-derived cells and tissue stem cells. PMID- 26837965 TI - Visfatin effects on telomerase gene expression in AGS gastric cancer cell line. AB - AIM: The aim of this study was to assess visfatin expression and its effect on human telomerase gene expression in AGS gastric cancer cell line. MATERIALS AND METHODS: In this study, human gastric cancer (AGS) cell line was established as an in vitro model. Reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay was performed to show that visfatin expression in messenger ribonucleic acid (mRNA) and protein level respectively. After stimulating with increasing concentrations of visfatin for times of 24 h and 48 h, cell proliferation was assessed by 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl) 2H-Tetrazolium-5-Carboxanilide (XTT) assay. In order to investigate telomerase gene expression affected by visfatin in AGS cell line, total RNA was extracted and complementary deoxyribonucleic acid was synthesized buy using commercially available kits. Expression of human telomerase reverse transcriptase (hTERT) mRNA was carried out by real-time RT-PCR. RESULTS: After visfatin treatment gastric cell line proliferation was enhanced and was increased the expression of hTERT. CONCLUSIONS: The obtained data showed that visfatin induces endogenously gastric cancer cell proliferation and increases telomerase (hTERT) gene expression, as a cancer gene. Based on this study, it is suggested that expression of this adipocytokine protein in real samples could be biomarker for gastric cancer. PMID- 26837966 TI - Bursectomy for gastric cancer: What does the evidence indicate? AB - Radical resection of the bursa omentalis (radical bursectomy) as part of a curative resection for gastric cancer has been advised for close to a century. However, the postulated associated morbidity and lack of a clear benefit in terms of survival preclude its routine use. To objectively review the available evidence on the role of bursectomy as part of a curative resection for gastric cancer. A systematic search of the scientific literature was carried out using Embase, PubMed, MedLine and the Cochrane central register of controlled trials for the years 1965-2013 to obtain access to all publications, especially randomized controlled trials (RCTs), systematic reviews and meta-analyses involving bursectomy in gastric cancer with the appropriate specific search terms, namely, "bursectomy," "stomach cancer," "gastric cancer," "survival," "morbidity," "outcomes" and "RCTs". Using the above search strategy, a total of 29 publications was retrieved of which five publications were identified describing bursectomy and its outcomes in gastric cancer. These included three retrospective cohort studies and two publications from a single RCT. Bursectomy do not appear to add the morbidity or mortality of the overall surgery. However, it did not appear to significantly improve overall survival neither in the retrospective cohort studies nor in the only RCT. The evidence to date is insufficient to suggest any additional benefit of routine bursectomy to a radical gastrectomy with D2 lymphadenectomy for gastric cancer. Results of an on-going RCT are awaited to determine if bursectomy may further improve overall survival in patients with advanced T-stage of disease. PMID- 26837967 TI - Leukemic transformation in Fanconi's anemia. PMID- 26837968 TI - Results of combination chemotherapy and radiation therapy in non-metastatic gastric cancer in Yazd--Iran. AB - BACKGROUND: Gastric cancer is the first cause of cancer death in Iran. Most of the patients are diagnosed in advanced stages and survival rate is low. The aim of this study was to evaluate the survival rate of patients with gastric and gastroesophageal junction adenocarcinoma receiving combination chemotherapy and radiation therapy in Iran. MATERIALS AND METHODS: This study was conducted on 53 patients with gastric or gastroesophageal junction adenocarcinoma referring to Shahid Ramezanzadeh Radiation Oncology Center between 2004 and 2010. All patients underwent surgical operation, chemotherapy, and radiotherapy. Data contained in patients' records were extracted and follow-up was conducted through telephone contacts. To analyze the data, Kaplan Meier curves, and SPSS software were employed. RESULTS: Seventeen (32.1%) patients were female and 36 (67.9%) were male. Mean age was 58.32 years. In 14 patients (26.9%) no lymph node was resected or reported by the pathologist. In 29 patients (54.7%) one to six lymph nodes were found, and in10 patients (18.9%) seven lymph nodes or more were detected. In two patients, (3.77%) more than 15 lymph nodes were resected. Surgical staging was impossible for 16 patients (30.2%). Mean survival was 50.9 months and median survival was 51 months. 3,5 and 7 year survival rates were 73%, 36%, and 18% respectively. None of the variables had a significant relation to survival. CONCLUSIONS: Despite inadequate surgery, the survival rate in our study is one of the best one reported in our country. We think this advantage may be due to poly drug chemotherapy and sequential radiation therapy. PMID- 26837969 TI - Fungating extramedullary plasmocytoma of breast; a unique case presentation. PMID- 26837970 TI - Is histologic differentiation a prognostic indicator for gastric carcinoma patients with curative resection? AB - BACKGROUND: The prognostic relevance of histologic differentiation in gastric carcinoma patients with curative resection is unclear. We analyzed the clinicopathologic features of gastric carcinoma patients with curative resection according to the histologic differentiation and evaluated surgical outcome. MATERIALS AND METHODS: Of 1198 gastric carcinoma patients with curative resection (American joint committee on cancer, Stages I-III), 274 (22.9%) had well differentiated, 331 (27.6%) had moderately differentiated and 593 (49.5%) had poorly differentiated gastric carcinomas. RESULTS: Patients with the poorly differentiated type had more prominent serosal invasion, much more lymph node involvement and more advanced stage than patients with the well-differentiated type. The overall survival rate was higher for patients with a well differentiated gastric carcinoma than for patients with a poorly differentiated type. Using Cox's proportional hazard regression model, histologic differentiation was found to be a statistically significant prognostic parameter (risk ratio, 1.41; 95% confidence interval, 1.028-1.922; P < 0.05). CONCLUSION: Our results suggest that patients with a well-differentiated gastric carcinoma have a good prognosis compared with those with a poorly differentiated type. Therefore, histologic differentiation can be used as a prognostic indicator in gastric carcinoma patients with curative resection. PMID- 26837971 TI - Evaluating the relation between patients-related factors and dissected lymph node ratio in gastric cancer. AB - BACKGROUND: Gastric cancer is a forth common malignancy world-wide and the second most common cause of cancer-related deaths. According to the current International Union Against Cancer staging system, nodal status is categorized based on the number of metastatic lymph nodes (LNs). Some groups have recently proposed the metastatic lymph node ratio (MLR) (the ratio between metastatic LNs and total dissected LNs; MLR) as an alternative prognostic factor. The aim of the present study is to evaluate the relationship between MLR and different clinico pathologic factors including patients' age, tumor grade, stage, sites of involvement and disease prognosis. METHODS: Atotal of 70 patients with gastric adenocarcinoma who underwent gastrectomy with negative margin and LN resection during 2004-2009 and were referred to Radiotherapy-Oncology Department of Name of Hospital, Name of City, were included in the study. MLR status was divided to five groups. Collected data were analyzed with SPSS 16 (SPSS Inc., Chicago, IL, USA). RESULTS: The difference between MLR groups in age was significant; older patients had lower MLR (P = 0.01). The ratio of male to female was 5.3, which indicated higher prevalence of gastric cancer in males. The difference between MLR groups for tumor location, tumor stage, disease free periods and tumor T stages were not significant. A significant relation existed between different stages of LN involvement and MLR; and also between cancer stages and MLR. CONCLUSION: We found a significant relation between MLR and cancer stage and metastatic LN. Due to small sample size and short period of follow-up, we could not find significant relation between MLR and other factors such as depth of tumor invasion, disease free period and tumor grading. In conclusion with regards to our results and other similar studies' results, we acknowledge the importance of MLR in determining patients' prognosis in gastric cancer. PMID- 26837972 TI - Inguinal lymphnode metastatic testicular seminoma: A case report and review of literature. PMID- 26837973 TI - Synchronous primary cancers in the head and neck region and upper aero digestive tract: Role of triple endoscopy. AB - BACKGROUND: Patients with cancers in the head and region are at increased risk of developing synchronous primary cancers. AIM: The aim of this study is to see the role of endoscopy in the pre-therapeutic works-up of patients with the cancers in the head and neck region. MATERIALS AND METHODS: Data of head and neck cancer patients from January 2010 to December 2011 were obtained from the hospital cancer registry for retrospective analysis of patients with synchronous cancers. All synchronous malignancies were analyzed for distribution of sites, association with smoking history and the average age of patients at presentation with synchronous cancers. The Chi-square test for association of upper aero digestive tract (UADT) and smoking and statistical formula of mode for average age have been employed for analyzing results. RESULTS: Incidence of synchronous primaries has been found to be 1.43% and mostly males were affected. The common index sites for synchronous primaries are oropharynx 22 (36.6%), oral cavity 14 (23.3%), hypopharyx 12 (20%) and larynx eight (13.3%) cases in decreasing order, 58.3% synchronous occurred at esophagus and 0.83% of all head and neck cancers developed synchronous primary at esophagus. Association of UADT synchronous cancers with smoking (odds ratio = 13.42, Chi-square 7.12 at 95% confidence interval, P = 0.0076) is highly significant and the average age is 62.6 years in males and 62 years in females. CONCLUSION: Endoscopy can be rationally used during the pre-therapeutic work-up of patients with a history of smoking and/or in patients over the age of 62 years. Instead of complete upper gastro intestinal endoscopy up to the second part of duodenum, only esophagoscopy is needed for the detection of synchronous primary of upper aero-digestive tract in cancers of the head and neck region. PMID- 26837974 TI - Clinicopathological characteristics of ameloblastomas in Western Uttar Pradesh population: An institutional study. AB - OBJECTIVE: The aim of this study was to compare the clinical, radiologic, and histopathological features of 28 intraosseous ameloblastomas. In addition, we compared the data obtained in this study with that of previous studies. MATERIALS AND METHODS: Data with regard to age, gender, clinical manifestation, radiographic aspect, anatomical distribution, and histopathological subtypes were analyzed in 28 subjects. RESULTS: The patients' age ranged from 7 years to 65 years (mean, 30.4 years). Sixteen (57.14%) of the 28 subjects were males, and 12 (42.85%) were females. A total of 22 cases (78.5%) were located in the mandible, posterior region was more often affected with 17 cases (77.27%) than only 5 cases (22.72%) in the anterior segment. Swelling was the most common symptom and was experienced by 12 (42.85%) patients. Radiographically, 14 cases (50%) were multilocular with a well-demarcated border. Of the remaining 14 cases, 10 were unilocular and 4 were unknown in appearance. The most common histopathological pattern was follicular followed by plexiform or acanthomatous. CONCLUSIONS: The clinical epidemiological profile to patients in the present study is similar to that in other populations, with follicular ameloblastoma being the most common histological subtypes seen. PMID- 26837975 TI - Giant testicular tumor with pulmonary metastases: Stroke as the initial manifestation. PMID- 26837976 TI - No evidence of association of xenotropic murine leukemia virus-related virus with oral cancers: Experience from a tertiary care center in South India. AB - BACKGROUND: Development of oral cancer, a widely prevalent cancer in India, is multifactorial with increased risk in those habituated to smoking, consuming alcohol and chewing paan and tobacco. This does not preclude other etiological factors in the causation of this cancer. Exploratory studies on several oncogenic viruses have found varied associations with oral cancers. AIM: The aim of this study was to explore the association of xenotropic murine leukemia virus-related virus, (XMRV) a retrovirus recently implicated in oncogenesis in humans, with oral cancers. SETTINGS AND DESIGN: The presence of XMRV proviral deoxyribonucleic acid (DNA) was evaluated by standard nucleic acid amplification from DNA extracted from representative bits of tumor tissues and adjacent normal tissues from surgically resected specimens sent post-operatively for routine histopathological testing. MATERIALS AND METHODS: This prospective study comprised 109 patients with a provisional diagnosis of oral cancer who were operated at the Oral Oncology Department of Kidwai Memorial Institute of Oncology, over a period of 10 months. RESULTS: XMRV was not found in any of the tumor tissues (squamous cell carcinomas - 98; verrucous carcinomas - 4) nor in any of the normal tissues. It is thus important that the absence of this oncogenic virus in all the cases makes the association of XMRV with oral cancers very unlikely. CONCLUSIONS: There is a need to investigate potentially oncogenic viruses in other solid tumors and in larger sample sizes. Any such association could have implications in detecting, preventing and treating these cancers. PMID- 26837977 TI - A prospective study to assess the efficacy and toxicity of 5-flurouracil and cisplatin versus taxane and cisplatin as induction chemotherapy in locally advanced head and neck squamous cell cancer in a regional cancer center in India. AB - AIM: The aim of this study is to assess the efficacy and toxicity of 5 flurouracil (5-FU) and cisplatin (PF) versus taxane and cisplatin (TP) as induction chemotherapy in locally advanced head and neck squamous cell cancer. MATERIALS AND METHODS: There were 50 patients in each arm, matched for age, performance state, site and stage of disease. PF arm (cisplatin - 100 mg/m2 D1, 5 FU - 1000 mg/m2 D1-D5) TP arm (docetaxel - 75 mg/m2 or paclitaxel - 175 mg/m2 on D1, cisplatin 75 mg/m2 on D2), received once in 3 weeks for 3 cycles. Patients without progressive disease underwent either surgery or chemoradiation. The primary end point was overall response rate (ORR) and secondary endpoint was toxicity. RESULTS: In a total of 100 patients in our study, 44 in PF and 47 in TP arm were evaluable. ORR was 86.6% in PF arm and 82.9% in TP arm (P = 0.71).There were more Grade 3 or 4 events of neutropenia, mucositis (P <= 0.05) and myelosuppression diarrhea, febrile neutropenia (P >= 0.05) in PF arm compared with TP arm. Post-chemotherapy hospital admissions due to toxicity were more frequent in PF arm (38.6% vs. 19%), dropout rate due to toxicity (9% vs. 0%) and deaths (6.8% vs. 2.1%) were more common in PF arm compared with TP arm. CONCLUSION: TP induction chemotherapy better tolerated than PF, which has similar efficacy, further multicenter randomized controlled studies; involving a large sample size is needed to confirm our data. PMID- 26837978 TI - Indirect evidences of functionality of insulinoma on FDG-PET: The 'whole body metabolism' advantage and its clinical implications. PMID- 26837979 TI - Is taxane/platinum/5 fluorouracil superior to taxane/platinum alone and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers? AB - BACKGROUND: Cisplatin and 5 fluorouracil drug combination is inferior to the combination of taxane with these 2 drugs. However, often in clinical practice at our center giving TPF (docetaxel, cisplatin, 5 fluorouracil) is difficult in view of logistics and tolerance issues. In such a scenario, we prefer to use the 2 drugs combination of platinum and taxane. However, no study has addressed whether a 2 drugs combination, which includes taxane is inferior to the 3 drugs combination and which the taxane of choice is in the 2 drugs combination of taxane and platinum. METHODS: This is a retrospective analysis of prospectively collected data of patients undergoing induction chemotherapy (IC) in oral cavity cancers from 2010 to 2012. We chose for analysis those patients who had a baseline scan done within 4 weeks of starting therapy and a follow-up scan done within 2 weeks of completion of the second cycle of IC. Response was scored in accordance with RECIST version 1.1. Chi-square analysis was done to compare response rates (RRs) between regimens. RESULTS: Two hundred and forty-five patients were identified. The median age was 45 years (24-70 years), 208 (84.9%) were male patients, and 154 patients (62.9%) had primary in the Buccal mucosa. The regimens received were TPF 22 (9%), docetaxel + cisplatin 97 (39.6%), paclitaxel + cisplatin 89 (36.3%), docetaxel + carboplatin 16 (6.5%) and paclitaxel + carboplatin 21 (8.6%). The overall RRs were complete response, partial response, stable disease and progressive disease in 4 (1.6%), 56 (22.9%), 145 (59.2%) and 40 (16.3%). The 3 drugs regimen (TPF) had 50% RR as compared to 22% RR with 2 drugs regimen (P = 0.004). Docetaxel containing regimens had 30.3% RR as compared to 17.2% RR with paclitaxel containing regimens (P = 0.094). CONCLUSIONS: TPF has better RR than a 2 drugs taxane-containing regimen and docetaxel leads to a better RR than paclitaxel for IC in locally advanced oral cavity cancers. PMID- 26837980 TI - Response to taxane-based chemotherapy in metastatic eccrine porocarcinoma with extensive cutaneous involvement. PMID- 26837981 TI - Efficacy of argyrophilic nucleolar organizing region analysis using computer assisted and manual in oral leukoplakia: A comparative study. AB - OBJECTIVE: Nucleolar organizer regions are loops of DNA containing ribosomal RNA genes and presumably are associated with ribosomal RNA activity, protein synthesis, and cell proliferation. Argyrophilic nucleolar organizer region (AgNOR) count has been suggested as an objective method in differentiating dysplastic lesions from non-dysplastic lesions. MATERIALS AND METHODS: This descriptive study was done on archival paraffin blocks (n = 60), consisting of 10 normal human oral epithelium, 22 cases of non-dysplastic leukoplakia (NDLK), and 28 cases of dysplastic leukoplakia (DLK). The AgNORs were counted with the aid of a manual using conventional light microscopy and photographs of the same were taken and analyzed using Image Pro Express 6.0 (Media Cybernetic Inc., USA) for windows. RESULTS: The mean AgNOR count per nucleus was found to be higher in patients with DLK as compared to NDLK and controls using both manual counting and image analysis method and on comparing both the techniques, image analysis provide a more accurate reflection of AgNOR counts than manual counting. CONCLUSION: To conclude, reliability of computerized image technique of AgNOR count is the most appropriate marker to differentiate between dysplastic and NDLK. Computer-assisted image analysis system was found to be an effective tool in achieving high reproducibility as compare to manual. PMID- 26837982 TI - Hyperpigmented mycosis fungoides with ecthyma gangrenosum. PMID- 26837983 TI - Phenytoin mouthwash to treat cancer therapy-induced oral mucositis: A pilot studyPrimary neuroendocrine carcinoma of breast: A rare tumor. AB - BACKGROUND: Oral mucositis is one of the most common side effects of cancer therapy with no definite treatment. Phenytoin has positive effects on healing of mucosal and dermal wounds. In this study efficacy of 1% phenytoin mouthwash on severity of mucositis (on the basis of WHO scale), pain relief (based on Visual Analogue Scale), and improvement of patients' quality of life (on the basis of EORTC-QLQ-H and N35 questionnaire) was evaluated. MATERIALS AND METHODS: In a pilot -double-blind randomized clinical trial, eight patients in study group were given 1% phenytoin mouthwash while eight patients in control group used normal saline. Data analysis was performed by Mann-Whitney and Repeated Measured ANOVA tests. RESULTS: Reduction of mucositis severity was observed, but the difference was not significant. On the other hand, patients on phenytoin therapy had better pain relief (VAS# 6.75 +/- 1.58 at the beginning of the study reached to # 3.75 +/- 1.16 after 3 weeks in phenytoin group) and improvement in quality of life (score of QOL was 70.63 +/- 5.5 that reached to 63.61 +/- 6.39 in phenytoin group) than normal saline group significantly (P < 0.05). CONCLUSION: One percent phenytoin mouthwash caused pain relief and improvement of life quality significantly in patients with mucositis due to cancer therapy, but it did not reduce the severity of mucositis in a statistically significant scale. PMID- 26837984 TI - Primary neuroendocrine carcinoma of breast: A rare tumor. PMID- 26837985 TI - Stromal myofibroblasts in oral squamous cell carcinoma and potentially malignant disorders. AB - INTRODUCTION: Concurrent with the progression of a non- diseased epithelium to the pre-cancerous epithelium to carcinoma, the stroma also undergoes modifications. Myofibroblasts are important stromal cells that play a crucial role in carcinogenesis. The current study investigated the presence of myofibroblasts in healthy oral mucosa, potentially malignant disorders (PMDs) and squamous cell carcinoma (SCC). MATERIALS AND METHODS: The study material consisted of a total of 106 samples categorized into three groups, namely, Group I - Oral SCC (OSCC) (n = 42), Group II - PMDs (n = 32) and Group III - Oral healthy mucosa (n = 32) subjected to immunohistochemical analysis using alpha Smooth Muscle Actin. RESULTS: Among the 42 cases of OSCC, the staining index was negative in 23 cases (54.7%), low in 9 cases(21.4%) and moderate in 10 cases (23.8%). The stroma of cases of verrucous carcinoma, cases of Hyperkeratosis with epithelial dysplasia, 77.5% of the cases of oral Submucous Fibrosis (OSMF) and healthy oral mucosa were devoid of myofibroblasts resulting in a grade of "0" in all cases.Two of the cases of OSMF (12.5%) showed low staining index for myofibroblast. There was a significant difference in the myofibroblasts expression between the Groups (Kruskal-Wallis test P<0.001). CONCLUSION: The findings of the current study justify "myofibroblast" as one among the key stromal element in tumor progression. Future studies involving a larger sample size along with follow up of patients with PMDs are essential to identify the exact stage in which they emerge in the stroma of these lesions. PMID- 26837986 TI - Tackling the delay: A unified approach. PMID- 26837987 TI - Developing a comprehensive cancer specific geriatric assessment tool. AB - BACKGROUND: Population aging is one of the most distinctive demographic events of this century. United Nations projections suggest that the number of older persons is expected to increase by more than double from 841 million in 2013 to >2 billion by 2050. It is estimated that 60% of the elderly patients may be affected by cancer and may present in the advanced stage. The aim of this paper was to develop a brief cancer-specific comprehensive geriatric assessment tool for use in a geriatric population with advanced cancer that would identify the various medical, psychosocial, and functional issues in the older person. METHODS: Literature on assessment of geriatric needs in an oncology setting was reviewed such that validated tools on specific domains were identified and utilized. The domains addressed were socioeconomic, physical symptoms, comorbidity, functional status, psychological status, social support, cognition, nutritional status and spiritual issues. Validated tools identified were Kuppuswamy scale (socioeconomic), Edmonton Symptom Assessment Scale (Physical symptoms) and SAKK cancer-specific geriatric assessment tool, which included six standard geriatric measures covering five geriatric domains (comorbidity, functional status, psychological status, social support, cognition, nutritional status). The individual measures were brief, reliable, and valid and could be administered by the interviewer. CONCLUSION: The tool was developed for use under the geriatric palliative care project of the department of palliative medicine at Tata Memorial Hospital, Mumbai. We plan to test the feasibility of the tool in our palliative care set-up, conduct a needs assessment study and based on the needs assessment outcome institute a comprehensive geriatric palliative care project and reassess outcomes. PMID- 26837988 TI - Proximal type of epithelioid sarcoma of back with metastasis to humerus at presentation: Indicating aggressive behavior. PMID- 26837989 TI - Palliative care in India: Situation assessment and future scope. AB - Palliative care is an approach that improves the quality of life of patients and their families facing the problems associated with life-threatening illness, through prevention and relief of suffering by means of early identification, assessment and treatment of pain, and other problems - physical, psychosocial, and spiritual. It is estimated that in India the total number of people who need palliative care is likely to be 5.4 million people a year. Though palliative care services have been in existence for many years, India ranks at the bottom of the Quality of Death index in overall score. However there has been steady progress in the past few years through community-owned palliative care services. One of the key objectives of the National Programme for prevention and control of cancer, diabetes, cardiovascular diseases, and stroke is to establish and develop capacity for palliative and rehabilitative care. Community models for the provision of home-based palliative care is possible by involving community caregivers and volunteers supervised by nurses trained in palliative care. Training of medical officers and health care professionals, and sensitization of the public through awareness campaigns are vital to improve the scope and coverage of palliative care. Process of translating palliative care plan into action requires strong leadership, competent management, political support and integration across all levels of care. PMID- 26837990 TI - Delay in presentation to the hospital and factors affecting it in breast cancer patients attending tertiary care center in Central India. AB - INTRODUCTION: Despite lower incidence of breast cancer in India, the total number of cases and the net mortality is high. To reduce this increasing load of mortality due to breast cancer we need to lay emphasis on early detection and increased use of systemic therapy. Early detection itself depends on early presentation to a health facility; thus, it is important to identify factors affecting delay in a presentation to hospital. AIM AND OBJECTIVES: To study the clinico-social profile of breast carcinoma patients attending a tertiary care hospital and to study the time lag since detection of lump by women and presentation to the hospital and factors affecting them. MATERIALS AND METHODS: A total of 120 primary breast cancer patients visiting a tertiary care hospital over a period of 7 months (August 2010 to February 2011) were taken up for study. A detailed retrospective analysis of patients was done according to planned proforma. OBSERVATIONS: Maximum study subjects were in the age group of 41-50 years. Right and left breasts were equally affected. The most common histo pathological type of breast carcinoma observed was invasive ductal carcinoma (NOS) in 105 (87.50%) cases. Majority of the cases were in stage III or stage II. The median time lag self-detection of lump in the breast by women and presentation to the hospital was 6 months. Women living in a rural area, those with lower socio-economic status and those with older age tend to assess health care late. CONCLUSIONS: Carcinoma of the breast is a common cancer affecting young to middle age group with invasive ductal carcinoma being the most common histological type. Delay in presentation and late stage presentation is a major concern. Hence, proper awareness and screening programmers are needed to identify, inform and educate these categories of women. PMID- 26837991 TI - F-18 FDG PET/CT in restaging of a rare case of malignant cystosarcoma phylloides. PMID- 26837992 TI - Trace elements; copper, zinc and selenium, in breast cancer afflicted female patients in LAUTECH Osogbo, Nigeria. AB - BACKGROUND: There is an indication of the possibility of the direct or indirect influence of trace element in the development and prevention of malignant diseases, the contribution of the trace elements in the etiology of breast cancer has been under scrutiny. AIMS: The aim of this study was to determine the serum concentration of trace element in serum of female patients with breast cancer in comparison with healthy controls. SETTINGS: Breast Clinic of the Department of Surgery LAUTECH University teaching hospital Osogbo, in south-western Nigeria. MATERIALS AND METHODS: A cross-sectional age matched controlled prospective study wherein the venous blood sample of 30 patients with breast cancer and 30 healthy volunteers as controls were analyzed using atomic absorption spectrophotometry. The collected data were analyzed using statistical package for the social sciences (SPSS Inc) 16. RESULT: The mean serum concentration of the copper, zinc and selenium were 95.3 +/- 4.9 ug/dl and 65.2 +/- 15 ug/dl, 62.7 +/- 15.7 ug/dl and 93.5 +/- 7.2 ug/dl, 45.0 +/- 4.6 ug/l and 76.4 +/- 8.9 ug/l in the two groups respectively. The concentrations of copper and copper-zinc ratio (C/Z) were significantly higher in the cancer bearing group compared to the controls (C/Z 1.6 +/- 0.5 against 0.70 +/- 0.14 the P < 0.01). The concentration of zinc and selenium in the venous blood of the breast cancer patients showed inverse relationship while that of the control showed a direct relationship (-0.03 against 0.09). In the breast cancer patients the correlation of copper and zinc, copper and selenium and zinc and selenium showed inverse relationships, none of the relationships was statistically significant. CONCLUSION: We found a significant association between the serum concentration of trace elements and breast cancer. PMID- 26837993 TI - Duodenal adenocarcinoma: A rare cause of chyloperitoneum (chylous ascites). PMID- 26837994 TI - Correlation of various histopathologic prognostic factors with Nottingham prognostic index and microvessel density in invasive breast carcinoma: A study of 100 cases. AB - BACKGROUND: Nottingham prognostic index (NPI) is a widely used integrated prognostic variable in patients with breast cancer. NPI has been correlated with tumor size, grade, lymph node stage and patient survival. The present study aimed at evaluating and correlating the various clinical and pathologic features of breast carcinoma with NPI. METHODS: This study included 100 consecutive cases of primary breast carcinoma over a period of 2 years. Demographic data was noted and histomorphological features like tumor size, grade, lymph node involvement, necrosis, vascular invasion etc., were assessed. NPI was calculated as reported in the literature. Immunohistochemical staining for hormone receptors and CD34 (to calculate microvessel density [MVD]) was performed. Statistical analysis was used for correlation. RESULTS: Of the 100 cases, 54% of the tumors were in T2 tumor size category (2-5 cm) and lymph node metastasis in 48% of the cases. NPI ranged from 2.3 to 7.3 with 54% of the cases in the intermediate NPI group (3.41 5.4). The mean MVD was 160.93 (+/-69.4/mm2). On statistical analysis, tumor size and grade, lymph node stage, mitotic rate, nuclear pleomorphism, necrosis and MVD showed a correlation with NPI (P < 0.05). CONCLUSION: NPI is an important and useful prognostic indicator for breast cancer patients, which shows the correlation with other histomorphological prognostic features as well. PMID- 26837995 TI - Renal impairment in prostate cancer: A close look is important. PMID- 26837996 TI - Impact of post-operative radiation on coronary arteries in patients of early breast cancer: A pilot dosimetric study from a tertiary cancer care center from India. AB - BACKGROUND: The significant impact of postoperative radiotherapy (PORT) on cardiac morbidity in patients of early breast cancer (EBC) undergoing breast conserving surgery has been shown in different studies. The present study was conducted to assess the impact of surgery and the side of involvement on radiation dose to left anterior descending artery (LAD) and Left circumflex coronary artery (LCx). MATERIALS AND METHODS: Totally, 58 patients of EBC were randomly chosen for this dosimetric study and planned with tangential field technique without intensity modulation (IM). Heart, LAD, and LCx (n = 55) were contoured. Dose volume histograms were analyzed to determine the Dmax (maximum dose) and Dmean (mean dose) of LAD and LCx. Student's t-test was used for comparative analysis of the means. RESULTS: The mean Dmax of LAD for left (L) EBC was 3.17 Gray (Gy) while for right (R) EBC it was 0.86 Gy (P = 0.007; 95% C.I, 1.14-3.48). The mean Dmean of LAD for L-EBC and R-EBC were 1.97 Gy and 0.79 Gy, respectively (P = 0.029; 95% C.I, 0.77-1.60). The mean-Dmax of LCx for patients with L-EBC (2.9 Gy; range: 1.2-4.35 Gy) was statistically higher than that for R EBC (1.3 Gy; range: 0.7-3.2 Gy) (P = 0.045). The mean-Dmean of LCx for L-EBC (2.1 Gy; range: 0.6-3.6 Gy) was also significantly higher than that of L-EBC (0.9 Gy; range: 0.7-2.1 Gy) (P = 0.03). There was no significant impact of the pattern of surgery on LAD dose, but significance was noted for LCx dose parameters (P = 0.04 and 0.08 for m-Dmax and m-Dmean of LCx). CONCLUSION: This pilot dosimetric study confirms the assumption that patients with left-sided EBC are at higher risk of developing long-term cardiac morbidity when treated with PORT due to increased dose to LAD. PMID- 26837997 TI - Recurrent urinary tract infection masquerading as skeletal metastasis of hepatocellular carcinoma. PMID- 26837998 TI - Clinical outcome of primary non-metastatic breast cancer: A single institution experience. AB - BACKGROUND: We report on prognostic factors and long-term survival of non metastatic breast cancer patients treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre (SKMCH and RC) in Pakistan. MATERIALS AND METHODS: This retrospective cohort study is based on a review of 2829 pathologically confirmed non-metastatic breast cancer patients managed from January 1995 to May 2009. Median age was 45 years. Stage at presentation: Stage I (9%), stage II (59%), and stage III (32%). Infiltrating ductal carcinoma (92%) constituted the most prevalent histological subtype. Estrogen (ER), progesterone (PR) and Her2 neu were positive in 49%, 50%, and 26%, respectively. A mastectomy was performed in 67% and conservative surgery in 33% of the patients. Post-operative radiotherapy was delivered in 85% of the cases. Ninety percent of the patients received chemotherapy and mainly consisted of anthracycline-based regimens + taxanes. Hormonal manipulation was done in ER/PR positive patients. RESULTS: The 5- and 10-year overall survival (OS) was 70% (95% confidence interval [CI]: 68.2 71.8%) and 54% (95%CI: 51.2-56.8%), while disease free survival (DFS) was 65% (95% CI: 63-67%) and 52% (95% CI: 49.2-54.8%), respectively. Recurrence following primary treatment was seen in 35% of the patients. On multivariate analysis T stage, number of axillary nodal involvement, tumor grade, ER status and family history, were found to be independent predictors for OS and DFS. CONCLUSIONS: Over 90% of non-metastatic breast cancer patients present with stagesII and III disease and a significant proportion develop distant metastasis accounting for overall long-term outcome inferior to developed countries. Efforts should be directed to raise the level of health awareness and screening programs to improve early detection in Pakistan. PMID- 26837999 TI - A rare and unusual occurrence of rhabdomyosarcoma arising from the larynx. PMID- 26838000 TI - A study on biochemical facet of anemia in cancers: A strong link between erythropoietin and tumor necrosis factor alpha in anemic cancer patients. AB - BACKGROUND: The three direct factors that could lead cancer patients to anemia, apart from therapy are iron deficiency, inflammatory cytokines surge and decreased erythropoietin (Epo). Our aim was to quantify biochemical and hematologic markers serum Epo, ferritin (Fe) and tumor necrosis factor-alpha (TNF alpha) along with hemoglobin (Hb) to understand the associations between these factors, patient characteristics and anemia. MATERIALS AND METHODS: The study group consisted of 100 anemic cancer patients and 80 controls. Biochemical marker levels were determined by the enzyme linked immunosorbent assay on an autoanalyser. Univarient analysis, t-test, ANOVA, Bonferroni test, linear regression was performed to find correlations and associations among various factors. RESULTS: The baseline serum Epo (153.07 +/- 173.88 vs. 23.607 +/- 36.462) and Fe levels (233.53 +/- 257.12 vs. 23.06 +/- 20.04) were adequately high in cases compared with that controls (P <= 0.001). Considerable raise in TNF alpha levels was also observed (16.26 +/- 13.44 vs. 11.2375 +/- 4.84) (P = 0.001). TNF-alpha correlated positively (P = 0.022) with Epo and Fe (P = 0.000), which was also evident from large effect size of Epo (r2 = 0.414), TNF-alpha (r2 = 0.369), Hb (r2 = 0.226). Epo and Hb were negatively correlated (beta = -0.375, P = 0.001) and Epo production was found to be appropriate for the degree of anemia (O/P ratio of 3.51 +/- 1.26 vs. 1.43 +/- 0.47). A strong association was seen between Hb, Epo and TNF-alpha in hematological and gynecological malignancies for different grades of anemia. Men were more prone to life threatening anemia (13%) than women (9%). CONCLUSION: Anemia in cancers was not because of inadequate Epo or Fe levels, but because of improper Epo response. Further studies on molecular analysis of Epo, biochemical and molecular interplay between Epo and TNF-alpha could explain a rationale for anemia in cancers. PMID- 26838001 TI - Increasing cancer incidence in a tertiary care hospital in a developing country, India. AB - OBJECTIVE: Cancer is a major health problem in many countries including India. Since Cancer Registries are incomplete in India, only a few epidemiological studies have been done so far. The objective was to determine the leading causes of cancer in a tertiary care hospital and compare the incidences of different types of cancer with the incidences in India and developed countries. MATERIALS AND METHODS: An epidemiological study was done to collect data from pathology records of 1003 cancer cases during 6-month period in the year 2010. The data was collected in a computer and the data was utilized to make tables and histograms. RESULTS: Of the 1003 cases, the leading cancer site was breast, followed by colon and rectum, lymph node and stomach. The leading cancer site for men was colon and rectum and for women was breast. CONCLUSION: Cancer incidence is now low in India, a developing country, compared to developed Western countries. However, some cancers, like breast and colon and rectum cancers are increasing every year. IMPACT: The findings of this study support that cancer incidence is increasing in India and more epidemiological studies are needed. PMID- 26838002 TI - Display of health-risk warning on "arecanut sachets". PMID- 26838003 TI - A population-based screening program for early detection of common cancers among women in India - methodology and interim results. AB - BACKGROUND: Cancers of the uterine cervix, breast, and oral cavity accounted for 134,420, 115,251, and 24,375 cases, respectively, and were responsible for 52.8% of the total cancers among women in India in 2008. AIM: The major objectives were to create awareness regarding common cancers among women, to detect pre-cancers of the uterine cervix and oral cavity, and early cancers of the breast, uterine cervix, and oral cavity, by conducting screening with simple, low-cost technology, within the community, and to facilitate confirmation of diagnosis among the screen positives and treatment and follow-up among the diagnosed cases. SETTINGS AND METHODS: This is a community-based screening program for early detection of breast, uterine cervix, and oral cancers, being implemented among the socioeconomically disadvantaged women in Mumbai, India. The process involves selection of clusters, household surveys, health education, and screening the eligible women for breast, uterine cervix, and oral cancers, by primary healthcare workers, at a temporarily set-up clinic within the community. The program is planned to cover a 125,000 disadvantaged population in five years. RESULTS: Twenty-one thousand and fifteen people, with 4009 eligible women, have been covered to date. The compliance for screening for breast, cervix, and oral cavity has been 85, 70, and 88% and the screen positivity rates are 3.9, 14.9, and 3.9%, respectively. Twenty-seven oral pre-cancers, 25 cervix pre-cancers, one invasive cancer of the breast, two of the cervix, and one oral cavity cancer have been diagnosed among the screened women and all of them have complied with the treatment. CONCLUSIONS: The program is raising awareness about the common cancers and harms of tobacco among the disadvantaged women population in Mumbai. It is also helping in detecting pre-cancers and cancers among asymptomatic women and is assisting them in receiving treatment. PMID- 26838004 TI - Primary pure squamous cell carcinoma of the stomach treated with neoadjuvant chemotherapy and surgical resection. PMID- 26838005 TI - Family caregivers' burden: A hospital based study in 2010 among cancer patients from Delhi. AB - BACKGROUND: A large number of patients with chronic diseases like, cancer are cared for in homes by the family members in India. The vital role that these family members play as "caregivers" is well recognized, however, the burden on them is poorly understood. AIMS: To assess burden and to determine the predictors of burden on family caregivers of cancer patients. SETTING AND DESIGN: A cross sectional, hospital based study conducted in National Capital Territory of Delhi. MATERIALS AND METHODS: 200 family caregivers of cancer patients were selected by systematic random sampling and interviewed using standard, validated Hindi version of Zarit Burden Interview. STATISTICAL ANALYSIS: Univariate analysis and multivariable logistic regression were carried out using Statistical Package for the Social Sciences software (version 17.0). RESULTS: The study population consisted of 90 (45%) males and 110 (55%) female caregivers aged 18-65 years. 113 (56.5%) caregivers reported no or minimal burden while 75 (37.5%) caregivers reported mild to moderate burden. Using logistic regression marital status, education and type of family of caregivers, occupation of cancer patients and type of treatment facility were found to be the predictors of burden on caregivers. CONCLUSION: In view of the substantial burden on family caregivers coupled with lack of adequate number of cancer hospitals, there is a public health imperative to recognize this important group. All levels of health-staff in cancer hospitals in developing countries should be sensitized to the various burdens faced by family caregivers. PMID- 26838006 TI - Extranodal non: Hodgkin's lymphomain HIV. PMID- 26838007 TI - The cancer awareness assessment project: A small-scale survey across people with different levels of education in Mysore, India. AB - AIM: To assess the cancer awareness in respondents, their knowledge about the nature of cancer as a disease, its diagnosis and treatment, warning signs, environmental risk factors and conceptions of how risk factors work, as well as willingness to participate in screening programs if available. METHODOLOGY: Cancer awareness is an increasingly important issue in light of increasing incidence and associated healthcare costs, as well as the presence of risk management strategies. In this study, 453 people, drawn from several educational institutes/workplaces, were surveyed with respect to cancer awareness. The test sample included pre university students, undergraduates, and postgraduate students/workers. We checked for variations in cancer awareness across multiple educational levels to determine whether there was variation in levels of cancer awareness across educational classes. RESULTS: We found that confidence in perception of cancer awareness, and awareness itself, was not very high, and only postgraduates had a nuanced appreciation of some of the complexities of cancer epidemiology, and even then only moderately. CONCLUSION: The conclusions of the study point towards the need for optimal policymaking in the development of cancer awareness in the population. PMID- 26838008 TI - A case of tuberous sclerosis complex with bilateral advanced renal cell carcinoma. PMID- 26838009 TI - Patterns of care in geriatric cancer patients - An audit from a rural based hospital cancer registry in Kerala. AB - BACKGROUND: There is deficit of data from India on elderly patients with cancer. Comprehensive geriatric assessment may lead to a better decision making capacity in this population. However, routine implementation of such assessment is resource consuming. AIM: The aim of this study was to determine the patterns of care in elderly patients treated at a tertiary rural cancer center in India. MATERIALS AND METHODS: All patients with age 70 or above with solid tumors without any definitive treatment prior to the registration at our center and registered between 01/01/2010 and 31/12/2011 were selected for this study. The baseline demographic pattern and the pattern of care of treatment were analyzed. SPSS version 16 (IBM Inc, Armonk, New York, U.S.) was used for analysis. Descriptive data are provided. RESULTS: A total of 761 patients were evaluable subject to the aforementioned inclusion criteria. The median age of this cohort was 75 years (70-95 years). The most frequent primary sites of malignancies in 451 males were head neck (32.4%), lung (23.3%) and gastrointestinal (23.3%). In 310 females, the most common sites were head neck (31.6%), gynecological (18.4%) and gastrointestinal (24.5%). 228 (30%) of the patients had localized disease, 376 (49.4%) had loco-regionally advanced disease and 145 (19.1%) had distant metastases at presentation. 334 (46.32%) of patients were treated with curative intent. On logistic regression analysis the factors that predicted use of curative intent treatment were age <75 years, performance status 0-1, primary site and clinical extent of disease. CONCLUSION: Routine comprehensive geriatric assessment needs to be implemented in our setting as almost 50% of our geriatric patients undergo curative intent treatment. PMID- 26838010 TI - A rare case of recurrent intravenous leiomyomatosis: Role of GnRH analogues? PMID- 26838011 TI - One in 10 patients on antidepressants may have unrecognised bipolar disorder. PMID- 26838012 TI - Structures of seven molybdenum surfaces and their coverage dependent hydrogen adsorption. AB - Systematic density functional theory calculations and ab initio atomistic thermodynamics were applied to investigate the stability of seven metallic Mo surfaces [(110), (211), (111), (321), (310), (210) (100)] and their coverage dependent hydrogen adsorption. Only dissociative hydrogen adsorption is favored on these surfaces up to more than one monolayer saturation coverage. The computed hydrogen desorption temperatures on Mo(100) at 500 K and on Mo(110) at 410 K are in agreement with the available temperature-programmed desorption results. Under the consideration of H2 as the reduction reagent in Mo catalyst preparation, the computed surface morphology of Mo single crystal shows only exposed (110), (211) and (100) at high temperature; and the estimated surface proportion order of (110) > (211) > (100) agrees very well with the X-ray diffraction detected intensity order of (110) > (211) > (100). Surface reconstruction upon hydrogen adsorption has also been discussed. PMID- 26838013 TI - Conserved tyrosine 182 residue in hyperthermophilic esterase EstE1 plays a critical role in stabilizing the active site. AB - An aromatic amino acid, Tyr or Trp, located in the esterase active site wall, is highly conserved, with hyperthermophilic esterases showing preference for Tyr and lower temperature esterases showing preference for Trp. In this study, we investigated the role of Tyr(182) in the active site wall of hyperthermophilic esterase EstE1. Mutation of Tyr to Phe or Ala had a moderate effect on EstE1 thermal stability. However, a small-to-large mutation such as Tyr to His or Trp had a devastating effect on thermal stability. All mutant EstE1 enzymes showed reduced catalytic rates and enhanced substrate affinities as compared with wild type EstE1. Hydrogen bond formation involving Tyr(182) was unimportant for maintaining EstE1 thermal stability, as the EstE1 structure is already adapted to high temperatures via increased intramolecular interactions. However, removal of hydrogen bond from Tyr(182) significantly decreased EstE1 catalytic activity, suggesting its role in stabilization of the active site. These results suggest that Tyr is preferred over a similarly sized Phe residue or bulky His or Trp residue in the active site walls of hyperthermophilic esterases for stabilizing the active site and regulating catalytic activity at high temperatures. PMID- 26838015 TI - The transverse colon reconsider with respect to complete mesocolic excision and the greater omentum. PMID- 26838014 TI - Depletion of brain functional connectivity enhancement leads to disability progression in multiple sclerosis: A longitudinal resting-state fMRI study. AB - BACKGROUND: The compensatory effect of brain functional connectivity enhancement in relapsing-remitting multiple sclerosis (RRMS) remains controversial. OBJECTIVE: To characterize the relationships between brain functional connectivity changes and disability progression in RRMS. METHODS: Long-range connectivity, short-range connectivity, and density of connections were assessed using graph theoretical analysis of resting-state functional magnetic resonance imaging (fMRI) data acquired in 38 RRMS patients (disease duration: 120 +/- 32 months) and 24 controls. All subjects were explored at baseline and all patients and six controls 2 years later. RESULTS: At baseline, levels of long-range and short-range brain functional connectivity were higher in patients compared to controls. During the follow-up, decrease in connections' density was inversely correlated with disability progression. Post-hoc analysis evidenced differential evolution of brain functional connectivity metrics in patients according to their level of disability at baseline: while patients with lowest disability at baseline experienced an increase in all connectivity metrics during the follow up, patients with higher disability at baseline showed a decrease in the connectivity metrics. In these patients, decrease in the connectivity metrics was associated with disability progression. CONCLUSION: The study provides two main findings: (1) brain functional connectivity enhancement decreases during the disease course after reaching a maximal level, and (2) decrease in brain functional connectivity enhancement participates in disability progression. PMID- 26838017 TI - Letter to the editor: recurrent symptoms of gastrointestinal tract caused by isolated endometriosis in a middle-aged female. PMID- 26838016 TI - Malignancy is a risk factor for postoperative infectious complications after elective colorectal resection. AB - PURPOSE: Patient and technical factors influencing the postoperative infectious complications (ICs) after elective colorectal resections are satisfactorily described. However, the underlying disease-related factors have not been extensively evaluated. This study aimed to measure the effect of malignancy on postoperative surgical site and extra surgical site infections after elective colorectal resection. METHODS: This study is a bicentric retrospective matched pair study of prospectively gathered data. Between 2004 and 2013, 1104 consecutive patients underwent colorectal resection in two centers. Patients undergoing elective resection with supraperitoneal anastomosis for benign diseases (excluding inflammatory bowel disease) (group B, n = 305) were matched to randomly selected patients with malignancy (group M, n = 305). The matching variables were age, gender, American Society of Anesthesiologists (ASA) score, malnutrition, type of resection, and surgical approach. We compared the 30-day IC rates between patients with benign diseases (group B) and malignancy (group M). Multivariate logistic regression analysis was performed to identify the risk factors for ICs. RESULTS: Group M had a higher overall rate of IC (25.6 vs 16.1 %, P = 0.004) as well as a higher risk of extra surgical site infections (P = 0.007) and anastomotic leakage (P = 0.039). The independent risk factors for ICs were malignancy (odds ratio (OR) = 2.02; P = 0.002), age >=70 years (OR = 1.73, P = 0.018), tobacco history (OR = 1.87; P = 0.030), and obesity (OR = 1.68; P = 0.039). CONCLUSION: Malignancy, age, tobacco history, and obesity increase the risk of ICs after colorectal resection. Improvement of the modifiable risk factors, increased compliance with an enhanced recovery after surgery (ERAS) program in the overall population, and optimization of immune function in patients with malignancy should be considered. PMID- 26838018 TI - The Cobas(r) EGFR Mutation Test v2 assay. AB - Paul Brown speaks to Gemma Westcott, Commissioning Editor: Paul Brown has served as the Head of Roche Molecular Diagnostics at Roche Diagnostics Corporation since February 2010 having previously held a variety of positions within Roche Pharma. After completing his doctorate in organic chemistry he was awarded a post doctoral fellowship at the California Institute of Technology in Pasadena, CA, USA, but soon returned to his native UK to join Roche Pharma Research. Paul's first post within Roche was as group leader, doing drug discovery and making new small molecule drugs, but later moved into the business part of the company. Since then, he has enjoyed roles such as lifecycle leader for brands such as Tamiflu((r)) and Xenical, vice president of sales and marketing of the pharmaceutical division and most recently general manager of Roche Pharma, Sweden. PMID- 26838019 TI - Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: a Hoosier Cancer Research Network study. AB - PURPOSE: A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3 RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen. METHODS: GCT patients receiving a 5-day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3-RA days 1-5 (days 1, 3, and 5, if palonosetron) plus dexamethasone 20 mg days 1 and 2 and 4 mg po bid days 6, 7, and 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate-no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR > 27 %. RESULTS: Sixty-five patients were enrolled of whom 54 were eligible for analysis. Median age was 33. Fifty-one patients received bleomycin, etoposide, and cisplatin (BEP) chemotherapy. CR was observed in 13 (24.1 %) patients (95 % Agresti-Coull binomial C.I. 14.5 %, 37.1 %). CONCLUSION: The data in this phase II study, in contrast to our prior phase III study, appears to indicate a lower CR rate with the substitution of fosaprepitant for aprepitant. It is unknown whether the substitution of fosaprepitant for aprepitant provides the same benefit in multi-day cisplatin that was achieved with single-day cisplatin. Trial registration Clinical trial information NCT01736917. PMID- 26838020 TI - Use of olanzapine for the relief of nausea and vomiting in patients with advanced cancer: a multicenter survey in Japan. AB - Nausea and vomiting are among the most common and distressing symptoms in patients with advanced cancer. Olanzapine, an antipsychotic agent, is known to have an affinity for multiple neurotransmitter receptors. Previous studies have reported olanzapine to be efficacious in the treatment of nausea and vomiting. Although it has been administered at a number of facilities, its applicability to treat nausea and vomiting in patients with advanced cancer is poorly understood. We investigated the use of olanzapine for nausea and vomiting in patients with advanced cancer at multiple centers. This retrospective study was carried out at seven palliative care units and three facilities with palliative care teams in Japan from 2013 to 2015. The dosage of olanzapine, treatment duration, and duration from initial use until death were collected from the medical records. One hundred and eight patients met our inclusion criteria. The average dose of olanzapine was 3.6 mg (2.5 mg, n = 61; 5 mg, n = 46; 10 mg, n = 1) and average treatment duration was 18.7 days. The average duration from initial use until death was 39.0 days. There were no differences in the duration of administration until death between olanzapine doses (2.5 and 5 mg). Our results suggest that olanzapine have been used in patients with poor prognoses for nausea and vomiting in patients with advanced cancer. Conducting a prospective trial would further yield promising results. PMID- 26838021 TI - Quality of life discordance between terminal cancer patients and family caregivers: a multicenter study. AB - BACKGROUND: Research studies on quality of life (QOL) discordance between cancer patients and family caregivers are limited, and the results are inconsistent. The objective of this study was to examine QOL discordance between patients and family caregivers in a hospice setting and to identify factors associated with the discordance. METHODS: We enrolled 178 patient-family caregiver pairs from six tertiary hospital hospice palliative care units in South Korea in this cross sectional study. To establish groupings based on patient and family caregiver QOL levels, we measured the QOL of patient and family caregiver pairs using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 for Palliative Care and the Caregiver QOL Index-Cancer, respectively. Pairs were categorized into the following three groups: both good QOL pairs, only poor patient QOL, and only poor family caregiver QOL. Factors associated with only poor patient or only poor family caregiver QOL were compared to both good QOL pairs. A stepwise multivariate regression model was used to identify relevant factors. RESULTS: The QOL of family caregivers did not correlate significantly (P = 0.227) with QOL in terminally ill cancer patients. As well, poor emotional function in patients was the only significant factor associated with the only poor patient QOL group [adjusted odds ratio (aOR), 4.1; 95 % confidence interval (CI), 1.5-11.5]. However, emotionally distressed family caregivers (aOR, 10.2; 95 % CI, 2.8-37.5), family caregivers who professed a religion (aOR, 4.1; 95 % CI, 1.5-11.3), and family caregivers with low social support (aOR, 3.9; 95 % CI, 1.5-10.6) were independent predictors for the only poor family caregiver QOL group. CONCLUSIONS: Assessing the respective emotional status of both the patient and family caregiver is needed in hospice care to reduce the gap in QOL between the two groups. Further, more attention should be paid to the lack of social support for family caregivers. PMID- 26838022 TI - Linguistic validation of the Spanish version of the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). AB - PURPOSE: The U.S. NCI's PRO-CTCAE is a library of self-report items for assessing symptomatic adverse events in cancer clinical trials from the patient perspective. The aim of this study was to translate and linguistically validate a Spanish version. METHODS: PRO-CTCAE's 124 items were translated from English into Spanish using multiple forward and back translations. Native Spanish speakers undergoing cancer treatment were enrolled at six cancer treatment sites. Participants each completed approximately 50 items and were then interviewed using cognitive probes. The interviews were analyzed at the item level by linguistic themes, and responses were examined for evidence of equivalence to English. Items for which >=20 % of participants experienced difficulties were reviewed, and phrasing was revised and then retested in subsequent interviews. Items where <20 % of respondents experienced difficulties were also reviewed and were considered for rephrasing and retesting. RESULTS: One hundred nine participants from diverse Spanish-speaking countries were enrolled (77 in Round 1 and 32 in Round 2). A majority of items were well comprehended in Round 1. Two items presented difficulties in >=20 % of participants and were revised/retested without further difficulties. Two items presented difficulties in <20 %, and when retested exhibited no further difficulties. Two items presented difficulties in <20 %, but were not revised due to lack of alternatives. Sixteen items presented difficulties in <=12 % and were not revised because difficulties were minor. CONCLUSIONS: The Spanish PRO-CTCAE has been developed and refined for use in Spanish-speaking populations, with high levels of comprehension and equivalence to the English PRO-CTCAE. TRIAL REGISTRATION: ClinicalTrials.gov:NCT01436240. PMID- 26838023 TI - What happens after distress screening? Patterns of supportive care service utilization among oncology patients identified through a systematic screening protocol. AB - PURPOSE: While distress screening is important for identifying unmet needs of cancer patients, less is known about referral and uptake of supportive care services among distressed patients. The current analysis examined screen-based rates of referral to supportive care and explored demographic and clinical correlates of referral uptake. METHODS: We tracked distress screens completed by a varied group of cancer patients receiving outpatient care at a National Cancer Institute (NCI)-designated cancer center during a 1-month period. Electronic medical record review was used to examine the rates of supportive care referral and uptake among distressed patients. RESULTS: Out of 644 unique screens, 195 (30 %) patients reported significant distress; distressed patients were more likely to be non-white (odds ratio (OR) = 1.71, p < 0.01), prescribed psychiatric medication (OR = 1.92, p < 0.00), and have no previous contact with the cancer center's supportive care staff (OR = 1.62, p = 0.01). Thirty-four of these patients pre-emptively declined supportive care contact; thus, 161 were referred for supportive care. Among the 99 patients who received initial assessments by a team member, only 19 (19 %) requested and completed at least one follow-up appointment. CONCLUSIONS: Findings from this analysis support earlier work demonstrating significant supportive care needs in cancer patients. However, it challenges the assumption that screening will result in increased uptake of supportive care services beyond initial assessment. Further work should focus on facilitating engagement and reducing barriers for patients with continuing post assessment supportive care needs. PMID- 26838024 TI - Addressing fear of recurrence: improving psychological care in cancer survivors. AB - PURPOSE: Fear of cancer recurrence (FCR) is defined as "the fear or worry that the cancer will return or progress in the same area or another part of the body." FCR is associated with impaired functioning and lower quality of life in cancer patients. A cognitive-existential (CE) manualized group intervention for women with FCR showed a moderate effect size in reducing FCR, cancer-specific distress, and maladaptive coping. However, it appears that no individual intervention for FCR exists for both men and women. Therefore, the group intervention was adapted to an individual format. METHODS: This study was conducted to determine the feasibility, acceptability, and satisfaction of the individual intervention. The intervention was pilot-tested on n = 3 cancer survivors. The 6-week sessions included cognitive restructuring, structured exercises, and relaxation techniques. Participants completed questionnaire packages during a 4-week baseline period and throughout the 6-week intervention. Participants completed exit interviews following the intervention. RESULTS: General trends in baseline and intervention stages were compared. Based on the line graphs, the individual intervention appears to help survivors lower their elevated FCR and cancer specific distress. Qualitative exit interviews conducted with the study participants demonstrated that the intervention was acceptable and satisfactory. CONCLUSIONS: This clinical intervention allows researchers to systematically focus on evidence-based treatments for managing FCR, and displays the availability of treatment options in different therapeutic modalities. However, further research is needed to identify the active therapeutic ingredients and mechanisms of change in the intervention. Overall, intervention studies suggest it is possible to help cancer survivors manage their FCR. PMID- 26838025 TI - Use of complementary and alternative medicine by pediatric oncology patients during palliative care. AB - PURPOSE: Although the popularity of complementary and alternative medicine (CAM) has risen in the last decade, information about its use by pediatric patients in palliative care is still scarce. The purpose of the study was to assess the frequency and types of CAM administered by parents with children suffering from cancer during the palliative phase. METHODS: All parents who lost their child due to cancer in the federal state North Rhine Westfalia/Germany were eligible for the study. The first group of eligible parents was contacted in 1999-2000 and a second group of parents in 2005-2006. Upon agreement, parents were asked to complete a semi-structured questionnaire about the frequency of CAM use and the specific treatments that had been used. The types of CAM were categorized according to the National Center for Complementary and Alternative Medicine (NCCAM). RESULTS: A total of 96 parents participated in the study (48 in each cohort). Forty-three percent of all parents in both groups reported CAM use. The results show an increase of CAM use from 38 % in the first group to 49 % in the second cohort of pediatric patients during palliative care. The most common types of CAM used in both groups were homeopathy and treatment with mistletoe preparations. CONCLUSIONS: The study provides information about usage of CAM in children suffering from cancer during the palliative phase of the disease. Further research is required to investigate benefits, potential adverse effects, and the potential efficacy of CAM in this population. PMID- 26838026 TI - Decompressive percutaneous endoscopic gastrostomy in advanced cancer patients with small-bowel obstruction is feasible and effective: a large prospective study. AB - PURPOSE: The purpose of this study was to evaluate patient-centered outcomes of decompressive percutaneous endoscopic gastrostomy (dPEG) in patients with malignant bowel obstruction due to advanced gynecological and gastroenteric malignancies. METHODS: This is a prospective analysis of 158 consecutive patients with small-bowel obstruction from advanced gynecological and gastroenteric cancer who underwent PEG or percutaneous endoscopic jejunostomy (PEJ) positioning for decompressive purposes from 2002 to 2012. All of them had previous abdominal surgery and were unfit for any other surgical procedures. Symptom relief, procedural complications, and post dPEG palliation were assessed. Global Quality of Life (QoL) was evaluated in the last 2 years (25 consecutive patients) before and 7 days after dPEG placement using the Symptom Distress Scale (SDS). RESULTS: dPEG was successfully performed in 142 out of 158 patients (89.8 %). Failure of tube placement occurred in 16 patients (10.1 %). In 8/142 (5.6 %) patients, dPEG was guided by abdominal ultrasound. In 3/142 patients, dPEG was CT-guided. In 14 (9.8 %) patients, who had previously undergone total or subtotal gastrectomy, decompressive percutaneous endoscopic jejunostomy (dPEJ) was performed. In 1/14 patients, dPEJ was CT-guided. Out of 142 patients, 110 (77.4 %) experienced relief from nausea and vomiting 2 days after PEG. Out of 142 patients, 116 (81.6 %) were discharged. The median postoperative hospital stay was 9 days (range 3 60). Peristomal infection (14 %) and intermittent obstruction (8.4 %) were the most frequent complications associated with PEG. Median survival time was 57 days (range 4-472) after PEG placement. Twenty-five patients had QoL properly evaluated with SDS score before and 7 days after dPEG. Sixteen patients (64 %) out of 25 exhibited an improvement of QoL (p < 0.05), 7 (28 %) patients exhibited a non-significant worsening of QoL (p = 0.18), and in 2 (8 %) patients, it remained unmodified. CONCLUSIONS: dPEG is feasible, effective, relieves nausea and vomiting in patients with unremitting small-bowel obstruction from advanced gynecological and gastroenteric cancer, and improves QoL. PMID- 26838028 TI - Isolation and antiviral activity of water-soluble Cynomorium songaricum Rupr. polysaccharides. AB - The plant, Cynomorium songaricum Rupr., is used as a traditional medicine in China and Mongolia. In the present study, two new water-soluble polysaccharides isolated from C. songaricum Rupr. were purified by successive Sephadex G-75 and G 50 column chromatographies and then characterized by high resolution NMR and IR spectroscopies. The molecular weights of two polysaccharides were determined by an aqueous GPC to be [Formula: see text] = 3.7 * 10(4) and 1.0 * 10(4), respectively. In addition, it was found that the polysaccharide with the larger molecular weight was an acidic polysaccharide. It was found that the iodine starch reaction of both isolated polysaccharides was negative and the methylation analysis gave 2, 4, 6-tri-O-methyl alditol acetate as a main product. NMR and IR measurements and sugar analysis revealed that both polysaccharides had a (1 -> 3) alpha-d-glucopyranosidic main chain with a small number of branches. After sulfation, the sulfated C. songaricum Rupr. polysaccharides were found to have a potent inhibitory effect on HIV infection of MT-4 cells at a 50% effective concentration of 0.3-0.4 MUg/ml, a concentration that has almost the same high activity as standard dextran and curdlan sulfates, EC50 = 0.35 and 0.14 MUg/ml, respectively. The 50% cytotoxic concentration was low, CC50>1000 MUg/ml. In addition, the interaction between the sulfated polysaccharides and poly-l-lysine as a model protein compound was investigated by a surface plasmon resonance to reveal the anti-HIV mechanism. PMID- 26838027 TI - Multidisciplinary investigation links backward-speech trait and working memory through genetic mutation. AB - Case studies of unusual traits can provide unique snapshots of the effects of modified systems. In this study, we report on an individual from a Serbian family with the ability to rapidly, accurately and voluntarily speak backwards. We consider psychological, neural and genetic correlates of this trait to identify specific relevant neural mechanisms and new molecular pathways for working memory and speech-related tasks. EEG data suggest that the effect of word reversal precedes semantic integration of visually presented backward-words, and that event-related potentials above the frontal lobe are affected by both word reversal and the maintenance of backward-words in working memory. fMRI revealed that the left fusiform gyrus may facilitate the production of backward-speech. Exome sequencing identified three novel coding variants of potential significance in the RIC3, RIPK1 and ZBED5 genes. Taken together, our data suggest that, in this individual, the ability to speak backwards is afforded by an extraordinary working memory capacity. We hypothesise that this is served by cholinergic projections from the basal forebrain to the frontal cortex and supported by visual semantic loops within the left fusiform gyrus and that these neural processes may be mediated by a genetic mutation in RIC3; a chaperone for nicotinic acetylcholine receptors. PMID- 26838029 TI - Response to: 'Domestic use of bleach and infections in children: a multicentre cross-sectional study'. PMID- 26838030 TI - Complete loss of STAG2 expression is an indicator of good prognosis in patients with bladder cancer. AB - Stromal antigen 2 (STAG2) is an important member of cohesin, a conserved complex holding the sister chromatid together. Recent whole-genome sequencing studies have identified that genetic alterations of stag2 are common in bladder cancer (BC). The prognostic implications of STAG2 expression in BC remain unclear; we therefore analyzed its associations with the histopathological characteristics and clinical outcome in a Chinese population. We used immunohistochemistry assay to determine STAG2 protein expression in tumor tissues from 125 BC patients. STAG2 expression was analyzed according to clinicopathological features and patients' survival. Univariable and multivariable analyses were performed to identify predictors for recurrence-free survival (RFS) and cancer-specific survival (CSS). STAG2 expression was detected in 79.2 % of BC tissues, and 20.8 % of the tumor tissues had a complete loss of STAG2 protein expression. This STAG2 negative result was associated with a lower tumor histological grade with P = 0.009. The log-rank analysis revealed that the complete loss of STAG2 expression was associated with a lower risk of recurrence (P = 0.023) and a diminished risk of death (P = 0.034), especially in the subgroup of muscle-invasive BC (P = 0.043 for RFS and P = 0.087 for CSS). In multivariable Cox regression models, the loss of STAG2 expression remained a beneficial factor for RFS and CSS of BC patients. Univariate and multivariate analyses' results indicated that the complete loss of STAG2 expression was predictive for better RFS and CSS, suggesting its potential value as a prognostic biomarker. PMID- 26838032 TI - Neural Control of Blood Pressure in Chronic Intermittent Hypoxia. AB - Sleep apnea (SA) is increasing in prevalence and is commonly comorbid with hypertension. Chronic intermittent hypoxia is used to model the arterial hypoxemia seen in SA, and through this paradigm, the mechanisms that underlie SA induced hypertension are becoming clear. Cyclic hypoxic exposure during sleep chronically stimulates the carotid chemoreflexes, inducing sensory long-term facilitation, and drives sympathetic outflow from the hindbrain. The elevated sympathetic tone drives hypertension and renal sympathetic activity to the kidneys resulting in increased plasma renin activity and eventually angiotensin II (Ang II) peripherally. Upon waking, when respiration is normalized, the sympathetic activity does not diminish. This is partially because of adaptations leading to overactivation of the hindbrain regions controlling sympathetic outflow such as the nucleus tractus solitarius (NTS), and rostral ventrolateral medulla (RVLM). The sustained sympathetic activity is also due to enhanced synaptic signaling from the forebrain through the paraventricular nucleus (PVN). During the waking hours, when the chemoreceptors are not exposed to hypoxia, the forebrain circumventricular organs (CVOs) are stimulated by peripherally circulating Ang II from the elevated plasma renin activity. The CVOs and median preoptic nucleus chronically activate the PVN due to the Ang II signaling. All together, this leads to elevated nocturnal mean arterial pressure (MAP) as a response to hypoxemia, as well as inappropriately elevated diurnal MAP in response to maladaptations. PMID- 26838031 TI - Major Autonomic Neuroregulatory Pathways Underlying Short- and Long-Term Control of Cardiovascular Function. AB - Short-term and long-term blood pressure (BP) regulation and its maintenance at levels adequate to perfuse tissue organs involve an integrated action of multiple neural, cardiovascular, renal, endocrine and local tissue control systems. In the recent year, there has been a growing interest in the understanding of neural pathways key to BP control. For instance, through major advances in studies using both anesthetized and conscious animals, our knowledge of the essential neural mechanisms that subserve the baroreceptor, cardiopulmonary and chemoreceptor reflexes, and those evoked by the activation of stress pathways has dramatically increased. While the importance of these neural pathways in the maintenance of cardiovascular homeostasis is well established, the recognition of the central processing nuclei that integrate various afferent inputs to produce synchronous adjustments of autonomic outflows is still progressively expanding. Based on the literature provided thus far, the present review provides an overview in relation to the important neural determinants of BP control and later offers a concise description of major neuronal pathways that control autonomic outflows to the cardiovascular system in the short and long term. PMID- 26838033 TI - Aldosterone Production and Signaling Dysregulation in Obesity. AB - In the past decades, we have extended the view of aldosterone effects beyond epithelial tissues. New evidence regarding the aldosterone/mineralocorticoid receptor (MR) pathway in active metabolic tissues, including adipose tissue, has confirmed its pathogenic role in systemic inflammation, endothelial dysfunction, insulin resistance, and dyslipidemia. Obesity, a current epidemic worldwide, increases aldosterone production by several adipocyte factors such as leptin but is also associated with local aldosterone production. In addition, obesity can modulate MR activation leading to signaling dysregulation and a pro-inflammatory profile of adipocytes. Current knowledge have deciphered that this phenotypical differences of obesity may be explained, at least in part, by novel non-genomic activation of MR, new inducers of aldosterone synthesis, and probably by several epigenetic modifications. In addition, with the understanding of the complex interplay of obesity, hormones, and receptors, targeted pharmacological therapy is expected and is currently under active research. PMID- 26838034 TI - Strigolactones: new plant hormones in action. AB - MAIN CONCLUSION: The key step in the mode of action of strigolactones is the enzymatic detachment of the D-ring. The thus formed hydroxy butenolide induces conformational changes of the receptor pocket which trigger a cascade of reactions in the signal transduction. Strigolactones (SLs) constitute a new class of plant hormones which are of increasing importance in plant science. For the last 60 years, they have been known as germination stimulants for parasitic plants. Recently, several new bio-properties of SLs have been discovered such as the branching factor for arbuscular mycorrhizal fungi, regulation of plant architecture (inhibition of bud outgrowth and of shoot branching) and the response to abiotic factors, etc. To broaden horizons and encourage new ideas for identifying and synthesising new and structurally simple SLs, this review is focused on molecular aspects of this new class of plant hormones. Special attention has been given to structural features, the mode of action of these phytohormones in various biological actions, the design of SL analogs and their applications. PMID- 26838036 TI - Characterizing tissue stiffness at the tip of a rigid needle using an opto mechanical force sensor. AB - We present a novel device that allows the user to measure the Young Modulus of a material at the opening of a 5 mm diameter needle. The device relies on a miniaturized cantilever spring mounted at the end of the needle and interrogated via Fabry-Perot optical fiber interferometry. The probe is repetitively brought in and out of contact with the sample at the end of the needle by means of a steel cable that is controlled via a piezoelectric actuator located at the proximal end. We demonstrate the ability of our device to detect and quantify layers of varying stiffness during needle insertion in a gelatin phantom and to successfully locate tissue boundaries in bovine liver tissue embedded in gelatin. PMID- 26838035 TI - Spatial isolation and environmental factors drive distinct bacterial and archaeal communities in different types of petroleum reservoirs in China. AB - To investigate the spatial distribution of microbial communities and their drivers in petroleum reservoir environments, we performed pyrosequencing of microbial partial 16S rRNA, derived from 20 geographically separated water flooding reservoirs, and two reservoirs that had not been flooded, in China. The results indicated that distinct underground microbial communities inhabited the different reservoirs. Compared with the bacteria, archaeal alpha-diversity was not strongly correlated with the environmental variables. The variation of the bacterial and archaeal community compositions was affected synthetically, by the mining patterns, spatial isolation, reservoir temperature, salinity and pH of the formation brine. The environmental factors explained 64.22% and 78.26% of the total variance for the bacterial and archaeal communities, respectively. Despite the diverse community compositions, shared populations (48 bacterial and 18 archaeal genera) were found and were dominant in most of the oilfields. Potential indigenous microorganisms, including Carboxydibrachium, Thermosinus, and Neptunomonas, were only detected in a reservoir that had not been flooded with water. This study indicates that: 1) the environmental variation drives distinct microbial communities in different reservoirs; 2) compared with the archaea, the bacterial communities were highly heterogeneous within and among the reservoirs; and 3) despite the community variation, some microorganisms are dominant in multiple petroleum reservoirs. PMID- 26838037 TI - A torso model comparison of temperature preservation devices for use in the prehospital environment. AB - BACKGROUND: Hypothermia is an independent predictor of increased morbidity and mortality in patients with trauma. Several strategies and products have been developed to minimise patients' heat loss in the prehospital arena, but there is little evidence to inform the clinician concerning their effectiveness. METHODS: We used a human torso model consisting of two 5.5-litre fluid bags to simultaneously compare four passive (space blanket, bubble wrap, Blizzard blanket, ambulance blanket) and one active (Ready-Heat II blanket) temperature preservation products. A torso model without any temperature preservation device provided a control. For each test, the torso models were warmed to 37 degrees C and left outdoors. Core temperatures were recorded every 10 min for 1 h in total; tests were repeated 10 times. RESULTS: A significant difference in temperature was detected among groups at 30 and 60 min (F (1.29, 10.30)=103.58, p<0.001 and F (1.64, 14.78)=163.28, p<0.001, respectively). Mean temperature reductions (95% CI) after 1 h of environmental exposure were the following: 11.6 (10.3 to 12.9) degrees C in control group, 4.5 (3.9 to 5.1) degrees C in space blanket group, 3.6 (3 to 4.3) degrees C in bubble-wrap group, 2.1 (1.7 to 2.5) degrees C in Blizzard blanket group, 6.1 (5.8 to 6.5) degrees C in ambulance blanket group and 1.1 (0.7 to 1.6) degrees C in Ready-Heat II blanket group. CONCLUSIONS: In this study, using a torso model based on two 5 L dialysate bags we found the Ready-Heat II heating blanket and Blizzard blanket were associated with lower rates of heat loss after 60 min environmental exposure than the other devices tested. PMID- 26838038 TI - Citric acid- and Tween((r)) 80-assisted phytoremediation of a co-contaminated soil: alfalfa (Medicago sativa L.) performance and remediation potential. AB - A pot experiment was designed to assess the phytoremediation potential of alfalfa (Medicago sativa L.) in a co-contaminated (i.e., heavy metals and petroleum hydrocarbons) soil and the influence of citric acid and Tween((r)) 80 (polyethylene glycol sorbitan monooleate), applied individually and combined together, for their possible use in chemically assisted phytoremediation. The results showed that alfalfa plants could tolerate and grow in a co-contaminated soil. Over a 90-day experimental time, shoot and root biomass increased and negligible plant mortality occurred. Heavy metals were uptaken by alfalfa to a limited extent, mostly by plant roots, and their concentration in plant tissues were in the following order: Zn > Cu > Pb. Microbial population (alkane-degrading microorganisms) and activity (lipase enzyme) were enhanced in the presence of alfalfa with rhizosphere effects of 9.1 and 1.5, respectively, after 90 days. Soil amendments did not significantly enhance plant metal concentration or total uptake. In contrast, the combination of citric acid and Tween((r)) 80 significantly improved alkane-degrading microorganisms (2.4-fold increase) and lipase activity (5.3-fold increase) in the rhizosphere of amended plants, after 30 days of experiment. This evidence supports a favorable response of alfalfa in terms of tolerance to a co-contaminated soil and improvement of rhizosphere microbial number and activity, additionally enhanced by the joint application of citric acid and Tween((r)) 80, which could be promising for future phytoremediation applications. PMID- 26838039 TI - Arsenic contamination of groundwater and its induced health effects in Shahpur block, Bhojpur district, Bihar state, India: risk evaluation. AB - The objective of this study was to determine the magnitude of groundwater arsenic contamination in Shahpur block of Bhojpur district, Bihar state, India and its health effects such as dermal, neurological, obstetric effects, and cancer risk. The School of Environmental Studies (SOES) collected 4704 tube-well water samples from all 88 villages of Shahpur, which were analyzed for arsenic. We found 40.3 and 21.1 % of the tube-wells had arsenic above 10 and 50 MUg/l, respectively, with maximum concentration of 1805 MUg/l. The study shows that 75,000, 39,000, and 10,000 people could be exposed to arsenic-contaminated water greater than 10, 50, and 300 MUg/l, respectively. Our medical team examined 1422 villagers from Shahpur and registered 161 (prevalence rate, 11.3 %) with arsenical skin lesions. Arsenical skin lesions were also observed in 29 children of 525 screened. We analyzed 579 biological samples (hair, nail, and urine) from Shahpur and found that 82, 89, and 91 % of hair, nail, and urine, respectively, had arsenic above the normal levels, indicating many people in the study area are sub-clinically affected. Arsenical neuropathy was observed in 48 % of 102 arsenicosis patients. The study also found that arsenic exposed women with severe skin lesions had adversely affected their pregnancies. The carcinogenic and non-carcinogenic risks were also estimated based on the generated data. Safe drinking water supply is urgently required to combat arsenic situation in affected villages of Shahpur. PMID- 26838041 TI - Toxicity of wood smoke particles in human A549 lung epithelial cells: the role of PAHs, soot and zinc. AB - Indoor air pollution is associated with increased morbidity and mortality. Specifically, the health impact of emissions from domestic burning of biomass and coal is most relevant and is estimated to contribute to over 4 million premature deaths per year worldwide. Wood is the main fuel source for biomass combustion and the shift towards renewable energy sources will further increase emissions from wood combustion even in developed countries. However, little is known about the constituents of wood smoke and biological mechanisms that are responsible for adverse health effects. We exposed A549 lung epithelial cells to collected wood smoke particles and found an increase in cellular reactive oxygen species as well as a response to bioavailable polycyclic aromatic hydrocarbons. In contrast, cell vitality and regulation of the pro-inflammatory cytokine interleukin-8 were not affected. Using a candidate approach, we could recapitulate WSP toxicity by the combined actions of its constituents soot, metals and PAHs. The soot fraction and metals were found to be the most important factors for ROS formation, whereas the PAH response can be mimicked by the model PAH benzo[a]pyrene. Strikingly, PAHs adsorbed to WSPs were even more potent in activating target gene expression than B[a]P individually applied in suspension. As PAHs initiate multiple adverse outcome pathways and are prominent carcinogens, their role as key pollutants in wood smoke and its health effects warrants further investigation. The presented results suggest that each of the investigated constituents soot, metals and PAHs are major contributors to WSP toxicity. Mitigation strategies to prevent adverse health effects of wood combustion should therefore not only aim at reducing the emitted soot and PAHs but also the metal content, through the use of more efficient combustion appliances, and particle precipitation techniques, respectively. PMID- 26838040 TI - Common and rare variants associating with serum levels of creatine kinase and lactate dehydrogenase. AB - Creatine kinase (CK) and lactate dehydrogenase (LDH) are widely used markers of tissue damage. To search for sequence variants influencing serum levels of CK and LDH, 28.3 million sequence variants identified through whole-genome sequencing of 2,636 Icelanders were imputed into 63,159 and 98,585 people with CK and LDH measurements, respectively. Here we describe 13 variants associating with serum CK and 16 with LDH levels, including four that associate with both. Among those, 15 are non-synonymous variants and 12 have a minor allele frequency below 5%. We report sequence variants in genes encoding the enzymes being measured (CKM and LDHA), as well as in genes linked to muscular (ANO5) and immune/inflammatory function (CD163/CD163L1, CSF1, CFH, HLA-DQB1, LILRB5, NINJ1 and STAB1). A number of the genes are linked to the mononuclear/phagocyte system and clearance of enzymes from the serum. This highlights the variety in the sources of normal diversity in serum levels of enzymes. PMID- 26838042 TI - Phase II metabolism of the soy isoflavones genistein and daidzein in humans, rats and mice: a cross-species and sex comparison. AB - Soy isoflavones (IF) are in the focus of biomedical research since more than two decades. To assess their bioactivity, IF are investigated in rats and mice as a model. As the biological activity of IF is affected by their biotransformation, our aim was to comprehensively compare the conjugative and microbial metabolism of daidzein and genistein in adult humans, rats and mice of both sexes. One identical soy extract and a validated LC-MS method were used for all studies. We detected considerable differences between the three species. In rats and mice, sex-specific differences were observed in addition. The major plasma phase II metabolites in humans were the 7-sulfo-4'-glucuronides (39-49 %) and, in case of genistein, also the diglucuronide (34 %), whereas in mice monosulfates (33-41 %) and monoglucuronides (30-40 %) predominated. In male rats the disulfates (23-62 %) and 7-sulfo-4'-glucuronides (19-54 %) were predominant, while in female rats the 7-glucuronides (81-93 %) exhibited highest concentrations. The portion of aglycones was low in humans (0.5-1.3 %) and rats (0.5-3.1 %) but comparatively high in mice (3.1-26.0 %), especially in the case of daidzein. Furthermore, substantial differences were observed between daidzein and genistein metabolism. In contrast to humans, all rats and mice were equol producer, independent of their sex. In conclusion, there are marked differences between humans, rats and mice in the profile of major metabolites following IF phase II metabolism. These differences may contribute to resolve inconsistencies in results concerning the bioactivity of IF and should be considered when applying findings of animal studies to humans, e.g., for risk assessment. PMID- 26838044 TI - Butyrylcholinesterase identification in a phenylvalerate esterase-enriched fraction sensitive to low mipafox concentrations in chicken brain. AB - Multiple epidemiological and experimental studies have demonstrated that exposure to organophosphorus compounds (OPs) is associated with a variety of neurological disorders. Some of these exposure symptoms cannot be precisely correlated with known molecular targets and mechanisms of toxicity. Most of the known molecular targets of OPs fall in the protein family of serine esterases. We have shown that three esterase components in the soluble fraction of chicken brain (an animal model frequently used in OP neurotoxicity assays) can be kinetically distinguished using paraoxon, mipafox and phenylmethyl sulfonyl fluoride as inhibitors, and phenyl valerate as a substrate; we termed them Ealpha, Ebeta and Egamma. The Ealpha-component, which is highly sensitive to paraoxon and mipafox and resistant to PMSF, has shown sensitivity to the substrate acetylthiocholine, and to ethopropazine and iso-OMPA (specific inhibitors of butyrylcholinesterase; BChE) but not to BW 284C51 (a specific inhibitor of acetylcholinesterase; AChE). In this work, we employed a large-scale proteomic analysis B with a LC/MS/MS TripleTOF system; 259 proteins were identified in a chromatographic fractionated sample enriched in Ealpha activity of the chicken brain soluble fraction. Bioinformatics analysis revealed that BChE is the only candidate protein identified to be responsible for almost all the Ealpha activity. This study demonstrates the potential information to be gained from combining kinetic dissection with large-scale proteomics and bioinformatics analyses for identification of proteins that are targets of OP toxicity and may be involved in detoxification of phosphoryl and carbonyl esters. PMID- 26838043 TI - Genetic enhancement of microsomal epoxide hydrolase improves metabolic detoxification but impairs cerebral blood flow regulation. AB - Microsomal epoxide hydrolase (mEH) is a detoxifying enzyme for xenobiotic compounds. Enzymatic activity of mEH can be greatly increased by a point mutation, leading to an E404D amino acid exchange in its catalytic triad. Surprisingly, this variant is not found in any vertebrate species, despite the obvious advantage of accelerated detoxification. We hypothesized that this evolutionary avoidance is due to the fact that the mEH plays a dualistic role in detoxification and control of endogenous vascular signaling molecules. To test this, we generated mEH E404D mice and assessed them for detoxification capacity and vascular dynamics. In liver microsomes from these mice, turnover of the xenobiotic compound phenanthrene-9,10-oxide was four times faster compared to WT liver microsomes, confirming accelerated detoxification. mEH E404D animals also showed faster metabolization of a specific class of endogenous eicosanoids, arachidonic acid-derived epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs). Significantly higher DHETs/EETs ratios were found in mEH E404D liver, urine, plasma, brain and cerebral endothelial cells compared to WT controls, suggesting a broad impact of the mEH mutant on endogenous EETs metabolism. Because EETs are strong vasodilators in cerebral vasculature, hemodynamics were assessed in mEH E404D and WT cerebral cortex and hippocampus using cerebral blood volume (CBV)-based functional magnetic resonance imaging (fMRI). Basal CBV0 levels were similar between mEH E404D and control mice in both brain areas. But vascular reactivity and vasodilation in response to the vasodilatory drug acetazolamide were reduced in mEH E404D forebrain compared to WT controls by factor 3 and 2.6, respectively. These results demonstrate a critical role for mEH E404D in vasodynamics and suggest that deregulation of endogenous signaling pathways is the undesirable gain of function associated with the E404D variant. PMID- 26838045 TI - PPARalpha-dependent cholesterol/testosterone disruption in Leydig cells mediates 2,4-dichlorophenoxyacetic acid-induced testicular toxicity in mice. AB - It was reported that 2,4-dichlorophenoxyacetic acid (2,4-D), a commonly used herbicide and a possible endocrine disruptor, can disturb spermatogenesis, but the precise mechanism is not understood. Since 2,4-D is a weak peroxisome proliferator in hepatocytes and peroxisome proliferator-activated receptor alpha (PPARalpha) is also expressed in Leydig cells, this study aimed to investigate the link between PPARalpha and 2,4-D-mediated testicular dysfunction. 2,4-D (130 mg/kg/day) was administered to wild-type and Ppara-null mice for 2 weeks, and the alterations in testis and testosterone/cholesterol metabolism in Leydig cells were examined. Treatment with 2,4-D markedly decreased testicular testosterone in wild-type mice, leading to degeneration of spermatocytes and Sertoli cells. The 2,4-D decreased cholesterol levels in Leydig cells of wild-type mice through down regulating the expression of 3-hydroxy-3-methylglutaryl coenzyme A synthase 1 and reductase, involved in de novo cholesterogenesis. However, the mRNAs encoding the important proteins involved in testosterone synthesis were unchanged by 2,4-D except for CYP17A1, indicating that exhausted cholesterol levels in the cells is a main reason for reduced testicular testosterone. Additionally, pregnancy rate and the number of pups between 2,4-D-treated wild-type male mice and untreated female mice were significantly lower compared with those between untreated couples. These phenomena were not observed in 2,4-D-treated Ppara-null males. Collectively, these results suggest a critical role for PPARalpha in 2,4-D induced testicular toxicity due to disruption of cholesterol/testosterone homeostasis in Leydig cells. This study yields novel insights into the possible mechanism of testicular dysfunction and male infertility caused by 2,4-D. PMID- 26838046 TI - Tumor promotion and inhibition by phenobarbital in livers of conditional Apc deficient mice. AB - Activation of Wnt/beta-catenin signaling is important for human and rodent hepatocarcinogenesis. In mice, the tumor promoter phenobarbital (PB) selects for hepatocellular tumors with activating beta-catenin mutations via constitutive androstane receptor activation. PB-dependent tumor promotion was studied in mice with genetic inactivation of Apc, a negative regulator of beta-catenin, to circumvent the problem of randomly induced mutations by chemical initiators and to allow monitoring of PB- and Wnt/beta-catenin-dependent tumorigenesis in the absence of unknown genomic alterations. Moreover, the study was designed to investigate PB-induced proliferation of liver cells with activated beta-catenin. PB treatment provided Apc-deficient hepatocytes with only a minor proliferative advantage, and additional connexin 32 deficiency did not affect the proliferative response. PB significantly promoted the outgrowth of Apc-deficient hepatocellular adenoma (HCA), but simultaneously inhibited the formation of Apc-deficient hepatocellular carcinoma (HCC). The probability of tumor promotion by PB was calculated to be much lower for hepatocytes with loss of Apc, as compared to mutational beta-catenin activation. Comprehensive transcriptomic and phosphoproteomic characterization of HCA and HCC revealed molecular details of the two tumor types. HCC were characterized by a loss of differentiated hepatocellular gene expression, enhanced proliferative signaling, and massive over-activation of Wnt/beta-catenin signaling. In conclusion, PB exerts a dual role in liver tumor formation by promoting the growth of HCA but inhibiting the growth of HCC. Data demonstrate that one and the same compound can produce opposite effects on hepatocarcinogenesis, depending on context, highlighting the necessity to develop a more differentiated view on the tumorigenicity of this model compound. PMID- 26838047 TI - From bisphenol A to bisphenol F and a ban of mustard due to chronic low-dose exposures? PMID- 26838048 TI - Prevention of SHIV transmission by topical IFN-beta treatment. AB - Understanding vaginal and rectal HIV transmission and protective cellular and molecular mechanisms is critical for designing new prevention strategies, including those required for an effective vaccine. The determinants of protection against HIV infection are, however, poorly understood. Increasing evidence suggest that innate immune defenses may help protect mucosal surfaces from HIV transmission in highly exposed, uninfected subjects. More recent studies suggest that systemically administered type 1 interferon protects against simian immunodeficiency virus infection of macaques. Here we hypothesized that topically applied type 1 interferons might stimulate vaginal innate responses that could protect against HIV transmission. We therefore applied a recombinant human type 1 interferon (IFN-beta) to the vagina of rhesus macaques and vaginally challenged them with pathogenic simian/human immunodeficiency virus (SHIV). Vaginal administration of IFN-beta resulted in marked local changes in immune cell phenotype, increasing immune activation and HIV co-receptor expression, yet provided significant protection from SHIV acquisition as interferon response genes were also upregulated. These data suggest that protection from vaginal HIV acquisition may be achieved by activating innate mucosal defenses. PMID- 26838049 TI - KLF6 contributes to myeloid cell plasticity in the pathogenesis of intestinal inflammation. AB - Inflammatory bowel disease (IBD) is associated with dysregulated macrophage responses, such that quiescent macrophages acquire a pro-inflammatory activation state and contribute to chronic intestinal inflammation. The transcriptional events governing macrophage activation and gene expression in the context of chronic inflammation such as IBD remain incompletely understood. Here, we identify Kruppel-like transcription factor-6 (KLF6) as a critical regulator of pathogenic myeloid cell activation in human and experimental IBD. We found that KLF6 was significantly upregulated in myeloid cells and intestinal tissue from IBD patients and experimental models of IBD, particularly in actively inflamed regions of the colon. Using complementary gain- and loss-of-function studies, we observed that KLF6 promotes pro-inflammatory gene expression through enhancement of nuclear factor kappaB (NFkappaB) signaling, while simultaneously suppressing anti-inflammatory gene expression through repression of signal transducer and activator of transcription 3 (STAT3) signaling. To study the in vivo role of myeloid KLF6, we treated myeloid-specific KLF6-knockout mice (Mac-KLF6-KO) with dextran sulfate sodium (DSS) and found that Mac-KLF6-KO mice were protected against chemically-induced colitis; this highlights the central role of myeloid KLF6 in promoting intestinal inflammation. Collectively, our results point to a novel gene regulatory program underlying pathogenic, pro-inflammatory macrophage activation in the setting of chronic intestinal inflammation. PMID- 26838050 TI - AIM2 contributes to the maintenance of intestinal integrity via Akt and protects against Salmonella mucosal infection. AB - The mechanism regulating the gastrointestinal epithelial barrier remains poorly understood. We herein demonstrate that Absent in melanoma-2 (AIM2) contributes to the maintenance of intestinal barrier integrity and defense against bacterial infection. AIM2-deficient mice displayed an increased susceptibility to mucosal but not systemic infection by Salmonella typhimurium, indicating a protective role for AIM2 in the gastrointestinal tract. In a Salmonella colitis model, compared with wild-type mice, AIM2(-/-) mice exhibited more severe body weight loss, intestinal damage, intestinal inflammation, and disruption of basal and activated epithelial cell turnover. In vivo and in vitro data showed that AIM2 restricted the early epithelial paracellular invasion of Salmonella and decreased epithelial permeability. The decreased epithelial barrier in AIM2(-/-) mice might be attributed to the altered expression of tight junction proteins that contribute to epithelial integrity. AIM2 promoted the expression of tight junction proteins through Akt activation. Together, these results suggest that AIM2 is required for maintaining the integrity of the epithelial barrier. PMID- 26838051 TI - TCR sequencing of single cells reactive to DQ2.5-glia-alpha2 and DQ2.5-glia omega2 reveals clonal expansion and epitope-specific V-gene usage. AB - CD4+ T cells recognizing dietary gluten epitopes in the context of disease associated human leukocyte antigen (HLA)-DQ2 or HLA-DQ8 molecules are the key players in celiac disease pathogenesis. Here, we conducted a large-scale single cell paired T-cell receptor (TCR) sequencing study to characterize the TCR repertoire for two homologous immunodominant gluten epitopes, DQ2.5-glia-alpha2 and DQ2.5-glia-omega2, in blood of celiac disease patients after oral gluten challenge. Despite sequence similarity of the epitopes, the TCR repertoires are unique but shared several overall features. We demonstrate that clonally expanded T cells dominate the T-cell responses to both epitopes. Moreover, we find V-gene bias of TRAV26, TRAV4, and TRBV7 in DQ2.5-glia-alpha2 reactive TCRs, while DQ2.5 glia-omega2 TCRs displayed significant bias toward TRAV4 and TRBV4. The knowledge that antigen-specific TCR repertoire in chronic inflammatory diseases tends to be dominated by a few expanded clones that use the same TCR V-gene segments across patients is important information for HLA-associated diseases where the antigen is unknown. PMID- 26838053 TI - Global Warming Attenuates the Tropical Atlantic-Pacific Teleconnection. AB - Changes in global sea surface temperature (SST) since the end of last century display a pattern of widespread warming intercepted by cooling in the eastern equatorial Pacific and western coasts of the American continent. Studies have suggested that the cooling in the eastern equatorial Pacific may be partly induced by warming in the North Atlantic. However, it remains unknown how stable this inter-tropical teleconnection will be under global warming. Here we show that the inter-tropical teleconnection from the tropical Atlantic to Pacific weakens substantially as the CO2 concentration increases. This reduced impact is related to the El Nino-like warming of the tropical Pacific mean state, which leads to limited seasonal migration of the Pacific inter-tropical convergence zone (ITCZ) and weakened ocean heat transport. A fast decay of the tropical Atlantic SST anomalies in a warmer climate also contributes to the weakened teleconnection. Our study suggests that as greenhouse warming continues, the trend in the tropical Pacific as well as the development of ENSO will be less frequently interrupted by the Atlantic because of this attenuation. The weakened teleconnection is also supported by CMIP5 models, although only a few of these models can capture this inter-tropical teleconnection. PMID- 26838052 TI - Host innate inflammatory factors and staphylococcal protein A influence the duration of human Staphylococcus aureus nasal carriage. AB - Human Staphylococcus aureus (SA) nasal carriage provides a reservoir for the dissemination of infectious strains; however, factors regulating the establishment and persistence of nasal colonization are mostly unknown. We measured carriage duration and nasal fluid inflammatory markers after nasally inoculating healthy participants with their previously isolated SA strains. Out of 15 studies, 10 resulted in rapid clearance (9+/-6 days) that corresponded with upregulated chemokines, growth factors, and predominantly Th1-type cytokines, but not interleukin (IL)-17. Nasal SA persistence corresponded with elevated baseline levels of macrophage inflammatory protein-1beta, IL-1beta, and IL-6, no induction of inflammatory factors after inoculation, and decreased IL-1 receptor antagonist/IL-1beta ratio. SA-expressed staphylococcal protein A (SpA) levels correlated positively with carriage duration. Competitive inoculation studies revealed that isogenic SpA knockout (DeltaSpA) strains were cleared faster than wild type only in participants with upregulated inflammatory markers after inoculation. The remaining participants did not mount an inflammatory response and did not clear either strain. DeltaSpA strains demonstrated lower growth rates in carrier nasal fluids and lower survival rates when incubated with neutrophils. Collectively, the presented studies identify innate immune effectors that cooperatively modulate nasal carriage duration, and confirm SpA as a bacterial codeterminant of SA nasal carriage. PMID- 26838055 TI - Internal structure of cesium-bearing radioactive microparticles released from Fukushima nuclear power plant. AB - Microparticles containing substantial amounts of radiocesium collected from the ground in Fukushima were investigated mainly by transmission electron microscopy (TEM) and X-ray microanalysis with scanning TEM (STEM). Particles of around 2 MUm in diameter are basically silicate glass containing Fe and Zn as transition metals, Cs, Rb and K as alkali ions, and Sn as substantial elements. These elements are homogeneously distributed in the glass except Cs which has a concentration gradient, increasing from center to surface. Nano-sized crystallites such as copper- zinc- and molybdenum sulfide, and silver telluride were found inside the microparticles, which probably resulted from the segregation of the silicate and sulfide (telluride) during molten-stage. An alkali-depleted layer of ca. 0.2 MUm thick exists at the outer side of the particle collected from cedar leaves 8 months after the nuclear accident, suggesting gradual leaching of radiocesium from the microparticles in the natural environment. PMID- 26838054 TI - Association between a Healthy Lifestyle Score and inflammatory markers among Puerto Rican adults. AB - BACKGROUND AND AIMS: The relationship between multiple lifestyle components analyzed in combination and inflammation remains understudied. We aimed to assess the association between a Healthy Lifestyle Score (HLS) that includes adherence to five behavioral components (diet, physical activity and sedentary behaviors, smoking, social support and network, and sleep) and inflammatory markers, as well as the role of the HLS in inflammation among individuals with cardiometabolic conditions, in Puerto Rican adults. METHODS AND RESULTS: In a cross-sectional study of 842 Puerto Ricans adults (aged 45-75 y) living in Boston, MA, the HLS (range = 0-190; maximum indicative of healthiest adherence) was analyzed for association with three inflammatory markers: interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). In multivariable-adjusted models, the HLS was inversely associated with IL-6 (beta +/- SE = -0.55 +/- 0.13; P < 0.001) and TNF-alpha (-0.39 +/- 0.13; P = 0.004). The dietary and smoking components were associated with both inflammatory markers independently of the other HLS components. Significant inverse associations were observed for each 20 unit increase in HLS and IL-6 and TNF-alpha for participants with hypertension (n = 600; beta +/- SE = -0.58 +/- 0.16; -0.46 +/- 0.16, respectively) and with overweight/obesity (n = 743; beta +/- SE = -0.59 +/- 0.13; -0.50 +/- 0.14, respectively), but not for those with diabetes (n = 187) or heart disease (n = 192). The HLS was not associated with CRP, after adjustment for potential confounders. CONCLUSION: Higher adherence to multiple lifestyle behaviors was associated with lower concentrations of inflammatory markers. Because low-grade inflammation may precede chronic diseases, following an overall healthy lifestyle may help lower risk of these diseases. PMID- 26838056 TI - Rapid intensification and the bimodal distribution of tropical cyclone intensity. AB - The severity of a tropical cyclone (TC) is often summarized by its lifetime maximum intensity (LMI), and the climatological LMI distribution is a fundamental feature of the climate system. The distinctive bimodality of the LMI distribution means that major storms (LMI >96 kt) are not very rare compared with less intense storms. Rapid intensification (RI) is the dramatic strengthening of a TC in a short time, and is notoriously difficult to forecast or simulate. Here we show that the bimodality of the LMI distribution reflects two types of storms: those that undergo RI during their lifetime (RI storms) and those that do not (non-RI storms). The vast majority (79%) of major storms are RI storms. Few non-RI storms (6%) become major storms. While the importance of RI has been recognized in weather forecasting, our results demonstrate that RI also plays a crucial role in the TC climatology. PMID- 26838057 TI - Degree of Anticoagulation Control in Patients With Atrial Fibrillation in Spain: Need to Minimize Biases and Contextualize Results. Response Barrios et al. PMID- 26838058 TI - Sensationalist Headlines: Also in the Scientific Press? Response by Ferreira Gonzalez. PMID- 26838059 TI - Sensationalist Headlines: Also in the Scientific Press? PMID- 26838060 TI - Degree of Anticoagulation Control in Patients With Atrial Fibrillation in Spain: Need to Minimize Biases and Contextualize Results. PMID- 26838061 TI - Nonessential amino acid metabolism in breast cancer. AB - Interest in studying cancer metabolism has risen in recent years, as it has become evident that the relationship between cancer and metabolic pathways could reveal novel biomarkers and therapeutic targets. Metabolic starvation therapy is particularly promising due to its low toxicity. Nonessential amino acids are promising metabolites for such therapy because they become essential in many tumor cells, including breast cancer cells. This review will focus on four nonessential amino acid metabolism pathways: glutamine-glutamate, serine-glycine, cysteine, and arginine-proline metabolism. Recent studies of these amino acids have revealed metabolic enzymes that have the potential to be effective as cancer therapy targets or biomarkers for response to metabolic starvation therapy. The review will also discuss features of nonessential amino acid metabolism that merit further investigation to determine their relevancy to breast cancer treatment. PMID- 26838062 TI - [TAVI in Germany. What have we learned from current studies?]. AB - Transcatheter aortic valve implantation (TAVI) has become an established treatment for symptomatic aortic valve stenosis in inoperable patients and high risk patients. In Germany the TAVI procedure has now surpassed the annual numbers of isolated surgical aortic valve replacement with a recent trend towards treatment of intermediate-risk patients; however, before TAVI can also be used in patients with lower surgical risk, studies are required to demonstrate the safety and efficacy of this method for this patient population. PMID- 26838063 TI - A molecular mechanism realizing sequence-specific recognition of nucleic acids by TDP-43. AB - TAR DNA-binding protein 43 (TDP-43) is a DNA/RNA-binding protein containing two consecutive RNA recognition motifs (RRM1 and RRM2) in tandem. Functional abnormality of TDP-43 has been proposed to cause neurodegeneration, but it remains obscure how the physiological functions of this protein are regulated. Here, we show distinct roles of RRM1 and RRM2 in the sequence-specific substrate recognition of TDP-43. RRM1 was found to bind a wide spectrum of ssDNA sequences, while no binding was observed between RRM2 and ssDNA. When two RRMs are fused in tandem as in native TDP-43, the fused construct almost exclusively binds ssDNA with a TG-repeat sequence. In contrast, such sequence-specificity was not observed in a simple mixture of RRM1 and RRM2. We thus propose that the spatial arrangement of multiple RRMs in DNA/RNA binding proteins provides steric effects on the substrate-binding site and thereby controls the specificity of its substrate nucleotide sequences. PMID- 26838064 TI - EURADOS INTERCOMPARISONS ON WHOLE-BODY DOSEMETERS FOR PHOTONS FROM 2008 TO 2014. AB - Starting in 2008 the European Dosimetry Group (EURADOS) has been performing international intercomparisons on photon whole-body dosemeters for individual monitoring services. These intercomparisons were organised (on a biannual basis) in 2008, 2010, 2012 and 2014, each time with a similar set-up but with small alterations in the subsequent irradiation plans. With an increasing number of participants and participating systems, this intercomparison action has become an important tool for individual monitoring services to test their whole-body dosimetry systems, compare their results with other services or systems and to improve the quality of their dosimetry. The paper presents and compares the results of these four intercomparisons and compares the dosimetric results for the participating system types. Major dosimetric problems of the individual monitoring services are identified, and trends in the dosimetric performance of the different systems are shown. This gives the opportunity to identify some dosimetry issues that should be improved by application of the monitoring services' quality assurance systems and QA procedures. PMID- 26838065 TI - SECONDARY STANDARD CALIBRATION, MEASUREMENT AND IRRADIATION CAPABILITIES OF THE INDIVIDUAL MONITORING SERVICE AT THE HELMHOLTZ ZENTRUM MUNCHEN: ASPECTS OF UNCERTAINTY AND AUTOMATION. AB - The individual monitoring service at the Helmholtz Zentrum Munchen has adopted the recommendations of the ISO 4037 and 6980 standards series as base of its dosimetric systems for X-ray, gamma and beta dosimetry. These standards define technical requirements for radiation spectra and measurement processes, but leave flexibility in the implementation of irradiations as well as in the resulting uncertainty in dose or dose rate. This article provides an example for their practical implementation in the Munich IAEA/WHO secondary standard dosimetry laboratory. It focusses on two aspects: automation issues and uncertainties in calibration. PMID- 26838066 TI - COMPARISON OF MONOENERGETIC PHOTON ORGAN DOSE RATE COEFFICIENTS FOR STYLIZED AND VOXEL PHANTOMS SUBMERGED IN AIR. AB - As part of a broader effort to calculate effective dose rate coefficients for external exposure to photons and electrons emitted by radionuclides distributed in air, soil or water, age-specific stylized phantoms have been employed to determine dose coefficients relating dose rate to organs and tissues in the body. In this article, dose rate coefficients computed using the International Commission on Radiological Protection reference adult male voxel phantom are compared with values computed using the Oak Ridge National Laboratory adult male stylized phantom in an air submersion exposure geometry. Monte Carlo calculations for both phantoms were performed for monoenergetic source photons in the range of 30 keV to 5 MeV. These calculations largely result in differences under 10 % for photon energies above 50 keV, and it can be expected that both models show comparable results for the environmental sources of radionuclides. PMID- 26838067 TI - RADIATION PROTECTION IN AN INTERVENTIONAL LABORATORY: A COMPARATIVE STUDY OF AUSTRALIAN AND SAUDI ARABIAN HOSPITALS. AB - This study aimed to investigate whether the use of protection devices and attitudes of interventional professionals (including radiologists, cardiologists, vascular surgeons, medical imaging technicians and nurses) towards radiation protection will differ between Saudi Arabian and Australian hospitals. Hard copies of an anonymous survey were distributed to 10 and 6 clinical departments in the Eastern province of Saudi Arabia and metropolitan hospitals in Western Australia, respectively. The overall response rate was 43 % comprising 110 Australian participants and 63 % comprising 147 Saudi participants. Analysis showed that Australian respondents differed significantly from Saudi respondents with respect to their usages of leaded glasses (p < 0.001), ceiling-suspended lead screen (p < 0.001) and lead drape suspended from the table (p < 0.001). This study indicates that the trained interventional professionals in Australia tend to adhere to benefit from having an array of tools for personal radiation protection than the corresponding group in Saudi Arabia. PMID- 26838068 TI - Dynamic changes in global microRNAome and transcriptome reveal complex miRNA-mRNA regulated host response to Japanese Encephalitis Virus in microglial cells. AB - Microglia cells in the brain play essential role during Japanese Encephalitis Virus (JEV) infection and may lead to change in microRNA (miRNA) and mRNA profile. These changes may together control disease outcome. Using Affymetrix microarray platform, we profiled cellular miRNA and mRNA expression at multiple time points during viral infection in human microglial (CHME3) cells. In silico analysis of microarray data revealed a phased pattern of miRNAs expression, associated with JEV replication and provided unique signatures of infection. Target prediction and pathway enrichment analysis identified anti correlation between differentially expressed miRNA and the gene expression at multiple time point which ultimately affected diverse signaling pathways including Notch signaling pathways in microglia. Activation of Notch pathway during JEV infection was demonstrated in vitro and in vivo. The expression of a subset of miRNAs that target multiple genes in Notch signaling pathways were suppressed and their overexpression could affect JEV induced immune response. Further analysis provided evidence for the possible presence of cellular competing endogenous RNA (ceRNA) associated with innate immune response. Collectively, our data provide a uniquely comprehensive view of the changes in the host miRNAs induced by JEV during cellular infection and identify Notch pathway in modulating microglia mediated inflammation. PMID- 26838069 TI - Ophiopogonin D maintains Ca2+ homeostasis in rat cardiomyocytes in vitro by upregulating CYP2J3/EETs and suppressing ER stress. AB - AIM: CYP2J3 in myocardium metabolizes arachidonic acid to 4 regioisomeric epoxyeicosatrienoic acids (EETs), which have diverse biological activities in rat heart. In this study we examined whether CYP2J3 was involved in cardioprotective effects of ophiopogonin D (OPD), a steroidal glycoside isolated from Chinese herb Radix ophiopogonis. METHODS: Rat cardiomyoblast cell line (H9c2 cells) was tested. Intracellular Ca(2+) concentrations ([Ca(2+)]i) were measured using Fluo 4/AM. The expression of calcium-regulating molecules and ER stress signaling molecules was measured with qRT-PCR and Western blot analyses. Cell apoptosis was quantified with Hoechst 33258 staining and TUNEL assay. The level of 14,15-DHET, a stable metabolite of 14,15-EET, was assessed with ELISA. RESULTS: Angiotensin II (10(-6) mol/L) significantly decreased the expression of calcium-regulating molecules (SERCA2a, PLB, RyR2 and FKBP12.6), and elevated [Ca(2+)]i in H9c2 cells. Furthermore, angiotensin II markedly increased the expression of ER stress signaling molecules (GRP78, CHOP, p-JNK and cleaved caspase-12) and ER stress mediated apoptosis. OPD (100, 250 and 500 nmol/L) dose-dependently increased CYP2J3 expression and 14,15-DHET levels in normal H9c2 cells. Pretreatment of H9c2 cells with OPD suppressed angiotensin II-induced abnormalities in Ca(2+) homeostasis, ER stress responses and apoptosis. Overexpression of CYP2J3 or addition of exogenous 14,15-EET also prevented angiotensin II-induced abnormalities in Ca(2+) homeostasis, whereas transfection with CYP2J3 siRNA diminished the effects of OPD on Ca(2+) homeostasis. Furthermore, the intracellular Ca(2+) chelator BAPTA suppressed angiotensin II-induced ER stress responses and apoptosis in H9c2 cells. CONCLUSION: OPD is a novel CYP2J3 inducer that may offer a therapeutic benefit in treatment of cardiovascular diseases related to disturbance of Ca(2+) homeostasis and ER stress. PMID- 26838070 TI - A novel synthetic compound MCAP suppresses LPS-induced murine microglial activation in vitro via inhibiting NF-kB and p38 MAPK pathways. AB - AIM: To investigate the anti-neuroinflammatory activity of a novel synthetic compound, 7-methylchroman-2-carboxylic acid N-(2-trifluoromethyl) phenylamide (MCAP) against LPS-induced microglial activation in vitro. METHODS: Primary mouse microglia and BV2 microglia cells were exposed to LPS (50 or 100 ng/mL). The expression of iNOS and COX-2, proinflammatory cytokines, NF-kappaB and p38 MAPK signaling molecules were analyzed by RT-PCR, Western blot and ELISA. The morphological changes of microglia and nuclear translocation of NF-KB were visualized using phase contrast and fluorescence microscopy, respectively. RESULTS: Pretreatment with MCAP (0.1, 1, 10 MUmol/L) dose-dependently inhibited LPS-induced expression of iNOS and COX-2 in BV2 microglia cells. Similar results were obtained in primary microglia pretreated with MCAP (0.1, 0.5 MUmol/L). MCAP dose-dependently abated LPS-induced release of TNF-alpha, IL-6 and IL-1beta, and mitigated LPS-induced activation of NF-kappaB by reducing the phosphorylation of IkappaBalpha in BV2 microglia cells. Moreover, MCAP attenuated LPS-induced phosphorylation of p38 MAPK, whereas SB203580, a p38 MAPK inhibitor, significantly potentiated MCAP-caused inhibition on the expression of MEF-2 (a transcription factor downstream of p38 MAPK). CONCLUSION: MCAP exerts anti inflammatory effects in murine microglia in vitro by inhibiting the p38 MAPK and NF-kappaB signaling pathways and proinflammatory responses. MCAP may be developed as a novel agent for treating diseases involving activated microglial cells. PMID- 26838071 TI - Curcumin attenuates high glucose-induced podocyte apoptosis by regulating functional connections between caveolin-1 phosphorylation and ROS. AB - AIM: Caveolin-1 (cav-1) is a major multifunctional scaffolding protein of caveolae. Cav-1 is primarily expressed in mesangial cells, renal proximal tubule cells and podocytes in kidneys. Recent evidence shows that the functional connections between cav-1 and ROS play a key role in many diseases. In this study we investigated whether regulating the functional connections between cav-1 and ROS in kidneys contributed to the beneficial effects of curcumin in treating diabetic nephropathy in vitro and in vivo. METHODS: Cultured mouse podocytes (mpc5) were incubated in a high glucose (HG, 30 mmol/L) medium for 24, 48 or 72 h. Male rats were injected with STZ (60 mg/kg, ip) to induce diabetes. ROS generation, SOD activity, MDA content and caspase-3 activity in the cultured cells and kidney cortex homogenate were determined. Apoptotic proteins and cav-1 phosphorylation were analyzed using Western blot analyses. RESULTS: Incubation in HG-containing medium time-dependently increased ROS production, oxidative stress, apoptosis, and cav-1 phosphorylation in podocytes. Pretreatment with curcumin (1, 5, and 10 MUmol/L) dose-dependently attenuated these abnormalities in HG-treated podocytes. Furthermore, in HG-containing medium, the podocytes transfected with a recombinant plasmid GFP-cav-1 Y14F (mutation at a cav-1 phosphorylation site) exhibited significantly decreased ROS production and apoptosis compared with the cells transfected with empty vector. In diabetic rats, administration of curcumin (100 or 200 mg/kg body weight per day, ig, for 8 weeks) not only significantly improved the renal function, but also suppressed ROS levels, oxidative stress, apoptosis and cav-1 phosphorylation in the kidneys. CONCLUSION: Curcumin attenuates high glucose-induced podocyte apoptosis in vitro and diabetic nephropathy in vivo partly through regulating the functional connections between cav-1 phosphorylation and ROS. PMID- 26838073 TI - A new coumarin derivative, IMM-H004, attenuates okadaic acid-induced spatial memory impairment in rats. AB - AIM: A novel coumarin derivative 7-hydroxy-5-methoxy-4-methyl-3-(4 methylpiperazin-1-yl)-coumarin (IMM-H004) has shown anti-apoptotic, anti inflammatory and neuroprotective activities. In this study we investigated the effects of IMM-H004 on spatial memory in rats treated with okadaic acid (OKA), which was used to imitate Alzheimer's disease (AD)-like symptoms. METHODS: SD rats were administered IMM-H004 (8 mg.kg(-1).d(-1), ig) or donepezil (positive control, 1 mg.kg(-1).d(-1), ig) for 25 d. On d 8 and 9, OKA (200 ng) was microinjected into the right ventricle. Morris water maze test was used to evaluate the spatial memory impairments. Tau and beta-amyloid (Abeta) pathology in the hippocampus was detected using Western blot and immunohistochemistry. TUNEL staining was used to detect cell apoptosis. RESULTS: OKA-treated rats showed significant impairments of spatial memory in Morris water maze test, which were largely reversed by administration of IMM-H004 or donepezil. Furthermore, OKA-treated rats exhibited significantly increased phosphorylation of tau, deposits of Abeta protein and cell apoptosis in the hippocampus, which were also reversed by administration of IMM-H004 or donepezil. CONCLUSION: Administration of IMM-H004 or donepezil protects rats against OKA-induced spatial memory impairments via attenuating tau or Abeta pathology. Thus, IMM-H004 may be developed as a therapeutic agent for the treatment of AD. PMID- 26838072 TI - Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases. AB - Endoplasmic reticulum is a principal organelle responsible for folding, post translational modifications and transport of secretory, luminal and membrane proteins, thus palys an important rale in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) is a condition that is accelerated by accumulation of unfolded/misfolded proteins after endoplasmic reticulum environment disturbance, triggered by a variety of physiological and pathological factors, such as nutrient deprivation, altered glycosylation, calcium depletion, oxidative stress, DNA damage and energy disturbance, etc. ERS may initiate the unfolded protein response (UPR) to restore cellular homeostasis or lead to apoptosis. Numerous studies have clarified the link between ERS and cardiovascular diseases. This review focuses on ERS-associated molecular mechanisms that participate in physiological and pathophysiological processes of heart and blood vessels. In addition, a number of drugs that regulate ERS was introduced, which may be used to treat cardiovascular diseases. This review may open new avenues for studying the pathogenesis of cardiovascular diseases and discovering novel drugs targeting ERS. PMID- 26838075 TI - Chronic administration of caderofloxacin, a new fluoroquinolone, increases hepatic CYP2E1 expression and activity in rats. AB - AIM: Caderofloxacin is a new fluoroquinolone that is under phase III clinical trials in China. Here we examined the effects of caderofloxacin on rat hepatic cytochrome P450 (CYP450) isoforms as well as the potential of caderofloxacin interacting with co-administered drugs. METHODS: Male rats were treated with caderofloxacin (9 mg/kg, ig) once or twice daily for 14 consecutive days. The effects of caderofloxacin on CYP3A, 2D6, 2C19, 1A2, 2E1 and 2C9 were evaluated using a "cocktail" of 6 probes (midazolam, dextromethorphan, omeprazole, theophylline, chlorzoxazone and diclofenac) injected on d 0 (prior to caderofloxacin exposure) and d 15 (after caderofloxacin exposure). Hepatic microsomes from the caderofloxacin-treated rats were used to assess CYP2E1 activity and chlorzoxazone metabolism. The expression of CYP2E1 mRNA and protein in hepatic microsomes was analyzed with RT-PCR and Western blotting, respectively. RESULTS: Fourteen-day administration of caderofloxacin significantly increased the activity of hepatic CYP2E1, leading to enhanced metabolism of chlorzoxazone. In vitro microsomal study confirmed that CYP2E1 was a major metabolic enzyme involved in chlorzoxazone metabolism, and the 14-d administration of caderofloxacin significantly increased the activity of CYP2E1 in hepatic microsomes, resulting in increased formation of 6 hydroxychlorzoxazone. Furthermore, the 14-d administration of caderofloxacin significantly increased the expression of CYP2E1 mRNA and protein in liver microsomes, which was consistent with the pharmacokinetic results. CONCLUSION: Fourteen-day administration of caderofloxacin can induce the expression and activity of hepatic CYP2E1 in rats. When caderofloxacin is administered, a potential drug-drug interaction mediated by CYP2E1 induction should be considered. PMID- 26838076 TI - Hypoglycemia: Adverse Cardiovascular Outcomes in Non-Critically Ill People with Type 2 Diabetes. AB - BACKGROUND: Hypoglycemia is associated with adverse health outcomes and can result in vascular events in diabetic patients. The impact of hypoglycemia on cardiovascular outcomes in non-critically ill people with diabetes is not well determined. So, we examined short-term cardiovascular outcomes of hypoglycemic events in people with type 2 diabetes treated with insulin during routine clinical care. METHODS: This study was conducted in Tehran, Iran from January 2012 to January 2013. One hundred and twenty non-critically ill people with type 2 diabetes on oral glucose lowering drugs were enrolled. Insulin therapy was initiated for uncontrolled diabetes. The patients were educated to perform self monitoring of blood glucose on a daily basis. Furthermore, they were asked to record the results if they experienced any symptom indicative of hypoglycemia during the 24 weeks of the study. The occurrence of any major cardiovascular event including unstable angina, fatal or non-fatal myocardial infarction, fatal and non-fatal stroke, or death from cardiovascular cause was also evaluated based on the patients' hospital records. RESULTS: There were 210 hypoglycemic episodes and 31 major cardiovascular events. Forty four percent of patients with documented hypoglycemic episodes developed cardiovascular events compared to 15.6% of those who did not experience any hypoglycemia (P = 0.001). The odds ratio for occurrence of major cardiovascular events related to hypoglycemia was 7.41 (CI = 2.15-25.47) with a risk ratio of 2.66. CONCLUSION: Hypoglycemia is a major risk factor for occurrence of the first major cardiovascular event in non critically ill people with type 2 diabetes initiating insulin therapy. PMID- 26838074 TI - Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats. AB - AIM: Monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. This study was designed to characterize the pharmacokinetics and disposition of monoterpene glycosides. METHODS: Systemic exposure to Chishao monoterpene glycosides was assessed in human subjects receiving an intravenous infusion and multiple infusions of XueBiJing injection, followed by assessment of the pharmacokinetics of the major circulating compounds. Supportive rat studies were also performed. Membrane permeability and plasma-protein binding were assessed in vitro. RESULTS: A total of 18 monoterpene glycosides were detected in XueBiJing injection (content levels, 0.001-2.47 mmol/L), and paeoniflorin accounted for 85.5% of the total dose of monoterpene glycosides detected. In human subjects, unchanged paeoniflorin exhibited considerable levels of systemic exposure with elimination half-lives of 1.2-1.3 h; no significant metabolite was detected. Oxypaeoniflorin and albiflorin exhibited low exposure levels, and the remaining minor monoterpene glycosides were negligible or undetected. Glomerular filtration-based renal excretion was the major elimination pathway of paeoniflorin, which was poorly bound to plasma protein. In rats, the systemic exposure level of paeoniflorin increased proportionally as the dose was increased. Rat lung, heart, and liver exposure levels of paeoniflorin were lower than the plasma level, with the exception of the kidney level, which was 4.3-fold greater than the plasma level; brain penetration was limited by the poor membrane permeability. CONCLUSION: Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance. PMID- 26838077 TI - Mutation in TWINKLE in a Large Iranian Family with Progressive External Ophthalmoplegia, Myopathy, Dysphagia and Dysphonia, and Behavior Change. AB - BACKGROUND: TWINKLE (c10orf2) gene is responsible for autosomal dominant progressive external ophthalmoplegia (PEO). In rare cases, additional features such as muscle weakness, peripheral neuropathy, ataxia, cardiomyopathy, dysphagia, dysphonia, cataracts, depression, dementia, parkinsonism, and hearing loss have been reported in association with heterozygous mutations of the TWINKLE gene. METHODS: We have studied a large Iranian family with myopathy, dysphonia, dysphagia, and behavior change in addition to PEO in affected members. RESULTS: We identified a missense mutation c.1121G > A in the c10orf2 gene in all affected members. Early death is a novel feature seen in affected members of this family that has not been reported to date. CONCLUSION: The association of PEO, myopathy, dysphonia, dysphagia, behavior change and early death has not been previously reported in the literature or other patients with this mutation. PMID- 26838078 TI - The Effects of Inulin on Characteristics of Lactobacillus paracasei TD3 (IBRC-M 10784) as Probiotic Bacteria in vitro. AB - INTRODUCTION: Probiotics, as live microbial food ingredients or functional foods, are often related to health promotion and diseases prevention. The growth of these beneficial probiotics was improved by non-digestible food ingredients that are defined as prebiotics. Inulin is one of the known prebiotics that improves the gastrointestinal health. AIM: The aim of this study was to evaluate the functional properties of Lactobacillus paracasei TD3 (IBRC-M 10784) and the effects of inulin as prebiotic on these properties in vitro. METHODS: The tolerance of L. paracasei TD3 for low pH and pepsin (stomach condition), bile salt and trypsin conditions (small intestine conditions), antibiotics and pathogenic bacteria were evaluated by different methods. RESULTS: Lactobacillus paracasei TD3 was obtained from TakGene Company. L. paracasei TD3 was resistant to acidic pH higher than 3.5 and was tolerant to pepsin condition lower than 0.723 ug/mL and to bile salts <= 0.4% w/v and tripsin condition equal to 72.32 u/g and lower. This strain was resistant to vancomycin, nalidixic acid, colistin and gentamicin while was sensitive to penicillin, streptomycin and tetracycline. L. paracasei TD3 showed antimicrobial activity against S. typhimurium, Sh. dysanteriae, Sh. flexneri and E. coli, respectively. Inulin promoted the growth of L. paracasei TD3 (log CFU) in different conditions and increased the antibacterial activity of L. paracasei TD3 against pathogenic bacteria without changing the tolerance of bacteria to pH and other conditions (P > 0.05). CONCLUSION: L. paracasei TD3 (IBRC-M 10784) in combination with inulin can be considered as valuable strain for further investigations in human clinical studies. PMID- 26838079 TI - Correlation between Heart, Liver and Pancreas Hemosiderosis Measured by MRI T2* among Thalassemia Major Patients from Iran. AB - INTRODUCTION: Major thalassemia patients need lifelong transfusions. The consequence of these repeated transfusions is iron accumulation in different organs. The main aim of the present study was to investigate the correlation between heart, liver and pancreas hemosiderosis in thalassemic patients from Iran. METHODS: This cross-sectional study was conducted on 164 major thalassemia patients at Zafar Adult Thalassemia Center, a referral thalassemia center in Tehran, Iran, from May to November 2014. All patients were on regular blood transfusion at 2-4 week intervals to keep their hemoglobin at a level of 7-9 gr/dL before each transfusion. Demographic data were gathered from patients' history. MRI T2* of liver, heart and pancreas were performed for all patients. RESULTS: There were a moderate correlation between pancreatic T2* and cardiac T2* relaxation times (r = 0.42, P < 0.001), a moderate correlation between T2* of pancreas and liver (r = 0.41, P < 0.001), and a weak correlation between T2* relaxation times of heart and liver (r = 0.31, P < 0.001). CONCLUSION: Poor correlation between liver and heart, as well as a weak to moderate correlation between pancreas and liver T2* relaxation times indicate that relying on liver MRI T2* to predict the exact condition of pancreas or heart iron overload might not be a reliable approach in thalassemia major patients. Our findings suggest the advantage of using pancreas and heart MRI T2* as a non-invasive method for estimation of iron overload instead of relying on liver MRI T2*. PMID- 26838080 TI - Protein Clustering and Interactome Analysis in Parkinson and Alzheimer's Diseases. AB - BACKGROUND: Alzheimer and Parkinson diseases (AD and PD) are the two most important neurodegenerative disorders. This paper aims to determine the possible molecular linkage between these two common neurodegenerative diseases by a combination of computational investigations. METHODS: According to our aim, common sets of identified proteins from the KEGG database were further analyzed based on Gene Ontology (GO) annotation and sequence similarities by the agglomerative hierarchical clustering. Proteins possessing same characteristics were categorized based on biological features in distinct clusters using the R programming software. In addition to this, by the use of DAVID Program and PPI network analysis, more insight can be achieved. RESULTS: The results of this study indicated that 23 proteins are common between these two diseases. Their ontology evaluations by application of clustering methods showed that proteins belonging to a specific cluster indicate discrete properties that are different from other clusters. Furthermore, PPI network analysis confirms that the proteins with similarity ontology and sequence are also in close relationship. CONCLUSION: In conclusion, assessment of protein features supported the idea that mitochondria are the main malfunction compartment in AD and PD. Some of these common properties are apoptosis and mitochondria oxidation pathways that can be used for drug targeting. Moreover, examination of other neurodegenerative diseases can be helpful for comprehensive understanding of the origin of these diseases. PMID- 26838081 TI - The Best Obesity Indices to Use in a Single Factor Model Indicating Metabolic Syndrome: a Population Based Study. AB - OBJECTIVE: Although metabolic syndrome (MetS) is a major health problem worldwide, there is no universal agreement on its definition. One of the major disagreements is dealing with the issue of obesity in this definition. This study was conducted to determine a preferably better index of obesity which can be interrelated with other components of MetS in a single factor model of MetS. DESIGN: Out of 6140 participants of a cohort study of subjects aged 10-90 years in northern Iran, the baseline data of 5616 participants aged 18-75 was considered. Confirmatory factor analysis was conducted using AMOS software to evaluate a single factor model of MetS in which blood pressure, triglyceride (TG), high density lipoprotein (HDL), fasting blood sugar (FBS) and obesity measures including waist circumference (WC), body mass index (BMI), waist to hip ratio (WHR) and waist to height ratio (WHtR) were used as indicators of metabolic syndrome. Four single factor models differing from each other by obesity indices were evaluated. The models were evaluated in all 5616 subjects and 4931 subjects without diabetes mellitus according to sex separately. RESULTS: All single factor models had appropriate fit indices with CFI > 0.95, GFI > 0.95 and RMSEA < 0.08 in non-diabetic population, wherein all models obtained the best values of fit indices in men and good fit indices in women. In the general population of men, the single factor models built based on WHR (Chi-square=6.9, df=2, P-value=0.031, RMSEA = 0.028, CI = 0.007-0.052, CFI = 0.994, GFI = 0.999 and AIC = 22.9) and WHtR (Chi-square = 9.97, df = 2, P-value = 0.007, RMSEA = 0.036, CI = 0.016 0.059, CFI = 0.992, GFI = 0.998 and AIC = 25.97) were fitted properly with data while in th general population of women, the model based on WHR obtained better fit indices (Chi-square = 7.5, df = 2, P-value = 0.023, RMSEA = 0.033, CI = 0.011 0.060, CFI = 0.994, GFI = 0.998 and AIC = 23.5). Models based on WHtR obtained better regression weights than WHR. CONCLUSION: While single factor validity of MetS was confirmed in almost all models, the best models were different according to sex and population of study. PMID- 26838082 TI - Wealth-related Inequality in Utilization of Antihypertensive Medicines in Iran: an Ecological Study on Population Level Data. AB - BACKGROUND: We aim to evaluate the trend of national and sub-national (provincial) utilization pattern of antihypertensive medicines in the Iranian population in the past decade and evaluate whether there is any wealth-related inequality in utilization of these medicines among different provinces. METHOD: Either fixed effect or random effect linear panel data model was used to check the effect of wealth index on utilization of all antihypertensive medicines and each class, adjusting for other covariates including years of schooling, urbanization, mean age, and food type of provinces. The principal component analysis was applied to make summery measures for covariates using available national datasets. RESULTS: The effect of wealth category on the utilization of all antihypertensive medicines among Iranian provinces was positive and significant (0.84; 95% CI: 0.09, 1.59). Accordingly as subgroup analysis, in BBs and CCBs classes, the effects of wealth category on utilization of medicines were positive and significant (0.36; 95% CI: 0.12, 0.60 and 0.27; 95% CI: 0.07, 0.40, respectively). However in ACEIs and Diuretics classes, the effects of wealth category were positive but not significant. In ARBs class, the effect of wealth on utilization was negative and not significant (-0.04; 95% CI: -0.27, 0.18). CONCLUSION: According to this study, an inequality could be observed in Iran related to wealth category in utilization of total antihypertensive medicines between provinces. PMID- 26838084 TI - Repeated Intraportal Injection of Mesenchymal Stem Cells in Combination with Pioglitazone in Patients with Compensated Cirrhosis: A Clinical Report of Two Cases. AB - BACKGROUND: Transplantation of mesenchymal stem cells (MSCs) in combination with pioglitazone, an agonist of peroxisome proliferator-activated receptor-gamma (PPAR-gamma), can reduce liver fibrosis in models of liver injury. In this study, we conducted a pilot study of intraportal infusion of autologous MSCs in combination with pioglitazone to assess safety, feasibility, and effectiveness in patients with compensated cirrhosis. METHODS: Two patients with compensated cirrhosis were enrolled in this study. Intraportal autologous bone marrow-derived MSCs were transplanted twice (6 months interval) to the patients. Meanwhile, 30 mg/day pioglitazone was prescribed for 12 months. Patients were assessed at baseline and months 1, 3, 6, and 12 post-infusion. RESULTS: Procedural complications or any major adverse effects did not occur in this pilot study. The patients' clinical conditions remained stable with no evidence of deterioration during the course of the study. A transient improvement in the Model for End-Stage Liver Disease (MELD) score was observed at month 3 post infusion in one patient, which eventually returned to baseline at month 12. CONCLUSION: The combination of pioglitazone with MSCs is safe and feasible. The data justify further study of the combination therapy in cirrhotic patients. PMID- 26838083 TI - Relationship between Tooth Loss, Functional Dyspepsia and Gastro-Esophageal Reflux Disorder among Isfahani Adults. AB - BACKGROUND: Few studies have assessed the relationship between tooth loss and upper gastro-intestinal (GI) disorders including functional dyspepsia (FD) and gastro-esophageal reflux disease (GERD). This study aimed to investigate the relation between dental status and FD, its components and GERD among a large group of Isfahani adults. METHODS: In a cross-sectional study from April to May 2010, the dental status of 4109 Isfahani adults was evaluated using a self administered questionnaire. Participants were categorized into three main groups: those with full dentition, individual who had lost 1-5 teeth and those who had lost >5 teeth. FD, its components and GERD were defined using Rome III criteria. Multivariable logistic regression was used to examine the relationship between dental status and gastrointestinal disorders. RESULTS: After adjustment for potential confounders, we found no significant association between dental status, FD and GERD. However, individuals who had lost 1-5 teeth and >5 teeth had 34% and 109% greater odds for early satiation, respectively. In addition, individuals who had lost 1-5 teeth were 24% likely to have postprandial fullness and epigastric pain. Stratified analyses by gender also revealed a significant association between dental status and GERD as well as FD in females; such that those who had lost 1-5 teeth had 33% greater chance for GERD and those who had lost >5 teeth were 101% more likely to have FD compared with those with full dentition. CONCLUSION: We found significant positive associations between tooth loss, GERD and FD in women, but not in men. We also found significant relations between tooth loss and components of FD, especially early satiety in the entire population. PMID- 26838085 TI - Increased Serum Pepsinogen II Level as a Marker of Pangastritis and Corpus Predominant Gastritis in Gastric Cancer Prevention. AB - Serum pepsinogen I and II are considered as indicators of changes in gastric morphology. Important publications from the last decades are reviewed with regard to the serum level of these biomarkers for the diagnosis of normal gastric mucosa, diffuse gastritis and its change to atrophic gastritis and intestinal metaplasia as well as gastric cancer. Due to the low sensitivity of serum biomarkers for diagnosis of gastric cancer, especially at its early stage and the poor prognosis of the tumor at the time of diagnosis, its prevention by eradication of H. pylori remains the mandatory strategy. On the other hand, the severity of regression and non-reversibility of precancerous lesions and intestinal metaplasia in gastric mucosa through eradication of H. pylori make it necessary to diagnose diffuse gastritis at its early stage. Increased serum pepsinogen II compared to normal serum pepsinogen I seems to indicate the presence of diffuse gastritis without precancerous lesions suitable for eradication of H. pylori infection, when it is serologically positive. A diagram illustrates the strategy of this therapeutic measure depending on the age of people and the level of serum biomarkers in areas with high gastric cancer prevalence. PMID- 26838086 TI - Hormone Therapy for Relieving Postmenopausal Vasomotor Symptoms: A Systematic Review. AB - BACKGROUND: Menopause is a critical phenomenon in women's life. After cardiac diseases, menopause is the second major cause of living with a disability in 45 60 year old women. The majority of women will experience bothersome vasomotor symptoms (VMS). Menopausal hormone therapy (MHT) is the most effective treatment for these symptoms. The objective of this review is to focus on hormone therapy for relieving postmenopausal vasomotor symptoms. METHODS: For this systematic review, we primarily explored 125 papers published about hormone therapy for VMS from 2001 to 2015 by searching with combinations of the keywords in various databases. Among those, 59 papers met the initial search criteria and among them, 9 papers were potentially retrievable and reviewed. All included studies used estrogen formulations in the management of VMS. RESULTS: Nine studies met all inclusion criteria. All studies assessed the effects of hormone replacement therapy on VSM. The results showed that low-dose oral and transdermal estrogen in all dose ranges were more likely than placebo to decrease the frequency of VMS. Indeed, the nanostructured formulation was safe and effective in relieving the symptoms of menopause. The mean daily decrease in the number of hot flashes from baseline was found in the studies. CONCLUSION: MHT has a complex pattern. Understanding the natural history of VMS, and the risks and benefits of both hormonal therapies, helps to individualize management plans. Low-dose estrogen based therapies can be the most effective regimens to relieve VMS. These medications can be used by different administration routes and formulations. PMID- 26838087 TI - Management of Intravenous Leiomyomatosis of Uterus with Extension to Heart. AB - Leiomyoma is a benign smooth muscle tumor. Intra-venous extensions of these tumors occur due to tumor growth within uterine vein or lymphatic vessels. In rare cases, intracaval and intracardiac extension can also be seen. Clinical suspicion of this disease should become certain by use of imaging techniques. While the treatment is complete resection of the tumor, one or two-stage surgery can be planned for patient depending on tumor extension and patient's condition. In this report, a 52-year-old woman with a rare presentation of uterine leiomyoma will be discussed. While the tumor was extended toward right atrium, the patient had nonspecific symptoms. By use of two-stage surgery, separated laparotomy and cardiopulmonary bypass, the tumor was completely removed. PMID- 26838088 TI - Intranuclear Pseudo-inclusions and Grooves in Fine Needle Aspiration Cytology of Pulmonary Carcinoid Tumor. AB - Cytologic findings of pulmonary carcinoid have been well described. We report new cytological findings in a case of carcinoid tumor. The patient is a 36-year-old man presenting with hemoptysis of about six months in duration. Chest CT scans showed a well-defined round polypoid lesion measuring 1 * 1 cm within the right upper lobe of the bronchus with hyperinflation of the right upper lobe. Trans bronchial fine needle aspiration and biopsy were done. Cytologic smears showed isolated and loose clusters of uniform round to spindle shape cells with round centrally located nuclei, fine granular (salt and pepper) chromatin and pale cytoplasm. Intranuclear pseudo-inclusions and grooves were seen in some tumor cells. No mitotic figures or necrosis were evident. A cytological diagnosis of carcinoid tumor was made and histopathologic examination and subsequent immunohistochemical study confirmed the diagnosis. Carcinoid tumor may be reliably diagnosed on fine needle aspiration cytology smears. Intranuclear pseudo inclusions and grooves may be evident in tumor cells. PMID- 26838090 TI - Dr. Amir Masoud Emadi. PMID- 26838089 TI - A History of Leishmaniasis in Iran from 19th Century Onward. AB - The history of leishmaniasis dates back to the distant past; however, its etiologic agent was unidentified until the mid-19th century. Here is an overview of some historical aspects of leishmaniasis in Iran mainly focused on the cutaneous form, from the mid-19th century onwards. In addition, short biographies of several contemporary researchers and experts of leishmaniasis and their achievements in the past decades are presented. PMID- 26838091 TI - The Effects of Transdiagnostic Group CBT for Anxiety on Insomnia Symptoms. AB - Insomnia is a common feature among individuals with anxiety disorders. Studies of cognitive behavioral therapy (CBT) for anxiety report moderate effects on concomitant insomnia symptoms, but further research is still needed especially toward understanding how CBT for anxiety renders beneficial effects on insomnia. The current study examined changes in insomnia symptoms reported by 51 Veterans who participated in a group-based transdiagnostic CBT for anxiety intervention. In addition, insomnia symptoms were examined in relation to symptoms of general distress (GD), anhedonic depression (AD), and anxious arousal (AA) pre- to post treatment. Results revealed a small, though statistically significant (p < .05) beneficial effect on insomnia symptoms. When changes in GD, AD, and AA were simultaneously examined in relation to changes in insomnia, change in AA was the only significant predictor of insomnia symptoms. The current study highlights the role of AA in the relationship between anxiety disorders and insomnia and demonstrates that reductions in insomnia during transdiagnostic CBT for anxiety can be largely attributed to changes in AA. PMID- 26838092 TI - Polymerization of modified diaspirin cross-linked hemoglobin (DCLHb) with 1,6 bismaleimic-hexane. AB - Increasing the size of hemoglobin (Hb) by polymerization offers the benefits of reduced renal clearance and increased duration in the vascular circulation. With this goal, diaspirin cross-linked hemoglobin (DCLHb) was modified in order to keep one thiol group on the surface and then polymerized with 1,6-bismaleimic hexane (1,6-BMH) to increase the molecular weight. The HPLC results indicated that approximate 20% dimers to tetramers of DCLHb desired were achieved after the polymerization. It was also demonstrated that the oxygen-carrying capacity of the products was similar to natural heme. The present study is expected to improve the efficacy of the DCLHb as an oxygen therapeutic agent. PMID- 26838093 TI - Examining geographic and socio-economic differences in outpatient and inpatient consumer expenditures for treating HIV/AIDS in Nigeria. AB - INTRODUCTION: The expenditures on treatment of HIV/AIDS to households were examined to quantify the magnitude of the economic burden of HIV/AIDS to different population groups in Nigeria. The information will also provide a basis for increased action towards a reduction of the economic burden on many households when accessing antiretroviral therapy (ART). METHODS: A household survey was administered in three states, Adamawa, Akwa Ibom and Anambra, from the South-East, North-East and South-South zones of Nigeria, respectively. A pretested interviewer-administered questionnaire was used to collect data from a minimum sample of 1200 people living with HIV/AIDS (PLHIV). Data were collected on the medical and non-medical expenditures that patients incurred to treat HIV/AIDS for their last treatment episode within three months of the interview date. The expenditures were for outpatient visits (OPV) and inpatient stays (IPS). The incidence of catastrophic health expenditure (CHE) on ART treatment services was computed for OPV and IPS. Data were disaggregated by socio-economic status (SES) and geographic location of the households. RESULTS: The average OPV expenditures incurred by patients per OPV for HIV/AIDS treatment was US$6.1 with variations across SES and urban-rural residence. More than 95% of the surveyed households spent money on transportation to a treatment facility and over 70% spent money on food for OPV. For medical expenditures, the urbanites paid more than rural dwellers. Many patients incurred CHE during outpatient and inpatient visits. Compared to urban dwellers, rural dwellers incurred more CHE for outpatient (p=0.02) and inpatient visits (p=0.002). CONCLUSIONS: Treatment expenditures were quite high, inequitable and catastrophic in some instances, hence further jeopardizing the welfare of the households and the PLHIV. Strategically locating fully functional treatment centres to make them more accessible to PLHIV will largely reduce expenditures for travel and the need for food during visits. Additionally, financial risk-protection mechanisms such as treatment vouchers, reimbursement and health insurance that will significantly reduce the expenditures borne by PLHIV and their households in seeking ART should be implemented. PMID- 26838094 TI - Stem Cell-Based Human Blood-Brain Barrier Models for Drug Discovery and Delivery. AB - The development of novel neuropharmaceuticals requires the evaluation of blood brain barrier (BBB) permeability and toxicity. Recent studies have highlighted differences in the BBB among different species, with the most important differences involving the expression of P-glycoprotein (P-gp), multidrug resistance-associated proteins, transporters, and claudins. In addition, functional studies have shown that brain pharmacokinetics of P-glycoprotein substrates are different in humans and rodents. Therefore, human BBB models may be an important platform for initial drug screening before in vivo studies. This strategy might help to reduce costs in drug development and failures in clinical studies. We review the differences in the BBB among species, recent advances in the generation of human BBB models, and their applications in drug discovery and delivery. PMID- 26838096 TI - Approaches to reduce the glycemic response of gluten-free products: in vivo and in vitro studies. AB - This article aims to discuss the current approaches used to reduce the postprandial glycemic response (GR) of starchy gluten-free products (GFP) and to provide some further prospects. The GR is evaluated through in vivo trials to determine the glycemic index (GI) and the glycemic load (GL) of foods or using the in vitro starch digestibility method to predict the GI. The reviewed studies demonstrated that a reduction in the GR of GFP can be achieved by replacing traditionally used refined flours and starches with nutrient-dense alternative raw materials due to an increase in dietary fiber, resistant starch and protein contents, which can alter the rate of starch digestion, reduce the GI and dilute the amount of available carbohydrate; both the factors contribute to reduce the GL. The addition of viscous dietary fibers could also be a successful way to reduce the GR of GFP. Some studies have demonstrated the potential of germination of GF grains and sourdough fermentation in decreasing the GR of GF bread. Further studies could evaluate alternative GF flours, soluble fibers, resistant starch, and other formulation factors that may affect the GR of different types of GFP. New studies should be performed to test and optimize processing methods by considering the reduction of GR of GFP. Another key aspect for further investigation is the confirmation of the promising results obtained through in vitro assays by in vivo GI evaluation. PMID- 26838095 TI - Extracellular matrix remodeling in equine sarcoid: an immunohistochemical and molecular study. AB - BACKGROUND: Equine sarcoids are locally invasive, fibroblastic benign skin tumors. Bovine papillomavirus type-1 (BPV-1) and/or Bovine papillomavirus type-2 (BPV-2) are believed to be the causative agent of sarcoids, although the mechanisms by which the virus induce the tumor are still poorly understood. We hypothesized that in genetically predisposed equines latent BPV infection may be reactivated by immunosoppression and/or mechanical injury leading to a form of pathologic wound which may transform into a sarcoid. In this study, we investigated in 25 equine sarcoids and in five normal skin samples the histological features and evaluated the immunohistochemical and molecular expression of type I and type III Collagen, vimentin (VIM), alfa Smooth Muscle Actin (alpha-SMA), Matrix Metalloproteinase (MMPs) -2, 9, 14 and tissue inhibitor of metalloproteinase 2 (TIMP-2). RESULTS: In 64% of investigated sarcoids, type I collagen staining was stronger than that of type III collagen. In 80% of sarcoids, SFs were strongly positive for vimentin and negative for alpha-SMA; the remaining sarcoid samples (20%) showed 70-80% of SFs labeled for vim and approximately 20-30% labeled for alpha-SMA. Moreover, all sarcoid specimen showed a variable staining pattern (weak to moderate) for MMP-9 and MMP-14, and a moderate to strong staining for MMP-2 and TIMP-2. Biochemical analysis confirmed immunohistochemical results and showed in sarcoids, for the first time, the cleaved form of MMP9, the 35 KDa active species for MMP-9. CONCLUSIONS: This study revealed that in equine sarcoids exhibit an altered turnover of the Extracellular Matrix (ECM) deposition and degradation, as result of an altered expression of MMPs and TIMPs. Therefore, these observations seem to confirm that the basic mechanism for growth of equine sarcoids could be a neoplastic transformation during wound healing. PMID- 26838098 TI - Pathologic Features of Adult Renal Cortical Tumors. AB - In the past few years, a much better understanding of the morphologic spectrum of renal cortical tumors has resulted in a clinically highly relevant contemporary classification system of these tumors. The current and still evolving era of targeted therapies in kidney cancer further highlights the importance of the appropriate pathologic classification. The recently gained knowledge about molecular-driven antigen expression almost certainly will have a major role to play in the characterization, development, and evaluation of targeted therapies in kidney cancer in the future. PMID- 26838099 TI - Pediatric Renal Neoplasms. AB - Renal tumors in childhood consist of a diverse group of tumors ranging from the most common Wilms' tumor, to the uncommon and often fatal rhabdoid tumor. Diagnosis is based on morphologic features and aided by ancillary techniques such as immunohistochemistry and cytogenetics. Molecular techniques have helped identify a group of pediatric renal cell carcinomas that have specific translocations, called translocation-associated carcinomas. Differential diagnosis of the various tumors is discussed. Pathogenesis and nephroblastomatosis, the precursor lesions of Wilms tumor, also are discussed briefly, as are the handling of these tumor specimens and prognostic factors. PMID- 26838097 TI - Colorectal cancer-derived microvesicles modulate differentiation of human monocytes to macrophages. AB - BACKGROUND: Tumour-derived microvesicles (TMVs) are important players in tumour progression, modulating biological activity of immune cells e.g. lymphocytes, monocytes and macrophages. This phenomenon is particularly interesting in the progression of colon cancer, as macrophages in this type of tumour are relevant for the recovery processes. In the present study, the role of colon cancer cell derived microvesicles in monocyte differentiation and activity profile (polarization) was investigated. METHODS: Monocyte-derived macrophages (MDM) were differentiated in vitro in the presence of TMVs obtained from colon cancer: Caco 2, SW620, LoVo or SW480 cell lines and analysed according to their morphology and biological functions, as defined by cytokine secretion, reactive oxygen intermediate (ROI) production and cytotoxic activity against respective colon cancer cells. RESULTS: Monocytes differentiated with TMVs exhibited morphological and phenotypical characteristics of macrophages. An early contact (beginning with the first day of the in vitro culture) of monocytes with TMVs resulted in increased IL-10 secretion and only slightly elevated TNF release. Early, or prolonged contact resulted in low ROI production and low cytotoxicity against tumour cells. On the other hand, late contact of MDM with TMVs, stimulated MDM to significant TNF and IL-12 secretion, ROI production and enhanced cytotoxicity against tumour cells in vitro. In addition, differences in MDM response to TMVs from different cell lines were observed (according to cytokine secretion, ROI production and cytotoxicity against tumour cells in vitro). Biological activity, STATs phosphorylation and microRNA profiling of MDMs indicated differences in their polarization/activation status which may suggest mixed polarization type M1/M2 with the predominance of proinflammatory cells after late contact with TMVs. CONCLUSIONS: Macrophage activity (polarization status) may be regulated by contact with not only tumour cells but also with TMVs. Their final polarization status depends on the contact time, and probably on the vesicle "cargo", as signified by the distinct impact of TMVs which enabled the switching of MDM maturation to regulatory macrophages. PMID- 26838100 TI - Benign and Malignant Neoplasms of the Testis and Paratesticular Tissue. AB - Benign and malignant tumors of the testes and paratesticular tissues present an interesting spectrum of diagnostic entities often encountered in routine surgical pathology practice. Germ cell tumors are the most common tumors of the testes and, despite a rising incidence, have excellent prognosis because of their radiosensitivity and/or effective chemotherapeutic agents. The proper classification of these tumors aids in the choice of appropriate treatment options. This article reviews benign and malignant neoplastic entities of the testes and paratesticular tissues and illustrates the classic pathologic characteristics. The differential diagnosis, along with ancillary studies, clinical significance, and presentation are discussed also. PMID- 26838101 TI - Benign Diseases and Neoplasms of the Penis. AB - This article provides comprehensive review of benign diseases and neoplastic conditions of the penis. It describes and provides representative images of clinical, key pathologic features and ancillary techniques to aid in differential diagnoses. It examines these diseases from the epidemiologic standpoint, looks at environmental and genetic factors, and outlines the new histologic entities for penile neoplasms with distinct outcomes and clinical behavior that have been proposed in recent years. PMID- 26838102 TI - Molecular Pathology of the Genitourinary Tract: Molecular Pathology of Kidney and Testes. AB - With the advent of newer molecular technologies, our knowledge of cellular mechanisms with tumors of the kidney and testis has grown exponentially. Molecular technologies have led to better understanding of interplay between the von Hippel-Lindau gene and angiogenic cytokines in renal cancer and isochromosome 12p in testicular neoplasms. The result has been development of antiangiogenic targeted therapy within recent years that has become the mainstay treatment for metastatic renal cell cancer. In the near future, classification and diagnosis of renal and testicular tumors through morphologic analysis will be supplemented by molecular information correlating to prognosis and targeted therapy. This article outlines tumor molecular pathology of the kidney and testis encompassing current genomic, epigenomic, and proteonomic findings. PMID- 26838103 TI - Foreword. PMID- 26838104 TI - Preface. PMID- 26838106 TI - Editorial. PMID- 26838107 TI - Native Cardiac Valve Pathology. AB - Anatomy of the native cardiac valves, reasons for surgical excision and examination, and a summary of the gross examination and documentation are presented. Aortic stenosis, aortic valve regurgitation, tricuspid and pulmonary valve pathology, mitral stenosis, and mitral insufficiency are each presented with an overview, focused anatomy, and discussion of pathologic diagnosis by gross examination and histology. PMID- 26838108 TI - Practical Approach to the Evaluation of Prosthetic Mechanical and Tissue Replacement Heart Valves. AB - Mechanical and bioprosthetic substitute heart valves have dramatically improved life expectancy and quality of life in patients with valvular heart disease. Complications of substitute heart valves are a relatively infrequent occurrence, often due to thrombosis, infection, or structural/mechanical failure. It is important to accurately identify and systematically evaluate prosthetic heart valves when encountered as surgical pathology specimens or in the autopsy setting. PMID- 26838110 TI - Diagnostic Biopsies of the Native Heart. AB - Endomyocardial biopsy in the nontransplant setting can be diagnostic for particular diseases. Such disorders include amyloidosis, myocarditis, sarcoidosis, iron overload, glycogen storage disorders, and lysosomal storage disorders. The diagnostic features of these disorders on endomyocardial biopsy will be discussed along with the impact of endomyocardial biopsy-based diagnoses on patient management and prognosis. PMID- 26838109 TI - Cardiac Transplant Biopsies. AB - The endomyocardial biopsy remains the gold standard for assessing the status of the transplanted heart. It is the most consistently reliable method for the diagnosis and grading of acute cellular and antibody-mediated rejection. Recognition of specimen artifacts and other biopsy findings such as ischemic injury, Quilty effect, infection, and post-transplant lymphoproliferative disorder is important for accurate biopsy interpretation and differentiation from rejection. The endomyocardial biopsy provides important diagnostic information essential for optimal management of cardiac transplant recipients. PMID- 26838111 TI - Pathology of the Aorta. AB - The aorta is a distinctive surgical pathology specimen removed most frequently for aneurysm or dissection. Genetic syndromes, inflammatory processes and acquired diseases of aging result in aortic pathology; these are presented in terms of pathology, differential diagnosis and classification schemes. The pathologic context of a variety of commonly encountered histopathologies is described. PMID- 26838112 TI - Surgical Pathology of Small- and Medium-Sized Vessels. AB - Surgical pathologists encounter blood vessels in virtually every specimen they receive, but pathologies intrinsic to the vessels themselves are distinctly less common. Nevertheless, there are a variety of specific diagnoses and procedures involving vascular specimens that merit the attention of the anatomic pathologist. Etiologically, such pathologies can be broadly grouped into traumatic, degenerative, congenital, inflammatory, infectious, and neoplastic lesions. Major examples of most of these are discussed, including anuerysms, vasculitis, thrombosis/embolism, and atherosclerosis. PMID- 26838113 TI - Cardiac Tumors. AB - Cardiac neoplasms and other mass-forming lesions are not commonly encountered in surgical pathology practice. Fortunately, for the most part, these fall into a small group of well characterized and readily-recognized entities, although they are not without diagnostic dilemmas. A brief and practical synopsis of cardiac tumors is presented in this section with attention to more frequently encountered and clinically significant diagnostic challenges as well as pertinent clinical associations and prognostic information. PMID- 26838114 TI - Examination of the Cardiac Explant. AB - Examination of cardiac explants is a challenge to the surgical pathologist. This is due to the complex anatomy of the heart, the numerous pathologies unique to the heart, and the complexities of cardiovascular interventions including the transplant procedure itself. The dissection technique described permits complete evaluation of the heart with good photographic and histologic documentation while maintaining the integrity of the specimen. PMID- 26838115 TI - Pathologic Evaluation of Cardiovascular Medical Devices. AB - Cardiovascular devices such as coronary artery stents, ventricular assist devices, pacemakers, automated implantable cardioverter-defibrillators and septal closure devices are life saving and improve quality of life for millions of patients each year. Complications of these devices include thrombosis/thromboembolism, infection, structural failure and adverse material tissue interactions. These findings should be sought when these devices are encountered on the surgical pathology bench or at autopsy. PMID- 26838116 TI - Cardiovascular Pathology: A Subspecialty of Surgical Pathology. PMID- 26838118 TI - Concurrent Risperidone Administration Attenuates the Development of Locomotor Sensitization Following Sub-Chronic Phencyclidine in Rats. AB - INTRODUCTION: In schizophrenia early treatment may prevent disorder onset, or at least minimize its impact, suggesting possible neuroprotective properties of antipsychotics. The present study investigates the effects of chronic treatment with the atypical antipsychotic, risperidone, on locomotor sensitization in the subchronic phencyclidine-treated rat. METHODS: Rats were treated with phencyclidine sub-chronically (2 mg/kg bi-daily for one week followed by a one week wash-out period) or vehicle. Half of the phencyclidine group was concurrently treated with risperidone (0.5 mg/kg IP) twice daily for 15 days, beginning 3 days before the start of phencyclidine administration. 6 weeks after treatment all rats were injected with a phencyclidine-challenge (3.2 mg/kg) and immediately after their locomotor activity measured for 20 min. RESULTS: Co administration of risperidone at the time of phencyclidine administration significantly reduced the phencyclidine-challenge locomotor effect administered 6 weeks later. DISCUSSION: These results demonstrate that concurrent risperidone is neuroprotective, and clearly suggests its functionality can be translated to a clinical setting for treating the so-called prodrome. PMID- 26838119 TI - A Physicochemical Approach Toward Extending Conjugation and the Ordering of Solution-Processable Semiconducting Polymers. AB - Poly(3-hexylthiophene)s (P3HTs) were synthesized with a well-controlled molecular weight (Mw) and degree of regioregularity; additionally, pi-conjugated P3HT structures in both solutions and films were systematically investigated. Conjugated P3HT phases in spin-cast films significantly changed from ordered nanorods, -fibrils, and -ribbons to less-ordered granules, depending on the conformation of the P3HT chains in solutions. The chain conformations could be physicochemically adjusted by modifying chain lengths (from 5 to 45 kDa), solvents, and ultrasonication. Highly extended conformations of the P3HT in ultrasound-treated solutions yielded longer degree of conjugation both the intra- and intermolecularly. When toluene was used as a marginal solvent, ultrasonicated 0.1 wt % 29 kDa P3HT solutions could be used to yield highly ordered aggregates in spin-cast films, including nanoribbons or nanosheets, with field-effect mobility (MUFET) up to ~0.1 cm(2) V(-1) s(-1) being measured for organic field effect transistors (OFETs). However, ultrasonicated chloroform systems with good P3HT solubility (for P3HT Mw >= 20 kDa) yielded featureless conducting layers even at 0.4 wt % P3HT content. However, these film-based OFETs yielded MUFET values up to 0.04 cm(2) V(-1) s(-1), which were much greater than 0.004 cm(2) V( 1) s(-1) for the nonultrasonicated systems. PMID- 26838117 TI - Combinatorial release of dexamethasone and amiodarone from a nano-structured parylene-C film to reduce perioperative inflammation and atrial fibrillation. AB - Suppressing perioperative inflammation and post-operative atrial fibrillation requires effective drug delivery platforms (DDP). Localized anti-inflammatory and anti-arrhythmic agent release may be more effective than intravenous treatment to improve patient outcomes. This study utilized a dexamethasone (DEX) and amiodarone (AMIO)-loaded Parylene-C (PPX) nano-structured film to inhibit inflammation and atrial fibrillation. The PPX film was tested in an established pericardial adhesion rabbit model. Following sternotomy, the anterior pericardium was resected and the epicardium was abraded. Rabbits were randomly assigned to five treatment groups: control, oxidized PPX (PPX-Oxd), PPX-Oxd infused with DEX (PPX-Oxd[DEX]), native PPX (PPX), and PPX infused with DEX and AMIO (PPX[AMIO, DEX]). 4 weeks post-sternotomy, pericardial adhesions were evaluated for gross adhesions using a 4-point grading system and histological evaluation for epicardial neotissue fibrosis (NTF). Atrial fibrillation duration and time per induction were measured. The PPX[AMIO, DEX] group had a significant reduction in mean adhesion score compared with the control group (control 2.75 +/- 0.42 vs. PPX[AMIO, DEX] 0.25 +/- 0.42, P < 0.001). The PPX[AMIO, DEX] group was similar to native PPX (PPX 0.38 +/- 0.48 vs. PPX[AMIO, DEX] 0.25 +/- 0.42, P=NS). PPX-Oxd group adhesions were indistinguishable from controls (PPX-Oxd 2.83 +/- 0.41 vs. control 2.75 +/- 0.42, P=NS). NTF was reduced in the PPX[AMIO, DEX] group (0.80 +/- 0.10 mm) compared to control (1.78 +/- 0.13 mm, P < 0.001). Total duration of atrial fibrillation was decreased in rabbits with PPX[AMIO, DEX] films compared to control (9.5 +/- 6.8 s vs. 187.6 +/- 174.7 s, p = 0.003). Time of atrial fibrillation per successful induction decreased among PPX[AMIO, DEX] films compared to control (2.8 +/- 1.2 s vs. 103.2 +/- 178 s, p = 0.004). DEX/AMIO loaded PPX films are associated with reduced perioperative inflammation and a diminished atrial fibrillation duration. Epicardial application of AMIO, DEX films is a promising strategy to prevent post-operative cardiac complications. PMID- 26838120 TI - Local coordination and dynamics of a protic ammonium based ionic liquid immobilized in nano-porous silica micro-particles probed by Raman and NMR spectroscopy. AB - Room temperature ionic liquids confined in a solid material, for example, nano porous silica, are particularly propitious for energy related applications. The aim of this study is to probe the molecular interactions established between the protic ionic liquid diethylmethylammonium methanesulfonate (DEMA-OMs) and silica, where the latter consists of nano-porous micro-particles with pores in the size range of 10 nm. The changes in the local coordination and transport properties induced by the nano-confinement of the ionic liquid are investigated by a combination of Raman and solid-state NMR spectroscopy. In particular, one dimensional (1D) (1)H and (29)Si and two-dimensional (2D) (29)Si{(1)H} HETOCR solid-state NMR are combined to identify the sites of interaction at the silica ionic liquid interface. Pulsed field gradient (PFG) NMR experiments are performed to estimate the self-diffusion of both bulk and nano-confined DEMA-OMs. Complementary information on the overall coordination and interaction scheme is achieved by Raman spectroscopy. All these advanced experimental techniques are revealed to be crucial to differentiate between ionic liquid molecules residing in the inter- or intra-particle domains. PMID- 26838121 TI - Poor governance in the award of honours and degrees in British medicine: an extreme example of a systemic problem. PMID- 26838122 TI - Electron microscopy imaging of proteins on gallium phosphide semiconductor nanowires. AB - We have imaged GaP nanowires (NWs) incubated with human laminin, serum albumin (HSA), and blood plasma using both cryo-transmission electron microscopy and synchrotron based X-ray photoemission electron microscopy. This extensive imaging methodology simultaneously reveals structural, chemical and morphological details of individual nanowires and the adsorbed proteins. We found that the proteins bind to NWs, forming coronas with thicknesses close to the proteins' hydrodynamic diameters. We could directly image how laminin is extending from the NWs, maximizing the number of proteins bound to the NWs. NWs incubated with both laminin and HSA show protein coronas with a similar appearance to NWs incubated with laminin alone, indicating that the presence of HSA does not affect the laminin conformation on the NWs. In blood plasma, an intermediate sized corona around the NWs indicates a corona with a mixture of plasma proteins. The ability to directly visualize proteins on nanostructures in situ holds great promise for assessing the conformation and thickness of the protein corona, which is key to understanding and predicting the properties of engineered nanomaterials in a biological environment. PMID- 26838125 TI - In memoriam: the contributions to public health research of Farah Jamal, BA, MSc, PhD. PMID- 26838126 TI - Setbacks in the process of assimilation of problematic experiences in two cases of emotion-focused therapy for depression. AB - OBJECTIVE: Research on the assimilation model has suggested that psychological change takes place in a sequence of stages punctuated by setbacks, that is, by transient reversals in the developmental course. This study analyzed such setbacks in one good outcome case and one poor outcome case of Emotion-focused therapy (EFT) for depression. METHOD: Intensive analyses of five transcribed sessions from each case identified 26 setbacks in the good outcome case and 27 in the poor outcome case. The reason for each setback was classified into one of four categories: balance strategy, exceeding the therapeutic zone of proximal development either induced by the therapist (ZPD-T) or induced by the client (ZPD C), or spontaneous switches. RESULTS: In the good outcome case the most frequent reasons for setbacks were balance strategy and spontaneous switches, whereas in the poor outcome case the most frequent reason for setbacks was ZPD-T. CONCLUSIONS: As in previously studied therapies, setbacks in EFT, usually represent productive work on relatively less advanced strands of the client's major problems. Results point to the importance of the therapist attending to the limits of the client's therapeutic ZPD. PMID- 26838127 TI - Assessing the Growth of Bioactive Compounds and Scaffolds over Time: Implications for Lead Discovery and Scaffold Hopping. AB - The increase in compounds with activity against five major therapeutic target families has been quantified on a time scale and investigated employing a compound-scaffold-cyclic skeleton (CSK) hierarchy. The analysis was designed to better understand possible reasons for target-dependent growth of bioactive compounds. There was strong correlation between compound and scaffold growth across all target families. Active compounds becoming available over time were mostly represented by new scaffolds. On the basis of scaffold-to-compound ratios, new active compounds were structurally diverse and, on the basis of CSK-to scaffold ratios, often had previously unobserved topologies. In addition, novel targets emerged that complemented major families. The analysis revealed that compound growth is associated with increasing chemical diversity and that current pharmaceutical targets are capable of recognizing many structurally different compounds, which provides a rationale for the rapid increase in the number of bioactive compounds over the past decade. In light of these findings, it is likely that new chemical entities will be discovered for many small molecule targets including relatively unexplored ones as well as for popular and well studied therapeutic targets. Moreover, given the wealth of new "active scaffolds" that have been increasingly identified for many targets over time, computational scaffold-hopping exercises should generally have a high likelihood of success. PMID- 26838128 TI - Epstein-Barr virus-associated diffuse large B-cell lymphoma: diagnosis, difficulties and therapeutic options. AB - Epstein Barr Virus (EBV)-positive diffuse large B cell lymphoma (DLBCL) most frequently affects elderly patients, without previous immunosuppression, with frequent extra-nodal involvement and whose disease runs an aggressive clinical course with high International Prognostic Index (IPI) scores. Various EBV-related transforming mechanisms, much favored by immunosenescence, have been described, including activation of the NFKB transcriptional program. Elderly patients show poor survival after treatment with conventional CHOP regimens, even after addition of Rituximab. Younger patients, however, have a better outcome with a similar prognosis to EBV-negative DLBCL cases. New therapeutic strategies, including treatments targeting EBV, new drugs directed against specific pathways constitutively activated in these lymphomas, and new specific conjugate antibodies against molecules usually expressed in the tumor cells, such as CD30, are described. PMID- 26838129 TI - Conformational dynamics is key to understanding loss-of-function of NQO1 cancer associated polymorphisms and its correction by pharmacological ligands. AB - Protein dynamics is essential to understand protein function and stability, even though is rarely investigated as the origin of loss-of-function due to genetic variations. Here, we use biochemical, biophysical, cell and computational biology tools to study two loss-of-function and cancer-associated polymorphisms (p.R139W and p.P187S) in human NAD(P)H quinone oxidoreductase 1 (NQO1), a FAD-dependent enzyme which activates cancer pro-drugs and stabilizes several oncosuppressors. We show that p.P187S strongly destabilizes the NQO1 dimer in vitro and increases the flexibility of the C-terminal domain, while a combination of FAD and the inhibitor dicoumarol overcome these alterations. Additionally, changes in global stability due to polymorphisms and ligand binding are linked to the dynamics of the dimer interface, whereas the low activity and affinity for FAD in p.P187S is caused by increased fluctuations at the FAD binding site. Importantly, NQO1 steady-state protein levels in cell cultures correlate primarily with the dynamics of the C-terminal domain, supporting a directional preference in NQO1 proteasomal degradation and the use of ligands binding to this domain to stabilize p.P187S in vivo. In conclusion, protein dynamics are fundamental to understanding loss-of-function in p.P187S, and to develop new pharmacological therapies to rescue this function. PMID- 26838130 TI - A comparison of the dose from natural radionuclides and artificial radionuclides after the Fukushima nuclear accident. AB - Due to the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident, the evacuees from Namie Town still cannot reside in the town, and some continue to live in temporary housing units. In this study, the radon activity concentrations were measured at temporary housing facilities, apartments and detached houses in Fukushima Prefecture in order to estimate the annual internal exposure dose of residents. A passive radon-thoron monitor (using a CR-39) and a pulse-type ionization chamber were used to evaluate the radon activity concentration. The average radon activity concentrations at temporary housing units, including a medical clinic, apartments and detached houses, were 5, 7 and 9 Bq m(-3), respectively. Assuming the residents lived in these facilities for one year, the average annual effective doses due to indoor radon in each housing type were evaluated as 0.18, 0.22 and 0.29 mSv, respectively. The average effective doses to all residents in Fukushima Prefecture due to natural and artificial sources were estimated using the results of the indoor radon measurements and published data. The average effective dose due to natural sources for the evacuees from Namie Town was estimated to be 1.9 mSv. In comparison, for the first year after the FDNPP accident, the average effective dose for the evacuees due to artificial sources from the accident was 5.0 mSv. Although residents' internal and external exposures due to natural radionuclides cannot be avoided, it might be possible to lower external exposure due to the artificial radionuclides by changing some behaviors of residents. PMID- 26838131 TI - Evaluation of the relative biological effectiveness of spot-scanning proton irradiation in vitro. AB - Variations in relative biological effectiveness (RBE) from a fixed value of 1.1 are critical in proton beam therapy. To date, studies estimating RBE at multiple positions relative to the spread-out Bragg peak (SOBP) have been predominantly performed using passive scattering methods, and limited data are available for spot-scanning beams. Thus, to investigate the RBE of spot-scanning beams, Chinese hamster fibroblast V79 cells were irradiated using the beam line at the Hokkaido University Hospital Proton Therapy Center. Cells were placed at six different depths, including the entrance of the proton beam and the proximal and distal part of the SOBP. Surviving cell fractions were analyzed using colony formation assay, and cell survival curves were obtained by the curve fitted using a linear quadratic model. RBE10 and RBE37 were 1.15 and 1.21 at the center of the SOBP, respectively. In contrast, the distal region showed higher RBE values (1.50 for RBE10 and 1.85 for RBE37). These results are in line with those of previous studies conducted using passive scattering proton beams. Taken together, these data strongly suggest that variations in RBE should be considered during treatment planning for spot-scanning beams as well as for passive scattering proton beams. PMID- 26838136 TI - Modelling the epidemiology of Escherichia coli ST131 and the impact of interventions on the community and healthcare centres. AB - ST131 Escherichia coli is an emergent clonal group that has achieved successful worldwide spread through a combination of virulence and antimicrobial resistance. Our aim was to develop a mathematical model, based on current knowledge of the epidemiology of ESBL-producing and non-ESBL-producing ST131 E. coli, to provide a framework enabling a better understanding of its spread within the community, in hospitals and long-term care facilities, and the potential impact of specific interventions on the rates of infection. A model belonging to the SEIS (Susceptible-Exposed-Infected-Susceptible) class of compartmental models, with specific modifications, was developed. Quantification of the model is based on the law of mass preservation, which helps determine the relationships between flows of individuals and different compartments. Quantification is deterministic or probabilistic depending on subpopulation size. The assumptions for the model are based on several developed epidemiological studies. Based on the assumptions of the model, an intervention capable of sustaining a 25% reduction in person-to person transmission shows a significant reduction in the rate of infections caused by ST131; the impact is higher for non-ESBL-producing ST131 isolates than for ESBL producers. On the other hand, an isolated intervention reducing exposure to antimicrobial agents has much more limited impact on the rate of ST131 infection. Our results suggest that interventions achieving a continuous reduction in the transmission of ST131 in households, nursing homes and hospitals offer the best chance of reducing the burden of the infections caused by these isolates. PMID- 26838137 TI - Long term marijuana use is linked to impaired verbal memory. PMID- 26838138 TI - In reply: Nasotracheal intubation with airway scope. PMID- 26838139 TI - S-1-based regimens for locally advanced/metastatic non-small-cell lung cancer: a meta-analysis. AB - AIM: We performed a meta-analysis of S-1-containing regimens versus control in the management of locally advanced/metastatic non-small-cell lung cancer. METHODOLOGY: Eligible studies included randomized studies evaluating S-1 containing regimens in the settings of locally advanced, first-line metastatic or second-line metastatic non-small-cell lung cancer. RESULTS: Pooled odds ratio for overall response rate was 1.09 (95% CI: 0.85-1.38; p = 0.2), the pooled hazard ratio for progression-free survival was 0.98 (95% CI: 0.88-1.09; p = 0.69) and the pooled hazard ratio for overall survival was 0.98 (95% CI: 0.88-1.10; p = 0.75) for S-1-based regimens versus control. Moreover, the relative risk of febrile neutropenia was 0.34 (95% CI: 0.20-0.59; p = 0.0001). CONCLUSION: Our meta-analysis has demonstrated that S-1-based regimens are associated with similar efficacy outcomes and better hematological tolerability. PMID- 26838140 TI - Publicationomics: Delusion demystified. PMID- 26838141 TI - Effect of fixed space maintainers and removable appliances on oral microflora in children: An in vivo study. AB - BACKGROUND: Oral habits and caries if left untreated may result in crowding and arch length discrepancy in developing dentition. Therefore, appliances are used to maintain the arch length and for proper relationship between dental arches. However, its insertion may cause an increase in bacterial concentration. AIM: This study aimed to evaluate the growth of Streptococcus mutans, Lactobacillus sp., and Candida albicans in saliva during the first 6 months of orthodontic therapy. MATERIALS AND METHODS: Twenty children in the age group of 6-15 years were selected with regard to indication of orthodontic treatment, and subsequently grouped as patients to be treated with fixed space maintainers or removable appliances. Unstimulated saliva was collected in a sterile container at baseline and at 1-month, 3-month, and 6-month recalls for every selected child. Samples collected were processed for bacterial culture in different culture media at different time intervals. STATISTICAL ANALYSIS: SPSS (Statistical Package for Social Sciences) Version 15.0 statistical software was carried for bacterial counts. Chi-square test and t-test were performed to know the effects of each variable and to reveal the statistical significance. RESULT: Bacterial counts of Streptococcus mutans, Lactobacillus sp., and Candida albicans were found to be statistically significant (P 0<= 0.001), (P < 0.05), and (P < 0.001), respectively in both the groups at all intervals. CONCLUSION: At different time intervals, the total numbers of bacterial count of Streptococcus mutans were comparatively higher, followed by Lactobacillus sp. and Candida albicans. PMID- 26838142 TI - pH modulation and salivary sugar clearance of different chocolates in children: A randomized clinical trial. AB - BACKGROUND: Sugars that occur naturally in foods and those added in processed foods may act as the source for fermentable carbohydrates and may initiate caries process. Among all the foods consumed by children, chocolates form an important constituent. A wide variety of chocolates are available in the Indian market and very few studies have compared their acidogenicity and salivary sugar clearance. OBJECTIVES: To compare the acidogenicity and salivary sugar clearance of 6 different commercially available chocolates in the Indian market. MATERIALS AND METHODS: Thirty subjects aged 10-15 years were selected randomly from one of the available public schools in Nellore city. Six commercially available chocolates in the Indian market were divided into three groups, unfilled (dark and milk chocolate), filled (wafer and fruit and nuts chocolate), and candy (hard milk and mango-flavored candy) groups. Plaque pH values and salivary sugar clearance rates are assessed at baseline, 5, 10, 15, 20, and 30 min after consumption. All the data obtained were statistically evaluated using independent sample t-test and one-way ANOVA for multiple group comparisons. RESULTS: Mango-flavored candy had maximum fall in plaque pH and least fall in plaque pH was recorded with milk chocolate. Fruit and nuts chocolate had a maximum clearance of salivary sugar and least fall in the salivary sugar clearance was recorded with dark chocolate. When the plaque pH and salivary sugar clearance of all the chocolates were assessed, it was seen that the values were statistically significant at all the time intervals (P < 0.05). CONCLUSION: Dark chocolate had a high fall in pH and milk chocolate had low salivary sugar clearance which signifies that unfilled chocolates are more cariogenic than other chocolates. Even though mango-flavored candy had maximum fall in plaque pH, its salivary sugar clearance was high. PMID- 26838143 TI - Correlation of plaque nitric oxide levels with plaque Streptococcus mutans, plaque pH and decayed, missing and filled teeth index of children of different age groups. AB - CONTEXT: Dental plaque is considered one of the most important etiological factors for dental caries. Nitrate and Nitrite levels in saliva are considered protective against oral and gastrointestinal disease. Plaque nitric oxide (NO) levels and its role in dental caries has not be explored in the literature. AIM: Determine the correlation of the plaque nitric oxide (NO) with dental caries in vivo. MATERIALS AND METHOD: 75 healthy children between ages of 3-15 years were selected. The age, state of dentition and the level of caries in all individuals were determined by the same examiner, using DMFT/deft index. The plaque samples collected were subjected to nitric oxide estimation, streptococcus mutans count and pH for correlation. STATISTICAL ANALYSIS USED: SPSS computer based software was used for descriptive data analysis. ANOVA one way analysis and Karl pearson's correlation was carried out. RESULTS AND CONCLUSION: Statistically significant relationship was observed between plaque nitric oxide and dental caries in all age groups. Similarly, significant correlation of nitric oxide was found in relation to plaque streptococcus mutans and plaque pH. Thus concluded, plaque nitric oxide can be considered as a risk assessment tool for prediction of dental caries. PMID- 26838144 TI - An in-vitro evaluation of antibacterial effect of Amalgomer CR and Fuji VII against bacteria causing severe early childhood caries. AB - OBJECTIVE: To evaluate the antibacterial action of Amalgomer CR and Fuji VII against bacteria causing S-early childhood caries. MATERIALS AND METHODS: Antibacterial activity of Amalgomer CR and Fuji VII was assessed using the agar diffusion test in triplicate. The powder and liquid of each test material was mixed and inserted in the punched wells (6 mm * 2 mm). A composition of 0.2% chlorhexidine digluconate acted as control. The agar plates were incubated at 37 degrees C for 24 h for Streptococcus mutans, S. salivarius, S. parasanguinis and Actinomyces viscosus, whereas Lactobacillus casei was incubated for 48 h. Sizes of the inhibition zones were calculated by subtracting the diameter of the specimen (6 mm) from the average of the three measurements of the halo. For each test material against each bacteria, 9 measurements were made (3 measurements * 3 times). Kruskal-Wallis test was done to compare the zones of inhibition of test materials against individual bacteria. Pair-wise comparison was done by Mann Whitney U-test. RESULTS: Amalgomer CR had the most antibacterial against S. mutans (31.0 mm), followed by A. viscosus (21.87 mm), S. salivarius (13.87 mm), S. parasanguinis (10.80 mm), and L. casei (9.69 mm). Fuji VII had the most antibacterial action against S. salivarius (10.65 mm), followed by A. viscosus (9.10 mm). However, it did not inhibit the growth of S. mutans (0 mm), S. parasanguinis (0 mm), and L. casei (0 mm). CONCLUSION: Amalgomer CR and Fuji VII showed wide variation in antibacterial action against all test organisms. PMID- 26838145 TI - A survey of the dentist attire and gender preferences in dentally anxious children. AB - BACKGROUND: Anxiety about doctors among children is very common. White coat phobia which is a classical conditioning phenomenon is said to be prevalent among children. OBJECTIVES: To analyze the association between anxious states of children about dentists and their preference of dentist attire and gender in the dental office. MATERIALS AND METHODS: The 9-12-year-old middle school children were selected for the study. Children were asked to fill a questionnaire containing children's fear survey schedule-dental subscale (CFSS-DS) and asked to prefer dental attire from four different pictures displaying the single anonymous dentist in four different attires in the same operator. The CFSS-DS gave the anxiety scale, and age, gender, and experience were also plotted against children preference in an apron, protective wear, and gender preference. Results were tabulated and statistically analyzed using Chi-square test. RESULTS: About 718 (62%) were scored as anxious children. Of all anxious children, 502 (69.9%) had preference of colored attires of the dentist, and 408 (66.8%) anxious children preferred dentist with protective wear. Female dentists were preferred by 452 (66%) anxious children. Same gender preference was also prevalent. PMID- 26838146 TI - Association of severe early childhood caries with iron deficiency anemia. AB - BACKGROUND: Severe tooth decay is known to affect the health and well-being of young children. However, there has been minimal research showing the association of severe early childhood caries (S-ECC) and iron deficiency anemia (IDA). AIMS: The primary aim of this study was to investigate an association between S-ECC with IDA. The secondary objective was to find an association between severe caries and body weight of the child. The oral health-related quality of life of children with S-ECC was also assessed. MATERIALS AND METHODS: Following the ethical approval, 60 children aged 2-6 years (30 with S-ECC and 30 controls with caries status <2) were recruited for this cross-sectional association study. Each child received a clinical examination for dental caries status using deft index and a blood investigation to determine various parameters; hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration, and packed cell volume (PCV). Children underwent venipuncture after due parental consent, and 2.5 mL blood was collected from each child to evaluate the above parameters. Following this, the parents filled up a 10 point questionnaire to determine the child's quality of life. Data were then analyzed by t-test and Fischer's exact t test. RESULT: On comparison of percentage of children with IDA in S-ECC and control group, it was found that children with S-ECC were more likely to have IDA odds ratio (95% confidence interval): 10.77 (2.0, 104.9), (P = 0.001). In addition to this, S-ECC children were significantly more likely to have low Hb, MCV, and PCV levels (P < 0.001) which imply that S-ECC may be a risk marker for the development of anemia. More children (93%) with severe caries were found to have less body weight than ICMR standard weight for age as compared to children with low caries (P < 0.05%). CONCLUSION: S-ECC is strongly associated with the anemia due to iron deficiency, and efforts should be made toward the preventive and curative aspects of ECC, which may improve the general well-being and quality of life of a child. PMID- 26838147 TI - Impact of verbal, Braille text, and tactile oral hygiene awareness instructions on oral health status of visually impaired children. AB - BACKGROUND: Visually impaired children face limitations in interacting with the environment, as they cannot see the facial expression of parents, teachers and cannot perceive social behavior. These children are challenged every day in learning basic life skills and maintenance of oral hygiene being one among them. AIM: To evaluate the impact of verbal, braille text, and tactile oral hygiene awareness instructions on oral health status of visually impaired children. MATERIALS AND METHODS: One hundred and twenty institutionalized visually impaired children aged 6-16 years were selected and divided into three groups (40 children each). Group I: Verbal and tactile, Group II: Verbal and braille, Group III: Verbal, braille, and tactile. Instructions regarding maintenance of good oral hygiene and brushing technique were explained to all the children, and oral health status of these children using plaque index (Silness and Loe) and gingival index (Loe and Silness) was evaluated at 1, 3, and 6 months interval. STATISTICAL ANALYSIS: ANOVA test was used to analyze the intra- and inter-group comparisons and Tukey post-hoc test for multiple group comparisons. RESULTS: Children in all the groups showed reduction in plaque and gingival scores. There was the highest percentage of reduction in plaque scores in Group III (70.6%), and the decrease in gingival scores was the highest in Group II (84%). CONCLUSION: Severity of dental plaque and gingivitis in visually impaired individuals can be reduced by a controlled and supervised educational program. The combination of all three, i.e., verbal, braille, and tactile mode of oral health educational aids proved to be effective. PMID- 26838148 TI - Cheiloscopy and dermatoglyphics as genetic markers in the transmission of cleft lip and palate: A case-control study. AB - BACKGROUND: Determining the relative risk of cleft lip and palate (CL[P]) on the basis of lip prints and dermatoglyphics as genetic background may be useful for genetic counseling, and the development of future preventive measures. AIMS AND OBJECTIVES: (1) To analyze the various pattern types of lip prints and dermatoglyphics in parents of CL(P) children and to detect if any specific type can be contemplated as a genetic marker in the transmission of CL(P). (2) To compare these patterns with that of parents of unaffected children. MATERIALS AND METHODS: 31 parents of children with CL(P) as a study group, and 31 parents of unaffected children as control group were included. Lip prints and finger prints were collected from all subjects and analysis of both patterns was carried out followed by a comparison of the patterns of unaffected parents with the controls statistically. RESULTS: Among the mothers of the study group, type O followed by type IIa lip patterns were found to be significantly higher in upper and lower lips, and in fathers type IIa followed by type O were significantly higher. In the control group, type IIb followed by type III were higher in both fathers and mothers. Dermatoglyphic analysis of palm and finger prints revealed no significant difference in the pattern types and total ridge counts, but the Atd angle asymmetry was found to be significant between study and control group. CONCLUSION: Types IIa and O lip patterns, asymmetry of Atd angles can be considered as genetic markers for the transmission of CL(P) deformity to offsprings. PMID- 26838149 TI - A clinical and radiographic study of four different root canal fillings in primary molars. AB - BACKGROUND: Successful treatment of infected primary teeth aims to preserve the child's health. However, the complex morphology of primary root canals and the desire for shorter therapy sessions put the necessity to search for the ideal root canal paste. AIMS: To evaluate pulpectomy of nonvital primary molars using four different root canal filling pastes zinc oxide and propolis (ZOP) as a new paste, endoflas-chlorophenol-free as a new paste free of chlorophenol, metapex paste, and zinc oxide and eugenol (ZOE) paste as a control paste. MATERIALS AND METHODS: Pulpectomy of 64 nonvital primary molars were accomplished in 39 children aged 3-9 years. Teeth were randomly divided into four equal groups of 16 molars according to the type of root canal filling. Pulpectomy was performed in one stage using 5.25% sodium hypochlorite irrigation and stainless-steel crown for final restoration. Clinical and radiographic results were evaluated double blindly for two periods of 6, 12 months. Data were analyzed using Chi square/Fisher's exact test, and P-value was set as 0.05. RESULTS: The four pastes achieved convergent clinical and radiographic success within the two observation periods (P > 0.05). ZOE paste was the slowest in its resorption. CONCLUSIONS: ZOP is a promising paste with its natural antibacterial component (propolis). ZOE paste had convergent efficacy to the other pastes. PMID- 26838150 TI - Effect of the video output of the dental operating microscope on anxiety levels in a pediatric population during restorative procedures. AB - BACKGROUND: Adapting a child to the alien settings of a dental operatory is a major challenge to the dentist. Fear of the unknown and preconceived notions of dental pain causes anxiety in the pediatric patient. This often leads to disruptive and uncooperative behavior in the dental operatory. Many methods of behavior management have been described, of which the Tell-Show-Do (TSD) is an established and time-tested technique of behavior management. AIM: To determine if a live visual output of the dental operating microscope (DOM) could be used as an adjunct to the TSD technique, to involve the child more completely in the procedure and reduce the fear of the unknown. MATERIALS AND METHODS: The study was a randomized, controlled, crossover, and cross-sectional clinical trial. Data were obtained from two visits. 90 children having carious lesions on both lower first molars, in the 7-9 years age group were selected and divided randomly into two groups. Restorative procedures were performed on one tooth per visit, with visits 1 week apart. Live display of the procedure was shown to the patient using video output of the DOM displayed on a 72 inch LCD monitor, angled for best visibility of the child. Anxiety levels were evaluated using Venhams picture selection test and pulse oximetry. STATISTICAL ANALYSIS: Student's t-test was used to compare the anxiety scores obtained from the two groups. RESULTS: The results showed there was a decrease in the anxiety from the first visit to the second visit. (P = 0.05 for Group A and P = 0.003 for Group B). The patients preferred the visit in which the DOM was used. The operator reported an increased patient compliance and reduced patient movement in the visits in which the DOM was used. CONCLUSION: There is a reduction in anxiety from the first visit to the second visit for restorative treatment when the DOM is used. PMID- 26838151 TI - Anti-microbial efficacy of green tea and chlorhexidine mouth rinses against Streptococcus mutans, Lactobacilli spp. and Candida albicans in children with severe early childhood caries: A randomized clinical study. AB - INTRODUCTION: Green tea is a beverage which is consumed worldwide and is reported to have anti-cariogenic effect. So, if it was as effective as chlorhexidine (CHX) mouth rinse against cariogenic microbes it could be considered a natural, economical alternative. The purpose of this study was to evaluate and compare the anti-microbial efficacy of 0.5% green tea and 0.2% CHX mouth rinses against Streptococcus Mutans, Lactobacilli spp. and Candida Albicans. MATERIALS AND METHODS: 30 children aged 4-6 years with S-ECC (based on defs score) were selected. Children were divided randomly into 2 equal groups and were asked to rinse with the prescribed mouth rinse once daily for 2 weeks after breakfast under supervision. A base-line and post rinsing non-stimulated whole salivary sample (2 ml) was collected and tested for the number of colony forming units. The data was statistically analyzed using SPSS v16.0 software with one-way ANOVA and Tukey's POSTHOC test. RESULTS: A statistically significant fall in colony count was found with both the mouth rinses in Streptococcus Mutans (P < 0.001, P < 0.001) and lactobacilli (P < 0.001, P < 0.001) but not against Candida albicans (P = 0.264, P = 0.264). Against Streptococcus Mutans, green tea mouth rinse was found to be significantly better than CHX mouth rinse (P = 0.005). Against lactobacilli spp, CHX mouth rinse was significantly better than green tea mouth rinse (P < 0.001). CONCLUSION: Green tea mouth rinse can be considered safe, economical and used without much concern. However, further studies are recommended. PMID- 26838152 TI - Comparison of linear and zero-inflated negative binomial regression models for appraisal of risk factors associated with dental caries. AB - CONTEXT: Dental caries among children has been described as a pandemic disease with a multifactorial nature. Various sociodemographic factors and oral hygiene practices are commonly tested for their influence on dental caries. In recent years, a recent statistical model that allows for covariate adjustment has been developed and is commonly referred zero-inflated negative binomial (ZINB) models. AIM: To compare the fit of the two models, the conventional linear regression (LR) model and ZINB model to assess the risk factors associated with dental caries. MATERIALS AND METHODS: A cross-sectional survey was conducted on 1138 12 year-old school children in Moradabad Town, Uttar Pradesh during months of February-August 2014. Selected participants were interviewed using a questionnaire. Dental caries was assessed by recording decayed, missing, or filled teeth (DMFT) index. STATISTICAL ANALYSIS USED: To assess the risk factor associated with dental caries in children, two approaches have been applied - LR model and ZINB model. RESULTS: The prevalence of caries-free subjects was 24.1%, and mean DMFT was 3.4 +/- 1.8. In LR model, all the variables were statistically significant. Whereas in ZINB model, negative binomial part showed place of residence, father's education level, tooth brushing frequency, and dental visit statistically significant implying that the degree of being caries-free (DMFT = 0) increases for group of children who are living in urban, whose father is university pass out, who brushes twice a day and if have ever visited a dentist. CONCLUSION: The current study report that the LR model is a poorly fitted model and may lead to spurious conclusions whereas ZINB model has shown better goodness of fit (Akaike information criterion values - LR: 3.94; ZINB: 2.39) and can be preferred if high variance and number of an excess of zeroes are present. PMID- 26838153 TI - Dental health in children with congenital bleeding disorders in and around Davangere: A case-control study. AB - AIM: The present study was carried out to investigate the dental and some other aspects of oral health status of young patients with congenital bleeding disorders (CBDs) and compared with controls. MATERIALS AND METHODS: Decayed, missed, filled tooth surfaces (DMFS-dmfs) in permanent and primary teeth scores, simplified oral hygiene index, occlusion, occurrence of hypoplasia, fluorosis other hard tissue and soft tissue findings of 50 CBD patients at the age range of 4-15 years and 50 of other children as control were compared. Data were analyzed by Chi-square and Student's unpaired t-test. RESULTS: Patients were significantly more caries-free with less decayed teeth in primary-permanent dentition (P < 0.05) and with lower scores for overall hygiene. CONCLUSION: By this, it can be concluded that children with CBD have a significantly lower prevalence of dental caries and better oral hygiene compared with matched, healthy controls. PMID- 26838154 TI - Self healing hemophilic pseudotumor of the mandible in a 5-year-old boy, an interesting and rare finding: Case report and review. AB - Hemophilic pseudotumor (PT) is a very rare complication of hemophilia consisting of a chronic, encapsulated, hemorrhagic fluid collection occurring both in the soft tissues and/or bone. Radiological features of osseous hemophilic PT are nonspecific and mimic several other benign or malignant bone tumors or infectious processes. Although the diagnosis is usually made on the location of the lesion and by the knowledge of the underlying disease, the radiologist should be aware of the imaging characteristics, in order to avoid misinterpretation as a malignant tumor, as biopsy of these lesions is contraindicated. PMID- 26838155 TI - Central hemangioma: A case report and review of literature. AB - Hemangioma is a benign self-involuting tumor of endothelial cells. They are the most common benign congenital lesions in humans and are characterized by the proliferation of blood vessels. They are often present at birth or appear soon after, and grow rapidly by endothelial proliferation. This article presents a rare case of central hemangioma occurring in the mandible of a 13-year-old boy, and a brief review on clinical, radiological, and histopathological characteristics of central hemangiomas. PMID- 26838156 TI - Fetal hydantoin syndrome: A case report. AB - Fetal hydantoin syndrome (FHS) is a spectrum of defects caused to the developing fetus by exposure to the teratogenic effects of antiepileptic drug (AED) phenytoin during pregnancy. Its clinical manifestations include limb abnormalities, ocular defects, central nervous system anomalies, intrauterine growth restriction, and hand and phalangeal anomalies. This case report presents an 8-year-old child born to an epileptic mother with a history of AED therapy, with features suggestive of FHS. PMID- 26838158 TI - A tribute. AB - Dr. Kapil Rajiv Sharma, who was working as the Professor and head of the Department of Pediatric Dentistry at H. P. Government Dental College and Hospital, Shimla, left for heavenly abode on June 19, 2015, following a massive cardiac arrest during the duty hours at Indira Gandhi Medical College (IGMC), Shimla. His death is an irreparable loss to the department and to the family, which can never be compensated by any means. He was gifted with a charismatic personality filled with good human qualities,immense values and tremendous contribution to his subject and department. This kind-hearted man will always be remembered for his noble deeds, who left an indelible impression on everyone. PMID- 26838157 TI - Dental root agenesis following radiation and antineoplastic therapy: A Case Report. AB - The survival rates of patients suffering from various childhood neoplasms have improved dramatically with the advent of chemo-radiation therapy. The harmful effects of chemo-radiation therapy in the oro-facial region such as root agenesis, short roots, impaired amelogenesis, dentinogenesis, radiation caries, and other soft tissue pathologies are well recognized. In spite of these documented risks, the antineoplastic treatment modalities continue to serve the patient for overall improvement in survival and quality of life. However, a thorough understanding of the growth and development process and its relation with the complex antineoplastic treatment is very important for all clinicians. Such awareness could significantly improve the status of patients in the posttreatment period with the implementation of proper preventive and interceptive measures. This article intends to document a case of root agenesis that developed secondary to chemo-radiation therapy in a 12-year-old girl. PMID- 26838159 TI - Raman and DFT study of methimazole chemisorbed on gold colloidal nanoparticles. AB - The adsorption of methimazole on gold colloidal nanoparticles was investigated using a combination of surface-enhanced Raman scattering and density functional theory calculations, which allowed identifying the thiolate anion as the molecular species chemically interacting with the active sites of the gold surface, modeled as zero-charge metal adatoms, only through the sulfur atom. This result can be important for the use of these ligand/metal nanohybrids in the process of drug delivery. Moreover, functionalized gold nanoparticles are able to promote the Raman enhancement in the red-light region as well as in the near infrared, where generally no fluorescence emission occurs. This paves the way for the use of these nanosystems in a biological environment, even in vivo experiments. PMID- 26838161 TI - Liposome containing cinnamon oil with antibacterial activity against methicillin resistant Staphylococcus aureus biofilm. AB - The global burden of bacterial disease remains high and is set against a backdrop of increasing antimicrobial resistance. There is a pressing need for highly effective and natural antibacterial agents. In this work, the anti-biofilm effect of cinnamon oil on methicillin-resistant Staphylococcus aureus was evaluated. Then, cinnamon oil was encapsulated in liposomes to enhance its chemical stability. The anti-biofilm activities of the liposome-encapsulated cinnamon oil against MRSA biofilms on stainless steel, gauze, nylon membrane and non-woven fabrics were evaluated by colony forming unit determination. Scanning electron microscopy and laser scanning confocal microscopy analyses were employed to observe the morphological changes in MRSA biofilms treated with the encapsulated cinnamon oil. As a natural and safe spice, the cinnamon oil exhibited a satisfactory antibacterial performance on MRSA and its biofilms. The application of liposomes further improves the stability of antimicrobial agents and extends the action time. PMID- 26838160 TI - Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats. AB - Aditoprim (ADP) is a newly developed antibacterial agent in veterinary medicine. The metabolism and disposition of ADP in swine, broilers, carp and rats were investigated by using a radio tracer method combined with a radioactivity detector and a liquid chromatography/ion trap/time-of-flight mass spectrometry. After a single oral administration, more than 94% of the dose was recovered within 14 d in the four species. The urine excretion was dominant in swine and rats, making up 78% of the dose. N-monodesmethyl-ADP, N-didesmethyl-ADP, and 10 new metabolites were characterized. These metabolites were biotransformed from the process of demethylation, alpha-hydroxylation, N-oxidation, and NH2 glucuronidation. After an oral dose for 7 d, ADP-derived radioactivity was widely distributed in tissues, and high concentrations were especially observed in bile, liver, kidney, lung, and spleen. The radioactivity in the liver was eliminated much more slowly than in other tissues, with a half-life of 4.26, 3.38, 6.69, and 5.21 d in swine, broilers, carp, and rats, respectively. ADP, N-monodesmethyl ADP, and N-didesmethyl-ADP were the major metabolites in edible tissues. Notably, ADP was detected with the highest concentration and the longest duration in these tissues. These findings indicated that ADP is the marker residue and the liver is the residue target tissue. PMID- 26838162 TI - Pharmacokinetic Time Course Scaling of a Subcutaneously Administered Pegylated Peptide Conjugate for a First-in-Human Investigation. AB - BACKGROUND AND PURPOSE: Predicting absorption of macromolecules in humans following subcutaneous administration is complicated by interspecies differences in skin anatomy. The objective of this research was to test the hypothesis that an empiric relationship exists between non-human primates (NHPs) and humans in the absorption of a subcutaneously administered macromolecule which was then used to predict the time course of a pegylated peptide conjugate for planning of a first-in-human investigation. METHODS: Concentration data obtained from NHPs receiving intravenous and subcutaneous doses of a novel pegylated peptide conjugate were fit to a pharmacokinetic model. The model was then scaled to a virtual population of humans through incorporation of allometric scaling factors on clearance, volume and first-order rate absorption processes. Several scenarios of simulated data were compared with observed data obtained from a first-in-human investigation. RESULTS: NHP data were best described by a 2-compartment model with dual-parallel, first-order absorption processes, one of which exhibited a lag time. Empirically selected scaling factors, assuming an inverse relationship of body weight and absorption provided reasonable prediction of the peptide's time course in plasma. Employing fitted exponents based on observed human data improved the fit somewhat, however, did not correct entirely for over prediction observed with the empiric exponents. CONCLUSION: For macromolecules where the absorption can be described by first-order rate processes, an assumption of an inverse relationship in species size may predict the time course after subcutaneous administration and may support optimal study design for a first-in human investigation. PMID- 26838163 TI - Hepatitis E in Transplantation. AB - Hepatitis E virus (HEV) has a worldwide distribution and is known to cause acute and fulminant hepatitis. However, over the last few years, it has been shown to also cause chronic hepatitis and cirrhosis in immunosuppressed patients, especially solid-organ-transplant patients. In immunocompetent and immunosuppressed patients, HEV is also associated with extra-hepatic manifestations, such as neurological symptoms and kidney injury. Unfortunately, a diagnostic assay for HEV infection is still not available in all countries. Reduction of immunosuppression is the first-line therapeutic option for organ transplant patients with chronic hepatitis. In addition, ribavirin is highly efficient at treating chronic HEV infection. In this comprehensive review, we summarize the current knowledge regarding HEV diagnosis, its natural history, clinical manifestations, and treatments in patients with a solid-organ transplant. PMID- 26838164 TI - GSK-3beta downregulates Nrf2 in cultured cortical neurons and in a rat model of cerebral ischemia-reperfusion. AB - The NF-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway plays a critical role in protecting against oxidative stress in brain ischemia and reperfusion injury. Glycogen synthase kinase 3beta (GSK-3beta) may play a critical role in regulating Nrf2 in a Kelch-like ECH-associated protein 1 (Keap1) independent manner. However, the relationship between GSK-3beta and Nrf2 in brain ischemia and reperfusion injury is not clear. In this study, we explored the mechanisms through which GSK-3beta regulates Nrf2 and Nrf-2/ARE pathways in vitro and in vivo. We used oxygen and glucose deprivation/reoxygenation (OGD/R) in primary cultured cortical neurons and a middle cerebral artery occlusion reperfusion (MCAO/R) rat model to mimic ischemic insult. In this study, GSK-3beta siRNA and inhibitors (SB216763 and LiCl) were used to inhibit GSK-3beta in vitro and in vivo. After inhibiting GSK-3beta, expression of total and nuclear Nrf2, Nrf2-ARE binding activity, and expression of Nrf2/ARE pathway-driven genes HO-1 and NQO-1 increased. Overexpression of GSK-3beta yielded opposite results. These results suggest that GSK-3beta downregulates Nrf2 and the Nrf2/ARE pathway in brain ischemia and reperfusion injury. GSK-3beta may be an endogenous antioxidant relevant protein, and may represent a new therapeutic target in treatment of ischemia and reperfusion injury. PMID- 26838165 TI - On the automaticity of relational stimulus processing. AB - While it is widely accepted that the semantic analysis of a stimulus can take place in an automatic fashion, it is typically assumed that non-automatic processes are required to process the relation of one stimulus relative to other stimuli. Nevertheless, there is evidence to support the idea that such relational stimulus processing can also take place under automaticity conditions. We examined this hypothesis further in four sequential priming experiments in which participants were asked to categorize target objects as larger or smaller than a reference object (i.e., a football or a car). Crucially, some primes were objects that were larger than the small reference object but smaller than the large reference object (e.g., a bike). Results showed that the impact of these primes upon target responding was dependent on the size of the reference object. When the size of the reference object was small, these primes facilitated responses towards large targets relative to small targets. Vice versa, when the size of the reference object was large, the same set of primes facilitated responses towards small targets relative to large targets. This result was obtained when the size of the reference object was manipulated block-wise (Experiments 1 and 3), trial wise (Experiments 2 and 4), and even when the primes were presented near subjective recognition thresholds (Experiment 4). Taken together, our findings provide strong evidence for the hypothesis that complex relational stimulus processing can take place under automaticity conditions. A possible underlying mechanism is proposed. PMID- 26838167 TI - Modalities of Thinking: State and Trait Effects on Cross-Frequency Functional Independent Brain Networks. AB - Functional states of the brain are constituted by the temporally attuned activity of spatially distributed neural networks. Such networks can be identified by independent component analysis (ICA) applied to frequency-dependent source localized EEG data. This methodology allows the identification of networks at high temporal resolution in frequency bands of established location-specific physiological functions. EEG measurements are sensitive to neural activity changes in cortical areas of modality-specific processing. We tested effects of modality-specific processing on functional brain networks. Phasic modality specific processing was induced via tasks (state effects) and tonic processing was assessed via modality-specific person parameters (trait effects). Modality specific person parameters and 64-channel EEG were obtained from 70 male, right handed students. Person parameters were obtained using cognitive style questionnaires, cognitive tests, and thinking modality self-reports. EEG was recorded during four conditions: spatial visualization, object visualization, verbalization, and resting. Twelve cross-frequency networks were extracted from source-localized EEG across six frequency bands using ICA. RMANOVAs, Pearson correlations, and path modelling examined effects of tasks and person parameters on networks. Results identified distinct state- and trait-dependent functional networks. State-dependent networks were characterized by decreased, trait dependent networks by increased alpha activity in sub-regions of modality specific pathways. Pathways of competing modalities showed opposing alpha changes. State- and trait-dependent alpha were associated with inhibitory and automated processing, respectively. Antagonistic alpha modulations in areas of competing modalities likely prevent intruding effects of modality-irrelevant processing. Considerable research suggested alpha modulations related to modality specific states and traits. This study identified the distinct electrophysiological cortical frequency-dependent networks within which they operate. PMID- 26838166 TI - Voluntary eye movements direct attention on the mental number space. AB - Growing evidence suggests that orienting visual attention in space can influence the processing of numerical magnitude, with leftward orienting speeding up the processing of small numbers relative to larger ones and the converse for rightward orienting. The manipulation of eye movements is a convenient way to direct visuospatial attention, but several aspects of the complex relationship between eye movements, attention orienting and number processing remain unexplored. In a previous study, we observed that inducing involuntary, reflexive eye movements by means of optokinetic stimulation affected number processing only when numerical magnitude was task relevant (i.e., during magnitude comparison, but not during parity judgment; Ranzini et al., in J Cogn Psychol 27, 459-470, (2015). Here, we investigated whether processing of task-irrelevant numerical magnitude can be modulated by voluntary eye movements, and whether the type of eye movements (smooth pursuit vs. saccades) would influence this interaction. Participants tracked with their gaze a dot while listening to a digit. The numerical task was to indicate whether the digit was odd or even through non spatial, verbal responses. The dot could move leftward or rightward either continuously, allowing tracking by smooth pursuit eye movements, or in discrete steps across a series of adjacent locations, triggering a sequence of saccades. Both smooth pursuit and saccadic eye movements similarly affected number processing and modulated response times for large numbers as a function of direction of motion. These findings suggest that voluntary eye movements redirect attention in mental number space and highlight that eye movements should play a key factor in the investigation of number-space interactions. PMID- 26838168 TI - Caffeic acid phenethyl ester activates pro-apoptotic and epithelial-mesenchymal transition-related genes in ovarian cancer cells A2780 and A2780cis. AB - Ovarian cancer is a highly aggressive pathology, displaying a poor prognosis and chemoresistance to classical therapy. The present study was conducted to evaluate the effect of caffeic acid phenethyl ester (CAPE) on survival of ovarian cancer cell lines, A2780 (sensitive to cisplatin) and A2780cis (resistant to cisplatin). MTT assay was used to evaluate cell viability, while the apoptotic processes were examined by flow cytometry and qRT-PCR. A reduction of cell proliferation and activation of the apoptosis was observed in both cell lines. qRT-PCR evaluation demonstrated the activation of the pro-apoptotic genes (BAD, CASP8, FAS, FADD, p53) in both cell lines. The limited therapeutic effect in A2780 cells is explained by the activation of epithelial-mesenchymal transition-related genes (ZEB1, ZEB2, or TGFBB1) as displayed by Ingenuity Network analysis. Overall data suggest that CAPE can be used as an alternative in sensitizing cells to chemotherapy. PMID- 26838170 TI - [Medical examination: Preparation for ENT specialisation: Part 23]. PMID- 26838171 TI - Fetal and maternal manifestations of tuberous sclerosis complex: Value of fetal MRI. AB - Tuberous sclerosis complex (TSC) is a genetic disorder characterized by benign hamartomas in various organ systems of the body. Prenatal screening of fetuses of mothers affected with TSC using ultrasonography (US) may detect cardiac lesions. Fetal US is not sensitive for evaluation of the brain. We describe brain MRI findings in a fetus with cardiac rhabdomyomas identified on prenatal screening US. Postnatal brain MRI at 5 days of age demonstrated fetal MRI findings without significant added information. Fetal MRI is the imaging modality of choice for evaluation of cerebral manifestations of TSC. Maternal manifestations of TSC in the abdomen or pelvis may also be demonstrated on fetal MRI. PMID- 26838169 TI - Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism. AB - Kolaviron is a mixture of biflavonoids found in the nut of the West African edible seed Garcinia kola, and it has been reported to exhibit a wide range of pharmacological activities. In this study, we investigated the effects of kolaviron in neuroinflammation. The effects of kolaviron on the expression of nitric oxide/inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2)/cyclooxygenase-2, cellular reactive oxygen species (ROS) and the pro inflammatory cytokines were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Molecular mechanisms of the effects of kolaviron on NF-kappaB and Nrf2/ARE signalling pathways were analysed by immunoblotting, binding assays and reporter assays. RNA interference was used to investigate the role of Nrf2 in the anti-inflammatory effect of kolaviron. Neuroprotective effect of kolaviron was assessed in a BV2 microglia/HT22 hippocampal neuron co-culture. Kolaviron inhibited the protein levels of NO/iNOS, PGE2/COX-2, cellular ROS and the pro inflammatory cytokines (TNFalpha and IL-6) in LPS-stimulated microglia. Further mechanistic studies showed that kolaviron inhibited neuroinflammation by inhibiting IkappaB/NF-kappaB signalling pathway in LPS-activated BV2 microglia. Kolaviron produced antioxidant effect in BV2 microglia by increasing HO-1 via the Nrf2/antioxidant response element pathway. RNAi experiments revealed that Nrf2 is needed for the anti-inflammatory effects of kolaviron. Kolaviron protected HT22 neurons from neuroinflammation-induced toxicity. Kolaviron inhibits neuroinflammation through Nrf2-dependent mechanisms. This compound may therefore be beneficial in neuroinflammation-related neurodegenerative disorders. PMID- 26838172 TI - Hyperintense perilesional edema in the brain on T1-weighted images: Cavernous malformation or metastatic melanoma? Three case reports and literature review. AB - Hyperintense perilesional edema in brain masses on T1-weighted images (T1WI) is an unusual radiological finding. We report three cases showing this particular type of edema, one representing cerebral hemorrhagic cavernous malformation (CCM, cavernoma) and the other two, metastases of melanoma. The association between this sign and cavernoma was recently recognized. On the other hand, in melanotic lesions, the relationship with T1WI-hyperintense perilesional edema has not yet been described. Despite being an infrequent sign, it can considerably narrow the differential diagnosis, which gives it a high value for clinical practice. Moreover, given the high prevalence of the entities that manifest this imaging feature, it can be occasionally noticed. PMID- 26838173 TI - Unique cause of right hemispheric syndrome: Embolism of myocardium after open septal myectomy. AB - We present a novel case of acute ischemic stroke in the postoperative setting of open septal myectomy. A 24-year-old woman developed acute left hemiparesis and rightward eye deviation the morning after surgery. She underwent emergent endovascular stoke therapy by mechanical embolectomy with successful retrieval of a fragment of myocardium that was obstructing the right middle cerebral artery. To our knowledge there has been no previous case described of a myocardial fragment causing a proximal intracranial artery occlusion with resulting ischemia and infarction. PMID- 26838174 TI - Flow-diverter devices in the treatment of intracranial aneurysms: A meta-analysis and systematic review. AB - OBJECTIVE: The purpose of this report was to discuss the overall limitations, safety and efficacy of flow-diverter stenting for intracranial aneurysms. METHODS: The authors performed a meta-analysis from January 2009 to September 2014 using the terms "flow diverter" and "intracranial aneurysms." Additional studies were identified through references in each reviewed article. Data extraction, performed independently by the authors, included demographic data, technical and clinical complications, morbidity and mortality, aneurismal occlusion rates related to flow-diverter devices. The analysis was performed using a fixed effect. RESULTS: Twenty-nine studies with 1524 patients and three to 62 months of follow-up were identified for analysis. The overall technical failure and complication rate was 9.3% (95% CI 6%-12.6%). The rate of procedure related complication was 14% (95% CI 10.2%-17.9%) and 6.6% (95% CI 4%-9.1%) for morbidity and mortality. Fusiform, dissecting and circumferential aneurysm (OR 3.10, 95% CI 0.93-10.37) were significant risk factors for technical failure and complication. Posterior circulation location (OR 4.03, 95% CI 2.45-6.61), peripheral location (OR 2.74, 95% CI 1.52-4.94) and fusiform, dissecting and circumferential aneurysm (OR 1.95, 95% CI 1.15-3.30) were statistically significant risk factors for procedure-related complications. Posterior circulation location (OR 4.39, 95% CI 2.44-7.90) and peripheral location (OR 3.64, 95% CI 1.74-7.62) were statistically significant risk factors for morbidity and mortality. CONCLUSIONS: Fusiform, dissecting and circumferential aneurysm, posterior circulation and peripheral locations have greater procedure-related complications. PMID- 26838176 TI - Two betweenness centrality measures based on Randomized Shortest Paths. AB - This paper introduces two new closely related betweenness centrality measures based on the Randomized Shortest Paths (RSP) framework, which fill a gap between traditional network centrality measures based on shortest paths and more recent methods considering random walks or current flows. The framework defines Boltzmann probability distributions over paths of the network which focus on the shortest paths, but also take into account longer paths depending on an inverse temperature parameter. RSP's have previously proven to be useful in defining distance measures on networks. In this work we study their utility in quantifying the importance of the nodes of a network. The proposed RSP betweenness centralities combine, in an optimal way, the ideas of using the shortest and purely random paths for analysing the roles of network nodes, avoiding issues involving these two paradigms. We present the derivations of these measures and how they can be computed in an efficient way. In addition, we show with real world examples the potential of the RSP betweenness centralities in identifying interesting nodes of a network that more traditional methods might fail to notice. PMID- 26838175 TI - Co-expression of active human cytochrome P450 1A2 and cytochrome P450 reductase on the cell surface of Escherichia coli. AB - BACKGROUND: Human cytochrome P450 (CYP) enzymes mediate the first step in the breakdown of most drugs and are strongly involved in drug-drug interactions, drug clearance and activation of prodrugs. Their biocatalytic behavior is a key parameter during drug development which requires preparative synthesis of CYP related drug metabolites. However, recombinant expression of CYP enzymes is a challenging bottleneck for drug metabolite biosynthesis. Therefore, we developed a novel approach by displaying human cytochrome P450 1A2 (CYP1A2) and cytochrome P450 reductase (CPR) on the surface of Escherichia coli. RESULTS: To present human CYP1A2 and CPR on the surface, we employed autodisplay. Both enzymes were displayed on the surface which was demonstrated by protease and antibody accessibility tests. CPR activity was first confirmed with the protein substrate cytochrome c. Cells co-expressing CYP1A2 and CPR were capable of catalyzing the conversion of the known CYP1A2 substrates 7-ethoxyresorufin, phenacetin and the artificial substrate luciferin-MultiCYP, which would not have been possible without interaction of both enzymes. Biocatalytic activity was strongly influenced by the composition of the growth medium. Addition of 5-aminolevulinic acid was necessary to obtain a fully active whole cell biocatalyst and was superior to the addition of heme. CONCLUSION: We demonstrated that CYP1A2 and CPR can be co-expressed catalytically active on the cell surface of E. coli. It is a promising step towards pharmaceutical applications such as the synthesis of drug metabolites. PMID- 26838178 TI - The discriminatory capability of existing scores to predict advanced colorectal neoplasia: a prospective colonoscopy study of 5,899 screening participants. AB - We evaluated the performance of seven existing risk scoring systems in predicting advanced colorectal neoplasia in an asymptomatic Chinese cohort. We prospectively recruited 5,899 Chinese subjects aged 50-70 years in a colonoscopy screening programme(2008-2014). Scoring systems under evaluation included two scoring tools from the US; one each from Spain, Germany, and Poland; the Korean Colorectal Screening(KCS) scores; and the modified Asia Pacific Colorectal Screening(APCS) scores. The c-statistics, sensitivity, specificity, positive predictive values(PPVs), and negative predictive values(NPVs) of these systems were evaluated. The resources required were estimated based on the Number Needed to Screen(NNS) and the Number Needed to Refer for colonoscopy(NNR). Advanced neoplasia was detected in 364 (6.2%) subjects. The German system referred the least proportion of subjects (11.2%) for colonoscopy, whilst the KCS scoring system referred the highest (27.4%). The c-statistics of all systems ranged from 0.56-0.65, with sensitivities ranging from 0.04-0.44 and specificities from 0.74 0.99. The modified APCS scoring system had the highest c-statistics (0.65, 95% C.I. 0.58-0.72). The NNS (12-19) and NNR (5-10) were similar among the scoring systems. The existing scoring systems have variable capability to predict advanced neoplasia among asymptomatic Chinese subjects, and further external validation should be performed. PMID- 26838179 TI - Induction of heme oxygenase-1 by hemin protects lung against orthotopic autologous liver transplantation-induced acute lung injury in rats. AB - BACKGROUND: Post-liver transplantation acute lung injury (ALI) severely affects patients' survival, whereas the mechanism is unclear and effective therapy is lacking. The authors postulated that reperfusion-induced increased oxidative stress plays a critical role in mediating post-liver transplantation ALI and that induction of heme oxgenase-1 (HO-1), an enzyme with anti-oxidative stress properties, can confer effective protection of lung against ALI. METHODS: Male Sprague-Dawley rats underwent autologous orthotopic liver transplantation (OALT) in the absence or presence of treatments with the selective HO-1 inducer (Hemin) or HO-1 inhibitor (ZnPP). Lung tissues were collected at 8 h after OALT, pathological scores and lung water content were evaluated; survival rate of rats was analyzed; protein expression of HO-1 was determined by western blotting, and nuclear translocation of Nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor(NF)-kappaB p65 were detected by Immunofluorescence staining. The inflammatory cytokines and oxidative indexes of lung tissue were determined. RESULTS: In lungs harvested at the early stage i.e. 8 h after OALT, Hemin treatment significantly increased superoxide dismutase activities, and reduced malondialdehyde, hydrogen peroxide, interleukin-6, myeloperoxidase, and tumor necrosis factor-alpha production,which were associated with increased HO-1 protein expression and lower pathological scores and increased survival rate of rats. The underline mechanisms might associate with activation of Nrf2 and inhibition of NF-kappaB p65 nuclear translocation. However, these changes were aggravated by ZnPP. CONCLUSIONS: Hemin pretreatment, by enhancing HO-1 induction, increased lung antioxidant capacity and reduced inflammatory stress,protected the lung from OALT-induced ALI at early stage of reperfusion. PMID- 26838180 TI - Diapause is associated with a change in the polarity of secretion of insulin-like peptides. AB - The insulin/IGF-1 signalling (IIS) pathway plays an important role in the regulation of larval diapause, the long-lived growth arrest state called dauer arrest, in Caenorhabditis elegans. In this nematode, 40 insulin-like peptides (ILPs) have been identified as putative ligands of the IIS pathway; however, it remains unknown how ILPs modulate larval diapause. Here we show that the secretory polarity of INS-35 and INS-7, which suppress larval diapause, is changed in the intestinal epithelial cells at larval diapause. These ILPs are secreted from the intestine into the body cavity during larval stages. In contrast, they are secreted into the intestinal lumen and degraded during dauer arrest, only to be secreted into the body cavity again when the worms return to developmental growth. The process that determines the secretory polarity of INS 35 and INS-7, thus, has an important role in the modulation of larval diapause. PMID- 26838181 TI - Metal ion transport quantified by ICP-MS in intact cells. AB - The use of ICP-MS to measure metal ion content in biological tissues offers a highly sensitive means to study metal-dependent physiological processes. Here we describe the application of ICP-MS to measure membrane transport of Rb and K ions by the Na,K-ATPase in mouse skeletal muscles and human red blood cells. The ICP MS method provides greater precision and statistical power than possible with conventional tracer flux methods. The method is widely applicable to studies of other metal ion transporters and metal-dependent processes in a range of cell types and conditions. PMID- 26838182 TI - Anti-steatotic and anti-inflammatory roles of syringic acid in high-fat diet induced obese mice. AB - This study examined the effects of syringic acid (SA) on obese diet-induced hepatic dysfunction. Mice were fed high-fat diet (HFD) with or without SA (0.05%, wt/wt) for 16 weeks. SA reduced the body weight, visceral fat mass, serum levels of leptin, TNFalpha, IFNgamma, IL-6 and MCP-1, insulin resistance, hepatic lipid content, droplets and early fibrosis, whereas it elevated the circulation of adiponectin. SA down-regulated lipogenic genes (Cidea, Ppargamma, Srebp-1c, Srebp 2, Hmgcr, Fasn) and inflammatory genes (Tlr4, Myd88, NF-kappaB, Tnfalpha, Il6), whereas it up-regulated fatty acid oxidation genes (Pparalpha, Acsl, Cpt1, Cpt2) in the liver. SA also decreased hepatic lipogenic enzyme activities and elevated fatty acid oxidation enzyme activities relative to the HFD group. These findings suggested that dietary SA possesses anti-obesity, anti-inflammatory and anti steatotic effects via the regulation of lipid metabolic and inflammatory genes. SA is likely to be a new natural therapeutic agent for obesity or non-alcoholic liver disease. PMID- 26838183 TI - Repeated cultivation: non-cell disruption extraction of astaxanthin for Haematococcus pluvialis. AB - The operation of cell disruption is indispensable but cost much in microalgae industry. To be simplified, two different reaction mechanisms await in the cell to respond to moderated or stressed environment. The physical and chemical changes of enzyme and turgor pressure of cell in this conversion play an important role in the enhancement of biomass and metabolites. Repeated turgor pressure (based on the structure and mechanics of cell wall) and converted enzyme system (based on photosynthesis) were used to loosen cell wall and then repeated cultivation of Haematococcus pluvialis for astaxanthin extraction was proposed. There was no significant difference of extraction yield between the broken cell (94.75 +/- 3.13%) and non-broken cell (92.32 +/- 3.24%) treated by the repeated cultivation. Meanwhile, fed-batch culture according to the relationship among pH and nutrient concentration was used to enhance the biomass of Haematococcus pluvialis with the dry cell weight of 1.63 +/- 0.07 g/L. PMID- 26838184 TI - Interaction of the diabetes mellitus and cardiac diseases on survival outcomes in out-of-hospital cardiac arrest. AB - BACKGROUND: Diabetes mellitus (DM) and cardiac disease (CD) both likely effect out-of-hospital cardiac arrest (OHCA) survival, but the effect of their relationship on survival outcomes is unclear. This study aims to investigate whether the association of DM and OHCA outcomes differ in patients with and without CD. METHODS: The study was conducted from the national cardiac arrest registry among OHCA patients who survived to hospital admission from 2009 to 2013. Clinical histories of DM and CD were abstracted from patient medical records. Multivariable logistic regression analysis with an interaction term (DM and CD) was performed to calculate adjusted odds ratios (AORs) for survival to discharge and good cerebral performance category 1 or 2 (good CPC). RESULTS: Among 7583 study-eligible patients, 2651 (34.96%) patients had been previously diagnosed as having DM where 639 (24.1%) diabetic and 753 (15.3%) nondiabetic patients had CD (P<.01). Diabetes mellitus was observed to have harmful effect on survival and good CPC (AORs, 0.84 [0.75-0.95] and 0.81 [0.67-0.97]), whereas CD had nonsignificant effect (AORs, 1.34 [1.17-1.54] and 1.14 [0.94-1.38]). Diabetes mellitus had a significant negative association with survival outcomes in patients with CD (AORs, 0.58 [0.45-0.74] for survival and 0.52 [0.36-0.75] for good CPC), whereas the association was nonsignificant in patients without CD (AORs, 0.93 [0.82-1.06] for survival and [0.76-1.14] for good CPC). CONCLUSION: Diabetes mellitus had a significant negative association with survival to discharge and neurologic recovery among patients with CD, but the association was not significant in patients without CD. PMID- 26838185 TI - Successful therapeutic hypothermia for children surviving near-hanging. PMID- 26838186 TI - The effectiveness of bedside point-of-care ultrasonography in the diagnosis and management of metacarpal fractures: Contribution for management of metacarpal fractures. PMID- 26838188 TI - Epidemiology of injuries sustained by players during the 16th Under-17 South American Soccer Championship. AB - OBJECTIVE: We performed an epidemiological study of the traumatic injuries during the XVI South American U-17 Football Championship, 2015. MATERIAL AND METHODS: Observational surveys submitted by the 10 teams medical services of 220 players. Thirty-five games were held and 116 goals (3.31 per game) were recorded. RESULTS: 103 lesions, ie, 2.94 per game or 32.7 injuries per 1,000 min were recorded. Fifty-six were from direct contact and 66 requiring treatment. 36% of the injuries were punished by fault and 26% of the injuries also saw card. Injuries were most common in the ankle (15 cases), Achilles tendon (14 cases) and thigh (14 cases), followed by trauma to the knee and foot (7 cases each), face and the lumbar region (6 cases each), being rare in the upper extremity. CONCLUSION: Injuries during Soccer World Cup are difficult to predict and prevent, but serious injuries are rare. Is necessary to establish protocols that get adequate health care at all levels to solve problems produce, both in training and during the competition, and be prepared to solve the serious problems that may arise. PMID- 26838189 TI - Aqueous compatible boron nitride nanosheets for high-performance hydrogels. AB - Hexagonal boron nitride nanosheets (BNNSs) possess ultimate thermal and chemical stabilities and mechanical strengths. However, the unmodified BNNSs are hydrophobic and insoluble in water, which hinders their use in many technological areas requiring aqueous compatibility. In this work, h-BN was treated with molten citric acid to produce aqueous dispersible boron nitride sheets (ca-BNNSs). The resultant ca-BNNSs were used to fabricate ca-BNNS/polyacrylamide (i.e., BNNS2.5/PAAm) nanocomposite hydrogels, targeting high water retentivity and flexibility. The BNNS2.5/PAAm hydrogel (initially swollen in water) largely remained swollen (water content ~94 wt%) even after one-year storage under ambient conditions. Importantly, the swollen BNNS2.5/PAAm hydrogel (water content ~95 wt%) was highly flexible. Its elongation and compressive strength exceeded 10,000% and 8 MPa at 97% strain, respectively. Moreover, the aforementioned hydrogel recovered upon the removal of compression force, without obvious damage. The substantially improved water retentivity and flexibility revealed that BNNSs can serve as a promising new platform in the development of high-performance hydrogels. PMID- 26838187 TI - Agreement of serum potassium measured by blood gas and biochemistry analyzer in patients with moderate to severe hyperkalemia. AB - PURPOSE: Several studies investigated the agreement between central laboratory biochemistry analyzers and blood gas analyzers for potassium measurements. However, data are scarce when the potassium level is moderate to severely high. We aimed to evaluate the agreement between central laboratory biochemistry analyzers and blood gas analyzer in terms of serum potassium level measurement because differences in potassium at this level translate into very different clinical actions. BASIC PROCEDURES: This was a retrospective medical record review study in which patients who presented to the emergency department and had serum potassium levels >=6mmol/L were included. Patients who did not have simultaneous potassium measurement by blood gas analyzer were excluded. We included all patients meeting potassium criteria irrespective of their underlying disease or comorbidities. We evaluated agreement between the measurement methods with Pearson correlation, Bland-Altman plot, and Sign test. MAIN FINDINGS: A total of 118 blood sample pairs were included. The mean serum potassium level measured by biochemistry analyzer was 6.78+/-0.79mmol/L, whereas it was 6.16+/ 0.86mmol/L by blood gas analyzer (P<.001, Sign test). There was a strong correlation (P<.001, r=0.864) between the 2 methods, but agreement was relatively poor. Blood gas analyzer tended to measure potassium significantly lower than measured by biochemistry analyzer. The mean difference between the methods was 0.62+/-0.43mmol/L. PRINCIPAL CONCLUSIONS: In patients with moderate to severe hyperkalemia, blood gas analyzer and biochemistry analyzer gives significantly different serum potassium results which may be clinically important. PMID- 26838190 TI - 2-Deoxy-d-Glucose (2-DG)-Induced Cardiac Toxicity in Rat: NT-proBNP and BNP as Potential Early Cardiac Safety Biomarkers. AB - 2-Deoxy-d-glucose (2-DG) is being developed as a potential anticonvulsant and disease-modifying agent for patients with epilepsy; however, during preclinical development, cardiac toxicity has been encountered in rats. This study was performed to determine whether cardiac troponin (cTnI and cTnT), atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and/or creatine kinase (CK) could be useful as indicators of 2-DG cardiac toxicity. In addition, this study also investigated the association of cardiac histopathological changes with these biomarkers. F344 rats (4/sex/group/sacrifice point) were gavaged with either vehicle or 2-DG (50, 125, or 375 mg/kg twice daily; total daily dose of 100, 250, or 750 mg/kg/d) for 7, 14, 21, or 45 days followed by a 15-day recovery. Dose-dependent increases in NT-proBNP and BNP plasma concentrations were observed. Following recovery period, the NT-proBNP and BNP concentrations returned to baseline levels. There were no remarkable increases in CK, ANP, cTnI, or cTnT concentrations. There were no gross cardiac lesions observed at the necropsy. Microscopic findings of vacuolar degeneration and hypertrophy of the endothelial cells of the endocardium were present in the heart at doses of 250 and 750 mg/kg/d. Microscopic findings, in general, were associated with increases in NT-proBNP levels. Cardiac toxicity appeared to be reversible. In conclusion, NT-proBNP and BNP are potential early biomarkers for 2-DG-induced cardiac toxicity that can be useful to monitor 2-DG therapy in clinical trials. PMID- 26838191 TI - In Search for a Common Pathway for Health Issues in Men--the Sign of a Holmesian Deduction. AB - The evidence for the existence of a common pathway for health issues in men is presented in this review. Several epidemiological studies have shown that conditions like cardiovascular diseases (CVD), metabolic syndrome, diabetes, lower urinary tract symptom (LUTS), erectile dysfunction (ED), prostate cancer, hypogonadism, depression and suicide can be associated as risk factors for each other. Thus, the risk of CVD is significantly increased in men with metabolic syndrome, ED, hypogonadism, prostate cancer and/or LUTS. In addition, the above mentioned conditions are more prevalent in atherosclerotic patients. In addition, growing evidence indicates that low androgen levels can cause metabolic syndrome. In addition, obesity, dyslipidaemia and diabetes can further reduce androgen levels potentiating their adverse effect. Low testosterone levels are also associated with a higher incidence of aggressive prostate cancer on biopsy and on definitive pathology, and lower probability of abiraterone response in the metastatic setting. Several recent studies point towards diffuse endothelial dysfunction and dysregulated pro-inflammatory state as the biological link between all these disorders. Our current hypothesis is that oxidative stress caused by these dysfunctions explains the pathogenesis of each of these conditions. PMID- 26838193 TI - Diabetes is an Important Risk Factor for Metastasis in Non- Muscle-Invasive Bladder Cancer. AB - BACKGROUND: Epidemiological evidence indicates that individuals with diabetes mellitus (DM) may have a modestly increased risk of bladder cancer. In the present study, we aimed to show any association between DM and risk of metastasis in patients with non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: We retrospectively analyzed 698 patients between January 2007 and December 2014 who were diagnosed with and underwent transurethral resection of bladder tumors (TUR-BT). Comparisons of means was conducted by independent samples t test, and relations between categorical variables were investigated by non-parametric chi- square test. A p value of 0.05 was accepted as statistically significant in comparisons. RESULTS: We analyzed 418 patients with non muscle invasive bladder cancer. 123 of whom were diabetic and 295 non-diabetic. In diabetic patients, 13 were N1 stage and 11 M1 stage. When compared with non diabetic patients that was statistically significant (p<0.001). TNM stages were more advanced in diabetic patients (p<0.001), but concurrent CIS (p=0.1) and squamous metaplasia did not significantly differ between diabetic and non diabetic cases (p=1). CONCLUSIONS: Diabetic patients with non-muscle-invasive bladder cancer may suffer metastases earlier than expected although they are non invasive. Therefore such patients must be followed-up carefully and early cystectomy decision may be necessary. Further prospective studies with more patients are needed to confirm these findings. PMID- 26838192 TI - Treating Adults with Hodgkin Lymphoma in the Developing World: a Hospital-Based Cohort Study from Armenia. AB - BACKGROUND: With advances in diagnostics and treatment approaches, patients with Hodgkin's lymphoma (HL) in developed countries can nowadays expect to have excellent outcomes. However, information about the characteristics and outcomes in the developing world is very scarce, and this is important given the fact that there are several reports about differences of disease characteristics depending on geographic location and the development level of the country. MATERIALS AND METHODS: In this retrospective study we assessed the features of 36 adult (>=18 years old) patients with HL and their diagnosis and treatment and outcomes in the Clinic of Chemotherapy of Muratsan University Hospital of Yerevan State Medical University, Armenia, between 2008- 2014. RESULTS: All patients had classic HL and among them 19 (53%) had nodular sclerosis subtype, 8 (22%) mixed cellularity and 9 (25%) lymphocyte-rich. 16 (44.5%) patients were at stage II, 13 (36%) stage III and 7 (19.5%) stage IV. Median follow-up time was 24.5 months (range 1-71 months) and during the whole follow- up period only two relapses (early) were documented and there were no deaths. Twenty-three (64%) patients received a BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) regimen, and 13 (36%) ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) regimen. A total of 25 (69.5%) patients received radiation in addition to chemotherapy. CONCLUSIONS: Although the number of patients involved in the study is small and the median follow-up time was just two years, this retrospective study shows that treatment of HL can be successfully organized in a resource-limited setting. PMID- 26838194 TI - Are p53 Antibodies a Diagnostic Indicator for Patients with Oral Squamous Cell Carcinoma? Systematic Review and Meta-Analysis. AB - BACKGROUND: P53 has been reported to be involved with tumorigenesis and has also been implicated as a significant biomarker in oral squamous cell carcinoma(OSCC). However, the diagnostic value of p53 antibodies remains controversial; hence, we comprehensively and quantitatively assessed the potential in the present systematic review. MATERIALS AND METHODS: A comprehensive search was performed using PubMed and Embase, up to October 31, 2014, without language restriction. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures using diagnostic odds ratios (DORs) and symmetric summary receiver operating characteristic (SROC) curves. RESULTS: Of 150 studies initially identified, 7 eligible regarding serum p53 antibodies met the inclusion criteria. Some 85.7% (6/7) were of relatively high quality (QUADAS score>=7). The summary estimates for quantitative analysis of serum p53 antibody in the diagnosis of squamous cell carcinoma were: PLR 2.06 [95% confidence interval (CI) : 1.35-3.15], NLR 0.85 (95%CI: 0.80- 0.90) and DOR 2.47 (95%CI: 1.49- 4.12). CONCLUSIONS: This meta analysis suggests that the use of s-p53-antibodies has potential diagnostic value with relatively high sensitivity and specificity for OSCC particularly with serum specimens for discrimination of OSCCs from healthy controls. However, its discrimination power is not perfect because of low sensitivity. PMID- 26838195 TI - Combination between Taxol-Encapsulated Liposomes and Eruca sativa Seed Extract Suppresses Mammary Tumors in Female Rats Induced by 7,12 Dimethylbenz(alpha)anthracene. AB - Taxol (paclitaxel) is a powerful anti-cancer drug widely used against several types of malignant tumors. Because Taxol may exert several side effects, a variety of formulations have been developed. One of these features liposomes, regarded as one of the most promising drug carriers, biocompatible and best able to reduce drug toxicity without changing efficacy against tumor cells. Eruca sativa seed extract (SE) is considered a promising natural product from cruciferous vegetables against breast cancer, increasing chemotherapeutic and eliminating harmful side effects. The effects of Taxol-encapsulated liposomes (T) alone and in combination between Eruca sativa seed extract on nuclear factor kappa B (NF-kappaB), cyclooxygenase-2 (COX-2) and B-cell lymphoma-2 (Bcl-2) gene expression levels were investigated in rat mammary gland carcinogenesis induced by 7,12 dimethylbenz(alpha) anthracene (DMBA) using qRT-PCR. The results showed that DMBA increased NF-kappaB, COX-2 and Bcl-2 gene expression levels and lipid peroxidation (LP), while decreasing glutathione-S-transferase (GST) and superoxide dismutase (SOD) activities and total antioxidant concentration (TAC) compared to the control group. T and T-SE treatment reduced NF-kappaB, COX-2 and Bcl-2 gene expression levels and LP. Hence, T and T-SE treatment appeared to reduce inflammation and cell proliferation, while increasing apoptosis, GST and SOD activities and TAC. PMID- 26838197 TI - Effect of First Line Gastric Cancer Chemotherapy Regime on the AGS Cell Line - MTT Assay Results. AB - BACKGROUND: Combination chemotherapy regimes are common treatments for cancer. The aim of this study was to evaluation the effect of individual chemotherapeutic agents in comparison with a first line chemotherapy regime treatment in the AGS gastric cancer cell line by MTT assay. MATERIALS AND METHODS: In this experimental study, AGS cells were grown in RPMI-1640 supplemented with 10% fetal calf serum and 100 IU/ml penicillin, and 10 MUg/ml streptomycinin, under a humidified condition at 37 degrees with 5% CO2. All cells were washed with PBS and detached with trypsin, centrifuged and 8000 cells re-plated on to 96- well plates. LD50 doses of Epirubicin, Cisplatin and 5-fluorouracil were added to each well in mono or triple therapy. Anti-proliferative activities were determined by MTT assay after 24, 48 or 72 h. RESULTS: Results of MTT assays showed that there were no significant differences among 3 drugs in monotherapy (p=0.088), but there was significant difference between combination therapy with epirubicin (P=0.031) and 5FU (p=0.013) on cell survival at 24 h. After 48 and 72 hours, cell viability showed significant differences between the 3 drugs (p=0.048 and P=0.000 for 48 and 72 h, respectively) and there was significant difference between combination therapy with epirubicin (P=0.035 and P=0.002 for 48 and 72 h, respectively). CONCLUSIONS: The results showed no significant differences between these chemotherapy drugs each given alone, but combination therapy with 3 drugs had significant effects on cell viability in comparison with epirubicin alone. PMID- 26838196 TI - Factors Predicting Early Release of Thyroid Cancer Patients from the Isolation Room after Radioiodine-131 Treatment. AB - BACKGROUND: Patients with differentiated thyroid cancers (DTC) who receive radioactive iodine-131 (RAI) are released from isolation when their dose rate is below the regulatory requirements. The purpose of this study was establish predicting factors for early release from the isolation facility after RAI administration in patients with DTC. MATERIALS AND METHODS: This was a prospective study which included 96 (58 females and 38 males) patients with DTC who had received RAI from April 2013 till August 2015. The study was duly approved by the ethical committee of the institute. Patients who had complete information of primary tumor size (PTS), serum TSH, stimulated thyroglobulin level [sTg] with antibodies (IU/ml) at the time of RAI treatment were included. All had a normal serum creatinine level. To attain lower effective half-life good hydration and administration of soft laxative were ensured. Dose rate was measured (immediately, 24 h and 36 h) at 1 meter distance from anterior mid trunk and a dose rate <50 MUSv/h was considered as the releasing criterion. At 24 h 50 patients were released while the remaining 46 patients were released at 36 h. A post-ablative whole body scan (PA-WBIS) was performed 5-8 days after RAI ablation in all patients. RESULTS: Patients released after 24 h were significantly younger, had smaller lesions with higher proportion of papillary cancer, lower sTg, lower sTg/TSH ratio and had received a lower dose of RAI as comapred to those who were discharged after 36 h. Serum TSH and gender were not found to have any significant correlation between two cohorts. ROC and multivariate analysis have shown age <=37 years, PTS <= 3.8 cm, RAI <= 150 mCi, sTg <= 145 ng/ml and sTg/TSH <= 1.085 as strong indepedent predictors for early release. CONCLUSIONS: We conclude that younger age (<=37 years), smaller tumor size (<=3.8 cm), lower RAI dose (<=150 mCi), lower sTg (<=145 ng/ml) and a lower sTg/TSH ratio (<= 1.085) are significant independent predictors for release at 24 h after RAI treatment in DTC patients. Effective utilization of these factors could help the treating physicians to use limited number of internment facilities with higher throughput, lower cost and lower psychological stress to patients. PMID- 26838198 TI - High-grade Cervical Histopathology in Women with Atypical Glandular Cell Cytology. AB - This study was undertaken to evaluate the prevalence of underlying significant lesions among women referred for colposcopy after atypical glandular cell (AGC) smears and the associated risks. The present study reviewed data from women with AGC smears undergoing colposcopy at the Colposcopy Clinic, Faculty of Medicine, Khon Kaen University, Thailand between January 2001 to December 2014. Significant lesions included cervical intraepithelial neoplasia grade 2-3, adenocarcinoma in situ, endometrial hyperplasia, and cancer. During the study period, 170 women with AGC cytology were reviewed. The mean age was 45.7 years. Thirty-eight women (22.4%) were postmenopausal. Eighteen smears (10.6%) were further subclassified as AGC-favor neoplasia (AGC-FN). In total, significant lesions were noted in 27 women (15.9%; 95%CI, 7.8%-18.3%). Thirteen women (7.6%, 95%CI, 4.1%-12.7%) were found to have cervical cancer or endometrial cancer. Two variables were independently associated with an increased risk of significant histopathology results: level of educational attainment (secondary level or lower versus bachelor degree or higher) and types of AGC (AGC versus AGC- FN). Women who had low level of education and those with AGC-FN were at the higher risk of significant lesions (OR, 3.16; 95%CI 1.10-9.11 and OR, 4.62; 95%CI, 1.54-13.85, respectively). In conclusion, the rate of significant lesions among women referred for colposcopy after AGC smears is considerably high. Low education and smear subtypes appear independently associated with a higher risk of significant lesions. PMID- 26838199 TI - The Relation between Exposure to Environmental Tobacco Smoke and the Quantity of Cotinine in the Urine of School Children in Taif City, Saudi Arabia. AB - Environmental tobacco smoke (ETS) is a major public health problem for all ages. Despite the high prevalence of smoking among the Saudi population, there is limited information about levels of urinary cotinine in Saudi children exposed to SHS. The aim of the study was to assess the exposure of schoolchildren to ETS, and measure their urinary cotinine levels. Multistage cluster sampling was carried out, where schoolchildren from 4 schools were randomly chosen from primary schools in Taif city. A questionnaire including questions on SHS exposure and smoking rules in the residence were sent to students parents/guardians. Urine samples were taken and analyzed for total cotinine using chemiluminescent immunoassay. Of the studied children, 38.4% had a smoking father, 61.8%, 41.2% and 49.3% of them were exposed to ETS indoors, outdoors and both indoors and outdoors respectively. The mean urinary cotinine was significantly higher among children exposed to ETS compared to unexposed children. Urinary cotinine levels in children with both indoor and outdoor exposure was significantly higher compared with its level in children with single exposure. A significant positive correlation was found between urinary cotinine concentrations and the number of cigarette packs smoked by parents, and the number of smokers in the residence. The mean urinary cotinine level was significantly higher in children who reported no smoking rules at the residence.. The study revealed a high exposure of Saudi children to ETS. An antismoking media awareness campaign on the harmful effects of ETS should be carried out, in addition to family counseling programs targeted to parents to protect their children from ETS. PMID- 26838200 TI - Immunohistochemical Evaluation of Glucose Transporter Type 1 in Epithelial Dysplasia and Oral Squamous Cell Carcinoma. AB - Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and some of these have been documented in association or preceded by oral epithelial dysplasia (OED). Aggressive cancers with fast growth have demonstrated overexpression of some glucose transporters (GLUTs). Thus, the aim of this study was to analyze the immunohistochemical expression of the glucose transporter, GLUT-1, in OEDs and OSCCs, seeking to better elucidate the biological behavior of neoplasias. Fifteen cases were selected this research of both lesions. Five areas were analyzed from each case by counting the percentage of positive cells at 400x magnification. Immunoreactivity of GLUT-1 was observed in 100% of the samples ranging from 54.2% to 86.2% for the OSCC and 73.9% to 97.4% for the OED. Statistical test revealed that there was greater overexpression of GLUT-1 in OED than the OSCC (p=0.01). It is believed the high expression of GLUT-1 may reflect the involvement of GLUT-1 in early stages of oral carcinogenesis. PMID- 26838201 TI - Polycyclic Aromatic Hydrocarbons (PAHs) and their Bioaccessibility in Meat: a Tool for Assessing Human Cancer Risk. AB - Polycyclic aromatic hydrocarbons (PAHs) are primarily formed as a result of thermal treatment of food, especially barbecuing or grilling. Contamination by PAHs is due to generation by direct pyrolysis of food nutrients and deposition from smoke produced through incomplete combustion of thermal agents. PAHs are ubiquitous compounds, well-known to be carcinogenic, which can reach the food in different ways. As an important human exposure pathway of contaminants, dietary intake of PAHs is of increasing concern for assessing cancer risk in the human body. In addition, the risks associated with consumption of barbecued meat may increase if consumers use cooking practices that enhance the concentrations of contaminants and their bioaccessibility. Since total PAHs always overestimate the actual amount that is available for absorption by the body, bioaccessibility of PAHs is to be preferred. Bioaccessibility of PAHs in food is the fraction of PAHs mobilized from food matrices during gastrointestinal digestion. An in vitro human digestion model was chosen for assessing the bioaccessibility of PAHs in food as it offers a simple, rapid, low cost alternative to human and animal studies; providing insights which may not be achievable in in vivo studies. Thus, this review aimed not only to provide an overview of general aspects of PAHs such as the formation, carcinogenicity, sources, occurrence, and factors affecting PAH concentrations, but also to enhance understanding of bioaccessibility assessment using an in vitro digestion model. PMID- 26838202 TI - Analytical Consideration of Surface Dose and Kerma for Megavoltage Photon Beams in Clinical Radiation Therapy. AB - BACKGROUND: In radiation therapy, estimation of surface doses is clinically important. This study aimed to obtain an analytical relationship to determine the skin surface dose, kerma and the depth of maximum dose, with energies of 6 and 18 megavoltage (MV). MATERIALS AND METHODS: To obtain the dose on the surface of skin, using the relationship between dose and kerma and solving differential equations governing the two quantities, a general relationship of dose changes relative to the depth was obtained. By dosimetry all the standard square fields of 5x5cm to 40x40cm, an equation similar to response to differential equations of the dose and kerma were fitted on the measurements for any field size and energy. Applying two conditions: a) equality of the area under dose distribution and kerma changes in versus depth in 6 and 18 MV, b) equality of the kerma and dose at x=dmax and using these results, coefficients of the obtained analytical relationship were determined. By putting the depth of zero in the relation, amount of PDD and kerma on the surface of the skin, could be obtained. RESULTS: Using the MATLAB software, an exponential binomial function with R-Square >0.9953 was determined for any field size and depth in two energy modes 6 and 18MV, the surface PDD and kerma was obtained and both of them increase due to the increase of the field, but they reduce due to increased energy and from the obtained relation, depth of maximum dose can be determined. CONCLUSIONS: Using this analytical formula, one can find the skin surface dose, kerma and thickness of the buildup region. PMID- 26838203 TI - Factors Affecting Survival in Patients with Colorectal Cancer in Shiraz, Iran. AB - BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the world, and the fourth in Iran in both genders. The aim of this study was to find predictive factors for CRC survival. MATERIALS AND METHODS: Medical records of 570 patients referred to the radiotherapy oncology department of Shiraz Namazi hospital from 2005 to 2010 were retrospectively analysed. Data were collected by reviewing medical records, and by telephone interviews with patients. Survival analysis was performed using the Cox's regression model with survival probability estimated with Kaplan-Meier curve. The log-rank test was used to compare survival between strata. Data was analyzed with Stata 12. RESULTS: The five-year survival rate and the mean survival time after cancer diagnosis were 58.5% and 67+/-1.4 months. On multivariate analysis, age of diagnosis, disease stage and primary tumor site, lymphovascular invasion and type of treatment (in colon cancer) were significant factors for survival. CONCLUSIONS: Age of diagnosis and type of treatment (adjuvant therapy in patients with colon cancer) were two modifiable factors related to survival of CRC patients. Therefore earlier diagnosis might help increase survival. PMID- 26838204 TI - Factors Predicting Nurse Intent and Status Regarding Pap Smear Examination in Taiwan: a Cross-sectional Survey. AB - BACKGROUND: Nurses are the most visible, frontline personnel providing health education to patients. In particular, nurse experience with Pap examinations have the potential to influence women's attitudes toward screening for cervical cancer. However, nurses in Taiwan have lower rates of Pap testing than the general population. Understanding the factors predicting nurse intent to have a Pap exam and Pap exam status would inform interventions and policies to increase their Pap exam uptake. Therefore, the present study was undertaken. MATERIALS AND METHODS: Data were collected by questionnaire from a convenient sample of 504 nurses at a regional hospital in central Taiwan between August and October 2011 and analyzed by descriptive statistics, confirmatory factor analysis, and logistic regression. RESULTS: Nurse intention to have a Pap exam was predicted by younger age, less negative attitudes toward Pap exams, and greater influence of others recommendations. However, nurses were more likely to actually have had a Pap exam if they were older, married, had sexual experience, and had a high intention to have a Pap exam. CONCLUSIONS: Nurses who are younger than 34 years old, unmarried, sexually inexperienced, and with low intention to have a Pap exam should be targeted with interventions to educate them not only about the importance of Pap exams in detecting cervical cancer, but also about strategies to decrease pain and embarrassment during exams. Nurses with less negative attitudes and experiences related to Pap exams would serve as role models to persuade women to have Pap exams, thus increasing the uptake rate of Pap exams in Taiwan. PMID- 26838205 TI - Symptom Prevalence and Related Distress in Cancer Patients Undergoing Chemotherapy. AB - BACKGROUND: Much has been done to examine the psychological impact of cancer treatment, but it remains unclear to what extent anxiety and depression is related to symptom prevalence. The present study concerned the characteristics and frequency of distress as related to symptom prevalence in cancer patients undergoing chemotherapy in Malaysia. MATERIALS AND METHODS: Participants were 303 consecutive adult cancer patients undergoing chemotherapy in an academic medical center. The short form Memorial Symptom Assessment Scale (MSAS-SF), which covers three domains of symptoms (global distress, physical- and psychological symptoms) was used to cross-sectionally measure symptom frequency and associated distress via self-reporting. One-way ANOVA and t-tests were used to test mean differences among MSAS-SF subscale scores. RESULTS: Complete data were available for 303 patients. The mean number of symptoms was 14.5. The five most prevalent were fatigue, dry mouth, hair loss, drowsiness and lack of appetite. Overall, symptom burden and frequency were higher than in other published MSAS-SF studies. Higher symptom frequency was also found to be significantly related to greater distress in cancer patients undergoing chemotherapy. CONCLUSIONS: Patients undergoing chemotherapy suffer from multiple physical and psychological symptoms. Better symptom control or palliative care is needed. Greater frequency of reported symptoms may also indicate a subconscious bid by patients for care and reassurance - thus tailored intervention to manage distress should be offered. PMID- 26838206 TI - People Participation Towards Opisthorchis viverrini Prevention and Control in Chaiyaphum Province, Northeastern Thailand. AB - This cross-sectional descriptive and qualitative study was aimed to study the people participation and their approaches toward the human carcinogenic liver fluke, Opisthorchis viverrini, prevention and control in Ban Chaun sub-district administrative organization (BCSAO) and Bamnet Narong sub-district municipality (BNSM), Bamnet Narong district, Chaiyaphum Province, Thailand between June 2013 and February 2014. Participants were purposive selected, included chiefs of sub district administrative organizations, sub-district municipalities, sub-district health promotion hospitals (SHPHs), heads of village, and a further sample was selected with a multi- stage random sampling for public health volunteers, and villagers. The pre-designed questionnaire contained items for individualized status and the participatory steps of sharing ideas, decision-making, and planning, procession, evaluation, and mutual benefit, for the project O. viverrini prevention and control (POPC). In-depth interviews were used for collection of need approaches to POPC. With 375 participants who completed the questionnaire, it was found that people had a high level regarding to participate in the POPC, particularly in the process stage (X_ =3.78, S.D. = 0.56), but the lowest level was found in sharing ideas, decision making, and planning step (X_ =3.65, S.D. = 0.63). By comparison, participant status and organization did not significantly differ with people participation. In each step, Ban Chaun sub district had a high level of participation in the step of sharing ideas, decision making, and planning toward POPC, more than Bamnet Narong sub-district municipality (t=2.20, p=0.028). Approaches for POPC in Ban Chaun sub-district and Bamnet Narong sub-district municipality included requirements for budget support, annual campaigns for liver fluke prevention and control, campaign promotion, risk group observation, home visiting, community rules regarding reducing raw fish consumption in their communities, and a professional public health officer for working in their communities, BCSAO, BNSM, and SHPH, for O. viverrini prevention and control. This study indicates that people realize that eradication of the liver fluke needs a continuous people participation for O. viverrini prevention and control in their communities. PMID- 26838207 TI - Anti-Proliferative Activity and Apoptosis Induction of an Ethanolic Extract of Boesenbergia pandurata (Roxb.) Schlecht. against HeLa and Vero Cell Lines. AB - Rhizomes of Boesenbergia pandurata (Roxb.) Schlecht have been reported to contain active compounds with anticancer properties. This research was carried out to examine anti-proliferative and apoptotic induction against HeLa and Vero cells line. Dried powder of B. pandurata rhizomes was extracted by a maceration method using 90% ethanol. Cytotoxic assays to determine IC50 and anti-proliferative effects were carried out by MTT methods. Observation of apoptosis was achieved with double staining using acridine orange and ethidium bromide. The results showed that ethanolic extract of B. pandurata was more cytotoxic against HeLa cells (IC50 of 60 MUg/ mL) than Vero cells (IC50 of 125 MUg/mL). The extract had higher anti-proliferative activity as well as apoptotic induction in HeLa than Vero cells. Therefore, it was concluded that the ethanolic extract of B. pandurata had anti-proliferative as well as apoptosis induction activity dependent on the cell type. PMID- 26838208 TI - p53 Expression Helps Identify High Risk Oral Tongue Pre- malignant Lesions and Correlates with Patterns of Invasive Tumour Front and Tumour Depth in Oral Tongue Squamous Cell Carcinoma Cases. AB - Oral tongue squamous cell carcinoma (OTSCC) is the most common oral cancer subtype with a maximum propensity for regional spread. Our objective was to study if p53 expression might have any correlation with aggressive patterns of invasion within oral tongue cancers as well as with the histologically identified degree of oral tongue dysplasia. p53 immunoexpression was studied using immunohistochemistry in early staged OTSCCs (n=155), oral tongue dysplasias, (n=29) and oral tongue normal specimens (n=10) and evaluated for correlations with histological and clinicopathological parameters. Our study (n=194) showed a pattern of p53 expression increasing with different grades of tongue dysplasia to different grades of invasive OTSCC (p=0.000). Among the OTSCC tumours, positive p53 expression was seen in 43.2% (67/155) and a higher p53 labelling index was significantly associated with increased Bryne's grade of the tumour invasive front (p=0.039) and increased tumour depth (p=0.018). Among the OTSCC patients with tobacco habits, (n=91), a higher p53 labelling index was significantly associated with increased risk of local recurrence (p=0.025) and with lymphovascular space involvement (p=0.014). Evaluation of p53 through varying degrees of dysplasia to oral tongue cancer indicates that p53 expression is linked to aggressive features of oral tongue cancers and tongue precancers entailing a closer monitoring in positive cases. Among the OTSCCs, p53 expression is associated with tumour aggressiveness correlating with increased grading of invasive tumour front and tumour depth. PMID- 26838209 TI - Determination of an Effective Wedge Angle by Combination of Two Arbitrary Universal Wedge Fields in Radiation Therapy of Cancer Patients with Megavoltage Photon Beams. AB - BACKGROUND: Wedge filters are commonly used in radiation oncology for eliminating hot spots and creating a uniform dose distribution in optimizing isodose curves in the target volume for clinical aspects. These are some limited standard physical wedges (15 degrees , 30 degrees , 45 degrees , 60 degrees ),or creating an arbitrary wedge angle, like motorized wedge or dynamic wedge,... The new formulation is presented by the combination of wedge fields for determining an arbitrary effective wedge angles. The isodose curves also are derived for these wedges. MATERIALS AND METHODS: we performed the dosimetry of Varian Clinac 2100C/D with Scanditronix Wellhofer water blue phantom, CU500E, OmniPro - Accept software and 0.13cc ionization chamber for 6Mv photon beam in depth of 10cm (reference depth) for universal physical wedges (15 degrees , 30 degrees , 45 degrees , and 60 degrees ) and reference field 10x10cm2. By combining the isodose curve standard wedge fields with compatible weighting dose for each field, the effective isodose curve is calculated for any wedge angle. RESULTS: The relation between a given effective wedge angle and the weighting of each combining wedge fields was derived. A good agreement was found between the measured and calculated wedge angles and the maximum deviation did not exceed 3 degrees . The difference between the measured and calculated data decreased when the combined wedge angles were closer. The results are in agreement with the motorized single wedge appliance in the literature. CONCLUSIONS: This technique showed that the effective wedge angle that is obtained from this method is adequate for clinical applications and the motorized wedge formalism is a special case of this consideration. PMID- 26838211 TI - Suitability of a Group Behavioural Therapy Module for Workplace Smoking Cessation Programs in Malaysia: a Pilot Study. AB - In Malaysia, data on components suitability the established smoking cessation module is limited. This exploratory study aimed to evaluate the suitability of the components developed in the module for group behavioural therapy in workplace smoking cessation programs. Twenty staff were identified but only eight individuals were selected according to the study criteria during the recruitment period in May 2014. Focus group discussion was conducted to identify themes relevant to the behavioural issues among smokers. Thematic analysis yielded seven major themes which were reasons for regular smoking, reasons for quitting, comprehending smoking characteristics, quit attempt experiences, support and encouragement, learning new skills and behaviour, and preparing for lapse/relapse or difficult situations. As a result, the developed module was found to be relevant and suitable for use based on these themes. PMID- 26838210 TI - Clinicopathological Significance of Osteopontin in Cholangiocarcinoma Cases. AB - Cholangiocarcinoma (CCA) is generally a rare primary liver tumor of the bile duct with extremely poor clinical outcomes due to late diagnosis. Osteopontin (OPN) is the most abundant expressed gene in intrahepatic CCA and its involvement in tumor aggressiveness suggests it could be a useful prognostic biomarker. However, the prognostic significance of OPN expression in CCA is still controversial. We therefore immunohistochemically studied OPN expression in 354 resected CCAs and correlated the results with patient clinicopathological parameters. OPN expression was separately scored according to the percentage of cancer cells or degree of stromal tissue staining and classified as low (score 0-1) and high (score 2-3). OPN expression in CCA cells was found in 177 out of 354 patients (56.5%), whereas stroma was positive in 185 out of 354 patients (52.3%). Univariate analysis with several of the aforementioned parameters revealed that stromal but not cancer cell OPN expression was significantly associated with tumor size, tumor direct invasion into normal liver parenchyma, regional lymph node metastasis and higher staging. The combination of cancer cell and stromal OPN expression demonstrated a positive trend for linkage with lymph node metastasis. Multivariate analysis identified gender, the presence of lymphatic permeation and lymph node metastasis, but not OPN expression, as independent prognostic factors. This study confirms the presence of stromal OPN expression in tumor aggressiveness but not survival in CCA patients. PMID- 26838212 TI - Watch and Wait in Lebanese Chronic Lymphocytic Leukemia Patients: How Relevant is it? AB - BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most frequent form of leukemia in Europe and North America, and it mainly affects older individuals. Many approaches are implemented in the management of CLL from a watch and wait (WandW) strategy to chemotherapeutic regimens. We here reviewed our clinical practice for the relevance of the W and W strategy in Lebanese CLL patients. MATERIALS AND METHODS: A total of 95 patients with CLL diagnosed in four institutions in Lebanon, between 1992 and 2013, were selected and their files were reviewed. Characteristics of these patients were noted including age, sex, RAI and Binet scores, CBC values, presence of hepatomegaly or splenomegaly, performance of bone marrow biopsy or peripheral blood flux cytometry for diagnosis, adoption of W and W strategy, different chemotherapeutic regimens and the indications for treatment. RESULTS: Some 38 patients (40%) diagnosed with CLL were women and 57 (60%) were men with a mean age of 65.1 years [36-89]. Of the total, 50.5%, 17.2%, 14%, 7.5% and 10.8% had an RAI score at diagnosis of 0, 1, 2, 3 and 4, respectively, while 65.6%, 17.2% and 17.2% had Binet scores of I, II and III. The mean lymphocyte count at diagnosis was 39885/mm3 [1596-290000], the mean hemoglobin level was 12.7 g/dl [6.2-17] and the mean platelet count was 191255/mm3 [14000-458000]. While 26.3% of patients with CLL had splenomegaly, only 7.4% had hepatomegaly. Some 33.7% had undergone a bone marrow biopsy, 66.3% flow cytometry of circulating blood and 5.3% a lymph node biopsy. Overall, the W and W was adopted in 62.4% (58) of patients with a mean duration of 37.7 months [3-216]. The W and W was used in 82.6%, 73.3%, 46.2%, 14.3% and 0% of patients having RAI scores of 0, 1, 2, 3 and 4, respectively, and, it was used in 80%, 46.7% and 6.25% with Binet scores of I, II and III. The most frequent indication for treatment was anemia and thrombocytopenia, accounting for 32.7% of cases. The most frequently used chemotherapeutical regimens were chlorambucil until the end of the last century and flufarabine-cyclophosphamide-rituximab during the last decade. CONCLUSIONS: This retrospective review of CLL clinical practice showed an important implementation of the W and W strategy with a long duration, especially in early stage cases with low RAI or Binet scores. PMID- 26838213 TI - Involvement of CELSR3 Hypermethylation in Primary Oral Squamous Cell Carcinoma. AB - BACKGROUND: Promoter hypermethylation is a frequent epigenetic mechanism for gene transcription repression in cancer and is one of the hallmarks of the disease. Cadherin EGF LAG seven-pass G-type receptor 3 (CELSR3) contributes to cell contact-mediated communication. Dysregulation of promoter methylation has been reported in various cancers. OBJECTIVES: The objectives of this study were to investigate the CELSR3 hypermethylation level in oral squamous cell carcinomas (OSCCs) using methylation-sensitive high-resolution melting analysis (MS-HRM) and to correlate CELSR3 methylation with patient demographic and clinicopathological parameters. MATERIALS AND METHODS: Frozen tissue samples of healthy subjects' normal mucosa and OSCCs were examined with regard to their methylation levels of the CELSR3 gene using MS-HRM. RESULTS: MS-HRM analysis revealed a high methylation level of CELSR3 in 86% of OSCC cases. Significant correlations were found between CELSR3 quantitative methylation levels with patient ethnicity (P=0.005), age (P=0.024) and pathological stages (P=0.004). A moderate positive correlation between CELSR3 and patient age was also evident (R=0.444, P=0.001). CONCLUSIONS: CELSR3 promoter hypermethylation may be an important mechanism involved in oral carcinogenesis. It may thus be used as a biomarker in OSCC prognostication. PMID- 26838214 TI - Psychometric Evaluation of the Colorectal Cancer Screening Belief Scale Based on Health Belief Model's Constructs for the Fecal Occult Blood Test. AB - BACKGROUND: It is important to validate scales related to cancer screening beliefs in order to better understand perceptions. The aim of this study was to test the psychometric properties of the colorectal cancer screening belief scale based on Health Belief Model (HBM) constructs. MATERIALS AND METHODS: Data were collected from 600 persons referred to outpatient laboratory units in Iran through a convenience sampling procedure. In this cross-sectional study, exploratory and confirmatory factor analyses were used to examine construct validity of scale. RESULTS: Through exploratory factor analysis, 52 items of the scale converged to five constructs of HBM with 4 items omission. Construct validity was determined by confirmatory factor analysis through which correlated model was supported. Cronbach's alpha coefficient for the whole scale was obtained as 0.78, which indicates reliability of the scale. CONCLUSIONS: The study findings showed that this scale is a valid and reliable instrument that can be used for measuring HBM constructs about colorectal cancer screening with the fecal occult blood test. PMID- 26838215 TI - Re-Examination of Opisthorchis viverrini in Nakhon Ratchasima Province, Northeastern Thailand, Indicates Continued Needs for Health Intervention. AB - Opisthorchis viverrini infection is associated with cholangiocarcinoma particularly in the cases of chronic or re-infection. This presents a serious health problem in northeastern and northern Thailand. A community base approach is required for surveillance. Therefore, in a pilot project, re-examination of O. viverrini infection was conducted in the 3 districts of Nakhon Ratchasima province, Thailand, during June and October 2015. A total of 355 participants from a 194,152 population, was selected through multi-stage sampling. O. viverrini infection was determined using modified Kato Katz thick smear technique. Participants were 229 males and 126 females, and aged >=30 years old. Prevalence of O. viverrini infection was 2.25% (8/355 participants). O. viverrini infection was slightly higher in females (3.17%), and age group between 41-50 years (4.49%). Mueang Yang district had a highest of O. viverrini infection rate (2.82%), and followed by Bua Yai (2.48%), and Chum Phuang (1.84%), respectively. O. viverrini infection rate was increased from year 2012 to 2015 particularly in Bua Yai and Mueang Yang. These re-examinion results indicate that opisthorchiasis is still problem in community of Nakhon Ratchasima province, therefore, the provincial-wide scale is need required. Furthermore health education is need intervened in the infected group, and screening of cholangiocarcinoma is urgently concerned. PMID- 26838216 TI - Incidence of Active HCV infection amongst Blood Donors of Mardan District, Pakistan. AB - Hepatitis C is an ailment of liver caused by hepatitis C virus (HCV) infection. About 3% of the world population is infected by this virus. HCV infection is a leading reason for liver cirrhosis and therefore a major source of hepatocellular carcinoma. The study focused on the incidence of active HCV infection in blood donors of Mardan district of KPK, Pakistan. A total of 5318 blood donors were inspected for the presence of anti-HCV antibodies and HCV-RNA using ICT (immune chromatographic test), ELISA and RT-PCR at Mardan Medical Complex (MMC), Mardan. Out of these, 157 (2.95%) were positive by ICT, 60 (1.12%) by ELISA and 56 (1.05%) for HCV-RNA. The frequency of active HCV infectivity amongst the blood donors from district Mardan, KPK Pakistan was 1.05 %. Application of strict measures during blood donor selection and use of proper screening assays such as ELISA in place of ICT devices can give a more accurate picture so that the incidence of this viral infection in HCV negative blood recipients can be reduced. PMID- 26838217 TI - Cervical Cancer Screening: Recommendations for Muslim Societies. AB - BACKGROUND: The overall cervical cancer incidence rate is low in Iran; however, because of a higher risk of death for cervical cancer, a disease that kills women in middle age, a cervical cancer control program is needed. The aim of this study was to provide consensus recommendation for cervical cancer prevention in Iran and other Muslim societies with low incidences of cervical cancer. MATERIALS AND METHODS: Through a practical guideline development cycle, we developed six questions that were relevant to produce the recommendation. We reviewed 190 full text records of cervical cancer in Iran (1971 to 2013) of which 13 articles were related to the data needed to answer the recommendation questions. We also reviewed World Health Organization, IARC, GLOBOCAN report, Iran Ministry of Health cancer registry report and 8 available foreign countries guidelines. Lastly, we also evaluated the Pap smear results of 825 women who participated in the Iranian HPV survey, of whom 328 were followed-up after a 5-year interval. RESULTS: The obtained data highlighted the burden of HPV and cervical cancer situation in Iran. Experts emphasized the necessity of a cervical cancer screening program for Iranian women, and recommended an organized screening program with a cytological evaluation (Pap smear) that would start at the age of 30 years, repeated every 5 years, and end at the age of 69 years. Meanwhile, there is no need for screening among women with a hysterectomy, and screening should be postponed to post-partum among pregnant women. CONCLUSIONS: An organized cervical cancer screening is a necessity for Iran as more than 500-900 women in middle age diagnosed with an invasive cervical cancer every year cannot be ignored. This recommendation should be taken into account by the National Health System of Iran and Muslim countries with shared culture and behavior patterns. CUBA HPV test could be consideration in countries Muslim country with appropriate budget, resources and facility. PMID- 26838218 TI - Relationship between erb-B2 mRNA Expression in Blood and Tissue of Invasive Ductal Carcinoma Breast Cancer Patients and Clinicopathological Characteristics of the Tumors. AB - Molecular detection methods such as RT-PCR for detecting breast cancer-associated gene expression in the peripheral blood have the potential to modify breast cancer (BC) staging and therapy. In this regard, we evaluated the potential of erb-B2 molecular marker in BC detection and analyzed the expression of erb-B2 mRNA in the peripheral blood and fresh tissue samples of 50 pretreated female BC patients and 50 healthy females by reverse transcription-PCR (RT-PCR) method. We also assessed the correlation of erb-B2 mRNA marker positivity in peripheral blood and tumor tissue samples with clinical and pathological factors in BC patients in order to evaluate its prognostic value. It was shown that there is a significant difference between healthy females and BC patients with expression of the erb-B2 molecular marker (p<0.01). A significant difference between the expression of erb-B2 in the peripheral blood and tissue samples of BC patients (p<0.01) and the frequency of circulating erb-B2 mRNA expression in peripheral blood and in tissue was detected by RT-PCR. No correlation was found between erb B2 mRNA expression in blood or tumor tissue samples and lymph node, tumor grade, tumor stage, tumor size, patient's age, ki67, estrogen receptor (ER), progesterone receptor (PGR), P53, and HER-2 status. However, in a small subset of 31 BC patients we found that expression of erb-B2 in peripheral blood or in both peripheral blood and tumor tissue was directly correlated with lympho-vascular invasion and perineural invasion as poor prognostic features. The highest rates of erb-B2 expression in peripheral blood or tumor tissue were in the ER and PR negative and HER-2 positive group. This study suggests that the application of the RT-PCR and immunohistochemical methods for erb-B2 molecular marker detection would provide a higher detection rate, especially in early stage BC. PMID- 26838219 TI - MicroRNAs and Lymph Node Metastasis in Papillary Thyroid Cancers. AB - Lymph node metastasis (LNM) in papillary thyroid cancer (PTC) has been shown to be associated with increased risk of locoregional recurrence, poor prognosis and decreased survival, especially in older patients. Hence, there is a need for a reliable biomarker for the prediction of LNM in this cancer. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene translation or degradation and play key roles in numerous cellular functions including cell-cycle regulation, differentiation, apoptosis, invasion and migration. Various studies have demonstrated deregulation of miRNA levels in many diseases including cancers. While a large number of miRNAs have been identified from PTCs using various means, association of miRNAs with LNM in such cases is still controversial. Furthermore, studies linking most of the identified miRNAs to the mechanism of LNM have not been well documented. The aim of this review is to update readers on the current knowledge of miRNAs in relation to LNM in PTC. PMID- 26838220 TI - Reliability and Validity of an Iranian Version of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Patients with Multiple Myeloma: the EORTC QLQ-MY20. AB - BACKGROUND: Reliable and validated instruments are needed in order to study the quality of life in myeloma patients. This study aimed to translate and explore the psychometric properties of the European Organisation for Research and Treatment of Cancer (EORTC) myeloma module (QLQ-MY20) in Iranian patients. MATERIALS AND METHODS: Two hundred and fifteen patients with multiple myeloma (MM) were recruited from Imam Khomeini Hospital, Tehran. A standard forward backward translation procedure was implemented. Participating patients were asked to complete the EORTC QLQ-C30 and the QLQ-MY20 three times, at study entry, after two weeks, and again after three months. Data were tested for the range of measurement, internal consistency, test-retest reliability, known group comparison, responsiveness and factor structure. RESULTS: Mean age of the patients was 60.7 years. No floor and ceiling effects were seen for the QLQ-MY20. Cronbach's alpha was greater than 0.80 for all three multi-item scales (ranging from 0.82 to 0.93). All four scales had test-retest reliability of 0.85 or greater. Results of the confirmatory factor analysis that the hypothesized 3 scale measurement model of the QLQ-MY20. Moreover, the Persian version for the QLQ-MY20 differentiated between subgroups of the patients in terms of beta-2 microglobulin, fracture and performance status. The responsiveness of the QLQ MY20 to change over time was confirmed within 3 months. CONCLUSIONS: the results of our study indicate that our Iranian version of the QLQ-MY20 is a feasible, reliable and valid questionnaire for assessing the condition-specific quality of life of patients with MM. PMID- 26838222 TI - Effect of an Educational Intervention on Knowledge of Human Papillomavirus Vaccination among Pre-University Students in Malaysia. AB - BACKGROUND: Cervical cancer is the fourth most common cancer among women worldwide. Studies evaluating the effect of health education on knowledge and perception of cervical cancer have generated conflicting results. Thus, this study aimed to evaluate the effect of educational intervention towards knowledge of HPV vacccination for cervical cancer prevention among pre-university students in Malaysia. MATERIALS AND METHODS: This was an experimental before and after study performed between October 2014 and March 2015. Five hundred and eighty students were randomly assigned into intervention and control groups. All were required to complete both pre-intervention and post-intervention questionnaires. Those in the intervention group were given an information leaflet to read before answering the post-intervention questionnaire. RESULTS: Almost half (48.3%) of the students had poor knowledge, with a score less than 5, and only 51 (8.8%) exhibited good knowledge, with a score of 11 and above. After educational intervention, the number of students with poor knowledge was reduced to 177 (29.3%) and the number of students who exhibited good knowledge increased to 148 (25.5%). Students from the intervention group demonstrated significant higher total scores in knowledge regarding 'HPV infection and cervical cancer' (p=0.000) and 'HPV vaccination and cervical cancer prevention' (p=0.000) during post intervention as compared to the control group. CONCLUSIONS: Knowledge on HPV infection and vaccination is low among pre-university students. Educational intervention in the form of information leaflets appears effective in creating awareness and improving knowledge. PMID- 26838221 TI - Influence of Genotype and Haplotype of MDR1 (C3435T, G2677A/T, C1236T) on the Incidence of Breast Cancer--a Case-Control Study in Jordan. AB - BACKGROUND: Breast cancer is the leading cause of cancer death among women and the second in humans worldwide. Many published studies have suggested an association between MDR1 polymorphisms and breast cancer risk. Our aim was to study the association between genetic polymorphism of MDR1 at three sites (C3435T, G2677A/T, and C1236T) and their haplotype and the risk of breast cancer in Jordanian females. MATERIALS AND METHODS: A case-control study involving 150 breast cancer cases and 150 controls was conducted. Controls were age-matched to cases. The polymerase chain reaction/restriction fragment length polymorphism (PCR- RFLP) technique and sequencing were performed to analyse genotypes. RESULTS: The distribution of MDR1 C3435T genotypes differed between cases and controls [cases, CC 45.3%, CT 41.3%, and TT 13.3%; controls, CC 13.4%, CT 43.3%, and TT 30.2%, p < 0.001]. Similarly, the distribution of G2677A/T significantly differed [cases, GG 43.1 %, GT+GA 50.9% and AA+TT 6%; controls, GG 29.6 %, GT+GA 50.9%, and AA+TT 19.4%, p = 0.004]. On the other hand, genotype and allelotype distribution of C1236T was not statistically different between cases and controls (p=0.56 and 0.26, respectively). The CGC haplotype increased the risk to breast cancer by 2.5-fold compared to others, while TGC and TTC haplotypes carried 2.5- and 5-fold lower risk of breast cancer, respectively. CONCLUSIONS: Genetic polymorphisms of MDR1 C3435T and G2677A/T, but not C1236T, are associated with increased risk of breast cancer. In addition, CGC, TGC and TTC haplotypes have different impacts on the risk of breast cancer. Future, larger studies are needed to validate these findings. PMID- 26838223 TI - Support for a Campus Tobacco-Free Policy among Non- Smokers: Findings from a Developing Country. AB - BACKGROUND: A tobacco-free workplace policy is identified as an effective means to reduce tobacco use and protect people from second-hand smoke; however, the number of tobacco-free policies (TFP) remains very low in workplaces in Malaysia. This study explored the factors affecting support for a tobacco-free policy on two healthcare campuses in Malaysia, prior to the implementation of TFP. MATERIALS AND METHODS: This cross- sectional study was conducted among 286 non smokers from two healthcare training centres and two nearby colleges in Malaysia from January 2015 to April 2015. A standardized questionnaire was administered via staff and student emails. The questionnaire collected information on sociodemographic characteristics, support for a tobacco-free policy and perceived respiratory and sensory symptoms due to tobacco exposure. Bivariate and multivariate logistic regression analyses were performed to estimate the independent effects of supporting a tobacco-free campus. RESULTS: The percentage of individuals supporting completely tobacco-free facilities was 83.2% (N=238), as opposed to 16.7% (N=48) in support of partially tobacco-free facilities. Compared to the supporters of partially tobacco-free facilities, non-smokers who supported completely tobacco-free health facilities were more likely to be female, have higher education levels, to be very concerned about the effects of other people smoking on their health and to perceive a tobacco-free policy as very important. In addition, they perceived that tobacco smoke bothered them at work by causing headaches and coughs and, in the past 4 weeks, had experienced difficulty breathing. In the multivariate model, after adjusting for sociodemographic characteristics and other factors, only experiencing coughs and headaches increased the odds of supporting a completely tobacco-free campus, up to 2.5- and 1.9-fold, respectively. CONCLUSIONS: Coughs and headaches due to other people smoking at work enhances support for a completely tobacco-free campus among non-smokers. PMID- 26838224 TI - Serum Antibody Ig G and Ig M Titers for Opisthorchis felineus Correlate with Eggs in Faeces--a Comprehensive Study in Chuvash Republic, Russia. AB - The Cholangiocarcinoma is a. The risk of development of cholangiocarcinoma, generally a rare type of a liver tumor, increases during infection of Opisthorchiasis. For this reason the timely detection of Opisthorchiasis is important for Cholangiocarcinoma prevention. There are many studies which concern the detection of pathogenesis of Opisthorchis viverrini infection but a little known about Opisthorchis felineus. In this study we investigate a correlation of the eggs which are found in a faeces and are comparable with a serum Ig G and Ig M antibody level that were detected with ELISA test in a large group of patients. The result is showing positive correlation between evidence of the Opisthorchis felineus eggs that were found in a faeces and antibody Ig G and Ig M level in a serum. Moreover the combination of two methods can improve the Opisthorchiasis diagnostic: the serum antibody and faeces investigation of eggs. PMID- 26838225 TI - Antibiotic Resistant Pattern of Helicobacter Pylori Infection Based on Molecular Tests in Laos. AB - BACKGROUND: The efficacy of standard treatment of Helicobacter pylori (H. pylori) is declining because of antibiotic resistance. Clarithromycin resistance is also increasing in many Asian countries. The aim of this study was to determine the antibiotic susceptibility patterns of H. pylori infection and clinical association in Laos. MATERIALS AND METHODS: A total of 329 Lao dyspeptic patients who underwent gastroscopy at Mahosot Hospital, Vientiane, Laos during December 2010-March 2012 were enrolled in this study. During gastroscopy, 4 biopsies were collected (2 each from the antrum and body) for CLO-test and histopathology. Only the positive CLO-test gastric tissues was stored at -80 degrees in a freezer until DNA was extracted and a GenoType(r)HelicoDR test was conducted for detecting mutations in the rrl gene encoding 23S rRNA (clarithromycin resistance) and mutations in gyrA gene (fluoroquinolone resistance) . RESULTS: Of the total, 119 Lao patients (36.2%) were infected with H. pylori including 59 males (49.6%) and 60 females (50.4%) with a mean age of 46 years. Clarithromycin and fluoroquinolone resistance of H. pylori infection was demonstrated in 15 (12.6%) and 16 strains (13.4%) respectively. In clarithromycin resistance, the number of patients who had education above primary school and BMI>= 25 kg/m2 were significantly higher than those who had education below primary school and BMI< 25 kg/m2 (23.1% vs 7.5%, P-value= 0.036 and 20.5% vs 8%, P-value= 0.048, respectively). In fluoroquinolone resistance, the number of lowland Lao was significantly higher than those of non- lowland (highland and midland) Lao ethnic groups (16.7% vs 0%, P-value= 0.039). CONCLUSIONS: H. pylori infections remain common in Laos. Clarithromycin and fluoroquinolone resistance with H. pylori infection are growing problems. Education above primary school and BMI >= 25 kg/m2 might be predictors for clarithromycin resistance and lowland Lao ethnicity might be predictors for fluoroquinolone resistance with H. pylori infection in Laos. PMID- 26838226 TI - Clinicopathological Significance of S100A10 Expression in Lung Adenocarcinomas. AB - BACKGROUND: S100A10, of the S100 protein family, is reported to be involved in cancer cell invasion and metastasis. The aims of the present study were to immunohistochemically examine S100A10 expression in surgically resected lung adenocarcinomas, and evaluate any relationships with clinicopathological parameters and prognosis of patients. MATERIALS AND METHODS: S100A10 expression was immunohistochemically studied in 202 consecutive resected lung adenocarcinomas, and its associations with clinicopathological parameters were evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of S100A10 expression on survival. RESULTS: S100A10 expression was detected in 65 of the 202 (32.2%) lung adenocarcinomas, being significantly correlated with poorer differentiation (P =0.015), a higher pathological TNM stage (stages II and III) (P=0.004), more frequent and severe intratumoral vascular invasion (P=0.001), and a poorer prognosis (P=0.030). However, S100A10 expression was not an independent predictor of survival after controlling for clinicopathological factors. CONCLUSIONS: The present study reveals that S100A10 is expressed in a subset of lung adenocarcinomas, and this is related to some clinicopathological parameters, although further studies are required to confirm the correlation between S100A10 expression and prognosis of lung adenocarcinoma patients. PMID- 26838227 TI - Relationship between HER2 Proto-oncogene Status and Prognostic Factors of Breast Cancer in the West of Iran. AB - BACKGROUND: Breast cancer is a very common health problem in Iranian women. The HER2-neu gene is a transmembrane receptor tyrosine kinase with homology to members of the EGF receptor family. The aim of this study was to investigate the association between HER2-neu oncogene status with prognostic factors of breast cancer in Kermanshah province, Iran. MATERIALS AND METHODS: Relationship between HER2-neu and prognostic factors of 130 cases of breast cancer were evaluated during two years in Imam Reza hospital in Kermanshah, Iran. Data were analyzed using descriptive statistics and the T-test and Mann-Whitney U non-parametric test using SPSS 19. RESULTS: The mean age for the patients was 46.0+/-8.0 years, all being female. Among the predictive factors for breast cancer were family history, stage of disease, involvement of the lymphovascular system, number of involved lymph nodes in axillaries, grading and hormone receptor status with HER2 neu oncogene had direct correlation and between factors, tumor location, patient age and histological characteristics and HER2-neu oncogene had no significant relationship. We found significant correlation between HER2 with ER and PR and also HER2 with ER, PR negative. CONCLUSIONS: HER2-neu is risk factor that can be a good prognostic and also predictive factor. For these reasons, we recommend that it be evaluated for all types of BC. PMID- 26838228 TI - Knowledge and Attitudes of Medical and Non-Medical Turkish University Students about Cervical Cancer and HPV Vaccination. AB - BACKGROUND: This study was conducted to determine knowledge, attitudes and practices about cervical cancer and HPV vaccination of students studying in various faculties of Erciyes University. MATERIALS AND METHODS: The study was performed among the first and fourth grade students of Medicine, Theology, Education and Economics and Administrative Sciences (FEAS) faculties of Erciyes University. It was aimed to reach 1,073 students and 718 were evaluated. A questionnaire consisting of 48 questions related to the socio-demographic characteristics, knowledge, attitude and practices about cervical cancer and HPV vaccination was administered to the students. The chi-square test and logistic regression were used for the statistical analyses. RESULTS: Of the students, 78.3% were aware of cervical cancer, while 36.1% of them were aware of the HPV vaccine. The percentage hearing about cervical cancer and HPV vaccination was significantly higher among the students of the medical faculty than the others and among fourth grade students comparing with the first grade. The marital status and the presence of a health worker in the family had no significant impact on the knowledge level of the students. The acceptability of the HPV vaccination was low among all students. CONCLUSIONS: The knowledge levels of the university students about cervical cancer and HPV vaccination are inadequate. This deficiency is more pronounced among the non-medical students and there is no significant increase during the faculty years. Non-medical students must be provided with information about important public health issues by elective courses. HPV vaccination could provide many benefits for men and women by decreasing the morbidity and mortality of cervical, anal, and penile cancers. PMID- 26838229 TI - Prevention of Esophageal Cancer: Experience of an Educational Campaign for Reducing Hot Tea Consumption in Iran. AB - BACKGROUND: Given the association between drinking hot tea and the risk of esophageal squamous cell carcinoma, this study was designed to determine the effectiveness of an educational campaign based on the Theory of Planned Behavior (TPB) in reducing hot tea consumption among a sample of Iranian female students. MATERIALS AND METHODS: In this quasi-experimental study, 130 primary-school female students in Salas Babajani, Kermanshah, Iran were randomly selected. A two month campaign based on TPB constructs was developed and conducted for the intervention group. Combined mass media approaches (such as posters, pamphlet, and brochure) with small group and individual activities were used to transfer the campaign messages. Also, five 40-minute instructional sessions for the students and one session for their parents and teachers were held. The hot tea consumption, attitude, subjective norms, perceived behavioral control and no intention to drink hot tea were variables which were measured at baseline and again after 4 weeks. RESULTS: There was a significant improvement in the perceived behavioral control and intention to drink no hot tea variables in the intervention group as compared to the control group following the campaign. In addition, significant reductions were found for the hot tea consumption and favorable attitude toward drinking hot tea in the intervention group as compared to the control group. CONCLUSIONS: Conducting educational campaigns based on TPB variables may reduce hot tea consumption among Iranian students. PMID- 26838230 TI - Nurses, Healthy Women and Preventive Gynecological Examinations--Vlora City Scenario, Albania. AB - BACKGROUND: Nurses play an important role in preventive medicine because they represent the largest sector of health professionals. This role is very crucial in developing countries, which are going through rapid societal and economic changes, associated with a rising burden of cancers due to different risk factors. The current study aimed to compare health awareness between nurses and healthy women regarding preventive gynecological examinations and to answer the question - can nurses make a difference in women's health? MATERIALS AND METHODS: This cross sectional research included a total of 150 women, 70 nurses and 80 healthy women, randomly selected. Data were collected in 2014 in Vlora city through a self-administered questionnaire that assessed different variables about preventive gynecological examinations. RESULTS: Cervical screening rates were 20.3% and 41.8%, respectively, for nurses and healthy women, despite the former having a statistical significant greater knowledge of risk factors and symptoms. CONCLUSIONS: Even if the health awareness of nurse participants can be considered good, they need themselves to increase participation rates in cervical screening if they are to provide role models for health education/promotion addressing misconceptions and barriers. PMID- 26838231 TI - Antiproliferative Evaluation and Apoptosis Induction in MCF- 7 Cells by Ziziphus spina christi Leaf Extracts. AB - BACKGROUND: Herbal medicine has becoming a potential source of treatment for different types of cancer including breast cancer. It has been shown that plants from the family Rhamnaceae possess anticancer activity. OBJECTIVE: In this study, we determined the antiproliferative influence of Ziziphus spina christi- a species from this family- on the MCF-7 (human breast adenocarcinoma) cell line. MATERIALS AND METHODS: The cytotoxicity of the total extract, ethanol, ethanol aqueous (1:1) as well as aqueous fractions of Ziziphus spina christi leaves was evaluated through MTT assay against MCF-7 cell line. Cell cycle inhibition and apoptosis induction were assessed by flowcytometry cycle RNase/PI analysis and Annexin V-FLUOS, respectively. Apoptosis was also analyzed by immunoblotting assay. RESULTS: Our results indicated that the ethanolic fraction had the lowest IC50 value (0.02 mg/ml), induced cell cycle arrest at the G1/S phase as well as apoptosis after a 48h of treatment. CONCLUSIONS: This is the first report on anticancer effect of Ziziphus spina christi ethanolic fraction on breast cancer cells, providing a scientific basis for its utility in traditional medicine. However, further in-depth studies are needed to confirm the precise mechanisms. PMID- 26838232 TI - Tissue CA125 and HE4 Gene Expression Levels Offer Superior Accuracy in Discriminating Benign from Malignant Pelvic Masses. AB - BACKGROUND: Ovarian cancer remains a major worldwide health care issue due to the lack of satisfactory diagnostic methods for early detection of the disease. Prior studies on the role of serum cancer antigen 125 (CA125) and human epididymis protein 4 (HE4) in detecting ovarian cancer presented conflicting results. New tools to improve the accuracy of identifying malignancy are urgently needed. We here aimed to evaluate the diagnostic utility of tissue CA125 and HE4 gene expression in comparison to serum CA125 and HE4 in discriminating benign from malignant pelvic masses. MATERIALS AND METHODS: One-hundred Egyptian women were enrolled in this study, including 60 epithelial ovarian cancer (EOC) patients and 20 benign ovarian tumor patients, as well as 20 apparently healthy women. Preoperative serum levels of CA125 and HE4 were measured by immunoassays. Tissue expression levels of genes encoding CA125 and HE4 were determined by quantitative real time polymerase chain reaction (qRT-PCR). The diagnostic performance of CA125 and HE4, measured either as mRNA or protein levels, was evaluated by receiver operating characteristic (ROC) curves. RESULTS: The serum CA125+HE4 combination and serum HE4, with area under the curve (AUC) values of 0.935 and 0.932, respectively, performed significantly better than serum CA125 (AUC=0.592; P<0.001). Tissue CA125 and HE4 (AUC=1) performed significantly better than serum CA125 (P<0.001), serum HE4 (P=0.016) and the serum CA125+HE4 combination (P=0.018). CONCLUSIONS: Measurement of tissue CA125 and HE4 gene expression not only improves discriminatory performance, but also broadens the range of differential diagnostic possibilities in distinguishing EOC from benign ovarian tumors. PMID- 26838233 TI - Usefulness of Salivary and Serum Auto-antibodies Against Tumor Biomarkers HER2 and MUC1 in Breast Cancer Screening. AB - BACKGROUND: The aim of this work was to investigate if serum and salivary auto antibodies, isotypes IgG and IgM, against HER2 and MUC1 tandem repeat fragments could play a role in breast cancer screening. MATERIALS AND METHODS: Our case control study was conducted in breast cancer patients, in early stages (n=29), at the gynecology service, Maternity Souissi Hospital, Rabat, Morocco and healthy woman (n=31). Salivary and serum auto-antibodies against HER2 and MUC1 (tandem repeat) were assessed by enzyme-linked immunosorbent assay (ELISA) and compared between patients and healthy women using the Mann-Whitney U test. A P-value <0.05 was considered to be statistically significant. RESULTS: Our data showed higher expression of all serum and salivary autoantibodies in patients as compared to healthy women p<0.05. However, serum IgM anti-MUC1 expression did not show a significant difference between cases and controls (p=0.79). Similarly, salivary IgG anti-HER2 expression did not differ (p=0.15). The correlation between the different isotypes of antibodies revealed that the highest correlation was between salivary IgG anti-HER2 and salivary IgG anti- MUC1(r=0.65). In fact, we have found in saliva the correlation between autoantibodies anti-MUC1 and anti HER2 more important than in serum (r=0.59 and r=0. 55). However, the correlation between serum and saliva values for all antibodies was weak. CONCLUSIONS: Autoantibodies against HER2 and MUC1 may provide a useful approach in breast cancer screening when using both serum and saliva values. PMID- 26838234 TI - Helicobacter Pylori Associated Gastritis Increases Risk of Colorectal Polyps: a Hospital Based-Cross-Sectional Study in Nakhon Ratchasima Province, Northeastern Thailand. AB - BACKGROUND: Colorectal polyps are common in Thailand, particularly in the northeastern region. The present study aimed to determine any correlation between Helicobacter pylori-associated gastritis and colorectal polyps in the Thai population. MATERIALS AND METHODS: A total of 303 patients undergoing esophagogastroduodenoscopy with colonoscopy for investigation of chronic abdominal pain participated in this study from November 2014 to October 2015. A diagnosis of Helicobacter pylori associated gastritis was made if the bacteria were seen on histopathological examination and a rapid urease test was positive. Colorectal polyps were confirmed by histological examination of colorectal biopsies. Patient demographic data were analyzed for correlations. RESULTS: The prevalence of colorectal polyps was 77 (25.4%), lesions being found more frequently in Helicobacter pylori infected patients than non-infected subjects [38.4% vs. 12.5%; Odds Ratio (OR) (95% CI): 2.26 (1.32 - 3.86), p < 0.01]. Patients with Helicobacter pylori - associated gastritis were at high risk of having adenomas featuring dysplasia [OR (95% CI): 1.15 (1.16 - 7.99); P = 0.02]. There was no varaition in location of polyps, age group, sex and gastric lesions with respect to Helicobacter pylori status. CONCLUSIONS: This study showed that Helicobacter pylori associated gastritis is associated with an increased risk of colorectal polyps, especially adenomas with dysplasia in the Thai population. Patients with Helicobacter pylori-associated gastritis may benefit from concurrent colonoscopy for diagnosis of colorectal polyps as a preventive and early treatment for colorectal cancer. PMID- 26838235 TI - Analysis of SEER Adenosquamous Carcinoma Data to Identify Cause Specific Survival Predictors and Socioeconomic Disparities. AB - BACKGROUND: This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) adenosquamous carcinoma data to identify predictive models and potential disparities in outcome. MATERIALS AND METHODS: This study analyzed socio-economic, staging and treatment factors available in the SEER database for adenosquamous carcinoma. For the risk modeling, each factor was fitted by a generalized linear model to predict the cause specific survival. An area under the receiver operating characteristic curve (ROC) was computed. Similar strata were combined to construct the most parsimonious models. RESULTS: A total of 20,712 patients diagnosed from 1973 to 2009 were included in this study. The mean follow up time (S.D.) was 54.2 (78.4) months. Some 2/3 of the patients were female. The mean (S.D.) age was 63 (13.8) years. SEER stage was the most predictive factor of outcome (ROC area of 0.71). 13.9% of the patients were un-staged and had risk of cause specific death of 61.3% that was higher than the 45.3% risk for the regional disease and lower than the 70.3% for metastatic disease. Sex, site, radiotherapy, and surgery had ROC areas of about 0.55-0.65. Rural residence and race contributed to socioeconomic disparity for treatment outcome. Radiotherapy was underused even with localized and regional stages when the intent was curative. This under use was most pronounced in older patients. CONCLUSIONS: Anatomic stage was predictive and useful in treatment selection. Under-staging may have contributed to poor outcome. PMID- 26838236 TI - Analysis of SEER Glassy Cell Carcinoma Data: Underuse of Radiotherapy and Predicators of Cause Specific Survival. AB - BACKGROUND: This study used receiver operating characteristic curve to analyze Surveillance, Epidemiology and End Results (SEER) for glassy cell carcinoma data to identify predictive models and potential disparities in outcome. MATERIALS AND METHODS: This study analyzed socio-economic, staging and treatment factors. For risk modeling, each factor was fitted by a generalized linear model to predict the cause specific survival. Area under the receiver operating characteristic curves (ROCs) were computed. Similar strata were combined to construct the most parsimonious models. A random sampling algorithm was used to estimate modeling errors. Risk of glassy cell carcinoma death was computed for the predictors for comparison. RESULTS: There were 79 patients included in this study. The mean follow up time (S.D.) was 37 (32.8) months. Female patients outnumbered males 4:1. The mean (S.D.) age was 54.4 (19.8) years. SEER stage was the most predictive factor of outcome (ROC area of 0.69). The risks of cause specific death were, respectively, 9.4% for localized, 16.7% for regional, 35% for the un staged/others category, and 60% for distant disease. After optimization, separation between the regional and unstaged/others category was removed with a higher ROC area of 0.72. Several socio-economic factors had small but measurable effects on outcome. Radiotherapy had not been used in 90% of patients with regional disease. CONCLUSIONS: Optimized SEER stage was predictive and useful in treatment selection. Underuse of radiotherapy may have contributed to poor outcome. PMID- 26838237 TI - Demographic and Clinical Characteristics of Adult Acute Myeloid Leukemia- Tertiary Care Experience. AB - BACKGROUND: Acute myeloid leukemia (AML) is an acquired clonal frequent malignant disorder of myeloid progenitor cells. Our aim was to study demographical and clinicopathological features of adult Pakistani AML patients at presentation. MATERIALS AND METHODS: In this single centre study extending from January 2010 to December 2014, data were retrieved from the patient records with a predetermined performa and analyzed with SPSS version 22. RESULTS: Overall 125 patients were diagnosed at our institution with de novo AML during the study period. There were 76 males and 49 females (ratio 1.5:1), with an age range between 15 and 85 years and a mean age of 38.8+/-20.1 years. The major complaints were fever (72.8%), generalized weakness (60%), bleeding (37.6%) and dyspnea (12%). Physical examination revealed pallor in 56.8%, splenomegaly and hepatomegaly in 16% and 12.8%, respectively, and lymphodenopathy in 10.4%. The mean hemoglobin was 8.19+/ 2.12g/dl with a mean MCV of 86.0+/-9.83 fl, a mean total leukocyte count of 43.1+/-68.5x109/l, an ANC of 3.09+/-6.66x109/l and a mean platelet count of 62.3+/-78.6x109/l. CONCLUSIONS: AML in Pakistani patients is seen in a relatively very young population with male preponderance, compared with the west. However, clinico-pathological features appear comparable to published data. PMID- 26838238 TI - High Incidence of Breast Cancer in Light-Polluted Areas with Spatial Effects in Korea. AB - We have reported a high prevalence of breast cancer in light-polluted areas in Korea. However, it is necessary to analyze the spatial effects of light polluted areas on breast cancer because light pollution levels are correlated with region proximity to central urbanized areas in studied cities. In this study, we applied a spatial regression method (an intrinsic conditional autoregressive [iCAR] model) to analyze the relationship between the incidence of breast cancer and artificial light at night (ALAN) levels in 25 regions including central city, urbanized, and rural areas. By Poisson regression analysis, there was a significant correlation between ALAN, alcohol consumption rates, and the incidence of breast cancer. We also found significant spatial effects between ALAN and the incidence of breast cancer, with an increase in the deviance information criterion (DIC) from 374.3 to 348.6 and an increase in R2 from 0.574 to 0.667. Therefore, spatial analysis (an iCAR model) is more appropriate for assessing ALAN effects on breast cancer. To our knowledge, this study is the first to show spatial effects of light pollution on breast cancer, despite the limitations of an ecological study. We suggest that a decrease in ALAN could reduce breast cancer more than expected because of spatial effects. PMID- 26838239 TI - Acute Myeloid Leukemia: Clinical Spectrum of 125 Patients. AB - BACKGROUND: Acute myeloid leukemia is an acquired clonal heterogeneous stem cell disorder. Hence, various parameters are sought out to categorize this disease into subtypes, so that as a consequence specific treatment modalities can be offered. Conventionally, the practically used method for classification utilizes French American British (FAB) criteria based on morphology and cytochemistry. The aim of present study was to determine the current spectrum of AML sub types in patients in Karachi. MATERIALS AND METHODS: This single centre cross sectional study was conducted at Liaquat National Hospital, Karachi, extending from January 2010 to December 2014. Data were retrieved from archives were analyzed with SPSS version 22. RESULTS: A total of 125 patients were diagnosed at our institution with de novo AML during five years period, 76 males and 49 females. Median age was 34.5 years. AML-M1 was the predominant FAB subtype (23.2%) followed by M2 (18.4%), M3 and M4 (16% each), M0 (14.4%), M5 (7.2%), M6 (3.2%) and M7 (1.6%). CONCLUSIONS: AML in Pakistani patients is seen in a relatively young population. The most common FAB subtype observed in our study was acute myeloblastic leukemia, without maturation (M1). PMID- 26838240 TI - Helicobacter Species are Possible Risk Factors of Cholangiocarcinoma. AB - Several infectious agents are considered to be causes of cancer in human, mainly hepatitis B and C viruses, high-risk human pailloma viruses, Helicobacter pylori, Clonorchis sinensis, and Opisthorchis viverrini. Here we described the evident research and the association between Helicobacter spp. and biliary tract cancer particularly cholangiocarcinoma (CCA). Global epidemiological studies have suggested that Helicobacter spp. are possible risk factors for biliary tract diseases. Molecular studies support a linkage of Helicobacter spp. with CCA development. H. pylori, H. bilis, and H. hepaticus, are found in CCA, but the most common species are H. pylori and H. bilis. The type of CCA are associated with Helicobacter spp. include extrahepatic CCA, and common bile duct cancer. Up to the present, however, the results from different regions, materials and methods, sub-sites of cancer, and controls have not been consistent, thus introducing heterogeneity. Therefore, a comparison between co-Helicobacter spp. CCA in the countries with low and high incident of CCA is required to settle the question. Furthermore, clarifying variation in the role of Helicobacter species in this CCA, including pathogenesis of CCA through enhanced biliary cell inflammation and proliferation, is necessary. PMID- 26838241 TI - Detection of the Carcinogenic Liver Fluke Opisthorchis viverrini Using a Mini Parasep SF Faecal Parasite Concentrator. AB - The Mini Parasep SF fecal parasite concentrator (MPSFC) is a new modification of the closed concentration system, which can easily be adopted in any routine clinical pathology laboratory. Here we describe our experience with the system in diagnosing Opisthorchis viverrini. A total of 199 fecal samples was submitted for routine examination in the clinical pathology laboratory of Suranaree University of Technology hospital, Nakhon Ratchasima province, Thailand, during August to October 2015. Out of all samples examined, 10 (5.03%) were positive with intestinal parasites including O. viverrini (2.01%), followed by Strongyloided stercoralis (1.51%), Hookworm (0.5%), Taenia spp. (0.5%), and Entamoeba coli (0.5%). Regarding the distribution of intestinal parasites in relation to the methods used, and found that 4 samples (2.01%) were positive using the direct wet smear method while 10 (5.03%) were positive with the Mini Parasep SF method; the difference was statistically significant (X2-test = 116.506, p-value =0.001). Mean time for processing using the Parasep system was 6.03 min/ sample, the conventional direct wet smear method at 0.3 min/sample. Cost per test, conventional direct wet smear method costing less than the Parasep method at USD 0.74/sample versus USD 1.47/sample. This first report of O. viverrini detection using MPSFC indicates that Parasep concentration test is useful in the routine laboratory, increasing the yield of parasites as compared to direct microscopy, but with greater processing time and cost. Further comparisons between the Parasep concentration test and common methods for O. viverrini detection are required, particularly concerning use in epidemiological surveys. PMID- 26838242 TI - Risk Factors Associated with Thyroid Carcinoma in North Pakistan. AB - BACKGROUND: Epidemiological data on thyroid cancer and associated risk factors are scarce in our setting. The present study was therefore designed to gather data which could be helpful in providing insights to thyroid physicians and surgeons for better management of affected patients. PURPOSE: To determine the frequency of carcinoma thyroid among patients presenting with goiter and its association with TSH, Tg/ATg and other demographic factors. MATERIALS AND METHODS: A total of 73 adult patients of either gender with solitary solid cold nodules and/or multi-ndoular goiter (MNG) with predominant solid cold nodules were enrolled. All surgically resected samples were sent for histopathology. The frequency of thyroid cancer and its subtypes was noted and tested for association with gender, age (< or >=40 years), recent increase in swelling size, TSH, Tg and ATg. RESULTS: Thyroid cancer was diagnosed in 26% (n=19) of the patients, 14 (73.7%) being diagnosed with papillary thyroid cancer and 5 (26.3%) with follicular thyroid cancer. No other subtypes were noted. Presence of thyroid cancer was significantly associated with recent increase in swelling size and higher TSH Values mean TSH values (P<0.05). No significant association was found with gender, age, Tg and ATg values (P>0.05). CONCLUSIONS: Overall percentage of thyroid cancer in our study sample was found to be 26%, with a predominance of papillary over follicular lesions. Rates were significantly higher in patients who had history of recent increase in swelling size and higher and higher pre surgery TSH values. PMID- 26838243 TI - Epidemiology, Incidence and Mortality of Bladder Cancer and their Relationship with the Development Index in the World. AB - BACKGROUND: Bladder cancer is an international public health problem. It is the ninth most common cancer and the fourteenth leading cause of death due to cancer worldwide. Given aging populations, the incidence of this cancer is rising. Information on the incidence and mortality of the disease, and their relationship with level of economic development is essential for better planning. The aim of the study was to investigate bladder cancer incidence and mortality rates, and their relationship with the the Human Development Index (HDI) in the world. MATERIALS AND METHODS: Data were obtained from incidence and mortality rates presented by GLOBOCAN in 2012. Data on HDI and its components were extracted from the global bank site. The number and standardized incidence and mortality rates were reported by regions and the distribution of the disease were drawn in the world. For data analysis, the relationship between incidence and death rates, and HDI and its components was measured using correlation coefficients and SPSS software. The level of significance was set at 0.05. RESULTS: In 2012, 429,793 bladder cancer cases and 165,084 bladder death cases occurred in the world. Five countries that had the highest age-standardized incidence were Belgium 17.5 per 100,000, Lebanon 16.6/100,000, Malta 15.8/100,000, Turkey 15.2/100,000, and Denmark 14.4/100,000. Five countries that had the highest age-standardized death rates were Turkey 6.6 per 100,000, Egypt 6.5/100,000, Iraq 6.3/100,000, Lebanon 6.3/100,000, and Mali 5.2/100,000. There was a positive linear relationship between the standardized incidence rate and HDI (r=0.653, P<0.001), so that there was a positive correlation between the standardized incidence rate with life expectancy at birth, average years of schooling, and the level of income per person of population. A positive linear relationship was also noted between the standardized mortality rate and HDI (r=0.308, P<0.001). There was a positive correlation between the standardized mortality rate with life expectancy at birth, average years of schooling, and the level of income per person of population. CONCLUSIONS: The incidence of bladder cancer in developed countries and parts of Africa was higher, while the highest mortality rate was observed in the countries of North Africa and the Middle East. The program for better treatment in developing countries to reduce mortality from the cancer and more detaiuled studies on the etiology of are essential. PMID- 26838244 TI - Lack of Association between CYP1A1 M2 and M4 Polymorphisms and Breast Carcinoma in Jordanian Women: a Case-Control Study. AB - BACKGROUND: CYP1A1 is a candidate gene for low-penetrance breast cancer susceptibility, as it plays an important role in the metabolism of carcinogens and estrogens. PURPOSE: The objective of this study was to assess the association between M2 (A2455G, Ile462Val) and M4 (C2453A, Thr461Asn) polymorphisms in CYP1A1 and breast cancer risk among Jordanian women and in subgroups stratified by menopausal status and smoking history. MATERIALS AND METHODS: Blood samples were collected from 112 breast cancer female patients and 115 age-matched controls who underwent breast cancer screening with imaging and showed negative results (BI- RADS I or BI-RADS II). Genotyping was performed using the PCR-RFLP technique. RESULTS: No statistically significant overall association was found between breast cancer risk and CYP1A1 M2 genotypes (p-value = 0.55; OR = 0.77; 95% CI= 0.32 - 1.83) nor with the M4 polymorphism (p-value= 0.95; OR= 0.95; 95% CI= 0.51- 1.88). Analysis of subgroups defined by menopausal status or smoking history also revealed no association with these polymorphisms. Furthermore, the four identified haplotypes (AC; AA; GC and GA) were equally distributed among cases and controls, and haplotype analysis showed a strong linkage disequilibrium of both studied loci in either cases or controls (D'=1). CONCLUSIONS: Based on the study results, CYP1A1 M2 and M4 polymorphisms do not seem to play a major role in breast cancer risk among Jordanian females. PMID- 26838245 TI - The Immunotyping Distribution of Serum Monoclonal Paraprotein and Environmental Impact on Multiple Myeloma (MM) and Monoclonal Gammopathy of Uncertain Significance (MGUS) in Taiwan: A Medical Center-Based Experience. AB - BACKGROUND: Whether ambient exposure to environmental pollutants leads to hematopoietic malignancies such as multiple myeloma (MM) remains to be ascertained. Therefore, we aimed to investigate the immunotyping distribution of serum monoclonal paraprotein and the environmental influence on MM and monoclonal gammopathy of uncertain significance (MGUS) in the Taiwanese population. MATERIALS AND METHODS: Serum protein electrophoresis with immunosubtraction by the capillary zone electrophoresis method was performed as primary screening for MM and MGUS. Clinical, pathological, and residence data of patients were also obtained. RESULTS: From August, 2013 to June, 2015, a total of 327 patients underwent serum protein electrophoresis with immunosubtraction. Among these, 281 demonstrated no remarkable findings or non-malignant oligoclonal gammopathy, 23 were detected to have MGUS, 18 were identified as MM, and a further 5 were found as other malignancies. The most frequent immunotyping distribution of serum monoclonal paraprotein was IgG kappa (54.3%, n=25), followed by IgA lambda (15.2%, n=7) and IgG lambda (10.9%, n=5) in subjects with gammopathy. Additionally, it was shown that the elderly (OR: 4.61, 95% CI: 1.88-11.30, P<0.01) and males (OR: 2.04, 95% CI: 1.04-4.02, P=0.04) had significantly higher risk of developing MM and MGUS. There was no obvious impact of environmental factors on the health risk of MM and MGUS evolution (OR: 0.77, 95% CI: 0.40-1.50, P=0.49). CONCLUSIONS: The most frequent immunotyping distribution of serum monoclonal paraprotein included IgG kappa, IgA lambda and IgG lambda in MM and MGUS in the Taiwanese population. The elderly and male subjects are at significantly higher risk of MM and MGUS development, but there was no obvious impact of environmental factors on risk. PMID- 26838246 TI - Cholangiocarcinoma Patient Outcome in Northeastern Thailand: Single-Center Prospective Study. AB - BACKGROUND: Cholangiocarcinoma is relatively rare worldwide. Most previous reports collected only patients with pathological diagnosis. In fact, however, many patients coming to hospital are diagnosed by clinical suspicion with radiologic imaging and receive treatment without histological confirmation. Real survival data and outcome of each treatment, especially for patients that do not have histologic confirmation, are lacking. In this study, therefore, we aimed to analyze the survival rates of CCA patients and the proportions of patients receiving different treatments. MATERIALS AND METHODS: A total of 270 patients clinically suspected of CCA and visiting Srinagarind Hospital in May-July 2010, were prospectively followed until December 2014. After checking their clinical records, 163 of 270 patients were finally diagnosed as having CCA, and the data of this group were analyzed for survival rate and received treatments. RESULTS: Of the 163 patients, 96 (58.9%) had intrahepatic, 56 (34.4%) had perihilar and 11 (6.7%) had distal CCA. The majority [107 (65.6%, 95%CI, 57.8-73.0)] received only supportive care. Overall median survival was 4 months (95%CI, 3.3-4.7), and 2 years survival was only 8.1% (95%CI,4.5-12.9). However, the 4 year survival of the R0 resection group was 100%. CONCLUSIONS: The present results show that the prognosis of CCA is very poor in North-east Thailand. Most CCA patients receive only treatment to alleviate symptoms due to their advanced stage of disease. Complete surgical resection at the early stage is the only treatment that significantly improves patient survival. PMID- 26838247 TI - Thyroid Cancer Epidemiology in Iran: a Time Trend Study. AB - BACKGROUND: Considering the rising incidence of thyroid cancer worldwide, the aim of our study was to investigate the temporal trends in the incidence of this cancer in a large population of Iranian patients. MATERIALS AND METHODS: We used the Iran Cancer Data System (ICDS) Registry to assess the thyroid cancer trend from 2004 to 2010 with regard to different genders, age groups, and morphologies. To do this we analyzed the data of 10,913 new cases of thyroid cancer that occurred during these years. RESULTS: The incidence rate (per one year) of thyroid cancer was 2.20 per 100,000 persons between 2004 and 2010 in Iran. Papillary thyroid cancer was the most common histology type, with an annual rate of 0.29 in Iran. The highest rate of prevalence in thyroid cancer was observed at the age of 45 years at the time of diagnosis. We found a female-to-male ratio of 2 in Iran. A significant decrease was detected in the trend of thyroid cancer in children <19y, which was not correlated to the trend of older patients. CONCLUSIONS: As expected, the trend of thyroid cancer increased over the 7 years, primarily contributed by papillary thyroid cancer. A rising pattern of incidence was seen in all the age groups except patients aged under 19 years. PMID- 26838248 TI - Safety and Efficacy of a Mouth-Rinse with Granulocyte Colony Stimulating Factor in Patients with Chemotherapy-Induced Oral Mucositis. AB - OBJECTIVE: To assess the safety and effectiveness of a mouth-rinse with G-CSF (JiSaiXin, produced by NCPC Biotechnology Co., Ltd) in treating patients with chemotherapy-induced oral mucositis (CIM). METHOD: A consecutive cohort of patients with advanced cancers and CIM were treated with mouth-rinse G-CSF. All chemotherapy for patients with advanced cancers was adopted from regimens suggested by NCCN guidelines. The mouth-rinse with G-CSF at a dose of 150-300ug plus 100ml-500ml normal saline was started from the time of oral mucositis was confirmed and continuously used for at least 7 days as one course. After at least two courses of treatment, safety and efficacy were evaluated. RESULTS: There were 7 female and 7 male patients with advanced cancer and CIM recruited into this study, including 5 with colorectal, 2 with lung, 1 patient with gastric, 1 with cervical and 1 with pancreatic cancer, as well as 2 patients with diffuse large B cell lymphomas, 1 with nasopharyngeal and 1 with gastric cancer. The median age was 57 (41-79) years. Grade 1 to 2 myelosuppression was observed in 3/14 patients, and Grade 4 myelosuppression in 1/14. Adverse effects on the gastrointestinal tract were documented in 5/14 patients, and were Grade 1 to Grade 3. No treatment related death was documented. Regarding CIM, the median response time to mouth rinse of G-CSF was 2 (1-5) days, and all patients with CIM demonstrated a positive response. CONCLUSIONS: Mouth-rinse with G-CSF proved to be safe and effective in treating patients with advanced cancers and CIM. However, further randomized controlled studies should be conducted to clarify the effectiveness of this treatment with other lesions. PMID- 26838249 TI - Correlation Between Nitrogen Dioxide as an Air Pollution Indicator and Breast Cancer: a Systematic Review and Meta- Analysis. AB - BACKGROUND: The aim of this systematic review was to study the relationship between exposure to nitrogen dioxide (NO2) in the ambient air and breast cancer incidence. MATERIALS AND METHODS: A systematic review was performed based on the MOOSE guideline for review of observational studies. We searched five online databases (PubMed, Science Direct, Google Scholar, EBSCO, and Scopus) from their conception to June 2014. A pooled estimate of the correlation between NO2 exposure and breast cancer incidence was calculated using Pearson's correlation coefficient. RESULTS: A total of 654 titles were retrieved in the initial search of the databases. Further refinement and screening of the retrieved studies produced a total of five studies from four countries. The studies included three ecological studies (aggregate level) and two individual based studies (one prospective cohort and the other one a case-control study). The ecological studies were pooled and the meta-analysis of correlation coefficient without z transformation showed a pooled estimate of r = 0.89 with 95% CI of 0.84 to 0.95. Using z transformation, the pooled r was 1.38 with 95%CI of 1.11 to 1.59. No significant heterogeneity between studies was observed. Following a sensitivity analysis and the removal of each study from pooled analysis we did not see any significant change in the pooled estimate. CONCLUSIONS: It was concluded that there is a tendency toward a weak association between exposure to NO2 in ambient air and breast cancer at the individual level and a significant association at the aggregate level. PMID- 26838250 TI - Comparative Study of Dermatoscopic and Histopathologic Results in Facial Basal Cell Carcinoma and Melanocytic Nevi. AB - BACKGROUND: Dermatoscopy can be applied to diagnose pigmented skin lesions. The aim of the present study was to compare dermatoscopic and histopathologic results in basal cell carcinoma (BCC) and melanocytic nevus of theface. MATERIALS AND METHODS: In an analytical-descriptive study, 61 patients suspected of BCC or melanocytic nevi of face were randomly selected. The skin lesions of patients were evaluated with dermatoscopic method from February 2012 to February 2014 and results were compared with pathological features of samples. RESULTS: In this study, mean age of patients was 49.5+/-18.9. Some 25 (41%) were men and 36 (59%) were women. In 27 cases (44.3%) there was diagnosis of melanocytic nevus, in 28 cases (45.9%) diagnosis of BCC, and in 3 cases (4.9%) there was mixed diagnosis. The relationship between patients' gender and dermatoscopic diagnosis of the patients was statistically significant (P=0.001). For BCC the sensitivity and specificity of dermatoscopic method were 100% and 97% respectively and for melanocytic nevi 96.4% and 97%. CONCLUSIONS: Dermatoscopic study not only can be helpful in improving clinical diagnosis while guiding missed malignant lesions to pathologic evaluations, but also could be useful in evaluating further suspicious or recurrent cases. PMID- 26838252 TI - Impact of an Information Leaflet on Knowledge of Hepatocellular Carcinoma and Hepatitis B among Chinese Youth. AB - BACKGROUND: To assess the effect of an information leaflet on the level of Chinese youth's knowledge about hepatitis B and hepatocellular carcinoma (HCC), the most common type of primary liver cancer (PLC). MATERIALS AND METHODS: A total of 500 students, from two universities in the Chaoshan area of China, were randomly divided into an intervention group of 280 participants and a control group of 220. Baseline knowledge of HCC and hepatitis B was evaluated by questionnaire interview. Subsequently, only the intervention group was given an information leaflet of HCC and hepatitis B. Three months later, the two groups were contacted for a second interview. Changes in knowledge from baseline of HCC and hepatitis B were compared between the two groups. RESULTS: There was no statistically significant difference in mean PRE-questionnaire scores between the intervention and control groups. However, the mean POST-questionnaire score was significantly higher in the intervention group after the intervention. The leaflet had the greatest effect on the participants' questionnaire score, and raised their level of knowledge about HCC and hepatitis B. CONCLUSIONS: The information leaflet intervention is significantly effective in improving the knowledge of HCC and hepatitis B among the youth. PMID- 26838251 TI - Impact of Global and Gene-Specific DNA Methylation in de Novo or Relapsed Acute Myeloid Leukemia Patients Treated with Decitabine. AB - In this investigation, global DNA methylation patterns and the specific methylation status of 5 genes were studied in DNA from peripheral blood (PB) and impact on progression free survival (PFS) and overall-survival (OS) in patients with de novo or relapsed acute myeloid leukemia (AML) treated with decitabine based regimens waas assessed. DNA was isolated from PB samples at the time of -1, 1, and 7 days of chemotherapy. Global methylation was determined by ELISA, and the CpG island DNA methylation profile of 5 genes using a DNA methylation PCR system. Our data demonstrated that patients with a high level of 5-mC had a poor prognosis after demethylation therapy and those who have low levels of 5-mC in PB achieved higher CR and better SO, but there was no significant correlation found between the 5-mC levels and other clinical features before treatment except the disease status. Higher methylation status of Sox2 and Oct4 genes was associated with differential response to demethylation therapy. A relatively low methylation percentage in one or both of these two genes was also associated with longer OS after decitabine based chemotherapy. We also suggest that global DNA and Oct 4/Sox2 methylation might impact on the pathogenesis of leukemia and play an important role in the initiation and progression. Moreover, dynamic analysis of 5 mC and Oct-4/Sox2 in peripheral blood nucleated cells of leukemia patients may provide clues to important molecular diagnostic and prognostic targets. PMID- 26838253 TI - Predictors of Cigarette Smoking among Young Adults in Mangalore, India. AB - BACKGROUND: The tobacco epidemic is a heralding health menace, particularly among college students. Tobacco usage among young can have an especially devastating effect as they can be exposed for longer periods. Data to estimate the prevalence of tobacco use in young adults will be a valuable addition to the existing resources. MATERIALS AND METHODS: An analytical cross-sectional study was therefore carried out in Mangalore city using a pre-tested, self-administered questionnaire adapted from the Global Youth Tobacco Survey (GYTS) with a representative sample of 720 students aged 18-20 years selected from degree colleges by multi-stage random sampling. RESULTS: Prevalence of 'ever users' and 'current users' of smoking were 20.4% and 11.4%, respectively. The mean age at initiation of cigarette smoking was 16 years and the majority (31 %) smoked in public places. Interestingly, 84% of them knew about the harmful effects of cigarette smoking. About one half of smokers had some or most of their friends smoking. Multivariate analysis revealed gender (OR=8.585: CI-3.26-22.5), pocket money (OR=4.165; CI=1.76-9.82) and peer's smoking habit (OR= 5.15; CI-2.21-11.9) have higher odds as correlates of tobacco usage among college students. CONCLUSIONS: It is of prime importance to highlight the role of prevention of smoking initiation rather than subsequently trying to stop the habit. Comprehensive interventions embracing family, friends and social milieu are needed to reduce tobacco use among students in India. PMID- 26838254 TI - Reversal of Multidrug Resistance in Mouse Lymphoma Cells by Extracts and Flavonoids from Pistacia integerrima. AB - Phytochemical investigation of Pistacia integerrima has highlighted isolation of two known compounds naringenin (1) and dihydrokaempferol (2). A crude extract and these isolated compounds were here evaluated for their effects on reversion of multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). The multidrug resistance P-glycoprotein is a target for chemotherapeutic drugs from cancer cells. In the present study rhodamine- 123 exclusion screening test on human mdr1 gene transfected mouse gene transfected L5178 and L5178Y mouse T-cell lymphoma cells showed excellent MDR reversing effects in a dose dependent manner. In silico molecular docking investigations demonstrated a common binding site for Rhodamine123, and compounds naringenin and dihydrokaempferol. Our results showed that the relative docking energies estimated by docking softwares were in satisfactory correlation with the experimental activities. Preliminary interaction profile of P-gp docked complexes were also analysed in order to understand the nature of binding modes of these compounds. Our computational investigation suggested that the compounds interactions with the hydrophobic pocket of P-gp are mainly related to the inhibitory activity. Moreover this study s a platform for the discovery of novel natural compounds from herbal origin, as inhibitor molecules against the P-glycoprotein for the treatment of cancer. PMID- 26838255 TI - CYP1A1 MspI Polymorphism and Cervical Carcinoma Risk in the Multi-Ethnic Population of Malaysia: a Case-Control Study. AB - BACKGROUND: Tobacco smoking is considered a risk factor for cervical cancer development due to the presence of tobacco based carcinogenic metabolites in cervical cells of female smokers. In this study, we investigated the role of the T3801C (MspI) polymorphism of CYP1A1, a gene encoding an enzyme necessary for the initiation of tobacco based carcinogen metabolism, on cervical cancer risk. The T to C substitution may alter CYP1A1 activities, potentially elevating cervical cancer risk. Since results of gene-disease association studies vary according to the study population, the multi-ethnic population of Malaysia provides an excellent representative cohort for identifying and comparing the cervical cancer risk among the 3 major ethnics in Southeast Asia in relation to CYP1A1 MspI polymorphism. MATERIALS AND METHODS: A total of 195 Thin Prep Pap smear samples from HPV negative and cancer free females were randomly selected as controls while 106 formalin fixed paraffin embedded samples from females with invasive cervical cancer were randomly selected for the cases group. The polymorphisms were identified using restriction fragment length polymorphism (RFLP) PCR. RESULTS: We found no significant associations between CYP1A1 MspI polymorphism and cervical cancer in the general Malaysian female population. However, upon ethnic stratification, the variant C/C genotype was significantly associated with a 4.66-fold increase in cervical cancer risk in Malay females (95% CI= 1.21-17.9; p=0.03). No significant association was observed in the Chinese and Indian females. Additionally, there were no significant associations in the dominant model and allele frequency model analysis in both the general and ethnically stratified female population of Malaysia. CONCLUSIONS: Our findings suggest that the C/C genotype of CYP1A1 MspI polymorphism is associated with the development of cervical carcinoma in the Malay females of Malaysia. PMID- 26838256 TI - Bioimpedence to Assess Breast Density as a Risk Factor for Breast Cancer in Adult Women and Adolescent Girls. AB - Although high mammographic density is one of the strongest predictors of breast cancer risk, X-ray based mammography cannot be performed before the recommended screening age, especially not in adolescents and young women. Therefore, new techniques for breast density measurement are of interest. In this pilot study in Guam and Hawaii, we evaluated a radiation-free, bioimpedance device called Electrical Breast DensitometerTM (EBD; senoSENSE Medical Systems, Inc., Ontario, Canada) for measuring breast density in 95 women aged 31-82 years and 41 girls aged 8-18 years. Percent density (PD) was estimated in the women's most recent mammogram using a computer-assisted method. Correlation coefficients and linear regression were applied for statistical analysis. In adult women, mean EBD and PD values of the left and right breasts were 230+/-52 and 226+/-50 Omega and 23.7+/ 15.1 and 24.2+/-15.2%, respectively. The EBD measurements were inversely correlated with PD (rSpearman=-0.52, p<0.0001); the correlation was stronger in Caucasians (rSpearman=-0.70, p<0.0001) than Asians (rSpearman=-0.54, p<0.01) and Native Hawaiian/Chamorro/Pacific Islanders (rSpearman=-0.34, p=0.06). Using 4 categories of PD (<10, 10-25, 26-50, 51-75%), the respective mean EBD values were 256+/-32, 249+/-41, 202+/-46, and 178+/-43 Omega (p<0.0001). In girls, the mean EBD values in the left and right breast were 148+/-40 and 155+/-54 Omega; EBD values decreased from Tanner stages 1 to 4 (204+/-14, 154+/-79, 136+/-43, and 119+/-16 Omega for stages 1-4, respectively) but were higher at Tanner stage 5 (165+/-30 Omega). With further development, this bioimpedance method may allow for investigations of breast development among adolescent, as well as assessment of breast cancer risk early in life and in populations without access to mammography. PMID- 26838257 TI - Anti-proliferative and Apoptotic Effects of Basella rubra (L.) Against 1, 2 Dimethyl Hydrazine-induced Colon Carcinogenesis in Rats. AB - Colorectal cancer is a very prevalent diagnosed cancer. The current study was performed in order to examine the role of BRAE (Basella rubra aqueous extract) in regulating aberrant crypt foci (ACF) formation, cell proliferation and inhibition of apoptosis in a colon carcinogenesis model in male Wistar rats. Rats were randomly allocated into six groups. Group I served as control, and group II acted as a drug control administered BRAE (250mg/kg b.w.) orally for 30 weeks. Rats in group III-VI were given subcutaneous injections of DMH (25mg/kg b.w. weekly) for 15 weeks to initiate colon carcinogenesis. Those in group IV and VI were administered BRAE along with DMH injections. Rats in group V were administered with BRAE after cessation of DMH injection. After 30 weeks of experimental period colons were obtained from experimental groups and analyzed for ACF incidence, argyrophilic nucleolar organizing region- associated proteins (AgNOR) count, histopathological and immunohistochemical changes. Only in DMH exposed groups were ACF and AgNOR numbers increased. Administration of BRAE appreciably decreased the numbers of ACF and AgNOR in BRAE treated groups. Histopathological findings revealed a high level of dysplastic changes with decreased number of goblet cells found only in only DMH injected rats. Administration of BRAE in treated group rats reversed these changes. Expression markers for cell proliferation (PCNA and Ki67) were elevated in DMH treated rats, but reduced with BRAE treatement. This expression was reversed with apoptosis markers (p53 and Caspase-3). Thus the results results of the present study were found to be significant and confirmed the potential efficacy of BRAE against colon carcinogenesis. PMID- 26838258 TI - Evaluation of the Histo-Epidemiological Profile of Solid Childhood Cancers in Togo. AB - BACKGROUND: Cancer is a subject of continuing concern, more common in adults than in children, but often with a poor outcome in the latter. Our study set itself the objective to describe the epidemiological and histological aspects of solid cancers in children in Togo. MATERIALS AND METHODS: This descriptive, cross sectional study focused on cases of solid cancers in children diagnosed from 2010 to 2014 (5 years) at the pathology laboratory of the Tokoin teaching hospital. Data were collected from the records of that laboratory. RESULTS: We collected 66 cases of childhood cancer representing 5% of all solid cancers. The annual incidence was 13.2 cases. The sex ratio (M/F) was 1.4; mean age was of 7.2+/-1.6 years. The age group most affected was that of 5-9 years (40.9%). Four histological groups of solid childhood cancers were listed: lymphoma (n=34 cases; 51.5%), embryonic cancer (n=17 cases; 25.8%), sarcomas (n=13 cases; 19.7%) and carcinoma (n=2 cases; 3%). The most common histological types were Burkitt lymphoma (36.4%), nephroblastoma (10.6%) and retinoblastoma (10.6%). CONCLUSIONS: This study shows that solid cancers in children are relatively frequent in Togo with a male predominance. They are still largely dominated by Burkitt lymphoma, followed by retinoblastoma and nephroblastoma. PMID- 26838260 TI - Impact of Time Interval Between Chemoradiation and Surgery on Pathological Complete Response and Survival in Rectal Cancer. AB - BACKGROUND: Limited data are available regarding the impact of time duration between chemoradiation (CRT) and surgery on pathological complete response (PCR). A PCR translates into better overall and disease free survival. The objective of this study was to determine effect of time duration on outcome after preoperative CRT in rectal cancer. MATERIALS AND METHODS: A retrospective review of patients undergoing operations for rectal adenocarcinoma between January 2005 and December 2010 was performed. Patients were divided in two groups: Group 1 underwent surgery in <= 8weeks post neoadjuvant CRT and Group 2 after 8 weeks. Patient characteristics, surgical procedure, histopathological details and number of loco regional and distant failures were compared. Expected 5 year overall survival and disease free survival was calculated using Kaplan Meier curves and significance was determined using the log rank test. RESULTS: There were 66 patients in group 1 and 93 in group 2. No significant difference in PCR was observed between the two. However, estimated 5 year DFS was significantly higher in Group 1 (66.7%) as compared to Group 2 (53.8%) (P=0.04). Estimated overall 5 year overall survival was not significantly different at 68.2% versus 54.3% (P= 0.09). CONCLUSIONS: Delaying surgery more than 8 weeks after preoperative CRT does not impact for PCR in rectal cancer. PMID- 26838259 TI - Knowledge, Attitude, and Practice Regarding Cervical Cancer among Rural Community Women in Northeast Thailand. AB - BACKGROUND: Cervical cancer is the second most common malignancy among women worldwide, and women of reproductive age in Thailand. However, information on the behavior regarding cervical cancer in rural community Thailand is sparse. OBJECTIVE: To assess the knowledge, attitude, and practice regarding cervical cancer (CC) among rural community women in Nakhon Ratchasima, Thailand, using predesigned structured questionnaires. MATERIALS AND METHODS: A cross-sectional survey was conducted in 8 villages of Non Sung district, Nakhon Ratchasima province, Thailand, during January to April 2015. Bloom's taxonomy was used as a framework for the study. 265 women aged between 30-60 years old were selected by simple random sampling. All participants completed predesigned questionnaires with 4 parts: demographic data, knowledge, attitude, and practice regarding cervical cancer. Descriptive statistics were used for analysis in this study. RESULTS: The majority of participants were in the age group of 41-50 years old (42.6%) with senior secondary school level of education (32.1%), marriage status (85.0%), agricultural employment (59.6%), and family income between 6,000- 10,000 baht per month (54.3%). Some 63.4% and 68.7% participants had high knowledge and moderate level of attitudes regarding CC, while 41.1%, 48.7%, and 10.2% had neem regularly, irregularly or never screened for CC, respectively. The main reasons for not screening were were shyness (44.4%) and no time (55.6%). Vaginal discharge and itching were the common signs and symptoms of participants who were screened at a health promotion hospital of sub-district. CONCLUSIONS: CC is still a health problem in the rural community. Therefore, health education is required, particularly for those who have never undergone screening. PMID- 26838261 TI - Bayesian Survival Analysis of High-Dimensional Microarray Data for Mantle Cell Lymphoma Patients. AB - BACKGROUND: Survival time of lymphoma patients can be estimated with the help of microarray technology. In this study, with the use of iterative Bayesian Model Averaging (BMA) method, survival time of Mantle Cell Lymphoma patients (MCL) was estimated and in reference to the findings, patients were divided into two high- risk and low-risk groups. MATERIALS AND METHODS: In this study, gene expression data of MCL patients were used in order to select a subset of genes for survival analysis with microarray data, using the iterative BMA method. To evaluate the performance of the method, patients were divided into high-risk and low-risk based on their scores. Performance prediction was investigated using the log-rank test. The bioconductor package "iterativeBMAsurv" was applied with R statistical software for classification and survival analysis. RESULTS: In this study, 25 genes associated with survival for MCL patients were identified across 132 selected models. The maximum likelihood estimate coefficients of the selected genes and the posterior probabilities of the selected models were obtained from training data. Using this method, patients could be separated into high-risk and low-risk groups with high significance (p<0.001). CONCLUSIONS: The iterative BMA algorithm has high precision and ability for survival analysis. This method is capable of identifying a few predictive variables associated with survival, among many variables in a set of microarray data. Therefore, it can be used as a low cost diagnostic tool in clinical research. PMID- 26838262 TI - Molecular mechanisms of bone formation in spondyloarthritis. AB - Spondyloarthritis comprise a group of inflammatory rheumatic diseases characterized by its association to HLA-B27 and the presence of arthritis and enthesitis. The pathogenesis involves both an inflammatory process and new bone formation, which eventually lead to ankylosis of the spine. To date, the intrinsic mechanisms of the pathogenic process have not been fully elucidated, and our progress is remarkable in the identification of therapeutic targets to achieve the control of the inflammatory process, yet our ability to inhibit the excessive bone formation is still insufficient. The study of new bone formation in spondyloarthritis has been mostly conducted in animal models of the disease and only few experiments have been done using human biopsies. The deregulation and overexpression of molecules involved in the osteogenesis process have been observed in bone cells, mesenchymal cells, and fibroblasts. The signaling associated to the excessive bone formation is congruent with those involved in the physiological processes of bone remodeling. Bone morphogenetic proteins and Wnt pathways have been found deregulated in this disease; however, the cause for uncontrolled stimulation remains unknown. Mechanical stress appears to play an important role in the pathological osteogenesis process; nevertheless, the association of other important factors, such as the presence of HLA-B27 and environmental factors, remains uncertain. The present review summarizes the experimental findings that describe the signaling pathways involved in the new bone formation process in spondyloarthritis in animal models and in human biopsies. The role of mechanical stress as the trigger of these pathways is also reviewed. PMID- 26838263 TI - Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer's Disease (AD). PMID- 26838264 TI - Characterization of Two-Pore Channel 2 by Nuclear Membrane Electrophysiology. AB - Lysosomal calcium (Ca(2+)) release mediated by NAADP triggers signalling cascades that regulate many cellular processes. The identification of two-pore channel 2 (TPC2) as the NAADP receptor advances our understanding of lysosomal Ca(2+) signalling, yet the lysosome is not amenable to traditional patch-clamp electrophysiology. Previous attempts to record TPC2 single-channel activity put TPC2 outside its native environment, which not reflect TPC2's true physiological properties. To test the feasibility of using nuclear membrane electrophysiology for TPC2 channel characterization, we constructed a stable human TPC2-expressing DT40TKO cell line that lacks endogenous InsP3R and RyR (DT40TKO-hTPC2). Immunostaining revealed hTPC2 expression on the ER and nuclear envelope. Intracellular dialysis of NAADP into Fura-2-loaded DT40TKO-hTPC2 cells elicited cytosolic Ca(2+) transients, suggesting that hTPC2 was functionally active. Using nuclear membrane electrophysiology, we detected a ~220 pS single-channel current activated by NAADP with K(+) as the permeant ion. The detected single-channel recordings displayed a linear current-voltage relationship, were sensitive to Ned 19 inhibition, were biphasically regulated by NAADP concentration, and regulated by PKA phosphorylation. In summary, we developed a cell model for the characterization of the TPC2 channel and the nuclear membrane patch-clamp technique provided an alternative approach to rigorously investigate the electrophysiological properties of TPC2 with minimal manipulation. PMID- 26838265 TI - Functional neuroimaging in obesity and the potential for development of novel treatments. AB - Recently, exciting progress has been made in understanding the role of the CNS in controlling eating behaviour and in the development of overeating. Regions and networks of the human brain involved in eating behaviour and appetite control have been identified with neuroimaging techniques such as functional MRI, PET, electroencephalography, and magnetoencephalography. Hormones that regulate our drive to eat (eg, leptin, insulin, and glucagon-like peptide-1) can affect brain function. Defects in central hunger signalling are present in many pathologies. On the basis of an understanding of brain mechanisms that lead to overeating, powerful neuroimaging protocols could be a future clinical approach to allow individually tailored treatment options for patients with obesity. The aim of our Review is to provide an overview of neuroimaging approaches for obesity (ie, neuroimaging study design, questions which can be answered by neuroimaging, and limitations of neuroimaging techniques), examine current models of central nervous processes regulating eating behaviour, summarise and review important neuroimaging studies investigating therapeutic approaches to treat obesity or to control eating behaviour, and to provide a perspective on how neuroimaging might lead to new therapeutic approaches to obesity. PMID- 26838267 TI - Processing of ferulic acid modified hemoglobin. AB - The application of hemoglobin-based oxygen carriers (HBOCs) remains stagnant because a large number of reactive oxygen species (ROS) will be produced in organisms when HBOCs are used. Ferulic acid (FA) has a known effect on quenching oxygen free radicals and relieving vasospasm. Thus a kind of FA modified hemoglobin (BAEGF-Hb) is expected to produce the anti-oxidation effect on HBOCs spontaneously, and reduce toxicity. Isoelectric focusing electrophoresis, UV-vis wavelength scanning, and oxygen affinity curve showed that hemoglobin (Hb) was successfully modified and this modification had no effect on the structure of Hb and P50. The modification degree of Hb is 4. PMID- 26838268 TI - NHS figures indicate variation in readmission rate among patients discharged at weekends. PMID- 26838266 TI - PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications. AB - Protein kinase R (PKR) has previously been suggested to mediate many of the deleterious consequences of a high-fat diet (HFD). However, previous studies have observed substantial phenotypic variability when examining the metabolic consequences of PKR deletion. Accordingly, herein, we have re-examined the role of PKR in the development of obesity and its associated metabolic complications in vivo as well as its putative lipid-sensing role in vitro. Here we show that the deletion of PKR does not affect HFD-induced obesity, hepatic steatosis or glucose metabolism, and only modestly affects adipose tissue inflammation. Treatment with the saturated fatty acid palmitate in vitro induced comparable levels of inflammation in WT and PKR KO macrophages, demonstrating that PKR is not necessary for the sensing of pro-inflammatory lipids. These results challenge the proposed role for PKR in obesity, its associated metabolic complications and its role in lipid-induced inflammation. PMID- 26838269 TI - Xeno-Free Extraction, Culture, and Cryopreservation of Human Adipose-Derived Mesenchymal Stem Cells. AB - Molecules of animal or bacterial origin, which pose a risk for zoonoses or immune rejection, are commonly used for extraction, culture, and cryopreservation of mesenchymal stem cells. There is no sequential and orderly protocol for producing human adipose-derived stem cells (hASCs) under xeno-free conditions. After standardizing a human platelet lysate (hPL) production protocol, four human adipose tissue samples were processed through explants with fetal bovine serum (FBS)-supplemented or hPL-supplemented media for extracting the adipose-derived stem cells. The cells were cultivated in cell culture medium + hPL (5%) or FBS (10%). The cellular replication rate, immunophenotype, and differentiation potential were evaluated at fourth passage. Cellular viability was evaluated before and after cryopreservation of the cells, with an hPL-based solution compared with an FBS-based solution. The explants cultured in hPL-supplemented media showed earlier and faster hASC proliferation than did those supplemented with FBS. Likewise, cells grown in hPL-supplemented media showed a greater proliferation rate, without losing the immunophenotype. Osteogenic differentiation of xeno-free hASC was higher than the hASC produced in standard conditions. However, adipogenic differentiation was reduced in xeno-free hASC. Finally, the cells cryopreserved in an hPL-based solution showed a higher cellular viability than the cells cryopreserved in an FBS-based. In conclusion, we have developed a complete xeno-free protocol for extracting, culturing, and cryopreserving hASCs that can be safely implemented in clinical studies. PMID- 26838270 TI - Comparative Analysis of Media and Supplements on Initiation and Expansion of Adipose-Derived Stem Cells. AB - Adipose-derived stem cells (ASCs) are being tested in clinical trials related to cell-based regenerative therapies. Although most of the current expansion protocols for ASCs use fetal calf serum (FCS), xenogeneic-free medium supplements are greatly desired. This study aims to compare the effect of FCS, human platelet lysate (hPL), and a fully defined medium on the initiation and maintenance of ASC cultures. ASCs obtained from five donors were cultured in five different media: StemPro, Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% hPL, or alpha-minimum essential medium (A-MEM) supplemented with 5% hPL, 10% hPL, or 10% FCS. The effect of media on proliferation, colony-forming units (CFUs), attachment, and morphology was assessed along with cell size, granularity, and immunophenotype. StemPro greatly compromised the initiation of ASC cultures, which could not survive more than a few passages. Cells cultured in A-MEM proliferated at a faster rate than in DMEM, and hPL significantly enhanced cell size, granularity, and proliferation compared with FCS. All media except StemPro supported CFUs equally well. Analysis of surface markers revealed higher levels of CD73 and CD105 in FCS-cultured ASCs, whereas increased levels of CD146 were found in hPL-cultured cells. Multiparametric flow cytometric analysis performed after seven passages revealed the existence of four distinct ASC subpopulations, all positive for CD73, CD90, and CD105, which mainly differed by their expression of CD146 and CD271. Analysis of the different subpopulations might represent an important biological measure when assessing different medium formulations for a particular clinical application. PMID- 26838272 TI - Indium- and Platinum-Free Counter Electrode for Green Mesoscopic Photovoltaics through Graphene Electrode and Graphene Composite Catalysts: Interfacial Compatibility. AB - The scarcity and noble indium and platinum (Pt) are important elements in photoelectric nanomaterials. Therefore, development of low cost alternative materials to meet different practical applications is an urgent need. Two dimensional (2D) layered graphene (GE) with unique physical, mechanical, and electrical properties has recently drawn a great deal of attention in various optoelectronic fields. Herein, the large scale (21 cm * 15 cm) high-quality single layer graphene (SLG) and multilayer graphene on a flexible plastic substrate PET were controllably prepared through layer-by-layer (LBL) transfer using the thermal release adhesive transfer method (TRA-TM). Transmission and antibending performance based on PET/GE were superior to traditional PET/ITO. The square resistance of a nine-layer graphene electrode reached approximately 58 Omega. Combined with our newly developed and highly effective Fe3O4@RGO (reduced graphene oxide) catalyst, the power conversion efficiency of the dye-sensitized solar cell (DSC) using flexible PET/GE conductive substrate was comparable to that of the DSC using the PET/ITO substrate. The desirable performance of PET/GE/Fe3O4@RGO counter electrodes (low-cost indium- and platinum-free counter electrodes) is attributed to the interfacial compatibility between 2D graphene composite catalyst (Fe3O4@RGO) and 2D PET/GE conductive substrate. In addition, DSCs that use only PET/GE (without Fe3O4@RGO catalyst) as counter electrodes can also achieve a photocurrent density of 6.30 mA cm(-2). This work is beneficial for fundamental research and practical applications of graphene and graphene composite in photovoltaics, photocatalytic water splitting, supercapacitors. PMID- 26838271 TI - A Study of Human Leukocyte Antigen Mismatched Cellular Therapy (Stem Cell Microtransplantation) in High-Risk Myelodysplastic Syndrome or Transformed Acute Myelogenous Leukemia. AB - The treatment outcomes of myelodysplastic syndrome (MDS) and transformed acute myelogenous leukemia (tAML) remain very unsatisfactory. We designed a combination of human leukocyte antigen (HLA)-mismatched hematopoietic stem cell microtransplantation (MST) with chemotherapy for patients with MDS and tAML and evaluated its effects and toxicity. Patients were between 13 and 79 years old. Patients with MDS (n=21) were given HLA-mismatched MST combined with decitabine and cytarabine; patients with tAML (n=22) were given HLA-mismatched MST combined with decitabine and cytarabine, and also mitoxantrone. Patients in complete remission (CR) also received MST plus decitabine and medium-dose cytarabine chemotherapy without graft-versus-host disease (GVHD) prophylaxis. The overall response rate of the patients with MDS was significantly higher than that of those with tAML (81% vs. 50%; p=.03). The CR rates were 52.4% and 36.4% in the two groups, respectively. There was no difference in the cytogenetic CR rate between the MDS and tAML groups (85.7% vs. 70%, respectively; p=.7). The 24-month overall survival of the patients with MDS was significantly higher than that of the patients with tAML (84.7% and 34.1%, respectively; p=.003). The median recovery times of neutrophils and platelets were, respectively, 14 and 17 days in the patients with MDS, and 16 and 19 days in those with tAML. The treatment related mortality rates were 4.8% and 18.2%, respectively, in the MDS and tAML groups (p=.34). No GVHD was observed in any patient. Microtransplantation combined with decitabine and chemotherapy may provide a novel, effective, and safe treatment for high-risk MDS and tAML. SIGNIFICANCE: Microtransplantation (MST) refers to regular chemotherapy combined with granulocyte colony-stimulating factor-mobilized peripheral blood stem cell infusion of human leukocyte antigen mismatched donor cells without using immunosuppressive agents. It aims to support hematopoietic recovery and perform graft-versus-leukemia (GVL) effects but differs from traditional allogeneic stem cell transplantation because the rate of donor cell chimerism is low and there is and no graft-versus-host disease (GVHD) risk. Thus, a trial was designed to evaluate the safety and efficacy of MST in patients with myelodysplastic syndrome and those with transformed acute myelogenous leukemia. Higher complete remission and cytogenetic complete response rates were observed, and the treatment improved disease progress-free survival, sped hematopoietic recovery, and avoided GVHD. PMID- 26838273 TI - Yes we can! Successful examples of disallowing 'conscientious objection' in reproductive health care. AB - Reproductive health care is the only field in medicine where health care professionals (HCPs) are allowed to limit a patient's access to a legal medical treatment - usually abortion or contraception - by citing their 'freedom of conscience.' However, the authors' position is that 'conscientious objection' ('CO') in reproductive health care should be called dishonourable disobedience because it violates medical ethics and the right to lawful health care, and should therefore be disallowed. Three countries - Sweden, Finland, and Iceland - do not generally permit HCPs in the public health care system to refuse to perform a legal medical service for reasons of 'CO' when the service is part of their professional duties. The purpose of investigating the laws and experiences of these countries was to show that disallowing 'CO' is workable and beneficial. It facilitates good access to reproductive health services because it reduces barriers and delays. Other benefits include the prioritisation of evidence-based medicine, rational arguments, and democratic laws over faith-based refusals. Most notably, disallowing 'CO' protects women's basic human rights, avoiding both discrimination and harms to health. Finally, holding HCPs accountable for their professional obligations to patients does not result in negative impacts. Almost all HCPs and medical students in Sweden, Finland, and Iceland who object to abortion or contraception are able to find work in another field of medicine. The key to successfully disallowing 'CO' is a country's strong prior acceptance of women's civil rights, including their right to health care. PMID- 26838274 TI - Assessment of central venous catheter colonization using surveillance culture of withdrawn connectors and insertion site skin. AB - BACKGROUND: Culture of catheter hubs and skin surrounding the catheter entry site has a negative predictive value for catheter tip colonization. However, manipulation of the hub for culture requires the hubs to be swabbed, introducing potential dislodging of biofilm and subsequent migration of microorganisms. Hubs are usually closed with needleless connectors (NCs), which are replaced regularly. Our objective was to evaluate whether culture of flushed withdrawn NCs is an alternative to hub culture when investigating central venous catheter colonization. METHODS: The study population comprised 49 intensive care unit patients whose central venous catheters had been in place for at least 7 days. Cultures of NCs and skin were obtained weekly. RESULTS: We included 82 catheters with more than 7 days' indwelling time. The catheter tip colonization rate was 18.3% (15/82). Analysis of skin and NC cultures revealed a 92.5% negative predictive value for catheter colonization. Three episodes of catheter-related bloodstream infection (C-RBSI) occurred in patients with colonized catheters. CONCLUSION: Surveillance of NC and skin cultures could help to identify patients at risk for C-RBSI. PMID- 26838275 TI - Comparison of Pharmacokinetics and Biodistribution of 10-Deacetylbaccatin III after Oral Administration as Pure Compound or in Taxus chinensis Extract: A Pilot Study. AB - Taxanes are a class of bioactive compounds isolated from the Taxus species. 10 Deacetylbaccatin III is one of the popular taxane compounds with antitumor activity, but the pharmacokinetic profile of this compound remains elusive. Previously, we prepared the taxane fractions from the twigs and leaves of Taxus chinensis var. mairei containing 20.4 % 10-deacetylbaccatin III. This study aimed to investigate the pharmacokinetics of 10-deacetylbaccatin III and biodistribution, and explore the potential changes when it was administered in the form of taxane extracts. A simple, sensitive, and reliable liquid chromatography-tandem mass spectrometry method was developed and validated for the quantitative determination of 10-deacetylbaccatin III in biosamples. The results showed that 10-deacetylbaccatin III, after oral dosing, displayed a quick absorption into the blood and distribution into major organs. Oral administration of 10-deacetylbaccatin III in the form of taxane mixtures led to a 16-fold increase in the systemic exposure of pure 10-deacetylbaccatin III, with the AUC0 U in the plasma increasing from 25.75 +/- 11.34 to 231.36 +/- 70.12 ug h/L (p < 0.0001). Moreover, the concentrations of 10-deacetylbaccatin III in major tissues were significantly enhanced when given in taxane extracts. These findings revealed pharmacokinetic interactions in the taxane components from T. chinensis var. mairei, which contributed to an enhanced systemic exposure of pharmacologically active taxanes. PMID- 26838279 TI - Less Common Variants and Mimics of DCIS. AB - The purpose of this review is to discuss the less common variants and mimics of ductal carcinoma in situ (DCIS). DCIS lesions are heterogeneous in clinical presentation and behavior, morphology, biomarker profile, and identified genetic aberrations. DCIS is most easily recognized when presenting with classical features. The diagnosis is more challenging when a lesion displays less common cytologic features and has architectural patterns that overlap with other benign or malignant entities. PMID- 26838280 TI - Invasive Lobular Carcinoma of the Breast. AB - Invasive lobular carcinoma of the breast is a distinct histologic type with specific clinical, radiologic, and microscopic features, which is increasing in incidence in the Western World. Routine pathologic prognostic factors, including grade, lymph node stage, and size are of significance in predicting outcome in this group of patients who, overall, have survival comparable to those with other subtypes of breast cancer. Variants, however, are seen and these, as well as other standard factors such as histologic grade, have prognostic significance and should be recorded in pathology reports. PMID- 26838281 TI - Important Inflammatory and Reactive Lesions of the Breast. AB - Some inflammatory and reactive lesions of the breast present problems clinically but are treated without resort to biopsy. In others, biopsy is required to make the correct diagnosis and to distinguish the process from malignancy. Still others represent incidental microscopic findings that may create diagnostic problems. This article reviews a number of inflammatory and reactive conditions that are likely to be encountered in routine surgical pathology practice, as well as those that have been recently described. PMID- 26838278 TI - Modeling cell shape and dynamics on micropatterns. AB - Adhesive micropatterns have become a standard tool to study cells under defined conditions. Applications range from controlling the differentiation and fate of single cells to guiding the collective migration of cell sheets. In long-term experiments, single cell normalization is challenged by cell division. For all of these setups, mathematical models predicting cell shape and dynamics can guide pattern design. Here we review recent advances in predicting and explaining cell shape, traction forces and dynamics on micropatterns. Starting with contour models as the simplest approach to explain concave cell shapes, we move on to network and continuum descriptions as examples for static models. To describe dynamic processes, cellular Potts, vertex and phase field models can be used. Different types of model are appropriate to address different biological questions and together, they provide a versatile tool box to predict cell behavior on micropatterns. PMID- 26838282 TI - Small Glandular Proliferations of the Breast. AB - This article discusses the most common small glandular proliferations, namely sclerosing lesions (sclerosing adenosis and radial scar), tubular carcinoma, and epithelial displacement after needle core biopsy, as well as less common entities, such as low-grade adenosquamous carcinoma, microglandular adenosis, and syringomatous adenoma. Due to significant morphologic overlap, these entities are easily mistaken for one another. The similarities and differences among these lesions in their clinicopathologic features, radiologic findings, and immunohistochemical profiles are emphasizesd. PMID- 26838283 TI - Vascular Lesions of the Breast. AB - Vascular lesions represent a minority of tumors originating in the breast. The most common entities are benign and include hemangiomas and angiolipomas. Malignant vascular lesions (angiosarcomas) are rare and may be primary or secondary to radiation. Also appreciated in association to radiotherapy is the development of cutaneous atypical vascular lesion affecting the skin of the breast. The relationship of the latter to radiation-associated angiosarcoma is controversial and remains to be elucidated. This article reviews the most likely encountered vascular lesions in the breast, with emphasis on key pathologic diagnostic features and potential diagnostic pitfalls. PMID- 26838284 TI - Combined Epithelial-Myoepithelial Lesions of the Breast. AB - Epithelial-myoepithelial proliferations of the breast are a heterogeneous poorly defined group of lesions characterized morphologically by dual differentiation into ductal (luminal) and myoepithelial cells. They include neoplastic and non neoplastic entities that have overlapping morphologic features that may give rise to diagnostic difficulty. Many of these entities are low grade or of uncertain malignant potential but the biology of some of these rare lesions remains to be elucidated. This article discusses the differential diagnosis of epithelial myoepithelial lesions of the breast and highlights the morphologic features of some of these entities. PMID- 26838285 TI - Molecular Classification of Breast Cancer. AB - This article reviews the conceptual and practical implications of the intrinsic subtype classification of breast cancers and the limitations of this approach. It presents the most extensively validated gene expression assays proposed as predictors of clinical outcome and discusses their potential clinical utility and limitations. PMID- 26838286 TI - Metastases to and from the Breast. AB - Breast cancer is a common source of systemic metastatic disease. Distinguishing metastatic breast cancer from other types of malignancies can be diagnostically challenging but is important for correct treatment and prognosis. Nonmammary tumors can also metastasize to the breast, although this is a rare phenomenon. Differentiating a metastasis to the breast from a primary breast cancer can likewise be difficult. Knowledge of the clinical history and careful morphologic evaluation are the cornerstones of diagnosis. A panel of immunohistochemical stains tailored to the differential diagnosis at hand can provide helpful information in ambiguous cases. PMID- 26838287 TI - Pathology Considerations in Patients Treated with Neoadjuvant Chemotherapy. AB - Neoadjuvant therapy (NAT) originally reserved for the treatment of inflammatory and locally advanced breast cancers is currently offered to women with earlier stage and operable breast carcinoma. NAT allows more women to be eligible for breast conservation surgery and provides an opportunity to assess the response of carcinomas to therapy. This review focuses on the predictors of therapeutic response in pretreatment tumor, evaluation of post-treatment breast and lymph node specimens and classification systems to evaluate degree of response to NAT. PMID- 26838288 TI - Prognostic Factors for Patients with Breast Cancer: Traditional and New. AB - At the time of breast cancer diagnosis, multiple features of the tumor are routinely assessed to evaluate for prognostic and predictive factors. Prognostic factors provide information about the patient's likely clinical course and include tumor stage (composed of lymph node status, tumor size, and presence of chest wall involvement), tumor histologic type and grade, estrogen and progesterone receptor expression, and HER2 status. These traditional prognostic factors are reviewed with particular attention to problematic areas in classification. Several newer prognostic tests may be able to provide information beyond the traditional prognostic factors and are presented. PMID- 26838289 TI - Breast Pathology: Diagnostic Dilemmas. PMID- 26838290 TI - Isomer differentiation through supramolecular self-assembly in microdroplets of milliseconds life-time. AB - Supramolecular recognition of thymine (or its analogs) with various central cations can form magic number clusters. Dual nano-ESI via theta tip emitters was used to on-line synthesize clusters. Even thermodynamically unstable clusters can be detected by MS thanks to the very short life-time (~ms) of the generated microdroplets. By recording characteristic cluster distributions, isomers can be clearly differentiated in a novel "bottom-up" way. Theoretical calculations were performed to explain the MS results. PMID- 26838291 TI - Attribution of Salmonella enterica serotype Hadar infections using antimicrobial resistance data from two points in the food supply system. AB - A challenge to the development of foodborne illness prevention measures is determining the sources of enteric illness. Microbial subtyping source attribution models attribute illnesses to various sources, requiring data characterizing bacterial isolate subtypes collected from human and food sources. We evaluated the use of antimicrobial resistance data on isolates of Salmonella enterica serotype Hadar, collected from ill humans, food animals, and from retail meats, in two microbial subtyping attribution models. We also compared model results when either antimicrobial resistance or pulsed-field gel electrophoresis (PFGE) patterns were used to subtype isolates. Depending on the subtyping model used, 68-96% of the human infections were attributed to meat and poultry food products. All models yielded similar outcomes, with 86% [95% confidence interval (CI) 80-91] to 91% (95% CI 88-96) of the attributable infections attributed to turkey, and 6% (95% CI 2-10) to 14% (95% CI 8-20) to chicken. Few illnesses (<3%) were attributed to cattle or swine. Results were similar whether the isolates were obtained from food animals during processing or from retail meat products. Our results support the view that microbial subtyping models are a flexible and robust approach for attributing Salmonella Hadar. PMID- 26838292 TI - Reductions of left ventricular mass and atrial size following renal denervation: a meta-analysis. AB - BACKGROUND: Renal denervation (RDN), a novel therapy for resistant hypertension, has been shown to have an effect on cardiac remodeling in several small studies. We aimed to pool currently available data to assess the effects of RDN on left ventricular hypertrophy (LVH) and left atrial (LA) enlargement. METHODS AND RESULTS: Two investigators independently searched PubMed, EMBASE and Cochrane Library Central Register of Controlled Trials database for studies reporting change in left ventricular mass index (LVMI) or LA size before and after RDN. Twelve publications met our pre-defined inclusion criteria. Echocardiographic data showed that RDN markedly reduced both LVMI [weighted mean difference (WMD) = -15.77 g/m(2); 95 % confidence interval (CI) -22.51 to -9.02 g/m(2)] and LA diameter [WMD = -2.48 mm; 95 % CI -4.12 to -0.83 mm] after 6 months. Data from cardiac magnetic resonance also showed a significant reduction in LVMI [WMD = 5.43 g/m(2), 95 % CI -10.01 to -0.35 g/m(2)) at 6 months. Changes in LVH and LA size at 12 months were more pronounced than those at 6 months. Meta-regression analysis failed to demonstrate a significant relationship between RDN-induced LVMI reduction and BP lowering at 6 months. CONCLUSIONS: RDN led to significant regressions of both LVH and LA enlargement at 6 months, which were sustained at least up to 12 months. PMID- 26838294 TI - Synthesis and characterization of large-area and continuous MoS2 atomic layers by RF magnetron sputtering. AB - In this article, we report layer-controlled, continuous and large-area molydenum sulfide (MoS2) growth onto a SiO2/Si substrate by RF sputtering combined with sulfurization. A two-step process was employed to synthesize MoS2 films. In the first step, an atomically thin MoO3 film was deposited by RF magnetron sputtering at 300 degrees C. Subsequently, the as-sputtered MoO3 film was further subjected to post-annealing and sulfurization processes at 650 degrees C for 1 hour. It was observed that the number of layers of MoS2 can be controlled by adjusting the sputtering time. The fabricated MoS2 transistors exhibited high mobility values of ~21 cm(2) V(-1) s(-1) (bilayer) and ~25 cm(2) V(-1) s(-1) (trilayer), on/off ratios in the range of ~10(7) (bilayer) and 10(4)-10(5) (trilayer), respectively. We believe that our proposed paradigm can start a new method for the growth of MoS2 in future electronics and optoelectronics applications. PMID- 26838293 TI - Watchful waiting as a treatment strategy for patients with a ventral hernia appears to be safe. AB - PURPOSE: Due to risks of postoperative morbidity and recurrence some patients with a ventral hernia are not offered surgical repair. There is limited data on the rate and consequences of a watchful waiting (WW) strategy for these patients. The objective of this cohort study was to analyse outcomes for patients with a ventral hernia who underwent watchful waiting, in terms of later requirement for hernia repair. METHODS: All patients (>=18 years) electively referred to our out patient clinic from 1 January 2009 to 1 July 2014 with incisional, umbilical or epigastric hernia were included. Information on patient characteristics and whether patients underwent WW or surgery was obtained from hospital files and the Danish National Patient Register. A 100% follow-up was obtained. RESULTS: The analyses comprised 569 patients with incisional hernia (WW = 58.1%) and 789 patients with umbilical/epigastric hernia (WW = 43.2%). Kaplan-Meier analyses estimated that the probability for patients who underwent watchful waiting to receive later surgical repair was 19 for incisional hernias and 16% for umbilical/epigastric hernias after 5 years. The probability of requiring emergency repair when in the WW group was 4% for both incisional and umbilical/epigastric hernias after 5 years. There were no significant differences in 30-day readmission, reoperation or mortality rates between the WW patients who later underwent elective hernia repair and patients who were initially offered surgery (p > 0.05), for both incisional and umbilical/epigastric hernias. CONCLUSIONS: Watchful waiting appears to be a safe strategy in the treatment of incisional, umbilical and epigastric hernias. PMID- 26838295 TI - Patient with giant upper limb melanoma presenting to a UK plastic surgery unit: differentials and experience of management. AB - A 57-year-old woman was referred to our regional sarcoma unit following a 2-year history of a progressively enlarging mass on her right forearm. At 14 * 7 * 12 cm, this mass turned out to be one of the largest upper limb cutaneous malignant melanomas ever described, and, to the best of our knowledge, the first documented in the UK. Remarkably, despite having a T4 malignant tumour with a Breslow thickness of 70 mm, this patient is still alive over 4 years later with no locoregional or distant metastatic spread. We present our experience in the management of this giant malignant melanoma of the upper limb and consider important differentials. PMID- 26838296 TI - Nocturnal seizure and simultaneous bilateral shoulder fracture-dislocation. AB - An otherwise fit and well 27-year-old man presented with acute onset unexplained bilateral shoulder pain, and was found to have bilateral shoulder fractures and dislocations on imaging. Although features were atypical, a nocturnal seizure causing the bilateral shoulder fractures was suspected and EEG showed features compatible with epilepsy. PMID- 26838297 TI - Urothelial carcinoma presenting with distant metastasis to the rectum. AB - Urothelial carcinomas (UC) arise from transitional cells in the urothelial tract. Advanced cases can spread locally to invade surrounding organs, or metastasise distantly to the lungs, bone or liver. We describe a case of an elderly woman with no previous cancer history, presenting with symptoms of an unusual distant metastasis. PMID- 26838298 TI - Hidden acral lentiginous melanoma with cutaneous metastases masquerading as Kaposi's sarcoma in an HIV-positive Indian man. AB - A 33-year-old HIV-positive Indian man presented with multiple bluish and erythematous papulo-nodules on his right leg and foot. A diagnosis of Kaposi's sarcoma was suspected clinically. Biopsy of the cutaneous lesions showed features of melanoma. On careful re-examination, an irregular brown-black macule, of which the patient was unaware, was noted on the ipsilateral sole. Histological examination of the sole lesion also showed features of melanoma. Systemic evaluation revealed extensive nodal and visceral metastases. PMID- 26838299 TI - Recovery from delirium and psychotic manifestations following treatment of anaemia with off-label rituximab in active cold haemagglutinin disease. AB - Anaemia is an independent, commonly under-recognised risk factor for delirium. Prompt management of anaemia and its underlying aetiology could result in recovery from delirium and associated psychotic manifestations. We report this unprecedented case of complete recovery from delirium and challenging behaviour, following treatment of autoimmune haemolytic anaemia with rituximab. PMID- 26838300 TI - Acute EBV masquerading as peripheral T-cell lymphoma. AB - Histological features of Epstein-Barr virus (EBV) can rarely mimic lymphoma. A 25 year-old presented with a spontaneous splenic rupture following a short illness. Histopathology assessment of the splenic and marrow tissue was highly suggestive of peripheral T-cell lymphoma not-otherwise-specified (PTCL-NOS). T-cell receptor (TCR) PCR clonality studies revealed a monoclonal T-cell population expressing for both TCRbeta and gamma, strongly suggestive of a T-cell clonal disease. EBV IgM was positive and IgG negative. EBV PCR was positive (7.02 *10(4)/mL). Despite the strong suggestion of PTCL-NOS from histopathology and clonality studies, the decision was made to observe the patient and not start multiagent chemotherapy. The patient remained well, with no signs of PTCL and subsequently seroconverted to IgG+ EBV. We highlight the potential pitfall of acute EBV masquerading as PTCL and show the critical role of the multidisciplinary integration of histopathological, serology, molecular and clinical features to avoid misdiagnosis. PMID- 26838301 TI - Vitamin D deficiency mimicking chronic tension-type headache in children. AB - Headache, musculoskeletal pain and vitamin D deficiency, with possible inter relationship, are common in the general population. We report cases of three premenarchal girls presenting with chronic tension-type headache and generalised body pain. The patients did not show any response to conventional therapy for tension headache. Investigations showed a severe vitamin D deficiency and biochemical osteomalacia in all three patients. The headaches and musculoskeletal pain responded markedly to vitamin D therapy. We suggest that musculoskeletal pain and headache together in a patient may be part of a single symptom complex, with vitamin D deficiency being the possible cause. PMID- 26838302 TI - Ruptured subcapsular liver haematoma following mechanically-assisted cardiopulmonary resuscitation. AB - A 64-year-old man with a history of ascending aortic surgery and pulmonary embolus presented with shortness of breath. He rapidly decompensated, prompting intubation, after which he lost pulses. Manual resuscitation was initiated immediately, with subsequent use of a LUCAS-2 mechanical compression device. The patient was given bolus thrombolytic therapy and regained pulses after 7 min of CPR. Compressions were reinitiated with the LUCAS-2 twice more during resuscitation over the subsequent hour for brief episodes of PEA. After confirmation of massive pulmonary embolism on CT, the patient underwent interventional radiology-guided ultrasonic catheter placement with local thrombolytic therapy and experienced immediate improvement in oxygenation. He later developed abdominal compartment syndrome, despite cessation of thrombolytic and anticoagulation therapy. Bedside exploratory abdominal laparotomy revealed a ruptured subcapsular haematoma of the liver. The patient's haemodynamics improved following surgery and he was extubated 11 days postarrest with intact neurological function. PMID- 26838303 TI - Process of determining the value of belief about jinn possession and whether or not they are a result of mental illness. AB - We present the case of a 28-year-old Afghan woman who presented perinatally with concerns of being possessed by jinns. She was noted to have third person auditory hallucinations, delusions of control and somatic passivity. She was diagnosed with schizophrenia and was treated with antipsychotic medications with a positive outcome. Her husband also believed that his wife was possessed and believed that her jinns talked through his wife on occasions. He did not experience any psychotic symptoms himself. In the Muslim faith, beliefs about jinns are widely held by people with and without any signs of mental illness. We feel that the patient's interpretation of her symptoms was influenced by her and her husband's religious and cultural beliefs, leading to a delay in receiving appropriate treatment. Awareness among mental health professionals about widely held religious and cultural beliefs will enhance the assessment, diagnosis and treatment of similar presentations. PMID- 26838304 TI - Iodide mumps following fistulogram in a haemodialysis patient. AB - Iodide mumps, or contrast-induced acute sialadenitis, is characterised by rapid, painless enlargement of the salivary glands, following the use of iodinated contrast dye. The underlying mechanism of this adverse reaction is not completely understood. It could be due to an idiosyncratic reaction or related to deposition of iodide in the ductal systems of the salivary glands causing blockage and inflammation. With increasing renal dysfunction, the elimination half-life of the iodine-containing contrast dye gets prolonged. The course of iodine-induced sialadenitis is usually benign, and rapid resolution of symptoms is expected without definite treatment. The symptomatic management includes treatment with a parenteral non-steroidal anti-inflammatory drug (NSAID), steroids and dialysis. However, the role of steroids has been found to be controversial in previously published case reports. Pancreatic mumps and transient thyroid dysfunction were also reported in patients following iodinated contrast administration; the aetiology of this is thought to be similar to iodide-induced sialadenitis. PMID- 26838305 TI - An unconventional therapeutic approach to a migratory IUD causing perforation of the rectum. AB - Intrauterine devices (IUDs) are a commonly used form of contraception. The risk of perforation and migration of these devices have been reported to be 1 in 1000. Migration into the rectum is even more uncommon. The following case illustrates a previously healthy 37-year-old woman who experienced a perforation and migration of an IUD into the rectum necessitating endoscopic removal. To our knowledge, this complication of IUD and subsequent endoscopic removal has not been previously described and presents a viable first-line therapeutic option in a stable patient. PMID- 26838307 TI - Junior doctors will take industrial action next week. PMID- 26838306 TI - Cold atmospheric plasma jet-generated RONS and their selective effects on normal and carcinoma cells. AB - Cold atmospheric helium plasma jets were fabricated and utilized for plasma-cell interactions. The effect of operating parameters and jet design on the generation of specific reactive oxygen and nitrogen species (RONS) within cells and cellular response were investigated. It was found that plasma treatment induced the overproduction of RONS in various cancer cell lines selectively. The plasma under a relatively low applied voltage induced the detachment of cells, a reduction in cell viability, and apoptosis, while the plasma under higher applied voltage led to cellular necrosis in our case. To determine whether plasma-induced reactive oxygen species (ROS) generation occurs through interfering with mitochondria related cellular response, we examined the plasma effects on ROS generation in both parental A549 cells and A549 rho(0) cells. It was observed that cancer cells were more susceptible to plasma-induced RONS (especially nitric oxide (NO) and nitrogen dioxide (NO2(-)) radicals) than normal cells, and consequently, plasma induced apoptotic cell responses mainly in cancer cells. PMID- 26838308 TI - From Single Myocyte to Whole Heart: The Intricate Dance of Electrophysiology and Modeling. PMID- 26838309 TI - (Pro)renin Receptor and LDL Clearance: An Old Player Joins A New Game. PMID- 26838310 TI - Deficient CDKN2B Expression: A Double Hit for PAD. PMID- 26838312 TI - Novel Insights Into the Mechanisms Regulating Pro-Atrial Natriuretic Peptide Cleavage in the Heart and Blood Pressure Regulation: Proprotein Convertase Subtilisin/Kexin 6 Is the Corin Activating Enzyme. PMID- 26838311 TI - The Relationship Between KLF5 and PPARalpha in the Heart: It's Complicated. PMID- 26838313 TI - Gerald W. Dorn II: Thinker, Teacher, Tinkerer. PMID- 26838314 TI - The Role of Exercise in Cardiac Aging: From Physiology to Molecular Mechanisms. AB - Aging induces structural and functional changes in the heart that are associated with increased risk of cardiovascular disease and impaired functional capacity in the elderly. Exercise is a diagnostic and therapeutic tool, with the potential to provide insights into clinical diagnosis and prognosis, as well as the molecular mechanisms by which aging influences cardiac physiology and function. In this review, we first provide an overview of how aging impacts the cardiac response to exercise, and the implications this has for functional capacity in older adults. We then review the underlying molecular mechanisms by which cardiac aging contributes to exercise intolerance, and conversely how exercise training can potentially modulate aging phenotypes in the heart. Finally, we highlight the potential use of these exercise models to complement models of disease in efforts to uncover new therapeutic targets to prevent or treat heart disease in the aging population. PMID- 26838318 TI - Mending a Faltering Heart. AB - More people die every year from ischemic heart disease than any other disease. Because the human heart lacks sufficient ability to replenish the damaged cardiac muscles, extensive research has been devoted toward understanding the homeostatic and regenerative potential of the heart and to develop regenerative therapies for heart disease. Here, we discuss recent advances in the understanding of mechanisms governing heart growth during homeostasis or injury, including those from observational studies in humans and experimental research in animal models of cardiac regeneration. We also discuss how progress in stem cell biology and cellular reprogramming has enabled exciting new strategies for cardiac regeneration. PMID- 26838315 TI - Mechanical Forces Reshape Differentiation Cues That Guide Cardiomyogenesis. AB - Soluble morphogen gradients have long been studied in the context of heart specification and patterning. However, recent data have begun to challenge the notion that long-standing in vivo observations are driven solely by these gradients alone. Evidence from multiple biological models, from stem cells to ex vivo biophysical assays, now supports a role for mechanical forces in not only modulating cell behavior but also inducing it de novo in a process termed mechanotransduction. Structural proteins that connect the cell to its niche, for example, integrins and cadherins, and that couple to other growth factor receptors, either directly or indirectly, seem to mediate these changes, although specific mechanistic details are still being elucidated. In this review, we summarize how the wingless (Wnt), transforming growth factor-beta, and bone morphogenetic protein signaling pathways affect cardiomyogenesis and then highlight the interplay between each pathway and mechanical forces. In addition, we will outline the role of integrins and cadherins during cardiac development. For each, we will describe how the interplay could change multiple processes during cardiomyogenesis, including the specification of undifferentiated cells, the establishment of heart patterns to accomplish tube and chamber formation, or the maturation of myocytes in the fully formed heart. PMID- 26838319 TI - RhoA/Rho-Kinase in the Cardiovascular System. AB - Twenty years ago, Rho-kinase was identified as an important downstream effector of the small GTP-binding protein, RhoA. Thereafter, a series of studies demonstrated the important roles of Rho-kinase in the cardiovascular system. The RhoA/Rho-kinase pathway is now widely known to play important roles in many cellular functions, including contraction, motility, proliferation, and apoptosis, and its excessive activity induces oxidative stress and promotes the development of cardiovascular diseases. Furthermore, the important role of Rho kinase has been demonstrated in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, and heart failure. Cyclophilin A is secreted by vascular smooth muscle cells and inflammatory cells and activated platelets in a Rho-kinase-dependent manner, playing important roles in a wide range of cardiovascular diseases. Thus, the RhoA/Rho-kinase pathway plays crucial roles under both physiological and pathological conditions and is an important therapeutic target in cardiovascular medicine. Recently, functional differences between ROCK1 and ROCK2 have been reported in vitro. ROCK1 is specifically cleaved by caspase-3, whereas granzyme B cleaves ROCK2. However, limited information is available on the functional differences and interactions between ROCK1 and ROCK2 in the cardiovascular system in vivo. Herein, we will review the recent advances about the importance of RhoA/Rho-kinase in the cardiovascular system. PMID- 26838320 TI - Differential Diagnosis of Proliferative Breast Lesions. AB - The correct diagnosis of proliferations within the mammary terminal duct-lobular unit has paramount prognostic and therapeutic implications. Occasionally, the differential diagnosis of compact florid hyperplasia, atypical ductal hyperplasia, and low-grade ductal carcinoma in situ can be quite challenging, with seeming morphologic overlap. This article presents s conceptual and practical understanding of these processes and their impact on subsequent cancer risk, with the intention of assisting the practicing pathologist render accurate and clinically relevant diagnoses for this frequently encountered set of mammary epithelial lesions. PMID- 26838321 TI - Triple-Negative Breast Carcinoma. AB - Triple-negative breast carcinomas (TNBCs) comprise approximately 15% to 20% of breast cancers. Accurate assessment of tumor estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) status is an essential part of classifying tumors into this group. As a group, these tumors are associated with poor clinical outcomes and have been shown to exhibit an increased propensity for hematogenous metastasis to the brain and lungs. Many TNBCs, particularly ductal, not otherwise specified (NOS), and metaplastic carcinomas, show an overlapping characteristic gene expression pattern when evaluated by cDNA microarrays. This group has been termed basal-like because of the similarity with normal breast basal/myoepithelial cells including basal cytokeratin expression and lack of hormone receptor and HER2 expression. The array data have been used to develop multiple immunohistochemical surrogates to identify basal-like tumors in formalin-fixed, paraffin-embedded tissues, most employing basal cytokeratins and epidermal growth factor receptor. Currently, there is no international consensus on biomarkers used to identify tumors as basal-like, and the routine use of the term basal-like in surgical pathology reports is premature. Tumor morphologic features associated with triple-negative status include Nottingham grade 3 with high mitotic rate, pushing border of invasion, geographic tumor necrosis, solid/sheet-like growth pattern, lymphocytic infiltrate, and large central acellular zone. Most breast cancers arising in patients who have a germ-line BRCA1 mutation show similar histologic features and a triple-negative phenotype. Not all TNBCs are associated with an unfavorable prognosis, drawing attention to the heterogeneity of this tumor group and the continued need to link tumor morphology and grade with triple-negative status. This article focuses on histopathology, molecular characterization, carcinogenesis, clinical behavior, and treatment of these tumors. PMID- 26838317 TI - More Than Tiny Sacks: Stem Cell Exosomes as Cell-Free Modality for Cardiac Repair. AB - Stem cell therapy provides immense hope for regenerating the pathological heart, yet has been marred by issues surrounding the effectiveness, unclear mechanisms, and survival of the donated cell population in the ischemic myocardial milieu. Poor survival and engraftment coupled to inadequate cardiac commitment of the adoptively transferred stem cells compromises the improvement in cardiac function. Various alternative approaches to enhance the efficacy of stem cell therapies and to overcome issues with cell therapy have been used with varied success. Cell-free components, such as exosomes enriched in proteins, messenger RNAs, and miRs characteristic of parental stem cells, represent a potential approach for treating cardiovascular diseases. Recently, exosomes from different kinds of stem cells have been effectively used to promote cardiac function in the pathological heart. The aim of this review is to summarize current research efforts on stem cell exosomes, including their potential benefits and limitations to develop a potentially viable therapy for cardiovascular problems. PMID- 26838322 TI - Flat Epithelial Atypia of the Breast. AB - Lesions of the breast characterized by enlarged terminal duct lobular units lined by columnar epithelial cells are being encountered increasingly in breast biopsy specimens. Some of these lesions feature cuboidal to columnar epithelial cells in which the lining cells exhibit cytologic atypia. The role of these lesions (recently designated "flat epithelial atypia" [FEA]) in breast tumor progression is still emerging. FEA commonly coexists with well-developed examples of atypical ductal hyperplasia, low-grade ductal carcinoma in situ, lobular neoplasia, and tubular carcinoma. These findings and those of recent genetic studies suggest that FEA is a neoplastic lesion that may represent a precursor to or the earliest morphologic manifestation of ductal carcinoma in situ. Additional studies are needed to better understand the biologic nature and clinical significance of these lesions. PMID- 26838323 TI - Lobular Carcinoma in Situ, Classical Type and Unusual Variants. AB - The morphologic spectrum of lobular carcinoma in situ (LCIS) includes the classical type and unusual variants recently described. In this article we review the morphology of LCIS and highlight ways to distinguish it from its morphologic mimickers. PMID- 26838325 TI - Encapsulated Papillary Carcinoma of the Breast. AB - Papillary lesions of the breast include a broad spectrum of entities, many of which can be diagnostically challenging for the pathologist. This article focuses on encapsulated papillary carcinoma, a recently proposed term used to describe papillary carcinoma occurring within a cystically dilated duct. Previously considered a variant of papillary ductal carcinoma in situ, the finding that these lesions typically lack myoepithelial cells at their periphery has raised questions about their true nature. This article presents a practical approach to the diagnosis of encapsulated papillary carcinoma with a review of its histologic mimics and clinical significance. PMID- 26838316 TI - Cardiac Mechano-Gated Ion Channels and Arrhythmias. AB - Mechanical forces will have been omnipresent since the origin of life, and living organisms have evolved mechanisms to sense, interpret, and respond to mechanical stimuli. The cardiovascular system in general, and the heart in particular, is exposed to constantly changing mechanical signals, including stretch, compression, bending, and shear. The heart adjusts its performance to the mechanical environment, modifying electrical, mechanical, metabolic, and structural properties over a range of time scales. Many of the underlying regulatory processes are encoded intracardially and are, thus, maintained even in heart transplant recipients. Although mechanosensitivity of heart rhythm has been described in the medical literature for over a century, its molecular mechanisms are incompletely understood. Thanks to modern biophysical and molecular technologies, the roles of mechanical forces in cardiac biology are being explored in more detail, and detailed mechanisms of mechanotransduction have started to emerge. Mechano-gated ion channels are cardiac mechanoreceptors. They give rise to mechano-electric feedback, thought to contribute to normal function, disease development, and, potentially, therapeutic interventions. In this review, we focus on acute mechanical effects on cardiac electrophysiology, explore molecular candidates underlying observed responses, and discuss their pharmaceutical regulation. From this, we identify open research questions and highlight emerging technologies that may help in addressing them. PMID- 26838324 TI - Update on Fibroepithelial Lesions of the Breast. AB - This article focuses on current issues relating to fibroepithelial lesions, predominantly those with cellular stroma, and covers key pathologic features, differential diagnosis, and pitfalls. Phyllodes tumors are emphasized, including the histologic categorization and prognostic features of these lesions. The management of fibroepithelial lesions on needle core biopsy is reviewed. PMID- 26838326 TI - Use of Myoepithelial Cell Markers in the Differential Diagnosis of Benign, In situ, and Invasive Lesions of the Breast. AB - Immunohistochemical markers for myoepithelial cells are commonly used to distinguish invasive from noninvasive lesions in the breast. The approach takes advantage of the fact that conventional invasive carcinomas lack surrounding myoepithelial cells, whereas nearly all benign lesions and in situ carcinomas retain their myoepithelial cell layer. Although conceptually straightforward, the interpretation of myoepithelial cell markers can be complicated by misleading patterns of reactivity (such as stromal or tumor cell staining) or lack of reactivity (due to reduced numbers of myoepithelial cells or variable antigenicity). In this article, we discuss the advantages and disadvantages of commonly used myoepithelial cell markers, their general utility in distinguishing invasive from noninvasive processes, and pitfalls in their interpretation. We also examine whether the detection of myoepithelial cells is helpful in the evaluation of papillary lesions, another common application. Myoepithelial cell markers can be diagnostically useful in the distinction of many benign, in situ, and invasive lesions, but they must be interpreted in conjunction with careful morphologic analysis. PMID- 26838327 TI - Spindle Cell Lesions of the Breast. AB - Spindle cell lesions of the breast represent a heterogeneous group of reactive and neoplastic disorders that commonly present diagnostic challenges. Arguably, the most important of these lesions to recognize is spindle cell carcinoma, a type of metaplastic carcinoma. This review focuses on those spindle cell lesions of the breast that are most likely to be encountered in clinical practice or that produce particular diagnostic difficulties. PMID- 26838328 TI - Lesions of the Nipple. AB - Because of the singular anatomic structure of the nipple, some breast lesions only occur at this site. The overlying skin includes normal Toker cells near the duct orifices. These cells are occasionally so numerous as to be called Toker cell hyperplasia. Ductal carcinoma in situ (DCIS) may involve nipple skin by direct extension from the underlying ducts (Paget disease of the nipple). The numerous skin appendages (eg, sebaceous, apocrine, and eccrine glands(1)) in the nipple and areola are the likely origin of syringomatous adenomas. At the duct orifices, the normal squamous epithelium dips into the breast for a short distance and abruptly transitions to glandular luminal and myoepithelial cells. When keratin-producing cells extend deeper into the ducts, the condition of squamous metaplasia of lactiferous ducts (SMOLD) results. With age, the lactiferous sinuses are subject to weakened duct walls, inspissated secretions, and rupture, which result in the inflammatory masses or nipple discharge associated with duct ectasia. Superficial epithelial proliferations within the large lactiferous sinuses form nipple adenomas, and deeper proliferations often result in large-duct papillomas. Below the areola is a supporting smooth muscle layer that can give rise to leiomyomas, although these tumors are extraordinarily rare. The proximity of these lesions to the skin results in the majority of them presenting as palpable masses, skin changes, or nipple discharge. Biopsy specimens from these lesions may be small, superficial, or fragmented because of concern about maintaining the cosmetic appearance of the nipple and areola. Knowledge of the location of the biopsy, and the clinical presentation, is often essential in making the correct diagnosis. PMID- 26838329 TI - Mucinous Lesions of the Breast. AB - Breast lesions associated with extracellular mucin production are uncommon and constitute a wide spectrum of lesions ranging from benign cyst to mucinous carcinoma. Intracytoplasmic mucin can be seen rarely in benign metaplasias but is a common finding in invasive and in situ carcinomas. In this article, we discuss the differential diagnosis of breast lesions associated with mucin production and other entities that show histologic changes that mimic mucin production. PMID- 26838330 TI - Preface. PMID- 26838332 TI - Structural transition upon hydrogenation of B20 at different charge states: from tubular to disk-like, and to cage-like. AB - Extensive first-principles theoretical investigations indicate that neutral B20 undergoes a dramatic structural transition upon partial hydrogenation, from the tubular D2d B20 (), to the disk-like C2v B20H2 (), and then to the cage-like C2 B20H4 (). Both the singly charged C2v B20(-) () and C2 B20H2(-) () favor 2D disk like planar structures with a filled hexagon (B7) at the center, while C2 B20H4( ) () follows its neutral counterpart with a 3D cage-like geometry. All the doubly charged C2v B20(2-) (), C2 B20H2(2-) (), and C1 B20H4(2-) () turn out to prefer planar or quasi-planar 2D structures over 3D geometries, with the most stable B20H4(2-) () possessing a unique hexagon hole (B6) at the center. Detailed CMO and AdNDP analyses reveal that both the perfect planar B20(2-) () and B20H2 () possess concentric dual pi aromaticity, with two pi-electrons delocalized over the filled hexagon B7 at the center and ten pi-electrons delocalized between the filled B7 and the B13 outer ring, each separately conforming to 4n + 2 Huckel's rule. They are therefore the boron analogues of coronene (D6h C24H12). The quasi planar C2 B20H2(2-) () and C1 B20H4(2-) () also appear to be pi aromatic with one pi system following the 4n + 2 rule. The B20H4(2-) () structure with a hexagon hole may serve as the embryo for monolayer boron alpha sheet. Both the cage-like C2 B20H4 () and C2 B20H4(-) () appear to be 3D aromatic with the large negative NICS values of -51.5 and -55.5 ppm, respectively. The structural changes from to reflect a competition between 2D and 3D aromaticities in these clusters, depending on the extent of hydrogenation and electronic charge states. The PES spectra of B20H2(-) () and B20H4(-) () are predicted to facilitate their future experimental characterizations and production. PMID- 26838331 TI - A word-count approach to analyze linguistic patterns in the reflective writings of medical students. AB - BACKGROUND: Teaching reflection and administering reflective writing assignments to students are widely practiced and discussed in medical education and health professional education. However, little is known about how medical students use language to construct their narratives. Exploring students' linguistic patterns in their reflective writings can facilitate understanding the scope and facets of their reflections and their representational or communication approaches to share their experiences. Moreover, research findings regarding gender differences in language use are inconsistent. Therefore, we attempted to examine how females and males differ in their use of words in reflective writing within our research circumstance to detect the unique and gender-specific approaches to learning and their applications. METHODS: We analyzed the linguistic profiles of psychological process categories in the reflective writings of medical students and examined the difference in word usage between male and female medical students. During the first year of a clinical rotation, 60 fifth-year medical students wrote reflective narratives regarding pediatric patients and the psychosocial challenges faced by the patients and their family members. The narratives were analyzed using the Chinese version of Linguistic Inquiry and Word Count (CLIWC), a text analysis software program. Multivariate procedures were applied for statistical analysis. RESULTS: Cognitive words were most pervasive, averaging 22.16%, whereas perceptual words (2.86%) were least pervasive. Female students used more words related to positive emotions and sadness than did male students. The male students exceeded the female students only in the space category. The major limitation of this study is that CLIWC cannot directly acquire contextual text meanings; therefore, depending on the research topic, further qualitative study of the given texts might be necessary. CONCLUSIONS: To enhance students' empathy toward the psychosocial issues faced by patients and their family members, students should be encouraged to explore the domain of psychological processes by identifying and expressing their affective and perceptual experiences. Researchers in future studies should use outcome measures such as self-awareness or empathy to determine the overall effectiveness of reflective writing and how changes in linguistic patterns affect such outcomes. PMID- 26838333 TI - Physiological lipid composition is vital for homotypic ER membrane fusion mediated by the dynamin-related GTPase Sey1p. AB - Homotypic fusion of the endoplasmic reticulum (ER) is required for generating and maintaining the characteristic reticular ER membrane structures. This organelle membrane fusion process depends on the ER-bound dynamin-related GTPases, such as atlastins in animals and Sey1p in yeast. Here, to investigate whether specific lipid molecules facilitate GTPase-dependent ER membrane fusion directly, we comprehensively evaluated membrane docking and lipid mixing of reconstituted proteoliposomes bearing purified Sey1p and a set of ER-mimicking lipids, including phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylserine, phosphatidic acid, and ergosterol. Remarkably, we revealed that each specific lipid species contributed little to membrane docking mediated by Sey1p. Nevertheless, Sey1p-dependent lipid mixing was strongly reduced by omitting three major acidic lipids from the ER-mimicking set and, moreover, was entirely abolished by omitting either phosphatidylethanolamine or ergosterol. Our reconstitution studies thus established that physiological lipid composition is vital for lipid bilayer rearrangements in GTPase-mediated homotypic ER membrane fusion. PMID- 26838334 TI - Left ventricular diastolic dysfunction in type 2 diabetes patients: a novel 2D strain analysis based on cardiac magnetic resonance imaging. AB - OBJECTIVE: This study was to develop a strain analysis method to evaluate the left ventricular (LV) functions in type 2 diabetic patients with an asymptomatic LV diastolic dysfunction. METHODS: Two groups (10 asymptomatic type 2 diabetic subjects and 10 control ones) were considered. All of the subjects had normal ejection fraction values but impaired diastolic functions assessed by the transmitral blood flow velocity. For each subject, based on cardiac MRI, global indexes including LV volume, LV myocardial mass, cardiac index (CI), and transmitral peak velocity, were measured, and regional indexes (i.e., LV deformation, strain and strain rate) were calculated through an image registration technology. RESULTS: Most of the global indexes did not differentiate between the two groups, except for the CI, LV myocardial mass and transmitral peak velocity. While for the regional indexes, the global LV diastolic dysfunction of the diabetic indicated an increased strain (0.08 +/- 0.044 vs. -0.031 +/- 0.077, p = 0.001) and a reduced strain rate (1.834 +/- 0.909 vs. 3.791 +/- 2.394, p = 0.033) compared to the controls, moreover, the local LV diastolic dysfunction reflected by the strain and strain rate varied, and the degree of dysfunction gradually decreased from the basal level to the apical level. CONCLUSIONS: The results showed that the strain and strain rates are effective to capture the subtle alterations of the LV functions, and the proposed method can be used to estimate the LV myocardial function based on cardiac MRI. PMID- 26838336 TI - Valorization of Flue Gas by Combining Photocatalytic Gas Pretreatment with Microalgae Production. AB - Utilization of flue gas for algae cultivation seems to be a promising route because flue gas from fossil-fuel combustion processes contains the high amounts of carbon (CO2) and nitrogen (NO) that are required for algae growth. NO is a poor nitrogen source for algae cultivation because of its low reactivity and solublilty in water and its toxicity for algae at high concentrations. Here, we present a novel strategy to valorize NO from flue gas as feedstock for algae production by combining a photocatalytic gas pretreatment unit with a microalgal photobioreactor. The photocatalytic air pretreatment transforms NO gas into NO2 gas and thereby enhances the absorption of NOx in the cultivation broth. The absorbed NOx will form NO2(-) and NO3(-) that can be used as a nitrogen source by algae. The effect of photocatalytic air pretreatment on the growth and biomass productivity of the algae Thalassiosira weissflogii in a semicontinuous system aerated with a model flue gas (1% CO2 and 50 ppm of NO) is investigated during a long-term experiment. The integrated system makes it possible to produce algae with NO from flue gas as the sole nitrogen source and reduces the NOx content in the exhaust gas by 84%. PMID- 26838335 TI - A new dynamic six degrees of freedom disc-loading simulator allows to provoke disc damage and herniation. AB - PURPOSE: The cause of disc herniation is not well understood yet. It is assumed that heavy lifting and extreme postures can cause small injuries starting either in the inner anulus or from the outside close to the endplate. Such injuries are accumulated over years until its structure is weakened and finally a single loading event leads to a sudden failure of the last few intact lamellae. This paper describes a novel, custom-developed dynamic 6-DOF disc-loading simulator that allows complex loading to provoke such disc damage and herniations. METHODS: The machine's axes are driven by six independent servomotors providing high loads (10 kN axial compression, 2 kN shear, 100 Nm torque) up to 5 Hz. A positional accuracy test was conducted to validate the machine. Subsequently, initial experiments with lumbar ovine motion segments under complex loading were performed. After testing, the discs were examined in an ultra-high field MRI (11.7 T). A three-dimensional reconstruction was performed to visualise the internal disc lesions. RESULTS: Validation tests demonstrated positioning with an accuracy of <=0.08 degrees /<=0.026 mm at 0.5 Hz and <=0.27 degrees /<=0.048 mm at 3.0 Hz with amplitudes of +/-17 degrees /+/-2 mm. Typical failure patterns and herniations could be provoked with complex asymmetrical loading protocols. Loading with axial compression, flexion, lateral bending and torsion lead in 8 specimens to 4 herniated discs, two protrusions and two delaminations. All disc failures occurred in the posterior region of the disc. CONCLUSION: This new dynamic disc-loading simulator has proven to be able to apply complex motion combinations and allows to create artificial lesions in the disc with complex loading protocols. The aim of further tests is to better understand the mechanisms by which disc failure occurs at the microstructural level under different loading conditions. Visualisation with ultra-high field MRI at different time points is a promising method to investigate the gradual development of such lesions, which may finally lead to disc failure. These kinds of experiments will help to better investigate the mechanical failure of discs to provide new insights into the initiation of intervertebral disc herniation. This device will also serve for many other applications in spine biomechanics research. PMID- 26838339 TI - Cell Surface Display of Four Types of Solanum nigrum Metallothionein on Saccharomyces cerevisiae for Biosorption of Cadmium. AB - We displayed four types of Solanum nigrum metallothionein (SMT) for the first time on the surface of Saccharomyces cerevisiae using an alpha-agglutinin-based display system. The SMT genes were amplified by RT-PCR. The plasmid pYES2 was used to construct the expression vector. Transformed yeast strains were confirmed by PCR amplification and custom sequencing. Surface-expressed metallothioneins were indirectly indicated by the enhanced cadmium sorption capacity. Flame atomic absorption spectrophotometry was used to examine the concentration of Cd(2+) in this study. The transformed yeast strains showed much higher resistance ability to Cd(2+) compared with the control. Strikingly, their Cd(2+) accumulation was almost twice as much as that of the wild-type yeast cells. Furthermore, surface engineered yeast strains could effectively adsorb ultra-trace cadmium and accumulate Cd(2+) under a wide range of pH levels, from 3 to 7, without disturbing the Cu(2+) and Hg(2+). Four types of surfaceengineered Saccharomyces cerevisiae strains were constructed and they could be used to purify Cd(2+) contaminated water and adsorb ultra-trace cadmium effectively. The surface engineered Saccharomyces cerevisiae strains would be useful tools for the bioremediation and biosorption of environmental cadmium contaminants. PMID- 26838340 TI - Biological Methanol Production by a Type II Methanotroph Methylocystis bryophila. AB - Methane (CH4) is the most abundant component in natural gas. To reduce its harmful environmental effect as a greenhouse gas, CH4 can be utilized as a low cost feed for the synthesis of methanol by methanotrophs. In this study, several methanotrophs were examined for their ability to produce methanol from CH4; including Methylocella silvestris, Methylocystis bryophila, Methyloferula stellata, and Methylomonas methanica. Among these methanotrophs, M. bryophila exhibited the highest methanol production. The optimum process parameters aided in significant enhancement of methanol production up to 4.63 mM. Maximum methanol production was observed at pH 6.8, 30 degrees C, 175 rpm, 100 mM phosphate buffer, 50 mM MgCl2 as a methanol dehydrogenase inhibitor, 50% CH4 concentration, 24 h of incubation, and 9 mg of dry cell mass ml(-1) inoculum load, respectively. Optimization of the process parameters, screening of methanol dehydrogenase inhibitors, and supplementation with formate resulted in significant improvements in methanol production using M. bryophila. This report suggests, for the first time, the potential of using M. bryophila for industrial methanol production from CH4. PMID- 26838341 TI - The Actinobacterium Corynebacterium glutamicum, an Industrial Workhorse. AB - Starting as a glutamate producer, Corynebacterium glutamicum has played a variety of roles in the industrial production of amino acids, one of the most important areas of white biotechnology. From shortly after its genome information became available, C. glutamicum has been applied in various production processes for value-added chemicals, fuels, and polymers, as a key organism in industrial biotechnology alongside the surprising progress in systems biology and metabolic engineering. In addition, recent studies have suggested another potential for C. glutamicum as a synthetic biology platform chassis that could move the new era of industrial microbial biotechnology beyond the classical field. Here, we review the recent progress and perspectives in relation to C. glutamicum, which demonstrate it as one of the most promising and valuable workhorses in the field of industrial biotechnology. PMID- 26838342 TI - Co-Localization of GABA Shunt Enzymes for the Efficient Production of Gamma Aminobutyric Acid via GABA Shunt Pathway in Escherichia coli. AB - Gamma-aminobutyric acid (GABA) is a non-protein amino acid, which is an important inhibitor of neurotransmission in the human brain. GABA is also used as the precursor of biopolymer Nylon-4 production. In this study, the carbon flux from the tricarboxylic acid cycle was directed to the GABA shunt pathway for the production of GABA from glucose. The GABA shunt enzymes succinate-semialdehyde dehydrogenase (GabD) and GABA aminotransferase (GabT) were co-localized along with the GABA transporter (GadC) by using a synthetic scaffold complex. The co localized enzyme scaffold complex produced 0.71 g/l of GABA from 10 g/l of glucose. Inactivation of competing metabolic pathways in mutant E. coli strains XBM1 and XBM6 increased GABA production 13% to reach 0.80 g/l GABA by the enzymes co-localized and expressed in the mutant strains. The recombinant E. coli system developed in this study demonstrated the possibility of the pathway of the GABA shunt as a novel GABA production pathway. PMID- 26838343 TI - Involvement of Lysosome Membrane Permeabilization and Reactive Oxygen Species Production in the Necrosis Induced by Chlamydia muridarum Infection in L929 Cells. AB - Chlamydiae, obligate intracellular bacteria, are associated with a variety of human diseases. The chlamydial life cycle undergoes a biphasic development: replicative reticulate bodies (RBs) phase and infectious elementary bodies (EBs) phase. At the end of the chlamydial intracellular life cycle, EBs have to be released to the surrounded cells. Therefore, the interactions between Chlamydiae and cell death pathways could greatly influence the outcomes of Chlamydia infection. However, the underlying molecular mechanisms remain elusive. Here, we investigated host cell death after Chlamydia infection in vitro, in L929 cells, and showed that Chlamydia infection induces cell necrosis, as detected by the propidium iodide (PI)-Annexin V double-staining flow-cytometric assay and Lactate dehydrogenase (LDH) release assay. The production of reactive oxygen species (ROS), an important factor in induction of necrosis, was increased after Chlamydia infection, and inhibition of ROS with specific pharmacological inhibitors, diphenylene iodonium (DPI) or butylated hydroxyanisole (BHA), led to significant suppression of necrosis. Interestingly, live-cell imaging revealed that Chlamydia infection induced lysosome membrane permeabilization (LMP). When an inhibitor upstream of LMP, CA-074-Me, was added to cells, the production of ROS was reduced with concomitant inhibition of necrosis. Taken together, our results indicate that Chlamydia infection elicits the production of ROS, which is dependent on LMP at least partially, followed by induction of host-cell necrosis. To our best knowledge, this is the first live-cell-imaging observation of LMP post Chlamydia infection and report on the link of LMP to ROS to necrosis during Chlamydia infection. PMID- 26838344 TI - Intrinsically motivated oculomotor exploration guided by uncertainty reduction and conditioned reinforcement in non-human primates. AB - Intelligent animals have a high degree of curiosity--the intrinsic desire to know -but the mechanisms of curiosity are poorly understood. A key open question pertains to the internal valuation systems that drive curiosity. What are the cognitive and emotional factors that motivate animals to seek information when this is not reinforced by instrumental rewards? Using a novel oculomotor paradigm, combined with reinforcement learning (RL) simulations, we show that monkeys are intrinsically motivated to search for and look at reward-predictive cues, and that their intrinsic motivation is shaped by a desire to reduce uncertainty, a desire to obtain conditioned reinforcement from positive cues, and individual variations in decision strategy and the cognitive costs of acquiring information. The results suggest that free-viewing oculomotor behavior reveals cognitive and emotional factors underlying the curiosity driven sampling of information. PMID- 26838345 TI - Functionality of Selected Aromatic Lamiaceae in Attracting Pollinators in Central Spain. AB - Planting floral margins in agricultural landscapes has been shown to increase the abundance of pollinators in agro-ecosystems. However, to create efficient margins, it is necessary to use attractive, not weedy native plants with different blooming periods to prolong the availability of floral resources. Six native perennial plants of the Lamiaceae with different blooming periods were studied in a randomized block design, with the final aim to select the most efficient plants in floral mixtures by studying relationships between their floral phenology, floral density, and attractiveness to pollinators in Central Spain. In addition, their spatial expansion, i.e., potential weediness, was estimated under the field conditions, as the final purpose of the plants is to be implemented within the agro-ecosystems. The results showed that plant species with higher floral density (Nepeta tuberosa L. and Hyssopus officinalis L.) showed significantly higher attractiveness to pollinators and enhanced the attractiveness of floral mixtures. Species that bloomed in early spring (Salvia verbenaca L.) and in summer (Melissa officinalis L. and Thymbra capitata L.) did not efficiently contribute to the attractiveness of the mixtures to pollinators. In addition, besides high floral density of Salvia officinalis L. and N. tuberosa in the spring, warm and dry weather in spring 2012 enhanced the activity of bees, while cold and rainy weather in spring 2013 enhanced the activity of hoverflies. None of the plants showed weedy growth and so posed no danger of invading adjacent crops. PMID- 26838346 TI - A Modular System of 3D Printed Emergence Traps for Studying the Biology of Shot Hole Borers and Other Scolytinae. AB - A modular system for studying the biology of Scolytinae using 3D printed emergence traps is presented. This system consists of traps that can be used for the introduction of beetles into trees as well as for the determination of the number of offspring emerging from trees and branches, and their production of frass and sawdust. Open-source files used for printing these traps have been deposited as supplementary material and can be downloaded for trap production by students of Scolytinae with access to a 3D printer. The cost in material for the production of a single emergence trap on the printer used here is approximately $1.30, with a print time of less than 90 min. PMID- 26838347 TI - Landscape Patterns of Colonization by Subterranean Termites (Isoptera: Rhinotermitidae) in Missouri Neighborhoods. AB - In Missouri, the relative abundances of subterranean termite species differ between undeveloped forest and urban landscapes. Reticulitermes hageni Banks occurs in greater relative proportions in forested landscapes, while Reticulitermes flavipes (Kollar) occurs in greater relative proportions in urban landscapes. Thus, subterranean termite communities appear to change at some point as landscapes are converted from undeveloped to urban. It is not known if communities change quickly in direct response to urban development, or if changes occur over time in altered urban landscapes. The purpose of this study is to examine how landscape factors are associated with subterranean termite communities and patterns of colonization as subdivisions are constructed and age. Subterranean termites were collected from 25 areas in Columbia, MO, that were classified along a gradient of urbanization to include 1) undeveloped landscapes; 2) recently disturbed transitional landscapes; 3) 10-yr-old subdivisions; and 4) 20-yr-old subdivisions. Subterranean termite communities were assessed by identifying species using polymerase chain reaction-based restriction fragment length polymorphisms. The interactions between landscape features and subterranean termites were examined using GIS software. Relative proportions of Reticulitermes spp. in communities of forest landscapes and urban areas are similar to previous reports for the state of Missouri. Termite communities appear to be locally eliminated after soils are disturbed or removed during subdivision development, although remnant colonies can persist in areas that are not disturbed. Reticulitermes flavipes appears to colonize subdivisions quickly regardless of historical or contemporary landscape; however, R. hageni colonization generally becomes more common as subdivisions age and gradually become more forested. PMID- 26838348 TI - Erratum to: Evaluating quantitative and conceptual models of speech production: how does SLAM fare? PMID- 26838350 TI - Critical Care of Brain Reperfusion. AB - Over the last few decades, the management of acute ischemic stroke has undergone significant advancements with the introduction of intravenous thrombolysis and more recently punctuated by the success of endovascular mechanical thrombectomy trials for large vessel occlusion. These advancements have transformed the practice of neurocritical care. In this review, we present a case-based discussion of common brain reperfusion techniques with an emphasis on complication recognition and management. The article encompasses recent evidence based recommendations as well as some of our own institutional protocols. PMID- 26838349 TI - Surgery for Dystonia and Tremor. AB - Surgical procedures for dystonia and tremor have evolved over the past few decades, and our understanding of risk, benefit, and predictive factors has increased substantially in that time. Deep brain stimulation (DBS) is the most utilized surgical treatment for dystonia and tremor, though lesioning remains an effective option in appropriate patients. Dystonic syndromes that have shown a substantial reduction in severity secondary to DBS are isolated dystonia, including generalized, cervical, and segmental, as well as acquired dystonia such as tardive dystonia. Essential tremor is quite amenable to DBS, though the response of other forms of postural and kinetic tremor is not nearly as robust or consistent based on available evidence. Regarding targeting, DBS lead placement in the globus pallidus internus has shown marked efficacy in dystonia reduction. The subthalamic nucleus is an emerging target, and increasing evidence suggests that this may be a viable target in dystonia as well. The ventralis intermedius nucleus of the thalamus is the preferred target for essential tremor, though targeting the subthalamic zone/caudal zona incerta has shown promise and may emerge as another option in essential tremor and possibly other tremor disorders. In the carefully selected patient, DBS and lesioning procedures are relatively safe and effective for the management of dystonia and tremor. PMID- 26838351 TI - Guidelines for Management of Hyperlipidemia: Implications for Treatment of Patients with Stroke Secondary to Atherosclerotic Disease. AB - After careful review of randomized cardiovascular outcomes trial data, the 2013 ACC/AHA cholesterol guideline focused on using the appropriate intensity of statin therapy to reduce atherosclerotic cardiovascular disease (ASCVD) risk and moved away from recommending specific low-density lipoprotein cholesterol (LDL-C) treatment targets. In patients who have had a stroke or other clinical ASCVD event, a high-intensity statin should be initiated up to age 75 years unless there are safety concerns, including a history of hemorrhagic stroke. A moderate intensity statin is recommended if there are safety concerns or age is greater than 75 years. Atorvastatin 40-80 mg and rosuvastatin 20-40 mg are considered high-intensity statins. These new guidelines avoid unnecessary usage of non statins to achieve specific LDL-C values, thus avoiding potential adverse effects or use of an inadequate statin intensity in patients who are "at goal." When non statins are considered for additional LDL-C lowering, ezetimibe is the only non statin clearly shown to further reduce ASCVD risk when added to background statin therapy. PMID- 26838352 TI - The "Liquid Biopsy": the Role of Circulating DNA and RNA in Central Nervous System Tumors. AB - The detection of tumor-derived circulating nucleic acids in patients with cancer, known as the "liquid biopsy," has expanded from use in plasma to other bodily fluids in an increasing number of malignancies. Circulating nucleic acids could be of particular use in central nervous system tumors as biopsy carries a 5-7 % risk of major morbidity. This application presents unique challenges that have limited the use of cell-free DNA and RNA in the diagnosis and monitoring of CNS tumors. Recent work suggests that cerebrospinal fluid may be a useful source of CNS tumor-derived circulating nucleic acids. In this review, we discuss the available data and future outlook on the use of the liquid biopsy for CNS tumors. PMID- 26838353 TI - Immediate therapist self-disclosure bolsters the effect of brief integrative psychotherapy on psychiatric symptoms and the perceptions of therapists: A randomized clinical trial. AB - OBJECTIVE: We report a first randomized clinical trial examining the effect of immediate and non-immediate therapist self-disclosure in the context of a brief integrative psychotherapy for mild to moderate distress. METHOD: A total of 86 patients with mild to moderate forms of distress were randomly divided into three 12-session integrative psychotherapy conditions based primarily on [Hill, C. E. (2009). Helping skills: Facilitating, exploration, insight, and action (3rd ed.). Washington, DC: American Psychological Association.] three-stage model. Therapists trained in this treatment modality were instructed to use either immediate self-disclosure (expressing feelings towards the patient/treatment/therapeutic relationship) or non-immediate self-disclosure (expressing personal or factual information regarding the therapist's life outside the treatment). In the comparison condition, the therapists were instructed to refrain from self-disclosure altogether. RESULTS: Immediate therapist self-disclosure reduced psychiatric symptoms among patients with elevated pretreatment symptoms (as assessed by the Brief Symptoms Inventory) and bolstered a favorable perception of the therapist. Therapists in both the immediate and non-immediate self-disclosure group evaluated themselves more favorably than their counterparts in the non-disclosure group. CONCLUSIONS: Therapist self-disclosure, particularly of the immediate type, might enhance the effect of brief integrative treatment on psychiatric symptoms of high symptomatic patients and contribute to favorable perception of therapists. PMID- 26838354 TI - Evaluation of cardiac masses by CMR-strengths and pitfalls: a tertiary center experience. AB - Cardiovascular magnetic resonance (CMR) imaging is often considered the reference method to assess cardiac tumors. However, little data exists concerning the effectiveness of CMR for the accurate diagnosis of cardiac masses. We sought to understand the diagnostic value of CMR for evaluation of suspected cardiac mass. A total of 249 consecutive CMR cases performed at a single center from January 2005 to June 2013 for evaluation of masses found on echocardiography or computed tomography (CT) were included. All the clinical data and imaging features of these patients were retrospectively reviewed and medical records were verified for follow up care. More than half of the patients referred for evaluation of masses found at echocardiography or CT were found to have no evidence of mass by CMR. CMR correctly differentiated between thrombus and myxoma in 88.4 % cases. Malignant masses were accurately diagnosed on CMR. However, CMR missed or misdiagnosed a few cases of benign masses. Diagnosing cardiac masses remains an important use for imaging, despite technical difficulties with current imaging modalities. CMR can play a key role in confirming presence or absence of a mass. Additionally, in the presence of a mass, CMR can provide accurate differentiation of pseudomasses, benign and malignant masses. However, the limitations of CMR must be recognized. PMID- 26838355 TI - Endoscopic-assisted retrieval of retained lacrimal stent material in congenital nasolacrimal duct obstruction without dacryocystorhinostomy. AB - We report a 3-year-old child with history of congenital nasolacrimal duct obstruction who failed lacrimal probing and underwent bicanalicular intubation. Removal of stent from the superior punctum was unsuccessful and it was trapped in the lacrimal sac. We performed endonasal endoscopic-assisted retrieval of retained stent material without necessitating dacryocystorhinostomy (DCR). There was no recurrence of infection and nasolacrimal duct obstruction symptoms during 6 months of follow-up. PMID- 26838357 TI - Variations in task constraints shape emergent performance outcomes and complexity levels in balancing. AB - This study investigated the extent to which specific interacting constraints of performance might increase or decrease the emergent complexity in a movement system, and whether this could affect the relationship between observed movement variability and the central nervous system's capacity to adapt to perturbations during balancing. Fifty-two healthy volunteers performed eight trials where different performance constraints were manipulated: task difficulty (three levels) and visual biofeedback conditions (with and without the center of pressure (COP) displacement and a target displayed). Balance performance was assessed using COP-based measures: mean velocity magnitude (MVM) and bivariate variable error (BVE). To assess the complexity of COP, fuzzy entropy (FE) and detrended fluctuation analysis (DFA) were computed. ANOVAs showed that MVM and BVE increased when task difficulty increased. During biofeedback conditions, individuals showed higher MVM but lower BVE at the easiest level of task difficulty. Overall, higher FE and lower DFA values were observed when biofeedback was available. On the other hand, FE reduced and DFA increased as difficulty level increased, in the presence of biofeedback. However, when biofeedback was not available, the opposite trend in FE and DFA values was observed. Regardless of changes to task constraints and the variable investigated, balance performance was positively related to complexity in every condition. Data revealed how specificity of task constraints can result in an increase or decrease in complexity emerging in a neurobiological system during balance performance. PMID- 26838358 TI - Retinotopy and attention to the face and house images in the human visual cortex. AB - Attentional modulation of the neural activities in human visual areas has been well demonstrated. However, the retinotopic activities that are driven by face and house images and attention to face and house images remain unknown. In the present study, we used images of faces and houses to estimate the retinotopic activities that were driven by both the images and attention to the images, driven by attention to the images, and driven by the images. Generally, our results show that both face and house images produced similar retinotopic activities in visual areas, which were only observed in the attention + stimulus and the attention conditions, but not in the stimulus condition. The fusiform face area (FFA) responded to faces that were presented on the horizontal meridian, whereas parahippocampal place area (PPA) rarely responded to house at any visual field. We further analyzed the amplitudes of the neural responses to the target wedge. In V1, V2, V3, V3A, lateral occipital area 1 (LO-1), and hV4, the neural responses to the attended target wedge were significantly greater than those to the unattended target wedge. However, in LO-2, ventral occipital areas 1 and 2 (VO-1 and VO-2) and FFA and PPA, the differences were not significant. We proposed that these areas likely have large fields of attentional modulation for face and house images and exhibit responses to both the target wedge and the background stimuli. In addition, we proposed that the absence of retinotopic activity in the stimulus condition might imply no perceived difference between the target wedge and the background stimuli. PMID- 26838356 TI - Age-related effects of increasing postural challenge on eye movement onset latencies to visual targets. AB - When a single light cue is given in the visual field, our eyes orient towards it with an average latency of 200 ms. If a second cue is presented at or around the time of the response to the first, a secondary eye movement occurs that represents a reorientation to the new target. While studies have shown that eye movement latencies to 'single-step' targets may or may not be lengthened with age, secondary eye movements (during 'double-step' displacements) are significantly delayed with increasing age. The aim of this study was to investigate whether the postural challenge posed simply by standing (as opposed to sitting) results in significantly longer eye movement latencies in older adults compared to the young. Ten young (<35 years) and 10 older healthy adults (>65 years) participated in the study. They were required to fixate upon a central target and move their eyes in response to 2 types of stimuli: (1) a single-step perturbation of target position either 15 degrees to the right or left and (2) a double-step target displacement incorporating an initial target jump to the right or left by 15 degrees , followed after 200 ms, by a shift of target position to the opposite side (e.g. +15 degrees then -15 degrees ). All target displacement conditions were executed in sit and stand positions with the participant at the same distance from the targets. Eye movements were recorded using electro-oculography. Older adults did not show significantly longer eye movement latencies than the younger adults for single-step target displacements, and postural configuration (stand compared to sit) had no effect upon latencies for either group. We categorised double-step trials into those during which the second light changed after or before the onset of the eye shift to the first light. For the former category, young participants showed faster secondary eye shifts to the second light in the standing position, while the older adults did not. For the latter category of double-step trial, young participants showed no significant difference between sit and stand secondary eye movement latencies, but older adults were significantly longer standing compared to sitting. The older adults were significantly longer than the younger adults across both postural conditions, regardless of when the second light change occurred during the eye shift to the first light. We suggest that older adults require greater time and perhaps attentional processes to execute eye movements to unexpected changes in target position when faced with the need to maintain standing balance. PMID- 26838359 TI - Looking away: distractor influences on saccadic trajectory and endpoint in prosaccade and antisaccade tasks. AB - Successful target selection often occurs concurrently with distractor inhibition. A better understanding of the former thus requires a thorough study of the competition that arises between target and distractor representations. In the present study, we explore whether the presence of a distractor influences saccade processing via interfering with visual target and/or saccade goal representations. To do this, we asked participants to make either pro- or antisaccade eye movements to a target and measured the change in their saccade trajectory and landing position (collectively referred to as deviation) in response to distractors placed near or far from the saccade goal. The use of an antisaccade paradigm may help to distinguish between stimulus- and goal-related distractor interference, as unlike with prosaccades, these two features are dissociated in space when making a goal-directed antisaccade response away from a visual target stimulus. The present results demonstrate that for both pro- and antisaccades, distractors near the saccade goal elicited the strongest competition, as indicated by greater saccade trajectory deviation and landing position error. Though distractors far from the saccade goal elicited, on average, greater deviation away in antisaccades than in prosaccades, a time course analysis revealed a significant effect of far-from-goal distractors in prosaccades as well. Considered together, the present findings support the view that goal-related representations most strongly influence the saccade metrics tested, though stimulus-related representations may play a smaller role in determining distractor-based interference effects on saccade execution under certain circumstances. Further, the results highlight the advantage of considering temporal changes in distractor-based interference. PMID- 26838360 TI - Drawing ellipses in water: evidence for dynamic constraints in the relation between velocity and path curvature. AB - Several types of continuous human movements comply with the so-called Two-Thirds Power Law (2/3-PL) stating that velocity (V) is a power function of the radius of curvature (R) of the endpoint trajectory. The origin of the 2/3-PL has been the object of much debate. An experiment investigated further this issue by comparing two-dimensional drawing movements performed in air and water. In both conditions, participants traced continuously quasi-elliptic trajectories (period T = 1.5 s). Other experimental factors were the movement plane (horizontal/vertical), and whether the movement was performed free-hand, or by following the edge of a template. In all cases a power function provided a good approximation to the V-R relation. The main result was that the exponent of the power function in water was significantly smaller than in air. This appears incompatible with the idea that the power relationship depends only on kinematic constraints and suggests a significant contribution of dynamic factors. We argue that a satisfactory explanation of the observed behavior must take into account the interplay between the properties of the central motor commands and the visco-elastic nature of the mechanical plant that implements the commands. PMID- 26838363 TI - Habitat specificity enhances genetic differentiation in two species of aquatic Podostemaceae in Japan. AB - PREMISE OF THE STUDY: Species with habitat specificity show restricted distribution, and the limited dispersal provides opportunity for long-term isolation. Aquatic Podostemaceae grow on rocks in river rapids, which are extreme habitats for angiosperms. To infer the diversification process of the podostemad species in such specific habitats, we investigated environmental factors shaping their distribution and the relationship between their distribution and genetic structure. METHODS: We used Hydrobryum japonicum and Cladopus doianus, which have contrasting distributions (i.e., narrower and wider, respectively) in southern Kyushu, Japan. Environmental factors contributing to their distribution were estimated by ecological niche modeling. Using polymorphisms in chloroplast DNA, we performed population genetic analyses of 13 H. japonicum populations occurring in nearby river basins and eight C. doianus populations in distant rivers. KEY RESULTS: Estimation of distribution probability showed great contributions of geology and temperature to the distribution of these populations, suggesting that the species grow on volcanic rocks in relatively warm areas. Genetic analyses revealed higher interpopulational genetic diversity than intrapopulational diversity and strong differentiation between rivers in both species. No correlation between genetic and geographic distances was detected among the C. doianus populations, in contrast to the significant correlation observed in the H. japonicum populations. CONCLUSIONS: The high-level genetic differentiations among populations of the two species may result from their limited dispersal. Their restricted habitats, which are primarily characterized by volcanic rocks in rapids and lower temperatures in winter, may enhance isolation among populations in distant rivers. PMID- 26838362 TI - Brain Invasion by CD4(+) T Cells Infected with a Transmitted/Founder HIV-1BJZS7 During Acute Stage in Humanized Mice. AB - Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) is one of the common causes of cognitive dysfunction and morbidity among infected patients. However, to date, it remains unknown if a transmitted/founder (T/F) HIV 1 leads to neurological disorders during acute phase of infection. Since it is impossible to answer this question in humans, we studied NOD.Cg-Prkdc scid Il2rgtm1Wjl/SzJ mice (NSG) reconstituted with human PBMC (NSG-HuPBL), followed by the peritoneal challenge with the chronic HIV-1JR-FL and the T/F HIV-1BJZS7, respectively. By measuring viral load, P24 antigenemia and P24(+) cells in peripheral blood and various tissue compartments, we found that systemic infections were rapidly established in NSG-HuPBL mice by both HIV-1 strains. Although comparable peripheral viral loads were detected during acute infection, the T/F virus appeared to cause less CD4(+) T cell loss and less numbers of infected cells in different organs and tissue compartments. Both viruses, however, invaded brains with P24(+)/CD3(+) T cells detected primarily in meninges, cerebral cortex and perivascular areas. Critically, brain infections with HIV-1JR-FL but not with HIV-1BJZS7 resulted in damaged neurons together with activated microgliosis and astrocytosis as determined by significantly increased numbers of Iba1(+) microglial cells and GFAP(+) astrocytes, respectively. The increased Iba1(+) microglia was correlated positively with levels of P24 antigenemia and negatively with numbers of NeuN(+) neurons in brains of infected animals. Our findings, therefore, indicate the establishment of two useful NSG HuPBL models, which may facilitate future investigation of mechanisms underlying HIV-1-induced microgliosis and astrocytosis. PMID- 26838361 TI - Mitoapocynin Treatment Protects Against Neuroinflammation and Dopaminergic Neurodegeneration in a Preclinical Animal Model of Parkinson's Disease. AB - Mitochondrial dysfunction, oxidative stress and neuroinflammation have been implicated as key mediators contributing to the progressive degeneration of dopaminergic neurons in Parkinson's disease (PD). Currently, we lack a pharmacological agent that can intervene in all key pathological mechanisms, which would offer better neuroprotective efficacy than a compound that targets a single degenerative mechanism. Herein, we investigated whether mito-apocynin (Mito-Apo), a newly-synthesized and orally available derivative of apocynin that targets mitochondria, protects against oxidative damage, glial-mediated inflammation and nigrostriatal neurodegeneration in cellular and animal models of PD. Mito-Apo treatment in primary mesencephalic cultures significantly attenuated the 1-methyl-4-phenylpyridinium (MPP(+))-induced loss of tyrosine hydroxylase (TH)-positive neuronal cells and neurites. Mito-Apo also diminished MPP(+) induced increases in glial cell activation and inducible nitric oxide synthase (iNOS) expression. Additionally, Mito-Apo decreased nitrotyrosine (3-NT) and 4 hydroxynonenol (4-HNE) levels in primary mesencephalic cultures. Importantly, we assessed the neuroprotective property of Mito-Apo in the MPTP mouse model of PD, wherein it restored the behavioral performance of MPTP-treated mice. Immunohistological analysis of nigral dopaminergic neurons and monoamine measurement further confirmed the neuroprotective effect of Mito-Apo against MPTP induced nigrostriatal dopaminergic neuronal loss. Mito-Apo showed excellent brain bioavailability and also markedly attenuated MPTP-induced oxidative markers in the substantia nigra (SN). Furthermore, oral administration of Mito-Apo significantly suppressed MPTP-induced glial cell activation, upregulation of proinflammatory cytokines, iNOS and gp91phox in IBA1-positive cells of SN. Collectively, these results demonstrate that the novel mitochondria-targeted compound Mito-Apo exhibits profound neuroprotective effects in cellular and pre clinical animal models of PD by attenuating oxidative damage and neuroinflammatory processes. PMID- 26838364 TI - Postglacial expansion pathways of red mangrove, Rhizophora mangle, in the Caribbean Basin and Florida. AB - PREMISE OF THE STUDY: The Last Glacial Maximum (LGM) was a period of massive range contraction. Post-LGM, water-dispersed coastal species, including the red mangrove (Rhizophora mangle), expanded poleward as propagules were transported by ocean currents. We assessed postglacial marine expansion pathways for R. mangle within the Caribbean Basin and Florida. METHODS: Six microsatellite loci were used to genotype 237 individuals from nine R. mangle populations in the Caribbean, Florida, and Northwest Africa. We evaluated genetic variation, population structure, gene flow along alternative post-LGM expansion pathways to Florida, and potential long-distance dispersal (LDD) from West Africa to Caribbean islands. KEY RESULTS: These R. mangle populations had substantial genetic structure (FST = 0.37, P < 0.0001) with three discrete population clusters (Caribbean mainland, Caribbean islands, and Florida). Genetic connectivity along the mainland pathway (Caribbean mainland to Florida) vs. limited gene dispersal along the Antilles Island pathway (Caribbean islands to Florida) supported Florida recolonization from Caribbean mainland sources. Genetic similarity of Northwest Africa and two Caribbean islands provided evidence for trans-Atlantic LDD. We did not find a pattern of decreasing genetic diversity with latitude. CONCLUSIONS: We outline a complex expansion history for R. mangle, with discrete pathways of recolonization for Florida and Caribbean islands. Contrary to expectation, connectivity to putative Caribbean mainland refugial populations via ocean currents, and not latitude, appears to dictate genetic diversity within Caribbean island and Florida R. mangle. These findings provide a framework for further investigation of additional water-dispersed neotropical species, and insights for management initiatives. PMID- 26838365 TI - How do fungal partners affect the evolution and habitat preferences of mycoheterotrophic plants? A case study in Gastrodia. AB - PREMISE OF THE STUDY: Since mycoheterotrophic plants (MHPs) completely depend on their mycorrhizal fungi for carbon, selection of fungal partners has an important role in the speciation of MHPs. However, the causes and mechanisms of mycobiont changes during speciation are not clear. We tested fungal partner shifts and changes in mycorrhizal specificity during speciation of three closely related MHPs-Gastrodia confusa (Gc), G. pubilabiata (Gp), and G. nipponica (Gn) (Orchidaceae)-and correlations between these changes and the vegetation types where each species grows. METHODS: We investigated the diversity of mycobionts of the three species by sequencing nrDNA ITS, and the sequence data were subjected to test changes in fungal specificity and fungal partner shifts among the three species. Furthermore, we conducted multivariate analysis to test for differences in mycobiont communities of vegetation types where each species grows. KEY RESULTS: Two saprobic Basidiomycota, Marasmiaceae and Mycenaceae, were dominant fungal partners of the three species, and Gn was simultaneously associated with the ectomycorrhizal Russulaceae and Sebacinaceae. Although mycobiont composition differed among the three species, they also sometimes shared identical fungal species. Multivariate analysis revealed that mycobiont communities of the three species in bamboo thickets differed significantly from those in other vegetation types. CONCLUSIONS: Fungal partner shifts are not necessarily associated with the evolution of MHPs, and fungal specificity of Gc and Gp was significantly higher than that of Gn, implying that the specificity fluctuates during speciation. Further, Gc exclusively inhabits bamboo thickets, which suggests that adaptation to particular fungi specific to bamboo thickets triggered speciation of this species. PMID- 26838366 TI - Contemporary patterns of genetic diversity of cedrela fissilis offer insight into the shaping of seasonal forests in eastern South America. AB - PREMISE OF THE STUDY: We investigated how genetic diversity is distributed across the range of Cedrela fissilis, a tree species associated with seasonal neotropical forests, to gain insights into competing biogeographic scenarios that explain how disjunct distributions of these forests were shaped. METHODS: A total of 250 samples were sampled from 18 sites across the species' range in Brazil and eastern Bolivia and genotyped with 10 microsatellite loci. An array of complementary methods-F statistics, analyses of molecular variance (AMOVA), and clustering analyses-assessed genetic diversity, population differentiation, and structure. KEY RESULTS: Most of the genetic diversity (82.5%) was partitioned within populations, but about 12% was due to differences among groups of populations on either side of the Cerrado or located within the Cerrado; mean expected heterozygosity and mean observed heterozygosity were 0.821 and 0.704, respectively. The 250 samples were sorted into two Bayesian groups: one group for each side of the Cerrado. The populations showed varying levels of admixture, with the greatest admixture evident in populations located toward central Brazil. CONCLUSIONS: In C. fissilis, genetic diversity is structured according to geography: the Atlantic range and the Chiquitano range each harbor a genealogical lineage. Interfertility and varying levels of admixture between lineages provide strong evidence that the lineages evolved under geographic, but not genetic, isolation. Admixture is of recent origin, owing to population expansion. Cedrela fissilis shares this dual pattern of distribution of genetic diversity with other phylogenetically unrelated taxa that are typically associated with seasonal forests. PMID- 26838367 TI - [Serious infections in patients with rheumatoid arthritis]. PMID- 26838368 TI - [Immune response to Mycobacterium tuberculosis]. AB - Infections with Mycobacterium tuberculosis (MTB) induce complex immune responses involving an orchestrated interplay of innate and adaptive immune mechanisms. Why the immune system fails to eradicate the pathogen and at best achieves control of infection in the latent stage, still remains an unsolved mystery even more than 100 years after the discovery of MTB by Robert Koch. This article provides an overview of the current state of the art in the constantly evolving field of tuberculosis (TB) immunology. This review focuses on a change of paradigm proposing that in the latent stage MTB is anything but dormant and that latent TB is not merely a state of bacterial stasis but a state of dynamic bacterial and immunological equilibrium. The understanding of these dynamics is crucial for the development of new drugs against MTB as well as vaccines that aim to provide effective protection against the disease. PMID- 26838369 TI - Multiple causes of an unexpected malaria outbreak in a high-transmission area in Madagascar. AB - BACKGROUND: The malaria burden in Madagascar dropped down last decade, largely due to scale-up of control measures. Nevertheless, a significant rise of malaria cases occurred in 2011-2012 in two regions of the rainy South-Eastern Madagascar, where malaria is considered as mesoendemic and the population is supposed to be protected by its acquired immunity against Plasmodium. A multidisciplinary investigation was conducted in order to identify the causes of the outbreak. METHODS: In March 2012, a cross-sectional study was conducted in 20 randomly selected clusters, involving the rapid diagnostic testing of all >=6 month-old members of households and a questionnaire about socio-demographic data and exposure to malaria control interventions. Changes in environmental conditions were evaluated by qualitative interview of local authorities, climatic conditions were evaluated by remote-sensing, and stock outs of malaria supplies in health facilities were evaluated by quantitative means. Two long-lasting insecticidal nets (LLINs) were sampled in each cluster in order to evaluate their condition and the remanence of their insecticidal activity. The entomological investigation also encompassed the collection Anopheles vectors in two sites, and the measure of their sensitivity to deltamethrin. RESULTS: The cross-sectional survey included 1615 members of 440 households. The mean Plasmodium infection rate was 25.6 % and the mean bed net use on the day before survey was 71.1 %. The prevalence of Plasmodium infections was higher in 6-14 year-old children (odds ratio (OR) 7.73 [95 % CI 3.58-16.68]), in rural areas (OR 6.25 [4.46-8.76]), in poorest socio-economic tercile (OR 1.54 [1.13-2.08]), and it was lower in individuals sleeping regularly under the bed net (OR 0.51 [0.32-0.82]). Stock outs of anti-malarial drugs in the last 6 months have been reported in two third of health facilities. Rainfalls were increased as compared with the three previous rainy seasons. Vectors collected were sensitive to pyrethroids. Two years after distribution, nearly all LLINs collected showed a loss of physical integrity and insecticide activity, CONCLUSIONS: Increased rainfall, decreasing use and reduced insecticide activity of long-lasting insecticide-treated nets, and drug shortages may have been responsible for, or contributed to, the outbreak observed in South-Eastern Madagascar in 2011-2012. Control interventions for malaria elimination must be sustained at the risk of triggering harmful epidemics, even in zones of high transmission. PMID- 26838370 TI - Paracrine effects of TLR4-polarised mesenchymal stromal cells are mediated by extracellular vesicles. AB - Mesenchymal stromal cells (MSCs) are adult stem cells able to give rise to bone, cartilage and fat cells. In addition, they possess immunomodulatory and immunosuppressive properties that are mainly mediated through secretion of extracellular vesicles (EVs). In a previous issue of Journal of Translational Medicine, Ti and colleagues demonstrated that preconditioning of MSCs with bacterial lipopolysaccharides results in secretion of EVs that can polarise macrophages towards anti-inflammatory M2 phenotype. Moreover, the authors suggest that EVs of lipopolysaccharide (LPS)-treated MSCs are superior to EVs of untreated MSCs concerning their ability to support wound healing. Our commentary critically discusses parallel efforts of other laboratories to generate conditioned media from stem cells for therapeutic applications, and highlights impact and significance of the study of Ti et al. Finally, we summarise its limitations and spotlight areas that need to be addressed to better define the underlying molecular mechanisms. PMID- 26838371 TI - Control of electronic transport in graphene by electromagnetic dressing. AB - We demonstrated theoretically that the renormalization of the electron energy spectrum near the Dirac point of graphene by a strong high-frequency electromagnetic field (dressing field) drastically depends on polarization of the field. Namely, linear polarization results in an anisotropic gapless energy spectrum, whereas circular polarization leads to an isotropic gapped one. As a consequence, the stationary (dc) electronic transport in graphene strongly depends on parameters of the dressing field: A circularly polarized field monotonically decreases the isotropic conductivity of graphene, whereas a linearly polarized one results in both giant anisotropy of conductivity (which can reach thousands of percents) and the oscillating behavior of the conductivity as a function of the field intensity. Since the predicted phenomena can be observed in a graphene layer irradiated by a monochromatic electromagnetic wave, the elaborated theory opens a substantially new way to control electronic properties of graphene with light. PMID- 26838373 TI - Risk factors and impact of non-Aspergillus mold infections following allogeneic HCT: a CIBMTR infection and immune reconstitution analysis. PMID- 26838372 TI - Circulating tumor cell counts/change for outcome prediction in patients with extensive-stage small-cell lung cancer. AB - AIMS: As data on the use of circulating tumor cells (CTCs) to predict patient outcomes in extensive-stage small-cell lung cancer (ES-SCLC) remain inconclusive, we investigated the clinical value of CTC determination in an open-label, multicenter study of 91 patients with newly diagnosed ES-SCLC. MATERIALS & METHODS: Blood CTC counts were determined using the CellSearch(r) system at baseline, after the second cycle of chemotherapy, and on disease progression. RESULTS & CONCLUSION: Following the second cycle of treatment, CTC numbers and the change in CTCs were strong, significant and independent indicators for both progression-free survival and overall survival in ES-SCLC. The CTC change was associated with both refractory disease (response to initial therapy <=3 months) and sensitive disease (response to initial therapy >3 months). PMID- 26838374 TI - A compact high resolution electrospray ionization ion mobility spectrometer. AB - Electrospray is a commonly used ionization method for the analysis of liquids. An electrospray is a dispersed nebular of charged droplets produced under the influence of a strong electrical field. Subsequently, ions are produced in a complex process initiated by evaporation of neutral solvent molecules from these droplets. We coupled an electrospray ionization source to our previously described high resolution ion mobility spectrometer with 75 mm drift tube length and a drift voltage of 5 kV. When using a tritium source for chemical gas phase ionization, a resolving power of R=100 was reported for this setup. We replaced the tritium source and the field switching shutter by an electrospray needle, a desolvation region with variable length and a three-grid shutter for injecting ions into the drift region. Preliminary measurements with tetraalkylammonium halides show that the current configuration with the electrospray ionization source maintains the resolving power of R=100. In this work, we present the characterization of our setup. One major advantage of our setup is that the desolvation region can be heated separately from the drift region so that the temperature in the drift region stays at room temperature even up to desolvation region temperatures of 100 degrees C. We perform parametric studies for the investigation of the influence of temperature on solvent evaporation with different ratios of water and methanol in the solvent for different analyte substances. Furthermore, the setup is operated in negative mode and spectra of bentazon with different solvents are presented. PMID- 26838375 TI - Chiral cyclodextrin-modified micellar electrokinetic chromatography and chemometric techniques for green tea samples origin discrimination. AB - Catechins and methylxanthines were determined in 92 green tea (GT) samples originating from Japan and China by using micellar electrokinetic chromatography with the addition of (2-hydroxypropyl)-beta-cyclodextrin. GT samples showed high concentrations of (-)-epigallocatechin gallate and caffeine, with (-) epigallocatechin, (-)-epicatechin gallate and (-)-epicatechin in relevant content and (+)-catechin, (-)-catechin and theobromine in much lower amounts. The amount of all the considered compounds was higher for Chinese GTs, with the exception of (-)-epicatechin gallate. Pattern recognition methods were applied to discriminate GTs according to geographical origin, which is an important factor to determine quality and reputation of a commercial tea product. Data analysis was performed by principal component analysis and hierarchical cluster analysis as exploratory techniques. Linear discriminant analysis and quadratic discriminant analysis were utilized as discrimination techniques, obtaining a very good rate of correct classification and prediction. PMID- 26838376 TI - A rhodamine B-based fluorescent sensor toward highly selective mercury (II) ions detection. AB - This work presented the design, syntheses and photophysical properties of a rhodamine B-based fluorescence probe, which exhibited a sensitive and selective recognition towards mercury (II). The chemosensor RA (Rhodamine- amide- derivative) contained a 5-aminoisophthalic acid diethyl ester and a rhodamine group, and the property of spirolactone of this chemosensor RA was detected by X ray crystal structure analyses. Chemosensor RA afforded turn-on fluorescence enhancement and displayed high brightness for Hg(2+), which leaded to the opening of the spirolactone ring and consequently caused the appearance of strong absorption at visible range, moreover, the obvious and characteristic color changed from colorless to pink was observed. We envisioned that the chemosensor RA exhibited a considerable specificity with two mercury (II) ions which was attributed to the open of spirolactone over other interference metal ions. PMID- 26838377 TI - Automated evaluation of protein binding affinity of anti-inflammatory choline based ionic liquids. AB - In this work, an automated system for the study of the interaction of drugs with human serum albumin (HSA) was developed. The methodology was based on the quenching of the intrinsic fluorescence of HSA by binding of the drug to one of its binding sites. The fluorescence quenching assay was implemented in a sequential injection analysis (SIA) system and the optimized assay was applied to ionic liquids based on the association of non-steroidal anti-inflammatory drugs with choline (IL-API). In each cycle, 100 uL of HSA and 100 uL of IL-API (variable concentration) were aspirated at a flow rate of 1 mL min(-1) and then sent through the reaction coil to the detector where the fluorescence intensity was measured. In the optimized conditions the effect of increasing concentrations of choline ketoprofenate and choline naproxenate (and respective starting materials: ketoprofen and naproxen) on the intrinsic fluorescence of HSA was studied and the dissociation constants (Kd) were calculated by means of models of drug-protein binding in the equilibrium. The calculated Kd showed that all the compounds bind strongly to HSA (Kd<100 umol L(-1)) and that the use of the drugs in the IL format does not affect or can even improve their HSA binding. The obtained results were compared with those provided by a conventional batch assay and the relative errors were lower than 4.5%. The developed SIA methodology showed to be robust and exhibited good repeatability in all the assay conditions (rsd<6.5%). PMID- 26838378 TI - Retrospective screening of pesticide metabolites in ambient air using liquid chromatography coupled to high-resolution mass spectrometry. AB - A new methodology for the retrospective screening of pesticide metabolites in ambient air was developed, using liquid chromatography coupled to Orbitrap high resolution mass spectrometry (UHPLC-HRMS), including two systematic workflows (i) post-run target screening (suspect screening) and (ii) non-target screening. An accurate-mass database was built and used for the post-run screening analysis. The database contained 240 pesticide metabolites found in different matrixes such as air, soil, water, plants, animals and humans. For non-target analysis, a "fragmentation-degradation" relationship strategy was selected. The proposed methodology was applied to 31 air samples (PM10) collected in the Valencian Region (Spain). In the post-target analysis 34 metabolites were identified, of which 11 (3-ketocarburan, carbofuran-7-phenol, carbendazim, desmethylisoproturon, ethiofencarb-sulfoxide, malaoxon, methiocarb-sulfoxide, N-(2-ethyl-6 methylphenyl)-L-alanine, omethoate, 2-hydroxy-terbuthylazine, and THPAM) were confirmed using analytical standards. The semiquantitative estimated concentration ranged between 6.78 and 198.31 pg m(-3). Likewise, two unknown degradation products of malaoxon and fenhexamid were elucidated in the non-target screening. PMID- 26838379 TI - Interval ridge regression (iRR) as a fast and robust method for quantitative prediction and variable selection applied to edible oil adulteration. AB - A novel quantitative prediction and variable selection method called interval ridge regression (iRR) is studied in this work. The method is performed on six data sets of FTIR, two data sets of UV-vis and one data set of DSC. The obtained results show that models built with ridge regression on optimal variables selected with iRR significantly outperfom models built with ridge regression on all variables in both calibration (6 out of 9 cases) and validation (2 out of 9 cases). In this study, iRR is also compared with interval partial least squares regression (iPLS). iRR outperfomed iPLS in validation (insignificantly in 6 out of 9 cases and significantly in one out of 9 cases for p<0.05). Also, iRR can be a fast alternative to iPLS, especially in case of unknown degree of complexity of analyzed system, i.e. if upper limit of number of latent variables is not easily estimated for iPLS. Adulteration of hempseed (H) oil, a well known health beneficial nutrient, is studied in this work by mixing it with cheap and widely used oils such as soybean (So) oil, rapeseed (R) oil and sunflower (Su) oil. Binary mixture sets of hempseed oil with these three oils (HSo, HR and HSu) and a ternary mixture set of H oil, R oil and Su oil (HRSu) were considered. The obtained accuracy indicates that using iRR on FTIR and UV-vis data, each particular oil can be very successfully quantified (in all 8 cases RMSEP<1.2%). This means that FTIR-ATR coupled with iRR can very rapidly and effectively determine the level of adulteration in the adulterated hempseed oil (R(2)>0.99). PMID- 26838380 TI - Preparation of Cu(2+)-mediated magnetic imprinted polymers for the selective sorption of bovine hemoglobin. AB - In this work, a novel Cu(2+)-mediated core-shell bovine hemoglobin imprinted superparamagnetic polymers were synthesized. First, carboxyl group directly functionalized Fe3O4 nanoparticles were produced by a facile one-pot hydrothermal method. Next, copper ions were introduced to chelate with carboxyl groups and further bonded with template bovine hemoglobin as co-functional monomer. Then, functional monomers 3-aminopropyltriethoxylsilane and octyltrimethoxysilane were adopted to form the thin polymer layers. Finally, after removal of the templates, the imprinting shells with specific recognition cavities for bovine hemoglobin were obtained on Fe3O4 nanoparticles. The resultant molecularly imprinted polymers have high adsorption capacity and satisfactory selectivity for bovine hemoglobin with the help of copper ions. The obtained magnetic nanomaterials were characterized by transmission electron microscopy, Fourier-transform infrared spectra, X-ray diffraction, and vibrating sample magnetometer. The measurements demonstrated that the as-synthesized nanomaterials exhibited good dispersion, high crystallinity, and satisfactory superparamagnetic properties. The feasibility of this method was further confirmed by using the imprinted nanomaterials to specifically extract bovine hemoglobin from real bovine blood samples. PMID- 26838381 TI - Microwave assisted one-pot synthesis of graphene quantum dots as highly sensitive fluorescent probes for detection of iron ions and pH value. AB - Recently, carbon nanomaterials have received considerable attention as fluorescent probes owing to their low toxicity, water solubility and stable photochemical properties. However, the development of graphene quantum dots (GQDs) is still on its early stage. In this work, GQDs were successfully synthesized by one-step microwave assisted pyrolysis of aspartic acid (Asp) and NH4HCO3 mixture. The as-prepared GQDs exhibited strongly blue fluorescence with high quantum yield up to 14%. Strong fluorescence quenching effect of Fe(3+) on GQDs can be used for its high selectivity detection among of general metal ions. The probe exhibited a wide linear response concentration range (0-50 MUM) to Fe(3+) and the limit of detection (LOD) was calculated to be 0.26 MUM. In addition, GQDs are also sensitive to the pH value in the range from 2 to 12 indicating a great potential as optical pH sensors. More importantly, the GQDs possess lower cellular toxicity and high photostability and can be directly used as fluorescent probes for cell imaging. PMID- 26838382 TI - The novel voltammetric method for determination of hesperetin based on a sensitive electrochemical sensor. AB - A highly sensitive voltammetric sensor, based on reduced graphene oxide on SWCNTs modified glassy carbon electrode (GCE), was constructed and used for sensitive detection of hesperetin. The electrochemical behavior of hesperetin at this sensor was investigated systematically and a novel voltammetric method for determination of hesperetin was proposed. The redox characters of hesperetin was discussed in detail and a reasonable reaction mechanism was proposed also. As the analytical method, the response currents were linear relationship with the hesperetin concentrations in the range of 5.0 * 10(-8) to 3.0 * 10(-6) mol L-(1), with a detection limit of 2.0 * 10(-8) mol L(-1) (S/N=3). The method was also applied successfully to detect hesperetin in biological samples and Chinese herbal medicine Flos buddlejae with satisfactory results. PMID- 26838383 TI - Sensitive methanol sensor based on PMMA-G-CNTs nanocomposites deposited onto glassy carbon electrodes. AB - A new series of polymethyl methacrylate-graphene-carbon nanotubes crossbred nanocomposites in the form of PMMA-G-CNTs has been synthesized using simple dissolution procedure in organic media. The desired nanocomposites have been prepared using different loading (2 ~ 30%) from consequently mixed GNPs/CNTs ratio and confirmed by various characterization techniques utilized to corroborate the assembly of these new hybrid series including X-ray diffraction analysis, Fourier transform infrared spectroscopy and scanning electron microscopy. The PMMA-G-CNTs nanocomposites were deposited on flat glassy carbon electrodes (GCE) to result in a sensor that has a fast response toward methanol in the phosphate buffer phase. Features including high sensitivity, low-sample volume, reliability, reproducibility, ease of integration, long-term stability, and enhanced electrochemical responses are investigated. The calibration plot is linear (r(2)=0.9895) over the 1.0 nmol L(-1) to 10.0 mmol L(-1) methanol concentration ranges. The sensitivity and detection limit is 13.491 uA cm(-2) mmol L(-2) and 0.39 +/- 0.1 nmol L(-1) (at a signal-to-noise-ratio, SNR of 3), respectively. With such excellent features of analytical parameters, the developed sensor provides a new strategy for determination of methanol in biomedical and environmental analytes with satisfactory results. PMID- 26838384 TI - Microfluidic chip-based silver nanoparticles aptasensor for colorimetric detection of thrombin. AB - In this paper, a colorimetric silver nanoparticles aptasensor (aptamer-AgNPs) was developed for simple and straightforward detection of protein in microfluidic chip. Surface-functionalized microfluidic channels were employed as the capture platform. Then the mixture of target protein and aptamer-AgNPs were injected into the microfluidic channels for colorimetric detection. To demonstrate the performance of this detection platform, thrombin was chosen as a model target protein. Introduction of thrombin could form a sandwich-type complex involving immobilized AgNPs. The amount of aptamer-AgNPs on the complex augmented along with the increase of the thrombin concentration causing different color change that can be analyzed both by naked eyes and a flatbed scanner. This method is featured with low sample consumption, simple processes of microfluidic platform and straightforward colorimetric detection with aptamer-AgNPs. Thrombin at concentrations as low as 20pM can be detected using this aptasensor without signal amplification. This work demonstrated that it had good selectivity over other proteins and it could be a useful strategy to detect other targets with two affinity binding sites for ligands as well. PMID- 26838385 TI - High resolution mass spectrometry coupled with multivariate data analysis revealing plasma lipidomic alteration in ovarian cancer in Asian women. AB - Ovarian cancer (OC) is the most common cause of death from gynecologic malignancies in women. The identification of reliable diagnostic biomarkers for the early detection of this deadly disease is critical for reducing the mortality rate of OC. Plasma lysophosphatidic acid (LPA) levels were increased from OC patients vs. healthy controls. Therefore, lipidomics may represent an excellent developing prospect for the discovery of diagnostic biomarkers of OC. In this study, a nontargeted lipidomics approach based on ultra performance liquid chromatography-electrospray ionization-QTOF-mass spectrometry (UPLC-ESI-QTOF-MS) combined with multivariate data analysis, including principal component analysis (PCA) and (orthogonal) partial least squared discriminant analysis [(O)PLS-DA] was applied for the investigation of potential diagnostic biomarkers in plasma of OC patients. Patients with OC could be distinguished from healthy individuals and patients with benign gynecological tumor disease by this method, which shows a significant lipid perturbation in this disease. With the assistance of high resolution and high accuracy of MS and MS/MS data, the potential markers including lysophosphatidylcholines (LPCs), phosphatidylcholines (PCs) and triacylglycerols (TGs) with specific fatty acid chains, were identified. Interestingly, LPCs were up-regulated and PCs and TGs were down-regulated, compared OC group with benign tumor and normal control groups, and the glycerophospholipid metabolism emerged as a key pathway, in particular, the phospholipase A2 (PLA2) enzyme activity, that was disregulated in the disease. This study may provide new insight into underlying mechanisms for OC and proves that MS-based lipidomics is a powerful method in discovering new potential clinical biomarkers for diseases. PMID- 26838386 TI - An optimized and validated (1)H NMR method for the quantification of alpha-pinene in essentials oils. AB - The authenticity and composition of commercial essential oils requires strict quality control. Due to the importance of alpha-pinene containing essential oils, a rapid and efficient method for quantification of this terpene in oils of eucalyptus, pink pepper and turpentine using (1)H NMR was developed and validated. All evaluated parameters (selectivity, linearity, accuracy/precision, repeatability, robustness, stability of analyte and internal standard in solutions) showed satisfactory results. The limit of detection (LOD) and limit of quantification (LOQ) were 0.1 and 2.5mg respectively. These values indicated that alpha-pinene was detected in 35 mg samples containing at least 0.3% of this compound. In addition, a minimum of 8% of alpha-pinene in the sample was required for quantification. Furthermore, the standard deviations found in the (1)H NMR methodology were less than 1% and were lower than those obtained by gas chromatographic analysis. Statistical tests have shown that the results obtained by (1)H NMR methodology are similar to those obtained by GC-FID technique using external and internal standardization and normalization within 95% confidence. R&R values lower than 10% have shown that all the methods are appropriate and the (1)H NMR method is suitable for quantification of alpha-pinene in samples of essential oils since this method possessed the smallest R&R (1.81) value. PMID- 26838387 TI - Solvent-assistant self-assembly of an AIE+TICT fluorescent Schiff base for the improved ammonia detection. AB - Solvent-assistant self-assembly of an AIE+TICT fluorescent Schiff base into one dimensional nanofilaments has been developed. The orientation of the assemblies can be controlled by a simple dewetting process: the filaments are interweaved when the self-assembly process is performed on a horizontal substrate, while tilting the substrate to a tiny angle results in the formation of highly oriented ones with long-range order as verified by microscopic examination. The compound shows remarkable fluorescent response to ammonia gas based on a TICT-LE transition. The self-assembled film presents higher detection sensitivity compared with the non-assembled test paper: the former enables 4.75 times faster response time and 6.86 times lower detection limit than the latter. Furthermore, the former demonstrates better selectivity toward ammonia gas in the presence of various organic amines. The sensing devices also enjoy the advantage of cyclic utilization. The fluorescence of the fumed devices can be converted back into the original state when they are heated at 100 degrees C for 5 min, as thermal treatment can desorb the ammonia gas that adsorbed in the sensing devices. PMID- 26838388 TI - New approach to the fast screening of plant oil samples for F-, Cl-, Br- and S organic compounds on the trace level. AB - The fast method of the simultaneous determination of F(-), Cl(-), Br(-) and SO4(2 ) anions in the deionized water on the trace level by ion chromatography using thorough cleaning of respective water containers, 10 MUM NaHCO3 water solution as eluent, short Metrohm (50 * 4 mm) separation column and a large water volume injection is proposed. Calculated detection limits are 10(-9)-10(-8)% depending on the element. The method for the fast screening of plant oil samples for the total fluorine-, chlorine-, bromine- and sulfur-organic compounds content (calculated for the respective elements) on the trace level is developed. It is based on the high temperature combustion of oil sample in oxygen flow, absorption of the conversion products in deionized water and whole absorbate volume analysis for F(-), Cl(-), Br(-) and SO4(2-) anions, corresponding to the respective elements, using the developed method of these anions analysis by ion chromatography. The samples of soya, olive, sunflower and cotton seed oil were analyzed. The method detection limits (for 1mg sample) were 2 * 10(-6)%, 2 * 10( 6)%, 5 * 10(-6)% and 5 * 10(-6)% for fluorine, chlorine, bromine and sulfur, respectively. The relative standard deviation was <= 15%. The method gives the compressed information about the total content of all target and nontarget fluorine-, chlorine-, bromine- and sulfur-organic compounds in plant oils. PMID- 26838389 TI - Upconversion luminescence tracking of gene delivery via multifunctional nanocapsules. AB - The real-time fluorescence tracking of gene delivery is very important as it helps to figure out how a vector enters a cell and also to follow its fate within the cell interior. Lanthanide-doped upconversion nanoparticles (UCNPs) have shown great potential in biomedical applications in virtue of their unique optical and biological properties. Herein, we report a simple and versatile strategy to fabricate a multifunctional nanocapsule for effective gene delivery and real-time luminescence tracking. The hydrophobic UCNPs were modified by positively charged amphiphilic polymer together with polyethylene glycol-poly(lactic-co-glycolic acid) (PEG-PLGA) polymer, affording biocompatible nanocapsules with high gene loading capacity and good stability. Red UC luminescence of UCNPs are able to track the delivery of nanocapsules in cells without background fluorescence interference, in the meantime, the green fluorescence of green fluorescence protein (GFP) expressed by the pDNA could subtly monitor the gene transfection efficacy. The results demonstrated that our nanocapsule has ideal biocompatibility, satisfactory gene loading capacity and great bioimaging ability, which is promising for imaging guided cell therapy and gene engineering. PMID- 26838391 TI - A handheld laser-induced fluorescence detector for multiple applications. AB - In this paper, we present a compact handheld laser-induced fluorescence (LIF) detector based on a 450 nm laser diode and quasi-confocal optical configuration with a total size of 9.1 * 6.2 * 4.1 cm(3). Since there are few reports on the use of 450 nm laser diode in LIF detection, especially in miniaturized LIF detector, we systematically investigated various optical arrangements suitable for the requirements of 450 nm laser diode and system miniaturization, including focusing lens, filter combination, and pinhole, as well as Raman effect of water at 450 nm excitation wavelength. As the result, the handheld LIF detector integrates the light source (450 nm laser diode), optical circuit module (including a 450 nm band-pass filter, a dichroic mirror, a collimating lens, a 525 nm band-pass filter, and a 1.0mm aperture), optical detector (miniaturized photomultiplier tube), as well as electronic module (including signal recording, processing and displaying units). This detector is capable of working independently with a cost of ca. $2000 for the whole instrument. The detection limit of the instrument for sodium fluorescein solution is 0.42 nM (S/N=3). The broad applicability of the present system was demonstrated in capillary electrophoresis separation of fluorescein isothiocyanate (FITC) labeled amino acids and in flow cytometry of tumor cells as an on-line LIF detector, as well as in droplet array chip analysis as a LIF scanner. We expect such a compact LIF detector could be applied in flow analysis systems as an on-line detector, and in field analysis and biosensor analysis as a portable universal LIF detector. PMID- 26838390 TI - Magnetic solid-phase extraction of phthalate esters (PAEs) in apparel textile by core-shell structured Fe3O4@silica@triblock-copolymer magnetic microspheres. AB - In this paper, novel core-shell structured magnetic Fe3O4/silica nanocomposites with triblock-copolymer grafted on their surface (Fe3O4@SiO2@MDN) were successfully fabricated by combining a sol-gel method with a seeded aqueous-phase radical copolymerization approach. Owing to the excellent characteristics of the strong magnetic responsivity, outstanding hydrophilicity and abundant pi-electron system, the obtained core-shell structured microspheres showed great potential as a magnetic solid phase extraction (MSPE) adsorbent. Several kinds of phthalate esters (PAEs) were selected as model analytes to systematically evaluate the applicability of adsorbents for extraction followed by gas chromatography-mass spectrometry (GC-MS) analyses. Various parameters, including adsorbents amounts, adsorption time, species of eluent, and desorption time were optimized. Under the optimized conditions, Validation experiments such as recovery, reproducibility, and limit of detection were carried on and showed satisfactory results. The analysis method showed excellent linearity with a wide range of 0.2-10mg/kg (R(2)>0.9974) and low limits of detection (LOD) of 0.02-0.09 mg/kg (S/N=3). Ultimately, the novel magnetic adsorbents were successfully employed to detect the PAEs in apparel textile samples. And the results indicated that this novel approach brought forward in the present work offered an attractive alternative for rapid, efficient and sensitive MSPE for PAEs compounds. PMID- 26838392 TI - Investigation of chemical modifiers for the direct determination of arsenic in fish oil using high-resolution continuum source graphite furnace atomic absorption spectrometry. AB - High-resolution continuum source graphite furnace atomic absorption spectrometry (HR-CS GF AAS) has been applied for the development of a method for the determination of total As in fish oil samples using direct analysis. The method does not use any sample pretreatment, besides dilution with 1-propanole, in order to decrease the oil viscosity. The stability and sensitivity of As were evaluated using ruthenium and iridium as permanent chemical modifiers and palladium added in solution over the sample. The best results were obtained with ruthenium as the permanent modifier and palladium in solution added to samples and standard solutions. Under these conditions, aqueous standard solutions could be used for calibration for the fish oil samples diluted with 1-propanole. The pyrolysis and atomization temperatures were 1400 degrees C and 2300 degrees C, respectively, and the limit of detection and characteristic mass were 30 pg and 43 pg, respectively. Accuracy and precision of the method have been evaluated using microwave-assisted acid digestion of the samples with subsequent determination by HR-CS GF AAS and ICP-MS; the results were in agreement (95% confidence level) with those of the proposed method. PMID- 26838393 TI - Novel molecularly-imprinted solid-phase microextraction fiber coupled with gas chromatography for analysis of furan. AB - This study combined a molecularly-imprinted polymer with headspace solid-phase microextraction (HS-SPME). Preparation of molecularly-imprinted polymer is not effective for volatile compounds. To overcome this limitation, pyrrole was chosen as a template for the preparation of the furan-imprinted polymer. The holes in the synthesized polymer were suitable for furan adsorption because the chemical structure of pyrrole is similar to that of furan. The extraction properties of the fiber to furan were examined using an HS-SPME device coupled with gas chromatography-flame ionization detection (GC-FID) and gas chromatography-mass spectrometry (GC-MS). The effects of the extraction parameters of exposure time, sampling temperature, and salt concentration on extraction efficiency were studied. Satisfactory reproducibility was obtained for extractions from spiked water samples at RSD<7.5% (n=5). The calibration graphs were linear at 0.5-100 ng ml(-1) and the detection limit for furan was 0.042 ng ml(-1). The fabricated fiber was successfully applied for headspace extraction of furan from tap water and canned tuna as shown by GC-MS analysis. PMID- 26838394 TI - Label free molecular sexing of monomorphic birds using infrared spectroscopic imaging. AB - The absence of sexual dimorphism in many birds often makes sex determination difficult. In particular immature birds and adults of monomorphic species show no external sex characteristics. Molecular techniques based on DNA hybridization or polymerase chain reaction (PCR) are standard methods for sex identification. However, these methods are expensive and time consuming procedures and require special sample preparation. Noninvasive methods for a rapid determination of bird's gender are of increasing importance for ornithologists, breeders as well as for successful captive-breeding programs. Fourier transform infrared (FT-IR) spectroscopy is one such technique that can provide gender specific information. In this study, using the example of domestic pigeons (Columba livia f. dom.) we demonstrate that only a small amount of the feather pulp is needed to determine the gender. FT-IR spectroscopic images of feather pulp suspensions were recorded in transmission mode. Principal component analysis (PCA) and linear discriminant analysis (LDA) were performed to identify the sex. The gender related information are described by 2nd and 4th principal component principle component (PC). The 2nd PC represents different amounts of proteins while the 4th PC shows variations within the amide I and amide II bands as well as in the region of phosphate vibrations of nucleic acids. Blood cells of male pigeons exhibit a significantly higher amount of proteins and nucleic acids than those of female pigeons. Feather pulp samples of male species were assigned with 100% accuracy. Seven from eight female samples were assigned correctly while one sample could not be classified. This study demonstrates that the sex of domestic pigeons can be accurately and and rapidly identified by infrared spectroscopic imaging. PMID- 26838395 TI - Design and fabrication of optical chemical sensor for detection of nitroaromatic explosives based on fluorescence quenching of phenol red immobilized poly(vinyl alcohol) membrane. AB - The present study developed a new optical chemical sensor for detection of nitroaromatic explosives in liquid phase. The method is based on the fluorescence quenching of phenol red as fluorophore in a poly(vinyl alcohol) (PVA) membrane in the presence of nitroaromatic explosives as quenchers, e.g., 2,4,6 trinitrotoluene (TNT), 2,4-dinitrotoluene (2,4-DNT), 4-nitrotoluene (4-NT), 2,4,6 trinitrobenzene (TNB), and nitrobenzene (NB). For chemical immobilization of phenol red in PVA, phenol red reacted with formaldehyde to produce hydroxymethyl groups and then attached to PVA membrane through the hydroxymethyl groups. The optical sensor showed strong quenching of nitroaromatic explosives. A Stern Volmer graph for each explosive was constructed and showed that the range of concentration from 5.0 * 10(-6) to 2.5 * 10(-4) mol L(-1) was linear for each explosive and sensitivity varied as TNB >TNT>2,4-DNT>NB>4-NT. The response time of the sensor was within 1 min. The proposed sensor showed good reversibility and reproducibility. PMID- 26838396 TI - Validated method for the determination of perfluorinated compounds in placental tissue samples based on a simple extraction procedure followed by ultra-high performance liquid chromatography-tandem mass spectrometry analysis. AB - Xenobiotic exposure during pregnancy is inevitable. Determination of perfluorinated compounds (PFCs), chemicals described as environmental contaminants by Public Health Authorities due to their persistence, bioaccumulation and toxicity, is a challenge. In the present work, a method based on a simplified sample treatment involving freeze-drying, solvent extraction and dispersive clean-up of the extracts using C18 sorbents followed by an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis was developed and validated for the determination of five perfluorinated carboxylic acids (C4-C8) and perfluorooctane sulfonate (PFOS) in placental tissue samples. The most influential parameters affecting the extraction method and clean-up were optimized using Design of Experiments (DOE). The method was validated using matrix-matched calibration. Found limits of detection (LODs) ranged from 0.03 to 2 ng g(-1) and limits of quantification (LOQs) from 0.08 to 6 ng g(-1), while inter- and intra-day variability was under 14% in all cases. Recovery rates for spiked samples ranged from 94% to 113%. The method was satisfactorily applied for the determination of compounds in human placental tissue samples collected at delivery from 25 randomly selected women. PMID- 26838397 TI - Direct analysis in real time mass spectrometry of potential by-products from homemade nitrate ester explosive synthesis. AB - This work demonstrates the coupling of direct analysis in real time (DART) ionization with time-of-flight mass spectrometry (MS) in an off-axis configuration for the trace detection and analysis of potential partially nitrated and dimerized by-products of homemade nitrate ester explosive synthesis. Five compounds relating to the synthesis of nitroglycerin (NG) and pentaerythritol tetranitrate (PETN) were examined. Deprotonated ions and adducts with molecular oxygen, nitrite, and nitrate were observed in the mass spectral responses of these compounds. A global optimum temperature of 350 degrees C for the by-products investigated here enabled single nanogram to sub nanogram trace detection. Matrix effects were examined through a series of mixtures containing one or more compounds (sugar alcohol precursors, by-products, and/or explosives) across a range of mass loadings. The explosives MS responses experienced competitive ionization in the presence of all by-products. The magnitude of this influence corresponded to both the degree of by-product nitration and the relative mass loading of the by-product to the explosive. This work provides a characterization of potential by-products from homemade nitrate ester synthesis, including matrix effects and potential challenges that might arise from the trace detection of homemade explosives (HMEs) containing impurities. Detection and understanding of HME impurities and complex mixtures may provide valuable information for the screening and sourcing of homemade nitrate ester explosives. PMID- 26838398 TI - A quantum dot-spore nanocomposite pH sensor. AB - A new quantum dot (QD)-based pH sensor design is investigated. The sensor is synthesized based on the self-assembly of green QDs onto treated spores to form QD@spore nanocomposites. The nanocomposites are characterized using laser scanning confocal microscopy, transmission electron microscope, and fluorescence spectroscopy, among others. Fluorescence measurements showed that these nanocomposites are sensitive to pH in a broad pH range of 5.0-10.0. The developed pH sensors have been satisfactorily applied for pH estimation of real samples and are comparable with those of the commercial assay method, indicating the potential practical application of the pH sensors. PMID- 26838399 TI - Quantitative structure-retention relationships applied to development of liquid chromatography gradient-elution method for the separation of sartans. AB - QSRR are mathematically derived relationships between the chromatographic parameters determined for a representative series of analytes in given separation systems and the molecular descriptors accounting for the structural differences among the investigated analytes. Artificial neural network is a technique of data analysis, which sets out to emulate the human brain's way of working. The aim of the present work was to optimize separation of six angiotensin receptor antagonists, so-called sartans: losartan, valsartan, irbesartan, telmisartan, candesartan cilexetil and eprosartan in a gradient-elution HPLC method. For this purpose, ANN as a mathematical tool was used for establishing a QSRR model based on molecular descriptors of sartans and varied instrumental conditions. The optimized model can be further used for prediction of an external congener of sartans and analysis of the influence of the analyte structure, represented through molecular descriptors, on retention behaviour. Molecular descriptors included in modelling were electrostatic, geometrical and quantum-chemical descriptors: connolly solvent excluded volume non-1,4 van der Waals energy, octanol/water distribution coefficient, polarizability, number of proton-donor sites and number of proton-acceptor sites. Varied instrumental conditions were gradient time, buffer pH and buffer molarity. High prediction ability of the optimized network enabled complete separation of the analytes within the run time of 15.5 min under following conditions: gradient time of 12.5 min, buffer pH of 3.95 and buffer molarity of 25 mM. Applied methodology showed the potential to predict retention behaviour of an external analyte with the properties within the training space. Connolly solvent excluded volume, polarizability and number of proton-acceptor sites appeared to be most influential paramateres on retention behaviour of the sartans. PMID- 26838400 TI - Polyaniline/graphene quantum dot-modified screen-printed carbon electrode for the rapid determination of Cr(VI) using stopped-flow analysis coupled with voltammetric technique. AB - Polyaniline/graphene quantum dots (PANI/GQDs) were used to modify a screen printed carbon electrode (SPCE) in a flow-based system. A method for rapidly determining the Cr(VI) concentrations by using stopped-flow analysis has been developed using an Auto-Pret system coupled with linear-sweep voltammetry using the PANI/GQD-modified SPCE. The GQDs, synthesized in a botton-up manner from citric acid, were mixed with aniline monomer in an optimized ratio. The mixture was injected into an electrochemical flow cell in which electro-polymerization of the aniline monomer occurred. Under conditions optimized for determining Cr(VI), wide linearity was obtained in the range of 0.1-10 mg L(-1), with a detection limit of 0.097 mg L(-1). For a sample volume of 0.5 m L, the modified SPCE can be used continuously with a sample-throughput of more than 90 samples per hour. In addition, this proposed method was successfully applied to mineral water samples with acceptable accuracy, and the quantitative agreement was accomplished in deteriorated Cr-plating solutions with a standard traditional method for Cr(VI) detection. PMID- 26838401 TI - Chemometric evaluation of Cd, Co, Cr, Cu, Ni (inductively coupled plasma optical emission spectrometry) and Pb (graphite furnace atomic absorption spectrometry) concentrations in lipstick samples intended to be used by adults and children. AB - A method was developed for determining the concentrations of Cd, Co, Cr, Cu, Ni and Pb in lipstick samples intended to be used by adults and children using inductively coupled plasma optical emission spectrometry (ICP OES) and graphite furnace atomic absorption spectrometry (GF AAS) after treatment with dilute HNO3 and hot block. The combination of fractional factorial design and Desirability function was used to evaluate the ICP OES operational parameters and the regression models using Central Composite and Doehlert designs were calculated to stablish the best working condition for all analytes. Seventeen lipstick samples manufactured in different countries with different colors and brands were analyzed. Some samples contained high concentrations of toxic elements, such as Cr and Pb, which are carcinogenic and cause allergic and eczematous dermatitis. The maximum concentration detected was higher than the permissible safe limits for human use, and the samples containing these high metal concentrations were intended for use by children. Principal component analysis (PCA) was used as a chemometrics tool for exploratory analysis to observe the similarities between samples relative to the metal concentrations (a correlation between Cd and Pb was observed). PMID- 26838402 TI - Large volume preconcentration and determination of nanomolar concentrations of iron in seawater using a renewable cellulose 8-hydroquinoline sorbent microcolumn and universal approach of post-column eluate utilization in a Lab-on-Valve system. AB - We report on a Lab-On-Valve (LOV) configuration for analyte preconcentration from milliliter sample volumes using confluent mixing in the holding coil for in-line addition of loading buffer. The system was applied to the spectrophotometric determination of iron(II) in acidified seawater using 1,10-phenanthroline as color reagent. A cellulose-based chelating sorbent containing 8-hydroxyquinoline was used for the first time in LOV and excellent retention behavior and loading capacity were found. The flow system employs a syringe pump for handling all solutions (sorbent suspension, loading buffer, water, eluent, and color reagent) and a peristaltic pump for sample propulsion and includes a fit-for-purpose 14 cm long detection glass flow cell and a bubble trap for in-line carrier degasification. Advantage was taken of the LOV flow-through port to keep the eluted analytes for re-aspiration for subsequent chromogenic reaction. In effect, a universal analyzer configuration and preconcentration procedure was developed, which is combinable with other analytes, sorbents, and reagents. Among the studied parameters were the compositions, pH, volumes, and flow rates of loading buffer, eluent, and color reagent, as well as the microcolumn size, repeatability, and system stability. Reproducibility of 4.1% RSD over the entire working range, a LOD of down to 5 nmol L(-1), sampling frequency of 12h(-1), and linearity up to 1 umol L(-1) for 3.3 mL of sample were obtained and applicability to real samples was demonstrated. It was proven that both Fe(III) and Fe(II) were retained and yielded similar recovery and sensitivity values. The method was applied to coastal seawater samples and spiking experiments yielded recovery values close to 100%. PMID- 26838403 TI - Development of a biodegradable sensor platform from gold coated zein nanophotonic films to detect peanut allergen, Ara h1, using surface enhanced raman spectroscopy. AB - Peanuts are among the most common food allergies, which may result in life threatening reactions in certain people. For this reason, it is very important to monitor the presence of peanuts in the food system. Biosensors are an emerging way of detecting allergen proteins. In this research, we present a surface enhanced Raman spectroscopy (SERS) technique to detect the main allergen protein, Ara h1. The sensors were biodegradable and made out of a corn protein, zein. Nanophotonic structures on zein films consisted of gold coated pyramid structures. It was found that both detection and quantification was possible by using a statistical clustering technique principal component analysis (PCA). An optimization in data processing yielded the result that baseline correction and shorter data collection times were needed in order to successfully cluster data. The limit of detection was found to be 0.14 mg/ml. Furthermore, specificity of the sensor was provided by functionalizing the surface with monoclonal antibodies of Ara h1. Antibody functionalization, and Ara h1 capturing was tested and identified by also utilizing PCA analysis. As a proof-of-concept, this study showed that a biodegradable platform can be used in detection of a peanut allergen protein, Ara h1, using surface enhanced Raman spectroscopy. PMID- 26838404 TI - Determination of chloramphenicol, thiamphenicol and florfenicol in milk and honey using modified QuEChERS extraction coupled with polymeric monolith-based capillary liquid chromatography tandem mass spectrometry. AB - A poly(lauryl methacrylate-co-methacrylic acid-co-ethylene glycol dimethacrylate) [LMA-MAA-EDMA] monolithic column was used to simultaneously determine amphenicol antibiotics (chloramphenicol/CAP, thiamphenicol/TAP, and florfenicol/FF) in milk and honey samples by capillary liquid chromatography tandem mass spectrometry (LC MS/MS). QuEChERS (quick, easy, cheap, effective, rugged, and safe) method was optimized for sample pretreatment. Good linearity (0.1-15 ng g(-1)) and extraction recoveries (95.8-100.2% and 95.6-99.3% for milk and honey samples, respectively; n=3) with minor matrix effect (? 5% ion suppression) were obtained. Limits of detection were estimated at 0.02-0.045 ng g(-1). Good intra-day/inter day precision (0.2-9.1%/0.3-8.7%) and accuracy (90.5-110.0%/93.4-109.3%) were achieved. With more than 200 analyses of real samples, no noticeable carry-over and deterioration of separation efficiency were observed using the monolithic column. The applicability of the developed QuEChERS-capillary LC-MS/MS method was demonstrated by determining the occurrence of CAP, TAP, and FF in various milk and honey samples. PMID- 26838405 TI - Determination of boron in produced water using the carminic acid assay. AB - Using the carminic acid assay, we determined the concentration of boron in oilfield waters. We investigated the effect of high concentrations of salts and dissolved metals on the assay performance. The influence of temperature, development time, reagent concentration, and water volume was studied. Ten produced and flowback water samples of different origins were measured, and the method was successfully validated against ICP-MS measurements. In water-stressed regions, produced water is a potential source of fresh water for irrigation, industrial applications, or consumption. Therefore, boron concentration must be determined and controlled to match the envisaged waste water reuse. Fast, precise, and onsite measurements are needed to minimize errors introduced by sample transportation to laboratories. We found that the optimum conditions for our application were a 5:1 mixing volume ratio (reagent to sample), a 1 g L(-1) carminic acid concentration in 99.99% sulfuric acid, and a 30 min reaction time at ambient temperature (20 degrees C to 23 degrees C). Absorption values were best measured at 610 nm and 630 nm and baseline corrected at 865 nm. Under these conditions, the sensitivity of the assay to boron was maximized while its cross sensitivity to dissolved titanium, iron, barium and zirconium was minimized, alleviating the need for masking agents and extraction methods. PMID- 26838406 TI - One pot synthesis of intriguing fluorescent carbon dots for sensing and live cell imaging. AB - We report a simple one-pot synthesis of highly fluorescent carbon dots (CDs) via modified hydrothermal (MHT) treatment of alkaline solution of dopamine and cysteine. These CDs (lambdaex=320 nm, lambdaem=390 nm, and quantum yield ~ 5.1%) are of ~ 2-3 nm in diameter. Further attempt of synthesizing CDs in some common water-miscible solvents ends up the fact that the MHT product from acetone medium is nonfluorescent. However, CDs, produced in aqueous medium, are so stable that they can be dried as a deliverable solid (WCD) without any alteration of fluorescing property if reversibly dispersed in water. Fluorescence of WCD is quenched selectively in acetone. Quenching occurs presumably due to the disruption of radiative recombination along with the hindrance in quantum confinement of the emissive energy traps to the particle surface. Successive quenching of fluorescence of WCD in different acetone concentration admixed in water paves the way to selective acetone sensing (LOD=8.75 * 10(-7) M). The synthesized CDs (in aqueous medium) are cytocompatible and are efficient fluorescent probe for cell imaging. Only living cells are recognized exclusively from fluorescence imaging leaving aside dead cells, while cells are treated with CDs. PMID- 26838407 TI - Inorganic arsenic speciation in natural mineral drinking waters by flow-through anodic stripping chronopotentiometry. AB - A simple and inexpensive method for chemical speciation of inorganic As in natural mineral drinking waters by using anodic stripping chronopotentiometry (ASCP) in an electrochemical flow-through cell with an Au wire as the working electrode was described in the present work. The presented method is an attractive alternative to laborious and time-consuming procedures requiring pre separation of various forms of As before their detection by other flow-through and non flow-through stripping methods. The limits of detection were found to be 0.42 ug L(-1) for As(III) and 0.55 ug L(-1) for As(V), obtained at the deposition potentials of -350 mV and -1600 mV, respectively. The accuracy of the method was assessed by the spiking-and-recovery experiments for particular water samples and the recoveries found, being in range from 99% to 105% for As(III) and from 104% to 106% for As(V), respectively, were quantitative. The proposed method was successfully applied to speciation analysis of inorganic As in water samples with a high content of Cu. PMID- 26838408 TI - A comparison of devices using thermal desorption for mercury speciation in solids. AB - The goal of this work is to emphasize the reliability of the thermal desorption technique in identifying mercury species. The analysis of mercury species in solids is essential for assessing the risk of disposal or re-use of mercury contaminated materials. This study evaluates the accuracy and reliability of thermal desorption as a technique for identifying mercury species by means of different thermo-desorption devices. For this purpose, mercury species present in samples related with coal utilization processes were identified. Three devices were compared for analyzing samples free of carbon or with a low carbon content (fly ashes, gypsums and soils), and a new equipment was developed to analyze samples with a high carbon content (coal). In spite of the fact that the first three devices employ different experimental conditions (i.e., heating rate, gas flow and carrier gas), the mercury species identified in the samples were comparable in all cases. The need for new equipment for mercury speciation in materials containing carbon was a consequence of interferences produced from the pyrolysis products of the organic matter. The new device consists of two furnaces and two gas inlets to allow thermal oxidation of organic pyrolysis products and the identification of mercury species in carbonaceous samples. This new approach offers the application of thermal desorption to mercury speciation in all types of materials contaminated with mercury. PMID- 26838409 TI - Optimization of in-cell accelerated solvent extraction technique for the determination of organochlorine pesticides in river sediments. AB - Organochlorine pesticides (OCPs) are ubiquitous environmental contaminants with adverse impacts on aquatic biota, wildlife and human health even at low concentrations. However, conventional methods for their determination in river sediments are resource intensive. This paper presents an approach that is rapid and also reliable for the detection of OCPs. Accelerated Solvent Extraction (ASE) with in-cell silica gel clean-up followed by Triple Quadrupole Gas Chromatograph Mass Spectrometry (GCMS/MS) was used to recover OCPs from sediment samples. Variables such as temperature, solvent ratio, adsorbent mass and extraction cycle were evaluated and optimized for the extraction. With the exception of Aldrin, which was unaffected by any of the variables evaluated, the recovery of OCPs from sediment samples was largely influenced by solvent ratio and adsorbent mass and, to some extent, the number of cycles and temperature. The optimized conditions for OCPs extraction in sediment with good recoveries were determined to be 4 cycles, 4.5 g of silica gel, 105 degrees C, and 4:3 v/v DCM: hexane mixture. With the exception of two compounds (alpha-BHC and Aldrin) whose recoveries were low (59.73 and 47.66% respectively), the recovery of the other pesticides were in the range 85.35-117.97% with precision <10% RSD. The method developed significantly reduces sample preparation time, the amount of solvent used, matrix interference, and is highly sensitive and selective. PMID- 26838410 TI - Label-free and dynamic evaluation of cell-surface epidermal growth factor receptor expression via an electrochemiluminescence cytosensor. AB - A label-free electrochemiluminescence (ECL) cytosensor was developed for dynamically evaluating of epidermal growth factor receptor (EGFR) expression on MCF-7 cancer cells based on the specific recognition of epidermal growth factor (EGF) with its receptor (EGFR). EGF-cytosensor was fabricated by in-situ electro polymerization of polyaniline as substrate, using CdS quantum dots (CdS QDs) as ECL probe and gold nanoparticles (AuNPs) as a carrier for loading of EGF. AuNPs and CdS QDs were jointly attached on polyaniline surface to provide a sensitive and stable sensing interface, as well as a simple and label-free mode for ECL assay. Electron microscopy, atomic force microscopy (AFM) and electrochemical methods were employed to characterize the multilayer construction process of the sensing interface. The proposed EGF-cytosensor exhibited excellent analytical performance for MCF-7 cancer cells, ranging from 12 to 1.2 * 10(6) cells mL(-1), with a low detection limit of 12 cells mL(-1). Also, it was successfully applied in evaluating EGFR expression of cells surface, which was stimulated by some inhibitors or activator, and the results were confirmed by using flow cytometry and laser scanning confocal microscopy analysis. The proposed ECL cytosensor has potential applications in monitoring the dynamic variation of receptor molecules expression on cell surfaces in response to external stimulation by drugs and screening anti-cancer therapeutic agents. PMID- 26838411 TI - Designed synthesis of Graphene @titania @mesoporous silica hybrid material as size-exclusive metal oxide affinity chromatography platform for selective enrichment of endogenous phosphopeptides. AB - In this work, a novel size-exclusive metal oxide affinity chromatography (SE MOAC) platform was built for phosphoproteome research. The operation for preparing graphene @titania @mesoporous silica nanohybrids (denoted as G@TiO2@mSiO2) was facile and easy to conduct by grafting titania nanoparticles on polydopamine (PD)-covered graphene, following a layer of mesoporous silica was coated on the outermost layer. The G@TiO2@mSiO2 nanohybrids exhibited high sensitivity with a low detection limit of 5 amol/MUL (a total amount of 1 fmol) and high selectivity for phosphopeptides at a mass ratio of phosphopeptides to non-phosphopeptides (1:1000). The size-exclusive capability of the nanohybrids were also demonstrated by enriching the phosphopeptides from the mixture of Bovine Serum Albumin (BSA), alpha-casein, and beta-casein digests with a high mass ratio (beta-casein digests: alpha-casein: BSA, 1:500:500), which was attributed to the large surface area and ordered mesoporous channels. In addition, the G@TiO2@mSiO2 nanohybrids were employed to capture the endogenous phosphopeptides from human serum successfully. PMID- 26838412 TI - Hydrophobic interface controlled electrochemical sensing of nitrite based on one step synthesis of polyhedral oligomeric silsesquioxane/reduced graphene oxide nanocomposite. AB - In this paper, we report a novel hydrophobic interface controlled electrochemical sensing of nitrite based on polyhedral oligomeric silsesquioxane/ reduced graphene oxide nanocomposite (POSS/rGO). The POSS/rGO is prepared by one step hydrothermal synthesis method, and characterized by transmission electron microscopy (TEM), fourier transform infrared spectroscopy (FT-IR), Zeta-potential measurement analyzer, electrochemical impedance spectroscopy (EIS) and zero current potential method respectively. Then the POSS/rGO composite is used to fabricate electrochemical sensor for nitrite detection. According to experimental results, it is found that under control of hydrophobic force, the current peak will be shifted to lower potential (0.72 V) and the possible reason has been analyzed in manuscript. In addition, the POSS/rGO based sensor also has wide linear range (0.5 MUM to 120 mM), low detection limit (0.08 MUM) and good selectivity. In a word, the hydrophobic force controlled detection in this paper will provide a new platform for electrochemical sensing. PMID- 26838413 TI - Polyaniline/cyclodextrin composite coated stir bar sorptive extraction combined with high performance liquid chromatography-ultraviolet detection for the analysis of trace polychlorinated biphenyls in environmental waters. AB - A novel polyaniline/alpha-cyclodextrin (PANI/alpha-CD) composite coated stir bar was prepared by sol-gel process for the analysis of polychlorinated biphenyls (PCBs) in this work. The preparation reproducibility of the PANI/alpha-CD-coated stir bar was good, with relative standard deviations (RSDs) ranging from 2.3% to 3.7% (n=7) and 2.0% to 3.8% (n=7) for bar to bar and batch to batch, respectively. Based on it, a novel method of PANI/alpha-CD-coated stir bar sorptive extraction (SBSE) followed by high performance liquid chromatography ultraviolet (HPLC-UV) detection was developed for the determination of trace PCBs in environmental waters. To obtain the best extraction performance for target PCBs, several parameters affecting SBSE, such as extraction time, stirring rate, and ionic strength were investigated. Under optimal experimental conditions, the limits of detection (LODs) of the proposed method for seven PCBs were in the range of 0.048-0.22 MUg/L, and the RSDs were 5.3-9.8% (n=7, c=1 MUg/L). Enrichment factors (EFs) ranging from 39.8 to 68.4-fold (theoretical EF, 83.3 fold) for target analytes were achieved. The proposed method was successfully applied for the determination of seven target PCBs in Yangtze River water and East Lake water, and the recoveries were in the range of 73.0-120% for the spiked East Lake water samples and 82.7-121% for the spiked Yangtze River water samples, respectively. PMID- 26838414 TI - Selective detection of 2,4,6-trinitrophenol based on a fluorescent nanoscale bis(8-hydroxyquinoline) metal complex. AB - The reliable and accurate detection of explosives such as 2,4,6-trinitrophenol (TNP) and 2,4,6-trinitrotoluene (TNT) is in high demand for homeland security and public safety. Although extremely high sensitivity towards TNT has been demonstrated, detection of TNP remains a challenge. In this work, a fluorescent nanoscale complex composed of bis(8-hydroxyquinoline) and Al(3+) ions has been prepared, characterized and applied in detection of TNP. This complex exhibits the ability to sense the nitro explosive TNP via a fluorescence quenching mechanism with high selectivity. A simple paper test system for the rapid monitoring of TNP was also investigated. The results show that Bhq-Al is a quite ideal sensing material for trace-level detection of TNP. PMID- 26838415 TI - Sulfur and nitrogen binary doped carbon dots derived from ammonium thiocyanate for selective probing doxycycline in living cells and multicolor cell imaging. AB - A novel sulfur and nitrogen binary doped carbon dots (S,N-CDs) was synthesized by one-step manner through the hydrothermal treatment of citric acid (CA) and ammonium thiocyanate, and the procedures for biomedical applications, including probing doxycycline in living cells and multicolor cell imaging were developed. The obtained S,N-CDs are stable in aqueous solution, possess a very high quantum yield (QY, 74.15%) and good photostability. The fluorescence of S,N-CDs can be specifically quenched by doxycycline, providing a convenient turn-off assay of doxycycline. This assay shows a wide linear detection range from 0.08 to 60 MUM with a low detection limit of 20 nM. The present method also displays a good selectivity. More importantly, the S,N-CDs have an excellent biocompatibility and low cytotoxicity, allowing the multicolor cell imaging and doxycycline detection in living cells. Consequently, the developed doxycycline methods is facile, low cost, biocompatible, sensitive and selective, which may hold the potential applications in the fields of food safety and environmental monitoring, as well as cancer therapy and related mechanism research. PMID- 26838416 TI - Analytical approach to determining human biogenic amines and their metabolites using eVol microextraction in packed syringe coupled to liquid chromatography mass spectrometry method with hydrophilic interaction chromatography column. AB - Analysis of biogenic amines (BAs) in different human samples provides insight into the mechanisms of various biological processes, including pathological conditions, and thus may be very important in diagnosing and monitoring several neurological disorders and cancerous tumors. In this work, we developed a simple and fast procedure using a digitally controlled microextraction in packed syringe (MEPS) coupled to liquid chromatography mass spectrometry (LC-MS) method for simultaneous determination of biogenic amines, their precursors and metabolites in human plasma and urine samples. The separation of 12 low molecular weight and hydrophilic molecules with a wide range of polarities was achieved with hydrophilic interaction chromatography (HILIC) column without derivatization step in 12 min. MEPS was implemented using the APS sorbent in semi-automated analytical syringe (eVol((r))) and small volume of urine and plasma samples, 5 0uL and 100 MUL, respectively. We evaluated important parameters influencing MEPS efficiency, including stationary phase selection, sample pH and volume, number of extraction cycles, and washing and elution volumes. In optimized MEPS conditions, the analytes were eluted by 3 * 50 MUL of methanol with 0.1% formic acid. The chromatographic separation of analytes was performed on XBridge AmideTM BEH analytical column (3.0mm * 100 mm, 3.5 um) using gradient elution with mobile phase consisting of phase A: 10mM ammonium formate buffer in water pH 3.0 and phase B: 10mM ammonium formate buffer in acetonitrile pH 3.0. The LC-HILIC-MS method was validated and, in optimum conditions, presented good linearity in concentration range within 10-2000 ng/mL for all the analytes with a determination coefficient (r(2)) higher than 0.999 for plasma and urine samples. Method recovery ranged within 87.6-104.3% for plasma samples and 84.2-98.6% for urine samples. The developed method utilizing polar APS sorbent along with polar HILIC column was applied for simultaneous bioanalysis of trace amounts of polar endogenous biogenic amines in real human urine and plasma samples. PMID- 26838417 TI - Phosphorylation regulates proteolytic efficiency of TEV protease detected by a 5(6)-carboxyfluorescein-pyrene based fluorescent sensor. AB - TEV protease is of great importance for in vitro and in vivo site-specific cleavage of proteins. The proteolytic efficiency of TEV protease is often regulated by mutation of the substrate, which is irreversible and hard to be modulated. Herein, a facile and reversible method, based on phosphorylation in the substrate, is developed to regulate the cleavage capability of TEV protease. Phosphorylation at P3 tyrosine hinders the recognition of TEV protease to the substrate by using a robust fluorescent protease sensor. Moreover, the phosphate group can be easily removed by alkaline phosphatases for recovering the proteolytic efficiency of TEV protease. Additionally, 5(6)-carboxyfluorescein and pyrene have been used as high-efficiency mutual fluorophore-quencher pair in the peptide-based protease sensor for the first time, which provides a chance to simultaneously monitor the cleavage process in two respective fluorescence channels. Further studies indicated both dynamic and static components contributing to the mutual quenching system. The phosphorylation-regulated TEV protease proteolysis system can be used in conditional cleavage of protein or peptide tag. PMID- 26838418 TI - A novel voltammetric sensor based on poly(l-Citrulline)/SWCNTs composite film modified electrode for sensitive determination of picroside II. AB - A novel voltammetric sensor was constructed by simple dripping single-walled carbon nanotubes (SWCNTs) on to the glass carbon electrode (GCE) firstly and electro-polymerizing L-Citrulline film subsequently. The resulting poly(L Citrulline)/SWCNTs/GCE showed a significant voltammetric response to picroside II due to the synergistic effect of SWCNTs and poly(L-Citrulline) film. The first electroanalytical method of picroside II was proposed with detection linear range from 8.0 * 10(-8) to 5.0 * 10(-6) mol L(-1) and a detection limit of 3 * 10(-8) mol L(-1). The high sensitivity, selectivity and long-term stability made the sensor suitable for the determination of picroside II. Moreover, based on the systematically investigation and some kinetics parameters calculated in the experimentation, the reaction mechanism of picroside II at the poly(L Citrulline)/SWCNTs modified GCE was obtained reliably. Lastly, the proposed sensor was used for the determination of picroside II in real sample with satisfactory results. This work promoted the potential applications of amino acid materials and SWCNTs in electro-chemical sensors. PMID- 26838419 TI - Evaluating the potential of LC coupled to three alternative detection systems (ESI-IT, APCI-TOF and DAD) for the targeted determination of triterpenic acids and dialcohols in olive tissues. AB - Herewith the development of a rapid and powerful LC methodology (with three different detectors) is presented to determine triterpenic acids and dialcohols in extracts from Olea europaea tissues (olive skin, pulp and leaves). After the proper optimization of the LC, DAD and MS conditions and the comprehensive characterization of the behavior of each analyte in ESI and APCI (with accurate m/z signals and, in ESI, with MS/MS data too), the method was fully validated. DAD, ESI-IT MS and APCI-QTOF MS were used as detection systems to give different alternatives to carry out the accurate determination of these analytes, evaluate their analytical performance, advantages and drawbacks, and check whether the quantitative results achieved by the three platforms were in good agreement. ESI IT MS gave the lowest detection limits (3-455 MUg/L) followed by APCI-QTOF MS (22 408 MUg/L); in contrast, DAD (83-600 MUg/L) had the widest dynamic range. The RSD values for inter-day repeatability were found below 11.82% in all the cases. No statistically significant differences were found among the quantitative results from the three detectors. Olive leaves showed the highest concentration levels of ursolic acid (1.8 mg/g), erythrodiol (1.6 mg/g) and uvaol (1.2mg/g), whereas the olive skin was the richest matrix in terms of maslinic (80 mg/g), betulinic (0.20mg/g), and oleanolic (26 mg/g) acids. Concentration values of triterpenic acids were established by first time for skinless olive pulp, and were found around 65, 1.2, 55 and 4.4 MUg/g for maslinic, betulinic, oleanolic and ursolic acids, respectively. PMID- 26838420 TI - Prediction of specialty coffee cup quality based on near infrared spectra of green coffee beans. AB - The growing global demand for specialty coffee increases the need for improved coffee quality assessment methods. Green bean coffee quality analysis is usually carried out by physical (e.g. black beans, immature beans) and cup quality (e.g. acidity, flavour) evaluation. However, these evaluation methods are subjective, costly, time consuming, require sample preparation and may end up in poor grading systems. This calls for the development of a rapid, low-cost, reliable and reproducible analytical method to evaluate coffee quality attributes and eventually chemical compounds of interest (e.g. chlorogenic acid) in coffee beans. The aim of this study was to develop a model able to predict coffee cup quality based on NIR spectra of green coffee beans. NIR spectra of 86 samples of green Arabica beans of varying quality were analysed. Partial least squares (PLS) regression method was used to develop a model correlating spectral data to cupping score data (cup quality). The selected PLS model had a good predictive power for total specialty cup quality and its individual quality attributes (overall cup preference, acidity, body and aftertaste) showing a high correlation coefficient with r-values of 90, 90,78, 72 and 72, respectively, between measured and predicted cupping scores for 20 out of 86 samples. The corresponding root mean square error of prediction (RMSEP) was 1.04, 0.22, 0.27, 0.24 and 0.27 for total specialty cup quality, overall cup preference, acidity, body and aftertaste, respectively. The results obtained suggest that NIR spectra of green coffee beans are a promising tool for fast and accurate prediction of coffee quality and for classifying green coffee beans into different specialty grades. However, the model should be further tested for coffee samples from different regions in Ethiopia and test if one generic or region-specific model should be developed. PMID- 26838421 TI - Polydopamine-assisted partial hydrolyzed poly(2-methyl-2-oxazolinze) as coating for determination of melamine in milk by capillary electrophoresis. AB - Nitrogen-rich melamine (66% by mass) had been found to be illegally adulterated to milk products and animal feed in order to increase the apparent protein content, and ingestion of melamine may lead to the formation of kidney stones. Hence, the development of reliable analytical methods for the monitoring of melamine in milk products is necessary. The common methods for melamine analysis in milk products are performed via GC-MS or HPLC, however, these procedures require a large of organic solvent and several pretreatment steps. In this study, a new and facile approach was developed to modify a fused-silica capillary inner surface based on poly(dopamine) (PDA) and partial hydrolyzed poly(2-methyl-2 oxazoline) (PMOXA-EI) mixed coating, which was used to determine the melamine in milk powder quantitatively by capillary electrophoresis with ultraviolet (CE-UV) detection with simple analytes pretreatment. Firstly, the influences of the molecular mass of poly(2-methyl-2-oxazoline) (PMOXA), the hydrolysis degree of PMOXA, and the concentration ratio of DA to PMOXA-EI on the separation properties of a mixture of four basic proteins (cytochrome c, lysozyme, ribonuclease A, and alpha-chymotrypsinogen A) were studied in detail. As a consequence, fast and efficient separation of four proteins was obtained using PDA/PMOXA1k-EI0.4 coating (once coating). Then, a modified facile coating workflow was carried out to acquire a novel twice coating (i.e. PDA/PMOXA1k-EI0.4+PMOXA1k-EI0.4 coated capillary) for highly sensitive and stable analysis of melamine. Under the optimal conditions, the linear response of melamine concentration ranged from 6.25 to 100 ug/mL with high correlation coefficient of 0.9910, and the limit of detection (LOD) for melamine was 0.097 ug/mL. The minimum amount of melamine determined in milk powder with our proposed method was 4 mg/kg. The recoveries and relative standard deviations (RSDs) were 92.13-102.47%, 92.22-100.30%, 2.07 4.98%, and 2.43-3.77%, respectively for the intraday and interday analysis. After being used continually for 45 days, the PDA/PMOXA1k-EI0.4+PMOXA1k-EI0.4 coated capillary could be still used to detect the melamine from milk powder, with the recovery from 91.85% to 106.14%. The technique developed in this study provides a simple and relatively sensitive method for determination of melamine in milk powder. PMID- 26838422 TI - Preparation of molecularly imprinted polymers using theanine as dummy template and its application as SPE sorbent for the determination of eighteen amino acids in tobacco. AB - In this paper, a novel dummy template molecularly imprinted polymer (DMIP) based on a vinyl-SiO2 microspheres surface for the simultaneous selective recognition and enrichment of 18 amino acids was prepared via a surface molecular imprinting technique using theanine as a dummy template. Compared to the imprinted polymers prepared using traditional polymerization techniques, the obtained DMIPs exhibited a regular spherical shape and were relatively monodisperse. The maximal sorption capacity (Qmax) of the resulting DMIPs for the 18 amino acids was up to 1444.3 mg g(-1). A kinetic binding study showed that the sorption capacity reached 85.40% of Qmax in 25 min and sorption equilibrium at 30 min. The imprint factors of the sorbents ranged from 2.86 to 6.9 for the 18 amino acids, which indicated that the DMIP sorbents have high selectivity. An HPLC-UV method for the simultaneous determination of 18 amino acids in tobacco and tobacco smoke was developed using the DMIPs as sorbents for solid phase extraction (SPE) in the sample pretreatment procedure. Under the optimum experimental conditions, the materials had enrichment factors of up to 200 for the amino acids, and the recoveries of the 18 amino acids in tobacco smoke were in the range from 79% to 104% with relative standard deviations of less than 7.4%. It indicated that the obtained DMIP sorbents could specifically recognize the amino acids from complicated samples. PMID- 26838423 TI - An enhanced cerium(IV)-rhodamine 6G chemiluminescence system using guest-host interactions in a lab-on-a-chip platform for estimating the total phenolic content in food samples. AB - Two chemiluminescence-microfluidic (CL-MF) systems, e.g., Ce(IV)-rhodamine B (RB) and Ce(IV)-rhodamine 6G (R6G), for the determination of the total phenolic content in teas and some sweeteners were evaluated. The results indicated that the Ce(IV)-R6G system was more sensitive in comparison to the Ce(IV)-RB CL system. Therefore, a simple (CL-MF) method based on the CL of Ce(IV)-R6G was developed, and the sensitivity, selectivity and stability of this system were evaluated. Selected phenolic compounds (PCs), such as quercetin (QRC), catechin (CAT), rutin (RUT), gallic acid (GA), caffeic acid (CA) and syringic acid (SA), produced analytically useful chemiluminescence signals with low detection limits ranging from 0.35 nmol L(-1) for QRC to 11.31 nmol L(-1) for SA. The mixing sequence and the chip design were crucial, as the sensitivity and reproducibility could be substantially affected by these two factors. In addition, the anionic surfactant (i.e., sodium dodecyl sulfate (SDS)) can significantly enhance the CL signal intensity by as much as 300% for the QRC solution. Spectroscopic studies indicated that the enhancement was due to a strong guest-host interaction between the cationic R6G molecules and the anionic amphiphilic environment. Other parameters that could affect the CL intensities of the PCs were carefully optimized. Finally, the method was successfully applied to tea and sweetener samples. Six different tea samples exhibited total phenolic/antioxidant levels from 7.32 to 13.5 g per 100g of sample with respect to GA. Four different sweetener samples were also analyzed and exhibited total phenolic/antioxidant levels from 500.9 to 3422.9 mg kg(-1) with respect to GA. The method was selective, rapid and sensitive when used to estimate the total phenolic/antioxidant level, and the results were in good agreement with those reported for honey and tea samples. PMID- 26838424 TI - A "Turn-on-off-on" fluorescence switch based on quantum dots and gold nanoparticles for discriminative detection of ovotransferrin. AB - A novel strategy for ovotransferrin (OVT) detection by tracing the "on-off-on" fluorescence signals of quantum dots (QDs) and gold nanoparticles (AuNPs) utilizing fluorescence measurements were established in this article. The immune interaction between QDs-OVT and anti-OVT-AuNPs leads to drastic quenching (turning off) of the donor by a fluorescence resonance energy transfer (FRET) process. After the addition of free OVT, anti-OVT-AuNPs peel off from the QDs-OVT surface and bind to free OVT due to competitive immunoreactions, resulting in the restoration of the fluorescence intensity of QDs (turning on). Consequently, this process can be utilized for the selective detection of OVT via optical responses. Under optimal conditions, the fluorescence intensity of the system increased linearly with increasing concentrations of OVT from 0.05 to 3.8 MUg/mL. The limit of detection of OVT was 23.55 ng/mL. This method was applied to the analysis of OVT in egg powder samples. Furthermore, the strategy provided in this work could be conveniently followed to establish similar immunosensors for the rapid detection of other proteins with corresponding antibodies. PMID- 26838425 TI - Determination of selected parabens, benzophenones, triclosan and triclocarban in agricultural soils after and before treatment with compost from sewage sludge: A lixiviation study. AB - An accurate and sensitive method for the determination of selected EDCs in soil and compost from wastewater treatment plants is developed and validated. Five parabens, six benzophenone-UV filters and the antibacterials triclosan and triclocarban were selected as target analytes. The parameters for ultrasound assisted extraction were thoroughly optimized. After extraction, the analytes were detected and quantified using ultra-high performance liquid chromatography tandem mass spectrometry. Ethylparaben (ring-(13)C6 labelled) and deuterated benzophenone (BP-d10) were used as internal standards. The method was validated using matrix-matched calibration and recovery assays with spiked samples. The limits of detection ranged from 0.03 to 0.40 ng g(-1) and the limits of quantification from 0.1 to 1.0 ng g(-1), while precision in terms of relative standard deviation was between 9% and 21%. Recovery rates ranged from 83% to 107%. The validated method was applied for the study of the behavior of the selected compounds in agricultural soils treated and un-treated with compost from WWTP. A lixiviation study was developed in both agricultural soil and treated soil and first order kinetic models of their disappearance at different depths are proposed. The application of organic composts in the soil leads to an increase of the disappearance rate of the studied compounds. The lixiviation study also shows the risk of pollution of groundwater aquifers after disposal or waste of these EDCs in agricultural soils is not high. PMID- 26838427 TI - Spectrometric estimation of sample amount in aliquot for a direct solid sampling system and its application to the determination of trace impurities in silver nanoparticles by ETV-ICP-OES. AB - A method based on a tungsten boat furnace vaporiser, tungsten sample cuvettes, and an inductively coupled plasma (ICP) optical emission spectrometer has been developed for the direct determination of silicon, phosphorus, and sulphur in silver nanoparticles. The important point in the proposed method is that the entire sample in each batch is vaporised, which enables simultaneous measurement of the emission of not only the analyte but also the silver matrix. Furthermore, since the silver nanoparticles are sufficiently pure, the contribution of impurities to the sample amounts will be negligible. Therefore, this estimation is suitable for measuring the sample amount in each aliquot instead of the conventional weighing procedure using a microbalance; therefore, no tedious weighing procedures for estimating the sample amount introduced into the ETV device are needed. An additional advantage is that pretreatment and/or predigestion are unnecessary. The sample throughput is approximately 35 batches per hour. The detection limits of silicon, phosphorus, and sulphur in the silver nanoparticles (dry powder) are 15, 4.2, and 62 ug g(-1), respectively. Analytical results for various silver nanoparticles as both dry particles and in suspended solutions are described, and these values are compared to those obtained by conventional weighing with a microbalance. This methodology is useful for rapid screening and accurate analysis of silver nanoparticles, especially for industrial applications. PMID- 26838426 TI - Reusable potentiometric screen-printed sensor and label-free aptasensor with pseudo-reference electrode for determination of tryptophan in the presence of tyrosine. AB - Analysis of L-tryptophan (Trp) in biological samples has great importance for biomedical studies. Amino acid tyrosine (Tyr) that usually coexist with Trp in biological fluids can significantly interfere with reliable determination of Trp. In the current study, we demonstrate the development of two ultra-sensitive electrochemical sensor and label-free aptasensor for selective analysis of Trp in biological samples (i.e., cow's milk and human plasma, saliva and urine samples). In addition, without using AgCl/KCl, an Ag pseudo-reference screen printed electrode (Ag-PR-SPE) was exploited as a reference electrode. To prepare the engineered Trp sensor/aptasensor, a gold SPE was first modified with multiwall carbon nanotube (MWCNT-AuSPE) and then armed with Trp aptamer molecules (Apt MWCNT-AuSPE). The prepared sensors were characterized using constant current potentiometric stripping analysis (CC-PSA) and electrochemical impedance spectroscopy (EIS). The MWCNT-AuSPE and Apt-MWCNT-AuSPE were compared with respect to the linear detection range, limit of detection (LOD), accuracy, precision, repeatability. MWCNT-AuSPE and Apt-MWCNT-AuSPE demonstrate fast near Nernstian response for PSA of Trp over the concentration ranging from 1.0 * 10( 9) to 2.0 * 10(-4) mol L(-1) and 1.0 * 10(-11) to 1.0 * 10(-4) mol L(-1) with detection limits of 3.6 * 10(-10) mol L(-1) and 4.9 * 10(-12) mol L(-1), respectively. Common interfering species present in the biological fluids (i.e., tyrosine, uric acid, ascorbic acid) showed no effects on the determination of Trp using CC-PSA. MWCNT-AuSPE and Apt-MWCNT-AuSPE represented well reproducibility and great precision with relative standard deviation (RSD) of 2.9% and 5.3% respectively. In comparison with the MWCNT-AuSPE, Apt-MWCNT-AuSPE provided higher sensitivity, selectivity and accuracy of Trp detection in real samples. Based on these findings, we propose the developed Apt-MWCNT-AuSPE as a simple detection method for analysis of Trp in biological samples. PMID- 26838429 TI - Towards a zero-blank, preconcentration-free voltammetric method for iron analysis at picomolar concentrations in unbuffered seawater. AB - A method with negligible blank values for the determination of total iron at the ultratrace level in seawater has been optimized and validated exploring for the first time the performance and limitations of Adsorptive Cathodic Stripping Voltammetry (AdCSV) in non-buffered solutions. The method is based on the CSV determination of the Fe-dihydroxynaphthalene (DHN) complex using atmospheric oxygen to catalytically enhance the signal via hydrogen peroxide formation at the electrode/solution interface. The accumulation of hydroxyl ions, the by-product of the hydrogen peroxide formation, increased the pH in the diffusion layer in the absence of buffer bringing it to 9, the optimum for the analytical performance of the method. Voltammograms in UV digested seawater showed no stability or reproducibility drawbacks. The negligible, lower than 5pM, blank level, is due to the simplicity of the procedure requiring no sample manipulation and a maximum of three reagents only, necessarily the ligand DHN and a base only for those samples previously acidified to raise the pH to circumneutral values (here HCl and NH3 according to common trace metals protocols). These reagents do not require cleaning before use, further simplifying the overall procedure. Analysis of seawater previously acidified at pH ~1.5 with HCl and neutralized with ammonia showed interferences due to the buffering properties of the NH3/NH4Cl couple and the transient formation of a volatile electroactive interference that can be easily removed by simply allowing a set time before analysis. In general, the proposed method features several advantages, including high sample throughput, an excellent limit of detection at 12pM, minimum sample handling (no preconcentration or change of matrix is required), cost effectiveness and mainly a negligible blank. The method was successfully validated using open ocean consensus samples (SAFe D2 and S). PMID- 26838428 TI - Rapid and label-free detection of ochratoxin A and aflatoxin B1 using an optical portable instrument. AB - In this study, we report a novel assay for the combined on site detection of aflatoxin B1 (AFB1) and ochratoxin A (OTA), through a colorimetric biosensing system for AFB1 and a fluorimetric detection for OTA, exploiting the capability of the portable fibre optic spectrometer to perform both analyses. AFB1 was detected using the acetylcholinesterase (AChE) enzyme that is inhibited by this toxin, and the degree of inhibition was quantified by the Ellman's spectrophotometric method, obtaining a detection limit of 10 ug L(-1). OTA quantification was performed by monitoring its intrinsic fluorescence in methanol, reaching a detection limit of 0.1 ug L(-1). In order to successfully apply the analytical tool in the food analysis, immunoaffinity columns were used. Clean-up and quantification of both AFB1 and OTA in millet samples was obtained by HPLC-dedicated AflaOchra-Test HPLCTM (VicamTM) and Afla-OtaCLEANTM (LC-Tech) immunoaffinity columns, followed by absorption/fluorescence detection. Millet samples which were fortified with both OTA (50 ug kg(-1)) and AFB1 (20 ug kg( 1)), gave recovery values of 100 +/- 6% for OTA, and 110 +/- 10% for AFB1, using AflaOchra-Test HPLCTM. Single OTA clean-up and quantification in wine samples was obtained, using an OchraTest immunoaffinity column (VicamTM), reaching a detection limit of 0.3 ug L(-1) and recovery values between 80% and 120%. These results demonstrated the possibility of employing a single clean-up and a cost effective, and easy to use analytical system for both AFB1 and OTA detection at ug kg(-1) (ppb) level. Furthermore, in the case of positive samples, they could be analysed further, using standard chromatographic procedures, without any additional clean-up step, since the same extraction procedure of standard method is proposed in our method. PMID- 26838430 TI - A microfluidic cigarette smoke collecting platform for simultaneous sample extraction and multiplex analysis. AB - In this work, we report a novel microfluidic gas collecting platform aiming at simultaneous sample extraction and multiplex mass spectrometry (MS) analysis. An alveolar-mimicking elastic polydimethylsiloxane (PDMS) structures was designed to move dynamically driven by external pressure. The movement was well tuned both by its amplitude and rhythm following the natural process of human respiration. By integrating the alveolar units into arrays and assembling them to gas channels, a cyclic contraction/expansion system for gas inhale and exhale was successfully constructed. Upon equipping this system with a droplet array on the alveolar array surface, we were able to get information of inhaled smoke in a new strategy. Here, with cigarette smoke as an example, analysis of accumulation for target molecules during passive smoking is taken. Relationships between the breathing times, distances away from smokers and inhaled content of nicotine are clarified. Further, by applying different types of extraction solvent droplets on different locations of the droplet array, simultaneous extraction of nicotine, formaldehyde and caproic acid in sidestream smoke (SS) are realized. Since the extract droplets are spatially separated, they can be directly analyzed by MS which is fast and can rid us of all complex sample separation and purification steps. Combining all these merits, this small, cheap and portable platform might find wide application in inhaled air pollutant analysis both in and outdoors. PMID- 26838432 TI - A novel conductometric biosensor based on hexokinase for determination of adenosine triphosphate. AB - The paper presents a simple and inexpensive reusable biosensor for determination of the concentration of adenosine-5'-triphosphate (ATP) in aqueous samples. The biosensor is based on a conductometric transducer which contains two pairs of gold interdigitated electrodes. An enzyme hexokinase was immobilized onto one pair of electrodes, and bovine serum albumin-onto another pair (thus, a differential mode of measurement was used). Conditions of hexokinase immobilization on the transducer by cross-linking via glutaraldehyde were optimized. Influence of experimental conditions (concentration of magnesium ions, ionic strength and concentration of the working buffer) on the biosensor work was studied. The reproducibility of biosensor responses and operational stability of the biosensor were checked during one week. Dry storage at -18 degrees C was shown to be the best conditions to store the biosensor. The biosensor was successfully applied for measurements of ATP concentration in pharmaceutical samples. The proposed biosensor may be used in future for determination of ATP and/or glucose in water samples. PMID- 26838433 TI - Graphene-silica hybrid in efficient preconcentration of heavy metal ions via novel single-step method of moderate centrifugation-assisted dispersive micro solid phase extraction. AB - Novel nanoadsorbent of graphene-silica hybrid was synthesized via chemical vapor deposition (CVD) method. Graphene sheets were catalytically grown on a silica based substrate and after being characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM), their high efficacy in adsorption of metal ions (lead, cadmium, and chromium) was examined. It was found that the presence of silica within the G-SiO2 structure imparts an amphiphilic property to the hybrid that enables it to interact with both free and bounded metal ions present in the biological samples. Utilization of the innovative method of moderate centrifugation-assisted dispersive micro solid phase extraction (MCDuSPE) coupled with electrothermal atomic absorption spectrometry (ETAAS), not only facilitated absolute separation of the fabricated nanoadsorbent from the solvent, but also helped complete recovering of the scant volume of desorbed supernatant. Thus, microliter amount of desorption solvent can be regained completely by MCDuSPE method without sorbent loss. Various parameters affecting the extraction efficiency were investigated and admirable linearity from 0.012 to 12.5 ug L(-1) and favorable detection limits (LOD) could be recorded. Intra day precision (RSD, n=10) ranged from 3.1 to 3.8%, whereas inter day precision (RSD, n=5) ranged from 6.3 to 7.2%. PMID- 26838431 TI - A fluorescent immunochromatographic strip test using Quantum Dots for fumonisins detection. AB - A fluorescent immunochromatographic strip test (ICST) based on the use of Quantum Dots (QD) was developed and applied to detect fumonisins in maize samples. A limit of detection for fumonisin B1 of 2.8 ug L(-1) was achieved, with an analytical working range of 3-350 ug L(-1), corresponding to 30-3500 ug kg(-1) in maize flour samples, according with the extraction procedure. The time required to perform the analysis was 22 min, including sample preparation. Recovery values in the range from 91.4% to 105.4% with coefficients of variation not exceeding 5% were obtained for fortified and naturally contaminated maize flour samples. To evaluate the possible improvements due to the use of QD for ICST technology, we performed a direct comparison of the proposed QD-ICST to a gold nanoparticles- and a chemiluminescent-ICST previously developed for fumonisins detection, in which the same immunoreagents were employed. PMID- 26838434 TI - Direct and simultaneous quantification of ATP, ADP and AMP by (1)H and (31)P Nuclear Magnetic Resonance spectroscopy. AB - ATP, ADP and AMP are energy substances with vital biological significance. Based on the structural differences, a simple, rapid and comprehensive method has been established by (1)H and (31)P Nuclear Magnetic Resonance ((1)H-NMR and (31)P-NMR) spectroscopies. Sodium 3-(trimethylsilyl) propionate-2,2,3,3-d4 (TMSP) and anhydrous disodium hydrogen phosphate (Na2HPO4) were selected as internal standards for (1)H-NMR and (31)P-NMR, respectively. Those three compounds and corresponding internal standards can be easily distinguished both by (1)H-NMR and (31)P-NMR. In addition, they all have perfect linearity in a certain range: 0.1 100mM for (1)H-NMR and 1-75 mM for (31)P-NMR. To validate the precision of this method, mixed samples of different concentrations were measured. Recovery experiments were conducted in serum (91-113% by (1)H-NMR and 89-113% by (31)P NMR). PMID- 26838435 TI - Chromatographic behavior of 12 polar pteridines in hydrophilic interaction chromatography using five different HILIC columns coupled with tandem mass spectrometry. AB - Retention characteristic of 5 hydrophilic interaction chromatography (HILIC) columns, containing neutral and possibly negatively charged support (silica, diol and amide), cationic phase (triazole) and zwitterionic phase (sulfobetaine), that are commercially available were studied for the separation of a group of 12 polar pteridines. The main factors influencing the retention and selectivity of pteridines for these different HILIC systems have been studied in liquid chromatography-tandem mass spectrometry (LC-MS/MS) conditions: mobile phase composition, buffer type, pH and concentration and the separation mechanism was also investigated. Results of the effects of organic modifier, buffer pH and ion strength indicate that the retention mechanism is a mixed-mode of adsorption and ion exchange, and optimization of HILIC analyses depends on the ionization state of the analytes. For silica, diol, amide and sulfobetaine phases, hydrophilic partitioning mainly contributes to the retention, while electrostatic interactions and hydrogen-bonding should be considered to understand the elution orders for triazole phase. An zwitterionic phase (ZIC-HILIC) provided the stronger retention for all pteridines than other tested columns. PMID- 26838436 TI - Bull serum albumin coated Au@Agnanorods as SERS probes for ultrasensitive osteosarcoma cell detection. AB - Surface-Enhanced Raman scattering (SERS) has been widely used for imaging and sensing. However, limited reports are currently available on SERS-based cancer cell targeting strategy due to the challenge of synthesizing highly sensitive, reproducible and biocompatible SERS probe. Herein, we developed novel SERS probes, based on BSA (Bull Serum Albumin) coated gold-silver core-shell nanorods modified with Raman reporter 5,5-dithiobis 2-nitrobenzoic acid (DTNB) (Au@AgNRs@BSA@Anti-MICA), for in vitro cancer cell detection. Our results demonstrate that the SERS probe is very robust for cancer cell ultrasensitive detection with good biocompatibility and strong SERS signal. PMID- 26838437 TI - Fit-for-purpose chromatographic method for the determination of amikacin in human plasma for the dosage control of patients. AB - In this paper, a simple, rapid and sensitive method based on liquid chromatography with fluorimetric detection (HPLC-FLD) for the determination of amikacin (AMK) in human plasma is developed. Determination is performed by pre column derivatization of AMK with ortho-phtalaldehyde (OPA) in presence of N acetyl-L-cysteine (NAC) at pH 9.5 for 5 min at 80 degrees C. In our knowledge, this is the first time that NAC has been used in AMK derivatization. Derivatization conditions (pH, AMK/OPA/NAC molar ratios, temperature and reaction time) are optimized to obtain a single and stable, at room temperature, derivative. Separation of the derivative is achieved on a reversed phase LC column (Kromasil C18, 5 MUm, 150 * 4.6 i.d. mm) with a mobile phase of 0.05 M phosphate buffer:acetonitrile (80:20, v/v) pumped at flow rate of 1.0 mL/min. Detection is performed using 337 and 439 nm for excitation and emission wavelengths, respectively. The method is fitted for the purpose of being a competitive alternative to the currently used method in many hospitals for AMK dosage control: fluorescence polarization immunoassay (FPIA). The method exhibits linearity in the 0.17-10 ug mL(-1) concentration range with a squared correlation coefficient higher than 0.995. Trueness and intermediate precision are estimated using spiked drug free plasma samples, which fulfill current UNE-EN ISO15189:2007 accreditation schemes. Finally, for the first time, statistical comparison against the FPIA method is demonstrated using plasma samples from 31 patients under treatment with AMK. PMID- 26838438 TI - Development of traceable precision dynamic dilution method to generate dimethyl sulphide gas mixtures at sub-nanomole per mole levels for ambient measurement. AB - Dimethyl sulphide (DMS) is an important compound in global atmospheric chemistry and climate change. Traceable international standards are essential for measuring accurately the long-term global trend in ambient DMS. However, developing accurate gas standards for sub-nanomole per mole (nmol/mol) mole fractions of DMS in a cylinder is challenging, because DMS is reactive and unstable. In this study, a dynamic dilution method that is traceable and precise was developed to generate sub-nmol/mol DMS gas mixtures with a dynamic dilution system based on sonic nozzles and a long-term (>5 years) stable 10 MUmol/mol parent DMS primary standard gas mixtures (PSMs). The dynamic dilution system was calibrated with traceable methane PSMs, and its estimated dilution factors were used to calculate the mole fractions of the dynamically generated DMS gas mixtures. A dynamically generated DMS gas mixture and a 6 nmol/mol DMS PSM were analysed against each other by gas chromatography with flame-ionisation detection (GC/FID) to evaluate the dilution system. The mole fractions of the dynamically generated DMS gas mixture determined against a DMS PSM and calculated with the dilution factor agreed within 1% at 6 nmol/mol. In addition, the dynamically generated DMS gas mixtures at various mole fractions between 0.4 and 11.7 nmol/mol were analysed by GC/FID and evaluated for their linearity. The analytically determined mole fractions showed good linearity with the mole fractions calculated with the dilution factors. Results showed that the dynamic dilution method generates DMS gas mixtures ranging between 0.4 nmol/mol and 12 nmol/mol with relative expanded uncertainties of less than 2%. Therefore, the newly developed dynamic dilution method is a promising reference method for generating sub-nmol/mol DMS gas standards for accurate ambient measurements. PMID- 26838439 TI - Sample preparation for an optimized extraction of localized metabolites in lichens: Application to Pseudevernia furfuracea. AB - Lichens are symbiotic organisms known for producing unique secondary metabolites with attractive cosmetic and pharmacological properties. In this paper, we investigated three standard methods of preparation of Pseudevernia furfuracea (blender grinding, ball milling, pestle and mortar). The materials obtained were characterized by electronic microscopy, nitrogen adsorption and compared from the point of view of extraction. Their microscopic structure is related to extraction efficiency. In addition, it is shown using thalline reactions and mass spectrometry mapping (TOF-SIMS) that these metabolites are not evenly distributed throughout the organism. Particularly, atranorin (a secondary metabolite of interest) is mainly present in the cortex of P. furfuracea. Finally, using microwave assisted extraction (MAE) we obtained evidence that an appropriate preparation can increase the extraction efficiency of atranorin by a factor of five. PMID- 26838440 TI - Study on sensing strategy and performance of a microfluidic chemiluminescence aptazyme sensor. AB - Aptamers are analogous to antibodies in their range of target recognition. G quadruplex DNAzymes exhibit peroxidase-like activity toward certain specific reactions. Despite aptazyme sensors, based on aptamer and DNAzyme conjugates, have the potential to replace many conventional immune-biosensors; the mechanism concerning high background interference has scarcely been discussed. In this work, by taking a couple of aptazyme sensors with oligonucleotide sequences of adenosine aptamer and CatG4 DNAzyme, the sensing strategy dealing with the thermodynamic equilibrium of the functional oligonucleotide distribution had been studied. Oligonucleotide arrangement and cation condition were found important in modulating the shifting between Watson-Crick duplex and Hoogsteen G-quadruplex, which ultimately influenced sample and background signals. Notably, benefit from the microfluidic chemiluminescence detection, the developed aptazyme sensor achieved an absolute detection limit of 12 pmol adenosine with just 2 MUL of pretreated sample solution consumption and satisfactory selectivity. The results have implication for better design of aptazyme sensor in the future. PMID- 26838441 TI - Speciation of inorganic antimony (III & V) employing polyurethane foam loaded with bromopyrogallol red. AB - In this work, the speciation analysis of inorganic antimony (Sb(III) and Sb(V)) is proposed using polyurethane foam loaded with bromopyrogallol red (PUF-BPR) as a selective sorbent for Sb(III). The quantification of Sb in the solutions was performed by graphite furnace atomic absorption spectrometry (GF AAS), and several variables that could affect the performance of the method were carefully evaluated. The best conditions for the sorption of Sb(III) were achieved by shaking 50mg of PUF-BPR with the solutions containing Sb(III) at pH 4.0 for 90 min. In this condition, the retention of Sb(V) was not significant, whereas the removal of Sb(III) from the solution was higher than 95%. The desorption of Sb(III) from loaded PUF-BPR was possible by shaking the loaded foam with 7.5 mL of a 2.5 mol L(-1) HNO3 solution for 30 min. No interference of metal cations was observed on the solid-phase extraction of Sb(III) by PUF-BPR. The developed method was applied in the speciation analysis of antimony in river water samples fortified with different concentrations of Sb(III) and Sb(V). Also, we performed the determination of Sb(III) in a sample of a Sb-based drug utilized in the treatment of leishmaniasis. The results show that Sb(III) can be separated from high concentrations of Sb(V), since recoveries in the range of 81-110% were obtained in the analysis of the samples. The method presented limits of detection and quantification of 0.6 and 2 ug L(-1), respectively, for Sb(III) and 1 and 3 ug L(-1) for Sb(V), respectively. PMID- 26838442 TI - Stability and effectiveness of linear polyacrylamide capillary coating to suppress EOF in acidic media in the presence of surfactants, ionic liquids and organic modifiers. AB - Because of its high hydrophilicity, linear polyacrylamide (LPA) has often been used as a coating to suppress electroosmotic flow (EOF) in capillary electrophoresis (CE); however, its stability and effectiveness in acidic media, with or without organic modifiers, surfactants or ionic liquids is not well documented. In this work, the adequacy of LPA coating to suppress EOF in those different conditions was studied. It was shown that electroosmotic mobilities (uEO) did not change for at least 70h of non-stopped operation in all the tested conditions and the coating was stable. It was also shown that LPA coating efficiently suppresses EOF in acidic media (pH 4.0, 3.1, and 2.3) with or without organic modifiers (50% methanol or acetonitrile, ACN), as measured uEO values were between 18 and 84 times lower than those obtained with bare fused-silica capillaries. In acidic media with anionic surfactant (50mM sodium dodecylsulfate, SDS), ionic liquid (25 mM dodecyldimethylimidazolium bromide) or both SDS and ACN (buffer pH 2.1/ACN (8:2, v/v)+50mM SDS) EOF was reduced to a magnitude lower than with bare fused-silica capillaries, even though slight adsorptions of these surfactants were observed. LPA showed its superiority to hydroxypropyl cellulose, for which marked adsorption occurred because of its lower hydrophilicity. PMID- 26838443 TI - Evaluation of trace analyte identification in complex matrices by low-resolution gas chromatography--Mass spectrometry through signal simulation. AB - The identification of trace levels of compounds in complex matrices by conventional low-resolution gas chromatography hyphenated with mass spectrometry is based in the comparison of retention times and abundance ratios of characteristic mass spectrum fragments of analyte peaks from calibrators with sample peaks. Statistically sound criteria for the comparison of these parameters were developed based on the normal distribution of retention times and the simulation of possible non-normal distribution of correlated abundances ratios. The confidence level used to set the statistical maximum and minimum limits of parameters defines the true positive rates of identifications. The false positive rate of identification was estimated from worst-case signal noise models. The estimated true and false positive identifications rate from one retention time and two correlated ratios of three fragments abundances were combined using simple Bayes' statistics to estimate the probability of compound identification being correct designated examination uncertainty. Models of the variation of examination uncertainty with analyte quantity allowed the estimation of the Limit of Examination as the lowest quantity that produced "Extremely strong" evidences of compound presence. User friendly MS-Excel files are made available to allow the easy application of developed approach in routine and research laboratories. The developed approach was successfully applied to the identification of chlorpyrifos-methyl and malathion in QuEChERS method extracts of vegetables with high water content for which the estimated Limit of Examination is 0.14 mg kg(-1) and 0.23 mg kg(-1) respectively. PMID- 26838444 TI - Determination of selected synthetic cannabinoids and their metabolites by micellar electrokinetic chromatography--mass spectrometry employing perfluoroheptanoic acid-based micellar phase. AB - Perfluoroheptanoic acid was employed as a volatile micellar phase in background electrolyte for micellar electrokinetic chromatography-tandem mass spectrometry separation and determination of 15 selected naphthoyl- and phenylacetylindole- synthetic cannabinoids and main metabolites derived from JWH-018, JWH-019, JWH 073, JWH-200 and JWH-250. The influence of concentration of perfluoroheptanoic acid in background electrolytes on the separation was studied as well as the influence of perfluoroheptanoic acid on mass spectrometry detection. The background electrolyte consisted of 75 mM perfluoroheptanoic acid, 150 mM ammonium hydroxide pH 9.2 with 10% (v/v) propane-2-ol allowed micellar electrokinetic chromatography separation together with mass spectrometry identification of the studied parent synthetic cannabinoids and their metabolites. The limits of detection of studied synthetic cannabinoids and metabolites were in the range from 0.9 ng/mL for JWH-073 to 3.0 ng/mL for JWH-200 employing liquid-liquid extraction. The developed method was applied on the separation and identification of studied analytes after liquid-liquid extraction of spiked urine and serum samples to demonstrate the potential of the method applicability for forensic and toxicological purposes. PMID- 26838445 TI - A green ultrasonic-assisted liquid-liquid microextraction based on deep eutectic solvent for the HPLC-UV determination of ferulic, caffeic and cinnamic acid from olive, almond, sesame and cinnamon oil. AB - A simple, inexpensive and sensitive ultrasonic-assisted liquid-liquid microextraction method based on deep eutectic solvent (UALLME-DES) was used for the extraction of three phenolic acids (ferulic, caffeic and cinnamic) from vegetable oils. In a typical experiment, deep eutectic solvent as green extraction solvent was added to n-hexane (as a typical oil medium) containing target analytes. Subsequently, the extraction was accelerated by sonication. After the extraction, phase separation (DES rich phase/n-hexane phase) was performed by centrifugation. DES rich phase (lower phase) was withdrawn by a micro-syringe and submitted to isocratic reverse-phase HPLC with UV detection. Under optimum conditions obtained by response surface methodology (RSM) and desirability function (DF), the method has good linear calibration ranges (between 1.30 and 1000 ug L(-1)), coefficients of determination (r(2)>0.9949) and low limits of detection (between 0.39 and 0.63 ug L(-1)). This procedure was successfully applied to the determination of target analytes in olive, almond, sesame and cinnamon oil samples. The relative mean recoveries ranged from 94.7% to 104.6%. PMID- 26838446 TI - LC-MS/MS method development and validation for quantitative analyses of 2 aminothiazoline-4-carboxylic acid--a new cyanide exposure marker in post mortem blood. AB - 2-aminothiazoline-4-carboxylic acid (ATCA) is a hydrogen cyanide metabolite that has been found to be a reliable biomarker of cyanide poisoning, because of its long-term stability in biological material. There are several methods of ATCA determination; however, they are restricted to extraction on mixed mode cation exchange sorbents. To date, there has been no reliable method of ATCA determination in whole blood, the most frequently used material in forensic analysis. This novel method for ATCA determination in post mortem specimen includes protein precipitation, and derivatization of interfering compounds and their later extraction with ethyl acetate. ATCA was quantitatively analyzed via high performance liquid chromatography-tandem mass spectrometry with positive electrospray ionization detection using a hydrophilic interaction liquid chromatography column. The method satisfied all validation criteria and was tested on the real samples with satisfactory results. Therefore, this analytical approach has been proven to be a tool for measuring endogenous levels of ATCA in post mortem specimens. To conclude, a novel, accurate and sensitive method of ATCA determination in post mortem blood was developed. The establishment of the method provides new possibilities in the field of forensic science. PMID- 26838447 TI - Development and validation of a LC-MS/MS method for quantitative analysis of uraemic toxins p-cresol sulphate and indoxyl sulphate in saliva. AB - p-Cresol sulphate (pCS) and indoxyl sulphate (IS) are uraemic toxins, the concentration of which in serum correlate with the stage of renal failure. The aim of this study was to develop and validate a high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the analysis of pCS and IS in saliva. This is the first time, to our knowledge, that such a method has been developed using saliva. Unstimulated, fasting saliva was collected from healthy volunteers in the morning and pooled for validation assay. The method was validated for linearity, precision, accuracy, stability (freeze/thaw stability, stability in autosampler, short- and long-term stability, stock solution stability), dilution integrity and matrix effect. The analysed validation criteria were fulfilled. No influence of salivary flow (pCS: p=0.678; IS: p=0.238) nor type of swab in the Salivette device was detected. Finally, using the novel validated method, the saliva samples of healthy people (n=70) of various ages were analysed. We observed a tendency for an increase of concentration of toxins in saliva in the elderly. This could be a result of age related diseases, e.g., diabetes and kidney function decline. We can conclude that the novel LC-MS/MS method can be used for the determination of pCS and IS in human saliva. The results encourage the validation of saliva as a clinical sample for monitoring toxin levels in organisms. PMID- 26838448 TI - Programmable flow system for automation of oxygen radical absorbance capacity assay using pyrogallol red for estimation of antioxidant reactivity. AB - An automated oxygen radical absorbance capacity (ORAC) method based on programmable flow injection analysis was developed for the assessment of antioxidant reactivity. The method relies on real time spectrophotometric monitoring (540 nm) of pyrogallol red (PGR) bleaching mediated by peroxyl radicals in the presence of antioxidant compounds within the first minute of reaction, providing information about their initial reactivity against this type of radicals. The ORAC-PGR assay under programmable flow format affords a strict control of reaction conditions namely reagent mixing, temperature and reaction timing, which are critical parameters for in situ generation of peroxyl radical from 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). The influence of reagent concentrations and programmable flow conditions on reaction development was studied, with application of 37.5 uM of PGR and 125 mM of AAPH in the flow cell, guaranteeing first order kinetics towards peroxyl radicals and pseudo-zero order towards PGR. Peroxyl-scavenging reactivity of antioxidants, bioactive compounds and phenolic-rich beverages was estimated employing the proposed methodology. Recovery assays using synthetic saliva provided values of 90 +/- 5% for reduced glutathione. Detection limit calculated using the standard antioxidant compound Trolox was 8 MUM. RSD values were <3.4 and <4.9%, for intra and inter-assay precision, respectively. Compared to previous batch automated ORAC assays, the developed system also accounted for high sampling frequency (29 h(-1)), low operating costs and low generation of waste. PMID- 26838449 TI - Fabrication of surface plasmon resonance nanosensor for the selective determination of erythromycin via molecular imprinted nanoparticles. AB - The main objective of this study was to develop a novel surface plasmon resonance (SPR) nanosensor method based on a more rapid and selective determination of erythromycin (ERY) in the aqueous solution. This study is a combination of three techniques, which are miniemulsion polymerization, molecular imprinting and surface plasmon resonance techniques. In the first part, nanoparticles prepared with methacryl groups of functional monomer at surface acted as reactive sites for erythromycin as a template molecule. The molecularly imprinted nanoparticles were characterized by FTIR, SEM and zetasizer. After immobilization of nanoparticles on gold surface of SPR chip, nanosensor was characterized with contact angle measurements. This nanosensor was then used for selective determination of erythromycin. The linearity range and detection limit were obtained as 0.99 (r(2)) and 0.29 ppm, respectively. Association kinetic analysis, Scatchard, Langmuir, Freundlich and Freundlich-Langmuir isotherms were applied data. The selectivity of the SPR nanosensor was determined by using competitor agents (kanamycin sulfate, neomycin sulfate, spiramycin). The non-imprinted nanosensor was also used to evaluate the selectivity of ERY imprinted nanosensor. Finally, the nanosensor was tested for repeatability and it gave satisfactory response. These results demonstrate a method which is of low cost, rapid and provide reliable results in order to be used in detection of erythromycin from aqueous solution. PMID- 26838450 TI - "Molecular beacon"-hosted thioflavin T: Applications for label-free fluorescent detection of iodide and logic operations. AB - In this work, we presented a simple, label-free and rapid-responsive fluorescence assay for iodide (I(-)) detection based on "molecular beacon (MB)"-hosted thioflavin T (ThT), achieving a limit of detection as low as 158 nM. The proposed method exhibited very good selectivity to I(-) ions over other anions interference due to the strong binding force between I(-) ions with Hg(2+). Upon the addition of I(-) ions, it would capture Hg(2+) from a T-Hg(2+)-T complex belonging to the MB-like DNA hairpin structure, which eventually quenched the initial fluorescence as output. In addition, it was successfully applied for operation of an integrated DNA logic gate system and to the determination of I(-) in real samples such as human urine. PMID- 26838451 TI - A wearable fingernail chemical sensing platform: pH sensing at your fingertips. AB - This article demonstrates an example of a wearable chemical sensor based on a fingernail platform. Fingernails represent an attractive wearable platform, merging beauty products with chemical sensing, to enable monitoring of our surrounding environment. The new colorimetric pH fingernail sensor relies on coating artificial nails with a recognition layer consisted of pH indicators entrapped in a polyvinyl chloride (PVC) matrix. Such color changing fingernails offer fast and reversible response to pH changes, repeated use, and intense color change detected easily with naked eye. The PVC matrix prevents leaching out of the indicator molecules from the fingernail sensor toward such repeated use. The limited narrow working pH range of a single pH indicator has been addressed by multiplexing three different pH indicators: bromothymol blue (pH 6.0-7.6), bromocresol green (pH 3.8-5.4), and cresol red (pH 7.2-8.8), as demonstrated for analyses of real-life samples of acidic, neutral, and basic character. The new concept of an optical wearable chemical sensor on fingernail platforms can be expanded towards diverse analytes for various applications in connection to the judicious design of the recognition layer. PMID- 26838452 TI - Review of lignocellulolytic enzyme activity analyses and scale-down to microplate based assays. AB - With the increasing use of enzymes in environmental applications, there is a need for analytical methods adapted to large factorial experiments. Existing reference methods are chemical and labor intensive and unsuitable to analyze in parallel a large number of samples. Based on an extensive literature review and on experimental results, this work compares reference and microplate adapted methods to define the most adequate filter paper, carboxymethylcellulase, beta glucosidase and xylanase activity tests. In the adapted methods, the total reaction volume was reduced from 2.2-24.5 mL to 0.21-0.24 mL. Statistical analysis of the activities measured on enzyme mixtures by applying the 96-well plate reduced methods showed that they were not significantly different to the activities obtained with reference tests. PMID- 26838453 TI - A methodological approach based on gold-nanoparticles followed by matrix assisted laser desorption ionization time of flight mass spectrometry for the analysis of urine profiling of knee osteoarthritis. AB - The aim of this work is to develop a nanoparticle-based methodology to find out biomarkers of diagnostic for knee osteoarthritis, KOA, through the use of matrix assisted laser desorption ionization time-of-flight-based mass spectrometry profiling. Urine samples used for this study were obtained from KOA patients (42 patients), patients with prosthesis (58 patients), and controls (36 individuals) with no history of joint disease. Gold-nano particle MALDI-based urine profiling was optimized and then applied over the 136 individuals. Jaccard index and 10 different classifiers over MALDI MS datasets were used to find out potential biomarkers. Then, the specificity and sensitivity of the method were evaluated. The presence of ten m/z signals as potential biomarkers in the healthy versus non healthy approach suggests that patients (KOA and prosthesis) are differentiable from the healthy volunteers through profiling. The automatic diagnostic study confirmed these preliminary conclusions. The sensitivity and the specificity for the urine profiling criteria here reported, achieved by the C4.5 classifier, is 97% and 69% respectively. Thus, it is confirmed the utility of the method proposed in this work as an additional fast, non-expensive and robust test for KOA diagnostic. When the proposed method is compared with those used in common practice it is found that sensitivity is the highest, thus with a low false negative rate for diagnostic KOA patients in the population studied. Specificity is lower but in the range accepted for diagnostic objectives. PMID- 26838454 TI - A highly sensitive and stable glucose biosensor using thymine-based polycations into laponite hydrogel films. AB - A series of glucose bioelectrodes were prepared by glucose oxidase (GOx) immobilization into laponite hydrogel films containing DNA bioinspired polycations made of vinylbenzyl thymine (VBT) and vinylbenzyl triethylammonium chloride (VBA) with general formulae (VBT)m(VBA)n](n+)~25 with m=0, 1 and n=2, 4, 8, deposited onto glassy carbon electrode. The bioelectrodes were characterized by chronoamperometry, cyclic voltammetry and electrochemical impedance spectroscopy. Results indicated that the electrochemical properties of the laponite hydrogel films were largely improved by the incorporation of thymine based polycations, being proportional to the positive charge density of the polycation molecule. After incorporation of glucose oxidase, the sensitivity of the bioelectrode to glucose increased with the positive charge density of the polycation. Additionally, the presence of the vinylbenzyl thymine moiety played a role in the long-term stability and reproducibility of the bioelectrode signal. As a consequence, the [(VBT)(VBA)8](8+)~25 was the most appropriate polycation for bioelectrode preparation and glucose sensing, with a specific sensitivity of se=176 mA mmol(-1)Lcm(-2)U(-1), almost two-order of magnitude larger than other laponite immobilized GOx bioelectrodes reported elsewhere. These features were confirmed by testing the bioelectrode for a selective determination of glucose in powder milk and blood serum samples without interference of either ascorbic or uric acids under the experimental conditions. The present study demonstrates the suitability of DNA bioinspired water-soluble polycations [(VBT)m(VBA)n](n+)~25 for enzyme immobilization like GOx into laponite hydrogels, and the preparation of highly sensitive and stable bioelectrodes on glassy carbon surface. PMID- 26838455 TI - Stepwise injection potentiometric determination of caffeine in saliva using single-drop microextraction combined with solvent exchange. AB - A flow potentiometric method for determination of caffeine in saliva is suggested. This task is important for non-invasive assessment of drug metabolizing system activity in hepatocytes. In the current study, stepwise injection analysis (SWIA) was successfully combined with single-drop liquid microextraction (SDLME) and solvent exchange procedure. The method is based on the caffeine SDLME with subsequent solvent evaporation and dissolution of analyte in sulfuric acid followed by potentiometric detection using poly(vinyl chloride) membrane electrode containing potassium tetrakis[3,5 bis(trifluoromethyl)phenyl]borate as electroactive component. SDLME was employed for elimination of interfering matrix effects of saliva and caffeine metabolites such as theophylline, theobromine and paraxanthine. A linear range of 10(-5)-10( 2)M was established for caffeine with detection limit at 6 * 10(-6)M. The sample throughput was 6 samples h(-1). The proposed method was successfully applied to the determination of caffeine in saliva and the analytical results agreed well with the results obtained with reference HPLC method. PMID- 26838456 TI - Dendritic DNA-porphyrin as mimetic enzyme for amplified fluorescent detection of DNA. AB - In this work, a novel dendritic DNA-porphyrin superstructure was designed as mimetic enzyme for the amplified fluorescent detection of DNA. The dendritic DNA superstructure was in situ assembled with three auxiliary DNAs via hybridization chain reaction. With groove interaction between iron porphyrin (FeTMPyP) and double-stranded DNA, the dendritic DNA superstructure is capable to gather abundant FeTMPyP molecules to form dendritic DNA-FeTMPyP mimetic enzyme. Using tyramine as a substrate, the dendritic DNA-FeTMPyP demonstrated excellent peroxidase-like catalytic oxidation of tyramine into fluorescent dityramine in the presence of H2O2. Based on an amplified fluorescence signal, a signal on strategy is proposed for DNA detection with high sensitivity, good specificity and practicability. The assembly of porphyrin with dendritic DNA not only provided the new avenue to construct mimetic enzyme but also established label free sensing platform for a wide range of analytes. PMID- 26838457 TI - Enhanced chemiluminescence detection of glutathione based on isoluminol-PSM nanoparticles probe. AB - In this paper, a new chemiluminescence (CL) strategy was constructed for the determination of physiological thiols by using an isoluminol labeled nano-probe. The amino group on the surface of the magnetic beads (MBs) were converted into pyridyl disulfide groups by treatment with N-succinimidyl-3-(2 pyridyldithio)propionate (SPDP), in the meantime, isoluminol and thiolated signal DNA were labeled on the surface of the polystyrene microspheres (PSMs). By treating the SPDP activated MBs with the modified PSMs, isoluminol molecules on the surface of the PSMs, along with the thiolated signal DNA, were attached to the surface of the MBs through disulfide bonds to form a CL probe. In the presence of glutathione (GSH), the disulfide bonds could be cleaved readily. The isoluminol molecules modified on the surface of the PSMs released from the CL probes were detached by magnetic separation and transferred to the dark closet for CL detection of isoluminol-H2O2-HRP system. Using GSH detection as a model, we prove a linear dose response in the range from 5 * 10(-10) to 8 * 10(-8)M. The detection limit of this trial for GSH determined is 5 * 10(-10)M. The proposed design was successfully applied to the extracts of K562 cell for intracellular thiols detection, the average amount of thiols was about 4.114 * 10(-13)M per K562 cell. PMID- 26838458 TI - Aptamer based peptide enrichment for quantitative analysis of gonadotropin releasing hormone by LC-MS/MS. AB - Over recent years threats to racing have expanded to include naturally occurring biological molecules, such as peptides and proteins, and their synthetic analogues. Traditionally, antibodies have been used to enable detection of these compounds as they allow purification and concentration of the analyte of interest. The rapid expansion of peptide-based therapeutics necessitates a similarly rapid development of suitable antibodies or other means of enrichment. Potential alternative enrichment strategies include the use of aptamers, which offer the significant advantage of chemical synthesis once the nucleic acid sequence is known. A method was developed for the enrichment, detection and quantitation of gonadotropin-releasing hormone (GnRH) in equine urine using aptamer-based enrichment and LC-MS/MS. The method achieved comparable limits of detection (1 pg/mL) and quantification (2.5 pg/mL) to previously published antibody-based enrichment methods. The intra- and inter-assay precision achieved was less than 10% at both 5 and 20 pg/mL, and displayed a working dynamic range of 2.5-100 pg/mL. Significant matrix enhancement (170 +/- 8%) and low analytical recovery (29 +/- 15%) was observed, although the use of an isotopically heavy labelled GnRH peptide, GnRH (Pro(13)C5,(15)N), as the internal standard provides compensation for these parameters. Within the current limits of detection GnRH was detectable up to 1h post administration in urine and identification of a urinary catabolite extended this detection window to 4h. Based on the results of this preliminary investigation we propose the use of aptamers as a viable alternative to antibodies in the enrichment of peptide targets from equine urine. PMID- 26838460 TI - Evaluation of Perrhenate Spectrophotometric Methods in Bicarbonate and Nitrate Media. AB - 2-pyridyl thiourea and methyl-2-pyridyl ketoxime based perrhenate, Re(VII), UV vis spectrophotometric methods were evaluated in nitrate and bicarbonate solutions ranging from 0.001 M to 0.5 M. Standard curves at [Re]=2.5-50 mg L(-1) for the Re(IV)-thiourea and the Re ketoxime complexes were constructed at 405 nm and 490 nm, respectively. Detection of limits for N-(2-pyridyl) thiourea and methyl-2-pyridyl ketoxime methods in ultrapure water are 3.06 mg/L and 4.03 mg/L, respectively. Influences of NaHCO3 and NaNO3 concentration on absorbance spectra, absorptivity, and linearity were documented. For both methods, samples in ultrapure water and NaHCO3 have an R(2) value>0.99, indicating strong linear relationships. Statistical analysis supports that NaHCO3 does not affect linearity between standards for either method. NaNO3 causes major interference with the ketoxime method above 0.001 M NaNO3. Data provides information for practical use of Re spectrophotometric methods in environmental media that is high in bicarbonate and nitrate. PMID- 26838459 TI - Influence of the collection tube on metabolomic changes in serum and plasma. AB - Major threats in metabolomics clinical research are biases in sampling and preparation of biological samples. Bias in sample collection is a frequently forgotten aspect responsible for uncontrolled errors in metabolomics analysis. There is a great diversity of blood collection tubes for sampling serum or plasma, which are widely used in metabolomics analysis. Most of the existing studies dealing with the influence of blood collection on metabolomics analysis have been restricted to comparison between plasma and serum. However, polymeric gel tubes, which are frequently proposed to accelerate the separation of serum and plasma, have not been studied. In the present research, samples of serum or plasma collected in polymeric gel tubes were compared with those taken in conventional tubes from a metabolomics perspective using an untargeted GC-TOF/MS approach. The main differences between serum and plasma collected in conventional tubes affected to critical pathways such as the citric acid cycle, metabolism of amino acids, fructose and mannose metabolism and that of glycerolipids, and pentose and glucuronate interconversion. On the other hand, the polymeric gel only promoted differences at the metabolite level in serum since no critical differences were observed between plasma collected with EDTA tubes and polymeric gel tubes. Thus, the main changes were attributable to serum collected in gel and affected to the metabolism of amino acids such as alanine, proline and threonine, the glycerolipids metabolism, and two primary metabolites such as aconitic acid and lactic acid. Therefore, these metabolite changes should be taken into account in planning an experimental protocol for metabolomics analysis. PMID- 26838461 TI - Smart detection of microRNAs through fluorescence enhancement on a photonic crystal. AB - The detection of low abundant biomarkers, such as circulating microRNAs, demands innovative detection methods with increased resolution, sensitivity and specificity. Here, a biofunctional surface was implemented for the selective capture of microRNAs, which were detected through fluorescence enhancement directly on a photonic crystal. To set up the optimal biofunctional surface, epoxy-coated commercially available microscope slides were spotted with specific anti-microRNA probes. The optimal concentration of probe as well as of passivating agent were selected and employed for titrating the microRNA hybridization. Cross-hybridization of different microRNAs was also tested, resulting negligible. Once optimized, the protocol was adapted to the photonic crystal surface, where fluorescent synthetic miR-16 was hybridized and imaged with a dedicated equipment. The photonic crystal consists of a dielectric multilayer patterned with a grating structure. In this way, it is possible to take advantage from both a resonant excitation of fluorophores and an angularly redirection of the emitted radiation. As a result, a significant fluorescence enhancement due to the resonant structure is collected from the patterned photonic crystal with respect to the outer non-structured surface. The dedicated read-out system is compact and based on a wide-field imaging detection, with little or no optical alignment issues, which makes this approach particularly interesting for further development such as for example in microarray-type bioassays. PMID- 26838462 TI - Evidence for the stability of the West Antarctic Ice Sheet divide for 1.4 million years. AB - Past fluctuations of the West Antarctic Ice Sheet (WAIS) are of fundamental interest because of the possibility of WAIS collapse in the future and a consequent rise in global sea level. However, the configuration and stability of the ice sheet during past interglacial periods remains uncertain. Here we present geomorphological evidence and multiple cosmogenic nuclide data from the southern Ellsworth Mountains to suggest that the divide of the WAIS has fluctuated only modestly in location and thickness for at least the last 1.4 million years. Fluctuations during glacial-interglacial cycles appear superimposed on a long term trajectory of ice-surface lowering relative to the mountains. This implies that as a minimum, a regional ice sheet centred on the Ellsworth-Whitmore uplands may have survived Pleistocene warm periods. If so, it constrains the WAIS contribution to global sea level rise during interglacials to about 3.3 m above present. PMID- 26838464 TI - Establishment of cell-based transposon-mediated transgenesis in cattle. AB - Transposon-mediated transgenesis is a well-established tool for genome modification in small animal models. However, translation of this active transgenic method to large animals warrants further investigations. Here, the piggyBac (PB) and sleeping beauty (SB) transposon systems were assessed for stable gene transfer into the cattle genome. Bovine fibroblasts were transfected either with a helper-independent PB system or a binary SB system. Both transposons were highly active in bovine cells increasing the efficiency of DNA integration up to 88 times over basal nonfacilitated integrations in a colony formation assay. SB transposase catalyzed multiplex transgene integrations in fibroblast cells transfected with the helper vector and two donor vectors carrying different transgenes (fluorophore and neomycin resistance). Stably transfected fibroblasts were used for SCNT and on in vitro embryo culture, morphologically normal blastocysts that expressed the fluorophore were obtained with both transposon systems. The data indicate that transposition is a feasible approach for genetic engineering in the cattle genome. PMID- 26838463 TI - Mathematical modelling of phenotypic plasticity and conversion to a stem-cell state under hypoxia. AB - Hypoxia, or oxygen deficiency, is known to be associated with breast tumour progression, resistance to conventional therapies and poor clinical prognosis. The epithelial-mesenchymal transition (EMT) is a process that confers invasive and migratory capabilities as well as stem cell properties to carcinoma cells thus promoting metastatic progression. In this work, we examined the impact of hypoxia on EMT-associated cancer stem cell (CSC) properties, by culturing transformed human mammary epithelial cells under normoxic and hypoxic conditions, and applying in silico mathematical modelling to simulate the impact of hypoxia on the acquisition of CSC attributes and the transitions between differentiated and stem-like states. Our results indicate that both the heterogeneity and the plasticity of the transformed cell population are enhanced by exposure to hypoxia, resulting in a shift towards a more stem-like population with increased EMT features. Our findings are further reinforced by gene expression analyses demonstrating the upregulation of EMT-related genes, as well as genes associated with therapy resistance, in hypoxic cells compared to normoxic counterparts. In conclusion, we demonstrate that mathematical modelling can be used to simulate the role of hypoxia as a key contributor to the plasticity and heterogeneity of transformed human mammary epithelial cells. PMID- 26838465 TI - Continuous presence of male on estrus onset, estrus duration, and ovulation in estrus-synchronized Boer goats. AB - The objectives of the present study were to assess the effect of permanent contact of teasers without copulation on the interval from controlled internal drug release (CIDR) removal to estrus onset, estrus duration, ovulation time, number of ovulations, and interval from CIDR removal to ovulation time on estrus synchronized Boer goats. During the fall season, a controlled randomized design experiment with two groups, control (CON; n = 18) and treatment (TRE; n = 18), was performed. The TRE group was maintained permanently in a pen with an aproned buck immediately after CIDR removal. The CON group was maintained in a different pen without permanent exposure to the male. All females were estrus synchronized with CIDR maintained in the vagina for 7 days and received 50 MUg of GnRH im at device insertion and 5 mg of natural prostaglandin F-2alpha at device removal. Females were considered to be in estrus when they accepted mounting by the aproned bucks. Estrus was detected four times a day after CIDR removal (at 6 AM, 12 noon, 6 PM, and 12 midnight) using bucks with canvas apron as teasers. The ovulation time and number of ovulations were assessed by transrectal ultrasonography starting 24 hours after estrus onset and repeated every 6 hours until complete ovulation was detected. The estrus onset for the CON group was 44.0 +/- 8.3 hours and for the TRE group, it was 37.0 +/- 7.7 hours (P = 0.01). Estrus duration from the CON group was 43.7 +/- 9.2 hours and for the TRE group, it was 38.3 +/- 6.6 hours (P = 0.05). The first, last, and mean ovulation times for the CON group were 32.4 +/- 5.3, 38.4 +/- 3.4, and 35.4 +/- 3.9 hours, and for the TRE group, the times were 31.8 +/- 2.8, 36.7 +/- 3.0, and 35.8 +/- 3.6 hours, respectively (P = 0.85, P = 0.23, and P = 0.82, respectively). The number of ovulations for the CON and TRE groups was 2.6 +/- 0.7 and 2.6 +/- 0.6 ovulations, respectively (P = 0.96). The interval time for CIDR removal to ovulation for the CON group was 79.2 +/- 8.2 hours and for the TRE group, the interval time was 73.2 +/- 6.2 hours (P = 0.05). It was concluded that the permanent presence of male without copulation with estrus-synchronized does hastened estrus onset, reduced estrus duration, and decreased the interval time from CIDR removal to ovulation without modification of ovulation time and number of ovulations in Boer goats. PMID- 26838466 TI - BDNF-induced expansion of cumulus-oocyte complexes in pigs was mediated by microRNA-205. AB - The neurotrophin family of proteins is required for the survival and differentiation of the nervous system and is important to the development of reproductive tissues. The objectives of the present study were to detect the presence of the brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor protein in cumulus-oocyte complexes in pigs and to explore the role of microRNAs in the BDNF-induced in vitro maturation of oocytes. We demonstrate that both BDNF and tyrosine kinase receptor protein are expressed in porcine cumulus oocyte complexes. BDNF supplementation promotes the in vitro maturation of porcine oocytes. MiRNA-205 is downregulated during the BDNF-induced maturation of oocytes. The overexpression of miRNA-205 in granulosa cells and reporter gene assay shows that the marker gene ptx3 for cumulus expansion is the putative target gene of miR-205. Our data provide evidence that the BDNF-induced maturation of oocytes in pigs may be mediated by miR-205 through the regulation of potential target gene, ptx3. PMID- 26838468 TI - It stops with us: Peer responses increase availability of sterile injecting equipment. PMID- 26838467 TI - Human behaviour can trigger large carnivore attacks in developed countries. AB - The media and scientific literature are increasingly reporting an escalation of large carnivore attacks on humans in North America and Europe. Although rare compared to human fatalities by other wildlife, the media often overplay large carnivore attacks on humans, causing increased fear and negative attitudes towards coexisting with and conserving these species. Although large carnivore populations are generally increasing in developed countries, increased numbers are not solely responsible for the observed rise in the number of attacks by large carnivores. Here we show that an increasing number of people are involved in outdoor activities and, when doing so, some people engage in risk-enhancing behaviour that can increase the probability of a risky encounter and a potential attack. About half of the well-documented reported attacks have involved risk enhancing human behaviours, the most common of which is leaving children unattended. Our study provides unique insight into the causes, and as a result the prevention, of large carnivore attacks on people. Prevention and information that can encourage appropriate human behaviour when sharing the landscape with large carnivores are of paramount importance to reduce both potentially fatal human-carnivore encounters and their consequences to large carnivores. PMID- 26838469 TI - Psychedelics and cognitive liberty: Reimagining drug policy through the prism of human rights. AB - This paper reimagines drug policy--specifically psychedelic drug policy--through the prism of human rights. Challenges to the incumbent prohibitionist paradigm that have been brought from this perspective to date--namely by calling for exemptions from criminalisation on therapeutic or religious grounds--are considered, before the assertion is made that there is a need to go beyond such reified constructs, calling for an end to psychedelic drug prohibitions on the basis of the more fundamental right to cognitive liberty. This central concept is explicated, asserted as being a crucial component of freedom of thought, as enshrined within Article 9 of the European Convention on Human Rights (ECHR). It is argued that the right to cognitive liberty is routinely breached by the existence of the system of drug prohibition in the United Kingdom (UK), as encoded within the Misuse of Drugs Act 1971 (MDA). On this basis, it is proposed that Article 9 could be wielded to challenge the prohibitive system in the courts. This legal argument is supported by a parallel and entwined argument grounded in the political philosophy of classical liberalism: namely, that the state should only deploy the criminal law where an individual's actions demonstrably run a high risk of causing harm to others. Beyond the courts, it is recommended that this liberal, rights-based approach also inform psychedelic drug policy activism, moving past the current predominant focus on harm reduction, towards a prioritization of benefit maximization. How this might translate in to a different regulatory model for psychedelic drugs, a third way, distinct from the traditional criminal and medical systems of control, is tentatively considered. However, given the dominant political climate in the UK--with its move away from rights and towards a more authoritarian drug policy--the possibility that it is only through underground movements that cognitive liberty will be assured in the foreseeable future is contemplated. PMID- 26838471 TI - Disaster response for people with disability. AB - Emergency Preparedness for people with a disability has been a steadfast activity in the state of South Carolina. In October 2015, the state experienced a natural disaster termed "The 1000 Year Flood". The disability response to the disaster was swift due to the strong collaborative network. However, the disaster did present challenges that need to be further addressed. The retelling of South Carolina's response should be informative to other state programs that provide advocacy for people with disability. Agencies and organizations that respond to disasters can learn from South Carolina's experience to ensure that the needs of people with disabilities are addressed rapidly and efficiently. PMID- 26838470 TI - An ethnographic exploration of drug markets in Kisumu, Kenya. AB - BACKGROUND: Illegal drug markets are shaped by multiple forces, including local actors and broader economic, political, social, and criminal justice systems that intertwine to impact health and social wellbeing. Ethnographic analyses that interrogate multiple dimensions of drug markets may offer both applied and theoretical insights into drug use, particularly in developing nations where new markets and local patterns of use traditionally have not been well understood. This paper explores the emergent drug market in Kisumu, western Kenya, where our research team recently documented evidence of injection drug use. METHODS: Our exploratory study of injection drug use was conducted in Kisumu from 2013 to 2014. We draw on 151 surveys, 29 in-depth interviews, and 8 months of ethnographic fieldwork to describe the drug market from the perspective of injectors, focusing on their perceptions of the market and reports of drug use therein. RESULTS: Injectors described a dynamic market in which the availability of drugs and proliferation of injection drug use have taken on growing importance in Kisumu. In addition to reports of white and brown forms of heroin and concerns about drug adulteration in the market, we unexpectedly documented widespread perceptions of cocaine availability and injection in Kisumu. Examining price data and socio-pharmacological experiences of cocaine injection left us with unconfirmed evidence of its existence, but opened further possibilities about how the chaos of new drug markets and diffusion of injection-related beliefs and practices may lend insight into the sociopolitical context of western Kenya. CONCLUSIONS: We suggest a need for expanded drug surveillance, education and programming responsive to local conditions, and further ethnographic inquiry into the social meanings of emergent drug markets in Kenya and across sub-Saharan Africa. PMID- 26838472 TI - You say you want a revolution: An empirical study of community-based participatory research with people with developmental disabilities. AB - BACKGROUND: Community-based participatory research (CBPR) seeks to improve the responsiveness of science to community priorities and foster positive community change through equitable research collaborations between scientists and community members. CBPR resonates with disability rights principles, and is increasingly being used in disability research, though there are few studies of its use with people with developmental disabilities. OBJECTIVE: We conducted a prospective qualitative study to explore the experiences of scientists and community members in a multi-year CBPR project with people with developmental disabilities. METHODS: Over the four project years, we conducted periodic individual interviews and focus groups with members of the CBPR project, and used an inductive thematic analysis to identify and develop relational themes. RESULTS: We identified factors that contributed to the success of the CBPR project and factors that presented challenges to the CBPR project. We also identified potential individual, project, and societal level impacts of the CBPR project. CONCLUSIONS: CBPR with people with developmental disabilities is possible and fruitful, and can serve as an effective model for the full inclusion of people with developmental disabilities in science and society at large. PMID- 26838473 TI - Formation of reactive aldehydes (MDA, HHE, HNE) during the digestion of cod liver oil: comparison of human and porcine in vitro digestion models. AB - In this work, we investigated lipid oxidation of cod liver oil during gastrointestinal (GI) digestion using two types of in vitro digestion models. In the first type of model, we used human GI juices, while we used digestive enzymes and bile from porcine origin in the second type of model. Human and porcine models were matched with respect to factors important for lipolysis, using a standardized digestion protocol. The digests were analysed for reactive oxidation products: malondialdehyde (MDA), 4-hydroxy-trans-2-nonenal (HNE), and 4-hydroxy trans-2-hexenal (HHE) by liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (LC/APCI-MS), and for free fatty acids (FFA) obtained during the digestion by gas chromatography-mass spectrometry (GC-MS). The formation of the oxidation products MDA, HHE, and HNE was low during the gastric digestion, however, it increased during the duodenal digestion. The formation of the oxidation products reached higher levels when digestive juices of human origin were used (60 MUM of MDA, 0.96 MUM of HHE, and 1.6 MUM of HNE) compared to when using enzymes and bile of porcine origin (9.8, and 0.36 MUM of MDA; 0.16, and 0.026 MUM of HHE; 0.23, and 0.005 MUM of HNE, respectively, in porcine models I and II). In all models, FFA release was only detected during the intestinal step, and reached up to 31% of total fatty acids (FA). The findings in this work may be of importance when designing oxidation oriented lipid digestion studies. PMID- 26838476 TI - Cooperative Extension: A Model of Science-Practice Integration for Ecosystem Restoration. AB - Restoration ecology is a science, driven by practical application. Despite the well-recognized disconnect between the science and practice of ecological restoration, there is a lack of practical solutions. In 2014, US agriculture marked the 100th anniversary of the Cooperative Extension Service, providing a timely reminder that the divide between science and practice can be bridged successfully. Major restoration efforts are underway across the globe and integrated science-practice communication is required to avoid project failure and a significant waste of resources. Here, we propose a three-tiered approach, re-emphasizing the integration of science-based practice in restoration utilizing the structure, function, and potential for success of the Cooperative Extension Service of the US Department of Agriculture (USDA) as a model for connecting science and practice in ecosystem restoration. PMID- 26838474 TI - Liver-derived ketone bodies are necessary for food anticipation. AB - The circadian system has endowed animals with the ability to anticipate recurring food availability at particular times of day. As daily food anticipation (FA) is independent of the suprachiasmatic nuclei, the central pacemaker of the circadian system, questions arise of where FA signals originate and what role components of the circadian clock might play. Here we show that liver-specific deletion of Per2 in mice abolishes FA, an effect that is rescued by viral overexpression of Per2 in the liver. RNA sequencing indicates that Per2 regulates beta-hydroxybutyrate (betaOHB) production to induce FA leading to the conclusion that liver Per2 is important for this process. Unexpectedly, we show that FA originates in the liver and not in the brain. However, manifestation of FA involves processing of the liver-derived betaOHB signal in the brain, indicating that the food-entrainable oscillator is not located in a single tissue but is of systemic nature. PMID- 26838475 TI - Role of brassinosteroid signaling in modulating Tobacco mosaic virus resistance in Nicotiana benthamiana. AB - Plant steroid hormones, brassinosteroids (BRs), play essential roles in plant growth, development and stress responses. However, mechanisms by which BRs interfere with plant resistance to virus remain largely unclear. In this study, we used pharmacological and genetic approaches in combination with infection experiments to investigate the role of BRs in plant defense against Tobacco Mosaic Virus (TMV) in Nicotiana benthamiana. Exogenous applied BRs enhanced plant resistance to virus infection, while application of Bikinin (inhibitor of glycogen synthase kinase-3), which activated BR signaling, increased virus susceptibility. Silencing of NbBRI1 and NbBSK1 blocked BR-induced TMV resistance, and silencing of NbBES1/BZR1 blocked Bikinin-reduced TMV resistance. Silencing of NbMEK2, NbSIPK and NbRBOHB all compromised BR-induced virus resistance and defense-associated genes expression. Furthermore, we found MEK2-SIPK cascade activated while BES1/BZR1 inhibited RBOHB-dependent ROS production, defense gene expression and virus resistance induced by BRs. Thus, our results revealed BR signaling had two opposite effects on viral defense response. On the one hand, BRs enhanced virus resistance through MEK2-SIPK cascade and RBOHB-dependent ROS burst. On the other hand, BES1/BZR1 inhibited RBOHB-dependent ROS production and acted as an important mediator of the trade-off between growth and immunity in BR signaling. PMID- 26838477 TI - A theranostic nrGO@MSN-ION nanocarrier developed to enhance the combination effect of sonodynamic therapy and ultrasound hyperthermia for treating tumor. AB - Sonodynamic therapy (SDT), which induces activation of sonosensitizers in cancer cells through ultrasound irradiation, has emerged as an alternative and promising noninvasive therapeutic approach to kill both superficial and deep parts of tumors. In this study, mesoporous silica (MSN) grown on reduced graphene oxide nanosheet (nrGO) capped with Rose Bengal (RB)-PEG-conjugated iron-oxide nanoparticles (IONs), nrGO@MSN-ION-PEG-RB, was strategically designed to have targeted functionality and therapeutic efficacy under magnetic guiding and focused ultrasound (FUS) irradiation, respectively. The singlet oxygen produced by ultrasound-activated RB and the ultrasound-induced heating effect was enhanced by rGO and IONs, which improved the cytotoxic effect in cancer cells. In an animal experiment, we demonstrated that the combination of sonodynamic/hyperthermia therapy with magnetic guidance using this nanocomposite therapeutic agent can produce remarkable efficacious therapy in tumor growth inhibition. Furthermore, the combination effect induced by FUS irradiation produces significant damage to both superficial and deep parts of the targeted tumor. PMID- 26838478 TI - Remembering Charles B. Huggins' Nobel Prize for Hormonal Treatment of Prostatic Cancer at its 50th Anniversary. AB - Charles B. Huggins received the Nobel Prize in 1966. Based on archival sources from the Nobel archive we have found that nominators emphasised the practical therapeutic applications of his discoveries that were showing 25 yr after his key publications. PMID- 26838479 TI - Re: Eduard Baco, Erik Rud, Lars Magne Eri, et al. A Randomized Controlled Trial to Assess and Compare the Outcomes of Two-core Prostate Biopsy Guided by Fused Magnetic Resonance and Transrectal Ultrasound Images and Traditional 12-core Systematic Biopsy. Eur Urol 2016;69:149-56. PMID- 26838480 TI - Simulated effect of calcification feedback on atmospheric CO2 and ocean acidification. AB - Ocean uptake of anthropogenic CO2 reduces pH and saturation state of calcium carbonate materials of seawater, which could reduce the calcification rate of some marine organisms, triggering a negative feedback on the growth of atmospheric CO2. We quantify the effect of this CO2-calcification feedback by conducting a series of Earth system model simulations that incorporate different parameterization schemes describing the dependence of calcification rate on saturation state of CaCO3. In a scenario with SRES A2 CO2 emission until 2100 and zero emission afterwards, by year 3500, in the simulation without CO2 calcification feedback, model projects an accumulated ocean CO2 uptake of 1462 PgC, atmospheric CO2 of 612 ppm, and surface pH of 7.9. Inclusion of CO2 calcification feedback increases ocean CO2 uptake by 9 to 285 PgC, reduces atmospheric CO2 by 4 to 70 ppm, and mitigates the reduction in surface pH by 0.003 to 0.06, depending on the form of parameterization scheme used. It is also found that the effect of CO2-calcification feedback on ocean carbon uptake is comparable and could be much larger than the effect from CO2-induced warming. Our results highlight the potentially important role CO2-calcification feedback plays in ocean carbon cycle and projections of future atmospheric CO2 concentrations. PMID- 26838481 TI - Ventilation/Perfusion SPECT lung scintigraphy and computed tomography pulmonary angiography in patients with clinical suspicion of pulmonary embolism. AB - The aim was to compare ventilation/perfusion SPECT lung scintigraphy (V/Q-SPECT) and computed tomography pulmonary angiography (CTPA) in patients with suspicion of pulmonary embolism (PE). MATERIAL AND METHODS: This prospectively designed study included 53 patients with intermediate or high clinical probability of PE. A V/Q-SPECT and CTPA was performed on all patients. The V/Q-SPECT was interpreted according to the European Association of Nuclear Medicine and Molecular Imaging (EANMMI) guidelines. CTPA was reported as positive, negative, or indeterminate. RESULTS: CTPA was positive in 22 cases, negative in 28, and indeterminate in 3. V/Q-SPECT was positive in 27 cases, negative in 24, and non-diagnostic in 2. In the 22 with positive CTPA, V/Q-SPECT was positive in 18, negative in 3, and non diagnostic in 1. In the 28 with negative CTPA, V/Q-SPECT was positive in 8, negative in 19, and non-diagnostic in 1. In the 3 with indeterminate CTPA, V/Q SPECT was positive in 1 and negative in 2. In the 2 non-diagnostic cases V/Q SPECT, CTPA was positive in 1 and negative in one. In the 10 high clinical probabilities, CTPA and V/Q-SPECT were positive in 7, negative in 2, and in 1, CTPA was positive and V/Q-SPECT negative. In the 38 intermediate probability group, CTPA and V/Q-SPECT were positive in 11, negative in 17, with CTPA negative and V/Q-SPECT positive in 8, and in 2 CTPA was positive and V/Q-SPECT negative. The results show that V/Q-SPECT detected PE in 5 patients more than CTPA. CONCLUSION: Our results show a 77% concordance of both techniques. Overall V/Q SPECT detected PE in 18% more patients than CTPA in the intermediate group. Both techniques have a complementary role when a diagnosis cannot be made with one of them. PMID- 26838482 TI - A retrospective review of safety using a nursing driven protocol for autonomic dysreflexia in patients with spinal cord injuries. AB - OBJECTIVE/BACKGROUND: Autonomic dysreflexia is a potentially life-threatening condition which afflicts a significant proportion of individuals with spinal cord injuries (SCI). To date, the safety and efficacy of several commonly used interventions for this condition have not been studied. DESIGN: A retrospective chart review of the safety of a previously implemented nursing driven inpatient autonomic dysreflexia protocol. METHODS: Seventy-eight male patients with SCI who experienced autonomic dysreflexia while inpatient at our Veterans Affairs SCI unit over a 3-1/2-year period were included. The safety of a nursing driven protocol utilizing conservative measures, nitroglycerin paste, and oral hydralazine was evaluated. OUTCOME MEASURES: Occurrence of adverse events and relative hypotensive events during all episodes treated with the protocol, and efficacy of attaining target blood pressure for all episodes with protocol adherence and for initial episode experienced by each patient. RESULTS: Four hundred forty-five episodes of autonomic dysreflexia were recorded in the study period, with 92% adherence to the protocol. When the protocol was followed, target blood pressure was achieved for 97.6% of all episodes. Twenty-three total adverse events occurred (5.2% of all episodes). All adverse events were due to hypotension and only 0.9% required interventions beyond clinical monitoring. Of each patient's initial autonomic dysreflexia episode, 97.3% resolved using the protocol without need for further escalation of care. CONCLUSION: This inpatient nursing driven-protocol for treating autonomic dysreflexia utilizing conservative measures, nitroglycerin paste and oral hydralazine achieved target blood pressure with a high success rate and a low incidence of adverse events. PMID- 26838484 TI - Development and evaluation of nanoparticles based on mPEG-PLA for controlled delivery of vinpocetine: in vitro and in vivo studies. AB - The aim of present study was to develop VIN-loaded mPEG-PLA nanoparticle systems. The VIN mPEG-PLA nanoparticles were prepared using an emulsion solvent evaporation method, and studied their particle size, morphology, encapsulation efficiency and drug-loading coefficient. Moreover, the nanoparticles were evaluated on the drug release behaviors in vitro and bioavailability in vivo. The results show that the spherical nanoparticles obtained were negatively charged with a zeta potential of about -23.4 mV and characterized ~110 nm with a narrow size distribution. The encapsulation efficiency and drug loading of prepared NPs were 76.4 +/- 6.3 and 9.2 +/- 2.2% (n=5), respectively. The in vitro release showed that the percent of accumulated dissolution of VIN NPs in phosphate buffered saline 6.8 over 24 h was <80%, which was almost 100% of VIN in commercial injections. The in vivo study indicated that systemic absorption of VIN was significantly enhanced by incorporating into mPEG-PLA NPs compared with VIN injection (2.87-fold in AUC0-t). The results suggested that the form of VIN in mPEG-PLA NPs could enter the body circulation to perform sustained release in vitro and in vivo. PMID- 26838483 TI - Ferroelastic switching in a layered-perovskite thin film. AB - A controllable ferroelastic switching in ferroelectric/multiferroic oxides is highly desirable due to the non-volatile strain and possible coupling between lattice and other order parameter in heterostructures. However, a substrate clamping usually inhibits their elastic deformation in thin films without micro/nano-patterned structure so that the integration of the non-volatile strain with thin film devices is challenging. Here, we report that reversible in-plane elastic switching with a non-volatile strain of approximately 0.4% can be achieved in layered-perovskite Bi2WO6 thin films, where the ferroelectric polarization rotates by 90 degrees within four in-plane preferred orientations. Phase-field simulation indicates that the energy barrier of ferroelastic switching in orthorhombic Bi2WO6 film is ten times lower than the one in PbTiO3 films, revealing the origin of the switching with negligible substrate constraint. The reversible control of the in-plane strain in this layered perovskite thin film demonstrates a new pathway to integrate mechanical deformation with nanoscale electronic and/or magnetoelectronic applications. PMID- 26838485 TI - Irritable bowel syndrome (IBS) subtypes: Nothing resembles less an IBS than another IBS. AB - Two new members of "IBS Patient Association" met at a meeting. Feeling somewhat lost, not knowing anybody present, they introduced themselves to each other. After exchanging names, one asks the other - "What's your problem?" The other one answers - "I got constipation that laxatives fail to relieve, and my belly, which is always bloated, sometimes hurts so much that I can't even leave home". Deeply surprised, the first individual inquires - "What are you doing here then?" "Why, I came to this meeting looking for some help for my irritable colon", she answered. "Irritable colon? That's no irritable colon. Irritable bowel syndrome is what I suffer from, and it's diarrhea that won't let me be; can't stop running to the toilet, and cramps just pop up any time". Now both looked surprised. Both thought they had come to the wrong meeting, and both were on the verge of leaving. Luckily, the Association's secretary showed up and explained that both had IBS. PMID- 26838486 TI - Irritable bowel syndrome subtypes: Clinical and psychological features, body mass index and comorbidities. AB - BACKGROUND: Irritable bowel syndrome (IBS) is classified into subtypes according to bowel habit. OBJECTIVE: To investigate whether there are differences in clinical features, comorbidities, anxiety, depression and body mass index (BMI) among IBS subtypes. METHODS: The study group included 113 consecutive patients (mean age: 48 +/- 11 years; females: 94) with the diagnosis of IBS. All of them answered a structured questionnaire for demographic and clinical data and underwent upper endoscopy. Anxiety and depression were assessed by the Hospital Anxiety and Depression scale (HAD). RESULTS: The distribution of subtypes was: IBS-diarrhea (IBS-D), 46%; IBS-constipation (IBS-C), 32%, and mixed IBS (IBS-M), 22%. IBS overlap with gastroesophageal reflux disease (GERD), functional dyspepsia, chronic headache and fibromyalgia occurred in 65.5%, 48.7%, 40.7% and 22.1% of patients, respectively. Anxiety and/or depression were found in 81.5%. Comparisons among subgroups showed that bloating was significantly associated with IBS-M compared to IBS-D (odds ratio-OR-5.6). Straining was more likely to be reported by IBS-M (OR 15.3) and IBS-C (OR 12.0) compared to IBS-D patients, while urgency was associated with both IBS-M (OR 19.7) and IBS-D (OR 14.2) compared to IBS-C. In addition, IBS-M patients were more likely to present GERD than IBS-D (OR 6.7) and higher scores for anxiety than IBS-C patients (OR 1.2). BMI values did not differ between IBS-D and IBS-C. CONCLUSION: IBS-M is characterized by symptoms frequently reported by both IBS-C (straining) and IBS-D (urgency), higher levels of anxiety, and high prevalence of comorbidities. These features should be considered in the clinical management of this subgroup. PMID- 26838487 TI - Predictive factors of small bowel patency in Crohn's disease patients. AB - BACKGROUND: Patency capsule was developed to avoid small bowel video capsule endoscopy retention, namely in patients with Crohn's disease. AIMS: To evaluate the predictive factors of small bowel patency in Crohn's disease patients. PATIENTS AND METHODS: Retrospective analysis including 151 Crohn's disease patients submitted to patency capsule (Agile(r) Patency Capsule) from 2011 to 2012. Patients that excreted the intact patency capsule were classified as having a patent small bowel (without patency capsule retention), other patients were considered to have negative patency of the small bowel (patency capsule retention). RESULTS: Patients had a mean age of 41+/-14 years, 54% were female and 25% had been previously submitted to surgery. Stricturing disease was seen in 20% of cases and penetrating disease in 16% of cases. Left-sided colonic lesions and ileal strictures were observed at colonoscopy in 13% and 9% of patients, respectively. In our sample, 28% of patients had negative patency of the small bowel (patency capsule retention). In multivariate analysis, independent factors that were associated with negative patency of the small bowel in Crohn's disease patients were stricturing (OR 10.16, p < 0.001) and penetrating phenotypes (OR 11.73, p = 0.001), left-sided colonic lesions (OR 3.77, p = 0.038), ileal stricture (OR 9.76, p = 0.003); previous intestinal surgery was found to be protective (OR 0.16, p = 0.006). CONCLUSIONS: Stricturing or penetrating disease, ileal strictures, no previous surgery and left-sided colonic lesions were the factors associated with negative small bowel patency in Crohn's disease patients. PMID- 26838488 TI - Overexpression of Aquaporin 1 on cysts of patients with polycystic liver disease. AB - BACKGROUND AND OBJECTIVE: Polycystic liver disease (PCLD) represents a group of genetic disorders that include autosomal dominant polycystic kidney disease (ADPKD) and isolated polycystic liver disease (iPCLD). There is currently no definitive treatment except for liver transplantation. The aim of this study was to assess the expression level of aquaporin 1 (AQP1) on the PCLD cysts with different sizes and provide the potential therapeutic target. METHODS: We collected 3 normal bile ducts, and recruited 8 patients with simple liver cyst disease, 24 patients with ADPKD, and 17 patients with iPCLD. AQP1 expression in different types of cyst walls and in normal bile ducts was detected using real time quantitative PCR, western blot and immunofluorescence staining. We also compared AQP1 expression levels in cysts of different sizes. Besides, ionic concentrations, pH and osmolality of cyst fluid were analyzed. RESULTS: The results showed that AQP1 expression in PCLD cysts was significantly higher than that in simple liver cysts and the normal bile ducts. In addition, a comparable increasing trend was found in cysts of smaller sizes to cysts of larger sizes. pH values, the sodium and chloride concentrations were higher in cyst fluid than that in the serum. CONCLUSIONS: AQP1 was overexpressed in cystic cholangiocytes. A tendency of increased AQP1 protein expression in correlation with the cyst size was also found. These observations offered a direction into the molecular mechanisms of cyst expansion and maybe provide new treatment strategies to reduce fluid secretion into liver cysts. PMID- 26838489 TI - Idiopathic portal hypertension regarding thiopurine treatment in patients with inflammatory bowel disease. AB - INTRODUCTION: The possibility of developing idiopathic portal hypertension has been described with thiopurine treatment despite compromises the prognosis of these patients, the fact its true prevalence is unknown. MATERIAL AND METHODS: A cross-sectional study was conducted in a cohort of inflammatory bowel disease (IBD) patients followed at our unit, to determine the prevalence of diagnosis of idiopathic portal hypertension (IPH) and its relationship with thiopurine treatment. RESULTS: At the time of the analysis, 927/1,419 patients were under treatment with thiopurine drugs (65%). A total of 4 patients with IBD type Crohn's disease with idiopathic portal hypertension probably related to the thiopurine treatment were identified (incidence of 4.3 cases per 1,000). Seventy five percent of patients started with signs or symptoms of portal hypertension. Only one patient was asymptomatic but the diagnosis of IPH because of isolated thrombocytopenia is suspected. However, note that all patients had thrombocytopenia previously. Abdominal ultrasound with fibroscan, hepatic vein catheterization and liver biopsy were performed on all of them as part of the etiology of portal hypertension. In the abdominal ultrasound, indirect portal hypertension data were observed in all patients (as splenomegaly) cirrhosis was also ruled out. The fibroscan data showed significant liver fibrosis (F2-F3). CONCLUSION: Idiopathic portal hypertension following thiopurine treatment in IBD patients is a rare occurrence, but it must be borne in mind in the differential diagnosis for early diagnosis, especially in patients undergoing thiopurine treatment over a long period. The presence of thrombocytopenia is often the only predictor of its development in the preclinical stage. PMID- 26838491 TI - Management of antiplatelet and anticoagulant therapy for endoscopic procedures: Introduction to novel oral anticoagulants. AB - The development of novel antithrombotic therapy in the past few years and its prescription in patients with cardiovascular and circulatory disease has widened the spectrum of drugs that need to be considered when performing an endoscopic procedure. The balance between the thrombotic risk patients carry due to their medical history and the bleeding risk involved in endoscopic procedures should be thoroughly analyzed by Gastroenterologists. New oral anticoagulants (NOACs) impose an additional task. These agents, that specifically target factor IIa or Xa, do not dispose of an anticoagulation monitoring method nor have an antidote to revert their effect, just as with antiplatelet agents. Understanding the fundamental aspects of these drugs provides the necessary knowledge to determine the ideal period the antithrombotic therapy should be interrupted in order to perform the endoscopic procedure, offering maximum safety for patients and optimal results. PMID- 26838490 TI - Impact of a gluten-free diet on bone mineral density in celiac patients. AB - BACKGROUND: Osteoporosis (OP) is a metabolic bone illness that may complicate celiac disease (CD). It can lead to devastating consequences because of low bone mass and fragility fractures. PURPOSE: To study the OP prevalence in a group of Brazilian patients with CD and the value of a gluten free diet (GFD). METHODS: Retrospective study of celiac female patients from a single University Center followed with bone densitometries. Results from densitometry made at first visit were compared with a second study after a median time of 5 years. During this period, patients were submitted to a GFD according to orientations from special program training. Calcium and vitamin D were prescribed to those patients who did not reach the minimal daily requirement through diet. RESULTS: Forty-one celiac female patients, mean age 46.1 +/- 14.8 years, were included. The prevalence of osteopenia at first visit was 56.1% and that of osteoporosis 29.2%. Osteoporosis was associated with longer disease duration (p = 0.01). The second densitometry was performed in a median time of 5 years (range 1 to 13 years) and disclosed 58.9% osteopenia and 28.2% osteoporosis. The GFD improved bone mass, mainly at (of) spine (comparison of T score with p = 0.03 and of bone mass in g/cm2 with p = 0.02), but it was not sufficient to reduce the number of osteopenic (p = 0.9) and osteoporotic patients (p = 0.4). During the follow up period 25% of osteoporotic patients developed low impact fractures. CONCLUSION: Bone health is notably impaired at baseline in CD patients, especially in those with a diagnostic delay. A GFD modestly improved bone mass density with low impact fractures occurring in one third of patients during the follow up period. PMID- 26838492 TI - Sister Mary Joseph's nodule. PMID- 26838493 TI - Rectosigmoid carcinoma presenting with a large small bowel fistula. PMID- 26838494 TI - Ovarian involvement in Crohn's disease: A rare complication. AB - BACKGROUND: The transmural condition of Crohn's disease predisposes to fistulae or abscesses. The internal fistulae incidence is about 15%. Among them, enteroovarian fistula is rarely described on the literature. Herein, the authors present three cases of enteroovarian fistulas. CASE REPORTS: Two women are diagnosed with ileal Crohn's disease that presented a pelvic abscess diagnosed by ultrasound and CT. On surgery, an inflammatory mass involving the ileum and the ovary was found. The third woman was operated because of a tuboovarian abscess and was diagnosed with ileal Crohn's disease afterwards. In the three cases, the histopathological analysis of the ovary showed granulomas with abscess compatible with Crohn's disease. In one of the cases, multinucleated giant cells were found in the foreign body reaction to vegetable matter. A right ileocolectomy and an adnexectomy were performed in all three cases. No further involvement of the contralateral ovary or other gynaecological complications was observed. DISCUSSION: The treatment of Crohn's disease complications should be individualised. In the case of ovarian involvement, surgical treatment should include adnexectomy. PMID- 26838495 TI - Contribution of infliximab population pharmacokinetic model for dose optimization in ulcerative colitis patients. PMID- 26838496 TI - Primary omental torsion as presentation of acute abdomen. Case report. PMID- 26838497 TI - On an imported case of Taenia saginata. PMID- 26838498 TI - Celiac disease and fibromyalgia: Is there an association? AB - It has been found that celiac disease (CD) and non-celiac gluten sensitivity (NCGS) have a high prevalence in fibromyalgia (FM) patients. NCGS is a relatively new entity characterized by gastrointestinal and extra-intestinal manifestations in the absence of CD or wheat allergy. It is different from CD because anti transglutaminase (anti-tTG) or endomysial antibodies (IgA-EmA) are lacking and the intestinal mucosa is normal or with mild abnormalities as increased intraepithelial lymphocytes in the absence of villous atrophy. PMID- 26838499 TI - Gastric neuroendocrine tumor presenting with gastrointestinal bleeding. PMID- 26838500 TI - A propos of a case: Abdominal compartment syndrome caused by massive hydatid disease. PMID- 26838502 TI - GPs call for an end to CQC inspections. PMID- 26838503 TI - Fixed-route monitoring and a comparative study of the occurrence of herbicide resistant oilseed rape (Brassica napus L.) along a Japanese roadside. AB - Previously, we conducted a roadside survey to reveal the occurrence of genetically modified (GM) oilseed rape along a Japanese roadside (Route 51). In this study, we performed successive and thorough fixed-route monitoring in 5 sections along another road (Route 23). Oilseed rape plants were detected on both sides of the road in each section between autumn 2009 and winter 2013, which included 3 flowering seasons. In four sections, more plants were found on the side of the road leading from the Yokkaichi port than on the opposite side. In the fifth section, the presence of clogged drains on the roadside, where juvenile plants concentrated, caused the opposite distribution: oilseed rape predominantly occurred along the inbound lanes (leading to the Yokkaichi port) in 2010 and 2012. Unlike in our previous survey, glyphosate- or glufosinate-resistant oilseed rape plants were abundant (>75% of analyzed plants over 3 years). Moreover, a few individuals bearing both herbicide resistance traits were also detected in some sections. The spillage of imported seeds may explain the occurrence of oilseed rape on the roadside. The abundance of herbicide-resistant oilseed rape plants may reflect the extent of contamination with GM oilseed rape seed within imports. PMID- 26838501 TI - Evolutionary analysis across mammals reveals distinct classes of long non-coding RNAs. AB - BACKGROUND: Recent advances in transcriptome sequencing have enabled the discovery of thousands of long non-coding RNAs (lncRNAs) across many species. Though several lncRNAs have been shown to play important roles in diverse biological processes, the functions and mechanisms of most lncRNAs remain unknown. Two significant obstacles lie between transcriptome sequencing and functional characterization of lncRNAs: identifying truly non-coding genes from de novo reconstructed transcriptomes, and prioritizing the hundreds of resulting putative lncRNAs for downstream experimental interrogation. RESULTS: We present slncky, a lncRNA discovery tool that produces a high-quality set of lncRNAs from RNA-sequencing data and further uses evolutionary constraint to prioritize lncRNAs that are likely to be functionally important. Our automated filtering pipeline is comparable to manual curation efforts and more sensitive than previously published computational approaches. Furthermore, we developed a sensitive alignment pipeline for aligning lncRNA loci and propose new evolutionary metrics relevant for analyzing sequence and transcript evolution. Our analysis reveals that evolutionary selection acts in several distinct patterns, and uncovers two notable classes of intergenic lncRNAs: one showing strong purifying selection on RNA sequence and another where constraint is restricted to the regulation but not the sequence of the transcript. CONCLUSION: Our results highlight that lncRNAs are not a homogenous class of molecules but rather a mixture of multiple functional classes with distinct biological mechanism and/or roles. Our novel comparative methods for lncRNAs reveals 233 constrained lncRNAs out of tens of thousands of currently annotated transcripts, which we make available through the slncky Evolution Browser. PMID- 26838504 TI - Molecular Pathology of the Breast. AB - Information focuses on molecular pathology of breast cancer. Presented are clinical features of breast cancer, detailed discussion of histology and molecular pathology for invasive ductal carcinoma, invasive lobular carcinoma, other subtypes of invasive breast cancer, and breast cancer progression and precursors. Phenotypes and genotypes of breast cancer are presented, along with the role of biomarkers, gene profiling, and hormone receptors. Targeted therapies and prognostic indicators are presented with practical applications of molecular pathology for the surgical pathologist. PMID- 26838505 TI - Molecular Pathology of Gastrointestinal Cancer. AB - The purpose of this review is to discuss important molecular changes that aid decision making in patient management and play a role in emerging treatment strategies for gastrointestinal malignancies. Although screening and surveillance practices have had an impact on the natural history of some tumor types, gastric carcinoma is a major cause of morbidity and mortality in high prevalence regions and colorectal carcinoma is still the fourth leading cause of cancer related death in the United States. PMID- 26838506 TI - Molecular Pathology of Bladder Cancer. AB - This article focuses on several promising candidate biomarkers that may soon make their transition to the realm of clinical management of bladder cancer. Presented are superficial and muscle-invasive urothelial carcinoma of the bladder and the genetic tests currently available in testing for diagnosis and prognosis of these diseases. PMID- 26838507 TI - Molecular Pathology of Malignant Lymphoma. AB - This review focuses on practical uses of molecular testing in mature B-cell and T cell lymphomas with a focus on those lymphomas in which molecular testing is common. Clinical findings, histology, and biomarkers, as well as diagnostic and prognostic predictive value and practical applications of molecular testing for mature B- and T-cell lymphomas are presented. PMID- 26838508 TI - Molecular Pathology of Non-Small Cell Lung Cancer. AB - This review offers an overview of the molecular pathology of lung cancer, with a focus on analyses that are most commonly part of the current clinical testing paradigm. Molecular testing of lung cancer has proved integral to the success of new targeted therapies, and their use is now commonplace in treatment selection. Traditional pathologic evaluation, however, plays a major role in these advances and serves an equally critical role to aid in determining optimal therapy. PMID- 26838509 TI - Pathology and Genetics of Pancreatic Neoplasms. AB - This is a state-of-the-art review of the molecular genetics of pancreatic neoplasms. Although understanding of the molecular features underlying pancreatic neoplasms is still in its infancy, a strong emphasis on the relevance of these findings for the practicing surgical pathologist is provided. The application of molecular techniques has yielded a wealth of information that may soon enhance diagnostics, and will also lead to the development of safer, more effective targeted therapies. The pathologist will play a key role in integrating the current pathologic classification system with newly validated molecular markers. PMID- 26838510 TI - Molecular Pathology of Sarcoma. AB - The rapid growth of tissue-based molecular pathology has changed the practice of the surgical pathologist signing out soft tissue tumors. This information is presented in a practical and succinct manner focusing on clinically validated findings that have diagnostic or therapeutic relevance. The approach is morphologically based and focuses on differential diagnoses and clinical scenarios. Molecular techniques can be an invaluable ancillary tool. PMID- 26838511 TI - The Molecular Pathology of Salivary Gland Tumors with Translocations. AB - Presented here are the salivary gland tumors now recognized to have significant and highly prevalent translocations. These include both common and uncommon malignancies: mucoepidermoid carcinoma, adenoid cystic carcinoma, mammary analog secretory carcinoma, and clear cell carcinoma. These mutations have potential diagnostic applications, particularly in difficult and challenging variant morphologies are unusually challenging differential diagnoses. Practical applications of the molecular pathology of these tumors is discussed. The mutational assessment may also prove to have therapeutic importance, as targeted therapies may be generated for these tumors in the future. PMID- 26838512 TI - Practical Applications of Molecular Pathology. PMID- 26838513 TI - Visible light photoswitching of conjugated polymer nanoparticle fluorescence. AB - Conjugated polymer nanoparticles doped with a reverse photochromic dye exhibit highly quenched fluorescence that can be reversibly activated by controlling the form of the photochrome with visible light. PMID- 26838514 TI - Frequent detection of transcriptionally active Felis catus papillomavirus 2 in feline cutaneous squamous cell carcinomas. AB - Felis catus papillomavirus 2 (FcaPV-2) causes premalignant skin lesions in cats and has also been found in a proportion of cutaneous squamous cell carcinomas (SCCs) - a common and potentially fatal cancer of cats. Whilst this could suggest a role of the virus in cancer development, FcaPV-2 has also been detected in skin swabs of normal cats, making it difficult to discern whether the papillomavirus is causing the cancer or merely an 'innocent bystander'. To distinguish between these two possibilities, real-time PCR was used to determine the viral copy number and the transcriptional activity of FcaPV-2 infections present in 70 formalin-fixed paraffin-embedded skin lesions including 10 papillomavirus-induced premalignant lesions and 60 SCCs. FcaPV-2 gene expression was found in 21 of 60 (35 %) SCCs, all 10 premalignant lesions and none of 10 normal skin samples. The results showed two distinct subsets of SCCs. The majority of the SCCs had low copy numbers of FcaPV-2 DNA (mean of 17 copies per copy of reference gene DNA) and no FcaPV-2 gene expression, suggesting the virus was an incidental finding. In contrast, 20 SCCs had detectable FcaPV-2 E6/E7 gene expression and very high copy numbers of FcaPV-2 DNA, with a mean of 32 930 copies per copy of reference gene DNA. The relative quantity of E6/E7 gene expression and the viral copy number in this group were similar to those found in the papillomavirus-induced premalignant lesions, suggesting that FcaPV-2 may play a role in the development of a subset of feline cutaneous SCCs. PMID- 26838515 TI - Seroprevalence of West Nile and Usutu viruses in military working horses and dogs, Morocco, 2012: dog as an alternative WNV sentinel species? AB - A serosurvey of 349 military working horses and 231 military working dogs was conducted in ten sites in Morocco in 2012. This survey revealed a high level of exposure of these animals to flaviviruses: seroprevalence rates of 60% in horses and of 62% in dogs were observed using a competitive West Nile virus (WNV) enzyme linked immunosorbent assay (cELISA). Seroneutralization test results showed that the majority of cELISA-positive results were due to exposure to WNV. Further assays conducted in vaccinated horses with a DIVA (Differentiating Infected from Vaccinated Animals) test indicated that anti-WNV antibodies had been stimulated through WNV natural infection. Moreover, in both species, seroneutralization tests suggested an exposure to Usutu virus (USUV). Data analysis did not show any significant difference of cELISA seropositivity risk between horses and dogs. Dogs may thus represent an interesting alternative to equines for the serological surveillance of WNV or USUV circulation, especially in areas where equine vaccination precludes passive surveillance (based on the detection of West Nile fever cases) in horses. PMID- 26838517 TI - Early evidence for the role of TRIM29 in multiple cancer models. PMID- 26838516 TI - Nanoparticle-mediated photothermal effect enables a new method for quantitative biochemical analysis using a thermometer. AB - A new biomolecular quantitation method, nanoparticle-mediated photothermal bioassay, using a common thermometer as the signal reader was developed. Using an immunoassay as a proof of concept, iron oxide nanoparticles (NPs) captured in the sandwich-type assay system were transformed into a near-infrared (NIR) laser driven photothermal agent, Prussian blue (PB) NPs, which acted as a photothermal probe to convert the assay signal into heat through the photothermal effect, thus allowing sensitive biomolecular quantitation using a thermometer. This is the first report of biomolecular quantitation using a thermometer and also serves as the first attempt to introduce the nanoparticle-mediated photothermal effect for bioassays. PMID- 26838519 TI - [Rare rheumatic diseases]. PMID- 26838521 TI - [Lung cancer and rheumatoid arthritis. An interdisciplinary challenge]. AB - Lung cancer is a frequently occurring disease, particularly in the elderly; however, within the last 10 years the pharmaceutical treatment of lung cancer has been significantly improved. Due to a better understanding of the pathophysiological events and the identification of molecular subgroups of lung tumors, new therapeutic drugs have been developed that significantly prolong survival of patients with the respective molecular pattern. In particular immunotherapeutic agents, such as programmed death-ligand 1 (PD-L1) and programmed death 1 (PD1) antibodies have shown promising clinical results in a subgroup of lung cancer patients. Due to the high incidence of both lung cancer and rheumatic diseases they often occur together, which necessitates an interdisciplinary management. The success of improved therapy of lung cancer has led to a greater focus on the treatment of comorbidities; however, interventions into the immune system by immune checkpoint inhibitors can lead to new challenges when an autoimmune disease is simultaneously present. The possibility of an effective screening for lung cancer in the future also presents the prospect of an improvement in mortality, which raises the question of the optimal monitoring of patients with rheumatoid arthritis (RA) under immunosuppressive therapy. The aim of this review is to discuss the interaction between lung cancer and RA with respect to the currently available data. PMID- 26838522 TI - Lewis-Sumner syndrome associated with infliximab therapy in ulcerative colitis. PMID- 26838523 TI - Application of electrophysiological methods and magnetic resonance tomographic angiography in the differentiation between hemifacial spasm and Meige syndrome. AB - Bilateral hemifacial spasm and Meige syndrome can be easily confused due to their similar clinical manifestation. Here, we aimed to investigate the application of electrophysiological methods and magnetic resonance tomographic angiography (MRTA) in the differentiation between hemifacial spasm and Meige syndrome. 10 patients with bilateral hemifacial spasm and 9 patients with Meige syndrome received electrophysiological monitoring of nerves. There were two males and eight females with bilateral hemifacial spasm, aged 16-58 years with a course of 5-54 months. For the patients with Meige syndrome, there were three males and six females, aged 51-68 years with a course of 12-36 months. All patients received conventional MRTA of the brain blood vessels before decompression. We found that all patients with Meige syndrome showed synchronous contraction of bilateral orbicularis oculi muscles and (or) burst discharge from orbicularis oris muscles in surface electromyography (sEMG). However, those with hemifacial spasm presented with bilaterally asynchronous burst discharge. Electromyography for patients with Meige syndrome did not record abnormal muscle response (AMR), but recorded AMR for those with bilateral hemifacial spasm. The offending vessels were compressed in patients with hemifacial spasm in MRTA, while MRTA results were generally negative for those with Meige syndrome. Combining sEMG and AMR detection in EMG and MRTA, bilateral hemifacial spasm can be differentiated from Meige syndrome with a reduction of misdiagnosis rate. PMID- 26838524 TI - Ultra-low Doping on Two-Dimensional Transition Metal Dichalcogenides using DNA Nanostructure Doped by a Combination of Lanthanide and Metal Ions. AB - Here, we propose a novel DNA-based doping method on MoS2 and WSe2 films, which enables ultra-low n- and p-doping control and allows for proper adjustments in device performance. This is achieved by selecting and/or combining different types of divalent metal and trivalent lanthanide (Ln) ions on DNA nanostructures, using the newly proposed concept of Co-DNA (DNA functionalized by both divalent metal and trivalent Ln ions). The available n-doping range on the MoS2 by Ln-DNA is between 6 * 10(9) and 2.6 * 10(10 ) cm(-2). The p-doping change on WSe2 by Ln DNA is adjusted between -1.0 * 10(10) and -2.4 * 10(10 ) cm(-2). In Eu(3+) or Gd(3+)-Co-DNA doping, a light p-doping is observed on MoS2 and WSe2 (~10(10 ) cm( 2)). However, in the devices doped by Tb(3+) or Er(3+)-Co-DNA, a light n-doping (~10(10 ) cm(-2)) occurs. A significant increase in on-current is also observed on the MoS2 and WSe2 devices, which are, respectively, doped by Tb(3+)- and Gd(3+)-Co-DNA, due to the reduction of effective barrier heights by the doping. In terms of optoelectronic device performance, the Tb(3+) or Er(3+)-Co-DNA (n doping) and the Eu(3+) or Gd(3+)-Co-DNA (p-doping) improve the MoS2 and WSe2 photodetectors, respectively. We also show an excellent absorbing property by Tb(3+) ions on the TMD photodetectors. PMID- 26838525 TI - In a Neonatal Piglet Model of Intestinal Failure, Administration of Antibiotics and Lack of Enteral Nutrition Have a Greater Impact on Intestinal Microflora Than Surgical Resection Alone. AB - BACKGROUND: Data are limited on how short bowel syndrome (SBS) affects the healthy developing intestinal microbiome, with even less assessing different SBS anatomical surgical models. This study was conducted to describe the "ileal" and "colonic" microflora in 2 surgical models of SBS. MATERIALS AND METHODS: Neonatal piglets (2-5 days old) underwent intestinal resection, leaving the ileum (JI anatomy, n = 6) or removing the ileum and ileocecal valve (JC anatomy, n = 5), or sham surgery (sham; n = 4). JI, JC, and sham piglets commenced parenteral nutrition on day 0 and received ampicillin and trimethoprim-sulfadoxine on days 0 4 for prevention of line sepsis. At day 7, ileal and colonic digesta were collected, and they were also collected from age-matched sow-fed piglets (n = 6). DNA extraction, sequencing, and annotation followed standard procedures. RESULTS: Colonic and ileal bacterial genus diversity and relative bacterial abundance were greater ( P < .05) in sow-fed compared with JI, JC, and sham piglets; however, minor differences were observed in either location between sham, JI, and JC piglets and within the surgical model. In the colon, sow-fed piglets had higher ( P < .05) abundance of Lactobacillus (26%) and tended to have lower ( P = .06) abundance of Enterococcus (<.1%) than JI, JC, or sham piglets, in which Lactobacillus and Enterococcus abundance averaged <.1% and 9%, respectively. CONCLUSIONS: Intestinal resection reduces bacterial diversity in the large bowel, and the difference is associated with the presence/absence of the ileum and ileocecal valve. The lack of enteral nutrition and antibiotic administration (ie, sow-fed vs surgery) had a greater influence on the observed shift in diversity and relative abundance than intestinal resection. PMID- 26838527 TI - Association of Serum Phosphate Levels and Anemia in Critically Ill Surgical Patients. AB - BACKGROUND: Deranged serum phosphate (Phos) levels are associated with anemia in hospitalized patients, but their relevance to critical illness is unclear. Therefore, our goal was to investigate whether abnormal Phos on admission to the surgical intensive care unit (ICU) is associated with anemia. MATERIALS AND METHODS: We performed a retrospective analysis of data from an ongoing study of nutrition in critical illness. Serum Phos and hemoglobin levels were obtained at ICU admission. Normal Phos was defined as 2.5-4.0 mg/dL. To investigate the association between Phos and anemia, we performed logistic regression analyses, while controlling for age, sex, race, body mass index, Nutrition Risk Screening score, Deyo-Charlson Comorbidity Index, creatinine, mean corpuscular volume, and serum albumin. RESULTS: In total, 510 patients comprised the analytic cohort; 62% were anemic, 30% had Phos >4.0 mg/dL, and 14% had levels <2.5 mg/dL. Logistic regression analysis demonstrated each unit increment in Phos was associated with a 25% higher likelihood of anemia (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.04-1.50). Moreover, patients with Phos >4.0 mg/dL had a 68% higher likelihood of anemia compared with those with normal levels (OR, 1.68; 95% CI, 1.02-2.80). Patients with Phos <2.5 mg/dL were not more likely to be anemic compared with those with normal levels. CONCLUSION: Surgical ICU patients with admission Phos >4.0 mg/dL are more likely to be anemic compared with those with normal levels. Our findings support the need for studies to determine whether globally maintaining optimal Phos reduces the likelihood of anemia and whether ideal Phos during acute care hospitalization influences clinical outcomes. PMID- 26838526 TI - Long-Term Body Composition Changes in Women Following Roux-en-Y Gastric Bypass Surgery. AB - BACKGROUND: Although most individuals experience successful weight loss following Roux-en-Y gastric bypass (RYGB), weight regain is a concern, the composition of which is not well documented. Our aim was to evaluate changes in body composition and handgrip strength as a measure of functional status in participants from a previous 1-year post-RYGB longitudinal study who had undergone RYGB approximately 9 years prior. METHODS: Five women from an original larger cohort were monitored pre-RYGB and 1.5 months, 6 months, 1 year, and 9 years post-RYGB. Body composition was assessed at all time points using dual energy x-ray absorptiometry and multiple dilution. Handgrip strength was measured using a digital isokinetic hand dynamometer (Takei Scientific Instruments, Ltd, Tokyo, Japan). RESULTS: Mean time to final follow-up was 8.7 years. Lean soft tissue (LST) loss over the ~9-year period was on average 11.9 +/- 5.6 kg. Compared with 1-year post-RYGB, 9-year LST was 4.4 +/- 3.0 kg lower ( P = .03). Fat-free mass decreased over the 9-year period by 12.6 +/- 5.8 kg. Mean fat mass (FM) decreased from 75.4 +/- 22.6 kg pre-RYGB to 35.5 +/- 21.5 kg 1 year post-RYGB but then trended toward an increase of 8.6 +/- 7.0 kg between 1 year and 9 years post-RYGB ( P = .053). Loss of LST was correlated with loss of handgrip strength ( r = 0.64, P = .0005). CONCLUSION: The continued loss of lean mass associated with decreased handgrip strength occurring with long-term trend toward FM regain post RYGB is concerning. The loss of LST and functional strength carries particular implications for the aging bariatric population and should be investigated further. PMID- 26838528 TI - Should We Increase Protein Delivery During Critical Illness? PMID- 26838531 TI - Dysplastic Nevi. AB - Patients with multiple dysplastic nevi have an increased risk for malignant melanoma, and dysplastic nevi themselves have at least some potential for malignant transformation. Development of malignant melanoma is uncommon within dysplastic nevi, however. Since this transformation occurs in other types of nevi, their role as a marker of increased risk for melanoma in the patients who bear them seems to be of greater significance. This article discusses the gross, clinical and microscopic features; diagnosis; and prognosis of dysplastic nevi. The key features and pitfalls of diagnosing malignant melanoma, congenital nevus, and recurrent nevus are given. PMID- 26838530 TI - Association Between Malnutrition and Clinical Outcomes in the Intensive Care Unit: A Systematic Review [Formula: see text]. AB - Malnutrition is associated with poor clinical outcomes among hospitalized patients. However, studies linking malnutrition with poor clinical outcomes in the intensive care unit (ICU) often have conflicting findings due in part to the inappropriate diagnosis of malnutrition. We primarily aimed to determine whether malnutrition diagnosed by validated nutrition assessment tools such as the Subjective Global Assessment (SGA) or Mini Nutritional Assessment (MNA) is independently associated with poorer clinical outcomes in the ICU and if the use of nutrition screening tools demonstrate a similar association. PubMed, CINAHL, Scopus, and Cochrane Library were systematically searched for eligible studies. Search terms included were synonyms of malnutrition, nutritional status, screening, assessment, and intensive care unit. Eligible studies were case control or cohort studies that recruited adults in the ICU; conducted the SGA, MNA, or used nutrition screening tools before or within 48 hours of ICU admission; and reported the prevalence of malnutrition and relevant clinical outcomes including mortality, length of stay (LOS), and incidence of infection (IOI). Twenty of 1168 studies were eligible. The prevalence of malnutrition ranged from 38% to 78%. Malnutrition diagnosed by nutrition assessments was independently associated with increased ICU LOS, ICU readmission, IOI, and the risk of hospital mortality. The SGA clearly had better predictive validity than the MNA. The association between malnutrition risk determined by nutrition screening was less consistent. Malnutrition is independently associated with poorer clinical outcomes in the ICU. Compared with nutrition assessment tools, the predictive validity of nutrition screening tools were less consistent. PMID- 26838529 TI - Preventing the Progression of Intestinal Failure-Associated Liver Disease in Infants Using a Composite Lipid Emulsion: A Pilot Randomized Controlled Trial of SMOFlipid. AB - BACKGROUND: To examine whether SMOFlipid prevents progression of intestinal failure-associated liver disease (IFALD) in parenteral nutrition (PN)-dependent infants with early IFALD (conjugated bilirubin 17-50 umol/L, 1-3 mg/dL). STUDY DESIGN: Pilot multicenter blinded randomized controlled trial comparing SMOFlipid with Intralipid. Patients received the trial lipid for up to 12 weeks, unless they achieved full enteral tolerance sooner. The primary clinical outcome was the serum conjugated bilirubin. RESULTS: Twenty-four infants (mean age, 6 weeks) participated in the trial (13 Intralipid and 11 SMOFlipid). At the time of trial enrollment, patients in both groups were receiving 90% of their calories by PN. Mean duration on trial was 8 weeks and did not differ according to treatment ( P = .99). At trial conclusion, patients who received SMOFlipid had a lower conjugated bilirubin than those who received Intralipid (mean difference, -59 umol/L; P = .03). Patients receiving SMOFlipid were also more likely to have a decrease in serum conjugated bilirubin to 0 umol/L than those in the Intralipid group over the entire observation period (hazard ratio, 10.6; 95%; P = .03). The time to achievement of full enteral tolerance did not differ statistically (hazard ratio, 1.3; P = .59) between the groups. There was no significant difference in safety outcomes between the groups. CONCLUSIONS: Compared with Intralipid, SMOFlipid reduces the risk of progressive IFALD in children with intestinal failure. This trial was registered at clinicaltrials.gov as NCT00793195. PMID- 26838532 TI - Congenital Melanocytic Nevi. AB - This article reviews congenital melanocytic nevi (CMN), which are present at birth or appear shortly thereafter, and their main histologic features. Several histologic variants and histopathologic criteria that differentiate CMN from other nevi, such as atypical or dysplastic nevi, and from nevoid malignant melanoma, are discussed. Histologic pitfalls in the correct identification of lentiginous melanocytic hyperplasia, pagetoid scatter, and proliferative nodules in the context of CMN are discussed. The risk for development of malignant melanoma in association with a congenital melanocytic nevus and variable causes for changing mole are discussed. PMID- 26838533 TI - Nevi of Special Sites. AB - Melanocytic nevi can have a wide range of histologic appearances. Within the spectrum of nevi, there exists a group that presents in certain anatomic locations with histologically worrisome features but nonetheless benign behavior. This group of nevi has been broadly categorized as nevi of special sites. The anatomic locations affected by this group include the embryonic milkline (breast, axillae, umbilicus, genitalia), flexural areas, acral surfaces, ear, and scalp. Nevi in these locations may be mistaken for melanomas because of their histologic appearance, resulting in inappropriate overtreatment of patients. In this article, the authors review the histologic features of these special site nevi and discuss the criteria that help distinguish them from melanoma. PMID- 26838534 TI - Blue Nevi and Related Tumors. AB - Blue nevi and related lesions are characterized by the proliferation of dermal dendritic melanocytes. Although they share certain common clinical and histologic features, they encompass a spectrum of lesions ranging from benign melanocytic hamartomas and common blue nevi to borderline malignant pigmented epithelioid melanocytoma and aggressive malignant blue nevi. This article succinctly describes the common dermal dendritic proliferations and updates readers on newly classified entities and variants. The differential diagnosis of the main entities and strategies to distinguish them from their melanocytic and nonmelanocytic mimics is also presented. PMID- 26838535 TI - Spitz Nevi, Atypical Spitzoid Neoplasms, and Spitzoid Melanoma. AB - Spitz nevi and melanoma represent benign and malignant counterparts commonly coupled in the same differential diagnosis. The precise distinction between the two entities remains an ongoing challenge in dermatopathology and surgical pathology. In past years, considerable work has been devoted to the assembly of criteria to permit exact diagnosis. Although diagnostic accuracy has improved, many lesions remain challenging to classify based solely upon conventional microscopic criteria. In this article, the clinical and histopathological attributes of Spitz nevi and spitzoid melanoma are reviewed. Lesions that cannot be definitively classified based solely upon conventional microscopic criteria are referred to as atypical spitzoid neoplasms, which the authors view as a provisional diagnostic category rather than as a formal disease entity. Molecular assessment by way of comparative genomic hybridization or fluorescence in situ hybridization is increasingly used to facilitate assessment of this challenging differential and is especially germane to the evaluation of ambiguous lesions. PMID- 26838536 TI - Desmoplastic Melanoma. AB - Desmoplastic melanoma (DM) is a variant of spindle cell melanoma characterized by the presence of abundant fibrous matrix. It is typically found in the head and neck region on chronically sun-damaged skin of older individuals. Early detection is uncommon, because its clinical features are not distinctive. DM is prone to misdiagnosis not only clinically but also histologically. It may simulate a sclerosing melanocytic nevus and various benign and malignant nonmelanocytic lesions. Among melanomas said to be desmoplastic by various pathologists there is significant variation with regard to the extent of intratumoral fibrosis. It may be prominent throughout the entire tumor (pure DM) or represent a portion of an otherwise nondesmoplastic melanoma (combined DM). Immunophenotypically, DM are usually strongly and homogeneously positive for S-100 protein, but are often negative or only focally positive for melanocyte differentiation antigens. DM differs from conventional melanoma in its clinical course. It is associated with a higher tendency for local recurrence, but metastases to regional lymph nodes are less common. PMID- 26838537 TI - Nevoid Melanoma. AB - This article discusses the key features of nevoid melanoma. Gross features, microscopic features, immunohistochemistry, differential diagnosis, diagnosis, prognosis, and treatment are also discussed. PMID- 26838538 TI - Acral Lentiginous Melanoma. AB - Acral lentiginous melanoma is an uncommon skin malignancy that occurs with equal frequency in all races and has a worse prognosis than other types of melanoma; it presents as dark, irregular macules, papules, or nodules on the feet and, less commonly, the hands. The histologic findings of acral lentiginous melanoma are characterized by an asymmetric, poorly circumscribed proliferation of continuous single melanocytes at the dermoepidermal junction. Single melanocytes predominate over nests. The tumor must be distinguished from benign acral lentiginous nevi, which can display site-related atypia. PMID- 26838539 TI - Melanoma Margin Assessment. AB - Primary cutaneous melanoma is treated by excisional surgery and careful histologic assessment of the specimen margins is a crucial component of pathology reporting. Surgical margins may be assessed by conventional transverse (bread loaf) vertical sections, by en face vertical sections, or by en face oblique sections. Transverse techniques only sample a small percentage of the surgical margin. En face techniques are technically challenging but allow assessment of close to 100% of the margin. Margin assessment for melanoma removed from chronically sun-damage skin is difficult. Melanoma in situ shows contiguous melanocyte growth, nesting, or intraepidermal pagetoid spread. Pitfalls include solar melanocytic hyperplasia, solar lentigines, melanocytic hyperplasia secondary to previous biopsy, lichenoid reactions, and invasive melanoma mimicking scar or benign nevus. En face sections can be used to assess margins for melanoma on sun-damaged skin, and evidence suggests that frozen sections may also be employed by experienced clinicians. Immunohistochemistry is a useful ancillary technique, enabling more accurate identification of in situ melanoma within a surgical margin. PMID- 26838540 TI - Sentinel Lymph Nodes in Cutaneous Melanoma. AB - Examination of sentinel lymph nodes (SLN) has probably become the most popular method of early staging of patients who have cutaneous melanoma because SLN are considered to be the lymph nodes most likely to contain metastatic deposits; they can be examined in a more intense manner than in standard lymphadenectomy. There are several protocols to examine SLN but most of them use formalin-fixed, paraffin-embedded sections stained with hematoxylin and eosin with the addition of immunohistochemistry. By using these protocols, approximately 20% of patients who have cutaneous melanoma have melanoma cells in the SLN. Current studies are evaluating the possible therapeutic value of removal of positive SLN, but it is accepted by most authors that detection of positive SLN conveys an impaired prognosis for patients who have cutaneous melanoma. PMID- 26838541 TI - Molecular Aspects of Melanoma. AB - Melanoma is the most serious type of skin cancer. Unfortunately, treatment has progressed little and advanced melanoma has appalling survival rates. A goal of molecular analysis is to fully describe the alterations that underpin melanoma's clinical phenotype so that diagnosis can be more accurate, outcome can be predicted with greater confidence, and treatment that is tailored to the patient can be given. This article describes the handful of "signature" changes that are known to occur, describes how some recent studies have shed light on changes beyond this signature, and finally discusses the impact of molecular pathology for practicing histopathologists. PMID- 26838542 TI - Preface. PMID- 26838543 TI - Hanging on by a thread: a rare case of secondary pseudoainhum. AB - Pseudoainhum is a rare and poorly characterised phenomenon involving autoamputation of a digit associated with an identifiable or related disease process. We describe the case of a 19-year-old man with long-standing neurodisability, sensorineural hearing loss and severe keratoderma, presenting with painless rapidly-progressing autoamputation of his left little toe. Genetic analysis thus far has been inconclusive. The toe appeared to be hanging on by a thread, with no clinical signs of infection. Radiographs showed lysis with complete resorption of the proximal phalynx. Routine blood tests found an isolated neutropenia with normal C reactive protein and biochemistry. We report an unusual case of a young adult with a history of chronic neurological and dermatological problems presenting with secondary pseudoainhum and provide a valuable addition to the limited literature describing this rare condition. PMID- 26838544 TI - Transitional hydrogen bonds in aqueous perchlorate solution. AB - Different mechanisms of H-bond formation between perchlorate anions and water are presented using the molecular dynamics simulations. The detailed methods in searching for multi-centered hydrogen bonds are proposed. The time evolution of H bond geometric parameters for classical, bifurcated and trifurcated hydrogen bonds in the aqueous perchlorate solution indicates the transitional character of hydrogen bridges as well as the rigid nature of the solvation structure formed by the ion and its first solvation shell. This is supported by the values of free energy binding of water to perchlorate ions determined for particular types of hydrogen bridges. PMID- 26838545 TI - Abdominal pain in a 31 year old woman. PMID- 26838547 TI - Estimation of hurdle clearance parameters using a monocular human motion tracking method. AB - This paper presents a method of monocular human motion tracking for estimation of hurdle clearance kinematic parameters. The analysis involved 10 image sequences of five hurdlers at various training levels. Recording of the sequences was carried out under simulated starting conditions of a 110 m hurdle race. The parameters were estimated using the particle swarm optimization algorithm and they are based on analysis of the images recorded with a 100 Hz camera. The proposed method does not involve using any special clothes, markers, inertial sensors, etc. As the quality criteria, the mean absolute error and mean relative error were used. The level of computed errors justifies the use of this method to estimate hurdle clearance parameters. PMID- 26838546 TI - Promotion of mitotic catastrophe via activation of PTEN by paclitaxel with supplement of mulberry water extract in bladder cancer cells. AB - Paclitaxel is a mitotic inhibitor used in cancer chemotherapy. Mulberry fruit is rich in phenolic compounds and flavonoids and exhibits chemopreventive activities. In this study, mulberry water extract (MWE) was used as a supplement to synergize with the effects of paclitaxel in the treatment of the TSGH 8301 human bladder cancer cell line. Treatment with paclitaxel combined with MWE (paclitaxel/MWE) enhanced the cytotoxicity of paclitaxel and induced severe G2/M arrest, mitotic catastrophe and subsequent apoptosis, as shown by MTT assay, HE staining and flow cytometry analyses. Differences in the expression and activation of Aurora A and Plk1 between cells treated with paclitaxel/MWE and paclitaxel alone suggested that the combined treatment caused a defect in the early steps of cytokinesis. Paclitaxel/MWE decreased EEA1 immunofluorescence staining and increased the expression of PTEN, indicating that the regimen inhibited the formation of the recycling endosome, which is required for cytokinesis. Paclitaxel/MWE also retarded tumor growth in a TSGH 8301 xenograft model via activation of PTEN and Caspase 3. These data demonstrated a synergistic effect on the anticancer efficacy of paclitaxel through MWE supplementation by promoting mitotic catastrophe through the activation of PTEN, providing a novel and effective therapeutic option for bladder cancer treatment strategies. PMID- 26838549 TI - Context-specific flow through the MEK/ERK module produces cell- and ligand specific patterns of ERK single and double phosphorylation. AB - The same pathway, such as the mitogen-activated protein kinase (MAPK) pathway, can produce different cellular responses, depending on stimulus or cell type. We examined the phosphorylation dynamics of the MAPK kinase MEK and its targets extracellular signal-regulated kinase 1 and 2 (ERK1/2) in primary hepatocytes and the transformed keratinocyte cell line HaCaT A5 exposed to either hepatocyte growth factor or interleukin-6. By combining quantitative mass spectrometry with dynamic modeling, we elucidated network structures for the reversible threonine and tyrosine phosphorylation of ERK in both cell types. In addition to differences in the phosphorylation and dephosphorylation reactions, the HaCaT network model required two feedback mechanisms, which, as the experimental data suggested, involved the induction of the dual-specificity phosphatase DUSP6 and the scaffold paxillin. We assayed and modeled the accumulation of the double phosphorylated and active form of ERK1/2, as well as the dynamics of the changes in the monophosphorylated forms of ERK1/2. Modeling the differences in the dynamics of the changes in the distributions of the phosphorylated forms of ERK1/2 suggested that different amounts of MEK activity triggered context specific responses, with primary hepatocytes favoring the formation of double phosphorylated ERK1/2 and HaCaT A5 cells that produce both the threonine phosphorylated and the double-phosphorylated form. These differences in phosphorylation distributions explained the threshold, sensitivity, and saturation of the ERK response. We extended the findings of differential ERK phosphorylation profiles to five additional cultured cell systems and matched liver tumor and normal tissue, which revealed context-specific patterns of the various forms of phosphorylated ERK. PMID- 26838548 TI - ABL kinases promote breast cancer osteolytic metastasis by modulating tumor-bone interactions through TAZ and STAT5 signaling. AB - Bone metastases occur in up to 70% of advanced breast cancer. For most patients with breast cancer, bone metastases are predominantly osteolytic. Interactions between tumor cells and stromal cells in the bone microenvironment drive osteolytic bone metastasis, a process that requires the activation of osteoclasts, cells that break down bone. We report that ABL kinases promoted metastasis of breast cancer cells to bone by regulating the crosstalk between tumor cells and the bone microenvironment. ABL kinases protected tumor cells from apoptosis induced by TRAIL (TNF-related apoptosis-inducing ligand), activated the transcription factor STAT5, and promoted osteolysis through the STAT5-dependent expression of genes encoding the osteoclast-activating factors interleukin-6 (IL 6) and matrix metalloproteinase 1 (MMP1). Furthermore, in breast cancer cells, ABL kinases increased the abundance of the Hippo pathway mediator TAZ and the expression of TAZ-dependent target genes that promote bone metastasis. Knockdown of ABL kinases or treatment with ABL-specific allosteric inhibitor impaired osteolytic metastasis of breast cancer cells in mice. These findings revealed a role for ABL kinases in regulating tumor-bone interactions and provide a rationale for using ABL-specific inhibitors to limit breast cancer metastasis to bone. PMID- 26838551 TI - Compatible Mechanism for a Simultaneous Description of the Roebuck, Dushman, and Iodate-Arsenous Acid Reactions in an Acidic Medium. AB - The iodine-arsenous acid (Roebuck), iodide-iodate (Dushman), and iodate-arsenous acid reactions have been studied simultaneously by a stopped-flow technique by monitoring the absorbance-time profiles at the isosbestic point of the I2/I3(-) system (468 nm). Using the well-accepted rate coefficients of iodine hydrolysis, we have proven that iodine is the kinetically active species of the iodine arsenous acid reaction. Strong iodide inhibition of this system is explained by a rapidly established equilibrium between iodine and arsenous acid to produce an iodide ion, a hydrogen ion, and a short-lived intermediate H2AsO3I, which is shifted far to the left. Taking into consideration the generally accepted kinetic model of the Dushman reaction where I2O2 plays a key role to account for all of the most important observations in this subsystem and a sequence of simple formal oxygen-transfer reactions between arsenous acid and iodic acid as well as iodous acid and hypoiodous acid, we propose a 13-step comprehensive kinetic model, including seven rapidly established equilibria with only six fitted parameters, that is able to explain all of the most important characteristics of the kinetic curves of all of the title systems both individually and simultaneously. PMID- 26838550 TI - The adhesion GPCR BAI1 mediates macrophage ROS production and microbicidal activity against Gram-negative bacteria. AB - The detection of microbes and initiation of an innate immune response occur through pattern recognition receptors (PRRs), which are critical for the production of inflammatory cytokines and activation of the cellular microbicidal machinery. In particular, the production of reactive oxygen species (ROS) by the NADPH oxidase complex is a critical component of the macrophage bactericidal machinery. We previously characterized brain-specific angiogenesis inhibitor 1 (BAI1), a member of the adhesion family of G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs), as a PRR that mediates the selective phagocytic uptake of Gram-negative bacteria by macrophages. We showed that BAI1 promoted phagosomal ROS production through activation of the Rho family guanosine triphosphatase (GTPase) Rac1, thereby stimulating NADPH oxidase activity. Primary BAI1-deficient macrophages exhibited attenuated Rac GTPase activity and reduced ROS production in response to several Gram-negative bacteria, resulting in impaired microbicidal activity. Furthermore, in a peritoneal infection model, BAI1-deficient mice exhibited increased susceptibility to death by bacterial challenge because of impaired bacterial clearance. Together, these findings suggest that BAI1 mediates the clearance of Gram-negative bacteria by stimulating both phagocytosis and NADPH oxidase activation, thereby coupling bacterial detection to the cellular microbicidal machinery. PMID- 26838553 TI - A case of type 1 diabetes mellitus with which localized insulin allergy was markedly alleviated by switching to insulin glulisine. PMID- 26838554 TI - Normative ADHD-RS-Preschool Data in a Community Sample in Spain. AB - OBJECTIVE: The objective was to obtain normalized data from the ADHD Rating Scale IV-Preschool Version (ADHD-RS-IV-P) in a Spanish sample. METHOD: We translated and adapted the ADHD-RS-IV to our culture to obtain normalized data from a random representative sample of 1,426 Spanish preschool children (3 to <7 years old; 49.7% males). To analyze differences between evaluators, we used MANOVA. Internal consistency was assessed via Cronbach's alpha. RESULTS: The mean age was 4.7 years old. There was a significant sex effect. The questionnaire had an internal consistency between .86 and .96 according to subscale and evaluator. CONCLUSION: To evaluate ADHD in preschool children, it is necessary to use scores standardized by sex. Using a validated scale in schools and primary care centers may be useful for early detection of ADHD. PMID- 26838552 TI - Notch-regulated miR-223 targets the aryl hydrocarbon receptor pathway and increases cytokine production in macrophages from rheumatoid arthritis patients. AB - Evidence links aryl hydrocarbon receptor (AHR) activation to rheumatoid arthritis (RA) pathogenesis, although results are inconsistent. AHR agonists inhibit pro inflammatory cytokine expression in macrophages, pivotal cells in RA aetiopathogenesis, which hints at specific circuits that regulate the AHR pathway in RA macrophages. We compared microRNA (miR) expression in CD14(+) cells from patients with active RA or with osteoarthritis (OA). Seven miR were downregulated and one (miR-223) upregulated in RA compared to OA cells. miR-223 upregulation correlated with reduced Notch3 and Notch effector expression in RA patients. Overexpression of the Notch-induced repressor HEY-1 and co-culture of healthy donor monocytes with Notch ligand-expressing cells showed direct Notch-mediated downregulation of miR-223. Bioinformatics predicted the AHR regulator ARNT (AHR nuclear translocator) as a miR-223 target. Pre-miR-223 overexpression silenced ARNT 3'UTR-driven reporter expression, reduced ARNT (but not AHR) protein levels and prevented AHR/ARNT-mediated inhibition of pro-inflammatory cytokine expression. miR-223 counteracted AHR/ARNT-induced Notch3 upregulation in monocytes. Levels of ARNT and of CYP1B1, an AHR/ARNT signalling effector, were reduced in RA compared to OA synovial tissue, which correlated with miR-223 levels. Our results associate Notch signalling to miR-223 downregulation in RA macrophages, and identify miR-223 as a negative regulator of the AHR/ARNT pathway through ARNT targeting. PMID- 26838555 TI - The Effectiveness of Mindfulness-Based Therapies for ADHD: A Meta-Analytic Review. AB - OBJECTIVE: Mindfulness-based therapies (MBTs) have been shown to be efficacious in treating internally focused psychological disorders (e.g., depression); however, it is still unclear whether MBTs provide improved functioning and symptom relief for individuals with externalizing disorders, including ADHD. To clarify the literature on the effectiveness of MBTs in treating ADHD and to guide future research, an effect-size analysis was conducted. METHOD: A systematic review of studies published in PsycINFO, PubMed, and Google Scholar was completed from the earliest available date until December 2014. RESULTS: A total of 10 studies were included in the analysis of inattention and the overall effect size was d = -.66. A total of nine studies were included in the analysis of hyperactivity/impulsivity and the overall effect was calculated at d = -.53. CONCLUSION: Results of this study highlight the possible benefits of MBTs in reducing symptoms of ADHD. PMID- 26838556 TI - Evaluating the Psychometric Properties of the Conners Adult ADHD Rating Scales. AB - OBJECTIVE: Characterized by significant work-related impairments, difficulties with relationships, and higher rates of criminal behavior and substance abuse, ADHD is now understood as a disability that can persist throughout a lifetime. Differing opinions remain, however, regarding adult symptoms of ADHD, particularly with regard to gender differences. These issues add to the challenges of constructing a reliable and valid measure of ADHD for use with adults in research and practice. METHOD: We review the theoretical foundations of ADHD and psychometric properties of a major assessment device, the Conners' Adult ADHD Rating Scales (CAARS). RESULTS: Results of the literature review found (a) a wide range of internal consistency estimates, with lowest values for the Diagnostic and Statistical Manual of Mental Disorders (DSM)-Hyperactive/Impulsive Symptoms subscale when completed by women, and (b) discriminant validity estimates in the same range as convergent validity estimates. CONCLUSION: These findings raise questions about the construct validity of the CAARS and suggest directions for future research. PMID- 26838557 TI - A Randomized Controlled Trial Evaluating the Efficacy of a Psychoeducation Program for Families of Children and Adolescents With ADHD in the United Kingdom: Results After a 6-Month Follow-Up. AB - OBJECTIVE: Psychoeducation forms part of the current practice for ADHD; however, its efficacy is yet to be established. METHOD: Sixty-nine children/adolescents with ADHD were randomly assigned for their families to receive either a well structured psychoeducation program (n = 35), or belong to a control group (treatment-as-usual, n = 34). RESULTS: One-way analyses of variance showed a statistically significant Treatment * Time interaction, for ADHD total symptoms, inattention/cognition, and hyperactivity/impulsivity subdomains according to the parents, the first two with medium-large effect sizes. The effects of the intervention on the ADHD total and the inattention/cognition domain persisted after 6 months follow-up. No significant differences in teacher ratings were found; however, an improvement in clinical functioning as measured by clinicians was observed. CONCLUSION: This psychoeducation program has shown effectiveness in reducing ADHD symptoms when compared with treatment as usual. Psychoeducation needs to be considered as a valid and additional approach in ADHD. PMID- 26838558 TI - Comorbidity of Adult ADHD and Its Subtypes With Substance Use Disorder in a Large Population-Based Epidemiological Study. AB - OBJECTIVE: The objective of the study is to explore the role and possible substance preference in ADHD and subtypes in substance use disorder (SUD). METHOD: Using self-report data on ADHD Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) symptoms and SUD (alcohol, illicit drugs, and nicotine) in 18,167 Swedish twins, aged 20 to 45 years, we obtained odds ratios (OR) from mixed effect logistic regression, controlling for age, sex, education, and nonindependence of twin data. RESULTS: Increased ADHD symptoms were significantly associated with increased odds for all SUD. ORs ranged between 1.33 for regular nicotine (95% confidence interval [CI] = [1.12, 1.59]); 2.54 for multiple drug use (95% CI = [2.00, 3.23]), and 3.58 for alcohol dependence (95% CI = [2.86, 4.49]). CONCLUSION: ADHD symptoms and subtypes in the population are associated with increased risks for all SUD outcomes, with no difference between ADHD subtypes, no substance preference, and no sex differences for the comorbidity. Clinicians need to consider ADHD evaluation and treatment as part of management of SUD in adults. PMID- 26838559 TI - From painstaking work to a new way of meeting the world-Trauma clients' experiences with skill training in a stabilization group approach. AB - OBJECTIVE: The study explored how former trauma clients experienced the inclusion of skill training in their treatment, their ways of relating to and using these skills, and how this changed over time. METHOD: Semi-structured qualitative in depth interviews were conducted with 13 clients within three months of their completion of treatment, and again 11-13 months later. RESULTS: Analysis of the material resulted in three main themes: (1) Being ready to find new ways to deal with trauma-related problems as a motivational starting point at intake, (2) Finding new agency through skills and understanding, and (3) One year on-Meeting the everyday world in a new way. An overreaching theme was the significant effort clients put into their treatments. CONCLUSIONS: The results show how skills over time became integrated and were linked to profound changes, including changes in emotional processing and an increased sense of agency. An experiential interrelationship between understanding and action was found, that supports the practice of coupling skill training with psychoeducation in trauma-specific treatment. PMID- 26838560 TI - Globalization of the Korean Journal of Medical Education. PMID- 26838561 TI - A new era of the Korean Journal of Medical Education: reborn as an international journal. PMID- 26838562 TI - Introducing a legal mandate for basic medical education accreditation in Korea. PMID- 26838563 TI - Students' perceptions and satisfaction level of hybrid problem-based learning for 16 years in Kyungpook National University School of Medicine, Korea. AB - PURPOSE: Kyungpook National University School of Medicine has been implementing hybrid problem-based learning (PBL) since 1999. The aim of this study was to investigate the changes in the students' perceptions and satisfaction levels of hybrid PBL. METHODS: The target period of our study was from 1999 to 2014, and target subjects were second-year medical students in Kyungpook National University School of Medicine. The survey was conducted at the end of semester. We had a focused interview with group leaders and some volunteer students. RESULTS: As for the scores regarding students' overall satisfaction with PBL, there was significant improvement in 2005 compared to 2002, but the scores decreased and no differences between the survey years noted after 2005. The students' preference ratio for the once a week PBL sessions, tutor presence, synchronization of contents, and arrangement of PBL sessions and related lectures was 60%-80%, 50%-90%, 52%-96%, and 78%-93%, respectively. CONCLUSION: In order to increase students' satisfaction with hybrid PBL and to improve the perception of it, firstly, it is necessary to arrange the date and the time of PBL sessions so that students can concentrate on PBL. Secondly, PBL cases should be selected and arranged to be well synchronized with the ongoing lectures. Finally, it is important to create a safe atmosphere so that students can engage actively in PBL sessions. PMID- 26838564 TI - Comparative study of goal contents and goal characteristics between medical and business students. AB - PURPOSE: Medical and business are one of the most popular majors among students, and both fields require intensive training to reach certain level of expertise. During the development of professionalism, goal can become a crucial role in psychological impetus. The purpose of this study is to compare goal contents, goal characteristics, and effect of goal characteristics on student's major satisfaction between medical and business. METHODS: A total of 193 undergraduate students (97 medical students, 96 business students) answered survey questions including goal contents, goal characteristics (goal autonomy, goal attainability, social value of goal) and satisfaction on their majors. Qualitative analysis of goal contents and quantitative analysis of goal characteristics, and their effects on student major satisfaction were performed. RESULTS: Goal content analysis showed percentage of social concern goal was higher in medical students (25.8%) than business students (6.3%), whereas percentage of wealth goal was higher business students (24.0%) than medical students (3.1%). Among goal characteristics, goal attainability and social value of goal were higher in medical students than business students. In both groups, social value of goal was significantly predict major satisfaction. CONCLUSION: Goal contents and goal characteristics are different between medical and business students. Curriculum and educational interventions that concerning students' goal and developing programs to enhance students' social value of goal is necessary. PMID- 26838565 TI - Longitudinal analysis of the effect of academic failure tolerance on academic achievement fluctuation in medical school students. AB - PURPOSE: Academic failure tolerance (AFT) is one of the important psychological concepts in education, but its applications in medical education are rare. Thus, the purpose of this study was to investigate the effect of academic failure tolerance on academic achievement fluctuation among medical school students using a longitudinal research design. METHODS: The subjects were 43 medical students who responded to the AFT test. This study analyzed the longitudinal data of achievement scores up to the 2nd academic year (2012-2013) among students who were divided into academic achievement improvement and decline groups. RESULTS: Comparing the improvement and decline groups' mean academic achievement fluctuation scores demonstrated that behavior and preferred task difficulty showed high scores whereas feeling scores were lower in the improvement group (p<0.05). CONCLUSION: In the improvement group, despite the higher negative feeling scores during academic failure, the students favored the more difficult subjects and were more assiduous in their studies. This will form an important basis for enhancing academic achievement among medical students. PMID- 26838566 TI - The relationship between medical students' epistemological beliefs and achievement on a clinical performance examination. AB - PURPOSE: This study was to explore the relationship between clinical performance examination (CPX) achievement and epistemological beliefs to investigate the potentials of epistemological beliefs in ill-structured medical problem solving tasks. METHODS: We administered the epistemological beliefs questionnaire (EBQ) to fourth-year medical students and correlated the results with their CPX scores. The EBQ comprised 61 items reflecting five belief systems: certainty of knowledge, source of knowledge, rigidity of learning, ability to learn, and speed of knowledge acquisition. The CPX included scores for history taking, physical examination, and patient-physician interaction. RESULTS: The higher epistemological beliefs group obtained significantly higher scores on the CPX with regard to history taking and patient-physician interaction. The epistemological beliefs scores on certainty of knowledge and source of knowledge were significantly positively correlated with patient-physician interaction. The epistemological beliefs scores for ability to learn were significantly positively correlated with those for history taking, physical examination, and patient physician interaction. CONCLUSION: Students with more sophisticated and advanced epistemological beliefs stances used more comprehensive and varied approaches in the patient-physician interaction. Therefore, educational efforts that encourage discussions pertaining to epistemological views should be considered to improve clinical reasoning and problem-solving competence in the clinic setting. PMID- 26838567 TI - Assessing clinical reasoning abilities of medical students using clinical performance examination. AB - PURPOSE: The purpose of this study is to investigate the reliability and validity of new clinical performance examination (CPX) for assessing clinical reasoning skills and evaluating clinical reasoning ability of the students. METHODS: Third year medical school students (n=313) in Busan-Gyeongnam consortium in 2014 were included in the study. One of 12 stations was developed to assess clinical reasoning abilities. The scenario and checklists of the station were revised by six experts. Chief complaint of the case was rhinorrhea, accompanied by fever, headache, and vomiting. Checklists focused on identifying of the main problem and systematic approach to the problem. Students interviewed the patient and recorded subjective and objective findings, assessments, plans (SOAP) note for 15 minutes. Two professors assessed students simultaneously. We performed statistical analysis on their scores and survey. RESULTS: The Cronbach alpha of subject station was 0.878 and Cohen kappa coefficient between graders was 0.785. Students agreed on CPX as an adequate tool to evaluate students' performance, but some graders argued that the CPX failed to secure its validity due to their lack of understanding the case. One hundred eight students (34.5%) identified essential problem early and only 58 (18.5%) performed systematic history taking and physical examination. One hundred seventy-three of them (55.3%) communicated correct diagnosis with the patient. Most of them had trouble in writing SOAP notes. CONCLUSION: To gain reliability and validity, interrater agreement should be secured. Students' clinical reasoning skills were not enough. Students need to be trained on problem identification, reasoning skills and accurate record keeping. PMID- 26838568 TI - The relationship among self-efficacy, perfectionism and academic burnout in medical school students. AB - PURPOSE: The purpose of this study was to examine the relationship among academic self-efficacy, socially-prescribed perfectionism, and academic burnout in medical school students and to determine whether academic self-efficacy had a mediating role in the relationship between perfectionism and academic burnout. METHODS: A total of 244 first-year and second-year premed medical students and first- to fourth-year medical students were enrolled in this study. As study tools, socially-prescribed perfectionism, academic self-efficacy, and academic burnout scales were utilized. For data analysis, correlation analysis, multiple regression analysis, and hierarchical multiple regression analyses were conducted. RESULTS: Academic burnout had correlation with socially-prescribed perfectionism. It had negative correlation with academic self-efficacy. Socially prescribed perfectionism and academic self-efficacy had 54% explanatory power for academic burnout. When socially-prescribed perfectionism and academic self efficacy were simultaneously used as input, academic self-efficacy partially mediated the relationship between socially-prescribed perfectionism and academic burnout. CONCLUSION: Socially-prescribed perfectionism had a negative effect on academic self-efficacy, ultimately triggering academic burnout. This suggests that it is important to have educational and counseling interventions to improve academic self-efficacy by relieving academic burnout of medical school students. PMID- 26838569 TI - Ubiquitous testing using tablets: its impact on medical student perceptions of and engagement in learning. AB - PURPOSE: Ubiquitous testing has the potential to affect medical education by enhancing the authenticity of the assessment using multimedia items. This study explored medical students' experience with ubiquitous testing and its impact on student learning. METHODS: A cohort (n=48) of third-year students at a medical school in South Korea participated in this study. The students were divided into two groups and were given different versions of 10 content-matched items: one in text version (the text group) and the other in multimedia version (the multimedia group). Multimedia items were delivered using tablets. Item response analyses were performed to compare item characteristics between the two versions. Additionally, focus group interviews were held to investigate the students' experiences of ubiquitous testing. RESULTS: The mean test score was significantly higher in the text group. Item difficulty and discrimination did not differ between text and multimedia items. The participants generally showed positive responses on ubiquitous testing. Still, they felt that the lectures that they had taken in preclinical years did not prepare them enough for this type of assessment and clinical encounters during clerkships were more helpful. To be better prepared, the participants felt that they needed to engage more actively in learning in clinical clerkships and have more access to multimedia learning resources. CONCLUSION: Ubiquitous testing can positively affect student learning by reinforcing the importance of being able to understand and apply knowledge in clinical contexts, which drives students to engage more actively in learning in clinical settings. PMID- 26838570 TI - Complex and novel determinants of empathy change in medical students. AB - PURPOSE: Physician empathy is a core attribute in medical professionals, giving better patient outcomes. Medical school is an opportune time for building empathetic foundations. This study explores empathy change and focuses on contributory factors. METHODS: We conducted a cross-sectional study involving 881 students (63%) from Years 1 to 5 in a Singaporean medical school using the Jefferson Scale of Physician Empathy-Student version (JSPE-S) and a questionnaire investigating the relationship between reported and novel personal-social empathy determinants. RESULTS: Empathy declined significantly between preclinical and clinical years. Female and medical specialty interest respondents had higher scores than their counterparts. Despite strong internal consistency, factor analysis suggested that the JSPE model is not a perfect fit. Year 1 students had highest Perspective Taking scores and Year 2 students had highest Compassionate Care scores. High workload and inappropriate learning environments were the most relevant stressors. Time spent with family, arts, and community service correlated with higher empathy scores, whilst time spent with significant others and individual leisure correlated with lower scores. Thematic analysis revealed that the most common self-reported determinants were exposure to activity (community service) or socialisation, personal and family-related event as well as environment (high work-load). CONCLUSION: While the empathy construct in multicultural Singapore is congruent with a Western model, important differences remain. A more subtle understanding of the heterogeneity of the medical student experience is important. A greater breadth of determinants of empathy, such as engagement in arts-related activities should be considered. PMID- 26838571 TI - Nurses versus physicians' knowledge, attitude, and performance on care for the family members of dying patients. AB - PURPOSE: Nurses and physicians must be competent enough to provide care for the clients. As a lack of knowledge and a poor attitude result in a low performance of delivering care, this study aimed to explore the nurses versus physicians' knowledge, attitude, and performance on care for the family members of dying patients (FMDPs). METHODS: This descriptive study was conducted at the educational hospitals in Isfahan, Iran. The samples were 110 nurses and 110 physicians. The data were collected through a convenience sampling method and using a valid and reliable questionnaire. RESULTS: The average knowledge, attitude, and performance on care for the FMDPs were not significantly different between nurses and physicians (p>0.05). The majority of nurses (55.4%) and physician (63.6%) were at a moderate and a fair level of knowledge of care for the FMDPs. Most of the nurses (81%) and physicians (87.3%) had a positive attitude towards caring the FMDPs. Most of the nurses (70%) and physicians (86.3%) had a moderate and fair performance. CONCLUSION: Having enough knowledge and skills, and a positive attitude are necessary for caring the FMDPs. Nurses' and physicians' competencies must be improved through continuing educational programs and holding international and national conferences with a focus on the palliative care. PMID- 26838572 TI - Improvement of debate competence: an outcome of an introductory course for medical humanities. AB - PURPOSE: Academic debate is an effective method to enhance the competences of critical thinking, problem solving, communication skills and cooperation skills. The present study examined the improvement of debate competence which is an outcome of debate-based flipped learning. METHODS: A questionnaire was administrated to second-year premedical school students at Yeungnam University. In total 45 students participated in the survey. The survey questionnaire was composed of 60 items of eight subfactors on debate competence. To investigate the homogeneous of low and high achievement groups, 18 items on empathy and 75 items on critical thinking scales were used. To compare the pretest with posttest scores, data was analyzed using paired sample t-test. RESULTS: There were no significant differences between low and high achievement groups by average grade at the beginning of the semester. There was a significant improvement in high achievers on the logical argumentation (p<0.001), proficiency in inquiry (p<0.01), active participation (p<0.001), ability to investigate and analyze (p<0.001), observance of debate rules (p<0.05), and acceptability (p<0.05). Even in low achievers, active participation (p<0.05) and ability to investigate and analyze (p<0.01) were significantly improved. CONCLUSION: Results showed that students could improve their debate competence by the debate-based flipped learning. A prospective and comparative study on the communication and teamwork competences needs to be conducted in the future. It is suggested that in-depth discussion for the curriculum design and teaching will be needed in terms of the effectiveness and the outcomes of the medical humanities. PMID- 26838573 TI - Specialty choice preference of medical students according to personality traits by Five-Factor Model. AB - PURPOSE: The purpose of this study was to determine the relationship between personality traits, using the Five-Factor Model, and characteristics and motivational factors affecting specialty choice in Korean medical students. METHODS: A questionnaire survey of Year 4 medical students (n=110) in July 2015 was administered. We evaluated the personality traits of Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness by using the Korean version of Big Five Inventory. Questions about general characteristics, medical specialties most preferred as a career, motivational factors in determining specialty choice were included. Data between five personality traits and general characteristics and motivational factors affecting specialty choice were analyzed using Student t-test, Mann-Whitney test and analysis of variance. RESULTS: Of the 110 eligible medical students, 105 (95.4% response rate) completed the questionnaire. More Agreeableness students preferred clinical medicine to basic medicine (p=0.010) and more Openness students preferred medical departments to others (p=0.031). Personal interest was the significant motivational factors in more Openness students (p=0.003) and Conscientiousness students (p=0.003). CONCLUSION: Medical students with more Agreeableness were more likely to prefer clinical medicine and those with more Openness preferred medical departments. Personal interest was a significant influential factor determining specialty choice in more Openness and Conscientiousness students. These findings may be helpful to medical educators or career counselors in the specialty choice process. PMID- 26838574 TI - What is like to be a devoted doctor? An analysis of book reports on The Painted Veil. AB - PURPOSE: The aim of this study is to see what medical students think about the role of spouse of a devoted medical doctor through the book reports of The Painted Veil (1925). METHODS: The 53 medical students were asked to read Maugham's The Painted Veil and to have a discussion. In their book reports, following questions were asked to be included: What it is like to be married a devoted medical doctor? Do you think that patients realize, value, and respect the importance of doctor's work? In the outbreak of highly infectious and fatal disease, can you carry out a heroic fight to control it? RESULTS: Among the 53 respondents, seven students (13%) answered that they would be happy if they marry a devoted doctor and scientist and 34 (64%) unhappy. The remaining 12 (23%) could not make a decision. The six students (11%) answered that doctor is valued and respected by patients while 46 (87%) answered doctor is neither valued nor respected. The remaining one (2%) could not decide. The 20 students (38%) answered that they would fight for the infectious disease and the remaining 30 (57%) answered that they would not. The remaining three (5%) could not determine their mind. CONCLUSION: The Painted Veil induced a virtue of "life of balance and harmony" and "attitude of doctor who give superiority to responsibility and duty over prestige and wealth" from the medical students. It could be a good teaching material for medical humanity. PMID- 26838575 TI - Importance of language skill learning of dental undergraduates: need assessment and remediation in India. AB - For students entering health education, it is essential to learn the languages that are native to the place of education. The study is undertaken with purpose to assess language skill of undergraduate students at Sharad Pawar Dental College in India so that remedying can be planned at their entry to the new course. This cross-sectional study was done from September 2014 to February 2015. The 157 dental undergraduates were subjected to structured questionnaire that has items on their assessment of three languages i.e., Marathi, Hindi and English. Later, the need assessment to develop language skills of students was done through focus group discussions. Students' perception about language classes was obtained through interviews. The correct response rate of study participants to test items on three languages ranged from 69.4%-81.05% and 82.5%-91.59% for first and second year, respectively. There were significant differences in response rate among three language item groups. The language classes brought out appreciable changes in their understanding of local languages. Study brought out need to address language gaps to aid to smooth out their transitions in new institute. PMID- 26838576 TI - Evaluation of a personal and professional development module in an undergraduate medical curriculum in India. AB - The study aimed at evaluating the personal and professional development (PPD) module in the undergraduate medical curriculum in Melaka Manipal Medical College, India. PPD hours were incorporated in the curriculum. A team of faculty members and a faculty coordinator identified relevant topics and students were introduced to topics such as medical humanities, leadership skills, communication skills, ethics, professional behavior, and patient narratives. The module was evaluated using a prevalidated course feedback questionnaire which was administered to three consecutive batches of students from March 2011 to March 2013. To analyze faculty perspectives, one to one in-depth interviews and focus group discussions were conducted by the coordinators with faculty members who conducted the PPD classes. Analysis of the course feedback form revealed that majority (80%) of students agreed that the module was well prepared and was "highly relevant" to the profession. Faculty found the topics new and interdisciplinary and there was a sense of sharing responsibility and workload by the faculty. PPD modules are necessary components of the curriculum and help to mould students while they are still acquiescent as they assume their roles as doctors of the future. PMID- 26838577 TI - Increased correlation coefficient between the written test score and tutors' performance test scores after training of tutors for assessment of medical students during problem-based learning course in Malaysia. AB - This paper is aimed at finding if there was a change of correlation between the written test score and tutors' performance test scores in the assessment of medical students during a problem-based learning (PBL) course in Malaysia. This is a cross-sectional observational study, conducted among 264 medical students in two groups from November 2010 to November 2012. The first group's tutors did not receive tutor training; while the second group's tutors were trained in the PBL process. Each group was divided into high, middle and low achievers based on their end-of-semester exam scores. PBL scores were taken which included written test scores and tutors' performance test scores. Pearson correlation coefficient was calculated between the two kinds of scores in each group. The correlation coefficient between the written scores and tutors' scores in group 1 was 0.099 (p<0.001) and for group 2 was 0.305 (p<0.001). The higher correlation coefficient in the group where tutors received the PBL training reinforces the importance of tutor training before their participation in the PBL course. PMID- 26838578 TI - The Mi1000 CONCERTO PIN cochlear implant: An evaluation of its safety and stability in adults and children. AB - Conclusion The study demonstrates the medium-term stability and safety of the CONCERTO PIN cochlear implant. The use of the CONCERTO PIN proved to be suitable for the use of a surgical technique without the need for suture fixation and resulted in short surgery duration and a low medium-term complication rate. Objective The primary aim was to provide data on medium-term safety and stability of the CONCERTO PIN cochlear implant in adults and children, and to collect feedback on the surgical technique used, which involved no drilling and no suture fixation. The secondary aim was to analyze surgery duration. Methods Implantation was performed using minimally invasive surgery. During surgery, data on the surgical procedure was collected by the attending surgeons or a designee. Safety and stability of the CONCERTO PIN were assessed at first fitting (1 month after implantation) and 6 months after first fitting. Results Ninety-nine patients were implanted with a CONCERTO PIN implant and one patient with a CONCERTO implant. The CONCERTO PIN implants implanted during this study were immobilized by pins and a tight periosteal pocket. The mean (+/- SD) surgery duration was 27:52 (+/- 9:19) min. PMID- 26838579 TI - New scoring system of an interview for the diagnosis of benign paroxysmal positional vertigo. AB - Conclusion This study investigated a novel instrument to diagnose benign paroxysmal positional vertigo (BPPV). Objective To develop a new scoring system of an interview for the diagnosis of BPPV. Methods The answers to questions on dizziness and/or vertigo (D/V) (571 patients) were analyzed and the questions for which the answers differed significantly between the patients with and without BPPV were selected. Results This study established an intensive questionnaire with a scoring system. It consists of the following questions: (1) Is rotary vertigo a characteristic of your D/V? (2) Is your D/V triggered when you roll your head over in a supine position? (3) Does your D/V disappear within 5 min? (4) Have you previously experienced hearing loss in one ear, or have you experienced hearing loss, tinnitus, or ear fullness with this D/V? One point each was given to an answer of 'yes' to questions (1) and (2). Two points were given to an answer of 'yes' to question (3). One point was subtracted upon an answer of 'yes' to question (4). When the total score was greater than two points, the patient was diagnosed with BPPV. The sensitivity of the diagnosis of BPPV by this scoring system was 81% and the specificity was 69%. PMID- 26838580 TI - Aspiration as a late complication after accelerated versus conventional radiotherapy in patients with head and neck cancer. AB - Conclusion Neck dissection after radiotherapy increased the risk of aspiration as a late effect in a sub-sample of patients treated for head and neck cancer in the ARTSCAN study. Patients treated with accelerated fractionation (AF) developed aspiration, with or without coughing, more frequently than patients treated with conventional fractionation (CF). Objectives A long-term follow-up study was conducted to determine the frequency of aspiration as a late effect in patients with head and neck cancer treated with AF or CF. Method One-hundred and eight patients were recruited from two centres of the Swedish multi-centre study, ARTSCAN, where AF and CF were compared. Patients with positive lymph nodes were treated with neck dissection after completing radiotherapy. The follow-up was performed at a median of 65 months after initiation of radiotherapy and included an ENT and a videofluoroscopic examination. Results Aspiration was found in 51/108 (47%) and silent aspiration in 34/96 (35%) patients. Neck dissection (n = 47 patients) was significantly associated with both aspiration and silent aspiration. Aspiration was more common among patients treated with AF (34/61; 56%) compared to CF (17/47; 36%; p = 0.053). Silent aspiration was also more common after AF (24/54; 44%) than after CF (10/42; 24%; p = 0.052). PMID- 26838581 TI - Rate of recurrence and malignant transformation in 88 cases with inverted papilloma between 1998-2008. AB - Conclusions The recurrence rate of IP in the current study is comparable to international and national studies. When the primary tumour was located in the frontal or the sphenoid sinus, the tumour seemed more likely to recur. Some recurrences were more than 2 years after primary surgery, suggesting continued need for long-term follow-up. The rate of malignant transformation in inverted papilloma cases has not changed in Denmark. Objectives Inverted papillomas are benign tumours located in the nasal cavity and paranasal sinuses. They are known for their tendency to recur after surgery and show invasive growth, causing bone remodulation and the association with malignant transformation. The introduction of endoscopic sinus surgery and computer aided sinus surgery over the last decades has made this tumour more approachable with less cosmetic and functional damage. The objective of this study is to establish whether the recurrence rate and the rate of malignant transformation of IP have changed with the application of these new techniques. Method A retrospective study between 1998-2008 including 88 cases with inverted papilloma. Results In total, 25.3% had recurrence. Combined surgical approach with endoscope/open approach had the lowest rate of recurrence. A malignant transformation in the postoperative histological examination was found in 8.9%. PMID- 26838583 TI - Daptomycin-Based 3 Week Treatment Scheme for the First Cellulitis Episode: Low Recurrence Rate Indicative of Decreased Recurrence Propensity? AB - INTRODUCTION: Cellulitis recurrences are frequent, difficult to manage, and contribute considerably to overall disease burden. This retrospective cases series reports recurrence rates of first community-acquired lower limb disease episode initially treated with daptomycin. METHODS: Treatment consisted of a 21 day two substances sequential scheme: intravenous daptomycin (4 mg/kg/day) during hospitalization and roxithromycin (2 * 150 mg per os) afterwards. Primary study end-point was the rate of recurrences during follow-up; recurrence rates and their binomial 95% confidence intervals (CI) were calculated with SPSS 22.0. Recurrences were identified by (1) review of hospital records and (2) telephone questionnaires. RESULTS: Twenty-seven patients hospitalized for first lower limb cellulitis episodes were started on daptomycin and 26 patients completed the above three-week sequential treatment scheme. During follow-up (range 37-85 months) one recurrence occurred among the 26 patients who completed the treatment: 96.2% of these patients remained relapse free at the end of follow-up (CI 79.5-99.9%). Considering also treatment failure, the overall effectiveness of this combination treatment was 92.6% recurrence free after more than 3 years follow-up (25/27 patients; CI 75.5-99.0%). This study is limited by retrospective planning and the restricted number of included patients. CONCLUSION: The choice of the treatment for the initial lower limb cellulitis episode may impact the risk of disease recurrences. Future studies should explore interventions for the first cellulitis episode as a means to modify the risk of the recurring course of this disease. PMID- 26838582 TI - Histological and Immunohistological Findings Using Anti-Cortisol Antibody in Atopic Dermatitis with Topical Steroid Addiction. AB - INTRODUCTION: Though topical steroid addiction (TSA) in patients with atopic dermatitis (AD) has been recently discussed as a clinical problem, there are very few studies about its mechanism. The purpose of this study was to elucidate histological and immunohistological characteristics of TSA using anti-cortisol antibody. METHODS: Skin biopsy specimen from eight patients with AD was stained by anti-cortisol antibody (Biorbyt, orb79379). Subjects consisted of a child patient with a short history of topical corticosteroids (TCS) application, an adult patient with a long history of TCS application, and six adult patients who have experienced topical steroid withdrawal (TSW) and the rebound phenomenon. RESULTS: The staining in the epidermis by anti-cortisol antibody presented patchy defects in the child patient, the patient with a long history of TCS application, and two patients at the rebound period. Parakeratosis with poor formation of corneal layer was obvious in the child patient, the patient with a long history of TCS application, two patients recovered from TSA, and two patients at the rebound period. CONCLUSION: Prolonged application of TCS might suppress the cortisol production of keratinocytes which is poorly developed at the early ages before childhood and completed naturally as to growth. Rebound phenomenon after TSW can occur due to the relative insufficiency of cortisol in the epidermis and the immature corneal layer formation. PMID- 26838584 TI - Reversible growth failure and complete GH deficiency in a 4-year-old girl with very early Hashimoto's thyroiditis and subsequent hyperplasia of pituitary thyrotroph cells. AB - Hashimoto's thyroiditis is a well-known cause of growth retardation in adolescence. It is less frequently seen in children and rarely seen in infants. A 4-year-old girl was referred to our clinic for a second opinion before starting growth hormone (GH) treatment. Linear growth had markedly declined in the past 2 years, with height -3.4 standard deviations. GH deficiency was complete. She had dry, gray-sallow skin and bloated abdomen, but no goiter. The parents reported fatigue and constipation. Hormonal evaluation revealed TSH 629.5 mIU/ml, free T4 0.08 ng/dl, and prolactin 17.2 ng/ml. Bone age was 2 years. Antibodies to thyroglobulin and thyroid peroxidase were positive, suggesting Hashimoto's thyroiditis. Brain magnetic resonance imaging showed anterior pituitary hyperplasia. After 3 years of L-thyroxine therapy, she was symptomless, her height was -0.6 standard deviations, and the TSH level was normal. Brain magnetic resonance imaging showed regression of the pituitary hyperplasia. CONCLUSIONS: This report describes a patient with Hashimoto's thyroiditis and pituitary hyperplasia, both quite rare in very young children. Acquired hypothyroidism may appear after neonatal screening and therefore should not be overlooked in investigations of short stature, even when clinical signs of hypothyroidism are absent. WHAT IS KNOWN: * Hashimoto's thyroiditis and pituitary hyperplasia are rare in very young children. * Acquired hypothyroidism can appear after negative neonatal screening and should not be overlooked. What is New: * Short children should be evaluated for growth hormone deficiency but only after excluding other causes, particularly hypothyroidism, as we report a child with this disease but no clinical signs of it. PMID- 26838586 TI - Can We Be Less Radical with Surgery for Early Cervical Cancer? AB - Although a rare cancer in the developed world due to the success of cervical screening programmes, cervical cancer remains one of the most common cancers diagnosed in women under the age of 35 years old. Radical hysterectomy and more recently radical trachelectomy have been highly effective in curing the majority of women with early stage disease. Many, however, are left with long-term 'survivorship' issues including bowel, bladder and sexual dysfunction. In view of these chronic co-morbidities, many clinicians now consider whether a less radical approach to surgery may be an option for some women. This review focuses on the current evidence for the safety of conservative surgery for early stage cervical cancer with regard to cure rates in comparison to standard management, as well as any improvement in short and long-term morbidity associated with a more conservative approach. PMID- 26838585 TI - Radiation Toxicity to the Cardiovascular System. AB - Radiation therapy is an important component of cancer treatment, and today, it is applied to approximately 50% of malignancies, including valvular, myocardial, pericardial, coronary or peripheral vascular disease, and arrhythmias. An increased clinical suspicion and knowledge of those mechanisms is important to initiate appropriate screening for the optimal diagnosis and treatment. As the number of cancer survivors has been steadily increasing over the last decades, cardio-oncology, an evolving subspecialty of cardiology, will soon play a pivotal role in raising awareness of the increased cardiovascular risk and formulate strategies to optimally manage patients in this unique population. PMID- 26838587 TI - Alberta Stroke Program Early CT Score applied to CT angiography source images is a strong predictor of futile recanalization in acute ischemic stroke. AB - INTRODUCTION: Reliable predictors of poor clinical outcome despite successful revascularization might help select patients with acute ischemic stroke for thrombectomy. We sought to determine whether baseline Alberta Stroke Program Early CT Score (ASPECTS) applied to CT angiography source images (CTA-SI) is useful in predicting futile recanalization. METHODS: Data are from the FUN-TPA study registry (ClinicalTrials.gov; NCT02164357) including patients with acute ischemic stroke due to proximal arterial occlusion in anterior circulation, undergoing reperfusion therapies. Baseline non-contrast CT and CTA-SI-ASPECTS, time-lapse to image acquisition, occurrence, and timing of recanalization were recorded. Outcome measures were NIHSS at 24 h, symptomatic intracranial hemorrhage, modified Rankin scale score, and mortality at 90 days. Futile recanalization was defined when successful recanalization was associated with poor functional outcome (death or disability). RESULTS: Included were 110 patients, baseline NIHSS 17 (IQR 12; 20), treated with intravenous thrombolysis (IVT; 45 %), primary mechanical thrombectomy (MT; 16 %), or combined IVT + MT (39 %). Recanalization rate was 71 %, median delay of 287 min (225; 357). Recanalization was futile in 28 % of cases. In an adjusted model, baseline CTA-SI ASPECTS was inversely related to the odds of futile recanalization (OR 0.5; 95 % CI 0.3-0.7), whereas NCCT-ASPECTS was not (OR 0.8; 95 % CI 0.5-1.2). A score <=5 in CTA-SI-ASPECTS was the best cut-off to predict futile recanalization (sensitivity 35 %; specificity 97 %; positive predictive value 86 %; negative predictive value 77 %). CONCLUSIONS: CTA-SI-ASPECTS strongly predicts futile recanalization and could be a valuable tool for treatment decisions regarding the indication of revascularization therapies. PMID- 26838589 TI - Asperger's Syndrome, Subjectivity and the Senses. AB - Situated at the intersection of anthropological work on illness narratives and research on the anthropology of autism, this paper is a close reading of an autobiographical narrative recounted by Peter, a young man diagnosed with Asperger's Syndrome, a type of autism spectrum disorder (ASD). Responding to Solomon's (2010a:252) call for phenomenologically grounded accounts of "the subjective, sensory, and perceptual experiences of autism ... based on personal narratives and practices of being and self-awareness," this paper calls into question key assumptions in the clinical and popular literature about ASD relating to theory of mind, empathy, capacity for metaphorical thinking, and ASD as a life-long condition. PMID- 26838588 TI - Skeletal muscle alkaline Pi pool is decreased in overweight-to-obese sedentary subjects and relates to mitochondrial capacity and phosphodiester content. AB - Defects in skeletal muscle energy metabolism are indicative of systemic disorders such as obesity or type 2 diabetes. Phosphorus magnetic resonance spectroscopy ((31)P-MRS), in particularly dynamic (31)P-MRS, provides a powerful tool for the non-invasive investigation of muscular oxidative metabolism. The increase in spectral and temporal resolution of (31)P-MRS at ultra high fields (i.e., 7T) uncovers new potential for previously implemented techniques, e.g., saturation transfer (ST) or highly resolved static spectra. In this study, we aimed to investigate the differences in muscle metabolism between overweight-to-obese sedentary (Ob/Sed) and lean active (L/Ac) individuals through dynamic, static, and ST (31)P-MRS at 7T. In addition, as the dynamic (31)P-MRS requires a complex setup and patient exercise, our aim was to identify an alternative technique that might provide a biomarker of oxidative metabolism. The Ob/Sed group exhibited lower mitochondrial capacity, and, in addition, static (31)P-MRS also revealed differences in the Pi-to-ATP exchange flux, the alkaline Pi-pool, and glycero phosphocholine concentrations between the groups. In addition to these differences, we have identified correlations between dynamically measured oxidative flux and static concentrations of the alkaline Pi-pool and glycero phosphocholine, suggesting the possibility of using high spectral resolution (31)P-MRS data, acquired at rest, as a marker of oxidative metabolism. PMID- 26838590 TI - Histologic outcome of thyroid nodules with repeated diagnosis of atypia in thyroid fine-needle aspiration biopsy. AB - AIM: We hypothesized that the estimated risk of malignancy for atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is higher than anticipated in Bethesda system. Therefore, we analyzed the actual malignancy risk of repeated AUS/FLUS diagnosis of thyroid fine-needle aspiration biopsies (FNAB). MATERIALS & METHODS: We reported retrospective analyzes of 112 cases with repeated AUS/FLUS diagnosis among 10,769 thyroid FNABs. The histologic follow-up were evaluated in the study. RESULTS: 112 cases with a repeated diagnosis of AUS/FLUS, histologic follow-up revealed 56 (50%) benign, 46 (41%) malignant and ten (9%) well-differentiated tumors of uncertain malignant potential outcome. CONCLUSION: The malignancy risk of AUS/FLUS category in thyroid FNABs was higher than anticipated in Bethesda system. Therefore, the management strategy of AUS/FLUS should be revised. PMID- 26838592 TI - Sports injury of the pediatric musculoskeletal system. AB - Sports related injuries are common in children and adolescents, with a reported incidence of around one in ten children each year. Boys incur more and severer sports injuries than girls, and chance for injury is greater with contact or jumping sports. Sports injuries seen in children under 10-years of age are non specific, including contusions, mild sprains, and extremity fractures, usually Salter fractures of the physes (growth plate) or plastic fractures. In the very young athlete, sports injury of the ligaments or muscle is rare as are spine or head injuries. With growth and adolescence, the intensity of sports involvement increases. Pre-pubertal children still have open physes that are prone to injury, both acute or due to stress from a repetitive activity. In addition to injury of the physes of the long bones, injuries to the physes of apophyses are common. Ligamentous injury is uncommon before physeal closure, but can occur. After the physes fuse, ligamentous injury is seen with patterns similar to adults. This review will include a description of sports related injuries seen in children and adolescents. We will concentrate on injuries that are specific for the growing skeleton, with a brief mention of those seen after fusion of the physes. PMID- 26838591 TI - Features and perspectives of MR enterography for pediatric Crohn disease assessment. AB - The aim of this paper is to provide indications for performing magnetic resonance enterography (MRE) in Crohn's disease (CD), the essential technical elements of MRE techniques and typical findings in patients with CD. Patients suffering from CD frequently require cross-sectional imaging. By performing MRE, it is possible to obtain results comparable to those obtained with endoscopy in terms of identifying and assessing disease activity and better than other cross-sectional imaging techniques, such as CT, in the evaluation of the fibrosis and complications of disease. The MR imaging of diffusion MR is a technique which enables medical staff to add important additional information and which may replace the use of intravenous contrast agents in the near future. Magnetic resonance enterography is an accurate tool for assessing bowel disease and the various complications associated with CD. The lack of exposure to non-ionizing radiation is an important advantage of this imaging technique, especially in the case of pediatric patients. Familiarity with common and pathognomonic imaging features of CD is essential for every clinician involved in the treatment of inflammatory bowel disease and the care of patients. PMID- 26838594 TI - [The Academy of Trauma Surgery (AUC). Service provider and management organization of the DGU]. AB - At the beginning of this century the German Trauma Society (DGU) became extensively active with an initiative on quality promotion, development of quality assurance and transparency regarding treatment of the severely injured. A white book on "Medical care of the severely injured" was published, focusing on the requirements on structural quality and especially procedural quality. The impact of the white book was immense and a trauma network with approved trauma centers, structured and graded for their individual trauma care performance, was developed. In order to monitor and document the required quality of care, a registry was needed. Furthermore, for cooperation within the trauma networks innovative methods for digital transfer of radiological images and patient documents became necessary. Finally, the auditing criteria for trauma centers had and still have to be completed with advanced medical education and training programs. In order to realize the implementation of such a broad spectrum of economically relevant and increasingly complex activities the Academy of Trauma Surgery (AUC) was established as a subsidiary of the DGU in 2004. The AUC currently has four divisions: 1) networks and health care structures, 2) registries and research management, 3) telemedicine, 4) medical education and training, all of which serve the goal of the initiative. The AUC is a full service provider and management organization in compliance with the statutes of the DGU. According to these statutes the business operations of the AUC also cover projects for numerous groups of patients, projects for the joint society the German Society for Orthopedics and Trauma (DGOU) as well as other medical institutions. This article describes the success stories of the trauma network (TraumaNetzwerk DGU(r)), the TraumaRegister DGU(r), the telecooperation platform TKmed(r), the new and fast-growing orthogeriatric center initiative (AltersTraumaZentrum DGU(r)) and the division of medical education and training, e.g. advanced trauma life support (ATLS(r)) and other training programs including the innovative interpersonal competence (IC) course. PMID- 26838593 TI - Comparison of the portion size and frequency of consumption of 156 foods across seven European countries: insights from the Food4ME study. AB - There are no standardised serving/portion sizes defined for foods consumed in the European Union (EU). Typical serving sizes can deviate significantly from the 100 g/100 ml labelling specification required by the EU legislation. Where the nutritional value of a portion is specified, the portion size is determined by the manufacturers. Our objective was to investigate the potential for standardising portion sizes for specific foods, thereby ensuring complementarity across countries. We compared portion size for 156 food items measured using a food frequency questionnaire across the seven countries participating in the Food4me study. The probability of consuming a food and the frequency of consumption differed across countries for 93% and 58% of the foods, respectively. However, the individual country mean portion size differed from the average across countries in only 16% of comparisons. Thus, although dietary choices vary markedly across countries, there is much less variation in portion sizes. Our results highlight the potential for standardisation of portion sizes on nutrition labels in the EU. PMID- 26838595 TI - [Tendoscopy of the Achilles tendon. Indications, technique and results]. AB - BACKGROUND: Endoscopic surgical techniques are nowadays standard procedures in medicine. The advantages of these minimally invasive techniques compared to open techniques are a smaller access route with reduced tissue damage, reduced scarring and often faster postoperative mobilization. Tendoscopy can be used to treat pathologies of tendons as well as of the surrounding tissues. OBJECTIVES: This article presents the advantages of endoscopic treatment of the Achilles tendon compared to open procedures as well as the chances and limitations of tendoscopy. MATERIAL AND METHODS: Surgical instructions for endoscopy of the Achilles tendon are presented and a review of the literature is given. RESULTS: The literature review showed excellent results for pathologies of the paratenon and Achilles tendinitis. Compared to open surgery there was a significantly lower rate of wound healing problems. All articles reported a high reduction of pain level with an early return to sports activities. Limitations of the procedure are extensive intratendinous pathologies and alterations of tendon insertion sites. CONCLUSION: Tendoscopy of the Achilles tendon is a safe but sometimes challenging minimally invasive technique for the treatment of paratendinopathy. PMID- 26838596 TI - Impacting clinical evaluation of anterior talofibular ligament injuries through analysis of ultrasound images. AB - BACKGROUND: Anterior talofibular ligament (ATFL) is considered as the weakest ankle ligament that is most prone to injuries. Ultrasound imaging with its portable, non-invasive and non-ionizing radiation nature is increasingly being used for ATFL diagnosis. However, diagnosis of ATFL injuries requires its segmentation from ultrasound images that is a challenging task due to the existence of homogeneous intensity regions, homogeneous textures and low contrast regions in ultrasound images. To address these issues, this research has developed an efficient ATFL segmentation framework that would contribute to accurate and efficient diagnosis of ATFL injuries for clinical evaluation. METHODS: The developed framework comprises of five computational steps to segment the ATFL ligament region. Initially, region of interest is selected from the original image, which is followed by the adaptive histogram equalization to enhance the contrast level of the ultrasound image. The enhanced contrast image is further optimized by the particle swarm optimization algorithm. Thereafter, the optimized image is processed by the Chan-Vese method to extract the ATFL region through curve evolution; then the resultant image smoothed by morphological operation. The algorithm is tested on 25 subjects' datasets and the corresponding performance metrics are evaluated to demonstrate its clinical applicability. RESULTS: The performance of the developed framework is evaluated based on various measurement metrics. It was found that estimated computational performance of the developed framework is 12 times faster than existing Chan-Vese method. Furthermore, the developed framework yielded the average sensitivity of 98.3 %, specificity of 96.6 % and accuracy of 96.8 % as compared to the manual segmentation. In addition, the obtained distance using Hausdorff is 14.2 pixels and similarity index by Jaccard is 91 %, which are indicating the enhanced performance whilst segmented area of ATFL region obtained from five normal (average Pixels-16,345.09), five tear (average Pixels-14,940.96) and five thickened (average Pixels-12,179.20) subjects' datasets show good performance of developed framework to be used in clinical practices. CONCLUSIONS: On the basis of obtained results, the developed framework is computationally more efficient and more accurate with lowest rate of coefficient of variation (less than 5 %) that indicates the highest clinical significance of this research in the assessment of ATFL injuries. PMID- 26838597 TI - Depressive Symptoms During Adolescence and Young Adulthood and the Development of Type 2 Diabetes Mellitus. AB - Although depression symptoms have been associated with type 2 diabetes mellitus (T2DM) among adults, little is known about the association of adolescent-onset depression and development of T2DM in young adulthood and whether the association differs by sex. We examined the association between high levels of depressive symptoms in adolescence and T2DM in adulthood in the National Longitudinal Study of Adolescent to Adult Health (n = 12,657). Adolescents completed the 20-item version of Center for Epidemiologic Studies Depression Scale during wave 1 (mean age, 16 years) and the 10-item version during follow-up (mean age, 29 years). A high level of depressive symptoms was defined as a score of 16 or higher on the 20-item version or 11 or higher on the 10-item version. T2DM was identified 13 years after baseline on the basis of either a glycated hemoglobin concentration of at least 6.5% or use of hypoglycemic medication (with or without insulin). Participants who reported taking insulin alone were classified as having type 1 diabetes mellitus and excluded. In models adjusted for demographic characteristics, women were at a higher risk of developing T2DM if they experienced high levels of depressive symptoms during both adolescence and adulthood (odds ratio = 1.96, 95% confidence interval: 1.23, 3.11) than were those who did not experience a high level of symptoms at either time point. No statistically significant associations were noted among men (odds ratio = 0.46, 95% confidence interval: 0.20, 1.05). PMID- 26838598 TI - HSP60 plays a regulatory role in IL-1beta-induced microglial inflammation via TLR4-p38 MAPK axis. AB - BACKGROUND: IL-1beta, also known as "the master regulator of inflammation", is a potent pro-inflammatory cytokine secreted by activated microglia in response to pathogenic invasions or neurodegeneration. It initiates a vicious cycle of inflammation and orchestrates various molecular mechanisms involved in neuroinflammation. The role of IL-1beta has been extensively studied in neurodegenerative disorders; however, molecular mechanisms underlying inflammation induced by IL-1beta are still poorly understood. The objective of our study is the comprehensive identification of molecular circuitry involved in IL-1beta-induced inflammation in microglia through protein profiling. METHODS: To achieve our aim, we performed the proteomic analysis of N9 microglial cells with and without IL-1beta treatment at different time points. Expression of HSP60 in response to IL-1beta administration was checked by quantitative real-time PCR, immunoblotting, and immunofluorescence. Interaction of HSP60 with TLR4 was determined by co-immunoprecipitation. Inhibition of TLR4 was done using TLR4 inhibitor to reveal its effect on IL-1beta-induced inflammation. Further, effect of HSP60 knockdown and overexpression were assessed on the inflammation in microglia. Specific MAPK inhibitors were used to reveal the downstream MAPK exclusively involved in HSP60-induced inflammation in microglia. RESULTS: Total 21 proteins were found to be differentially expressed in response to IL-1beta treatment in N9 microglial cells. In silico analysis of these proteins revealed unfolded protein response as one of the most significant molecular functions, and HSP60 turned out to be a key hub molecule. IL-1beta induced the expression as well as secretion of HSP60 in extracellular milieu during inflammation of N9 cells. Secreted HSP60 binds to TLR4 and inhibition of TLR4 suppressed IL-1beta induced inflammation to a significant extent. Our knockdown and overexpression studies demonstrated that HSP60 increases the phosphorylation of ERK, JNK, and p38 MAPKs in N9 cells during inflammation. Specific inhibition of p38 by inhibitors suppressed HSP60-induced inflammation, thus pointed towards the major role of p38 MAPK rather than ERK1/2 and JNK in HSP60-induced inflammation. Furthermore, silencing of upstream modulator of p38, i.e., MEK3/6 also reduced HSP60-induced inflammation. CONCLUSIONS: IL-1beta induces expression of HSP60 in N9 microglial cells that further augments inflammation via TLR4-p38 MAPK axis. PMID- 26838599 TI - Liver PPARalpha is crucial for whole-body fatty acid homeostasis and is protective against NAFLD. AB - OBJECTIVE: Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear receptor expressed in tissues with high oxidative activity that plays a central role in metabolism. In this work, we investigated the effect of hepatocyte PPARalpha on non-alcoholic fatty liver disease (NAFLD). DESIGN: We constructed a novel hepatocyte-specific PPARalpha knockout (Pparalpha(hep-/-)) mouse model. Using this novel model, we performed transcriptomic analysis following fenofibrate treatment. Next, we investigated which physiological challenges impact on PPARalpha. Moreover, we measured the contribution of hepatocytic PPARalpha activity to whole-body metabolism and fibroblast growth factor 21 production during fasting. Finally, we determined the influence of hepatocyte-specific PPARalpha deficiency in different models of steatosis and during ageing. RESULTS: Hepatocyte PPARalpha deletion impaired fatty acid catabolism, resulting in hepatic lipid accumulation during fasting and in two preclinical models of steatosis. Fasting mice showed acute PPARalpha-dependent hepatocyte activity during early night, with correspondingly increased circulating free fatty acids, which could be further stimulated by adipocyte lipolysis. Fasting led to mild hypoglycaemia and hypothermia in Pparalpha(hep-/-) mice when compared with Pparalpha(-/-) mice implying a role of PPARalpha activity in non-hepatic tissues. In agreement with this observation, Pparalpha(-/-) mice became overweight during ageing while Pparalpha(hep-/-) remained lean. However, like Pparalpha(-/-) mice, Pparalpha(hep-/-) fed a standard diet developed hepatic steatosis in ageing. CONCLUSIONS: Altogether, these findings underscore the potential of hepatocyte PPARalpha as a drug target for NAFLD. PMID- 26838600 TI - Periodontitis induced by Porphyromonas gingivalis drives periodontal microbiota dysbiosis and insulin resistance via an impaired adaptive immune response. AB - OBJECTIVE: To identify a causal mechanism responsible for the enhancement of insulin resistance and hyperglycaemia following periodontitis in mice fed a fat enriched diet. DESIGN: We set-up a unique animal model of periodontitis in C57Bl/6 female mice by infecting the periodontal tissue with specific and alive pathogens like Porphyromonas gingivalis (Pg), Fusobacterium nucleatum and Prevotella intermedia. The mice were then fed with a diabetogenic/non-obesogenic fat-enriched diet for up to 3 months. Alveolar bone loss, periodontal microbiota dysbiosis and features of glucose metabolism were quantified. Eventually, adoptive transfer of cervical (regional) and systemic immune cells was performed to demonstrate the causal role of the cervical immune system. RESULTS: Periodontitis induced a periodontal microbiota dysbiosis without mainly affecting gut microbiota. The disease concomitantly impacted on the regional and systemic immune response impairing glucose metabolism. The transfer of cervical lymph-node cells from infected mice to naive recipients guarded against periodontitis aggravated metabolic disease. A treatment with inactivated Pg prior to the periodontal infection induced specific antibodies against Pg and protected the mouse from periodontitis-induced dysmetabolism. Finally, a 1-month subcutaneous chronic infusion of low rates of lipopolysaccharides from Pg mimicked the impact of periodontitis on immune and metabolic parameters. CONCLUSIONS: We identified that insulin resistance in the high-fat fed mouse is enhanced by pathogen-induced periodontitis. This is caused by an adaptive immune response specifically directed against pathogens and associated with a periodontal dysbiosis. PMID- 26838601 TI - Integrin signalling regulates the expansion of neuroepithelial progenitors and neurogenesis via Wnt7a and Decorin. AB - Development of the cerebral cortex requires regulation of proliferation and differentiation of neural stem cells and a diverse range of progenitors. Recent work suggests a role for extracellular matrix (ECM) and the major family of ECM receptors, the integrins. Here we show that enhancing integrin beta-1 signalling, by expressing a constitutively active integrin beta-1 (CA*beta1) in the embryonic chick mesencephalon, enhances neurogenesis and increases the number of mitotic cells dividing away from the ventricular surface, analogous to sub-apical progenitors in mouse. Only non-integrin-expressing neighbouring cells (lacking CA*beta1) contributed to the increased neurogenesis. Transcriptome analysis reveals upregulation of Wnt7a within the CA*beta1 cells and upregulation of the ECM protein Decorin in the neighbouring non-expressing cells. Experiments using inhibitors in explant models and genetic knock-downs in vivo reveal an integrin Wnt7a-Decorin pathway that promotes proliferation and differentiation of neuroepithelial cells, and identify Decorin as a novel neurogenic factor in the central nervous system. PMID- 26838603 TI - Congenital central hypoventilation syndrome associated with Hirschsprung's Disease: case report and literature review. AB - OBJECTIVE: To report the case of a newborn with recurrent episodes of apnea, diagnosed with Congenital Central hypoventilation syndrome (CCHS) associated with Hirschsprung's disease (HD), configuring Haddad syndrome. CASE DESCRIPTION: Third child born at full-term to a non-consanguineous couple through normal delivery without complications, with appropriate weight and length for gestational age. Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis. During hospitalization in the NICU, he showed difficulty to undergo extubation due to episodes of desaturation during sleep and wakefulness. He had recurrent episodes of hypoglycemia, hyperglycemia, metabolic acidosis, abdominal distension, leukocytosis, increase in C-reactive protein levels, with negative blood cultures and suspected inborn error of metabolism. At 2 months of age he was diagnosed with long-segment Hirschsprung's disease and was submitted to segment resection and colostomy through Hartmann's procedure. A genetic research was performed by polymerase chain reaction for CCHS screening, which showed the mutated allele of PHOX2B gene, confirming the diagnosis. COMMENTS: This is a rare genetic, autosomal dominant disease, caused by mutation in PHOX2B gene, located in chromosome band 4p12, which results in autonomic nervous system dysfunction. CCHS can also occur with Hirschsprung's disease and tumors derived from the neural crest. There is a correlation between phenotype and genotype, as well as high intrafamilial phenotypic variability. In the neonatal period it can simulate cases of sepsis and inborn errors of metabolism. PMID- 26838602 TI - Chitinases and Imaginal disc growth factors organize the extracellular matrix formation at barrier tissues in insects. AB - The cuticle forms an apical extracellular-matrix (ECM) that covers exposed organs, such as epidermis, trachea and gut, for organizing morphogenesis and protection of insects. Recently, we reported that cuticle proteins and chitin are involved in ECM formation. However, molecular mechanisms that control assembly, maturation and replacement of the ECM and its components are not well known. Here we investigated the poorly described glyco-18-domain hydrolase family in Drosophila and identified the Chitinases (Chts) and imaginal-disc-growth-factors (Idgfs) that are essential for larval and adult molting. We demonstrate that Cht and idgf depletion results in deformed cuticles, larval and adult molting defects, and insufficient protection against wounding and bacterial infection, which altogether leads to early lethality. We show that Cht2/Cht5/Cht7/Cht9/Cht12 and idgf1/idgf3/idgf4/idgf5/idgf6 are needed for organizing proteins and chitin matrix at the apical cell surface. Our data indicate that normal ECM formation requires Chts, which potentially hydrolyze chitin-polymers. We further suggest that the non-enzymatic idgfs act as structural proteins to maintain the ECM scaffold against chitinolytic degradation. Conservation of Chts and Idgfs proposes analogous roles in ECM dynamics across the insect taxa, indicating that Chts/Idgfs are new targets for species specific pest control. PMID- 26838604 TI - Excessive weight loss in exclusively breastfed full-term newborns in a Baby Friendly Hospital. AB - OBJECTIVE: To determine the risk factors for weight loss over 8% in full-term newborns at postpartum discharge from a Baby Friendly Hospital. METHODS: The cases were selected from a cohort of infants belonging to a previous study. Healthy full-term newborns with birth weight >=2.000g, who were exclusively breastfed, and excluding twins and those undergoing phototherapy as well as those discharged after 96 hours of life, were included. The analyzed maternal variables were maternal age, parity, ethnicity, type of delivery, maternal diabetes, gender, gestational age and appropriate weight for age. Adjusted multiple and univariate Cox regression analyses were used, considering as significant p<0.05. RESULTS: We studied 414 newborns, of whom 107 (25.8%) had excessive weight loss. Through the univariate regression, risk factors associated with weight loss >8% were caesarean delivery and older maternal age. At the adjusted multiple regression analysis, the model to explain the weight loss was cesarean delivery (relative risk: 2.27 and 95% of confidence interval: 1.54 to 3.35). CONCLUSIONS: The independent predictor for weight loss >8% in exclusively breastfed full-term newborns in a Baby-Friendly Hospital was the cesarean delivery. It is possible to reduce the number of cesarean sections to minimize neonatal excessive weight loss and the resulting use of infant formula during the first week of life. PMID- 26838605 TI - New multi-scale perspectives on the stromatolites of Shark Bay, Western Australia. AB - A recent field-intensive program in Shark Bay, Western Australia provides new multi-scale perspectives on the world's most extensive modern stromatolite system. Mapping revealed a unique geographic distribution of morphologically distinct stromatolite structures, many of them previously undocumented. These distinctive structures combined with characteristic shelf physiography define eight 'Stromatolite Provinces'. Morphological and molecular studies of microbial mat composition resulted in a revised growth model where coccoid cyanobacteria predominate in mat communities forming lithified discrete stromatolite buildups. This contradicts traditional views that stromatolites with the best lamination in Hamelin Pool are formed by filamentous cyanobacterial mats. Finally, analysis of internal fabrics of stromatolites revealed pervasive precipitation of microcrystalline carbonate (i.e. micrite) in microbial mats forming framework and cement that may be analogous to the micritic microstructures typical of Precambrian stromatolites. These discoveries represent fundamental advances in our knowledge of the Shark Bay microbial system, laying a foundation for detailed studies of stromatolite morphogenesis that will advance our understanding of benthic ecosystems on the early Earth. PMID- 26838606 TI - Patient Characteristics and Outcomes in Adolescents and Young Adults (AYA) With Acute Myeloid Leukemia (AML). AB - BACKGROUND: Little is known about outcomes of acute myeloid leukemia (AML) in adolescents and young adults (AYA). The purpose of this study is to determine the characteristics and outcomes of AYA AML patients in comparison to older adult patients with AML. PATIENTS AND METHODS: We retrospectively analyzed all AML patients treated at our institution from 1965 to 2009 who were aged 16 to 29 years. RESULTS: Among 3922 adult AML patients treated during this period, 432 (11%) were identified as AYA. Median age was 23 years (range, 16-29 years); 73 (17%) patients had core binding factor (CBF)-AML [inversion (16), translocation (8:21)], and 51 (12%) had acute promyelocytic leukemia. Complete remission (CR) rates were 93% for CBF AML, 78% for APL, 77% with diploid karyotype, and 68% for other AML. Univariate analysis demonstrated higher rates of CR, CR duration, and overall survival (OS) in the AYA group compared with older patients. On multivariate analysis, AYA age group was independently associated with improved CR rate and CR duration, with a trend for longer OS (P = .085). CONCLUSION: Outcome of AYA AML patients is overall better than for older adults with AML. Despite improvements in treatments and outcomes over time, there is still need for improvement in AYA with AML particularly for those with AML other than CBF and APL. PMID- 26838607 TI - Demolition waste generation for development of a regional management chain model. AB - Even though construction and demolition waste (CDW) is the bulkiest waste stream, its estimation and composition in specific regions still faces major difficulties. Therefore new methods are required especially when it comes to make predictions limited to small areas, such as counties. This paper proposes one such method, which makes use of data collected from real demolition works and statistical information on the geographical area under study. Based on a correlation analysis between the demolition waste estimates and indicators such as population density, buildings ageing index, buildings density and land occupation type, relationships are established that can be used to determine demolition waste outputs in a given area. The derived models are presented and explained. This methodology is independent from the specific region with which it is exemplified (the Lisbon Metropolitan Area) and can therefore be applied to any region of the world, from the country to the county level. Generation of demolition waste data at the county level is the basis of the design of a systemic model for CDW management in a region. Future developments proposed include a mixed-integer linear programming formulation of such recycling network. PMID- 26838608 TI - Application of landfill treatment approaches for stabilization of municipal solid waste. AB - This research sought to compare the effectiveness of three landfill enhanced treatment approaches aimed at removing releasable carbon and nitrogen after anaerobic landfilling including flushing with clean water (FB 1), leachate recirculation with ex-situ treatment (FB 2), and leachate recirculation with ex situ treatment and in-situ aeration (FB 3). After extensive treatment of the waste in the FB scenarios, the overall solids and biodegradable fraction were reduced relative to the mature anaerobically treated waste. In terms of the overall degradation, aeration did not provide any advantage over flushing and anaerobic treatment. Flushing was the most effective approach at removing biodegradable components (i.e. cellulose and hemicellulose). Leachate quality improved for all FBs but through different mechanisms. A significant reduction in ammonia-nitrogen occurred in FB 1 and 3 due to flushing and aeration, respectively. The reduction of chemical oxygen demand (COD) in FB 1 was primarily due to flushing. Conversely, the reduction in COD in FBs 2 and 3 was due to oxidation and precipitation during Fenton's Reagent treatment. A mass balance on carbon and nitrogen revealed that a significant fraction still remained in the waste despite the additional treatment provided. Carbon was primarily converted biologically to CH4 and CO2 in the FBs or removed during treatment using Fenton's Reagent. The nitrogen removal occurred through leaching or biological conversion. These results show that under extensive treatment the waste and leachate characteristics did meet published stability values. The minimum stability values achieved were through flushing although FB 2 and 3 were able to improve leachate quality and solid waste characteristics but not to the same extent as FB 1. PMID- 26838610 TI - Binding of enterolactone and enterodiol to human serum albumin: increase of cysteine-34 thiol group reactivity. AB - The interaction of polyphenolic molecules with human serum albumin (HSA) could lead to changes in the reactivity of the HSA Cys34 thiol group (HSA-SH). The influences of enterolactone (EL) and enterodiol (ED) binding on HSA-SH reactivity in fatty acid (FA)-free HSA, and in HSA with bound stearic acid (S) in S/HSA molar ratios of 1:1 and 4:1, were investigated by the determination of the pseudo first order rate constants (k') for the thiol reaction with 5,5'-dithiobis-(2 nitrobenzoic acid). The binding affinities and binding sites of EL and ED were also determined, using fluorescence measurements of the intrinsic fluorescence of Trp214 and diazepam (binding site marker). EL and ED binding to HSA increased the reactivity of HSA-SH in all assayed HSA-enterolignan complexes by 9.1-33.1%. The strongest effects were obtained for FA-free HSA-enterolignan complexes. S modulated/reduced the effect of EL on HSA-SH reactivity, while its influence on the effect of ED was negligible. The binding of enterolignans to HSA was investigated: the binding constants were the highest for FA-free HSA (EL: 11.64 * 10(4) M(-1) and ED: 5.59 * 10(4) M(-1) at 37 degrees C) and the lowest for S/HSA 4:1-enterolignan complexes (EL: 2.43 * 10(4) M(-1) and ED: 1.92 * 10(4) M(-1)). When the S/HSA ratio was increased, the binding affinities and number of binding sites for EL and ED were decreased. At the same time, a high correlation between binding constants and increased Cys34 reactivity was found (r = 0.974). Competitive experiments using diazepam indicated that the binding of ED and of EL was located in the hydrophobic pocket of site II in HSA. Overall, it is evident that stearic acid could modulate the enterolignan effects on HSA-SH reactivity as well as their binding to HSA. This finding could be important for pharmacokinetics and the expression of enterolignan antioxidant effects in vivo after an intake of lignan rich food. PMID- 26838609 TI - Monitoring/characterization of stickies contaminants coming from a papermaking plant--Toward an innovative exploitation of the screen rejects to levulinic acid. AB - Recycled paper needs a lot of mechanical/chemical treatments for its re-use in the papermaking process. Some of these ones produce considerable rejected waste fractions, such as "screen rejects", which include both cellulose fibers and non fibrous organic contaminants, or "stickies", these last representing a shortcoming both for the papermaking process and for the quality of the final product. Instead, the accepted fractions coming from these unit operations become progressively poorer in contaminants and richer in cellulose. Here, input and output streams coming from mechanical screening systems of a papermaking plant using recycled paper for cardboard production were sampled and analyzed directly and after solvent extraction, thus confirming the abundant presence of styrene butadiene rubber (SBR) and ethylene vinyl acetate (EVA) copolymers in the output rejected stream and cellulose in the output accepted one. Despite some significant drawbacks, the "screen reject" fraction could be traditionally used as fuel for energy recovery within the paper mill, in agreement with the integrated recycled paper mill approach. The waste, which still contains a cellulose fraction, can be also exploited by means of the hydrothermal route to give levulinic acid, a platform chemical of very high value added. PMID- 26838612 TI - DH might secure student bursary cut and bypass Commons vote. AB - Unions are concerned that the government will push through plans to scrap the nursing student bursary despite any opposition presented in a public consultation. PMID- 26838611 TI - Perhaps we're not as accepting as we think. AB - Fans of the BBC drama series Call the Midwife may be spending their Sunday evenings wondering why some people living only half a century ago were so cruel and unforgiving of those who did not conform to societal norms. PMID- 26838614 TI - 'Nurses and paramedics should be the only call handlers at NHS 111'. AB - A mother whose baby son died of sepsis following 'missed opportunities' in the NHS has called for the 111 hotline to be staffed solely by clinicians. PMID- 26838615 TI - RCN Scotland calls on politicians to show their support for nursing issues. AB - RCN Scotland is calling on candidates standing for election to the Scottish parliament later this year to support key nursing issues. PMID- 26838616 TI - No overlap between nurse and associate role--HEE. AB - Health Education England said it does not believe the tasks undertaken in the proposed nursing associate role would overlap with those of nurses. PMID- 26838618 TI - NMC to modernise its standards for pre-reg education. AB - The Nursing and Midwifery Council has announced it will develop new standards for pre-registration nurse education. PMID- 26838620 TI - Infection prevention toolkit targets pneumonia and UTIs. AB - The RCN is emphasising the importance of infection prevention with the launch of a toolkit. PMID- 26838622 TI - Mental health nursing workforce under pressure as numbers slump. AB - The number of mental health nurses in England has fallen, leaving the remaining nursing workforce to 'bear the brunt' of increasing pressures, the RCN has warned. PMID- 26838624 TI - Safe staffing guidance still elusive--three years on from Mid Staffs. AB - Evidence reviews into safe nurse staffing that reveal gaps in available information have led to calls for urgent progress to be made on the issue. PMID- 26838630 TI - Sepsis. AB - Each year in the UK there are an estimated 150,000 cases of sepsis, and 44,000 people die as a result of the condition (UK Sepsis Trust). Sepsis is triggered by an infection that causes the immune system to attack the body's own tissues. If not treated quickly, it can lead to multiple organ failure and death. PMID- 26838631 TI - Zero tolerance for unhealthy attitudes. AB - A report published last year by Stonewall revealed the persistence of negative attitudes to LGBT people in health and social care services, with a significant problem existing between staff. Managers' failure to support employees and challenge remarks, however subtle, are part of the problem. PMID- 26838632 TI - LGBT youth missing out on support. AB - According to a Department of Health-funded study young LGBT people are at increased risk of self-harm and suicide. The Queer Futures project has also revealed that mental health professionals lack access to the training they need to support these young people. PMID- 26838633 TI - Shock therapies. AB - Therapies administered by mental health nurses, aimed at "curing" gay people of their sexual preference were still in common use in the UK in the 1960s and early 1970s. Some nurses tried to avoid participating in these practices, but many believed that they were helping their patients, as a new book reveals. PMID- 26838647 TI - Catheter procedures expose variations in nurse practice. PMID- 26838648 TI - It is vital that we have input on nursing associate consultation. PMID- 26838651 TI - Hands up who thinks nurses are well paid in Northern Ireland. PMID- 26838650 TI - Let's keep a record of how we work so nursing isn't airbrushed from history. PMID- 26838652 TI - Consider deeper implications of the effects of domestic abuse. PMID- 26838655 TI - How to perform irrigation of the eye. AB - rationale and key points: This article aims to help nurses to understand the importance of performing irrigation immediately following chemical injury to the eye, and outlines the most effective technique. It is essential that irrigation of the eye is understood and performed correctly. Chemical injury to the eye is an ophthalmic emergency. It presents a serious risk to the patient's vision and may cause blindness. The length of time the chemical remains in contact with the eye determines the severity of the injury. Immediate irrigation of the eye is essential to minimise preventable loss of vision. REFLECTIVE ACTIVITY: Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. How you would ensure immediate irrigation following chemical injury to the eye in your clinical area. 2. How you know when you have irrigated the eye for long enough, if you have previously performed this procedure, and how reading this article might influence your practice. Subscribers can upload their reflective accounts at: rcni.com/portfolio . PMID- 26838656 TI - Palliative and end of life care for people with dementia. AB - Dementia is a life-limiting condition that is largely a disease of ageing. However, older people in general, and older people with dementia in particular, have not always had equal access to effective palliative and end of life care. As a result, people with dementia at the end of life often receive aggressive and burdensome interventions, or inadequate assessment and management of their symptoms. Patterns in how people with dementia experience and present symptoms as they near the end of life can indicate when the goals of care should change and a palliative approach should be adopted. PMID- 26838658 TI - Encephalitis. AB - The CPD article provided information on encephalitis and focused on prioritising people and addressing the needs of the patient, their family and carers. The article encourages nurses to ensure that the fundamentals of care are delivered effectively and that physical, psychological and social needs are addressed. PMID- 26838659 TI - Make a CV work harder. AB - Many applications for nursing posts will be through website forms, but writing and updating CVs is a useful aid to a job search, according to experts in nursing recruitment. PMID- 26838657 TI - Acute pulmonary oedema. AB - Acute pulmonary oedema is a distressing and life-threatening illness that is associated with a sudden onset of symptoms. For the best possible patient outcomes, it is essential that nurses in all clinical areas are equipped to accurately recognise, assess and manage patients with acute pulmonary oedema. This article outlines the pathophysiology of acute cardiogenic and non cardiogenic pulmonary oedema, and suggests a systematic approach to the recognition and management of its most serious manifestations. Long-term care and symptom recognition are discussed and suggestions for ongoing patient self management are provided. PMID- 26838661 TI - Care for all sexual orientations. AB - Establishing a rapport with a trans* patient is a vital aspect of health care. It encourages trust and helps build confidence, but for many nurses there is a fear of getting it wrong. PMID- 26838662 TI - Student life--Homophobia is just poor care by another name. AB - Prejudiced attitudes harm patient care as well as staff relations, and it is time for professionals to speak up about it. PMID- 26838663 TI - Delayed Stenting for ST-Elevation Acute Myocardial Infarction in Daily Practice: A Single-Centre Experience. AB - BACKGROUND: The minimalist immediate mechanical intervention (MIMI) strategy aims to restore normal anterograde flow in the culprit artery (by using manual thrombectomy or small-sized balloon predilation) and to defer potential stent implantation. This study evaluated the applicability and midterm clinical results of the MIMI strategy for ST-elevation myocardial infarction (STEMI) management. METHODS: This observational study included consecutive patients admitted for ongoing STEMI (<24 hours' evolution) at 1 institution between June 2010 and June 2013. Revascularization was performed at the physician's discretion. We compared retrospectively "intentional immediate stenting" (standard technique) and "intentional delayed stenting" (MIMI technique). RESULTS: Twenty percent of the 279 included patients were treated with the MIMI strategy. These patients were significantly younger and were more frequently men and smokers compared with patients who underwent the standard procedure. The rate of acute reocclusion of the culprit artery related to STEMI in the MIMI group was 1.8%. Drug-eluting stents were used more frequently in the MIMI group (52% vs 27% in the standard group; P < 0.001). The culprit lesion was stented less frequently in the patients treated with MIMI compared with patients in the other group (28.5% vs 9%; P < 0.001). The 1-year actuarial survival free from major adverse cardiovascular events was higher in the MIMI group than in the standard group (96.3% +/- 1.8% vs 83.8% +/- 2.5%; P = 0.01). CONCLUSIONS: The MIMI strategy can be applied in selected patients with STEMI. In our centre, this strategy is associated with less systematic culprit lesion stenting and more implantation of drug-eluting stents. However, this needs to be evaluated further in a randomized trial. PMID- 26838664 TI - Beating Heart Minimally Invasive Mitral Valve Surgery in Patients With Patent Coronary Bypass Grafts. AB - BACKGROUND: Redo mitral valve surgery in patients with patent coronary bypass grafts carries a risk of graft injury and postoperative bleeding. We compare early results of reoperative minimally invasive on-pump beating heart mitral valve surgery (OPBMS) via mini thoracotomy vs the results of standard sternotomy mitral valve surgery (SSMS) in the presence of patent coronary bypass grafts. METHODS: Between 2009 and 2015, 12 patients underwent OPBMS through a right mini thoracotomy and 6 patients underwent SSMS. All patients had at least 1 patent bypass graft. RESULTS: Median age and EuroSCORE II were not statistically different between the 2 groups. There was no early death in the OPBMS group vs 1 death (17%) in the SSMS group. There was a statistically significant lower median perioperative blood loss in the OPBMS group compared with the SSMS group (200 vs 650 mL; P = 0.005). Four patients (33%) in the OPBMS group required blood transfusion compared with 4 in the SSMS group (67%; P = 0.32). There was 1 perioperative stroke (17%) and 1 acute myocardial infarction (17%) in the SSMS group. Four patients developed acute renal failure in the OPBMS group compared with 3 in the SSMS group (50%; P = 0.62). The predischarge transthoracic echocardiogram showed <= 1 mitral regurgitation in all patients. CONCLUSIONS: Redo mitral surgery in patients with patent bypass grafts can safely be performed via minimally invasive mini thoracotomy on a beating heart. The main benefits of this approach are to avoid the sternotomy and decrease the amount of postoperative blood loss. PMID- 26838666 TI - The morphology of high frequency oscillations (HFO) does not improve delineating the epileptogenic zone. AB - OBJECTIVE: We hypothesized that high frequency oscillations (HFOs) with irregular amplitude and frequency more specifically reflect epileptogenicity than HFOs with stable amplitude and frequency. METHODS: We developed a fully automatic algorithm to detect HFOs and classify them based on their morphology, with types defined according to regularity in amplitude and frequency: type 1 with regular amplitude and frequency; type 2 with irregular amplitude, which could result from filtering of sharp spikes; type 3 with irregular frequency; and type 4 with irregular amplitude and frequency. We investigated the association of different HFO types with the seizure onset zone (SOZ), resected area and surgical outcome. RESULTS: HFO rates of all types were significantly higher inside the SOZ than outside. HFO types 1 and 2 were strongly correlated to each other and showed the highest rates among all HFOs. Their occurrence was highly associated with the SOZ, resected area and surgical outcome. The automatic detection emulated visual markings with 93% true positives and 57% false detections. CONCLUSIONS: HFO types 1 and 2 similarly reflect epileptogenicity. SIGNIFICANCE: For clinical application, it may not be necessary to separate real HFOs from "false oscillations" produced by the filter effect of sharp spikes. Also for automatically detected HFOs, surgical outcome is better when locations with higher HFO rates are included in the resection. PMID- 26838665 TI - Crossover from polariton lasing to exciton lasing in a strongly coupled ZnO microcavity. AB - Unlike conventional photon lasing, in which the threshold is limited by the population inversion of the electron-hole plasma, the exciton lasing generated by exciton-exciton scattering and the polariton lasing generated by dynamical condensates have received considerable attention in recent years because of the sub-Mott density and low-threshold operation. This paper presents a novel approach to generate both exciton and polariton lasing in a strongly coupled microcavity (MC) and determine the critical driving requirements for simultaneously triggering these two lasing operation in temperature <140 K and large negative polariton-exciton offset (<-133 meV) conditions. In addition, the corresponding lasing behaviors, such as threshold energy, linewidth, phase diagram, and angular dispersion are verified. The results afford a basis from which to understand the complicated lasing mechanisms in strongly coupled MCs and verify a new method with which to trigger dual laser emission based on exciton and polariton. PMID- 26838667 TI - Hydrogen sensing with Pd-coated long-range surface plasmon membrane waveguides. AB - A low power, reusable optical hydrogen sensor using long-range surface plasmon polariton (LRSPP) cladded membrane waveguides is demonstrated. The sensor incorporates a 5 MUm wide, 20 nm thick gold stripe embedded in a 160 nm thick free-standing Cytop membrane with a 5 nm thick Pd over-layer. Input and output coupling is achieved with directly integrated broadside grating couplers. The sensor is tested with hydrogen concentrations up to 3% and demonstrates a strong response with an estimated detection limit of 290 ppm, and a response time of 7 s to a 0.6% H2 step - this level of performance is among the best reported for optical H2 sensors. Cycling of the hydrogen exposure shows a significant hysteresis response, however no film deformation or delamination was observed over many cycles. The high stress that is induced in clamped films during hydrogenation is relaxed in due to the film being deposited on the flexible and elastic Cytop membrane. This could result in improved lifetimes for this sensor and increased uptake ability. PMID- 26838669 TI - Metabolic syndrome and eye diseases. AB - Metabolic syndrome is becoming a worldwide medical and public health challenge as it has been seen increasing in prevalence over the years. Age-related eye diseases, the leading cause of blindness globally and visual impairment in developed countries, are also on the rise due to aging of the population. Many of the individual components of the metabolic syndrome have been shown to be associated with these eye diseases. However, the association of metabolic syndrome with eye diseases is not clear. In this review, we reviewed the evidence for associations between metabolic syndrome and certain ocular diseases in populations. We also reviewed the association of individual metabolic syndrome components with ocular diseases due to a paucity of research in this area. Besides, we also summarised the current understanding of etiological mechanisms of how metabolic syndrome or the individual components lead to these ocular diseases. With increasing evidence of such associations, it may be important to identify patients who are at risk of developing metabolic syndrome as prompt treatment and intervention may potentially decrease the risk of developing certain ocular diseases. PMID- 26838668 TI - The prognostic significance of admission blood glucose levels in patients with urinary tract infection. AB - AIMS: Evaluate the association between admission blood glucose (ABG) and short and long-term outcomes following hospitalization for urinary tract infection (UTI). METHODS: Single center, retrospective cohort study of patients admitted to medical wards between January 1, 2011 and December 31, 2013 with a diagnosis of UTI. Patients were classified to those with diabetes mellitus (DM) and those without it. ABG levels were classified to categories: <=70, 70-110, 111-199, >=200mg/dl. Primary outcome was all-cause mortality within 30-days and 1-year. Secondary outcomes were hospital readmissions within 30-days and 1-year, and survival rates at end of follow-up. RESULTS: Cohort included 3405 patients (median age, 78 years; 44% men), 1106 with DM and 2299 without it. Among patients without DM, compared with ABG between 70 and 110mg/dl (n=852, 37%), there was a significant association between ABG and all-cause mortality: hazard ratios (95% CI) with ABG <=70mg/dl (n=13, 0.6%), 111-199mg/dl (n=1292, 56%), and >=200mg/dl (n=142, 6%) were: 3.67 (0.89-15.14, p=0.07, 23% mortality (n=3)), 1.85 (1.29 2.64, p<0.001, 7% mortality (n=89)), and 2.94 (1.71-5.07, p<0.0001, 11% mortality (n=15)) at 30-days, and 3.8 (1.87-7.71, 38% mortality (n=5)), 1.35 (1 1.13-1.60, 7% mortality (n=215)), and 2.02 (1.50-2.71, 25% mortality (n=35)) at 1-year (all p<0.001). In patients with DM there was no significant association between ABG and mortality. There was no association between ABG and readmissions in both groups. CONCLUSION: There is a significant association between ABG and short and long-term, all-cause mortality in patients without DM, but not in patients with DM, hospitalized for UTI. PMID- 26838670 TI - Simple understanding of quantum weak values. AB - In this work we revisit the important and controversial concept of quantum weak values, aiming to provide a simplified understanding to its associated physics and the origin of anomaly. Taking the Stern-Gerlach setup as a working system, we base our analysis on an exact treatment in terms of quantum Bayesian approach. We also make particular connection with a very recent work, where the anomaly of the weak values was claimed from the pure statistics in association with "disturbance" and "post-selection", rather than the unique quantum nature. Our analysis resolves the related controversies through a clear and quantitative way. PMID- 26838671 TI - Host-derived glycans serve as selected nutrients for the gut microbe: human milk oligosaccharides and bifidobacteria. AB - Lactation is a common feeding strategy of eutherian mammals, but its functions go beyond feeding the neonates. Ever since Tissier isolated bifidobacteria from the stool of breast-fed infants, human milk has been postulated to contain compounds that selectively stimulate the growth of bifidobacteria in intestines. However, until relatively recently, there have been no reports to link human milk compound(s) with bifidobacterial physiology. Over the past decade, successive studies have demonstrated that infant-gut-associated bifidobacteria are equipped with genetic and enzymatic toolsets dedicated to assimilation of host-derived glycans, especially human milk oligosaccharides (HMOs). Among gut microbes, the presence of enzymes required for degrading HMOs with type-1 chains is essentially limited to infant-gut-associated bifidobacteria, suggesting HMOs serve as selected nutrients for the bacteria. In this study, I shortly discuss the research on bifidobacteria and HMOs from a historical perspective and summarize the roles of bifidobacterial enzymes in the assimilation of HMOs with type-1 chains. Based on this overview, I suggest the co-evolution between bifidobacteria and human beings mediated by HMOs. PMID- 26838673 TI - Steric interactions lead to collective tilting motion in the ribosome during mRNA tRNA translocation. AB - Translocation of mRNA and tRNA through the ribosome is associated with large scale rearrangements of the head domain in the 30S ribosomal subunit. To elucidate the relationship between 30S head dynamics and mRNA-tRNA displacement, we apply molecular dynamics simulations using an all-atom structure-based model. Here we provide a statistical analysis of 250 spontaneous transitions between the A/P-P/E and P/P-E/E ensembles. Consistent with structural studies, the ribosome samples a chimeric ap/P-pe/E intermediate, where the 30S head is rotated ~18 degrees . It then transiently populates a previously unreported intermediate ensemble, which is characterized by a ~10 degrees tilt of the head. To identify the origins of head tilting, we analyse 781 additional simulations in which specific steric features are perturbed. These calculations show that head tilting may be attributed to specific steric interactions between tRNA and the 30S subunit (PE loop and protein S13). Taken together, this study demonstrates how molecular structure can give rise to large-scale collective rearrangements. PMID- 26838674 TI - Hepatogenic differentiation from human adipose-derived stem cells and application for mouse acute liver injury. AB - Adipose-derived stem cells (ADSCs) derived from adipose tissue have the capacity to differentiate into endodermal, mesoderm, and ectodermal cell lineages in vitro, which are an ideal engraft in tissue-engineered repair. In this study, human ADSCs were isolated from subcutaneous fat. The markers of ADSCs, CD13, CD71, CD73, CD90, CD105, CD166, CYP3A4, and ALB were detected by immunofluorescence assays. Human ADSCs were cultured in a specific hepatogenesis differentiation medium containing HGF, bFGF, nicotinamide, ITS, and oncostatin M for hepatogenic differentiation. The hepatocyte markers were analyzed using immunofluorescence and real-time PCR after dramatic changes in morphology. Hepatocytes derived from ADSCs or ADSCs were transplanted into the mice of liver injury for observation cells colonization and therapy in liver tissue. The result demonstrated that human ADSCs were positive for the CD13, CD71, CD73, CD90, CD105, and CD166 but negative for hepatocyte markers, ALB and CYP3A4. After hepatogenic differentiation, the hepatocytes were positive for liver special markers, gene expression level showed a time-lapse increase with induction time. Human ADSCs or ADSCs-derived hepatocyte injected into the vein could improve liver function repair and functionally rescue the CCl4-treated mice with liver injury, but the ADSCs transplantation was better than ADSCs-derived hepatocyte transplantation. In conclusion, our research shows that a population of hepatocyte can be specifically generated from human ADSCs and that cells may allow for participation in tissue-repair. PMID- 26838672 TI - Downregulation of TLX induces TET3 expression and inhibits glioblastoma stem cell self-renewal and tumorigenesis. AB - Glioblastomas have been proposed to be maintained by highly tumorigenic glioblastoma stem cells (GSCs) that are resistant to current therapy. Therefore, targeting GSCs is critical for developing effective therapies for glioblastoma. In this study, we identify the regulatory cascade of the nuclear receptor TLX and the DNA hydroxylase Ten eleven translocation 3 (TET3) as a target for human GSCs. We show that knockdown of TLX expression inhibits human GSC tumorigenicity in mice. Treatment of human GSC-grafted mice with viral vector-delivered TLX shRNA or nanovector-delivered TLX siRNA inhibits tumour development and prolongs survival. Moreover, we identify TET3 as a potent tumour suppressor downstream of TLX to regulate the growth and self-renewal in GSCs. This study identifies the TLX-TET3 axis as a potential therapeutic target for glioblastoma. PMID- 26838675 TI - Neural network-based robust actuator fault diagnosis for a non-linear multi-tank system. AB - The paper is devoted to the problem of the robust actuator fault diagnosis of the dynamic non-linear systems. In the proposed method, it is assumed that the diagnosed system can be modelled by the recurrent neural network, which can be transformed into the linear parameter varying form. Such a system description allows developing the designing scheme of the robust unknown input observer within Hinfinity framework for a class of non-linear systems. The proposed approach is designed in such a way that a prescribed disturbance attenuation level is achieved with respect to the actuator fault estimation error, while guaranteeing the convergence of the observer. The application of the robust unknown input observer enables actuator fault estimation, which allows applying the developed approach to the fault tolerant control tasks. PMID- 26838677 TI - A rhodium(I)-oxygen adduct as a selective catalyst for one-pot sequential alkyne dimerization-hydrothiolation tandem reactions. AB - An air-stable rhodium(I)-oxygen adduct featuring a CNC-pincer ligand, based on 1,2,3-triazol-5-ylidenes, catalyzes the homo-dimerization and hydrothiolation of alkynes, affording the gem-enyne and alpha-vinyl sulfide isomers, respectively, with excellent selectivity. A one-pot stepwise strategy allows the selective catalytic preparation of non-symmetric bis-vinyl sulfides, as well as the alkyne dimerization-hydrothiolation tandem reactions. PMID- 26838676 TI - A visual and curatorial approach to clinical variant prioritization and disease gene discovery in genome-wide diagnostics. AB - BACKGROUND: Genome-wide data are increasingly important in the clinical evaluation of human disease. However, the large number of variants observed in individual patients challenges the efficiency and accuracy of diagnostic review. Recent work has shown that systematic integration of clinical phenotype data with genotype information can improve diagnostic workflows and prioritization of filtered rare variants. We have developed visually interactive, analytically transparent analysis software that leverages existing disease catalogs, such as the Online Mendelian Inheritance in Man database (OMIM) and the Human Phenotype Ontology (HPO), to integrate patient phenotype and variant data into ranked diagnostic alternatives. METHODS: Our tool, "OMIM Explorer" ( http://www.omimexplorer.com ), extends the biomedical application of semantic similarity methods beyond those reported in previous studies. The tool also provides a simple interface for translating free-text clinical notes into HPO terms, enabling clinical providers and geneticists to contribute phenotypes to the diagnostic process. The visual approach uses semantic similarity with multidimensional scaling to collapse high-dimensional phenotype and genotype data from an individual into a graphical format that contextualizes the patient within a low-dimensional disease map. The map proposes a differential diagnosis and algorithmically suggests potential alternatives for phenotype queries--in essence, generating a computationally assisted differential diagnosis informed by the individual's personal genome. Visual interactivity allows the user to filter and update variant rankings by interacting with intermediate results. The tool also implements an adaptive approach for disease gene discovery based on patient phenotypes. RESULTS: We retrospectively analyzed pilot cohort data from the Baylor Miraca Genetics Laboratory, demonstrating performance of the tool and workflow in the re-analysis of clinical exomes. Our tool assigned to clinically reported variants a median rank of 2, placing causal variants in the top 1 % of filtered candidates across the 47 cohort cases with reported molecular diagnoses of exome variants in OMIM Morbidmap genes. Our tool outperformed Phen-Gen, eXtasy, PhenIX, PHIVE, and hiPHIVE in the prioritization of these clinically reported variants. CONCLUSIONS: Our integrative paradigm can improve efficiency and, potentially, the quality of genomic medicine by more effectively utilizing available phenotype information, catalog data, and genomic knowledge. PMID- 26838678 TI - Oxethazaine inhibits hepatitis B virus capsid assembly by blocking the cytosolic calcium-signalling pathway. AB - Chronic hepatitis B virus (HBV) infection is a serious public health problem and may progress to liver fibrosis, cirrhosis and hepatocellular carcinoma. It is currently treated with PEGylated IFN-alpha2a and nucleoside/nucleotide analogues (NAs). However, PEGylated IFN treatment has problems of high cost, low efficiency and side effects. Long-term administration of NAs is necessary to avoid virus relapse, which can cause drug resistance and side effects. New efforts are now being directed to develop novel anti-HBV drugs targeting either additional viral targets other than viral DNA polymerase or host targets to improve the treatment of chronic hepatitis B. In this study, we discovered that oxethazaine, approved for clinic use in a few countries such as Japan, India, South Africa and Brazil, can dose-dependently reduce the levels of HBV envelope antigen, extracellular HBV DNA in supernatants and intracellular HBV total DNA. However, the levels of HBV cccDNA and HBV RNAs were not affected by oxethazaine treatment. Further study confirmed that oxethazaine acts on the virus assembly stage of the HBV life cycle. A study of the mechanisms of oxethazaine suggested that this drug inhibits HBV replication and capsid assembly by blocking the cytosolic calcium-signalling pathway. Moreover, oxethazaine could inhibit the replication of lamivudine/entecavir-dual-resistant and adefovir-resistant HBV mutants. In conclusion, our study suggests that oxethazaine may serve as a promising drug, or could be used as a starting point for anti-HBV drug discovery. PMID- 26838679 TI - Iodine deficiency induces a VEGF-dependent microvascular response in salivary glands and in the stomach. AB - Despite efforts to optimize iodine supply in iodine deficient countries, iodine deficiency (ID) remains a global problem worldwide. Activation of the local microvasculature by ID in the thyroid gland aims at improving the local supply of iodide. For this purpose, the thyrocytes secrete vascular endothelial growth factor (VEGF) that acts on adjacent capillaries, via a reactive oxygen species (ROS)/Hypoxia Inducible factor (HIF)-dependent pathway. Beside the thyroid, other organs including salivary glands and the stomach do express the sodium/iodide symporter (NIS) and are able to take iodide up, potentially rendering them sensitive to ID. To verify this hypothesis, ID-induced effects on the local microvasculature were studied in salivary glands and in the stomach. ID was induced by feeding young mice with an iodide-deficient diet and NIS inhibitor perchlorate in the drinking water. In salivary glands, ID induced a transient increase in HIF-1alpha protein expression accompanied by a transient, VEGF dependent increase in blood flow. In the gastric mucosa, ID transiently increased VEGF expression in the mucin-secreting epithelium and in ghrelin-secreting endocrine cells. These observations suggest that microvascular changes in response to ID occur in NIS-expressing tissues other than the thyroid. NIS expressing cells could be viewed as iodide sensors that respond to ID by inducing vascular changes, probably to optimize iodide bioavailability at regional or systemic levels. PMID- 26838682 TI - Dynamics of heart rate variability analysed through nonlinear and linear dynamics is already impaired in young type 1 diabetic subjects. AB - BACKGROUND: Autonomic diabetic neuropathy is one of the most common complications of type 1 diabetes mellitus, and studies using heart rate variability to investigate these individuals have shown inconclusive results regarding autonomic nervous system activation. Aims To investigate the dynamics of heart rate in young subjects with type 1 diabetes mellitus through nonlinear and linear methods of heart rate variability. METHODS: We evaluated 20 subjects with type 1 diabetes mellitus and 23 healthy control subjects. We obtained the following nonlinear indices from the recurrence plot: recurrence rate (REC), determinism (DET), and Shanon entropy (ES), and we analysed indices in the frequency (LF and HF in ms2 and normalised units - nu - and LF/HF ratio) and time domains (SDNN and RMSSD), through analysis of 1000 R-R intervals, captured by a heart rate monitor. RESULTS: There were reduced values (p<0.05) for individuals with type 1 diabetes mellitus compared with healthy subjects in the following indices: DET, REC, ES, RMSSD, SDNN, LF (ms2), and HF (ms2). In relation to the recurrence plot, subjects with type 1 diabetes mellitus demonstrated lower recurrence and greater variation in their plot, inter-group and intra-group, respectively. CONCLUSION: Young subjects with type 1 diabetes mellitus have autonomic nervous system behaviour that tends to randomness compared with healthy young subjects. Moreover, this behaviour is related to reduced sympathetic and parasympathetic activity of the autonomic nervous system. PMID- 26838680 TI - Glutathione S-Transferase P-Mediated Protein S-Glutathionylation of Resident Endoplasmic Reticulum Proteins Influences Sensitivity to Drug-Induced Unfolded Protein Response. AB - AIMS: S-glutathionylation of cysteine residues, catalyzed by glutathione S transferase Pi (GSTP), alters structure/function characteristics of certain targeted proteins. Our goal is to characterize how S-glutathionylation of proteins within the endoplasmic reticulum (ER) impact cell sensitivity to ER stress inducing drugs. RESULTS: We identify GSTP to be an ER-resident protein where it demonstrates both chaperone and catalytic functions. Redox based proteomic analyses identified a cluster of proteins cooperatively involved in the regulation of ER stress (immunoglobulin heavy chain-binding protein [BiP], protein disulfide isomerase [PDI], calnexin, calreticulin, endoplasmin, sarco/endoplasmic reticulum Ca2+-ATPase [SERCA]) that individually co immunoprecipitated with GSTP (implying protein complex formation) and were subject to reactive oxygen species (ROS) induced S-glutathionylation. S glutathionylation of each of these six proteins was attenuated in cells (liver, embryo fibroblasts or bone marrow dendritic) from mice lacking GSTP (Gstp1/p2-/-) compared to wild type (Gstp1/p2+/+). Moreover, Gstp1/p2-/- cells were significantly more sensitive to the cytotoxic effects of the ER-stress inducing drugs, thapsigargin (7-fold) and tunicamycin (2-fold). INNOVATION: Within the family of GST isozymes, GSTP has been ascribed the broadest range of catalytic and chaperone functions. Now, for the first time, we identify it as an ER resident protein that catalyzes S-glutathionylation of critical ER proteins within this organelle. Of note, this can provide a nexus for linkage of redox based signaling and pathways that regulate the unfolded protein response (UPR). This has novel importance in determining how some drugs kill cancer cells. CONCLUSIONS: Contextually, these results provide mechanistic evidence that GSTP can exert redox regulation in the oxidative ER environment and indicate that, within the ER, GSTP influences the cellular consequences of the UPR through S glutathionylation of a series of key interrelated proteins. Antioxid. Redox Signal. 26, 247-261. PMID- 26838683 TI - Novel diagnostic techniques for celiac disease. AB - The diagnosis of celiac disease has long been based on the demonstration of gluten-induced small-bowel mucosal damage. However, due to the constantly increasing disease prevalence and limitations in the histology-based criteria there is a pressure towards more serology-based diagnostics. The serological tools are being improved and new non-invasive methods are being developed, but the constantly refined endoscopic and histologic techniques may still prove helpful. Moreover, growing understanding of the disease pathogenesis has led researchers to suggest completely novel approaches to celiac disease diagnostics regardless of disease activity. In this review, we will elucidate the most recent development and possible future innovations in the diagnostic techniques for celiac disease. PMID- 26838681 TI - Provider communication about HPV vaccination: A systematic review. AB - BACKGROUND: Improving HPV vaccination coverage in the US will require healthcare providers to recommend the vaccine more effectively. To inform quality improvement efforts, we systematically reviewed studies of provider communication about HPV vaccination. METHODS: We searched MEDLINE, CINAHL, EMBASE, and POPLINE in August 2015 to identify studies of provider communication about HPV vaccination. RESULTS: We identified 101 qualitative and quantitative studies. Providers less often recommended HPV vaccine if they were uncomfortable discussing sex, perceived parents as hesitant, or believed patients to be low risk. Patients less often received recommendations if they were younger, male, or from racial/ethnic minorities. Despite parents' preference for unambiguous recommendations, providers often sent mixed messages by failing to endorse HPV vaccine strongly, differentiating it from other vaccines, and presenting it as an "optional" vaccine that could be delayed. CONCLUSION: Interventions are needed to help providers deliver effective recommendations in the complex communication environment surrounding HPV vaccination. PMID- 26838684 TI - Fruit and vegetable intake and vitamin C transporter gene (SLC23A2) polymorphisms in chronic lymphocytic leukaemia. AB - PURPOSE: There is currently no convincing epidemiological evidence that fruit and vegetable consumption, the primary source of vitamin C, plays a role in chronic lymphocytic leukaemia (CLL) aetiology. We hypothesized that variations in vitamin C dietary intake as well as in genetic variability in vitamin C transporter gene SLC23A2 could explain some inconsistencies in the literature. METHODS: Fruit/vegetable/vitamin C consumption from food frequency questionnaires and six low-penetrance genetic susceptibility polymorphisms in vitamin C transporter gene SLC23A2 (rs1715364, rs6133175, rs1776948, rs6139587, rs369270 and rs6052937) were examined in 434 CLL cases and 1257 randomly selected controls from primary care centres with genetic data of whom 275 cases and 1094 controls having both diet and genetic information. Logistic regression models were used to estimate odds ratio (OR) and 95 % confidence intervals (CI). RESULTS: CLL patients were more likely to have a higher fruit consumption than controls (highest versus lowest quartile in g/day OR: 1.48; 95 % CI: 1.00 to 2.18; P = 0.03), whereas no associations were found with vegetable or total vitamin C intake. Based on log additive models, rs6133175_A > G (OR: 1.19, 95 % CI: 1.00 to 1.41; P = 0.05) and rs1776948_T > A (OR: 1.20; 95 %CI: 1.01 to 1.41; P = 0.04) were associated with CLL. The haplogenotype analysis (rs1715364, rs6133175) supported the genotype results. No gene-diet interactions in CLL remained statistically significant after correction for multiple testing. CONCLUSIONS: These data suggest that both fruit intake and genetic marker in SLC23A2 may play an independent role in CLL biology. PMID- 26838685 TI - A population-based study of aerococcal bacteraemia in the MALDI-TOF MS-era. AB - The purpose of this study was to determine the incidence of aerococcal bacteraemia in the MALDI-TOF MS-era, to describe the clinical presentation and to determine the MIC values of aerococci for ten antibiotics. Aerococci in blood cultures were identified through searches in the laboratory database for the years 2012-2014. MALDI-TOF MS, sequencing of the 16S rRNA gene and a PYR test were used for species identification. Patients' medical charts were systematically reviewed. Etests were used to determine MIC values. Seventy-seven patients were identified (Aerococcus urinae n = 49, Aerococcus viridans n = 14, Aerococcus sanguinicola n = 13 and Aerococcus christensenii n = 1) corresponding to incidences of 14 cases per 1,000,000 inhabitants per year (A. urinae) and 3.5 cases per 1,000,000 inhabitants per year (A. sanguinicola and A.viridans). A. urinae was in pure culture in 61 %, A. sanguinicola in 46 % and A. viridans in 36 % of the cases. The A. urinae and A. sanguinicola patients were old and many had urinary tract disorders, and a majority had a suspected urinary tract focus of the bacteraemia. Eighty percent of the A. urinae patients were men. Five A. urinae patients were diagnosed with infective endocarditis. Six patients died within 30 days. Most isolates had low MICs to penicillins and carbapenems. MALDI TOF MS has led to an increased identification of aerococcal bacteremia. A. urinae remains the most common Aerococcus in blood cultures and in aerococcal IE. PMID- 26838687 TI - Discovering potential drug-targets for personalized treatment of autoimmune disorders - what we learn from epidermolysis bullosa acquisita. AB - INTRODUCTION: Epidermolysis bullosa acquisita (EBA) is a chronic autoimmune bullous dermatosis (AIBD). Treatment of EBA is challenging and mostly relies on systemic immunosuppression. During the last decade, intensive research led to the identification of new potential therapeutic targets that interfere in different phases of disease progression. Therapeutic interventions acting upon these candidate drug targets in animal models of EBA, such as cytokine-modulating biologics and small molecules, have validated them as potential new therapeutic strategies for EBA patients. AREAS COVERED: In this paper, we review the current treatments for EBA, describe the pathogenesis of the disease, and finally specify new drug candidates for the development of a more specific therapy with minimized side-effects for EBA and potentially other autoimmune diseases. EXPERT OPINION: We currently understand EBA as a disease that evolves from the interplay of many different signaling pathways. These signaling pathways, which are described in this review, provide new targets for EBA treatment. The ultimate goal of this research field is the development of specific, pathogenesis-based therapeutic strategies. Through identification of up- or downregulated pathways that dominate disease progression in individual patients, we expect therapy in EBA to become more and more precise and move towards a patient-based therapy. PMID- 26838686 TI - A novel inhibition ELISA for the detection and monitoring of Penicillium marneffei antigen in human serum. AB - The thermally dimorphic fungus Penicillium marneffei is a causative agent of penicilliosis marneffei, a disease considered to be an acquired immune deficiency syndrome (AIDS)-defining illness in Southeast Asia and southern China. We have developed an inhibition enzyme-linked immunosorbent assay (inh-ELISA) incorporating the yeast phase specific mannoprotein-binding monoclonal antibody 4D1 for the detection of P. marneffei infection. In our sample set, the test detected antigenemia in all 45 (100 %) patients with P. marneffei, with a mean antigen concentration of 4.32 MUg/ml. No cross-reactivity in this assay was found using serum from 44 additional patients with other fungal infections, such as Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans, as well as 44 patients with bacterial infections, such as Mycobacterium tuberculosis and Streptococcus suis. Additionally, no reactivity occurred using serum from 31 human immunodeficiency virus (HIV)-infected patients without a history of fungal infections and 113 healthy controls residing in endemic areas. To investigate the potential of the inh-ELISA for disease monitoring, we followed the reduction in antigenemia in six patients who clinically responded to itraconazole and P. marneffei was no longer isolated from their blood or tissues. In contrast, we correlated increased concentrations of antigenemia in patients with relapsed P. marneffei infection with the progression of their clinical symptoms and the isolation of P. marneffei from their clinical specimens. In summary, the P. marneffei inh-ELISA is a promising new assay for the rapid diagnosis of P. marneffei, as well as a tool for evaluating clinical response and clearance of the fungus during treatment. PMID- 26838688 TI - High plasma level of soluble RAGE is independently associated with a low recurrence of atrial fibrillation after catheter ablation in diabetic patient. AB - AIMS: Atrial fibrillation (AF) is closely associated with metabolic syndrome, and the receptor for advanced glycation end products (RAGE) pathway is involved in insulin resistance and cardiac remodelling. We hypothesized that plasma level of soluble RAGE (sRAGE) would predict clinical outcome after radiofrequency catheter ablation for AF. METHODS AND RESULTS: We measured pre-procedural plasma level of sRAGE in 496 patients who underwent AF ablation (142 patients with diabetes, 354 patients without diabetes selected by matching them with diabetic patients according to age, sex, and AF type). (i) Plasma level of sRAGE was significantly higher in diabetic patients than in non-diabetics (580.0 +/- 576.4 vs. 435.8 +/- 280.7 pg/mL, P = 0.005), but there was no difference in sRAGE levels between patients with clinical recurrence of AF and those without. (ii) During 24.5 +/- 18.0 months of follow-up, the recurrence of AF was significantly lower in the diabetic patient group with high sRAGE (>=418 pg/mL based on the median value) than the diabetic patient group with low sRAGE (log-rank P = 0.045). This was especially pronounced in patients with paroxysmal AF and diabetes (log-rank P = 0.016), but no association was found in non-diabetics. (iii) In multivariate Cox regression analysis, high sRAGE (HR 0.395, 95% CI 0.175-0.894, P = 0.026) and paroxysmal AF (HR 0.387, 95% CI 0.179-0.835, P = 0.016) were independently associated with the favourable clinical outcome of rhythm control after AF ablation in diabetic patients. CONCLUSION: High plasma level of sRAGE was independently associated with low AF recurrence after catheter ablation in diabetic patients, especially those with paroxysmal AF. PMID- 26838689 TI - Who is the operator, that is the question: a multicentre study of catheter ablation of atrial fibrillation. AB - AIMS: A worldwide survey reported that the success rate of atrial fibrillation (AF) ablation was higher in high-volume centers compared with low-volume centers. We tested whether the procedure volume of each operator was associated with the outcome of AF ablation in high-volume centres. METHODS AND RESULTS: We studied 471 patients with paroxysmal AF who underwent pulmonary vein (PV) isolation for the first time in three cardiovascular centers where the annual AF ablation volume was >100 procedures. We classified a total of 10 primary operators according to their operation volume on the basis of ACC/AHA/ACP CLINICAL COMPETENCE STATEMENT; high-volume operator (>=50 cases/year, N = 3) or low-volume operator (<50 cases/year, N = 7). The patients included were dichotomized according to the annual operation volume of their attending physician. The endpoints were the freedom from AF recurrence 1 year after the ablation, major complications including thromboembolisms, massive bleeding or death, and the procedural duration. RESULTS: A complete isolation of the four PVs was achieved in 99.1%. The freedom from AF recurrence was more common in patients treated by high-volume operators than those treated by low-volume operators (165/216 [76.4%] vs. 160/255 [62.8%]; P = 0.001). A high-volume operator was the only independent predictor of the freedom from AF recurrence (hazard ratio 1.73, 95% confidence interval 1.23-2.48; P = 0.002). The patients treated by high-volume operators were less likely to have major complications (1.4% vs. 7.8%; P = 0.001), and had a shorter procedural duration (139.9 +/- 25.3 vs. 149.3 +/- 27.1 min; P = 0.03). CONCLUSIONS: Operator proficiency may predict the outcome after AF ablation even in high-volume centres. PMID- 26838692 TI - Cardiac magnetic resonance imaging after ventricular tachyarrhythmias increases diagnostic precision and reduces the need for family screening for inherited cardiac disease. AB - AIMS: Guidelines recommend evaluation of family members of sudden cardiac death victims. However, initiation of cascade screening in families with uncertain diagnoses is not cost-effective and may cause unnecessary concern. For these reasons, we set out to assess to what extent cardiac magnetic resonance imaging (CMR) would increase the diagnostic precision and thereby possibly change the indication for family screening in patients with ventricular tachyarrhythmias. METHODS AND RESULTS: We retrospectively collected data from 79 patients hospitalized with aborted cardiac arrest (resuscitated from a cardiac arrest), ventricular tachycardia (VT), or syncope who underwent a CMR at the Copenhagen University Hospital, Rigshospitalet, Denmark. Besides CMR, the patients were evaluated with an electrocardiogram, echocardiogram (both 100%), coronary angiogram (CAG)/coronary computed tomography scan (CT-CAG) (81%), exercise stress test (47%), late potentials (54%), electrophysiological study (44%), pharmacological provocation (44%), and/or myocardial biopsy (16%). Family screening was indicated for 53 probands (67%) prior to CMR. After full workup, only 43 cases (54%) warranted evaluation of relatives (19% decrease, P = 0.034). The full evaluation changed whether family screening was indicated in 18 probands (14/18 moved to no indication for family screening). In the 18 where recommendations on family screening changed, CMR findings were the major driver for re-classification in 17 cases. CONCLUSION: Cardiac magnetic resonance imaging re-defines the cardiac diagnoses in a significant proportion of cases and reduces the number of patients in whom family screening is warranted. Cardiac magnetic resonance imaging is highly relevant for optimal care and resource allocation when an inherited heart disease is the presumed cause of life-threatening arrhythmias. PMID- 26838691 TI - Cost effectiveness of left atrial appendage closure with the Watchman device for atrial fibrillation patients with absolute contraindications to warfarin. AB - AIMS: Atrial fibrillation (AF) patients with contraindications to oral anticoagulation have had few options for stroke prevention. Recently, a novel oral anticoagulant, apixaban, and percutaneous left atrial appendage closure (LAAC) have emerged as safe and effective therapies for stroke risk reduction in these patients. This analysis assessed the cost effectiveness of LAAC with the Watchman device relative to apixaban and aspirin therapy in patients with non valvular AF and contraindications to warfarin therapy. METHODS AND RESULTS: A cost-effectiveness model was constructed using data from three studies on stroke prevention in patients with contraindications: the ASAP study evaluating the Watchman device, the ACTIVE A trial of aspirin and clopidogrel, and the AVERROES trial evaluating apixaban. The cost-effectiveness analysis was conducted from a German healthcare payer perspective over a 20-year time horizon. Left atrial appendage closure yielded more quality-adjusted life years (QALYs) than aspirin and apixaban by 2 and 4 years, respectively. At 5 years, LAAC was cost effective compared with aspirin with an incremental cost-effectiveness ratio (ICER) of ?16 971. Left atrial appendage closure was cost effective compared with apixaban at 7 years with an ICER of ?9040. Left atrial appendage closure was cost saving and more effective than aspirin and apixaban at 8 years and remained so throughout the 20-year time horizon. CONCLUSIONS: This analysis demonstrates that LAAC with the Watchman device is a cost-effective and cost-saving solution for stroke risk reduction in patients with non-valvular AF who are at risk for stroke but have contraindications to warfarin. PMID- 26838693 TI - Atrial fibrillation and risk of stroke: a nationwide cohort study. AB - AIM: Although the relation between stroke risk factors and stroke in patients with atrial fibrillation (AF) has been extensively examined, only few studies have explored the association of AF and the risk of ischaemic stroke/systemic thromboembolism/transient ischaemic attack (stroke/TE/TIA) in the presence of concomitant stroke risk factors. METHODS AND RESULTS: From nationwide registries, all persons who turned 50, 60, 70, or 80 from 1997 to 2011 were identified. Persons receiving warfarin were excluded. The absolute risk of stroke/TE/TIA was reported for a 5-year period, as was the absolute risk ratios for AF vs. no AF according to prior stroke and the number of additional risk factors. The study cohort comprised of 3 076 355 persons without AF and 48 189 with AF. For men aged 50 years, with no risk factors, the 5-year risk of stroke was 1.1% (95% confidence interval 1.1-1.1); with AF alone 2.5% (1.8-3.2); with one risk factor and no prior stroke or AF 2.5% (2.3-2.7); and with one factor, no prior stroke and AF 2.9% (1.4-4.3). In men aged 50 years with prior stroke as the only risk factor, 5-year risk was 10.2% (9.1-11.3). In men aged 70 years, the corresponding risks were 4.8% (4.7-4.9), 6.8% (5.7-7.9), 6.6% (6.3-6.8), 8.7 (7.4-9.9), and 19.1% (18.1-20.1), respectively. In women aged 50 years, the risk was of 0.7% (0.7-0.7), 2.1% (0.9-3.2), 1.6% (1.4-1.8), 4.1% (0.6-7.6), and 7.2% (6.3-8.2), respectively, and in women aged 70 years 3.4% (3.3-3.5), 8.2% (7.0-9.5), 4.6% (4.4-4.8), 9.1% (7.5-10.6), and 15.4% (14.5-16.4), respectively. CONCLUSIONS: Stroke/TE/TIA risk was particularly increased when prior stroke/TE/TIA was present. Atrial fibrillation is associated with an increase in risk of stroke/TE/TIA in the absence of other risk factors but only a moderate increase in risk when other risk factors are present. PMID- 26838694 TI - Five-year efficacy of pulmonary vein antrum isolation as a primary ablation strategy for atrial fibrillation: a single-centre cohort study. AB - AIMS: Pulmonary vein antrum isolation (PVAI) is the cornerstone of atrial fibrillation (AF) ablation. There is an ongoing discussion on whether and when to add substrate modification to PVAI. This study evaluates (1) long-term efficacy of PVAI as a primary ablation strategy in all patients independently from AF type and (2) predictors of arrhythmia recurrence. METHODS AND RESULTS: A total of 509 consecutive patients (mean age 57 years, 38.9% non-paroxysmal AF) with AF underwent PVAI. In redo procedures, ablation was restricted to re-pulmonary vein (PV) isolation in case of PV reconnection. If the PVs were found to be isolated, substrate modification was performed. In total, 774 procedures were performed. Mean follow-up duration after the first and last ablation was, respectively, 66 +/- 23 and 55 +/- 25 months. A single PVAI was sufficient in restoring and maintaining long-term sinus rhythm in 41.3% (n = 210) of patients. Multiple procedures (mean 1.5) with re-PV isolation increased long-term success to 58.3% (n = 297). Additional substrate modification (n = 70) increased success to 62.5% (n = 318). After the last ablation, 87.5% of patients experienced success or significant clinical improvement on or off antiarrhythmic drugs. The incidence of left-sided atrial flutter or atrial tachycardia was 5% after PVAI and increased to 32% after additional substrate modification. Independent predictors for arrhythmia recurrence after the last ablation were non-paroxysmal AF, female sex, body mass index, hypertension, and AF duration. CONCLUSION: Five-year freedom of atrial tachyarrhythmia could be achieved by PVAI as primary ablation strategy in 58.3% of patients. Additional substrate modification only moderately increased overall success. PMID- 26838696 TI - Treatment of von Willebrand Disease. AB - Congenital von Willebrand disease (VWD) and acquired von Willebrand syndrome (AVWS) reflect conditions caused by von Willebrand factor (VWF) deficiency and/or defects. VWD is the most common inherited bleeding disorder and AVWS arises from a variety of causes. Since VWF stabilizes and protects factor VIII (FVIII) in the circulation, this is also reduced in many patients with VWD. The treatment of VWD and AVWS therefore primarily entails replacement of VWF, and sometimes FVIII, to protect against bleeding. This may entail the use of VWF concentrates (currently plasma-derived) and/or FVIII concentrates (currently plasma-derived or more increasingly recombinant forms), and/or desmopressin to release endogenous VWF in subgroups of patients. For AVWS additional treatment of the underlying condition is also required. Adjunct therapies include antifibrinolytics. Globally, various formulations exist for both VWF and FVIII concentrates and are differentially available based on manufacturer marketing or regulatory approvals/clearances in different geographies. Also, guidelines for treatment of VWD vary for different localities and recombinant VWF is undergoing clinical trials. The current review provides an overview of the treatment of VWD as currently practiced in developed countries, and also provides a glimpse towards the future. PMID- 26838695 TI - Plasma-assisted quadruple-channel optosensing of proteins and cells with Mn-doped ZnS quantum dots. AB - Information extraction from nano-bio-systems is crucial for understanding their inner molecular level interactions and can help in the development of multidimensional/multimodal sensing devices to realize novel or expanded functionalities. The intrinsic fluorescence (IF) of proteins has long been considered as an effective tool for studying protein structures and dynamics, but not for protein recognition analysis partially because it generally contributes to the fluorescence background in bioanalysis. Here we explored the use of IF as the fourth channel optical input for a multidimensional optosensing device, together with the triple-channel optical output of Mn-doped ZnS QDs (fluorescence from ZnS host, phosphorescence from Mn(2+) dopant, and Rayleigh light scattering from the QDs), to dramatically improve the protein recognition and discrimination resolution. To further increase the cross-reactivity of the multidimensional optosensing device, plasma modification of proteins was explored to enhance the IF difference as well as their interactions with Mn-doped ZnS QDs. Such a sensor device was demonstrated for highly discriminative and precise identification of proteins in human serum and urine samples, and for cancer and normal cells as well. PMID- 26838697 TI - Thrombotic Risks in Red Blood Cell Transfusions. AB - Red blood cells play a key role in normal hemostasis and thrombosis. Their ability to affect coagulation is multifactorial and depends on their mechanical properties affecting viscosity and blood flow, ability to aggregate and adhere to each other and potentially to vascular endothelium, molecular signaling via microvesicles and surface proteins, including blood group antigens, and participation in nitric oxide metabolism. Transfused red blood cells suffer from a storage lesion that damages the cells leading to changes in shape, function, and intracellular communication. In this article, we review if and how transfused red blood cells may lead to both increased hemorrhage and increased thrombosis. PMID- 26838698 TI - The Judicious Use of Recombinant Factor VIIa. AB - Recombinant activated factor VIIa (rFVIIa) is a prohemostatic agent initially approved for use in hemophilia patients with inhibitors and recently for Glanzmann thrombasthenia. Despite its approval indications, rFVIIa has also been used for a diverse range of off-label indications to treat bleeding related to traumatic injury, major hemorrhage following surgery, intracranial hemorrhage, and for uncontrolled bleeding as a prothrombotic hemostatic agent. Despite its off-label use, the benefit of rFVIIa in most nonhemophilia settings remains uncertain as the majority of clinical trials have not consistently demonstrated beneficial effects as determined by reduced bleeding, decreased blood product utilization, or have not demonstrated a mortality benefit. As with any prohemostatic agent, the risk of thromboembolic events is increased when rFVIIa is used off-label. Pooled data from randomized nonhemophilia studies report an increased risk in the elderly for arterial thromboses, although most individual trials have been underpowered to determine adverse thrombotic events. The causes of thrombotic adverse events associated with off-label use of rFVIIa may be due to an increased risk of adverse events due to critical illness or due to higher doses of rFVIIa used in off-label trials. Without clearly supportive data, physicians should consider risk versus benefit and exercise restraint using rFVIIa in off-label settings. Further, evidence-based guidelines should be developed by professional organizations, and additional randomized controlled clinical trials are needed to further assess the efficacy and safety of off-label rFVIIa use. PMID- 26838699 TI - Safety of Salvaged Blood and Risk of Coagulopathy in Cardiac Surgery. AB - Cardiac surgery patients are prone to anemia from several mechanisms: intraoperative blood loss, preexisting anemia, and hemodilution. Patients are very frequently transfused with allogeneic red blood cells (RBC), which in itself is associated with harm. The use of RBC salvage technology has been advocated to salvage blood lost in the operative field and to reduce the need of homologous blood transfusion. Direct cardiotomy suction from the surgical field and unprocessed blood retransfusion is a common practice during cardiopulmonary bypass, but which is associated with a powerful activation of the coagulation and inflammatory systems: thrombin generation, excessive fibrinolysis, and release of proinflammatory cytokines. Compared with direct cardiotomy suction, the use of RBC salvage technology is able to reduce the amount of microparticles and activated proteins of autologous blood before retransfusion. However, when compared with no retransfusion of blood from the operative field, processed blood also triggers coagulopathy and inflammation. Clinical studies are discordant regarding the benefit of RBC salvage use during and after cardiac operations. Meta-analysis suggests reduced need of homologous blood transfusion, but no effects on mortality and morbidity. PMID- 26838700 TI - Gross Examination of the Placenta. AB - Gross examination of the placenta is important to identify lesions and prepare material for histologic sectioning. The umbilical cord shows many variations, some of which may be associated with significant perinatal morbidity and mortality. Membranous processes often relate to ascending infection, passage of meconium, or hemorrhage. Many villous lesions are the result of processes in the maternal or fetal circulation. Infarcts are common but need to be carefully identified on gross examination. Although certain routine histologic sections should be done on all placentas, the gross examination guides the selection and reveals other important aspects of the placenta to evaluate. PMID- 26838701 TI - Monozygotic Twinning. AB - This article discusses pathologies found in monozygotic twinning. Detailed information is provided regarding the development during monozygotic twin formation: embryo development, twin-to-twin transfusion syndrome, acardiac twinning, vanishing twins, conjoined twins, and Beckwith-Weidmann syndrome twins. An algorithm describing the approach for identifying pathology in a placenta with multiple pregnancies is presented. PMID- 26838702 TI - Ascending Infection: Acute Chorioamnionitis. AB - Acute chorioamnionitis is a major cause of spontaneous preterm birth, accounting for more than 40% of deliveries complicated by preterm premature rupture of membranes or preterm labor. In the majority of cases, especially in preterm births, acute chorioamnionitis is caused by ascending polymicrobial infection. Recent evidence suggests that in some cases acute chorioamnionitis may have a noninfectious cause. In addition to the nonspecific patterns of conventional acute chorioamnionitis, this article describes characteristic inflammatory patterns indicative of a specific infectious cause. Several inflammatory entities of putative immunologic (noninfectious) etiology are addressed, including eosinophilic/T-cell vasculitis and chronic chorioamnionitis. PMID- 26838703 TI - Umbilical Cord Pathology. AB - Problems and abnormalities of the umbilical cord play a significant role in perinatal morbidity and mortality. Because the umbilical cord is the lifeline of the fetus, any disruption of blood flow through the umbilical vessels can lead to severe fetal consequences. PMID- 26838704 TI - Fetal Thrombotic Vasculopathy: Perinatal Stroke, Growth Restriction, and Other Sequelae. AB - Clots in the fetal circulation of the placenta may occlude or narrow the lumens of fetal vessels sufficiently to diminish the placental oxygen and nutritional exchange, causing significant reduction in placental function. When extensive, growth restriction, neonatal encephalopathy, and stillbirth may occur. Propagation of clots in other organs, such as brain, kidney, and liver, may affect the function of these organs, resulting in infarcts and neonatal stroke. This article presents an account of the placental pathology and clinical sequelae of this condition, called fetal thrombotic vasculopathy. PMID- 26838705 TI - Maternal Floor Infarction and Massive Perivillous Fibrin Deposition. AB - Maternal floor infarction (MFI) and massive perivillous fibrin deposition (MPVFD) are pathologically overlapping placental disorders with characteristic gross and shared light microscopic features of excessive perivillous deposition of fibrinoid material. Although rare, they are associated with high rates of fetal growth restriction, perinatal morbidity and mortality, and risks of recurrence with fetal death. The cause of the extensive fibrinoid deposition is unknown, but evidence supports involvement of maternal alloimmune or autoimmune mechanisms. This article presents an updated discussion of features, placental histopathologic differential diagnosis, possible causes, clinical correlates, and adverse outcomes of the MFI/MPVFD spectrum. PMID- 26838706 TI - Villitis of Unknown Etiology and Massive Chronic Intervillositis. AB - Villitis of unknown etiology (VUE) is a common lesion affecting from 6.6% to 33.8% of third-trimester placentas. VUE needs to be distinguished from villitis of infectious etiology, most commonly cytomegalovirus and syphilis. Clinically, this lesion is associated with intrauterine growth retardation, intrauterine fetal demise, fetal neural impairment, maternal alloimmune and autoimmune disease, and maternal hypertension. It has a tendency to recur in subsequent pregnancies. Massive chronic intervillositis (MCI), also known as chronic histiocytic intervillositis, is a rare lesion that has an unclear relationship with VUE. MCI is associated with recurrent abortions. PMID- 26838707 TI - Placental Mesenchymal Dysplasia. AB - Placental mesenchymal dysplasia is a rare, incompletely understood placental stromal lesion, characterized by placentomegaly and striking ectasia and tortuosity of chorionic plate and stem villous vessels. Its prenatal ultrasonographic and gross pathologic features resemble those of a partial mole, but the fetus is typically normal and the placenta has a diploid, chromosomal complement. We discuss the pathologic features and current understanding of the etiopathogenesis of this condition, the supportive immunohistochemical and confirmatory molecular genetic studies important in its diagnosis, and its implications for pregnancy and infant outcomes. PMID- 26838708 TI - Correlation of Placental Pathology with Perinatal Brain Injury. AB - The purpose of placental pathology is to explain adverse clinical outcomes. One of the most tragic of these outcomes is perinatal brain injury with subsequent neurodisability. Findings in the placenta can play an important role in documenting sentinel events, uncovering clinically silent thromboinflammatory disease processes, revealing developmental alterations in functional reserve, and suggesting alterations in related maternal and fetal physiology. These findings, when integrated with clinical data, provide a plausible explanation for an otherwise unexpected outcome and can be helpful for treating physicians and family members. PMID- 26838709 TI - Placenta Accreta and Percreta. AB - The incidence of abnormally adherent placenta (accreta/percreta) has increased 10 fold in the past 50 years, predominantly due to the increased use of cesarean section delivery. The causes, clinical correlates, and pathology of these conditions are discussed in this article. PMID- 26838710 TI - Placental and Perinatal Pathology. PMID- 26838711 TI - BMA defends decision to end GPs' responsibility for care home residents. PMID- 26838712 TI - Critical Issues and Controversies in the Management of Patients With Carotid Artery Stenosis. PMID- 26838713 TI - Isolated dystypia after subthalamic nucleus deep brain stimulation in a patient with Parkinson's disease. PMID- 26838714 TI - Multidrug-resistant bacteria in unaccompanied refugee minors arriving in Frankfurt am Main, Germany, October to November 2015. AB - Many refugees arriving in Germany originate or have travelled through countries with high prevalence of multidrug-resistant Gram-negative organisms. Therefore, all unaccompanied refugee minors (<18 years-old) arriving in Frankfurt am Main between 12 October and 6 November 2015, were screened for multidrug-resistant Enterobacteriaceae in stool samples. Enterobacteriaceae with extended spectrum beta-lactamases (ESBL) were detected in 42 of 119 (35%) individuals, including nine with additional resistance to fluoroquinolones (8% of total screened), thus exceeding the prevalences in the German population by far. PMID- 26838715 TI - A new epidioxy-tetracyclic triterpenoid from Poria cocos Wolf. AB - A new epidioxy-tetracyclic triterpenoid, 3-(2-hydroxyacetoxy)-5alpha, 8alpha peroxydehydrotumulosic acid (10), along with nine known compounds were isolated from Poria cocos Wolf (Polyporaceae). Their structures were determined by extensive spectroscopic analyses and comparison with literature data. The cytotoxicity of these compounds against human cancer cell lines MNK-45 was evaluated by MTT method. PMID- 26838716 TI - Unraveling the Molecular Mechanisms Underlying the Nasopharyngeal Bacterial Community Structure. AB - The upper respiratory tract is colonized by a diverse array of commensal bacteria that harbor potential pathogens, such as Streptococcus pneumoniae. As long as the local microbial ecosystem-also called "microbiome"-is in balance, these potentially pathogenic bacterial residents cause no harm to the host. However, similar to macrobiological ecosystems, when the bacterial community structure gets perturbed, potential pathogens can overtake the niche and cause mild to severe infections. Recent studies using next-generation sequencing show that S. pneumoniae, as well as other potential pathogens, might be kept at bay by certain commensal bacteria, including Corynebacterium and Dolosigranulum spp. Bomar and colleagues are the first to explore a specific biological mechanism contributing to the antagonistic interaction between Corynebacterium accolens and S. pneumoniae in vitro [L. Bomar, S. D. Brugger, B. H. Yost, S. S. Davies, K. P. Lemon, mBio 7(1):e01725-15, 2016, doi:10.1128/mBio.01725-15]. The authors comprehensively show that C. accolens is capable of hydrolyzing host triacylglycerols into free fatty acids, which display antipneumococcal properties, suggesting that these bacteria might contribute to the containment of pneumococcus. This work exemplifies how molecular epidemiological findings can lay the foundation for mechanistic studies to elucidate the host-microbe and microbial interspecies interactions underlying the bacterial community structure. Next, translation of these results to an in vivo setting seems necessary to unveil the magnitude and importance of the observed effect in its natural, polymicrobial setting. PMID- 26838718 TI - Author Correction for Hochman et al., Fatal Pediatric Cerebral Malaria Is Associated with Intravascular Monocytes and Platelets That Are Increased with HIV Coinfection. PMID- 26838717 TI - Reconstruction of the Evolutionary History and Dispersal of Usutu Virus, a Neglected Emerging Arbovirus in Europe and Africa. AB - Usutu virus (USUV), one of the most neglected Old World encephalitic flaviviruses, causes epizootics among wild and captive birds and sporadic infection in humans. The dynamics of USUV spread and evolution in its natural hosts are unknown. Here, we present the phylogeny and evolutionary history of all available USUV strains, including 77 newly sequenced complete genomes from a variety of host species at a temporal and spatial scaled resolution. The results showed that USUV can be classified into six distinct lineages and that the most recent common ancestor of the recent European epizootics emerged in Africa at least 500 years ago. We demonstrated that USUV was introduced regularly from Africa into Europe in the last 50 years, and the genetic diversity of European lineages is shaped primarily by in situ evolution, while the African lineages have been driven by extensive gene flow. Most of the amino acid changes are deleterious polymorphisms removed by purifying selection, with adaptive evolution restricted to the NS5 gene and several others evolving under episodic directional selection, indicating that the ecological or immunological factors were mostly the key determinants of USUV dispersal and outbreaks. Host-specific mutations have been detected, while the host transition analysis identified mosquitoes as the most likely origin of the common ancestor and birds as the source of the recent European USUV lineages. Our results suggest that the major migratory bird flyways could predict the continental and intercontinental dispersal patterns of USUV and that migratory birds might act as potential long-distance dispersal vehicles. IMPORTANCE: Usutu virus (USUV), a mosquito-borne flavivirus of the Japanese encephalitis virus antigenic group, caused massive bird die-offs, mostly in Europe. There is increasing evidence that USUV appears to be pathogenic for humans, becoming a potential public health problem. The emergence of USUV in Europe allows us to understand how an arbovirus spreads, adapts, and evolves in a naive environment. Thus, understanding the epidemiological and evolutionary processes that contribute to the emergence, maintenance, and further spread of viral diseases is the sine qua non to develop and implement surveillance strategies for their control. In this work, we performed an expansive phylogeographic and evolutionary analysis of USUV using all published sequences and those generated during this study. Subsequently, we described the genetic traits, reconstructed the potential pattern of geographic spread between continents/countries of the identified viral lineages and the drivers of viral migration, and traced the origin of outbreaks and transition events between different hosts. PMID- 26838719 TI - Toxoplasma gondii Arginine Methyltransferase 1 (PRMT1) Is Necessary for Centrosome Dynamics during Tachyzoite Cell Division. AB - The arginine methyltransferase family (PRMT) has been implicated in a variety of cellular processes, including signal transduction, epigenetic regulation, and DNA repair pathways. PRMT1 is thought to be responsible for the majority of PRMT activity in Toxoplasma gondii, but its exact function is unknown. To further define the biological function of the PRMT family, we generated T. gondii mutants lacking PRMT1 (Deltaprmt1) by deletion of the PRMT1 gene. Deltaprmt1 parasites exhibit morphological defects during cell division and grow slowly, and this phenotype reverses in the Deltaprmt::PRMT1mRFP complemented strain. Tagged PRMT1 localizes primarily in the cytoplasm with enrichment at the pericentriolar material, and the strain lacking PRMT1 is unable to segregate progeny accurately. Unlike wild-type and complemented parasites, Deltaprmt1 parasites have abnormal daughter buds, perturbed centrosome stoichiometry, and loss of synchronous replication. Whole-genome expression profiling demonstrated differences in expression of cell-cycle-regulated genes in the Deltaprmt1 strain relative to the complemented Deltaprmt1::PRMT1mRFP and parental wild-type strains, but these changes do not correlate with a specific block in cell cycle. Although PRMT1's primary biological function was previously proposed to be methylation of histones, our studies suggest that PRMT1 plays an important role within the centrosome to ensure the proper replication of the parasite. IMPORTANCE: Apicomplexan parasites include several important pathogens, including Toxoplasma gondii, a major cause of opportunistic infections and congenital birth defects. These parasites divide using a unique form of cell division called endodyogeny that is different from those of most eukaryotes. PRMT1 is a conserved arginine methyltransferase that was thought to regulate gene expression of T. gondii by modifying histone methylation. Using genetic techniques, we show that disruption of PRMT1 affects the parasite's ability to perform accurate cell division. Our studies reveal an unexpected role for arginine methylation in centrosome biology and regulation of parasite replication. PMID- 26838721 TI - Will Regulatory and Financial Considerations Dampen Innovation in the Clinical Microbiology Laboratory? AB - Over a million prosthetic joints are placed in patients in the United States annually. Of those that fail, 25% will be due to infection, with an estimated cost approaching 1 billion dollars. Despite the clinical and economic importance of these infections, the techniques for their detection are relatively insensitive. An innovative method for detecting these infections by using blood culture bottles (BCB) to culture specimens of periprosthetic tissue (PPT) was described in a recent article [T. N. Peel, et al., mBio 7(1):e01776-15, 2016, doi:10.1128/mBio.01776-15]. There are two potential stumbling blocks to the widespread implementation of this innovation. First, the FDA judges such an application of BCB as an "off-label use" and as such, a laboratory-developed test (LDT). LDTs are coming under greater scrutiny by the FDA and may require extensive, costly validation studies in laboratories that adopt this methodology. Second, the Center for Medicare and Medicaid Services has established a Hospital Acquired Condition Reduction Act under which institutions performing in the lowest quartile forfeit 1% of their Medicare reimbursement. Hospital-acquired infections are an important component of this quality metric. Although prosthetic joint infection (PJI) rates are not currently a hospital quality metric, given their cost and increasing frequency, it is reasonable to expect that they may become one. Will those with financial oversight allow an innovative technique that will require an expensive validation and may put the institution at risk for loss of CMS reimbursement? PMID- 26838720 TI - Two Modes of the Axonal Interferon Response Limit Alphaherpesvirus Neuroinvasion. AB - Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at epithelial surfaces and continues into the peripheral nervous system (PNS). Inflammatory responses are induced at the infected peripheral site prior to invasion of the PNS. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which includes the interferons (IFNs). The fundamental question is how do PNS cell bodies respond to these distant, potentially damaging events experienced by axons. Using compartmented cultures that physically separate neuron axons from cell bodies, we found that pretreating isolated axons with beta interferon (IFN-beta) or gamma interferon (IFN-gamma) significantly diminished the number of herpes simplex virus 1 (HSV-1) and PRV particles moving in axons toward the cell bodies in a receptor-dependent manner. Exposing axons to IFN-beta induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFN-gamma induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated antiviral effects induced by IFN gamma, but not those induced by IFN-beta. Proteomic analysis of IFN-beta- or IFN gamma-treated axons identified several differentially regulated proteins. Therefore, unlike treatment with IFN-gamma, IFN-beta induces a noncanonical, local antiviral response in axons. The activation of a local IFN response in axons represents a new paradigm for cytokine control of neuroinvasion. IMPORTANCE: Neurons are highly polarized cells with long axonal processes that connect to distant targets. PNS axons that innervate peripheral tissues are exposed to various situations that follow infection, inflammation, and damage of the tissue. After viral infection in the periphery, axons represent potential front-line barriers to PNS infection and damage. Indeed, most viral infections do not spread to the PNS, yet the mechanisms responsible are not well studied. We devised an experimental system to study how axons respond to inflammatory cytokines that would be produced by infected tissues. We found that axons respond differentially to type I and type II interferons. The response to type I interferon (IFN-beta) is a rapid axon-only response. The response to type II interferon (IFN-gamma) involves long-distance signaling to the PNS cell body. These responses to two interferons erect an efficient and rapid barrier to PNS infection. PMID- 26838722 TI - The NADase-Negative Variant of the Streptococcus pyogenes Toxin NAD+ Glycohydrolase Induces JNK1-Mediated Programmed Cellular Necrosis. AB - Virulence factors are often multifunctional and contribute to pathogenesis through synergistic mechanisms. For the human pathogen Streptococcus pyogenes, two factors that act synergistically are the S. pyogenes NAD(+) glycohydrolase (SPN) and streptolysin O (SLO). Through distinct mechanisms, SLO forms pores in host cell membranes and translocates SPN into the host cell cytosol. Two natural variants of SPN exist, one that exhibits NADase activity and one that lacks this function, and both versions are translocated and act in concert with SLO to cause an accelerated death response in epithelial cells. While NADase(+) SPN is known to trigger a metabolic form of necrosis through the depletion of NAD(+), the mechanism by which NADase(-) SPN induces cell death was unknown. In the studies described here, we examined the pathway of NADase(-) cell death through analysis of activation patterns of mitogen-activated protein kinases (MAPKs). S. pyogenes infection resulted in activation of members of three MAPK subfamilies (p38, ERK, and JNK). However, only JNK was activated in an SLO-specific manner. NADase(-) SPN induced necrosis in HeLa epithelial cells associated with depolarization of mitochondrial membranes, activation of NF-kappaB, and the generation of reactive oxygen species. Remarkably, RNA interference (RNAi) silencing of JNK protected cells from NADase(-)-SPN-mediated necrosis, suggesting that NADase(-) SPN triggers a form of programmed necrosis dependent on JNK signaling. Taken together, these data demonstrate that SPN acts with SLO to elicit necrosis through two different mechanisms depending on its NADase activity, i.e., metabolic (NADase(+)) or programmed (NADase(-)), leading to distinct inflammatory profiles. IMPORTANCE: Many bacterial pathogens produce toxins that alter how infected host cells interact with the immune system. For Streptococcus pyogenes, two toxins, a NAD(+) glycohydrolase (SPN) and streptolysin O (SLO), act in combination to cause infected cells to die. However, there are two natural forms of SPN, and these variants cause dying cells to produce different types of signaling molecules. The NADase(+) form of SPN kills cells by depleting reserves of NAD(+) and cellular energy. The other form of SPN lacks this activity (NADase( )); thus, the mechanism by which this variant induces toxicity was unknown. Here, we show that infected cells recognize NADase(-) SPN through a specific signaling molecule called JNK, which causes these cells to undergo a form of cellular suicide known as programmed necrosis. This helps us to understand how different forms of toxins alter host cell signaling to help S. pyogenes cause different types of diseases. PMID- 26838723 TI - Maternal Neutralization-Resistant Virus Variants Do Not Predict Infant HIV Infection Risk. AB - Mother-to-child transmission (MTCT) of HIV provides a setting for studying immune correlates of protection. Neutralizing antibodies (NAbs) are suggested to contribute to a viral bottleneck during MTCT, but their role in blocking transmission is unclear, as studies comparing the NAb sensitivities of maternal viruses have yielded disparate results. We sought to determine whether transmitting mothers differ from nontransmitting mothers in the ability to neutralize individual autologous virus variants present at transmission. Ten transmitting and 10 nontransmitting HIV-infected mothers at high risk of MTCT were included in this study. Full-length HIV envelope genes (n = 100) were cloned from peripheral blood mononuclear cells obtained near transmission from transmitting mothers and at similar time points from nontransmitting mothers. Envelope clones were tested as pseudoviruses against contemporaneous, autologous maternal plasma in neutralization assays. The association between transmission and the log2 50% inhibitory concentration (IC50) for multiple virus variants per mother was estimated by using logistic regression with clustered standard errors. t tests were used to compare proportions of neutralization-resistant viruses. Overall, transmitting mothers had a median IC50 of 317 (interquartile range [IQR], 202 to 521), and nontransmitting mothers had a median IC50 of 243 (IQR, 95 to 594). Transmission risk was not significantly associated with autologous NAb activity (odds ratio, 1.25; P = 0.3). Compared to nontransmitting mothers, transmitting mothers had similar numbers of or fewer neutralization-resistant virus variants, depending on the IC50 neutralization resistance cutoff. In conclusion, HIV-infected mothers harbor mostly neutralization-sensitive viruses, although resistant variants were detected in both transmitting and nontransmitting mothers. These results suggest that MTCT during the breastfeeding period is not driven solely by the presence of maternal neutralization escape variants. IMPORTANCE: There are limited data demonstrating whether NAbs can prevent HIV transmission and infection in humans, and for this reason, NAbs have been studied in MTCT, where maternal antibodies are present at the time of transmission. Results of these studies have varied, perhaps because of differences in methods. Importantly, studies often used cultured viruses and samples from time points outside the window of transmission, which could confound findings. Here, we considered the role of maternal NAbs against individual maternal virus variants near the time of transmission. We found no evidence that NAbs are associated with protection from infection. In fact, depending on the cutoff used to define neutralization resistance, we found evidence that nontransmitting mothers have more neutralization-resistant virus variants. These results suggest that lack of virus transmission in the early breastfeeding period is not simply due to an absence of maternal neutralization escape variants and likely includes multiple factors. PMID- 26838724 TI - A Novel Secreted Protein, MYR1, Is Central to Toxoplasma's Manipulation of Host Cells. AB - The intracellular protozoan Toxoplasma gondii dramatically reprograms the transcriptome of host cells it infects, including substantially up-regulating the host oncogene c-myc. By applying a flow cytometry-based selection to infected mouse cells expressing green fluorescent protein fused to c-Myc (c-Myc-GFP), we isolated mutant tachyzoites defective in this host c-Myc up-regulation. Whole genome sequencing of three such mutants led to the identification of MYR1 (Myc regulation 1; TGGT1_254470) as essential for c-Myc induction. MYR1 is a secreted protein that requires TgASP5 to be cleaved into two stable portions, both of which are ultimately found within the parasitophorous vacuole and at the parasitophorous vacuole membrane. Deletion of MYR1 revealed that in addition to its requirement for c-Myc up-regulation, the MYR1 protein is needed for the ability of Toxoplasma tachyzoites to modulate several other important host pathways, including those mediated by the dense granule effectors GRA16 and GRA24. This result, combined with its location at the parasitophorous vacuole membrane, suggested that MYR1 might be a component of the machinery that translocates Toxoplasma effectors from the parasitophorous vacuole into the host cytosol. Support for this possibility was obtained by showing that transit of GRA24 to the host nucleus is indeed MYR1-dependent. As predicted by this pleiotropic phenotype, parasites deficient in MYR1 were found to be severely attenuated in a mouse model of infection. We conclude, therefore, that MYR1 is a novel protein that plays a critical role in how Toxoplasma delivers effector proteins to the infected host cell and that this is crucial to virulence. IMPORTANCE: Toxoplasma gondii is an important human pathogen and a model for the study of intracellular parasitism. Infection of the host cell with Toxoplasma tachyzoites involves the introduction of protein effectors, including many that are initially secreted into the parasitophorous vacuole but must ultimately translocate to the host cell cytosol to function. The work reported here identified a novel protein that is required for this translocation. These results give new insight into a very unusual cell biology process as well as providing a potential handle on a pathway that is necessary for virulence and, therefore, a new potential target for chemotherapy. PMID- 26838725 TI - Preclinical Efficacy of Clumping Factor A in Prevention of Staphylococcus aureus Infection. AB - Treatment of Staphylococcus aureus infections has become increasingly difficult because of the emergence of multidrug-resistant isolates. Development of a vaccine to prevent staphylococcal infections remains a priority. To determine whether clumping factor A (ClfA) is a good target protein for inclusion in a multivalent vaccine, we evaluated its efficacy in a variety of relevant staphylococcal infection models, challenging with different S. aureus strains. ClfA adsorbed to Alhydrogel and mixed with Sigma Adjuvant System was more immunogenic and stimulated a more robust Th17 response than ClfA administered with alum alone. ClfA immunization induced the production of functional antibodies in rabbits and mice that blocked S. aureus binding to fibrinogen and were opsonic for S. aureus strains that produced little or no capsular polysaccharide. Mice immunized with ClfA showed a modest reduction in the bacterial burden recovered from subcutaneous abscesses provoked by S. aureus USA300 strain LAC. In addition, the ClfA vaccine reduced lethality in a sepsis model following challenge with strain Newman, but not ST80. Vaccination with ClfA did not protect against surgical wound infection, renal abscess formation, or bacteremia. Passive immunization with antibodies to ClfA did not protect against staphylococcal bacteremia in mice or catheter-induced endocarditis in rats. Some enhancement of bacteremia was observed by ClfA immunization or passive administration of ClfA antibodies when mice were challenged by the intraperitoneal route. Although rodent models of staphylococcal infection have their limitations, our data do not support the inclusion of ClfA in an S. aureus multivalent vaccine. IMPORTANCE: Antibiotics are often ineffective in eradicating Staphylococcus aureus infections, and thus, a preventative vaccine is sorely needed. Two single-component vaccines and two immunoglobulin preparations failed to meet their designated endpoints in phase III clinical trials. Importantly, recipients of an S. aureus surface protein (iron surface determinant B) vaccine who developed a staphylococcal infection experienced a higher rate of multiorgan failure and mortality than placebo controls, raising safety concerns. Multicomponent S. aureus vaccines have now been generated, and several include surface protein clumping factor A (ClfA). We immunized mice with ClfA and generated a robust T cell response and serum antibodies that were functional in vitro. Nonetheless, ClfA was not protective in a number of relevant animal models of S. aureus infection, and high levels of ClfA antibodies enhanced bacteremia when mice were challenged with community-acquired methicillin-resistant S. aureus strains. Evidence supporting ClfA as a vaccine component is lacking. PMID- 26838726 TI - Reduction of Streptococcus pneumoniae Colonization and Dissemination by a Nonopsonic Capsular Polysaccharide Antibody. AB - Streptococcus pneumoniae colonization of the nasopharynx (NP) is a prerequisite for invasive pneumococcal disease (IPD). The marked reduction in IPD that followed the routine use of pneumococcal polysaccharide conjugate vaccines (PCVs) has been linked to reduced NP colonization with vaccine-included serotypes (STs), with the caveat that PCVs are less effective against pneumonia than against IPD. Although PCV-elicited opsonic antibodies that enhance phagocytic killing of the homologous ST are considered a key correlate of PCV-mediated protection, recent studies question this relationship for some STs, including ST3. Studies with monoclonal antibodies (MAbs) to the pneumococcal capsular polysaccharide (PPS) of ST3 (PPS3) have shown that nonopsonic, as well as opsonic, antibodies can each protect mice against pneumonia and sepsis, but the effect of these types of MAbs on NP colonization is unknown. In this study, we determined the effects of protective opsonic and nonopsonic PPS3 MAbs on ST3 NP colonization in mice. Our results show that a nonopsonic MAb reduced early NP colonization and prevented ST3 dissemination to the lungs and blood, but an opsonic MAb did not. Moreover, the opsonic MAb induced a proinflammatory NP cytokine response, but the nonopsonic MAb had an antiinflammatory effect. The effect of the nonopsonic MAb on colonization did not require its Fc region, but its antiinflammatory effect did. Our findings challenge the paradigm that opsonic MAbs are required to prevent NP colonization and suggest that further studies of the activity of nonopsonic antibodies could advance our understanding of mechanisms of PCV efficacy and provide novel correlates of protection. IMPORTANCE: Pneumococcal conjugate vaccines (PCVs) have markedly reduced the incidence of invasive pneumococcal disease (IPD). Vaccine-elicited pneumococcal polysaccharide (PPS) antibodies that enhance in vitro phagocyte killing of vaccine-included serotypes (STs) (opsonic antibodies) have been considered correlates of vaccine protection and are thought to exert their effect at the initial site of infection, the nasopharynx (NP). However, the data presented here show that this is not the necessarily the case. A nonopsonic PPS monoclonal antibody (MAb) reduced pneumococcal colonization and dissemination of its homologous ST in mice, but surprisingly, an opsonic PPS MAb to the same ST did not. These results reveal that PPS antibodies can work in different ways than previously thought, challenge the paradigm that opsonic antibodies are required to prevent IPD, and provide new insights into PCV efficacy that could lead to novel correlates of vaccine protection. PMID- 26838728 TI - What Should Primary Care Providers Know About the Changes in DSM-5? AB - Primary care providers are increasingly involved in the management of patients with mental disorders, particularly as integrated models of care emerge. The recent publication of the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) represents a shift in the classification of several mental disorders commonly encountered by primary care providers. With the advent of ICD-10 and the movement toward diagnostic specificity, it is crucial that primary care providers understand the rationale behind these changes. This paper provides an overview of the changes in the classification of mental disorders in DSM-5, a description of how these changes relate to frequently used screening tools in the primary care setting, and a critique of how these changes will affect mental health practice from a primary care perspective. PMID- 26838729 TI - A Moderate Carnitine Deficiency Exacerbates Isoproterenol-Induced Myocardial Injury in Rats. AB - PURPOSE: The myocardium is largely dependent upon oxidation of fatty acids for the production of ATP. Cardiac contractile abnormalities and failure have been reported after acute emotional stress and there is evidence that catecholamines are responsible for acute stress-induced heart injury. We hypothesized that carnitine deficiency increases the risk of stress-induced heart injury. METHODS: Carnitine deficiency was induced in Wistar rats by adding 20 mmol/L of sodium pivalate to drinking water (P). Controls (C) received equimolar sodium bicarbonate and a third group (P + Cn) received pivalate along with 40 mmol/L carnitine. After 15 days, 6 rats/group were used to evaluate function of isolated hearts under infusion of 0.1 MUM isoproterenol and 20 rats/group were submitted to a single subcutaneous administration of 50 mg/kg isoproterenol. RESULTS: Isoproterenol infusion in C markedly increased the heart rate, left ventricular (LV) systolic pressure and coronary flow rate. In P rats, isoproterenol increased the heart rate and LV systolic pressure but these increases were not paralleled by a rise in the coronary flow rate and LV diastolic pressure progressively increased. Subcutaneous isoproterenol induced 15 % mortality rate in C and 50 % in P (p < 0.05). Hearts of surviving P rats examined 15 days later appeared clearly dilated, presented a marked impairment of LV function and a greater increase in tumor necrosis factor alpha (TNFalpha) levels. All these detrimental effects were negligible in P + Cn rats. CONCLUSIONS: Our study suggests that carnitine deficiency exposes the heart to a greater risk of injury when sympathetic nerve activity is greatly stimulated, for example during emotional, mental or physical stress. PMID- 26838730 TI - Optical properties of drug metabolites in latent fingermarks. AB - Drug metabolites usually have structures of split-ring resonators (SRRs), which might lead to negative permittivity and permeability in electromagnetic field. As a result, in the UV-vis region, the latent fingermarks images of drug addicts and non drug users are inverse. The optical properties of latent fingermarks are quite different between drug addicts and non-drug users. This is a technic superiority for crime scene investigation to distinguish them. In this paper, we calculate the permittivity and permeability of drug metabolites using tight binding model. The latent fingermarks of smokers and non-smokers are given as an example. PMID- 26838731 TI - Low lattice thermal conductivity of stanene. AB - A fundamental understanding of phonon transport in stanene is crucial to predict the thermal performance in potential stanene-based devices. By combining first principle calculation and phonon Boltzmann transport equation, we obtain the lattice thermal conductivity of stanene. A much lower thermal conductivity (11.6 W/mK) is observed in stanene, which indicates higher thermoelectric efficiency over other 2D materials. The contributions of acoustic and optical phonons to the lattice thermal conductivity are evaluated. Detailed analysis of phase space for three-phonon processes shows that phonon scattering channels LA + LA/TA/ZA <-> TA/ZA are restricted, leading to the dominant contributions of high-group velocity LA phonons to the thermal conductivity. The size dependence of thermal conductivity is investigated as well for the purpose of the design of thermoelectric nanostructures. PMID- 26838732 TI - beta3-adrenoceptor impacts apoptosis in cultured cardiomyocytes via activation of PI3K/Akt and p38MAPK. AB - beta3-adrenoceptor (beta3-AR) has been shown to promote myocardial apoptosis. However, the exact physiological role and importance of this receptor in the human myocardium, and its underlying mode of action, have not been fully elucidated. The present study aimed to determine the effects of beta3-AR on the promotion of myocardial apoptosis and on norepinephrine (NE) injury. We analyzed NE-induced cardiomyocyte (CM) apoptosis by using a TUNEL and an annexin V/propidium iodide apoptosis assay. Furthermore, we investigated the NE-induced expression of the apoptosis marker genes Akt and p38MAPK, their phosphorylated counterparts p-Akt and p-p38MAPK, caspase-3, Bcl-2, and Bax. In addition, we determined the effect of a 48-h treatment with a beta3-AR agonist and antagonist on expression of these marker genes. beta3-AR overexpression was found to increase CM apoptosis, accompanied by an increased expression of caspase-3, bax/bcl-2, and p-p38MAPK. In contrast, the beta3-blocker reduced apoptosis of CMs and the associated elevated Akt expression. We identified a novel and potent anti apoptosis mechanism via the PI3K/Akt pathway and a pro-apoptosis pathway mediated by p38MAPK. PMID- 26838733 TI - Tacrolimus inhibits vasoconstriction by increasing Ca(2+) sparks in rat aorta. AB - The present study attempted to test a novel hypothesis that Ca(2+) sparks play an important role in arterial relaxation induced by tacrolimus. Recorded with confocal laser scanning microscopy, tacrolimus (10 umol/L) increased the frequency of Ca(2+) sparks, which could be reversed by ryanodine (10 umol/L). Electrophysiological experiments revealed that tacrolimus (10 umol/L) increased the large-conductance Ca(2+)-activated K(+) currents (BKCa) in rat aortic vascular smooth muscle cells (AVSMCs), which could be blocked by ryanodine (10 umol/L). Furthermore, tacrolimus (10 and 50 umol/L) reduced the contractile force induced by norepinephrine (NE) or KCl in aortic vascular smooth muscle in a concentration-dependent manner, which could be also significantly attenuated by iberiotoxin (100 nmol/L) and ryanodine (10 umol/L) respectively. In conclusion, tacrolimus could indirectly activate BKCa currents by increasing Ca(2+) sparks released from ryanodine receptors, which inhibited the NE- or KCl-induced contraction in rat aorta. PMID- 26838734 TI - Multilayer Coating of Tetrandrine-loaded PLGA nanoparticles: Effect of surface charges on cellular uptake rate and drug release profile. AB - The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3+/ 5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery. PMID- 26838736 TI - ROCK inhibition with fasudil promotes early functional recovery of spinal cord injury in rats by enhancing microglia phagocytosis. AB - Emerging evidence indicates that microglia activation plays an important role in spinal cord injury (SCI) caused by trauma. Studies have found that inhibiting the Rho/Rho-associated protein kinase (ROCK) signaling pathway can reduce inflammatory cytokine production by microglia. In this study, Western blotting was conducted to detect ROCK2 expression after the SCI; the ROCK Activity Assay kit was used for assay of ROCK pathway activity; microglia morphology was examined using the CD11b antibody; electron microscopy was used to detect microglia phagocytosis; TUNEL was used to detect tissue cell apoptosis; myelin staining was performed using an antibody against myelin basic protein (MBP); behavioral outcomes were evaluated according to the methods of Basso, Beattie, and Bresnahan (BBB). We observed an increase in ROCK activity and microglial activation after SCI. The microglia became larger and rounder and contained myelin-like substances. Furthermore, treatment with fasudil inhibited neuronal cells apoptosis, alleviated demyelination and the formation of cavities, and improved motor recovery. The experimental evidence reveals that the ROCK inhibitor fasudil can regulate microglial activation, promote cell phagocytosis, and improve the SCI microenvironment to promote SCI repair. Thus, fasudil may be useful for the treatment of SCI. PMID- 26838735 TI - Neuroprotective effect of peptides extracted from walnut (Juglans Sigilata Dode) proteins on Abeta25-35-induced memory impairment in mice. AB - Alzheimer's disease (AD) is one of the major neurodegenerative disorders of the elderly, which is characterized by the accumulation and deposition of amyloid beta (Abeta) peptide in human brains. Oxidative stress and neuroinflammation induced by Abeta in brain are increasingly considered to be responsible for the pathogenesis of AD. The present study aimed to determine the protective effects of walnut peptides against the neurotoxicity induced by Abeta25-35 in vivo. Briefly, the AD model was induced by injecting Abeta25-35 into bilateral hippocampi of mice. The animals were treated with distilled water or walnut peptides (200, 400 and 800 mg/kg, p.o.) for five consecutive weeks. Spatial learning and memory abilities of mice were investigated by Morris water maze test and step-down avoidance test. To further explore the underlying mechanisms of the neuroprotectivity of walnut peptides, the activities of superoxide dismutase (SOD), glutathione (GSH), acetylcholine esterase (AChE), and the content of malondialdehyde (MDA) as well as the level of nitric oxide (NO) in the hippocampus of mice were measured by spectrophotometric method. In addition, the levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor-alpha (TNF alpha), interleukin 1beta (IL-1beta) and IL-6 in the samples were determined using ELISA. The hippocampal expressions of inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-kappaB) were evaluated by Western blot analysis. The results showed that walnut peptides supplementation effectively ameliorated the cognitive deficits and memory impairment of mice. Meanwhile, our study also revealed effective restoration of levels of antioxidant enzymes as well as inflammatory mediators with supplementation of walnut peptides (400 or 800 mg/kg). All the above findings suggested that walnut peptides may have a protective effect on AD by reducing inflammatory responses and modulating antioxidant system. PMID- 26838737 TI - Expression and clinical significance of IL-17 and IL-17 receptor in ulcerative colitis. AB - The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor (IL-17R) in intestinal mucosa tissue in patients with ulcerative colitis (UC) and controls, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein (CRP) levels were determined by ELISA and immunonephelometry, respectively. The IL-17R mRNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls (P<0.05). Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase (P<0.05), and correlated with CRP levels (r=0.578, P<0.01). IL-17R expression levels were higher in active UC patients than in healthy controls (P<0.05). It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients. PMID- 26838738 TI - Peroxisome proliferator-activated receptor-gamma agonist pioglitazone fails to attenuate renal fibrosis caused by unilateral ureteral obstruction in mice. AB - Renal tubulointerstitial fibrosis is the common ending of progressive renal disease. It is worth developing new ways to stop the progress of renal fibrosis. Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists have been studied to treat diabetic nephropathy, cisplatin-induced acute renal injury, ischemia reperfusion injury and adriamycin nephropathy. In this study, unilateral ureteral obstruction (UUO) was used to establish a different renal fibrosis model. PPAR? agonist pioglitazone was administrated by oral gavage and saline was used as control. At 7th and 14th day after the operation, mice were sacrificed for fibrosis test and T lymphocytes subsets test. Unexpectedly, through MASSON staining, immunohistochemistry for alpha-SMA, and Western blotting for a-SMA and PDGFR-beta, we found that pioglitazone failed to attenuate renal fibrosis in UUO mice. However, flow cytometry showed that pioglitazone down-regulated Th1 cells, and up-regulated Th2 cells, Th17 cells and Treg cells. But the Th17/Treg ratio had no significant change by pioglitazone. Real-time PCR results showed that TGF beta and MCP-1 had no significant changes, at the same time, CD4(+) T cells associated cytokines were partially regulated by pioglitazone pretreatment. Taken together, pioglitazone failed to suppress renal fibrosis progression caused by UUO. PMID- 26838739 TI - Biliverdin protects against cisplatin-induced apoptosis of renal tubular epithelial cells. AB - Biliverdin (BV) has long been thought to be a cytotoxic metabolic waste product. It has also been demonstrated to have important cytoprotective functions during oxidative stress. The present study aimed to examine the cytoprotective effect of BV on NRK-52E cells, a proximal tubular cell line derived from rat kidney. Cells were treated with 50 umol/L cisplatin for 24 h (cisplatin group) or pre-treated with BV for 30 min, then with 50 umol/L cisplatin for 24 h (cisplatin+BV group). Those given no treatment served as a control. Cell apoptosis was evaluated by flow cytometry and cell viability by Cell Counting Kit-8 (CCK-8). The protein expressions of cleaved caspase3, Bax and Bcl-2 were assessed by Western blotting. Reactive oxygen species (ROS) levels were measured using carboxydichlorodihydrofluorescein diacetate (H2DCF). The results showed that cisplatin induced the apoptosis of NRK-52E cells, decreased cell viability, and increased the formation of ROS by upregulating the expression of cleaved caspase3 and Bax and decreasing Bcl-2 protein expression. These effects could be significantly reversed by pretreatment with BV. It was concluded that BV can protect against cisplatin-induced cell apoptosis through the anti-oxidative effects. PMID- 26838740 TI - Correlation of liver enzymes with diabetes and pre-diabetes in middle-aged rural population in China. AB - The survey aimed to explore the association of liver transaminases with the prevalence of type 2 diabetes mellitus (T2DM) and pre-diabetes (pre-DM) in the middle-aged rural population in China. A cross-sectional study was conducted in 10 800 middle-aged subjects who lived in rural area of central China. The 75-g oral glucose-tolerance test (OGTT) was performed. Participants were asked to complete physical examination and standard questionnaire. The serum liver transaminases (ALT and GGT), HbA1C and serum lipids were measured. In middle-aged rural population, the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), impaired fasting glucose combined with impaired glucose tolerance (IFG+IGT) and DM was 4.0%, 11.8%, 2.6% and 10.0%, respectively. Some measurements were higher in males than in females, such as waist hip ratio (WHR), blood pressure, fasting blood glucose (FBG), high density lipoprotein-cholesterol (HDL-C), and liver enzymes (ALT and GGT). Further, we found that elevated serum GGT and ALT levels were significantly positively correlated with the prevalence of DM, independent of central obesity, serum lipid and insulin resistance (IR) in both genders. However, the correlation of GGT and ALT with pre-DM was determined by genders and characteristics of liver enzymes. Higher serum GGT was indicative of IGT in both genders. The association of serum ALT with pre-DM was significant only in female IGT group. In conclusion, our present survey shows both serum GGT and ALT are positively associated with DM, independent of the cardiovascular risk factors in both genders. PMID- 26838741 TI - Increased BMR in overweight and obese patients with type 2 diabetes may result from an increased fat-free mass. AB - The study aimed to determine the relationships between the basal metabolic rate (BMR) and body composition of overweight and obese Chinese adults with type 2 diabetes mellitus (DM). This cross-sectional clinical study enrolled 193 Chinese adults with type 2 DM who were overweight (24 kg/m(2)=BMI<=28 kg/m(2), n=99), or obese (BMI >=28 kg/m(2), n=94). Ninety-seven adults with normal BMIs, including 50 DM patients and 47 healthy adults, were recruited as a control group. BMR was measured by indirect calorimetry; predicted BMR was calculated according to the Schofield equation; and the relationships between BMR, body composition, and biochemical results were determined by the Pearson correlation. The results showed that obese DM patients had significantly higher BMRs than both overweight patients (P<0.05) and patients with normal BMI did (P<0.05). The measured BMR was significantly lower than the predicted BMR (P<0.05) in all groups. Obese and overweight DM patients had significantly greater weight, waist circumference, hip circumference, BMI, body surface area, body fat percentage, fat mass, and fat free mass than patients with normal BMI. Except for waist circumference, these body composition measurements were significantly increased in obese DM patients when compared with those in overweight DM patients (P<0.05). Fat-free mass was closely correlated with BMR in both DM patients (r=0.874, P<0.01) and in healthy controls (r=0.902, P<0.01). It was concluded that overweight and obese Chinese adults with type 2 DM had increased BMRs compared with normal-weight controls, which may result from the difference in fat-free mass. PMID- 26838742 TI - Berberine relieves insulin resistance via the cholinergic anti-inflammatory pathway in HepG2 cells. AB - Berberine (BBR) is an isoquinoline alkaloid extracted from Rhizoma coptidis and has been used for treating type 2 diabetes mellitus (T2DM) in China. The development of T2DM is often associated with insulin resistance and impaired glucose uptake in peripheral tissues. In this study, we examined whether BBR attenuated glucose uptake dysfunction through the cholinergic anti-inflammatory pathway in HepG2 cells. Cellular glucose uptake, quantified by the 2-[N-(7 Nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-2-deoxy-D-glucose (2-NBDG), was inhibited by 21% after HepG2 cells were incubated with insulin (10(-6) mol/L) for 36 h. Meanwhile, the expression of alpha7 nicotinic acetylcholine receptor (alpha7nAChR) protein was reduced without the change of acetylcholinesterase (AChE) activity. The level of interleukin-6 (IL-6) in the culture supernatant, the ratio of phosphorylated I-kappa-B kinase-beta (IKkappabeta) Ser181/IKKbeta and the expression of nuclear factor-kappa B (NF-kappaB) p65 protein were also increased. However, the treatment with BBR enhanced the glucose uptake, increased the expression of alpha7nAChR protein and inhibited AChE activity. These changes were also accompanied with the decrease of the ratio of pIKKbeta Ser181/IKKbeta, NF-kappaB p65 expression and IL-6 level. Taken together, these results suggest that BBR could enhance glucose uptake, and relieve insulin resistance and inflammation in HepG2 cells. The mechanism may be related to the cholinergic anti inflammatory pathway and the inhibition of AChE activity. PMID- 26838743 TI - Distinct expression of chemokine-like factor 1 in synovium of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. AB - Chemokine-like factor 1 (CKLF1) is a newly cloned chemotactic cytokine with CCR4 being its functional receptor. Recent evidence demonstrates a role of CKLF1 in arthritis. The aim of this study was to quantify the expression of CKLF1 as well as assess the correlation between CKLF1 and plasma acute-phase markers. Synovium was obtained from 16 osteoarthritis (OA), 15 rheumatoid arthritis (RA) and 10 ankylosing spondylitis (AS) patients undergoing total joint arthroplasty, with other 11 patients treated for meniscal tears during sport accidents serving as normal controls. Levels of CKLF1 and CCR4 mRNA were detected by qRT-PCR, and the expression of CKLF1 was investigated by immunohistochemistry staining, subsequently analyzed with semiquantitative scores. Plasma acute-phase markers of inflammation were determined by ELISA. CKLF1 was found with a particularly up regulated expression in synovim from AS and RA patients, and CCR4 mRNA levels increased in RA patients, not in OA or AS patients. Elevated levels of plasma markers of inflammation including CRP, ESR and D-dimer were observed in RA. Further, significantly positive correlations between relative expression levels of CKLF1 and CRP/ESR in RA patients and a positive correlation between CKLF1 and ESR in AS patients were found. There was no detectable correlation between CKLF1 and plasma D-dimer. This study confirms an increased but different level of CKLF1 in RA, OA and AS patients, all significantly higher than that in controls. Additionally, the significant positive correlations between CKLF1 levels and CRP/ESR in RA and between CKLF1 and ESR suggest that CKLF1 might contribute to the inflammation state and clinical symptoms in these rheumatic diseases. Further studies are required to investigate the utility of targeting specific CKLF1 for symptom control or disease modification in RA and AS. PMID- 26838744 TI - Effects of BRAF(V600E) mutation on Na(+)/I(-) symporter expression in papillary thyroid carcinoma. AB - Radioiodine ablation (RIA) therapy is one of the most important treatments for papillary thyroid carcinoma (PTC), but some patients who received (131)I have radioiodine-refractory disease caused by the decreased expression of the Na(+)/I( ) symporter (NIS). BRAF(V600E) mutation is one possible risk factor that can disturb the NIS expression, but the roles are unclear in clinical practice. This research discussed the association of BRAF(V600E) mutation and NIS expression in PTC tissue and the clinical implications in RIA therapy. 134 PTC samples were collected between June 2013 and June 2014 from Tongji Hospital affiliated to Tongji Medical College, and their clinical characteristics were analyzed. RT-PCR was used to detect the BRAF(V600E) mutation from formalin-fixed paraffin-embedded samples, and immunohistochemistry was applied to detect the NIS expression. IPP software was used to calculate the relative expression quantity of NIS. We found that there was no significant correlation between the absorbance (A) values of NIS and clinicopathologic features in these cases, even thyroid stimulating hormone. BRAF(V600E) mutation showed inhibitory effect on the NIS expression without statistically significant difference in all PTC cases (beta=-0.0195, P=0.085), but in the subgroup without hashimoto's thyroiditis (HT), BRAF(V600E) mutation could significantly inhibit the NIS expression (beta=-0.0257, P=0.046). The results indicate that BRAF(V600E) mutation is correlated with a lower expression of NIS in PTCs without HT, suggesting the radioiodine-refractory effects during RIA therapy in these patients. PMID- 26838745 TI - Neamine inhibits growth of pancreatic cancer cells in vitro and in vivo. AB - Neamine, a non-toxic derivative of neomycin, has recently been shown to have antitumor activities in various types of cancers. However, its effect on pancreatic cancer is still unknown. The study aimed to investigate its antitumor activity on pancreatic cancer and the underlying mechanisms. MTT assay was used to observe the effect of neamine on angiogenin (ANG)-induced AsPC-1 cell proliferation. Tissue microassay and immunofluorescence staining were used to detect the expression of ANG and its nuclear translocation, respectively. Tumor xenografts were established by subcutaneous inoculation of AsPC-1 pancreatic cancer cells into the right flanks of nude mice, and neamine was injected subcutaneously. Immunohistochemistry was done to observe the expression of ANG, CD31 and Ki-67 in tumor xenografts. It was found that neamine blocked the nuclear translocation of ANG effectively and inhibited ANG-induced AsPC-1 cell proliferation in a dose-dependent manner. Neamine had anti-tumor effects on AsPC 1 xenograft models. Consistently, neamine reduced the expression levels of ANG, Ki-67 and CD31 in tumor xenografts. It was concluded that neamine may be a promising agent for treatment of pancreatic cancer. PMID- 26838746 TI - JNK in spinal cord facilitates bone cancer pain in rats through modulation of CXCL1. AB - In patients with advanced cancer, cancer-induced bone pain (CIBP) is a severe and common problem that is difficult to manage and explain. As c-Jun N-terminal kinase (JNK) and chemokine (C-X-C motif) ligand 1 (CXCL1) have been shown to participate in several chronic pain processes, we investigated the role of JNK and CXCL1 in CIBP and the relationship between them. A rat bone cancer pain model was established by intramedullary injection of Walker 256 rat gland mammary carcinoma cells into the left tibia of Sprague-Dawley rats. As a result, intramedullary injection of Walker 256 carcinoma cells induced significant bone destruction and persistent pain. Both phosphorylated JNK1 (pJNK1) and pJNK2 showed time-dependent increases in the ipsilateral spinal cord from day 7 to day 18 after tumor injection. Inhibition of JNK activation by intrathecal administration of SP600125, a selective pJNK inhibitor, attenuated mechanical allodynia and heat hyperalgesia caused by tumor inoculation. Tumor cell inoculation also induced robust CXCL1 upregulation in the ipsilateral spinal cord on day 18 after tumor injection. Inhibition of CXCL1 by intrathecal administration of CXCL1 neutralizing antibody showed a stable analgesic effect. Intrathecal administration of SP600125 reduced CXCL1 increase in the spinal cord, whereas inhibition of CXCL1 in the spinal cord showed no influence on JNK activation. Taken together, these results suggested that JNK activation in spinal cord contributed to the maintenance of CIBP, which may act through modulation of CXCL1. Inhibition of the pJNK/CXCL1 pathway may provide a new choice for treatment of CIBP. PMID- 26838747 TI - Efficacy of different types of self-expandable stents in carotid artery stenting for carotid bifurcation stenosis. AB - Both open and closed loop self-expandable stents were used in carotid artery stenting (CAS) for carotid bifurcation stenosis. We sought to compare the efficacy of two types of stents in CAS. The data of 212 patients treated with CAS (42 and 170 cases implanted with closed and open loop stents, respectively) for carotid bifurcation stenosis and distal filtration protection devices were retrospectively analyzed. Between closed and open loop stents, there were no significant differences in hospitalization duration, NIHSS score before and after the treatment, stenosis at 12th month, and cumulative incidence of primary endpoint events within 30 days or from the 31st day to the 12th month; while there were significant differences in hemodynamic changes and rate of difficulty in recycling distal filtration protection devices. Use of open vs. closed loop stents for carotid bifurcation stenosis seems to be associated with similar incidence of complications, except for greater rate of hemodynamic changes and lower rate of difficulty in recycling the distal filtration protection devices. PMID- 26838748 TI - Minimally invasive percutaneous catheter drainage versus open laparotomy with temporary closure for treatment of abdominal compartment syndrome in patients with early-stage severe acute pancreatitis. AB - This study aimed to examine the clinical efficacy of minimally invasive percutaneous catheter drainage (PCD) versus open laparotomy with temporary closure in the treatment of abdominal compartment syndrome (ACS) in patients with early-stage severe acute pancreatitis (SAP). Clinical data of 212 patients who underwent PCD and 61 patients who were given open laparotomy with temporary closure in our hospital over the last 10-year period were retrospectively analyzed, and outcomes were compared, including total and post-decompression intensive care unit (ICU) and hospital stays, physiological data, organ dysfunction, complications, and mortality. The results showed that the organ dysfunction scores were similar between the PCD and open laparotomy groups 72 h after decompression. In the PCD group, 134 of 212 (63.2%) patients required postoperative ICU support versus 60 of 61 (98.4%) in the open laparotomy group (P<0.001). Additionally, 87 (41.0%) PCD patients experienced complications as compared to 49 of 61 (80.3%) in the open laparotomy group (P<0.001). There were 40 (18.9%) and 32 (52.5%) deaths, respectively, in the PCD and open laparotomy groups (P<0.001). In conclusion, minimally invasive PCD is superior to open laparotomy with temporary closure, with fewer complications and deaths occurring in PCD group. PMID- 26838750 TI - A systematic review of animal and clinical studies on the use of scaffolds for urethral repair. AB - Replacing urethral tissue with functional scaffolds has been one of the challenging problems in the field of urethra reconstruction or repair over the last several decades. Various scaffold materials have been used in animal studies, but clinical studies on use of scaffolds for urethral repair are scarce. The aim of this study was to review recent animal and clinical studies on the use of different scaffolds for urethral repair, and to evaluate these scaffolds based on the evidence from these studies. PubMed and OVID databases were searched to identify relevant studies, in conjunction with further manual search. Studies that met the inclusion criteria were systematically evaluated. Of 555 identified studies, 38 were included for analysis. It was found that in both animal and clinical studies, scaffolds seeded with cells were used for repair of large segmental defects of the urethra, such as in tubular urethroplasty. When the defect area was small, cell-free scaffolds were more likely to be applied. A lot of pre-clinical and limited clinical evidence showed that natural or artificial materials could be used as scaffolds for urethral repair. Urinary tissue engineering is still in the immature stage, and the safety, efficacy, cost effectiveness of the scaffolds are needed for further study. PMID- 26838749 TI - Microwave ablation versus laser ablation in occluding lateral veins in goats. AB - Increasing number of endovenous techniques are available for the treatment of saphenous vein reflux and endovenous laser ablation (EVLA) is a frequently used method. A newly developed alternative, based on thermal therapy, is endovenous microwave ablation (EMA). This study evaluated the effect of the two procedures, in terms of coagulation and histological changes, in occluding lateral veins in goats. Twelve animals were randomized into two group, with 6 treated with EMA (EMA group), and the rest 6 with EVLA (EVLA group). Results of coagulation, including coagulation, fibrinolysis and platelet activation, were assessed at three or four different time points: before, immediately after, 24 h (and 48 h) after ablation. The diameter change, a measure of efficacy, was ultrasonographically measured before and 1 month after the ablation. Histological changes were grossly and microscopically evaluated immediately, 1 and 3 month(s) after the ablation. The length of the ablated vein and preoperative average diameter were comparable between the two groups. In both EMA and EVLA groups, several coagulation parameters, fibrinolysis and platelet activation parameters only underwent slight changes. Ultrasound imaging displayed that the diameter reduction of the veins treated by EMA was significantly larger than by EVLA, in consistent with the results of macroscopic examination. Microscopic examination revealed necrosis and thickening of the vein wall, and occlusion of the lumen within 3 months after ablation in both EMA and EVLA groups. It is concluded that EMA is a minimally invasive therapy, which appears to be safe and effective for treatment of lateral veins in goats. PMID- 26838751 TI - Ultrasound-guided open nephron sparing surgery without renal artery occlusion for central renal tumors. AB - From January 2008 to January 2013, 11 patients with central renal tumors underwent ultrasound-guided open nephron sparing surgery (ONSS) without renal artery occlusion. We removed the lesions, and the cut edges of the tumors were negative. Thus, we deduced that ultrasound-guided ONSS is suitable for the cases with obscure tumor boundary or multiple lesions. It could achieve the purpose of thoroughly removing lesions, as well as to expand the application range of nephron sparing surgery. PMID- 26838752 TI - Low-intensity treadmill exercise promotes rat dorsal wound healing. AB - In order to investigate the promoting effect of low-intensity treadmill exercise on rat dorsal wound healing and the mechanism, 20 Sprague-Dawley rats were randomly divided into two groups: exercise group (Ex) and non-exercise group (non ex). The rats in Ex group were given treadmill exercise for one month, and those in non-ex group raised on the same conditions without treadmill exercise. Both groups received dorsal wound operation with free access to food and water. By two week continuous observation and recording of the wound area, the healing rate was analyzed. The blood sample was collected at day 14 post-operation via cardiac puncture for determination of the number of endothelial progenitor cells (EPCs) by flow cytometry, and the concentrations of relevant cytokines such as basic fibroblast growth factor (bFGF), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were measured by ELISA. The skin tissue around the wound was dissected to observe the vascular density under the microscope after HE staining, to detect the mRNA level of VEGFR2 and angiopoietin 1 (Ang-1) receptor using RT-qPCR, and protein expression of a-smooth muscle actin (alphaSMA) and type III collagen (ColIII) using Western blotting. It was found that the wound area in Ex group was smaller at the same time point than in non-ex group. The number of circulating EPCs was greater and the concentrations of vasoactive factors such as VEGF, eNOS and bFGF were higher in Ex group than in non-ex group. HE staining displayed a higher vessel density in Ex group than in non-ex group. Moreover, the mRNA expression of VEGFR2 and Ang-1 detected in the wound tissue in Ex group was higher than in non-ex group. Meanwhile, the protein expression of alphaSMA and ColIII was more abundant in Ex group than in non-ex group. Conclusively, the above results demonstrate Ex rats had a higher wound healing rate, suggesting low-intensity treadmill exercise accelerates wound healing. The present work may provide some hint for future study of treating refractory wound. PMID- 26838753 TI - Pituitary suppression before frozen embryo transfer is beneficial for patients suffering from idiopathic repeated implantation failure. AB - Long-term gonadotropin-releasing hormone agonist (GnRHa) administration before in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) in infertile women with endometriosis or adenomyosis significantly enhanced the chances of pregnancy in both fresh and frozen embryo transfer cycles. We hypothesized that long-term GnRHa treatment might also be beneficial for the idiopathic repeated implantation failure (RIF) patients. In the 21 patients receiving GnRHa and hormone replacement therapy (G-HRT) protocols for frozen embryo transfer, their data were compared with those of the 56 of frozen/fresh cycles they had previously undergone (previous protocols). Comparison showed that the finial results were significantly better with G-HRT protocols than with their previous protocols, with pregnancy rate, clinical pregnancy rate, implantation rate and on going pregnancy rate being 70%, 60%, 40% and 38% respectively with G-HRT protocols, against 17%, 11%, 6.3% and 5% with previous protocols. The results showed that hormonally controlled endometrial preparation with prior GnRHa suppression could be used for patients who had experienced repeated failures of IVF treatment despite having morphologically optimal embryos, and the treatment may help increase the receptivity of the endometrium in these patients. PMID- 26838755 TI - Cytotoxicity of modified nonequilibrium plasma with chlorhexidine digluconate on primary cultured human gingival fibroblasts. AB - The aim of this study was to investigate the cytotoxicity of modified nonequilibrium plasma with chlorhexidine digluconate (CHX) on human gingival fibroblasts (HGFs), and to evaluate the biosecurity of modified nonequilibrium plasma with 2% CHX as a new method of root canal treatment. Tissue samples taken from human gingiva were primarily cultured and passaged. Cells from passages 3-7 were used. HGFs were treated by modified nonequilibrium plasma with 2% CHX for 0 min (control group), 30 s, 1 min, 1.5 min, 3 min, 5 min, and 10 min, respectively, and then they were incubated for 0, 24, and 48 h. After that, cell counting kit-8 (CCK-8) assay was applied to analyze the cytotoxicity of modified nonequilibrium plasma with 2% CHX on HGFs. There was no significant difference between the 0 h group treated with the modified nonequilibrium plasma for 1 min and the control group (P>0.05). However, there were significant differences between all the other treated groups and the control group (P<0.05). When treated for 1.5 min or shorter, the cell viability was obviously increased; while treated for 3 min or longer, it was obviously reduced. Moreover, when successively cultured for 0, 24, and 48 h, cell viability was decreased at first and then increased in the 3-min-treated and 5-min-treated groups. The modified nonequilibrium plasma with 2% CHX was of no influence on cell viability in 1.5 min treatment, and it could be safely used on root canal treatment. PMID- 26838754 TI - Association of down-regulation of CD109 expression with up-expression of Smad7 in pathogenesis of psoriasis. AB - Transforming growth factor (TGF)-beta signaling plays an important role in the pathogenesis of psoriasis. CD109, a novel TGF-beta co-receptor, which inhibits TGF-beta signaling by enhancing Smad7-dependent degradation of TGF-beta type I receptor (TGF-beta RI), is abnormally expressed in psoriasis. To date, the expression of Smad7 and the correlation between CD109 and Smad7 expression in psoriasis have not been fully elucidated. This study was designed to investigate the expression and the correlation of CD109 and TGF-beta signaling associated proteins in psoriasis and their roles in the pathogenesis of psoriasis. Thirty two psoriasis specimens were subjected to immunohistochemical staining for CD109, Smad7, TGF-beta RI and Ki67. Ten normal skin (NS) specimens served as controls. The positive expression rate (% positive cells) of Smad7 and Ki67 in psoriasis was significantly higher than in NS (62.6%+/-19.9% vs. 17.2%+/-4.4%, and 50.7%+/ 14.3% vs. 19.5%+/-3.2%, respectively, P<0.001), and the expression levels of CD109 and TGF-beta RI were reduced significantly in psoriasis as compared with NS (8.1%+/-6.7% vs. 35.8%+/-6.7% and 27.3%+/-3.4% vs. 3.0%+/-3.4%, respectively, P<0.001). There were significantly negative correlations between CD109 and Smad7 (r=-0.831, P<0.01). These findings indicated that CD109 might play a certain role in the pathogenesis of psoriasis. Lower expression of CD109 and TGF-beta RI was highly correlated with higher expression of Smad7 and Ki67, suggesting that CD109 may induce the pathogenesis of psoriasis through Smad7-mediated degradation of TGF-beta RI, and lead to the termination of TGF-beta signaling. PMID- 26838756 TI - A systematic review on efficacy and safety of gasless laparoscopy in the management of uterine leiomyoma. AB - Uterine leiomyoma causes considerable morbidity in women. This study systematically reviewed the efficacy and safety of gasless laparoscopic myomectomy (GLM) in the management of uterine leiomyoma by comparing GLM with other minimally invasive procedures. Cochrane Library, Pub- Med, EMBASE, Web of Science, WANFANG database and China National Knowledge Infrastructure (CNKI) were searched for studies published in English or Chinese between January 1995 and May 2015, and related references were traced. Study outcomes from randomized controlled trials and retrospective cohort studies were presented as mean difference (MD) or odds ratio (OR) with a 95% confidence interval (CI). Seventeen studies (including 1862 patients) meeting the inclusion criteria, including 934 treated with GLM and 928 treated with other minimally invasive procedures were reviewed. The results of meta-analysis revealed that GLM resulted in significantly shorter operating time [MD=-10.34, 95% CI (-18.12,-2.56), P<0.00001], shorter hospital stay [MD=-0.47, 95% CI (-0.88,-0.06)], less time to flatus [MD=-2.04, 95% CI (-2.59,-1.48)], less postoperative complications [OR=0.20, 95% CI (0.06, 0.62)] and less blood loss [MD =-30.74, 95% CI (-47.50, 13.98)]. On the other hand, there were no significant differences in duration of post-operative fever [MD=-0.52, 95% CI (-1.46, 0.42)] between the two groups. Additionally, GLM was associated with lower febrile morbidity, lower postoperative abdominal pain, and higher postoperative hemoglobin than other minimally invasive procedures for the treatment of uterine leiomyoma. In conclusion, GLM and other minimally invasive procedures are feasible, safe, and reliable for uterine leiomyoma treatment. However, available studies show that GLM is more effective and safer than other minimally invasive approaches. PMID- 26838757 TI - Impact of village-based health education of tobacco control on the current smoking rate in Chinese rural areas. AB - The number of smokers in Chinese rural areas is more than 200 million, which is twice that in cities. It is very significant to carry out tobacco control interventions in rural areas. We performed this community intervention study to evaluate the efficacy of village-based health education of tobacco control on the male current smoking rate in rural areas. The population of this study was the males above 15 years old from 6 villages in rural areas. The villages were randomly assigned to intervention group or control group (3 villages in each group). Self-designed smoking questionnaire was applied. The intervention group received the village-based health education of tobacco control for one year. The primary outcome measurement was the male current smoking rate. In the baseline investigation, completed surveys were returned by 814 male residents from the control group and 831 male residents from the intervention group. The male current smoking rate in the control group and the intervention group was 61.2% and 58.5%, respectively, before intervention. There was no significant difference between these two groups (P>0.05). After one-year intervention, the current smoking rate in the intervention group (51.2%) was significantly lower than that in the control group (62.8%) (P<0.001). Our study suggested that the village based health education of tobacco control was effective in lowering the male current smoking rate in rural areas, which could be a suitable and feasible way for tobacco control in the Chinese rural areas. PMID- 26838758 TI - Evaluation of role of Notch3 signaling pathway in human lung cancer cells. AB - There is still a debate on the extent to which Notch3 signaling is involved in lung carcinogenesis and whether such function is dependent on cancer type or not. PURPOSE: To evaluate Notch3 expression in different types of human lung cancer cells. METHODS: Notch3 was detected in human lung cancer cell lines and in tissues. Then, small interfering RNA (siRNA) was used to down-regulate the expression of Notch3 in H69AR small cell lung carcinoma (SCLC) cells; two non small cell lung carcinoma (NSCLC) cells; A549 adenocarcinoma (ADC); and H2170 squamous cell carcinoma (SCC). In addition, Notch3 intracellular domain (N3ICD) plasmid was transfected into H1688 human SCLC cells. We observed the effect of deregulating Notch3 signaling on the following cell properties: Notch-related proteins, cell morphology, adhesion, epithelial-mesenchymal transition (EMT), motility, proliferation and neuroendocrine (NE) features of SCLC. RESULTS: Notch3 is mainly expressed in NSCLC, and the expression of Notch1, Hes1 and Jagged1 is affected by Notch3. Notch3 has opposite functions in SCLC and NSCLC, being a tumor suppressor in the former and tumor promoting in the latter, in the context of cell adhesion, EMT and motility. Regarding cell proliferation, we found that inhibiting Notch3 in NSCLC decreases cell proliferation and induces apoptosis in NSCLC. Notch3 has no effect on cell proliferation or NE features of SCLC. CONCLUSION: Notch3 signaling in lung carcinoma is dependent on cell type. In SCLC, Notch3 behaves as a tumor suppressor pathway, while in NSCLC it acts as a tumor-promoting pathway. PMID- 26838760 TI - Corrigendum: Transcriptome analysis identifies genes involved in adventitious branches formation of Gracilaria lichenoides in vitro. PMID- 26838759 TI - Passive smoking and cooking oil fumes (COF) may modify the association between tea consumption and oral cancer in Chinese women. AB - PURPOSE: To evaluate the confounding effects of passive smoking and COF exposure on association between tea and oral cancer in Chinese women. METHODS: A case control study including 207 female oral cancer cases and 480 age-matched controls was performed in Fujian, China. Data were collected with a structured questionnaire by face-to-face interviews. The effects of tea consumption on oral cancer were, respectively, adjusted for Model-1 and Model-2 using logistic regression analysis. Model-1 did not adjusted for passive smoking and COF; Model 2 included the variables in Model-1, passive smoking and COF. RESULTS: Tea consumption was associated with a decreased risk of oral cancer in females: The OR was 0.498 (95 % CI 0.312-0.795) for Model-1 and 0.565 (95 % CI 0.352-0.907) for Model-2. The ORs for all the categories of tea consumption estimated by Model 2 were slightly higher than Model-1. When stratified by passive smoking, the statistically significant association between tea drinking and oral cancer was only emerged in non-passive smoking women. Stratification by COF found tea drinking was still associated with a decreased risk of oral cancer for women who have light-COF exposure, but an increased risk for those who subjected to heavy exposure. A negative, multiplicative interaction was found between tea consumption and COF exposure for oral cancer, but not found between tea consumption and passive smoking. CONCLUSIONS: Tea consumption reduces the risk of oral cancer in Chinese women, but this effect is modified by the carcinogenic effects of passive smoking and COF exposure. PMID- 26838761 TI - An Integrated Approach for Screening and Identification of Positive Allosteric Modulators of N-Methyl-D-Aspartate Receptors. AB - N-methyl-D-aspartate receptors (NMDARs) are ionotropic glutamate receptors that play an important role in synaptic plasticity and learning and memory formation. Malfunctioning of NMDARs, in particular the reduction in NMDAR activity, is thought to be implicated in major neurological disorders. NMDAR positive allosteric modulators (PAMs) represent potential therapeutic interventions for restoring normal NMDAR function. We report a novel screening approach for identification and characterization of NMDAR-PAMs. The approach combines high throughput fluorescence imaging with automated electrophysiological recording of glutamate-evoked responses in HEK-293 cells expressing NR1/NR2A NMDAR subunits. Initial high-throughput screening (HTS) of a chemical library containing >810,000 compounds using a calcium flux assay in 1536-well plate format identified a total of 864 NMDAR-PAMs. Concentration response determination in both calcium flux and automated electrophysiological assays found several novel chemical series with EC50 values between 0.49 and 10 uM. A small subset (six series) was selected and analyzed for pharmacological properties, subtype selectivity, mode of action, and activity at native NMDARs. Our approach demonstrates the successful application of HTS functional assays that led to identification of NMDAR-PAMs providing the foundation for further medicinal chemistry work that may lead to novel therapies for treatment of cognitive impairment associated with Alzheimer's disease and schizophrenia. PMID- 26838763 TI - Allenes, versatile unsaturated motifs in transition-metal-catalysed [2+2+2] cycloaddition reactions. AB - The development of efficient reactions that enable the construction of multiple bonds and/or stereogenic centres in a single synthetic operation is of great interest for greener and step-economical syntheses of complex organic targets. Transition-metal-catalysed [2+2+2] cycloadditions excell in this regard: no fewer than three new sigma bonds and a new ring system are formed from simple unsaturated components. Allenes constitute an important subclass among these. They are more reactive than simple alkenes and generate sp(3) centres, with important stereochemical implications. In addition, further manipulation of the resulting cycloadduct through the remaining double bond is possible, increasing molecular complexity. This tutorial review highlights the value that allenes have as reagents in [2+2+2] cycloaddition and their great versatility for the development of methods to generate complex architectures. PMID- 26838762 TI - Phenoloxidase activity in the infraorder Isoptera: unraveling life-history correlates of immune investment. AB - Within the area of ecological immunology, the quantification of phenoloxidase (PO) activity has been used as a proxy for estimating immune investment. Because termites have unique life-history traits and significant inter-specific differences exist regarding their nesting and foraging habits, comparative studies on PO activity can shed light on the general principles influencing immune investment against the backdrop of sociality, reproductive potential, and gender. We quantified PO activity across four termite species ranging from the phylogenetically basal to the most derived, each with their particular nesting/foraging strategies. Our data indicate that PO activity varies across species, with soil-dwelling termites exhibiting significantly higher PO levels than the above-ground wood nester species which in turn have higher PO levels than arboreal species. Moreover, our comparative approach suggests that pathogenic risks can override reproductive potential as a more important driver of immune investment. No gender-based differences in PO activities were recorded. Although termite PO activity levels vary in accordance with a priori predictions made from life-history theory, our data indicate that nesting and foraging strategies (and their resulting pathogenic pressures) can supersede reproductive potential and other life-history traits in influencing investment in PO. Termites, within the eusocial insects, provide a unique perspective for inferring how different ecological pressures may have influenced immune function in general and their levels of PO activity, in particular. PMID- 26838764 TI - Suppression of LPS-induced tau hyperphosphorylation by serum amyloid A. AB - BACKGROUND: Accumulation of hyperphosphorylated tau is a major neuropathological feature of tauopathies including Alzheimer's disease (AD). Serum amyloid A (SAA), an acute-phase protein with cytokine-like property, has been implicated in amyloid deposition. It remains unclear whether SAA affects tau hyperphosphorylation. METHODS: Potential involvement of SAA in tau hyperphosphorylation was examined using intracerebral injection of SAA, and in Saa3 (-/-) mice receiving systemic administration of lipopolysaccharide (LPS). Induced SAA expression and microglial activation were evaluated in these mice using real-time PCR and/or immunofluorescence staining. Cultured primary neuronal cells were treated with condition media (CM) from SAA-stimulated primary microglial cells. The alteration in tau hyperphosphorylation was determined using Western blotting. RESULTS: Saa3 is the predominant form of SAA proteins induced by LPS in the mouse brain that co-localizes with neurons. Overexpression of SAA by intracerebral injection attenuated tau hyperphosphorylation in the brain. Conversely, Saa3 deficiency enhanced tau phosphorylation induced by systemic LPS administration. Intracerebral injection of SAA also induced the activation of microglia in the brains. IL-10 released to CM from SAA-stimulated microglia attenuated tau hyperphosphorylation in cultured primary neurons. IL-10 neutralizing antibody reversed the effect of SAA in the attenuation of tau phosphorylation. CONCLUSIONS: LPS-induced expression of SAA proteins in the brain leads to the activation of microglia and release of IL-10, which in turn suppresses tau hyperphosphorylation in a mouse model of systemic inflammation. PMID- 26838766 TI - Current advances in targeted therapies for metastatic gastric cancer: improving patient care. AB - In this article, we review the literature on the current advances in targeted therapies for metastatic gastric cancer aimed at improving patient care. We conclude that the key to guiding targeted therapy is individual biomarkers, which are not completely elucidated. HER2 overexpression is the only predictive biomarker currently in use. Furthermore, it is necessary to understand that gastric tumors are heterogeneous; therefore, is impossible to evaluate a novel biological compound without evaluating personal biomarkers. The selection of patients who are able to receive each treatment is paramount for improving advanced gastric cancer survival and reducing unnecessary costs. PMID- 26838767 TI - Suppurative Granulomatous Cholecystitis in a Pediatric Chronic Carrier with Salmonella enterica serotype Typhi: A Case Report and Review of Literature. AB - Bacterial infection of Salmonella enterica serotype Typhi is rare in the United States but endemic in many developing countries. Approximately 3-5% of patients become chronic asymptomatic carriers. We describe an atypical presentation of S. enterica serotype Typhi infection in a 10-year-old male, whose cholecystechtomy and bile culture revealed chronic carrier status despite negative stool tests and the absence of gallstones. The gallbladder showed marked thickening of the wall with an intense suppurative granulomatous reaction. PMID- 26838765 TI - Drinking in the last chance saloon: luck egalitarianism, alcohol consumption, and the organ transplant waiting list. AB - The scarcity of livers available for transplants forces tough choices upon us. Lives for those not receiving a transplant are likely to be short. One large group of potential recipients needs a new liver because of alcohol consumption, while others suffer for reasons unrelated to their own behaviour. Should the former group receive lower priority when scarce livers are allocated? This discussion connects with one of the most pertinent issues in contemporary political philosophy; the role of personal responsibility in distributive justice. One prominent theory of distributive justice, luck egalitarianism, assesses distributions as just if, and only if, people's relative positions reflect their exercises of responsibility. There is a principled luck egalitarian case for giving lower priority to those who are responsible for their need. Compared to the existing literature favouring such differentiation, luck egalitarianism provides a clearer rationale of fairness, acknowledges the need for individual assessments of responsibility, and requires initiatives both inside and outside of the allocation systems aimed at mitigating the influence from social circumstances. Furthermore, the concrete policies that luck egalitarians can recommend are neither too harsh on those who make imprudent choices nor excessively intrusive towards those whose exercises of responsibility are assessed. PMID- 26838768 TI - Actions on social determinants and interventions in primary health to improve mother and child health and health equity in Morocco. AB - BACKGROUND: Over the last two decades, Moroccan authorities launched a number of actions and strategies to enhance access to health services and improve health outcomes for the whole population in general and for mother and child in particular. The Ministry of Health launched the action plans 2008-2012 and 2012 2016 and created the maternal mortality surveillance system. The Moroccan government opted for national health coverage through a mandatory health insurance and a scheme of health assistance to the poorest households. Other initiatives were devoted indirectly to health by acting on social determinants of health and poverty reduction. In this paper, we present results of an evaluation of interventions and programmes and their impact on health inequity in Morocco. METHOD: We used data provided by national surveys over the last decades, information released on the website of the Ministry of Health, documentation published by the Moroccan government and international reports and studies related to Morocco and published by international bodies like the World Health Organisation, United Nations Development Programme, United Nations Population Fund, UNICEF, UNESCO and the World Bank. A short review of scientific publications was also carried out in order to select papers published on health equity, social determinants, health system and interventions in primary health in Morocco. Inferential and descriptive statistics (including principal component analysis) were carried out using software SPSS version 18. RESULTS: The findings indicate that substantial achievements were obtained in terms of access to health care and health outcomes for the whole Moroccan population in general and for mothers and children in particular. However, achievements are unfairly distributed between advantaged and less advantaged regions, literate and illiterate women, rural and urban areas, and rich and poor segments of the Moroccan population. DISCUSSION: Studies have shown that it is difficult to trace the effect of a primary health intervention on the access to health care due to synergetic and overlapping effect of interventions and initiatives aiming to improve the wellbeing of the Moroccan population. Descriptive and inferential statistics were used to illustrate the correlation existing between different variables measuring access to health and health outcomes on one side and variables like income, education, employment and health staff on the other side. CONCLUSION: In Morocco, average access to health care and services as well as health outcomes have improved during the last decades. However, socio-economic inequalities and health inequity are persistent. The present study indicates that urgent and efficient actions on social determinants of health are needed in order to sustain average achievements and improve health equity for the whole Moroccan population. PMID- 26838769 TI - Caloric Restriction in Older Adults-Differential Effects of Weight Loss and Reduced Weight on Brain Structure and Function. AB - Dietary modifications such as caloric restriction (CR) have been suggested as a means to improve memory and prevent age-related decline. However, it is unclear whether those effects remain stable over time or are related specifically to negative energy balance during the weight loss phase of CR. Using a randomized interventional design, we investigated changes in recognition memory and neural correlates in postmenopausal obese women (n = 19): 1) after intense weight loss in the course of a 12-week low-caloric diet (reduced body weight and negative energy balance) and 2) after having sustained the reduced weight over 4 more weeks (reduced body weight, but energy balance equilibrium). Participants were contrasted to a control group (n = 18) instructed not to change dietary habits. In the CR group, we found improved recognition memory, paralleled by increased gray matter volume in inferior frontal gyrus and hippocampus, and augmented hippocampal resting-state functional connectivity to parietal areas. Moreover, effects were specific for transient negative energy balance and could not be detected after subsequent weight maintenance. Our data demonstrate for the first time in humans that beneficial effects of CR on brain structure and function are due to weight loss rather than an overall reduced weight. PMID- 26838770 TI - Variable Temporal Integration of Stimulus Patterns in the Mouse Barrel Cortex. AB - Making sense of the world requires distinguishing temporal patterns and sequences lasting hundreds of milliseconds or more. How cortical circuits integrate over time to represent specific sensory sequences remains elusive. Here we assessed whether neurons in the barrel cortex (BC) integrate information about temporal patterns of whisker movements. We performed cell-attached recordings in anesthetized mice while delivering whisker deflections at variable intervals and compared the information carried by neurons about the latest interstimulus interval (reflecting sensitivity to instantaneous frequency) and earlier intervals (reflecting integration over timescales up to several hundred milliseconds). Neurons carried more information about the latest interval than earlier ones. The amount of temporal integration varied with neuronal responsiveness and with the cortical depth of the recording site, that is, with laminar location. A subset of neurons in the upper layers displayed the strongest integration. Highly responsive neurons in the deeper layers encoded the latest interval but integrated particularly weakly. Under these conditions, BC neurons act primarily as encoders of current stimulation parameters; however, our results suggest that temporal integration over hundreds of milliseconds can emerge in some neurons within BC. PMID- 26838772 TI - Radiologic Evaluation of Mesenchymal Tumors of the Female Genital Tract. AB - Mesenchymal neoplasms of the female genital tract are a diverse group of tumors, of which the most common are smooth muscle tumors. There is a significant overlap in the imaging characteristics of benign and malignant tumors and final diagnosis often requires pathologic correlation. However, familiarity with typical radiologic features, common imaging pitfalls, and the utility of different imaging modalities can be valuable in the evaluation of mesenchymal tumors. This article highlights the imaging features of the most commonly encountered mesenchymal tumors in the female genital tract. PMID- 26838773 TI - Mesenchymal Lesions of the Lower Genital Tract. AB - A variety of site-specific mesenchymal lesions of the lower genital tract may occur, which are often diagnostically challenging because of their morphologic overlap. Some of this morphologic homogeneity presumably stems from a potentially shared origin from the specialized superficial stroma of the distal female genital tract. Despite shared appearances, morphologic distinction remains the gold standard for diagnosis of most of these lesions, as immunoperoxidase staining is often not helpful in their distinction. PMID- 26838771 TI - NgR1: A Tunable Sensor Regulating Memory Formation, Synaptic, and Dendritic Plasticity. AB - Nogo receptor 1 (NgR1) is expressed in forebrain neurons and mediates nerve growth inhibition in response to Nogo and other ligands. Neuronal activity downregulates NgR1 and the inability to downregulate NgR1 impairs long-term memory. We investigated behavior in a serial behavioral paradigm in mice that overexpress or lack NgR1, finding impaired locomotor behavior and recognition memory in mice lacking NgR1 and impaired sequential spatial learning in NgR1 overexpressing mice. We also investigated a role for NgR1 in drug-mediated sensitization and found that repeated cocaine exposure caused stronger locomotor responses but limited development of stereotypies in NgR1 overexpressing mice. This suggests that NgR1-regulated synaptic plasticity is needed to develop stereotypies. Ex vivo magnetic resonance imaging and diffusion tensor imaging analyses of NgR1 overexpressing brains did not reveal any major alterations. NgR1 overexpression resulted in significantly reduced density of mature spines and dendritic complexity. NgR1 overexpression also altered cocaine-induced effects on spine plasticity. Our results show that NgR1 is a negative regulator of both structural synaptic plasticity and dendritic complexity in a brain region specific manner, and highlight anterior cingulate cortex as a key area for memory related plasticity. PMID- 26838774 TI - Smooth Muscle Tumors of the Female Genital Tract. AB - Smooth muscle tumors are the most common among mesenchymal tumors in the female genital tract. The vast majority of these neoplasms are clinically benign and easy to diagnose. In contrast, leiomyosarcomas are highly aggressive tumors that may pose considerable diagnostic problems when they display unusual (myxoid or epithelioid) morphology, ambiguous histologic features for malignancy, or an unusual anatomic distribution. Diagnostic criteria for these problematic tumors vary depending on the site and type of histologic differentiation, and are based on a combination of 3 major criteria: (1) moderate to severe cytologic atypia; (2) increased mitotic index; and (3) tumor cell necrosis. Certain benign smooth muscle proliferations may show worrisome histologic features or unusual growth patterns, causing concern for leiomyosarcoma. Furthermore, other tumors, including perivascular epithelioid tumors, may mimic leiomyosarcoma. Careful attention to the clinical and anatomic setting, cytologic and architectural features, and immunohistochemical characteristics are helpful in distinguishing these entities. This article discusses conventional smooth muscle tumors as well as unusual subtypes, with emphasis on the diagnostic criteria and problems in differential diagnosis that arise at each site within the female genital tract. PMID- 26838775 TI - Endometrial/ioid Stromal Tumors and Related Neoplasms of the Female Genital Tract. AB - Endometrial/ioid stromal tumors comprise a spectrum of mesenchymal neoplasms, ranging from benign to low-grade malignancy to undifferentiated sarcomas, which occur predominantly in the uterus but may rarely originate at extrauterine sites, most commonly in the ovary. These tumors and their morphologic variants are important to recognize as they often cause diagnostic difficulties. This review focuses on the diagnostic criteria and differential diagnosis, including the role of immunohistochemistry. PMID- 26838776 TI - Mixed Mullerian Tumors of the Female Genital Tract. AB - Malignant mixed mullerian tumor (MMMT) and mullerian/mesodermal adenosarcoma are 2 of the most common mixed mullerian tumors of the female genital tract. MMMT is a biphasic neoplasm, composed of morphologically malignant epithelial and stromal components. MMMT should be distinguished from endometrioid adenocarcinoma with spindle cell elements, "dedifferentiated" endometrioid carcinoma, and combined adenocarcinoma and neuroendocrine carcinoma. Adenosarcoma is also biphasic; it is composed of morphologically benign or low-grade appearing epithelial components and malignant stromal components. The differential diagnosis of adenosarcoma includes MMMT, endometrial stromal tumor containing endometrioid glands, benign endometrial or endocervical polyp, adenofibroma, adenomyoma, including atypical polypoid adenomyoma, botryoid embryonal rhabdomyosarcoma (sarcoma botryoides), and endometriosis, including polypoid endometriosis. Gross and microscopic features, including immunophenotype, should permit discrimination of the various entities. PMID- 26838777 TI - Cellular Fibromatous Neoplasms of the Ovary. AB - Many ovarian tumors composed primarily of fibroblastic cells are fibromas of usual type, and generally do not pose diagnostic difficulty. These tumors can be diagnosed accurately in most instances based on morphology without needing immunohistochemistry. Approximately 10% of fibromatous neoplasms, however, exhibit increased cellularity and mitotic activity, and, in the presence of the former or both features, are classified as cellular fibroma or mitotically active cellular fibroma. Distinguishing these entities from fibrosarcoma, an exceptionally uncommon ovarian malignancy, is important. This article reviews fibromatous ovarian tumors, emphasizing cellular fibromas and their differential diagnosis. PMID- 26838778 TI - Miscellaneous Pseudotumors and Mesenchymal Tumors of the Female Genital Tract. AB - Benign and malignant soft tissue tumors and pseudotumors can rarely arise anywhere in the female genital tract. Their pathologic features as well as behavior typically overlap with those described in tumors involving typical locations. However, due to their rarity, not infrequently these tumors represent a diagnostic challenge. Their diagnosis should be based on careful gross examination, thorough sampling, and morphologic evaluation, applying a selected immunohistochemical panel and molecular studies. Accurate classification of these tumors is important because their clinical behavior, prognosis, and therapy differ markedly. This article outlines several mesenchymal lesions reported in the female genital tract, encompassing recent histologic, immunohistochemical, and molecular findings, with special emphasis on problems in the differential diagnosis. PMID- 26838779 TI - Immunohistochemical Markers of Value in the Diagnosis of Mesenchymal Lesions of the Female Genital Tract. AB - Pure mesenchymal tumors may occur anywhere in the female genital tract, but they are most common in the uterine corpus, leiomyoma being by far the most prevalent. These tumors, and other uncommon mesenchymal lesions within the uterine corpus and elsewhere in the female genital tract, may result in several diagnostic problems. Morphology remains paramount and, in most cases, an unequivocal diagnosis can be made based on examination of the hematoxylin and eosin stained sections, combined with an appreciation of the clinical and gross pathologic features. In difficult cases, immunohistochemistry can significantly contribute to the final diagnosis. In this article, the immunohistochemistry of neoplastic and nonneoplastic mesenchymal lesions of the female genital tract is discussed site by site, concentrating on markers that are of value in diagnosis and in differential diagnosis. The immunophenotype of mixed epithelial and mesenchymal neoplasms and pure epithelial neoplasms with a component of spindle cells is discussed, where appropriate, because these can enter into the differential diagnosis of a pure mesenchymal lesion. PMID- 26838780 TI - Cytogenetics of Mesenchymal Tumors of the Female Genital Tract. AB - A great diversity of chromosome alterations have been reported in mesenchymal tumors of the female genital tract, particularly in the uterus. Some of these alterations specifically identify a certain tumor type. Cytogenetic studies on benign proliferations have not only demonstrated clonal chromosome changes, but have also pointed out clustering of aberrations to specific chromosome regions. For example, distinct cytogenetic subgroups have been described in uterine leiomyomas with overlapping histologic features. These findings may ultimately correlate with specific parameters, such as course of the disease, response to therapy, and recurrence. Moreover, such data may give a clue to an understanding of the biologic basis for distinctive behavior of benign versus malignant mesenchymal proliferations. No specific chromosomal abnormalities have been described in malignant mesenchymal tumors, with the exception of low-grade endometrial stromal sarcomas. This article reviews the information currently available on genetic changes in mesenchymal tumors of the female genital tract and, more specifically, those reported in the uterus, where they have been more frequently studied. PMID- 26838781 TI - Molecular Genetics of Mesenchymal Tumors of the Female Genital Tract. AB - Mesenchymal tumors of the female genital tract are a heterogeneous group of neoplasms that can be classified based on cellular differentiation into 3 main groups: smooth muscle tumors, endometrial stromal tumors, and other differentiated and undifferentiated tumors. Genomic analysis techniques have revealed important genetic aberrations such as the t(7;17) translocation, resulting in JAZF1-JJAZ1 gene fusion, characteristic of endometrial stromal tumors. These analyses have demonstrated genetic complexity and heterogeneity in many mesenchymal tumor types. This article focuses on current understanding of the molecular genetics of mesenchymal tumors of the female genital tract, with emphasis on diagnostic and prognostic molecular features. PMID- 26838783 TI - Preface. PMID- 26838782 TI - Mesenchymal Tumors of the Female Genital Tract: Treatment. AB - Mesenchymal tumors of the female genital tract include various benign and malignant neoplasms. Mesenchymal tumors may arise from the stroma or associated elements of the organ of origin, such as connective tissue, vascular or neural structures, or others. Malignant mesenchymal tumors of the female genital tract represent a rare group of gynecologic cancers. They are generally aggressive tumors, with a propensity for local and distant recurrence. The mainstay of treatment usually involves surgical excision of the primary tumor. Malignant mesenchymal tumors of the female genital tract are generally refractory to systemic chemotherapy and radiation therapy. This review highlights the treatment options for the most common types of mesenchymal tumors of the female genital tract. PMID- 26838784 TI - Chemical Endoplasmic Reticulum Chaperone Alleviates Doxorubicin-Induced Cardiac Dysfunction. AB - RATIONALE: Doxorubicin is an effective chemotherapeutic agent for cancer, but its use is often limited by cardiotoxicity. Doxorubicin causes endoplasmic reticulum (ER) dilation in cardiomyocytes, and we have demonstrated that ER stress plays important roles in the pathophysiology of heart failure. OBJECTIVE: We evaluated the role of ER stress in doxorubicin-induced cardiotoxicity and examined whether the chemical ER chaperone could prevent doxorubicin-induced cardiac dysfunction. METHODS AND RESULTS: We confirmed that doxorubicin caused ER dilation in mouse hearts, indicating that doxorubicin may affect ER function. Doxorubicin activated an ER transmembrane stress sensor, activating transcription factor 6, in cultured cardiomyocytes and mouse hearts. However, doxorubicin suppressed the expression of genes downstream of activating transcription factor 6, including X-box binding protein 1. The decreased levels of X-box binding protein 1 resulted in a failure to induce the expression of the ER chaperone glucose-regulated protein 78 which plays a major role in adaptive responses to ER stress. In addition, doxorubicin activated caspase-12, an ER membrane-resident apoptotic molecule, which can lead to cardiomyocyte apoptosis and cardiac dysfunction. Cardiac-specific overexpression of glucose-regulated protein 78 by adeno-associated virus 9 or the administration of the chemical ER chaperone 4-phenylbutyrate attenuated caspase 12 cleavage, and alleviated cardiac apoptosis and dysfunction induced by doxorubicin. CONCLUSIONS: Doxorubicin activated the ER stress-initiated apoptotic response without inducing the ER chaperone glucose-regulated protein 78, further augmenting ER stress in mouse hearts. Cardiac-specific overexpression of glucose regulated protein 78 or the administration of the chemical ER chaperone alleviated the cardiac dysfunction induced by doxorubicin and may facilitate the safe use of doxorubicin for cancer treatment. PMID- 26838785 TI - NSun2 Deficiency Protects Endothelium From Inflammation via mRNA Methylation of ICAM-1. AB - RATIONALE: Vascular endothelial inflammation, including the expression of intercellular adhesion molecule 1 (ICAM-1), is a key event in vascular diseases. However, the mechanisms underlying the regulation of ICAM-1 are largely unknown. OBJECTIVE: To investigate the mechanisms on the regulation of ICAM-1 by NOP2/Sun domain family, member 2 (NSun2)-mediated mRNA methylation and the impact of NSun2 ICAM-1 regulatory process in vascular inflammation and allograft arteriosclerosis. METHODS AND RESULTS: By using in vitro, in cells, and in vivo methylation assays, we showed that the tRNA methyltransferase NSun2 methylated the ICAM-1 mRNA. Methylation by NSun2 promoted the translation of ICAM-1, thereby increasing the adhesion of leukocytes to endothelial cells. Tumor necrosis factor alpha or homocysteine activated the methyltransferase activity of NSun2 by repressing the phosphorylation of NSun2 by Aurora-B. The levels of ICAM-1 induction and of leukocyte adhesion to vascular endothelium observed with homocysteine treatment in wild-type rats were markedly decreased in NSun2(-/-) rats. In a rat model of aortic allograft, the lack of donor NSun2 impaired the formation of allograft arteriosclerosis. CONCLUSIONS: NSun2 upregulates the expression of ICAM-1 by methylating ICAM-1 mRNA. This regulatory process impacts on vascular inflammation and allograft arteriosclerosis. PMID- 26838786 TI - DNA Methylation Indicates Susceptibility to Isoproterenol-Induced Cardiac Pathology and Is Associated With Chromatin States. AB - RATIONALE: Only a small portion of the known heritability of cardiovascular diseases, such as heart failure, can be explained based on single-gene mutations. Chromatin structure and regulation provide a substrate through which genetic differences in noncoding regions may affect cellular function and response to disease, but the mechanisms are unknown. OBJECTIVE: We conducted genome-wide measurements of DNA methylation in different strains of mice that are susceptible and resistant to isoproterenol-induced dysfunction to test the hypothesis that this epigenetic mark may play a causal role in the development of heart failure. METHODS AND RESULTS: BALB/cJ and BUB/BnJ mice, determined to be susceptible and resistant to isoproterenol-induced heart failure, respectively, were administered the drug for 3 weeks via osmotic minipump. Reduced representational bisulfite sequencing was then used to compare the differences between the cardiac DNA methylomes in the basal state between strains and then after isoproterenol treatment. Single-base resolution DNA methylation measurements were obtained and revealed a bimodal distribution of methylation in the heart, enriched in lone intergenic CpGs and depleted from CpG islands around genes. Isoproterenol induced global decreases in methylation in both strains; however, the basal methylation pattern between strains shows striking differences that may be predictive of disease progression before environmental stress. The global correlation between promoter methylation and gene expression (as measured by microarray) was modest and revealed itself only with focused analyses of transcription start site and gene body regions (in contrast to when gene methylation was examined in toto). Modules of comethylated genes displayed correlation with other protein-based epigenetic marks, supporting the hypothesis that chromatin modifications act in a combinatorial manner to specify transcriptional phenotypes in the heart. CONCLUSIONS: This study provides the first single-base resolution map of the mammalian cardiac DNA methylome and the first case-control analysis of the changes in DNA methylation with heart failure. The findings demonstrate marked genetic differences in DNA methylation that are associated with disease progression. PMID- 26838787 TI - LOX Mutations Predispose to Thoracic Aortic Aneurysms and Dissections. AB - RATIONALE: Mutations in several genes have been identified that are responsible for 25% of families with familial thoracic aortic aneurysms and dissections. However, the causative gene remains unknown in 75% of families. OBJECTIVES: To identify the causative mutation in families with autosomal dominant inheritance of thoracic aortic aneurysms and dissections. METHODS AND RESULTS: Exome sequencing was used to identify the mutation responsible for a large family with thoracic aortic aneurysms and dissections. A heterozygous rare variant, c.839G>T (p.Ser280Arg), was identified in LOX, encoding a lysyl oxidase, that segregated with disease in the family. Sanger and exome sequencing was used to investigate mutations in LOX in an additional 410 probands from unrelated families. Additional LOX rare variants that segregated with disease in families were identified, including c.125G>A (p.Trp42*), c.604G>T (p.Gly202*), c.743C>T (p.Thr248Ile), c.800A>C (p.Gln267Pro), and c.1044T>A (p.Ser348Arg). The altered amino acids cause haploinsufficiency for LOX or are located at a highly conserved LOX catalytic domain, which is relatively invariant in the population. Expression of the LOX variants p.Ser280Arg and p.Ser348Arg resulted in significantly lower lysyl oxidase activity when compared with the wild-type protein. Individuals with LOX variants had fusiform enlargement of the root and ascending thoracic aorta, leading to ascending aortic dissections. CONCLUSIONS: These data, along with previous studies showing that the deficiency of LOX in mice or inhibition of lysyl oxidases in turkeys and rats causes aortic dissections, support the conclusion that rare genetic variants in LOX predispose to thoracic aortic disease. PMID- 26838788 TI - Resident PW1+ Progenitor Cells Participate in Vascular Remodeling During Pulmonary Arterial Hypertension. AB - RATIONALE: Pulmonary arterial hypertension is characterized by vascular remodeling and neomuscularization. PW1(+) progenitor cells can differentiate into smooth muscle cells (SMCs) in vitro. OBJECTIVE: To determine the role of pulmonary PW1(+) progenitor cells in vascular remodeling characteristic of pulmonary arterial hypertension. METHODS AND RESULTS: We investigated their contribution during chronic hypoxia-induced vascular remodeling in Pw1(nLacZ+/-) mouse expressing beta-galactosidase in PW1(+) cells and in differentiated cells derived from PW1(+) cells. PW1(+) progenitor cells are present in the perivascular zone in rodent and human control lungs. Using progenitor markers, 3 distinct myogenic PW1(+) cell populations were isolated from the mouse lung of which 2 were significantly increased after 4 days of chronic hypoxia. The number of proliferating pulmonary PW1(+) cells and the proportion of beta-gal(+) vascular SMC were increased, indicating a recruitment of PW1(+) cells and their differentiation into vascular SMC during early chronic hypoxia-induced neomuscularization. CXCR4 inhibition using AMD3100 prevented PW1(+) cells differentiation into SMC but did not inhibit their proliferation. Bone marrow transplantation experiments showed that the newly formed beta-gal(+) SMC were not derived from circulating bone marrow-derived PW1(+) progenitor cells, confirming a resident origin of the recruited PW1(+) cells. The number of pulmonary PW1(+) cells was also increased in rats after monocrotaline injection. In lung from pulmonary arterial hypertension patients, PW1-expressing cells were observed in large numbers in remodeled vascular structures. CONCLUSIONS: These results demonstrate the existence of a novel population of resident SMC progenitor cells expressing PW1 and participating in pulmonary hypertension-associated vascular remodeling. PMID- 26838790 TI - Long-Term Outcome of Administration of c-kit(POS) Cardiac Progenitor Cells After Acute Myocardial Infarction: Transplanted Cells Do not Become Cardiomyocytes, but Structural and Functional Improvement and Proliferation of Endogenous Cells Persist for at Least One Year. AB - RATIONALE: Cardiac progenitor cells (CPCs) improve left ventricular remodeling and function after acute or chronic myocardial infarction. However, the long-term (>5 weeks) effects, potential tumorigenicity, and fate of transplanted CPCs are unknown. OBJECTIVE: To assess the outcome of CPC therapy at 1 year. METHODS AND RESULTS: Female rats underwent a 90-minute coronary occlusion; 4 hours after reperfusion, they received intracoronarily vehicle or 1 million male, syngeneic CPCs. One year later, CPC-treated rats exhibited smaller scars and more viable myocardium in the risk region, along with improved left ventricular remodeling and regional and global left ventricular function. No tumors were observed. Some transplanted (Y-chromosome(POS)) CPCs (or their progeny) persisted and continued to proliferate, but they failed to acquire a mature cardiomyocyte phenotype and were too few (4-8% of nuclei) to account for the benefits of CPC therapy. Surprisingly, CPC transplantation triggered a prolonged proliferative response of endogenous cells, resulting in increased formation of endothelial cells and Y chromosome(NEG) CPCs for 12 months and increased formation, for at least 7 months, of small cells that expressed cardiomyocytic proteins (alpha-sarcomeric actin) but did not have a mature cardiomyocyte phenotype. CONCLUSIONS: The beneficial effects of CPCs on left ventricular remodeling and dysfunction are sustained for at least 1 year and thus are likely to be permanent. Because transplanted CPCs do not differentiate into mature myocytes, their major mechanism of action must involve paracrine actions. These paracrine mechanisms could be very prolonged because some CPCs engraft, proliferate, and persist at 1 year. This is the first report that transplantation of any cell type in the heart induces a proliferative response that lasts at least 1 year. The results strongly support the safety and clinical utility of CPC therapy. PMID- 26838789 TI - Mutual Regulation of Epicardial Adipose Tissue and Myocardial Redox State by PPAR gamma/Adiponectin Signalling. AB - RATIONALE: Adiponectin has anti-inflammatory effects in experimental models, but its role in the regulation of myocardial redox state in humans is unknown. Although adiponectin is released from epicardial adipose tissue (EpAT), it is unclear whether it exerts any paracrine effects on the human myocardium. OBJECTIVE: To explore the cross talk between EpAT-derived adiponectin and myocardial redox state in the human heart. METHODS AND RESULTS: EpAT and atrial myocardium were obtained from 306 patients undergoing coronary artery bypass grafting. Functional genetic polymorphisms that increase ADIPOQ expression (encoding adiponectin) led to reduced myocardial nicotinamide adenine dinucleotide phosphate oxidase-derived O2 (-), whereas circulating adiponectin and ADIPOQ expression in EpAT were associated with elevated myocardial O2 (-). In human atrial tissue, we demonstrated that adiponectin suppresses myocardial nicotinamide adenine dinucleotide phosphate oxidase activity, by preventing AMP kinase-mediated translocation of Rac1 and p47(phox) from the cytosol to the membranes. Induction of O2 (-) production in H9C2 cardiac myocytes led to the release of a transferable factor able to induce peroxisome proliferator-activated receptor-gamma-mediated upregulation of ADIPOQ expression in cocultured EpAT. Using a NOX2 transgenic mouse and a pig model of rapid atrial pacing, we found that oxidation products (such as 4-hydroxynonenal) released from the heart trigger peroxisome proliferator-activated receptor-gamma-mediated upregulation of ADIPOQ in EpAT. CONCLUSIONS: We demonstrate for the first time in humans that adiponectin directly decreases myocardial nicotinamide adenine dinucleotide phosphate oxidase activity via endocrine or paracrine effects. Adiponectin expression in EpAT is controlled by paracrine effects of oxidation products released from the heart. These effects constitute a novel defense mechanism of the heart against myocardial oxidative stress. PMID- 26838791 TI - Functional Tuning of Intrinsic Endothelial Ca2+ Dynamics in Swine Coronary Arteries. AB - RATIONALE: Recent data from mesenteric and cerebral beds have revealed spatially restricted Ca(2+) transients occurring along the vascular intima that control effector recruitment and vasodilation. Although Ca(2+) is pivotal for coronary artery endothelial function, spatial and temporal regulation of functional Ca(2+) signals in the coronary endothelium is poorly understood. OBJECTIVE: We aimed to determine whether a discrete spatial and temporal profile of Ca(2+) dynamics underlies endothelium-dependent relaxation of swine coronary arteries. METHODS AND RESULTS: Using confocal imaging, custom automated image analysis, and myography, we show that the swine coronary artery endothelium generates discrete basal Ca(2+) dynamics, including isolated transients and whole-cell propagating waves. These events are suppressed by depletion of internal stores or inhibition of inositol 1,4,5-trisphosphate receptors but not by inhibition of ryanodine receptors or removal of extracellular Ca(2+). In vessel rings, inhibition of specific Ca(2+)-dependent endothelial effectors, namely, small and intermediate conductance K(+) channels (K(Ca)3.1 and K(Ca)2.3) and endothelial nitric oxide synthase, produces additive tone, which is blunted by internal store depletion or inositol 1,4,5-trisphosphate receptor blockade. Stimulation of endothelial inositol 1,4,5-trisphosphate-dependent signaling with substance P causes idiosyncratic changes in dynamic Ca(2+) signal parameters (active sites, event frequency, amplitude, duration, and spatial spread). Overall, substance P-induced vasorelaxation corresponded poorly with whole-field endothelial Ca(2+) measurements but corresponded precisely with the concentration-dependent change in Ca(2+) dynamics (linearly translated composite of dynamic parameters). CONCLUSIONS: Our findings show that endothelium-dependent control of swine coronary artery tone is determined by spatial and temporal titration of inherent endothelial Ca(2+) dynamics that are not represented by tissue-level averaged Ca(2+) changes. PMID- 26838794 TI - Impact of Cell Therapy on Myocardial Perfusion and Cardiovascular Outcomes in Patients With Angina Refractory to Medical Therapy: A Systematic Review and Meta Analysis. AB - RATIONALE: The effect of stem/progenitor cells on myocardial perfusion and clinical outcomes in patients with refractory angina remains unclear because studies published to date have been small phase I-II trials. OBJECTIVE: We performed a meta-analysis of randomized controlled trials to evaluate the effect of cell-based therapy in patients with refractory angina who were ineligible for coronary revascularization. METHODS AND RESULTS: Several data sources were searched from inception to September 2015, which yielded 6 studies. The outcomes pooled were indices of angina (anginal episodes, Canadian Cardiovascular Society angina class, exercise tolerance, and antianginal medications), myocardial perfusion, and clinical end points. We combined the reported clinical outcomes (myocardial infarction, cardiac-related hospitalization, and mortality) into a composite end point (major adverse cardiac events). Mean difference (MD), standardized mean differences, or odds ratio were calculated to assess relevant outcomes. Our analysis shows an improvement in anginal episodes (MD, -7.81; 95% confidence interval [CI], -15.22 to -0.41), use of antianginal medications (standardized MD, -0.59; 95% CI, -1.03 to -0.14), Canadian Cardiovascular Society class (MD, -0.58; 95% CI, -1.00 to -0.16), exercise tolerance (standardized MD, 0.331; 95% CI, 0.08 to 0.55), and myocardial perfusion (standardized MD, -0.49; 95% CI, -0.76 to -0.21) and a decreased risk of major adverse cardiac events (odds ratio, 0.49; 95% CI, 0.25 to 0.98) and arrhythmias (odds ratio, 0.25; 95% CI, 0.06 to 0.98) in cell-treated patients when compared with patients on maximal medical therapy. CONCLUSIONS: The present meta-analysis indicates that cell-based therapies are not only safe but also lead to an improvement in indices of angina, relevant clinical outcomes, and myocardial perfusion in patients with refractory angina. These encouraging results suggest that larger, phase III randomized controlled trials are in order to conclusively determine the effect of stem/progenitor cells in refractory angina. PMID- 26838795 TI - Economic vulnerability to health shocks and coping strategies: evidence from Andhra Pradesh, India. AB - Empirical research has shown that households in developing countries are unable to sustain current levels of consumption during and after severe health crises due to substantial increase in medical expenditure and/or loss of income. Health events are also found to have an adverse impact on nutritional status and educational attainment of household members. Thus, in this study, we investigate: who are vulnerable to welfare loss from health shocks, what are the household responses to cope with the economic burden of health shocks and if policy responses like state health insurance schemes are effective in reducing the economic vulnerability. We use self-reported measures of health shocks and coping strategies from the longitudinal survey of the ongoing Young Lives project in India [Andhra Pradesh (AP)] to identify the characteristics of vulnerable groups and perform three-level random intercept logistic regression that takes into account contextual or environmental factors. What emerges is socioeconomic status of household (determined by education, wealth, occupation and caste/religious group) and its demographic characteristics like gender of the household head and proportion of elderly and disabled members matter for outcomes related to health events. Households adopt different strategies to cope with the economic costs of ill-health; borrowing is the most widely used strategy. For credit, majority of households rely on informal sources (moneylenders, friends, relatives, etc.) and have little or no access to formal sources. However, health shock to main breadwinner leads to households adopting costly strategies like reducing consumption or sending children to work. We found no evidence that the state health insurance scheme reduced the household welfare loss from health shocks and their coping strategies. The results suggest that health insurance schemes have to be complemented with access to micro-credit and social security schemes for self-employed persons/workers in informal sector to reduce the economic burden faced by households due to health shocks. PMID- 26838793 TI - A Large-Scale Investigation of Hypoxia-Preconditioned Allogeneic Mesenchymal Stem Cells for Myocardial Repair in Nonhuman Primates: Paracrine Activity Without Remuscularization. AB - RATIONALE: The effectiveness of transplanted bone marrow mesenchymal stem cells (MSCs) for cardiac repair has been limited; thus, strategies for optimizing stem cell-based myocardial therapy are needed. OBJECTIVE: The present study was designed to test our central hypothesis that hypoxia-preconditioned MSCs (HP MSCs) are more effective than MSCs cultured under ambient oxygen levels for the treatment of myocardial injury in a large-scale (N=49), long-term (9 months), nonhuman primate (Cynomolgous monkeys) investigation. METHODS AND RESULTS: MSCs were engineered to express green fluorescent protein, cultured under ambient oxygen or 0.5% oxygen (HP-MSCs) for 24 hours and then tested in the infarcted hearts of Cynomolgus monkeys (1*10(7) cells per heart). Hypoxia preconditioning increased the expression of several prosurvival/proangiogenic factors in cultured MSCs, and measurements of infarct size and left-ventricular function at day 90 after myocardial infarction were significantly more improved in monkeys treated with HP-MSCs than in monkeys treated with the control vehicle; functional improvements in normal cultured bone marrow mesenchymal stem cells-treated monkeys were not significant. HP-MSCs transplantation was also associated with increases in cardiomyocyte proliferation, vascular density, myocardial glucose uptake, and engraftment of the transplanted cells and with declines in endogenous cell apoptosis, but did not increase the occurrence of arrhythmogenic complications. CONCLUSIONS: Hypoxia preconditioning improved the effectiveness of MSCs transplantation for the treatment of myocardial infarction in nonhuman primates without increasing the occurrence of arrhythmogenic complications, which suggests that future clinical trials of HP-MSCs transplantation are warranted. PMID- 26838792 TI - The Expanding Complexity of Estrogen Receptor Signaling in the Cardiovascular System. AB - Estrogen has important effects on cardiovascular function including regulation of vascular function, blood pressure, endothelial relaxation, and the development of hypertrophy and cardioprotection. However, the mechanisms by which estrogen mediates these effects are still poorly understood. As detailed in this review, estrogen can regulate transcription by binding to 2 nuclear receptors, ERalpha and ERbeta, which differentially regulate gene transcription. ERalpha and ERbeta regulation of gene transcription is further modulated by tissue-specific coactivators and corepressors. Estrogen can bind to ERalpha and ERbeta localized at the plasma membrane as well as G-protein-coupled estrogen receptor to initiate membrane delimited signaling, which enhances kinase signaling pathways that can have acute and long-term effects. The kinase signaling pathways can also mediate transcriptional changes and can synergize with the ER to regulate cell function. This review will summarize the beneficial effects of estrogen in protecting the cardiovascular system through ER-dependent mechanisms with an emphasis on the role of the recently described ER membrane signaling mechanisms. PMID- 26838797 TI - DNA barcoding reveals a mysterious high species diversity of conifer-feeding aphids in the mountains of southwest China. AB - The mountains of southwest China are one of the hot spots of biodiversity in the world. However, the high-altitude fauna that inhabit these mountains remain a mystery. In this study, the species diversity of the aphids of the genus Cinara from the high-altitude coniferous forests was first assessed, and then the processes and the mechanisms of speciation were discussed. Three hundreds and four aphid samples that contained 3040 individuals were collected during fourteen field surveys. The molecular clusters derived from the DNA barcodes were used to explore the species diversity. Notably, the aphid alpha-diversity was high, with as many as 94 candidate species, and furthermore, 86.2% of the species collected had not been previously recorded. The centers of aphid species richness corresponded to the distributional pattern of the diversity of the host conifer plant species. The divergence time revealed that following the uplift of the Qinghai-Tibetan Plateau during the Pleistocene, the changes in the climate, ecology and host habitats were likely the most important factors that drove the rapid process of evolutionary radiation in the aphids. Our findings revealed the high species diversity of the aphids with DNA barcoding. PMID- 26838796 TI - Sea cucumber (Codonopsis pilosula) oligopeptides: immunomodulatory effects based on stimulating Th cells, cytokine secretion and antibody production. AB - This study aimed to investigate the immunomodulating activity of small molecule oligopeptides from sea cucumber (Codonopsis pilosula) (SOP) in mice. Seven assays were performed to determine the immunomodulatory effects, including splenic lymphocyte proliferation and delayed-type hypersensitivity assays (cell-mediated immunity), IgM antibody response of spleen to sheep red blood cells (SRBC) and serum hemolysin level assays (humoral immunity), the carbon clearance assay and the phagocytic capacity of peritoneal cavity phagocytes assay (macrophage phagocytosis), and the NK cell activity assay. Spleen T lymphocyte subpopulations, multiplex sandwich immunoassays of serum cytokine and immunoglobulin levels and enzyme-linked immunosorbent assays for small intestinal secretory immunoglobulin were performed to study the mechanism by which SOP affects the immune system. We found that SOP could improve immune functions in mice, which may be due to the enhancement of the functions of cell-mediated immunity, humoral immunity, macrophage phagocytosis and NK cell activity. From the cellular and molecular assays, we postulated that the immunomodulatory effects are most likely attributed to the stimulation of Th cells, cytokine secretion and antibody production. PMID- 26838798 TI - Angiosarcoma of the Scalp: Metastatic Pulmonary Cystic Lesions Initially Misinterpreted as Benign Findings on 18F-FDG PET/CT. AB - Angiosarcomas are rare and only represent about 2% of all soft tissue sarcomas. They arise from vascular or lymphatic endothelial cells and are most commonly located in the heart, liver, breast, and skin. Cutaneous angiosarcoma of the scalp is highly malignant and with dismal prognosis. Reported five-year survival is <30%. The mainstay of treatment is surgical resection and adjuvant radiation therapy, but failure rates following local therapy are high. Cutaneous angiosarcoma of the scalp has a predilection for pulmonary metastases with a variety of morphologic patterns on imaging. Metastatic disease in terms of pulmonary thin-walled, cystic lesions, may not be hypermetabolic on (18)F-FDG PET and, as such, could be misinterpreted as benign findings. We present a case demonstrating the diagnostic uncertainty and delay in an elderly male with angiosarcoma of the scalp presenting with metastatic lung lesions following failure of local therapy. PMID- 26838799 TI - Ultrasonography of the Kidney: A Pictorial Review. AB - Ultrasonography of the kidneys is essential in the diagnosis and management of kidney-related diseases. The kidneys are easily examined, and most pathological changes in the kidneys are distinguishable with ultrasound. In this pictorial review, the most common findings in renal ultrasound are highlighted. PMID- 26838801 TI - Economic Analysis of Alternative Strategies for Detection of ALK Rearrangements in Non Small Cell Lung Cancer. AB - Identification of alterations in ALK gene and development of ALK-directed therapies have increased the need for accurate and efficient detection methodologies. To date, research has focused on the concordance between the two most commonly used technologies, fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC). However, inter-test concordance reflects only one, albeit important, aspect of the diagnostic process; laboratories, hospitals, and payors must understand the cost and workflow of ALK rearrangement detection strategies. Through literature review combined with interviews of pathologists and laboratory directors in the U.S. and Europe, a cost-impact model was developed that compared four alternative testing strategies-IHC only, FISH only, IHC pre-screen followed by FISH confirmation, and parallel testing by both IHC and FISH. Interviews were focused on costs of reagents, consumables, equipment, and personnel. The resulting model showed that testing by IHC alone cost less ($90.07 in the U.S., $68.69 in Europe) than either independent or parallel testing by both FISH and IHC ($441.85 in the U.S. and $279.46 in Europe). The strategies differed in cost of execution, turnaround time, reimbursement, and number of positive results detected, suggesting that laboratories must weigh the costs and the clinical benefit of available ALK testing strategies. PMID- 26838802 TI - Potential Pitfalls on the (99m)Tc-Mebrofenin Hepatobiliary Scintigraphy in a Patient with Biliary Atresia Splenic Malformation Syndrome. AB - Biliary atresia (BA) is an obliterative cholangiopathy affecting 1:10.000-14.000 of newborns. Infants with Biliary Atresia Splenic Malformation syndrome (BASM) are a subgroup of BA patients with additional congenital anomalies. Untreated the disease will result in fatal liver failure within the first years of life. Kasai portoenterostomy restores bile flow and delay the progressive liver damage thereby postponing liver transplantation. An early diagnosis is of most importance to ensure the effectiveness of the operation. The (99m)Tc-Mebrofenin hepatobiliary scintigraphy is part of the diagnostic strategy when an infant presents jaundice due to conjugated hyperbilirubinemia (>20 umol/L total bilirubin of which 20% is conjugated) with its high sensitivity of 97%-100% in refuting BA. Rapid extraction of tracer by the liver and no visible tracer in the small bowl after 24 h is indicative of BA. Laparotomy with antegrade cholangiography is then performed giving the final diagnosis when the remains of the obliterated biliary tree are revealed in the case of BA. We present a case demonstrating some of the challenges of interpreting the (99m)Tc-Mebrofenin hepatobiliary scintigraphy in an infant with BASM and stress the importance that the (99m)Tc-Mebrofenin hepatobiliary scintigraphy is part of a spectrum of imaging modalities in diagnosing BA. PMID- 26838800 TI - Hepatocellular Carcinoma, Fibrolamellar Variant: Diagnostic Pathologic Criteria and Molecular Pathology Update. A Primer. AB - Fibrolamellar hepatocellular carcinoma (FL-HCC) is generally a fairly rare event in routine pathology practice. This variant of hepatocellular carcinoma (HCC) is peculiarly intriguing and,in addition, poorly understood. Young people or children are often the target individuals with this type of cancer. Previously, I highlighted some pathology aspects of FL-HCC, but in this review, the distinctive clinico-pathologic features of FL-HCC and the diagnostic pathologic criteria of FL-HCC are fractionally reviewed and expanded upon. Further, molecular genetics update data with reference to this specific tumor are particularly highlighted as a primer for general pathologists and pediatric histopathologists. FL-HCC may present with metastases, and regional lymph nodes may be sites of metastatic spread. However, peritoneal and pulmonary metastatic foci have also been reported. To the best of our knowledge, FL-HCC was initially considered having an indolent course, but survival outcomes have recently been updated reconsidering the prognosis of this tumor. Patients seem to respond well to surgical resection, but recurrences are common. Thus, alternative therapies, such as chemotherapy and radiation, are ongoing. Overall, it seems that this aspect has not been well studied for this variant of HCC and should be considered as target for future clinical trials. Remarkably, FL-HCC data seem to point to a liver neoplasm of uncertain origin and unveiled outcome. A functional chimeric transcript incorporating DNAJB1 and PRKACA was recently added to FL-HCC. This sensational result may give remarkable insights into the understanding of this rare disease and potentially provide the basis for its specific diagnostic marker. Detection of DNAJB1-PRKACA seems to be, indeed, a very sensitive and specific finding in supporting the diagnosis of FL-HCC. In a quite diffuse opinion, prognosis of this tumor should be reconsidered following the potentially mandatory application of new molecular biological tools. PMID- 26838804 TI - Interobserver and Intraobserver Reproducibility with Volume Dynamic Contrast Enhanced Computed Tomography (DCE-CT) in Gastroesophageal Junction Cancer. AB - The purpose of this study was to assess inter- and intra-observer reproducibility of three different analytic methods to evaluate quantitative dynamic contrast enhanced computed tomography (DCE-CT) measures from gastroesophageal junctional cancer. Twenty-five DCE-CT studies with gastroesophageal junction cancer were selected from a previous longitudinal study. Three radiologists independently reviewed all scans, and one repeated the analysis eight months later for intraobserver analysis. Review of the scans consisted of three analysis methods: (I) Four, fixed small sized regions of interest (2-dimensional (2D) fixed ROIs) placed in the tumor periphery, (II) 2-dimensional regions of interest (2D-ROI) along the tumor border in the tumor center, and (III) 3-dimensional volumes of interest (3D-VOI) containing the entire tumor volume. Arterial flow, blood volume and permeability (k(trans)) were recorded for each observation. Inter- and intra observer variability were assessed by Intraclass Correlation Coefficient (ICC) and Bland-Altman statistics. Interobserver ICC was excellent for arterial flow (0.88), for blood volume (0.89) and for permeability (0.91) with 3D-VOI analysis. The 95% limits of agreement were narrower for 3D analysis compared to 2D analysis. Three-dimensional volume DCE-CT analysis of gastroesophageal junction cancer provides higher inter- and intra-observer reproducibility with narrower limits of agreement between readers compared to 2D analysis. PMID- 26838803 TI - Early Dementia Screening. AB - As the population of the world increases, there will be larger numbers of people with dementia and an emerging need for prompt diagnosis and treatment. Early dementia screening is the process by which a patient who might be in the prodromal phases of a dementing illness is determined as having, or not having, the hallmarks of a neurodegenerative condition. The concepts of mild cognitive impairment, or mild neurocognitive disorder, are useful in analyzing the patient in the prodromal phase of a dementing disease; however, the transformation to dementia may be as low as 10% per annum. The search for early dementia requires a comprehensive clinical evaluation, cognitive assessment, determination of functional status, corroborative history and imaging (including MRI, FDG-PET and maybe amyloid PET), cerebrospinal fluid (CSF) examination assaying Abeta1-42, T tau and P-tau might also be helpful. Primary care physicians are fundamental in the screening process and are vital in initiating specialist investigation and treatment. Early dementia screening is especially important in an age where there is a search for disease modifying therapies, where there is mounting evidence that treatment, if given early, might influence the natural history-hence the need for cost-effective screening measures for early dementia. PMID- 26838805 TI - Domain swapping oligomerization of thermostable c-type cytochrome in E. coli cells. AB - Knowledge on domain swapping in vitro is increasing, but domain swapping may not occur regularly in vivo, and its information in cells is limited. Herein, we show that domain-swapped oligomers of a thermostable c-type cytochrome, Hydrogenobacter thermophilus cyt c552, are formed in E. coli which expresses cyt c552. The region containing the N-terminal alpha-helix and heme was domain swapped between protomers in the dimer formed in E. coli. The amount of cyt c552 oligomers increased in E. coli as the cyt c552 concentration was increased, whereas that of high-order oligomers decreased in the order of decrease in protein stability, indicating that domain swapping decreases in cells when the protein stability decreases. Apo cyt c552 was detected in the cyt c552 oligomer formed in E. coli, but not in that of the A5F/M11V/Y32F/Y41E/I76V mutant. The cyt c552 oligomer containing its apo protein may form at the periplasm, since the apo protein detected by mass measurements did not contain the signal peptide. These results show that domain-swapped cyt c552 oligomers were formed in E. coli, owing to the stability of the transient oligomer containing the apo protein before heme attachment. This is an indication that exceedingly stable proteins may have disadvantages forming domain-swapped oligomers in cells. PMID- 26838807 TI - Informant Perceptions of the Cause of Activities of Daily Living Difficulties in Parkinson's Disease. AB - OBJECTIVE: Individuals with Parkinson's disease (PD) can have difficulties with activities of daily living (ADL) that stem from cognitive, motor, or affective manifestations of the disease. Accurately attributing ADL difficulty specifically to cognitive decline is critical when conducting a neuropsychological evaluation of a person with PD. Informant description of ADL performance is frequently used for this purpose, but there has been little work assessing informants' ability to attribute ADL dysfunction to a specific symptom source in PD. METHOD: Fifty community dwelling individuals with PD completed cognitive, motor, and affective measures. A knowledgeable informant completed an ADL scale that asked about degree and perceived source of difficulty (cognitive, motor, affective) for each task. RESULTS: Informants indicated that motor dysfunction was the most common source of ADL difficulty, but the informants viewed difficulty with certain tasks, such as financial management, as particularly related to cognitive dysfunction. Informant reports of the source of ADL dysfunction (cognitive, motor, affective) were consistent with clinical measures of those specific dysfunctions. ADL dysfunction attributed to cognition specifically (chi(2) = 9.80, p = .01) was higher in those with measurable cognitive impairment. CONCLUSIONS: Informant reports of the sources of ADL dysfunction correlate with clinical measures of these symptoms, suggesting that informants may provide useful clinical information about the cause of ADL dysfunction in persons with PD. PMID- 26838808 TI - Protective effect and mechanism of action of saponins isolated from the seeds of gac (Momordica cochinchinensis Spreng.) against cisplatin-induced damage in LLC PK1 kidney cells. AB - This study was performed to investigate the renoprotective effect and mechanism of Momordicae Semen, gac seeds, against the cisplatin-induced damage in LLC-PK1 kidney cells. In order to identify the active components, three major saponins were isolated from extract of the gac seed, gypsogenin 3-O-beta-d galactopyranosyl(1->2)-[alpha-L-rhamnopyranosyl(1->3)]-beta-d-glucuronopyranoside (1), quillaic acid 3-O-beta-D-galactopyranosyl(1->2)-[alpha-L-rhamnopyranosyl(1 >3)]-beta-D-glucuronopyranoside (2), and momordica saponin I (3). Compounds 1 and 2 ameliorated cisplatin-induced nephrotoxicity up to 80% of the control value at both 5 and 25MUM. Phosphorylation of MAPKs was decreased along cisplatin treatment after treatment with compounds 1 and 2. These results show that blocking the MAPKs signaling cascade plays a critical role in mediating the renoprotective effect of Momordicae Semen extract and compounds 1 and 2. PMID- 26838806 TI - Bcl2 is a critical regulator of bile acid homeostasis by dictating Shp and lncRNA H19 function. AB - Bile acid (BA) metabolism is tightly controlled by nuclear receptor signaling to coordinate regulation of BA synthetic enzymes and transporters. Here we reveal a molecular cascade consisting of the antiapoptotic protein BCL2, nuclear receptor Shp, and long non-coding RNA (lncRNA) H19 to maintain BA homeostasis. Bcl2 was overexpressed in liver of C57BL/6J mice using adenovirus mediated gene delivery for two weeks. Hepatic overexpression of Bcl2 caused drastic accumulation of serum BA and bilirubin levels and dysregulated BA synthetic enzymes and transporters. Bcl2 reactivation triggered severe liver injury, fibrosis and inflammation, which were accompanied by a significant induction of H19. Bcl2 induced rapid SHP protein degradation via the activation of caspase-8 pathway. The induction of H19 in Bcl2 overexpressed mice was contributed by a direct loss of Shp transcriptional repression. H19 knockdown or Shp re-expression largely rescued Bcl2-induced liver injury. Strikingly different than Shp, the expression of Bcl2 and H19 was hardly detectable in adult liver but was markedly increased in fibrotic/cirrhotic human and mouse liver. We demonstrated for the first time a detrimental effect of Bcl2 and H19 associated with cholestatic liver fibrosis and an indispensable role of Shp to maintain normal liver function. PMID- 26838809 TI - Native chemical ligation at a base-labile 4-mercaptobutyrate N(alpha)-auxiliary. AB - Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. N(alpha)-auxiliaries have long been used to enable NCL beyond cysteine. However, the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. Herein, we introduce a new class of N(alpha) auxiliary which is designed for removal under mild basic conditions. The 3-N linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. The usefulness of the new auxiliary was demonstrated in the synthesis of the anti microbial C-terminal domain of Dermicidine-1L. PMID- 26838810 TI - Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful beta galactosidase inhibitors and low concentration activators of GM1-gangliosidosis related human lysosomal beta-galactosidase. AB - From an easily available partially protected formal derivative of 1 deoxymannojirimycin, by hydroxymethyl chain-branching and further elaboration, lipophilic analogs of the powerful beta-d-galactosidase inhibitor 4-epi isofagomine have become available. New compounds exhibit improved inhibitory activities comparable to benchmark compound NOEV (N-octyl-epi-valienamine) and may serve as leads towards improved and more selective pharmacological chaperones for GM1-gangliosidosis. PMID- 26838811 TI - Absence of a spin-signature from a single Ho adatom as probed by spin-sensitive tunneling. AB - Whether rare-earth materials can be used as single-atom magnetic memory is an ongoing debate in recent literature. Here we show, by inelastic and spin-resolved scanning tunnelling-based methods, that we observe a strong magnetic signal and excitation from Fe atoms adsorbed on Pt(111), but see no signatures of magnetic excitation or spin-based telegraph noise for Ho atoms. Moreover, we observe that the indirect exchange field produced by a single Ho atom is negligible, as sensed by nearby Fe atoms. We demonstrate, using ab initio methods, that this stems from a comparatively weak coupling of the Ho 4f electrons with both tunnelling electrons and substrate-derived itinerant electrons, making both magnetic coupling and detection very difficult when compared to 3d elements. We discuss these results in the context of ongoing disputes and clarify important controversies. PMID- 26838813 TI - Spectroscopic metrics allow in situ measurement of mean size and thickness of liquid-exfoliated few-layer graphene nanosheets. AB - Liquid phase exfoliation is a powerful and scalable technique to produce defect free mono- and few-layer graphene. However, samples are typically polydisperse and control over size and thickness is challenging. Notably, high throughput techniques to measure size and thickness are lacking. In this work, we have measured the extinction, absorption, scattering and Raman spectra for liquid phase exfoliated graphene nanosheets of various lateral sizes (90 <= <= 810 nm) and thicknesses (2.7 <= <= 10.4). We found all spectra to show well defined dependences on nanosheet dimensions. Measurements of extinction and absorption spectra of nanosheet dispersions showed both peak position and spectral shape to vary with nanosheet thickness in a manner consistent with theoretical calculations. This allows the development of empirical metrics to extract the mean thickness of liquid dispersed nanosheets from an extinction (or absorption) spectrum. While the scattering spectra depended on nanosheet length, poor signal to noise ratios made the resultant length metric unreliable. By analyzing Raman spectra measured on graphene nanosheet networks, we found both the D/G intensity ratio and the width of the G-band to scale with mean nanosheet length allowing us to establish quantitative relationships. In addition, we elucidate the variation of 2D/G band intensities and 2D-band shape with the mean nanosheet thickness, allowing us to establish quantitative metrics for mean nanosheet thickness from Raman spectra. PMID- 26838814 TI - Mechanical and biological properties of photocurable oligolactide-HA composites investigated under accelerated degradation. AB - The major concern related to biodegradable bone substitute materials is the loss of mechanical strength which can be undesirable when occurring too quickly before new bone formation. In this study, the multifunctional lactide oligomers having 2, 3, and 4 arms end capped with methacrylate groups were synthesized with the aim of improving the degradation properties. Their composites with hydroxyapatite (HA) were photopolymerized and subjected to accelerated degradation at 60 degrees C. The results showed that increasing number of arms significantly improved thermal and mechanical properties as well as biocompatibility of the composites. All composites although varying in number of arms had similar levels of bone-specific gene expression and calcification indicating their equal bioactivity in supporting bone formation. The high HA content in the composites was proposed to be responsible for enhanced osteoblast response, and this tended to suppress the effects of polymeric structure. PMID- 26838812 TI - Genetic regulation of salt stress tolerance revealed by RNA-Seq in cotton diploid wild species, Gossypium davidsonii. AB - Cotton is an economically important crop throughout the world, and is a pioneer crop in salt stress tolerance research. Investigation of the genetic regulation of salinity tolerance will provide information for salt stress-resistant breeding. Here, we employed next-generation RNA-Seq technology to elucidate the salt-tolerant mechanisms in cotton using the diploid cotton species Gossypium davidsonii which has superior stress tolerance. A total of 4744 and 5337 differentially expressed genes (DEGs) were found to be involved in salt stress tolerance in roots and leaves, respectively. Gene function annotation elucidated salt overly sensitive (SOS) and reactive oxygen species (ROS) signaling pathways. Furthermore, we found that photosynthesis pathways and metabolism play important roles in ion homeostasis and oxidation balance. Moreover, our studies revealed that alternative splicing also contributes to salt-stress responses at the posttranscriptional level, implying its functional role in response to salinity stress. This study not only provides a valuable resource for understanding the genetic control of salt stress in cotton, but also lays a substantial foundation for the genetic improvement of crop resistance to salt stress. PMID- 26838815 TI - Erratum: Quantitative high throughput screening using a primary human three dimensional organotypic culture predicts in vivo efficacy. PMID- 26838816 TI - Characterization and application of roxithromycin loaded cyclodextrin based nanoparticles for treatment of multidrug resistant bacteria. AB - An outbreak of infections with a high mortality rate caused by multidrug resistant (MDR) bacteria is one of the biggest health challenges globally. A class IV drug, roxithromycin (ROX), has poor solubility. In this study, ROX was first encapsulated in the cavity of each of the beta-cyclodextrin (betaCD) and hydroxypropyl-beta-cyclodextrin (HPbetaCD). Then, each of the resulting betaCD ROX inclusion complex and HPbetaCD-ROX inclusion complex were separately loaded into poly-(lactic-co-glycolic acid) (PLGA) to synthesize betaCD-ROX/PLGA and HPbetaCD-ROX/PLGA nanoparticles (NPs). Blank and ROX loaded PLGA (ROX-PLGA) NPs were also prepared. The loading efficiency of ROX is comparatively high for HPbetaCD-ROX/PLGA NPs in comparison to the betaCD-ROX/PLGA NPs and ROX-PLGA NPs. All designed formulations showed significant (P<0.0001) antibacterial activity against the selected MDR bacterial strains. In a nutshell, this study demonstrated a great therapeutic potential of the above-mentioned delivery systems for treatment of MDR bacteria. PMID- 26838817 TI - Improved osteoblasts growth on osteomimetic hydroxyapatite/BaTiO3 composites with aligned lamellar porous structure. AB - Osteoblasts growing into bone substitute is an important step of bone regeneration. This study prepared porous hydroxyapatite (HA)/BaTiO3 piezoelectric composites with porosity of 40%, 50% and 60% by ice-templating method. Effects of HA/BaTiO3 composites with different porosities, with and without polarizing treatment on adhesion, proliferation and differentiation of osteoblasts were investigated in vitro. Results revealed that cell densities of the porous groups were significantly higher than those of the dense group (p<0.05), so did the alkaline phosphate (ALP) and bone gla protein (BGP) activities. Porosity of 50% group exhibited higher ALP activity and BGP activity than those of the 40% and 60% groups. Scanning electron microscopy (SEM) observations revealed that osteoblasts adhered and stretched better on porous HA/BaTiO3 than on the dense one, especially HA/BaTiO3 with porosity of 50% and 60%. However, there was no significant difference in the cell morphology, cell densities, ALP and BGP activities between the polarized group and the non-polarized group (p>0.05). The absence of mechanical loading on the polarized samples may account for this. The results indicated that hierarchically porous HA/BaTiO3 played a favorable part in osteoblasts proliferation, differentiation and adhesion process and is a promising bone substitute material. PMID- 26838818 TI - In vitro hemocompatibility on thin ceramic and hydrogel films deposited on polymer substrate performed in arterial flow conditions. AB - Hydrogel coatings were stabilized by titanium carbonitride a-C:H:Ti:N buffer layers deposited directly onto the polyurethane (PU) substrate beneath a final hydrogel coating. Coatings of a-C:H:Ti:N were deposited using a hybrid method of pulsed laser deposition (PLD) and magnetron sputtering (MS) under high vacuum conditions. The influence of the buffer a-C:H:Ti:N layer on the hydrogel coating was analysed by means of a multi-scale microstructure study. Mechanical tests were performed at an indentation load of 5 mN using Berkovich indenter geometry. Haemocompatible analyses were performed in vitro using a blood flow simulator. The blood-material interaction was analysed under dynamic conditions. The coating fabrication procedure improved the coating stability due to the deposition of the amorphous titanium carbonitride buffer layer. PMID- 26838819 TI - Effects of polar solvents on the mechanical behavior of fish scales. AB - Fish scales are unique structural materials that serve as a form of natural armor. In this investigation the mechanical behavior of scales from the Cyprinus carpio was evaluated after exposure to a polar solvent. Uniaxial tensile and tear tests were conducted on specimens prepared from the scales of multiple fish extracted from near the head, middle and tail regions, and after exposure to ethanol for periods from 0 to 24h. Submersion in ethanol caused instantaneous changes in the tensile properties regardless of anatomical site, with increases in the elastic modulus, strength and modulus of toughness exceeding 100%. The largest increase in properties overall occurred in the elastic modulus of scales from the tail region and exceeded 200%. Although ethanol treatment had significant effect on the tensile properties, it had limited influence on the tear resistance. The contribution of ethanol to the mechanical behavior appears to be derived from an increase in the degree of interpeptide hydrogen-bonding of the collagen molecules. Spatial variations in the effects of ethanol exposure on the mechanical behavior arise from the differences in degree of mineralization and lower mineral content in scales of the tail region. PMID- 26838820 TI - Effect of in site strain on passivated property of the 316L stainless steels. AB - The effect of the strain of 316L stainless steel on its corrosion resistance in borate buffer solution was investigated by in site tensile test and the electrochemical impedance spectroscopy measurements. It was found that the corrosion resistance of the 316L stainless steel decreased with the increasing of in site strain. The lower corrosion resistance of the stainless steel during in site strain was mainly attributed to the higher doping concentration in passive film. Especially, with the increasing of in site strain, the concentrations of acceptor (i.e., cation vacancies) in the passive films significantly increased. More acceptor concentrations reduced the compactness of the passive film and its corrosion resistance. Moreover, two exponential relationships were found between in site strain and the charge transfer resistance of the passive film and between in site strain and total doping concentrations in passive film, respectively. PMID- 26838821 TI - Enhancement of entangled porous titanium by BisGMA for load-bearing biomedical applications. AB - The Bisphenol A glycidyl methacrylate (BisGMA) was used as binder to fix the free cross wire nodes in the entangled porous titanium for enhancement. The entangled titanium with 60% porosity after infiltrated with 5-20 vol.% BisGMA had the pore size in the range of 100 MUm-400 MUm. The enhanced materials with the real porosity of 40-55% exhibited the elastic modulus in the range of 0.4-1.4 GPa and the yielding strength in the range of 12.9-52.5 MPa. Such mechanical properties were comparable with those of cancellous bones, suggesting potentials for load bearing bio applications. PMID- 26838823 TI - Investigation of bioactivity, biocompatibility and thermal behavior of sol-gel silica glass containing a high PEG percentage. AB - SiO2/PEG organic-inorganic hybrid materials, which contain 60 or 70 weight percentage of PEG, were synthesized by the sol-gel technique. The materials were characterized and subjected to various tests to assess their application in the biomedical field. The evaluation of their morphology by scanning electron microscopy (SEM) confirms the homogeneity of the samples on the nanometer scale. Fourier transform infrared spectroscopy (FT-IR) indicated that the two components of the hybrids (SiO2 and PEG) are linked by hydrogen bonds. This feature makes them class I hybrids. Simultaneous thermogravimetry/differential thermal analysis (TG/DTA) was used to investigate their thermal behavior and to establish the best temperatures for their pre-treatment. The fundamental properties that a material must have to be used in the biomedical field are biocompatibility and bioactivity. The formation of a hydroxyapatite layer was observed on the hybrid surface by SEM/EDX and FTIR after soaking in simulated body fluid. This indicates that the materials are able to bond to bone tissue. Moreover, the biocompatibility of SiO2/PEG hybrids was assessed by performing WST-8 cytotoxicity tests on fibroblast cell NIH 3T3 after 24h of exposure. The cytotoxicity tests highlight that the cell viability is affected by the polymer percentage. The results showed that the synthesized materials were bioactive and biocompatible. Therefore, the results obtained are encouraging for the use of the obtained hybrids in dental or orthopedic applications. PMID- 26838822 TI - Wool fibril sponges with perspective biomedical applications. AB - Sheep's wool was used as a natural source to prepare keratin microfibril sponges for scaffolding, by disruption of the histological structure of the fibres through mild alkali treatment, followed by ultrasonication, casting and salt leaching. The wool sponges showed highly interconnected porosity (93%) and contain intrinsic sites of cellular recognition that mimic the extracellular matrix (ECM). They displayed good thermal and water stability due to the conversion of disulphide cystine bonds into shorter monosulphide lanthionine intermolecular bonds, but significantly swelled in water, because of the high hydrophilicity and porosity, with a volume increasing up to 38%. Nevertheless, sponges were stable in water without structural changes, with a neutral pH in aqueous media, and showed excellent resilience to repeated compression stresses. According to in vitro biocompatibility assays, wool fibril sponges showed a good cell adhesion and proliferation as proved by MTT, FDA assays and SEM observations. The unique structure of the cortical cell network made by wool keratin proteins with controlled-size macro-porosity suitable for cell guesting, and nutrient feeding, provides an excellent scaffold for future tissue engineering applications. PMID- 26838824 TI - Studying DEHP migration in plasticized PVC used for blood bags by coupling Raman confocal microscopy to UV spectroscopy. AB - Plasticized PVC is widely used to make medical devices such as tubing, perfusion bags and blood bags. By using confocal Raman microscopy on a PVC sheet plasticized with around 40% of di-(2-ethylhexyl)phthalate (DEHP), we propose a simple and sensitive approach to studying and understanding the diffusion of plasticizers from polymers into the surrounding media. Moreover, we sought to correlate our findings to standard measurements conducted by UV spectroscopy. This study showed differences in the concentration gradient observed due to the diffusion of the plasticizer inside a PVC sheet. We can thus follow the critical DEHP ratios that can impact the diffusion process. Water and ethanol were chosen as storage media: in ethanol, the lowest concentration of DEHP was observed at the surface resulting in the formation of a less plasticized layer near the interface; unlike ethanol, PVC sheets stored in water showed a greater concentration of DEHP on the film surface as an exudation of DEHP onto the surface. PMID- 26838825 TI - Osteogenic effect of tricalcium phosphate substituted by magnesium associated with Genderm(r) membrane in rat calvarial defect model. AB - Beta-tricalcium phosphate (beta-TCP) is one of the most widely employed bioresorbable materials for bone repair since it shows excellent biological compatibility, osteoconductivity and resorbability. The incorporation of divalent cations such as magnesium onto the beta-TCP structure (beta-TCMP) may improve the biological response to the material through the release of bioactive ions. The objective of this study was to evaluate, on a rat calvarial critical size grafting model, the bone regeneration process using beta-TCP and beta-TMCP granules by histomorphometric analysis. Results demonstrated that six months after bone grafting, the association of GBR (guided bone regeneration) using a membrane (GenDerm(r)) and granules of beta-TCP and beta-TCMP significantly improves bone repair in the treatment of critical-size defect in rat skulls, in comparison to untreated defects or GBR alone, leading to a bone level approximately four to five-fold greater than in the blood clot group. The beta TCMP+GenDerm(r) membrane group presented 40.5% of the defect area filled by newly formed bone, even at the central part of the defect, rather than only at the border, as seen in the other experimental groups. PMID- 26838826 TI - Magnesium substitution in brushite cements: Efficacy of a new biomaterial loaded with vancomycin for the treatment of Staphylococcus aureus infections. AB - Staphylococcus aureus is the most relevant pathogen associated with bone infection that sometimes appears after implant surgery, thus compromising a successful treatment. The aim of this work was to assess the effectiveness of brushite cements, doped with magnesium, as a new vancomycin carrier system against S.aureus infections. We performed an "in vitro" study to evaluate vancomycin release from the cements by measuring its antimicrobial activity against a strain of S.aureus. We have used two methods to load the cements with vancomycin: i) adsorption from a solution and ii) incorporation of the antibiotic into the solid phase during the cement synthesis. Furthermore, the compression strength of the loaded samples was measured to detect changes in the mechanical properties of the system. The "in vitro" study showed that the sustained release of vancomycin depends on the concentration of magnesium in the cement matrix. In addition, the standardized antibacterial assay revealed that the release of vancomycin from the cements may be helpful to prevent infections in bone regeneration procedures. PMID- 26838827 TI - Enhanced water-solubility and antibacterial activity of novel chitosan derivatives modified with quaternary phosphonium salt. AB - Chitosan (CS) has been widely recognized as an important biomaterial due to its good antimicrobial activity, biocompatibility and biodegradability. However, CS is insoluble in water in neutral and alkaline aqueous solution due to the linear aggregation of chain molecules and the formation of crystallinity. This is one of the key factors that limit its practical applications. Therefore, improving the solubility of CS in neutral and alkaline aqueous solution is a primary research direction for biomedical applications. In this paper, a reactive antibacterial compound (4-(2,5-Dioxo-pyrrolidin-1-yloxycarbonyl)-benzyl)-triphenyl-phosphonium bromide (NHS-QPS) was synthesized for chemical modification of CS, and a series of novel polymeric antimicrobial agents, N-quaternary phosphonium chitosan derivatives (N-QPCSxy, x=1-2,y=1-4) were obtained. The water solubilities and antibacterial activities of N-QPCSxy against Escherichia coli and Staphylococcus aureus were evaluated compare to CS. The water solubility of N-QPCSxy was all better than that of CS at neutral pH aqueous solution, particularly, N-QPCS14 can be soluble in water over the pH range of 3 to 12. The antibacterial activities of CS derivatives were improved by introducing quaternary phosphonium salt, and antibacterial activity of N-QPCSxy increases with degree of substitution. Overall, N-QPCS14 represents a novel antibacterial polymer material with good antibacterial activity, waters solubility and low cytotoxicity. PMID- 26838828 TI - Elaboration of ammonio methacrylate copolymer based spongy cationic particles via double emulsion solvent evaporation process. AB - The aim of present work is to investigate systematic study of the preparation of biodegradable particles via double emulsion solvent evaporation technique. The used formation is based on cationic ammonium methacrylate copolymer Eudragit(r) RS 100, without the use of any stabilizer. The effect of process parameters like ultra turrax(r) stirring speed and stirring time, ultrasonication time, polymer amount, and volume of outer aqueous phases on the colloidal properties of particles was investigated. All prepared dispersions were characterized in terms of size, size distribution, and electrokinetic properties, and surface morphology was investigated. PMID- 26838829 TI - Improved galvanic replacement growth of Ag microstructures on Cu micro-grid for enhanced SERS detection of organic molecules. AB - Galvanic growth of Ag nano/micro-structures on Cu micro-grid was systematically studied for surface-enhanced Raman scattering (SERS) applications. Detailed characterizations via FE-SEM and HR-TEM showed that processing parameters, (reaction time, Ag(+) concentration, and PVP addition) all substantially affect thermodynamics/kinetics of the replacement reaction to yield substrates of significantly different microstructures/homogeneities and thus varied SERS performances (sensitivity, enhancement factor, and reproducibility) of the Ag substrates in the detection of R6G analyte. PVP as an additive was shown to notably alter nucleation/growth behaviors of the Ag crystals and promote the deposition of dense and uniform Ag films of nearly monodisperse polyhedrons/nanoplates through suppressing dendrites crystallization. Under optimized synthesis (50mM of Ag(+), 30s of reaction, and 700 wt.% of PVP), Ag substrates exhibiting a high Raman signal enhancement factor of ~1.1 * 10(6) and a low relative standard deviation of ~0.13 in the repeated detection of 10 MUM R6G were obtained. The facile deposition and excellent performance reported in this work may allow the Ag microstructures to find wider SERS applications. Moreover, growth mechanisms of the different Ag nano/micro-structures were discussed based on extensive FE-SEM and HR-TEM analysis. PMID- 26838830 TI - Reproducibility of ZrO2-based freeze casting for biomaterials. AB - The processing technique of freeze casting has been intensely researched for its potential to create porous scaffold and infiltrated composite materials for biomedical implants and structural materials. However, in order for this technique to be employed medically or commercially, it must be able to reliably produce materials in great quantities with similar microstructures and properties. Here we investigate the reproducibility of the freeze casting process by independently fabricating three sets of eight ZrO2-epoxy composite scaffolds with the same processing conditions but varying solid loading (10, 15 and 20 vol.%). Statistical analyses (One-way ANOVA and Tukey's HSD tests) run upon measurements of the microstructural dimensions of these composite scaffold sets show that, while the majority of microstructures are similar, in all cases the composite scaffolds display statistically significant variability. In addition, composite scaffolds where mechanically compressed and statistically analyzed. Similar to the microstructures, almost all of their resultant properties displayed significant variability though most composite scaffolds were similar. These results suggest that additional research to improve control of the freeze casting technique is required before scaffolds and composite scaffolds can reliably be reproduced for commercial or medical applications. PMID- 26838831 TI - Vincristine sulfate loaded dextran microspheres amalgamated with thermosensitive gel offered sustained release and enhanced cytotoxicity in THP-1, human leukemia cells: In vitro and in vivo study. AB - Vincristine sulfate (VCS) is a drug of choice for the treatment of childhood and adult acute lymphocytic leukemia, Hodgkin's, non-Hodgkin's lymphoma as well as solid tumors including sarcomas. However, poor biopharmaceutical and pharmacokinetic traits of VCS like short serum half-life (12 min), high dosing frequency (1.4 mg/m(2) per week for 4 weeks) and extensive protein binding (75%) limit the clinical potential of VCS in cancer therapy. In present investigation, injectable vincristine sulfate loaded dextran microspheres (VCS-Dextran-MSs) were prepared and amalgamated with chitosan-beta-glycerophosphate gel (VCS-Dextran-MSs Gel) to surmount the biopharmaceutical and pharmacokinetic limitations of VCS that consequently induced synergistic sustained release pattern of the drug. Particle size and zeta-potential of VCS-Dextran-MSs were measured to be 6.8 +/- 2.4 MUm and -18.3 +/- 0.11 mV along with the encapsulation efficiency of about 60.4 +/- 4.5%. Furthermore, VCS-Dextran-MSs and VCS-Dextran-MSs-Gel exhibited slow release pattern and 94.7% and 95.8% of the drug was released in 72 h and 720 h, respectively. Results from cell viability assay and pharmacokinetic as well as histopathological analysis in mice indicated that VCS-Dextran-MSs-Gel offers superior therapeutic potential and higher AUClast than VCS-Dextran-MSs and drug solution. In conclusion, VCS-Dextran-MSs-Gel warrants further preclinical tumor growth study to scale up the technology. PMID- 26838832 TI - Synthesis and cytotoxicity study of magnesium ferrite-gold core-shell nanoparticles. AB - In this work, the core-magnesium ferrite (MgFe2O4) nanoparticles were prepared by hydrothermal technique. Completed gold (Au) shell coating on the surfaces of MgFe2O4 nanoparticles was obtained by varying core/shell ratios via a reduction method. Phase identification, morphological evolution, optical properties, magnetic properties and cytotoxicity to mammalian cells of these MgFe2O4 core coated with Au nanoparticles were examined by using a combination of X-ray diffraction, scanning electron microscopy, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy, UV-visible spectroscopy (UV-vis), vibrating sample magnetometry and resazurin microplate assay techniques. In general, TEM images revealed different sizes of the core-shell nanoparticles generated from various core/shell ratios and confirmed the completed Au shell coating on MgFe2O4 core nanoparticles via suitable core/shell ratio with particle size less than 100 nm. The core-shell nanoparticle size and the quality of coating influence the optical properties of the products. The UV-vis spectra of complete coated MgFe2O4-Au core-shell nanoparticles exhibit the absorption bands in the near-Infrared (NIR) region indicating high potential for therapeutic applications. Based on the magnetic property measurement, it was found that the obtained MgFe2O4-Au core-shell nanoparticles still exhibit superparamagnetism with lower saturation magnetization value, compared with MgFe2O4 core. Both of MgFe2O4 and MgFe2O4-Au core-shell also showed in vitro non-cytotoxicity to mouse areola fibroblast (L-929) cell line. PMID- 26838833 TI - New method of synthesis and in vitro studies of a porous biomaterial. AB - Biomaterials for bone reconstruction represent a widely studied area. In this paper, a new method of synthesis of a porous glass-ceramic obtained by thermal treatment is presented. The prepared biomaterial was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and induced couple plasma optical emission spectroscopy (ICP-OES), mercury porosimetry and by the Archimedes method. In vitro evaluations in a simulated body fluid (SBF) and in contact with SaOS2 human osteoblasts were also carried out. The porous glass ceramic is composed of a total porous network of 60% suitable for body fluid and cell infiltration, with pore sizes varying from 60 nm to 143 MUm. The presence of two crystalline phases decreases the kinetic of bioactivity compared to an amorphous biomaterial (bioactive glass). A hydroxyapatite layer appears from 15 days of immersion on the surface and inside the pores, showing a biodegradation and a bioactivity in four steps. Cytotoxicity assessments present an increase of the cellular viability after 72 h proving the non-cytotoxic effect of the glass ceramic. Thus, the results of these different studies indicate that the porous biomaterial may have a potential application for the bone regeneration. This paper also presents the novelty of this method. It is a rapid synthesis which combines simplicity and low cost. This represents an advantage for an eventual industrialization. PMID- 26838834 TI - Surface modifications and Nano-composite coatings to improve the bonding strength of titanium-porcelain. AB - Surface modifications of Ti and nano-composite coatings were employed to simultaneously improve the surface roughness, corrosion resistance and chemical bonding between porclain-Ti. The specimens were studied by field-emission scanning electron microscopy, surface roughness, differential scanning calorimetry, Fourier transform infrared spectroscopy, corrosion resistance and bonding strength tests. The SEM results showed that hybrid structures with micro stripes, nano-pores and nano-protuberances were prepared by surface modification of Ti, which significantly enhanced the surface roughness and corrosion resistance of Ti. Porous nano-composite coatings were synthesized on Ti anodized with pre-treatment in 40% HF acid. TiO2 nanoparticles were added into the hybrid coating to increase the solid phase content of the sols and avoid the formation of microcracks. With the TiO2 content increasing from 45 wt% to 60 wt%, the quantities of the microcracks on the coating surface gradually decreased. The optimal TiO2 content for the nanocomposite coatings is 60 wt% in this research. Compared to the uncoated group, the bonding strength of the coated groups showed a bonding strength improvement of 23.96%. The cytotoxicity of the 4# coating group was ranked as zero, which corresponds to non-cytotoxicity. PMID- 26838835 TI - Functionalized beta-cyclodextrin based potentiometric sensor for naproxen determination. AB - Potentiometric sensors based on neutral beta-cyclodextrins: (2-hydroxypropyl) beta-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin, heptakis(2,3,6 tri-O-benzoyl)-beta-cyclodextrin and anionic beta-cyclodextrin: (2-hydroxy-3 N,N,N-trimethylamino)propyl-beta-cyclodextrin chloride for naproxen are described. Inclusion complexes of naproxen with the above-mentioned cyclodextrins were studied using IR spectroscopy. The electrode surface was made from PVC membranes doped with the appropriate beta-cyclodextrin as ionophores and quaternary ammonium chlorides as positive charge additives that were dispersed in plasticizers. The optimum membrane contains heptakis(2,3,6-tri-O-benzoyl)-beta cyclodextrin, o-nitrophenyloctyl ether and tetraoctyl ammonium chloride as a lipophilic salt. The electrode is characterized by a Nernstian response slope of 59.0 +/- 0.5 mV decade(-1) over the linear range of 5.0 * 10(-5)-1.0 * 10(-2) mol L(-1) and the detection limit 1.0 * 10(-5) mol L(-1), as well as the response time 10s. It can be used in the pH range 6.2-8.5 for 10 months without any considerable deterioration. Incorporation of beta-cyclodextrins improved the electrode selectivity towards naproxen ions from several inorganic and organic interferents and some common drug excipients due to concovalent interactions (host molecule-guest molecule). The notable advantages of the naproxen-selective electrode include its high sensitivity, high selectivity, cost-effectiveness as well as accurate and comfortable application in drug analysis and milk samples. PMID- 26838836 TI - Temperature and magnetism bi-responsive molecularly imprinted polymers: Preparation, adsorption mechanism and properties as drug delivery system for sustained release of 5-fluorouracil. AB - Temperature and magnetism bi-responsive molecularly imprinted polymers (TMMIPs) based on Fe3O4-encapsulating carbon nanospheres were prepared by free radical polymerization, and applied to selective adsorption and controlled release of 5 fluorouracil (5-FU) from an aqueous solution. Characterization results show that the as-synthesized TMMIPs have an average diameter of about 150 nm with a typical core-shell structure, and the thickness of the coating layer is approximately 50 nm. TMMIPs also displayed obvious magnetic properties and thermo-sensitivity. The adsorption results show that the prepared TMMIPs exhibit good adsorption capacity (up to 96.53 mg/g at 25 degrees C) and recognition towards 5-FU. The studies on 5-FU loading and release in vitro suggest that the release rate increases with increasing temperature. Meanwhile, adsorption mechanisms were explored by using a computational analysis to simulate the imprinted site towards 5-FU. The interaction energy between the imprinted site and 5-FU is -112.24 kJ/mol, originating from a hydrogen bond, Van der Waals forces and a hydrophobic interaction between functional groups located on 5-FU and a NIPAM monomer. The electrostatic potential charges and population analysis results suggest that the imprinted site of 5-FU can be introduced on the surface of TMMIPs, confirming their selective adsorption behavior for 5-FU. PMID- 26838837 TI - Adhesion behaviors of Escherichia coli on hydroxyapatite. AB - Optimum design of support materials for microorganisms is required for the construction of bioreactors. However, the effects of support materials on microorganisms are still unclear. In this study, we investigated the adhesion behavior of Escherichia coli (E. coli) on hydroxyapatite (HA), polyurethane (PU), poly(vinyl chloride) (PVC), and carbon (Carbon) to obtain basic knowledge for the design of support materials. The total metabolic activity and number of E. coli adhering on the samples followed the order of HA ~ Carbon>PVC>PU. On the other hand, the water contact angle of the pellet surfaces followed the order of HA recrystallization texture in Ti-Nb Al biomedical shape memory alloy. AB - The rolling rate (r) dependence of textures was investigated in the Ti-26Nb-3Al (mol%) alloy to reveal the conditions required to form the {001}<110> recrystallization texture, which is a desirable orientation for the beta-titanium shape memory alloy. {001}<110> was the dominant cold-rolling texture when r=90% and it was transferred to the recrystallization texture without forming {112}<110>, which is detrimental for the isotropic mechanical properties of the rolled sheet. A further increase in r resulted in the formation of {112}<110> in both rolling and recrystallization textures. Therefore, r should be controlled to form only the {001}<110> rolling texture, because the {112}<110> texture can overwhelm the {001}<110> texture during recrystallization. PMID- 26838878 TI - A sensitive DNA biosensor fabricated from gold nanoparticles and graphene oxide on a glassy carbon electrode. AB - A sensitive electrochemical DNA biosensor was developed for Helicobacter pylori (H. pylori) detection using differential pulse voltammetry. Single-stranded DNA probe was immobilized on a graphene oxide/gold nanoparticles modified glassy carbon electrode (GO/AuNPs/GCE). A hybridization reaction was conducted with the target DNA and the immobilized DNA on the electrode surface. Oracet blue (OB) was selected for the first time as a redox indicator for amplifying the electrochemical signal of DNA. Enhanced sensitivity was achieved through combining the excellent electric conductivity of GO/AuNPs and the electroactivity of the OB. The DNA biosensor displayed excellent performance to demonstrate the differences between the voltammetric signals of the OB obtained from different hybridization samples (non-complementary, mismatch and complementary DNAs). The proposed biosensor has a linear range of 60.0-600.0 pM and a detection limit of 27.0 pM for detection of H. pylori. In addition, the biosensor have responded very well in the simulated real sample evaluations, signifying its potential to be used in future clinical detection of the H. pylori bacteria. PMID- 26838879 TI - Porous biodegradable EW62 medical implants resist tumor cell growth. AB - Magnesium alloys have been widely investigated for biodegradable medical applications. However, the shielding of harmful cells (eg. bacteria or tumorous cells) from immune surveillance may be compounded by the increased porosity of biodegradable materials. We previously demonstrated the improved corrosion resistance and mechanical properties of a novel EW62 (Mg-6%Nd-2%Y-0.5%Zr)) magnesium alloy by rapid solidification followed by extrusion (RS) compared to its conventional counterpart (CC). The present in vitro study evaluated the influence of rapid solidification on cytotoxicity to murine osteosarcoma cells. We found that CC and RS corrosion extracts significantly reduced cell viability over a 24-h exposure period. Cell density was reduced over 48 h following direct contact on both CC and RS surfaces, but was further reduced on the CC surface. The direct presence of cells accelerated corrosion for both materials. The corroded RS material exhibited superior mechanical properties relative to the CC material. The data show that the improved corrosion resistance of the rapidly solidified EW62 alloy (RS) resulted in a relatively reduced cytotoxic effect on tumorous cells. Hence, the tested alloy in the form of a rapidly solidified substance may introduce a good balance between its biodegradation characteristics and cytotoxic effect towards cancerous and normal cells. PMID- 26838880 TI - Strontium-doped calcium polyphosphate/ultrahigh molecular weight polyethylene composites: A new class of artificial joint components with enhanced biological efficacy to aseptic loosening. AB - To enhance implant stability and prolong the service life of artificial joint component, a new approach was proposed to improve the wear resistance of artificial joint component and endow artificial joint component with the biological efficacy of resistance to aseptic loosening. Strontium calcium polyphosphate (SCPP) were interfused in ultrahigh molecular weight polyethylene (UHMWPE) by a combination of liquid nitrogen ball-milling and flat-panel curing process to prepare the SCPP/UHMWPE composites. The micro-structure, mechanical characterization, tribological characterization and bioactivities of various SCPP/UHMWPE composites were investigated. The results suggested that this method could statistically improve the wear resistance of UHMWPE resulting from a good SCPP particle dispersion. Moreover, it is also observed that the SCPP/UHMWPE composites-wear particles could promote the production of OPG by osteoblasts and decrease the production of RANKL by osteoblasts, and then increase the OPG/RANKL ratio. This indicated that the SCPP/UHMWPE composites had potential efficacy to prevent and treat aseptic loosening. Above all, the SCPP/UHMWPE composites with a suitable SCPP content would be the promising materials for fabricating artificial joint component with ability to resist aseptic loosening. PMID- 26838881 TI - Poly (caprolactone) microparticles and chitosan thermogels based injectable formulation of etoricoxib for the potential treatment of osteoarthritis. AB - This study aimed to evaluate Poly (caprolactone) microparticles (MPs) loaded composite injectable Chitosan gel (CICGs) as a dual purpose (visco-supplement and intra articular drug delivery depot) therapeutic agent for the treatment of Osteoarthritis. Etoricoxib (COX-2 inhibitor), a highly hydrophobic drug was chosen as a model drug for the study. When administered orally, Etoricoxib poses severe cardiovascular toxicity issues. So, we have attempted to deliver this drug intra-articularly, which could retain the drug longer in the joint region and thus could ameliorate these toxicity issues. CICGs were prepared by dispersing MPs in the chitosan-Ammonium hydrogen phosphate solution and incubated at 37 degrees C. Rheology studies proved that gels were stable and had visco-elastic properties comparable to that of existing visco-supplements. The in vitro drug release profiles of CICGs were found to be more controlled when compared to MPs and bare chitosan gel (BCGs). In vitro and in vivo biocompatibility studies proved that the gels were biocompatible. In vivo synovial drug clearance studies proved that CICGs had a better drug retention capacity than BCGs and MPs. In vivo fluorescence imaging results confirmed that CICGs could stay longer in the joint region when compared to BCGs and MPs. Thus this novel CICGs could be a potential dual purpose gel for the treatment of diseased joint regions especially for Osteoarthritis. PMID- 26838882 TI - Lysozyme loading and release from Se doped hydroxyapatite nanoparticles. AB - Element-substituted hydroxyapatite (HA) based nanocomposites have become a promising therapeutic material for improving bone defect repair. Selenium substituted HA nanoparticles can both induce apoptosis of bone tumor cells and enhance osteointegration. However, the effect of selenite ions on the proteins in combination with the HA nanoparticles remains to be elucidated. Here, we investigated the influence of selenium doping concentration on the loading and release of lysozyme (LSM) as a model protein drug. The selenium substituted HA LSM composites with different doping concentrations were synthesized and characterized. The subsequent delivery of lysozyme was studied in a phosphate buffer solution (PBS). We found that selenium substituted HA-LSM composites with Se:P=10% showed the highest amount of lysozyme loading (41.7%), whereas the amount of lysozyme loaded in undoped HA nanoparticles was the lowest (34.1%). The doped selenium interacts with lysozyme molecules, which leads to the increase of beta-sheet and unordered, and the decrease of self-association, alpha-helix and beta-turns in protein structures. Moreover, selenium addition significantly slows the protein release from HA-LSM composites. The composites with Se:P=10% release lysozyme at the slightly slower rate among the samples with different Se doping concentrations. It also shows that the released lysozyme retains most of its enzymatic activity. PMID- 26838883 TI - A new and economic approach to synthesize and fabricate bioactive diopside ceramics using a modified domestic microwave oven. Part 2: effect of P2O5 additions on diopside bioactivity and mechanical properties. AB - In this work, diopside based ceramics was obtained by solid state reaction using conventional sintering (CS) and microwave sintering (MS). Moreover, different amounts of P2O5 (0.5-5.0 wt.%) have been added. It has been found that a relative density up to 95% theoretical was obtained for diopside containing 2.0 and 5.0 wt.% P2O5, sintered at 1250 degrees C for 2h and at 1075 degrees C only for 15 min using CS and MS. Excellent values of micro hardness (7.4 +/- 0.1 GPa) and 3 point flexural strength (about 270 MPa) for samples containing 5 wt.% P2O5, sintered at 1075 degrees C for 15 min using MS were measured. Besides this, a relatively low weight loss ratio has been measured (0.01%) for diopside samples containing 5 wt.% P2O5, sintered under the same conditions, after soaking in physiological salt solution for 2 days. Additionally, the bioactivity of diopside by the possibility of formation of apatite on the surface of pure diopside and diopside containing 2 wt.% of P2O5 immersed in simulated body fluid (SBF) was also confirmed. Finally, particular nano-sized of Carbonated hydroxyapatite (CHA) crystals (rice shaped) were formed and covered the surface of these samples, soaked in SBF solution for 14 days. PMID- 26838884 TI - In vitro degradation behavior of Fe-20 Mn-1.2C alloy in three different pseudo physiological solutions. AB - High manganese austenitic steels such as Fe-20Mn-1.2C alloys are among the most promising candidates for biodegradable stents applications due to their high strength, high ductility and their chemical composition. In the current work, 14 day static in-vitro tests were performed in controlled atmosphere to assess the degradation behavior in three common pseudo-physiological solutions, i.e. commercial Hanks' (CH), modified Hanks' (MH) and albumin-enriched Dulbecco's modified phosphate buffered saline (DPBS) solutions. The degraded samples surfaces as well as the degradation products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Degradation of material and degradation products are shown to be strongly dependent on the test medium due to the presence of different ionic species such as HCO3(-), CO3(2-), Cl(-), Ca(2+) or phosphate groups. In both MH and CH solutions, the increased content of HCO3(-) ions seems to promote MnCO3 crystal growth on sample surfaces whereas the presence of albumin and high content of phosphate ions promotes the formation of an amorphous layer rich in phosphates, iron and manganese. PMID- 26838885 TI - Biocompatibility of new Ti-Nb-Ta base alloys. AB - beta-type titanium alloys are promising materials in the field of medical implants. The effect of beta-phase stability on the mechanical properties, corrosion resistance and cytotoxicity of a newly designed beta-type (Ti77Nb17Ta6) biocompatible alloys are studied. The beta-phase stability was controlled by the addition of small quantities of Fe and O. X-ray diffraction and microstructural analysis showed that the addition of O and Fe stabilized the beta-phase in the treated solution condition. The strength and hardness have increased with the increase in beta-phase stability while ductility and Young's modulus have decreased. The potentio-dynamic polarization tests showed that the corrosion resistance of the new alloys is better than Ti-6Al-4V alloy by at least ten times. Neutral red uptake assay cytotoxicity test showed cell viability of at least 95%. The new alloys are promising candidates for biomedical applications due to their high mechanical properties, corrosion resistance, and reduced cytotoxicity. PMID- 26838886 TI - Interaction of dinuclear cadmium(II) 5-Cl-salicylaldehyde complexes with calf thymus DNA. AB - Five dinuclear Cd(II) complexes with the anion of 5-Cl-salicylaldehyde (5-Cl saloH) were synthesized in the absence or presence of the alpha-diimines: 2,2' bipyridine (bipy), 1,10-phenanthroline (phen), 2,9-dimethyl-1,10-phenanthroline (neoc) or 2,2'-dipyridylamine (dpamH) and characterized as [Cd(5-Cl salo)2(CH3OH)]2 (1), [Cd(5-Cl-salo)2(bipy)]2 (2), [Cd(5-Cl-salo)2(phen)]2 (3), [Cd(5-Cl-salo)(neoc)(ONO2)]2 (4) and [Cd(5-Cl-salo)(dpamEta)(ONO2)]2 (5). The complexes were characterized by spectroscopic techniques (IR, UV-vis, (1)H-NMR and (13)C-NMR), elemental analysis and molar conductivity measurements. The structures of four complexes (1-3 and 5) were determined by X-ray crystallography, providing all three possible coordination modes of the ligand 5 Cl-salicylaldehyde, i.e. bidentate or tridentate chelating and/or bridging mode. The complexes bind to calf-thymus (CT) DNA mainly by intercalation, as concluded by the viscosity measurements and present relatively high DNA-binding constants. The complexes exhibit significant ability to displace ethidium bromide (EB) from the EB-DNA complex, thus indirectly proving the intercalation as the most possible binding mode to CT DNA. PMID- 26838887 TI - Efficacy of transdermal magnesium ascorbyl phosphate delivery after ultrasound treatment with microbubbles in gel-type surrounding medium in mice. AB - Liquid microemulsions appropriate for topical application were obtained by increasing their viscosity through the addition of thickening agents. The present study first assessed the usefulness of ultrasound (US) plus US contrast agent, microbubbles (MBs), in agarose gel for enhancing transdermal drug delivery. The effect of US plus MBs in agarose gel on the penetration of the skin by magnesium ascorbyl phosphate (MAP) was explored both in vitro and in vivo. In the in vitro experiments, the stability of MBs was investigated by examining the penetration of MAP by the model drug, Evans blue, in two media: an agarose phantom and pig skin. The penetration depth in the agarose phantom and pig skin increased by 40% and 195%, respectively, when treated with US plus MBs in 0.1% agarose solution combined with MAP (UMB1), and by 48% and 206%, respectively, when treated with US plus MBs in 0.15% agarose solution and MAP (UMB2). The skin-whitening effects in C57BL/6J mice in the UMB1 and UMB2 groups over a 4-week experimental period were significantly increased by 63% and 70%, respectively, in the fourth week. The findings of this study suggest that the survival of MBs with US is affected by the viscosity of the surrounding medium, and that in mice, treatment with US plus MBs in a suitable agarose gel can increase skin permeability and enhance transdermal MAP delivery. PMID- 26838888 TI - Fabrication of an electrochemical nanoaptasensor based on AuNPs for ultrasensitive determination of cocaine in serum sample. AB - Herein we describe an ultrasensitive electrochemical nanoaptasensor for the detection of one of the most dangerous narcotic drugs available, cocaine. The nanoaptasensor was constructed by the covalent attachment of a 5'-NH2-3'-gold nanoparticles terminated aptamer on the surface of a glassy carbon electrode which was deposited with gold nanoparticles (AuNPs/GCE). It is worth noting that the interaction of the cysteamine stable self-assembled monolayer on the AuNPs/GCE surface and the covalent attachment of terephthalaldehyde via amide coupling with the amine groups in the cysteamine and aptamer, respectively, resulted in the covalent attachment of the aptamer to AuNPs/GCE. The presence of gold nanoparticles both on surface of the glassy carbon electrode and in the end of the aptamer, can provide advantages such as increase of active surface area, high acceleration of the electron transfer and improved electrochemical signal, respectively. The decrease in the peak current of [Fe(CN)6](3-/4-) as the probe redox with increase of cocaine concentration, in differential pulse voltammetry as the measuring technique, from 5 pM up to 5 nM was linear and an unprecedented detection limit of 0.5pM was yielded. Furthermore, the effect of some common analgesic drugs as the potential interferents were investigated and also, to evaluate practical application of the proposed nanoaptasensor human blood serum sample as a real sample was used. Simple preparation, low operation cost, speed and validity are the decisive factors of this method motivating its application to biosensing investigation. PMID- 26838889 TI - A novel EIS field effect structures coated with TESUD-PPy-PVC dibromoaza[7]helicene matrix for potassium ions detection. AB - In this work, we describe the development of new Aza[7]helicene-containing PVC based membranes for the K(+) ions quantification. Here, silicon nitride-based structures (Si-p/SiO2/Si3N4) were developed and the surface was activated, functionalized with an aldehyde-silane (11-(Triethoxysilyl)undecanal (TESUD)), functionalized with polypyrrole (PPy), and coated with the polyvinylchloride (PVC)-membrane containing the Aza[7]helicene as ionophore. All stages of functionalization process have been thoroughly studied by contact angle measurements (CAMs) and atomic force microscopy (AFM). The developed ion selective electrode (ISE) was then applied using electrochemical impedance spectroscopy (EIS) for the detection of potassium ions. A linear range was observed between 1.0 * 10(-8) M to 1.0 * 10(-3) M and a detection limit of 1.0 * 10(-8) M was observed. The EIS results have showed a good sensitivity to potassium ion using this novel technique. The target helicene exhibited good solubility and excellent thermal stability with a high decomposition temperature (Td > 300 degrees C) and it indicates that helicene may be a promising material as ionophore for ion-selective electrodes (ISEs) elaboration. PMID- 26838891 TI - Biological evaluation of nanosilver incorporated cellulose pulp for hygiene products. AB - Cellulose pulp has a visible market share in personal hygiene products such as sanitary napkins and baby diapers. However it offers good surface for growth of microorganisms. Huge amount of research is going on in developing hygiene products that do not initiate microbial growth. The objective of the present work is to produce antibacterial cellulose pulp by depositing silver nanopowder on the cellulose fiber. The silver nanoparticles used were of less than 100 nm in size and were characterised using transmission electron microscopy and X-ray powder diffraction studies. Antibacterial activity of the functionalized cellulose pulp was proved by JIS L 1902 method. The in-vitro cytotoxicity, in-vivo vaginal irritation and intracutaneous reactivity studies were done with silver nanopowder incorporated cellulose pulp for introducing a new value added product to the market. Cytotoxicity evaluation suggested that the silver nanoparticle incorporated cellulose pulp is non-cytotoxic. No irritation and skin sensitization were identified in animals tested with specific extracts prepared from the test material in the in-vivo experiments. The results indicated that the silver nanopowder incorporated cellulose pulp meets the requirements of the standard practices recommended for evaluating the biological reactivity and has good biocompatibility, hence can be classified as a safe hygiene product. PMID- 26838890 TI - Co-encapsulation of multi-lipids and polymers enhances the performance of vancomycin in lipid-polymer hybrid nanoparticles: In vitro and in silico studies. AB - Nano-drug delivery systems are being widely explored to overcome the challenges with existing antibiotics to treat bacterial infections [1]. Lipid-polymer hybrid nanoparticles (LPNs) display unique advantages of both liposomes and polymeric nanoparticles while excluding some of their limitations, particularly the structural integrity of the polymeric particles and the biomimetic properties of the liposome [1]. The use of helper lipids and polymers in LPNs has not been investigated, but has shown potential in other nano-drug delivery systems to improve drug encapsulation, antibacterial activity and drug release. Therefore, LPNs using co-excipients were prepared using vancomycin (VCM), glyceryl triplamitate and Eudragit RS100 as the drug, lipid and polymer respectively. Oleic acid (OA), Chitosan (CHT) and Sodium alginate (ALG) were explored as co excipients. Results indicated rod-shaped LPNs with suitable size, PDI and zeta potential, while encapsulation efficiency (%EE) increased from 27.8% to 41.5%, 54.3% and 69.3% with the addition of OA, CHT and ALG respectively. Drug release indicated that VCM-CHT had the best performance in sustained drug release of 36.1 +/- 5.35% after 24h. The EE and drug release were further corroborated by in silico and release kinetics data. In vitro antibacterial studies of all formulations exhibited better activity against bare VCM and sustained activity up to day 5 against both Staphylococcus aureus and MRSA, with VCM-OA and VCM-CHT showing better activity against MRSA. Therefore, this LPN proves to be a promising system for delivery of VCM as well as other antibiotics. PMID- 26838892 TI - A new kinetic-mechanistic approach to elucidate electrooxidation of doxorubicin hydrochloride in unprocessed human fluids using magnetic graphene based nanocomposite modified glassy carbon electrode. AB - A novel magnetic nanocomposite was synthesized in one step using polymerization of magnetic graph oxide grafted with chlorosulfonic acid (Fe3O4-GO-SO3H) in the presence of polystyrene. The prepared magnetic nanocomposite was characterized using transmission electron microscopy (TEM), dynamic differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), (Thermo gravimetric/differential thermal analysis (DTA)), Fourier transform infrared (FTIR), and UV-Vis techniques. Magnetic nanocomposite was casted on the surface of the glassy carbon electrode (PS/Fe3O4-GO-SO3H/GCE) and used for the detection and determination of doxorubicin hydrochloride (DOX) in human biological fluids. The cyclic voltammograms (CVs) of the modified electrode in aqueous solution displayed a pair of well-defined, stable and irreversible reductive/oxidation redox systems. CV study indicated that the oxidation process is irreversible and adsorption controlled. In addition, CV results indicated that DOX is oxidized via two electrons and three protons which is an unusual approach for the oxidation of DOX. A sensitive and time-saving procedure was developed for the analysis of DOX in plasma, cerebrospinal fluid, and urine with detection limit of 4.9 nM, 14 nM and 4.3 nM, respectively. PMID- 26838893 TI - Prediction of the "in vivo" mechanical behavior of biointegrable acrylic macroporous scaffolds. AB - This study examines a biocompatible scaffold series of random copolymer networks P(EA-HEA) made of Ethyl Acrylate, EA, and 2-Hydroxyl Ethyl Acrylate, HEA. The P(EA-HEA) scaffolds have been synthesized with varying crosslinking density and filled with a Poly(Vinyl Alcohol), PVA, to mimic the growing cartilaginous tissue during tissue repair. In cartilage regeneration the scaffold needs to have sufficient mechanical properties to sustain the compression in the joint and, at the same time, transmit mechanical signals to the cells for chondrogenic differentiation. Mechanical tests show that the elastic modulus increases with increasing crosslinking density of P(EA-HEA) scaffolds. The water plays an important role in the mechanical behavior of the scaffold, but highly depends on the crosslinking density of the proper polymer. Furthermore, when the scaffold with hydrogel is tested it can be seen that the modulus increases with increasing hydrogel density. Even so, the mechanical properties are inferior than those of the scaffolds with water filling the pores. The hydrogel inside the pores of the scaffolds facilitates the expulsion of water during compression and lowers the mechanical modulus of the scaffold. The P(EA-HEA) with PVA shows to be a good artificial cartilage model with mechanical properties close to native articular cartilage. PMID- 26838894 TI - Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent. AB - In this study, we prepared macromolecular MR T1 contrast agent: pullulan conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd(3+), chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd(3+) in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd(3+) incubated with Ca(2+) was performed by using a dialysis membrane (MWCO 100-500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd(3+), the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd(3+) were released from Gd-DTPA-Pullulan after 2h incubation with Ca(2+) and Fe(2+), respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t1/2,alpha=0.43 h, t1/2,beta=2.32 h), much longer than 0.11h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast. PMID- 26838895 TI - Naproxen conjugated mPEG-PCL micelles for dual triggered drug delivery. AB - A conjugate of the NSAIDs drug, naproxen, with diblock methoxy poly(ethylene glycol)-poly(epsilon-caprolactone) (mPEG-PCL) copolymer was synthesized by the reaction of copolymer with naproxen in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The naproxen conjugated copolymers were characterized with different techniques including (1)HNMR, FTIR, and DSC. The naproxen conjugated mPEG-PCL copolymers were self-assembled into micelles in aqueous solution. The TEM analysis revealed that the micelles had the average size of about 80 nm. The release behavior of conjugated copolymer was investigated in two different media with the pH values of 7.4 and 5.2. In vitro release study showed that the drug release rate was dependant on pH as it was higher at lower pH compared to neutral pH. Another feature of the conjugated micelles was a more sustained release profile compared to the conjugated copolymer. The kinetic of the drug release from naproxen conjugated micelles under different values of pH was also investigated by different kinetic models such as first-order, Makoid Banakar, Weibull, Logistic, and Gompertz. PMID- 26838896 TI - Stable non-covalent labeling of layered silicate nanoparticles for biological imaging. AB - Layered silicate nanoparticles (LSN) are widely used in industrial applications and consumer products. They also have potential benefits in biomedical applications such as implantable devices and for drug delivery. To study how nanomaterials interact with cells and tissues, techniques to track and quantify their movement through different biological compartments are essential. While radiolabels can be very sensitive, particularly for in vivo studies, fluorescent labeling has been preferred in recent years because of the array of methods available to image and quantify fluorescent nanoparticles. However, labeling can be problematic, especially if it alters the physical properties of the nanomaterial. Herein is described a novel non-covalent labeling technique for LSN using readily available fluorescent dimeric cyanine dyes without the need to use excess amounts of dye to achieve labeling, or the need for removal of unbound dye. The approach utilizes the cationic binding properties of layered silicate clays and the multiple quaternary nitrogens associated with the dyes. Preparation of YOYO-1 labeled LSN with optimal dispersion in aqueous media is presented. The utilization of the labeled particles is then demonstrated in cell binding and uptake studies using flow cytometry and confocal microscopy. The labeled LSN are highly fluorescent, stable and exhibit identical physical properties with respect to the unlabeled nanoparticles. The general approach described here is applicable to other cyanine dyes and may be utilized more widely for labeling nanoparticles that comprise a crystalline plate structure with a high binding capacity. PMID- 26838897 TI - Hydroxypropyl-beta-cyclodextrin-graphene oxide conjugates: Carriers for anti cancer drugs. AB - A novel drug carrier based on hydroxypropyl-beta-cyclodextrin (HP-beta-CD) modified carboxylated graphene oxide (GO-COOH) was designed to incorporate anti cancer drug paclitaxel (PTX). The formulated nanomedicines were characterized by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM). Results showed that PTX can be incorporated into GO-COO-HP-beta-CD nanospheres successfully, with an average diameter of about 100 nm. The solubility and stability of PTX-loaded GO-COO-HP-beta-CD nanospheres in aqueous media were greatly enhanced compared with the untreated PTX. The results of hemolysis test demonstrated that the drug-loaded nanospheres were qualified with good blood compatibility for intravenous use. In vitro anti-tumor activity was measured and results demonstrated that the incorporation of PTX into the newly developed GO COO-HP-beta-CD carrier could confer significantly improved cytotoxicity to the nanosystem against tumor cells than single application of PTX. GO-COO-HP-beta-CD nanospheres may represent a promising formulation platform for a broad range of therapeutic agent, especially those with poor solubility. PMID- 26838898 TI - Submicron magnetic core conducting polypyrrole polymer shell: Preparation and characterization. AB - Magnetic particles are of great interest in various biomedical applications, such as, sample preparation, in vitro biomedical diagnosis, and both in vivo diagnosis and therapy. For in vitro applications and especially in labs-on-a-chip, microfluidics, microsystems, or biosensors, the needed magnetic dispersion should answer various criteria, for instance, submicron size in order to avoid a rapid sedimentation rate, fast separations under an applied magnetic field, and appreciable colloidal stability (stable dispersion under shearing process). Then, the aim of this work was to prepare highly magnetic particles with a magnetic core and conducting polymer shell particles in order to be used not only as a carrier, but also for the in vitro detection step. The prepared magnetic seed dispersions were functionalized using pyrrole and pyrrole-2-carboxylic acid. The obtained core-shell particles were characterized in terms of particle size, size distribution, magnetization properties, FTIR analysis, surface morphology, chemical composition, and finally, the conducting property of those particles were evaluated by cyclic voltammetry. The obtained functional submicron highly magnetic particles are found to be conducting material bearing function carboxylic group on the surface. These promising conducting magnetic particles can be used for both transport and lab-on-a-chip detection. PMID- 26838899 TI - Effect of sintering temperature variations on fabrication of 45S5 bioactive glass ceramics using rice husk as a source for silica. AB - 45S5 bioactive glass is a highly bioactive substance that has the ability to promote stem cell differentiation into osteoblasts--the cells that create bone matrix. The aim of this work is to analyze physical and mechanical properties of 45S5 bioactive glass fabricated by using rice husk ash as its silica source. The 45S5 bioactive glass was prepared by melting the batch at 1300 degrees C for 3h. The samples were sintered at different temperatures ranging from 900 to 1050 degrees C with a fixed dwell-time of 2h. The phase transitions, density, porosity and microhardness values were investigated and reported. DTA analysis was used to examine the crystallization temperatures of the glasses prepared. We found that the sintering temperature had a significant effect on the mechanical and physical properties of the bioactive glass. The XRD showed that when the sintering temperature was above 650 degrees C, crystallization occurred and bioactive glass-ceramics with Na2Ca2Si3O9, Na2Ca4(PO4)2SiO4 and Ca3Si2O7 were formed. The optimum sintering temperature resulting in maximum mechanical values was around 1050 degrees C, with a high density of 2.27 g/cm(3), 16.96% porosity and the vicker microhardness value of 364HV. Additionally, in vitro assay was used to examine biological activities in stimulated body fluid (SBF). After incubation in SBF for 7 days, all of the samples showed formations of apatite layers indicating that the 45S5 bioactive glasses using rice husk as a raw material were also bioactive. PMID- 26838900 TI - Collagen/silk fibroin composite scaffold incorporated with PLGA microsphere for cartilage repair. AB - For cartilage repair, ideal scaffolds should mimic natural extracellular matrix (ECM) exhibiting excellent characteristics, such as biocompatibility, suitable porosity, and good cell affinity. This study aimed to prepare a collagen/silk fibroin composite scaffold incorporated with poly-lactic-co-glycolic acid (PLGA) microsphere that can be applied in repairing cartilage. To obtain optimum conditions for manufacturing a composite scaffold, a scaffold composed of different collagen-to-silk fibroin ratios was evaluated by determining porosity, water absorption, loss rate in hot water, and cell proliferation. Results suggested that the optimal ratio of collagen and silk fibroin composite scaffold was 7:3. The microstructure and morphological characteristics of the obtained scaffold were also examined through scanning electron microscopy and Fourier transform infrared spectroscopy. The results of in vitro fluorescence staining of bone marrow stromal cells revealed that collagen/silk fibroin composite scaffold enhanced cell proliferation without eliciting side effects. The prepared composite scaffold incorporated with PLGA microsphere was implanted in fully thick articular cartilage defects in rabbits. Collagen/silk fibroin composite scaffold with PLGA microspheres could enhance articular cartilage regeneration and integration between the repaired cartilage and the surrounding cartilage. Therefore, this composite will be a promising material for cartilage repair and regeneration. PMID- 26838901 TI - In vivo comparative study of tissue reaction to bare and antimicrobial polymer coated transcutaneous implants. AB - We coated transcutaneous implants made of titanium alloy Ti6Al4V with copolymer dimethyl (2-methacryloyloxy-ethyl) phosphonate and 4-vinylpyridine and investigated the tissue reaction with respect to its biocompatible and antimicrobial properties in vivo. We distinguished between clinically observable superficial inflammations and histologically detectable deep infections. The vinylpyridine moieties were transferred into cationic pyridinium groups by reaction with hexyl bromide. Thus polymers with both antimicrobial capacity and good biocompatibility were obtained. In a short-term study, we implanted specially designed bare or coated implants in hairless but immunocompetent mice and analyzed the tissue reaction histologically. No difference was found between bare and coated implants in the initial healing phase of up to 14 days; however, after 21 days the scar tissue formation was higher in the bare implant group. The degree of epithelial downgrowth was comparable in both groups at any time point. In a long-term study of up to 168 days, we analyzed resistance to infection. In the bare implant group, 7 of the 12 implantation sites became infected deep whereas in the coated implant group only two deep infections were observed. The other implantation sites showed only superficial signs of inflammation. These results generally accord with previous in-vitro studies. PMID- 26838902 TI - Amoxicillin functionalized gold nanoparticles reverts MRSA resistance. AB - In this study, we have described the biosynthesis of biocompatible gold nanoparticles (GNPs) from aqueous extract of the aerial parts of a pteridophyte, "Adiantum philippense" by microwave irradiation and its surface functionalization with broad spectrum beta lactam antibiotic, amoxicillin (Amox). The functionalization of amoxicillin on GNPs (GNP-Amox) was carried out via electrostatic interaction of protonated amino group and thioether moiety mediated attractive forces. The synthesized GNPs and GNP-Amox were physicochemically characterized. UV-Vis spectroscopy, Zeta potential, XRD, FTIR and SERS (surface enhanced raman spectra) results confirmed the loading of Amox into GNPs. Loading of Amox to GNPs reduce amoxicillin cytotoxicity, whereas GNPs were found to be nontoxic to mouse fibroblast cell line (L929) as evident from MTT and acridine orange/ethidium bromide (AO/EtBr) live/dead cell assays. The GNP-Amox conjugates demonstrated enhanced broad-spectrum bactericidal activity against both Gram positive and Gram-negative bacteria. Furthermore, in-vitro and in-vivo assays of GNP-Amox revealed potent anti-MRSA activity and improved the survival rate. This indicates the subversion of antibiotic resistance mechanism by overcoming the effect of high levels of beta-lactamase produced by methicillin resistant Staphylococcus aureus (MRSA). Taken together, this study demonstrates the positive attributes from GNP-Amox conjugates as a promising antibacterial therapeutic agent against MRSA as well as other pathogens. PMID- 26838903 TI - Evaluation of tetraethoxysilane (TEOS) sol-gel coatings, modified with green synthesized zinc oxide nanoparticles for combating microfouling. AB - Green synthesis of zinc oxide nanoparticles (ZnO-NPs) is gaining importance as an eco-friendly alternative to conventional methods due to its enormous applications. The present work reports the synthesis of ZnO-NPs using the endosperm of Cocos nucifera (coconut water) and the bio-molecules responsible for nanoparticle formation have been identified. The synthesized nanoparticles were characterized using UV-Visible spectroscopy (UV-Vis), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Transmission Electron Microscopy (TEM) and Zeta potential measurement. The results obtained reveal that the synthesized nanoparticles are moderately stable with the size ranging from 20 to 80 nm. The bactericidal effect of the nanoparticles was proved by well diffusion assay and determination of minimum inhibitory concentration (MIC) against marine biofilm forming bacteria. Further the green synthesized ZnO-NPs were doped with TEOS sol-gels (TESGs) in order to assess their antimicrofouling capability. Different volumes of liquid sol-gels were coated on to 96-well microtitre plate and cured under various conditions. The optimum curing conditions were found to be temperature 60 degrees C, time 72 h and volume 200 MUl. Antiadhesion test of the undoped (SG) and ZnO-NP doped TEOS sol-gel (ZNSG) coatings were evaluated using marine biofilm forming bacteria. ZNSG coatings exhibited highest biofilm inhibition (89.2%) represented by lowest OD value against Pseudomonasotitidis strain NV1. PMID- 26838905 TI - Pore formation mechanism of porous poly(DL-lactic acid) matrix membrane. AB - Porous PLA structure has been widely used in cell transplantation, drug carrier and wound dressing. The porous structure can be controlled depending on the choice of the polymer, solvent, nonsolvent and preparation parameters. In this study, the porous PLA matrix membranes were prepared by adding PEG 400 in PLA solution using dichloromethane (DCM) as solvent prior to casting. The influence of other liquids as co-solvent on pore formation and the structural change during membrane formation were evaluated. The co-solvents affected both porous topography and mechanical properties of PLA membrane. The porous matrix were produced when the non-solvent of PLA was used as co-solvent. Cryo-SEM micrographs revealed that PEG 400 still remained in the PLA porous matrix membrane. From the tracking of the structural change during film formation, the PLA-PEG solution changed into porous structure by liquid liquid phase separation and solidification processes, respectively. Thermogravimetric analysis revealed that PLA-PEG in DCM solution exhibited the two-step of weight loss, the first step occurred from DCM evaporation and the second step occurred from the degradation of PLA-PEG matrix. The liquid-liquid phase separation and solidification started when the amount of DCM was higher than PEG 400 for 2.67 folds and DCM amount was equal to that of PEG 400, respectively. These results could clarify the pore formation mechanism of porous PLA membrane and will be useful for the further investigation and application. PMID- 26838904 TI - Synthesis of magnesium- and manganese-doped hydroxyapatite structures assisted by the simultaneous incorporation of strontium. AB - Samples of crystalline hydroxyapatite (HA) with and without the addition of individual Mg(2+), Mn(2+) and Sr(2+) ions and samples with the addition of all three ions simultaneously were prepared using the precipitation method in an aqueous medium. Chemical, structural, spectroscopic and thermophysical analyses of the synthesized samples were conducted. The obtained results indicate that Sr(2+) ions were easily incorporated into the HA crystal structure, whereas it was difficult to incorporate Mg(2+) and Mn(2+) ions into the HA lattice when these ions were individually introduced into the samples. The synthesis of HA with Mg(2+) or Mn(2+) ions is characterized by the formation of HA with a low concentration of doping elements that is outweighed by the amount of these atoms present in less biocompatible phases that formed simultaneously. However, the incorporation of Sr(2+) along with Mg(2+) and Mn(2+) ions into the samples allowed for the synthesis of HA with considerably higher concentrations of Mg(2+) and Mn(2+) in the crystal lattice. PMID- 26838906 TI - Double targeting, controlled release and reversible delivery of daunorubicin to cancer cells by polyvalent aptamers-modified gold nanoparticles. AB - Clinical use of daunorubicin (Dau) in treatment of leukemia has been restricted because of its cardiotoxicity. Targeted delivery of anticancer drugs could decrease their off-target effects and enhance their efficacy. In this study a modified polyvalent aptamers (PA)-Daunorubicin (Dau)-Gold nanoparticles (AuNPs) complex was designed and its efficacy was assessed in Molt-4 cells (human acute lymphoblastic leukemia T-cell, target). Dau was efficiently loaded (10.5 MUM) onto 1mL of PA-modified AuNPs. Dau was released from the PA-Dau-AuNPs complex in a pH-sensitive manner (faster release at pH5.5). The results of flow cytometry analysis indicated that the PA-Dau-AuNPs complex was efficiently internalized into target cells, but not into nontarget cells. The results of MTT assay were consistent with the internalization data. PA-Dau-AuNPs complex had less cytotoxicity in U266 cells compared to Dau alone and even Apt-Dau-AuNPs complex. The PA-Dau-AuNPs complex had more cytotoxicity in Molt-4 cells compared to Dau alone and even Apt-Dau-AuNPs complex. Cytotoxicity of PA-Dau-AuNPs complex was effectively antagonized using antisense of polyvalent aptamers. In conclusion, the designed drug delivery system inherited the properties of efficient drug loading, tumor targeting, pH-dependent drug release and controllable delivery of Dau to tumor cells. PMID- 26838907 TI - Fluorescence enhancement of glutaraldehyde functionalized polyaniline nanofibers in the presence of aromatic amino acids. AB - Polyaniline nanofibers (PNFs) synthesized by dilute polymerization method have been surface functionalized with glutaraldehyde at their N-terminals in Phosphate Buffered Saline (PBS) at P(H)=7.4 in order to achieve improved interaction of surface functionalized polyaniline nanofibers (SF-PNFs) with aromatic amino acids Tyrosine, Tryptophan and Phenylalanine through incorporation of aldehyde (-CHO) and hydroxyl (-OH) functionalities. HRTEM reveals nanofibers of average diameter of 35.66 nm. FESEM depicts interconnected networks of nanofibers of polyaniline (PAni). UV-visible absorption and Fluorescence spectroscopy indicate that the PNFs and SF-PNFs are in emeraldine base (EB) form. FT-IR, (1)H NMR spectroscopy suggests covalent interactions of SF-PNFs with aromatic amino acids and possible reaction mechanisms have been proposed based on these results. Remarkable enhancement in fluorescence signals of SF-PNFs in the presence of aromatic amino acids has been observed and the apparent binding constant (KA) and the number of binding sites (n) have been calculated using fluorescence enhancement equation. The KA value is found to be highest for SF-PNFs+Tyrosine and n is two for all the polymer amino acid complexes, which are in agreement with the FT-IR and (1)H NMR results. Fluorescence resonance energy transfer (FRET) efficiency has been found to be highest for SF-PNFs+Tyrosine giving maximum fluorescence enhancement. The study of interaction mechanisms by means of an extremely sensitive technique like fluorescence using SF-PNFs as a substrate may provide a promising analytical tool for detection and monitoring any biochemical reactions involving these three aromatic amino acids. PMID- 26838908 TI - Experimental design of membrane sensor for selective determination of phenazopyridine hydrochloride based on computational calculations. AB - Computational study has been done electronically and geometrically to select the most suitable ionophore to design a novel sensitive and selective electrochemical sensor for phenazopyridine hydrochloride (PAP). This study has revealed that sodium tetraphenylbarate (NaTPB) fits better with PAP than potassium tetrakis (KTClPB). The sensor design is based on the ion pair of PAP with NaTPB using dioctyl phthalate as a plasticizer. Under optimum conditions, the proposed sensor shows the slope of 59.5 mV per concentration decade in the concentration range of 1.0 * 10(-2)-1.0 * 10(-5) M with detection limit 8.5 * 10(-6) M. The sensor exhibits a very good selectivity for PAP with respect to a large number of interfering species as inorganic cations and sugars. The sensor enables track of determining PAP in the presence of its oxidative degradation product 2, 3, 6 Triaminopyridine, which is also its toxic metabolite. The proposed sensor has been successfully applied for the selective determination of PAP in pharmaceutical formulation. Also, the obtained results have been statistically compared to a reported electrochemical method indicating no significant difference between the investigated method and the reported one with respect to accuracy and precision. PMID- 26838909 TI - Mesoporous silica nanoparticles with bilayer coating of poly(acrylic acid-co itaconic acid) and human serum albumin (HSA): A pH-sensitive carrier for gemcitabine delivery. AB - Novel bilayer coated mesoporous silica nanoparticle (MCM-41) based on pH sensitive poly(acrylic acid-co-itaconic acid) and human serum albumin (HSA) was designed for controlled delivery of gemcitabine (anticancer drug) to cancer cells. The shell around the mesoporous silica has bilayer structure. Poly(acrylic acid-co-itaconic acid) was used as pH-sensitive inner shell and human serum albumin, HSA, was used as outer shell. The core-shell structure was formed due to electrostatic interaction between ammonium groups of modified MCM-41 and carboxylate groups of copolymer. Also, the albumin layer was wrapped around the copolymer coated nanoparticle by electrostatic interaction between ammonium groups from protein and carboxylate ions of copolymer shell. Moreover, the maximum release occurred at pH 5.5 (pH of endosomes) because the bilayer shell collapsed at this pH. The drug nanocarrier would be a good candidate for tumor therapy due to its biocompatibility, controlled release and pH responsive behavior. PMID- 26838910 TI - Gene delivery efficiency and cytotoxicity of heterocyclic amine-modified PAMAM and PPI dendrimers. AB - Poly-(amidoamine) (PAMAM) and poly-(propylenimine) (PPI) are the two most widely investigated dendrimers for drug and gene delivery. In order to enhance DNA transfection activity of these dendrimers, generation 3 and 4 PAMAM and generation 4 and 5 PPI were modified by partial substitution of surface primary amines with histidine, pyridine, and piperazine, which have buffering capacity properties. It was shown that higher dendrimer generations and higher grafting percentages (30% and 50% of primary amines) were associated with higher transfection activity. Pyridine was the most effective substituent for PPI, while piperazine-modified PAMAM dendrimers showed the best transfection efficiency among PAMAM-based vectors in murine neuroblastoma (Neuro-2a) cells. None of the modified carriers showed remarkable cytotoxicity in vitro. Pretreatment of cells with bafilomycin A indicated that endosomal buffering capacity is the main mechanism of endosomal escape. In conclusion, PAMAM and PPI may exhibit different gene delivery efficiency and cytotoxicity profiles with the same chemical modifications. These modified dendrimers could be considered as efficient and safe gene carriers in neuroblastoma cells in vitro. PMID- 26838911 TI - Synthesis and characterization of a HAp-based biomarker with controlled drug release for breast cancer. AB - A biocompatible hybrid porous polymer-ceramic material was synthesized to be used as a biomarker in the treatment of breast cancer. This device was equipped with the capacity to release medicaments locally in a controlled manner. The biomaterial was Hydroxyapatite(HAp)-based and had a controlled pore size and pore volume fraction. It was implemented externally using a sharp end and a pair of barbed rings placed opposite each other to prevent relative movement once implanted. The biomarker was impregnated with cis-diamine dichloride platinum (II) [Cl2-Pt-(NH3)2]; the rate of release was obtained using inductively coupled plasma atomic emission spectroscopy (ICP-AES), and release occurred over the course of three months. Different release profiles were obtained as a function of the pore volume fraction. The biomaterial was characterized using scanning electron microscopy (SEM) and Raman spectroscopy. PMID- 26838912 TI - Synthesis, X-ray crystal structures and thermal analyses of some new antimicrobial zinc complexes: New configurations and nano-size structures. AB - Some new five coordinated ZnLX2 complexes, where L is N3-Schiff base ligand obtained by condensation reaction between diethylenetriamine and (E)-3-(2 nitrophenyl)acrylaldehyde and X (Cl(-), Br(-), I(-), N3(-) and NCS(-)), were synthesized and characterized by FT-IR, (1)H and (13)CNMR, UV-visible, ESI-mass spectra and molar conductivity measurements. The structures of zinc iodide and thiocyanate complexes were determined by X-ray crystallographic analysis. The X ray results showed that the Zn (II) center in these complexes is five-coordinated in a distorted trigonal-bipyramidal configuration. Zinc iodide and thiocyanate complexes crystallize in the monoclinic and triclinic systems with space groups of C2/c and P1- with eight and two molecules per unit cell respectively. The crystal packing of the complexes consists of intermolecular interactions such as C-H(...)O and C-H(...)I, C-H(...)S, N(...)O, together with pi-pi stacking and some other unexpected interactions. The mentioned interactions cause three dimensional supramolecular structure in the solid state. Zinc complexes were also prepared in nano-structure by sonochemical method confirmed by XRD, SEM and TEM analyses. Moreover, ZnO nanoparticles were synthesized by direct thermolysis of zinc iodide complex. Furthermore, antimicrobial and thermal properties of the compounds were completely investigated. PMID- 26838913 TI - [PHEMA/PEI]-Cu(II) based immobilized metal affinity chromatography cryogels: Application on the separation of IgG from human plasma. AB - The immobilized metal-affinity chromatography (IMAC) has gained significant interest as a widespread separation and purification tool for therapeutic proteins, nucleic acids and other biological molecules. The enormous potential of IMAC for proteins with natural surface exposed-histidine residues and for recombinant proteins with histidine clusters. Cryogels as monolithic materials have recently been proposed as promising chromatographic adsorbents for the separation of biomolecules in downstream processing. In the present study, IMAC cryogels have been synthesized and utilized for the adsorption and separation of immunoglobulin G (IgG) from IgG solution and whole human plasma. For this purpose, Cu(II)-ions were coupled to poly(hydroxyethyl methacrylate) PHEMA using poly(ethylene imine) (PEI) as the chelating ligand. In this study the cryogels formation optimized by the varied proportion of PEI from 1% to 15% along with different amounts of Cu (II) as chelating metal. The prepared cryogels were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis. The [PHEMA/PEI]-Cu(II) cryogels were assayed for their capability to bind the human IgG from aqueous solutions. The IMAC cryogels were found to have high affinity toward human IgG. The adsorption of human IgG was investigated onto the PHEMA/PEI cryogels with (10% PEI) and the concentration of Cu (II) varied as 10, 50, 100 and 150 mg/L. The separation of human IgG was achieved in one purification step at pH7.4. The maximum adsorption capacity was observed at the [PHEMA/PEI]-Cu(II) (10% PEI) with 72.28 mg/g of human IgG. The purification efficiency and human IgG purity were investigated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE). PMID- 26838915 TI - Modified glassy carbon electrodes based on carbon nanostructures for ultrasensitive electrochemical determination of furazolidone. AB - The electrochemical behavior of Furazolidone (Fu) was investigated on the surface of the glassy carbon electrode modified with different carbon nanomaterials, including carbon nanotubes (CNTs), carbon nanoparticles (CNPs), nanodiamond graphite (NDG), graphene oxide (GO), reduced graphene oxide (RGO) and RGO-CNT hybrids (various ratios) using linear sweep voltammetry (LSV). The results of voltammetric studies exhibited a considerable increase in the cathodic peak current of Fu at the RGO modified GCE, compared to other modified electrodes and also bare GCE. The surface morphology and nature of the RGO film was thoroughly characterized by scanning electron microscopy (SEM), atomic force microscopy (AFM), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) techniques. The modified electrode showed two linear dynamic ranges of 0.001-2.0 MUM and 2.0-10.0 MUM with a detection limit of 0.3 nM for the voltammetric determination of Fu. This sensor was used successfully for Fu determination in pharmaceutical and clinical preparations. PMID- 26838916 TI - Tunable drug delivery using chemoselective functionalization of hydrogels. AB - In the last decades interests on cleavable linkers are growing due to the need to develop controlled drug delivery systems in biochemical and therapeutic applications. The synthesis of hydrogels as devices capable to maintain the drug level within a desired range for a long and sustained period of time is a leading strategy for this aim. However with respect to the good results obtained with antibodies and peptides there are a lot of problems related to the quick and uncontrolled diffusion of small molecules through hydrogel pores. In this work, we propose the functionalization of polyethylene glycol (PEG) chains with two different pH-sensitive linkers, ester and hydrazone, and their application as building blocks of microwave-assisted hydrogels for controlled delivery of small hydrophilic drugs. As drug mimetic we used Rhodamine B, a harmless fluorophore with steric hindrance and reactive groups similar to many small hydrophilic drugs. At physiological and low basic conditions, the cleavability of ester and hydrazone spacer evidenced the possibility to delay the release of drugs from the scaffold compared to hydrogels where drug was entrapped within the network only due to its steric hindrance. The obtained release profiles were compared, underlining the opportunity to tune the release rate using the synthesized hydrogels. PMID- 26838914 TI - Layer-by-layer films containing peptides of the Cry1Ab16 toxin from Bacillus thuringiensis for potential biotechnological applications. AB - Cry1Ab16 is a toxin of crystalline insecticidal proteins that has been widely used in genetically modified organisms (GMOs) to gain resistance to pests. For the first time, in this study, peptides derived from the immunogenic Cry1Ab16 toxin (from Bacillus thuringiensis) were immobilized as layer-by-layer (LbL) films. Given the concern about food and environmental safety, a peptide with immunogenic potential, PcL342-354C, was selected for characterization of the electrochemical, optical, and morphological properties. The results obtained by cyclic voltammetry (CV) showed that the peptide have an irreversible oxidation process in electrolyte of 0.1 mol . L(-1) potassium phosphate buffer (PBS) at pH7.2. It was also observed that the electrochemical response of the peptide is governed mainly by charge transfer. In an attempt to maximize the electrochemical signal of peptide, it was intercalated with natural (agar, alginate and chitosan) or synthetic polymers (polyethylenimine (PEI) and poly(sodium 4-styrenesulfonate (PSS)). The presence of synthetic polymers on the film increased the electrochemical signal of PcL342-354C up to 100 times. Images by Atomic Force Microscopy (AFM) showed that the immobilized PcL342-354C formed self-assembled nanofibers with diameters ranging from 100 to 200 nm on the polymeric film. By UV Visible spectroscopy (UV-Vis) it was observed that the ITO/PEI/PSS/PcL342-354C film grows linearly up to the fifth layer, thereafter tending to saturation. X ray diffraction confirmed the presence on the films of crystalline ITO and amorphous polypeptide phases. In general, the ITO/PEI/PSS/PcL342-354C film characterization proved that this system is an excellent candidate for applications in electrochemical sensors and other biotechnological applications for GMOs and environmental indicators. PMID- 26838917 TI - Differential pulse voltammetric determination of nanomolar concentrations of antiviral drug acyclovir at polymer film modified glassy carbon electrode. AB - An electrochemical sensor for the sensitive detection of acyclovir was developed by the electropolymerization of Eriochrome black T at a pretreated glassy carbon electrode. The surface morphology of the modified electrode was characterized by field emission scanning electron microscopy. Under the optimized conditions, a significant electrochemical improvement was observed toward the electrooxidation of acyclovir on the modified electrode surface relative to the unmodified electrode. The detection limit of 12 nM and two linear calibration ranges of 0.03 0.3 MUM and 0.3-1.5 MUM were obtained for acyclovir determination using a differential pulse voltammetric method in acetate buffer (0.1 M, pH 4.0). Real sample studies were carried out in human blood serum and pharmaceutical formulations, which offered good recovery (98-102%). The electrode showed excellent reproducibility, selectivity and antifouling effects. PMID- 26838918 TI - In vitro and in vivo comparison of binary Mg alloys and pure Mg. AB - Biodegradable materials are under investigation due to their promising properties for biomedical applications as implant material. In the present study, two binary magnesium (Mg) alloys (Mg2Ag and Mg10Gd) and pure Mg (99.99%) were used in order to compare the degradation performance of the materials in in vitro to in vivo conditions. In vitro analysis of cell distribution and viability was performed on discs of pure Mg, Mg2Ag and Mg10Gd. The results verified viable pre-osteoblast cells on all three alloys and no obvious toxic effect within the first two weeks. The degradation rates in in vitro and in vivo conditions (Sprague-Dawley(r) rats) showed that the degradation rates differ especially in the 1st week of the experiments. While in vitro Mg2Ag displayed the fastest degradation rate, in vivo, Mg10Gd revealed the highest degradation rate. After four weeks of in vitro immersion tests, the degradation rate of Mg2Ag was significantly reduced and approached the values of pure Mg and Mg10Gd. Interestingly, after 4 weeks the estimated in vitro degradation rates approximate in vivo values. Our systematic experiment indicates that a correlation between in vitro and in vivo observations still has some limitations that have to be considered in order to perform representative in vitro experiments that display the in vivo situation. PMID- 26838919 TI - Carbonated hydrocalumite synthesized by the microwave method as a possible antacid. AB - A carbonated hydrocalumite was synthesized by the microwave method for being used as antacid. The gel was formed using Ca and Al nitrate solutions in a basic medium (NaOH+Na2CO3), then, this gel was aged and heated in a domestic microwave for 2.5 min (1250 W). The obtained white solid was washed with distilled water, dried in an oven at 100 degrees C for 18 h and characterized by different techniques such as: X-ray diffraction (XRD), Fourier transformed infrared spectroscopy (FT-IR), BET surface area measurements, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX). Finally, the carbonated hydrocalumite was tested as antacid by using a synthetic gastric juice and its activity was compared with a commercial antacid formulated with hydrotalcite. Results showed that the carbonated hydrocalumite was more effective than that commercial antacid. PMID- 26838920 TI - Preparation and properties of EDC/NHS mediated crosslinking poly (gamma-glutamic acid)/epsilon-polylysine hydrogels. AB - In this paper, a novel pH-sensitive poly (amino acid) hydrogel based on poly gamma-glutamic acid (gamma-PGA) and epsilon-polylysine (epsilon-PL) was prepared by carbodiimide (EDC) and N-hydroxysuccinimide (NHS) mediated polymerization. The influence of PGA/PL molar ratio and EDC/NHS concentration on the structure and properties was studied. Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) proved that hydrogels were crosslinked through amide bond linkage, and the conversion rate of a carboxyl group could reach 96%. Scanning electron microscopy (SEM) results showed a regularly porous structure with 20 MUm pore size in average. The gelation time in the crosslink process of PGA/PL hydrogels was within less than 5 min. PGA/PL hydrogels had excellent optical performance that was evaluated by a novel optotype method. Furthermore, PGA/PL hydrogels were found to be pH-sensitive, which could be adjusted to the pH of swelling media intelligently. The terminal pH of swelling medium could be controlled at 5 +/- 1 after equilibrium when the initial pH was within 3-11. The swelling kinetics was found to follow a Voigt model in deionized water but a pseudo-second-order model in normal saline and phosphate buffer solution, respectively. The differential swelling degrees were attributed to the swelling theory based on the different ratio of -COOH/-NH2 and pore size in hydrogels. The results of mechanical property indicated that PGA/PL hydrogels were soft and elastic. Moreover, PGA/PL hydrogels exhibited excellent biocompatibility by cell proliferation experiment. PGA/PL hydrogels could be degraded in PBS solution and the degradation rate was decreased with the increase of the molar ratio of PL. Considering the simple preparation process and pH-sensitive property, these PGA/PL hydrogels might have high potential for use in medical and clinical fields. PMID- 26838921 TI - Development of meniscus substitutes using a mixture of biocompatible polymers and extra cellular matrix components by electrospinning. AB - Despite the significant advances in the meniscus tissue engineering field, it is difficult to recreate the complex structure and organization of the collagenous matrix of the meniscus. In this work, we developed a meniscus prototype to be used as substitute or scaffold for the regeneration of the meniscal matrix, recreating the differential morphology of the meniscus by electrospinning. Synthetic biocompatible polymers were combined with the extracellular matrix component, collagen and used to replicate the meniscus. We studied the correlation between mechanical and structural properties of the polymer blend as a function of collagen concentration. Fibers were collected on a surface of a rapidly rotating precast mold, to accurately replicate each sectional morphology of the meniscus; different electro-tissues were produced. Detailed XRD analyses exhibited structural changes developed by electrospinning. We achieved to integrate all these electro-tissues to form a complete synthetic meniscus. Vascularization tests were performed to assess the potential use of our novel polymeric blend for promising meniscus regeneration. PMID- 26838922 TI - The influence of topography on tissue engineering perspective. AB - The actual in vivo tissue scaffold offers a three-dimensional (3D) structural support along with a nano-textured surfaces consist of a fibrous network in order to deliver cell adhesion and signaling. A scaffold is required, until the tissue is entirely regenerated or restored, to act as a temporary ingrowth template for cell proliferation and extracellular matrix (ECM) deposition. This review depicts some of the most significant three dimensional structure materials used as scaffolds in various tissue engineering application fields currently being employed to mimic in vivo features. Accordingly, some of the researchers' attempts have envisioned utilizing graphene for the fabrication of porous and flexible 3D scaffolds. The main focus of this paper is to evaluate the topographical and topological optimization of scaffolds for tissue engineering applications in order to improve scaffolds' mechanical performances. PMID- 26838923 TI - Role of pore size and morphology in musculo-skeletal tissue regeneration. AB - Biomaterials in the form of scaffolds hold great promise in the regeneration of diseased tissues. The scaffolds stimulate cellular adhesion, proliferation and differentiation. While the scaffold composition will dictate their biocompatibility, their porosity plays a key role in allowing proper cell penetration, nutrient diffusion as well as bone ingrowth. Porous scaffolds are processed with the help of a wide variety of techniques. Designing scaffolds with the appropriate porosity is a complex issue since this may jeopardize other physico-chemical properties. From a macroscopic point of view, parameters such as the overall architecture, pore morphology, interconnectivity and pore size distribution, have unique roles in allowing bone ingrowth to take place. From a microscopic perspective, the adsorption and retention of proteins in the microporosities of the material will dictate the subsequent cell adhesion. Therefore, the microstructure of the substrate can determine cell proliferation as well as the expression of specific osteogenic genes. This review aims at discussing the effect of micro- and macroporosity on the physico-chemical and biological properties of scaffolds for musculo-skeletal tissue regeneration. PMID- 26838924 TI - Processing and characterization of silk sericin from Bombyx mori and its application in biomaterials and biomedicines. AB - Bombyx mori silk is composed of 60-80% fibroin, 15-35% sericin and 1-5% non sericin component including wax, pigments, sugars and other impurities. For two decades, the protein-based silk fibroin was extensively used in the research and development of medical biomaterials and biomedicines. Sericin is frequently ignored and abandoned as a byproduct or waste in the processing of traditional silk fabrics, silk floss or modern silk biomaterials. However, similar to fibroin, sericin is not only a highly useful biological material, but also a lot of biological activity. Moreover, the non-sericin component present with sericin in the cocoon shell also has a strong biological activity. In this review, the extraction and recovery methods of sericin and the non-sericin component from the cocoon layer are reported, and their composition, properties and biological activity are described to produce a comprehensive report on biomedical materials and biological drugs. In addition, related problems or concerns present in the research and development of sericin are discussed, and a potential application of sericin in sustainable development is also presented. PMID- 26838925 TI - Biomedical applications of the graphene-based materials. AB - Graphene, a rapidly rising star, has gained extensive research interests lately due to its excellent properties--such as the exceptional optical, electrical, thermal and mechanical features--which are superior to other materials, so it is called "two-dimensional magical materials". This article presents diverse types and various properties of graphene-based materials, and the current methods for the surface modifications of the graphene-based materials are briefly described. In addition, the in vivo and in vitro cytotoxicity of graphene-based materials are comprehensively discussed. What's more, a summary of its biomedical applications such as drug/gene delivery, photothermal therapy, photodynamic therapy and multimodality therapy is also offered. Finally, an outlook of the graphene-based materials and the challenges in this field are briefly discussed. PMID- 26838926 TI - Antibacterial titanium surfaces for medical implants. AB - Bacterial contamination is a critical problem in different fields (ranging from everyday life to space missions, and from medicine to biosensing). Specifically, in the case of medical implants, foreign materials are preferential sites for bacterial adhesion and microbial contamination, which can lead to the development of prosthetic infections. These problems can in turn lead to the necessity of a prolonged antibiotic therapy (which can last for years) and eventually to the removal of the device, with a consequent significant increase in the hospitalization times and costs, together with a stressful, painful and critical situation for the patient. Commercially pure titanium and its alloys are the most commonly used materials for permanent implants in contact with bone, and the prevention of infections on their surface is therefore a crucial challenge for orthopaedic and dental surgeons. The problem of the bacterial contamination of medical implants is briefly described in the first part of the present review. Then the most important inorganic antibacterial agents (Ag, Cu and Zn) are described, and this is followed by a review of the reported attempts of their introduction onto the surface of Ti-based substrates. PMID- 26838927 TI - Electrochemical and photoelectrochemical nano-immunesensing using origami paper based method. AB - Patterned paper has characteristics that lead to miniaturized assays that run by capillary action with small volumes of fluids. These methods suggest a path for the development of simple, inexpensive, and portable diagnostic assays that can be useful in remote settings, where simple immunoassays are becoming increasingly important for detecting disease and monitoring health. Incorporation of nanomaterials plays a major role in sensing probe immobilization and detection sensitivity of paper-based devices. Nanomaterial properties, such as increased surface area, have aided with signal amplification and lower detection limits. This review focuses on application of nanomaterials as signal amplification elements on origami paper-based electro-analytical devices for immune biomarkers detection with a brief introduction about various fabrication techniques and designs, biological and detection methods. In this review, we comprehensively summarize the selected latest research articles from 2013 to May 2015 on application of nanomaterials in various types of origami paper based electrochemical and photoelectrochemical immunosensors. The review breaks into two parts. The first part devotes to the development and applications of nanomaterials in electrochemical immunesensing. The second part provides an overview of recent origami paper based photoelectrochemical immunosensors. PMID- 26838928 TI - Pharmacogenomic study using bio- and nanobioelectrochemistry: Drug-DNA interaction. AB - Small molecules that bind genomic DNA have proven that they can be effective anticancer, antibiotic and antiviral therapeutic agents that affect the well being of millions of people worldwide. Drug-DNA interaction affects DNA replication and division; causes strand breaks, and mutations. Therefore, the investigation of drug-DNA interaction is needed to understand the mechanism of drug action as well as in designing DNA-targeted drugs. On the other hand, the interaction between DNA and drugs can cause chemical and conformational modifications and, thus, variation of the electrochemical properties of nucleobases. For this purpose, electrochemical methods/biosensors can be used toward detection of drug-DNA interactions. The present paper reviews the drug-DNA interactions, their types and applications of electrochemical techniques used to study interactions between DNA and drugs or small ligand molecules that are potentially of pharmaceutical interest. The results are used to determine drug binding sites and sequence preference, as well as conformational changes due to drug-DNA interactions. Also, the intention of this review is to give an overview of the present state of the drug-DNA interaction cognition. The applications of electrochemical techniques for investigation of drug-DNA interaction were reviewed and we have discussed the type of qualitative or quantitative information that can be obtained from the use of each technique. PMID- 26838929 TI - Dental materials for cleft palate repair. AB - Numerous bone and soft tissue grafting techniques are followed to repair cleft of lip and palate (CLP) defects. In addition to the gold standard surgical interventions involving the use of autogenous grafts, various allogenic and xenogenic graft materials are available for bone regeneration. In an attempt to discover minimally invasive and cost effective treatments for cleft repair, an exceptional growth in synthetic biomedical graft materials have occurred. This study gives an overview of the use of dental materials to repair cleft of lip and palate (CLP). The eligibility criteria for this review were case studies, clinical trials and retrospective studies on the use of various types of dental materials in surgical repair of cleft palate defects. Any data available on the surgical interventions to repair alveolar or palatal cleft, with natural or synthetic graft materials was included in this review. Those datasets with long term clinical follow-up results were referred to as particularly relevant. The results provide encouraging evidence in favor of dental and other related biomedical materials to fill the gaps in clefts of lip and palate. The review presents the various bones and soft tissue replacement strategies currently used, tested or explored for the repair of cleft defects. There was little available data on the use of synthetic materials in cleft repair which was a limitation of this study. In conclusion although clinical trials on the use of synthetic materials are currently underway the uses of autologous implants are the preferred treatment methods to date. PMID- 26838930 TI - A Lesion on the Ear Resulting From Infection Acquired in the Tropics. PMID- 26838931 TI - Inguinal hernia repair in children: Surgical technique. PMID- 26838932 TI - Presynaptic partner selection during retinal circuit reassembly varies with timing of neuronal regeneration in vivo. AB - Whether neurons can restore their original connectivity patterns during circuit repair is unclear. Taking advantage of the regenerative capacity of zebrafish retina, we show here the remarkable specificity by which surviving neurons reassemble their connectivity upon regeneration of their major input. H3 horizontal cells (HCs) normally avoid red and green cones, and prefer ultraviolet over blue cones. Upon ablation of the major (ultraviolet) input, H3 HCs do not immediately increase connectivity with other cone types. Instead, H3 dendrites retract and re-extend to contact new ultraviolet cones. But, if regeneration is delayed or absent, blue-cone synaptogenesis increases and ectopic synapses are made with red and green cones. Thus, cues directing synapse specificity can be maintained following input loss, but only within a limited time period. Further, we postulate that signals from the major input that shape the H3 HC's wiring pattern during development persist to restrict miswiring after damage. PMID- 26838933 TI - Physical Activity Level and Symptom Duration Are Not Associated After Concussion. AB - BACKGROUND: Physical rest after a concussion has been described as a key component in the management of the injury. Evidence supporting this recommendation, however, is limited. PURPOSE: To examine the association between physical activity and symptom duration in a cohort of patients after a concussion. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: This study included 364 patients who were diagnosed with a concussion, were seen by a physician within 3 weeks of injury, and completed a questionnaire at the initial clinic visit. The questionnaire assessed the postconcussion symptom scale (PCSS) score, previous number of concussions, presence of the loss of consciousness or amnesia at the time of injury, and prior treatment for headaches. During each follow-up clinic visit, physical activity level was self-reported. A Cox proportional hazard model was constructed to determine the association between symptom duration, initial clinic visit responses, and self-reported physical activity level after the injury. RESULTS: Study participants ranged in age from 8 to 27 years (mean age, 15.0 years) and had sustained a mean of 0.8 prior concussions; 222 patients (61%) were male. On initial examination, the mean PCSS score was 34.7. The mean symptom duration was 48.9 days after the injury. Among the variables included in the model, initial PCSS score and female sex were independently associated with symptom duration, while physical activity level after the injury was not. For participants aged between 13 and 18 years, however, higher levels of physical activity after the injury were associated with a shorter symptom duration. CONCLUSION: Results from this study indicate that physical activity after the injury may not be universally detrimental to the recovery of concussion symptoms. PMID- 26838934 TI - Prospective Randomized Study of Objective and Subjective Clinical Results Between Double-Bundle and Single-Bundle Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND: There is controversy as to whether double-bundle anterior cruciate ligament (ACL) reconstruction with hamstring tendon graft (DB-HT) or single bundle ACL reconstruction with patellar tendon graft (SB-PT) obtains the best clinical outcomes. PURPOSE: To compare the short-term clinical outcomes of DB-HT with those of rectangular-tunnel SB-PT (RTSB-PT) at 2-year follow-up and to identify the factors that affect subjective knee functional score. STUDY DESIGN: Randomized controlled trial. Level of evidence, 1. METHODS: Sixty-three male patients (mean age, 26.1 years) and 87 female patients (mean age, 25.8 years) were included in this study and were randomly distributed to either the DB-HT (n = 76) or RTSB-PT (n = 74) group. Clinical outcomes (knee flexion range of motion [ROM], heel-height difference, side-to-side difference in anterior laxity, rotational laxity, and Tegner activity score) were compared between the DB-HT and RTSB-PT groups, and examination of factors affecting subjective outcomes (Knee Injury and Osteoarthritis and Outcome Score [KOOS] results) was performed by multiple linear regression analysis. RESULTS: Fourteen patients (9 DB-HT, 5 RTSB PT) had secondary ACL injury within 2 years after primary ACL reconstruction and were excluded from analysis. In the examination of 136 patients at the 24-month follow-up, there was no significant difference between the 2 groups in clinical or subjective outcomes. The normalized knee extensor strength of the RTSB-PT group showed negative surgical technique effect in the early postoperative phase (P = .005), but there was no significant difference between the 2 groups at the 24-month follow-up (P = .114). There was no significant difference in change of normalized knee flexor strength between the 2 groups (P = .493). Age, sex, body mass index (BMI), and presence of meniscus injury were the factors that affected KOOS subscale scores. CONCLUSION: In this prospective randomized controlled study, there was no significant difference in the incidence of secondary ACL injury and no difference in objective or subjective outcomes between the DB-HT and RTSB-PT reconstruction at 24-month follow-up. Age, sex, presence of meniscus injury, and BMI affected subjective KOOS subscale scores, while surgical technique did not. PMID- 26838935 TI - Acetabular Labral Reconstruction With Autologous Tendon Tissue in a Porcine Model: In Vivo Histological Assessment and Gene Expression Analysis of the Healing Tissue. AB - BACKGROUND: Acetabular labral reconstruction with autologous tendons is the preferred method for treating a severely damaged labrum. However, the healing process of implants remains unknown. Similar to the human acetabular labrum, the porcine acetabular labrum is a fibrocartilage-like tissue. PURPOSE: This study aimed to characterize the histological healing process and gene expression profile of implants in a porcine model of acetabular labral reconstruction. STUDY DESIGN: Descriptive laboratory study. METHODS: Eighteen pigs were included in this study. The pigs underwent unilateral acetabular labral reconstruction. A 1.0 cm-long defect was made at the site of the anterior (cranial) dorsal labrum, which was repaired using an autologous mesogluteus tendon. The pigs were sacrificed at 12 and 24 weeks postoperatively. The implants were subjected to histological assessment and gene expression analysis. The cell phenotype of the implants was visualized using paraffin-embedded sections. RESULTS: Macroscopic observations revealed that at 12 weeks, 8 of 9 implants partially filled the labral defect; by contrast, at 24 weeks, 6 of 9 implants fully filled and 3 implants partially filled the labral defects. Oval- or round-shaped fibrochondrocytes were found in the implants at 12 and 24 weeks. The matrix staining results showed that proteoglycan and collagen types 1 and 2 were more evident in the implants at 24 weeks than at 12 weeks. Gene expression analysis results revealed that COL2A1 and COL3A1 were expressed by the implants to a higher extent at 24 weeks than at 12 weeks; COL2A1 and COL3A1 were also expressed to a higher extent in the implants than in the native tendon. CONCLUSION: On the basis of the results of histological assessment and gene expression analysis, autologous tendon tissue for acetabular labral reconstruction can fully or partially fill labral defects and converts to fibrocartilage, which is rich in proteoglycan and collagen types 1 and 2, at 24 weeks in a porcine model. CLINICAL RELEVANCE: Autologous tendon tissue can be considered as a viable option for acetabular labral reconstruction. PMID- 26838936 TI - Antiepileptic medications and the risk for sudden cardiac death caused by an acute coronary event: a prospective case-control study. AB - BACKGROUND: Epilepsy is associated with sudden death, but the reasons for this association are not well known. Objective We studied the role of antiepileptic drugs (AEDs) as a factor contributing to sudden cardiac death (SCD) in The Finnish Study of the Genotype and Phenotype Characteristics of Sudden Cardiac Death (FinGesture). METHODS AND RESULTS: The FinGesture study compares the characteristics of victims of SCD caused by an autopsy-verified acute coronary event (cases) vs. survivors of an acute coronary event (ACS) (controls). The study population comprised 3737 cases (mean age 64 +/- 12 y) and 3081 controls (mean age 66 +/- 12 y). The use of AED was obtained from death certificates, autopsy/hospital records, national drug imbursement register, and interviews with the relatives. AEDs were more commonly used by the victims of SCD vs. controls (5.5% vs. 2.2%, adjusted odds ratio 2.7, 95% CI; 1.9-3.9; p < 0001). The use of AED for non-epilepsy indications was also more common in the cases than in controls (1.5% vs. 1.0%, p = 0.005). CONCLUSION: A higher rate of AED was observed in victims of SCD than in a control group of ACS patients. Concomitant use of AED could be responsible for a small fraction of deaths due to acute coronary events. Key message Epilepsy has been associated with sudden cardiac death. The use of antiepileptic drugs seems to be associated with an increased risk of sudden cardiac death during a coronary event. Physicians should be aware of the risk related to antiepileptic drugs especially when used for other reasons than epilepsy. PMID- 26838939 TI - An overview of previous studies reporting multiple gigantic odontomas of both jaws. PMID- 26838938 TI - Prolonged but not short-duration blast waves elicit acute inflammation in a rodent model of primary blast limb trauma. AB - BACKGROUND: Blast injuries from conventional and improvised explosive devices account for 75% of injuries from current conflicts; over 70% of injuries involve the limbs. Variable duration and magnitude of blast wave loading occurs in real life explosions and is hypothesised to cause different injuries. While a number of in vivo models report the inflammatory response to blast injuries, the extent of this response has not been investigated with respect to the duration of the primary blast wave. The relevance is that explosions in open air are of short duration compared to those in confined spaces. METHODS: Hindlimbs of adult Sprauge-Dawley rats were subjected to focal isolated primary blast waves of varying overpressure (1.8-3.65kPa) and duration (3.0-11.5ms), utilising a shock tube and purpose-built experimental rig. Rats were monitored during and after the blast. At 6 and 24h after exposure, blood, lungs, liver and muscle tissues were collected and prepared for histology and flow cytometry. RESULTS: At 6h, increases in circulating neutrophils and CD43Lo/His48Hi monocytes were observed in rats subjected to longer-duration blast waves. This was accompanied by increases in circulating pro-inflammatory chemo/cytokines KC and IL-6. No changes were observed with shorter-duration blast waves irrespective of overpressure. In all cases, no histological damage was observed in muscle, lung or liver. By 24h post-blast, all inflammatory parameters had normalised. CONCLUSIONS: We report the development of a rodent model of primary blast limb trauma that is the first to highlight an important role played by blast wave duration and magnitude in initiating acute inflammatory response following limb injury in the absence of limb fracture or penetrating trauma. The combined biological and mechanical method developed can be used to further understand the complex effects of blast waves in a range of different tissues and organs in vivo. PMID- 26838937 TI - Effect of direct and indirect transfer status on trauma mortality in sub Saharan Africa. AB - INTRODUCTION: Traumatic injuries account for the greatest portion of global surgical burden particularly in low- and middle-income countries (LMICs). To assess effectiveness of a developing trauma system, we hypothesize that there are survival differences between direct and indirect transfer of trauma patients to a tertiary hospital in sub Saharan Africa. METHODS: Retrospective analysis of 51,361 trauma patients within the Kamuzu Central Hospital (KCH) trauma registry from 2008 to 2012 was performed. Analysis of patient characteristics and logistic regression modelling for in-hospital mortality was performed. The primary study outcome is in hospital mortality in the direct and indirect transfer groups. RESULTS: There were 50,059 trauma patients were included in this study. 6578 patients transferred from referring facilities and 43,481 patients transported from the scene. The indirect and direct transfer cohorts were similar in age and sex. The mechanism of injury for transferred patients was 78.1% blunt, 14.5% penetrating, and 7.4% other, whereas for the scene group it was 70.7% blunt, 24.0% penetrating, and 5.2% other. Median times to presentation were 13 (4-30) and 3 (1-14)h for transferred and scene patients, respectively. Mortality rate was 4.2% and 1.6% for indirect and direct transfer cohorts, respectively. A total of 8816 patients were admitted of which 3636 and 5963 were in the transfer and scene cohort, respectively. After logistic regression analysis, the adjusted in hospital mortality odds ratio was 2.09 (1.24-3.54); P=0.006 for indirect transfer versus direct transfer cohort, after controlling for significant covariates. CONCLUSIONS: Direct transfer of trauma patients from the scene to the tertiary care centre is associated with a survival benefit. Our findings suggest that trauma education and efforts directed at regionalization of trauma care, strengthening pre-hospital care and timely transfer from district hospitals could mitigate trauma-related mortality in a resource-poor setting. PMID- 26838940 TI - Folding-induced exciton coupling in homo- and heterodimers of merocyanine dyes. AB - Two identical or different merocyanine dyes were tethered by a rigid diphenylacetylene spacer unit that enables the folding of the two dyes into co facially pi-stacked structures in solvents of low polarity. Whilst the solvent dependent absorption spectra of homodimers of identical dyes are easily interpreted as H-aggregates by exciton theory, the spectra of the heterodimers constitute a novel and more interesting case. PMID- 26838941 TI - 5-Azacytidine partially restores CD20 expression in follicular lymphoma that lost CD20 expression after rituximab treatment: a case report. AB - BACKGROUND: The loss of CD20 protein expression after a rituximab-containing regimen is one of the resistance mechanisms in non-Hodgkin's lymphoma. Recently, it was reported that 5-azacitidine administration upregulates the expression of CD20 in CD20-negative B-cell acute lymphoblastic leukemia. Here we report a similar upregulation in a patient with follicular lymphoma who was treated with 5 azacitidine against secondary myelodysplastic syndrome. CASE PRESENTATION: A 69 year-old Japanese woman with follicular lymphoma with treatment-related myelodysplastic syndrome was negative for the CD20 antibody at the time of her relapse. After treatment of 5-azacytidine for her myelodysplastic syndrome, CD20 expression was upregulated in the follicular lymphoma cells in her peripheral blood. We also observed follicular lymphoma cell stimulation in her peripheral blood due to 5-azacytidine. CONCLUSIONS: Although partial, CD20 expression was upregulated after treatment with 5-azacitidine. However, CD20 expression was not re-upregulated after a second administration of 5-azacitidine and we also observed the risk of lymphoma cell stimulation due to 5-azacitidine. PMID- 26838942 TI - Characterization of carbapenem resistance mechanisms and integrons in Pseudomonas aeruginosa strains from blood samples in a French hospital. AB - Metallo-beta-lactamases (MBLs), porin OprD, integrons, virulence factors and the clonal relationships were characterized in imipenem-resistant Pseudomonas aeruginosa (IRPA) isolates. Fifty-six IRPA strains were recovered from blood samples of different patients at a Toulouse teaching hospital from 2011 to 2013. Susceptibility testing of 14 antibiotics was performed by the disc diffusion method. Detection and characterization of MBLs, the oprD gene and integrons were studied by PCR and sequencing. Thirteen genes involved in the virulence of P. aeruginosa were analysed. Molecular typing of IRPA strains was performed by PFGE and multilocus sequence typing. In this study, 61 % of the IRPA isolates showed a multi-resistance phenotype. The MBL phenotype, detected in three isolates (5.4 %), was linked to the blaVIM-2 gene. The oprD gene was amplified in 55 (98.2 %) IRPA strains, and variations were observed in 54 of them. Insertion sequences (IS) truncating oprD were detected in eight IRPA strains, with the novel ISPa56 identified in two strains. Class 1 integrons were detected in 24 (42.9 %) IRPA strains. The blaVIM-2 gene was found inside the class 1 integron arrangements. The new integrons In1054 (intI1-aacA56-qacEDelta1-sul1) and In1160 (intI1-aacA4 aacC1d-ISKpn4-gcuE-qacEDelta1-sul1) have been described for the first time, to the best of our knowledge, in this study. A high clonal diversity was found in our strains. Among the variety of sequence types (STs) found, ST175, ST233, ST235, ST244 and ST654 were noteworthy as epidemic clones. In conclusion, 5.4 % of IRPA strains showed an MBL phenotype linked to the blaVIM-2 gene. The identified oprD high polymorphism could be implicated in the variable resistance to carbapenems in IRPA strains. The dissemination of high-risk clones is a cause of concern. PMID- 26838943 TI - Lymphatic mapping and sentinel node biopsy in a patient with upper limb Merkel Cell Carcinoma: a case report and brief review of literature. AB - Sentinel node mapping is an integral part of regional lymph node staging in many solid tumors and plays an important role in surgical oncology. This technique has been used with excellent results for non-melanoma skin cancers including Merkel Cell Carcinoma (MCC). In the current study, we reported our first MCC patient who underwent successful sentinel node mapping. We also reviewed the available literature regarding the prognostic significance of sentinel node mapping in cN0 MCC patients. PMID- 26838944 TI - Parathyroid cancer - difficult diagnosis - a case report. AB - Parathyroid cancer is a rare disorder of unclear etiology that is difficult to diagnose and treat. It is most often diagnosed incidentally based on multi-organ non-specific symptoms of hypercalcemia as a consequence of parathyroid hormone oversecretion. We present a case of a male with primary hyperparathyroidism who was diagnosed with parathyroid cancer ectopically located in the mediastinum only after the third surgery. However, due to chronic hypercalcemia, problems with localization and a bad clinical condition, the patient was not able to undergo a radical resection and one year after the first pathological fracture died. Taking into consideration the whole clinical picture we want to emphasize the need to apply comprehensive differential diagnosis of hypercalcemia and localization diagnosis of parathyroid tissue with a use of MIBI scintigraphy accompanied by the computed tomography and magnetic resonance imaging, as the most specific diagnostic tools employed in this pathology. PMID- 26838945 TI - Veteran player tips the scale - V/Q SPECT-CT proves decisive in blunt chest trauma. Case report and brief literature review. AB - A 29-year-old patient after blunt chest trauma with right lung atelectasis and pulmonary empyema was referred for lung ventilation and perfusion scintigraphy before right-sided pneumonectomy. Radionuclide imaging revealed severely reduced perfusion and lack of ventilation in the collapsed right lung. Additionally, it showed a matching lobar perfusion-ventilation defect in the lower left lobe, which, apart from consolidation area in posterior basal segment, appeared normal in computed tomography. A normal perfusion and ventilation pattern was observed in the upper left lobe. Since it was found to be the only functioning lobe, pneumonectomy was excluded from possible treatment options. PMID- 26838946 TI - Problems of diagnostic assessment in advanced pancreatic neuroendocrine neoplasm and treatment implications: a case report and literature review. AB - We are reporting a case of a 55-year-old woman who was diagnosed as having a non functioning pancreatic neuroendocrine neoplasm (NF-PNEN), the World Health Organization (WHO) low grade (G1) with liver metastases. In the staging process the positron emission tomography - computed tomography with Fluorine-18 Fluorodeoxyglucose (F-FDG PET-CT) and spiral CT then the gallium-DOTA-octreotate positron emission tomography - computer tomography (68Ga-DOTATATE PET-CT) shown difference in burden of disease. In first line therapy, everolimus (Afinitor(r), Novartis Pharma GmbH, Germany) at the oral dose of 10 mg once daily and octreotide long-acting release (Sandostatin LAR(r)) 30 mg i.m. every 4 weeks were administered. Then, due to disease progression - radioisotope therapy with b emitter Yttrium-90 (90Y). Based on this experience and on the review of the literature, we recommend that the discrepancy between the imaging studies could be due to heterogeneity of proliferation rate and somatostatin receptors (SSTR) expression within a primary PNEN and metastases. Therefore in such cases of advanced PNEN WHO G1 in the lack of response to everolimus and octreotide LAR administration isotope therapy without a prior chemotherapy should be considered as a palliative treatment according to ESMO Clinical Practice Guidelines and Polish Network of Neuroendocrine Tumors. PMID- 26838947 TI - Computer program for analysis of parathyroid scintigraphy examinations: combination of dual-tracer (subtraction) and double phase single-tracer washout techniques. AB - There is no controversy in the published literature that sensitivity and specificity of parathyroid scintigraphy is superior to other imaging techniques. However no uniform protocol has been established for scintigraphy. In order to analyze parathyroid scintigraphic images in the Department of Nuclear Medicine at the Medical University of Warsaw we have developed a program that allows qualitative and quantitative evaluation of recorded images and motion artifacts correction. This program offers a uniform procedure of analysis of parathyroid imaging results in diagnostic centers, accelerates the analysis of parathyroid tests performed with use of single radioactive tracer, that require the acquisition of consecutive images of the patient, without altering his body position between successive stages of registration. This program allows for automation of previously time consuming procedures and thus saves time and decreases a risk of operator's errors. PMID- 26838948 TI - The validity of investigating occult hip fractures using multidetector CT. AB - OBJECTIVE: 10% of all hip fractures are occult on plain radiography, requiring further investigation to ascertain the diagnosis. MRI is presently the gold standard investigation, but frequently has disadvantages of time delay, resulting in increased hospital stay and mortality. Our aim was to establish whether multidetector CT (MDCT) is an appropriate first-line investigation of occult femoral neck (NOF) fractures. METHODS: From 2013, we elected to use MDCT as the first-line investigation in patients believed to have an NOF fracture with negative plain films. These were reported by consultant musculoskeletal radiologists. We retrospectively analysed the data of consecutive patients presenting to the University Hospital of Wales, over 30 months with a clinical suspicion of a hip fracture. RESULTS: 1443 patients were admitted during the study period. 209 (14.5%) patients had negative plain films requiring further investigation to exclude an NOF fracture, of which 199 patients had a CT. 93 patients had no fracture and 20 patients had isolated greater trochanter fractures. None of these patients progressed to develop an intracapsular femoral neck fracture at 4-month follow-up, although one patient sustained an extracapsular fracture following a high-energy fall whilst admitted. 26 femoral neck fractures were diagnosed on CT, whilst the remaining 60 patients were diagnosed with other pelvic ring fractures. CONCLUSION: When interpreted by experienced radiologists, MDCT has both sensitivity and specificity of 100%. ADVANCES IN KNOWLEDGE: We recommend the use of MDCT as a safe and appropriate first-line investigation for NOF fractures. PMID- 26838949 TI - An evaluation of ocular elasticity using real-time ultrasound elastography in primary open-angle glaucoma. AB - OBJECTIVE: The aim of this study was to compare sonoelastographic findings in the retina-choroid-sclera (RCS) complex and vitreous in glaucomatous and healthy eyes. METHODS: For this cross-sectional comparative study, 20 patients with primary open-angle glaucoma and 20 healthy volunteers were recruited. Ultrasound elastography measurements were taken with a sonographic scanner of the RCS complex, anterior vitreous (AV), posterior vitreous (PV), retrobulbar fat tissue (RFT), optic disc (OD) and optic nerve (ON) in each eye. RESULTS: The elasticity index of the RCS complex, RFT, OD, ON, AV and PV was similar in both groups (p > 0.05), although the AV/PV strain ratio in the group of patients with glaucoma was significantly higher (p = 0.04). CONCLUSION: Glaucoma increases the AV/PV strain ratio. In providing reproducible and consistent values, the real-time elastography (RTE) technique may be helpful in elucidating the mechanisms of glaucoma in some aspects. ADVANCES IN KNOWLEDGE: This study can help to evaluate the elasticity of the RCS complex and vitreous in glaucomatous eyes with RTE. PMID- 26838951 TI - A split-parotid delineation approach for dose optimization in volumetric modulated arc therapy for nasopharyngeal carcinoma patients with parapharyngeal space invasion and level IIa cervical lymph node involvements. AB - OBJECTIVE: This study evaluated the potential benefit of a split-parotid delineation approach on the parotid gland in the treatment planning of patients with nasopharyngeal carcinoma (NPC). METHODS: 50 patients with NPC with parapharyngeal space (PPS) and/or level IIa cervical node involvements were divided into three groups: PPS only, level IIa cervical node only and both. Two volumetric-modulated arc therapy plans were computed. The first plan (control) was generated based on the routine treatment-planning protocol, while the second plan (test) was computed with the split-parotid delineation approach, in which a line through the anterolateral margin of the retromandibular vein was created that divided the parotid gland into anterolateral and posteromedial subsegments. For the test plan, the anterolateral subsegment was prescribed, with a dose constraint of 25 Gy in the plan optimization. Dosimetric data of the parotid gland, target volumes and selected organs at risk (OARs) were compared between the control and test plans. RESULTS: The mean dose to the anterolateral subsegment of the parotid gland in all three groups was kept below 25 Gy. The test plan demonstrated significantly lower mean parotid dose than the control plan in the entire gland and the anterolateral subsegment in all three groups. The difference was the greatest in Group 3. CONCLUSION: The split-parotid delineation approach significantly lowered the mean dose to the anterolateral subsegment and overall gland without greatly compromising the doses to target volumes and other OARs. The effect was more obvious for both PPS and level IIa cervical node involvements than for either of them alone. ADVANCES IN KNOWLEDGE: It is the first article based on the assumption that parotid gland stem cells are situated at the anterolateral segment of the gland, and applied the split-parotid delineation approach to the parotid gland in the treatment planning of patients with NPC with PPS and level IIa cervical node involvements, so that the function of the post-radiotherapy parotid gland might be better preserved. PMID- 26838952 TI - Increased prevalence of tracheal diverticula in cystic fibrosis patients. AB - OBJECTIVE: This investigation sought to evaluate the prevalence and imaging characteristics of tracheal diverticula (TD) among patients with cystic fibrosis (CF). METHODS: A total of 113 patients with CF at our institution, with a median age of 29 years, had chest CT examinations between 2002 and 2014. These imaging studies were retrospectively reviewed to assess for the presence and characteristics of TD, including quantity, size and location. The severity of the CF disease was assessed using the Bhalla CT scoring system and pulmonary function tests. RESULTS: Of the 113 cases reviewed, 20 (17.7%) patients were found to have 1 or more TD. The presence of TD was associated with more severe disease by imaging criteria, with a Bhalla CT score of 13.9 +/- 4.3 in patients with TD and 11.5 +/- 4.3 in patients without TD. For the pulmonary function tests, forced expiratory volume in 1 s (FEV1) and FEV1 percent predicted demonstrated a trend towards worsening function in patients with TD, although the difference was not statistically significant. CONCLUSION: The prevalence of TD in our patient population with CF based on chest CT exams was 17.7%. In addition, the presence of TD was associated with more severe CF disease by imaging criteria. ADVANCES IN KNOWLEDGE: TD appear to have a higher prevalence in patients with CF than in the general population, are associated with more severe CF pulmonary disease by CT criteria and are frequently underreported by radiologists. PMID- 26838950 TI - Magnetic resonance imaging in lung: a review of its potential for radiotherapy. AB - MRI has superior soft-tissue definition compared with existing imaging modalities in radiation oncology; this has the added benefit of functional as well as anatomical imaging. This review aimed to evaluate the current use of MRI for lung cancer and identify the potential of a MRI protocol for lung radiotherapy (RT). 30 relevant studies were identified. Improvements in MRI technology have overcome some of the initial limitations of utilizing MRI for lung imaging. A number of commercially available and novel sequences have shown image quality to be adequate for the detection of pulmonary nodules with the potential for tumour delineation. Quantifying tumour motion is also feasible and may be more representative than that seen on four-dimensional CT. Functional MRI sequences have shown correlation with flu-deoxy-glucose positron emission tomography (FDG PET) in identifying malignant involvement and treatment response. MRI can also be used as a measure of pulmonary function. While there are some limitations for the adoption of MRI in RT-planning process for lung cancer, MRI has shown the potential to compete with both CT and PET for tumour delineation and motion definition, with the added benefit of functional information. MRI is well placed to become a significant imaging modality in RT for lung cancer. PMID- 26838953 TI - Volumetric modulated arc therapy (VMAT) in the combined modality treatment of anal cancer patients. AB - OBJECTIVE: To report clinical and dosimetric outcomes of a consecutive series of patients with anal cancer treated with volumetric-modulated arc therapy (VMAT) concomitant to chemotherapy (CT). METHODS: A cohort of 39 patients underwent VMAT employing a schedule consisting of 50.4 Gy/28 fractions to the gross tumour volume (GTV) and 42 Gy/28 fractions to the elective nodal volumes for patients with cT2N0 disease. Patients with cT3-T4/N0-N3 tumours were prescribed 54 Gy/30 fractions to the GTV and 50.4 Gy/30 fractions to the gross nodal volumes if sized <=3 cm or 54 Gy/30 fractions if > 3 cm. Elective nodal regions were given 45 Gy/30 fractions. CT was administered concurrently following Nigro's regimen. The primary end point was acute toxicity. Secondary end points were colostomy-free survival (CFS), disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS). Dosimetric data are also provided. RESULTS: Median follow up was 21 months. Maximum acute toxicities were: dermatologic-G3: 18%; gastrointestinal-G3: 5%; genitourinary-G3: 2%; anaemia-G2: 7%; leukopenia-G3: 28%; G4: 8%; neutropenia-G3: 13%; G4: 18%; thrombocytopenia-G3: 11%; and G4: 2%. The actuarial 2-year CFS was 77.9% [95% confidence interval (CI): 54-90.4%]. Actuarial 2-year OS and CSS were 85.2% (95% CI: 60.1-95.1%), while DFS was 75.1% (95% CI: 52.4.7-88.1%). CONCLUSION: Our clinical results support the use of VMAT as a safe and effective intensity-modulated radiotherapy (IMRT) option in the combined modality treatment of anal cancer, with consistent dosimetry, mild toxicity and promising sphincter preservation and survival rates. ADVANCES IN KNOWLEDGE: IMRT is a standard of care for patients with anal cancer, and VMAT is a robust technical solution in this setting. PMID- 26838954 TI - Prospective evaluation of free-breathing diffusion-weighted imaging for the detection of inflammatory bowel disease with MR enterography in childhood population. AB - OBJECTIVE: To evaluate prospectively the performance of diffusion-weighted imaging (DWI) for the detection of active lesions on MR enterography (MRE) in children with inflammatory bowel disease (IBD). METHODS: MRE of 48 children (mean age 13 years) with suspected or known IBD were blindly analysed by 2 independent readers for the presence of active lesions. Two sets of imaging including DWI and gadolinium-enhanced imaging (GEI) were reviewed. A reader consensus was obtained. The gold standard was histopathological findings. In patient-level analysis and segment-level analysis, sensitivity and specificity were calculated for DWI and GEI and compared using McNemar's test or logistic random-effects models. RESULTS: At least 1 active lesion was confirmed in 42 (87.5%) children. Sensitivity and specificity for the detection of at least one lesion were 88.1% (95% CI, 74.3 96.1) and 83.3% (95% CI, 35.9-99.6), respectively, for DWI and 66.7% (95% CI, 50.4-80.4) and 83.3% (95% CI, 35.9-99.6), respectively, for GEI. In segment-level analysis, sensitivity and specificity for the detection of specific segment lesions were 62.5% (95% CI, 48.1-75) and 97.1% (95% CI, 93.5-98.7), respectively, for DWI and 45.7% (95% CI, 30.8-61.3) and 98.2% (95% CI, 95.3-99.4), respectively, for GEI. The sensitivity of DWI was significantly better than that of GEI per patient (p = 0.004) and per segment (p = 0.028). CONCLUSION: DWI demonstrates better performance than GEI for the detection of active lesions in children with IBD. ADVANCES IN KNOWLEDGE: Examination with no intravenous injection-DWI can replace T1 weighted images when paediatric patients are screened with MRE for IBD. Examination performed in free breathing is better tolerated by children. PMID- 26838955 TI - Errors in imaging patients in the emergency setting. AB - Emergency and trauma care produces a "perfect storm" for radiological errors: uncooperative patients, inadequate histories, time-critical decisions, concurrent tasks and often junior personnel working after hours in busy emergency departments. The main cause of diagnostic errors in the emergency department is the failure to correctly interpret radiographs, and the majority of diagnoses missed on radiographs are fractures. Missed diagnoses potentially have important consequences for patients, clinicians and radiologists. Radiologists play a pivotal role in the diagnostic assessment of polytrauma patients and of patients with non-traumatic craniothoracoabdominal emergencies, and key elements to reduce errors in the emergency setting are knowledge, experience and the correct application of imaging protocols. This article aims to highlight the definition and classification of errors in radiology, the causes of errors in emergency radiology and the spectrum of diagnostic errors in radiography, ultrasonography and CT in the emergency setting. PMID- 26838957 TI - Periodic Functionalization of Surface-Confined Pores in a Two-Dimensional Porous Network Using a Tailored Molecular Building Block. AB - We present here the periodic functionalization of a two-dimensional (2D) porous molecular network using a tailored molecular building block. For this purpose, a dehydrobenzo[12]annulene (DBA) derivative, 1-isoDBA, having an isophthalic acid unit connected by an azobenzene linker to a C12 alkyl chain and five C14 chains, was designed and synthesized. After the optimization of monolayer preparation conditions at the 1,2,4-trichlorobezene (TCB)/graphite interface, scanning tunneling microscopy (STM) observation of the self-assembled monolayer of 1 isoDBA revealed the formation of extended domains of a porous honeycomb-type molecular network, which consists of periodically located nanowells each functionalized by a cyclic hexamer of hydrogen-bonded isophthalic acid units and those without functional groups. This result demonstrates that the present strategy based on precise molecular design is a viable route to site-specific functionalization of surface-confined nanowells. The nanowells of different size can be used for guest coadsorption of different guests, coronene COR and hexakis[4-(phenylethynyl)phenylethynyl]benzene HPEPEB, whose size and shape match the respective nanowells. STM observation of a ternary mixture (1 isoDBA/COR/HPEPEB) at the TCB/graphite interface revealed the site-selective immobilization of the two different guest molecules at the respective nanowells, producing a highly ordered three-component 2D structure. PMID- 26838956 TI - Changes in the T2 relaxation value of the tibiofemoral articular cartilage about 6 months after anterior cruciate ligament reconstruction using the double-bundle technique. AB - OBJECTIVE: To evaluate T2 relaxation values (T2RVs) of knee joint cartilage after double-bundle anterior cruciate ligament reconstruction (DB-ACLR) in a 6-month follow-up and to correlate changes between T2RVs with meniscal status and clinical findings. METHODS: 27 patients who underwent DB-ACLR and MRI before and 6 months after surgery, and 27 control subjects were enrolled. We compared T2RVs of the control vs pre-operative MR and pre-operative vs post-operative MR using 28 subcompartments, including superficial and deep layers. Correlations between T2RV changes with meniscal status and clinical data were examined. RESULTS: The pre-operative T2RV was significantly higher than that of the control group in the medial tibia (posterior-superficial), posterior medial femur (superficial) and posterior lateral femur (superficial and deep). The post-operative T2RV was significantly higher than that of pre-operative T2RV in the posterior medial femur (superficial), medial tibia (anterior-deep and central-deep), lateral femur (anterior-deep, anterior-superficial and central-superficial) and posterior medial femur (deep). Moderate positive correlations between pre-operative and post-operative T2RV changes were found at the posterior medial femur (interval between injury and MR examination, and instability) and posterior lateral femur (Lysholm score). CONCLUSION: Patients with anterior cruciate ligament injury followed by DB-ACLR presented short-term subcompartment T2RV changes at the medial femur, lateral femur and medial tibia. Meniscal status did not affect T2RV; however, clinical findings influenced T2RV at the posterior grooves of the medial and lateral femoral condyles. ADVANCES IN KNOWLEDGE: Patients submitted to DB-ACLR presented T2RV changes in both femoral and medial tibial condyles 6 months after the surgery, affecting not just the weight-bearing areas, but also the less-weight-bearing areas. PMID- 26838958 TI - Atomic structures and oxygen dynamics of CeO2 grain boundaries. AB - Material performance is significantly governed by grain boundaries (GBs), a typical crystal defects inside, which often exhibit unique properties due to the structural and chemical inhomogeneity. Here, it is reported direct atomic scale evidence that oxygen vacancies formed in the GBs can modify the local surface oxygen dynamics in CeO2, a key material for fuel cells. The atomic structures and oxygen vacancy concentrations in individual GBs are obtained by electron microscopy and theoretical calculations at atomic scale. Meanwhile, local GB oxygen reduction reactivity is measured by electrochemical strain microscopy. By combining these techniques, it is demonstrated that the GB electrochemical activities are affected by the oxygen vacancy concentrations, which is, on the other hand, determined by the local structural distortions at the GB core region. These results provide critical understanding of GB properties down to atomic scale, and new perspectives on the development strategies of high performance electrochemical devices for solid oxide fuel cells. PMID- 26838960 TI - Biomarkers detect involvement of acute myocardial injury in a paediatric haemolytic-uraemic syndrome patient. AB - Although extrarenal manifestations of haemolytic-uraemic syndrome are not frequent, myocardial dysfunction should be given special consideration because of the importance of proper early haemodynamic management and potential complications. We report the case of a 21-month-old child with haemolytic-uraemic syndrome who developed clinical signs of poor myocardial function with depressed myocardial function noted by bedside echocardiography and significant elevation of biomarkers. Early intervention and supportive treatment for the patient were crucial during the acute phase of cardiac failure, and repeated monitoring of biomarkers and ecocardiography were useful diagnostic tools that provided relevant information throughout the patient's evolution. PMID- 26838961 TI - Computed Tomography and MRI of the Hepatobiliary System and Pancreas. AB - MRI and computed tomographic (CT) imaging are becoming more common in the diagnosis of hepatobiliary and pancreatic disorders in small animals. With the advent of multislice CT scanners, sedated examinations in veterinary patients are feasible increasing the use of this imaging modality. CT and MRI provide additional information for dogs and cats with hepatobiliary and pancreatic diseases because of lack of superimposition of structures, operator dependence, and through intravenous contrast administration. This added value provides more information for diagnosis, prognosis, and surgical planning. PMID- 26838959 TI - Interventions to increase HPV vaccination coverage: A systematic review. AB - We reviewed intervention studies designed to increase human papillomavirus (HPV) vaccination coverage to further understand the impact interventions can have on HPV vaccination coverage. We searched 5 databases for intervention studies published from June 2006 to May 2015. Studies were included if they quantitatively measured HPV vaccination coverage as an outcome and were conducted in the United States. We abstracted outcomes, methods, and results from each study and classified by type of intervention conducted. Findings from 34 studies suggest many types of intervention strategies can increase HPV vaccination coverage in different settings, and with modest cost. Interventions were effective especially when implemented in combination at both provider and community levels. However, not all interventions showed significant effects on coverage. More research is needed to identify the best methods for widespread implementation of effective strategies. PMID- 26838963 TI - Solvent Effects on the Reactions of the Nerve Agent VX with KF/Al2O3: Heterogeneous or Homogeneous Decontamination? AB - Solvent effects on the reactions of the extremely toxic nerve agent VX with KF/Al2O3 powder were explored. Small quantities of water or methanol (5-10 wt %), which effectively mobilized all components while maintaining the heterogeneous nature of the reaction, promoted much faster rates than those obtained with larger quantities. Any amount of acetonitrile resulted in extremely slow transformations. Surprisingly, 5-50 wt % of heptane led to fast reactions due to the combination of its ability to mediate fast diffusion of VX and a MAS centrifugation effect. PMID- 26838962 TI - Extended criteria donors in liver transplantation Part I: reviewing the impact of determining factors. AB - The definition and factors of extended criteria donors have already been set; however, details of the various opinions still differ in many respects. In this review, we summarize the impact of these factors and their clinical relevance. Elderly livers must not be allocated for hepatitis C virus (HCV) positives, or patients with acute liver failure. In cases of markedly increased serum transaminases, donor hemodynamics is an essential consideration. A prolonged hypotension of the donor does not always lead to an increase in post transplantation graft loss if post-OLT care is proper. Hypernatremia of less than 160 mEq/L is not an absolute contraindication to accept a liver graft per se. The presence of steatosis is an independent and determinant risk factor for the outcome. The gold standard of the diagnosis is the biopsy. This is recommended in all doubtful cases. The use of HCV+ grafts for HCV+ recipients is comparable in outcome. The leading risk factor for HCV recurrence is the actual RNA positivity of the donor. The presence of a proper anti-HBs level seems to protect from de novo HBV infection. A favourable outcome can be expected if a donation after cardiac death liver is transplanted in a favourable condition, meaning, a warm ischemia time < 30 minutes, cold ischemia time < 8-10 hours, and donor age 50-60 years. The pathway of organ quality assessment is to obtain the most relevant information (e.g. biopsy), consider the co-existing donor risk factors and the reserve capacity of the recipient, and avoid further technical issues. PMID- 26838964 TI - A flexible, transparent and super-long-life supercapacitor based on ultrafine Co3O4 nanocrystal electrodes. AB - Flexible and transparent supercapacitors, as advanced energy storage devices, are essential for the development of innovative wearable electronics because of their unique optical and mechanical qualities. However, all previous designs are based on carbon-based nanostructures like carbon nanotubes and graphene, and these devices usually have poor or short cycling lives. Here, we demonstrate a high performance, flexible, transparent, and super-long-life supercapacitor made from ultrafine Co3O4 nanocrystals synthesized using a novel process involving laser ablation in liquid. The fabricated flexible and transparent pseudocapacitor exhibits a high capacitance of 177 F g(-1) on a mass basis and 6.03 mF cm(-2) based on the area of the active material at a scan rate of 1 mV s(-1), as well as a super-long cycling life with 100% retention rate after 20 000 cycles. An optical transmittance of up to 51% at a wavelength of 550 nm is achieved, and there are not any obvious changes in the specific capacitance after bending from 0 degrees to 150 degrees , even after bending over 100 times. The integrated electrochemical performance of the Co3O4-based supercapacitor is greatly superior to that of the carbon-based ones reported to date. These findings open the door to applications of transition metal oxides as advanced electrode materials in flexible and transparent pseudocapacitors. PMID- 26838965 TI - Isolation of a pH-Sensitive IgNAR Variable Domain from a Yeast-Displayed, Histidine-Doped Master Library. AB - In recent years, engineering of pH-sensitivity into antibodies as well as antibody-derived fragments has become more and more attractive for biomedical and biotechnological applications. Herein, we report the isolation of the first pH sensitive IgNAR variable domain (vNAR), which was isolated from a yeast displayed, semi-synthetic master library. This strategy enables the direct identification of pH-dependent binders from a histidine-enriched CDR3 library. Displayed vNAR variants contained two histidine substitutions on average at random positions in their 12-residue CDR3 loop. Upon screening of seven rounds against the proof-of-concept target EpCAM (selection for binding at pH 7.4 and decreased binding at pH 6.0), a single clone was obtained that showed specific and pH-dependent binding as characterized by yeast surface display and biolayer interferometry. Potential applications for such pH-dependent vNAR domains include their employment in tailored affinity chromatography, enabling mild elution protocols. Moreover, utilizing a master library for the isolation of pH-sensitive vNAR variants may be a generic strategy to obtain binding entities with prescribed characteristics for applications in biotechnology, diagnostics, and therapy. PMID- 26838967 TI - Effect of Age on Postoperative Outcomes Following Total Knee Arthroplasty. AB - The demand for total knee arthroplasty (TKA) continues to grow exponentially, and this has been attributed to a higher prevalence of osteoarthritis and excellent procedural success. In particular, with increasing life expectancies and obesity rates, surgeons are seeing patients with a wider age range. Therefore, we assessed the effects of patient age on: (1) range of motion (ROM); (2) pain and function; (3) physical and mental status; and (4) activity levels following TKA. We assessed 278 TKA patients (108 men, 170 women), with subdivision into three age-specific groups: < 55, 55 to 74, and 75 years or older. ROM was assessed and functional outcomes were evaluated using the Knee Society scoring (KSS) system, the short form-36 (SF-36), and the lower extremity activity scale (LEAS). The patients were assessed preoperatively and postoperatively at 6 weeks, 3 months, 12 months, and then yearly thereafter until 7 years. All cohorts demonstrated improvements in ROM, with no significant differences between the age groups. For KSS objective, there were no significant differences between groups after 6-week follow-up, though in pain and motion, the 75 years and older had the highest mean score at final follow-up (97 points). In KSS function, the < 55 years group had highest scores at 2 (90 vs. 87 vs. 75 points) and 5-year follow-up (96 vs. 88 vs. 72 points). For SF-36 and LEAS, the 75 year and older cohorts had the lowest mean scores at various time points. In the mental component, those < 55 years had the lowest scores postoperatively. It is important to understand the effect of age on post-TKA outcomes, particularly as the cohort of these patients continues to grow. Our results demonstrate that comprehensive preoperative discussions and management are needed, particularly in those patients at either end of the age spectrum (< 55 or >= 75 years). PMID- 26838968 TI - Correlations between Navigation and Radiographic Measures of Alignment. AB - This study was designed to compare the correlations between intraoperative navigation and radiographic alignment in patients who underwent total knee arthroplasty (TKA) and open wedge high tibial osteotomy (HTO). The reliability of navigation and radiographic alignment before and after surgery was compared in 82 prospectively enrolled patients who underwent open wedge HTO and 91 knees that underwent TKA. The absolute difference in preoperative mechanical axis (MA) between navigation and radiography was 1.1 degrees greater in the TKA than in the HTO group (2.6 vs. 1.5 degrees, p < 0.001). Postoperatively, however, the absolute difference between navigation and radiographic measurements of MA was 1 degree greater in the HTO than in the TKA group (2.4 vs. 1.4 degrees, p < 0.001). The percentage of outliers, defined as a >3 degrees difference between navigation and radiographic MA, was significantly greater preoperatively in the TKA group (37 vs. 10%, p < 0.001), but significantly greater postoperatively in the HTO group (28 vs. 10%, p < 0.001). The discrepancy between navigation and radiographic measurement of coronal alignment was significantly greater preoperatively in the TKA than in the HTO group, whereas the discrepancy was significantly greater postoperatively in the HTO group. PMID- 26838966 TI - Zebrafish Embryo Toxicity Microscale Model for Ichthyotoxicity Evaluation of Marine Natural Products. AB - Marine organisms often protect themselves against their predators by chemical defensive strategy. The second metabolites isolated from marine organisms and their symbiotic microbes have been proven to play a vital role in marine chemical ecology, such as ichthyotoxicity, allelopathy, and antifouling. It is well known that the microscale models for marine chemoecology assessment are urgently needed for trace quantity of marine natural products. Zebrafish model has been widely used as a microscale model in the fields of environment ecological evaluation and drug safety evaluation, but seldom reported for marine chemoecology assessment. In this work, zebrafish embryo toxicity microscale model was established for ichthyotoxicity evaluation of marine natural products by using 24-well microplate based on zebrafish embryo. Ichthyotoxicity was evaluated by observation of multiple toxicological endpoints, including coagulation egg, death, abnormal heartbeat, no spontaneous movement, delayed hatch, and malformation of the different organs during zebrafish embryogenesis periods at 24, 48, and 72 h post fertilization (hpf). 3,4-Dichloroaniline was used as the positive control for method validation. Subsequently, the established model was applied to test the ichthyotoxic activity of the compounds isolated from corals and their symbiotic microbes and to isolate the bioactive secondary metabolites from the gorgonian Subergorgia mollis under bioassay guidance. It was suggested that zebrafish embryo toxicity microscale model is suitable for bioassay-guided isolation and preliminary bioactivity screening of marine natural products. PMID- 26838969 TI - Analysis of Knee Joint Line Obliquity after High Tibial Osteotomy. AB - The aim of this study was to evaluate which lower extremity alignment (knee and ankle joint) parameters affect knee joint line obliquity (KJLO) in the coronal plane after open wedge high tibial osteotomy (OWHTO). Overall, 69 knees of patients that underwent OWHTO were evaluated using radiographs obtained preoperatively and from 6 weeks to 3 months postoperatively. We measured multiple parameters of knee and ankle joint alignment (hip-knee-ankle angle [HKA], joint line height [JLH], posterior tibial slope [PS], femoral condyle-tibial plateau angle [FCTP], medial proximal tibial angle [MPTA], mechanical lateral distal femoral angle [mLDFA], KJLO, talar tilt angle [TTA], ankle joint obliquity [AJO], and the lateral distal tibial ground surface angle [LDTGA]; preoperative [-pre], postoperative [-post], and the difference between -pre and -post values [ Delta]). We categorized patients into two groups according to the KJLO-post value (the normal group [within +/- 4 degrees, 56 knees] and the abnormal group [greater than +/- 4 degrees, 13 knees]), and compared their -pre parameters. Multiple logistic regression analysis was used to examine the contribution of the -pre parameters to abnormal KJLO-post. The mean HKA-Delta (-9.4 +/- 4.7 degrees) was larger than the mean KJLO-Delta (-2.1 +/- 3.2 degrees). The knee joint alignment parameters (the HKA-pre, FCTP-pre) differed significantly between the two groups (p < 0.05). In addition, the HKA-pre (odds ratio [OR] = 1.27, p = 0.006) and FCTP-pre (OR = 2.13, p = 0.006) were significant predictors of abnormal KJLO-post. However, -pre ankle joint parameters (TTA, AJO, and LDTGA) did not differ significantly between the two groups and were not significantly associated with the abnormal KJLO-post. The -pre knee joint alignment and knee joint convergence angle evaluated by HKA-pre and FCTP-pre angle, respectively, were significant predictors of abnormal KJLO after OWHTO. However, -pre ankle joint parameters were not significantly associated with abnormal KJLO after OWHTO. PMID- 26838970 TI - Knee Dislocation in the Morbidly Obese Patient. AB - Though a relatively rare orthopedic injury, knee dislocation in the morbidly obese population has been increasingly reported in the literature. These injuries are often referred to as "ultralow-velocity knee dislocations" since they commonly occur after a seemingly trivial injury, such as a ground level fall. As a result, these injuries are often underappreciated and initially misdiagnosed. Even though these injuries are low-velocity, they should still be regarded as a high energy injury because of the large amount of mass contributing to the dislocating force. Knee dislocations in the morbidly obese are associated with a particularly high rate of neurovascular injury. A timely and accurate diagnosis is crucial to avoid serious limb-threatening complications, including the need for amputation. Therefore, evaluating physicians should maintain a high suspicion for a knee dislocation in any morbidly obese patient who presents with knee pain following a seemingly innocuous injury. Management of these injuries is controversial. Associated vascular injuries must be identified promptly and appropriately managed by a vascular surgery team. There is no consensus on the ideal orthopedic treatment of knee dislocations in the morbidly obese patient. Operative treatment can be fraught with complications, including a higher rate of neurovascular injury, increased surgical complications, and poor subjective patient outcome scores compared with nonobese patients sustaining a high-velocity knee dislocation. It is paramount that treating physicians are familiar with the unique challenges of treating knee dislocations in the morbidly obese patient when discussing risks and benefits of treatment options. This article presents a review of the existing literature on knee dislocations in the morbidly obese population, including diagnosis, management, and outcomes. PMID- 26838972 TI - Pediatric Cholestatic Disorders: Approach to Pathologic Diagnosis. AB - This article addresses select liver diseases that are commonly seen in the pediatric group and pose diagnostic challenges in practice. The key genetic/molecular abnormalities, clinical features, histopathologic findings, diagnostic modalities, differential diagnoses, and possible pitfalls in diagnosis are discussed in detail. Although recent advances in understanding the pathophysiology of bile synthesis and transport along with advances in molecular genetics have allowed a better characterization of many of these liver diseases, significant overlap in the histopathologic features of many of these disorders still leads to diagnostic challenges for the pathologist. PMID- 26838971 TI - Liposomal Bupivacaine Suspension Can Reduce Lengths of Stay and Improve Discharge Status of Patients Undergoing Total Knee Arthroplasty. AB - The purpose of this study was to use a large hospital database to assess: (1) length of hospital stay (LOS) and (2) discharge status among patients undergoing total knee arthroplasty (TKA) with or without the use of a liposomal bupivacaine suspension injection. We utilized an all-payer hospital administrative database from July 1, 2013 to June 30, 2014. We then selected patients age 18 years or older who had an inpatient stay for TKA in the data window based on International Classification of Diseases, Ninth Revision (ICD-9) procedure codes (ICD-9-CM = 81.54), which resulted in 103,152 TKA patients. Patients who had nerve blocks were excluded, which resulted in 94,828 TKA patients. The TKA cohort who received a liposomal bupivacaine suspension consisted of 14,668 patients (9,211 females; 5,457 males) who had a mean age of 66 years, while the TKAs without injections or block consisted of 80,160 patients (49,699 females; 30,461 males) who had a mean age of 66 years. Analyses of LOS were performed using a linear model, controlling for age, sex, race, region, Charlson index, and operating time. Discharge status to home versus rehabilitation or short-term nursing facility was evaluated using logistic regression analysis controlling for the above covariates. The adjusted mean LOS for the injection cohort was significantly shorter at 2.58 days compared with 2.98 days in the no injection cohort. The unadjusted distribution of patients being discharged to home compared with short-term nursing facility or rehabilitation was higher in the injection cohort compared with the cohort who did not receive injections (73.2 vs. 66.6%). Logistic regression analysis demonstrated that there was a higher likelihood of being discharged to home with liposomal bupivacaine. Patients who underwent TKA with liposomal bupivacaine had a significantly shorter LOS and a higher likelihood of being discharged to home. These results suggest that liposomal bupivacaine may represent a promising addition to current pain management regimens. Furthermore, it may limit pain following surgery, which may allow patients to ambulate earlier and have improved outcomes. PMID- 26838973 TI - Nonalcoholic Steatohepatitis: Diagnostic Challenges. AB - This article reviews diagnostic criteria for nonalcoholic steatohepatitis (NASH), current grading and staging methodology, and diagnostic challenges and pitfalls in routine practice. Current practice guidelines and prognostic and treatment considerations are discussed. The clinical diagnosis of nonalcoholic fatty liver disease may represent stable disease without progressive liver damage, in the form of nonalcoholic fatty liver (NAFL), or aggressive disease that will progress to advanced fibrosis, in the form of NASH. NASH is diagnosed from a liver biopsy after assessment by a pathologist to distinguish NASH from NAFL (and other histologic mimics of NASH); this distinction is critical for patient management. PMID- 26838974 TI - Autoimmune Hepatitis. AB - Autoimmune hepatitis is a chronic necroinflammatory disease of unknown etiology that is characterized by increased aminotransferases, serum autoantibodies, increased immunoglobulin G levels, and histological interface hepatitis. The disease does not have a pathognomonic clinical, laboratory, or histological feature; diagnosis depends on a combination of clinical and pathologic criteria which also form the basis for a weighted scoring system to aid diagnosis. Liver biopsy is an essential part of the diagnostic criteria and is also crucial to the management of the disease. This review focuses on the diagnosis, microscopic features, differential diagnosis and overlap syndromes of autoimmune hepatitis. PMID- 26838975 TI - Liver Transplant Pathology: Review of Challenging Diagnostic Situations. AB - Histopathologic assessment of allograft liver biopsies has an important role in managing patients who have undergone liver transplantation. In this review, several topics are discussed that create diagnostic problems in transplant pathology, with emphasis on pathologic features and differential diagnosis. The topics discussed are acute cellular rejection, late acute rejection (centrizonal/parenchymal rejection), chronic rejection, plasma cell hepatitis, idiopathic posttransplant chronic hepatitis, fibrosing cholestatic hepatitis, selected viral infections (cytomegalovirus, Epstein-Barr virus, and hepatitis E), and acute antibody-mediated rejection. PMID- 26838976 TI - Cirrhosis Regression and Subclassification. AB - The end point of liver fibrosis in almost all chronic liver diseases is cirrhosis. Progression to cirrhosis is accompanied by vascular remodeling and regeneration with important functional and hemodynamic consequences that include development of portal hypertension and eventually decompensation and death. Fibrosis can regress following successful treatment of the underlying disease. However, most common fibrosis scoring systems are not equipped for assessing this aspect. Nodule size, septal width and fibrosis area seem to correlate with disease severity and progression in cirrhosis. Classification systems based on nodule size, septal width, and fibrosis area need to be further validated. PMID- 26838977 TI - Hepatocellular Adenomas: WHO Classification and Immunohistochemical Workup. AB - This review discusses the various subtypes of hepatocellular adenomas (HCAs), their diagnosis, and management. HCAs are benign tumors, mostly seen in young women in a normal background liver. Recent advances in understanding HCA pathogenesis and molecular alterations led to recognition of different subtypes, now included in the WHO classification. Complications include hemorrhage and rarely malignant transformation into hepatocellular carcinoma. Diagnosis and differentiation are challenging, requiring careful attention to clinical setting, histology, and immuostaining profile. Risk of complications varies depending on the HCA; hence, subtyping has clinical significance and is performed based on morphology and use of selected immunohistochemical markers. PMID- 26838978 TI - Diagnostic Approach to Hepatic Mass Lesions and Role of Immunohistochemistry. AB - This review provides an overview of various hepatic mass lesions and a practical diagnostic approach, including most recent immunohistochemical stains used in clinical practice. A wide variety of benign and malignant lesions present as hepatic masses, and the differential diagnosis varies. In cirrhotic liver, the commonest malignant tumor is hepatocellular carcinoma (HCC), which needs to be differentiated from macroregenerative nodules, dysplastic nodules, and other tumors. The differential diagnosis of lesions in noncirrhotic liver in younger patients includes hepatic adenoma (HA), focal nodular hyperplasia (FNH), HCC, and other primary hepatic neoplasms and metastases. In older populations, metastases remain the most common mass lesions. PMID- 26838979 TI - Hepatocellular Carcinoma: Histologic Subtypes. AB - This review discusses the various histologic subtypes of hepatocellular carcinoma (HCC), focusing on their clinical features, pathologic features, immunohistochemical profiles, differential diagnosis, prognosis, and clinical relevance of diagnosis. The WHO recognized variants of scirrhous HCC, fibrolamellar carcinoma, combined HCC-cholangiocarcinoma (HCC-CC), sarcomatoid HCC, undifferentiated carcinoma, and lymphoepithelioma-like HCC are discussed in detail. Other subtypes including clear cell HCC, diffuse cirrhosis-like HCC, steatohepatitic HCC, transitional liver cell tumor, and CAP carcinoma are also reviewed. PMID- 26838980 TI - Liver Pathology: Unraveling the Art of Pattern Recognition. PMID- 26838981 TI - GPs will consider "mass resignation" if government ignores crisis. PMID- 26838983 TI - Authors' Reply to Li: The Effects of Body Mass on Optimal Load for Power During Resistance Training. PMID- 26838986 TI - Erratum to: How Much Clinical and Functional Impairment do Children Treated With Knee Rotationplasty Experience in Adulthood? PMID- 26838982 TI - Reward functions of the basal ganglia. AB - Besides their fundamental movement function evidenced by Parkinsonian deficits, the basal ganglia are involved in processing closely linked non-motor, cognitive and reward information. This review describes the reward functions of three brain structures that are major components of the basal ganglia or are closely associated with the basal ganglia, namely midbrain dopamine neurons, pedunculopontine nucleus, and striatum (caudate nucleus, putamen, nucleus accumbens). Rewards are involved in learning (positive reinforcement), approach behavior, economic choices and positive emotions. The response of dopamine neurons to rewards consists of an early detection component and a subsequent reward component that reflects a prediction error in economic utility, but is unrelated to movement. Dopamine activations to non-rewarded or aversive stimuli reflect physical impact, but not punishment. Neurons in pedunculopontine nucleus project their axons to dopamine neurons and process sensory stimuli, movements and rewards and reward-predicting stimuli without coding outright reward prediction errors. Neurons in striatum, besides their pronounced movement relationships, process rewards irrespective of sensory and motor aspects, integrate reward information into movement activity, code the reward value of individual actions, change their reward-related activity during learning, and code own reward in social situations depending on whose action produces the reward. These data demonstrate a variety of well-characterized reward processes in specific basal ganglia nuclei consistent with an important function in non motor aspects of motivated behavior. PMID- 26838984 TI - Skeletal Muscle Loading Changes its Regenerative Capacity. AB - Whenever skeletal muscle insults occur, both by functional impositions or other injury forms, skeletal muscle repair (SMR) follows. The SMR succeeds when proper skeletal muscle regeneration and limited fibrosis ensue. Muscle fiber replenishment by fibrosis negatively affects the tissue quality and functionality and, furthermore, represents the worst post-injury phenotypic adaptation. Acute muscle injury treatment commonly follows the RICE method-rest, ice, compression, and elevation. This immediate immobilization seems to be beneficial to preserving the tissue structure and avoiding further destruction; however, if these interventions are delayed, the risk of muscle atrophy and its deleterious-related effects increase, with resultant impaired SMR. Moreover, a growing body of evidence shows positive skeletal muscle loading (SML) effects during SMR since it seems to effectively increase satellite cells (SCs) in their activation, proliferation, self-renewal, and differentiation capacities. Additionally, recent data show that SML may also influence the functions of other participants in SMR, compelling SMR to achieve less fibrotic accretion and accelerated muscle mass recovery. Moreover, given the SML effects on SCs, it is plausible to consider that these can increase the myofibers' basal myogenic potential. Thus, it seems relevant to scrutinize the possible acute and chronic SML therapeutic and prophylactic effects regarding the SMR process. PMID- 26838987 TI - Human kidney proximal tubule cells are vulnerable to the effects of Rauwolfia serpentina. AB - Rauwolfia serpentina (or Snake root plant) is a botanical dietary supplement marketed in the USA for maintaining blood pressure. Very few studies have addressed the safety of this herb, despite its wide availability to consumers. Its reported pleiotropic effects underscore the necessity for evaluating its safety. We used a human kidney cell line to investigate the possible negative effects of R. serpentina on the renal system in vitro, with a specific focus on the renal proximal tubules. We evaluated cellular and mitochondrial toxicity, along with a variety of other kidney-specific toxicology biomarkers. We found that R. serpentina was capable of producing highly detrimental effects in our in vitro renal cell system. These results suggest more studies are needed to investigate the safety of this dietary supplement in both kidney and other target organ systems. PMID- 26838988 TI - Are Quality Improvement Collaboratives the Way Forward in Peritoneal Dialysis? PMID- 26838989 TI - Anders Tranaeus (1946 - 2015). PMID- 26838990 TI - United Kingdom Survey of Culture-Negative Peritonitis and Dialysate Sampling Practice. AB - Peritonitis is a major cause of technique failure in peritoneal dialysis (PD) and accurate diagnosis ensures successful management and avoids unnecessary antibiotic exposure. United Kingdom (UK) registry data on peritonitis rates are not routinely reported. We conducted an electronic survey amongst senior PD nurses and microbiologists to obtain information about PD effluent sampling and processing practices in the UK. The survey was completed by 53 of 79 centres (67% response rate). The median annual culture-negative rate was 15% (range 5 - 38%). The main findings were wide variation in reported sampling volumes and processing methods that may in part explain the variation in culture-negative rates. Adherence to guidelines might reduce culture-negative rates informed by reporting data into national registries. PMID- 26838985 TI - The Importance of Muscular Strength in Athletic Performance. AB - This review discusses previous literature that has examined the influence of muscular strength on various factors associated with athletic performance and the benefits of achieving greater muscular strength. Greater muscular strength is strongly associated with improved force-time characteristics that contribute to an athlete's overall performance. Much research supports the notion that greater muscular strength can enhance the ability to perform general sport skills such as jumping, sprinting, and change of direction tasks. Further research indicates that stronger athletes produce superior performances during sport specific tasks. Greater muscular strength allows an individual to potentiate earlier and to a greater extent, but also decreases the risk of injury. Sport scientists and practitioners may monitor an individual's strength characteristics using isometric, dynamic, and reactive strength tests and variables. Relative strength may be classified into strength deficit, strength association, or strength reserve phases. The phase an individual falls into may directly affect their level of performance or training emphasis. Based on the extant literature, it appears that there may be no substitute for greater muscular strength when it comes to improving an individual's performance across a wide range of both general and sport specific skills while simultaneously reducing their risk of injury when performing these skills. Therefore, sport scientists and practitioners should implement long-term training strategies that promote the greatest muscular strength within the required context of each sport/event. Future research should examine how force-time characteristics, general and specific sport skills, potentiation ability, and injury rates change as individuals transition from certain standards or the suggested phases of strength to another. PMID- 26838991 TI - Dialysis-Associated Telangiectasia: Case Report and Review of the Literature. AB - Patients with end-stage renal disease (ESRD) are at an increased risk of bleeding. We report the case of a 40-year-old female, on peritoneal dialysis for ESRD, who presented with profound anemia; she was later found to have a bleeding jejunal dialysis-associated telangiectasia. We review the literature published to date on dialysis-associated telangiectasia and discuss the possible underling etiologies. PMID- 26838992 TI - First Report of Laribacter hongkongensis Peritonitis in Continuous Ambulatory Peritoneal Dialysis. AB - The most common pathogens associated with peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) are gram-positive bacteria, which constitute 60 - 80% of all isolates. With the advancement of molecular technologies for bacterial identification, cases of CAPD-related peritonitis caused by bacteria previously not known to be associated with this clinical condition have been reported. Here we report the first case of CAPD-related peritonitis due to Laribacter hongkongensis. PMID- 26838993 TI - Pharmacokinetic and Dynamic of Furosemide in Peritoneal Dialysis Patients. AB - The aim of our study was to evaluate the efficacy and bioavailibility of a commonly used oral furosemide dose (500 mg) compared to a 250 mg intravenous (IV) dose in PD patients with significant residual renal function (urine volume > 100 mL). We also evaluated the immediate blood pressure effect in these patients. The data were obtained from a study we performed for the homologation of a 500-mg dose of furosemide by Health Canada. PMID- 26838994 TI - Sleep-Disordered Breathing in 2 Pediatric Patients on Peritoneal Dialysis. AB - Sleep-disordered breathing (SDB) is prevalent in children with chronic kidney disease (CKD), and has the potential to worsen vascular and neuro-cognitive health and quality of life. We present 2 children with CKD who experience central sleep apnea and nocturnal hypoventilation and discuss the possible underlying mechanisms in relation to CKD and dialysis. PMID- 26838995 TI - Laparoscopic Intraperitonealization of Accidentally Misplaced Peritoneal Dialysis Catheter: A Salvage Procedure. AB - Tenckhoff catheter placement is a well-established procedure to facilitate continuous ambulatory peritoneal dialysis (CAPD) in end-stage renal disease (ESRD) management. Catheter malposition is a possible cause of catheter malfunction. Options to deal with early malfunction are re-exploration, omentectomy, repositioning, or new catheter placement. Technical malpositioning can be dealt with early, with minimal morbidity and cost. Here we report a case of a CAPD catheter accidentally placed preperitoneally which was salvaged using videolaparscopy. PMID- 26838996 TI - Successful Treatment of a Pacemaker Infection with Intraperitoneal Daptomycin. AB - We investigated the pharmacokinetics of intraperitoneal administration of daptomcyin in a peritoneal dialysis (PD) patient treated for a pacemaker infection with Staphylococcus epidermidis. After initial start of intravenous daptomycin at 9 mg/kg body weight every 48 hours, the therapy was switched to intraperitoneal administration of 5.3 mg/kg body weight in 1 L icodextrin 7.5% with a dwell time of 12 hours overnight every 48 hours. Therapeutic drug monitoring (TDM) was performed at 4 hours and 24 hours after dose administration. Due to high peak concentration above target peak concentration, the dose was reduced to a final maintenance dose of 3.2 mg/kg body weight. Data from this single case suggest that serum drug concentration above the minimal inhibitory concentration (MIC) can be easily achieved with intraperitoneal administration of daptomycin every 48 hours even with a lower dose, as recommended for the intravenous administration, but measurement of serum concentration and dose adjustments are mandatory in such cases. PMID- 26838997 TI - Gene Therapy Strategies for Alzheimer's Disease: An Overview. AB - Key neuropathological hallmarks of Alzheimer's disease (AD) are extracellular amyloid plaques and intracellular accumulation of hyperphosphorylated Tau protein. The mechanisms underlying these neuropathological changes remain unclear. So far, research on AD therapy has had limited success in terms of symptomatic treatments although it has also had several failures for disease modifying drugs. Gene transfer strategies to the brain have contributed to evaluate in animal models many interesting tracks, some of which should deserve clinical applications in AD patients in the future. PMID- 26838998 TI - Exercise and fall prevention self-management to reduce mobility-related disability and falls after fall-related lower limb fracture in older people: protocol for the RESTORE (Recovery Exercises and STepping On afteR fracturE) randomised controlled trial. AB - BACKGROUND: Lasting disability and further falls are common and costly problems in older people following fall-related lower limb and pelvic fractures. Exercise interventions can improve mobility after fracture and reduce falls in older people, however the optimal approach to rehabilitation after fall-related lower limb and pelvic fracture is unclear. This randomised controlled trial aims to evaluate the effects of an exercise and fall prevention self-management intervention on mobility-related disability and falls in older people following fall-related lower limb or pelvic fracture. Cost-effectiveness of the intervention will also be investigated. METHODS/DESIGN: A randomised controlled trial with concealed allocation, assessor blinding for physical performance tests and intention-to-treat analysis will be conducted. Three hundred and fifty people aged 60 years and over with a fall-related lower limb or pelvic fracture, who are living at home or in a low care residential aged care facility and have completed active rehabilitation, will be recruited. Participants will be randomised to receive a 12-month intervention or usual care. The intervention group will receive ten home visits from a physiotherapist to prescribe an individualised exercise program with motivational interviewing, plus fall prevention education through individualised advice from the physiotherapist or attendance at the group based "Stepping On" program (seven two-hour group sessions). Participants will be followed for a 12-month period. Primary outcome measures will be mobility-related disability and falls. Secondary outcomes will include measures of balance and mobility, falls risk, physical activity, walking aid use, frailty, pain, nutrition, falls efficacy, mood, positive and negative affect, quality of life, assistance required, hospital readmission, and health-system and community service contact. DISCUSSION: This study will determine the effect and cost effectiveness of this exercise self management intervention on mobility-related disability and falls in older people who have recently sustained a fall-related lower limb or pelvic fracture. The results will have implications for the design and implementation of interventions for older people with fall related lower limb fractures. The findings of this study will be disseminated in peer-reviewed journals and through professional and scientific conferences. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12610000805077. PMID- 26838999 TI - Responses of Soil Bacterial Communities to Nitrogen Deposition and Precipitation Increment Are Closely Linked with Aboveground Community Variation. AB - It has been predicted that precipitation and atmospheric nitrogen (N) deposition will increase in northern China; yet, ecosystem responses to the interactive effects of water and N remain largely unknown. In particular, responses of belowground microbial community to projected global change and their potential linkages to aboveground macro-organisms are rarely studied. In this study, we examined the responses of soil bacterial diversity and community composition to increased precipitation and multi-level N deposition in a temperate steppe in Inner Mongolia, China, and explored the diversity linkages between aboveground and belowground communities. It was observed that N addition caused the significant decrease in bacterial alpha-diversity and dramatic changes in community composition. In addition, we documented strong correlations of alpha- and beta-diversity between plant and bacterial communities in response to N addition. It was found that N enriched the so-called copiotrophic bacteria, but reduced the oligotrophic groups, primarily by increasing the soil inorganic N content and carbon availability and decreasing soil pH. We still highlighted that increased precipitation tended to alleviate the effects of N on bacterial diversity and dampen the plant-microbe connections induced by N. The counteractive effects of N addition and increased precipitation imply that even though the ecosystem diversity and function are predicted to be negatively affected by N deposition in the coming decades; the combination with increased precipitation may partially offset this detrimental effect. PMID- 26839001 TI - Hepatic Artery Pseudoaneurysm After Liver Transplantation. PMID- 26839000 TI - Proteome Dynamics: Tissue Variation in the Kinetics of Proteostasis in Intact Animals. AB - Understanding the role of protein turnover in the maintenance of proteostasis requires accurate measurements of the rates of replacement of proteins in complex systems, such as intact animals. Moreover, any investigation of allometric scaling of protein turnover is likely to include species for which fully annotated proteomes are not available. We have used dietary administration of stable isotope labeled lysine to assess protein turnover rates for proteins from four tissues in the bank vole,Myodes glareolus The annotated genome for this species is not available, so protein identification was attained through cross species matching to the mouse. For proteins for which confident identifications were derived, the pattern of lysine incorporation over 40 days was used to define the rate of synthesis of individual proteins in the four tissues. The data were heavily filtered to retain a very high quality dataset of turnover rates for 1088 proteins. Comparative analysis of the four tissues revealed different median rates of degradation (kidney: 0.099 days(-1); liver 0.136 days(-1); heart, 0.054 days(-1), and skeletal muscle, 0.035 days(-1)). These data were compared with protein degradation rates from other studies on intact animals or from cells in culture and indicate that both cell type and analytical methodology may contribute to variance in turnover data between different studies. These differences were not only due to tissue-specific proteins but were reflected in gene products common to all tissues. All data are available via ProteomeXchange with identifier PXD002054. PMID- 26839002 TI - Genome-wide identification, classification, and analysis of NADP-ME family members from 12 crucifer species. AB - NADP-dependent malic enzymes (NADP-MEs) play essential roles in both normal development and stress responses in plants. Here, genome-wide analysis was performed to identify 65 putative NADP-ME genes from 12 crucifer species. These NADP-ME genes were grouped into five categories of syntenic orthologous genes and were divided into three clades of a phylogenic tree. Promoter motif analysis showed that NADP-ME1 genes in Group IV were more conserved with each other than the other NADP-ME genes in Groups I and II. A nucleotide motif involved in ABA responses, desiccation and seed development was found in the promoters of most NADP-ME1 genes. Generally, the NADP-ME genes of Brassica rapa, B. oleracea and B. napus had less introns than their corresponding Arabidopsis orthologs. In these three Brassica species, the NADP-ME genes derived from the least fractionated subgenome have lost less introns than those from the medium fractionated and most fractionated subgenomes. BrNADP-ME1 showed the highest expression in petals and mature embryos. Two paralogous NADP-ME2 genes (BrNADP-ME2a and BrNADP-ME2b) shared similar expression profiles and differential expression levels. BrNADP-ME3 showed down-regulation during embryogenesis and reached its lowest expression in early cotyledonary embryos. BrNADP-ME4 was expressed widely in multiple organs and showed high expression during the whole embryogenesis process. Different NADP ME genes of B. rapa showed differential gene expression profiles in young leaves after ABA treatment or cold stress. Our genome-wide identification and characterization of NADP-ME genes extend our understanding of the evolution or function of this family in Brassicaceae. PMID- 26839004 TI - Reducing central serotonin in adulthood promotes hippocampal neurogenesis. AB - Chronic administration of selective serotonin reuptake inhibitors (SSRIs), which up-regulates central serotonin (5-HT) system function, enhances adult hippocampal neurogenesis. However, the relationship between central 5-HT system and adult neurogenesis has not fully been understood. Here, we report that lowering 5-HT level in adulthood is also able to enhance adult hippocampal neurogenesis. We used tamoxifen (TM)-induced Cre in Pet1-CreER(T2) mice to either deplete central serotonergic (5-HTergic) neurons or inactivate 5-HT synthesis in adulthood and explore the role of central 5-HT in adult hippocampal neurogenesis. A dramatic increase in hippocampal neurogenesis is present in these two central 5-HT deficient mice and it is largely prevented by administration of agonist for 5 HTR2c receptor. In addition, the survival of new-born neurons in the hippocampus is enhanced. Furthermore, the adult 5-HT-deficient mice showed reduced depression like behaviors but enhanced contextual fear memory. These findings demonstrate that lowering central 5-HT function in adulthood can also enhance adult hippocampal neurogenesis, thus revealing a new aspect of central 5-HT in regulating adult neurogenesis. PMID- 26839006 TI - Comment: Management of De Novo Chronic Myelogenous Leukemia and Imatinib-Induced Acute Rhabdomyolysis With the Second-Generation Tyrosine Kinase Inhibitor Dasatinib. PMID- 26839003 TI - Gametocyte clearance dynamics following oral artesunate treatment of uncomplicated falciparum malaria in Malian children. AB - Artemisinin-based combination therapies decrease Plasmodium gametocyte carriage. However, the role of artesunate in monotherapy in vivo, the mechanisms involved, and the utility of gametocyte carriage as a potential tool for the surveillance of antimalarial resistance are poorly understood. In 2010-2011, we conducted an open-label, prospective efficacy study of artesunate as monotherapy in children 1 10 years of age with uncomplicated falciparum malaria in Bougoula-Hameau, Mali. Standard oral doses of artesunate were administered for 7 days and patients were followed up for 28 days. The data were compared to a similar study conducted in 2002-2004. Of 100 children enrolled in the 2010-2011 study, 92 were analyzed and compared to 217 children enrolled in the 2002-2004 study. The proportion of gametocyte carriers was unchanged at the end of treatment (23% at baseline vs. 24% on day 7, p = 1.0) and did not significantly decline until day 21 of follow up (23% vs. 6%, p = 0.003). The mean gametocyte density at inclusion remained unchanged at the end of treatment (12 gametocytes/MUL vs. 16 gametocytes/MUL, p = 0.6). Overall, 46% of the 71 initial non-carriers had gametocytes detected by day 7. Similar results were found in the 2002-2004 study. In both studies, although gametocyte carriage significantly decreased by the end of the 28-day follow-up, artesunate did not clear mature gametocytes during treatment and did not prevent the appearance of new stage V gametocytes as assessed by light microscopy. Baseline gametocyte carriage was significantly higher 6 years after the deployment of artemisinin-based combination therapies in this setting. PMID- 26839005 TI - Reply: Adverse Drug Reactions in Pediatric Emergency Medicine. PMID- 26839007 TI - Effects of high and low 17beta-estradiol doses on focal cerebral ischemia in rats. AB - The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17beta-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n = 40 per group) were randomized into three groups, subcutaneously administered different doses of 17beta-estradiol and subjected to transient middle cerebral artery occlusion. The modified sticky tape test was performed after 24 h and the rats were subsequently sacrificed for infarct size measurements. In contrast to our hypothesis, a significant negative correlation between 17beta-estradiol dose and infarct size was found (p = 0.018). Thus, no support was found for the hypothesis that 17beta-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the findings indicate that the higher the dose of 17beta-estradiol, the smaller the infarct. PMID- 26839008 TI - Peculiar liquid-feeding and pathogen transmission behavior of Aedes togoi and comparison with Anopheles sinensis. AB - Female mosquitoes transmit various diseases as vectors during liquid-feeding. Identifying the determinants of vector efficiency is a major scientific challenge in establishing strategies against these diseases. Infection rate and transmission efficiency are interconnected with the mosquito-induced liquid feeding flow as main indexes of vector efficiency. However, the relationship between liquid-feeding characteristics and pathogen remains poorly understood. The liquid-feeding behavior of Aedes togoi and Anopheles sinensis was comparatively investigated in conjunction with vector efficiency via micro particle image velocimetry. The flow rates and ratio of the ejection volume of Aedes togoi were markedly higher than those of Anophels sinensis. These differences would influence pathogen re-ingestion. Wall shear stresses of these mosquito species were also clearly discriminatory affecting the infective rates of vector-borne diseases. The variations in volume of two pump chambers and diameter of proboscis of these mosquito species were compared to determine the differences in the liquid-feeding process. Liquid-feeding characteristics influence vector efficiency; hence, this study can elucidate the vector efficiency of mosquitoes and the vector-pathogen interactions and contribute to the development of strategies against vector-borne diseases. PMID- 26839009 TI - Validation of two US risk scores for percutaneous coronary intervention in a single-center Portuguese population of patients with acute coronary syndrome. AB - INTRODUCTION: New scores have been developed and validated in the US for in hospital mortality risk stratification in patients undergoing coronary angioplasty: the National Cardiovascular Data Registry (NCDR) risk score and the Mayo Clinic Risk Score (MCRS). We sought to validate these scores in a European population with acute coronary syndrome (ACS) and to compare their predictive accuracy with that of the GRACE risk score. METHODS: In a single-center ACS registry of patients undergoing coronary angioplasty, we used the area under the receiver operating characteristic curve (AUC), a graphical representation of observed vs. expected mortality, and net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analysis to compare the scores. RESULTS: A total of 2148 consecutive patients were included, mean age 63 years (SD 13), 74% male and 71% with ST-segment elevation ACS. In-hospital mortality was 4.5%. The GRACE score showed the best AUC (0.94, 95% CI 0.91-0.96) compared with NCDR (0.87, 95% CI 0.83-0.91, p=0.0003) and MCRS (0.85, 95% CI 0.81-0.90, p=0.0003). In model calibration analysis, GRACE showed the best predictive power. With GRACE, patients were more often correctly classified than with MCRS (NRI 78.7, 95% CI 59.6-97.7; IDI 0.136, 95% CI 0.073-0.199) or NCDR (NRI 79.2, 95% CI 60.2-98.2; IDI 0.148, 95% CI 0.087-0.209). CONCLUSION: The NCDR and Mayo Clinic risk scores are useful for risk stratification of in-hospital mortality in a European population of patients with ACS undergoing coronary angioplasty. However, the GRACE score is still to be preferred. PMID- 26839010 TI - Efficacy and safety of the Chaihuguizhiganjiang-suanzaoren granule on primary insomnia: study protocol for a randomised controlled trial. AB - INTRODUCTION: Insomnia is a highly prevalent, often debilitating and economically burdensome sleep disorder with limited effective therapies. Few data are available to understand which of the therapeutic alternatives is the most effective for patients with insomnia, especially for Traditional Chinese Medicine (TCM). Chinese herbal medicine, as a typical TCM, is one of the most popular complementary and alternative therapies for insomnia. We aim to evaluate the efficacy and safety of the Chaihuguizhiganjiang-suanzaoren granule (CSG), a Chinese herbal medicine treatment, in patients with primary insomnia. METHODS AND ANALYSIS: This is a multicentre, placebo-controlled, double-blinded, randomised controlled clinical trial. A total of 258 participants are randomly allocated to two groups: the intervention group or the placebo group. The intervention group receives CSG and the placebo group receives a placebo granule. The patients receive either CSG or placebo two times daily for 8 weeks. The primary outcome is the Pittsburgh sleep quality index (PSQI). Secondary outcomes include the Insomnia Severity Index (ISI), Total Sleep Time (TST) and the Short-Form Health Survey (SF-36). The assessment is performed at baseline (before randomisation), 4, 8 and 12 weeks after randomisation. ETHICS AND DISSEMINATION: The protocol has been approved by the Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University (reference: 2014BL-003-01). The trial will be helpful in identifying the efficacy and safety of CSG in patients with primary insomnia. TRIAL REGISTRATION NUMBER: ISRCTN22001145; Pre-results. PMID- 26839011 TI - Evaluation of the feasibility and acceptability of the 'Care for Stroke' intervention in India, a smartphone-enabled, carer-supported, educational intervention for management of disability following stroke. AB - OBJECTIVES: (1) To identify operational issues encountered by study participants in using the 'Care for Stroke' intervention; (2) to evaluate the feasibility and acceptability of the intervention. DESIGN: Mixed-methods research design. SETTING: Participant's home. Participants were selected from a tertiary hospital in Chennai, South India. PARTICIPANTS: Sixty stroke survivors treated and discharged from the hospital, and their caregivers. INTERVENTION: 'Care for Stroke' is a smartphone-enabled, educational intervention for management of physical disabilities following stroke. It is delivered through a web-based, smartphone-enabled application. It includes inputs from stroke rehabilitation experts in a digitised format. METHODS: Evaluation of the intervention was completed in two phases. In the first phase, the preliminary intervention was field-tested with 30 stroke survivors for 2 weeks. In the second phase, the finalised intervention was provided to a further 30 stroke survivors to be used in their homes with support from their carers for 4 weeks. PRIMARY AND SECONDARY OUTCOME MEASURES: PRIMARY OUTCOMES: (1) operational difficulties in using the intervention; (2) feasibility and acceptability of the intervention in an Indian setting. Disability and dependency were assessed as secondary outcomes. RESULTS: Field-testing identified operational difficulties related to connectivity, video streaming, picture clarity, quality of videos, and functionality of the application. The intervention was reviewed, revised and finalised before pilot testing. Findings from the pilot-testing showed that the 'Care for Stroke' intervention was feasible and acceptable. Over 90% (n=27) of the study participants felt that the intervention was relevant, comprehensible and useful. Over 96% (n=29) of the stroke survivors and all the caregivers (100%, n=30) rated the intervention as excellent and very useful. These findings were supported by qualitative interviews. CONCLUSIONS: Evaluation indicated that the 'Care for Stroke' intervention was feasible and acceptable in an Indian context. An assessment of effectiveness is now warranted. PMID- 26839012 TI - Cross-sectional study on parental pro-drinking practices and adolescent alcohol drinking in Hong Kong. AB - OBJECTIVES: To investigate the association between parental pro-drinking practices (PPDPs) and alcohol drinking in Hong Kong Chinese adolescents. DESIGN: A cross-sectional study. SETTING: 4 randomly selected secondary schools in Hong Kong. PARTICIPANTS: 1738 students (mean age 14.6 years +/- 2.0, boys 67.8%). MAIN OUTCOME MEASURES: Drinking status, drinking intention and exposure to 9 PPDPs (eg, seeing parents drunk, helping parents buy alcohol, encouraged to drink by parents) were reported by students. Logistic regression was used to compute adjusted ORs (AORs) of drinking and intention to drink by each PPDP and the number of PPDPs (0, 1-2, 3-4, 5 or above), adjusting for sociodemographic characteristics, parental drinking and school clustering. RESULTS: Nearly half (48.6%) of the students were ever-drinkers, 16.2% drank monthly (at least once per month) and 40.3% intended to drink in the next 12 months. Most PPDPs were significantly associated with ever drinking (AORs 1.40-6.20), monthly drinking (AORs 1.12-8.20) and intention to drink (AORs 1.40-5.02). Both ever and monthly drinking were most strongly associated with parental training of drinking capacity (ability to drink more without getting drunk) with AORs of 6.20 and 8.20 (both p<0.001), respectively. Adolescent drinking intention was most strongly associated with parental encouragement of drinking and training of drinking capacity with AORs of 3.19 and 5.02 (both p<0.001), respectively. CONCLUSIONS: Exposure to PPDPs was associated with ever drinking, monthly drinking and drinking intention in Hong Kong Chinese adolescents. More studies, especially prospective studies, should be conducted to confirm these results, followed by interventional studies. PMID- 26839013 TI - Does preoperative rehabilitation for patients planning to undergo joint replacement surgery improve outcomes? A systematic review and meta-analysis of randomised controlled trials. AB - OBJECTIVES: The clinical impact of preoperative physiotherapy on recovery after joint replacement remains controversial. This systematic review aimed to assess the clinical impact of prehabilitation before joint replacement. DESIGN: We searched PubMed, Embase and Cochrane CENTRAL up to November 2015 for randomised controlled trials comparing prehabilitation versus no prehabilitation before joint replacement surgery. Postoperative pain and function scores were converted to Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function subscales (0-100, high scores indicate worse outcome). Random effects meta-analysis was performed to calculate weighted mean differences (WMD, 95% CI), subgrouped by hip and knee surgery. PRIMARY AND SECONDARY OUTCOMES: Postoperative pain and function scores, time to resume activities of daily living, quality of life, length of hospital stay, total cost, patient satisfaction, postoperative complications, any adverse events and discontinuations. RESULTS: Of 22 studies (1492 patients), 18 had high risk of bias. Prehabilitation slightly reduced pain scores within 4 weeks postoperatively (WMD -6.1 points, 95% CI -10.6 to -1.6 points, on a scale of 0-100), but differences did not remain beyond 4 weeks. Prehabilitation slightly improved WOMAC function score at 6-8 and 12 weeks (WMD -4.0, 95% CI -7.5 to -0.5), and time to climbing stairs (WMD -1.4 days, 95% CI -1.9 to -0.8 days), toilet use ( 0.9 days, 95% CI -1.3 to -0.5 days) and chair use (WMD -1.2 days, 95% CI -1.7 to 0.8 days). Effects were similar for knee and hip surgery. Differences were not found for SF-36 scores, length of stay and total cost. Other outcomes of interest were inadequately reported. CONCLUSIONS: Existing evidence suggests that prehabilitation may slightly improve early postoperative pain and function among patients undergoing joint replacement; however, effects remain too small and short-term to be considered clinically-important, and did not affect key outcomes of interest (ie, length of stay, quality of life, costs). PMID- 26839014 TI - 'Much clearer with pictures': using community-based participatory research to design and test a Picture Option Grid for underserved patients with breast cancer. AB - OBJECTIVE: Women of low socioeconomic status (SES) diagnosed with early stage breast cancer experience decision-making, treatment and outcome disparities. Evidence suggests that decision aids can benefit underserved patients, when tailored to their needs. Our aim was to develop and test the usability, acceptability and accessibility of a pictorial encounter decision aid targeted at women of low SES diagnosed with early stage breast cancer. DESIGN: Community based participatory research (CBPR) using think-aloud protocols (phases 1 and 2) and semistructured interviews (phase 3). SETTING: Underserved community settings (eg, knitting groups, bingo halls, senior centres) and breast clinics. PARTICIPANTS: In phase 1, we recruited a convenience sample of clinicians and academics. In phase 2, we targeted women over 40 years of age, of low SES, regardless of breast cancer history, and in phase 3, women of low SES, recently diagnosed with breast cancer. INTERVENTION: The pictorial encounter decision aid was derived from an evidence-based table comparing treatment options for breast cancer (http://www.optiongrid.org). OUTCOME MEASURES: We assessed the usability, acceptability and accessibility of the pictorial decision aid prototypes using the think-aloud protocol and semistructured interviews. RESULTS: After initial testing of the first prototype with 18 academics and health professionals, new versions were developed and tested with 53 lay individuals in community settings. Usability was high. In response to feedback indicating that the use of cartoon characters was considered insensitive, a picture-only version was developed and tested with 23 lay people in phase 2, and 10 target users in phase 3. CONCLUSIONS AND RELEVANCE: Using CBPR methods and iterative user testing cycles improved usability and accessibility, and led to the development of the Picture Option Grid, entirely guided by multiple stakeholder feedback. All women of low SES recently diagnosed with early stage breast cancer found the Picture Option Grid usable, acceptable and accessible. PMID- 26839015 TI - Medication-related burden and patients' lived experience with medicine: a systematic review and metasynthesis of qualitative studies. AB - OBJECTIVE: To explore medication-related burden (MRB) and patients' lived experience with medicines (PLEM) without regard to particular medication therapies or medical conditions. DESIGN: Systematic review and metasynthesis of qualitative studies. DATA SOURCES: MEDLINE, EMBASE, International Pharmaceutical Abstracts, PsycINFO, Global health, CINAHL and Web of Science were searched from January 2000 to August 2014 using medication burden and patients' lived experience terms. SYNTHESIS METHODS: Synthesis was undertaken following metaethnography methods and a comparative thematic analysis technique. RESULTS: 34 articles from 12 countries with a total of 1144 participants were included. 3 major inter-related themes emerged central to PLEM: MRB, medication related beliefs and medication taking practice. The negative impact of MRB, due to its interference on patients' daily lives and effects on well-being, its influence on patients' beliefs and behaviours, and a potential risk for drug-related problems (DRPs) was evident. This resulted in non-adherence and poorer outcomes (unachieved therapeutic goals and damage to patients' health). Patients who experienced MRB interference in their life over time begin to juggle their medicines. Others continue their medicines despite experiencing MRB resulting in compromised physical, social or psychological well-being. CONCLUSIONS: There is a shared commonality of PLEM among the studies. MRB plays a central role in influencing patients' health and well-being, beliefs and behaviour towards medicines. Given the complexity of MRB and its impact evident from this review, there is a need for healthcare practitioners to have insight into PLEM in therapeutic care plans. Understanding PLEM is an opportunity for practitioners to identify particular MRBs that patients encounter, and provide individualised care through selection of therapeutic care plans that suit a patient's life. This may assist in helping to achieve patients' medication-related needs, and improve medication therapy and health outcomes. PMID- 26839017 TI - A cell-centered, agent-based framework that enables flexible environment granularities. AB - BACKGROUND: Mechanistic explanations of cell-level phenomena typically adopt an observer perspective. Explanations developed from a cell's perspective may offer new insights. Agent-based models lend themselves to model from an individual perspective, and existing agent-based models generally utilize a regular lattice based environment. A framework which utilizes a cell's perspective in an off lattice environment could improve the overall understanding of biological phenomena. RESULTS: We present an agent-based, discrete event framework, with a demonstrative focus on biomimetic agents. The framework was first developed in 2 dimensions and then extended, with a subset of behaviors, to 3-dimensions. The framework is expected to facilitate studies of more complex biological phenomena through exploitation of a dynamic Delaunay and Voronoi off-lattice environment. We used the framework to model biological cells and to specifically demonstrate basic biological cell behaviors in two- and three-dimensional space. Potential use cases are highlighted, suggesting the utility of the framework in various scenarios. CONCLUSIONS: The framework presented in this manuscript expands on existing cell- and agent-centered methods by offering a new perspective in an off lattice environment. As the demand for biomimetic models grows, the demand for new methods, such as the presented Delaunay and Voronoi framework, is expected to increase. PMID- 26839019 TI - Somatostatin receptors imaging and therapy in a patient affected by esthesioneuroblastoma with meningeal metastases. A classic example of theranostic approach. PMID- 26839018 TI - Genetic risk variants in the CDKN2A/B, RTEL1 and EGFR genes are associated with somatic biomarkers in glioma. AB - During the last years, genome wide association studies have discovered common germline genetic variants associated with specific glioma subtypes. We aimed to study the association between these germline risk variants and tumor phenotypes, including copy number aberrations and protein expression. A total of 91 glioma patients were included. Thirteen well known genetic risk variants in TERT, EGFR, CCDC26, CDKN2A, CDKN2B, PHLDB1, TP53, and RTEL1 were selected for investigation of possible correlations with the glioma somatic markers: EGFR amplification, 1p/19q codeletion and protein expression of p53, Ki-67, and mutated IDH1. The CDKN2A/B risk variant, rs4977756, and the CDKN2B risk variant, rs1412829 were inversely associated (p = 0.049 and p = 0.002, respectively) with absence of a mutated IDH1, i.e., the majority of patients homozygous for the risk allele showed no or low expression of mutated IDH1. The RTEL1 risk variant, rs6010620 was associated (p = 0.013) with not having 1p/19q codeletion, i.e., the majority of patients homozygous for the risk allele did not show 1p/19q codeletion. In addition, the EGFR risk variant rs17172430 and the CDKN2B risk variant rs1412829, both showed a trend for association (p = 0.055 and p = 0.051, respectively) with increased EGFR copy number, i.e., the majority of patients homozygote for the risk alleles showed chromosomal gain or amplification of EGFR. Our findings indicate that CDKN2A/B risk genotypes are associated with primary glioblastoma without IDH mutation, and that there is an inverse association between RTEL1 risk genotypes and 1p/19q codeletion, suggesting that these genetic variants have a molecular impact on the genesis of high graded brain tumors. Further experimental studies are needed to delineate the functional mechanism of the association between genotype and somatic genetic aberrations. PMID- 26839020 TI - "Comet tail sign": A pitfall of post-gadolinium magnetic resonance imaging findings for metastatic brain tumors. AB - A highly enhanced cap attached to the surface of metastatic tumors in the brain parenchyma is occasionally encountered on magnetic resonance (MR) images. This atypical enhanced cap tends to occur in severe peritumoral edema and may produce the characteristic bulge of a metastatic mass lesion termed the "comet tail sign" (CTS). The purpose of this study was to demonstrate the features of the CTS using MR imaging and pathological findings, and to clarify its clinical relevance. We selected 21 consecutive cases of newly diagnosed metastases from MR imaging studies that demonstrated the CTS; all had diffuse peritumoral edema. The MR T2 weighted images showed similarly homogenous and high intensity signals in both the tail and peritumoral edema. Fourteen of the 21 patients underwent surgical resection of their tumors, and 12 tails were separately removed for pathological examination, no tumor cells which revealed. We speculate that the CTS does not contain neoplastic tissues but is observed as a result of the leakage of contrast medium from the tumor body into the interstitial space of the white matter. Although CTS is a peculiar and uncommon enhancement pattern, it has clinical significance in determining the extent of the margin for invasive local treatments, such as surgical resection or stereotactic radiotherapy; this is particularly true in and near the eloquent areas. PMID- 26839022 TI - Long persistent phosphors--from fundamentals to applications. AB - Owing to the unique mechanism of photoelectron storage and release, long persistent phosphorescence, also called long persistent luminescence or long lasting afterglow/phosphorescence, plays a pivotal role in the areas of spectroscopy, photochemistry, photonics and materials science. In recent years, more research has focused on the manipulation of the morphology, operational wavebands and persistent duration of long persistent phosphors (LPPs). These desired achievements stimulated the growing interest in designing bio-labels, photocatalysts, optical sensors, detectors and photonic devices. In this review, we present multidisciplinary research on synthetic methods, afterglow mechanisms, characterization techniques, materials system, and applications of LPPs. First, we introduce the recent developments in LPPs for the synthesis of nanoparticles from the aspects of particle sizes, monodispersity and homogeneity based on the urgent application of bio-imaging. In the later sections, we present the possible mechanisms, which involve the variation of trap distribution during the trapping and de-trapping process, complicated photo-ionization reaction of trap site levels and impurity centers together with their corresponding migration kinetics of carriers. Meanwhile, we emphasize the characterization techniques of defects, used to qualitatively or quantitatively describe the types, concentrations and depths of the traps. This review article also highlights the recent advances in suggested LPPs materials with a focus on the LPPs' hosts and optically active centers as well as their control, tuning and intrinsic links. We further discuss the classification of LPPs based on the different emission and excitation wavebands from the ultraviolet to the near-infrared region along with an overview of the activation mode of afterglow. Afterwards, we provide an exhibition of new products towards diverse application fields, including solar energy utilization, bio-imaging, diagnosis, and photocatalysts. Finally, we summarize the current achievements, discuss the problems and provide suggestions for potential future directions in the aforementioned parts. PMID- 26839021 TI - The evolving role of enzalutamide on the treatment of prostate cancer. AB - The field of prostate cancer has witnessed incredible progress in the last decade, owing to the approval of multiple survival-prolonging treatments for metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide is a nonsteroidal androgen receptor inhibitor that targets multiple steps in the androgen receptor signaling axis. It has been approved for the treatment of mCRPC both in the postdocetaxel and in the chemotherapy-naive settings. We summarize the milestones in the development of enzalutamide in patients with prostate cancer. Special focus is placed on the results of the STRIVE Phase II clinical trial comparing head to head enzalutamide and bicalutamide in patients with nonmetastatic and mCRPC who have failed androgen deprivation and in other ongoing trials in the same setting and in earlier disease phases. PMID- 26839023 TI - Efficacy of methylnaltrexone for the treatment of opiod-induced constipation: a meta-analysis and systematic review. AB - OBJECTIVE: Constipation is a common adverse effect in patients requiring long term opioid therapy for pain control. Methylnaltrexone, a quaternary peripheral mu-opioid receptor antagonist, is an effective treatment of opioid induced constipation (OIC) without affecting centrally mediated analgesia. Our objective was to conduct a review and meta-analysis to evaluate the efficacy of methylnaltrexone for treatment of OIC, as well as to provide a clinical discussion regarding newly developed alternatives and provide the current treatment algorithm utilized at our institution. METHODS: We performed a systematic review and meta-analysis of randomized control trials using Cochrane Collaboration Databases and MEDLINE from 2007-present. Literature related to methylnaltrexone, opioids, opioid receptors, opioid antagonists, opioid-induced constipation were reviewed. A meta-analysis was completed with the primary outcome of rescue-free bowel movement (RFBM) within four hours of administration. All pooled analyses were based on random-effects models. RESULTS: 1239 patients were analyzed; 599 received methylnaltrexone and 640 received placebo. With a 95% CI calculated, the true risk difference is between 0.267 and 0.385, demonstrating a statistically significant difference in RFBM between treatment and placebo groups (p < 0.0001). Both the 0.15 mg/kg, 0.30 mg/kg doses every other day, and 12 mg/day dose were found to have increased risk of RFBM compared to placebo. CONCLUSION: Results support the use of methylnaltrexone. Furthermore, the use of methylnaltrexone to induce laxation may decrease use of health care resources, increase work productivity, and improve cost utilization. New treatments have been made available; however, controlled clinical studies are needed to demonstrate long-term efficacy, safety and cost-effectiveness. Possible limitations of this study include the relatively small number of randomized, placebo-controlled trials investigating the efficacy of methylnaltrexone versus placebo. There is also the possibility of publication bias, which may lead to overestimating the efficacy of methylnaltrexone in treating OIC. PMID- 26839025 TI - Bronchioloalveolar Carcinoma and Minimally Invasive Adenocarcinoma. AB - The most recent WHO classification of lung cancer defines bronchioloalveolar carcinoma (BAC) as a noninvasive carcinoma or adenocarcinoma in situ. However, the use of this terminology is not uniform and does not reflect standardized criteria. As a result, the diagnosis of BAC has been used in association with small, solitary, and well-differentiated adenocarcinoma as well as tumors with advanced clinical stage. At present, there is a growing consensus among specialists in thoracic oncology that BAC or adenocarcinoma in situ is a rare tumor, and the term should be restricted to adenocarcinomas that show a pure lepidic pattern of growth. The amount of invasive component present in a tumor with a predominant lepidic growth pattern has also been under intense scrutiny. The concept of minimally invasive adenocarcinoma is developing in order to differentiate a pure BAC from an invasive adenocarcinoma that still carries an excellent prognosis. PMID- 26839024 TI - MALDI-TOF MS based carbapenemase detection from culture isolates and from positive blood culture vials. AB - BACKGROUND: Antibiotic resistance in bacteria leads to massive health problems. Incidence of carbapenem and multidrug resistance in Gram-negative bacteria are increasing globally and turn out to be a very urgent challenge in health care. Resistant bacteria play an important clinical role during hospital outbreaks as well as in sepsis. Rapid diagnostic tests are necessary to provide immediate information for antimicrobial treatment and infection control measures. METHODS: Our mass spectrometry-based assay was validated with 63 carbapenemase-producing Gram-negative bacterial isolates, and 35 carbapenem-resistant Gram-negative species with no carbapenemase production. These were analyzed from solid culture media and positive blood culture vials. After 4 h of incubation the carbapenemase products were analyzed with the MALDI-TOF MS. All the isolates were genotyped for carbapenemase genes by PCR and sequencing. RESULTS: For culture isolates the concordance of hydrolysis assay to genetic results was 98 % for OXA variants, KPC, VIM, IMP, GIM, and NDM. In contrast, only 14 of 29 Acinetobacter baumannii isolates carrying the OXA and NDM genes could be identified from blood culture. However, from blood culture vials our method allowed the detection of carbapenemases in 98 % of Pseudomonas and Enterobacteriaceae isolates harboring different genes. CONCLUSIONS: This MALDI-TOF MS-based assay permitted the detection of carbapenemases either from solid culture media (98-100 %) or blood culture vials (96 %) for all non-A. baumannii isolates within 4 h. In case of A. baumannii isolates the assay was highly sensitive for the detection of carbapenemases directly from solid culture media. PMID- 26839026 TI - Pulmonary Neuroendocrine Tumors. AB - Pulmonary neuroendocrine tumors are frequently encountered as small biopsy and resection specimens. Although the World Health Organization (WHO) classification is used as a diagnostic framework globally and in daily practice, it is not without controversy and practical difficulties. The WHO criteria for pulmonary neuroendocrine tumors are reviewed with the recognition that the definitions are based on resected specimens, which are often not the usual clinical circumstances. A practical approach is emphasized, and the differential diagnosis is discussed with particular attention to the context in which diagnostic difficulties are most frequently encountered, such as small biopsies and frozen sections. PMID- 26839027 TI - Lung Carcinoma Staging Problems. AB - The tumor-node-metastasis (TNM) system is the most commonly used staging system for cancers, including lung cancer. The TNM descriptors and the stage groupings reflect differences in patient prognosis and choices for specific therapies. Generally, the higher the T, N, or M, and the higher the stage grouping, the worse the prognosis is for patients in that category. TNM stage is traditionally the most important factor predicting survival of lung cancer patients. PMID- 26839028 TI - Benign and Malignant Mesothelial Proliferation. AB - Malignant mesothelioma (MM) is a rare primary malignant tumor of the surface serosal cells. The diagnosis of MM is challenging with a broad differential diagnosis. For many decades, studies have focused on distinguishing MM from other types of cancer; however, benign mesothelial cell hyperplasia, especially in small biopsies, has emerged as a major problem. The features of pleural lesions are somewhat different from peritoneal diseases, and this article primarily focuses on pleural diseases. Thorough interpretation and correlation of clinical, radiologic, and pathologic findings are essential for a correct diagnosis. PMID- 26839029 TI - Asbestos-Related Lung Disease. AB - Asbestos is a high-profile health hazard. This article examines the assessment asbestos-related malignant mesothelioma and lung cancer. The risk of developing these diseases increases in proportion to the cumulative dose. As persons with heavy occupational asbestos exposures are diminishing, the observed latent period for asbestos-related disease extends making the assessment of an individual's cumulative dose is now more problematic. PMID- 26839030 TI - A Practical Approach to the Evaluation of Lymphoid and Plasma Cell Infiltrates in the Lung. AB - Pulmonary biopsy specimens demonstrate varying degrees of infiltration by lymphoid cells and plasma cells, which may raise concern about involvement of a lymphoid or plasma cell neoplasm. Although paraffin section immunohistochemical stains and molecular genotyping studies are capable of assisting in the distinction between reactive and neoplastic infiltrates, it can be difficult to decide what studies to perform. This article describes a practical approach for the evaluation of lymphoid and plasma cell infiltrates in the lung through the identification of several key histologic features. PMID- 26839031 TI - Vasculitis. AB - Vasculitic syndromes involving the lung present a unique challenge for pathologists because of the histologic overlap with other disorders and the clinical implications of the diagnosis in regard to clinical management. This article reviews the more common vasculitic syndromes involving the lung, concentrating primarily on Wegener granulomatosis, Churg-Strauss syndrome, necrotizing sarcoid, microscopic polyangiitis, and diffuse alveolar hemorrhage syndromes. The article focuses on a review of the recent literature, diagnostic approach, and differential diagnosis. PMID- 26839032 TI - Small Airways Disease. AB - Small airways diseases are best defined pathologically as a diverse group of conditions that primarily involve bronchioles and acartilagenous airways 2 mm or less in diameter, which include membranous bronchioles, respiratory bronchioles, and alveolar ducts. Small airways can be involved with disease primarily or secondarily. The concept of small airways disease varies among specialties, with clinicians generally considering them in terms of terminal airway changes causing airflow obstruction, radiologists considering them in the context of direct signs and indirect signs identified on high-resolution computed tomography scans, and pathologists evaluating them based entirely or almost entirely on the histologic changes present in the bronchioles, with or without associated changes involving bronchi and alveoli. The histologic features of small airways diseases may be confusing because they overlap. There may be incomplete assessment of the histologic process with limited biopsy. Other disease processes may occur along with a small airways disease, and may obscure or confound its histologic features. This article focuses on the histologic changes diagnostic of a variety of primary and secondary small airways diseases. Because the histologic features involve bronchioles, gross findings are often minimal and/or nonspecific. The article provides a nonexhaustive examination of conditions and diseases involving the small airways, focusing on the microscopic features, with emphasis on the limitations of histologic diagnosis and differential diagnosis. PMID- 26839033 TI - Hypersensitivity Pneumonitis: Essential Radiologic and Pathologic Findings. AB - Hypersensitivity pneumonitis is a diffuse, granulomatous interstitial lung disease caused by repeated exposure to a wide spectrum of environmental antigens. Clinical, radiologic, and histologic findings are quite variable and mimic many other diseases; therefore, diagnosis depends on a constellation of findings rather than a single defining feature. High-resolution computed tomography (HRCT) plays a critical role in this setting. The presence of centrilobular nodules, multifocal ground glass opacities, and evidence of air trapping in the expiratory phase of respiration is highly suggestive of hypersensitivity pneumonitis and can direct clinicians to the correct diagnosis. For the pathologist, typical HRCT findings not only corroborate the diagnosis of hypersensitivity pneumonitis when the characteristic triad of airway-centered chronic interstitial inflammation, interstitial poorly formed non-necrotizing granulomas, and organizing pneumonia is present on biopsy, but also improve diagnostic confidence in biopsies lacking components of the diagnostic histologic triad. Importantly, the presence of focal or unilateral imaging findings should prompt a careful search by the pathologist for an infectious etiology, thus avoiding errors in determining the significance of granulomas on biopsy. This article reviews the essential radiologic and pathologic findings in hypersensitivity pneumonitis, discusses the primary considerations in the differential diagnosis, and offers an approach to biopsy evaluation. PMID- 26839034 TI - Erratum. PMID- 26839035 TI - Pulmonary Pathology Integral to Clinical Decision Making. PMID- 26839036 TI - Reconfigurable logic via gate controlled domain wall trajectory in magnetic network structure. AB - An all-magnetic logic scheme has the advantages of being non-volatile and energy efficient over the conventional transistor based logic devices. In this work, we present a reconfigurable magnetic logic device which is capable of performing all basic logic operations in a single device. The device exploits the deterministic trajectory of domain wall (DW) in ferromagnetic asymmetric branch structure for obtaining different output combinations. The programmability of the device is achieved by using a current-controlled magnetic gate, which generates a local Oersted field. The field generated at the magnetic gate influences the trajectory of the DW within the structure by exploiting its inherent transverse charge distribution. DW transformation from vortex to transverse configuration close to the output branch plays a pivotal role in governing the DW chirality and hence the output. By simply switching the current direction through the magnetic gate, two universal logic gate functionalities can be obtained in this device. Using magnetic force microscopy imaging and magnetoresistance measurements, all basic logic functionalities are demonstrated. PMID- 26839037 TI - A maternal deletion upstream of the imprint control region 2 in 11p15 causes loss of methylation and familial Beckwith-Wiedemann syndrome. AB - Beckwith-Wiedemann syndrome (BWS; OMIM #130650) is an overgrowth syndrome caused by different genetic or epigenetic alterations affecting imprinted regions on chromosome 11p15.5. Here we report a family with multiple offspring affected with BWS including giant omphalocoeles in which maternal transmission of a chromosomal rearrangement including an inversion and two deletions leads to hypomethylation of the imprint control region 2 (ICR2). As the deletion includes the promoter and 5' part of the KCNQ1 gene, we suggest that transcription of this gene may be involved in establishing the maternal methylation imprint of the ICR2, which is located in intron 10 of KCNQ1. PMID- 26839038 TI - Trans-ethnic study design approaches for fine-mapping. AB - Studies that traverse ancestrally diverse populations may increase power to detect novel loci and improve fine-mapping resolution of causal variants by leveraging linkage disequilibrium differences between ethnic groups. The inclusion of African ancestry samples may yield further improvements because of low linkage disequilibrium and high genetic heterogeneity. We investigate the fine-mapping resolution of trans-ethnic fixed-effects meta-analysis for five type II diabetes loci, under various settings of ancestral composition (European, East Asian, African), allelic heterogeneity, and causal variant minor allele frequency. In particular, three settings of ancestral composition were compared: (1) single ancestry (European), (2) moderate ancestral diversity (European and East Asian), and (3) high ancestral diversity (European, East Asian, and African). Our simulations suggest that the European/Asian and European ancestry only meta-analyses consistently attain similar fine-mapping resolution. The inclusion of African ancestry samples in the meta-analysis leads to a marked improvement in fine-mapping resolution. PMID- 26839039 TI - Redox chemistry of the molecular interactions between tea catechins and human serum proteins under simulated hyperglycemic conditions. AB - Carbonylation is an irreversible modification in oxidized proteins that has been directly related to a number of health disorders including Type 2 diabetes. Dietary antioxidants have been proposed to counteract the oxidative stress occurring under hyperglycemic conditions. An understanding of the nature and consequences of the molecular interactions between phytochemicals and human plasma proteins is of utmost scientific interest. Three tea catechins namely epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG) were tested for (i) their affinity to bind to human serum albumin (HSA) and human hemoglobin (HH) and (ii) their ability to inhibit tryptophan (Trp) depletion and for the formation of specific protein carbonyls and pentosidine in the aforementioned proteins. Both proteins (20 mg mL(-1)) were allowed to react with postprandial plasmatic concentrations of the catechins (EC: 0.7 MUM, EGC: 1.8 MUM, and EGCG: 0.7 MUM) under simulated hyperglycemic conditions (12 mM glucose/0.2 mM Fe(3+)/37 degrees C/10 days). The three catechins were able to inhibit Trp oxidation and protein carbonylation in both plasma proteins. Some anti-glycation properties were linked to their binding affinities. The molecular interactions reported in the present study may explain the alleged beneficial effects of tea catechins against the redox impairment linked to hyperglycemic conditions. PMID- 26839040 TI - Association of Remitting Seronegative Symmetrical Synovitis with Pitting Edema, Polymyalgia Rheumatica, and Adenocarcinoma of the Prostate. AB - BACKGROUND: Remitting seronegative symmetrical synovitis with pitting edema (RS3PE) is a rare condition that occurs in elderly individuals. It can present alone or in association with various rheumatic or malignant diseases. CASE REPORT: An 83-year-old man presented with anemia, hyper-sedimentation, and pitting edema of the back of the hands. The patient complained of pain and stiffness of the shoulder and hip girdles, especially in the morning. He was previously diagnosed with adenocarcinoma of the prostate. After 3 years of watchful waiting, treatment with goserelin, a gonadotropin releasing hormone agonist, was started, when PSA had increased to 67.9 ug/l. About 1 year before the cancer treatment, the patient also presented with sore and swollen hands, compatible with RS3PE, which remitted after a few months of prostatic cancer treatment. Thorough laboratory evaluation was performed upon admission to the Rheumatology Department and he was referred for FDG PET/CT on suspicion of metastases of the previously diagnosed prostatic cancer. PET/CT imaging revealed increased FDG uptake in the soft tissues around the shoulders and hips, but no evidence of bone metastasis or other malignant findings. A diagnosis of polymyalgia rheumatica (PMR) together with RS3PE syndrome was made and treatment with prednisolone 15 mg/d was started, which resulted in rapid resolution of the symptoms. CONCLUSIONS: Presence of RS3PE in relation with PMR and prostatic cancer in our patient suggests a common trigger factor. To the best of our knowledge, this is the first report of a case of RS3PE that presented twice with 2 different diagnoses in the same patient. PMID- 26839041 TI - Allelopathic Polyketides from an Endolichenic Fungus Myxotrichum SP. by Using OSMAC Strategy. AB - Three new polyketides myxotritones A-C (2-4), together with a new natural product 7,8-dihydro-7R,8S-dihydroxy-3,7-dimethyl-2-benzopyran-6-one (1) were obtained from the endolichenic fungus Myxotrichum sp. by using OMSAC (One Strain, Many Compounds) method. The planar structures of these new compounds were determined by NMR experiment and HRESIMS data, and the absolute configuration of 1 was established by X-ray diffraction, and the stereochemistry of the new compounds 2 4 were determined by same biosynthesis origin, and similar CD spectra with 1. Allelopathic test showed that compound 4 significantly retarded root elongation of Arabidopsis thaliana seed, indicating that this fungus might contribute to the defense of its host lichen. From the view of biosynthetic pathway, all four compounds 1-4 might be originated from Non-Reduced Polyketide synthase (NR-PKS). PMID- 26839043 TI - Meta-analysis of Ivabradine in Patients With Stable Coronary Artery Disease With and Without Left Ventricular Dysfunction. AB - PURPOSE: Ivabradine is a novel If-channel antagonist that controls heart rate and may be helpful in treating patients with left ventricular dysfunction (LVD) who are unable to tolerate beta-blockers or achieve a heart rate of 70 beats/min with standard therapy. Three landmark trials were used for the approval of ivabradine in the United States. These trials tested ivabradine in addition to a standard of care (including beta-blockers) in patients with stable coronary artery disease (CAD) and found modest benefit in those with established LVD unable to tolerate beta-blockers. The goal of this review was to pool data from ivabradine studies in all patients with stable CAD to compare cardiovascular and safety-related outcomes. METHODS: Three randomized, double-blind, placebo-controlled trials of ivabradine added to standard treatment (including beta-blockers) in patients with stable CAD with and without LVD were reviewed for effects on mortality, cardiovascular outcomes, and adverse events. Data were independently abstracted by 2 reviewers; the Oxford quality scoring system was used to evaluate randomization, blinding, withdrawals, and dropouts; and a Mantel-Haenszel random effects pairwise meta-analysis was used to combine data into odds ratios. FINDINGS: The initial search identified 116 trials; 3 of these trials, representing 36,524 patients with stable CAD, met inclusion criteria. According to the pooled results, ivabradine did not consistently reduce all-cause mortality (odds ratio [OR], 1.00 [95% CI, 0.91-1.11]; P = 0.98], cardiovascular death (OR, 1.02 [95% CI, 0.91-1.15]; P = 0.74), or hospitalization for worsening or new onset heart-failure in patients with stable CAD (OR, 0.94 [95% CI, 0.71-1.25]; P = 0.69). Ivabradine did not increase serious adverse drug reactions (OR, 0.99 [95% CI, 0.88-1.13]; P = 0.93) or cardiac disorders (OR, 1.03 [95% CI, 0.87 1.22]; P = 0.74). However, it was associated with drug-specific effects, including new-onset atrial fibrillation (OR, 1.35 [95% CI, 1.19-1.53]; P < 0.001], bradycardia (OR, 6.54 [95% CI, 3.30-12.9]; P < 0.001), phosphenes (OR, 7.77 [95% CI, 4.12-14.63]; P < 0.001), and blurry vision (OR, 3.07 [95% CI, 2.18 4.32]; P < 0.001). IMPLICATIONS: Unselective use of ivabradine in patients with stable CAD is not supported by evidence and can be associated with new-onset atrial fibrillation, bradycardia, and drug-related nuisance adverse events. PMID- 26839042 TI - Endothelial p110gammaPI3K Mediates Endothelial Regeneration and Vascular Repair After Inflammatory Vascular Injury. AB - BACKGROUND: The integrity of endothelial monolayer is a sine qua non for vascular homeostasis and maintenance of tissue-fluid balance. However, little is known about the signaling pathways regulating regeneration of the endothelial barrier after inflammatory vascular injury. METHODS AND RESULTS: Using genetic and pharmacological approaches, we demonstrated that endothelial regeneration selectively requires activation of p110gammaPI3K signaling, which thereby mediates the expression of the endothelial reparative transcription factor Forkhead box M1 (FoxM1). We observed that FoxM1 induction in the pulmonary vasculature was inhibited in mice treated with a p110gamma-selective inhibitor and in Pik3cg(-/-) mice after lipopolysaccharide challenge. Pik3cg(-/-) mice exhibited persistent lung inflammation induced by sepsis and sustained increase in vascular permeability. Restoration of expression of either p110gamma or FoxM1 in pulmonary endothelial cells of Pik3cg(-/-) mice restored endothelial regeneration and normalized the defective vascular repair program. We also observed diminished expression of p110gamma in pulmonary vascular endothelial cells of patients with acute respiratory distress syndrome, suggesting that impaired p110gamma-FoxM1 vascular repair signaling pathway is a critical factor in persistent leaky lung microvessels and edema formation in the disease. CONCLUSIONS: We identify p110gamma as the critical mediator of endothelial regeneration and vascular repair after sepsis-induced inflammatory injury. Thus, activation of p110gamma-FoxM1 endothelial regeneration may represent a novel strategy for the treatment of inflammatory vascular diseases. PMID- 26839046 TI - President's Annual State of the Academy Report. PMID- 26839045 TI - Early Pleistocene climate in western arid central Asia inferred from loess palaeosol sequences. AB - Arid central Asia (ACA) is one of the most arid regions in the mid-latitudes and one of the main potential dust sources for the northern hemisphere. The lack of in situ early Pleistocene loess/dust records from ACA hinders our comprehensive understanding of the spatio-temporal record of aeolian loess accumulation and long term climatic changes in Asia as a whole. Here, we report the results of sedimentological, chronological and climatic studies of early Pleistocene loess palaeosol sequences (LPS) from the northeastern Iranian Golestan Province (NIGP) in the western part of ACA. Our results reveal that: 1) Accumulation of loess on the NIGP commenced at ~2.4-1.8 Ma, making it the oldest loess known so far in western ACA; 2) the climate during the early Pleistocene in the NIGP was semi arid, but wetter, warmer, and less windy than during the late Pleistocene and present interglacial; 3) orbital-scale palaeoclimatic changes in ACA during the early Pleistoceneare in-phase with those of monsoonal Asia, a relationship which was probably related to the growth and decay of northern hemisphere ice sheets. PMID- 26839044 TI - Daclatasvir and Sofosbuvir Versus Sofosbuvir and Ribavirin in Patients with Chronic Hepatitis C Coinfected with HIV: A Matching-adjusted Indirect Comparison. AB - PURPOSE: Our aim was to compare the efficacy and tolerability of daclatasvir plus sofosbuvir (DCV+SOF) versus SOF plus ribavirin (SOF+R) in patients coinfected with HIV and hepatitis C virus (HCV). METHODS: A systematic literature review of Phase III clinical trials identified 2 trials of SOF+R-PHOTON-1 (A Phase 3, Open Label Study to Investigate the Efficacy and Safety of GS-7977 Plus Ribavirin in Chronic Genotype 1, 2 and 3 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) and PHOTON-2 (A Phase 3, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir Plus Ribavirin in Chronic Genotype 1, 2, 3 and 4 Hepatitis C Virus [HCV] and Human Immunodeficiency Virus [HIV] Co-Infected Subjects) suitable for comparison with the trial of DCV+SOF in patients coinfected with HIV and HCV-ALLY-2 (A Phase 3 Evaluation of Daclatasvir Plus Sofosbuvir in Treatment-naive and Treatment-experienced Chronic Hepatitis C [Genotype 1, 2, 3, 4, 5, or 6] Subjects Coinfected With Human Immunodeficiency Virus [HIV]). Individual patient data from ALLY-2 were available; published summary data were extracted and pooled for the PHOTON trials. To adjust for cross trial differences, ALLY-2 patients were subject to the inclusion and exclusion criteria reported in the PHOTON trials and were weighted to match all available summary baseline characteristics reported in both PHOTON trials. Sustained virologic response at week 12 post-treatment (SVR12) discontinuation due to adverse events (AEs) and rates of AEs were compared. FINDINGS: The SVR12 rate was significantly higher among patients treated with DCV+SOF (n = 91) than among those treated with SOF+R (n = 455) both before (96.7% vs 84.6%; P = 0.002) and after (99.9% vs 84.6%; P < 0.001) adjusting for baseline characteristics. After adjustment, compared with patients treated with SOF+R, patients receiving DCV+SOF had a significantly lower rate of discontinuation due to AEs and significantly lower rates of the following specific AEs: cough, diarrhea, insomnia, nasopharyngitis, upper respiratory tract infection, and hemoglobin <10 g/dL. IMPLICATIONS: After adjustment for cross-trial differences in baseline characteristics, DCV+SOF was associated with a significantly higher SVR12 rate and lower rate of discontinuation due to AEs than SOF+R in patients coinfected with HIV and HCV. PMID- 26839047 TI - Performance success or failure is influenced by weeks lost to injury and illness in elite Australian track and field athletes: A 5-year prospective study. AB - OBJECTIVES: To investigate the impact of training modification on achieving performance goals. Previous research demonstrates an inverse relationship between injury burden and success in team sports. It is unknown whether this relationship exists within individual sport such as athletics. DESIGN: A prospective, cohort study (n=33 International Track and Field Athletes; 76 athlete seasons) across five international competition seasons. METHODS: Athlete training status was recorded weekly over a 5-year period. Over the 6-month preparation season, relationships between training weeks completed, the number of injury/illness events and the success or failure of a performance goal at major championships was investigated. Two-by-two table were constructed and attributable risks in the exposed (AFE) calculated. A mixed-model, logistic regression was used to determine the relationship between failure and burden per injury/illness. Receiver Operator Curve (ROC) analysis was performed to ascertain the optimal threshold of training week completion to maximise the chance of success. RESULTS: Likelihood of achieving a performance goal increased by 7-times in those that completed >80% of planned training weeks (AUC, 0.72; 95%CI 0.64-0.81). Training availability accounted for 86% of successful seasons (AFE=0.86, 95%CI, 0.46 to 0.96). The majority of new injuries occurred within the first month of the preparation season (30%) and most illnesses occurred within 2-months of the event (50%). For every modified training week the chance of success significantly reduced (OR=0.74, 95%CI 0.58 to 0.94). CONCLUSIONS: Injuries and illnesses, and their influence on training availability, during preparation are major determinants of an athlete's chance of performance goal success or failure at the international level. PMID- 26839048 TI - Homochiral D4-symmetric metal-organic cages from stereogenic Ru(II) metalloligands for effective enantioseparation of atropisomeric molecules. AB - Absolute chiral environments are rare in regular polyhedral and prismatic architectures, but are achievable from self-assembly of metal-organic cages/containers (MOCs), which endow us with a promising ability to imitate natural organization systems to accomplish stereochemical recognition, catalysis and separation. Here we report a general assembly approach to homochiral MOCs with robust chemical viability suitable for various practical applications. A stepwise process for assembly of enantiopure DeltaDeltaDeltaDeltaDeltaDeltaDeltaDelta- and LambdaLambdaLambdaLambdaLambdaLambdaLambdaLambda-Pd6(RuL3)8 MOCs is accomplished by pre-resolution of the Delta/Lambda-Ru-metalloligand precursors. The obtained Pd-Ru bimetallic MOCs feature in large D4-symmetric chiral space imposed by the predetermined Ru(II)-octahedral stereoconfigurations, which are substitutionally inert, stable, water-soluble and are capable of encapsulating a dozen guests per cage. Chiral resolution tests reveal diverse host-guest stereoselectivity towards different chiral molecules, which demonstrate enantioseparation ability for atropisomeric compounds with C2 symmetry. NMR studies indicate a distinctive resolution process depending on guest exchange dynamics, which is differentiable between host-guest diastereomers. PMID- 26839049 TI - Ferroelectric Metal in Tetragonal BiCoO3/BiFeO3 Bilayers and Its Electric Field Effect. AB - By first-principles calculations we investigate the electronic structure of tetragonal BiCoO3/BiFeO3 bilayers with different terminations. The multiferroic insulator BiCoO3 and BiFeO3 transform into metal in all of three models. Particularly, energetically favored model CoO2-BiO exhibits ferroelectric metallic properties, and external electric field enhances the ferroelectric displacements significantly. The metallic character is mainly associated to eg electrons, while t2g electrons are responsible for ferroelectric properties. Moreover, the strong hybridization between eg and O p electrons around Fermi level provides conditions to the coexistence of ferroelectric and metallic properties. These special behaviors of electrons are influenced by the interfacial electronic reconstruction with formed Bi-O electrovalent bond, which breaks OA-Fe/Co-OB coupling partially. Besides, the external electric field reverses spin polarization of Fe/Co ions efficiently, even reaching 100%. PMID- 26839050 TI - A switchable DNA origami nanochannel for regulating molecular transport at the nanometer scale. AB - A nanochannel with a shutter at one end was built by DNA nanotechnology. Using DNA hybridization the shutter could be opened or closed, influencing the transport of materials through the channel. This process was visualized by an enzyme cascade reaction occurring in the structure. PMID- 26839051 TI - BurnCase 3D software validation study: Burn size measurement accuracy and inter rater reliability. AB - OBJECTIVE: The aim of this study was to compare the accuracy of burn size estimation using the computer-assisted software BurnCase 3D (RISC Software GmbH, Hagenberg, Austria) with that using a 2D scan, considered to be the actual burn size. METHODS: Thirty artificial burn areas were pre planned and prepared on three mannequins (one child, one female, and one male). Five trained physicians (raters) were asked to assess the size of all wound areas using BurnCase 3D software. The results were then compared with the real wound areas, as determined by 2D planimetry imaging. To examine inter-rater reliability, we performed an intraclass correlation analysis with a 95% confidence interval. RESULTS: The mean wound area estimations of the five raters using BurnCase 3D were in total 20.7+/ 0.9% for the child, 27.2+/-1.5% for the female and 16.5+/-0.1% for the male mannequin. Our analysis showed relative overestimations of 0.4%, 2.8% and 1.5% for the child, female and male mannequins respectively, compared to the 2D scan. The intraclass correlation between the single raters for mean percentage of the artificial burn areas was 98.6%. There was also a high intraclass correlation between the single raters and the 2D Scan visible. CONCLUSION: BurnCase 3D is a valid and reliable tool for the determination of total body surface area burned in standard models. Further clinical studies including different pediatric and overweight adult mannequins are warranted. PMID- 26839052 TI - Developing a methodology to predict PM10 concentrations in urban areas using generalized linear models. AB - A methodology to predict PM10 concentrations in urban outdoor environments is developed based on the generalized linear models (GLMs). The methodology is based on the relationship developed between atmospheric concentrations of air pollutants (i.e. CO, NO2, NOx, VOCs, SO2) and meteorological variables (i.e. ambient temperature, relative humidity (RH) and wind speed) for a city (Barreiro) of Portugal. The model uses air pollution and meteorological data from the Portuguese monitoring air quality station networks. The developed GLM considers PM10 concentrations as a dependent variable, and both the gaseous pollutants and meteorological variables as explanatory independent variables. A logarithmic link function was considered with a Poisson probability distribution. Particular attention was given to cases with air temperatures both below and above 25 degrees C. The best performance for modelled results against the measured data was achieved for the model with values of air temperature above 25 degrees C compared with the model considering all ranges of air temperatures and with the model considering only temperature below 25 degrees C. The model was also tested with similar data from another Portuguese city, Oporto, and results found to behave similarly. It is concluded that this model and the methodology could be adopted for other cities to predict PM10 concentrations when these data are not available by measurements from air quality monitoring stations or other acquisition means. PMID- 26839053 TI - Seamless growth of a supramolecular carpet. AB - Organic/metal interfaces play crucial roles in the formation of intermolecular networks on metal surfaces and the performance of organic devices. Although their purity and uniformity have profound effects on the operation of organic devices, the formation of organic thin films with high interfacial uniformity on metal surfaces has suffered from the intrinsic limitation of molecular ordering imposed by irregular surface structures. Here we demonstrate a supramolecular carpet with widely uniform interfacial structure and high adaptability on a metal surface via a one-step process. The high uniformity is achieved with well-balanced interfacial interactions and site-specific molecular rearrangements, even on a pre-annealed amorphous gold surface. Co-existing electronic structures show selective availability corresponding to the energy region and the local position of the system. These findings provide not only a deeper insight into organic thin films with high structural integrity, but also a new way to tailor interfacial geometric and electronic structures. PMID- 26839054 TI - Long-Term (>10 Years) Prognostic Value of Dobutamine Stress Echocardiography in a High-Risk Cohort. AB - The prognostic value of dobutamine stress echocardiography (DSE) at >10-year follow-up is unknown. The aim of this study was to assess the very long-term prognostic value of DSE in a high-risk cohort of patients with known or suspected coronary artery disease. This prospective, single-center study included 3,381 patients who underwent DSE from January 1990 to January 2003. Two-dimensional echocardiographic images were acquired at rest, during dobutamine stress, and during recovery. Follow-up events were collected and included overall mortality, cardiac death, nonfatal myocardial infarction, and revascularization. The incremental value of DSE in the prediction of selected end points was evaluated using multivariate Cox proportional hazard analysis. During a mean follow-up of 13 +/- 3.2 years (range 7.3 to 20.5 years), there were 1,725 deaths (51%), of which 1,128 (33%) were attributed to cardiac causes. Patients with an abnormal DSE had a higher mortality rate (44% vs 35% at 15-year follow-up, p <0.001) than those with a normal DSE. When comparing echocardiographic variables at rest to variables at maximum dose dobutamine, the chi-square of the test improved from 842 to 870 (p <0.0001) and from 684 to 740 (p <0.0001) for all-cause mortality and cardiac death, respectively. DSE provided incremental value in predicting all cause mortality, cardiac death, and hard cardiac events. There seems, however, to be a "warranty period" of approximately 7 years, when the survival curves of a normal and abnormal DSE no longer diverge. PMID- 26839055 TI - Predicting Reaction Mechanisms and Potentials in Acid and Base from Self Consistent Quantum Theory: H(ads) and OH(ads) Deposition on the Pt(111) Electrode. AB - It has been shown recently that when reactants and products are well modeled within a comprehensive self-consistent theory for the electrochemical interface, accurate predictions are possible for reversible potentials, Urev, in acid electrolyte for reactions such as reduction of H(+)(aq) to form under potential deposited H(ads) and oxidation of an OH bond of H2O(ads) to deposit OH(ads). Predictions are based on calculated Gibbs energies for the reactant and product being equal at the reversible potential, which is the potential at the crossing point for reaction and product Gibbs energies, plotted as functions of electrode potential. In this Letter, it is demonstrated that the same capability holds for these reactions in basic electrolyte. This demonstration opens up the opportunity for predictions of reversible potentials and mechanisms for other electrocatalytic reactions in base. PMID- 26839056 TI - Degree of Anticoagulation Control in Patients With Atrial Fibrillation in Spain: Need to Minimize Biases and Contextualize Results. Response by Cinza Sanjurjo et al. PMID- 26839057 TI - Iron and Exercise in Heart Failure: How to Assess Relevant Changes? PMID- 26839059 TI - Simultaneously Load and Extended Release of Betamethasone and Ciprofloxacin from Vitamin E-Loaded Silicone-Based Soft Contact Lenses. AB - PURPOSE: The purpose of the present study was to evaluate the efficacy of commercial soft contact lenses, loaded with vitamin E, as ocular drug delivery systems for simultaneous loading and release of ciprofloxacin (Cipro) and betamethasone (BMZ) in artificial tears. METHODS: In this study, we applied vitamin E as a barrier to increase BMZ-Cipro loading into three commercial silicone-based soft contact lenses and control their simultaneous release into the artificial lachrymal fluid. Two different concentrations of vitamin E solution (0.1 and 0.2 g/ml) were used, and various parameters including changes in lens diameter, water content, ultraviolet-visible light (UV-Vis) transmittance, drug-binding properties, and drug release profile were investigated. RESULTS: The obtained results indicated that vitamin E significantly reduced the swelling properties of contact lenses in aqueous media, while it enhanced the lens diameter in both dry and hydrated states. Vitamin E had no significant effects on visible transmittance, while it blocked UV radiation, which could be harmful for the eye surface. Our findings revealed that vitamin E improved the simultaneous loading amount of BMZ-Cipro into soft contact lenses. Additionally, BMZ and Cipro release rates significantly reduced after using vitamin E as a hydrophobic diffusion barrier. After soaking the lenses in 0.1 and 0.2 g/ml of vitamin E solution, BMZ release time increased by 28.8-81.6 and 182.4-201 folds, respectively. Moreover, Cipro release time increased by 12 18 and 1152-2313 folds, respectively. CONCLUSION: The results of the present study indicated the efficacy of vitamin E as a diffusion barrier in developing a controlled drug delivery system for the simultaneous loading of BMZ and Cipro and sustaining their release from soft contact lenses. PMID- 26839060 TI - Biomechanical comparison of the human cadaveric pelvis with a fourth generation composite model. AB - The use of cadavers for orthopaedic biomechanics research is well established, but presents difficulties to researchers in terms of cost, biosafety, availability, and ease of use. High fidelity composite models of human bone have been developed for use in biomechanical studies. While several studies have utilized composite models of the human pelvis for testing orthopaedic reconstruction techniques, few biomechanical comparisons of the properties of cadaveric and composite pelves exist. The aim of this study was to compare the mechanical properties of cadaveric pelves to those of the 4th generation composite model. An Instron ElectroPuls E10000 mechanical testing machine was used to load specimens with orientation, boundary conditions and degrees of freedom that approximated those occurring during the single legged phase of walking, including hip abductor force. Each specimen was instrumented with strain gauge rosettes. Overall specimen stiffness and principal strains were calculated from the test data. Composite specimens showed significantly higher overall stiffness and slightly less overall variability between specimens (composite K=1448+/-54N/m, cadaver K=832+/-62N/m; p<0.0001). Strains measured at specific sites in the composite models and cadavers were similar (but did differ) only when the applied load was scaled to overall construct stiffness. This finding regarding strain distribution and the difference in overall stiffness must be accounted for when using these composite models for biomechanics research. Altering the cortical wall thickness or tuning the elastic moduli of the composite material may improve future generations of the composite model. PMID- 26839058 TI - Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders. AB - Intracellular trafficking of receptor proteins is essential for neurons to detect various extracellular factors during the formation and refinement of neural circuits. However, the precise mechanisms underlying the trafficking of neurotrophin receptors to synapses remain elusive. Here, we demonstrate that a brain-enriched sorting nexin, ARHGAP33, is a new type of regulator for the intracellular trafficking of TrkB, a high-affinity receptor for brain-derived neurotrophic factor. ARHGAP33 knockout (KO) mice exhibit reduced expression of synaptic TrkB, impaired spine development and neuropsychiatric disorder-related behavioural abnormalities. These deficits are rescued by specific pharmacological enhancement of TrkB signalling in ARHGAP33 KO mice. Mechanistically, ARHGAP33 interacts with SORT1 to cooperatively regulate TrkB trafficking. Human ARHGAP33 is associated with brain phenotypes and reduced SORT1 expression is found in patients with schizophrenia. We propose that ARHGAP33/SORT1-mediated TrkB trafficking is essential for synapse development and that the dysfunction of this mechanism may be a new molecular pathology of neuropsychiatric disorders. PMID- 26839061 TI - FDG PET/CT imaging of metastatic renal squamous cell carcinoma. PMID- 26839062 TI - Unusual dimer formation of cyclometalated ruthenium NHC p-cymene complexes. AB - We present the synthesis and structural characterization of novel ruthenium complexes containing C^C* cyclometalated N-heterocyclic carbene ligands, eta(6) arene (p-cymene) ligands and one bridging chlorine ion. Complexes of the general formula [Ru(p-cymene)(C^C*)Cl] were prepared via a one-pot synthesis using in situ transmetalation from the correspondent silver NHC complexes. These complexes react with sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBAr(F)4) to form dinuclear complexes of the general structure [Ru(p-cymene)(C^C*)-MU-Cl-(p cymene)(C^C*)Ru](+)[BAr(F)4](-). Solid-state structures confirm that the pseudo tetrahedral coordination around the metal center with the eta(6)-ligand aligned perpendicularly to the C^C* ligand and the i-Pr group "atop" is retained in the bimetallic complexes. PMID- 26839063 TI - A novel mutation in GLUD1 causing hyperinsulinism-hyperammonemia in a patient with high density of homozygosity on microarray: a case report. AB - BACKGROUND: Hyperinsulinism-hyperammonemia syndrome is the second most common cause of congenital hyperinsulinism and is easily treated with diazoxide; however, the symptoms in our patient were very difficult to control with typical medical therapy. To the best of our knowledge, neither our patient's mutation, nor a case of hyperinsulinism-hyperammonemia presenting with dysmorphic features and intrauterine growth restriction has previously been reported. CASE PRESENTATION: We describe a 2-year-old Hispanic girl with an unusual presentation of dysmorphic features and intrauterine growth restriction who was later found to have hyperinsulinism-hyperammonemia syndrome. Chromosomal microarray analysis revealed no copy number variants but demonstrated a high density of noncontiguous regions of homozygosity consistent with limited outbreeding. Sequencing of her GLUD1 gene revealed a previously undescribed mutation of cytosine to thymine at position 1519 resulting in an amino acid change of histidine to tyrosine at position 507. Although no functional studies were performed, function prediction tools in combination with our patient's phenotype support the hypothesis that the mutation is deleterious. Despite treatment with a maximum dose of diazoxide (15 mg/kg/day), phenobarbital (8.5 mg/kg/day divided twice daily) and a protein restricted diet, she has global developmental delay, and continues to have seizures and recurrent episodes of hypoglycemia. CONCLUSIONS: It remains unclear if her clinical presentation can be solely explained by hyperinsulinism hyperammonemia syndrome or is the result of an undiagnosed recessive disorder related to her homozygosity. It is our hope that clinicians may learn from our patient when formulating treatment plans for refractory cases of hyperinsulinism hyperammonemia and avoid the morbidities associated with delayed diagnosis and treatment. PMID- 26839064 TI - OxyR Is a Key Regulator in Response to Oxidative Stress in Streptomyces avermitilis. AB - The role of the H2O2-sensing transcriptional regulator OxyR in oxidative stress responses in Streptomyces avermitilis was investigated. An oxyR deletion mutant was more sensitive to H2O2 and tert-butyl hydroperoxide than was the wild-type strain, indicating that OxyR mediates the defensive system against H2O2 and organic peroxide. Evidence presented herein suggests that in cells treated with exogenous H2O2, the oxidized form of OxyR activated expression of ahpCD by binding to a palindromic sequence of the promoter region. Oxidized OxyR also induced expression of other antioxidant enzymes (KatA1, KatA2, KatA3, OhrB1) and oxidative stress regulators (CatR, OhrR, sigmaR). The thiol-oxidative stress regulator gene sigR was regulated at the transcription level by OxyR. We conclude that OxyR is necessary to activate transcription of sigR from the sigmaR dependent promoter to express an unstable larger isoform of sigmaR during oxidative stress. In response to oxidative stress, OxyR facilitates rapid production of H2O2-scavenging enzymes to repair oxidative damage through direct regulation and cascaded regulation of CatR, OhrR, and sigmaR. PMID- 26839065 TI - Development of the atrial septum. PMID- 26839067 TI - Is colchicine a promising novel treatment option for cardiovascular medicine? PMID- 26839066 TI - Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation. AB - OBJECTIVE: Atrial fibrillation (AF) is a risk factor for stroke and mortality and the prothrombotic state has been linked to inflammation. In this study we evaluated the relationship between inflammatory biomarkers at baseline and future risk of cardiovascular events in the Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. METHODS: The ARISTOTLE trial randomised 18,201 patients with AF to apixaban or warfarin. Interleukin 6 (IL-6) and C reactive protein (CRP) were analysed in plasma obtained at randomisation from 14,954 participants, and median follow-up was 1.9 years. Association between quartile groups of IL-6 and CRP and outcomes were analysed by Cox regression adjusted for clinical risk factors and other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). RESULTS: The IL-6 median level was 2.3 ng/L (IQR 1.5-3.9), median CRP level was 2.2 mg/L (1.0 4.8). IL-6 and CRP were significantly associated with all-cause mortality independent of clinical risk factors and other biomarkers (HR (95% CI) 1.93 (1.57 to 2.37) and 1.49 (1.24 to 1.79), respectively, Q4 vs Q1). IL-6 was associated with myocardial infarction, cardiovascular mortality, and major bleeding beyond clinical risk factors but not in the presence of cardiovascular biomarkers (NT proBNP, troponin, GDF-15, cystatin C). Neither inflammatory biomarker was associated with stroke/systemic embolism. Risk prediction for stroke, death and major bleeding was not improved by IL-6 or CRP when added to clinical risk factors and the other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). CONCLUSIONS: In patients with AF on anticoagulation, after accounting for clinical risk factors and other biomarkers, biomarkers of inflammation were significantly associated with an increased risk of mortality. However, there were no associations with the risk of stroke or major bleeding. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT00412984 post results. PMID- 26839068 TI - Development of the atrial septum. PMID- 26839069 TI - Clinical importance of detecting exaggerated blood pressure response to exercise on antihypertensive therapy. AB - OBJECTIVE: In patients with hypertension, regression of left ventricular hypertrophy (LVH) is associated with improved prognosis. Impact of exaggerated blood pressure response to exercise (Ex-BP) seen in patients with hypertension undergoing antihypertensive therapy on the regression of LVH has not been evaluated. This prospective study investigated the relationship between Ex-BP on antihypertensive therapy and the regression of LVH. METHODS: We prospectively studied 124 never-treated patients with hypertension with LVH. After a pretreatment evaluation, antihypertensive treatment was started and exercise test was performed in all patients. Patients with Ex-BP were divided into the Ex-BP (+) group and those without were divided into the Ex-BP (-) group. Regression of LVH over the follow-up period was compared between the groups. RESULTS: The follow-up duration was approximately 12 months in both the groups. Mean values of blood pressure at rest during the follow-up period were similar between the groups. Reduction of LVH was seen in both the groups. The magnitude of reduction of LVH was significantly smaller in the Ex-BP (+) group compared with the Ex-BP ( ) group. Regression of LVH was much frequently seen in the Ex-BP (+) group compared with the Ex-BP (-) group. Multiple regression analysis determined that on-treatment Ex-BP was an independent negative determinant of antihypertensive treatment-induced reduction of LVH. CONCLUSIONS: This study suggests that on treatment Ex-BP is associated with depressed regression of LVH in patients with hypertension with antihypertensive treatment. If Ex-BP is detected despite receiving antihypertensive agents, improvement of Ex-BP may be necessary to achieve an effective reduction of LVH. Active search of Ex-BP is recommended in patients with hypertension with antihypertensive treatment. PMID- 26839070 TI - Gut-associated lymphoid tissue, gut microbes and susceptibility to experimental autoimmune encephalomyelitis. AB - Gut microbiota and gut-associated lymphoid tissue have been increasingly appreciated as important players in pathogenesis of various autoimmune diseases, including multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis that can be induced with an injection of spinal cord homogenate emulsified in complete Freund's adjuvant in Dark Agouti (DA) rats, but not in Albino Oxford (AO) rats. In this study, mesenteric lymph nodes (MLN), Peyer's patches (PP) and gut microbiota were analysed in these two rat strains. There was higher proportion of CD4(+) T cells and regulatory T cells in non-immunised DA rats in comparison to AO rats. Also, DA rat MLN and PP cells were higher producers of pro-inflammatory cytokines interferon-gamma and interleukin-17. Finally, microbial analyses showed that uncultivated species of Turicibacter and Atopostipes genus were exclusively present in AO rats, in faeces and intestinal tissue, respectively. Thus, it is clear that in comparison of an EAE-susceptible with an EAE-resistant strain of rats, various discrepancies at the level of gut associated lymphoid tissue, as well as at the level of gut microbiota can be observed. Future studies should determine if the differences have functional significance for EAE pathogenesis. PMID- 26839071 TI - Lactobacillus plantarum CUL66 can impact cholesterol homeostasis in Caco-2 enterocytes. AB - Hypercholesterolemia drives the development of cardiovascular disease, the leading cause of mortality in western society. Supplementation with probiotics that interfere with cholesterol metabolism may provide a contribution to disease prevention. Lactobacillus plantarum CUL66 (NCIMB 30280) has been assessed in vitro for its ability to impact cholesterol absorption. L. plantarum CUL66 tested positive for bile salt hydrolase activity and the ability to assimilate cholesterol from culture media. RT-qPCR analysis showed that the bacterium significantly decreased the expression of Niemann-Pick C1-like 1 and ATP-binding cassette transporter-1 in polarised Caco-2 cells after 6 h exposure. Conversely, the expression of ATP-binding cassette sub-family G member (ABCG)-5 and ABCG-8, and 3-hydroxy-3-methylglutaryl-CoA reductase were significantly increased. Using a radiolabelled assay, we also observed significant reductions in the uptake and basolateral efflux of cholesterol by Caco-2 cells exposed to L. plantarum CUL66. This in vitro study identified L. plantarum CUL66 as a cholesterol lowering bacteria by highlighting its ability to beneficially regulate multiple in vitro events associated with intestinal cholesterol metabolism and provides evidence of efficacy for its inclusion in future in vivo studies. PMID- 26839073 TI - Glucolytic fingerprinting reveals metabolic groups within the genus Bifidobacterium: an exploratory study. AB - Microorganisms of the genus Bifidobacterium are inhabitants of diverse niches including the digestive tract of humans and animals. The species Bifidobacterium adolescentis, Bifidobacterium animalis, Bifidobacterium bifidum, Bifidobacterium breve and Bifidobacterium longum have qualified presumption of safety status granted by EFSA and several strains are considered probiotic, and are being included in functional dairy fermented products. In the present work we carried out a preliminary exploration of general metabolic characteristics and organic acid production profiles of a reduced number of strains selected from these and other species of the genus Bifidobacterium. The use of resting cells allowed obtaining metabolic fingerprints without interference of metabolites accumulated during growth in culture media. Acetic acid was the most abundant organic acid formed per mol of glucose consumed (from 1.07 +/- 0.03 to 1.71 +/- 0.22 mol) followed by lactic acid (from 0.34 +/- 0.06 to 0.90 +/- 0.12 mol), with moderate differences in production among strains; pyruvic, succinic and formic acids were also produced at considerably lower proportions, with variability among strains. The acetic to lactic acid ratio showed lower values in stationary phase as regard to the exponential phase for most, but not all, the microorganisms; this was due to a decrease in acetic acid molar proportions together with increases of lactic acid proportions in stationary phase. A linear discriminant analysis allowed to cluster strains into species with 51-100% probability, evidencing different metabolic profiles, according to the relative production of organic acids from glucose by resting cells, of microorganisms collected at the exponential phase of growth. Looking for a single metabolic marker that could adequately discriminate metabolic groups, we found that groups established by the acetic to lactic acid ratio fit well with differences previously evidenced by the discriminant analysis. The proper establishment of metabolic groups within the genus Bifidobacterium could help to select the best suited probiotic strains for specific applications. PMID- 26839074 TI - The case in favour of probiotics before, during and after pregnancy: insights from the first 1,500 days. AB - Successful human reproduction requires microbial homeostasis in the female reproductive tract, and colonisation of the newborn with beneficial microbes. In order to prevent several complications associated with dysbiosis, the administration of probiotics is more often being considered. The objective of the enclosed review was to examine the rationale for probiotic utility before and during pregnancy and in the early phase of infant life. The conclusions emerged from a panel of researchers who met during the International Scientific Association for Probiotics and Prebiotics (ISAPP) workshop held in Washington, DC, USA in 2015. The group concluded based upon the current literature, that a case can be made for the use of a specific sets of probiotic organisms during the first 1,500 days of life, with the goal of a healthy pregnancy to term, and a healthy start to life with lowered risk of infections and inflammatory events. The key to successfully translating these recommendations to practice is that products be made available and affordable to women in developed and developing countries. PMID- 26839075 TI - Bifidobacterium bifidum R0071 decreases stress-associated diarrhoea-related symptoms and self-reported stress: a secondary analysis of a randomised trial. AB - Psychological stress is associated with gastrointestinal (GI) distress. This secondary analysis from a randomised, double-blind, placebo-controlled study examined whether three different probiotics could normalise self-reported stress associated GI discomfort and reduce overall self-reported stress. Undergraduate students (n=581) received Lactobacillus helveticus R0052, Bifidobacterium longum ssp. infantis R0033, Bifidobacterium bifidum R0071, or placebo. Participants self reported 2 outcomes for a 6-week period, which included final academic exams: daily level of stress (0=no stress to 10=extremely stressed) and weekly three diarrhoea-related symptoms (DS, 1=no discomfort to 7=severe discomfort) using the GI Symptom Rating Scale. Self-reported stress was positively related to DS (P=0.0068). Mean DS scores were lower with B. bifidum versus placebo at week 2 at the average level of stress and the average body mass index (BMI). DS scores were lower with B. bifidum at week 5 versus week 0 and 1 and with B. infantis R0033 at week 6 versus week 0. DS scores were higher when antibiotics were used in the prior week with placebo (P=0.0092). DS were not different with or without antibiotic use with the probiotics. Only B. bifidum had an effect on self reported stress scores (P=0.0086). The self-reported stress score was also dependent on hours of sleep per day where it decreased by 0.13 for each additional hour of sleep. During a stressful period, B. bifidum R0071 decreases DS and self-reported stress scores. This trial was registered at clinicaltrials.gov as NCT01709825. PMID- 26839076 TI - Effects of heat-killed Lactobacillus kunkeei YB38 on human intestinal environment and bowel movement: a pilot study. AB - It is well known that lactic acid bacteria supplementation is beneficial for intestinal conditions such as microbiota; however, the effects of killed-lactic acid bacteria on intestinal conditions are largely unclear. This study aimed to evaluate the effect of heat-killed Lactobacillus kunkeei YB38 (YB38) at a dose of approximately 10 mg/day on human intestinal environment and bowel movement. This single-blind study enrolled 29 female subjects with a low defecation frequency who consumed heat-killed YB38 at four increasing dosage levels: 0 (placebo), 2, 10, and 50 mg. Each dose was consumed daily for two weeks, with a two-week baseline period preceding the dosing-period and a two-week washout period ending the study. Observed levels of Bacteroides fragilis group significantly decreased with intake of heat-killed YB38 at >=10 mg/day compared with levels during placebo intake (P<0.01). Faecal pH significantly decreased with 10 and 50 mg/day intake (P<0.01 and 0.05, respectively). Acetic acid levels tended to increase in faeces at the 50 mg/day dose (P<0.1). Bowel movement tended to increase in all heat-killed YB38 intake periods (P<0.1). In conclusion, heat-killed YB38 altered human intestinal microbiota at doses of >=10 mg/day and tended to increase bowel movement at >=2 mg/day. This is the first study to show the intestinal microbiota altering effect of L. kunkeei and to report the bowel movement-improving effect of heat-killed lactic acid bacteria. PMID- 26839077 TI - Synthesis of Nanoscale Coordination Polymers in Femtoliter Reactors on Surfaces. AB - In the present work, AFM-assisted lithography was used to perform the synthesis of a coordination polymer inside femtoliter droplets deposited on surfaces. For this, solutions of the metal salt and the organic ligand were independently transferred to adjacent tips of the same AFM probe array and were sequentially delivered on the same position of the surface, creating femtoliter-sized reaction vessels where the coordination reaction and particle growth occurred. Alternatively, the two reagents were mixed in the cantilever array by loading an excess of the inks, and transferred to the surface immediately after, before the precipitation of the coordination polymer took place. The in situ synthesis allowed the reproducible obtaining of round-shaped coordination polymer nanostructures with control over their XY positioning on the surface, as characterized by microscopy and spectroscopy techniques. PMID- 26839072 TI - High purity galacto-oligosaccharides enhance specific Bifidobacterium species and their metabolic activity in the mouse gut microbiome. AB - Prebiotics are selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon the host health. The aim of this study was to evaluate the influence of a beta(1-4)galacto-oligosaccharides (GOS) formulation consisting of 90% pure GOS (GOS90), on the composition and activity of the mouse gut microbiota. Germ-free mice were colonised with microbiota from four pathogen-free wt 129 mice donors (SPF), and stools were collected during a feeding trial in which GOS90 was delivered orally for 14 days. Pyrosequencing of 16S rDNA amplicons showed that Bifidobacterium and specific Lactobacillus, Bacteroides and Clostridiales were more prevalent in GOS90-fed mice after 14 days, although the prebiotic impact on Bifidobacterium varied among individual mice. Prebiotic feeding also resulted in decreased abundance of Bacteroidales, Helicobacter and Clostridium. High-throughput quantitative PCR showed an increased abundance of Bifidobacterium adolescentis, Bifidobacterium pseudocatenulatum, Bifidobacterium lactis and Bifidobacterium gallicum in the prebiotic-fed mice. Control female mice showed a higher diversity (phylogenetic diversity (PD) = 15.1 +/- 3.4 in stools and PD = 13.0 +/- 0.6 in intestinal contents) than control males (PD = 7.8 +/- 1.6 in stool samples and PD = 9.5 +/- 1.0 in intestinal contents). GOS90 did not modify inflammatory biomarkers (interleukin (IL)-6, IL-12, IL-1beta, interferon gamma and tumour necrosis factor alpha). Decreased butyrate, acetate and lactate concentrations in stools of prebiotic fed mice suggested an increase in colonic absorption and reduced excretion. Overall, our results demonstrate that GOS90 is capable of modulating the intestinal microbiome resulting in expansion of the probiome (autochtonous commensal intestinal bacteria considered to have a beneficial influence on health). PMID- 26839080 TI - Characterization of an FTLD-PDB family with the coexistence of SQSTM1 mutation and hexanucleotide (G4C2) repeat expansion in C9orf72 gene. AB - The C9orf72 expansion is considered a major genetic cause of familial frontotemporal dementia (FTD) in several patients' cohorts. Interestingly, C9orf72 expansion carriers, present also abundant neuronal p62-positive inclusions. Although p62/SQSTM1 mutations were initially associated with Paget disease of bone (PDB), they have been also identified in FTD. We describe an FTD PDB family in which the proband presented with behavioral FTD phenotype and concomitant Paget disease. The molecular genetic analysis revealed the co occurrence of 2 mutations; the pathogenic C9orf72 expansion and p.P392L heterozygous missense mutation in SQSTM1 gene. Amongst the 6 family members analyzed, the p.P392L SQSTM1 mutation segregated as expected with PDB, whereas the C9orf72 expansion segregated with frontal cognitive impairment or dementia in all but one carrier. The coexistence of these conditions could be underestimated since neither patients with FTD nor patients with PDB undergo bone scintigraphy or cognitive assessment, respectively. The number of cases with double mutations could also be over looked as the molecular strategy adopted in most laboratories ends with the identification of one pathogenic mutation in one of the known causative genes. Therefore, we advocate for further clinical and molecular evaluation in suspect cases. PMID- 26839079 TI - Expression and purification of an engineered, yeast-expressed Leishmania donovani nucleoside hydrolase with immunogenic properties. AB - Leishmania donovani is the major cause of visceral leishmaniasis (kala-azar), now recognized as the parasitic disease with the highest level of mortality second only to malaria. No human vaccine is currently available. A 36 kDa L. donovani nucleoside hydrolase (LdNH36) surface protein has been previously identified as a potential vaccine candidate antigen. Here we present data on the expression of LdNH36 in Pichia pastoris and its purification at the 20 L scale to establish suitability for future pilot scale manufacturing. To improve efficiency of process development and ensure reproducibility, 4 N-linked glycosylation sites shown to contribute to heterogeneous high-mannose glycosylation were mutated to glutamine residues. The mutant LdNH36 (LdNH36-dg2) was expressed and purified to homogeneity. Size exclusion chromatography and light scattering demonstrated that LdNH36-dg2 existed as a tetramer in solution, similar to the wild-type recombinant L. major nucleoside hydrolase. The amino acid mutations do not affect the tetrameric interface as confirmed by theoretical modeling, and the mutated amino acids are located outside the major immunogenic domain. Immunogenic properties of the LdNH36-dg2 recombinant protein were evaluated in BALB/c mice using formulations that included a synthetic CpG oligodeoxynucleotide, together with a microparticle delivery platform (poly(lactic-co-glycolic acid)). Mice exhibited high levels of IgG1, IgG2a, and IgG2b antibodies that were reactive to both LdNH36-dg2 and LdNH36 wild-type. While the point mutations did affect the hydrolase activity of the enzyme, the IgG antibodies elicited by LdNH36-dg2 were shown to inhibit the hydrolase activity of the wild-type LdNH36. The results indicate that LdNH36-dg2 as expressed in and purified from P. pastoris is suitable for further scale-up, manufacturing, and testing in support of future first-in-humans phase 1 clinical trials. PMID- 26839078 TI - Altered periaqueductal gray resting state functional connectivity in migraine and the modulation effect of treatment. AB - The aims of this study were to 1) compare resting state functional connectivity (rs-fc) of the periaqueductal gray (PAG), a key region in the descending pain modulatory system (DPMS) between migraine without aura (MwoA) patients and healthy controls (HC), and 2) investigate how an effective treatment can influence the PAG rs-fc in MwoA patients. One hundred MwoA patients and forty-six matched HC were recruited. Patients were randomized to verum acupuncture, sham acupuncture, and waiting list groups. Resting state fMRI data were collected and seed based functional connectivity analysis was applied. Compared with HC, MwoA patients showed reduced rs-fc between the PAG and rostral anterior cingulate cortex/medial prefrontal cortex (rACC/mPFC), key regions in the DPMS and other pain related brain regions. The reduced rs-fc between the PAG and rACC/mPFC was associated with increased migraine headache intensity at the baseline. After treatments, rs-fc between the PAG and the rACC in MwoA patients significantly increased. The changes of rs-fc among the PAG, rACC and ventral striatum were significantly associated with headache intensity improvement. Impairment of the DPMS is involved in the neural pathophysiology of migraines. Impaired DPMS in migraine patients can be normalized after effective treatment. PMID- 26839081 TI - Human spinal autografts of olfactory epithelial stem cells recapitulate donor site histology, maintaining proliferative and differentiation capacity many years after transplantation. PMID- 26839083 TI - Effectiveness of allergic rhinitis treatments in real-life with a focus on MP AzeFlu. AB - For any allergic rhinitis (AR) treatment, it is crucial to provide evidence not only of efficacy (assessed in randomized controlled trials (RCTs)) but also of effectiveness in real-life. Observational studies provide valuable data on the use and results associated with interventions prescribed in real-life. However, real-life evidence supporting available AR treatment options is sparse with effectiveness only established for oral antihistamines (desloratadine, ebastine), intranasal corticosteroids (mometasone furoate, fluticasone propionate (FP)), allergen immunotherapy and omalizumab. A novel intranasal formulation of azelastine hydrochloride and FP in a single spray (MP-AzeFlu) shows great promise, with the effectiveness observed in real-life exceeding that noted in RCTs. This review summarises real-life data on MP-AzeFlu, which provides rapid and sustained symptom control irrespective of patient age, AR phenotype or disease severity. We call for high quality real-life research in addition to RCTs to inform future AR treatment guidelines. PMID- 26839082 TI - Proaggregant nuclear factor(s) trigger rapid formation of alpha-synuclein aggregates in apoptotic neurons. AB - Cell-to-cell transmission of alpha-synuclein (alphaS) aggregates has been proposed to be responsible for progressive alphaS pathology in Parkinson disease (PD) and related disorders, including dementia with Lewy bodies. In support of this concept, a growing body of in vitro and in vivo experimental evidence shows that exogenously introduced alphaS aggregates can spread into surrounding cells and trigger PD-like pathology. It remains to be determined what factor(s) lead to initiation of alphaS aggregation that is capable of seeding subsequent propagation. In this study we demonstrate that filamentous alphaS aggregates form in neurons in response to apoptosis induced by staurosporine or other toxins-6 hydroxy-dopamine and 1-methyl-4-phenylpyridinium (MPP+). Interaction between alphaS and proaggregant nuclear factor(s) is associated with disruption of nuclear envelope integrity. Knocking down a key nuclear envelop constituent protein, lamin B1, enhances alphaS aggregation. Moreover, in vitro and in vivo experimental models demonstrate that aggregates released upon cell breakdown can be taken up by surrounding cells. Accordingly, we suggest that at least some alphaS aggregation might be related to neuronal apoptosis or loss of nuclear membrane integrity, exposing cytosolic alpha-synuclein to proaggregant nuclear factors. These findings provide new clues to the pathogenesis of PD and related disorders that can lead to novel treatments of these disorders. Specifically, finding ways to limit the effects of apoptosis on alphaS aggregation, deposition, local uptake and subsequent propagation might significantly impact progression of disease. PMID- 26839084 TI - Broad Scope Aminocyclization of Enynes with Cationic JohnPhos-Gold(I) Complex as the Catalyst. AB - A practical aminocyclization of 1,6-enynes with a wide variety of substituted anilines, including N-alkyl anilines, has been achived by using cationic [JohnPhosAu(MeCN)]SbF6 as a general purpose catalyst. The resulting adducts can be easily converted into polycyclic compounds by palladium- and gold-catalyzed reactions. PMID- 26839085 TI - An analysis of the validity and utility of the proximon proposition. AB - The utilization of metagenomic functional interactions represents a key technique for metagenomic functional annotation efforts. By definition, metagenomic operons represent such interactions, but many operon predictions protocols rely on information about orthology and/or gene function that is frequently unavailable for metagenomic genes. Recently, the concept of the metagenomic proximon was proposed for use in metagenomic scenarios where supplemental information is sparse. In this paper, we examine the validity and utility of the proximon proposition by measuring the extent to which proximons emulate actual operons. Using the Escherichia coli K-12 genome, we compare proximons and operons from the same genome and observe the configurations and cardinalities among their corresponding mappings. The results demonstrate that the vast majority of proximons map discretely to a single operon in a conservative fashion where a typical proximon is synonymous to an equivalent or truncated operon. However, a large proportion of operons had no corresponding mappings to any proximon. Various perspectives of operon and proximon intersection are discussed, along with the potential limitations for proximon detection and usage. PMID- 26839086 TI - New PCR diagnostic systems for the detection and quantification of porcine cytomegalovirus (PCMV). AB - Pigs are frequently infected with porcine cytomegalovirus (PCMV). Infected adult animals may not present with symptoms of disease, and the virus remains latent. However, the virus may be transmitted to human recipients receiving pig transplants. Recently, it was shown that pig-to-non-human-primate xenotransplantations showed 2 to 3 times lower transplant survival when the donor pig was infected with PCMV. Therefore, highly sensitive methods are required to select virus-free pigs and to examine xenotransplants. Seven previously established PCR detection systems targeting the DNA polymerase gene of PCMV were examined by comparison of thermodynamic parameters of oligonucleotides, and new diagnostic nested PCR and real-time PCR systems with improved parameters and high sensitivity were established. The detection limit of conventional PCR was estimated to be 15 copies, and that of the nested PCR was 5 copies. The sensitivity of the real-time PCR with a TaqMan probe was two copies. An equal efficiency of the newly established detection systems was shown by parallel testing of DNA from sera and blood of six pigs, identifying the same animals as PCMV infected. These new diagnostic PCR systems will improve the detection of PCMV and therefore increase the safety of porcine xenotransplants. PMID- 26839087 TI - Erratum to: Immunogenicity and antigenic relationships among spike proteins of porcine epidemic diarrhea virus subtypes G1 and G2. PMID- 26839088 TI - MPs pass innovative medicines bill. PMID- 26839090 TI - Fe3C-filled carbon nanotubes: permanent cylindrical nanomagnets possessing exotic magnetic properties. AB - The present study aims to deduce the confinement effect on the magnetic properties of iron carbide (Fe3C) nanorods filled inside carbon nanotubes (CNTs), and to document any structural phase transitions that can be induced by compressive/tensile stress generated within the nanorod. Enhancement in the magnetic properties of the nanorods is attributed to tensile stress as well as to compression, present in the radial direction and along the nanotube axis, respectively. Finally, the growth of permanent cylindrical nanomagnets has been optimized by applying a field gradient. Besides presenting the growth model of in situ filling, we have also proposed the mechanism of magnetization of the nanotubes. Magnetization along the tube axis has been probed by confirming the pole formation. Fe3C has been selected because of its ease of formation, low TC and incompressibility. PMID- 26839089 TI - Economic evaluations of fluticasone-propionate/salmeterol combination therapy for chronic obstructive pulmonary disease: a review of published studies. AB - This review identifies and evaluates the comprehensive reporting of peer-reviewed economic evaluations of the effectiveness of fluticasone-propionate/salmeterol combination (FSC) therapy for maintenance treatment of chronic obstructive pulmonary disease (COPD). Economic evaluations were included if published in English since 2003. Evaluation categories included in the review were cost effectiveness, cost-utility, and cost-consequence analyses. FSC is cost-effective in comparison to short-acting bronchodilators (SABDs). Cost and outcome differences between FSC and other long-acting therapies were modest. Studies exhibited large variations in populations, designs and environment, limiting the ability to draw conclusions. Many new maintenance treatments for COPD have been approved since 2010. Most have yet to be compared to older treatments like FSC. Evaluations are needed that consider costs and outcomes from a societal perspective (e.g., patients' ability to keep working) and evaluations that include subgroup analyses to investigate differential impacts according to clusters of patient characteristics. PMID- 26839091 TI - Evaluation of the glucocorticoid, mineralocorticoid, and adrenal androgen secretion dynamics in a large cohort of patients aged 6-18 years with transfusion dependent beta-thalassemia major, with an emphasis on the impact of cardiac iron load. AB - The variable presence of adrenal insufficiency (AI) due to hypocortisolemia (HC) in patients with thalassemia is well established; however, the prevalence of adrenocortical hypofunction (ACH) in the zona glomerulosa and zona reticularis of the adrenal cortex is unknown. To establish the prevalence of ACH, we examined the cortisol response to 1-ug and 250-ug ACTH tests, plasma aldosterone (A)/plasma renin activity (PRA) ratio, and serum dehydroepiandrosterone sulfate (DHEAS) levels in a large cohort of patients with thalassemia, and to investigate the impact of total body iron load (TBIL) on adrenocortical function. The setting used was University hospital and government-based tertiary care center. One hundred twenty-one (52 females) patients with beta-thalassemia major (beta-TM) and 72 healthy peers (38 females) were enrolled. The patients underwent a 250-ug cosyntropin test if their peak cortisol was <500 nmol/L in a 1-ug cosyntropin test. Magnetic resonance imaging (MRI) was performed to assess the MRI-based liver iron content and cardiac MRI T2* iron. The associations between ACH and TBIL were investigated. The patients with thalassemia had lower ACTH, cortisol, DHEAS, and A/PRA values compared with the controls (p < 0.001). Thirty-nine patients (32.2 %) had HC [primary (n = 1), central (n = 36), combined (n = 2)], and 47 (38.8 %) patients had reduced DHEAS levels; 29 (24.0 %) patients had reduced A/PRA ratios. Forty-six (38.0 %) patients had hypofunction in one of the adrenal zones, 26 (21.5 %) had hypofunction in two adrenal zones, and 9 (7.4 %) had hypofunction in all three zones. Patient age and TBIL surrogates were significant independent parameters associated with ACH. Cardiac MRI T2* iron was the only significant parameter that predicted the severity of ACH at a cut-off of 20.6 ms, with 81 % sensitivity and 78 % specificity. Patients with thalassemia have a high prevalence of AI due to HC and zona glomerulosa and zona reticularis hypofunction. TBIL surrogates can predict ACH, but cardiac iron was the only surrogate that was adequately sensitive to predict the severity of ACH. PMID- 26839092 TI - Products of gut-microbial tryptophan metabolism inhibit the steroid hormone synthesizing cytochrome P450 11A1. PMID- 26839094 TI - HER2 Assessment in Upper Gastrointestinal Tract Adenocarcinoma: A Practical, Algorithmic Approach. AB - Gastric and gastroesophageal junction adenocarcinomas constitute a major health problem. For localized disease, adjuvant treatment is multidisciplinary and usually includes a combination of surgery, radiation and chemotherapy. Recently, trastuzumab (Herceptin) has been approved for the treatment of metastatic upper gastrointestinal (GI) tract (gastric, esophageal, and gastroesophageal) adenocarcinomas. The purpose of this review is to provide pathologists with practical guidance in HER2 assessment of upper GI tract adenocarcinomas in order to accurately identify patients eligible for trastuzumab therapy. PMID- 26839095 TI - Lymphomas of the Gastrointestinal Tract: An Update. AB - The gastrointestinal tract is the most common extranodal site of non-Hodgkin lymphoma. Certain lymphomas have a predilection for the gastrointestinal tract, including extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, mantle cell lymphoma, natural killer/T-cell lymphoma, and enteropathy-associated T-cell lymphoma. Follicular lymphoma may also be primary to the gastrointestinal tract. In addition to diagnosing neoplastic conditions, it is important to differentiate lymphomas from atypical reactive proliferations. Recent research relevant to non-Hodgkin lymphomas involving this location is reviewed with an emphasis on novel and evolving areas of classification. PMID- 26839093 TI - Management of hereditary medullary thyroid carcinoma. AB - Hereditary medullary thyroid carcinoma (MTC) represents up to one-third of MTC cases and includes multiple endocrine neoplasia syndrome type 2A (and its variant familial MTC) and 2B. The aim of this paper is to provide an overview of the disease focusing on the management of hereditary MTC patients, who have already developed tumor, as well as discuss the recommended approach for asymptomatic family members carrying the same mutation. A PubMed search was performed to review recent literature on diagnosis, genetic testing, and surgical and medical management of hereditary MTC. The wide use of genetic testing for RET mutations has markedly influenced the course of hereditary MTC. Prophylactic thyroidectomy of RET carriers at an early age eliminates the risk of developing MTC later in life. Pre-operative staging is a strong prognostic factor in patients, who have developed MTC. The use of recently approved tyrosine kinase inhibitors (vandetanib, cabozantinib) holds promising results for the treatment of unresectable, locally advanced, and progressive metastatic MTC. Genetic testing of the RET gene is a powerful tool in the diagnosis and prognosis of MTC. Ongoing research is expected to add novel treatment options for patients with advanced, progressive disease. PMID- 26839096 TI - Mesenchymal Tumors of the Gastrointestinal Tract Other than GIST. AB - Mesenchymal tumors involve the gastrointestinal (GI) tract more frequently than other visceral organs. Many such tumors are small, and are benign and increasingly being detected incidentally during colonoscopic screening. Some tumors show distinctive features at this site, such as schwannoma and clear cell sarcoma-like tumor of the GI tract. Without knowledge of these features, recognition of these tumor types can be difficult. This reviews addresses recent developments and diagnostic features of mesenchymal tumors of the GI tract other than gastrointestinal stromal tumor (GIST). PMID- 26839097 TI - Barrett Esophagus: Evolving Concepts in Diagnosis and Neoplastic Progression. AB - Surgical pathologists need to answer 2 questions when evaluating biopsies from the distal esophagus or gastroesophageal junction in patients with a history of gastroesophageal reflux disease: Are the findings consistent with Barrett esophagus? and Is there any evidence of dysplasia? Pathologists should be well informed about the controversy around the definition of Barrett esophagus and the common pitfalls that lead to a false-positive diagnosis of Barrett esophagus or Barrett esophagus-associated dysplasia. A concise description of distinct morphologic types of dysplasia in Barrett esophagus and a summary of recent data on the natural history of BE are provided in this review. PMID- 26839098 TI - IgG4-related Disorders of the Gastrointestinal Tract. AB - IgG4-related disease, a newly established multisystemic disease can affect virtually every organ. Histologically, it is characterized by the presence of a dense lymphoplasmacytic infiltrate, storiform-type fibrosis, and obliterative phlebitis. The disease shows elevated serum and tissue IgG4. The pancreas and hepatobiliary tract are involved far more commonly than the tubular gut. This review summarizes the clinical and pathologic features of the gastrointestinal manifestations of IgG4-related disease and discusses the wide spectrum of diseases that this entity may mimic. PMID- 26839099 TI - Diarrheal Illness in the Pediatric Population: A Review of Neonatal Enteropathies and Childhood Idiopathic Inflammatory Bowel Disease. AB - In the clinical context of pediatric diarrheal illness, the interpretation of endoscopic mucosal biopsies varies significantly from that in adults. This review outlines these differences by first describing a host of diarrheal illnesses that are nearly exclusive to the pediatric age group. The final portion of this article describes salient pathologic differences between adult and pediatric idiopathic inflammatory bowel disease. The goal of this review is to provide a brief description of each disease process and focus on practical aspects of diagnosis that are applicable for pathologists working in general practice settings. PMID- 26839100 TI - Polyposis Syndromes: Role of the Pathologist. AB - This article reviews the major gastrointestinal polyposis syndromes, with an emphasis on the molecular, clinical, and histopathological features of each. Salient features helpful in making or suggesting the diagnosis of these syndromes are discussed, as is the use of ancillary techniques, such as immunohistochemistry and molecular diagnostic studies in diagnosis confirmation and family screening. PMID- 26839101 TI - Immunohistochemistry in Gastroenterohepatopancreatobiliary Epithelial Neoplasia: Practical Applications, Pitfalls, and Emerging Markers. AB - Immunohistochemistry (IHC) has broad applications in neoplastic gastrointestinal surgical pathology. Although classically used as a diagnostic tool, IHC increasingly provides prognostic and predictive information. This review highlights 11 key uses of IHC (Box 1). Emphasis is placed on specific clinical applications and qualitative aspects of interpretation. Common pitfalls are specifically highlighted. The potential application of emerging markers is discussed in relation to several of the 11 topics. In many instances, an immunostain serves as a surrogate for specific molecular genetic events. Survey of relevant articles forms the evidence basis for this review. PMID- 26839104 TI - Current Concepts in Gastrointestinal Pathology: Classification, Diagnosis, Emerging Entities. PMID- 26839107 TI - Influenza Vaccination Coverage Rate for Medical Staff: Influence of Hospital Based Vaccination Campaign. AB - Despite intensive recommendations, influenza vaccination rate in medical staff in Poland ranges from about 20 % in physicians to 10 % in nurses. The objective of this work was to assess the influence of hospital influenza vaccination campaign directed toward health care workers, combined with dispensing free of charge vaccine, on vaccination rate. The campaign was conducted by the Hospital Infection Control Team of the Czerniakowski Hospital in Warsaw, Poland, separately for physicians, nurses, and physiotherapists. Overall, 37 % of medical staff were vaccinated, including 55 % of physicians and 21 % of nurses. Concerning physicians, the greatest vaccination rate was in the orthopedic (80 %) and ophthalmology units (73 %), whereas the lowest rate was in the intensive care (22 %) and neurology units (20 %). Concerning nurses, the greatest vaccination rate was in those working in the outpatient (40 %) and emergency units (29 %), whereas the lowest rate was in the ophthalmology (6 %) and surgery units (11 %). We conclude that the professional knowledge campaign combined with the incentive of free of charge vaccine substantially raises the vaccination rate among medical staff. PMID- 26839108 TI - Peer Support and Outcome for Veterans with Posttraumatic Stress Disorder (PTSD) in a Residential Rehabilitation Program. AB - This observational study aims to determine the characteristics of peer support that change attitudes toward recovery and PTSD symptom severity. The study respondents were a sample of 55 VA patients who were residents at a residential rehabilitation program for PTSD where they were the recipients of peer support. Veterans perceived greater support from other veterans (mean = 4.04 on 1-5 scale, SD = 0.78) than from any other source. Greater perceived support from the peer support provider, other veterans and mental health staff was associated with improvements from intake to discharge in recovery attitudes. Greater perceived support from other veterans and mental health staff was associated with an improvement in PTSD symptoms. Results from this study suggest that positive perceptions of peer support favorably influences attitudes toward recovery, from PTSD, in veterans who are the recipients of such support. PMID- 26839110 TI - Trocar Injuries in 17,446 Laparoscopic Gastric Bypass-a Nationwide Survey from the Scandinavian Obesity Surgery Registry. AB - BACKGROUND: Although, the vast majority of bariatric procedures worldwide are performed laparoscopically, there is no consensus on the best technique to enter the first trocar, a potentially dangerous maneuver. Three principally different techniques exist: initial pneumoperitoneum by Verres needle, open Hasson technique, and direct placement of an optical trocar. In this nationwide survey, we have studied the presently used technique to place the first trocar and identified any intraabdominal injuries in 2012-2014. METHODS: A questionnaire concerning techniques for placing the first trocar and identified intraabdominal injuries was sent to all 41 centers performing laparoscopic Roux en-Y gastric bypass (LRYGB) in Sweden. Total number of procedures were collected from the national quality registry, Scandinavian Obesity Surgery Registry (SOReg), also searched for reports on intraabdominal injuries. RESULTS: During the present study period, 17,446 LRYGBs were performed. Twelve intraabdominal injuries (0.07 %) were found: bleedings from the omentum, small bowel mesentery and liver (n = 8), and gastric or small bowel perforation (n = 4). The injuries were evenly distributed between the Veress technique and direct placement of an optical trocar, while no injuries occurred with the Hasson technique. Concerning placement of the first trocar, initial pneumoperitoneum with Veress needle was most common (59 %), followed by direct placement of an optical trocar (30 %). This indicates a switch from 2009-2010 (Veress 45 % and optical trocar 45 %, p < 0.001). CONCLUSIONS: Twelve intraabdominal injuries (0.07 %) were found in this nationwide survey. The most common technique for placing the first trocar had switched from directly placing an optical trocar to prior establishment of pneumoperitoneum. PMID- 26839111 TI - Commentary on: Efficacy, Security, and Manageability of Gelified Hemostatic Matrix in Bleeding Control during Thoracic and Lumbar Spine Surgery: FloSeal vs Surgiflo. PMID- 26839109 TI - Oxidative stress and premature senescence in corneal endothelium following penetrating keratoplasty in an animal model. AB - BACKGROUND: The purpose of this study was to address the question of how the premature senescence process may affect corneal endothelium after penetrating keratoplasty, because the quality of donor corneal endothelial cells is important for corneal transplant success. METHODS: The cell senescence and induced oxidative stress in corneal endothelium were assessed using a normal-risk orthotopic mice corneal transplantation model. Senescence associated beta galactosidase (SA-beta-Gal) staining was used to evaluate premature senescence in the endothelium of corneal allografts. Oxidative Stress and Antioxidant Defense RT(2)-PCR Arrays and in vitro experimental model using H2O2 treatment were used to investigate the possible mechanism. RESULTS: SA-beta-Gal positivity was observed obviously in mice corneal endothelium of allogenic group and the levels of p16(INK4a) message and protein increased in endothelium of allogenic group compared to syngenic group. By PCR array, an oxidant-antioxidant imbalance was found in the endothelium of corneal allograft after PKP. The results from mice model were validated using human endothelium samples of corneal allograft after PKP. We also developed an in vitro experimental model using H2O2 treatment to simulate a state of oxidative stress in cultured human corneal endothelial cells (HCECs) and found that elevated ROS levels, the up-regulation of CDK inhibitors and ROS-mediated p16(INK4A) up-regulation in HCECs occur via the ASK1-p38 MAPK pathway. CONCLUSIONS: Our results demonstrate the presence of oxidative stress and premature senescence in the endothelium of corneal allografts following PKP. PMID- 26839112 TI - Phenotypic subregions within the split-hand/foot malformation 1 locus. AB - Split-hand/foot malformation 1 (SHFM1) is caused by chromosomal aberrations involving the region 7q21.3, DLX5 mutation, and dysregulation of DLX5/DLX6 expression by long-range position effects. SHFM1 can be isolated or syndromic with incomplete penetrance and a highly variable clinical expression, possibly influenced by sex and imprinting. We report on a new family with five affected individuals with syndromic SHFM1 that includes split-hand/foot malformations, hearing loss, and craniofacial anomalies, and an inv(7)(q21.3q35) present both in the proband and her affected son. The proximal inversion breakpoint, identified by next generation mate-pair sequencing, truncates the SHFM1 locus within the regulatory region of DLX5/6 expression. Through genotype-phenotype correlations of 100 patients with molecularly characterized chromosomal aberrations from 32 SHFM1 families, our findings suggest three phenotypic subregions within the SHFM1 locus associated with (1) isolated SHFM, (2) SHFM and hearing loss, and (3) SHFM, hearing loss, and craniofacial anomalies, respectively (ranked for increasing proximity to DLX5/6), and encompassing previously reported tissue-specific enhancers for DLX5/6. This uniquely well-characterized cohort of SHFM1 patients allowed us to systematically analyze the recently suggested hypothesis of skewed transmission and to confirm a higher penetrance in males vs. females in a subgroup of patients with isolated SHFM. PMID- 26839114 TI - Challenging the principle of proportionality. AB - The first objective of this article is to examine one aspect of the principle of proportionality (PP) as advanced by Alan Gewirth in his 1978 bookReason and Morality Gewirth claims that being capable of exercising agency to some minimal degree is a property that justifies having at least prima facie rights not to get killed. However, according to the PP, before the being possesses the capacity for exercising agency to that minimal degree, the extent of her rights depends on to what extent she approaches possession of agential capacities. One interpretation of PP holds that variations in degree of possession of the physical constitution necessary to exercise agency are morally relevant. The other interpretation holds that only variations in degree of actual mental capacity are morally relevant. The first of these interpretations is vastly more problematic than the other. The second objective is to argue that according to the most plausible interpretation of the PP, the fetus' level of development before at least the 20th week of pregnancy does not affect the fetus' moral rights status. I then suggest that my argument is not restricted to such fetuses, although extending my argument to more developed fetuses requires caution. PMID- 26839115 TI - Establishment of Functional Genomics Pipeline in Mouse Epiblast-Like Tissue by Combining Transcriptomic Analysis and Gene Knockdown/Knockin/Knockout, Using RNA Interference and CRISPR/Cas9. AB - The epiblast (foremost embryonic ectoderm) generates all three germ layers and therefore has crucial roles in the formation of all mammalian body cells. However, regulation of epiblast gene expression is poorly understood because of the difficulty of manipulating epiblast tissues in vivo. In the present study, using the self-organizing properties of mouse embryonic stem cell (ESC), we generated and characterized epiblast-like tissue in three-dimensional culture. We identified significant genome-wide gene expression changes in this epiblast-like tissue by transcriptomic analysis. In addition, we identified the particular significance of the Erk/Mapk and integrin-linked kinase pathways, and genes related to ectoderm/epithelial formation, using the bioinformatics resources IPA and DAVID. Here, we focused on Fgf5, which ranked in the top 10 among the discovered genes. To develop a functional analysis of Fgf5, we created an efficient method combining CRISPR/Cas9-mediated genome engineering and RNA interference (RNAi). Notably, we show one-step generation of various Fgf5 reporter lines including heterozygous and homozygous knockins (the GET method). For time- and dose-dependent depletion of fgf5 over the course of development, we generated an ESC line harboring Tol2 transposon-mediated integration of an inducible short hairpin RNA interference system (pdiRNAi). Our findings raised the possibility that Fgf/Erk signaling and apicobasal epithelial integrity are important factors in epiblast development. In addition, our methods provide a framework for a broad array of applications in the areas of mammalian genetics and molecular biology to understand development and to improve future therapeutics. PMID- 26839113 TI - Improved prediction of complex diseases by common genetic markers: state of the art and further perspectives. AB - Reliable risk assessment of frequent, but treatable diseases and disorders has considerable clinical and socio-economic relevance. However, as these conditions usually originate from a complex interplay between genetic and environmental factors, precise prediction remains a considerable challenge. The current progress in genotyping technology has resulted in a substantial increase of knowledge regarding the genetic basis of such diseases and disorders. Consequently, common genetic risk variants are increasingly being included in epidemiological models to improve risk prediction. This work reviews recent high quality publications targeting the prediction of common complex diseases. To be included in this review, articles had to report both, numerical measures of prediction performance based on traditional (non-genetic) risk factors, as well as measures of prediction performance when adding common genetic variants to the model. Systematic PubMed-based search finally identified 55 eligible studies. These studies were compared with respect to the chosen approach and methodology as well as results and clinical impact. Phenotypes analysed included tumours, diabetes mellitus, and cardiovascular diseases. All studies applied one or more statistical measures reporting on calibration, discrimination, or reclassification to quantify the benefit of including SNPs, but differed substantially regarding the methodological details that were reported. Several examples for improved risk assessments by considering disease-related SNPs were identified. Although the add-on benefit of including SNP genotyping data was mostly moderate, the strategy can be of clinical relevance and may, when being paralleled by an even deeper understanding of disease-related genetics, further explain the development of enhanced predictive and diagnostic strategies for complex diseases. PMID- 26839116 TI - Interventions for preventing unintended pregnancies among adolescents. AB - BACKGROUND: Unintended pregnancy among adolescents represents an important public health challenge in high-income countries, as well as middle- and low-income countries. Numerous prevention strategies such as health education, skills building and improving accessibility to contraceptives have been employed by countries across the world, in an effort to address this problem. However, there is uncertainty regarding the effects of these interventions, hence the need to review the evidence-base. OBJECTIVES: To assess the effects of primary prevention interventions (school-based, community/home-based, clinic-based, and faith-based) on unintended pregnancies among adolescents. SEARCH METHODS: We searched all relevant studies regardless of language or publication status up to November 2015. We searched the Cochrane Fertility Regulation Group Specialised trial register, The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2015 Issue 11), MEDLINE, EMBASE, LILACS, Social Science Citation Index and Science Citation Index, Dissertations Abstracts Online, The Gray Literature Network, HealthStar, PsycINFO, CINAHL and POPLINE and the reference lists of articles. SELECTION CRITERIA: We included both individual and cluster randomised controlled trials (RCTs) evaluating any interventions that aimed to increase knowledge and attitudes relating to risk of unintended pregnancies, promote delay in the initiation of sexual intercourse and encourage consistent use of birth control methods to reduce unintended pregnancies in adolescents aged 10 years to 19 years. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and risk of bias, and extracted data. Where appropriate, binary outcomes were pooled using a random-effects model with a 95% confidence interval (Cl). Where appropriate, we combined data in meta-analyses and assessed the quality of the evidence using the GRADE approach. MAIN RESULTS: We included 53 RCTs that enrolled 105,368 adolescents. Participants were ethnically diverse. Eighteen studies randomised individuals, 32 randomised clusters (schools (20), classrooms (6), and communities/neighbourhoods (6). Three studies were mixed (individually and cluster randomised). The length of follow up varied from three months to seven years with more than 12 months being the most common duration. Four trials were conducted in low- and middle- income countries, and all others were conducted in high-income countries. Multiple interventionsResults showed that multiple interventions (combination of educational and contraceptive-promoting interventions) lowered the risk of unintended pregnancy among adolescents significantly (RR 0.66, 95% CI 0.50 to 0.87; 4 individual RCTs, 1905 participants, moderate quality evidence. However, this reduction was not statistically significant from cluster RCTs. Evidence on the possible effects of interventions on secondary outcomes (initiation of sexual intercourse, use of birth control methods, abortion, childbirth, sexually transmitted diseases) was not conclusive.Methodological strengths included a relatively large sample size and statistical control for baseline differences, while limitations included lack of biological outcomes, possible self-report bias, analysis neglecting clustered randomisation and the use of different statistical tests in reporting outcomes. Educational interventionsEducational interventions were unlikely to significantly delay the initiation of sexual intercourse among adolescents compared to controls (RR 0.95, 95% CI 0.71 to 1.27; 2 studies, 672 participants, low quality evidence).Educational interventions significantly increased reported condom use at last sex in adolescents compared to controls who did not receive the intervention (RR 1.18, 95% CI 1.06 to 1.32; 2 studies, 1431 participants, moderate quality evidence).However, it is not clear if the educational interventions had any effect on unintended pregnancy as this was not reported by any of the included studies. Contraceptive-promoting interventionsFor adolescents who received contraceptive-promoting interventions, there was little or no difference in the risk of unintended first pregnancy compared to controls (RR 1.01, 95% CI 0.81 to 1.26; 2 studies, 3,440 participants, moderate quality evidence).The use of hormonal contraceptives was significantly higher in adolescents in the intervention group compared to those in the control group (RR 2.22, 95% CI 1.07 to 4.62; 2 studies, 3,091 participants, high quality evidence) AUTHORS' CONCLUSIONS: A combination of educational and contraceptive-promoting interventions appears to reduce unintended pregnancy among adolescents. Evidence for programme effects on biological measures is limited. The variability in study populations, interventions and outcomes of included trials, and the paucity of studies directly comparing different interventions preclude a definitive conclusion regarding which type of intervention is most effective. PMID- 26839117 TI - [Urology and Sexology in Berlin 1880-1933: Original citations for the establishment of this frontier of urology - protagonists as reflected in their publications]. AB - The connections between urology and sexology are often not obvious today. At the end of the 19th century both specialties developed in parallel especially in Berlin and had a fruitful relationship. Urologic journals and books were an ideal forum for publication especially for sexologists. PMID- 26839121 TI - Experiences and reflections of patients with motor neuron disease on breaking the news in a two-tiered appointment: a qualitative study. AB - BACKGROUND: Breaking bad news should be fine-tuned to the individual patient, contain intelligible information, include emotional support and offer a tailor made treatment plan. To achieve this goal in motor neuron disease (MND), neurologists of the amyotrophic lateral sclerosis (ALS) centre Amsterdam deliver the message on 2 separate visits within 14 days. AIM: To evaluate how patients with MND react to and view disclosure of the diagnosis, in this 2-tiered approach. METHODS: Non-participating observations and in-depth interviews with patients were conducted in 1 tertiary ALS referral centre. Qualitative analysis consisted of inductive analysis of observation reports and verbatim typed out interviews. RESULTS: 10 2-tiered appointments were observed and 21 Dutch patients with MND interviewed. They experienced the straightforward message to be suffering from a fatal disease as devastating, yet unavoidable. The prospect of a short-term second appointment offered structure for the period immediately following the diagnosis. The time between appointments provided the opportunity for a first reorientation on their changed perspective on their life. The second appointment allowed for detailed discussions about various aspects of MND and a tailor-made treatment plan. CONCLUSIONS: The 2-tiered approach fits well with the way in which Dutch patients with MND process the disclosure of their diagnosis, gather information and handle the changed perspective on their life. It may serve as a model for other life-limiting diseases. PMID- 26839122 TI - Retraction Note: RGD peptide-pegylated PLLA nanoparticles containing epirubicin hydrochloride exhibit receptor-dependent tumor trafficking in vitro and in vivo. PMID- 26839120 TI - Presence of retinal pericyte-reactive autoantibodies in diabetic retinopathy patients. AB - The loss of retinal pericytes (RPCs) is a hallmark of early stage diabetic retinopathy (DR), but the mechanism underlying RPC death is unclear. Although it was postulated in previous studies using bovine RPCs that autoantibodies against RPCs might develop and induce RPC death, it is unknown whether autoantibodies against cell-surface antigens on human RPCs exist in DR patients, whether such autoantibodies contribute to RPC damage/loss, and if they do, through which mechanism. We screened serum samples from DR patients and controls using primary human RPCs and found that that levels of IgGs reactive to RPCs were significantly higher in the DR group than the control group. Serum samples with higher RPC reactive IgG levels induced more severe complement-mediated RPC damage than those with lower RPC-reactive IgG levels. We also assessed levels of the complement activation products C3a, C4a and C5a in these serum samples, and found that serum levels of C3a and C5a, but not C4a, were higher in the DR group than control group. These data provide evidence the first time showing that autoantibodies against RPCs can develop in DR patients, and that these autoantibodies could contribute to pericyte damage through complement activation. PMID- 26839124 TI - A Microscopic and Biomarker Evaluation of Embolic Filter Debris Collected During Carotid Artery Stenting. AB - PURPOSE: To evaluate and characterize debris retrieved from the cerebral embolic protection devices (EPDs) used during carotid artery stenting (CAS) and compare debris size, volume, tissue types, cellular composition, and protein biomarker expression in symptomatic and asymptomatic patients. METHODS: Distal protection filters were retrieved from 22 consecutive patients (mean age 71.6 years, range 52-85; 16 men) undergoing elective CAS between July 2012 and February 2014 for >70% internal carotid artery stenosis (mean 85.4% +/- 10.3%). Six patients were symptomatic. The debris within each EPD was visually characterized using stereomicroscopy and then processed for histology and immunohistochemistry. Biomarkers were immunohistochemically measured to evaluate plaque stability [matrix metalloproteinase-9 (MMP-9)], inflammation [glycoprotein CD68 and interleukin-6 (IL-6)], or phenotype [smooth muscle (SM)-actin and type IV collagen]. The immunohistochemical results were measured using semiquantitative grading criteria based on both staining intensity and distribution in the samples. RESULTS: Macroscopic debris was visible in 5/22 EPDs; 3 of the 5 filters came from symptomatic patients. Microscopic debris was detected in all filters and ranged in size from 0.01 to 8.57 mm(2). Debris consisted of calcified, fibrous, and necrotic tissue, as well as fibrin and foam cells with no significant difference between the symptomatic and asymptomatic groups. There was no association between the degree or type of embolic material and stenosis severity, carotid tortuosity, calcium grade, soft plaque, or arch type. Symptomatic patients had a larger volume of debris (8.24 vs 0.58 mm(3), p<0.01), mean particle size (1.30 vs 0.32 mm(2), p<0.001), and expression of biomarkers IL 6 (2.17 vs 0.81, p<0.05), CD68 (2.00 vs 0.38, p<0.01), SM-actin (1.00 vs 0.25, p=0.055), type IV collagen (1.17 vs 0.25,p=0.082), and MMP-9 (1.00 vs 0.06, p<0.05). CONCLUSION: Histological analysis revealed particulate embolization in all EPDs used during CAS. Symptomatic patients had a larger volume of embolic debris, mean particle size, and the biomarkers associated with inflammation, necrotic core, and diminished fibrous cap. PMID- 26839123 TI - Semantic and emotional content of imagined representations in human occipitotemporal cortex. AB - Mental imagery is a critical cognitive function, clinically important, but poorly understood. When visual objects are perceived, many of their sensory, semantic and emotional properties are represented in occipitotemporal cortex. Visual imagery has been found to activate some of the same brain regions, but it was not known what properties are re-created in these regions during imagery. We therefore examined the representation during imagery for two stimuli in depth, by comparing the pattern of fMRI response to the patterns evoked by the perception of 200 diverse objects chosen to de-correlate their properties. Real-time, adaptive stimulus selection allowed efficient sampling of this broad stimulus space. Our experiments show that occipitotemporal cortex, which encoded sensory, semantic and emotional properties during perception, can robustly represent semantic and emotional properties during imagery, but that these representations depend on the object being imagined and on individual differences in style and reported vividness of imagery. PMID- 26839125 TI - Learning Motivational Interviewing: A Pathway to Caring and Mindful Patient Encounters. AB - We designed our project to explore the experience of learning motivational interviewing (MI). The project impetus came from a desire to improve our skill in communicating with patients. We created a curriculum led by an MI specialist that provided didactic sessions, discussions and individual feedback. In evaluating our audio-taped MI encounters, we approached beginner proficiency. Also, we recognized the need for formal MI education and practice to fully develop the interventionist skills needed for clinical work and our next research project about preparing patients for transition to adult health care. Lastly, we realized that MI strategies reflect aspects of caring theory and mindfulness, important components of patient-centered care. PMID- 26839126 TI - Preparation and application of conducting polymer/Ag/clay composite nanoparticles formed by in situ UV-induced dispersion polymerization. AB - In this work, composite nanoparticles containing polypyrrole, silver and attapulgite (PPy/Ag/ATP) were prepared via UV-induced dispersion polymerization of pyrrole using ATP clay as a templet and silver nitrate as photoinitiator. The effects of ATP concentration on morphology, structure and electrical conductivity were studied. The obtained composite nanoparticles with an interesting beads-on-a string morphology can be obtained in a short time (10 min), which indicates the preparation method is facile and feasible. To explore the potential applications of the prepared PPy/Ag/ATP composite nanoparticles, they were served as multifunctional filler and blended with poly(butylene succinate) (PBS) matrix to prepare biodegradable composite material. The distribution of fillers in polymer matrix and the interfacial interaction between fillers and PBS were confirmed by scanning electron microscope, elemental mapping and dynamic mechanical analysis. The well dispersed fillers in PBS matrix impart outstanding antibacterial property to the biodegradable composite material as well as enhanced storage modulus due to Ag nanoparticles and ATP clay. The biodegradable composite material also possesses modest surface resistivity (10(6)~ 10(9) Omega/?). PMID- 26839127 TI - PUB1 Interacts with the Receptor Kinase DMI2 and Negatively Regulates Rhizobial and Arbuscular Mycorrhizal Symbioses through Its Ubiquitination Activity in Medicago truncatula. AB - PUB1, an E3 ubiquitin ligase, which interacts with and is phosphorylated by the LYK3 symbiotic receptor kinase, negatively regulates rhizobial infection and nodulation during the nitrogen-fixing root nodule symbiosis in Medicago truncatula In this study, we show that PUB1 also interacts with and is phosphorylated by DOES NOT MAKE INFECTIONS 2, the key symbiotic receptor kinase of the common symbiosis signaling pathway, required for both the rhizobial and the arbuscular mycorrhizal (AM) endosymbioses. We also show here that PUB1 expression is activated during successive stages of root colonization by Rhizophagus irregularis that is compatible with its interaction with DOES NOT MAKE INFECTIONS 2. Through characterization of a mutant, pub1-1, affected by the E3 ubiquitin ligase activity of PUB1, we have shown that the ubiquitination activity of PUB1 is required to negatively modulate successive stages of infection and development of rhizobial and AM symbioses. In conclusion, PUB1 represents, to our knowledge, a novel common component of symbiotic signaling integrating signal perception through interaction with and phosphorylation by two key symbiotic receptor kinases, and downstream signaling via its ubiquitination activity to fine-tune both rhizobial and AM root endosymbioses. PMID- 26839130 TI - Serrated Colorectal Neoplasia. AB - Until very recently, there was general acceptance in the pathology community that all serrated lesions of the colon and rectum without overt cytologic dysplasia were hyperplastic polyps and had no malignant potential. Although there are still several unanswered questions in regard to the relationship between the various serrated lesions, there is a better understanding of the relationship of sessile serrated adenoma to carcinoma. This article discusses hyperplastic polyps, sessile serrated adenoma, traditional serrated adenoma, mixed polyps, and serrated lesions in such conditions as idiopathic inflammatory bowel disease and mechanical trauma. The major focus of the content is on diagnostic features of these lesions. PMID- 26839128 TI - Large-Scale Analyses of Angiosperm Nucleotide-Binding Site-Leucine-Rich Repeat Genes Reveal Three Anciently Diverged Classes with Distinct Evolutionary Patterns. AB - Nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes make up the largest plant disease resistance gene family (R genes), with hundreds of copies occurring in individual angiosperm genomes. However, the expansion history of NBS-LRR genes during angiosperm evolution is largely unknown. By identifying more than 6,000 NBS-LRR genes in 22 representative angiosperms and reconstructing their phylogenies, we present a potential framework of NBS-LRR gene evolution in the angiosperm. Three anciently diverged NBS-LRR classes (TNLs, CNLs, and RNLs) were distinguished with unique exon-intron structures and DNA motif sequences. A total of seven ancient TNL, 14 CNL, and two RNL lineages were discovered in the ancestral angiosperm, from which all current NBS-LRR gene repertoires were evolved. A pattern of gradual expansion during the first 100 million years of evolution of the angiosperm clade was observed for CNLs. TNL numbers remained stable during this period but were eventually deleted in three divergent angiosperm lineages. We inferred that an intense expansion of both TNL and CNL genes started from the Cretaceous-Paleogene boundary. Because dramatic environmental changes and an explosion in fungal diversity occurred during this period, the observed expansions of R genes probably reflect convergent adaptive responses of various angiosperm families. An ancient whole-genome duplication event that occurred in an angiosperm ancestor resulted in two RNL lineages, which were conservatively evolved and acted as scaffold proteins for defense signal transduction. Overall, the reconstructed framework of angiosperm NBS-LRR gene evolution in this study may serve as a fundamental reference for better understanding angiosperm NBS-LRR genes. PMID- 26839131 TI - Gastrointestinal Stromal Tumors: A Guide to the Diagnosis. AB - Gastrointestinal stromal tumors (GISTs) have emerged from being a poorly understood and therapeutically refractory sarcoma to a tumor whose biology has not only provided insight into a mechanism of oncogenesis but has also led to a rational basis for therapy. Most GISTs are characterized by KIT protein (CD117) expression and constitutive activating mutations in either the c-kit or platelet derived growth factor receptor alpha genes. This information can now be obtained from routine formalin-fixed and paraffin-embedded tissue. Because the correct diagnosis is the key to successful treatment of this tumor, it is incumbent on the pathologist to be familiar with the various gross and histologic patterns shown by these tumors. GISTs range from small incidental stromal nodules to large cystic and solid tumor masses. GISTs show a variety of microscopic patterns and therefore several other tumors enter the differential diagnosis. Fortunately, with an understanding of GIST histology, and with the proper use of immunohistochemistry and molecular analysis, a correct diagnosis can usually be made. In addition to the correct diagnosis, several key attributes of the tumor need to be determined because they provide the basis for proper clinical management. This article summarizes the gross, microscopic, and molecular findings of GISTs, and discusses the differential diagnosis and key attributes of this interesting group of neoplasms. PMID- 26839129 TI - WHITE PANICLE1, a Val-tRNA Synthetase Regulating Chloroplast Ribosome Biogenesis in Rice, Is Essential for Early Chloroplast Development. AB - Chloroplasts and mitochondria contain their own genomes and transcriptional and translational systems. Establishing these genetic systems is essential for plant growth and development. Here we characterized a mutant form of a Val-tRNA synthetase (OsValRS2) from Oryza sativa that is targeted to both chloroplasts and mitochondria. A single base change in OsValRS2 caused virescent to albino phenotypes in seedlings and white panicles at heading. We therefore named this mutant white panicle 1 (wp1). Chlorophyll autofluorescence observations and transmission electron microscopy analyses indicated that wp1 mutants are defective in early chloroplast development. RNA-seq analysis revealed that expression of nuclear-encoded photosynthetic genes is significantly repressed, while expression of many chloroplast-encoded genes also changed significantly in wp1 mutants. Western-blot analyses of chloroplast-encoded proteins showed that chloroplast protein levels were reduced in wp1 mutants, although mRNA levels of some genes were higher in wp1 than in wild type. We found that wp1 was impaired in chloroplast ribosome biogenesis. Taken together, our results show that OsValRS2 plays an essential role in chloroplast development and regulating chloroplast ribosome biogenesis. PMID- 26839132 TI - Esophageal Eosinophilia. AB - The presence of esophageal eosinophilia encompasses a broad differential diagnosis, and at times a specific histologic diagnosis is not possible. This content provides a systematic approach to esophageal squamous eosinophilia with emphasis on specific, distinguishing features within this expansive differential. PMID- 26839133 TI - Infectious Diseases of the Lower Gastrointestinal Tract. AB - Gastrointestinal (GI) infections are a major cause of morbidity and mortality worldwide. Although infectious organisms are often recovered by microbiological methods, surgical pathologists play an invaluable role in diagnosis. The lower GI tract, including the appendix, large bowel, and anus, harbors a wide variety of pathogens. Some infections are part of disseminated disease, whereas others produce clinicopathologic scenarios that are specific to the lower GI tract. This review focuses on selected infectious disorders of the lower GI tract that may be encountered by the general surgical pathologist, including viral, bacterial, fungal, and parasitic organisms, and including infections caused by food- and water-borne pathogens. Diagnostic gross and histologic features are discussed, as well as useful clinical features and ancillary diagnostic techniques. Pertinent differential diagnoses are also emphasized, including other inflammatory conditions of the gut (such as ischemia or idiopathic inflammatory bowel disease) that can be mimicked by lower GI infections. PMID- 26839134 TI - Pathology of Gastrointestinal Neuroendocrine Tumors: An Update. AB - Gastrointestinal (GI) neuroendocrine tumors (NETs) are a heterogeneous group of relatively slow-growing neoplasms with marked site-specific differences in hormonal secretion and clinical behavior. Most are sporadic neoplasms, with only 5% to 10% arising in patients with hereditary disorders, most commonly in multiple endocrine neoplasia type 1. Although a uniform terminology is not universally accepted, use of the 4-category WHO classification of these tumors is becoming more widespread, and recommendations for tumor grading and staging have been recently formulated. Most GI NETs are easily recognized on routine histologic examination; rarely, a limited panel of immunohistochemical markers may be useful in establishing the diagnosis. This article describes general and site-specific features of these tumors and outlines potential pitfalls in diagnosis. PMID- 26839135 TI - Upper Gastrointestinal Tract in Inflammatory Bowel Disease. AB - Involvement of the upper gastrointestinal tract by inflammatory bowel disease was long held to be a feature of Crohn's disease, whereas ulcerative colitis was considered to be limited to the colon. It is now recognized that ulcerative colitis associated inflammation can involve the upper gastrointestinal tract, primarily the stomach. In addition to aphthoid esophageal ulcers in Crohn's disease, eosinophilic esophagitis and so-called lymphocytic esophagitis occur in association with ulcerative colitis and Crohn's disease. Possible immune mechanisms behind these conditions are presented. The differential diagnosis of inflammation in each site is discussed. PMID- 26839136 TI - Drug-induced Injury of the Gastrointestinal Tract. AB - The effects of drugs on the gastrointestinal tract are diverse and depend on numerous factors. Diagnosis is centered on histologic findings, with mostly nonspecific patterns of injury that must be interpreted in the correct clinical context. Nonsteroidal antiinflammatory drugs are a common cause of drug-induced gastrointestinal injury, with effects primarily in the gastric mucosa but also throughout the gastrointestinal tract. Another common class of drugs causing a variety of pathologic findings in the gut is chemotherapeutic agents. This article discusses the differential diagnosis of the various patterns of injury, including ischemic damage, and the histologic findings specific for certain drugs. PMID- 26839137 TI - Mucinous Neoplasms of the Vermiform Appendix. AB - Most epithelial neoplasms of the vermiform appendix are of mucinous type and can be stratified into 3 main diagnostic categories: (1) adenoma, (2) mucinous neoplasms of uncertain malignant potential or low-grade mucinous neoplasm, and (3) adenocarcinoma. Clinically, appendiceal mucinous adenomas and adenocarcinomas may present as right lower abdominal pain mimicking acute appendicitis, a mass, or pseudomyxoma peritonei. Nomenclature currently in use to describe and diagnose mucinous tumors of the appendix, particularly those of low morphologic grade, varies among surgical pathologists and centers, resulting in different histologic and clinical features being attributed to these entities in the literature. It may be of help, as already attempted by some investigators, to simply apply algorithmic parameters for such lesions (grade of the primary lesion, extensiveness and composite of extra-appendiceal involvement, and so forth), instead of adopting rigid classification categories. This approach allows for more objective data to be collected in hopes that it will provide a more nuanced understanding of the clinical behavior of the spectrum of mucinous appendiceal tumors. Remaining focused on histopathologic parameters of the primary and secondary sites of involvement may help in avoiding circular reasoning. PMID- 26839138 TI - New Endoscopic Techniques: Challenges and Opportunities for Surgical Pathologists. AB - In recent years, significant clinical and technological advances have been made in endoscopic methods for diagnosis and treatment of early gastrointestinal neoplasms. However, essential information related to these novel techniques and their implications for practicing surgical pathologists have largely been missing in the general pathology literature. This article provides a general introduction to these novel therapeutic and diagnostic methods, and discusses their indications, contraindications, and potential limitations. The article aims to enable surgical pathologists to interact more efficiently with basic scientists and clinical colleagues to help implement and improve the existing clinical methods and to advance the new technologies. PMID- 26839139 TI - Molecular Testing in Colorectal Carcinoma. AB - An estimated 150,000 individuals are diagnosed with colorectal carcinoma (CRC) each year, and approximately 50,000 will die from this disease, making CRC the third leading cause of cancer deaths in the United States. For this reason, an enormous amount of effort has been spent to understand the molecular pathogenesis of this disease and to develop screening tests and prognostic markers. In the last 10 years, there has been a revolution in the understanding of CRC due to the identification of multiple distinct molecular pathways. With the introduction of biologic agents that target particular subtypes of CRC, molecular analysis of CRC is becoming standard of care in surgical pathology. In this context, the authors first describe the multiple molecular pathways leading to CRC and then discuss the role of molecular testing in the diagnosis of Lynch syndrome (formerly hereditary nonpolyposis colorectal carcinoma), prognosis, and therapy. PMID- 26839140 TI - Daily Challenges in GI Pathology. PMID- 26839141 TI - The role of radical prostatectomy in high-risk localized, node-positive and metastatic prostate cancer. AB - A lack of quality evidence comparing management strategies confounds complex treatment decisions for patients with high-risk prostate cancers. No randomized trial comparing surgery to radiation has been successfully completed. Despite inherent selection biases, however, observational and registry data suggest improved outcomes for patients initially managed with prostatectomy. As consensus shifts away from aggressive treatment for low-risk disease and toward multimodal treatment of locally advanced and metastatic disease, there is renewed interest in surgery for local control in patients presenting with high-risk localized, node-positive and minimally metastatic disease. The objective of this review is to examine the evidence evaluating clinical outcomes of patients with high-risk clinically localized, node-positive and metastatic prostate cancer treated with radical prostatectomy. PMID- 26839142 TI - Visible light photoredox-controlled reactions of N-radicals and radical ions. AB - Radicals are an important class of versatile and highly reactive species. Compared with the wide applications of various C-centred radicals, however, the N radical species including N-centred radicals and radical ions remain largely unexplored due to the lack of convenient methods for their generation. In recent years, visible light photoredox catalysis has emerged as a powerful platform for the generation of various N-radical species and methodology development towards the synthesis of diverse N-containing compounds. In this tutorial review, we highlight recent advances in this rapidly developing area with particular emphases put on the working models and new reaction design. PMID- 26839143 TI - Interpersonal interactions and empathy modulate perception of threat and defensive responses. AB - The defensive peripersonal space (DPPS) is a vital "safety margin" surrounding the body. When a threatening stimulus is delivered inside the DPPS, subcortical defensive responses like the hand-blink reflex (HBR) are adjusted depending on the perceived threat content. In three experiments, we explored whether and how defensive responses are affected by the interpersonal interaction within the DPPS of the face. In Experiment 1, we found that the HBR is enhanced when the threat is brought close to the face not only by one's own stimulated hand, but also by another person's hand, although to a significantly lesser extent. In Experiments 2 and 3, we found that the HBR is also enhanced when the hand of the participant enters the DPPS of another individual, either in egocentric or in allocentric perspective. This enhancement is larger in participants with strong empathic tendency when the other individual is in a third person perspective. These results indicate that interpersonal interactions shape perception of threat and defensive responses. These effects are particularly evident in individuals with greater tendency to having empathic concern to other people. PMID- 26839144 TI - Differential Effect on Bone Lesions of Targeting Integrins: Randomized Phase II Trial of Abituzumab in Patients with Metastatic Castration-Resistant Prostate Cancer. AB - PURPOSE: Integrins play a critical role in the progression of prostate cancer and its bone metastases. We investigated the use of the pan-alphav integrin inhibitor abituzumab in chemotherapy-naive patients with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer. EXPERIMENTAL DESIGN: PERSEUS (NCT01360840) was a randomized, double-blind phase II study. Men with pathologically confirmed prostate cancer and radiologic progression of bone lesions in the 28 days prior to randomization were assigned to receive abituzumab 750 mg or 1,500 mg or placebo (1:1:1) every 3 weeks in combination with luteinizing hormone-releasing hormone agonist/antagonist therapy. The primary endpoint was progression-free survival (PFS). RESULTS: The intent-to-treat population comprised 180 patients, 60 in each arm. The primary endpoint of PFS was not significantly different with abituzumab-based therapy compared with placebo [abituzumab 750 mg, 3.4 months, HR = 0.89; 95% confidence interval (CI), 0.57-1.39; abituzumab 1,500 mg, 4.3 months, HR = 0.81; 95% CI, 0.52-1.26; placebo, 3.3 months], but the cumulative incidence of bone lesion progression was lower with abituzumab than with placebo for up to 24 months (cumulative incidence 23.6% vs. 41.1% at 6 months, 26.1% vs. 45.4% at 12 months). Two partial tumor responses were observed (1 abituzumab 1,500 mg and 1 placebo). Approximately 85% to 90% of patients experienced at least one treatment-emergent adverse event (TEAE) in the different arms, but the incidences of serious TEAEs and TEAEs with fatal outcome were similar in the three arms. CONCLUSIONS: Although PFS was not significantly extended, abituzumab appears to have specific activity in prostate cancer-associated bone lesions that warrants further investigation. Clin Cancer Res; 22(13); 3192-200. (c)2016 AACR. PMID- 26839145 TI - Prognostic Impact of IL6 Genetic Variants in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab-Based Chemotherapy. AB - PURPOSE: The IL6/STAT3 axis promotes inflammation, angiogenesis, and cancer. The effect of genetic variants within this pathway on benefit from antiangiogenic cancer therapy is unknown. We tested whether SNPs in genes involved in IL6/STAT3 signaling can predict efficacy of bevacizumab-based chemotherapy in metastatic colorectal cancer (mCRC) patients. EXPERIMENTAL DESIGN: Associations between potentially functional IL6 (rs2069837 and rs1800795) and STAT3 (rs744166 and rs4796793) SNPs and clinical outcomes [progression-free survival (PFS), overall survival, and tumor response rate] were evaluated in mCRC patients receiving first-line FOLFIRI plus bevacizumab in two randomized phase III trials: TRIBE (n = 223, training cohort) and FIRE-3 (n = 288, validation cohort). Patients receiving FOLFIRI plus cetuximab in FIRE-3 (n = 264) served as a control cohort. The interaction between genotype and primary tumor location with clinical outcomes was examined. Genomic DNA isolated from whole blood or tumor tissue was analyzed by PCR-based direct sequencing. RESULTS: Patients with an IL6 rs2069837 G allele treated with FOLFIRI plus bevacizumab had an inferior PFS than those with the A/A genotype in TRIBE [9.4 vs. 11.1 months; HR = 1.53; 95% confidence interval (CI), 1.12-2.10; P = 0.004] and FIRE-3 (8.8 vs. 10.9 months; HR = 1.40; 95% CI, 1.06-1.85; P = 0.015). These associations were confirmed in multivariable analyses and were not seen in the control cohort. In subgroup analysis, the effect of IL6 rs2069837 on PFS was present only in patients with left-sided cancers, but the test for interaction was not significant. CONCLUSIONS: IL6 rs2069837 genotype is a clinically relevant prognostic factor in mCRC patients treated with first-line bevacizumab-based chemotherapy. Clin Cancer Res; 22(13); 3218-26. (c)2016 AACR. PMID- 26839148 TI - Hemoglobin-carbon nanotube derived noble-metal-free Fe5C2-based catalyst for highly efficient oxygen reduction reaction. AB - High performance non-precious cathodic catalysts for oxygen reduction reaction (ORR) are vital for the development of energy materials and devices. Here, we report an noble metal free, Fe5C2 nanoparticles-studded sp(2) carbon supported mesoporous material (CNTHb-700) as cathodic catalyst for ORR, which was prepared by pyrolizing the hybrid adduct of single walled carbon nanotubes (CNT) and lyophilized hemoglobin (Hb) at 700 degrees C. The catalyst shows onset potentials of 0.92 V in 0.1 M HClO4 and in 0.1 M KOH which are as good as commercial Pt/C catalyst, giving very high current density of 6.34 and 6.69 mA cm(-2) at 0.55 V vs. reversible hydrogen electrode (RHE), respectively. This catalyst has been confirmed to follow 4-electron mechanism for ORR and shows high electrochemical stability in both acidic and basic media. Catalyst CNTHb-700 possesses much higher tolerance towards methanol than the commercial Pt/C catalyst. Highly efficient catalytic properties of CNTHb-700 could lead to fundamental understanding of utilization of biomolecules in ORR and materialization of proton exchange membrane fuel cells for clean energy production. PMID- 26839147 TI - Immunogenicity and protective efficacy of recombinant Clostridium difficile flagellar protein FliC. AB - Clostridium difficile is a Gram-positive bacillus and is the leading cause of toxin-mediated nosocomial diarrhea following antibiotic use. C. difficile flagella play a role in colonization, adherence, biofilm formation, and toxin production, which might contribute to the overall virulence of certain strains. Human and animal studies indicate that anti-flagella immune responses may play a role in protection against colonization by C. difficile and subsequent disease outcome. Here we report that recombinant C. difficile flagellin (FliC) is immunogenic and protective in a murine model of C. difficile infection (CDI) against a clinical C. difficile strain, UK1. Passive protection experiments using anti-FliC polyclonal serum in mice suggest this protection to be antibody mediated. FliC immunization also was able to afford partial protection against CDI and death in hamsters following challenge with C. difficile 630Deltaerm. Additionally, immunization against FliC does not have an adverse effect on the normal gut flora of vaccinated hamsters as evidenced by comparing the fecal microbiome of vaccinated and control hamsters. Therefore, the use of FliC as a vaccine candidate against CDI warrants further testing. PMID- 26839149 TI - Standardized extract of Tinospora crispa stimulates innate and adaptive immune responses in Balb/c mice. AB - Standardized extract of Tinospora crispa has been shown to exhibit immunostimulatory effects on innate immune responses in Wistar-Kyoto rats by enhancing neutrophil and T cell-mediated immunity. In this study the immunostimulatory effects of T. crispa were further investigated on the cellular immune response by determining its effect on nitric oxide (NO) production ability, peritoneal macrophage phagocytosis and delayed type hypersensitivity (DTH), whereas the humoral immune response was evaluated through the measurement of serum immunoglobulins (IgG and IgM) and serum lysozyme levels. Male Balb/c mice were immunized with 200 MUL of 5 * 10(9) sheep red blood cells (sRBCs) per mL on day 0 and orally administered with 50, 100 and 200 mg per kg of ethanol extract of T. crispa for 14 days. Syringin and magnoflorine were qualitatively and quantitatively analyzed in the extract as chemical markers by using a validated reversed-phase high performance liquid chromatography method. T. crispa extract (TCE) considerably improved the peritoneal macrophages' ability to engulf FITC-labeled E. coli in a dose-dependent manner. TCE also dose-dependently promoted NO production in peritoneal macrophages activated by a lipopolysaccharide (LPS) and markedly potentiated the sRBS-induced swelling rate of the mice paw in DTH. The extract significantly enhanced the level of serum immunoglobulins, showing maximum activity at 100 mg kg(-1). Compared to the control groups, the serum lysozyme level and myeloperoxidase (MPO) activity were significantly higher in extract-treated groups. These findings suggest that T. crispa possesses strong immunostimulatory activities and might act as a natural immunomodulator as well as a potential nutraceutical for the modulation of the immune response. PMID- 26839150 TI - [Of hair, customs and sacred rituals]. PMID- 26839146 TI - Updates on the risk factors for latent tuberculosis reactivation and their managements. AB - The preventive treatment of latent tuberculosis infection (LTBI) is of great importance for the elimination and control of tuberculosis (TB) worldwide, but existing screening methods for LTBI are still limited in predicting the onset of TB. Previous studies have found that some high-risk factors (including human immunodeficiency virus (HIV), organ transplantation, silicosis, tumor necrosis factor-alpha blockers, close contacts and kidney dialysis) contribute to a significantly increased TB reactivation rate. This article reviews each risk factor's association with TB and approaches to address those factors. Five regimens are currently recommended by the World Health Organization, and no regimen has shown superiority over others. In recent years, studies have gradually narrowed down to the preventive treatment of LTBI for high-risk target groups, such as silicosis patients, organ-transplantation recipients and HIV infected patients. This review discusses regimens for each target group and compares the efficacy of different regimens. For HIV patients and transplant recipients, isoniazid monotherapy is effective in treating LTBI, but for others, little evidence is available at present. PMID- 26839151 TI - Proteomic characterization of macro-, micro- and nano-extracellular vesicles derived from the same first trimester placenta: relevance for feto-maternal communication. AB - STUDY QUESTION: What proteins are carried by extracellular vesicles (EVs) released from normal first trimester placentae? SUMMARY ANSWER: One thousand five hundred and eighty-five, 1656 and 1476 proteins were characterized in macro-, micro- and nano-vesicles, respectively, from first trimester placentae, with all EV fractions being enriched for proteins involved in vesicle transport and inflammation. WHAT IS KNOWN ALREADY: Placental EVs are being increasingly recognized as important mediators of both healthy and pathological pregnancies. However, current research has focused on detecting changes in specific proteins in particular fractions of vesicles during disease. This is the first study to investigate the full proteome of different-sized fractions of EVs from the same first trimester placenta and highlights the differences/similarities between the vesicle fractions. STUDY DESIGN, SIZE, DURATION: A well-established ex vivo placental explant culture model was used to generate macro-, micro- and nano vesicles from 56 first trimester placentae. Vesicle fractions were collected by differential ultracentrifugation, quantified and characterized. PARTICIPANTS/MATERIALS, SETTING, METHODS: Placental macro-, micro- and nano vesicles were characterized by microscopy, dynamic light scattering and nanoparticle tracking analysis. The proteome of each EV fraction was interrogated using liquid chromatography-coupled tandem mass spectrometry. Results were validated by semi-quantitative western blotting. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 1585, 1656 and 1476 proteins were identified in macro-, micro- and nano-vesicles, respectively. One thousand one hundred and twenty-five proteins were shared between all three fractions while up to 223 proteins were unique to each fraction. Gene Ontology pathway analysis showed an enrichment of proteins involved in vesicle transport and inflammation in all three fractions of EVs. The expression levels of proteins involved in internalization of vesicles (annexin V, calreticulin, CD31, CD47), the complement pathway [C3, decay accelerating factor (DAF), membrane cofactor protein (MCP), protectin] and minor histocompatibility antigens [ATP-dependent RNA helicase (DDX3), ribosomal protein S4 (RPS4)] were different between different-sized EVs. LIMITATIONS, REASONS FOR CAUTION: This study is largely hypothesis-generating in nature. It is important to validate these findings using EVs isolated from maternal plasma and the function of the different EV fractions would need further investigation. WIDER IMPLICATIONS OF THE FINDINGS: Our results support the concept that various EV factions can interact with different maternal cells and have unique effects to mediate feto-maternal communication during early pregnancy. This study also provides a list of candidate proteins, which may inform the identification of robust markers that can be used to isolate placental vesicles from the maternal blood in the future. STUDY FUNDING/COMPETING INTERESTS: M.T. is a recipient of the University of Auckland Health Research Doctoral Scholarship and the Freemasons Postgraduate Scholarship. This project was supported by a School of Medicine Performance-based research fund (PBRF) grant awarded to L.W.C. No authors have any conflicts of interest to disclose. PMID- 26839153 TI - Rationally designed siRNAs without miRNA-like off-target repression. AB - Small interfering RNAs (siRNAs) have been developed to intentionally repress a specific gene expression by directing RNA-induced silencing complex (RISC), mimicking the endogenous gene silencer, microRNAs (miRNAs). Although siRNA is designed to be perfectly complementary to an intended target mRNA, it also suppresses hundreds of off-targets by the way that miRNAs recognize targets. Until now, there is no efficient way to avoid such off-target repression, although the mode of miRNA-like interaction has been proposed. Rationally based on the model called "transitional nucleation" which pre-requires base-pairs from position 2 to the pivot (position 6) with targets, we developed a simple chemical modification which completely eliminates miRNA-like off-target repression (0%), achieved by substituting a nucleotide in pivot with abasic spacers (dSpacer or C3 spacer), which potentially destabilize the transitional nucleation. Furthermore, by alleviating steric hindrance in the complex with Argonaute (Ago), abasic pivot substitution also preserves near-perfect on-target activity (~80-100%). Abasic pivot substitution offers a general means of harnessing target specificity of siRNAs to experimental and clinical applications where misleading and deleterious phenotypes from off-target repression must be considered. [BMB Reports 2016; 49(3): 135-136]. PMID- 26839152 TI - Use of Optical Fiber Imported Intra-Tissue Photodynamic Therapy for Treatment of Moderate to Severe Acne Vulgaris. AB - BACKGROUND: To treat moderate to severe acne vulgaris, we developed an optical fiber imported intra-tissue photodynamic therapy: the optical fiber irradiation 5 aminolevulinic acid photodynamic therapy (OFI-ALA-PDT). The aim of this study was to compare the treatment effect and tolerability of OFI-ALA-PDT versus traditional ALA-PDT in the treatment of moderate to severe acne vulgaris. MATERIAL/METHODS: 60 patients with facial acne enrolled into this study were randomly divided into an OFI-ALA-PDT group and a traditional ALA-PDT group, with 30 patients in each group. The difference between these 2 groups was the red light irradiation methods used. In the OFI-ALA-PDT group we used intra-tissue irradiation (import the red light directly into the target lesion with optical fiber) for 5 min, while the traditional ALA-PDT group received whole-face irradiation for 20 min. All patients received 1 irradiation every 7 to 10 days for a total of 6 irradiations. Treatment effects and adverse reactions were recorded after the 4th and 6th irradiation, and at 4, 8, 16 weeks after the entire treatment. RESULTS: After the 4th irradiation, significantly different effective rates were observed in these groups (90.0% for the OFI-ALA-PDT group and 66.7% for the control group). However, no significant difference in effective rate was recorded in the later observations. There were 182 adverse reactions in the OFI-ALA-PDT group and 497 in the control group, which showed a significant difference (P<0.05). CONCLUSIONS: OFI-ALA-PDT showed improved treatment effective rate in the early stage of irradiation, and it had fewer adverse reactions. PMID- 26839154 TI - c-Jun N-terminal Kinase (JNK) induces phosphorylation of amyloid precursor protein (APP) at Thr668, in okadaic acid-induced neurodegeneration. AB - Several lines of evidence have revealed that phosphorylation of amyloid precursor protein (APP) at Thr668 is involved in the pathogenesis of Alzheimer's disease (AD). Okadaic acid (OA), a protein phosphatase-2A inhibitor, has been used in AD research models to increase tau phosphorylation and induce neuronal death. We previously showed that OA increased levels of APP and induced accumulation of APP in axonal swellings. In this study, we found that in OA-treated neurons, phosphorylation of APP at Thr668 increased and accumulated in axonal swellings by c-jun N-terminal kinase (JNK), and not by Cdk5 or ERK/MAPK. These results suggest that JNK may be one of therapeutic targets for the treatment of AD. [BMB Reports 2016; 49(7): 376-381]. PMID- 26839155 TI - Humans and seasonal climate variability threaten large-bodied coral reef fish with small ranges. AB - Coral reefs are among the most species-rich and threatened ecosystems on Earth, yet the extent to which human stressors determine species occurrences, compared with biogeography or environmental conditions, remains largely unknown. With ever increasing human-mediated disturbances on these ecosystems, an important question is not only how many species can inhabit local communities, but also which biological traits determine species that can persist (or not) above particular disturbance thresholds. Here we show that human pressure and seasonal climate variability are disproportionately and negatively associated with the occurrence of large-bodied and geographically small-ranging fishes within local coral reef communities. These species are 67% less likely to occur where human impact and temperature seasonality exceed critical thresholds, such as in the marine biodiversity hotspot: the Coral Triangle. Our results identify the most sensitive species and critical thresholds of human and climatic stressors, providing opportunity for targeted conservation intervention to prevent local extinctions. PMID- 26839156 TI - Atherogenic Lipoproteins in Subclinical Hypothyroidism and Their Relationship with Hepatic Lipase Activity: Response to Replacement Treatment with Levothyroxine. AB - BACKGROUND: Qualitative lipoprotein changes, such as an increase in fasting remnants, are reported in subclinical hypothyroidism (SCH). It was hypothesized that such changes are due to reduced hepatic lipase (HL) activity in SCH: HL is an enzyme regulated by thyroid hormones, and is involved in the degradation of triglyceride (TG)-rich remnants. This study aimed to quantify remnant-like lipoproteins (RLP), small dense LDL (sdLDL), and HL activity in women with SCH, and to assess these parameters after levothyroxine replacement therapy. METHODS: This was an observational cross-sectional study with a subsequent longitudinal follow-up. Findings in women with thyrotropin levels >4.5 mIU/L (SH group) were compared with age- and body mass index (BMI)-matched euthyroid women (control group). In addition, a subgroup analysis was undertaken in SCH women who chose to receive levothyroxine treatment (0.9 MUg/kg/day) for 6 months. RLP was quantified by measuring cholesterol (RLP-C) and triglycerides (RLP-TG) after immunoaffinity chromatography, and sdLDL by automated standardized methods; HL activity was measured in post-heparin plasma. RESULTS: The SCH group included 37 women; 29 women were included in the control group. In addition, 22 women with SCH were included in the subgroup analysis (levothyroxine treatment). Significantly higher RLP values were observed in the SCH group than in the control group: RLP-C (median [range], mg/dL): 20.3 (5.8-66.8) versus 10.2 (2.7-36.3), p = 0.005; RLP TG (mg/dL): 26.3 (3.2-123.3) versus 12.1 (2.5-61.6), p = 0.033. HL activity (mean +/- standard deviation [SD], MUmol free fatty acid/mL post-heparin plasma.h)-9.83 +/- 4.25 versus 9.92 +/- 5.20, p = 0.707-and sdLDL levels (mg/dL)-23.1 +/- 10.7 versus 22.6 +/- 8.4, p = 0.83-were similar. After levothyroxine, RLP-C decreased 21.5 (5.8-66.8) versus 17.2 (4.1-45.6), p = 0.023-and HL increased-9.75 +/- 4.04 versus 11.86 +/- 4.58, p = 0.012-in the subgroup of SCH women. No changes in sdLDL were observed. CONCLUSIONS: Women with SCH have higher RLP levels than matched controls do, but their RLP-C levels decrease significantly following levothyroxine therapy. Furthermore, HL activity also increases after levothyroxine therapy and can be interpreted as a possible explanation for the decrease in RLP-C. PMID- 26839157 TI - Spindle cell oncocytoma of adenohypophysis: Report of a case and immunohistochemical review of literature. AB - We present a case of spindle cell oncocytoma (SCO) of the adenohypophysis in a 70 year-old Vietnamese male. The patient was admitted to Cho Ray Hospital after suffering from headache and visual disturbance for 6 months. Clinicians detected a 60*55*45 mm(3) mass located in the suprasellar-sellar region. Histopathologically, the resected tumor was composed of spindle cells with oncocytic appearance. Immunohistochemical examination revealed expression of anti mitochondria antibody (AMA), vimentin, thyroid transcription factor 1 (TTF-1), epithelial membrane antigen (EMA) and galectin-3. These histologic and immunohistochemical findings are suggestive of SCO. PMID- 26839158 TI - Interobserver reproducibility for HER2/neu immunohistochemistry: A comparison of reproducibility for the HercepTestTM and the 4B5 antibody clone. AB - BACKGROUND: IHC results for HER2/neu vary with replicate testing using the same antibody clone and when alternate clones are utilized. A number of factors appear to be responsible for this variability, including fixation times, equipment utilized and training and experience of staff. A number of studies have documented interobserver variability for a single antibody clone but few have evaluated reproducibility between antibody clones and which clones demonstrate the highest degree of interobserver reproducibility. DESIGN: We studied a series of 93 cases stained by both the HercepTestTM and the 4B5 clone for interobserver reproducibility. Formalin-fixed, paraffin-embedded sections were stained by the immunohistochemical technique using the manufactures directions for both the HercepTestTM and the 4B5 clone. FISH testing was performed on formalin-fixed paraffin embedded sections according to the PathVysion HER-2 DNA probe kit instructions. RESULTS: Absolute agreement rate for Hercep was 85%. Absolute agreement for 4B5 was 69%. This difference was statistically significant (p<0.0001). The chance-corrected agreement (weighted kappa) for the HercepTestTM was 79% and 71% for 4B5 (p<0.0001). Absolute agreement between antibody clones was 58% with the chance corrected agreement being 51%. Absolute agreement of 4B5 with FISH was significantly greater than that of the HercepTestTM (54% vs 35%). CONCLUSION: Agreement between evaluators was greater with the HercepTest. However, agreement with FISH results was superior for the 4B5 clone. Interobserver agreement was less than the 95% agreement threshold recommended by the ASCO/CAP guidelines for development of a new testing method for HER2 evaluation. PMID- 26839159 TI - Extracutaneous intravascular histiocytosis of the aortic valve: Report of two cases. AB - Intravascular histiocytosis (IVH) is a rare condition of uncertain pathogenesis often associated with rheumatoid arthritis (RA) exclusively observed in the skin. In a retrospective study of 207 consecutive cases of aortic valve disease, we observed two cases of IVH characterized by the presence of thin-walled, dilated blood vessels containing collections of CD68+ and CD163+ mononuclear histiocytes. Immunostains for CD31, CD34, and D2-40 confirmed the intravascular location of these histiocytes. One of the two cases was associated with RA. This case was observed among 41 cases of RA with calcific aortic valve stenosis. The other case was detected among 152 cases of calcific aortic valve stenosis in isolation. A total of 14 valves showed no calcification. IVH can manifest in the aortic valve and be associated with systemic disease. In contrast to other cases, the vessels observed in this study exhibited negative expression of the lymphatic marker D2 40. Our findings expand on the previously described location features of IVH. PMID- 26839160 TI - Human intestinal spirochetosis and its relationship to sessile serrated adenomas in an Australian population. PMID- 26839161 TI - Can Nup88 expression be associated with atypical endometrial hyperplasia and endometrial cancer? A preliminary study. AB - BACKGROUND: Nup88 is overexpressed in a number of types of carcinomas and is associated with myometrial invasion, but its exact expression pattern in endometrial cancer and premalignant lesions is unknown. AIMS: To evaluate the role of Nup88 in endometrial cancers and atypical endometrial hyperplasia and its clinicopathological significance. METHODS: Nup88 expression was examined by immunohistochemistry in samples from 104 endometrial cancers, 21 atypical endometrial hyperplasia lesions, and 40 normal endometria. All samples were from patients who underwent surgery at the First Hospital of Hebei Medical University (Shijiazhuang, China) between April 2006 and December 2009. Nup88 expression was compared between the groups and associations were assessed between Nup88 and clinicopathological characteristics of the subjects. RESULTS: Nup88 expression in cancer (76% of samples) and atypical hyperplasia (91%) was significantly higher compared to normal endometrium (33%, both P<0.001), but there was no significant difference between endometrial cancer and atypical hyperplasia (P=0.237). The expression of Nup88 increased significantly with increasing exposure time to estrogen (P=0.033). CONCLUSIONS: Nup88 may be related to the occurrence of endometrial cancers and premalignant lesions. Nup88 might be a useful biomarker for pre-malignant lesions and early-stage endometrial cancer. PMID- 26839162 TI - In Pursuit of Theoretical Ground in Behavior Change Support Systems: Analysis of Peer-to-Peer Communication in a Health-Related Online Community. AB - BACKGROUND: Research studies involving health-related online communities have focused on examining network structure to understand mechanisms underlying behavior change. Content analysis of the messages exchanged in these communities has been limited to the "social support" perspective. However, existing behavior change theories suggest that message content plays a prominent role reflecting several sociocognitive factors that affect an individual's efforts to make a lifestyle change. An understanding of these factors is imperative to identify and harness the mechanisms of behavior change in the Health 2.0 era. OBJECTIVE: The objective of this work is two-fold: (1) to harness digital communication data to capture essential meaning of communication and factors affecting a desired behavior change, and (2) to understand the applicability of existing behavior change theories to characterize peer-to-peer communication in online platforms. METHODS: In this paper, we describe grounded theory-based qualitative analysis of digital communication in QuitNet, an online community promoting smoking cessation. A database of 16,492 de-identified public messages from 1456 users from March 1-April 30, 2007, was used in our study. We analyzed 795 messages using grounded theory techniques to ensure thematic saturation. This analysis enabled identification of key concepts contained in the messages exchanged by QuitNet members, allowing us to understand the sociobehavioral intricacies underlying an individual's efforts to cease smoking in a group setting. We further ascertained the relevance of the identified themes to theoretical constructs in existing behavior change theories (eg, Health Belief Model) and theoretically linked techniques of behavior change taxonomy. RESULTS: We identified 43 different concepts, which were then grouped under 12 themes based on analysis of 795 messages. Examples of concepts include "sleepiness," "pledge," "patch," "spouse," and "slip." Examples of themes include "traditions," "social support," "obstacles," "relapse," and "cravings." Results indicate that themes consisting of member-generated strategies such as "virtual bonfires" and "pledges" were related to the highest number of theoretical constructs from the existing behavior change theories. In addition, results indicate that the member generated communication content supports sociocognitive constructs from more than one behavior change model, unlike the majority of the existing theory-driven interventions. CONCLUSIONS: With the onset of mobile phones and ubiquitous Internet connectivity, online social network data reflect the intricacies of human health behavior as experienced by health consumers in real time. This study offers methodological insights for qualitative investigations that examine the various kinds of behavioral constructs prevalent in the messages exchanged among users of online communities. Theoretically, this study establishes the manifestation of existing behavior change theories in QuitNet-like online health communities. Pragmatically, it sets the stage for real-time, data-driven sociobehavioral interventions promoting healthy lifestyle modifications by allowing us to understand the emergent user needs to sustain a desired behavior change. PMID- 26839163 TI - Quantum dots-based double imaging combined with organic dye imaging to establish an automatic computerized method for cancer Ki67 measurement. AB - As a widely used proliferative marker, Ki67 has important impacts on cancer prognosis, especially for breast cancer (BC). However, variations in analytical practice make it difficult for pathologists to manually measure Ki67 index. This study is to establish quantum dots (QDs)-based double imaging of nuclear Ki67 as red signal by QDs-655, cytoplasmic cytokeratin (CK) as yellow signal by QDs-585, and organic dye imaging of cell nucleus as blue signal by 4',6-diamidino-2 phenylindole (DAPI), and to develop a computer-aided automatic method for Ki67 index measurement. The newly developed automatic computerized Ki67 measurement could efficiently recognize and count Ki67-positive cancer cell nuclei with red signals and cancer cell nuclei with blue signals within cancer cell cytoplasmic with yellow signals. Comparisons of computerized Ki67 index, visual Ki67 index, and marked Ki67 index for 30 patients of 90 images with Ki67 <= 10% (low grade), 10% < Ki67 < 50% (moderate grade), and Ki67 >= 50% (high grade) showed computerized Ki67 counting is better than visual Ki67 counting, especially for Ki67 low and moderate grades. Based on QDs-based double imaging and organic dye imaging on BC tissues, this study successfully developed an automatic computerized Ki67 counting method to measure Ki67 index. PMID- 26839164 TI - Cardiac Magnetic Resonance Imaging Predictors of Short-Term Outcomes after High Risk Coronary Surgery. AB - BACKGROUND: The euroSCORE II is a widely used pre-coronary artery bypass graft surgery (CAGS) risk score, but its predictive power lacks the specificity to predict outcomes in high-risk patients (16) and left ventricular (LV) dysfunction (<40%) based on 2D-echocardiography who underwent CAGS and in whom CMRI (1.5T) was performed preoperatively were retrospectively studied. Cardiac magnetic resonance imaging parameters were assessed in patients who either had complications immediately post-surgery (n=35), six weeks post-surgery (n=20) or were uncomplicated. RESULTS: The average age of patients recruited was 69+/-5 years with high euroSCORE II (22+/-4) and low 2D-echocardiography LV ejection fraction (38%+/-2%). Cardiac magnetic resonance imaging results demonstrated that those with immediate complications had higher LV scar/infarct burden as a proportion of LV mass (17+/-3% vs 10+/-3%; p=0.04) with lower circumferential relaxation index (2.5+/-0.46 vs 2.8+/-0.56; p=0.05) compared to those with no complications. Early mortality from surgery was 17% (n=9) and was associated with lower RV stroke volume (55+/-12 vs 68+/-18; p=0.03) and higher LV infarct scar/burden (18+/-2% vs 10+/-2%, p=0.04). Cardiac magnetic resonance imaging showed patients with complications at six weeks post-surgery had higher LV scar/infarct burden (14.5+/-2% vs 6.8+/-2%, p=0.03) compared to those without complications. CONCLUSION: Cardiac magnetic resonance imaging preoperative LV and RV parameters are valuable in assessing the likelihood of successful outcomes from CAGS in high-risk patients with LV dysfunction. PMID- 26839165 TI - When Atrial Fibrillation Co-Exists with Coronary Artery Disease in Patients with Prior Coronary Intervention - Does Ablation Benefit? AB - BACKGROUND: Atrial fibrillation (AF) can be associated with an increased risk of developing coronary artery disease (CAD) due to mechanisms of inflammation, endothelial dysfunction and adverse atrial remodelling. It is unclear if adverse coronary events can be further reduced after successful catheter ablation of AF. We hypothesise that AF ablation and sinus maintenance could reduce future adverse cardiac events in patients with underlying CAD. METHODS: A total of 310 patients with drug-refractory paroxysmal AF and prior history of percutaneous coronary intervention (PCI) for underlying CAD were recruited in the retrospective case control study. Of these, 155 patients underwent AF ablation (the Ablation Group), while 155 patients received medical treatment (the Medical Group). All patients were followed up for major adverse cardiac events, including acute coronary syndrome requiring hospitalisation, stroke, pulmonary embolism and mortality. RESULTS: The clinical characteristics were comparable between the two groups, except for higher antiarrhythmic drug use in the Medical Group. During a follow up duration of 61+/-32 months, all-cause mortality (8.4% vs. 1.3%, p=0.004) and the overall major adverse events (47.7% vs. 12.3%, p<0.001) were significantly higher in the Medical Group than the Ablation Group. There were also more instances of stroke (10.3% vs. 3.2%, p=0.013) and acute coronary syndrome requiring hospitalisation (29% vs. 7.1%, p<0.001) in the Medical Group than the Ablation Group. Multivariate analysis confirmed that non-ablation was an independent risk factor for major adverse events (p<0.001, HR 3.4, 95% confidence interval 1.9-5.9). CONCLUSION: In PAF patients with established CAD who underwent PCI, catheter ablation could lead to fewer major adverse cardiac events compared to medical therapy. PMID- 26839166 TI - Fibrinogen and the Severity of Coronary Atherosclerosis among Adults with and without Statin Treatment: Lipid as a mediator. AB - BACKGROUND: It has been proposed that plasma fibrinogen is associated with lipid levels and increased cardiovascular risk. However, the interrelationship has not been well-elucidated. We hypothesise that lipids may be potential mediators. METHODS: We enrolled 4748 consecutive subjects scheduled for coronary angiography in this study. The severity of coronary atherosclerosis was assessed by Gensini score (GS). By principle component analysis, a multi-marker lipid index was extracted weighting the coefficients of six atherogenic lipid parameters: total cholesterol (TC), low-density lipoprotein-cholesterol, non-high-density lipoprotein-cholesterol (non-HDL-C), apolipoprotein (apo) B, apoB/apoA1, and TC/HDL-C ratio. Moreover, using mediation analysis, the relationship between fibrinogen and lipids with high GS was evaluated. RESULTS: Fibrinogen was positively associated with GS after adjustment (beta=0.100, p<0.001). We stratified our analyses by statin use status and found that subjects in the upper fibrinogen tertiles had higher levels of atherogenic lipid parameters irrespective of statin status (p<0.001, all). Significantly, we observed a synergistic effect of fibrinogen and concurrent elevated lipid index for high GS. The adjusted odds ratios were greater in participants who had high fibrinogen levels and also high lipid index compared to those with low lipid index [on statin: 1.725(1.258-2.364) vs. 1.261(0.962-1.652); not on statin: 2.197(1.450 3.328) vs. 1.166(0.417-3.258)]. Specifically, mediation analysis indicated that around 24% of the effect of fibrinogen on high GS was mediated by lipid index, which was attenuated to 13% by statin status. CONCLUSIONS: The increased risk of fibrinogen on coronary atherosclerosis appeared to be enhanced by the high atherogenic lipid levels, which mediated around 24% of this effect. PMID- 26839167 TI - [Paediatric rheumatology: The importance of anamnesis and physical examination]. PMID- 26839168 TI - [Post-natally acquired torticollis: Giant cavernous cerebellum]. PMID- 26839169 TI - The Times They Are a Changin': Neuropsychology and Integrated Care Teams. AB - OBJECTIVE: To gather illustrative data from clinical neuropsychologists who are working in integrated care settings in order to provide an initial blueprint for moving forward in this new era of health care. METHOD: A survey was designed to illustrate the ways in which neuropsychologists are participating in integrated care teams and distributed on major neuropsychology listservs. The survey evaluated the settings, roles, services provided, practice issues, remuneration, and impact of neuropsychologists' participation in integrated care teams with respect to patient care and health outcomes. Frequencies were used to summarize the findings as well as qualitative coding of narrative responses. RESULTS: There were 412 respondents to the survey and 261 of those indicated that they worked in at least one integrated care setting. Neuropsychologists work in a variety of integrated care settings and provide diverse services which contribute to improved patient care and outcomes. CONCLUSIONS: Three primary themes emerge from the findings with regard to the engagement and teams: advocacy, collaboration, and communication. We argue for the need for more easily accessible outcome studies illustrating the clinical benefits and cost-savings associated with inclusion of neuropsychologists in integrated care teams. In addition, educational and training initiatives are needed to better equip current and future clinical neuropsychologists to function effectively in integrated care settings. PMID- 26839170 TI - Self-assembly of arene ruthenium acylpyrazolone fragments to tetranuclear metallacycles. Molecular structures and solid-state (15)N CPMAS NMR correlations. AB - Reactions of [(eta(6)-cymene)Ru(MU-Cl)Cl]2 with acylpyrazolone ligands HQ' (HQ' in general; in detail, HQ(CH2Cl) = 2-chloro-1-(5-hydroxy-3-methyl-1-phenyl-1H pyrazol-4-yl)ethanone), HQ(hex) = 1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4 yl)heptan-1-one), HQ(nPe) = 1-(5-hydroxy-3-methyl-1-phenyl-1H-pyrazol-4-yl)-3,3 dimethylbutan-1-one)), in the presence of base, gave the corresponding [(eta(6) cymene)Ru(Q')Cl] mononuclear complexes. They react with AgX (where X = O3SCF3 or BF4) in dry acetone affording cationic metalla-cycles [(eta(6) cymene)Ru(Q')]4(X)4. The complexes were fully characterized by analytical and spectroscopic methods and the solid-state structures of mononuclear and tetranuclear complexes have been determined by single-crystal X-ray diffraction. The hapticity of the acylpyrazolone ligands to the Ru metal centre has also been established by (13)C and (15)N CPMAS NMR spectroscopy for the complexes where the lack of crystallinity prevented the elucidation of the crystal structure by SCXRD data. PMID- 26839172 TI - Role of radiation therapy in non-melanoma cancers, lymphomas and sarcomas of the skin: Systematic review and best practice in 2016. AB - Radiotherapy (RT) has been used for the treatment of skin cancers since very early after the discovery of X-rays. Indications for radiotherapy in non-melanoma cancers are controversial, and are usually decided according to the tumor type and the possibility of curing the patient with surgery. The introduction of sophisticated surgery techniques and the information of the general population on potential late radiation-induced toxicity and carcinogenesis have led to limiting radiation indications in the dermatologist community. However, radiotherapy has undergone considerable development, including technological advances, to enable limiting doses to the organs at risk. Thus, side effects due to high doses and/or the use of old radiotherapy (RT) techniques have been significantly decreased. In this systematic review we aim to discuss indications of radiotherapy in non melanoma skin cancers and focus on new advances that may lead to rehabilitating this treatment option according to the tumor's radiosensitivity and the clinical benefit/risk ratio. Finally, for each type of cancer, we suggest "the best RT practice". PMID- 26839171 TI - Genome-scale study reveals reduced metabolic adaptability in patients with non alcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) is a major risk factor leading to chronic liver disease and type 2 diabetes. Here we chart liver metabolic activity and functionality in NAFLD by integrating global transcriptomic data, from human liver biopsies, and metabolic flux data, measured across the human splanchnic vascular bed, within a genome-scale model of human metabolism. We show that an increased amount of liver fat induces mitochondrial metabolism, lipolysis, glyceroneogenesis and a switch from lactate to glycerol as substrate for gluconeogenesis, indicating an intricate balance of exacerbated opposite metabolic processes in glycemic regulation. These changes were associated with reduced metabolic adaptability on a network level in the sense that liver fat accumulation puts increasing demands on the liver to adaptively regulate metabolic responses to maintain basic liver functions. We propose that failure to meet excessive metabolic challenges coupled with reduced metabolic adaptability may lead to a vicious pathogenic cycle leading to the co-morbidities of NAFLD. PMID- 26839173 TI - Updates on the genetics and the clinical impacts on phaeochromocytoma and paraganglioma in the new era. AB - Genetic mutations of phaeochromocytoma (PCC) and paraganglioma (PGL) are mainly classified into two major clusters. Cluster 1 mutations are involved with the pseudo hypoxic pathway and comprised of PHD2, VHL, SDHx, IDH, HIF2A, MDH2 and FH mutated PCC/PGL. Cluster 2 mutations are associated with abnormal activation of kinase signalling pathways and included mutations of RET, NF1, KIF1Bbeta, MAX and TMEM127. In addition, VHL, SDHx (cluster 1 genes) and RET, NF1 (cluster 2 genes) germline mutations are involved in the neuronal precursor cell pathway in the pathogeneses of PCC/PGL. Also, GDNF, H-ras, K-ras, GNAS, CDKN2A (p16), p53, BAP1, BRCA1&2, ATRX and KMT2D mutations have roles in the development of PCC/PGLs. Overall, known genetic mutations account for the pathogenesis of approximately 60% of PCC/PGLs. Genetic mutations, pathological parameters and biochemical markers are used for better prediction of the outcome of patients with this group of tumours. Immunohistochemistry and gene sequencing can ensure a more effective detection, prediction of malignant potential and treatment of PCC/PCLs. PMID- 26839175 TI - Thermodynamic approach to boron nitride nanotube solubility and dispersion. AB - Inadequate dispersion of nanomaterials is a critical issue that significantly limits the potential properties of nanocomposites and when overcome, will enable further enhancement of material properties. The most common methods used to improve dispersion include surface functionalization, surfactants, polymer wrapping, and sonication. Although these approaches have proven effective, they often achieve dispersion by altering the surface or structure of the nanomaterial and ultimately, their intrinsic properties. Co-solvents are commonly utilized in the polymer, paint, and art conservation industries to selectively dissolve materials. These co-solvents are utilized based on thermodynamic interaction parameters and are chosen so that the original materials are not affected. The same concept was applied to enhance the dispersion of boron nitride nanotubes (BNNTs) to facilitate the fabrication of BNNT nanocomposites. Of the solvents tested, dimethylacetamide (DMAc) exhibited the most stable, uniform dispersion of BNNTs, followed by N,N-dimethylformamide (DMF), acetone, and N-methyl-2 pyrrolidone (NMP). Utilizing the known Hansen solubility parameters of these solvents in comparison to the BNNT dispersion state, a region of good solubility was proposed. This solubility region was used to identify co-solvent systems that led to improved BNNT dispersion in poor solvents such as toluene, hexane, and ethanol. Incorporating the data from the co-solvent studies further refined the proposed solubility region. From this region, the Hansen solubility parameters for BNNTs are thought to lie at the midpoint of the solubility sphere: 16.8, 10.7, and 9.0 MPa(1/2) for deltad, deltap, and deltah, respectively, with a calculated Hildebrand parameter of 21.8 MPa(1/2). PMID- 26839174 TI - A role for Mfb1p in region-specific anchorage of high-functioning mitochondria and lifespan in Saccharomyces cerevisiae. AB - Previous studies indicate that replicative lifespan in daughter cells of Sacchraromyces cerevisiae depends on the preferential inheritance of young, high functioning mitochondria. We report here that mitochondria are functionally segregated even within single mother cells in S. cerevisiae. A high-functioning population of mitochondria accumulates at the tip of the mother cell distal to the bud. We find that the mitochondrial F-box protein (Mfb1p) localizes to mitochondria in the mother tip and is required for mitochondrial anchorage at that site, independent of the previously identified anchorage protein Num1p. Deletion of MFB1 results in loss of the mother-tip-localized mitochondrial population, defects in mitochondrial function and premature replicative ageing. Inhibiting mitochondrial inheritance to buds, by deletion of MMR1, in mfb1Delta cells restores mitochondrial distribution, promotes mitochondrial function and extends replicative lifespan. Our results identify a mechanism that retains a reservoir of high-functioning mitochondria in mother cells and thereby preserves maternal reproductive capacity. PMID- 26839176 TI - Erratum: The structure of Legionella pneumophila LegK4 type four secretion system (T4SS) effector reveals a novel dimeric eukaryotic-like kinase. PMID- 26839177 TI - Questions your patients may have about Zika virus. PMID- 26839178 TI - Frontally eluted components procedure with thin layer chromatography as a mode of sample preparation for high performance liquid chromatography quantitation of acetaminophen in biological matrix. AB - A new concept of using thin-layer chromatography to sample preparation for the quantitative determination of solute/s followed by instrumental techniques is presented Thin-layer chromatography (TLC) is used to completely separate acetaminophen and its internal standard from other components (matrix) and to form a single spot/zone containing them at the solvent front position (after the final stage of the thin-layer chromatogram development). The location of the analytes and internal standard in the solvent front zone allows their easy extraction followed by quantitation by HPLC. The exctraction procedure of the solute/s and internal standard can proceed from whole solute frontal zone or its part without lowering in accuracy of quantitative analysis. PMID- 26839179 TI - Poly(2-aminobenzothiazole)-coated graphene oxide/magnetite nanoparticles composite as an efficient sorbent for determination of non-steroidal anti inflammatory drugs in urine sample. AB - In this study, for the first time, 2-aminobenzothiazole monomer was polymerized on Fe3O4 NPs, graphene oxide/Fe3O4 (GO/Fe3O4) and graphene/Fe3O4 (G/Fe3O4) nanocomposites. The synthesized magnetic nanosorbents were characterized by various techniques. The extraction ability of these nanosorbents including Fe3O4, GO/Fe3O4, G/Fe3O4, Fe3O4@poly(2-aminobenzothiazole) (Fe3O4@PABT), GO/Fe3O4@PABT and G/Fe3O4@PABT were compared for dispersive-micro-solid phase extraction of three non-steroidal anti-inflammatory drugs. The results revealed that GO/Fe3O4@PABT nanocomposite demonstrates higher extraction efficiency for naproxen, diclofenac and ibuprofen as selected model analytes. Following the sorption and elution steps, the model analytes were quantified by high performance liquid chromatography-photo diode array detection. Afterwards, a central composite design methodology combined with desirability function approach was applied to find out the optimal experimental conditions. Under the optimized conditions, the limits of detection and linear dynamic ranges were achieved in the range of 0.07-0.3 MUg L(-1) and 0.25-2000 MUg L(-1), respectively. The percent of extraction recovery was 87.4, 85.5 and 90.5% for naproxen, diclofenac and ibuprofen, respectively. The obtained relative standard deviation (n=5) was 7.2, 5.4 and 6.4% for naproxen, diclofenac and ibuprofen, respectively. Ultimately, this method was employed for urinary monitoring of the target analytes and satisfactory results were obtained. PMID- 26839181 TI - Addendum. PMID- 26839182 TI - Automated office blood pressure--the preferred method for recording blood pressure. PMID- 26839183 TI - Auscultatory BP: still the gold standard. AB - 1. Current research documents AusBP is more accurate and reliable than all other clinical methods. 2. All current OBPM devices make large errors in some patients requiring individual validation of accuracy. 3. The only method to detect individual errors is by AusBP. This takes training to mastery of BP measurement skills using our standardized protocol. PMID- 26839180 TI - Depression, suicidal ideation, and related factors of methadone maintenance treatment users in Guangzhou, China. AB - Mental health problems are prevalent among drug users. Methadone maintenance treatment (MMT) is an evidence-based effective treatment for drug addiction; however, there are few studies investigating depression, suicidal ideation, and their related factors among MMT users. In this cross-sectional study, 648 MMT users were recruited from six MMT clinics in Guangzhou, China. Data were collected through face-to-face interviews by trained interviewers. Of all participants, 270 (42.7%) exhibited probable depression (Depression Subscale of the Chinese short version of Depression, Anxiety, and Stress Scale (DASS-D), score >= 10) and 99 (15.3%) reported having suicidal ideation in the last six months. After adjusting for significant socio-demographic characteristics, all studied variables, including drug use history, social support, family support for MMT use, and satisfaction toward MMT services were significantly associated with both probable depression and suicidal ideation in the last six months. Furthermore, depression fully mediated the associations between drug use history, satisfaction toward MMT services, and suicidal ideation. In the final multivariate models, probable depression was associated with social support (OR = 0.88, 95% CI = 0.83-0.93) and satisfaction toward MMT services provided by doctors (OR = 0.59, 95% CI = 0.40-0.86), while for suicidal ideation, social support (OR = 0.85, 95% CI = 0.78-0.92) and probable depression (OR = 5.94, 95% CI = 3.39-10.42) were significant. The findings suggest that there are unmet mental health needs among MMT users. For countries with limited resources of psychological services, mental health care toward MMT users should be implanted into current health care settings and incorporate components such as social support, family's understanding of MMT, and service satisfaction. PMID- 26839184 TI - How should BP be measured in the office? PMID- 26839185 TI - Identification of potential missed opportunities for human papillomavirus (HPV) vaccination in women referred to an academic colposcopy clinic for evaluation of abnormal cervical cytology. AB - OBJECTIVE: To identify possible predictors of missed opportunities for human papillomavirus (HPV) counseling and vaccination prior to presentation at an academic colposcopy clinic. MATERIALS AND METHODS: We examined the characteristics of 638 vaccinated and 1,024 unvaccinated age-eligible patients using data from a patient registry of women presenting for colposcopic evaluation between 2/26/2007 and 3/10/2014 who were aged 26 or less at presentation. Demographics, smoking history, pregnancy history, sexually transmitted infections (STIs), sexual history, contraception use, immunosuppression, and medical problems were compared between HPV vaccinated and unvaccinated women. Multivariable logistic regression models included age, race, language, marital status, insurance type, lifetime number of sexual partners, other medical illnesses, number of pregnancies, contraception use, history of STIs, and smoking history to determine predictors of HPV vaccination. RESULTS: In multivariable analysis, race, marital status, and language were not significantly associated with HPV vaccination. Women with fewer pregnancies were more likely to be vaccinated (p-trend <0 .0001). Vaccinated women were more likely to have other medical illnesses (OR=1.44, 95% CI=1.13-1.83) and be aware of their HPV status (OR=1.75, 95% CI= 1.40-2.18). CONCLUSIONS: In this study, greater number of pregnancies was associated with lower vaccination rates as compared to women who had never been pregnant. Reproductive health visits, such as postpartum and family planning visits, represent an ideal opportunity to educate women about HPV and the importance of vaccination, and should be an area of focus to improve current HPV vaccination rates. PMID- 26839187 TI - Site-Specific Identification of Lysine Acetylation Stoichiometries in Mammalian Cells. AB - Functional characterization of the lysine acetylation pathway requires quantitative measurement of the modification abundance at the stoichiometry level. Here, we developed a systematic workflow for global untargeted identification of site-specific Lys acetylation stoichiometries in mammalian cells. Our strategy includes an optimized protocol for in vitro chemical labeling of unmodified lysine with stable isotope-encoded acetyl-NHS ester, deep proteomic profiling with a high resolution mass spectrometer, and a new software tool for quantitative analysis and stoichiometry determination. The workflow was validated using in vitro chemically labeled BSA and synthetic peptides with multiple Lys acetylations at various positions. In the proof-of-concept study, we applied the strategy to analyze the proteome of HeLa cells and determined the stoichiometries of over 600 acetylation sites with good reproducibility. Sodium butyrate treatment induced a significant increase of acetylation stoichiometries in HeLa cells. Analysis of site-specific stoichiometry dynamics revealed the coregulation of closely positioned acetylation sites on histones H3 and H4 upon treatment. PMID- 26839188 TI - Fluorescent IGF-II analogues for FRET-based investigations into the binding of IGF-II to the IGF-1R. AB - The interaction of IGF-II with the insulin receptor (IR) and type 1 insulin-like growth factor receptor (IGF-1R) has recently been identified as potential therapeutic target for the treatment of cancer. Understanding the interactions of IGF-II with these receptors is required for the development of potential anticancer therapeutics. This work describes an efficient convergent synthesis of native IGF-II and two non-native IGF-II analogues with coumarin fluorescent probes incorporated at residues 19 and 28. These fluorescent analogues bind with nanomolar affinities to the IGF-1R and are suitable for use in fluorescence resonance energy transfer (FRET) studies. From these studies the F19Cou IGF-II and F28Cou IGF-II proteins were identified as good probes for investigating the binding interactions of IGF-II with the IGF-1R and its other high affinity binding partners. PMID- 26839186 TI - A novel Hsp70 inhibitor prevents cell intoxication with the actin ADP ribosylating Clostridium perfringens iota toxin. AB - Hsp70 family proteins are folding helper proteins involved in a wide variety of cellular pathways. Members of this family interact with key factors in signal transduction, transcription, cell-cycle control, and stress response. Here, we developed the first Hsp70 low molecular weight inhibitor specifically targeting the peptide binding site of human Hsp70. After demonstrating that the inhibitor modulates the Hsp70 function in the cell, we used the inhibitor to show for the first time that the stress-inducible chaperone Hsp70 functions as molecular component for entry of a bacterial protein toxin into mammalian cells. Pharmacological inhibition of Hsp70 protected cells from intoxication with the binary actin ADP-ribosylating iota toxin from Clostridium perfringens, the prototype of a family of enterotoxins from pathogenic Clostridia and inhibited translocation of its enzyme component across cell membranes into the cytosol. This finding offers a starting point for novel therapeutic strategies against certain bacterial toxins. PMID- 26839189 TI - Clonal Relationships Between Malignant Lymphomas and Histiocytic/Dendritic Cell Tumors. AB - Tumors of histiocytic or dendritic cell origin appear to occur with increased frequency in patients with lymphoma. Recent molecular data have demonstrated clonal relationships between the lymphoma and the histiocytic/dendritic cell tumor in some of these cases. Clinical, pathologic, and experimental data suggest that this phenomenon probably represents transdifferentiation of the lymphoma clone to a histiocytic/dendritic cell lineage in most cases. Awareness of this entity is necessary to prompt comparative molecular studies in appropriate cases. PMID- 26839190 TI - Distinguishing T-cell Large Granular Lymphocytic Leukemia from Reactive Conditions: Laboratory Tools and Challenges in Their Use. AB - This article focuses on the challenges of diagnosing T-cell large granular leukemia and distinguishing it from benign reactive conditions, as well as more aggressive neoplasms of cytotoxic lymphocytes. No single laboratory method is sufficient to make the diagnosis, but instead a combination of flow cytometry, genetic studies, and bone marrow immunohistochemistry must be used. PMID- 26839191 TI - Erythroleukemia and Its Differential Diagnosis. AB - Acute erythroid leukemias encompass 2 main subtypes: acute erythroleukemia (erythroid/myeloid subtype) and pure erythroid leukemia. This article reviews the main clinicopathologic features of the acute erythroid leukemias and the criteria used to diagnose them. In this article, the differential diagnosis between acute erythroid leukemias and their mimics is discussed and helpful morphologic clues and diagnostic tests that help arrive at the correct diagnosis are provided. The appropriate application of diagnostic criteria, including ancillary testing, such as immunophenotyping, cytogenetics, and molecular genetic testing, is essential to categorize bone marrow erythroid proliferations. PMID- 26839192 TI - Early T-cell Precursor Acute Lymphoblastic Leukemia/Lymphoma. AB - Discrete diagnostic subtypes of T lymphoblastic leukemia/lymphoma (T-cell acute lymphoblastic leukemia/lymphoma, T-ALL) have historically not been widely recognized. Recently, a novel subset with distinctive immunophenotypic, molecular, and clinical features has been proposed. Termed early T-cell precursor acute lymphoblastic leukemia (ETP-ALL), these cases seem to correspond to a very early stage of T-cell development. ETP-ALL is associated with a poor prognosis using standard protocols, and patients with ETP-ALL may benefit from intensified, alternative, or targeted therapies. Recognizing ETP-ALL and distinguishing it from other forms of acute leukemia are important elements of an up-to-date diagnostic approach to precursor T-cell neoplasms. PMID- 26839193 TI - Myeloid Neoplasms with inv(3)(q21q26.2) or t(3;3)(q21;q26.2). AB - Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) [inv3/t(3;3)] is a distinct entity under the subgroup of AMLs with recurrent genetic abnormalities in the 2008 World Health Organization classification. Myelodysplastic syndrome (MDS) with inv3/t(3;3) has a high risk of progression to AML. AML and MDS with inv3/t(3;3) have a similarly aggressive clinical course with short overall survival (OS) and are commonly refractory to therapy. In this article, clinical and pathologic features and prognosis in AML and MDS with inv3/t(3;3) are reviewed, and other myeloid neoplasms with similar dysplastic features to be differentiated from AML and MDS with inv3/t(3;3) are discussed. PMID- 26839194 TI - Update on Myelodysplastic Syndromes Classification and Prognosis. AB - Myelodysplastic syndromes (MDS) are a collection of cytogenetically heterogeneous clonal bone marrow (BM) failure disorders derived from aberrant hematopoietic stem cells in the setting of an aberrant hematopoietic stem cell niche. Patients suffer from variably progressive and symptomatic bone marrow failure with a risk of leukemic transformation. Diagnosis of MDS has long been based on morphologic assessment and blast percentage as in the original French-American-British classification. The recently developed Revised International Prognostic Scoring System provides improved prognostication using more refined cytogenetic, marrow blast, and cytopenia parameters. With the advent of deep sequencing technologies, dozens of molecular abnormalities have been identified in MDS. PMID- 26839195 TI - Atypical Phenotypes in Classical Hodgkin Lymphoma. AB - Classical Hodgkin lymphoma has a characteristic immunophenotype in most cases, with expression of CD30, CD15, and PAX-5, and absence of CD45 and T-lineage markers. However, in a significant subset of cases, atypical staining patterns may be seen for one or more antigens, particularly negative staining for CD15 or staining for one or more B-lineage markers, such as CD20, CD79a, OCT-2, or BOB.1. The greatest pitfall is in the misinterpretation of other cells, such as immunoblasts or histiocytes, as Hodgkin cells. PMID- 26839196 TI - Blastic Plasmacytoid Dendritic Cell Neoplasm: How do You Distinguish It from Acute Myeloid Leukemia? AB - BPDCN is a recently elucidated clinicopathologic entity. This disease typically involves the skin, with 30% to 40% of patients showing an additional concurrent leukemic component. Although BPDCN often exhibits cytologic features akin to acute lymphoblastic leukemia, the main differential diagnostic challenge, in the skin and in the bone marrow, is distinction from AML, in particular AML with monocytic differentiation. PMID- 26839197 TI - The Differential Diagnosis of Eosinophilia in Neoplastic Hematopathology. AB - Eosinophilia in the peripheral blood is classified as primary (clonal) hematologic neoplasms or secondary (nonclonal) disorders, associated with hematologic or nonhematologic disorders. This review focuses on the categories of hematolymphoid neoplasms recognized by the 2008 World Health Organization Classification of Tumours and Haematopoietic and Lymphoid Tissues that are characteristically associated with eosinophilia. We provide a systematic approach to the diagnosis of these neoplastic proliferations via morphologic, immunophenotypic, and molecular-based methodologies, and provide the clinical settings in which these hematolymphoid neoplasms occur. We discuss recommendations that eosinophilia working groups have published addressing some of the limitations of the current classification scheme. PMID- 26839198 TI - Challenges in Consolidated Reporting of Hematopoietic Neoplasms. AB - This article focuses on the challenges of generating comprehensive diagnostic reports in hematopathology. In particular, two main challenges that diagnosticians face are (1) interpreting and understanding the rapid advances in molecular and genetic pathology, which have gained increasing importance in classifications of hematopoietic neoplasms, and (2) managing the logistics of reporting ancillary studies and incorporating them effectively into a final synthesized report. This article summarizes many important genetic findings in hematopoietic neoplasms, which are required for accurate diagnoses, and discusses practical issues to generating accurate and complete hematopathology reports. PMID- 26839201 TI - Why Is Hematopathology so Complicated? PMID- 26839204 TI - Base-Free Direct Synthesis of Alkynylphosphonates from Alkynes and H-Phosphonates Catalyzed by Cu2O. AB - A simple and mild methodology for the direct synthesis of alkynylphosphonates is presented. The reaction of a variety of terminal alkynes with dialkyl phosphites in the presence Cu2O (14 mol %) led to the formation of the corresponding alkynylphosphonates in good to excellent yields. Reactions are performed under air, in acetonitrile as solvent, and in the absence of base or ligand additives. This new methodology is compatible with the presence of a wide variety of functional groups on the starting alkynes and can be scaled up to a gram scale. PMID- 26839205 TI - Gastric hemorrhage after ingestion of a blister-wrapped tablet. PMID- 26839207 TI - Pharmacokinetics of TAK-475, a Squalene Synthase Inhibitor, in Rats and Dogs. AB - The pharmacokinetics of TAK-475 (lapaquistat acetate), a squalene synthase inhibitor, was investigated in rats and dogs. After oral administration of (14)C labeled TAK-475 ([(14)C]TAK-475) to rats and dogs at a dose of 10 mg/kg, the bioavailability (BA) was relatively low at 3.5 and 8.2%, respectively. The main component of the radioactivity in the plasma was M-I, which has a comparable pharmacological activity to TAK-475 in vitro. The radioactivity in the portal plasma after intraduodenal administration of [(14)C]TAK-475 to portal vein cannulated rat was also mainly M-I, suggesting that most of the TAK-475 was hydrolyzed to M-I during the permeable process in the intestine. The concentrations of M-I in the liver, the main organ of cholesterol biosynthesis, were much higher than those in the plasma after oral administration of [(14)C]TAK 475 to rats. The main elimination route of the radioactivity was fecal excretion after oral administration of [(14)C]TAK-475 to rats and dogs, and the absorbed radioactivity was mainly excreted via the bile as M-I in rats. M-I excreted into the bile was partially subjected to enterohepatic circulation. These results suggest that although the BA values of TAK-475 are low, M-I can exert compensatory pharmacological effects in the animals. These pharmacokinetic characteristics in animals were also confirmed in the clinical studies. The evaluation of M-I disposition is important for the pharmacokinetics, pharmacodynamics and toxicity of TAK-475 in animals and humans. PMID- 26839206 TI - [Drug-induced acute pancreatitis]. PMID- 26839208 TI - Prediction of congenital hypothyroidism based on initial screening thyroid stimulating-hormone. AB - BACKGROUND: In thyroid-stimulating-hormone (TSH)-based newborn congenital hypothyroidism (CH) screening programs, the optimal screening-TSH cutoff level is critical to ensuring that true cases of CH are not missed. Screening-TSH results can also be used to predict the likelihood of CH and guide appropriate clinical management. The purpose of this study is to evaluate the predictive value of various screening-TSH levels in predicting a diagnosis of CH in the Ontario Newborn Screening Program (ONSP). METHODS: The initial screening and follow-up data of 444,744 full term infants born in Ontario, Canada from April 1, 2006 to March 31, 2010 were analyzed. Confirmed CH cases were based on local endocrinologists' report and initiation of thyroxine treatment. RESULTS: There were a total of 541 positive screening tests (~1/822 live births) of which 296 were true positives (~1:1,500 live births). Subjects were further subdivided based on screening-TSH and positive predictive values (PPV) were calculated. Twenty four percent in the 17-19.9 mIU/L range were true positives. In the 17-30 mIU/L range, 29 % were true positives with a significantly higher PPV for those sampled after (43 %) rather than before (25 %) 28 h of age (p < 0.02). Seventy three percent of neonates with an initial screening-TSH of >= 30 mIU/L and 97 % of those with >= 40 mIU/L were later confirmed to have CH. CONCLUSIONS: Infants with modestly elevated screening positive TSH levels between 17 and 19.9 mIU/L have a significant risk (24 %) of having CH. The very high frequency of true positives in term newborns with initial TSH values >= 30mIU/L suggests that this group should be referred directly to a pediatric endocrinologist in an effort to expedite further assessment and treatment. Screen positives with a modestly elevated TSH values (17-19.9 mIU/L) need to be examined in more detail with extended follow-up data to determine if they have transient or permanent CH. PMID- 26839209 TI - Controllable band structure and topological phase transition in two-dimensional hydrogenated arsenene. AB - Discovery of two-dimensional (2D) topological insulator such as group-V films initiates challenges in exploring exotic quantum states in low dimensions. Here, we perform first-principles calculations to study the geometric and electronic properties in 2D arsenene monolayer with hydrogenation (HAsH). We predict a new sigma-type Dirac cone related to the px,y orbitals of As atoms in HAsH, dependent on in-plane tensile strain. Noticeably, the spin-orbit coupling (SOC) opens a quantum spin Hall (QSH) gap of 193 meV at the Dirac cone. A single pair of topologically protected helical edge states is established for the edges, and its QSH phase is confirmed with topological invariant Z2 = 1. We also propose a 2D quantum well (QW) encapsulating HAsH with the h-BN sheet on each side, which harbors a nontrivial QSH state with the Dirac cone lying within the band gap of cladding BN substrate. These findings provide a promising innovative platform for QSH device design and fabrication operating at room temperature. PMID- 26839210 TI - Minimally invasive endoscopic repair of atrial septal defects via right minithoracotomy. AB - Atrial septal defect (ASD) repair has been conventionally performed via midline sternotomy with very low operative risk and excellent early and late outcomes. Recently, many of these patients with suitable anatomy are being treated with percutaneous catheter-based closure of their ASD, but issues of prosthetic device implantation, long-term antiplatelet therapy and late device complications persist. Minimally invasive repair of ASD via a 3-cm right minithoracotomy provides patients with a much less invasive surgical repair with all the durable benefits of autologous pericardial patch closure. However, widespread adoption of the minithoracotomy approach to ASD closure remains slow. This study describes the simple steps to ASD repair via a right minithoracotomy. PMID- 26839212 TI - Prevailing Trends in Haptic Feedback Simulation for Minimally Invasive Surgery. AB - Background The amount of direct hand-tool-tissue interaction and feedback in minimally invasive surgery varies from being attenuated in laparoscopy to being completely absent in robotic minimally invasive surgery. The role of haptic feedback during surgical skill acquisition and its emphasis in training have been a constant source of controversy. This review discusses the major developments in haptic simulation as they relate to surgical performance and the current research questions that remain unanswered. Search Strategy An in-depth review of the literature was performed using PubMed. Results A total of 198 abstracts were returned based on our search criteria. Three major areas of research were identified, including advancements in 1 of the 4 components of haptic systems, evaluating the effectiveness of haptic integration in simulators, and improvements to haptic feedback in robotic surgery. Conclusions Force feedback is the best method for tissue identification in minimally invasive surgery and haptic feedback provides the greatest benefit to surgical novices in the early stages of their training. New technology has improved our ability to capture, playback and enhance to utility of haptic cues in simulated surgery. Future research should focus on deciphering how haptic training in surgical education can increase performance, safety, and improve training efficiency. PMID- 26839211 TI - How to unveil self-quenched fluorophores and subsequently map the subcellular distribution of exogenous peptides. AB - Confocal laser scanning microscopy (CLSM) is the most popular technique for mapping the subcellular distribution of a fluorescent molecule and is widely used to investigate the penetration properties of exogenous macromolecules, such as cell-penetrating peptides (CPPs), within cells. Despite the membrane-association propensity of all these CPPs, the signal of the fluorescently labeled CPPs did not colocalize with the plasma membrane. We studied the origin of this fluorescence extinction and the overall consequence on the interpretation of intracellular localizations from CLSM pictures. We demonstrated that this discrepancy originated from fluorescence self-quenching. The fluorescence was unveiled by a "dilution" protocol, i.e. by varying the ratio fluorescent/non fluorescent CPP. This strategy allowed us to rank with confidence the subcellular distribution of several CPPs, contributing to the elucidation of the penetration mechanism. More generally, this study proposes a broadly applicable and reliable method to study the subcellular distribution of any fluorescently labeled molecules. PMID- 26839213 TI - Postmarketing Analysis of a Novel, Cordless Ultrasonic Dissector. AB - Introduction Tissue dissection and vessel sealing is performed using a variety of energy sources and surgical devices. We describe the postmarketing analysis of a cordless ultrasonic dissector and vessel sealer in a series of general and gynecological procedures. Methods Patients were prospectively screened and consented for participation. Data collected included demographics, device activations/seals and failures, and patient complications. Surgeons were surveyed following each case. Data was analyzed using standard statistical methods. Results A total of 110 patients were consented and participated in the study. The most frequently performed procedures were bilateral salpingo-oophorectomy (n = 48) and total laparoscopic hysterectomy (n = 36). Mean age was 54.2 years and 79.2% were female. The most frequent number of device activations per case was between 26 and 50 (36.6%). Five failed seals occurred out of 4858 total estimated seals (0.11%). Failed seals were felt to be due to thickened, scarred tissue not amenable to device compression. There were no patient intraoperative complications related to the device itself. Overall, surgeons felt the device was extremely easy to use (97.6%) and no visual obstruction due to steam from the device was encountered (95%). Ninety-five percent of surgeons felt the device was beneficial for soft tissue dissection and vessel sealing. Conclusion Sonicision is safe and effective for use in dissection of soft tissues and vessel sealing in a variety of laparoscopic and open procedures. In this study, there were no complications related to the device itself. The remarkable cordless design of this device enhances its ease of use with overall excellent effectiveness. PMID- 26839214 TI - Safety and Feasibility of Laparoscopic Abdominal Surgery in Patients With Mechanical Circulatory Assist Devices. AB - Objectives Increasing number of mechanical circulatory assist devices (MCADs) are being placed in heart failure patients. Morbidity from device placement is high and the outcome of patients who require noncardiac surgery after, is unclear. As laparoscopic interventions are associated with decreased morbidity, we examined the impact of such procedures in these patients. Methods A retrospective review was conducted on 302 patients who underwent MCAD placement from 2005 to 2012. All laparoscopic abdominal surgeries were included and impact on postoperative morbidity and mortality studied. Results Ten out of 16 procedures were laparoscopic with 1 conversion to open. Seven patients had a HeartMate II, 2 had Total Artificial Hearts, and 1 had CentriMag. Four patients had devices for ischemic cardiomyopathy and 6 cases were emergent. Surgeries included 6 laparoscopic cholecystectomies, 2 exploratory laparoscopies, 1 laparoscopic colostomy takedown, and 1 laparoscopic ventral hernia repair with mesh. Median age of the patients was 63 years (range, 29-79 years). Median operative time was 123 minutes (range, 30-380 minutes). Five of 10 patients were on preoperative anticoagulation with average intraoperative blood loss of 150 mL (range, 20-700 mL). There were 3 postoperative complications; acute respiratory failure, acute kidney injury and multisystem organ failure resulting in death not related to the surgical procedure. Conclusion The need for noncardiac surgery in post-MCAD patients is increasing due to limited donors and due to more durable and longer support from newer generation assist devices. While surgery should be approached with caution in this high-risk group, laparoscopic surgery appears to be a safe and successful treatment option. PMID- 26839215 TI - Initial Experience of Multivision Thoracoscopic Surgery With Two Cameras: Dual Vision VATS. PMID- 26839218 TI - Key enzymes behind black pepper aroma in wines. PMID- 26839219 TI - How can we breed for more water use-efficient sugarcane? PMID- 26839216 TI - A Cross-Species Study of PI3K Protein-Protein Interactions Reveals the Direct Interaction of P85 and SHP2. AB - Using a series of immunoprecipitation (IP)-tandem mass spectrometry (LC-MS/MS) experiments and reciprocal BLAST, we conducted a fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome in a drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. Using H929 human cancer cells and drosophila S2R+ cells, our data revealed an unexpected direct binding of Corkscrew, the drosophila ortholog of the non-receptor protein tyrosine phosphatase type II (SHP2) to the Pi3k21B (p60) regulatory subunit of PI3K (p50/p85 human ortholog) but no association with Pi3k92e, the human ortholog of the p110 catalytic subunit. The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (GAB2). Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. A disruption of the SHP2-p85 complex took place after insulin/IGF1 stimulation or imatinib treatment, suggesting that the direct SHP2-p85 interaction was both independent of AKT activation and positively regulates the ERK signaling pathway. PMID- 26839220 TI - Nitric oxide signalling in a CO2-enriched environment. PMID- 26839221 TI - Pediatric Vascular Tumors and Malformations. AB - Pediatric vascular tumors and malformations, comprising a broad category of lesions often referred to as vascular anomalies, are a heterogenous group of clinicopathologically distinct entities. Pathologists, clinicians, and radiologists have traditionally lumped these lesions under the generic term, hemangioma, sometimes qualified by modifiers, such as capillary or cavernous. Advances in understanding underlying pathogenetic mechanisms support more specific classification and more specifically targeted therapies. Multidisciplinary consensus has moved toward a biologically based classification system and therapeutic approach for dealing with these lesions. This content focuses on the histologic, immunophenotypical, and clinical features that distinguish the major types of vascular tumors and malformations presenting in infancy and childhood. Pathogenic mechanisms are also briefly reviewed. PMID- 26839222 TI - New Entities and Diagnostic Challenges in Pediatric Lung Disease. AB - The differential diagnosis of diffuse lung disease in children differs considerably from adults, and analysis of pediatric lung biopsies may prove challenging for pathologists with more extensive exposure to adult lung biopsies. Biopsy diagnosis of pediatric lung disease continues to evolve as new pathologic entities are recognized and new genetic determinants of disease are discovered. This article describes the clinical characteristics, pathologic features, and differential diagnosis of challenging and recently described entities in pediatric lung disease. The specific entities discussed include alveolar capillary dysplasia, genetic disorders of surfactant metabolism, pulmonary interstitial glycogenosis, and neuroendocrine cell hyperplasia of infancy. PMID- 26839223 TI - Modern Diagnosis of Small Cell Malignancies of Children. AB - Small cell malignancies of children constitute a continuing diagnostic challenge for surgical pathologists, although modern methods of ancillary diagnosis provide powerful tools that resolve most difficult cases. Current techniques range from identification of DNA alternations, including gene fusions, chromosome translocations, and genetic deletions, to recognition of characteristic patterns of protein expression, usually visualized with immunohistochemistry. In spite of these advances, recognition of key cellular and histologic features remains the keystone of diagnosis but requires adequately fixed and carefully stained histologic sections. Cytologic features now suffice for diagnosis if confirmed by appropriate testing. This article outlines key histologic features of pediatric small cell neoplasms and the algorithms that allow diagnostic confirmation and the initiation of appropriate therapy. PMID- 26839224 TI - Disorders of Sexual Differentiation. AB - The term, disorders of sexual differentiation, broadly represents a disjunction between genotype and phenotype. Phenotype in turn can refer to external or internal genital development. Disorders of sexual differentiation are determined at conception insofar as (1) the abnormal genotype is the aberrant genetic product of fertilization at the chromosomal level or (2) the abnormal phenotype results from postfertilization errors in function at the gene level, somewhere along the pathway of transcription and translation. In either event, the error is genetic, whether or not sporadic or inherited, even if the pathways have yet to be fully elucidated for a given disorder. PMID- 26839225 TI - Enteropathies of Infancy and Childhood. AB - Intestinal biopsies constitute an ever-increasing portion of the pathologist's workload, accounting for nearly two-thirds of specimens accessioned yearly by the pathology department at The Children's Hospital of Philadelphia. The widespread use of endoscopy and gastrointestinal biopsies in current clinical practice presents the pathologist with a diversity of intestinal mucosal appearances corresponding to disease states of variable clinical severity, requiring close collaboration between clinician and pathologist for optimal interpretation. Many of the entities resulting in severe diarrhea of infancy have been recognized only in the last several decades, and although rare, the study of these disorders, especially when combined with the powerful methods of present-day genetics and molecular biology, has afforded important insights into enterocyte development and function, and intestinal immunity and tolerance. Other conditions once considered infrequent, such as celiac disease, have now been recognized to be much more common and can present with a wide range of pathologic features. PMID- 26839226 TI - Myofibroblastic Tumors in Children. AB - Pediatric myofibroblastic tumors comprise a clinically and pathologically heterogeneous group of neoplasms, including benign tumors, those of intermediate biologic potential, and frankly malignant examples (Box 1). Proper classification is critical for appropriate prognostication, clinical management, and, in some cases, identification of familial syndromes. Unlike for many other soft tissue tumors, immunohistochemistry plays a limited role in the diagnosis of pediatric myofibroblastic tumors, with notable exceptions. Understanding the molecular genetics underlying the pathogenesis of several tumor types in this group has led to improved tools for diagnosis. This article discusses the clinical and pathologic features of myofibroblastic tumors in children, with special emphasis on differential diagnosis. PMID- 26839227 TI - Childhood Carcinoma. AB - Carcinoma in children differs from that occurring in adults. It is far rarer and represents only a small fraction of all pediatric cancer diagnoses. Pediatric sarcomas were among the first tumors in which recurrent chromosomal aberrations were discovered. Once defined, these recurrent aberrations, many of them translocations, became incorporated into the pathologist's diagnostic armamentarium. In the past several years, defining chromosomal rearrangements have been identified in pediatric carcinomas as well, and this has become a new frontier in pathologic diagnosis. This article provides an overview of pediatric carcinoma as well as a detailed review of selected types of carcinoma that in particular can present diagnostic difficulty to the practicing pathologist and illustrate new and emerging concepts in pediatric carcinoma. PMID- 26839228 TI - Pathology of Intestinal Motor Disorders in Children. AB - Varied intestinal neuromuscular pathologies are responsible for Hirschsprung disease and other forms of chronic pseudo-obstruction that are encountered in pediatrics. Pathologically distinct subtypes discussed in this review include aganglionosis, hypoganglionosis, neuronal intranuclear inclusion disease, ganglionitis, degenerative neuropathy, diffuse ganglioneuromatosis, neuronal dysplasia, malformations of the muscularis propria, degenerative leiomyopathy, leiomyositis, and mitochondriopathies. Emphasis is given to the histopathologic features that distinguish these conditions and their differential diagnoses. PMID- 26839229 TI - Biopsy Diagnosis of Inherited Liver Disease. AB - Hepatic dysfunction during childhood can be due to acquired or inherited etiologies or a combination. The distinction can be difficult to make on liver biopsy, because the inherited disorders are rare and often lack pathognomonic light microscopic features. Recent progress in understanding the pathogenesis of these disorders has led to advances in molecular genetic screening and confirmatory tests. For a majority of these disorders, the liver biopsy continues to play a crucial role in primary diagnosis or confirmation. This article discusses algorithms that may aid pathologists in differential diagnosis of common inherited disorders of the liver, with emphasis on ancillary diagnostic tools and reference assays that are critical in establishing the diagnosis. PMID- 26839230 TI - Frozen Section Diagnosis of Pediatric Brain Tumors. AB - Brain tumors represent a significant group of tumors seen in the pediatric population. Intraoperative consultation represents a critical and integral component of the management of these tumors. Since the prevalence, frequency, and location of the different histologic types of brain tumors vary significantly between children and adults, it is reasonable to expect that diagnoses entertained during intraoperative consultation will also differ, influencing the aggressiveness of surgical resection and course of management. It is, therefore, imperative for surgical pathologists responsible for pediatric patients to become familiar with these entities and the diagnostic challenges they pose during the course of surgery. PMID- 26839231 TI - Diagnosis in Pediatric Transplant Biopsies. AB - Infant recipients have better survival after solid organ transplantation than older children and adults possibly due to immune tolerance. Over the past two decades, postsurgical complications have markedly decreased, and multidrug immunosuppressive regimens have become effective in preventing and treating rejection. Immunocompromised for life, these patients are susceptible to both the usual bacterial as well as opportunistic infections that often involve the lung. Post-transplant lymphoproliferative disease seems to be decreasing even further in frequency. This article focuses on the findings seen on biopsy, usually of the transplanted organ, and also of other sites affected by post-transplant complications. PMID- 26839232 TI - Pediatric Pathology: Diagnosis at the Intersection of Genetics, Embryology, and Histology. PMID- 26839233 TI - Atypical epidermoid cyst containing multiple nail plates at a finger amputation stump. PMID- 26839234 TI - Causes of secondary deformity after surgery to correct Wassel type IV-D thumb duplication. AB - This study was undertaken to document the causes of secondary deformities after surgery for correction of Wassel type IV-D thumb duplication. We carefully dissected and observed the flexor pollicis longus, and bone and joint anatomy in eight patients with secondary deformities after surgical correction. We transferred the flexor pollicis longus and thenar muscle attachments, reconstructed the A2 pulley, released and tightened the joint capsule, and performed osteotomies to correct skeletal malalignment. Kirschner wire fixation was used for 4-5 weeks, followed by brace fixation for 3 months. Patients were followed up for 13-34 months (mean 20 months). According to the Tada scores, the outcomes were good in six patients, and fair and poor in one patient each. The main causes of the secondary deformities were failure to reconstruct the A2 pulley, to transfer the flexor pollicis longus and thenar muscles, and incomplete resection of the radial metacarpal head. Brace fixation after Kirschner wire removal is crucial in preventing secondary deformities. LEVEL OF EVIDENCE: IV. PMID- 26839236 TI - Allocating Deceased Donor Kidneys to Sensitized Candidates. PMID- 26839235 TI - Allocating Deceased Donor Kidneys to Candidates with High Panel-Reactive Antibodies. AB - BACKGROUND AND OBJECTIVES: In December of 2014, the Organ Procurement and Transplant Network implemented a new Kidney Allocation System (KAS) for deceased donor transplant, with increased priority for highly sensitized candidates (calculated panel-reactive antibody [cPRA] >99%). We used a modified version of the new KAS to address issues of access and equity for these candidates. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a simulation, 10,988 deceased donor kidneys transplanted into waitlisted recipients in 2010 were instead allocated to candidates with cPRA>=80% (n=18,004). Each candidate's unacceptable donor HLA antigens had been entered into the allocation system by the transplant center. In simulated match runs, kidneys were allocated sequentially to adult ABO identical or permissible candidates with cPRA 100%, 99%, 98%, etc. to 80%. Allocations were restricted to donor/recipient pairs with negative virtual crossmatches. RESULTS: The simulation indicated that 2111 of 10,988 kidneys (19.2%) would have been allocated to patients with cPRA 100% versus 74 of 10,988 (0.7%) that were actually transplanted. Of cPRA 100% candidates, 74% were predicted to be compatible with an average of six deceased donors; the remaining 26% seemed to be incompatible with every deceased donor organ that entered the system. Of kidneys actually allocated to cPRA 100% candidates in 2010, 66% (49 of 74) were six antigen HLA matched/zero-antigen mismatched (HLA-A, -B, and -DR) with their recipients versus only 11% (237 of 2111) in the simulation. The simulation predicted that 10,356 of 14,433 (72%) candidates with cPRA 90%-100% could be allocated an organ compared with 7.3% who actually underwent transplant. CONCLUSIONS: Data in this simulation are consistent with early results of the new KAS; specifically, nearly 20% of deceased donor kidneys were (virtually) compatible with cPRA 100% candidates. Although most of these candidates were predicted to be compatible with multiple donors, approximately one-quarter are unlikely to receive a single offer. PMID- 26839238 TI - Morphology of tributaries of coronary sinus in humans - corrosion casting study. AB - The study was carried out on 80 human hearts obtained during autopsies. The vascular beds were filled with synthetic resin and next corroded. In all 80 hearts we have been found both: great, middle and small cardiac veins. In two out of 80 hearts we did not find oblique vein of the left atrium. Posterior vein of the left ventricle was double in four hearts. Right marginal vein was found in 5 hearts, left marginal vein was seen in 9 hearts. We also compared the dimensions of all of the above mentioned tributaries of the coronary sinus. PMID- 26839237 TI - Amyloid beta-Protein Assembly and Alzheimer's Disease: Dodecamers of Abeta42, but Not of Abeta40, Seed Fibril Formation. AB - Evidence suggests that oligomers of the 42-residue form of the amyloid beta protein (Abeta), Abeta42, play a critical role in the etiology of Alzheimer's disease (AD). Here we use high resolution atomic force microscopy to directly image populations of small oligomers of Abeta42 that occur at the earliest stages of aggregation. We observe features that can be attributed to a monomer and to relatively small oligomers, including dimers, hexamers, and dodecamers. We discovered that Abeta42 hexamers and dodecamers quickly become the dominant oligomers after peptide solubilization, even at low (1 MUM) concentrations and short (5 min) incubation times. Soon after (>=10 min), dodecamers are observed to seed the formation of extended, linear preprotofibrillar beta-sheet structures. The preprotofibrils are a single Abeta42 layer in height and can extend several hundred nanometers in length. To our knowledge this is the first report of structures of this type. In each instance the preprotofibril is associated off center with a single layer of a dodecamer. Protofibril formation continues at longer times, but is accompanied by the formation of large, globular aggregates. Abeta40, by contrast, does not significantly form the hexamer or dodecamer but instead produces a mixture of smaller oligomers. These species lead to the formation of a branched chain-like network rather than discrete structures. PMID- 26839239 TI - Awareness of cardiovascular risk factors in ambulatory cardiology patients. AB - Cardiovascular diseases (CVD) are the leading cause of mortality. The majority of CVD risk factors are modifiable and controllable so the knowledge of them might prevent circulatory diseases development and improve already diagnosed CVD outcomes. The aim of the study was to assess the awareness of risk factors for CVD in ambulatory patients of cardiology offices. A specially designed questionnaire was used by trained physicians in a structured technique of face-to face interview in 284 consecutive patients (men - 47.9%, aged 64.1 +/- 11.2 years). As many as 6.3% of the study participants did not name any CVD risk factor, whereas only 7.4% of patients knew at least 3 of them. Smoking and high cholesterol were best recognized (33.1% and 27.4%, respectively) while the least often quoted old age was identified only by 2.5% of the individuals. The average number of the listed CVD risk factors equaled 1.38 +/- 0.77. In the multiple regression analysis the factors significantly associated with knowledge of CVD risk factors comprised the level of education (b = 0.55, p < 0.0001) and age (b = -0.02, p < 0.0001). The patients with family history of CVD diseases were more often aware of the fact that family history of CVD is a risk factor for CVD as compared to individuals with no relatives affected by CVD (21.9% vs 10.1%, p = 0.0061). To the contrary, respondents with hypercholesterolemia less often knew that dyslipidemia is a CVD risk factor than patients with normal cholesterol levels (24.1% vs 41.1%, p = 0.0108). In conclusion, the awareness of cardiovascular risk factors in ambulatory cardiology patients is very low. The perception of CVD risk factors is affected by the level of education and age. PMID- 26839240 TI - Main health-related quality-of-life issues in patients after a distal radius fracture. AB - AIM: The aim of this study was to identify and assess the degree and clinical course of the main health-related quality-of-life (HRQoL) issues in patients after a distal radius fracture (DRF). MATERIALS AND METHODS: Patients were eligible if they were between 18-80 years and were within 1-3 days after a non comminuted DRF. All patients filled out the Polish version of the IOF QLQ, the SF 36 and a demographic questionnaire. Assessment points were set as soon as possible after the fracture, 7 days, 6 weeks, 3 months, and 6 after the fracture. Standard statistical analyses were performed. RESULTS: During the 16 month recruitment period a total of 71 patients (55 women - 77.5%), with a mean age of 64.1 +/- 12.4 years, were included in the study group. All patients suffered from Colles type fractures. Attrition to follow-up was acceptable. At baseline, basing on the IOF QLQ scale scores, DRF patients had the most significant problems with physical function (82.8/100; with 100 representing the worst possible HRQoL), and general health (78.1/100). Basing on SF-36 scale scores patients most significant problems were associated with role limitations due to physical health problems (15.1/100; with 100 representing the best possible HRQoL), and bodily pain (39.5/100). CONCLUSIONS: Concluding, this study shows that the main issues with which patients with and extra-articular DRF struggle the most are pain of the fractured extremity and physical dysfunction. These symptoms are most pronounced in the early post-injury period, and in the majority of patients steadily decrease over a period of six months. PMID- 26839241 TI - Application of the temporal bone for sex determination from the skeletal remains. AB - This paper presents state of current knowledge on possibilities and accuracy of sex determination from the temporal bone. Experimental and comparative studies performed on temporal bones derived from different human populations allowed to verify to what extend this bone is valuable source of information on sex of individual. It was figured out that the temporal bone can be used for this purpose and the size of the mastoid process is considered to be one of the best sex discriminator. PMID- 26839242 TI - Histological and immunohistochemical features of medullary breast cancer. AB - Disputes take place among many scientists about the position of MC in the classification of breast cancer. Some say that this kind of tumor is a sign of invasive ductal carcinoma (IDC). Instead, most of modern researchers distinguish MC of the breast as a separate nosological unit. Primarily there were selected 20 cases of MC and 10 cases of IDC (as control group). The immunohistochemical study revealed the presence of ER, PR, HER2/neo, p53, Ki-67, MMP1 and E-cadherin receptors. In the study of receptor status of tumors it was observed that 100% of MC cases were estrogen-, progesterone- and HER2/ neu negative. The status of tumors on receptor p53 and Ki-67 was as follows: p53+ status had 80% and Ki-67+ had 85% of tissues of MC. In 75% of cases MC cells expressed marker of adhesion and in 100% of cases cells were receptor-negative for expression of MMP1. The data of the study show that the invasive ductal carcinoma and medullary carcinoma are completely independent and different types of malignancy in the breast. The favorable behavior of medullary cancer is associated with expression of E cadherin receptors, which are essentially adhesion factor and absence of MMP1 which are factors of metastatic potential of the tumor. PMID- 26839243 TI - Non-steroidal anti-inflammatory drugs and paracetamol in self-therapy of various disorders in students of different fields of study. AB - Over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol are most commonly the first-line pharmacotherapy in combating different pain and inflammatory disorders and fever. Unfortunately, those drugs might have serious side effects, especially when they are used in an inappropriate way. The aim of the study was to explore various aspects of NSAIDs and paracetamol use in the self-therapy of miscellaneous disorders in young adults. The questionnaire-based survey comprised 250 consecutive students aged 22.1 +/- 1.9 years (189 women) of diverse fields of study. The drugs were applied in clinical conditions in which they should be avoided including asthma attack (1.2%), vomiting (2.4%), malaise and depression (3.6%), in autumn and winter as a preventive measure against infections (14.0%), heart-burn (2.0%) and during food poisoning (16.0%). As many as 6.0% of the students claimed that studied medications are ultimately free of adverse reactions. Men more frequently than women used NSAIDs and paracetamol during alcohol consumption (49.2% vs 30.7%, p = 0.009, respectively) but less often were aware that there are maximum doses of medications which should not be exceeded (57.4% vs 76.7%, p = 0.003, respectively). The students of medical related degree courses (n = 82) compared with individuals of other subjects (n = 168) declared they more often have the custom of always reading medications' leaflets (46.3% vs 31.0%, p = 0.017, respectively). Side effects of medicines were reported by 65 participants - 26.0%. In conclusion, students' knowledge about NSAIDs and paracetamol is low. Participants do not search for information on drug related endangerments, the medication group choice for the given disorder is often inappropriate and the drugs are applied in conditions in which they are contraindicated. PMID- 26839244 TI - Clinical course of primary sclerosing cholangitis and concomitant ulcerative colitis - a preliminary report of retrospective study among patients from Southern Poland. AB - Both ulcerative colitis (UC) and primary sclerosing cholangitis (PSC) are chronic and progressive diseases of uncertain etiology, that may affect one patient. Approximately 70% of PSC cases are also diagnosed with UC, whereas in the group of UC the prevalence of PSC is about 2-5%. The aim of the study was to compare clinical courses of PSC and UC in patients diagnosed with both diseases to those with the confirmed diagnosis of either PSC or UC. Three groups were distinguished and evaluated: patients with PSC and UC (n = 17) and two control groups: patients with PSC (n = 4) and with UC (n = 13). Clinical data, symptoms, laboratory tests, results of the magnetic resonance cholangiopancreatography and colonoscopy were analyzed to compare clinical courses of these diseases between the groups. CONCLUSION: there is no correlation between clinical course of simultaneous PSC and UC. However, it may differ depending on co-occurrence of the other disease. PMID- 26839245 TI - The non-motor complications in Parkinson's disease - what can we learn from animal models? AB - Sporadic Parkinson's disease is a widespread human disease that has never been reported in non-human vertebrates. The etiopathogenesis of the non-motor symptoms in the disease is not well understood and it is difficult to interpret the roles of affected neurotransmitters in currently available animal models. Most of the non-motor symptoms do not correlate with the stage of motor deficits and precede the development of motor symptoms by many years, before the permanent loss of dopaminergic neurons in the basal ganglia. The aim of this review is to briefly summarize the advantages and limitations of the well-recognized mammalian animal models with special regard to the non-motor complications of the prodromal and early stage Parkinson's disease. PMID- 26839247 TI - Zika virus is a global public health emergency, declares WHO. PMID- 26839249 TI - Erratum. PMID- 26839246 TI - Marine mammals harbor unique microbiotas shaped by and yet distinct from the sea. AB - Marine mammals play crucial ecological roles in the oceans, but little is known about their microbiotas. Here we study the bacterial communities in 337 samples from 5 body sites in 48 healthy dolphins and 18 healthy sea lions, as well as those of adjacent seawater and other hosts. The bacterial taxonomic compositions are distinct from those of other mammals, dietary fish and seawater, are highly diverse and vary according to body site and host species. Dolphins harbour 30 bacterial phyla, with 25 of them in the mouth, several abundant but poorly characterized Tenericutes species in gastric fluid and a surprisingly paucity of Bacteroidetes in distal gut. About 70% of near-full length bacterial 16S ribosomal RNA sequences from dolphins are unique. Host habitat, diet and phylogeny all contribute to variation in marine mammal distal gut microbiota composition. Our findings help elucidate the factors structuring marine mammal microbiotas and may enhance monitoring of marine mammal health. PMID- 26839251 TI - Building a better nanopore. PMID- 26839250 TI - Statin and Aspirin Use and the Risk of Mood Disorders among Men. AB - BACKGROUND: There is a growing understanding that depression is associated with systemic inflammation. Statins and aspirin have anti-inflammatory properties. Given these agents have been shown to reduce the risk of a number of diseases characterized by inflammation, we aimed to determine whether a similar relationship exists for mood disorders (MD). METHODS: This study examined data collected from 961 men (24-98 years) participating in the Geelong Osteoporosis Study. MD were identified using a semistructured clinical interview (SCID-I/NP). Anthropometry was measured and information on medication use and lifestyle factors was obtained via questionnaire. Two study designs were utilized: a nested case-control and a retrospective cohort study. RESULTS: In the nested case control study, exposure to statin and aspirin was documented for 9 of 142 (6.3%) cases and 234 of 795 (29.4%) controls (P < .001); after adjustment for age, exposure to these anti-inflammatory agents was associated with reduced likelihood of MD (OR 0.2, 95%CI 0.1-0.5). No effect modifiers or other confounders were identified. In the retrospective cohort study of 836 men, among the 210 exposed to statins or aspirin, 6 (2.9%) developed de novo MD during 1000 person-years of observation, whereas among 626 nonexposed, 34 (5.4%) developed de novo MD during 3071 person-years of observation. The hazard ratio for de novo MD associated with exposure to anti-inflammatory agents was 0.55 (95%CI 0.23-1.32). CONCLUSIONS: This study provides both cross-sectional and longitudinal evidence consistent with the hypothesis that statin and aspirin use is associated with a reduced risk of MD. PMID- 26839248 TI - Stimulated Raman scattering microscopy: an emerging tool for drug discovery. AB - Optical microscopy techniques have emerged as a cornerstone of biomedical research, capable of probing the cellular functions of a vast range of substrates, whilst being minimally invasive to the cells or tissues of interest. Incorporating biological imaging into the early stages of the drug discovery process can provide invaluable information about drug activity within complex disease models. Spontaneous Raman spectroscopy has been widely used as a platform for the study of cells and their components based on chemical composition; but slow acquisition rates, poor resolution and a lack of sensitivity have hampered further development. A new generation of stimulated Raman techniques is emerging which allows the imaging of cells, tissues and organisms at faster acquisition speeds, and with greater resolution and sensitivity than previously possible. This review focuses on the development of stimulated Raman scattering (SRS), and covers the use of bioorthogonal tags to enhance sample detection, and recent applications of both spontaneous Raman and SRS as novel imaging platforms to facilitate the drug discovery process. PMID- 26839252 TI - Enhancing nanopore sensing with DNA nanotechnology. PMID- 26839254 TI - Towards a new scale. PMID- 26839253 TI - The promises and challenges of solid-state sequencing. PMID- 26839256 TI - 2D superconductivity: Electric tuning of many-body states. PMID- 26839259 TI - Learning from peer review. PMID- 26839257 TI - Decoding DNA, RNA and peptides with quantum tunnelling. AB - Drugs and treatments could be precisely tailored to an individual patient by extracting their cellular- and molecular-level information. For this approach to be feasible on a global scale, however, information on complete genomes (DNA), transcriptomes (RNA) and proteomes (all proteins) needs to be obtained quickly and at low cost. Quantum mechanical phenomena could potentially be of value here, because the biological information needs to be decoded at an atomic level and quantum tunnelling has recently been shown to be able to differentiate single nucleobases and amino acids in short sequences. Here, we review the different approaches to using quantum tunnelling for sequencing, highlighting the theoretical background to the method and the experimental capabilities demonstrated to date. We also explore the potential advantages of the approach and the technical challenges that must be addressed to deliver practical quantum sequencing devices. PMID- 26839258 TI - Graphene nanodevices for DNA sequencing. AB - Fast, cheap, and reliable DNA sequencing could be one of the most disruptive innovations of this decade, as it will pave the way for personalized medicine. In pursuit of such technology, a variety of nanotechnology-based approaches have been explored and established, including sequencing with nanopores. Owing to its unique structure and properties, graphene provides interesting opportunities for the development of a new sequencing technology. In recent years, a wide range of creative ideas for graphene sequencers have been theoretically proposed and the first experimental demonstrations have begun to appear. Here, we review the different approaches to using graphene nanodevices for DNA sequencing, which involve DNA passing through graphene nanopores, nanogaps, and nanoribbons, and the physisorption of DNA on graphene nanostructures. We discuss the advantages and problems of each of these key techniques, and provide a perspective on the use of graphene in future DNA sequencing technology. PMID- 26839261 TI - Fluid leakage near the percolation threshold. AB - Percolation is a concept widely used in many fields of research and refers to the propagation of substances through porous media (e.g., coffee filtering), or the behaviour of complex networks (e.g., spreading of diseases). Percolation theory asserts that most percolative processes are universal, that is, the emergent powerlaws only depend on the general, statistical features of the macroscopic system, but not on specific details of the random realisation. In contrast, our computer simulations of the leakage through a seal--applying common assumptions of elasticity, contact mechanics, and fluid dynamics--show that the critical behaviour (how the flow ceases near the sealing point) solely depends on the microscopic details of the last constriction. It appears fundamentally impossible to accurately predict from statistical properties of the surfaces alone how strongly we have to tighten a water tap to make it stop dripping and also how it starts dripping once we loosen it again. PMID- 26839260 TI - IDO in the Tumor Microenvironment: Inflammation, Counter-Regulation, and Tolerance. AB - Indoleamine 2,3-dioxygenase (IDO) has immunoregulatory roles associated with tryptophan metabolism. These include counter-regulation (controlling inflammation) and acquired tolerance in T cells. Recent findings reveal that IDO can be triggered by innate responses during tumorigenesis, and also by attempted T cell activation, either spontaneous or due to immunotherapy. Here we review the current understanding of mechanisms by which IDO participates in the control of inflammation and in peripheral tolerance. Focusing on the tumor microenvironment, we examine the role of IDO in response to apoptotic cells and the impact of IDO on Treg cell function. We discuss how the counter-regulatory and tolerogenic functions of IDO can be targeted for cancer immunotherapy and present an overview of the current clinical progress in this area. PMID- 26839263 TI - The challenge of instinctive behaviour and Darwin's theory of evolution. AB - In the Origin of Species (1859), Darwin argued that his revolutionary theory of evolution by natural selection represented a significant breakthrough in the understanding of instinctive behaviour. However, many aspects in the development of his thinking on behavioural phenomena indicate that the explanation of this particular organic feature was by no means an easy one, but that it posed an authentic challenge - something that Darwin himself always recognized. This paper explores Darwin's treatment of instincts within his theory of natural selection. Particular attention is given to elucidate how he tackled the difficulties of explaining instincts as evolving mental features. He had to explain and demonstrate its inheritance, variation, and gradual accumulation within populations. The historical and philosophical aspects of his theory are highlighted, as well as his study of the case in which the explanation of instincts represented a 'special difficulty'; that is, the sterile castes of social insects. PMID- 26839262 TI - KLF4 Suppresses Tumor Formation in Genetic and Pharmacological Mouse Models of Colonic Tumorigenesis. AB - The zinc finger transcription factor Kruppel-like factor 4 (KLF4) is frequently downregulated in colorectal cancer. Previous studies showed that KLF4 is a tumor suppressor in the intestinal tract and plays an important role in DNA damage repair mechanisms. Here, the in vivo effects of Klf4 deletion were examined from the mouse intestinal epithelium (Klf4(DeltaIS)) in a genetic or pharmacological setting of colonic tumorigenesis:Apc(Min/+) mutation or carcinogen treatment with azoxymethane (AOM), respectively.Klf4 (DeltaIS)/Apc (Min/+) mice developed significantly more colonic adenomas with 100% penetrance as compared with Apc(Min/+) mice with intact Klf4 (Klf4(fl/fl)/Apc (Min/+)). The colonic epithelium of Klf4 (DeltaIS)/Apc (Min/+)mice showed increased mTOR pathway activity, together with dysregulated epigenetic mechanism as indicated by altered expression of HDAC1 and p300. Colonic adenomas from both genotypes stained positive for gammaH2AX, indicating DNA double-strand breaks. InKlf4 (DeltaIS)/Apc (Min/+) mice, this was associated with reduced nonhomologous end joining (NHEJ) repair and homologous recombination repair (HRR) mechanisms as indicated by reduced Ku70 and Rad51 staining, respectively. In a separate model, following treatment with AOM, Klf4 (DeltaIS) mice developed significantly more colonic tumors than Klf4 (fl/fl) mice, with more Klf4 (DeltaIS) mice harboring K Rasmutations than Klf4 (fl/fl)mice. Compared with AOM-treated Klf4 (fl/fl)mice, adenomas of treated Klf4 (DeltaIS) mice had suppressed NHEJ and HRR mechanisms, as indicated by reduced Ku70 and Rad51 staining. This study highlights the important role of KLF4 in suppressing the development of colonic neoplasia under different tumor-promoting conditions. IMPLICATIONS: The study demonstrates that KLF4 plays a significant role in the pathogenesis of colorectal neoplasia. PMID- 26839265 TI - The minimun island. PMID- 26839264 TI - Altered Carbohydrates Allocation by Associated Bacteria-fungi Interactions in a Bark Beetle-microbe Symbiosis. AB - Insect-microbe interaction is a key area of research in multiplayer symbiosis, yet little is known about the role of microbe-microbe interactions in insect microbe symbioses. The red turpentine beetle (RTB) has destroyed millions of healthy pines in China and forms context-dependent relationships with associated fungi. The adult-associated fungus Leptographium procerum have played key roles in RTB colonization. However, common fungal associates (L. procerum and Ophiostoma minus) with RTB larvae compete for carbohydrates. Here, we report that dominant bacteria associated with RTB larvae buffer the competition by inhibiting the growth and D-glucose consumption of O. minus. However, they didn't inhibit the growth of L. procerum and forced this fungus to consume D-pinitol before consuming D-glucose, even though D-glucose was available and a better carbon source not only for L. procerum but also for RTB larvae and associated bacteria. This suggests the most frequently isolated bacteria associated with RTB larvae could affect fungal growth and the sequence of carbohydrate consumption. Thus, this regulates carbohydrate allocation in the RTB larva-microbe community, which may in turn benefit RTB larvae development. We also discuss the mechanism of carbohydrate allocation in the RTB larva-microbe community, and its potential contribution to the maintenance of a symbiotic community. PMID- 26839266 TI - Ancillary Studies, Including Immunohistochemistry and Molecular Studies, in Pancreatic Cytology. AB - Fine-needle aspiration biopsy of the pancreas is indicated for sampling of solid and cystic masses. Preoperative cytologic diagnosis of pancreatic ductal adenocarcinoma and cystic lesions on cytology can be problematic, and ancillary studies may help confirm diagnosis. Ancillary studies in pancreatic cytology include special stains, immunohistochemistry, mutational analyses of specific genes, cyst fluid analysis of tumor markers and enzymes, and, in some instances, flow cytometry. Proteomics, microRNA sequencing, and whole-exome gene sequencing have been used to illustrate the progression of pancreatic neoplasms and identify key diagnostic markers. This article summarizes recent literature on ancillary studies in pancreatic fine-needle aspiration samples. PMID- 26839267 TI - Ancillary Studies, Including Immunohistochemistry and Molecular Studies, in Lung Cytology. AB - The importance of cytologic techniques for investigation of respiratory conditions has been recognized since the earliest days of clinical cytology. Cytology is able to detect most of mycoses and parasitic and viral infections based on the morphologic recognition of these agents. The most relevant application of lung cytology today is in the diagnosis and management of lung cancer; approximately 70% of those cancers are diagnosed at a late stage and are unresectable. This article addresses the most common ancillary techniques, such as special stains, immunocytochemistry, and molecular testing, used to refine the cytologic diagnosis of lung cancer and to guide personalized therapy. PMID- 26839268 TI - Ancillary Studies in Thyroid Cytopathology. AB - Recent advances in thyroid imaging, clinical evaluation, cytopathology, surgical pathology, and molecular diagnostics have contributed toward greater understanding of thyroid nodules. In particular, the development of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) has brought standardization to the field and the system dovetails well with the implementation of immunohistochemistry and molecular testing to diagnostic practice. Among the molecular strategies available, the application of the molecular panel of common genetic alterations can stratify indeterminate BSRTC diagnoses into low-risk and high-risk groups. The molecular panel markers have a high positive predictive value and therefore, the panel is considered to be a "rule-in" test. In contrast, the Afirma gene expression classifier by Veracyte Corporation is a test that has been reported to have a high negative predictive value, and therefore, considered to be a "rule-out" test. With further advances, refinements are expected to be made. In particular, the application of next-generation sequencing technology holds promise in bringing thyroid cytopathology to the next level. PMID- 26839269 TI - Cytology of the Salivary Glands. AB - Common usage of fine-needle aspirate (FNA) for salivary gland lesions is the preoperative determination of whether a lesion is neoplastic, its lineage, and if neoplastic, whether it is low grade/benign, or high grade. Immunohistochemical stains can be performed on cell blocks to determine lineage and help refine diagnosis, although their performance is not always equivalent to that seen in surgical specimens. Several characteristic translocations have been described in various entities in these categories, and these can be evaluated using fluorescence in situ hybridization. In the future, high-throughput next generation sequencing panels may further refine cytologic diagnosis in salivary tumors. PMID- 26839270 TI - Urine Cytopathology and Ancillary Methods. AB - Urothelial carcinoma (UC) is the most common malignancy of the urinary tract. Cytology and cystoscopy are two of the most commonly used tests for screening and diagnosis of UC. However, the sensitivity of cytology for UC is less than ideal, while cystoscopy is an invasive and expensive procedure. The search for an accurate, sensitive, noninvasive, and cost-effective method for detecting UC has led to the development of ancillary studies using immunological and molecular methods. PMID- 26839271 TI - Ancillary Diagnostics in Gynecologic Cytology. AB - Cytology has been the mainstay of cervical dysplasia and cancer screening in the United States. The specificity of a woman harboring a high-grade lesion when identified as high-grade squamous intraepithelial lesion on Pap test is high; however, the test suffers from low sensitivity. Epidemiology studies have demonstrated that human papillomavirus (HPV) types 16 and 18 account for most cervical squamous cell carcinomas. Tests have been developed to identify high risk HPV, some specifically to identify HPV 16 and 18. Simultaneous to the increase in HPV detection methods, interdisciplinary groups are making recommendations on the managerial use of the tests. PMID- 26839275 TI - Cytology: Moving Forward! PMID- 26839272 TI - Metastatic Tumors of Unknown Origin: Ancillary Testing in Cytologic Specimens. AB - The application of ancillary studies, such as immunostains, to cytopathology has improved the ability to make accurate diagnoses with precise subclassification. Even with these techniques, there are still aspiration and exfoliative cytology cases for which it remains difficult to definitively determine the source and/or subtype. This article focuses on the well-established and novel ancillary studies used in the modern era of cancer diagnoses in cytopathology, particularly in the diagnostic work-up of metastatic tumors without a known primary. PMID- 26839278 TI - NuSAP governs chromosome oscillation by facilitating the Kid-generated polar ejection force. AB - In vertebrate cells, chromosomes oscillate to align precisely during metaphase. NuSAP, a microtubule-associated protein, plays a critical role in stabilizing spindle microtubules. In this study, we utilize 3D time-lapse live-cell imaging to monitor the role of NuSAP in chromosome oscillation and identify NuSAP as a novel regulator of the chromokinesin, Kid. Depletion of NuSAP significantly suppresses the amplitude and velocity of chromosome oscillation. We analyse the effects of NuSAP and Kid depletion in monopolar and bipolar cells with or without kinetochore microtubule depletion. Twelve postulated conditions are deciphered to reveal the contribution of NuSAP to the polar force generated at kinetochore microtubules and to the regulation of the polar ejection force generated by Kid, thus revealing a pivotal role of NuSAP in chromosome oscillation. PMID- 26839279 TI - Three DUF1996 Proteins Localize in Vacuoles and Function in Fungal Responses to Multiple Stresses and Metal Ions. AB - Many annotated fungal genomes harbour high proportions of hypothetical proteins with or without domains of unknown function (DUF). Here, three novel proteins (342-497 amino acids), each containing only a single large DUF1996 (231-250 residues) region with highly conserved head (DPIXXP) and tail (HXDXXXGW) signatures, were expressed as eGFP-tagged fusion proteins and shown to specifically localize in the vacuoles of Beauveria bassiana, a filamentous fungal entomopathogen; therefore, these proteins were named vacuole-localized proteins (VLPs). The VLPs have one to three homologues in other entomopathogenic or non entomopathogenic filamentous fungi but no homologues in yeasts. The large DUF1996 regions can be formulated as D-X4-P-X5-6-H-X-H-X3-G-X25-26-D-X-S-X-YW-X-P-X123 203-CP-X39-48-H-X-D-X3-GW; the identical residues likely involve in a proton antiport system for intracellular homeostasis. Single deletions of three VLP coding genes (vlp1-3) increased fungal sensitivities to cell wall perturbation, high osmolarity, oxidation, and several metal ions. Conidial thermotolerance decreased by ~11% in two Deltavlp mutants, and UV-B resistance decreased by 41 57% in three Deltavlp mutants. All the changes were restored by targeted gene complementation. However, the deletions did not influence fungal growth, conidiation, virulence or Cu(2+) sensitivity. Our findings unveiled a role for the DUF1996 regions of three B. bassiana VLPs in the regulation of multiple stress responses and environmental adaptation. PMID- 26839280 TI - [Adult pneumoccocical sepsis: Should we rule out congenital anesplenia?] PMID- 26839281 TI - Reply. PMID- 26839282 TI - [New President: A new direction and a new goal to reach together]. PMID- 26839283 TI - A Mobile App for Hypertension Management Based on Clinical Practice Guidelines: Development and Deployment. AB - BACKGROUND: Hypertension is a chronic and lifestyle-related disease that requires continuous preventive care. Although there are many evidence-based clinical practice guidelines (CPGs) for hypertension management, applying them to daily management can be difficult for patients with hypertension. A mobile app, based on CPGs, could help patients with hypertension manage their disease. OBJECTIVE: To develop a mobile app for hypertension management based on CPGs and evaluate its effectiveness in patients with hypertension with respect to perceived usefulness, user satisfaction, and medication adherence. METHODS: The hypertension management app (HMA) was developed according to the Web-Roadmap methodology, which includes planning, analysis, design, implementation, and evaluation phases. The HMA was provided to individuals (N=38) with hypertension. Medication adherence was measured before and after using the HMA for 4 weeks. The perceived usefulness and user satisfaction were surveyed in the patients who completed the medication adherence survey. RESULTS: Of the 38 study participants, 29 (76%) participated in medical adherence assessment. Medication adherence, as measured by the Modified Morisky Scale, was significantly improved in these patients after they had used the HMA (P=.001). The perceived usefulness score was 3.7 out of 5. The user satisfaction scores, with respect to using the HMA for blood pressure recording, medication recording, data sending, alerting, recommending, and educating about medication were 4.3, 3.8, 3.1, 3.2, 3.4, and 3.8 out of 5, respectively, in the 19 patients. CONCLUSIONS: This study showed that a mobile app for hypertension management based on CPGs is effective at improving medication adherence. PMID- 26839284 TI - Mode of inheritance for biochemical traits in genetically engineered cotton under water stress. AB - Drought is an abiotic environmental stress that can significantly reduce crop productivity. We examined the mode of inheritance for different biochemical traits including total soluble proteins, chlorophyll a, chlorophyll b, total chlorophyll, carotenoids, total phenolic contents and enzymatic antioxidants (superoxide dismutase, peroxidase and catalase), and their relationship with Bacillus thuringiensis (Bt) toxin under control and drought conditions. Eight genetically diverse cotton genotypes were selfed for two generations to ensure homozygosity. Fifteen F1 hybrids were developed by crossing five non-Bt female lines with three Bt male testers. The F1 hybrids and eight parents were finally evaluated under control (100 % field capacity (FC)) and drought (50 % FC) conditions in 2013. The biochemical traits appeared to be controlled by non additive gene action with low narrow sense heritability estimates. The estimates of general combining ability and specific combining ability for all biochemical traits were significant under control and drought conditions. The genotype-by trait biplot analysis showed the better performance of Bt cotton hybrids when compared with their parental genotypes for various biochemical traits under control and drought conditions. The biplot and path coefficient analyses revealed the prevalence of different relationships between Cry1Ac toxin and biochemical traits in the control and drought conditions. In conclusion, biochemical traits could serve as potential biochemical markers for breeding Bt cotton genotypes without compromising the optimal level of Bt toxin. PMID- 26839285 TI - Effects of flowering phenology and synchrony on the reproductive success of a long-flowering shrub. AB - Flowering phenology and synchrony with biotic and abiotic resources are crucial traits determining the reproductive success in insect-pollinated plants. In seasonal climates, plants flowering for long periods should assure reproductive success when resources are more predictable. In this work, we evaluated the relationship between flowering phenology and synchrony and reproductive success in Hypericum balearicum, a shrub flowering all year round but mainly during spring and summer. We studied two contrasting localities (differing mostly in rainfall) during 3 years, and at different biological scales spanning from localities to individual flowers and fruits. We first monitored (monthly) flowering phenology and reproductive success (fruit and seed set) of plants, and assessed whether in the locality with higher rainfall plants had longer flowering phenology and synchrony and relatively higher reproductive success within or outside the flowering peak. Secondly, we censused pollinators on H. balearicum individuals and measured reproductive success along the flowering peak of each locality to test for an association between (i) richness and abundance of pollinators and (ii) fruit and seed set, and seed weight. We found that most flowers (~90 %) and the highest fruit set (~70 %) were produced during the flowering peak of each locality. Contrary to expectations, plants in the locality with lower rainfall showed more relaxed flowering phenology and synchrony and set more fruits outside the flowering peak. During the flowering peak of each locality, the reproductive success of early-flowering individuals depended on a combination of both pollinator richness and abundance and rainfall; by contrast, reproductive success of late-flowering individuals was most dependent on rainfall. Plant species flowering for long periods in seasonal climates, thus, appear to be ideal organisms to understand how flowering phenology and synchrony match with biotic and abiotic resources, and how this ultimately influences plant reproductive success. PMID- 26839286 TI - A novel nitro-dexamethasone inhibits agr system activity and improves therapeutic effects in MRSA sepsis models without antibiotics. AB - Methicillin-resistant Staphylococcus aureus (MRSA) sepsis is a life-threatening medical condition that involves systemic inflammation throughout the body. Glucocorticoids are widely used in combination with antibiotics in the treatment of MRSA sepsis to fight the overwhelming inflammation. Here, we describe the improved anti-inflammatory properties of a nitric oxide (NO)-releasing derivative of dexamethasone, ND8008. ND8008 affected MRSA biofilm formation, caused biofilm cell death, and reduced the effects of virulence factors, such as alpha-toxin, by inhibiting the activity of the Staphylococcus aureus accessory gene regulator (agr) system. Dosing of mice with ND8008 (127.4 nmol/kg, i.p.) alone greatly reduced the inflammatory response caused by MRSA blood stream infection and considerably increased the survival rate of septic mice. These findings suggest that this novel NO-releasing derivative of dexamethasone ND8008 could be helpful in the treatment of MRSA sepsis. PMID- 26839288 TI - Microleakage in different primary tooth restorations. AB - BACKGROUND: Microleakage may cause tooth sensitivity, secondary caries, discoloration and even failure of the restoration. In order to overcome these potential problems, materials that are able to bind to the tooth structure have been developed, such as composite resin and glass ionomer cement. The purpose of the study was to compare microleakage arising from amalgam (Am), composite resin (CR), glass ionomer (GI), Ketac-Silver (KS), and GI filling with banding (GI+B) when these materials are used for class II restoration of a primary molar. METHODS: Fifty primary molars were collected and class II cavities were prepared on each tooth. The teeth were randomly divided into five groups (Am, CR, GI, KS, and GI+B), each of which received a different material as part of the restoration. The restored teeth then underwent 100 cycles of thermocycling that consisted of 55 degrees C for 30 seconds, 19 degrees C for 20 seconds, and 5 degrees C for 30 seconds. The teeth were then immersed in 0.5% basic fuchsin solution for 24 hours. Afterwards, the teeth were embedded and sectioned mesiodistally through the center of each restoration. Dye penetration associated with the occlusal and cervical margins of each restoration was then assessed. RESULTS: Cervical leakage was greater than occlusal leakage in the CR, GI and KS groups (p < 0.05). When leakage on occlusal margin was examined, however, the Am group showed greater leakage than the CR, GI, and GI+B groups (p < 0.05). When leakage on the cervical margin was examined, the Am group showed greater leakage than the GI and GI+B groups, while the KS group showed greater leakage than the GI+B group (p < 0.05). CONCLUSION: Restorations using GI and GI+B indicated that these materials performed better than the other materials in this study overall. However, none of the materials were entirely devoid of leakage. PMID- 26839289 TI - Benjamin Terry and his rapid razor section method for intraoperative diagnosis. AB - Benjamin Taylor Terry (1876-1955), a little-known pathologist, played a critical role in the popularization of intraoperative diagnostic techniques in the 1920s and 1930s. He developed both a stain and his own rapid razor section method. Intraoperative diagnostic techniques were ultimately responsible for the transition of the practice of pathology and laboratory medicine from private commercial laboratories to a hospital-based practice, forever changing the history of pathology and surgery in North America. Although the intraoperative diagnostic technique he personally developed was reportedly better, faster and more economical than frozen sections, the latter ultimately won the battle for intraoperative diagnostic supremacy. PMID- 26839290 TI - Julian Lewis (1946-2014): A 'serious hero'. AB - Julian Lewis was a gifted medical researcher and writer. His early background was the Classics; then Physics and Math; finally, Molecular Cell Biology. He worked on important questions in early embryonic patterning and the cell communication system, and so cancer research, at King's College London, the Imperial Cancer Research Fund Oxford, and finally, Cancer Research UK London. He was a lifelong coauthor of the international textbook Molecular Biology of the Cell. His final personal battle with cancer was brave and not hidden. Awards included the Waddington Medal, a European Molecular Biology Organization membership, and a Fellowship of the Royal Society. PMID- 26839287 TI - PCH1 integrates circadian and light-signaling pathways to control photoperiod responsive growth in Arabidopsis. AB - Plants react to seasonal change in day length through altering physiology and development. Factors that function to harmonize growth with photoperiod are poorly understood. Here we characterize a new protein that associates with both circadian clock and photoreceptor components, named PHOTOPERIODIC CONTROL OF HYPOCOTYL1 (PCH1). pch1 seedlings have overly elongated hypocotyls specifically under short days while constitutive expression of PCH1 shortens hypocotyls independent of day length. PCH1 peaks at dusk, binds phytochrome B (phyB) in a red light-dependent manner, and co-localizes with phyB into photobodies. PCH1 is necessary and sufficient to promote the biogenesis of large photobodies to maintain an active phyB pool after light exposure, potentiating red-light signaling and prolonging memory of prior illumination. Manipulating PCH1 alters PHYTOCHROME INTERACTING FACTOR 4 levels and regulates light-responsive gene expression. Thus, PCH1 is a new factor that regulates photoperiod-responsive growth by integrating the clock with light perception pathways through modulating daily phyB-signaling. PMID- 26839291 TI - By royal appointment - The Chase Family of Apothecaries. AB - Medical dynasties are not uncommon, but medical dynasties which serve royalty are rare. This paper describes the work and responsibilities of three successive generations of the Chase family who served as apothecaries to a total of seven British monarchs. Two of them were also Masters of the Worshipful Society of Apothecaries of London, as also was a later member of the family. PMID- 26839293 TI - Recent Advances in Follicular Lymphoma: Pediatric, Extranodal, and Follicular Lymphoma in Situ. AB - Follicular lymphoma is a relatively common B-cell lymphoma composed of follicle center B lymphocytes. Follicular lymphomas occurring in the pediatric population and in some extranodal sites exhibit particular clinicopathologic features and clinical behavior that are often distinct from adult nodal follicular lymphoma. A type of "in-situ" follicular lymphoma presents as intrafollicular neoplastic cells in a background of architecturally normal lymphoid tissue and may be difficult to recognize in routine sections. Accurate recognition of the morphologic variants and clinicopathologic subtypes of follicular lymphoma is important to avoid confusing them with other lymphomas and reactive processes; in addition, some of these subtypes of follicular lymphoma display unusually indolent clinical behavior that warrant their separation from "conventional" follicular lymphoma. PMID- 26839294 TI - Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, and Monoclonal B-Cell Lymphocytosis. AB - Chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and monoclonal B-cell lymphocytosis (MBL) are clonal proliferations of small, mature B cells. CLL and SLL are considered neoplastic, although they are indolent and many patients with these lymphomas never require treatment. Most MBL cases share immunophenotypic and genetic features with CLL and SLL but have a small burden of clonal cells. This review focuses on the pathologic features of CLL, SLL, and MBL and their differential diagnoses. Guidelines are provided to separate the entities from one another and to avoid pitfalls in distinguishing these entities from other lymphomas and from reactive lymphoid proliferations. PMID- 26839292 TI - Delineating taxonomic boundaries in the largest species complex of black flies (Simuliidae) in the Oriental Region. AB - Perspicuous assessments of taxonomic boundaries and discovery of cryptic taxa are of paramount importance in interpreting ecological and evolutionary phenomena among black flies (Simuliidae) and combating associated vector-borne diseases. Simulium tani Takaoka & Davies is the largest and perhaps the most taxonomically challenging species complex of black flies in the Oriental Region. We use a DNA sequence-based method to delineate currently recognized chromosomal and morphological taxa in the S. tani complex on the Southeast Asian mainland and Taiwan, while elucidating their phylogenetic relationships. A molecular approach using multiple genes, coupled with morphological and chromosomal data, supported recognition of cytoform K and morphoform 'b' as valid species; indicated that S. xuandei, cytoform L, and morphoform 'a' contain possible cryptic species; and suggested that cytoform B is in the early stages of reproductive isolation whereas lineage sorting is incomplete in cytoforms A, C, and G. PMID- 26839295 TI - Splenic B-Cell Lymphomas/Leukemias. AB - The diagnosis and classification of lymphoproliferative disorders in the spleen are frequently challenging. While some lymphomas, such as hairy cell leukemia and splenic marginal zone lymphoma, characteristically present with primarily splenic involvement, secondary involvement of the spleen may be seen with any lymphoma. Precise classification requires integration of the morphologic findings with clinical data, phenotypic studies, and often cytogenetic and/or molecular genetic analysis. Correlation with the findings in peripheral blood and bone marrow may also be required in some cases. This article discusses the diagnostic approach to splenic-based lymphoproliferative disorders in routine practice and describes the clinicopathologic features of lymphoid neoplasms that characteristically present in the spleen. PMID- 26839296 TI - Diagnosis of Nodal Peripheral T-Cell Lymphomas. AB - Lymph node-based peripheral T-cell lymphomas are rare and exhibit a morphologic spectrum that overlaps with reactive lymphoid hyperplasia, B-cell lymphomas, and Hodgkin lymphoma, presenting a diagnostic challenge. This review focuses on the major categories of lymph node-based peripheral T-cell lymphomas recognized by the 2008 World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. Diagnostic strategies for approaching T-cell neoplasms using a combined clinical, morphologic, immunophenotypic, and genetic approach are presented. Practical information to aid in distinguishing peripheral T-cell lymphomas from other hematologic malignancies and benign conditions is provided. PMID- 26839297 TI - Herpesvirus-Associated B-cell Proliferations. AB - This article reviews the spectrum of Epstein-Barr virus and Kaposi sarcoma herpesvirus (KSHV/HHV-8)-associated B-cell lymphoid proliferations, their pathologic features and clinical presentation, diagnostic criteria, and pathogenetic aspects. Emphasis is on the differential diagnosis issues and difficulties that the pathologist may face for the correct identification and interpretation of these lesions. PMID- 26839298 TI - Diagnosis of Burkitt Lymphoma and Related High-Grade B-Cell Neoplasms. AB - Burkitt lymphoma (BL) is an aggressive B-cell neoplasm with an extremely short doubling time that mainly affects children and young adults. Despite having several characteristic features, none is entirely specific for BL and the differential diagnosis may include diffuse large B-cell lymphoma (DLBCL), B lymphoblastic leukemia/lymphoma, and B-cell lymphoma unclassifiable with features intermediate between DLBCL and BL. We outline a practical approach to establish a diagnosis of BL and distinguish it from other high-grade B-cell malignancies. We pay particular attention to B-cell lymphomas with features intermediate between DLBCL and BL, a new diagnostic category in the 2008 World Health Organization classification system that provides a framework for categorizing challenging cases not meeting diagnostic criteria for either "classic" BL or DLBCL. PMID- 26839299 TI - Update on the Diagnosis and Classification of the Plasma Cell Neoplasms. AB - The plasma cell neoplasms are malignancies of the most terminally differentiated cells in B-cell ontogeny and are usually associated with the production of a monoclonal immunoglobulin molecule or M protein. These malignancies include tumors whose clinical manifestations are directly attributable to the end-organ damage induced by the dysregulated proliferation of neoplastic plasma cells. In contrast, disorders, such as primary amyloidosis, have a paradoxically low burden of neoplastic plasma cells, rendered highly pathogenic by the end-organ damage induced by deposition of the secreted paraprotein. In this article, discussion focuses on plasma cell myeloma. The molecular pathogenesis of plasma cell myeloma is reviewed and the diagnosis of the plasma cell neoplasms discussed. PMID- 26839300 TI - Pediatric Bone Marrow Interpretation. AB - The evaluation of pediatric bone marrow poses specific challenges when compared with the general adult population. These challenges stem in part from the higher likelihood of congenital disorders with hematopoietic manifestations, some of which may give rise to hematologic malignancies. Familiarity with the spectrum of disorders seen in the pediatric age group allows for an appropriate and focused differential diagnosis. This review addresses the diagnostic workup of pediatric bone marrow samples, as directed by the peripheral blood and bone marrow findings in the context of the patient's clinical history. Recommendations for the appropriate use of ancillary studies in various scenarios are provided. PMID- 26839301 TI - Diagnosis of Myelodysplastic Syndromes in Cytopenic Patients. AB - Sustained clinical cytopenia is a frequent laboratory finding in ambulatory and hospitalized patients. For pathologists and hematopathologists who examine the bone marrow (BM), a diagnosis of cytopenia secondary to an infiltrative BM process or acute leukemia can be readily established based on morphologic evaluation and flow cytometry immunophenotyping. However, it can be more challenging to establish a diagnosis of myelodysplastic syndrome (MDS). In this article, the practical approaches for establishing or excluding a diagnosis of MDS (especially low-grade MDS) in patients with clinical cytopenia are discussed along with the current diagnostic recommendations provided by the World Health Organization and the International Working Group for MDS. PMID- 26839302 TI - Acute Myeloid Leukemia With Myelodysplasia-Related Changes: A New Definition. AB - Acute myeloid leukemia (AML) with multilineage dysplasia was introduced in the 2001 World Health Organization (WHO) classification to encompass cases of AML characterized by myelodysplastic syndrome-like features. The 2008 WHO classification revised this group into a new category, AML with myelodysplasia related changes (AML-MRC). The category now includes patients with at least 20% blasts in peripheral blood or bone marrow and any of the following: (1) AML arising from a previous MDS or mixed MDS/myeloproliferative neoplasm, (2) AML with a specific MDS-associated cytogenetic abnormality and/or (3) AML with multilineage dysplasia. Up to 48% of all patients with AML are encompassed within the AML-MRC subgroup. AML-MRC patients have worse prognosis compared with patients with AML, not otherwise specified. PMID- 26839303 TI - Histiocytic and Dendritic Cell Neoplasms. AB - This article reviews the features of dendritic cells (DCs) of myeloid-derived, plasmacytoid, and follicle-associated types and tumors of these cells, as well as myeloid sarcoma. The morphologic and immunophenotypic features in this group of neoplasms is featured, including mature neoplasms such as Langerhans cell histiocytosis, its malignant counterpart Langerhans cell sarcoma, and S100 negative histiocytic proliferations. More immature or precursor malignancies in this group include myeloid and monocytic leukemias presenting in extramedullary tissues as well as the newly codified blastic plasmacytoid dendritic cell neoplasm. Although likely not related histogenetically to myeloid-derived DCs, mesenchymal-type lymph node tumors including follicular dendritic cell and fibroblastic reticulum sarcomas are also discussed. All of these neoplasms can exhibit a range of immunophenotypic and morphologic features that underscore the plasticity of the non-neoplastic precursors from which they are derived. PMID- 26839304 TI - Systemic Mastocytosis. AB - An unusual disease, mastocytosis challenges the pathologist with a variety of morphologic appearances and heterogeneous clinical presentations ranging from skin manifestations (pruritus, urticaria, dermatographism) to systemic signs and symptoms indicative of mast cell mediator release, including flushing, hypotension, headache, and anaphylaxis among others. In this article, we focus on recognizing the cytology, histopathology, clinical features, and prognostic implications of systemic mastocytosis, a clonal and neoplastic mast cell proliferation infiltrating extracutaneous organ(s) with or without skin involvement. Diagnostic pitfalls are reviewed with ancillary studies to help unmask the mast cell and exclude morphologic mimics. PMID- 26839305 TI - Preface: Diagnostic Hematopathology: Aiming at a Moving Target. PMID- 26839306 TI - Antagonizing the Hedgehog Pathway with Vismodegib Impairs Malignant Pleural Mesothelioma Growth In Vivo by Affecting Stroma. AB - An autocrine-driven upregulation of the Hedgehog (Hh) signaling pathway has been described in malignant pleural mesothelioma (MPM), in which the ligand, desert Hh (DHH), was produced from tumor cells. However, our investigation revealed that the Hh pathway is activated in both tumor and stroma of MPM tumor specimens and an orthotopic immunocompetent rat MPM model. This was demonstrated by positive immunohistochemical staining of Glioma-associated oncogene 1 (GLI1) and Patched1 (PTCH1) in both tumor and stromal fractions. DHH was predominantly expressed in the tumor fractions. To further investigate the role of the Hh pathway in MPM stroma, we antagonized Hh signaling in the rat model of MPM using a Hh antagonist, vismodegib, (100 mg/kg orally). Daily treatment with vismodegib efficiently downregulated Hh target genes Gli1, Hedgehog Interacting Protein (Hhip), and Ptch1, and caused a significant reduction of tumor volume and tumor growth delay. Immunohistochemical analyses revealed that vismodegib treatment primarily downregulated GLI1 and HHIP in the stromal compartment along with a reduced expression of previously described fibroblast Hh-responsive genes such as Fibronectin (Fn1) and Vegfa Primary cells isolated from the rat model cultured in 3% O2 continued to express Dhh but did not respond to vismodegib in vitro However, culture supernatant from these cells stimulated Gli1, Ptch1, and Fn1 expression in mouse embryonic fibroblasts, which was suppressed by vismodegib. Our study provides new evidence regarding the role of Hh signaling in MPM stroma in the maintenance of tumor growth, emphasizing Hh signaling as a treatment target for MPM. Mol Cancer Ther; 15(5); 1095-105. (c)2016 AACR. PMID- 26839307 TI - Intermittent High-Dose Scheduling of AZD8835, a Novel Selective Inhibitor of PI3Kalpha and PI3Kdelta, Demonstrates Treatment Strategies for PIK3CA-Dependent Breast Cancers. AB - The PIK3CA gene, encoding the p110alpha catalytic unit of PI3Kalpha, is one of the most frequently mutated oncogenes in human cancer. Hence, PI3Kalpha is a target subject to intensive efforts in identifying inhibitors and evaluating their therapeutic potential. Here, we report studies with a novel PI3K inhibitor, AZD8835, currently in phase I clinical evaluation. AZD8835 is a potent inhibitor of PI3Kalpha and PI3Kdelta with selectivity versus PI3Kbeta, PI3Kgamma, and other kinases that preferentially inhibited growth in cells with mutant PIK3CA status, such as in estrogen receptor-positive (ER(+)) breast cancer cell lines BT474, MCF7, and T47D (sub-MUmol/L GI50s). Consistent with this, AZD8835 demonstrated antitumor efficacy in corresponding breast cancer xenograft models when dosed continuously. In addition, an alternative approach of intermittent high-dose scheduling (IHDS) was explored given our observations that higher exposures achieved greater pathway inhibition and induced apoptosis. Indeed, using IHDS, monotherapy AZD8835 was able to induce tumor xenograft regression. Furthermore, AZD8835 IHDS in combination with other targeted therapeutic agents further enhanced antitumor activity (up to 92% regression). Combination partners were prioritized on the basis of our mechanistic insights demonstrating signaling pathway cross-talk, with a focus on targeting interdependent ER and/or CDK4/6 pathways or alternatively a node (mTOR) in the PI3K-pathway, approaches with demonstrated clinical benefit in ER(+) breast cancer patients. In summary, AZD8835 IHDS delivers strong antitumor efficacy in a range of combination settings and provides a promising alternative to continuous dosing to optimize the therapeutic index in patients. Such schedules merit clinical evaluation. Mol Cancer Ther; 15(5); 877-89. (c)2016 AACR. PMID- 26839309 TI - The Complex Role of Neutrophils in Tumor Angiogenesis and Metastasis. AB - Chronic inflammation fosters cancer development and progression and also modulates tumor responses to anticancer therapies. Neutrophils are key effector cells in innate immunity and are known to play a critical role in various inflammatory disorders. However, the functions of neutrophils in cancer pathogenesis have been largely neglected until recently and still remain poorly characterized compared with other immune cells in the tumor microenvironment. We highlight recent findings on the mechanisms by which tumor cells, in cooperation with tumor-associated stromal cells, induce expansion, recruitment, and polarization of neutrophils. We also review the multifaceted roles that neutrophils play in different aspects of cancer development and progression, with an emphasis on tumor angiogenesis and metastasis. PMID- 26839308 TI - Combined Effects of Suberoylanilide Hydroxamic Acid and Cisplatin on Radiation Sensitivity and Cancer Cell Invasion in Non-Small Cell Lung Cancer. AB - Lung cancer is a leading cause of cancer-related mortality worldwide, and concurrent chemoradiotherapy has been explored as a therapeutic option. However, the chemotherapeutic agents cannot be administered for most patients at full doses safely with radical doses of thoracic radiation, and further optimizations of the chemotherapy regimen to be given with radiation are needed. In this study, we examined the effects of suberoylanilide hydroxamic acid (SAHA) and cisplatin on DNA damage repairs, and determined the combination effects of SAHA and cisplatin on human non-small cell lung cancer (NSCLC) cells in response to treatment of ionizing radiation (IR), and on tumor growth of lung cancer H460 xenografts receiving radiotherapy. We also investigated the potential differentiation effect of SAHA and its consequences on cancer cell invasion. Our results showed that SAHA and cisplatin compromise distinct DNA damage repair pathways, and treatment with SAHA enhanced synergistic radiosensitization effects of cisplatin in established NSCLC cell lines in a p53-independent manner, and decreased the DNA damage repair capability in cisplatin-treated primary NSCLC tumor tissues in response to IR. SAHA combined with cisplatin also significantly increased inhibitory effect of radiotherapy on tumor growth in the mouse xenograft model. In addition, SAHA can induce differentiation in stem cell-like cancer cell population, reduce tumorigenicity, and decrease invasiveness of human lung cancer cells. In conclusion, our data suggest a potential clinical impact for SAHA as a radiosensitizer and as a part of a chemoradiotherapy regimen for NSCLC. Mol Cancer Ther; 15(5); 842-53. (c)2016 AACR. PMID- 26839310 TI - Correction: Human Leukocyte Antigen (HLA) A*1101-Restricted Epstein-Barr Virus Specific T-cell Receptor Gene Transfer to Target Nasopharyngeal Carcinoma. PMID- 26839311 TI - Protease-activated Receptor-2 (PAR-2)-mediated Nf-kappaB Activation Suppresses Inflammation-associated Tumor Suppressor MicroRNAs in Oral Squamous Cell Carcinoma. AB - Oral cancer is the sixth most common cause of death from cancer with an estimated 400,000 deaths worldwide and a low (50%) 5-year survival rate. The most common form of oral cancer is oral squamous cell carcinoma (OSCC). OSCC is highly inflammatory and invasive, and the degree of inflammation correlates with tumor aggressiveness. The G protein-coupled receptor protease-activated receptor-2 (PAR 2) plays a key role in inflammation. PAR-2 is activated via proteolytic cleavage by trypsin-like serine proteases, including kallikrein-5 (KLK5), or by treatment with activating peptides. PAR-2 activation induces G protein-alpha-mediated signaling, mobilizing intracellular calcium and Nf-kappaB signaling, leading to the increased expression of pro-inflammatory mRNAs. Little is known, however, about PAR-2 regulation of inflammation-related microRNAs. Here, we assess PAR-2 expression and function in OSCC cell lines and tissues. Stimulation of PAR-2 activates Nf-kappaB signaling, resulting in RelA nuclear translocation and enhanced expression of pro-inflammatory mRNAs. Concomitantly, suppression of the anti-inflammatory tumor suppressor microRNAs let-7d, miR-23b, and miR-200c was observed following PAR-2 stimulation. Analysis of orthotopic oral tumors generated by cells with reduced KLK5 expression showed smaller, less aggressive lesions with reduced inflammatory infiltrate relative to tumors generated by KLK5 expressing control cells. Together, these data support a model wherein KLK5 mediated PAR-2 activation regulates the expression of inflammation-associated mRNAs and microRNAs, thereby modulating progression of oral tumors. PMID- 26839312 TI - The Transmembrane Domain Mediates Tetramerization of alpha-Amino-3-hydroxy-5 methyl-4-isoxazolepropionic Acid (AMPA) Receptors. AB - AMPA receptors (AMPARs) mediate fast excitatory neurotransmission in the central nervous system. Functional AMPARs are tetrameric complexes with a highly modular structure, consisting of four evolutionarily distinct structural domains: an amino-terminal domain (ATD), a ligand-binding domain (LBD), a channel-forming transmembrane domain (TMD), and a carboxyl-terminal domain (CTD). Here we show that the isolated TMD of the GluA1 AMPAR is fully capable of tetramerization. Additionally, removal of the extracellular domains from the receptor did not affect membrane topology or surface delivery. Furthermore, whereas the ATD and CTD contribute positively to tetramerization, the LBD presents a barrier to the process by reducing the stability of the receptor complex. These experiments pinpoint the TMD as the "tetramerization domain" for AMPARs, with other domains playing modulatory roles. They also raise intriguing questions about the evolution of iGluRs as well as the mechanisms regulating the biogenesis of AMPAR complexes. PMID- 26839313 TI - Mitigation of NADPH Oxidase 2 Activity as a Strategy to Inhibit Peroxynitrite Formation. AB - Using high throughput screening-compatible assays for superoxide and hydrogen peroxide, we identified potential inhibitors of the NADPH oxidase (Nox2) isoform from a small library of bioactive compounds. By using multiple probes (hydroethidine, hydropropidine, Amplex Red, and coumarin boronate) with well defined redox chemistry that form highly diagnostic marker products upon reaction with superoxide (O2 ()), hydrogen peroxide (H2O2), and peroxynitrite (ONOO(-)), the number of false positives was greatly decreased. Selected hits for Nox2 were further screened for their ability to inhibit ONOO(-)formation in activated macrophages. A new diagnostic marker product for ONOO(-)is reported. We conclude that the newly developed high throughput screening/reactive oxygen species assays could also be used to identify potential inhibitors of ONOO(-)formed from Nox2 derived O2 ()and nitric oxide synthase-derived nitric oxide. PMID- 26839316 TI - Ensuring safe anaesthesia for neonates, infants and young children: what really matters. PMID- 26839314 TI - Ubiquitin-specific Protease 20 Regulates the Reciprocal Functions of beta Arrestin2 in Toll-like Receptor 4-promoted Nuclear Factor kappaB (NFkappaB) Activation. AB - Toll-like receptor 4 (TLR4) promotes vascular inflammatory disorders such as neointimal hyperplasia and atherosclerosis. TLR4 triggers NFkappaB signaling through the ubiquitin ligase TRAF6 (tumor necrosis factor receptor-associated factor 6). TRAF6 activity can be impeded by deubiquitinating enzymes like ubiquitin-specific protease 20 (USP20), which can reverse TRAF6 autoubiquitination, and by association with the multifunctional adaptor protein beta-arrestin2. Although beta-arrestin2 effects on TRAF6 suggest an anti inflammatory role, physiologic beta-arrestin2 promotes inflammation in atherosclerosis and neointimal hyperplasia. We hypothesized that anti- and proinflammatory dimensions of beta-arrestin2 activity could be dictated by beta arrestin2's ubiquitination status, which has been linked with its ability to scaffold and localize activated ERK1/2 to signalosomes. With purified proteins and in intact cells, our protein interaction studies showed that TRAF6/USP20 association and subsequent USP20-mediated TRAF6 deubiquitination were beta arrestin2-dependent. Generation of transgenic mice with smooth muscle cell specific expression of either USP20 or its catalytically inactive mutant revealed anti-inflammatory effects of USP20in vivoandin vitro Carotid endothelial denudation showed that antagonizing smooth muscle cell USP20 activity increased NFkappaB activation and neointimal hyperplasia. We found that beta-arrestin2 ubiquitination was promoted by TLR4 and reversed by USP20. The association of USP20 with beta-arrestin2 was augmented when beta-arrestin2 ubiquitination was prevented and reduced when beta-arrestin2 ubiquitination was rendered constitutive. Constitutive beta-arrestin2 ubiquitination also augmented NFkappaB activation. We infer that pro- and anti-inflammatory activities of beta-arrestin2 are determined by beta-arrestin2 ubiquitination and that changes in USP20 expression and/or activity can therefore regulate inflammatory responses, at least in part, by defining the ubiquitination status of beta-arrestin2. PMID- 26839315 TI - Angiopoietin-like Protein 2 Is a Multistep Regulator of Inflammatory Neovascularization in a Murine Model of Age-related Macular Degeneration. AB - Choroidal neovascularization (CNV) is a pathogenic process of age-related macular degeneration, a vision-threatening disease. The retinal pigment epithelium and macrophages both influence CNV development. However, the underlying mechanisms remain obscure. Here, we focus on Angptl2 (angiopoietin-like protein 2), a cytokine involved in age-related systemic diseases. Angptl2 was originally identified as an adipocytokine and is also expressed in the eye. Using a laser induced CNV model, we found thatAngptl2KO mice exhibited suppressed CNV development with reduced macrophage recruitment and inflammatory mediator induction. The mediators monocyte chemotactic protein-1, interleukin-1beta (Il 1beta),Il-6, matrix metalloprotease-9 (Mmp-9), and transforming growth factor beta1 (Tgf-beta1) that were up-regulated during CNV development were all suppressed in the retinal pigment epithelium-choroid of CNV models generated in theAngptl2KO mice. Bone marrow transplantation using wild-type and KO mice suggested that both bone marrow-derived and host-derived Angptl2 were responsible for macrophage recruitment and CNV development. Peritoneal macrophages derived fromAngptl2KO mice expressed lower levels of the inflammatory mediators. In the wild-type peritoneal macrophages and RAW264.7 cells, Angptl2 induced the mediators via integrins alpha4 and beta2, followed by the downstream activation of NF-kappaB and ERK. The activation of NF-kappaB and ERK by Angptl2 also promoted macrophage migration. Therefore, Angptl2 from focal tissue might trigger macrophage recruitment, and that from recruited macrophages might promote expression of inflammatory mediators including Angptl2 in an autocrine and/or paracrine fashion to facilitate CNV development. Angptl2 might therefore represent a multistep regulator of CNV pathogenesis and serve as a new therapeutic target for age-related macular degeneration. PMID- 26839317 TI - Adaptation of Habrobracon hebetor (Hymenoptera: Braconidae) to Rearing on Ephestia kuehniella (Lepidoptera: Pyralidae) and Helicoverpa armigera (Lepidoptera: Noctuidae). AB - Food characteristics strongly regulate digestive enzymatic activity of insects through direct influences on their midgut mechanisms. Insect performance is better on diets that contain nutrients in proportions that fit its digestive enzymes. Little is known about the influences of rearing history on parasitism success of Habrobracon hebetor Say. This research focused on the effect of nutrient regulation on survival, development, and parasitism of H. hebetor. Life history and digestive enzyme activity of fourth-stage larvae of H. hebetor were studied when reared on Ephestia kuehniella Zeller. This parasitoid was then introduced to Helicoverpa armigera (Hubner), and above-mentioned parameters were also studied in the first and fourth generations after transfer. In term of parasitism success, H. hebetor preferred E. kuehniella over He. armigera. When the first and fourth generations of He. armigera-reared H. hebetor were compared, the rearing history affected the life history and enzymatic activity of the parasitoid. A better performance of H. hebetor was achieved after it was reared on He. armigera for the four generations. Because, digestive alpha-amylase and general protease of the parasitoid were matched with the new host, it used reserve energy for a better performance. Thus, a better performance of H. hebetor could be obtained when the parasitoid was reared on its original host for at least four generations. PMID- 26839318 TI - Geographic Variation of Diapause and Sensitive Stages of Photoperiodic Response in Laodelphax striatellus Fallen (Hemiptera: Delphacidae). AB - Large numbers of the small brown planthopper Laodelphax striatellus (Fallen) (Hemiptera: Delphacidae) occur in temperate regions, causing severe losses in rice, wheat, and other economically important crops. The planthoppers enter diapause in the third- or fourth-instar nymph stage, induced by short photoperiods and low temperatures. To investigate the geographic variation in L. striatellus diapause, we compared the incidence of nymphal diapause under various constant temperature (20 and 27 degrees C) and a photoperiod of 4:20, 8:16, 10:14, 12:12, 14:10, and 16:8 (L:D) h regimes among three populations collected from Hanoi (21.02 degrees N, 105.85 degrees E, northern Vietnam), Jiangyan (32.51 degrees N, 120.15 degrees E, eastern China), and Changchun (43.89 degrees N, 125.32 degrees E, north-eastern China). Our results indicated that there were significant geographic variations in the diapause of L. striatellus. When the original latitude of the populations increased, higher diapause incidence and longer critical photoperiod (CP) were exhibited. The CPs of the Jiangyan and Changchun populations were ~ 12 hr 30 min and 13 hr at 20 degrees C, and 11 hr and 11 hr 20 min at 27 degrees C, respectively. The second- and third-instar nymphs were at the stage most sensitive to the photoperiod. However, when the fourth- and fifth-instar nymphs were transferred to a long photoperiod, the diapause-inducing effect of the short photoperiod on young instars was almost reversed. The considerable geographic variations in the nymphal diapause of L. striatellus reflect their adaptation in response to a variable environment and provide insights to develop effective pest management strategies. PMID- 26839320 TI - Computational recognition for long non-coding RNA (lncRNA): Software and databases. AB - Since the completion of the Human Genome Project, it has been widely established that most DNA is not transcribed into proteins. These non-protein-coding regions are believed to be moderators within transcriptional and post-transcriptional processes, which play key roles in the onset of diseases. Long non-coding RNAs (lncRNAs) are generally lacking in conserved motifs typically used for detection and thus hard to identify, but nonetheless present certain characteristic features that can be exploited by bioinformatics methods. By combining lncRNA detection with known miRNA, RNA-binding protein and chromatin interaction, current tools are able to recognize and functionally annotate large number of lncRNAs. This review discusses databases and platforms dedicated to cataloging and annotating lncRNAs, as well as tools geared at discovering novel sequences. We emphasize the issues posed by the diversity of lncRNAs and their complex interaction mechanisms, as well as technical issues such as lack of unified nomenclature. We hope that this wide overview of existing platforms and databases might help guide biologists toward the tools they need to analyze their experimental data, while our discussion of limitations and of current lncRNA related methods may assist in the development of new computational tools. PMID- 26839319 TI - Phospho-ubiquitin: upending the PINK-Parkin-ubiquitin cascade. AB - Mitochondria with decreased membrane potential are characterized by defects in protein import into the matrix and impairments in high-efficiency synthesis of ATP. These low-quality mitochondria are marked with ubiquitin for selective degradation. Key factors in this mechanism are PTEN-induced putative kinase 1 (PINK1, a mitochondrial kinase) and Parkin (a ubiquitin ligase), disruption of which has been implicated in predisposition to Parkinson's disease. Previously, the clearance of damaged mitochondria had been thought to be the end result of a simple cascading reaction of PINK1-Parkin-ubiquitin. However, in the past year, several research groups including ours unexpectedly revealed that Parkin regulation is mediated by PINK1-dependent phosphorylation of ubiquitin. These results overturned the simple hierarchy that posited PINK1 and ubiquitin as the upstream and downstream factors of Parkin, respectively. Although ubiquitylation is well-known as a post-translational modification, it has recently become clear that ubiquitin itself can be modified, and that this modification unexpectedly converts ubiquitin to a factor that functions in retrograde signalling. PMID- 26839321 TI - Betahistine decreases olanzapine-induced weight gain and somnolence in humans. AB - Olanzapine's efficacy in schizophrenia is attributed to antagonism of dopamine and serotonin receptors. Olanzapine is also a potent histamine-H1 antagonist that results in weight gain and somnolence. Betahistine is a centrally acting histamine-H1 agonist, and therefore may reduce olanzapine's effect on histamine receptors in the brain. Olanzapine's high affinity for the histamine-H1 receptor warrants the use of high doses of betahistine. Forty-eight healthy women were recruited and randomized to receive either betahistine 144 mg/day or matching placebo for 4 weeks. Due to the high dose of betahistine, olanzapine was started only on the second week and titrated up to 10 mg/day, and co-administration continued for an additional 2 weeks. Only nominal differences in adverse events were noted between the treatment groups. Betahistine caused a 37% reduction in mean weight gain (1.24 kg in the betahistine arm vs. 1.93 kg in the placebo arm; p=.049) and 60% reduction in the mean increase in daytime Epworth sleepiness scores (1.82 units in the betahistine group vs. 3.57 units in the placebo group; p=.042). The present study suggests that betahistine-olanzapine co administration, in healthy female subjects, yields an acceptable safety profile with mitigation of weight gain and somnolence. This should be further tested in a patient cohort. PMID- 26839322 TI - Cannabis craving in response to laboratory-induced social stress among racially diverse cannabis users: The impact of social anxiety disorder. AB - Social anxiety disorder appears to be a risk factor for cannabis-related problems. Although it is presumed that increases in cannabis craving during elevated social anxiety reflect an intent to cope with greater negative affectivity, it is unclear whether increases in physiological arousal during social stress are related to cannabis craving, especially among those with social anxiety disorder. Similarly, no studies have assessed motivational reasons for cannabis use during elevated social stress. Thus, the current study tested whether increases in state social anxiety (measured subjectively and via physiological arousal) were related to greater cannabis craving among 126 current cannabis users (88.9% with cannabis use disorder, 31.7% with social anxiety disorder, 54.0% non-Hispanic Caucasian) randomly assigned to either a social interaction or reading task. As predicted, cannabis users in the social interaction condition reported greater cannabis craving than those in the reading condition. This effect was particularly evident among those with social anxiety disorder. Although physiological arousal did not moderate the relationship between condition and craving, coping motives were the most common reasons cited for wanting to use cannabis and were reported more among those in the social interaction task. These experimental results uniquely add to a growing literature suggesting the importance of elevated state social anxiety (especially among those with social anxiety disorder) in cannabis use vulnerability processes. PMID- 26839323 TI - Plasma ghrelin levels as a predictor of adverse renal events due to cisplatin based chemotherapy in patients with esophageal cancer. AB - OBJECTIVE: Although combination chemotherapy with docetaxel, cisplatin and 5 fluorouracil demonstrates high response rates in esophageal squamous cell carcinoma, patients treated with docetaxel, cisplatin and 5-fluorouracil frequently experience acute kidney injury. Ghrelin has shown renal protective effects in an experimental acute kidney injury model by reducing tubular apoptosis. In this prospective observational study, we evaluated the association between plasma ghrelin concentrations and docetaxel, cisplatin and 5-fluorouracil related acute kidney injury. METHODS: Forty consecutive patients with esophageal squamous cell carcinoma who received docetaxel, cisplatin and 5-fluorouracil from October 2013 to July 2014 were enrolled in this study. Serum creatinine and urinary alpha-1 microglobulin, a marker of renal tubular damage, were measured six times during chemotherapy. RESULTS: The increases of creatinine level which is defined in Common Terminology Criteria for Adverse Event were observed less frequently in patients with acyl ghrelin concentrations of >=9.6 fmol/ml (HAG group) than in those with concentrations <9.6 fmol/ml on Day 2 (LAG group) (P= 0.024). Serum creatinine was significantly lower in the HAG group than in the LAG group (Day 8: 0.79 +/- 0.16 vs. 0.97 +/- 0.26, P = 0.024; Day 11: 0.85 +/- 0.19 vs. 1.08 +/- 0.34 mg/dl, P = 0.049). Urinary alpha-1 microglobulin levels were significantly lower in the HAG group than in the LAG group (Day 4: 2.48 +/- 1.83 vs. 3.33 +/- 1.41, P = 0.011; Day 8: 4.67 +/- 5.50 vs. 5.09 +/- 2.54, P = 0.011; Day 11: 11.55 +/- 13.78 vs. 16.43 +/- 17.84 mg/l, P = 0.020). CONCLUSIONS: Plasma acyl ghrelin concentrations on Day 2 of chemotherapy may be a potential predictor of docetaxel, cisplatin and 5-fluorouracil-induced acute kidney injury. PMID- 26839324 TI - Miniature Swine for Preclinical Modeling of Complexities of Human Disease for Translational Scientific Discovery and Accelerated Development of Therapies and Medical Devices. AB - Noncommunicable diseases, including cardiovascular disease, diabetes, chronic respiratory disease, and cancer, are the leading cause of death in the world. The cost, both monetary and time, of developing therapies to prevent, treat, or manage these diseases has become unsustainable. A contributing factor is inefficient and ineffective preclinical research, in which the animal models utilized do not replicate the complex physiology that influences disease. An ideal preclinical animal model is one that responds similarly to intrinsic and extrinsic influences, providing high translatability and concordance of preclinical findings to humans. The overwhelming genetic, anatomical, physiological, and pathophysiological similarities to humans make miniature swine an ideal model for preclinical studies of human disease. Additionally, recent development of precision gene-editing tools for creation of novel genetic swine models allows the modeling of highly complex pathophysiology and comorbidities. As such, the utilization of swine models in early research allows for the evaluation of novel drug and technology efficacy while encouraging redesign and refinement before committing to clinical testing. This review highlights the appropriateness of the miniature swine for modeling complex physiologic systems, presenting it as a highly translational preclinical platform to validate efficacy and safety of therapies and devices. PMID- 26839325 TI - Quantification of Hepcidin-related Iron Accumulation in the Rat Liver. AB - Hepcidin was originally detected as a liver peptide with antimicrobial activity and it functions as a central regulator in the systemic iron metabolism. Consequently suppression of hepcidin leads to iron accumulation in the liver. AbbVie developed a monoclonal antibody ([mAb]; repulsive guidance molecule [RGMa/c] mAb) that downregulates hepcidin expression by influencing the RGMc/bone morphogenetic protein (BMP)/neogenin receptor complex and causes iron deposition in the liver. In a dose range finding study with RGMa/c mAb, rats were treated with different dose levels for a total of 4 weekly doses. The results of this morphometric analysis in the liver showed that iron accumulation is not homogenous between liver lobes and the left lateral lobe was the most responsive lobe in the rat. Quantitative hepcidin messenger RNA analysis showed that the left lateral lobe was the most responsive lobe showing hepcidin downregulation with increasing antibody dose. In addition, the morphometric analysis had higher sensitivity than the chemical iron extraction and quantification using a colorimetric assay. In conclusion, the Prussian blue stain in combination with semi-quantitative and quantitative morphometric analysis is the most reliable method to demonstrate iron accumulation in the liver compared to direct measurement of iron in unfixed tissue using a colorimetric assay. PMID- 26839327 TI - Minipigs in Translational Immunosafety Sciences: A Perspective. AB - The porcine immune system has been studied especially with regard to infectious diseases of the domestic pig, highlighting the economic importance of the pig in agriculture. Recently, in particular, minipigs have received attention as alternative species to dogs or nonhuman primates in drug safety evaluations. The increasing number of new drug targets investigated to modulate immunological pathways has triggered renewed interest to further explore the porcine immune system. Comparative immunological studies of minipigs with other species broaden the translational models investigated in drug safety evaluations. The porcine immune system overall seems functionally similar to other mammalian species, but there are some anatomical, immunophenotypical, and functional differences. Here, we briefly review current knowledge of the innate and adaptive immune system in pigs and minipigs. In conclusion, more systematic and cross-species comparisons are needed to assess the significance of immunological findings in minipigs in the context of translational safety sciences. PMID- 26839328 TI - Dermatotoxicology: Safety Evaluation of Topical Products in Minipigs: Study Designs and Practical Considerations. AB - The minipig has long been identified as the nonrodent animal of choice for preclinical safety evaluation of topically applied materials. This article reviews types of topical applications, study designs, and practical considerations. Dermal administration to the minipig presents multiple challenges. Issues to be considered are the area of exposure, the nature of the test article, the need for covering of the dose site, preparation of the dose site, and procedures for administration. The potential for cross-contamination (exposure of control animals to test article) is very high in topical studies and appropriate safeguards to prevent this are discussed. Topical administration to the intact skin is the most commonly utilized form of safety evaluation, but procedures have also been developed for intradermal administration and for the use of nonintact/wounded skin; these will be discussed. Evaluation of local (topical) effects is critical and can become complicated. Considerations in evaluations of the skin are interobserver variability, use of different scoring systems and discrepancies betweenin vivoobservations, necropsy observations, and microscopic pathology findings. Causes for apparent discrepancies and suggestions for practical resolution through appropriate procedures are discussed. Practical issues in necropsy and histotechnology procedures and techniques to optimize preservation of skin are also discussed. PMID- 26839326 TI - Computed Tomography and Magnetic Resonance Imaging for Longitudinal Characterization of Lung Structure Changes in a Yucatan Miniature Pig Silicosis Model. AB - Medical imaging is a rapidly advancing field enabling the repeated, noninvasive assessment of physiological structure and function. These beneficial characteristics can supplement studies in swine by mirroring the clinical functions of detection, diagnosis, and monitoring in humans. In addition, swine may serve as a human surrogate, facilitating the development and comparison of new imaging protocols for translation to humans. This study presents methods for pulmonary imaging developed for monitoring pulmonary disease initiation and progression in a pig exposure model with computed tomography and magnetic resonance imaging. In particular, a focus was placed on systematic processes, including positioning, image acquisition, and structured reporting to monitor longitudinal change. The image-based monitoring procedure was applied to 6 Yucatan miniature pigs. A subset of animals (n= 3) were injected with crystalline silica into the apical bronchial tree to induce silicosis. The methodology provided longitudinal monitoring and evidence of progressive lung disease while simultaneously allowing for a cross-modality comparative study highlighting the practical application of medical image data collection in swine. The integration of multimodality imaging with structured reporting allows for cross comparison of modalities, refinement of CT and MRI protocols, and consistently monitors potential areas of interest for guided biopsy and/or necropsy. PMID- 26839329 TI - Regulatory Forum Opinion Piece*: Veterinary Pathologists in Translational Pharmacology and Biomarker Integration in Drug Discovery and Development. AB - This article highlights emerging roles for veterinary pathologists outside of traditional functions and in line with the translational research (TR) approach. Veterinary pathologists offer unique and valuable expertise toward addressing particular TR and associated translational pharmacology questions, identifying gaps and risks in biomarker and pathology strategies, and advancing TR team decision making. Veterinary pathologists' attributes that are integral to the TR approach include (i) well-developed understanding of comparative physiology, pathology, and disease; (ii) extensive experience in interpretation and integration of complex data sets on whole-body responses and utilizing this for deciphering pathogenesis and translating events between laboratory species and man; (iii) proficiency in recognizing differences in disease end points among individuals, animal species and strains, and assessing correlations between these differences and other investigative (including biomarker) findings; and (iv) strong background in a wide spectrum of research technologies that can address pathomechanistic questions and biomarker needs. Some of the more evident roles in which veterinary pathologists can offer their greatest contributions to address questions and strategies of TR and biomarker integration will be emphasized. PMID- 26839330 TI - A Brief Review of Infrequent Spontaneous Findings, Peculiar Anatomical Microscopic Features, and Potential Artifacts in Gottingen Minipigs. AB - Minipigs are now used in greater numbers in contract research organizations (CROs) as well as in the pharmaceutical industry. Most CROs or pharmaceutical companies use the Gottingen minipig, which displays a number of important background lesions. This review will discuss some of the more infrequent minipig background changes. Porcine stress syndrome is an autosomal recessive pharmacogenetic disorder in minipigs causing malignant hyperthermia and muscle necrosis. Possible triggers, clinical pathology as well as heart, muscle, liver, lung, and kidney histopathology are discussed. Additional spontaneous changes, background findings, and peculiar anatomical and histological features include thrombocytopenic purpura syndrome, spontaneous glomerulonephritis, osteochondritis, ellipsoids, or Schweigger-Seidel sheaths in the spleen, as well as the presence of a perimesenteric plexus adjacent to mesenteric lymph nodes, squamous epithelial metaplasia of the salivary gland, and cupping of the optic disk in the minipig eye. In order to maximize the data gained from minipig studies, the interpretation of pathology findings requires the input of experienced pathologists who understand the significance of artifacts and spontaneous, background lesions in minipigs and can distinguish these from induced lesions. PMID- 26839331 TI - Is Science the Only Driver in Species Selection? An Internal Study to Evaluate Compound Requirements in the Minipig Compared to the Dog in Preclinical Studies. AB - Dogs have been often chosen as a nonrodent species for preclinical development of small molecule drugs mainly due to availability and relative ease of handling. Recently, focus has increased on the minipig as a potential alternative to the dog, based on either scientific rationale or public opinion concerns. There are, however, other factors influencing nonrodent choices, in particular drug amount and synthesis time, which differ between species and therefore may impact the milestones of a drug development program. To assess the magnitude of compound need, a retrospective internal survey was conducted on drug amounts used in dog studies which were translated into the requirements for minipigs. Compound need approximately doubles if minipigs are used. Costs of compound are accordingly higher, and synthesis times are slightly increased. In our company, the differences were not considered significant enough to preclude the use of minipigs if the later preclinical program might benefit from improved human risk prediction. PMID- 26839332 TI - Carbon Nanotube and Asbestos Exposures Induce Overlapping but Distinct Profiles of Lung Pathology in Non-Swiss Albino CF-1 Mice. AB - Carbon nanotubes (CNTs) are emerging as important occupational and environmental toxicants owing to their increasing prevalence and potential to be inhaled as airborne particles. CNTs are a concern because of their similarities to asbestos, which include fibrous morphology, high aspect ratio, and biopersistence. Limitations in research models have made it difficult to experimentally ascertain the risk of CNT exposures to humans and whether these may lead to lung diseases classically associated with asbestos, such as mesothelioma and fibrosis. In this study, we sought to comprehensively compare profiles of lung pathology in mice following repeated exposures to multiwall CNTs or crocidolite asbestos (CA). We show that both exposures resulted in granulomatous inflammation and increased interstitial collagen; CA exposures caused predominantly bronchoalveolar hyperplasia, whereas CNT exposures caused alveolar hyperplasia of type II pneumocytes (T2Ps). T2Ps isolated from CNT-exposed lungs were found to have upregulated proinflammatory genes, including interleukin 1beta (IL-1beta), in contrast to those from CA exposed. Immunostaining in tissue showed that while both toxicants increased IL-1beta protein expression in lung cells, T2P-specific IL-1beta increases were greater following CNT exposure. These results suggest related but distinct mechanisms of action by CNTs versus asbestos which may lead to different outcomes in the 2 exposure types. PMID- 26839334 TI - Lipoprotein (a): Coming of Age at Last. PMID- 26839333 TI - Differential lipid metabolism in monocytes and macrophages: influence of cholesterol loading. AB - The influence of the hypercholesterolemia associated with atherosclerosis on monocytes is poorly understood. Monocytes are exposed to high concentrations of lipids, particularly cholesterol and lysophosphatidylcholine (lyso-PC). Indeed, in line with recent reports, we found that monocytes accumulate cholesteryl esters (CEs) in hypercholesterolemic mice, demonstrating the need for studies that analyze the effects of lipid accumulation on monocytes. Here we analyze the effects of cholesterol and lyso-PC loading in human monocytes and macrophages. We found that cholesterol acyltransferase and CE hydrolase activities are lower in monocytes. Monocytes also showed a different expression profile of cholesterol influx and efflux genes in response to lipid loading and a different pattern of lyso-PC metabolism. In monocytes, increased levels of CE slowed the conversion of lyso-PC into PC. Interestingly, although macrophages accumulated glycerophosphocholine, phosphocholine was the main water-soluble choline metabolite being generated in monocytes, suggesting a role for mono- and diacylglycerol in the chemoattractability of these cells. In summary, monocytes and macrophages show significant differences in lipid metabolism and gene expression profiles in response to lipid loading. These findings provide new insights into the mechanisms of atherosclerosis and suggest potentials for targeting monocyte chemotactic properties not only in atherosclerosis but also in other diseases. PMID- 26839335 TI - Description of the Female of Martinsmyia minasensis (Diptera, Psychodidae, Phlebotominae), With Distribution Records and a Key to Female Identification. AB - The adult female of the sand fly species Martinsmyia minasensis (Mangabeira, 1942) is described, and the characters of the genus Martinsmyia Galati, 1995 are defined. We performed morphometric analyses on the spermatheca and wings, and present data on the geographical distribution of M. minasensis, as well as an identification key to females of this genus. The specimens were measured, drawn, photographed, and compared with the similar species M. oliveirai. It was possible to distinguish between M. minasensis and M. oliveirai based on differences found in the common and individual ducts of the spermatheca, as well as wing shape and size. PMID- 26839336 TI - The Case for a Pre-Cancer Genome Atlas (PCGA). AB - Understanding the earliest molecular and cellular events associated with cancer initiation remains a key bottleneck to transforming our approach to cancer prevention and detection. While TCGA has provided unprecedented insights into the genomic events associated with advanced stage cancer, there have been few studies comprehensively profiling premalignant and early-stage disease or elucidating the role of the microenvironment in premalignancy and tumor initiation. In this article, we make a call for development of a "Pre-Cancer Genome Atlas (PCGA)," a concerted initiative to characterize the molecular alterations in premalignant lesions and the corresponding changes in the microenvironment associated with progression to invasive carcinoma. This initiative will require a multicenter coordinated effort to comprehensively profile (cellular and molecular) premalignant lesions and their corresponding "field of injury" collected longitudinally as the lesion progresses towards or regresses from frank malignancy across multiple tumor types. Genomic characterization of alterations in premalignant lesions and their microenvironment, for both bulk tissue and single cells, will enable development of biomarkers for early detection and risk stratification as well as allow for the development of novel targeted cancer interception strategies. The multi-institutional and multidisciplinary collaborative "big-data" effort underlying the PCGA will help usher in a new era of precision medicine for cancer detection and prevention. PMID- 26839337 TI - Europe's migration challenges: mounting an effective health system response. PMID- 26839338 TI - Europe's response to the refugee crisis: why relocation quotas will fail to achieve 'fairness' from a health perspective. PMID- 26839339 TI - European Public Health News. PMID- 26839340 TI - Hedgehog signalling. AB - The Hedgehog (Hh) signalling pathway is one of the key regulators of metazoan development. Hh proteins have been shown to play roles in many developmental processes and have become paradigms for classical morphogens. Dysfunction of the Hh pathway underlies a number of human developmental abnormalities and diseases, making it an important therapeutic target. Interest in Hh signalling thus extends across many fields, from evo-devo to cancer research and regenerative medicine. Here, and in the accompanying poster, we provide an outline of the current understanding of Hh signalling mechanisms, highlighting the similarities and differences between species. PMID- 26839341 TI - The force within: endocardial development, mechanotransduction and signalling during cardiac morphogenesis. AB - Endocardial cells are cardiac endothelial cells that line the interior of the heart tube. Historically, their contribution to cardiac development has mainly been considered from a morphological perspective. However, recent studies have begun to define novel instructive roles of the endocardium, as a sensor and signal transducer of biophysical forces induced by blood flow, and as an angiocrine signalling centre that is involved in myocardial cellular morphogenesis, regeneration and reprogramming. In this Review, we discuss how the endocardium develops, how endocardial-myocardial interactions influence the developing embryonic heart, and how the dysregulation of blood flow-responsive endocardial signalling can result in pathophysiological changes. PMID- 26839342 TI - View from the heart: cardiac fibroblasts in development, scarring and regeneration. AB - In the adult, tissue repair after injury is generally compromised by fibrosis, which maintains tissue integrity with scar formation but does not restore normal architecture and function. The process of regeneration is necessary to replace the scar and rebuild normal functioning tissue. Here, we address this problem in the context of heart disease, and discuss the origins and characteristics of cardiac fibroblasts, as well as the crucial role that they play in cardiac development and disease. We discuss the dual nature of cardiac fibroblasts, which can lead to scarring, pathological remodelling and functional deficit, but can also promote heart function in some contexts. Finally, we review current and proposed approaches whereby regeneration could be fostered by interventions that limit scar formation. PMID- 26839344 TI - Proper closure of the optic fissure requires ephrin A5-EphB2-JNK signaling. AB - The development of complex organs such as the eye requires a delicate and coordinated balance of cell division and cell death. Although apoptosis is prevalent in the proximoventral optic cup, the precise role it plays in eye development needs to be investigated further. In this study, we show that reduced apoptosis in the proximoventral optic cup prevents closure of the optic fissure. We also show that expression of ephrin A5 (Efna5) partially overlaps with Eph receptor B2 (Ephb2) expression in the proximoventral optic cup and that binding of EphB2 to ephrin A5 induces a sustained activation of JNK. This prolonged JNK signal promotes apoptosis and prevents cell proliferation. Thus, we propose that the unique cross-subclass interaction of EphB2 with ephrin A5 has evolved to function upstream of JNK signaling for the purpose of maintaining an adequate pool of progenitor cells to ensure proper closure of the optic fissure. PMID- 26839345 TI - Incidence of Diabetes in Colorectal Cancer Survivors. AB - BACKGROUND: A higher risk of colorectal cancer (CRC) in patients with diabetes has been well documented. However, little is known regarding diabetes incidence in CRC survivors. This may have substantial impact on CRC survivorship care as well as enhancing the understanding of the interplay between the two diseases. We explored whether the incidence of diabetes was higher among patients with CRC than matched control subjects. METHODS: Using population-based data from Ontario, Canada, we generated a dataset comprising 39 707 incident CRC cases and 198 535 age- and sex-matched control subjects (1:5) dating from April 2002 to March 2010. We used cause-specific hazard models to estimate the hazard ratios (HRs) for diabetes overall and in subgroups stratified by receipt of systemic chemotherapy, diagnosis of metastatic disease, and site of cancer. RESULTS: During a mean follow-up of 4.81 years, the association between CRC and diabetes varied: The rate of developing diabetes was 53% higher among CRC patients compared with control subjects in the first year postdiagnosis (HR = 1.53, 95% confidence interval [CI] = 1.42 to 1.64) and remained increased by 19% in the fifth year postdiagnosis (HR = 1.19, 95% CI = 1.05 to 1.35). Findings were similar in subgroups of patients who had colon cancer, received systemic chemotherapy, or had no evidence of metastasis. CONCLUSION: We found that CRC patients were statistically significantly more likely to develop subsequent diabetes than persons without CRC for up to five years after the diagnosis. Our study suggests that active screening and counseling regarding modifiable risk factors may be warranted in this high-risk group. PMID- 26839343 TI - WNT/beta-catenin signaling mediates human neural crest induction via a pre-neural border intermediate. AB - Neural crest (NC) cells arise early in vertebrate development, migrate extensively and contribute to a diverse array of ectodermal and mesenchymal derivatives. Previous models of NC formation suggested derivation from neuralized ectoderm, via meso-ectodermal, or neural-non-neural ectoderm interactions. Recent studies using bird and amphibian embryos suggest an earlier origin of NC, independent of neural and mesodermal tissues. Here, we set out to generate a model in which to decipher signaling and tissue interactions involved in human NC induction. Our novel human embryonic stem cell (ESC)-based model yields high proportions of multipotent NC cells (expressing SOX10, PAX7 and TFAP2A) in 5 days. We demonstrate a crucial role for WNT/beta-catenin signaling in launching NC development, while blocking placodal and surface ectoderm fates. We provide evidence of the delicate temporal effects of BMP and FGF signaling, and find that NC development is separable from neural and/or mesodermal contributions. We further substantiate the notion of a neural-independent origin of NC through PAX6 expression and knockdown studies. Finally, we identify a novel pre-neural border state characterized by early WNT/beta-catenin signaling targets that displays distinct responses to BMP and FGF signaling from the traditional neural border genes. In summary, our work provides a fast and efficient protocol for human NC differentiation under signaling constraints similar to those identified in vivo in model organisms, and strengthens a framework for neural crest ontogeny that is separable from neural and mesodermal fates. PMID- 26839347 TI - The Danish Girl. PMID- 26839346 TI - Immunotherapy Combined or Sequenced With Targeted Therapy in the Treatment of Solid Tumors: Current Perspectives. AB - The advent of newer immunotherapeutic and molecularly targeted agents has provided a number of effective options for cancer treatment but has also added much complexity in selecting the best initial treatment or treatment plan for each patient. Molecularly targeted agents offer selectivity and are the cornerstone for "precision medicine." While targeted agents are associated with high tumor response rates, patients inevitably develop resistance to these drugs. Immunotherapies exploit the endogenous immune system to eradicate cancer and can produce durable disease control that results in long-term, treatment-free survival in some patients. Guidelines for treatment selection in patients with specific tumor types and clinical features are routinely being reconsidered in order to accommodate the increasingly complex treatment landscapes. Here, we review current perspectives on the use of immunotherapeutic agents, particularly immune checkpoint inhibitors (nivolumab, pembrolizumab, and ipilimumab), in combination or in sequence with molecularly targeted agents in patients with advanced melanoma as well as other tumor types. We further discuss remaining unmet needs for patient selection and treatment with approved therapies. PMID- 26839348 TI - Incident Cerebral Microbleeds in a Cohort of Intracerebral Hemorrhage. AB - BACKGROUND AND PURPOSE: We aimed to identify prognostic and associated factors of incident cerebral microbleeds (CMBs) in intracerebral hemorrhage (ICH) survivors. METHODS: Observational prospective cohort of 168 ICH survivors who underwent 1.5T magnetic resonance imaging at ICH onset and during follow-up (median scan interval, 3.4; interquartile range, 1.4-4.7) years. We used logistic regression adjusted for age, sex, and scan interval. Analyses were stratified according to the index ICH location (58 lobar ICH, 103 nonlobar ICH, excluding patients with multiple or unclassifiable ICH). RESULTS: Eighty-nine (53%) patients had CMBs at ICH onset, and 80 (48%) exhibited incident CMBs during follow-up. Predictors of incident CMBs at ICH onset were >=1 CMBs (adjusted odds ratio [aOR], 2.27; 95% confidence interval [CI], 1.18-4.35), old radiological macrohemorrhage (aOR, 6.78; 95% CI, 2.76-16.68), and CMBs in mixed location (aOR, 3.73; 95% CI, 1.67 8.31). When stratifying by ICH location, incident CMBs were associated in nonlobar ICH with incident lacunes (aOR, 2.86; 95% CI, 1.04-7.85) and with the use of antiplatelet agents (aOR, 2.89; 95% CI, 1.14-7.32). In lobar ICH, incident CMBs were associated with incident radiological macrohemorrhage (aOR, 9.76; 95% CI, 1.07-88.77). CONCLUSIONS: Prognostic and associated factors of incident CMBs differed according to the index ICH location. Whereas in lobar ICH, incident CMBs were associated with hemorrhagic biomarkers, in nonlobar ICH, ischemic burden also increased. CMBs may be interesting biomarkers to monitor in randomized trials on restarting antithrombotic drugs after ICH. PMID- 26839349 TI - Organizational Update: Asia Pacific Stroke Organization. PMID- 26839350 TI - Documentation of Improved Outcomes for Intracranial Aneurysm Management Over a 15 Year Interval. AB - BACKGROUND AND PURPOSE: Despite rapid advancements in intracranial aneurysm management, there is no evidence as of yet that this has translated into improvement in overall prognosis. METHODS: We compared 2 periods of aneurysm management, 1998 to 2003 (n=1023 aneurysms) and 2007 to 2013 (n=1499 aneurysms), at a single, high-volume neurovascular center. Our outcome of interest was low or moderate disability (Glasgow Outcome Scale score of 4 or 5) at 6 months or more post treatment. RESULTS: There were significant improvements in outcome for surgical, endovascular, and overall treatment of unruptured (adjusted odds ratio [OR], 2.33; P=0.0091; adjusted OR, 4.40; P=0.0271; and adjusted OR, 2.58; P=0.0008, respectively) and ruptured (adjusted OR, 3.18; P=0.0004; adjusted OR, 3.54; P=0.0001; and adjusted OR, 3.11; P<0.0001, respectively) aneurysms from the first to the second time period. In 2007 to 2013, the proportion of cases with low or moderate disability at 6 months post subarachnoid hemorrhage was 75.6% for surgical clipping and 76.6% for endovascular therapy. CONCLUSIONS: We report significantly improved outcomes over time for overall aneurysm management and for multiple patient subgroups, associated with increased usage of endovascular therapy. PMID- 26839351 TI - Association of MTHFR C677T Genotype With Ischemic Stroke Is Confined to Cerebral Small Vessel Disease Subtype. AB - BACKGROUND AND PURPOSE: Elevated plasma homocysteine levels are associated with stroke. However, this might be a reflection of bias or confounding because trials have failed to demonstrate an effect from homocysteine lowering in stroke patients, although a possible benefit has been suggested in lacunar stroke. Genetic studies could potentially overcome these issues because genetic variants are inherited randomly and are fixed at conception. Therefore, we tested the homocysteine levels-associated genetic variant MTHFR C677T for association with magnetic resonance imaging-confirmed lacunar stroke and compared this with associations with large artery and cardioembolic stroke subtypes. METHODS: We included 1359 magnetic resonance imaging-confirmed lacunar stroke cases, 1824 large artery stroke cases, 1970 cardioembolic stroke cases, and 14 448 controls, all of European ancestry. Furthermore, we studied 3670 ischemic stroke patients in whom white matter hyperintensities volume was measured. We tested MTHFR C677T for association with stroke subtypes and white matter hyperintensities volume. Because of the established association of homocysteine with hypertension, we additionally stratified for hypertension status. RESULTS: MTHFR C677T was associated with lacunar stroke (P=0.0003) and white matter hyperintensity volume (P=0.04), but not with the other stroke subtypes. Stratifying the lacunar stroke cases for hypertension status confirmed this association in hypertensive individuals (P=0.0002), but not in normotensive individuals (P=0.30). CONCLUSIONS: MTHFR C677T was associated with magnetic resonance imaging-confirmed lacunar stroke, but not large artery or cardioembolic stroke. The association may act through increased susceptibility to, or interaction with, high blood pressure. This heterogeneity of association might explain the lack of effect of lowering homocysteine in secondary prevention trials which included all strokes. PMID- 26839353 TI - Combining Growth Factor and Bone Marrow Cell Therapy Induces Bleeding and Alters Immune Response After Stroke in Mice. AB - BACKGROUND AND PURPOSE: Bone marrow cell (BMC)-based therapies, either the transplantation of exogenous cells or stimulation of endogenous cells by growth factors like the granulocyte colony-stimulating factor (G-CSF), are considered a promising means of treating stroke. In contrast to large preclinical evidence, however, a recent clinical stroke trial on G-CSF was neutral. We, therefore, aimed to investigate possible synergistic effects of co-administration of G-CSF and BMCs after experimental stroke in mice to enhance the efficacy compared with single treatments. METHODS: We used an animal model for experimental stroke as paradigm to study possible synergistic effects of co-administration of G-CSF and BMCs on the functional outcome and the pathophysiological mechanism. RESULTS: G CSF treatment alone led to an improved functional outcome, a reduced infarct volume, increased blood vessel stabilization, and decreased overall inflammation. Surprisingly, the combination of G-CSF and BMCs abrogated G-CSFs' beneficial effects and resulted in increased hemorrhagic infarct transformation, altered blood-brain barrier, excessive astrogliosis, and altered immune cell polarization. These increased rates of infarct bleeding were mainly mediated by elevated matrix metalloproteinase-9-mediated blood-brain barrier breakdown in G CSF- and BMCs-treated animals combined with an increased number of dilated and thus likely more fragile vessels in the subacute phase after cerebral ischemia. CONCLUSIONS: Our results provide new insights into both BMC-based therapies and immune cell biology and help to understand potential adverse and unexpected side effects. PMID- 26839352 TI - Endothelial Cells Lining Sporadic Cerebral Cavernous Malformation Cavernomas Undergo Endothelial-to-Mesenchymal Transition. AB - BACKGROUND AND PURPOSE: Cerebral cavernous malformation (CCM) is characterized by multiple lumen vascular malformations in the central nervous system that can cause neurological symptoms and brain hemorrhages. About 20% of CCM patients have an inherited form of the disease with ubiquitous loss-of-function mutation in any one of 3 genes CCM1, CCM2, and CCM3. The rest of patients develop sporadic vascular lesions histologically similar to those of the inherited form and likely mediated by a biallelic acquired mutation of CCM genes in the brain vasculature. However, the molecular phenotypic features of endothelial cells in CCM lesions in sporadic patients are still poorly described. This information is crucial for a targeted therapy. METHODS: We used immunofluorescence microscopy and immunohistochemistry to analyze the expression of endothelial-to-mesenchymal transition markers in the cavernoma of sporadic CCM patients in parallel with human familial cavernoma as a reference control. RESULTS: We report here that endothelial cells, a cell type critically involved in CCM development, undergo endothelial-to-mesenchymal transition in the lesions of sporadic patients. This switch in endothelial phenotype has been described only in genetic CCM patients and in murine models of the disease. In addition, TGF-beta/p-Smad- and beta catenin-dependent signaling pathways seem activated in sporadic cavernomas as in familial ones. CONCLUSIONS: Our findings support the use of common therapeutic strategies for both sporadic and genetic CCM malformations. PMID- 26839354 TI - Relationship Between Collateral Status, Contrast Transit, and Contrast Density in Acute Ischemic Stroke. AB - BACKGROUND AND PURPOSE: Collateral circulation is recognized to influence the life expectancy of the ischemic penumbra in acute ischemic stroke. The best method to quantify collateral status on acute imaging is uncertain. We aimed to determine the relationship between visual collateral status, quantitative collateral assessments, baseline computed tomographic perfusion measures, and tissue outcomes on follow-up imaging. METHODS: Sixty-six consecutive patients with acute ischemic stroke clinically eligible for recanalization therapy and with M1 or M2 middle cerebral artery occlusion were evaluated. We compared the visual collateral scoring with measures of contrast peak time delay and contrast peak density. We also compared these measures for their ability to predict perfusion lesion and infarct core volumes, final infarct, and infarct growth. RESULTS: Shorter contrast peak time delay (P=0.041) and higher contrast peak density (P=0.002) were associated with good collateral status. Shorter contrast peak time delay correlated with higher contrast peak density (beta=-4.413; P=0.037). In logistic regression analysis after adjustment for age, sex, onset computed tomographic time, and occlusion site, higher contrast peak density was independently associated with good collateral status (P=0.009). Multiple regression analysis showed that higher contrast peak density was an independent predictor of smaller perfusion lesion volume (P=0.029), smaller ischemic core volume (P=0.044), smaller follow-up infarct volume (P=0.005), and smaller infarct growth volume (P=0.010). CONCLUSIONS: Visual collateral status, contrast peak density, and contrast peak time delay were inter-related, and good collateral status was strongly associated with contrast peak density. Contrast peak density in collateral vessel may be an important factor in tissue fate in acute ischemic stroke. PMID- 26839355 TI - Matrix Metalloprotease 3 Exacerbates Hemorrhagic Transformation and Worsens Functional Outcomes in Hyperglycemic Stroke. AB - BACKGROUND AND PURPOSE: Acute hyperglycemia worsens the clinical outcomes and exacerbates cerebral hemorrhage after stroke. The mediators of hemorrhagic transformation (HT) in hyperglycemic stroke are not fully understood. Matrix metalloproteinase 3 (MMP3) plays a critical role in the tissue-type plasminogen activator-induced HT. However, the role of MMP3 in exacerbating the HT and worsening the functional outcomes in hyperglycemic stroke remains unknown. METHODS: Control/normoglycemic and hyperglycemic (blood glucose, 140-200 mg/dL) male Wistar rats were subjected to middle cerebral artery occlusion for 90 minutes and either 24 hours or 7 days reperfusion. MMP3 was inhibited pharmacologically (UK 356618, 15 mg/kg IV at reperfusion) or knocked down in the brain by shRNA lentiviral particles (injected intracerebroventricular). Neurovascular injury was assessed at 24 hours, and functional outcomes were assessed at 24 hours, day 3, and day 7. MMP3 activity was measured in brain homogenate and cerebral macrovessels. Localization of MMP3 within the neurovascular unit after hyperglycemic stroke was demonstrated by immunohistochemistry. RESULTS: Hyperglycemia significantly increased MMP3 activity in the brain after stroke, and this was associated with exacerbated HT and worsened functional outcomes. MMP3 inhibition significantly reduced HT and improved functional outcomes. CONCLUSIONS: MMP3 plays a critical role in mediating cerebrovascular injury in hyperglycemic stroke. Our findings point out MMP3 as a potential therapeutic target in hyperglycemic stroke. PMID- 26839357 TI - Transcriptome Analysis of Murine Olfactory Sensory Neurons during Development Using Single Cell RNA-Seq. AB - Mammalian odor reception is achieved by highly specialized olfactory sensory neurons (OSNs) located in the nasal cavity. Despite their importance for the daily survival of most mammals, the gene expression and regulatory profiles of these single neurons are poorly understood. Here, we report the isolation of individual GFP-labeled OSNs from Olfr73-GFP mice at different developmental stages followed by Next Generation Sequencing, thereby analyzing the detailed transcriptome for the first time. We characterized the repertoire of olfactory receptors (ORs) and found that in addition to the highly and predominant detectable Olfr73, 20 additional ORs were stably detectable at lower transcript levels in adult mice. Additionally, OSNs collected from mice of earlier developmental stages did not show any stable OR patterns. However, more than one predominant OR per OSN was detectable. PMID- 26839358 TI - A Review of Michael Stoddart. PMID- 26839356 TI - Efficacy of Adjuvant Chemotherapy in Colon Cancer With Microsatellite Instability: A Large Multicenter AGEO Study. AB - BACKGROUND: Deficient mismatch repair (dMMR) colon cancer (CC) is reportedly resistant to 5-fluorouracil (5FU) adjuvant chemotherapy while preliminary data suggest chemosensitivity to oxaliplatin. We assessed the efficacy of fluoropyrimidine with and without oxaliplatin in a large cohort of dMMR CC patients. METHODS: This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for stage II or III dMMR CC between 2000 and 2011. Prognostic factors were analyzed using Cox models, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. RESULTS: A total of 433 dMMR CC patients were included (56.8% stage II, 43.2% stage III). Mean follow-up was 47.0 months. The patients received surgery alone (n = 263) or surgery plus adjuvant chemotherapy consisting of fluoropyrimidine with (n = 119) or without (n = 51) oxaliplatin. Adjuvant chemotherapy was administered to 16.7% of stage II and 69.0% of stage III CC patients. As compared with surgery alone, adjuvant oxaliplatin-based chemotherapy improved disease-free survival (DFS) in multivariable analysis (HR = 0.35, 95% CI = 0.19 to 0.65, P < .001), contrary to adjuvant fluoropyrimidine alone (HR = 0.73, 95% CI = 0.36 to 1.49, P = .38). In the subgroup analysis, the DFS benefit of oxaliplatin-based chemotherapy was statistically significant in multivariable analysis only in stage III (HR = 0.41, 95% CI = 0.19 to 0.87, P = .02). CONCLUSION: This study supports the use of adjuvant chemotherapy with fluoropyrimidine plus oxaliplatin in stage III dMMR CC. PMID- 26839359 TI - Cigarette smokers have exaggerated alveolar barrier disruption in response to lipopolysaccharide inhalation. AB - RATIONALE: Cigarette smoke exposure is associated with an increased risk of the acute respiratory distress syndrome (ARDS); however, the mechanisms underlying this relationship remain largely unknown. OBJECTIVE: To assess pathways of lung injury and inflammation in smokers and non-smokers with and without lipopolysaccharide (LPS) inhalation using established biomarkers. METHODS: We measured plasma and bronchoalveolar lavage (BAL) biomarkers of inflammation and lung injury in smokers and non-smokers in two distinct cohorts of healthy volunteers, one unstimulated (n=20) and one undergoing 50 MUg LPS inhalation (n=30). MEASUREMENTS AND MAIN RESULTS: After LPS inhalation, cigarette smokers had increased alveolar-capillary membrane permeability as measured by BAL total protein, compared with non-smokers (median 274 vs 208 MUg/mL, p=0.04). Smokers had exaggerated inflammation compared with non-smokers, with increased BAL interleukin-1beta (p=0.002), neutrophils (p=0.02), plasma interleukin-8 (p=0.003), and plasma matrix metalloproteinase-8 (p=0.006). Alveolar epithelial injury after LPS was more severe in smokers than non-smokers, with increased plasma (p=0.04) and decreased BAL (p=0.02) surfactant protein D. Finally, smokers had decreased BAL vascular endothelial growth factor (VEGF) (p<0.0001) with increased soluble VEGF receptor-1 (p=0.0001). CONCLUSIONS: Cigarette smoke exposure may predispose to ARDS through an abnormal response to a 'second hit,' with increased alveolar-capillary membrane permeability, exaggerated inflammation, increased epithelial injury and endothelial dysfunction. LPS inhalation may serve as a useful experimental model for evaluation of the acute pulmonary effects of existing and new tobacco products. PMID- 26839360 TI - A patient with complex multiple genomic ALK alterations. PMID- 26839361 TI - Calsyntenin 1-mediated trafficking of axon guidance receptors regulates the switch in axonal responsiveness at a choice point. AB - Axon guidance at choice points depends on the precise regulation of guidance receptors on the growth cone surface. Upon arrival at the intermediate target or choice point, a switch from attraction to repulsion is required for the axon to move on. Dorsal commissural (dI1) axons crossing the ventral midline of the spinal cord in the floor plate represent a convenient model for the analysis of the molecular mechanism underlying the switch in axonal behavior. We identified in chick a role for calsyntenin 1 in the regulation of vesicular trafficking of guidance receptors in dI1 axons at choice points. In cooperation with RabGDI, calsyntenin 1 shuttles Rab11-positive vesicles containing Robo1 to the growth cone surface in a precisely regulated manner. By contrast, calsyntenin 1-mediated trafficking of frizzled 3, a guidance receptor in the Wnt pathway, is independent of RabGDI. Thus, tightly regulated insertion of guidance receptors, which is required for midline crossing and the subsequent turn into the longitudinal axis, is achieved by specific trafficking. PMID- 26839362 TI - Rab8 directs furrow ingression and membrane addition during epithelial formation in Drosophila melanogaster. AB - One of the most fundamental changes in cell morphology is the ingression of a plasma membrane furrow. The Drosophila embryo undergoes several cycles of rapid furrow ingression during early development that culminate in the formation of an epithelial sheet. Previous studies have demonstrated the requirement for intracellular trafficking pathways in furrow ingression; however, the pathways that link compartmental behaviors with cortical furrow ingression events are unclear. Here, we show that Rab8 has striking dynamic behaviors in vivo. As furrows ingress, cytoplasmic Rab8 puncta are depleted and Rab8 accumulates at the plasma membrane in a location that coincides with known regions of directed membrane addition. We additionally use CRISPR/Cas9 technology to N-terminally tag Rab8, which is then used to address endogenous localization and function. Endogenous Rab8 displays partial coincidence with Rab11 and the Golgi, and this colocalization is enriched during the fast phase of cellularization. When Rab8 function is disrupted, furrow formation in the early embryo is completely abolished. We also demonstrate that Rab8 behaviors require the function of the exocyst complex subunit Sec5 as well as the recycling endosome protein Rab11. Active, GTP-locked Rab8 is primarily associated with dynamic membrane compartments and the plasma membrane, whereas GDP-locked Rab8 forms large cytoplasmic aggregates. These studies suggest a model in which active Rab8 populations direct furrow ingression by guiding the targeted delivery of cytoplasmic membrane stores to the cell surface through interactions with the exocyst tethering complex. PMID- 26839363 TI - Endothelial cell specification in the somite is compromised in Pax3-positive progenitors of Foxc1/2 conditional mutants, with loss of forelimb myogenesis. AB - Pax3 and Foxc2 have been shown genetically to mutually repress each other in the mouse somite. Perturbation of this balance in multipotent cells of the dermomyotome influences cell fate; upregulation of Foxc2 favours a vascular fate, whereas higher levels of Pax3 lead to myogenesis. Foxc1 has overlapping functions with Foxc2. In Foxc1/2 double-mutant embryos, somitogenesis is severely affected, precluding analysis of somite derivatives. We have adopted a conditional approach whereby mutations in Foxc1 and Foxc2 genes were targeted to Pax3-expressing cells. Inclusion of a conditional reporter allele in the crosses made it possible to follow cells that had expressed Pax3. At the forelimb level, endothelial and myogenic cells migrate from adjacent somites into the limb bud. This population of endothelial cells is compromised in the double mutant, whereas excessive production of myogenic cells is observed in the trunk. However, strikingly, myogenic progenitors fail to enter the limbs, leading to the absence of skeletal muscle. Pax3-positive migratory myogenic progenitors, marked by expression of Lbx1, are specified in the somite at forelimb level, but endothelial progenitors are absent. The myogenic progenitors do not die, but differentiate prematurely adjacent to the somite. We conclude that the small proportion of somite-derived endothelial cells in the limb is required for the migration of myogenic limb progenitors. PMID- 26839364 TI - Mammary epithelial tubes elongate through MAPK-dependent coordination of cell migration. AB - Mammary branching morphogenesis is regulated by receptor tyrosine kinases (RTKs). We sought to determine how these RTK signals alter proliferation and migration to accomplish tube elongation in mouse. Both behaviors occur but it has been difficult to determine their relative contribution to elongation in vivo, as mammary adipocytes scatter light and limit the depth of optical imaging. Accordingly, we utilized 3D culture to study elongation in an experimentally accessible setting. We first used antibodies to localize RTK signals and discovered that phosphorylated ERK1/2 (pERK) was spatially enriched in cells near the front of elongating ducts, whereas phosphorylated AKT was ubiquitous. We next observed a gradient of cell migration speeds from rear to front of elongating ducts, with the front characterized by both high pERK and the fastest cells. Furthermore, cells within elongating ducts oriented both their protrusions and their migration in the direction of tube elongation. By contrast, cells within the organoid body were isotropically protrusive. We next tested the requirement for proliferation and migration. Early inhibition of proliferation blocked the creation of migratory cells, whereas late inhibition of proliferation did not block continued duct elongation. By contrast, pharmacological inhibition of either MEK or Rac1 signaling acutely blocked both cell migration and duct elongation. Finally, conditional induction of MEK activity was sufficient to induce collective cell migration and ductal elongation. Our data suggest a model for ductal elongation in which RTK-dependent proliferation creates motile cells with high pERK, the collective migration of which acutely requires both MEK and Rac1 signaling. PMID- 26839365 TI - The late and dual origin of cerebrospinal fluid-contacting neurons in the mouse spinal cord. AB - Considerable progress has been made in understanding the mechanisms that control the production of specialized neuronal types. However, how the timing of differentiation contributes to neuronal diversity in the developing spinal cord is still a pending question. In this study, we show that cerebrospinal fluid contacting neurons (CSF-cNs), an anatomically discrete cell type of the ependymal area, originate from surprisingly late neurogenic events in the ventral spinal cord. CSF-cNs are identified by the expression of the transcription factors Gata2 and Gata3, and the ionic channels Pkd2l1 and Pkd1l2. Contrasting with Gata2/3(+) V2b interneurons, differentiation of CSF-cNs is independent of Foxn4 and takes place during advanced developmental stages previously assumed to be exclusively gliogenic. CSF-cNs are produced from two distinct dorsoventral regions of the mouse spinal cord. Most CSF-cNs derive from progenitors circumscribed to the late p2 and the oligodendrogenic (pOL) domains, whereas a second subset of CSF-cNs arises from cells bordering the floor plate. The development of these two subgroups of CSF-cNs is differentially controlled by Pax6, they adopt separate locations around the postnatal central canal and they display electrophysiological differences. Our results highlight that spatiotemporal mechanisms are instrumental in creating neural cell diversity in the ventral spinal cord to produce distinct classes of interneurons, motoneurons, CSF-cNs, glial cells and ependymal cells. PMID- 26839366 TI - MicroRNA-23b Targets Ras GTPase-Activating Protein SH3 Domain-Binding Protein 2 to Alleviate Fibrosis and Albuminuria in Diabetic Nephropathy. AB - Diabetic nephropathy (DN) is a frequent and severe complication of diabetes that is structurally characterized by glomerular basement membrane thickening, extracellular matrix accumulation, and destabilization of podocyte foot processes. MicroRNAs (miRNAs) are dysregulated in DN, but identification of the specific miRs involved remains incomplete. Here, we confirm that the peripheral blood from patients with diabetes and the kidneys of animals with type 1 or 2 diabetes have low levels of miR-23b compared with those of their nondiabetic counterparts. Furthermore, exposure to high glucose downregulated miR-23b in cultured kidney cells. In contrast, renal expression of Ras GTPase-activating protein SH3 domain-binding protein 2 (G3BP2), a putative miR-23b target, increased in DN. In vitro, overexpression of miR-23b decreased, and inhibition of miR-23b increased, G3BP2 expression levels. Bioinformatics analysis also revealed p53 binding sites in the miR-23b promoter; in vitro inhibition of p53 or the upstream p38 mitogen-activated protein kinase (p38MAPK) upregulated miR-23b expression in high-glucose conditions. In turn, inhibition of G3BP2 or overexpression of miR-23b downregulated p53 and p38MAPK expression in high glucose conditions. In vivo, overexpression of miR-23b or inhibition of p53 in db/db mice reversed hyperalbuminuria and kidney fibrosis, whereas miR-23b antagomir treatment promoted renal fibrosis and increased albuminuria in wild type mice. These data suggest that hyperglycemia regulates pathogenic processes in DN through an miR-23b/G3BP2 feedback circuit involving p38MAPK and p53. In conclusion, these results reveal a role for miR-23b in DN and indicate a novel potential therapeutic target. PMID- 26839367 TI - Role of Receptor Protein Tyrosine Phosphatase gamma in Sensing Extracellular CO2 and HCO3. AB - Regulation of blood pH-critical for virtually every facet of life-requires that the renal proximal tubule (PT) adjust its rate of H(+) secretion (nearly the same as the rate of HCO3 (-) reabsorption, JHCO3 ) in response to changes in blood [CO2] and [HCO3 (-)]. Yet CO2/HCO3 (-) sensing mechanisms remain poorly characterized. Because receptor tyrosine kinase inhibitors render JHCO3 in the PT insensitive to changes in CO2 concentration, we hypothesized that the structural features of receptor protein tyrosine phosphatase-gamma (RPTPgamma) that are consistent with binding of extracellular CO2 or HCO3 (-) facilitate monitoring of blood CO2/HCO3 (-) concentrations. We now report that PTs express RPTPgamma on blood-facing membranes. Moreover, RPTPgamma deletion in mice eliminated the CO2 and HCO3 (-) sensitivities of JHCO3 as well as the normal defense of blood pH during whole-body acidosis. Thus, RPTPgamma appears to be a novel extracellular CO2/HCO3 (-) sensor critical for pH homeostasis. PMID- 26839369 TI - Quantification of Flavin-containing Monooxygenases 1, 3, and 5 in Human Liver Microsomes by UPLC-MRM-Based Targeted Quantitative Proteomics and Its Application to the Study of Ontogeny. AB - Flavin-containing monooxygenases (FMOs) have a significant role in the metabolism of small molecule pharmaceuticals. Among the five human FMOs, FMO1, FMO3, and FMO5 are the most relevant to hepatic drug metabolism. Although age-dependent hepatic protein expression, based on immunoquantification, has been reported previously for FMO1 and FMO3, there is very little information on hepatic FMO5 protein expression. To overcome the limitations of immunoquantification, an ultra performance liquid chromatography (UPLC)-multiple reaction monitoring (MRM)-based targeted quantitative proteomic method was developed and optimized for the quantification of FMO1, FMO3, and FMO5 in human liver microsomes (HLM). A post-in silico product ion screening process was incorporated to verify LC-MRM detection of potential signature peptides before their synthesis. The developed method was validated by correlating marker substrate activity and protein expression in a panel of adult individual donor HLM (age 39-67 years). The mean (range) protein expression of FMO3 and FMO5 was 46 (26-65) pmol/mg HLM protein and 27 (11.5-49) pmol/mg HLM protein, respectively. To demonstrate quantification of FMO1, a panel of fetal individual donor HLM (gestational age 14-20 weeks) was analyzed. The mean (range) FMO1 protein expression was 7.0 (4.9-9.7) pmol/mg HLM protein. Furthermore, the ontogenetic protein expression of FMO5 was evaluated in fetal, pediatric, and adult HLM. The quantification of FMO proteins also was compared using two different calibration standards, recombinant proteins versus synthetic signature peptides, to assess the ratio between holoprotein versus total protein. In conclusion, a UPLC-MRM-based targeted quantitative proteomic method has been developed for the quantification of FMO enzymes in HLM. PMID- 26839368 TI - Far Upstream Element-Binding Protein 1 Binds the 3' Untranslated Region of PKD2 and Suppresses Its Translation. AB - Autosomal dominant polycystic kidney disease pathogenesis can be recapitulated in animal models by gene mutations in or dosage alterations of polycystic kidney disease 1 (PKD1) or PKD2, demonstrating that too much and too little PKD1/PKD2 are both pathogenic. Gene dosage manipulation has become an appealing approach by which to compensate for loss or gain of gene function, but the mechanisms controlling PKD2 expression remain incompletely characterized. In this study, using cultured mammalian cells and dual-luciferase assays, we found that the 3' untranslated region (3'UTR) of PKD2 mRNA inhibits luciferase protein expression. We then identified nucleotides 691-1044, which we called 3FI, as the 3'UTR fragment necessary for repressing the expression of luciferase or PKD2 in this system. Using a pull-down assay and mass spectrometry we identified far upstream element-binding protein 1 (FUBP1) as a 3FI-binding protein. In vitro overexpression of FUBP1 inhibited the expression of PKD2 protein but not mRNA. In embryonic zebrafish, FUBP1 knockdown (KD) by morpholino injection increased PKD2 expression and alleviated fish tail curling caused by morpholino-mediated KD of PKD2. Conversely, FUBP1 overexpression by mRNA injection significantly increased pronephric cyst occurrence and tail curling in zebrafish embryos. Furthermore, FUBP1 binds directly to eukaryotic translation initiation factor 4E-binding protein 1, indicating a link to the translation initiation complex. These results show that FUBP1 binds 3FI in the PKD2 3'UTR to inhibit PKD2 translation, regulating zebrafish disease phenotypes associated with PKD2 KD. PMID- 26839370 TI - Superficial Echogenic Lesions Detected on Neonatal Cranial Sonography: Possible Indicators of Severe Birth Injury. AB - OBJECTIVES: The purpose of this study was to evaluate the characteristics and importance of superficial echogenic lesions around cranial sutures on neonatal cranial sonography. METHODS: We retrospectively reviewed the clinical records and neuroimaging studies of 40 neonates who had superficial echogenic lesions around sutures on neonatal cranial sonography. Magnetic resonance imaging (n = 18) and computed tomography (n = 2) were performed within 2 weeks after sonography. We correlated sonographic findings with computed tomographic and magnetic resonance imaging findings and analyzed them. We also evaluated the associated lesions, neurologic signs, and follow-up changes. RESULTS: Sonographically, the superficial echogenic lesions involved both sulci and perisulcal parenchyma in 39 neonates and were located in the frontal and parietal areas around the sagittal suture in 38 neonates. Magnetic resonance imaging revealed a pattern of hypoxic ischemic encephalopathy in 9 neonates, birth trauma in 3 neonates, a mixed pattern of hypoxic ischemic encephalopathy and trauma in 3 neonates, nonspecific single infarctions in 2 neonates, and lack of a defined lesion in 1 neonate. The associated lesions were subdural hemorrhage (n = 12), epidural hematoma (n = 4), germinal matrix hemorrhage (n = 3), intraventricular hemorrhage (n = 2), and periventricular leukomalacia (n = 1). All epidural hematomas were associated with scalp hematoma, and 2 patients had skull fractures. One neonate with epidural hematoma associated with a hypoxic ischemic encephalopathy pattern showed mild spasticity in both ankles until 16 months. CONCLUSIONS: Superficial echogenic lesions detected around cranial sutures on neonatal sonography may be an indicator of more serious intracranial lesions such as more extensive hypoxic ischemic encephalopathy and intracranial hematomas, including epidural hematoma. PMID- 26839371 TI - Contrast-Enhanced Sonographic Follow-up After Stenting of Visceral Artery Aneurysms. AB - We report 2 cases of exclusion of visceral artery aneurysms. The first was a common hepatic artery aneurysm treated with a multilayer stent; the second was a celiac trunk aneurysm excluded by a covered stent. Computed tomographic angiography was performed at regular intervals after each procedure, together with echo color Doppler imaging and contrast-enhanced sonography. Computed tomographic angiography and contrast-enhanced sonography were able to detect endoleaks in both patients and the related inflow vessel; moreover, diameter measurements of the sacs were identical. In our preliminary experience, contrast enhanced sonography appeared to be as accurate as computed tomographic angiography after endovascular visceral artery aneurysm exclusion. PMID- 26839372 TI - Off-Label Use of Ultrasound Contrast Agents for Intravenous Applications in Children: Analysis of the Existing Literature. AB - OBJECTIVES: The purpose of this study was to collect and analyze the published data related to intravenous (IV) use of ultrasound (US) contrast agents in children. METHODS: We searched the literature to collect all of the published studies reporting the IV administration of a second-generation US contrast agent in children. RESULTS: We analyzed 9 case series and 5 case reports, as well as 5 individual cases, of pediatric contrast-enhanced US use reported in a study group that also included adults. We found that 502 children underwent contrast-enhanced US examinations (mean age, 9.7 years; range, 1 day-18 years). Most patients (89%) were injected with the sulfur hexafluoride contrast agent SonoVue (Bracco SpA, Milan, Italy). The mean dose used was 1.5 mL (range, 0.1-9.6 mL). Only 10 patients (2%) had adverse reactions related to the contrast agent administration: 1 life-threatening anaphylactic shock and 9 mild transitory adverse effects. We additionally found 38 papers in which the study groups included at least 1 child; thus, we obtained a total of 540 reported cases of off-label use of IV US contrast agents in children. The most frequent target organ was the liver, and most indications were related to space-occupying lesion characterization and abdominal evaluations after blunt trauma. Some studies also evaluated the diagnostic performance of contrast-enhanced US in different clinical scenarios and found very good accuracy. Concordance between contrast-enhanced US imaging and the respective reference-standard imaging methods ranged between 83% and 100% in different studies. CONCLUSIONS: Our results support the idea that the IV use of US contrast agents in children is safe, feasible, diagnostically robust, and effective. PMID- 26839373 TI - Prenatal Visualization of the Pulmonary and Aortic Valves and Leaflets Is Feasible Using 4-Dimensional Sonography. AB - OBJECTIVES: The purpose of this study was to determine whether the morphologic characteristics and area of the semilunar valves in healthy fetuses and fetuses with cardiac defects can be visualized by using spatiotemporal image correlation (STIC). METHODS: Spatiotemporal image correlation volumes from 74 healthy fetuses were recorded in 5 examinations between the 15th and 36th weeks of pregnancy. Second, we recorded STIC volumes from 64 fetuses with various cardiac defects. The quality of the volumes was rated. The areas of the aortic and pulmonary valves were measured in systole by rendering the valves on 4-dimensional sonography. The number of leaflets was examined. Longitudinal data analysis using linear mixed models was performed. RESULTS: Two hundred ninety-three volumes from normal hearts were examined. In 82.5%, the quality of the normal volumes was sufficient. Visualization of the valve opening was feasible in 96.1% of the normal hearts and 97.4% of the abnormal hearts. The success rate of visualization of the pulmonary and aortic valve leaflets was dependent on the gestational age, with the highest percentage (72.1% in normal hearts) at 19 to 24 weeks. Longitudinal regression analysis showed a positive relationship of the aortic and pulmonary valve areas with gestational age (P < .0001) and fetal biometric measurements (P < .0001). Fifty-eight abnormal volumes were examined. Cardiac defects with abnormal valve areas due to aortic and pulmonary stenosis could be clearly visualized by using STIC. CONCLUSIONS: Examination of the morphologic characteristics of the semilunar valves using STIC is feasible, which is difficult when using 2-dimensional sonography. With increasing implementation of 4-dimensional sonography, the understanding of rendered images might be useful for anyone practicing fetal echocardiography. PMID- 26839374 TI - A Comparative Study of Surgical Splenectomy, Partial Splenic Embolization, and High-Intensity Focused Ultrasound for Hypersplenism. AB - OBJECTIVES: This study compared splenectomy, partial splenic embolization, and high-intensity focused ultrasound (HIFU) therapy, which represent the traditional, mature, and newest methods for improving thrombocytopenia in hypersplenism, respectively. METHODS: A total of 69 patients with hypersplenism were treated with surgical splenectomy (n = 31), HIFU (n = 26), or partial splenic embolization (n = 12). They were followed closely for at least 6 months, and the effectiveness of the treatments was compared. RESULTS: Among the 3 groups, splenectomy was the most effective treatment for increasing peripheral blood cells. Embolization reduced the operating time and hospital stay, but HIFU was relatively safer and less invasive than the other treatments. CONCLUSIONS: High-intensity focused ultrasound has wide clinical indications for hypersplenism and may be safer than other treatment methods. Therefore, it is a good alternative procedure for patients with a high surgical risk. PMID- 26839375 TI - Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems. AB - Medium-chain triglycerides have been used as part of a ketogenic diet effective in reducing epileptic episodes. The health benefits of the derived medium-chain fatty acids (MCFAs) are thought to result from the stimulation of liver ketogenesis providing fuel for the brain. We tested whether MCFAs have direct effects on energy metabolism in induced pluripotent stem cell-derived human astrocytes and neurons. Using single-cell imaging, we observed an acute pronounced reduction of the mitochondrial electrical potential and a concomitant drop of the NAD(P)H signal in astrocytes, but not in neurons. Despite the observed effects on mitochondrial function, MCFAs did not lower intracellular ATP levels or activate the energy sensor AMP-activated protein kinase. ATP concentrations in astrocytes were unaltered, even when blocking the respiratory chain, suggesting compensation through accelerated glycolysis. The MCFA decanoic acid (300 MUM) promoted glycolysis and augmented lactate formation by 49.6%. The shorter fatty acid octanoic acid (300 MUM) did not affect glycolysis but increased the rates of astrocyte ketogenesis 2.17-fold compared with that of control cells. MCFAs may have brain health benefits through the modulation of astrocyte metabolism leading to activation of shuttle systems that provide fuel to neighboring neurons in the form of lactate and ketone bodies.-Thevenet, J., De Marchi, U., Santo Domingo, J., Christinat, N., Bultot, L., Lefebvre, G., Sakamoto, K., Descombes, P., Masoodi, M., Wiederkehr, A. Medium-chain fatty acids inhibit mitochondrial metabolism in astrocytes promoting astrocyte-neuron lactate and ketone body shuttle systems. PMID- 26839376 TI - Salmonella employs multiple mechanisms to subvert the TLR-inducible zinc-mediated antimicrobial response of human macrophages. AB - We aimed to characterize antimicrobial zinc trafficking within macrophages and to determine whether the professional intramacrophage pathogen Salmonella enterica serovar Typhimurium (S Typhimurium) subverts this pathway. Using both Escherichia coli and S Typhimurium, we show that TLR signaling promotes the accumulation of vesicular zinc within primary human macrophages. Vesicular zinc is delivered to E. coli to promote microbial clearance, whereas S. Typhimurium evades this response via Salmonella pathogenicity island (SPI)-1. Even in the absence of SPI 1 and the zinc exporter ZntA, S Typhimurium resists the innate immune zinc stress response, implying the existence of additional host subversion mechanisms. We also demonstrate the combinatorial antimicrobial effects of zinc and copper, a pathway that S. Typhimurium again evades. Our use of complementary tools and approaches, including confocal microscopy, direct assessment of intramacrophage bacterial zinc stress responses, specific E. coli and S Typhimurium mutants, and inductively coupled plasma mass spectroscopy, has enabled carefully controlled characterization of this novel innate immune antimicrobial pathway. In summary, our study provides new insights at the cellular level into the well-documented effects of zinc in promoting host defense against infectious disease, as well as the complex host subversion strategies employed by S Typhimurium to combat this pathway.-Kapetanovic, R., Bokil, N. J., Achard, M. E. S., Ong, C.-L. Y., Peters, K. M., Stocks, C. J., Phan, M.-D., Monteleone, M., Schroder, K., Irvine, K. M., Saunders, B. M., Walker, M. J., Stacey, K. J., McEwan, A. G., Schembri, M. A., Sweet, M. J. Salmonella employs multiple mechanisms to subvert the TLR-inducible zinc-mediated antimicrobial response of human macrophages. PMID- 26839377 TI - Brain penetration, target engagement, and disposition of the blood-brain barrier crossing bispecific antibody antagonist of metabotropic glutamate receptor type 1. AB - Receptor mediated transcytosis harnessing the cellular uptake and transport of natural ligands across the blood-brain barrier (BBB) has been identified as a means for antibody delivery to the CNS. In this study, we characterized bispecific antibodies in which a BBB-crossing antibody fragment FC5 was used as a BBB carrier. Cargo antibodies were either a high-affinity, selective antibody antagonist of the metabotropic glutamate receptor-1 (BBB-mGluR1), a widely abundant CNS target, or an IgG that does not bind the CNS target (BBB-NiP). Both BBB-NiP and BBB-mGluR1 demonstrated a similar 20-fold enhanced rate of transcytosis across an in vitro BBB model compared with mGluR1 IgG fused to a control antibody fragment. All 3 bispecific antibodies exhibited identical pharmacokinetics in vivo Comparative assessment of BBB-NiP and BBB-mGluR1 revealed that, whereas their serum pharmacokinetics and BBB penetration were identical, their central disposition (brain levels) and elimination (cerebrospinal fluid levels) were widely different, due to central target mediated removal of the mGluR1-engaging antibody. Central mGluR1 target engagement after systemic administration was demonstrated by a dose-dependent inhibition of mGluR-1-mediated thermal hyperalgesia and by colocalization of the antibody with thalamic neurons involved in mGluR1-mediated pain processing. We demonstrate the feasibility of targeting central G-protein-coupled receptors using a BBB-crossing bispecific antibody approach and emerging principles that govern brain distribution and disposition of these antibodies. These data will be important for designing safe and selective CNS antibody therapeutics.-Webster, C. I., Caram-Salas, N., Haqqani, A. S., Thom, G., Brown, L., Rennie, K., Yogi, A., Costain, W., Brunette, E., Stanimirovic, D. B. Brain penetration, target engagement, and disposition of the blood-brain barrier-crossing bispecific antibody antagonist of metabotropic glutamate receptor type 1. PMID- 26839378 TI - Disruption of nuclear factor (erythroid-derived-2)-like 2 antioxidant signaling: a mechanism for impaired activation of stem cells and delayed regeneration of skeletal muscle. AB - Recently we have reported that age-dependent decline in antioxidant levels accelerated apoptosis and skeletal muscle degeneration. Here, we demonstrate genetic ablation of the master cytoprotective transcription factor, nuclear factor (erythroid-derived-2)-like 2 (Nrf2), aggravates cardiotoxin (CTX)-induced tibialis anterior (TA) muscle damage. Disruption of Nrf2 signaling sustained the CTX-induced burden of reactive oxygen species together with compromised expression of antioxidant genes and proteins. Transcript/protein expression of phenotypic markers of muscle differentiation, namely paired box 7 (satellite cell) and early myogenic differentiation and terminal differentiation (myogenin and myosin heavy chain 2) were increased on d 2 and 4 postinjury but later returned to baseline levels on d 8 and 15 in wild-type (WT) mice. In contrast, these responses were persistently augmented in Nrf2-null mice suggesting that regulation of the regeneration-related signaling mechanisms require Nrf2 for normal functioning. Furthermore, Nrf2-null mice displayed slower regeneration marked by dysregulation of embryonic myosin heavy chain temporal expression. Histologic observations illustrated that Nrf2-null mice displayed smaller, immature TA muscle fibers compared with WT counterparts on d 15 after CTX injury. Improvement in TA muscle morphology and gain in muscle mass evident in the WT mice was not noticeable in the Nrf2-null animals. Taken together these data show that the satellite cell activation, proliferation, and differentiation requires a functional Nrf2 system for effective healing following injury.-Shelar, S. B., Narasimhan, M., Shanmugam, G., Litovsky, S. H., Gounder, S. S., Karan, G., Arulvasu, C., Kensler, T. W., Hoidal, J. R., Darley-Usmar, V. M., Rajasekaran, N. S. Disruption of nuclear factor (erythroid-derived-2)-like 2 antioxidant signaling: a mechanism for impaired activation of stem cells and delayed regeneration of skeletal muscle. PMID- 26839379 TI - A precursor-inducible zebrafish model of acute protoporphyria with hepatic protein aggregation and multiorganelle stress. AB - Protoporphyria is a metabolic disease that causes excess production of protoporphyrin IX (PP-IX), the final biosynthetic precursor to heme. Hepatic PP IX accumulation may lead to end-stage liver disease. We tested the hypothesis that systemic administration of porphyrin precursors to zebrafish larvae results in protoporphyrin accumulation and a reproducible nongenetic porphyria model. Retro-orbital infusion of PP-IX or the iron chelator deferoxamine mesylate (DFO), with the first committed heme precursor alpha-aminolevulinic acid (ALA), generates high levels of PP-IX in zebrafish larvae. Exogenously infused or endogenously produced PP-IX accumulates preferentially in the liver of zebrafish larvae and peaks 1 to 3 d after infusion. Similar to patients with protoporphyria, PP-IX is excreted through the biliary system. Porphyrin accumulation in zebrafish liver causes multiorganelle protein aggregation as determined by mass spectrometry and immunoblotting. Endoplasmic reticulum stress and induction of autophagy were noted in zebrafish larvae and corroborated in 2 mouse models of protoporphyria. Furthermore, electron microscopy of zebrafish livers from larvae administered ALA + DFO showed hepatocyte autophagosomes, nuclear membrane ruffling, and porphyrin-containing vacuoles with endoplasmic reticulum distortion. In conclusion, systemic administration of the heme precursors PP-IX or ALA + DFO into zebrafish larvae provides a new model of acute protoporphyria with consequent hepatocyte protein aggregation and proteotoxic multiorganelle alterations and stress.-Elenbaas, J. S., Maitra, D., Liu, Y., Lentz, S. I., Nelson, B., Hoenerhoff, M. J., Shavit, J. A., Omary, M. B. A precursor-inducible zebrafish model of acute protoporphyria with hepatic protein aggregation and multiorganelle stress. PMID- 26839381 TI - Potential pathogens, antimicrobial patterns and genotypic diversity of Escherichia coli isolates in constructed wetlands treating swine wastewater. AB - Escherichia coli populations originating from swine houses through constructed wetlands were analyzed for potential pathogens, antimicrobial susceptibility patterns, and genotypic diversity. Escherichia coli isolates (n = 493) were screened for the presence of the following virulence genes: stx1, stx2 and eae (Shiga toxin-producing E. coli [STEC]), heat-labile enterotoxin (LT) genes and heat stable toxin STa and STb (enterotoxigenic E. coli (ETEC), cytotoxin necrotizing factors 1 and 2 (cnf1 and cnf2 [necrotoxigenic E. coli- NTEC]), as well as O and H antigens, and the presence of the antibiotic resistance genes blaTEM, blaSHV, blaCMY-2, tet A, tet B, tet C, mph(A), aadA, StrA/B, sul1, sul2 and sul3. The commensal strains were further screened for 16 antimicrobials and characterized by BOX AIR-1 PCR for unique genotypes. The highest antibiotic resistance prevalence was for tetracycline, followed by erythromycin, ampicillin, streptomycin, sulfisoxazole and kanamycin. Our data showed that most of the isolates had high distribution of single or multidrug-resistant (MDR) genotypes. Therefore, the occurrence of MDR E. coli in the wetland is a matter of great concern due to possible transfer of resistance genes from nonpathogenic to pathogenic strains or vice versa in the environment. PMID- 26839380 TI - S-glutathiolation impairs phosphoregulation and function of cardiac myosin binding protein C in human heart failure. AB - Cardiac myosin-binding protein C (cMyBP-C) regulates actin-myosin interaction and thereby cardiac myocyte contraction and relaxation. This physiologic function is regulated by cMyBP-C phosphorylation. In our study, reduced site-specific cMyBP-C phosphorylation coincided with increased S-glutathiolation in ventricular tissue from patients with dilated or ischemic cardiomyopathy compared to nonfailing donors. We used redox proteomics, to identify constitutive and disease-specific S glutathiolation sites in cMyBP-C in donor and patient samples, respectively. Among those, a cysteine cluster in the vicinity of the regulatory phosphorylation sites within the myosin S2 interaction domain C1-M-C2 was identified and showed enhanced S-glutathiolation in patients. In vitro S-glutathiolation of recombinant cMyBP-C C1-M-C2 occurred predominantly at Cys(249), which attenuated phosphorylation by protein kinases. Exposure to glutathione disulfide induced cMyBP-C S-glutathiolation, which functionally decelerated the kinetics of Ca(2+) activated force development in ventricular myocytes from wild-type, but not those from Mybpc3-targeted knockout mice. These oxidation events abrogate protein kinase-mediated phosphorylation of cMyBP-C and therefore potentially contribute to the reduction of its phosphorylation and the contractile dysfunction observed in human heart failure.-Stathopoulou, K., Wittig, I., Heidler, J., Piasecki, A., Richter, F., Diering, S., van der Velden, J., Buck, F., Donzelli, S., Schroder, E., Wijnker, P. J. M., Voigt, N., Dobrev, D., Sadayappan, S., Eschenhagen, T., Carrier, L., Eaton, P., Cuello, F. S-glutathiolation impairs phosphoregulation and function of cardiac myosin-binding protein C in human heart failure. PMID- 26839382 TI - All the microbiology nematodes can teach us. AB - Be it their pervasiveness, experimental tractability or their impact on human health and agriculture, nematode-bacterium associations are far-reaching research subjects. Although the omics hype did not spare them and helped reveal mechanisms of communication and exchange between the associated partners, a huge amount of knowledge still awaits to be harvested from their study. Here, I summarize and compare the kind of research that has been already performed on the model nematode Caenorhabditis elegans and on symbiotic nematodes, both marine and entomopathogenic ones. The emerging picture highlights how complementing genetic studies with ecological ones (in the case of well-established genetic model systems such as C. elegans) and vice versa (in the case of the yet uncultured Stilbonematinae) will deepen our understanding of how microbial symbioses evolved and how they impact our environment. PMID- 26839384 TI - Editorial Commentary: 1, 2, 3 (Years) ... and You're Out: The End of a 123-year Historic Era. PMID- 26839385 TI - Correction to: "Prediction of the Clinical Risk of Drug-Induced Cholestatic Liver Injury Using an In Vitro Sandwich Cultured Hepatocyte Assay". PMID- 26839383 TI - Evaluation of Xpert MTB/RIF Versus AFB Smear and Culture to Identify Pulmonary Tuberculosis in Patients With Suspected Tuberculosis From Low and Higher Prevalence Settings. AB - BACKGROUND: The Xpert MTB/RIF (Xpert) assay is a rapid nucleic acid amplification test widely used in settings of high tuberculosis prevalence to detect tuberculosis as well asrpoBmutations associated with rifampin resistance. Data are needed on the diagnostic performance of Xpert in lower-prevalence settings to inform appropriate use for both tuberculosis detection and the need for respiratory isolation. METHODS: Xpert was compared to 2 sputum samples, each evaluated with acid-fast bacilli (AFB) smear and mycobacterial culture using liquid and solid culture media, from participants with suspected pulmonary tuberculosis from the United States, Brazil, and South Africa. RESULTS: Of 992 participants enrolled with evaluable results, 22% had culture-confirmed tuberculosis. In 638 (64%) US participants, 1 Xpert result demonstrated sensitivity of 85.2% (96.7% in participants with AFB smear-positive [AFB(+)] sputum, 59.3% with AFB smear-negative [AFB(-)] sputum), specificity of 99.2%, negative predictive value (NPV) of 97.6%, and positive predictive value of 94.9%. Results did not differ between higher- and low-prevalence settings. A second Xpert assay increased overall sensitivity to 91.1% (100% if AFB(+), 71.4% if AFB( )), with specificity of 98.9%. In US participants, a single negative Xpert result predicted the absence of AFB(+)/culture-positive tuberculosis with an NPV of 99.7%; NPV of 2 Xpert assays was 100%, suggesting a role in removing patients from airborne infection isolation. Xpert detected tuberculosis DNA and mutations associated with rifampin resistance in 5 of 7 participants with rifampin resistant, culture-positive tuberculosis. Specificity for rifampin resistance was 99.5% and NPV was 98.9%. CONCLUSIONS: In the United States, Xpert testing performed comparably to 2 higher-tuberculosis-prevalence settings. These data support the use of Xpert in the initial evaluation of tuberculosis suspects and in algorithms assessing need for respiratory isolation. PMID- 26839387 TI - Torsades de Pointes: 50 Years Later, Can We See It Coming? PMID- 26839386 TI - Prevalence of Microvolt T-Wave Alternans in Patients With Long QT Syndrome and Its Association With Torsade de Pointes. AB - BACKGROUND: Prevalence of microvolt T-wave alternans (TWA) and the strength of its association with torsade de pointes (TdP) history have not been fully investigated in patients with long QT syndrome (LQTS). METHODS AND RESULTS: Twenty-four-hour continuous 12-lead ECGs were recorded in 10 healthy subjects (5 men; median age, 21.5 years) and 32 patients (13 men; median age, 13 years) with LQTS types 1 (n=18), 2 (n=4), 3 (n=4), and unidentified (n=6). Peak TWA was determined by the Modified Moving Average method. None of the healthy subjects had TWA >=42 uV. All 8 (100%) LQTS patients with a history of TdP exhibited TWA >=42 uV, whereas only 14 (58.3%) of the 24 LQTS patients without TdP history reached >=42 uV (p=0.04). Thus, the 42-uV cut point provided 100% sensitivity and 41.7% specificity for an association with TdP history. In the 22 (68.8%) LQTS patients with TWA >=42 uV, only 2 (median; interquartile range, 1-3) leads exhibited TWA >=42 uV. Highest TWA levels were recorded in precordial leads (V1 V6) in 30 (93.8%) patients, most frequently in lead V2 (43.8%). A single ECG lead detected only <=63.6% of TWA >=42 uV episodes, whereas the combined leads V2 to V5 detected 100% of TWA >=42 uV. CONCLUSIONS: Microvolt TWA is far more prevalent in LQTS patients than previously reported and is strongly associated with TdP history. TWA should be monitored from precordial leads in LQTS patients. The use of a limited set of ECG leads in conventional monitoring has led to underestimation of TWA and its association with TdP. PMID- 26839388 TI - SPARC-Dependent Cardiomyopathy in Drosophila. AB - BACKGROUND: The Drosophila heart is an important model for studying the genetics underpinning mammalian cardiac function. The system comprises contractile cardiomyocytes, adjacent to which are pairs of highly endocytic pericardial nephrocytes that modulate cardiac function by uncharacterized mechanisms. Identifying these mechanisms and the molecules involved is important because they may be relevant to human cardiac physiology. METHODS AND RESULTS: This work aimed to identify circulating cardiomodulatory factors of potential relevance to humans using the Drosophila nephrocyte-cardiomyocyte system. A Kruppel-like factor 15 (dKlf15) loss-of-function strategy was used to ablate nephrocytes and then heart function and the hemolymph proteome were analyzed. Ablation of nephrocytes led to a severe cardiomyopathy characterized by a lengthening of diastolic interval. Rendering adult nephrocytes dysfunctional by disrupting their endocytic function or temporally conditional knockdown of dKlf15 led to a similar cardiomyopathy. Proteomics revealed that nephrocytes regulate the circulating levels of many secreted proteins, the most notable of which was the evolutionarily conserved matricellular protein Secreted Protein Acidic and Rich in Cysteine (SPARC), a protein involved in mammalian cardiac function. Finally, reducing SPARC gene dosage ameliorated the cardiomyopathy that developed in the absence of nephrocytes. CONCLUSIONS: The data implicate SPARC in the noncell autonomous control of cardiac function in Drosophila and suggest that modulation of SPARC gene expression may ameliorate cardiac dysfunction in humans. PMID- 26839390 TI - Acute Pulmonary Artery Embolism Detected by Noncontrast Functional Lung Magnetic Resonance Imaging. PMID- 26839389 TI - Assessing a peptidylic inhibitor-based therapeutic approach that simultaneously suppresses polyglutamine RNA- and protein-mediated toxicities in patient cells and Drosophila. AB - Polyglutamine (polyQ) diseases represent a group of progressive neurodegenerative disorders that are caused by abnormal expansion of CAG triplet nucleotides in disease genes. Recent evidence indicates that not only mutant polyQ proteins, but also their corresponding mutant RNAs, contribute to the pathogenesis of polyQ diseases. Here, we describe the identification of a 13-amino-acid peptide, P3, which binds directly and preferentially to long-CAG RNA within the pathogenic range. When administered to cell and Drosophila disease models, as well as to patient-derived fibroblasts, P3 inhibited expanded-CAG-RNA-induced nucleolar stress and suppressed neurotoxicity. We further examined the combined therapeutic effect of P3 and polyQ-binding peptide 1 (QBP1), a well-characterized polyQ protein toxicity inhibitor, on neurodegeneration. When P3 and QBP1 were co administered to disease models, both RNA and protein toxicities were effectively mitigated, resulting in a notable improvement of neurotoxicity suppression compared with the P3 and QBP1 single-treatment controls. Our findings indicate that targeting toxic RNAs and/or simultaneous targeting of toxic RNAs and their corresponding proteins could open up a new therapeutic strategy for treating polyQ degeneration. PMID- 26839392 TI - The Rotterdam Radial Access Research: Ultrasound-Based Radial Artery Evaluation for Diagnostic and Therapeutic Coronary Procedures. AB - BACKGROUND: Radial artery wall might be damaged after cannulation for cardiac catheterization. We investigated structural changes of the radial artery wall after catheterization to understand whether these might predict radial pulsation loss or occlusion and local pain or functional impairment of the upper extremity. METHODS AND RESULTS: Ninety patients underwent transradial coronary angiography or intervention and were scanned with a high-resolution 40-MHz ultrasound before cannulation and at 3 hours and 30 days after procedure. Acute injuries of the radial artery occurred in all patients: dissection and intramural hematoma were the most common. However, these phenomena did not predict loss of radial pulsation or occlusion, local pain, or functional impairment at 30 days. Overall, the radial artery lumen was significantly reduced distal to the puncture site. Radial artery intima and total wall thickness increased 3 hours after puncture and persisted at 30 days. Radial occlusion and pulsation loss were observed in 3.9% and 9.2% of patients, respectively, at 30 days. Smaller radial artery lumen at baseline increased the risk of radial pulsation loss at 30 days (odds ratio, 1.23; P=0.049). The number of radial puncture attempts predicted pulsation loss (odds ratio, 2.64; P=0.027), occlusion (odds ratio, 3.49; P=0.022), and symptoms (odds ratio, 2.24; P=0.05) at 30-day follow-up. CONCLUSIONS: After catheterization, radial artery puncture site is associated with increased intima and total wall thickness and with modest decrease of inner lumen diameter. Acute injuries of the vessel wall were ubiquitous, but contrary to repeated puncture attempts, did not seem to affect postprocedural radial occlusion or loss of pulsation. PMID- 26839391 TI - Femoropopliteal Artery Stent Thrombosis: Report From the Excellence in Peripheral Artery Disease Registry. AB - BACKGROUND: There are limited data on femoropopliteal artery stent thrombosis (ST), which is a serious adverse outcome of peripheral artery interventions. METHODS AND RESULTS: Index procedures resulting in femoropopliteal ST were compared with stent procedures without subsequent ST in the Excellence in Peripheral Artery Disease registry. The study data had a total of 724 cases of stent procedures and 604 unique patients. Femoropopliteal ST occurred in 26 of 604 patients (4.3%) over a median follow-up of 6 months post procedure. ST was more likely to occur in men (96.3% versus 82.2%; P=0.026) and to have an initial intervention for chronic total occlusions (88.5% versus 64.0%; P=0.01). There was no significant difference in ST between drug-coated and bare-metal stents (4.4% versus 3.4%; P=0.55), but the rate of ST was significantly higher with self expanding covered stent grafts compared with bare-metal stents (10.6% versus 3.4%; P=0.02). ST was significantly associated with an increased risk of 12-month major adverse limb events (hazard ratio, 4.99; 95% confidence interval, 2.31 10.77; P<0.001) compared with no ST. On multivariate analysis, treatment of chronic total occlusion lesions (odds ratio, 3.46; 95% confidence interval, 0.98 12.20; P=0.05) and in-stent restenosis lesions (odds ratio, 5.30; 95% confidence interval, 1.83-15.32; P=0.002) were independently associated with an increased risk of ST. CONCLUSIONS: In a multicenter peripheral interventional registry, femoropopliteal ST occurred in 4.3% of patients who underwent stent procedures, and it was associated with treatment of chronic total occlusions and in-stent restenosis lesions, and had higher 12-month major adverse limb events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01904851. PMID- 26839393 TI - Vascular Healing of a False Lumen After Bioresorbable Scaffold Implantation. PMID- 26839394 TI - Chronic Therapy With Elamipretide (MTP-131), a Novel Mitochondria-Targeting Peptide, Improves Left Ventricular and Mitochondrial Function in Dogs With Advanced Heart Failure. AB - BACKGROUND: Elamipretide (MTP-131), a novel mitochondria-targeting peptide, was shown to reduce infarct size in animals with myocardial infarction and improve renal function in pigs with acute and chronic kidney injury. This study examined the effects of chronic therapy with elamipretide on left ventricular (LV) and mitochondrial function in dogs with heart failure (HF). METHODS AND RESULTS: Fourteen dogs with microembolization-induced HF were randomized to 3 months monotherapy with subcutaneous injections of elamipretide (0.5 mg/kg once daily, HF+ELA, n=7) or saline (control, HF-CON, n=7). LV ejection fraction, plasma n terminal pro-brain natriuretic peptide, tumor necrosis factor-alpha, and C reactive protein were measured before (pretreatment) and 3 months after initiating therapy (post-treatment). Mitochondrial respiration, membrane potential (Deltapsim), maximum rate of ATP synthesis, and ATP/ADP ratio were measured in isolated LV cardiomyocytes obtained at post-treatment. In HF-CON dogs, ejection fraction decreased at post-treatment compared with pretreatment (29 +/- 1% versus 31 +/- 2%), whereas in HF+ELA dogs, ejection fraction significantly increased at post-treatment compared with pretreatment (36 +/- 2% versus 30 +/- 2%; P<0.05). In HF-CON, n-terminal pro-brain natriuretic peptide increased by 88 +/- 120 pg/mL during follow-up but decreased significantly by 774 +/- 85 pg/mL in HF+ELA dogs (P<0.001). Treatment with elamipretide also normalized plasma tumor necrosis factor-alpha and C-reactive protein and restored mitochondrial state-3 respiration, Deltapsim, rate of ATP synthesis, and ATP/ADP ratio (ATP/ADP: 0.38 +/- 0.04 HF-CON versus 1.16 +/- 0.15 HF+ELA; P<0.001). CONCLUSIONS: Long-term therapy with elamipretide improves LV systolic function, normalizes plasma biomarkers, and reverses mitochondrial abnormalities in LV myocardium of dogs with advanced HF. The results support the development of elamipretide for the treatment of HF. PMID- 26839397 TI - Using the mouse to model human disease: increasing validity and reproducibility. AB - Experiments that use the mouse as a model for disease have recently come under scrutiny because of the repeated failure of data, particularly derived from preclinical studies, to be replicated or translated to humans. The usefulness of mouse models has been questioned because of irreproducibility and poor recapitulation of human conditions. Newer studies, however, point to bias in reporting results and improper data analysis as key factors that limit reproducibility and validity of preclinical mouse research. Inaccurate and incomplete descriptions of experimental conditions also contribute. Here, we provide guidance on best practice in mouse experimentation, focusing on appropriate selection and validation of the model, sources of variation and their influence on phenotypic outcomes, minimum requirements for control sets, and the importance of rigorous statistics. Our goal is to raise the standards in mouse disease modeling to enhance reproducibility, reliability and clinical translation of findings. PMID- 26839395 TI - Cancer Therapy-Related Cardiac Dysfunction and Heart Failure: Part 2: Prevention, Treatment, Guidelines, and Future Directions. AB - Success with oncologic treatment has allowed cancer patients to experience longer cancer-free survival gains. Unfortunately, this success has been tempered by unintended and often devastating cardiac complications affecting overall patient outcomes. Cardiac toxicity, specifically the association of several cancer therapy agents with the development of left ventricular dysfunction and cardiomyopathy, is an issue of growing concern. Although the pathophysiologic mechanisms behind cardiac toxicity have been characterized, there is currently no evidence-based approach for monitoring and management of these patients. In the first of a 2-part review, we discuss the epidemiologic, pathophysiologic, risk factors, and imaging aspects of cancer therapy-related cardiac dysfunction and heart failure. In this second part, we discuss the prevention and treatment aspects in these patients and conclude with highlighting the evidence gaps and future directions for research in this area. PMID- 26839398 TI - Echoes of the embryo: using the developmental biology toolkit to study cancer. AB - The hallmark of embryonic development is regulation - the tendency for cells to find their way into organized and 'well behaved' structures - whereas cancer is characterized by dysregulation and disorder. At face value, cancer biology and developmental biology would thus seem to have little to do with each other. But if one looks beneath the surface, embryos and cancers share a number of cellular and molecular features. Embryos arise from a single cell and undergo rapid growth involving cell migration and cell-cell interactions: features that are also seen in the context of cancer. Consequently, many of the experimental tools that have been used to study embryogenesis for over a century are well-suited to studying cancer. This article will review the similarities between embryogenesis and cancer progression and discuss how some of the concepts and techniques used to understand embryos are now being adapted to provide insight into tumorigenesis, from the origins of cancer cells to metastasis. PMID- 26839401 TI - Light to moderate alcohol intake may be associated with non-minimal cancer risk. PMID- 26839400 TI - ER stress and basement membrane defects combine to cause glomerular and tubular renal disease resulting from Col4a1 mutations in mice. AB - Collagen IV is a major component of basement membranes, and mutations in COL4A1, which encodes collagen IV alpha chain 1, cause a multisystemic disease encompassing cerebrovascular, eye and kidney defects. However, COL4A1 renal disease remains poorly characterized and its pathomolecular mechanisms are unknown. We show that Col4a1 mutations in mice cause hypotension and renal disease, including proteinuria and defects in Bowman's capsule and the glomerular basement membrane, indicating a role for Col4a1 in glomerular filtration. Impaired sodium reabsorption in the loop of Henle and distal nephron despite elevated aldosterone levels indicates that tubular defects contribute to the hypotension, highlighting a novel role for the basement membrane in vascular homeostasis by modulation of the tubular response to aldosterone. Col4a1 mutations also cause diabetes insipidus, whereby the tubular defects lead to polyuria associated with medullary atrophy and a subsequent reduction in the ability to upregulate aquaporin 2 and concentrate urine. Moreover, haematuria, haemorrhage and vascular basement membrane defects confirm an important vascular component. Interestingly, although structural and compositional basement membrane defects occurred in the glomerulus and Bowman's capsule, no tubular basement membrane defects were detected. By contrast, medullary atrophy was associated with chronic ER stress, providing evidence for cell-type-dependent molecular mechanisms of Col4a1 mutations. These data show that both basement membrane defects and ER stress contribute to Col4a1 renal disease, which has important implications for the development of treatment strategies for collagenopathies. PMID- 26839402 TI - Early exposure to dogs and farm animals reduces risk of childhood asthma. PMID- 26839403 TI - Filtered sunlight reduces serum bilirubin levels as effectively as conventional phototherapy in late preterm and term neonates with mild jaundice. PMID- 26839404 TI - Building accelerator afterburners with plasma. PMID- 26839399 TI - The short-lived African turquoise killifish: an emerging experimental model for ageing. AB - Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model. PMID- 26839406 TI - Induction of de novo alpha-synuclein fibrillization in a neuronal model for Parkinson's disease. AB - Lewy bodies (LBs) are intraneuronal inclusions consisting primarily of fibrillized human alpha-synuclein (halpha-Syn) protein, which represent the major pathological hallmark of Parkinson's disease (PD). Although doubling halpha-Syn expression provokes LB pathology in humans, halpha-Syn overexpression does not trigger the formation of fibrillar LB-like inclusions in mice. We hypothesized that interactions between exogenous halpha-Syn and endogenous mouse synuclein homologs could be attenuating halpha-Syn fibrillization in mice, and therefore, we systematically assessed halpha-Syn aggregation propensity in neurons derived from alpha-Syn-KO, beta-Syn-KO, gamma-Syn-KO, and triple-KO mice lacking expression of all three synuclein homologs. Herein, we show that halpha-Syn forms hyperphosphorylated (at S129) and ubiquitin-positive LB-like inclusions in primary neurons of alpha-Syn-KO, beta-Syn-KO, and triple-KO mice, as well as in transgenic alpha-Syn-KO mouse brains in vivo. Importantly, correlative light and electron microscopy, immunogold labeling, and thioflavin-S binding established their fibrillar ultrastructure, and fluorescence recovery after photobleaching/photoconversion experiments showed that these inclusions grow in size and incorporate soluble proteins. We further investigated whether the presence of homologous alpha-Syn species would interfere with the seeding and spreading of alpha-Syn pathology. Our results are in line with increasing evidence demonstrating that the spreading of alpha-Syn pathology is most prominent when the injected preformed fibrils and host-expressed alpha-Syn monomers are from the same species. These findings provide insights that will help advance the development of neuronal and in vivo models for understanding mechanisms underlying halpha-Syn intraneuronal fibrillization and its contribution to PD pathogenesis, and for screening pharmacologic and genetic modulators of alpha-Syn fibrillization in neurons. PMID- 26839408 TI - Differential vesicular sorting of AMPA and GABAA receptors. AB - In mature neurons AMPA receptors cluster at excitatory synapses primarily on dendritic spines, whereas GABAA receptors cluster at inhibitory synapses mainly on the soma and dendritic shafts. The molecular mechanisms underlying the precise sorting of these receptors remain unclear. By directly studying the constitutive exocytic vesicles of AMPA and GABAA receptors in vitro and in vivo, we demonstrate that they are initially sorted into different vesicles in the Golgi apparatus and inserted into distinct domains of the plasma membrane. These insertions are dependent on distinct Rab GTPases and SNARE complexes. The insertion of AMPA receptors requires SNAP25-syntaxin1A/B-VAMP2 complexes, whereas insertion of GABAA receptors relies on SNAP23-syntaxin1A/B-VAMP2 complexes. These SNARE complexes affect surface targeting of AMPA or GABAA receptors and synaptic transmission. Our studies reveal vesicular sorting mechanisms controlling the constitutive exocytosis of AMPA and GABAA receptors, which are critical for the regulation of excitatory and inhibitory responses in neurons. PMID- 26839407 TI - Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release. AB - A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications. PMID- 26839409 TI - Axons provide the secretory machinery for trafficking of voltage-gated sodium channels in peripheral nerve. AB - The regulation of the axonal proteome is key to generate and maintain neural function. Fast and slow axoplasmic waves have been known for decades, but alternative mechanisms to control the abundance of axonal proteins based on local synthesis have also been identified. The presence of the endoplasmic reticulum has been documented in peripheral axons, but it is still unknown whether this localized organelle participates in the delivery of axonal membrane proteins. Voltage-gated sodium channels are responsible for action potentials and are mostly concentrated in the axon initial segment and nodes of Ranvier. Despite their fundamental role, little is known about the intracellular trafficking mechanisms that govern their availability in mature axons. Here we describe the secretory machinery in axons and its contribution to plasma membrane delivery of sodium channels. The distribution of axonal secretory components was evaluated in axons of the sciatic nerve and in spinal nerve axons after in vivo electroporation. Intracellular protein trafficking was pharmacologically blocked in vivo and in vitro. Axonal voltage-gated sodium channel mRNA and local trafficking were examined by RT-PCR and a retention-release methodology. We demonstrate that mature axons contain components of the endoplasmic reticulum and other biosynthetic organelles. Axonal organelles and sodium channel localization are sensitive to local blockade of the endoplasmic reticulum to Golgi transport. More importantly, secretory organelles are capable of delivering sodium channels to the plasma membrane in isolated axons, demonstrating an intrinsic capacity of the axonal biosynthetic route in regulating the axonal proteome in mammalian axons. PMID- 26839410 TI - Spatial structure of neuronal receptive field in awake monkey secondary visual cortex (V2). AB - Visual processing depends critically on the receptive field (RF) properties of visual neurons. However, comprehensive characterization of RFs beyond the primary visual cortex (V1) remains a challenge. Here we report fine RF structures in secondary visual cortex (V2) of awake macaque monkeys, identified through a projection pursuit regression analysis of neuronal responses to natural images. We found that V2 RFs could be broadly classified as V1-like (typical Gabor-shaped subunits), ultralong (subunits with high aspect ratios), or complex-shaped (subunits with multiple oriented components). Furthermore, single-unit recordings from functional domains identified by intrinsic optical imaging showed that neurons with ultralong RFs were primarily localized within pale stripes, whereas neurons with complex-shaped RFs were more concentrated in thin stripes. Thus, by combining single-unit recording with optical imaging and a computational approach, we identified RF subunits underlying spatial feature selectivity of V2 neurons and demonstrated the functional organization of these RF properties. PMID- 26839411 TI - Strand-biased cytosine deamination at the replication fork causes cytosine to thymine mutations in Escherichia coli. AB - The rate of cytosine deamination is much higher in single-stranded DNA (ssDNA) than in double-stranded DNA, and copying the resulting uracils causes C to T mutations. To study this phenomenon, the catalytic domain of APOBEC3G (A3G-CTD), an ssDNA-specific cytosine deaminase, was expressed in an Escherichia coli strain defective in uracil repair (ung mutant), and the mutations that accumulated over thousands of generations were determined by whole-genome sequencing. C:G to T:A transitions dominated, with significantly more cytosines mutated to thymine in the lagging-strand template (LGST) than in the leading-strand template (LDST). This strand bias was present in both repair-defective and repair-proficient cells and was strongest and highly significant in cells expressing A3G-CTD. These results show that the LGST is accessible to cellular cytosine deaminating agents, explains the well-known GC skew in microbial genomes, and suggests the APOBEC3 family of mutators may target the LGST in the human genome. PMID- 26839412 TI - Hybrid promiscuous (Hypr) GGDEF enzymes produce cyclic AMP-GMP (3', 3'-cGAMP). AB - Over 30 years ago, GGDEF domain-containing enzymes were shown to be diguanylate cyclases that produce cyclic di-GMP (cdiG), a second messenger that modulates the key bacterial lifestyle transition from a motile to sessile biofilm-forming state. Since then, the ubiquity of genes encoding GGDEF proteins in bacterial genomes has established the dominance of cdiG signaling in bacteria. However, the observation that proteobacteria encode a large number of GGDEF proteins, nearing 1% of coding sequences in some cases, raises the question of why bacteria need so many GGDEF enzymes. In this study, we reveal that a subfamily of GGDEF enzymes synthesizes the asymmetric signaling molecule cyclic AMP-GMP (cAG or 3', 3' cGAMP). This discovery is unexpected because GGDEF enzymes function as symmetric homodimers, with each monomer binding to one substrate NTP. Detailed analysis of the enzyme from Geobacter sulfurreducens showed it is a dinucleotide cyclase capable of switching the major cyclic dinucleotide (CDN) produced based on ATP-to GTP ratios. We then establish through bioinformatics and activity assays that hybrid CDN-producing and promiscuous substrate-binding (Hypr) GGDEF enzymes are found in other deltaproteobacteria. Finally, we validated the predictive power of our analysis by showing that cAG is present in surface-grown Myxococcus xanthus. This study reveals that GGDEF enzymes make alternative cyclic dinucleotides to cdiG and expands the role of this widely distributed enzyme family to include regulation of cAG signaling. PMID- 26839414 TI - Interleukin-10 neutralizing antibody for detection of intestinal luminal levels and as a dietary additive in Eimeria challenged broiler chicks. AB - Interleukin-10 (IL-10) mRNA levels are increased within intestinal mucosa after Eimeria infection. IL-10 apical receptor presence on enterocytes suggests IL-10 is secreted into the intestinal lumen. Increased IL-10 has been shown to be central to the pathogenesis of numerous intracellular pathogens; we hypothesize luminal secretion of IL-10 enables Eimeria spp. infection in chickens. This study examines intestine luminal IL-10 levels and performance in broilers challenged with Eimeria when fed an anti-IL-10 antibody. Chicks were fed a diet (1 to 21 d) with control or anti-IL-10 antibody (0.34 g egg yolk antibody powder/Kg diet) with a saline or 10* dose of Advent coccidiosis vaccine on d 3. One chick per pen was euthanized on days 2, 4, 7, 10, 13, 16, and 19 post-challenge, bled, and intestines were collected for luminal fluid IL-10 concentrations. Body weight and feed intake were measured on d 21, and oocyst shedding was assessed on d 7 post challenge. A significant Eimeria * antibody interaction on d 21 body weight (P < 0.05) showed chicks fed control antibody, but not anti-IL-10, had significant reductions in body weight when challenged with Eimeria spp. Oocyst shedding was increased with Eimeria challenge, but dietary antibody had no effect. Plasma carotenoid levels were reduced in Eimeria challenged chicks 4, 7, 10, and 16 days post-challenge compared to unchallenged chicks. Lack of an Eimeria * antibody interaction showed anti-IL-10 was not protective against Eimeria-induced decreases in plasma carotenoids. Eimeria challenge increased intestine luminal IL 10 on days 4 and 7 post-challenge in the cecum and jejunum, respectively, compared to unchallenged. Dietary anti-IL-10 decreased luminal IL-10 in the ileum on day 2 post-challenge when compared to control antibody fed chicks. No interaction between Eimeria challenge and antibody was observed on intestine luminal contents of IL-10, suggesting anti-IL-10 was ineffective at preventing increased Eimeria-induced luminal IL-10. In conclusion, Eimeria challenge increased intestinal luminal IL-10 and anti-IL-10 was effective at preventing Eimeria-induced decreased body weight, however the mechanism anti-IL-10 antibody protects body weight during Eimeria challenge remains unknown. PMID- 26839413 TI - alpha-Synuclein-induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models. AB - Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the accumulation of protein aggregates comprised of alpha synuclein (alpha-syn). A major barrier in treatment discovery for PD is the lack of identifiable therapeutic pathways capable of reducing aggregates in human neuronal model systems. Mutations in key components of protein trafficking and cellular degradation machinery represent important risk factors for PD; however, their precise role in disease progression and interaction with alpha-syn remains unclear. Here, we find that alpha-syn accumulation reduced lysosomal degradation capacity in human midbrain dopamine models of synucleinopathies through disrupting hydrolase trafficking. Accumulation of alpha-syn at the cell body resulted in aberrant association with cis-Golgi-tethering factor GM130 and disrupted the endoplasmic reticulum-Golgi localization of rab1a, a key mediator of vesicular transport. Overexpression of rab1a restored Golgi structure, improved hydrolase trafficking and activity, and reduced pathological alpha-syn in patient neurons. Our work suggests that enhancement of lysosomal hydrolase trafficking may prove beneficial in synucleinopathies and indicates that human midbrain disease models may be useful for identifying critical therapeutic pathways in PD and related disorders. PMID- 26839415 TI - Genetic variation of major histocompatibility complex (MHC) in wild Red Junglefowl (Gallus gallus). AB - The major histocompatibility complex (MHC) is a multi-family gene cluster that encodes proteins with immuno-responsive function. While studies of MHC in domesticated poultry are relatively common, very little is known about this highly polymorphic locus in wild Red Junglefowl (Gallus gallus), the natural progenitor of domestic chickens. We investigated the diversity of MHC within and among four wild Red Junglefowl populations across diversified natural habitats in South Central Vietnam. Based on a SNP panel of 84 sites spanning 210 Kb of the MHC-B locus, we identified 310 unique haplotypes in 398 chromosomes. None of these haplotypes have been described before and we did not observe any of the wild Red Junglefowl haplotypes in domesticated chickens. Analysis of molecular variance (AMOVA) revealed that 94.51% of observed haplotype variation was accounted for at the within individual level. Little genetic variance was apportioned within and among populations, the latter accounting only for 0.83%. We also found evidence of increased recombination, including numerous hotspots, and limited linkage disequilibrium among the 84 SNP sites. Compared to an average haplotype diversity of 3.55% among seventeen lines of domestic chickens, our results suggest extraordinarily high haplotype diversity remains in wild Red Junglefowl and is consistent with a pattern of balancing selection. Wild Red Junglefowl in Vietnam, therefore, represent a rich resource of natural genomic variation independent from artificial selection. PMID- 26839417 TI - Acetylcholinesterase immobilization and characterization, and comparison of the activity of the porous silicon-immobilized enzyme with its free counterpart. AB - A successful prescription is presented for acetylcholinesterase physically adsorbed on to a mesoporous silicon surface, with a promising hydrolytic response towards acetylthiocholine iodide. The catalytic behaviour of the immobilized enzyme was assessed by spectrophotometric bioassay using neostigmine methyl sulfate as a standard acetycholinesterase inhibitor. The surface modification was studied through field emission SEM, Fourier transform IR spectroscopy, energy dispersive X-ray spectroscopy, cathode luminescence and X-ray photoelectron spectroscopy analysis, photoluminescence measurement and spectrophotometric bioassay. The porous silicon-immobilized enzyme not only yielded greater enzyme stability, but also significantly improved the native photoluminescence at room temperature of the bare porous silicon architecture. The results indicated the promising catalytic behaviour of immobilized enzyme compared with that of its free counterpart, with a greater stability, and that it aided reusability and easy separation from the reaction mixture. The porous silicon-immobilized enzyme was found to retain 50% of its activity, promising thermal stability up to 90 degrees C, reusability for up to three cycles, pH stability over a broad pH of 4 9 and a shelf-life of 44 days, with an optimal hydrolytic response towards acetylthiocholine iodide at variable drug concentrations. On the basis of these findings, it was believed that the porous silicon-immobilized enzyme could be exploited as a reusable biocatalyst and for screening of acetylcholinesterase inhibitors from crude plant extracts and synthesized organic compounds. Moreover, the immobilized enzyme could offer a great deal as a viable biocatalyst in bioprocessing for the chemical and pharmaceutical industries, and bioremediation to enhance productivity and robustness. PMID- 26839419 TI - A Reflection of Faculty and Course Evaluations. PMID- 26839418 TI - Latrunculin B modulates electrophysiological characteristics and arrhythmogenesis in pulmonary vein cardiomyocytes. AB - AF (atrial fibrillation) is the most common sustained arrhythmia, and the PVs (pulmonary veins) play a critical role in triggering AF. Stretch causes structural remodelling, including cytoskeleton rearrangement, which may play a role in the genesis of AF. Lat-B (latrunculin B), an inhibitor of actin polymerization, is involved in Ca(2+) regulation. However, it is unclear whether Lat-B directly modulates the electrophysiological characteristics and Ca(2+) homoeostasis of the PVs. Conventional microelectrodes, whole-cell patch-clamp, and the fluo-3 fluorimetric ratio technique were used to record ionic currents and intracellular Ca(2+) within isolated rabbit PV preparations, or within isolated single PV cardiomyocytes, before and after administration of Lat-B (100 nM). Langendorff-perfused rabbit hearts were exposed to acute and continuous atrial stretch, and we studied PV electrical activity. Lat-B (100 nM) decreased the spontaneous electrical activity by 16+/-4% in PV preparations. Lat-B (100 nM) decreased the late Na(+) current, L-type Ca(2+) current, Na(+)/Ca(2+) exchanger current, and stretch-activated BKCa current, but did not affect the Na(+) current in PV cardiomyocytes. Lat-B reduced the transient outward K(+) current and ultra rapid delayed rectifier K(+) current, but increased the delayed rectifier K(+) current in isolated PV cardiomyocytes. In addition, Lat-B (100 nM) decreased intracellular Ca(2+) transient and sarcoplasmic reticulum Ca(2+) content in PV cardiomyocytes. Moreover, Lat-B attenuated stretch-induced increased spontaneous electrical activity and trigger activity. The effects of Lat-B on the PV spontaneous electrical activity were attenuated in the presence of Y-27632 [10 MUM, a ROCK (Rho-associated kinase) inhibitor] and cytochalasin D (10 MUM, an actin polymerization inhibitor). In conclusion, Lat-B regulates PV electrophysiological characteristics and attenuates stretch-induced arrhythmogenesis. PMID- 26839416 TI - Combined defects in oxidative phosphorylation and fatty acid beta-oxidation in mitochondrial disease. AB - Mitochondria provide the main source of energy to eukaryotic cells, oxidizing fats and sugars to generate ATP. Mitochondrial fatty acid beta-oxidation (FAO) and oxidative phosphorylation (OXPHOS) are two metabolic pathways which are central to this process. Defects in these pathways can result in diseases of the brain, skeletal muscle, heart and liver, affecting approximately 1 in 5000 live births. There are no effective therapies for these disorders, with quality of life severely reduced for most patients. The pathology underlying many aspects of these diseases is not well understood; for example, it is not clear why some patients with primary FAO deficiencies exhibit secondary OXPHOS defects. However, recent findings suggest that physical interactions exist between FAO and OXPHOS proteins, and that these interactions are critical for both FAO and OXPHOS function. Here, we review our current understanding of the interactions between FAO and OXPHOS proteins and how defects in these two metabolic pathways contribute to mitochondrial disease pathogenesis. PMID- 26839420 TI - Disruptive Innovations Addressing Quality, Access, and Cost Alternatives for Faculty Development. PMID- 26839421 TI - An Industrial Engineering Approach to Cost Containment of Pharmacy Education. AB - A 2-semester project explored employing teams of fourth-year industrial engineering students to optimize some of our academic management processes. Results included significant cost savings and increases in efficiency, effectiveness, and student and faculty satisfaction. While we did not adopt all of the students' recommendations, we did learn some important lessons. For example, an initial investment of time in developing a mutually clear understanding of the problems, constraints, and goals maximizes the value of industrial engineering analysis and recommendations. Overall, industrial engineering was a valuable tool for optimizing certain academic management processes. PMID- 26839422 TI - A Student-Led Health Education Initiative Addressing Health Disparities in a Chinatown Community. AB - Together with community advocates, professional student organizations can help improve access to health care and sustain services to address the health disparities of a community in need. This paper examines the health concerns of an underserved Chinese community and introduces a student-led health education initiative that fosters service learning and student leadership. The initiative was recognized by the American Association of Colleges of Pharmacy (AACP) and received the 2012-2013 Student Community Engaged Service Award. PMID- 26839423 TI - A Chronic Disease State Simulation in an Ambulatory Care Elective Course. AB - OBJECTIVE: To implement a chronic disease state simulation in an ambulatory care elective course and to assess the simulation's impact on students' perceptions of their empathy toward patients and of their counseling skills. DESIGN: The chronic disease state simulation occurred over 2 weeks. Students alternated playing the role of patient and pharmacist. As patients, students adhered to medication regimens, lifestyle modifications, and blood glucose or blood pressure monitoring. As pharmacists, students conducted patient interviews, and provided education and counseling. Empathy and counseling skills were assessed through course surveys, written reflections, and SOAP notes. ASSESSMENT: Results from a cohort of 130 students indicated the simulation enhanced students' perceptions of their abilities to empathize with and counsel patients with chronic diseases. CONCLUSION: The chronic disease state simulation provides a novel approach to develop skills needed for working with complex patient cases in ambulatory care settings. PMID- 26839424 TI - Pharmacy Student and Preceptor Impressions of Faculty Liaison Visits to Experiential Training Sites. AB - OBJECTIVE: To characterize preceptor and student views about and experiences with faculty liaison visits to practice sites during clinical internships. METHODS: A survey was administered at the conclusion of each of the first 3 academic years of a new postbaccalaureate doctor of pharmacy (PharmD) program. RESULTS: Preceptors were satisfied overall with faculty liaison visits, while students initially were not; however, their perception increased in subsequent years. Students felt development of their patient care skills benefited, but less so their interpersonal communication skills. Each year, almost all preceptors indicated faculty liaison visits were helpful in developing and refining their mentorship skills. CONCLUSION: Faculty liaison visits provided a valuable opportunity to interact and support preceptors and students during advanced pharmacy internships in a nascent PharmD program. PMID- 26839425 TI - Perceptions and Cost-Analysis of a Multiple Mini-Interview in a Pharmacy School Admissions Process. AB - OBJECTIVE: To improve the quality of admissions interviews for a doctor of pharmacy program, using a multiple mini-interview (MMI) in place of the standard interview. METHODS: Stakeholders completed an anonymous web-based survey. This study characterized perceptions of the MMI format across 3 major stakeholders (candidates, interviewers, admissions committee members) and included comparative cost estimates.Costs were estimated using human and facility resources from the 2012 cycle (standard format) and the 2013 cycle (MMI format). RESULTS: Most candidates (65%), interviewers (86%), and admissions committee members (79%) perceived the MMI format as effective for evaluating applicants, and most (59% of candidates, 84% of interviewers, 77% of committee members) agreed that the MMI format should be continued. Cost per candidate interviewed was $136.34 (standard interview) vs $75.30 (MMI). CONCLUSION: Perceptions of the MMI process were favorable across stakeholder groups, and this format was less costly per candidate interviewed. PMID- 26839426 TI - Publication Rates for Pharmaceutical Sciences Faculty Members at Nonresearch Intensive US Schools of Pharmacy. AB - OBJECTIVE: To provide benchmarking data for faculty productivity by determining publication rates for pharmaceutical sciences faculty members at nonresearch intensive schools and colleges of pharmacy between January 2010 and December 2013. METHODS: Scopus and Web of Science databases were searched using faculty names from the AACP faculty and professional staff roster. Annual publication rates were calculated and compared for various demographic subcategories. RESULTS: The average annual publication rate for the 4-year period was 0.82 per faculty member, and 10.95 per institution. Publication rates were significantly higher in departments offering a PhD program or with NIH funding. CONCLUSION: Because institutional missions are diverse, it can be useful to evaluate faculty scholarly productivity in relation to similar organizations. Pharmaceutical science faculty members at nonresearch-intensive institutions contribute to the literature despite institutional missions less focused on research. PMID- 26839427 TI - Implementation and Use of the Pharmacy Curriculum Outcomes Assessment at US Schools of Pharmacy. AB - OBJECTIVE: To describe how schools and colleges of pharmacy use the Pharmacy Curriculum Outcomes Assessment (PCOA) in relation to student assessment and curricular feedback. METHODS: A survey was distributed to all programs that have implemented the PCOA. The survey was designed to assess 3 domains regarding the use of the PCOA: rationale for use, logistics of administration, and performance data review and distribution. RESULTS: A 79% response rate (41/52) was obtained. The mix of responses was 93% current PCOA users and 7% past users. The most common reasons for PCOA use were for programmatic assessment and benchmarking. The examination was most frequently administered during the P3 year, with minimal stakes attached to performance. Significant differences in responses based on public vs private institution were seen with respect to length of accreditation of current PCOA users, messaging to students regarding performance, inclusion of results in student advising, and distribution of results to stakeholders. CONCLUSION: Programs were using the PCOA primarily as an assessment in the P3 year for reasons related to programmatic and curricular assessment. Some differences existed between public and private institutional PCOA use and examination-related processes and results distribution. PMID- 26839428 TI - Early Clinical Experiences for Second-Year Student Pharmacists at an Academic Medical Center. AB - OBJECTIVE: To examine student outcomes associated with the Student Medication and Reconciliation Team (SMART) program, which was designed to provide second-year student pharmacists at the University of North Carolina (UNC) Eshelman School of Pharmacy direct patient care experience at UNC Medical Center. DESIGN: Twenty-two second-year student pharmacists were randomly selected from volunteers, given program training, and scheduled for three 5-hour evening shifts in 2013-2014. Pre/post surveys and reflection statements were collected from 19 students. Data were analyzed with a mixed methods approach. ASSESSMENT: Survey results revealed an increase in student self-efficacy (p<0.05) and positive perceptions of SMART. Qualitative findings suggest the program provided opportunities for students to develop strategies for practice, promoted an appreciation for the various roles pharmacists play in health care, and fostered an appreciation for the complexity of real-world practice. CONCLUSION: Early clinical experiences can enhance student learning and development while fostering an appreciation for pharmacy practice. PMID- 26839429 TI - Student Perceptions of a Flipped Pharmacotherapy Course. AB - OBJECTIVE: To evaluate student perception of the flipped classroom redesign of a required pharmacotherapy course. DESIGN: Key foundational content was packaged into interactive, text-based online modules for self-paced learning prior to class. Class time was used for active and applied-but primarily case-based learning. ASSESSMENT: For students with a strong preference for traditional lecture learning, the perception of the learning experience was negatively affected by the flipped course design. Module length and time required to complete preclass preparation were the most frequently cited impediments to learning. Students desired instructor-directed reinforcement of independently acquired knowledge to connect foundational knowledge and its application. CONCLUSION: This study illustrates the challenges and highlights the importance of designing courses to effectively balance time requirements and connect preclass and in-class learning activities. It underscores the crucial role of the instructor in bridging the gap between material learned as independent study and its application. PMID- 26839430 TI - Using Problem-Based Learning in a Chemistry Practical Class for Pharmacy Students and Engaging Them with Feedback. AB - OBJECTIVE: To introduce a new approach to problem-based learning (PBL) used in a medicinal chemistry practical class for pharmacy students. DESIGN: The chemistry practical class was based on independent studies by small groups of undergraduate students (4-5), who designed their own practical work, taking relevant professional standards into account. Students were guided by feedback and acquired a set of skills important for health-care professionals. The model was tailored to the application of PBL in a chemistry practical class setting for a large student cohort (150 students). The achievement of learning outcomes was based on the submission of relevant documentation, including a certificate of analysis, in addition to peer assessment. Some of the learning outcomes also were assessed in the final written examination. ASSESSMENT: The practical was assessed at several time points using detailed marking schemes in order to provide the students with feedback. Students were required to engage with the feedback to succeed in the practical. CONCLUSION: A novel PBL chemistry laboratory course for pharmacy students was successful in that self-reflective learning and engagement with feedback were encouraged, and students enjoyed the challenging learning experience. Essential skills for health-care professionals were also promoted. PMID- 26839432 TI - Back to the Future: Using an Old Mindset to Teach Our Students Professionalism. PMID- 26839431 TI - Professionalization in Pharmacy Education as a Matter of Identity. AB - Little research exists on the formation of professional identity in higher education health programs. Such programs may approach the teaching, learning, and assessment of professionalism based upon a suite of attitudes, values, and behaviors considered indicative of a practicing professional. During this transition, professional identity formation can be achieved through student engagement with authentic experiences and interaction with qualified professionals. This paper examines the shift toward identity formation as an essential element of professional education and considers its implications for pharmacy curriculum design. PMID- 26839433 TI - Response to Viewpoint - Point/Counterpoint: Should a Pharmacy Dean be a Pharmacist? PMID- 26839435 TI - A4: Access, Affordability, Accountability - and Acceleration Address of the 2014 2015 President to the Opening General Session at the AACP Annual Meeting. PMID- 26839439 TI - Causal inference with longitudinal outcomes and non-ignorable drop-out: Estimating the effect of living alone on cognitive decline. AB - In this paper we develop a model to estimate the causal effect of living arrangement (living alone versus living with someone) on cognitive decline based on a 15-year prospective cohort study, where episodic memory function is measured every five years. One key feature of the model is the combination of propensity score matching to balance confounding variables between the two living arrangement groups -in order to reduce bias due to unbalanced covariates at baseline, with a pattern mixture model for longitudinal data -in order to deal with non-ignorable drop-out. A fully Bayesian approach allows us to convey the uncertainty in the estimation of the propensity score and subsequent matching in the inference of the causal effect of interest. The analysis conducted here adds to previous studies in the literature concerning the protective effect of living with someone, by proposing a modeling approach treating living arrangement as an exposure. PMID- 26839440 TI - Direct C7 Functionalization of Tryptophan. Synthesis of Methyl (S)-2-((tert Butoxycarbonyl)amino)-3-(7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indol 3-yl)propanoate. PMID- 26839441 TI - An Integrated Bayesian Nonparametric Approach for Stochastic and Variability Orders in ROC Curve Estimation: An Application to Endometriosis Diagnosis. AB - In estimating ROC curves of multiple tests, some a priori constraints may exist, either between the healthy and diseased populations within a test or between tests within a population. In this paper, we proposed an integrated modeling approach for ROC curves that jointly accounts for stochastic and variability orders. The stochastic order constrains the distributional centers of the diseased and healthy populations within a test, while the variability order constrains the distributional spreads of the tests within each of the populations. Under a Bayesian nonparametric framework, we used features of the Dirichlet process mixture to incorporate these order constraints in a natural way. We applied the proposed approach to data from the Physician Reliability Study that investigated the accuracy of diagnosing endometriosis using different clinical information. To address the issue of no gold standard in the real data, we used a sensitivity analysis approach that exploited diagnosis from a panel of experts. To demonstrate the performance of the methodology, we conducted simulation studies with varying sample sizes, distributional assumptions and order constraints. Supplementary materials for this article are available online. PMID- 26839442 TI - Meeting the expectations of your heritage culture: Links between attachment orientations, intragroup marginalization and psychological adjustment. AB - Do insecurely attached individuals perceive greater rejection from their heritage culture? Few studies have examined the antecedents and outcomes of this perceived rejection - termed intragroup marginalization - in spite of its implications for the adjustment of cultural migrants to the mainstream culture. This study investigated whether anxious and avoidant attachment orientations among cultural migrants were associated with greater intragroup marginalization and, in turn, with lower subjective well-being and flourishing and higher acculturative stress. Anxious attachment was associated with heightened intragroup marginalization from friends and, in turn, with increased acculturative stress; anxious attachment was also associated with increased intragroup marginalization from family. Avoidant attachment was linked with increased intragroup marginalization from family and, in turn, with decreased subjective well-being. PMID- 26839443 TI - CINCH (confocal incoherent correlation holography) super resolution fluorescence microscopy based upon FINCH (Fresnel incoherent correlation holography). AB - FINCH holographic fluorescence microscopy creates high resolution super-resolved images with enhanced depth of focus. The simple addition of a real-time Nipkow disk confocal image scanner in a conjugate plane of this incoherent holographic system is shown to reduce the depth of focus, and the combination of both techniques provides a simple way to enhance the axial resolution of FINCH in a combined method called "CINCH". An important feature of the combined system allows for the simultaneous real-time image capture of widefield and holographic images or confocal and confocal holographic images for ready comparison of each method on the exact same field of view. Additional GPU based complex deconvolution processing of the images further enhances resolution. PMID- 26839444 TI - Reduced Histone H3 Acetylation in CD4(+) T Lymphocytes: Potential Mechanism of Latent Autoimmune Diabetes in Adults. AB - Aims. Latent autoimmune diabetes in adults (LADA) is the result of gene environment interactions. Histone acetylation regulates gene expression and maybe interpret how environmental factors modify LADA. Hence, we studied the histone acetylation patterns in CD4(+) T lymphocytes from LADA patients. Methods. Blood CD4(+) T lymphocytes from 28 patients with LADA and 28 healthy controls were obtained to detect histone H3 acetylation and H4 acetylation. The gene expression of histone acetyltransferases (P300 and CREBBP) and histone deacetylases (HDAC1, HDAC2, and HDAC7) was measured by real-time polymerase chain reaction (RT-PCR). Results. Compared to healthy controls, reduced global H3 acetylation was observed in LADA patients' CD4(+) T lymphocytes (P < 0.05). Global level of H4 acetylation was not statistically different. Among LADA, CD4(+) T lymphocytes H3 acetylation was associated with glycosylated hemoglobin (HbA1c) and GADA titer. Compared to healthy controls, the expression of histone acetyltransferases CREBBP in LADA patients was downregulated, and the expression of histone deacetylases HDAC1 and HDAC7 was upregulated. Conclusion. A concerted downregulation of histone H3 acetylation was found in CD4(+) T lymphocytes of LADA patients, and this might provide evidence of a novel epigenetic explanation for the pathogenesis of LADA and its complications. PMID- 26839445 TI - Postoperative CA19-9 Change Is a Useful Predictor of Intrahepatic Cholangiocarcinoma Survival following Liver Resection. AB - BACKGROUND: To investigate the clinical significance of the perioperative CA19-9 change for predicting survival in intrahepatic cholangiocarcinoma (ICC) patients treated with surgical resection. METHODS: We retrospectively reviewed the data from 74 ICC patients treated with surgical resection between April 2001 and July 2010. Perioperative CA19-9 (preoperative level, postoperative lowest level, and level at recurrence) levels were analyzed for patient distribution and survival. RESULTS: Before surgery, there were 45 patients who had high preoperative CA19-9 levels (>37 U/mL) and 29 who had normal levels (<=37 U/mL). Of 45 patients with high CA19-9 levels, 34 had normalized CA19-9 levels after resection and 11 had persistently high levels. Of 34 patients with normalized CA19-9 levels, 18 showed recurrence. Of 29 patients with normal preoperative levels, 15 showed recurrence. Multivariate analysis presented that old age (hazard ratio [HR] = 3.881, p < 0.01), persistently high postoperative CA19-9 level (HR = 4.41, p < 0.001), perineural invasion (HR = 3.073, p = 0.01), narrow resection margin (HR = 3.152, p = 0.05), and lymph node metastasis (HR = 3.427, p = 0.02) were significant independent risk factors for survival. CONCLUSIONS: Patients who have normalized CA19-9 levels postoperatively have longer survival outcomes. Therefore, normalized postoperative CA19-9 may be a useful clinical marker for ICC survival. PMID- 26839447 TI - Global Health: Where Do Physiotherapy and Rehabilitation Research Fit? PMID- 26839446 TI - Kruppel-Like Factor 4 Inhibits the Transforming Growth Factor-beta1-Promoted Epithelial-to-Mesenchymal Transition via Downregulating Plasminogen Activator Inhibitor-1 in Lung Epithelial Cells. AB - Transforming growth factor-beta (TGF-beta) signaling and TGF-beta-promoted epithelial-to-mesenchymal transition (EMT) have been postulated to be the common pathway causing pulmonary fibrosis. However, the up- or downstreaming markers of TGF-beta-induced EMT still need to be further recognized. In the present study, we investigated the regulation on Kruppel-like factor 4 (KLF-4) and plasminogen activator inhibitor-1 (PAI-1) by TGF-beta in the murine lung epithelial LA-4 cells and then examined the regulation of both markers in the TGF-beta-induced EMT by the PAI-1 knockdown or the KLF-4 overexpression. Our study indicated that TGF-beta induced EMT in mouse LA-4 lung epithelial cells via reducing E-cadherin, while promoting Collagen I and alpha-SMA. And PAI-1 was upregulated, whereas KLF 4 was downregulated in the TGF-beta-induced EMT model in LA-4 cells. Moreover, the siRNA-mediated PAI-1 knockdown inhibited the TGF-beta-induced EMT, whereas the adenovirus-medicated KLF-4 overexpression markedly reduced the PAI-1 expression and inhibited the TGF-beta-induced EMT in LA-4 cells. In conclusion, our study confirmed the downregulation of KLF-4 in the TGF-beta-induced EMT in LA 4 cells. And the KLF-4 overexpression significantly reduced the TGF-beta-induced PAI-1 and thus inhibited the TGF-beta-induced EMT in mouse lung epithelial LA-4 cells. It implies that KLF-4 might be a promising target for effective control of the pulmonary fibrosis. PMID- 26839448 TI - Mapping the Physiotherapy Profession in Saskatchewan: Examining Rural versus Urban Practice Patterns. AB - PURPOSE: People living in rural and remote regions need support to overcome difficulties in accessing health care. The objectives of the study were (1) to compare demographic characteristics, professional engagement indicators, and clinical characteristics between physiotherapists practising in rural settings and those practising in urban settings and (2) to map the distribution of physiotherapists in Saskatchewan. METHOD: This cross-sectional study used de identified data collected from the 2013 Saskatchewan College of Physical Therapists membership renewal (n=643), linked with the Saskatchewan Physiotherapy Association's (SPA) 2012 membership list and a list of physiotherapists who had served as clinical instructors. Employment location (rural vs. urban) was determined by postal code. RESULTS: Only 11.2% of Saskatchewan physiotherapists listed a rural primary employment location, and a higher density of physiotherapists per 10,000 people work in health regions with large urban centres. Compared with urban physiotherapists, rural physiotherapists are more likely to provide direct patient care, to provide care to people of all ages, and to have a mixed client level, and they are less likely to be SPA members. CONCLUSIONS: Rural and urban physiotherapists in Saskatchewan have different practice and professional characteristics. This information may have implications for health human resource recruitment and retention policies as well as advocacy for equitable access to physiotherapy care in rural and remote regions. PMID- 26839449 TI - [Not Available]. AB - PURPOSE: To prepare a Canadian French translation of the PEDro Scale under the proposed name l'Echelle PEDro, and to examine the validity of its content. METHODS: A modified approach of Vallerand's cross-cultural validation methodology was used, beginning with a parallel back-translation of the PEDro scale by both professional translators and clinical researchers. These versions were reviewed by an initial panel of experts (P1), who then created the first experimental version of l'Echelle PEDro. This version was evaluated by a second panel of experts (P2). Finally, 32 clinical researchers evaluated the second experimental version of l'Echelle PEDro, using a 5-point clarity scale, and suggested final modifications. RESULTS: The various items on the final version of l'Echelle PEDro show a high degree of clarity (from 4.0 to 4.7 on the 5-point scale). CONCLUSION: The four rigorous steps of the translation process have produced a valid Canadian French version of the PEDro scale. PMID- 26839450 TI - Development of a Questionnaire to Investigate Study Design Factors Influencing Participation in Gait Rehabilitation Research by People with Stroke: A Brief Report. AB - PURPOSE: The main objective of this study was to evaluate the feasibility of a newly developed questionnaire to assess the influence of study design on participation in gait rehabilitation research in a pilot test with individuals with stroke. A secondary objective was to investigate the relationship between participation in gait rehabilitation research and social and clinical factors of interest after stroke. METHODS: A questionnaire was developed with expert opinion and guidance from related previous research. The questionnaire was pilot tested in a group of 21 people with stroke, and social and clinical factors (including gait function) were collected. Gait function was assessed using a pressure sensitive mat; social and clinical characteristics were extracted from patient charts. Correlations were performed to investigate relationships between questionnaire responses and gait function, motor impairment, and chronicity; t tests were used to examine response differences between people with a caregiver at home and those without. RESULTS: A total of 21 people with stroke completed the questionnaire without difficulty; mean completion time was 7.2 (SD 3.5) minutes, with a range of responses across participants. Borderline significant associations were found between gait function and the number of studies in which a person would participate and between stroke chronicity and the location of studies in which a person would participate. CONCLUSIONS: A questionnaire to investigate the influence of study design factors on participation in rehabilitation research is feasible for administration in the post-stroke population and has potential to inform the design of future studies. PMID- 26839451 TI - Evidence-Based Management of Postural Control in a Child with Cerebral Palsy. AB - The authors review and discuss the evidence exploring the use of dynamic compression garments with children with cerebral palsy. The evidence is presented in case-study format with a focus on postural control and impact on involuntary movements. PMID- 26839452 TI - Intra- and Inter-session Reliability of Static and Dynamic Postural Control in Participants with and without Patellofemoral Pain Syndrome. AB - PURPOSE: To determine the intra- and inter-session reliability of balance performance in people with patellofemoral pain syndrome (PFPS) and matched controls. METHODS: In this methodological study, single-leg-stance performance of 15 participants with unilateral PFPS and 15 healthy matched controls was assessed using the Biodex Balance System (BBS) under 4 task difficulty levels (static and dynamic, with and without visual feedback). Intra-class correlation coefficients (ICCs), standard errors of measurement, and coefficients of variation were calculated for the overall stability index, anterior-posterior stability index, and medial-lateral stability index. RESULTS: Static and dynamic postural performance during single-leg stance showed moderate to very high reliability in the PFPS group (ICCs=0.53-0.96) and in healthy control participants (ICCs=0.51 0.91). Both measures were more reliable with eyes closed than with eyes open. CONCLUSION: BBS stability indices appear to have acceptable reliability in people with PFPS, particularly in more challenging conditions, and may be incorporated into the evaluation and rehabilitation of this patient group. PMID- 26839453 TI - Clinician's Commentary on Akhbari et al.(1). PMID- 26839454 TI - Reliability of the Berg Balance Scale as a Clinical Measure of Balance in Community-Dwelling Older Adults with Mild to Moderate Alzheimer Disease: A Pilot Study. AB - PURPOSE: To measure test-retest and interrater reliability of the Berg Balance Scale (BBS) in community-dwelling adults with mild to moderate Alzheimer disease (AD). Method : A sample of 15 adults (mean age 80.20 [SD 5.03] years) with AD performed three balance tests: the BBS, timed up-and-go test (TUG), and Functional Reach Test (FRT). Both relative reliability, using the intra-class correlation coefficient (ICC), and absolute reliability, using standard error of measurement (SEM) and minimal detectable change (MDC95) values, were calculated; Bland-Altman plots were constructed to evaluate inter-tester agreement. The test retest interval was 1 week. Results : For the BBS, relative reliability values were 0.95 (95% CI, 0.85-0.98) for test-retest reliability and 0.72 (95% CI, 0.31 0.91) for interrater reliability; SEM was 6.01 points and MDC95 was 16.66 points; and interrater agreement was 16.62 points. The BBS performed better in test retest reliability than the TUG and FRT, tests with established reliability in AD. Between 33% and 50% of participants required cueing beyond standardized instructions because they were unable to remember test instructions. Conclusions : The BBS achieved relative reliability values that support its clinical utility, but MDC95 and agreement values indicate the scale has performance limitations in AD. Further research to optimize balance assessment for people with AD is required. PMID- 26839455 TI - Physiotherapy Management of People Diagnosed with de Quervain's Disease: A Case Series. AB - Purpose : To report the outcomes of a physiotherapy management approach for de Quervain's disease (DQD), a common hand disorder for which evidence for physiotherapy management is lacking, in 4 consecutive patients with DQD. Methods : Participants underwent a median of eight treatment sessions, consisting of mobilizations with movement, eccentric muscle training, and high-voltage electrical stimulation. Outcomes were assessed with an 11-point numeric pain rating scale (NPRS; range 1-10) and the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH; range 0%-100%). Result s: Median NPRS and DASH scores decreased from a baseline of 5 and 48, respectively, to 2.8 and 19 after treatment; at 6-month follow-up, all participants reported minimal pain and disability, but one participant required a corticosteroid injection shortly after discharge from physiotherapy. Conclusions : Overall outcome was considered successful for three of four patients, comparable to the success rate previously reported for corticosteroid injections. A randomized clinical trial evaluating the efficacy of this intervention seems warranted. PMID- 26839456 TI - Length of Stay and Achievement of Functional Milestones in a Rural First Nations Population in Northwestern Ontario during Acute-Care Admission after Total Hip Replacement: A Retrospective Chart Review. AB - PURPOSE: To understand the postoperative acute-care physiotherapy course for First Nations people returning after total hip replacement (THR) to remote communities with limited rehabilitation services and to evaluate length of stay and attainment of functional milestones after THR to determine to what extent an urban-based clinical pathway is transferrable to and effective for First Nations patients in a rural setting. METHODS: Data were collected retrospectively by reviewing charts of patients who underwent THR in the Northwest Ontario catchment area from 2007 through 2012. RESULTS: For the 36 patient charts reviewed, median length of stay (LOS) at the Sioux Lookout Meno Ya Win Health Centre (SLMHC) was 7.5 days (range 2-335); median LOS from time of surgery at the regional hospital (Thunder Bay Regional Health Centre) to discharge from SLMHC was 13.5 days; and median time for mobilizing and stairs was 9 days (range 1-93). CONCLUSION: Commonly accepted urban clinical pathways are not a good fit for smaller rural hospitals from which First Nations patients return to remote communities without rehabilitation services. LOS in a rural acute-care facility is similar to LOS in an urban rehabilitation facility. PMID- 26839458 TI - Clinician's Commentary on Farrell et al.(1). PMID- 26839457 TI - Use of Clinical Anatomy Resources by Musculoskeletal Outpatient Physiotherapists in Australian Public Hospitals: A Cross-Sectional Study. AB - PURPOSE: To investigate how musculoskeletal outpatient physiotherapists in public hospitals interact with and perceive clinical anatomy resources in the workplace. METHOD: This cross-sectional study used a postal survey sent to musculoskeletal outpatient physiotherapists in 64 Australian public hospitals. Survey questions examined demographics, qualifications, experience, types of resources used, whether resources meet requirements, and what improvements could be made to current resources. RESULTS: A total of 193 physiotherapists responded (75% response rate; 60% female), of whom 49% were age 35 years or younger; 67% had only an undergraduate qualification, and 37% had practised for 5 years or less. More experienced physiotherapists used resources significantly less frequently ([odds ratio]=1.35; 95% CI, 1.17-1.57), and we found no significant associations between preference for online versus printed resources and age, sex, qualifications, or experience. Trends included less experienced physiotherapists identifying the absence of online access as a barrier to resource use and provision of improved online facilities as necessary to improve access to clinical anatomy resources. CONCLUSION: RESULTS indicate distinct trends in physiotherapists' use of clinical anatomy resources, including a desire for improved online resource access on the part of less experienced physiotherapists. The findings are relevant to hospital outpatient clinics, particularly those that employ less experienced physiotherapists. PMID- 26839460 TI - Clinician's Commentary on Mori et al.(1). PMID- 26839459 TI - Development of the Canadian Physiotherapy Assessment of Clinical Performance: A New Tool to Assess Physiotherapy Students' Performance in Clinical Education. AB - PURPOSE: To develop the first draft of a Canadian tool to assess physiotherapy (PT) students' performance in clinical education (CE). Phase 1: to gain consensus on the items within the new tool, the number and placement of the comment boxes, and the rating scale; Phase 2: to explore the face and content validity of the draft tool. METHODS: Phase 1 used the Delphi method; Phase 2 used cognitive interviewing methods with recent graduates and clinical instructors (CIs) and detailed interviews with clinical education and measurement experts. RESULTS: Consensus was reached on the first draft of the new tool by round 3 of the Delphi process, which was completed by 21 participants. Interviews were completed with 13 CIs, 6 recent graduates, and 7 experts. Recent graduates and CIs were able to interpret the tool accurately, felt they could apply it to a recent CE experience, and provided suggestions to improve the draft. Experts provided salient advice. CONCLUSIONS: The first draft of a new tool to assess PT students in CE, the Canadian Physiotherapy Assessment of Clinical Performance (ACP), was developed and will undergo further development and testing, including national consultation with stakeholders. Data from Phase 2 will contribute to developing an online education module for CIs and students. PMID- 26839462 TI - What Does the Cochrane Collaboration Say about Exercise for People Living with Cancer? PMID- 26839461 TI - Physical Activity Participation and Preferences: Developmental and Oncology Related Transitions in Adolescents Treated for Cancer. AB - PURPOSE: To describe motor function and participation in, barriers to, and preferences for physical activity (PA) in adolescents during and after treatment of cancer and to discuss PA promotion in the context of developmental and cancer transitions. METHOD: A cross-sectional survey study used the Transfer and Basic Mobility and Sports/Physical Functioning self-report and parent-report scales of the Pediatric Outcomes Data Collection Instrument (PODCI) and questions about PA participation and preferences to collect information from 80 adolescents and 63 parents. RESULTS: PODCI scores for adolescents receiving treatment were more variable and significantly lower than those of adolescents who had been off treatment for more than 2 years. Fatigue, pain, general health, and doctor's orders were frequently identified as barriers to PA for adolescents receiving treatment. Many did not achieve recommended levels of PA. The adolescents expressed preferences for being active with friends and family, at home or in school, in the afternoon or evening, and through daily recreational and sports activities typical of teenagers. CONCLUSIONS: Physical abilities and participation in and barriers to PA vary across the cancer journey. Interventions should be sensitive to variability and acknowledge individual preferences and environments throughout the trajectories and transitions of cancer treatment and youth development to achieve lifelong healthy lifestyles. PMID- 26839463 TI - Sex Differences in the Study of Neurological Illnesses. PMID- 26839464 TI - Gene Expression Profiling of IL-17A-Treated Synovial Fibroblasts from the Human Temporomandibular Joint. AB - Synovial fibroblasts contribute to the inflammatory temporomandibular joint under pathogenic stimuli. Synovial fibroblasts and T cells participate in the perpetuation of joint inflammation in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other. IL-17 is an inflammatory cytokine produced primarily by Th17 cells which plays critical role in the pathogenesis of numerous autoimmune and inflammatory diseases. Here, we investigated the roles of IL-17A in temporomandibular joint disorders (TMD) using genome-wide analysis of synovial fibroblasts isolated from patients with TMD. IL 17 receptors were expressed in synovial fibroblasts as assessed using real-time PCR. Microarray analysis indicated that IL-17A treatment of synovial fibroblasts upregulated the expression of IL-6 and chemokines. Real-time PCR analysis showed that the gene expression of IL-6, CXCL1, IL-8, and CCL20 was significantly higher in IL-17A-treated synovial fibroblasts compared to nontreated controls. IL-6 protein production was increased by IL-17A in a time- and a dose-dependent manner. Additionally, IL-17A simulated IL-6 protein production in synovial fibroblasts samples isolated from three patients. Furthermore, signal inhibitor experiments indicated that IL-17-mediated induction of IL-6 was transduced via activation of NFkappaB and phosphatidylinositol 3-kinase/Akt. These results suggest that IL-17A is associated with the inflammatory progression of TMD. PMID- 26839466 TI - Validation of the Korean Version of Schedule of Fatigue and Anergia: General Physician Questionnaire. AB - The Schedule of Fatigue and Anergy/General Physician (SOFA/GP) was developed to screen for prolonged fatigue in the primary care setting. We aimed to evaluate the reliability and validity of the Korean version of the SOFA/GP (SOFA/GP-K), which is adapted from the original English version. We performed translation and back translation, and after conducting a pilot study, we tested the final version of the questionnaire for its reliability and validity in a Korean primary care setting. Two hundred participants that visited a health examination center in a university hospital completed the survey between September and November 2012. A second survey was performed within 2 weeks of the primary survey to test for reliability. We evaluated concurrent validity between the SOFA/GP-K score, the Fatigue Severity Scale (FSS), and Brief Fatigue Index (BFI) scores. The Spearman correlation coefficient between SOFA/GP-K and FSS was 0.71 and 0.61 between SOFA/GP-K and BFI. Internal consistency of SOFA/GP-K was observed (Cronbach's alpha = 0.82) and construct validity was confirmed by factor analysis. The Kappa scores for test-retest reliability for each survey item were between 0.28 and 0.64. The SOFA/GP-K is a valid and reliable questionnaire for screening fatigue in a primary care setting. PMID- 26839467 TI - The Perceived Socioeconomic Status Is an Important Factor of Health Recovery for Victims of Occupational Accidents in Korea. AB - We aimed to examine whether there is a correlation between the health recovery of industrial accident victims and their perceived socioeconomic status. Data were obtained from the first Panel Study of Worker's Compensation Insurance, which included 2,000 participants. We performed multivariate regression analysis and determined the odds ratios for participants with a subjectively lower socioeconomic status and for those with a subjectively lower middle socioeconomic status using 95% confidence intervals. An additional multivariate regression analysis yielded the odds ratios for participants with a subjectively lower socioeconomic status and those with a subjectively upper middle socioeconomic class using 95% confidence intervals. Of all participants, 299 reported a full recovery, whereas 1,701 did not. We examined the odds ratio (95% confidence intervals) for participants' health recovery according to their subjective socioeconomic status while controlling for sex, age, education, tobacco use, alcohol use, subjective state of health prior to the accident, chronic disease, employment duration, recovery period, accident type, disability status, disability rating, and economic participation. The odds of recovery in participants with a subjectively lower middle socioeconomic status were 1.707 times greater (1.264-2.305) than that of those with a subjectively lower socioeconomic status. Similarly, the odds of recovery in participants with a subjectively upper middle socioeconomic status were 3.124 times greater (1.795 5.438) than that of those with a subjectively lower socioeconomic status. Our findings indicate that participants' perceived socioeconomic disparities extend to disparities in their health status. The reinforcement of welfare measures is greatly needed to temper these disparities. PMID- 26839468 TI - Differentiation of Human Dental Pulp Stem Cells into Dopaminergic Neuron-like Cells in Vitro. AB - We investigated the potential of human dental pulp stem cells (hDPSCs) to differentiate into dopaminergic neurons in vitro as an autologous stem cell source for Parkinson's disease treatment. The hDPSCs were expanded in knockout embryonic stem cell (KO-ES) medium containing leukemia inhibitory factor (LIF) on gelatin-coated plates for 3-4 days. Then, the medium was replaced with KO-ES medium without LIF to allow the formation of the neurosphere for 4 days. The neurosphere was transferred into ITS medium, containing ITS (human insulin transferrin-sodium) and fibronectin, to select for Nestin-positive cells for 6-8 days. The cells were then cultured in N-2 medium containing basic fibroblast growth factor (FGF), FGF-8b, sonic hedgehog-N, and ascorbic acid on poly-l ornithine/fibronectin-coated plates to expand the Nestin-positive cells for up to 2 weeks. Finally, the cells were transferred into N-2/ascorbic acid medium to allow for their differentiation into dopaminergic neurons for 10-15 days. The differentiation stages were confirmed by morphological, immunocytochemical, flow cytometric, real-time PCR, and ELISA analyses. The expressions of mesenchymal stem cell markers were observed at the early stages. The expressions of early neuronal markers were maintained throughout the differentiation stages. The mature neural markers showed increased expression from stage 3 onwards. The percentage of cells positive for tyrosine hydroxylase was 14.49%, and the amount was 0.526 +/- 0.033 ng/mL at the last stage. hDPSCs can differentiate into dopaminergic neural cells under experimental cell differentiation conditions, showing potential as an autologous cell source for the treatment of Parkinson's disease. PMID- 26839469 TI - Patients Presenting with Advanced Human Immunodeficiency Virus Disease: Epidemiological Features by Age Group. AB - We explored factors influencing presentation with advanced human immunodeficiency virus (HIV) disease by age group. Data were derived from a city-wide cross sectional survey of 759 HIV-infected adults living in Seoul, Korea. The significance of each observed factor was assessed via multivariate logistic regression. Of subjects aged 20-34 years, lower educational level had a positive influence on presentation with advanced HIV disease (adjusted odds ratio [aOR], 2.43; 95% confidence interval [CI], 1.36-4.34); those recently diagnosed with HIV were more likely to be presented with advanced HIV disease (aOR, 3.17; 95% CI, 0.99-10.2). Of the subjects aged 35-49 years, those w ith advanced HIV disease were more likely to have been diagnosed during health check-ups (aOR, 2.91; 95% CI, 1.15-7.32) or via clinical manifestations (aOR, 3.61; 95% CI, 1.39-9.36). Of the subjects aged >= 50 years, presentation with advanced HIV disease was significantly more common in older subjects (aOR per increment of 5 years, 2.06; 95% CI, 1.32-3.23) and less common among individuals diagnosed with HIV in 2000 2006 (aOR, 0.18; 95% CI, 0.04-0.83). In conclusion, a lower educational level in younger subjects and more advanced age in older subjects positively influence the presentation of advanced HIV disease. PMID- 26839470 TI - Clinical Evaluation of Rapid Diagnostic Test Kit Using the Polysaccharide as a Genus-Specific Diagnostic Antigen for Leptospirosis in Korea, Bulgaria, and Argentina. AB - Leptospirosis, a zoonotic disease that is caused by many serovars which are more than 200 in the world, is an emerging worldwide disease. Accurate and rapid diagnostic tests for leptospirosis are a critical step to diagnose the disease. There are some commercial kits available for diagnosis of leptospirosis, but the obscurity of a species- or genus-specific antigen of pathogenic Leptospira interrogans causes the reduced sensitivity and specificity. In this study, the polysaccharide derived from lipopolysaccharide (LPS) of nonpathogenic Leptospira biflexa serovar patoc was prepared, and the antigenicity was confirmed by immunoblot and enzyme linked immunosorbent assay (ELISA). The performance of the rapid diagnostic test (RDT) kit using the polysaccharide as a diagnostic antigen was evaluated in Korea, Bulgaria and Argentina. The sensitivity was 93.9%, 100%, and 81.0% and the specificity was 97.9%, 100%, and 95.4% in Korea (which is a rare region occurring with 2 serovars mostly), Bulgaria (epidemic region with 3 serovars chiefly) and Argentina (endemic region with 19 serovars mainly) respectively. These results indicate that this RDT is applicable for global diagnosis of leptospirosis. This rapid and effective diagnosis will be helpful for diagnosis and manage of leptospirosis to use and the polysaccharide of Leptospira may be called as genus specific antigen for diagnosis. PMID- 26839471 TI - The Significance of Ectopic Germinal Centers in the Minor Salivary Gland of Patients with Sjogren's Syndrome. AB - We investigated the clinical and biological significance of germinal centers (GC) present in the minor salivary glands of patients with Sjogren's syndrome (SS). Minor salivary gland tissue biopsies from 93 patients with SS were used to identify GC-like structures, which were confirmed by CD21-positive follicular dendritic cell networks. Patients were compared based upon sociodemographics, glandular and extraglandular manifestations, and laboratory findings including autoantibody profiles, complement, and immunoglobulin levels; EULAR SS disease activity index (ESSDAI) and SS disease damage index (SSDDI) were also measured. GC-like structures were observed in 28 of 93 SS patients (30.1%). Mean focus scores and CRP levels were significantly higher in GC-positive patients than in GC-negative patients; GC-positive patients also exhibit a higher prevalence of rheumatoid factor and anti-SS-A/Ro antibodies compared to GC-negative patients. No differences in glandular or extra-glandular manifestations were evident between groups. In conclusion, SS patients with GC-like structures in the minor salivary glands exhibited laboratory profiles significantly different from those of their GC-negative counterparts. Long-term follow-up of these patients will be necessary to determine whether these laboratory abnormalities are predictive of clinical outcomes. PMID- 26839472 TI - Clinical and Genetic Features of Korean Patients with Recurrent Fever and Multi System Inflammation without Infectious or Autoimmune Evidence. AB - Autoinflammatory disease (AID) is a newly proposed category of disorders characterized by unprovoked episodes of inflammation without any infectious or autoimmune evidence. We aimed to characterize the clinical and genetic features of patients who had recurrent fever and multi-system inflammation but remain unclassified for any established AIDs. Medical records of 1,777 patients who visited our Rheumatology Clinic between March 2009 and December 2010 were reviewed to identify those who met the following criteria; 1) presence of fever, 2) inflammation in two or more organ systems, 3) recurrent nature of fever or inflammation, 4) no evidence of infection or malignancy, 5) absence of high titer autoantibodies, and 6) failure to satisfy any classification criteria for known AIDs. Genotyping was performed for common missense variants in MEFV, NOD2/CARD15, and TNFRSF1A. A small number of patients (17/1,777, 0.95%) were identified to meet the above criteria. Muco-cutaneous and musculoskeletal features were most common, but there was a considerable heterogeneity in symptom combination. Although they did not satisfy any established classification criteria for AIDs, substantial overlap was observed between the clinical spectrum of these patients and known AIDs. According to the newly proposed Eurofever criteria for periodic fevers, eleven of them were classified as TNF receptor-associated periodic syndrome and two as mevalonate kinase deficiency. However, no examined genetic variants including those in TNFRSF1A were found in these patients. A new set of classification criteria needs to be developed and validated for Asian patients with unclassified AIDs. PMID- 26839473 TI - The Effects of Rituximab on Lipids, Arterial Stiffness and Carotid Intima-Media Thickness in Rheumatoid Arthritis. AB - The aim of the study was to examine lipid profiles, arterial stiffness (AS), carotid intima-media thickness (cIMT), in 55 women with RA without overt cardiovascular disease (SVD) treated with rituximab (RTX).The following parameters were recorded before and 24 weeks after RTX therapy (2 infusions of 500 or 1,000 mg RTX intravenously, fortnightly): plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, DAS 28-ESR, serum C-reactive protein (CRP), RF IgM, AS (SI - stiffness index, RI - reflection index) by digital volume pulse contour analysis (Micro Medical, UK), and common cIMT by high-resolution B-mode carotid ultrasound. Based on the European League Against Rheumatism (EULAR) criteria, patients were divided into two groups: 1) moderate/good response to RTX therapy after 24 weeks (41 patients, 75%), 2) no response to RTX therapy (14 patients, 25%). Effective RTX therapy resulted in 9% increase in TC, 23% increase in HDL-C and 14% decrease in atherogenic index, 57% decrease in SI and 24% decrease in RI. We observed a 9% decrease of cIMTmax at 24 weeks. The improvement of cardiovascular parameters was accompanied by statistically significant decreases of CRP, ESR, RF IgM and DAS 28 in group 1 (P < 0.05). There were not significant changes in lipid profile, AS parameters, and cIMT in group 2. Two infusions of RTX in case of moderate/good EULAR effect of therapy exerted favorable effects on lipid profile, AS and cIMT in women with RA without overt CVD. PMID- 26839474 TI - Factor V Deficiency in Korean Patients: Clinical and Laboratory Features, Treatment, and Outcome. AB - Due to rarity of factor V (FV) deficiency, there have been only a few case reports in Korea. We retrospectively analysed the clinical-laboratory features of FV deficiency in 10 Korean patients. Between January 1987 and December 2013, 10 case reports published in a Korean journal or proceedings of Korea Society on Thrombosis and Hemostasis were reviewed. Severity is defined as mild (> 5% of factor activity), moderate (1%-5%), and severe (< 1%). The median age at diagnosis, six males and four females, was 26 years (range, 1 month-73 years). Six of 10 patients were classified as moderate, three as mild, and one as severe disease. Eight patients were diagnosed as inherited FV deficiency. The most frequent symptoms were mucosal tract bleedings (40%) such as epistaxis, and menorrhagia in female. Hemarthroses and postoperative bleeding occurred in one and four patients, respectively. Life-threatening bleeding episodes occurred in the peritoneal cavity (n = 2), central nerve system (n = 1), and retroperitoneal space (n = 1). No lethal haemorrhages happened to patients with mild disease. The majority of bleeding episodes were controlled with local measures and fresh frozen plasma replacement. Two acquired FV deficient-patients showing life threatening haemorrhages received the immunosuppressive therapy, but one of them died from postoperative bleeding complications. Despite the small sample size of this study due to rarity of the disease, we found that Korean patients with FV deficiency had similar clinical manifestations and treatment outcomes shown in previous studies. PMID- 26839475 TI - Predictive Factors of Mortality in Population of Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH): Results from a Korean PNH Registry. AB - Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, systemic, life threatening disease, characterized by chronic uncontrolled complement activation. A retrospective analysis of 301 Korean PNH patients who had not received eculizumab was performed to systematically identify the clinical symptoms and signs predictive of mortality. PNH patients with hemolysis (lactate dehydrogenase [LDH] >= 1.5 * the upper limit of normal [ULN]) have a 4.8-fold higher mortality rate compared with the age- and sex-matched general population (P < 0.001). In contrast, patients with LDH < 1.5 * ULN have a similar mortality rate as the general population (P = 0.824). Thromboembolism (TE) (odds ratio [OR] 7.11; 95% confidence interval [CI] (3.052-16.562), renal impairment (OR, 2.953; 95% CI, 1.116-7.818) and PNH-cytopenia (OR, 2.547; 95% CI, 1.159-5.597) are independent risk factors for mortality, with mortality rates 14-fold (P < 0.001), 8-fold (P < 0.001), and 6.2-fold (P < 0.001) greater than that of the age- and sex-matched general population, respectively. The combination of hemolysis and 1 or more of the clinical symptoms such as abdominal pain, chest pain, or dyspnea, resulted in a much greater increased mortality rate when compared with patients with just the individual symptom alone or just hemolysis. Early identification of risk factors related to mortality is crucial for the management of PNH. This trial was registered at www.clinicaltrials.gov as NCT01224483. PMID- 26839477 TI - In-Silico Trials for Glucose Control in Hospitalized Patients with Type 2 Diabetes. AB - Although various basal-bolus insulin therapy (BBIT) protocols have been used in the clinical environment, safer and more effective BBIT protocols are required for glucose control in hospitalized patients with type 2 diabetes (T2D). Modeling approaches could provide an evaluation environment for developing the optimal BBIT protocol prior to clinical trials at low cost and without risk of danger. In this study, an in-silico model was proposed to evaluate subcutaneous BBIT protocols in hospitalized patients with T2D. The proposed model was validated by comparing the BBIT protocol and sliding-scale insulin therapy (SSIT) protocol. The model was utilized for in-silico trials to compare the protocols of adjusting basal-insulin dose (BBIT1) versus adjusting total-daily-insulin dose (BBIT2). The model was also used to evaluate two different initial total-daily-insulin doses for various levels of renal function. The BBIT outcomes were superior to those of SSIT, which is consistent with earlier studies. BBIT2 also outperformed BBIT1, producing a decreased daily mean glucose level and longer time-in-target-range. Moreover, with a standard dose, the overall daily mean glucose levels reached the target range faster than with a reduced-dose for all degrees of renal function. The in-silico studies demonstrated several significant findings, including that the adjustment of total-daily-insulin dose is more effective than changes to basal-insulin dose alone. This research represents a first step toward the eventual development of an advanced model for evaluating various BBIT protocols. PMID- 26839476 TI - Improving Effect of the Acute Administration of Dietary Fiber-Enriched Cereals on Blood Glucose Levels and Gut Hormone Secretion. AB - Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP 1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5+/-12.8 vs. 245.9+/-15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8+/-9.1 vs. 140.3+/-14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281). PMID- 26839478 TI - The Effect of Sleep Quality on the Development of Type 2 Diabetes in Primary Care Patients. AB - Sleep has important effects on physical and mental health, and sleep disorders are associated with increased mortality and morbidity. This study was conducted to evaluate the relationship between sleep duration or sleep quality and the risk of type 2 diabetes. The FACTS (FAmily CohorT Study in primary care) was established to investigate the relations between familial environment and health which was conducted at 22 family medicine outpatient clinics in general hospitals. Total 563 patients without diabetes who received >=1 year follow-up examination were included in the analysis. We used the Pittsburgh Sleep Quality Index to determine sleep quality, and a score of >=5 was considered to define poor sleep quality. Patients taking oral hypoglycemic agents, having a fasting glucose level of >126 mg/dL, or diagnosed with diabetes by physicians were classified as having diabetes. The median follow-up period was 2.5 years. Poor sleep quality was associated with a higher risk of diabetes after adjusting for age, sex, body mass index, income, physical activity, and family history of diabetes (relative risk=2.64; 95% confidence interval, 1.03-6.78). As a risk factor for the development of diabetes, poor sleep quality may independently increase the incidence of diabetes. PMID- 26839479 TI - Clinical Characteristics and Factors Influencing the Occurrence of Acute Eosinophilic Pneumonia in Korean Military Personnel. AB - Acute eosinophilic pneumonia (AEP) is an uncommon inflammatory lung disease, and limited data exist concerning the clinical characteristics and factors that influence its occurrence. We retrospectively reviewed the records of AEP patients treated at Korean military hospitals between January 2007 and December 2013. In total, 333 patients were identified; their median age was 22 years, and all were men. All patients presented with acute respiratory symptoms (cough, sputum, dyspnea, or fever) and had elevated levels of inflammatory markers including median values of 13,185/uL for white blood cell count and 9.51 mg/dL for C reactive protein. All patients showed diffuse ground glass opacity/consolidation, and most had pleural effusion (n = 265; 80%) or interlobular septal thickening (n = 265; 85%) on chest computed tomography. Most patients had normal body mass index (n = 255; 77%), and only 30 (9%) patients had underlying diseases including rhinitis, asthma, or atopic dermatitis. Most patients had recently changed smoking habits (n = 288; 87%) and were Army personnel (n = 297; 89%).The AEP incidence was higher in the Army group compared to the Navy or Air Force group for every year (P = 0.002). Both the number of patients and patients with high illness severity (oxygen requirement, intensive care unit admission, and pneumonia severity score class >= III) tended to increase as seasonal temperatures rose. We describe the clinical characteristics of AEP and demonstrate that AEP patients have recently changed smoking habits and work for the Army. There is an increasing tendency in the numbers of patients and those with higher AEP severity with rising seasonal temperatures. PMID- 26839480 TI - Predictors of Default from Treatment for Tuberculosis: a Single Center Case Control Study in Korea. AB - Default from tuberculosis (TB) treatment could exacerbate the disease and result in the emergence of drug resistance. This study identified the risk factors for default from TB treatment in Korea. This single-center case-control study analyzed 46 default cases and 100 controls. Default was defined as interrupting treatment for 2 or more consecutive months. The reasons for default were mainly incorrect perception or information about TB (41.3%) and experience of adverse events due to TB drugs (41.3%). In univariate analysis, low income (< 2,000 US dollars/month, 88.1% vs. 68.4%, P = 0.015), absence of TB stigma (4.3% vs. 61.3%, P < 0.001), treatment by a non-pulmonologist (74.1% vs. 25.9%, P < 0.001), history of previous treatment (37.0% vs. 19.0%, P = 0.019), former defaulter (15.2% vs. 2.0%, P = 0.005), and combined extrapulmonary TB (54.3% vs. 34.0%, P = 0.020) were significant risk factors for default. In multivariate analysis, the absence of TB stigma (adjusted odd ratio [aOR]: 46.299, 95% confidence interval [CI]: 8.078-265.365, P < 0.001), treatment by a non-pulmonologist (aOR: 14.567, 95% CI: 3.260-65.089, P < 0.001), former defaulters (aOR: 33.226, 95% CI: 2.658 415.309, P = 0.007), and low income (aOR: 5.246, 95% CI: 1.249-22.029, P = 0.024) were independent predictors of default from TB treatment. In conclusion, patients with absence of disease stigma, treated by a non-pulmonologist, who were former defaulters, and with low income should be carefully monitored during TB treatment in Korea to avoid treatment default. PMID- 26839481 TI - Sleep Patterns among South Korean Infants and Toddlers: Global Comparison. AB - The purpose of this study was to examine sleep patterns in a large sample of infants and toddlers (ages birth to 36 months) in Korea, and to compare sleep patterns, sleep problems, sleep ecology, and parental behaviors to global sleep data on young children in both predominantly Asian (P-A) and predominantly Caucasian (P-C) countries/regions. We additionally examined parent and child demographic information, parental behaviors, and aspects of the sleep ecology as predictors of sleep patterns among infants and toddlers in Korea. Parents/caregivers of 1,036 Korean infants and toddlers completed an expanded, internet-based version of the brief infant sleep questionnaire. Consistent with other studies of sleep in early childhood, sleep/wake patterns became increasingly consolidated with older child age for the Korea sample. Compared to both P-A and P-C infants and toddlers, children in Korea had the latest bedtimes, shortest total sleep and daytime sleep durations, and the least frequent rates of napping. Even though half of parents perceive their children's sleep problematic, parental perceptions of severe child sleep problems were the lowest. Within Korea, breastfeeding and bottle-feeding at sleep resumption were associated with increased nocturnal awakenings. Evening television viewing was associated with later bedtimes, which may have implications for sleep hygiene recommendations in clinical practice. The current study provides important information about sleep/wake patterns, parental behaviors, and aspects of the sleep ecology for infants and toddlers for physicians to support healthy sleep in Korea. PMID- 26839482 TI - Screening and Identifying Erosive Esophagitis in Children with Non-cardiac Chest Pain. AB - Non-cardiac chest pain is a common disorder that leads to costly evaluations to distinguish it from cardiac pain. The present study aimed to clarify the clinical characteristics of erosive esophagitis in children with non-cardiac chest pain. Ninety nine patients (mean age, 9.55 +/- 2.95 years, 49 girls) with non-cardiac chest pain were enrolled. Patients were classified into two groups: erosive esophagitis and non-erosive esophagitis-related non-cardiac chest pain by esophagogastroduodenoscopy. Children in the erosive esophagitis-related non cardiac chest pain group were significantly older (10.95 +/- 2.54 years vs. 8.52 +/- 2.83 years). Multivariate logistic regression analysis identified the following predictors of gastroesophageal reflux: chest pain related to sleep (odds ratio = 18.05, 95% confidence interval: 3.18-102.49); unfavorable dietary habits (odds ratio = 7.11, 95% confidence interval: 1.53-32.87); chest pain related to food (odds ratio = 5.09, 95% confidence interval: 1.37-18.86); epigastric pain (odds ratio = 3.73, 95% confidence interval: 1.12-12.33); and nausea, vomiting, and/or regurgitation (odds ratio = 4.35, 95% confidence interval: 1.22-15.54). Gastroesophageal reflux disease should be considered first in children with non-cardiac chest pain. Children with gastroesophageal reflux disease should receive medical treatment and lifestyle modifications. PMID- 26839483 TI - Estrogen-mediated Height Control in Girls with Marfan Syndrome. AB - This study evaluated the efficacy of a stepwise regimen of estradiol valerate for height control in girls with Marfan syndrome. Eight girls with Marfan syndrome who had completed estrogen treatment for height control were included. Estradiol valerate was started at a dose of 2 mg/day, and then was increased. The projected final height was estimated using the initial height percentile (on a disease specific growth curve for Korean Marfan syndrome [gcPFHt]), and the initial bone age (baPFHt). After the estrogen treatment, the projected final height was compared to the actual final height (FHt). The median baseline chronological and bone age were 10.0 and 10.5 years, respectively. After a median of 36.5 months of treatment, the median FHt (172.6 cm) was shorter than the median gcPFHt (181.0 cm) and baPFHt (175.9 cm). In the six patients who started treatment before the age of 11 years, the median FHt (171.8 cm) was shorter than the median gcPFHt (181.5 cm) and baPFHt (177.4 cm) after treatment. The median differences between the FHt and gcPFHt and baPFHt were 9.2 and 8.3 cm, respectively. In two patients started treatment after the age of 11, the differences between FHt and gcPFHt, and baPFHt after treatment were -4 and 1.4 cm, and -1.2 and 0 cm for each case, respectively. A stepwise increasing regimen of estradiol valerate may be an effective treatment for height control in girls with Marfan syndrome, especially when started under 11 years old. PMID- 26839484 TI - Impaired Na(+)/K(+)-ATPase Function in Patients with Interstitial Cystitis/Painful Bladder Syndrome. AB - Na(+)/K(+)-ATPase (NKA) is abundantly expressed in the basolateral membrane of epithelial cells, which is necessary for tight junction formation. The tight junction is an urothelial barrier between urine and the underlying bladder. Impairment of tight junctions allows migration of urinary solutes in patients with interstitial cystitis/painful bladder syndrome (IC/PBS). We evaluated NKA expression and activity in bladder samples from patients with IC/PBS. The study group consisted of 85 patients with IC/PBS, and the control group consisted of 20 volunteers. Bladder biopsies were taken from both groups. We determined the expression and distribution of NKA using NKA activity assays, immunoblotting, immunohistochemical staining, and immunofluorescent staining. The protein levels and activity of NKA in the study group were significantly lower than the control group (1.08 +/- 0.06 vs. 2.39 +/- 0.29 and 0.60 +/- 0.04 vs. 1.81 +/- 0.18 umol ADP/mg protein/hour, respectively; P < 0.05). Additionally, immunofluorescent staining for detection of CK7, a marker of the bladder urothelium, predominantly colocalized with NKA in patients in the study group. Our results demonstrated the expression and activity of NKA were decreased in bladder biopsies of patients with IC/PBS. These findings suggest that NKA function is impaired in the bladders from patients with IC/PBS. PMID- 26839485 TI - Independent and Interactive Influences of the APOE Genotype and Beta-Amyloid Burden on Cognitive Function in Mild Cognitive Impairment. AB - This study aimed to investigate the independent and interactive influences of apolipoprotein E (APOE) epsilon4 and beta-amyloid (Abeta) on multiple cognitive domains in a large group of cognitively normal (CN) individuals and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Participants were included if clinical and cognitive assessments, amyloid imaging, and APOE genotype were all available from the Alzheimer's Disease Neuroimaging Initiative database (CN = 324, MCI = 502, AD = 182). Individuals with one or two copies of epsilon4 were designated as APOE epsilon4 carriers (epsilon4+); individuals with no epsilon4 were designated as APOE epsilon4 non-carriers (epsilon4-). Based on mean florbetapir standard uptake value ratios, participants were classified as Abeta burden-positive (Abeta+) or Abeta burden-negative (Abeta-). In MCI, APOE epsilon4 effects were predominantly observed on frontal executive function, with epsilon4+ participants exhibiting poorer performances; Abeta positivity had no influence on this effect. Abeta effects were observed on global cognition, memory, and visuospatial ability, with Abeta+ participants exhibiting poorer performances. Measures of frontal executive function were not influenced by Abeta. Interactive effects of APOE epsilon4+ and Abeta were observed on global cognition and verbal recognition memory. Abeta, not APOE epsilon4+, influenced clinical severity and functional status. The influences of APOE epsilon4+ and Abeta on cognitive function were minimal in CN and AD. In conclusion, we provide further evidence of both independent and interactive influences of APOE epsilon4+ and Abeta on cognitive function in MCI, with APOE epsilon4+ and Abeta showing dissociable effects on executive and non-executive functions, respectively. PMID- 26839486 TI - Skin Infection due to Trichophyton tonsurans Still Occurs in People in Korea but not as Outbreaks. AB - Since 1995, Trichophyton tonsurans has been one of the causative agents of dermatophytosis in Korea. Herein we evaluate 77 patients infected with T. tonsurans who visited an outpatient clinic between 2004 and 2014. Infections due to T. tonsurans were diagnosed by mycological examination, which included direct microscopic examination using 15% KOH and culture in potato dextrose agar complemented with 0.5% chloramphenicol. The annual prevalence of infection due to T. tonsurans was the highest in 2014 (15 cases) but remained constant in non gladiators between 2004 and 2014. The ratio of male to female patients was 1:0.3. The spring season presented the highest incidence compared with other seasons, with 27 cases. The incidence of infections due to T. tonsurans among gladiators was highest in spring compared with the other seasons whereas the incidence in non-gladiators was the highest in the winter. The body site most commonly affected was the face. Tinea corporis was the most common subtype of dermatophytosis caused by T. tonsurans. Herein, we demonstrate that the prevalence of infection with T. tonsurans remain constant throughout the study period in Korea. PMID- 26839487 TI - Falls in Korean Polio Survivors: Incidence, Consequences, and Risk Factors. AB - Falls and fall-related injuries are important issue among polio survivors. The purpose of this study was to determine the incidence of, and consequences and factors associated with falls among Korean polio survivors. A total of 317 polio survivors participated in this study. All participants completed a questionnaire including fall history, symptoms related to post-polio syndrome and other information through a telephone interview. Among them, 80 participants visited our clinic for additional physical measurements and tests. Of the 317 respondents, 68.5% reported at least one fall in the past year. Of the fallers, 42.5% experienced at least one fall during one month. Most falls occurred during ambulation (76.6%), outside (75.2%) and by slipping down (29.7%). Of fallers, 45% reported any injuries caused by falls, and 23.3% reported fractures specifically. Female sex, old age, low bone mineral density, the presence of symptoms related to post-polio syndrome (PPS), poor balance confidence, short physical performance battery and weak muscle strength of knee extensor were not significantly associated with falls. Only leg-length discrepancy using spine-malleolar distance (SMD) was a significant factor associated with falls among Korean polio survivors. Our findings suggest that malalignment between the paralytic and non paralytic limb length should be addressed in polio survivors for preventing falls. PMID- 26839488 TI - Genetic Polymorphism of CYP2D6 and Clomiphene Concentrations in Infertile Patients with Ovulatory Dysfunction Treated with Clomiphene Citrate. AB - CYP2D6 is primarily responsible for the metabolism of clomiphene citrate (CC). The purpose of the present study was to investigate the relationship between CYP2D6 genotypes, concentrations of CC and its major metabolites and drug response in infertility patients. We studied 42 patients with ovulatory dysfunction treated with only CC. Patients received a dose of 100 mg/day CC on days 3-7 of the menstrual cycle. CYP2D6 genotyping and measurement of CC and the major metabolite concentrations were performed. Patients were categorized into CC responders or non-responders according to one cycle response for the ovulation. Thirty-two patients were CC responders and 10 patients were non-responders with 1 cycle treatment. The CC concentrations were highly variable within the same group, but non-responders revealed significantly lower (E)-clomiphene concentration and a trend of decreased concentrations of active metabolites compared to the responders. Nine patients with intermediate metabolizer phenotype were all responders. We confirmed that the CC and the metabolite concentrations were different according to the ovulation status. However, our results do not provide evidence for the contribution of CYP2D6 polymorphism to either drug response or CC concentrations. PMID- 26839490 TI - Chronic Intussusception Caused by Diffuse Large B-Cell Lymphoma in a 6-Year-Old Girl Presenting with Abdominal Pain and Constipation for 2 Months. AB - The classical triad of abdominal pain, vomiting, and bloody stool is absent in chronic intussusception for more than 2 weeks. Here, we report a 6-year-old female with recurrent abdominal pain for 2 months. Ultrasonography of the abdomen revealed an ileocolic-type intussusception. The lesion accompanying the tight fibrous adhesion was treated by resection and ileocolic anastomosis. It was diagnosed as intussusception with diffuse large B-cell lymphoma. A high index of suspicion for abdominal pain in children should result in the correct diagnosis and appropriate management. PMID- 26839489 TI - Isolation of Middle East Respiratory Syndrome Coronavirus from a Patient of the 2015 Korean Outbreak. AB - During the 2015 outbreak of Middle East respiratory syndrome coronavirus (MERS CoV) in Korea, 186 persons were infected, resulting in 38 fatalities. We isolated MERS-CoV from the oropharyngeal sample obtained from a patient of the outbreak. Cytopathic effects showing detachment and rounding of cells were observed in Vero cell cultures 3 days after inoculation of the sample. Spherical virus particles were observed by transmission electron microscopy. Full-length genome sequence of the virus isolate was obtained and phylogenetic analyses showed that it clustered with clade B of MERS-CoV. PMID- 26839492 TI - Erratum: Effect of Prophylactic Palivizumab on Admission Due to Respiratory Syncytial Virus Infection in Former Very Low Birth Weight Infants with Bronchopulmonary Dysplasia. PMID- 26839491 TI - International Medical Mission Facing Global Increase of Chronic Disease: 2-Year Experience in Bangladesh. AB - Specialists of developing countries are facing the epidemic growth of noncommunicable diseases (NCDs). From 2011 to 2013, I, as a Korean volunteer doctor, had been working in a local primary healthcare center in Bangladesh, assessing rates of NCDs. Proportion of patients with NCDs was increased from 74.96% in 1999 to 83.05% in 2012, particularly due to the spreading of diabetes mellitus, cardiovascular diseases, and tuberculosis. To succeed in medical mission in developing countries, volunteer doctors have to take measures for preventing chronic diseases along with proper treatment. PMID- 26839493 TI - Notice of Retraction: Pak CS, et al. A Phase III, Randomized, Double-Blind, Matched-Pairs, Active-Controlled Clinical Trial and Preclinical Animal Study to Compare the Durability, Efficacy and Safety between Polynucleotide Filler and Hyaluronic Acid Filler in the Correction of Crow's Feet: A New Concept of Regenerative Filler. J Korean Med Sci 2014; 29(Suppl 3): S201-S209. PMID- 26839494 TI - Letter-Sound Reading: Teaching Preschool Children Print-to-Sound Processing. AB - This intervention study investigated the growth of letter sound reading and growth of consonant-vowel-consonant (CVC) word decoding abilities for a representative sample of 41 US children in preschool settings. Specifically, the study evaluated the effectiveness of a 3-step letter-sound teaching intervention in teaching pre-school children to decode, or read, single letters. The study compared a control group, which received the preschool's standard letter-sound instruction, to an intervention group which received a 3-step letter-sound instruction intervention. The children's growth in letter-sound reading and CVC word decoding abilities were assessed at baseline and 2, 4, 6 and 8 weeks. When compared to the control group, the growth of letter-sound reading ability was slightly higher for the intervention group. The rate of increase in letter-sound reading was significantly faster for the intervention group. In both groups, too few children learned to decode any CVC words to allow for analysis. Results of this study support the use of the intervention strategy in preschools for teaching children print-to-sound processing. PMID- 26839495 TI - The Social Environmental Elements of Resilience among Vulnerable African American/Black Men Who Have Sex with Men. AB - Resilience theory has been suggested as a strong framework for research on HIV prevention among men who have sex with men (MSM). Among this population, literature indicates that African American/Black MSM are particularly vulnerable to health and social disparities associated with HIV transmission risk. Conceptualizing resilience as a part of one's social environment, this qualitative study investigates the specific elements of resilience, and the associated contexts and relationships, among a sample of 21 substance-using African American/Black MSM. Data indicate that: 1) elements contributing to resilience are multiple and co-occurring, including inner strengths, social relationships, diversity of experience, religion/spirituality, altruism, and creativity; 2) as an element of resilience, social support was experienced differently among men who did and did not have supportive relationships with other gay and bisexual men, which has implications for social service provision and intervention approaches; and 3) diversity of experiences and relationships is an important influencing factor on expressions of resilience. Social services or interventions that facilitate the development of these elements of resilience will likely be especially beneficial for vulnerable African American/Black MSM. PMID- 26839496 TI - Diversity and Plant Growth Promoting Capacity of Endophytic Fungi Associated with Halophytic Plants from the West Coast of Korea. AB - Five halophytic plant species, Suaeda maritima, Limonium tetragonum, Suaeda australis, Phragmites australis, and Suaeda glauca Bunge, which are native to the Muan salt marsh of South Korea, were examined for fungal endophytes by sequencing the internal transcribed spacer (ITS) region containing ITS1, 5.8S rRNA, and ITS2. In total, 160 endophytic fungal strains were isolated and identified from the roots of the 5 plant species. Taxonomically, all 160 strains belonged to the phyla Ascomycota, Basidiomycota, and Zygomycota. The most dominant genus was Fusarium, followed by the genera Penicillium and Alternaria. Subsequently, using 5 statistical methods, the diversity indices of the endophytes were determined at genus level. Among these halophytic plants, P. australis was found to host the greatest diversity of endophytic fungi. Culture filtrates of endophytic fungi were treated to Waito-C rice seedlings for plant growth-promoting effects. The fungal strain Su-3-4-3 isolated from S. glauca Bunge provide the maximum plant length (20.1 cm) in comparison with wild-type Gibberella fujikuroi (19.6 cm). Consequently, chromatographic analysis of the culture filtrate of Su-3-4-3 showed the presence of physiologically active gibberellins, GA1 (0.465 ng/mL), GA3 (1.808 ng/mL) along with other physiologically inactive GA9 (0.054 ng/mL) and GA24 (0.044 ng/mL). The fungal isolate Su-3-4-3 was identified as Talaromyces pinophilus. PMID- 26839497 TI - Characterization and Pathogenicity of Alternaria burnsii from Seeds of Cucurbita maxima (Cucurbitaceae) in Bangladesh. AB - In the course of survey of endophytic fungi from Bangladesh pumpkin seeds in 2011~2012, two strains (CNU111042 and CNU111043) with similar colony characteristics were isolated and characterized by their morphology and by molecular phylogenetic analysis of the internal transcribed spacer, glyceraldehydes-3-phosphate dehydrogenase (gpd), and Alternaria allergen a1 (Alt a1) sequences. Phylogenetic analysis of all three sequences and their combined dataset revealed that the fungus formed a subclade within the A. alternata clade, matching A. burnsi and showing differences with its other closely related Alternaria species, such as A. longipes, A. tomato, and A. tomaticola. Long ellipsoid, obclavate or ovoid beakless conidia, shorter and thinner conidial size (16~60 [90] * 6.5~14 [~16] um) distinguish this fungus from other related species. These isolates showed more transverse septation (2~11) and less longitudinal septation (0~3) than did other related species. Moreover, the isolate did not produce any diffusible pigment on media. Therefore, our results reveal that the newly recorded fungus from a new host, Cucurbita maxima, is Alternaria burnsii Uppal, Patel & Kamat. PMID- 26839498 TI - Confirmation of Two Undescribed Fungal Species from Dokdo of Korea Based on Current Classification System Using Multi Loci. AB - Using dilution plating method, 47 fungal isolates were obtained from a soil sample collected from Dokdo in the East Sea of Korea in 2013. In this study, two fungal isolates, EML-MFS30-1 and EML-DDSF4, were confirmed as undescribed species, Metarhizium guizhouense and Mortierella oligospora in Korea based on current classification system using multi loci including rDNA internal transcribed spacer, large subunit, small subunit, and beta-tubulin (BTUB) genes. Herein, detailed morphological descriptions on characters of the undescribed fungal species as well as their molecular phylogenetic status are provided with comparisons to related species. PMID- 26839499 TI - Discovery of Two New Talaromyces Species from Crop Field Soil in Korea. AB - Two new fungal species of the genus Talaromyces, Talaromyces purpurogenus and Talaromyces trachyspermus from the Trichocomaceae family, were recovered during an investigation of fungal communities in soil collected from the Gangwon-do and Jeollanam-do provinces of Korea. These two species have not been previously officially reported from Korea. In this study, detailed descriptions of internal transcribed spacer rDNA and beta-tubulin gene regions of these two fungi are presented. Morphological features of the two fungi in five agar media, potato dextrose, oatmeal, malt extract, czapek yeast extract, and yeast extract sucrose, are also reported. The species were identified on the basis of molecular and morphological analysis, and herein we present data with detailed descriptions and figures. PMID- 26839501 TI - Functional Properties of Filamentous Fungi Isolated from the Indonesian Fermented Dried Cassava, with Particular Application on Poultry. AB - The study aimed to evaluate the probiotic properties, antioxidant activity and fermentative capacity of Acremonium charticola and Rhizopus oryzae isolated from the Indonesian fermented dried cassava, with particular application on poultry. A. charticola inhibited the growth of Escherichia coli and Aspergillus flavus. A. charticola and R. oryzae grew in potato dextrose agar (PDA) adjusted to pH 3 and 8 or in PDA supplemented with bile salt up to 0.8%. After soaking for 8 hr, the survival rate of A. charticola in the simulated gastric juice (pH 2) and bile solutions (2% bile salt) was lower than that of R. oryzae. A. charticola and R. oryzae exhibited strong antioxidant activities. Compared to unfermented cassava pulp (control), the fibre content of cassava pulp tended to be lower after fermentation with A. charticola for 14 days. The populations of A. charticola and R. oryzae were significantly higher in fermented cassava pulp than in unfermented one. Coliform was higher in cassava pulp fermented with R. oryzae or A. charticola + R. oryzae compared to control after 7 days of fermentation, however, the bacteria were not different between A. charticola-fermented cassava pulp and control. Lactic acid bacteria (LAB) were higher in A. charticola- and R. oryzae fermented cassava pulp than those in control, however, no difference of LAB was observed between A. charticola + R. oryzae-fermented cassava pulp and control. In conclusion, A. charticola exhibited antibacterial, antifungal and antioxidant activity, gastrointestinal persistence and fermentative capacity that may be beneficial for poultry industry. PMID- 26839500 TI - Four New Species of Amanita in Inje County, Korea. AB - Amanita (Agaricales, Basidiomycota) is one of the most well-known genera composed of poisonous mushrooms. This genus of almost 500 species is distributed worldwide. Approximately 240 macrofungi were collected through an ongoing survey of indigenous fungi of Mt. Jeombong in Inje County, Korea in 2014. Among these specimens, 25 were identified as members of Amanita using macroscopic features. Specimens were identified to the species level by microscopic features and molecular sequence analyses of the internal transcribed spacer and large subunit of nuclear ribosomal RNA. We molecularly identified 13 Amanita species, with seven species matching previously recorded species, four species (A. caesareoides, A. griseoturcosa, A. imazekii, and A. sepiacea) new to Korea, and two unknown species. PMID- 26839502 TI - The Effects of Different Substrates on the Growth, Yield, and Nutritional Composition of Two Oyster Mushrooms (Pleurotus ostreatus and Pleurotus cystidiosus). AB - The study was conducted to compare the effects of different agro-wastes on the growth, yield, and nutritional composition of oyster mushrooms Pleurotus ostreatus (PO) and Pleurotus cystidiosus (PC). Seven substrate formulas including sawdust (SD), corncob (CC), sugarcane bagasse (SB) alone and in combination of 80 : 20, 50 : 50 ratio between SD and CC, SD and SB were investigated. The results indicated that different substrate formulas gave a significant difference in total colonization period, characteristics of fruiting bodies, yield, biological efficiency (BE), nutritional composition and mineral contents of two oyster mushrooms PO and PC. The results showed that increasing CC and SB reduced C/N ratio, and enhanced some mineral contents (Ca, P, and Mg) of substrate formulas. The increased amount of CC and SB of substrate formulas enhanced protein, ash, mineral contents (Ca, K, Mg, Mn, and Zn) of fruiting bodies of both mushrooms. Substrates with 100% CC and 100% SB were the most suitable substrate formulas for cultivation of oyster mushrooms PO and PC in which they gave the highest values of cap diameter, stipe thickness, mushroom weight, yield, BE, protein, fiber, ash, mineral content (Ca, K, and Mg) and short stipe length. However, substrate formula 100% CC gave the slowest time for the first harvest of both mushrooms PO and PC (46.02 days and 64.24 days, respectively). It is also found that the C/N ratio of substrate formulas has close correlation with total colonization period, mushroom weight, yield, BE and protein content of mushroom PO and PC. PMID- 26839503 TI - Phylogenetic Diversity and Antifungal Activity of Endophytic Fungi Associated with Tephrosia purpurea. AB - Sixty-one endophytic fungus strains with different colony morphologies were isolated from the leaves, stems and roots of Tephrosia purpurea with colonization rates of 66.95%, 37.50%, and 26.92%, respectively. Based on internal transcribed spacer sequence analysis, 61 isolates were classified into 16 genera belonging to 3 classes under the phylum Ascomycota. Of the 61 isolates, 6 (9.84%) exhibited antifungal activity against one or more indicator plant pathogenic fungi according to the dual culture test. Isolate TPL25 had the broadest antifungal spectrum of activity, and isolate TPL35 was active against 5 plant pathogenic fungi. Furthermore, culture filtrates of TPL25 and TPL35 exhibited greater than 80% growth inhibition against Sclerotinia sclerotiorum. We conclude that the endophytic fungal strains TPL25 and TPL35 are promising sources of bioactive compounds. PMID- 26839504 TI - Growth Characteristics of Rhizophagus clarus Strains and Their Effects on the Growth of Host Plants. AB - Arbuscular mycorrhizal fungi (AMF) are ubiquitous in the rhizosphere and form symbiotic relationships with most terrestrial plant roots. In this study, four strains of Rhizophagus clarus were cultured and variations in their growth characteristics owing to functional diversity and resultant effects on host plant were investigated. Growth characteristics of the studied R. clarus strains varied significantly, suggesting that AMF retain high genetic variability at the intraspecies level despite asexual lineage. Furthermore, host plant growth response to the R. clarus strains showed that genetic variability in AMF could cause significant differences in the growth of the host plant, which prefers particular genetic types of fungal strains. These results suggest that the intraspecific genetic diversity of AMF could be result of similar selective pressure and may be expressed at a functional level. PMID- 26839505 TI - Differential Modulation of Lipopolysaccharide-Induced Inflammatory Cytokine Production by and Antioxidant Activity of Fomentariol in RAW264.7 Cells. AB - Medicinal mushrooms have been used worldwide to treat cancer and modulate the immune system. Over the last several years, there has been increasing interest in isolating bioactive compounds from medicinal mushrooms and evaluating their health beneficial effects. Fomes fomentarius is used in traditional oriental medicine and is known to possess antioxidant, anti-inflammatory, antidiabetic, and antitumor effects. In the present study, we isolated fomentariol from Fomes fomentarius and investigated its anti-inflammatory effect in murine macrophages (RAW264.7 cells) stimulated with lipopolysaccharides. Fomentariol inhibited the production of nitric oxide and intracellular reactive oxygen species triggered by lipopolysaccharides. Interestingly, fomentariol differentially regulated cytokine production triggered by lipopolysaccharides. Fomentariol effectively suppressed the production of interleukin-1beta and interleukin-6 but not tumor necrosis factor-alpha. The inhibitory effect of fomentariol against nitric oxide, interleukin-1beta, and interleukin-6 production was possibly mediated by downregulation of the extracellular signal-regulated kinase signaling pathway. Taken together, our results suggest that fomentariol differentially modulated inflammatory responses triggered by lipopolysaccharides in macrophages and is one of the bioactive compounds that mediate the physiological effects of Fomes fomentarius. PMID- 26839506 TI - Yeast Associated with the Ambrosia Beetle, Platypus koryoensis, the Pest of Oak Trees in Korea. AB - Oak tree death caused by symbiosis of an ambrosia beetle, Platypus koryoensis, and an ophiostomatoid filamentous fungus, Raffaelea quercus-mongolicae, has been a nationwide problem in Korea since 2004. In this study, we surveyed the yeast species associated with P. koryoensis to better understand the diversity of fungal associates of the beetle pest. In 2009, a total of 195 yeast isolates were sampled from larvae and adult beetles (female and male) of P. koryoensis in Cheonan, Goyang, and Paju; 8 species were identified by based on their morphological, biochemical and molecular analyses. Meyerozyma guilliermondii and Candida kashinagacola were found to be the two dominant species. Among the 8 species, Candida homilentoma was a newly recorded yeast species in Korea, and thus, its mycological characteristics were described. The P. koryoensis symbiont R. quercusmongolicae did not show extracelluar CM-cellulase, xylanase and avicelase activity that are responsible for degradation of wood structure; however, C. kashinagacola and M. guilliermondii did show the three extracellular enzymatic activities. Extracelluar CM-cellulase activity was also found in Ambrosiozyma sp., C. homilentoma, C. kashinagacola, and Candida sp. Extracelluar pectinase activity was detected in Ambrosiozyma sp., C. homilentoma, Candida sp., and M. guilliermondii. All the 8 yeast species displayed compatible relationships with R. quercus-mongolicae when they were co-cultivated on yeast extract-malt extract plates. Overall, our results demonstrated that P. koryoensis carries the yeast species as a symbiotic fungal associate. This is first report of yeast diversity associated with P. koryoensis. PMID- 26839507 TI - Assessment of Palm Press Fibre and Sawdust-Based Substrate Formulas for Efficient Carpophore Production of Lentinus squarrosulus (Mont.) Singer. AB - Development of efficient substrate formulas to improve yield and shorten production time is one of the prerequisites for commercial cultivation of edible mushrooms. In this study, fifteen substrate formulas consisting of varying ratios of palm press fibre (PPF), mahogany sawdust (MS), Gmelina sawdust, wheat bran (WB), and fixed proportions of 1% calcium carbonate (CaCO3) and 1% sucrose were assessed for efficient Lentinus squarrosulus production. Proximate compositions of mushrooms produced on the different substrate formulas were also analysed and compared. Substrate formulations containing 85% PPF, 13% WB, 1% CaCO3, and 1% sucrose were found to produce the highest carpophore yield, biological efficiency and size (206.5 g/kg, 61.96%, and 7.26 g, respectively). Days to production (first harvest) tended to increase with an increase in the amount of WB in the substrate formulas, except for PPF based formulas. The addition of WB in amounts equivalent to 8~18% in substrate formulas containing 80~90% PPF resulted in a decrease in the time to first harvest by an average of 17.7 days compared to 80~90% MS with similar treatment. Nutritional content of mushrooms was affected by the different substrate formulas. Protein content was high for mushrooms produced on formulas containing PPF as the basal substrate. Thus, formulas comprising PPF, WB, CaCO3, and sucrose at 85% : 13% : 1% : 1%) respectively could be explored as starter basal ingredients for efficient large scale production of L. squarrosulus. PMID- 26839508 TI - Molecular Identification of Mycorrhizae of Cymbidium kanran (Orchidaceae) on Jeju Island, Korea. AB - A fungal internal transcribed spacer region was used to identify the mycorrhizae of Cymbidium kanran. The family Russulaceae was found to be the most frequently occurring group in both root and soil samples. In phylogenetic analyses, the majority of the Russulaceae clones were clustered with Russula brevipes and R. cyanoxantha. Therefore, C. kanran may form symbiotic relationships with the genus Russula. PMID- 26839509 TI - A Clinicopathological Analysis of Soft Tissue Sarcoma with Telangiectatic Changes. AB - Background. Soft tissue sarcoma with a hemorrhagic component that cannot be easily diagnosed by needle biopsy is defined here as soft tissue sarcoma with telangiectatic changes (STST). Methods. We retrospectively reviewed clinicopathological data of STST from 14 out of 784 patients (prevalence: 1.8%) with soft tissue sarcoma. Results. Tumors were found mostly in the lower leg. Histological diagnoses were undifferentiated pleomorphic sarcoma (n = 5), synovial sarcoma (n = 5), epithelioid sarcoma (n = 2), and malignant peripheral nerve sheath tumor and fibrosarcoma (n = 1). No history of trauma to the tumor site was recorded in any patient. Needle aspiration transiently reduced the tumor volume, but subsequent recovery of tumor size was observed in all cases. Out of 14 patients, 9 presented with a painful mass. MRI characteristics included intratumoral nodules (64.3%). The local recurrence rate was 14.3%, and the 2-year event-free survival rate was poorer (50%) than that of most sarcomas. Conclusions. STST is unique in its clinicopathological presentation. Painful hematomas without a trauma history, intratumoral nodules within a large hemorrhagic component, and subsequent recovery of tumor size after aspiration are indicative of the presence of STST. PMID- 26839510 TI - Factors associated with patient visits to the emergency department for asthma therapy in Pakistan. AB - BACKGROUND: Acute asthma is a chronic condition affecting people of all ages around the world and hence, is one of the leading causes of emergency department (ED) visits and hospital admissions globally. Most of them are related to poor patient practices and a weak healthcare system. The aim of our study was to assess the reasons for the increased usage of the ED by asthmatic patients in Pakistan. METHODS: A cross-sectional study was conducted on 600 asthmatic patients reporting to the ED of Civil Hospital Karachi over a 6-month period. The consenting patients were given a questionnaire to fill and the following data was collected: demographic information, duration of the disease, medications prescribed the, frequency of and reasons for outpatient clinic and ED visits for issues related to asthma. RESULT: According to our results most of the participants visited the ED to obtain a nebulized bronchodilator (90 %) or oxygen (79.5 %). Moreover, 44.8 % of the people visited the ED to get treatment without any delay and 24.0 % considered that the severity of asthma does not allow the patient to wait for clinic visits. Strikingly, 92.8 % claimed that inhaled corticosteroid therapy treatment should be stopped when patients feel better. Irregular follow ups with clinics, low education about asthma and an education level higher than a Bachelors degree were the most important factors associated with three or more ED visits per year, p values = 0.0289, 0.0110 and 0.0150 respectively. CONCLUSION: This study identifies several preventable risk factors responsible for recurrent visits to the ED by asthmatic patients in Pakistan. PMID- 26839511 TI - A retrospective study of long-term treatment outcomes for reduced vocal intensity in hypokinetic dysarthria. AB - BACKGROUND: Reduced vocal intensity is a core impairment of hypokinetic dysarthria in Parkinson's disease (PD). Speech treatments have been developed to rehabilitate the vocal subsystems underlying this impairment. Intensive treatment programs requiring high-intensity voice and speech exercises with clinician guided prompting and feedback have been established as effective for improving vocal function. Less is known, however, regarding long-term outcomes of clinical benefit in speakers with PD who receive these treatments. METHODS: A retrospective cohort design was utilized. Data from 78 patient files across a three year period were analyzed. All patients received a structured, intensive program of voice therapy focusing on speaking intent and loudness. The dependent variable for all analyses was vocal intensity in decibels (dBSPL). Vocal intensity during sustained vowel production, reading, and novel conversational speech was compared at pre-treatment, post-treatment, six month follow-up, and twelve month follow-up periods. RESULTS: Statistically significant increases in vocal intensity were found at post-treatment, 6 months, and 12 month follow-up periods with intensity gains ranging from 5 to 17 dB depending on speaking condition and measurement period. Significant treatment effects were found in all three speaking conditions. Effect sizes for all outcome measures were large, suggesting a strong degree of practical significance. CONCLUSIONS: Significant increases in vocal intensity measured at 6 and 12 moth follow-up periods suggested that the sample of patients maintained treatment benefit for up to a year. These findings are supported by outcome studies reporting treatment outcomes within a few months post-treatment, in addition to prior studies that have reported long-term outcome results. The positive treatment outcomes experienced by the PD cohort in this study are consistent with treatment responses subsequent to other treatment approaches which focus on high-intensity, clinician guided motor learning for voice and speech production in PD. Theories regarding the underlying neurophysiological response to treatment will be discussed. PMID- 26839512 TI - The forest as a classroom: preparing for mental health practice. AB - BACKGROUND: Positive effects of physical activity, health promotion and disease prevention, in treatment of mental illnesses are well documented. Mental health practice for nursing students highlights the important connection between physical activities and mental health. This study aims to examine the outcome from nursing students' participation using The forest as a classroom. Students' collaboration by problem solving, theoretical discussions and performance of activities in the forest serves as a repertoire of non-medical treatment strategies in mental health. METHODS: The forest as a classroom was evaluated by means of an ad-hoc questionnaire including both standardized and open-ended questions. Data was analyzed by means of descriptive statistics and content analysis. RESULTS: The results indicated enhanced knowledge about physical activity and its impact on mental health. However, the nursing students' experience challenge preserving theoretical exercises outdoor because sensory stimulation took attention away from learning. CONCLUSIONS: For nursing students it is essential to build a repertoire of treatment activities to care for patients having mental health problems. This kind of approach is supported by the students' learning in the forest. The pilot study highlights the importance of multiple methods of learning in nursing education. PMID- 26839514 TI - Nur77-mediated TRAF6 signalling protects against LPS-induced sepsis in mice. AB - BACKGROUND: Nur77, a key member of the NR4A receptor subfamily, is involved in the regulation of inflammation and immunity. However, the in vivo regulatory roles of Nur77 in sepsis and the mechanisms involved remains largely elusive. In this study, we used Nur77-deficient (Nur77(-/-)) mice and investigated the function of Nur77 in sepsis. FINDINGS: Compared to wild-type (Nur77(+/+)) mice, Nur77(-/-) mice are more susceptible to LPS-induced sepsis and acute liver inflammation. Mechanistically, we observed that Nur77 can interact with TRAF6, a crucial adaptor molecule in the Toll-like receptor-interleukin 1 receptor (TLR-IL 1R) signalling pathway, in in vivo mouse model of sepsis. The interaction may affect TRAF6 auto-ubiquitination, thereby inhibiting NF-kappaB activation and pro inflammatory cytokines production. CONCLUSIONS: These in vivo observations reveals an important protective role for Nur77 in LPS-induced sepsis through its regulation to TRAF6 signalling, and highlights the potential clinical application of Nur77 as a molecular target in prevention and/or treatment of sepsis. PMID- 26839513 TI - Quince peel polyphenolic extract blocks human colon adenocarcinoma LS174 cell growth and potentiates 5-fluorouracil efficacy. AB - BACKGROUND: Development of alternative cancer-specific drugs would be of paramount importance to overcome toxicity toward normal tissues and tumor resistance. Here, we investigated the potential anti-tumoral effect of peel (Peph) and pulp polyphenolic extracts from the Tunisian quince Cydonia oblonga Miller on both no-tumorigenic cells NIH 3T3 Fibroblasts and HEK 293 cells and human colon adenocarcinoma LS174 cells. METHODS: Cell proliferation and cytotoxicity were measured with MTT and LDH assays respectively. Cell cycle distribution and the apoptosis levels were assessed by flow cytometry. Intracellular reactive oxygen species (ROS) levels were determined using the fluorescent probe CM-H2DCFDA. Western blot was used to further characterize cell death and analyze the signaling pathways affected by Peph treatment. The expression level of VEGF-A was evaluated by real time quantitative PCR and further verified by quantifying the secreted cytokines by enzyme-linked immunosorbent assay. RESULTS: We found that Peph extract displayed the highest anti-proliferative effect specifically on LS174 cells. However, each Peph phenolic compound alone did not exhibit any anti-proliferative activity, suggesting a synergistic effect of phenolic molecules. Such effect was associated with a cell cycle arrest in the G1/S phase, a caspase-independent apoptosis and an increase of the ROS production. Peph extract inhibited the pro-survival signaling pathway NFkappaB and suppressed the expression of various cellular markers known to be involved in cell cycling (cyclin D1) and angiogenesis (Vascular Endothelial Growth Factor, VEGF). Interestingly, the combination Peph extract and 5-FU exerted synergistic inhibitory effect on cell viability. CONCLUSION: These data propose the quince Peph extract as a promising cost effective non toxic drug to employ alone or in combination with conventional anti colorectal cancer. Moreover, quince rich regimen may prevent the development and the progress of colon cancer. PMID- 26839515 TI - Secretome analysis of rice suspension-cultured cells infected by Xanthomonas oryzae pv.oryza (Xoo). AB - BACKGROUND: Rice bacterial blight (BB) caused by Xanthomonas oryzae pv.oryzae (Xoo) is one of the most devastating bacterial diseases in rice-growing regions worldwide. The rice-Xoo interaction is a classical model for studying the interaction between plants and pathogens. Secreted proteins play important roles in plant-bacterial interactions, but are poorly studied in the rice-Xoo system. Rice cv. Nipponbare is highly susceptible to Xoo. Here, we used two-dimensional difference gel electrophoresis (2D-DIGE) coupled with MALDI-TOF/TOF mass spectrometry (MS), to investigate secreted proteins in Nipponbare embryo cell suspension culture infected by Xoo. RESULTS: A total of 32 protein spots changed significantly (p < 0.05) by more than 1.5 fold in gel intensity after Xoo inoculation, and were identified by MS. They represent protein products of 11 unique genes, seven from rice and four from Xoo. Of the rice proteins, six up regulated proteins are involved in cell wall modification, the TCA cycle, glycolysis and redox, while a down-regulated protein, CHIT16, is involved in plant defense. Quantitative Real-Time PCR showed that transcript levels were not correlated with secreted protein levels. Of the Xoo proteins, three of them were possibly located in the extracellular space as shown by transient expression assays in rice protoplasts. Two of the Xoo proteins were previously reported to be likely involved in pathogenicity, and the third gene, Xoo3654, is likely a negative regulator of Xoo virulence as its overexpression reduced Xoo pathogenicity in our study. CONCLUSION: Among the secreted proteins that responded to Xoo inoculation, we identified rice proteins involved in cell defense and Xoo proteins involved in pathogenicity. Our study also showed that Xoo3654 (X2) protein is likely a novel negative regulator of Xoo virulence. These results not only help us better understand the interaction between susceptible rice and Xoo, but also serve as a reference for studying the interaction between other plants and their pathogens. PMID- 26839516 TI - Vectors for Genetically-Encoded Tags for Electron Microscopy Contrast in Drosophila. AB - BACKGROUND: One of the most notable recent advances in electron microscopy (EM) was the development of genetically-encoded EM tags, including the fluorescent flavoprotein Mini-SOG (Mini-Singlet Oxygen Generator). Mini-SOG generates good EM contrast, thus providing a viable alternative to technically-demanding methods such as immuno-electron microcopy (immuno-EM). Based on the Mini-SOG technology, in this paper, we describe the construction, validation and optimization of a series of vectors which allow expression of Mini-SOG in the Drosophila melanogaster genetic model system. FINDINGS: We constructed a Mini-SOG tag that has been codon-optimized for expression in Drosophila (DMS tag) using PCR mediated gene assembly. The photo-oxidation reaction triggered by DMS was then tested using these vectors in Drosophila cell lines. DMS tag did not affect the subcellular localization of the proteins we tested. More importantly, we demonstrated the utility of the DMS tag for EM in Drosophila by showing that it can produce robust photo-oxidation reactions in the presence of blue light and the substrate DAB; the resultant electron micrographs contain electron-dense regions corresponding to the protein of interest. The vectors we generated allow protein tagging at both termini, for constitutive and inducible protein expression, as well as the generation of transgenic lines by P-element transformation. CONCLUSIONS: We demonstrated the feasibility of Mini-SOG tagging in Drosophila. The constructed vectors will no doubt be a useful molecular tool for genetic tagging to facilitate high-resolution localization of proteins in Drosophila by electron microscopy. PMID- 26839517 TI - Sipuleucel-T for the Treatment of Patients With Metastatic Castrate-resistant Prostate Cancer: Considerations for Clinical Practice. AB - Sipuleucel-T treatment is associated with a significant and consistent survival benefit in patients with metastatic castrate-resistant prostate cancer. Most adverse events are infusion related, manageable, and of short duration. Early screening and diagnosis of metastatic disease is important, as the greatest survival benefit may occur in patients with a lower disease burden. The short duration of sipuleucel-T treatment facilitates the use of subsequent therapies. Sipuleucel-T is now being used in the clinic for patients with a lower disease burden. We present our own experience with the use of sipuleucel-T in the setting of a large urology practice. PMID- 26839519 TI - Smoking: Its Impact on Urologic Health. AB - Tobacco use remains the single largest preventable cause of disease and premature death in the United States, and smoking is a leading cause of cancer and death from cancer. There is also evidence that smoking is associated with several urologic diseases. Urologists have a unique opportunity to help our patients lead healthy lifestyles, which includes ending their dependence on nicotine and tobacco. This article points out the various urologic conditions associated with smoking and tobacco use with the intention of providing physicians and patients with knowledge and education regarding this connection. PMID- 26839518 TI - Fertility Preservation Options for Men and Women With Cancer. AB - Approximately 0.2% of Americans aged 20 to 39 years are childhood cancer survivors. Advances in cancer detection and therapy have greatly improved survival rates for young cancer patients; however, treatment of childhood cancers can adversely impact reproductive function. Many cancer patients report a strong desire to be informed of existing options for fertility preservation and future reproduction prior to initiation of gonadotoxic cancer therapies, including surgery, chemotherapy, and radiotherapy. This article discusses, in detail, the effects of cancer treatment on fertility in men and women, and outlines both current and experimental methods of fertility preservation among cancer patients. PMID- 26839520 TI - Can Serum Testosterone Be Used as a Marker of Overall Health? AB - Low serum testosterone has been associated with obesity, type 2 diabetes, metabolic syndrome, and atherosclerosis. Individuals with these comorbidities are at increased risk of premature death and other adverse health effects. Clinical data portend low testosterone as a risk factor for developing these conditions which are supported by the hypogonadal-obesity-adipocytokine hypothesis. The authors support comprehensive evaluation for these comorbid conditions in men found to have low serum testosterone. PMID- 26839521 TI - The 4Kscore(r) Test Reduces Prostate Biopsy Rates in Community and Academic Urology Practices. AB - There is significant concern regarding prostate cancer screening because of the potential for overdiagnosis and overtreatment of men who are discovered to have abnormal prostate specific antigen (PSA) levels and/or digital rectal examination (DRE) results. The 4Kscore(r) Test (OPKO Diagnostics, LLC) is a blood test that utilizes four kallikrein levels plus clinical information in an algorithm to calculate an individual's percentage risk (< 1% to > 95%) for aggressive prostate cancer (Gleason score >= 7) on prostate biopsy. The 4Kscore Test, as a follow-up test after abnormal PSA and/or DRE test results, has been shown to improve the specificity for predicting the risk of aggressive prostate cancer and reduce unnecessary prostate biopsies. A clinical utility study was conducted to assess the influence of the 4Kscore Test on the decision to perform prostate biopsies in men referred to urologists for abnormal PSA and/or DRE results. The study population included 611 patients seen by 35 academic and community urologists in the United States. Urologists ordered the 4Kscore Test as part of their assessment of men referred for abnormal PSA and/or DRE test results. Results for the patients were stratified into low risk (< 7.5%), intermediate risk (7.5% 19.9%), and high risk (>= 20%) for aggressive prostate cancer. The 4Kscore Test results influenced biopsy decisions in 88.7% of the men. Performing the 4Kscore Test resulted in a 64.6% reduction in prostate biopsies in patients; the actual percentage of cases not proceeding to biopsy were 94.0%, 52.9%, and 19.0% for men who had low-, intermediate-, and high-risk 4Kscore Test results, respectively. A higher 4Kscore Test was associated with greater likelihood of having a prostate biopsy (P < 0.001). Among the 171 patients who had a biopsy, the 4Kscore risk category is strongly associated with biopsy pathology. The 4Kscore Test, as a follow-up test for an abnormal PSA and/or DRE results, significantly influenced the physician and patient shared decision in clinical practice, which led to a reduction in prostate biopsies while increasing the probability of detecting aggressive cancer. PMID- 26839522 TI - Effectiveness of Antegrade Access in Bladder Tumors With Inaccessible Urethra. AB - Inaccessible urethra with no retrograde endoscopic access due to multiple/diffuse strictures or multiple urethrocutaneous fistulas with acute urinary retention due to posturethral instrumentation (transurethral resection of bladder tumor [TURBT], or TURBT with transurethral resection of the prostate [TURP]), is a rare entity. Management of such a case with a bladder tumor for TURBT/surveillance cystoscopy poses a great challenge. The authors present 12 cases of bladder tumor with inaccessible urethra, 10 cases due to multiple strictures (post-TURBT and/or TURP), and 2 cases due to urethrocutaneous fistulas (post-TURBT), who presented to our emergency department with acute urinary retention. Emergent suprapubic catheterization was used as a temporary treatment method. PMID- 26839523 TI - Acromegaly Presenting as Erectile Dysfunction: Case Reports and Review of the Literature. AB - Erectile dysfunction (ED) is a common yet complex condition. The authors report two cases of acromegaly presenting with ED and hypogonadotropic hypogonadism. Surgical cure of the acromegaly was associated with either an improvement or resolution of hypogonadotropic hypogonadism-associated ED. Active acromegaly should be considered in the differential diagnosis of ED presenting with supporting clinical features, particularly hypogonadotropic hypogonadism. PMID- 26839524 TI - Sorafenib-induced Scrotal Eczema. AB - Sorafenib is an orally active, small-molecule multikinase inhibitor that blocks tumor cell proliferation and angiogenesis. Studies have shown that it is a highly potent, selective inhibitor of vascular endothelial growth factor receptors 2 and 3, platelet-derived growth factor-beta, RAF, FLT-3, and c-Kit. This drug was recently approved for the treatment of metastatic renal cell carcinoma and hepatocellular carcinoma. We report a case of a patient treated with sorafenib for metastatic renal cell carcinoma who developed scrotal eczema. PMID- 26839525 TI - Gender Affirmation and Body Modification Among Transgender Persons in Bogota, Colombia. AB - This paper examined structural, social, and personal characteristics that shape the processes of gender affirmation and body modification among transgender persons (assigned male at birth) in Bogota, Colombia. Qualitative data from life history interviews (N=14) and a focus group (N=11) explored research questions concerning the ways in which the internal psychological and external contextual processes influence individuals' decisions and behaviors concerning hormonal treatment, injections, or surgery. Research questions concerning practices and consequences of treatment performed without medical supervision were addressed through qualitative data, as well as quantitative data from 58 transgender participants. Findings indicated variation in ways participants conceptualized gender (e.g., binary or fluid), but an increased feminine presentation was a strong personal desire expressed by many and often encouraged by romantic partners and transgender friends. Transgender individuals within participants' social networks were frequently instrumental not only in providing information about hormones and contouring injections, but also in carrying out procedures sometimes with negative consequences. Body modification procedures occurred primarily outside the health care system, due to limited access to or awareness of medical care, societal stigma, social norms within the transgender community, and personal decision-making. Public health approaches to protect the health of transgender persons undergoing body modification were suggested. PMID- 26839526 TI - Efficient one-pot synthesis, molecular docking and in silico ADME prediction of bis-(4-hydroxycoumarin-3-yl) methane derivatives as antileishmanial agents. AB - Bis-(4-hydroxycoumarin-3-yl) methane derivatives 3(a-l) were synthesized from 4 hydroxycoumarin and substituted aromatic aldehydes using succinimide-N-sulfonic acid as catalyst and evaluated for their in vitro antileishmanial activity against promastigotes form of Leishmania donovani. Compounds 3a (IC50= 155 MUg/mL), 3g (IC50= 157.5 MUg/mL) and 3l (IC50= 150 MUg/mL) were shown significant antileishmanial activity when compared with standard sodium stibogluconate (IC50= 490 MUg/mL). Also, synthesized compounds 3(a-l) did not show cytotoxicity against HeLa cell line upto tested concentrations. Further, molecular docking study against Adenine phosphoribosyltransferase of Leishmania donovani showed good binding interactions. ADME properties were analyzed and showed good oral drug candidate like properties. The synthesized compounds were also shown good drug likeness and drug score values when compared with drugs currently used in therapy. The present study has helped us in identifying a new lead that could be exploited as a potential antileishmanial agent. PMID- 26839527 TI - Sesamol ameliorates hypotension by modulating cytokines and PPAR-gamma in systemic inflammatory response. AB - Sepsis is one of the major causes of death reported in intensive care units. Acute kidney injury (AKI) and hypotension are important in the pathogenesis and mortality of systemic inflammatory response (SIR). Sesamol delays mortality in sepsis; however, its effects on AKI and hypotension and the role of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) activation have not been established. We investigated the effect of sesamol on SIR in cecal ligation and puncture (CLP)-induced acute kidney injury and lipopolysaccharide (LPS)-induced hypotension in rats. Sesamol was subcutaneously injected 1 h after SIR. Renal function (BUN and CRE) and proinflammatory mediators interleukin (IL)-1beta and IL-6 were increased after CLP. Tumor necrosis factor (TNF)-alpha, IL-1beta, IL 10, and nitrite production were significantly increased 6 h after LPS-induced hypotension (mean arterial pressure was significantly decreased). Sesamol significantly inhibited BUN, CRE, IL-1beta, IL-6, and nitrite after CLP-induced acute renal injury. In addition, sesamol increased mean arterial pressure and IL 10, inhibited TNF-alpha and IL-1beta, but did not affect nitrite production in LPS-induced hypotension. Sesamol increased PPAR-gamma in the leucocytes and peritoneal macrophages in LPS-induced SIR. We conclude that sesamol regulates leucocyte and macrophage PPAR-gamma-associated systemic cytokines expression, thereby ameliorates acute kidney injury and hypotension in rats. PMID- 26839528 TI - Perceptions of harm from secondhand smoke exposure among U.S. adults, 2009-2010. AB - BACKGROUND: Exposure to secondhand smoke (SHS) causes significant disease and death. We assessed the prevalence and correlates of perceptions about the health harm of SHS among U.S. adults at the national and state level. METHODS: Data came from the 2009-2010 National Adult Tobacco Survey, a national landline and cellular telephone survey. Perceptions about the health harms of SHS were assessed as follows: 'not at all harmful', 'somewhat harmful', and 'very harmful'. Descriptive statistics were used to assess the prevalence of SHS harm perceptions by tobacco use and sociodemographic factors, including sex, age, race/ethnicity, education, marital status, annual household income, region, sexual orientation, children in the household, and smoke-free law coverage. Logistic regression was used to assess odds of perceiving SHS to be "very harmful" (vs. "not at all harmful" or "somewhat harmful"), adjusting for the aforementioned factors. RESULTS: Nationally, 64.5 % of adults perceived SHS as 'very harmful' (state range: 73.5 % [Utah] to 53.7 % [Kentucky]). By tobacco use, the perception that SHS is 'very harmful' was: 76.5 % among nonusers of tobacco; 62.1 % among noncombustible only users; 47.9 % among combustible only users; and 40.8 % among dual combustible and noncombustible users. Following adjustment, the perception that SHS was 'very harmful' was higher among females, non-Hispanic minorities and Hispanics, respondents living with children, and states with 100 % smoke-free law coverage. Among current tobacco users the odds of perceiving SHS to be 'very harmful' was lower in the Midwest than the West. CONCLUSIONS: Almost two-thirds of American adults perceive SHS as 'very harmful'; however, currently only half of all Americans are protected by comprehensive state or local smoke free laws. These findings underscore the importance of public education campaigns to increase awareness of SHS exposure harm and the benefits of smoke-free environments. Expanding comprehensive smoke-free laws could protect all Americans from SHS. PMID- 26839529 TI - ATIPS: Automatic Travel Itinerary Planning System for Domestic Areas. AB - Leisure travel has become a topic of great interest to Taiwanese residents in recent years. Most residents expect to be able to relax on a vacation during the holidays; however, the complicated procedure of travel itinerary planning is often discouraging and leads them to abandon the idea of traveling. In this paper, we design an automatic travel itinerary planning system for the domestic area (ATIPS) using an algorithm to automatically plan a domestic travel itinerary based on user intentions that allows users to minimize the process of trip planning. Simply by entering the travel time, the departure point, and the destination location, the system can automatically generate a travel itinerary. According to the results of the experiments, 70% of users were satisfied with the result of our system, and 82% of users were satisfied with the automatic user preference learning mechanism of ATIPS. Our algorithm also provides a framework for substituting modules or weights and offers a new method for travel planning. PMID- 26839530 TI - Analysis of Residual Dependencies of Independent Components Extracted from fMRI Data. AB - Independent component analysis (ICA) of functional magnetic resonance imaging (fMRI) data can be employed as an exploratory method. The lack in the ICA model of strong a priori assumptions about the signal or about the noise leads to difficult interpretations of the results. Moreover, the statistical independence of the components is only approximated. Residual dependencies among the components can reveal informative structure in the data. A major problem is related to model order selection, that is, the number of components to be extracted. Specifically, overestimation may lead to component splitting. In this work, a method based on hierarchical clustering of ICA applied to fMRI datasets is investigated. The clustering algorithm uses a metric based on the mutual information between the ICs. To estimate the similarity measure, a histogram based technique and one based on kernel density estimation are tested on simulated datasets. Simulations results indicate that the method could be used to cluster components related to the same task and resulting from a splitting process occurring at different model orders. Different performances of the similarity measures were found and discussed. Preliminary results on real data are reported and show that the method can group task related and transiently task related components. PMID- 26839531 TI - Self-Trained LMT for Semisupervised Learning. AB - The most important asset of semisupervised classification methods is the use of available unlabeled data combined with a clearly smaller set of labeled examples, so as to increase the classification accuracy compared with the default procedure of supervised methods, which on the other hand use only the labeled data during the training phase. Both the absence of automated mechanisms that produce labeled data and the high cost of needed human effort for completing the procedure of labelization in several scientific domains rise the need for semisupervised methods which counterbalance this phenomenon. In this work, a self-trained Logistic Model Trees (LMT) algorithm is presented, which combines the characteristics of Logistic Trees under the scenario of poor available labeled data. We performed an in depth comparison with other well-known semisupervised classification methods on standard benchmark datasets and we finally reached to the point that the presented technique had better accuracy in most cases. PMID- 26839532 TI - A Multiobjective Approach to Homography Estimation. AB - In several machine vision problems, a relevant issue is the estimation of homographies between two different perspectives that hold an extensive set of abnormal data. A method to find such estimation is the random sampling consensus (RANSAC); in this, the goal is to maximize the number of matching points given a permissible error (Pe), according to a candidate model. However, those objectives are in conflict: a low Pe value increases the accuracy of the model but degrades its generalization ability that refers to the number of matching points that tolerate noisy data, whereas a high Pe value improves the noise tolerance of the model but adversely drives the process to false detections. This work considers the estimation process as a multiobjective optimization problem that seeks to maximize the number of matching points whereas Pe is simultaneously minimized. In order to solve the multiobjective formulation, two different evolutionary algorithms have been explored: the Nondominated Sorting Genetic Algorithm II (NSGA-II) and the Nondominated Sorting Differential Evolution (NSDE). Results considering acknowledged quality measures among original and transformed images over a well-known image benchmark show superior performance of the proposal than Random Sample Consensus algorithm. PMID- 26839533 TI - Improved Ant Colony Clustering Algorithm and Its Performance Study. AB - Clustering analysis is used in many disciplines and applications; it is an important tool that descriptively identifies homogeneous groups of objects based on attribute values. The ant colony clustering algorithm is a swarm-intelligent method used for clustering problems that is inspired by the behavior of ant colonies that cluster their corpses and sort their larvae. A new abstraction ant colony clustering algorithm using a data combination mechanism is proposed to improve the computational efficiency and accuracy of the ant colony clustering algorithm. The abstraction ant colony clustering algorithm is used to cluster benchmark problems, and its performance is compared with the ant colony clustering algorithm and other methods used in existing literature. Based on similar computational difficulties and complexities, the results show that the abstraction ant colony clustering algorithm produces results that are not only more accurate but also more efficiently determined than the ant colony clustering algorithm and the other methods. Thus, the abstraction ant colony clustering algorithm can be used for efficient multivariate data clustering. PMID- 26839534 TI - Cryoglobulinaemia in Egyptian Patients with Extrahepatic Cutaneous Manifestations of Chronic Hepatitis C Virus Infection. AB - Background. Hepatitis C is a global major health problem with extremely variable extrahepatic manifestations. Mixed cryoglobulinaemia (MC) shows a striking association with hepatitis C virus (HCV) infection, and it is sometimes asymptomatic. The skin is a frequently involved target organ in MC. Objective. To investigate the prevalence of cryoglobulinaemia in a sample of Egyptian patients with cutaneous manifestations of chronic HCV infection and to correlate its presence with clinical criteria and liver function tests. Methods. One hundred and eighteen patients with skin manifestations of chronic compensated hepatitis C were included. Venous blood was tested for liver function tests and serum cryoglobulins. Results. Twelve patients (10.169%) were positive for serum cryoglobulins (2 with pruritus, 4 with vasculitic lesions, 3 with livedo reticularis, one with oral lichen, one with chronic urticaria, and another with Schamberg's disease). Vasculitic lesions and livedo reticularis of the legs showed higher prevalence in cryoglobulin-positive than in cryoglobulin-negative patients. Presence of serum cryoglobulins did not relate to patients' demographic or laboratory findings. Conclusions. Fortunately, MC is not markedly prevalent among Egyptians with cutaneous lesions of chronic hepatitis C, and cryopositivity was commonly, but not exclusively, detected with cutaneous vasculitis and livedo reticularis. Laboratory testing for cryoglobulins in every HCV patient is advisable for earlier MC detection and management. PMID- 26839535 TI - CD44, Sonic Hedgehog, and Gli1 Expression Are Prognostic Biomarkers in Gastric Cancer Patients after Radical Resection. AB - Aim. CD44 and Sonic Hedgehog (Shh) signaling are important for gastric cancer (GC). However, the clinical impact, survival, and recurrence outcome of CD44, Shh, and Gli1 expressions in GC patients following radical resection have not been elucidated. Patients and Methods. CD44, Shh, and Gli1 protein levels were quantified by immunohistochemistry (IHC). The association between CD44, Shh, and Gli1 expression and clinicopathological features or prognosis of GC patients was determined. The biomarker risk score was calculated by the IHC staining score of CD44, Shh, and Gli1 protein. Results. The IHC positive staining of CD44, Shh, and Gli1 proteins was correlated with larger tumour size, worse gross type and histological type, and advanced TNM stage, which also predicted shorter overall survival (OS) and disease-free survival (DFS) after radical resection. Multivariate analysis indicated the Gli1 protein and Gli1, CD44 proteins were predictive biomarkers for OS and DFS, respectively. If biomarker risk score was taken into analysis, it was the independent prognostic factor for OS and DFS. Conclusions. CD44 and Shh signaling are important biomarkers for tumour aggressiveness, survival, and recurrence in GC. PMID- 26839536 TI - DUOX2 Expression Is Increased in Barrett Esophagus and Cancerous Tissues of Stomach and Colon. AB - Aim. To detect the expression of dual oxidase (DUOX) 2 in Barrett esophagus, gastric cancer, and colorectal cancer (CRC). Materials and Methods. The endoscopic biopsies were collected from patients with Barrett esophagus, while the curative resection tissues were obtained from patients with gastric cancer, CRC, or hepatic carcinoma. The DUOX2 protein and mRNA levels were detected with immunohistochemistry (IHC) and real-time quantitative PCR (qPCR). The correlation of DUOX2 expression with clinicopathological parameters of tumors was identified. Results. Low levels of DUOX2 mRNA were detected in Barrett esophagus and the adjacent normal tissues, and there was no difference between these two groups. DUOX2 protein was found in Barrett esophagus and undetectable in the normal epithelium. The DUOX2 mRNA and protein levels in the gastric cancer and CRC were increased compared to the adjacent nonmalignant tissues. The elevated DUOX2 in the gastric cancer was significantly associated with smoking history. In CRC tissues, the DUOX2 protein expression level in stages II-IV was significantly higher than that in stage I. In both hepatic carcinoma and the adjacent nonmalignant tissue, the DUOX2 was virtually undetectable. Conclusion. DUOX2 in Barrett esophagus, gastric cancer, and CRC may be involved in the tumorigenesis of these tissues. PMID- 26839537 TI - Dysfunctions in the Mature Dendritic Cells Are Associated with the Presence of Metastases of Colorectal Cancer in the Surrounding Lymph Nodes. AB - Dendritic cells play a key role in the antigen presentation and T cell activation. The aim of this study was a detailed analysis of the presence of mature dendritic cells (CD 83 positive) in colorectal cancer in correlation with selected clinicopathological parameters. The presence of mature dendritic cells (mDCs) was determined immunohistochemically using the anti-CD83 antibody. The morphometric analysis of the mDCs was performed in the normal colon wall adjacent to the cancerous tumor as well as in the front of the tumor and in the main mass of the cancerous tumor. Decrease in mDCs in the front and in the main tumor mass was observed. The increase in the number of mDCs in both of these locations was associated with the presence of metastases in the nearby lymph nodes (p < 0.05 and p < 0.01). Furthermore, the increase in the proportion of mDCs in the main tumor mass was associated with the presence of the invasion of tumor cells into the blood and lymph vessels (p < 0.01). The increase in the amount of mDCs in the cancerous tumor is associated with the invasiveness of the tumor and especially with the metastasis to the surrounding lymph nodes. PMID- 26839538 TI - Cholecystostomy as Bridge to Surgery and as Definitive Treatment or Acute Cholecystectomy in Patients with Acute Cholecystitis. AB - Purpose. Percutaneous cholecystostomy (PC) has increasingly been used as bridge to surgery as well as sole treatment for patients with acute cholecystitis (AC). The aim of the study was to assess the outcome after PC compared to acute cholecystectomy in patients with AC. Methods. A review of medical records was performed on all patients residing in Stockholm County treated for AC in the years 2003 and 2008. Results. In 2003 and 2008 altogether 799 and 833 patients were admitted for AC. The number of patients treated with PC was 21/799 (2.6%) in 2003 and 50/833 (6.0%) in 2008. The complication rate (Clavien-Dindo >= 2) was 4/71 (5.6%) after PC and 135/736 (18.3%) after acute cholecystectomy. Mean (standard deviation) hospital stay was 11.4 (10.5) days for patients treated with PC and 5.1 (4.3) days for patients undergoing acute cholecystectomy. After adjusting for age, gender, Charlson comorbidity index, and degree of cholecystitis, the hospital stay was significantly longer for patients treated with PC than for those undergoing acute cholecystectomy (P < 0.001) but the risk for intervention-related complications was found to be significantly lower (P = 0.001) in the PC group. Conclusion. PC can be performed with few serious complications, albeit with a longer hospital stay. PMID- 26839539 TI - Interventional Treatment of Abdominal Compartment Syndrome during Severe Acute Pancreatitis: Current Status and Historical Perspective. AB - Abdominal compartment syndrome (ACS) in patients with severe acute pancreatitis (SAP) is a marker of severe disease. It occurs as combination of inflammation of retroperitoneum, visceral edema, ascites, acute peripancreatic fluid collections, paralytic ileus, and aggressive fluid resuscitation. The frequency of ACS in SAP may be rising due to more aggressive fluid resuscitation, a trend towards conservative treatment, and attempts to use a minimally invasive approach. There remains uncertainty about the most appropriate surgical technique for the treatment of ACS in SAP. Some unresolved questions remain including medical treatment, indications, timing, and interventional techniques. This review will focus on interventional treatment of this serious condition. First line therapy is conservative treatment aiming to decrease IAP and to restore organ dysfunction. If nonoperative measures are not effective, early abdominal decompression is mandatory. Midline laparostomy seems to be method of choice. Since it carries significant morbidity we need randomized studies to establish firm advantages over other described techniques. After ACS resolves efforts should be made to achieve early primary fascia closure. Additional data are necessary to resolve uncertainties regarding ideal timing and indication for operative treatment. PMID- 26839540 TI - Probiotics and Alcoholic Liver Disease: Treatment and Potential Mechanisms. AB - Despite extensive research, alcohol remains one of the most common causes of liver disease in the United States. Alcoholic liver disease (ALD) encompasses a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Although many agents and approaches have been tested in patients with ALD and in animals with experimental ALD in the past, there is still no FDA (Food and Drug Administration) approved therapy for any stage of ALD. With the increasing recognition of the importance of gut microbiota in the onset and development of a variety of diseases, the potential use of probiotics in ALD is receiving increasing investigative and clinical attention. In this review, we summarize recent studies on probiotic intervention in the prevention and treatment of ALD in experimental animal models and patients. Potential mechanisms underlying the probiotic function are also discussed. PMID- 26839541 TI - Correlation between Histological Activity and Endoscopic, Clinical, and Serologic Activities in Patients with Ulcerative Colitis. AB - Objectives. Recent studies suggest that histological healing is a treatment goal in ulcerative colitis (UC). We aimed to evaluate the correlation between histological activity and clinical, endoscopic, and serologic activities in patients with UC. Methods. We retrospectively reviewed medical records from patients with UC who underwent colonoscopy or sigmoidoscopy with biopsies. The Mayo endoscopic subscore was used to assess endoscopic activity. Biopsy specimens were reviewed by two blinded pathologists and scored using the Geboes scoring system. Results. We analyzed 154 biopsy specimens from 82 patients with UC. Histological scores exhibited strong correlation with endoscopic subscores (Spearman's rank correlation coefficient r = 0.774, p < 0.001) and moderate correlation with C-reactive protein levels (r = 0.422, p < 0.001) and partial Mayo scores (r = 0.403, p < 0.001). Active histological inflammation (Geboes score >= 3.1) was observed in 6% (2 of 33) of the endoscopically normal mucosa samples, 66% (19 of 29) of mild disease samples, and 98% (90 of 92) of moderate to-severe disease samples. Conclusions. Histological activity was closely correlated with the endoscopic, clinical, and serologic UC activities. However, several patients with mild or normal endoscopic findings exhibited histological evidence of inflammation. Therefore, histological assessment may be helpful in evaluating treatment outcomes and determining follow-up strategies. PMID- 26839542 TI - Second-Line Irinotecan, Leucovorin, and 5-Fluorouracil for Gastric Cancer Patients after Failed Docetaxel and S-1. AB - Background. This retrospective study aimed to assess the efficacy and toxicities of second-line chemotherapy with irinotecan, leucovorin, and 5-fluorouracil (5 FU) in metastatic gastric cancer (MGC) patients previously treated with docetaxel and S-1 with or without oxaliplatin (DS/DOS). Patients and Methods. We reviewed the data of patients who had previously been treated with first-line DS/DOS and received biweekly irinotecan-based chemotherapy (FOLFIRI/IFL) between October 2004 and November 2011. Results. A total of 209 cycles were administered to 35 patients, with a median of 4 (range, 1-22) cycles each. The overall response rate in 29 response-assessable patients was 17.2%, including 2 complete and 3 partial responses. The median progression-free and overall survivals were 3.81 (95% confidence interval [CI], 1.82-5.80) months and 6.24 (95% CI, 1.44-11.04) months, respectively. The major grade 3/4 toxicity was neutropenia (8.6%). Conclusion. FOLFIRI/IFL chemotherapy showed modest antitumour activity and tolerable toxicities in DS/DOS-treated MGC patients. PMID- 26839543 TI - Nurse Participation in Colonoscopy Observation versus the Colonoscopist Alone for Polyp and Adenoma Detection: A Meta-Analysis of Randomized, Controlled Trials. AB - The role of nurse participation (NP) in colonoscopy observation for polyp and adenoma detection is unclear. This study aimed to evaluate whether nurse participation can improve polyp and adenoma detection. Patients and Methods. The PUBMED, EMBASE, and Cochrane Library databases were searched for randomized controlled trials (RCTs) published in English. The outcome measurements included (1) the polyp and adenoma detection rate (PDR and ADR); (2) the advanced lesions detection rate; and (3) the mean polyp and adenoma detection rate per colonoscopy. Results. Three RCTs with a total of 1676 patients were included. The pooled data showed a significantly higher ADR in the NP group than colonoscopist alone (CA) (45.7% versus 39.3%; RR 1.16; 95% CI, 1.04-1.30). And it showed no significant difference in the PDR and advanced lesions detection rate between the two groups (RR: 1.14, 95% CI: 0.95-1.37; RR: 1.35, 95% CI: 0.91-2.00; resp.). Conclusions. Nurse participation during a colonoscopy can improve the ADR, whereas no benefit for the PDR and advanced lesions detection rate was observed. All RCTs included in the meta-analysis had high risk of bias. Thus, there is a need for new research that uses sound methodology to definitively address the research question under study. PMID- 26839544 TI - Gastric Mucinous Cancer Histology: Clinicopathological Characteristics and Prognostic Value. AB - MC tended toward worse tumor biological behavior and long-term survival outcome compared to WMDC. Moreover, MC also showed worse clinicopathological features and survival outcome in some selected patients. For these reasons, MC should be deemed as a special histological type of gastric cancer with worse clinicopathological features and survival outcome. PMID- 26839545 TI - Quantitative Analysis of Intestinal Flora of Uygur and Han Ethnic Chinese Patients with Ulcerative Colitis. AB - Aim. To study the correlation between intestinal flora and ulcerative colitis by analyzing the abundance of Bacteroides, Fusobacterium, Clostridium, Bifidobacterium spp., and Faecalibacterium prausnitzii in the intestinal of ulcerative colitis (UC) patients and healthy controls with Uygur and Han ethnic. Methods. Bacterial genomic DNA was extracted from fecal samples and analyzed with real-time fluorescence quantitative polymerase chain reaction (PCR) to identify the abundance of Bacteroides, Fusobacterium, Clostridium, Bifidobacterium spp., and Faecalibacterium prausnitzii. Results. The samples from UC patients, Uygur and Han ethnic combined, had higher abundance of Bacteroides (P = 0.026) but lower Clostridium (P = 0.004), Bifidobacterium spp. (P = 0.009), and Faecalibacterium prausnitzii (P = 0.008) than those from healthy controls. Among UC patients, Bacteroides population was raised in acute UC patients (P <= 0.05), while the abundance of Clostridium, Bifidobacterium spp., Fusobacterium, and Faecalibacterium prausnitzii decreased (P <= 0.05) compared with the remission. In both UC patients group and control group, no difference was observed in the abundance of these 5 bacteria between the Han and the Uygur group. Conclusions. Variations in the abundance of these five bacterial strains in intestines may be associated with the occurrence of UC in Uygur and Han populations; however, these variations were not associated with ethnic difference. PMID- 26839546 TI - Cytotoxicity, Genotoxicity, and Phytotoxicity of Tannery Effluent Discharged into Palar River Basin, Tamil Nadu, India. AB - Ambur, a town located on the banks of Palar River, is considered one of the most polluted areas in India and occupied by hundreds of tanneries and leather product units. The present study was designed to evaluate the toxic effect of discharged tannery effluent (TE) on model agricultural crops, ecofriendly microorganisms, and human blood cells. The phytotoxic effects of TE tested on Allium cepa and Lemna minor revealed inhibition of root growth and significant reduction in number of fronds, protein, and chlorophyll content. Moreover, TE induced chlorosis and tissue necrosis in Nostoc muscorum at low concentration (10%). TE has also negative impact on ecofriendly microorganisms, Bacillus thuringiensis, Rhizobium etli, and Aspergillus terreus which play an important role in the nutrition of plant growth. The genotoxicity of TE was investigated in human leukocytes which showed interference with normal mitotic division with subsequent cell lysis. It also intervened with the normal replication process and induced micronucleus formation in the healthy leukocyte. 5% concentration of TE has been revealed to be toxic to erythrocytes. From this study TE found in the Palar River of Ambur has adverse effects on all the three levels of organisms in ecosystem even at lower concentrations. PMID- 26839548 TI - Knowledge of Future Dental Practitioners towards Oral Cancer: Exploratory Findings from a Public University in Malaysia. AB - Objective. To assess knowledge and awareness of oral cancer in the early identification of risk factors among undergraduate dental students. Methods. A total of 162 undergraduate (third, fourth, and fifth year) dental students at International Islamic University, Malaysia, were approached to participate in the study, and those who agreed were administered. A 9-item pretested questionnaire contains questions on oral examination, oral cancer risk factors, and requests for further information. Descriptive statistics were conducted using chi-square testing. Results. The response rate of the study was 70.3% (114/162), with 26 (22.8%) males and 88 (77.2%) females. All undergraduate dental students were familiar with examining the oral mucosa of their patients and most were likely to advise patients about the risk factors for developing oral cancer (98.2%). Nearly one-third (32.4%) of students reported examining patients with oral lesions as early signs for oral cancer (P < 0.001) and nearly 70% agreed that they did not have sufficient knowledge regarding the prevention and detection of oral cancer (P < 0.001). In addition, more than 95.6% agreed that there is a need for additional information/teaching regarding oral cancer. Further, 61.3% and 14.1% identified tobacco smoking and drinking alcohol as major risk factors for developing oral cancer. Conclusion. This study demonstrated lack of awareness about risk factors among undergraduate dental students regarding oral cancer. Reinforcing awareness and enhancing the benefits of early detection on prevention of oral cancer should be done through training and/or educational intervention. PMID- 26839549 TI - Near-Infrared Spectroscopy as an Analytical Process Technology for the On-Line Quantification of Water Precipitation Processes during Danhong Injection. AB - This paper used near-infrared (NIR) spectroscopy for the on-line quantitative monitoring of water precipitation during Danhong injection. For these NIR measurements, two fiber optic probes designed to transmit NIR radiation through a 2 mm flow cell were used to collect spectra in real-time. Partial least squares regression (PLSR) was developed as the preferred chemometrics quantitative analysis of the critical intermediate qualities: the danshensu (DSS, (R)-3, 4 dihydroxyphenyllactic acid), protocatechuic aldehyde (PA), rosmarinic acid (RA), and salvianolic acid B (SAB) concentrations. Optimized PLSR models were successfully built and used for on-line detecting of the concentrations of DSS, PA, RA, and SAB of water precipitation during Danhong injection. Besides, the information of DSS, PA, RA, and SAB concentrations would be instantly fed back to site technical personnel for control and adjustment timely. The verification experiments determined that the predicted values agreed with the actual homologic value. PMID- 26839547 TI - The Role of miR-378a in Metabolism, Angiogenesis, and Muscle Biology. AB - MicroRNA-378a (miR-378a, previously known as miR-378) is one of the small noncoding RNA molecules able to regulate gene expression at posttranscriptional level. Its two mature strands, miR-378a-3p and miR-378a-5p, originate from the first intron of the peroxisome proliferator-activated receptor gamma, coactivator 1 beta (ppargc1b) gene encoding PGC-1beta. Embedding in the sequence of this transcriptional regulator of oxidative energy metabolism implies involvement of miR-378a in metabolic pathways, mitochondrial energy homeostasis, and related biological processes such as muscle development, differentiation, and regeneration. On the other hand, modulating the expression of proangiogenic factors such as vascular endothelial growth factor, angiopoietin-1, or interleukin-8, influencing inflammatory reaction, and affecting tumor suppressors, such as SuFu and Fus-1, miR-378a is considered as a part of an angiogenic network in tumors. In the latter, miR-378a can evoke broader actions by enhancing cell survival, reducing apoptosis, and promoting cell migration and invasion. This review describes the current knowledge on miR-378a linking oxidative/lipid metabolism, muscle biology, and blood vessel formation. PMID- 26839550 TI - Effect of Bleaching and Thermocycling on Resin-Enamel Bond Strength. AB - The aim of this study was to evaluate the effect of bleaching and thermocycling on microshear bond strength of bonded resin composites to enamel. Enamel slices were prepared from ninety-six intact human premolars and resin composite cylinders were bonded by using Adper Single Bond 2 + Filtek Z350 or Filtek silorane adhesive and resin composite. Each essential group was randomly subdivided to two subgroups: control and bleaching. In bleaching group, 35% hydrogen peroxide was applied on samples. Thermocycling procedure was conducted between 5 degrees C and 55 degrees C, for 3.000 cycles on the half of each subgroup specimen. Then microshear bond strength was tested. Methacrylate-based resin composite had higher bond strength than silorane-based one. The meyhacrylate-based group without bleaching along with thermocycling showed the most bond strength, while bleaching with 35% carbamide peroxide on silorane-based group without thermocycling showed the least microshear bond strength. Bleaching caused a significant degradation on shear bond strength of silorane-based resin composites that bonded using self-etch adhesive resin systems. PMID- 26839551 TI - Management of Fetal Growth Arrest in One of Dichorionic Twins: Three Cases and a Literature Review. AB - Progressive fetal growth restriction (FGR) is often an indication for delivery. In dichorionic diamniotic (DD) twin pregnancy with growth restriction only affecting one fetus (selective fetal growth restriction: sFGR), the normal twin is also delivered prematurely. There is still not enough evidence about the optimal timing of delivery for DD twins with sFGR in relation to discordance and gestational age. We report three sets of DD twins with sFGR (almost complete growth arrest affecting one fetus for >=2 weeks) before 30 weeks of gestation. The interval from growth arrest to delivery was 21-24 days and the discordance was 33.7-49.8%. A large-scale study showed no difference of overall mortality or the long-term outcome between immediate and delayed delivery for FGR, while many studies have identified a risk of developmental delay following delivery of the normal growth fetus before 32 weeks. Therefore, delivery of DD twins with sFGR should be delayed if the condition of the sFGR fetus permits in order to increase the gestational age of the normal growth fetus. PMID- 26839553 TI - TGF-beta1 Induces the Dual Regulation of Hepatic Progenitor Cells with Both Anti- and Proliver Fibrosis. AB - Transforming growth factor-beta 1 (TGF-beta1) plays a central role in hepatic progenitor cells- (HPCs-) mediated liver repair and fibrosis. However, different effects of TGF-beta1 on progenitor cells have not been described. In this study, both in vitro (HPCs cocultured with hepatic stellate cells (HSCs) in transwells) and in vivo (CCl4-injured liver fibrosis rat) systems were used to evaluate the impacts. We found that HPCs pretreated with TGF-beta1 for 12 hours inhibited the activation of HSCs, while sensitization for 48 hours increased the activation of HSCs. Consistent with these in vitro results, the in vivo fibrosis rat model showed the same time-dependent dual effect of TGF-beta1. Regression of liver fibrosis as well as normalization of serum aminotransferase and albumin levels was detected in the rats transplanted with HPCs pretreated with TGF-beta1 for 12 hours. In contrast, severe liver fibrosis and elevated collagen-1 levels were detected in the rats transplanted with HPCs pretreated with TGF-beta1 for 48 hours. Furthermore, the TGF-beta1-pretreated HPCs were shown to deactivate HSCs via enhancing SERPINE1 expression. Inhibition of SERPINE1 reversed the deactivation response in a dose-dependent manner. PMID- 26839552 TI - Nanoparticles-Assisted Stem Cell Therapy for Ischemic Heart Disease. AB - Stem cell therapy has attracted increasing attention as a promising treatment strategy for cardiac repair in ischemic heart disease. Nanoparticles (NPs), with their superior physical and chemical properties, have been widely utilized to assist stem cell therapy. With the help of NPs, stem cells can be genetically engineered for enhanced paracrine profile. To further understand the fate and behaviors of stem cells in ischemic myocardium, imaging NPs can label stem cells and be tracked in vivo under multiple modalities. Besides that, NPs can also be used to enhance stem cell retention in myocardium. These facts have raised efforts on the development of more intelligent and multifunctional NPs for cellular application. Herein, an overview of the applications of NPs-assisted stem cell therapy is given. Key issues and future prospects are also critically addressed. PMID- 26839554 TI - Emerging Implications for Extracellular Matrix-Based Technologies in Vascularized Composite Allotransplantation. AB - Despite recent progress in vascularized composite allotransplantation (VCA), limitations including complex, high dose immunosuppression regimens, lifelong risk of toxicity from immunosuppressants, acute and most critically chronic graft rejection, and suboptimal nerve regeneration remain particularly challenging obstacles restricting clinical progress. When properly configured, customized, and implemented, biomaterials derived from the extracellular matrix (ECM) retain bioactive molecules and immunomodulatory properties that can promote stem cell migration, proliferation and differentiation, and constructive functional tissue remodeling. The present paper reviews the emerging implications of ECM-based technologies in VCA, including local immunomodulation, tissue repair, nerve regeneration, minimally invasive graft targeted drug delivery, stem cell transplantation, and other donor graft manipulation. PMID- 26839555 TI - Multiple Functions of MSCA-1/TNAP in Adult Mesenchymal Progenitor/Stromal Cells. AB - Our knowledge about mesenchymal stem cells has considerably grown in the last years. Since the proof of concept of the existence of such cells in the 70s by Friedenstein et al., a growing mass of reports were conducted for a better definition of these cells and for the reevaluation from the term "mesenchymal stem cells" to the term "mesenchymal stromal cells (MSCs)." Being more than a semantic shift, concepts behind this new terminology reveal the complexity and the heterogeneity of the cells grouped in MSC family especially as these cells are present in nearly all adult tissues. Recently, mesenchymal stromal cell antigen-1 (MSCA-1)/tissue nonspecific alkaline phosphatase (TNAP) was described as a new cell surface marker of MSCs from different tissues. The alkaline phosphatase activity of this protein could be involved in wide range of MSC features described below from cell differentiation to immunomodulatory properties, as well as occurrence of pathologies. The present review aims to decipher and summarize the role of TNAP in progenitor cells from different tissues focusing preferentially on brain, bone marrow, and adipose tissue. PMID- 26839557 TI - Immunotolerant Properties of Mesenchymal Stem Cells: Updated Review. AB - Stem cell transplantation is a potential therapeutic option to regenerate damaged myocardium and restore function after infarct. Current research is focused on the use of allogeneic mesenchymal stem cells (MSCs) due to their unique immunomodulatory characteristics and ability to be harvested from young and healthy donors. Both animal and human studies support the immunoprivileged state of MSCs and even demonstrate improvements in cardiac function after transplantation. This research continues to be a topic of interest, as advances will ultimately enable the clinical use of these universal cells for therapy after a myocardial infarction. Updated in vitro, in vivo, and clinical trial studies are discussed in detail in the following review. PMID- 26839558 TI - Endothelium-Independent Hypoxic Contraction Is Prevented Specifically by Nitroglycerin via Inhibition of Akt Kinase in Porcine Coronary Artery. AB - Objective. Hypoxia-induced sustained contraction of porcine coronary artery is endothelium-independent and mediated by PI3K/Akt/Rho kinase. Nitroglycerin (NTG) is a vasodilator used to treat angina pectoris and acute heart failure. The present study was to determine the role of NTG in hypoxia-induced endothelium independent contraction and the underlying mechanism. Methods and Results. Organ chamber technique was used to measure the isometric vessel tension of isolated porcine coronary arteries. Protein levels of phosphorylated and total Akt were determined by western blot. A sustained contraction of porcine coronary arteries induced by hypoxia was significantly reduced by NTG but not by isoproterenol. This contraction was also inhibited by DETA NONOate, 8-Br-cGMP, which can be reversed by ODQ, and Rp-8-Br-PET-cGMPS. The restored contraction was blocked by LY294002. The reduction of Akt-p at Ser-473 by NTG, DETA NONOate, and 8-Br-cGMP was significantly inhibited by ODQ, PKG-I. The decrease in Akt-p level by NTG and 8-Br-cGMP was prevented by calyculin A but not by okadaic acid. Conclusions. These results demonstrated that the endothelium-independent sustained hypoxic vasoconstriction can be prevented by NTG and that the inhibition of PI3K/Akt signaling pathway may be involved. PMID- 26839556 TI - Metaboloepigenetic Regulation of Pluripotent Stem Cells. AB - The differentiation of pluripotent stem cells is associated with extensive changes in metabolism, as well as widespread remodeling of the epigenetic landscape. Epigenetic regulation is essential for the modulation of differentiation, being responsible for cell type specific gene expression patterns through the modification of DNA and histones, thereby establishing cell identity. Each cell type has its own idiosyncratic pattern regarding the use of specific metabolic pathways. Rather than simply being perceived as a means of generating ATP and building blocks for cell growth and division, cellular metabolism can directly influence cellular regulation and the epigenome. Consequently, the significance of nutrients and metabolites as regulators of differentiation is central to understanding how cells interact with their immediate environment. This review serves to integrate studies on pluripotent stem cell metabolism, and the regulation of DNA methylation and acetylation and identifies areas in which current knowledge is limited. PMID- 26839560 TI - Hematopoietic Stem and Progenitor Cell Expansion in Contact with Mesenchymal Stromal Cells in a Hanging Drop Model Uncovers Disadvantages of 3D Culture. AB - Efficient ex vivo expansion of hematopoietic stem cells with a concomitant preservation of stemness and self-renewal potential is still an unresolved ambition. Increased numbers of methods approaching this issue using three dimensional (3D) cultures were reported. Here, we describe a simplified 3D hanging drop model for the coculture of cord blood-derived CD34(+) hematopoietic stem and progenitor cells (HSPCs) with bone marrow-derived mesenchymal stromal cells (MSCs). When seeded as a mixed cell suspension, MSCs segregated into tight spheroids. Despite the high expression of niche-specific extracellular matrix components by spheroid-forming MSCs, HSPCs did not migrate into the spheroids in the initial phase of coculture, indicating strong homotypic interactions of MSCs. After one week, however, HSPC attachment increased considerably, leading to spheroid collapse as demonstrated by electron microscopy and immunofluorescence staining. In terms of HSPC proliferation, the conventional 2D coculture system was superior to the hanging drop model. Furthermore, expansion of primitive hematopoietic progenitors was more favored in 2D than in 3D, as analyzed in colony-forming assays. Conclusively, our data demonstrate that MSCs, when arranged with a spread (monolayer) shape, exhibit better HSPC supportive qualities than spheroid-forming MSCs. Therefore, 3D systems are not necessarily superior to traditional 2D culture in this regard. PMID- 26839561 TI - Human Umbilical Cord Blood-Derived Serum for Culturing the Supportive Feeder Cells of Human Pluripotent Stem Cell Lines. AB - Although human pluripotent stem cells (hPSCs) can proliferate robustly on the feeder-free culture system, genetic instability of hPSCs has been reported in such environment. Alternatively, feeder cells enable hPSCs to maintain their pluripotency. The feeder cells are usually grown in a culture medium containing fetal bovine serum (FBS) prior to coculture with hPSCs. The use of FBS might limit the clinical application of hPSCs. Recently, human cord blood-derived serum (hUCS) showed a positive effect on culture of mesenchymal stem cells. It is interesting to test whether hUCS can be used for culture of feeder cells of hPSCs. This study was aimed to replace FBS with hUCS for culturing the human foreskin fibroblasts (HFFs) prior to feeder cell preparation. The results showed that HFFs cultured in hUCS-containing medium (HFF-hUCS) displayed fibroblastic features, high proliferation rates, short population doubling times, and normal karyotypes after prolonged culture. Inactivated HFF-hUCS expressed important genes, including Activin A, FGF2, and TGFbeta1, which have been implicated in the maintenance of hPSC pluripotency. Moreover, hPSC lines maintained pluripotency, differentiation capacities, and karyotypic stability after being cocultured for extended period with inactivated HFF-hUCS. Therefore, the results demonstrated the benefit of hUCS for hPSCs culture system. PMID- 26839559 TI - Engineering Tendon: Scaffolds, Bioreactors, and Models of Regeneration. AB - Tendons bridge muscle and bone, translating forces to the skeleton and increasing the safety and efficiency of locomotion. When tendons fail or degenerate, there are no effective pharmacological interventions. The lack of available options to treat damaged tendons has created a need to better understand and improve the repair process, particularly when suitable autologous donor tissue is unavailable for transplantation. Cells within tendon dynamically react to loading conditions and undergo phenotypic changes in response to mechanobiological stimuli. Tenocytes respond to ultrastructural topography and mechanical deformation via a complex set of behaviors involving force-sensitive membrane receptor activity, changes in cytoskeletal contractility, and transcriptional regulation. Effective ex vivo model systems are needed to emulate the native environment of a tissue and to translate cell-matrix forces with high fidelity. While early bioreactor designs have greatly expanded our knowledge of mechanotransduction, traditional scaffolds do not fully model the topography, composition, and mechanical properties of native tendon. Decellularized tendon is an ideal scaffold for cultivating replacement tissue and modeling tendon regeneration. Decellularized tendon scaffolds (DTS) possess high clinical relevance, faithfully translate forces to the cellular scale, and have bulk material properties that match natural tissue. This review summarizes progress in tendon tissue engineering, with a focus on DTS and bioreactor systems. PMID- 26839562 TI - Biocompatibility Assessment of PLCL-Sericin Copolymer Membranes Using Wharton's Jelly Mesenchymal Stem Cells. AB - Stem cells based tissue engineering requires biocompatible materials, which allow the cells to adhere, expand, and differentiate in a large scale. An ideal biomaterial for clinical application should be free from mammalian products which cause immune reactivities and pathogen infections. We invented a novel biodegradable poly(L-lactic-co-epsilon-caprolactone)-sericin (PLCL-SC) copolymer membrane which was fabricated by electrospinning. Membranes with concentrations of 2.5 or 5% (w/v) SC exhibited qualified texture characteristics with a noncytotoxic release profile. The hydrophilic properties of the membranes were 35 40% higher than those of a standard PLCL and commercial polystyrene (PS). The improved characteristics of the membranes were due to an addition of new functional amide groups, C=O, N-H, and C-N, onto their surfaces. Degradation of the membranes was controllable, depending on the content proportion of SC. Results of thermogram indicated the superior stability and crystallinity of the membranes. These membranes enhanced human Wharton's jelly mesenchymal stem cells (hWJMSC) proliferation by increasing cyclin A and also promoted cell adhesion by upregulating focal adhesion kinase (FAK). On the membranes, hWJMSC differentiated into a neuronal lineage with the occurrence of nestin. These data suggest that PLCL-SC electrospun membrane represents some properties which will be useful for tissue engineering and medical applications. PMID- 26839563 TI - Comparison of Signaling Pathways Gene Expression in CD34(-) Umbilical Cord Blood and Bone Marrow Stem Cells. AB - The aim of the study was to compare the biological activity of the total pool of genes in CD34(-) umbilical cord blood and bone marrow stem cells and to search for the differences in signaling pathway gene expression responsible for the biological processes. The introductory analysis revealed a big similarity of gene expression among stem cells. When analyzing GO terms for biological processes, we observed an increased activity of JAK-STAT signaling pathway, calcium-mediated, cytokine-mediated, integrin-mediated signaling pathway, and MAPK in a cluster of upregulating genes in CD34(-) umbilical cord blood stem cells. At the same time, we observed a decreased activity of BMP signaling pathways, TGF-beta pathway, and VEGF receptor signaling pathway in a cluster of downregulating genes in CD34(-) umbilical cord blood stem cells. In accordance with KEGG classification, the cytokine-cytokine receptor interaction, toll-like receptor signaling pathway, and JAK-STAT signaling pathway are overrepresented in CD34(-) umbilical cord blood stem cells. A similar gene expression in both CD34(-) UCB and BM stem cells was characteristic for such biological processes as cell division, cell cycle gene expression, mitosis, telomere maintenance with telomerase, RNA and DNA treatment processes during cell division, and similar genes activity of Notch and Wnt signaling pathways. PMID- 26839564 TI - Comparison of the Treatment Efficiency of Bone Marrow-Derived Mesenchymal Stem Cell Transplantation via Tail and Portal Veins in CCl4-Induced Mouse Liver Fibrosis. AB - Because of self-renewal, strong proliferation in vitro, abundant sources for isolation, and a high differentiation capacity, mesenchymal stem cells are suggested to be potentially therapeutic for liver fibrosis/cirrhosis. In this study, we evaluated the treatment effects of mouse bone marrow-derived mesenchymal stem cells (BM-MSCs) on mouse liver cirrhosis induced by carbon tetrachloride. Portal and tail vein transplantations were examined to evaluate the effects of different injection routes on the liver cirrhosis model at 21 days after transplantation. BM-MSCs transplantation reduced aspartate aminotransferase/alanine aminotransferase levels at 21 days after injection. Furthermore, BM-MSCs induced positive changes in serum bilirubin and albumin and downregulated expression of integrins (600- to 7000-fold), transforming growth factor, and procollagen-alpha1 compared with the control group. Interestingly, both injection routes ameliorated inflammation and liver cirrhosis scores. All mice in treatment groups had reduced inflammation scores and no cirrhosis. In conclusion, transplantation of BM-MSCs via tail or portal veins ameliorates liver cirrhosis in mice. Notably, there were no differences in treatment effects between tail and portal vein administrations. In consideration of safety, we suggest transfusion of bone marrow-derived mesenchymal stem cells via a peripheral vein as a potential method for liver fibrosis treatment. PMID- 26839565 TI - Epigenetic Reprogramming of Muscle Progenitors: Inspiration for Clinical Therapies. AB - In the context of regenerative medicine, based on the potential of stem cells to restore diseased tissues, epigenetics is becoming a pivotal area of interest. Therapeutic interventions that promote tissue and organ regeneration have as primary objective the selective control of gene expression in adult stem cells. This requires a deep understanding of the epigenetic mechanisms controlling transcriptional programs in tissue progenitors. This review attempts to elucidate the principle epigenetic regulations responsible of stem cells differentiation. In particular we focus on the current understanding of the epigenetic networks that regulate differentiation of muscle progenitors by the concerted action of chromatin-modifying enzymes and noncoding RNAs. The novel exciting role of exosome-bound microRNA in mediating epigenetic information transfer is also discussed. Finally we show an overview of the epigenetic strategies and therapies that aim to potentiate muscle regeneration and counteract the progression of Duchenne Muscular Dystrophy (DMD). PMID- 26839566 TI - The Immunomodulatory Effects of Mesenchymal Stem Cells in Prevention or Treatment of Excessive Scars. AB - Excessive scars, including keloids and hypertrophic scars, result from aberrations in the process of physiologic wound healing. An exaggerated inflammatory process is one of the main pathophysiological contributors. Scars may cause pain, and pruritis, limit joint mobility, and cause a range of cosmetic deformities that affect the patient's quality of life. Extensive research has been done on hypertrophic scar and keloid formation that has resulted in the plethora of treatment and prevention methods practiced today. Mesenchymal stem cells, among their multifunctional roles, are known regulators of inflammation and have been receiving attention as a major candidate for cell therapy to treat or prevent excessive scars. This paper extensively reviews the body of research examining the mechanism and potential of stem cell therapy in the treatment of excessive scars. PMID- 26839567 TI - A Dishful of a Troubled Mind: Induced Pluripotent Stem Cells in Psychiatric Research. AB - Neuronal differentiation of induced pluripotent stem cells and direct reprogramming represent powerful methods for modeling the development of neurons in vitro. Moreover, this approach is also a means for comparing various cellular phenotypes between cell lines originating from healthy and diseased individuals or isogenic cell lines engineered to differ at only one or a few genomic loci. Despite methodological constraints and initial skepticism regarding this approach, the field is expanding at a fast pace. The improvements include the development of new differentiation protocols resulting in selected neuronal populations (e.g., dopaminergic, GABAergic, hippocampal, and cortical), the widespread use of genome editing methods, and single-cell techniques. A major challenge awaiting in vitro disease modeling is the integration of clinical data in the models, by selection of well characterized clinical populations. Ideally, these models will also demonstrate how different diagnostic categories share overlapping molecular disease mechanisms, but also have unique characteristics. In this review we evaluate studies with regard to the described developments, to demonstrate how differentiation of induced pluripotent stem cells and direct reprogramming can contribute to psychiatry. PMID- 26839570 TI - Cartilage Defect Treatments: With or without Cells? Mesenchymal Stem Cells or Chondrocytes? Traditional or Matrix-Assisted? A Systematic Review and Meta Analyses. AB - Articular cartilage defects have been addressed by using multiple strategies. In the last two decades, promising new strategies by using assorted scaffolds and cell sources to induce tissue regeneration have emerged, such as autologous chondrocyte implantation (ACI) and mesenchymal stem cell implantation (MSCI). However, it is still controversial in the clinical strategies when to choose these treatments. Thus, we conducted a systematic review and meta-analyses to compare the efficacy and safety of different cartilage treatments. In our study, 17 studies were selected to compare different treatments for cartilage defects. The results of meta-analyses indicated that cell-based cartilage treatments showed significant better efficacy than cell-free treatments did (OR: 4.27, 95% CI: 2.19-8.34; WMD: 10.11, 95% CI: 2.69-16.53). Another result indicated that MACT had significant better efficacy than traditional ACI did (OR: 0.49, 95% CI: 0.30-0.82). Besides, the incidence of graft hypertrophy of MACT was slightly lower than that of traditional ACI (OR: 2.43, 95% CI: 1.00-5.94). Current data showed that the cell-based treatments and MACT are better options for cartilage treatments, but more well-designed comparative studies are still needed to enhance our understanding of different treatments for cartilage defects. PMID- 26839569 TI - Endothelial Progenitor Cells for Diagnosis and Prognosis in Cardiovascular Disease. AB - Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs) in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to "endothelial progenitor cells" and "endothelium" and, for the different categories, respectively, "smoking"; "blood pressure"; "diabetes mellitus" or "insulin resistance"; "dyslipidemia"; "aging" or "elderly"; "angina pectoris" or "myocardial infarction"; "stroke" or "cerebrovascular disease"; "homocysteine"; "C-reactive protein"; "vitamin D". Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717. PMID- 26839571 TI - Effect of Fibroblast Growth Factor 2 on Equine Synovial Fluid Chondroprogenitor Expansion and Chondrogenesis. AB - Mesenchymal stem cells have been identified in the synovial fluid of several species. This study was conducted to characterize chondroprogenitor (CP) cells in equine synovial fluid (SF) and to determine the effect of fibroblast growth factor 2 (FGF-2) on SF-CP monolayer proliferation and subsequent chondrogenesis. We hypothesized that FGF-2 would stimulate SF-CP proliferation and postexpansion chondrogenesis. SF aspirates were collected from adult equine joints. Colony forming unit (CFU) assays were performed during primary cultures. At first passage, SF-cells were seeded at low density, with or without FGF-2. Following monolayer expansion and serial immunophenotyping, cells were transferred to chondrogenic pellet cultures. Pellets were analyzed for chondrogenic mRNA expression and cartilage matrix secretion. There was a mean of 59.2 CFU/mL of SF. FGF-2 increased the number of population doublings during two monolayer passages and halved the population doubling times. FGF-2 did not alter the immunophenotype of SF-CPs during monolayer expansion, nor did FGF-2 compromise chondrogenesis. Hypertrophic phenotypic markers were not expressed in control or FGF-2 groups. FGF-2 did prevent the development of a "fibroblastic" cell layer around pellet periphery. FGF-2 significantly accelerates in vitro SF-CP expansion, the major hurdle to clinical application of this cell population, without detrimentally affecting subsequent chondrogenic capacity. PMID- 26839568 TI - Stem Cell Tracking with Nanoparticles for Regenerative Medicine Purposes: An Overview. AB - Accurate and noninvasive stem cell tracking is one of the most important needs in regenerative medicine to determine both stem cell destinations and final differentiation fates, thus allowing a more detailed picture of the mechanisms involved in these therapies. Given the great importance and advances in the field of nanotechnology for stem cell imaging, currently, several nanoparticles have become standardized products and have been undergoing fast commercialization. This review has been intended to summarize the current use of different engineered nanoparticles in stem cell tracking for regenerative medicine purposes, in particular by detailing their main features and exploring their biosafety aspects, the first step for clinical application. Moreover, this review has summarized the advantages and applications of stem cell tracking with nanoparticles in experimental and preclinical studies and investigated present limitations for their employment in the clinical setting. PMID- 26839572 TI - Regional Variation in Human Exposure to Persistent Organic Pollutants in the United States, NHANES. AB - We examined serum levels of persistent organic pollutants (POPs) among geographical regions of the United States as defined by the US Census Bureau. National Health and Nutrition Examination Survey (NHANES) data for adults aged 20 years and older are presented for selected survey periods between 1999 and 2010. From NHANES 1999 through 2004, dichlorodiphenyldichloroethylene (DDE) concentration levels were consistently higher among people living in the West than in the Midwest, Northeast, or South. In 2003-2010, perfluorinated compound concentrations tended to be highest in the South. The sum of 35 polychlorinated biphenyls (PCBs) congeners was significantly higher in the Northeast [GM: 189; 95% CI: 173-204 ng/g lipid] than the remaining regions. The regional differences in higher body burdens of exposure to particular POPs could be attributed to a variety of activities, including region-specific patterns of land use and industrial and agricultural chemical applications, as well as different levels of regulatory activity. PMID- 26839573 TI - Compliance with Iron-Folate Supplement and Associated Factors among Antenatal Care Attendant Mothers in Misha District, South Ethiopia: Community Based Cross Sectional Study. AB - Background. In Ethiopia, higher proportions of pregnant women are anemic. Despite the efforts to reduce iron deficiency anemia during pregnancy, only few women took an iron supplement as recommended. Thus, this study aimed to assess compliance with iron-folate supplement and associated factors among antenatal care attendant mothers in Misha district, South Ethiopia. Method. Community based cross-sectional study supported with in-depth interview was conducted from March 1 to March 30, 2015. The sample size was determined using single population proportion to 303. Simple random sampling technique was used to select the study participants. Bivariate and multivariable logistic regression analyses were employed to identify factors associated with compliance to iron-folate supplement. Results. The compliance rate was found to be 39.2%. Mothers knowledge of anemia (AOR = 4.451, 95% CI = (2.027,9.777)), knowledge of iron-folate supplement (AOR = 3.509, 95% CI = (1.442,8.537)), and counseling on iron-folate supplement (AOR = 4.093, 95% CI = (2.002,8.368)) were significantly associated with compliance to iron-folate supplement. Conclusions. Compliance rate of iron folate supplementation during pregnancy remains very low. This study showed that providing women with clear instructions about iron-folate tablet intake and educating them on the health benefits of the iron-folate tablets can increase compliance with iron-folate supplementation. PMID- 26839575 TI - Hypertension and diabetes in Africa: design and implementation of a large population-based study of burden and risk factors in rural and urban Malawi. AB - BACKGROUND: The emerging burden of cardiovascular disease and diabetes in sub Saharan Africa threatens the gains made in health by the major international effort to combat infectious diseases. There are few data on distribution of risk factors and outcomes in the region to inform an effective public health response. A comprehensive research programme is being developed aimed at accurately documenting the burden and drivers of NCDs in urban and rural Malawi; to design and test intervention strategies. The programme includes population surveys of all people aged 18 years and above, linking individuals with newly diagnosed hypertension and diabetes to healthcare and supporting clinical services. The successes, challenges and lessons learnt from the programme to date are discussed. RESULTS: Over 20,000 adults have been recruited in rural Karonga and urban Lilongwe. The urban population is significantly younger and wealthier than the rural population. Employed urban individuals, particularly males, give particular recruitment challenges; male participation rates were 80.3 % in the rural population and 43.6 % in urban, whilst female rates were 93.6 and 75.6 %, respectively. The study is generating high quality data on hypertension, diabetes, lipid abnormalities and risk factors. CONCLUSIONS: It is feasible to develop large scale studies that can reliably inform the public health approach to diabetes, cardiovascular disease and other NCDs in Sub-Saharan Africa. It is essential for studies to capture both rural and urban populations to address disparities in risk factors, including age structure. Innovative approaches are needed to address the specific challenge of recruiting employed urban males. PMID- 26839574 TI - Efforts of the human immune system to maintain the peripheral CD8+ T cell compartment after childhood thymectomy. AB - BACKGROUND: Homeostatic mechanisms to maintain the T cell compartment diversity indicate an ongoing process of thymic activity and peripheral T cell renewal during human life. These processes are expected to be accelerated after childhood thymectomy and by the influence of cytomegalovirus (CMV) inducing a prematurely aged immune system. The study aimed to investigate proportional changes and replicative history of CD8+ T cells, of recent thymic emigrants (RTEs) and CD103+ T cells (mostly gut-experienced) and the role of Interleukin-(IL)-7 and IL-7 receptor (CD127)-expressing T cells in thymectomized patients compared to young and old healthy controls. RESULTS: Decreased proportions of naive and CD31 + CD8+ T cells were demonstrated after thymectomy, with higher proliferative activity of CD127-expressing T cells and significantly shorter relative telomere lengths (RTLs) and lower T cell receptor excision circles (TRECs). Increased circulating CD103+ T cells and a skewed T cell receptor (TCR) repertoire were found after thymectomy similar to elderly persons. Naive T cells were influenced by age at thymectomy and further decreased by CMV. CONCLUSIONS: After childhood thymectomy, the immune system demonstrated constant efforts of the peripheral CD8+ T cell compartment to maintain homeostasis. Supposedly it tries to fill the void of RTEs by peripheral T cell proliferation, by at least partly IL-7-mediated mechanisms and by proportional increase of circulating CD103+ T cells, reminiscent of immune aging in elderly. Although other findings were less significant compared to healthy elderly, early thymectomy demonstrated immunological alterations of CD8+ T cells which mimic features of premature immunosenescence in humans. PMID- 26839576 TI - Erratum to: Baseline insulin sensitivity affects response to high-amylose maize resistant starch in women: a randomized, controlled trial. AB - [This corrects the article DOI: 10.1186/s12986-016-0062-5.]. PMID- 26839577 TI - Leptin receptor signaling is required for high-fat diet-induced atrophic gastritis in mice. AB - BACKGROUND: Obesity increases the risk for malignancies in various tissues including the stomach. Atrophic gastritis with precancerous lesions is an obesity associated disease; however, the mechanisms that underlie the development of obesity-associated atrophic gastritis are unknown. Leptin is a hormone derived from stomach as well as adipose tissue and gastric leptin is involved in the development of gastric cancer. The aim of the current study is to investigate the involvement of leptin receptor signaling in the development of atrophic gastritis during diet-induced obesity. METHODS: Male C57BL/6, ob/ob and db/db mice were fed a high-fat diet (HFD) or a control diet (CD) from 1 week to 5 months. Pathological changes of the gastric mucosa and the expression of molecules associated with atrophic gastritis were evaluated in these mice. RESULTS: HFD feeding induced gastric mucosal hyperplasia with increased gastric leptin expression. Mucosal hyperplasia was accompanied by a higher frequency of Ki67 positive proliferating cells and atrophy of the gastric glands in the presence of inflammation, which increased following HFD feeding. Activation of ObR signaling associated molecules such as ObR, STAT3, Akt, and ERK was detected in the gastric mucosa of mice fed the HFD for 1 week. The morphological alterations associated with gastric mucosal atrophy and the expression of Muc2 and Cdx2 resemble those associated with human intestinal metaplasia. In contrast to wild-type mice, leptin-deficient ob/ob mice and leptin receptor-mutated db/db mice did not show increased Cdx2 expression in response to HFD feeding. CONCLUSION: Together, these results suggest that activation of the leptin signaling pathway in the stomach is required to develop obesity-associated atrophic gastritis. PMID- 26839578 TI - Dietary intake of cod and scallop reduces atherosclerotic burden in female apolipoprotein E-deficient mice fed a Western-type high fat diet for 13 weeks. AB - BACKGROUND: It is now increasingly recognized that the beneficial effects of seafood consumption is not limited to lipids and fatty acid, but that the protein part, i.e., peptides and amino acids, together with vitamins and even unknown bioactive constituents also are important for disease prevention. This study was designed to evaluate the putative anti-atherogenic effects of different protein sources (a lean seafood and a nonseafood) in apolipoprotein E-deficient (apoE(-/ )) mice. METHODS: Twenty-four 5-week-old female apoE(-/-) mice were fed Western type diets containing chicken or a combination of cod and scallops as dietary protein sources for 13 weeks. Atherosclerotic plaque burden, weight, serum levels of leptin, glucose and LDL cholesterol as well as gene expressions from liver and heart were evaluated. Statistical analyses were performed using SPSS. Differences between the variables were evaluated using independent t-test or Mann-Whitney U test for normally and non-normally distributed variables, respectively. Normality was defined by the Shapiro-Wilk test. RESULTS: The mice fed cod-scallop had a 24 % (p < 0.05) reduced total aorta atherosclerotic plaque burden compared to the chicken fed group, whereas the reduction in plaque in the less lesion prone thoracic and abdominal parts of the descending aorta were 46 % (p < 0.05) and 56 % (p < 0.05), respectively. In addition, mice fed cod-scallop gained less weight, and had lower serum levels of leptin, glucose and LDL cholesterol, compared to those fed chicken. Analysis of expression of the genes from liver and heart showed that hepatic endogenous antioxidant paraoxonase 2 (Pon2 gene) and the vascular cell adhesion molecule VCAM-1 (Vcam1 gene) were down regulated in mice fed cod-scallop compared to mice fed chicken. CONCLUSION: The present study revealed a metabolic beneficial effect of lean seafood compared to chicken, as atherosclerotic plaque burden, serum glucose, leptin and LDL cholesterol levels were reduced in mice fed cod-scallop. PMID- 26839579 TI - A modular toolbox for gRNA-Cas9 genome engineering in plants based on the GoldenBraid standard. AB - BACKGROUND: The efficiency, versatility and multiplexing capacity of RNA-guided genome engineering using the CRISPR/Cas9 technology enables a variety of applications in plants, ranging from gene editing to the construction of transcriptional gene circuits, many of which depend on the technical ability to compose and transfer complex synthetic instructions into the plant cell. The engineering principles of standardization and modularity applied to DNA cloning are impacting plant genetic engineering, by increasing multigene assembly efficiency and by fostering the exchange of well-defined physical DNA parts with precise functional information. RESULTS: Here we describe the adaptation of the RNA-guided Cas9 system to GoldenBraid (GB), a modular DNA construction framework being increasingly used in Plant Synthetic Biology. In this work, the genetic elements required for CRISPRs-based editing and transcriptional regulation were adapted to GB, and a workflow for gRNAs construction was designed and optimized. New software tools specific for CRISPRs assembly were created and incorporated to the public GB resources site. CONCLUSIONS: The functionality and the efficiency of gRNA-Cas9 GB tools were demonstrated in Nicotiana benthamiana using transient expression assays both for gene targeted mutations and for transcriptional regulation. The availability of gRNA-Cas9 GB toolbox will facilitate the application of CRISPR/Cas9 technology to plant genome engineering. PMID- 26839580 TI - Gene targeting and transgene stacking using intra genomic homologous recombination in plants. AB - Modern agriculture has created a demand for plant biotechnology products that provide durable resistance to insect pests, tolerance of herbicide applications for weed control, and agronomic traits tailored for specific geographies. These transgenic trait products require a modular and sequential multigene stacking platform that is supported by precise genome engineering technology. Designed nucleases have emerged as potent tools for creating targeted DNA double strand breaks (DSBs). Exogenously supplied donor DNA can repair the targeted DSB by a process known as gene targeting (GT), resulting in a desired modification of the target genome. The potential of GT technology has not been fully realized for trait deployment in agriculture, mainly because of inefficient transformation and plant regeneration systems in a majority of crop plants and genotypes. This challenge of transgene stacking in plants could be overcome by Intra-Genomic Homologous Recombination (IGHR) that converts independently segregating unlinked donor and target transgenic loci into a genetically linked molecular stack. The method requires stable integration of the donor DNA into the plant genome followed by intra-genomic mobilization. IGHR complements conventional breeding with genetic transformation and designed nucleases to provide a flexible transgene stacking and trait deployment platform. PMID- 26839581 TI - Identification of an attenuated barley stripe mosaic virus for the virus-induced gene silencing of pathogenesis-related wheat genes. AB - BACKGROUND: Virus-induced gene silencing (VIGS) has become an emerging technology for the rapid, efficient functional genomic screening of monocot and dicot species. The barley stripe mosaic virus (BSMV) has been described as an effective VIGS vehicle for the evaluation of genes involved in wheat and barley phytopathogenesis; however, these studies have been obscured by BSMV-induced phenotypes and defense responses. The utility of BSMV VIGS may be improved using a BSMV genetic background which is more tolerable to the host plant especially upon secondary infection of highly aggressive, necrotrophic pathogens such as Fusarium graminearum. RESULTS: BSMV-induced VIGS in Triticum aestivum (bread wheat) cv. 'Fielder' was assessed for the study of wheat genes putatively related to Fusarium Head Blight (FHB), the necrotrophism of wheat and other cereals by F. graminearum. Due to the lack of 'Fielder' spike viability and increased accumulation of Fusarium-derived deoxynivalenol contamination upon co-infection of BSMV and FHB, an attenuated BSMV construct was generated by the addition of a glycine-rich, C-terminal peptide to the BSMV gamma b protein. This attenuated BSMV effectively silenced target wheat genes while limiting disease severity, deoxynivalenol contamination, and yield loss upon Fusarium co-infection compared to the original BSMV construct. The attenuated BSMV-infected tissue exhibited reduced abscisic, jasmonic, and salicylic acid defense phytohormone accumulation upon secondary Fusarium infection. Finally, the attenuated BSMV was used to investigate the role of the salicylic acid-responsive pathogenesis-related 1 in response to FHB. CONCLUSIONS: The use of an attenuated BSMV may be advantageous in characterizing wheat genes involved in phytopathogenesis, including Fusarium necrotrophism, where minimal viral background effects on defense are required. Additionally, the attenuated BSMV elicits reduced defense hormone accumulation, suggesting that this genotype may have applications for the investigation of phytohormone-related signaling, developmental responses, and pathogen defense. PMID- 26839582 TI - Modeling Gene Networks in Saccharomyces cerevisiae Based on Gene Expression Profiles. AB - Detailed and innovative analysis of gene regulatory network structures may reveal novel insights to biological mechanisms. Here we study how gene regulatory network in Saccharomyces cerevisiae can differ under aerobic and anaerobic conditions. To achieve this, we discretized the gene expression profiles and calculated the self-entropy of down- and upregulation of gene expression as well as joint entropy. Based on these quantities the uncertainty coefficient was calculated for each gene triplet, following which, separate gene logic networks were constructed for the aerobic and anaerobic conditions. Four structural parameters such as average degree, average clustering coefficient, average shortest path, and average betweenness were used to compare the structure of the corresponding aerobic and anaerobic logic networks. Five genes were identified to be putative key components of the two energy metabolisms. Furthermore, community analysis using the Newman fast algorithm revealed two significant communities for the aerobic but only one for the anaerobic network. David Gene Functional Classification suggests that, under aerobic conditions, one such community reflects the cell cycle and cell replication, while the other one is linked to the mitochondrial respiratory chain function. PMID- 26839583 TI - Disposable screen printed sensor for the electrochemical detection of methamphetamine in undiluted saliva. AB - BACKGROUND: Methamphetamine has an adverse effect on the ability to drive safely. Police need to quickly screen potentially impaired drivers therefore a rapid disposable test for methamphetamine is highly desirable. This is the first proof of-concept report of a disposable electrochemical test for methamphetamine in undiluted saliva. RESULTS: A screen printed carbon electrode is used for the N,N' (1,4-phenylene)-dibenzenesulfonamide mediated detection of methamphetamine in saliva buffer and saliva. The oxidized mediator reacts with methamphetamine to give an electrochemically active adduct which can undergo electrochemical reduction. Galvanostatic oxidation in combination with a double square wave reduction technique resulted in detection of methamphetamine in undiluted saliva with a response time of 55 s and lower detection limit of 400 ng/mL. CONCLUSIONS: Using a double square wave voltammetry technique, rapid detection of methamphetamine in undiluted saliva can be achieved, however there is significant donor variation in response and the detection limit is significantly higher than desired. Further optimization of the assay and sensor format is required to improve the detection limit and reduce donor effects. PMID- 26839584 TI - A comprehensive understanding of the chemical vapour deposition of cadmium chalcogenides using Cd[(C6H5)2PSSe]2 single-source precursor: a density functional theory approach. AB - BACKGROUND: The phosphinato complexes of group IIB are of great interest for their potential toward technological applications. A gas phase mechanistic investigation of the chemical vapour deposition of cadmium chalcogenides from the decomposition of Cd[(C6H5)2PSSe]2, as a single source precursor is carried out and reported herein within the framework of density functional theory at the M06/LACVP* level of theory. RESULTS: The results reveal that the activation barriers and the product stabilities on the singlet potential energy surface (PES) favour CdS decomposition pathways, respectively. However, on the doublet PES, the activation barriers favour CdS while the product stabilities favour CdSe decomposition pathways, respectively. Contrary to the previously reported theoretical result for Cd[( (i) Pr)2PSSe]2, CdSe decomposition pathways were found to be the major pathways on both the singlet and the doublet PESs, respectively. CONCLUSION: Exploration of the complex gas phase mechanism and a detailed identification of the reaction intermediates enable us to understand and optimise selective growth process that occur in a chemical vapour deposition.Graphical abstractStructure of Cd[(C6H5)2PSSe]2 single-source precursor. PMID- 26839585 TI - End-to-end automated microfluidic platform for synthetic biology: from design to functional analysis. AB - BACKGROUND: Synthetic biology aims to engineer biological systems for desired behaviors. The construction of these systems can be complex, often requiring genetic reprogramming, extensive de novo DNA synthesis, and functional screening. RESULTS: Herein, we present a programmable, multipurpose microfluidic platform and associated software and apply the platform to major steps of the synthetic biology research cycle: design, construction, testing, and analysis. We show the platform's capabilities for multiple automated DNA assembly methods, including a new method for Isothermal Hierarchical DNA Construction, and for Escherichia coli and Saccharomyces cerevisiae transformation. The platform enables the automated control of cellular growth, gene expression induction, and proteogenic and metabolic output analysis. CONCLUSIONS: Taken together, we demonstrate the microfluidic platform's potential to provide end-to-end solutions for synthetic biology research, from design to functional analysis. PMID- 26839586 TI - Construction of a restriction-less, marker-less mutant useful for functional genomic and metabolic engineering of the biofuel producer Clostridium acetobutylicum. AB - BACKGROUND: Clostridium acetobutylicum is a gram-positive, spore-forming, anaerobic bacterium capable of converting various sugars and polysaccharides into solvents (acetone, butanol, and ethanol). The sequencing of its genome has prompted new approaches to genetic analysis, functional genomics, and metabolic engineering to develop industrial strains for the production of biofuels and bulk chemicals. RESULTS: The method used in this paper to knock-out or knock-in genes in C. acetobutylicum combines the use of an antibiotic-resistance gene for the deletion or replacement of the target gene, the subsequent elimination of the antibiotic-resistance gene with the flippase recombinase system from Saccharomyces cerevisiae, and a C. acetobutylicum strain that lacks upp, which encodes uracil phosphoribosyl-transferase, for subsequent use as a counter selectable marker. A replicative vector containing (1) a pIMP13 origin of replication from Bacillus subtilis that is functional in Clostridia, (2) a replacement cassette consisting of an antibiotic resistance gene (MLS (R) ) flanked by two FRT sequences, and (3) two sequences homologous to selected regions around target DNA sequence was first constructed. This vector was successfully used to consecutively delete the Cac824I restriction endonuclease encoding gene (CA_C1502) and the upp gene (CA_C2879) in the C. acetobutylicum ATCC824 chromosome. The resulting C. acetobutylicum Deltacac1502Deltaupp strain is marker-less, readily transformable without any previous plasmid methylation and can serve as the host for the "marker-less" genetic exchange system. The third gene, CA_C3535, shown in this study to encode for a type II restriction enzyme (Cac824II) that recognizes the CTGAAG sequence, was deleted using an upp/5 FU counter-selection strategy to improve the efficiency of the method. The restriction-less marker-less strain and the method was successfully used to delete two genes (ctfAB) on the pSOL1 megaplasmid and one gene (ldhA) on the chromosome to get strains no longer producing acetone or l-lactate. CONCLUSIONS: The restriction-less, marker-less strain described in this study, as well as the maker-less genetic exchange coupled with positive selection, will be useful for functional genomic studies and for the development of industrial strains for the production of biofuels and bulk chemicals. PMID- 26839587 TI - Engineering acyl carrier protein to enhance production of shortened fatty acids. AB - BACKGROUND: The acyl carrier protein (ACP) is an essential and ubiquitous component of microbial synthesis of fatty acids, the natural precursor to biofuels. Natural fatty acids usually contain long chains of 16 or more carbon atoms. Shorter carbon chains, with increased fuel volatility, are desired for internal combustion engines. Engineering the length specificity of key proteins in fatty acid metabolism, such as ACP, may enable microbial synthesis of these shorter chain fatty acids. RESULTS: We constructed a homology model of the Synechococcus elongatus ACP, showing a hydrophobic pocket harboring the growing acyl chain. Amino acids within the pocket were mutated to increase steric hindrance to the acyl chain. Certain mutant ACPs, when over-expressed in Escherichia coli, increased the proportion of shorter chain lipids; I75 W and I75Y showed the strongest effects. Expression of I75 W and I75Y mutant ACPs also increased production of lauric acid in E. coli that expressed the C12-specific acyl-ACP thioesterase from Cuphea palustris. CONCLUSIONS: We engineered the specificity of the ACP, an essential protein of fatty acid metabolism, to alter the E. coli lipid pool and enhance production of medium-chain fatty acids as biofuel precursors. These results indicate that modification of ACP itself could be combined with enzymes affecting length specificity in fatty acid synthesis to enhance production of commodity chemicals based on fatty acids. PMID- 26839588 TI - Genomic and secretomic insight into lignocellulolytic system of an endophytic bacterium Pantoea ananatis Sd-1. AB - BACKGROUND: Exploring microorganisms especially bacteria associated with the degradation of lignocellulosic biomass shows great potentials in biofuels production. The rice endophytic bacterium Pantoea ananatis Sd-1 with strong lignocellulose degradation capacity has been reported in our previous study. However, a comprehensive analysis of its corresponding degradative system has not yet been conducted. The aim of this work is to identify and characterize the lignocellulolytic enzymes of the bacterium to understand its mechanism of lignocellulose degradation and facilitate its application in sustainable energy production. RESULTS: The genomic analysis revealed that there are 154 genes encoding putative carbohydrate-active enzymes (CAZy) in P. ananatis Sd-1. This number is higher than that of compared cellulolytic and ligninolytic bacteria as well as other eight P. ananatis strains. The CAZy in P. ananatis Sd-1 contains a complete repertoire of enzymes required for cellulose and hemicellulose degradation. In addition, P. ananatis Sd-1 also possesses plenty of genes encoding potential ligninolytic relevant enzymes, such as multicopper oxidase, catalase/hydroperoxidase, glutathione S-transferase, and quinone oxidoreductase. Quantitative real-time PCR analysis of parts of genes encoding lignocellulolytic enzymes revealed that they were significantly up-regulated (at least P < 0.05) in presence of rice straw. Further identification of secretome of P. ananatis Sd-1 by nano liquid chromatography-tandem mass spectrometry confirmed that considerable amounts of proteins involved in lignocellulose degradation were only detected in rice straw cultures. Rice straw saccharification levels by the secretome of P. ananatis Sd-1 reached 129.11 +/- 2.7 mg/gds. Correspondingly, the assay of several lignocellulolytic enzymes including endoglucanase, exoglucanase, beta-glucosidase, xylanase-like, lignin peroxidase-like, and laccase-like activities showed that these enzymes were more active in rice straw relative to glucose substrates. The high enzymes activities were not attributed to bacterial cell densities but to the difference of secreted protein contents. CONCLUSION: Our results indicate that P. ananatis Sd-1 can produce considerable lignocellulolytic enzymes including cellulases, hemicellulases, and ligninolytic relevant enzymes. The high activities of those enzymes could be efficiently induced by lignocellulosic biomass. This identified degradative system is valuable for the lignocellulosic bioenergy industry. PMID- 26839589 TI - Metagenomic analysis and functional characterization of the biogas microbiome using high throughput shotgun sequencing and a novel binning strategy. AB - BACKGROUND: Biogas production is an economically attractive technology that has gained momentum worldwide over the past years. Biogas is produced by a biologically mediated process, widely known as "anaerobic digestion." This process is performed by a specialized and complex microbial community, in which different members have distinct roles in the establishment of a collective organization. Deciphering the complex microbial community engaged in this process is interesting both for unraveling the network of bacterial interactions and for applicability potential to the derived knowledge. RESULTS: In this study, we dissect the bioma involved in anaerobic digestion by means of high throughput Illumina sequencing (~51 gigabases of sequence data), disclosing nearly one million genes and extracting 106 microbial genomes by a novel strategy combining two binning processes. Microbial phylogeny and putative taxonomy performed using >400 proteins revealed that the biogas community is a trove of new species. A new approach based on functional properties as per network representation was developed to assign roles to the microbial species. The organization of the anaerobic digestion microbiome is resembled by a funnel concept, in which the microbial consortium presents a progressive functional specialization while reaching the final step of the process (i.e., methanogenesis). Key microbial genomes encoding enzymes involved in specific metabolic pathways, such as carbohydrates utilization, fatty acids degradation, amino acids fermentation, and syntrophic acetate oxidation, were identified. Additionally, the analysis identified a new uncultured archaeon that was putatively related to Methanomassiliicoccales but surprisingly having a methylotrophic methanogenic pathway. CONCLUSION: This study is a pioneer research on the phylogenetic and functional characterization of the microbial community populating biogas reactors. By applying for the first time high-throughput sequencing and a novel binning strategy, the identified genes were anchored to single genomes providing a clear understanding of their metabolic pathways and highlighting their involvement in anaerobic digestion. The overall research established a reference catalog of biogas microbial genomes that will greatly simplify future genomic studies. PMID- 26839590 TI - Organosolv pretreatment of sorghum bagasse using a low concentration of hydrophobic solvents such as 1-butanol or 1-pentanol. AB - BACKGROUND: The primary components of lignocellulosic biomass such as sorghum bagasse are cellulose, hemicellulose, and lignin. Each component can be utilized as a sustainable resource for producing biofuels and bio-based products. However, due to their complicated structures, fractionation of lignocellulosic biomass components is required. Organosolv pretreatment is an attractive method for this purpose. However, as organosolv pretreatment uses high concentrations of organic solvents (>50 %), decreasing the concentration necessary for fractionation would help reduce processing costs. In this study, we sought to identify organic solvents capable of efficiently fractionating sorghum bagasse components at low concentrations. RESULTS: Five alcohols (ethanol, 1-propanol, 2-propanol, 1 butanol, and 1-pentanol) were used for organosolv pretreatment of sorghum bagasse at a concentration of 12.5 %. Sulfuric acid (1 %) was used as a catalyst. With 1 butanol and 1-pentanol, three fractions (black liquor, liquid fraction containing xylose, and cellulose-enriched solid fraction) were obtained after pretreatment. Two-dimensional nuclear magnetic resonance analysis revealed that the lignin aromatic components of raw sorghum bagasse were concentrated in the black liquor fraction, although the major lignin side-chain (beta-O-4 linkage) was lost. Pretreatment with 1-butanol or 1-pentanol effectively removed p-coumarate, some guaiacyl, and syringyl. Compared with using no solvent, pretreatment with 1 butanol or 1-pentanol resulted in two-fold greater ethanol production from the solid fraction by Saccharomyces cerevisiae. CONCLUSIONS: Our results revealed that a low concentration (12.5 %) of a highly hydrophobic solvent such as 1 butanol or 1-pentanol can be used to separate the black liquor from the solid and liquid fractions. The efficient delignification and visible separation of the lignin-rich fraction possible with this method simplify the fractionation of sorghum bagasse. PMID- 26839591 TI - Succinic acid production on xylose-enriched biorefinery streams by Actinobacillus succinogenes in batch fermentation. AB - BACKGROUND: Co-production of chemicals from lignocellulosic biomass alongside fuels holds promise for improving the economic outlook of integrated biorefineries. In current biochemical conversion processes that use thermochemical pretreatment and enzymatic hydrolysis, fractionation of hemicellulose-derived and cellulose-derived sugar streams is possible using hydrothermal or dilute acid pretreatment (DAP), which then offers a route to parallel trains for fuel and chemical production from xylose- and glucose enriched streams. Succinic acid (SA) is a co-product of particular interest in biorefineries because it could potentially displace petroleum-derived chemicals and polymer precursors for myriad applications. However, SA production from biomass-derived hydrolysates has not yet been fully explored or developed. RESULTS: Here, we employ Actinobacillus succinogenes 130Z to produce succinate in batch fermentations from various substrates including (1) pure sugars to quantify substrate inhibition, (2) from mock hydrolysates similar to those from DAP containing single putative inhibitors, and (3) using the hydrolysate derived from two pilot-scale pretreatments: first, a mild alkaline wash (deacetylation) followed by DAP, and secondly a single DAP step, both with corn stover. These latter streams are both rich in xylose and contain different levels of inhibitors such as acetate, sugar dehydration products (furfural, 5-hydroxymethylfurfural), and lignin-derived products (ferulate, p-coumarate). In batch fermentations, we quantify succinate and co-product (acetate and formate) titers as well as succinate yields and productivities. We demonstrate yields of 0.74 g succinate/g sugars and 42.8 g/L succinate from deacetylated DAP hydrolysate, achieving maximum productivities of up to 1.27 g/L-h. Moreover, A. succinogenes is shown to detoxify furfural via reduction to furfuryl alcohol, although an initial lag in succinate production is observed when furans are present. Acetate seems to be the main inhibitor for this bacterium present in biomass hydrolysates. CONCLUSION: Overall, these results demonstrate that biomass-derived, xylose-enriched hydrolysates result in similar yields and titers but lower productivities compared to clean sugar streams, which can likely be improved via fermentation process developments and metabolic engineering. Overall, this study comprehensively examines the behavior of A. succinogenes on xylose-enriched hydrolysates on an industrially relevant, lignocellulosic feedstock, which will pave the way for future work toward eventual SA production in an integrated biorefinery. PMID- 26839592 TI - Balloon-guided inflation osteoplasty in the treatment of Hill-Sachs lesions of the humeral head: case report of a new technique. AB - BACKGROUND: The use of the extra-vertebral balloon osteoplasty is increasing and in the meanwhile it has become a safe surgical technique in the treatment of tibial head, distal radius and calcaneus fractures. In addition, we already could show in a biomechanical setup that the balloon osteoplasty might be a safe tool for reduction in the treatment of Hill-Sachs lesions, but clinical application has not been performed so far. CASE PRESENTATION: We report the case of a 53 year old male patient who was referred to our Trauma department (level I trauma center) after the first manifestation of a posterior shoulder dislocation due to an epileptic seizure, originated in a- up to this date unknown -glioblastoma. After closed reduction of the dislocated shoulder the X-ray showed a subcapital fracture of the proximal humerus with a large reversed Hill-Sachs lesion. We performed an open surgery via a deltoideopectoral approach and balloon osteoplasty was used to reduce the impression fracture (Hill-Sachs lesion) before fixing the fracture with a locking plate. In the post-operative CT scan we could show an anatomical reduction of the Hill-Sachs lesion. At the follow-up examination one year after surgery the patient reached full range of motion and stated no re-dislocation of the shoulder nor instability or pain. CONCLUSION: The reduction of an impressed humeral head fracture by use of balloon osteoplasty is a safe technique. This technique could be a new option in the treatment of Hill Sachs lesions and might be an alternative to well known standard procedures like the remplissage or tendon transfers without affecting rotation. PMID- 26839593 TI - Preferential Y-Y pairing and synapsis and abnormal meiotic recombination in a 47,XYY man with non obstructive azoospermia. AB - BACK GROUND: Men with 47, XYY syndrome are presented with varying physical attributes and degrees of infertility. Little information has been documented regarding the meiotic progression in patients with extra Y chromosome along with the synapses and recombination between the two Y chromosomes. METHODS: Spermatocyte spreading and immunostaining were applied to study the behavior of the extra Y chromosome during meiosis I in an azoospermia patient with 47, XYY syndrome and results were compared with five healthy controls with proven fertility. RESULTS: The extra Y chromosome was present in all the studied spermatocytes of the patient and preferentially paired and synapsed with the other Y chromosome. Consistently, gamma-H2AX staining completely disappeared from the synapsed regions of Y chromosomes. More interestingly, besides recombination on short arms, recombination on the long arms of Y chromosomes was also observed. No pairing and synapsis defects between homologous autosomes were detected, while significantly reduced recombination frequencies on autosomes were observed in the patient. The meiotic prophase I progression was disturbed with significantly increased proportion of leptotene, zygotene cells and decreased pachytene spermatocytes in the patient when compared with the controls. CONCLUSIONS: These findings highlight the importance of studies on meiotic behaviors in patients with an abnormal chromosomal constitution and provide an important framework for future studies, which may elucidate the impairment caused by extra Y chromosome in mammalian meiosis and fertility. PMID- 26839594 TI - r2VIM: A new variable selection method for random forests in genome-wide association studies. AB - BACKGROUND: Machine learning methods and in particular random forests (RFs) are a promising alternative to standard single SNP analyses in genome-wide association studies (GWAS). RFs provide variable importance measures (VIMs) to rank SNPs according to their predictive power. However, in contrast to the established genome-wide significance threshold, no clear criteria exist to determine how many SNPs should be selected for downstream analyses. RESULTS: We propose a new variable selection approach, recurrent relative variable importance measure (r2VIM). Importance values are calculated relative to an observed minimal importance score for several runs of RF and only SNPs with large relative VIMs in all of the runs are selected as important. Evaluations on simulated GWAS data show that the new method controls the number of false-positives under the null hypothesis. Under a simple alternative hypothesis with several independent main effects it is only slightly less powerful than logistic regression. In an experimental GWAS data set, the same strong signal is identified while the approach selects none of the SNPs in an underpowered GWAS. CONCLUSIONS: The novel variable selection method r2VIM is a promising extension to standard RF for objectively selecting relevant SNPs in GWAS while controlling the number of false positive results. PMID- 26839596 TI - Increased dosage of infliximab is a potential cause of Pneumocystis carinii pneumonia. AB - METHODS: Pneumocystis carinii pneumonia occasionally appears in immunodeficient patients. While several reports have shown that Pneumocystis carinii pneumonia occurred in the early phase of starting infliximab treatment in patients with Crohn's disease (CD), the present case suggests for the first time that an increased dosage of infliximab may also lead to pneumonia. RESULTS: A 51-year-old male had been taking 5 mg of infliximab for the treatment of CD for 10 years with no adverse events. Beginning in September 2013, the dose of infliximab had to be increased to 10 mg/kg because his status worsened. Thereafter, he complained of a fever and cough, and a CT scan revealed ground-glass opacities in the lower lobes of the bilateral lung with a crazy-paving pattern. Bronchoscopy detected swelling of the tracheal mucosa with obvious dilations of the vessels. A polymerase chain reaction using a bronchoalveolar lavage fluid sample detected specific sequences for Pneumocystis jirovecii; thus he was diagnosed with Pneumocystis carinii (jirovecii) pneumonia. After discontinuing infliximab and starting antibiotic treatment, his symptoms and CT findings were dramatically improved. CONCLUSIONS: The administration of an increased dosage of infliximab can cause Pneumocystis carinii pneumonia in CD patients. PMID- 26839597 TI - Fragmentation trees reloaded. AB - BACKGROUND: Untargeted metabolomics commonly uses liquid chromatography mass spectrometry to measure abundances of metabolites; subsequent tandem mass spectrometry is used to derive information about individual compounds. One of the bottlenecks in this experimental setup is the interpretation of fragmentation spectra to accurately and efficiently identify compounds. Fragmentation trees have become a powerful tool for the interpretation of tandem mass spectrometry data of small molecules. These trees are determined from the data using combinatorial optimization, and aim at explaining the experimental data via fragmentation cascades. Fragmentation tree computation does not require spectral or structural databases. To obtain biochemically meaningful trees, one needs an elaborate optimization function (scoring). RESULTS: We present a new scoring for computing fragmentation trees, transforming the combinatorial optimization into a Maximum A Posteriori estimator. We demonstrate the superiority of the new scoring for two tasks: both for the de novo identification of molecular formulas of unknown compounds, and for searching a database for structurally similar compounds, our method SIRIUS 3, performs significantly better than the previous version of our method, as well as other methods for this task. CONCLUSION: SIRIUS 3 can be a part of an untargeted metabolomics workflow, allowing researchers to investigate unknowns using automated computational methods.Graphical abstractWe present a new scoring for computing fragmentation trees from tandem mass spectrometry data based on Bayesian statistics. The best scoring fragmentation tree most likely explains the molecular formula of the measured parent ion. PMID- 26839598 TI - ADMET evaluation in drug discovery: 15. Accurate prediction of rat oral acute toxicity using relevance vector machine and consensus modeling. AB - BACKGROUND: Determination of acute toxicity, expressed as median lethal dose (LD50), is one of the most important steps in drug discovery pipeline. Because in vivo assays for oral acute toxicity in mammals are time-consuming and costly, there is thus an urgent need to develop in silico prediction models of oral acute toxicity. RESULTS: In this study, based on a comprehensive data set containing 7314 diverse chemicals with rat oral LD50 values, relevance vector machine (RVM) technique was employed to build the regression models for the prediction of oral acute toxicity in rate, which were compared with those built using other six machine learning approaches, including k-nearest-neighbor regression, random forest (RF), support vector machine, local approximate Gaussian process, multilayer perceptron ensemble, and eXtreme gradient boosting. A subset of the original molecular descriptors and structural fingerprints (PubChem or SubFP) was chosen by the Chi squared statistics. The prediction capabilities of individual QSAR models, measured by q ext (2) for the test set containing 2376 molecules, ranged from 0.572 to 0.659. CONCLUSION: Considering the overall prediction accuracy for the test set, RVM with Laplacian kernel and RF were recommended to build in silico models with better predictivity for rat oral acute toxicity. By combining the predictions from individual models, four consensus models were developed, yielding better prediction capabilities for the test set (q ext (2) = 0.669-0.689). Finally, some essential descriptors and substructures relevant to oral acute toxicity were identified and analyzed, and they may be served as property or substructure alerts to avoid toxicity. We believe that the best consensus model with high prediction accuracy can be used as a reliable virtual screening tool to filter out compounds with high rat oral acute toxicity. Graphical abstractWorkflow of combinatorial QSAR modelling to predict rat oral acute toxicity. PMID- 26839599 TI - The influences of nitric oxide, epinephrine, and dopamine on vascular tone: dose response modeling and simulations. AB - INTRODUCTION: Sodium Nitroprusside has successfully been an excellent choice when considering a decrease in systemic vascular resistance in the critical care setting. However, reflex tachycardia and ventilation-perfusion mismatch are possible side effects of this agent. To maintaining cardiac output, cerebral perfusion pressure, and concurrently drop SVR, low-dose epinephrine or dopamine are viable options. The aim of this paper is to conduct dose-response simulations to identify the equivalent dopamine, epinephrine, and nitroprusside infusion doses to decrease the systemic vascular resistance by 20% and by 40% from baseline resting values. METHODS: Three studies were identified in the literature with reported epinephrine, dopamine, and sodium nitroprusside infusion doses with corresponding systemic vascular resistance responses. Infusion doses were normalized to mcg/kg/min and SVR values were normalized and scaled to the percent decrease (%SVR) in SVR from baseline resting values. The original published studies were mathematically modeled and the Hill equation parameters used for further dose-response simulations of a virtual population. One-hundred patients were simulated various doses resulting in corresponding %SVR responses for each of the three drugs. RESULTS: Equivalent infusion doses achieving in an approximate 20-25% decrease in SVR, from baseline, were identified for epinephrine, dopamine, and sodium nitroprusside. Moreover, equivalent infusion doses were identified for epinephrine and nitroprusside to decrease the SVR by 40% from baseline. CONCLUSION: Even though sodium nitroprusside is traditionally used in decreasing SVR, low doses of dopamine or epinephrine are viable alternatives to patients with contraindications to nitroprusside infusions or who will require prolonged infusions to avoid toxicity. The multiple comparisons procedure-modeling approach is an excellent methodology for dose-finding exercises and has enabled identification of equivalent pharmacodynamic responses for epinephrine, dopamine, and sodium nitroprusside through mathematic simulations. PMID- 26839601 TI - Kinesiological Analysis of Stationary Running Performed in Aquatic and Dry Land Environments. AB - The purpose of the present study was to analyze the electromyographic (EMG) signals of the rectus femoris (RF), vastus lateralis (VL), semitendinosus (ST) and short head of the biceps femoris (BF) during the performance of stationary running at different intensities in aquatic and dry land environments. The sample consisted of 12 female volunteers who performed the stationary running exercise in aquatic and dry land environments at a submaximal cadence (80 beats.min(-1) controlled by a metronome) and at maximal velocity, with EMG signal measurements from the RF, VL, ST and BF muscles. The results showed a distinct pattern between environments for each muscle examined. For the submaximal cadence of 80 beats.min(-1), there was a reduced magnitude of the EMG signal in the aquatic environment, except for the ST muscle, the pattern of which was similar in both environments. In contrast to the submaximal cadence, the pattern of the EMG signal from all of the muscles showed similar magnitudes for both environments and phases of movement at maximal velocity, except for the VL muscle. Therefore, the EMG signals from the RF, VL, ST and BF muscles of women during stationary running had different patterns of activation over the range of motion between aquatic and dry land environments for different intensities. Moreover, the neuromuscular responses of the lower limbs were optimized by an increase in intensity from submaximal cadence to maximal velocity. PMID- 26839600 TI - H3K4 tri-methylation breadth at transcription start sites impacts the transcriptome of systemic lupus erythematosus. AB - BACKGROUND: The autoimmune disease systemic lupus erythematosus (SLE) has a modified epigenome with modified tri-methylation of histone H3 lysine 4 (H3K4me3) at specific loci across the genome. H3K4me3 is a canonical chromatin mark of active transcription. Recent studies have suggested that H3K4me3 breadth has an important regulatory role in cell identity. This project examined H3K4me3 breadth at transcription start sites (TSS) in primary monocytes and its association with differential gene transcription in SLE. RESULTS: Integrative analysis was applied to chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA seq) data generated from primary monocytes as well as genomic data available in public repositories. Four distinctive H3K4me3 patterns of ChIP-seq peaks were identified at 8399 TSSs. Narrow peaks were highly enriched with genes related to housekeeping functions. The broader peaks with extended H3K4me3 immediately upstream and/or downstream of TSS were associated with immune response genes. Many TSSs had downstream H3K4me3 extended to ~650 bp, where the transition of H3K4me3 to H3K36me3, a transcriptional elongation mark, is often found. The H3K4me3 pattern was strongly associated with transcription in SLE. Genes with narrow peaks were less likely (OR = 0.14, p = 2 * 10(-4)) while genes with extended downstream H3K4me3 were more likely (OR = 2.37, p = 1 * 10(-11)) to be overexpressed in SLE. Of the genes significantly overexpressed in SLE, 78.8 % had increased downstream H3K4me3 while only 47.1 % had increased upstream H3K4me3. Gene transcription sensitively and consistently responded to H3K4me3 change downstream of TSSs. Every 1 % increase of H3K4me3 in this region leads to ~1.5 % average increase of transcription. CONCLUSIONS: We identified the immediate TSS downstream nucleosome as a crucial regulator responsible for transcription changes in SLE. This study applied a unique method to study the effect of H3K4me3 breadth on diseases and revealed new insights about epigenetic modifications in SLE, which could lead to novel treatments. PMID- 26839603 TI - Multilevel Models for the Analysis of Angle-Specific Torque Curves with Application to Master Athletes. AB - The aim of this paper was to outline a multilevel modeling approach to fit individual angle-specific torque curves describing concentric knee extension and flexion isokinetic muscular actions in Master athletes. The potential of the analytical approach to examine between individual differences across the angle specific torque curves was illustrated including between-individuals variation due to gender differences at a higher level. Torques in concentric muscular actions of knee extension and knee extension at 60o.s(-1) were considered within a range of motion between 5o and 85o (only torques "truly" isokinetic). Multilevel time series models with autoregressive covariance structures with standard multilevel models were superior fits compared with standard multilevel models for repeated measures to fit angle-specific torque curves. Third and fourth order polynomial models were the best fits to describe angle-specific torque curves of isokinetic knee flexion and extension concentric actions, respectively. The fixed exponents allow interpretations for initial acceleration, the angle at peak torque and the decrement of torque after peak torque. Also, the multilevel models were flexible to illustrate the influence of gender differences on the shape of torque throughout the range of motion and in the shape of the curves. The presented multilevel regression models may afford a general framework to examine angle-specific moment curves by isokinetic dynamometry, and add to the understanding mechanisms of strength development, particularly the force-length relationship, both related to performance and injury prevention. PMID- 26839602 TI - Kinematic Adaptations of Forward And Backward Walking on Land and in Water. AB - The aim of this study was to compare sagittal plane lower limb kinematics during walking on land and submerged to the hip in water. Eight healthy adults (age 22.1 +/- 1.1 years, body height 174.8 +/- 7.1 cm, body mass 63.4 +/- 6.2 kg) were asked to cover a distance of 10 m at comfortable speed with controlled step frequency, walking forward or backward. Sagittal plane lower limb kinematics were obtained from three dimensional video analysis to compare spatiotemporal gait parameters and joint angles at selected events using two-way repeated measures ANOVA. Key findings were a reduced walking speed, stride length, step length and a support phase in water, and step length asymmetry was higher compared to the land condition (p<0.05). At initial contact, knees and hips were more flexed during walking forward in water, whilst, ankles were more dorsiflexed during walking backward in water. At final stance, knees and ankles were more flexed during forward walking, whilst the hip was more flexed during backward walking. These results show how walking in water differs from walking on land, and provide valuable insights into the development and prescription of rehabilitation and training programs. PMID- 26839604 TI - Effect of The Swimmer's Head Position on Passive Drag. AB - The aim of this study was to investigate the effect of the head position on passive drag with a towing-line experiment in a swimming pool. The tests were performed on ten male swimmers with regional level swimming skills and at least 10 years of competitive swimming experience. They were towed underwater (at a depth of 60 cm) at three speeds (1.5, 1.7 and 1.9 m/s) and in two body positions (arms above the swimmer's head and arms alongside the body). These two body positions were repeated while the swimmer's head was positioned in three different ways: head-up, head-middle and head-down in relation to the body's horizontal alignment. The results showed a reduction of 4-5.2% in the average passive drag at all speeds when the head was down or aligned to the swimmer's arms alongside the body, in comparison to the head-up position. A major significant decrease of 10.4-10.9% (p < 0.05) was shown when the head was down or aligned at the swimmer's arms above the swimmer's head. The passive drag tended to decrease significantly by a mean of 17.6% (p < 0.001) for all speeds examined with the arms alongside the body position rather than with the arms above the head position. The swimmer's head location may play an important role in reducing hydrodynamic resistance during passive underwater gliding. PMID- 26839605 TI - Scapula Kinematics of Youth Baseball Players. AB - Literature has revealed the importance of quantifying resting scapular posture in overhead athletes as well as quantifying scapular kinematics during dynamic movement. Prior to this project much of the attention in throwing research had been focused on the position of the humerus without description of the positioning of the scapula. Therefore, it was the purpose of this study to present scapular kinematics during pitching in youth baseball players. Twenty five youth baseball players (age 11.3 + 1.0 years; body height 152.4 + 9.0 cm; body mass 47.5 + 11.3 kg), with no history of injury, participated in the study. Scapular kinematics at the events of maximum humeral external rotation (MER) and maximum humeral internal rotation (MIR) during the pitching motion were assessed three-dimensionally while pitching fastballs for strikes. Results revealed that at the event of MER, the scapula was in a position of retraction, upward rotation and a posterior tilt. While at the event of MIR, the scapula was protracted, upward rotated and tilted anteriorly. PMID- 26839606 TI - Effects of Proprioceptive Neuromuscular Facilitation Stretching and Kinesiology Taping on Pelvic Compensation During Double-Knee Extension. AB - Shortened hamstrings are likely to restrict the anterior pelvic tilt and induce a slumped posture due to the posterior pelvic tilt. This study was conducted to compare the effects of proprioceptive neuromuscular facilitation (PNF) stretching and modified anterior pelvic tilt taping (APTT) on hamstring shortness-associated pelvic compensation while executing seated double-knee extension. Male college students (28 healthy young adults; mean age: 21.4 +/- 2.1 years) with hamstring shortness were recruited as study subjects and randomly assigned to either the PNF stretching group (control group) or the APTT group (experimental group). In all the subjects, changes in the movement distance of the centre of gluteal pressure (COGP) as well as rectus abdominis (RA) and semitendinosus (SEM) muscle activities were measured during seated double-knee extension while the respective intervention method was applied. Both groups showed significant decreases in COGP distance and RA muscle activity compared with their respective baseline values (p < 0.05), however, no significant changes were observed in SEM muscle activity. We can infer that not only a direct intervention on the hamstring, such as PNF stretching, but also a modified APTT-mediated pelvic intervention may be used as a method for reducing pelvic compensation induced by hamstring shortness. PMID- 26839607 TI - Interaction Between Leg Muscle Performance and Sprint Acceleration Kinematics. AB - This study investigated relationships between 10 m sprint acceleration, step kinematics (step length and frequency, contact and flight time), and leg muscle performance (power, stiffness, strength). Twenty-eight field sport athletes completed 10 m sprints that were timed and filmed. Velocity and step kinematics were measured for the 0-5, 5-10, and 0-10 m intervals to assess acceleration. Leg power was measured via countermovement jumps (CMJ), a five-bound test (5BT), and the reactive strength index (RSI) defined by 40 cm drop jumps. Leg stiffness was measured by bilateral and unilateral hopping. A three-repetition maximum squat determined strength. Pearson's correlations and stepwise regression (p <= 0.05) determined velocity, step kinematics, and leg muscle performance relationships. CMJ height correlated with and predicted velocity in all intervals (r = 0.40 0.54). The 5BT (5-10 and 0-10 m intervals) and RSI (5-10 m interval) also related to velocity (r = 0.37-0.47). Leg stiffness did not correlate with acceleration kinematics. Greater leg strength related to and predicted lower 0-5 m flight times (r = -0.46 to -0.51), and a longer 0-10 m step length (r = 0.38). Although results supported research emphasizing the value of leg power and strength for acceleration, the correlations and predictive relationships (r(2) = 0.14-0.29) tended to be low, which highlights the complex interaction between sprint technique and leg muscle performance. Nonetheless, given the established relationships between speed, leg power and strength, strength and conditioning coaches should ensure these qualities are expressed during acceleration in field sport athletes. PMID- 26839608 TI - Intra-Personal and Inter-Personal Kinetic Synergies During Jumping. AB - We explored synergies between two legs and two subjects during preparation for a long jump into a target. Synergies were expected during one-person jumping. No such synergies were expected between two persons jumping in parallel without additional contact, while synergies were expected to emerge with haptic contact and become stronger with strong mechanical contact. Subjects performed jumps either alone (each foot standing on a separate force platform) or in dyads (parallel to each other, each person standing on a separate force platform) without any contact, with haptic contact, and with strong coupling. Strong negative correlations between pairs of force variables (strong synergies) were seen in the vertical force in one-person jumps and weaker synergies in two-person jumps with the strong contact. For other force variables, only weak synergies were present in one-person jumps and no negative correlations between pairs of force variable for two-person jumps. Pairs of moment variables from the two force platforms at steady state showed positive correlations, which were strong in one person jumps and weaker, but still significant, in two-person jumps with the haptic and strong contact. Anticipatory synergy adjustments prior to action initiation were observed in one-person trials only. We interpret the different results for the force and moment variables at steady state as reflections of postural sway. PMID- 26839609 TI - Changes in Respiratory Parameters and Fin-Swimming Performance Following a 16 Week Training Period with Intermittent Breath Holding. AB - The purpose of this study was to examine the effects of training with intermittent breath holding (IBH) on respiratory parameters, arterial oxygen saturation (SpO2) and performance. Twenty-eight fin-swimming athletes were randomly divided into two groups and followed the same training for 16 weeks. About 40% of the distance of each session was performed with self-selected breathing frequency (SBF group) or IBH (IBH group). Performance time of 50 and 400 m at maximum intensity was recorded and forced expired volume in 1 s (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF) and SpO2 were measured before and after the 50 m test at baseline and post-training. Post-training, the respiratory parameters were increased in the IBH but remained unchanged in the SBF group (FEV1: 17 +/-15% vs. -1 +/-11%; FVC: 22 +/-13% vs. 1 +/-10%; PEF: 9 +/ 14% vs. -4 +/-15%; p<0.05). Pre compared to post-training SpO2 was unchanged at baseline and decreased post-training following the 50 m test in both groups (p<0.05). The reduction was higher in the IBH compared to the SBF group (p<0.05). Performance in the 50 and 400 m tests improved in both groups, however, the improvement was greater in the IBH compared to the SBF group in both 50 and 400 m tests (p<0.05). The use of IBH is likely to enhance the load on the respiratory muscles, thus, contributing to improvement of the respiratory parameters. Decreased SpO2 after IBH is likely due to adaptation to hypoventilation. IBH favours performance improvement at 50 and 400 m fin-swimming. PMID- 26839610 TI - Rating of Perceived Exertion and Physiological Responses in Water-Based Exercise. AB - The aim of the present study was to relate the overall rating of perceived exertion (RPE-overall) with cardiorespiratory and neuromuscular variables during stationary running with the elbow flexion/extension performed with water-floating equipment. The sample consisted of eleven women that performed the water-based exercise at submaximal cadences. The heart rate, oxygen uptake, ventilation, and electromyographic signal (EMG) from biceps brachii (%EMG BB), triceps brachii (%EMG TB), biceps femoris (%EMG BF) and rectus femoris (%EMG RF) muscles were measured during the exercise, and the overall RPE was measured immediately following its completion. The Pearson product-moment linear correlation was used to investigate associations between the variables analyzed in the present study. Significant relationships were observed between the RPE-overall and all the cardiorespiratory variables, with the r values ranging from 0.60 to 0.70 (p<0.05). In addition, the RPE-overall showed a significant (p<0.05) relationship with %EMG BB (r=0.55) and %EMG BF (r=0.50). These results suggest an association between the RPE-overall with all cardiorespiratory and two neuromuscular variables during the execution of a water-based aerobic exercise using water floating equipment. PMID- 26839611 TI - Effects of Regular Recreational Exercise Training on Serum ANGPTL3-Like Protein and Lipid Profile in Young Healthy Adults. AB - Evidence of the role of ANGPTL3, a liver-secreted glycoprotein, in serum lipid turnover, led us to hypothesize that this protein may be involved in modification of the lipid profile induced by exercise-training. Given the lack of data regarding this issue, the main goal of the present study was to investigate the effects of regular participation in a recreational physical activity program on serum ANGPTL3 and selected lipid profile measures in young, apparently healthy female and male adults. We compared serum ANGPTL3, lipid profile measures, common lipid ratios, the Atherogenic Index of Plasma (AIP) and glucose in fasting blood samples derived from 22 active physical education students including active females (AF, N=6) and males (AM, N=16) with samples from 28 relatively sedentary age-matched peers, including female (SF, N=9) and male (SM, N=19) individuals not involved in any regular physical conditioning program. Despite high inter individual variability of serum ANGPTL3, there was a general tendency toward higher serum ANGPTL3 and HDL-C in women compared to men, but without significant differences related to their physical activity status. Based on both routine lipid profile measures and lipid ratios, all participants had normal lipid profiles, normal glycemia, as well as favorable anthropometric indices not suggesting increased cardiometabolic risk. However, lower levels of the TG/HDL-C ratio and AIP in physically active compared to relatively sedentary participants, reflecting the predominance of large, buoyant LDL particles, strongly support the view of beneficial health-promoting effects of regular participation in recreational sport activities. PMID- 26839613 TI - The Accumulative Effect of Concentric-Biased and Eccentric-Biased Exercise on Cardiorespiratory and Metabolic Responses to Subsequent Low-Intensity Exercise: A Preliminary Study. AB - The study investigated the accumulative effect of concentric-biased and eccentric biased exercise on cardiorespiratory, metabolic and neuromuscular responses to low-intensity exercise performed hours later. Fourteen young men cycled at low intensity (~60 rpm at 50% maximal oxygen uptake) for 10 min before, and 12 h after: concentric-biased, single-leg cycling exercise (CON) (performed ~19:30 h) and eccentric-biased, double-leg knee extension exercise (ECC) (~06:30 h the following morning). Respiratory measures were sampled breath-by-breath, with oxidation values derived from stoichiometry equations. Knee extensor neuromuscular function was assessed before and after CON and ECC. Cardiorespiratory responses during low-intensity cycling were unchanged by accumulative CON and ECC. The RER was lower during low-intensity exercise 12 h after CON and ECC (0.88 +/- 0.08), when compared to baseline (0.92 +/- 0.09; p = 0.02). Fat oxidation increased from baseline (0.24 +/- 0.2 g.min(-1)) to 12 h after CON and ECC (0.39 +/- 0.2 g.min(-1); p = 0.01). Carbohydrate oxidation decreased from baseline (1.59 +/- 0.4 g.min(-1)) to 12 h after CON and ECC (1.36 +/- 0.4 g.min(-1); p = 0.03). These were accompanied by knee extensor force loss (right leg: -11.6%, p < 0.001; left leg: -10.6%, p = 0.02) and muscle soreness (right leg: 2.5 +/- 0.9, p < 0.0001; left leg: 2.3 +/- 1.2, p < 0.01). Subsequent concentric-biased and eccentric-biased exercise led to increased fat oxidation and decreased carbohydrate oxidation, without impairing cardiorespiration, during low-intensity cycling. An accumulation of fatiguing and damaging exercise increases fat utilisation during low intensity exercise performed as little as 12 h later. PMID- 26839612 TI - Effect of Kinesiotape Applications on Ball Velocity and Accuracy in Amateur Soccer and Handball. AB - Evidence supporting performance enhancing effects of kinesiotape in sports is missing. The aims of this study were to evaluate effects of kinesiotape applications with regard to shooting and throwing performance in 26 amateur soccer and 32 handball players, and to further investigate if these effects were influenced by the players' level of performance. Ball speed as the primary outcome and accuracy of soccer kicks and handball throws were analyzed with and without kinesiotape by means of radar units and video recordings. The application of kinesiotapes significantly increased ball speed in soccer by 1.4 km/h (p=0.047) and accuracy with a lesser distance from the target by -6.9 cm (p=0.039). Ball velocity in handball throws also significantly increased by 1.2 km/h (p=0.013), while accuracy was deteriorated with a greater distance from the target by 3.4 cm (p=0.005). Larger effects with respect to ball speed were found in players with a lower performance level in kicking (1.7 km/h, p=0.028) and throwing (1.8 km/h, p=0.001) compared with higher level soccer and handball players (1.2 km/h, p=0.346 and 0.5 km/h, p=0.511, respectively). In conclusion, the applications of kinesiotape used in this study might have beneficial effects on performance in amateur soccer, but the gain in ball speed in handball is counteracted by a significant deterioration of accuracy. Subgroup analyses indicate that kinesiotape may yield larger effects on ball velocity in athletes with lower kicking and throwing skills. PMID- 26839614 TI - The Use of Thermal Imaging in the Evaluation of the Symmetry of Muscle Activity in Various Types of Exercises (Symmetrical and Asymmetrical). AB - In order to achieve higher efficiency of training and thus better athletic performance, new research and diagnostic methods are constantly being developed, particularly those that are non-invasive. One such a method is thermography, suitable for quantitative and therefore objective evaluation of variables, such as changes in the temperature of the skin covering working muscles. The aim of this study was to use a thermal imaging infrared camera to evaluate temperature changes of symmetric body surfaces over symmetrically working muscles of male scullers after exercising on a two-oared rowing ergometer and compare these to asymmetrically working muscles of handball players after an endurance training session containing elements of an actual game. In the scullers, the mean temperature of body surfaces was always lower post than pre exercise, with no significant differences in an average temperature drop between the opposite sides, indicating that the work of the muscles involved in the physical exertion on the rowing ergometer was symmetrical. In contrast, in the handball players, skin temperatures in symmetric areas over the asymmetrically working muscles showed statistically significant differences between sides, which was associated with the functional asymmetry of training. This study indicates that thermal imaging may be useful for coaches in the evaluation of technical preparations in sports in which equal involvement of symmetric muscles is a condition of success, e.g. in scullers. PMID- 26839615 TI - Changes in Endurance Performance in Young Athletes During Two Training Seasons. AB - The aim of the study was to assess changes in endurance performance in young runners (females and males) during two training seasons. It involved 19 male and 16 female athletes aged 15-17 specializing in track-and-field middle and long distances runs. The following parameters were measured three times during the training season: maximal oxygen uptake, running economy, and the level of the second ventilatory threshold. Training volume and intensity during each season were analyzed within an 8-week period prior to the exercise tests. The volume and intensity of training at various stages of preparation in both seasons were similar. During the first year of observation, significant improvements in relative volume of maximal oxygen uptake were reported both in female and male athletes. During the second training season, it was found that running economy improved both in women and men, with no changes in maximal oxygen uptake. The same (in terms of volume and intensity) endurance training carried out with young runners during two consecutive training seasons can result in different training effects. PMID- 26839617 TI - The Effect of Different Recovery Duration on Repeated Anaerobic Performance in Elite Cyclists. AB - This study investigated the effect of recovery duration on repeated anaerobic performance in elite cyclists. The study followed a cross-over design protocol. Twelve elite male cyclists were randomly assigned to three groups (with recovery duration of 1, 2 and 3 min, respectively). All the subjects performed 4 repeated Wingate tests (4 * 30 s WT) at 48 h intervals for three different recovery periods. No significant interaction was observed between the effects of recovery duration and repetition (p>0.05), whereas there was a significant main effect of repetition on peak power, mean power, and a fatigue index (p<0.05). Peak power decreased significantly in repeated WTs with 1 and with 2 min recovery duration (p<0.05), but it did not change significantly in a repeated WT with 3 min recovery (p>0.05). In contrast, mean power decreased significantly in repeated WTs with 1, 2 and 3 min recovery duration (p<0.05). The fatigue index increased significantly in a repeated WT with 1 min recovery duration (p<0.05), but no significant difference was observed in the fatigue index in repeated WTs with 2 and 3 min recovery (p>0.05). In a 4 * 30 s WT, peak power decreased in cycles with 1 and 2 min recovery duration, but remained unchanged with 3 min recovery duration, whereas mean power decreased in all recovery duration procedures. The WT with 1 min recovery duration caused greater fatigue. Although recovery duration affected both peak power and mean power, the effect on peak power was greater. PMID- 26839618 TI - Physiological Adaptations to Training in Competitive Swimming: A Systematic Review. AB - The purpose of this systematic review was to summarize longitudinal studies on swimming physiology and get implications for daily practice. A computerized search of databases according to the PRISMA statement was employed. Studies were screened for eligibility on inclusion criteria: (i) present two testing points; (ii) on swimming physiology; (iii) using adult elite swimmers; (iv) no case studies or with small sample sizes. Two independent reviewers used a checklist to assess the methodological quality of the studies. Thirty-four studies selected for analysis were gathered into five main categories: blood composition (n=7), endocrine secretion (n=11), muscle biochemistry (n=7), cardiovascular response (n=8) and the energetic profile (n=14). The mean quality index was 10.58 +/- 2.19 points demonstrating an almost perfect agreement between reviewers (K = 0.93). It can be concluded that the mixed findings in the literature are due to the diversity of the experimental designs. Micro variables obtained at the cellular or molecular level are sensitive measures and demonstrate overtraining signs and health symptoms. The improvement of macro variables (i.e. main physiological systems) is limited and may depend on the athletes' training background and experience. PMID- 26839619 TI - Knee Muscles Isokinetic Evaluation after a Six-Month Regular Combined Swim and Dry-Land Strength Training Period in Adolescent Competitive Swimmers. AB - Previous studies demonstrated significant increases in the shoulder internal rotators' peak torque values and unilateral muscular imbalances of the shoulder rotators after a competitive swim period. However, there are no similar data concerning the knee muscles. The purpose of the current study was to examine the effects of a six-month training period on knee flexor and extensor peak torque values, examine a possible bilateral strength deficit and evaluate the unilateral strength balance in competitive swimmers. Eleven male adolescent swimmers (age: 14.82 +/- 0.45 years) were tested for concentric knee extension and flexion peak torque (60 degrees /s) with an isokinetic dynamometer, before and after a regular combined swim and dry-land strength training period. A trend towards greater improvements in the knee extensor compared to flexor muscles peak torque was observed. Furthermore, the bilateral strength deficit remained almost unchanged, whereas unilateral strength imbalance was increased for both limbs. However, all results were non-significant (p > 0.05). According to the data presented, a six month regular combined swim and dry-land strength training period caused non significant alterations for all the parameters evaluated during isokinetic testing. This study highlights the fact that competitive adolescent swimmers demonstrated unilateral knee strength imbalances throughout a long period of their yearly training macrocycle. PMID- 26839616 TI - Central and Peripheral Fatigue During Resistance Exercise - A Critical Review. AB - Resistance exercise is a popular form of conditioning for numerous sport disciplines, and recently different modes of strength training are being evaluated for health benefits. Resistance exercise differs significantly in nature, and several variables determine the direction and range of adaptive changes that occur in the muscular and skeletal system of the body. Some modes of resistance training can also be effective in stimulating the cardiovascular system. These variables include exercise selection (general, specific, single or multi joint, dynamic, explosive), type of resistance (free weights, variable resistance, isokinetics), order of exercise (upper and lower body or push and pull exercises), and most of all the training load which includes intensity expressed as % of 1RM, number of repetitions, number of sets and the rest interval between sets. Manipulating these variables allows for specific adaptive changes which may include gains in muscle mass, muscle strength or muscle endurance. It has been well established that during resistance exercise fatigue occurs, regardless of the volume and intensity of work applied. The peripheral mechanisms of fatigue have been studied and explained in more detail than those related to the CNS. This review is an attempt to bring together the latest knowledge regarding fatigue, both peripheral and central, during resistance exercise. The authors of this review concentrated on physiological and biochemical mechanisms underlying fatigue in exercises performed with maximal intensity, as well as those performed to exhaustion with numerous repetitions and submaximal load. PMID- 26839620 TI - The Kinetic Specificity of Plyometric Training: Verbal Cues Revisited. AB - Plyometric training is a popular method utilized by strength and conditioning professionals to improve aspects of functional strength. The purpose of this study was to explore the influence of extrinsic verbal cueing on the specificity of jumping movements. Thirteen participants (age: 23.4 +/- 1.9 yr, body height: 170.3 +/- 15.1 cm, body mass: 70.3 +/- 23.8 kg,) performed four types of jumps: a depth jump "as quickly as possible" (DJT), a depth jump "as high as possible" (DJH), a countermovement jump (CMJ), and a squat jump (SJ). Dependent measures, which included measurement of strength and power, were acquired using a force platform. From the results, differences in body-weight normalized peak force (BW) (DJH: 4.3, DJT: 5.6, CMJ: 2.5, SJ: 2.2), time in upward propulsion (s) (DJH: 0.34, DJT: 0.20, CMJ: 0.40, SJ: 0.51), and mean acceleration (m.s-2) (DJH: 26.7, DJT: 36.2, CMJ: 19.8, SJ: 17.3) were observed across all comparisons (p = 0.001 - 0.033). Differences in the body-weight normalized propulsive impulse (BW.s) (DJH: 0.55, DJT: 0.52, CMJ: 0.39, SJ: 0.39) and propulsive power (kW) (DJH: 13.7, DJT: 16.5, CMJ: 11.5, SJ: 12.1) were observed across all comparisons (p = 0.001 - 0.050) except between the CMJ and SJ (p = 0.128 - 0.929). The results highlight key kinetic differences influencing the specificity of plyometric movements and suggest that verbal cues may be used to emphasize the development of reactive strength (e.g. DJT) or high-velocity concentric power (e.g. DJH). PMID- 26839621 TI - Acute Physiological and Thermoregulatory Responses to Extended Interval Training in Endurance Runners: Influence of Athletic Performance and Age. AB - This study aimed to describe the acute impact of extended interval training (EIT) on physiological and thermoregulatory levels, as well as to determine the influence of athletic performance and age effect on the aforementioned response in endurance runners. Thirty-one experienced recreational male endurance runners voluntarily participated in this study. Subjects performed EIT on an outdoor running track, which consisted of 12 runs of 400 m. The rate of perceived exertion, physiological response through the peak and recovery heart rate, blood lactate, and thermoregulatory response through tympanic temperature, were controlled. A repeated measures analysis revealed significant differences throughout EIT in examined variables. Cluster analysis grouped according to the average performance in 400 m runs led to distinguish between athletes with a higher and lower sports level. Cluster analysis was also performed according to age, obtaining an older group and a younger group. The one-way analysis of variance between groups revealed no significant differences (p>=0.05) in the response to EIT. The results provide a detailed description of physiological and thermoregulatory responses to EIT in experienced endurance runners. This allows a better understanding of the impact of a common training stimulus on the physiological level inducing greater accuracy in the training prescription. Moreover, despite the differences in athletic performance or age, the acute physiological and thermoregulatory responses in endurance runners were similar, as long as EIT was performed at similar relative intensity. PMID- 26839622 TI - Positional Role Differences in the Aerobic and Anaerobic Power of Elite Basketball Players. AB - The aim of the present study was to compare the aerobic and anaerobic power and capacity of elite male basketball players who played multiple positions. Fifty five healthy players were divided into the following three different subsamples according to their positional role: guards (n = 22), forwards (n = 19) and centers (n = 14). The following three tests were applied to estimate their aerobic and anaerobic power and capacities: the countermovement jump (CMJ), a multistage shuttle run test and the Running-based Anaerobic Sprint Test (RAST). The obtained data were used to calculate the players' aerobic and anaerobic power and capacities. To determine the possible differences between the subjects considering their different positions on the court, one-way analysis of variance (ANOVA) with the Bonferroni post-hoc test for multiple comparisons was used. The results showed that there was a significant difference between the different groups of players in eleven out of sixteen measured variables. Guards and forwards exhibited greater aerobic and relative values of anaerobic power, allowing shorter recovery times and the ability to repeat high intensity, basketball-specific activities. Centers presented greater values of absolute anaerobic power and capacities, permitting greater force production during discrete tasks. Coaches can use these data to create more individualized strength and conditioning programs for different positional roles. PMID- 26839623 TI - Effect of the Game Design, the Goal Type and the Number of Players on Intensity of Play in Small-Sided Soccer Games in Youth Elite Players. AB - The aim of this study was to compare the effects of game design modification, the type of the goal and the number of players on the intensity of play in small sided soccer games (SSGs) in youth elite players. Twenty young soccer players (age 13.7 +/- 0.5 years, body mass 57.4 +/- 7.8 kg, body height 1.67 +/- 7.8 m, maximal heart rate 201.1 +/- 8.2 beats/min) performed three types of SSGs (possession play (PP) vs. regular goals (RG) vs. small goals (SG)) in both four-a side and six-a-side formats. The heart rate responses were recorded and analysed as an indicator of the intensity of play. The four-a-side format obtained higher intensity of play than six-a-side for PP (p<0.05), but not for SG and RG. SG showed higher intensity of play than RG for four-a-side (p<0.001), but not for six-a-side. PP registered higher intensity of play than RG (p<0.05), but not than SG in four-a-side, whereas in six-a-side no differences were found between the three formats. In conclusion, the modification of variables such as the number of players, the game design and the type of the goal influences the intensity of play in small-sided soccer games in youth players. PMID- 26839624 TI - The Effects of in-Season Repeated Sprint Training Compared to Regular Soccer Training. AB - The aim of this study was to compare the effects of repeated sprints (RSA) training and regular soccer training on Yo-Yo IR-1 and RSA performance (6 x 40 m shuttle sprints). Thirteen semi-professional female soccer players and nine amateur male soccer players were randomised into a repeated sprint group (RSG; n = 12) or a regular soccer training group (STG; n = 10). The RSG soccer players executed 3-4 sets of 4-6 repeated sprints (30 m with 180 degrees directional changes) weekly during the last eight weeks of the in-season. In parallel, the STG soccer players performed low- to moderate intensity soccer training in form of technical or tactical skills. The RSG showed 15% improvement in Yo-Yo IR-1 (p = 0.04; ES = 1.83) and their mean RSA times were reduced by 1.5% (p = 0.02; ES = 0.89). No significant changes were found for the STG (Yo-Yo IR-1, p = 0.13; RSA, p = 0.49). Comparing the groups, greater improvements were observed in Yo-Yo IR-1 for the RSG (p = 0.02; ES = 1.15), but not for the RSA (p = 0.23; ES = -0.33). Similar training volumes and intensities (% of HFmax) were observed between the groups (p = 0.22 and p = 0.79). In conclusion, a weekly RSA session integrated into a regular soccer regime improved in-season RSA and Yo-Yo IR-1 performance compared to regular soccer training. PMID- 26839625 TI - Specific Measurement of Tethered Running Kinetics and its Relationship to Repeated Sprint Ability. AB - Repeated sprint ability has been widely studied by researchers, however, analysis of the relationship between most kinetic variables and the effect of fatigue is still an ongoing process. To search for the best biomechanical parameter to evaluate repeated sprint ability, several kinetic variables were measured in a tethered field running test and compared regarding their sensitivity to fatigue and correlation with time trials in a free running condition. Nine male sprint runners (best average times: 100 m = 10.45 +/- 0.07 s; 200 m = 21.36 +/- 0.17 s; 400 m = 47.35 +/- 1.09 s) completed two test sessions on a synthetic track. Each session consisted of six 35 m sprints interspersed by 10 s rest under tethered field running or free running conditions. Force, power, work, an impulse and a rate of force development were all directly measured using the sensors of a new tethered running apparatus, and a one-way ANOVA with Scheffe post-hoc test used to verify differences between sprints (p < 0.05). Pearson product-moment correlation measured the relationship between mechanical variables and free running performance. A total impulse, the rate of force development and maximum force did not show significant differences for most sprints. These three variables presented low to moderate correlations with free running performance (r between 0.01 and -0.35). Maximum and mean power presented the strongest correlations with free running performance (r = -0.71 and -0.76, respectively; p < 0.001), followed by mean force (r = -0.61; p < 0.001) and total work (r = 0.50; p < 0.001). It was concluded that under a severe work-to-rest ratio condition, power variables were better suited to evaluating repeated sprint ability than the other studied variables. PMID- 26839626 TI - Isokinetic Strength Profile of Elite Female Handball Players. AB - Systematic assessment of muscle strength of the lower extremities throughout the annual training cycle in athletes is crucial from a performance perspective for the optimization of the training process, as well as a health perspective with regard to injury prevention. The main aim of the present study was to determine isokinetic muscle strength of the knee flexors and extensors in female handball players at the beginning of a preparatory period and to assess whether there were any differences between players of different performance levels. The performance level was expressed by means of membership of the Women's Junior National Handball Team (JNT, n=8) or the Women's National Handball Team (NT, n=9). The isokinetic peak torque during concentric and eccentric single-joint knee flexion and extension was measured at angular velocities of 60, 180, 240 degrees /s (concentric) and 60 degrees /s (eccentric). The Mann-Whitney test showed no significant differences in the peak torques or ipsilateral ratios between the two groups. The bilateral force deficit (BFD) for concentric extension at 240 degrees /s was significantly higher in the JNT compared with the NT (p=0.04; d=1.02). However, the results of individual evaluation show that the BFD was more frequent in the NT in most measurements. A high BFD was evident in the eccentric mode in both groups highlighting a need for particular strengthening. With regard to low strength ratios a prevention programme should be suggested for both observed groups of professional female handball players to reduce the risk of injury. PMID- 26839627 TI - Selected Cognitive Abilities in Elite Youth Soccer Players. AB - The identification of talent in soccer is critical to various programs. Although many research findings have been presented, there have been only a few attempts to assess their validity. The aim of this study was to determine the relationship between talent and achievement variables in the Vienna Test System. The participants were 91 Czech soccer players, representing four youth soccer teams, who were born in the year 2000. These boys were divided into two groups according to their coaches' assessments using a TALENT questionnaire. A two-factor model (component 1: "kinetic finesse"; component 2: "mental strength") was designed to interpret the responses of the coaches on the questionnaire. The Vienna Test System was used to determine the level of players' cognitive abilities. In total, the subjects performed seven tests in the following order: Raven's Standard Progressive Matrices (SPM), a reaction test (RT), a determination test (DT), a visual pursuit test (LVT), a Corsi Block-Tapping Test (CORSI), a time/movement anticipation test (ZBA), and a peripheral perception test (PP). To analyze the relationship between talent and achievement variables within the Vienna Test System, correlation analyses were performed. The results revealed that the talented group attained significantly better results on only 1 of the 16 variables, which was ZBA2: movement anticipation - deviation of movement median (r = .217, p = .019). A comparison of the two talent components showed that component 1 ("kinetic finesse") was a more significant factor than component 2 ("mental strength"). Although we observed statistically significant correlations, their actual significance remains questionable; thus, further research is required. PMID- 26839628 TI - Debates in allergy medicine: baked milk and egg ingestion accelerates resolution of milk and egg allergy. AB - Cow's milk and hen's egg are ubiquitous in diets around the world and can be important sources of protein in young children. Unfortunately, milk and egg allergies are also some of the most common food allergies in childhood. Less allergenic forms of milk and egg due to heating and interactions with a food matrix, as in baked goods, are tolerated by a majority of milk- and egg-allergic patients. Adding baked milk and egg into the diets of milk- and egg-allergic children can broaden diets, increase nutrition, and improve quality of life. Most important, regular ingestion of baked milk and egg can help children outgrow their allergies to milk and egg. This article will review our current understanding of baked milk and egg tolerance and outline how these baked forms accelerates tolerance to regular milk and egg. PMID- 26839629 TI - Debates in allergy medicine: baked egg and milk do not accelerate tolerance to egg and milk. AB - There is emerging evidence that children with egg and cow's milk allergy who can tolerate these allergens cooked in baked goods are more likely to develop tolerance. As a result a hypothesis has arisen that exposure to egg and milk in baked goods may hasten tolerance development; however, it is unclear whether children who develop tolerance do so because they have ingested low levels of egg or milk in baked products. An alternative explanation for the improved prognosis in those who can tolerate food allergens in the baked form is that tolerance to egg and milk in baked goods is simply an indicator of a phenotype that is less likely to be persistent. We discuss the role that the baked egg or milk allergy phenotype plays on predicting tolerance development and suggest that it is the phenotype of the disease rather than exposure to altered allergens that is the strongest predictor of tolerance development. PMID- 26839630 TI - Prime and boost aerosol exposure via fog machine or shisha smoke followed by cinnamon hypersensitivity and anaphylaxis to spiced food. AB - BACKGROUND: Cinnamon aldehyde (alias cinnamaldehyde) is widely used in food, textile or cosmetic industry. It is mostly associated with contact allergy, but immediate type allergies have been reported. The present study was triggered by a case of anaphylactic events to cinnamon in food and upon skin prick test. We investigated a possible correlation of exposure to a disco fog machine and/or shisha consumption with immediate type hypersensitivity to cinnamon aldehyde in the patient and healthy volunteers. METHODS & RESULTS: In both fog machines and shisha pipes heating of glycerol-based fluids before evaporation renders chemical transversion to malodorous acrolein. Therefore, both methods are frequently operated with aroma additives. Cinnamon aldehyde and derivatives could be detected by gas chromatography in sampled fog flavored with cola fragrance. The patient as well as healthy (mostly female) volunteers were skin prick tested using cinnamon aldehyde diluted in 0.9 % NaCl, Vaseline(r) or fog fluid. Persons with a history of exposure to disco fog or shisha (n = 10, mean 32.8 years) reacted with a significantly larger wheal and flare reaction in the skin test (p = 0.0115, p = 0.0146, or p = 0.098) than the non-exposed (n = 8, mean 37.3 years). Both groups were gender matched, but differed in the mean age by 4.5 years. This reaction was specific as compared to skin reactivity to cinnamon alcohol, with only a trend to higher reactivity in exposed persons (ns). CONCLUSION: From our data we conclude that hapten fragrances such as cinnamon aldehyde may during heating in glycerol fluids associate to complete antigens and via inspiration lead to specific immediate type hypersensitivity. In some cases the hypersensitivity may be unmasked by spiced food containing cinnamon aldehyde or related chemicals, and lead to severe adverse reactions. PMID- 26839631 TI - Exercise-Induced Changes in Caveolin-1, Depletion of Mitochondrial Cholesterol, and the Inhibition of Mitochondrial Swelling in Rat Skeletal Muscle but Not in the Liver. AB - The reduction in cholesterol in mitochondria, observed after exercise, is related to the inhibition of mitochondrial swelling. Caveolin-1 (Cav-1) plays an essential role in the regulation of cellular cholesterol metabolism and is required by various signalling pathways. Therefore, the aim of this study was to investigate the effect of prolonged swimming on the mitochondrial Cav-1 concentration; additionally, we identified the results of these changes as they relate to the induction of changes in the mitochondrial swelling and cholesterol in rat skeletal muscle and liver. Male Wistar rats were divided into a sedentary control group and an exercise group. The exercised rats swam for 3 hours and were burdened with an additional 3% of their body weight. After the cessation of exercise, their quadriceps femoris muscles and livers were immediately removed for experimentation. The exercise protocol caused an increase in the Cav-1 concentration in crude muscle mitochondria; this was related to a reduction in the cholesterol level and an inhibition of mitochondrial swelling. There were no changes in rat livers, with the exception of increased markers of oxidative stress in mitochondria. These data indicate the possible role of Cav-1 in the adaptive change in the rat muscle mitochondria following exercise. PMID- 26839632 TI - The Coadministration of N-Acetylcysteine Ameliorates the Effects of Arsenic Trioxide on the Male Mouse Genital System. AB - Arsenic trioxide (As2O3) has shown effectiveness in treatment of leukemia but is also associated with reproductive toxicity. Since remediation with N acetylcysteine (NAC) may mitigate the adverse effects caused by exposure, we assessed the effects of As2O3 and its potential reversibility after exposure cessation or coadministration of NAC. Animals received 0.3 or 3.0 mg/Kg/day of As2O3 subcutaneously and 40 mM of NAC in tap water. As2O3 treatment impaired spermatogenesis and sperm motility and decreased seminal vesicle weight and testosterone serum levels; after suspension of treatment, these parameters remained altered. When NAC was administered, animals showed improvement in sperm parameters and seminal vesicle weight. In vitro epididymal contractility was increased in As2O3-treated animals. We concluded that As2O3 is toxic to the male mouse genital system by compromising sperm quality and quantity; these effects persisted even after suspension of the treatment. However, the coadministration of NAC ameliorates the harmful effects of the drug on the male genital system. PMID- 26839633 TI - Targeting TRPM2 Channels Impairs Radiation-Induced Cell Cycle Arrest and Fosters Cell Death of T Cell Leukemia Cells in a Bcl-2-Dependent Manner. AB - Messenger RNA data of lymphohematopoietic cancer lines suggest a correlation between expression of the cation channel TRPM2 and the antiapoptotic protein Bcl 2. The latter is overexpressed in various tumor entities and mediates therapy resistance. Here, we analyzed the crosstalk between Bcl-2 and TRPM2 channels in T cell leukemia cells during oxidative stress as conferred by ionizing radiation (IR). To this end, the effects of TRPM2 inhibition or knock-down on plasma membrane currents, Ca(2+) signaling, mitochondrial superoxide anion formation, and cell cycle progression were compared between irradiated (0-10 Gy) Bcl-2 overexpressing and empty vector-transfected Jurkat cells. As a result, IR stimulated a TRPM2-mediated Ca(2+)-entry, which was higher in Bcl-2 overexpressing than in control cells and which contributed to IR-induced G2/M cell cycle arrest. TRPM2 inhibition induced a release from G2/M arrest resulting in cell death. Collectively, this data suggests a pivotal function of TRPM2 in the DNA damage response of T cell leukemia cells. Apoptosis-resistant Bcl-2 overexpressing cells even can afford higher TRPM2 activity without risking a hazardous Ca(2+)-overload-induced mitochondrial superoxide anion formation. PMID- 26839634 TI - Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice. AB - This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ) induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) delta-aminolevulinate dehydratase (delta-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and delta-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential. PMID- 26839635 TI - Endogenous Sulfur Dioxide: A New Member of Gasotransmitter Family in the Cardiovascular System. AB - Sulfur dioxide (SO2) was previously regarded as a toxic gas in atmospheric pollutants. But it has been found to be endogenously generated from metabolism of sulfur-containing amino acids in mammals through transamination by aspartate aminotransferase (AAT). SO2 could be produced in cardiovascular tissues catalyzed by its synthase AAT. In recent years, studies revealed that SO2 had physiological effects on the cardiovascular system, including vasorelaxation and cardiac function regulation. In addition, the pathophysiological effects of SO2 were also determined. For example, SO2 ameliorated systemic hypertension and pulmonary hypertension, prevented the development of atherosclerosis, and protected against myocardial ischemia-reperfusion (I/R) injury and isoproterenol-induced myocardial injury. These findings suggested that endogenous SO2 was a novel gasotransmitter in the cardiovascular system and provided a new therapy target for cardiovascular diseases. PMID- 26839637 TI - Targeting head and neck tumoral stem cells: From biological aspects to therapeutic perspectives. AB - Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Effective therapeutic modalities such as surgery, radiation, chemotherapy and combinations of each are used in the management of the disease. In most cases, treatment fails to obtain total cancer cure. In recent years, it appears that one of the key determinants of treatment failure may be the presence of cancer stem cells (CSCs) that escape currently available therapies. CSCs form a small portion of the total tumor burden but may play a disproportionately important role in determining outcomes. CSCs have stem features such as self renewal, high migration capacity, drug resistance, high proliferation abilities. A large body of evidence points to the fact that CSCs are particularly resistant to radiotherapy and chemotherapy. In HNSCC, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis and treatment resistance. In the light of such observations, the present review summarizes biological characteristics of CSCs in HNSCC, outlines targeted strategies for the successful eradication of CSCs in HNSCC including targeting the self-renewal controlling pathways, blocking epithelial mesenchymal transition, niche targeting, immunotherapy approaches and highlights the need to better understand CSCs biology for new treatments modalities. PMID- 26839636 TI - Use of bone morphogenetic proteins in mesenchymal stem cell stimulation of cartilage and bone repair. AB - The extracellular matrix-associated bone morphogenetic proteins (BMPs) govern a plethora of biological processes. The BMPs are members of the transforming growth factor-beta protein superfamily, and they actively participate to kidney development, digit and limb formation, angiogenesis, tissue fibrosis and tumor development. Since their discovery, they have attracted attention for their fascinating perspectives in the regenerative medicine and tissue engineering fields. BMPs have been employed in many preclinical and clinical studies exploring their chondrogenic or osteoinductive potential in several animal model defects and in human diseases. During years of research in particular two BMPs, BMP2 and BMP7 have gained the podium for their use in the treatment of various cartilage and bone defects. In particular they have been recently approved for employment in non-union fractures as adjunct therapies. On the other hand, thanks to their potentialities in biomedical applications, there is a growing interest in studying the biology of mesenchymal stem cell (MSC), the rules underneath their differentiation abilities, and to test their true abilities in tissue engineering. In fact, the specific differentiation of MSCs into targeted cell type lineages for transplantation is a primary goal of the regenerative medicine. This review provides an overview on the current knowledge of BMP roles and signaling in MSC biology and differentiation capacities. In particular the article focuses on the potential clinical use of BMPs and MSCs concomitantly, in cartilage and bone tissue repair. PMID- 26839638 TI - Advances in hepatitis C therapy: What is the current state - what come's next? AB - Chronic hepatitis C virus (HCV) infection affects 80-160 million people worldwide and is one of the leading causes of chronic liver disease. It is only a few years ago that standard treatment regimes were based on pegylated interferon alpha and ribavirin. However, treatment of HCV has undergone a revolutionary change in recent years. The admission of the nucleotide polymerase inhibitor Sofosbuvir enabled an interferon-free regimen with direct antiviral agents (DAA). Meanwhile seven DAAs are available and can be applied in several combinations for 8 to 24 wk depending on HCV genotype and patient characteristics such as cirrhosis and chronic renal failure. High rates of sustained virological response (SVR) rates can be achieved with these novel drugs. Even in difficult to treat populations such as patients with liver cirrhosis, HCV-human immunodeficiency virus co infections, after liver transplantion, or with chronic kidney disease comparable high rates of SVR can be achieved. The anticipated 2(nd) generation DAAs are strikingly effective in patients so far classified as difficult to treat including decompensated liver cirrhosis or post-transplant patients. These 2(nd) generations DAAs will have higher resistance barriers, higher antiviral effects and a pan-genotypic spectrum. This review highlights the current state of the art of antiviral treatment in hepatitis C and gives an outlook for upcoming therapies. PMID- 26839640 TI - Innate immunity and hepatocarcinoma: Can toll-like receptors open the door to oncogenesis? AB - Hepatocarcinoma (HCC) is a highly prevalent cancer worldwide and its inflammatory background was established long ago. Recent studies have shown that innate immunity is closely related to the HCC carcinogenesis. An effective innate immunity response relies on the toll-like receptors (TLR) found in several different liver cells which, through different ligands and many signaling pathways can elicit, not only a pro-inflammatory but also an oncogenic or anti oncogenic response. Our aim was to study the role of TLRs in the liver oncogenesis and as a consequence their value as potential therapeutic targets. We performed a systematic review of PubMed searching for original articles studying the relationship between HCC and TLRs until March 2015. TLR2 appears to be a fundamental stress-sensor as its absence reveals an augmented tendency to accumulate DNA-damages and to cell survival. However, pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced tumorigenesis. TLR3 has a well-known protective role influencing crucial processes like angiogenesis, cell growth or proliferation. TLR4 works as an interesting epithelial-mesenchymal transition's inducer and a promoter of cell survival probably inducing HCC carcinogenesis even though an anti-cancer role has already been observed. TLR9's influence on carcinogenesis is also controversial and despite a potential anti-cancer capacity, a pro-tumorigenic role is more likely. Genetic polymorphisms in some TLRs have been found and its influence on the risk of HCC has been reported. As therapeutic targets, TLRs are already in use and have a great potential. In conclusion, TLRs have been shown to be an interesting influence on the HCC's microenvironment, with TLR3 clearly determining an anti-tumour influence. TLR4 and TLR9 are considered to have a positive relationship with tumour development even though, in each of them anti tumorigenic signals have been described. TLR2 presents a more ambiguous role, possibly depending on the stage of the inflammation-HCC axis. PMID- 26839641 TI - Sofosbuvir treatment and hepatitis C virus infection. AB - Hepatitis C virus (HCV) infection is a serious problem worldwide. The use of interferon-based therapy has made HCV eradication challenging. The recent appearance of direct-acting antiviral agents (DAAs) has changed HCV therapy. Combining the use of DAAs with peginterferon and ribavirin has improved treatment efficacy. Furthermore, the combination of different orally administered DAAs has enabled interferon-free therapy with much higher efficacy and safety. In particular, sofosbuvir, a nucleotide-based NS5B inhibitor, prevents HCV RNA synthesis by acting as a "chain terminator". Treatment with sofosbuvir has attained an extremely high rate of sustained virologic response. The current review summarizes the efficacy and safety of sofosbuvir therapy. PMID- 26839639 TI - Management of immunosuppressant agents following liver transplantation: Less is more. AB - Immunosuppression in organ transplantation was revolutionary for its time, but technological and population changes cast new light on its use. First, metabolic syndrome (MS) is increasing as a public health issue, concomitantly increasing as an issue for post-orthotopic liver transplantation patients; yet the medications regularly used for immunosuppression contribute to dysfunctional metabolism. Current mainstay immunosuppression involves the use of calcineurin inhibitors; these are potent, but nonspecifically disrupt intracellular signaling in such a way as to exacerbate the impact of MS on the liver. Second, the impacts of acute cellular rejection and malignancy are reviewed in terms of their severity and possible interactions with immunosuppressive medications. Finally, immunosuppressive agents must be considered in terms of new developments in hepatitis C virus treatment, which undercut what used to be inevitable viral recurrence. Overall, while traditional immunosuppressive agents remain the most used, the specific side-effect profiles of all immunosuppressants must be weighed in light of the individual patient. PMID- 26839642 TI - Ablation techniques for primary and metastatic liver tumors. AB - Ablative treatment methods have emerged as safe and effective therapies for patients with primary and secondary liver tumors who are not surgical candidates at the time of diagnosis. This article reviews the current literature and describes the techniques, complications and results for radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation. PMID- 26839643 TI - Cirrhotic cardiomyopathy: Isn't stress evaluation always required for the diagnosis? AB - AIM: To describe the proportion of patients with cirrhotic cardiomyopathy (CCM) evaluated by stress echocardiography and investigating its association with the severity of liver disease. METHODS: A cross-sectional study was conducted. Cirrhotic patients without risk factors for cardiovascular disease were included. Data regarding etiology and severity of liver disease (Child-Pugh score and model for end-stage liver disease), presence of ascites and gastroesophageal varices, pro-brain natriuretic peptide (pro-BNP) and corrected QT (QTc) interval were collected. Dobutamine stress echocardiography (conventional and tissue Doppler imaging) was performed. CCM was considered present when diastolic and/or systolic dysfunction was diagnosed at rest or after pharmacological stress. Therapy interfering with cardiovascular system was suspended 24 h before the examination. RESULTS: Twenty-six patients were analyzed, 17 (65.4%) Child-Pugh A, mean model for end-stage liver disease (MELD) score of 8.7. The global proportion of patients with CCM was 61.5%. At rest, only 2 (7.7%) patients had diastolic dysfunction and none of the patients had systolic dysfunction. Dobutamine stress echocardiography revealed the presence of diastolic dysfunction in more 6 (23.1%) patients and of systolic dysfunction in 10 (38.5%) patients. QTc interval prolongation was observed in 68.8% of the patients and increased pro-BNP levels in 31.2% of them. There was no association between the presence of CCM and liver impairment assessed by Child-Pugh score or MELD (P = 0.775, P = 0.532, respectively). Patients with QTc interval prolongation had a significant higher rate of gastroesophageal varices comparing with those without QTc interval prolongation (95.0% vs 50.0%, P = 0.028). CONCLUSION: CCM is a frequent complication of cirrhosis that is independent of liver impairment. Stress evaluation should always be performed, otherwise it will remain an underdiagnosed condition. PMID- 26839644 TI - Endoscopic treatment of esophageal achalasia. AB - Achalasia is a motility disorder of the esophagus characterized by dysphagia, regurgitation of undigested food, chest pain, weight loss and respiratory symptoms. The most common form of achalasia is the idiopathic one. Diagnosis largely relies upon endoscopy, barium swallow study, and high resolution esophageal manometry (HRM). Barium swallow and manometry after treatment are also good predictors of success of treatment as it is the residue symptomatology. Short term improvement in the symptomatology of achalasia can be achieved with medical therapy with calcium channel blockers or endoscopic botulin toxin injection. Even though few patients can be cured with only one treatment and repeat procedure might be needed, long term relief from dysphagia can be obtained in about 90% of cases with either surgical interventions such as laparoscopic Heller myotomy or with endoscopic techniques such pneumatic dilatation or, more recently, with per-oral endoscopic myotomy. Age, sex, and manometric type by HRM are also predictors of responsiveness to treatment. Older patients, females and type II achalasia are better after treatment compared to younger patients, males and type III achalasia. Self-expandable metallic stents are an alternative in patients non responding to conventional therapies. PMID- 26839646 TI - Laparoscopic esophagomyotomy for achalasia in children: A review. AB - Esophageal achalasia in children is rare but ultimately requires endoscopic or surgical treatment. Historically, Heller esophagomyotomy has been recommended as the treatment of choice. The refinement of minimally invasive techniques has shifted the trend of treatment toward laparoscopic Heller myotomy (LHM) in adults and children with achalasia. A review of the available literature on LHM performed in patients < 18 years of age was conducted. The pediatric LHM experience is limited to one multi-institutional and several single-institutional retrospective studies. Available data suggest that LHM is safe and effective. There is a paucity of evidence on the need for and superiority of concurrent antireflux procedures. In addition, a more complete portrayal of complications and long-term (> 5 years) outcomes is needed. Due to the infrequency of achalasia in children, these characteristics are unlikely to be defined without collaboration between multiple pediatric surgery centers. The introduction of peroral endoscopic myotomy and single-incision techniques, continue the trend of innovative approaches that may eventually become the standard of care. PMID- 26839645 TI - Colorectal endoscopic submucosal dissection from a Western perspective: Today's promises and future challenges. AB - Over the last few years, endoscopic submucosal dissection (ESD) has shown to be effective in the management of early colorectal neoplasms, particularly in Asian countries where the technique was born. In the Western world, its implementation has been slow and laborious. In this paper, the indications for ESD, its learning model, the available methods to predict the presence of deep submucosal invasion before the procedure and the published outcomes from Asia and Europe will be reviewed. Since ESD has several limitations in terms of learning achievement in the West, and completion of the procedure for the first cases is difficult in our part of the world, a short review on colorectal assisted ESD has been included. Finally, other endoscopic and surgical treatment modalities that are in competition with colorectal ESD will be summarized. PMID- 26839647 TI - Endoscopic ultrasound in the diagnosis and management of carcinoma pancreas. AB - Endoscopic ultrasound (EUS) has become an important component in the diagnosis and treatment of carcinoma pancreas. With the advent of advanced imaging techniques and tissue acquisition methods the role of EUS is becoming increasingly important. Small pancreatic tumors can be reliably diagnosed with EUS. EUS guided fine needle aspiration establishes diagnosis in some cases. EUS plays an important role in staging of carcinoma pancreas and in some important therapeutic methods that include celiac plexus neurolysis, EUS guided biliary drainage and drug delivery. In this review we attempt to review the role of EUS in diagnosis and management of carcinoma pancreas. PMID- 26839648 TI - Drug eluting biliary stents to decrease stent failure rates: A review of the literature. AB - Biliary stenting is clinically effective in relieving both malignant and non malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy. PMID- 26839649 TI - Submucosal tunnel endoscopy: Peroral endoscopic myotomy and peroral endoscopic tumor resection. AB - Peroral endoscopic myotomy (POEM) is an innovative, minimally invasive, endoscopic treatment for esophageal achalasia and other esophageal motility disorders, emerged from the natural orifice transluminal endoscopic surgery procedures, and since the first human case performed by Inoue in 2008, showed exciting results in international level, with more than 4000 cases globally up to now. POEM showed superior characteristics than the standard 100-year-old surgical or laparoscopic Heller myotomy (LHM), not only for all types of esophageal achalasia [classical (I), vigorous (II), spastic (III), Chicago Classification], but also for advanced sigmoid type achalasia (S1 and S2), failed LHM, or other esophageal motility disorders (diffuse esophageal spasm, nutcracker esophagus or Jackhammer esophagus). POEM starts with a mucosal incision, followed by submucosal tunnel creation crossing the esophagogastric junction (EGJ) and myotomy. Finally the mucosal entry is closed with endoscopic clip placement. POEM permitted relatively free choice of myotomy length and localization. Although it is technically demanding procedure, POEM can be performed safely and achieves very good control of dysphagia and chest pain. Gastroesophageal reflux is the most common troublesome side effect, and is well controllable with proton pump inhibitors. Furthermore, POEM opened the era of submucosal tunnel endoscopy, with many other applications. Based on the same principles with POEM, in combination with new technological developments, such as endoscopic suturing, peroral endoscopic tumor resection (POET), is safely and effectively applied for challenging submucosal esophageal, EGJ and gastric cardia tumors (submucosal tumors), emerged from muscularis propria. POET showed up to know promising results, however, it is restricted to specialized centers. The present article reviews the recent data of POEM and POET and discussed controversial issues that need further study and future perspectives. PMID- 26839651 TI - Evidence to suggest adoption of water exchange deserves broader consideration: Its pain alleviating impact occurs in 90% of investigators. AB - AIM: To determine whether observations were reproducible among investigators. METHODS: From March 2013 through June 2014, 18-85-year-old diagnostic and 50-70 year-old screening patients were enrolled at each center to on-demand sedation colonoscopy with water exchange (WE), water immersion (WI) and insufflation with air or CO2 for insertion and withdrawal [air or carbon dioxide (AICD)]. Data were aggregated for analysis. PRIMARY OUTCOME: Variations in real-time maximum insertion pain (0 = none, 1-2 = discomfort, 10 = worst). RESULTS: One thousand and ninety-one cases analyzed: WE (n = 371); WI (n = 338); AICD (n = 382). Demographics and indications were comparable. The WE group had the lowest real time maximum insertion pain score, mean (95%CI): WE 2.8 (2.6-3.0), WI 3.8 (3.5 4.1) and AICD 4.4 (4.1-4.7), P < 0.0005. Ninety percent of the colonoscopists were able to use water exchange to significantly decrease maximum insertion pain scores. One investigator had high insertion pain in all groups, nonetheless WE achieved the lowest real-time maximum insertion pain score. WE had the highest proportions of patients with painless unsedated colonoscopy (vs WI, P = 0.013; vs AICD, P < 0.0005); unsedated colonoscopy with only minor discomfort (vs AICD, P < 0.0005), and completion without sedation (vs AICD, P < 0.0005). CONCLUSION: Aggregate data confirm superiority of WE in lowering colonoscopy real-time maximum insertion pain and need for sedation. Ninety percent of investigators were able to use water exchange to significantly decrease maximum insertion pain scores. Our results suggest that the technique deserves consideration in a broader scale. PMID- 26839650 TI - Endoscopic ultrasound-guided interventions in special situations. AB - Endoscopic ultrasound (EUS) was introduced in 1982 and has since become a popular advanced procedure for diagnosis and therapeutic intervention. Initially, EUS was most commonly used for the diagnosis of pancreatobiliary diseases and tissue acquisition. EUS was first used for guided cholangiography in 1996, followed by EUS-guided biliary drainage in 2001. Advancements in equipment and endoscopic accessories have led to an expansion of EUS-guided procedures, which now include EUS-guided drainage of intra-abdominal abscesses or collections, intra-vascular treatment of refractory variceal and nonvariceal bleeding, transmural pancreatic drainage, common bile duct stone clearance, enteral feeding tube placement and entero-enteric anastomosis. Patients with surgically altered upper gastrointestinal anatomies have greatly benefited from EUS also. This systematic review describes and discusses EUS procedures performed in uncommon diseases and conditions, as well as applications on more vulnerable patients such as young children and pregnant women. In these cases, routine approaches do not always apply, and thus may require the use of innovative and unconventional techniques. Increased knowledge of such special applications will help increase the success rates of these procedures and provide a foundation for additional advances and utilizations of the technique. PMID- 26839652 TI - Brain changes in diabetes mellitus patients with gastrointestinal symptoms. AB - Diabetes mellitus is a common disease and its prevalence is increasing worldwide. In various studies up to 30%-70% of patients present dysfunction and complications related to the gut. To date several clinical studies have demonstrated that autonomic nervous system neuropathy and generalized neuropathy of the central nervous system (CNS) may play a major role. This systematic review provides an overview of the neurodegenerative changes that occur as a consequence of diabetes with a focus on the CNS changes and gastrointestinal (GI) dysfunction. Animal models where diabetes was induced experimentally support that the disease induces changes in CNS. Recent investigations with electroencephalography and functional brain imaging in patients with diabetes confirm these structural and functional brain changes. Encephalographic studies demonstrated that altered insular processing of sensory stimuli seems to be a key player in symptom generation. In fact one study indicated that the more GI symptoms the patients experienced, the deeper the insular electrical source was located. The electroencephalography was often used in combination with quantitative sensory testing mainly showing hyposensitivity to stimulation of GI organs. Imaging studies on patients with diabetes and GI symptoms mainly showed microstructural changes, especially in brain areas involved in visceral sensory processing. As the electrophysiological and imaging changes were associated with GI and autonomic symptoms they may represent a future therapeutic target for treating diabetics either pharmacologically or with neuromodulation. PMID- 26839653 TI - From bariatric to metabolic surgery: Looking for a "disease modifier" surgery for type 2 diabetes. AB - In this review the recent evolution of the comprehension of clinical and metabolic consequences of bariatric surgery is depicted. At the beginning bariatric surgery aim was a significant and durable weight loss. Later on, it became evident that bariatric surgery was associated with metabolic changes, activated by unknown pathways, partially or totally independent of weight loss. Paradigm of this "metabolic" surgery is its effects on type 2 diabetes mellitus (T2DM). In morbid obese subjects it was observed a dramatic metabolic response leading to decrease blood glucose, till diabetes remission, before the achievement of clinically significant weight loss, opening the avenue to search for putative anti-diabetic "intestinal" factors. Both proximal duodenal (still unknown) and distal (GLP1) signals have been suggested as hormonal effectors of surgery on blood glucose decrease. Despite these findings T2DM remission was never considered a primary indication for bariatric surgery but only a secondary one. Recently T2DM remission in obese subjects with body mass index (BMI) greater than 35 has become a primary aim for surgery. This change supports the idea that "metabolic surgery" definition could more appropriate than bariatric, allowing to explore the possibility that metabolic surgery could represent a "disease modifier" for T2DM. Therefore, several patients have undergone surgery with a primary aim of a definitive cure of T2DM and today this surgery can be proposed as an alternative therapy. How much surgery can be considered truly metabolic is still unknown. To be truly "metabolic" it should be demonstrated that surgery could cause T2DM remission not only in subjects with BMI > 35 but also with BMI < 35 or even < 30. Available evidence on this topic is discussed in this mini review. PMID- 26839655 TI - Population-level differences in revascularization treatment and outcomes among various United States subpopulations. AB - Despite recent general improvements in health care, significant disparities persist in the cardiovascular care of women and racial/ethnic minorities. This is true even when income, education level, and site of care are taken into consideration. Possible explanations for these disparities include socioeconomic considerations, elements of discrimination and racism that affect socioeconomic status, and access to adequate medical care. Coronary revascularization has become the accepted and recommended treatment for myocardial infarction (MI) today and is one of the most common major medical interventions in the United States, with more than 1 million procedures each year. This review discusses recent data on disparities in co-morbidities and presentation symptoms, care and access to medical resources, and outcomes in revascularization as treatment for acute coronary syndrome, looking especially at women and minority populations in the United States. The data show that revascularization is used less in both female and minority patients. We summarize recent data on disparities in co morbidities and presentation symptoms related to MI; access to care, medical resources, and treatments; and outcomes in women, blacks, and Hispanics. The picture is complicated among the last group by the many Hispanic/Latino subgroups in the United States. Some differences in outcomes are partially explained by presentation symptoms and co-morbidities and external conditions such as local hospital capacity. Of particular note is the striking differential in both presentation co-morbidities and mortality rates seen in women, compared to men, especially in women <= 55 years of age. Surveillance data on other groups in the United States such as American Indians/Alaska Natives and the many Asian subpopulations show disparities in risk factors and co-morbidities, but revascularization as treatment for MI in these populations has not been adequately studied. Significant research is required to understand the extent of disparities in treatment in these subpopulations. PMID- 26839656 TI - Surgical perspectives in the management of atrial fibrillation. AB - Atrial fibrillation (AF) is the most common cardiac arrhythmia and a huge public health burden associated with significant morbidity and mortality. For decades an increasing number of patients have undergone surgical treatment of AF, mainly during concomitant cardiac surgery. This has sparked a drive for conducting further studies and researching this field. With the cornerstone Cox-Maze III "cut and sew" procedure being technically challenging, the focus in current literature has turned towards less invasive techniques. The introduction of ablative devices has revolutionised the surgical management of AF, moving away from the traditional surgical lesions. The hybrid procedure, a combination of catheter and surgical ablation is another promising new technique aiming to improve outcomes. Despite the increasing number of studies looking at various aspects of the surgical management of AF, the literature would benefit from more uniformly conducted randomised control trials. PMID- 26839658 TI - Cardiovascular drugs in the treatment of infantile hemangioma. AB - Since the introduction of propranolol in the treatment of complicated infantile hemangiomas (IH) in 2008, other different beta-blockers, including timolol, acetabutolol, nadolol and atenolol, have been successfully used for the same purpose. Various hypotheses including vasoconstriction, inhibition of angiogenesis and the induction of apoptosis in proliferating endothelial cells have been advanced as the potential beta-blocker-induced effect on the accelerated IH involution, although the exact mechanism of action of beta blockers remains unknown. This has generated an extraordinary interest in IH research and has led to the discovery of the role of the renin-angiotensin system (RAS) in the biology of IH, providing a plausible explanation for the beta blocker induced effect on IH involution and the development of new potential indications for RAS drugs such as angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers in the treatment of IH. This review is focused on the current use of cardiovascular drugs in the treatment of IH. PMID- 26839654 TI - Genetics of coronary artery disease and myocardial infarction. AB - Atherosclerotic coronary artery disease (CAD) comprises a broad spectrum of clinical entities that include asymptomatic subclinical atherosclerosis and its clinical complications, such as angina pectoris, myocardial infarction (MI) and sudden cardiac death. CAD continues to be the leading cause of death in industrialized society. The long-recognized familial clustering of CAD suggests that genetics plays a central role in its development, with the heritability of CAD and MI estimated at approximately 50% to 60%. Understanding the genetic architecture of CAD and MI has proven to be difficult and costly due to the heterogeneity of clinical CAD and the underlying multi-decade complex pathophysiological processes that involve both genetic and environmental interactions. This review describes the clinical heterogeneity of CAD and MI to clarify the disease spectrum in genetic studies, provides a brief overview of the historical understanding and estimation of the heritability of CAD and MI, recounts major gene discoveries of potential causal mutations in familial CAD and MI, summarizes CAD and MI-associated genetic variants identified using candidate gene approaches and genome-wide association studies (GWAS), and summarizes the current status of the construction and validations of genetic risk scores for lifetime risk prediction and guidance for preventive strategies. Potential protective genetic factors against the development of CAD and MI are also discussed. Finally, GWAS have identified multiple genetic factors associated with an increased risk of in-stent restenosis following stent placement for obstructive CAD. This review will also address genetic factors associated with in stent restenosis, which may ultimately guide clinical decision-making regarding revascularization strategies for patients with CAD and MI. PMID- 26839659 TI - Pulmonary vein stenosis: Etiology, diagnosis and management. AB - Pulmonary vein stenosis (PVS) is rare condition characterized by a challenging diagnosis and unfavorable prognosis at advance stages. At present, injury from radiofrequency ablation for atrial fibrillation has become the main cause of the disease. PVS is characterized by a progressive lumen size reduction of one or more pulmonary veins that, when hemodynamically significant, may raise lobar capillary pressure leading to signs and symptoms such as shortness of breath, cough, and hemoptysis. Image techniques (transesophageal echocardiography, computed tomography, magnetic resonance and perfusion imaging) are essential to reach a final diagnosis and decide an appropriate therapy. In this regard, series from referral centers have shown that surgical and transcatheter interventions may improve prognosis. The purpose of this article is to review the etiology, assessment and management of PVS. PMID- 26839660 TI - Bicuspid aortic valve hemodynamics does not promote remodeling in porcine aortic wall concavity. AB - AIM: To investigate the role of type-I left-right bicuspid aortic valve (LR-BAV) hemodynamic stresses in the remodeling of the thoracic ascending aorta (AA) concavity, in the absence of underlying genetic or structural defects. METHODS: Transient wall shear stress (WSS) profiles in the concavity of tricuspid aortic valve (TAV) and LR-BAV AAs were obtained computationally. Tissue specimens excised from the concavity of normal (non-dilated) porcine AAs were subjected for 48 h to those stress environments using a shear stress bioreactor. Tissue remodeling was characterized in terms of matrix metalloproteinase (MMP) expression and activity via immunostaining and gelatin zymography. RESULTS: Immunostaining semi-quantification results indicated no significant difference in MMP-2 and MMP-9 expression between the tissue groups exposed to TAV and LR-BAV AA WSS (P = 0.80 and P = 0.19, respectively). Zymography densitometry revealed no difference in MMP-2 activity (total activity, active form and latent form) between the groups subjected to TAV AA and LR-BAV AA WSS (P = 0.08, P = 0.15 and P = 0.59, respectively). CONCLUSION: The hemodynamic stress environment present in the concavity of type-I LR-BAV AA does not cause any significant change in proteolytic enzyme expression and activity as compared to that present in the TAV AA. PMID- 26839661 TI - Percutaneous assist devices in acute myocardial infarction with cardiogenic shock: Review, meta-analysis. AB - AIM: To assess the impact of percutaneous cardiac support in cardiogenic shock (CS) complicating acute myocardial infarction (AMI), treated with percutaneous coronary intervention. METHODS: We selected all of the studies published from January 1(st), 1997 to May 15(st), 2015 that compared the following percutaneous mechanical support in patients with CS due to AMI undergoing myocardial revascularization: (1) intra-aortic balloon pump (IABP) vs Medical therapy; (2) percutaneous left ventricular assist devices (PLVADs) vs IABP; (3) complete extracorporeal life support with extracorporeal membrane oxygenation (ECMO) plus IABP vs IABP alone; and (4) ECMO plus IABP vs ECMO alone, in patients with AMI and CS undergoing myocardial revascularization. We evaluated the impact of the support devices on primary and secondary endpoints. Primary endpoint was the inhospital mortality due to any cause during the same hospital stay and secondary endpoint late mortality at 6-12 mo of follow-up. RESULTS: One thousand two hundred and seventy-two studies met the initial screening criteria. After detailed review, only 30 were selected. There were 6 eligible randomized controlled trials and 24 eligible observational studies totaling 15799 patients. We found that the inhospital mortality was: (1) significantly higher with IABP support vs medical therapy (RR = +15%, P = 0.0002); (2) was higher, although not significantly, with PLVADs compared to IABP (RR = +14%, P = 0.21); and (3) significantly lower in patients treated with ECMO plus IABP vs IABP (RR = -44%, P = 0.0008) or ECMO (RR = -20%, P = 0.006) alone. In addition, Trial Sequential Analysis showed that in the comparison of IABP vs medical therapy, the sample size was adequate to demonstrate a significant increase in risk due to IABP. CONCLUSION: Inhospital mortality was significantly higher with IABP vs medical therapy. PLVADs did not reduce early mortality. ECMO plus IABP significantly reduced inhospital mortality compared to IABP. PMID- 26839657 TI - Ventricular repolarization measures for arrhythmic risk stratification. AB - Ventricular repolarization is a complex electrical phenomenon which represents a crucial stage in electrical cardiac activity. It is expressed on the surface electrocardiogram by the interval between the start of the QRS complex and the end of the T wave or U wave (QT). Several physiological, pathological and iatrogenic factors can influence ventricular repolarization. It has been demonstrated that small perturbations in this process can be a potential trigger of malignant arrhythmias, therefore the analysis of ventricular repolarization represents an interesting tool to implement risk stratification of arrhythmic events in different clinical settings. The aim of this review is to critically revise the traditional methods of static analysis of ventricular repolarization as well as those for dynamic evaluation, their prognostic significance and the possible application in daily clinical practice. PMID- 26839663 TI - Easier and Safer Regional Anesthesia and Peripheral Nerve Block under Ultrasound Guidance. PMID- 26839662 TI - Electrophysiologic testing guided risk stratification approach for sudden cardiac death beyond the left ventricular ejection fraction. AB - Sudden cardiac death threats ischaemic and dilated cardiomyopathy patients. Anti- arrhythmic protection may be provided to these patients with implanted cardiac defibrillators (ICD), after an efficient risk stratification approach. The proposed risk stratifier of an impaired left ventricular ejection fraction has limited sensitivity meaning that a significant number of victims will remain undetectable by this risk stratification approach because they have a preserved left ventricular systolic function. Current risk stratification strategies focus on combinations of non invasive methods like T wave alternans, late potentials, heart rate turbulence, deceleration capacity and others, with invasive methods like the electrophysiologic study. In the presence of an electrically impaired substrate with formed post myocardial infarction fibrotic zones, programmed ventricular stimulation provides important prognostic information for the selection of the patients expected to benefit from an ICD implantation, while due to its high negative predictive value, patients at low risk level may also be detected. Clustering evidence from different research groups and electrophysiologic labs support an electrophysiologic testing guided risk stratification approach for sudden cardiac death. PMID- 26839664 TI - Neural Ablation and Regeneration in Pain Practice. AB - A nerve block is an effective tool for diagnostic and therapeutic methods. If a diagnostic nerve block is successful for pain relief and the subsequent therapeutic nerve block is effective for only a limited duration, the next step that should be considered is a nerve ablation or modulation. The nerve ablation causes iatrogenic neural degeneration aiming only for sensory or sympathetic denervation without motor deficits. Nerve ablation produces the interruption of axonal continuity, degeneration of nerve fibers distal to the lesion (Wallerian degeneration), and the eventual death of axotomized neurons. The nerve ablation methods currently available for resection/removal of innervation are performed by either chemical or thermal ablation. Meanwhile, the nerve modulation method for interruption of innervation is performed using an electromagnetic field of pulsed radiofrequency. According to Sunderland's classification, it is first and foremost suggested that current neural ablations produce third degree peripheral nerve injury (PNI) to the myelin, axon, and endoneurium without any disruption of the fascicular arrangement, perineurium, and epineurium. The merit of Sunderland's third degree PNI is to produce a reversible injury. However, its shortcoming is the recurrence of pain and the necessity of repeated ablative procedures. The molecular mechanisms related to axonal regeneration after injury include cross-talk between axons and glial cells, neurotrophic factors, extracellular matrix molecules, and their receptors. It is essential to establish a safe, long-standing denervation method without any complications in future practices based on the mechanisms of nerve degeneration as well as following regeneration. PMID- 26839666 TI - Ultrasound Guided Low Approach Interscalene Brachial Plexus Block for Upper Limb Surgery. AB - BACKGROUND: The interscalene brachial plexus block is widely used for pain control and anesthetic purposes during shoulder arthroscopic surgeries and surgeries of the upper extremities. However, it is known that interscalene brachial plexus block is not appropriate for upper limb surgeries because it does not affect the lower trunk (C8-T1, ulnar nerve) of the brachial plexus. METHODS: A low approach, ultrasound-guided interscalene brachial plexus block (LISB) was performed on twenty-eight patients undergoing surgery of the upper extremities. The patients were assessed five minutes and fifteen minutes after the block for the degree of block in each nerve and muscle as well as for any complications. RESULTS: At five minutes and fifteen minutes after the performance of the block, the degree of the block in the ulnar nerve was found to be 2.8 +/- 2.6 and 1.1 +/ 1.8, respectively, based on a ten-point scale. Motor block occurred in the median nerve after fifteen minutes in 26 of the 28 patients (92.8%), and in all of the other three nerves in all 28 patients. None of the patients received additional analgesics, and none experienced complications. CONCLUSIONS: The present study confirmed the achievement of an appropriate sensory and motor block in the upper extremities, including the ulnar nerve, fifteen minutes after LISB, with no complications. PMID- 26839665 TI - Evaluation of Efficacy of Ultrasonography in the Assessment of Transcutaneous Electrical Nerve Stimulation in Subjects with Myositis and Myofascial Pain. AB - BACKGROUND: The study aimed to determine if ultrasonography of masseter can be used to evaluate the outcome of transcutaneous electrical nerve stimulation (TENS) in subjects with temporomandibular disorders (TMDs) such as myositis and myofascial pain. METHODS: Fifteen TMD subjects with myofascial pain/myositis who satisfied the RDC/McNeil criteria were included in the study. All the subjects were administered TENS therapy for a period of 6 days (30 minutes per session). The mouth opening (in millimeters) and severity of pain (visual analogue scale score) and ultrasonographic thickness of the masseter (in millimeters) in the region of trigger/tender areas was assessed in all the subjects both prior and post TENS therapy. A comparison of the pre-treatment and post-treatment values of the VAS score, mouth opening and masseter thickness was done with the help of a t test. RESULTS: There was a significant reduction in the thickness of masseter muscle (P = 0.028) and VAS scores (P < 0.001) post TENS therapy. There was also a significant improvement in the mouth opening (P = 0.011) post TENS therapy. CONCLUSIONS: In the present study, ultrasonography was found to be an effective measuring tool in the assessment of TENS therapy in subjects with myositis and myofascial pain. PMID- 26839667 TI - Caudal Neuromodulation with the Transforaminal Sacral Electrode (InterStim(r)): Experience in a Pain Center Regarding 12 Implants. AB - BACKGROUND: Sacral nerve stimulation is a therapeutic option with demonstrated efficacy for conditions presenting with perineal pain caused by different etiologies. We aimed to assess whether a sacral electrode (InterStim(r), Medtronic, Minneapolis, MN, USA) inserted through the caudal pathway is able to offer an acceptable level of sacral stimulation and rate of catheter migration. METHODS: We present 12 patients with pelvic pain who received sacral neuromodulation via the sacral hiatus with the InterStim electrode. We evaluated patient satisfaction as well as migration and removal of the electrode, if necessary. RESULTS: Our experience included 12 patients, 10 women and two men, with a mean age of 60 years. In eight of the 12 patients, the initial therapy was effective, and the final system implantation was performed. During subsequent follow-up, patient satisfaction was good. To date, there have been no cases of electrode displacement or migration. CONCLUSIONS: The caudal insertion of the InterStim electrode, with its own fixation system, and initially designed for transsacral insertion, appears in our experience to be a satisfactory option which can minimize electrode displacements, achieving similar results in therapeutic efficacy and causing no difficulties in removal. PMID- 26839668 TI - Dexamethasone or Dexmedetomidine as Local Anesthetic Adjuvants for Ultrasound guided Axillary Brachial Plexus Blocks with Nerve Stimulation. AB - BACKGROUND: The purpose of this study was to evaluate the effect of dexamethasone or dexmedetomidine added to ropivacaine on the onset and duration of ultrasound guided axillary brachial plexus blocks (BPB). METHODS: Fifty-one ASA physical status I-II patients with elective forearm and hand surgery under axillary brachial plexus blocks were randomly allocated to receive 20 ml of 0.5% ropivacaine with 2 ml of isotonic saline (C group, n = 17), 20 ml of 0.5% ropivacaine with 2 ml (10 mg) of dexamethasone (D group, n = 17) or 20 ml of 0.5% ropivacaine with 2 ml (100 ug) of dexmedetomidine (DM group, n = 17). A nerve stimulation technique with ultrasound was used in all patients. The onset time and duration of sensory blocks were assessed. RESULTS: The duration of the sensory block was extended in group D and group DX compared with group C (P < 0.05), but there was no significant difference between group D and group DX. However, there were no significant differences in onset time in all three groups. CONCLUSIONS: Dexamethasone 10 mg and dexmedetomidine 100 ug were equally effective in extending the duration of ropivacaine in ultrasound-guided axillary BPB with nerve stimulation. However, neither drug has significantly effects the onset time. PMID- 26839669 TI - The Influence of Genotype Polymorphism on Morphine Analgesic Effect for Postoperative Pain in Children. AB - BACKGROUND: Although opioids are the most commonly used medications to control postoperative pain in children, the analgesic effects could have a large inter individual variability according to genotypes. The aim of this study was to investigate the association between single nucleotide polymorphisms and the analgesic effect of morphine for postoperative pain in children. METHODS: A prospective study was conducted in 88 healthy children undergoing tonsillectomy, who received morphine during the operation. The postoperative pain score, frequency of rescue analgesics, and side effects of morphine were assessed in the post-anesthesia care unit. The children were genotyped for OPRM1 A118G, ABCB1 C3435T, and COMT Val158Met. RESULTS: Children with at least one G allele for OPRM1 (AG/GG) had higher postoperative pain scores compared with those with the AA genotype at the time of discharge from the post-anesthesia care unit (P = 0.025). Other recovery profiles were not significantly different between the two groups. There was no significant relationship between genotypes and postoperative pain scores in analysis of ABCB1 and COMT polymorphisms. CONCLUSIONS: Genetic polymorphism at OPRM1 A118G, but not at ABCB1 C3435T and COMT Val158Met, influences the analgesic effect of morphine for immediate acute postoperative pain in children. PMID- 26839670 TI - Nefopam Reduces Dysesthesia after Percutaneous Endoscopic Lumbar Discectomy. AB - BACKGROUND: Neuropathic pain, including paresthesia/dysesthesia in the lower extremities, always develops and remains for at least one month, to variable degrees, after percutaneous endoscopic lumbar discectomy (PELD). The recently discovered dual analgesic mechanisms of action, similar to those of antidepressants and anticonvulsants, enable nefopam (NFP) to treat neuropathic pain. This study was performed to determine whether NFP might reduce the neuropathic pain component of postoperative pain. METHODS: Eighty patients, who underwent PELD due to herniated nucleus pulposus (HNP) at L4-L5, were randomly divided into two equal groups, one receiving NFP (with a mixture of morphine and ketorolac) and the other normal saline (NS) with the same mixture. The number of bolus infusions and the infused volume for 3 days were compared in both groups. The adverse reactions (ADRs) in both groups were recorded and compared. The neuropathic pain symptom inventory (NPSI) score was compared in both groups on postoperative days 1, 3, 7, 30, 60, and 90. RESULTS: The mean attempted number of bolus infusions, and effective infused bolus volume for 3 days was lower in the NFP group for 3 days. The most commonly reported ADRs were nausea, dizziness, and somnolence, in order of frequency in the NFP group. The median NPSI score, and all 5 median sub-scores in the NFP group, were significantly lower than that of the NS group until postoperative day 30. CONCLUSIONS: NFP significantly reduced the neuropathic pain component, including paresthesia/dysesthesia until 1 month after PELD. The common ADRs were nausea, dizziness, somnolence, and ataxia. PMID- 26839671 TI - Misconceived Retropharyngeal Calcific Tendinitis during Management of Myofascial Neck Pain Syndrome. AB - Differential diagnosis of posterior neck pain is very challenging based on symptoms and physical examination only. Retropharyngeal calcific tendinitis is a rare and frequently misdiagnosed entity in various causes of neck pain. It results from calcium hydroxyapatite deposition in the longus colli muscle which is characterized by severe neck pain, painful restriction of neck movement, dysphagia, and odynophagia. We herein report a case of a patient with acute retropharyngeal calcific tendinitis, who complained of posterior neck pain, initially diagnosed and treated as a myofascial neck pain syndrome. PMID- 26839672 TI - Pulsed Radiofrequency Application for the Treatment of Pain Secondary to Sacroiliac Joint Metastases. AB - Sacroiliac (SI) joint pain can result from degeneration, infection, malignancy, and trauma. Patients with metastatic bone pain who do not respond to conventional treatment may need more aggressive neuroinvasive approaches. Recently, pulsed radiofrequency (PRF) neuromodulation has emerged as a promising treatment alternative for refractory cases of SI joint pain. Nevertheless, there is no report on the treatment of pain arising from SI joint metastases with PRF. We are reporting about a 63-year-old woman suffering from buttock pain due to breast cancer metastases in the SI joint. We treated this patient with PRF neuromodulation of the L4-S3 primary dorsal rami and lateral branches using a rotating curved needle technique. The patient tolerated the procedures well, without any complications. She experienced about 70% reduction in pain, and pain relief was sustained for 10 months. This result suggests that PRF neuromodulation is a safe, effective treatment for pain from SI joint metastases. PMID- 26839673 TI - A Modified Approach of Percutaneous Endoscopic Lumbar Discectomy (PELD) for Far Lateral Disc Herniation at L5-S1 with Foot Drop. AB - Foraminal or extraforaminal Far Lateral Disc Herniations (FLDH) extending into or beyond the foraminal zone have been recognized as between 7-12% of all lumbosacral disc herniations. Conventional posterior laminectomy may not provide good access to a herniation that lies far lateral to the lateral margin of the pedicle. Use of the endoscopic technique through a percutaneous approach to treat such FLDH patients can decrease the surgical morbidity while achieving better outcomes. We made an effort to utilize the advantages of percutaneous endoscopic lumbar discectomy (PELD) and to determine the appropriate approach for FLDH at the level between the 5th Lumbar and first Sacral vertebrae(L5-S1). The authors present a case of an endoscopically resected lumbar extruded disc of the left extraforaminal zone with superior foraminal migration at the level of L5-S1, which had led to foot drop, while placing the endoscope in the anterior epidural space without facetectomy. PMID- 26839674 TI - Erratum: Review of Medical Dispute Cases in the Pain Management in Korea: A Medical Malpractice Liability Insurance Database Study. AB - [This corrects the article on p. 254 in vol. 28, PMID: 26495080.]. PMID- 26839676 TI - Moral distress and perception of futile care in intensive care nurses. AB - Special characteristics of care environments have always presented nurses with some challenges. One particular situation is futile care, which is frequently accompanied by countless moral and legal challenges. The dominant atmosphere in futile care may cause moral distress to nurses and lead to a sense of guilt, pain, suffering, job dissatisfaction, and eventually cause nurses to leave the job. This descriptive-analytical study attempted to investigate the relationship between futile care and moral distress in intensive care nurses. Study subjects were 300 nurses in intensive care units in Kerman, Iran and were selected by convenience sampling based on inclusion criteria. Study tools included Corley's 21-item questionnaire on moral distress and a researcher-made 17-item questionnaire on futile care. Data analysis was performed using SPSS version 16 and suitable analytical and descriptive tests. The results showed a significantly positive relationship between moral distress and futile care (P = 0.03, r = 0.4). Based on the obtained results, futile care can create conditions that may lead to moral distress in nurses and therefore strategies should be devised to prevent these conditions. Moreover, distress in nurses should be identified by periodical counseling so that it can be managed more efficiently. PMID- 26839675 TI - Ethical challenges in the neonatal intensive care units: perceptions of physicians and nurses; an Iranian experience. AB - The challenging nature of neonatal medicine today is intensified by modern advances in intensive care and treatment of sicker neonates. These developments have caused numerous ethical issues and conflicts in ethical decision-making. The present study surveyed the challenges and dilemmas from the viewpoint of the neonatal intensive care personnel in the teaching hospitals of Tehran University of Medical Sciences (TUMS) in the capital of Iran. In this comparative cross sectional study conducted between March 2013 and February 2014, the physicians' and nurses' perceptions of the ethical issues in neonatal intensive care units were compared. The physicians and nurses of the study hospitals were requested to complete a 36-item questionnaire after initial accommodations. The study samples consisted of 284 physicians (36%) and nurses (64%). Content validity and internal consistency calculations were used to examine the psychometric properties of the questionnaire. Data were analyzed by Pearson's correlation, t-test, ANOVA, and linear regression using SPSS v. 22. Respecting patients' rights and interactions with parents were perceived as the most challenging aspects of neonatal care. There were significant differences between sexes in the domains of the perceived challenges. According to the linear regression model, the perceived score would be reduced 0.33 per each year on the job. The results of our study showed that the most challenging issues were related to patients' rights, interactions with parents, communication and cooperation, and end of life considerations respectively. It can be concluded, therefore, that more attention should be paid to these issues in educational programs and ethics committees of hospitals. PMID- 26839677 TI - Professionalism in residents of physical medicine and rehabilitation in Iran. AB - Professionalism is the foundation of trust on which the doctor-patient relationship is built. This study was performed to measure professionalism in Iranian physical medicine and rehabilitation residents as a baseline assessment tool for future studies. This was a descriptive study. The Persian version of the American Board of Internal Medicine (ABIM) questionnaire was distributed among all the second and third-year residents of the medical state universities of Iran (n=43). Data were summarized as mean (SD), and independent samples t-test was used for comparison of means between genders, and also between the second and third-year residents. Forty questionnaires were analyzed. The mean (+/- SD) age of respondents was 29.95 (+/- 2.37) years. The mean score (SD) for the overall score was 115.15 (+/- 17.36) out of 150, and the mean score (+/- SD) for all items was 7.67 (+/- 1.15) out of 10. The respondents averaged 5.88 (+/- 1.69) for items forming the 'excellence' factor, 7.98 (+/- 1.48) for items in 'altruism/respect' and 8.92 (+/- 1.26) for items in the 'honor/integrity' subscale. These data may serve as a baseline for future research in this field. The lowest score pertained to excellence, which needs more focus in future studies. PMID- 26839678 TI - Moral self-concept and moral sensitivity in Iranian nurses. AB - Nurses are often faced with serious situations that require high levels of legal and ethical knowledge, and should therefore be sensitive to the moral issues in their profession in the decision making process. Some studies have investigated nurses' moral self-concept as an effective factor in moral sensitivity, but there is not sufficient evidence to support this. The purpose of this study was to determine the correlation between moral sensitivity and moral self-concept in nurses employed in the teaching hospitals in Zahedan, Iran. This cross-sectional descriptive study aimed to study the relationship between moral self-concept and moral sensitivity in nurses employed in the teaching hospitals affiliated with Zahedan University of Medical Sciences. Chang's Moral Self-Concept Questionnaire and Lutzen's Moral Sensitivity Questionnaire were used for data collection. Data analysis was performed using SPSS software version 17. A total of 188 nurses participated in this study. The results showed that there was a positive and significant relationship between moral self-concept and moral sensitivity (P < 0.05). Based on our findings, an individual's attention to moral issues can lead to greater sensitivity and result in morally responsible behavior at the time of decision making. Consequently, promotion of moral self-concept through personal effort or education can increase moral sensitivity, which in turn leads to behavioral manifestations of ethical knowledge. PMID- 26839679 TI - Developing an ethical guideline for clinical teaching in Tehran University of Medical Sciences. AB - Clinical education is an essential part of medical trainees' education process, and curriculum planners agree that it should be based on ethical standards and principles in the medical field. Nevertheless, no explained and codified criteria have been developed for ethics in clinical teaching. This study was aimed to develop an ethical guideline for medical students and teachers as the first and most important step in respecting patients' rights in educational centers. The initial draft included the codes of ethics in clinical education and was developed based on library studies. Subsequently, it was improved through a qualitative study using semi-structured interviews and focus group sessions with medical students, patients, and medical teachers in educational hospitals affiliated to Tehran University of Medical Sciences. The improved draft was reviewed and validated by a medical expert panel to prepare the final draft. The codes derived from this study included patients' choices and rights in purely educational procedures, and special considerations for a) obtaining informed consent for educational procedures; b) performing procedures on deceased persons, patients under anesthesia and those lacking decision making capacity; c) educational visual recordings of the patients; and d) safety monitoring in clinical education. The guideline developed in this study incorporates codes of ethics into clinical training. Therefore, in addition to providing efficient education, the interests of patients and their rights are respected, and the ethical sensitivity of learners in primacy of patients' best interests will be preserved and enhanced. PMID- 26839680 TI - Restored expression of vitamin D receptor and sensitivity to 1,25 dihydroxyvitamin D3 in response to disrupted fusion FOP2-FGFR1 gene in acute myeloid leukemia cells. AB - BACKGROUND: Acute myeloid leukemia (AML) cells can be induced to undergo terminal differentiation with subsequent loss of tumorigenicity using 1,25 dihydroxyvitamin D3 (1,25D) alone or in combination with hematopoietic cytokines. KG1 cells are resistant to 1,25D-induced cell differentiation. These cells have the aberrant signal transduction resulting from a constitutively active fusion protein FOP2-FGFR1, a constitutively active STAT1 and a high level of interferon (IFN) stimulated genes (ISGs). METHODS: In this paper we report that in KG1 cells with constitutively activated protein FOP2-FGFR1 delivery of plasmid DNA disrupted FOP2-FGFR1 fusion gene. RESULTS: As a consequence, STAT1 signal transduction pathway became switched off, the expression of vitamin D receptor (VDR) gene was increased and sensitivity to 1,25D-induced differentiation was restored. The activation of ISGs in KG1 cells resulted in resistance to externally added IFNs, and also this effect was reversed in cells with disrupted FOP2-FGFR1 fusion gene. DISCUSSION: In this paper we have documented for the first time a link between constitutively active STAT1 signal transduction pathway, high level of ISGs and low expression of VDR gene. CONCLUSIONS: We show in this paper that delivery of plasmid DNA to the cells may disrupt fusion gene FOP2-FGFR1 which occurs in a disease entity called 8p11 myeloproliferative syndrome. Inhibition of the FOP2-FGFR1 signal transduction pathway restored sensitivity of the cells to 1,25D-induced cell differentiation. PMID- 26839681 TI - Vaccine hesitancy: understanding better to address better. AB - Vaccine hesitancy is an emerging term in the socio-medical literature which describes an approach to vaccine decision making. It recognizes that there is a continuum between full acceptance and outright refusal of some or all vaccines and challenges the previous understanding of individuals or groups, as being either anti-vaccine or pro-vaccine. The behaviours responsible for vaccine hesitancy can be related to confidence, convenience and complacency. The causes of vaccine hesitancy can be described by the epidemiological triad i.e. the complex interaction of environmental- (i.e. external), agent- (i.e. vaccine) and host (or parent)- specific factors. Vaccine hesitancy is a complex and dynamic issue; future vaccination programs need to reflect and address these context specific factors in both their design and evaluation. Many experts are of the view that it is best to counter vaccine hesitancy at the population level. They believe that it can be done by introducing more transparency into policy decision making before immunization programs, providing up-to-date information to the public and health providers about the rigorous procedures undertaken before introduction of new vaccines, and through diversified post-marketing surveillance of vaccine-related events. PMID- 26839682 TI - An accelerated dose escalation with a grass pollen allergoid is safe and well tolerated: a randomized open label phase II trial. AB - BACKGROUND: The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. METHODS: In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. RESULTS: Treatment-related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty-eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". CONCLUSIONS: The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation. PMID- 26839683 TI - The use of Hardy-Weinberg Equilibrium in clonal plant systems. AB - Traditionally population genetics precludes the use of the same genetic individual more than once in Hardy-Weinberg (HW) based calculations due to the model's explicit assumptions. However, when applied to clonal plant populations this can be difficult to do, and in some circumstances, it may be ecologically informative to use the ramet as the data unit. In fact, ecologists have varied the definition of the individual from a strict adherence to a single data point per genotype to a more inclusive approach of one data point per ramet. With the advent of molecular tools, the list of facultatively clonal plants and the recognition of their ecological relevance grows. There is an important risk of misinterpretation when HW calculations are applied to a clonal plant not recognized as clonal, as well as when the definition of the individual for those calculations is not clearly stated in a known clonal species. Focusing on heterozygosity values, we investigate cases that demonstrate the extreme range of potential modeling outcomes and describe the different contexts where a particular definition could better meet ecological modeling goals. We emphasize that the HW model can be ecologically relevant when applied to clonal plants, but caution is necessary in how it is used, reported, and interpreted. We propose that in known clonal plants, both genotype (GHet) and ramet (RHet) based calculations are reported to define the full range of potential values and better facilitate cross-study comparisons. PMID- 26839684 TI - Response of pest control by generalist predators to local-scale plant diversity: a meta-analysis. AB - Disentangling the effects of plant diversity on the control of herbivores is important for understanding agricultural sustainability. Recent studies have investigated the relationships between plant diversity and arthropod communities at the landscape scale, but few have done so at the local scale. We conducted a meta-analysis of 32 papers containing 175 independent measures of the relationship between plant diversity and arthropod communities. We found that generalist predators had a strong positive response to plant diversity, that is, their abundance increased as plant diversity increased. Herbivores, in contrast, had an overall weak and negative response to plant diversity. However, specialist and generalist herbivores differed in their response to plant diversity, that is, the response was negative for specialists and not significant for generalists. While the effects of scale remain unclear, the response to plant diversity tended to increase for specialist herbivores, but decrease for generalist herbivores as the scale increased. There was no clear effect of scale on the response of generalist predators to plant diversity. Our results suggest that the response of herbivores to plant diversity at the local scale is a balance between habitat and trophic effects that vary according to arthropod specialization and habitat type. Synthesis and applications. Positive effects of plant diversity on generalist predators confirm that, at the local scale, plant diversification of agroecosystems is a credible and promising option for increasing pest regulation. Results from our meta-analysis suggest that natural control in plant-diversified systems is more likely to occur for specialist than for generalist herbivores. In terms of pest management, our results indicate that small-scale plant diversification (via the planting of cover crops or intercrops and reduced weed management) is likely to increase the control of specialist herbivores by generalist predators. PMID- 26839685 TI - Female Salix viminalis are more severely infected by Melampsora spp. but neither sex experiences associational effects. AB - Associational effects of plant genotype or species on plant biotic interactions are common, not least for disease spread, but associational effects of plant sex on interactions have largely been ignored. Sex in dioecious plants can affect biotic interactions with herbivores and pollinators; however, its effects on plant-pathogen interactions are understudied and associational effects are unknown. In a replicated field experiment, we assessed Melampsora spp. leaf rust infection in monosexual and mixed sex plots of dioecious Salix viminalis L. to determine whether plant sex has either direct or associational effects on infection severity. We found no differences in Melampsora spp. infection severity among sexual monocultures and mixtures in our field experiment. However, female plants were overall more severely infected. In addition, we surveyed previous studies of infection in S. viminalis clones and reevaluated the studies after we assigned sex to the clones. We found that females were generally more severely infected, as in our field study. Similarly, in a survey of studies on sex-biased infection in dioecious plants, we found more female-biased infections in plant pathogen pairs. We conclude that there was no evidence for associational plant sex effects of neighboring conspecifics for either females or males on infection severity. Instead, plant sex effects on infection act at an individual plant level. Our findings also suggest that female plants may in general be more severely affected by fungal pathogens than males. PMID- 26839686 TI - Intraspecific variation in seed dispersal of a Neotropical tree and its relationship to fruit and tree traits. AB - The distribution of wind-dispersed seeds around a parent tree depends on diaspore and tree traits, as well as wind conditions and surrounding vegetation. This study of a neotropical canopy tree, Platypodium elegans, explored the extent to which parental variation in diaspore and tree traits explained (1) rate of diaspore descent in still air, (2) distributions of diaspores dispersed from a 40 m tower in the forest, and (3) natural diaspore distributions around the parent tree. The geometric mean rate of descent in still air among 20 parents was highly correlated with geometric mean wing loading(1/2) (r = 0.84). However, diaspore traits and rate of descent predicted less variation in dispersal distance from the tower, although descent rate(-1) consistently correlated with dispersal distance. Measured seed shadows, particularly their distribution edges, differed significantly among six parents (DBH range 62-181 cm) and were best fit by six separate anisotropic dispersal kernels and surveyed fecundities. Measured rate of descent and tree traits, combined in a mechanistic seed dispersal model, did not significantly explain variation among parents in natural seed dispersal distances, perhaps due to the limited power to detect effects with only six trees. Seedling and sapling distributions were at a greater mean distance from the parents than seed distributions; saplings were heavily concentrated at far distances. Variation among parents in the distribution tails so critical for recruitment could not be explained by measured diaspore or tree traits with this sample size, and may be determined more by wind patterns and the timing of abscission in relation to wind conditions. Studies of wind dispersal need to devote greater field efforts at recording the "rare" dispersal events that contribute to far dispersal distances, following their consequences, and in understanding the mechanisms that generate them. PMID- 26839687 TI - Fluctuating selection on basal metabolic rate. AB - BMR (Basal metabolic rate) is an important trait in animal life history as it represents a significant part of animal energy budgets. BMR has also been shown to be positively related to sustainable work rate and maximal thermoregulatory capacity. To this date, most of the studies have focused on the causes of interspecific and intraspecific variation in BMR, and fairly little is known about the fitness consequences of different metabolic strategies. In this study, we show that winter BMR affects local survival in a population of wild blue tits (Cyanistes caeruleus), but that the selection direction differs between years. We argue that this fluctuating selection is probably a consequence of varying winter climate with a positive relation between survival and BMR during cold and harsh conditions, but a negative relation during mild winters. This fluctuating selection can not only explain the pronounced variation in BMR in wild populations, but will also give us new insights into how energy turnover rates can shape the life-history strategies of animals. Furthermore, the study shows that the process of global warming may cause directional selection for a general reduction in BMR, affecting the general life-history strategy on the population level. PMID- 26839688 TI - Morphometric traits capture the climatically driven species turnover of 10 spruce taxa across China. AB - This study explored the relative roles of climate and phylogenetic background in driving morphometric trait variation in 10 spruce taxa in China. The study further addressed the hypothesis that these variations are consistent with species turnover on climatic gradients. Nine morphometric traits of leaves, seed cones, and seeds for the 10 studied spruce taxa were measured at 504 sites. These data were analyzed in combination with species DNA sequences from NCBI GenBank. We detected the effects of phylogeny and climate through trait-variation-based K statistics and phylogenetic eigenvector regression (PVR) analyses. Multivariate analyses were performed to detect trait variation along climatic gradients with species replacement. The estimated K-values for the nine studied morphometric traits ranged from 0.19 to 0.68, and the studied environmental variables explained 39-83% of the total trait variation. Trait variation tended to be determined largely by a temperature gradient varying from wet-cool climates to dry-warm summers and, additionally, by a moisture gradient. As the climate became wetter and cooler, spruce species tended to be replaced by other spruces with smaller needle leaves and seeds but larger cones and seed scales. A regression analysis showed that spruce species tended to be successively replaced by other species, along the gradient, although the trends observed within species were not necessarily consistent with the overall trend. The climatically driven replacement of the spruces in question could be well indicated by the between species variation in morphometric traits that carry lower phylogenetic signal. Between-species variation in these traits is driven primarily by climatic factors. These species demonstrate a narrower ecological amplitude in temperature but wider ranges on the moisture gradient. PMID- 26839689 TI - Implications of recurrent disturbance for genetic diversity. AB - Exploring interactions between ecological disturbance, species' abundances and community composition provides critical insights for ecological dynamics. While disturbance is also potentially an important driver of landscape genetic patterns, the mechanisms by which these patterns may arise by selective and neutral processes are not well-understood. We used simulation to evaluate the relative importance of disturbance regime components, and their interaction with demographic and dispersal processes, on the distribution of genetic diversity across landscapes. We investigated genetic impacts of variation in key components of disturbance regimes and spatial patterns that are likely to respond to climate change and land management, including disturbance size, frequency, and severity. The influence of disturbance was mediated by dispersal distance and, to a limited extent, by birth rate. Nevertheless, all three disturbance regime components strongly influenced spatial and temporal patterns of genetic diversity within subpopulations, and were associated with changes in genetic structure. Furthermore, disturbance-induced changes in temporal population dynamics and the spatial distribution of populations across the landscape resulted in disrupted isolation by distance patterns among populations. Our results show that forecast changes in disturbance regimes have the potential to cause major changes to the distribution of genetic diversity within and among populations. We highlight likely scenarios under which future changes to disturbance size, severity, or frequency will have the strongest impacts on population genetic patterns. In addition, our results have implications for the inference of biological processes from genetic data, because the effects of dispersal on genetic patterns were strongly mediated by disturbance regimes. PMID- 26839691 TI - Successful treatment of cytomegalovirus associated hemophagocytic lymphohistiocytosis with the interleukin 1 inhibitor - anakinra. AB - Hemophagocytic lymphohistiocytosis (HLH) is a rare, frequently under-recognized condition associated with multi-organ failure and very high mortality. A 44-year old woman was admitted with a 4-day history of fever, headache, delirium, and dyspnea. She progressed rapidly to type 1 respiratory failure and required intubation and mechanical ventilation. Laboratory tests showed pancytopenia, abnormal liver enzyme levels, elevated triglyceride level, and elevated ferritin level. Bone marrow biopsy showed features of HLH. Computed tomography scan showed bilateral consolidation. Bronchoalveolar lavage was positive for cytomegalovirus. She was treated with ganciclovir, methylprednisolone, broad spectrum antibiotics, and cytomegalovirus hyperimmunoglobulin without clinical response. Given the poor prognosis and reports of success in pediatric HLH, anakinra 100 ug subcutaneously daily was commenced. There was rapid defervescence, resolution of delirium, and improvement in gas exchange, leading to complete recovery. This case illustrates successful treatment of HLH associated with cytomegalovirus pneumonitis with the interleukin 1 inhibitor anakinra. PMID- 26839690 TI - RNA-binding proteins in mouse male germline stem cells: a mammalian perspective. AB - Adult stem cells that reside in particular types of tissues are responsible for tissue homeostasis and regeneration. Cellular functions of adult stem cells are intricately related to the gene expression programs in those cells. Past research has demonstrated that regulation of gene expression at the transcriptional level can decisively alter cell fate of stem cells. However, cellular contents of mRNAs are sometimes not equivalent to proteins, the functional units of cells. It is increasingly realized that post-transcriptional and translational regulation of gene expression are also fundamental for stem cell functions. Compared to differentiated somatic cells, effects on cellular status manifested by varied expression of RNA-binding proteins and global protein synthesis have been demonstrated in several stem cell systems. Through the cooperation of both cis elements of mRNAs and trans-acting RNA-binding proteins that are intimately associated with them, regulation of localization, stability, and translational status of mRNAs directly influences the self-renewal and differentiation of stem cells. Previous studies have uncovered some of the molecular mechanisms that underlie the functions of RNA-binding proteins in stem cells in invertebrate species. However, their roles in adult stem cells in mammals are just beginning to be unveiled. This review highlights some of the RNA-binding proteins that play important functions during the maintenance and differentiation of mouse male germline stem cells, the adult stem cells in the male reproductive organ. PMID- 26839692 TI - Spontaneous regression of pulmonary metastatic melanoma. AB - Spontaneous regression of metastatic melanoma is a rare event with only 76 cases having been reported since 1866. The precise mechanism of regression remains unknown. We present a case of a man with spontaneous regression of pulmonary metastatic melanoma confirmed on histopathology accompanied by reduction in fluorodeoxyglucose-activity on serial positron emission tomography/computed tomography scan. PMID- 26839693 TI - Peripheral pulmonary carcinoid tumor diagnosed by endobronchial-ultrasound-guided bronchoscopy. AB - A 45-year-old Japanese woman complained of uncontrolled hypertension and face swelling. She was diagnosed with Cushing's syndrome with secretion of adrenocorticotropic hormone. Fluorodeoxyglucose positron emission tomography computed tomography revealed a 2 * 2 cm mass in her left lung, with high standardized maximum uptake value. She underwent bronchoscopy with endobronchial ultrasound via a guide-sheath. Surgical resection of her left upper lung was performed, and pathological examination showed a typical carcinoid tumor. After lung resection, she recovered from her subjective symptoms. Diagnosis of peripheral carcinoid tumor of the lung is generally difficult. Here, we introduce a case of peripheral pulmonary carcinoid tumor diagnosed by endobronchial ultrasound-guided bronchoscopy. PMID- 26839694 TI - Acute exacerbation of combined pulmonary fibrosis and emphysema associated with Hermansky-Pudlak syndrome. AB - A 30-year-old male smoker with congenital amblyopia and oculocutaneous albinism was admitted to our hospital complaining of progressive dyspnea on exertion. Chest computed tomography images revealed diffuse reticular opacities and honeycombing in the bilateral lower lobes with sparing of the subpleural region along with emphysema predominantly in the upper lobes. Lung biopsy specimens showed a mixture of usual interstitial pneumonia and a non-specific interstitial pneumonia pattern with emphysema. Of note, cuboidal epithelial cells with foamy cytoplasm on the alveolar walls and phagocytic macrophages with ceroid pigments in the fibrotic lesions were observed. The patient was diagnosed with Hermansky Pudlak syndrome (HPS) associated with combined pulmonary fibrosis and emphysema (CPFE). Six years following the patient's initial admission to our hospital, he died from acute exacerbation (AE) of CPFE associated with HPS. This is one of only few reports available on the clinicopathological characteristics of AE in CPFE associated with HPS. PMID- 26839695 TI - Hepatic hydrothorax without ascites as the first sign of liver cirrhosis. AB - A 60-year-old woman without a history of liver diseases, but with a history of regular alcohol consumption, presented with a right-sided transudative pleural effusion. Neither parenchymal lung lesion nor pleural thickening was seen on a chest computed tomography. On abdominal ultrasonography, the liver size and contour were normal, and ascites was not noted. Despite performing imaging and laboratory studies, we could not find a cause of the pleural effusion. Thus, due to her history of regular alcohol consumption, we decided to measure liver stiffness using a transient elastography (Fibroscan((r)), Echosens(TM), Paris, France), which showed a value of 35.3 kPa suggestive of liver cirrhosis. An intraperitoneal injection of a radioisotope demonstrated the transdiaphragmatic flow of fluid from peritoneal cavity to pleural cavity. The diagnosis was confirmed as hepatic hydrothorax. Management consisting of restricted salt and water intake with diuretics resulted in resolution of the hepatic hydrothorax. PMID- 26839696 TI - Pregnancy with hypoplastic left lung complicated by pneumothorax and pulmonary embolism. AB - We report a case of a 34-year-old lady with past history of asthma and pulmonary tuberculosis, who presented 5 weeks pregnant with acute dyspnea. Her chest X-ray showed left-sided complete lung collapse and concomitant right-sided pneumothorax. The pneumothorax was initially managed conservatively with a chest tube but due to its persistence despite suction, was subsequently changed to a Pneumostat(TM), with which she was later discharged. She had a normal echocardiography (ejection fraction [EF] 67%) at 5 weeks of gestation but developed pulmonary hypertension (EF 55%, pulmonary arterial pressure 40.7 mmHg) as the pregnancy progressed. She delivered a healthy baby at 35 weeks via elective lower section caesarean section with spinal anesthesia. We followed her up postnatally and noted the presence of left-sided pulmonary embolism, hypoplastic left lung, and left pulmonary artery. The management of this complex case involved a multidisciplinary effort between general medical, respiratory, obstetric, and cardiothoracic teams. PMID- 26839697 TI - IgG4-related disease in asbestos-related pleural disease. AB - A 67-year-old man with a history of asbestos exposure and rounded atelectasis complained of cough and swelling in the left submandibular region. Computed tomography showed an increase in size of the right lower lung lobe lesion, which was recognized as the pre-existing rounded atelectasis, as well as swelling of the pancreas and submandibular glands. Biopsy from a submandibular gland and the pulmonary lesion led to a diagnosis of immunoglobulin G4-related disease (IgG4 RD). IgG4-RD is a recently recognized disease that was first reported as an autoimmune disease; however, some reports have indicated another pathogenesis of an allergic nature that is characterized by type 2 helper T cell (Th2) inflammation. Additionally, it is recognized that long-term exposure to asbestos can cause immune dysregulation. Here we present a case of IgG4-RD associated with asbestos-related pleural disease. Asbestos-induced immune dysregulation may be one etiology of IgG4-RD. PMID- 26839698 TI - Nitrofurantoin-induced acute pulmonary toxicity. AB - We report a case of a female admitted to the emergency department with fever and severe type I acute respiratory failure. After detailed examination, all other potential causes were excluded and the patient was diagnosed with nitrofurantoin induced acute pulmonary toxicity. PMID- 26839699 TI - Repetitive responses to nanoparticle albumin-bound paclitaxel and carboplatin in malignant pleural mesothelioma. AB - Malignant pleural mesothelioma (MPM) is a rare tumor with a poor prognosis. Although cisplatin plus pemetrexed is the standard chemotherapy for patients with unresectable MPM, few agents are available for MPM patients who do not tolerate pemetrexed. Here, we report the first case of an MPM patient for whom the combination of nanoparticle albumin-bound paclitaxel and carboplatin (nabPC) repetitively achieved tumor regression. A 76-year-old man was diagnosed with epithelioid MPM. One cycle of carboplatin plus pemetrexed and two cycles of gemcitabine were administered but failed to inhibit tumor progression. By contrast, four cycles of nabPC resulted in a good response. Upon disease progression, four cycles of nabPC were performed again and resulted in a modest response. In conclusion, based on the present case, nabPC is a potential alternative chemotherapeutic agent for MPM, especially for MPM patients who do not tolerate pemetrexed. PMID- 26839700 TI - Invasive tracheobronchial aspergillosis progressing from bronchial to diffuse lung parenchymal lesions. AB - Invasive tracheobronchial aspergillosis that is entirely limited or predominantly confined to tracheobronchial lesions is a relatively rare form of invasive pulmonary aspergillosis. Extended parenchymal opacities that are radiological manifestations of invasive aspergillosis sometimes occur following invasive tracheobronchial aspergillosis. However, it remains unclear whether or not invasive tracheobronchial aspergillosis is the initial stage of invasive pulmonary aspergillosis. A 61-year-old woman was admitted because of severe diarrhea and dehydration. Three days after admission, she complained of dyspnea. A computed tomography (CT) scan of the chest showed bronchial wall thickening. She developed respiratory failure despite antibiotic therapy. A CT scan showed obstructions of bronchial lumens and bronchiectasis in the right upper lobe. A spergillus fumigatus was identified from samples obtained in bronchoscopic examination. Bronchial lesions rapidly progressed to be extended. A spergillus infection with multiple parenchymal opacities was observed on CT scan. She responded to treatment with antifungal drugs. PMID- 26839701 TI - Assessment of tetracycline contamination in surface and groundwater resources proximal to animal farming houses in Tehran, Iran. AB - BACKGROUND: Antibiotics have been increasingly used for veterinary and medical purposes. The overuse of these compounds for these purposes can pollute the environment, water resources in particular. Tetracycline, among other forms of antibiotics, is one of the most applied antibiotic in aquaculture and veterinary medicine. The present study aimed to tack the traces of tetracycline in the effluents of municipal and hospital wastewater treatment plants, surface and groundwater resources and finally the drinking water provided from these water resources. METHODS: The samples were taken from Fasha-Foyeh Dam, wells located at Varamin Plain, and Yaftabad; and also, wastewater samples were collected from the wastewater treatment plant effluents of Emam Khomeini Hospital and a municipal wastewater treatment plant which its effluent is being released to the surface water of the area covered in this work. 24 samples were collected in total during July 2012 to December 2012. The prepared samples were analyzed using high performance liquid chromatography. RESULTS: Based on the results, mean tetracycline levels in surface and ground water at nearby of animal farms was found to vary from 5.4 to 8.1 ng L(-1). Furthermore, the maximum TC concentration of 9.3 ng L(-1) was found to be at Yaft-Abad sampling station. Although tetracycline traces could not be detected in any investigated Hospital WWTP effluents, it was tracked in MWWTP effluent samples, in the concentration range of 280 to 540 ng l(-1). CONCLUSION: The results showed that the concentration of TC in water resource near the animal farms is higher than the other sampling stations. This is related to the usage of antibiotic for animals. In fact, it caused the contamination of water resources and could contribute to radical changes in the ecology of these regions. PMID- 26839702 TI - Benign hereditary chorea, not only chorea: a family case presentation. AB - BACKGROUND: Benign hereditary chorea is a rare disorder which is characterized by early onset, non-progressive choreic movement disturbance, with other hyperkinetic movements and unsteadiness also commonly seen. Hypothyroidism and lung disease are frequent additional features. The disorder is caused by mutations of the NKX2-1 gene on chromosome 14. CASE PRESENTATION: A Norwegian four-generation family with eight affected was identified. All family members had an early onset movement disorder, starting before one year of age with motor delay and chorea. Learning difficulties were commonly reported from early school years. The family presented with choreic movements at rest, but other movements were seen; myoclonus, dystonia, ataxia, stuttering and tics-like movements. All patients reported unsteadiness and ataxic gait was observed in two patients. Videos are provided in the supplementary material. Most affected family members had asthma and a subclinical or clinical hypothyroidism. Sequencing revealed a mutation in the NKX2-1 gene in all eight affected family members. CONCLUSIONS: This is the first Norwegian family with benign hereditary chorea due to a mutation in the NKX2-1 gene, c.671 T > G (p.Leu224Arg). This family demonstrates well the wide phenotype, including dystonia, myoclonus and ataxia. PMID- 26839704 TI - Telemedicine and E-Learning in a Primary Care Setting in Sudan: The Experience of the Gezira Family Medicine Project. AB - Information and communication technology (ICT) is progressively used in the health sector (e-health), to provide health care in a distance (telemedicine), facilitate medical education (e-learning), and manage patients' information (electronic medical records, EMRs). Gezira Family Medicine Project (GFMP) in Sudan provides a 2-year master's degree in family medicine, with ICT fully integrated in the project. This cross-sectional study describes ICT implementation and utilization at the GFMP for the years 2011-2012. Administrative data was used to describe ICT implementation, while questionnaire based data was used to assess candidates' perceptions and satisfaction. In the period from April 2011 to December 2012, 3808 telemedicine online consultations were recorded and over 165000 new patients' EMRs were established by the study subjects (125 candidates enrolled in the program). Almost all respondents confirmed the importance of telemedicine. The majority appreciated also the importance of using EMRs. Online lectures were highly rated by candidates in spite of the few challenges encountered by combining service provision with learning activity. Physicians highlighted some patients' concerns about the use of telemedicine and EMRs during clinical consultations. Results from this study confirmed the suitability of ICT use in postgraduate training in family medicine and in service provision. PMID- 26839706 TI - Reporting Melanoma: A Nationwide Surveillance of State Cancer Registries. AB - The goal of our study was to determine current melanoma reporting methods available to dermatologists and dermatopathologists and quantify changes in reporting methods from 2012 to 2014. A cross-sectional study design was utilized consisting of website perusal of reporting procedures, followed up by telephone and email inquiry of reporting methods from every state cancer registry. This study was conducted over a six-month period from February to August 2014. A previous similar survey was conducted in 2012 over the same time frame and results were compared. Kansas state cancer registry provided no data. As of August 2014, 96% of 49 state cancer registries had electronic methods available to all designated reporters. Seven (14%) states required an electronic-only method of reporting melanoma cases. Eighty-six percent allowed hard copy pathology report submission. Compared to the 2012 survey, 2 additional states were found to have initiated electronic reporting methods by 2014. In conclusion, a variety of methods exist for reporting diagnosed melanoma cases. Although most state cancer registries were equipped for electronic transmission of cases for mandated reporters, a number of states were ill-equipped for electronic submission from outpatient dermatologists. There was a general trend towards electronic versus nonelectronic reporting from 2012 to 2014. PMID- 26839705 TI - The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis. AB - Until recently, multiple sclerosis has been viewed as an entirely inflammatory disease without acknowledgment of the significant neurodegenerative component responsible for disease progression and disability. This perspective is being challenged by observations of a dissociation between inflammation and neurodegeneration where the neurodegenerative component may play a more significant role in disease progression. In this review, we explore the relationship between mitochondrial dysfunction and neurodegeneration in multiple sclerosis. We review evidence that the ketogenic diet can improve mitochondrial function and discuss the potential of the ketogenic diet in treating progressive multiple sclerosis for which no treatment currently exists. PMID- 26839703 TI - Evidence-Based Treatments for Adults with Migraine. AB - Migraine, a significantly disabling condition, is treated with acute and preventive medications. However, some individuals are refractory to standard treatments. Although there is a host of alternative management options available, these are not always backed by strong evidence. In fact, most of the drugs used in migraine were initially designed for other purposes. Whilst effective, the benefits from these medications are modest, reflecting the need for newer and migraine-specific therapeutic agents. In recent years, we have witnessed the emergence of novel treatments, of which noninvasive neuromodulation appears to be the most attractive given its ease of use and excellent tolerability profile. This paper reviews the evidence behind the available treatments for migraine. PMID- 26839707 TI - Prospects for Irradiation in Cellulosic Ethanol Production. AB - Second generation bioethanol production technology relies on lignocellulosic biomass composed of hemicelluloses, celluloses, and lignin components. Cellulose and hemicellulose are sources of fermentable sugars. But the structural characteristics of lignocelluloses pose hindrance to the conversion of these sugar polysaccharides into ethanol. The process of ethanol production, therefore, involves an expensive and energy intensive step of pretreatment, which reduces the recalcitrance of lignocellulose and makes feedstock more susceptible to saccharification. Various physical, chemical, biological, or combined methods are employed to pretreat lignocelluloses. Irradiation is one of the common and promising physical methods of pretreatment, which involves ultrasonic waves, microwaves, gamma-rays, and electron beam. Irradiation is also known to enhance the effect of saccharification. This review explains the role of different radiations in the production of cellulosic ethanol. PMID- 26839708 TI - Outcome following Resection of Biliary Cystadenoma: A Single Centre Experience and Literature Review. AB - Background. Biliary cystadenomas (BCAs) are rare, benign, potentially malignant cystic lesions of the liver, accounting for less than 5% of cystic liver tumours. We report the outcome following resection of biliary cystadenoma from a single tertiary centre. Methods. Data of patients who had resection of BCA between January 1993 and July 2014 were obtained from liver surgical database. Patient demographics, clinicopathological characteristics, operative data, and postoperative outcome were analysed. Results. 29 patients had surgery for BCA. Male : female ratio was 1 : 28. Clinical presentation was abdominal pain (74%), jaundice (20%), abdominal mass (14%), and deranged liver function tests (3%). Cyst characteristics included septations (48%), wall thickening (31%), wall irregularity (38%), papillary projections (10%), and mural nodule (3%). Surgical procedures included atypical liver resection (52%), left hemihepatectomy (34%), right hemihepatectomy (10%), and left lateral segmentectomy (3%). Median length of stay was 7 (IQ 6.5-8.5) days. Two patients developed postoperative bile leak. No patients had malignancy on final histology. Median follow-up was 13 (IQ 6.5 15.7) years. One patient developed delayed biliary stricture and one died of cholangiocarcinoma 11 years later. Conclusion. Biliary cystadenomas can be resected safely with significantly low morbidity. Malignant transformation and recurrence are rare. Complete surgical resection provides a cure. PMID- 26839709 TI - The Role of Adult-Born Neurons in the Constantly Changing Olfactory Bulb Network. AB - The adult mammalian brain is remarkably plastic and constantly undergoes structurofunctional modifications in response to environmental stimuli. In many regions plasticity is manifested by modifications in the efficacy of existing synaptic connections or synapse formation and elimination. In a few regions, however, plasticity is brought by the addition of new neurons that integrate into established neuronal networks. This type of neuronal plasticity is particularly prominent in the olfactory bulb (OB) where thousands of neuronal progenitors are produced on a daily basis in the subventricular zone (SVZ) and migrate along the rostral migratory stream (RMS) towards the OB. In the OB, these neuronal precursors differentiate into local interneurons, mature, and functionally integrate into the bulbar network by establishing output synapses with principal neurons. Despite continuous progress, it is still not well understood how normal functioning of the OB is preserved in the constantly remodelling bulbar network and what role adult-born neurons play in odor behaviour. In this review we will discuss different levels of morphofunctional plasticity effected by adult-born neurons and their functional role in the adult OB and also highlight the possibility that different subpopulations of adult-born cells may fulfill distinct functions in the OB neuronal network and odor behaviour. PMID- 26839710 TI - Lipidomic Analysis of Endocannabinoid Signaling: Targeted Metabolite Identification and Quantification. AB - The endocannabinoids N-arachidonoylethanolamide (or anandamide, AEA) and 2 arachidonoylglycerol (2-AG) belong to the larger groups of N-acylethanolamines (NAEs) and monoacylglycerol (MAG) lipid classes, respectively. They are biologically active lipid molecules that activate G-protein-coupled cannabinoid receptors found in various organisms. After AEA and 2-AG were discovered in the 1990s, they have been extensively documented to have a broad range of physiological functions. Along with AEA, several NAEs, for example, N palmitoylethanolamine (PEA), N-stearoylethanolamine (SEA), and N oleoylethanolamine (OEA) are also present in tissues, usually at much larger concentrations than AEA. Any perturbation that involves the endocannabinoid pathway may subsequently alter basal level or metabolism of these lipid mediators. Further, the altered levels of these molecules often reflect pathological conditions associated with tissue damage. Robust and sensitive methodologies to analyze these lipid mediators are essential to understanding how they act as endocannabinoids. The recent advances in mass spectrometry allow researchers to develop lipidomics approaches and several methodologies have been proposed to quantify endocannabinoids in various biological systems. PMID- 26839711 TI - Interpreting Intervention Induced Neuroplasticity with fMRI: The Case for Multimodal Imaging Strategies. AB - Direct measurement of recovery from brain injury is an important goal in neurorehabilitation, and requires reliable, objective, and interpretable measures of changes in brain function, referred to generally as "neuroplasticity." One popular imaging modality for measuring neuroplasticity is task-based functional magnetic resonance imaging (t-fMRI). In the field of neurorehabilitation, however, assessing neuroplasticity using t-fMRI presents a significant challenge. This commentary reviews t-fMRI changes commonly reported in patients with cerebral palsy or acquired brain injuries, with a focus on studies of motor rehabilitation, and discusses complexities surrounding their interpretations. Specifically, we discuss the difficulties in interpreting t-fMRI changes in terms of their underlying causes, that is, differentiating whether they reflect genuine reorganisation, neurological restoration, compensation, use of preexisting redundancies, changes in strategy, or maladaptive processes. Furthermore, we discuss the impact of heterogeneous disease states and essential t-fMRI processing steps on the interpretability of activation patterns. To better understand therapy-induced neuroplastic changes, we suggest that researchers utilising t-fMRI consider concurrently acquiring information from an additional modality, to quantify, for example, haemodynamic differences or microstructural changes. We outline a variety of such supplementary measures for investigating brain reorganisation and discuss situations in which they may prove beneficial to the interpretation of t-fMRI data. PMID- 26839712 TI - Increased N-Ethylmaleimide-Sensitive Factor Expression in Amygdala and Perirhinal Cortex during Habituation of Taste Neophobia. AB - Interactions between GluR2 and N-ethylmaleimide-sensitive factor (NSF) mediate AMPA receptors trafficking. This might be linked with molecular mechanisms related with memory formation. Previous research has shown basolateral amygdala (BLA) dependent activity changes in the perirhinal cortex (PRh) during the formation of taste memory. In the present experiments we investigate both the behavioral performance and the expression profile of NSF and GluR2 genes in several brain areas, including PRh, BLA, and hippocampus. Twenty-one naive male Wistar rats were exposed to a saccharin solution (0.4%) during the first (novel), the second (Familiar I), and the sixth presentation (Familiar II). Total RNA was extracted and gene expression was measured by quantitative PCR (qPCR) using TaqMan gene expression assays. In addition the expression of the synaptic plasticity related immediate early genes, Homer 1 and Narp, was also assessed. We have found increased expression of NSF gene in BLA and PRh in Group Familiar I in comparison with Familiar II. No changes in the expression of GluR2, Homer 1, and Narp genes were found. The results suggest the relevance of a potential network in the temporal lobe for taste recognition memory and open new possibilities for understanding the molecular mechanisms mediating the impact of sensory experience on brain circuit function. PMID- 26839713 TI - Salivary Cortisol Levels and Depressive Symptomatology in Consumers and Nonconsumers of Self-Help Books: A Pilot Study. AB - The self-help industry generates billions of dollars yearly in North America. Despite the popularity of this movement, there has been surprisingly little research assessing the characteristics of self-help books consumers, and whether this consumption is associated with physiological and/or psychological markers of stress. The goal of this pilot study was to perform the first psychoneuroendocrine analysis of consumers of self-help books in comparison to nonconsumers. We tested diurnal and reactive salivary cortisol levels, personality, and depressive symptoms in 32 consumers and nonconsumers of self help books. In an explorative secondary analysis, we also split consumers of self help books as a function of their preference for problem-focused versus growth oriented self-help books. The results showed that while consumers of growth oriented self-help books presented increased cortisol reactivity to a psychosocial stressor compared to other groups, consumers of problem-focused self help books presented higher depressive symptomatology. The results of this pilot study show that consumers with preference for either problem-focused or growth oriented self-help books present different physiological and psychological markers of stress when compared to nonconsumers of self-help books. This preliminary study underlines the need for additional research on this issue in order to determine the impact the self-help book industry may have on consumers' stress. PMID- 26839714 TI - Polarity Determinants in Dendritic Spine Development and Plasticity. AB - The asymmetric distribution of various proteins and RNAs is essential for all stages of animal development, and establishment and maintenance of this cellular polarity are regulated by a group of conserved polarity determinants. Studies over the last 10 years highlight important functions for polarity proteins, including apical-basal polarity and planar cell polarity regulators, in dendritic spine development and plasticity. Remarkably, many of the conserved polarity machineries function in similar manners in the context of spine development as they do in epithelial morphogenesis. Interestingly, some polarity proteins also utilize neuronal-specific mechanisms. Although many questions remain unanswered in our understanding of how polarity proteins regulate spine development and plasticity, current and future research will undoubtedly shed more light on how this conserved group of proteins orchestrates different pathways to shape the neuronal circuitry. PMID- 26839715 TI - Dysfunction in Ribosomal Gene Expression in the Hypothalamus and Hippocampus following Chronic Social Defeat Stress in Male Mice as Revealed by RNA-Seq. AB - Chronic social defeat stress leads to the development of anxiety- and depression like states in male mice and is accompanied by numerous molecular changes in brain. The influence of 21-day period of social stress on ribosomal gene expression in five brain regions was studied using the RNA-Seq database. Most Rps, Rpl, Mprs, and Mprl genes were upregulated in the hypothalamus and downregulated in the hippocampus, which may indicate ribosomal dysfunction following chronic social defeat stress. There were no differentially expressed ribosomal genes in the ventral tegmental area, midbrain raphe nuclei, or striatum. This approach may be used to identify a pharmacological treatment of ribosome biogenesis abnormalities in the brain of patients with "ribosomopathies." PMID- 26839716 TI - Functional versus Nonfunctional Rehabilitation in Chronic Ischemic Stroke: Evidences from a Randomized Functional MRI Study. AB - Motor rehabilitation of stroke survivors may include functional and/or nonfunctional strategy. The present study aimed to compare the effect of these two rehabilitation strategies by means of clinical scales and functional Magnetic Resonance Imaging (fMRI). Twelve hemiparetic chronic stroke patients were selected. Patients were randomly assigned a nonfunctional (NFS) or functional (FS) rehabilitation scheme. Clinical scales (Fugl-Meyer, ARA test, and modified Barthel) and fMRI were applied at four moments: before rehabilitation (P1) and immediately after (P2), 1 month after (P3), and three months after (P4) the end of rehabilitation. The NFS group improved significantly and exclusively their Fugl-Meyer scores at P2, P3, and P4, when compared to P1. On the other hand, the FS group increased significantly in Fugl-Meyer at P2, when compared to P1, and also in their ARA and Barthel scores. fMRI inspection at the individual level revealed that both rehabilitation schemes most often led to decreased activation sparseness, decreased activity of contralesional M1, increased asymmetry of M1 activity to the ipsilesional side, decreased perilesional activity, and decreased SMA activity. Increased M1 asymmetry with rehabilitation was also confirmed by Lateralization Indexes. Our clinical analysis revealed subtle differences between FS and NFS. PMID- 26839717 TI - Altered ERK1/2 Signaling in the Brain of Learned Helpless Rats: Relevance in Vulnerability to Developing Stress-Induced Depression. AB - Extracellular signal-regulated kinase 1/2- (ERK1/2-) mediated cellular signaling plays a major role in synaptic and structural plasticity. Although ERK1/2 signaling has been shown to be involved in stress and depression, whether vulnerability to develop depression is associated with abnormalities in ERK1/2 signaling is not clearly known. The present study examined ERK1/2 signaling in frontal cortex and hippocampus of rats that showed vulnerability (learned helplessness, (LH)) or resiliency (non-learned helplessness, (non-LH)) to developing stress-induced depression. In frontal cortex and hippocampus of LH rats, we found that mRNA and protein expressions of ERK1 and ERK2 were significantly reduced, which was associated with their reduced activation and phosphorylation in cytosolic and nuclear fractions, where ERK1 and ERK2 target their substrates. In addition, ERK1/2-mediated catalytic activities and phosphorylation of downstream substrates RSK1 (cytosolic and nuclear) and MSK1 (nuclear) were also lower in the frontal cortex and hippocampus of LH rats without any change in their mRNA or protein expression. None of these changes were evident in non-LH rats. Our study indicates that ERK1/2 signaling is differentially regulated in LH and non-LH rats and suggests that abnormalities in ERK1/2 signaling may be crucial in the vulnerability to developing depression. PMID- 26839718 TI - Expression and Function of the Endocannabinoid System in the Retina and the Visual Brain. AB - Endocannabinoids are important retrograde modulators of synaptic transmission throughout the nervous system. Cannabinoid receptors are seven transmembrane G protein coupled receptors favoring Gi/o protein. They are known to play an important role in various processes, including metabolic regulation, craving, pain, anxiety, and immune function. In the last decade, there has been a growing interest for endocannabinoids in the retina and their role in visual processing. The purpose of this review is to characterize the expression and physiological functions of the endocannabinoid system in the visual system, from the retina to the primary visual cortex, with a main interest regarding the retina, which is the best-described area in this system so far. It will show that the endocannabinoid system is widely present in the retina, mostly in the through pathway where it can modulate neurotransmitter release and ion channel activity, although some evidence also indicates possible mechanisms via amacrine, horizontal, and Muller cells. The presence of multiple endocannabinoid ligands, synthesizing and catabolizing enzymes, and receptors highlights various pharmacological targets for novel therapeutic application to retinal diseases. PMID- 26839719 TI - Correlations between the Memory-Related Behavior and the Level of Oxidative Stress Biomarkers in the Mice Brain, Provoked by an Acute Administration of CB Receptor Ligands. AB - The endocannabinoid system, through cannabinoid (CB) receptors, is involved in memory-related responses, as well as in processes that may affect cognition, like oxidative stress processes. The purpose of the experiments was to investigate the impact of CB1 and CB2 receptor ligands on the long-term memory stages in male Swiss mice, using the passive avoidance (PA) test, as well as the influence of these compounds on the level of oxidative stress biomarkers in the mice brain. A single injection of a selective CB1 receptor antagonist, AM 251, improved long term memory acquisition and consolidation in the PA test in mice, while a mixed CB1/CB2 receptor agonist WIN 55,212-2 impaired both stages of cognition. Additionally, JWH 133, a selective CB2 receptor agonist, and AM 630, a competitive CB2 receptor antagonist, significantly improved memory. Additionally, an acute administration of the highest used doses of JWH 133, WIN 55,212-2, and AM 630, but not AM 251, increased total antioxidant capacity (TAC) in the brain. In turn, the processes of lipids peroxidation, expressed as the concentration of malondialdehyde (MDA), were more advanced in case of AM 251. Thus, some changes in the PA performance may be connected with the level of oxidative stress in the brain. PMID- 26839721 TI - Electrical Injury-Induced Complete Atrioventricular Block: Is Permanent Pacemaker Required? AB - A considerable percentage of electrical injuries occur as a result of work activities. Electrical injury can lead to various cardiovascular disorders: acute myocardial necrosis, myocardial ischemia, heart failure, arrhythmias, hemorrhagic pericarditis, acute hypertension with peripheral vasospasm, and anomalous, nonspecific ECG alterations. Ventricular fibrillation is the most common arrhythmia resulting from electrical injury and is the leading cause of death in electrical (especially low voltage alternating current) injury cases. Asystole, premature ventricular contractions, ventricular tachycardia, conduction disorders (various degrees of heart blocks, bundle-brunch blocks), supraventricular tachycardia, and atrial fibrillation are the other arrhythmic complications of electrical injury. Complete atrioventricular block has rarely been reported and permanent pacemaker was required for the treatment in some of these cases. Herein, we present a case of reversible complete atrioventricular block due to low voltage electrical injury in a young electrical technician. PMID- 26839722 TI - Persistent Hypoglycemia in Patient with Hodgkin's Disease. AB - Hypoglycemia is a rare complication of Hodgkin's disease. Several explanations have been postulated but the exact pathophysiology is not well understood. We are presenting a case of newly diagnosed Stage IV Hodgkin's disease that developed persistent and recurrent hypoglycemia despite giving glucagon, repeated 50% dextrose, and D5 and D10 continuous infusion. Hypoglycemia workup showed the C peptide level to be low. Patient was suspected of having hypoglycemia related to lymphoma and was given a trial of prednisone which resolved the hypoglycemic episodes and made the patient euglycemic for the rest of his hospital stay. The presence of a substance that mimicked the effects of insulin was highly suspected. Several case reports strengthen the hypothesis of an insulin-like growth factor or antibodies secreted by the cancer cells causing hypoglycemia in Hodgkin's disease but none of them have been confirmed. Further investigation is warranted to more clearly define the pathophysiology of persistent hypoglycemia in patients with Hodgkin's disease. PMID- 26839724 TI - Posttraumatic Sphingomonas paucimobilis Endophthalmitis. AB - A rare case of Sphingomonas paucimobilis endophthalmitis secondary to a penetrating globe injury with a retained intraocular foreign body is presented. A 30-year-old man presented with severe pain following a penetrating left eye injury. Visual acuity (VA) was 6/120. Slit-lamp examination revealed perforation of the temporal cornea and iris, hypopyon, and a fibrinous membrane covering the pupil. Ultrasonography showed dense vitreous infiltration and an orbital CT-scan confirmed the presence of a metallic foreign body in the vitreous cavity. Topical and systemic therapy were initiated. Pars-plana vitrectomy combined with phacoemulsification was performed in order to remove the foreign body; vitreous samples were acquired and Sphingomonas paucimobilis, sensitive to ceftazidime, was identified. To the best of our knowledge, this is the first report of Sphingomonas paucimobilis endophthalmitis following penetrating ocular injury. In this case, Sphingomonas paucimobilis was not resistant to antibiotics. This allowed for a good healing response following vitrectomy despite the fact that long-term retinal complications resulted in low VA. PMID- 26839723 TI - Bilateral Bronchiectasis as a Presentation Form of Pulmonary Marginal Zone B-Cell Lymphoma of Bronchus Associated Lymphoid Tissue. AB - The pulmonary marginal zone B-cell lymphoma of bronchus associated lymphoid tissue of the lung (BALT) is a rare illness that can remain without symptoms. Radiological findings of pulmonary lymphoma are heterogeneous. In literature, bronchiectasis is only described in one patient who also had besides adenomegalies. We reported on a 48-year-old female patient. She showed symptoms consistent with dyspnea with productive cough; there were crepitant sounds in the auscultation. Pulmonary functional test has shown a severe restrictive pattern with a low FVC and DLCO. CT scan showed bronchiectasis in the medium lobule without adenomegalies. Echocardiogram was normal, and the laboratory findings only showed leukocytosis. There were no findings in the bronchoscopy, but the lung biopsy showed a B-cell pulmonary lymphoma (positive to CD20 and CD79a in immunostaining). A wide variety of radiological manifestations has been previously described; however, we have presented this rare case, with bronchiectasis, as unique radiological finding. PMID- 26839725 TI - Bilateral Macular Roth Spots as a Manifestation of Subacute Endocarditis. AB - A 42-year-old man presented with a 2-day history of impaired vision in the right eye (OD). The best corrected visual acuity (BCVA) (LogMAR) was 1.1 for the right eye and 0.0 for the left eye (OS). Fundus examination revealed white-centered hemorrhages resembling Roth spots in both macular regions. The spectral-domain optical coherence tomography (SD-OCT) showed intraretinal pseudocysts and hyperreflective deposits in the areas corresponding to the Roth spots. Conducted blood tests revealed elevated D-dimer concentration, increased total number of neutrophils, high C-reactive protein concentration, and elevated erythrocyte sedimentation rate. Procalcitonin concentration, platelet count, and body temperature were within normal ranges. A blood culture was ordered and yielded Streptococcus mitis and intravenous antibiotics were started immediately. The patient started complaining of chest and left calf pain. The systemic examination revealed infective endocarditis accompanied by bicuspid aortic valve and paravalvular abscess formation. The patient underwent cardiac surgery with mechanical aortic valve implantation. After recovery, the patient's visual acuities improved fully. Control ophthalmic examination, including SD-OCT, showed no abnormalities. PMID- 26839726 TI - Intractable Posterior Epistaxis due to a Spontaneous Low-Flow Carotid-Cavernous Sinus Fistula: A Case Report and a Review of the Literature. AB - We report a case of a 90-year-old patient with intractable posterior epistaxis presenting as the only symptom of a nontraumatic low-flow carotid-cavernous sinus fistula. Purpose of this case report is to introduce low-flow carotid-cavernous sinus fistula in the differential diagnosis of intractable posterior epistaxis. We provide a literature review for the sequence of actions for the confrontation of posterior epistaxis. We also emphasize the significance of the radiological diagnostic and therapeutic procedures in the management of posterior epistaxis due to pathology of the cavernous sinus. The gold-standard diagnostic procedure of carotid-cavernous sinus fistula is digital subtraction angiography (DSA). DSA with coils is also the state-of-the-art therapy. By failure of DSA, neurosurgery or stereotactic radiosurgery (SRS) may be used as alternatives. SRS may also be used as enhancement procedure of the DSA. Considering the prognosis of a successfully closed carotid-cavernous sinus fistula, recanalization occurs only in a minority of patients. Close follow-up is advised. PMID- 26839727 TI - Humoral Immunity in Bronchiectasis: Finding Good's Syndrome. AB - We present a case of a 37-year-old man with a past history of a surgically removed thymoma, who presented with recurrent pulmonary infections and bronchiectasis. On further testing, he was found to have low total immunoglobulin levels, a constellation of findings known as Good's syndrome. He responded well to immunoglobulin replacement, in addition to the usual treatments for bronchiectasis. We present this case to emphasize the association of bronchiectasis, low immunoglobulins, and thymomas and the role of immunoglobulin replacement as a treatment option. PMID- 26839728 TI - Coexistence of Takayasu Arteritis and Crohn's Disease in a Maltese Patient. AB - Takayasu arteritis (TA) and Crohn's disease (CD) are uncommon chronic granulomatous disorders affecting the large arteries and the gastrointestinal tract, respectively. At least 40 occurrences of these two conditions in the same patient have been reported in the literature, raising the possibility of an association between them. We report the coexistence of TA and CD in a young Maltese patient and review the literature to discuss possible aetiological mechanisms that might explain this association. PMID- 26839729 TI - Intradural Intramedullary Mixed Type Hemangioma: Optimizing the Surgical Management through Intraoperative Neurophysiological Monitoring. AB - Intradural intramedullary mixed type hemangioma is a rare histotype of primary spinal cord tumors, though it can carry a severe clinical burden leading to limb dysfunction or motor and sensory disturbances. Timely intervention with radical resection is the hallmark of treatment but achieving it is not an easy task even for experienced neurosurgeons. We herein present an exemplificative case presenting with sudden paraplegia in which total resection was achieved under intraoperative neurophysiology monitoring. A thorough discussion on the operative technique and the role of neuromonitoring in allowing a safe surgical management of primary spinal cord tumors is presented. PMID- 26839720 TI - In Sickness and in Health: Perineuronal Nets and Synaptic Plasticity in Psychiatric Disorders. AB - Rapidly emerging evidence implicates perineuronal nets (PNNs) and extracellular matrix (ECM) molecules that compose or interact with PNNs, in the pathophysiology of several psychiatric disorders. Studies on schizophrenia, autism spectrum disorders, mood disorders, Alzheimer's disease, and epilepsy point to the involvement of ECM molecules such as chondroitin sulfate proteoglycans, Reelin, and matrix metalloproteases, as well as their cell surface receptors. In many of these disorders, PNN abnormalities have also been reported. In the context of the "quadripartite" synapse concept, that is, the functional unit composed of the pre and postsynaptic terminals, glial processes, and ECM, and of the role that PNNs and ECM molecules play in regulating synaptic functions and plasticity, these findings resonate with one of the most well-replicated aspects of the pathology of psychiatric disorders, that is, synaptic abnormalities. Here we review the evidence for PNN/ECM-related pathology in these disorders, with particular emphasis on schizophrenia, and discuss the hypothesis that such pathology may significantly contribute to synaptic dysfunction. PMID- 26839730 TI - Prostatic Stromal Tumor of Uncertain Malignant Potential Which Was Difficult to Diagnose. AB - Here, we report a case of stromal tumor of uncertain malignant potential (STUMP) that was difficult to diagnose. A 53-year-old male was found to have a hard nodule on digital rectal examination; magnetic resonance imaging revealed a large nodule on the left side of the prostate, indicating prostate cancer. However, pathological diagnosis of the biopsy specimen was benign prostatic hyperplasia. Although a papillary tumor in the prostatic urethra was also seen on urethrocystoscopy, the tumor specimen obtained from transurethral resection was not malignant. The tumor in the prostatic urethra recurred only 3 months after transurethral resection, and pathological findings revealed benign hyperplasia not only in the stromal tissue but also in the epithelium; therefore, the prostate tumor was suspected to be STUMP. It took many prostate pathologists a long time to reach the final diagnosis of STUMP. STUMP is a rare benign tumor, difficult to diagnose, and sometimes transforms into stromal sarcoma. Thus, we should consider radical resection in such cases. PMID- 26839732 TI - Acceptance and Utilisation of Sulphadoxine-Pyrimethamine and Insecticide-Treated Nets among Pregnant Women in Oyo State, Nigeria. AB - The study is an investigation of the acceptance and utilisation of Sulphadoxine Pyrimethamine (Fansidar), the drug of choice for Intermittent Preventive Treatment in pregnancy, and Insecticide-Treated Nets among pregnant women who access different health facilities in Oyo State, Nigeria. Pregnant women (582) attending government primary healthcare antenatal clinics and 50 attending faith clinics purposively selected responded to structured instruments that were analysed using percentages, t-test correlation, and multiple regression. Acceptance and utilisation of RBM tools were higher in government clinics than faith clinics and in rural areas. Pregnant women in government clinics, 60.8% and 66.8%, and faith clinics, 18% and 38.0%, utilised Roll Back Malaria tools, significant at t (630) = 5.81, p <= 0.05, and t (630) = 3.99, p <= 0.05, respectively. Pregnant women in rural locations who accessed government clinics utilised Roll Back Malaria tools more than those in urban areas, t (580) = -641, p <= 0.05. Number of pregnancies, educational qualification of the pregnant women, and marital status significantly and consistently influenced acceptance and utilisation of these tools. To ensure that set targets are met, the utilization of RBM tools among the two categories of pregnant women can be improved by increasing the supply of the tools and ensuring that treatment is free. PMID- 26839733 TI - Development and Validation of an HPLC Method for Simultaneous Quantification of Clopidogrel Bisulfate, Its Carboxylic Acid Metabolite, and Atorvastatin in Human Plasma: Application to a Pharmacokinetic Study. AB - A simple, sensitive, and specific reversed phase liquid chromatographic method was developed and validated for simultaneous quantification of clopidogrel, its carboxylic acid metabolite, and atorvastatin in human serum. Plasma samples were deproteinized with acetonitrile and ibuprofen was chosen as internal standard. Chromatographic separation was performed on an BDS Hypersil C18 column (250 * 4.6 mm; 5 MUm) via gradient elution with mobile phase consisting of 10 mM phosphoric acid (sodium) buffer solution (pH = 2.6 adjusted with 85% orthophosphoric acid) : acetonitrile : methanol with flow rate of 1 mL.min(-1). Detection was achieved with PDA detector at 220 nm. The method was validated in terms of linearity, sensitivity, precision, accuracy, limit of quantification, and stability tests. Calibration curves of the analytes were found to be linear in the range of 0.008 2 MUg.mL(-1) for clopidogrel, 0.01-4 MUg.mL(-1) for its carboxylic acid metabolite, and 0.005-2.5 MUg.mL(-1) for atorvastatin. The results of accuracy (as recovery) with ibuprofen as internal standard were in the range of 96-98% for clopidogrel, 94-98% for its carboxylic acid metabolite, and 90-99% for atorvastatin, respectively. PMID- 26839731 TI - Angiogenesis in Inflammatory Bowel Disease. AB - Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature. PMID- 26839734 TI - Validating the Voodoo Doll Task as a Proxy for Aggressive Parenting Behavior. AB - OBJECTIVE: Six studies (N = 1,081 general population parents) assessed the validity of the Voodoo Doll Task (VDT) as a proxy for aggressive parenting behaviors. METHODS: Participants were given an opportunity to symbolically inflict harm by choosing to stick "pins" into a doll representing their child. RESULTS: Individual differences in parents' trait aggression (Studies 1, 2, and 6), state hostility (Study 3), attitudes towards the corporal punishment of children (Study 4), self-control (Study 6), depression (Study 6), and child physical abuse risk (Study 6) were associated with increased pin usage. Further, parents used more pins after imagining their child perform negative behaviors compared to after imagining their child perform positive behaviors (Study 5). A number of demographic variables also were associated with pin usage: Fathers used pins more than mothers and parents' education level was inversely related to pin usage. Finally, on average, parents viewed the VDT as slightly uncomfortable, but not objectionable, to complete (Study 6). CONCLUSIONS: Our evidence suggests that the VDT may serve as a useful proxy for parent-to-child aggression. PMID- 26839735 TI - Reduced functional connectivity of somatosensory network in writer's cramp patients. AB - BACKGROUND: The involvement of motor cortex and sensorimotor integration in patients with writer's cramp (WC) has been well documented. However, the exact neurophysiological profile within the somatosensory system, including primary somatosensory cortex (SI), contralateral (SIIc), and ipsilateral (SIIi) secondary somatosensory areas remains less understood. METHODS: This study investigated the neuromagnetic cortical activities of median nerve stimulation in 10 patients with WC and 10 healthy controls (HC). To comprehensively explore all the aspects of somatosensory functioning, we analyzed our data with the minimum norm estimate (MNE), the time-frequency approach with evoked and induced activities, and functional connectivity between SI and SIIc (SI-SIIc), SI and SIIi (SI-SIIi), and SIIc and SIIi (SIIc-SIIi) from theta to gamma oscillations. RESULTS: No significant between-group differences were found in the MNE cortical amplitudes of SI, SIIc, and SIIi. Power strengths of evoked gamma oscillation and induced beta synchronization were also equivalent between WC and HC groups. However, we found significantly reduced theta coherence of SI-SIIi, alpha coherence of SI SIIi and SIIc-SIIi, as well as beta coherence of SIIc-SIIi in patients with WC. CONCLUSION: Our results suggest the involvement of somatosensory abnormalities, primarily with the form of functional connectivity, in patients with WC. PMID- 26839736 TI - Patterns of hydroxyurea use and clinical outcomes among patients with polycythemia vera in real-world clinical practice: a chart review. AB - BACKGROUND: Hydroxyurea (HU) is among the most commonly used cytoreductive treatments for polycythemia vera (PV), but previous research and clinical experience suggest that not all patients respond optimally, consistently, or durably to HU treatment. This study investigated patterns of HU use and impact on disease control among patients with PV in real-world clinical practice in the United States. METHODS: Oncologists and hematologists recruited between April and July 2014 reported data from patient charts. Treatment history and disease symptom comparisons between HU subgroups were performed using Chi square tests or one-way analyses of variance for categorical and continuous variables. Other analyses were performed using descriptive statistics. RESULTS: Overall, 329 physicians participated and provided data on 1309 patients with PV (62.3 % male; mean age = 62.5 years, mean time since diagnosis = 5.2 years). In the 229 (17.5 %) patients who had stopped HU, the most common reasons for HU discontinuation-as assessed by the treating clinician-were inadequate response (29.3 %), intolerance (27.5 %), and disease progression (12.7 %). Among patients currently on HU, a significant proportion had elevated blood cell counts: 34.4 % had hematocrit values >=45 %, 59.4 % had platelet levels >400 * 10(9)/L, and 58.2 % had WBC counts > 10 * 10(9)/L. Two-thirds (66.3 %) of patients had >=1 elevated count, 40.3 % had >=2 elevated counts, and 19.8 % had all 3 counts elevated. The most common PV-related signs and symptoms among all patients were fatigue and splenomegaly. CONCLUSIONS: Although many patients with PV benefit from HU therapy, some continue to have suboptimal control of their disease, as evidenced by persistence of abnormally elevated blood cell counts and the continued experience of disease-related manifestations (signs and symptoms). These data further denote a significant medical need for some patients with PV currently or previously treated with HU. PMID- 26839737 TI - Intermediate-term emotional bookkeeping is necessary for long-term reciprocal grooming partner preferences in an agent-based model of macaque groups. AB - Whether and how primates are able to maintain long-term affiliative relationships is still under debate. Emotional bookkeeping (EB), the partner-specific accumulation of emotional responses to earlier interactions, is a candidate mechanism that does not require high cognitive abilities. EB is difficult to study in real animals, due to the complexity of primate social life. Therefore, we developed an agent-based model based on macaque behavior, the EMO-model, that implements arousal and two emotional dimensions, anxiety-FEAR and satisfaction LIKE, which regulate social behavior. To implement EB, model individuals assign dynamic LIKE attitudes towards their group members, integrating partner-specific emotional responses to earlier received grooming episodes. Two key parameters in the model were varied to explore their effects on long-term affiliative relationships: (1) the timeframe over which earlier affiliation is accumulated into the LIKE attitudes; and (2) the degree of partner selectivity. EB over short and long timeframes gave rise to low variation in LIKE attitudes, and grooming partner preferences were only maintained over one to two months. Only EB over intermediate-term timeframes resulted in enough variation in LIKE attitudes, which, in combination with high partner selectivity, enables individuals to differentiate between regular and incidental grooming partners. These specific settings resulted in a strong feedback between differentiated LIKE attitudes and the distribution of grooming, giving rise to strongly reciprocated partner preferences that could be maintained for longer periods, occasionally up to one or two years. Moreover, at these settings the individual's internal, socio emotional memory of earlier affiliative episodes (LIKE attitudes) corresponded best to observable behavior (grooming partner preferences). In sum, our model suggests that intermediate-term LIKE dynamics and high partner selectivity seem most plausible for primates relying on emotional bookkeeping to maintain their social bonds. PMID- 26839738 TI - Marine microbial communities of the Great Barrier Reef lagoon are influenced by riverine floodwaters and seasonal weather events. AB - The role of microorganisms in maintaining coral reef health is increasingly recognized. Riverine floodwater containing herbicides and excess nutrients from fertilizers compromises water quality in the inshore Great Barrier Reef (GBR), with unknown consequences for planktonic marine microbial communities and thus coral reefs. In this baseline study, inshore GBR microbial communities were monitored along a 124 km long transect between 2011 and 2013 using 16S rRNA gene amplicon sequencing. Members of the bacterial orders Rickettsiales (e.g., Pelagibacteraceae) and Synechococcales (e.g., Prochlorococcus), and of the archaeal class Marine Group II were prevalent in all samples, exhibiting a clear seasonal dynamics. Microbial communities near the Tully river mouth included a mixture of taxa from offshore marine sites and from the river system. The environmental parameters collected could be summarized into four groups, represented by salinity, rainfall, temperature and water quality, that drove the composition of microbial communities. During the wet season, lower salinity and a lower water quality index resulting from higher river discharge corresponded to increases in riverine taxa at sites near the river mouth. Particularly large, transient changes in microbial community structure were seen during the extreme wet season 2010-11, and may be partially attributed to the effects of wind and waves, which resuspend sediments and homogenize the water column in shallow near shore regions. This work shows that anthropogenic floodwaters and other environmental parameters work in conjunction to drive the spatial distribution of microorganisms in the GBR lagoon, as well as their seasonal and daily dynamics. PMID- 26839739 TI - Impact of demographics on human gut microbial diversity in a US Midwest population. AB - The clinical utility of microbiome biomarkers depends on the reliable and reproducible nature of comparative results. Underappreciation of the variation associated with common demographic, health, and behavioral factors may confound associations of interest and generate false positives. Here, we present the Midwestern Reference Panel (MWRP), a resource for comparative gut microbiome studies conducted in the Midwestern United States. We analyzed the relationships between demographic and health behavior-related factors and the microbiota in this cohort, and estimated their effect sizes. Most variables investigated were associated with the gut microbiota. Specifically, body mass index (BMI), race, sex, and alcohol use were significantly associated with microbial beta-diversity (P < 0.05, unweighted UniFrac). BMI, race and alcohol use were also significantly associated with microbial alpha-diversity (P < 0.05, species richness). Tobacco use showed a trend toward association with the microbiota (P < 0.1, unweighted UniFrac). The effect sizes of the associations, as quantified by adjusted R(2) values based on unweighted UniFrac distances, were small (< 1% for all variables), indicating that these factors explain only a small percentage of overall microbiota variability. Nevertheless, the significant associations between these variables and the gut microbiota suggest that they could still be potential confounders in comparative studies and that controlling for these variables in study design, which is the main objective of the MWRP, is important for increasing reproducibility in comparative microbiome studies. PMID- 26839741 TI - Odd versus even: a scientific study of the 'rules' of plating. AB - We report on the results of a series of large-scale computer-based preference tests (conducted at The Science Museum in London and online) that evaluated the widely-held belief that food should be plated in odd rather than even numbers of elements in order to maximize the visual appeal of a dish. Participants were presented with pairs of plates of food showing odd versus even number of seared scallops (3 vs. 4; 1-6 in Experiment 7), arranged in a line, as a polygon or randomly, on either a round or square white plate. No consistent evidence for a preference for odd or even numbers of food items was found, thus questioning the oft-made assertion that odd number of items on a plate looks better than an even number. The implications of these results are discussed. PMID- 26839740 TI - Comparative genomics of Synechococcus and proposal of the new genus Parasynechococcus. AB - Synechococcus is among the most important contributors to global primary productivity. The genomes of several strains of this taxon have been previously sequenced in an effort to understand the physiology and ecology of these highly diverse microorganisms. Here we present a comparative study of Synechococcus genomes. For that end, we developed GenTaxo, a program written in Perl to perform genomic taxonomy based on average nucleotide identity, average amino acid identity and dinucleotide signatures, which revealed that the analyzed strains are drastically distinct regarding their genomic content. Phylogenomic reconstruction indicated a division of Synechococcus in two clades (i.e. Synechococcus and the new genus Parasynechococcus), corroborating evidences that this is in fact a polyphyletic group. By clustering protein encoding genes into homologue groups we were able to trace the Pangenome and core genome of both marine and freshwater Synechococcus and determine the genotypic traits that differentiate these lineages. PMID- 26839742 TI - Is Acropora palmata recovering? A case study in Los Roques National Park, Venezuela. AB - Eight years ago (2007), the distribution and status of Acropora palmata was quantified throughout Los Roques archipelago in Venezuela. The aim was to produce a baseline study for this species which combined population genetics with demographic data. The results highlighted that A. palmata had the potential to recover in at least 6 out of 10 sites surveyed. Recovery potential was assumed to be high at sites with a relatively high abundance of the coral, low disease prevalence, high genetic diversity, and high rates of sexual reproduction. However, as noted, Zubillaga et al. (2008) realized recovery was still strongly dependent on local and regional stressors. In 2014 (this study), the status of A. palmata was re-evaluated at Los Roques. We increased the number of sites from 10 in the original baseline study to 106. This allowed us to assess the population status throughout the entirety of the MPA. Furthermore, we also identified local threats that may have hindered population recovery. Here, we show that A. palmata now has a relatively restricted distribution throughout the park, only occurring in 15% of the sites surveyed. Large stands of old dead colonies were common throughout the archipelago; a result which demonstrates that this species has lost almost 50% of its original distribution over the past decades. The majority of corals recorded were large adults (~2 m height), suggesting that these older colonies might be less susceptible or more resilient to local and global threats. However, 45% of these surviving colonies showed evidence of partial mortality and degradation of living tissues. Interestingly, the greatest increase in partial mortality occurred at sites with the lowest levels of protection ([Formula: see text]; df = 4, p < 0.05). This may suggest there is a positive role of small scale marine management in assisting reef recovery. We also recorded a significant reduction ([Formula: see text]; df = 8; p < 0.05) in the density of A. palmata in sites that had previously been categorized as having a high potential for recovery. One explanation for this continued decline may be due to the fact that over the past 10 years, two massive bleaching events have occurred throughout the Caribbean with records showing that Los Roques has experienced unprecedented declines in overall coral cover. We therefore conclude that although local protection could promote recovery, the impacts from global threats such as ocean warming may hamper the recovery of this threatened species. PMID- 26839743 TI - L-Canavanine potentiates the cytotoxicity of doxorubicin and cisplatin in arginine deprived human cancer cells. AB - The non-protein amino acid L-canavanine (L-CAV), an antimetabolite of L-arginine (L-ARG), can alter the 3D conformation of proteins when incorporated into a protein instead of L-ARG. L-CAV inhibits the proliferation of some tumour cells. The deprivation of L-ARG in the culture medium enhances the response of cells to L-CAV. This study aimed to investigate the interaction of L-CAV in combination with the chemotherapeutic drugs, doxorubicin (DOX) or cisplatin (CIS), in cancer cells, especially in the absence of L-ARG. A combination method based on the median-effect principle and mass-action law was used. The following cancer cells were employed: HeLa and Caco-2 cells, overexpressing argininosuccinate synthase (ASS), pancreatic cells (MIA PaCa-2 and BxPC-3) and hepatocellular carcinoma cells (Hep G2 and SK-HEP-1), with down-regulated ASS. When constant and non constant ratios of L-CAV were combined with DOX and CIS, a synergistic potentiation of cytotoxicity was recorded. Cells expressing high levels of ASS were more sensitive to the treatment as compared to the cells with reduced ASS levels. Overall, this study may provide a new approach to targeting some cancer cells with L-CAV in combination with DNA-targeting drugs such as DOX and CIS, especially those cells which overexpress ASS, such as human cervical and colorectal carcinoma cells. PMID- 26839744 TI - Residual mitochondrial transmembrane potential decreases unsaturated fatty acid level in sake yeast during alcoholic fermentation. AB - Oxygen, a key nutrient in alcoholic fermentation, is rapidly depleted during this process. Several pathways of oxygen utilization have been reported in the yeast Saccharomyces cerevisiae during alcoholic fermentation, namely synthesis of unsaturated fatty acid, sterols and heme, and the mitochondrial electron transport chain. However, the interaction between these pathways has not been investigated. In this study, we showed that the major proportion of unsaturated fatty acids of ester-linked lipids in sake fermentation mash is derived from the sake yeast rather than from rice or koji (rice fermented with Aspergillus). Additionally, during alcoholic fermentation, inhibition of the residual mitochondrial activity of sake yeast increases the levels of unsaturated fatty acids of ester-linked lipids. These findings indicate that the residual activity of the mitochondrial electron transport chain reduces molecular oxygen levels and decreases the synthesis of unsaturated fatty acids, thereby increasing the synthesis of estery flavors by sake yeast. This is the first report of a novel link between residual mitochondrial transmembrane potential and the synthesis of unsaturated fatty acids by the brewery yeast during alcoholic fermentation. PMID- 26839745 TI - One-step multiplex real-time RT-PCR assay for detecting and genotyping wild-type group A rotavirus strains and vaccine strains (Rotarix(r) and RotaTeq(r)) in stool samples. AB - Background. Group A rotavirus (RVA) infection is the major cause of acute gastroenteritis (AGE) in young children worldwide. Introduction of two live attenuated rotavirus vaccines, RotaTeq(r) and Rotarix(r), has dramatically reduced RVA associated AGE and mortality in developed as well as in many developing countries. High-throughput methods are needed to genotype rotavirus wild-type strains and to identify vaccine strains in stool samples. Quantitative RT-PCR assays (qRT-PCR) offer several advantages including increased sensitivity, higher throughput, and faster turnaround time. Methods. In this study, a one-step multiplex qRT-PCR assay was developed to detect and genotype wild-type strains and vaccine (Rotarix(r) and RotaTeq(r)) rotavirus strains along with an internal processing control (Xeno or MS2 RNA). Real-time RT-PCR assays were designed for VP7 (G1, G2, G3, G4, G9, G12) and VP4 (P[4], P[6] and P[8]) genotypes. The multiplex qRT-PCR assay also included previously published NSP3 qRT-PCR for rotavirus detection and Rotarix(r) NSP2 and RotaTeq(r) VP6 qRT-PCRs for detection of Rotarix(r) and RotaTeq(r) vaccine strains respectively. The multiplex qRT-PCR assay was validated using 853 sequence confirmed stool samples and 24 lab cultured strains of different rotavirus genotypes. By using thermostable rTth polymerase enzyme, dsRNA denaturation, reverse transcription (RT) and amplification (PCR) steps were performed in single tube by uninterrupted thermocycling profile to reduce chances of sample cross contamination and for rapid generation of results. For quantification, standard curves were generated using dsRNA transcripts derived from RVA gene segments. Results. The VP7 qRT-PCRs exhibited 98.8-100% sensitivity, 99.7-100% specificity, 85-95% efficiency and a limit of detection of 4-60 copies per singleplex reaction. The VP7 qRT-PCRs exhibited 81-92% efficiency and limit of detection of 150-600 copies in multiplex reactions. The VP4 qRT-PCRs exhibited 98.8-100% sensitivity, 100% specificity, 86 89% efficiency and a limit of detection of 12-400 copies per singleplex reactions. The VP4 qRT-PCRs exhibited 82-90% efficiency and limit of detection of 120-4000 copies in multiplex reaction. Discussion. The one-step multiplex qRT-PCR assay will facilitate high-throughput rotavirus genotype characterization for monitoring circulating rotavirus wild-type strains causing rotavirus infections, determining the frequency of Rotarix(r) and RotaTeq(r) vaccine strains and vaccine-derived reassortants associated with AGE, and help to identify novel rotavirus strains derived by reassortment between vaccine and wild-type strains. PMID- 26839746 TI - Faces in commonly experienced configurations enter awareness faster due to their curvature relative to fixation. AB - The extent to which perceptually suppressed face stimuli are still processed has been extensively studied using the continuous flash suppression paradigm (CFS). Studies that rely on breaking CFS (b-CFS), in which the time it takes for an initially suppressed stimulus to become detectable is measured, have provided evidence for relatively complex processing of invisible face stimuli. In contrast, adaptation and neuroimaging studies have shown that perceptually suppressed faces are only processed for a limited set of features, such as its general shape. In this study, we asked whether perceptually suppressed face stimuli presented in their commonly experienced configuration would break suppression faster than when presented in an uncommonly experienced configuration. This study was motivated by a recent neuroimaging study showing that commonly experienced face configurations are more strongly represented in the fusiform face area. Our findings revealed that faces presented in commonly experienced configurations indeed broke suppression faster, yet this effect did not interact with face inversion suggesting that, in a b-CFS context, perceptually suppressed faces are potentially not processed by specialized (high level) face processing mechanisms. Rather, our pattern of results is consistent with an interpretation based on the processing of more basic visual properties such as convexity. PMID- 26839748 TI - Trophic ecology of sea urchins in coral-rocky reef systems, Ecuador. AB - Sea urchins are important grazers and influence reef development in the Eastern Tropical Pacific (ETP). Diadema mexicanum and Eucidaris thouarsii are the most important sea urchins on the Ecuadorian coastal reefs. This study provided a trophic scenario for these two species of echinoids in the coral-rocky reef bottoms of the Ecuadorian coast, using stable isotopes. We evaluated the relative proportion of algal resources assimilated, and trophic niche of the two sea urchins in the most southern coral-rocky reefs of the ETP in two sites with different disturbance level. Bayesian models were used to estimate the contribution of algal sources, niche breadth, and trophic overlap between the two species. The sea urchins behaved as opportunistic feeders, although they showed differential resource assimilation. Eucidaris thouarsii is the dominant species in disturbed environments; likewise, their niche amplitude was broader than that of D. mexicanum when conditions were not optimal. However, there was no niche overlap between the species. The Stable Isotope Analysis in R (SIAR) indicated that both sea urchins shared limiting resources in the disturbed area, mainly Dictyota spp. (contributions of up to 85% for D. mexicanum and up to 75% for E. thouarsii). The Stable Isotope Bayesian Ellipses in R (SIBER) analysis results indicated less interspecific competition in the undisturbed site. Our results suggested a trophic niche partitioning between sympatric sea urchin species in coastal areas of the ETP, but the limitation of resources could lead to trophic overlap and stronger habitat degradation. PMID- 26839747 TI - Evaluation of the global impacts of mitigation on persistent, bioaccumulative and toxic pollutants in marine fish. AB - Although persistent, bioaccumulative and toxic pollutants (PBTs) are well-studied individually, their distribution and variability on a global scale are largely unknown, particularly in marine fish. Using 2,662 measurements collected from peer-reviewed literature spanning 1969-2012, we examined variability of five classes of PBTs, considering effects of geography, habitat, and trophic level on observed concentrations. While we see large-scale spatial patterning in some PBTs (chlordanes, polychlorinated biphenyls), habitat type and trophic level did not contribute to significant patterning, with the exception of mercury. We further examined patterns of change in PBT concentration as a function of sampling year. All PBTs showed significant declines in concentration levels through time, ranging from 15-30% reduction per decade across PBT groups. Despite consistent evidence of reductions, variation in pollutant concentration remains high, indicating ongoing consumer risk of exposure to fish with pollutant levels exceeding EPA screening values. The temporal trends indicate that mitigation programs are effective, but that global levels decline slowly. In order for monitoring efforts to provide more targeted assessments of risk to PBT exposure, these data highlight an urgent need for improved replication and standardization of pollutant monitoring protocols for marine finfish. PMID- 26839749 TI - Cranial ontogenetic variation in early saurischians and the role of heterochrony in the diversification of predatory dinosaurs. AB - Non-avian saurischian skulls underwent at least 165 million years of evolution and shapes varied from elongated skulls, such as in the theropod Coelophysis, to short and box-shaped skulls, such as in the sauropod Camarasaurus. A number of factors have long been considered to drive skull shape, including phylogeny, dietary preferences and functional constraints. However, heterochrony is increasingly being recognized as an important factor in dinosaur evolution. In order to quantitatively analyse the impact of heterochrony on saurischian skull shape, we analysed five ontogenetic trajectories using two-dimensional geometric morphometrics in a phylogenetic framework. This allowed for the comparative investigation of main ontogenetic shape changes and the evaluation of how heterochrony affected skull shape through both ontogenetic and phylogenetic trajectories. Using principal component analyses and multivariate regressions, it was possible to quantify different ontogenetic trajectories and evaluate them for evidence of heterochronic events allowing testing of previous hypotheses on cranial heterochrony in saurischians. We found that the skull shape of the hypothetical ancestor of Saurischia likely led to basal Sauropodomorpha through paedomorphosis, and to basal Theropoda mainly through peramorphosis. Paedomorphosis then led from Orionides to Avetheropoda, indicating that the paedomorphic trend found by previous authors in advanced coelurosaurs may extend back into the early evolution of Avetheropoda. Not only are changes in saurischian skull shape complex due to the large number of factors that affected it, but heterochrony itself is complex, with a number of possible reversals throughout non-avian saurischian evolution. In general, the sampling of complete ontogenetic trajectories including early juveniles is considerably lower than the sampling of single adult or subadult individuals, which is a major impediment to the study of heterochrony on non-avian dinosaurs. Thus, the current work represents an exploratory analysis. To better understand the cranial ontogeny and the impact of heterochrony on skull evolution in saurischians, the data set that we present here must be expanded and complemented with further sampling from future fossil discoveries, especially of juvenile individuals. PMID- 26839751 TI - Bust economics: foragers choose high quality habitats in lean times. AB - In environments where food resources are spatially variable and temporarily impoverished, consumers that encounter habitat patches with different food density should focus their foraging initially where food density is highest before they move to patches where food density is lower. Increasing missed opportunity costs should drive individuals progressively to patches with lower food density as resources in the initially high food density patches deplete. To test these expectations, we assessed the foraging decisions of two species of dasyurid marsupials (dunnarts: Sminthopsis hirtipes and S. youngsoni) during a deep drought, or bust period, in the Simpson Desert of central Australia. Dunnarts were allowed access to three patches containing different food densities using an interview chamber experiment. Both species exhibited clear preference for the high density over the lower food density patches as measured in total harvested resources. Similarly, when measuring the proportion of resources harvested within the patches, we observed a marginal preference for patches with initially high densities. Models analyzing behavioral choices at the population level found no differences in behavior between the two species, but models analyzing choices at the individual level uncovered some variation. We conclude that dunnarts can distinguish between habitat patches with different densities of food and preferentially exploit the most valuable. As our observations were made during bust conditions, experiments should be repeated during boom times to assess the foraging economics of dunnarts when environmental resources are high. PMID- 26839750 TI - Non-invasive cortisol measurements as indicators of physiological stress responses in guinea pigs. AB - Non-invasive measurements of glucocorticoid (GC) concentrations, including cortisol and corticosterone, serve as reliable indicators of adrenocortical activities and physiological stress loads in a variety of species. As an alternative to invasive analyses based on plasma, GC concentrations in saliva still represent single-point-of-time measurements, suitable for studying short term or acute stress responses, whereas fecal GC metabolites (FGMs) reflect overall stress loads and stress responses after a species-specific time frame in the long-term. In our study species, the domestic guinea pig, GC measurements are commonly used to indicate stress responses to different environmental conditions, but the biological relevance of non-invasive measurements is widely unknown. We therefore established an experimental protocol based on the animals' natural stress responses to different environmental conditions and compared GC levels in plasma, saliva, and fecal samples during non-stressful social isolations and stressful two-hour social confrontations with unfamiliar individuals. Plasma and saliva cortisol concentrations were significantly increased directly after the social confrontations, and plasma and saliva cortisol levels were strongly correlated. This demonstrates a high biological relevance of GC measurements in saliva. FGM levels measured 20 h afterwards, representing the reported mean gut passage time based on physiological validations, revealed that the overall stress load was not affected by the confrontations, but also no relations to plasma cortisol levels were detected. We therefore measured FGMs in two-hour intervals for 24 h after another social confrontation and detected significantly increased levels after four to twelve hours, reaching peak concentrations already after six hours. Our findings confirm that non-invasive GC measurements in guinea pigs are highly biologically relevant in indicating physiological stress responses compared to circulating levels in plasma in the short- and long-term. Our approach also underlines the importance of detailed investigations on how to use and interpret non-invasive measurements, including the determination of appropriate time points for sample collections. PMID- 26839752 TI - Protective effects of the extracts of Barringtonia racemosa shoots against oxidative damage in HepG2 cells. AB - Barringtonia racemosa is a tropical plant with medicinal values. In this study, the ability of the water extracts of the leaf (BLE) and stem (BSE) from the shoots to protect HepG2 cells against oxidative damage was studied. Five major polyphenolic compounds consisting of gallic acid, ellagic acid, protocatechuic acid, quercetin and kaempferol were identified using HPLC-DAD and ESI-MS. Cell viability assay revealed that BLE and BSE were non-cytotoxic (cell viabilities >80%) at concentration less than 250 ug/ml and 500 ug/ml, respectively. BLE and BSE improved cellular antioxidant status measured by FRAP assay and protected HepG2 cells against H2O2-induced cytotoxicity. The extracts also inhibited lipid peroxidation in HepG2 cells as well as the production of reactive oxygen species. BLE and BSE could also suppress the activities of superoxide dismutase and catalase during oxidative stress. The shoots of B. racemosa can be an alternative bioactive ingredient in the prevention of oxidative damage. PMID- 26839753 TI - Microfluidic Chip Coupled with Thermal Desorption Atmospheric Pressure Ionization Mass Spectrometry. AB - Microfluidic chips have been used as platforms for a diversity of research purposes such as for separation and micro-reaction. One of the suitable detectors for microfluidic chip is mass spectrometry. Because microfluidic chips are generally operated in an open air condition, mass spectrometry coupled with atmospheric pressure ion sources can suit the requirement with minimum compromise. In this study, we develop a new interface to couple a microfluidic chip with mass spectrometry. A capillary tip coated with a layer of graphite, capable of absorbing energy of near-infrared (NIR) light is used to interface microfluidic chip with mass spectrometry. An NIR laser diode (lambda=808 nm) is used to irradiate the capillary tip for assisting the generation of spray from the eluent of the microfluidic chip. An electrospray is provided to fuse with the spray generated from the microfluidic chip for post-ionization. Transesterification is used as the example to demonstrate the feasibility of using this interface to couple microfluidic chip with mass spectrometry. PMID- 26839754 TI - Impact of systemic risk in the real estate sector on banking return. AB - In this paper, we measure systemic risk in the real estate sector based on contingent claims analysis, and then investigate its impact on banking return. Based on the data in China, we find that systemic risk in the real estate sector has a negative effect on banking return, but this effect is temporary; banking risk aversion and implicit interest expense have considerable impact on banking return. PMID- 26839755 TI - Analysis of bus passenger comfort perception based on passenger load factor and in-vehicle time. AB - Although bus comfort is a crucial indicator of service quality, existing studies tend to focus on passenger load and ignore in-vehicle time, which can also affect passengers' comfort perception. Therefore, by conducting surveys, this study examines passengers' comfort perception while accounting for both factors. Then, using the survey data, it performs a two-way analysis of variance and shows that both in-vehicle time and passenger load significantly affect passenger comfort. Then, a bus comfort model is proposed to evaluate comfort level, followed by a sensitivity analysis. The method introduced in this study has theoretical implications for bus operators attempting to improve bus service quality. PMID- 26839756 TI - Use of body linear measurements to estimate liveweight of crossbred dairy cattle in smallholder farms in Kenya. AB - Body linear measurements, and specifically heart girth (HG), have been shown to be useful predictors of cattle liveweight. To test the accuracy of body linear measurements for predicting liveweight, crossbred dairy cattle of different genotypes were measured and weighed. A total of 352 mature cows and 100 heifers were weighed using an electronic weighing scale and measurements of HG, body length, height at withers were taken using an ordinary measuring tape and body condition scored (BCS) using a five-point scale. The animals were grouped according to genotype and age. Genotype classification was undertaken from farmer recall and by visual appraisal as 40-60, 61-80 or 81-100 % exotic (non indigenous). Age classification was simply as mature cows or heifers. Liveweight of the animals ranged from 102 to 433 kg. Liveweight was strongly correlated with HG (r = 0.84) and body condition scores (r = 0.70) and moderately correlated with body length (r = 0.64) and height at withers (0.61). Regressing LW on HG measurements gave statistically significant (P < 0.01) equations with R(2) ranging from of 0.53 to 0.78 and residual standard deviation ranging from 18.11 to 40.50 kg. The overall model developed (adjusted R(2) = 0.71) had a prediction error of 26 kg (or 11 % of the mean) and predicted LW of over 95 % of crossbred dairy cattle in the range of 100-450 kg, regardless of age and breed group. Including BCS in the model slightly improved the model fit but not the prediction error. It was concluded that the model can be useful in making general management decisions in smallholder farms. PMID- 26839757 TI - Application of discrete wavelet transform for analysis of genomic sequences of Mycobacterium tuberculosis. AB - This paper highlights the potential of discrete wavelet transforms in the analysis and comparison of genomic sequences of Mycobacterium tuberculosis (MTB) with different resistance characteristics. Graphical representations of wavelet coefficients and statistical estimates of their parameters have been used to determine the extent of similarity between different sequences of MTB without the use of conventional methods such as Basic Local Alignment Search Tool. Based on the calculation of the energy of wavelet decomposition coefficients of complete genomic sequences, their broad classification of the type of resistance can be done. All the given genomic sequences can be grouped into two broad categories wherein the drug resistant and drug susceptible sequences form one group while the multidrug resistant and extensive drug resistant sequences form the other group. This method of segregation of the sequences is faster than conventional laboratory methods which require 3-4 weeks of culture of sputum samples. Thus the proposed method can be used as a tool to enhance clinical diagnostic investigations in near real-time. PMID- 26839759 TI - Epidemic model for information diffusion in web forums: experiments in marketing exchange and political dialog. AB - As social media has become more prevalent, its influence on business, politics, and society has become significant. Due to easy access and interaction between large numbers of users, information diffuses in an epidemic style on the web. Understanding the mechanisms of information diffusion through these new publication methods is important for political and marketing purposes. Among social media, web forums, where people in online communities disseminate and receive information, provide a good environment for examining information diffusion. In this paper, we model topic diffusion in web forums using the epidemiology model, the susceptible-infected-recovered (SIR) model, frequently used in previous research to analyze both disease outbreaks and knowledge diffusion. The model was evaluated on a large longitudinal dataset from the web forum of a major retail company and from a general political discussion forum. The fitting results showed that the SIR model is a plausible model to describe the diffusion process of a topic. This research shows that epidemic models can expand their application areas to topic discussion on the web, particularly social media such as web forums. PMID- 26839758 TI - Need of cost-effective vaccines in developing countries: What plant biotechnology can offer? AB - To treat current infectious diseases, different therapies are used that include drugs or vaccines or both. Currently, the world is facing an increasing problem of drug resistance from many pathogenic microorganisms. In majority of cases, when vaccines are used, formulations consist of live attenuated microorganisms. This poses an additional risk of infection in immunocompromised patients and people suffering from malnutrition in developing countries. Therefore, there is need to improve drug therapy as well as to develop next generation vaccines, in particular against infectious diseases with highest mortality rates. For patients in developing countries, costs related to treatments are one of the major hurdles to reduce the disease burden. In many cases, use of prophylactic vaccines can help to control the incidence of infectious diseases. In the present review, we describe some infectious diseases with high impact on health of people in low and middle income countries. We discuss the prospects of plants as alternative platform for the development of next-generation subunit vaccines that can be a cost-effective source for mass immunization of people in developing countries. PMID- 26839760 TI - Downstream assessment of chlorinated organic compounds in the bed-sediment of Aiba Stream, Iwo, South-Western, Nigeria. AB - This study investigated levels and distribution pattern of chlorinated organic compounds (COCs) otherwise known as organochlorine pesticides in sediment samples at downstream of Aiba watercourse in Iwo, South-western Nigeria. Soxhlet extraction method followed by GC-ECD analysis were used to ascertain levels of COCs in the sediment samples collected from four different locations along the stream. Eighteen COCs were detected with trans permethrin and endosulfan sulfate having highest and lowest concentrations of 375.70 +/- 689.41 and 0.03 +/- 0.05 ug/g, respectively. The varying levels of COCs as obtained in this study were attributed to organochlorine pesticides contamination emanated from different agricultural practices and domestic sewage loads of the study area. PMID- 26839762 TI - Morphological characterization of breeds of sheep: a discriminant analysis approach. AB - In this study the characterisation and separation/discrimination of three sheep breeds (crosses, West African Dwarfs (WAD) and West African Long Legged (WALL)] based on their physical traits (morphological characterisation) was investigated extensively with the application of discriminant analysis. The study's main objective was specifically based on developing a variable selection criterion that can discriminate best among the three sheep breeds and as well as obtain a reliable mathematical function/equation (discriminant functions) for provision of maximum separation among the three known sheep breeds. Data from College of Education, Mampong animal farms on various breeds of sheep (hybrid/crossed breed, Sahell/WALL and Djallonke/WAD) was used. Factor Analysis was employed as a variable selection criterion for selecting six sheep traits that can discriminate best among the sheep breeds. Canonical discriminant function was derived for the eight variable data set and was compared with the derived quadratic discriminant functions (QDFs) using the six extracted sheep traits. The six variable QDF distance classifier provided maximum separation after cross validation than the 8 variable canonical discriminant functions. The derived mathematical functions (QDFs) were able to provide maximum separation among the three known sheep breeds with a correct classification rate of 0.86. PMID- 26839761 TI - Selective salvage of zones 2 and 4 in the pedicled TRAM flap: a focus on reducing fat necrosis and improving aesthetic outcomes. AB - The introduction of microsurgery has decreased the frequency of using the pedicled transverse rectus abdominis musculocutaneous (TRAM) flap, owing to its higher incidence of fat necrosis and limitations in flap insetting (vs. the free TRAM flap). We devised an efficient method of using zones 2 and 4, based on the pedicled flap's vascular anatomy, to reduce fat necrosis and achieve superior aesthetic outcomes during immediate breast reconstruction using the pedicled TRAM flap. Between April 2011 and February 2015, we performed immediate breast reconstruction using the contralateral unipedicled TRAM flap for 136 breast cancer patients. The conventional method (insetting by removing zone 4 and part of zone 2) was used for 83 patients (Group A), and selective salvage of zones 2 and 4 (our proposed method) was used for 53 patients (Group B). Fat necrosis was observed in 17 patients (20.48 %) and 4 patients (7.55 %) from Groups A and B, respectively (p = 0.033). The average patient satisfaction scores at 6 months (comparing the reconstructed and contralateral breasts) were 7.01 and 8.02 in Groups A and B, respectively (p < 0.001). Liposuction to improve the upper-pole contour was performed at 6 months for 13 patients in Group A, although no patients in Group B required a secondary procedure (p = 0.002). Fat necrosis can be reduced via selective salvage of zones 2 and 4, based on the pedicled TRAM flap's vascular anatomy. Furthermore, superior aesthetic outcomes can be achieved via flap insetting using the three-dimensional concept. Level of evidence Procedure comparison, Level II. PMID- 26839763 TI - Is in-group bias culture-dependent? A meta-analysis across 18 societies. AB - We report a meta-analysis on the relationship between in-group bias and culture. Our focus is on whether broad macro-contextual variables influence the extent to which individuals favour their in-group. Data from 21,266 participants from 18 societies included in experimental and survey studies were available. Using Hofstede's (1980) and Schwartz (2006) culture-level predictors in a 3-level mixed effects meta-analysis, we found strong support for the uncertainty-reduction hypothesis. An interaction between Autonomy and real vs artificial groups suggested that in low autonomy contexts, individuals show greater in-group bias for real groups. Implications for social identity theory and intergroup conflict are outlined. PMID- 26839764 TI - Deletion of exon 8 from the EXT1 gene causes multiple osteochondromas (MO) in a family with three affected members. AB - Multiple osteochondromas (also called hereditary multiple exostoses) is an autosomal dominant disorder characterized by multiple cartilaginous tumors, which are caused by mutations in the genes for exostosin-1 (EXT1) and exostosin-2 (EXT2). The goal of this study was to elucidate the genetic alterations in a family with three affected members. Isolation of RNA from the patients' blood followed by reverse transcription and PCR amplification of selected fragments showed that the three patients lack a specific region of 90 bp from their EXT1 mRNA. This region corresponds to the sequence of exon 8 from the EXT1 gene. No splice site mutation was found around exon 8. However, long-range PCR amplification of the region from intron 7 to intron 8 indicated that the three patients contain a deletion of 4318 bp, which includes exon 8 and part of the flanking introns. There is evidence that the deletion was caused by non homologous end joining because the breakpoints are not located within a repetitive element, but contain multiple copies of the deletion hotspot sequence TGRRKM. Exon 8 encodes part of the active site of the EXT1 enzyme, including the DXD signature of all UDP-sugar glycosyltransferases. It is conceivable that the mutant protein exerts a dominant negative effect on the activity of the EXT glycosyltransferase since it might interact with normal copies of the enzyme to form an inactive hetero-oligomeric complex. We suggest that sequencing of RNA might be superior to exome sequencing to detect short deletions of a single exon. PMID- 26839765 TI - Metabolic responses of eukaryotic microalgae to environmental stress limit the ability of FT-IR spectroscopy for species identification. AB - Fourier Transform Infrared (FT-IR) spectroscopy is a robust method for macromolecular analysis and differentiation of microorganisms. However, most studies are performed in controlled conditions and it is unclear whether this tool is appropriate for the identification of eukaryotic microalgae species from variable environments. In order to address this, nine closely-related species of marine and freshwater microalgae were grown under controlled (non-stressed) and variable (non-stressed and stressed) conditions, including nutrient-stressed and wastewater-stressed conditions. Following optimization of data processing methods, FT-IR spectra from all species and conditions were compared. The substantial metabolic changes that were caused by nutrient starvation restricted the ability of FT-IR spectroscopy to differentiate the microalgal species grown under variable conditions efficiently. Comparison of unsupervised and supervised multivariate data analysis methods found that principal component-discriminant function analysis was able best to differentiate between some species under controlled conditions but still gave poor differentiation under variable environmental conditions. PMID- 26839766 TI - Allergic bronchopulmonary mycosis due to co-infection with Aspergillus fumigatus and Schizophyllum commune. AB - A 61-year-old female presented with eosinophilic pneumonia accompanied by bronchial asthma. She was finally diagnosed with allergic bronchopulmonary mycosis (ABPM) due to co-infection with Aspergillus fumigatus and Schizophyllum commune detected by genetic analysis of the plug and from cultures. PMID- 26839767 TI - Pruritis and palpable purpura from leeches in the Australian Rainforest. AB - Leeches are prevalent in the Australian Rainforest. We report two cases of leech bites resulting in pruritis and palpable purpura. The dermatologic sequelae of leech bites, differential diagnosis of pruritic palpable purpura, leech bite treatment, prevention, and complications are reviewed. PMID- 26839768 TI - Hyperimmunoglobulin E syndrome with persistent vertebral osteomyelitis due to methicillin-resistant Staphylococcus aureus: Case report and review of the literature. AB - We report a case of vertebral osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA) with a slowly progressive, relatively asymptomatic course in a young woman with suspected hyperimmunoglobulin E syndrome (Job's syndrome). PMID- 26839769 TI - Neonatal herpes simplex virus presenting with isolated liver failure. AB - Disseminated neonatal herpes simplex virus infection usually presents with multi organ involvement. Untreated, this disease has a mortality rate of approximately 80%. Here, we describe a well-appearing 3-week old infant with isolated compensated hepatic failure caused by HSV-2. PMID- 26839770 TI - Management of serology negative human hepatic hydatidosis (caused by Echinococcus granulosus) in a young woman from Bangladesh in a resource-rich setting: A case report. AB - Human cystic echinococcosis (hydatidosis) is a parasitic zoonosis with almost complete worldwide distribution. Echinococcus granulosus, the dog tapeworm, causes hydatidosis which accounts for 95% of human echinococcosis. Although this tapeworm is found in dogs as a definitive host and a number of intermediate hosts, humans are often infected from close contact with infected dogs. Humans are not part of the parasitic lifecycle and serve as accidental hosts. Hydatidosis is an important consideration in the differential diagnosis of hepatic cysts in individuals from endemic areas. Clinicians should be aware of the long incubation period, the high frequency of negative serological tests, and the possibility of intraoperative evaluations of the cyst aspirate being non diagnostic. We describe a case of serology negative hydatidosis that came to medical attention as an incidental finding in a young woman from Bangladesh. The patient underwent imaging and was then started on albendazole. After several weeks of albendazole, the cyst was punctured, aspirated, injected with hypertonic saline, re-aspirated, and then fully excised. Diagnosis was confirmed by microscopic evaluation of the cyst aspirate. Serological tests for hydatidosis may be negative in patients with early disease and thus should not be used to rule out this disease. Consideration of this diagnosis allows clinicians to avoid the catastrophic spillage of cystic contents risking an anaphylactic reaction, which might prove fatal. Despite World Health Organization hydatidosis staging being based on ultrasound, radiologists in resource-rich setting may prefer MRI in the management and staging of cystic echinococcosis. PMID- 26839771 TI - Mycobacterium avium complex enteritis in HIV-infected patient. AB - Disseminated Mycobacterium avium complex (MAC) infection is an important AIDS defining opportunistic infection. The introduction of antimicrobial prophylaxis and antiretroviral therapy (ART) markedly reduced the incidence of disseminated MAC infection and improved the survival of affected individuals. However, it seems that patients with new or recurrent MAC infection are still encountered in clinical practice. Our images captured the characteristic endoscopic findings of MAC duodenitis. The gastrointestinal (GI) tract appears to be a common port of entry for MAC infection in patients with AIDS. Early recognition of GI MAC infection by endoscopy in HIV-infected patients and initiation of anti-MAC therapy and ART may reduce morbidity and mortality. PMID- 26839772 TI - Traveler's encounter with nymphs in a hotel bed. AB - This case illustrates skin lesions in a traveler staying in a hotel bed infested with tics. Although infestation of hotels with bedbugs belonging to the Cimex genus is a growing problem worldwide, tick infestation has never been reported before. PMID- 26839774 TI - Spontaneous splenic rupture due to Babesia microti infection: Case report and review of the literature. AB - This article describes the case of spontaneous splenic rupture as a rare complication of infection with Babesia species. We will discuss the symptomatology that this disease could present along with both surgical and non surgical management approaches. Babesia infection often presents with mild to moderate symptoms, but can rapidly progress to significant injury including splenic rupture. The first case reported in a medical journal was in 2007. Treatment usually involves a two-drug regimen; clindamycin plus quinine, or atovaquone plus azithromycin (as in our patient). If hemodynamic stability is present, a primary non-surgical treatment may be especially beneficial since splenectomy may worsen optimal immunologic function and the infection itself. PMID- 26839773 TI - A depiction of imported malaria in Connecticut. AB - In 2010, there were roughly 219 million cases of malaria reported worldwide resulting in an estimated 660,600 deaths [1]. In contrast, the total number of cases according to the Centers for Disease Control and Prevention (CDC) in the United States (USA) was only 1691 [2]. Of those, 1688 were cases of imported malaria [2]. This is the highest number of cases reported in U.S. since 1980 [2]. Here, we describe a case of imported malaria and conduct a retrospective case series at four Connecticut (CT) hospitals in order to describe the demographics of imported malaria and to identify potential barriers to timely diagnosis and treatment. PMID- 26839775 TI - Anti-NMDAR encephalitis, a mimicker of acute infectious encephalitis and a review of the literature. AB - Anti-N-methyl-d-aspartate receptor encephalitis has become an increasingly recognized etiology of acute psychosis in young patients. The diverse constellation of symptoms allows for misdiagnosis as an infectious, psychological, or toxicological entity resulting in delays in treatment with increasing morbidity. We describe a case of anti-NMDAR encephalitis that was a particular challenge to diagnose. Practitioners should maintain a high index of suspicion for anti-NMDAR and related neuroautoimmune syndromes, especially in young patients that present with acute mental status decline or dyskinesia. PMID- 26839776 TI - Disseminated cutaneous infection due to Mycobacterium chelonae following hematopoietic stem cell transplantation. AB - This report describes two cases of disseminated cutaneous Mycobacterium chelonae after hematopoietic stem cell transplantation (HSCT). PMID- 26839777 TI - Pseudomonas bacteremia as an initial presentation of SLE. AB - Infections have been commonly implicated in lupus relapses and in some cases as initiating the diagnostic work up of systemic lupus erythematosus (SLE). We describe here the case of a young patient who presented with Pseudomonas aeruginosa bacteremia and was found to have a new diagnosis of SLE. 53% of patients with active SLE and abdominal pain have intestinal vasculitis. These vasculitic changes can cause intestinal ischemia with consequent translocation of pathogens from the gastrointestinal tract to the bloodstream causing sepsis. PMID- 26839778 TI - Disseminated mycobacterium tuberculosis: Pulmonary and musculoskeletal infections in a previously healthy man. AB - Chest wall masses are an uncommon result of Mycobacterium tuberculosis (MTB) infection especially in immune-competent patients. Herein, we report a case of 47 year-old previously healthy man who presented with an anterior chest wall mass, along with a swelling of the left fourth finger. MTB was recovered from the patient's sputum and from the aspirate of the chest wall mass. Four anti tuberculous drugs for 2 months then 2 drugs for 7 months resulted in complete resolution of both masses with no need for surgical resection. CONCLUSION: MTB can present in disseminated form in a healthy man and treated with quadruple anti tuberculous medications without surgical intervention. PMID- 26839779 TI - Central nervous system infections masquerading as cerebrovascular accidents: Case series and review of literature. AB - INTRODUCTION: Central nervous system (CNS) infections can have various presentations including Cerebrovascular accidents (CVA) which may go unrecognized as a presentation of infection. We describe three cases of different CNS infections complicated by CVA. PRESENTATION: Case 1 describes a 27-year-old man, presenting with symptoms consistent with a transient ischemic attack found to have racemose neurocysticercosis. Case 2 describes a 55-year-old man with low grade fevers for 4 weeks accompanied by visual and gait disturbances and delayed speech diagnosed with multiple small left thalamocapsular and superior cerebellar infarcts secondary to cryptococcal meningitis. The third case describes a man with pneumococcal meningitis complicated by cerebellar infarcts. DISCUSSION: CNS vascular compromise secondary to infections may be due to vasculitis, an immune mediated parainfectious process causing vasospasm or thrombosis, or a hypercoagulable state with endothelial dysfunction. Patients with CVAs are at risk for aspiration pneumonia, urinary tract infections (especially catheter related) and other nosocomial infections and their clinical presentation may be very similar to CNS infections. CONCLUSION: The cases described demonstrate that CNS infections need to be considered in the differential diagnosis of CVAs presenting with fevers. The signs and symptoms of non-CNS infections associated with CVAs may be clinically indistinguishable from those of CNS infections. The outcomes of untreated CNS infections are extremely poor. It is thus imperative to have a high index of suspicion for CNS infection when evaluating CVAs with fevers or other signs of infection. PMID- 26839780 TI - Pulmonary Kaposi's sarcoma as the initial presentation of human immunodeficiency virus infection. AB - Kaposi's sarcoma (KS) usually presents in HIV-infected patients with cutaneous lesions that may advance to extensive visceral disease. There have been only a few documented cases in which the initial presentation of Kaposi's sarcoma involved the bronchopulmonary system. We describe a newly diagnosed patient who presented with pulmonary KS as his initial presentation of the disease. Our report is intended to increase clinicians' awareness that pulmonary Kaposi's sarcoma should be considered in HIV-infected patients who present with respiratory symptoms, even if they do not manifest the typical mucocutaneous manifestations of KS or have low CD4 counts. Early diagnosis and therapy are essential in improving outcomes as this condition carries a high mortality. PMID- 26839781 TI - Malarial retinopathy affecting visual function in a Malawian adult with cerebral malaria. PMID- 26839782 TI - Phaeoacremonium parasiticum phaeohyphomycosis in a patient with systemic lupus erythematosus treated successfully with surgical debridement and voriconazole: A case report and review of the literature. AB - A 26-year old woman presented for evaluation of extensive edema, erythema, sinus tract formation and purulent drainage from the left lower extremity after trauma from a wooden object approximately three months prior. Skin biopsies and blood cultures revealed Phaeoacremonium parasiticum consistent with a diagnosis of phaeohyphomycosis. Despite hospitalization and initial treatment with several antifungals, including voriconazole, her infection progressed. Surgical debridement with split thickness skin grafting was performed. Subsequent clinical improvement allowed a transition from intravenous to oral voriconazole and discharge home. Seven months post presentation she remained on oral voriconazole with significant improvement and no clinical evidence of recurrence. This case illustrates an approach to management where aggressive debridement with split thickness skin grafting and a prolonged course of intravenous and oral antifungals resulted in a good long-term outcome for the patient. PMID- 26839783 TI - Facial ulcerations due to Acinetobacter baumannii: Vessel thrombosis with bacterial mycelia. AB - A 14-year-old girl presented with a 2-week history of progressive facial ulcerations that did not respond to cephalexin and topical dexamethasone. Biopsy on the ulcer showed rod-shaped bacteria and actinomycetes-like mycelia in the vessel walls and within thrombi. Tissue culture yielded Acinetobacter baumannii, which was resistant to cephalexin. A favourite outcome was achieved with minocycline treatment. This is the first case report of A. baumannii-related vasculitis. PMID- 26839784 TI - Typical and unusual cases of female genital tuberculosis. AB - Tuberculosis is a disease with myriad presentations and manifestations; it can affect any organ or tissue, excluding only hair and nails. Doctors who are not familiar with extrapulmonary tuberculosis often overlook this disease. Urogenital tuberculosis (UGTB) is the second most common form of TB in countries with severe epidemic situation and the third most common form in regions with low incidence of TB. The term "Urogenital tuberculosis" includes kidney tuberculosis; male and female tuberculosis and urinary tract tuberculosis as complication of kidney tuberculosis. We describe rarest case of tuberculosis of a placenta in young woman, suffered from genital tuberculosis, which was overlooked before delivery, as well as typical tubo-ovarian tuberculomas. PMID- 26839785 TI - Trouble in paradise. PMID- 26839786 TI - Extrapulmonary tuberculosis presenting as a cavernous sinus syndrome: Case report with review of existing literature. AB - Tuberculoma involving the cavernous sinus is a rare presentation of CNS disease, with only twelve cases reported in previous literature. We report a case of a 48 year old woman who presented with a right cavernous sinus syndrome of 2 months duration. MRI showed a mass in the right cavernous sinus, and serologic workup revealed an elevated sedimentation rate and positive Quantiferon((r))-GOLD testing. 18-FDG PET-CT demonstrated a hypermetabolic 3 cm subcarinal lymph node, and lymph node biopsy showed caseating granuloma. Culture of lymphatic tissue grew drug-sensitive M. tuberculosis. The patient was treated with a non-standard 4-drug regimen and prednisone, with rapid improvement of symptoms and radiologic abnormalities. Total length of treatment was 12 months. In addition, we review the 12 cases found in literature, and discuss clinical features, diagnostic dilemmas, and approaches to treatment. PMID- 26839787 TI - Abdominal Aortic Dissection in a Patient With Autosomal Dominant Polycystic Kidney Disease After Starting Peritoneal Dialysis. AB - Autosomal dominant polycystic kidney disease (ADPKD), one of the most common genetic disorders, is caused by mutations in the PKD1 or PKD2 gene. ADPKD primarily affects the kidneys, causing the development of multiple bilateral cysts that are characteristic of this condition. Besides renal abnormalities, other manifestations of ADPKD include hepatic, pancreatic, and splenic cysts, intracranial aneurysms, aortic aneurysms, and mitral valve prolapse. Reports of ADPKD-associated abdominal aortic dissections are not rare, but there have been no reports of an ADPKD patient developing intestinal obstruction and abdominal aortic dissection after initiating peritoneal dialysis. Herein, we present one such case. PMID- 26839788 TI - An Adult Case of Paratesticular Spindle Cell Rhabdomyosarcoma. AB - Paratesticular rhabdomyosarcoma (RMS) occurs more frequently in children and is rare in adults. Embryonal RMS is the most common subtype of paratesticular RMS. Spindle cell is a rare variant of embryonal RMS and is associated with a favorable prognosis in children. Data in adults is lacking. We present a case of paratesticular RMS in a 24-year-old man. PMID- 26839789 TI - Metastatic Renal Cell Carcinoma to the Thyroid 23 Years After Nephrectomy. AB - Thyroid carcinoma is an uncommon form of human cancer, with an outstanding overall cure rate. This excellent prognosis is based on the fact that well over 99% of thyroid cancers are primary tumors. Metastatic cancer to the thyroid remains very rare. We report a case of clear cell renal carcinoma metastatic to the thyroid gland 23 years after nephrectomy. PMID- 26839790 TI - Contralateral Adrenal Metastasis of Renal Cell Carcinoma Arising From a Horseshoe Kidney: An Initial Case Report. AB - A 71-year-old woman with a right adrenal mass detected by computed tomography was referred to our institution. Before 33 months, she had undergone a radical heminephrectomy for an 11-cm renal cell carcinoma (RCC) in the left moiety of a horseshoe kidney. The adrenal tumor was diagnosed as the metastasis of RCC. The tumor was subsequently removed in a laparoscopic adrenalectomy by a retroperitoneal approach. Pathologic examination revealed the mass to be the adrenal metastasis of RCC. To our knowledge, this is the initial report of a laparoscopic adrenalectomy for the adrenal metastasis of renal cell carcinoma arising from a horseshoe kidney. PMID- 26839791 TI - Fibrous Pseudotumor of the Tunica Vaginalis Associated With Hydrocele and Testicular Atrophy. AB - Fibrous pseudotumors of the testicular tunics and paratesticular tissue are uncommon lesions. They typically arise as painless scrotal masses that may be associated with hydrocele or history of surgery, trauma, or infection. Although benign, these lesions often clinically indicate malignancy and usually remain undiagnosed preoperatively. Here, we report on a 59-year-old man with fibrous pseudotumor of the tunica vaginalis associated with hydrocele and testicular atrophy. PMID- 26839792 TI - Urinary Bladder Leiomyosarcoma: Primary Surgical Treatment. AB - Cases of bladder leiomyosarcoma represent 0.1% of all nonurothelial tumors. We present a case report of a 73-year-old man who underwent a radical cystoprostatectomy for a high-grade bladder leiomyosarcoma with an ileal diversion. The patient recovered uneventfully and no surgical margins were verified in final pathology. Early follow-up at 3 months shows no signs of computed tomography recurrence and adequate adaptation to ileal diversion. Although bladder sarcomas were once thought to have a grim prognosis, recent studies suggest that adequate surgical treatment is able to achieve optimal cancer control outcomes. PMID- 26839793 TI - Malignant and Metastatic Pheochromocytoma: Case Report and Review of the Literature. AB - Pheochromocytomas are rare neuroendocrine tumors. Although predominantly occurring in the adrenal glands, these tumors can present anywhere along the sympathetic chain. Indeed, classical teaching states that 10% of pheochromocytomas are extra-adrenal and 10% are malignant. We report a case of a 61-year-old female who underwent presumptive cytoreductive nephrectomy and adrenalectomy for renal carcinoma but was instead found to have malignant pheochromocytoma. Proper identification, surgical extirpation, and follow-up are imperative for treatment. We review the classic and current literature regarding management of this uncommon tumor. PMID- 26839794 TI - Mycobacterium bovis Osteomyelitis of the Thoracic Spine Mimicking a Metastatic Lytic Lesion in a Patient Exposed to Intravesicular Bacille Calmette-Guerin Treatment. AB - An 80-year-old man with previous intravesicular bacille Calmette-Guerin therapy developed mass lesions of the lower thoracic spine. Metastatic disease was suspected. The patient underwent a course of radiation; however, biopsy later demonstrated fibrosis and cultures grew Mycobacterium bovis. The patient was treated with a course of isoniazid, rifampin, and ethambutol. PMID- 26839795 TI - High-strength Neodymium Magnetic Beads: A Rare Foreign Body in the Bladder of an Adolescent. AB - This article reports the case of an adolescent who repeatedly inserted high strength magnetic beads into his urethra for erotic reasons. The beads migrated into his bladder requiring a cystostomy to remove them. The available literature is reviewed. PMID- 26839798 TI - Design, Synthesis, and Biological Evaluation of New 2-Phenyl-4H-chromen-4-one Derivatives as Selective Cyclooxygenase-2 Inhibitors. AB - In order to develop new selective COX-2 inhibitors, a new series of 2-phenyl-4H chromen-4-one derivatives possessing a methylsulfonyl pharmacophore group at the para position of the C-4 phenyl ring were designed, synthesized, and evaluated for cyclooxygenase-2 inhibitory activity. In vitro COX-1/COX-2 isozyme inhibition structure-activity studies identified 3-(benzyloxy)-2-[4-(methylsulfonyl)phenyl] 4H-chromen-4-one (5d) as a potent COX-2 inhibitor (IC50 = 0.07 MUM) with a high COX-2 selectivity index (SI = 287.1) comparable to the reference drug celecoxib (COX-2 IC50 = 0.06 MUM; COX-2 SI = 405). A molecular modeling study where 3 (benzyloxy)-2-[4-(methylsulfonyl)phenyl]-4H-chromen-4-one (5d) was docked into the active site of COX-2 showed that the p-MeSO2 substituent on the C-4 phenyl ring was well-oriented in the vicinity of the COX-2 secondary pocket (Arg(513), Val(523), and His(90)) and the carbonyl group of the chromene ring could interact with Ser(530). The structure-activity data acquired indicated that the nature and size of the substituent on the C-3 chromene scaffold are important for COX-2 inhibitory activity. Our results also indicated that the chromene moiety constitutes a suitable template to design new COX-2 inhibitors. PMID- 26839797 TI - Synthesis and Antifungal Evaluation of Novel N-Alkyl Tetra- and Perhydroquinoline Derivatives. AB - A series of novel N-alkyl tetra- and perhydroquinoline derivatives and their hydrochlorides were prepared from tetrahydro- or trans-perhydroquinoline by direct alkylation with alkyl halides and subsequent precipitation with HCl gas. The antimicrobial activity of the resulting amines was evaluated in an agar diffusion assay. The minimal inhibitory concentrations (MIC) of the active compounds were determined by the microdilution method. In contrast to the tetrahydroquinolines, the perhydro analogues showed significant antifungal activity. In an assay for the detection of target enzymes in ergosterol biosynthesis, N-undecylperhydroquinoline was identified as an inhibitor of Delta8,7-isomerase. PMID- 26839799 TI - Synthesis, Characterization, and Cytotoxicity of Some New 5-Aminopyrazole and Pyrazolo[1,5-a]pyrimidine Derivatives. AB - 5-Amino-N-aryl-3-[(4-methoxyphenyl)amino]-1H-pyrazole-4-carboxamides 4a-c were synthesized by the reaction of N-(aryl)-2-cyano-3-[(4-methoxyphenyl)amino]-3 (methylthio)acrylamides 3a-c with hydrazine hydrate in ethanol. The reaction of 5 amino-N-aryl-1H-pyrazoles 4a-c with acetylacetone 5 or 2-(4 methoxybenzylidene)malononitrile 8 yielded the pyrazolo[1,5-a]pyrimidine derivatives 7a-c and 10a-c, respectively. The structures of the synthesized compounds were established based on elemental analysis and spectral data (IR, MS, (1)H-NMR, and (13)C-NMR). Representative examples of the new synthesized products were screened for their in vitro cytotoxic activity against Ehrlich Ascites Carcinoma (EAC) cells. PMID- 26839796 TI - Integration of an [FeFe]-hydrogenase into the anaerobic metabolism of Escherichia coli. AB - Biohydrogen is a potentially useful product of microbial energy metabolism. One approach to engineering biohydrogen production in bacteria is the production of non-native hydrogenase activity in a host cell, for example Escherichia coli. In some microbes, hydrogenase enzymes are linked directly to central metabolism via diaphorase enzymes that utilise NAD+/NADH cofactors. In this work, it was hypothesised that heterologous production of an NAD+/NADH-linked hydrogenase could connect hydrogen production in an E. coli host directly to its central metabolism. To test this, a synthetic operon was designed and characterised encoding an apparently NADH-dependent, hydrogen-evolving [FeFe]-hydrogenase from Caldanaerobacter subterranus. The synthetic operon was stably integrated into the E. coli chromosome and shown to produce an active hydrogenase, however no H2 production was observed. Subsequently, it was found that heterologous co production of a pyruvate::ferredoxin oxidoreductase and ferredoxin from Thermotoga maritima was found to be essential to drive H2 production by this system. This work provides genetic evidence that the Ca.subterranus [FeFe] hydrogenase could be operating in vivo as an electron-confurcating enzyme. PMID- 26839800 TI - Synthesis and Antioxidant Activity of 7-Thio Derivatives of 6,7-Dihydro-1H cyclopenta[d]pyrimidine-2,4(3H,5H)-dione. AB - New 7-thio derivatives of 6,7-dihydro-1H-cyclopenta[d]pyrimidine-2,4(3H,5H)-dione have been synthesized by the reaction of 3-cyclohexyl-7-thio-6,7-dihydro-1H cyclopenta[d]pyrimidine-2,4(3H,5H)-dione with alkylhalogenides. The synthesized compounds were tested for antioxidant activity on the model of Fe(2+)-dependent oxidation of adrenaline in vitro. It was found that the antiradical activity of 7 thio derivatives of 6,7-dihydro-1H-cyclopenta[d]pyrimidine-2,4(3H,5H)-dione significantly depends on the structure of the substituent which is part of the thioether fragment of the base molecule. PMID- 26839801 TI - Synthesis and Characterization of Impurities in the Production Process of Lopinavir. AB - Lopinavir is an antiretroviral drug used for the inhibition of HIV protease. Four related substances of lopinavir were observed during the manufacturing process of lopinavir in the laboratory and they were identified. The present work describes the origin, synthesis, characterization, and control of these related substances. PMID- 26839802 TI - Isolation, Identification, and Characterisation of Degradation Products and the Development and Validation of a Stability-Indicating Method for the Estimation of Impurities in the Tolterodine Tartrate Formulation. AB - A short and sensitive stability-indicating gradient RP-UPLC method was developed for the quantitative determination of process-related impurities and degradation products of tolterodine tartrate in pharmaceutical formulations. The method was developed by using the Waters ACQUITY UPLCTM BEH shield RP18 (2.1 * 100 mm, 1.7 MUm) column with a mobile phase containing a gradient mixture of solvent A and B at a detection wavelength of 210 nm. During the stress study, the degradation products of tolterodine tartrate were well-resolved from tolterodine and its impurities and the mass balances were found to be satisfactory in all the stress conditions, thus proving the stability-indicating capability of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision, ruggedness, and robustness. During the stability (40 degrees C/75% RH, 3 months) analysis of the drug product, one unknown impurity was detected by the above stability-indicating method. The unknown impurity was isolated by preparative HPLC and subjected to mass and NMR studies. Based on the spectral data, the unknown impurity was characterised as 2-(3-amino-1-phenylpropyl)-4-methylphenol (des-N,N-diisopropyl tolterodine). Structural elucidation of the impurity by spectral data is discussed in detail. PMID- 26839803 TI - A Stability-Indicating HPLC Method for the Determination of Fingolimod in Pharmaceutical Dosage Forms. AB - Fingolimod is an immunosuppressive agent which is used for the prophylaxis of organ transplantation rejection or multiple sclerosis treatment. In this study, systematic forced degradation studies on fingolimod bulk powder were performed to develop a stability-indicating HPLC method. Separation of fingolimod and its degradation products was achieved on a Nova-Pak C8 column. The mobile phase was a mixture of potassium dihydrogenphosphate 50 mM (pH 3.0) and acetonitrile (45:55, v/v) at a flow rate of 1 ml/min. The proposed method was linear in the range of 0.125-20 MUg mL(-1). The within-day and between-day coefficients of variation were in the range of 0.6-1.2%. The developed method was successfully applied for the determination of the fingolimod amount in pharmaceutical dosage forms. PMID- 26839804 TI - Identification, Isolation, and Characterization of a New Degradation Impurity in Nafcillin Sodium. AB - A new degradant of Nafcillin Sodium was found at a level of 1.8% w/w during the gradient reversed-phase HPLC analysis in stability storage samples. This impurity was identified by LC-MS and was characterized by (1)H-NMR, (13)C-NMR, LC/MS/MS, elemental analysis, and IR techniques. Based on the structural elucidation data, this impurity was named as N-[(2S)-2-carboxy-2-{[(2-ethoxynaphthalen-1 yl)carbonyl]amino}ethylidene]-3-({N-[(2-ethoxynaphthalen-1 yl)carbonyl]glycyl}sulfanyl)-D-valine. This impurity was prepared by isolation and was co-injected into the HPLC system to confirm the retention time. To the best of our knowledge, this impurity has not been reported elsewhere. The identification and structural elucidation of this degradant impurity has been discussed in detail. PMID- 26839805 TI - Simultaneous Determination and Pharmacokinetic Study of Losartan, Losartan Carboxylic Acid, Ramipril, Ramiprilat, and Hydrochlorothiazide in Rat Plasma by a Liquid Chromatography/Tandem Mass Spectrometry Method. AB - The monitoring of the plasmatic concentrations of cardiovascular drugs is crucial for understanding their pharmacokinetics and pharmacodynamics. A simple, sensitive, specific, and high-throughput liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous estimation and pharmacokinetic study of losartan (LOS), losartan carboxylic acid (LCA), ramipril (RAM), ramiprilate (RPT), and hydrochlorothiazide (HCZ) in rat plasma using irbesartan (IBS) and metolazone (MET) as internal standards (ISs). After solid phase extraction (SPE), analytes and ISs were separated on an Agilent Poroshell 120, EC-C18 (50 mm * 4.6 mm, i.d., 2.7 MUm) column with a mobile phase consisting of methanol/water (85:15, v/v) containing 5 mmol/L ammonium formate and 0.1% formic acid at a flow rate of 0.4 mL/min. The precursor -> product ion transitions for the analytes and ISs were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring (MRM) mode and switching the electrospray ionization (ESI) mode during chromatography from positive (to detect LOS, LCA, RAM, RPT, and IBS) to negative (to detect HCZ and MET). The method was validated as per the FDA guidelines and it exhibited sufficient specificity, accuracy, and precision. The method was found to be linear in the range of 3-3000 ng/mL for LOS and LCA, 0.1-200 ng/mL for RAM and RPT, and 1-1500 ng/mL for HCZ. The described method was successfully applied to the preclinical pharmacokinetic study of analytes after oral administration of a mixture of LOS (10 mg/kg), RAM (1 mg/kg), and HCZ (2.5 mg/kg) in rats. PMID- 26839806 TI - Linking a Pharmaceutical Chemistry Workshop to Pharmacy Practice. AB - This paper describes the design and implementation of a workshop to enhance pharmacy students' appreciation of the importance of chemistry for pharmacy practice. The workshop was designed to form part of the practical work of two modules taught in the second year of the MPharm degree. In this mandatory workshop, second year pharmacy students were required to spot in the dispensary drugs based on their chemical properties like chirality, their origin and chemical structure. The lecturers involved in the workshop showed examples of the application of chemistry in the day to day work of the dispensary (e.g. calculating the dose for a patient in millimoles or how small modifications from a natural product can change its ability to cross the blood-brain-barrier). Feedback from participating students was collected via two survey instruments to examine the impact of the intervention. The survey results showed a clear shift towards a more positive perception by students of the chemistry taught in the MPharm curriculum. PMID- 26839807 TI - Mitigation of Methimazole-Induced Hepatic Injury by Taurine in Mice. AB - Methimazole is the most widely prescribed antithyroid medication in humans. However, hepatotoxicity is a deleterious adverse effect associated with methimazole administration. No specific protective agent has been developed against this complication yet. This study was designed to investigate the role of taurine as a hepatoprotective agent against methimazole-induced liver injury in mice. Different reactive metabolites were proposed to be responsible for methimazole hepatotoxicity. Hence, methimazole-induced liver injury was investigated in intact and/or enzyme-induced animals in the current investigation. Animals were treated with methimazole (200 mg/kg, by gavage), and hepatic injury induced by this drug was investigated in intact and/or enzyme induced groups. Markers such as lipid peroxidation, hepatic glutathione content, alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in plasma, and histopathological changes in the liver of animals were monitored after drug administration. Methimazole caused liver injury as revealed by increased plasma ALT. Furthermore, a significant amount of lipid peroxidation was detected in the drug-treated animals, and hepatic glutathione reservoirs were depleted. Methimazole-induced hepatotoxicity was more severe in enzyme-induced mice. The above-mentioned alterations in hepatotoxicity markers were endorsed by significant histopathological changes in the liver. Taurine administration (1 g/kg, i.p.) effectively alleviated methimazole-induced liver injury in both intact and/or enzyme-induced animals. PMID- 26839808 TI - Curcumin Attenuates Oxidative Stress and Activation of Redox-Sensitive Kinases in High Fructose- and High-Fat-Fed Male Wistar Rats. AB - The present study was carried out to investigate the effects of curcumin on oxidative stress and redox-sensitive kinases in high fructose- and high-fat-fed rats. Sixty rats were randomly divided into six groups with ten animals each. Rats were fed with a standard rodent diet, high fructose diet (60%), and high-fat diet (30%). Curcumin was administered to control, high fructose and high fat diet groups for ten weeks. At the end of the study, body weight and blood glucose levels were measured. The antioxidant enzymes GSH (reduced glutathione), GPx (glutathione peroxidase), and catalase activities were estimated in the blood. MDA, TAS, and TOS were estimated in the plasma, liver, and kidney. Curcumin treatment decreased body weight and blood glucose levels in the rats fed with fructose and high-fat diet. Antioxidant enzymes and plasma TAS were significantly improved by curcumin treatment in high fructose-fed rats, whereas in high-fat-fed rats, there was an increase only in the GPx activity. Curcumin significantly attenuated the elevation of plasma MDA and TOS in both diet groups. Hepatic MDA and TOS were found to be decreased upon curcumin supplementation in both diet groups, whereas a decrease in the renal MDA levels was observed only in fructose treated rats, not in fat-fed rats. Curcumin treatment elevated liver TAS in rats fed only with the fructose-rich diet. Curcumin showed a significant decrease in the oxidative stress index (OSI) in plasma, liver, and kidney tissues in both diet groups. ERK phosphorylation was significantly decreased in both diet groups by curcumin treatment. Similarly, curcumin reduced the phosphorylation of p38 MAPK only in the high fructose-fed rats, not in the high-fat-fed rats. No significant changes were found in JNK phosphorylation in both diet groups. Thus, curcumin may be effective in the management of diet-induced oxidative stress and could be explored as a therapeutic adjuvant against complications associated with obesity and diabetes. PMID- 26839809 TI - Screening of Panamanian Plants for Cosmetic Properties, and HPLC-Based Identification of Constituents with Antioxidant and UV-B Protecting Activities. AB - A library of 600 taxonomically diverse Panamanian plant extracts was screened for DPPH scavenging and UV-B protective activities, and the methanolic extracts of Mosquitoxylum jamaicense, Combretum cacoucia, and Casearia commersionia were submitted to HPLC-based activity profiling. The compounds located in the active time windows were isolated and identified as gallic acid derivatives and flavonoids. Gallic acid methyl ester (3) and digallic acid derivatives (2, 6) showed the highest DPPH scavenging activity (<10 MUg/mL), while protocatechuic acid (7) and isoquercitrin (10) exhibited the highest UV-B protective properties. PMID- 26839810 TI - Enhancing Skin Permeation of Biphenylacetic Acid (BPA) Using Salt Formation with Organic and Alkali Metal Bases. AB - In the present study, a series of organic and alkali metal salts of biphenylacetic acid (BPA) have been prepared and evaluated in vitro for percutaneous drug delivery. The physicochemical properties of BPA salts were determined using solubility measurements, DSC, and IR. The DSC thermogram and FTIR spectra confirmed the salt formation with organic and alkali metal bases. Among the series, salts with organic amines (ethanolamine, diethanolamine, triethanolamine, and diethylamine) had lowered melting points while the alkali metal salt (sodium) had a higher melting point than BPA. The in vitro study showed that salt formation improves the physicochemical properties of BPA, leading to improved permeability through the skin. Amongst all the prepared salts, ethanolamine salt (1b) showed 7.2- and 5.4-fold higher skin permeation than the parent drug at pH 7.4 and 5.0, respectively, using rat skin. PMID- 26839811 TI - In Honour of Em. o. Univ.-Prof. Mag. pharm. Dr. Wolfgang Kubelka on the Occasion of his 80(th) Birthday. PMID- 26839812 TI - [Not Available]. PMID- 26839813 TI - An Alternative Approach to Isoganciclovir: A Prominent Impurity in the Antiviral Drug Ganciclovir. AB - A simple and efficient process for the preparation of (+/-)-9-[(2,3 dihydroxypropoxy)methyl]guanine (isoganciclovir) is described. The synthesis features the preparation of a kinetically and thermodynamically controlled acyclic side chain using masked glycerol and methoxymethyl acetate. The unwanted regioisomers were separated through selective crystallization, which upon deprotection yielded isoganciclovir in good yield. The present work explains the preparation of the acyclic side chain in a simple manner without the aid of any preparative column purification or separation technique. PMID- 26839814 TI - Molecular Docking Studies of Phytocompounds from the Phyllanthus Species as Potential Chronic Pain Modulators. AB - The study of inflammatory pain has been one of the most rapidly advancing and expanding areas of pain research in recent years. Studies from our lab have demonstrated the chronic pain-modulating potential of the Phyllanthus species and their probable interaction with various inflammatory mediators involving enzymes like COX-2 and PGE synthase, cytokines like TNF-alpha and IL-1 beta, and with the NMDA receptor. Inflammatory mediators which play a crucial role in chronic inflammatory hyperalgesia and its subsequent modulation were selected for their interactions with 86 structurally diverse phytoconstituents identified from the Phyllanthus species. The docking analysis of the target proteins with the phytochemical ligands was performed using VLifeMDS software. The docking scores and analysis of the interactions of the phytocompounds with target proteins suggest that important molecules like lupeol, phyllanthin, hypopyllanthin, corilagin, epicatechin, and most of the other compounds have the ability to bind to multiple targets involved in inflammatory hyperalgesia. Our study strongly suggests that the findings of the present study could be exploited in the future for designing ligands in order to obtain novel molecules for the treatment and management of chronic pain. PMID- 26839816 TI - Forced Degradation Behaviour of Fluphenazine Hydrochloride by LC and Characterization of its Oxidative Degradation Product by LC-MS/MS. AB - A novel, stability-indicating high-performance liquid chromatographic (HPLC) method is delivered for the determination of fluphenazine hydrochloride (FPZ) and its degradation products. The forced degradation testing of FPZ was carried out for hydrolytic, oxidative, photolytic, and thermal degradation. The degradation appeared using a reversed-phase C18 column at ambient temperature with a mobile phase comprised of methanol : acetonitrile : (10 mM) ammonium acetate (70:15:15, v/v/v) pH 6.0, adjusted with acetic acid, having a flow rate of 1 ml min(-1) and a detection wavelength at 259 nm. Primarily, the maximum degradation products were formed under oxidative stress conditions. The product was distinguished through LC-MS/MS fragmentation studies. Based on the results, a more complete degradation pathway for the drug could be proposed. The modernized method was found to be precise, accurate, specific, and selective. The method was found to be suitable for the quality control of fluphenazine hydrochloride in the tablet as well as in stability-indicating studies. PMID- 26839815 TI - Development of a Stability-Indicating Stereoselective Method for Quantification of the Enantiomer in the Drug Substance and Pharmaceutical Dosage Form of Rosuvastatin Calcium by an Enhanced Approach. AB - A novel, simple, precise, and stability-indicating stereoselective method was developed and validated for the accurate quantification of the enantiomer in the drug substance and pharmaceutical dosage forms of Rosuvastatin Calcium. The method is capable of quantifying the enantiomer in the presence of other related substances. The chromatographic separation was achieved with an immobilized cellulose stationary phase (Chiralpak IB) 250 mm x 4.6 mm x 5.0 MUm particle size column with a mobile phase containing a mixture of n-hexane, dichloromethane, 2 propanol, and trifluoroacetic acid in the ratio 82:10:8:0.2 (v/v/v/v). The eluted compounds were monitored at 243 nm and the run time was 18 min. Multivariate analysis and statistical tools were used to develop this highly robust method in a short span of time. The stability-indicating power of the method was established by subjecting Rosuvastatin Calcium to the stress conditions (forced degradation) of acid, base, oxidative, thermal, humidity, and photolytic degradation. Major degradation products were identified and found to be well resolved from the enantiomer peak, proving the stability-indicating power of the method. The developed method was validated as per International Conference on Harmonization (ICH) guidelines with respect to specificity, limit of detection and limit of quantification, precision, linearity, accuracy, and robustness. The method exhibited consistent, high-quality recoveries (100 +/- 10%) with a high precision for the enantiomer. Linear regression analysis revealed an excellent correlation between the peak responses and concentrations (r(2) value of 0.9977) for the enantiomer. The method is sensitive enough to quantify the enantiomer above 0.04% and detect the enantiomer above 0.015% in Rosuvastatin Calcium. The stability tests were also performed on the drug substances as per ICH norms. PMID- 26839817 TI - Development of a Forced Degradation Profile of Alosetron by Single Mode Reversed Phase HPLC, LC-MS, and its Validation. AB - Determination of alosetron in the presence of its degradation products was studied and validated by a novel HPLC method. The separation of the drug and its degradation products was achieved with the Jones Chromatography C18 analytical column (150 mm x 4.6 mm; 3 um) with a stationary phase in isocratic elution mode. The mobile phase used was 0.01 M ammonium acetate, pH-adjusted to 3.5 with glacial acetic acid and acetonitrile in the ratio of 75:25 (V/V) at a flow rate of 1 ml/min and UV detection was carried out at 217 nm. Further, the drug was subjected to stress studies for acidic, basic, neutral, oxidative, and thermal degradations as per ICH guidelines and the drug was found to be labile in base hydrolysis and oxidation, while stable in acid, neutral, thermal, and photolytic degradation conditions. An MS study has been performed on the major degradation products to predict the degradation pathway of alosetron. The method provided linear responses over the concentration range of 100-1500 ng/ml and regression analysis showed a correlation coefficient value (r(2)) of 0.994. The LOD and LOQ were found to be 1 ng/ml and 3 ng/ml, respectively. The developed LC method was validated as per ICH guidelines with respect to accuracy, selectivity, precision, linearity, and robustness. PMID- 26839818 TI - Screening of Panamanian Plant Extracts for Pesticidal Properties and HPLC-Based Identification of Active Compounds. AB - A library of 600 taxonomically diverse Panamanian plant extracts was screened for fungicidal, insecticidal, and herbicidal activities. A total of 19 active extracts were submitted to HPLC-based activity profiling, and extracts of Bocconia frutescens, Miconia affinis, Myrcia splendens, Combretum aff. laxum, and Erythroxylum macrophyllum were selected for the isolation of compounds. Chelerythrine (2), macarpine (3), dihydrosanguinarine (5), and arjunolic acid (8) showed moderate-to-good fungicidal activity. Myricetin-3-O-(6''-O-galloyl)-beta galactopyranoside (13) showed moderate insecticidal activity, but no compound with herbicidal activity was identified. PMID- 26839819 TI - Synthesis and Anti-Platelet Activity of Thiosulfonate Derivatives Containing a Quinone Moiety. AB - Thiosulfonate derivatives based on quinones were synthesized for studying "structure-activity relationship" compounds with an acylated and a free amino group. Anti-platelet activity of the synthesized compounds was determined and the influence of substituents on the activity of the derivatives was assessed. PMID- 26839820 TI - A Validated HPLC/MS Limit Test Method for a Potential Genotoxic Impurity in Cilostazol and its Quantification in the API and in the Commercially Available Drug Product. AB - Cilostazol is a selective inhibitor of type 3 phosphodiesterase. 5-(3 Chloropropyl)-1-cyclohexyl-1H-tetrazole, used as an intermediate in the synthesis of cilostazol, has a primary alkyl chloride group, a well-known alerting function for genotoxic activity. Upon request from a regulatory agency, a limit test in accordance with ICH Q2(R1) added with the accuracy of a recovery test of 5-(4 chlorobutyl)-1-cyclohexyl-1H-tetrazole in cilostazol was developed and validated. The application of the method highlighted the need to optimize the purification process to ensure levels of this potential genotoxic impurity in the final active pharmaceutical ingredient below the established limit. Also, the analytical method was suitable to determine the amount of the impurity in samples of the commercially available drug product, which showed the levels to be above the established threshold of toxicological concern (TTC). PMID- 26839821 TI - Validated Stability-Indicating RP-HPLC Method for the Estimation of Degradation Behaviour of Organic Peroxide and Third-Generation Synthetic Retinoids in Topical Pharmaceutical Dosage Formulation. AB - The objective of the current study was to establish a validated stability indicating, high-performance liquid chromatographic method to determine the purity of benzoyl peroxide (BPO) and adapalene (ADP) in the presence of its impurities, forced degradation products, and placebo in pharmaceutical dosage forms. The desired chromatographic separation was achieved on the Kinetex(TM) C18 (250 * 4.6 mm, 5 um) column using gradient elution at 272 nm detection wavelength. The optimized mobile phase consisted of solvent A (mixture of 0.1% v/v glacial acetic acid in water and acetonitrile in the ratio of 80:20 v/v, respectively) and solvent B (mixture of acetonitrile: tetrahydrofuran: methanol in the ratio of 50:30:20 v/v/v, respectively). The stability-indicating capability of the developed method was established by analysing forced degradation samples in which the spectral purity of BPO and ADP along with separation of all degradation products from the analyte peaks was achieved. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision, and robustness. PMID- 26839822 TI - A Rapid, Cost-Effective Pre-Clinical Method to Screen for Pro- or Antiarrhythmic Effects of Substances in an Isolated Heart Preparation. AB - This study describes a rapid, cost-effective pre-clinical method to screen for pro- or antiarrhythmic effects of substances in an isolated heart preparation in line with the regulatory requirements of ICHS7B. The computational method "MFC method" quantifies arrhythmic episodes from isolated perfused hearts based on measuring the variation in the maximum force of contraction. Experiments were performed on hearts isolated from male Wistar rats. Arrhythmias were induced by the addition of tefluthrin or by ligation of the left coronary artery. The "MFC method" accurately measures the maximum force of every myocardial contraction and correlates it with the magnitude of the preceding beat. Arrhythmias were quantified by determining the coefficient of variation in the maximum force of contraction. This method is a useful approach to quickly identify the pro- or antiarrhythmic effects of drugs prior to more detailed analysis; particularly where the effects are varied and not easily classified under the Lambeth Conventions. Therefore, the "MFC method" can be used as a rapid screen for the antiarrhythmic effects of novel compounds or for rapidly determining potential cardiac toxicity. PMID- 26839823 TI - An Efficient, Robust, and Inexpensive Grinding Device for Herbal Samples like Cinchona Bark. AB - An effective, robust, and inexpensive grinding device for the grinding of herb samples like bark and roots was developed by rebuilding a commercially available coffee grinder. The grinder was constructed to be able to provide various particle sizes, to be easy to clean, and to have a minimum of dead volume. The recovery of the sample when grinding as little as 50 mg of crude Cinchona bark was about 60%. Grinding is performed in seconds with no rise in temperature, and the grinder is easily disassembled to be cleaned. The influence of the particle size of the obtained powders on the recovery of analytes in extracts of Cinchona bark was investigated using HPLC. PMID- 26839824 TI - FT-IR Method for the Quantification of Isoflavonol Glycosides in Nutritional Supplements of Soy (Glycine max (L.) MERR.). AB - Due to increasing health consciousness, a lot of food supplements are sold and used. Dietary supplements of Glycine max (L.) MERR. are used as an alternative treatment for menopausal complaints such as hot flashes. Thereby, the effective soy compounds are the isoflavones daidzin, genistin, and glycitin. However, only the total soy extract content of the nutritional supplements is indicated. The aim of this study is to introduce a fast, efficient, and economic Fourier transformation infrared (FT-IR) spectroscopy method to quantify the active ingredients in the complex matrix of soy-based supplements. Five different nutritional supplements of Glycine max (L.) MERR. were purchased from a German pharmacy and were extracted with 80% aqueous methanol. A high-performance liquid chromatography (HPLC) method was used for the separation. The samples were concentrated and measured with infrared spectroscopy. An FT-IR method was established to quantify the active ingredients in the complex matrix of soy-based nutritional supplements. The partial least-squares algorithm was used to develop the method, which enabled the estimation of the content of particular isoflavones (daidzin R(2) = 0.86, glycitin R(2) = 0.94, genistin R(2) = 0.96) and the quantification of the total isoflavone content (R(2) = 0.92) despite peak overlap in the infrared (IR) spectra. The method for the quantification of the isoflavonol glycosides is precise with the standard error of prediction being 13.54%. PMID- 26839825 TI - Influence of Ethanol as a Co-Solvent in Cyclodextrin Inclusion Complexation: A Molecular Dynamics Study. AB - Molecular dynamics (MD) simulations were used to investigate the dynamics and host-guest interactions of the inclusion complexes between a potent anti-HIV agent, UC781, and three different types of cyclodextrins (CDs) including betaCD, 2,6-dimethyl-betaCD (MbetaCD), and 2-hydroxypropyl-betaCD (HPbetaCD) in aqueous solution with ethanol (EtOH) as a co-solvent. The MD simulation results revealed that EtOH as the co-solvent and the type of cyclodextrin affected the inclusion complex formation. From this study, UC781/MbetaCD provided the most stable inclusion complex. The competition for the cavity of betaCD between UC781 and EtOH and the ensuing occupation of betaCD cavities by EtOH resulted in a weaker interaction between betaCD and UC781. In HPbetaCD, a supramolecular complex of UC781-HPbetaCD-EtOH was formed. The EtOH could easily fill the residual void space of the interior of unoccupied HPbetaCD due to the movement of UC781. In MbetaCD, the strong hydrogen bond interactions between the UC781 amide group and the secondary hydroxyl groups of MbetaCD significantly stabilized the inclusion complex in the presence of EtOH. PMID- 26839826 TI - Suppression of IgM Proteolysis by Conformational Stabilization Through Excipients. AB - Protease activity from host cell lines may cause product loss or affect the quality of recombinant proteins. In this study, we showed that excipients like glycine and sorbitol reduce the proteolysis of an immunoglobulin M (IgM) in the presence of added proteases like alpha-chymotrypsin, papain, and pepsin. The activity of the proteases in the IgM-protective environments was conserved or even enhanced as tested using low molecular weight substrates. Thus, a higher resistance against proteolytic degradation appears to be caused by the conformational stabilization of the IgM due to preferential exclusion of sorbitol and glycine. PMID- 26839827 TI - Improved Automated Radiosynthesis of [(11)C]PBR28. AB - Microglial activation is commonly identified by elevated levels of the 18 kDa translocator protein (TSPO) in response to several inflammatory processes. [(11)C]PBR28 is one of the most promising PET tracers to image TSPO in both human and non-human primates. In this study, we optimized the radiolabeling procedure of [(11)C]PBR28 for higher radiochemical yield, radiochemical purity, and specific activity, which can be easily translated to any automated module for clinical trials. Time-activity curves (TACs) derived from the dynamic PET imaging of male rhesus monkey brains demonstrated that [(11)C]PBR28 had suitable kinetics with radiotracer accumulation observed in the caudate, putamen, cerebellum, and frontal cortex region. PMID- 26839828 TI - Synthesis and In Vitro Biological Evaluation of 1,3,4-Oxadiazol-2(3H)-one and Tetrahydropyridazine-3,6-dione Derivatives of Fatty Acids. AB - Herein we report saturated and unsaturated fatty acid derivatives of 1,3,4 oxadiazol-2(3H)-one and tetrahydropyridazine-3,6-dione as new potential anticancer agents. All the synthesised compounds were characterised by IR, (1)H NMR, (13)C-NMR, and mass spectral data. The relative sensitivity of three cancer cell lines varied depending on the nature of the compound. Among the most effective anticancer compounds studied, 3b and 6b displayed remarkable anticancer activity against the MDA-MB-231 and KCL-22 lines, respectively. On the other hand, compound 3c was found to be most sensitive to nearly all the tested cell lines, MDA-MB-231, KCL-22, and HeLa. PMID- 26839830 TI - Cost-Effective Isolation of a Process Impurity of Pregabalin. AB - Cost-effective isolation methods were developed on preparative HPLC, flash LC, and simulated moving bed (SMB) to prepare the process impurity, 3-(aminomethyl)-5 methylhex-4-enoic acid (4-ene impurity), of pregabalin. By a thorough experimental study on the different isolation techniques available, it was concluded that SMB was the most cost-effective. Hence, it was a continuous chromatography that utilized the advantage of SMB so that a high quantity of the impurity was generated in a short period of time. SMB was equipped with eight reversed-phased columns and was used to separate the process impurity of pregabalin. The effects of flow rate in zone 2 (Q2) and 3 (Q3), as well as switching time, on the operating performance parameters like purity, productivity, and desorbent consumption were studied. Operating conditions leading to more than 90% purity in the raffinate outlet stream were identified, together with those achieving optimal performance. All of these developed methods are novel, cost-effective, and can be applied to the isolation of other process- and stability-related impurities of pregabalin. PMID- 26839829 TI - Synthesis of Isomeric and Potent Impurities of the Triazole-Based Antifungal Drug Voriconazole. AB - We describe the synthesis of two positional isomers and a desfluoro impurity of Voriconazole starting with Friedel-Crafts acylation of mono- and difluorobenzene. These isomers are the crucial components in determining the quality of Voriconazole during its manufacturing from the key raw material, 1-(2,4 difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-one. All the prepared impurities were characterized by IR, (1)H-NMR, (13)C-NMR, and mass spectral data. PMID- 26839831 TI - A Competent and Commercially Viable Process for the Synthesis of the Anti Hypertensive Drug Olmesartan Medoxomil. AB - Drug product purity and potency are of most significance in the regulatory market as we notice many recalled batches worldwide, particularly in the US and Japan. Olmesartan Medoxomil is an anti-hypertensive drug. The present invention relates to a process for the preparation of Olmesartan Medoxomil with 99.9% purity in an overall 62% yield. The synthesis includes three isolations and one purification with easy plant operations. This process describes the formation and control of each individual impurity in all stages. This process for Olmesartan Medoxomil and its intermediates is competent for industrial production in very short reaction time intervals with an appreciable yield and high purity. PMID- 26839832 TI - Polysaccharide-Rich Fraction of Noni Fruit (Morinda citrifolia L.) as Doxorubicin Co-Chemotherapy: Evaluation of Catalase, Macrophages, and TCD8+ Lymphocytes. AB - Noni fruit (Morinda citrifolia L.) has been acknowledged for its cytotoxic and immunostimulatory activity. Our previous results on the immunomodulatory effect of a noni juice polysaccharide-rich fraction encouraged this research to evaluate the potency of the polysaccharide-rich fraction as co-chemotherapy with doxorubicin (DOX) administration. Macrophage activity (MA) was evaluated with the latex bead method. The phagocytic index (PI) was measured as the number of latex beads ingested by 100 macrophages, while the phagocytosis ratio (PR) was indicated by the percentage of macrophages that ingested three or more latex beads. The CEC was evaluated by using a commercial assay kit, while CD8+ T lymphocyte proliferation was evaluated using a flowcytometry method following in vivo administration. Thirty male Wistar rats were divided into five groups (n = 6 each). The control group received DOX via i.p. at a concentration of 4.67 mg/kg BW on days 1 and 4; four treatment groups received PF p.o. at a concentration of 25; 50; 100; 200 mg/kg BW daily, respectively, and additionally DOX i.p. 4.67 mg/kg BW (days 1 and 4) for 7 days. The phagocytic activity was not affected significantly by PF administration compared to the Dox control, but PF administration at a dose of 25 and 50 mg/kg BW has been proven to increase TCD8+ cell proliferation in combination with DOX. The catalase concentration, on the other hand, significantly decreased following PF administration at a dose of 100 mg/kg BW. The results suggest that the polysaccharide-rich fraction of noni juice might induce immunomodulatory effects via TCD8+ activation, have antioxidant activity, and thus might be a potential candidate to be used as an adjuvant to DOX chemotherapy. PMID- 26839833 TI - Metabolite Profiling of Justicia gendarussa Burm. f. Leaves Using UPLC-UHR-QTOF MS. AB - An ultra-performance liquid chromatography ultra-high-resolution quadrupole-time of-flight-mass spectrometry (UPLC-UHR-QTOF-MS) metabolite profiling ofxs Justicia gendarussa Burm. f. leaves was performed. PCA and HCA analyses were applied to observe the clustering patterns and inter-sample relationships. It seemed that the concentrations of Ca, P, and Cu in the soil could affect the metabolite profiles of Justicia gendarussa. Six significant metabolites were proposed. PMID- 26839834 TI - Improved Pharmacokinetics of Aceclofenac Immediate Release Tablets Incorporating its Inclusion Complex with Hydroxypropyl-beta-Cyclodextrin. AB - The present investigation reports the various pharmacokinetic parameters of immediate release aceclofenac tablets incorporating its inclusion complex with hydroxypropyl-beta-cyclodextrin. The tablets were prepared using aceclofenac: hydroxypropyl-beta-cyclodextrin in a 1:1 molar ratio by the direct compression method (TKN). The results were compared with those of the marketed brand (MKT) and pure drug (TAC). The P-values indicated that mean plasma concentrations were significantly different among all three formulations administered (P<0.05, P<0.01). TKN showed significantly higher plasma levels when compared to the pure drug (P<0.01). The Cmax and AUC(0-infinity) of TKN were significantly higher (P<0.05) compared to the pure drug and marketed formulation. Furthermore, the first-order overall elimination rate constant (Kel) of TKN was also significantly higher (P<0.05) compared to the pure drug and its marketed formulation. These results suggested that tablets prepared by incorporating the AC-HPbetaCD inclusion complex (TKN) would provide a more rapid onset of pharmacological effects in comparison to the marketed formulation and pure drug. PMID- 26839835 TI - Dosage Form Data Used for Estimating Pediatric Antibiotic Use. AB - We aimed to report a simple estimation method to enable quantification of pediatric antibiotic exposure in large aggregated datasets. Secondly, we aimed to quantify and benchmark Hungarian pediatric antibiotic use. First we intended to examine whether a correlation existed between dosage form data and the patient's age. Therefore, issued prescriptions were analyzed in pharmacies. As a correlation was found between the share of liquid oral antibacterial products and the rate of pediatric antibiotic prescriptions (R=0.884; p<0.001), we extrapolated this finding to a large aggregated dataset and estimated that 34.6% of prescriptions were issued for pediatric cases (95% confidence interval: 19.7 60.0). Taking into account the demography of the population, children were exposed to antibiotics three times more often than adults with a corresponding annual prescription rate of 2.6. We demonstrated that simple drug-related data can be linked to a patient-related measure as we found strong associations between dosage form data and patients' age. Based on this association, massive pediatric antibiotic exposure was found. Due to the general availability of dosage form data and the ease of the estimation method, the reported concept can be used to quantify pediatric antibiotic use in large aggregated datasets or when age stratification is absent. PMID- 26839836 TI - The Role of Polydimethylsiloxane in the Molecular Structure of Silica Xerogels Intended for Drug Carriers. AB - The aim of this study was to prepare and examine polymer/oxide xerogels with metronidazole (MT) as delivery systems for the local application of a drug to a bone. The nanoporous SiO2-CaO and PDMS-modified SiO2-CaO xerogel materials with different amounts of the polymer, polydimethylsiloxane (PDMS), were prepared by the sol-gel method. Characterization assays comprised the analysis of the composite materials by using Fourier transform infrared spectroscopy (FTIR), determining the specific surface area of solids (BET), using X-ray powder diffraction (XRD) and scanning electron microscope (SEM) techniques, and further monitoring in the ultraviolet and visible light regions (UV-Vis) of the in vitro release of the drug (metronidazole) over time. According to these results, the bioactive character and chemical stability of PDMS-modified silica xerogels have been proven. The release of MT from xerogels was strongly correlated with the composition of the matrix. In comparison with the pure oxide matrix, PDMS modified matrices accelerated the release of the drug through its bigger pores, and additionally, on account of weaker interactions with the drug. The obtained results for the xerogel composites suggest that the metronidazole-loaded xerogels could be promising candidates for formulations in local delivery systems particularly to bone. PMID- 26839837 TI - Activation of HIV-1 with Nanoparticle-Packaged Small-Molecule Protein Phosphatase 1-Targeting Compound. AB - Complete eradication of HIV-1 infection is impeded by the existence of latent HIV 1 reservoirs in which the integrated HIV-1 provirus is transcriptionally inactive. Activation of HIV-1 transcription requires the viral Tat protein and host cell factors, including protein phosphatase-1 (PP1). We previously developed a library of small compounds that targeted PP1 and identified a compound, SMAPP1, which induced HIV-1 transcription. However, this compound has a limited bioavailability in vivo and may not be able to reach HIV-1-infected cells and induce HIV-1 transcription in patients. We packaged SMAPP1 in polymeric polyethylene glycol polymethyl methacrylate nanoparticles and analyzed its release and the effect on HIV-1 transcription in a cell culture. SMAPP1 was efficiently packaged in the nanoparticles and released during a 120-hr period. Treatment of the HIV-1-infected cells with the SMAPP1-loaded nanoparticles induced HIV-1 transcription. Thus, nanoparticles loaded with HIV-1-targeting compounds might be useful for future anti-HIV-1 therapeutics. PMID- 26839838 TI - The Effective Synthesis of N-(Arylalkyl)-1-R-4-hydroxy-2,2-dioxo- 1H-2lambda(6),1 benzothiazine-3-carboxamides as Promising Analgesics of a New Chemical Class. AB - A new, effective preparative method has been proposed and the synthesis of a series of N-(arylalkyl)-1-R-4-hydroxy-2,2-dioxo-1H-2lambda(6),1-benzothiazine-3 car-boxamides has been carried out. It has been shown that amidation of alkyl 1-R 4-hydroxy-2,2-dioxo-1H-2lambda(6),1-benzothiazine-3-carboxylates with arylalkyl amines in boiling xylene proceeds with good yield and purity to the corresponding N-(arylalkyl)-amides. However, the presence of water in the reaction mixture has been shown to cause the formation of specific impurities: N-(arylalkyl)-1-R-2,2 dioxo-1H-2lambda(6),1-benzothiazin-4-amines. According to the results of the pharmacological studies, powerful analgesics have been found among the substances synthesized. PMID- 26839839 TI - A Novel, Rapid, and Validated Stability-Indicating UPLC Method for the Estimation of Drotaverine Hydrochloride and Ibuprofen Impurities in Oral Solid Dosage Form. AB - A novel, stability-indicating, reversed-phase ultra-performance liquid chromatographic (RP-UPLC) method was developed for the determination of pure drotaverine hydrochloride and ibuprofen in the presence of their impurities and degradation products. The method was developed using a Waters UPLC BEH C18, 100 * 2.1 mm, 1.7 um column with a flow rate of 0.3 mL/min and detector wavelength at 210 nm. The mobile phase consisted of potassium dihydrogen orthophosphate buffer and acetonitrile. Drotaverine hydrochloride and ibuprofen were subjected to the stress conditions of oxidative, acid, base, photolytic, and thermal degradation. Degradation products resulting from the stress studies were well-resolved, thus confirming the test method as stability-indicating. Validation of the method was carried out as per International Conference on Harmonization guidelines. PMID- 26839840 TI - Development and Validation of a Stability-Indicating RP-UPLC Method for the Estimation of Impurities in Cinacalcet Hydrochloride API and its Formulation. AB - A sensitive, stability-indicating, gradient reversed-phase ultra-performance liquid chromatography method has been developed for the quantitative estimation of cinacalcet hydrochloride impurities in active pharmaceutical ingredients and pharmaceutical formulations. Efficient chromatographic separation was achieved on an Acquity BEH Shield RP18, 100 * 2.1 mm, 1.7 um column with the mobile phase containing pH 6.6 phosphate buffer and acetonitrile. The flow rate of the mobile phase was 0.3 mL min(-1) with a column temperature of 35 degrees C and detection wavelength at 223 nm. The relative response factor values of (+)-R-1-(1 Naphthyl)ethylamine, regioisomer, diastereomer isomer-1, and diastereomer isomer 2 were 1.79, 0.99, 0.89, and 0.88, respectively. The cinacalcet hydrochloride formulation sample was subjected to the stress conditions of acid, base, oxidative, hydrolytic, thermal, humidity, and photolytic degradation. Cinacalcet hydrochloride was found to degrade significantly under the peroxide stress conditions. The degradation products were well-resolved from cinacalcet hydrochloride and its impurities. The peak purity test results confirmed that the cinacalcet hydrochloride peak was homogenous in all stress samples and the mass balance was found to be more than 96%, thus proving the stability-indicating power of the method. The developed method was validated according to ICH guidelines. PMID- 26839841 TI - Simultaneous Estimation of Hydrochlorothiazide, Hydralazine Hydrochloride, and Reserpine Using PCA, NAS, and NAS-PCA. AB - In this study, new and feasible UV-visible spectrophotometric and multivariate spectrophotometric methods were described for the simultaneous determination of hydrochlorothiazide (HCTZ), hydralazine hydrochloride (H.HCl), and reserpine (RES) in combined pharmaceutical tablets. Methanol was used as a solvent for analysis and the whole UV region was scanned from 200-400 nm. The resolution was obtained by using multivariate methods such as the net analyte signal method (NAS), principal component analysis (PCA), and net analyte signal-principal component analysis (NAS-PCA) applied to the UV spectra of the mixture. The results obtained from all of the three methods were compared. NAS-PCA showed a lot of resolved data as compared to NAS and PCA. Thus, the NAS-PCA technique is a combination of NAS and PCA methods which is advantageous to obtain the information from overlapping results. PMID- 26839842 TI - Development of an Ion Chromatography Method for Analysis of Organic Anions (Fumarate, Oxalate, Succinate, and Tartrate) in Single Chromatographic Conditions. AB - A single organic counterion analysis method was developed by using an ion chromatography separation technique and conductivity detector. This allows the rapid characterization of an API to support clinical studies and to fulfil the regulatory requirements for the quantitation of fumarate, oxalate, succinate, and tartrate counterions in active pharmaceutical ingredients (quetiapine fumarate, escitalopram oxalate, sumatriptan succinate, and tolterodine tartrate). The method was developed by using the Metrohm Metrosep A Supp 1 (250 * 4.0 mm, 5.0 um particle size) column with a mobile phase containing an isocratic mixture of solution A: 7.5 mM sodium carbonate and 2.0 mM sodium bicarbonate in Milli-Q water and solution B: acetonitrile. The flow rate was set at 1.0 mL/min and the run time was 25 minutes. The developed method was validated as per ICH guidelines, and the method parameters were chosen to ensure the spontaneous quantitation of all four anions. The method was validated for all four anions to demonstrate the applicability of this method to common anions present in various APIs. PMID- 26839843 TI - Characterization of the Oxidative Degradation Product of Darunavir by LC-MS/MS. AB - A rapid, selective, and reliable LC-MS(n) method has been developed and validated for the isolation and structural characterization of the degradation product of darunavir (DRV). DRV, an HIV-1 protease inhibitor, was subjected to intrinsic oxidative stress conditions using 30% hydrogen peroxide and the degradation profile was studied. The oxidative degradation of DRV resulted in one degradation product. The unknown degradation product was separated on a Hibar Purospher C18 (250 mm * 4.6 mm; 5 um) column by using 0.01 M ammonium formate (pH 3.0) and acetonitrile as mobile phase in the ratio of 50:50, v/v. The eluents were monitored at 263 nm using a UV detector. The isolated degradation product was characterized by UPLC-Q-TOF and its fragmentation pathway was proposed. The proposed structure of the degradation product was confirmed by HRMS analysis. The developed stability-indicating LC method was validated with respect to accuracy, precision, specificity/selectivity, and linearity. No prior reports were found in the literature about the oxidative degradation behavior of DRV. PMID- 26839844 TI - Effects of Methyl Jasmonate on Acute Stress Responses in Mice Subjected to Forced Swim and Anoxic Tests. AB - Methyl jasmonate (MJ) is an anti-stress hormone released by plants in response to external stressors and aids adaptation to stress. In this study, we evaluated the anti-stress activity of MJ using the forced swim endurance test (FSET) and anoxic tolerance test in mice. Male Swiss mice were given MJ (25-100 mg/kg, i.p) 30 min before the FSET and anoxic test were carried out. The first occurrence of immobility, duration of immobility, time spent in active swimming, and latency to exhaustion were assessed in the FSET. The onset to anoxic convulsion was measured in the anoxic tolerance test. MJ significantly (p < 0.05) delayed the first occurrence of immobility and shortened the period of immobility, which indicates anti-stress property. MJ also increased the time spent in active swimming and prolonged the latency to exhaustion, which further suggests anti-stress activity. In addition, it also exhibited anti-stress property as evidenced by prolonged latency to first appearance of anoxic convulsions. The results of this study suggest that MJ demonstrated anti-stress activity and may be useful as an energizer in times of body weakness or exhaustion. Although more studies are necessary before concluding on how MJ exerts its anti-stress activity, the present data suggest an action similar to adaptogens in boosting energy and resilience in the face of stress. PMID- 26839845 TI - Pharmacokinetic Parameters Determination and In Vitro-In Vivo Correlation of Ileocolonic-Targeted pH-Responsive Coated Mini-Tablets of Naproxen. AB - This research work aims to determine the pharmacokinetic parameters and in vitro in vivo correlation of the selected ileocolonic-targeted coated mini-tablet filled capsule formulation of naproxen. The pure suspension and coated mini tablet filled capsule formulation of naproxen were administered to adult albino rabbits through the oral route. The samples were analyzed for naproxen by an HPLC method. For the pure drug suspension, the peak plasma concentration was found as 8.499+/-0.029 MUg/ml at 1.139+/-0.010 hours and the half-life was found to be 9.459+/-0.387 hours, whereas for the formulation the peak plasma concentration was found as 6.814+/-0.037 MUg/ml at 8.042+/-0.069 hours and the half-life was found to be 19.657+/-0.359 hours. This decreased the peak plasma concentration at a delayed time and increased the half-life of the capsule formulation in comparison with the pure drug suspension which showed that naproxen was only targeted to the ileocolonic region. A significant in vitro-in vivo correlation (i.e. R(2)=0.9901) was also obtained. Thus, the results of these findings suggest that naproxen formulated as coated mini-tablets can be suitable for targeted ileocolonic drug delivery. PMID- 26839846 TI - Physicochemical and Microbiological Stability of the Extemporaneous Sildenafil Citrate Oral Suspension. AB - Sildenafil is a potent and selective phosphodiesterase-5 inhibitor that is effectively used in the treatment of pulmonary arterial hypertension. In several countries, hospital pharmacists prepare the drug in an extemporaneous liquid preparation as there are no liquid formulations available for pediatric and adult uses. The purpose of this study was to evaluate the stability of an extemporaneous sildenafil citrate oral suspension for 90 days, according to the ASEAN guideline on stability studies of drug products. The results showed that the preparation was a white suspension with a sweet taste. It was a viscous and weakly acidic mixture with pseudoplastic behavior. The drug content was in the range between 99.23% and 102.23%, and the microbial examination met the general requirements throughout the study period. Therefore, the extemporaneously compounded sildenafil suspensions were physically, chemically, and microbiologically stable for at least 90 days when stored at 30 degrees and 40 degrees C. Furthermore, the in-use stability study showed that the preparations had acceptable attributes at least 14 days after the first-time use. This might provide an alternative option when the commercial suspension is unavailable. PMID- 26839847 TI - Formulation and Evaluation of Controlled Release Floating Microballoons of Stavudine. AB - The aim of this study was to formulate and evaluate stavudine floating microballoons for controlled drug release. Initially, the drug-loaded low-density granular pellets were prepared with hydroxypropyl methylcellulose E5 grade and by using isopropyl alcohol as a granulating fluid. Further, the low-density granular pellets were subjected to microencapsulation by an emulsion evaporation technique using ethyl cellulose 7 cps and Eudragit S 100 as coating polymers and 1% w/v polyethylene glycol 400 as aqueous phase. The prepared microballoons were characterized for their particle size analysis, angle of repose, and compressibility index. The in vitro release studies were performed in 0.1 N HCl as medium. The prepared microballoons were free-flowing and spherical in shape. From all the formulations, F5E and F5F can be considered as promising controlled release floating microballoons of stavudine providing first-order release over a period of 12 hours, with a minimum floating lag time of 1 minute. It was found that the ratio of the drug & polymer, stirring speed, and concentration of surfactant were the most significant variables which influenced the size of the stavudine microballoons under the applied experimental conditions. PMID- 26839848 TI - Host-Guest Inclusion Complexes between Amlodipine Enantiomers in the Biphasic Recognition Chiral Extraction System using Tartaric Acid and beta-Cyclodextrin Derivatives as Positive Confirmation by using their Enantioselective Extraction. AB - The current work reports an extended theoretical study from our previous experimental work for the enantioselective extraction of amlodipine enantiomers in a biphasic recognition chiral extraction system (BRCES) consisting of hydrophobic D-diisopropyl tartrate dissolved in organic phase (n-decanol) and hydrophilic hydroxypropyl-beta-cyclodextrin (HP-beta-CD) in aqueous phase (acetate buffer) which preferentially recognize the R-enantiomer and S enantiomer, respectively. The calculations were simulated using a semi-empirical PM3 method as a part of the Gaussian09 software package and were used to optimize the structures of the hosts, guests, and host-guest complexes in the gas phase without any restrictions. It was found that HP-beta-CD has the strongest recognition ability among the three beta-CD derivatives studied, namely HP-beta CD, hydroxyethyl-beta-cyclodextrin (HE-beta-CD), and methylated-beta-cyclodextrin (Me-beta-CD), due to the large interaction energies (Ecomp = -14.3025 kcal/ mol), while D-diisopropyl tartrate has the strongest ability among the four tartaric acid derivatives studied namely; L-diisopropyl tartrate, D-diisopropyl tartrate, L-diethyl tartrate, and D-diethyl tartrate (Ecomp = -5.9964 kcal/ mol). The computational calculations for the enantioselective partitioning of amlodipine enantiomers rationalized the reasons for the different behaviors for this extraction. The present theoretical results may be informative to scientists who are devoting themselves to developing models for their experimental parts or for enhancing the hydrophobic drug solubility in drug delivery systems. PMID- 26839849 TI - Endovascular Repair of Blunt Traumatic Thoracic Aortic Injuries. PMID- 26839850 TI - Predictive Potential of Heart Rate Complexity Measurement: An Indication for Laparotomy Following Solid Organ Injury. AB - BACKGROUND: Nonlinear analysis of heart rate variability (HRV) has been recently used as a predictor of prognosis in trauma patients. OBJECTIVES: We applied nonlinear analysis of HRV in patients with blunt trauma and intraperitoneal bleeding to assess our ability to predict the outcome of conservative management. PATIENTS AND METHODS: An analysis of electrocardiography (ECG) from 120 patients with blunt trauma was conducted at the onset of admission to the emergency department. ECGs of 65 patients were excluded due to inadequacy of noise-free length. Of the remaining 55 patients, 47 survived (S group) and eight patients died in the hospital (Non-S group). Nineteen patients were found to have intra abdominal bleeding, eight of which ultimately underwent laparotomy to control bleeding (Op group) and 11 underwent successful non-operative management (non Op). Demographic data including vital signs, glasgow coma scale (GCS), arterial blood gas and injury severity scores (ISS) were recorded. Heart rate complexity (HRC) methods, including entropy, were used to analyze the ECG. RESULTS: There were no differences in age, gender, heart rate (HR) and blood pressure between the S and Non-S groups. However, approximate entropy, used as a method of HRC measurement, and GCS were significantly higher in S group, compared to the Non-S group. The base deficit and ISS were significantly higher in the Non-S group. Regarding age, sex, ISS, base deficit, vital signs and GCS, no difference was found between Op and Non-Op groups. Approximate entropy was significantly lower in the Op group, compared to the Non-Op group. CONCLUSIONS: The loss of HRC at the onset of admission may predict mortality in patients with blunt trauma. Lower entropy, in recently admitted patients with intra-abdominal bleeding, may indicate laparotomy when the vital signs are stable. PMID- 26839851 TI - Topical Nicotinamide Improves Tissue Regeneration in Excisional Full-Thickness Skin Wounds: A Stereological and Pathological Study. AB - BACKGROUND: Nicotinamide (NA), the active form of vitamin-B3, is hypothesized to have positive effects on the process of wound healing; it has anti-inflammatory, antioxidant, and immunomodulatory properties, as well as an epithelization inducing action. OBJECTIVES: In the present study, we aimed to determine the effects of topical administration of NA on skin wounds, based on histomorphometrical and pathological criteria. MATERIALS AND METHODS: In this study, 36 male Sprague-Dawley rats (220 +/- 20 g each), with 1 cm(2) circular full-thickness wounds on their backs were divided into three groups (n = 12): NA group, was treated daily with a Nicotinamide 2% gel , untreated group (control), and base group, which were treated with the vehicle (base) of the gel (carboxymethylcellulose). Skin biopsies were prepared for microscopic analyses. Inflammation, granulation tissue formation, ulceration, epithelization, wound closure rate, fibroblast proliferation, collagen synthesis, and vascularization were studied criteria. RESULTS: The results revealed that besides improving the wound healing by its anti-inflammatory, antioxidant, and epithelization inducing effects, NA also improved tissue regeneration through the increment of fibroblast proliferation, collagen synthesis, and vascularization. CONCLUSIONS: In spite of the few reported side effects, NA can be introduced as an effective agent on the wound healing process, an adjuvant therapy and possibly a treatment by itself. However, its chemical characteristics, as well as possible adverse effects warrants further research. PMID- 26839852 TI - Needle-Stick Injuries Among Healthcare Workers in a Teaching Hospital. AB - BACKGROUND: Needle-Stick Injuries (NSIs) are among the hazards and problems that can expose health workers to infections. OBJECTIVES: This study aimed to determine the rate of NSIs in a teaching hospital in Tehran, Iran. MATERIALS AND METHODS: This cross-sectional, analytical and descriptive study was conducted at one of the teaching hospitals in Tehran, Iran, in 2013. The study population was 344 employees in various occupational groups selected via census. Data were collected using a researcher-made questionnaire. The collected data were analyzed using some statistical tests, including independent-samples t-test with SPSS software version 21.0. RESULTS: The results showed that only 50.2% of injuries had been reported; 67.8% of all participants (n = 211) had at least one NSI. Most NSIs had been reported in the emergency department (33.5%). Most participants mentioned the injection syringe needles as the main cause of their injuries (71.1% of all NSIs). Among NSIs, those caused by insulin syringe needles (6.2%) were the second cause. In this study, females had NSIs more than males. There was a statistically significant relationship between sex and the rate of NSIs (P < 0.05). CONCLUSIONS: Considering the high rate of occupational injuries, further preventive measures should be implemented to prevent these injuries from occurring. Providing initial and continuing training for employees is very important. Directing special attention to emergency department employees may be effective in reducing occupational injuries. PMID- 26839853 TI - Success Rate and Complications of Comminuted Intra-Articular Distal Radius Fracture Treatment via Closed Reduction and Use of a Mini-External Fixator. AB - BACKGROUND: Intra-articular fracture of the distal radius is extremely common; however, the management of this fracture is controversial. OBJECTIVES: With regard to the importance of intra-articular fracture of the distal radius and the best treatment method for the fracture, we sought to assess the success rate following the treatment of comminuted intra-articular fractures of the distal radius via closed reduction and use of a mini-external fixator. PATIENTS AND METHODS: This longitudinal retrospective study was undertaken at our department of orthopedics via assessment of radiographs and patient files of those referred from 2006 to 2013. Radiographic criteria included the degree of angulation and shortening of the radius. Data were analyzed using SPSS 18 software and were presented as mean +/- standard deviation (SD). The significance level was set at P <= 0.05. RESULTS: Overall, >= 2 mm shortening of the radius was seen in 28% of the patients, 53% had 2 - 5 mm radial shortening and 19% of the patients had more than 5 mm shortening of the radius. Most of the participants had acceptable outcomes. The mean angulation was 6.28 +/- 2.85 degrees and the mean shortening was 3.92 +/- 2.22. Thirty-nine percent of the patients had an angulation of less than 5 mm, 56% and 5% had an angulation of 5 - 10 mm and more than 10 mm, respectively. CONCLUSIONS: The results of our study showed that the mini-external fixator is a good and effective treatment option for obtaining radial length, angulation and bony union in intra-articular fractures of the distal radius. PMID- 26839854 TI - Assessment of Electrosurgery Burns in Cardiac Surgery. AB - BACKGROUND: Monopolar surgery is applied mostly in major operations, while bipolar is used in delicate ones. Attention must be paid in electrosurgery application to avoid electrical burns. OBJECTIVES: We aimed to assess factors associated with electrosurgery burns in cardiac surgery operating rooms. PATIENTS AND METHODS: This was a case-control study in which two groups of 150 patients undergoing cardiac surgery in Imam Khomeini Hospital were recruited. Several factors like gender, age, operation duration, smoking, diseases, infection, atopia, , immunosuppressive drugs use, hepatic cirrhosis, and pulmonary diseases were compared between the two groups. Patients were observed for 24 hours for development of any burn related to the operation. Data was analyzed using SPSS v.11.5, by Chi square and T-test. RESULTS: Patients in the two groups were similar except for two factors. DM and pulmonary diseases which showed significant differences (P = 0.005 and P = 0.002 respectively). Seventy-five patients from controls and 35 from the study group developed burns, which was significant (P ? 0.0001). CONCLUSIONS: None of the factors were significantly related to developing burns. The differences between the two groups highlights the importance of systems modifications to lessen the incidence of burns. PMID- 26839856 TI - Recovery of Facial Nerve Paralysis After Temporal Nerve Reconstruction: A Case Report. AB - INTRODUCTION: Facial paralysis is common following accidents, trauma, viral infection or tumors. CASE PRESENTATION: A 24-year-old male patient was referred to us with a history of sharp penetrating trauma to the right temporal region causing unilateral paralysis of the muscles of the right forehead. He was unable to scowl or elevate his right eyebrow and there were no folds on his right forehead. Anastomosis of branches of the temporal nerve was done one month after trauma following regular physical therapy sessions, outcome was good and paralysis of the muscles of the right forehead improved after several months. CONCLUSIONS: Immediate repair of the facial nerve injury will improve the process of recovery and rehabilitation of the face and forehead muscles and may play a very important role in the patient's mental satisfaction and improve their quality of life. PMID- 26839857 TI - Reattachment of a Fractured Anterior Tooth Segment With Pulp Exposure via Er:YAG and Nd:YAG Lasers. AB - INTRODUCTION: The reattachment of a dental fragment may be performed for treatment of traumatized anterior teeth, both in cases of simple coronal fracture (enamel and superficial dentin) and in those with complicated coronal fracture (deep dentin with pulp exposure). A major part of this procedure is the adhesion technique, which was described for the first time by Buonocore in 1955. This clinical case demonstrates the use of Er:YAG and Nd:YAG lasers in fragment reattachment of a traumatically fractured anterior tooth with pulp exposure, describes their advantages and highlights the steps involved in their use. CASE PRESENTATION: A 14-year-old patient who came to our clinic with a traumatic crown fracture of the permanent, right central incisor is described. The patient had preserved the fragment that had broken off into his mouth and it was rebonded to the tooth using lasers (LightWalker device; Fotona, Ljubljana, Slovenia) with the following parameters: Er:YAG, SSP mode; 200 mJ; 10 Hz; quasi-contact tipless handpiece; Nd:YAG, SP mode; 4 W; 40 Hz; 300 MUm contact fiber. The whole procedure was performed without the need for anesthesia. CONCLUSIONS: The patient reported that he did not feel pain or discomfort throughout the intervention. Follow-up visits performed after one, three, six, twelve, and sixteen months demonstrated vitality of the tooth the absence of complications, as well as good esthetic results. Laser technology may be used in the treatment of traumatic anterior teeth injury with advantages in terms of quality of the restoration, esthetic results, and patient comfort. PMID- 26839855 TI - Cardiac Injuries: A Review of Multidetector Computed Tomography Findings. AB - Trauma is the leading cause of death in United States in the younger population. Cardiac trauma is common following blunt chest injuries and is associated with high morbidity and mortality. This study discusses various multidetector computed tomography (MDCT) findings of cardiac trauma. Cardiac injuries are broadly categorized into the most commonly occurring blunt cardiac injury and the less commonly occurring penetrating injury. Signs and symptoms of cardiac injury can be masked by the associated injuries. Each imaging modality including chest radiographs, echocardiography, magnetic resonance imaging and MDCT has role in evaluating these patients. However, MDCT is noninvasive; universally available and has a high spatial, contrast, and temporal resolution. It is a one stop shop to diagnose and evaluate complications of cardiac injury. MDCT is an imaging modality of choice to evaluate patients with cardiac injuries especially the injuries capable of causing hemodynamic instability. PMID- 26839858 TI - Treatment of Nonunion of Forearm Bones Using Radial Forearm Bone Flap. AB - BACKGROUND: Treatment of forearm fracture nonunion is challenging. Several surgical techniques for the treatment of forearm nonunion have been reported. OBJECTIVES: The aim of this prospective study was to evaluate the effects of the radial forearm bone graft technique in cases with forearm nonunion. PATIENTS AND METHODS: We treated 7 patients with forearm nonunions via radial forearm bone flap and internal plate fixation. On the preoperative examination and last follow up, the quick disabilities of the arm, shoulder, and hand (Q-DASH) score, elbow, forearm and wrist arches of motion and grip force were measured. At the final follow-up, radiographic union and patient satisfaction and return to work were assessed. RESULTS: The mean follow-up duration was 34 +/- 23 months. The Q-DASH scores improved from 70 +/- 6 points preoperatively to 13 +/- 15 points at final follow-up (P < 0.01). The preopetative range of motion (ROM) was 101 +/- 26 degrees; whereas the final forearm ROM was 140 +/- 17 (P = 0.01). All nonunions united uneventfully (range 3-6 months). At the last follow-up, the grip force was 83% of uninjured extremity and all patients were satisfied with the outcome of the operation. CONCLUSIONS: Radial forearm bone flap is a safe, useful and novel technique in cases with forearm nonunion. PMID- 26839859 TI - Association of Temperature and Humidity with Trauma Deaths. AB - BACKGROUND: Few studies worldwide have shown that climate factors such as temperature and humidity may contribute to injuries and sudden death. However, to the best of our knowledge no studies have been conducted on climate and traumatic deaths in Iran. OBJECTIVES: The aim of this study was to investigate the relationship between temperature and humidity and trauma deaths in Kerman, Iran. MATERIALS AND MATERIALS: In this study, data of all trauma deaths from March 2006 to February 2011 were collected from the Kerman Health Ministry and categorized by causes. Trauma deaths were extracted and matched with data regarding temperature and humidity obtained from the Kerman Meteorology Office during the same time period. Negative binomial regression and Spearman correlation analysis were used to analyze the data using STATA10 and MiniTab16. RESULTS: The findings of this study showed that the overall mortality caused by trauma is higher in the warm season. The highest correlation between mortality and temperature was seen in ages over 60 years (r = 0.301, P = 0.020) in trauma deaths and was statistically significant. An inverse significant correlation was observed between the incidence of trauma deaths and humidity and was highest in the over 60-year age group (r = -0.336, P = 0.009). The regression results also revealed an inverse significant relationship between humidity and trauma deaths in the over 60-year age group. CONCLUSIONS: High temperatures and low humidity increased the risk of trauma deaths in our study. However, more studies are needed to document this. PMID- 26839860 TI - Assessing the Physical Environment of Emergency Departments. AB - BACKGROUND: Emergency Department (ED) is considered to be the heart of a hospital. Based on many studies, a well-organized physical environment can enhance efficacy. OBJECTIVES: In this study, we aimed to investigate the influence of physical environment in EDs on efficacy. MATERIALS AND METHODS: This analytical cross-sectional study was conducted via the faculty members of the ED and residents of Shahid Beheshti University of Medical Sciences in Tehran, Iran. Data were collected using a predefined questionnaire. Descriptive statistics and ANOVA were used to analyze the data. RESULTS: Sixty-two participants, including 21 females and 41 males, completed the questionnaires. The mean age of the participants was 37 years (SD: 8.42). The mean work experience was 8 years (SD: 4.52) and all the studied variables varied within a range of 3.3 - 4.2. Time indices had the highest mean among variables followed by capacity, work space, treatment units, critical care units and, triage indices, respectively. CONCLUSIONS: In general, time indices including length of patient stay in the ED and space capacity, emphasizing the need to address these shortcomings. PMID- 26839861 TI - Serial Clinical Examinations of 100 Patients Treated for Anterior Abdominal Wall Stab Wounds: A Cross Sectional Study. AB - BACKGROUND: The current approach in stab wounds of the anterior abdominal wall is still unclear. OBJECTIVES: The goal of this study was to evaluate serial clinical examinations of patients with abdominal wall stab wounds referred to Poursina Hospital in Rasht. PATIENTS AND METHODS: In a cross sectional study, 100 cases with stab wounds to the anterior abdominal wall were examined serially (admission time, 4, 8, 12, and 24 hours) after wound exploration. Serial hemoglobin test was performed every 8 hours. Laparotomy was performed in cases who were not hemodynamically stable or who showed symptoms of peritonitis. The results were analyzed with SPSS software version 21. RESULTS: Ninety-one men (91%) and 9 women (9%) with mean age of 27 +/- 10.7 years were included. Coexisting injuries were prevalent in 12 cases. The duration of hospitalization was 1 day in 31%, 2 days in 30%, 3 - 4 days in 32% and more than 5 days in 7%. Late laparotomy was performed 12 hours after admission in 8% of patients due to peritonitis. There was visceral damage in these cases. No mortality occurred. The cost and duration of hospitalization was significantly higher in cases with coexisting injuries and those who underwent laparotomy. CONCLUSIONS: It seems serial clinical examinations are safe and decrease the cost and duration of hospitalization in stable patients with anterior abdominal wall stab wounds. PMID- 26839862 TI - Assessment Competency of Nurses in Biological Incidents. AB - BACKGROUND: There are two main areas within emergency care which focus on departmental and staff preparedness in biological incidents. Despite the importance, little is known about the nurse's preparedness in facing these events. OBJECTIVES: The aim of this study was to assess the effect of two teaching methods (multimedia instructional module versus lecture presentation) on nurse's competency in biological incidents. MATERIALS AND METHODS: In this quasi experimental study, 90 nurses were randomly divided into three groups (lecture presentation, multimedia- compact disk, and control). Data were collected by thirty-four multiple-choice questions for measuring knowledge, and a visual analogue scale graded 0 - 100 for assessing attitude. Data were analyzed using a paired t-test and one-way ANOVA with SPSS version 17.0. A P value less than 0.05 was considered as statistically significant. RESULTS: The results revealed no statistically significant difference in nurse's competency mean scores between the lecture and multimedia CDs groups. CONCLUSIONS: It is recommended to use multimedia CDs for in-service education of nurses. PMID- 26839863 TI - Obstructed Defecation Syndrome After Delivery Trauma. AB - BACKGROUND: Obstructed defecation syndrome (ODS) occurs in about 7% of adults; it seems that the etiology of pelvic floor disorders is multifactorial. Pregnancy and childbirth damage to the pelvic nerve and muscles are proposed causes for this condition. The precise role of vaginal delivery (VD) is not clearly defined, although in recent studies association of pelvic floor disorder with Operative vaginal delivery and episiotomy has been proposed. OBJECTIVES: In this prospective study, we assessed the outcome of stapled transanal rectal resection (STARR) in females with one of the two modes of delivery (VD or caesarean section (C/S). PATIENTS AND METHODS: We used Longo's ODS score for the assessment of the severity of pelvic floor malfunction. Stapled Trans Anal Rectal Resection (STARR) procedure was performed using two circular staplers. Follow-up was done 12 months after the discharge. To assess the role of episiotomy in patient with VD, we divided them into two subgroups; females who had VD with episiotomy (Vd + epi) and females who had VD alone. Data were analyzed using SPSS version 20 software. P values less than 0.05 were considered statistically significant. RESULTS: In 30 consecutive females undergoing STARR for the treatment of ODS, who enrolled in this prospective study, 19 (63.3%) had Vaginal Delivery VD and 11 (36.7%) had Cesarean Section (C/S). The ODS score before the surgery was higher in females who had C/S, although there was no significant difference between VD and C/S groups in terms of the percentage of the ODS score improvement after the STARR surgery. CONCLUSIONS: Higher ODS score in females who had C/S showed that C/S could not protect the pelvic organ from pregnancy and delivery trauma. It seems that episiotomy has a protective effect during VD; it can reduce the severity of trauma in pelvic organs during childbearing. PMID- 26839864 TI - Necessity of Telemedicine. PMID- 26839865 TI - Magnetic Resonance Therapy Improves Clinical Phenotype and EEG Alpha Power in Posttraumatic Stress Disorder. AB - BACKGROUND: Posttraumatic stress disorder (PTSD) is a disabling and prevalent psychiatric disorder with limited effective treatment options. In addition to the clinical features of the disease, pathologic changes in the electroencephalogram (EEG), including decreased alpha power, have been reported. OBJECTIVES: To determine if magnetic brain stimulation can induce normalization of EEG abnormalities and improve clinical symptoms in PTSD in a preliminary, open-label evaluation. MATERIALS AND METHODS: We reviewed prospectively-collected data on 21 veterans that were consecutively-treated for PTSD. Magnetic resonance therapy (MRT) was administered for two weeks at treatment frequencies based on frequency domain analysis of each patient's dominant alpha-band EEG frequencies and resting heart rate. Patients were evaluated on the PTSD checklist (PCL-M) and pre- and post-treatment EEGs before and after MRT. RESULTS: Of the 21 patients who initiated therapy, 16 completed treatment. Clinical improvements on the PCL-M were seen in these 16 patients, with an average pre-treatment score of 54.9 and post-treatment score of 31.8 (P < 0.001). In addition, relative global EEG alpha band (8 - 13 Hz) power increased from 32.0 to 38.5 percent (P = 0.013), and EEG delta-band (1 - 4 Hz) power decreased from 32.3 percent to 26.8 percent (P = 0.028). CONCLUSIONS: These open-label data show trends toward normalization of EEG and concomitant clinical improvement using magnetic stimulation for PTSD. PMID- 26839868 TI - Emergency Nurses' Requirements for Disaster Preparedness. AB - BACKGROUND: Natural and man-made disasters affect people, communities, and health systems. Nurses play a key role in the health system and must be prepared for appropriate response in disasters. OBJECTIVES: This study was done to assess the current knowledge of nurses in emergency departments for disaster preparedness. PATIENTS AND METHODS: This cross-sectional study was conducted on 110 emergency nurses working in teaching hospitals affiliated to Iran University of Medical Sciences, Tehran, Iran. A questionnaire was used to collect data and the data were then analyzed using descriptive and inferential statistics with SPSS software version 16.0. RESULTS: Based on the findings, most of the participants (64.5%) were aged 30 - 39 years old. 84% of the cases were female and 97.3% had a bachelor's degree. The average perceived knowledge of nurses was 2.43 +/- 1.01. The nurses had the highest familiarity with triage and lowest knowledge in epidemiology and decision-making. CONCLUSIONS: Lack knowledge of nurses regarding response to disaster situations indicates inefficiencies in the current system. Therefore, it is recommended to organize more workshops, annual training courses, and maneuvers based on staff needs and formulate continuous education courses for nurses. PMID- 26839867 TI - Reconstructive Surgery of Auricular Defects: An Overview. AB - CONTEXT: Despite the ongoing advances in surgical procedures and promising progress in bioengineering techniques, auricular reconstruction remains a significant challenge in plastic surgery. There are different causes for acquired auricular defects, including trauma, tumor ablation and burns. The management options for upper, middle and lower third auricular defects are briefly reviewed in the current paper. EVIDENCE ACQUISITION: Original research papers investigating the plastic surgeons, otolaryngologists and maxillofacial surgeons in approaching the complicated issue of auricular reconstruction published from January 1995 to December 2014 were aggregated and used in the current study. RESULTS: Utilizing autologous stem cell populations to treat craniofacial defects is a promising field of ongoing investigations. Studies show that cartilage stem/progenitor cells (CSPCs) are highly chondrogenic and can produce elastic reconstructive material with long-term tissue restoration. CONCLUSIONS: Auricular reconstruction surgery is a challenging plastic procedure that requires great expertise and expert knowledge of the various techniques available. Novel techniques in the fields of reconstructive bioengineering and regenerative medicine are promising but further research is required before widespread clinical application. PMID- 26839866 TI - The Advantages and Disadvantages of Methods Used to Control Liver Bleeding: A Review. AB - CONTEXT: Despite advancements in the science of surgery, minimizing bleeding from parenchymal tissue of the liver continues to be one of the challenges surgeons are facing to protect patients' lives. However, the number of surgeries needing incisions in the liver tissue, e.g. metastatectomy, is constantly increasing. EVIDENCE ACQUISITION: A MEDLINE and conventional search of the past 50 years of the medical literature was performed to identify relevant articles on hemostasis in the liver parenchymal tissue. RESULTS: The studies that have been published on hemostasis in the liver parenchymal tissue can be classified into 3 categories: 1. surgical procedures; 2. methods affecting body hemodynamic; 3. pharmacological methods. The purpose of these studies are to identify the best therapeutic approaches that not only minimize the bleeding, but also save the maximum amount of the liver tissue and minimize the use of partial liver resections. CONCLUSIONS: The excessive blood loss and the long time needed to control the bleeding during liver surgery impose several side effects and complications on patients. Topical hemostatic agents such as ferric chloride, potassium aluminum sulfate (alum) and aluminum chloride are safely applicable in patients. These agents might be used along with other current methods to minimize the blood loss and the need for blood products during liver surgeries. PMID- 26839869 TI - Assessment of Vascular Injuries and Reconstruction. AB - BACKGROUND: Trauma is the third leading cause of death. In this regard, vascular injury plays a leading role in of morbidity and mortality rates. OBJECTIVES: The present study aimed to assess the prevalence of vascular injuries and results of vascular reconstruction at a referral hospital in northern Iran. PATIENTS AND METHODS: A retrospective observational study assessed 88 consecutive patients with vascular injury admitted to Poursina Hospital, Rasht in northern Iran, from October 2007 to October 2009. All study information was collected retrospectively from hospital charts. RESULTS: Most of the affected patients (87/88) were male with a mean age of 29.12 +/- 11.20 years. The mechanism of injury in 39.8% was blunt trauma and penetrating trauma in the rest. Of the 53 injured by penetrating trauma (60.2%), the most common cause was stabbing (94.3%). The most common cause of blunt trauma was road traffic accidents (93.1%). The most common mechanism for vascular injuries in upper extremities was penetrating trauma (86.0%) and in lower extremities was blunt trauma (60.0%). Fasciotomy was performed in 16 patients (18.2%) mostly in the lower extremities. Major amputation was required in 10% of the patients. In upper extremities, the most common type of revascularization was end to end anastomosis, followed by inter-position graft. The most common type of reconstruction in the lower extremity was bypass graft. All patients who underwent major amputation were admitted to the center with a delay of more than 6 hours after injury. CONCLUSIONS: Major vascular injuries in our center occurred in young men, frequently because of stab wounds. Popliteal injuries mostly caused by motor vehicle accidents was the second most common arterial injury, followed by combined ulnar and radial injuries. Vascular reconstruction in the first hours after trauma may prevent many unnecessary and preventable amputation procedures. PMID- 26839870 TI - National Getaways for the Weary Trauma Surgeon; Part 5: Shiraz, the City of Gardens and Hospitality. PMID- 26839871 TI - Low Salt Diet and Insulin Resistance. AB - It is well known that high sodium intake is closely associated with the risk of cardiovascular disease, but the effect of low sodium intake on insulin resistance is not clear. In this article, we summarize findings from previous studies focusing on the association between low sodium intake and insulin resistance. While many investigations on this topic have been conducted actively, their major findings are inconsistent, partly due to different study designs. Thus, additional randomized controlled trials with an adequate study period and reasonable levels of low sodium intake are needed. PMID- 26839872 TI - Leukocyte Telomere Length is Associated With Serum Vitamin B12 and Homocysteine Levels in Older Adults With the Presence of Systemic Inflammation. AB - Folate, vitamin B12, and homocysteine (HCY) are involved in the metabolism of nucleic acid precursors and it has been hypothesized that they also influence telomere length, a biomarker of aging. However, previous studies have reported inconsistent findings, and data for older adults are limited. Our study aimed to evaluate associations between leukocyte telomere length (LTL) and serum folate, vitamin B12, and HCY levels among adults aged 55 years and over. In a cross sectional study in 798 men and women aged 55-79 years, serum folate, vitamin B12, and HCY levels were measured using chemiluminescent immunometric assays, and relative LTL was assessed using quantitative real-time polymerase chain reaction. To evaluate associations between LTL and serum folate, vitamin B12, and HCY levels, multiple linear regression models were used. In multiple models adjusted for age, sex, serum high sensitive C-reactive protein (hs-CRP) levels, and other potential confounding factors, we found no association between LTL and serum folate, vitamin B12, and HCY levels. However, we did find a significant inverse association between HCY levels and LTL in participants with serum hs-CRP levels of >= 2 mg/L (p < 0.05). Moreover, there was a trend toward an association between HCY and vitamin B12 levels in these individuals (p = 0.08). In those with serum hs-CRP levels of < 2 mg/L, HCY was inversely associated with vitamin B12 levels (p < 0.001) and had no association with LTL. Our findings suggest that increased serum HCY levels, when combined with the presence of systemic inflammation, may play a role in accelerating biological aging. PMID- 26839873 TI - Association of Maternal Diet With Zinc, Copper, and Iron Concentrations in Transitional Human Milk Produced by Korean Mothers. AB - The aims of this study were to evaluate zinc, copper, and iron concentrations in the transitory milk of Korean lactating mothers and to investigate the relationship between these concentrations and maternal diet. Human milk samples were collected between 5 and 15 days postpartum from 96 healthy, lactating mothers in postpartum care centers in Seoul, Korea. Dietary intake during lactation was determined based on a 3-day dietary record. The mean zinc, copper, and iron concentrations in the human milk samples collected were 3.88 +/- 1.74 mg/L, 0.69 +/- 0.25 mg/L, and 5.85 +/- 8.53 mg/L, respectively. The mothers who consumed alcoholic beverages during pregnancy had tended to have lower concentrations of zinc and copper, as well as significantly lower concentrations of iron, in their milk (p < 0.047). In contrast, the mothers who took daily supplements had much higher iron concentrations in their milk (p = 0.002). Dietary intakes of zinc, copper, and iron during lactation did not affect the concentrations of zinc, copper, and iron in the milk samples analyzed. Intakes of vitamin C, selenium, and iodine were associated with the concentration of copper in the milk samples analyzed, and consumption of food categorized as 'meat and meat products' was positively associated with the concentration of zinc. Consumption of rice was the top contributor to the concentrations of all three minerals. In conclusion, associations between maternal diet and nutrient concentrations in transitory human milk can provide useful information, particularly in regard to infant growth. PMID- 26839874 TI - Effect of A One-Week Balanced Diet on Expression of Genes Related to Zinc Metabolism and Inflammation in Type 2 Diabetic Patients. AB - To evaluate the effect of diet on metabolic control and zinc metabolism in patients with type 2 diabetes mellitus (T2DM). One-week balanced diet was provided to 10 Brazilians patients with T2DM. Nutritional assessment, laboratorial parameters and expression of zinc transporter and inflammatory genes in peripheral blood mononuclear cells (PBMC) were performed. Healthy non-diabetic subjects of the same demographic were recruited to provide baseline data. Diabetic patients had higher body mass index and greater fasting plasma glucose, plasma tumor necrosis factor alpha (TNFalpha) and plasma interleukin 6 (IL6) levels compared with healthy subjects. In addition, the expression of transporters 4 (ZnT4) mRNA was lower and IL6 mRNA was higher in PBMC of these diabetic patients than in healthy subject. One week after a balanced diet was provided, fasting plasma glucose decreased significantly as did TNFalpha, IL6 and Metallothionein 1 (MT1) mRNAs. No change was observed in zinc transporter expression in PBMC after the dietary intervention. A healthy eating pattern maintained for one week was able to improve metabolic control of diabetic patients by lowering fasting plasma glucose. This metabolic control may be related to down-regulation of zinc-related transcripts from PBMCs, as TNFalpha, IL6 and MT1 mRNA. PMID- 26839875 TI - Fasting Glucose is a Useful Indicator for Cerebrovascular Risk in Non-Diabetic Koreans: Association With Oxidative Stress and Inflammation. AB - Diabetes and impaired fasting glucose are associated with incidence of cerebro /cardio-vascular diseases. This study hypothesized that fasting glycemic status may reflect cerebrovascular risk in non-diabetic Koreans. Fasting glycemic status, lipid profiles, oxidative stress, and inflammation markers were measured in non-diabetic subjects (healthy controls, n = 112 and stroke n = 41). Systolic blood pressure, fasting glucose, glycated hemoglobin (HbA1C), triglycerides, high sensitivity C-reactive protein (hs-CPR), interleukin-6, and tumor necrosis factor alpha were higher, and high density lipoprotein (HDL)-cholesterols were lower in patients with stroke than healthy controls. Fasting glucose positively correlated with hs-CRP, interleukin-6, tumor necrosis factor-alpha, oxidized low density lipoprotein (LDL) and malondialdehyde. The significances continued or at least turned to a trend after adjustments for confounding factors. Multiple regression analyses revealed that fasting glucose was mainly associated with cerebrovascular risk (beta'-coefficient = 0.284, p < 0.0001) together with age, systolic blood pressure, total cholesterol, hs-CRP, body mass index, dietary poly unsaturated fatty acid/saturated fatty acid (PUFA/SFA), and HbA1C (r(2) = 0.634, p = 0.044). The subjects were subdivided by their fasting glucose levels [normal fasting glucose: 70-99 mg/dL, n = 91 [NFG-control] and n = 27 [NFG-stroke]; higher fasting glucose: 100-125 mg/dL, n = 21 [HFG-control] and n = 14 [HFG-stroke]). In both controls and stroke patients, HFG groups show higher triglyceride, total- and LDL-cholesterol and lower HDL-cholesterol than NFG groups. Control-HFG group showed significantly higher levels of oxidative stress and inflammation than control-NFG group. Stroke-HFG group also showed significantly higher inflammatory levels than stroke-NFG group, moreover the highest among the groups. Additionally, stroke-NFG group consumed higher PUFA/SFA than stroke-HFG group. Fasting glucose may be a useful indicator for cerebrovascular risk in non diabetic individuals which may be mediated by oxidative stress and inflammation status. PMID- 26839876 TI - Nutritional Status and Body Composition in Korean Myopathy Patients. AB - In myopathy patients, fat mass increases as the disease progresses, while lean body mass decreases. The present study aimed to investigate the overall nutritional status of Korean myopathy patients through surveys of diet and dietary habits, bioelectrical impedance analysis (BIA), and biochemistry tests, as well as the examination of related factors, for the purpose of using such findings as a basis for improving the nutritional status in myopathy patients. The energy intake of all participants was found to be insufficient at only 44.5% of Dietary Reference Intakes for Koreans 2010 (KDRIs 2010), whereas protein intake was sufficient at 89.8% of KDRIs 2010. Dietary fiber intake was found to be 58.4% of sufficient dietary fiber intake for adults according to KDRIs 2010. Calcium intake was found to be 55.0% and magnesium was 14.9% of the recommended calcium and magnesium intake for adults according to KDRIs 2010. With respect to quality of life (QOL), overall increase in QOL domain score showed significant positive correlations with vegetable fat intake (p < 0.05), vegetable protein intake (p < 0.05), and dietary fiber intake (p < 0.05). With respect to BIA, the mean phage angle of all participants was found to be 2.49 +/- 0.93 degrees , which was below the cutoff value. As a study that examined nutrient analysis and dietary habits of myopathy patients in Korea, the present study is meaningful in providing the basic data for future studies that aim to present dietary guidelines for patients suffering from myopathy. PMID- 26839877 TI - Effect of Salivary Reaction Time on Flow Properties of Commercial Food Thickeners Used for Dysphagic Patients. AB - The effect of human saliva on the flow properties of pudding-like thickened water prepared with commercial food thickeners was investigated, and their viscosity differences were also compared as a function of salivary reaction time (0-60 min after the addition of saliva). Food thickeners used in this study were starch based (SB), gum-containing starch-based (GSB), and gumbased (GB) commercial thickeners marketed in Korea. GB showed no significant reduction in viscosity upon contact with human saliva during the salivary reaction. In contrast, SB almost completely lost its viscosity shortly after the addition of saliva, and GSB significantly reduced its viscosity after 20 min of reaction time but retained its viscosity. The results of this study indicate that GB can enhance the swallowing safety of dysphagic patients by retaining a stable viscosity level without the reduction of viscosity during consumption of thickened fluids, whereas SB may increase the possibility of aspiration owing to a rapid decrease of viscosity upon contact with human saliva. PMID- 26839878 TI - Ketogenic Diet for Children with Epilepsy: A Practical Meal Plan in a Hospital. AB - A ketogenic diet (KD) is a dietary approach to treat intractable epilepsy. The KD begins with hospitalization and the child and their parents can adapt to the KD for 1-2 weeks. Recently, various type of dietary intervention such as the modified Atkins diet (MAD) and the low glycemic index treatment (LGIT) have been performed. Since 2010, we carried out the KD, MAD, and LGIT for total of 802 patients; 489 patients (61%) for the KD, 147 patients (18.3%) with the MAD, and 166 patients (20.7%) for the LGIT. In this report, application of these dietary practices in Severance Hospital is shared. PMID- 26839879 TI - Interdisciplinary Medication Adherence Program: The Example of a University Community Pharmacy in Switzerland. AB - The Community Pharmacy of the Department of Ambulatory Care and Community Medicine (Policlinique Medicale Universitaire, PMU), University of Lausanne, developed and implemented an interdisciplinary medication adherence program. The program aims to support and reinforce medication adherence through a multifactorial and interdisciplinary intervention. Motivational interviewing is combined with medication adherence electronic monitors (MEMS, Aardex MWV) and a report to patient, physician, nurse, and other pharmacists. This program has become a routine activity and was extended for use with all chronic diseases. From 2004 to 2014, there were 819 patient inclusions, and 268 patients were in follow-up in 2014. This paper aims to present the organization and program's context, statistical data, published research, and future perspectives. PMID- 26839880 TI - Optimal Experiment Design for Monoexponential Model Fitting: Application to Apparent Diffusion Coefficient Imaging. AB - The monoexponential model is widely used in quantitative biomedical imaging. Notable applications include apparent diffusion coefficient (ADC) imaging and pharmacokinetics. The application of ADC imaging to the detection of malignant tissue has in turn prompted several studies concerning optimal experiment design for monoexponential model fitting. In this paper, we propose a new experiment design method that is based on minimizing the determinant of the covariance matrix of the estimated parameters (D-optimal design). In contrast to previous methods, D-optimal design is independent of the imaged quantities. Applying this method to ADC imaging, we demonstrate its steady performance for the whole range of input variables (imaged parameters, number of measurements, and range of b values). Using Monte Carlo simulations we show that the D-optimal design outperforms existing experiment design methods in terms of accuracy and precision of the estimated parameters. PMID- 26839881 TI - Species Specificity of the Putative Male Antennal Aphrodisiac Pheromone in Leptopilina heterotoma, Leptopilina boulardi, and Leptopilina victoriae. AB - Male antennal aphrodisiac pheromones have been suggested to elicit female receptiveness in several parasitic Hymenoptera, including Leptopilina boulardi. None of the proposed pheromones, however, has been fully identified to date. It is also unknown whether these antennal pheromones are species specific, because the species specificity of mate recognition and courtship elicitation in Leptopilina prevented such experiments. In this study we present an experimental design that allows the investigation of the species specificity of the putative male aphrodisiac pheromone of L. heterotoma, L. boulardi, and L. victoriae. This is achieved by chemical manipulation of the odour profile of heterospecific females, so that males perceive them as conspecifics and show antennal courtship behaviour. Males courted the manipulated heterospecific females and antennal contact between the male and the female was observed. However, males elicited receptiveness only in conspecific females, never in the manipulated heterospecific females. Chemical analysis showed the presence of species specific unsaturated hydrocarbons on the antennae of males. Only trace amounts of these hydrocarbons are found on the antennae of females. Our results are an important step towards the understanding and identification of antennal pheromones of parasitic wasps. PMID- 26839882 TI - Downregulation of Heparanase Expression Results in Suppression of Invasion, Migration, and Adhesion Abilities of Hepatocellular Carcinoma Cells. AB - OBJECTIVE: Heparanase (HPSE) is high-expressed in most malignant tumors including hepatocellular carcinoma (HCC) and promotes cancer cell invasion and migration. The aim of the study is to explore whether HPSE enhances adhesion in metastasis of HCC cells. METHODS: HPSE expressions in human HCC cells were measured with real-time RT-PCR and Western blot analysis. Four recombinant miRNA vectors pcDNATM6.2-GW/EmGFP-miR-HPSE (pmiR-HPSE) were transfected into HCCLM3 cell. HPSE expression in transfected cell was measured. The cell invasion, migration, and adhesion abilities were detected, respectively. RESULTS: Both HPSE mRNA and protein relative expression levels were higher in HepG2, BEL-7402, and HCCLM3 cells than those in normal hepatocyte (P < 0.05). HPSE showed highest expression level in HCCLM3 cell (P < 0.05). Transfection efficiencies of four miRNA vectors were 75%-85%. The recombinant vectors significantly decreased HPSE expression in transfected HCCLM3 cells (P < 0.01), and pmiR-HPSE-1 showed best interference effect (P < 0.05). pmiR-HPSE-1 significantly decreased the penetrated and migrating cells numbers and adherence rate of HCCLM3 cells (P < 0.05). CONCLUSION: HPSE is a potentiator of cell adhesion in metastasis of HCC. PMID- 26839883 TI - Outcomes of Intracytoplasmic Sperm Injection Cycles for Complete Teratozoospermia: A Case-Control Study Using Paired Sibling Oocytes. AB - OBJECTIVE: To investigate the outcomes of intracytoplasmic sperm injection (ICSI) cycles where sibling oocytes from a single donor were split between two recipients based on strict sperm morphology. METHODS: Retrospective cohort study. All ICSI cycles had one donor's oocytes split between two recipients in a 1 : 1 ratio based on strict sperm morphology, that is, one male partner had morphology of 0% and the other had morphology of >1%. Fertilization, positive hCG, clinical pregnancy, spontaneous miscarriage, and live birth rates of the aforementioned groups were compared. RESULTS: The baseline characteristics of the two groups (n = 103), including semen parameters of the male partners, were comparable. There was no difference in the fertilization rates when comparing the 0% group to the >1% group (78.7% versus 81.6%; P = 0.66). The overall positive hCG, clinical pregnancy, spontaneous miscarriage, and live birth rates for the 0% group were 61.2%, 49.5%, 10.7%, and 38.8%, respectively. The corresponding rates in the >1% group were positive hCG (63.1%), clinical pregnancy (55.3%), spontaneous miscarriage (7.77%), and live birth (46.6%). CONCLUSIONS: The fertilization and pregnancy outcomes of ICSI cycles for strict sperm morphology of 0% versus morphology of >1% are equivalent. These results can provide reassurance to couples undergoing ICSI for severe teratospermia. PMID- 26839884 TI - Predicting Long Noncoding RNA and Protein Interactions Using Heterogeneous Network Model. AB - Recent study shows that long noncoding RNAs (lncRNAs) are participating in diverse biological processes and complex diseases. However, at present the functions of lncRNAs are still rarely known. In this study, we propose a network based computational method, which is called lncRNA-protein interaction prediction based on Heterogeneous Network Model (LPIHN), to predict the potential lncRNA protein interactions. First, we construct a heterogeneous network by integrating the lncRNA-lncRNA similarity network, lncRNA-protein interaction network, and protein-protein interaction (PPI) network. Then, a random walk with restart is implemented on the heterogeneous network to infer novel lncRNA-protein interactions. The leave-one-out cross validation test shows that our approach can achieve an AUC value of 96.0%. Some lncRNA-protein interactions predicted by our method have been confirmed in recent research or database, indicating the efficiency of LPIHN to predict novel lncRNA-protein interactions. PMID- 26839885 TI - Evaluation of the Relationship between the NRT-Ratio, Cochlear Anatomy, and Insertions Depth of Perimodiolar Cochlear Implant Electrodes. AB - The position of the cochlear implant electrode array within the scala tympani is essential for an optimal postoperative hearing benefit. If the electrode array changes in between the scalae intracochlearly (i.e., from scala tympani to scala vestibuli), a reduced auditory performance can be assumed. We established a neural response telemetry-ratio (NRT-ratio) which corresponds with the scalar position of the electrodes but shows within its limits a variability. The aim of this study was to determine if insertion depth angle or cochlea size influences the NRT-ratio. The intraoperative electrophysiological NRT data of 26 patients were evaluated. Using a flat panel tomography system, the position of the electrode array was evaluated radiologically. The insertion depth angle of the electrode, the cochlea size, and the NRT-ratio were calculated postoperatively. The radiological results were compared with the intraoperatively obtained electrophysiological data (NRT-ratio) and statistically evaluated. In all patients the NRT-ratio, the insertion depth angle, and the cochlea size could be determined. A significant correlation between insertional depth, cochlear size, and the NRT-ratio was not found. The NRT-ratio is a reliable electrophysiological tool to determine the scalar position of a perimodiolar electrode array. The NRT ratio can be applied independent from insertion depth and cochlear size. PMID- 26839886 TI - SimFuse: A Novel Fusion Simulator for RNA Sequencing (RNA-Seq) Data. AB - The performance evaluation of fusion detection algorithms from high-throughput sequencing data crucially relies on the availability of data with known positive and negative cases of gene rearrangements. The use of simulated data circumvents some shortcomings of real data by generation of an unlimited number of true and false positive events, and the consequent robust estimation of accuracy measures, such as precision and recall. Although a few simulated fusion datasets from RNA Sequencing (RNA-Seq) are available, they are of limited sample size. This makes it difficult to systematically evaluate the performance of RNA-Seq based fusion detection algorithms. Here, we present SimFuse to address this problem. SimFuse utilizes real sequencing data as the fusions' background to closely approximate the distribution of reads from a real sequencing library and uses a reference genome as the template from which to simulate fusions' supporting reads. To assess the supporting read-specific performance, SimFuse generates multiple datasets with various numbers of fusion supporting reads. Compared to an extant simulated dataset, SimFuse gives users control over the supporting read features and the sample size of the simulated library, based on which the performance metrics needed for the validation and comparison of alternative fusion-detection algorithms can be rigorously estimated. PMID- 26839887 TI - Long Read Alignment with Parallel MapReduce Cloud Platform. AB - Genomic sequence alignment is an important technique to decode genome sequences in bioinformatics. Next-Generation Sequencing technologies produce genomic data of longer reads. Cloud platforms are adopted to address the problems arising from storage and analysis of large genomic data. Existing genes sequencing tools for cloud platforms predominantly consider short read gene sequences and adopt the Hadoop MapReduce framework for computation. However, serial execution of map and reduce phases is a problem in such systems. Therefore, in this paper, we introduce Burrows-Wheeler Aligner's Smith-Waterman Alignment on Parallel MapReduce (BWASW-PMR) cloud platform for long sequence alignment. The proposed cloud platform adopts a widely accepted and accurate BWA-SW algorithm for long sequence alignment. A custom MapReduce platform is developed to overcome the drawbacks of the Hadoop framework. A parallel execution strategy of the MapReduce phases and optimization of Smith-Waterman algorithm are considered. Performance evaluation results exhibit an average speed-up of 6.7 considering BWASW-PMR compared with the state-of-the-art Bwasw-Cloud. An average reduction of 30% in the map phase makespan is reported across all experiments comparing BWASW-PMR with Bwasw-Cloud. Optimization of Smith-Waterman results in reducing the execution time by 91.8%. The experimental study proves the efficiency of BWASW PMR for aligning long genomic sequences on cloud platforms. PMID- 26839888 TI - New Derivatives of Pyridoxine Exhibit High Antibacterial Activity against Biofilm Embedded Staphylococcus Cells. AB - Opportunistic bacteria Staphylococcus aureus and Staphylococcus epidermidis often form rigid biofilms on tissues and inorganic surfaces. In the biofilm bacterial cells are embedded in a self-produced polysaccharide matrix and thereby are inaccessible to biocides, antibiotics, or host immune system. Here we show the antibacterial activity of newly synthesized cationic biocides, the quaternary ammonium, and bisphosphonium salts of pyridoxine (vitamin B6) against biofilm embedded Staphylococci. The derivatives of 6-hydroxymethylpyridoxine were ineffective against biofilm-embedded S. aureus and S. epidermidis at concentrations up to 64 MUg/mL, although all compounds tested exhibited low MICs (2 MUg/mL) against planktonic cells. In contrast, the quaternary ammonium salt of pyridoxine (N,N-dimethyl-N-((2,2,8-trimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5 yl)methyl)octadecan-1-aminium chloride (3)) demonstrated high biocidal activity against both planktonic and biofilm-embedded bacteria. Thus, the complete death of biofilm-embedded S. aureus and S. epidermidis cells was obtained at concentrations of 64 and 16 MUg/mL, respectively. We suggest that the quaternary ammonium salts of pyridoxine are perspective to design new synthetic antibiotics and disinfectants for external application against biofilm-embedded cells. PMID- 26839889 TI - Blood Glucose Fluctuations in Type 2 Diabetes Patients Treated with Multiple Daily Injections. AB - To compare blood glucose fluctuations in type 2 diabetes mellitus (T2DM) patients were treated using three procedures: insulin intensive therapy which is continuous subcutaneous insulin infusion (CSII), MDI3 (three injections daily), and MDI4 (four injections daily). T2DM patients were hospitalized and were randomly assigned to CSII, aspart 30-based MDI3, and glargine based MDI4. Treatments were maintained for 2-3 weeks after the glycaemic target was reached. After completing the baseline assessment, 6-day continuous glucose monitoring (CGM) was performed before and after completion of insulin treatment. Treatment with CSII provided a greater improvement of blood glucose fluctuations than MDI (MDI3 or MDI4) therapy either in newly diagnosed or in long-standing T2DM patients. In long-standing diabetes patients, the MDI4 treatment group had significantly greater improvement of mean amplitude glycemic excursion (MAGE) than the MDI3 treatment group. However, in patients with newly diagnosed diabetes, there were no significant differences in the improvement of MAGE between MDI3 and MDI4 groups. Glargine based MDI4 therapy provided better glucose fluctuations than aspart 30-based MDI3 therapy, especially in long-standing T2DM patients, if CSII therapy was not available. PMID- 26839890 TI - Mechanism Investigation of the Improvement of Chang Run Tong on the Colonic Remodeling in Streptozotocin-Induced Diabetic Rats. AB - Previous study demonstrated that Chang Run Tong (CRT) could partly restore the colon remodeling in streptozotocin- (STZ-) induced diabetic rats. Here we investigated the mechanisms of such effects of CRT. Diabetes was induced by a single injection of 40 mg/kg of STZ. CRT was poured into the stomach by gastric lavage once daily for 60 days. The remodeling parameters were obtained from diabetic (DM), CRT treated diabetic (T1, 50 g/kg; T2, 25 g/kg), and normal (Con) rats. Expressions of advanced glycation end product (AGE), AGE receptor, transforming growth factor-beta1 (TGF-beta1), and TGF-beta1 receptor in the colon wall were immunochemically detected and quantitatively analyzed. The association between the expressions of those proteins and the remodeling parameters was analyzed. The expressions of those proteins were significantly higher in different colon layers in the DM group (P < 0.05, P < 0.01) and highly correlated to the remodeling parameters. Furthermore, the expressions of those proteins were significantly decreased in the T1 group (P < 0.05, P < 0.01) but not in the T2 group (P > 0.05). The corrective effect on the expressions of those proteins is likely to be one molecular pathway for the improvement of CRT on the diabetes induced colon remodeling. PMID- 26839891 TI - Subclinical Alterations of Cardiac Mechanics Present Early in the Course of Pediatric Type 1 Diabetes Mellitus: A Prospective Blinded Speckle Tracking Stress Echocardiography Study. AB - Diabetic cardiomyopathy substantially accounts for mortality in diabetes mellitus. The pathophysiological mechanism underlying diabetes-associated nonischemic heart failure is poorly understood and clinical data on myocardial mechanics in early stages of diabetes are lacking. In this study we utilize speckle tracking echocardiography combined with physical stress testing in order to evaluate whether left ventricular (LV) myocardial performance is altered early in the course of uncomplicated type 1 diabetes mellitus (T1DM). 40 consecutive asymptomatic normotensive children and adolescents with T1DM (mean age 11.5 +/- 3.1 years and mean disease duration 4.3 +/- 3.5 years) and 44 age- and gender matched healthy controls were assessed using conventional and quantitative echocardiography (strain and strain rate) during bicycle ergometer stress testing. Strikingly, T1DM patients had increased LV longitudinal (p = 0.019) and circumferential (p = 0.016) strain rate both at rest and during exercise (p = 0.021). This was more pronounced in T1DM patients with a longer disease duration (p = 0.038). T1DM patients with serum HbA1c > 9% showed impaired longitudinal (p = 0.008) and circumferential strain (p = 0.005) and a reduced E/A-ratio (p = 0.018). In conclusion, asymptomatic T1DM patients have signs of hyperdynamic LV contractility early in the course of the disease. Moreover, poor glycemic control is associated with early subclinical LV systolic and diastolic impairment. PMID- 26839892 TI - Influence of Acute High Glucose on Protein Abundance Changes in Murine Glomerular Mesangial Cells. AB - The effects of acute exposure to high glucose levels as experienced by glomerular mesangial cells in postprandial conditions and states such as in prediabetes were investigated using proteomic methods. Two-dimensional gel electrophoresis and matrix assisted laser desorption ionization time of flight mass spectrometry methods were used to identify protein expression patterns in immortalized rat mesangial cells altered by 2 h high glucose (HG) growth conditions as compared to isoosmotic/normal glucose control (NG(*)) conditions. Unique protein expression changes at 2 h HG treatment were measured for 51 protein spots. These proteins could be broadly grouped into two categories: (1) proteins involved in cell survival/cell signaling and (2) proteins involved in stress response. Immunoblot experiments for a protein belonging to both categories, prohibitin (PHB), supported a trend for increased total expression as well as significant increases in an acidic PHB isoform. Additional studies confirmed the regulation of proteasomal subunit alpha-type 2 and the endoplasmic reticulum chaperone and oxidoreductase PDI (protein disulfide isomerase), suggesting altered ER protein folding capacity and proteasomal function in response to acute HG. We conclude that short term high glucose induces subtle changes in protein abundances suggesting posttranslational modifications and regulation of pathways involved in proteostasis. PMID- 26839893 TI - Effects of the New Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m on High Glucose Induced Prolongation of Cardiac QT Interval and Increase of Coronary Perfusion Pressure. AB - This study investigated the effects of the new aldose reductase inhibitor benzofuroxane derivative 5(6)-(benzo[d]thiazol-2-ylmethoxy)benzofuroxane (BF-5m) on the prolongation of cardiac QT interval and increase of coronary perfusion pressure (CPP) in isolated, high glucose (33.3 mM D-glucose) perfused rat hearts. BF-5m was dissolved in the Krebs solution at a final concentration of 0.01 MUM, 0.05 MUM, and 0.1 MUM. 33.3 mM D-glucose caused a prolongation of the QT interval and increase of CPP up to values of 190 +/- 12 ms and 110 +/- 8 mmHg with respect to the values of hearts perfused with standard Krebs solution (11.1 mM D glucose). The QT prolongation was reduced by 10%, 32%, and 41%, respectively, for the concentration of BF-5m 0.01 MUM, 0.05 MUM, and 0.1 MUM. Similarly, the CPP was reduced by 20% for BF-5m 0.05 MUM and by 32% for BF-5m 0.1 MUM. BF-5m also increased the expression levels of sirtuin 1, MnSOD, eNOS, and FOXO-1, into the heart. The beneficial actions of BF-5m were partly abolished by the pretreatment of the rats with the inhibitor of the sirtuin 1 activity EX527 (10 mg/kg/day/7 days i.p.) prior to perfusion of the hearts with high glucose + BF-5m (0.1 MUM). Therefore, BF-5m supplies cardioprotection from the high glucose induced QT prolongation and increase of CPP. PMID- 26839894 TI - Comparison of Clinical Trajectories before Initiation of Renal Replacement Therapy between Diabetic Nephropathy and Nephrosclerosis on the KDIGO Guidelines Heat Map. AB - This study investigated differences between the clinical trajectories of diabetic nephropathy and nephrosclerosis using the Kidney Disease: Improving Global Outcomes (KDIGO) heat map and the clinical characteristics between the two diseases at RRT initiation. This single-center, retrospective study enrolled 100 patients whose estimated glomerular filtration rate (eGFR) was >=45 mL/min/1.73 m(2) at their first visit and who were initiated on RRT. Fifty consecutive patients were assigned to each of the diabetic nephropathy and nephrosclerosis groups. All data for simultaneously measured eGFR and urinary albumin to creatinine ratio (UACR) were collected from first visit to RRT initiation and were plotted on the KDIGO heat map. Diabetic nephropathy was characterized by higher blood pressure and UACR and lower age, eGFR, and serum albumin levels compared with nephrosclerosis at RRT initiation. The vast majority of patients with diabetic nephropathy and eGFR < 60 mL/min/1.73 m(2) had concomitant macroalbuminuria, whereas for patients with nephrosclerosis, even when eGFR was <45 mL/min/1.73 m(2), many still had normoalbuminuria or microalbuminuria. The rate of decline of eGFR was significantly faster in the diabetic nephropathy group than that in the nephrosclerosis group. The clinical trajectories of diabetic nephropathy and nephrosclerosis differed markedly on the KDIGO heat map. PMID- 26839895 TI - CCL2 Serum Levels and Adiposity Are Associated with the Polymorphic Phenotypes 2518A on CCL2 and 64ILE on CCR2 in a Mexican Population with Insulin Resistance. AB - Genetic susceptibility has been described in insulin resistance (IR). Chemokine (C-C motif) ligand-2 (CCL2) is overexpressed in white adipose tissue and is the ligand of C-C motif receptor-2 (CCR2). The CCL2 G-2518A polymorphism is known to regulate gene expression, whereas the physiological effects of the CCR2Val64Ile polymorphism are unknown. The aim of the study is to investigate the relationship between these polymorphisms with soluble CCL2 levels (sCCL2), metabolic markers, and adiposity. In a cross-sectional study we included 380 Mexican-Mestizo individuals, classified with IR according to Stern criteria. Polymorphism was identified using PCR-RFLP/sequence-specific primers. Anthropometrics and metabolic markers were measured by routine methods and adipokines and sCCL2 by ELISA. The CCL2 polymorphism was associated with IR (polymorphic A+ phenotype frequencies were 70.9%, 82.6%, in individuals with and without IR, resp.). Phenotype carriers CCL2 (A+) displayed lower body mass and fat indexes, insulin and HOMA-IR, and higher adiponectin levels. Individuals with IR presented higher sCCL2 compared to individuals without IR and was associated with CCR2 (Ile+) phenotype. The double-polymorphic phenotype carriers (A+/Ile+) exhibited higher sCCL2 than double-wild-type phenotype carriers (A-/Ile-). The present findings suggest that sCCL2 production possibly will be associated with the adiposity and polymorphic phenotypes of CCL2 and CCR2, in Mexican-Mestizos with IR. PMID- 26839896 TI - Genetic Analysis and Follow-Up of 25 Neonatal Diabetes Mellitus Patients in China. AB - AIMS: To study the clinical features, genetic etiology, and the correlation between phenotype and genotype of neonatal diabetes mellitus (NDM) in Chinese patients. METHODS: We reviewed the medical records of 25 NDM patients along with their follow-up details. Molecular genetic analysis was performed. We compared the HbA1c levels between PNDM group and infantile-onset T1DM patients. RESULTS: Of 25 NDM patients, 18 (72.0%) were PNDM and 7 (28.0%) were TNDM. Among 18 PNDM cases, 6 (33.3%) had known KATP channel mutations (KATP-PNDM). There were six non KATP mutations, five novel mutations, including INS, EIF2AK3 (n = 2), GLIS3, and SLC19A2, one known EIF2AK3 mutation. There are two ABCC8 mutations in TNDM cases and one paternal UPD6q24. Five of the six KATP-PNDM patients were tried for glyburide transition, and 3 were successfully switched to glyburide. Mean HbA1c of PNDM was not significantly different from infantile onset T1DM (7.2% versus 7.4%, P = 0.41). CONCLUSION: PNDM accounted for 72% of NDM patients. About one third of PNDM and TNDM patients had KATP mutations. The genetic etiology could be determined in 50% of PNDM and 43% of TNDM cases. PNDM patients achieved good glycemic control with insulin or glyburide therapy. The etiology of NDM suggests polygenic inheritance. PMID- 26839897 TI - The Actions of Lyophilized Apple Peel on the Electrical Activity and Organization of the Ventricular Syncytium of the Hearts of Diabetic Rats. AB - This study was designed to examine the effects of lyophilized red delicious apple peel (RDP) on the action potentials (APs) and the input resistance-threshold current relationship. The experiments were performed on isolated papillary heart muscles from healthy male rats, healthy male rats treated with RDP, diabetic male rats, and diabetic male rats treated with RDP. The preparation was superfused with oxygenated Tyrode's solution at 37 degrees C. The stimulation and the recording of the APs, the input resistance, and the threshold current were made using conventional electrophysiological methods. The RDP presented no significant effect in normal rats. Equivalent doses in diabetic rats reduced the APD and ARP. The relationship between input resistance and threshold current established an inverse correlation. The results indicate the following: (1) The functional structure of the cardiac ventricular syncytium in healthy rats is heterogeneous, in terms of input resistance and threshold current. Diabetes further accentuates the heterogeneity. (2) As a consequence, conduction block occurs and increases the possibility of reentrant arrhythmias. (3) These modifications in the ventricular syncytium, coupled with the increase in the ARP, are the adequate substrate so that, with diabetes, the heart becomes more arrhythmogenic. (4) RDP decreases the APD, the ARP, and most syncytium irregularity caused by diabetes. PMID- 26839899 TI - Inability of Some Commercial Assays to Measure Suppression of Glucagon Secretion. AB - Glucagon levels are increasingly being included as endpoints in clinical study design and more than 400 current diabetes-related clinical trials have glucagon as an outcome measure. The reliability of immune-based technologies used to measure endogenous glucagon concentrations is, therefore, important. We studied the ability of immunoassays based on four different technologies to detect changes in levels of glucagon under conditions where glucagon levels are strongly suppressed. To our surprise, the most advanced technological methods, employing electrochemiluminescence or homogeneous time resolved fluorescence (HTRF) detection, were not capable of detecting the suppression induced by a glucose clamp (6 mmol/L) with or without atropine in five healthy male participants, whereas a radioimmunoassay and a spectrophotometry-based ELISA were. In summary, measurement of glucagon is challenging even when state-of-the-art immune-based technologies are used. Clinical researchers using glucagon as outcome measures may need to reconsider the validity of their chosen glucagon assay. The current study demonstrates that the most advanced approach is not necessarily the best when measuring a low-abundant peptide such as glucagon in humans. PMID- 26839898 TI - Inhibition of MEK1 Signaling Pathway in the Liver Ameliorates Insulin Resistance. AB - Although mitogen-activated protein kinase kinase (MEK) is a key signaling molecule and a negative regulator of insulin action, it is still uncertain whether MEK can be a therapeutic target for amelioration of insulin resistance (IR) in type 2 diabetes (T2D) in vivo. To clarify whether MEK inhibition improves T2D, we examined the effect of continuous MEK inhibition with two structurally different MEK inhibitors, RO5126766 and RO4987655, in mouse models of T2D. RO5126766 and RO4987655 were administered via dietary admixture. Both compounds decreased blood glucose and improved glucose tolerance in doses sufficient to sustain inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation downstream of MEK in insulin-responsive tissues in db/db mice. A hyperinsulinemic-euglycemic clamp test showed increased glucose infusion rate (GIR) in db/db mice treated with these compounds, and about 60% of the increase was attributed to the inhibition of endogenous glucose production, suggesting that the liver is responsible for the improvement of IR. By means of adenovirus mediated Mek1 shRNA expression, we confirmed that blood glucose levels are reduced by suppression of MEK1 expression in the liver of db/db mice. Taken together, these results suggested that the MEK signaling pathway could be a novel therapeutic target for novel antidiabetic agents. PMID- 26839902 TI - The Spectrum of Medical Imaging in the 2015 International Year of Light. PMID- 26839903 TI - Optical tomography with discretized path integral. AB - We present a framework for optical tomography based on a path integral. Instead of directly solving the radiative transport equations, which have been widely used in optical tomography, we use a path integral that has been developed for rendering participating media based on the volume rendering equation in computer graphics. For a discretized two-dimensional layered grid, we develop an algorithm to estimate the extinction coefficients of each voxel with an interior point method. Numerical simulation results are shown to demonstrate that the proposed method works well. PMID- 26839904 TI - Spectral response model for a multibin photon-counting spectral computed tomography detector and its applications. AB - Variations among detector channels in computed tomography can lead to ring artifacts in the reconstructed images and biased estimates in projection-based material decomposition. Typically, the ring artifacts are corrected by compensation methods based on flat fielding, where transmission measurements are required for a number of material-thickness combinations. Phantoms used in these methods can be rather complex and require an extensive number of transmission measurements. Moreover, material decomposition needs knowledge of the individual response of each detector channel to account for the detector inhomogeneities. For this purpose, we have developed a spectral response model that binwise predicts the response of a multibin photon-counting detector individually for each detector channel. The spectral response model is performed in two steps. The first step employs a forward model to predict the expected numbers of photon counts, taking into account parameters such as the incident x-ray spectrum, absorption efficiency, and energy response of the detector. The second step utilizes a limited number of transmission measurements with a set of flat slabs of two absorber materials to fine-tune the model predictions, resulting in a good correspondence with the physical measurements. To verify the response model, we apply the model in two cases. First, the model is used in combination with a compensation method which requires an extensive number of transmission measurements to determine the necessary parameters. Our spectral response model successfully replaces these measurements by simulations, saving a significant amount of measurement time. Second, the spectral response model is used as the basis of the maximum likelihood approach for projection-based material decomposition. The reconstructed basis images show a good separation between the calcium-like material and the contrast agents, iodine and gadolinium. The contrast agent concentrations are reconstructed with more than 94% accuracy. PMID- 26839900 TI - MGL Receptor and Immunity: When the Ligand Can Make the Difference. AB - C-type lectin receptors (CLRs) on antigen-presenting cells (APCs) facilitate uptake of carbohydrate antigens for antigen presentation, modulating the immune response in infection, homeostasis, autoimmunity, allergy, and cancer. In this review, we focus on the role of the macrophage galactose type C-type lectin (MGL) in the immune response against self-antigens, pathogens, and tumor associated antigens (TAA). MGL is a CLR exclusively expressed by dendritic cells (DCs) and activated macrophages (MOs), able to recognize terminal GalNAc residues, including the sialylated and nonsialylated Tn antigens. We discuss the effects on DC function induced throughout the engagement of MGL, highlighting the importance of the antigen structure in the modulation of immune response. Indeed modifying Tn-density, the length, and steric structure of the Tn-antigens can result in generating immunogens that can efficiently bind to MGL, strongly activate DCs, mimic the effects of a danger signal, and achieve an efficient presentation in HLA classes I and II compartments. PMID- 26839901 TI - Serotype-dependent transduction efficiencies of recombinant adeno-associated viral vectors in monkey neocortex. AB - Viral vector-mediated expression of genes (e.g., coding for opsins and designer receptors) has grown increasingly popular. Cell-type specific expression is achieved by altering viral vector tropism through crosspackaging or by cell specific promoters driving gene expression. Detailed information about transduction properties of most recombinant adeno-associated viral vector (rAAV) serotypes in macaque cortex is gradually becoming available. Here, we compare transduction efficiencies and expression patterns of reporter genes in two macaque neocortical areas employing different rAAV serotypes and promoters. A short version of the calmodulin-kinase-II (CaMKIIalpha0.4) promoter resulted in reporter gene expression in cortical neurons for all tested rAAVs, albeit with different efficiencies for spread: rAAV2/5>>rAAV2/7>rAAV2/8>rAAV2/9>>rAAV2/1 and proportion of transduced cells: rAAV2/1>rAAV2/5>rAAV2/7=rAAV2/9>rAAV2/8. In contrast to rodent studies, the cytomegalovirus (CMV) promoter appeared least efficient in macaque cortex. The human synapsin-1 promoter preceded by the CMV enhancer (enhSyn1) produced homogeneous reporter gene expression across all layers, while two variants of the CaMKIIalpha promoter resulted in different laminar transduction patterns and cell specificities. Finally, differences in expression patterns were observed when the same viral vector was injected in two neocortical areas. Our results corroborate previous findings that reporter-gene expression patterns and efficiency of rAAV transduction depend on serotype, promoter, cortical layer, and area. PMID- 26839906 TI - Characterization of simulated incident scatter and the impact on quantification in dedicated breast single-photon emission computed tomography. AB - The objective was to characterize the changes seen from incident Monte Carlo based scatter distributions in dedicated three-dimensional (3-D) breast single photon emission computed tomography, with emphasis on the impact of scatter correction using the dual-energy window (DEW) method. Changes in scatter distributions with 3-D detector position were investigated for prone breast imaging with an ideal detector. Energy spectra within a high-energy scatter window measured from simulations were linearly fit, and the slope was used to characterize scatter distributions. The impact of detector position on the measured scatter fraction within various photopeak windows and the [Formula: see text] value (ratio of scatter within the photopeak and scatter energy windows) useful for scatter correction was determined. Results indicate that application of a single [Formula: see text] value with the DEW method in the presence of anisotropic object scatter distribution is not appropriate for trajectories including the heart and liver. The scatter spectra's slope demonstrates a strong correlation to measured [Formula: see text] values. Reconstructions of fixed-tilt 3-D acquisition trajectories with a single [Formula: see text] value show quantification errors up to 5% compared to primary-only reconstructions. However, a variable-tilt trajectory provides improved sampling and minimizes quantification errors, and thus allows for a single [Formula: see text] value to be used with the DEW method leading to more accurate quantification. PMID- 26839905 TI - Complementary contrast media for metal artifact reduction in dual-energy computed tomography. AB - Metal artifacts have been a problem associated with computed tomography (CT) since its introduction. Recent techniques to mitigate this problem have included utilization of high-energy (keV) virtual monochromatic spectral (VMS) images, produced via dual-energy CT (DECT). A problem with these high-keV images is that contrast enhancement provided by all commercially available contrast media is severely reduced. Contrast agents based on higher atomic number elements can maintain contrast at the higher energy levels where artifacts are reduced. This study evaluated three such candidate elements: bismuth, tantalum, and tungsten, as well as two conventional contrast elements: iodine and barium. A water-based phantom with vials containing these five elements in solution, as well as different artifact-producing metal structures, was scanned with a DECT scanner capable of rapid operating voltage switching. In the VMS datasets, substantial reductions in the contrast were observed for iodine and barium, which suffered from contrast reductions of 97% and 91%, respectively, at 140 versus 40 keV. In comparison under the same conditions, the candidate agents demonstrated contrast enhancement reductions of only 20%, 29%, and 32% for tungsten, tantalum, and bismuth, respectively. At 140 versus 40 keV, metal artifact severity was reduced by 57% to 85% depending on the phantom configuration. PMID- 26839907 TI - Hole filling with oriented sticks in ultrasound volume reconstruction. AB - Volumes reconstructed from tracked planar ultrasound images often contain regions where no information was recorded. Existing interpolation methods introduce image artifacts and tend to be slow in filling large missing regions. Our goal was to develop a computationally efficient method that fills missing regions while adequately preserving image features. We use directional sticks to interpolate between pairs of known opposing voxels in nearby images. We tested our method on 30 volumetric ultrasound scans acquired from human subjects, and compared its performance to that of other published hole-filling methods. Reconstruction accuracy, fidelity, and time were improved compared with other methods. PMID- 26839908 TI - Special Section Guest Editorial:Radiomics and Imaging Genomics: Quantitative Imaging for Precision Medicine. PMID- 26839909 TI - Imaging-genomic pipeline for identifying gene mutations using three-dimensional intra-tumor heterogeneity features. AB - This paper presents an imaging-genomic pipeline to derive three-dimensional intra tumor heterogeneity features from contrast-enhanced CT images and correlates them with gene mutation status. The pipeline has been demonstrated using CT scans of patients with clear cell renal cell carcinoma (ccRCC) from The Cancer Genome Atlas. About 15% of ccRCC cases reported have BRCA1-associated protein 1 (BAP1) gene alterations that are associated with high tumor grade and poor prognosis. We hypothesized that BAP1 mutation status can be detected using computationally derived image features. The molecular data pertaining to gene mutation status were obtained from the cBioPortal. Correlation of the image features with gene mutation status was assessed using the Mann-Whitney-Wilcoxon rank-sum test. We also used the random forests classifier in the Waikato Environment for Knowledge Analysis software to assess the predictive ability of the computationally derived image features to discriminate cases with BAP1 mutations for ccRCC. Receiver operating characteristics were obtained using a leave-one-out-cross-validation procedure. Our results show that our model can predict BAP1 mutation status with a high degree of sensitivity and specificity. This framework demonstrates a methodology for noninvasive disease biomarker detection from contrast-enhanced CT images. PMID- 26839910 TI - Experimental validation of L-shell x-ray fluorescence computed tomography imaging: phantom study. AB - Thanks to the current advances in nanoscience, molecular biochemistry, and x-ray detector technology, x-ray fluorescence computed tomography (XFCT) has been considered for molecular imaging of probes containing high atomic number elements, such as gold nanoparticles. The commonly used XFCT imaging performed with K-shell x rays appears to have insufficient imaging sensitivity to detect the low gold concentrations observed in small animal studies. Low energy fluorescence L-shell x rays have exhibited higher signal-to-background ratio and appeared as a promising XFCT mode with greatly enhanced sensitivity. The aim of this work was to experimentally demonstrate the feasibility of L-shell XFCT imaging and to assess its achievable sensitivity. We built an experimental L shell XFCT imaging system consisting of a miniature x-ray tube and two spectrometers, a silicon drift detector (SDD), and a CdTe detector placed at [Formula: see text] with respect to the excitation beam. We imaged a 28-mm diameter water phantom with 4-mm-diameter Eppendorf tubes containing gold solutions with concentrations of 0.06 to 0.1% Au. While all Au vials were detectable in the SDD L-shell XFCT image, none of the vials were visible in the CdTe L-shell XFCT image. The detectability limit of the presented L-shell XFCT SDD imaging setup was 0.007% Au, a concentration observed in small animal studies. PMID- 26839911 TI - Light source design for spectral tuning in biomedical imaging. AB - We propose an architecture with a remote phosphor-based modular and compact light emitting diode (LED) light source in a noncontact dermoscope prototype for skin cancer screening. The spectrum and color temperature of the output light can easily and significantly be changed depending on spectral absorption characteristics of the tissues being imaged. The new system has several advantages compared to state-of-the-art phosphor converted ultrabright white LEDs, used in a wide range of medical imaging devices, which have a fixed spectrum and color temperature at a given operating point. In particular, the system can more easily be adapted to the requirements originating from different tissues in the human body, which have wavelength-dependent absorption and reflectivity. This leads to improved contrast for different kinds of imaged tissue components. The concept of such a lighting architecture can be vastly utilized in many other medical imaging devices including endoscopic systems. PMID- 26839913 TI - Factors affecting the normality of channel outputs of channelized model observers: an investigation using realistic myocardial perfusion SPECT images. AB - The channelized Hotelling observer (CHO) uses the first- and second-order statistics of channel outputs under both hypotheses to compute test statistics used in binary classification tasks. If these input data deviate from a multivariate normal (MVN) distribution, the classification performance will be suboptimal compared to an ideal observer operating on the same channel outputs. We conducted a comprehensive investigation to rigorously study the validity of the MVN assumption under various kinds of background and signal variability in a realistic population of phantoms. The study was performed in the context of myocardial perfusion SPECT imaging; anatomical, uptake (intensity), and signal variability were simulated. Quantitative measures and graphical approaches applied to the outputs of each channel were used to investigate the amount and type of deviation from normality. For some types of background and signal variations, the channel outputs, under both hypotheses, were non-normal (i.e., skewed or multimodal). This indicates that, for realistic medical images in cases where there is signal or background variability, the normality of the channel outputs should be evaluated before applying a CHO. Finally, the different degrees of departure from normality of the various channels are explained in terms of violations of the central limit theorem. PMID- 26839914 TI - Watermarking of ultrasound medical images in teleradiology using compressed watermark. AB - The open accessibility of Internet-based medical images in teleradialogy face security threats due to the nonsecured communication media. This paper discusses the spatial domain watermarking of ultrasound medical images for content authentication, tamper detection, and lossless recovery. For this purpose, the image is divided into two main parts, the region of interest (ROI) and region of noninterest (RONI). The defined ROI and its hash value are combined as watermark, lossless compressed, and embedded into the RONI part of images at pixel's least significant bits (LSBs). The watermark lossless compression and embedding at pixel's LSBs preserve image diagnostic and perceptual qualities. Different lossless compression techniques including Lempel-Ziv-Welch (LZW) were tested for watermark compression. The performances of these techniques were compared based on more bit reduction and compression ratio. LZW was found better than others and used in tamper detection and recovery watermarking of medical images (TDARWMI) scheme development to be used for ROI authentication, tamper detection, localization, and lossless recovery. TDARWMI performance was compared and found to be better than other watermarking schemes. PMID- 26839916 TI - Studies on Labour Safety in Construction Sites. AB - Construction industry has accomplished extensive growth worldwide particularly in past few decades. For a construction project to be successful, safety of the structures as well as that of the personnel is of utmost importance. The safety issues are to be considered right from the design stage till the completion and handing over of the structure. Construction industry employs skilled and unskilled labourers subject to construction site accidents and health risks. A proper coordination between contractors, clients, and workforce is needed for safe work conditions which are very much lacking in Indian construction companies. Though labour safety laws are available, the numerous accidents taking place at construction sites are continuing. Management commitment towards health and safety of the workers is also lagging. A detailed literature study was carried out to understand the causes of accidents, preventive measures, and development of safe work environment. This paper presents the results of a questionnaire survey, which was distributed among various categories of construction workers in Kerala region. The paper examines and discusses in detail the total working hours, work shifts, nativity of the workers, number of accidents, and type of injuries taking place in small and large construction sites. PMID- 26839915 TI - Conduction abnormalities and ventricular arrhythmogenesis: The roles of sodium channels and gap junctions. AB - Ventricular arrhythmias arise from disruptions in the normal orderly sequence of electrical activation and recovery of the heart. They can be categorized into disorders affecting predominantly cellular depolarization or repolarization, or those involving action potential (AP) conduction. This article briefly discusses the factors causing conduction abnormalities in the form of unidirectional conduction block and reduced conduction velocity (CV). It then examines the roles that sodium channels and gap junctions play in AP conduction. Finally, it synthesizes experimental results to illustrate molecular mechanisms of how abnormalities in these proteins contribute to such conduction abnormalities and hence ventricular arrhythmogenesis, in acquired pathologies such as acute ischaemia and heart failure, as well as inherited arrhythmic syndromes. PMID- 26839917 TI - Climbing Fiber Regulation of Spontaneous Purkinje Cell Activity and Cerebellum Dependent Blink Responses(1,2,3). AB - It has been known for a long time that GABAergic Purkinje cells in the cerebellar cortex, as well as their target neurons in the cerebellar nuclei, are spontaneously active. The cerebellar output will, therefore, depend on how input is integrated into this spontaneous activity. It has been shown that input from climbing fibers originating in the inferior olive controls the spontaneous activity in Purkinje cells. While blocking climbing fiber input to the Purkinje cells causes a dramatic increase in the firing rate, increased climbing fiber activity results in reduced Purkinje cell activity. However, the exact calibration of this regulation has not been examined systematically. Here we examine the relation between climbing fiber stimulation frequency and Purkinje cell activity in unanesthetized decerebrated ferrets. The results revealed a gradual suppression of Purkinje cell activity, starting at climbing fiber stimulation frequencies as low as 0.5 Hz. At 4 Hz, Purkinje cells were completely silenced. This effect lasted an average of 2 min after the stimulation rate was reduced to a lower level. We also examined the effect of sustained climbing fiber stimulation on overt behavior. Specifically, we analyzed conditioned blink responses, which are known to be dependent on the cerebellum, while stimulating the climbing fibers at different frequencies. In accordance with the neurophysiological data, the conditioned blink responses were suppressed at stimulation frequencies of >=4 Hz. PMID- 26839919 TI - The University College London/Medical Research Council/National Institute of Health Research-Health Technology Assessment PROMIS Trial: An Update. PMID- 26839920 TI - Exonuclease I-aided homogeneous electrochemical strategy for organophosphorus pesticide detection based on enzyme inhibition integrated with a DNA conformational switch. AB - A novel enzyme inhibition-based homogeneous electrochemical biosensing strategy was designed for an organophosphorus pesticide assay based on exploiting the resistance of a mercury ion-mediated helper probe (HP) toward nuclease-catalyzed digestion and the remarkable diffusivity difference between HPs and the mononucleotides toward a negatively charged indium tin oxide (ITO) electrode. In particular, the mercury ion-mediated T-Hg(2+)-T base pairs facilitate the HP labeled with methylene blue (MB) to fold into a hairpin structure, preventing its digestion by exonuclease I, and thus resulting in a low electrochemical response because of the large electrostatic repulsion between the negatively charged ITO electrode and the HPs. The competitive binding by a thiol group (-SH), produced in the hydrolysis reaction of acetylthiocholine (ACh) chloride with acetylcholinesterase (AChE), removes mercury ions from the base pairs, causing a nuclease-catalyzed digestion, and the subsequent electrochemical response increase due to the weak electrostatic repulsion between the product mononucleotides and the ITO electrode. Mercury ion-mediated HPs were first designed for pesticide detection and diazinon was chosen as the model target. Under the optimal experimental conditions, the approach exhibited high sensitivity for diazinon detection with a detection limit of 0.25 MUg L(-1). The satisfactory results in the determination of diazinon in real samples demonstrate that the method possesses great potential for detecting organophosphorus pesticides. This new approach is expected to promote the exploitation of mercury mediated base pair-based homogenous electrochemical biosensors in biochemical studies and in the food safety field. PMID- 26839921 TI - Multi-dimensional on-particle detection technology for multi-category disease classification. AB - A serum peptide profile contains important bio-information, which may help disease classification. The motivation of this study is to take advantage of porous silicon microparticles with multiple surface chemistries to reduce the loss of peptide information and simplify the sample pretreatment. We developed a multi-dimensional on-particle MALDI-TOF technology to acquire high fidelity and cross-reactive molecular fingerprints for mining disease information. The peptide fingerprint of serum samples from colorectal cancer patients, liver cancer patients and healthy volunteers were measured with this technology. The featured mass spectral peaks can successfully discriminate and predict the multi-category disease. Data visualization for future clinical application was also demonstrated. PMID- 26839918 TI - ERalpha Signaling Is Required for TrkB-Mediated Hippocampal Neuroprotection in Female Neonatal Mice after Hypoxic Ischemic Encephalopathy(1,2,3). AB - Male neonate brains are more susceptible to the effects of perinatal asphyxia resulting in hypoxia and ischemia (HI)-related brain injury. The relative resistance of female neonatal brains to adverse consequences of HI suggests that there are sex-specific mechanisms that afford females greater neuroprotection and/or facilitates recovery post-HI. We hypothesized that HI preferentially induces estrogen receptor alpha (ERalpha) expression in female neonatal hippocampi and that ERalpha is coupled to Src family kinase (SFK) activation that in turn augments phosphorylation of the TrkB and thereby results in decreased apoptosis. After inducing the Vannucci's HI model on P9 (C57BL/6J) mice, female and male ERalpha wild-type (ERalpha(+/+)) or ERalpha null mutant (ERalpha(-/-)) mice received vehicle control or the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF). Hippocampi were collected for analysis of mRNA of ERalpha and BDNF, protein levels of ERalpha, p-TrkB, p-src, and cleaved caspase 3 (c-caspase-3) post-HI. Our results demonstrate that: (1) HI differentially induces ERalpha expression in the hippocampus of the female versus male neonate, (2) src and TrkB phosphorylation post-HI is greater in females than in males after 7,8-DHF therapy, (3) src and TrkB phosphorylation post-HI depend on the presence of ERalpha, and (4) TrkB agonist therapy decreases the c-caspase-3 only in ERalpha(+/+) female mice hippocampus. Together, these observations provide evidence that female-specific induction of ERalpha expression confers neuroprotection with TrkB agonist therapy via SFK activation and account for improved functional outcomes in female neonates post-HI. PMID- 26839922 TI - Oxidation-triggered aggregation of gold nanoparticles for naked-eye detection of hydrogen peroxide. AB - Naked-eye detection of H2O2 was realized based on the color change of gold nanoparticles upon aggregation. The removal of polyethylene glycol chains from the nanoparticle surface under H2O2 treatment let to the exposure of inner hydrophobic ligands, causing the nanoparticle aggregation in aqueous medium. This detection system shows a wide dynamic range in the MUM scale and a distinguishable limit of 10 MUM. PMID- 26839923 TI - The preparation of hierarchical SAPO-34 crystals via post-synthesis fluoride etching. AB - SAPO-34 crystals are etched in fluoride medium. The interface between crystalline domains is dissolved and yields a hierarchical material with a system of straight intersecting mesopores that improve the access to micropore space. PMID- 26839924 TI - Got LiZnP? Solution phase synthesis of filled tetrahedral semiconductors in the nanoregime. AB - We report the synthesis and characterization of nanocrystalline LiZnP. The reaction proceeds through a zinc metal intermediate followed by rapid incorporation of lithium and phosphorus. We demonstrate flexibility in the selection of Li, Zn, and P precursors, as well as extension of this method to other half-Heusler phases. PMID- 26839926 TI - Voltage-responsive single-chain polymer nanoparticles via host-guest interaction. AB - Poly(N-(2-hydroxyethyl)acrylamide) with pendant beta-cyclodextrin was synthesized and intramolecularly crosslinked with bridged bis(ferrocene). This supramolecular nanoparticle can be changed reversibly between a coil and a nanoparticle upon external voltage stimuli. PMID- 26839925 TI - Reprogrammable multiplexed detection of circulating oncomiRs using hybridization chain reaction. AB - In this study, we have coupled the DNA polymerization capability of hybridization chain reaction (HCR) with the plasmonic properties of gold nanoparticles to develop a reprogrammable and multiplexed detection of three circulating oncomiRs (miR-10b, miR-21 and miR-141) dysregulated in various disease states of breast cancer. We have demonstrated that by simply changing the initiator (label-free short single stranded DNA) content of the HCR, while keeping everything else unchanged, the same nanoparticle assembly can be reprogrammed for the detection of the target oncomiRs individually or simultaneously in all possible combinations. We have shown that as little as 20 femtomoles of each oncomiR can be detected visually without using any analytical instrument. Furthermore, we demonstrated that the target oncomiR can be detected in an RNA pool isolated from a liquid biopsy mimic of breast cancer. PMID- 26839927 TI - Cylindrical dye-sensitized solar cells with high efficiency and stability over time and incident angle. AB - We present here the realization of cylindrical dye-sensitized solar cells composed of Ti wire supported TiO2 nanotube anodes and transparent metal selenide counter electrodes. The optimized device yields a high efficiency of 6.63%, good stability over time, and identical efficiency output at arbitrary incident angles. PMID- 26839928 TI - On the nature of the stabilisation of the E...pi pnicogen bond in the SbCl3...toluene complex. AB - The off-symmetrical structure of the toluene...SbCl3 complex is a consequence of the off-centre location of sigma-holes at the Sb atom. DFT-SAPT calculations have been used to determine the total interaction energies and their components. The characteristic features of the pnicogen bonding are due to the concert action of electrostatic and dispersion interactions. PMID- 26839929 TI - Bronsted acid-catalysed conjugate addition of photochemically generated alpha amino radicals to alkenylpyridines. AB - The conjugate addition of alpha-amino radicals to alkenylpyridines has been accomplished by the synergistic merger of Bronsted acid and visible light photoredox catalysis. Key to reaction development was the protonation of the alkenylpyridines that transiently generated a highly reactive, electrophilic pseudo-iminium ion intermediate. Initial investigations using chiral phosphoric acids provide clues on the feasibility of an enantioselective catalytic variant. PMID- 26839930 TI - Guest Editorial - Special Issue on Synthetic Biology. PMID- 26839932 TI - [In Process Citation]. PMID- 26839931 TI - [Guideline for off-label use of psychotropic drugs in children and adolescents]. AB - Off-label use is the practice of prescribing pharmaceuticals for an unapproved indication or in an unapproved age group, unapproved dose or unapproved form of administration. Many psychotropic drugs are not put through the rigorous formal process required to officially approve the drug for use in children and adolescents. If no approved drugs are available for a specific indication, child psychiatrists have to decide, whether to utilize the corresponding product authorized for adults, or not to treat with drugs. In many cases non-treatment would not be in line with the legal and moral duty to care and would be assessed as a breach of statutory duty of care in a liability proceeding. Off-label use of drugs requests extended obligation to inform because of enlarged needs of information of patients and parents. The present guideline makes recommendations for child and adolescent psychiatrists of the principle of the obligation to care as well as legal and moral considerations. PMID- 26839933 TI - Reply to Pierce at al. PMID- 26839934 TI - Breo Ellipta: An Inhaled Fluticasone/ Vilanterol Combination for COPD. PMID- 26839935 TI - Author Response. PMID- 26839937 TI - Obituary of Dr. Randall R. Sakai. PMID- 26839936 TI - Author Response. PMID- 26839938 TI - Deep sea in deep trouble? AB - Ahead of the imminent start of the industrial exploitation of deep sea resources, an EU report finds that scientific knowledge and understanding of this environment and its ecosystems still fall short of what would be needed for a sustainable use. PMID- 26839939 TI - Tatsuo Fukagawa. PMID- 26839941 TI - Equitable Imagery in the Preclinical Medical School Curriculum: Findings From One Medical School. AB - PURPOSE: The unequal representation of women and people of color compared with men and whites in medical school textbooks has been well documented, as have health care inequities, and biases-both overt and implicit-by health care providers and in access to care. The authors investigated whether this bias exists in PowerPoint slides used in didactic material for preclinical students at one medical school. METHOD: The authors analyzed 747 "decks" of slides from 33 preclinical courses in the medical school curriculum at the University of Washington School of Medicine in the years spanning 2009 to 2011. The authors coded the human images into various sex- and race-specific classifications and evaluated the distribution of images into these categories. RESULTS: Of the 4,033 images that could be coded by sex, 39.6% (1,595) were female and 60.5% (2,438) were male. Of the 5,230 images that could be coded by race/ethnicity, 78.4% (4,100) were white and 21.6% (1,130) were persons of color. Thus, images of whites and males predominated. CONCLUSIONS: The proportion of images used in didactic courses at one school of medicine is not representative of the U.S. population in terms of race or sex. The authors discuss the potential sources and impact of this bias, make a case for sex and race diversity in didactic imagery, and propose possible avenues for further research and curricular reform in an era when the population is becoming increasingly racially and ethnically diverse. PMID- 26839942 TI - Educational Value Units: A Mission-Based Approach to Assigning and Monitoring Faculty Teaching Activities in an Academic Medical Department. AB - PROBLEM: Increasing emphasis on revenue generation could jeopardize the fundamental notion of what it means to be faculty. Despite being a core mission, education is often marginalized in academic medical departments, and expectations of faculty effort in this area are often vague. A potential solution is mission based budgeting (MBB), which refers to the allocation of resources based on core mission-related priorities. APPROACH: From December 2012 to March 2013, the authors developed an educational value unit (EVU) system (using an MBB approach) to assign and monitor teaching activities related to the core departmental educational mission at the Department of Emergency Medicine, Johns Hopkins Medicine. EVUs were based on learner contact time, with one EVU equal to roughly one hour of in-person time with medical students or residents. Core education faculty vetted the proposed system; educational leaders determined the total EVUs needed and assessed the impact of their equitable distribution among faculty; and faculty members selected preferences and were assigned EVU obligations. OUTCOMES: For academic year 2013-2014, 5,896 EVUs were distributed among 54 faculty. At the end of the year, complete EVU data were available for 47 faculty. Of these, only 6 failed to complete their assigned EVU obligations. All core teaching activities were covered, and educational efforts were distributed more equitably across faculty. NEXT STEPS: The system is being refined, with an emphasis on incorporating learner outcome metrics, refining the teaching grid, incorporating failure to meet EVU obligations into yearly faculty evaluations, and disseminating the system to other departments and institutions. PMID- 26839940 TI - Protective effect of yellow tea extract on N-nitrosodiethylamine-induced liver carcinogenesis. AB - Context Yellow tea containing the same catechins as other types of tea but in different proportions has been suggested to possess potent anticancer activities. Objective This study investigates the chemopreventive effect of yellow tea aqueous extract against N-nitrosodiethylamine (NDEA)-induced liver carcinogenesis in rats by employing histological and biochemical methods. Materials and methods Wistar rats were divided randomly into four groups: control (I), yellow tea (II), NDEA (III), and yellow tea + NDEA (IV). Groups II and IV were exposed via a diet to yellow tea extract in a concentration of 10 g/kg feed; groups III and IV received 0.01% NDEA in drinking water. The experiment lasted for 13 weeks. Results Daily intake of yellow tea in an average dose of 800 mg/kg b.w. alleviated the carcinogenic effect of NDEA as evidenced by reversed histopathological changes towards normal hepatocellular architecture and decreased lipid peroxidation, protein carbonyl formation, and DNA degradation by 64%, 37% and 15%, respectively, as compared with values obtained in NDEA alone treated rats. Treatment with yellow tea extract caused protection of superoxide dismutase (SOD) and catalase (CAT); their activity was recovered by 47% and 12%, respectively, as compared with the NDEA-treated rats. Moreover, the extract normalized the NDEA-induced activity of paraoxonase 1 (PON1) and glutathione peroxidase (GPx), while a further increase in the level of reduced glutathione (GSH) was noticed. Conclusions On the basis of these findings, it can be concluded that treatment with yellow tea partially protected the livers of rats from NDEA-induced hepatocarcinogenesis and that its antioxidant activity contributed to this effect. PMID- 26839943 TI - Getting (Along) With the Guidelines: Reconciling Patient Autonomy and Quality Improvement Through Shared Decision Making. AB - In past decades, stark differences in practice pattern, cost, and outcomes of care across regions with similar health demographics have prompted calls for reform. As health systems answer the growing call for accountability in the form of quality indices, while responding to increased scrutiny on practice variation in the form of pay for performance (P4P), a rift is widening between the system and individual patients. Currently, three areas are inadequately considered by P4P structures based largely on physician adherence to guidelines: diversity of patient values and preferences; time and financial burden of therapy in the context of multimorbidity; and narrow focus on quantitative measures that distract clinicians from providing optimal care. As health care reform efforts place greater emphasis on value-for-money of care delivered, they provide an opportunity to consider the other "value"-the values of each patient and care delivery that aligns with them.The inherent balance of risks and benefits in every treatment, especially those involving chronic conditions, calls for engagement of patients in decision-making processes, recognizing the diversity of preferences at the individual level. Shared decision making (SDM) is an attractive option and should be an essential component of quality health care rather than its adjunct. Four interwoven steps toward the meaningful implementation of SDM in clinical practice-embedding SDM as a health care quality measure, "real-world" evaluation of SDM effectiveness, pursuit of an SDM favorable health system, and patient-centered medical education-are proposed to bring focus back to the beneficiary of health care accountability, the patient. PMID- 26839944 TI - The Ambulatory Diagnostic and Treatment Center: A Unique Model for Educating Medical Trainees and Providing Expedited Care. AB - In this article, the authors reexamine the Ambulatory Diagnostic and Treatment Center (ADTC) model, which uniquely combines the education of trainees with the care of referred patients at one Veterans Affairs medical center. As an ambulatory clinic with an inpatient mind-set, the ADTC uses a series of closely spaced outpatient appointments that are longer than typical ambulatory visits, offering a VIP-level of evaluation with the patient-centered goal of expedited diagnosis and treatment. Faculty triage patients by weighing factors such as urgency, educational value, complexity, and instability of diseases in conjunction with the resources, availability, and appropriateness of other services within the medical center.The ADTC's unique focus on the education of trainees in comparison with other clinical rotations is evident in the ratio of learning to patient care. This intensive training environment expects postgraduate year 2 and 3 internal medicine residents and fourth-year medical students to read, reflect, and review literature daily. This mix of education and care delivery is ripe for reexploration in light of recent calls for curriculum reform amidst headlines exposing delays in veterans' access to care.A low-volume, high-intensity clinic like the ADTC can augment the clinical services provided by a busy primary care and subspecialty workforce without losing its emphasis on education. Other academic health centers can learn from this model and adapt its structure in settings where accountable care organizations and education meet. PMID- 26839945 TI - Consequences Validity Evidence: Evaluating the Impact of Educational Assessments. AB - Because tests that do not alter management (i.e., influence decisions and actions) should not be performed, data on the consequences of assessment constitute a critical source of validity evidence. Consequences validity evidence is challenging for many educators to understand, perhaps because it has no counterpart in the older framework of content, criterion, and construct validity. The authors' purpose is to explain consequences validity evidence and propose a framework for organizing its collection and interpretation.Both clinical and educational assessments can be viewed as interventions. The act of administering or taking a test, the interpretation of scores, and the ensuing decisions and actions influence those being assessed (e.g., patients or students) and other people and systems (e.g., physicians, teachers, hospitals, schools). Consequences validity evidence examines such impacts of assessments. Despite its importance, consequences evidence is reported infrequently in health professions education (range 5%-20% of studies in recent systematic reviews) and is typically limited in scope and rigor.Consequences validity evidence can derive from evaluations of the impact on examinees, educators, schools, or the end target of practice (e.g., patients or health care systems); and the downstream impact of classifications (e.g., different score cut points and labels). Impact can result from the uses of scores or from the assessment activity itself, and can be intended or unintended and beneficial or harmful. Both quantitative and qualitative research methods are useful. The type, quantity, and rigor of consequences evidence required will vary depending on the assessment and the claims for its use. PMID- 26839946 TI - At a Crossroads: The Future of Primary Care Education and Practice. AB - Academic medical centers are under increasing scrutiny to provide both timely, high-quality primary care (PC) and health professional education. The complexity of these issues will require innovative multipronged solutions aimed at academic ambulatory PC training programs. In this issue, Serrao and Orlander describe one model that may address some of these issues: the Ambulatory Diagnostic and Treatment Center (ADTC) in the Veterans Affairs Boston Healthcare System. The ADTC model offers primary care providers (PCPs) the opportunity to refer an especially complex patient to a team of PC faculty and trainees who are not familiar with the patient but who have more time and resources to dedicate to her or his care. The ADTC is one model that may mitigate some of the tension between patient care and education in PC settings. Another model is the West Haven Veterans Affairs Center of Excellence in Primary Care Education program, in which interprofessional teams of faculty and trainees are assigned to care for a panel of patients. Creative solutions to overcoming the barriers to providing timely, high-quality care as well as a commitment to providing sufficient time and quality in PC education are essential. These solutions must include models of education and care that (1) preserve PCP-patient continuity, (2) allow more time for complex patient visits, and (3) integrate interprofessional teams to support PCPs. These models will afford patients, providers, and trainees sufficient time for patient care, continuous relationships, learning, and reflection, resulting in improved satisfaction and more meaningful work. PMID- 26839947 TI - Lipopolysaccharide Neutralization by Cationic-Amphiphilic Polymers through Pseudoaggregate Formation. AB - Synthetic polymers incorporating the cationic charge and hydrophobicity to mimic the function of antimicrobial peptides (AMPs) have been developed. These cationic amphiphilic polymers bind to bacterial membranes that generally contain negatively charged phospholipids and cause membrane disintegration resulting in cell death; however, cationic-amphiphilic antibacterial polymers with endotoxin neutralization properties, to the best of our knowledge, have not been reported. Bacterial endotoxins such as lipopolysaccharide (LPS) cause sepsis that is responsible for a great amount of mortality worldwide. These cationic-amphiphilic polymers can also bind to negatively charged and hydrophobic LPS and cause detoxification. Hence, we envisaged that cationic-amphiphilic polymers can have both antibacterial as well as LPS binding properties. Here we report synthetic amphiphilic polymers with both antibacterial as well as endotoxin neutralizing properties. Levels of proinflammatory cytokines in human monocytes caused by LPS stimulation were inhibited by >80% when coincubated with these polymers. These reductions were found to be dependent on concentration and, more importantly, on the side-chain chemical structure due to variations in the hydrophobicity profiles of these polymers. These cationic-amphiphilic polymers bind and cause LPS neutralization and detoxification. Investigations of polymer interaction with LPS using fluorescence spectroscopy and dynamic light scattering (DLS) showed that these polymers bind but neither dissociate nor promote LPS aggregation. We show that polymer binding to LPS leads to sort of a pseudoaggregate formation resulting in LPS neutralization/detoxification. These findings provide an unusual mechanism of LPS neutralization using novel synthetic cationic-amphiphilic polymers. PMID- 26839949 TI - Developing a Social, Cultural and Economic Report Card for a Regional Industrial Harbour. AB - Report cards are increasingly used to provide ongoing snap-shots of progress towards specific ecosystem health goals, particularly in coastal regions where planners need to balance competing demands for coastal resources from a range of industries. While most previous report cards focus on the biophysical components of the system, there is a growing interest in including the social and economic implications of ecosystem management to provide a greater social-ecological system understanding. Such a report card was requested on the Gladstone Harbour area in central Queensland, Australia. Gladstone Harbour adjoins the southern Great Barrier Reef, and is also a major industrial and shipping port. Balancing social, economic and environmental interests is therefore of great concern to the regional managers. While environmental benchmarking procedures are well established within Australia (and elsewhere), a method for assessing social and economic performance of coastal management is generally lacking. The key aim of this study was to develop and pilot a system for the development of a report card relating to appropriate cultural, social and economic objectives. The approach developed uses a range of multicriteria decision analysis methods to assess and combine different qualitative and quantitative measures, including the use of Bayesian Belief Networks to combine the different measures and provide an overall quantitative score for each of the key management objectives. The approach developed is readily transferable for purposes of similar assessments in other regions. PMID- 26839948 TI - Liver specific expression of Cu/ZnSOD extends the lifespan of Sod1 null mice. AB - Genetic ablation of CuZn-superoxide dismutase (Sod1) in mice (Sod1(-/-) mice) leads to shortened lifespan with a dramatic increase in hepatocellular carcinoma and accelerated aging phenotypes, including early onset sarcopenia. To study the tissue specific effects of oxidative stress in the Sod1(-/-) mice, we generated mice that only express the human SOD1 gene specifically in the liver of Sod1(-/-) mice (Sod1(-/-)/hSOD1(alb) mice). Expression of hSOD1 in the liver of Sod1(-/-) mice improved liver function, reduced oxidative damage in liver, and partially restored the expression of several genes involved in tumorigenesis, which are abnormally expressed in the livers of the Sod1(-/-) mice. However, liver specific expression of hSOD1 did not prevent the loss of body weight and muscle mass and alterations in the structure of neuromuscular junctions. The expression of hSOD1 in the liver of Sod1(-/-) mice significantly improved the lifespan of Sod1(-/-) mice; however, the lifespan of the Sod1(-/-)/hSOD1(alb) mice was still significantly shorter than wild type mice. PMID- 26839951 TI - Correction: Sustained Endothelial Expression of HoxA5 In Vivo Impairs Pathological Angiogenesis And Tumor Progression. PMID- 26839950 TI - Complete mitochondrial genome of the Verticillium-wilt causing plant pathogen Verticillium nonalfalfae. AB - Verticillium nonalfalfae is a fungal plant pathogen that causes wilt disease by colonizing the vascular tissues of host plants. The disease induced by hop isolates of V. nonalfalfae manifests in two different forms, ranging from mild symptoms to complete plant dieback, caused by mild and lethal pathotypes, respectively. Pathogenicity variations between the causal strains have been attributed to differences in genomic sequences and perhaps also to differences in their mitochondrial genomes. We used data from our recent Illumina NGS-based project of genome sequencing V. nonalfalfae to study the mitochondrial genomes of its different strains. The aim of the research was to prepare a V. nonalfalfae reference mitochondrial genome and to determine its phylogenetic placement in the fungal kingdom. The resulting 26,139 bp circular DNA molecule contains a full complement of the 14 "standard" fungal mitochondrial protein-coding genes of the electron transport chain and ATP synthase subunits, together with a small rRNA subunit, a large rRNA subunit, which contains ribosomal protein S3 encoded within a type IA-intron and 26 tRNAs. Phylogenetic analysis of this mitochondrial genome placed it in the Verticillium spp. lineage in the Glomerellales group, which is also supported by previous phylogenetic studies based on nuclear markers. The clustering with the closely related Verticillium dahliae mitochondrial genome showed a very conserved synteny and a high sequence similarity. Two distinguishing mitochondrial genome features were also found-a potential long non coding RNA (orf414) contained only in the Verticillium spp. of the fungal kingdom, and a specific fragment length polymorphism observed only in V. dahliae and V. nubilum of all the Verticillium spp., thus showing potential as a species specific biomarker. PMID- 26839952 TI - Assessment of the psychosocial impacts of cochlear implants on adult recipients and their partners. AB - OBJECTIVES: In the present study we sought to evaluate the psychosocial and quality of life (QOL) impacts of cochlear implant (CI) treatment on both CI recipients and their partners in a Canadian population. METHODS: A qualitative cross-sectional contemporary cohort evaluation was conducted by distributing specifically designed questionnaires to both CI recipients and their partners at their follow-up appointments over a month at Sunnybrook Health Sciences Centre. RESULTS: It was found that both CI recipients and their partners demonstrated substantial benefit and improvement in multiple psychosocial domains. DISCUSSION: Musical listening was found to show variable improvements between recipients. Further analysis found a simple correlation where the group of recipients who all had a hearing disability for a longer duration had demonstrated a higher proportion of improvement in musical listening. CI recipients endorsed having improved QOL which was in agreement with proxy observation by partners. CONCLUSION: Overall, CI use has been shown to have significant benefit to psychosocial well-being of CI recipients. This benefit is also conferred to their caregivers/partners; which in our society concerned about caregiver burden is quite important to recognize. PMID- 26839953 TI - Occlusal Caries Management: Preferences among Dentists in Norway. AB - The aim was to measure variations in the threshold for operative treatment of occlusal caries in permanent teeth and the use of dental materials, compared with results from a similar study conducted in Norway in 1995. In 2009, a precoded questionnaire was sent electronically to 3,654 dentists with E-mail addresses in the member register of the Norwegian Dental Association. The questions were related to caries, treatment strategies and choice of dental materials. Replies were obtained from 61.3% respondents after two reminders. Restorative treatment of occlusal lesions confined to enamel was proposed by 12% of the dentists, compared with 18% in 1995 (p < 0.01). Older dentists more often than younger dentists would operatively treat enamel lesions (p < 0.01). Most dentists preferred to drill only the carious part of the fissure rather than the whole fissure both in 2009 (78.8%) and 1995 (68.3%; p < 0.01). In 2009, 91.9% preferred composite as the restorative material of choice, compared to only 39.1% in 1995. Logistic regression analyses identified higher age of the dentist as the only variable significantly associated with higher risk of restoring occlusal enamel lesions operatively. The authors conclude that especially young dentists appear to be more reluctant to remove tooth substance in 2009 compared with 1995. Composite is the dominating material of choice in 2009 and seems to have substituted the use of most other filling materials in occlusal restorations in permanent teeth. PMID- 26839954 TI - Synthesis and comparative evaluation of novel (64)Cu-labeled high affinity cell specific peptides for positron emission tomography imaging of tumor vasculature. AB - Tumor angiogenesis, the formation of new tumor blood supply, has been recognized as a hallmark of cancer and represents an important target for clinical management of various angiogenesis-dependent solid tumors. Previously, by screening a bacteriophage peptide library we have discovered the FHT-peptide sequence that binds specifically to bone marrow-derived tumor vasculature with high affinity. Here in an effort to determine the potential of the FHT-peptide for in vivo positron emission tomography (PET) imaging of aggressive tumor vasculature we studied four FHT-derivatives: NOTA-FHT, NOTA-(FHT)2, NOTA-PEG-FHT, and NOTA-PEG-(FHT)2. These peptide analogs were synthesized, labeled with the PET radionuclide (64)Cu, and characterized side-by-side with small animal PET and computed tomography imaging (microPET/CT) at 1 h, 4 h, and 24 h post injection in a subcutaneous Lewis lung carcinoma (LLC) tumor model. Because of its excellent in vivo kinetic properties and high tumor-to-background ratio, the (64)Cu-NOTA FHT radiopeptide was selected for more detailed evaluation. Blocking studies with excess of unlabeled peptide showed specific and peptide mediated (64)Cu-NOTA-FHT tumor uptake. Biodistribution experiments in the same tumor model confirmed microPET/CT imaging results. Human radiation absorbed dose extrapolated from rodent biodistribution of (64)Cu-NOTA-FHT revealed favorable dosimetry profile. The findings from this investigation warrant further development of (64)Cu-NOTA FHT as a potential targeted diagnostic radiopharmaceutical for PET imaging of aggressive tumor vasculature. PMID- 26839955 TI - Continental Refugium in the Mongolian Plateau during Quaternary Glacial Oscillations: Phylogeography and Niche Modelling of the Endemic Desert Hamster, Phodopus roborovskii. AB - The Mongolian Plateau (MP), which is situated in the interior of Asia and possesses a typical continental climate, experienced harsh climatic conditions during the Quaternary glacial fluctuations. Although these events likely had huge impacts on the local animal populations, the current effects have hardly been explored. To investigate whether the MP supported a refugium along an oceanic continental gradient (ROCG), and whether this refugium was glacial or interglacial, we investigated the demographic and phylogeographic history of an endemic mammal species, the desert hamster Phodopus roborovskii. We reconstructed the demographic variation, the phylogeographic diffusion, and modelled the potential habitat during historical periods. The genetic diversity in the MP was the highest among all the localities, and the MP was a suitable habitat throughout the modelled historical periods. A phylogeographic diffusion analysis emphasized the importance of the MP as the centre of origin, preservation and spread for P. roborovskii. The homogeneous landscape provided the opportunity for a wide gene flow, which resulted in low resolution of the phylogenetic relationships. Moreover, P. roborovskii was favoured by the interglacial condition, with both its demographical and geographical ranges expanded within the interglacial periods. The range variation from the Last Glacial Maximum to the current condition reflects a distinct longitudinal shift, while both ranges largely contracted from that of the Last Interglacial. Our results support that the MP served as a refugium and spread centre for P. roborovskii during the Quaternary climate fluctuations. The interglacial expansion and the longitudinal shifts highlighted the important effects of precipitations on the distribution range of species adapted to arid and semi-arid during glacial oscillations. PMID- 26839956 TI - Alloyed 2D Metal-Semiconductor Atomic Layer Junctions. AB - Heterostructures of compositionally and electronically variant two-dimensional (2D) atomic layers are viable building blocks for ultrathin optoelectronic devices. We show that the composition of interfacial transition region between semiconducting WSe2 atomic layer channels and metallic NbSe2 contact layers can be engineered through interfacial doping with Nb atoms. WxNb1-xSe2 interfacial regions considerably lower the potential barrier height of the junction, significantly improving the performance of the corresponding WSe2-based field effect transistor devices. The creation of such alloyed 2D junctions between dissimilar atomic layer domains could be the most important factor in controlling the electronic properties of 2D junctions and the design and fabrication of 2D atomic layer devices. PMID- 26839957 TI - Sex-Specific Audience Effect in the Context of Mate Choice in Zebra Finches. AB - Animals observing conspecifics during mate choice can gain additional information about potential mates. However, the presence of an observer, if detected by the observed individuals, can influence the nature of the behavior of the observed individuals, called audience effect. In zebra finches (Taeniopygia guttata castanotis), domesticated males show an audience effect during mate choice. However, whether male and female descendants of the wild form show an audience effect during mate choice is unknown. Therefore, we conducted an experiment where male and female focal birds could choose between two distinctive phenotypes of the opposite sex, an artificially adorned stimulus bird with a red feather on the forehead and an unadorned stimulus bird, two times consecutively, once without an audience and once with an audience bird (same sex as test bird). Males showed an audience effect when an audience male was present and spent more time with adorned and less time with unadorned females compared to when there was no audience present. The change in time spent with the respective stimulus females was positively correlated with the time that the audience male spent in front of its cage close to the focal male. Females showed no change in mate choice when an audience female was present, but their motivation to associate with both stimulus males decreased. In a control for mate-choice consistency there was no audience in either test. Here, both focal females and focal males chose consistently without a change in choosing motivation. Our results showed that there is an audience effect on mate choice in zebra finches and that the response to a same sex audience was sex-specific. PMID- 26839958 TI - Conditional Deletion of Fgfr1 in the Proximal and Distal Tubule Identifies Distinct Roles in Phosphate and Calcium Transport. AB - A postnatal role of fibroblast growth factor receptor-1 (FGFR1) in the kidney is suggested by its binding to alpha-Klotho to form an obligate receptor for the hormone fibroblast growth factor-23 (FGF-23). FGFR1 is expressed in both the proximal and distal renal tubular segments, but its tubular specific functions are unclear. In this study, we crossed Fgfr1flox/flox mice with either gamma glutamyltransferase-Cre (gammaGT-Cre) or kidney specific-Cre (Ksp-Cre) mice to selectively create proximal tubule (PT) and distal tubule (DT) Fgfr1 conditional knockout mice (designated Fgfr1PT-cKO and Fgfr1DT-cKO, respectively). Fgfr1PT-cKO mice exhibited an increase in sodium-dependent phosphate co-transporter expression, hyperphosphatemia, and refractoriness to the phosphaturic actions of FGF-23, consistent with a direct role of FGFR1 in mediating the proximal tubular phosphate responses to FGF-23. In contrast, Fgfr1DT-cKO mice unexpectedly developed hypercalciuria, secondary elevations of parathyroid hormone (PTH), hypophosphatemia and enhanced urinary phosphate excretion. Fgfr1PT-cKO mice also developed a curly tail/spina bifida-like skeletal phenotype, whereas Fgfr1DT-cKO mice developed renal tubular micro-calcifications and reductions in cortical bone thickness. Thus, FGFR1 has dual functions to directly regulate proximal and distal tubule phosphate and calcium reabsorption, indicating a physiological role of FGFR1 signaling in both phosphate and calcium homeostasis. PMID- 26839959 TI - Revisiting the Life Cycle of Dung Fungi, Including Sordaria fimicola. AB - Dung fungi, such as Sordaria fimicola, generally reproduce sexually with ascospores discharged from mammalian dung after passage through herbivores. Their life cycle is thought to be obligate to dung, and thus their ascospores in Quaternary sediments have been interpreted as evidence of past mammalian herbivore activity. Reports of dung fungi as endophytes would seem to challenge the view that they are obligate to dung. However, endophyte status is controversial because surface-sterilization protocols could fail to kill dung fungus ascospores stuck to the plant surface. Thus, we first tested the ability of representative isolates of three common genera of dung fungi to affect plant growth and fecundity given that significant effects on plant fitness could not result from ascospores merely stuck to the plant surface. Isolates of S. fimicola, Preussia sp., and Sporormiella sp. reduced growth and fecundity of two of three populations of Bromus tectorum, the host from which they had been isolated. In further work with S. fimicola we showed that inoculations of roots of B. tectorum led to some colonization of aboveground tissues. The same isolate of S. fimicola reproduced sexually on inoculated host plant tissues as well as in dung after passage through sheep, thus demonstrating a facultative rather than an obligate life cycle. Finally, plants inoculated with S. fimicola were not preferred by sheep; preference had been expected if the fungus were obligate to dung. Overall, these findings make us question the assumption that these fungi are obligate to dung. PMID- 26839960 TI - MorphoTester: An Open Source Application for Morphological Topographic Analysis. AB - The increased prevalence and affordability of 3D scanning technology is beginning to have significant effects on the research questions and approaches available for studies of morphology. As the current trend of larger and more precise 3D datasets is unlikely to slow in the future, there is a need for efficient and capable tools for high-throughput quantitative analysis of biological shape. The promise and the challenge of implementing relatively automated methods for characterizing surface shape can be seen in the example of dental topographic analysis. Dental topographic analysis comprises a suite of techniques for quantifying tooth surfaces and component features. Topographic techniques have provided insight on mammalian molar form-function relationships and these methods could be applied to address other topics and questions. At the same time implementing multiple complementary topographic methods can have high time and labor costs, and comparability of data formats and approaches is difficult to predict. To address these challenges I present MorphoTester, an open source application for visualizing and quantifying topography from 3D triangulated polygon meshes. This application is Python-based and is free to use. MorphoTester implements three commonly used dental topographic metrics-Dirichlet normal energy, relief index, and orientation patch count rotated (OPCR). Previous OPCR algorithms have used raster-based grid data, which is not directly interchangeable with vector-based triangulated polygon meshes. A 3D-OPCR algorithm is provided here for quantifying complexity from polygon meshes. The efficacy of this metric is tested in a sample of mandibular second molars belonging to four species of cercopithecoid primates. Results suggest that 3D OPCR is at least as effective for quantifying complexity as previous approaches, and may be more effective due to finer resolution of surface data considered here. MorphoTester represents an advancement in the automated quantification of morphology, and can be modified to adapt to future needs and priorities. PMID- 26839961 TI - Cellular Retinoic Acid Binding Protein 2 Is Strikingly Downregulated in Human Esophageal Squamous Cell Carcinoma and Functions as a Tumor Suppressor. AB - Esophageal squamous cell carcinoma (ESCC) is the predominant pathotype of esophageal carcinoma (EC) in China, especially in Henan province, with poor prognosis and limited 5-year survival rate. Cellular retinoic acid binding protein 2 (CRABP2) is a member of the retinoic acid (RA) and lipocalin/cytosolic fatty-acid binding protein family and plays a completely contrary role in tumorigenesis through the retinoid signaling pathway, depending on the nuclear RA receptors (RAR) and PPARbeta/delta receptors. Presently, the biological role of CRABP2 in the development of ESCC has never been reported. Here, we firstly evaluated the expression of CRABP2 at both mRNA and protein levels and showed that it was remarkably downregulated in clinical ESCC tissues and closely correlated with the occurrence position, pathology, TNM stage, size, infiltration depth and cell differentiation of the tumor. Additionally, the biological function assays demonstrated that CRABP2 acted as a tumor suppressor in esophageal squamous carcinogenesis by significantly inhibiting cell growth, inducing cell apoptosis and blocking cell metastasis both in vitro and in vivo. All in all, our finding simplicate that CRABP2 is possibly an efficient molecular marker for diagnosing and predicting the development of ESCC. PMID- 26839962 TI - Reconfiguration of the small intestine and diabetes remitting effects of Roux-en Y gastric bypass surgery. AB - PURPOSE OF REVIEW: Alterations in small intestinal physiology are proposed to play a causative role in the beneficial impact of Roux-en-Y gastric bypass on type 2 diabetes mellitus. The present article describes the key proposed mechanisms implicated with an emphasis on some of the newer findings in the field. RECENT FINDINGS: Augmented incretin and diminished anti-incretin effects postsurgery are explored and a model proposed that reconciles the hindgut and foregut hypotheses of improved glycaemic control as being complementary rather than mutually exclusive. Synthesis of recent findings on postbypass changes in intestinal glucose handling then follows. Finally an updated view of the role of distal bile diversion and changes in the microbiota on enteroendocrine signalling is presented. SUMMARY: A series of nonmutually exclusive changes in small intestinal physiology likely make a significant contribution to improved glycaemic control postgastric bypass. Longitudinal data indicate that these effects do not translate into a long-term cure. A number of surgery-induced changes, however, are amenable to device-based and pharmacology-based mimicry, and this is an area for prioritization of future research focus. PMID- 26839963 TI - Exercise, fitness, and the gut. AB - PURPOSE OF REVIEW: Exercise and gut symptomatology have long been connected. The possibility that regular exercise fosters intestinal health and function has been somewhat overlooked in the scientific literature. In this review, we summarize current knowledge and discuss a selection of recent, relevant, and innovative studies, hypotheses and reviews that elucidate a complex topic. RECENT FINDINGS: The multiorgan benefits of regular exercise are extensive. When taken in moderation, these benefits transcend improved cardio-respiratory fitness and likely reach the gut in a metabolic, immunological, neural, and microbial manner. This is applicable in both health and disease. However, further work is required to provide safe, effective recommendations on physical activity in specific gastrointestinal conditions. SUMMARY: Challenging methodology investigating the relationship between exercise and gut health should not deter from exploring exercise in the promotion of gastrointestinal health. PMID- 26839964 TI - Emerging issues in the medical management of Crohn's disease. AB - PURPOSE OF REVIEW: This article describes why this review is timely and relevant. The medical management of Crohn's disease is complex, and is changing rapidly with the introduction of novel therapeutic agents and management strategies. RECENT FINDINGS: We have summarized and synthesized up-to-date evidence and opinion on the proper role and composition of combined immunosuppressive therapy in the management of Crohn's disease, the optimal time for introduction of immunomodulator and/or biologic therapies, and the benefits of therapeutic drug monitoring for biologic therapies. We also discuss the evidence supporting the benefits of the novel agents vedolizumab and ustekinumab, and discuss where they will fit into the therapeutic landscape. SUMMARY: The review will provide evidence to support decision making in patients with Crohn's disease requiring biologic and/or immunomodulator therapy. PMID- 26839966 TI - Improved Segmented All-Electron Relativistically Contracted Basis Sets for the Lanthanides. AB - Improved versions of the segmented all-electron relativistically contracted (SARC) basis sets for the lanthanides are presented. The second-generation SARC2 basis sets maintain efficient construction of their predecessors and their individual adaptation to the DKH2 and ZORA Hamiltonians, but feature exponents optimized with a completely new orbital shape fitting procedure and a slightly expanded f space that results in sizable improvement in CASSCF energies and in significantly more accurate prediction of spin-orbit coupling parameters. Additionally, an extended set of polarization/correlation functions is constructed that is appropriate for multireference correlated calculations and new auxiliary basis sets for use in resolution-of-identity (density-fitting) approximations in combination with both DFT and wave function based treatments. Thus, the SARC2 basis sets extend the applicability of the first-generation DFT oriented basis sets to routine all-electron wave function-based treatments of lanthanide complexes. The new basis sets are benchmarked with respect to excitation energies, radial distribution functions, optimized geometries, orbital eigenvalues, ionization potentials, and spin-orbit coupling parameters of lanthanide systems and are shown to be suitable for the description of magnetic and spectroscopic properties using both DFT and multireference wave function based methods. PMID- 26839965 TI - Transcriptome Analysis of Targeted Mouse Mutations Reveals the Topography of Local Changes in Gene Expression. AB - The unintended consequences of gene targeting in mouse models have not been thoroughly studied and a more systematic analysis is needed to understand the frequency and characteristics of off-target effects. Using RNA-seq, we evaluated targeted and neighboring gene expression in tissues from 44 homozygous mutants compared with C57BL/6N control mice. Two allele types were evaluated: 15 targeted trap mutations (TRAP); and 29 deletion alleles (DEL), usually a deletion between the translational start and the 3' UTR. Both targeting strategies insert a bacterial beta-galactosidase reporter (LacZ) and a neomycin resistance selection cassette. Evaluating transcription of genes in +/- 500 kb of flanking DNA around the targeted gene, we found up-regulated genes more frequently around DEL compared with TRAP alleles, however the frequency of alleles with local down regulated genes flanking DEL and TRAP targets was similar. Down-regulated genes around both DEL and TRAP targets were found at a higher frequency than expected from a genome-wide survey. However, only around DEL targets were up-regulated genes found with a significantly higher frequency compared with genome-wide sampling. Transcriptome analysis confirms targeting in 97% of DEL alleles, but in only 47% of TRAP alleles probably due to non-functional splice variants, and some splicing around the gene trap. Local effects on gene expression are likely due to a number of factors including compensatory regulation, loss or disruption of intragenic regulatory elements, the exogenous promoter in the neo selection cassette, removal of insulating DNA in the DEL mutants, and local silencing due to disruption of normal chromatin organization or presence of exogenous DNA. An understanding of local position effects is important for understanding and interpreting any phenotype attributed to targeted gene mutations, or to spontaneous indels. PMID- 26839967 TI - A Vulnerability Assessment of Fish and Invertebrates to Climate Change on the Northeast U.S. Continental Shelf. AB - Climate change and decadal variability are impacting marine fish and invertebrate species worldwide and these impacts will continue for the foreseeable future. Quantitative approaches have been developed to examine climate impacts on productivity, abundance, and distribution of various marine fish and invertebrate species. However, it is difficult to apply these approaches to large numbers of species owing to the lack of mechanistic understanding sufficient for quantitative analyses, as well as the lack of scientific infrastructure to support these more detailed studies. Vulnerability assessments provide a framework for evaluating climate impacts over a broad range of species with existing information. These methods combine the exposure of a species to a stressor (climate change and decadal variability) and the sensitivity of species to the stressor. These two components are then combined to estimate an overall vulnerability. Quantitative data are used when available, but qualitative information and expert opinion are used when quantitative data is lacking. Here we conduct a climate vulnerability assessment on 82 fish and invertebrate species in the Northeast U.S. Shelf including exploited, forage, and protected species. We define climate vulnerability as the extent to which abundance or productivity of a species in the region could be impacted by climate change and decadal variability. We find that the overall climate vulnerability is high to very high for approximately half the species assessed; diadromous and benthic invertebrate species exhibit the greatest vulnerability. In addition, the majority of species included in the assessment have a high potential for a change in distribution in response to projected changes in climate. Negative effects of climate change are expected for approximately half of the species assessed, but some species are expected to be positively affected (e.g., increase in productivity or move into the region). These results will inform research and management activities related to understanding and adapting marine fisheries management and conservation to climate change and decadal variability. PMID- 26839968 TI - Point-of-Care Warfarin Monitoring in the ROCKET AF Trial. PMID- 26839971 TI - Correction to "Comprehensive Synthesis of Monohydroxy-Cucurbit[n]urils (n = 5, 6, 7, 8): High Purity and High Conversions". PMID- 26839969 TI - Paeonia lactiflora Enhances the Adhesion of Trophoblast to the Endometrium via Induction of Leukemia Inhibitory Factor Expression. AB - In the present study, we investigated the role of Paeonia lactiflora Pall. extract on embryo implantation in vitro and in vivo. A polysaccharides depleted water extract of P. lactiflora (PL-PP) increased LIF expression in human endometrial Ishikawa cells at non-cytotoxic doses. PL-PP significantly increased the adhesion of the human trophectoderm-derived JAr spheroids to endometrial Ishikawa cells. PL-PP-induced LIF expression was decreased in the presence of a p38 kinase inhibitor SB203580 and an MEK/ERK inhibitor U0126. Furthermore, endometrial LIF knockdown by shRNA reduced the expression of integrins beta3 and beta5 and adhesion of JAr spheroids to Ishikawa cells. In vivo administration of PL-PP restored the implantation of mouse blastocysts in a mifepristone-induced implantation failure mice model. Our results demonstrate that PL-PP increases LIF expression via the p38 and MEK/ERK pathways and favors trophoblast adhesion to endometrial cells. PMID- 26839970 TI - Co-Occurrence of Two Allelic Variants of CYP51 in Erysiphe necator and Their Correlation with Over-Expression for DMI Resistance. AB - Demethylation inhibitors (DMIs) have been an important tool in the management of grapevine powdery mildew caused by Erysiphe necator. Long-term, intensive use of DMIs has resulted in reduced sensitivity in field populations. To further characterize DMI resistance and understand resistance mechanisms in this pathogen, we investigated the cyp51 sequence of 24 single-spored isolates from Virginia and surrounding states and analyzed gene expression in isolates representing a wide range of sensitivity. Two cyp51 alleles were found with respect to the 136th codon of the predicted EnCYP51 sequence: the wild-type (TAT) and the mutant (TTT), which results in the known Y136F amino acid change. Some isolates possessed both alleles, demonstrating gene duplication or increased gene copy number and possibly a requirement for at least one mutant copy of CYP51 for resistance. Cyp51 was over-expressed 1.4- to 19-fold in Y136F-mutant isolates. However, the Y136F mutation was absent in one isolate with moderate to high resistance factor. Two additional synonymous mutations were detected as well, one of which, A1119C was present only in isolates with high cyp51 expression. Overall, our results indicate that at least two mechanisms, cyp51 over-expression and the known target-site mutation in CYP51, contribute to resistance in E. necator, and may be working in conjunction with each other. PMID- 26839972 TI - Thermally Released Arsenic in Porewater from Sediments in the Cold Lake Area of Alberta, Canada. AB - Elevated arsenic (As) in aquifers in close proximity to in situ oil sands extraction in the Cold Lake area, Alberta, Canada is attributed to high temperature steam (~200 degrees C) injected into oil sands deposits to liquefy bitumen. Heat propagated from hot injection wells alters physicochemical properties of the surrounding sediments and associated porewater. Seven sediments from four different cores drilled up to ~300 m depth collected from different locations in the area were used to study the thermal effect (~200 degrees C) on As distribution in the sediments and its release into porewater. Sediments were moistened with synthetic aquifer or deionized water according to the moisture regimes present in aquitard, aquifer and fractured zones. Heat application greatly released As in the porewater (500-5200 and 1200-6600 MUg L(-1)) from aquifer and fractured sediments, respectively. Mass balance of As chemical fractionation showed that ~89-100% of As in porewater was released from exchangeable and specifically adsorbed As in the sediments. Heat application also altered As distribution in the sediments releasing As from exchange surfaces and amorphous Fe oxides to soluble As fraction. The results provide great insight into As release mechanisms warranting development of strategies to mitigate groundwater As contamination during industrial operation. PMID- 26839973 TI - Fat is a realist's issue. PMID- 26839974 TI - Spectral Signatures of Ultrafast Spin Crossover in Single Crystal [Fe(II)(bpy)3](PF6)2. AB - Solvated iron(II)-tris(bipyridine) ([Fe(II)(bpy)3](2+)) has been extensively studied with regard to the spin crossover (SCO) phenomenon. Herein, the ultrafast spin transition dynamics of single crystal [Fe(II)(bpy)3](PF6)2 was characterized for the first time using femtosecond transient absorption (TA) spectroscopy. The single crystal environment is of interest for experiments that probe the nuclear motions involved in the SCO transition, such as femtosecond X-ray and electron diffraction. We found that the TA at early times is very similar to what has been reported in solvated [Fe(II)(bpy)3](2+), whereas the later dynamics are perturbed in the crystal environment. The lifetime of the high-spin state is found to be much shorter (100 ps) than in solution due to chemical pressure exerted by the lattice. Oscillatory behavior was observed on both time scales. Our results show that single crystal [Fe(II)(bpy)3](PF6)2 serves as an excellent model system for localized molecular spin transitions. PMID- 26839975 TI - Magnetic assembly of 3D cell clusters: visualizing the formation of an engineered tissue. AB - OBJECTIVES: Contactless magnetic assembly of cells into 3D clusters has been proposed as a novel means for 3D tissue culture that eliminates the need for artificial scaffolds. However, thus far its efficacy has only been studied by comparing expression levels of generic proteins. Here, it has been evaluated by visualizing the evolution of cell clusters assembled by magnetic forces, to examine their resemblance to in vivo tissues. MATERIALS AND METHODS: Cells were labeled with magnetic nanoparticles, then assembled into 3D clusters using magnetic force. Scanning electron microscopy was used to image intercellular interactions and morphological features of the clusters. RESULTS: When cells were held together by magnetic forces for a single day, they formed intercellular contacts through extracellular fibers. These kept the clusters intact once the magnetic forces were removed, thus serving the primary function of scaffolds. The cells self-organized into constructs consistent with the corresponding tissues in vivo. Epithelial cells formed sheets while fibroblasts formed spheroids and exhibited position-dependent morphological heterogeneity. Cells on the periphery of a cluster were flattened while those within were spheroidal, a well-known characteristic of connective tissues in vivo. CONCLUSIONS: Cells assembled by magnetic forces presented visual features representative of their in vivo states but largely absent in monolayers. This established the efficacy of contactless assembly as a means to fabricate in vitro tissue models. PMID- 26839976 TI - Risk Adjustment Tools for Learning Health Systems: A Comparison of DxCG and CMS HCC V21. AB - OBJECTIVE: To compare risk scores computed by DxCG (Verisk) and Centers for Medicare and Medicaid Services (CMS) V21. RESEARCH DESIGN: Analysis of administrative data from the Department of Veterans Affairs (VA) for fiscal years 2010 and 2011. STUDY DESIGN: We regressed total annual VA costs on predicted risk scores. Model fit was judged by R-squared, root mean squared error, mean absolute error, and Hosmer-Lemeshow goodness-of-fit tests. Recalibrated models were tested using split samples with pharmacy data. DATA COLLECTION: We created six analytical files: a random sample (n = 2 million), high cost users (n = 261,487), users over age 75 (n = 644,524), mental health and substance use users (n = 830,832), multimorbid users (n = 817,951), and low-risk users (n = 78,032). PRINCIPAL FINDINGS: The DxCG Medicaid with pharmacy risk score yielded substantial gains in fit over the V21 model. Recalibrating the V21 model using VA pharmacy data-generated risk scores with similar fit statistics to the DxCG risk scores. CONCLUSIONS: Although the CMS V21 and DxCG prospective risk scores were similar, the DxCG model with pharmacy data offered improved fit over V21. However, health care systems, such as the VA, can recalibrate the V21 model with additional variables to develop a tailored risk score that compares favorably to the DxCG models. PMID- 26839978 TI - Re: Prostate-specific antigen-based prostate cancer screening: Past and future. PMID- 26839977 TI - Standardized letters of recommendation and successful match into otolaryngology. AB - OBJECTIVES/HYPOTHESIS: Historically, narrative letters of recommendation have been utilized in the selection of applicants for otolaryngology residency programs. In the last two application cycles, our specialty adopted a standardized letter of recommendation (SLOR). The intent was to decrease time burden for letter writers and to provide readers with an objective evaluation of applicants. The objective of this study was to determine attributes in the SLOR that correlate with matching into a residency program. STUDY DESIGN: We performed a retrospective study using SLOR, United States Medical Licensing Examination (USMLE) step 1 scores, and matched outcomes of applicants who applied to our institution for the 2013 and 2014 match cycle. METHODS: We included the following variables from the SLOR in the statistical analysis to determine which ones were associated with matching: patient care, medical knowledge, communication skills, procedural skills, research, initiative and drive, commitment to otolaryngology, commitment to academic medicine, match potential, and USMLE1 scores. RESULTS: We identified 532 applicants and 963 SLOR. In successful applicants, scores for patient care, medical knowledge, communication skills, initiative and drive, and match potential were statistically higher (P < 0.05). Scores for professionalism, procedural skills, research, commitment to otolaryngology, commitment to academic medicine, and USMLE step 1 scores were not higher among successfully matched applicants. CONCLUSION: Although SLOR can save time for letter writers and provide an objective description of applicants, the utility of individual domains within the SLOR is questionable. Additionally, it is concerning that applicants' professionalism and procedural skills are not correlated with matching in our specialty. LEVEL OF EVIDENCE: NA. Laryngoscope, 126:1071-1076, 2016. PMID- 26839979 TI - Effects of levosimendan on isolated human internal mammary artery and saphenous vein: concurrent use with conventional vasodilators. AB - Graft spasm is a common problem in coronary artery bypass grafting (CABG). In this study, we aimed to investigate the interaction of levosimendan, a novel inodilator, with vasodilator agents that are clinically used for the treatment of graft spasm and with endogenous vasoconstrictors that are thought to play a role in graft vasospasm, in human internal mammary artery (IMA) and saphenous vein (SV). Isolated human IMA and SV segments derived from patients undergoing CABG were suspended in an organ bath. Responses to cumulative concentrations of noradrenaline (NA), serotonin (5-HT), papaverine, nitroglycerin (NG), and diltiazem were recorded before and after 10(-5) m levosimendan incubation (30 min). In addition, cumulative levosimendan responses were taken in vessels precontracted with NA or 5-HT. 10(-5) m levosimendan reduced NA Emax and sensitivity in IMA and SV, and 5-HT Emax responses in IMA. Moreover, levosimendan caused concentration-dependent relaxation in both grafts. Papaverine Emax or sensitivity was not altered by levosimendan neither in IMA nor in SV. Levosimendan diminished NG sensitivity in IMA and Emax responses in SV and decreased diltiazem Emax responses both in IMA and SV. Our results suggest that levosimendan may be used alone for prevention or treatment of graft spasm in IMA or in combination with papaverine in IMA and SV grafts. However, as concurrent administration with diltiazem or NG causes a reduction in relaxation in vitro, we suggest caution should be exercised when using levosimendan in combination with these agents. PMID- 26839981 TI - Mutation in the gene encoding 1-aminocyclopropane-1-carboxylate synthase 4 (CitACS4) led to andromonoecy in watermelon. AB - Although it has been reported previously that ethylene plays a critical role in sex determination in cucurbit species, how the andromonoecy that carries both the male and hermaphroditic flowers is determined in watermelon is still unknown. Here we showed that the watermelon gene 1-aminocyclopropane-1-carboxylate synthase 4 (CitACS4), expressed specifically in carpel primordia, determines the andromonoecy in watermelon. Among four single nucleotide polymorphism (SNPs) and one InDel identified in the coding region of CitACS4, the C364W mutation located in the conserved box 6 was co-segregated with andromonoecy. Enzymatic analyses showed that the C364W mutation caused a reduced activity in CitACS4. We believe that the reduced CitACS4 activity may hamper the programmed cell death in stamen primordia, leading to the formation of hermaphroditic flowers. PMID- 26839980 TI - Diabetic gastroparesis alters the biomagnetic signature of the gastric slow wave. AB - BACKGROUND: Gastroparesis is characterized by delayed gastric emptying without mechanical obstruction, but remains difficult to diagnose and distinguish from other gastrointestinal (GI) disorders. Gastroparesis affects the gastric slow wave, but non-invasive assessment has been limited to the electrogastrogram (EGG), which reliably characterizes temporal dynamics but does not provide spatial information. METHODS: We measured gastric slow wave parameters from the EGG and magnetogastrogram (MGG) in patients with gastroparesis and in healthy controls. In addition to dominant frequency (DF) and percentage power distribution (PPD), we measured the propagation velocity from MGG spatiotemporal patterns and the percentage of slow wave coupling (%SWC) from EGG. KEY RESULTS: No significant difference in DF was found between patients and controls. Gastroparesis patients had lower percentages of normogastric frequencies (60 +/- 6% vs 78 +/- 4%, p < 0.05), and higher brady (9 +/- 2% vs 2 +/- 1%, p < 0.05) and tachygastric (31 +/- 2% vs 19 +/- 1%, p < 0.05) frequency content postprandial, indicative of uncoupling. Propagation patterns were substantially different in patients and longitudinal propagation velocity was retrograde at 4.3 +/- 2.9 mm/s vs anterograde at 7.4 +/- 1.0 mm/s for controls (p < 0.01). No difference was found in %SWC from EGG. CONCLUSIONS & INFERENCES: Gastric slow wave parameters obtained from MGG recordings distinguish gastroparesis patients from controls. Assessment of slow wave propagation may prove critical to characterization of underlying disease processes. Future studies should determine pathologic indicators from MGG associated with other functional gastric disorders, and whether multichannel EGG with appropriate signal processing also reveals pathology. PMID- 26839982 TI - Rounding Up the Usual Suspects: Nonsustained Ventricular Tachycardia and Sustained Left Ventricular Dysfunction as Risk Factors for Sudden Death in Isolated AV Block. PMID- 26839984 TI - Dynamic changes of B-cell compartments in kidney transplantation: lack of transitional B cells is associated with allograft rejection. AB - B cells play an important role in the immune responses which affect the outcomes of kidney allografts. Dynamic changes of B-cell compartments in clinical kidney transplantation are still poorly understood. B-cell subsets were prospectively monitored using flow cytometry for 1 year in 98 kidney transplant recipients. Data were correlated with immunosuppression and clinical outcomes. An increase in the total population of B lymphocytes was observed during the first week after transplantation. The level of IgM(high) CD38(high) CD24(high) transitional B cells reduced significantly up until the third month, with partial repopulation in the first year. Lower numbers of transitional B cells in the third month were associated with higher risk of graft rejection. IgM(+) IgD(+) CD27(-) naive B cells did not change within follow-up. IgM(+) CD27(+) nonswitched memory B cells and IgM(-) CD27(+) switched memory B cells increased on post-operative day 7. IgM(-) CD38(high) CD27(high) plasmablasts showed similar kinetics during the first post-transplant year, similar to transitional B cells. In conclusion, sensitized kidney transplant recipients as well as those with either acute or chronic rejection within the first post-transplant year exhibited lower levels of transitional B cells. Therefore, these data further support the hypothesis that transitional B cells have a protective role in kidney transplantation. PMID- 26839983 TI - International recommendation for a comprehensive neuropathologic workup of epilepsy surgery brain tissue: A consensus Task Force report from the ILAE Commission on Diagnostic Methods. AB - Epilepsy surgery is an effective treatment in many patients with drug-resistant focal epilepsies. An early decision for surgical therapy is facilitated by a magnetic resonance imaging (MRI)-visible brain lesion congruent with the electrophysiologically abnormal brain region. Recent advances in the pathologic diagnosis and classification of epileptogenic brain lesions are helpful for clinical correlation, outcome stratification, and patient management. However, application of international consensus classification systems to common epileptic pathologies (e.g., focal cortical dysplasia [FCD] and hippocampal sclerosis [HS]) necessitates standardized protocols for neuropathologic workup of epilepsy surgery specimens. To this end, the Task Force of Neuropathology from the International League Against Epilepsy (ILAE) Commission on Diagnostic Methods developed a consensus standard operational procedure for tissue inspection, distribution, and processing. The aims are to provide a systematic framework for histopathologic workup, meeting minimal standards and maximizing current and future opportunities for morphofunctional correlations and molecular studies for both clinical care and research. Whenever feasible, anatomically intact surgical specimens are desirable to enable systematic analysis in selective hippocampectomies, temporal lobe resections, and lesional or nonlesional neocortical samples. Correct orientation of sample and the sample's relation to neurophysiologically aberrant sites requires good communication between pathology and neurosurgical teams. Systematic tissue sampling of 5-mm slabs along a defined anatomic axis and application of a limited immunohistochemical panel will ensure a reliable differential diagnosis of main pathologies encountered in epilepsy surgery. PMID- 26839985 TI - Validation of the Brief Pain Inventory in Patients With Low Back Pain. AB - STUDY DESIGN: Cross-sectional psychometric testing in a sample of patients with low back pain (LBP). OBJECTIVE: The aim of this study was to examine the construct, convergent, and discriminative validity of the Brief Pain Inventory (BPI) in patients with LBP. SUMMARY OF BACKGROUND DATA: The BPI was originally developed to assess cancer pain. Currently, it is commonly used to measure pain intensity and pain interference in patients with malignant or nonmalignant pain. However, the two-factor construct of the BPI has not been confirmed in an LBP population. METHODS: A total of 271 patients with LBP completed the BPI and Oswestry Disability Index (ODI) questionnaires. The construct validity (i.e., the two-factor structure: intensity scale and interference scale) of the BPI was determined by confirmatory factor analysis. The convergent validity was investigated by examining the relationships between the BPI scales and the ODI scores. The discriminative validity of the BPI was examined by testing if the BPI scale scores differed among groups of patients with different levels of disability. RESULTS: Confirmatory factor analysis partially confirmed the two factor structure of the BPI for use in patients with LBP. The convergent validity of the BPI was supported by its moderate correlation between the interference scale and the ODI score (rho = 0.66, P < 0.001), and by its low correlation between the intensity scale and the ODI score (rho = 0.39, P < 0.001). Finally, both the intensity scale and the interference scale discriminated among patients with varying levels of disability (both P < 0.001). CONCLUSION: The two-factor structure of the BPI as a measure of pain intensity and interference in patients with LBP was partially confirmed. Furthermore, our results lend some supports to the convergent validity and discriminative validity of the BPI. LEVEL OF EVIDENCE: N/A. PMID- 26839986 TI - A Review of Minimally Invasive Procedures for the Treatment of Adult Spinal Deformity. AB - STUDY DESIGN: Literature review. OBJECTIVE: To review the literature evaluating the role of minimally invasive (MIS) techniques in the operative treatment of adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: MIS techniques have become important tools in the armamentarium of spinal deformity surgeons as a means of achieving coronal and sagittal plane correction, while minimizing the complications of open deformity surgery. The literature suggests that MIS techniques are associated with certain limitations, and to date, determining which patients are candidates for MIS deformity correction is largely based on surgeon experience. METHODS: A systematic literature review was performed using the PubMed-National Library of Medicine/National Institute of Health databases. All studies describing the use of MIS techniques in ASD surgery were included for review. RESULTS: A total of 39 articles were included in the review. All studies were specifically designed to demonstrate radiographic and clinical outcomes of MIS techniques. Thirty articles were specific to MIS techniques as they relate to ASD surgery, whereas six articles were designed to describe details of various MIS techniques, and three articles were related to general principles of corrective surgery for ASD. CONCLUSION: The literature has demonstrated that MIS techniques are effective in achieving radiographic correction after surgery for ASD, while reducing complications compared with traditional open surgery. However, MIS techniques have limitations and may not be as effective as open surgery for severe and/or fixed sagittal and coronal plane deformity. Therefore, selecting patients for stand-alone MIS versus circumferential (cMIS) versus hybrid MIS (hybMIS) is critically important. The MIS spinal deformity surgery algorithm was designed to address this topic. Further studies are required to better elucidate the role and limitations of MIS techniques in patient undergoing corrective surgery for ASD. LEVEL OF EVIDENCE: N/A. PMID- 26839987 TI - Breaking Through the "Glass Ceiling" of Minimally Invasive Spine Surgery. PMID- 26839988 TI - The Impact of Resident Involvement in Elective Posterior Cervical Fusion. AB - STUDY DESIGN: Retrospective study of prospectively collected data OBJECTIVE.: The aim of this study was to assess the impact of resident surgeon involvement on patient outcomes following posterior cervical fusion (PCF) surgery. SUMMARY OF BACKGROUND DATA: Recently, there has been a significant uptrend in the number of PCF performed in the United States. Prior studies have investigated patient outcomes after cervical arthrodesis. Despite the heightened concern for patient safety and quality improvement, the data on the safety of resident participation in PCF is sparse. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) was examined from 2005 to 2012. Current Procedural Terminology codes were used to query the database for adults (>=18 years) who underwent PCF. Multivariate logistic regression models were employed on data adjusted by propensity scores to determine whether resident involvement was an independent predictor for the outcomes of interest. RESULTS: A total of 448 cases were assessed in NSQIP. Less than half of these cases involved residents (224, 43.1%). Resident involvement was found to be a significant predictor for blood transfusions [odds ratio (OR) = 1.7, confidence interval (CI) = 1.1-2.6, P = 0.010], length of stay of more than 5 days (OR = 1.6, CI = 1.0 2.6, P = 0.040), and operative time more than 4 hours (OR = 3.6, CI = 1.7-7.4, P = 0.0007). Other independent risk factors for prolonged length of stay included age 81 years or older versus 50 years or younger (OR = 4.7, CI = 1.7-12.6, P = 0.016) and diabetes (OR = 2.3, CI = 1.3-4.1, P = 0.006). In addition, multifusion was identified as a significant risk factor for extended operative time (OR = 1.8, CI = 1.1-2.9, P = 0.023). CONCLUSION: The present study used a large, nationwide sample to assess the impact of resident involvement in PCF. Resident participation was not associated with mortality, but had a minimal association with morbidity. LEVEL OF EVIDENCE: 3. PMID- 26839990 TI - Distraction Laminoplasty With Interlaminar Lumbar Instrumented Fusion (ILIF) for Lumbar Stenosis With or Without Grade 1 Spondylolisthesis: Technique and 2-Year Outcomes. AB - STUDY DESIGN: Prospective, nonrandomized cohort. OBJECTIVE: Describe the surgical technique and clinical outcome of distraction lumbar laminoplasty with allograft bone block augmentation and interlaminar lumbar instrumented fusion (ILIF) SUMMARY OF BACKGROUND DATA.: ILIF is a recently described technique that may offer a less invasive alternative to traditional posterior pedicle screw fixation for stabilization during posterior or posterolateral lumbar fusion after decompression for lumbar spinal stenosis. METHODS: Data from two sites of a prospective, multicenter clinical study is described in this report and includes 37 patients over age 40 with single-level degenerative disc disease between L1-2 and L4-5 with neurogenic claudication. Subjects were treated with lumbar decompression using a distraction laminoplasty procedure followed by insertion of a preshaped allograft bone block and interspinous stabilization with a fixation device. BMP-2 was not used. Follow-up clinical evaluation was performed at baseline and at 6 weeks, 3, 6, 12, and 24 months, including perioperative complications, visual analog pain score, Oswestry Disability Index, Zurich Claudication Questionnaire scores and return to activity and work. Radiographic evaluation of fusion and segmental and regional lumbar lordosis were performed to 2 years. RESULTS: Thirty-three patients (89%) of mean age 71 years (17% woman) met all follow-up criteria at 2 years. Levels treated were L4-5 (78.4%), L3-4 (16.2%), or L2-3 (5.4%). Thirty-two of 37 (86%) of patients had a grade-1 spondylolisthesis. Mean hospital length of stay (LOS) was 2 days. Complications included one dural tear, one new neuro deficit that resolved by 6 weeks, one implant failure, one seroma, and one case of cancer diagnosis. At 2 years, 67% had >2 cm improvement on visual analog pain score and 73% had >12.4% Oswestry Disability Index improvement. Symptom severity and physical function subset scores of Zurich Claudication Questionnaire improved by >0.5 cm in 76 and 73% of patients, respectively. At 2 years 94% of patients were off all narcotics and NSAIDS and 94% reported satisfaction with the procedure. Mean lumbar lordosis at baseline and 2 years was 53 +/- 14 degrees and 53 +/- 13 degrees , respectively. Seventy-two percent of subjects met strict fusion criterion of <3 degrees motion on flexion/extension XRAY and bridging bone; 97% met criteria for stability by independent surgeon evaluation. CONCLUSION: Distraction laminoplasty with allograft bone block augmentation and ILIF may provide a less-invasive alternative to traditional pedicle screw fixation after decompression and posterolateral fusion. The present study describes this technique, and demonstrates excellent clinical outcomes and an acceptable rate of radiographic fusion success. LEVEL OF EVIDENCE: NA. PMID- 26839989 TI - ISSLS Prize Winner: Consensus on the Clinical Diagnosis of Lumbar Spinal Stenosis: Results of an International Delphi Study. AB - STUDY DESIGN: Delphi. OBJECTIVE: The aim of this study was to obtain an expert consensus on which history factors are most important in the clinical diagnosis of lumbar spinal stenosis (LSS). SUMMARY OF BACKGROUND DATA: LSS is a poorly defined clinical syndrome. Criteria for defining LSS are needed and should be informed by the experience of expert clinicians. METHODS: Phase 1 (Delphi Items): 20 members of the International Taskforce on the Diagnosis and Management of LSS confirmed a list of 14 history items. An online survey was developed that permits specialists to express the logical order in which they consider the items, and the level of certainty ascertained from the questions. Phase 2 (Delphi Study) Round 1: Survey distributed to members of the International Society for the Study of the Lumbar Spine. Round 2: Meeting of 9 members of Taskforce where consensus was reached on a final list of 10 items. Round 3: Final survey was distributed internationally. Phase 3: Final Taskforce consensus meeting. RESULTS: A total of 279 clinicians from 29 different countries, with a mean of 19 (+/-SD: 12) years in practice participated. The six top items were "leg or buttock pain while walking," "flex forward to relieve symptoms," "feel relief when using a shopping cart or bicycle," "motor or sensory disturbance while walking," "normal and symmetric foot pulses," "lower extremity weakness," and "low back pain." Significant change in certainty ceased after six questions at 80% (P < .05). CONCLUSION: This is the first study to reach an international consensus on the clinical diagnosis of LSS, and suggests that within six questions clinicians are 80% certain of diagnosis. We propose a consensus-based set of "seven history items" that can act as a pragmatic criterion for defining LSS in both clinical and research settings, which in the long term may lead to more cost-effective treatment, improved health care utilization, and enhanced patient outcomes. LEVEL OF EVIDENCE: 2. PMID- 26839991 TI - Procedural Checklist for Retroperitoneal Transpsoas Minimally Invasive Lateral Interbody Fusion. AB - STUDY DESIGN: An expert opinion. OBJECTIVE: The aim of this study is to provide an overview of the surgical technique with an emphasis on complication avoidance techniques and to present a procedural checklist for the retroperitoneal transpsoas minimally invasive lateral approach. SUMMARY OF BACKGROUND DATA: Although the minimally invasive lateral interbody fusion has gained popularity in the past decade, complication rate variability remains in the literature, driven by inconsistent adherence to technique, neuromonitoring, and complication avoidance techniques. METHODS: The surgical and complication avoidance techniques for extreme lateral interbody fusion are presented in a stepwise fashion from the practice of an experienced lateral approach surgeon. RESULTS: The technical description and procedural checklist cover preoperative assessment, operating room setup, patient positioning, surgical procedure, and postoperative evaluation. CONCLUSION: A systematic approach through preoperative assessment, attention to surgical technique and intraoperative neuromonitoring, and a detailed postoperative evaluation are key to achieving the goal of lateral interbody fusion with minimization of procedural morbidity. LEVEL OF EVIDENCE: 5. PMID- 26839992 TI - Two-Year Comparative Outcomes of MIS Lateral and MIS Transforaminal Interbody Fusion in the Treatment of Degenerative Spondylolisthesis: Part II: Radiographic Findings. AB - STUDY DESIGN: Prospective, multicenter, institutional review board approved study with randomized and observational study arms. OBJECTIVE: The purpose of this study was to compare radiographic outcomes between minimally invasive transforaminal (MIS TLIF) or MIS lateral interbody fusion (XLIF) in the treatment of patients with low-grade degenerative spondylolisthesis with stenosis through 2 year postoperative. SUMMARY OF BACKGROUND DATA: Few reports exist comparing different MIS approaches directly in the treatment of similar pathology, as most studies report differences between MIS and open procedures. METHODS: A total of 55 patients undergoing surgical treatment for degenerative spondylolisthesis with spinal stenosis at one or two contiguous levels between L1 and L5 were enrolled. Twenty-nine patients were treated with XLIF and 26 patients were treated with MIS TLIF. RESULTS: Disc height was significantly improved from preoperative at all postoperative time points in both groups, though the XLIF group experienced less subsidence and resultant loss of disc height than the MIS TLIF group by 24-month postoperative (P = 0.002). Postoperative change in central canal area was statistically greater in the MIS TLIF compared with the XLIF group (43.1 mmvs. 4.1 mm, P = 0.028). At several postoperative time points, foraminal height and area on the ipsilateral side and foraminal height on the contralateral side to the approach were significantly increased postoperatively in the XLIF group, and the magnitude of ipsilateral height increase was greater than in the MIS TLIF cohort (P < 0.05).Using fusion criteria of <3 degrees range of motion and <3 mm translation on plain radiographs, 100% of patients in both groups were solidly fused at 24-month postoperative. Using computed tomography fusion criteria of presence of intervertebral bridging bone, 100% (32/32) of XLIF levels and 96% (25/26) of MIS TLIF levels were solidly bridged (P = 0.448). CONCLUSION: Different mechanisms of stenosis correction (direct vs. indirect) between the MIS TLIF and XLIF groups studied resulted in several significantly different radiographic characteristics. Despite these differences, both groups of patients experienced significant and maintained clinical improvements with high fusion rates at 2-year follow-up, suggesting that the mechanism of correction may not be critical and both MIS procedures are reasonable treatment options for degenerative spondylolisthesis with stenosis. LEVEL OF EVIDENCE: 2. PMID- 26839993 TI - Survivin-TGFB3-TIMP1 Gene Therapy Via Lentivirus Vector Slows the Course of Intervertebral Disc Degeneration in an In Vivo Rabbit Model. AB - STUDY DESIGN: The ability of lentivirus vector (LV) survivin-transforming growth factor beta 3 (TGFB3)-tissue inhibitor of metalloproteinases 1 (TIMP1) on slowing disc degeneration was evaluated by an animal experiment. OBJECTIVE: The aim of the study was to investigate the effect of LV survivin-TGFB3-TIMP1 on slowing disc degeneration in an in vivo rabbit model. SUMMARY OF BACKGROUND DATA: Cell apoptosis, increase of catabolic activity, and decrease of anabolic activity were the mechanisms of disc degeneration. Meanwhile, survivin, TGFB3, and TIMP1 can influence above process, respectively. However, there were no researches conducted to evaluate the effect of an LV containing all three proteins (referred to as LV-survivin-TGFB3-TIMP1) on slowing disc degeneration in vivo. METHODS: Twenty skeletally mature female New Zealand White rabbits were randomly divided into four groups: nonpunctured sham surgical group (group A, n = 5), punctured blank control group (group B, n = 5), punctured empty vector control group (group C, n = 5), and the treatment group (group D, n = 5). Computed tomography-guided puncture was performed at the L3-L4 and L4-L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, LV-carrying survivin, TGFB3, and TIMP1 were injected into the nucleus pulposus. Serial magnetic resonance imaging studies at 0, 3, and 12 weeks were performed. The rabbits were sacrificed at 12 weeks, and the histology, immunofluorescence, quantitative real-time polymerase chain reaction, Western blot, and caspase-3 activity was used for evaluation. RESULTS: Magnetic resonance imaging, histology, gene expression, protein content, and apoptosis analyses of group A showed no disc degeneration. Groups B and C showed disc degeneration, which increased over time, and no significant difference was observed between the two groups (P > 0.05). In group D, there was less disc degeneration compared to the punctured control groups and the difference was statistically significant (P < 0.05). CONCLUSION: The injection of LV-carrying survivin-TGFB3-TIMP1 into punctured rabbit intervertebral discs helps delay degenerative disc changes. Although data from animal models should be extrapolated to the human condition with caution, this study shows promise for gene therapy to decelerate disc degeneration. LEVEL OF EVIDENCE: N/A. PMID- 26839995 TI - Medialized, Muscle-Splitting Approach for Posterior Lumbar Interbody Fusion: Technique and Multicenter Perioperative Results. AB - STUDY DESIGN: Retrospective, multicenter study of perioperative results OBJECTIVE.: The purpose of this study was to describe the surgical technique for medialized posterior lumbar fusion as well as present preliminary complication and treatment results from a multicenter retrospective study. SUMMARY OF BACKGROUND DATA: Posterior exposures remain the most commonly performed approaches for spinal fusion. Conventional open posterior exposures, however, have relatively high exposure-related morbidity and postoperative infection rates. Less invasive exposures for transforaminal and anterior (lateral) interbody fusion have been widely used over the past decade, but the need for bilateral posterior exposure has challenged the development of less invasive exposures for direct posterior approaches for lumbar fusion. METHODS: Consecutive patients treated with minimally invasive spine (MIS) posterior lumbar interbody fusion with medialized cortical bone trajectory pedicle screw and rod fixation were identified from four sites in the United States. Of the 138 patients identified, 61% of patients were treated for degenerative spondylolisthesis at 167 levels, most commonly at L4-5 (62%). Perioperative treatment, complication, and reoperation data were collected to describe early feasibility of the approach. RESULTS: Mean total operative time was 135 minutes with an average of 236 mL of blood loss. Mean total postoperative length of hospital stay was 2.6 days, with 25% of patients discharged on the same day or within 23 hours of surgery. Total perioperative complication rate in 138 patients was 10.1% (14/138) with three related reoperations. Intraoperative complications included five (3.6%) instances of incidental durotomy, without any progression to persistent cerebrospinal fluid leaks. Nine (6.5%) postoperative complications occurred, including one L5 vertebral body fracture, two pulmonary embolisms, one deep vein thrombosis, one urinary tract infection one instance of urinary retention, two superficial surgical site infections, and one patient with persistent pain at 6 months postoperative. Three (2.2%) reoperations were performed, one for revision of the L5 vertebral body fracture, and two for wound debridement. No instances of postoperative radiculitis or neurological injury were observed. CONCLUSION: Medialized, muscle-sparing posterior exposures with specialized instrumentation can be performed in patients with degenerative lumbar pathology with low surgical morbidity and blood loss and a short length of postoperative hospital stay. LEVEL OF EVIDENCE: 4. PMID- 26839994 TI - Anterior Column Realignment (ACR) in Adult Sagittal Deformity Correction: Technique and Review of the Literature. AB - STUDY DESIGN: The anterior column realignment (ACR) procedure was retrospectively reviewed. OBJECTIVE: To review surgical technique, complication avoidance, case examples, and published results on ACR. SUMMARY OF BACKGROUND DATA: For surgical correction of sagittal imbalance, three column osteotomies (3CO) have traditionally been employed for large degrees of correction at a single segment. However, 3CO procedures are technically challenging and carry high morbidity rates. ACR was developed as a less invasive procedure for restoring segmental lordosis. METHODS: The ACR surgical technique is reviewed. ACR involves either a lateral, trans-psoas or anterior retroperitoneal approach to sectioning the anterior longitudinal ligament/annulus and placing a hyperlordotic cage. ACR usually also involves a second stage posterior column osteotomy. Three case examples are presented. A review of literature on ACR papers was completed. RESULTS: Twelve papers met inclusion criteria. Ten to 27 degrees of segmental lordosis were reported with use of hyperlordotic cages. 19 degrees increase in mean intradiscal angle was reported when ACR was combined with posterior column osteotomy, 13 degrees more than lateral lumbar interbody fusion alone without a hyperlordotic implant. Reported complication rates ranged from 18 to 47%. The most common minor complications were transient hip flexion weakness (9.3%) and transient paresthesia or dysesthesia (12%). There were few reports of major complications, such as bowel perforation (n = 1) or vascular injury (n = 1). Motor deficit was reported in 11 of 75 cases, lower than reported rates for 3CO. CONCLUSION: ACR is an emerging, less invasive technique for correction of sagittal deformity ACR has similar restorative capacity as other techniques with same or lower complication rates. LEVEL OF EVIDENCE: 4. PMID- 26839996 TI - Biomechanical Evaluation of the CD HORIZON Spire Z Spinal System With Pedicle and Facet Fixation. AB - STUDY DESIGN: Human cadaveric biomechanical study. OBJECTIVE: The aim of this study was to evaluate the biomechanics of lumbar motion segments instrumented with the CD HORIZON Spire Z plate system (Spire Z), a posterior supplemental fixation spinous process plate, alone and with additional fixation systems. SUMMARY OF BACKGROUND DATA: Plates and pedicle screw/rod and facet screw implants are adjuncts to fusion. The plate limits motion, improving segmental stability and the fusion microenvironment. However, the degree to which the plate contributes to overall stability when used alone or in conjunction with additional instrumentation has not been described. METHODS: Standard nondestructive flexibility tests were performed in 7 L2-L5 human cadaveric spines. Spinal stability was determined as mean range of motion (ROM) in flexion/extension, lateral bending, and axial rotation. Paired comparisons were made between five conditions: (1) intact/control; (2) Spire Z; (3) Spire Z with unilateral pedicle screw/rod system (Spire Z+UPS); (4) Spire Z with unilateral facet screw system (Spire Z+UFS); and (5) Spire Z with bilateral facet screw system (Spire Z+BFS). Stiffness and ROM data were compared using one-way analysis of variance, followed by repeated-measures Holm-Sidak tests. RESULTS: Spire Z was most effective in limiting flexion (20% of normal) and extension (24% of normal), but less effective in reducing lateral bending and axial rotation. In lateral bending, Spire Z+BFS and Spire Z+UPS constructs were not significantly different and demonstrated greater ROM reduction compared with Spire Z+UFS and Spire Z (P < 0.001). Spire Z+BFS demonstrated greatest stiffness in axial rotation compared with Spire Z+UPS (P = 0.025), Spire Z+UFS (P = 0.001), and Spire Z (P < 0.001). Spire Z+UPS was not significantly different from Spire Z+UFS (P = 0.21), and superior to Spire Z (P = 0.013). CONCLUSION: The Spire Z spinous process plate provides excellent immediate fixation, particularly for flexion and extension. While the hybrid Spire Z+BFS screw construct afforded the greatest stability, Spire Z+UPS demonstrated considerable promise. LEVEL OF EVIDENCE: N/A. PMID- 26839997 TI - Pharmacological perspectives from Brazilian Salvia officinalis (Lamiaceae): antioxidant, and antitumor in mammalian cells. AB - Salvia officinalis (Lamiaceae) has been used in south of Brazil as a diary homemade, in food condiment and tea-beverage used for the treatment of several disorders. The objective of this study was to characterize chemical compounds in the hydroalcoholic (ExtHS) and aqueous (ExtAS) extract from Salvia officinalis (L.) by gas chromatography-mass spectrometry (GC-MS) and by high-resolution electrospray ionization mass spectrometry (ESI-QTOF MS/MS), evaluate in vitro ability to scavenge the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH*) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS*+), catalase (CAT like) and superoxide dismutase (SOD-like) activity, moreover cytotoxic by MTT assay, alterations on cell morphology by giemsa and apoptotic-induced mechanism for annexin V/propidium iodide. Chemical identification sage extracts revealed the presence of acids and phenolic compounds. In vitro antioxidant analysis for both extracts indicated promising activities. The cytotoxic assays using tumor (Hep-2, HeLa, A-549, HT-29 and A-375) and in non-tumor (HEK-293 and MRC-5), showed selectivity for tumor cell lines. Immunocytochemistry presenting a majority of tumor cells at late stages of the apoptotic process and necrosis. Given the results presented here, Brazilian Salvia officinalis (L.) used as condiment and tea, may protect the body against some disease, in particularly those where oxidative stress is involved, like neurodegenerative disorders, inflammation and cancer. PMID- 26839998 TI - A new Mammutidae (Proboscidea, Mammalia) from the Late Miocene of Gansu Province, China. AB - The "Yanghecun specimen", a proboscidean specimen represented by a mandible from Miocene of China and previously described as Gomphotheriidae, is here reviewed and described as a new genus and species of Mammutidae: Sinomammut tobieni. This taxon is a longirostrine mastodon, lacking lower tusks, and bearing a wide last molar with oblique and non-inflated lophids, broad transverse interlophids, and yoke-like wear figures. Phylogenetic analysis of Mammutidae based on dental and mandibular features recovered S. tobieni as sister group of the mastodon Mammut. The longirostrine condition and the well-developed lower incisors seem to be primitive for Mammutidae, while the brevirostry is the derived condition, probably emerged during the middle Miocene (12-11 Mya). However, two derived conditions are recognized to the lower tusks: the absence of lower tusks (S. tobieni) and the occasional presence of vestigial lower tusks (Mammut). PMID- 26839999 TI - Investigation of potential biomarkers for the early diagnosis of cellular stability after the exposure of agricultural workers to pesticides. AB - Agricultural workers involved in the harvest of tobacco crops are regularly exposed to large quantities of pesticides. In order to determine how this exposure to pesticides induces genetic alterations in these workers, blood samples were obtained from 77 exposed individuals, as well as from 60 unexposed subjects. DNA damage was analyzed by the Comet assay and by the micronucleus (MN) test. The antioxidant profile was evaluated by activity of superoxide dismutase (SOD), and the polymorphism of gene PON1 was used as a susceptibility biomarker. The content of inorganic elements in the blood samples was determined by PIXE analysis. Our results demonstrated that the damage frequency, damage index, the MN frequency, and the SOD activity were significantly elevated in the exposed relative to the unexposed group. A modulation of the MN results for the PON1 gene was observed in the exposed group. The concentrations of inorganic elements in the exposed group were higher compared to those of the unexposed group. In this study, we observed that genetic damage, and change in oxidative balance were induced by the exposure of workers to complex mixtures of pesticides in the presence of inorganic compounds, whereby an influence of the genotype was evident. PMID- 26840000 TI - Geologic conceptual model of the municipality of Sete Lagoas (MG, Brazil) and the surroundings. AB - The study area is located in the state of Minas Gerais, Brazil, among the municipalities of Pedro Leopoldo, Matozinhos, and Sete Lagoas, with Velhas River as the eastern boundary. It is located in the Sao Francisco Craton, where carbonated argillo-arenaceous sediments are emplaced giving origin to the Bambui Group, in the Sao Francisco Basin. Despite the geological knowledge previously developed, the region needs work on integration and detailing of such information. For this reason, the main objective was to contribute to the quality of the geologic cartography, the spatial distribution, and the structural framework geometry. Thus, geologic mapping, aerial photography interpretation, and evaluation of 270 lithologic well profiles were carried out. It was possible to establish a new geologic perspective of the region by obtaining the detailed geologic map of the municipality of Sete Lagoas, 14 geologic cross sections, and a geologic conceptual model. The study showed that the area is within a basin border, presenting a geometry conditioned by horst and graben system controlled by faulting. This structural feature displaced stratigraphic sequences positioning them side by side with lithologic sequences with different ages. PMID- 26840001 TI - Influence of mass transfer on bubble plume hydrodynamics. AB - This paper presents an integral model to evaluate the impact of gas transfer on the hydrodynamics of bubble plumes. The model is based on the Gaussian type self similarity and functional relationships for the entrainment coefficient and factor of momentum amplification due to turbulence. The impact of mass transfer on bubble plume hydrodynamics is investigated considering different bubble sizes, gas flow rates and water depths. The results revealed a relevant impact when fine bubbles are considered, even for moderate water depths. Additionally, model simulations indicate that for weak bubble plumes (i.e., with relatively low flow rates and large depths and slip velocities), both dissolution and turbulence can affect plume hydrodynamics, which demonstrates the importance of taking the momentum amplification factor relationship into account. For deeper water conditions, simulations of bubble dissolution/decompression using the present model and classical models available in the literature resulted in a very good agreement for both aeration and oxygenation processes. Sensitivity analysis showed that the water depth, followed by the bubble size and the flow rate are the most important parameters that affect plume hydrodynamics. Lastly, dimensionless correlations are proposed to assess the impact of mass transfer on plume hydrodynamics, including both the aeration and oxygenation modes. PMID- 26840002 TI - Feeding ecology of Erythrolamprus jaegeri jaegeri (Gunter, 1858) and Erythrolamprus poecilogyrus sublineatus (Cope, 1860) in the coastal zone of Subtropical Brazil (Serpentes, Dipsadidae). AB - The snakes Erythrolamprus jaegeri jaegeri and Erythrolamprus poecilogyrus sublineatus are sympatric and syntopic in the coastal region of southern Brazil. Herein, we analyzed the diet composition to evaluate the niche breadth and the prey selection by both species. We examined 192 specimens, and analysis of stomach contents revealed that both species predominantly consume anurans. However, the diet of E. j. jaegeri consists mainly of fish and amphibians, whereas that of E. p. sublineatus is broader, including fish, amphibians, reptiles and mammals. The Standardized Levins Index presented lower values for E. j. jaegeri (BA = 0.17) than for E. p. sublineatus (BA = 0.61), evidencing specialist and generalist strategies for each species, respectively. Regarding prey selection, E. p. sublineatus presented a larger snout-vent length, head, mouth and lower jaw than E. j. jaegeri and fed on larger prey. In addition, positive correlations between the size and weight of predators and prey were confirmed in both species. The results show the development of different mechanisms for co-occurrence of the two species, such as prey selection by size, such that the size of the predator is related to the size of their prey, or by developing different strategies to decrease niche overlap between species. PMID- 26840003 TI - Plankton community dynamics in a subtropical lagoonal system and related factors. AB - Changes of the plankton community in a shallow, subtropical lagoonal system and its relation to environmental conditions were investigated during an annual cycle to provide information on its spatial and seasonal variation pattern. The study carried out at four sites (three in the Peixe lagoon and one in the Ruivo lagoon), which are located in the Lagoa do Peixe National Park, southern Brazil. The system has a temporary connection to the Atlantic Ocean by a narrow channel. The phytoplankton density was higher in the Peixe lagoon whereas the specific richness was higher in the Ruivo lagoon which is also a site with the lower salinity. The phytoplankton biomass near the channel showed seasonal variation with the highest value in fall and lowest in winter. Zooplankton richness was inversely correlated with salinity, and had the highest values in the Ruivo lagoon. Ordination analysis indicated seasonal and spatial patterns in plankton community in this lagoonal system, related to variation in salinity. In addition, the wind action and precipitation were important factors on the spatial and seasonal salinity changes in the lagoon with direct influence on the plankton community dynamics. PMID- 26840004 TI - Evaluation of genotoxic and cytotoxic effects of hydroalcoholic extract of Euphorbia tirucalli (Euphorbiaceae) in cell cultures of human leukocytes. AB - Euphorbia tirucalli (L.), commonly known as aveloz, has been indiscriminately used in popular medicine to treat various illnesses. However, some components can have devastating consequences. Injury to a cell's genetic material can cause mutations, cancer, and cell death. Our main goal in this work was to evaluate the genotoxic and cytotoxic effects of E. tirucalli extract on human leukocytes. For this purpose, we performed a phytochemical analysis to evaluate the plant's components. In the second step, we treated cultured human leukocytes with different concentrations of the dry extract of the plant and then evaluated the oxidative and genotoxic profiles of these leukocytes. We found that at 1% and 10% concentrations, the aveloz extract acted as a genotoxic agent that could damage DNA and increase oxidative damage. We conclude that despite its popular use, aveloz can act as a genotoxic agent, especially when it contains phorbol ester. Aveloz's indiscriminate use might actually promote tumors and therefore carry a considerable genetic risk for its users. PMID- 26840005 TI - Antinociceptive and anti-inflammatory effects of a Geissospermum vellosii stem bark fraction. AB - Geissospermum vellosii (Pao pereira) is a Brazilian tree whose stem barks are rich in indole alkaloids that present intense anticholinesterase activity. The present study evaluated the effects of a stem bark fraction (PPAC fraction) and ethanolic extract (EE) of Pao pereira in classic murine models of inflammation and pain. The EE and PPAC fraction, both at a dose of 30 mg/kg, significantly reduced mice abdominal constriction induced by acetic acid by 34.8% and 47.5%, respectively. In the formalin test, EE (30 mg/kg) and PPAC fraction (30 and 60 mg/kg) inhibited only the second phase, by 82.8%, 84.9% and 100%, respectively. Compared with indomethacin, similar doses of EE or PPAC fraction were approximately twice as effective in causing antinociception. PPAC fraction was not effective in the hot plate test but reduced the inflammatory response at the second (50.6%) and third (57.8%) hours of rat paw edema induced by carrageenan. Antihyperalgesic activity was observed within 30 min with a peak at 2 h (60.1%). These results demonstrate that compounds in PPAC fraction have anti-inflammatory and antinociceptive activity by a mechanism apparently unrelated to the opioid system. Regardless of similar responses to indomethacin, the effects of PPAC fraction are mainly attributed to acetylcholine actions. PMID- 26840006 TI - Integrated evaluation of the geology, aerogammaspectrometry and aeromagnetometry of the Sul-Riograndense Shield, southernmost Brazil. AB - An integrated evaluation of geology, aerogammaspectrometry and aeromagnetometry of the Sul-Riogran-dense Shield is permitted by the advanced stage of understanding of the geology and geochronology of the southern Brazilian Shield and a 2010 airborne geophysical survey. Gamma rays are registered from the rocks near the surface and thus describe the distribution of major units in the shield, such as the Pelotas batholith, the juvenile Sao Gabriel terrane, the granulite amphibolite facies Taquarembo terrane and the numerous granite intrusions in the foreland. Major structures are also observed, e.g., the Dorsal de Cangucu shear. Magnetic signals register near surface crustal compositions (analytic signal) and total crust composition (total magnetic signal), so their variation as measured indicates either shallow or whole crustal structures. The Cacapava shear is outstanding on the images as is the magnetic low along the N-S central portion of the shield. These integrated observations lead to the deepening of the understanding of the largest and even detailed structures of the Sul-Riograndense Shield, some to be correlated to field geology in future studies. Most significant is the presence of different provinces and their limits depending on the method used for data acquisition - geology, aerogammaspectrometry or aeromagnetometry. PMID- 26840007 TI - Respiratory diphtheria in an asylum seeker from Afghanistan arriving to Finland via Sweden, December 2015. AB - In December 2015, an asylum seeker originating from Afghanistan was diagnosed with respiratory diphtheria in Finland. He arrived in Finland from Sweden where he had already been clinically suspected and tested for diphtheria. Corynebacterium diphtheriae was confirmed in Sweden and shown to be genotypically and phenotypically toxigenic. The event highlights the importance of early case detection, rapid communication within the country and internationally as well as preparedness plans of diphtheria antitoxin availability. PMID- 26840008 TI - Pediatric bronchiectasis: No longer an orphan disease. AB - Bronchiectasis is described classically as a chronic pulmonary disorder characterized by a persistent productive cough and irreversible dilatation of one or more bronchi. However, in children unable to expectorate, cough may instead be wet and intermittent and bronchial dilatation reversible in the early stages. Although still considered an orphan disease, it is being recognized increasingly as causing significant morbidity and mortality in children and adults in both affluent and developing countries. While bronchiectasis has multiple etiologies, the final common pathway involves a complex interplay between the host, respiratory pathogens and environmental factors. These interactions lead to a vicious cycle of repeated infections, airway inflammation and tissue remodelling resulting in impaired airway clearance, destruction of structural elements within the bronchial wall causing them to become dilated and small airway obstruction. In this review, the current knowledge of the epidemiology, pathobiology, clinical features, and management of bronchiectasis in children are summarized. Recent evidence has emerged to improve our understanding of this heterogeneous disease including the role of viruses, and how antibiotics, novel drugs, antiviral agents, and vaccines might be used. Importantly, the management is no longer dependent upon extrapolating from the cystic fibrosis experience. Nevertheless, substantial information gaps remain in determining the underlying disease mechanisms that initiate and sustain the pathophysiological pathways leading to bronchiectasis. National and international collaborations, standardizing definitions of clinical and research end points, and exploring novel primary prevention strategies are needed if further progress is to be made in understanding, treating and even preventing this often life-limiting disease. PMID- 26840010 TI - Psychometric Properties of the Slovak and Czech Versions of the Evidence-Based Practice Beliefs and Implementation Scales. AB - BACKGROUND: The Evidence-Based Practice Beliefs (EBP-B) and Evidence-Based Practice Implementation (EBP-I) scales are psychometrically sound instruments that were used, within an educational setting, to systematically study students' beliefs about and their implementation of evidence-based practice (EBP). Czech and Slovak versions of these instruments were developed and evaluated using a sample population of nursing students. PURPOSE: The purpose of the study was to test the psychometric properties of the Czech and Slovak versions of the EBP-B and EBP-I scales. METHODS: Psychometric properties were evaluated using a sample of undergraduate and graduate (nearly graduated) nursing students (n = 223) completing EBP courses. To test psychometric properties of the questionnaire, its reliability and validity were explored. Cronbach's alpha was computed to evaluate internal structure and internal consistency. RESULTS: The Slovak versions of both the EBP-B and the EBP-I scale have good internal consistency (Cronbach's alpha: .82 and .94, respectively). Similarly, the Czech versions of the EBP-B and the EBP-I scales both have good internal consistency (Cronbach's alpha: .85 and .89, respectively). LINKING EVIDENCE TO ACTION: The results of psychometric analysis of the Czech and Slovak versions of the EBP-B and the EBP-I scales are consistent with the results of the original study and indicate that the Czech and Slovak versions have the potential to be valid, reliable, and sensitive instruments for measuring an individual's beliefs about the value of EBP and their ability to implement it. Both instruments can be used to assess changes in nurses' beliefs about EBP over time as well as the effectiveness of strategies aimed at promoting the use of evidence in practice. PMID- 26840011 TI - Peptide bond-forming reagents HOAt and HATU are not mutagenic in the bacterial reverse mutation test. AB - The peptide bond-forming reagents 1-hydroxy-7-azabenzotriazole (HOAt, CAS 39968 33-7) and O-(7-Azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU, CAS 148893-10-1) either have structural alerts, unclassified features or are considered out of domain when evaluated for potential mutagenicity with in silico programs DEREK and CaseUltra. Since they are commonly used reagents in pharmaceutical drug syntheses, they may become drug substance or drug product impurities and would need to be either controlled to appropriately safe levels or tested for mutagenicity. Both reagents were tested in the bacterial reverse mutation (Ames) test at Covance, under GLP conditions, following the OECD test guideline and ICH S2(R1) recommendations and found to be negative. Our data show that HOAt and HATU-common pharmaceutical synthesis reagents-are not mutagenic, and can be treated as ordinary drug impurities. PMID- 26840012 TI - The use of asymmetric distributions in average bioequivalence. AB - Generic drugs have been commercialized in numerous countries. Most of these countries approve the commercialization of a generic drug when there is evidence of bioequivalence between the generic drug and the reference drug. Generally, the pharmaceutical industry is responsible for the bioequivalence test under the supervision of a regulatory agency. This procedure is concluded after a statistical data analysis. Several agencies adopt a standard statistical analysis based on procedures that were previously established. In practice, we face situations in which this standard model does not fit to some sets of bioequivalence data. In this study, we propose an evaluation of bioequivalence using univariate and bivariate models based on an extended generalized gamma distribution and a skew-t distribution, under a Bayesian perspective. We introduce a study of the empirical power of hypothesis tests for univariate models, showing advantages in the use of an extended generalized gamma distribution. Three sets of bioequivalence data were analyzed under these new procedures and compared with the standard model proposed by the majority of regulatory agencies. In order to verify that the asymmetrical distributions are usually better fitted for the data, when compared with the standard model, model discrimination methods were used, such as the Deviance Information Criterion (DIC) and quantile-quantile plots. The research concluded that, in general, the use of the extended generalized gamma distribution may be more appropriate to model bioequivalence data in the original scale. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26840009 TI - Concise Review: Cell-Based Therapies and Other Non-Traditional Approaches for Type 1 Diabetes. AB - The evolution of Type 1 diabetes (T1D) therapy has been marked by consecutive shifts, from insulin replacement to immunosuppressive drugs and targeted biologics (following the understanding that T1D is an autoimmune disease), and to more disease-specific or patient-oriented approaches such as antigen-specific and cell-based therapies, with a goal to provide efficacy, safety, and long-term protection. At the same time, another important paradigm shift from treatment of new onset T1D patients to prevention in high-risk individuals has taken place, based on the hypothesis that therapeutic approaches deemed sufficiently safe may show better efficacy if applied early enough to maintain endogenous beta cell function, a concept supported by many preclinical studies. This new strategy has been made possible by capitalizing on a variety of biomarkers that can more reliably estimate the risk and rate of progression of the disease. More advanced ("omic"-based) biomarkers that also shed light on the underlying contributors of disease for each individual will be helpful to guide the choice of the most appropriate therapies, or combinations thereof. In this review, we present current efforts to stratify patients according to biomarkers and current alternatives to conventional drug-based therapies for T1D, with a special emphasis on cell-based therapies, their status in the clinic and potential for treatment and/or prevention. PMID- 26840013 TI - Photoinduced Electron Transfer Elicits a Change in the Static Dielectric Constant of a de Novo Designed Protein. AB - We provide a direct measure of the change in effective dielectric constant (epsilon(S)) within a protein matrix after a photoinduced electron transfer (ET) reaction. A linked donor-bridge-acceptor molecule, PZn-Ph-NDI, consisting of a (porphinato)Zn donor (PZn), a phenyl bridge (Ph), and a naphthalene diimide acceptor (NDI), is shown to be a "meter" to indicate protein dielectric environment. We calibrated PZn-Ph-NDI ET dynamics as a function of solvent dielectric, and computationally de novo designed a protein SCPZnI3 to bind PZn-Ph NDI in its interior. Mapping the protein ET dynamics onto the calibrated ET catalogue shows that SCPZnI3 undergoes a switch in the effective dielectric constant following photoinduced ET, from epsilon(S) ~ 8 to epsilon(S) ~ 3. PMID- 26840014 TI - The influence of status and the social environment on energy stores in a social fish. AB - This study explores how muscle and liver energy stores are linked with social status and the social environment in Neolamprologus pulcher, a cooperatively breeding fish that lives in colonies comprised of up to 200 distinct social groups. Subordinate muscle energy stores were positively correlated with the number of neighbouring social groups in the colony, but this pattern was not observed in dominant N. pulcher. Furthermore, liver energy stores were smaller in dominants living at the edge of the colony compared with those living in the colony centre, with no differences among subordinates in liver energy stores. Subordinate N. pulcher may build up large energy stores in the muscles to fuel rapid growth after dispersal, which could occur more frequently in high-density environments. Dominant N. pulcher may use the more easily mobilized energy stores in the liver to fuel daily activities, which could be more energetically demanding on the edge of the colony as a result of the increased predation defence needed on the edge. Overall, this study demonstrates that both subordinate and dominant physiology in N. pulcher varies with characteristics of the social environment. Furthermore, dominant and subordinate energy storage strategies appear to differ due to status-dependent variation in daily activities and variation in the need to prepare for future reproductive or dispersal opportunities. PMID- 26840015 TI - Enantiomeric resolution of multiple chiral centres racemates by capillary electrophoresis. AB - Enantiomeric resolution of multichiral centre racemates is an important area as some multichiral centre racemates are of great medicinal importance. However, enantioseparation of such types of racemates is a challenging task. Amongst many analytical techniques, capillary electrophoresis is a powerful technique and may be used to resolve such racemates. Only few papers are available describing enantiomeric resolution of such racemates. Therefore, efforts have been made to describe the enantiomeric resolution of multichiral centre racemates by capillary electrophoresis. This article discusses the importance of multichiral racemates, the need for capillary electrophoresis in enantiomeric resolution and chiral resolution of multichiral centre racemates using various chiral selectors. Further, attempts have been made to discuss the future challenges and prospects of enantiomeric resolution of multichiral racemates. The various chiral selectors used for the purpose are chiral crown ether, cyclodextrins, polysaccharides, macrocyclic glycopeptide antibiotics and ligand exchange. PMID- 26840016 TI - Supply and Demand Analysis of the Orthopaedic Trauma Surgeon Workforce in the United States. AB - OBJECTIVE: To investigate recent trends in the orthopaedic trauma workforce and to assess whether supply of orthopaedic trauma surgeons (OTS) matches the demand for their skills. METHODS: Supply estimated using Orthopaedic Trauma Association (OTA) membership and American Academy of Orthopaedic Surgeons census data. The annual number of operative pelvic and acetabular fractures reported by American College of Surgeons verified trauma centers in the National Trauma Data Bank (NTDB) was used as a surrogate of demand. Because surrogates were used, the annual rate of change in OTA membership versus rate of change in operative injuries per NTDB center was compared. RESULTS: From 2002 to 2012, reported operative pelvic and acetabular injuries increased by an average of 21.0% per year. The number of reporting trauma centers increased by 27.2% per year. The number of OTA members increased each year except in 2009, with mean annual increase of 9.8%. The mean number of orthopaedic surgeons per NTDB center increased from 7.98 to 8.58, an average of 1.5% per year. The annual number of operative pelvic and acetabular fractures per NTDB center decreased from 27.1 in 2002 to 19.03 in 2012, down 2.0% per year. CONCLUSIONS: In the United States, from 2002 to 2012, the number of OTS trended upward, whereas operative pelvic and acetabular cases per reporting NTDB center declined. These trends suggest a net loss of such cases per OTS over this period. PMID- 26840017 TI - High level of BRD4 promotes non-small cell lung cancer progression. AB - Bromodomain containing protein 4 (BRD4), a member of the bromodomain and extra terminal domain (BET) protein family, has been shown to play important roles in tumor progression. However, its role in non-small cell lung cancer (NSCLC) is still largely unknown. Here, we found that BRD4 expression was significantly upregulated in NSCLC tissues and NSCLC cell lines with higher invasion and metastasis potentials. Suppression of BRD4 expression in NSCLC cell lines impaired cell invasion, inhibited cell proliferation, and accelerated cell apoptosis. Clinically, we observed that the BRD4 level was significantly related to histological type, lymph node metastasis, tumor stage and differentiation. More importantly, high level of BRD4 was closely correlated with the poor prognosis of NSCLC patients. Therefore, our study suggests that BRD4 is one of the major contributors to the invasion-prone phenotype of NSCLC, and a potential therapeutic target of NSCLC. PMID- 26840018 TI - Hsa-miR-326 targets CCND1 and inhibits non-small cell lung cancer development. AB - Hsa-miRNA-326 (miR-326) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-326 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-326 on the development of NSCLC. The results indicated that miR-326 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-326 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-326 induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-326 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene CCND1 was revealed to be a putative target of miR-326, which was inversely correlated with miR-326 expression in NSCLC. Taken together, our results demonstrated that miR-326 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1. PMID- 26840019 TI - Toward targeted therapy in chemotherapy-resistant pancreatic cancer with a smart triptolide nanomedicine. AB - Chemoresistance is the major impediment for treating pancreatic cancer. Herb derived compound triptolide (TP) can inhibit proliferation of chemo-resistant pancreatic cancer (CPC) cell lines through multiple mechanisms, which exhibited superior anticancer efficacy compared with gemcitabine. However, toxicity due to non-specific exposure to healthy tissues hindered its clinical translation. Herein we successfully achieved targeting CPC cells and avoiding exposure to healthy tissues for TP by nucleolin-specific aptamer (AS1411) mediated polymeric nanocarrier. We conjugated AS1411 aptamer to carboxy terminated poly(ethylene glycol)-block-poly(d, l-lactide) (HOOC-PEG-PDLLA), then prepared AS1411-PEG-PDLLA micelle loading TP (AS-PPT) through solid dispersion technique. AS-PPT showed more antitumor activity than TP and equivalent specific binding ability with gemcitabine-resistant human pancreatic cancer cell (MIA PaCa-2) to AS1411 aptamer in vitro. Furthermore, we studied the distribution of AS-PPT (Cy3-labed TP) at tissue and cellular levels using biophotonic imaging technology. The results showed AS1411 facilitated TP selectively accumulating in tumor tissues and targeting CPC cells. The lifetime of the MIA PaCa-2 cell-bearing mice administrated with AS-PPT was efficiently prolonged than that of the mice subjected to the clinical anticancer drug Gemzar(r) in vivo. Such work provides a new strategy for overcoming the drug resistance of pancreatic cancer. PMID- 26840020 TI - Polycomb complex protein BMI-1 promotes invasion and metastasis of pancreatic cancer stem cells by activating PI3K/AKT signaling, an ex vivo, in vitro, and in vivo study. AB - Cancer stem cell theory indicates cancer stem cells are the key to promote tumor invasion and metastasis. Studies showed that BMI-1 could promote self-renew, differentiation and tumor formation of CSCs and invasion/metastasis of human cancer. However, whether BMI-1 could regulate invasion and metastasis ability of CSCs is still unclear. In our study, we found that up-regulated expression of BMI 1 was associated with tumor invasion, metastasis and poor survival of pancreatic cancer patients. CD133+ cells were obtained by using magnetic cell sorting and identified of CSCs properties such as self-renew, multi-differentiation and tumor formation ability. Then, we found that BMI-1 expression was up-regulated in pancreatic cancer stem cells. Knockdown of BMI-1 expression attenuated invasion ability of pancreatic cancer stem cells in Transwell system and liver metastasis capacity in nude mice which were injected CSCs through the caudal vein. We are the first to reveal that BMI-1 could promote invasion and metastasis ability of pancreatic cancer stem cells. Finally, we identified that BMI-1 expression activating PI3K/AKT singing pathway by negative regulating PTEN was the main mechanism of promoting invasion and metastasis ability of pancreatic CSCs. In summary, our findings indicate that BMI-1 could be used as the therapeutic target to inhibiting CSCs-mediated pancreatic cancer metastasis. PMID- 26840021 TI - Construction of a new anti-CD19 chimeric antigen receptor and the anti-leukemia function study of the transduced T cells. AB - Chimeric antigen receptor (CAR) transduced T cells have been used to efficiently kill the target tumor cells depending on the single chain variable fragment (scFv) against the specific tumor associated antigen. Here we show the high specific cytotoxicity of the CAR-T cells with very low effector to target cell (E:T) ratio owing to the CD19-scFv, which was constructed in our laboratory and proved to be highly effective in our previous study. Four plasmids containing three generation of CAR were constructed by cloning the CD19-CAR fragment into the lentiviral vector pCDH. CD3 positive T cells were successfully transduced and the CAR protein expression was confirmed by flow cytometry and Western blot. When cocultured with CD19 positive leukemia cell line Nalm-6 cells, CAR-T cells showed specific cytotoxicity: the percentage of target cells decreased to 0 in 24 hours; IL-2, IFN-gamma and TNF-alpha produced in cocultured supernatants increased obviously; and the cytotoxicity reached more than 80%, still remarkable even when the E:T ratio was as low as 1:4. Dynamic change of cell interaction between CAR-T and leukemia cells was visually tracked by using living cells workstation for the first time. A NOD/SCID B-ALL murine model was established using Nalm-6 cells inoculation with a morbidity rate of 100%, and the survival time was prolonged statistically with CAR-T cell treatment. These data demonstrate that the CAR-T cells we prepared could be a promising treatment strategy for CD19 positive tumor diseases. PMID- 26840022 TI - KRAS mutation is a weak, but valid predictor for poor prognosis and treatment outcomes in NSCLC: A meta-analysis of 41 studies. AB - Mutation of oncogene KRAS is common in non-small cell lung cancer (NSCLC), however, its clinical significance is still controversial. Independent studies evaluating its prognostic and predictive value usually drew inconsistent conclusions. Hence, We performed a meta-analysis with 41 relative publications, retrieved from multi-databases, to reconcile these controversial results and to give an overall impression of KRAS mutation in NSCLC. According to our findings, KRAS mutation was significantly associated with worse overall survival (OS) and disease-free survival (DFS) in early stage resected NSCLC (hazard ratio or HR=1.56 and 1.57, 95% CI 1.39-1.76 and 1.17-2.09 respectively), and with inferior outcomes of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR TKIs) treatment and chemotherapy (relative risk or RR=0.21 and 0.66 for objective response rate or ORR, 95% CI 0.12-0.39 and 0.54-0.81 respectively; HR=1.46 and 1.30 for progression-free survival or PFS, 95%CI 1.23-1.74 and 1.14-1.50 respectively) in advanced NSCLC. When EGFR mutant patients were excluded, KRAS mutation was still significantly associated with worse OS and PFS of EGFR-TKIs (HR=1.40 and 1.35, 95 % CI 1.21-1.61 and 1.11-1.64). Although KRAS mutant patients presented worse DFS and PFS of chemotherapy (HR=1.33 and 1.11, 95% CI 0.97-1.84 and 0.95-1.30), and lower response rate to EGFR-TKIs or chemotherapy (RR=0.55 and 0.88, 95 % CI 0.27-1.11 and 0.76-1.02), statistical differences were not met. In conclusion, KRAS mutation is a weak, but valid predictor for poor prognosis and treatment outcomes in NSCLC. There's a need for developing target therapies for KRAS mutant lung cancer and other tumors. PMID- 26840023 TI - Risk stratification based on change in plasma Epstein-Barr virus DNA load after treatment in nasopharyngeal carcinoma. AB - BACKGROUND: Nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV). The current study investigated change in the plasma EBV DNA load in the first 3 months after treatment and its clinical significance in NPC. METHODS: A total of 273 patients with non-metastatic, histologically-proven NPC treated with radiotherapy or chemoradiotherapy were retrospectively reviewed. RESULTS: EBV DNA was detectable in 19/273 (7.0%) patients at the end of therapy (end-DNA). Three months later, 16/273 (5.9%) patients had detectable EBV DNA (3-month-DNA). To investigate risk stratified by the pattern of change in post-treatment EBV-DNA, we divided patients into four subgroups: Group 1, undetectable end-DNA and 3 month-DNA (n = 244); Group 2, detectable end-DNA and undetectable 3-month-DNA (n = 13); Group 3, undetectable end-DNA and detectable 3-month-DNA (n = 7); and Group 4, detectable end-DNA and 3-month-DNA (n = 2). Patients with delayed remission of EBV DNA after treatment (Group 2) had significantly poorer 3-year DFS (48.6% vs. 89.7%, P < 0.001), DMFS (48.6% vs. 94.6%, P < 0.001) and OS (91.7% vs. 97.5%, P < 0.001) than those with persistently undetectable EBV DNA post treatment (Group 1). Five of the seven patients with re-emergent EBV DNA (Group 3) and both patients with persistent EBV DNA post-treatment (Group 4) developed disease failure. CONCLUSION: Plasma EBV DNA load continues to change during the first 3 months after treatment. The pattern of change in EBV DNA load post treatment could help identify patients with different prognoses. PMID- 26840024 TI - Role of CD44(high)/CD133(high) HCT-116 cells in the tumorigenesis of colon cancer. AB - This study aimed to explore cell surface biomarkers related to cancer stem cells (CSCs) and their role in the tumorigenesis of colon cancer. Various colon cancer cell lines were screened for CD133 and CD44 expression. CD44(high)/CD133(high) and CD44(low)/CD133(low) cells were separately isolated by Fluorescence-Activated Cell Sorting (FACS). The cell proliferation, colony formation, cell cycle characteristics, and tumorigenic properties in CD44(high)/CD133(high) and CD44(low)/CD133(low) cells were investigated through in vitro experiments and in vivo tumor xenograft models. The expression profiles of stem cell-related genes were examined by RT-PCR. With HCT-116 cells, flow cytometry analysis revealed that CD44(high)/CD133(high) cells had higher proliferation potency than CD44(low)/CD133(low) cells. Compared to CD44(low)/CD133(low) cells, CD44(high)/CD133(high) cells had more stem cell-related genes, and displayed increased tumorigenic ability. In summary, CD44(high)/CD133(high) cells isolated from HCT-116 cells harbor CSC properties that may be related to the tumor growth of colon cancer. These results suggest that CD44 and CD133 could be strong markers of colorectal cancer stem cells. PMID- 26840025 TI - Small molecule screen for inhibitors of expression from canonical CREB response element-containing promoters. AB - The transcription factor CREB (cAMP Response Element Binding Protein) is an important determinant in the growth of Acute Myeloid Leukemia (AML) cells. CREB overexpression increases AML cell growth by driving the expression of key regulators of apoptosis and the cell cycle. Conversely, CREB knockdown inhibits proliferation and survival of AML cells but not normal hematopoietic cells. Thus, CREB represents a promising drug target for the treatment of AML, which carries a poor prognosis. In this study, we performed a high-throughput small molecule screen to identify compounds that disrupt CREB function in AML cells. We screened ~114,000 candidate compounds from Stanford University's small molecule library, and identified 5 molecules that inhibit CREB function at micromolar concentrations, but are non-toxic to normal hematopoietic cells. This study suggests that targeting CREB function using small molecules could provide alternative approaches to treat AML. PMID- 26840026 TI - Identification of cancer chemopreventive isothiocyanates as direct inhibitors of the arylamine N-acetyltransferase-dependent acetylation and bioactivation of aromatic amine carcinogens. AB - Aromatic amines (AAs) are chemicals of industrial, pharmacological and environmental relevance. Certain AAs, such as 4-aminobiphenyl (4-ABP), are human carcinogens that require enzymatic metabolic activation to reactive chemicals to form genotoxic DNA adducts. Arylamine N-acetyltransferases (NAT) are xenobiotic metabolizing enzymes (XME) that play a major role in this carcinogenic bioactivation process. Isothiocyanates (ITCs), including benzyl-ITC (BITC) and phenethyl-ITC (PEITC), are phytochemicals known to have chemopreventive activity against several aromatic carcinogens. In particular, ITCs have been shown to modify the bioactivation and subsequent mutagenicity of carcinogenic AA chemicals such as 4-ABP. However, the molecular and biochemical mechanisms by which these phytochemicals may modulate AA carcinogens bioactivation and AA-DNA damage remains poorly understood. This manuscript provides evidence indicating that ITCs can decrease the metabolic activation of carcinogenic AAs via the irreversible inhibition of NAT enzymes and subsequent alteration of the acetylation of AAs. We demonstrate that BITC and PEITC react with NAT1 and inhibit readily its acetyltransferase activity (k(i) = 200 M(-1).s(-1) and 66 M(-1).s(-1) for BITC and PEITC, respectively). Chemical labeling, docking approaches and substrate protection assays indicated that inhibition of the acetylation of AAs by NAT1 was due to the chemical modification of the enzyme active site cysteine. Moreover, analyses of AAs acetylation and DNA adducts in cells showed that BITC was able to modulate the endogenous acetylation and bioactivation of 4-ABP. In conclusion, we show that direct inhibition of NAT enzymes may be an important mechanism by which ITCs exert their chemopreventive activity towards AA chemicals. PMID- 26840027 TI - An individualized prognostic signature for gastric cancer patients treated with 5 Fluorouracil-based chemotherapy and distinct multi-omics characteristics of prognostic groups. AB - 5-Fluorouracil (5-FU)-based chemotherapy is currently the first-line treatment for gastric cancer. In this study, using gene expression profiles for a panel of cell lines with drug sensitivity data and two cohorts of patients, we extracted a signature consisting of two gene pairs (KCNE2 and API5, KCNE2 and PRPF3) whose within-sample relative expression orderings (REOs) could robustly predict prognoses of gastric cancer patients treated with 5-FU-based chemotherapy. This REOs-based signature was insensitive to experimental batch effects and could be directly applied to samples measured by different laboratories. Taking this unique advantage of the REOs-based signature, we classified gastric cancer samples of The Cancer Genome Atlas (TCGA) into two prognostic groups with distinct transcriptional characteristics, circumventing the usage of confounded TCGA survival data. We further showed that the two prognostic groups displayed distinct copy number, gene mutation and DNA methylation landscapes using the TCGA multi-omics data. The results provided hints for understanding molecular mechanisms determining prognoses of gastric cancer patients treated with 5-FU based chemotherapy. PMID- 26840029 TI - Meditation for adults with haematological malignancies. AB - BACKGROUND: Malignant neoplasms of the lymphoid or myeloid cell lines including lymphoma, leukaemia and myeloma are referred to as haematological malignancies. Complementary and alternative treatment options such as meditation practice or yoga are becoming popular by treating all aspects of the disease including physical and psychological symptoms. However, there is still unclear evidence about meditation's effectiveness, and how its practice affects the lives of haematologically-diseased patients. OBJECTIVES: This review aims to assess the benefits and harms of meditation practice as an additional treatment to standard care for adults with haematological malignancies. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 8, 2015), MEDLINE (1950 to August 2015), databases of ongoing trials, the metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/), conference proceedings of annual meetings of: the American Society of Hematology; American Society of Clinical Oncology; European Hematology Association; European Congress for Integrative Medicine; and Global Advances in Health and Medicine (2010 to 2015). SELECTION CRITERIA: We included randomised controlled trials (RCTs) using meditation practice for adult patients with haematological malignancies. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from eligible studies and assessed the risk of bias according to predefined criteria. We evaluated quality of life and depression. The other outcomes of overall survival, anxiety, fatigue, quality of sleep and adverse events could not be evaluated, because they were not assessed in the included trial. MAIN RESULTS: We included only one small trial published as an abstract article. The included study investigated the effects of meditation practice on patients newly hospitalised with acute leukaemia. Ninety-one participants enrolled in the study, but only 42 participants remained in the trial throughout the six-month follow-up period and were eligible for analysis. There was no information provided about the average age and sex of the study population. We found a high risk for attrition bias and unclear risk for reporting bias, performance and detection bias because of missing data due to abstract publication only, thus we judged the overall risk of bias as high. According to the GRADE criteria, we judged the overall quality of the body of evidence for all predefined outcomes as 'very low', due to the extent of missing data on the study population, and the small sample size.As the abstract publication did not provide numbers and results except P values, we are not able to give more details.Meditation practice might be beneficial for the quality of life of haematologically-diseased patients, with higher scores for participants in the mediation arms compared to the participants in the usual care control group (low quality of evidence). Levels of depression decreased for those practising meditation in both the spiritually-framed meditation group and the secularly-focused meditation group in comparison to the usual care control group, whose levels of depression remained constant (low quality of evidence). The influence of meditation practice on overall survival, fatigue, anxiety, quality of sleep and adverse events remained unclear, as these outcomes were not evaluated in the included trial. AUTHORS' CONCLUSIONS: To estimate the effects of meditation practice for patients suffering from haematological malignancies, more high quality randomised controlled trials are needed. At present there is not enough information available on the effects of meditation in haematologically-diseased patients to draw any conclusion. PMID- 26840028 TI - microRNA-1827 represses MDM2 to positively regulate tumor suppressor p53 and suppress tumorigenesis. AB - The tumor suppressor p53 plays a central role in tumor prevention. The E3 ubiquitin ligase MDM2 is the most critical negative regulator of p53, which binds to p53 and degrades p53 through ubiquitation. MDM2 itself is a transcriptional target of p53, and therefore, MDM2 forms a negative feedback loop with p53 to tightly regulate p53 levels and function. microRNAs (miRNAs) play a key role in regulation of gene expression. miRNA dysregulation plays an important role in tumorigenesis. In this study, we found that miRNA miR-1827 is a novel miRNA that targets MDM2 through binding to the 3'-UTR of MDM2 mRNA. miR-1827 negatively regulates MDM2, which in turn increases p53 protein levels to increase transcriptional activity of p53 and enhance p53-mediated stress responses, including apoptosis and senescence. Overexpression of miR-1827 suppresses the growth of xenograft colorectal tumors, whereas the miR-1827 inhibitor promotes tumor growth in mice in a largely p53-dependent manner. miR-1827 is frequently down-regulated in human colorectal cancer. Decreased miR-1827 expression is associated with high MDM2 expression and poor prognosis in colorectal cancer. In summary, our results reveal that miR-1827 is a novel miRNA that regulates p53 through targeting MDM2, and highlight an important role and the underlying mechanism of miR-1827 in tumor suppression. PMID- 26840031 TI - Painful Diabetic Neuropathy Anxiety Rasch-Transformed Questionnaire (PART Q30((c)) ). AB - The association between painful diabetic neuropathy (PDN) and anxiety has been acknowledged using various anxiety scales capturing various fear entities. It has never been examined whether these generally applied anxiety questionnaires could be pooled to construct one overall anxiety metric. After completion by a cohort of 151 patients with PDN, data obtained from seven generally applied fear scales were stacked (n = 88 items) and subjected to Rasch analyses (pre-PART-Q88) to create the PDN overall Anxiety Questionnaire (PART-Q30((c)) ). We subsequently examined the impact of the final constructed PART-Q30((c)) on disability and Quality of Life (QoL) using the Rasch-Transformed Pain Disability Index (RT-PDI) and the Norfolk Quality of Life Questionnaire, Diabetic Neuropathy version (RT Norfolk). The pre-PART-Q88 data did not meet Rasch model's expectations. Through stepwise examination for model fit, disordered thresholds, local dependency and item bias, we succeeded in reducing the data and constructing a 30 items overall anxiety scale (PART-Q30((c)) ) that fulfilled all model's expectations, including unidimensionality. An acceptable internal reliability was found (person separation-index: 0.90). PART-Q30((c)) explained 36% of disability and combined with RT-PDI 63% of QoL (assessed with RT-Norfolk). PMID- 26840032 TI - Sexuality-related issues in borderline personality disorder: A comprehensive review. AB - OBJECTIVE: Sexuality is somewhat neglected in clinical research on borderline personality disorder (BPD). METHOD: We performed a systematic review from 1980 to November 2014 through PubMed and PsycINFO. RESULTS: Empirical evidence underscores that childhood sexual trauma may be considered a non-specific risk factor for BPD. Furthermore, individuals with BPD also display higher sexual identity disturbances and homosexual relationships than non-BPD individuals. Moreover, patients with BPD also exhibit higher sexual impulsivity than non-BPD. In addition, sexual risk behaviours among individuals with BPD are related to increased rates of sexually transmitted diseases, unwanted pregnancies, rape and commercial sexual relationships, especially among drug abusers. Although psychotherapy is widely recommended for BPD, there has been little systematic research on the effect of these treatments with respect to co-morbid post traumatic symptoms related to childhood sexual trauma. CONCLUSIONS: Sexuality related issues represent a major clinical topic within this population. Findings are discussed concerning their methodological limitations and clinical implications. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26840033 TI - Extensive Overgrowth of Sex Cord-Like Differentiation in Uterine Mullerian Adenosarcoma: A Rare and Challenging Entity. AB - Sex cord-like differentiation has been well documented in endometrial stromal tumors. On the basis of the extent of sex cord differentiation, uterine stromal tumors with this kind of differentiation have been classified into 2 subgroups of endometrial stromal tumor with sex cord-like elements and uterine tumors resembling ovarian sex cord tumor. When extensive, this differentiation has been accompanied with indolent clinical behavior and rather good prognosis in most cases. Sex cord differentiation has been rarely observed in uterine mullerian adenosarcoma. Only 3 cases of such occurrence have been reported in the English literature. Herein, we report a case of uterine mullerian adenosarcoma extensively overgrown by uterine tumor resembling ovarian sex cord tumor in a young woman. The presence of an ovarian sex cord tumor component has been confirmed by immunohistochemistry. To the best of our knowledge, this is the second report of such a case in the English literature. PMID- 26840030 TI - O-GlcNAcylation of protein kinase A catalytic subunits enhances its activity: a mechanism linked to learning and memory deficits in Alzheimer's disease. AB - Alzheimer's disease (AD) is characterized clinically by memory loss and cognitive decline. Protein kinase A (PKA)-CREB signaling plays a critical role in learning and memory. It is known that glucose uptake and O-GlcNAcylation are reduced in AD brain. In this study, we found that PKA catalytic subunits (PKAcs) were posttranslationally modified by O-linked N-acetylglucosamine (O-GlcNAc). O GlcNAcylation regulated the subcellular location of PKAcalpha and PKAcbeta and enhanced their kinase activity. Upregulation of O-GlcNAcylation in metabolically active rat brain slices by O-(2-acetamido-2-deoxy-d-glucopyranosylidenamino) N phenylcarbamate (PUGNAc), an inhibitor of N-acetylglucosaminidase, increased the phosphorylation of tau at the PKA site, Ser214, but not at the non-PKA site, Thr205. In contrast, in rat and mouse brains, downregulation of O-GlcNAcylation caused decreases in the phosphorylation of CREB at Ser133 and of tau at Ser214, but not at Thr205. Reduction in O-GlcNAcylation through intracerebroventricular injection of 6-diazo-5-oxo-l-norleucine (DON), the inhibitor of glutamine fructose-6-phosphate amidotransferase, suppressed PKA-CREB signaling and impaired learning and memory in mice. These results indicate that in addition to cAMP and phosphorylation, O-GlcNAcylation is a novel mechanism that regulates PKA-CREB signaling. Downregulation of O-GlcNAcylation suppresses PKA-CREB signaling and consequently causes learning and memory deficits in AD. PMID- 26840034 TI - The Polyembryoma: One of the Most Intriguing Human Neoplasms, With Comments on the Investigator Who Brought it to Light, Albert Peyron. PMID- 26840035 TI - Long-term salinity tolerance is accompanied by major restructuring of the coral bacterial microbiome. AB - Scleractinian corals are assumed to be stenohaline osmoconformers, although they are frequently subjected to variations in seawater salinity due to precipitation, freshwater run-off and other processes. Observed responses to altered salinity levels include differences in photosynthetic performance, respiration and increased bleaching and mortality of the coral host and its algal symbiont, but a study looking at bacterial community changes is lacking. Here, we exposed the coral Fungia granulosa to strongly increased salinity levels in short- and long term experiments to disentangle temporal and compartment effects of the coral holobiont (i.e. coral host, symbiotic algae and associated bacteria). Our results show a significant reduction in calcification and photosynthesis, but a stable microbiome after short-term exposure to high-salinity levels. By comparison, long term exposure yielded unchanged photosynthesis levels and visually healthy coral colonies indicating long-term acclimation to high-salinity levels that were accompanied by a major coral microbiome restructuring. Importantly, a bacterium in the family Rhodobacteraceae was succeeded by Pseudomonas veronii as the numerically most abundant taxon. Further, taxonomy-based functional profiling indicates a shift in the bacterial community towards increased osmolyte production, sulphur oxidation and nitrogen fixation. Our study highlights that bacterial community composition in corals can change within days to weeks under altered environmental conditions, where shifts in the microbiome may enable adjustment of the coral to a more advantageous holobiont composition. PMID- 26840036 TI - Reduction of diuretics and analysis of water and muscle volumes to prevent falls and fall-related fractures in older adults. AB - AIM: In an attempt to decrease the incidence of falls and fall-related fractures at a special geriatric nursing home, we endeavored to reduce diuretic doses, and examined the relationship between the effectiveness of this approach with the body compositions and activities of daily living of the study cohort. METHODS: We enrolled 93 participants living in the community, 60 residents of an intermediate geriatric nursing home and 50 residents of the 100-bed Kandayama Yasuragien special geriatric nursing home. We recorded body composition using a multifrequency bioelectrical impedance analyzer. Daily loop diuretic and other diuretic regimens of those in the special geriatric nursing home were reduced or replaced with "NY-mode" diuretic therapy, namely, spironolactone 12.5 mg orally once on alternate days. RESULTS: The incidence of falls fell from 53 in 2011 to 29 in 2012, and there were no fall-related proximal femoral fractures for 3 years after the introduction of NY-mode diuretic therapy. We also found statistically significant differences in muscle and intracellular water volumes in our elderly participants: those with higher care requirements or lower levels of independence had lower muscle or water volumes. CONCLUSIONS: We found that reducing or replacing daily diuretics with NY-mode therapy appeared to reduce the incidence of falls and fall-related proximal femoral fracture, likely by preserving intracellular and extracellular body water volumes. Low-dose spironolactone (12.5 mg on alternate days) appears to be an effective means of treating elderly individuals with chronic heart failure or other edematous states, while preventing falls and fall-related fractures. Geriatr Gerontol Int 2017; 17: 262 269. PMID- 26840037 TI - Diet, microbiota, and dysbiosis: a 'recipe' for colorectal cancer. AB - The food we consume feeds not only us, but also a vast and diverse community of microbiota within our gastrointestinal tract. In a process of symbiotic co evolution, the gut microbiota became essential for the maintenance of the health and integrity of our colon. The advent of next-generation DNA sequencing technology and metabolic profiling have, in the recent years, revealed the remarkable complexity of microbial diversity and function, and that the microbiota produce a wide variety of bioactive products that are not only active at the mucosal surface, but also absorbed and circulated throughout the body, influencing distant organ health and function. As a result, several microbiota compositional patterns and their associations with both health and disease states have been identified. Importantly, a disturbed microbiota-host relationship, termed dysbiosis, is now recognized to be the root cause for a growing list of diseases, including colorectal cancer (CRC). There is mounting in vitro and in vivo evidence to suggest that diet selects for the microbiota composition and several health promoting and deleterious effects of diet are, in fact, mediated by the microbiota. Recent findings of the feasibility of dietary fiber to boost the colonic microbial synthesis of anti-proliferative and counter carcinogenic metabolites, particularly butyrate, underscores the prerequisite of dietary modification as a key measure to curb the pandemic of CRC in westernized countries. Better understanding of the diet-microbiota interplay and large-scale studies to evaluate the efficacy of dietary modification and gut microbiota modulation in reversing dysbiosis and restoring health could offer novel preventative and/or therapeutic strategies against westernized diseases, which are now considered the chief threat to public health. PMID- 26840040 TI - Mixed Quantum-Classical Study of Nonadiabatic Curve Crossing in Condensed Phases. AB - We apply the mixed quantum-classical Liouville (MQCL) equation to investigate the nonadiabatic curve crossing in condensed phases. More specifically, electron transfer rate constants of the spin-Boson model are calculated by employing a rate constant expression using the collective solvent polarization as the reaction coordinate. In the calculation, classical nuclear degrees of freedom are initially sampled at the transition state configuration, and the initial state for the electronic degree of freedom is obtained from a mixed quantum-classical Boltzmann distribution. Different contributions to the electron transfer rate from the diagonal and off-diagonal elements of the initial density matrix, and contributions from trajectories with positive and negative initial velocities are analyzed. It is shown that the off-diagonal elements of the initial density matrix play an important role in the total electron transfer rate. The MQCL results are also compared with those calculated using Ehrenfest dynamics. It is found that, although the Ehrenfest dynamics is inaccurate when the reactive flux rate expression is used directly, it can give reasonably accurate results when individual contributions from the diagonal and off-diagonal elements of the initial density matrix are calculated. PMID- 26840038 TI - Association of fasting glucose levels with incident atherosclerotic cardiovascular disease: An 8-year follow-up study in a Chinese population. AB - BACKGROUND: Identification of the population at high risk of developing atherosclerotic cardiovascular disease (ASCVD) is critical for its prevention. The aim of the present study was to evaluate the use of fasting blood glucose (FBG) to predict ASCVD. METHODS: In all, 18 610 participants, aged 35-74 years at enrollment, were included in this prospective study. Baseline information was collected using a standardized questionnaire, physical examinations, and laboratory tests. During follow-up, disease status and vital information were updated. Cox proportional hazards regression analysis was used to estimate associations, with normal FBG (70-99 mg/dL) as the reference group. Anthropometric measurements, socioeconomic status, and conventional cardiovascular risk factors were included in the multivariate-adjusted model. RESULTS: After 7.8 years follow-up (145 223 person-years), there were 519 cases of ASCVD. The multivariate-adjusted hazard ratios (HR), with 95% confidence intervals (CI), for ASCVD in patients with low FBG (<70 mg/dL), impaired fasting glucose (IFG; 100-125 mg/dL), and diabetes (>=126 mg/dL, use of antidiabetic medication and/or self-report) were 1.35 (0.84, 2.15), 1.02 (0.81, 1.27), and 1.68 (1.26, 2.23), respectively. Although IFG was associated with the development of diabetes (multivariate-adjusted HR 3.67; 95% CI 3.20, 4.21), it was only associated with incident ASCVD in the univariate model (HR 1.52; 95% CI 1.23, 1.88). The association of diabetes with coronary heart disease was more pronounced than that with stroke. Gender and residential differences were also identified. CONCLUSIONS: In the present study, IFG was associated with the development of diabetes but not incident ASCVD. Prevention strategies to reduce the development of diabetes in people with IFG are critical to improve cardiovascular health. PMID- 26840041 TI - Is Hormone Replacement Therapy Safe in Women With a BRCA Mutation?: A Systematic Review of the Contemporary Literature. AB - OBJECTIVES: Women with a BRCA1 or BRCA2 mutation are recommended to undergo prophylactic (or risk reducing) bilateral salpingo-oophorectomy (BSO) before age 40, resulting in surgical menopause. Given the concerns of estrogen deprivation on overall health, hormone therapy (HT) is often discussed, yet safety concerns persist. MATERIALS AND METHODS: We performed a systematic literature review of the safety of HT in women with a BRCA mutation undergoing prophylactic BSO. RESULTS: Although there remains a paucity of data on this topic, as evidenced by this systematic review of the contemporary literature, these patients do benefit from treatment, especially as it relates to menopausal symptoms without an apparently increased risk of breast cancer. CONCLUSIONS: Decisions regarding the use of HT in women who undergo BSO after detection of a BRCA mutation must be individualized based on careful consideration of the risks and benefits. However, the risks of a subsequent cancer diagnosis appear small, particularly in regards to the benefits of treatment afforded by HT. PMID- 26840039 TI - High glucose concentration induces endothelial cell proliferation by regulating cyclin-D2-related miR-98. AB - Cyclin D2 is involved in the pathology of vascular complications of type 2 diabetes mellitus (T2DM). This study investigated the role of cyclin-D2-regulated miRNAs in endothelial cell proliferation of T2DM. Results showed that higher glucose concentration (4.5 g/l) significantly promoted the proliferation of rat aortic endothelial cells (RAOECs), and significantly increased the expression of cyclin D2 and phosphorylation of retinoblastoma 1 (p-RB1) in RAOECs compared with those under low glucose concentration. The cyclin D2-3' untranslated region is targeted by miR-98, as demonstrated by miRNA analysis software. Western blot also confirmed that cyclin D2 and p-RB1 expression was regulated by miR-98. The results indicated that miR-98 treatment can induce RAOEC apoptosis. The suppression of RAOEC growth by miR-98 might be related to regulation of Bcl-2, Bax and Caspase 9 expression. Furthermore, the expression levels of miR-98 decreased in 4.5 g/l glucose-treated cells compared with those treated by low glucose concentration. Similarly, the expression of miR-98 significantly decreased in aortas of established streptozotocin (STZ)-induced diabetic rat model compared with that in control rats; but cyclin D2 and p-RB1 levels remarkably increased in aortas of STZ-induced diabetic rats compared with those in healthy control rats. In conclusion, this study demonstrated that high glucose concentration induces cyclin D2 up-regulation and miR-98 down-regulation in the RAOECs. By regulating cyclin D2, miR-98 can inhibit human endothelial cell growth, thereby providing novel therapeutic targets for vascular complication of T2DM. PMID- 26840042 TI - Glycosaminoglycan-Mimetic Signals Direct the Osteo/Chondrogenic Differentiation of Mesenchymal Stem Cells in a Three-Dimensional Peptide Nanofiber Extracellular Matrix Mimetic Environment. AB - Recent efforts in bioactive scaffold development focus strongly on the elucidation of complex cellular responses through the use of synthetic systems. Designing synthetic extracellular matrix (ECM) materials must be based on understanding of cellular behaviors upon interaction with natural and artificial scaffolds. Hence, due to their ability to mimic both the biochemical and mechanical properties of the native tissue environment, supramolecular assemblies of bioactive peptide nanostructures are especially promising for development of bioactive ECM-mimetic scaffolds. In this study, we used glycosaminoglycan (GAG) mimetic peptide nanofiber gel as a three-dimensional (3D) platform to investigate how cell lineage commitment is altered by external factors. We observed that amount of fetal bovine serum (FBS) presented in the cell media had synergistic effects on the ability of GAG-mimetic nanofiber gel to mediate the differentiation of mesenchymal stem cells into osteogenic and chondrogenic lineages. In particular, lower FBS concentration in the culture medium was observed to enhance osteogenic differentiation while higher amount FBS promotes chondrogenic differentiation in tandem with the effects of the GAG-mimetic 3D peptide nanofiber network, even in the absence of externally administered growth factors. We therefore demonstrate that mesenchymal stem cell differentiation can be specifically controlled by the combined influence of growth medium components and a 3D peptide nanofiber environment. PMID- 26840043 TI - A juvenile-adult population model: climate change, cannibalism, reproductive synchrony, and strong Allee effects. AB - We study a discrete time, structured population dynamic model that is motivated by recent field observations concerning certain life history strategies of colonial-nesting gulls, specifically the glaucous-winged gull (Larus glaucescens). The model focuses on mechanisms hypothesized to play key roles in a population's response to degraded environment resources, namely, increased cannibalism and adjustments in reproductive timing. We explore the dynamic consequences of these mechanics using a juvenile-adult structure model. Mathematically, the model is unusual in that it involves a high co-dimension bifurcation at [Formula: see text] which, in turn, leads to a dynamic dichotomy between equilibrium states and synchronized oscillatory states. We give diagnostic criteria that determine which dynamic is stable. We also explore strong Allee effects caused by positive feedback mechanisms in the model and the possible consequence that a cannibalistic population can survive when a non cannibalistic population cannot. PMID- 26840044 TI - Somatic mutations rather than viral infection classify focal cortical dysplasia type II as mTORopathy. AB - PURPOSE OF REVIEW: Genetic studies in focal cortical dysplasia type II (FCD II) provided ample evidence for somatic mutations in genes associated with the mammalian target of rapamycin (mTOR) pathway. Interestingly, the mTOR pathway can also be activated by the E6 oncogene of human papilloma viruses, and available data in FCD II remain controversial. We review and discuss the contradicting etiologies. RECENT FINDINGS: The neuroembryologic basis of cortical development and timing of a somatic mutation occurring in proliferating neuroblasts can mechanistically link mTORopathies. When a somatic mutation occurs in proliferating neuroblasts at an early stage of their anticipated total number of 33 mitotic cell cycles, large hemispheric lesions will develop from their affected progeny. Somatic mutations occurring at later periods of neuroblast expansion will result in circumscribed and small FCD II. Recently published data did not support evidence for viral infection in FCD II. SUMMARY: Genetic and histopathological data rather than viral infection classify FCD II into the spectrum of mTORopathies. Size and extent of the resulting cerebral lesion can be well explained by timing of somatic mutations during cortical development. PMID- 26840045 TI - Psychiatric comorbidities in neurodevelopmental disorders. AB - PURPOSE OF REVIEW: Recent changes in the diagnostic criteria for psychiatric and neurodevelopmental disorders as well as increases in the prevalence of both have elevated the focus on these areas of medicine and their clinical overlap. RECENT FINDINGS: Several recent studies have examined psychiatric comorbidities in neurodevelopmental disorders including autism and specific genetic syndromes. A growing number of reports underscore the genetic overlap between previously distinct clinical disorders. Behavioral and psychiatric features are increasingly identified in association with intellectual developmental disorders. SUMMARY: As there have been advances in our collective understanding of the genetic underpinnings of certain disorders and the downstream physiological consequences of those genetic alterations, challenges to the way boundaries have been drawn around psychiatric disorders, and by extension, the concept of comorbidity, warrant review. PMID- 26840046 TI - miR-133b Reverses the Hydrosalpinx-induced Impairment of Embryo Attachment Through Down-regulation of SGK1. AB - CONTEXT: Hydrosalpinx impairs endometrial receptivity and embryo implantation. However, the exact underlying mechanism remains elusive. OBJECTIVE: This study aimed to explore how an miR-133b-mediated mechanism controls endometrial receptivity and embryo attachment in the endometrium of women with hydrosalpinx. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: Ishikawa cells were treated with hydrosalpinx fluid (HF) from infertile patients and cultured for in vitro analysis. The attachment rates of BeWo spheroids and mouse embryos to Ishikawa cells were assayed. PRIMARY OUTCOME MEASURE: miR-133b, serum and glucocorticoid regulated kinase 1 (SGK1), and homeobox A10 (HOXA10) expression levels were evaluated by quantitative real-time PCR and Western blot assays. RESULTS: The expression of miR-133b and HOXA10 was significantly down-regulated, whereas the miR-133b target gene SGK1 was up-regulated in mid-secretory endometrial tissues of women with hydrosalpinx and in HF-treated Ishikawa cells. Moreover, hydrosalpinx inhibited miR-133b expression through the activation of nuclear factor kappaB/p65, and SGK1 decreased miR-133b-induced HOXA10 expression by phosphorylating cAMP responsive element binding protein in Ishikawa cells. Our results also showed that miR-133b and HOXA10 contributed to BeWo spheroid adhesiveness, whereas SGK1 inhibited BeWo spheroid attachment to Ishikawa cells. Importantly, miR-133b overexpression reversed the HF-mediated impairment of embryo attachment in vitro. CONCLUSIONS: miR-133b directly targets SGK1 to reverse the hydrosalpinx-induced down-regulation of HOXA10 and to attenuate the impairment of embryo attachment in vitro. PMID- 26840048 TI - Norman E. McSwain, Jr., MD, FACS (1937-2015). PMID- 26840047 TI - IGSF1 Deficiency: Lessons From an Extensive Case Series and Recommendations for Clinical Management. AB - CONTEXT: Mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene cause the X-linked IGSF1 deficiency syndrome consisting of central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasionally transient partial GH deficiency. Since our first reports, we discovered 20 new families with 18 new pathogenic IGSF1 mutations. OBJECTIVE: We aimed to share data on the largest cohort of patients with IGSF1 deficiency to date and formulate recommendations for clinical management. METHODS: We collected clinical and biochemical characteristics of 69 male patients (35 children, 34 adults) and 56 female IGSF1 mutation carriers (three children, 53 adults) from 30 unrelated families according to a standardized clinical protocol. At evaluation, boys were treated with levothyroxine in 89%, adult males in 44%, and females in 5% of cases. RESULTS: Additional symptoms in male patients included small thyroid gland volume (74%), high birth weight (25%), and large head circumference (20%). In general, the timing of pubertal testicular growth was normal or even premature, in contrast to a late rise in T levels. Late adrenarche was observed in patients with prolactin deficiency, and adult dehydroepiandrosterone concentrations were decreased in 40%. Hypocortisolism was observed in 6 of 28 evaluated newborns, although cortisol concentrations were normal later. Waist circumference of male patients was increased in 60%, but blood lipids were normal. Female carriers showed low free T4 (FT4) and low-normal FT4 in 18% and 60%, respectively, delayed age at menarche in 31%, mild prolactin deficiency in 22%, increased waist circumference in 57%, and a negative correlation between FT4 concentrations and metabolic parameters. CONCLUSION: IGSF1 deficiency represents the most common genetic cause of central hypothyroidism and is associated with multiple other characteristics. Based on these results, we provide recommendations for mutational analysis, endocrine work up, and long-term care. PMID- 26840049 TI - Active machine learning-driven experimentation to determine compound effects on protein patterns. AB - High throughput screening determines the effects of many conditions on a given biological target. Currently, to estimate the effects of those conditions on other targets requires either strong modeling assumptions (e.g. similarities among targets) or separate screens. Ideally, data-driven experimentation could be used to learn accurate models for many conditions and targets without doing all possible experiments. We have previously described an active machine learning algorithm that can iteratively choose small sets of experiments to learn models of multiple effects. We now show that, with no prior knowledge and with liquid handling robotics and automated microscopy under its control, this learner accurately learned the effects of 48 chemical compounds on the subcellular localization of 48 proteins while performing only 29% of all possible experiments. The results represent the first practical demonstration of the utility of active learning-driven biological experimentation in which the set of possible phenotypes is unknown in advance. PMID- 26840052 TI - Temperature-Dependent Mean Free Path Spectra of Thermal Phonons Along the c-Axis of Graphite. AB - Heat conduction in graphite has been studied for decades because of its exceptionally large thermal anisotropy. While the bulk thermal conductivities along the in-plane and cross-plane directions are well-known, less understood are the microscopic properties of the thermal phonons responsible for heat conduction. In particular, recent experimental and computational works indicate that the average phonon mean free path (MFP) along the c-axis is considerably larger than that estimated by kinetic theory, but the distribution of MFPs remains unknown. Here, we report the first quantitative measurements of c-axis phonon MFP spectra in graphite at a variety of temperatures using time-domain thermoreflectance measurements of graphite flakes with variable thickness. Our results indicate that c-axis phonon MFPs have values of a few hundred nanometers at room temperature and a much narrower distribution than in isotropic crystals. At low temperatures, phonon scattering is dominated by grain boundaries separating crystalline regions of different rotational orientation. Our study provides important new insights into heat transport and phonon scattering mechanisms in graphite and other anisotropic van der Waals solids. PMID- 26840051 TI - Novel origin of lamin-derived cytoplasmic intermediate filaments in tardigrades. AB - Intermediate filament (IF) proteins, including nuclear lamins and cytoplasmic IF proteins, are essential cytoskeletal components of bilaterian cells. Despite their important role in protecting tissues against mechanical force, no cytoplasmic IF proteins have been convincingly identified in arthropods. Here we show that the ancestral cytoplasmic IF protein gene was lost in the entire panarthropod (onychophoran + tardigrade + arthropod) rather than arthropod lineage and that nuclear, lamin-derived proteins instead acquired new cytoplasmic roles at least three times independently in collembolans, copepods, and tardigrades. Transcriptomic and genomic data revealed three IF protein genes in the tardigrade Hypsibius dujardini, one of which (cytotardin) occurs exclusively in the cytoplasm of epidermal and foregut epithelia, where it forms belt-like filaments around each epithelial cell. These results suggest that a lamin derivative has been co-opted to enhance tissue stability in tardigrades, a function otherwise served by cytoplasmic IF proteins in all other bilaterians. PMID- 26840050 TI - Localized epigenetic silencing of a damage-activated WNT enhancer limits regeneration in mature Drosophila imaginal discs. AB - Many organisms lose the capacity to regenerate damaged tissues as they mature. Damaged Drosophila imaginal discs regenerate efficiently early in the third larval instar (L3) but progressively lose this ability. This correlates with reduced damage-responsive expression of multiple genes, including the WNT genes wingless (wg) and Wnt6. We demonstrate that damage-responsive expression of both genes requires a bipartite enhancer whose activity declines during L3. Within this enhancer, a damage-responsive module stays active throughout L3, while an adjacent silencing element nucleates increasing levels of epigenetic silencing restricted to this enhancer. Cas9-mediated deletion of the silencing element alleviates WNT repression, but is, in itself, insufficient to promote regeneration. However, directing Myc expression to the blastema overcomes repression of multiple genes, including wg, and restores cellular responses necessary for regeneration. Localized epigenetic silencing of damage-responsive enhancers can therefore restrict regenerative capacity in maturing organisms without compromising gene functions regulated by developmental signals. PMID- 26840053 TI - Chronic Hypoxia Accentuates Dysanaptic Lung Growth. AB - RATIONALE: Adults born and raised at high altitudes have larger lung volumes and greater pulmonary diffusion capacity compared with adults at low altitude; however, it remains unclear whether the air and tissue volumes have comparable increases and whether there is a difference in airway size. OBJECTIVES: To assess the effect of chronic hypoxia on lung growth using in vivo high-resolution computed tomography measurements. METHODS: Healthy adults born and raised at moderate altitude (2,000 m above sea level; n = 19) and at low altitude (400 m above sea level; n = 23) underwent high-resolution computed tomography. Differences in total lung, air, and tissue volume, mean lung density, as well as airway lumen and wall areas in anatomically matched airways were compared between groups. MEASUREMENTS AND MAIN RESULTS: No significant differences for age, sex, weight, or height were found between the two groups (P > 0.05). In a multivariate regression model, altitude was a significant contributor for total lung volume (P = 0.02), air volume (P = 0.03), and tissue volume (P = 0.03), whereby the volumes were greater for the moderate- versus the low-altitude group. However, altitude was not a significant contributor for mean lung density (P = 0.35) or lumen and wall areas in anatomically matched segmental, subsegmental, and subsubsegmental airways. CONCLUSIONS: Our findings suggest that the adult lung did not increase lung volume later in life by expansion of an existing number of alveoli, but rather from increased alveolarization early in life. In addition, chronic hypoxia accentuates dysanaptic lung growth by increasing the lung parenchyma but not the airways. PMID- 26840054 TI - Resistance Training in Spontaneously Hypertensive Rats with Severe Hypertension. AB - BACKGROUND: Resistance training (RT) has been recommended as a non pharmacological treatment for moderate hypertension. In spite of the important role of exercise intensity on training prescription, there is still no data regarding the effects of RT intensity on severe hypertension (SH). OBJECTIVE: This study examined the effects of two RT protocols (vertical ladder climbing), performed at different overloads of maximal weight carried (MWC), on blood pressure (BP) and muscle strength of spontaneously hypertensive rats (SHR) with SH. METHODS: Fifteen male SHR ENT#091;206 +/- 10 mmHg of systolic BP (SBP)ENT#093; and five Wistar Kyoto rats (WKY; 119 +/- 10 mmHg of SBP) were divided into 4 groups: sedentary (SED-WKY) and SHR (SED-SHR); RT1-SHR training relative to body weight (~40% of MWC); and RT2-SHR training relative to MWC test (~70% of MWC). Systolic BP and heart rate (HR) were measured weekly using the tail-cuff method. The progression of muscle strength was determined once every fifteen days. The RT consisted of 3 weekly sessions on non-consecutive days for 12-weeks. RESULTS: Both RT protocols prevented the increase in SBP (delta - 5 and -7 mmHg, respectively; p > 0.05), whereas SBP of the SED-SHR group increased by 19 mmHg (p < 0.05). There was a decrease in HR only for the RT1 group (p < 0.05). There was a higher increase in strength in the RT2 (140%; p < 0.05) group as compared with RT1 (11%; p > 0.05). CONCLUSIONS: Our data indicated that both RT protocols were effective in preventing chronic elevation of SBP in SH. Additionally, a higher RT overload induced a greater increase in muscle strength. PMID- 26840055 TI - Prognostic Value of Pulmonary Vascular Resistance by Magnetic Resonance in Systolic Heart Failure. AB - BACKGROUND: Pulmonary hypertension is associated with poor prognosis in heart failure. However, non-invasive diagnosis is still challenging in clinical practice. OBJECTIVE: We sought to assess the prognostic utility of non-invasive estimation of pulmonary vascular resistances (PVR) by cardiovascular magnetic resonance to predict adverse cardiovascular outcomes in heart failure with reduced ejection fraction (HFrEF). METHODS: Prospective registry of patients with left ventricular ejection fraction (LVEF) < 40% and recently admitted for decompensated heart failure during three years. PVR were calculated based on right ventricular ejection fraction and average velocity of the pulmonary artery estimated during cardiac magnetic resonance. Readmission for heart failure and all-cause mortality were considered as adverse events at follow-up. RESULTS: 105 patients (average LVEF 26.0 +/- 7.7%, ischemic etiology 43%) were included. Patients with adverse events at long-term follow-up had higher values of PVR (6.93 +/- 1.9 vs. 4.6 +/- 1.7 estimated Wood Units (eWu), p < 0.001). In multivariate Cox regression analysis, PVR >= 5 eWu(cutoff value according to ROC curve) was independently associated with increased risk of adverse events at 9 months follow-up (HR2.98; 95% CI 1.12-7.88; p < 0.03). CONCLUSIONS: In patients with HFrEF, the presence of PVR >= 5.0 Wu is associated with significantly worse clinical outcome at follow-up. Non-invasive estimation of PVR by cardiac magnetic resonance might be useful for risk stratification in HFrEF, irrespective of etiology, presence of late gadolinium enhancement or LVEF. PMID- 26840057 TI - Addition to "Total Synthesis of Linckosides A and B, the Representative Starfish Polyhydroxysteroid Glycosides with Neuritogenic Activities". PMID- 26840056 TI - Very Long-Term Prognostic Role of Admission BNP in Non-ST Segment Elevation Acute Coronary Syndrome. AB - BACKGROUND: BNP has been extensively evaluated to determine short- and intermediate-term prognosis in patients with acute coronary syndrome, but its role in long-term mortality is not known. OBJECTIVE: To determine the very long term prognostic role of B-type natriuretic peptide (BNP) for all-cause mortality in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). METHODS: A cohort of 224 consecutive patients with NSTEACS, prospectively seen in the Emergency Department, had BNP measured on arrival to establish prognosis, and underwent a median 9.34-year follow-up for all-cause mortality. RESULTS: Unstable angina was diagnosed in 52.2%, and non-ST segment elevation myocardial infarction, in 47.8%. Median admission BNP was 81.9 pg/mL (IQ range = 22.2; 225) and mortality rate was correlated with increasing BNP quartiles: 14.3; 16.1; 48.2; and 73.2% (p < 0.0001). ROC curve disclosed 100 pg/mL as the best BNP cut off value for mortality prediction (area under the curve = 0.789, 95% CI= 0.723 0.854), being a strong predictor of late mortality: BNP < 100 = 17.3% vs. BNP >= 100 = 65.0%, RR = 3.76 (95% CI = 2.49-5.63, p < 0.001). On logistic regression analysis, age >72 years (OR = 3.79, 95% CI = 1.62-8.86, p = 0.002), BNP >= 100 pg/mL (OR = 6.24, 95% CI = 2.95-13.23, p < 0.001) and estimated glomerular filtration rate (OR = 0.98, 95% CI = 0.97-0.99, p = 0.049) were independent late mortality predictors. CONCLUSIONS: BNP measured at hospital admission in patients with NSTEACS is a strong, independent predictor of very long-term all-cause mortality. This study allows raising the hypothesis that BNP should be measured in all patients with NSTEACS at the index event for long-term risk stratification. PMID- 26840059 TI - Tinman Regulates NetrinB in the Cardioblasts of the Drosophila Dorsal Vessel. AB - Morphogenesis of the Drosophila dorsal vessel (DV) shares similarities with that of the vertebrate heart. Precursors line up at both sides of the embryo, migrate towards the midline and fuse to form a tubular structure. Guidance receptors and their ligands have been implicated in this process in vertebrates and invertebrates, as have been a series of evolutionarily conserved cardiogenic transcriptional regulators including Tinman, the Drosophila homolog of the transcription factor Nkx-2.5. NetrinB (NetB), a repulsive ligand for the Unc-5 receptor is required to preserve the dorsal vessel hollow. It localizes to the luminal space of the dorsal vessel but its source and its regulation is unknown. Here, using genetics together with in situ hybridization with single cell resolution, we show how tin is required for NetrinB expression in cardioblasts during DV tubulogenesis and sufficient to promote NetB transcription ectopically. We further identify a dorsal vessel-specific NetB enhancer and show that it is also regulated by tin in a similar fashion to NetB. PMID- 26840058 TI - Adipose-Derived Mesenchymal Stem Cells Restore Impaired Mucosal Immune Responses in Aged Mice. AB - It has been shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into adipocytes, chondrocytes and osteoblasts. Several clinical trials have shown the ability of AMSCs to regenerate these differentiated cell types. Age-associated dysregulation of the gastrointestinal (GI) immune system has been well documented. Our previous studies showed that impaired mucosal immunity in the GI tract occurs earlier during agingthan is seen in the systemic compartment. In this study, we examined the potential of AMSCs to restore the GI mucosal immune system in aged mice. Aged (>18 mo old) mice were adoptively transferred with AMSCs. Two weeks later, mice were orally immunized with ovalbumin (OVA) plus cholera toxin (CT) three times at weekly intervals. Seven days after the final immunization, when fecal extract samples and plasma were subjected to OVA- and CT-B-specific ELISA, elevated levels of mucosal secretory IgA (SIgA) and plasma IgG antibody (Ab) responses were noted in aged mouse recipients. Similar results were also seen aged mice which received AMSCs at one year of age. When cytokine production was examined, OVA-stimulated Peyer's patch CD4+ T cells produced increased levels of IL-4. Further, CD4+ T cells from the lamina propria revealed elevated levels of IL-4 and IFN-gamma production. In contrast, aged mice without AMSC transfer showed essentially no OVA- or CT-B specific mucosal SIgA or plasma IgG Ab or cytokine responses. Of importance, fecal extracts from AMSC transferred aged mice showed neutralization activity to CT intoxication. These results suggest that AMSCs can restore impaired mucosal immunity in the GI tract of aged mice. PMID- 26840060 TI - Immunogenicity, effectiveness and safety of combined hepatitis A and B vaccine: a systematic literature review. AB - BACKGROUND: Hepatitis A and B are two of the most common vaccine-preventable diseases and vaccination for Hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for those at risk of contracting HAV and/or HBV through their occupation, travel or lifestyle. OBJECTIVE: To describe the vaccine efficacy, immunogenicity, effectiveness and safety of the combined vaccine against hepatitis A and hepatitis B. METHODS: A systematic review of the literature published between 1990 and 2015. RESULTS: Anti-HAV seropositivity rates ranged from 96.2% to 100% and anti-HBs seroprotection rates from 82% to 100%. Antibodies persisted up to 15 years and geometric mean concentration (GMC) remained above the seropositivity cut-off value for both. Anti-HAV and anti-HBs immune responses were lower in less immunocompetent individuals one month after completion of the immunization schedule. The safety profiles of Twinrix(TM) and monovalent hepatitis A and B vaccines were similar. CONCLUSION: The vaccine offers satisfactory long-term immunogenicity rates, expected duration of protection and safety profile similar to the monovalent hepatitis A or B vaccines. PMID- 26840061 TI - The Cadillac Tax--A Crucial Tool for Delivery-System Reform. PMID- 26840062 TI - Correction: Microbiome Profiles in Periodontitis in Relation to Host and Disease Characteristics. PMID- 26840063 TI - A Transition from Localized to Strongly Correlated Electron Behavior and Mixed Valence Driven by Physical or Chemical Pressure in ACo2As2 (A = Eu and Ca). AB - We demonstrate that the action of physical pressure, chemical compression, or aliovalent substitution in ACo2As2 (A = Eu and Ca) has a general consequence of causing these antiferromagnetic materials to become ferromagnets. In all cases, the mixed valence triggered at the electropositive A site results in the increase of the Co 3d density of states at the Fermi level. Remarkably, the dramatic alteration of magnetic behavior results from the very minor (<0.15 electron) change in the population of the 3d orbitals. The mixed valence state of Eu observed in the high-pressure (HP) form of EuCo2As2 exhibits a remarkable stability, achieving the average oxidation state of +2.25 at 12.6 GPa. In the case of CaCo2As2, substituting even 10% of Eu or La into the Ca site causes ferromagnetic ordering of Co moments. Similar to HP-EuCo2As2, the itinerant 3d ferromagnetism emerges from electronic doping into the Co layer because of chemical compression of Eu sites in Ca0.9Eu0.1Co1.91As2 or direct electron doping in Ca0.85La0.15Co1.89As2. The results reported herein demonstrate the general possibility of amplifying minor localized electronic effects to achieve major changes in material's properties via involvement of strongly correlated electrons. PMID- 26840065 TI - Correction to Detection of Tetrodotoxins in Puffer Fish by a Self-Assembled Monolayer-Based Immunoassay and Comparison with Surface Plasmon Resonance, LC MS/MS, and Mouse Bioassay. PMID- 26840064 TI - Effects of MDMA Injections on the Behavior of Socially-Housed Long-Tailed Macaques (Macaca fascicularis). AB - 3,4-methylenedioxy-N-methyl amphetamine (MDMA) is one of the few known molecules to increase human and rodent prosocial behaviors. However, this effect has never been assessed on the social behavior of non-human primates. In our study, we subcutaneously injected three different doses of MDMA (1.0, 1.5 or 2.0mg/kg) to a group of three, socially housed, young male long-tailed macaques. More than 200 hours of behavioral data were recorded, during 68 behavioral sessions, by an automatic color-based video device that tracked the 3D positions of each animal and of a toy. This data was then categorized into 5 exclusive behaviors (resting, locomotion, foraging, social contact and object play). In addition, received and given social grooming was manually scored. Results show several significant dose dependent behavioral effects. At 1.5mg/kg only, MDMA induces a significant increase in social grooming behavior, thus confirming the prosocial effect of MDMA in macaques. Additionally, at 1.5 and 2.0 mg/kg MDMA injection substantially decreases foraging behavior, which is consistent with the known anorexigenic effect of this compound. Furthermore, at 2.0 mg/kg MDMA injection induces an increase in locomotor behavior, which is also in accordance with its known stimulant property. Interestingly, MDMA injected at 1.0mg/kg increases the rate of object play, which might be interpreted as a decrease of the inhibition to manipulate a unique object in presence of others, or, as an increase of the intrinsic motivation to manipulate this object. Together, our results support the effectiveness of MDMA to study the complex neurobiology of primates' social behaviors. PMID- 26840066 TI - Observation-Based Assessment of PBDE Loads in Arctic Ocean Waters. AB - Little is known about the distribution of polybrominated diphenyl ethers (PBDE) also known as flame retardants- in major ocean compartments, with no reports yet for the large deep-water masses of the Arctic Ocean. Here, PBDE concentrations, congener patterns and inventories are presented for the different water masses of the pan-Arctic shelf seas and the interior basin. Seawater samples were collected onboard three cross-basin oceanographic campaigns in 2001, 2005, and 2008 following strict trace-clean protocols. ?14PBDE concentrations in the Polar Mixed Layer (PML; a surface water mass) range from 0.3 to 11.2 pg.L(-1), with higher concentrations in the pan-Arctic shelf seas and lower levels in the interior basin. BDE-209 is the dominant congener in most of the pan-Arctic areas except for the ones close to North America, where penta-BDE and tetra-BDE congeners predominate. In deep-water masses, ?14PBDE concentrations are up to 1 order of magnitude higher than in the PML. Whereas BDE-209 decreases with depth, the less brominated congeners, particularly BDE-47 and BDE-99, increase down through the water column. Likewise, concentrations of BDE-71 -a congener not present in any PBDE commercial mixture- increase with depth, which potentially is the result of debromination of BDE-209. The inventories in the three water masses of the Central Arctic Basin (PML, intermediate Atlantic Water Layer, and the Arctic Deep Water Layer) are 158 +/- 77 kg, 6320 +/- 235 kg and 30800 +/- 3100 kg, respectively. The total load of PBDEs in the entire Arctic Ocean shows that only a minor fraction of PBDEs emissions are transported to the Arctic Ocean. These findings represent the first PBDE data in the deep-water compartments of an ocean. PMID- 26840067 TI - Clinical Application of the Food Insulin Index for Mealtime Insulin Dosing in Adults with Type 1 Diabetes: A Randomized Controlled Trial. AB - BACKGROUND: The Food Insulin Index (FII) is a novel algorithm for ranking foods based on their insulin demand relative to an isoenergetic reference food. We compared the effect of carbohydrate counting (CC) versus the FII algorithm for estimating insulin dosage on glycemic control in type 1 diabetes. MATERIALS AND METHODS: In a randomized, controlled trial, adults (n = 26) using insulin pump therapy were assigned to using either traditional CC or the novel Food Insulin Demand (FID) counting for 12 weeks. Subjects participated in group education and individual sessions. At baseline and on completion of the trial, glycated hemoglobin A1c (HbA1c), day-long glycemia (6-day continuous glucose monitoring), fasting lipids, and C-reactive protein were determined. RESULTS: Changes in HbA1c from baseline to 12 weeks were small and not significant in both groups (mean +/- SEM; FII vs. CC, -0.1 +/- 0.1% vs. -0.3 +/- 0.2%; P = 0.855). The incremental area under the curve following breakfast declined significantly among the FID counters with no change in the CC group (FID vs. CC, -93 +/- 41 mmol/L/min [P = 0.043] vs. 4 +/- 50 mmol/L/min [P = 0.938]; between groups, P = 0.143). The mean amplitude of the glycemic excursion (MAGE) was significantly reduced among the FID counters (FID vs. CC, -6.1 +/- 1.0 vs. -1.3 +/- 1.0 mmol/L; P = 0.003), and only the FID counters experienced a trend (-44% vs. +11%; P = 0.057) to reduced hypoglycemia. CONCLUSIONS: In a 12-week pilot study, MAGE and postprandial glycemia following breakfast were significantly improved with FII counting versus CC, despite no significant differences in HbA1c. PMID- 26840068 TI - Retinoic Acid Specifically Enhances Embryonic Stem Cell Metastate Marked by Zscan4. AB - Pluripotency confers Embryonic Stem Cells (ESCs) the ability to differentiate in ectoderm, endoderm, and mesoderm derivatives, producing the majority of cell types. Although the majority of ESCs divide without losing pluripotency, it has become evident that ESCs culture consists of multiple cell populations with different degrees of potency that are spontaneously induced in regular ESC culture conditions. Zscan4, a key pluripotency factor, marks ESC subpopulation that is referred to as high-level of pluripotency metastate. Here, we report that in ESC cultures treated with retinoic acid (RA), Zscan4 ESCs metastate is strongly enhanced. In particular, we found that induction of Zscan4 metastate is mediated via RA receptors (RAR-alpha, RAR-beta, and RAR-gamma), and it is dependent on phosphoinositide-3-kinase (PI3K) signaling. Remarkably, Zscan4 metastate induced by RA lacks canonical pluripotency genes Oct3/4 and Nanog but retained both self-renewal and pluripotency capabilities. Finally we demonstrated that the conditional ablation of Zscan4 subpopulation is dispensable for both endoderm and mesoderm but is required for ectoderm lineage. In conclusion, our research provides new insights about the role of RA signaling during ESCs high pluripotency metastate fluctuation. PMID- 26840069 TI - Transplantation of Immortalized CD34+ and CD34- Adipose-Derived Stem Cells Improve Cardiac Function and Mitigate Systemic Pro-Inflammatory Responses. AB - Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34- mouse ADSC lines (mADSCshTERT) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34- mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI) to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34- mADSCshTERT demonstrated phenotypic characteristics and multi differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34- mADSCshTERT, whereas CD34- mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34- mADSCshTERT primarily secreted EGF, TGF-beta1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34- mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34- mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34- mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34- mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34- mADSCshTERT into endothelial cells was found in the infarcted myocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34- mADSCshTERT groups compared to the AMI-induced control group. Transplantation of CD34- mADSCshTERT significantly reduced circulating MCP-1 levels compared to the AMI control and CD34+ mADSCshTERT groups. GFP-tagged CD34+ and CD34- mADSCshTERT are valuable resources for cell differentiation studies in vitro as well as for regeneration therapy in vivo. PMID- 26840070 TI - Alteration in Expression and Methylation of IGF2/H19 in Placenta and Umbilical Cord Blood Are Associated with Macrosomia Exposed to Intrauterine Hyperglycemia. AB - OBJECTIVE: Macrosomia is one of the most common complications in gestational diabetes mellitus. Insulin-like growth factor 2 and H19 are two of the imprinted candidate genes that are involved in fetal growth and development. Change in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 has been proved to be an early event related to the programming of metabolic profile, including macrosomia and small for gestational age in offspring. Here we hypothesize that alteration in methylation at differentially methylated region of the insulin-like growth factor 2 and H19 is associated with macrosomia induced by intrauterine hyperglycemia. RESULTS: The expression of insulin-like growth factor 2 is significant higher in gestational diabetes mellitus group (GDM group) compared to normal glucose tolerance group (NGT group) both in umbilical cord blood and placenta, while the expression of H19 is significant lower in GDM group in umbilical cord blood. The expression of insulin like growth factor 2 is significant higher in normal glucose tolerance with macrosomia group (NGT-M) compared to normal glucose tolerance with normal birthweight group (NGT-NBW group) both in placenta and umbilical cord blood. A model with interaction term of gene expression of IGF2 and H19 found that IGF2 and the joint action of IGF2 and H19 in placenta showed significantly relationship with GDM/NGT and GDM-NBW/NGT-NBW. A borderline significant association was seen among IGF2 and H19 in cord blood and GDM-M/NGT-M. The methylation level at different CpG sites of insulin-like growth factor 2 and H19 in umbilical cord blood was also significantly different among groups. Based on the multivariable linear regression analysis, the methylation of the insulin-like growth factor 2 / H19 is closely related to birth weight and intrauterine hyperglycemia. CONCLUSIONS: We confirmed the existence of alteration in DNA methylation in umbilical cord blood exposed to intrauterine hyperglycemia and reported a functional role in regulating gene associated with insulin-like growth factor 2/H19. Both of these might be the underlying pathogenesis of macrosomia. We also provided the evidence of strong associations between methylation of insulin-like growth factor 2/H19 and macrosomia induced by intrauterine hyperglycemia. PMID- 26840072 TI - A Cross Modal Performance-Based Measure of Sensory Stimuli Intricacy. AB - We define a new measure of sensory stimuli which has the following properties: It is cross modal, performance based, robust, and well defined. We interpret this measure as the intricacy or complexity of the stimuli, yet its validity is independent of its interpretation. We tested the validity and cross modality of our measure using three olfactory and one visual experiment. In order to test the link between our measure and cognitive performance we also conducted an additional visual experiment. We found that our measure is correlated with the results of the well-established Rapid Serial Visual Presentation masking experiment. Specifically, ranking stimuli according to our measure was correlated at r = 0.75 (p < 0.002) with masking effectiveness. Thus, our novel measure of sensory stimuli provides a new quantitative tool for the study of sensory processing. PMID- 26840073 TI - Retinal Oximetry with Scanning Laser Ophthalmoscope in Infants. AB - PURPOSE: Dual wavelength retinal oximetry has been developed for adults, but is not available for infants. Retinal oximetry may provide insight into the pathophysiology of oxygen-mediated diseases like retinopathy of prematurity. More insight in the oxygen metabolism of the retina in infants may provide valuable clues for better understanding and subsequent prevention or treatment of the disease. The measurements of oxygen saturation are obtained with two fundus images simultaneously captured in two different wavelengths of light. The comparison in light absorption of oxygenated and deoxygenated hemoglobin can be used to estimate the oxygen saturation within the retinal vessels by means of a software algorithm. This study aims to make retinal oximetry available for neonates. The first step towards estimating retinal oxygen saturation is determining the optical density ratio. Therefore, the purpose of this study is to image healthy newborn infants with a scanning laser ophthalmoscope and determine the optical density ratio for retinal oximetry analysis. METHODS: Images of the retina of full-term healthy infants were obtained with an SLO, Optomap 200Tx (Optos), with two laser wavelengths (532nm and 633nm). The infant lay face down on the lower arm of the parent, while the parent supported the chest and chin with one hand, and stabilized the back with the other hand. No mydriatics or eyelid specula were used during this study. The images were analyzed with modified Oxymap Analyzer software for calculation of the Optical Density Ratio (ODR) and vessel width. The ODR is inversely and approximately linearly related to the oxygen saturation. Measurements were included from the superotemporal vessel pair. A paired t-test was used for statistical analysis. RESULTS: Fifty nine infants, (58% female), were included with mean gestational age of 40 +/- 1.3 weeks (mean +/- SD) and mean post-natal age of 16 +/- 4.8 days. A total of 28 images were selected for retinal oximetry analysis. The ODR was 0.256 +/- 0.041 for the arterioles and 0.421 +/- 0.089 for the venules (n = 28, p < 0.001). The measured vessel-width for the arterioles was 14.1 +/- 2.7 pixels and for the venules 19.7 +/- 3.7 pixels (n = 28, p < 0.001). CONCLUSIONS: Retinal oximetry can be performed in newborn infants by combining an SLO and a dual-wavelength algorithm software. Sensitivity of the approach is indicated by the fact that the ODR measurements are significantly different between the arterioles and the venules. However, more variability in ODR is seen with the SLO approach in babies than is seen with conventional oximetry in adults. This approach is completely non-invasive, non-contact and even avoids the use of mydriatics or eyelid specula. PMID- 26840071 TI - Reduced Theta-Band Power and Phase Synchrony during Explicit Verbal Memory Tasks in Female, Non-Clinical Individuals with Schizotypal Traits. AB - The study of non-clinical individuals with schizotypal traits has been considered to provide a promising endophenotypic approach to understanding schizophrenia, because schizophrenia is highly heterogeneous, and a number of confounding factors may affect neuropsychological performance. Here, we investigated whether deficits in explicit verbal memory in individuals with schizotypal traits are associated with abnormalities in the local and inter-regional synchrony of brain activity. Memory deficits have been recognized as a core problem in schizophrenia, and previous studies have consistently shown explicit verbal memory impairment in schizophrenic patients. However, the mechanism of this impairment has not been fully revealed. Seventeen individuals with schizotypal traits and 17 age-matched, normal controls participated. Multichannel event related electroencephalograms (EEGs) were recorded while the subjects performed a continuous recognition task. Event-related spectral perturbations (ERSPs) and inter-regional theta-band phase locking values (TPLVs) were investigated to determine the differences in local and global neural synchrony between the two subject groups. Additionally, the connection patterns of the TPLVs were quantitatively analyzed using graph theory measures. An old/new effect was found in the induced theta-band ERSP in both groups. However, the difference between the old and new was larger in normal controls than in schizotypal trait group. The tendency of elevated old/new effect in normal controls was observed in anterior-posterior theta-band phase synchrony as well. Our results suggest that explicit memory deficits observed in schizophrenia patients can also be found in non-clinical individuals with psychometrically defined schizotypal traits. PMID- 26840074 TI - Direct Visualization of Mucus Production by the Cold-Water Coral Lophelia pertusa with Digital Holographic Microscopy. AB - Lophelia pertusa is the dominant reef-building organism of cold-water coral reefs, and is known to produce significant amounts of mucus, which could involve an important metabolic cost. Mucus is involved in particle removal and feeding processes, yet the triggers and dynamics of mucus production are currently still poorly described because the existing tools to study these processes are not appropriate. Using a novel microscopic technique-digital holographic microscopy (DHM)-we studied the mucus release of L. pertusa under various experimental conditions. DHM technology permits MUm-scale observations and allows the visualization of transparent mucoid substances in real time without staining. Fragments of L. pertusa were first maintained in flow-through chambers without stressors and imaged with DHM, then exposed to various stressors (suspended particles, particulate food and air exposure) and re-imaged. Under non-stressed conditions no release of mucus was observed, whilst mucus strings and sheaths were produced in response to suspended particles (activated charcoal and drill cuttings sediment) i.e. in a stressed condition. Mucus strings and so-called 'string balls' were also observed in response to exposure to particulate food (brine shrimp Artemia salina). Upon air-exposure, mucus production was clearly visible once the fragments were returned to the flow chamber. Distinct optical properties such as optical path length difference (OPD) were measured with DHM in response to the various stimuli suggesting that different mucus types are produced by L. pertusa. Mucus produced to reject particles is similar in refractive index to the surrounding seawater, suggesting that the energy content of this mucus is low. In contrast, mucus produced in response to either food particle addition or air exposure had a higher refractive index, suggesting a higher metabolic investment in the production of these mucoid substances. This paper shows for the first time the potential of DHM technology for the detection, characterization and quantification of mucus production through OPD measurements in L. pertusa. PMID- 26840076 TI - Periconceptional Heat Stress of Holstein Dams Is Associated with Differences in Daughter Milk Production during Their First Lactation. AB - The fertility of lactating Holstein cows is severely reduced during periods of heat stress. Despite this reduction in fertility, however, some inseminations conducted during heat stress result in successful pregnancies from which heifer calves are born. Many of these heifer calves are retained and raised to enter the milking herd as replacement animals. Heat stress experienced by these females around the time they were conceived may confer long-lasting effects that alter subsequent milk production capacity. The objective of this study was to examine the relationship between periconceptional heat stress and subsequent milk production of primiparous cows. National Dairy Herd Improvement Association data was obtained from Dairy Records Management Systems. Records included Holstein cows that had completed at least one lactation in one of three states with large populations of dairy cattle and which are known for having hot, humid summers: Georgia, Florida or Texas. Dates of conception were calculated by subtracting 276 d from the recorded birth date of each individual cow. Records for cows conceived within the months of June, July, and August were retained as heat stress conceived (HSC) cows (n = 94,440); cows conceived within the months of December, January, and February were retained as thermoneutral-conceived (TNC) contemporaries (n = 141,365). In order to account for the effects of environmental conditions on total milk production for a given lactation, cows were blocked by season of calving (winter, spring, summer or fall). Adjusted 305 day mature-equivalent milk production was evaluated with a mixed model ANOVA using SAS, in which random effects were used to account for variability between herds. Of the cows that calved in the summer, fall and winter, TNC cows had higher milk yield than the HSC cows in all states. Interestingly, the cows that calved in the spring presented a unique relationship, with HSC cows producing more milk. Overall however, heat stress at the time of conception is associated with lower milk production during the first lactation. While this association does not prove cause and effect, it does provide justification for additional investigation into whether heat stress around the time of conception results in long-term, detrimental consequences for the conceptus. PMID- 26840077 TI - The Complex Dance of the Two Conformers of Bis(trifluoromethanesulfonyl)imide as a Function of Pressure and Temperature. AB - Absorbance spectra of two ionic liquids, the short alkyl chain N-trimethyl-N propylammonium bis(trifluoromethanesulfonyl)imide (TMPA-TFSI) and the longer chain N-trimethyl-N-hexylammonium bis(trifluoromethanesulfonyl)imide (TMHA-TFSI) are reported as a function of pressure and temperature. The occurrence of various phase transitions is evidenced by the changes in the relative concentration of the cisoid and transoid conformers of their common TFSI anion. The infrared spectrum of TMPA-TFSI was measured at 300 K with an applied pressure varying over the 0-5 GPa range. Above 0.2 GPa only the trans conformer is detected, suggesting the occurrence of a pressure induced crystallization. When pressure is applied to TMHA-TFSI at T = 310 K, both TFSI conformers subsist up to ~11 GPa. However, the clear change of their intensity ratio observed around 2 GPa, suggests the onset of a glass phase as supported by measurements carried out at 4.2 GPa along a cooling/heating cycle. A careful analysis of the spectra collected along different p-T thermodynamic paths shows the occurrence of a cold crystallization at 295 K on heating from 139 K along the p = 0.5 GPa isobar. The rich phase diagrams of the two ionic liquids is the result of the competition among the anion-cation intermolecular interactions, the lower energy of trans-TFSI with respect to cis-TFSI and the smaller volume of cis-TFSI with respect to trans TFSI. PMID- 26840075 TI - Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension. AB - Pulmonary arterial hypertension (PAH) is characterized by progressive increases in vascular resistance and the remodeling of pulmonary arteries. The accumulation of inflammatory cells in the lung and elevated levels of inflammatory cytokines in the bloodstream suggest that inflammation may play a role in PAH. In this study, the benefits of induced pluripotent stem cells (iPSCs) and iPSC conditioned medium (iPSC CM) were explored in monocrotaline (MCT)-induced PAH rats. We demonstrated that both iPSCs and iPSC CM significantly reduced the right ventricular systolic pressure and ameliorated the hypertrophy of the right ventricle in MCT-induced PAH rats in models of both disease prevention and disease reversal. In the prevention of MCT-induced PAH, iPSC-based therapy led to the decreased accumulation of inflammatory cells and down-regulated the expression of the IL-1beta, IL-6, IL-12alpha, IL-12beta, IL-23 and IFNgamma genes in lung specimens, which implied that iPSC-based therapy may be involved in the regulation of inflammation. NF-kappaB signaling is essential to the inflammatory cascade, which is activated via the phosphorylation of the NF-kappaB molecule. Using the chemical inhibitor specifically blocked the phosphorylation of NF kappaB, and in vitro assays of cultured human M1 macrophages implied that the anti-inflammation effect of iPSC-based therapy may contribute to the disturbance of NF-kappaB activation. Here, we showed that iPSC-based therapy could restore the hemodynamic function of right ventricle with benefits for preventing the ongoing inflammation in the lungs of MCT-induced PAH rats by regulating NF-kappaB phosphorylation. PMID- 26840078 TI - Gardner Fibroma: Clinical and Histopathologic Implications of Germline APC Mutation Association. AB - The proportion and clinical characteristics of Gardner fibromas (GAFs) that are sporadic versus familial adenomatous polyposis (FAP)-associated have not been clearly established. We report on 7 patients diagnosed with GAF who underwent APC sequencing and duplication/deletion testing. Three (43%) were found to have underlying APC germline perturbations consistent with FAP; these patients had multifocal (1) or large; unresectable (2) GAFs. The 4 patients with negative APC testing each had a single resectable GAF. beta-catenin reactivity was noted in all FAP-associated GAFs and in 1/4 APC wild-type cases. FAP-associated GAFs may be less common than sporadic GAFs and can demonstrate clinically distinct features. PMID- 26840080 TI - Discordant Transient Extreme Hyperleukocytosis in Dichorionic Diamniotic Twins: The Role of the Sex? AB - Although a leukemoid reaction is a well-recognized phenomenon in the neonatal intensive care unit, transient extreme hyperleukocytosis in premature infants is rare. The exact mechanism is still unclear and several hypotheses are documented in the literature. In this case report, we describe 2 dichorionic diamniotic premature twins, of whom the 2 girls had extreme hyperleukocytosis, whereas their siblings did not, emphasizing the potentially important role of the sex in this phenomena. PMID- 26840079 TI - A Polymorphism in the FGFR4 Gene Is Associated With Risk of Neuroblastoma and Altered Receptor Degradation. AB - BACKGROUND: Outcomes for children with high-risk neuroblastoma are poor, and improved understanding of the mechanisms underlying neuroblastoma pathogenesis, recurrence, and treatment resistance will lead to improved outcomes. Aberrant growth factor receptor expression and receptor tyrosine kinase signaling are associated with the pathogenesis of many malignancies. A germline polymorphism in the FGFR4 gene is associated with increased receptor expression and activity and with decreased survival, treatment resistance, and aggressive disease for many malignancies. We therefore investigated the role of this FGFR4 polymorphism in neuroblastoma pathogenesis. MATERIALS AND METHODS: Germline DNA from neuroblastoma patients and matched controls was assessed for the FGFR4 Gly/Arg388 polymorphism by RT-PCR. Allele frequencies were assessed for association with neuroblastoma patient outcomes and prognostic features. Degradation rates of the FGFR4 Arg388 and Gly388 receptors and rates of receptor internalization into the late endosomal compartment were measured. RESULTS: Frequency of the FGFR4 AA genotype and the prevalence of the A allele were significantly higher in patients with neuroblastoma than in matched controls. The Arg388 receptor demonstrated slower degradation than the Gly388 receptor in neuroblastoma cells and reduced internalization into multivesicular bodies. CONCLUSIONS: The FGFR4 Arg388 polymorphism is associated with an increased prevalence of neuroblastoma in children, and this association may be linked to differences in FGFR4 degradation rates. Our study provides the first evidence of a role for FGFR4 in neuroblastoma, suggesting that FGFR4 genotype and the pathways regulating FGFR4 trafficking and degradation may be relevant for neuroblastoma pathogenesis. PMID- 26840081 TI - Disease Recurrence After Early Discontinuation of Eculizumab in a Patient With Atypical Hemolytic Uremic Syndrome With Complement C3 I1157T Mutation. AB - Eculizumab, terminal complement inhibitor, has become the frontline treatment for atypical hemolytic uremic syndrome (aHUS). However, the optimal treatment schedule has not yet been established. We describe here an aHUS patient with a mutation of C3 I1157T who achieved remission with eculizumab and suffered a recurrence after eculizumab discontinuation, a clinical situation that has not been previously described in patients with C3 mutation. A 9-year-old male experienced an onset of aHUS after viral gastroenteritis and was treated with hemodialysis. At 13 years of age he developed bacterial enterocolitis due to Campylobacter jejuni and experienced a recurrence of aHUS. Eculizumab was initiated on day 4 after disease onset resulting in recovering laboratory parameters. The patient received eculizumab for 5 months before its discontinuation. Second relapse induced by bacterial pharyngitis was confirmed 4 months after eculizumab discontinuation and prompt eculizumab reinitiation resulted in rapid remission. The patients carrying mutations in CFH or C3 have a high frequency of relapse and worse prognosis. More than 50% of aHUS relapses occurred during the first year after the onset. Therefore, long-term treatment with eculizumab is appropriate in patients with aHUS who have experienced a relapse or have mutations associated with poor prognosis. PMID- 26840082 TI - Antibody targeting facilitates effective intratumoral siRNA nanoparticle delivery to HER2-overexpressing cancer cells. AB - The therapeutic potential of RNA interference (RNAi) has been limited by inefficient delivery of short interfering RNA (siRNA). Tumor-specific recognition can be effectively achieved by antibodies directed against highly expressed cancer cell surface receptors. We investigated the utility of linking an internalizing streptavidin-conjugated HER2 antibody to an endosome-disruptive biotinylated polymeric nanocarrier to improve the functional cytoplasmic delivery of siRNA in breast and ovarian cancer cells in vitro and in an intraperitoneal ovarian cancer xenograft model in vivo, yielding an 80% reduction of target mRNA and protein levels with sustained repression for at least 96 hours. RNAi-mediated site specific cleavage of target mRNA was demonstrated using the 5' RLM-RACE (RNA ligase mediated-rapid amplification of cDNA ends) assay. Mice bearing intraperitoneal human ovarian tumor xenografts demonstrated increased tumor accumulation of Cy5.5 fluorescently labeled siRNA and 70% target gene suppression after treatment with HER2 antibody-directed siRNA nanocarriers. Detection of the expected mRNA cleavage product by 5' RLM-RACE assay confirmed that suppression occurs via the expected RNAi pathway. Delivery of siRNA via antibody-directed endosomolytic nanoparticles may be a promising strategy for cancer therapy. PMID- 26840083 TI - Long non-coding RNA LINC01133 represses KLF2, P21 and E-cadherin transcription through binding with EZH2, LSD1 in non small cell lung cancer. AB - Long non-coding RNAs are emerging as crucial regulators and prognostic markers in multiple cancers including non small cell lung cancer (NSCLC). In this study, we screened LINCO1133 as a new candidate lncRNA which promotes NSCLC development and progression, in two independent datasets (GSE18842 and GSE19804) from the Gene Expression Omnibus (GEO). LINC01133 is previously found to be over-expressed in lung squamous cell cancer (LSCC) and knockdown its expression inhibits LSCC cells invasion. However, its' molecular mechanism and downstream targets involving in regulation of cancer cells phenotype is not known. Here, we found that LINC01133 expression is up-regulated in NSCLC tissues, and its' over-expression is associated with patients poor prognosis and short survival time. LINC01133 knockdown decreased NSCLC cells proliferation, migration, invasion and induced cell cycle G1/S phase arrest and cell apoptosis. Mechanistic investigations showed that LINC01133 could interact with EZH2, LSD1 and recruit them to KLF2, P21 or E-cadherin promoter regions to repress their transcription. Furthermore, rescue experiments demonstrated that LINC01133 oncogenic function is partly through regulating KLF2. Lastly, we found that there was negative correlation between LINC01133 and KLF2, P21 or E-cadherin in NSCLC. Overall, our findings illuminate how LINC01133 over-expression confers an oncogenic function in NSCLC that may offer a novel therapy target in this disease. PMID- 26840084 TI - Irsogladine maleate, a gastric mucosal protectant, suppresses intestinal polyp development in Apc-mutant mice. AB - This study aimed to identify gastric mucosal protectants that suppress intestinal tumorigenesis in a mouse model. We chose six gastric mucosal protectants (ecabet sodium hydrate, irsogladine maleate, rebamipide, sofalcone, teprenone and troxipide) and examined their effects on the activity of oxidative stress-related transcriptional factors, including AP-1, NF-jB, NRF2, p53 and STAT3, in Caco-2 cells using a luciferase reporter gene assay. Among the six protectants, irsogladine maleate clearly inhibited NF-jB and AP-1 transcriptional activity. Furthermore, the chemopreventive property of irsogladine maleate was examined in a Min mouse model of familial adenomatous polyposis. Treatment with irsogladine maleate at doses of 5 and 50 ppm significantly reduced the number of intestinal polyps to 69% and 66% of the untreated control value, respectively. In these polyps, mRNA levels of the downstream targets of NF-jB, such as IL-1beta and IL 6, were decreased by irsogladine maleate treatment. Moreover, the levels of oxidative stress-related markers, reactive carbonyl species, in the livers of Min mice were clearly decreased following the administration of irsogladine maleate. This study demonstrated that irsogladine maleate suppresses intestinal polyp formation in Min mice partly through the NF-jB signaling pathway, thus reducing oxidative stress. PMID- 26840087 TI - Blastic plasmacytoid dendritic cell neoplasm frequently shows occult central nervous system involvement at diagnosis and benefits from intrathecal therapy. AB - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare aggressive myeloid neoplasm which shows a high rate of central nervous system (CNS) recurrence and overall survival (OS) of <1 year. Despite this, screening for CNS involvement is not routinely performed at diagnosis and intrathecal (IT) prophylaxis is not regularly administered in BPDCN. Here, we prospectively evaluated 13 consecutive BPDCN patients for the presence of CNS involvement by flow cytometry. Despite none of the patients presented with neurological symptoms, occult CNS involvement was detected in 6/10 cases evaluated at diagnosis and 3/3 studied at relapse/progression. BPDCN patients evaluated at diagnosis received IT treatment either CNS prophylaxis (n = 4) or active therapy (n = 6)- and all but one remain alive (median follow-up of 20 months). In contrast, all three patients assessed at relapse/progression died. The potential benefit of IT treatment administered early at diagnosis on OS and CNS recurrence-free survival of BPDCN was further confirmed in a retrospective cohort of another 23 BPDCN patients. Our results show that BPDCN patients studied at diagnosis frequently display occult CNS involvement; moreover, they also indicate that treatment of occult CNS disease might lead to a dramatically improved outcome of BPDCN. PMID- 26840086 TI - A function-blocking CD47 antibody suppresses stem cell and EGF signaling in triple-negative breast cancer. AB - CD47 is a signaling receptor for thrombospondin-1 and the counter-receptor for signal-regulatory protein-alpha (SIRPalpha). By inducing inhibitory SIRPalpha signaling, elevated CD47 expression by some cancers prevents macrophage phagocytosis. The anti-human CD47 antibody B6H12 inhibits tumor growth in several xenograft models, presumably by preventing SIRPalpha engagement. However, CD47 signaling in nontransformed and some malignant cells regulates self-renewal, suggesting that CD47 antibodies may therapeutically target cancer stem cells (CSCs). Treatment of MDA-MB-231 breast CSCs with B6H12 decreased proliferation and asymmetric cell division. Similar effects were observed in T47D CSCs but not in MCF7 breast carcinoma or MCF10A breast epithelial cells. Gene expression analysis in breast CSCs treated with B6H12 showed decreased expression of epidermal growth factor receptor (EGFR) and the stem cell transcription factor KLF4. EGFR and KLF4 mRNAs are known targets of microRNA-7, and B6H12 treatment correspondingly enhanced microRNA-7 expression in breast CSCs. B6H12 treatment also acutely inhibited EGF-induced EGFR tyrosine phosphorylation. Expression of B6H12-responsive genes correlated with CD47 mRNA expression in human breast cancers, suggesting that the CD47 signaling pathways identified in breast CSCs are functional in vivo. These data reveal a novel SIRPalpha-independent mechanism by which therapeutic CD47 antibodies could control tumor growth by autonomously forcing differentiation of CSC. PMID- 26840085 TI - Dual mTORC1/2 inhibition induces anti-proliferative effect in NF1-associated plexiform neurofibroma and malignant peripheral nerve sheath tumor cells. AB - Approximately 30-50% of individuals with Neurofibromatosis type 1 develop benign peripheral nerve sheath tumors, called plexiform neurofibromas (PNFs). PNFs can undergo malignant transformation to highly metastatic malignant peripheral nerve sheath tumors (MPNSTs) in 5-10% of NF1 patients, with poor prognosis. No effective systemic therapy is currently available for unresectable tumors. In tumors, the NF1 gene deficiency leads to Ras hyperactivation causing the subsequent activation of the AKT/mTOR and Raf/MEK/ERK pathways and inducing multiple cellular responses including cell proliferation. In this study, three NF1-null MPNST-derived cell lines (90-8, 88-14 and 96-2), STS26T sporadic MPNST cell line and PNF-derived primary Schwann cells were used to test responses to AZD8055, an ATP-competitive "active-site" mTOR inhibitor. In contrast to rapamycin treatment which only partially affected mTORC1 signaling, AZD8055 induced a strong inhibition of mTORC1 and mTORC2 signaling in MPNST-derived cell lines and PNF-derived Schwann cells. AZD8055 induced full blockade of mTORC1 leading to an efficient decrease of global protein synthesis. A higher cytotoxic effect was observed with AZD8055 compared to rapamycin in the NF1-null MPNST derived cell lines with IC50 ranging from 70 to 140 nM and antiproliferative effect was confirmed in PNF-derived Schwann cells. Cell migration was impaired by AZD8055 treatment and cell cycle analysis showed a G0/G1 arrest. Combined effects of AZD8055 and PD0325901 MEK inhibitor as well as BRD4 (BromoDomain-containing protein 4) inhibitors showed a synergistic antiproliferative effect. These data suggest that NF1-associated peripheral nerve sheath tumors are an ideal target for AZD8055 as a single molecule or in combined therapies. PMID- 26840088 TI - Potential therapeutic implications of IL-6/IL-6R/gp130-targeting agents in breast cancer. AB - Interleukin-6 (IL-6) is a pleiotropic cytokine with known multiple functions in immune regulation, inflammation, and oncogenesis. Binding of IL-6 to the IL-6 receptor (IL-6R) induces homodimerization and recruitment of glycoprotein 130 (gp130), which leads to activation of downstream signaling. Emerging evidence suggests that high levels of IL-6 are correlated with poor prognosis in breast cancer patients. IL-6 appears to play a critical role in the growth and metastasis of breast cancer cells, renewal of breast cancer stem cells (BCSCs), and drug resistance of BCSCs, making anti-IL-6/IL-6R/gp130 therapies promising options for the treatment and prevention of breast cancers. However, preclinical and clinical studies of the applications of anti-IL-6/IL-6R/gp130 therapy in breast cancers are limited. In this review, we summarize the structures, preclinical and clinical studies, mechanisms of action of chemical and biological blockers that directly bind to IL-6, IL-6R, or gp130, and the potential clinical applications of these pharmacological agents as breast cancer therapies. PMID- 26840091 TI - Targeting Toll-like receptor 4 prevents cobalt-mediated inflammation. AB - Cobalt-chrome alloy is a widely used biomaterial in joint replacements, dental implants and spinal rods. Although it is an effective and biocompatible material, adverse reactions to metal debris (ARMD) have arisen in a minority of patients, particularly in those with metal-on-metal bearing hip replacements. There is currently no treatment for ARMD and once progressive, early revision surgery of the implant is necessary. Therapeutic agents to prevent, halt or reverse ARMD would therefore be advantageous. Cobalt ions activate Toll-like receptor 4 (TLR4), an innate immune receptor responsible for inflammatory responses to bacterial lipopolysaccharide (LPS) resulting in the production of pro inflammatory cytokines and chemokines. We hypothesised that anti-TLR4 neutralising antibodies, reported to inhibit TLR4-mediated inflammation, could prevent the inflammatory response to cobalt ions in an in vitro macrophage cell culture model. This study shows that a monoclonal anti-TLR4 antibody inhibited cobalt-mediated increases in pro-inflammatory IL8, CCL20 and IL1A expression, as well as IL-8 secretion. In contrast, a polyclonal antibody did not prevent the effect of cobalt ions on either IL-8 or IL1A expression, although it did have a small effect on the CCL20 response. Interestingly, both antibodies inhibited cobalt-mediated neutrophil migration although the greater effect was observed with the monoclonal antibody. In summary our data shows that a monoclonal anti TLR4 antibody can inhibit cobalt-mediated inflammatory responses while a polyclonal antibody only inhibits the effect of specific cytokines. Anti-TLR4 antibodies have therapeutic potential in ARMD although careful antibody design is required to ensure that the LPS response is preserved. PMID- 26840089 TI - Amyloid precursor protein and amyloid precursor-like protein 2 in cancer. AB - Amyloid precursor protein (APP) and its family members amyloid precursor-like protein 1 (APLP1) and amyloid precursor-like protein 2 (APLP2) are type 1 transmembrane glycoproteins that are highly conserved across species. The transcriptional regulation of APP and APLP2 is similar but not identical, and the cleavage of both proteins is regulated by phosphorylation. APP has been implicated in Alzheimer's disease causation, and in addition to its importance in neurology, APP is deregulated in cancer cells. APLP2 is likewise overexpressed in cancer cells, and APLP2 and APP are linked to increased tumor cell proliferation, migration, and invasion. In this present review, we discuss the unfolding account of these APP family members' roles in cancer progression and metastasis. PMID- 26840092 TI - Thrombopoietin: a potential diagnostic indicator of immune thrombocytopenia in pregnancy. AB - To evaluate whether the serum thrombopoietin levels in pregnancy-associated immune thrombocytopenia (ITP) differ from those in gestational thrombocytopenia, and reveal the possibility of thrombopoietin serving as a marker for differential diagnosis. Serum thrombopoietin concentration was determined in ITP in pregnancy (n = 35), gestational thrombocytopenia (n = 31), healthy pregnancy (n = 32), age matched nonpregnant ITP (n = 32) and nonpregnant healthy controls (n = 35) by ELISA. The serum thrombopoietin level of ITP in pregnancy (1283 +/- 646 pg/mL) was significantly higher than gestational thrombocytopenia (187 +/- 64 pg/mL) (P < 0.01), although the platelet counts of these two disorders may overlap. Twenty nine of 35 patients with ITP in pregnancy had thrombopoietin values >500 pg/mL, whereas none of the gestational thrombocytopenia patients' thrombopoietin levels exceeded 500 pg/mL. In addition, ITP in pregnancy presented a markedly higher thrombopoietin level than nonpregnant ITP (88 +/- 41 pg/mL) (P < 0.01), indicating that the pathogenesis of pregnant and nonpregnant ITP was different. Our findings suggest that measurement of serum thrombopoietin concentration provides valuable diagnostic information for differentiating ITP in pregnancy from gestational thrombocytopenia. Thrombopoietin represents a reliable marker for ITP in pregnancy. PMID- 26840090 TI - CRISPR/Cas9 and cancer targets: future possibilities and present challenges. AB - All cancers have multiple mutations that can largely be grouped into certain classes depending on the function of the gene in which they lie and these include oncogenic changes that enhance cellular proliferation, loss of function of tumor suppressors that regulate cell growth potential and induction of metabolic enzymes that confer resistance to chemotherapeutic agents. Thus the ability to correct such mutations is an important goal in cancer treatment. Recent research has led to the developments of reagents which specifically target nucleotide sequences within the cellular genome and these have a huge potential for expanding our anticancer armamentarium. One such a reagent is the clustered regulatory interspaced short palindromic repeat (CRISPR)-associated 9 (Cas9) system, a powerful, highly specific and adaptable tool that provides unparalleled control for editing the cellular genome. In this short review, we discuss the potential of CRISPR/Cas9 against human cancers and the current difficulties in translating this for novel therapeutic approaches. PMID- 26840094 TI - Standard Biocompatibility Studies Do Not Predict All Effects of PVA/CMC Anti Adhesive Gel in vivo. AB - PURPOSE: PVA/CMC (polyvinyl alcohol/carboxymethyl cellulose) hydrogel fulfills various physiochemical properties required for an adhesion barrier and has shown good anti-adhesion properties in previous in vivo studies. In this investigation, we assessed the in vitro and in vivo biocompatibility of PVA/CMC gel and compared this to the functionality and promotion of wound healing for two surgical indications. METHODS: Standardized ISO10993 in vitro and in vivo biocompatibility studies, comprising cytotoxicity, genotoxicity, acute systemic toxicity, delayed contact and maximization sensitization test, intracutaneous reactivity and local muscle implantation, were performed on PVA/CMC gel. In the functional studies, PVA/CMC gel was applied - on the one hand - to a rabbit abdominal wall model enforced with a polypropylene mesh for testing the anti-adhesion properties and - on the other hand - to an end- to-end anastomosis model that was selected for surveying potential influences of different dosages of PVA/CMC gel on anastomotic wound healing. RESULTS: The ISO10993 methods indicated generally good biocompatibility properties, such as the absence of cytotoxic and mutagenic effects as well as no signs of systemic toxicity and sensitization potentials. No irritation effects were observed after the intracutaneous injection of lipophilic PVA/CMC sesame oil extract. However, the injection of hydrophilic PVA/CMC physiologic saline extract induced slight irritation. Following rabbit muscle implantation of the PVA membrane for 2, 4, 12, 26 and 52 weeks, a slight irritant effect was observed at 12 weeks due to the peak of phagocytosis. In the functionality tests, PVA/CMC gel showed good anti-adhesive effects in the abdominal wall model enforced with the mesh, with significantly lower and less tense adhesions compared to the untreated control. However, moderate signs of inflammation, especially in the spleen were observed after the intra-abdominal implantation of 3.3 ml PVA/CMC gel per kg body weight. In the end-to-end anastomosis model, PVA/CMC gel had no influence on wound healing. For dosages of 1-6 ml gel per treatment, no signs of intestinal leaks were detected, and tensile strength was equal to that of the untreated control, but again more moderate signs of inflammation in the spleen were observed at a dosage >3 ml. CONCLUSION: Comparing the standardized ISO10993 methods, anti-adhesive PVA/CMC gel displays good biocompatibility. However, those methods do not seem to be sensitive enough because the rabbit abdominal wall and the end-to-end anastomosis models display more effects with respect to the dosage and routes of the intra-abdominal resorption of PVA/CMC gel - with the recommended <2 ml PVA/CMC gel per kg body weight as a secure dosage. PMID- 26840093 TI - Marital status independently predicts gastric cancer survival after surgical resection--an analysis of the SEER database. AB - Marital status was found to be an independent prognostic factor for survival in various cancer types, but it hasn't been studied in gastric cancer. The Surveillance, Epidemiology and End Results database was used to compare survival outcomes with marital status. A total of 16,106 eligible patients were identified. Patients in the widowed group had the highest proportion of women, more common site of stomach, more prevalence of elderly patients, higher percentage of adenocarcinoma, and more tumors at localized stage (P < 0.05). Patients in married group had better 5year cause-specific survival (CSS) than those unmarried (P < 0.05). Further analysis showed that widowed patients always presented the lowest CSS compared with that of other groups. Widowed patients had 7.1% reduction in 5-year CSS compared with married patients at Localized stage (77.2% vs 70.1%, P < 0.001), 9.6% reduction at Regional stage (38.2% vs 28.6%, P < 0.001), and 4.7% reduction at Distant stage (13.3% vs 8.6%, P < 0.001). These results showed that unmarried patients were at greater risk of cancer specific mortality. Despite favorable clinicpathological characteristics, widowed patients were at highest risk of death compared with other groups. PMID- 26840095 TI - Computational Exploration of Molecular Scaffolds in Medicinal Chemistry. AB - The scaffold concept is widely applied in medicinal chemistry. Scaffolds are mostly used to represent core structures of bioactive compounds. Although the scaffold concept has limitations and is often viewed differently from a chemical and computational perspective, it has provided a basis for systematic investigations of molecular cores and building blocks, going far beyond the consideration of individual compound series. Over the past 2 decades, alternative scaffold definitions and organization schemes have been introduced and scaffolds have been studied in a variety of ways and increasingly on a large scale. Major applications of the scaffold concept include the generation of molecular hierarchies, structural classification, association of scaffolds with biological activities, and activity prediction. This contribution discusses computational approaches for scaffold generation and analysis, with emphasis on recent developments impacting medicinal chemistry. A variety of scaffold-based studies are discussed, and a perspective on scaffold methods is provided. PMID- 26840097 TI - Exploring Nonspecific Protein Adsorption on Lignocellulosic Amphiphilic Bicomponent Films. AB - In this contribution, we explore the interaction of lignocellulosics and proteins aiming at a better understanding of their synergistic role in natural systems. In particular, the manufacturing and characterization of amphiphilic bicomponent thin films composed of hydrophilic cellulose and a hydrophobic lignin ester in different ratios is presented which may act as a very simplified model for real systems. Besides detailed characterizations of the films and mechanisms to explain their formation, nonspecific protein adsorption using bovine serum albumin (BSA) onto the films was studied using a quartz crystal microbalance with dissipation (QCM-D). As it turns out, the rather low nonspecific protein adsorption of BSA on cellulose is further reduced when these hydrophobic lignins are incorporated into the films. The lignin ester acts in these blend films as sacrificial component, probably via an emulsification mechanism. Additionally, the amphiphilicity of the films may prevent the adsorption of BSA as well. Although there are some indications, it remains unclear whether any kind of protein interactions in such systems are of specific nature. PMID- 26840098 TI - An Efficient Computational Approach for the Calculation of the Vibrational Density of States. AB - We present an optimized approach for the calculation of the density of fully coupled vibrational states in high-dimensional systems. This task is of paramount importance, because partition functions and several thermodynamic properties can be accurately estimated once the density of states is known. A new code, called paradensum, based on the implementation of the Wang-Landau Monte Carlo algorithm for parallel architectures is described and applied to real complex systems. We test the accuracy of paradensum on several molecular systems, including some benchmarks for which an exact evaluation of the vibrational density of states is doable by direct counting. In addition, we find a significant computational speedup with respect to standard approaches when applying our code to molecules up to 66 degrees of freedom. The new code can easily handle 150 degrees of freedom. These features make paradensum a very promising tool for future calculations of thermodynamic properties and thermal rate constants of complex systems. PMID- 26840099 TI - Positional Asphyxia: Death Due to Unusual Head-Down Position in a Narrow Space. AB - Death due to a head-down position with hyperflexion of the neck is a rare event. A person accidentally falling into a narrow space and remaining in an upside-down position with no timely recovery may experience positional or postural asphyxia. It is a critical condition arising out of particular body positions, leading to mechanical obstruction of respiration. The precipitating factors are intoxication due to alcohol, drugs, obesity, psychiatric illnesses, and injuries. A 30-year old unmarried woman, weighing 82 kg and with a body mass index of 31.24, was found in a narrow space between the bed and the wall in a naked state and in a head-down position with hyperflexion of the neck. The distribution of lividity was consistent with the position of the body at the scene. Blood was oozing from the mouth and nostrils, and signs of asphyxia were present. The toxicological analyses of viscera, blood, and urine were negative for alcohol, drugs, and poisons. Glucose levels in the blood (86 mg/dL) as well as urine and vitreous humor levels (68 mg/dL) were within normal limits. On microscopic examination, there were no findings of coronary atherosclerosis, whereas the brain and lung were edematous. After meticulous examination, we ruled out sexual assault, autoerotic asphyxia, epilepsy, psychiatric illness, diabetes, toxicity, and coronary artery disease. Death was attributed to the accidental fall of the obese individual being stuck in a narrow space, resulting in positional asphyxia. It is imperative to recognize the precipitating or risk factors before labeling positional asphyxia as a cause of death. PMID- 26840100 TI - Precis for JCEM: No Empty Promises. PMID- 26840103 TI - Response to the Letter by Rao S.D., et al. PMID- 26840104 TI - Letter to the Editor: Ultrasound assessment of abdominal visceral adipose tissue for cardiovascular risk. PMID- 26840105 TI - Response to the Letter: Comment on "Abdominal Fat Distribution and Cardiovascular Risk in Men and Women With Different Levels of Glucose Tolerance" by Scheuer S.H., et al. PMID- 26840106 TI - Letter to the Editor: A Possible Mechanism of Denosumab Treatment for Fracture Prevention. PMID- 26840107 TI - Letter to the Editor: Comments on "Are biochemical markers of bone turnover representative of bone histomorphometry in 370 postmenopausal women?" by Chavassieux P, Portero-Muzy N, Roux JP, Garnero P, Chapurlat R. PMID- 26840108 TI - Response to the Letter by Scillitani, et al. PMID- 26840109 TI - Letter to the Editor: "Use of biomarkers to identify new drug targets and to predict risk of cardiometabolic outcomes" by Holmegard HN, et al. PMID- 26840110 TI - Response to the Letter: Response to "Use of biomarkers to identify new drug targets and to predict risk of cardiometabolic outcomes" by Abasi A., et al. PMID- 26840096 TI - Report from IPITA-TTS Opinion Leaders Meeting on the Future of beta-Cell Replacement. PMID- 26840111 TI - Letter to the Editor: Re: Are Biochemical Markers of Bone Turnover Representative of Bone Histomorphometry in 370 Postmenopausal Women? PMID- 26840112 TI - Response to the Letter: Are Biochemical Markers of Bone Turnover Representative of Bone Histomorphometry in 370 Postmenopausal Women? PMID- 26840113 TI - Letter to the Editor: Comment on "SGLT2 inhibitors may predispose to ketoacidosis" by Taylor S.I., et al. PMID- 26840114 TI - Response to the Letter: Comment to letter by Segar L. PMID- 26840115 TI - Letter to the Editor: "Transdermal vs Oral Estrogen Therapy and Venous Thromboembolism: Upgrade the Level of Evidence" by. PMID- 26840116 TI - Response to the Letter: "Transdermal vs oral estrogen therapy and venous thromboembolism: upgrade the level of evidence" by Scarabin MC, et al. PMID- 26840117 TI - Letter to the Editor: One-Hour Postload Hyperglycemia is a Stronger Predictor of Type 2 Diabetes than Impaired Fasting Glucose. PMID- 26840118 TI - Response to the Letter: Comment to the letter by Marathe CS, Rayne CK, Jones KL, Horowitz M. PMID- 26840119 TI - Letter to the Editor: Demonstration of Elevated Cerebrospinal Fluid CRH Levels During Pregnancy Provides Support for (Not Against) the Link Between CRH and Postpartum Depression. PMID- 26840120 TI - Response to Letter by Hahn-Holbrook J., et al. PMID- 26840121 TI - Letter to the Editor: Effect of Parathyroidectomy on Renal Function: Dichotomous Results and Confusing Conclusions. PMID- 26840123 TI - Photoredox Mediated Nickel Catalyzed Cross-Coupling of Thiols With Aryl and Heteroaryl Iodides via Thiyl Radicals. AB - Ni-catalyzed cross-couplings of aryl, benzyl, and alkyl thiols with aryl and heteroaryl iodides were accomplished in the presence of an Ir-photoredox catalyst. Highly chemoselective C-S cross-coupling was achieved versus competitive C-O and C-N cross-couplings. This C-S cross-coupling method exhibits remarkable functional group tolerance, and the reactions can be carried out in the presence of molecular oxygen. Mechanistic investigations indicated that the reaction proceeded through transient Ni(I)-species and thiyl radicals. Distinct from nickel-catalyzed cross-coupling reactions involving carbon-centered radicals, control experiments and spectroscopic studies suggest that this C-S cross-coupling reaction does not involve a Ni(0)-species. PMID- 26840122 TI - Short Term Survival after Admission for Heart Failure in Sweden: Applying Multilevel Analyses of Discriminatory Accuracy to Evaluate Institutional Performance. AB - BACKGROUND: Hospital performance is frequently evaluated by analyzing differences between hospital averages in some quality indicators. The results are often expressed as quality charts of hospital variance (e.g., league tables, funnel plots). However, those analyses seldom consider patients heterogeneity around averages, which is of fundamental relevance for a correct evaluation. Therefore, we apply an innovative methodology based on measures of components of variance and discriminatory accuracy to analyze 30-day mortality after hospital discharge with a diagnosis of Heart Failure (HF) in Sweden. METHODS: We analyzed 36,943 patients aged 45-80 treated in 565 wards at 71 hospitals during 2007-2009. We applied single and multilevel logistic regression analyses to calculate the odds ratios and the area under the receiver-operating characteristic (AUC). We evaluated general hospital and ward effects by quantifying the intra-class correlation coefficient (ICC) and the increment in the AUC obtained by adding random effects in a multilevel regression analysis (MLRA). Finally, the Odds Ratios (ORs) for specific ward and hospital characteristics were interpreted jointly with the proportional change in variance (PCV) and the proportion of ORs in the opposite direction (POOR). FINDINGS: Overall, the average 30-day mortality was 9%. Using only patient information on age and previous hospitalizations for different diseases we obtained an AUC = 0.727. This value was almost unchanged when adding sex, country of birth as well as hospitals and wards levels. Average mortality was higher in small wards and municipal hospitals but the POOR values were 15% and 16% respectively. CONCLUSIONS: Swedish wards and hospitals in general performed homogeneously well, resulting in a low 30-day mortality rate after HF. In our study, knowledge on a patient's previous hospitalizations was the best predictor of 30-day mortality, and this information did not improve by knowing the sex and country of birth of the patient or where the patient was treated. PMID- 26840124 TI - Coordinated Bacteriocin Expression and Competence in Streptococcus pneumoniae Contributes to Genetic Adaptation through Neighbor Predation. AB - Streptococcus pneumoniae (pneumococcus) has remained a persistent cause of invasive and mucosal disease in humans despite the widespread use of antibiotics and vaccines. The resilience of this organism is due to its capacity for adaptation through the uptake and incorporation of new genetic material from the surrounding microbial community. DNA uptake and recombination is controlled by a tightly regulated quorum sensing system that is triggered by the extracellular accumulation of competence stimulating peptide (CSP). In this study, we demonstrate that CSP can stimulate the production of a diverse array of blp bacteriocins. This cross stimulation occurs through increased production and secretion of the bacteriocin pheromone, BlpC, and requires a functional competence regulatory system. We show that a highly conserved motif in the promoter of the operon encoding BlpC and its transporter mediates the upregulation by CSP. The accumulation of BlpC following CSP stimulation results in augmented activation of the entire blp locus. Using biofilm-grown organisms as a model for competition and genetic exchange on the mucosal surface, we demonstrate that DNA exchange is enhanced by bacteriocin secretion suggesting that co-stimulation of bacteriocins with competence provides an adaptive advantage. The blp and com regulatory pathways are believed to have diverged and specialized in a remote ancestor of pneumococcus. Despite this, the two systems have maintained a regulatory connection that promotes competition and adaptation by targeting for lysis a wide array of potential competitors while simultaneously providing the means for incorporation of their DNA. PMID- 26840125 TI - Comprehensive Annotation of the Parastagonospora nodorum Reference Genome Using Next-Generation Genomics, Transcriptomics and Proteogenomics. AB - Parastagonospora nodorum, the causal agent of Septoria nodorum blotch (SNB), is an economically important pathogen of wheat (Triticum spp.), and a model for the study of necrotrophic pathology and genome evolution. The reference P. nodorum strain SN15 was the first Dothideomycete with a published genome sequence, and has been used as the basis for comparison within and between species. Here we present an updated reference genome assembly with corrections of SNP and indel errors in the underlying genome assembly from deep resequencing data as well as extensive manual annotation of gene models using transcriptomic and proteomic sources of evidence (https://github.com/robsyme/Parastagonospora_nodorum_SN15). The updated assembly and annotation includes 8,366 genes with modified protein sequence and 866 new genes. This study shows the benefits of using a wide variety of experimental methods allied to expert curation to generate a reliable set of gene models. PMID- 26840127 TI - Excitonic Lasing in Solution-Processed Subwavelength Nanosphere Assemblies. AB - Lasing in solution-processed nanomaterials has gained significant interest because of the potential for low-cost integrated photonic devices. Still, a key challenge is to utilize a comprehensive knowledge of the system's spectral and temporal dynamics to design low-threshold lasing devices. Here, we demonstrate intrinsic lasing (without external cavity) at low-threshold in an ultrathin film of coupled, highly crystalline nanospheres with overall thickness on the order of ~lambda/4. The cavity-free geometry consists of ~35 nm zinc oxide nanospheres that collectively localize the in-plane emissive light fields while minimizing scattering losses, resulting in excitonic lasing with fluence thresholds at least an order of magnitude lower than previous UV-blue random and quantum-dot lasers (<75 MUJ/cm(2)). Fluence-dependent effects, as quantified by subpicosecond transient spectroscopy, highlight the role of phonon-mediated processes in excitonic lasing. Subpicosecond evolution of distinct lasing modes, together with three-dimensional electromagnetic simulations, indicate a random lasing process, which is in violation of the commonly cited criteria of strong scattering from individual nanostructures and an optically thick sample. Subsequently, an electron-hole plasma mechanism is observed with increased fluence. These results suggest that coupled nanostructures with high crystallinity, fabricated by low cost solution-processing methods, can function as viable building blocks for high performance optoelectronics devices. PMID- 26840126 TI - A Temperature Sensitive Variant of p53 Drives p53-Dependent MicroRNA Expression without Evidence of Widespread Post-Transcriptional Gene Silencing. AB - The p53 tumour suppressor is a transcription factor that can regulate the expression of numerous genes including many encoding proteins and microRNAs (miRNAs). The predominant outcomes of a typical p53 response are the initiation of apoptotic cascades and the activation of cell cycle checkpoints. HT29-tsp53 cells express a temperature sensitive variant of p53 and in the absence of exogenous DNA damage, these cells preferentially undergo G1 phase cell cycle arrest at the permissive temperature that correlates with increased expression of the cyclin-dependent kinase inhibitor p21WAF1. Recent evidence also suggests that a variety of miRNAs can induce G1 arrest by inhibiting the expression of proteins like CDK4 and CDK6. Here we used oligonucleotide microarrays to identify p53 regulated miRNAs that are induced in these cells undergoing G1 arrest. At the permissive temperature, the expression of several miRNAs was increased through a combination of either transcriptional or post-transcriptional regulation. In particular, miR-34a-5p, miR-143-3p and miR-145-5p were strongly induced and they reached levels comparable to that of reference miRNAs (miR-191 and miR-103). Importantly, miR-34a-5p and miR-145-5p are known to silence the Cdk4 and/or Cdk6 G1 cyclin-dependent kinases (cdks). Surprisingly, there was no p53-dependent decrease in the expression of either of these G1 cdks. To search for other potential targets of p53-regulated miRNAs, p53-downregulated mRNAs were identified through parallel microarray analysis of mRNA expression. Once again, there was no clear effect of p53 on the repression of mRNAs under these conditions despite a remarkable increase in p53-induced mRNA expression. Therefore, despite a strong p53 transcriptional response, there was no clear evidence that p53-responsive miRNA contributed to gene silencing. Taken together, the changes in cell cycle distribution in this cell line at the permissive temperature is likely attributable to transcriptional upregulation of the CDKN1A mRNA and p21WAF1 protein and not to the down regulation of CDK4 or CDK6 by p53 regulated miRNAs. PMID- 26840128 TI - The Impact of a Clinical Decision Support System in Diabetes Primary Care Patients in a Developing Country. AB - BACKGROUND: Telehealth strategies have the potential to improve diabetes care, but there is a lack of evidence about the impact of these strategies in developing countries. Our objective was to analyze the feasibility, usability, and clinical impact of a decision support system (DSS) in Brazilian primary care diabetes patients. MATERIALS AND METHODS: This was a quasi-experimental study that included type 2 diabetes primary care patients >40 years of age. Patients were assessed before (during 6 months) and after the implementation of the DSS application (4 months). The DSS application, used by health professionals, included clinical evaluations and blood glucose measurements and generated specific recommendations based on the data entered. RESULTS: In total, 145 patients were included (mean age, 62.0 +/- 9.9 years), 62.1% were female, and 70.0% had been diagnosed with diabetes more than 5 years ago. Overall, there was no decrease in median hemoglobin A1c (HbA1c), from 7.7% (range, 6.5-9.8%) to 7.4% (range, 6.5-9.2%) (P for slope = 0.347). Subgroup analysis showed that patients with an HbA1c level of >=9% at baseline had a significant reduction in median HbA1c level, from 10.5% (range, 9.9-11.3%) to 10.0% (range, 8.9-10.9%) (P for difference of slope between subgroups = 0.004). The reduction occurred in the first phase of the study, before the DSS use. Healthcare practitioners considered the DSS easy to use (99%) and believed that it provided useful information for patient care (100%). CONCLUSIONS: In this study the improvement of glycemic control before the application in more decompensated patients (HbA1c >=9%) probably reflects the systematization of diabetes care. The DSS use did not improve the HbA1c level, possibly because of the short follow-up and/or infrequent use by the healthcare practitioners. PMID- 26840130 TI - Universalism, Responsiveness, Sustainability--Regulating the French Health Care System. PMID- 26840131 TI - Tolerable Risks? Physicians and Youth Tackle Football. PMID- 26840129 TI - MutAid: Sanger and NGS Based Integrated Pipeline for Mutation Identification, Validation and Annotation in Human Molecular Genetics. AB - Traditional Sanger sequencing as well as Next-Generation Sequencing have been used for the identification of disease causing mutations in human molecular research. The majority of currently available tools are developed for research and explorative purposes and often do not provide a complete, efficient, one-stop solution. As the focus of currently developed tools is mainly on NGS data analysis, no integrative solution for the analysis of Sanger data is provided and consequently a one-stop solution to analyze reads from both sequencing platforms is not available. We have therefore developed a new pipeline called MutAid to analyze and interpret raw sequencing data produced by Sanger or several NGS sequencing platforms. It performs format conversion, base calling, quality trimming, filtering, read mapping, variant calling, variant annotation and analysis of Sanger and NGS data under a single platform. It is capable of analyzing reads from multiple patients in a single run to create a list of potential disease causing base substitutions as well as insertions and deletions. MutAid has been developed for expert and non-expert users and supports four sequencing platforms including Sanger, Illumina, 454 and Ion Torrent. Furthermore, for NGS data analysis, five read mappers including BWA, TMAP, Bowtie, Bowtie2 and GSNAP and four variant callers including GATK HaplotypeCaller, SAMTOOLS, Freebayes and VarScan2 pipelines are supported. MutAid is freely available at https://sourceforge.net/projects/mutaid. PMID- 26840132 TI - Lost in Translation. PMID- 26840133 TI - Metformin versus Placebo in Obese Pregnant Women without Diabetes Mellitus. AB - BACKGROUND: Obesity is associated with an increased risk of adverse pregnancy outcomes. Lifestyle-intervention studies have not shown improved outcomes. Metformin improves insulin sensitivity and in pregnant patients with gestational diabetes it leads to less weight gain than occurs in those who do not take metformin. METHODS: In this double-blind, placebo-controlled trial, we randomly assigned pregnant women without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of more than 35 to receive metformin, at a dose of 3.0 g per day, or placebo (225 women in each group) from 12 to 18 weeks of gestation until delivery. The BMI was calculated at the time of study entry (12 to 18 weeks of gestation). The primary outcome was a reduction in the median neonatal birth-weight z score by 0.3 SD (equivalent to a 50% reduction, from 20% to 10%, in the incidence of large-for gestational-age neonates). Secondary outcomes included maternal gestational weight gain and the incidence of gestational diabetes and of preeclampsia, as well as the incidence of adverse neonatal outcomes. Randomization was performed with the use of computer-generated random numbers. The analysis was performed according to the intention-to-treat principle. RESULTS: A total of 50 women withdrew consent during the trial, which left 202 women in the metformin group and 198 in the placebo group. There was no significant between-group difference in the median neonatal birth-weight z score (0.05 in the metformin group [interquartile range, -0.71 to 0.92] and 0.17 in the placebo group [interquartile range, -0.62 to 0.89], P=0.66). The median maternal gestational weight gain was lower in the metformin group than in the placebo group (4.6 kg [interquartile range, 1.3 to 7.2] vs. 6.3 kg [interquartile range, 2.9 to 9.2], P<0.001), as was the incidence of preeclampsia (3.0% vs. 11.3%; odds ratio, 0.24; 95% confidence interval, 0.10 to 0.61; P=0.001). The incidence of side effects was higher in the metformin group than in the placebo group. There were no significant between group differences in the incidence of gestational diabetes, large-for-gestational age neonates, or adverse neonatal outcomes. CONCLUSIONS: Among women without diabetes who had a BMI of more than 35, the antenatal administration of metformin reduced maternal weight gain but not neonatal birth weight. (Funded by the Fetal Medicine Foundation; ClinicalTrials.gov number, NCT01273584; EudraCT number, 2008 005892-83.). PMID- 26840134 TI - Routine Amoxicillin for Uncomplicated Severe Acute Malnutrition in Children. AB - BACKGROUND: High-quality evidence supporting a community-based treatment protocol for children with severe acute malnutrition, including routine antibiotic use at admission to a nutritional treatment program, remains limited. In view of the costs and consequences of emerging resistance associated with routine antibiotic use, more evidence is required to support this practice. METHODS: In a double blind, placebo-controlled trial in Niger, we randomly assigned children who were 6 to 59 months of age and had uncomplicated severe acute malnutrition to receive amoxicillin or placebo for 7 days. The primary outcome was nutritional recovery at or before week 8. RESULTS: A total of 2412 children underwent randomization, and 2399 children were included in the analysis. Nutritional recovery occurred in 65.9% of children in the amoxicillin group (790 of 1199) and in 62.7% of children in the placebo group (752 of 1200). There was no significant difference in the likelihood of nutritional recovery (risk ratio for amoxicillin vs. placebo, 1.05; 95% confidence interval [CI], 0.99 to 1.12; P=0.10). In secondary analyses, amoxicillin decreased the risk of transfer to inpatient care by 14% (26.4% in the amoxicillin group vs. 30.7% in the placebo group; risk ratio, 0.86; 95% CI, 0.76 to 0.98; P=0.02). CONCLUSIONS: We found no benefit of routine antibiotic use with respect to nutritional recovery from uncomplicated severe acute malnutrition in Niger. In regions with adequate infrastructure for surveillance and management of complications, health care facilities could consider eliminating the routine use of antibiotics in protocols for the treatment of uncomplicated severe acute malnutrition. (Funded by Medecins sans Frontieres Operational Center Paris; ClinicalTrials.gov number, NCT01613547.). PMID- 26840135 TI - The Role of Risk-Reducing Surgery in Hereditary Breast and Ovarian Cancer. PMID- 26840136 TI - IMAGES IN CLINICAL MEDICINE. Katayama Fever. PMID- 26840137 TI - CLINICAL PROBLEM-SOLVING. From Dancing to Debilitated. PMID- 26840139 TI - Aspirin-Exacerbated Respiratory Disease--New Prime Suspects. PMID- 26840140 TI - Remote Ischemic Preconditioning and Cardiac Surgery. PMID- 26840141 TI - Remote Ischemic Preconditioning and Cardiac Surgery. PMID- 26840142 TI - Remote Ischemic Preconditioning and Cardiac Surgery. PMID- 26840143 TI - Remote Ischemic Preconditioning and Cardiac Surgery. PMID- 26840144 TI - Nivolumab in Nonsquamous Non-Small-Cell Lung Cancer. PMID- 26840145 TI - Nivolumab in Nonsquamous Non-Small-Cell Lung Cancer. PMID- 26840146 TI - Nivolumab in Nonsquamous Non-Small-Cell Lung Cancer. PMID- 26840147 TI - Politics and Universal Health Coverage. PMID- 26840148 TI - More on Merkel-Cell Carcinoma. PMID- 26840150 TI - Reexamining the Ecology of Medical Care. PMID- 26840149 TI - More on Merkel-Cell Carcinoma. PMID- 26840151 TI - Probable Person-to-Person Transmission of Legionnaires' Disease. PMID- 26840152 TI - IMAGES IN CLINICAL MEDICINE. Cocaine-Induced Coronary-Artery Vasospasm. PMID- 26840154 TI - The Hydroxyl Radical is a Critical Intermediate in the Voltammetric Detection of Hydrogen Peroxide. AB - Cyclic voltammetry is a widely used and powerful tool for sensitively and selectively measuring hydrogen peroxide (H2O2). Herein, voltammetry was combined with electron paramagnetic resonance spectroscopy to identify and define the role of an oxygen-centered radical liberated during the oxidation of H2O2. The spin trap reagents, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and 2-ethoxycarbonyl-2 methyl-3,4-dihydro-2H-pyrrole-1-oxide (EMPO), were employed. Spectra exhibit distinct hyperfine patterns that clearly identify the DMPO(*)-OH and EMPO(*)-OH adducts. Multiple linear regression analysis of voltammograms demonstrated that the hydroxyl radical is a principal contributor to the voltammetry of H2O2, as signal is attenuated when this species is trapped. These data incorporate a missing, fundamental element to our knowledge of the mechanisms that underlie H2O2 electrochemistry. PMID- 26840155 TI - Center Volume and Extracorporeal Membrane Oxygenation Support at Lung Transplantation in the Lung Allocation Score Era. AB - RATIONALE: Outcomes related to extracorporeal membrane oxygenation (ECMO) used to bridge patients to lung transplantation in the context of center differences in transplant expertise have not been investigated. OBJECTIVES: To determine the effects of ECMO at time of transplant on survival in adult patients who underwent transplant surgery in historically low- and high-volume centers. METHODS: The United Network for Organ Sharing database was used to classify centers according to transplant volume between May 2005 and May 2010 as low-volume centers (bottom 50% of centers), medium-volume centers (next 25%), or high-volume centers (top 25%). Influences of ECMO on post-transplant survival were estimated among adults receiving lung transplants between June 2010 and June 2015 based on historic center volume in the preceding 5 years. MEASUREMENTS AND MAIN RESULTS: Sixty-five centers were classified according to lung transplant volume in 2005-2010, with 8,228 adults (279 on ECMO) who underwent transplants at these centers between June 2010 and June 2015 included in the survival analysis. In multivariable Cox analysis stratified by center, we found that, in historically low-volume centers, ECMO was associated with increased post-transplant mortality hazard (hazard ratio, 1.968; 95% confidence interval, 1.083-3.577; P = 0.026). In contrast, in historically high-volume centers, ECMO had no adverse influence on post transplant survival (hazard ratio, 0.853; 95% confidence interval, 0.596-1.222; P = 0.386). CONCLUSIONS: An adverse effect of ECMO at the time of lung transplant was evident in low-volume centers but absent in centers with experience of performing more than 170 lung transplants in the first 5 years of the lung allocation score era. PMID- 26840157 TI - A study of the vitreoretinal interface in patients with age-related macular degeneration. AB - PURPOSE: To assess whether hyaloid adhesion is more prevalent in patients with age-related macular degeneration (AMD) than in control patients and to evaluate whether it is more prevalent in exudative AMD than in non-exudative AMD. METHODS: This was a cross-sectional, controlled analytical study. Patients from the Ophthalmology Department of the Public Service Hospital of the State of Sao Paulo were included if they were diagnosed with AMD that was confirmed by fundus biomicroscopy and fluorescein angiography. Patients were divided into three groups: patients without a vitreoretinal disease (controls), patients with exudative AMD, and patients with non-exudative AMD. For the optimal study of the vitreoretinal interface, all patients were subjected to spectral-domain optical coherence tomography (SD-OCT; Cirrus HD-OCT, version 4000; Carl Zeiss Meditec) and ultrasonography (UltraScan(r), Alcon). Results with p values of <=0.05 were considered statistically significant. RESULTS: We assessed 75 eyes of 23 patients with AMD (14 women and nine men) and 15 the control patients (11 women and four men). In total, 33 eyes had AMD that was consistent with the inclusion criteria, of which 11 had the non-exudative form (non-atrophic) and 22 had the exudative form (11 active and 11 disciform scars). Adherence was observed in eight eyes in the control group (26.67%), in seven eyes with exudative AMD (31.82%), and in five eyes with non-exudative AMD (45.45%). CONCLUSION: Patients with exudative and non-exudative forms of AMD did not present with higher vitreoretinal adhesion than control patients as assessed by SD-OCT and ultrasound. Moreover, patients with exudative AMD (neovascular membrane and disciform scar) did not reveal a higher adherence than those with non-exudative AMD when evaluated by the same methods. PMID- 26840156 TI - Ophthalmological findings in infants with microcephaly and presumable intra uterus Zika virus infection. AB - PURPOSE: In 2015, a twenty-fold increase in the prevalence of microcephaly in Brazil was reported, and the Ministry of Health associated this abnormal prevalence with the maternal-fetal Zika virus (ZIKV) transmission. METHODS: We assessed the ophthalmological findings of ten mothers and their infants that had been clinically diagnosed with ZIKV-related microcephaly and presented ocular abnormalities, born from May to December 2015. RESULTS: Seven mothers (70.0%) referred symptoms during pregnancy (malaise, rash and arthralgia), of which six (85.7%) were in the first trimester. At the time of exam, no ophthalmological abnormalities were identified in the mothers and they did not report ocular symptoms during pregnancy. Serology was negative in all infants for Toxoplasmosis, Rubella, Cytomegalovirus, Syphilis and Human Immunodeficiency Viruses. Ocular findings included macular alterations (gross pigment mottling and/or chorioretinal atrophy) in fifteen eyes (75.0%), and optic nerve abnormalities (hypoplasia with double-ring sign, pallor, and/or increased cup-to disk ratio) in nine eyes (45.0%). CONCLUSIONS: Patients presented normal anterior segment and important macular and optic nerve abnormalities. Further studies will assess the visual significance of these alterations. PMID- 26840158 TI - Serous retinal detachment in patients with macular edema secondary to branch retinal vein occlusion. AB - PURPOSE: The aim of the present study was to evaluate visual acuity (VA) and central macular thickness (CMT) to assess the influence of serous retinal detachment (SRD) in eyes with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: Sixty-one eyes with BRVO from 61 patients with ME were analyzed and divided into two groups according to the spectral domain optical coherence tomography (OCT) findings of SRD and cystoid macular edema (CME). All patients underwent complete ophthalmic examinations and OCT measurements (Cirrus, Carl Zeiss Meditec Inc, Dublin, CA). Patients with marked retinal hemorrhage, diabetic retinopathy, previous laser photocoagulation, and/or intravitreal injection were excluded. RESULTS: The mean age of included patients (37 males, 24 females) was 65.4 +/- 11.4 (53-77) years. There were 21 patients with SRD and 40 patients with CME. All of the 21 patients with SRD had CME. VA was significantly worse in the SRD group compared with the CME (non-SRD) group (0.82 +/- 0.34 logMAR vs 0.64 +/- 0.38 logMAR; P=0.005). Conversely, CMT was significantly greater in the SRD group than in the CME group (465 +/- 115 u vs 387 +/- 85 u; P=0.00004). CONCLUSION: SRD may be associated with decreased VA. The prognosis of patients with BRVO and SRD requires further investigation. PMID- 26840159 TI - Mean platelet volume in patients with retinal artery occlusion. AB - PURPOSE: The aim of this study was to investigate the mean platelet volume (MPV) of patients with retinal artery occlusion (RAO). METHODS: Thirty-seven patients diagnosed with RAO and 32 control subjects were included in this retrospective study. Retinal artery occlusion was diagnosed on the basis of clinical examination and fundus fluorescein angiography. All participants underwent complete ocular examination, and MPV, hematocrit, hemoglobin, and platelet counts were recorded. RAO patient data were compared with those of the control subjects. RESULTS: Patients with RAO had significantly higher MPV values (7.96 +/- 1.2 fL) compared with control subjects (7.33 +/- 0.7 fL, p<0.001). No significant difference was found with regard to platelet count between the RAO group and the control group (262 +/- 70.1 * 109/L and 251 +/- 56.6 * 109/L, respectively, p=0.50). MPV was an independent predictor of RAO [odds ratio (OR)=0.50; 95% confidence interval (CI)=0.28-0.89; p=0.019). CONCLUSIONS: Our results demonstrated that MPV values were significantly higher in patients with RAO, suggesting that larger platelets may contribute to the pathogenesis of the RAOs. PMID- 26840160 TI - Comparison of pain scores between patients undergoing panretinal photocoagulation using navigated or pattern scan laser systems. AB - PURPOSE: To compare the pain responses of patients with proliferative diabetic retinopathy (PDR) undergoing panretinal photocoagulation (PRP) using either pattern scan laser (PASCAL) or navigated laser photocoagulation (NAVILAS). METHODS: Patients diagnosed with PDR were randomly assigned to undergo either PASCAL or NAVILAS photocoagulation treatment. PRP was performed using the multi shot mode with a spot size of 200-400 um and a pulse duration of 30 ms to obtain a white-grayish spot on the retina. Parameters were identical in both procedures. After 30 min of PRP application, patients were asked to verbally describe their pain perception as either "none," "mild," "moderate," "severe," or "very severe" using a verbal rating scale (VRS) and visual analog scale (VAS) by indicating a score from "0" to "10," representing the severity of pain from "no pain" to "severe pain." RESULTS: A total of 60 eyes of 60 patients (20 females and 40 males) diagnosed with PDR were treated. The mean age of patients was 62.22 +/- 9.19 years, and the mean diabetes duration was 195.47 +/- 94.54 months. The mean number of laser spots delivered during PRP was 389.47 +/- 71.52 in the NAVILAS group and 392.70 +/- 54.33 in the PASCAL group (p=0.57). The difference in pain responses between patients in the NAVILAS and PASCAL groups was significant with regard to the mean VRS (1.10 +/- 0.67 and 1.47 +/- 0.69, respectively; p=0.042) and mean VAS (2.13 +/- 1.17 and 2.97 +/- 1.35, respectively; p=0.034) scores. CONCLUSIONS: Pain responses in patients undergoing PRP with a 30-ms pulse duration were significantly milder in the NAVILAS group than in the PASCAL group. PMID- 26840161 TI - Congenital and developmental cataract: axial length and keratometry study in Brazilian children. AB - PURPOSE: To evaluate the ocular axial length (AL) and keratometry (K) in Brazilian children with congenital/developmental cataract, assess the differences and evolution of AL and K according to age, and establish functional models of AL and K as function of age. METHODS: Children with congenital/developmental cataract aged 1.5 months old to 8 years old and no other ocular diseases were included. All eyes with unilateral cataract, the left eyes from children with bilateral cataracts, and healthy eyes from children with unilateral cataract were analyzed. After the administration of anesthesia, K was measured with a portable automatic keratometer, and AL was measured with a contact biometer. Cataract surgery was performed immediately after the measurements were taken. The data were statistically analyzed, and a linear regression with an age logarithm was used to model the relationship. RESULTS: Forty-four eyes with cataract were included in this analysis, comprising 15 eyes with unilateral cataract and 29 left eyes from children with bilateral cataracts. The mean age was 27.3 months with a mean AL of 20.63 +/- 2.11 mm and a mean K of 44.94 +/- 2.44 D. The K value was significantly steeper and the AL value was significantly shorter in younger children (P< 0.001). No significant differences were found neither between eyes with unilateral and bilateral cataracts nor between eyes with unilateral cataract and their corresponding healthy eyes (P >0.05). CONCLUSION: The values of K and AL significantly change with age, especially during the first 6 months of life. A linear functional relationship between K and AL with the logarithm of age and between K and AL was established. PMID- 26840162 TI - Sociodemographic status of severely disabled and visually impaired elderly people in Turkey. AB - PURPOSE: To identify the prevalence of ophthalmologic diseases in elderly patients who had been classified as severely disabled and to identify the ophthalmologic conditions leading to visual impairment and blindness. METHODS: The medical records of 2806 patients who had applied to the Health Board of the Erzurum Region Training and Research Hospital between January 2011 and December 2012 were reviewed. One hundred ninety-nine patients aged >64 years who were classified as severely disabled with disability rates of over 50%, and who were unable to care for themselves or to move and/or communicate without help were included in the study. RESULTS: The most frequently seen disabilities were neurological (47.2%) and those resulting from eye diseases (17.1%). The most common ophthalmologic diseases were cataract, glaucoma, and age-related macular degeneration. The mean right and left eye visual acuities were 1.17 +/- 1.10 logMAR and 1.13 +/- 1.0 logMAR, respectively. Of the 60 patients with ophthalmologic diseases or conditions, 33 were blind (visual acuity worse than 20/400) and 10 were visually impaired (visual acuity worse than 20/70 but better than 20/400). Cataracts were the main cause of blindness. The mean age of the patients who were still being followed up at the time of application to the disability board was significantly lower than that of the others (p =0.015). Seventy-nine percent of the blind patients were from rural areas, and 88% of these had no regular follow-up. Among the blind and visually impaired, significantly more patients from urban areas had social security insurance (SSI) than those from rural areas (p =0.043). Nearly 64% of the blind patients were women. The follow-up rate was significantly lower in women (p =0.025). According to multinomial logistic regression analysis, the visually impaired and blind patients were more likely to have lower follow-up rates than the other types of severely disabled patients (OR: 0.231, 95% Cl: 0.077-0.688, p=0.009). CONCLUSIONS: Blindness gives rise to severe disability, and the most common ophthalmologic diseases that cause severe disabilities in elderly patients are cataract, glaucoma, and age-related macular degeneration. Sociodemographic factors that may affect the accessibility of visually impaired and blind people to health services include their place of residence and gender. PMID- 26840163 TI - Intrastromal corneal ring segments delay corneal grafting in patients with keratoconus. AB - PURPOSE: To assess the impact of intrastromal corneal ring segments (ICRS) as a surgical alternative to corneal grafting in patients with keratoconus who were scheduled for a corneal transplant. METHODS: This single-surgeon, single-center, retrospective, observational case series study included 19 eyes of 18 patients (mean age, 23.36 +/- 6.22 years) with a confirmed diagnosis of keratoconus. These patients were enrolled from the State of Goias, Brazil corneal graft waiting list. Following extensive pre-operative testing, including the measurement of best-corrected visual acuity (BCVA), applanation tonometry, biomicroscopy, funduscopy, pachymetry, and corneal topography, patients were implanted with Keraring(r) ICRS. Patients underwent clinical examination at postoperative days 1, 7, 30, 90, and 180 and were examined again 2 years following surgery. RESULTS: At the 2-year cut-off following ICRS implantation (mean follow-up, 28.72 +/- 4.71 months), there was a statistically significant improvement in BCVA (logMAR) from 0.59 +/- 0.35 preoperatively to 0.35 +/- 0.45 postoperatively ( p <0.01). Three of 19 eyes (15.8%) still required keratoplasty. In the remaining patients (84.2%), BCVA was managed with spectacles (52.6%) or contact lenses (31.6%). One patient developed infectious keratitis, requiring removal of ICR at the first postoperative visit. CONCLUSION: ICRS implantation may be a surgical alternative to keratoplasty in patients with keratoconus. This procedure may delay or even eliminate the need for keratoplasty in such patients. PMID- 26840164 TI - Effects of prostaglandin analogs on blood flow velocity and resistance in the ophthalmic artery of rabbits. AB - PURPOSE: The aim of this study was to investigate the effects of prostaglandin analogs on blood flow in the ophthalmic artery of clinically healthy rabbits. METHODS: Fifty-five clinically healthy New Zealand white rabbits were divided into six groups, and the left eyes were treated for four weeks with the preservative benzalkonium chloride (BAK) only or a topical formulation of different prostaglandin analogs (bimatoprost BAK, tafluprost BAK-free, travoprost BAK, travoprost POLYQUAD, and latanoprost BAK). Color Doppler imaging was performed before and after the treatments. The mean values of the peak systolic velocity (PSV) and end diastolic velocity and the resistive index (RI) were calculated. Statistical analysis was performed to compare the differences pre- and post-treatment for each drug and post-treatment among the drugs. RESULTS: The prostaglandin analogs did not affect PSV. Bimatoprost BAK, travoprost POLYQUAD, and latanoprost BAK did not change RI. Tafluprost BAK-free and travoprost BAK therapy resulted in similar reductions in RI. No significant differences pre- and post-treatment were found when BAK was administered alone. CONCLUSION: The prostaglandin analogs tafluprost BAK-free and travoprost BAK improved blood flow in the ophthalmic artery in healthy New Zealand white rabbits, which suggests that these drugs enhance the prevention of the progression the progression of glaucoma. PMID- 26840165 TI - Characterization of cryopreserved primary human corneal endothelial cells cultured in human serum-supplemented media. AB - PURPOSE: To compare cryopreserved human corneal endothelial cells (HCECs) grown in human serum-supplemented media (HS-SM) with cryopreserved HCECs grown in fetal bovine serum-supplemented media (FBS-SM). METHODS: Three pairs of human corneas from donors aged 8, 28, and 31 years were obtained from the eye bank. From each pair, one cornea was used to start a HCEC culture using HS-SM; the other cornea was grown in FBS-SM. On reaching confluence, the six cell populations were frozen using 10% dimethyl sulfoxidecontaining medium. Thawed cells grown in HS-SM were compared with those grown in FBS-SM with respect to morphology, growth curves, immunohistochemistry, real time-reverse transcriptase polymerase chain reaction (RT-PCR) for endothelial cell markers, and detachment time. RESULTS: No difference in morphology was observed for cells grown in the two media before or after cryopreservation. By growth curves, cell counts after thawing were similar in both media, with a slight trend toward higher cell counts in FBS-SM. Cells grown in both the media demonstrated a similar expression of endothelial cell markers when assessed by immunohistochemistry, although HCEC marker gene expression was higher in cells grown in HS-SM than in those grown in FBS-SM as assessed by RT-PCR. With FBS-SM, there was a tendency of longer detachment time and lower cell passages. CONCLUSIONS: HS-SM was similar to FBS-SM for cryopreservation of cultured HCECs as assessed by analysis of cell morphology, proliferation, and protein expression, although marker gene expression was higher in cells grown in HS-SM than in those grown in FBS-SM. Detachment time was longer with FBS-SM and in lower passages. PMID- 26840166 TI - Contact lens fitting in a patient with Alport syndrome and posterior polymorphous corneal dystrophy: a case report. AB - Alport Syndrome is a hereditary disease that is caused by a gene mutation and affects the production of collagen in basement membranes; this condition causes hemorrhagic nephritis associated with deafness and ocular changes. The X-linked form of this disease is the most common and mainly affects males. Typical ocular findings are dot-and-fleck retinopathy, anterior lenticonus, and posterior polymorphous corneal dystrophy. Some cases involving polymorphous corneal dystrophy and corneal ectasia have been previously described. Here we present a case report of a 33-year-old female with Alport syndrome, posterior polymorphous corneal dystrophy, and irregular astigmatism, whose visual acuity improved with a rigid gas permeable contact lens. PMID- 26840167 TI - Aniridia after blunt trauma and presumed wound dehiscence in a pseudophakic eye. AB - This was a report about a pseudophakic patient who experienced isolated total aniridia without damage to other intraocular structures following blunt trauma to the eye. This patient had a history of uneventful cataract surgery using a small clear corneal incision (CCI). This 71-year-old male presented at our clinic with glare in his left eye. He reported that he had fallen down while drunk and struck his left eye against a stone on the road 15 days earlier. He had undergone cataract surgery on his left eye nine months before the accident at another eye clinic. Slit-lamp examination showed total aniridia in his left eye, but there was no hyphema or cells in the anterior chamber. The intraocular lens in his left eye was stable, without decentration, dislocation, or zonular dehiscence and remained in an intact capsular bag. Review of the medical records from the surgical clinic at which he had undergone cataract surgery indicated no specific findings for any intraocular structure including the iris. He had previously undergone an uneventful phacoemulsification for his left eye through a 2.2 mm CCI, followed by the implantation of a single piece acrylic intraocular lens inside an intact capsular bag. This report showed that small-sized CCIs can be opened postoperatively by trauma and that this can result in isolated total aniridia without damage to other intraocular structures. PMID- 26840168 TI - Using thermography for an obstruction of the lower lacrimal system. AB - Obstructions in the lacrimal pathways quite often require accurate and reliable image scanning for confirmation and documentation. Infrared thermal imaging, known as thermography, is a resource that complements diagnosis; it does not require touching the patient or applying contrast materials and has been used in various medical procedures for decades. However, there have been few studies in the literature about its use in ophthalmology. In this paper, the authors have presented a case of dacryocystitis where the obstruction of the lacrimal punctum was so acute that conventional dacryocystography could not be used. The authors have successfully reported the use of thermography as a complementary propaedeutic and will discuss the method they used. PMID- 26840169 TI - Choroidal melanoma recurrence after episcleral brachytherapy and transpupillary thermotherapy. AB - A 68-year-old man diagnosed with choroidal melanoma (CM) in the right eye underwent treatment with episcleral brachytherapy (I125) and transpupillary thermotherapy. Ultrasound, computed tomography, and magnetic resonance imaging were performed and revealed ocular recurrence of CM. Treatment with extended enucleation was performed. Macroscopic and microscopic examinations revealed extraocular extension and malignant cells, respectively. Immunohistochemistry demonstrated tumoral Melan-A and HMB-45 expression. No cytogenic abnormalities were detected with fluorescence in situhybridization of tumor cells using probes against chromosomes 3q27 and 8q24. The patient underwent adjuvant external beam radiotherapy for treatment of residual tumor tissue. This case represents the first reported case of recurrent CM with no cytogenetic abnormalities and the absence of metastatic disease, despite a number of the poorest prognostic factors. PMID- 26840170 TI - Early post-LASIK flap amputation in the treatment of aggressive, branching keratitis: a case report. AB - Infectious keratitis is rare following laser vision correction. We present a case of aggressive fungal keratitis caused by Aspergillus flavus, following laser in situ keratomileusis (LASIK) in the setting of a unique environmental risk factor. We describe the key features of the acute case presentation, which guided empirical medical and surgical treatment, resulting in the most favorable outcome found in the literature, to date. PMID- 26840171 TI - Combined transscleral fixation of an artificial iris prosthesis with an intraocular lens. AB - Post-traumatic aniridia combined with aphakia may be seen after globe injury. Aside from esthetic aspects, partial or total loss of the iris tissue may also be related to various degrees of glare and photophobia. Such patients suffer from severe visual impairment secondary to aphakia. Herein we describe a novel surgical technique for the management of an aphakic eye with traumatic aniridia for a patient who underwent transscleral fixation of a custom-tailored artificial iris prosthesis combined with a rigid intraocular lens (IOL). Tight suturing of the IOL haptic eyelets on the silicone iris prosthesis and fixation of such a complex to the scleral wall may provide excellent cosmetic and functional outcomes in aphakic eyes with aniridia. PMID- 26840173 TI - Preoperative usage of ultrasound biomicroscopy in pediatric cataract. PMID- 26840172 TI - Vitamin A and the eye: an old tale for modern times. AB - Clinical presentations associated with vitamin A deficiency persist in poor regions globally with the same clinical features as those described centuries ago. However, new forms of vitamin A deficiency affecting the eyes, which have become widespread, as a result of modern societal habits are of increasing concern. Ophthalmic conditions related to vitamin A deficiency require the combined attention of ophthalmologists, pediatricians, internists, dermatologists, and nutritionists due to their potential severity and the diversity of causes. As the eyes and their adnexa are particularly sensitive to vitamin A deficiency and excess, ocular disturbances are often early indicators of vitamin A imbalance. The present review describes the clinical manifestations of hypovitaminosis A with an emphasis on so-called modern dietary disorders and multidisciplinary treatment approaches. The present review also discusses the relationship between retinoic acid therapy and dry eye disease. PMID- 26840174 TI - Zika virus-related hypertensive iridocyclitis. PMID- 26840175 TI - Oliver Sacks and his legacy to vision science and ophthalmology. PMID- 26840176 TI - Development of glycan specific lectin based immunoassay for detection of prostate specific antigen. AB - We describe an analytical approach for the detection and verification of glycosylation patterns of prostate specific antigen (PSA), a key biomarker currently used for understanding the onset and prognosis of prostate cancer. PSA has been purified from the human seminal plasma and total PSA from prostate cancer sera. PSA is a monomeric glycoprotein with an apparent molecular mass 28040.467 Da, which exhibits a characteristic protease activity against casein and gelatin. Its optimal protease activity is centered on neutral pH. Peptide mass fingerprint analysis of the purified PSA has yielded peptides that partially match with known database sequences (Uniprot ID P07288). Tryptic digestion profile of isolated PSA, infer the exclusive nature of PSA and may be additive molecule in the dictionary of seminal proteins. Surface plasmon resonance and lectin immunoassay revealed direct interaction between a newly developed anti-PSA monoclonal antibody (C4E6) and PSA. A lectin based immunoassay is reported here which was achieved with the C4E6 anti-PSA antibody and biotinylated plant lectins. This investigation provides an alternative method to isolate and quantify PSA with altered glycosylation which might be seen in the prostate cancer and developing a lectin based immunoassay to detect PSA in serum of prostate cancer patients. PMID- 26840177 TI - Investigating a galactomannan gel obtained from Cassia grandis seeds as immobilizing matrix for Cramoll lectin. AB - Characterization, with emphasis on the rheological properties, of Cassia grandis seeds galactomannan gel containing immobilized Cramoll 1-4 is presented. The gels, with and without immobilized Cramoll 1-4, were evaluated along time by rheometry, pH, color, microbial contamination and lectin hemagglutinating activity (HA). Rheological determinations confirmed the gels to be very stable up to 30 days with variations occurring after this period. Rheological data also showed that the gel/Cramoll 1-4 immobilizing matrix loses its elastic modulus substantially after 60 days. Both gels presented no microbial contamination as well as a pH close to neutral. Colorimetric parameters demonstrated the gels transparency with occasional yellowness. The opacity of the galactomannan gel did not change significantly along the study; the same did not occur for the gel with immobilized Cramoll 1-4 as a statistically significant reduction of its opacity was observed. In what concerns immobilized Cramoll 1-4 HA, up to 90% of its initial HA was maintained after 20 days, with a decrease to 60% after 60 days. These results combined with the thickening and stabilizing characteristics of the galactomannan gel make this gel a promising immobilizing matrix for Cramoll 1-4 that can be further exploited for clinical and cosmetic applications. PMID- 26840178 TI - Identification and characterization of an acidic and acid-stable endoxyloglucanase from Penicillium oxalicum. AB - Xyloglucan is a major structural macromolecule of the primary cell wall of spermatophytes. The hydrolysis of xyloglucan by xyloglucanases may facilitate the hydrolysis of cellulose by cellulases, which is beneficial for bioethanol production. Penicillium oxalicum has been employed for commercial cellulase production. In P. oxalicum, many genes and proteins related to the degradation of structural macromolecules of the plant cell wall have been found, but no gene encoding a xyloglucanase has been identified. In this study, a gene, PoxXEG12A, was cloned from P. oxalicum and expressed in Pichia pastoris, and the gene product was enzymatically characterized. PoxXEG12A shared 63% sequence identity with endoxyloglucanases from Aspergillus niger and Aspergillus aculeatus. PoxXEG12A specifically hydrolyzed tamarind xyloglucan in endo-acting mode and, thus, it is an endoxyloglucanase. PoxXEG12A was most active at pH 4.5-5.5 and at 55-60 degrees C, with a specific activity of 172 U/mg protein toward tamarind xyloglucan. The enzyme was stable at pH 3.5-7.0 and below 40 degrees C. The properties of the endoxyloglucanase PoxXEG12A suggest that the enzyme might have potential in industrial applications. PMID- 26840180 TI - Correction: Transgenic shRNA pigs reduce susceptibility to foot and mouth disease virus infection. PMID- 26840179 TI - Remediation of distilleries wastewater using chitosan immobilized Bentonite and Bentonite based organoclays. AB - Organic-inorganic nanocomposite, namely chitosan immobilized Bentonite (CIB) with chitosan content of 5% was synthesized in an acetic acid solution (2%). Organically modified CIB and Bentonite (mbent.) were prepared by intercalating cetyl trimethylammonium bromide (CTAB) as a cationic surfactant at doses equivalent to 1.5 and 3 times the cation exchange capacity (CEC) of clay. The prepared samples were characterized using FTIR, XRD and SEM to explore the interlayer structure and morphology of the resultant nanocomposites. The remediation of distilleries (vinasse) wastewater process was carried out using different adsorbents including CIB, modified CIB (mCIB), Bentonite (bent.), modified Bentonite (mbent.) and chitosan at different contact time. The results showed that the packing density of surfactant used in the synthesis of organoclays strongly affects the sorption capacity of the clay mineral and also showed that (mCIB)3 was found to be the most effective sorbent in the purification of distilleries wastewater with 83% chemical oxygen demand (COD) reduction and 78% color removal. PMID- 26840181 TI - Balancing the Budget: Accounting for Glucocorticoid Bioactivity and Fate during Water Treatment. AB - Numerous studies have identified the presence and bioactivity of glucocorticoid receptor (GR) active substances in water; however, the identification and activity-balance of GR compounds remained elusive. This study determined the occurrence and attenuation of GR bioactivity and closed the balance by determining those substances responsible. The observed in vitro GR activity ranged from 39 to 155 ng dexamethasone-equivalent/L (ng Dex-EQ/L) in the secondary effluents of four wastewater treatment plants. Monochromatic ultraviolet light of 80 mJ/cm(2) disinfection dose was efficient for GR activity photolysis, whereas chlorination could not appreciably attenuate the observed GR activity. Ozonation was effective only at relatively high dose (ozone/TOC 1:1). Microfiltration membranes were not efficient for GR activity attenuation; however, reverse osmosis removed GR activity to levels below the limits of detection. A high-sensitivity liquid chromatography with tandem mass spectrometry (LC-MS/MS) method was then developed to screen 27 GR agonists. Twelve were identified and quantified in effluents at summed concentrations of 9.6-21.2 ng/L. The summed Dex-EQ of individual compounds based on their measured concentrations was in excellent agreement with the Dex-EQ obtained from bioassay, which demonstrated that the detected glucocorticoids can entirely explain the observed GR bioactivity. Four synthetic glucocorticoids (triamcinolone acetonide, fluocinolone acetonide, clobetasol propionate, and fluticasone propionate) predominantly accounted for GR activity. These data represent the first known publication where a complete activity balance has been determined for GR agonists in an aquatic environment. PMID- 26840183 TI - Specific ion modulated thermoresponse of poly(N-isopropylacrylamide) brushes. AB - The influence of specific anions on the equilibrium thermoresponse of poly(N isopropylacrylamide) (pNIPAM) brushes has been studied using in situ ellipsometry, quartz crystal microbalance with dissipation (QCM-D) and static contact angle measurements between 20 and 45 degrees C in the presence of up to 250 mM acetate and thiocyanate anions in water. The thickness and changes in dissipation exhibited a broad swelling transition spanning approximately 15 degrees C from collapsed (high temperatures) to swollen conformation (low temperatures) while the brush surface wettability changed over approximately 2 degrees C. In the presence of the kosmotropic acetate anions, the measured lower critical solution temperature (LCST) by the three techniques was very similar and decreased linearly as a function of ionic strength. Conversely, increasing the concentration of the chaotropic thiocyanate anions raised the LCST of the pNIPAM brushes with variation in the measured LCST between the three techniques increasing with ionic strength. The thickness of the pNIPAM brush was seen to progressively increase with increasing thiocyanate concentration at all temperatures. It is proposed that specific ion binding of the chaotropic thiocyanate anion with pNIPAM amide moieties increases the electrostatic intra- and intermolecular repulsion within and between pNIPAM chains. This allows the brush to begin to swell at higher temperatures and to an overall greater extent. PMID- 26840182 TI - Transcriptome Analysis of the SL221 Cells at the Early Stage during Spodoptera litura Nucleopolyhedrovirus Infection. AB - Spodoptera litura (S. litura) is one of the most destructive agricultural pests worldwide. There is urgent need for a nuclear polyhedrosis virus that is specific to S. litura. To date, there have been no reports regarding the responses of S. litura cells to early Spodoptera litura nucleopolyhedrovirus (SpltNPV) infection due to the lack of a reference genome and transcriptome for S. litura. In this study, a cell transcriptome from the host S. litura was assembled and used for Illumina strand-specific RNA sequencing (RNA-seq) to generate 99180 unigenes, representing the 18 hour infection cycle. More than 2000 S. litura genes were significant differentially regulated throughout the infection. The levels of viral mRNAs began to increase dramatically at 6 hpi, and this increase continued throughout the remainder of the infection. We focused on the expression of genes related to stress responses, apoptosis, metabolic enzymes and host cell innate immune system. A small subset of genes related to host stress response, especially for 62 ones being able to annotated as enzyme, ligand and receptor genes, were observed to be specifically differentially expressed at 6 hpi. At 18 hpi, 104 unigenes were continuously significantly changing from 0 hpi to 18 hpi, considered to be viral multiplication related genes, including 3 annotated SL221 unigenes and 81 viral genes, such as tetraspanin and iap gene. This information and further studies on the regulation of host gene expression by baculovirus infection at early stage will provide the tools needed to enhance the utility of this virus as an effective insecticide. PMID- 26840185 TI - The difference between oats and beta-glucan extract intake in the management of HbA1c, fasting glucose and insulin sensitivity: a meta-analysis of randomized controlled trials. AB - Increasing oats and beta-glucan extract intake has been associated with improved glycemic control, which is associated with the reduction in the development of diabetes. This study aims to assess the different effects between oat (whole and bran) and beta-glucan extract intake on glycemic control and insulin sensitivity. PubMed, Embase, Medline, The Cochrane Library, CINAHL and Web of Science were searched up to February 2014. We included randomized controlled trials with interventions that lasted at least four weeks that compared oats and beta-glucan (extracted from oats or other sources) intake with a control. A total of 1351 articles were screened for eligibility, and relevant data were extracted from 18 studies (n = 1024). Oat product dose ranged from 20 g d(-1) to 136 g d(-1), and beta-glucan extract dose ranged from 3 g d(-1) to 10 g d(-1). Compared with the control, oat intake resulted in a greater decrease in fasting glucose and insulin of subjects (P < 0.05), but beta-glucan extract intake did not. Furthermore, oat intake resulted in a greater decrease in glycosylated hemoglobin (HbA1c) (P < 0.001, I(2) = 0%) and fasting glucose (P < 0.001, I(2) = 68%) after removing one study using a concentrate and a different design and fasting insulin of type 2 diabetes (T2D) (P < 0.001, I(2) = 0%). The intake of oats and beta-glucan extracted from oats were effective in decreasing fasting glucose (P = 0.007, I(2) = 91%) and fasting insulin of T2D (P < 0.001, I(2) = 0%) and tented to lower HbA1c (P = 0.09, I(2) = 92%). Higher consumption of whole oats and oat bran, but not oat or barley beta-glucan extracts, are associated with lower HbA1c, fasting glucose and fasting insulin of T2D, hyperlipidaemic and overweight subjects, especially people with T2D, which supports the need for clinical trials to evaluate the potential role of oats in approaching to the management of glycemic control and insulin sensitivity of diabetes or metabolic syndrome subjects. PMID- 26840186 TI - Ataluren for the treatment of cystic fibrosis. AB - Alleles causing diseases that carry premature termination codons (PTCs) will cause premature cessation of translation, leading to loss of function and consequent disease. Recently, a novel agent, Ataluren, was developed through a high throughput screening program. Ataluren is orally bioavailable and was shown to be effective in Cystic Fibrosis (CF). Phase I and II studies established the safety and dosing regimens for Ataluren. The results of a short study showed modest improvements in pulmonary function and a reduction in quantitative cough assessment. There was improvement in nasal potential difference and nasal epithelial CFTR protein. In a phase III trial this effect was not observed in patients that were concomitantly treated with tobramycin inhalation. Following these positive findings, a multinational Phase III placebo-controlled efficacy trial is currently underway. PMID- 26840184 TI - Estimated Trans-Lamina Cribrosa Pressure Differences in Low-Teen and High-Teen Intraocular Pressure Normal Tension Glaucoma: The Korean National Health and Nutrition Examination Survey. AB - BACKGROUND: To investigate the association between estimated trans-lamina cribrosa pressure difference (TLCPD) and prevalence of normal tension glaucoma (NTG) with low-teen and high-teen intraocular pressure (IOP) using a population based study design. METHODS: A total of 12,743 adults (>= 40 years of age) who participated in the Korean National Health and Nutrition Examination Survey (KNHANES) from 2009 to 2012 were included. Using a previously developed formula, cerebrospinal fluid pressure (CSFP) in mmHg was estimated as 0.55 * body mass index (kg/m2) + 0.16 * diastolic blood pressure (mmHg)-0.18 * age (years)-1.91. TLCPD was calculated as IOP-CSFP. The NTG subjects were divided into two groups according to IOP level: low-teen NTG (IOP <= 15 mmHg) and high-teen NTG (15 mmHg < IOP <= 21 mmHg) groups. The association between TLCPD and the prevalence of NTG was assessed in the low- and high-teen IOP groups. RESULTS: In the normal population (n = 12,069), the weighted mean estimated CSFP was 11.69 +/- 0.04 mmHg and the weighted mean TLCPD 2.31 +/- 0.06 mmHg. Significantly higher TLCPD (p < 0.001; 6.48 +/- 0.27 mmHg) was found in the high-teen NTG compared with the normal group. On the other hand, there was no significant difference in TLCPD between normal and low-teen NTG subjects (p = 0.395; 2.31 +/- 0.06 vs. 2.11 +/- 0.24 mmHg). Multivariate logistic regression analysis revealed that TLCPD was significantly associated with the prevalence of NTG in the high-teen IOP group (p = 0.006; OR: 1.09; 95% CI: 1.02, 1.15), but not the low-teen IOP group (p = 0.636). Instead, the presence of hypertension was significantly associated with the prevalence of NTG in the low-teen IOP group (p < 0.001; OR: 1.65; 95% CI: 1.26, 2.16). CONCLUSIONS: TLCPD was significantly associated with the prevalence of NTG in high-teen IOP subjects, but not low-teen IOP subjects, in whom hypertension may be more closely associated. This study suggests that the underlying mechanisms may differ between low-teen and high-teen NTG patients. PMID- 26840187 TI - Assessment of anatomical knowledge by practical examinations: The effect of question design on student performance. AB - The objective structural practical examination (OSPE) is a timed examination that assesses topographical and/or applied knowledge of anatomy with the use of cadaveric resources and medical images. This study investigated whether elements of question design (provision of clinical context, type of visual resources used, gender context, and difficulty) of an anatomy question affected students' performance and also whether there was any effect of basic demography or participation in various voluntary activities. Study participants were second year medical students (n = 150), 83 of whom consented to fill in a questionnaire collecting demographics, revision preferences, and assessment preferences. The examination scores were matched with students' responses collected on the questionnaire and all data analyzed by multiple linear regression. Difficulty of the question was the only design element found to be significantly associated with the number of students that answered correctly (P = 0.001); clinical context, visual resources used and gender of the question were not significant. When individual students' marks were analyzed along with the questionnaire data, only the students' interest in participating in department's demonstrator program was a significant predictor of a high individual score, gender of the students showed a strong trend toward significance, with female students scoring on average higher than male students. The two part OSPE questions were dissociated and analyzed using binary logistic regression to determine whether a correct answer to Part 1 (identification of a tagged or pinned anatomical structures on a specimen or medical image) was predictive of a correct answer to Part 2 (assessment of the relevant functional, applied, or clinical knowledge), but no association was found. Anat Sci Educ 9: 446-452. (c) 2016 American Association of Anatomists. PMID- 26840189 TI - Overexpression of CD61 promotes hUC-MSC differentiation into male germ-like cells. AB - OBJECTIVES: Previous studies have shown that germ-like cells can be induced from human umbilical cord mesenchymal stem cell (hUC-MSCs) in vitro. However, induction efficiency was low and a stable system had not been built. CD61, also called integrin-beta3, plays a significant role in cell differentiation, in that CD61-positive-cell-derived pluripotent stem cells easily differentiate into primordial germ-like cells (PGC). Here, we have explored whether overexpression of CD61 would promote hUC-MSC differentiation into PGC and male germ-like cells. MATERIALS AND METHODS: hUC-MSCs were cultured and transduced using pCD61-CAGG TRIP-pur (oCD61) and pTRIP-CAGG plasmid (Control), and hUC-MSCs overexpressed CD61 were induced by bone morphogenetic protein 4 (BMP4, 12.5 ng/ml), to differentiate into PGC and male germ cells. Quantitative real-time PCR (RT-qPCR), western blotting and immunofluorescence staining were used to examine PGC- and germ cell-specific markers. RESULTS: High expression levels of PGC-specific markers were detected in oCD61 hUC-MSCs compared to controls. After BMP4 induction, expression levels of male germ cell markers such as Acrosin (ACR), Prm1 and meiotic markers including Stra8, Scp3 in oCD61 were significantly higher than those of the Control group. CONCLUSIONS: Under induction of BMP4, CD61 overexpressing hUC-MSCs, which had turned into PGC-like cells, could be further differentiated into male germ-like cells. Thus, a simple and efficient approach to study male germ cell development by using hUC-MSCs has been established. PMID- 26840188 TI - Evaluating the safety and the effects on colonic compliance of neostigmine during motility testing in patients with chronic constipation. AB - BACKGROUND: Neostigmine, an acetyl cholinesterase inhibitor, stimulates colonic motor activity and may induce vagally mediated cardiovascular effects. Our aim was to evaluate effects of i.v. neostigmine on colonic compliance and its safety in patients with chronic constipation. METHODS: We retrospectively reviewed medical records of a selected group of 144 outpatients with chronic constipation who were refractory to treatment. These patients had undergone intracolonic motility and compliance measurements with an infinitely compliant balloon linked to a barostat. Data abstracted included barostat balloon mean volumes with increases in pressure (4 mmHg steps from 0 to 44 mmHg) before and after i.v. neostigmine. Vital signs and oxygen saturation before and after neostigmine were recorded. KEY RESULTS: Of the 144 patients, 133 were female, mean age was 41.0 +/ 15.4 years (SD), and duration of constipation was 12.9 +/- 13.8 years. Among patients who had undergone colonic transit measurement by scintigraphy, the overall colonic transit at 24 h (geometric center, GC24 [n = 115]) was 1.5 +/- 0.7 (normal >1.3), and at 48 h (GC48 [n = 75]) it was 2.3 +/- 0.9 (normal >1.9). Neostigmine decreased colonic compliance at lower distension pressures (e.g., 12 and 20 mmHg [both p < 0.001]), but not at 40 mmHg. There were expected minor changes in vital signs in response to neostigmine in 144 patients; however, one patient developed unresponsiveness, significant bradycardia, hypotension, and muscular rigidity that responded to 400 mcg i.v. atropine. CONCLUSIONS & INFERENCES: Neostigmine significantly decreases colonic compliance in patients with refractory chronic constipation. Symptomatic bradycardia in response to neostigmine should be promptly reversed with atropine. PMID- 26840190 TI - Nurses' Perspectives on Patient Satisfaction and Expectations: An International Cross-Sectional Multicenter Study With Implications for Evidence-Based Practice. AB - BACKGROUND: Addressing patient expectations is necessary to achieve high satisfaction. However, few data are available on nurses' perceptions and performance with respect to patient expectations and satisfaction. OBJECTIVES: This international multicenter study aimed to: (a) evaluate nurses' attitudes and performance with respect to patient satisfaction and expectations, and (b) identify predictors of nurses' inquiry of patients' satisfaction at the point of discharge. METHODS: A questionnaire examining attitudes and performance toward patient satisfaction and expectations was developed and validated. Nurses at four academic hospitals in the United States, the United Kingdom, Israel, and Denmark were surveyed. RESULTS: A total of 536 nurses participated in the study (response rate 85.3%). Nurses expressed positive attitudes toward activities related to patient satisfaction and expectations, endorsing the importance of talking with patients about their satisfaction status (91.6%) and their expectations (93.2%). More than half of the responders (51.8%) claimed to have responded to the status of patient satisfaction or dissatisfaction (Israel: 25%; United States: 54.9%; United Kingdom: 61.7%; Denmark: 69.9%; p < .001). However, only 12.1% stated that they routinely ask patients about their level of satisfaction, with nurses in the United States (18.3%) and Denmark (17.5%) more likely to ask compared to nurses in the United Kingdom (7.4%) and Israel (6.3%; p = .001). Adjusted logistic regression identified four significant predictors (p < .05) of nurses' inquiry about patients' satisfaction: "Responding to patient's satisfaction status" (OR: 3.1; 95% CI: 1.7-5.8); "Documenting patient's satisfaction status" (OR: 2.8; 95% CI: 1.6-5.1); "Asking routinely about expectations" (OR: 5.4; 95% CI: 3-9.7); and "Responded to expectations during the past month" (OR: 4.3; 95% CI: 1.9-9.4). LINKING EVIDENCE TO ACTION: These findings warrant further investigation, potentially into the nurses' work environments or educational programs, to better understand why nurses' positive attitudes toward patient satisfaction and expectations do not result in actively asking patients about their satisfaction level and what should be done to improve nurses' performance. Healthcare organizations and policy makers should develop and support structured programs to address patient expectations and improve patient satisfaction during hospitalization. PMID- 26840191 TI - High-Deductible Health Plans: Implications for Substance Use Treatment. AB - OBJECTIVE: To examine whether high-deductible health plans are related to patient complexity, health services use, and medical care costs among substance use treatment patients. DATA SOURCE/STUDY SETTING: Electronic health record data from Kaiser Permanente Northern California; 2007-2011. STUDY DESIGN: Retrospective analysis of electronic health record data of substance use treatment patients (N = 31,001). We examined relationship of patient demographics, health comorbidities, and services use and cost to deductible level: none, low ($1 $999), and high (>=$1,000). METHODS: Demographic, membership, diagnostic, and utilization data were merged with cost data. Utilization and costs were summarized into 6-month intervals. Generalized estimation methods for repeated measures with logistic, Poisson, and linear regression were used. PRINCIPAL FINDINGS: Substance use patients with deductible plans were younger and had less comorbidity than those without deductibles. Patients with high deductibles had lower emergency room and hospital use 12- to 6-month pretreatment, but rates became similar to other groups in the 6 months immediately prior to treatment; treatment costs were similar. CONCLUSION: Immediately prior to entering treatment, substance use patients with and without high deductibles have similar patterns of health services utilization. We discuss implications for health policy and treatment, particularly in an era of health reform. PMID- 26840192 TI - Vasovagal Syncope: Hypothesis Focusing on Its Being a Clinical Feature Unique to Humans. AB - Humans live primarily in the upright position; as a result, there is a constant struggle between gravity and needed supply of blood flow to the brain. In certain circumstances brain blood supply may become temporarily insufficient, resulting in syncope. Among the numerous causes of syncope in humans, vasovagal syncope (VVS) is by far the most common. However, despite intensive research, many aspects of the pathophysiology of VVS remain unknown; among these, one of the least well understood is the basis for why VVS is restricted, among vertebrates, to Homo sapiens. In this manuscript we review proposals that have been offered in an attempt to address the issue of the origin of VVS and, although highly speculative, we suggest a new hypothesis (the "brain theory") to try to address the question of why humans, to the exclusion of other species, remain susceptible to VVS. This theory suggests that VVS evolved to offer protection to the brain's functional integrity under certain conditions of severe threat. Although seemingly a disadvantageous evolutionary adaptation, the faint causes the body to take on a gravitationally neutral position, and thereby provides a better chance of restoring brain blood supply and preserving long-term brain function. PMID- 26840193 TI - Undeniable Confirmation of the syn-Addition Mechanism for Metal-Free Diboration by Using the Crystalline Sponge Method. AB - The stereochemical outcome of the recently developed metal-free 1,2-diboration of aliphatic alkenes has, until now, only been elucidated by indirect means (e.g. derivatization). This is because classical conformational analysis of the resulting 1,2-diboranes is not viable; in the (1)H NMR spectrum the relevant (1)H resonances are broadened by (11)B, and the occurrence of the products as oily compounds precludes X-ray crystallographic analysis. Herein, the crystalline sponge method is used to display the crystal structures of the diboronic esters formed from internal E and Z olefins, evidencing the stereospecific syn addition mechanism of the reaction, which is fully consistent with the prediction from DFT calculations. PMID- 26840198 TI - Corrections. PMID- 26840197 TI - German Society for Immunology and Australasian Society for Immunology joint Workshop 3(rd) -4(th) December 2015 - Meeting report. AB - The German Society for Immunology (DGfI) and the Australasian Society for Immunology (ASI) hosted the first DGfI-ASI joint workshop from December 3-4, 2015 in Canberra, Australia. A delegation of 15 distinguished German immunologists discussed the workshop topic "immune regulation in infections and immune mediated diseases" with the aim to establish new German-Australasian collaborations, discuss new concepts in the field of immune regulation and build a scientific network to create more utilizable resources for excellent (trans-border) immunological research. The workshop was associated with the 45(th) Annual Scientific Meeting of the ASI held from Nov 29-Dec 3, 2015, opening up even more opportunities for finding new collaboration partners. A return meeting will be linked to the annual DGfI meeting that will take place in 2017 in Erlangen. PMID- 26840199 TI - Corrections. PMID- 26840200 TI - Corrections. PMID- 26840204 TI - Repeated weighing during pregnancy is ineffective in minimising maternal weight gain. PMID- 26840206 TI - Toward a new generation of pelvic floor implants with electrospun nanofibrous matrices: A feasibility study. AB - OBJECTIVE: The use of knitted, polypropylene meshes for the surgical treatment of pelvic organ prolapse (POP) is frequently accompanied by severe complications. Looking for alternatives, we studied the potential of three different electrospun matrices in supporting the adhesion, proliferation, and matrix deposition of POP and non-POP fibroblasts, the most important cells to produce extracellular matrix (ECM), in vitro. STUDY DESIGN: We electrospun three commonly used medical materials: nylon; poly (lactide-co-glycolide) blended with poly-caprolactone (PLGA/PCL); and poly-caprolactone blended with gelatin (PCL/Gelatin). The matrices were characterized for their microstructure, hydrophilicity, and mechanical properties. We seeded POP and non-POP fibroblasts from patients with POP and we determined cellular responses and ECM deposition. RESULTS: All matrices had >65% porosity, homogenous microstructures, and close to sufficient tensile strength for pelvic floor repair: 15.4 +/- 3.3 MPa for Nylon; 12.4 +/- 1.6 MPa for PLGA/PCL; and 3.5 +/- 0.9 MPa for PCL/Gelatin. Both the POP and non POP cells adhered to the electrospun matrices; they proliferated well and produced ample ECM. Overall, the best in vitro performance appeared to be on nylon, presumably because this was the most hydrophilic material with the thinnest fibers. CONCLUSION: Electrospun nanofibrous matrices show feasible mechanical strength and great biocompatibility for POP and non-POP fibroblasts to produce their ECM in vitro and, thus, may be candidates for a new generation of implants for pelvic floor repair. Further studies on electrospun nanofibrous matrices should focus on mechanical and immunological conditions that would be presented in vivo. Neurourol. Urodynam. 36:565-573, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26840205 TI - Feeding practices for infants and young children during and after common illness. Evidence from South Asia. AB - Global evidence shows that children's growth deteriorates rapidly during/after illness if foods and feeding practices do not meet the additional nutrient requirements associated with illness/convalescence. To inform policies and programmes, we conducted a review of the literature published from 1990 to 2014 to document how children 0-23 months old are fed during/after common childhood illnesses. The review indicates that infant and young child feeding (IYCF) during common childhood illnesses is far from optimal. When sick, most children continue to be breastfed, but few are breastfed more frequently, as recommended. Restriction/withdrawal of complementary foods during illness is frequent because of children's anorexia (perceived/real), poor awareness of caregivers' about the feeding needs of sick children, traditional beliefs/behaviours and/or suboptimal counselling and support by health workers. As a result, many children are fed lower quantities of complementary foods and/or are fed less frequently when they are sick. Mothers/caregivers often turn to family/community elders and traditional/non-qualified practitioners to seek advice on how to feed their sick children. Thus, traditional beliefs and behaviours guide the use of 'special' feeding practices, foods and diets for sick children. A significant proportion of mothers/caregivers turn to the primary health care system for support but receive little or no advice. Building the knowledge, skills and capacity of community health workers and primary health care practitioners to provide mothers/caregivers with accurate and timely information, counselling and support on IYCF during and after common childhood illnesses, combined with large-scale communication programmes to address traditional beliefs and norms that may be harmful, is an urgent priority to reduce the high burden of child stunting in South Asia. PMID- 26840207 TI - Post-gastric bypass hypoglycaemia: a review. AB - Bariatric surgery is a highly effective treatment for severe obesity, resulting in substantial weight loss and normalizing obesity-related comorbidities. However, long-term consequences can occur, such as postbariatric surgery hypoglycaemia. This is a challenging medical problem, and the number of patients presenting with it has been increasing. Roux-en-Y gastric bypass (RYGB) is the most popular bariatric procedure, and it is the surgery most commonly associated with the development of postbariatric surgery hypoglycaemia. To date, the pathogenesis of this condition has not been completely established. However, various factors - particularly increased postprandial glucagon-like peptide (GLP) 1 secretion - have been considered as crucial mediator. The mechanisms responsible for diabetic remission after bariatric surgery may be responsible for the development of hypoglycaemia, which typically occurs 1-3 h after a meal and is concurrent with inappropriate hyperinsulinaemia. Carbohydrate-rich foods usually provoke hypoglycaemic symptoms, which can typically be alleviated by strict dietary modifications, including carbohydrate restriction and avoidance of high glycaemic index foods and simple sugars. Few patients require further medical intervention, such as medications, but some patients have required a pancreatectomy. Because this option is not always successful, it is no longer routinely recommended. Clinical trials are needed to further determine the pathophysiology of this condition as well as the best diagnostic and treatment approaches for these patients. PMID- 26840208 TI - Assembly of juxtaparanodes in myelinating DRG culture: Differential clustering of the Kv1/Caspr2 complex and scaffolding protein 4.1B. AB - The precise distribution of ion channels at the nodes of Ranvier is essential for the efficient propagation of action potentials along myelinated axons. The voltage-gated potassium channels Kv1.1/1.2 are clustered at the juxtaparanodes in association with the cell adhesion molecules, Caspr2 and TAG-1 and the scaffolding protein 4.1B. In the present study, we set up myelinating cultures of DRG neurons and Schwann cells to look through the formation of juxtaparanodes in vitro. We showed that the Kv1.1/Kv1.2 channels were first enriched at paranodes before being restricted to distal paranodes and juxtaparanodes. In addition, the Kv1 channels displayed an asymmetric expression enriched at the distal juxtaparanodes. Caspr2 was strongly co-localized with Kv1.2 whereas the scaffolding protein 4.1B was preferentially recruited at paranodes while being present at juxtaparanodes too. Kv1.2/Caspr2 but not 4.1B, also transiently accumulated within the nodal region both in myelinated cultures and developing sciatic nerves. Studying cultures and sciatic nerves from 4.1B KO mice, we further showed that 4.1B is required for the proper targeting of Caspr2 early during myelination. Moreover, using adenoviral-mediated expression of Caspr-GFP and photobleaching experiments, we analyzed the stability of paranodal junctions and showed that the lateral stability of paranodal Caspr was not altered in 4.1B KO mice indicating that 4.1B is not required for the assembly and stability of the paranodal junctions. Thus, developing an adapted culture paradigm, we provide new insights into the dynamic and differential distribution of Kv1 channels and associated proteins during myelination. PMID- 26840209 TI - Editorial Comment from Dr Miyata and Dr Sakai to Impact of multimodal treatment on prognosis for patients with metastatic upper urinary tract urothelial cancer: Subanalysis of the multi-institutional nationwide case series study of the Japanese Urological Association. PMID- 26840210 TI - Characterization of in vitro metabolites of irisflorentin by rat liver microsomes using high-performance liquid chromatography coupled with tandem mass spectrometry. AB - Belamcanda chinensis has been extensively used as antibechic, expectorant and anti-inflammatory agent in traditional medicine. Irisflorentin is one of the major active ingredients. However, little is known about the metabolism of irisflorentin so far. In this work, rat liver microsomes (RLMs) were used to investigate the metabolism of this compound for the first time. Seven metabolites were detected. Five of them were identified as 6,7-dihydroxy-5,3',4',5' tetramethoxy isoflavone (M1), irigenin (M2), 5,7,4'-trihydroxy-6,3',5'-trimethoxy isoflavone (M3), 6,7,4'-trihydroxy-5,3',5'-trimethoxy isoflavone (M4) and 6,7,5' trihydroxy-5,3',4'-trimethoxy isoflavone (M5) by means of NMR and/or HPLC-ESI-MS. The structures of M6 and M7 were not elucidated because they produced no MS signals. The predominant metabolite M1 was noted to be a new compound. Interestingly, it was found to possess anticancer activity much higher than the parent compound. The enzymatic kinetic parameters of M1 revealed a sigmoidal profile, with Vmax = 12.02 MUm/mg protein/min, Km = 37.24 MUm, CLint = 0.32 MUL/mg protein/min and h = 1.48, indicating the positive cooperation. For the first time in this work, a new metabolite of irisflorentin was found to demonstrate a much higher biological activity than its parent compound, suggesting a new avenue for the development of drugs from B. chinensis, which was also applicable for other herbal plants. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26840212 TI - Semiconducting Fabrics by In Situ Topochemical Synthesis of Polydiacetylene: A New Dimension to the Use of Organogels. AB - A diyne functionalized 4,6-O-benzylidene beta-d-galactopyranoside gelator, which can align its diyne motifs upon self-assembly (gelation) have been synthesized. The organogel formed by this gelator undergoes topochemical polymerization to polydiacetylene (PDA) under photoirradiation. This strategically designed gelator has been used to make semi-conducting fabrics. By developing the organogel on the fabrics, the gelator molecules were made not only to self-assemble on the fibers, but also to adhere to fabrics through hydrogen bonding. UV irradiation of the gel coated fabric/fiber resulted in the formation of PDA on fibers. The benzylidene motif could be deprotected to get PDA with pendant free sugars that strongly bind to the cotton fibrils through multiple hydrogen bonds. Conductivity measurements revealed the semiconducting nature of these fabrics. PMID- 26840213 TI - Combining Metabolic Engineering and Electrocatalysis: Application to the Production of Polyamides from Sugar. AB - Biorefineries aim to convert biomass into a spectrum of products ranging from biofuels to specialty chemicals. To achieve economically sustainable conversion, it is crucial to streamline the catalytic and downstream processing steps. In this work, a route that combines bio- and electrocatalysis to convert glucose into bio-based unsaturated nylon-6,6 is reported. An engineered strain of Saccharomyces cerevisiae was used as the initial biocatalyst for the conversion of glucose into muconic acid, with the highest reported muconic acid titer of 559.5 mg L(-1) in yeast. Without any separation, muconic acid was further electrocatalytically hydrogenated to 3-hexenedioic acid in 94 % yield despite the presence of biogenic impurities. Bio-based unsaturated nylon-6,6 (unsaturated polyamide-6,6) was finally obtained by polymerization of 3-hexenedioic acid with hexamethylenediamine. PMID- 26840215 TI - Single Lithium-Ion Conducting Polymer Electrolytes Based on a Super-Delocalized Polyanion. AB - A novel single lithium-ion (Li-ion) conducting polymer electrolyte is presented that is composed of the lithium salt of a polyanion, poly[(4 styrenesulfonyl)(trifluoromethyl(S-trifluoromethylsulfonylimino)sulfonyl)imide] (PSsTFSI(-)), and high-molecular-weight poly(ethylene oxide) (PEO). The neat LiPSsTFSI ionomer displays a low glass-transition temperature (44.3 degrees C; that is, strongly plasticizing effect). The complex of LiPSsTFSI/PEO exhibits a high Li-ion transference number (tLi (+) =0.91) and is thermally stable up to 300 degrees C. Meanwhile, it exhibits a Li-ion conductivity as high as 1.35*10(-4) S cm(-1) at 90 degrees C, which is comparable to that for the classic ambipolar LiTFSI/PEO SPEs at the same temperature. These outstanding properties of the LiPSsTFSI/PEO blended polymer electrolyte would make it promising as solid polymer electrolytes for Li batteries. PMID- 26840214 TI - Structurally Defined alphaMHC-II Nanobody-Drug Conjugates: A Therapeutic and Imaging System for B-Cell Lymphoma. AB - Antibody-drug conjugates (ADCs) of defined structure hold great promise for cancer therapies, but further advances are constrained by the complex structures of full-sized antibodies. Camelid-derived single-domain antibody fragments (VHHs or nanobodies) offer a possible solution to this challenge by providing expedited target screening and validation through switching between imaging and therapeutic activities. We used a nanobody (VHH7) specific for murine MHC-II and rendered "sortase-ready" for the introduction of oligoglycine-modified cytotoxic payloads or NIR fluorophores. The VHH7 conjugates outcompeted commercial monoclonal antibodies (mAbs) for internalization and exhibited high specificity and cytotoxicity against A20 murine B-cell lymphoma. Non-invasive NIR imaging with a VHH7-fluorophore conjugate showed rapid tumor targeting on both localized and metastatic lymphoma models. Subsequent treatment with the nanobody-drug conjugate efficiently controlled tumor growth and metastasis without obvious systemic toxicity. PMID- 26840216 TI - Carbocyclic Amino Ketones by Bredt's Rule-Arrested Kulinkovich-de Meijere Reaction. AB - The Ti(II) -mediated formation of cyclopropylamines from alkenes and amides, the Kulinkovich-de Meijere reaction, involves two carbon-carbon bond-forming steps. Strategic use of a tricyclic intermediate can arrest the process if the second step requires formation of a bridgehead double bond. Use of this Bredt's rule constraint results in the production of carbocyclic amino ketones, key alkaloid building blocks. PMID- 26840217 TI - Synthesis and Biological Evaluation of Bromo- and Fluorodanicalipin A. AB - We disclose the syntheses of (+)-bromodanicalipin A as well as (+/-) fluorodanicalipin A. The relative configuration and ground-state conformation in solution of both molecules was secured by J-based configuration analysis which revealed that these are identical to natural danicalipin A. Furthermore, preliminary toxicological investigations suggest that the adverse effect of danicalipin A may be due to the lipophilicity of the halogens. PMID- 26840218 TI - Practical Direct alpha-Arylation of Cyclopentanones by Palladium/Enamine Cooperative Catalysis. AB - Direct arylation of cyclopentanones has been a long-standing challenge because of competitive self-aldol condensation and multiple arylations. Reported herein is a direct mono-alpha-C-H arylation of cyclopentanones with aryl bromides which is enabled by palladium/amine cooperative catalysis. This method is scalable and chemoselective with broad functional-group tolerance. Application to controlled sequential arylation of cyclopentanones has been also demonstrated. PMID- 26840219 TI - A New Method for Re-Analyzing Evaluation Bias: Piecewise Growth Curve Modeling Reveals an Asymmetry in the Evaluation of Pro and Con Arguments. AB - In four studies we tested a new methodological approach to the investigation of evaluation bias. The usage of piecewise growth curve modeling allowed for investigation into the impact of people's attitudes on their persuasiveness ratings of pro- and con-arguments, measured over the whole range of the arguments' polarity from an extreme con to an extreme pro position. Moreover, this method provided the opportunity to test specific hypotheses about the course of the evaluation bias within certain polarity ranges. We conducted two field studies with users of an existing online information portal (Studies 1a and 2a) as participants, and two Internet laboratory studies with mostly student participants (Studies 1b and 2b). In each of these studies we presented pro- and con-arguments, either for the topic of MOOCs (massive open online courses, Studies 1a and 1b) or for the topic of M-learning (mobile learning, Studies 2a and 2b). Our results indicate that using piecewise growth curve models is more appropriate than simpler approaches. An important finding of our studies was an asymmetry of the evaluation bias toward pro- or con-arguments: the evaluation bias appeared over the whole polarity range of pro-arguments and increased with more and more extreme polarity. This clear-cut result pattern appeared only on the pro-argument side. For the con-arguments, in contrast, the evaluation bias did not feature such a systematic picture. PMID- 26840220 TI - Review of the smiliogastrin cyprinids of the Kwilu River (Kasai Basin, central Africa), revised diagnosis for Clypeobarbus (Cyprinidae: Cyprininae: Smiliogastrini) and description of a new species. AB - A revised diagnosis for the smiliogastrin genus Clypeobarbus is provided and a new species, Clypeobarbus breviclipeus, from the Kwilu River (Kasai Basin) of central Africa, is described. Another species co-occurring in the Kwilu system, 'Barbus' matthesi, shares all diagnostic morphological synapomorphies of Clypeobarbus and its generic reassignment is proposed with a taxonomic redescription provided. Nine species are now placed within Clypeobarbus: Clypeobarbus pleuropholis, Clypeobarbus congicus, Clypeobarbus pseudognathodon, Clypeobarbus bomokandi, Clypeobarbus hypsolepis, Clypeobarbus schoutedeni, Clypeobarbus matthesi, Clypeobarbus bellcrossi and Clypeobarbus breviclipeus n. sp. PMID- 26840221 TI - Incidence, characteristics, and treatment outcomes of mycobacterial diseases in transplant recipients. AB - The incidence, clinical characteristics, and treatment outcomes of tuberculosis (TB) and nontuberculous mycobacterial (NTM) disease developed after transplantation (TPL) in transplant recipients were investigated retrospectively. Between 1996 and 2013, 7342 solid-organ transplantation and 1266 hematopoietic stem cell transplantation were performed at a tertiary referral center in South Korea. Among them, TB and NTM disease developed in 130 and 22 patients, respectively. The overall incidence of TB was 257.4 cases/100 000 patient-years (95% confidence interval [CI], 215.1-305.7) and that of NTM disease was 42.7 cases/100 000 patient-years (95% CI, 26.8-64.7). The median interval from organ TPL to the development of mycobacterial disease was 8.5 months (95% CI, 6.3-11.4) in recipients with TB patients and 24.2 months (95% CI, 13.5-55.7) in those with NTM, respectively. Among NTM patients, Mycobacterium avium-intracellulare complex was the most common causative organism, and nodular bronchiectatic type (77.8%) was the most frequent radiologic feature. Favorable treatment outcome was achieved in 83.7% (95% CI, 76.4-89.1) and 68.8% (95% CI, 44.4-85.8) of TB and NTM patients, respectively (P = 0.166). In conclusion, the overall incidence of TB was higher than that of NTM disease in transplant recipients and treatment outcomes were favorable in both drug-susceptible TB and NTM patients. PMID- 26840222 TI - Efficacy and safety of electrochemotherapy combined with peritumoral IL-12 gene electrotransfer of canine mast cell tumours. AB - Electrochemotherapy combined with peritumoral interleukin-12 (IL-12) gene electrotransfer was used for treatment of mast cell tumours in 18 client-owned dogs. Local tumour control, recurrence rate, as well as safety of combined therapy were evaluated. One month after the therapy, no side effects were recorded and good local tumour control was observed with high complete responses rate which even increased during the observation period to 72%. IL-12 gene electrotransfer resulted in 78% of patients with detectable serum IFN-gamma and/or IL-12 levels. In the treated tumours vascular changes as well as minimal T lymphocytes infiltration was observed. After 1 week, the plasmid DNA was not detected intra- or peritumorally and no horizontal gene transfer was observed. In summary, our study demonstrates high antitumour efficacy of electrochemotherapy combined with IL-12 electrotransfer, which also prevented recurrences or distant metastases, as well as its safety and feasibility in treatment of canine mast cell tumours. PMID- 26840223 TI - Expansion of Human Hematopoietic Stem/Progenitor Cells on Decellularized Matrix Scaffolds. AB - Umbilical cord blood (UCB) is one of the richest sources for hematopoietic stem/progenitor cells (HSPCs), with more than 3000 transplantations performed each year for the treatment of leukemia and other bone marrow, immunological, and hereditary diseases. However, transplantation of single cord blood units is mostly restricted to children, due to the limited number of HSPC per unit. This unit develops a method to increase the number of HSPCs in laboratory conditions by using cell-free matrices from bone marrow cells that mimic 'human-body-niche like' conditions as biological scaffolds to support the ex vivo expansion of HSPCs. In this unit, we describe protocols for the isolation and characterization of HSPCs from UCB and their serum-free expansion on decellularized matrices. This method may also help to provide understanding of the biochemical organization of hematopoietic niches and lead to suggestions regarding the design of tissue engineering-based biomimetic scaffolds for HSPC expansion for clinical applications. PMID- 26840224 TI - Derivation of Human Skin Fibroblast Lines for Feeder Cells of Human Embryonic Stem Cells. AB - After the first derivations of human embryonic stem cell (hESC) lines on fetal mouse feeder cell layers, the idea of using human cells instead of mouse cells as feeder cells soon arose. Mouse cells bear a risk of microbial contamination, and nonhuman immunogenic proteins are absorbed from the feeders to hESCs. Human skin fibroblasts can be effectively used as feeder cells for hESCs. The same primary cell line, which can be safely used for up to 15 passages after stock preparations, can be expanded and used for large numbers of hESC derivations and cultures. These cells are relatively easy to handle and maintain. No animal facilities or animal work is needed. Here, we describe the derivation, culture, and cryopreservation procedures for research-grade human skin fibroblast lines. We also describe how to make feeder layers for hESCs using these fibroblasts. PMID- 26840225 TI - Differentiation of Mouse Embryonic Stem Cells into Ventral Foregut Precursors. AB - Anterior definitive endoderm (ADE), the ventral foregut precursor, is both an important embryonic signaling center and a unique multipotent precursor of liver, pancreas, and other organs. Here, a method is described for the differentiation of mouse embryonic stem cells (mESCs) to definitive endoderm with pronounced anterior character. ADE-containing cultures can be produced in vitro by suspension (embryoid body) culture or in a serum-free adherent monolayer culture. ESC-derived ADE cells are committed to endodermal fates and can undergo further differentiation in vitro towards ventral foregut derivatives. PMID- 26840226 TI - Identifying Adult Stem Cells Using Cre-Mediated Lineage Tracing. AB - Lineage-tracing has been used for decades to establish cell fate maps during development. Recently, with the advent of genetic lineage-tracing techniques (employing Cre-lox recombination), it has been possible to permanently mark progenitor/stem cell populations within somatic tissues. In addition, pulse-chase studies have shown that only stem cells are capable of producing labeled progeny after an extensive period of chase. This unit focuses on the protocols used to target putative adult stem cells in vivo. Using these techniques, one should be able to functionally confirm or deny the stem cell capacity of a given cell population. PMID- 26840227 TI - Delivery of Genome Editing Reagents to Hematopoietic Stem/Progenitor Cells. AB - This unit describes the protocol for the delivery of reagents for targeted genome editing to CD34(+) hematopoietic stem/progenitor cells (HSPCs). Specifically, this unit focuses on the process of thawing and pre-stimulating CD34(+) HSPCs, as well as the details of their electroporation with in vitro-transcribed mRNA encoding site-specific nucleases [in this case zinc-finger nucleases (ZFNs)]. In addition, discussed is delivery of a gene editing donor template in the form of an oligonucleotide or integrase-defective lentiviral vector (IDLV). Finally, an analysis of cell survival following treatment and downstream culture conditions are presented. While optimization steps might be needed for each specific application with respect to nuclease and donor template amount, adherence to this protocol will serve as an excellent starting point for this further work. PMID- 26840228 TI - Concise Review: Progress and Challenges in Using Human Stem Cells for Biological and Therapeutics Discovery: Neuropsychiatric Disorders. AB - In facing the daunting challenge of using human embryonic and induced pluripotent stem cells to study complex neural circuit disorders such as schizophrenia, mood and anxiety disorders, and autism spectrum disorders, a 2012 National Institute of Mental Health workshop produced a set of recommendations to advance basic research and engage industry in cell-based studies of neuropsychiatric disorders. This review describes progress in meeting these recommendations, including the development of novel tools, strides in recapitulating relevant cell and tissue types, insights into the genetic basis of these disorders that permit integration of risk-associated gene regulatory networks with cell/circuit phenotypes, and promising findings of patient-control differences using cell-based assays. However, numerous challenges are still being addressed, requiring further technological development, approaches to resolve disease heterogeneity, and collaborative structures for investigators of different disciplines. Additionally, since data obtained so far is on small sample sizes, replication in larger sample sets is needed. A number of individual success stories point to a path forward in developing assays to translate discovery science to therapeutics development. PMID- 26840230 TI - Electrical impedance myography in facioscapulohumeral muscular dystrophy. AB - INTRODUCTION: In this study we determined the reliability and validity of electrical impedance myography (EIM) in facioscapulohumeral muscular dystrophy (FSHD). METHODS: We performed a prospective study of EIM on 16 bilateral limb and trunk muscles in 35 genetically defined and clinically affected FSHD patients (reliability testing on 18 patients). Summary scores based on body region were derived. Reactance and phase (50 and 100 kHz) were compared with measures of strength, FSHD disease severity, and functional outcomes. RESULTS: Participants were mostly men, mean age 53.0 years, and included a full range of severity. Limb and trunk muscles showed good to excellent reliability [intraclass correlation coefficients (ICC) 0.72-0.99]. Summary scores for the arm, leg, and trunk showed excellent reliability (ICC 0.89-0.98). Reactance was the most sensitive EIM parameter to a broad range of FSHD disease metrics. CONCLUSIONS: EIM is a reliable measure of muscle composition in FSHD that offers the possibility to serially evaluate affected muscles. Muscle Nerve 54: 696-701, 2016. PMID- 26840231 TI - Clinical features of acute obstructive suppurative pancreatic ductitis: A retrospective review of 20 cases. AB - BACKGROUND AND AIMS: The clinical features of acute obstructive suppurative pancreatic ductitis (AOSPD) have not been elucidated. We aimed to clarify the clinical features of AOSPD. METHODS: We retrospectively reviewed the clinical features of 20 patients with AOSPD at two tertiary referral centers between 1993 and 2012. We compared 17 AOSPD patients with chronic pancreatitis (CP) and 42 patients with acute-on-CP in terms of clinical characteristics, presentation, and laboratory and imaging findings. RESULTS: The etiology of AOSPD involved CP in 17 (85%) patients, pancreatic ductal adenocarcinoma in 2 (10%), and intraductal papillary mucinous neoplasm in 1 (5%). Endoscopic pancreatic drainage was effective in 19 (95%) patients. Body temperature was significantly higher in AOSPD with CP than acute-on-CP patients (median: 38.2 vs 36.9 degrees C; P < 0.001). Serum amylase levels at onset were significantly lower (median: 133 vs 364.5 U/L; P = 0.009), and C-reactive protein was significantly higher (median: 9.42 vs 1.06 mg/dL; P < 0.001) in AOSPD with CP patients. Enlargement of the pancreatic parenchyma (18 vs 93%; P < 0.001) and stranding of the surrounding fat (12 vs 93%; P < 0.001) on computed tomography were observed less frequently in patients with AOSPD with CP patients. The diameter of the main pancreatic duct was significantly greater in AOSPD with CP than acute-on-CP patients (median: 7 vs 5 mm; P = 0.006). CONCLUSIONS: The major etiology of AOSPD involved CP, and endoscopic pancreatic drainage was effective. The clinical features differ between AOSPD with CP and acute-on-CP. PMID- 26840229 TI - Competitive Mirror Image Phage Display Derived Peptide Modulates Amyloid Beta Aggregation and Toxicity. AB - Alzheimer's disease is the most prominent type of dementia and currently no causative treatment is available. According to recent studies, oligomeric species of the amyloid beta (Abeta) peptide appear to be the most toxic Abeta assemblies. Abeta monomers, however, may be not toxic per se and may even have a neuroprotective role. Here we describe a competitive mirror image phage display procedure that allowed us to identify preferentially Abeta1-42 monomer binding and thereby stabilizing peptides, which destabilize and thereby eliminate toxic oligomer species. One of the peptides, called Mosd1 (monomer specific d-peptide 1), was characterized in more detail. Mosd1 abolished oligomers from a mixture of Abeta1-42 species, reduced Abeta1-42 toxicity in cell culture, and restored the physiological phenotype in neuronal cells stably transfected with the gene coding for human amyloid precursor protein. PMID- 26840232 TI - Two nonspecific lipid transfer proteins (nsLTPs) from tomato seeds are associated to severe symptoms of tomato-allergic patients. AB - SCOPE: Tomato has become one of the most consumed vegetables worldwide, but its intake is often accompanied by an increasing risk of inducing allergic symptoms. The aim of the work was the identification of new seed-specific allergens associated with severe symptoms in patients allergic to this edible vegetable. METHODS AND RESULTS: We used 22 sera from well-defined tomato-allergic patients. Tomato seed proteins were purified and analyzed for biochemical and immunological characterization. A mixture of two associated IgE-binding nsLTPs was purified from tomato seeds. Both allergens, Sola l 7 and Sola l 6, displayed primary structure differences with respect to their counterpart, Sola l 3, from tomato pulp/peel. They retained the ability to bind IgE from 71.4% of patients with severe symptoms. The purified proteins induced positive basophil activation test and skin prick test, and displayed cross-reactivity with homologous allergens from peanut and sunflower seeds, among others. CONCLUSION: We herein described two novel allergens from tomato seeds that belong to the nonspecific lipid transfer protein family classes 1 and 2, respectively. This is the first work associating IgE reactivity to these proteins with severe symptoms of certain tomato-allergic patients. Therefore, they are optimal candidates for clarifying the diagnosis of the tomato allergy. PMID- 26840233 TI - Developing Educators With, From, and About the Technology. PMID- 26840234 TI - Encouraging Specialty Certification: How Multilevel Support Can Help. AB - Professional development through specialty certification is positively associated with nurses' increased confidence in clinical skills, commitment to learning, empowerment, and professional credibility. This translates to improved patient outcomes, with higher organizational reimbursement, in addition to nurse retention and job satisfaction. Despite the call for lifelong learning from the Institute of Medicine, certification rates, especially among nurses in direct patient care, remain low. This article provides a three-tiered approach for organizational leaders and administrators of continuing education programs to establish resources and support for nurses seeking specialty certification. PMID- 26840235 TI - Chemotherapy and Biotherapy: What Nurses Need to Know When Administering to Nononcologic Patients. AB - The use of chemotherapy and biotherapy for nonmalignant conditions is expanding. This has led to the increased educational needs of health care providers that is essential to reducing the risk of exposure to hazardous drugs. PMID- 26840236 TI - Interprofessional Education: Background and Purpose, Part I. AB - Demands are increasing for an interprofessional workforce that can function in team-based care. The goals of interprofessional education and the value proposition surrounding the benefits of interprofessional education are framed. Factors to consider, including subject matter and faculty selection, are presented based on seven features of team performance. PMID- 26840237 TI - Preparing Nurses to Communicate With the Media, Policy Makers, and the Public. AB - Using active learning strategies, educators facilitate nurses' ability to convey messages to nonhealth care audiences about important policy issues. In this article, mock interviews are described as an active learning approach to develop important communication skills for nurses. PMID- 26840238 TI - Qualitative Analysis of the Lived Experience of First-Time Nurse Responders in Disaster. AB - The study purpose was to examine the reflections of the lived experiences of nurses in shelters or temporary community medical clinics responding for the first time to a civilian disaster. The disaster-nursing literature echoes the need for development of disaster content in the nursing curriculum. However, little thematic analysis-supporting curriculum from the lived experience of first time responders exists in the literature. This study's purpose is to identify the essential thematic knowledge and skills necessary to provide care to disaster survivors in communities and for determining the themes necessary to formulate education in emergency preparedness curricula. A narrative inquiry, with a phenomenological analysis, to explore the lived experiences of nurses who responded once to a community disaster was the methodology used to identify themes. Thematic findings demonstrated a lack of prior knowledge about volunteering during a disaster response, that previous mass casualty exercises did not help with their actual responses, and that the participant RNs identified specific and assessment skills necessary for disasters. PMID- 26840239 TI - Multisite Assessment of Nursing Continuing Education Learning Needs Using an Electronic Tool. AB - A continued education needs assessment and associated education plan are required for organizations on the journey for American Nurses Credentialing Center Magnet(r) designation. Leveraging technology to support the assessment and analysis of continuing education needs was a new venture for a 12-hospital regional health system. The purpose of this performance improvement project was to design and conduct an enhanced process to increase the efficiency and effectiveness of gathering data on nurses' preferences and increase nurse satisfaction with the learner assessment portion of the process. Educators trialed the use of a standardized approach via an electronic survey tool to replace the highly variable processes previously used. Educators were able to view graphical summary of responses by category and setting, which substantially decreased analysis and action planning time for education implementation plans at the system, site, or setting level. Based on these findings, specific continuing education action plans were drafted for each category and classification of nurses. PMID- 26840240 TI - Leadership for Transitions of Care: An Active Learning Innovation. AB - Active learning assignments can be achieved in online discussions, resulting in creative linkages for innovation. This article describes how the teaching strategy of active learning assignment evolved into a group of student learners engaging in the development of a creative advanced clinical care scenario in an online graduate core course on leadership and management. The advanced clinical scenario that resulted from the students envisioning the assignment through the continuum of care was innovative and creative. Most importantly, the scenario stimulated vigorous conversation and excitement over the assignment, which promoted learning, pride in accomplishment, and on-the-job impact. This article serves as a model of ways to engage students in active learning for synthesis and evaluation to enable creativity and innovation. PMID- 26840241 TI - Development of an Outcome Measurement Plan for an Accredited Continuing Nursing Education Provider Unit. AB - Continuing nursing education (CNE) programs are designed to contribute to nurses' professional development and to keep current on the latest knowledge and advances in health care. The American Nurses Credentialing Center has begun to focus on the evaluation of outcomes from CNE. This has required changes in the way CNE providers evaluate their program offerings. The creation of an outcome measurement plan for a CNE provider unit produced a method to meet these changes. This article describes the process of developing the plan and discusses several tools to measure outcomes. PMID- 26840242 TI - The Dinakara equation for adjusting DLCO for hemoglobin in the HCT-CI is superior to the Cotes equation for predicting high-risk patients in allogeneic hematopoietic stem cell transplantation. PMID- 26840243 TI - Kruppel-Like Transcription Factor KLF1 Is Required for Optimal gamma- and beta Globin Expression in Human Fetal Erythroblasts. AB - In human adult erythroid cells, lower than normal levels of Kruppel-like transcription factor 1 (KLF1) are generally associated with decreased adult beta- and increased fetal gamma-globin gene expression. KLF1 also regulates BCL11A, a known repressor of adult gamma-globin expression. In seeming contrast to the findings in adult cells, lower amounts of KLF1 correlate with both reduced embryonic and reduced fetal beta-like globin mRNA in mouse embryonic erythroid cells. The role of KLF1 in primary human fetal erythroid cells, which express both gamma- and beta-globin mRNA, is less well understood. Therefore, we studied the role of KLF1 in ex vivo differentiated CD34+ umbilical cord blood cells (UCB erythroblasts), representing the fetal milieu. In UCB erythroblasts, KLF1 binds to the beta-globin locus control region (LCR), and the beta-globin promoter. There is very little KLF1 binding detectable at the gamma-globin promoter. Correspondingly, when cultured fetal UCB erythroblasts are subjected to lentiviral KLF1 knockdown, the active histone mark H3K4me3 and RNA pol II recruitment are diminished at the beta- but not the gamma-globin gene. The amount of KLF1 expression strongly positively correlates with beta-globin mRNA and weakly positively correlates with BCL11A mRNA. With modest KLF1 knockdown, mimicking haploinsufficiency, gamma-globin mRNA is increased in UCB erythroblasts, as is common in adult cells. However, a threshold level of KLF1 is evidently required, or there is no absolute increase in gamma-globin mRNA in UCB erythroblasts. Therefore, the role of KLF1 in gamma-globin regulation in fetal erythroblasts is complex, with both positive and negative facets. Furthermore, in UCB erythroblasts, diminished BCL11A is not sufficient to induce gamma-globin in the absence of KLF1. These findings have implications for the manipulation of BCL11A and/or KLF1 to induce gamma-globin for therapy of the beta hemoglobinopathies. PMID- 26840245 TI - Molecular Simulation Study of Gas Solubility and Diffusion in a Polymer-Boron Nitride Nanotube Composite. AB - We study the possibility of using polymer composites made of a polymer and boron nitride nanotubes (BNNTs) as a new type of membranes for gas separation. The polymer used is amorphous poly(ether imide) (PEI), and zigzag BNNTs are used to generate the composites with the PEI. The solubilities and self-diffusivities of CO2 and CH4 in the PEI and its composites with the BNNTs are calculated by molecular dynamics (MD) simulations. The molecular models of the PEI and its composites with the BNNTs are generated using energy minimization and MD simulation, and the Universal Force Field is used to represent the interactions between all the atoms. The morhology of the composites are characterized and are compared with that of PEI. The accuracy of the computations is tested by calculating the gases' solubilities and self-diffsivities in the pure PEI and comparing them with the experimental data. Good agreement is obtained with the data. The computed diffusivities and solubilities in the polymer-BNNTs composites are much larger than those in the pure polymer, which are attributed to the changes that the BNNTs induce in the polymer composite's free-volume distribution. As the mechanical properties of the polymer-BNNTs composites are superior over those of the pure PEI, their use as a membrane for gas separation offers distinct advantages over the pure polymer. We also demonstrate that, calculating the diffusion coefficients with MD simulations in the NPT ensemble, as opposed to the common practice of utilizing the NVT ensemble, leads to much more accurate results. PMID- 26840244 TI - CRITICAL ANALYSIS OF THE CURRENT TREATMENT GUIDELINES FOR COMPLEX PTSD IN ADULTS. AB - According to current treatment guidelines for Complex PTSD (cPTSD), psychotherapy for adults with cPTSD should start with a "stabilization phase." This phase, focusing on teaching self-regulation strategies, was designed to ensure that an individual would be better able to tolerate trauma-focused treatment. The purpose of this paper is to critically evaluate the research underlying these treatment guidelines for cPTSD, and to specifically address the question as to whether a phase-based approach is needed. As reviewed in this paper, the research supporting the need for phase-based treatment for individuals with cPTSD is methodologically limited. Further, there is no rigorous research to support the views that: (1) a phase-based approach is necessary for positive treatment outcomes for adults with cPTSD, (2) front-line trauma-focused treatments have unacceptable risks or that adults with cPTSD do not respond to them, and (3) adults with cPTSD profit significantly more from trauma-focused treatments when preceded by a stabilization phase. The current treatment guidelines for cPTSD may therefore be too conservative, risking that patients are denied or delayed in receiving conventional evidence-based treatments from which they might profit. PMID- 26840246 TI - New Phytologist: bridging the 'plant function - climate modelling divide'. PMID- 26840247 TI - Introduction to a Virtual Special Issue on plant volatiles. PMID- 26840248 TI - The fate and age of carbon - insights into the storage and remobilization dynamics in trees. PMID- 26840249 TI - Delving in the deep for the origin of plant cell surface proteoglycans. PMID- 26840250 TI - Towards an integrated understanding of terrestrial ecosystem feedbacks to climate change. PMID- 26840252 TI - Why Huddle? Ecological Drivers of Chick Aggregations in Gentoo Penguins, Pygoscelis papua, across Latitudes. AB - Aggregations of young animals are common in a range of endothermic and ectothermic species, yet the adaptive behavior may depend on social circumstance and local conditions. In penguins, many species form aggregations (aka. creches) for a variety of purposes, whilst others have never been observed exhibiting this behavior. Those that do form aggregations do so for three known benefits: 1) reduced thermoregulatory requirements, 2) avoidance of unrelated-adult aggression, and 3) lower predation risk. In gentoo penguins, Pygoscelis papua, chick aggregations are known to form during the post-guard period, yet the cause of these aggregations is poorly understood. Here, for the first time, we study aggregation behavior in gentoo penguins, examining four study sites along a latitudinal gradient using time-lapse cameras to examine the adaptive benefit of aggregations to chicks. Our results support the idea that aggregations of gentoo chicks decrease an individual's energetic expenditure when wet, cold conditions are present. However, we found significant differences in aggregation behavior between the lowest latitude site, Maiviken, South Georgia, and two of the higher latitude sites on the Antarctic Peninsula, suggesting this behavior may be colony specific. We provide strong evidence that more chicks aggregate and a larger number of aggregations occur on South Georgia, while the opposite occurs at Petermann Island in Antarctica. Future studies should evaluate multiple seabird colonies within one species before generalizing behaviors based on one location, and past studies may need to be re-evaluated to determine whether chick aggregation and other behaviors are in fact exhibited species-wide. PMID- 26840251 TI - Food and Nutrient Intake and Nutritional Status of Finnish Vegans and Non Vegetarians. AB - BACKGROUND: Vegetarian and vegan diets have become more popular among adolescents and young adults. However, few studies have investigated the nutritional status of vegans, who may be at risk of nutritional deficiencies. OBJECTIVE: To compare dietary intake and nutritional status of Finnish long-term vegans and non vegetarians. METHODS: Dietary intake and supplement use were estimated using three-day dietary records. Nutritional status was assessed by measuring biomarkers in plasma, serum, and urine samples. Vegans' (n = 22) data was compared with those of sex- and age-matched non-vegetarians (n = 19). RESULTS: All vegans adhered strictly to their diet; however, individual variability was marked in food consumption and supplementation habits. Dietary intakes of key nutrients, vitamins B12 and D, were lower (P < 0.001) in vegans than in non vegetarians. Nutritional biomarker measurements showed lower concentrations of serum 25-hydroxyvitamin D3 (25(OH)D3), iodine and selenium (corrected for multiple comparisons, P < 0.001), Vegans showed more favorable fatty acid profiles (P < 0.001) as well as much higher concentrations of polyphenols such as genistein and daidzein (P < 0.001). Eicosapentaenoic acid proportions in vegans were higher than expected. The median concentration of iodine in urine was below the recommended levels in both groups. CONCLUSIONS: Long-term consumption of a vegan diet was associated with some favorable laboratory measures but also with lowered concentrations of key nutrients compared to reference values. This study highlights the need for nutritional guidance to vegans. PMID- 26840253 TI - The Role of Nitric Oxide and Reactive Oxygen Species in the Killing of Leishmania braziliensis by Monocytes from Patients with Cutaneous Leishmaniasis. AB - Human cutaneous leishmaniasis (CL) caused by Leishmania braziliensis, presents an exaggerated Th1 response that is associated with ulcer development. Macrophages are the primary cells infected by Leishmania parasites and both reactive oxygen species (ROS) and nitric oxide (NO) are important in the control of Leishmania by these cells. The mechanism involved in the killing of L. braziliensis is not well established. In this study, we evaluate the role of ROS and NO in the control of L. braziliensis infection by monocytes from CL patients. After in vitro infection with L. braziliensis, the oxidative burst by monocytes from CL patients was higher when compared to monocytes from healthy subjects (HS). Inhibition of the ROS pathway caused a significant decrease in the oxidative burst in L. braziliensis infected monocytes from both groups. In addition, we evaluated the intracellular expression of ROS and NO in L. braziliensis-infected monocytes. Monocytes from CL patients presented high expression of ROS after infection with L. braziliensis. The expression of NO was higher in monocytes from CL patients as compared to expression in monocytes from HS. A strong positive correlation between NO production and lesion size of CL patients was observed. The inhibition of ROS production in leishmania-infected monocytes from CL patients allowed the growth of viable promastigotes in culture supernatants. Thus, we demonstrate that while production of ROS is involved in L. braziliensis killing, NO alone is not sufficient to control infection and may contribute to the tissue damage observed in human CL. PMID- 26840254 TI - What affects the subjective sleep quality of hospitalized elderly patients? AB - AIM: The present study aimed to identify the factors affecting the subjective sleep quality in elderly inpatients. METHODS: The participants were 290 older adults admitted in three general hospitals. Data were collected using a structured questionnaire consisting of scales for general characteristics, sleep quality, activities of daily living, instrumental activities of daily living and depression. Collected data were analyzed by descriptive statistics, t-test, one way anova, Scheffe post-hoc, Pearson's correlation coefficient and stepwise multiple regression. RESULTS: There were statistically significant differences in sleep quality according to age, education level, marital status, monthly income and number of cohabitants. The most powerful predictor of sleep quality was depression (P < 0.01, R2 = 0.30). Five variables, depression, perceived health status, diagnosis, number of cohabitants and duration of hospitalization; explained 43.0% of the total variance in sleep quality. CONCLUSIONS: Elderly inpatients suffered from low sleep quality, and depression affected their sleep. We should develop and apply hospital-tailored sleep interventions considering older adults' depression, and then hospitalized older adults' sleep could improve. Furthermore, it is useful to identify other sleep-related factors. Geriatr Gerontol Int 2017; 17: 471-479. PMID- 26840255 TI - At least some meiofaunal species are not everywhere. Indication of geographic, ecological and geological barriers affecting the dispersion of species of Ototyphlonemertes (Nemertea, Hoplonemertea). AB - Most meiofaunal species are known to have a broad distribution with no apparent barriers to their dispersion. However, different morphological and/or molecular methods supported patterns of diversity and distribution that may be different among taxa while also conflicting within the same group. We accurately assessed the patterns of geographic distribution in actual genetic species of a marine meiofaunal animal model: Ototyphlonemertes. Specimens were collected from several sites around Europe, Northern and Central America, Southern America, Pacific Islands and Asia. We sequenced regions of two mitochondrial and two nuclear genes. Using single-gene, a concatenated data set, multilocus approaches and different DNA taxonomy methods, we disentangled the actual diversity and the spatial structures of haplotypes and tested the possible correlation between genetic diversity and geographic distance. The results show (i) the importance of using several genes to uncover both diversity and highlight phylogeographic relationships among species and that (ii) independent genetic evolutionary entities have a narrower distribution than morphological species. Moreover, (iii) a Mantel test supported a positive correlation between genetic and geographical distance. By sampling from the two sides of Isthmus of Panama, we were additionally able to identify lineage divergence times that are concordant with vicariance mechanisms caused by the geological closure of the seaway across the Isthmus. We therefore propose that in addition to distance, other geological and ecological conditions are also barriers to the dispersion of and gene flow in marine meiofaunal organisms. PMID- 26840256 TI - Cullin 4A (CUL4A), a direct target of miR-9 and miR-137, promotes gastric cancer proliferation and invasion by regulating the Hippo signaling pathway. AB - Although Cullin 4A (CUL4A) is mutated or amplified in several human cancer types, its role in gastric cancer (GC) and the mechanisms underlying its regulation remain largely uncharacterized. In the present study, we report that the expression of CUL4A significantly correlated with the clinical stage of the tumor and lymph node metastasis, and survival rates were lower in GC patients with higher levels of CUL4A than in patients with lower CUL4A levels. The upregulation of CUL4A promoted GC cell proliferation and epithelial-mesenchymal transition (EMT) by downregulating LATS1-Hippo-YAP signaling. Knocking down CUL4A had the opposite effect in vitro and in vivo. Interestingly, CUL4A expression was inhibited by the microRNAs (miRNAs), miR-9 and miR-137, which directly targeted the 3'-UTR of CUL4A. Overexpression of miR-9 and miR-137 downregulated the CUL4A LATS1-Hippo signaling pathway and suppressed GC cell proliferation and invasion in vitro. Taken together, our findings demonstrate that perturbations to miR 9/137-CUL4A-Hippo signaling contribute to gastric tumorigenesis, and suggest potential therapeutic targets for the future treatment of GC. PMID- 26840257 TI - Antidepressants in association with reducing risk of oral cancer occurrence: a nationwide population-based cohort and nested case-control studies. AB - OBJECTIVES: Several studies suggested that antidepressant use may increase or decrease the risk of cancer occurrence, depending on specific cancer types. The possible carcinogenic effect of antidepressants has received substantial attention; however, evidence remains inconclusive. Here we investigated associations between the use of antidepressants and occurrences of oral cancer (OC). METHODS: Two million samples were randomly collected from the National Health Insurance Research Database in Taiwan, which covers 98% of the total population (23 million). All patients from2000 to 2009 were followed up. We identified 5103 patients newly diagnosed with OC after antidepressants use in addition to 20,412 non-OC matched subjects and 95,452 unmatched non-OC subjects. RESULTS: In nested case control analysis, factors associating with OC, including age [OR = 1.02; 95% confidence interval (CI) = 1.01-1.03) and male (OR = 5.30; 95% CI = 4.92-5.70) were independently associated with increased risk of OC. Based on the functions of antidepressants, antidepressants treatment medications were further classified to investigate risk of OC. Selective serotonin reuptake inhibitors (OR = 0.61; 95% CI = 0.53-0.70) and tricyclic antidepressants (OR = 0.57; 95% CI = 0.52-0.63) were associated with reduced risk of OC. The risk of developing OC among subjects taking antidepressants was less than 26% [hazard ratio (HR) =0.74; 95% CI = 0.68-0.81] in prospective cohort study. The effect of a cumulative duration and dose was a significantly reduced risk of OC. CONCLUSIONS: The association between antidepressant use and decreasing OC risk were demonstrated by both prospective and nested case-control studies. PMID- 26840258 TI - The effect of HMGB1 on the clinicopathological and prognostic features of non small cell lung cancer. AB - Several studies have assessed the diagnostic and prognostic values of high mobility group protein box 1 (HMGB1) expression in non-small cell lung cancer (NSCLC), but these results remain controversial. The purpose of this study was to perform a meta-analysis of the gene microarray analyses of datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to evaluate the association of HMGB1 expression with the clinicopathological and prognostic features of patients with NSCLC. Furthermore, we investigated the underlying molecular mechanisms by bioinformatics analysis. Twenty relevant articles involving 2651 patients were included in this meta-analysis; the HMGB1 expression in NSCLC tissues was significantly higher than that in the healthy non-cancer control tissues. We also found an indication by microarray analysis and meta analysis that HMGB1 expression was associated with the cancer TNM Staging System. In terms of prognostic features, a survival analysis from KM-Plotter tool revealed that the high HMGB1 expression group exhibited poorer survival in lung adenocarcinoma (ADC) and overall NSCLC patients. The survival and disease-free analyses from TCGA datasets also showed that HMGB1 mainly affected the development of patients with ADC. Therefore, we focused on how HMGB1 affected the prognosis and development of ADC using bioinformatics analyses and detected that the mitogen-activated protein kinases (MAPK), apoptosis and cell cycle signaling pathways were the key pathways that varied during HMGB1 up-regulation in ADC. Moreover, various genes such as PLCG2, the phosphatidylinositol-4, 5-bisphosphate 3-kinase superfamily (PI3Ks), protein kinase C (PKC) and DGKZ were selected as hub genes in the gene regulatory network. Our results indicated that HMGB1 is a potential biomarker to predict progression and survival of NSCLC, especially of ADC types. PMID- 26840259 TI - Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment. AB - Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Current research on tumour-related extracellular vesicles (EVs) suggests that exosomes play a significant role in paracrine signaling pathways, thus potentially influencing cancer progression via multiple mechanisms. In fact, during the last decade numerous studies have revealed the role of EVs in the progression of various pathological conditions including cancer. Moreover, differences in the proteomic, lipidomic, and cholesterol content of exosomes derived from PCa cell lines versus benign prostate cell lines confirm that exosomes could be excellent biomarker candidates. As such, as part of an extensive proteomic analysis using LCMS we previously described a potential role of exosomes as biomarkers for PCa. Current evidence suggests that uptake of EV's into the local tumour microenvironment encouraging us to further examine the role of these vesicles in distinct mechanisms involved in the progression of PCa and castration resistant PCa. For the purpose of this study, we hypothesized that exosomes play a pivotal role in cell-cell communication in the local tumour microenvironment, conferring activation of numerous survival mechanisms during PCa progression and development of therapeutic resistance. Our in vitro results demonstrate that PCa derived exosomes significantly reduce apoptosis, increase cancer cell proliferation and induce cell migration in LNCaP and RWPE-1 cells. In conjunction with our in vitro findings, we have also demonstrated that exosomes increased tumor volume and serum PSA levels in vivo when xenograft bearing mice were administered DU145 cell derived exosomes intravenously. This research suggests that, regardless of androgen receptor phenotype, exosomes derived from PCa cells significantly enhance multiple mechanisms that contribute to PCa progression. PMID- 26840261 TI - Aminomethylphosphonic acid inhibits growth and metastasis of human prostate cancer in an orthotopic xenograft mouse model. AB - Aminomethylphosphonic acid (AMPA) has been shown to inhibit prostate cancer cell growth in vitro. The purpose of the present study was to determine if AMPA could inhibit growth and metastasis of prostate cancer in vivo. Human prostate cancer PC-3-LacZ-luciferase cells were implanted into the ventral lateral lobes of the prostate in 39 athymic Nu/Nu nude male mice. Seven days later, mice were randomized into the control group (n = 14, treated intraperitoneally with phosphate buffered saline), low dose group (n = 10, treated intraperitoneally with AMPA at 400 mg/kg body weight/day), and high dose group (n = 15, treated intraperitoneally with AMPA at 800 mg/kg body weight/day). Tumor growth and metastasis were examined every 4-7 days by bioluminescence imaging of live mice. We found that AMPA treatment significantly inhibited growth and metastasis of orthotopic xenograft prostate tumors and prolonged the survival time of the mice. AMPA treatment decreased expression of BIRC2 and activated caspase 3, leading to increased apoptosis in the prostate tumors. AMPA treatment decreased expression of cyclin D1. AMPA treatment also reduced angiogenesis in the prostate tumors. Taken together, these results demonstrate that AMPA can inhibit prostate cancer growth and metastasis, suggesting that AMPA may be developed into a therapeutic agent for the treatment of prostate cancer. PMID- 26840260 TI - CD133 expression may be useful as a prognostic indicator in colorectal cancer, a tool for optimizing therapy and supportive evidence for the cancer stem cell hypothesis: a meta-analysis. AB - We performed a meta-analysis of CD133-related clinical data to investigate the role of cancer stem cells (CSCs) in the clinical outcomes of colorectal cancer (CRC) patients, analyzing the effectiveness of various therapeutic strategies and examining the validity of the CSC hypothesis. For 28 studies (4546 patients), the relative risk (RR) to survival outcomes associated with CD133+ CRCs were calculated using STATA 12.0 software. Pooled results showed that CD133High patients had poor 5-year overall survival (RR 0.713, 95% CI 0.616-0.826) and 5 year disease free survival (RR 0.707, 95% CI 0.602-0.831). Both associations were consistently observed across different races, research techniques and therapeutic strategies. In a subgroup receiving adjuvant therapy, CD133Low patients achieved significantly better survival than CD133High patients. The findings suggest that CD133 could serve as a predictive marker of poor prognosis and treatment failure in CRC. CD133Low patients could benefit from adjuvant treatments, while CD133High patients should be given novel treatments besides adjuvant therapy. Our results also provide evidence in support of the CSC hypothesis. PMID- 26840262 TI - PHOX2B is a suppressor of neuroblastoma metastasis. AB - Paired like homeobox 2B (PHOX2B) is a minimal residual disease (MRD) marker of neuroblastoma. The presence of MRD, also referred to as micro-metastases, is a powerful marker of poor prognosis in neuroblastoma. Lung metastasis is considered a terminal event in neuroblastoma. Lung micro-metastatic neuroblastoma (MicroNB) cells show high expression levels of PHOX2B and possess a less malignant and metastatic phenotype than lung macro metastatic neuroblastoma (MacroNB) cells, which hardly express PHOX2B. In vitro assays showed that PHOX2B knockdown in MicroNB cells did not affect cell viability; however it decreased the migratory capacity of the MicroNB-shPHOX2B cells. An orthotopic inoculation of MicroNB shPHOX2B cells into the adrenal gland of nude mice resulted in significantly larger primary tumors and a heavier micro-metastatic load in the lungs and bone marrow, than when control cells were inoculated. PHOX2B expression was found to be regulated by methylation. The PHOX2B promoter in MacroNB cells is significantly more methylated than in MicroNB cells. Demethylation assays using 5 azacytidine demonstrated that methylation can indeed inhibit PHOX2B transcription in MacroNB cells. These pre-clinical data strongly suggest that PHOX2B functions as a suppressor of neuroblastoma progression. PMID- 26840263 TI - Antimetabolite TTL-315 selectively kills glucose-deprived cancer cells and enhances responses to cytotoxic chemotherapy in preclinical models of cancer. AB - Maintaining thiol homeostasis is an imperative for cancer cell survival in the nutrient-deprived microenvironment of solid tumors. Despite this metabolic vulnerability, a selective approach has yet to be developed to disrupt thiol homeostasis in solid tumors for therapeutic purposes. In this study, we report the identification of 2-mercaptopropionyl glycine disulfide (TTL-315) as a novel antimetabolite that blocks cell survival in a manner conditional on glucose deprivation. In the presence of glucose, TTL-315 lacks cytotoxic effects in normal cells where it is detoxified by reduction to 2-mercaptopropionyl glycine, a compound with known clinical pharmacologic and safety profiles. In several rodent models of aggressive breast, lung and skin cancers, TTL-315 blocked tumor growth and cooperated with the DNA damaging drug cisplatin to trigger tumor regression. Our results offer preclinical proof of concept for TTL-315 as a novel antimetabolite to help selectively eradicate solid tumors by exploiting the glucose-deprived conditions of the tumor microenvironment. PMID- 26840265 TI - Epithelioid hemangioendotheliomas with TFE3 gene translocations are compossible with CAMTA1 gene rearrangements. AB - Epithelioid hemangioendotheliomas (EHEs) are vascular tumors of intermediate malignancy that can undergo high-grade malignant transformations. EHEs have been characterized by tumor-specific WW domain-containing transcription regulator 1(WWTR1)-calmodulin-binding transcription activator 1 (CAMTA1) translocations, and recently, a novel Yes-associated protein 1 (YAP1)-transcription factor E3 (TFE3) gene fusion was identified in EHEs. In this study, we examined the expression levels of TFE3 and CAMTA1 via immunohistochemical staining and identified chromosomal alterations using fluorescence in situ hybridization (FISH) assays and RT-PCR tests. Although all of the EHEs were CAMTA1-positive in immunohistochemical staining, only five out of 18 EHEs (27.78%) positively expressed nuclear TFE3. The five TFE3-positive EHEs exhibited TFE3 gene break apart in FISH assays. YAP1-TFE3 gene fusions were confirmed by RT-PCR. Interestingly, we observed CAMTA1 gene break-apart in all of the five TFE3 positive EHEs via FISH assays, and four out of the five TFE3-positive EHEs exhibited WWTR1-CAMTA1 gene fusions via RT-PCR. These results indicate that these two chromosomal alterations are not mutually exclusive but compossible in EHEs. Finally, primary tumor sites in TFE3-positive EHEs consistently contained single masses (P = 0.0359) with larger sizes (P = 0.0550) compared to TFE3-negative EHEs. Similar to previous reports, we observed well-formed vessels more frequently in TFE3-positive EHEs than in TFE3-negative EHEs (P = 0.0441). In addition, TFE3-positive EHEs tended to more frequently demonstrate high-grade nuclear atypia (P = 0.0654) and hypercellularity (P=0.0987) than TFE3-negative EHEs. Thus, we have now established two clinically distinct subgroups of EHEs: TFE3-positive and TFE3-negative EHEs. PMID- 26840264 TI - Identification of novel plasma glycosylation-associated markers of aging. AB - The pro- or anti-inflammatory activities of immunoglobulins G (IgGs) are controlled by the structure of the glycan N-linked to Asn297 of their heavy chain. The age-associated low grade inflammation (inflammaging) is associated with increased plasmatic levels of agalactosylated IgGs terminating with N acetylglucosamine (IgG-G0) whose biogenesis has not been fully explained. Although the biosynthesis of glycans is in general mediated by glycosyltransferases associated with internal cell membranes, the extracellular glycosylation of circulating glycoproteins mediated by plasmatic glycosyltransferases has been recently demonstrated. In this study we have investigated the relationship between plasmatic glycosyltransferases, IgG glycosylation and inflammatory and aging markers. In cohorts of individuals ranging from infancy to centenarians we determined the activity of plasmatic beta4 galactosyltransferase(s) (B4GALTs) and of alpha2,6-sialyltransferase ST6GAL1, the glycosylation of IgG, the GlycoAge test (a glycosylation-based marker of aging) and the plasma level of inflammatory and liver damage markers. Our results show that: 1) plasmatic B4GALTs activity is a new marker of aging, showing a linear increase throughout the whole age range. 2) plasmatic ST6GAL1 was high only in children and in people above 80, showing a quadratic relationship with age. 3) Neither plasmatic glycosyltransferase correlated with markers of liver damage. 4) plasmatic ST6GAL1 showed a positive association with acute phase proteins in offspring of short lived parents, but not in centenarians or in their offspring. 5) Although the glycosylation of IgGs was not correlated with the level of the two plasmatic glycosyltransferases, it showed progressive age-associated changes consistent with a shift toward a pro-inflammatory glycotype. PMID- 26840267 TI - Pan-cancer analysis of intratumor heterogeneity as a prognostic determinant of survival. AB - As tumors accumulate genetic alterations, an evolutionary process occurs in which genetically distinct subclonal populations of cells co-exist, resulting in intratumor genetic heterogeneity (ITH). The clinical implications of ITH remain poorly defined. Data are limited with respect to whether ITH is an independent determinant of patient survival outcomes, across different cancer types. Here, we report the results of a pan-cancer analysis of over 3300 tumors, showing a varied landscape of ITH across 9 cancer types. While some gene mutations are subclonal, the majority of driver gene mutations are clonal events, present in nearly all cancer cells. Strikingly, high levels of ITH are associated with poorer survival across diverse types of cancer. The adverse impact of high ITH is independent of other clinical, pathologic and molecular factors. High ITH tends to be associated with lower levels of tumor-infiltrating immune cells, but this association is not able to explain the observed survival differences. Together, these data show that ITH is a prognostic marker in multiple cancers. These results illuminate the natural history of cancer evolution, indicating that tumor heterogeneity represents a significant obstacle to cancer control. PMID- 26840269 TI - Analysis of Effectiveness of Different Rotational Instruments in Implantoplasty: An In Vitro Study. AB - OBJECTIVE: To analyze the temperature increase in the implant, adjacent bone, procedure time, and roughness provided by different rotatory instruments in the implantoplasty procedure. MATERIAL AND METHODS: Three types of rotational instruments were used to evaluate the implant surface wear, divided according to their surface features: Group 1 (G1) diamond, Group 2 (G2) tungsten carbide, and Group 3 (G3) multilaminar. For the roughness test, a control group was included for comparison with the test groups. RESULTS: The temperature variation was statistically significant in the implant (P < 0.05) where G2 showed the lowest variation. There was no statistically significant difference between the 3 groups regarding the temperature increase measured in the bone (P > 0.05). The difference of wear time was statistically significant (P < 0.05) with faster results for G3. In the surface roughness analyses, there was a statistically significant difference (P < 0.05) between the control group and the test groups. Among the 3 test groups, the difference between measurements was not statistically significant (P > 0.05). CONCLUSION: All tested rotatory instruments performed the same level of surface roughness in the implantoplasty. The tungsten carbide bur caused a minor change in the implant temperature. The multilaminar bur performed a faster wear time. More in vivo studies are necessary to conclude which is the best rotatory instrument for implantoplasty. PMID- 26840266 TI - JNK pathway inhibition selectively primes pancreatic cancer stem cells to TRAIL induced apoptosis without affecting the physiology of normal tissue resident stem cells. AB - OBJECTIVE: Successful treatment of solid cancers mandates targeting cancer stem cells (CSC) without impact on the physiology of normal tissue resident stem cells. C-Jun N-terminal kinase (JNK) signaling has been shown to be of importance in cancer. We test whether JNK inhibition would sensitize pancreatic CSCs to induction of apoptosis via low-dose TNFalpha-related apoptosis-inducing ligand (TRAIL). DESIGN: Effects of JNK inhibition (JNKi) were evaluated in vitro in functional assays, through mRNA and protein expression analysis, and in in vivo mouse studies. CSCs were enriched in anoikis-resistant spheroid culture and analyzed accordingly. RESULTS: We confirmed that the JNK pathway is an important regulatory pathway in pancreatic cancer stem cells and further found that JNK inhibition downregulates the decoy receptor DcR1 through IL-8 signaling while upregulating pro-apoptotic death receptors DR4/5, thereby sensitizing cells - even with acquired TRAIL-resistance - to apoptosis induction. Treatment of orthotopic pancreatic cancer xenografts with either gemcitabine, JNKi or TRAIL alone for 4 weeks showed only modest effects compared to control, while the combination of JNKi and TRAIL resulted in significantly lower tumor burden (69%; p < 0.04), reduced numbers of circulating tumor cells, and less distant metastatic events, without affecting the general health of the animals. CONCLUSIONS: The combination of JNKi and TRAIL significantly impacts on CSCs, but leaves regular tissue-resident stem cells unaffected - even under hypoxic stress conditions. This concept of selective treatment of pancreatic CSCs warrants further evaluation. PMID- 26840268 TI - Development of a metabolites risk score for one-year mortality risk prediction in pancreatic adenocarcinoma patients. AB - PURPOSE: Survival among patients with adenocarcinoma pancreatic cancer (PDCA) is highly variable, which ranges from 0% to 20% at 5 years. Such a wide range is due to tumor size and stage, as well other patients' characteristics. We analyzed alterations in the metabolomic profile, of PDCA patients, which are potentially predictive of patient's one-year mortality. EXPERIMENTAL DESIGN: A targeted metabolomic assay was conducted on serum samples of patients diagnosed with pancreatic cancer. Statistical analyses were performed only for those 27 patients with information on vital status at follow-up and baseline clinical features. Random Forest analysis was performed to identify all metabolites and clinical variables with the best capability to predict patient's mortality risk at one year. Regression coefficients were estimated from multivariable Weibull survival model, which included the most associated metabolites. Such coefficients were used as weights to build a metabolite risk score (MRS) which ranged from 0 (lowest mortality risk) to 1 (highest mortality risk). The stability of these weights were evaluated performing 10,000 bootstrap resamplings. RESULTS: MRS was built as a weighted linear combination of the following five metabolites: Valine (HR = 0.62, 95%CI: 0.11-1.71 for each standard deviation (SD) of 98.57), Sphingomyeline C24:1 (HR = 2.66, 95%CI: 1.30-21.09, for each SD of 20.67), Lysine (HR = 0.36, 95%CI: 0.03-0.77, for each SD of 51.73), Tripentadecanoate TG15 (HR = 0.25, 95%CI: 0.01-0.82, for each SD of 2.88) and Symmetric dimethylarginine (HR = 2.24, 95%CI: 1.28-103.08, for each SD of 0.62), achieving a very high discrimination ability (survival c-statistic of 0.855, 95%CI: 0.816-0.894). Such association was still present even after adjusting for the most associated clinical variables (confounders). CONCLUSIONS: The mass spectrometry-based metabolomic profiling of serum represents a valid tool for discovering novel candidate biomarkers with prognostic ability to predict one-year mortality risk in patients with pancreatic adenocarcinoma. PMID- 26840270 TI - Success Rate of Two-Piece Zirconia Implants: A Retrospective Statistical Analysis. AB - PURPOSE: About 10 years ago, one-piece zirconia implants were introduced to dentistry. The aim of the study was to evaluate the clinical success of two-piece zirconia implants regarding osseointegration using the manufacturers' warranty data. MATERIALS AND METHODS: Over a period of 4 years (2010-2014), the data of warranty replacements of 15,255 sold Zeramex implants were evaluated retrospectively and blinded. RESULTS: Three hundred forty-seven (2.2%) nonosseointegrated implants were sent back. Zeramex T showed an average success rate of 96.7%, whereas Zeralock implants exhibited an average success rate of 98.5%. Furthermore, Zeramex Plus implants exhibit an average success rate of 99.4% within the investigated period. Assuming, that 2% of the failed implants were unreturned, the above-mentioned values show no changes. Assuming 5% (10%) of unreturned nonosseointegrated implants, the average success rate of Zeramex T decreases from 96.7% to 96.6% (96.4%) and of Zeralock from 98.5% to 98.4% (98.4%), respectively. The success rate of Zeramex Plus implants remains unchanged at 99.4%. CONCLUSION: The results of this study imply that two-piece zirconia implants show competitive success rates, improved from >96.7% to >98.5% over three product generations. PMID- 26840271 TI - Soft Tissue Augmentation Techniques and Materials Used in the Oral Cavity: An Overview. AB - PURPOSE: Oral soft tissue augmentation or grafting procedures are often necessary to achieve proper wound closure after deficits resulting from tumor excision, clefts, trauma, dental implants, and tooth recessions. MATERIALS AND METHODS: Autologous soft tissue grafts still remain the gold standard to acquire a functionally adequate zone of keratinized attached gingiva. However, soft tissue substitutes are more commonly used because they minimize morbidity and shorten surgical time. RESULTS: This review aimed to assess soft tissue grafting techniques and materials used in the oral cavity from existing literature. There are a large variety of materials and techniques, including grafts, local flaps, allogenic derived matrices such as acellular dermal allograft, xenogenic tissue matrices from animal origin, and synthetic materials. CONCLUSIONS: Tissue engineering of oral mucosa represents an interesting alternative to obtain sufficient autologous tissue for reconstructing oral wounds using biodegradable scaffolds, and may improve vascularization and epithelialization, which are critical for successful outcomes. PMID- 26840272 TI - Conservative Management of Minimally Displaced (<=2 mm) Fractures of the Lateral Humeral Condyle in Pediatric Patients: A Systematic Review. AB - BACKGROUND: Fractures to the lateral humeral condyle are common in the pediatric population and can lead to complications related to displacement of the fracture fragment. The ideal treatment for minimally displaced fractures (measuring <=2 mm) is controversial. METHODS: A systematic review was performed identifying and evaluating studies related to displacement of lateral humeral condyle fractures in pediatric patients. Databases included in this review were PubMed, Biosis Preview, SPORTDiscus, PEDro, and EMBASE. We investigated the rate of subsequent displacement for minimally displaced fractures following immobilization, the time span in which fracture displacement occurs, and the complications related to displacement despite immobilization. RESULTS: Our review of the literature found 6 studies that matched the search criteria. The risk of subsequent displacement in minimally displaced fractures initially treated with immobilization was 14.9% with fracture displacement typically occurring within the first week following injury. Malunion, nonunion, and loss of motion were the most commonly identified complications following subsequent displacement. CONCLUSIONS: For minimally displaced fractures of the lateral humeral condyle, appropriate diagnosis of fracture stability and fracture displacement with close radiographic follow-up 1 week following injury dictate the success of conservative management. LEVEL OF EVIDENCE: Level II-systematic review of level-II or level-I studies with inconsistent results. PMID- 26840273 TI - Local Infiltration Analgesia Compared With Epidural and Intravenous PCA After Surgical Hip Dislocation for the Treatment of Femoroacetabular Impingement in Adolescents. AB - BACKGROUND: Open treatment of femoroacetabular impingement (FAI) through a surgical hip dislocation (SHD) approach has been reported to allow for improvement in pain and function. However, the approach require a trochanteric osteotomy and may be associated with high level of pain after surgery. Currently, there is no systematic approach for pain management after SHD for treatment of FAI. METHODS: A retrospective chart review was used to collect data from 121 subjects (12 to 21 y and below) who received periarticular local infiltration analgesia (LIA, n=20), epidural analgesia (n=72), or intravenous patient controlled analgesia (PCA, n=29) after SHD from January 2003 to June 2014. Verbal pain scores, opioid consumption, incidence of side effects/complications, and length of hospital stay (LOS) were recorded. All nonopioid medications with analgesic potential were included in the statistical models as potential confounding variables RESULTS:: Twelve hours after surgery, the odds of moderate/severe pain were higher in the PCA group (odds ratio, 20.5; 95% confidence interval (CI), 1.7-243.8; P=0.0166] and epidural group (odds ratio, 5.2; 95% CI, 0.7-92.0; P=0.3218) compared with the LIA group. There was no difference in pain scores across all groups 1 hour (P=0.0675) or 24 hours (P=0.3473) postoperatively. Total opioid consumption in the LIA group was 59.8% (95% CI, 15.0%-81.0%; P=0.0175) lower than the total opioid consumption in the epidural group and 60.7% (95% CI, 17.3-81.3; P=0.0144) lower than the total opioid consumption in the PCA group. LOS was increased in the epidural (mean difference, 22.1; 95% CI, 6.8-37.4 h; P=0.0051) and PCA (mean difference, 16 h; 95% CI, 1-31.5 h; P=0.0367) groups relative to the LIA group. There was 0 (0%) complication in the LIA group compared with 11 (15.3%) in the epidural group. CONCLUSIONS: LIA was more effective at controlling pain 12 hours after surgery in comparison with PCA with similar pain control to epidural. LIA was associated with significantly lower need for opioids and shorter LOS compared with the PCA and epidural protocols. Periarticular infiltration should be considered for pain management after SHD for treatment of FAI in adolescents. LEVEL OF EVIDENCE: Level III-retrospective comparative study. PMID- 26840274 TI - Functional Outcome of Forearm Rodding in Children With Osteogenesis Imperfecta. AB - BACKGROUND: The impact of corrective forearm surgery on functional ability in children with osteogenesis imperfecta (OI) has not previously been reported. This study addresses this issue. METHODS: A retrospective chart review was conducted on 19 children with OI who underwent 22 corrective forearm procedures between 1996 and 2013. Functional ability was assessed preoperatively and every year postoperatively using the Pediatric Evaluation of Disability Inventory (PEDI). RESULTS: The mean PEDI self-care score increased by 6.8 (P=0.017) and the mean PEDI mobility score increased by 7.2 (P=0.020) at 1-year postsurgery. Functional gains were greater in moderate OI (types IV, V, and VI) than in severe OI (type III). Improved function was maintained in the majority of cases at a mean of 8.9 years postcorrection. CONCLUSIONS: Corrective forearm surgery in children with OI leads to improved functional ability. LEVEL OF EVIDENCE: Level IV. PMID- 26840275 TI - Intraobserver and Interobserver Reliability of the Oberg-Manske-Tonkin (OMT) Classification: Establishing a Registry on Congenital Upper Limb Differences. AB - BACKGROUND: The purpose of this investigation was to determine the reliability of the Oberg-Manske-Tonkin (OMT) classification system applied to patients enrolled in a prospective, multicenter cohort study of congenital upper limb differences. Our hypothesis was that the OMT classification would exhibit high intraobserver and interobserver reliability and thus would be an appropriate tool for the new Congenital Upper Limb Differences registry. METHODS: Four pediatric hand surgeons independently reviewed the medical records, clinical photographs, and radiographs of 60 randomly selected patients previously enrolled in the Congenital Upper Limb Differences registry. Patient's information was summarized and shared electronically (PowerPoint). Each rater classified each congenital anomaly according to the OMT classification system. Responses were recorded using a web based data capture tool (REDCap). Three weeks later, the surgeons repeated the process. Intraobserver reliability for each rater was assessed using Fleiss' kappa. Interobserver reliability was assessed using percent exact agreement (when all 4 raters were in agreement) as well as Fleiss' kappa. RESULTS: Using the OMT classification, intraobserver reliability for the 4 pediatric hand surgeons showed almost perfect agreement, with kappa values in the range of 0.89 to 0.93. Interobserver reliability demonstrated substantial agreement, with kappa value of 0.79 (95% confidence interval, 0.77-0.82) in the first reading and 0.80 (95% confidence interval, 0.77-0.83) in the second reading. The highest possible agreement (kappa=1) was seen for the following diagnoses: congenital dislocation of radial head (OMT I.A.2.v), Madelung deformity (I.A.2.vii), radial polydactyly (I.B.2.iii), triphalangeal thumb (I.B.2.iv), Kirner deformity (I.B.4.vi), and osteochondromatosis (3.B.4.i). CONCLUSIONS: The OMT classification of congenital upper limb differences exhibits substantial to almost perfect intraobserver and interobserver reliability among pediatric hand surgeons at different institutions. The OMT is therefore well-suited for classification of congenital upper limb anomalies in patients enrolled in a multicenter registry. LEVEL OF EVIDENCE: Level II-diagnostic. PMID- 26840276 TI - Beneficial Effect of a Resorbable Biliary Stent in Living Donor Liver Transplantation. AB - BACKGROUND: Living donor liver transplantation (LDLT) entails a significant number of bile duct complications. We aimed to diminish the biliary complication rate with the use of a resorbable biliary stent (RBS) during LDLT. The objective of this study is to describe the surgical techniques and the associated outcomes, especially in terms of safety, of RBS use in LDLT. METHODS: From 2011 to 2014, 12 LDLT recipients were enrolled in a clinical trial with the use of a specifically designed RBS. These patients were followed according to the clinical protocol. Specific complications derived from RBS as well as biliary complications were recorded. RESULTS: One patient underwent early retransplantation due to a small for-size syndrome. None of the patients had a complication attributable to the placement, remaining in place, or degradation of the stent. Four of the remaining patients presented with a biliary complication: 1 (9.1%) with a biliary leak alone, 1 (9.1%) with a biliary stenosis alone, and 2 (18.2%) with both. However, none of the leaks could be directly attributed to the RBS. Patient and graft 1 year survival was 100 and 91.7%, respectively. CONCLUSION: The use of an RBS in LDLT is not associated with complications, and initial results regarding efficacy and safety are encouraging. The need for a larger and prospective study is warranted. PMID- 26840277 TI - Polymersomes via Self-Assembly of Amphiphilic beta-Cyclodextrin-Centered Triarm Star Polymers for Enhanced Oral Bioavailability of Water-Soluble Chemotherapeutics. AB - To date, improving oral bioavailability of water-soluble drugs with poor membrane permeability is still challenging. An example of this includes doxorubicin hydrochloride (DOX.HCl), a widely used chemotherapeutic. We therefore developed a novel DOX.HCl-loaded polymersome (Ps-DOX.HCl) self-assembled by amphiphilic beta cyclodextrin-centered triarm star polymer (mPEG(2k)-PLA(3k))3-CD with the considerable drug loading capability. Using Madin-Darby canine kidney (MDCK) cells trans-well models, it was found that the cellular uptake and absorptive transport of DOX.HCl was significantly increased and the efflux was attenuated when delivered through polymersomes than free drugs. This phenomenon was further verified in mechanistic studies, which was attributed to the change in membrane transport pathway from paracellular route (free DOX.HCl) to active transcellular transport (drug-loaded polymersomes). Moreover, in vivo pharmacokinetic studies in mice demonstrated a significant increase in the oral bioavailability of Ps DOX.HCl compared with free DOX.HCl (7.32-fold), as well as extended half-life (8.22-fold). This resulted in a substantial anticancer efficacy against mouse sarcoma 180 (S180) tumor in vivo. The cardiotoxicity, which is intrinsically induced by DOX.HCl, and toxicity toward gastrointestinal tissues were avoided according to histological studies. These findings indicate that (mPEG(2k) PLA(3k))3-CD copolymer displays great potential as a vehicle for the effective oral delivery of water-soluble drugs with low permeability. PMID- 26840278 TI - Methane Isotope Instrument Validation and Source Identification at Four Corners, New Mexico, United States. AB - Measurements of delta(13)CH4 and CH4 concentration were made at a field site in Four Corners, New Mexico (FC), where we observed large sustained CH4 enhancements (2-8 ppm peaks for hours) during nocturnal inversions. Potential sources of this large CH4 signal at FC include (1) fugitive emissions from coal mining and gas processing that are thermogenic and isotopically (13)C enriched relative to background atmosphere and (2) emissions from agriculture, ruminants, landfills, and coalbed biogenic methane that are(13)C depleted relative to background atmosphere. We analyze our measurements of methane concentration and delta(13)C during spring and summer of 2012 to identify fugitive methane sources. We find CH4 plumes that are both enriched and depleted in (13)C relative to CH4 in background air. Keeling plots show a continuum of delta(13)C source compositions between -400/00 and -600/00 that are consistent with thermogenic and biogenic sources. The Picarro Mobile Methane Investigator (PMMI), a mobile delta(13)CH4 instrument platform, was deployed in the spring of 2013 and used to verify the isotopic enrichment of coal bed methane in the region. We combine our results with meteorological data to spatially separate these sources in the Four Corners regions. Using CO and CO2 data, along with meteorological data, we propose that the high methane concentration events ([CH4] > 3.5 ppm) are from both thermogenic and biogenic methane released from coal beds. PMID- 26840279 TI - Utilization of Cyanoacetohydrazide and Oxadiazolyl Acetonitrile in the Synthesis of Some New Cytotoxic Heterocyclic Compounds. AB - A (pyridazinyl)acetate derivative was reacted with thiosemicarbazide and hydrazine hydrate to yield spiropyridazinone and acetohydrazide derivatives, respectively. The acetohydrazide derivative was used as a starting material for synthesizing some new heterocyclic compounds such as oxoindolinylidene, dimethylpyrazolyl, methylpyrazolyl, oxopyrazolyl, cyanoacetylacetohydrazide and oxadiazolylacetonitrile derivatives. The behavior of the cyanoacetylacetohydrazide and oxadiazolylacetonitrile derivatives towards nitrogen and carbon nucleophiles was investigated. The assigned structures of the prepared compounds were elucidated by spectral methods (IR, 1H-NMR (13)C-NMR and mass spectroscopy). Some of the newly prepared compounds were tested in vitro against a panel of four human tumor cell lines, namely hepatocellular carcinoma (liver) HePG-2, colon cancer HCT-116, human prostate cancer PC3, and mammary gland breast MCF-7. Also they were tested as antioxidants. Almost all of the tested compounds showed satisfactory activity. PMID- 26840280 TI - Tomato Aqueous Extract Modulates the Inflammatory Profile of Immune Cells and Endothelial Cells. AB - Nutrients transiently or chronically modulate functional and biochemical characteristics of cells and tissues both in vivo and in vitro. The influence of tomato aqueous extract (TAE) on the in vitro inflammatory response of activated human peripheral blood leukocytes (PBLs) and macrophages was investigated. Its effect on endothelial dysfunction (ED) was analyzed in human umbilical vein endothelial cells (HUVECs). Murine macrophages (RAW264.7 cells), PBLs and HUVECs were incubated with TAE. They were activated with LPS or TNF-alpha in order to induce inflammatory processes and ED, respectively. Inflammatory mediators and adhesion molecules were measured by immune assay-based multiplex analysis. Gene expression was quantified by RT-PCR. TAE altered the production of interleukins (IL-1beta, IL-6, IL-10, IL-12) and chemokines (CCL2/MCP-1, CCL3/MIP-1alpha, CCL5/RANTES, CXCL8/IL-8, CXCL10/IP-10) in PBLs. TAE reduced ED-associated expression of adhesion molecules (ICAM-1, VCAM-1) in endothelial cell. In macrophages, the production of nitric oxide, PGE2, cytokines and ILs (TNF-alpha, IL-1beta, IL-6, IL-12), which reflects chronic inflammatory processes, was reduced. Adenosine was identified as the main bioactive of TAE. Thus, TAE had cell-specific and context-dependent effects. We infer from these in vitro data, that during acute inflammation TAE enhances cellular alertness and therefore the sensing of disturbed immune homeostasis in the vascular-endothelial compartment. Conversely, it blunts inflammatory mediators in macrophages during chronic inflammation. A novel concept of immune regulation by this extract is proposed. PMID- 26840282 TI - A Sustainable Approach to the Stereoselective Synthesis of Diazaheptacyclic Cage Systems Based on a Multicomponent Strategy in an Ionic Liquid. AB - The microwave-assisted three-component reactions of 3,5-bis(E) arylmethylidene]tetrahydro-4(1H)-pyridinones, acenaphthenequinone and cyclic alpha-amino acids in an ionic liquid, 1-butyl-3-methylimidazolium bromide, occurred through a domino sequence affording structurally intriguing diazaheptacyclic cage-like compounds in excellent yields. PMID- 26840281 TI - Olive Oil and the Hallmarks of Aging. AB - Aging is a multifactorial and tissue-specific process involving diverse alterations regarded as the "hallmarks of aging", which include genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion and altered intracellular communication. Virtually all these hallmarks are targeted by dietary olive oil, particularly by virgin olive oil, since many of its beneficial effects can be accounted not only for the monounsaturated nature of its predominant fatty acid (oleic acid), but also for the bioactivity of its minor compounds, which can act on cells though both direct and indirect mechanisms due to their ability to modulate gene expression. Among the minor constituents of virgin olive oil, secoiridoids stand out for their capacity to modulate many pathways that are relevant for the aging process. Attenuation of aging-related alterations by olive oil or its minor compounds has been observed in cellular, animal and human models. How olive oil targets the hallmarks of aging could explain the improvement of health, reduced risk of aging associated diseases, and increased longevity which have been associated with consumption of a typical Mediterranean diet containing this edible oil as the predominant fat source. PMID- 26840284 TI - Synthesis and Characterization of Macrocyclic Polyether N,N'-Diallyl-7,16-diaza 1,4,10,13-tetraoxa-dibenzo-18-crown-6. AB - In this study an efficient and direct production procedure for a macrocyclic polyether N,N'-diallyl-7,16-diaza-1,4,10,13-tetraoxa-dibenzo-18-crown-6 from the reaction of catechol and N,N-bis(2-chloroethyl)prop-2-en-1-amine in n-butanol in the presence of a strong base is reported. The synthesis involves a two-step addition of sodium hydroxide to enhance the cyclization process, and at the end of the reaction, the reaction mixture is neutralized and the solvent replaced with water in-situ through distillation to afford a relatively pure precipitate that is easily recrystallized from acetone. The yield of the macrocycle was 36% 45% and could be scaled-up to one-mole quantities. The structure and purity of this compound was verified on the basis of elemental analysis, IR, UV-Vis, 1H-, (13)C-NMR, 2D-NMR, mass spectroscopy, and thermal analysis. The white crystalline compound has a sharp melting point of 124 degrees C and a crystallization temperature of 81.4 degrees C determined by differential scanning calorimetry. Our motivation behind the synthesis of the bibracchial lariat azacrown polyether ligand was to examine its possible applications in ion-selective polymer supported materials. PMID- 26840283 TI - Insight of Saffron Proteome by Gel-Electrophoresis. AB - Saffron is a spice comprised of the dried stigmas and styles of Crocus sativus L. flowers and, since it is very expensive, it is frequently adulterated. So far, proteomic tools have never been applied to characterize the proteome of saffron or identify possible cases of fraud. In this study, 1D-Gel Electrophoresis was carried out to characterize the protein profile of (i) fresh stigmas and styles of the plant; (ii) dried stigmas and styles from different geographical origins (Spanish, Italian, Greek and Iranian) that had been stored for various periods of time after their processing; and (iii) two common plant adulterants, dried petals of Carthamus tinctorius L. and dried fruits of Gardenia jasminoides Ellis. A selective protein extraction protocol was applied to avoid interference from colored saffron metabolites, such as crocins, during electrophoretic analyses of saffron. We succeeded in separating and assigning the molecular weights to more than 20 proteins. In spite of the unavailability of the genome of saffron, we were able to identify five proteins by Peptide Mass Fingerprinting: phosphoenolpyruvate carboxylase 3, heat shock cognate 70 KDa protein, crocetin glucosyltransferase 2, alpha-1,4-glucan-protein synthase and glyceraldehydes-3 phosphate dehydrogenase-2. Our findings indicate that (i) few bands are present in all saffron samples independently of origin and storage time, with amounts that significantly vary among samples and (ii) aging during saffron storage is associated with a reduction in the number of detectable bands, suggesting that proteases are still active. The protein pattern of saffron was quite distinct from those of two common adulterants, such as the dried petals of Carthamus tinctorius and the dried fruits of Gardenia jasminoides indicating that proteomic analyses could be exploited for detecting possible frauds. PMID- 26840285 TI - A SILAC-Based Approach Elicits the Proteomic Responses to Vancomycin-Associated Nephrotoxicity in Human Proximal Tubule Epithelial HK-2 Cells. AB - Vancomycin, a widely used antibiotic, often induces nephrotoxicity, however, the molecular targets and underlying mechanisms of this side effect remain unclear. The present study aimed to examine molecular interactome and analyze the signaling pathways related to the vancomycin-induced nephrotoxicity in human proximal tubule epithelial HK-2 cells using the stable isotope labeling by amino acids in cell culture (SILAC) approach. The quantitative proteomic study revealed that there were at least 492 proteins interacting with vancomycin and there were 290 signaling pathways and cellular functions potentially regulated by vancomycin in HK-2 cells. These proteins and pathways played a critical role in the regulation of cell cycle, apoptosis, autophagy, EMT, and ROS generation. These findings suggest that vancomycin-induced proteomic responses in HK-2 cells involvefunctional proteins and pathways that regulate cell cycle, apoptosis, autophagy, and redox homeostasis. This is the first systemic study revealed the networks of signaling pathways and proteomic responses to vancomycin treatment in HK-2 cells, and the data may be used to discriminate the molecular and clinical subtypes and to identify new targets and biomarkers for vancomycin-induced nephrotoxic effect. Further studies are warranted to explore the potential of quantitative proteomic analysis in the identification of new targets and biomarkers for drug-induced renal toxicity. PMID- 26840286 TI - Synthesis and Characterization of Novel Polythiophenes Containing Pyrene Chromophores: Thermal, Optical and Electrochemical Properties. AB - A novel series of pyrene containing thiophene monomers TPM1-5 were synthesized and fully characterized by FTIR, MS, 1H- and (13)C-NMR spectroscopy; their thermal properties were determined by TGA and DSC. These monomers were chemically polymerized using FeCl3 as oxidizing agent to give the corresponding oligomers TPO1-5) and they were electrochemically polymerized to obtain the corresponding polymer films deposited onto ITO. All oligomers exhibited good thermal stability, with T10 values between 255 and 299 degrees C, and Tg values varying from 36 to 39 degrees C. The monomers showed an absorption band at 345 nm due to the S0 -> S2 transition of the pyrene group, whereas the fluorescence spectra showed a broad emission band arising from the "monomer" emission at 375-420 nm. The obtained polymers exhibited two absorption bands at 244 and 354 nm, due to the polythiophene and the pyrene moieties, respectively. The fluorescence spectra of polymers showed a broad "monomer" emission at 380-420 nm followed by an intense excimer emission band at 570 nm, due to the presence of intramolecular pyrene pyrene interactions in these compounds. PMID- 26840287 TI - Synthesis of the Fatty Esters of Solketal and Glycerol-Formal: Biobased Specialty Chemicals. AB - The caprylic, lauric, palmitic and stearic esters of solketal and glycerol formal were synthesized with high selectivity and in good yields by a solvent-free acid catalyzed procedure. No acetal hydrolysis was observed, notwithstanding the acidic reaction conditions. PMID- 26840288 TI - Inhibitory Effect of Rosa rugosa Tea Extract on the Formation of Heterocyclic Amines in Meat Patties at Different Temperatures. AB - In previous studies, heterocyclic amines (HCAs) have been identified as carcinogenic and a risk factor for human cancer. Therefore, the present study was designed to identify bioactive natural products capable of controlling the formation of HCAs during cooking. For this purpose we have evaluated the effect of Rosa rugosa tea extract (RTE) on the formation of HCAs in ground beef patties fried at 160 degrees C or 220 degrees C. RTE is rich in phenolic compounds and capable of inhibiting the formation of free radicals. The pyrido[3,4-b]indole (norharman) and 1-methyl-9H-pyrido[3,4-b]indole (harman) contents were significantly (p < 0.05) decreased in RTE-treated patties at 220 degrees C. 9H-3 Amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2) and 3-amino-1,4-dimethyl 5H-pyrido-[4,3-b]indole acetate (Trp-P-1) were not detected at 160 degrees C and were statistically (p < 0.01) reduced at 220 degrees C compared to the control. RTE remarkably inhibited the formation of 2-amino-1-methyl-6-phenylimidazo[4,5 b]pyridine (PhIP) at 220 degrees C (p < 0.001) and at 160 degrees C (p < 0.05). 2-Amino-9H-pyrido[2,3-b]indole (AalphaC) and 2-amino-3-methyl-9H-pyrido[2,3-b] indole (MeAalphaC) were only detected in the control group at 160 degrees C but were comparatively (p > 0.05) similar in the control and treated groups at 220 degrees C. 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4 dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline (MeIQx), and 2-amino-3,4,8-trimethylimidazo[4,5-f]-quinoxaline (4,8 DiMeIQx) were not detected in any sample. Total HCAs were positively correlated with cooking loss. In the RTE-treated groups, 75% of the total HCAs were decreased at 160 degrees C and 46% at 220 degrees C, suggesting that RTE is effective at both temperatures and can be used during cooking at high temperatures to lessen the amount of HCAs formed. PMID- 26840289 TI - Metabolites of Siamenoside I and Their Distributions in Rats. AB - Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic pathways, a high-performance liquid chromatography electrospray ionization-ion trap-time of flight-multistage mass spectrometry (HPLC-ESI-IT-TOF-MS(n)) method was used to profile and identify its metabolites in rats. Altogether, 86 new metabolites were identified or tentatively identified, and 23 of them were also new metabolites of mogrosides. In rats, siamenoside I was found to undergo deglycosylation, hydroxylation, dehydrogenation, deoxygenation, isomerization, and glycosylation reactions. Among them, deoxygenation, pentahydroxylation, and didehydrogenation were novel metabolic reactions of mogrosides. The distributions of siamenoside I and its 86 metabolites in rat organs were firstly reported, and they were mainly distributed to intestine, stomach, kidney, and brain. The most widely distributed metabolite was mogroside IIIE. In addition, eight metabolites were bioactive according to literature. These findings would help to understand the metabolism and effective forms of siamenoside I and other mogrosides in vivo. PMID- 26840290 TI - Moving from Classical Ru-NHC to Neutral or Charged Rh-NHC Based Catalysts in Olefin Metathesis. AB - Considering the versatility of oxidation states of rhodium together with the successful background of ruthenium-N-heterocyclic carbene based catalysts in olefin metathesis, it is envisaged the exchange of the ruthenium of the latter catalysts by rhodium, bearing an open-shell neutral rhodium center, or a +1 charged one. In the framework of in silico experiments, density functional theory (DFT) calculations have been used to plot the first catalytic cycle that as a first step includes the release of the phosphine. DFT is, in this case, the tool that allows the discovery of the less endergonic reaction profile from the precatalytic species for the neutral catalyst with respect to the corresponding ruthenium one; increasing the endergonic character when dealing with the charged system. PMID- 26840291 TI - Self Organizing Map-Based Classification of Cathepsin k and S Inhibitors with Different Selectivity Profiles Using Different Structural Molecular Fingerprints: Design and Application for Discovery of Novel Hits. AB - The main step in a successful drug discovery pipeline is the identification of small potent compounds that selectively bind to the target of interest with high affinity. However, there is still a shortage of efficient and accurate computational methods with powerful capability to study and hence predict compound selectivity properties. In this work, we propose an affordable machine learning method to perform compound selectivity classification and prediction. For this purpose, we have collected compounds with reported activity and built a selectivity database formed of 153 cathepsin K and S inhibitors that are considered of medicinal interest. This database has three compound sets, two K/S and S/K selective ones and one non-selective KS one. We have subjected this database to the selectivity classification tool 'Emergent Self-Organizing Maps' for exploring its capability to differentiate selective cathepsin inhibitors for one target over the other. The method exhibited good clustering performance for selective ligands with high accuracy (up to 100 %). Among the possibilites, BAPs and MACCS molecular structural fingerprints were used for such a classification. The results exhibited the ability of the method for structure-selectivity relationship interpretation and selectivity markers were identified for the design of further novel inhibitors with high activity and target selectivity. PMID- 26840292 TI - Chemopreventive and Therapeutic Effects of Edible Berries: A Focus on Colon Cancer Prevention and Treatment. AB - Colon cancer is one of the most prevalent diseases across the world. Numerous epidemiological studies indicate that diets rich in fruit, such as berries, provide significant health benefits against several types of cancer, including colon cancer. The anticancer activities of berries are attributed to their high content of phytochemicals and to their relevant antioxidant properties. In vitro and in vivo studies have demonstrated that berries and their bioactive components exert therapeutic and preventive effects against colon cancer by the suppression of inflammation, oxidative stress, proliferation and angiogenesis, through the modulation of multiple signaling pathways such as NF-kappaB, Wnt/beta-catenin, PI3K/AKT/PKB/mTOR, and ERK/MAPK. Based on the exciting outcomes of preclinical studies, a few berries have advanced to the clinical phase. A limited number of human studies have shown that consumption of berries can prevent colorectal cancer, especially in patients at high risk (familial adenopolyposis or aberrant crypt foci, and inflammatory bowel diseases). In this review, we aim to highlight the findings of berries and their bioactive compounds in colon cancer from in vitro and in vivo studies, both on animals and humans. Thus, this review could be a useful step towards the next phase of berry research in colon cancer. PMID- 26840293 TI - Unusual Nitrogenous Phenalenone Derivatives from the Marine-Derived Fungus Coniothyrium cereale. AB - The new phenalenone metabolites 1, 2, 4, and 6 were isolated from the marine derived endophytic fungus Coniothyrium cereale, in addition to the ergostane-type sterol (3) and entatrovenetinone (5). Compounds 1 and 2 represent two unusual nitrogen-containing compounds, which are composed of a sterol portion condensed via two bonds to phenalenone derivatives. Compound 6, which contains unprecedented imine functionality between two carbonyl groups to form a oxepane imine-dione ring, exhibited a moderate cytotoxicity against K562, U266, and SKM1 cancer cell lines. Moreover, molecular docking studies were done on estrogen receptor alpha-ligand binding domain (ERalpha-LBD) to compounds 1 and 2 to correlate with binding energies and affinities calculated from molecular docking to the anti-proliferative activity. PMID- 26840294 TI - Thiourea-Modified TiO2 Nanorods with Enhanced Photocatalytic Activity. AB - Semiconductor TiO2 photocatalysis has attracted much attention due to its potential application in solving the problems of environmental pollution. In this paper, thiourea (CH4N2S) modified anatase TiO2 nanorods were fabricated by calcination of the mixture of TiO2 nanorods and thiourea at 600 degrees C for 2 h. It was found that only N element was doped into the lattice of TiO2 nanorods. With increasing the weight ratio of thiourea to TiO2 (R) from 0 to 8, the light harvesting ability of the photocatalyst steady increases. Both the crystallization and photocatalytic activity of TiO2 nanorods increase first and then decrease with increase in R value, and R2 sample showed the highest crystallization and photocatalytic activity in degradation of Brilliant Red X3B (X3B) and Rhodamine B (RhB) dyes under visible light irradiation (lambda > 420 nm). The increased visible-light photocatalytic activity of the prepared N-doped TiO2 nanorods is due to the synergistic effects of the enhanced crystallization, improved light-harvesting ability and reduced recombination rate of photo generated electron-hole pairs. Note that the enhanced visible photocatalytic activity of N-doped nanorods is not based on the scarification of their UV photocatalytic activity. PMID- 26840295 TI - Ginsenoside-Rd Promotes Neurite Outgrowth of PC12 Cells through MAPK/ERK- and PI3K/AKT-Dependent Pathways. AB - Panax ginseng is a famous herbal medicine widely used in Asia. Ginsenosides have been identified as the principle active ingredients for Panax ginseng's biological activity, among which ginsenoside Rd (Rd) attracts extensive attention for its obvious neuroprotective activities. Here we investigated the effect of Rd on neurite outgrowth, a crucial process associated with neuronal repair. PC12 cells, which respond to nerve growth factor (NGF) and serve as a model for neuronal cells, were treated with different concentrations of Rd, and then their neurite outgrowth was evaluated. Our results showed that 10 MUM Rd significantly increased the percentages of long neurite- and branching neurite-bearing cells, compared with respective controls. The length of the longest neurites and the total length of neurites in Rd-treated PC12 cells were much longer than that of respective controls. We also showed that Rd activated ERK1/2 and AKT but not PKC signalings, and inhibition of ERK1/2 by PD98059 or/and AKT by LY294002 effectively attenuated Rd-induced neurite outgrowth. Moreover, Rd upregulated the expression of GAP-43, a neuron-specific protein involved in neurite outgrowth, while PD98059 or/and LY294002 decreased Rd-induced increased GAP-43 expression. Taken together, our results provided the first evidence that Rd may promote the neurite outgrowth of PC12 cells by upregulating GAP-43 expression via ERK- and ARK-dependent signaling pathways. PMID- 26840296 TI - Clinical Genetic Aspects of ASD Spectrum Disorders. AB - Early presumptions opined that autism spectrum disorder (ASD) was related to the rearing of these children by emotionally-distant mothers. Advances in the 1960s and 1970s clearly demonstrated the biologic basis of autism with a high heritability. Recent advances have demonstrated that specific etiologic factors in autism spectrum disorders can be identified in 30%-40% of cases. Based on early reports newer, emerging genomic technologies are likely to increase this diagnostic yield to over 50%. To date these investigations have focused on etiologic factors that are largely mono-factorial. The currently undiagnosed causes of ASDs will likely be found to have causes that are more complex. Epigenetic, multiple interacting loci, and four dimensional causes (with timing as a variable) are likely to be associated with the currently unidentifiable cases. Today, the "Why" is more important than ever. Understanding the causes of ASDs help inform families of important issues such as recurrence risk, prognosis, natural history, and predicting associated co-morbid medical conditions. In the current era of emerging efforts in "personalized medicine", identifying an etiology will be critical in identifying endo-phenotypic groups and individual variations that will allow for tailored treatment for persons with ASD. PMID- 26840297 TI - Melatonin Suppresses the Growth of Ovarian Cancer Cell Lines (OVCAR-429 and PA-1) and Potentiates the Effect of G1 Arrest by Targeting CDKs. AB - Melatonin is found in animals as well as plants. In animals, it is a hormone that anticipates the daily onset of darkness and regulates physiological functions, such as sleep timing, blood pressure, and reproduction. Melatonin has also been found to have anti-tumor properties. Malignant cancers are the most common cause of death, and the mortality rate of ovarian tumor is the highest among gynecological diseases. This study investigated the anti-tumor effects of melatonin on the ovarian cancer lines, OVCAR-429 and PA-1. We observed the accumulation of melatonin-treated cells in the G1 phase due to the down regulation of CDK 2 and 4. Our results suggest that in addition to the known effects on prevention, melatonin may also provide anti-tumor activity in established ovarian cancer. PMID- 26840298 TI - Induction of Apoptosis by PQ1, a Gap Junction Enhancer that Upregulates Connexin 43 and Activates the MAPK Signaling Pathway in Mammary Carcinoma Cells. AB - The mechanism of gap junction enhancer (PQ1) induced cytotoxicity is thought to be attributed to the change in connexin 43 (Cx43) expression; therefore, the effects of Cx43 modulation in cell survival were investigated in mammary carcinoma cells (FMC2u) derived from a malignant neoplasm of a female FVB/N Tg(MMTV-PyVT)634Mul/J (PyVT) transgenic mouse. PQ1 was determined to have an IC50 of 6.5 uM in FMC2u cells, while inducing an upregulation in Cx43 expression. The effects of Cx43 modulation in FMC2u cell survival was determined through transfection experiments with Cx43 cDNA, which induced an elevated level of protein expression similar to that seen with PQ1 exposure, or siRNA to silence Cx43 protein expression. Overexpression or silencing of Cx43 led to a reduction or an increase in cell viability, respectively. The mitogen-activated protein kinase (MAPK) family has been implicated in the regulation of cell survival and cell death; therefore, the gap junctional intercellular communication (GJIC) independent function of PQ1 and Cx43 in the Raf/Mitogen-activated protein kinase/ERK kinase/extracellular-signal-regulated kinase (Raf-MEK-ERK) cascade of cellular survival and p38 MAPK-dependent pathway of apoptosis were explored. PQ1 treatment activated p44/42 MAPK, while the overexpression of Cx43 resulted in a reduced expression. This suggests that PQ1 affects the Raf-MEK-ERK cascade independent of Cx43 upregulation. Both overexpression of Cx43 and PQ1 treatment stimulated an increase in the phosphorylated form of p38-MAPK, reduced levels of the anti-apoptotic protein Bcl-2, and increased the cleavage of pro-caspase-3. Silencing of Cx43 protein expression led to a reduction in the phosphorylation of p38-MAPK and an increase in Bcl-2 expression. The mechanism behind PQ1-induced cytotoxicity in FMC2u mammary carcinoma cells is thought to be attributed to the change in Cx43 expression. Furthermore, PQ1-induced apoptosis through the upregulation of Cx43 may depend on p38 MAPK, highlighting that the effect of PQ1 on gap junctions as well as cellular survival via a MAPK-dependent pathway. PMID- 26840299 TI - Plasma Monocyte Chemoattractant Protein-1 Level as a Predictor of the Severity of Community-Acquired Pneumonia. AB - Monocyte chemoattractant protein (MCP)-1 increases in the serum of immunocompetent patients with community-acquired pneumonia (CAP). However, the correlation between the circulating level of MCP-1 and severity of CAP remains unclear. This study investigated differential changes in the plasma MCP-1 levels of patients with CAP before and after an antibiotic treatment and further analyzes the association between the CAP severity and MCP-1 levels. We measured the plasma MCP-1 levels of 137 patients with CAP and 74 healthy controls by using a commercial enzyme-linked immunosorbent assay. Upon initial hospitalization, Acute Physiology and Chronic Health Evaluation II (APACHE II); confusion, urea level, respiratory rate, blood pressure, and age of >64 years (CURB-65); and pneumonia severity index (PSI) scores were determined for assessing the CAP severity in these patients. The antibiotic treatment reduced the number of white blood cells (WBCs) and neutrophils as well as the level of C-reactive protein (CRP) and MCP-1. The plasma MCP-1 level, but not the CRP level or WBC count, correlated with the CAP severity according to the PSI (r = 0.509, p < 0.001), CURB-65 (r = 0.468, p < 0.001), and APACHE II (r = 0.360, p < 0.001) scores. We concluded that MCP-1 levels act in the development of CAP and are involved in the severity of CAP. PMID- 26840300 TI - miR-30-5p Regulates Muscle Differentiation and Alternative Splicing of Muscle Related Genes by Targeting MBNL. AB - MicroRNAs (miRNAs), a class of single stranded, small (~22 nucleotides), non coding RNAs, play an important role in muscle development. We focused on the role of the miR-30-5p family during bovine muscle development from previous high throughput sequencing results and analyzed their expression profiles. MHC and MyoG mRNAs expression as well as their proteins were suppressed in differentiated C2C12 cells, suggesting the importance of miR-30-5p in muscle development. MBNL, the candidate target of miR-30-5p, is an alternative splicing regulation factor. MBNL1 and MBNL3 have opposite effects on muscle differentiation. Our results confirmed that miR-30a-5p and miR-30e-5p repress the expression of MBNL1, MBNL2 and MBNL3, whereas miR-30b-5p inhibits MBNL1 and MBNL2 expression. This provides direct evidence that MBNL expression can be flexibly regulated by miR-30-5p. Previous studies showed that MBNL1 promotes exon inclusion of two muscle-related genes (Trim55 and INSR). Through RNA splicing studies, we found that miR-30-5p had an effect on their alternative splicing, which means miR-30-5p via MBNL1 could be integrated into muscle signaling pathways in which INSR or Trim55 are located. In conclusion, miR-30-5p could inhibit muscle cell differentiation and regulate the alternative splicing of Trim55 and INSR by targeting MBNL. These results promote the understanding of the function of miRNAs in muscle development. PMID- 26840301 TI - Immune Dysfunction Associated with Abnormal Bone Marrow-Derived Mesenchymal Stroma Cells in Senescence Accelerated Mice. AB - Senescence accelerated mice (SAM) are a group of mice that show aging-related diseases, and SAM prone 10 (SAMP10) show spontaneous brain atrophy and defects in learning and memory. Our previous report showed that the thymus and the percentage of T lymphocytes are abnormal in the SAMP10, but it was unclear whether the bone marrow-derived mesenchymal stroma cells (BMMSCs) were abnormal, and whether they played an important role in regenerative medicine. We thus compared BMMSCs from SAMP10 and their control, SAM-resistant (SAMR1), in terms of cell cycle, oxidative stress, and the expression of PI3K and mitogen-activated protein kinase (MAPK). Our cell cycle analysis showed that cell cycle arrest occurred in the G0/G1 phase in the SAMP10. We also found increased reactive oxygen stress and decreased PI3K and MAPK on the BMMSCs. These results suggested the BMMSCs were abnormal in SAMP10, and that this might be related to the immune system dysfunction in these mice. PMID- 26840302 TI - Identification of Powdery Mildew Responsive Genes in Hevea brasiliensis through mRNA Differential Display. AB - Powdery mildew is an important disease of rubber trees caused by Oidium heveae B. A. Steinmann. As far as we know, none of the resistance genes related to powdery mildew have been isolated from the rubber tree. There is little information available at the molecular level regarding how a rubber tree develops defense mechanisms against this pathogen. We have studied rubber tree mRNA transcripts from the resistant RRIC52 cultivar by differential display analysis. Leaves inoculated with the spores of O. heveae were collected from 0 to 120 hpi in order to identify pathogen-regulated genes at different infection stages. We identified 78 rubber tree genes that were differentially expressed during the plant-pathogen interaction. BLAST analysis for these 78 ESTs classified them into seven functional groups: cell wall and membrane pathways, transcription factor and regulatory proteins, transporters, signal transduction, phytoalexin biosynthesis, other metabolism functions, and unknown functions. The gene expression for eight of these genes was validated by qRT-PCR in both RRIC52 and the partially susceptible Reyan 7-33-97 cultivars, revealing the similar or differential changes of gene expressions between these two cultivars. This study has improved our overall understanding of the molecular mechanisms of rubber tree resistance to powdery mildew. PMID- 26840303 TI - Enhancement of Alkaline Protease Activity and Stability via Covalent Immobilization onto Hollow Core-Mesoporous Shell Silica Nanospheres. AB - The stability and reusability of soluble enzymes are of major concerns, which limit their industrial applications. Herein, alkaline protease from Bacillus sp. NPST-AK15 was immobilized onto hollow core-mesoporous shell silica (HCMSS) nanospheres. Subsequently, the properties of immobilized proteases were evaluated. Non-, ethane- and amino-functionalized HCMSS nanospheres were synthesized and characterized. NPST-AK15 was immobilized onto the synthesized nano-supports by physical and covalent immobilization approaches. However, protease immobilization by covalent attachment onto the activated HCMSS-NH2 nanospheres showed highest immobilization yield (75.6%) and loading capacity (88.1 MUg protein/mg carrier) and was applied in the further studies. In comparison to free enzyme, the covalently immobilized protease exhibited a slight shift in the optimal pH from 10.5 to 11.0, respectively. The optimum temperature for catalytic activity of both free and immobilized enzyme was seen at 60 degrees C. However, while the free enzyme was completely inactivated when treated at 60 degrees C for 1 h the immobilized enzyme still retained 63.6% of its initial activity. The immobilized protease showed higher V(max), k(cat) and k(cat)/K(m), than soluble enzyme by 1.6-, 1.6- and 2.4-fold, respectively. In addition, the immobilized protease affinity to the substrate increased by about 1.5-fold. Furthermore, the enzyme stability in various organic solvents was significantly enhanced upon immobilization. Interestingly, the immobilized enzyme exhibited much higher stability in several commercial detergents including OMO, Tide, Ariel, Bonux and Xra by up to 5.2-fold. Finally, the immobilized protease maintained significant catalytic efficiency for twelve consecutive reaction cycles. These results suggest the effectiveness of the developed nanobiocatalyst as a candidate for detergent formulation and peptide synthesis in non-aqueous media. PMID- 26840304 TI - Liensinine- and Neferine-Induced Cardiotoxicity in Primary Neonatal Rat Cardiomyocytes and Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes. AB - Due to drug-induced potential congestive heart failure and irreversible dilated cardiomyopathies, preclinical evaluation of cardiac dysfunction is important to assess the safety of traditional or novel treatments. The embryos of Nelumbo nucifera Gaertner seeds are a homology of traditional Chinese medicine and food. In this study, we applied the real time cellular analysis (RTCA) Cardio system, which can real-time monitor the contractility of cardiomyocytes (CMs), to evaluate drug safety in rat neonatal CMs and human induced pluripotent stem cell derived cardiomyocytes (hiPS-CMs). This study showed detailed biomechanical CM contractility in vitro, and provided insights into the cardiac dysfunctions associated with liensinine and neferine treatment. These effects exhibited dose and time-dependent recovery. Neferine showed stronger blocking effect in rat neonatal CMs than liensinine. In addition, the effects of liensinine and neferine were further evaluated on hiPS-CMs. Our study also indicated that both liensinine and neferine can cause disruption of calcium homeostasis. For the first time, we demonstrated the potential cardiac side effects of liensinine or neferine. While the same inhibition was observed on hiPS-CMs, more importantly, this study introduced an efficient and effective approach to evaluate the cardiotoxicity of the existing and novel drug candidates. PMID- 26840305 TI - Applications and Challenges for Use of Cell-Penetrating Peptides as Delivery Vectors for Peptide and Protein Cargos. AB - The hydrophilic nature of peptides and proteins renders them impermeable to cell membranes. Thus, in order to successfully deliver peptide and protein-based therapeutics across the plasma membrane or epithelial and endothelial barriers, a permeation enhancing strategy must be employed. Cell-penetrating peptides (CPPs) constitute a promising tool and have shown applications for peptide and protein delivery into cells as well as across various epithelia and the blood-brain barrier (BBB). CPP-mediated delivery of peptides and proteins may be pursued via covalent conjugation of the CPP to the cargo peptide or protein or via physical complexation obtained by simple bulk-mixing of the CPP with its cargo. Both approaches have their pros and cons, and which is the better choice likely relates to the physicochemical properties of the CPP and its cargo as well as the route of administration, the specific barrier and the target cell. Besides the physical barrier, a metabolic barrier must be taken into consideration when applying peptide-based delivery vectors, such as the CPPs, and stability enhancing strategies are commonly employed to prolong the CPP half-life. The mechanisms by which CPPs translocate cell membranes are believed to involve both endocytosis and direct translocation, but are still widely investigated and discussed. The fact that multiple factors influence the mechanisms responsible for cellular CPP internalization and the lack of sensitive methods for detection of the CPP, and in some cases the cargo, further complicates the design and conduction of conclusive mechanistic studies. PMID- 26840306 TI - Atrogin-1 Deficiency Leads to Myopathy and Heart Failure in Zebrafish. AB - Orchestrated protein synthesis and degradation is fundamental for proper cell function. In muscle, impairment of proteostasis often leads to severe cellular defects finally interfering with contractile function. Here, we analyze for the first time the role of Atrogin-1, a muscle-specific E3 ubiquitin ligase known to be involved in the regulation of protein degradation via the ubiquitin proteasome and the autophagy/lysosome systems, in the in vivo model system zebrafish (Danio rerio). We found that targeted inactivation of zebrafish Atrogin-1 leads to progressive impairment of heart and skeletal muscle function and disruption of muscle structure without affecting early cardiogenesis and skeletal muscle development. Autophagy is severely impaired in Atrogin-1-deficient zebrafish embryos resulting in the disturbance of the cytoarchitecture of cardiomyocytes and skeletal muscle cells. These observations are consistent with molecular and ultrastructural findings in an Atrogin-1 knockout mouse and demonstrate that the zebrafish is a suitable vertebrate model to study the molecular mechanisms of Atrogin-1-mediated autophagic muscle pathologies and to screen for novel therapeutically active substances in high-throughput in vivo small compound screens (SCS). PMID- 26840307 TI - Biological Evaluation of Double Point Modified Analogues of 1,25-Dihydroxyvitamin D2 as Potential Anti-Leukemic Agents. AB - Structurally similar double-point modified analogues of 1,25-dihydroxyvitamin D2 (1,25D2) were screened in vitro for their pro-differentiating activity against the promyeloid cell line HL60. Their affinities towards human full length vitamin D receptor (VDR) and metabolic stability against human vitamin D 24-hydroxylase (CYP24A1) were also tested. The analogues (PRI-1730, PRI-1731, PRI-1732, PRI-1733 and PRI-1734) contained 5,6-trans modification of the A-ring and of the triene system, additional hydroxyl or unsaturation at C-22 in the side chain and reversed absolute configuration (24-epi) at C-24 of 1,25D2. As presented in this paper, introduction of selected structural modifications simultaneously in two distinct parts of the vitamin D molecule resulted in a divergent group of analogues. Analogues showed lower VDR affinity in comparison to that of the parent hormones, 1,25D2 and 1,25D3, and they caused effective HL60 cell differentiation only at high concentrations of 100 nM and above. Unexpectedly, introducing of a 5,6-trans modification combined with C-22 hydroxyl and 24-epi configuration switched off entirely the cell differentiation activity of the analogue (PRI-1734). However, this analogue remained a moderate substrate for CYP24A1, as it was metabolized at 22%, compared to 35% for 1,25D2. Other analogues from this series were either less (12% for PRI-1731 and PRI-1733) or more (52% for PRI-1732) resistant to the enzymatic deactivation. Although the inactive analogue PRI-1734 failed to show VDR antagonism, when tested in HL60 cells, its structure might be a good starting point for our design of a vitamin D antagonist. PMID- 26840308 TI - Prioritization of Susceptibility Genes for Ectopic Pregnancy by Gene Network Analysis. AB - Ectopic pregnancy is a very dangerous complication of pregnancy, affecting 1%-2% of all reported pregnancies. Due to ethical constraints on human biopsies and the lack of suitable animal models, there has been little success in identifying functionally important genes in the pathogenesis of ectopic pregnancy. In the present study, we developed a random walk-based computational method named TM rank to prioritize ectopic pregnancy-related genes based on text mining data and gene network information. Using a defined threshold value, we identified five top ranked genes: VEGFA (vascular endothelial growth factor A), IL8 (interleukin 8), IL6 (interleukin 6), ESR1 (estrogen receptor 1) and EGFR (epidermal growth factor receptor). These genes are promising candidate genes that can serve as useful diagnostic biomarkers and therapeutic targets. Our approach represents a novel strategy for prioritizing disease susceptibility genes. PMID- 26840309 TI - The Role of Endoplasmic Reticulum Stress and Unfolded Protein Response in Atherosclerosis. AB - Pathogenesis of atherosclerosis is a complex process involving several metabolic and signalling pathways. Accumulating evidence demonstrates that endoplasmic reticulum stress and associated apoptosis can be induced in the pathological conditions of atherosclerotic lesions and contribute to the disease progression. Notably, they may play a role in the development of vulnerable plaques that induce thrombosis and are therefore especially dangerous. Endoplasmic reticulum stress response is regulated by several signaling mechanisms that involve protein kinases and transcription factors. Some of these molecules can be regarded as potential therapeutic targets to improve treatment of atherosclerosis. In this review we will discuss the role of endoplasmic reticulum stress and apoptosis in atherosclerosis development in different cell types and summarize the current knowledge on potential therapeutic agents targeting molecules regulating these pathways and their possible use for anti-atherosclerotic therapy. PMID- 26840312 TI - Mobility-Enhanced Reliable Geographical Forwarding in Cognitive Radio Sensor Networks. AB - The emergence of the Internet of Things and the proliferation of mobile wireless devices has brought the area of mobile cognitive radio sensor networks (MCRSN) to the research spot light. Notwithstanding the potentials of CRSNs in terms of opportunistic channel usage for bursty traffic, the effect of the mobility of resource-constrained nodes to route stability, mobility-induced spatio-temporal spectral opportunities and primary user (PU) protection still remain open issues that need to be jointly addressed. To this effect, this paper proposes a mobile reliable geographical forwarding routing (MROR) protocol. MROR provides a robust mobile framework for geographical forwarding that is based on a mobility-induced channel availability model. It presents a comprehensive routing strategy that considers PU activity (to take care of routes that have to be built through PU coverage), PU signal protection (by the introduction of a mobility-induced guard (mguard) distance) and the random mobility-induced spatio-temporal spectrum opportunities (for enhancement of throughput). It also addresses the issue of frequent route maintenance that arises when speeds of the mobile nodes are considered as a routing metric. As a result, simulation has shown the ability of MROR to reduce the route failure rate by about 65% as against other schemes. In addition, further results show that MROR can improve both the throughput and goodput at the sink in an energy-efficient manner that is required in CRSNs as against compared works. PMID- 26840311 TI - Key Management Scheme Based on Route Planning of Mobile Sink in Wireless Sensor Networks. AB - In many wireless sensor network application scenarios the key management scheme with a Mobile Sink (MS) should be fully investigated. This paper proposes a key management scheme based on dynamic clustering and optimal-routing choice of MS. The concept of Traveling Salesman Problem with Neighbor areas (TSPN) in dynamic clustering for data exchange is proposed, and the selection probability is used in MS route planning. The proposed scheme extends static key management to dynamic key management by considering the dynamic clustering and mobility of MSs, which can effectively balance the total energy consumption during the activities. Considering the different resources available to the member nodes and sink node, the session key between cluster head and MS is established by modified an ECC encryption with Diffie-Hellman key exchange (ECDH) algorithm and the session key between member node and cluster head is built with a binary symmetric polynomial. By analyzing the security of data storage, data transfer and the mechanism of dynamic key management, the proposed scheme has more advantages to help improve the resilience of the key management system of the network on the premise of satisfying higher connectivity and storage efficiency. PMID- 26840313 TI - Robust Tomato Recognition for Robotic Harvesting Using Feature Images Fusion. AB - Automatic recognition of mature fruits in a complex agricultural environment is still a challenge for an autonomous harvesting robot due to various disturbances existing in the background of the image. The bottleneck to robust fruit recognition is reducing influence from two main disturbances: illumination and overlapping. In order to recognize the tomato in the tree canopy using a low-cost camera, a robust tomato recognition algorithm based on multiple feature images and image fusion was studied in this paper. Firstly, two novel feature images, the a*-component image and the I-component image, were extracted from the L*a*b* color space and luminance, in-phase, quadrature-phase (YIQ) color space, respectively. Secondly, wavelet transformation was adopted to fuse the two feature images at the pixel level, which combined the feature information of the two source images. Thirdly, in order to segment the target tomato from the background, an adaptive threshold algorithm was used to get the optimal threshold. The final segmentation result was processed by morphology operation to reduce a small amount of noise. In the detection tests, 93% target tomatoes were recognized out of 200 overall samples. It indicates that the proposed tomato recognition method is available for robotic tomato harvesting in the uncontrolled environment with low cost. PMID- 26840314 TI - System Error Compensation Methodology Based on a Neural Network for a Micromachined Inertial Measurement Unit. AB - Errors compensation of micromachined-inertial-measurement-units (MIMU) is essential in practical applications. This paper presents a new compensation method using a neural-network-based identification for MIMU, which capably solves the universal problems of cross-coupling, misalignment, eccentricity, and other deterministic errors existing in a three-dimensional integrated system. Using a neural network to model a complex multivariate and nonlinear coupling system, the errors could be readily compensated through a comprehensive calibration. In this paper, we also present a thermal-gas MIMU based on thermal expansion, which measures three-axis angular rates and three-axis accelerations using only three thermal-gas inertial sensors, each of which capably measures one-axis angular rate and one-axis acceleration simultaneously in one chip. The developed MIMU (100 * 100 * 100 mm3) possesses the advantages of simple structure, high shock resistance, and large measuring ranges (three-axes angular rates of +/-4000 degrees /s and three-axes accelerations of +/- 10 g) compared with conventional MIMU, due to using gas medium instead of mechanical proof mass as the key moving and sensing elements. However, the gas MIMU suffers from cross-coupling effects, which corrupt the system accuracy. The proposed compensation method is, therefore, applied to compensate the system errors of the MIMU. Experiments validate the effectiveness of the compensation, and the measurement errors of three-axis angular rates and three-axis accelerations are reduced to less than 1% and 3% of uncompensated errors in the rotation range of +/-600 degrees /s and the acceleration range of +/- 1 g, respectively. PMID- 26840310 TI - Pharmacological Modulators of Endoplasmic Reticulum Stress in Metabolic Diseases. AB - The endoplasmic reticulum (ER) is the principal organelle responsible for correct protein folding, a step in protein synthesis that is critical for the functional conformation of proteins. ER stress is a primary feature of secretory cells and is involved in the pathogenesis of numerous human diseases, such as certain neurodegenerative and cardiometabolic disorders. The unfolded protein response (UPR) is a defense mechanism to attenuate ER stress and maintain the homeostasis of the organism. Two major degradation systems, including the proteasome and autophagy, are involved in this defense system. If ER stress overwhelms the capacity of the cell's defense mechanisms, apoptotic death may result. This review is focused on the various pharmacological modulators that can protect cells from damage induced by ER stress. The possible mechanisms for cytoprotection are also discussed. PMID- 26840315 TI - Load Measurement on Foundations of Rockfall Protection Systems. AB - Rockfall protection barriers are connected to the ground using steel cables fixed with anchors and foundations for the steel posts. It is common practice to measure the forces in the cables, while to date measurements of forces in the foundations have been inadequately resolved. An overview is presented of existing methods to measure the loads on the post foundations of rockfall protection barriers. Addressing some of the inadequacies of existing approaches, a novel sensor unit is presented that is able to capture the forces acting on post foundations in all six degrees of freedom. The sensor unit consists of four triaxial force sensors placed between two steel plates. To correctly convert the measurements into the directional forces acting on the foundation a special in situ calibration procedure is proposed that delivers a corresponding conversion matrix. PMID- 26840316 TI - All-Digital Time-Domain CMOS Smart Temperature Sensor with On-Chip Linearity Enhancement. AB - This paper proposes the first all-digital on-chip linearity enhancement technique for improving the accuracy of the time-domain complementary metal-oxide semiconductor (CMOS) smart temperature sensor. To facilitate on-chip application and intellectual property reuse, an all-digital time-domain smart temperature sensor was implemented using 90 nm Field Programmable Gate Arrays (FPGAs). Although the inverter-based temperature sensor has a smaller circuit area and lower complexity, two-point calibration must be used to achieve an acceptable inaccuracy. With the help of a calibration circuit, the influence of process variations was reduced greatly for one-point calibration support, reducing the test costs and time. However, the sensor response still exhibited a large curvature, which substantially affected the accuracy of the sensor. Thus, an on chip linearity-enhanced circuit is proposed to linearize the curve and achieve a new linearity-enhanced output. The sensor was implemented on eight different Xilinx FPGA using 118 slices per sensor in each FPGA to demonstrate the benefits of the linearization. Compared with the unlinearized version, the maximal inaccuracy of the linearized version decreased from 5 degrees C to 2.5 degrees C after one-point calibration in a range of -20 degrees C to 100 degrees C. The sensor consumed 95 MUW using 1 kSa/s. The proposed linearity enhancement technique significantly improves temperature sensing accuracy, avoiding costly curvature compensation while it is fully synthesizable for future Very Large Scale Integration (VLSI) system. PMID- 26840317 TI - Current Sensor Fault Reconstruction for PMSM Drives. AB - This paper deals with a current sensor fault reconstruction algorithm for the torque closed-loop drive system of an interior PMSM. First, sensor faults are equated to actuator ones by a new introduced state variable. Then, in alphabeta coordinates, based on the motor model with active flux linkage, a current observer is constructed with a specific sliding mode equivalent control methodology to eliminate the effects of unknown disturbances, and the phase current sensor faults are reconstructed by means of an adaptive method. Finally, an alphabeta axis current fault processing module is designed based on the reconstructed value. The feasibility and effectiveness of the proposed method are verified by simulation and experimental tests on the RT-LAB platform. PMID- 26840318 TI - A Novel Gas Sensor Based on MgSb2O6 Nanorods to Indicate Variations in Carbon Monoxide and Propane Concentrations. AB - Bystromite (MgSb2O6) nanorods were prepared using a colloidal method in the presence of ethylenediamine, after a calcination step at 800 degrees C in static air. From X-ray powder diffraction analyses, a trirutile-type structure with lattice parameters a = 4.64 A and c = 9.25 A and space group P42/mnm was identified. Using scanning electron microscopy (SEM), microrods with sizes from 0.2 to 1.6 MUm were observed. Transmission electron microscopy (TEM) analyses revealed that the nanorods had a length of ~86 nm and a diameter ~23.8 nm. The gas-sensing properties of these nanostructures were tested using pellets elaborated with powders of the MgSb2O6 oxide (calcined at 800 degrees C) at temperatures 23, 150, 200, 250 and 300 degrees C. The pellets were exposed to different concentrations of carbon monoxide (CO) and propane (C3H8) at these temperatures. The results showed that the MgSb2O6 nanorods possess excellent stability and high sensitivity in these atmospheres. PMID- 26840319 TI - Secure and Privacy-Preserving Body Sensor Data Collection and Query Scheme. AB - With the development of body sensor networks and the pervasiveness of smart phones, different types of personal data can be collected in real time by body sensors, and the potential value of massive personal data has attracted considerable interest recently. However, the privacy issues of sensitive personal data are still challenging today. Aiming at these challenges, in this paper, we focus on the threats from telemetry interface and present a secure and privacy preserving body sensor data collection and query scheme, named SPCQ, for outsourced computing. In the proposed SPCQ scheme, users' personal information is collected by body sensors in different types and converted into multi-dimension data, and each dimension is converted into the form of a number and uploaded to the cloud server, which provides a secure, efficient and accurate data query service, while the privacy of sensitive personal information and users' query data is guaranteed. Specifically, based on an improved homomorphic encryption technology over composite order group, we propose a special weighted Euclidean distance contrast algorithm (WEDC) for multi-dimension vectors over encrypted data. With the SPCQ scheme, the confidentiality of sensitive personal data, the privacy of data users' queries and accurate query service can be achieved in the cloud server. Detailed analysis shows that SPCQ can resist various security threats from telemetry interface. In addition, we also implement SPCQ on an embedded device, smart phone and laptop with a real medical database, and extensive simulation results demonstrate that our proposed SPCQ scheme is highly efficient in terms of computation and communication costs. PMID- 26840320 TI - A Personal, Distributed Exposimeter: Procedure for Design, Calibration, Validation, and Application. AB - This paper describes, for the first time, the procedure for the full design, calibration, uncertainty analysis, and practical application of a personal, distributed exposimeter (PDE) for the detection of personal exposure in the Global System for Mobile Communications (GSM) downlink (DL) band around 900 MHz (GSM 900 DL). The PDE is a sensor that consists of several body-worn antennas. The on-body location of these antennas is investigated using numerical simulations and calibration measurements in an anechoic chamber. The calibration measurements and the simulations result in a design (or on-body setup) of the PDE. This is used for validation measurements and indoor radio frequency (RF) exposure measurements in Ghent, Belgium. The main achievements of this paper are: first, the demonstration, using both measurements and simulations, that a PDE consisting of multiple on-body textile antennas will have a lower measurement uncertainty for personal RF exposure than existing on-body sensors; second, a validation of the PDE, which proves that the device correctly estimates the incident power densities; and third, a demonstration of the usability of the PDE for real exposure assessment measurements. To this aim, the validated PDE is used for indoor measurements in a residential building in Ghent, Belgium, which yield an average incident power density of 0.018 mW/m2. PMID- 26840321 TI - Accuracy and Resolution Analysis of a Direct Resistive Sensor Array to FPGA Interface. AB - Resistive sensor arrays are formed by a large number of individual sensors which are distributed in different ways. This paper proposes a direct connection between an FPGA and a resistive array distributed in M rows and N columns, without the need of analog-to-digital converters to obtain resistance values in the sensor and where the conditioning circuit is reduced to the use of a capacitor in each of the columns of the matrix. The circuit allows parallel measurements of the N resistors which form each of the rows of the array, eliminating the resistive crosstalk which is typical of these circuits. This is achieved by an addressing technique which does not require external elements to the FPGA. Although the typical resistive crosstalk between resistors which are measured simultaneously is eliminated, other elements that have an impact on the measurement of discharge times appear in the proposed architecture and, therefore, affect the uncertainty in resistance value measurements; these elements need to be studied. Finally, the performance of different calibration techniques is assessed experimentally on a discrete resistor array, obtaining for a new model of calibration, a maximum relative error of 0.066% in a range of resistor values which correspond to a tactile sensor. PMID- 26840322 TI - Daily Rhythms of Hunger and Satiety in Healthy Men during One Week of Sleep Restriction and Circadian Misalignment. AB - The impact of sleep restriction on the endogenous circadian rhythms of hunger and satiety were examined in 28 healthy young men. Participants were scheduled to 2 * 24-h days of baseline followed by 8 * 28-h days of forced desynchrony during which sleep was either moderately restricted (equivalent to 6 h in bed/24 h; n = 14) or severely restricted (equivalent to 4 h in bed/24 h; n = 14). Self-reported hunger and satisfaction were assessed every 2.5 h during wake periods using visual analogue scales. Participants were served standardised meals and snacks at regular intervals and were not permitted to eat ad libitum. Core body temperature was continuously recorded with rectal thermistors to determine circadian phase. Both hunger and satiety exhibited a marked endogenous circadian rhythm. Hunger was highest, and satiety was lowest, in the biological evening (i.e., ~17:00 21:00 h) whereas hunger was lowest, and satiety was highest in the biological night (i.e., 01:00-05:00 h). The results are consistent with expectations based on previous reports and may explain in some part the decrease in appetite that is commonly reported by individuals who are required to work at night. Interestingly, the endogenous rhythms of hunger and satiety do not appear to be altered by severe--as compared to moderate--sleep restriction. PMID- 26840323 TI - Fatigue in Emergency Services Operations: Assessment of the Optimal Objective and Subjective Measures Using a Simulated Wildfire Deployment. AB - Under controlled laboratory conditions, neurobehavioral assays such as the Psychomotor Vigilance Task (PVT) are sensitive to increasing levels of fatigue, and in general, tend to correlate with subjective ratings. However, laboratory studies specifically curtail physical activity, potentially limiting the applicability of such findings to field settings that involve physical work. In addition, laboratory studies typically involve healthy young male participants that are not always representative of a typical working population. In order to determine whether these findings extend to field-like conditions, we put 88 Australian volunteer firefighters through a multi-day firefighting simulation. Participants were required to perform real-world physical and cognitive tasks under conditions of elevated temperature and moderate sleep restriction. We aimed to examine changes in fatigue in an effort to determine the optimum objective and subjective measures. Objective and subjective tests were sensitive to fatigue outside laboratory conditions. The PVT was the most sensitive assay of objective fatigue, with the Samn-Perelli fatigue scale the most sensitive of the subjective measures. The Samn-Perilli fatigue scale correlated best with PVT performance, but explained a small amount of variance. Although the Samn-Perelli scale can be easily administered in the field, the wide range of individual variance limits its efficacy as a once-off assessment tool. Rather, fatigue measures should be applied as a component of a broader fatigue risk management system. Findings provide firefighting agencies, and other occupations involving physical work, guidance as to the most sensitive and specific measures for assessing fatigue in their personnel. PMID- 26840324 TI - Blood Pressure, Sleep Quality and Fatigue in Shift Working Police Officers: Effects of a Twelve Hour Roster System on Cardiovascular and Sleep Health. AB - BACKGROUND: Police officers have been reported to exhibit a high incidence of pathologies, which present prematurely in an otherwise healthy population. Shift work has also been associated with an increased risk of cardiovascular and sleep disorders, attributable to its propensity for circadian rhythm dysfunction. However, contention exists as to whether shift work has a direct effect upon blood pressure (BP) regulation. METHODS: This cross-sectional study sought to determine changes in BP and associations with the overall sleep quality and fatigue in 206 general duties police officers (n = 140 males) of the New South Wales Police Force in Australia. The subjects' BP was assessed before and after their twelve hour shift, during which time they also completed the Lifestyle Appraisal Questionnaire, Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale and Fatigue Severity Scale (FSS). RESULTS: Poor sleep quality (PSQI) and fatigue severity (FSS) were found to predominate in the sample (69% and 51% respectively). Although there was no change in BP for male participants, female officers' systolic blood pressure (SBP) was found to increase significantly across the shift (p < 0.001), but with no change found in females' diastolic blood pressure (DBP). Finally, higher pre and post-shift SBP (r = 0.26, p = 0.001; r = -0.25, p = 0.001, respectively) and DBP (r = -0.26, p = 0.001; r = -0.26, p = 0.001, respectively) were significantly correlated with lower FSS scores after accounting for age, waist-hip ratio and lifestyle risk factors. CONCLUSIONS: Based on these preliminary findings, there was a significant increase in SBP of female police officers after shift work, while BP and fatigue levels in all police officers were strongly related. Moreover, the predominating poor sleep quality and impact of fatigue in this sample remain a concern. Further research is required to ensure the physiological welfare of police officers, while strategies must be implemented to manage the detrimental effects shift work may be having upon their cardiovascular and sleep health. PMID- 26840325 TI - Tests of a New Drowsiness Characterization and Monitoring System Based on Ocular Parameters. AB - Drowsiness is the intermediate state between wakefulness and sleep. It is characterized by impairments of performance, which can be very dangerous in many activities and can lead to catastrophic accidents in transportation or in industry. There is thus an obvious need for systems that are able to continuously, objectively, and automatically estimate the level of drowsiness of a person busy at a task. We have developed such a system, which is based on the physiological state of a person, and, more specifically, on the values of ocular parameters extracted from images of the eye (photooculography), and which produces a numerical level of drowsiness. In order to test our system, we compared the level of drowsiness determined by our system to two references: (1) the level of drowsiness obtained by analyzing polysomnographic signals; and (2) the performance of individuals in the accomplishment of a task. We carried out an experiment in which 24 participants were asked to perform several Psychomotor Vigilance Tests in different sleep conditions. The results show that the output of our system is well correlated with both references. We determined also the best drowsiness level threshold in order to warn individuals before they reach dangerous situations. Our system thus has significant potential for reliably quantifying the level of drowsiness of individuals accomplishing a task and, ultimately, for preventing drowsiness-related accidents. PMID- 26840326 TI - Fatigue Risk Management: A Maritime Framework. AB - It is evident that despite efforts directed at mitigating the risk of fatigue through the adoption of hours of work and rest regulations and development of codes and guidelines, fatigue still remains a concern in shipping. Lack of fatigue management has been identified as a contributory factor in a number of recent accidents. This is further substantiated through research reports with shortfalls highlighted in current fatigue management approaches. These approaches mainly focus on prescriptive hours of work and rest and include an individualistic approach to managing fatigue. The expectation is that seafarers are responsible to manage and tolerate fatigue as part of their working life at sea. This attitude is an accepted part of a seafarer's role. Poor compliance is one manifest of this problem with shipboard demands making it hard for seafarers to follow hours of work and rest regulations, forcing them into this "poor compliance" trap. This makes current fatigue management approaches ineffective. This paper proposes a risk based approach and way forward for the implementation of a fatigue risk management framework for shipping, aiming to support the hours of work and rest requirements. This forms part of the work currently underway to review and update the International Maritime Organization, Guidelines on Fatigue. PMID- 26840327 TI - Does Suspected Sleep Disordered Breathing Impact on the Sleep and Performance of Firefighting Volunteers during a Simulated Fire Ground Campaign? AB - Adequate sleep is fundamental to workplace performance. For volunteer firefighters who work in safety critical roles, poor performance at work can be life threatening. Extended shifts and sleeping conditions negatively impact sleep during multi-day fire suppression campaigns. Having sleep disordered breathing (SDB) could contribute further to sleep deficits. Our aim was to investigate whether those with suspected SDB slept and performed more poorly during a fire ground simulation involving sleep restriction. Participants, n = 20 participated in a 3-day-4-night fire ground simulation. Based on oximetry desaturation index data collected during their participation, participants were retrospectively allocated to either a SDB (n = 8) or a non-SDB group (n = 12). The simulation began with an 8 h Baseline sleep (BL) followed by two nights of restricted (4 h) sleep and an 8 h recovery sleep (R). All sleeps were recorded using a standard electroencephalography (EEG) montage as well as oxygen saturation. During the day, participants completed neurobehavioral (response time, lapses and subjective fatigue) tasks. Mixed effects ANOVA were used to compare differences in sleep and wake variables. Analyses revealed a main effect of group for Total sleep (TST), REM , wake after sleep onset (WASO) and Arousals/h with the SDB group obtaining less TST and REM and greater WASO and Arousals/h. The group * night interaction was significant for N3 with the SDB group obtaining 42 min less during BL. There was a significant main effect of day for RRT, lapses and subjective fatigue and a significant day * group interaction for RRT. Overall, the SDB group slept less, experienced more disturbed sleep and had poorer response time performance, which was exacerbated by the second night of sleep restriction. This could present a safety concern, particularly during longer campaigns and is worthy of further investigation. In addition, we would recommend promotion of awareness of SDB, its symptoms and potential impact among volunteers and relevant agencies. PMID- 26840328 TI - Barriers to Walking: An Investigation of Adults in Hamilton (Ontario, Canada). AB - This study investigates perceived barriers to walking using data collected from 179 randomly-selected adults between the ages of 18 and 92 in Hamilton, Ontario, Canada. A survey (Hamilton Active Living Study) asked questions about socio demographics, walking, and barriers to walking. A series of binary logit models are estimated for twenty potential barriers to walking. The results demonstrate that different barriers are associated with different sub-groups of the population. Females, senior citizens, and those with a higher body mass index identify the most barriers to walking, while young adults, parents, driver's license owners, and bus pass owners identify the fewest barriers. Understanding who is affected by perceived barriers can help policy makers and health promotion agencies target sub-groups of the population in an effort to increase walking. PMID- 26840329 TI - Comparison of Four Ground-Level PM2.5 Estimation Models Using PARASOL Aerosol Optical Depth Data from China. AB - Satellite remote sensing is of considerable importance for estimating ground level PM2.5 concentrations to support environmental agencies monitoring air quality. However, most current studies have focused mainly on the application of MODIS aerosol optical depth (AOD) to predict PM2.5 concentrations, while PARASOL AOD, which is sensitive to fine-mode aerosols over land surfaces, has received little attention. In this study, we compared a linear regression model, a quadratic regression model, a power regression model and a logarithmic regression model, which were developed using PARASOL level 2 AOD collected in China from 18 January 2013 to 10 October 2013. We obtained R (correlation coefficient) values of 0.64, 0.63, 0.62, and 0.57 for the four models when they were cross validated with the observed values. Furthermore, after all the data were classified into six levels according to the Air Quality Index (AQI), a low level of statistical significance between the four empirical models was found when the ground-level PM2.5 concentrations were greater than 75 MUg/m3. The maximum R value was 0.44 (for the logarithmic regression model and the power model), and the minimum R value was 0.28 (for the logarithmic regression model and the power model) when the PM2.5 concentrations were less than 75 MUg/m3. We also discussed uncertainty sources and possible improvements. PMID- 26840330 TI - Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome. AB - A variety of dietary interventions has been used in the management of chronic fatigue syndrome (CFS), yet no therapeutic modality has demonstrated conclusive positive results in terms of effectiveness. The main aim of this study was to evaluate the effects of orally administered guanidinoacetic acid (GAA) on multidimensional fatigue inventory (MFI), musculoskeletal soreness, health related quality of life, exercise performance, screening laboratory studies, and the occurrence of adverse events in women with CFS. Twenty-one women (age 39.3 +/ 8.8 years, weight 62.8 +/- 8.5 kg, height 169.5 +/- 5.8 cm) who fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS were randomized in a double-blind, cross-over design, from 1 September 2014 through 31 May 2015, to receive either GAA (2.4 grams per day) or placebo (cellulose) by oral administration for three months, with a two-month wash-out period. No effects of intervention were found for the primary efficacy outcome (MFI score for general fatigue), and musculoskeletal pain at rest and during activity. After three months of intervention, participants receiving GAA significantly increased muscular creatine levels compared with the placebo group (36.3% vs. 2.4%; p < 0.01). Furthermore, changes from baseline in muscular strength and aerobic power were significantly greater in the GAA group compared with placebo (p < 0.05). Results from this study indicated that supplemental GAA can positively affect creatine metabolism and work capacity in women with CFS, yet GAA had no effect on main clinical outcomes, such as general fatigue and musculoskeletal soreness. PMID- 26840331 TI - Resveratrol Supplementation in Schizophrenia Patients: A Randomized Clinical Trial Evaluating Serum Glucose and Cardiovascular Risk Factors. AB - BACKGROUND: Patients with schizophrenia (SZ) are generally overweight or obese and have several metabolic disorders. Additionally, such patients have a lower life expectancy and the main cause of their increased mortality is cardiovascular disease (CVD). The objective of this study was to determine the efficacy of resveratrol supplementation on serum glucose and CVD risk factors in individuals with SZ. METHODS AND RESULTS: This is a four-week randomized, double-blind controlled trial (registration No.: NCT 02062190) in which 19 men with a diagnosis of SZ, aged 18 to 65, were assigned to either a resveratrol supplement group (200 mg/day) or a placebo group (200 mg/day). In short, we did not observe significant changes after resveratrol supplementation. In the placebo group, we found a significant increase in total cholesterol levels (p = 0.024) and in LDL cholesterol (p = 0.002), as well as a decrease in body fat percentage (p = 0.038). The placebo group also showed an increase in triglycerides (9.19%) and a reduction in HDL-cholesterol (4.88%). In the resveratrol group, triglycerides decreased (7.64%). CONCLUSION: In summary, oral resveratrol in reasonably low dosages (200 mg daily) brought no differences to body weight, waist circumference, glucose, and total cholesterol. It was possible to note that the lipid profile in the placebo group worsened and, although no significant differences were found, we can assume that resveratrol might prevent lipid profile damage and that the intervention affected the lipoprotein metabolism at various levels. PMID- 26840333 TI - Regulation of Expression and Evolution of Genes in Plastids of Rhodophytic Branch. AB - A novel algorithm and original software were used to cluster all proteins encoded in plastids of 72 species of the rhodophytic branch. The results are publicly available at http://lab6.iitp.ru/ppc/redline72/ in a database that allows fast identification of clusters (protein families) both by a fragment of an amino acid sequence and by a phylogenetic profile of a protein. No such integral clustering with the corresponding functions can be found in the public domain. The putative regulons of the transcription factors Ycf28 and Ycf29 encoded in the plastids were identified using the clustering and the database. A regulation of translation initiation was proposed for the ycf24 gene in plastids of certain red algae and apicomplexans as well as a regulation of a putative gene in apicoplasts of Babesia spp. and Theileria parva. The conserved regulation of the ycf24 gene expression and specificity alternation of the transcription factor Ycf28 were shown in the plastids. A phylogenetic tree of plastids was generated for the rhodophytic branch. The hypothesis of the origin of apicoplasts from the common ancestor of all apicomplexans from plastids of red algae was confirmed. PMID- 26840334 TI - Efficacy of Selected Insecticide Sprays and Aerosols against the Common Bed Bug, Cimex lectularius (Hemiptera: Cimicidae). AB - We evaluated the residual efficacy of four liquid sprays and four ready-to-use aerosols that are commonly used in the U.S. against a field-collected bed bug, Cimex lectularius L., strain with moderate resistance level to pyrethroids. The four liquid sprays were: Tandem (0.1% thiamethoxam, 0.03% lambda-cyhalothrin), Temprid SC (0.05% imidacloprid, 0.025% cyfluthrin), Transport GHP (0.05% acetamiprid, 0.06% bifenthrin), and Demand CS (0.03% lambda-cyhalothrin). The four aerosols were: Alpine (0.5% dinotefuran), Bedlam (0.4% sumithrin, 1.6% MGK 264), Bedlam Plus (0.4% sumithrin, 1% MGK 264, 0.05% imidacloprid), and Phantom (0.5% chlorfenapyr). Bed bugs were confined for 4 h to treated substrates (aged 24 h). Four substrates were tested: fabric, unpainted wood, painted wood, and vinyl. Bedlam, Demand CS, and Temprid SC resulted in <=70% mortality on all tested substrates. Among the other five products, substrate type significantly affected their residual efficacy, except for Transport GHP, which caused >=89.7% mortality regardless of the substrate. The effect of exposure time (5 min, 4 h, and 24 h) on the efficacy of Transport GHP and Phantom aerosol also was evaluated. A 4 h continuous exposure to Phantom aerosol or Transport GHP residue caused similar mortality to 24 h exposure and higher mortality than 5 min exposure. PMID- 26840335 TI - Heat Tolerance in Curraleiro Pe-Duro, Pantaneiro and Nelore Cattle Using Thermographic Images. AB - The objective of this study was to compare physiological and thermographic responses to heat stress in three breeds of cattle. Fifteen animals of each of the Nelore, Pantaneiro and Curraleiro Pe-Duro breeds, of approximately two years of age, were evaluated. Heart and respiratory rates, rectal and surface temperature of animals as well as soil temperature were recorded at 8:30 and 15:30 on six days. Variance, correlation, principal factors and canonical analyses were carried out. There were significant differences in the rectal temperature, heart and respiratory rate between breeds (p < 0.001). Nelore and Pantaneiro breeds had the highest rectal temperatures and the lowest respiratory rate (p < 0.001). Breed was also significant for surface temperatures (p < 0.05) showing that this factor significantly affected the response of the animal to heat tolerance in different ways. The Curraleiro Pe-Duro breed had the lowest surface temperatures independent of the period evaluated, with fewer animals that suffered with the climatic conditions, so this may be considered the best adapted when heat challenged under the experimental conditions. Thermography data showed a good correlation with the physiological indexes, and body area, neck and rump were the main points. PMID- 26840332 TI - Cellular Mechanisms of Ciliary Length Control. AB - Cilia and flagella are evolutionarily conserved, membrane-bound, microtubule based organelles on the surface of most eukaryotic cells. They play important roles in coordinating a variety of signaling pathways during growth, development, cell mobility, and tissue homeostasis. Defects in ciliary structure or function are associated with multiple human disorders called ciliopathies. These diseases affect diverse tissues, including, but not limited to the eyes, kidneys, brain, and lungs. Many processes must be coordinated simultaneously in order to initiate ciliogenesis. These include cell cycle, vesicular trafficking, and axonemal extension. Centrioles play a central role in both cell cycle progression and ciliogenesis, making the transition between basal bodies and mitotic spindle organizers integral to both processes. The maturation of centrioles involves a functional shift from cell division toward cilium nucleation which takes place concurrently with its migration and fusion to the plasma membrane. Several proteinaceous structures of the distal appendages in mother centrioles are required for this docking process. Ciliary assembly and maintenance requires a precise balance between two indispensable processes; so called assembly and disassembly. The interplay between them determines the length of the resulting cilia. These processes require a highly conserved transport system to provide the necessary substances at the tips of the cilia and to recycle ciliary turnover products to the base using a based microtubule intraflagellar transport (IFT) system. In this review; we discuss the stages of ciliogenesis as well as mechanisms controlling the lengths of assembled cilia. PMID- 26840336 TI - Dating Violence among High-Risk Young Women: A Systematic Review Using Quantitative and Qualitative Methods. AB - Our systematic review identified 21 quantitative articles and eight qualitative articles addressing dating violence among high risk young women. The groups of high-risk young women in this review include street-involved, justice-involved, pregnant or parenting, involved with Child Protective Services, and youth diagnosed with a mental health issue. Our meta-analysis of the quantitative articles indicated that 34% (CI = 0.24-0.45) of high-risk young women report that they have been victims of physical dating violence and 45% (CI = 0.31-0.61) of these young women report perpetrating physical dating violence. Significant moderator variables included questionnaire and timeframe. Meta-synthesis of the qualitative studies revealed that high-risk young women report perpetrating dating violence to gain power and respect, whereas women report becoming victims of dating violence due to increased vulnerability. PMID- 26840337 TI - Neural Basis of Brain Dysfunction Produced by Early Sleep Problems. AB - There is a wealth of evidence that disrupted sleep and circadian rhythms, which are common in modern society even during the early stages of life, have unfavorable effects on brain function. Altered brain function can cause problem behaviors later in life, such as truancy from or dropping out of school, quitting employment, and committing suicide. In this review, we discuss findings from several large cohort studies together with recent results of a cohort study using the marshmallow test, which was first introduced in the 1960s. This test assessed the ability of four-year-olds to delay gratification and showed how this ability correlated with success later in life. The role of the serotonergic system in sleep and how this role changes with age are also discussed. The serotonergic system is involved in reward processing and interactions with the dorsal striatum, ventral striatum, and the prefrontal cortex are thought to comprise the neural basis for behavioral patterns that are affected by the quantity, quality, and timing of sleep early in life. PMID- 26840338 TI - Efficacy and Safety of Flexible Versus Fixed Dosing Intervals of Insulin Glargine 300 U/mL in People with Type 2 Diabetes. AB - BACKGROUND: Insulin glargine 300 U/mL (Gla-300) has a more constant and prolonged action profile than insulin glargine 100 U/mL and in clinical studies is associated with similar glycemic control but less hypoglycemia. Whether its effects are altered by variability of injection time was examined in two 3-month substudies. MATERIALS AND METHODS: Eligible participants completing 6 months of optimized treatment with Gla-300 in EDITION 1 (n = 109) and EDITION 2 (n = 89), having a mean hemoglobin A1c (HbA1c) level of 7.3 % (SD 1.0 %), were randomized (1:1) to groups advised to increase variability of between-injection intervals to 24 +/- up to 3 h or to maintain fixed 24-h intervals for 3 months. Changes of HbA1c level and other efficacy and safety measures were assessed. RESULTS: In the fixed-dosing group, 64% of participants reported all intervals within the 23-25-h range, compared with 15% of those advised flexible dosing. In the fixed- and flexible-dosing groups, 12% and 41%, respectively, of between-injection intervals were outside the 23-25-h range, and 2% and 16%, respectively, were outside the 21 27-h range. Least squares mean between-group difference in HbA1c change from baseline was 0.05 % (95% confidence interval [CI], -0.13 to 0.23); for fasting plasma glucose, 2.7 mg/dL (95% CI, -9.0 to 14.4); and for daily basal insulin dose, 0.00 U/kg (95% CI, -0.02 to 0.03). Frequencies of hypoglycemia and adverse events did not differ between groups. CONCLUSIONS: The efficacy and safety of Gla 300 demonstrated in EDITION 1 and EDITION 2 are maintained in substudies when the insulin was injected up to 3 h before or after the usual time of administration. PMID- 26840339 TI - Systematic Review of Inhaled Bronchodilator and Corticosteroid Therapies in Infants with Bronchopulmonary Dysplasia: Implications and Future Directions. AB - BACKGROUND: There is much debate surrounding the use of inhaled bronchodilators and corticosteroids for infants with bronchopulmonary dysplasia (BPD). OBJECTIVE: The objective of this systematic review was to identify strengths and knowledge gaps in the literature regarding inhaled therapies in BPD and guide future research to improve long-termoutcomes. METHODS: The databases of Academic Search Complete, CINAHL, PUBMED/MEDLINE, and Scopus were searched for studies that evaluated both acute and long-term clinical outcomes related to the delivery and therapeutic efficacy of inhaled beta-agonists, anticholinergics and corticosteroids in infants with developing and/or established BPD. RESULTS: Of 181 articles, 22 met inclusion criteria for review. Five evaluated beta-agonist therapies (n = 84, weighted gestational age (GA) of 27.1(26-30) weeks, weighted birth weight (BW) of 974(843-1310) grams, weighted post menstrual age (PMA) of 34.8(28-39) weeks, and weighted age of 53(15-86) days old at the time of evaluation). Fourteen evaluated inhaled corticosteroids (n = 2383, GA 26.2(26-29) weeks, weighted BW of 853(760-1114) grams, weighted PMA of 27.0(26-31) weeks, and weighted age of 6(0-45) days old at time of evaluation). Three evaluated combination therapies (n = 198, weighted GA of 27.8(27-29) weeks, weighted BW of 1057(898-1247) grams, weighted PMA of 30.7(29-45) weeks, and age 20(10-111) days old at time of evaluation). CONCLUSION: Whether inhaled bronchodilators and inhaled corticosteroids improve long-term outcomes in BPD remains unclear. Literature regarding these therapies mostly addresses evolving BPD. There appears to be heterogeneity in treatment responses, and may be related to varying modes of administration. Further research is needed to evaluate inhaled therapies in infants with severe BPD. Such investigations should focus on appropriate definitions of disease and subject selection, timing of therapies, and new drugs, devices and delivery methods as compared to traditional methods across all modalities of respiratory support, in addition to the assessment of long-term outcomes of initial responders. PMID- 26840341 TI - Efficacy and Safety of Opioids for the Prevention of Etomidate-Induced Myoclonus: A Meta-Analysis. AB - Etomidate is a widely used hypnotic drug for induction of general anesthesia and sedation, especially in elderly patients and hemodynamically unstable patients. Myoclonus, however, is the most prominent problem during induction of anesthesia with etomidate. Many agents have been used to prevent it and opioid is one of them. This meta-analysis was to evaluate effects of opioids pretreatment for preventing etomidate-induced myoclonus. We searched the PubMed, EMBASE, and the Cochrane Library databases and published studies in English updated to September 2015. Randomized controlled trials of opioids versus placebo/control in patients were included. We evaluated the prophylactic effect of opioids on etomidate induced myoclonus. All statistical analysis was performed using RevMan 5.2 software. Nine randomized controlled trials involving 604 participants were included. The results indicated that compared with placebo/control, opioids allow more patients to experience no myoclonic movements after etomidate injection [risk ratio (RR) 2.76, 95% confidence interval (CI) 1.75-4.37, P < 0.0001]. The numbers of patients with mild myoclonus [(RR) 0.53, 95% (CI) 0.36-0.78, P = 0.001], moderate myoclonus [(RR) 0.36, 95% (CI) 0.23-0.55, P < 0.00001], and severe myoclonus [(RR) 0.20, 95% (CI) 0.08-0.52, P = 0.0009] after etomidate injection were significantly decreased with the pretreatment of opioids. This meta-analysis suggests that pretreatment with opioids before injecting etomidate was effective for preventing etomidate-induced myoclonus and can reduce the intensity of myoclonus without any adverse effects. PMID- 26840340 TI - Identification of Human Islet Amyloid Polypeptide as a BACE2 Substrate. AB - Pancreatic amyloid formation by islet amyloid polypeptide (IAPP) is a hallmark pathological feature of type 2 diabetes. IAPP is stored in the secretory granules of pancreatic beta-cells and co-secreted with insulin to maintain glucose homeostasis. IAPP is innocuous under homeostatic conditions but imbalances in production or processing of IAPP may result in homodimer formation leading to the rapid production of cytotoxic oligomers and amyloid fibrils. The consequence is beta-cell dysfunction and the accumulation of proteinaceous plaques in and around pancreatic islets. Beta-site APP-cleaving enzyme 2, BACE2, is an aspartyl protease commonly associated with BACE1, a related homolog responsible for amyloid processing in the brain and strongly implicated in Alzheimer's disease. Herein, we identify two distinct sites of the mature human IAPP sequence that are susceptible to BACE2-mediated proteolytic activity. The result of proteolysis is modulation of human IAPP fibrillation and human IAPP protein degradation. These results suggest a potential therapeutic role for BACE2 in type 2 diabetes associated hyperamylinaemia. PMID- 26840343 TI - Cannabinoids for treatment of glaucoma. AB - PURPOSE OF REVIEW: The purpose of this article is to review the current status of cannabis in the treatment of glaucoma, including the greater availability of marijuana in the USA. RECENT FINDINGS: The potency of marijuana, as measured by the concentration of Delta-tetrahydrocannabinol, has increased from ~2 to 3% in the 1970s to ~20% today. Many US states have passed laws allowing either medicinal or recreational use of marijuana. SUMMARY: The pharmacology of marijuana and its effect on intraocular pressure has not changed since the research in the 1970s and 1980s. Marijuana is an effective ocular hypotensive agent. However, cardiovascular and neurological effects are observed at the same dose, and may theoretically reduce the beneficial effect of lowering intraocular pressure by reducing ocular blood flow. The clinician must be cognizant of this potential in diagnosis, prognosis, and therapy. PMID- 26840342 TI - The Distribution of Prion Protein Allotypes Differs Between Sporadic and Iatrogenic Creutzfeldt-Jakob Disease Patients. AB - Sporadic Creutzfeldt-Jakob disease (sCJD) is the most prevalent of the human prion diseases, which are fatal and transmissible neurodegenerative diseases caused by the infectious prion protein (PrP(Sc)). The origin of sCJD is unknown, although the initiating event is thought to be the stochastic misfolding of endogenous prion protein (PrP(C)) into infectious PrP(Sc). By contrast, human growth hormone-associated cases of iatrogenic CJD (iCJD) in the United Kingdom (UK) are associated with exposure to an exogenous source of PrP(Sc). In both forms of CJD, heterozygosity at residue 129 for methionine (M) or valine (V) in the prion protein gene may affect disease phenotype, onset and progression. However, the relative contribution of each PrP(C) allotype to PrP(Sc) in heterozygous cases of CJD is unknown. Using mass spectrometry, we determined that the relative abundance of PrP(Sc) with M or V at residue 129 in brain specimens from MV cases of sCJD was highly variable. This result is consistent with PrP(C) containing an M or V at residue 129 having a similar propensity to misfold into PrP(Sc) thus causing sCJD. By contrast, PrP(Sc) with V at residue 129 predominated in the majority of the UK human growth hormone associated iCJD cases, consistent with exposure to infectious PrP(Sc) containing V at residue 129. In both types of CJD, the PrP(Sc) allotype ratio had no correlation with CJD type, age at clinical onset, or disease duration. Therefore, factors other than PrP(Sc) allotype abundance must influence the clinical progression and phenotype of heterozygous cases of CJD. PMID- 26840345 TI - Interleukin-21 Is Associated with Early Antiviral Response in Patients with Hepatitis B e Antigen-Positive Chronic Hepatitis B and Nonalcoholic Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) becomes a characteristic of liver disease. Interleukin-21 (IL-21) plays an important role in the control of chronic hepatitis B (CHB). We aimed to investigate the relationship between IL-21 and early (24 weeks) viral response (EVR) to antiviral therapy in patients with coexistence of CHB and NAFLD (CHB + NAFLD). A prospective study was carried out in hepatitis B e antigen (HBeAg)-positive CHB + NAFLD and CHB patients receiving Entecavir for initial antiviral therapy, by recording demographic, anthropometric, and clinical data at baseline 12 and 24 weeks. Univariate analysis, correlation analysis, and receiver operating characteristic curve (ROC) were applied to find related factors with EVR. Forty CHB + NAFLD patients and 20 CHB patients entered final analysis. At baseline, IL-21, triglyceride (TG), cholesterol (CHOL), glutanyltransferase (GGT), body mass index (BMI), and computed tomography (CT) ratio of liver/spleen showed significant difference between the 2 groups. Although no significant difference was found, EVR rates was lower in CHB + NAFLD than CHB (75% vs. 90%, P = 0.053). Baseline IL-21 was associated with BMI, CT ratio of liver/spleen, TG, CHOL, and HBeAg level in CHB + NAFLD patients, whose IL-21, alanine aminotransferase, aspartate aminotransferase, CHOL, BMI, and CT ratio of liver/spleen at baseline was associated with EVR. Only the level of IL-21 exhibited significant increase from 0 to 12 weeks, while the change line of other associated factors was nearly parallel between EVR group and non-EVR group. ROC discovered the level of IL-21 at 12 weeks implied a strong predictive value for EVR. We deduced that IL-21 was associated with EVR, and the elevated level of IL-21 at treatment week 12 can predict EVR in CHB + NAFLD patients. PMID- 26840346 TI - Novel Silicone-Coated 125I Seeds for the Treatment of Extrahepatic Cholangiocarcinoma. AB - 125I seeds coated with titanium are considered a safe and effective interstitial brachytherapy for tumors, while the cost of 125I seeds is a major problem for the patients implanting lots of seeds. The aim of this paper was to develop a novel silicone coating for 125I seeds with a lower cost. In order to show the radionuclide utilization ratio, the silicone was coated onto the seeds using the electro-spinning method and the radioactivity was evaluated, then the anti-tumor efficacy of silicone 125I seeds was compared with titanium 125I seeds. The seeds were divided into four groups: A (control), B (pure silicone), C (silicone 125I), D (titanium 125I) at 2 Gy or 4 Gy. Their anti-tumour activity and mechanism were assessed in vitro and in vivo using a human extrahepatic cholangiocarcinoma cell line FRH-0201 and tumor-bearing BALB/c nude mice. The silicone 125I seeds showed higher radioactivity; the rate of cell apoptosis in vitro and the histopathology in vivo demonstrated that the silicone 125I seeds shared similar anti-tumor efficacy with the titanium 125I seeds for the treatment of extrahepatic cholangiocarcinoma, while they have a much lower cost. PMID- 26840347 TI - Biological Activity of the Alternative Promoters of the Dictyostelium discoideum Adenylyl Cyclase A Gene. AB - Amoebae of the Dictyostelium discoideum species form multicellular fruiting bodies upon starvation. Cyclic adenosine monophosphate (cAMP) is used as intercellular signalling molecule in cell-aggregation, cell differentiation and morphogenesis. This molecule is synthesized by three adenylyl cyclases, one of which, ACA, is required for cell aggregation. The gene coding for ACA (acaA) is transcribed from three different promoters that are active at different developmental stages. Promoter 1 is active during cell-aggregation, promoters 2 and 3 are active in prespore and prestalk tip cells at subsequent developmental stages. The biological relevance of acaA expression from each of the promoters has been studied in this article. The acaA gene was expressed in acaA-mutant cells, that do not aggregate, under control of each of the three acaA promoters. acaA expression under promoter 1 control induced cell aggregation although subsequent development was delayed, very small fruiting bodies were formed and cell differentiation genes were expressed at very low levels. Promoter 2-driven acaA expression induced the formation of small aggregates and small fruiting bodies were formed at the same time as in wild-type strains and differentiation genes were also expressed at lower levels. Expression of acaA from promoter 3 induced aggregates and fruiting bodies formation and their size and the expression of differentiation genes were more similar to that of wild-type cells. Expression of acaA from promoters 1 and 2 in AX4 cells also produced smaller structures. In conclusion, the expression of acaA under control of the aggregation-specific Promoter 1 is able to induce cell aggregation in acaA-mutant strains. Expression from promoters 2 and 3 also recovered aggregation and development although promoter 3 induced a more complete recovery of fruiting body formation. PMID- 26840348 TI - Factors Associated with Functional Recovery among Older Intensive Care Unit Survivors. AB - RATIONALE: Most of the 1.4 million older adults who survive the intensive care unit (ICU) annually in the United States face increased disability, but little is known about those who achieve functional recovery. OBJECTIVES: Our objectives were twofold: to evaluate the incidence and time to recovery of premorbid function within 6 months of a critical illness and to identify independent predictors of functional recovery among older ICU survivors. METHODS: Potential participants included 754 persons aged 70 years or older who were evaluated monthly in 13 functional activities (1998-2012). The analytic sample included 218 ICU admissions from 186 ICU survivors. Functional recovery was defined as returning to a disability count less than or equal to the pre-ICU disability count within 6 months. Twenty-one potential predictors were evaluated for their associations with recovery. MEASUREMENTS AND MAIN RESULTS: Functional recovery was observed for 114 (52.3%) of the 218 admissions. In multivariable analysis, higher body mass index (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.03-1.12) and greater functional self-efficacy (HR, 1.05; 95% CI, 1.02-1.08), a measure of confidence in performing various activities, were associated with recovery, whereas pre-ICU impairment in hearing (HR, 0.38; 95% CI, 0.22-0.66) and vision (HR, 0.59; 95% CI, 0.37-0.95) were associated with a lack of recovery. CONCLUSIONS: Among older adults who survived an ICU admission with increased disability, pre-ICU hearing and vision impairment were strongly associated with poor functional recovery within 6 months, whereas higher body mass index and functional self-efficacy were associated with recovery. Future research is needed to evaluate whether interventions targeting these factors improve functional outcomes among older ICU survivors. PMID- 26840349 TI - Ischemic preconditioning modifies mortality and inflammatory response. AB - PURPOSE: To evaluate the effect of ischemic preconditioning on mortality, inflammatory mediators and oxidative stress after intestinal ischemia and reperfusion. METHODS: Male Wistar rats were allocated according to the period of ischemia with or without ischemic preconditioning which consist on clamping the superior mesenteric artery for 10 minutes followed by reperfusion for 10 minutes before the sustained ischemia period. Mortality was assessed in Phase 1 study, and the CINC-1, CINC-2 and MDA levels in the lungs were analyzed in Phase 2. RESULTS: Mortality was lower in the ischemic preconditioning group subjected to 90 minutes of ischemia compared to the group without ischemic preconditioning (I 90: 50% and IPC-90: 15%, p=0.018), and it was lower in the ischemic preconditioning group as a whole compared to the groups without ischemic preconditioning (IPC-14% and I=30%, p=0.006). Lower levels of MDA, CINC-1, and CINC-2 were observed in the animals that were subjected to ischemic preconditioning compared to the animals that were not (MDA: I-45=1.23 nmol/mg protein, and IPC-45=0.62 nmol/mg protein, p=0.0333; CINC-1: I-45=0.82 ng/mL and IPC-45=0.67 ng/mL, p=0.041; CINC-2: I-45=0.52 ng/mL and IPC-45=0.35 ng/mL, p=0.032). CONCLUSION: Ischemic preconditioning reduces mortality, inflammatory process and oxidative stress in rats subjected to intestinal ischemia and reperfusion. PMID- 26840350 TI - Dexmedetomidine preconditioning inhibits the long term inflammation induced by renal ischemia/reperfusion injury in rats. AB - PURPOSE: To investigate the protective effects of dexmedetomidine (Dex) against renal ischemia/reperfusion injury (IRI). METHODS: Sprague-Dawley rats were randomly divided to sham group, IRI group and Dex group. The SD rats were subjected to 45 min of ischemia followed by eight weeks of reperfusion. Prior to ischemia, rats were either treated with Dex or not. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. Immunohistochemistry was performed for CD3 T-cell infiltrates. Real-time PCR and western blot were detected for the expression of TNF-alpha, IL-1beta, ICAM-1, HMGB1 and TLR4. RESULTS: Compared with sham group, renal IRI significantly increased the serum levels of BUN and Cr. The H&E staining indicated that renal IRI resulted in obvious renal injury and immunohistochemistry found that there were more CD3 T-cell infiltrates in IRI group. Also, renal IRI upregulated the expression of TNF-alpha, IL-1beta, ICAM-1, HMGB1 and TLR4. However, all these changes were alleviated by the treatment with Dex. CONCLUSIONS: Dexmedetomidine has beneficial effects on long term inflammation induced by renal ischemia/reperfusion injury. Its mechanisms may be achieved through inhibiting the HMGB1/TLR4 pathway to exert protective effects. PMID- 26840351 TI - Remote limb ischemic post-conditioning attenuates ischemia-reperfusion injury in rat skin flapby limiting oxidative stress. AB - PURPOSE: To investigate the effect of remote ischemic post-conditioning (RIPoC) against ischemia-reperfusion (I/R) injury on flaps of rats. METHODS: Sprague Dawley rats were randomized into the Sham, Control, RIPoC1 and RIPoC2 groups. All the animals were submitted to a 5*4 cm superficial inferior epigastric artery flap. Eight hours of flap ischemia was induced and two protocols of limb RIPoC were applied. Tissue MDA level and SOD activity in 24-h reperfusion were assessed. Flap survival was assessed 7 days postoperatively. RESULTS: Compared to the Control group, the RIPoC1 group showed statistically decreased MDA level at 6 , 12-, and 24-h reperfusion (P = 0.01, P < 0.01 and P < 0.01, respectively), and statistically increased SOD activity at 12- and 24-h reperfusion (P < 0.05 and P < 0.01, respectively). Flap survival rate on the 7th day was significantly higher in the RIPoC1 group than the control group (47.9 +/- 6.4 vs . 29.4 +/- 7.1 %, P < 0.01). CONCLUSION: Three cycles of 5-min Limb remote ischemic post-conditioning rather than a single cycle of 15-min limb RIPoC has protective effect on flaps against ischemia-reperfusion injury by attenuating oxidative stress. PMID- 26840352 TI - Effect of folic acid in a modified experimental model of anorectal malformations adriamycin-induced in rats. AB - PURPOSE: To determine the effect of a single dose of adriamycin (ADR) to induce anorectal malformations (ARMs) and determine the effect of folic acid (FA) in this model. METHODS: Ten female Wistar rats were divided randomly in two groups. Group A - ADR; Group B - FA+ADR. Dams from group B received daily, since two weeks before the pregnancy to the end of pregnancy, FA (50mg/kg) by gavage. Dams from both groups received ADR (6mk/kg) by intraperitoneal injection on gestational day (GD) 8. Their fetuses were harvested by cesarean section on GD21 and were examined looking for ARMs. The thickness of anal stratified squamous epithelium (ASSE) and intestinal epithelium (IE) were analyzed. p<=0.05*. RESULTS: 81 fetuses were harvested. The number of fetuses; number of ARMs; mean (?%) (+/- SD) were determined to be, respectively: ADR - 41[29;65%(+/-37%)] versus FA+ADR - 40[04;16%(+/-36%)] (p=0.05). AMRs were significantly lower in FA+ADR group than in ADR group (p=0.05). The thickness (um) of ASSE (+/- SD) and IE (+/- SD) were measured, respectively: ADR - [25.98(+/-0.74) and 19.48(+/ 1.68)] versus FA+ADR - [24.74(+/-0.91) and 24.80(+/-0.81)] (p<0.005). The thickness of IE was significantly enlarged when FA was given (p<0.005). CONCLUSIONS: Single dose of adriamycin on D8 was able to induce anorectal malformations. Folic acid reduces the number and enlarged the IE of ARMs ADR induced. PMID- 26840353 TI - Lower energy and pulse stacking. A safer alternative for skin tightening using fractional CO2 laser. AB - PURPOSE: To evaluate the effect of different energies and stacking in skin shrinkage. METHODS: Three decreasing settings of a fractional CO2 laser were applied to the abdomen of Twenty five Wistar rats divided into three groups. Group I (n=5) was histologically evaluated for microthermal zones dimensions. Groups II and III (n=10 each) were macroscopic evaluated with freeware ImageJ for area contraction immediately and after 30 and 60 days. RESULTS: No statistical significance was found within microthermal zone histological dimensions (Group I) in all settings studied. (Ablation depth: 76.90 to 97.18um; Coagulation depth: 186.01 to 219.84 um). In Group II, macroscopic evaluation showed that all settings cause significant immediate skin contraction. The highest setting cause significant more intense tightening effect initially, contracting skin area from 258.65 to 179.09 mm2. The same pattern was observed in Group III. At 30 and 60 days, the lowest setting significantly sustained contraction. CONCLUSION: Lower fractional CO2 laser energies associated to pulse stacking could cause consistent and long lasting tissue contraction in rats. PMID- 26840354 TI - Effect of low-intensity therapeutic ultrasound on wound healing in rats subjected to third-degree burns. AB - PURPOSE: To determine the effectiveness of low-intensity therapeutic ultrasound (LITUS) on wound healing in rats with third-degree burns. METHODS: Twenty rats were divided into the Control Group that comprised four rats without third-degree burns that did not undergo LITUS, the Burned Group (BG), comprising eight rats with third-degree burns that did not undergo LITUS, and the Burned with Treatment Group (BTG), comprising eight rats with third-degree burns that were administered LITUS. LITUS began 24 h after injury and involved daily applications for 8 min at 0.1 W/cm2 for 14 days. RESULTS: The BTG lost less weight than the BG (Q=2.75; p<0.05). No visible differences were apparent among the groups' lesions on day 4. By the end of treatment, wound healing was more evident in the BTG. No statistically significant differences were found between the BG and the BTG in relation to the parameters measured using the histological changes in burn wound healing scoring system. CONCLUSION: The LITUS protocol applied to the animals with third-degree burns accelerated the formation of fibrin-leukocyte crusts and significantly reduced weight loss. However, burn wound healing was not accelerated. PMID- 26840355 TI - Expression of P53, HER2 and Ki67 proteins in rats subjected to bladder augmentation with stomach, colon and ileum. AB - PURPOSE: To study the expression of HER2, p53 and Ki67 proteins in cystoplasties. METHODS: Sixty rats were distributed randomly into three groups of 20 animals. Bladder augmentation was held to increase with ileum (Group I), colon (Group II) and stomach (Group III). Tissue samples of neobladder was collected from each rat to its own control. The animals were sacrificed after 12 weeks. The neobladder was withdrawn for immunohistochemistry analysis of p53, HER2 and Ki67 expression. Wilcoxon and Mann-Whitney tests were used for statistical study. RESULTS: There were no significant changes in the expression of p53 and HER2 proteins. It was observed significant increase (p<0.0001) in Ki67 expression in all groups, when compared with their respective controls. When the study groups were compared with each other, there was increase of cell proliferation in the largest gastrocystoplasties in respect of ileocystoplasties (p=0.004) and colocystoplasties (p=0.003). CONCLUSION: We observed significant increase of cell proliferation characterized by Ki67 protein in the digestive tract of the ileocystoplasties, the colocystoplasties and the gastrocystoplasties and this increase was significantly greater in gastrocystoplasties. PMID- 26840356 TI - The biopolymer sugarcane as filling material of critical defects in rats. AB - PURPOSE: To evaluate the effects of particulate (granule-shaped) SCB on bone repair relating it to its biocompatibility and bone neoformation. METHODS: Thirty Wistar rats were submitted to a one 7-mm-diameter defect and divided equally into three experimental groups, with two different postoperative times of evaluation, 90 and 120 days. Each calvaria defect was filled up with clot (control group), particulated autogenous bone or granulated SCB. Five animals of each group were assessed at 90 and 120 days after surgery. In these two periods, histological and histometric analysis were obtained. RESULTS: The clot group showed a bone resorption trend while the autogenous bone group a bone repair trend. However in the SCB group, the critical defect filled up only with fibrous connective tissue and presented none bone neoformation. CONCLUSION: The sugarcane biopolymer when used in critical size defects was a biocompatible material and proved to be a good material to fill bone cavities, keeping them as uniform areas filled with soft tissue and avoiding the tissue shrinkage. PMID- 26840359 TI - Sharpening the Interfaces of Axial Heterostructures in Self-Catalyzed AlGaAs Nanowires: Experiment and Theory. AB - The growth of III-III-V axial heterostructures in nanowires via the vapor-liquid solid method is deemed to be unfavorable because of the high solubility of group III elements in the catalyst droplet. In this work, we study the formation by molecular beam epitaxy of self-catalyzed GaAs nanowires with AlxGa1-xAs insertions. The composition profiles are extracted and analyzed with monolayer resolution using high-angle annular dark-field scanning transmission electron microscopy. We test successfully several growth procedures to sharpen the heterointerfaces. For a given nanowire geometry, prefilling the droplet with Al atoms is shown to be the most efficient way to reduce the width of the GaAs/AlxGa1-xAs interface. Using the thermodynamic data available in the literature, we develop numerical and analytical models of the composition profiles, showing very good agreement with experiments. These models suggest that atomically sharp interfaces are attainable for catalyst droplets of small volumes. PMID- 26840357 TI - Rabbit olfactory stem cells. Isolation protocol and characterization. AB - PURPOSE: To describe a new technique for isolation of a mesenchymal stem cells (MSCs) population from the olfactory mucosa in rabbits. METHODS: Olfactory stem cells (OSCs) were retrieved from under the cribriform plate of the Ethmoid bone. Several assays were accomplished to characterize the cell population and attest its viability in vitro. The cells were submitted to flow cytometry with the antibodies CD34, CD45, CD73, CD79, CD90 and CD105 and also they were induced to differentiate in three lineages. Functional evaluation involved analysis of in vitro growth behavior, colony forming unit like fibroblasts (CFU-f) and cryopreservation response. Further transduction with Green Fluorescent Protein (GFP) was also performed. RESULTS: The OSCs showed mesenchymal features, as positive response to CD34, CD73 and CD90 antibodies and plasticity. Additionally, these cells have high proliferated rate, and they could be cultured through many passages and kept the ability to proliferate and differentiate after cryopreservation. The positive response to the transduction signalizes the possibility of cellular tracking in vivo. This is a desirable feature in case those cells are used for pre-clinical trials. CONCLUSION: The cells harvested were mesenchymal stem cells and the technique described is therefore efficient for rabbit olfactory stem cells isolation. PMID- 26840358 TI - Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled clinical study. AB - PURPOSE: To compare the effects of magnesium sulfate and ketamine on postoperative pain and total morphine consumption in a placebo-controlled design. METHODS: One hundred and twenty women scheduled for total abdominal hysterectomy were included in this prospective, randomized, double-blind study. Postoperatively, when the Numeric Pain Rating Scale (NPRS) was four or more, IV PCA morphine was applied to all patients. The patients were randomized into three groups: Group K ketamine, Group M magnesium, and Group C saline received as infusion. Total morphine consumption for 48h, pain scores, adverse effects, and patients' satisfaction were evaluated. RESULTS: Total morphine consumption was significantly lower in Group K (32.6+/-9.2 mg) than in Group M (58.9+/-6.5 mg) and in Group C (65.7+/-8.2 mg). The satisfaction level of patients in Group K was higher than the other two groups (p<0.05). Pruritus and nausea were observed more frequently in Group C. CONCLUSION: The addition of ketamine to IV-PCA morphine reduces the total consumption of morphine without psychotic effects; however, magnesium did not influence morphine consumption. PMID- 26840360 TI - Correction to Ambipolar Phosphorene Field Effect Transistor. PMID- 26840361 TI - Transformation of Silver Nanoparticles in Sewage Sludge during Incineration. AB - Silver nanoparticles (Ag-NP) discharged into the municipal sewer system largely accumulate in the sewage sludge. Incineration and agricultural use are currently the most important strategies for sewage sludge management. Thus, the behavior of Ag-NP during sewage sludge incineration is essential for a comprehensive life cycle analysis and a more complete understanding of the fate of Ag-NP in the (urban) environment. To address the transformation of Ag-NP during sewage sludge incineration, we spiked metallic Ag(0)-NP to a pilot wastewater treatment plant and digested the sludge anaerobically. The sludge was then incinerated on a bench scale fluidized bed reactor in a series of experiments under variable conditions. Complementary results from X-ray absorption spectroscopy (XAS) and electron microscopy-energy dispersive X-ray (EM-EDX) analysis revealed that Ag(0)-NP transformed into Ag2S-NP during the wastewater treatment, in agreement with previous studies. On the basis of a principal component analysis and subsequent target testing of the XAS spectra, Ag(0) was identified as a major Ag component in the ashes, and Ag2S was clearly absent. The reformation of Ag(0)-NP was confirmed by EM-EDX. The fraction of Ag(0) of the total Ag in the ashes was quantified by linear combination fitting (LCF) of XAS spectra, and values as high as 0.8 were found for sewage sludge incinerated at 800 degrees C in a synthetic flue gas atmosphere. Low LCF totals (72% to 94%) indicated that at least one relevant reference spectrum was missing in the LCF analysis. The presence of spherical Ag-NP with a diameter of <50 nm extending into the sub-nm range was revealed by electron microscopy analyses. The rapid formation of Ag(0)-NP from Ag2S during sewage sludge incineration, as demonstrated in this study, needs to be considered in the life cycle assessment of engineered Ag-NP. PMID- 26840362 TI - Ligand-based modeling of diverse aryalkylamines yields new potent P-glycoprotein inhibitors. AB - The P-glycoprotein (P-gp) efflux pump has an important role as a natural detoxification system in many types of normal and cancer cells. P-gp is implicated in multiple drug resistance (MDR) exhibited by several types of cancer against a multitude of anticancer chemotherapeutic agents, and therefore, it is clinically validated target for cancer therapy. Accordingly, in this study we combined exhaustive pharmacophore modeling and quantitative structure-activity relationship (QSAR) analysis to explore the structural requirements for potent P gp inhibitors employing 130 known P-gp ligands. Genetic function algorithm (GFA) coupled with k nearest neighbor (kNN) or multiple linear regression (MLR) analyses were employed to build self-consistent and predictive QSAR models based on optimal combinations of pharmacophores and physicochemical descriptors. Successful pharmacophores were complemented with exclusion spheres to optimize their receiver operating characteristic curve (ROC) profiles. Optimal QSAR models and their associated pharmacophore hypotheses were validated by identification and experimental evaluation of new promising P-gp inhibitory leads retrieved from the National Cancer Institute (NCI) structural database. Several potent hits were captured. The most potent hit decreased the IC50 of doxorubicin from 0.906 to 0.190 MUM on doxorubicin resistant MCF7 cell-line. PMID- 26840363 TI - Design, synthesis and biological evaluation of 3'-benzylated analogs of 3'-epi neoponkoranol as potent alpha-glucosidase inhibitors. AB - A group of 3'-epi-neoponkoranol analogs with different hydrophobic substituents attached at 3'-position of side chain moiety were designed and synthesized in order to further improve the inhibitory activities against alpha-glucosidases. Biological evaluation of these compounds revealed that sulfonium salts attached with ortho-substituted benzyl groups showed best alpha-glucosidase inhibitory activities. The most potent compound 10i showed greater inhibitory activities than all natural products. Moreover, docking studies on 10i with ntMGAM presented a new binding mode, indicating that amino residue Asp542 should be the key interacting point for strong inhibitory activity of small molecules against alpha glucosidase enzymes. The strongest alpha-glucosidase inhibitory activity of 10i could be rationalized by van der Waals interactions between the 3'-attached substituent and particularly the ortho-substituted trifluoromethyl on benzyl group with the adjacent hydrophobic amino residues. Cytotoxicity evaluation assay demonstrated a high level of safety profile of the synthesized sulfonium salts against normal cell line. The enzyme kinetic studies showed a fully competitive inhibition of these sulfonium salts on each alpha-glucosidase. PMID- 26840364 TI - Identification of a diverse indole-2-carboxamides as a potent antileishmanial chemotypes. AB - A novel series of highly diverse indole-2-carboxamides was synthesized utilizing the isocyanide based multicomponent reaction (IMCR)-post modification approach and were identified as potential antileishmanial chemotype. Among the synthesized 18 analogues, 12 analogues exhibited better antileishmanial activity against intracellular amastigotes form of Leishmania donovani (IC50 values of 0.6-7.5 MUM) as compared to standard drugs miltefosine and sodium stibogluconate. The compounds were also non-toxic towards Vero cells. Compounds 2b, 2m and 2p with significant in vitro activity were then evaluated for their in vivo efficacy following intraperitoneal route. These three compounds at a concentration of 50 mg/kg/day for 5 consecutive days showed 70.0, 63.5 and 63.4% inhibition of Leishmania amastigotes, respectively at day 7 post treatment in hamster model of visceral leishmaniasis. PMID- 26840365 TI - New quinoline derivatives as nicotinic receptor modulators. AB - As a continuation of previous work on quinoline derivatives, which showed some preference (2-3 times) for the alpha7 with respect to alpha4beta2 acetylcholine nicotinic receptors (nAChRs), we synthesized a series of novel azabicyclic or diazabicyclic compounds carrying a quinoline or isoquinoline ring, with the aim of searching for more selective alpha7 nAChR compounds. Radioligand binding studies on alpha7* and alpha4beta2* nAChRs (rat brain homogenate) revealed one compound (7) with a 2-fold higher affinity for the alpha4beta2*-subtype, and four compounds (11, 13, 14 and 16) with at least 3-fold higher affinity for alpha7* nAChR. The most promising was 11, showing Ki~100 nM and over 10-fold selectivity for alpha7* nAChR. Compounds 7, 11, 13 and 16 at 50 MUM suppressed ion currents induced in the rat alpha4beta2 nAChR and the chimeric nAChR composed of the ligand-binding domain of the chick alpha7 and transmembrane domain of the alpha1 glycine receptor, expressed in Xenopus oocytes. Calcium imaging experiments on the human alpha7 nAChR expressed in the Neuro2a cells and potentiated by PNU 120596 confirmed the antagonistic activity for 7; on the contrary, 11, 13 and 16 were agonists with the EC50 values in the range of 1.0-1.6 MUM. Thus, the introduced modifications allowed us to enhance the selectivity of quinolines towards alpha7 nAChR and to get novel compounds with agonistic activity. PMID- 26840366 TI - Amido/ureidosubstituted benzenesulfonamides-isatin conjugates as low nanomolar/subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform XII. AB - By using a molecular hybridization approach, two series of amido/ureidosubstituted benzenesulfonamides incorporating substituted-isatin moieties were synthesized. The prepared derivatives were in vitro evaluated for their inhibitory activity against human carbonic anhydrase (hCA, EC 4.2.1.1) I, II (cytosolic) and IX, XII (transmembrane, tumor-associated) isoforms. All these isoforms were inhibited in variable degrees by the sulfonamides reported here. hCA I was inhibited with KIs in the range of 7.9-894 nM, hCA II in the range of 7.5-1645 nM (with one compound having a KI > 10 MUM); hCA IX in the range of 5.0 240 nM, whereas hCA XII in the range of 0.47-2.83 nM. As all these isoforms are involved in various pathologies, in which their inhibition can be exploited therapeutically, the derivatives reported here may represent interesting extensions to the field of CA inhibitors of the sulfonamide type. PMID- 26840367 TI - A pharmacological perspective on the use of Brazilian Red Propolis and its isolated compounds against human diseases. AB - Propolis is a complex resinous mixture collected by bees, with high medicinal, historical and economic value. The nutraceutical and pharmacological benefits of propolis have been extensively explored in several fields of medicine as an important resource for prevention and treatment of oral and systemic diseases. A relatively new type of propolis, named red propolis (in Brazil, Brazilian Red Propolis - BRP), has been arousing attention for the promising pharmacological properties of some of its isolated compounds (vestitol, neovestitol, quercetin, medicarpin, formononetin, etc). Due to a distinct chemical composition, BRP and its isolated compounds (mainly isoflavones) affect a wide range of biological targets and could have an impact against numerous diseases as an antimicrobial, anti-inflammatory and immunomodulatory, antioxidant and antiproliferative agent. In this review, we comprehensively address the main aspects related to BRP bioprospection, chemistry and therapeutic potential. Further information is provided on mechanisms of action discovered thus far as well as clinical use in humans and regulatory aspects. As of now, BRP and its isolated molecules remain a fascinating topic for further research and application in biomedical areas and dentistry. PMID- 26840368 TI - 8-Halo-substituted naphtho[2,3-b]thiophene-4,9-diones as redox-active inhibitors of keratinocyte hyperproliferation with reduced membrane-damaging properties. AB - A series of 8-chloronaphtho[2,3-b]thiophene-4,9-diones and also some 8-bromo analogues were prepared. The compounds were evaluated for their potencies to suppress keratinocyte hyperproliferation using the human keratinocyte line HaCaT as the primary test system. Structure-activity relationship studies revealed that replacement of the phenolic group of an earlier series with an 8-halogen atom retained the inhibitory potency against keratinocyte hyperproliferation with IC50 values in the submicromolar range. 8-Chloro-substitution led to inhibitors that were more potent than their bromo analogues. Concomitantly, halo-substitution eliminated membrane-damaging properties as assessed by LDH release from the cytoplasm of the keratinocytes which, in contrast, were induced by the corresponding phenolic analogues. Finally, selective compounds were characterized for their ability to participate in redox cycling to generate superoxide in enzymatic and keratinocyte-based studies. PMID- 26840369 TI - Synthesis of an inositol hexakisphosphate (IP6) affinity probe to study the interactome from a colon cancer cell line. AB - Inositol hexakisphosphate (InsP6 or IP6) is an important signalling molecule in vesicular trafficking, neurotransmission, immune responses, regulation of protein kinases and phosphatases, activation of ion channels, antioxidant functions and anticancer activities. An IP6 probe was synthesised from myo-inositol via a derivatised analogue, which was immobilised through a terminal amino group onto Dynabeads. Systematic analysis of the IP6 interactome has been performed using the IP6 affinity probe using cytosolic extracts from the LIM1215 colonic carcinoma cell line. LC/MS/MS analysis identified 77 proteins or protein complexes that bind to IP6 specifically, including AP-2 complex proteins and beta arrestins as well as a number of novel potential IP6 interacting proteins. Bioinformatic enrichment analysis of the IP6 interactome reinforced the concept that IP6 regulates a number of biological processes including cell cycle and division, signal transduction, intracellular protein transport, vesicle-mediated transport and RNA splicing. PMID- 26840370 TI - A new core gross anatomy syllabus for medicine. PMID- 26840371 TI - Sequential therapy with entecavir and peginterferon alpha in chronic hepatitis B: for many but not for all? PMID- 26840372 TI - microRNA-497 inhibits invasion and metastasis of colorectal cancer cells by targeting vascular endothelial growth factor-A. AB - OBJECTIVES: microRNAs (miRNAs), are non-coding RNAs that regulate gene expression, and are involved in tumour development. The aim of this study was to investigate microRNA-497 (miR-497) expression and its role in development of colorectal cancer (CRC). MATERIALS AND METHODS: RT-PCR was performed to detect expression of miR-497 in CRC cell lines (HCT8, LOVO, Ls-174, HCT116 and HT29) and in clinical cancer specimens. To further understand its role, we restored expression of miR-497 in the HCT116 cell line by transfection with miR-497 mimics or inhibitors. Effects of miR-497 on cell proliferation, migration and invasion of targets were also determined both in vitro and in vivo. RESULTS: miR-497 expression decreased in 34 CRC tissues compared to non-tumour tissues and in tumour cell lines. Overexpression of miR-497 did not inhibit cancer cell growth but suppressed metastasis and invasion both in vitro and in vivo. Vascular endothelial growth factor-A (VEGF-A) was confirmed to be a target of miR-497. Furthermore, we found overexpression of miR-497 altered expression of key molecules of the VEGF-A/ERK/MMP-9 signalling pathway. CONCLUSIONS: Thus our results provide evidence that miR-497 might function as a metastasis suppressor in CRC. Targeting miR-497 may provide a strategy for blocking its metastasis. PMID- 26840373 TI - Control of Relative Air Humidity as a Potential Means to Improve Hygiene on Surfaces: A Preliminary Approach with Listeria monocytogenes. AB - Relative air humidity fluctuations could potentially affect the development and persistence of pathogenic microorganisms in their environments. This study aimed to characterize the impact of relative air humidity (RH) variations on the survival of Listeria monocytogenes, a bacterium persisting on food processing plant surfaces. To assess conditions leading to the lowest survival rate, four strains of L. monocytogenes (EGDe, CCL500, CCL128, and LO28) were exposed to different RH conditions (75%, 68%, 43% and 11%) with different drying kinetics and then rehydrated either progressively or instantaneously. The main factors that affected the survival of L. monocytogenes were RH level and rehydration kinetics. Lowest survival rates between 1% and 0.001% were obtained after 3 hours of treatment under optimal conditions (68% RH and instantaneous rehydration). The survival rate was decreased under 0.001% after prolonged exposure (16h) of cells under optimal conditions. Application of two successive dehydration and rehydration cycles led to an additional decrease in survival rate. This preliminary study, performed in model conditions with L. monocytogenes, showed that controlled ambient RH fluctuations could offer new possibilities to control foodborne pathogens in food processing environments and improve food safety. PMID- 26840374 TI - Does Future Diabetes Risk Impair Current Quality of Life? A Cross-Sectional Study of Health-Related Quality of Life in Relation to the Finnish Diabetes Risk Score (FINDRISC). AB - OBJECTIVES: Present study examines the relationship between the estimated risk of developing type 2 diabetes (T2D) and health-related quality of life (HRQoL). We quantify the association between Finnish Diabetes Risk Score (FINDRISC) and HRQoL, and examine the potential use of FINDRISC as tool to evaluate HRQoL indirectly. METHODS: We conducted a cross-sectional study comprising 707 Finnish people without a diagnosis of T2D between the ages of 51 and 75 years. The risk of developing T2D was assessed using the validated and widely used FINDRISC (range 0-26 points), and quality of life was measured using two preference-based HRQoL instruments (15D and SF-6D) and one health profile instrument (SF-36). Effects of the individual FINDRISC items and demographic and clinical characteristics, such as co-morbidities, on HRQoL were studied using multivariable Tobit regression models. RESULTS: Low HRQoL was significantly and directly associated with the estimated risk of developing T2D. An approximate 4-5 point change in FINDRISC score was observed to be associated with clinically noticeable changes in the preference-based instrument HRQoL index scores. The association between HRQoL and the risk of developing T2D was also observed for most dimensions of HRQoL in all applied HRQoL instruments. Overall, old age, lack of physical activity, obesity, and history of high blood glucose were the FINDRISC factors most prominently associated with lower HRQoL. CONCLUSIONS: The findings may help the health care professionals to substantiate the possible improvement in glucose metabolism and HRQoL potentially achieved by lifestyle changes, and better convince people at high risk of T2D to take action towards healthier lifestyle habits. FINDRISC may also provide an accurate proxy for HRQoL, and thus by estimating the risk of T2D with the FINDRISC, information about patients' HRQoL may also be obtained indirectly, when it is not feasible to use HRQoL instruments. PMID- 26840376 TI - Visible Light-Promoted Decarboxylative Di- and Trifluoromethylthiolation of Alkyl Carboxylic Acids. AB - Described herein is a new and straightforward decarboxylative di- and trifluoromethylthiolation of alkyl carboxylic acids promoted by visible light. This approach enables the synthesis of biologically relevant alkyl SCF2H and SCF3 compounds from cheap and abundant carboxylic acids. The method is operationally simple, using irradiation from household light sources, and its mild reaction conditions make it tolerant of a range of functional groups. The strategy employs electrophilic phthalimide-derived di- and trifluoromethylthiolation reagents and exploits the ability of the imidyl radical to carry a radical chain. PMID- 26840375 TI - Disorganization of the splenic microanatomy in ageing mice. AB - The precise mechanisms responsible for immunosenescence still remain to be determined, however, considering the evidence that disruption of the organization of primary and secondary lymphoid organs results in immunodeficiency, we propose that this could be involved in the decline of immune responses with age. Therefore, we investigated the integrity of the splenic microarchitecture in mice of increasing age and its reorganization following immune challenge in young and old mice. Several differences in the anatomy of the spleen with age in both the immune and stromal cells were observed. There is an age-related increase in the overall size of the white pulp, which occurs primarily within the T-cell zone and is mirrored by the enlargement of the T-cell stromal area, concurrent to the distinct boundary between T cells and B cells becoming less defined in older mice. In conjunction, there appears to be a loss of marginal zone macrophages, which is accompanied by an accumulation of fibroblasts in the spleens from older animals. Furthermore, whereas the reorganization of the white pulp is resolved after several days following antigenic challenge in young animals, it remains perturbed in older subjects. All these age-related changes within the spleen could potentially contribute to the age-dependent deficiencies in functional immunity. PMID- 26840379 TI - The role of diet and nutritional supplementation in perinatal depression: a systematic review. AB - This article presents a systematic literature review on whether dietary intake influences the risk for perinatal depression, i.e. depression during pregnancy or post-partum. Such a link has been hypothesized given that certain nutrients are important in the neurotransmission system and pregnancy depletes essential nutrients. PubMed, EMBASE and CINAHL databases were searched for relevant articles until 30 May 2015. We included peer-reviewed studies of any design that evaluated whether perinatal depression is related to dietary intake, which was defined as adherence to certain diets, food-derived intake of essential nutrients or supplements. We identified 4808 studies, of which 35 fulfilled inclusion criteria: six randomized controlled trials, 12 cohort, one case-control and 16 cross-sectional studies, representing 88 051 distinct subjects. Studies were grouped into four main categories based on the analysis of dietary intake: adherence to dietary patterns (nine studies); full panel of essential nutrients (six studies); specific nutrients (including B vitamins, Vitamin D, calcium and zinc; eight studies); and intake of fish or polyunsaturated fatty acids (PUFAs; 12 studies). While 13 studies, including three PUFA supplementation trials, found no evidence of an association, 22 studies showed protective effects from healthy dietary patterns, multivitamin supplementation, fish and PUFA intake, calcium, Vitamin D, zinc and possibly selenium. Given the methodological limitations of existing studies and inconsistencies in findings across studies, the evidence on whether nutritional factors influence the risk of perinatal depression is still inconclusive. Further longitudinal studies are needed, with robust and consistent measurement of dietary intake and depressive symptoms, ideally starting before pregnancy. PMID- 26840377 TI - Commensal A4 bacteria inhibit intestinal Th2-cell responses through induction of dendritic cell TGF-beta production. AB - It has been shown that while commensal bacteria promote Th1, Th17 and Treg cells in lamina propria (LP) in steady-state conditions, they suppress mucosal Th2 cells. However, it is still unclear whether there are specific commensal organisms down-regulating Th2 responses, and the mechanism involved. Here we demonstrate that commensal A4 bacteria, a member of the Lachnospiraceae family, which produce an immunodominant microbiota CBir1 antigen, inhibits LP Th2-cell development. When transferred into the intestines of RAG(-/-) mice, CBir1 specific T cells developed predominately towards Th1 cells and Th17 cells, but to a lesser extent into Th2 cells. The addition of A4 bacterial lysates to CD4(+) T cell cultures inhibited production of IL-4. A4 bacteria stimulated dendritic cell production of TGF-beta, and blockade of TGF-beta abrogated A4 bacteria inhibition of Th2-cell development in vitro and in vivo. Collectively, our data show that A4 bacteria inhibit Th2-cell differentiation by inducing dendritic cell production of TGF-beta. PMID- 26840378 TI - Assessing the fetal effects of maternal obesity via transcriptomic analysis of cord blood: a prospective case-control study. AB - OBJECTIVE: To analyse fetal gene expression at term using umbilical cord blood, in order to provide insights into the effects of maternal obesity on human development. DESIGN: Prospective case-control study. SETTING: Academic tertiary care centre. POPULATION: Eight obese (body mass index >=30 kg/m(2)) and eight lean (body mass index <25 kg/m(2)) pregnant women undergoing prelabour caesarean delivery at term. METHODS: Women were matched for gestational age and fetal sex. Cord blood RNA was extracted and hybridised to gene expression arrays. Differentially regulated genes were identified using paired t-tests and the Benjamini-Hochberg correction. Functional analyses were performed using Ingenuity Pathway Analysis, BioGPS and Gene Set Enrichment Analysis with a fetal-specific annotation. Z-scores >=2.0 or P-values <0.01 were considered significant. MAIN OUTCOME MEASURE: Functions of differentially regulated genes in fetuses of obese women. RESULTS: A total of 701 differentially regulated genes were identified, producing an expression profile implicating neurodegeneration, decreased survival of sensory neurons, and decreased neurogenesis in the fetuses of obese women. Upstream regulators related to inflammatory signalling were significantly activated; those related to insulin receptor signalling, lipid homeostasis, regulation of axonal guidance, and cellular response to oxidative stress were significantly inhibited. Of 26 tissue-specific genes that were differentially regulated in fetuses of obese women, six mapped to the fetal brain. CONCLUSION: Maternal obesity affects fetal gene expression at term, implicating dysregulated brain development, inflammatory and immune signalling, glucose and lipid homeostasis, and oxidative stress. This may have implications for postnatal neurodevelopment and metabolism. PMID- 26840380 TI - Phrenic Nerve Injury During Isolation of the Superior Vena Cava: Prevention Using Diaphragmatic Compound Motor Action Potentials - "Primum Nil Nocere.". PMID- 26840381 TI - Apparently intrathyroid papillary thyroid carcinoma >1 and <=4 cm: is the need for completion thyroidectomy common among patients submitted to lobectomy? PMID- 26840382 TI - How anatomy should be taught: Debatable facts. PMID- 26840383 TI - Editorial Comment to Prediagnostic prostate-specific antigen kinetics and the risk of biopsy progression in active surveillance patients. PMID- 26840384 TI - Can a Welfarist Approach be Used to Justify a Moral Duty to Cognitively Enhance Children? AB - The desire to self-improve is probably as old as humanity: most of us want to be smarter, more athletic, more beautiful, or more talented. However, in the light of an ever increasing array of possibilities to enhance our capacities, clarity about the purpose and goal of such efforts becomes crucial. This is especially true when decisions are made for children, who are exposed to their parents' plans and desires for them under a notion of increasing wellbeing. In recent years, cognitive enhancement has become a popular candidate for the promotion of wellbeing; welfarists even impose a moral duty on parents to cognitively enhance their children for the sake of their wellbeing. In this article, I aim to show that welfarists are mistaken in inferring such a moral obligation from the potential benefit of cognitive enhancement. In support of this, I offer three arguments: (a) the vagueness of wellbeing as a theoretical concept means it becomes impossible to apply in practice; (b) the link between cognition and wellbeing is far from unequivocal; and (c) quantification issues with regard to cognition make a duty impossible to discharge. In conclusion, I reject the welfarist approach as a justification for a parental moral obligation to cognitively enhance children. PMID- 26840386 TI - New records of the Japanese seahorse Hippocampus mohnikei in Southeast Asia lead to updates in range, habitat and threats. AB - New records of the Japanese seahorse Hippocampus mohnikei from Cambodia, Malaysia, Thailand and Vietnam, along with recently published studies from India and Singapore, have greatly expanded the known range of H. mohnikei within Southeast Asia. These new records reveal novel habitat preferences and threats to H. mohnikei in the region. Although the global conservation status of H. mohnikei is classified as Data Deficient according to the IUCN Red List of Threatened Species, new sightings indicate that this species is found in similar habitats and faces similar threats as other Hippocampus species that are considered Vulnerable. PMID- 26840387 TI - Flexible and Stretchable Physical Sensor Integrated Platforms for Wearable Human Activity Monitoringand Personal Healthcare. AB - Flexible and stretchable physical sensors that can measure and quantify electrical signals generated by human activities are attracting a great deal of attention as they have unique characteristics, such as ultrathinness, low modulus, light weight, high flexibility, and stretchability. These flexible and stretchable physical sensors conformally attached on the surface of organs or skin can provide a new opportunity for human-activity monitoring and personal healthcare. Consequently, in recent years there has been considerable research effort devoted to the development of flexible and stretchable physical sensors to fulfill the requirements of future technology, and much progress has been achieved. Here, the most recent developments of flexible and stretchable physical sensors are described, including temperature, pressure, and strain sensors, and flexible and stretchable sensor-integrated platforms. The latest successful examples of flexible and stretchable physical sensors for the detection of temperature, pressure, and strain, as well as their novel structures, technological innovations, and challenges, are reviewed first. In the next section, recent progress regarding sensor-integrated wearable platforms is overviewed in detail. Some of the latest achievements regarding self-powered sensor-integrated wearable platform technologies are also reviewed. Further research direction and challenges are also proposed to develop a fully sensor integrated wearable platform for monitoring human activity and personal healthcare in the near future. PMID- 26840388 TI - Total robotic radical rectal resection with da Vinci Xi system: single docking, single phase technique. AB - OBJECTIVE: This study aims to assess the advantages of Da Vinci Xi system in rectal cancer surgery. It also assesses the initial oncological outcomes after rectal resection with this system from a tertiary cancer center in India. INTRODUCTION: Robotic rectal surgery has distinct advantages over laparoscopy. Total robotic resection is increasing following the evolution of hybrid technology. The latest Da Vinci Xi system (Intuitive Surgical, Sunnyvale, USA) is enabled with newer features to make total robotic resection possible with single docking and single phase. METHODS AND RESULTS: Thirty-six patients underwent total robotic resection in a single phase and single docking. We used newer port positions in a straight line. Median distance from the anal verge was 4.5 cm. Median robotic docking time and robotic procedure time were 9 and 280 min, respectively. Median blood loss was 100 mL. One patient needed conversion to an open approach due to advanced disease. Circumferential resection margin and longitudinal resection margins were uninvolved in all other patients. Median lymph node yield was 10. Median post-operative stay was 7 days. There were no intra-operative adverse events. CONCLUSION: The latest Da Vinci Xi system has made total robotic rectal surgery feasible in single docking and single phase. With the new system, four arm total robotic rectal surgery may replace the hybrid technique of laparoscopic and robotic surgery for rectal malignancies. The learning curve for the new system appears to be shorter than anticipated. Early perioperative and oncological outcomes of total robotic rectal surgery with the new system are promising. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26840389 TI - Association between the Density of Physicians and Suicide Rates in Japan: Nationwide Ecological Study Using a Spatial Bayesian Model. AB - BACKGROUND: Regional disparity in suicide rates is a serious problem worldwide. One possible cause is unequal distribution of the health workforce, especially psychiatrists. Research about the association between regional physician numbers and suicide rates is therefore important but studies are rare. The objective of this study was to evaluate the association between physician numbers and suicide rates in Japan, by municipality. METHODS: The study included all the municipalities in Japan (n = 1,896). We estimated smoothed standardized mortality ratios of suicide rates for each municipality and evaluated the association between health workforce and suicide rates using a hierarchical Bayesian model accounting for spatially correlated random effects, a conditional autoregressive model. We assumed a Poisson distribution for the observed number of suicides and set the expected number of suicides as the offset variable. The explanatory variables were numbers of physicians, a binary variable for the presence of psychiatrists, and social covariates. RESULTS: After adjustment for socioeconomic factors, suicide rates in municipalities that had at least one psychiatrist were lower than those in the other municipalities. There was, however, a positive and statistically significant association between the number of physicians and suicide rates. CONCLUSIONS: Suicide rates in municipalities that had at least one psychiatrist were lower than those in other municipalities, but the number of physicians was positively and significantly related with suicide rates. To improve the regional disparity in suicide rates, the government should encourage psychiatrists to participate in community-based suicide prevention programs and to settle in municipalities that currently have no psychiatrists. The government and other stakeholders should also construct better networks between psychiatrists and non-psychiatrists to support sharing of information for suicide prevention. PMID- 26840390 TI - Concise Review: When Colonies Are Not Clones: Evidence and Implications of Intracolony Heterogeneity in Mesenchymal Stem Cells. AB - The emergence of heterogeneity in putative mesenchymal stem cell (MSC) populations during in vitro expansion is not appreciated fully by the various communities who study, engineer, and use such stem cells. However, this functional diversity holds direct implications for basic research and therapeutic applications of MSCs that require predictable phenotypic function and efficacy. Despite numerous clinical trials pursuing MSC therapies, the in vitro expansion of homogeneous populations to therapeutically relevant quantities remains an elusive goal. Variation in MSC cultures has been noted not only among donors and within populations expanded from the same donor, but also debatably within single cell-derived colonies. The potential for even intracolony heterogeneity suggests that any purified subpopulation will inevitably become heterogeneous upon further expansion under current culture conditions. Here, we review the noted or retrospective evidence of intracolony MSC heterogeneity, to facilitate discussion of its possible causes and potential solutions to its mitigation. This analysis suggests that functional diversity within an MSC colony must be considered in design of experiments and trials for even nonclonal stem cell populations, and can be mitigated or even exploited when the mechanisms of onset are better understood. Stem Cells 2016;34:1135-1141. PMID- 26840392 TI - Prognostic impact of the number of retrieved lymph nodes in patients with gastric cancer. AB - BACKGROUND: In gastric cancer, although at least 16 lymph nodes of retrieved lymph nodes (RLNs) are recommended for nodal staging in Japanese Classification of Gastric Carcinoma and TNM classifications, we wished to clarify their appropriateness. STUDY DESIGN: A total of 1289 consecutive gastric cancer patients, who underwent gastrectomy between 1997 and 2011, were analyzed retrospectively. RESULTS: (i) The patients were divided into two groups using a cut-off RLN number of 16 (RLN < 16 or RLN >= 16). There were significant differences in the survival rates of patients in pStage II (P < 0.0001) and III (P = 0.0009), but not those of patients in pStage I (P = 0.0627) and IV (P = 0.1553). (ii) In 498 consecutive patients in pStage II and III, compared with patients in the RLN >= 16 group, those in the RLN < 16 group had a significantly higher incidence of older age (P = 0.0004) and positive lymph node ratio (PLNR) (P < 0.0001). Univariate and multivariate analyses showed that an RLN number of less than 16 was an independent poor prognostic factor (P < 0.0001, HR 2.48 [95% CI: 1.60-3.70]). (iii) A cut-off RLN number of 16 could cause the stage migration effect in pStage II or III patients. A cut-off RLN number of 25 or more could eliminate the prognostic effect. CONCLUSION: The RLN number may potentially affect the prognosis and the stage migration in pStage II or III gastric cancer patients. An RLN number of 25 or more could be sufficient for nodal staging. PMID- 26840391 TI - Quantifying disease progression in amyotrophic lateral sclerosis using peripheral nerve sonography. AB - INTRODUCTION: In this study we investigated whether peripheral nerve sonography could be used as a biomarker to monitor disease progression in amyotrophic lateral sclerosis (ALS). METHODS: In 37 patients, ulnar and median nerve cross sectional area (CSA) was determined in at least 2 ultrasound sessions; mean follow-up was 14.5 months. Linear mixed-effects models were conducted to analyze time effects on CSA. RESULTS: Ulnar nerve CSA declined significantly at a monthly rate of -0.04 mm(2) (forearm) and -0.05 mm(2) (wrist); the decrease was more pronounced when baseline CSA was greater. To detect a 50% treatment effect on ulnar nerve CSA, 332 patients would need to be entered in a hypothetical randomized, controlled clinical trial. Time had no significant impact on median nerve CSA. CONCLUSIONS: Distal ulnar nerve ultrasound may be a useful biomarker to monitor disease progression in ALS, especially as hypothetical treatment effects on CSA seem to be detectable in manageable cohort sizes. Muscle Nerve 54: 391-397, 2016. PMID- 26840393 TI - Research on cruciferous vegetables, indole-3-carbinol, and cancer prevention: A tribute to Lee W. Wattenberg. AB - Lee W. Wattenberg, who spent his entire career at the University of Minnesota, was a true pioneer in the field of chemoprevention. This paper is a tribute to his groundbreaking research which uncovered the cancer prevention properties of many dietary compounds, including those discussed here in some detail-indole-3 carbinol and diindolylmethane. These compounds occur as glucosinolate conjugates in cruciferous vegetables and are released when one chews or otherwise macerates the vegetable. They have numerous beneficial effects including the ability to prevent cancer in laboratory animals treated with carcinogens. We review some of the early work on indole-3-carbinol and diindolylmethane which spurred subsequent studies on their efficacy and molecular mechanisms of prevention. We also present unique data on field conditions that affect levels of their glucosinolate precursors in vegetables and on the release of diindolylmethane in people who consume cruciferous vegetables. PMID- 26840394 TI - The Effect of Social Parasitism by Polyergus breviceps on the Nestmate Recognition System of Its Host, Formica altipetens. AB - Highly social ants, bees and wasps employ sophisticated recognition systems to identify colony members and deny foreign individuals access to their nest. For ants, cuticular hydrocarbons serve as the labels used to ascertain nest membership. Social parasites, however, are capable of breaking the recognition code so that they can thrive unopposed within the colonies of their hosts. Here we examine the influence of the socially parasitic slave-making ant, Polyergus breviceps on the nestmate recognition system of its slaves, Formica altipetens. We compared the chemical, genetic, and behavioral characteristics of colonies of enslaved and free-living F. altipetens. We found that enslaved Formica colonies were more genetically and chemically diverse than their free-living counterparts. These differences are likely caused by the hallmark of slave-making ant ecology: seasonal raids in which pupa are stolen from several adjacent host colonies. The different social environments of enslaved and free-living Formica appear to affect their recognition behaviors: enslaved Formica workers were less aggressive towards non-nestmates than were free-living Formica. Our findings indicate that parasitism by P. breviceps dramatically alters both the chemical and genetic context in which their kidnapped hosts develop, leading to changes in how they recognize nestmates. PMID- 26840396 TI - Association between Potentially Inappropriate Medication (PIM) Use and Risk of Hospitalization in Older Adults: An Observational Study Based on Routine Data Comparing PIM Use with Use of PIM Alternatives. AB - OBJECTIVE: The safety of potentially inappropriate medications (PIMs) in elderly patients is still debated. Using the PRISCUS list, we examined the incident all cause hospitalization risk associated with PIMs compared to PIM alternatives during the 180 days post individual first pharmacy dispensing (index date). METHODS: Routine claims data from a German health insurer on 392,337 ambulatory patients aged >=65 years, were used to estimate adjusted hazard ratios (HRs) for hospitalization associated with incident PIM use. Observation period was January 2009 -December 2010. Users of PIM alternatives, as defined by the PRISCUS list, were the reference group. Patients with PIM dispensing or hospital stay in a six month "washout" period (second half of 2008) were excluded. All potential confounders were determined in the half year before the individual index date. RESULTS: In the total cohort 60.7% were female. Median age was 73 years. Of 79,041 incident PIM users, 58.4% had PIMs dispensed in one quarter of 2009 or 2010, 19.3% in two quarters, and 22.3% in three or more quarters. There were 126,535 hospitalizations during the observation period, and 47,470 of them occurred within 180 days post first dispensing. Multivariable Cox regression analysis revealed PIM use as a significant risk factor for hospitalization (HR 1.378; 95% CI 1.349-1.407) compared to use of PIM alternatives. CONCLUSIONS: PIM use compared to use of PIM alternatives is associated with an increased risk of all-cause hospitalization in the 180 days following individual index date. Future analyses comparing a single PIM with its corresponding alternative may help identify those PIMs responsible for this. PMID- 26840395 TI - Clinical characteristics and outcomes in biclonal gammopathies. AB - A single monoclonal protein typically characterizes monoclonal gammopathies, but a small proportion may have more than one M protein identifiable. In the setting of symptomatic multiple myeloma (MM), the development of a new monoclonal protein following therapy is associated with better outcomes. As for the precursor conditions, monoclonal gammopathy undetermined significance (MGUS) and smoldering multiple myeloma (SMM), there is limited information on the impact of a second monoclonal protein on the disease course, including progression and response to treatment. The outcomes of patients with MGUS and SMM with more than one monoclonal protein, after identifying 539 patients with biclonal proteins on electrophoresis and/or immunofixation, were reported. About 22 of 393 patients with MGUS/biclonal gammopathy of undetermined significance (BGUS) progressed to SMM (6), MM (11), AL (3), or WM (2), and 5 of 16 patients with biclonal SMM progressed to MM. The rate of progression for BGUS was approximately 1% per year, which is similar to MGUS with one monoclonal protein. The median estimated time of progression of biclonal SMM was 2.6 years; similar to monoclonal SMM. For patients with biclonal MM, both M spikes responded to treatment and, upon relapse, the original dominant M protein remained dominant as the disease progressed. In conclusion, the presence of a second monoclonal protein does not appear to affect the progression of precursor states and suggests multiple monoclonal proteins do not clinically impact one another in the course of the disease. PMID- 26840397 TI - Modeling the Cost Effectiveness of Neuroimaging-Based Treatment of Acute Wake-Up Stroke. AB - BACKGROUND: Thrombolytic treatment (tissue-type plasminogen activator [tPA]) is only recommended for acute ischemic stroke patients with stroke onset time <4.5 hours. tPA is not recommended when stroke onset time is unknown. Diffusion weighted MRI (DWI) and fluid attenuated inversion recovery (FLAIR) MRI mismatch information has been found to approximate stroke onset time with some accuracy. Therefore, we developed a micro-simulation model to project health outcomes and costs of MRI-based treatment decisions versus no treatment for acute wake-up stroke patients. METHODS AND FINDINGS: The model assigned simulated patients a true stroke onset time from a specified probability distribution. DWI-FLAIR mismatch estimated stroke onset <4.5 hours with sensitivity and specificity of 0.62 and 0.78, respectively. Modified Rankin Scale (mRS) scores reflected tPA treatment effectiveness accounting for patients' true stroke onset time. Discounted lifetime costs and benefits (quality-adjusted life years [QALYs]) were projected for each strategy. Incremental cost-effectiveness ratios (ICERs) were calculated for the MRI-based strategy in base-case and sensitivity analyses. With no treatment, 45.1% of simulated patients experienced a good stroke outcome (mRS score 0-1). Under the MRI-based strategy, in which 17.0% of all patients received tPA despite stroke onset times >4.5 hours, 46.3% experienced a good stroke outcome. Lifetime discounted QALYs and costs were 5.312 and $88,247 for the no treatment strategy and 5.342 and $90,869 for the MRI-based strategy, resulting in an ICER of $88,000/QALY. Results were sensitive to variations in patient- and provider-specific factors such as sleep duration, hospital travel and door-to needle times, as well as onset probability distribution, MRI specificity, and mRS utility values. CONCLUSIONS: Our model-based findings suggest that an MRI-based treatment strategy for this population could be cost-effective and quantifies the impact that patient- and provider-specific factors, such as sleep duration, hospital travel and door-to-needle times, could have on the optimal decision for wake-up stroke patients. PMID- 26840399 TI - Acceleration Data Reveal Highly Individually Structured Energetic Landscapes in Free-Ranging Fishers (Pekania pennanti). AB - Investigating animal energy expenditure across space and time may provide more detailed insight into how animals interact with their environment. This insight should improve our understanding of how changes in the environment affect animal energy budgets and is particularly relevant for animals living near or within human altered environments where habitat change can occur rapidly. We modeled fisher (Pekania pennanti) energy expenditure within their home ranges and investigated the potential environmental and spatial drivers of the predicted spatial patterns. As a proxy for energy expenditure we used overall dynamic body acceleration (ODBA) that we quantified from tri-axial accelerometer data during the active phases of 12 individuals. We used a generalized additive model (GAM) to investigate the spatial distribution of ODBA by associating the acceleration data to the animals' GPS-recorded locations. We related the spatial patterns of ODBA to the utilization distributions and habitat suitability estimates across individuals. The ODBA of fishers appears highly structured in space and was related to individual utilization distribution and habitat suitability estimates. However, we were not able to predict ODBA using the environmental data we selected. Our results suggest an unexpected complexity in the space use of animals that was only captured partially by re-location data-based concepts of home range and habitat suitability. We suggest future studies recognize the limits of ODBA that arise from the fact that acceleration is often collected at much finer spatio-temporal scales than the environmental data and that ODBA lacks a behavioral correspondence. Overcoming these limits would improve the interpretation of energy expenditure in relation to the environment. PMID- 26840398 TI - Comparative Experimental Infection Study in Dogs with Ehrlichia canis, E. chaffeensis, Anaplasma platys and A. phagocytophilum. AB - Dogs acquire infections with the Anaplasmataceae family pathogens, E. canis, E. chaffeensis, E. ewingii, A. platys and A. phagocytophilum mostly during summer months when ticks are actively feeding on animals. These pathogens are also identified as causing diseases in people. Despite the long history of tick-borne diseases in dogs, much remains to be defined pertaining to the clinical and pathological outcomes of infections with these pathogens. In the current study, we performed experimental infections in dogs with E. canis, E. chaffeensis, A. platys and A. phagocytophilum. Animals were monitored for 42 days to evaluate infection-specific clinical, hematological and pathological differences. All four pathogens caused systemic persistent infections detectible throughout the 6 weeks of infection assessment. Fever was frequently detected in animals infected with E. canis, E. chaffeensis, and A. platys, but not in dogs infected with A. phagocytophilum. Hematological differences were evident in all four infected groups, although significant overlap existed between the groups. A marked reduction in packed cell volume that correlated with reduced erythrocytes and hemoglobin was observed only in E. canis infected animals. A decline in platelet numbers was common with E. canis, A. platys and A. phagocytophilum infections. Histopathological lesions in lung, liver and spleen were observed in all four groups of infected dogs; infection with E. canis had the highest pathological scores, followed by E. chaffeensis, then A. platys and A. phagocytophilum. All four pathogens induced IgG responses starting on day 7 post infection, which was predominantly comprised of IgG2 subclass antibodies. This is the first detailed investigation comparing the infection progression and host responses in dogs after inoculation with four pathogens belonging to the Anaplasmataceae family. The study revealed a significant overlap in clinical, hematological and pathological changes resulting from the infections. PMID- 26840400 TI - Amblyceps waikhomi, a New Species of Catfish (Siluriformes: Amblycipitidae) from the Brahmaputra Drainage of Arunachal Pradesh, India. AB - Amblyceps waikhomi sp. nov. is described from the Nongkon stream which drains into the Noa Dehing River, a tributary of the Brahmaputra River, in Arunachal Pradesh, India. The new species can be distinguished from congeners (except A. torrentis) in having a deeper body depth at anus. It further differs from congeners (except A. mangois and A. serratum) in having fewer vertebrae, from A. mangois in lacking (vs. having) strongly-developed projections on the proximal lepidotrichia of the median caudal-fin rays, and in having a longer, wider, and deeper head; and from A. serratum in having a posteriorly smooth (vs. with 4-5 serrations) pectoral spine, and unequal jaw length (lower jaw longer and weakly projecting anteriorly vs. equal upper and lower jaws). It additionally differs from A. murraystuarti, A. torrentis, A. apangi, A. laticeps, and A. cerinum in having a deeply forked (vs. emarginate or truncate) caudal fin. This species is the seventh amblycipitid species known to occur in the Ganga-Brahmaputra River system. PMID- 26840401 TI - Ramentaceone, a Naphthoquinone Derived from Drosera sp., Induces Apoptosis by Suppressing PI3K/Akt Signaling in Breast Cancer Cells. AB - The phosphoinositide 3-kinase (PI3K) signaling pathway plays an important role in processes critical for breast cancer progression and its upregulation confers increased resistance of cancer cells to chemotherapy and radiation. The present study aimed at determining the activity of ramentaceone, a constituent of species in the plant genera Drosera, toward breast cancer cells and defining the involvement of PI3K/Akt inhibition in ramentaceone-mediated cell death induction. The results showed that ramentaceone exhibited high antiproliferative activity toward breast cancer cells, in particular HER2-overexpressing breast cancer cells. The mode of cell death induced by ramentaceone was through apoptosis as determined by cytometric analysis of caspase activity and Annexin V staining. Apoptosis induction was found to be mediated by inhibition of PI3K/Akt signaling and through targeting its downstream anti-apoptotic effectors. Ramentaceone inhibited PI3-kinase activity, reduced the expression of the PI3K protein and inhibited the phosphorylation of the Akt protein in breast cancer cells. The expression of the anti-apoptotic Bcl-2 protein was decreased and the levels of the pro-apoptotic proteins, Bax and Bak, were elevated. Moreover, inhibition of PI3K and silencing of Akt expression increased the sensitivity of cells to ramentaceone-induced apoptosis. In conclusion, our results indicate that ramentaceone induces apoptosis in breast cancer cells through PI3K/Akt signaling inhibition. These findings suggest further investigation of ramentaceone as a potential therapeutic agent in breast cancer therapy, in particular HER2-positive breast cancer. PMID- 26840402 TI - Picosecond Pulse Radiolysis of Propylene Carbonate as a Solute in Water and as a Solvent. AB - The ester propylene carbonate (PC) is a solvent with a high static dielectric constant where the charges generated by ionizing radiation are expected to be long-lived at room temperature. Time-resolved optical absorption spectroscopy after picosecond electron pulses reveals the formation of a UV band, within less than two nanoseconds, that is assigned to the radical anion PC(-*), arising from a fast attachment reaction of electrons onto PC. Assignment and reactivity of PC( *) in neat solvent and solutions are discussed in relation with data obtained in solutions of PC in water under reducing or oxidizing conditions and in solutions in PC of aromatic scavengers with various reduction potentials. The fate of the electrons and the ionization yield in PC are compared with those of other solvents. PMID- 26840403 TI - Interleukin-6 Is a Risk Factor for Atrial Fibrillation in Chronic Kidney Disease: Findings from the CRIC Study. AB - Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with chronic kidney disease (CKD). In this study, we examined the association between inflammation and AF in 3,762 adults with CKD, enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. AF was determined at baseline by self-report and electrocardiogram (ECG). Plasma concentrations of interleukin(IL)-1, IL-1 Receptor antagonist, IL-6, tumor necrosis factor (TNF)-alpha, transforming growth factor-beta, high sensitivity C-Reactive protein, and fibrinogen, measured at baseline. At baseline, 642 subjects had history of AF, but only 44 had AF in ECG recording. During a mean follow-up of 3.7 years, 108 subjects developed new-onset AF. There was no significant association between inflammatory biomarkers and past history of AF. After adjustment for demographic characteristics, comorbid conditions, laboratory values, echocardiographic variables, and medication use, plasma IL-6 level was significantly associated with presence of AF at baseline (Odds ratio [OR], 1.61; 95% confidence interval [CI], 1.21 to 2.14; P = 0.001) and new-onset AF (OR, 1.25; 95% CI, 1.02 to 1.53; P = 0.03). To summarize, plasma IL-6 level is an independent and consistent predictor of AF in patients with CKD. PMID- 26840404 TI - Expression of Streptococcus pneumoniae Bacteriocins Is Induced by Antibiotics via Regulatory Interplay with the Competence System. AB - Pneumococcal bacteriocins (pneumocins) are antibacterial toxins that mediate intra-species competition within the human host. However, the triggers of pneumocin expression are poorly understood. Using RNA-sequencing, we mapped the regulon of the pneumocin cluster (blp) of Streptococcus pneumoniae D39. Furthermore, by analogy with pneumococcal competence, we show that several antibiotics activate the blp-genes. Using real-time gene expression measurements we show that while the promoter driving expression of the two-component regulatory system blpR/H is constitutive, the remaining blp-promoters that control pneumocin expression, immunity and the inducer peptide BlpC, are pH dependent and induced in the late exponential phase. Intriguingly, competence for genetic transformation, mediated by the paralogous ComD/E two-component quorum system, is induced by the same environmental cues. To test for interplay between these regulatory systems, we quantified the regulatory response to the addition of synthetic BlpC and competence-stimulating peptide (CSP). Supporting the idea of such interplay, we found that immediately upon addition of CSP, the blp promoters were activated in a comD/E-dependent manner. After a delay, blp expression was highly induced and was strictly dependent on blpRH and blpC. This raised the question of the mechanism of BlpC export, since bioinformatic analysis showed that the genes encoding the putative exporter for BlpC, blpAB, are not intact in strain D39 and most other strains. By contrast, all sequenced pneumococcal strains contain intact comAB genes, encoding the transport system for CSP. Consistent with the idea that comAB mediate BlpC export, we finally show that high-level expression of the blp-genes requires comAB. Together, our results demonstrate that regulation of pneumocin expression is intertwined with competence, explaining why certain antibiotics induce blp-expression. Antibiotic induced pneumocin expression might therefore have unpredictable consequences on pneumococcal colonization dynamics by activating genes that mediate intra specific interference competition. PMID- 26840406 TI - Cadmium toxicity investigated at the physiological and biophysical levels under environmentally relevant conditions using the aquatic model plant Ceratophyllum demersum. AB - Cadmium (Cd) is an important environmental pollutant and is poisonous to most organisms. We aimed to unravel the mechanisms of Cd toxicity in the model water plant Ceratophyllum demersum exposed to low (nM) concentrations of Cd as are present in nature. Experiments were conducted under environmentally relevant conditions, including nature-like light and temperature cycles, and a low biomass to water ratio. We measured chlorophyll (Chl) fluorescence kinetics, oxygen exchange, the concentrations of reactive oxygen species and pigments, metal binding to proteins, and the accumulation of starch and metals. The inhibition threshold concentration for most parameters was 20 nM. Below this concentration, hardly any stress symptoms were observed. The first site of inhibition was photosynthetic light reactions (the maximal quantum yield of photosystem II (PSII) reaction centre measured as Fv /Fm , light-acclimated PSII activity PhiPSII , and total Chl). Trimers of the PSII light-harvesting complexes (LHCIIs) decreased more than LHC monomers and detection of Cd in the monomers suggested replacement of magnesium (Mg) by Cd in the Chl molecules. As a consequence of dysfunctional photosynthesis and energy dissipation, reactive oxygen species (superoxide and hydrogen peroxide) appeared. Cadmium had negative effects on macrophytes at much lower concentrations than reported previously, emphasizing the importance of studies applying environmentally relevant conditions. A chain of inhibition events could be established. PMID- 26840405 TI - An Optical Section-Assisted In Vivo Rabbit Model for Capsular Bend and Posterior Capsule Opacification Investigation. AB - PURPOSE: To establish an optical section-assisted in vivo rabbit model for capsular bend and posterior capsule opacification (PCO) investigation. METHODS: A total of 10 rabbits underwent phacoemulsification surgery and intraocular lens (IOL) implantation. On the basis of the relationship between the anterior capsule and IOL, the rabbits were divided into complete overlap and incomplete overlap groups, in which six and four rabbits were included, respectively. The capsular bend optical sections were assessed using ultra-long scan depth optical coherence tomography (UL-OCT), and posterior capsule opacification was evaluated with slit lamp on postoperative day 3, 7, 14, and 28. In addition, histopathological section was used to verify the accuracy of capsular bend type captured by OCT in three rabbits. RESULTS: Based on the special animal model, six capsular bend types were observed, namely, anterior (A), middle (M), posterior (P), detachment (D), funnel (Fun) and furcate adhesion (Fur). On day 3, capsular bend began to form. On 14 days, the capsular bends were comprised of A, M and D types, which were almost maintained until day 28. Histopathological section findings were consistent with optical sectioning results. In the incomplete and complete groups, the earliest PCO within the optical zone were on day 7 and 28, respectively. The incomplete group exhibited higher incidence and faster PCO on day 7 (p = 0.038) and 14 (p = 0.002). CONCLUSIONS: This animal model not only mimics capsular bend evolution and PCO processes but also produces OCT optical section images equivalent to and more repeatable than histopathology, thereby providing a promising method for the further investigations of PCO. PMID- 26840407 TI - Neisseria meningitidis Translation Elongation Factor P and Its Active-Site Arginine Residue Are Essential for Cell Viability. AB - Translation elongation factor P (EF-P), a ubiquitous protein over the entire range of bacterial species, rescues ribosomal stalling at consecutive prolines in proteins. In Escherichia coli and Salmonella enterica, the post-translational beta-lysyl modification of Lys34 of EF-P is important for the EF-P activity. The beta-lysyl EF-P modification pathway is conserved among only 26-28% of bacteria. Recently, it was found that the Shewanella oneidensis and Pseudomonas aeruginosa EF-P proteins, containing an Arg residue at position 32, are modified with rhamnose, which is a novel post-translational modification. In these bacteria, EF P and its Arg modification are both dispensable for cell viability, similar to the E. coli and S. enterica EF-P proteins and their Lys34 modification. However, in the present study, we found that EF-P and Arg32 are essential for the viability of the human pathogen, Neisseria meningitidis. We therefore analyzed the modification of Arg32 in the N. meningitidis EF-P protein, and identified the same rhamnosyl modification as in the S. oneidensis and P. aeruginosa EF-P proteins. N. meningitidis also has the orthologue of the rhamnosyl modification enzyme (EarP) from S. oneidensis and P. aeruginosa. Therefore, EarP should be a promising target for antibacterial drug development specifically against N. meningitidis. The pair of genes encoding N. meningitidis EF-P and EarP suppressed the slow-growth phenotype of the EF-P-deficient mutant of E. coli, indicating that the activity of N. meningitidis rhamnosyl-EF-P for rescuing the stalled ribosomes at proline stretches is similar to that of E. coli beta-lysyl-EF-P. The possible reasons for the unique requirement of rhamnosyl-EF-P for N. meningitidis cells are that more proline stretch-containing proteins are essential and/or the basal ribosomal activity to synthesize proline stretch-containing proteins in the absence of EF-P is lower in this bacterium than in others. PMID- 26840408 TI - Regulation of Nuclear Receptor Nur77 by miR-124. AB - The nuclear receptor Nur77 is commonly upregulated in adult cancers and has oncogenic functions. Nur77 is an immediate-early response gene that acts as a transcription factor to promote proliferation and protect cells from apoptosis. Conversely, Nur77 can translocate to the mitochondria and induce apoptosis upon treatment with various cytotoxic agents. Because Nur77 is upregulated in cancer and may have a role in cancer progression, it is of interest to understand the mechanism controlling its expression. MicroRNAs (miRNAs) are responsible for inhibiting translation of their target genes by binding to the 3'UTR and either degrading the mRNA or preventing it from being translated into protein, thereby making these non-coding endogenous RNAs vital regulators of every cellular process. Several miRNAs have been predicted to target Nur77; however, strong evidence showing the regulation of Nur77 by any miRNA is lacking. In this study, we used a luciferase reporter assay containing the 3'UTR of Nur77 to screen 296 miRNAs and found that miR-124, which is the most abundant miRNA in the brain and has a role in promoting neuronal differentiation, caused the greatest reduction in luciferase activity. Interestingly, we discovered an inverse relationship in Daoy medulloblastoma cells and undifferentiated granule neuron precursors in which Nur77 is upregulated and miR-124 is downregulated. Exogenous expression to further elevate Nur77 levels in Daoy cells increased proliferation and viability, but knocking down Nur77 via siRNA resulted in the opposite phenotype. Importantly, exogenous expression of miR-124 reduced Nur77 expression, cell viability, proliferation, and tumor spheroid size in 3D culture. In all, we have discovered miR-124 to be downregulated in instances of medulloblastoma in which Nur77 is upregulated, resulting in a proliferative state that abets cancer progression. This study provides evidence for increasing miR-124 expression as a potential therapy for cancers with elevated levels of Nur77. PMID- 26840409 TI - Projected Impact of Salt Restriction on Prevention of Cardiovascular Disease in China: A Modeling Study. AB - OBJECTIVES: To estimate the effects of achieving China's national goals for dietary salt (NaCl) reduction or implementing culturally-tailored dietary salt restriction strategies on cardiovascular disease (CVD) prevention. METHODS: The CVD Policy Model was used to project blood pressure lowering and subsequent downstream prevented CVD that could be achieved by population-wide salt restriction in China. Outcomes were annual CVD events prevented, relative reductions in rates of CVD incidence and mortality, quality-adjusted life-years (QALYs) gained, and CVD treatment costs saved. RESULTS: Reducing mean dietary salt intake to 9.0 g/day gradually over 10 years could prevent approximately 197 000 incident annual CVD events [95% uncertainty interval (UI): 173 000-219 000], reduce annual CVD mortality by approximately 2.5% (2.2-2.8%), gain 303 000 annual QALYs (278 000-329 000), and save approximately 1.4 billion international dollars (Int$) in annual CVD costs (Int$; 1.2-1.6 billion). Reducing mean salt intake to 6.0 g/day could approximately double these benefits. Implementing cooking salt restriction spoons could prevent 183 000 fewer incident CVD cases (153 000-215 000) and avoid Int$1.4 billion in CVD treatment costs annually (1.2-1.7 billion). Implementing a cooking salt substitute strategy could lead to approximately three times the health benefits of the salt-restriction spoon program. More than three quarters of benefits from any dietary salt reduction strategy would be realized in hypertensive adults. CONCLUSION: China could derive substantial health gains from implementation of population-wide dietary salt reduction policies. Most health benefits from any dietary salt reduction program would be realized in adults with hypertension. PMID- 26840410 TI - Clinical Implications of Cluster Analysis-Based Classification of Acute Decompensated Heart Failure and Correlation with Bedside Hemodynamic Profiles. AB - BACKGROUND: Classification of acute decompensated heart failure (ADHF) is based on subjective criteria that crudely capture disease heterogeneity. Improved phenotyping of the syndrome may help improve therapeutic strategies. OBJECTIVE: To derive cluster analysis-based groupings for patients hospitalized with ADHF, and compare their prognostic performance to hemodynamic classifications derived at the bedside. METHODS: We performed a cluster analysis on baseline clinical variables and PAC measurements of 172 ADHF patients from the ESCAPE trial. Employing regression techniques, we examined associations between clusters and clinically determined hemodynamic profiles (warm/cold/wet/dry). We assessed association with clinical outcomes using Cox proportional hazards models. Likelihood ratio tests were used to compare the prognostic value of cluster data to that of hemodynamic data. RESULTS: We identified four advanced HF clusters: 1) male Caucasians with ischemic cardiomyopathy, multiple comorbidities, lowest B type natriuretic peptide (BNP) levels; 2) females with non-ischemic cardiomyopathy, few comorbidities, most favorable hemodynamics; 3) young African American males with non-ischemic cardiomyopathy, most adverse hemodynamics, advanced disease; and 4) older Caucasians with ischemic cardiomyopathy, concomitant renal insufficiency, highest BNP levels. There was no association between clusters and bedside-derived hemodynamic profiles (p = 0.70). For all adverse clinical outcomes, Cluster 4 had the highest risk, and Cluster 2, the lowest. Compared to Cluster 4, Clusters 1-3 had 45-70% lower risk of all-cause mortality. Clusters were significantly associated with clinical outcomes, whereas hemodynamic profiles were not. CONCLUSIONS: By clustering patients with similar objective variables, we identified four clinically relevant phenotypes of ADHF patients, with no discernable relationship to hemodynamic profiles, but distinct associations with adverse outcomes. Our analysis suggests that ADHF classification using simultaneous considerations of etiology, comorbid conditions, and biomarker levels, may be superior to bedside classifications. PMID- 26840412 TI - Circulating Level of Neutrophil Extracellular Traps Is Not a Useful Biomarker for Assessing Disease Activity in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. AB - Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a group of life-threatening disorders, and frequently affects the kidneys. This study investigated whether the circulating neutrophil extracellular traps (NETs) levels were associated with disease activity of AAV. We collected serum samples from 34 patients with AAV in active stage and 62 patients with AAV in remission. Cell free DNA in serum was quantified using the Quant-iT PicoGreen assay. NETs associated MPO-DNA complexes, citrullinated-histone H3-DNA (cit-H3-DNA) complexes and the concentration of deoxyribonuclease I (DNase I) were quantified using ELISA. The activity of DNase I was quantified using radial enzyme-diffusion method. Associations between circulating levels of NETs with clinico-pathological parameters were analyzed. Serum levels of NETs in active AAV patients were significantly higher than those in healthy controls, and the level of cell free DNA correlated with C-reactive protein (CRP). However, no correlation was found between MPO-DNA complexes or cit-H3-DNA complexes level and CRP. Also there was no significant correlation between NETs level and initial serum creatinine, estimated glomerular filtration rate (eGFR), crescents formation or Birmingham Vasculitis Activity Score (BVAS). Furthermore, there was no significant difference of serum levels of cell free DNA or MPO-DNA complexes between active stage and remission of AAV. In conclusion, circulating levels of NETs cannot be used as a biomarker to assess disease activity in AAV patients. PMID- 26840413 TI - Identification of Copy Number Variations in Xiang and Kele Pigs. AB - Xiang and Kele pigs are two well-known local Chinese pig breeds that possess rich genetic resources and have enormous economic and scientific value. We performed a comprehensive genomic analysis of the copy number variations (CNVs) in these breeds. CNVs are one of the most important forms of genomic variation and have profound effects on phenotypic variation. In this study, PorcineSNP60 genotyping data from 98 Xiang pigs and 22 Kele pigs were used to identify CNVs. In total, 172 candidate CNV regions (CNVRs) were identified, ranging from 3.19 kb to 8175.26 kb and covering 80.41 Mb of the pig genome. Approximately 56.40% (97/172) of the CNVRs overlapped with those identified in seven previous studies, and 43.60% (75/172) of the identified CNVRs were novel. Of the identified CNVRs, 82 (47 gain, 33 loss, and two gain-loss events that covered 4.58 Mb of the pig genome) were found only in a Xiang population with a large litter size. In contrast, 13 CNVRs (8 gain and 5 loss events) were unique to a Xiang population with small litter sizes, and 30 CNVRs (14 loss and 16 gain events) were unique to Kele pigs. The CNVRs span approximately 660 annotated Sus scrofa genes that are significantly enriched for specific biological functions, such as sensory perception, cognition, reproduction, ATP biosynthetic processes, and neurological processes. Many CNVR-associated genes, particularly the genes involved in reproductive traits, differed between the Xiang populations with large and small litter sizes, and these genes warrant further investigation due to their importance in determining the reproductive performance of Xiang pigs. Our results provide meaningful information about genomic variation, which may be useful in future assessments of the associations between CNVs and important phenotypes in Xiang and Kele pigs to ultimately help protect these rare breeds. PMID- 26840417 TI - Where Is the Unbiased Information? PMID- 26840418 TI - Herbal Medicine for Cough: a Systematic Review and Meta-Analysis. AB - BACKGROUND: The aim of this review was to systematically assess the literature on herbal medicine for cough as a symptom of upper respiratory tract infections and common cold. METHODS: The Cochrane Library, Scopus, MEDLINE/PubMed, and Embase were searched through March 2012 for RCTs testing the effects of herbal medicine for cough. Risk of bias was assessed using the Cochrane tool. RESULTS: 34 RCTs (N = 7,083) on Pelargonium sidoides (11 RCTs), Echinacea (8 RCTs), Andrographis paniculata (6 RCTs), ivy/primrose/thyme (4 RCTs), essential oils (4 RCTs) and bakumondoto (1 RCT) were included. Controls were mainly placebo. Most studies had a low risk of bias. The meta-analysis revealed strong evidence for A. paniculata (SMD = -1.00, 95% CI = -1.85, -0.15; P<0.001) and ivy/primrose/thyme (RR = 1.40, 95% CI = 1.23, 1.60; P<0.001) in treating cough; moderate evidence for P. sidiodes (RR = 4.60; 95% CI = 2.89,7.31; P<0.001), and limited evidence for Echinacea (SMD = -0.68; 95% CI = -1.32, -0.04; P = 0.04). CONCLUSION: This review found strong evidence for A. paniculata and ivy/primrose/thyme-based preparations and moderate evidence for P. sidoides being significantly superior to placebo in alleviating the frequency and severity of patients' cough symptoms. Additional research, including other herbal treatments, is needed in this area. PMID- 26840414 TI - Risk Factors for Loss to Follow-Up among People Who Inject Drugs in a Risk Reduction Program at Karachi, Pakistan. A Case-Cohort Study. AB - INTRODUCTION: Retention of male people who inject drugs (PWIDs) is a major challenge for harm reduction programs that include sterile needle/syringe exchange in resource-limited settings like Pakistan. We assessed the risk factors for loss to follow-up among male PWIDs enrolled in a risk reduction program in Karachi, Pakistan. METHODS: We conducted a prospective cohort study among 636 HIV uninfected male PWIDs enrolled during March-June 2009 in a harm reduction program for the estimation of incidence rate. At 24 months post-enrollment, clients who had dropped out of the program were defined as lost to follow-up and included as cases for case-cohort study. RESULTS: The median age of the participants was 29 years (interquartile range: 23-36). Active outreach accounted for 76% (483/636) of cohort recruits. Loss to follow-up at 24 months was 25.5% (162/636). In multivariable logistic regression, younger age (AOR: 0.97, 95% CI: 0.92-0.99, p = 0.028), clients from other provinces than Sindh (AOR: 1.49, 95% CI: 1.01-2.22, p = 0.046), having no formal education (AOR: 3.44, 95% CI: 2.35-4.90, p<0.001), a history of incarceration (AOR: 1.68, 95% CI: 1.14-2.46, p<0.008), and being homeless (AOR: 1.47, 95% CI: 1.00-2.19, p<0.049) were associated with loss to follow-up. CONCLUSIONS: Our cohort retained 74.5% of male PWIDs in Karachi for 24 months. Its loss to follow up rate suggested substantial ongoing programmatic challenges. Programmatic enhancements are needed for the highest risk male PWIDs, i.e., younger men, men not from Sindh Province, men who are poorly educated, formerly incarcerated, and/or homeless. PMID- 26840415 TI - The Effect of Codon Mismatch on the Protein Translation System. AB - Incorrect protein translation, caused by codon mismatch, is an important problem of living cells. In this work, a computational model was introduced to quantify the effects of codon mismatch and the model was used to study the protein translation of Saccharomyces cerevisiae. According to simulation results, the probability of codon mismatch will increase when the supply of amino acids is unbalanced, and the longer is the codon sequence, the larger is the probability for incorrect translation to occur, making the synthesis of long peptide chain difficult. By comparing to simulation results without codon mismatch effects taken into account, the fraction of mRNAs with bound ribosome decrease faster along the mRNAs, making the 5' ramp phenomenon more obvious. It was also found in our work that the premature mechanism resulted from codon mismatch can reduce the proportion of incorrect translation when the amino acid supply is extremely unbalanced, which is one possible source of high fidelity protein synthesis after peptidyl transfer. PMID- 26840419 TI - [Potential Use of Healthcare Professions by Privately Insured Considering Complementary Medical Benefits]. AB - BACKGOUND: Patient preferences are becoming more and more important in healthcare and research. The aim of this study was to gain information about potential consultation of health professionals among a population of clients of a private insurer, considering complementary health care services of the insurer. METHODS: Based on 7 hypothetical afflictions (pain in chest, allergy, digestive complaints, depressive mood, knee swelling, reducing addictive substance, child with febrile infect) the surveyed were asked to indicate who they would turn to in the first and second place. The options were: a general practitioner, a conventionally-oriented specialist, a complementary-oriented specialist, an alternative practitioner, a pharmacist, and others. RESULTS: 1,960 insurants (74.1% male; 62.4 +/- 10.2 years) completed the questionnaire. In all potential afflictions the surveyed would prefer to consult a general practitioner in the first place, followed by a specialist. Only in case of allergy (12.5%) and depression (11.8%) or reduction of addictive substances (18.6%) they would also consider a complementary-oriented specialist as first choice. In case of depressive mood, allergy, digestive complaints, and angina pectoris the compliance was high, with Kappa >0.5. Moreover, a sensitivity analysis regarding gender and education showed a markedly higher compliance when the population was homogenized. DISCUSSION: Irrespective of the affliction, for the majority of the surveyed the general practitioner and specialist seem to be the first choice when it comes to health problems. Complementary-oriented specialists seem to be relevant only in specific disorders. PMID- 26840416 TI - Myocardial Structural and Biological Anomalies Induced by High Fat Diet in Psammomys obesus Gerbils. AB - BACKGROUND: Psammomys obesus gerbils are particularly prone to develop diabetes and obesity after brief period of abundant food intake. A hypercaloric high fat diet has been shown to affect cardiac function. Here, we sought to determine whether a short period of high fat feeding might alter myocardial structure and expression of calcium handling proteins in this particular strain of gerbils. METHODS: Twenty Psammomys obesus gerbils were randomly assigned to receive a normal plant diet (controls) or a high fat diet. At baseline and 16-week later, body weight, plasma biochemical parameters (including lipid and carbohydrate levels) were evaluated. Myocardial samples were collected for pathobiological evaluation. RESULTS: Sixteen-week high fat dieting resulted in body weight gain and hyperlipidemia, while levels of carbohydrates remained unchanged. At myocardial level, high fat diet induced structural disorganization, including cardiomyocyte hypertrophy, lipid accumulation, interstitial and perivascular fibrosis and increased number of infiltrating neutrophils. Myocardial expressions of pro-apoptotic Bax-to-Bcl-2 ratio, pro-inflammatory cytokines [interleukin (IL) 1beta and tumor necrosis factor (TNF)-alpha], intercellular (ICAM1) and vascular adhesion molecules (VCAM1) increased, while gene encoding cardiac muscle protein, the alpha myosin heavy polypeptide (MYH6), was downregulated. Myocardial expressions of sarco(endo)plasmic calcium-ATPase (SERCA2) and voltage-dependent calcium channel (Cacna1c) decreased, while protein kinase A (PKA) and calcium calmodulin-dependent protein kinase (CaMK2D) expressions increased. Myocardial expressions of ryanodine receptor, phospholamban and sodium/calcium exchanger (Slc8a1) did not change. CONCLUSIONS: We conclude that a relative short period of high fat diet in Psammomys obesus results in severe alterations of cardiac structure, activation of inflammatory and apoptotic processes, and altered expression of calcium-cycling determinants. PMID- 26840411 TI - Contributions of a Child's Built, Natural, and Social Environments to Their General Cognitive Ability: A Systematic Scoping Review. AB - The etiology of a child's cognitive ability is complex, with research suggesting that it is not attributed to a single determinant or even a defined period of exposure. Rather, cognitive development is the product of cumulative interactions with the environment, both negative and positive, over the life course. The aim of this systematic scoping review was to collate evidence associated with children's cognitive health, including inherent factors as well as chemical and non-chemical stressors from the built, natural, and social environments. Three databases were used to identify recent epidemiological studies (2003-2013) that examined exposure factors associated with general cognitive ability in children. Over 100 factors were evaluated from 258 eligible studies. We found that recent literature mainly assessed the hypothesized negative effects of either inherent factors or chemical exposures present in the physical environment. Prenatal growth, sleep health, lead and water pollutants showed consistent negative effects. Of the few studies that examined social stressors, results consistently showed cognitive development to be influenced by both positive and negative social interactions at home, in school or the community. Among behavioral factors related to diet and lifestyle choices of the mother, breastfeeding was the most studied, showing consistent positive associations with cognitive ability. There were mostly inconsistent results for both chemical and non-chemical stressors. The majority of studies utilized traditional exposure assessments, evaluating chemical and non-chemical stressors separately. Collective evidence from a limited number of studies revealed that cumulative exposure assessment that incorporates multiple chemical and non-chemical stressors over the life course may unravel the variability in effect on cognitive development and help explain the inconsistencies across studies. Future research examining the interactions of multiple stressors within a child's total environment, depicting a more real world exposure, will aid in understanding the cumulative effects associated with a child's ability to learn. PMID- 26840420 TI - Placebo by Proxy--the Influence of Parental Anxiety and Expectancy on Postoperative Morbidities in Children. AB - BACKGROUND: Placebo effects emerging from expectancies of relatives, also known as placebo by proxy, is a rather unexplored field. In this study, we assume a correlation between parental anxiety/expectancy and postoperative morbidities in children. Accordingly, a reduction of parental anxiety is expected to enhance the effect of treatment. METHODS: From October 2012 to June 2013, parents of 282 children completed a self-report closed-ended questionnaire embedded in a main RCT at three ambulatory care centers. RESULTS: There were no significant associations between parental expectancy or anxiety and children experiencing vomiting and pain. CONCLUSION: The present study is the first to investigate placebo by proxy in acupuncture treatment for children. The findings were not able to demonstrate any placebo effect by proxy. Unknown confounders and limitations of methods may have contributed to the negative findings. Thus, the findings must be read with precaution, as the possibility of a type II error cannot be excluded. TRIAL REGISTRATION: ClinicalTrials.gov NCT01729052. PMID- 26840421 TI - [Influence of Therapeutic Qi on Heart Rate Variability in Acupuncture: a Randomized Controlled Study]. AB - BACKGROUND: In a recent acupuncture study, volunteers were able to sense stimulation by 'therapeutic Qi' even when mechanical and psychological causes were excluded. Here, we investigated if 'therapeutic Qi' also influences the heart rate variability. METHODS: This was a controlled, randomized, single-blind crossover study with 30 volunteers. Using a special device, an acupuncture needle was inserted in the acupuncture point Pe6. With another device, the protruding end of the needle was fixed so that no transmission of mechanical movement to the tip was possible when the handle was touched. During the experimental intervention, the therapist touched the handle of the needle to stimulate Qi. During the control intervention, the needle was left untouched. During the null intervention, no needle was inserted. Before and after the interventions, parameters of heart rate variability (HRV) were measured. RESULTS: Between the 3 interventions no significant differences in HRV parameters were observed. From pre- to post-measurement the heart rate decreased in the control and experimental interventions (-2 min(-1), d = 0.24 and -2 min(-1), d = 0.24, respectively), RMSSD increased significantly when the needle was touched and Qi was stimulated (+9.7 ms, d = -0.32). CONCLUSION: Within this setting the subjectively perceived stimulation with therapeutic Qi could not be confirmed by using objective HRV measures. PMID- 26840423 TI - PC6 Acupressure Effectiveness in Patients with Postoperative Nausea and Vomiting after Craniotomy. PMID- 26840422 TI - [Acupuncture Therapy versus Disease-modifying Antirheumatic Drugs for the Treatment of Ankylosing Spondylitis--a Meta-analysis]. AB - BACKGROUND: We conducted a meta-analysis evaluating the efficacy and safety of acupuncture compared to disease-modifying antirheumatic drugs in patients with ankylosing spondylitis. METHODS: Four databases including Pubmed, EMBASE, Cochrane library, and ISI Web of Science were searched in December 2014, taking also the reference section into account. Randomized controlled trials that aimed to assess the efficacy of acupuncture therapy were identified. The inclusion criteria for the outcome measurements were the clinical effect, ESR, occipital wall test, chest expansion, CRP and finger ground distance. Finally, six studies met these inclusion criteria. Two reviewers screened each article independently and were blinded to the findings of each other. RESULTS: We analyzed data from 6 RCTs involving 541 participants. Acupuncture therapy could further improve the clinical effect (OR = 3.01; 95% CI, 1.48-6.13; P = 0.002) and reduce ESR level (SMD = -0.77; 95% CI, -1.46 to -0.08; P = 0.03) compared to DMARDs; a combination of acupuncture and DMARDs could further improve clinical effect (OR = 3.20, 95% CI, 1.36-7.54; P = 0.008), occipital-wall distance (SMD = -0.84; 95% CI, -1.37 to -0.31; P = 0.002), chest expansion (SMD = 0.38; 95% CI, 0.16-0.60; P = 0.0009), and finger-ground distance (SMD = -0.48; 95% CI, -0.87 to -0.09; P = 0.02) as compared to DMARDs treatment alone. CONCLUSIONS: Our findings support that acupuncture therapy could be an option to relieve symptoms associated with AS. These results should be interpreted cautiously due to the generally poor methodological qualities of the included trials. PMID- 26840424 TI - Controlling the Excited-State Dynamics of Nuclear Spin Isomers Using the Dynamic Stark Effect. AB - Stark control of chemical reactions uses intense laser pulses to distort the potential energy surfaces of a molecule, thus opening new chemical pathways. We use the concept of Stark shifts to convert a local minimum into a local maximum of the potential energy surface, triggering constructive and destructive wave packet interferences, which then induce different dynamics on nuclear spin isomers in the electronically excited state of a quinodimethane derivative. Model quantum-dynamical simulations on reduced dimensionality using optimized ultrashort laser pulses demonstrate a difference of the excited-state dynamics of two sets of nuclear spin isomers, which ultimately can be used to discriminate between these isomers. PMID- 26840425 TI - Use of De Novo Transcriptome Libraries to Characterize a Novel Oleaginous Marine Chlorella Species during the Accumulation of Triacylglycerols. AB - Marine chlorophytes of the genus Chlorella are unicellular algae capable of accumulating a high proportion of cellular lipids that can be used for biodiesel production. In this study, we examined the broad physiological capabilities of a subtropical strain (C596) of Chlorella sp. "SAG-211-18" including its heterotrophic growth and tolerance to low salt. We found that the alga replicates more slowly at diluted salt concentrations and can grow on a wide range of carbon substrates in the dark. We then sequenced the RNA of Chlorella strain C596 to elucidate key metabolic genes and investigate the transcriptomic response of the organism when transitioning from a nutrient-replete to a nutrient-deficient condition when neutral lipids accumulate. Specific transcripts encoding for enzymes involved in both starch and lipid biosynthesis, among others, were up regulated as the cultures transitioned into a lipid-accumulating state whereas photosynthesis-related genes were down-regulated. Transcripts encoding for two of the up-regulated enzymes-a galactoglycerolipid lipase and a diacylglyceride acyltransferase-were also monitored by reverse transcription quantitative polymerase chain reaction assays. The results of these assays confirmed the transcriptome-sequencing data. The present transcriptomic study will assist in the greater understanding, more effective application, and efficient design of Chlorella-based biofuel production systems. PMID- 26840426 TI - Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice. AB - AIM: To analyze the changes of different Lactobacillus species in ulcerative colitis patients and to further assess the therapeutic effects of selected Lactobacillus strains on dextran sulfate sodium (DSS)-induced experimental colitis in BALB/c mice. METHODS: Forty-five active ulcerative colitis (UC) patients and 45 population-based healthy controls were enrolled. Polymerase chain reaction (PCR) amplification and real-time PCR were performed for qualitative and quantitative analyses, respectively, of the Lactobacillus species in UC patients. Three Lactobacillus strains from three species were selected to assess the therapeutic effects on experimental colitis. Sixty 8-week-old BALB/c mice were divided into six groups. The five groups that had received DSS were administered normal saline, mesalazine, L. fermentum CCTCC M206110 strain, L. crispatus CCTCC M206119 strain, or L. plantarum NCIMB8826 strain. We assessed the severity of colitis based on disease activity index (DAI), body weight loss, colon length, and histologic damage. RESULTS: The detection rate of four of the 11 Lactobacillus species decreased significantly (P < 0.05), and the detection rate of two of the 11 Lactobacillus species increased significantly (P < 0.05) in UC patients. Relative quantitative analysis revealed that eight Lactobacillus species declined significantly in UC patients (P < 0.05), while three Lactobacillus species increased significantly (P < 0.05). The CCTCC M206110 treatment group had less weight loss and colon length shortening, lower DAI scores, and lower histologic scores (P < 0.05), while the CCTCC M206119 treatment group had greater weight loss and colon length shortening, higher histologic scores, and more severe inflammatory infiltration (P < 0.05). NCIMB8826 improved weight loss and colon length shortening (P < 0.05) with no significant influence on DAI and histologic damage in the colitis model. CONCLUSIONS: Administration of an L. crispatus CCTCC M206119 supplement aggravated DSS-induced colitis. L. fermentum CCTCC M206110 proved to be effective at attenuating DSS-induced colitis. The potential probiotic effect of L. plantarum NCIMB8826 on UC has yet to be assessed. PMID- 26840428 TI - Revisiting a classic case of introgression: hybridization and gene flow in Californian sunflowers. AB - During invasion, colonizing species can hybridize with native species, potentially swamping out native genomes. However, theory predicts that introgression will often be biased into the invading species. Thus, empirical estimates of gene flow between native and invasive species are important to quantify the actual threat of hybridization with invasive species. One classic example of introgression occurs in California, where Helianthus bolanderi was thought to be a hybrid between the serpentine endemic Helianthus exilis and the congeneric invader Helianthus annuus. We used genotyping by sequencing to look for signals of introgression and population structure. We find that H. bolanderi and H. exilis form one genetic clade, with weak population structure that is associated with geographic location rather than soil composition and likely represent a single species, not two. Additionally, while our results confirmed early molecular analysis and failed to support the hybrid origin of H. bolanderi, we did find evidence for introgression mainly into the invader H. annuus, as predicted by theory. PMID- 26840427 TI - A MORN1-associated HAD phosphatase in the basal complex is essential for Toxoplasma gondii daughter budding. AB - Apicomplexan parasites replicate by several budding mechanisms with two well characterized examples being Toxoplasma endodyogeny and Plasmodium schizogony. Completion of budding requires the tapering of the nascent daughter buds toward the basal end, driven by contraction of the basal complex. This contraction is not executed by any of the known cell division associated contractile mechanisms and in order to reveal new components of the unusual basal complex we performed a yeast two-hybrid screen with its major scaffolding protein, TgMORN1. Here we report on a conserved protein with a haloacid dehalogenase (HAD) phosphatase domain, hereafter named HAD2a, identified by yeast two-hybrid. HAD2a has demonstrated enzyme-activity in vitro, localizes to the nascent daughter buds, and co-localizes with MORN1 to the basal complex during its contraction. Conditional knockout of HAD2a in Toxoplasma interferes with basal complex assembly, which leads to incomplete cytokinesis and conjoined daughters that ultimately results in disrupted proliferation. In Plasmodium, we further confirmed localization of the HAD2a ortholog to the basal complex toward the end of schizogony. In conclusion, our work highlights an essential role for this HAD phosphatase across apicomplexan budding and suggests a regulatory mechanism of differential phosphorylation on the structure and/or contractile function of the basal complex. PMID- 26840429 TI - Comparative Quality Indicators for Hospital Choice: Do General Practitioners Care? AB - CONTEXT: The strategy of publicly reporting quality indicators is being widely promoted through public policies as a way to make health care delivery more efficient. OBJECTIVE: To assess general practitioners' (GPs) use of the comparative hospital quality indicators made available by public services and the media, as well as GPs' perceptions of their qualities and usefulness. METHOD: A telephone survey of a random sample representing all self-employed GPs in private practice in France. RESULTS: A large majority (84.1%-88.5%) of respondents (n = 503; response rate of 56%) reported that they never used public comparative indicators, available in the mass media or on government and non-government Internet sites, to influence their patients' hospital choices. The vast majority of GPs rely mostly on traditional sources of information when choosing a hospital. At the same time, this study highlights favourable opinions shared by a large proportion of GPs regarding several aspects of hospital quality indicators, such as their good qualities and usefulness for other purposes. In sum, the results show that GPs make very limited use of hospital quality indicators based on a consumer choice paradigm but, at the same time, see them as useful in ways corresponding more to the usual professional paradigms, including as a means to improve quality of care. PMID- 26840430 TI - Complete Mitochondrial Genome of Three Bactrocera Fruit Flies of Subgenus Bactrocera (Diptera: Tephritidae) and Their Phylogenetic Implications. AB - Bactrocera latifrons is a serious pest of solanaceous fruits and Bactrocera umbrosa is a pest of Artocarpus fruits, while Bactrocera melastomatos infests the fruit of Melastomataceae. They are members of the subgenus Bactrocera. We report here the complete mitochondrial genome of these fruit flies determined by next generation sequencing and their phylogeny with other taxa of the subgenus Bactrocera. The whole mitogenomes of these three species possessed 37 genes namely, 13 protein-coding genes (PCGs), 2 rRNA and 22 tRNA genes. The mitogenome of B. latifrons (15,977 bp) was longer than those of B. melastomatos (15,954 bp) and B. umbrosa (15,898 bp). This difference can be attributed to the size of the intergenic spacers (283 bp in B. latifrons, 261 bp in B. melastomatos, and 211 bp in B. umbrosa). Most of the PCGs in the three species have an identical start codon, except for atp8 (adenosine triphosphate synthase protein 8), which had an ATG instead of GTG in B. umbrosa, whilst the nad3 (NADH dehydrogenase subunit 3) and nad6 (NADH dehydrogenase subunit 6) genes were characterized by an ATC instead of ATT in B. melastomatos. The three species had identical stop codon for the respective PCGs. In B. latifrons and B. melastomatos, the TPsiC (thymidine pseudouridine-cytidine)-loop was absent in trnF (phenylalanine) and DHU (dihydrouracil)-loop was absent in trnS1 (serine S1). In B. umbrosa, trnN (asparagine), trnC (cysteine) and trnF lacked the TpsiC-loop, while trnS1 lacked the DHU-stem. Molecular phylogeny based on 13 PCGs was in general concordant with 15 mitochondrial genes (13 PCGs and 2 rRNA genes), with B. latifrons and B. umbrosa forming a sister group basal to the other species of the subgenus Bactrocera which was monophyletic. The whole mitogenomes will serve as a useful dataset for studying the genetics, systematics and phylogenetic relationships of the many species of Bactrocera genus in particular, and tephritid fruit flies in general. PMID- 26840433 TI - Computer Modeling of Halogen Bonds and Other sigma-Hole Interactions. AB - In the field of noncovalent interactions a new paradigm has recently become popular. It stems from the analysis of molecular electrostatic potentials and introduces a label, which has recently attracted enormous attention. The label is sigma-hole, and it was first used in connection with halogens. It initiated a renaissance of interest in halogenated compounds, and later on, when found also on other groups of atoms (chalcogens, pnicogens, tetrels and aerogens), it resulted in a new direction of research of intermolecular interactions. In this review, we summarize advances from about the last 10 years in understanding those interactions related to sigma-hole. We pay particular attention to theoretical and computational techniques, which play a crucial role in the field. PMID- 26840432 TI - Women Are Seen More than Heard in Online Newspapers. AB - Feminist news media researchers have long contended that masculine news values shape journalists' quotidian decisions about what is newsworthy. As a result, it is argued, topics and issues traditionally regarded as primarily of interest and relevance to women are routinely marginalised in the news, while men's views and voices are given privileged space. When women do show up in the news, it is often as "eye candy," thus reinforcing women's value as sources of visual pleasure rather than residing in the content of their views. To date, evidence to support such claims has tended to be based on small-scale, manual analyses of news content. In this article, we report on findings from our large-scale, data-driven study of gender representation in online English language news media. We analysed both words and images so as to give a broader picture of how gender is represented in online news. The corpus of news content examined consists of 2,353,652 articles collected over a period of six months from more than 950 different news outlets. From this initial dataset, we extracted 2,171,239 references to named persons and 1,376,824 images resolving the gender of names and faces using automated computational methods. We found that males were represented more often than females in both images and text, but in proportions that changed across topics, news outlets and mode. Moreover, the proportion of females was consistently higher in images than in text, for virtually all topics and news outlets; women were more likely to be represented visually than they were mentioned as a news actor or source. Our large-scale, data-driven analysis offers important empirical evidence of macroscopic patterns in news content concerning the way men and women are represented. PMID- 26840431 TI - Rapid Expansion of Human Epithelial Stem Cells Suitable for Airway Tissue Engineering. AB - RATIONALE: Stem cell-based tracheal replacement represents an emerging therapeutic option for patients with otherwise untreatable airway diseases including long-segment congenital tracheal stenosis and upper airway tumors. Clinical experience demonstrates that restoration of mucociliary clearance in the lungs after transplantation of tissue-engineered grafts is critical, with preclinical studies showing that seeding scaffolds with autologous mucosa improves regeneration. High epithelial cell-seeding densities are required in regenerative medicine, and existing techniques are inadequate to achieve coverage of clinically suitable grafts. OBJECTIVES: To define a scalable cell culture system to deliver airway epithelium to clinical grafts. METHODS: Human respiratory epithelial cells derived from endobronchial biopsies were cultured using a combination of mitotically inactivated fibroblasts and Rho-associated protein kinase (ROCK) inhibition using Y-27632 (3T3+Y). Cells were analyzed by immunofluorescence, quantitative polymerase chain reaction, and flow cytometry to assess airway stem cell marker expression. Karyotyping and multiplex ligation dependent probe amplification were performed to assess cell safety. Differentiation capacity was tested in three-dimensional tracheospheres, organotypic cultures, air-liquid interface cultures, and an in vivo tracheal xenograft model. Ciliary function was assessed in air-liquid interface cultures. MEASUREMENTS AND MAIN RESULTS: 3T3-J2 feeder cells and ROCK inhibition allowed rapid expansion of airway basal cells. These cells were capable of multipotent differentiation in vitro, generating both ciliated and goblet cell lineages. Cilia were functional with normal beat frequency and pattern. Cultured cells repopulated tracheal scaffolds in a heterotopic transplantation xenograft model. CONCLUSIONS: Our method generates large numbers of functional airway basal epithelial cells with the efficiency demanded by clinical transplantation, suggesting its suitability for use in tracheal reconstruction. PMID- 26840434 TI - siRNA and RNAi optimization. AB - The discovery and examination of the posttranscriptional gene regulatory mechanism known as RNA interference (RNAi) contributed to the identification of small interfering RNA (siRNA) and the comprehension of its enormous potential for clinical purposes. Theoretically, the ability of specific target gene downregulation makes the RNAi pathway an appealing solution for several diseases. Despite numerous hurdles resulting from the inherent properties of siRNA molecule and proper delivery to the target tissue, more than 50 RNA-based drugs are currently under clinical testing. In this work, we analyze the recent literature in the optimization of siRNA molecules. In detail, we focused on describing the most recent advances of siRNA field aimed at optimize siRNA pharmacokinetic properties. Special attention has been given in describing the impact of RNA modifications in the potential off-target effects (OTEs) such as saturation of the RNAi machinery, passenger strand-mediated silencing, immunostimulation, and miRNA-like OTEs as well as to recent developments on the delivery issue. The novel delivery systems and modified siRNA provide significant steps toward the development of reliable siRNA molecules for therapeutic use. WIREs RNA 2016, 7:316-329. doi: 10.1002/wrna.1337 For further resources related to this article, please visit the WIREs website. PMID- 26840435 TI - Differential Regulation of Eicosanoid and Endocannabinoid Production by Inflammatory Mediators in Human Choriodecidua. AB - An increase in intrauterine prostaglandin production is critical for the onset and progression of labor in women and indeed all mammalian species studied. Endocannabinoids can act as substrates for enzymes of the prostaglandin biosynthetic pathways and can be utilized to generate other related compounds such as prostamides. The end products are indistinguishable by radioimmunoassay. We have separated such compounds by mass spectrometry. We now show that inflammatory stimuli such as LPS and proinflammatory cytokines act differentially on these pathways in human choriodecidua and preferentially create drive through to prostaglandin end products. These findings create doubt about the interpretation of data on prostaglandin biosynthesis in intrauterine tissues from pregnant women especially in the presence of an infection. The possibility is raised that separation of these products might reduce variability in results and lead to potential uses for their measurement in the diagnosis of preterm labor. PMID- 26840436 TI - Effect of Superimposed Electromyostimulation on Back Extensor Strengthening: A Pilot Study. AB - Park, JH, Seo, KS, and Lee, S-U. Effect of superimposed electromyostimulation on back extensor strengthening: a pilot study. J Strength Cond Res 30(9): 2470-2475, 2016-Electromyostimulation (EMS) superimposed on voluntary contraction (VC) can increase muscle strength. However, no study has examined the effect of superimposing EMS on back extensor strengthening. The purpose of this study was to determine the effect of superimposed EMS on back extensor strengthening in healthy adults. Twenty healthy men, 20-29 years of age, without low-back pain were recruited. In the EMS group, electrodes were attached to bilateral L2 and L4 paraspinal muscles. Stimulation intensity was set for maximally tolerable intensity. With VC, EMS was superimposed for 10 seconds followed by a 20-second rest period. The same protocol was used in the sham stimulation (SS) group, except that the stimulation intensity was set at the lowest intensity (5 mA). All subjects performed back extension exercise using a Swiss ball, with 10 repetitions per set, 2 sets each day, 5 times a week for 2 weeks. The primary outcome measure was the change in isokinetic strength of the back extensor using an isokinetic dynamometer. Additionally, endurance was measured using the Sorensen test. After 2 weeks of back extension exercise, the peak torque and endurance increased significantly in both groups (p <= 0.05). Effect size between the EMS group and the SS group was medium in strength and endurance. However, there was no statistically significant difference between 2 groups. In conclusion, 2 weeks of back extensor strengthening exercise was effective for strength and endurance. Superimposing EMS on back extensor strengthening exercise could provide an additional effect on increasing strength. PMID- 26840438 TI - Benefits of Compression Garments Worn During Handball-Specific Circuit on Short Term Fatigue in Professional Players. AB - Ravier, G, Bouzigon, R, Beliard, S, Tordi, N, and Grappe, F. Benefits of compression garments worn during handball-specific circuit on short-term fatigue in professional players. J Strength Cond Res 32(12): 3528-3536, 2018-The purpose of this study was to investigate the benefits of full-leg length compression garments (CGs) worn during a handball-specific circuit exercises on athletic performance and acute fatigue-induced changes in strength and muscle soreness in professional handball players. Eighteen men (mean +/- SD: age 23.22 +/- 4.97 years; body mass: 82.06 +/- 9.69 kg; height: 184.61 +/- 4.78 cm) completed 2 identical sessions either wearing regular gym short or CGs in a randomized crossover design. Exercise circuits of explosive activities included 3 periods of 12 minutes of sprints, jumps, and agility drills every 25 seconds. Before, immediately after and 24 hours postexercise, maximal voluntary knee extension (maximal voluntary contraction, MVC), rate of force development (RFD), and muscle soreness were assessed. During the handball-specific circuit sprint and jump performances were unchanged in both conditions. Immediately after performing the circuit exercises MVC, RFD, and PPT decreased significantly compared with preexercise with CGs and noncompression clothes. Decrement was similar in both conditions for RFD (effect size, ES = 0.40) and PPT for the soleus (ES = 0.86). However, wearing CGs attenuated decrement in MVC (p < 0.001) with a smaller decrease (ES = 1.53) in CGs compared with regular gym shorts condition (-5.4 vs. 18.7%, respectively). Full recovery was observed 24 hours postexercise in both conditions for muscle soreness, MVC, and RFD. These findings suggest that wearing CGs during a handball-specific circuit provides benefits on the impairment of the maximal muscle force characteristics and is likely to be worthwhile for handball players involved in activities such as tackles. PMID- 26840437 TI - Comparison of Two Fluid Replacement Protocols During a 20-km Trail Running Race in the Heat. AB - Lopez, RM, Casa, DJ, Jensen, K, Stearns, RL, DeMartini, JK, Pagnotta, KD, Roti, MW, Armstrong, LE, and Maresh, CM. Comparison of two fluid replacement protocols during a 20-km trail running race in the heat. J Strength Cond Res 30(9): 2609 2616, 2016-Proper hydration is imperative for athletes striving for peak performance and safety, however, the effectiveness of various fluid replacement strategies in the field setting is unknown. The purpose of this study was to investigate how two hydration protocols affect physiological responses and performance during a 20-km trail running race. A randomized, counter-balanced, crossover design was used in a field setting (mean +/- SD: WBGT 28.3 +/- 1.9 degrees C). Well-trained male (n = 8) and female (n = 5) runners (39 +/- 14 years; 175 +/- 9 cm; 67.5 +/- 11.1 kg; 13.4 +/- 4.6% BF) completed two 20-km trail races (5 * 4-km loop) with different water hydration protocols: (a) ad libitum (AL) consumption and (b) individualized rehydration (IR). Data were analyzed using repeated measures ANOVA. Paired t-tests compared pre-race-post race measures. Main outcome variables were race time, heart rate (HR), gastrointestinal temperature (TGI), fluid consumed, percent body mass loss (BML), and urine osmolality (Uosm). Race times between groups were similar. There was a significant condition * time interaction (p = 0.048) for HR, but TGI was similar between conditions. Subjects replaced 30 +/- 14% of their water losses in AL and 64 +/- 16% of their losses in IR (p < 0.001). Ad libitum trial experienced greater BML (-2.6 +/- 0.5%) compared with IR (-1.3 +/- 0.5%; p < 0.001). Pre-race to post-race Uosm differences existed between AL (-273 +/- 146 mOsm) and IR (-145 +/- 215 mOsm, p = 0.032). In IR, runners drank twice as much fluid than AL during the 20-km race, leading to > 2% BML in AL. Ad libitum drinking resulted in 1.3% greater BML over the 20-km race, which resulted in no thermoregulatory or performance differences from IR. PMID- 26840439 TI - Breast Cancer-Related Lymphedema and Resistance Exercise: A Systematic Review. AB - Nelson, NL. Breast cancer-related lymphedema and resistance exercise: a systematic review. J Strength Cond Res 30(9): 2656-2665, 2016-Breast cancer related lymphedema (BCRL) is characterized by the accumulation of fluid in the interstitial tissues in the arm, shoulder, neck, or torso and attributed to the damage of lymph nodes during breast cancer treatments involving radiation and axillary node dissection. Resistance exercise training (RET) has recently shown promise in the management of BCRL. The aims of this review were twofold: (a) To summarize the results of recent randomized controlled trials (RCTs) investigating the effect of resistance exercise in those with, or at risk for, BCRL. (b) To determine whether breast cancer survivors can perform RET at sufficient intensities to elicit gains in strength without causing BCRL flare-up or incidence. A search was performed on the electronic databases PubMed, MEDLINE, SPORT Discus, and Science Direct, up to July 10, 2015, using the following keywords: breast cancer-related lymphedema, strength training, resistance training, systematic review, and breast cancer. Manual searches of references were also conducted for additional relevant studies. A total of 6 RCTs, involving 805 breast cancer survivors, met the inclusion criteria and corresponded to the aims of this review. The methodological quality of included RCTs was good, with a mean score 6.8 on the 10-point PEDro scale. The results of this review indicate that breast cancer survivors can perform RET at high-enough intensities to elicit strength gains without triggering changes to lymphedema status. There is strong evidence indicating that RET produces significant gains in muscular strength without provoking BCRL. PMID- 26840440 TI - An Examination of Muscle Activation and Power Characteristics While Performing the Deadlift Exercise With Straight and Hexagonal Barbells. AB - The deadlift exercise is commonly performed to develop strength and power, and to train the lower-body and erector spinae muscle groups. However, little is known about the acute training effects of a hexagonal barbell vs. a straight barbell when performing deadlifts. Therefore, the purpose of this study was to examine the hexagonal barbell in comparison with the straight barbell by analyzing electromyography (EMG) from the vastus lateralis, biceps femoris, and erector spinae, as well as peak force, peak power, and peak velocity using a force plate. Twenty men with deadlifting experience volunteered to participate in the study. All participants completed a 1 repetition maximum (1RM) test with each barbell on 2 separate occasions. Three repetitions at 65 and 85% 1RM were performed with each barbell on a third visit. The results revealed that there was no significant difference for 1RM values between the straight and hexagonal barbells (mean +/- SD in kg = 181.4 +/- 27.3 vs. 181.1 +/- 27.6, respectively) (p > 0.05). Significantly greater normalized EMG values were found from the vastus lateralis for both the concentric (1.199 +/- 0.22) and eccentric (0.879 +/- 0.31) phases of the hexagonal-barbell deadlift than those of the straight-barbell deadlift (0.968 +/- 0.22 and 0.559 +/- 1.26), whereas the straight-barbell deadlift led to significantly greater EMG values from the bicep femoris during the concentric phase (0.835 +/- 0.19) and the erector spinae (0.753 +/- 0.28) during the eccentric phase than the corresponding values for the hexagonal-barbell deadlift (0.723 +/- 0.20 and 0.614 +/- 0.21) (p <= 0.05). In addition, the hexagonal barbell deadlift demonstrated significantly greater peak force (2,553.20 +/- 371.52 N), peak power (1,871.15 +/- 451.61 W), and peak velocity (0.805 +/- 0.165) values than those of the straight-barbell deadlift (2,509.90 +/- 364.95 N, 1,639.70 +/- 361.94 W, and 0.725 +/- 0.138 m.s, respectively) (p <= 0.05). These results suggest that the barbells led to different patterns of muscle activation and that the hexagonal barbell may be more effective at developing maximal force, power, and velocity. PMID- 26840441 TI - Electromyographic and Force Plate Analysis of the Deadlift Performed With and Without Chains. AB - The purpose of this study was to determine the effects of deadlift chain variable resistance on surface electromyography (EMG) of the gluteus maximus, erector spinae, and vastus lateralis muscles, ground reaction forces (GRFs), and rate of force development (RFD). Thirteen resistance-trained men (24.0 +/- 2.1 years, 179.3 +/- 4.8 cm, 87.0 +/- 10.6 kg) volunteered for the study. On day 1, subjects performed 1 repetition maximum (1RM) testing of the deadlift exercise. On day 2, subjects performed one set of 3 repetitions with a load of 85% 1RM with chains (CH) and without chains (NC). The order of the CH and NC conditions was randomly determined for each subject. For the CH condition, the chains accounted for approximately 20% (19.9 +/- 0.6%) of the 85% 1RM load, matched at the top of the lift. Surface EMG was recorded to differentiate muscle activity between conditions (CH, NC), range of motion (ROM; bottom, top), and phase (concentric, eccentric). Peak GRFs and RFD were measured using a force plate. Electromyography results revealed that for the gluteus maximus there was significantly greater EMG activity during the NC condition vs. the CH condition. For the erector spinae, EMG activity was greater at the bottom than the top ROM (p <= 0.05). Force plate results revealed that deadlifting at 85% 1RM with an accommodating chain resistance of approximately 20% results in a reduction in GRFs (p <= 0.05) and no change in RFD (p > 0.05). Collectively, these results suggest that the use of chain resistance during deadlifting can alter muscle activation and force characteristics of the lift. PMID- 26840442 TI - Consistency of Lower-Body Dimensions Using Surface Landmarks and Simple Measurement Tools. AB - Caia, J, Weiss, LW, Chiu, LZF, Schilling, BK, and Paquette, MR. Consistency of lower-body dimensions using surface landmarks and simple measurement tools. J Strength Cond Res 30(9): 2600-2608, 2016-Body dimensions may influence various types of physical performance. This study was designed to establish the reliability and precision of bilateral lower-body dimensions using surface anatomic landmarks and either sliding calipers or goniometry. Fifty university students (25 men and 25 women) were measured on 2 separate occasions separated by 48 or 72 hours. A small digital caliper was used to acquire longitudinal dimensions of the feet, whereas a larger broad-blade caliper was used to measure lower-limb, hip, and pelvic dimensions. Quadriceps angle (Q-angle) was determined through surface goniometry. Data for all foot and lower-limb dimensions were both reliable and precise (intraclass correlation coefficient (ICC) >=0.72, SEM 0.1 0.5 cm). Measures of Q-angle were also reliable and precise (ICC >=0.85, SEM 0.2 0.4 degrees ). Findings from this investigation demonstrate that lower-body dimensions may be reliably and precisely measured through simple practical tests, when surface anatomic landmarks and standardized procedures are used. Although intertester reliability remains to be established, meticulous adherence to specific measurement protocols is likely to yield viable output for lower-body dimensions when more sophisticated methods are unavailable or inappropriate. PMID- 26840443 TI - Genetic variability among power athletes: The stronger vs. the faster. AB - Athletic events can be divided into "aerobic-type event" or "anaerobic-type event" based on energetic usage. Power, speed, and strength, also used to specify sports subtypes. Weightlifters, sprinters, and jumpers feature high-intensity efforts lasting few seconds. However, their performance requires different proportions of power, speed, and strength. The aim of the current study was to examine genetic differences between subtypes of anaerobic athletes in 3 genetic variants: ACTN3 R577X, which is associated with muscle contractions, AGT Met235Thr which is associated with muscle growth, and PPARD T/C, which is associated with aerobic capacity. 71 sprinters and jumpers (S/J), 54 weightlifters (WL) and 86 controls participated in the study. Genomic DNA was extracted from peripheral blood using standard protocol. Genotypes were determined using Taqman allelic discrimination assay. ACTN3 RR-genotype frequency was significantly higher among S/J (39.4%) compared to WL (22.2%) and controls (18.6%). AGT ThrThr-genotype was significantly higher among WL (25.9%) compared to S/J (4.2%) and controls (12.8%). PPARD T294C genotype frequencies did not differ between groups. The results suggest that there may be a specific genetic makeup enabling an athlete to excel in speed-oriented events (sprints), rather than in strength-oriented events (weightlifting). PMID- 26840444 TI - A Comparison of Athletic Movement Among Talent-Identified Juniors From Different Football Codes in Australia: Implications for Talent Development. AB - Woods, CT, Keller, BS, McKeown, I, and Robertson, S. A comparison of athletic movement among talent-identified juniors from different football codes in Australia: implications for talent development. J Strength Cond Res 30(9): 2440 2445, 2016-This study aimed to compare the athletic movement skill of talent identified (TID) junior Australian Rules football (ARF) and soccer players. The athletic movement skill of 17 TID junior ARF players (17.5-18.3 years) was compared against 17 TID junior soccer players (17.9-18.7 years). Players in both groups were members of an elite junior talent development program within their respective football codes. All players performed an athletic movement assessment that included an overhead squat, double lunge, single-leg Romanian deadlift (both movements performed on right and left legs), a push-up, and a chin-up. Each movement was scored across 3 essential assessment criteria using a 3-point scale. The total score for each movement (maximum of 9) and the overall total score (maximum of 63) were used as the criterion variables for analysis. A multivariate analysis of variance tested the main effect of football code (2 levels) on the criterion variables, whereas a 1-way analysis of variance identified where differences occurred. A significant effect was noted, with the TID junior ARF players outscoring their soccer counterparts when performing the overhead squat and push-up. No other criterions significantly differed according to the main effect. Practitioners should be aware that specific sporting requirements may incur slight differences in athletic movement skill among TID juniors from different football codes. However, given the low athletic movement skill noted in both football codes, developmental coaches should address the underlying movement skill capabilities of juniors when prescribing physical training in both codes. PMID- 26840445 TI - Was Frozen Mammoth or Giant Ground Sloth Served for Dinner at The Explorers Club? AB - Accounts of woolly mammoths (Mammuthus primigenius) preserved so well in ice that their meat is still edible have a long history of intriguing the public and influencing paleontological thought on Quaternary extinctions and climate, with some scientists resorting to catastrophism to explain the instantaneous freezing necessary to preserve edible meat. Famously, members of The Explorers Club purportedly dined on frozen mammoth from Alaska, USA, in 1951. This event, well received by the press and general public, became an enduring legend for the Club and popularized the notorious annual tradition of serving rare and exotic food at Club dinners that continues to this day. The Yale Peabody Museum holds a sample of meat preserved from the 1951 meal, interestingly labeled as a South American giant ground sloth (Megatherium), not mammoth. We sequenced a fragment of the mitochondrial cytochrome-b gene and studied archival material to verify its identity, which if genuine, would extend the range of Megatherium over 600% and alter our views on ground sloth evolution. Our results indicate that the meat was not mammoth or Megatherium but green sea turtle (Chelonia mydas). The prehistoric dinner was likely an elaborate publicity stunt. Our study emphasizes the value of museums collecting and curating voucher specimens, particularly those used for evidence of extraordinary claims. PMID- 26840446 TI - Emerging strategies for the treatment of gastroparesis. AB - Gastroparesis is a syndrome of delayed gastric emptying in the absence of mechanical obstruction. Symptoms can be debilitating, affect nutritional states, and significantly impact patients' quality of life. The management of these patients can prove quite difficult to many providers. This article will review the current management recommendations of gastroparesis, discuss investigational medications and interventions, and summarize future directions of therapies targeting the underlying disease process. Current therapies are subdivided into those improving gastric motility and those directly targeting symptoms. Non pharmacologic interventions, including gastric stimulator implantation and intra pyloric botulinum toxic injection are reviewed. A discussion of expert opinion in the field, a look into the future of gastroparesis management, and a key point summary conclude the article. PMID- 26840447 TI - Inhibition of cell proliferation, migration and invasion by a glioma-targeted fusion protein combining the p53 C terminus and MDM2-binding domain. AB - OBJECTIVES: The aim of this study was to develop multifunctional fusion proteins for targeting and delivering therapy elements into glioma cells. MATERIALS AND METHODS: Multifunctional fusion proteins were expressed in Escherichia coli and purified using Ni-NTA resin affinity chromatography. Human glioma cells and primary astrocytes were used to analyse their functions. Targeting proteins location to glioma cells was observed by confocal microscopy. Effects of cell viability and proliferation were evaluated using the Cell Counting Kit 8 and colony formation assays. Glioma cell migration and invasion were assessed using transwell assays, and apoptosis was analysed by flow cytometry. In addition, changes in expression of proteins related to the cell cycle and apoptosis were determined by Western blotting. RESULTS: The protein with highest bioactivity was GL1-riHA2-p53c+m-TAT (GHPc+mT), which combines glioma-targeting peptide GL1 (G), and C terminus (Pc) and mouse double minute domains (Pm) of p53, with the destabilizing lipid membrane peptide riHA2 (H) and cell-penetrating peptide TAT (T). The purified fusion protein was stable in cell culture medium and specifically targeted, and was internalized by, epidermal growth factor receptor (EGFR)-overexpressing glioma cells (U87DeltaEGFR). It inhibited cell proliferation, migration and invasion, while flow cytometric analysis showed increased apoptosis. In addition, GHPc+mT caused significant changes in expression of proteins related to the cell cycle and apoptosis. CONCLUSION: GHPc+mT is a multifunctional protein combining targeting, inhibition of glioma cell proliferation and induction of apoptosis, providing some potential to be developed into an effective protein drug delivery system for glioma therapy. PMID- 26840449 TI - Genome-Wide Detection of SNP and SV Variations to Reveal Early Ripening-Related Genes in Grape. AB - Early ripening in grape (Vitis vinifera L.) is a crucial agronomic trait. The fruits of the grape line 'Summer Black' (SBBM), which contains a bud mutation, can be harvested approximately one week earlier than the 'Summer Black' (SBC)control. To investigate the molecular mechanism of the bud mutation related to early ripening, we detected genome-wide genetic variations based on re sequencing. In total, 3,692,777 single nucleotide polymorphisms (SNPs) and 81,223 structure variations (SVs) in the SBC genome and 3,823,464 SNPs and 85,801 SVs in the SBBM genome were detected compared with the reference grape sequence. Of these, 635 SBC-specific genes and 665 SBBM-specific genes were screened. Ripening and colour-associated unigenes with non-synonymous mutations (NS), SVs or frame shift mutations (F) were analysed. The results showed that 90 unigenes in SBC, 76 unigenes in SBBM and 13 genes that mapped to large fragment indels were filtered. The expression patterns of eight genes were confirmed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR).The re-sequencing data showed that 635 SBC-specific genes and 665 SBBM-specific genes associated with early ripening were screened. Among these, NCED6 expression appears to be related to NCED1 and is involved in ABA biosynthesis in grape, which might play a role in the onset of anthocyanin accumulation. The SEP and ERF genes probably play roles in ethylene response. PMID- 26840448 TI - Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue. AB - INTRODUCTION: Left ventricular dysfunction is a frequent and potentially severe side effect of many tyrosine kinase inhibitors (TKI). The mode of toxicity is not identified, but may include impairment of mitochondrial or sarcomeric function, autophagy or angiogenesis, either as an on-target or off-target mechanism. METHODS AND RESULTS: We studied concentration-response curves and time courses for nine TKIs in three-dimensional, force generating engineered heart tissue (EHT) from neonatal rat heart cells. We detected a concentration- and time dependent decline in contractile force for gefitinib, lapatinib, sunitinib, imatinib, sorafenib, vandetanib and lestaurtinib and no decline in contractile force for erlotinib and dasatinib after 96 hours of incubation. The decline in contractile force was associated with an impairment of autophagy (LC3 Western blot) and appearance of autophagolysosomes (transmission electron microscopy). CONCLUSION: This study demonstrates the feasibility to study TKI-mediated force effects in EHTs and identifies an association between a decline in contractility and inhibition of autophagic flux. PMID- 26840450 TI - Transcription Factors Oct-1 and GATA-3 Cooperatively Regulate Th2 Cytokine Gene Expression via the RHS5 within the Th2 Locus Control Region. AB - The T helper type 2 (Th2) locus control region (LCR) regulates Th2 cell differentiation. Several transcription factors bind to the LCR to modulate the expression of Th2 cytokine genes, but the molecular mechanisms behind Th2 cytokine gene regulation are incompletely understood. Here, we used database analysis and an oligonucleotide competition/electrophoretic mobility shift assays to search for transcription factors binding to RHS5, a DNase I hypersensitive site (DHS) within the Th2 LCR. Consequently, we demonstrated that GATA-binding protein-3 (GATA-3), E26 transformation-specific protein 1 (Ets-1), octamer transcription factor-1 (Oct-1), and Oct-2 selectively associate with RHS5. Furthermore, chromatin immunoprecipitation and luciferase reporter assays showed that Oct-1 and Oct-2 bound within the Il4 promoter region and the Th2 LCR, and that Oct-1 and GATA-3 or Oct-2 synergistically triggered the transactivational activity of the Il4 promoter through RHS5. These results suggest that Oct-1 and GATA-3/Oct-2 direct Th2 cytokine gene expression in a cooperative manner. PMID- 26840451 TI - DianaHealth.com, an On-Line Database Containing Appraisals of the Clinical Value and Appropriateness of Healthcare Interventions: Database Development and Retrospective Analysis. AB - OBJECTIVE: To describe the development of a novel on-line database aimed to serve as a source of information concerning healthcare interventions appraised for their clinical value and appropriateness by several initiatives worldwide, and to present a retrospective analysis of the appraisals already included in the database. METHODS AND FINDINGS: Database development and a retrospective analysis. The database DianaHealth.com is already on-line and it is regularly updated, independent, open access and available in English and Spanish. Initiatives are identified in medical news, in article references, and by contacting experts in the field. We include appraisals in the form of clinical recommendations, expert analyses, conclusions from systematic reviews, and original research that label any health care intervention as low-value or inappropriate. We obtain the information necessary to classify the appraisals according to type of intervention, specialties involved, publication year, authoring initiative, and key words. The database is accessible through a search engine which retrieves a list of appraisals and a link to the website where they were published. DianaHealth.com also provides a brief description of the initiatives and a section where users can report new appraisals or suggest new initiatives. From January 2014 to July 2015, the on-line database included 2940 appraisals from 22 initiatives: eleven campaigns gathering clinical recommendations from scientific societies, five sets of conclusions from literature review, three sets of recommendations from guidelines, two collections of articles on low clinical value in medical journals, and an initiative of our own. CONCLUSIONS: We have developed an open access on-line database of appraisals about healthcare interventions considered of low clinical value or inappropriate. DianaHealth.com could help physicians and other stakeholders make better decisions concerning patient care and healthcare systems sustainability. Future efforts should be focused on assessing the impact of these appraisals in the clinical practice. PMID- 26840452 TI - Disparate access to treatment regimens in chronic hepatitis C patients: data from the TRIO network. AB - Despite the clinical success in the real-world of all oral hepatitis C virus (HCV) therapy with response rates approaching that seen in the clinical trials, access has been limited by many payers with discussion of prioritization of treatment based upon AASLD guidelines. We evaluated patients in the TRIO network who were prescribed sofosbuvir (SOF)-based regimens to determine reasons for not starting treatment. Trio Health is a disease management company that works in partnership with academic medical centres, community physicians and specialty pharmacies in the United States to optimize care for HCV. Data for 3841 patients prescribed a sofosbuvir-containing regimen between December 2013 and September 2014 were obtained through this programme. Of the entire group, 315 (8%) patients did not start the prescribed sofosbuvir-containing therapy. A total of 141 (45%) of the nonstart patients had a commercial plan as their primary insurance, 137 (44%) were primarily covered by Medicaid, 17 (5%) were primarily covered by Medicare, and 20 (6%) were either without coverage or coverage was not specified. Reasons for nonstarts were varied and overlapping. Only 15 patients (5% of nonstarts) did not start because they were unreachable or failed to complete required testing. Another 39 patients who did not start (12%) were following their physicians' direction to either wait for new treatment options or to hold treatment for an unspecified reason. Insurance-related processes and financial reasons accounted for 254 (81%) of the 315 nonstarts. The remaining 7 (2%) patients did not have a specified reason for not starting treatment. Nonstart rates were highest in the Medicaid-covered population at 35%. Medicare and Commercial nonstart rates were 2% and 6%, respectively. In a matched comparison, patients with commercial coverage were 6.5 times as likely to start SOF-based therapy compared to patients with Medicaid. Despite high SVR rates of SOF-based regimens in clinical practice, there are still barriers to access to care. In fact, almost half of the nonstart patients had advanced fibrosis scores (F3 or F4) and should have been prioritized to start treatment. As better treatment for HCV with high efficacy and low side effect rates become available, the disparity in access to treatment, as evidenced by the high nonstart rate in the Medicaid covered group, must be resolved. PMID- 26840453 TI - Spatial Distribution of Fungal Communities in an Arable Soil. AB - Fungi are prominent drivers of ecological processes in soils, so that fungal communities across different soil ecosystems have been well investigated. However, for arable soils taxonomically resolved fine-scale studies including vertical itemization of fungal communities are still missing. Here, we combined a cloning/Sanger sequencing approach of the ITS/LSU region as marker for general fungi and of the partial SSU region for arbuscular mycorrhizal fungi (AMF) to characterize the microbiome in different maize soil habitats. Four compartments were analyzed over two annual cycles 2009 and 2010: a) ploughed soil in 0-10 cm, b) rooted soil in 40-50 cm, c) root-free soil in 60-70 cm soil depth and d) maize roots. Ascomycota was the most dominant phylum across all compartments. Fungal communities including yeasts and AMF differed strongly between compartments. Inter alia, Tetracladium, the overall largest MOTU (molecular operational taxonomic unit), occurred in all compartments, whereas Trichosporon dominated all soil compartments. Sequences belonging to unclassified Helotiales were forming the most abundant MOTUs exclusively present in roots. This study gives new insights on spatial distribution of fungi and helps to link fungal communities to specific ecological properties such as varying resources, which characterize particular niches of the heterogeneous soil environment. PMID- 26840456 TI - Gain-of-function miRNA signature by mutant p53 associates with poor cancer outcome. AB - Missense mutation of p53 not only impairs its tumor suppression function, but also causes oncogenic gain of function (GOF). The molecular underpinning of mutant p53 (mutp53) GOF is not fully understood, especially for the potential roles of non-coding genes. Here we identify the microRNA expression profile (microRNAome) of mutp53 on Arg282 by controlled microarray experiments, and clarify the prognostic significance of mutp53-regulated miRNAs in cancers. A predominant repression effect on miRNA expression was found for mutant p53, with 183 significantly downregulated and only 12 upregulated miRNAs. Mutp53 and wild type (wtp53) commonly upregulate let-7i, and other two miRNAs were upregulated by wtp53 but repressed by mutp53 (miR-610 and miR-3065-3p). Based the mutp53 regulated miRNA signature, a non-negative matrix factorization (NMF) model classified gastric cancer (GC) cases into subgroups with significantly different Disease-free survival (Kaplan-Meier test, P = 0.013). In contrast, the NMF model based on all miRNAs did not associate with cancer outcome. The mutp53 miRNA signature associated with the outcomes of breast cancer (P = 0.024) and hepatocellular cancer (P = 0.012). The miRPath analysis revealed that mutp53 suppressed miRNAs associate with Hippo, TGF-beta and stem cell signaling pathways. Taken together, our results highlight a miRNA-mediated GOF mechanism of mutant p53 on Arg282, and suggest the prognostic potential of mutp53-associated miRNA signature. PMID- 26840455 TI - Setdb1, a novel interactor of DeltaNp63, is involved in breast tumorigenesis. AB - DeltaNp63 has been recently involved in self-renewal potential of breast cancer stem cells. Although the p63 transcriptional profile has been extensively characterized, our knowledge of the p63-binding partners potentially involved in the regulation of breast tumour progression is limited. Here, we performed the yeast two hybrid approach to identify p63alpha interactors involved in breast tumorigenesis and we found that SETDB1, a histone lysine methyl transferases, interacts with DeltaNp63alpha and that this interaction contributes to p63 protein stability. SETDB1 is often amplified in primary breast tumours, and its depletion confers to breast cancer cells growth disadvantage. We identified a list of thirty genes repressed by DeltaNp63 in a SETDB1-dependent manner, whose expression is positively correlated to survival of breast cancer patients. These results suggest that p63 and SETDB1 expression, together with the repressed genes, may have diagnostic and prognostic potential. PMID- 26840454 TI - Germline polymorphisms in an enhancer of PSIP1 are associated with progression free survival in epithelial ovarian cancer. AB - Women with epithelial ovarian cancer (EOC) are usually treated with platinum/taxane therapy after cytoreductive surgery but there is considerable inter-individual variation in response. To identify germline single-nucleotide polymorphisms (SNPs) that contribute to variations in individual responses to chemotherapy, we carried out a multi-phase genome-wide association study (GWAS) in 1,244 women diagnosed with serous EOC who were treated with the same first line chemotherapy, carboplatin and paclitaxel. We identified two SNPs (rs7874043 and rs72700653) in TTC39B (best P=7x10-5, HR=1.90, for rs7874043) associated with progression-free survival (PFS). Functional analyses show that both SNPs lie in a putative regulatory element (PRE) that physically interacts with the promoters of PSIP1, CCDC171 and an alternative promoter of TTC39B. The C allele of rs7874043 is associated with poor PFS and showed increased binding of the Sp1 transcription factor, which is critical for chromatin interactions with PSIP1. Silencing of PSIP1 significantly impaired DNA damage-induced Rad51 nuclear foci and reduced cell viability in ovarian cancer lines. PSIP1 (PC4 and SFRS1 Interacting Protein 1) is known to protect cells from stress-induced apoptosis, and high expression is associated with poor PFS in EOC patients. We therefore suggest that the minor allele of rs7874043 confers poor PFS by increasing PSIP1 expression. PMID- 26840457 TI - Nogo-B receptor promotes the chemoresistance of human hepatocellular carcinoma via the ubiquitination of p53 protein. AB - Nogo-B receptor (NgBR), a type I single transmembrane domain receptor is the specific receptor for Nogo-B. Our previous work demonstrated that NgBR is highly expressed in breast cancer cells, where it promotes epithelial mesenchymal transition (EMT), an important step in metastasis. Here, we show that both in vitro and in vivo increased expression of NgBR contributes to the increased chemoresistance of Bel7402/5FU cells, a stable 5-FU (5-Fluorouracil) resistant cell line related Bel7402 cells. NgBR knockdown abrogates S-phase arrest in Bel7402/5FU cells, which correlates with a reduction in G1/S phase checkpoint proteins p53 and p21. In addition, NgBR suppresses p53 protein levels through activation of the PI3K/Akt/MDM2 pathway, which promotes p53 degradation via the ubiquitin proteasome pathway and thus increases the resistance of human hepatocellular cancer cells to 5-FU. Furthermore, we found that NgBR expression is associated with a poor prognosis of human hepatocellular carcinoma (HCC) patients. These results suggest that targeting NgBR in combination with chemotherapeutic drugs, such as 5-FU, could improve the efficacy of current anticancer treatments. PMID- 26840458 TI - Generation of functional hepatocytes from human spermatogonial stem cells. AB - To generate functional human hepatocytes from stem cells and/or extra-hepatic tissues could provide an important source of cells for treating liver diseases. Spermatogonial stem cells (SSCs) have an unlimited plasticity since they can dedifferentiate and transdifferentiate to other cell lineages. However, generation of mature and functional hepatocytes from human SSCs has not yet been achieved. Here we have for the first time reported direct transdifferentiation of human SSCs to mature and functional hepatocytes by three-step induction using the defined condition medium. Human SSCs were first transdifferentiated to hepatic stem cells, as evidenced by their morphology and biopotential nature of co expressing hepatocyte and cholangiocyte markers but not hallmarks for embryonic stem cells. Hepatic stem cells were further induced to differentiate into mature hepatocytes identified by their morphological traits and strong expression of CK8, CK18, ALB, AAT, TF, TAT, and cytochrome enzymes rather than CK7 or CK19. Significantly, mature hepatocytes derived from human SSCs assumed functional attributes of human hepatocytes, because they could produce albumin, remove ammonia, and uptake and release indocyanine green. Moreover, expression of beta CATENIN, HNF4A, FOXA1 and GATA4 was upregulated during the transdifferentiation of human SSCs to mature hepatocytes. Collectively, human SSCs could directly transdifferentiate to mature and functional hepatocytes. This study could offer an invaluable source of human hepatocytes for curing liver disorders and drug toxicology screening and provide novel insights into mechanisms underlying human liver regeneration. PMID- 26840459 TI - Can Spectral CT Imaging Improve the Differentiation between Malignant and Benign Solitary Pulmonary Nodules? AB - PURPOSE: To quantitatively assess the value of dual-energy CT (DECT) in differentiating malignancy and benignity of solitary pulmonary nodules. MATERIALS AND METHODS: Sixty-three patients with solitary pulmonary nodules detected by CT plain scan underwent contrast enhanced CT scans in arterial phase (AP) and venous phase (VP) with spectral imaging mode for tumor type differentiation. The Gemstone Spectral Imaging (GSI) viewer was used for image display and data analysis. Region of interest was placed on the relatively homogeneous area of the nodule to measure iodine concentration (IC) on iodine-based material decomposition images and CT numbers on monochromatic image sets to generate spectral HU curve. Normalized IC (NIC), slope of the spectral HU curve (lambdaHU) and net CT number enhancement on 70keV images were calculated. The two-sample t test was used to compare quantitative parameters. Receiver operating characteristic curves were generated to calculate sensitivity and specificity. RESULTS: There were 63 nodules, with 37 malignant nodules (59%) and 26 benign nodules (41%). NIC, lambdaHU and net CT number enhancement on 70keV images for malignant nodules were all greater than those of benign nodules. NIC and lambdaHU had intermediate to high performances to differentiate malignant nodules from benign ones with the areas under curve of 0.89 and 0.86 respectively in AP, 0.96 and 0.89 respectively in VP. Using 0.30 as a threshold value for NIC in VP, one could obtain sensitivity of 93.8% and specificity of 85.7% for differentiating malignant from benign solitary pulmonary nodules. These values were statistically higher than the corresponding values of 74.2% and 53.8% obtained with the conventional CT number enhancement. CONCLUSIONS: DECT imaging with GSI mode provides more promising value in quantitative way for distinguishing malignant nodules from benign ones than CT enhancement numbers. PMID- 26840461 TI - Clinical Presentation and Outcomes by Sex in Arrhythmogenic Right Ventricular Cardiomyopathy: Findings from the North American ARVC Registry. AB - BACKGROUND: Sex differences in clinical presentation and outcomes of hereditary arrhythmias are commonly reported. We aimed to compare clinical presentation and outcomes in men and women with arrhythmogenic right ventricular cardiomyopathy (ARVC) enrolled in the North American ARVC Registry. METHODS: A total of 125 ARVC probands (55 females, mean age 38 +/- 12; 70 males, mean age 41 +/- 15) diagnosed, as either "affected" or "borderline" were included. Baseline clinical characteristics and time-dependent outcomes including syncope, ventricular tachycardia (VT), fast VT (>240 bpm), ventricular fibrillation (VF), and death were compared between males and females. RESULTS: The percentage of ARVC subjects diagnosed as "affected" (84% vs. 89%; P = 0.424) or "borderline" (16% vs. 11%; P = 0.424) was similar between females and males. Among the baseline characteristics, inverted T-waves in V2 trended to be more common in women (P = 0.09), whereas abnormal signal-averaged ECGs (SAECGs; P < 0.001) and inducible VT/VF (P = 0.026) were more frequent in men. During a mean follow-up of 37 +/- 20 months, the probability of ICD-recorded VT/VF or death was not significantly different between men and women (P = 0.456). However, there was a trend toward lower risk of fast VT/VF or death in women compared to men (hazard ratio 0.41, 95% CI 0.151-1.113, P = 0.066). Abnormal SAECG and evidence of intramyocardial fat by cardiac MRI was associated with adverse outcomes in men (P = 0.006 and 0.02 respectively). CONCLUSION: In the North American ARVC Registry, we found similar frequency of "affected" and "borderline" subjects between men and women. Sex-related differences were observed in baseline ECG, SAECG, Holter-recorded ventricular arrhythmias, and VT inducibility. Men showed a trend toward greater risk of fast VT than women. PMID- 26840464 TI - TREATMENT OF ANEMIA AND IMPROVEMENT OF QUALITY OF LIFE AMONG PATIENTS WITH CROHN'S DISEASE: experience using ferric carboxymaltose. AB - OBJECTIVES: Anemia is the most common hematological alteration in patients with Crohn's disease, and is frequently related to intestinal inflammatory activity. Its cause is multifactorial and mostly associated with absolute iron deficiency (iron deficiency anemia) and/or functional iron deficiency (inflammation anemia or anemia of chronic disease). It may also be identified through other causes, such as folic acid or vitamin B12 deficiency and secondary to adverse effects from medications (salicylic derivatives and immunosuppressive drugs). In the present study, patients with active Crohn's disease and anemia were evaluated and treated with intravenous ferric carboxymaltose. We discuss the therapeutic schemes (doses), safety, results and improvement of quality of life. METHODS: In the present prospective study, 10 consecutive patients with Crohn's disease, with moderate to severe activity, with anemia (Hb: 6.7 to 10 g/dL), who were attended between March 2014 and March 2015, were evaluated. Six (60%) were men and four were women, all with moderate or severe anemia (hemoglobin <10 g/dL). They were treated with a maximum of three intravenous infusions of 1000 mg of ferric carboxymaltose, of at least 15 minutes in duration. It was also sought to correlate the inflammatory Crohn's disease activity degree (measured using the Crohn's Disease Activity Index, CDAI) and C-reactive protein level with the severity of anemia. The primary outcome was an increase in Hb of >=2 g/dL and the secondary outcome was the normalization of anemia (Hb >=12 g/dL for women and >=13 g/dL for men) and the improvement in quality of life seen 12 weeks after the last application of carboxymaltose. RESULTS: Among the 10 patients studied, parenteral iron supplementation was administered in three cases during hospitalization and the others received this on an outpatient basis. The total iron dose ranged from 1,000 to 2,000 mg, with an average of 1,650 mg. Crohn's disease activity measured using CDAI and C-reactive protein correlated with the intensity of anemia. An increase of 2 g/dL occurred in eight (80%) patients after 12 weeks and normalization of anemia was found in seven (70%) patients. Improvements in quality-of-life scores were found for all (100%) patients after 12 weeks. Carboxymaltose was well tolerated. Three patients presented adverse reactions (two with nausea and one with headache) of mild intensity. CONCLUSIONS: Anemia is a frequent complication for Crohn's disease patients. Intravenous iron therapy has been recommended for Crohn's disease patients, because for these patients, oral iron absorption is very limited. This is because of the inflammatory state and "blocking" of iron entry into enterocytes through hepcidin action on ferroportin, along with the elevated rates of gastrointestinal adverse events that compromise adherence to treatment and possibly aggravate the intestinal inflammatory state. The degree of Crohn's disease activity, as measured using CDAI and C-reactive protein, correlates with the severity of anemia. Carboxymaltose is a safe drug, which can be administrated in high doses (up to 1,000 mg per application per week) and corrects anemia and iron stocks over a short period of time, with consequent improvement in quality of life. PMID- 26840462 TI - Alterations of the Ileal and Colonic Mucosal Microbiota in Canine Chronic Enteropathies. AB - BACKGROUND: The intestinal microbiota is increasingly linked to the pathogenesis of chronic enteropathies (CE) in dogs. While imbalances in duodenal and fecal microbial communities have been associated with mucosal inflammation, relatively little is known about alterations in mucosal bacteria seen with CE involving the ileum and colon. AIM: To investigate the composition and spatial organization of mucosal microbiota in dogs with CE and controls. METHODS: Tissue sections from endoscopic biopsies of the ileum and colon from 19 dogs with inflammatory bowel disease (IBD), 6 dogs with granulomatous colitis (GC), 12 dogs with intestinal neoplasia, and 15 controls were studied by fluorescence in situ hybridization (FISH) on a quantifiable basis. RESULTS: The ileal and colonic mucosa of healthy dogs and dogs with CE is predominantly colonized by bacteria localized to free and adherent mucus compartments. CE dogs harbored more (P < 0.05) mucosal bacteria belonging to the Clostridium-coccoides/Eubacterium rectale group, Bacteroides, Enterobacteriaceae, and Escherichia coli versus controls. Within the CE group, IBD dogs had increased (P < 0.05) Enterobacteriaceae and E. coli bacteria attached onto surface epithelia or invading within the intestinal mucosa. Bacterial invasion with E. coli was observed in the ileal and colonic mucosa of dogs with GC (P < 0.05). Dogs with intestinal neoplasia had increased (P < 0.05) adherent (total bacteria, Enterobacteriaceae, E. coli) and invasive (Enterobacteriaceae, E. coli, and Bacteroides) bacteria in biopsy specimens. Increased numbers of total bacteria adherent to the colonic mucosa were associated with clinical disease severity in IBD dogs (P < 0.05). CONCLUSION: Pathogenic events in canine CE are associated with different populations of the ileal and colonic mucosal microbiota. PMID- 26840465 TI - LOWER LEVELS OF VITAMIN D CORRELATE WITH CLINICAL DISEASE ACTIVITY AND QUALITY OF LIFE IN INFLAMMATORY BOWEL DISEASE. AB - BACKGROUND: Inflammatory bowel disease, comprising Crohn's disease and ulcerative colitis, is a group of debilitating conditions associated with deregulated mucosal immune response. Vitamin D has been implicated in immune response and gastrointestinal function. OBJECTIVES: To investigate the correlation between serum vitamin D levels and disease activity and quality of life in patients with inflammatory bowel disease. METHODS: This cross-sectional study enrolled ambulatory patients with inflammatory bowel disease and assessed clinical disease activity and quality of life (Short Inflammatory Bowel Disease Questionnaire [SIBDQ]). Vitamin D levels were determined via serum 25-hydroxyvitamin D measurement; deficiency was defined as values <20 ng/mL. Statistical analysis was performed with SPSS vs 20.0. RESULTS: A total of 76 patients were enrolled, 19 with ulcerative colitis (25%) and 57 with Crohn's disease (75%). Overall, mean serum 25-hydroxyvitamin D levels were low (26.0+/-10.0 ng/mL), while those in patients with Crohn's disease were significantly lower than ulcerative colitis (24.6+/-8.0 vs 30.0+/-12.5 ng/mL; P=0.032). Vitamin D deficiency was found in 30% of patients. Patients who were in clinical remission were found to have higher levels of vitamin D than those who were not in remission (28.0+/-10.3 vs 21.6+/ 6.0 ng/mL, P=0.001). Inflammatory bowel disease patients with SIBDQ scores <50 were found to have significantly lower mean vitamin D levels compared with patients who had SIBDQ scores >=50 (23.4+/-6.9 vs 27.9+/-10.8 ng/mL, P=0.041). CONCLUSIONS: A high proportion of patients with inflammatory bowel disease were vitamin D deficient, particularly patients with Crohn's disease. Both clinical disease activity and quality of life correlated significantly with lower levels of vitamin D, illustrating a clear need for supplementation in patients with inflammatory bowel disease. PMID- 26840460 TI - Multi-Drug Resistance Transporters and a Mechanism-Based Strategy for Assessing Risks of Pesticide Combinations to Honey Bees. AB - Annual losses of honey bee colonies remain high and pesticide exposure is one possible cause. Dangerous combinations of pesticides, plant-produced compounds and antibiotics added to hives may cause or contribute to losses, but it is very difficult to test the many combinations of those compounds that bees encounter. We propose a mechanism-based strategy for simplifying the assessment of combinations of compounds, focusing here on compounds that interact with xenobiotic handling ABC transporters. We evaluate the use of ivermectin as a model substrate for these transporters. Compounds that increase sensitivity of bees to ivermectin may be inhibiting key transporters. We show that several compounds commonly encountered by honey bees (fumagillin, Pristine, quercetin) significantly increased honey bee mortality due to ivermectin and significantly reduced the LC50 of ivermectin suggesting that they may interfere with transporter function. These inhibitors also significantly increased honey bees sensitivity to the neonicotinoid insecticide acetamiprid. This mechanism-based strategy may dramatically reduce the number of tests needed to assess the possibility of adverse combinations among pesticides. We also demonstrate an in vivo transporter assay that provides physical evidence of transporter inhibition by tracking the dynamics of a fluorescent substrate of these transporters (Rhodamine B) in bee tissues. Significantly more Rhodamine B remains in the head and hemolymph of bees pretreated with higher concentrations of the transporter inhibitor verapamil. Mechanism-based strategies for simplifying the assessment of adverse chemical interactions such as described here could improve our ability to identify those combinations that pose significantly greater risk to bees and perhaps improve the risk assessment protocols for honey bees and similar sensitive species. PMID- 26840466 TI - HELICOBACTER PYLORI INFECTION IN PATIENTS WITH DIFFERENT GASTROINTESTINAL DISEASES FROM NORTHERN BRAZIL. AB - BACKGROUND: The mechanisms whereby Helicobacter pylori produces different pathological manifestations in the stomach and duodenum are not fully understood. Considering the geographic diversity in the prevalence of virulence factors of this microorganism and their association with the development of different diseases, the search for pathogenicity markers such as CagA and VacA alleles by molecular techniques has intensified. OBJECTIVES: To investigate the presence of H. pylori infection and the frequency of different genotypes of this bacterium in patients with gastrointestinal diseases from Northern Brazil, and to establish their association with the histopathological findings. METHODS: In a prospective study, samples were collected from 554 patients with different gastrointestinal diseases (gastritis, duodenal ulcer, gastric ulcer, and gastric cancer) seen at a referral hospital attending the entire State of Para, located in the metropolitan region of Belem. Data such as gender and age obtained with an epidemiological questionnaire were analyzed. The presence of H. pylori and the bacterial genotype were investigated by PCR. Gastric biopsies were assessed histologically. RESULTS: The prevalence of H. pylori infection was 91%. Infection was more frequent among patients with gastric ulcer and gastric cancer. In these groups, there was a predominance of men and older patients when compared to the other two groups studied. The predominant bacterial genotype was s1m1cagA+, which was more frequent among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between s1m1cagA+ strains and a higher degree of inflammation, neutrophil activity and development of intestinal metaplasia. CONCLUSION: The present study demonstrates a high incidence of H. pylori infection in the patients analyzed, especially among those with gastric ulcer and gastric cancer. Virulent s1m1cagA+ strains predominated and were associated with more severe lesions. PMID- 26840467 TI - INCREASED TISSUE TRANSGLUTAMINASE LEVELS ARE ASSOCIATED WITH INCREASED EPILEPTIFORM ACTIVITY IN ELECTROENCEPHALOGRAPHY AMONG PATIENTS WITH CELIAC DISEASE. AB - BACKGROUND: Celiac disease is an autoimmune systemic disorder in genetically predisposed individuals precipitated by gluten ingestion. OBJECTIVE: In this study, we aimed to determine asymptomatic spike-and-wave findings on electroencephalography in children with celiac disease. METHODS: A total of 175 children with the diagnosis of celiac disease (study group) and 99 age- and sex matched healthy children as controls (control group) were included in the study. In order to determine the effects of gluten free diet on laboratory and electroencephalography findings, the celiac group is further subdivided into two as newly-diagnosed and formerly-diagnosed patients. Medical histories of all children and laboratory findings were all recorded and neurologic statuses were evaluated. All patients underwent a sleep and awake electroencephalography. RESULTS: Among 175 celiac disease patients included in the study, 43 were newly diagnosed while 132 were formerly-diagnosed patients. In electroencephalography evaluation of patients the epileptiform activity was determined in 4 (9.3%) of newly diagnosed and in 2 (1.5%) of formerly diagnosed patients; on the other hand the epileptiform activity was present in only 1 (1.0%) of control cases. There was a statistically significant difference between groups in regards to the presence of epileptiform activity in electroencephalography. Pearson correlation analysis revealed that epileptiform activity in both sleep and awake electroencephalography were positively correlated with tissue transglutaminase levels (P=0.014 and P=0.019, respectively). CONCLUSION: We have determined an increased epileptiform activity frequency among newly-diagnosed celiac disease patients compared with formerly-diagnosed celiac disease patients and control cases. Moreover the tissue transglutaminase levels were also correlated with the presence of epileptiform activity in electroencephalography. Among newly diagnosed celiac disease patients, clinicians should be aware of this association and be alert about any neurological symptoms. PMID- 26840468 TI - THE PREVALENCE OF CELIAC DISEASE IN PATIENTS WITH IRON-DEFICIENCY ANEMIA IN CENTER AND SOUTH AREA OF IRAN. AB - BACKGROUND: Celiac disease is an immune-mediated enteropathy due to a permanent sensitivity to gluten in genetically susceptible people. Iron-deficiency anemia is the most widely experienced anemia in humans. Iron-deficiency anemia additionally is a common extra intestinal manifestation of celiac disease. OBJECTIVE: To investigate correlation between tTg levels and histological alterations and then to determine the prevalence of celiac disease in Center and South area patients of Iran with iron deficiency anemia. METHODS: A total of 402 patients aged 12-78 years who presented with iron-deficiency anemia were included in this study. Hemoglobin, mean corpuscular volume and serum ferritin were determined. Venous blood samples for anti-tissue transglutaminase antibody immunoglobuline A and G were obtained from these patients. Upper gastrointestinal endoscopy was recommended to patients who had positive serology. RESULTS: Of 402 patients with iron-deficiency anemia, 42 (10.4%) had positive serology for celiac disease. The small intestine biopsy of all patients with positive serology showed pathological changes (Marsh I, II & III). There was not significant difference in the mean hemoglobin level between iron-deficiency anemia patients with celiac disease and without celiac disease, duodenal biopsy results did not show significant relationship between the severity of pathological changes and levels of anti-tTG IgG (P -value: 0/869) but significant relationship was discovered between pathological changes and levels of anti-tTG IgA (P -value: 0/004). CONCLUSION: Screening of celiac disease by anti-tissue transglutaminase antibody should be completed as a routine investigation in patients with iron-deficiency anemia. Also physicians must consider celiac disease as a possible reason of anemia in all patients with iron deficiency anemia. PMID- 26840469 TI - PROPOSAL OF A CLINICAL CARE PATHWAY FOR THE MANAGEMENT OF ACUTE UPPER GASTROINTESTINAL BLEEDING. AB - BACKGROUND: Upper gastrointestinal bleeding implies significant clinical and economic repercussions. The correct establishment of the latest therapies for the upper gastrointestinal bleeding is associated with reduced in-hospital mortality. The use of clinical pathways for the upper gastrointestinal bleeding is associated with shorter hospital stay and lower hospital costs. OBJECTIVE: The primary objective is the development of a clinical care pathway for the management of patients with upper gastrointestinal bleeding, to be used in tertiary hospital. METHODS: It was conducted an extensive literature review on the management of upper gastrointestinal bleeding, contained in the primary and secondary information sources. RESULTS: The result is a clinical care pathway for the upper gastrointestinal bleeding in patients with evidence of recent bleeding, diagnosed by melena or hematemesis in the last 12 hours, who are admitted in the emergency rooms and intensive care units of tertiary hospitals. In this compact and understandable pathway, it is well demonstrated the management since the admission, with definition of the inclusion and exclusion criteria, passing through the initial clinical treatment, posterior guidance for endoscopic therapy, and referral to rescue therapies in cases of persistent or rebleeding. It was also included the care that must be taken before hospital discharge for all patients who recover from an episode of bleeding. CONCLUSION: The introduction of a clinical care pathway for patients with upper gastrointestinal bleeding may contribute to standardization of medical practices, decrease in waiting time for medications and services, length of hospital stay and costs. PMID- 26840470 TI - HUMAN DNA QUANTIFICATION IN THE STOOLS OF PATIENTS WITH COLORECTAL CANCER. AB - BACKGROUND: Colorectal cancer is one of the main cause of cancer in the world. Colonoscopy is the best screen method, however the compliance is less than 50%. Quantification of human DNA (hDNA) in the feces may be a possible screen non invasive method that is a consequence of the high proliferation and exfoliation of cancer cells. OBJECTIVE: To quantify the human DNA in the stools of patients with colorectal cancer or polyps. METHODS: Fifty patients with CRC, 26 polyps and 53 with normal colonoscopy were included. Total and human DNA were analyzed from the frozen stools. RESULTS: An increased concentration of hDNA in the stools was observed in colorectal cancer patients compared to controls and polyps. Tumors localized in the left side of the colon had higher concentrations of hDNA. There were no difference between polyps and controls. A cut off of 0.87 ng/mL of human DNA was determined for colorectal cancer patients by the ROC curve, with a sensitivity of 66% and a specificity of 86.8%. For polyps the cut off was 0.41, the sensitivity was 41% and the specificity 77.4%. CONCLUSION: A higher concentration of hDNA had been found in colorectal cancer patients The quantification of hDNA from the stools can be a trial method for the diagnosis of colorectal cancer. PMID- 26840471 TI - RESULTS OF POSTERIOR MYECTOMY FOR THE TREATMENT OF CHILDREN WITH CHRONIC CONSTIPATION. AB - BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the result of posterior myectomy in children with chronic constipation who underwent to this surgery. METHODS: Forty eight children with chronic constipation who did not respond to diet, laxative, or enema were included. Children with abnormal barium enema showing transitional zone were excluded. Children with documented metabolic disease diabetes, and hypothyroidism were also excluded. All patients underwent posterior myectomy. Children were followed during 1 year after surgery regarding frequency of fecal evacuation, fecal consistency, straining during defecation, and diameter of feces. Data was analyzed using SPSS version 13.0 (Chicago, IL, USA). RESULTS: Of 48 cases that underwent surgery, 21 were male and 27 were female. Age range was 1.5 to 11 years old. Mean duration of constipation before surgery was 22.79+/-17.08 (range 6-48 months). Mean duration of medical treatment was 14.90+/-10.31 (range= 6-48 months). Fecal consistency, feces diameter, number of bowel movements and straining during defecation were compared before and after surgery. The results were statistically significant ( P <0.001). Of all cases, 52% continued treatment of constipation after surgery for 1 year. Ganglion cells were absent in 32 cases. Ganglion cells were present in seven children. Proximal ganglion cell was found in nine cases Treatment response was not different between cases according to status of ganglion cell in biopsy. CONCLUSION: Fecal consistency, feces diameter, number of bowel movements, and straining for defecation were improved after posterior myectomy. Another study with more sample is required for better evaluation of treatment. PMID- 26840472 TI - CLINICAL, EPIDEMIOLOGIC, AND ENDOSCOPIC PROFILE IN CHILDREN AND ADOLESCENTS WITH COLONIC POLYPS IN TWO REFERENCE CENTERS. AB - BACKGROUND: The main goal of this paper is to investigate the frequency, clinical profile, and endoscopic findings of children and teenagers submitted to colonoscopies. METHODS: Patients of below 18 years of age, diagnosed with polyps by means of colonoscopies at two reference centers of pediatric endoscopy were followed-up between 2002 and 2012. The clinical variables evaluated in this study included: gender, recommendation of colonoscopy, associated signs and symptoms, age of onset of symptoms, age at identification of the polyp, interval of time between the onset of symptoms and the endoscopic diagnosis of colonic polyps, and family history of intestinal polyposis and/or colorectal cancer. The characteristics of the polyps also included: number, morphological type, histology, and distribution. Polyposis syndromes were also investigated. RESULTS: From the 233 patients submitted to colonoscopies, polyps were found in 74 (31.7%) patients, with a median age of 6.6 years, of which 61% were male. Juvenile polyps were identified in 55 (74%) patients, with 7 (9%) characterized within the criteria for juvenile polyposis. Patients with intestinal polyposis syndromes were diagnosed in 35% of the patients. The most frequent clinical presentation was hematochezia. Abdominal pain with acute episodes of intestinal partial obstruction or intussusception with emergency laparotomy was observed in the majority of Peutz-Jeghers syndrome patients leading to an increased morbidity. CONCLUSIONS: Even though juvenile colonic polyps are the most frequent type of diagnosed polyps, the present study identified a significant level of children with polyposis syndromes (35%), associated with a higher morbidity of these individuals. PMID- 26840473 TI - BOWEL PREPARATION BEFORE COLONOSCOPY FOR CHILDREN: comparison of efficacy of three different methods. AB - BACKGROUND: Colonoscopy is an important diagnostic and therapeutic procedure. Adequate bowel preparation is mandatory. Several regimens were discussed in the literature. Among the drugs which has recently used, polyethylene glycol is one of the most popular agents. OBJECTIVES: The aim of this study was to compare efficacy of three different methods for 1 day preparation before colonoscopy. METHODS: This study included children with the range of ages (2-21) who had an indication of colonoscopy. Exclusion criteria were based on the history of previous surgery, parental disagreement, and patients who did not use preparation protocol. Three methods for bowel preparation were studied: 1- Polyethylene glycol only; 2- Polyethylene glycol and bisacodyl suppositories; 3- Polyethylene glycol plus normal saline enema. Boston Bowel Preparation Score was used for evaluation of preparation. SPSS version 16.0 (Chicago, IL, USA) were used for data analysis. RESULTS: In this study 83 cases completed the bowel preparation completely. Acceptable bowel preparation was seen in 24 (85.71%), 36 (94.73%), and 14 (82.35%) of cases in PEG, PEG + bisacodyl, and PEG + normal saline enema groups respectively. PEG + bisacodyl suppositories was more effective than PEG + normal saline for the preparation of the first segment ( P=0.05). For second and third segment of colon, BPPS score was higher in PEG + bisacodyl suppositories compared to other regimens, but this difference was not statistically significant. CONCLUSION: There was no significant difference between 1 day colonoscopy regimens in terms of bowel preparation score. Lowest score was seen in PEG + enema group compared to other group. PMID- 26840474 TI - ASSOCIATION OF THE NUTRITIONAL PROFILE WITH HISTOLOGICAL FINDINGS OF PATIENTS WITH GENOTYPE 1 CHRONIC HEPATITIS C INFECTION. AB - BACKGROUND: Different factors are responsible for the progression of hepatic fibrosis in chronic infection with hepatitis C virus, but the role of nutritional factors in the progression of the disease is not clearly defined. This study aimed to evaluate the nutritional status and dietary profile among patients with chronic hepatitis C who were candidates for treatment and its association with histopathological features. METHODS: A crossectional study was conducted on treatment-naive patients with chronic hepatitis C genotype 1, between 2011 and 2013. The following assessments were performed before treatment: liver biopsy, anthropometric measurements and qualitative/quantitative analysis of food intake. RESULTS: Seventy patients were studied. The majority of patients was classified as obese (34%) or overweight (20%) according to body mass index [BMI] and as at risk for cardiovascular diseases by waist circumference (79%). Unhealthy food intake was presented by 59% according to qualitative parameters and several patients showed an insufficient intake of calories (59%), excessive intake of protein (36%) and of saturated fat (63%), according to quantitative analysis. With respect to histology, 68% presented activity grade >=2, 65% had steatosis and 25% exhibited fibrosis stage >2. Comparative analysis between anthropometric parameters and histological features showed that elevated waist circumference was the only variable associated to hepatic steatosis ( P =0.05). There was no association between qualitative and quantitative food intake parameters with histological findings. CONCLUSION: In this study, most of the patients with hepatitis C presented inadequate qualitative food intake and excessive consumption of saturated fat; in addition, excess of abdominal fat was associated to hepatic steatosis. Therefore, nutritional guidance should be implemented prior to treatment in patients with chronic hepatitis C, in order to avoid nutritional disorders and negative impact on the management of patients. PMID- 26840475 TI - CROSS SECTIONAL STUDY OF PREVALENCE AND RISK FACTORS OF HEPATITIS B AND HEPATITIS C INFECTION IN A RURAL VILLAGE OF INDIA. AB - BACKGROUND: Hepatitis B virus and hepatitis C virus are among the principal causes of severe liver disease. There is limited data of epidemiology of Hepatitis B in community, more so in rural population. OBJECTIVE: To find the prevalence of hepatitis B and C infection in community and study the risk factors for their transmission. METHODS: This was a community based cross sectional study. A total of 1833 randomly selected subjects from a rural area were interviewed for risk factors for transmission and tested for markers of hepatitis B and hepatitis C infection. All the positive card tests were confirmed by ELISA. RESULTS: Out of 2400 subjects, rate for participation was 76.38%. None of the subjects was positive for anti hepatitis C virus antibody. Point prevalence for HBsAg positivity was 0.92. Being healthcare worker and having tattoo were significantly associated with HBsAg positive results. Nose and ear piercing was reported by almost. History of blood or blood product transfusion, I/V drug abuse, multiple sexual partners, unsafe Injections, hemodialysis and any h/o surgery was not associated with HBsAg positivity. CONCLUSION: Health care workers are at high risk for transmission of hepatitis B. Educating common people regarding mode of transmission of Hepatitis B and C will help to reduce their transmission. PMID- 26840476 TI - ASSOCIATION BETWEEN MURINE DOUBLE MINUTE 2 - T309G polymorphism and recurrence of hepatocellular carcinoma after surgical treatment. AB - BACKGROUND: Discovery and incorporation of biomarker panels to cancer studies enabled the understanding of genetic variation and its interference in carcinogenesis at molecular level. The potential association between single nucleotide polymorphism (SNP) 309 and increased development of tumors, such as hepatocellular carcinoma, has been subject to several studies. This is the first study on this association conducted in Brazil. METHODS: 62 cases of cirrhotic patients with hepatocellular carcinoma surgically treated by partial hepatectomy (HPT) or by liver transplantation (LTX) from 2000 to 2009 at Santa Casa Hospital Complex, in the city of Porto Alegre, were retrospectively analyzed. Tumor samples from surgical specimen were collected and prepared for study in paraffin blocks. RESULTS: Overall survival was 26.7 months in the HPT group and 62.4 months in the LTX group (P <0.01). Overall tumor recurrence was 66.7% in the HPT group (10/15) and 17% in the LTX group (8/47) (X2=13.602, P <0.01). Alpha fetoprotein levels >200ng/mL, microvascular invasion and histological grade were associated with tumor recurrence (P <0.01). Recurrence rates in each surgical group and analysis of factors associated with tumor recurrence, when stratified for each genotypic pattern, were both not statistically significant. CONCLUSION: G/G genotype was not associated with tumor recurrence after surgical treatment and it did not show any correlation with other prognostic factors. PMID- 26840477 TI - THE INTESTINAL MICROBIOTA AND THE ROLE OF PROBIOTICS IN IRRITABLE BOWEL SYNDROME: a review. AB - Irritable bowel syndrome is a common, chronic relapsing gastrointestinal disorder that affects 7%-22% of the population worldwide. According to Rome III Criteria, the disorder is defined by the coexistence of abdominal discomfort or pain associated with an alteration in bowel habits. Its pathophysiology is not completely understood but, in addition to some important abnormalities, the disturbed intestinal microbiota has also been described supported by several strands of evidence. The treatment of irritable bowel syndrome is based upon several therapeutic approaches but few have been successful or without adverse events and more recently the gut microbiota and the use of probiotics have emerged as a factor to be considered. Probiotics are live micro-organisms which when consumed in adequate amounts confer a health benefit to the host, such as Lactic bacteria among others. An important scientific rationale has emerged for the use of probiotics in irritable bowel syndrome, although the data regarding different species are still limited. Not all probiotics are beneficial: it is important to select the specific strain which should be supported by good evidence base. The mechanisms of action of probiotics are described and the main strains are quoted. PMID- 26840478 TI - Belittling of a significant decline in neonatal metabolic acidosis rate achieved by STAN monitoring. PMID- 26840479 TI - Wnt3a, a Protein Secreted by Mesenchymal Stem Cells Is Neuroprotective and Promotes Neurocognitive Recovery Following Traumatic Brain Injury. AB - Intravenous administration of bone marrow derived mesenchymal stem cells (MSCs) has been shown to reduce blood brain barrier compromise and improve neurocognition following traumatic brain injury (TBI). These effects occur in the absence of engraftment and differentiation of these cells in the injured brain. Recent studies have shown that soluble factors produced by MSCs mediate a number of the therapeutic effects. In this study, we sought to determine if intravenous administration of MSCs (IV-MSCs) could enhance hippocampal neurogenesis following TBI. Our results demonstrate that IV-MSC treatment attenuates loss of neural stem cells and promotes hippocampal neurogenesis in TBI injured mice. As Wnt signaling has been implicated in neurogenesis, we measured circulating Wnt3a levels in serum following IV-MSC administration and found a significant increase in Wnt3a. Concurrent with this increase, we detected increased activation of the Wnt/beta catenin signaling pathway in hippocampal neurons. Furthermore, IV recombinant Wnt3a treatment provided neuroprotection, promoted neurogenesis, and improved neurocognitive function in TBI injured mice. Taken together, our results demonstrate a role for Wnt3a in the therapeutic potential of MSCs and identify Wnt3a as a potential stand-alone therapy or as part of a combination therapeutic strategy for the treatment of TBI. Stem Cells 2016;34:1263-1272. PMID- 26840480 TI - Simvastatin Efficiently Lowers Small LDL-IgG Immune Complex Levels: A Therapeutic Quality beyond the Lipid-Lowering Effect. AB - We investigated a polyethylene glycol non-precipitable low-density lipoprotein (LDL) subfraction targeted by IgG and the influence of statin therapy on plasma levels of these small LDL-IgG-immune complexes (LDL-IgG-IC). LDL-subfractions were isolated from 6 atherosclerotic subjects and 3 healthy individuals utilizing iodixanol density gradient ultracentrifugation. Cholesterol, apoB and malondialdehyde (MDA) levels were determined in each fraction by enzymatic testing, dissociation-enhanced lanthanide fluorescence immunoassay and high performance liquid chromatography, respectively. The levels of LDL-IgG-IC were quantified densitometrically following lipid electrophoresis, particle size distribution was assessed with dynamic light scattering and size exclusion chromatography. The influence of simvastatin (40 mg/day for three months) on small LDL-IgG-IC levels and their distribution among LDL-subfractions (salt gradient separation) were investigated in 11 patients with confirmed coronary artery disease (CAD). We demonstrate that the investigated LDL-IgG-IC are small particles present in atherosclerotic patients and healthy subjects. In vitro assembly of LDL-IgG-IC resulted in particle density shifts indicating a composition of one single molecule of IgG per LDL particle. Normalization on cholesterol levels revealed MDA values twice as high for LDL-subfractions rich in small LDL-IgG-IC if compared to dominant LDL-subfractions. Reactivity of affinity purified small LDL-IgG-IC to monoclonal antibody OB/04 indicates a high degree of modified apoB and oxidative modification. Simvastatin therapy studied in the CAD patients significantly lowered LDL levels and to an even higher extent, small LDL IgG-IC levels without affecting their distribution. In conclusion simvastatin lowers levels of small LDL-IgG-IC more effectively than LDL-cholesterol and LDL apoB levels in atherosclerotic patients. This antiatherogenic effect may additionally contribute to the known beneficial effects of this drug in the treatment of atherosclerosis. PMID- 26840482 TI - Evolution: Mitochondria in the second act. PMID- 26840481 TI - A thalamic input to the nucleus accumbens mediates opiate dependence. AB - Chronic opiate use induces opiate dependence, which is characterized by extremely unpleasant physical and emotional feelings after drug use is terminated. Both the rewarding effects of a drug and the desire to avoid withdrawal symptoms motivate continued drug use, and the nucleus accumbens is important for orchestrating both processes. While multiple inputs to the nucleus accumbens regulate reward, little is known about the nucleus accumbens circuitry underlying withdrawal. Here we identify the paraventricular nucleus of the thalamus as a prominent input to the nucleus accumbens mediating the expression of opiate-withdrawal-induced physical signs and aversive memory. Activity in the paraventricular nucleus of the thalamus to nucleus accumbens pathway is necessary and sufficient to mediate behavioural aversion. Selectively silencing this pathway abolishes aversive symptoms in two different mouse models of opiate withdrawal. Chronic morphine exposure selectively potentiates excitatory transmission between the paraventricular nucleus of the thalamus and D2-receptor-expressing medium spiny neurons via synaptic insertion of GluA2-lacking AMPA receptors. Notably, in vivo optogenetic depotentiation restores normal transmission at these synapses and robustly suppresses morphine withdrawal symptoms. This links morphine-evoked pathway- and cell-type-specific plasticity in the paraventricular nucleus of the thalamus to nucleus accumbens circuit to opiate dependence, and suggests that reprogramming this circuit holds promise for treating opiate addiction. PMID- 26840483 TI - Backbone NMR reveals allosteric signal transduction networks in the beta1 adrenergic receptor. AB - G protein-coupled receptors (GPCRs) are physiologically important transmembrane signalling proteins that trigger intracellular responses upon binding of extracellular ligands. Despite recent breakthroughs in GPCR crystallography, the details of ligand-induced signal transduction are not well understood owing to missing dynamical information. In principle, such information can be provided by NMR, but so far only limited data of functional relevance on few side-chain sites of eukaryotic GPCRs have been obtained. Here we show that receptor motions can be followed at virtually any backbone site in a thermostabilized mutant of the turkey beta1-adrenergic receptor (beta1AR). Labelling with [(15)N]valine in a eukaryotic expression system provides over twenty resolved resonances that report on structure and dynamics in six ligand complexes and the apo form. The response to the various ligands is heterogeneous in the vicinity of the binding pocket, but gets transformed into a homogeneous readout at the intracellular side of helix 5 (TM5), which correlates linearly with ligand efficacy for the G protein pathway. The effect of several pertinent, thermostabilizing point mutations was assessed by reverting them to the native sequence. Whereas the response to ligands remains largely unchanged, binding of the G protein mimetic nanobody NB80 and G protein activation are only observed when two conserved tyrosines (Y227 and Y343) are restored. Binding of NB80 leads to very strong spectral changes throughout the receptor, including the extracellular ligand entrance pocket. This indicates that even the fully thermostabilized receptor undergoes activating motions in TM5, but that the fully active state is only reached in presence of Y227 and Y343 by stabilization with a G protein-like partner. The combined analysis of chemical shift changes from the point mutations and ligand responses identifies crucial connections in the allosteric activation pathway, and presents a general experimental method to delineate signal transmission networks at high resolution in GPCRs. PMID- 26840484 TI - Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice. AB - The DNA-binding protein PRDM9 directs positioning of the double-strand breaks (DSBs) that initiate meiotic recombination in mice and humans. Prdm9 is the only mammalian speciation gene yet identified and is responsible for sterility phenotypes in male hybrids of certain mouse subspecies. To investigate PRDM9 binding and its role in fertility and meiotic recombination, we humanized the DNA binding domain of PRDM9 in C57BL/6 mice. This change repositions DSB hotspots and completely restores fertility in male hybrids. Here we show that alteration of one Prdm9 allele impacts the behaviour of DSBs controlled by the other allele at chromosome-wide scales. These effects correlate strongly with the degree to which each PRDM9 variant binds both homologues at the DSB sites it controls. Furthermore, higher genome-wide levels of such 'symmetric' PRDM9 binding associate with increasing fertility measures, and comparisons of individual hotspots suggest binding symmetry plays a downstream role in the recombination process. These findings reveal that subspecies-specific degradation of PRDM9 binding sites by meiotic drive, which steadily increases asymmetric PRDM9 binding, has impacts beyond simply changing hotspot positions, and strongly support a direct involvement in hybrid infertility. Because such meiotic drive occurs across mammals, PRDM9 may play a wider, yet transient, role in the early stages of speciation. PMID- 26840486 TI - Ageing: Out with the old. PMID- 26840487 TI - Genetics: Asymmetric breaks in DNA cause sterility. PMID- 26840488 TI - Climate science: A great Arctic ice shelf. PMID- 26840485 TI - Real-time, portable genome sequencing for Ebola surveillance. AB - The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths. Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 * 10(-3) and 1.42 * 10(-3) mutations per site per year. This is equivalent to 16-27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic. Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions. Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities. To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15-60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks. PMID- 26840491 TI - Covariation of deep Southern Ocean oxygenation and atmospheric CO2 through the last ice age. AB - No single mechanism can account for the full amplitude of past atmospheric carbon dioxide (CO2) concentration variability over glacial-interglacial cycles. A build up of carbon in the deep ocean has been shown to have occurred during the Last Glacial Maximum. However, the mechanisms responsible for the release of the deeply sequestered carbon to the atmosphere at deglaciation, and the relative importance of deep ocean sequestration in regulating millennial-timescale variations in atmospheric CO2 concentration before the Last Glacial Maximum, have remained unclear. Here we present sedimentary redox-sensitive trace-metal records from the Antarctic Zone of the Southern Ocean that provide a reconstruction of transient changes in deep ocean oxygenation and, by inference, respired carbon storage throughout the last glacial cycle. Our data suggest that respired carbon was removed from the abyssal Southern Ocean during the Northern Hemisphere cold phases of the deglaciation, when atmospheric CO2 concentration increased rapidly, reflecting--at least in part--a combination of dwindling iron fertilization by dust and enhanced deep ocean ventilation. Furthermore, our records show that the observed covariation between atmospheric CO2 concentration and abyssal Southern Ocean oxygenation was maintained throughout most of the past 80,000 years. This suggests that on millennial timescales deep ocean circulation and iron fertilization in the Southern Ocean played a consistent role in modifying atmospheric CO2 concentration. PMID- 26840489 TI - Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. AB - Cellular senescence, a stress-induced irreversible growth arrest often characterized by expression of p16(Ink4a) (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK ATTAC, to induce apoptosis in p16(Ink4a)-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16(Ink4a)-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio protective KATP channels and adipocytes, respectively. Thus, p16(Ink4a)-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan. PMID- 26840490 TI - Late acquisition of mitochondria by a host with chimaeric prokaryotic ancestry. AB - The origin of eukaryotes stands as a major conundrum in biology. Current evidence indicates that the last eukaryotic common ancestor already possessed many eukaryotic hallmarks, including a complex subcellular organization. In addition, the lack of evolutionary intermediates challenges the elucidation of the relative order of emergence of eukaryotic traits. Mitochondria are ubiquitous organelles derived from an alphaproteobacterial endosymbiont. Different hypotheses disagree on whether mitochondria were acquired early or late during eukaryogenesis. Similarly, the nature and complexity of the receiving host are debated, with models ranging from a simple prokaryotic host to an already complex proto eukaryote. Most competing scenarios can be roughly grouped into either mito early, which consider the driving force of eukaryogenesis to be mitochondrial endosymbiosis into a simple host, or mito-late, which postulate that a significant complexity predated mitochondrial endosymbiosis. Here we provide evidence for late mitochondrial endosymbiosis. We use phylogenomics to directly test whether proto-mitochondrial proteins were acquired earlier or later than other proteins of the last eukaryotic common ancestor. We find that last eukaryotic common ancestor protein families of alphaproteobacterial ancestry and of mitochondrial localization show the shortest phylogenetic distances to their closest prokaryotic relatives, compared with proteins of different prokaryotic origin or cellular localization. Altogether, our results shed new light on a long standing question and provide compelling support for the late acquisition of mitochondria into a host that already had a proteome of chimaeric phylogenetic origin. We argue that mitochondrial endosymbiosis was one of the ultimate steps in eukaryogenesis and that it provided the definitive selective advantage to mitochondria-bearing eukaryotes over less complex forms. PMID- 26840493 TI - Development of a Method for Transferring Paraplegic Patients with Advanced Cancer from Bed to Wheelchair. AB - BACKGROUND: For patients with traumatic paraplegia, the ability to push up is a prerequisite for basic movements, including the transfer from bed to wheelchair. However, this movement may be contraindicated in patients with advanced cancer with bone metastases because of the risk of pain and pathologic fractures and muscle weakness resulting from cancer cachexia and disuse syndrome. OBJECTIVE: The purpose of this study was to develop a method for transferring paraplegic patients from bed to wheelchair taking into consideration the unique characteristics of patients with advanced cancer with bone metastases and investigate the usefulness of said method. METHODS: We developed a system for safe transfer from bed to wheelchair of paraplegic patients with advanced cancer consisting of horizontal transfer of the patient with safety apparatus utilizing an electric motor and potential energy. This method was used in 25 patients with advanced cancer and paraplegia. The activities of daily living (ADL), success/failure of transfer, ability for overnight stays outside the hospital, and possibility of discharge were investigated. RESULTS: Use of the newly developed transfer method caused no difficulties and the ADL scores were significantly increased (p < 0.001). In all, 64% of the subjects could be transferred successfully from bed to wheelchair; 60% had successful overnight stays outside the hospital, and 48% could be discharged. CONCLUSION: Our findings suggest that the use of our newly devised system enables transfer from bed to wheelchair of even those patients with advanced cancer who cannot resume walking in the upright position because of paraplegia. PMID- 26840492 TI - Antibiotic Resistance of Commensal Staphylococcus aureus and Coagulase-Negative Staphylococci in an International Cohort of Surgeons: A Prospective Point Prevalence Study. AB - Nasal colonization with antibiotic resistant bacteria represents both a risk factor for the colonized individual and their immediate contacts. Despite the fact that healthcare workers such as orthopedic surgeons are at a critical interface between the healthcare environment and an at-risk patient population, the prevalence of antibiotic resistant bacteria within the surgical profession remains unclear. This study offers a snapshot of the rate of nasal colonization of orthopedic surgeons with multi-resistant staphylococci including methicillin resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS). We performed a prospective, observational study obtained at a single time point in late 2013. The participants were active orthopedic, spine and head & neck surgeons from 75 countries. The prevalence of nasal carriage of the different bacteria and the corresponding 95% confidence interval were calculated. From a cohort of 1,166 surgeons, we found an average S. aureus nasal colonization rate of 28.0% (CI 25.4;30.6) and MRSA rate of 2.0% (CI 1.3;2.9), although significant regional variations were observed. The highest rates of MRSA colonization were found in Asia (6.1%), Africa (5.1%) and Central America (4.8%). There was no MRSA carriage detected within our population of 79 surgeons working in North America, and a low (0.6%) MRSA rate in 657 surgeons working in Europe. High rates of MRCoNS nasal carriage were also observed (21.4% overall), with a similar geographic distribution. Recent use of systemic antibiotics was associated with higher rates of carriage of resistant staphylococci. In conclusion, orthopedic surgeons are colonized by S. aureus and MRSA at broadly equivalent rates to the general population. Crucially, geographic differences were observed, which may be partially accounted for by varying antimicrobial stewardship practices between the regions. The elevated rates of resistance within the coagulase-negative staphylococci are of concern, due to the increasing awareness of their importance in hospital acquired and device associated infection. PMID- 26840495 TI - Considerations in Using Serious Videogames as a Method for Providing Diabetes Education. PMID- 26840494 TI - Gadobutrol-Enhanced Magnetic Resonance Imaging of the Breast in the Preoperative Setting: Results of 2 Prospective International Multicenter Phase III Studies. AB - OBJECTIVES: The aim of this study was to evaluate the diagnostic efficacy of gadobutrol enhanced preoperative breast magnetic resonance imaging (MRI) in 2 prospective studies. MATERIALS AND METHODS: Approval of ethics committees and informed consent from patients were obtained. Both Gadobutrol-Enhanced MR Mammography (GEMMA) trials followed a standardized protocol using 1.5 T scanners. After unenhanced scans, patients received 0.1 mmol/kg of gadobutrol for the dynamic study. Six independent blinded readers, 3 for GEMMA1 and 3 for GEMMA2, assessed unenhanced images and, 2 or more weeks apart, contrast-enhanced plus unenhanced breast MRI images (CE-BMRI), using a standard 5-region scheme. Another 6 independent readers (3 for each study) evaluated mammograms alone. Sensitivity was calculated taking into account the identification of regions harboring malignancies (within-patient sensitivity), whereas specificity was based on cancer-free breasts. The first patient from each center was used for site qualification and blinded reader training and excluded from the efficacy analyses. Reference standard was pathology for regions harboring malignancy and a combination of negative pathology, mammography, and ultrasound for cancer-free regions. RESULTS: Of 906 breast cancer patients enrolled in 13 countries in the 2 studies, 865 received gadobutrol and 787 were evaluated for diagnostic performance (390 in GEMMA1 and 397 in GEMMA2). Within-patient sensitivity, that is, the detection rate of malignant disease extent per patient, ranged from 80% to 89% for CE-BMRI and was significantly superior to unenhanced breast MRI alone (37%-73%) and to mammography alone (68%-73%) for all readers in both trials. Specifity of the CE-BMRI ranged from 83% to 95%. CONCLUSION: In a very large multicenter preoperative setting, gadobutrol-enhanced breast MRI demonstrated high levels of sensitivity and specificity, consistent with published data on breast MRI. PMID- 26840496 TI - Access to and Interest in Using Smartphone Technology for the Management of Type 1 Diabetes in Ethnic Minority Adolescents and Their Parents. AB - BACKGROUND: A better understanding of parent and adolescent interest in using smartphone technology for type 1 diabetes (T1D) management is needed prior to developing technology-based interventions for ethnic minorities. This study examined access to and interest in technology-based programs for T1D in primarily Hispanic adolescents and their parents. SUBJECTS AND METHODS: During a scheduled clinic visit, adolescents with T1D (n = 50; 52% female; 13.6 +/- 2.0 years old; 74% Hispanic; hemoglobin A1c = 8.9 +/- 1.7%) and their parents (n = 49; 54% household income <$49,000) completed brief self-report surveys. RESULTS: Adolescents reported having access to the Internet (98%) and their own smartphones (86%). Thirty-seven percent reported using smartphone applications (apps) for their diabetes care, with 88% reporting carbohydrate counting as its primary function. Although most participants reported high/moderate interest in diabetes-specific apps, girls were more likely than boys to endorse high interest in apps to calculate and track insulin doses. A greater proportion of parents than of adolescents expressed high interest in apps to track glucose, count carbohydrates, calculate insulin doses, track insulin use, and receive diabetes related reminders. A greater proportion of parents than of adolescents also endorsed interest in a program that combined Internet use with smartphone apps. CONCLUSIONS: Results suggest ethnic minority adolescents with T1D across a range of income levels have access to smartphones. Although most parents expressed high interest in diabetes-specific apps, there was greater variability in adolescent interest. Understanding barriers and facilitators to the use of smartphone apps for diabetes care in ethnic minority adolescents may increase their interest in and ultimate adoption of this technology. PMID- 26840497 TI - Green Fluorescence of Cytaeis Hydroids Living in Association with Nassarius Gastropods in the Red Sea. AB - Green Fluorescent Proteins (GFPs) have been reported from a wide diversity of medusae, but only a few observations of green fluorescence have been reported for hydroid colonies. In this study, we report on fluorescence displayed by hydroid polyps of the genus Cytaeis Eschscholtz, 1829 (Hydrozoa: Anthoathecata: Filifera) found at night time in the southern Red Sea (Saudi Arabia) living on shells of the gastropod Nassarius margaritifer (Dunker, 1847) (Neogastropoda: Buccinoidea: Nassariidae). We examined the fluorescence of these polyps and compare with previously reported data. Intensive green fluorescence with a spectral peak at 518 nm was detected in the hypostome of the Cytaeis polyps, unlike in previous reports that reported fluorescence either in the basal parts of polyps or in other locations on hydroid colonies. These results suggest that fluorescence may be widespread not only in medusae, but also in polyps, and also suggests that the patterns of fluorescence localization can vary in closely related species. The fluorescence of polyps may be potentially useful for field identification of cryptic species and study of geographical distributions of such hydroids and their hosts. PMID- 26840498 TI - Moral fixations: The role of moral integrity and social anxiety in the selective avoidance of social threat. AB - People derive their sense of belonging from perceptions of being a moral person. Research moreover suggests that social cues of rejection rapidly influence visual scanning, and result in avoidant gaze behavior, especially in socially anxious individuals. With the current eye-tracking experiment, we therefore examined whether moral integrity threats and affirmations influence selective avoidance of social threat, and how this varies with individual differences in social anxiety. Fifty-nine participants retrieved a memory of a past immoral, moral, or neutral act. Next, participants passively viewed angry, happy, and neutral faces, while we recorded how often they first fixated on the eyes. In addition, we administered the Liebowitz Social Anxiety Scale (1987). Participants first fixated less on angry eyes compared to happy or neutral eyes when their moral integrity was threatened, and this selective avoidance was enhanced with increasing social anxiety. Following a moral affirmation, however, participants no longer selectively avoided the eyes of angry faces, regardless of individual differences in social anxiety. The results thus suggest that both low and high socially anxious people adjust their social gaze behavior in response to threats and affirmations of their moral integrity, pointing to the importance of the social context when considering affective processing biases. PMID- 26840499 TI - Estimates of the quality of complementary feeding among Vietnamese infants aged 6 23 months varied by how commercial baby cereals were classified in 24-h recalls. AB - The World Health Organization's (WHO) standardized questionnaire for assessing infant and young child feeding practices does not include commercial baby cereals (CBC), which are derived from several food groups and are fortified with micronutrients. We examined how different scenarios for classifying CBC affect estimates of the quality of complementary feeding in children ages 6-23 months in Vietnam in 2014 (n = 4811). In addition to the WHO standardized 24-h recall questionnaire for infant and young child feeding, we asked mothers about the consumption of CBC. The five resulting scenarios were S1 - omitted CBC; S2 - CBC classified as grains; S3 - as grains and dairy; S4 - as grains, dairy and fruit/vegetables; and S5 - as grains, dairy, fruit/vegetables and any others. Including CBC resulted in 4-11 percentage points higher in the prevalence of children who were fed each of the six food groups compared with what was reported in the WHO standardized questionnaire. Minimum dietary diversity (% fed >= 4 out of the 7 food groups) was higher in S5 (90%) than in S1 (84%), S2 (84%), S3 (85%) and S4 (86%). Minimum acceptable diet was also higher in scenarios S5 (80%) than in S1 (74%), S2 (75%), S3 (75%) and S4 (77%). Consumption of iron-rich foods was 94% when CBC was accounted, which was higher than the alternative scenario (89%). In summary, when CBC were included, population-level estimates of dietary quality were higher than when CBC were omitted. Guidance is required from the WHO about how to account for the consumption of CBC when estimating the quality of complementary feeding. PMID- 26840500 TI - Preventing Infections in Sickle Cell Disease: The Unfinished Business. AB - While encapsulated bacterial agents, particularly Streptococcus pneumoniae, are recognized as important microbes that are associated with serious illness in hosts with sickle cell disease (SCD), multiple pathogens are implicated in infectious manifestations of SCD. Variations in clinical practice have been an obstacle to the universal implementation of infection preventive management through active, targeted vaccination of these individuals and routine usage of antibiotic prophylaxis. Paradoxically, in low-income settings, there is evidence that SCD also increases the risk for several other infections that warrant additional infection preventive measures. The infection preventive care among patients with SCD in developed countries does not easily translate to the adoption of these recommendations globally, which must take into account the local epidemiology of infections, available vaccines and population-specific vaccine efficacy, environment, health care behaviors, and cultural beliefs, as these are all factors that play a complex role in the manifestation of SCD and the prevention of infectious disease morbidity. PMID- 26840501 TI - Zinc oxide nanorod assisted rapid single-step process for the conversion of electrospun poly(acrylonitrile) nanofibers to carbon nanofibers with a high graphitic content. AB - The effect of incorporation of rigid zinc oxide (ZnO) nanostructures on carbonization behavior of electrospun special acrylic fiber grade poly(acrylonitrile) (PAN-SAF) nanofibers was investigated. ZnO nanorods with high aspect ratios were incorporated into a PAN-N,N-dimethylformamide system and the composite nanofibers reinforced with aligned ZnO rods up to 50 wt% were successfully electrospun, and subsequently, carbonized. The morphology and the structural analysis of the resultant carbon nanofibers revealed that the rigid ZnO nanorods, present inside the nanofibers, possibly acted as scaffolds (temporary support structures) for immobilization of polymer chains and assisted in uniform heat distribution. This facilitated rapid and efficient conversion of the polymer structure to the ladder, and subsequently, the graphitized structure. At the end of the process, the ZnO nanorods were found to completely separate from the carbonized fibers yielding pure carbon nanofibers with a high graphitic content and surface area. The approach could be used to eliminate the slow, energy intensive stabilization step and achieve fast conversion of randomly laid carbon nanofiber webs in a single step to carbon nanofibers without the application of external tension or internal templates usually employed to achieve a high graphitic content in such systems. PMID- 26840502 TI - Less contribution of mast cells to the progression of renal fibrosis in Rat kidneys with chronic renal failure. AB - AIM: Chronic renal failure (CRF) is histopathologically characterized by tubulointerstitial fibrosis in addition to glomerulosclerosis. Although mast cells are known to infiltrate into the kidneys with chronic inflammation, we know little about their contribution to the pathogenesis of renal fibrosis associated with CRF. The aim of this study was to reveal the involvement of mast cells in the progression of renal fibrosis in CRF. METHODS: Using a rat model with CRF resulting from 5/6 nephrectomy, we examined the histopathological features of the kidneys and the infiltration of mast cells into the renal interstitium. By treating the rats with a potent mast cell stabilizer, tranilast, we also examined the involvement of mast cells in the progression of renal fibrosis associated with CRF. RESULTS: The CRF rat kidneys were characterized by the wide staining of collagen III and increased number of myofibroblasts, indicating the progression of renal fibrosis. Compared to T-lymphocytes or macrophages, the number of tryptase-positive mast cells was much smaller within the fibrotic kidneys and they did not proliferate in situ. The mRNA expression of mast cell-derived fibroblast-activating factors was not increased in the renal cortex isolated from CRF rat kidneys. Treatment with tranilast did not suppress the progression of renal fibrosis, nor did it ameliorate the progression of glomerulosclerosis and the interstitial proliferation of inflammatory leukocytes. CONCLUSIONS: This study demonstrated for the first time that mast cells are neither increased nor activated in the fibrotic kidneys of CRF rats. Compared to T-lymphocytes or macrophages that proliferate in situ within the fibrotic kidneys, mast cells were less likely to contribute to the progression of renal fibrosis associated with CRF. PMID- 26840504 TI - UV/H2O2 and UV/PDS Treatment of Trimethoprim and Sulfamethoxazole in Synthetic Human Urine: Transformation Products and Toxicity. AB - Elimination of pharmaceuticals in source-separated human urine is a promising approach to minimize the pharmaceuticals in the environment. Although the degradation kinetics of pharmaceuticals by UV/H2O2 and UV/peroxydisulfate (PDS) processes has been investigated in synthetic fresh and hydrolyzed urine, comprehensive evaluation of the advanced oxidation processes (AOPs), such as product identification and toxicity testing, has not yet been performed. This study identified the transformation products of two commonly used antibiotics, trimethoprim (TMP) and sulfamethoxazole (SMX), by UV/H2O2 and UV/PDS in synthetic urine matrices. The effects of reactive species, including *OH, SO4(*-), CO3(*-), and reactive nitrogen species, on product generation were investigated. Multiple isomeric transformation products of TMP and SMX were observed, especially in the reaction with hydroxyl radical. SO4(*-) and CO3(*-) reacted with pharmaceuticals by electron transfer, thus producing similar major products. The main reactive species deduced on the basis of product generation are in good agreement with kinetic simulation of the advanced oxidation processes. A strain identified as a polyphosphate-accumulating organism was used to investigate the antimicrobial activity of the pharmaceuticals and their products. No antimicrobial property was detected for the transformation products of either TMP or SMX. Acute toxicity employing luminescent bacterium Vibrio qinghaiensis indicated 20-40% higher inhibitory effect of TMP and SMX after treatment. Ecotoxicity was estimated by quantitative structure-activity relationship analysis using ECOSAR. PMID- 26840503 TI - DNA Origami: Folded DNA-Nanodevices That Can Direct and Interpret Cell Behavior. AB - DNA origami is a DNA-based nanotechnology that utilizes programmed combinations of short complementary oligonucleotides to fold a large single strand of DNA into precise 2D and 3D shapes. The exquisite nanoscale shape control of this inherently biocompatible material is combined with the potential to spatially address the origami structures with diverse cargoes including drugs, antibodies, nucleic acid sequences, small molecules, and inorganic particles. This programmable flexibility enables the fabrication of precise nanoscale devices that have already shown great potential for biomedical applications such as: drug delivery, biosensing, and synthetic nanopore formation. Here, the advances in the DNA-origami field since its inception several years ago are reviewed with a focus on how these DNA-nanodevices can be designed to interact with cells to direct or probe their behavior. PMID- 26840506 TI - Hollow Structured Micro/Nano MoS2 Spheres for High Electrocatalytic Activity Hydrogen Evolution Reaction. AB - Molybdenum disulfide (MoS2) has attracted extensive attention as a non-noble metal electrocatalyst for hydrogen evolution reaction (HER). Controlling the skeleton structure at the nanoscale is paramount to increase the number of active sites at the surface. However, hydrothermal synthesis favors the presence of the basal plane, limiting the efficiency of catalytic reaction. In this work, perfect hollow MoS2 microspheres capped by hollow MoS2 nanospheres (hH-MoS2) were obtained for the first time, which creates an opportunity for improving the HER electrocatalytic performance. Benefiting from the controllable hollow skeleton structure and large exposed edge sites, high-efficiency HER activity was obtained for stacked MoS2 thin shells with a mild degree of disorder, proving the presence of rich active sites and the validity of the combined structure. In general, the obtained hollow micro/nano MoS2 nanomaterial exhibits optimized electrocatalytic activity for HER with onset overpotential as low as 112 mV, low Tafel slope of 74 mV decade(-1), high current density of 10 mA cm(-2) at eta = 214 mV, and high TOF of 0.11 H2 s(-1) per active site at eta = 200 mV. PMID- 26840505 TI - Impact of xanthohumol (a prenylated flavonoid from hops) on DNA stability and other health-related biochemical parameters: Results of human intervention trials. AB - SCOPE: Xanthohumol (XN) is a hop flavonoid found in beers and refreshment drinks. Results of in vitro and animal studies indicate that it causes beneficial health effects due to DNA protective, anti-inflammatory, antioxidant, and phytoestrogenic properties. Aim of the present study was to find out if XN causes alterations of health-related parameters in humans. METHODS AND RESULTS: The effects of the flavonoid were investigated in a randomized crossover intervention trial (n = 22) in which the participants consumed a XN drink (12 mg XN/P/day). We monitored alterations of the DNA stability in single cell gel electrophoresis assays in lymphocytes and of several health-related biomarkers. A decrease of oxidatively damaged purines and protection toward reactive oxygen species induced DNA damage was found after the consumption of the beverage; also the excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-guanosine in urine was reduced. The assumption that the flavonoid causes DNA protection was confirmed in a randomized follow-up study with pure XN (n = 10) with a parallel design. Other biochemical parameters reflecting the redox- and hormonal status and lipid- and glucose metabolism were not altered after the intervention. CONCLUSION: Taken together, our data indicate that low doses of XN protect humans against oxidative DNA damage. PMID- 26840507 TI - Genetic background affects the expansion of macrophage subsets in the lungs of Mycobacterium tuberculosis-infected hosts. AB - M1 macrophages are more effective in the induction of the inflammatory response and clearance of Mycobacterium tuberculosis than M2 macrophages. Infected C57BL/6 mice generate a stronger cellular immune response compared with BALB/c mice. We hypothesized that infected C57BL/6 mice would exhibit a higher frequency and function of M1 macrophages than infected BALB/c mice. Our findings show a higher ratio of macrophages to M2 macrophages in the lungs of chronically infected C57BL/6 mice compared with BALB/c mice. However, there was no difference in the functional ability of M1 and M2 macrophages for the two strains in vitro. In vivo, a deleterious role for M2 macrophages was confirmed by M2 cell transfer, which rendered the infected C57BL/6, but not the BALB/c mice, more susceptible and resulted in mild lung inflammation compared with C57BL/6 mice that did not undergo cell transfer. M1 cell transfer induced a higher inflammatory response, although not protective, in infected BALB/c mice compared with their counterparts that did not undergo cell transfer. These findings demonstrate that an inflammation mediated by M1 macrophages may not induce bacterial tolerance because protection depends on the host genetic background, which drives the magnitude of the inflammatory response against M. tuberculosis in the pulmonary microenvironment. The contribution of our findings is that although M1 macrophage is an effector leucocyte with microbicidal machinery, its dominant role depends on the balance of M1 and M2 subsets, which is driven by the host genetic background. PMID- 26840508 TI - Impact of a Workplace Health Promotion Program on Employees' Blood Pressure in a Public University. AB - INTRODUCTION: Workplace health promotion is important in the prevention of non communicable diseases among employees. Previous workplace health programs have shown benefits such as lowered disease prevalence, reduced medical costs and improved productivity. This study aims to evaluate the impact of a 6-year workplace health promotion program on employees' blood pressure in a public university. METHODS: In this prospective cohort study, we included 1,365 employees enrolled in the university's workplace health promotion program, a program conducted since 2008 and using data from the 2008-2013 follow-up period. Participants were permanent employees aged 35 years and above, with at least one follow up measurements and no change in antihypertensive medication during the study period. Baseline socio-demographic information was collected using a questionnaire while anthropometry measurements and resting blood pressure were collected during annual health screening. Changes in blood pressure over time were analyzed using a linear mixed model. RESULTS: The systolic blood pressure in the hypertension subgroup decreased 2.36 mmHg per year (p<0.0001). There was also significant improvement in systolic blood pressure among the participants who were at risk of hypertension (-0.75 mmHg, p<0.001). The diastolic blood pressure among the hypertensive and at risk subgroups improved 1.76 mmHg/year (p<0.001) and 0.56 mmHg/year (p<0.001), respectively. However, there was no change in both systolic and diastolic blood pressure among participants in the healthy subgroup over the 6-year period. CONCLUSION: This study shows that continuing participation in workplace health promotion program has the potential to improve blood pressure levels among employees. PMID- 26840509 TI - Adult-onset Krabbe disease presenting with an isolated form of peripheral neuropathy. AB - INTRODUCTION: Adult-onset Krabbe disease is clinically rare and usually affects the pyramidal tracts in the central nervous system. Patients develop a spastic gait, and peripheral neuropathy sometimes occurs simultaneously. METHODS: A 55 year-old woman with consanguineous parents developed slowly progressive, asymmetric muscle weakness and atrophy in her forearms, while her ability to walk remained unaffected without pyramidal tract signs after onset at age 51 years. RESULTS: Nerve conduction studies demonstrated an asymmetric demyelinating-type peripheral neuropathy, and sural nerve biopsy documented reduced myelinated nerve fiber density with uniformly thin myelin sheaths, suggesting hypomyelination. Brain MRI demonstrated minor white-matter injury along the optic radiations, which was associated with asymptomatic, mild, prolonged latency on visual evoked potentials. Laboratory analysis documented low enzyme activity of galactocerebrosidase (GALC) and a known mutation of the GALC gene. CONCLUSION: Isolated peripheral neuropathy occurs very rarely in adult-onset Krabbe disease. Muscle Nerve 54: 152-157, 2016. PMID- 26840510 TI - Photoelectrochemistry of Pristine Mono- and Few-Layer MoS2. AB - Two-dimensional crystals are promising building blocks for the new generation of energy materials due to their low volume, high surface area, and high transparency. Electrochemical behavior of these crystals determines their performance in applications such as energy storage/conversion, sensing, and catalysis. Nevertheless, the electrochemistry of an isolated monolayer of molybdenum disulfide, which is one of the most promising semiconducting crystals, has not been achieved to date. We report here on photoelectrochemical properties of pristine monolayer and few-layer basal plane MoS2, namely the electron transfer kinetics and electric double-layer capacitance, supported by an extensive physical and chemical characterization. This enables a comparative qualitative correlation among the electrochemical data, MoS2 structure, and external illumination, although the absolute magnitudes of the electron transfer and capacitance are specific to the redox mediator and electrolyte used in these measurements ([Ru(NH3)6](3+/2+) and LiCl, respectively). Our work shows a strong dependence of the electrochemical properties on the number of MoS2 layers and illumination intensity and proves that an effective interlayer charge transport occurs in bulk MoS2. This highlights the exciting opportunities for tuning of the electrochemical performance of MoS2 through modification of its structure, external environment, and illumination. PMID- 26840511 TI - The use of a physiologically-based extraction test to assess relationships between bioaccessible metals in urban soil and neurodevelopmental conditions in children. AB - Intellectual disability (ID) and cerebral palsy (CP) are serious neurodevelopment conditions and low birth weight (LBW) is correlated with both ID and CP. The actual causes and mechanisms for each of these child outcomes are not well understood. In this study, the relationship between bioaccessible metal concentrations in urban soil and these child conditions were investigated. A physiologically based extraction test (PBET) mimicking gastric and intestinal processes was applied to measure the bio-accessibility of four metals (cadmium (Cd), chromium (Cr), nickel (Ni), and lead (Pb)) in urban soil, and a Bayesian Kriging method was used to estimate metal concentrations in geocoded maternal residential sites. The results showed that bioaccessible metal concentrations of Cd, Ni, and Pb in the intestinal phase were statistically significantly associated with the child outcomes. Lead and nickel were associated with ID, lead and cadmium was associated with LBW, and cadmium was associated with CP. The total concentrations and stomach concentrations were not correlated to significant effects in any of the analyses. For lead, an estimated threshold value was found that was statistically significant in predicting low birth weight. The change point test was statistically significant (p value = 0.045) at an intestine threshold level of 9.2 mg/kg (95% confidence interval 8.9-9.4, p value = 0.0016), which corresponds to 130.6 mg/kg of total Pb concentration in the soil. This is a narrow confidence interval for an important relationship. PMID- 26840512 TI - The developmental effect of difenoconazole on zebrafish embryos: A mechanism research. AB - Difenoconazole is a widely used triazole fungicide and has been reported to have negative impacts on zebrafish embryos. To investigate the mechanism of its developmental toxicity, zebrafish embryos were exposed to 0.5 and 2.0 mg/L difenoconazole for 96 h. The morphological and physiological indicators of embryo development were tested. The total cholesterol (TCHO) level, triglyceride (TG) level and malondialdehyde (MDA) content were measured at 96 hpf (hours post fertilization). In addition, the transcription of genes related to embryo development, the antioxidant system, lipid synthesis and metabolism was quantified. Our results showed that a large suite of symptoms were induced by difenoconazole, including hatching regression, heart rate decrease, growth inhibition and teratogenic effects. 0.5 mg/L difenoconazole could significantly increase the TG content of zebrafish embryos at 96 hpf, while no apparent change in the TCHO and MDA level was observed post 96 h exposure. Q-PCR (quantitative real-time polymerase chain reaction) results showed that the transcription of genes related to embryonic development was decreased after exposure. Genes related to hatching, retinoic acid metabolism and lipid homeostasis were up regulated by difenoconazole. PMID- 26840513 TI - The effect of silicon on iron plaque formation and arsenic accumulation in rice genotypes with different radial oxygen loss (ROL). AB - Rice is one of the major pathways of arsenic (As) exposure in human food chain, threatening over half of the global population. Greenhouse pot experiments were conducted to examine the effects of Si application on iron (Fe) plaque formation, As uptake and rice grain As speciation in indica and hybrid rice genotypes with different radial oxygen loss (ROL) ability. The results demonstrated that Si significantly increased root and grain biomass. Indica genotypes with higher ROL induced greater Fe plaque formation, compared to hybrid genotypes and sequestered more As in Fe plaque. Silicon applications significantly increased Fe concentrations in iron plaque of different genotypes, but it decreased As concentrations in the roots, straws and husks by 28-35%, 15-35% and 32-57% respectively. In addition, it significantly reduced DMA accumulation in rice grains but not inorganic As accumulation. Rice of indica genotypes with higher ROL accumulated lower concentrations of inorganic As in grains than hybrid genotypes with lower ROL. PMID- 26840514 TI - Monitoring and evaluation of antibiotic resistance genes in four municipal wastewater treatment plants in Harbin, Northeast China. AB - The development and proliferation of antibiotic resistance in pathogenic and environmental microorganisms is of great concern for public health. In this study, the distribution and removal efficiency of intI1 and eight subtypes of antibiotic resistance genes (ARGs) for tetracycline, sulfonamides, beta-lactams resistance in four municipal wastewater treatment plants (WWTPs) in Harbin, which locates in Songhua River basin in cold areas of China, were monitored by real time fluorescent quantitative PCR. The results showed that intI1 and 6 ARGs except for blaTEM and blaSHV were detected in wastewater and sludge samples and 0.3-2.7 orders of magnitude of ARGs removal efficiency in the four WWTPs were observed. The investigation on the removal of ARGs of different treatment units in one WWTP showed that the biological treatment unit played the most important role in ARGs removal (1.2-1.8 orders of magnitude), followed by UV disinfection, while primary physical treatment units can hardly remove any ARGs. Although all the WWTPs can remove ARGs effectively, ARGs concentrations are still relatively high in the effluent, their further attenuation should be investigated. PMID- 26840515 TI - Plant community and litter composition in temperate deciduous woodlots along two field gradients of soil Ni, Cu and Co concentrations. AB - Perennial plant communities in the proximity of metal smelters and refineries may receive substantial inputs of base metal particulate as well as sulphate from the co-emission of sulphur dioxide. The Ni refinery at Port Colborne (Canada) operated by Inco (now Vale Canada Ltd.) emitted Ni, Co and Cu, along with sulphur dioxide, between 1918 and 1984. The objectives were to determine if vascular plant community composition, including standing litter, in twenty-one woodlots on clay or organic soil, were related to soil Ni concentration which decreased in concentration with distance from the Ni refinery. The soil Ni concentration in the clay woodlots ranged from 16 to 4130 mg Ni/kg, and in the organic woodlots, ranged from 98 to 22,700 mg Ni/kg. The concentrations of Co and Cu in the soils were also elevated, and highly correlated with soil Ni concentration. In consequence, each series of woodlots constituted a 'fixed ratio ray' of metal mixture exposure. For each of the woodlots, there were 16 independent measurements of 'woodlot status' which were correlated with elevated soil Ni concentration. Of the 32 combinations, there were eight linear correlations with soil Ni concentration, considerably more than would be expected by chance alone at a p-value of 0.05. With the exception of mean crown rating for shrubs at the clay sites, the correlations were consistent with the hypothesis that increased soil metal concentrations would be correlated with decreased diversity, plant community health or fitness, and increased accumulation of litter. Only five of the eight linear correlations were from the organic woodlots, suggesting that the observations were not confounded with soil type nor range in soil metal concentrations. PMID- 26840516 TI - Assessing uncertainty in pollutant build-up and wash-off processes. AB - Assessing build-up and wash-off process uncertainty is important for accurate interpretation of model outcomes to facilitate informed decision making for developing effective stormwater pollution mitigation strategies. Uncertainty inherent to pollutant build-up and wash-off processes influences the variations in pollutant loads entrained in stormwater runoff from urban catchments. However, build-up and wash-off predictions from stormwater quality models do not adequately represent such variations due to poor characterisation of the variability of these processes in mathematical models. The changes to the mathematical form of current models with the incorporation of process variability, facilitates accounting for process uncertainty without significantly affecting the model prediction performance. Moreover, the investigation of uncertainty propagation from build-up to wash-off confirmed that uncertainty in build-up process significantly influences wash-off process uncertainty. Specifically, the behaviour of particles <150 MUm during build-up primarily influences uncertainty propagation, resulting in appreciable variations in the pollutant load and composition during a wash-off event. PMID- 26840517 TI - Elemental sulfur amendment decreases bio-available Cr-VI in soils impacted by leather tanneries. AB - This study investigated the potential use of elemental S (S(0)) to convert Cr-VI to Cr-III which should decrease the bio-availability hence, toxicity of Cr-VI in soils. The bio-available fraction of Cr in soil was measured by phosphate buffer extraction (PBE) and the results showed that the fraction is about 10% of the total Cr-VI and varied from 12.8 to 42.5 mg kg(-1). The addition of 4.0 mg g(-1) S(0) decreased PBE Cr-VI to <0.4 mg kg(-1) limit established for Cr-VI toxicity in soils. Synchrotron-based X-ray absorption near-edge structure (XANES), X-ray fluorescence (XRF) and micro-XRD revealed that Cr-III was the dominant species (99% of total Cr) and Cr was retained by hematite and goethite in soil. Fe containing minerals may have provided sufficient protection to render the dominant Cr-III species biochemically inert to redox processes in soils. It is concluded that S(0)amendment is a promising approach to remediate Cr-VI contaminated soils. PMID- 26840519 TI - Characterization of staphylococci in urban wastewater treatment plants in Spain, with detection of methicillin resistant Staphylococcus aureus ST398. AB - The objective of this study was to determine the prevalence of Staphylococcus in urban wastewater treatment plants (UWTP) of La Rioja (Spain), and to characterize de obtained isolates. 16 wastewater samples (8 influent, 8 effluent) of six UWTPs were seeded on mannitol-salt-agar and oxacillin-resistance-screening-agar-base for staphylococci and methicillin-resistant Staphylococcus aureus recovery. Antimicrobial susceptibility profile was determined for 16 antibiotics and the presence of 35 antimicrobial resistance genes and 14 virulence genes by PCR. S. aureus was typed by spa, agr, and multilocus-sequence-typing, and the presence of immune-evasion-genes cluster was analyzed. Staphylococcus spp. were detected in 13 of 16 tested wastewater samples (81%), although the number of CFU/mL decreased after treatment. 40 staphylococci were recovered (1-5/sample), and 8 of them were identified as S. aureus being typed as (number of strains): spa-t011/agr-II/ST398 (1), spa-t002/agr-II/ST5 (2), spa-t3262/agr-II/ST5 (1), spa-t605/agr-II/ST126 (3), and spa-t878/agr-III/ST2849 (1). S. aureus ST398 strain was methicillin resistant and showed a multidrug resistance phenotype. Virulence genes tst, etd, sea, sec, seg, sei, sem, sen, seo, and seu, were detected among S. aureus and only ST5 strains showed genes of immune evasion cluster. Thirty-two coagulase negative Staphylococcus of 12 different species were recovered (number of strains): Staphylococcus equorum (7), Staphylococcus vitulinus (4), Staphylococcus lentus (4), Staphylococcus sciuri (4), Staphylococcus fleurettii (2), Staphylococcus haemolyticus (2), Staphylococcus hominis (2), Staphylococcus saprophyticus (2), Staphylococcus succinus (2), Staphylococcus capitis (1), Staphylococcus cohnii (1), and Staphylococcus epidermidis (1). Five presented a multidrug resistance phenotype. The following resistance and virulence genes were found: mecA, lnu(A), vga(A), tet(K), erm(C), msr(A)/(B), mph(C), tst, and sem. We found that Staphylococcus spp. are normal contaminants of urban wastewater, including different lineages of S. aureus and a high diversity of coagulase negative species. The presence of multiple resistance and virulence genes, including mecA, in staphylococci of wastewater can be a concern for the public health. PMID- 26840518 TI - Birth outcome measures and prenatal exposure to 4-tert-octylphenol. AB - Exposure to 4-tert-octylphenol (tOP) has been linked with adverse health outcomes in animals and humans, while epidemiological studies about associations between prenatal exposure to tOP and fetal growth are extremely limited. We measured urinary tOP concentrations in 1100 pregnant women before their delivery, and examined whether tOP levels were associated with birth outcomes, including weight, length, head circumference and ponderal index at birth. tOP could be detected in all samples, and the median uncorrected and creatinine-corrected tOP concentrations were 0.90 MUg/L (range from 0.25 to 20.05 MUg/L) and 1.33 MUg/g creatinine (range from 0.15 to 42.49 MUg/g creatinine), respectively. Maternal urinary log-transformed tOP concentrations were significantly negatively associated with adjusted birth weight [beta (g) = -126; 95% confidence interval (CI): -197, -55], birth length [beta (cm) = -0.53; 95% CI:-0.93, -0.14], and head circumference [beta (cm) = -0.30; 95% CI: -0.54, -0.07], respectively. Additionally, considering sex difference, these significant negative associations were also found among male neonates, while only higher maternal tOP concentrations were associated with a significant decrease in birth weight among female neonates. This study suggested significant negative associations between maternal urinary tOP concentrations and neonatal sizes at birth, and they differed by neonatal sex. Further epidemiological studies are required to more fully elaborate the associations between prenatal tOP exposure and birth outcomes. PMID- 26840521 TI - Blood trihalomethane levels and the risk of total cancer mortality in US adults. AB - BACKGROUND: Although animal data have suggested the carcinogenic activity of trihalomethanes (THMs), there is inconsistent evidence supporting the link between THM exposure and cancers in humans. OBJECTIVES: We investigated the association between specific and total blood THM levels with the risk of total cancer mortality in adults. METHODS: We analyzed data from the 1999-2004 Third National Health and Nutrition Examination Survey and the Linked Mortality File of the United States. A total of 933 adults (20-59 years of age) with available blood THM levels and no missing data for other variables were included. Four different THM species (chloroform, bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform) were included, and the codes associated with cancer (malignant neoplasm) were C00 through C97, based on the underlying causes of death listed in the International Classification of Disease 10the Revision. RESULTS: Compared with adults in the lowest DBCM, bromoform, and total brominated THM tertiles, those in the highest DBCM, bromoform, and total brominated THM tertiles exhibited adjusted hazard ratios (HR) of total cancer mortality of 4.97 (95% confidence interval (CI) = 1.59-15.50), 4.94 (95% CI = 1.56-15.61), and 3.42 (95% CI = 1.21-15.43) respectively. The risk of total cancer mortality was not associated with increases in blood chloroform and total THM levels. CONCLUSIONS: We found that the baseline blood THM species, particularly brominated THMs, were significantly associated with total cancer mortality in adults. Although this study should be confirm by other studies, our findings suggest a possible link between THM exposures and cancer. PMID- 26840520 TI - Thallium transformation and partitioning during Pb-Zn smelting and environmental implications. AB - Thallium (Tl) is a toxic and non-essential heavy metal. Raw Pb-Zn ores and solid smelting wastes from a large Pb-Zn smelting plant - a typical thallium (Tl) pollution source in South China, were investigated in terms of Tl distribution and fractionation. A modified IRMM (Institute for Reference Materials and Measurement, Europe) sequential extraction scheme was applied on the samples, in order to uncover the geochemical behavior and transformation of Tl during Pb-Zn smelting and to assess the potential environmental risk of Tl arising from this plant. Results showed that the Pb-Zn ore materials were relatively enriched with Tl (15.1-87.7 mg kg(-1)), while even higher accumulation existed in the electrostatic dust (3280-4050 mg kg(-1)) and acidic waste (13,300 mg kg(-1)). A comparison of Tl concentration and fraction distribution in different samples clearly demonstrated the significant role of the ore roasting in Tl transformation and mobilization, probably as a result of alteration/decomposition of related minerals followed by Tl release and subsequent deposition/co precipitation on fine surface particles of the electrostatic dust and acidic waste. While only 10-30% of total Tl amounts was associated with the exchangeable/acid-extractable fraction of the Pb-Zn ore materials, up to 90% of total Tl was found in this fraction of the electrostatic dust and acidic waste. Taking into account the mobility and bioavailability of this fraction, these waste forms may pose significant environmental risk. PMID- 26840523 TI - Assessment of the biological and chemical availability of the freshly spiked and aged DDE in soil. AB - The study compared the ability of various chemical methods (XAD, beta hydroxypropylcyclodextrin - HPCD) and solid phase micro-extraction (SPME)) to mimic earthworm uptake from two similar soils containing either spiked or aged p,p'-DDE, thus representing two extreme scenarios with regard to the length of pollutant-soil contact time and the way of contamination. The extent of bioaccumulation was assessed at fixed exposure periods (10 and 21 days) and at equilibrium derived from uptake curves by multiple-point comparison or kinetic modeling. The decision on the best chemical predictor of biological uptake differed. The degree of bioaccumulation at equilibrium was best predicted by XAD while HPCD rather reflected the extent of accumulation derived after 21 days when, however, steady-state was not reached for spiked p,p'-DDE. SPME seemed to underestimate the uptake of aged p,p'-DDE, probably of the fraction taken up via soil particles. Thus, the degree of predictability seems to be associated with the capability of the chemical method to mimic the complex earthworm uptake via skin and intestinal tract as well as with the quality of biological data where the insufficient length of exposure period appears to be the major concern. PMID- 26840522 TI - Excessive apoptosis and defective autophagy contribute to developmental testicular toxicity induced by fluoride. AB - Fluoride, a ubiquitous environmental contaminant, is known to impair testicular functions and fertility; however the underlying mechanisms remain obscure. In this study, we used a rat model to mimic human exposure and sought to investigate the roles of apoptosis and autophagy in testicular toxicity of fluoride. Sprague Dawley rats were developmentally exposed to 25, 50, or 100 mg/L sodium fluoride (NaF) via drinking water from pre-pregnancy to post-puberty, and then the testes of offspring were excised on postnatal day 56. Our results demonstrated that developmental NaF exposure induced an enhanced testicular apoptosis, as manifested by a series of hallmarks such as caspase-3 activation, chromatin condensation and DNA fragmentation. Further study revealed that fluoride exposure elicited significant elevations in the levels of cell surface death receptor Fas with a parallel increase in cytoplasmic cytochrome c, indicating the involvement of both extrinsic and intrinsic apoptotic pathways. Intriguingly, fluoride treatment also simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II but not Beclin1. Unexpectedly, the expression of p62, a substrate that is degraded by autophagy, was also significantly elevated, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation rather than increased formation. Importantly, these were associated with marked histopathological lesions including spermatogenic failure and germ cell loss, along with severe ultrastructural abnormalities in testes. Taken together, our findings provide deeper insights into roles of excessive apoptosis and defective autophagy in the aggravation of testicular damage, which could contribute to a better understanding of fluoride-induced male reproductive toxicity. PMID- 26840524 TI - Physicochemical properties and ecotoxicological effects of yttrium oxide nanoparticles in aquatic media: Role of low molecular weight natural organic acids. AB - Understanding how engineered nanoparticles (ENPs) interact with natural organic acids is important to ecological risk assessment of ENPs, but this interaction remains poorly studied. Here, we investigate the dispersion stability, ion release, and toxicity of yttrium oxide nanoparticles (nY2O3) suspensions after exposure to two low molecular weight natural organic acids (LOAs), namely benzoic acid and gallic acid. We find that in the presence of LOAs the nY2O3 suspensions become more stable with surface zeta potential more positive or negative, accompanied by small agglomerated size. LOA interaction with nY2O3 is shown to promote the release of dissolved yttrium from the nanoparticles, depending on the concentrations of LOAs. Toxic effects of the nY2O3 suspensions incubated with LOAs on Scenedesmus obliquus as a function of their mixture levels show three types of signs: stimulation, inhibition, and alleviation. The mechanism of the effects of LOAs on the nY2O3 toxicity may be mainly associated with the degree of agglomeration, particle-induced oxidative stress, and dissolved yttrium. Our results stressed the importance of LOA impacts on the fate and toxicity of ENPs in the aquatic environment. PMID- 26840525 TI - Valuing the human health damage caused by the fraud of Volkswagen. AB - Recently it became known that Volkswagen Group has been cheating with emission tests for diesel engines over the last six years, resulting in on-road emissions vastly exceeding legal standards for nitrogen oxides in Europe and the United States. Here, we provide an estimate of the public health consequences caused by this fraud. From 2009 to 2015, approximately nine million fraudulent Volkswagen cars, as sold in Europe and the US, emitted a cumulative amount of 526 ktonnes of nitrogen oxides more than was legally allowed. These fraudulent emissions are associated with 45 thousand disability-adjusted life years (DALYs) and a value of life lost of at least 39 billion US dollars, which is approximately 5.3 times larger than the 7.3 billion US dollars that Volkswagen Group has set aside to cover worldwide costs related to the diesel emissions scandal. PMID- 26840526 TI - Gas and particle size distributions of polychlorinated naphthalenes in the atmosphere of Beijing, China. AB - Polychlorinated naphthalenes (PCNs) were listed as persistent organic pollutants in the Stockholm Convention in 2015. Despite numerous studies on PCNs, little is known about their occurrence in atmospheric particulate matter of different sizes. In this study, 49 PCN congeners were investigated for their concentrations and size-specific distributions in an urban atmosphere, and preliminary exposure assessments were conducted. Ambient air samples were collected using a high volume cascade impactor for division into a gas fraction and four particle size fractions. Samples were collected from October 2013 to June 2014 at an urban site in Beijing, China. The concentration range for PCNs in the atmosphere (gas + particle fractions) was 6.77-25.90 pg/m(3) (average 16.28 pg/m(3)). The particle bound concentration range was 0.17-2.78 pg/m(3) (average 1.73 pg/m(3)). Therefore, PCNs were mainly found in the gas phase. The concentrations of PCNs in a fraction increased as the particle size decreased (dae > 10 MUm, 10 MUm >= dae > 2.5 MUm, 2.5 MUm >= dae > 1.0 MUm and dae <= 1.0 MUm). Consequently, PCNs were ubiquitous in inhalable fine particles, and the SigmaPCNs associated with PM1.0 and PM2.5 reached 68.4% and 84.3%, respectively. Tetra-CNs and penta-CNs (the lower chlorinated homologues) predominated in the atmosphere. The homologue profiles in different size particles were almost similar, but the particulate profiles were different from those in the gas phase. Among the individual PCNs identified, CN38/40, CN52/60 and CN75 were the dominant compounds in the atmosphere. CN66/67 and CN73 collectively accounted for most of the total dioxin like TEQ concentrations of the PCNs. Exposure to toxic compounds, such as PCNs present in PM1.0 or PM2.5, may affect human health. This work presents the first data on size-specific distributions of PCNs in the atmosphere. PMID- 26840528 TI - Prevalence of upper gastrointestinal endoscopic findings in the community: A systematic review of studies in unselected samples of subjects. AB - BACKGROUND AND AIM: Upper gastrointestinal endoscopic findings, such as esophagitis, Barrett's esophagus, peptic ulcer, and malignancy, represent a public health problem. This systematic review aimed to evaluate the prevalence of upper gastrointestinal endoscopic findings in the community. METHODS: A systematic search was conducted in PUBMED and EMBASE to May 2015. Studies were eligible if they reported the prevalence of upper gastrointestinal endoscopic findings in unselected samples of the community. RESULTS: Twelve articles were eligible, nine reported data from three endoscopic surveys (n = 3063 subjects), and three from national screening programs (n = 84 153). The overall prevalence of upper gastrointestinal endoscopic findings in the community was 30% in the Kalixanda study (Sweden), 24.9% in the Loiano-Monghidoro study (Italy), and 68.9% in the Systematic Investigation of Gastrointestinal Diseases study (China). The pooled prevalence of esophagitis, endoscopically suspected esophageal metaplasia (ESEM), peptic ulcer, and gastric cancer in all studies was 11.2, 5.1, 6.8, and 0.33%, respectively. The most frequent finding was esophagitis in Europe, with a prevalence of 15.5% in Sweden and 11.8% in Italy, and peptic ulcer in China (17.1%), both in asymptomatic and symptomatic individuals. The prevalence of Helicobacter pylori was positively associated with the prevalence of peptic ulcer (r = 0.91) but negatively associated with the prevalence of both esophagitis (r = -0.99) and ESEM (r = -0.95). CONCLUSIONS: Upper gastrointestinal endoscopic findings are present in at least a quarter of subjects in the community with different patterns in Western and Eastern countries, both in asymptomatic and symptomatic subjects. H. pylori prevalence negatively impacts on the prevalence of reflux-related esophageal findings. PMID- 26840527 TI - Inward rectifier potassium (Kir2.1) channels as end-stage boosters of endothelium dependent vasodilators. AB - KEY POINTS: Increase in endothelial cell (EC) calcium activates calcium-sensitive intermediate and small conductance potassium (IK and SK) channels, thereby causing hyperpolarization and endothelium-dependent vasodilatation. Endothelial cells express inward rectifier potassium (Kir) channels, but their role in endothelium-dependent vasodilatation is not clear. In the mesenteric arteries, only ECs, but not smooth muscle cells, displayed Kir currents that were predominantly mediated by the Kir2.1 isoform. Endothelium-dependent vasodilatations in response to muscarinic receptor, TRPV4 (transient receptor potential vanilloid 4) channel and IK/SK channel agonists were highly attenuated by Kir channel inhibitors and by Kir2.1 channel knockdown. These results point to EC Kir channels as amplifiers of vasodilatation in response to increases in EC calcium and IK/SK channel activation and suggest that EC Kir channels could be targeted to treat endothelial dysfunction, which is a hallmark of vascular disorders. ABSTRACT: Endothelium-dependent vasodilators, such as acetylcholine, increase intracellular Ca(2+) through activation of transient receptor potential vanilloid 4 (TRPV4) channels in the plasma membrane and inositol trisphosphate receptors in the endoplasmic reticulum, leading to stimulation of Ca(2+) sensitive intermediate and small conductance K(+) (IK and SK, respectively) channels. Although strong inward rectifier K(+) (Kir) channels have been reported in the native endothelial cells (ECs) their role in EC-dependent vasodilatation is not clear. Here, we test the idea that Kir channels boost the EC-dependent vasodilatation of resistance-sized arteries. We show that ECs, but not smooth muscle cells, of small mesenteric arteries have Kir currents, which are substantially reduced in EC-specific Kir2.1 knockdown (EC-Kir2.1(-/-) ) mice. Elevation of extracellular K(+) to 14 mm caused vasodilatation of pressurized arteries, which was prevented by endothelial denudation and Kir channel inhibitors (Ba(2+) , ML-133) or in the arteries from EC-Kir2.1(-/-) mice. Potassium-induced dilatations were unaffected by inhibitors of TRPV4, IK and SK channels. The Kir channel blocker, Ba(2+) , did not affect currents through TRPV4, IK or SK channels. Endothelial cell-dependent vasodilatations in response to activation of muscarinic receptors, TRPV4 channels or IK/SK channels were reduced, but not eliminated, by Kir channel inhibitors or EC-Kir2.1(-/-) . In angiotensin II-induced hypertension, the Kir channel function was not altered, although the endothelium-dependent vasodilatation was severely impaired. Our results support the concept that EC Kir2 channels boost vasodilatory signals that are generated by Ca(2+) -dependent activation of IK and SK channels. PMID- 26840530 TI - Refining prognostication of thrombosis in ET. PMID- 26840529 TI - Oscillation, Conduction Delays, and Learning Cooperate to Establish Neural Competition in Recurrent Networks. AB - Specific memory might be stored in a subnetwork consisting of a small population of neurons. To select neurons involved in memory formation, neural competition might be essential. In this paper, we show that excitable neurons are competitive and organize into two assemblies in a recurrent network with spike timing dependent synaptic plasticity (STDP) and axonal conduction delays. Neural competition is established by the cooperation of spontaneously induced neural oscillation, axonal conduction delays, and STDP. We also suggest that the competition mechanism in this paper is one of the basic functions required to organize memory-storing subnetworks into fine-scale cortical networks. PMID- 26840531 TI - Dual-Functional Nanographene Oxide as Cancer-Targeted Drug-Delivery System to Selectively Induce Cancer-Cell Apoptosis. AB - Construction of bioresponsive drug-delivery nanosystems could enhance the anticancer efficacy of anticancer agents and reduce their toxic side effects. Herein, by using transferrin (Tf) as a surface decorator, we constructed a cancer targeted nanographene oxide (NGO) nanosystem for use in drug delivery. This nanosystem (Tf-NGO@HPIP) drastically enhanced the cellular uptake, retention, and anticancer efficacy of loaded drugs but showed much lower toxicity to normal cells. The nanosystem was internalized through receptor-mediated endocytosis and triggered pH-dependent drug release in acidic environments and in the presence of cellular enzymes. Moreover, Tf-NGO@HPIP effectively induced cancer-cell apoptosis through activation of superoxide-mediated p53 and MAPK pathways along with inactivation of ERK and AKT. Taken together, this study demonstrates a good strategy for the construction of bioresponsive NGO drug-delivery nanosystems and their use as efficient anticancer drug carriers. PMID- 26840532 TI - Music Attenuated a Decrease in Parasympathetic Nervous System Activity after Exercise. AB - Music and exercise can both affect autonomic nervous system activity. However, the effects of the combination of music and exercise on autonomic activity are poorly understood. Additionally, it remains unknown whether music affects post exercise orthostatic tolerance. The aim of this study was to evaluate the effects of music on autonomic nervous system activity in orthostatic tolerance after exercise. Twenty-six healthy graduate students participated in four sessions in a random order on four separate days: a sedentary session, a music session, a bicycling session, and a bicycling with music session. Participants were asked to listen to their favorite music and to exercise on a cycle ergometer. We evaluated autonomic nervous system activity before and after each session using frequency analysis of heart rate variability. High frequency power, an index of parasympathetic nervous system activity, was significantly increased in the music session. Heart rate was increased, and high frequency power was decreased, in the bicycling session. There was no significant difference in high frequency power before and after the bicycling with music session, although heart rate was significantly increased. Additionally, both music and exercise did not significantly affect heart rate, systolic blood pressure or also heart rate variability indices in the orthostatic test. These data suggest that music increased parasympathetic activity and attenuated the exercise-induced decrease in parasympathetic activity without altering the orthostatic tolerance after exercise. Therefore, music may be an effective approach for improving post exercise parasympathetic reactivation, resulting in a faster recovery and a reduction in cardiac stress after exercise. PMID- 26840533 TI - Yellow Mealworm Protein for Food Purposes - Extraction and Functional Properties. AB - A protocol for extraction of yellow mealworm larvae proteins was established, conditions were evaluated and the resulting protein extract was characterised. The freeze-dried yellow mealworm larvae contained around 33% fat, 51% crude protein and 43% true protein on a dry matter basis. The true protein content of the protein extract was about 75%, with an extraction rate of 70% under optimised extraction conditions using 0.25 M NaOH, a NaOH solution:ethanol defatted worm ratio of 15:1 mL/g, 40 degrees C for 1 h and extraction twice. The protein extract was a good source of essential amino acids. The lowest protein solubility in distilled water solution was found between pH 4 and 5, and increased with either increasing or decreasing pH. Lower solubility was observed in 0.5 M NaCl solution compared with distilled water. The rheological tests indicated that temperature, sample concentration, addition of salt and enzyme, incubation time and pH alterations influenced the elastic modulus of yellow mealworm protein extract (YMPE). These results demonstrate that the functional properties of YMPE can be modified for different food applications. PMID- 26840535 TI - The generation of human innate lymphoid cells is influenced by the source of hematopoietic stem cells and by the use of G-CSF. AB - NK cells play a central role in the haploidentical HSC transplantation (HSCT) to cure high-risk leukemias. Other innate lymphoid cells (ILCs) have been proposed to exert a protective role in graft-versus-host disease and could also contribute to anti-microbial defence and to lymphoid tissue remodeling. Thus, we investigated the ILC differentiation potential of HSCs isolated from BM, mobilized peripheral blood (PB), and umbilical cord blood (UCB). BM CD34(+) cells are enriched in lymphoid-committed precursors, while PB CD34(+) cells preferentially contain myeloid precursors. In vitro differentiation experiments revealed that the highest and the lowest CD56(+) CD161(+) ILC recovery was detected in UCB and PB HSC cultures, respectively. Among CD56(+) CD161(+) ILCs, the ratio between NK cells and ILC3s was similar for all HSC analyzed. ILC recovery in PB CD34(+) cultures was lower for G-CSF-mobilized HSCs (good mobilizers) than for G-CSF+plerixafor-mobilized HSC (poor mobilizers). Moreover, G-CSF inhibited in vitro ILC recovery and the degree of inhibition was proportional to the time of exposure to the cytokine. Thus, although all common sources of HSC for transplant differentiate towards ILCs, substantial differences exist among different sources and G-CSF may influence ILC recovery. These data offer new clues for a better understanding of the immune reconstitution after HSCT. PMID- 26840536 TI - Evaluation of growth hormone stimulation testing in children. AB - OBJECTIVE: To evaluate the use and interpretation of growth hormone (GH) stimulation tests used across the UK for diagnosing GH deficiency. BACKGROUND: Previous studies show poor consensus on the use of GH stimulation tests. Sex steroid priming and retesting in the transition period are areas not previously surveyed. DESIGN: Data were collected from tertiary paediatric endocrinologists, paediatricians with a specialist interest in endocrinology and biochemists across the UK over 6 months through distributing electronic surveys. RESULTS: At least three different GH stimulation tests were used by 33% of departments. Glucagon and insulin doses varied most, and sampling frequency varied most using insulin. All laboratories use a recommended chemiluminescence immunoassay with an acceptable coefficient of variability. The GH peak for diagnosing GH deficiency varied from 6 to 8 MUg/l. A wide range of clinical scenarios prompted retesting in the transition period, suggesting nonstandardized current practice. Seventy five per cent of departments use sex steroid priming, but follow criteria variously combining bone age, chronological age and pubertal stage, together with variations in steroid type and dose. CONCLUSIONS: Although a contentious diagnostic test, GH stimulation tests remain the gold standard for diagnosing GH deficiency. Our data suggest that together with variation in indication, protocol and interpretation, there is considerable variation in current practices pertaining to priming and retesting in transition. Given the current financial climate and the need for careful resource management, this study emphasizes the considerable need for consensus in the investigation, diagnosis and long-term follow-up of these children, at least nationally if not internationally. PMID- 26840534 TI - Fine-Tuning Covalent Inhibition of Bacterial Quorum Sensing. AB - Emerging antibiotic resistance among human pathogens has galvanized efforts to find alternative routes to combat bacterial virulence. One new approach entails interfering with the ability of bacteria to coordinate population-wide gene expression, or quorum sensing (QS), thus inhibiting the production of virulence factors and biofilm formation. We have recently developed such a strategy by targeting LasR, the master regulator of QS in the opportunistic human pathogen Pseudomonas aeruginosa, through the rational design of covalent inhibitors closely based on the core structure of the native ligand. We now report several groups of new inhibitors, one of which, fluoro-substituted ITC-12, displayed complete covalent modification of LasR, as well as effective QS inhibition in vitro and promising in vivo results. In addition to their potential clinical relevance, this series of synthetic QS modulators can be used as a tool to further unravel the complicated QS regulation in P. aeruginosa. PMID- 26840538 TI - Gestational weight gain and preterm birth in obese women: a systematic review and meta-analysis. AB - BACKGROUND: Prepregnant obesity is a global concern and gestational weight gain has been found to influence the risks of preterm birth. OBJECTIVE: To assess the relationship between gestational weight gain and risk for preterm birth in obese women. SEARCH STRATEGY: Four electronic databases were searched from 18 February through to 28 April 2015. SELECTION CRITERIA: Primary research reporting preterm birth as an outcome in obese women and gestational weight gain as a variable that could be compared to the 2009 Institute of Medicine's recommendations. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for inclusion. The Newcastle Ottawa Scale was used to assess study bias. MAIN RESULTS: Our search identified six studies meeting the inclusion criteria; five were conducted in the USA and one in Peru. Four studies with a total of 10 171 obese women were meta-analysed. Significant heterogeneity was found between studies in the pooled analysis. Results for indicated preterm birth in obese women with gestational weight gain above the Institute of Medicine's recommendations showed increased risk (adjusted odds ratio 1.54; 95% CI 1.09 2.16). CONCLUSIONS: Available science on this topic is limited to special populations of obese pregnant women. Generalisable research is needed to assess the variation in risk for preterm birth in obese women by differences in gestational weight gain and class of obesity controlling for significant variables in the pathway to preterm birth. This research has the potential to illuminate new science impacting preterm birth and interventions for prevention. PMID- 26840537 TI - The Role of T Cell Costimulation via DNAM-1 in Kidney Transplantation. AB - DNAX accessory protein-1 (DNAM-1, CD226) is a co-stimulatory and adhesion molecule expressed mainly by natural killer cells and T cells. DNAM-1 and its two ligands CD112 and CD155 are important in graft-versus-host disease, but their role in solid organ transplantation is largely unknown. We investigated the relevance of this pathway in a mouse kidney transplantation model. CD112 and CD155 are constitutively expressed on renal tubular cells and strongly upregulated in acutely rejected renal allografts. In vitro DNAM-1 blockade during allogeneic priming reduced the allospecific T cell response but not the allospecific cytotoxicity against renal tubular epithelial cells. Accordingly, absence of DNAM-1 in recipient mice or absence of CD112 or CD155 in the kidney allograft did not significantly influence renal function and severity of rejection after transplantation, but led to a higher incidence of infarcts in CD112 and CD155 deficient kidney allografts. Thus, DNAM-1 blockade is not effective in preventing transplant rejection. Despite of being highly expressed, CD112 and CD155 do not appear to play a major immunogenic role in kidney transplantation. Considering the high incidence of renal infarcts in CD112 and CD155 deficient grafts, blocking these molecules might be detrimental. PMID- 26840539 TI - Identification of Genes and Pathways Associated with Kidney Ischemia-Reperfusion Injury by Bioinformatics Analyses. AB - BACKGROUND/AIMS: Ischemia-reperfusion (IR) injury in the kidney is a major cause of acute kidney injury in humans. However, the molecular mechanisms responsible for the progression of kidney IR injury still need to be explored. In this study, we aimed to explore the underlying genes and pathways associated with kidney IR injury. METHODS: Gene microarray of GSE27274 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between kidney IR injury and kidney IR rat samples were analyzed. Gene Ontology biological process (BP) and pathway enrichment analyses of DEGs were performed, followed by protein-protein interaction (PPI) network construction. RESULTS: A total of 88 up-regulated and 102 down-regulated DEGs were identified. The up regulated DEGs including FK506 binding protein 1A (Fkb1a) were mainly enriched in biological processes (BPs) related to protein ubiquitination. The down-regulated DEGs including complement component 5 (C5) were enriched in complement and coagulation cascades pathway. Choline phosphotransferase 1 (Chpt1) was enriched in glycerophospholipid metabolism pathway. In the PPI network, heme oxygenase (decycling) 1 (Hmox1) was as a hub gene that interacted with the maximum nodes. CONCLUSIONS: DEGs of Fkb1a, C5, Chpt1, and Hmox1, as well as complement and coagulation cascades pathway, glycerophospholipid metabolism pathway, and BP terms related to protein ubiquitinatione may be the potential targets for diagnosis and treatment of kidney IR injury. PMID- 26840540 TI - Benzoate Allergy in Children--From Foods to Personal Hygiene Products. AB - Benzoate allergy may be an overlooked allergen in children and one that may be of increasing importance with its increasing role as a preservative in pediatric personal hygiene formulations. The cases herein report an association with cola and benzoate allergy and discusses the implications of replacement of formaldehyde by benzoates in personal hygiene products. PMID- 26840541 TI - First-Principles Simulations of One- and Two-Photon Absorption Band Shapes of the Bis(BF2) Core Complex. AB - Motivated by the outstanding properties of bis(BF2) core complexes as fluorophore probes, we present a systematic computational study of their vibrationally resolved one- and two-photon absorption spectra in vacuum and in solution. Electronic and vibrational structure calculations were performed using the coupled cluster CC2 method and the Kohn-Sham formulation of density functional theory (DFT). A nonempirical estimation of the inhomogeneous broadening, accomplished using the polarizable embedding (PE) approaches combined with time dependent DFT and CC2 methods, is used as a key ingredient of the computational protocol employed for simulations of the spectral features in solution. The inhomogeneous broadening is also determined based on the Marcus theory employing linear response and state-specific polarizable continuum model (PCM) methods. It is found that the polarizable embedding CC2 and the state-specific PCM are the most successful approaches for description of environmental broadening. For the 1(1)A(g) -> 1(1)B(u) transition, the non-Condon effects can be safely neglected and a fair agreement between the simulated and experimental band shapes is found. In contrast, the shape of the vibrationally resolved band corresponding to the two-photon allowed 1(1)A(g) -> 2(1)A(g) transition is largely dominated by non Condon effects. A generalized few-level model was also employed to analyze the mechanism of the electronic two-photon 1(1)A(g) -> 2(1)A(g) excitation. It was found that the most important optical channel involves the 1(1)B(u) excited state. Ramifications of the findings for general band shape modeling are briefly discussed. PMID- 26840542 TI - Time-invariant differences between plant individuals in interactions with arthropods correlate with intraspecific variation in plant phenology, morphology and floral scent. AB - The basic units of ecological and evolutionary processes are individuals. Network studies aiming to infer mechanisms from complex systems, however, usually focus on interactions between species, not individuals. Accordingly, the structure and underlying mechanisms of individual-based interaction networks remain largely unknown. In a common garden, we recorded all interactions on flowers and leaves of 97 Sinapis arvensis individuals from seedling stage to fruit set and related interindividual differences in interactions to the plant individuals' phenotypes. The plant individuals significantly differed in their quantitative and qualitative interactions with arthropods on flowers and leaves. These differences remained stable over the entire season and thus were time-invariant. Variation in interacting arthropod communities could be explained by a pronounced intraspecific variability in flowering phenology, morphology and flower scent, and translated into variation in reproductive success. Interestingly, plant individuals with a similar composition of flower visitors were also visited by a similar assemblage of interaction partners at leaves. Our results show that the nonuniformity of plant species has pronounced effects in community ecology, potentially with implications for the persistence of communities and populations, and their ability to withstand environmental fluctuations. PMID- 26840543 TI - Progressive Language Impairment in an English-Italian Bilingual Woman With Alzheimer Disease: An 18-Month Follow-up. PMID- 26840544 TI - The Relationship Between Mobility Dysfunction Staging and Global Cognitive Performance. AB - OBJECTIVES: To assess the relationship and the directionality between mobility and cognitive performance. METHOD: A cross-sectional analysis of a racially/ethnically diverse sample of 327 community-dwelling adults (mean age=68.9+/-9.9 y; range, 40 to 100 y) categorized as having no mobility dysfunction, upper-extremity (UE) impairment, lower-extremity (LE) impairment, or mobility limitation (both UE and LE impairments), and compared by global cognition with multiple hierarchical linear regression adjusted for sociodemographic, health, and mood factors. A bootstrapping mediation analysis investigated the directionality of the mobility-cognition association. RESULTS: LE (Est.=-2.95+/-0.77, P=0.001) but not UE impairment (Est.=-1.43+/-1.05, P=0.175) was associated with a poorer global cognitive performance/impairment. The presence of mobility limitation had the strongest effect on cognition (Est.= 3.78+/-1.09, P<0.001) adjusting for sociodemographic factors, body composition, comorbidities, and mood. Mediation analysis indicated that the relationship between cognition and mobility likely operates in both directions. DISCUSSION: The association between cognitive function and mobility follows a dose-response pattern in which the likelihood of poor global cognition increases with the progression of mobility dysfunction, with evidence that LE impairments may be better indicators of an impaired cognitive status than UE impairments. Using brief, valid tools to screen older patients for early signs of mobility dysfunction, especially when the LE is affected, is feasible, and may provide the first detectable stage of future cognitive impairment and provide actionable steps for interventions to improve performance, reduce burden, and prevent the development of physical disability and loss of independence. PMID- 26840545 TI - Default Mode Network Functional Connectivity in Early and Late Mild Cognitive Impairment: Results From the Alzheimer's Disease Neuroimaging Initiative. AB - BACKGROUND: Default mode network (DMN) functional connectivity is one of the neuroimaging candidate biomarkers of Alzheimer disease. However, no studies have investigated DMN connectivity at different stages of mild cognitive impairment (MCI). The aim of this study was to investigate patterns of DMN connectivity and its breakdown among cognitively normal (CN), early MCI (EMCI), and late MCI (LMCI) subjects. METHODS: Magnetic resonance imaging data and neuropsychological test scores from 130 subjects (CN=43, EMCI=47, LMCI=40) were obtained from the Alzheimer's Disease Neuroimaging Initiative. DMN functional connectivity was extracted using independent components analysis and compared between groups. RESULTS: Functional connectivity in the precuneus, bilateral medial frontal, parahippocampal, middle temporal, right superior temporal, and left angular gyri was decreased in EMCI subjects compared with CN subjects. When the 2 MCI groups were directly compared, LMCI subjects exhibited decreased functional connectivity in the precuneus, bilateral medial frontal gyri, and left angular gyrus. There was no significant difference in gray matter volume among the 3 groups. Amyloid positive EMCI subjects revealed more widespread breakdown of DMN connectivity than amyloid-negative EMCI subjects. A quantitative index of DMN connectivity correlated well with measures of cognitive performance. CONCLUSIONS: Our results suggest that the breakdown of DMN connectivity may occur in the early stage of MCI. PMID- 26840546 TI - Dementia and Cognitive Impairment Prevalence and Associated Factors in Indigenous Populations: A Systematic Review. AB - Population aging has been accompanied by worldwide growth in dementia. However, little is known about the prevalence of dementia and cognitive impairment not dementia in ethnically diverse populations, such as indigenous populations conceptualized as groups of persons who self-identify as indigenous and who are recognized as distinctive communities reproducing ancestral, historical, and territorial culture. This is particularly relevant in view of increasing life expectancy in indigenous populations and, consequently, in the number of elderly people, as well as the changes in their multimorbidity profile. In this study, a systematic review of the literature on the subject "cognitive impairment in indigenous elderly population" in the databases MEDLINE via PubMed, Lilacs, and Scopus showed that the prevalence of dementia in indigenous populations between 45 and 94 years old, originally from different countries, varied between 0.5% and 26.8% for age 60 and older, whereas the prevalence of cognitive impairment not dementia varied between 4.4% and 17.7%. Early onset of the disease, older age, low education level, and several poor health conditions were associated with prevalence rates and conversion from normal to any cognitive impairment. Cultural inadequacy of neuropsychological tests was the main factor reported in the selected studies, which makes the investigation of dementia a challenge in indigenous populations. These data reveal that the prevalence rates of dementia ranged from low to very high for those aged 60 years and older, with early onset of the disease and elevated mortality rate after initial diagnosis compared with the current global prevalence studies, suggesting that these individuals may be more vulnerable to cognitive disorders. Cognitive reserve and exposure to poor health status throughout life span may be considered in the interpretation of results. PMID- 26840549 TI - Photobiomodulation in Wound Healing: What Are We Not Considering? PMID- 26840547 TI - Are open-Label Placebos Ethical? Informed Consent and Ethical Equivocations. AB - The doctor-patient relationship is built on an implicit covenant of trust, yet it was not until the post-World War Two era that respect for patient autonomy emerged as an article of mainstream medical ethics. Unlike their medical forebears, physicians today are expected to furnish patients with adequate information about diagnoses, prognoses and treatments. Against these dicta there has been ongoing debate over whether placebos pose a threat to patient autonomy. A key premise underlying medical ethics discussion is the notion that the placebo effect necessitates patient deception. Indeed, the American Medical Association guidelines imply that placebo treatment necessary entails a form of deception. As a consequence of this assumption, the fulcrum of debate on the use of placebo treatment has hinged on whether that deception is ever justified. Recently performed experiments with open-label transparently prescribed placebos have begun to challenge the notion that deception is necessary in eliciting the placebo effect and such effects necessarily involve a binary distinction between autonomy and beneficence. In this article we focus on the content of disclosures in distinctive open-label, transparently disclosed placebo studies and inquire whether they might be said to invoke deception in clinical contexts, and if so, whether the deception is unethical. We find that open placebos may be said to involve equivocation over how placebos work. However, drawing on surveys of patient attitudes we suggest that this equivocation appears to be acceptable to patients. We conclude that open placebos fulfil current American Medical Association guidelines for placebo use, and propose future research directions for harnessing the placebo effect ethically. PMID- 26840550 TI - Removal of Dental Implants Using the Erbium,Chromium:Yttrium-Scandium-Gallium Garnet Laser and the Conventional Trephine Bur: An in Vitro Comparative Study. AB - OBJECTIVE: The purpose of this study was to compare the conventional trephine bur and the Erbium,chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser in removing implants in terms of the volume of removed bone, duration of the procedure, and morphological changes on the bone surface. MATERIALS AND METHODS: Three human mandibles were utilized, and four implants were inserted in each mandible using a drilling handpiece and burs. The implants were divided into two groups (n = 6) in which two implants from each mandible were removed using a trephine bur running at 1200 rounds per minute (rpm) with water irrigation. The remaining implants (n = 6) were removed with Er,Cr:YSGG laser (power 6 W, frequency 20 Hz, pulse duration 50 MUs, water 60, air 30). The volume of bone loss was calculated by filling the holes with mercury and measuring its volume. The preparation time was measured with a digital stopwatch and the postoperative bone surfaces were examined under a scanning electron microscope (SEM). RESULTS: The laser group exhibited a smaller amount of bone loss than the trephine bur group, whereas the latter required a shorter time of preparation. SEM revealed empty trabecular spaces with no signs of carbonization and well-defined edges in the laser group, whereas the trephine group displayed a surface covered with a smear layer and microcracks. CONCLUSIONS: The Er,Cr:YSGG laser provides superior results over the trephine bur in terms of bone preservation, thermal damage, and cutting efficiency. PMID- 26840551 TI - The Effects of Different Fluences of 1064 nm Q-Switched Nd:YAG Laser on Skin Repair and Skin Barrier Dysfunction in Mice. AB - OBJECTIVE: The purpose of this study was to investigate the effects of different fluences of Q-switched 1064 nm Nd:YAG laser on skin repair and barrier, and clarify its mechanisms. BACKGROUND DATA: The Q-switched 1064 nm Nd:YAG laser is widely used for rejuvenation, which needs appropriate fluence data to optimize efficacy and minimize side effects, and for elucidation of action mechanism. MATERIALS AND METHODS: The dorsal skin of BABL/c mice was administered 0, 1, 1.5, and 2 J/cm2 energy level laser, twice a week for 4 weeks. Immediately, 7, 14, 21, and 28 days after last treatment, the skin elasticity, moisture content, and transepidermal water loss (TEWL) were measured; 7, 14, 21, and 28 days after last treatment, the hydroxyproline content, mRNA level of procollagen types I and III, protein level of keratin-10 (K-10), filaggrin, transforming growth factor beta receptor II (TGFbetaRII), Smad2, and p65 were detected. RESULTS: Compared with the unirradiated control, the laser treatments decreased skin elasticity immediately, but increased skin moisture content in the 2 J/cm2 group, and then from day 21 to day 28, the skin elasticity, moisture content, hydroxyproline content, and gene expression of types I and III procollagen increased significantly. The TEWL value of the irradiated group significantly increased after irradiation immediately and 7 days after, K-10 and filaggrin were also decreased at 7 days after. The phosphorylation of TGFbetaRII (p-TGFbetaRII) increased at days 7 and 21, and phosphorylation of Smad2 (p-Smad2) was induced at 21 days. CONCLUSIONS: Irradiation of 1064 nm Q-switched Nd:YAG laser was able to markedly promote repair of mouse skin within 28 days through stimulation of collagen synthesis, with less skin barrier dysfunction, especially at the 1.5 J/cm2 fluence, and the activation of TGFbeta1-signaling pathways seemed to play an important role in repair. PMID- 26840553 TI - Physiological oxygen tension modulates soluble growth factor profile after crosstalk between chondrocytes and osteoblasts. AB - OBJECTIVES: Physiological oxygen tension plays a critical role in homoeostatic maintenance and development of endochondral bone. Based on the proximity between uncalcified cartilage and subchondral bone, and microchannels that serve as a message delivery network between them, we aimed to explore the influence of low oxygen tension on soluble factor secretion in both chondrocytes and osteoblasts, after co-culture. MATERIALS AND METHODS: Contact co-culture was achieved for morphological observation using red fluorescent protein (RFP)-labelled chondrocytes and green fluorescent protein (GFP)-labelled osteoblasts, and non contact co-culture achieved by transwell chambers. This was used to screen genetic variation of growth factors in hypoxia, including respective phenotypic markers, factors involving hypoxia and angiogenesis relationships, bone morphogenetic family proteins, and other general factors. RESULTS: We observed a significant increase in chondrocyte size following co-culture, in both normoxia and hypoxia, but not of osteoblasts. Expression of Aggrecan in chondrocytes and alkaline phosphatase in osteoblasts was down-regulated under hypoxia following co culture. Under hypoxia, we found that expression of hypoxia-inducible factor 1alpha, vascular endothelial growth factor-A/B, VE-cadherin, bone morphogenetic protein-2, and insulin-like growth factor-1 in chondrocytes, increased, but HIF 1alpha, platelet-derived growth factor, BMP-5/-6 and fibroblast growth factor-1 in osteoblasts, decreased. CONCLUSIONS: These results not only indicate the importance of crosstalk between chondrocytes and osteoblasts but also improve our understanding of the mechanisms underlying homoeostatic maintenance of endochondral bone. PMID- 26840554 TI - Energetics and Predissociation Dynamics of Small Water, HCl, and Mixed HCl-Water Clusters. AB - This Review summarizes recent research on vibrational predissociation (VP) of hydrogen-bonded clusters. Specifically, the focus is on breaking of hydrogen bonds following excitation of an intramolecular vibration of the cluster. VP of the water dimer and trimer, HCl clusters, and mixed HCl-water clusters are the major topics, but related work on hydrogen halide dimers and trimers, ammonia clusters, and mixed dimers with polyatomic units are reviewed for completion and comparison. The theoretical focus is on generating accurate potential energy surfaces (PESs) that can be used in detailed dynamical calculations, mainly using the quasiclassical trajectory approach. These PESs have to extend from the region describing large amplitude motion around the minimum to regions where fragments are formed. The experimental methodology exploits velocity map imaging to generate pair-correlated product translational energy distributions from which accurate bond dissociation energies of dimers and trimers and energy disposal in fragments are obtained. The excellent agreement between theory and experiment on bond dissociation energies, energy disposal in fragments, and the contributions of cooperativity demonstrates that it is now possible, with state-of-the-art experimental and theoretical methods, to make accurate predictions about dynamical and energetic properties of dissociating clusters. PMID- 26840555 TI - Nonmonotonic Elasticity of the Crude Oil-Brine Interface in Relation to Improved Oil Recovery. AB - Injection of optimized chemistry water in enhanced oil recovery (EOR) has gained much interest in the past few years. Crude oil-water interfaces can have a viscoelastic character affected by the adsorption of amphiphilic molecules. The brine concentration as well as surfactants may strongly affect the fluid-fluid interfacial viscoelasticity. In this work we investigate interfacial viscoelasticity of two different oils in terms of brine concentration and a nonionic surfactant. We correlate these measurements with oil recovery in a glass etched flow microchannel. Interfacial viscoelasticity develops relatively fast in both oils, stabilizing at about 48 h. The interfaces are found to be more elastic than viscous. The interfacial elastic (G') and viscous (G") moduli increase as the salt concentration decreases until a maximum in viscoelasticity is observed around 0.01 wt % of salt. Monovalent (Na(+)) and divalent (Mg(2+)) cations are used to investigate the effect of ion type; no difference is observed at low salinity. The introduction of a small amount of a surfactant (100 ppm) increases the elasticity of the crude oil-water interface at high salt concentration. Aqueous solutions that give the maximum interface viscoelasticity and high salinity brines are used to displace oil in a glass-etched "porous media" micromodel. Pressure fluctuations after breakthrough are observed in systems with high salt concentration while at low salt concentration there are no appreciable pressure fluctuations. Oil recovery increases by 5-10% in low salinity brines. By using a small amount of a nonionic surfactant with high salinity brine, oil recovery is enhanced 10% with no pressure fluctuations. Interface elasticity reduces the snap-off of the oil phase, leading to reduced pressure fluctuations. This study sheds light on significance of interface viscoelasticity in oil recovery by change in salt concentration and by addition of a small amount of a nonionic surfactant. PMID- 26840558 TI - Pyogenic Sacroiliitis in a 13-Month-Old Child: A Case Report and Literature Review: Erratum. PMID- 26840557 TI - Genomewide introgressive hybridization patterns in wild Atlantic salmon influenced by inadvertent gene flow from hatchery releases. AB - Many salmonid fish populations are threatened by genetic homogenization, primarily due to introgressive hybridization with hatchery-reared conspecifics. By applying genomewide analysis using two molecular marker types (1986 SNPs and 17 microsatellites), we assessed the genetic impacts of inadvertent gene flow via straying from hatchery releases on wild populations of Atlantic salmon in the Gulf of Finland, Baltic Sea, over 16 years (1996-2012). Both microsatellites and SNPs revealed congruent population genetic structuring, indicating that introgression changed the genetic make-up of wild populations by increasing genetic diversity and reducing genetic divergence. However, the degree of genetic introgression varied among studied populations, being higher in the eastern part and lower in the western part of Estonia, which most likely reflects the history of past stocking activities. Using kernel smoothing and permutation testing, we detected considerable heterogeneity in introgression patterns across the genome, with a large number of regions exhibiting nonrandom introgression widely dispersed across the genome. We also observed substantial variation in nonrandom introgression patterns within populations, as the majority of genomic regions showing elevated or reduced introgression were not consistently detected among temporal samples. This suggests that recombination, selection and stochastic processes may contribute to complex nonrandom introgression patterns. Our results suggest that (i) some genomic regions in Atlantic salmon are more vulnerable to introgressive hybridization, while others show greater resistance to unidirectional gene flow; and (ii) the hybridization of previously separated populations leads to complex and dynamic nonrandom introgression patterns that most likely have functional consequences for indigenous populations. PMID- 26840556 TI - Implication of aortic calcification on persistent hypertension after laparoscopic adrenalectomy in patients with primary aldosteronism. AB - OBJECTIVES: To identify risk factors, including aortic calcification, for persistent hypertension in primary aldosteronism patients undergoing laparoscopic adrenalectomy. METHODS: Between October 2000 and October 2015, we carried out 101 consecutive laparoscopic adrenalectomies for unilateral primary aldosteronism. Of these, 95 cases with at least 1 year of postoperative follow up were included. These were divided into two study groups based on whether they had normal blood pressure without antihypertensive medications (resolved group) or still required medications (unresolved group) at 1 year after surgery. Variables included age, sex, body mass index, history of hypertension, dosage of antihypertensive medication score, presence of type 2 diabetes, subclinical Cushing syndrome, preoperative renal function, aldosteronoma resolution score and abdominal calcification index. Univariate and multivariate logistic regression analyses were used to assess independent risk factors for persistent hypertension 1 year after surgery. RESULTS: The complete resolution of hypertension without antihypertensive medication 1 year after adrenalectomy was 36 out of 95 (38%). The preoperative antihypertensive medication score, systolic blood pressure and abdominal calcification index were significantly higher, and the aldosteronoma resolution score were significantly lower in the unresolved group than in the resolved group. Using multivariate logistic regression analysis, independent risk factors significantly correlating with persistent hypertension 1 year after surgery were aldosteronoma resolution score and abdominal calcification index. CONCLUSIONS: Laparoscopic adrenalectomy for primary aldosteronism is effective in improving blood pressure and reducing the need for antihypertensive medications. Aldosteronoma resolution score and abdominal calcification index represent potential independent risk factors for persistent hypertension 1 year after surgery. PMID- 26840559 TI - Intrinsic Properties of Two Benzodithiophene-Based Donor--Acceptor Copolymers Used in Organic Solar Cells: A Quantum-Chemical Approach. AB - Conjugated donor-acceptor (D-A) copolymers show tremendous promise as active components in thin-film organic bulk heterojunction solar cells and transistors, as appropriate combinations of D-A units enable regulation of the intrinsic electronic and optical properties of the polymer. Here, the structural, electronic, and optical properties of two D-A copolymers that make use of thieno[3,4-c]pyrrole-4,6-dione as the acceptor and differ by their donor unit benzo[1,2-b:4,5-b']dithiophene (BDT) vs the ladder-type heptacyclic benzodi(cyclopentadithiophene)-are compared using density functional theory methods. Our calculations predict some general similarities, although the differences in the donor structures lead also to clear differences. The extended conjugation of the stiff ladder-type donor destabilizes both the highest occupied and lowest unoccupied molecular orbital energies of the ladder copolymer and results in smaller gap energies compared to its smaller counterpart. However, more significant charge transfer nature is predicted for the smaller BDT-based copolymer by natural transition orbitals than for the ladder copolymer. That is, the influence of the acceptor on the copolymer properties is "diluted" to some extent by the already extended conjugation of the ladder-type donor. Thus, the use of stronger acceptor units with the ladder-type donors would benefit the future design of new D-A copolymers. PMID- 26840560 TI - Macro-Process of Past Plant Subsistence from the Upper Paleolithic to Middle Neolithic in China: A Quantitative Analysis of Multi-Archaeobotanical Data. AB - Detailed studies of the long-term development of plant use strategies indicate that plant subsistence patterns have noticeably changed since the Upper Paleolithic, when humans underwent a transitional process from foraging to agriculture. This transition was best recorded in west Asia; however, information about how plant subsistence changed during this transition remains limited in China. This lack of information is mainly due to a limited availability of sufficiently large, quantified archaeobotanical datasets and a paucity of related synthetic analyses. Here, we present a compilation of extensive archaeobotanical data derived from interdisciplinary approaches, and use quantitative analysis methods to reconstruct past plant use from the Upper Paleolithic to Middle Neolithic in China. Our results show that intentional exploitation for certain targeted plants, particularly grass seeds, may be traced back to about 30,000 years ago during the Upper Paleolithic. Subsequently, the gathering of wild plants dominated the subsistence system; however, this practice gradually diminished in dominance until about 6~5 ka cal BP during the Middle Neolithic. At this point, farming based on the domestication of cereals became the major subsistence practice. Interestingly, differences in plant use strategies were detected between north and south China, with respect to (1) the proportion of certain plant taxa in assemblages, (2) the domestication rate of cereals, and (3) the type of plant subsistence practiced after the establishment of full farming. In conclusion, the transition from foraging to rice and millet agriculture in China was a slow and long-term process spanning 10s of 1000s of years, which may be analogous to the developmental paths of wheat and barley farming in west Asia. PMID- 26840561 TI - Antifibrotic effect of Centella asiatica Linn and asiatic acid on arecoline induced fibrosis in human buccal fibroblasts. AB - AIM: The aim of the present study was to investigate the in vitro antifibrogenic effects of Centella asiatica Linn (CA) and its bioactive triterpene aglycone asiatic acid (AA) on arecoline-induced fibrosis in primary human buccal fibroblasts (HBF). METHODS: An ethanolic extract of CA was prepared, and AA was purchased commercially. High-performance thin-layer chromatography (HPTLC) was performed to quantify AA in the CA extract; colorimetric assay (3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was performed to determine an half-maximal inhibitory concentration. HBF were cultured and stimulated with arecoline. The inhibitory effects of CA and AA at different concentrations were assessed using gene-expression studies on fibrosis-related markers: transforming growth factor-beta1, collagen 1 type 2, and collagen 3 type 1. The stimulatory effect of arecoline and the inhibitory effect of AA on fibroblast morphology and extracellular matrix were assessed qualitatively using Masson trichrome stain. RESULTS: The HPTLC analysis determined 1.2% AA per 100 g of CA extract. Arecoline produced a concentration-dependent increase in the fibrotic markers, treatment with CA significantly downregulated fibrotic markers at higher concentrations, and AA downregulated at lower concentrations. Arecoline altered fibroblast morphology and stained strongly positive for collagen, and AA treatment regained fibroblast morphology with faint collagen staining. CONCLUSION: CA and AA can be used as antifibrotic agents. PMID- 26840562 TI - Pulmonary Consolidations due to Secondary Syphilis with Positive Bronchial Washing Immunohistochemistry. PMID- 26840564 TI - Tristetraprolin suppresses the EMT through the down-regulation of Twist1 and Snail1 in cancer cells. AB - Inhibition of epithelial-mesenchymal transition (EMT)-inducing transcription factors Twist and Snail prevents tumor metastasis but enhances metastatic growth. Here, we report an unexpected role of a tumor suppressor tristetraprolin (TTP) in inhibiting Twist and Snail without enhancing cellular proliferation. TTP bound to the AU-rich element (ARE) within the mRNA 3'UTRs of Twist1 and Snail1, enhanced the decay of their mRNAs and inhibited the EMT of cancer cells. The ectopic expression of Twist1 or Snail1 without their 3'UTRs blocked the inhibitory effects of TTP on the EMT. We also observed that TTP overexpression suppressed the growth of cancer cells. Our data propose a new model whereby TTP down regulates Twist1 and Snail1 and inhibits both the EMT and the proliferation of cancer cells. PMID- 26840563 TI - Oxidation of heat shock protein 60 and protein disulfide isomerase activates ERK and migration of human hepatocellular carcinoma HepG2. AB - Hepatocyte growth factor (HGF) and its receptor c-Met were frequently deregulated in hepatocellular carcinoma (HCC). Signaling pathways activated by HGF-c-Met are promising targets for preventing HCC progression. HGF can induce the reactive oxygen species (ROS) signaling for cell adhesion, migration and invasion of tumors including HCC. On the other hand, extracellular signal-regulated kinases (ERK), member of mitogen activated kinase, can be activated by ROS for a lot of cellular processes. As expected, HGF-induced phosphorylation of ERK and progression of HCC cell HepG2 were suppressed by ROS scavengers. By N-(biotinoyl) N'-(iodoacetyl)-ethylenediamine (BIAM) labeling method, a lot of cysteine (-SH) containing proteins with M.W. 50-75 kD were decreased in HepG2 treated with HGF or two other ROS generators, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and phenazine methosulfate. These redox sensitive proteins were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry. Among them, two chaperones, heat shock protein 60 (HSP60) and protein disulfide isomerase (PDI), were found to be the most common redox sensitive proteins in responding to all three agonists. Affinity blot of BIAM-labeled, immunoprecipitated HSP60 and PDI verified that HGF can decrease the cysteine ( SH) containing HSP60 and PDI. On the other hand, HGF and TPA increased cysteinyl glutathione-containing HSP60, consistent with the decrease of cysteine (-SH) containing HSP60. Moreover, depletion of HSP60 and PDI or expression of dominant negative mutant of HSP60 with alteration of Cys, effectively prevented HGF induced ERK phosphorylation and HepG2 migration.In conclusion, the redox sensitive HSP60 and PDI are required for HGF-induced ROS signaling and potential targets for preventing HCC progressions. PMID- 26840566 TI - Overexpression of lipocalin 2 in human cervical cancer enhances tumor invasion. AB - Cervical carcinoma is the third-most common cause of cancer-related deaths in women worldwide. However, the molecular mechanisms underlying the metastasis of cervical cancer are still unclear. Oligonucleotide microarrays coupled with bioinformatics analysis show that cytoskeletal remodeling and epithelial-to- mesenchymal transition (EMT) are significant pathways in clinical specimens of cervical cancer. In accord with clinical observations demonstrating ectopic expression of lipocalin 2 (LCN2), an oncogenic protein associated with EMT, in malignant tumors, was significantly upregulated in cervical cancer and correlated with lymph node metastasis. Overexpression of LCN2 enhanced tumor cell migration and invasion both in vitro and in vivo. Conversely, knockdown or neutralization of LCN2 reduced tumor cell migration and invasion. LCN2-induced migration was stimulated by activation of the EMT-associated proteins, Snail, Twist, N cadherin, fibronectin, and MMP-9. Our findings collectively support a potential role of LCN2 in cancer cell invasion through the EMT pathway and suggest that LCN2 could be effectively utilized as a lymph node metastasis marker in cervical cancer. PMID- 26840565 TI - Tumor-infiltrating macrophages express interleukin-25 and predict a favorable prognosis in patients with gastric cancer after radical resection. AB - Interleukin-25 (IL-25) is a recently identified member of the proinflammatory IL 17 cytokine family; however, its role in human tumors remains largely unknown. The aim of this study was to investigate the cellular source and clinical significance of IL-25 in gastric cancer (GC) in situ. The results demonstrated that macrophages (Mphis) were the primary IL-25-expressing cells (IL-25+) in GC in situ. Moreover, IL-25+ cells were highly enriched in the intra-tumoral (IT) region of GC tissues (p < 0.001). The production of IL-25 in Mphis exposed to culture supernatant from gastric cancer cell line SGC7901 in vitro was induced by transforming growth factor-beta1, and their density in the IT region was positively associated with those of other effector immune cells, namely, CD4+ T cells, CD8+ T cells and CD103+T cells (p < 0.01). This suggested that macrophages might produce IL-25 to create an antitumor micromilieu in GC tissues. The level of IL-25+IT cells was positively associated with histological grade (p < 0.001) and found to be an independent predictor of favorable survival (p = 0.024) in patients with GC after radical resection. These findings suggest that IL-25+IT cells may be a novel therapeutic target in those patients. PMID- 26840567 TI - Bevacizumab specifically decreases elevated levels of circulating KIT+CD11b+ cells and IL-10 in metastatic breast cancer patients. AB - BACKGROUND: Whether bevacizumab exerts its anti-tumor properties through systemic effects beyond local inhibition of angiogenesis and how these effects can be monitored in patients, remain largely elusive. To address these questions, we investigated bone marrow-derived cells and cytokines in the peripheral blood of metastatic breast cancer patients undergoing therapy with bevacizumab. METHODS: Circulating endothelial cells (CEC), circulating endothelial progenitor (CEP) and circulating CD11b+ cells in metastatic breast cancer patients before and during therapy with paclitaxel alone (n = 11) or in combination with bevacizumab (n = 10) were characterized using flow cytometry, real time PCR and RNASeq. Circulating factors were measured by ELISA. Aged-matched healthy donors were used as baseline controls (n = 12). RESULTS: Breast cancer patients had elevated frequencies of CEC, CEP, TIE2+CD11b+ and KIT+CD11b+ cell subsets. CEC decreased during therapy, irrespective of bevacizumab, while TIE2+CD11b+ remained unchanged. KIT+CD11b+ cells decreased in response to paclitaxel with bevacizumab, but not paclitaxel alone. Cancer patients expressed higher mRNA levels of the M2 polarization markers CD163, ARG1 and IL-10 in CD11b+ cells and increased levels of the M2 cytokines IL-10 and CCL20 in plasma. M1 activation markers and cytokines were low or equally expressed in cancer patients compared to healthy donors. Chemotherapy with paclitaxel and bevacizumab, but not with paclitaxel alone, significantly decreased IL-10 mRNA in CD11b+ cells and IL-10 protein in plasma. CONCLUSIONS: This pilot study provides evidence of systemic immunomodulatory effects of bevacizumab and identified circulating KIT+CD11b+ cells and IL-10 as candidate biomarkers of bevacizumab activity in metastatic breast cancer patients. PMID- 26840569 TI - Improving the understanding of Takotsubo syndrome: consequences of diagnosis and treatment. AB - Takotsubo syndrome was first described in Japan in 1990. Although it has gained worldwide recognition in the last 25 years, the pathophysiology of Takotsubo syndrome remains controversial. This syndrome is often reported in elderly postmenopausal women suffering from sudden, unexpected emotional and physical stress. Its clinical presentation resembles that of acute myocardial infarction. The prognosis of Takotsubo syndrome was initially considered favorable compared with that of myocardial infarction; however, subsequent studies have demonstrated that the mortality was higher than previously reported. Prompt diagnosis followed by appropriate management for acute complications such as heart failure, arrhythmia, intraventricular thrombus, and left ventricular outflow tract obstruction is required. We discuss the current knowledge on Takotsubo syndrome to facilitate optimal diagnosis and treatment. PMID- 26840568 TI - A systematic review of serum autoantibodies as biomarkers for pancreatic cancer detection. AB - Pancreatic cancer is a leading cause of cancer-related deaths in the western world. Patients with pancreatic cancer have poor prognosis, partly due to difficulties in detecting it at early stages. While different markers have been associated with pancreatic cancer, many of them show suboptimal sensitivity and specificity. Serum autoantibodies against tumor-associated antigens have recently emerged as early stage biomarkers for different types of cancers. Given the urgent need for early and reliable biomarkers for pancreatic cancer, we undertook a systematic review of the published literature to identify primary articles that evaluated serum autoantibodies in pancreatic cancer detection by searching PubMed and ISI Web of Knowledge. Two reviewers extracted data on study characteristics and results independently. Overall, 31 studies evaluating 124 individual serum autoantibodies in pancreatic cancer detection met the inclusion criteria. In general, single autoantibody markers showed relatively low sensitivities at high specificity. A combination of markers, either multiple serum autoantibodies or serum autoantibodies combined with tumor-associated markers, led to a better diagnostic performance. However, most of the analyzed autoantibodies have only been reported in single studies and therefore need to be independently validated. We conclude that serum autoantibodies might present an option as biomarkers for early detection of pancreatic cancer, but more work is needed to identify and validate autoantibody signatures that are associated with early stage pancreatic cancer. PMID- 26840595 TI - Diffuse Ventricular Fibrosis on Cardiac Magnetic Resonance Imaging Associates With Ventricular Tachycardia in Patients With Hypertrophic Cardiomyopathy. AB - INTRODUCTION: Non-sustained ventricular tachycardia (NSVT) is a risk factor for sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We aimed to assess whether diffuse ventricular fibrosis on cardiac magnetic resonance (CMR) imaging could be a surrogate marker for ventricular arrhythmias in patients with HCM. METHODS: A total of 100 patients with HCM (mean age 51 +/- 13 years, septal wall thickness 20 +/- 5 mm) underwent CMR with a 1.5 T scanner to determine the presence of ventricular late gadolinium enhancement (LGE) for focal fibrosis, and post-contrast T1 mapping for diffuse ventricular fibrosis. The presence of NSVT was determined by Holter monitoring and a subset of high risk patients received an implantable cardioverter-defibrillator (ICD). RESULTS: NSVT was detected in 23 of 100 patients with HCM. Focal ventricular fibrosis (by LGE) was observed in 87%, with no significant difference between patients with (96%) or without NSVT (86%, P = 0.19). However, LGE mass was greater in patients with (16.5 +/- 19.1 g) versus without NSVT (7.6 +/- 10.2 g, P < 0.01). NSVT was associated with a significant reduction in ventricular T1 relaxation time (422 +/ 54 milliseconds) versus patients without NSVT (512 +/- 115 milliseconds; P < 0.001). There was significant reduction in ventricular T1 relaxation time in patients with (430 +/- 48 milliseconds) versus without aborted SCD (495 +/- 113 milliseconds; P = 0.01) over a mean follow-up of 40 +/- 10 months. On multivariate analysis post-contrast ventricular T1 relaxation time and septal wall thickness were the only predictors of NSVT. CONCLUSION: Post-contrast T1 relaxation time on CMR is associated with ventricular arrhythmias in patients with HCM. Diffuse ventricular fibrosis may be an important marker of arrhythmic risk in patients with HCM. PMID- 26840570 TI - Public health clinic-based hepatitis C testing and linkage to care in Baltimore. AB - Testing and linkage to care are important determinants of hepatitis C virus (HCV) treatment effectiveness. Public health clinics serve populations at high risk of HCV. We investigated their potential to serve as sites for HCV testing, initiation of and linkage to HCV care. Cross-sectional study of patients accessing sexually transmitted infection (STI) care at the Baltimore City Health Department (BCHD) STI clinics, from June 2013 through April 2014 was conducted. Logistic regression was used to assess factors associated with HCV infection and specialist linkage to care. Between 24 June 2013 and 15 April 2014, 2681 patients were screened for HCV infection. Overall, 189 (7%) were anti-HCV positive, of whom 185 (98%) received follow-up HCV RNA testing, with 155 (84%) testing RNA positive. Of 155 RNA-positive individuals, 138 (89%) returned to the STI clinic for HCV RNA results and initial HCV care including counselling regarding transmission and harm reduction in alcohol, and 132 (85%) were referred to a specialist for HCV care. With provision of patient navigation services, 81 (52%) attended an offsite HCV specialist appointment. Alcohol use and lack of insurance coverage were associated with lower rates of specialist linkage (OR 0.4 [95% CI 0.1-0.9] and OR 0.4 [95% CI 0.1-0.9], respectively). We identified a high prevalence of HCV infection in BCHD STI clinics. With availability of patient navigation services, a large proportion of HCV-infected patients linked to off site specialist care. PMID- 26840597 TI - Reply. PMID- 26840596 TI - Host-Parasite Interactions and Purifying Selection in a Microsporidian Parasite of Honey Bees. AB - To clarify the mechanisms of Nosema ceranae parasitism, we deep-sequenced both honey bee host and parasite mRNAs throughout a complete 6-day infection cycle. By time-series analysis, 1122 parasite genes were significantly differently expressed during the reproduction cycle, clustering into 4 expression patterns. We found reactive mitochondrial oxygen species modulator 1 of the host to be significantly down regulated during the entire infection period. Our data support the hypothesis that apoptosis of honey bee cells was suppressed during infection. We further analyzed genome-wide genetic diversity of this parasite by comparing samples collected from the same site in 2007 and 2013. The number of SNP positions per gene and the proportion of non-synonymous substitutions per gene were significantly reduced over this time period, suggesting purifying selection on the parasite genome and supporting the hypothesis that a subset of N. ceranae strains might be dominating infection. PMID- 26840598 TI - Searching for the Optimal Sampling Solution: Variation in Invertebrate Communities, Sample Condition and DNA Quality. AB - There is a great demand for standardising biodiversity assessments in order to allow optimal comparison across research groups. For invertebrates, pitfall or flight-interception traps are commonly used, but sampling solution differs widely between studies, which could influence the communities collected and affect sample processing (morphological or genetic). We assessed arthropod communities with flight-interception traps using three commonly used sampling solutions across two forest types and two vertical strata. We first considered the effect of sampling solution and its interaction with forest type, vertical stratum, and position of sampling jar at the trap on sample condition and community composition. We found that samples collected in copper sulphate were more mouldy and fragmented relative to other solutions which might impair morphological identification, but condition depended on forest type, trap type and the position of the jar. Community composition, based on order-level identification, did not differ across sampling solutions and only varied with forest type and vertical stratum. Species richness and species-level community composition, however, differed greatly among sampling solutions. Renner solution was highly attractant for beetles and repellent for true bugs. Secondly, we tested whether sampling solution affects subsequent molecular analyses and found that DNA barcoding success was species-specific. Samples from copper sulphate produced the fewest successful DNA sequences for genetic identification, and since DNA yield or quality was not particularly reduced in these samples additional interactions between the solution and DNA must also be occurring. Our results show that the choice of sampling solution should be an important consideration in biodiversity studies. Due to the potential bias towards or against certain species by Ethanol containing sampling solution we suggest ethylene glycol as a suitable sampling solution when genetic analysis tools are to be used and copper sulphate when focusing on morphological species identification and facing financial restrictions in biodiversity studies. PMID- 26840600 TI - Near-misses at the Port Moresby General Hospital: a descriptive study. AB - BACKGROUND: The World Health Organization (WHO) defines 'maternal near-miss' as 'a woman who nearly died but survived a complication that occurred during pregnancy, childbirth or within 42 days of termination of her pregnancy'. With declining rates of maternal mortality, near-miss analysis is being examined in both developed and developing country settings for the assessment of obstetric care. AIMS: Over a 15-month period, details of cases that could be classified as 'near-misses' were collected at Port Moresby General Hospital (PMGH), to assess the practicality of collecting such data routinely and determine near-miss rates for the hospital. MATERIALS AND METHODS: Information about all cases that fitted the WHO definition of 'near-miss' was collected prospectively. RESULTS: During the audit period, there were 13 338 live births at PMGH; 131 women presented with a life-threatening condition of whom 122 met WHO criteria for 'maternal near miss'; there were nine maternal deaths. The maternal mortality ratio was 67.5/100 000 live births, the maternal near-miss index ratio 9.1/1000 live births and the combination of maternal deaths and near-misses gave a severe maternal outcome ratio of 9.8/1000 live births. Main causes of the 'near-misses' were obstetric haemorrhage, hypertensive disorders and infections. Grandmultiparity, nulliparity, no antenatal attendance and age beyond 30 years were associated with maternal near-misses. CONCLUSION: Assessment of near-misses equivalent to that provided in developed countries is possible in less well-resourced settings such as PMGH. Knowledge of causes of near-misses will assist health professionals to anticipate or prevent devastating maternal morbidities and thereby improve maternal and perinatal outcomes. PMID- 26840599 TI - Systems Genetics Analysis of a Recombinant Inbred Mouse Cell Culture Panel Reveals Wnt Pathway Member Lrp6 as a Regulator of Adult Hippocampal Precursor Cell Proliferation. AB - In much animal research, genetic variation is rather avoided than used as a powerful tool to identify key regulatory genes in complex phenotypes. Adult hippocampal neurogenesis is one such highly complex polygenic trait, for which the understanding of the molecular basis is fragmented and incomplete, and for which novel genetic approaches are needed. In this study, we aimed at marrying the power of the BXD panel, a mouse genetic reference population, with the flexibility of a cell culture model of adult neural precursor proliferation and differentiation. We established adult-derived hippocampal precursor cell cultures from 20 strains of the BXD panel, including the parental strains C57BL/6J and DBA/2J. The rates of cell proliferation and neuronal differentiation were measured, and transcriptional profiles were obtained from proliferating cultures. Together with the published genotypes of all lines, these data allowed a novel systems genetics analysis combining quantitative trait locus analysis with transcript expression correlation at a cellular level to identify genes linked with the differences in proliferation. In a proof-of-principle analysis, we identified Lrp6, the gene encoding the coreceptor to Frizzled in the Wnt pathway, as a potential negative regulator of precursor proliferation. Overexpression and siRNA silencing confirmed the regulatory role of Lrp6. As well as adding to our knowledge of the pathway surrounding Wnt in adult hippocampal neurogenesis, this finding allows the new appreciation of a negative regulator within this system. In addition, the resource and associated methodology will allow the integration of regulatory mechanisms at a systems level. PMID- 26840602 TI - Antipsychotic Dose Mediates the Association between Polypharmacy and Corrected QT Interval. AB - Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a cross-sectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy. PMID- 26840601 TI - Therapeutic Efficacy of an omega-3-Fatty Acid-Containing 17-beta Estradiol Nano Delivery System against Experimental Atherosclerosis. AB - Atherosclerosis and its consequences remain prevalent clinical challenges throughout the world. Initiation and progression of atherosclerosis involves a complex, dynamic interplay among inflammation, hyperlipidemia, and endothelial dysfunction. A multicomponent treatment approach targeted for delivery within diseased vessels could prove beneficial in treating atherosclerosis. This study was undertaken to evaluate the multimodal effects of a novel omega-3-fatty acid rich, 17-beta-estradiol (17-betaE)-loaded, CREKA-peptide-modified nanoemulsion system on experimental atherosclerosis. In vitro treatment of cultured human aortic endothelial cells (ECs) with the 17-betaE-loaded, CREKA-peptide-modified nanoemulsion system increased cellular nitrate/nitrite, indicating improved nitric oxide formation. In vivo, systemic administration of this nanoemulsion system to apolipoprotein-E knock out (ApoE-/-) mice fed a high-fat diet significantly improved multiple parameters related to the etiology and development of occlusive atherosclerotic vasculopathy: lesion area, circulating plasma lipid levels, and expression of aortic-wall inflammatory markers. These salutary effects were attributed selectively to the 17-betaE and/or omega-3 polyunsaturated fatty acid components of the nano-delivery system. At therapeutic doses, the 17-betaE-loaded, CREKA-peptide modified nanoemulsion system appeared to be biocompatible in that it elicited no apparent adverse/toxic effects, as indexed by body weight, plasma alanine aminotransferase/aspartate aminotransferase levels, and liver and kidney histopathology. The study demonstrates the therapeutic potential of a novel, 17-betaE-loaded, CREKA-peptide modified nanoemulsion system against atherosclerosis in a multimodal fashion by reducing lesion size, lowering the levels of circulating plasma lipids and decreasing the gene expression of inflammatory markers associated with the disease. PMID- 26840603 TI - The Adaptation, Face, and Content Validation of a Needs Assessment Tool: Progressive Disease for People with Interstitial Lung Disease. AB - BACKGROUND: Irrreversible interstitial lung disease (ILD) is associated with high morbidity and mortality. Palliative care needs of patients and caregivers are not routinely assessed; there is no tool to identify needs and triage support in clinical practice. OBJECTIVE: The study objective was to adapt and face/content validate a palliative needs assessment tool for people with ILD. METHODS: The Needs Assessment Tool: Progressive Disease-Cancer (NAT:PD-C) was adapted to reflect the palliative care needs identified from the ILD literature and patient/caregiver interviews. Face and content validity of the NAT:PD-ILD was tested using patient/caregiver focus groups and an expert consensus group. Participants in the study were two English tertiary health care trusts' outpatients clinics. There were four focus groups: two patient (n = 7; n = 4); one caregiver (n = 3); and one clinician (n = 8). There was a single caregiver interview, and an expert consensus group-academics (n = 3), clinicians (n = 9), patients (n = 4), and caregivers (n = 2). Each item in the tool was revised as agreed by the groups. Expert consensus was reached. RESULTS: Overall, the tool reflected participants' experience of ILD. Each domain was considered relevant. Adaptations were needed to represent the burden of ILD: respiratory symptoms (especially cough) and concerns about sexual activity were highlighted. All emphasized assessment of caregiver need as critical, and the role of caregivers in clinical consultations. CONCLUSIONS: The NAT:PD-ILD appears to have face and content validity. The inclusion of the family caregiver in the consultation as someone with their own needs as well as a source of information was welcomed. Reliability testing and construct validation of the tool are ongoing. PMID- 26840604 TI - Unraveling the recertification conundrum. PMID- 26840605 TI - Physician assistant postgraduate education. PMID- 26840607 TI - Advances in total knee arthroplasty. AB - Total knee arthroplasty (TKA) is one of the success stories of modern surgery. Primary TKA is commonly used when nonsurgical treatments for osteoarthritis fail. The need for TKA is projected to increase by 673% between 2005 and 2030, creating a tremendous burden on the healthcare system. This article reviews selected perioperative management strategies, computer-aided navigation, patient-specific cutting blocks, and medial pivot knee implants as potential sources of improvements in clinical efficiency and patient outcomes. PMID- 26840606 TI - Abdominal aortic aneurysm: A ticking time bomb. AB - Abdominal aortic aneurysm (AAA) is a clinical challenge in risk assessment, recognition, treatment, and prevention. This article explores the pathogenesis, presentation, diagnosis, treatment, and prevention of AAA. PMID- 26840608 TI - Perceived efficacy and utility of postgraduate physician assistant training programs. AB - OBJECTIVE: The purpose of this study was to explore graduates' perceptions of the efficacy and perceived utility of postgraduate physician assistant (PA) programs. METHODS: Using an online tool, a survey was sent to postgraduate PA program graduates that contained demographic questions and descriptive questions examining the perceived utility of completing a postgraduate PA program. RESULTS: Surveys were e-mailed to 149 graduates of postgraduate PA programs; 113 responded (75% response rate). After completing postgraduate training, 97% of graduates felt their training made them more competitive in the job market; 74% believed time from orientation to full productivity was reduced; and 95% would recommend completion of a postgraduate training program. CONCLUSIONS: Completion of a postgraduate PA program is an alternative to on-the-job training. Graduates perceived that the benefits from these programs include increased competitiveness in the job market, decreased onboarding time, and overall enhancement of their professional careers. PMID- 26840609 TI - From the Editor-in-Chief of Endocrine Reviews on the Occasion of the 2016 Centennial of the Endocrine Society. PMID- 26840612 TI - Complexity matching effects in bimanual and interpersonal syncopated finger tapping. AB - The current study was designed to investigate complexity matching during syncopated behavioral coordination. Participants either tapped in (bimanual) syncopation using their two hands, or tapped in (interpersonal) syncopation with a partner, with each participant using one of their hands. The time series of inter-tap intervals (ITI) from each hand were submitted to fractal analysis, as well as to short-term and multi-timescale cross-correlation analyses. The results demonstrated that the fractal scaling of one hand's ITI was strongly correlated to that of the other hand, and this complexity matching effect was stronger in the bimanual condition than in the interpersonal condition. Moreover, the degree of complexity matching was predicted by the strength of short-term cross correlation and the stability of the asynchrony between the two tapping series. These results suggest that complexity matching is not specific to the inphase synchronization tasks used in past research, but is a general result of coordination between complex systems. PMID- 26840613 TI - Chemoenzymatic Total Syntheses of the Enantiomers of the Protoilludanes 8 Deoxydihydrotsugicoline and Radudiol. AB - Chemoenzymatic and stereoselective total syntheses of the non-natural enantiomeric forms of the recently isolated protoilludane natural products 8 deoxydihydrotsugicoline (1) and radudiol (2) (viz. ent-1 and ent-2, respectively) are reported. The key steps involve the Diels-Alder cycloaddition of cyclopent-2 en-1-one to the acetonide derived from enantiomerically pure and enzymatically derived cis-1,2-dihydrocatechol 3, elaboration of the resulting adduct to the tricyclic ketone 12, and a photochemically promoted rearrangement of this last compound to the octahydro-1H-cyclobuta[e]indenone 13. PMID- 26840614 TI - Hygiene Behaviors Associated with Influenza-Like Illness among Adults in Beijing, China: A Large, Population-Based Survey. AB - The objective of this study was to identify possible hygiene behaviors associated with the incidence of ILI among adults in Beijing. In January 2011, we conducted a multi-stage sampling, cross-sectional survey of adults living in Beijing using self-administered anonymous questionnaires. The main outcome variable was self reported ILI within the past year. Multivariate logistic regression was used to identify factors associated with self-reported ILI. A total of 13003 participants completed the questionnaires. 6068 (46.7%) of all participants reported ILI during the past year. After adjusting for demographic characteristics, the variables significantly associated with a lower likelihood of reporting ILI were regular physical exercise (OR 0.80; 95% CI 0.74-0.87), optimal hand hygiene (OR 0.87; 95% CI 0.80-0.94), face mask use when going to hospitals (OR 0.87; 95% CI 0.80-0.95), and not sharing of towels and handkerchiefs (OR 0.68; 95% CI 0.63 0.73). These results highlight that personal hygiene behaviors were potential preventive factors against the incidence of ILI among adults in Beijing, and future interventions to improve personal hygiene behaviors are needed in Beijing. PMID- 26840615 TI - Understanding drivers of Demand for Emergency Service Trends in Years 2010-2014 in New South Wales: An initial overview of the DESTINY project. AB - OBJECTIVE: This study aims to describe the general characteristics and data definitions used in a population-based data set of ED presentations in New South Wales (NSW), used to form the basis of future-trend analyses. METHODS: Retrospective analysis of the Emergency Department Data Collection registry, which provided clinical and demographic information of ED presentations across all EDs in NSW between 2010 and 2014. Presenting problems and ED diagnoses were classified using broad clinical categories including injury/musculoskeletal, respiratory, cardiovascular, ear nose and throat, and mental health. Presentations were linked by patient to allow for analysis of representations, and population data were obtained from the Australian Bureau of Statistics. RESULTS: There were 11.8 million presentations that were analysed from 150 EDs (80.6% of all EDs). The rate of ED presentations was highest in those aged 85 years and older and appears to increase across all age groups between 2010 and 2014. The most common ED diagnosis categories were injury/musculoskeletal (27.5%) followed by abdominal/gastrointestinal (12.3%), respiratory (9%) and cardiovascular (8%). Both the Systematised Nomenclature of Medicine Clinical Terms (66%) and the International Classification of Diseases (24%) were used to code ED diagnoses. CONCLUSIONS: The elderly population had the highest rate of ED attendances. The use of diverse diagnosis classifications and source information systems may present problems with further analysis. Patterns and characteristics of ED presentations in NSW were broadly consistent with those reported in other states in Australia. PMID- 26840616 TI - Long-Term Extracorporeal Membrane Oxygenation as Bridging Strategies to Lung Transplantation in Rapidly Devastating Isolated Langerhans Cell Histiocytosis. AB - Isolated pulmonary involvement in pediatric Langerhans cell histiocytosis (LCH) is extremely rare. While the multisystem-LCH course varies from spontaneous remission to rapid deterioration with lethal outcome, single system involvement is generally associated with favorable prognosis. A child with isolated pulmonary LCH had an extremely rapid progression leading to respiratory failure, despite treatment with prednisone and vinblastine. Since lung hyperinflation and cystic degeneration contraindicated conventional mechanical ventilation, extracorporeal membrane oxygenation (ECMO) was chosen for 50 days as a bridge to lung transplantation. The mechanisms involved in disease progression and the usefulness of long-term ECMO are discussed. PMID- 26840617 TI - Multifunctional nanoparticle-protein conjugates with controllable bioactivity and pH responsiveness. AB - The modulation of protein activity is of significance for disease therapy, molecular diagnostics, and tissue engineering. Nanoparticles offer a new platform for the preparation of protein conjugates with improved protein properties. In the present work, Escherichia coli (E. coli) inorganic pyrophosphatase (PPase) and poly(methacrylic acid) (PMAA) were attached together to gold nanoparticles (AuNPs), forming AuNP-PPase-PMAA conjugates having controllable multi biofunctionalities and responsiveness to pH. By treating with poly(2 (dimethylamino)ethyl methacrylate) (PDMAEMA) and regulating the pH, the bioactivity of the conjugate becomes "on/off"-switchable. In addition, by taking advantage of the ability of AuNPs to undergo reversible aggregation/dispersion, the conjugates can be recycled and reused multiple times; and due to the shielding effect of the PMAA, the conjugated enzyme has high resistance to protease digestion. This approach has considerable potential in areas such as controlled delivery and release of drugs, biosensing, and biocatalysis. PMID- 26840618 TI - Delivering Nucleic-Acid Based Nanomedicines on Biomaterial Scaffolds for Orthopedic Tissue Repair: Challenges, Progress and Future Perspectives. AB - As well as acting to fill defects and allow for cell infiltration and proliferation in regenerative medicine, biomaterial scaffolds can also act as carriers for therapeutics, further enhancing their efficacy. Drug and protein delivery on scaffolds have shown potential, however, supraphysiological quantities of therapeutic are often released at the defect site, causing off target side effects and cytotoxicity. Gene therapy involves the introduction of foreign genes into a cell in order to exert an effect; either replacing a missing gene or modulating expression of a protein. State of the art gene therapy also encompasses manipulation of the transcriptome by harnessing RNA interference (RNAi) therapy. The delivery of nucleic acid nanomedicines on biomaterial scaffolds - gene-activated scaffolds -has shown potential for use in a variety of tissue engineering applications, but as of yet, have not reached clinical use. The current state of the art in terms of biomaterial scaffolds and delivery vector materials for gene therapy is reviewed, and the limitations of current procedures discussed. Future directions in the clinical translation of gene activated scaffolds are also considered, with a particular focus on bone and cartilage tissue regeneration. PMID- 26840619 TI - Reduced Uranium Phases Produced from Anaerobic Reaction with Nanoscale Zerovalent Iron. AB - Nanoscale zerovalent iron (nZVI) has shown potential to be an effective remediation agent for uranium-contaminated subsurface environments, however, the nature of the reaction products and their formation kinetics have not been fully elucidated over a range of environmentally relevant conditions. In this study, the oxygen-free reaction of U(VI) with varying quantities of nZVI was examined at pH 7 in the presence of both calcium and carbonate using a combination of X-ray absorption spectroscopy, X-ray diffraction and transmission electron microscopy. It was observed that the structure of the reduced U solid phases was time dependent and largely influenced by the ratio of nZVI to U in the system. At the highest U:Fe molar ratio examined (1:4), nanoscale uraninite (UO2) was predominantly formed within 1 day of reaction. At lower U:Fe molar ratios (1:21), evidence was obtained for the formation of sorbed U(IV) and U(V) surface complexes which slowly transformed to UO2 nanoparticles that were stable for up to 1 year of anaerobic incubation. After 8 days of reaction at the lowest U:Fe molar ratio examined (1:110), sorbed U(IV) was still the major form of U associated with the solid phase. Regardless of the U:Fe molar ratio, the anaerobic corrosion of nZVI resulted in the slow formation of micron-sized fibrous chukanovite (Fe2(OH)2CO3) particles. PMID- 26840620 TI - Ontogenetic Variation in the Thermal Biology of Yarrow's Spiny Lizard, Sceloporus jarrovii. AB - Climate change is rapidly altering the way current species interact with their environment to satisfy life-history demands. In areas anticipated to experience extreme warming, rising temperatures are expected to diminish population growth, due either to environmental degradation, or the inability to tolerate novel temperature regimes. Determining how at risk ectotherms, and lizards in particular, are to changes in climate traditionally emphasizes the thermal ecology and thermal sensitivity of physiology of adult members of a population. In this study, we reveal ontogenetic differences in thermal physiological and ecological traits that have been used to anticipate how ectotherms will respond to climate change. We show that the thermal biological traits of juvenile Yarrow's Spiny Lizards (Sceloporus jarrovii) differ from the published estimates of the same traits for adult lizards. Juvenile S. jarrovii differ in their optimal performance temperature, field field-active body temperature, and critical thermal temperatures compared to adult S. jarrovii. Within juvenile S. jarrovii, males and females exhibit differences in field-active body temperature and desiccation tolerance. Given the observed age- and sex-related variation in thermal physiology, we argue that not including physiological differences in thermal biology throughout ontogeny may lead to misinterpretation of patterns of ecological or evolutionary change due to climate warming. Further characterizing the potential for ontogenetic changes in thermal biology would be useful for a more precise and accurate estimation of the role of thermal physiology in mediating population persistence in warmer environments. PMID- 26840621 TI - The role and regulatory mechanism of IL-1beta on the methylation of the NF2 gene in benign meningiomas and leptomeninges. AB - Methylation of the neurofibromatosis type 2 (NF2) gene in low-grade meningioma (WHO grade I) has crucial roles in tumorigenesis and development. Meningioma formation might also occur in the setting of an inflammatory microenvironment. However, the association between inflammation and the methylation of NF2 remains unclear. The present study investigates the role and regulatory mechanism of IL 1beta, one of the most important pro-inflammatory cytokines, in the methylation of NF2 in benign meningioma. Three primary low-grade meningioma cells and leptomeningeal cells were cultured. CCK-8 and BrdU assays demonstrated that proliferation of meningioma/leptomeningeal cells treated with IL-1beta occurred in a dose- and time-dependent manner. Methylation-specific PCR verified that IL 1beta induced methylation of the NF2 promoter and decreased NF2/merlin expression in meningioma/leptomeningeal cells. Real-time PCR, western blotting, and immunofluorescence showed that IL-1beta up-regulated DNMT1 in meningioma cells and DNMT1/3b in leptomeningeal cells but did not up-regulate DNMT3a. After co treatment with the DNMT inhibitor 5-Aza-2'-deoxycytidine and DNMT siRNA, methylation of NF2 induced by IL-1beta was attenuated and merlin expression was restored. Furthermore, we showed that DNMT1 in meningiomas and DNMT1/3b in leptomeninges were regulated via activation of the MAPK (p38, ERK, JNK) and NF kappaB pathways. These results suggest that IL-1beta induces methylation of NF2 by up-regulating DNMT1 in benign meningioma cells and DNMT1/3b in leptomeningeal cells via MAPK and NF-kappaB pathways. Therefore, NF2 methylation is a linker between IL-1beta and tumor development, and DNMTs might be potential therapeutic targets in meningioma for regulating NF2 and inhibiting tumor development. (c) 2016 Wiley Periodicals, Inc. PMID- 26840622 TI - Preparation of a novel sorptive stir bar based on vinylpyrrolidone-ethylene glycol dimethacrylate monolithic polymer for the simultaneous extraction of diazepam and nordazepam from human plasma. AB - A new monolithic coating based on vinylpyrrolidone-ethylene glycol dimethacrylate polymer was introduced for stir bar sorptive extraction. The polymerization step was performed using different contents of monomer, cross-linker and porogenic solvent, and the best formulation was selected. The quality of the prepared vinylpyrrolidone-ethylene glycol dimethacrylate stir bars was satisfactory, demonstrating good repeatability within batch (relative standard deviation < 3.5%) and acceptable reproducibility between batches (relative standard deviation < 6.0%). The prepared stir bar was utilized in combination with ultrasound assisted liquid desorption, followed by high-performance liquid chromatography with ultraviolet detection for the simultaneous determination of diazepam and nordazepam in human plasma samples. To optimize the extraction step, a three level, four-factor, three-block Box-Behnken design was applied. Under the optimum conditions, the analytical performance of the proposed method displayed excellent linear dynamic ranges for diazepam (36-1200 ng/mL) and nordazepam (25-1200 ng/mL), with correlation coefficients of 0.9986 and 0.9968 and detection limits of 12 and 10 ng/mL, respectively. The intra- and interday recovery ranged from 93 to 106%, and the relative standard deviations were less than 6%. Finally, the proposed method was successfully applied to the analysis of diazepam and nordazepam at their therapeutic levels in human plasma. The novelty of this study is the improved polarity of the stir bar coating and its application for the simultaneous extraction of diazepam and its active metabolite, nordazepam in human plasma sample. The method was more rapid than previously reported stir bar sorptive extraction techniques based on monolithic coatings, and exhibited lower detection limits in comparison with similar methods for the determination of diazepam and nordazepam in biological fluids. PMID- 26840623 TI - Designing Supported Ionic Liquids (ILs) within Inorganic Nanosheets for CO2 Capture Applications. AB - A new methodology was developed for the immobilization of ionic liquids (ILs) on alpha-zirconium phosphate (ZrP) and montmorillonite (MMT) single-layer nanosheets via a facile coassembly process. The coassembled inorganic nanosheet/1-n-butyl-3 methylimidazolium chloride (BMIMCl) hybrids were systematically characterized. The results showed that the ILs were successfully assembled with ZrP or MMT single-layer nanosheets to form an intercalated structure. The inorganic nanosheet/IL hybrids can serve as efficient CO2 absorbents. The CO2 sorption of BMIMCl could be made up to 21 times more efficient because of the high exposure of the functional groups of BMIMCl in the coassembled hybrids. CO2 was physically absorbed by the hybrids with a slow equilibrium time at lower temperatures, whereas higher temperatures allowed for faster diffusion and chemical absorption of CO2. The best CO2 capture capacities of the hybrids were 0.73 mmol/g at 60 degrees C for ZrP/BMIMCl and 0.42 mmol/g at 70 degrees C for MMT/BMIMCl. PMID- 26840624 TI - Carcinogenesis associated with parasites other than Schistosoma, Opisthorchis and Clonorchis: A systematic review. AB - Only three helminths (Schistosoma haematobium, Opisthorchis viverrini and Clonorchis sinensis) are directly associated with carcinogenesis in humans whereas the role of other parasites in cancer remains unclear. This study aimed to perform a systematic review to identify recent insights in the role of other parasite infections in carcinogenesis. We conducted systematic searches of MEDLINE and EMBASE on July 2015. Our primary outcome was the association between parasitic infections and carcinogenesis. Out of 1,266 studies, 19 were selected for detailed evaluation (eight for helminths and 11 for protozoa). The mechanisms of helminth-induced cancer included chronic inflammation, sustained proliferation, modulation of the host immune system, reprogramming of glucose metabolism and redox signaling, induction of genomic instability and destabilization of suppressor tumor proteins, stimulation of angiogenesis, resisting cell death, and activation of invasion and metastasis. In addition to the current knowledge, the following parasites were found in cancers or tumors: Echinococcus, Strongyloides, Fasciola, Heterakis, Platynosomum and Trichuris. Additional parasites were found in this systematic review that could potentially be associated with cancers or tumors but further evidence is needed to elaborate a cause-effect relationship. PMID- 26840626 TI - The Electric Field of CO Tips and Its Relevance for Atomic Force Microscopy. AB - Metal tips decorated with CO molecules have paved the way for an impressively high resolution in atomic force microscopy (AFM). Although Pauli repulsion and the associated CO tilting play a dominant role at short distances, experiments on polar and metallic systems show that electrostatic interactions are necessary to understand the complex contrast observed and its distance evolution. Attempts to describe those interactions in terms of a single electrostatic dipole replacing the tip have led to contradictory statements about its nature and strength. Here, we solve this puzzle with a comprehensive experimental and theoretical characterization of the AFM contrast on Cl vacancies. Our model, based on density functional theory (DFT) calculations, reproduces the complex evolution of the contrast between both the Na cation and Cl anion sites, and the positively charged vacancy as a function of tip height, and highlights the key contribution of electrostatic interactions for tip-sample distances larger than 500 pm. For smaller separations, Pauli repulsion and the associated CO tilting start to dominate the contrast. The electrostatic field of the CO-metal tip can be represented by the superposition of the fields from the metal tip and the CO molecule. The long-range behavior is defined by the metal tip that contributes the field of a dipole with its positive pole at the apex. At short-range, the CO exhibits an opposite field that prevails. The interplay of these fields, with opposite sign and rather different spatial extension, is crucial to describe the contrast evolution as a function of the tip height. PMID- 26840625 TI - The Role of Synaptopodin in Membrane Protein Diffusion in the Dendritic Spine Neck. AB - The dynamic exchange of neurotransmitter receptors at synapses relies on their lateral diffusion in the plasma membrane. At synapses located on dendritic spines this process is limited by the geometry of the spine neck that restricts the passage of membrane proteins. Biochemical compartmentalisation of the spine is believed to underlie the input-specificity of excitatory synapses and to set the scale on which functional changes can occur. Synaptopodin is located predominantly in the neck of dendritic spines, and is thus ideally placed to regulate the exchange of synaptic membrane proteins. The central aim of our study was to assess whether the presence of synaptopodin influences the mobility of membrane proteins in the spine neck and to characterise whether this was due to direct molecular interactions or to spatial constraints that are related to the structural organisation of the neck. Using single particle tracking we have identified a specific effect of synaptopodin on the diffusion of metabotropic mGluR5 receptors in the spine neck. However, super-resolution STORM/PALM imaging showed that this was not due to direct interactions between the two proteins, but that the presence of synaptopodin is associated with an altered local organisation of the F-actin cytoskeleton, that in turn could restrict the diffusion of membrane proteins with large intracellular domains through the spine neck. This study contributes new data on the way in which the spine neck compartmentalises excitatory synapses. Our data complement models that consider the impact of the spine neck as a function of its shape, by showing that the internal organisation of the neck imposes additional physical barriers to membrane protein diffusion. PMID- 26840627 TI - Depression and Multiple Rehospitalizations in Patients With Heart Failure. AB - BACKGROUND: There have been few studies of the effect of depression on rehospitalization in patients with heart failure (HF), and even fewer on its role in multiple rehospitalizations. HYPOTHESIS: Depression is an independent risk factor for multiple readmissions in patients with HF. METHODS: A cohort of 662 patients with HF who were discharged alive after hospitalization were interviewed to evaluate symptoms of depression and were followed for 1 year. All-cause readmissions were documented by chart review. A marginal proportional rates model was used to model the effect of depression on the rate of rehospitalization with adjustment for known predictors of HF outcomes. RESULTS: Depression symptoms predicted multiple readmissions (adjusted hazard ratio [HR]: 1.08, 95% confidence interval [CI]: 1.03-1.13, P = 0.0008). Compared with patients without depression, those who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depression at index were at the highest risk for multiple rehospitalizations (HR: 1.51, 95% CI: 1.15-1.97, P = 0.003). CONCLUSIONS: Depression is an independent risk factor for multiple all-cause readmissions in patients with HF. PMID- 26840629 TI - Enhancement of Open-Circuit Voltage by Using the 58-pi Silylmethyl Fullerenes in Small-Molecule Organic Solar Cells. AB - The application of 58-pi-1,4-bis(silylmethyl)[60]fullerenes, C60 (CH2 SiMe2 Ph)(CH2 SiMe2 Ar) (Ar=Ph and 2-methoxylphenyl for SIMEF-1 and SIMEF-2, respectively), in small-molecule organic solar cells with a diketopyrrolopyrrole donor (3,6-bis[5-(benzofuran-2-yl)thiophen-2-yl]-2,5-bis(2-ethylhexyl)pyrrolo[3,4 c]pyrrole-1,4-dione (DPP(TBFu)2 )) is demonstrated. With the 58-pi-silylmethyl fullerene acceptor, SIMEF-1, the devices showed the highest efficiency of 4.57 % with an average of 4.10 %. They manifested an improved open-circuit voltage (1.03 V) owing to the high-lying LUMO level of SIMEF-1, while maintaining a high short circuit density (9.91 mA cm(-2) ) through controlling the crystallinity of DPP by thermal treatment. On the other hand, despite even higher open-circuit voltage (1.05 V), SIMEF-2-based devices showed lower performances of 3.53 %, owing to a low short-circuit current density (8.33 mA cm(-2) ) and fill factor (0.40) arising from the asymmetric structure, which results in a lower mobility and immiscibility. PMID- 26840628 TI - Asymmetric dimethylarginine (ADMA) elevation and arginase up-regulation contribute to endothelial dysfunction related to insulin resistance in rats and morbidly obese humans. AB - KEY POINTS: The presence of insulin resistance (IR) is determinant for endothelial dysfunction associated with obesity. Although recent studies have implicated the involvement of mitochondrial superoxide and inflammation in the defective nitric oxide (NO)-mediated responses and subsequent endothelial dysfunction in IR, other mechanisms could compromise this pathway. In the present study, we assessed the role of asymmetric dimethylarginine (ADMA) and arginase with respect to IR-induced impairment of endothelium-dependent vasodilatation in human morbid obesity and in a non-obese rat model of IR. We show that both increased ADMA and up-regulated arginase are determinant factors in the alteration of the l-arginine/NO pathway associated with IR in both models and also that acute treatment of arteries with arginase inhibitor or with l-arginine significantly alleviate endothelial dysfunction. These results help to expand our knowledge regarding the mechanisms of endothelial dysfunction that are related to obesity and IR and establish potential therapeutic targets for intervention. ABSTRACT: Insulin resistance (IR) is determinant for endothelial dysfunction in human obesity. Although we have previously reported the involvement of mitochondrial superoxide and inflammation, other mechanisms could compromise NO mediated responses in IR. We evaluated the role of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) and arginase with respect to IR-induced impairment of l-arginine/NO-mediated vasodilatation in human morbid obesity and in a non-obese rat model of IR. Bradykinin-induced vasodilatation was evaluated in microarteries derived from insulin-resistant morbidly obese (IR-MO) and non insulin-resistant MO (NIR-MO) subjects. Defective endothelial vasodilatation in IR-MO was improved by l-arginine supplementation. Increased levels of ADMA were detected in serum and adipose tissue from IR-MO. Serum ADMA positively correlated with IR score and negatively with pD2 for bradykinin. Gene expression determination by RT-PCR revealed not only the decreased expression of ADMA degrading enzyme dimethylarginine dimethylaminohydrolase (DDAH)1/2 in IR-MO microarteries, but also increased expression of arginase-2. Arginase inhibition improved endothelial vasodilatation in IR-MO. Analysis of endothelial vasodilatation in a non-obese IR model (fructose-fed rat) confirmed an elevation of circulating and aortic ADMA concentrations, as well as reduced DDAH aortic content and increased aortic arginase activity in IR. Improvement of endothelial vasodilatation in IR rats by l-arginine supplementation and arginase inhibition provided functional corroboration. These results demonstrate that increased ADMA and up-regulated arginase contribute to endothelial dysfunction as determined by the presence of IR in human obesity, most probably by compromising arginine availability. The results provide novel insights regarding the mechanisms of endothelial dysfunction related to obesity and IR and establish potential therapeutic targets for intervention. PMID- 26840630 TI - Forgotten value of the rapid, inexpensive, and lineage specific myeloperoxidase cytochemical stain in urgent clinical scenarios. PMID- 26840631 TI - An examination of the relation between intraocular pressure, fundal stretching and myopic pathology. AB - Pathological myopia is one of the leading causes of visual impairment worldwide. Myopic development and progression is biomechanical and dominated by axial elongation. This clinical perspective examines some of the stretch-related fundal changes, which are associated with axial elongation and myopic pathology. The biomechanics of stretching of the fundus appears to depend on genetically and/or visual experience-based scleral changes, which reduce its thickness and elastic modulus so that it becomes more susceptible to the distending forces of intraocular pressure. These changes include reduced collagen synthesis, altered collagen fibres, tissue loss, altered proteoglycans and increased matrix metalloproteinase activity. Such changes are associated with reduced scleral rigidity and related increased potential to stretch in response to intraocular pressure. As axial elongation progresses, the sclera appears likely to continue to reduce in thickness and in its capacity to resist intraocular pressure, especially when pressure becomes elevated. Tessellation, lacquer cracks, myopic crescents, staphylomata, chorioretinal atrophy and retinal detachment are examined within a model for stretching of the fundus. Age, refractive error and axial length, for example, are associated with increased pathological progression. Myopic pathological progression can become dominated by vascular changes and include a greater risk of loss of acuity and blindness. Measures to control myopic pathology, which successfully slow or prevent stretching of the fundus, appear to be key factors in reducing or even avoiding permanent visual loss associated with this condition. For example, limiting axial elongation and related myopic fundus pathology by inhibiting changes which reduce the elastic modulus of scleral tissue is a desirable outcome from interventions to control myopia. Similarly, reducing exposure to the distending stress of elevated intraocular pressure appears to be a desirable form of intervention to control myopia, especially if myopic pathology can be reduced or prevented. PMID- 26840633 TI - Osteopathology in Rhinocerotidae from 50 Million Years to the Present. AB - Individual elements of many extinct and extant North American rhinocerotids display osteopathologies, particularly exostoses, abnormal textures, and joint margin porosity, that are commonly associated with localized bone trauma. When we evaluated six extinct rhinocerotid species spanning 50 million years (Ma), we found the incidence of osteopathology increases from 28% of all elements of Eocene Hyrachyus eximius to 65-80% of all elements in more derived species. The only extant species in this study, Diceros bicornis, displayed less osteopathologies (50%) than the more derived extinct taxa. To get a finer-grained picture, we scored each fossil for seven pathological indicators on a scale of 1 4. We estimated the average mass of each taxon using M1-3 length and compared mass to average pathological score for each category. We found that with increasing mass, osteopathology also significantly increases. We then ran a phylogenetically-controlled regression analysis using a time-calibrated phylogeny of our study taxa. Mass estimates were found to significantly covary with abnormal foramen shape and abnormal bone textures. This pattern in osteopathological expression may reflect a part of the complex system of adaptations in the Rhinocerotidae over millions of years, where increased mass, cursoriality, and/or increased life span are selected for, to the detriment of long-term bone health. This work has important implications for the future health of hoofed animals and humans alike. PMID- 26840634 TI - The Role of a Nonribosomal Peptide Synthetase in l-Lysine Lactamization During Capuramycin Biosynthesis. AB - Capuramycins are one of several known classes of natural products that contain an l-Lys-derived l-alpha-amino-E-caprolactam (l-ACL) unit. The alpha-amino group of l-ACL in a capuramycin is linked to an unsaturated hexuronic acid component through an amide bond that was previously shown to originate by an ATP independent enzymatic route. With the aid of a combined in vivo and in vitro approach, a predicted tridomain nonribosomal peptide synthetase CapU is functionally characterized here as the ATP-dependent amide-bond-forming catalyst responsible for the biosynthesis of the remaining amide bond present in l-ACL. The results are consistent with the adenylation domain of CapU as the essential catalytic component for l-Lys activation and thioesterification of the adjacent thiolation domain. However, in contrast to expectations, lactamization does not require any additional domains or proteins and is likely a nonenzymatic event. The results set the stage for examining whether a similar NRPS-mediated mechanism is employed in the biosynthesis of other l-ACL-containing natural products and, just as intriguingly, how spontaneous lactamization is avoided in the numerous NRPS-derived peptides that contain an unmodified l-Lys residue. PMID- 26840635 TI - Monocyte infiltration into obese and fibrilized tissues is regulated by PILRalpha. AB - Paired immunoglobulin-like type 2 receptor alpha (PILRalpha) is an inhibitory receptor that is mainly expressed on myeloid cells, and negatively regulates neutrophil infiltration during inflammation. However, PILRalpha role on monocyte has not been described. Under both steady-state and inflammatory conditions, monocytes migrate into tissues and differentiate into macrophages. Macrophages in adipose and liver tissues play important roles in tissue homeostasis and pathogenesis of metabolic diseases. Here, we found that PILRalpha controls monocyte mobility through regulating integrin signaling and inhibiting CD99-CD99 binding. Moreover, we found that Pilra(-/-) mice developed obesity and hepatomegaly with fibrosis, and the numbers of macrophages in adipose and liver tissues are significantly increased in Pilra(-/-) mice. These data suggest that immune inhibitory receptor, PILRalpha, plays an important role in the prevention of obesity and liver fibrosis. PMID- 26840636 TI - Mutational screening of the INSL3 gene in azoospermic males with a history of cryptorchidism. AB - The insulin-like factor 3 (INSL3 ) gene encodes 131 amino acids, consisting of two exons. In human beings, mutations of this gene may lead to bilateral cryptorchidism and infertility. However, the role of INSL3 in male spermatogenesis still remains controversial. We have analysed the coding sequence of INSL3 by PCR and DNA sequencing in 97 azoospermic patients with a history of bilateral cryptorchidism (patient group) versus 49 males with obstructive azoospermia (control group). The G178A mutation, which were predicted to alter the protein sequence (alanine to threonine), was detected in the patient group but not in the control group. While synonymous mutations G27A and G126A were detected in the control group, each occurred only in a single sample. When the patient group were divided into two subgroups according to the testicular biopsy result: sperm+ subgroup (51 cases with spermatozoa can be detected) or sperm- subgroup (46 cases with spermatozoa could not be detected). The INSL3 G178A polymorphism was not significantly associated with spermatozoa or no spermatozoa in the testes of males with a history of bilateral cryptorchidism. In conclusion, the evidence suggests that mutations of INSL3 may not directly contribute to the damage of spermatogenesis in patients with bilateral cryptorchidism history. PMID- 26840632 TI - Biomass resilience of Neotropical secondary forests. AB - Land-use change occurs nowhere more rapidly than in the tropics, where the imbalance between deforestation and forest regrowth has large consequences for the global carbon cycle. However, considerable uncertainty remains about the rate of biomass recovery in secondary forests, and how these rates are influenced by climate, landscape, and prior land use. Here we analyse aboveground biomass recovery during secondary succession in 45 forest sites and about 1,500 forest plots covering the major environmental gradients in the Neotropics. The studied secondary forests are highly productive and resilient. Aboveground biomass recovery after 20 years was on average 122 megagrams per hectare (Mg ha(-1)), corresponding to a net carbon uptake of 3.05 Mg C ha(-1) yr(-1), 11 times the uptake rate of old-growth forests. Aboveground biomass stocks took a median time of 66 years to recover to 90% of old-growth values. Aboveground biomass recovery after 20 years varied 11.3-fold (from 20 to 225 Mg ha(-1)) across sites, and this recovery increased with water availability (higher local rainfall and lower climatic water deficit). We present a biomass recovery map of Latin America, which illustrates geographical and climatic variation in carbon sequestration potential during forest regrowth. The map will support policies to minimize forest loss in areas where biomass resilience is naturally low (such as seasonally dry forest regions) and promote forest regeneration and restoration in humid tropical lowland areas with high biomass resilience. PMID- 26840637 TI - Routine weighing to reduce excessive antenatal weight gain: a randomised controlled trial. AB - OBJECTIVE: To assess whether routinely weighing women at each antenatal visit leads to a difference in gestational weight gain and weight gain within the Institute of Medicine (IOM) recommendation. DESIGN: A randomised controlled trial. SETTING: Antenatal clinics in a tertiary obstetric hospital in Melbourne, Australia. POPULATION: Healthy women were enrolled during their antenatal booking visit if they were between 18 and 45 years of age, were <21 weeks' gestation with a singleton pregnancy. METHODS: The intervention was weighing at each antenatal clinic appointment followed by counselling by their treating clinician according to IOM gestational weight gain guidelines. The control group had standard antenatal care comprising recording weight at booking and then at 36 weeks. Primary analysis was by intention-to-treat. OUTCOME: The primary outcome was difference in mean weight gain between groups. An important secondary outcome was gestational weight gain within IOM recommendations. Secondary outcomes also included maternal or neonatal morbidity. RESULTS: Seven hundred and eighty two women consented to take part and 386 were randomised to the intervention group and 396 to the control group. There was no significant difference in weight gain between the intervention group (0.54 kg/week) compared with the control group (0.53 kg/week) (P = 0.63). A similar proportion of women gained more weight than the IOM recommended range: 75% in the intervention group and 71% in the control group (P = 0.21). There were no significant differences in secondary outcomes between the two groups. CONCLUSION: We found no evidence that regular weighing in antenatal clinics changed weight gain or was effective at reducing excessive gestational weight gain. PMID- 26840638 TI - Correction: Animal Ownership and Touching Enrich the Context of Social Contacts Relevant to the Spread of Human Infectious Diseases. PMID- 26840639 TI - Cross-Sectional Analysis of the 1039 U.S. Physicians Reported to the National Practitioner Data Bank for Sexual Misconduct, 2003-2013. AB - BACKGROUND: Little information exists on U.S. physicians who have been disciplined with licensure or restriction-of-clinical-privileges actions or have had malpractice payments because of sexual misconduct. Our objectives were to: (1) determine the number of these physicians and compare their age groups' distribution with that of the general U.S. physician population; (2) compare the type of disciplinary actions taken against these physicians with actions taken against physicians disciplined for other offenses; (3) compare the characteristics and type of injury among victims of these physicians with those of victims in reports for physicians with other offenses in malpractice-payment reports; and (4) determine the percentages of physicians with clinical-privileges or malpractice-payment reports due to sexual misconduct who were not disciplined by medical boards. METHODS AND RESULTS: We conducted a cross-sectional analysis of physician reports submitted to the National Practitioner Data Bank (NPDB) from January 1, 2003, through September 30, 2013. A total of 1039 physicians had >= 1 sexual-misconduct-related reports. The majority (75.6%) had only licensure reports, and 90.1% were 40 or older. For victims in malpractice-payment reports, 87.4% were female, and "emotional injury only" was the predominant type of injury. We found a higher percentage of serious licensure actions and clinical privileges revocations in sexual-misconduct-related reports than in reports for other offenses (89.0% vs 68.1%, P = < .001, and 29.3% vs 18.8%, P = .002, respectively). Seventy percent of the physicians with a clinical-privileges or malpractice-payment report due to sexual misconduct were not disciplined by medical boards for this problem. CONCLUSIONS: A small number of physicians were reported to the NPDB because of sexual misconduct. It is concerning that a majority of the physicians with a clinical-privileges action or malpractice payment report due to sexual misconduct were not disciplined by medical boards for this unethical behavior. PMID- 26840641 TI - Dog ownership status and self-assessed health, life-style and habitual physical activity in chronic hemodialysis patients. AB - Introduction The Statement from the American Heart Association has emphasized a need for novel strategies that can reduce the risk of cardiovascular disease (CVD). Taking a dog for a walk forces its owner to take physical activity. Several studies have explored the relationship between pet ownership and CVD and most reported benefits. This issue has not been investigated in dialysis patients. The aim of the study was to analyze the influence of pet ownership on health and physical activity in hemodialysis patients. Methods 270 chronic hemodialysis patients (172 male, 98 female, mean age 62.7 +/- 14.0 years, hemodialysis vintage 4 +/- 5 years) took part in the survey focused on their general health and physical activity. Findings Two hundred nineteen (81%) patients were mobile. One hundred sixteen participants had dog at home (43%). An additional physical activity was reported by 46 dog owners (40%) compared with 34 (23%) of nonowners (P = 0.002). Patients who often go for a walk were more often pet owners 49 (57%) than nonowners (n = 37, 43%; P = 0.004). Pet owners were younger (58.3 +/- 13.6 vs. 66 +/- 13.5 years). Body mass index (BMI) was similar. Patients with BMI from upper tertile (>27.5 kg/m(2) ) and from lower (<23.9) were more often dog owners than from the middle (52.9%, 43.7%, and 31.4%). Dog owners were on dialysis for longer time (5.0 +/- 6.5 vs. 3.5 +/- 3.7 years; P = 0.02). Discussion Dog ownership appears to positively influence the level of physical activity. Age but not time on dialysis seems to be the most important factor that influences a decision to own a pet and undertake physical activity. PMID- 26840640 TI - Characterising Complex Enzyme Reaction Data. AB - The relationship between enzyme-catalysed reactions and the Enzyme Commission (EC) number, the widely accepted classification scheme used to characterise enzyme activity, is complex and with the rapid increase in our knowledge of the reactions catalysed by enzymes needs revisiting. We present a manual and computational analysis to investigate this complexity and found that almost one third of all known EC numbers are linked to more than one reaction in the secondary reaction databases (e.g., KEGG). Although this complexity is often resolved by defining generic, alternative and partial reactions, we have also found individual EC numbers with more than one reaction catalysing different types of bond changes. This analysis adds a new dimension to our understanding of enzyme function and might be useful for the accurate annotation of the function of enzymes and to study the changes in enzyme function during evolution. PMID- 26840642 TI - Superfertility is more prevalent in obese women with recurrent early pregnancy miscarriage. AB - OBJECTIVE: To investigate the effects of obesity on superfertility. DESIGN: Retrospective observational study. SETTING: A tertiary referral implantation clinic. POPULATION: Four hundred and fourteen women attending a tertiary implantation clinic with a history of recurrent miscarriage (RMC), over a 4-year period. METHODS: Pattern of pregnancy loss and time to pregnancy intervals for each pregnancy were collected by medical staff from women with RMC. The women were categorised into normal, overweight and obese according to their body mass index (BMI). Kaplan-Meier curves were constructed estimating the cumulative probability of a spontaneous pregnancy over time. The pregnancy loss patterns were correlated with BMI and data were compared between the categories using the Kruskal-Wallis test. MAIN OUTCOME MEASURES: Pregnancy loss pattern and time to pregnancy intervals. RESULTS: Overall, 23.2, 51.4 and 64.2% of women conceived within first 1, 3 and 6 months, respectively. Obese women had cumulative pregnancy rates of 65.2 and 80% by three and 6 months, respectively, which was more than the cumulative pregnancy rates for women with normal BMI (49.2 and 65.8%). Comparison of survival curves indicated a significant difference in time to conceive for obese when compared with normal and overweight women (*P = 0.01), suggesting a higher prevalence of superfertility in obese women with RMC. CONCLUSIONS: Our findings suggest that obese women may have a greater efficacy to achieve pregnancy, but with an increased risk of miscarriage, which may suggest the possible metabolic effects of obesity on endometrium. PMID- 26840643 TI - Erratum. Cyclic adenosine monophosphate-mediated enhancement of vascular endothelial growth factor released by differentiated human monocytic cells: the role of protein kinase A. PMID- 26840645 TI - Multiscale Modeling of the Effect of Pressure on the Interfacial Tension and Other Cohesion Parameters in Binary Mixtures. AB - We study and predict the interfacial tension, solubility parameters, and Flory Huggins parameters of binary mixtures as functions of pressure and temperature, using multiscale numerical simulation. A mesoscopic approach is proposed for simulating the pressure dependence of the interfacial tension for binary mixtures, at different temperatures, using classical dissipative particle dynamics (DPD). The thermodynamic properties of real systems are reproduced via the parametrization of the repulsive interaction parameters as functions of pressure and temperature via molecular dynamics simulations. Using this methodology, we calculate and analyze the cohesive energy density and the solubility parameters of different species obtaining excellent agreement with reported experimental behavior. The pressure- and temperature-dependent Flory Huggins and repulsive DPD interaction parameters for binary mixtures are also obtained and validated against experimental data. This multiscale methodology offers the benefit of being applicable for any species and under difficult or nonfeasible experimental conditions, at a relatively low computational cost. PMID- 26840644 TI - Topical Timolol for Infantile Hemangiomas: Evidence for Efficacy and Degree of Systemic Absorption. AB - BACKGROUND: Topical use of timolol for infantile hemangiomas has recently emerged with promising results. It is unknown whether topical beta-blockers act locally or if their effect is partly due to systemic absorption. This study investigates whether topically applied timolol is absorbed and reports on the efficacy of this treatment. METHODS: We treated 40 infants with small proliferating hemangiomas with topical timolol gel 0.5% twice daily and assessed urinary excretion and serum levels in a proportion of patients. Clinical response was evaluated on a visual analog scale of standardized photographs after 1, 2, 3, and 5 months. RESULTS: Forty infants with a median age of 18 weeks (range 2-35 wks) were included; 23 (58%) had superficial and 17 (42%) mixed-type hemangiomas. The median size was 3 cm(2) (range 0.1-15 cm(2) ) and nine hemangiomas were ulcerated. The hemangiomas improved significantly during treatment, with a median increase in visual analog scale of 7 points after 5 months (p < 0.001). Urinalysis for timolol was performed in 24 patients and was positive in 20 patients (83%). In three infants, serum levels of timolol were also measured and were all positive (median 0.16 ng/mL [range 0.1-0.18 ng/mL]). No significant side effects were recorded. CONCLUSION: Topical therapy with timolol is effective for infantile hemangiomas, but systemic absorption occurs. Serum levels in our patients were low, suggesting that using timolol for small hemangiomas is safe, but caution is advised when treating ulcerated or large hemangiomas, very young infants, or concomitantly using systemic propranolol. PMID- 26840646 TI - Early Cretaceous Umkomasia from Mongolia: implications for homology of corystosperm cupules. AB - Corystosperms, a key extinct group of Late Permian to Early Cretaceous plants, are important for understanding seed plant phylogeny, including the evolution of the angiosperm carpel and anatropous bitegmic ovule. Here, we describe a new species of corystosperm seed-bearing organ, Umkomasia mongolica sp. nov., based on hundreds of three-dimensionally preserved mesofossils from the Early Cretaceous of Mongolia. Individual seed-bearing units of U. mongolica consist of a bract subtending an axis that bifurcates, with each fork (cupule stalk) bearing a cupule near the tip. Each cupule is formed by the strongly reflexed cupule stalk and two lateral flaps that partially enclose an erect seed. The seed is borne at, or close to, the tip of the reflexed cupule stalk, with the micropyle oriented towards the stalk base. The corystosperm cupule is generally interpreted as a modified leaf that bears a seed on its abaxial surface. However, U. mongolica suggests that an earlier interpretation, in which the seed is borne directly on an axis (shoot), is equally likely. The 'axial' interpretation suggests a possible relationship of corystosperms to Ginkgo. It also suggests that the cupules of corystosperms may be less distinct from those of Caytonia than has previously been supposed. PMID- 26840647 TI - Decellularized human amniotic membrane: how viable is it as a delivery system for human adipose tissue-derived stromal cells? AB - OBJECTIVES: Human amniotic membrane (HAM) has been widely used in soft tissue engineering both in its fresh form and decellularized; its efficiency to aid treatment of burn injuries is well known. On the other hand, it has been reported clinically by several studies that human adipose-derived stem cells (hADSC) are a promising cell source for cell therapy for burns. Recently, we have reported a new technique for decellularization of HAM. In this study, potential of prepared decellularized HAM (dHAM) as a viable support for proliferation and delivery of hADSC was investigated. MATERIALS AND METHODS: Amniotic membranes were collected, decellularized and preserved according to the protocol described in our previously published study. hADSC were obtained from the patients undergoing elective liposuction surgery and cells were then seeded on the decellularized membrane for various times. Efficiency of the decellularized membrane as a delivery system for hADSC was investigated by MTT, LDH specific activity, DAPI staining and SEM. RESULTS: The results showed that dHAM provided a supporting microenvironment for cell growth without producing any cytotoxic effects. In addition, the cells were spread out and actively attached to the dHAM scaffold. CONCLUSION: These results strongly suggest that dHAMs have considerable potential as 3D cell-carrier scaffolds for delivery of hADSC, in tissue engineering and regenerative medicine applications. PMID- 26840649 TI - A Systematic Review of the Impact of Dedicated Emergency Surgical Services on Patient Outcomes. AB - OBJECTIVE: This review aims to assess the impact of implementing dedicated emergency surgical services, in particular acute care surgery, on clinical outcomes. BACKGROUND: The optimal model for delivering high-quality emergency surgical care remains unknown. Acute Care Surgery (ACS) is a health care model combining emergency general surgery, trauma, and critical care. It has been adopted across the United States in the management of surgical emergencies. METHOD: A systematic review was performed after PRISMA recommendations using the MEDLINE, Embase, and Psych-Info databases. Studies assessing different care models and institutional factors affecting the delivery of emergency general surgery were included. RESULTS: Twenty-seven studies comprising 744,238 patients were included in this review. In studies comparing ACS with traditional practice, mortality and morbidity were improved. Moreover, time to senior review, delays to operating theater, and financial expenditure were often reduced. The elements of ACS models varied but included senior clinicians present onsite during office hours and dedicated to emergency care while on-call. Referrals were made to specialist centers with primary surgical assessments taking place on surgical admissions units rather than in the emergency department. Twenty-four-hour access to dedicated emergency operating rooms was also described. CONCLUSIONS: ACS models as well as centralized units and hospitals with dedicated emergency operating rooms, access to radiology and intensive care facilities (ITU) are all factors associated with improved clinical and financial outcomes in the delivery of emergency general surgery. There is, however, no consensus on the elements that constitute an ideal ACS model and how it can be implemented into current surgical practice. PMID- 26840650 TI - Cooperativity in Noncovalent Interactions. PMID- 26840651 TI - Characterization of Cetyltrimethylammonium Bromide/Hexanol Reverse Micelles by Experimentally Benchmarked Molecular Dynamics Simulations. AB - Encapsulation of small molecules, proteins, and other macromolecules within the protective water core of reverse micelles is emerging as a powerful strategy for a variety of applications. The cationic surfactant cetyltrimethylammonium bromide (CTAB) in combination with hexanol as a cosurfactant is particularly useful in the context of solution NMR spectroscopy of encapsulated proteins. Small-angle X ray and neutron scattering is employed to investigate the internal structure of the CTAB/hexanol reverse micelle particle under conditions appropriate for high resolution NMR spectroscopy. The scattering profiles are used to benchmark extensive molecular dynamics simulations of this reverse micelle system and indicate that the parameters used in these simulations recapitulate experimental results. Scattering profiles and simulations indicate formation of homogeneous solutions of small approximately spherical reverse micelle particles at a water loading of 20 composed of ~150 CTAB and 240 hexanol molecules. The 3000 waters comprising the reverse micelle core show a gradient of translational diffusion that reaches that of bulk water at the center. Rotational diffusion is slowed relative to bulk throughout the water core, with the greatest slowing near the CTAB headgroups. The 5 A thick interfacial region of the micelle consists of overlapping layers of Br(-) enriched water, CTAB headgroups, and hexanol hydroxyl groups, containing about one-third of the total water. This study employs well parametrized MD simulations, X-ray and neutron scattering, and electrostatic theory to illuminate fundamental properties of CTAB/hexanol reverse micelle size, shape, partitioning, and water behavior. PMID- 26840652 TI - Modified penetrating keratoplasty with Acell(r) bioscaffold implant in seven horses with deep full-thickness corneal stromal abscess. AB - OBJECTIVE: To describe and evaluate a modified penetrating keratoplasty technique utilizing ACell(r) for management of equine deep stromal or full-thickness corneal stromal abscesses (SA). METHODS: Cases presenting to the University of Georgia Ophthalmology service for surgical management of SA necessitating penetrating keratoplasty (PK) were included in the study population. Surgery entailed the use of an ACell(r) disk sutured within the deep level of a stepped full-thickness corneal incision with an overlying conjunctival pedicle flap placed in the superficial step incision. Patients were evaluated for success as defined by a comfortable, visual outcome. RESULTS: Surgery was performed in seven horses. Conjunctival flap incorporation and globe retention occurred in all patients. Functional vision was maintained in six of seven eyes (85.7%) at last follow-up examination (mean of 87.6 days [range 41-251 days]). Mean size of ACell(r) implant was six millimeters (range 4-8 mm). Postoperative complications included moderate to severe anterior uveitis (n = 2), diffuse keratitis (n = 1), incipient cataract formation (n = 3), and anterior and posterior synechiae (n = 1). CONCLUSIONS: This technique is a viable option for treatment of equine SA requiring PK. The use of bioscaffold implant is an alternative to frozen and fresh donor cornea transplantation. PMID- 26840653 TI - Relationship of Bowel MR Imaging to Health-related Quality of Life Measures in Newly Diagnosed Pediatric Small Bowel Crohn Disease. AB - Purpose To determine if utility measures of health-related quality of life (HRQOL) in pediatric small bowel Crohn disease (a) change in response to infliximab therapy, (b) correlate with proxy parent or guardian assessments, and (c) correlate with magnetic resonance (MR) imaging and laboratory markers of intestinal active inflammation. Materials and Methods This prospective single center cohort study was approved by the institutional review board and was compliant with HIPAA. Parental informed consent and subject assent were obtained from all study participants. Twenty-six children with newly diagnosed small bowel Crohn disease receiving infliximab therapy were prospectively enrolled. All subjects underwent measurement of HRQOL utilities (visual analog scale [VAS], time trade-off [TTO], and standard gamble [SG]), MR enterography, and laboratory assessment at baseline and 6 months later. The Wilcoxon signed-rank test was used to compare paired nonparametric data; Spearman correlation (rho) was used to assess bivariate relationships. Results The median VAS score was 47.5 (interquartile range [IQR]: 20.0-52.2) before infliximab therapy and 83.0 (IQR: 62.0-92.0) at follow-up (P = .0003). There was positive correlation between subject and parent or guardian change in VAS score between baseline and follow-up (rho = 0.71; P = .0006). The authors identified significant negative correlations between VAS score and MR imaging bowel wall arterial phase enhancement after contrast material administration at baseline (rho = -0.57, P = .0032) as well as between change in VAS score and change in bowel wall enhancement in the arterial phase at contrast-enhanced MR imaging over time (rho = -0.51, P = .02). No correlations between VAS score and laboratory inflammatory markers were identified. Conclusion VAS assessment of HRQOL changes over time in response to infliximab therapy in children with small bowel Crohn disease. There are statistically significant correlations between child-reported VAS score and (a) the degree of bowel wall enhancement in the arterial phase at contrast-enhanced MR imaging and (b) parent or guardian assessment. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26840654 TI - Abdominal Imaging with Contrast-enhanced Photon-counting CT: First Human Experience. AB - PURPOSE: To evaluate the performance of a prototype photon-counting detector (PCD) computed tomography (CT) system for abdominal CT in humans and to compare the results with a conventional energy-integrating detector (EID). MATERIALS AND METHODS: The study was HIPAA-compliant and institutional review board-approved with informed consent. Fifteen asymptomatic volunteers (seven men; mean age, 58.2 years +/- 9.8 [standard deviation]) were prospectively enrolled between September 2 and November 13, 2015. Radiation dose-matched delayed contrast agent-enhanced spiral and axial abdominal EID and PCD scans were acquired. Spiral images were scored for image quality (Wilcoxon signed-rank test) in five regions of interest by three radiologists blinded to the detector system, and the axial scans were used to assess Hounsfield unit accuracy in seven regions of interest (paired t test). Intraclass correlation coefficient (ICC) was used to assess reproducibility. PCD images were also used to calculate iodine concentration maps. Spatial resolution, noise-power spectrum, and Hounsfield unit accuracy of the systems were estimated by using a CT phantom. RESULTS: In both systems, scores were similar for image quality (median score, 4; P = .19), noise (median score, 3; P = .30), and artifact (median score, 1; P = .17), with good interrater agreement (image quality, noise, and artifact ICC: 0.84, 0.88, and 0.74, respectively). Hounsfield unit values, spatial resolution, and noise-power spectrum were also similar with the exception of mean Hounsfield unit value in the spinal canal, which was lower in the PCD than the EID images because of beam hardening (20 HU vs 36.5 HU; P < .001). Contrast-to-noise ratio of enhanced kidney tissue was improved with PCD iodine mapping compared with EID (5.2 +/- 1.3 vs 4.0 +/- 1.3; P < .001). CONCLUSION: The performance of PCD showed no statistically significant difference compared with EID when the abdomen was evaluated in a conventional scan mode. PCD provides spectral information, which may be used for material decomposition. PMID- 26840655 TI - Pelvic venous congestion with castration causes chronic prostatitis in rats. AB - OBJECTIVE: To determine whether castration combined with pelvic congestion could cause chronic prostatitis, and to examine the effect of eviprostat in this rat model. METHODS: Male rats were divided into three groups, which were the sham, castration combined with pelvic congestion and castration combined with pelvic congestion plus eviprostat groups. Rats in the castration combined with pelvic congestion and castration combined with pelvic congestion plus eviprostat groups were anesthetized with isoflurane, after which ligation of the bilateral common iliac veins and castration were carried out. The sham and castration combined with pelvic congestion groups were fed a standard diet, whereas the castration combined with pelvic congestion plus eviprostat group was fed the same diet containing 0.1% eviprostat. After 4 weeks, continuous cystometry was carried out under urethane anesthesia. Then the bladder and the prostate gland were subjected to histological examination. RESULTS: There was no significant difference of the interval between bladder contractions in the sham and castration combined with pelvic congestion plus eviprostat groups, but the interval in the castration combined with pelvic congestion group was significantly shorter than the other groups. There was no difference in the maximum bladder contraction pressure among the three groups. Pathological inflammatory changes of the bladder wall were slightly more severe in the castration combined with pelvic congestion and castration combined with pelvic congestion plus eviprostat groups than in the sham group, whereas bladder vascularity was increased in the castration combined with pelvic congestion plus eviprostat group. In addition, pathological inflammatory changes and glandular atrophy of the prostate were more severe in the castration combined with pelvic congestion and castration combined with pelvic congestion plus eviprostat groups than in the sham group. CONCLUSION: This rat model of pelvic congestion with castration might assist in the development of new treatments for chronic prostatitis and frequency. PMID- 26840656 TI - The Hot-Water Extract of Smilacis Chinae Rhizome Suppresses 2,4 Dinitrochlorobenzene and House Dust Mite-Induced Atopic Dermatitis-Like Skin Lesions in Mice. AB - Smilacis Chinae Rhizome (SCR) has been used as an oriental folk medicine for various biological activities. However, its effect on atopic dermatitis (AD) remains undetermined to date. We assessed the effect of orally administered hot water extract of SCR on AD-like skin lesions in mice and its underlying mechanisms. AD-like murine model was prepared by repeated alternate application of house dust mite (Dermatophagoides farinae) extract (DFE) and 2,4 dinitrochlorobenzene (DNCB) for 4 weeks, topically to the ears. Daily oral administration of SCR for 3 and 4 weeks significantly reduced inflammatory ear thickening, with the effect being enhanced at the earlier start and longer period of administration. This effect was accompanied by a significant decrease in both Th2 and Th1 serum antibodies (total IgE, DFE-specific IgE, and IgG2a). Histological analysis showed that SCR markedly decreased the epidermal/dermal ear thickening and the dermal infiltration of inflammatory cells. Furthermore, SCR suppressed DFE/DNCB-induced expression of IL-4, IL-13, IL-17, IL-18, TSLP, and IFN-gamma genes in the ear tissue. Taken together, our observations demonstrate that chronic oral administration of SCR exerts beneficial effect in mouse AD model, suggesting that SCR has the therapeutic potential as an orally active treatment of AD by modulating both Th1 and Th2 responses. PMID- 26840657 TI - Residual activities of 99mTc-labelled radiopharmaceuticals in routine nuclear medicine practice. AB - INTRODUCTION: In this study, we present a series of common Tc-labelled radiopharmaceuticals administrations performed in a busy nuclear medicine department within a 1-year timeframe in routine practice. The main objective is to identify the true activity administered to the patient and whether that is in compliance with the EANM guidelines, where applicable, and/or with the department's protocols. As a secondary objective, we aimed to assess whether the volume of the injected dose correlates to the percentage of residual activity measured after injection for each studied radiotracer. MATERIALS AND METHODS: A number of commonly used Tc-labelled radiopharmaceuticals including Tc pertechnetate, Tc-methylenediphosphonic acid, Tc-hydroxymethylenediphosphonic acid, Tc-3,3-diphosphono-1,2-propanedicarboxylic acid, Tc-dimercaptosuccinic acid (DMSA), Tc-mercaptoacetyltriglycine, Tc-2-methoxyisobutylisonitrile (sestamibi), Tc-1,2-bis[bis(2-ethoxyethyl)phosphino]ethane (tetrofosmin) and Tc-HYNIC-Tyr octreotide (Tektrotyd) were assessed. All data were collected prospectively within a 1-year period under routine medical practice and included (a) injected activity, (b) residual activity, (c) percentage of residual activity (residual activity/injected activity*100), (d) effective activity (injected activity minus the residual activity), (e) injected volume, (f) time of injection and (g) type of procedure. RESULTS: In the 1837 collected measurements, the average percentage of residual activity was 13% (95% confidence interval: 12.75-13.39%). The mean effective activities were within the recommended range by the EANM guidelines, where applicable, or did not exceed the recommended doses from the department's protocols. In cases where actual injected activity was lower than the minimum suggested by the department's protocols, the imaging quality was not compromised. There was a negative correlation and thus an inverse relationship between the percentage of residual activity and administered volume for Tc-pertechnetate, Teceos, Bonescan, HDP, generic DMSA, RENOCIS, Nephromag and Tektrotyd (Spearman's r coefficient ranging from -0.311 to -0.561). Cardiologic radiotracers presented no such correlation. CONCLUSION: It should be possible to reduce the level of administered activity for the diagnostic examinations, but with consideration of the residual activity, especially for radiopharmaceuticals with a high mean residual activity (mainly tetrofosmin and sestamibi). PMID- 26840658 TI - Characterization of the Azirinyl Cation and Its Isomers. AB - The azirinyl cation (C2H2N(+)) and its geometrical isomers could be present in the interstellar medium. The C2H2N(+) isomers are, however, difficult to identify in interstellar chemistry because of the lack of high-resolution spectroscopic data from laboratory experiments. Ab initio quantum chemical methods were used to characterize the structures, relative energies, and spectroscopic and physical properties of the low energy isomers of the azirinyl cation. We have employed second-order Moller-Plesset perturbation theory (MP2), second-order Z-averaged perturbation theory (ZAPT2), and coupled cluster theory with singles and doubles with perturbative triples CCSD(T) methods along with large correlation consistent basis sets such as cc-pVTZ, cc-pCVTZ, cc-pVQZ, cc-pCVQZ, and cc-pV5Z. Harmonic vibrational frequencies, dipole moments, rotational constants, and proton affinities for the lowest energy isomers were calculated using the CCSD(T) method. Azirinyl cation, a cyclic isomer, is lowest in energy at all levels of theory employed. Azirinyl cation is followed by the cyanomethyl cation (H2CCN)(+), isocyanomethyl cation (H2CNC)(+), and a quasilinear HCCNH(+) cation, which are 13.8, 17.3, and 21.5 kcal mol(-1) above the cyclic isomer, respectively, at the CCSD(T)/cc-pV5Z level of theory. The lowest three isomers all have C2v symmetry and (1)A1 ground electronic states. The quasilinear HCCNH(+) cation has a Cs symmetry planar structure, and a (3)A" electronic ground state, unlike what some previous work suggested. PMID- 26840659 TI - Air in the Left Ventricle. An Unusual Case of Endocarditis. PMID- 26840660 TI - The endoscopic modified Lothrop procedure: finally ready for prime time in the management of inflammatory sinus disease. PMID- 26840661 TI - Ranolazine following percutaneous coronary intervention: For whom? For what? PMID- 26840662 TI - Ideal Start to Human Life. PMID- 26840663 TI - Centralized Newborn Hearing Screening in Ernakulam, Kerala , Experience Over a Decade. AB - A two-stage centralized newborn screening program was initiated in Cochin in January 2003. Infants are screened first with otoacoustic emission (OAE). Infants who fail OAE on two occasions are screened with auditory brainstem response (ABR). All Neonatal intensive care unit babies undergo ABR. This successful model subsequently got expanded to the whole district of Ernakulam, and some hospitals in Kottayam and Thrissur districts. Over the past 11 years, 1,01,688 babies were screened. Permanent hearing loss was confirmed in 162 infants (1.6 per 1000). This practical model of centralized newborn hearing screening may be replicated in other districts of our country or in other developing countries. PMID- 26840664 TI - Galactosemia , A Not to be Missed Inborn Error of Metabolism. PMID- 26840665 TI - Classic Galactosemia: Indian Scenario. PMID- 26840666 TI - The Revised Guidelines of the Medical Council of India for Academic Promotions: Need for a Rethink. PMID- 26840668 TI - Public Health Laboratory Surveillance and Diagnosis of Japanese Encephalitis: Time to Revisit. AB - OBJECTIVE: We assessed detection of recent Japanese encephalitis virus infection using recommended strategy. METHODS: Cross-sectional community-based study conducted in 12 villages in Kushinagar, Uttar-Pradesh, India in 2012-13. Recent infection with Japanese encephalitis virus in 239 healthy children aged 1-15 year was detected using a combination of serology and molecular methods. RESULTS: 24 (10%) children showed recent infection; 2 by serology and 22 by molecular method. Symptomatic cases were estimated as 626 in Kushinagar against reported 139 in all age groups across the state. CONCLUSIONS: Lower positivity using recommended serology suggests major gap in existing surveillance and diagnostic protocols and estimation of burden of Japanese encephalitis. PMID- 26840667 TI - Classical Galactosemia Among Indian Children: Presentation and Outcome from a Pediatric Gastroenterology Center. AB - OBJECTIVE: To analyze the presentation and predictors of outcome of children with galactosemia. METHODS: Analysis of clinical, laboratory, microbiological profile and outcome of patients fulfilling the diagnostic criteria: i) clinical setting; ii) reduced erythrocyte Gal-1-PUT enzyme activity; and iii) unequivocal response to lactose-free diet. RESULTS: 24 patients; median age of symptom onset and diagnosis: 10 (3-75) d and 55 (15-455) days, respectively. 71% had uncorrectable coagulopathy; 71% systemic infections; and 54% had ascites. CONCLUSION: Despite delayed referral, high Pediatric end-stage liver disease scores and systemic infections, long-term outcome in galactosemia is rewarding. A subset of children have developmental delay. PMID- 26840669 TI - Oromotor Stimulation for Transition from Gavage to Full Oral Feeding in Preterm Neonates: A Randomized controlled trial. AB - OBJECTIVE: To assess the effect of additional oromotor stimulation along with routine care on transition from gavage to full oral feeding in preterm neonates. METHODS: 51 neonates (28-34 weeks) randomized to receive either oromotor stimulation along with routine care (n=25, intervention), or routine care alone (n=26, control) (which included Kangaroo mother care and non-nutritive sucking). RESULTS: Median (IQR) days to reach partial and full spoon feed were significantly lesser [5(3-9.5) vs 10(5-15) P=0.006; and 7(5-14.5) vs 12.5(7-21); P=0.03] in intervention than in control group, respectively. A significantly higher number (56%) in intervention group as compared to control group (31%) achieved partial direct breast feeding at discharge (P=0.01). CONCLUSION: Oromotor stimulation along with routine care reduces the duration of gavage feeding in preterm neonates. PMID- 26840670 TI - Association Between Metabolic Control and Lipid Parameters in Indian Children with Type 1 Diabetes. AB - OBJECTIVE: To compare lipid parameters between diabetics and controls and to study association between metabolic control and lipid profile. METHODS: Lipid profile and HbA1c were measured (n=80, 39 boys) in diabetic children [age 10.7(3.4) y] and 54 controls, tests repeated after 1 year (in 45 diabetics). RESULTS: Diabetic children had higher mean (SD) LDL-C [95.3(27.7) vs 84.5(26.4) mg/dL], lower HDL-C [48.2 (13.1) vs 53.1(11.9) mg/dl]. Moderate physical activity (P=0.014) protected against high LDL-C levels. HbA1c (P=0.00) predicted total and LDL-C levels. At 1year, 63% showed reduced LDL-C with improving HbA1c; 72% showed increased LDL-C with deteriorated HbA1c. CONCLUSION: Improving metabolic control is cardinal to reduce cardiometabolic risk; physical activity is beneficial. PMID- 26840671 TI - Delayed Cutaneous Findings of Hand, Foot, and Mouth Disease. AB - OBJECTIVE: To describe various delayed cutaneous findings associated with hand, foot, and mouth disease (HFMD). METHODS: Patients presenting with clinical features of HFMD were followed-up prospectively for a period of 3 months for the occurrence of delayed cutaneous manifestations. RESULTS: Out of 68 patients on regular follow-up, 23 (33.8 %) showed different types of skin and nail changes following HFMD. Nineteen showed features of onychomadesis, 9 developed nail discoloration, and Beaus line was noted in 5 patients. Cutaneous desquamation was seen in 7 patients. Spontaneous re-growth of nails occurred in all cases within 12 weeks follow-up. Skin desquamation subsided by 2-4 weeks. CONCLUSION: Delayed cutaneous findings following HFMD are common. PMID- 26840672 TI - Why do we Write? PMID- 26840673 TI - Rapid Survey of Wasting and Stunting in Children: Whats New, Whats Old and Whats the Buzz? AB - Nationwide Rapid Survey on Children (RSoC), conducted by the Ministry of Women and Child Development and UNICEF in 2013-14 showed a marked improvement in the status of the child malnutrition over the third National Family Health Survey (NFHS-3) that was conducted in 2005-06. Despite some impressive gains in the anthropometric indicators of malnutrition, the absolute levels remain high, and of concern. Despite these gains, the feeding indicators remain stagnant. The programmatic responses need to adopt a multi-sectoral comprehensive approach with regular and comprehensive nutrition surveillance and recognize the epidemiological diversity. PMID- 26840675 TI - Urinary Tract Infection ,A Tale of 50 Years. PMID- 26840674 TI - An Adolescent with Kawasaki Disease. AB - Kawasaki disease is an acute vasculitis of unknown etiology that predominantly affects children <5 years of age. The incidence and the severity of myocarditis in this disease is variable and depends upon the stage of the disease, acute or chronic. Acute-stage Kawasaki disease shows relatively high incidence of myocarditis, but almost all cases are clinically mild. We describe teenage boy presenting with atypical/incomplete manifestations of Kawasaki disease and developing fulminant myocarditis within a week of illness resulting in death. The case underscores the importance of suspecting Kawasaki disease in a young child presenting with features of myocardial ischemia. PMID- 26840676 TI - Does Early Exposure to Animals Alter Risk of Childhood Asthma? PMID- 26840679 TI - A Tale of Two Worlds: From Head to Tail. PMID- 26840680 TI - Auxiliary Liver Transplantation for Acute Liver Failure. AB - BACKGROUND: Auxiliary partial orthotopic liver transplantation is a technique where part of diseased native liver is removed and replaced with healthy donor liver so that, the left behind native liver could later regenerate. CASE CHARACTERISTICS: 2 year 6 month old girl with acute liver failure due to Hepatitis A. She underwent a successful auxiliary partial orthotopic liver transplantation. OUTCOME: Successful native liver regeneration and immunosuppression withdrawal after two and half years of surgery. MESSAGE: In selective cases of acute liver failure, auxiliary partial orthotopic liver transplantation could provide a chance for native liver regeneration and immunosuppression-free life. PMID- 26840681 TI - Gastrointestinal Neuroendocrine Tumors in Two Children. AB - BACKGROUND: Enterochromaffin-like cell hyperplasia and neuroendocrine tumors are relatively rare in childhood. CASE CHARACTERISTICS: A 15-year-old girl who presented with epigastric pain and a 6-year-old boy who was admitted with hematochezia. Endoscopy revealed nodules in the stomach in Case 1, and polyploidy lesion in the rectum in Case 2. OUTCOME: Enterochromaffin-like cell hyperplasia in Case 1 and neuroendocrine tumor in Case 2. MESSAGE: A low index of suspicion for neuroendocrine tumors in children can result in delay in the detection of these rare but potentially malignant diseases. PMID- 26840682 TI - Poisoning by Polyethylene Glycol , An Adjuvant for Insecticides. AB - BACKGROUND: Accidental poisoning in children with surfactant used as an agriculture adjuvant is uncommon. CASE CHARACTERISTICS: A 7-month-old girl presented with severe respiratory distress 48 hours following ingestion of surfactant, and required intubation and mechanical ventilation. OUTCOME: The child was successfully managed with supportive therapy. MESSAGE: Poisoning by polyethylene glycol can be severe and life-threatening. PMID- 26840683 TI - Obesity in School Children: Methodological Issues. PMID- 26840684 TI - Obesity in School Children, Authors Reply. PMID- 26840685 TI - Exogenous Cushing Syndrome due to Topical Clobetasone use for Diaper Rash. PMID- 26840686 TI - Massive Idiopathic prepuberta Gigantomastial. PMID- 26840687 TI - When to Close Patent Ductus arteriosus, The Ideal Time and Rationale. PMID- 26840688 TI - When to Close Patent Ductus Arteriosus, Authors Reply. PMID- 26840689 TI - Kids and Floods. PMID- 26840690 TI - Hyperkinetic Movement Disorder in a Girl with Anti-NMDA Receptor Encephalitis. PMID- 26840691 TI - Pigmented Xerodermoid. PMID- 26840692 TI - Menkes Kinky Hair Disease. PMID- 26840693 TI - Caesarean Section in Peru: Analysis of Trends Using the Robson Classification System. AB - INTRODUCTION: Cesarean section rates continue to increase worldwide while the reasons appear to be multiple, complex and, in many cases, country specific. Over the last decades, several classification systems for caesarean section have been created and proposed to monitor and compare caesarean section rates in a standardized, reliable, consistent and action-oriented manner with the aim to understand the drivers and contributors of this trend. The aims of the present study were to conduct an analysis in the three Peruvian geographical regions to assess levels and trends of delivery by caesarean section using the Robson classification for caesarean section, identify the groups of women with highest caesarean section rates and assess variation of maternal and perinatal outcomes according to caesarean section levels in each group over time. MATERIAL AND METHODS: Data from 549,681 pregnant women included in the Peruvian Perinatal Information System database from 43 maternal facilities in three Peruvian geographical regions from 2000 and 2010 were studied. The data were analyzed using the Robson classification and women were studied in the ten groups in the classification. Cochran-Armitage test was used to evaluate time trends in the rates of caesarean section rates and; logistic regression was used to evaluate risk for each classification. RESULTS: The caesarean section rate was 27% and a yearly increase in the overall caesarean section rates from 2000 to 2010 from 23.5% to 30% (time trend p<0.001) was observed. Robson groups 1, 3 (nulliparous and multiparas, respectively, with a single cephalic term pregnancy in spontaneous labour), 5 (multiparas with a previous uterine scar with a single, cephalic, term pregnancy) and 7 (multiparas with a single breech pregnancy with or without previous scars) showed an increase in the caesarean section rates over time. Robson groups 1 and 3 were significantly associated with stillbirths (OR 1.43, CI95% 1.17-1.72; OR 3.53, CI95% 2.95-4.2) and maternal mortality (OR 3.39, CI95% 1.59-7.22; OR 8.05, CI95% 3.34-19.41). DISCUSSION: The caesarean section rates increased in the last years as result of increased CS in groups with spontaneous labor and in-group of multiparas with a scarred uterus. Women included in groups 1 y 3 were associated to maternal perinatal complications. Women with previous cesarean section constitute the most important determinant of overall cesarean section rates. The use of Robson classification becomes an useful tool for monitoring cesarean section in low human development index countries. PMID- 26840694 TI - Achieving sustained virologic response after interferon-free hepatitis C virus treatment correlates with hepatic interferon gene expression changes independent of cirrhosis. AB - Chronic hepatitis C virus (HCV) infection can now be treated with oral directly acting antiviral agents, either with or without ribavirin (RBV). Virologic relapse after treatment can occur, and in some studies was more common in cirrhotic subjects. We previously observed changes in hepatic immunity during interferon (IFN)-free therapy that correlated with favourable outcome in subjects with early liver disease. Here, we compared changes in endogenous IFN pathways during IFN-free, RBV-free therapy between cirrhotic and noncirrhotic subjects. mRNA and microRNA (miRNA) expression analyses were performed on paired pre- and post-treatment liver biopsies from genotype-1 HCV subjects treated with sofosbuvir/ledipasvir (SOF/LDV) for 12 weeks (n = 4, 3 cirrhotics) or SOF/LDV combined with GS-9669 or GS-9451 for 6 weeks (n = 6, 0 cirrhotics). Nine of ten subjects achieved a sustained virologic response (SVR), while one noncirrhotic subject relapsed. Hepatic IFN-stimulated gene expression decreased with treatment in the liver of all subjects, with no observable impact of cirrhosis. Hepatic gene expression of type III IFNs (IFNL1, IFNL3, IFNL4-DeltaG) similarly decreased with treatment, while IFNA2 expression, undetectable in all subjects pretreatment, was detected post-treatment in three subjects who achieved a SVR. Only the subject who relapsed had detectable IFNL4-DeltaG expression in post treatment liver. Other IFNs had no change in gene expression (IFNG, IFNB1, IFNA5) or could not be detected. Although expression of multiple hepatic miRNAs changed with treatment, many miRNAs previously implicated in HCV replication and IFN signalling had unchanged expression. In conclusion, favourable treatment outcome during IFN-free HCV therapy is associated with changes in the host IFN response regardless of cirrhosis. PMID- 26840696 TI - Adolescent Femoral Chondral Fragment Fixation With Poly-L-Lactic Acid Chondral Darts. AB - Large chondral injuries without attached bone are uncommon. This report describes a 14-year-old boy who had a unique stress reaction between the bone and the overlying cartilage, predominantly of the anterior lateral femoral condyle, during a week-long basketball camp, resulting in complete displacement of a 2.5 * 2.5-cm full-thickness articular cartilage lesion. There was a 6-day interval from the time of the injury to the first office appointment. Scheduling of magnetic resonance imaging and insurance approval took another week, and then surgery scheduling, including insurance approval and arranging for surgical supplies, took another week. Three weeks after the initial injury, the patient underwent diagnostic arthroscopy and open arthrotomy, and the cartilage-free fragment was returned to the donor site and fixed with poly-L-lactic acid chondral darts. Considerable delamination of the shoulders of the defect was noted on preoperative magnetic resonance imaging and at the time of surgery, suggesting an unusual prodromal stress reaction. Although there was no underlying subchondral bone on the free cartilage fragment, the injury healed. The patient had return of full knee range of motion and strength. Magnetic resonance imaging performed 3 months postoperatively showed healed cartilage. At 1 year of clinical follow-up, the patient had no clinical sequelae from the initial injury and had returned to competitive basketball. Prompt recognition of this injury pattern and subsequent surgical repair are necessary because the window of opportunity closes as fibrous healing occurs and the cartilage fragment deforms. The poly-L-lactic acid chondral dart system was instrumental to the success of this case. PMID- 26840695 TI - Clinical and Functional Outcomes of the Birmingham Hip Resurfacing System. AB - This study reported the outcomes of patients treated with the Birmingham Hip Resurfacing System (Smith & Nephew, Memphis, Tennessee) to identify the prevalence of complications and failures. A retrospective review of 202 patients (206 hips) was performed. Outcomes were assessed clinically with Harris Hip Score at 6 and 12 months and then yearly. Subanalysis was performed, with the hips divided according to patient sex and size of the femoral component. Mean patient age was 51+/-8 years, and mean follow-up was 4+/-1.6 years. Of the patients, 163 were men (83%) and 35 were women (17%). Postoperative improvement was significant, with preoperative Harris Hip Score of 62.9+/-10.6 and postoperative Harris Hip Score of 98.6+/-6.7 (P<.001). There were 9 patients (4%) who had complications. A total of 5 hips (2.4%) underwent revision. At 3 years, mean survival was better for men than for women (99% vs 92%, respectively). Survival was lowest in patients with femoral component diameter of less than 46 mm. According to the authors' results, the Birmingham Hip Resurfacing System resulted in good clinical outcomes at 4 years. Survival and outcomes in women, particularly those with modest bone size, are inferior. PMID- 26840697 TI - Removal of Well-Fixed Cementless Acetabular Components in Revision Total Hip Arthroplasty. AB - The Zimmer Explant Acetabular Cup Removal System (Warsaw, Indiana) has been touted as a superior method for removing well-fixed cementless acetabular components while minimizing bone loss; however, no comparative data support this. This study compares bone loss following the removal of well-fixed acetabular components with Aufranc gouges and with the Explant System. A review of 623 revision total hip arthroplasties (THAs) at the authors' institution between 2002 and 2013 identified cases involving the revision of well-fixed cementless hemispherical acetabular components for any reason except infection. Twenty-four cases using Aufranc gouges and 27 cases using the Explant System were included. The following surrogates for bone loss were used: (1) the difference between the initial acetabular component outer diameter (OD) and the final reamer OD; (2) the difference between the initial acetabular component OD and the new acetabular component OD; and (3) the use of impaction bone grafting. A 2-tailed Wilcoxon Mann-Whitney test was used to assess the difference in bone loss between the 2 groups. The use of bone grafting was compared between the groups with the chi square test. The median differences between the initial acetabular component and the final reamer (P=.004), as well as between the initial and new acetabular components (P=.002), were 2 mm less with the Explant System. Hips in the Aufranc group were more likely to have bone grafting (54% vs 26%; P=.04). These results suggest less bone loss when removing well-fixed acetabular components with the Zimmer Explant System compared with Aufranc gouges. PMID- 26840698 TI - Saphenous and Infrapatellar Nerves at the Adductor Canal: Anatomy and Implications in Regional Anesthesia. AB - Conflicting data exist regarding the anatomical relationship of the saphenous and infrapatellar nerves at the adductor canal and the location of the superior foramen of the canal. Therefore, the authors performed a cadaveric study to detail the relationship and course of the saphenous and infrapatellar nerves and the level of the superior foramen of the canal. The adductor canal and subsartorial compartment were dissected in 17 human cadavers. The distance between the superior foramen of the canal and the mid-distance (MD) between the base of the patella and the anterior superior iliac crest were measured; the course of the saphenous and infrapatellar nerves and the level of origin of the infrapatellar branch were detailed. In 13 of 17 specimens, the superior foramen of the adductor canal was distal to the MD (mean, 6.5 cm); in the remaining specimens, it was proximal to the MD. In 12 of 17 specimens, the infrapatellar branch exited the canal separately from the saphenous nerve; in the remaining specimens, it originated caudally to the canal. In all dissections, the infrapatellar branch had a constant course in close proximity to the saphenous nerve within the canal and between the sartorious muscle and femoral artery caudally to the canal. Most commonly, the superior foramen of the adductor canal is located caudally to the MD; the infrapatellar branch originates from the saphenous nerve within the canal and has a constant course in close proximity to the saphenous nerve. These observations should be considered for regional anesthesia techniques at the adductor canal. PMID- 26840699 TI - Paraspinal Muscle Atrophy After Lumbar Spine Surgery. AB - Paraspinal muscles are commonly affected during spine surgery. The purpose of this study was to assess the potential factors that contribute to paraspinal muscle atrophy (PMA) after lumbar spine surgery. A comprehensive review of the available English literature, including relevant abstracts and references of articles selected for review, was conducted to identify studies that reported PMA after spinal surgery. The amount of postoperative PMA was evaluated in (1) lumbar fusion vs nonfusion procedures; (2) posterior lumbar fusion vs anterior lumbar fusion; and (3) minimally invasive (MIS) posterior lumbar decompression and/or fusion vs non-MIS equivalent procedures. In total, 12 studies that included 529 patients (262 men and 267 women) were reviewed. Of these, 365 patients had lumbar fusions and 164 had lumbar decompressions. There was a significantly higher mean postoperative volumetric PMA with fusion vs nonfusion procedures (P=.0001), with posterior fusion vs anterior fusion (P=.0001), and with conventional fusions vs MIS fusions (P=.001). There was no significant difference in mean volumetric lumbar PMA with MIS decompression vs non-MIS decompression (P=.56). There was significantly higher postoperative PMA with lumbar spine fusions, posterior procedures, and non-MIS fusions. PMID- 26840700 TI - Distal Locking Screws for Intramedullary Nailing of Tibial Fractures. AB - Recently introduced tibial intramedullary nails allow a number of distal screws to be used to reduce the incidence of malalignment and loss of fixation of distal metaphyseal fractures. However, the number of screws and the type of screw configuration to be used remains obscure. This biomechanical study was performed to address this question. Thirty-six Expert tibial nails (Synthes, Oberdorf, Switzerland) were introduced in composite bone models. The models were divided into 4 groups with different distal locking configurations ranging from 2 to 4 screws. A 7-mm gap osteotomy was performed 72 mm from the tibial plafond to simulate a 42-C3 unstable distal tibial fracture. Each group was divided in 3 subgroups and underwent nondestructive biomechanical testing in axial compression, coronal bending, and axial torsion. The passive construct stiffness was measured and statistically analyzed with one-way analysis of variance. Although some differences were noted between the stiffness of each group, these were not statistically significant in compression (P=.105), bending (P=.801), external rotation (P=.246), and internal rotation (P=.370). This in vitro study showed that, when using the Expert tibial nail for unstable distal tibial fractures, the classic configuration of 2 parallel distal screws could provide the necessary stability under partial weight-bearing conditions. PMID- 26840701 TI - Transosseous Physeal-Sparing Rotator Cuff Repair in an Adolescent Football Player. AB - Rotator cuff injuries in the pediatric and adolescent population are rare. These injuries are normally caused by an acute event or by repeated microtrauma as a result of poor mechanics during overhead sporting activities. Overall, these injuries account for fewer than 1% of all rotator cuff tears. Physeal injuries, tuberosity avulsions ("rotator cuff equivalents"), and proximal humeral fractures commonly occur in the pediatric population. Traumatic full-thickness rotator cuff ruptures that occur in this age group during contact sports are an extremely uncommon cause of shoulder pain. The rarity of this type of injury in the pediatric and adolescent population may be the result of the excellent tensile properties of rotator tendons in childhood that often resist mechanical forces better than the growth plate or the apophyses. This report describes a full thickness rotator cuff tear and a posterior labral tear in a 12-year-old boy who had a direct injury to the shoulder while playing football. The authors' goal in reporting this case is to increase orthopedic surgeons' awareness of this type of injury. Early use of magnetic resonance imaging for persistent shoulder pain after direct injury during contact sports may avoid undue delay in diagnosis. This report also describes the mini-open transosseous extraphyseal technique of cuff repair and reviews the literature on this infrequent injury. Overall, excellent clinical outcomes and return to sports can be expected after surgical repair of torn and often retracted tendons. PMID- 26840702 TI - Ghrelin attenuates the growth of HO-8910 ovarian cancer cells through the ERK pathway. AB - Ovarian cancer is one of the most common causes of death from gynecologic tumors and is an important public health issue. Ghrelin is a recently discovered bioactive peptide that acts as a natural endogenous ligand of the growth hormone secretagogue receptor (GHSR). Several studies have identified the protective effects of ghrelin on the mammalian reproductive system. However, little research has been done on the effects of ghrelin on ovarian cancer cells, and the underlying mechanisms of these effects. We sought to understand the potential involvement of mitogen-activated protein kinases (MAPKs) in ghrelin-mediated inhibition of growth of the ovarian line HO-8910. We applied different concentrations of ghrelin and an inhibitor of the ghrelin receptor (D-Lys3-GHRP 6) to HO-8910 cells and observed the growth rate of cells and changes in phosphorylation of the MAPKs ERK1/2, JNK and p38. We discovered that ghrelin induced apoptosis of HO-8910 cells was though phosphorylated ERK1/2, and that this phosphorylation (as well as p90rsk phosphorylation) was mediated by the GHSR. The ERK1/2 pathway is known to play an essential part in the ghrelin mediated apoptosis of HO-8910 cells. Hence, our study suggests that ghrelin inhibits the growth of HO-8910 cells primarily through the GHSR/ERK pathway. PMID- 26840704 TI - Expression of BAFF and BR3 in patients with systemic lupus erythematosus. AB - The objective of this study was to examine the relationship between the expression of B cell activating factor (BAFF) and BAFF receptor in patients with disease activity of systemic lupus erythematosus (SLE). Real-time RT-PCR was used to examine BAFF mRNA expression in peripheral blood monocytes of active and stable SLE patients and healthy controls. The percentage of BAFF receptor 3 (BR3) on B lymphocytes was measured by flow cytometry. Soluble BAFF levels in serum were assayed by ELISA. Microalbumin levels were assayed by an automatic immune analysis machine. BAFF mRNA and soluble BAFF levels were highest in the active SLE group, followed by the stable SLE group, and controls (P<0.01). The percentage of BR3 on B lymphocytes was downregulated in the active SLE group compared with the stable SLE group and controls (P<0.01). BAFF mRNA levels and soluble BAFF levels were higher in patients who were positive for proteinuria than in those who were negative (P<0.01). The percentage of BR3 on B lymphocytes was lower in patients who were positive for proteinuria than in those who were negative (P<0.01). The BAFF/BR3 axis may be over-activated in SLE patients. BAFF and BR3 levels may be useful parameters for evaluating treatment. PMID- 26840703 TI - Effects of intracutaneous injections of sterile water in patients with acute low back pain: a randomized, controlled, clinical trial. AB - Intracutaneous sterile water injection (ISWI) is used for relief of low back pain during labor, acute attacks of urolithiasis, chronic neck and shoulder pain following whiplash injuries, and chronic myofascial pain syndrome. We conducted a randomized, double-blinded, placebo-controlled trial to evaluate the effect of ISWI for relief of acute low back pain (aLBP). A total of 68 patients (41 females and 27 males) between 18 and 55 years old experiencing aLBP with moderate to severe pain (scores >=5 on an 11-point visual analogue scale [VAS]) were recruited and randomly assigned to receive either ISWIs (n=34) or intracutaneous isotonic saline injections (placebo treatment; n=34). The primary outcome was improvement in pain intensity using the VAS at 10, 45, and 90 min and 1 day after treatment. The secondary outcome was functional improvement, which was assessed using the Patient-Specific Functional Scale (PSFS) 1 day after treatment. The mean VAS score was significantly lower in the ISWI group than in the control group at 10, 45, and 90 min, and 1 day after injection (P<0.05, t-test). The mean increment in PSFS score of the ISWI group was 2.9+/-2.2 1 day after treatment, while that in the control group was 0.9+/-2.2. Our study showed that ISWI was effective for relieving pain and improving function in aLBP patients at short term follow-up. ISWI might be an alternative treatment for aLBP patients, especially in areas where medications are not available, as well as in specific patients (e.g., those who are pregnant or have asthma), who are unable to receive medications or other forms of analgesia because of side effects. PMID- 26840705 TI - High-impact exercise in rats prior to and during suspension can prevent bone loss. AB - High-impact exercise has been considered an important method for treating bone loss in osteopenic experimental models. In this study, we investigated the effects of osteopenia caused by inactivity in femora and tibiae of rats subjected to jump training using the rat tail suspension model. Eight-week-old female Wistar rats were divided into five groups (n=10 each group): jump training for 2 weeks before suspension and training during 3 weeks of suspension; jump training for 2 weeks before suspension; jump training only during suspension; suspension without any training; and a control group. The exercise protocol consisted of 20 jumps/day, 5 days/week, with a jump height of 40 cm. The bone mineral density of the femora and tibiae was measured by double energy X-ray absorptiometry and the same bones were evaluated by mechanical tests. Bone microarchitecture was evaluated by scanning electron microscopy. One-way ANOVA was used to compare groups. Significance was determined as P<0.05. Regarding bone mineral density, mechanical properties and bone microarchitecture, the beneficial effects were greater in the bones of animals subjected to pre-suspension training and subsequently to training during suspension, compared with the bones of animals subjected to pre-suspension training or to training during suspension. Our results indicate that a period of high impact exercise prior to tail suspension in rats can prevent the installation of osteopenia if there is also training during the tail suspension. PMID- 26840706 TI - Correlation between heart rate variability and pulmonary function adjusted by confounding factors in healthy adults. AB - The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincare plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders. PMID- 26840708 TI - Analysis of fracture healing in osteopenic bone caused by disuse: experimental study. AB - Osteoporosis has become a serious global public health issue. Hence, osteoporotic fracture healing has been investigated in several previous studies because there is still controversy over the effect osteoporosis has on the healing process. The current study aimed to analyze two different periods of bone healing in normal and osteopenic rats. Sixty, 7-week-old female Wistar rats were randomly divided into four groups: unrestricted and immobilized for 2 weeks after osteotomy (OU2), suspended and immobilized for 2 weeks after osteotomy (OS2), unrestricted and immobilized for 6 weeks after osteotomy (OU6), and suspended and immobilized for 6 weeks after osteotomy (OS6). Osteotomy was performed in the middle third of the right tibia 21 days after tail suspension, when the osteopenic condition was already set. The fractured limb was then immobilized by orthosis. Tibias were collected 2 and 6 weeks after osteotomy, and were analyzed by bone densitometry, mechanical testing, and histomorphometry. Bone mineral density values from bony calluses were significantly lower in the 2-week post-osteotomy groups compared with the 6-week post-osteotomy groups (multivariate general linear model analysis, P<0.000). Similarly, the mechanical properties showed that animals had stronger bones 6 weeks after osteotomy compared with 2 weeks after osteotomy (multivariate general linear model analysis, P<0.000). Histomorphometry indicated gradual bone healing. Results showed that osteopenia did not influence the bone healing process, and that time was an independent determinant factor regardless of whether the fracture was osteopenic. This suggests that the body is able to compensate for the negative effects of suspension. PMID- 26840707 TI - Combined treatment with caffeic and ferulic acid from Baccharis uncinella C. DC. (Asteraceae) protects against metabolic syndrome in mice. AB - Fractionation of the EtOH extract from aerial parts of Baccharis uncinella C. DC. (Asteraceae) led to isolation of caffeic and ferulic acids, which were identified from spectroscopic and spectrometric evidence. These compounds exhibit antioxidant and anti-inflammatory properties and have been shown to be effective in the prevention/treatment of metabolic syndrome. This study investigated whether the combined treatment of caffeic and ferulic acids exhibits a more significant beneficial effect in a mouse model with metabolic syndrome. The combination treatment with caffeic and ferulic acids was tested for 60 days in C57 mice kept on a high-fat (40%) diet. The data obtained indicated that treatment with caffeic and ferulic acids prevented gain in body weight induced by the high-fat diet and improved hyperglycemia, hypercholesterolemia and hypertriglyceridemia. The expression of a number of metabolically relevant genes was affected in the liver of these animals, showing that caffeic and ferulic acid treatment results in increased cholesterol uptake and reduced hepatic triglyceride synthesis in the liver, which is a likely explanation for the prevention of hepatic steatosis. In conclusion, the combined treatment of caffeic and ferulic acids displayed major positive effects towards prevention of multiple aspects of the metabolic syndrome and liver steatosis in an obese mouse model. PMID- 26840709 TI - Gene expression profiling analysis of lung adenocarcinoma. AB - The present study screened potential genes related to lung adenocarcinoma, with the aim of further understanding disease pathogenesis. The GSE2514 dataset including 20 lung adenocarcinoma and 19 adjacent normal tissue samples from 10 patients with lung adenocarcinoma aged 45-73 years was downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) between the two groups were screened using the t-test. Potential gene functions were predicted using functional and pathway enrichment analysis, and protein-protein interaction (PPI) networks obtained from the STRING database were constructed with Cytoscape. Module analysis of PPI networks was performed through MCODE in Cytoscape. In total, 535 upregulated and 465 downregulated DEGs were identified. These included ATP5D, UQCRC2, UQCR11 and genes encoding nicotinamide adenine dinucleotide (NADH), which are mainly associated with mitochondrial ATP synthesis coupled electron transport, and which were enriched in the oxidative phosphorylation pathway. Other DEGs were associated with DNA replication (PRIM1, MCM3, and RNASEH2A), cell surface receptor-linked signal transduction and the enzyme-linked receptor protein signaling pathway (MAPK1, STAT3, RAF1, and JAK1), and regulation of the cytoskeleton and phosphatidylinositol signaling system (PIP5K1B, PIP5K1C, and PIP4K2B). Our findings suggest that DEGs encoding subunits of NADH, PRIM1, MCM3, MAPK1, STAT3, RAF1, and JAK1 might be associated with the development of lung adenocarcinoma. PMID- 26840710 TI - Risk factors for pulmonary hypertension in patients receiving maintenance peritoneal dialysis. AB - We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43+/-8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the chi2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH. PMID- 26840711 TI - Contact force-guided catheter ablation for the treatment of atrial fibrillation: a meta-analysis of randomized, controlled trials. AB - Contact force (CF) sensing technology allows real-time monitoring during catheter ablation for atrial fibrillation (AF). However, the effect of CF sensing technology on procedural parameters and clinical outcomes still needs clarification. Because of the inconsistent results thus far in this area, we performed a meta-analysis to determine whether CF sensing technology can improve procedural parameters and clinical outcomes for the treatment of AF. Studies examining the benefits of CF sensing technology were identified in English language articles by searching the MEDLINE, Web of Science, and Cochrane Library databases (inception to May 2015). Ten randomized, controlled trials involving 1834 patients (1263 males, 571 females) were included in the meta-analysis (681 in the CF group, 1153 in the control group). Overall, the ablation time was significantly decreased by 7.34 min (95%CI=-12.21 to -2.46; P=0.003, Z test) in the CF group compared with the control group. CF sensing technology was associated with significantly improved freedom from AF after 12 months (OR=1.55, 95%CI=1.20 to 1.99; P=0.0007) and complications were significantly lower in the CF group than in the control group (OR=0.50, 95%CI=0.29 to 0.87; P=0.01). However, fluoroscopy time analysis showed no significantly decreased trend associated with CF-guided catheter ablation (weighted mean difference: -2.59; 95%CI=-9.06 to 3.88; P=0.43). The present meta-analysis shows improvement in ablation time and freedom from AF after 12 months in AF patients treated with CF guided catheter ablation. However, CF-guided catheter ablation does not decrease fluoroscopy time. PMID- 26840712 TI - Prevalence of child malnutrition at a university hospital using the World Health Organization criteria and bioelectrical impedance data. AB - Malnutrition constitutes a major public health concern worldwide and serves as an indicator of hospitalized patients' prognosis. Although various methods with which to conduct nutritional assessments exist, large hospitals seldom employ them to diagnose malnutrition. The aim of this study was to understand the prevalence of child malnutrition at the University Hospital of the Ribeirao Preto Medical School, University of Sao, Brazil. A cross-sectional descriptive study was conducted to compare the nutritional status of 292 hospitalized children with that of a healthy control group (n=234). Information regarding patients' weight, height, and bioelectrical impedance (i.e., bioelectrical impedance vector analysis) was obtained, and the phase angle was calculated. Using the World Health Organization (WHO) criteria, 35.27% of the patients presented with malnutrition; specifically, 16.10% had undernutrition and 19.17% were overweight. Classification according to the bioelectrical impedance results of nutritional status was more sensitive than the WHO criteria: of the 55.45% of patients with malnutrition, 51.25% exhibited undernutrition and 4.20% were overweight. After applying the WHO criteria in the unpaired control group (n=234), we observed that 100.00% of the subjects were eutrophic; however, 23.34% of the controls were malnourished according to impedance analysis. The phase angle was significantly lower in the hospitalized group than in the control group (P<0.05). Therefore, this study suggests that a protocol to obtain patients' weight and height must be followed, and bioimpedance data must be examined upon hospital admission of all children. PMID- 26840713 TI - Clinical and pathological challenges in the diagnosis of late-onset biliary atresia: four case studies. AB - Biliary atresia (BA) is classically described at the neonatal age. However, rare cases of BA in older infants have also been reported. We report four cases of late-onset BA in infants older than 4 weeks (3 males, 1 female), and describe the diagnostic and management difficulties. One of the cases had a late-onset (29 weeks) presentation with a successful surgical procedure. We highlight the importance of this unusual differential diagnosis in infants with cholestatic syndrome, who may benefit from Kasai surgery, regardless of age. PMID- 26840714 TI - Effect of selective beta-adrenoceptor blockade and surgical resection of the celiac-superior mesenteric ganglion complex on delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats. AB - There is evidence for participation of peripheral beta-adrenoceptors in delayed liquid gastric emptying (GE) induced in rats by dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At). The present study aimed to determine whether beta adrenoceptors are involved in delayed GE induced by phenylpyrazole derivatives and the role of the prevertebral sympathetic nervous system in this condition. Male Wistar rats weighing 220-280 g were used in the study. In the first experiment rats were intravenously pretreated with vehicle (V), atenolol 30 mg/kg (ATE, beta1-adrenergic antagonist), or butoxamine 25 mg/kg (BUT, beta2-adrenergic antagonist). In the second experiment, rats were pretreated with V or SR59230A 2 mg/kg (SRA, beta3-adrenergic antagonist). In the third experiment, rats were subjected to surgical resection of the celiac-superior mesenteric ganglion complex or to sham surgery. The groups were intravenously treated with saline (S), 240 umol/kg Dp, AA, or At, 15 min after pretreatment with the antagonists or V and nine days after surgery. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. The %GR (means+/-SE, n=6) values indicated that BUT abolished the effect of Dp (BUT+Dp vs V+Dp: 35.0%+/-5.1% vs 56.4%+/-2.7%) and At (BUT+At vs V+At: 33.5%+/-4.7% vs 52.9%+/-2.6%) on GE, and significantly reduced (P<0.05) the effect of AA (BUT+AA vs V+AA: 48.0%+/-5.0% vs 65.2%+/-3.8%). ATE, SRA, and sympathectomy did not modify the effects of treatments. These results suggest that beta2-adrenoceptor activation occurred in delayed liquid gastric emptying induced by the phenylpyrazole derivatives dipyrone, 4-aminoantipyrine, and antipyrine. Additionally, the released neurotransmitter did not originate in the celiac-superior mesenteric ganglion complex. PMID- 26840716 TI - CD33(+) /HLA-DR(neg) and CD33(+) /HLA-DR(+/-) Cells: Rare Populations in the Human Decidua with Characteristics of MDSC. AB - PROBLEM: Human pregnancy needs a remarkable local immune tolerance toward the conceptus. Myeloid-derived suppressor cells (MDSC) are important players promoting cancer initiation and progression by suppressing T-cell functions and thus inducing immune tolerance. Therefore, MDSC were expected within decidua. METHODS: Subpopulations of CD33(+) immune cells were isolated from human early pregnancy decidua and characterized phenotypically and functionally by microscopy, FACS analysis, RT-PCR, Western blotting and in the coculture with T cells. RESULTS: Decidua harbors CD33(+) /HLA-DR(neg) and CD33(+) /HLA-DR(+/-) cells which both express arginase, iNOS and IDO and a typical cytokine profile. Both subtypes potently suppress T-cell proliferation and therefore fulfill the criteria of MDSC. CONCLUSION: We characterized a new population of CD33(+) /HLA DR(neg) and CD33(+) /HLA-DR(+/-) cells in human early pregnancy decidua with properties of classical MDSC and thus potentially being an important player in immune tolerance in pregnancy. PMID- 26840717 TI - Finally, We Can Relax: A New Generation of Muscle Models that Incorporate Sarcomere Compliance. PMID- 26840715 TI - Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure. AB - Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H) and 8 normotensive (N) subjects (age: 46.5+/-1.3 and 45.6+/ 1.4 years old, body mass index: 25.8+/-0.8 and 25.6+/-0.6 kg/m2, mean arterial pressure: 98.0+/-2.8 and 86.0+/-2.3 mmHg, respectively). They remained at rest in a sitting position for 10 min in a thermoneutral environment (22 degrees C) followed by 30 min in a heated environmental chamber (38 degrees C and 60% relative humidity). Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS) levels and ferric reducing ability of plasma (FRAP). Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05), although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1) and lower TBARS (P<0.01) and FRAP (P<0.05) levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors), present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response. PMID- 26840718 TI - SpringSaLaD: A Spatial, Particle-Based Biochemical Simulation Platform with Excluded Volume. AB - We introduce Springs, Sites, and Langevin Dynamics (SpringSaLaD), a comprehensive software platform for spatial, stochastic, particle-based modeling of biochemical systems. SpringSaLaD models biomolecules in a coarse-grained manner as a group of linked spherical sites with excluded volume. This mesoscopic approach bridges the gap between highly detailed molecular dynamics simulations and the various methods used to study network kinetics and diffusion at the cellular level. SpringSaLaD is a standalone tool that supports model building, simulation, visualization, and data analysis, all through a user-friendly graphical user interface that should make it more accessible than tools built into more comprehensive molecular dynamics infrastructures. Importantly, for bimolecular reactions we derive an exact expression relating the macroscopic on-rate to the various microscopic parameters with the inclusion of excluded volume; this makes SpringSaLaD more accurate than other tools, which rely on approximate relationships between these parameters. PMID- 26840719 TI - DNA Shape versus Sequence Variations in the Protein Binding Process. AB - The binding process of a protein with a DNA involves three stages: approach, encounter, and association. It has been known that the complexation of protein and DNA involves mutual conformational changes, especially for a specific sequence association. However, it is still unclear how the conformation and the information in the DNA sequences affects the binding process. What is the extent to which the DNA structure adopted in the complex is induced by protein binding, or is instead intrinsic to the DNA sequence? In this study, we used the multiscale simulation method to explore the binding process of a protein with DNA in terms of DNA sequence, conformation, and interactions. We found that in the approach stage the protein can bind both the major and minor groove of the DNA, but uses different features to locate the binding site. The intrinsic conformational properties of the DNA play a significant role in this binding stage. By comparing the specific DNA with the nonspecific in unbound, intermediate, and associated states, we found that for a specific DNA sequence, ~40% of the bending in the association forms is intrinsic and that ~60% is induced by the protein. The protein does not induce appreciable bending of nonspecific DNA. In addition, we proposed that the DNA shape variations induced by protein binding are required in the early stage of the binding process, so that the protein is able to approach, encounter, and form an intermediate at the correct site on DNA. PMID- 26840720 TI - Shear-Induced Unfolding and Enzymatic Cleavage of Full-Length VWF Multimers. AB - Proteolysis of the multimeric blood coagulation protein von Willebrand Factor (VWF) by ADAMTS13 is crucial for prevention of microvascular thrombosis. ADAMTS13 cleaves VWF within the mechanosensitive A2 domain, which is believed to open under shear flow. In this study, we combine fluorescence correlation spectroscopy (FCS) and a microfluidic shear cell to monitor real-time kinetics of full-length VWF proteolysis as a function of shear stress. For comparison, we also measure the Michaelis-Menten kinetics of ADAMTS13 cleavage of wild-type VWF in the absence of shear but partially denaturing conditions. Under shear, ADAMTS13 activity on full-length VWF arises without denaturing agent as evidenced by FCS and gel-based multimer analysis. In agreement with Brownian hydrodynamics simulations, we find a sigmoidal increase of the enzymatic rate as a function of shear at a threshold shear rate gamma1/2 = 5522/s. The same flow-rate dependence of ADAMTS13 activity we also observe in blood plasma, which is relevant to predict hemostatic dysfunction. PMID- 26840721 TI - Automated Ex Situ Assays of Amyloid Formation on a Microfluidic Platform. AB - Increasingly prevalent neurodegenerative diseases are associated with the formation of nanoscale amyloid aggregates from normally soluble peptides and proteins. A widely used strategy for following the aggregation process and defining its kinetics involves the use of extrinsic dyes that undergo a spectral shift when bound to beta-sheet-rich aggregates. An attractive route to carry out such studies is to perform ex situ assays, where the dye molecules are not present in the reaction mixture, but instead are only introduced into aliquots taken from the reaction at regular time intervals to avoid the possibility that the dye molecules interfere with the aggregation process. However, such ex situ measurements are time-consuming to perform, require large sample volumes, and do not provide for real-time observation of aggregation phenomena. To overcome these limitations, here we have designed and fabricated microfluidic devices that offer continuous and automated real-time ex situ tracking of the protein aggregation process. This device allows us to improve the time resolution of ex situ aggregation assays relative to conventional assays by more than one order of magnitude. The availability of an automated system for tracking the progress of protein aggregation reactions without the presence of marker molecules in the reaction mixtures opens up the possibility of routine noninvasive study of protein aggregation phenomena. PMID- 26840722 TI - Spin Densities in Flavin Analogs within a Flavoprotein. AB - Characterization by electron paramagnetic resonance techniques of several variants of Anabaena flavodoxin, where the naturally occurring FMN cofactor is substituted by different analogs, makes it possible to improve the details of the spin distribution map in the isoallosazine ring in its semiquinone state. The analyzed variants were selected to monitor the effects of intrinsic changes in the flavin ring electronic structure, as well as perturbations in the apoflavodoxin-flavin interaction, on the spin populations. When these effects were analyzed together with the functional properties of the different flavodoxin variants, a relationship between spin population and biochemical parameters, as the reduction potential, could be envisaged. PMID- 26840724 TI - Computational Studies of Molecular Permeation through Connexin26 Channels. AB - A signal property of connexin channels is the ability to mediate selective diffusive movement of molecules through plasma membrane(s), but the energetics and determinants of molecular movement through these channels have yet to be understood. Different connexin channels have distinct molecular selectivities that cannot be explained simply on the basis of size or charge of the permeants. To gain insight into the forces and interactions that underlie selective molecular permeation, we investigated the energetics of two uncharged derivatized sugars, one permeable and one impermeable, through a validated connexin26 (Cx26) channel structural model, using molecular dynamics and associated analytic tools. The system is a Cx26 channel equilibrated in explicit membrane/solvent, shown by Brownian dynamics to reproduce key conductance characteristics of the native channel. The results are consistent with the known difference in permeability to each molecule. The energetic barriers extend through most of the pore length, rather than being highly localized as in ion-specific channels. There is little evidence for binding within the pore. Force decomposition reveals how, for each tested molecule, interactions with water and the Cx26 protein vary over the length of the pore and reveals a significant contribution from hydrogen bonding and interaction with K(+). The flexibility of the pore width varies along its length, and the tested molecules have differential effects on pore width as they pass through. Potential sites of interaction within the pore are defined for each molecule. The results suggest that for the tested molecules, differences in hydrogen bonding and entropic factors arising from permeant flexibility substantially contribute to the energetics of permeation. This work highlights factors involved in selective molecular permeation that differ from those that define selectivity among atomic ions. PMID- 26840723 TI - Early Folding Events, Local Interactions, and Conservation of Protein Backbone Rigidity. AB - Protein folding is in its early stages largely determined by the protein sequence and complex local interactions between amino acids, resulting in lower energy conformations that provide the context for further folding into the native state. We compiled a comprehensive data set of early folding residues based on pulsed labeling hydrogen deuterium exchange experiments. These early folding residues have corresponding higher backbone rigidity as predicted by DynaMine from sequence, an effect also present when accounting for the secondary structures in the folded protein. We then show that the amino acids involved in early folding events are not more conserved than others, but rather, early folding fragments and the secondary structure elements they are part of show a clear trend toward conserving a rigid backbone. We therefore propose that backbone rigidity is a fundamental physical feature conserved by proteins that can provide important insights into their folding mechanisms and stability. PMID- 26840725 TI - Role of Electroosmosis in the Permeation of Neutral Molecules: CymA and Cyclodextrin as an Example. AB - To quantify the flow of small uncharged molecules into and across nanopores, one often uses ion currents. The respective ion-current fluctuations caused by the presence of the analyte make it possible to draw some conclusions about the direction and magnitude of the analyte flow. However, often this flow appears to be asymmetric with respect to the applied voltage. As a possible reason for this asymmetry, we identified the electroosmotic flow (EOF), which is the water transport associated with ions driven by the external transmembrane voltage. As an example, we quantify the contribution of the EOF through a nanopore by investigating the permeation of alpha-cyclodextrin through CymA, a cyclodextrin specific channel from Klebsiella oxytoca. To understand the results from electrophysiology on a molecular level, all-atom molecular dynamics simulations are used to detail the effect of the EOF on substrate entry to and exit from a CymA channel in which the N-terminus has been deleted. The combined experimental and computational results strongly suggest that one needs to account for the significant contribution of the EOF when analyzing the penetration of cyclodextrins through the CymA pore. This example study at the same time points to the more general finding that the EOF needs to be considered in translocation studies of neutral molecules and, at least in many cases, should be able to help in discriminating between translocation and binding events. PMID- 26840726 TI - Glucosylceramide Reorganizes Cholesterol-Containing Domains in a Fluid Phospholipid Membrane. AB - Glucosylceramide (GlcCer), one of the simplest glycosphingolipids, plays key roles in physiology and pathophysiology. It has been suggested that GlcCer modulates cellular events by forming specialized domains. In this study, we investigated the interplay between GlcCer and cholesterol (Chol), an important lipid involved in the formation of liquid-ordered (lo) phases. Using fluorescence microscopy and spectroscopy, and dynamic and electrophoretic light scattering, we characterized the interaction between these lipids in different pH environments. A quantitative description of the phase behavior of the ternary unsaturated phospholipid/Chol/GlcCer mixture is presented. The results demonstrate coexistence between lo and liquid-disordered (ld) phases. However, the extent of lo/ld phase separation is sparse, mainly due to the ability of GlcCer to segregate into tightly packed gel domains. As a result, the phase diagram of these mixtures is characterized by an extensive three-phase coexistence region of fluid (ld-phospholipid enriched)/lo (Chol enriched)/gel (GlcCer enriched). Moreover, the results show that upon acidification, GlcCer solubility in the lo phase is increased, leading to a larger lo/ld coexistence region. Quantitative analyses allowed us to determine the differences in the composition of the phases at neutral and acidic pH. These results predict the impact of GlcCer on domain formation and membrane organization in complex biological membranes, and provide a background for unraveling the relationship between the biophysical properties of GlcCer and its biological action. PMID- 26840727 TI - Netrin-1-Regulated Distribution of UNC5B and DCC in Live Cells Revealed by TICCS. AB - Netrins are secreted proteins that direct cell migration and adhesion during development. Netrin-1 binds its receptors deleted in colorectal cancer (DCC) and the UNC5 homologs (UNC5A-D) to activate downstream signaling that ultimately directs cytoskeletal reorganization. To investigate how netrin-1 regulates the dynamic distribution of DCC and UNC5 homologs, we applied fluorescence confocal and total internal reflection fluorescence microscopy, and sliding window temporal image cross correlation spectroscopy, to measure time profiles of the plasma membrane distribution, aggregation state, and interaction fractions of fluorescently tagged netrin receptors expressed in HEK293T cells. Our measurements reveal changes in receptor aggregation that are consistent with netrin-1-induced recruitment of DCC-enhanced green fluorescent protein (EGFP) from intracellular vesicles to the plasma membrane. Netrin-1 also induced colocalization of coexpressed full-length DCC-EGFP with DCC-T-mCherry, a putative DCC dominant negative that replaces the DCC intracellular domain with mCherry, consistent with netrin-1-induced receptor oligomerization, but with no change in aggregation state with time, providing evidence that signaling via the DCC intracellular domain triggers DCC recruitment to the plasma membrane. UNC5B expressed alone was also recruited by netrin-1 to the plasma membrane. Coexpressed DCC and UNC5 homologs are proposed to form a heteromeric netrin receptor complex to mediate a chemorepellent response. Application of temporal image cross correlation spectroscopy to image series of cells coexpressing UNC5B mCherry and DCC-EGFP revealed a netrin-1-induced increase in colocalization, with both receptors recruited to the plasma membrane from preexisting clusters, consistent with vesicular recruitment and receptor heterooligomerization. Plasma membrane recruitment of DCC or UNC5B was blocked by application of the netrin-1 VI-V peptide, which fails to activate chemoattraction, or by pharmacological block of Src family kinase signaling, consistent with receptor recruitment requiring netrin-1-activated signaling. Our findings reveal a mechanism activated by netrin-1 that recruits DCC and UNC5B to the plasma membrane. PMID- 26840729 TI - Principles Governing the Self-Assembly of Coiled-Coil Protein Nanoparticles. AB - Self-assembly refers to the spontaneous organization of individual building blocks into higher order structures. It occurs in biological systems such as spherical viruses, which utilize icosahedral symmetry as a guiding principle for the assembly of coat proteins into a capsid shell. In this study, we characterize the self-assembling protein nanoparticle (SAPN) system, which was inspired by such viruses. To facilitate self-assembly, monomeric building blocks have been designed to contain two oligomerization domains. An N-terminal pentameric coiled coil domain is linked to a C-terminal coiled-coil trimer by two glycine residues. By combining monomers with inherent propensity to form five- and threefold symmetries in higher order agglomerates, the supposition is that nanoparticles will form that exhibit local and global symmetry axes of order 3 and 5. This article explores the principles that govern the assembly of such a system. Specifically, we show that the system predominantly forms according to a spherical core-shell morphology using a combination of scanning transmission electron microscopy and small angle neutron scattering. We introduce a mathematical toolkit to provide a specific description of the possible SAPN morphologies, and we apply it to characterize all particles with maximal symmetry. In particular, we present schematics that define the relative positions of all individual chains in the symmetric SAPN particles, and provide a guide of how this approach can be generalized to nonspherical morphologies, hence providing unprecedented insights into their geometries that can be exploited in future applications. PMID- 26840730 TI - Compliance Accelerates Relaxation in Muscle by Allowing Myosin Heads to Move Relative to Actin. AB - The mechanisms that limit the speed at which striated muscles relax are poorly understood. This work presents, to our knowledge, novel simulations that show that the time course of relaxation is accelerated by interfilamentary movement resulting from series compliance; force drops faster when myosin heads move relative to actin during relaxation. This insight was obtained by using cross bridge distribution techniques to simulate the mechanical behavior of half sarcomeres that were connected in series with springs of varying stiffness. (The springs mimic the combined effects of half-sarcomere heterogeneity and muscle's series elastic component.) Half-sarcomeres that shortened by >~10 nm when they were activated subsequently relaxed with a biphasic profile; force initially declined slowly and approximately linearly before collapsing with a fast exponential time course. Stretches imposed during the linear phase quickened relaxation, while shortening movements prolonged the time course. These predictions are consistent with data from experiments performed by many other groups using single muscle fibers and isolated myofibrils. When half-sarcomeres were linked to stiff springs (so that they did not shorten appreciably during the simulations), force relaxed with a slow exponential time course and did not show biphasic behavior. Together, these results suggest that fast relaxation of striated muscle is an emergent property that reflects multiscale interactions within the muscle architecture. The nonlinear behavior during relaxation reflects perturbations to the dynamic coupling of regulated binding sites and cycling myosin heads that are induced by interfilamentary movement. PMID- 26840728 TI - Depletion with Cyclodextrin Reveals Two Populations of Cholesterol in Model Lipid Membranes. AB - Recent results provide evidence that cholesterol is highly accessible for removal from both cell and model membranes above a threshold concentration that varies with membrane composition. Here we measured the rate at which methyl-beta cyclodextrin depletes cholesterol from a supported lipid bilayer as a function of cholesterol mole fraction. We formed supported bilayers from two-component mixtures of cholesterol and a PC (phosphatidylcholine) lipid, and we directly visualized the rate of decrease in area of the bilayers with fluorescence microscopy. Our technique yields the accessibility of cholesterol over a wide range of concentrations (30-66 mol %) for many individual bilayers, enabling fast acquisition of replicate data. We found that the bilayers contain two populations of cholesterol, one with low surface accessibility and the other with high accessibility. A larger fraction of the total membrane cholesterol appears in the more accessible population when the acyl chains of the PC-lipid tails are more unsaturated. Our findings are most consistent with the predictions of the condensed-complex and cholesterol bilayer domain models of cholesterol phospholipid interactions in lipid membranes. PMID- 26840731 TI - Real-Time Monitoring of Platelet Activation Using Quartz Thickness-Shear Mode Resonator Sensors. AB - In this study, quartz thickness-shear mode (TSM) resonator sensors were adopted to monitor the process of platelet activation. Resting platelets adhering to fibrinogen-coated electrodes were activated by different concentrations of thrombin (1, 10, and 100 U/mL), and the corresponding electrical admittance spectra of TSM resonators during this process were recorded. Based on a bilayer loading transmission line model of TSM resonators, the complex shear modulus (G' + jG") and the average thickness (hPL) of the platelet monolayer at a series of time points were obtained. Decrease in thrombin concentration from 100 to 1 U/mL shifted all peaks and plateaus in G', G", and hPL to higher time points, which could be attributed to the partial activation of platelets by low concentrations of thrombin. The peak value of hPL was acquired when platelets presented their typical spherical shape as the first transformation in activation process. The G' peak appeared 10 ~ 20 min after hPL peak, when some filopods were observed along the periphery of platelets but without obvious cell spreading. As platelet spreading began and continued, G', G", and hPL decreased, leading to a steady rise of resonance frequency shift of TSM resonator sensors. The results show high reliability and stability of TSM resonator sensors in monitoring the process of platelet activation, revealing an effective method to measure platelet activities in real-time under multiple experimental conditions. The G', G", and hPL values could provide useful quantitative measures on platelet structure variations in activation process, indicating potential of TSM resonators in characterization of cells during their transformation. PMID- 26840732 TI - X-Ray Micro- and Nanodiffraction Imaging on Human Mesenchymal Stem Cells and Differentiated Cells. AB - Adult human mesenchymal stem cells show structural rearrangements of their cytoskeletal network during mechanically induced differentiation toward various cell types. In particular, the alignment of acto-myosin fibers is cell fate dependent and can serve as an early morphological marker of differentiation. Quantification of such nanostructures on a mesoscopic scale requires high resolution imaging techniques. Here, we use small- angle x-ray scattering with a spot size in the micro- and submicrometer range as a high-resolution and label free imaging technique to reveal structural details of stem cells and differentiated cell types. We include principal component analysis into an automated empirical analysis scheme that allows the local characterization of oriented structures. Results on freeze-dried samples lead to quantitative structural information for all cell lines tested: differentiated cells reveal pronounced structural orientation and a relatively intense overall diffraction signal, whereas naive human mesenchymal stem cells lack these features. Our data support the hypothesis of stem cells establishing ordered structures along their differentiation process. PMID- 26840733 TI - Phase Analysis of Metabolic Oscillations and Membrane Potential in Pancreatic Islet beta-Cells. AB - Metabolism in islet beta-cells displays oscillations that can trigger pulses of electrical activity and insulin secretion. There has been a decades-long debate among islet biologists about whether metabolic oscillations are intrinsic or occur in response to oscillations in intracellular Ca(2+) that result from bursting electrical activity. In this article, the dynamics of oscillatory metabolism were investigated using five different optical reporters. Reporter activity was measured simultaneously with membrane potential bursting to determine the phase relationships between the metabolic oscillations and electrical activity. Our experimental findings suggest that Ca(2+) entry into beta-cells stimulates the rate of mitochondrial metabolism, accounting for the depletion of glycolytic intermediates during each oscillatory burst. We also performed Ca(2+) clamp tests in which we clamped membrane potential with the KATP channel-opener diazoxide and KCl to fix Ca(2+) at an elevated level. These tests confirm that metabolic oscillations do not require Ca(2+) oscillations, but show that Ca(2+) plays a larger role in shaping metabolic oscillations than previously suspected. A dynamical picture of the mechanisms of oscillations emerged that requires the restructuring of contemporary mathematical beta-cell models, including our own dual oscillator model. In the companion article, we modified our model to account for these new data. PMID- 26840734 TI - Disentangling Random Motion and Flow in a Complex Medium. AB - We describe a technique for deconvolving the stochastic motion of particles from large-scale fluid flow in a dynamic environment such as that found in living cells. The method leverages the separation of timescales to subtract out the persistent component of motion from single-particle trajectories. The mean squared displacement of the resulting trajectories is rescaled so as to enable robust extraction of the diffusion coefficient and subdiffusive scaling exponent of the stochastic motion. We demonstrate the applicability of the method for characterizing both diffusive and fractional Brownian motion overlaid by flow and analytically calculate the accuracy of the method in different parameter regimes. This technique is employed to analyze the motion of lysosomes in motile neutrophil-like cells, showing that the cytoplasm of these cells behaves as a viscous fluid at the timescales examined. PMID- 26840735 TI - Cell Fate Specification Based on Tristability in the Inner Cell Mass of Mouse Blastocysts. AB - During development, interactions between transcription factors control the specification of different cell fates. The regulatory networks of genetic interactions often exhibit multiple stable steady states; such multistability provides a common dynamical basis for differentiation. During early murine embryogenesis, cells from the inner cell mass (ICM) can be specified in epiblast (Epi) or primitive endoderm (PrE). Besides the intracellular gene regulatory network, specification is also controlled by intercellular interactions involving Erk signaling through extracellular Fgf4. We previously proposed a model that describes the gene regulatory network and its interaction with Erk signaling in ICM cells. The model displays tristability in a range of Fgf4 concentrations and accounts for the self-organized specification process observed in vivo. Here, we further investigate the origin of tristability in the model and analyze in more detail the specification process by resorting to a simplified two-cell model. We also carry out simulations of a population of 25 cells under various experimental conditions to compare their outcome with that of mutant embryos or of embryos submitted to exogenous treatments that interfere with Fgf signaling. The results are analyzed by means of bifurcation diagrams. Finally, the model predicts that heterogeneities in extracellular Fgf4 concentration play a primary role in the spatial arrangement of the Epi/PrE cells in a salt-and-pepper pattern. If, instead of heterogeneities in extracellular Fgf4 concentration, internal fluctuations in the levels of expression of the transcription factors are considered as a source of randomness, simulations predict the occurrence of unrealistic switches between the Epi and the PrE cell fates, as well as the evolution of some cells toward one of these states without passing through the previous ICM state, in contrast to what is observed in vivo. PMID- 26840736 TI - Voltage-Sensitive Fluorescence of Indocyanine Green in the Heart. AB - So far, the optical mapping of cardiac electrical signals using voltage-sensitive fluorescent dyes has only been performed in experimental studies because these dyes are not yet approved for clinical use. It was recently reported that the well-known and widely used fluorescent dye indocyanine green (ICG), which has FDA approval, exhibits voltage sensitivity in various tissues, thus raising hopes that electrical activity could be optically mapped in the clinic. The aim of this study was to explore the possibility of using ICG to monitor cardiac electrical activity. Optical mapping experiments were performed on Langendorff rabbit hearts stained with ICG and perfused with electromechanical uncouplers. The residual contraction force and electrical action potentials were recorded simultaneously. Our research confirms that ICG is a voltage-sensitive dye with a dual-component (fast and slow) response to membrane potential changes. The fast component of the optical signal (OS) can have opposite polarities in different parts of the fluorescence spectrum. In contrast, the polarity of the slow component remains the same throughout the entire spectrum. Separating the OS into these components revealed two different voltage-sensitivity mechanisms for ICG. The fast component of the OS appears to be electrochromic in nature, whereas the slow component may arise from the redistribution of the dye molecules within or around the membrane. Both components quite accurately track the time of electrical signal propagation, but only the fast component is suitable for estimating the shape and duration of action potentials. Because ICG has voltage-sensitive properties in the entire heart, we suggest that it can be used to monitor cardiac electrical behavior in the clinic. PMID- 26840737 TI - Ca2+ Effects on ATP Production and Consumption Have Regulatory Roles on Oscillatory Islet Activity. AB - Pancreatic islets respond to elevated blood glucose by secreting pulses of insulin that parallel oscillations in beta-cell metabolism, intracellular Ca(2+) concentration, and bursting electrical activity. The mechanisms that maintain an oscillatory response are not fully understood, yet several models have been proposed. Only some can account for experiments supporting that metabolism is intrinsically oscillatory in beta-cells. The dual oscillator model (DOM) implicates glycolysis as the source of oscillatory metabolism. In the companion article, we use recently developed biosensors to confirm that glycolysis is oscillatory and further elucidate the coordination of metabolic and electrical signals in the insulin secretory pathway. In this report, we modify the DOM by incorporating an established link between metabolism and intracellular Ca(2+) to reconcile model predictions with experimental observations from the companion article. With modification, we maintain the distinguishing feature of the DOM, oscillatory glycolysis, but introduce the ability of Ca(2+) influx to reshape glycolytic oscillations by promoting glycolytic efflux. We use the modified model to explain measurements from the companion article and from previously published experiments with islets. PMID- 26840739 TI - Advances in ureteral stent development. AB - PURPOSE OF REVIEW: Ureteral stents are commonly used in urology, but there is no perfect ureteral stent. This review documents developing ureteral technologies and strategies over the past 2 years. This area has some progressive advances in the foreseeable future. RECENT FINDINGS: Publications from 2014 and 2015 from a PubMed search with the words 'ureter' and 'stent' in the title were reviewed. Topics that affected patient symptoms from stents include selecting the proper length of stent, patient education regarding stent symptoms, and how the stent is removed. Stent extraction strings have been studied and not increased the incidence of infection or pain. There have been several publications examining antirefluxing ureteral stents that reduced vesicoureteral reflux during micturition and infection of transplanted kidneys. Other novel methods of removing a stent include new biodegradable ureteral stents and metal beads attached to the stent used in tandem with a magnetic catheter. Several new metal and mesh stents were described for use in patients with malignant ureteral obstruction. Last, new stent coatings with antimicrobial peptides have also been described. SUMMARY: The search continues for the perfect stent and there has been promising progress over the past 2 years. PMID- 26840738 TI - Modeling the Overproduction of Ribosomes when Antibacterial Drugs Act on Cells. AB - Bacteria that are subjected to ribosome-inhibiting antibiotic drugs show an interesting behavior: Although the drug slows down cell growth, it also paradoxically increases the cell's concentration of ribosomes. We combine our earlier nonlinear model of the energy-biomass balance in undrugged Escherichia coli cells with Michaelis-Menten binding of drugs that inactivate ribosomes. Predictions are in good agreement with experiments on ribosomal concentrations and synthesis rates versus drug concentrations and growth rates. The model indicates that the added drug drives the cell to overproduce ribosomes, keeping roughly constant the level of ribosomes producing ribosomal proteins, an important quantity for cell growth. The model also predicts that ribosomal production rates should increase and then decrease with added drug. This model gives insights into the driving forces in cells and suggests new experiments. PMID- 26840741 TI - Days Out of Role Due to Mental and Physical Conditions: Results from the Singapore Mental Health Study. AB - OBJECTIVE: The aim of the current study was to evaluate the relative contributions of mental and physical conditions to days out of role among adults aged 18 years and above in Singapore. METHODS: The Singapore Mental Health Study was a cross-sectional epidemiological survey of a nationally representative sample of residents aged 18 years or older. Diagnosis of mental disorders was established using the Composite International Diagnostic Interview; while chronic physical conditions were established using a checklist. Days out of role were assessed using a WHO Disability Assessment Schedule item. Multivariate regression analyses were used to estimate individual-level and societal-level effects of disorders. RESULTS: Overall, 8.7% of respondents reported at least one day out of role, with a mean of 5.8 days. The most disabling conditions at the individual level were cancer (118.9 additional days), cardiovascular diseases (93.5), and bipolar disorder (71.0). At the societal level, cardiovascular diseases contributed the highest population attributable risk proportion (45%), followed by cancer (39.3%), and hypertension (13.5%). CONCLUSIONS: Mental and physical conditions are linked to significant losses in productivity for society as well as role disability for individuals, underscoring the need to enhance prevention and intervention efforts to increase overall productivity and improve individual functioning. PMID- 26840740 TI - Impedance Changes and Fibrous Tissue Growth after Cochlear Implantation Are Correlated and Can Be Reduced Using a Dexamethasone Eluting Electrode. AB - BACKGROUND: The efficiency of cochlear implants (CIs) is affected by postoperative connective tissue growth around the electrode array. This tissue formation is thought to be the cause behind post-operative increases in impedance. Dexamethasone (DEX) eluting CIs may reduce fibrous tissue growth around the electrode array subsequently moderating elevations in impedance of the electrode contacts. METHODS: For this study, DEX was incorporated into the silicone of the CI electrode arrays at 1% and 10% (w/w) concentration. Electrodes prepared by the same process but without dexamethasone served as controls. All electrodes were implanted into guinea pig cochleae though the round window membrane approach. Potential additive or synergistic effects of electrical stimulation (60 minutes) were investigated by measuring impedances before and after stimulation (days 0, 7, 28, 56 and 91). Acoustically evoked auditory brainstem responses were recorded before and after CI insertion as well as on experimental days 7, 28, 56, and 91. Additionally, histology performed on epoxy embedded samples enabled measurement of the area of scala tympani occupied with fibrous tissue. RESULTS: In all experimental groups, the highest levels of fibrous tissue were detected in the basal region of the cochlea in vicinity to the round window niche. Both DEX concentrations, 10% and 1% (w/w), significantly reduced fibrosis around the electrode array of the CI. Following 3 months of implantation impedance levels in both DEX-eluting groups were significantly lower compared to the control group, the 10% group producing a greater effect. The same effects were observed before and after electrical stimulation. CONCLUSION: To our knowledge, this is the first study to demonstrate a correlation between the extent of new tissue growth around the electrode and impedance changes after cochlear implantation. We conclude that DEX-eluting CIs are a means to reduce this tissue reaction and improve the functional benefits of the implant by attenuating electrode impedance. PMID- 26840742 TI - Differentiation of Vascular Stem Cells Contributes to Ectopic Calcification of Atherosclerotic Plaque. AB - The cellular and molecular basis of vascular calcification (VC) in atherosclerosis is not fully understood. Here, we investigate role of resident/circulating progenitor cells in VC and contribution of inflammatory plaque environment to this process. Vessel-derived stem/progenitor cells (VSCs) and mesenchymal stem cells (MSCs) isolated from atherosclerotic ApoE(-/-) mice showed significantly more in vitro osteogenesis and chondrogenesis than cells generated from control C57BL/6 mice. To assess their ability to form bone in vivo, cells were primed chondrogenically or cultured in control medium on collagen glycosaminoglycan scaffolds in vitro prior to subcutaneous implantation in ApoE(-/-) and C57BL/6 mice using a crossover study design. Atherosclerotic ApoE(-/-) MSCs and VSCs formed bone when implanted in C57BL/6 mice. In ApoE(-/-) mice, these cells generated more mature bone than C57BL/6 cells. The atherosclerotic in vivo environment alone promoted bone formation by implanted C57BL/6 cells. Un-primed C57BL/6 VSCs were unable to form bone in either mouse strain. Treatment of ApoE(-/-) VSC chondrogenic cultures with interleukin (IL)-6 resulted in significantly increased glycosaminoglycan deposition and expression of characteristic chondrogenic genes at 21 days. In conclusion, resident vascular cells from atherosclerotic environment respond to the inflammatory milieu and undergo calcification. IL-6 may have a role in aberrant differentiation of VSCs contributing to vascular calcification in atherosclerosis. PMID- 26840744 TI - Spatial and Temporal Examination of Bivalve Communities in Several Estuaries of Southern California and Northern Baja California, MX. AB - A combination of historical bivalve surveys spanning 30-50 years and contemporary sampling were used to document the changes in bivalve community structure over time at four southern California and one northern Baja California estuaries. While there are limitations to the interpretation of historic data, we observed generally similar trends of reduced total bivalve species richness, losses of relatively large and/or deeper-dwelling natives, and gains of relatively small, surface dwelling introduced species across the southern California estuaries, despite fairly distinct bivalve communities. A nearly 50-year absence of bivalves from two wetlands surveyed in a Baja California estuary continued. A combination of site history and current characteristics (e.g., location, depth) likely contributes to maintenance of distinct communities, and both episodic and gradual environmental changes likely contribute to within-estuary temporal shifts (or absences). We highlight future research needed to determine mechanisms underlying patterns so that we can better predict responses of bivalve communities to future scenarios, including climate change and restoration. PMID- 26840743 TI - Urocortin-1 Mediated Cardioprotection Involves XIAP and CD40-Ligand Recovery: Role of EPAC2 and ERK1/2. AB - AIMS: Urocortin-1 (Ucn-1) is an endogenous peptide that protects heart from ischemia and reperfusion (I/R) injuries. Ucn-1 is known to prevent cardiac cell death, but its role in the transcription of specific genes related to survival signaling pathway has not been fully defined. The aim of this study was to investigate the molecular signaling implicated in the improvement of cardiac myocytes survival induced by Ucn-1. METHODS AND RESULTS: Ucn-1 administration before ischemia and at the onset of reperfusion, in rat hearts perfused in Langendorff system, fully recovered heart contractility and other hemodynamic parameters. Ucn-1 enhanced cell viability and decreased lactate dehydrogenase (LDH) release in adult cardiac myocytes subjected to simulated I/R. Annexin V FITC/PI staining indicated that Ucn-1 promoted cell survival and decreased cell necrosis through Epac2 (exchange protein directly activated by cAMP) and ERK1/2 (extracellular signal-regulated kinases 1/2) activation. We determined that Ucn-1 shifted cell death from necrosis to apoptosis and activated caspases 9 and 3/7. Furthermore, mini-array, RT-qPCR and protein analyses of apoptotic genes showed that Ucn-1 upregulated the expression of CD40lg, Xiap and BAD in cells undergoing I/R, involving Epac2 and ERK1/2 activation. CONCLUSIONS: Our data indicate that Ucn-1 efficiently protected hearts from I/R damage by increasing the cell survival and stimulated apoptotic genes, CD40lg, Xiap and BAD, overexpression through the activation of Epac2 and ERK1/2. PMID- 26840745 TI - Measuring pregnancy care: towards better maternal and child health. AB - BACKGROUND: Obstetrics remains the largest medico-legal liability in healthcare. Neither an increasing awareness of patient safety nor a long tradition of reporting obstetric outcomes have reduced either rates of medical error or obstetric litigation. International debate continues about the best approaches to measuring and improving patient safety. In this study, we set out to assess the feasibility and utility of measuring the process of maternity care provision rather than care outcomes. AIMS: To report the development, application and results of a tool designed to measure the process of maternity care. MATERIALS AND METHODS: A dedicated audit tool was developed, informed by local, national and international standards guiding best practice and then applied to a convenience sample of individual healthcare records as proof of function. Omissions of care were rated in order of severity (low, medium or high) based on the likelihood of serious consequences on patient safety and outcome. RESULTS: The rate of high severity omissions of care was less that 2%. However, overall rates of all omissions varied from 0 to 99%, highlighting key areas for clinical practice improvement. CONCLUSIONS: Measuring process of care provision, rather than pregnancy outcomes, is feasible and insightful, effectively identifying gaps in care provision and affording opportunities for targeted care improvement. This approach to improving patient safety, and potentially reducing litigation burden, promises to be a useful adjunct to the measurement of outcomes. PMID- 26840747 TI - Metal-Free Radical Oxidative Annulation of Ynones with Alkanes To Access Indenones. AB - The benzoyl peroxide (BPO) promoted carboannulation of ynones with alkanes is developed, affording a series of 2-alkyl-3-aryl indenones in moderate to good yields. The procedure involves direct functionalization of alkane C(sp(3))-H and arene C(sp(2))-H bonds under metal-free conditions, providing a favorable approach for indenone synthesis. PMID- 26840748 TI - Naphthalene cytotoxicity in microsomal epoxide hydrolase deficient mice. AB - Naphthalene (NA) is a ubiquitous pollutant to which humans are widely exposed. 1,2-Dihydro-1,2-dihydroxynaphthalene (NA-dihydrodiol) is a major metabolite of NA generated by microsomal epoxide hydrolase (mEH). To investigate the role of the NA-dihydrodiol and subsequent metabolites (i.e. 1,2-naphthoquinone) in cytotoxicity, we exposed both male and female wild type (WT) and mEH null mice (KO) to NA by inhalation (5, 10, 20 ppm for 4h). NA-dihydrodiol was ablated in the KO mice. High-resolution histopathology was used to study site-specific cytotoxicity, and formation of naphthalene metabolites was measured by HPLC in microdissected airways. Swollen and vacuolated airway epithelial cells were observed in the intra- and extrapulmonary airways of all mice at and below the current OSHA standard (10 ppm). Female mice may be more susceptible to this acute cytotoxicity. In the extrapulmonary airways, WT mice were more susceptible to damage than KO mice, indicating that the metabolites associated with mEH-mediated metabolism could be partially responsible for cytotoxicity at this site. The level of cytotoxicity in the mEH KO mice at all airway levels suggests that non mEH metabolites are contributing to NA cellular damage in the lung. Our results indicate that the apparent contribution of mEH-dependent metabolites to toxicity differs by location in the lung. These studies suggest that metabolites generated through the mEH pathway may be of minor importance in distal airway toxicity and subsequent carcinogenesis from NA exposure. PMID- 26840749 TI - Sc2O@C(3v)(8)-C82: A Missing Isomer of Sc2O@C82. AB - By introducing CO2 as the oxygen source during the arcing process, a new isomer of Sc2O@C82, Sc2O@C(3v)(8)-C82, previously investigated only by computational studies, was discovered and characterized by mass spectrometry, UV-vis-NIR absorption spectroscopy, cyclic voltammetry, (45)Sc NMR, density functional theory (DFT) calculations, and single-crystal X-ray diffraction. The crystallographic analysis unambiguously elucidated that the cage symmetry was assigned to C(3v)(8) and suggests that Sc2O cluster is disordered inside the cage. The comparative studies of crystallographic data further reveal that the Sc1-O-Sc2 angle is in the range of 131.0-148.9 degrees , much larger than that of the Sc2S@C(3v)(8)-C82, demonstrating a significant flexibility of dimetallic clusters inside the cages. The electrochemical studies show that the electrochemical gap of Sc2O@C(3v)(8)-C82 is 1.71 eV, the largest among those of the oxide cluster fullerenes (OCFs) reported so far, well correlated with its rich abundance in the reaction mixture of OCF synthesis. Moreover, the comparative electrochemical studies suggest that both the dimetallic clusters and the cage structures have major influences on the electronic structures of the cluster fullerenes. Computational studies show that the cluster can rotate and change the Sc-O-Sc angle easily at rather low temperature. PMID- 26840750 TI - A Loss Unlike Any Other. PMID- 26840746 TI - De Novo Assembled Wheat Transcriptomes Delineate Differentially Expressed Host Genes in Response to Leaf Rust Infection. AB - Pathogens like Puccinia triticina, the causal organism for leaf rust, extensively damages wheat production. The interaction at molecular level between wheat and the pathogen is complex and less explored. The pathogen induced response was characterized using mock- or pathogen inoculated near-isogenic wheat lines (with or without seedling leaf rust resistance gene Lr28). Four Serial Analysis of Gene Expression libraries were prepared from mock- and pathogen inoculated plants and were subjected to Sequencing by Oligonucleotide Ligation and Detection, which generated a total of 165,767,777 reads, each 35 bases long. The reads were processed and multiple k-mers were attempted for de novo transcript assembly; 22 k-mers showed the best results. Altogether 21,345 contigs were generated and functionally characterized by gene ontology annotation, mining for transcription factors and resistance genes. Expression analysis among the four libraries showed extensive alterations in the transcriptome in response to pathogen infection, reflecting reorganizations in major biological processes and metabolic pathways. Role of auxin in determining pathogenesis in susceptible and resistant lines were imperative. The qPCR expression study of four LRR-RLK (Leucine-rich repeat receptor-like protein kinases) genes showed higher expression at 24 hrs after inoculation with pathogen. In summary, the conceptual model of induced resistance in wheat contributes insights on defense responses and imparts knowledge of Puccinia triticina-induced defense transcripts in wheat plants. PMID- 26840752 TI - Chronic Hepatitis B Virus Infection: Disease Revisit and Management Recommendations. AB - Chronic hepatitis B virus (HBV) infection evolves from immune-tolerance phase, through immune clearance phase to a quiescent phase or reactivation as hepatitis B e antigen-negative hepatitis. Persistent infection may result in the development of cirrhosis and hepatocellular carcinoma (HCC). Host factors including gender, age, family history, HLA-DP, and viral factors including HBV DNA, genotypes, precore mutations, pre-S deletions, and hepatitis B surface antigen (HBsAg) level are associated with the development of these complications. Risk scores for the development of HCC have been derived. Patients with persistently elevated alanine aminotransferase levels (>30 for males; >19 U/L for females) and HBV DNA levels >2000 IU/mL should be treated. Patients with established cirrhosis with detectable HBV DNA should also be treated. The recommended first-line agents include pegylated interferon and 2 nucleos(t)ide analogs, entecavir and tenofovir. NAs require long-term treatment to maintain suppression of HBV DNA. They have been shown to decrease hepatic fibrosis, or reverse cirrhosis and to reduce the development of HCC. They have very low rates (0% to 1.2%) of resistance. HBsAg seroclearance, although the ideal endpoint, is only achievable in 10% to 12% of patients by multicenter trials usually studying relatively young patients. Patients on long-term treatment should be monitored for viral breakthrough that may be due to noncompliance or the development of resistance. Newer agents are under trials to enhance the rate of HBsAg seroclearance. However, even with the current NAs, long-term treatment of >6 years can markedly reduce the covalently closed circular DNA, the viral component responsible for initiation of viral replication. PMID- 26840753 TI - Direct Regioselective gamma-Amination of Enones. AB - Carbonyl compounds bearing a gamma-amino group are valuable pharmacologically active targets. Regioselective gamma-C-N bond formation is achieved with simple enone substrates through controlled dienolate reactivity toward azodicarboxylate electrophiles. The amination reaction occurs readily with sterically demanding nucleophiles and is stereoselective. PMID- 26840751 TI - Tissue-Integratable and Biocompatible Photogelation by the Imine Crosslinking Reaction. AB - A novel photogelling mechanism by the phototriggered-imine-crosslinking (PIC) reaction is demonstrated. Hyaluronic acid grafted with o-nitrobenzene, a photogenerated aldehyde group, can quickly photo-crosslink with amino-bearing polymers or proteins. Once the in situ photogelling on a wound occurs, the PIC gelling process can well integrate a hydrogel with surrounding tissue by covalent bonding, thus making it a powerful tool for tissue engineering and regenerative medicine. PMID- 26840754 TI - Interprofessional learning on polypharmacy. AB - BACKGROUND: Prescribing errors remain a continuing patient safety concern. Eradicating error in prescribing requires closer working between doctors and pharmacists. We report on interprofessional learning for medical and pharmacy students on complex polypharmacy in older people. This short course enables final year students to work with in-patients to meticulously assess the completeness and accuracy of their prescriptions. The learning theory applied is experiential learning and reflection. METHODS: A mixed-method evaluation study was used to examine students' learning, using a questionnaire, case presentations and ward feedback forms. The quantitative questionnaire data were analysed using spss and qualitative data were analysed using thematic analysis; case presentations and feedback forms were analysed using content analysis. RESULTS: A total of 525 students (294 medical students and 231 pharmacy students) participated in the course. The students' self-ratings suggested significant advances in their knowledge (p < 0.001). The main emerging themes related to the value of collaborative learning, new insights into the management of polypharmacy in older people and how to achieve effective communication to ensure medication safety. In depth analysis of 58 in-patient cases identified drug errors concerning STOPP/START guidelines, unclear prescriptions and drug interactions. Eradicating error in prescribing requires closer working between doctors and pharmacists DISCUSSION: Medical and pharmacy students seemed to value collaborative practise to jointly analyse the complexity of polypharmacy in older people. This evaluation highlights the potential benefits of real-life experiential training followed by reflection and analyses to propel student learning and to help practice teams. PMID- 26840756 TI - Equation of state for water and its line of density maxima down to -120 MPa. AB - As water is involved in countless natural and industrial processes, its thermodynamic properties have been measured in a wide temperature and pressure range. Data on supercooled water are also available down to -73 degrees C and up to 400 MPa. In contrast, data at negative pressures are extremely scarce. Here we provide an experimental equation of state for water down to -120 MPa. In particular, we obtain the line of density maxima (LDM) of water down to a pressure six times more negative than previously available. As temperature increases from 4 up to 18 degrees C, the pressure PLDM(T) along the LDM decreases monotonically from 0 down to -120 MPa, while the slope dPLDM/dT becomes more negative. The experimental results are compared with molecular dynamic simulations of TIP4P/2005 water and a two-state model. We also discuss the possibility to observe extrema in compressibility and heat capacity at negative pressures, features that have remained elusive at positive pressures. PMID- 26840755 TI - Novel PTCH1 Mutation in a Young Child With Gorlin Syndrome and Medulloblastoma. PMID- 26840757 TI - High Conductive Two-Dimensional Covalent Organic Framework for Lithium Storage with Large Capacity. AB - A high conductive 2D COF polyporphyrin (TThPP) linked by 4-thiophenephenyl groups was synthesized through an in situ chemical oxidative polymerization on the surface of copper foil. The TThPP films were used as the anode of lithium-ion battery, which exhibited high specific capacities, excellent rate performances, and long cycle lives due to the alignment of 2D polyporphyrin nanosheets, and they (i) can highly efficiently adsorb Li atoms, (ii) have short-ended paths for the fast lithium ion diffusion, and (iii) open nanopores holding electrolyte. The reversible capacity is up to 666 mAh/g. This is the first example of an organic 2D COF for an anode of lithium-ion battery and represents an important step toward the use of COFs in the next-generation high-performance lithium-ion battery. PMID- 26840758 TI - Socioeconomic disparities in childhood cancer survival in Switzerland. AB - In this study, we investigated whether childhood cancer survival in Switzerland is influenced by socioeconomic status (SES), and if disparities vary by type of cancer and definition of SES (parental education, living condition, area-based SES). Using Cox proportional hazards models, we analyzed 5-year cumulative mortality in all patients registered in the Swiss Childhood Cancer Registry diagnosed 1991-2006 below 16 years. Information on SES was extracted from the Swiss census by probabilistic record linkage. The study included 1602 children (33% with leukemia, 20% with lymphoma, 22% with central nervous system (CNS) tumors); with an overall 5-year survival of 77% (95%CI 75-79%). Higher SES, particularly parents' education, was associated with a lower 5-year cumulative mortality. Results varied by type of cancer with no association for leukemia and particularly strong effects for CNS tumor patients, where mortality hazard ratios for the different SES indicators, comparing the highest with the lowest group, ranged from 0.48 (95%CI: 0.28-0.81) to 0.71 (95%CI: 0.44-1.15). We conclude that even in Switzerland with a high quality health care system and mandatory health insurance, socioeconomic differences in childhood cancer survival persist. Factors causing these survival differences have to be further explored, to facilitate universal access to optimal treatment and finally eliminate social inequalities in childhood cancer survival. PMID- 26840759 TI - A facile route to core-shell nanoparticulate formation of arsenic trioxide for effective solid tumor treatment. AB - Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a "one-pot" method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core shell embedding method endows nanodrugs with high loading capacity (57.9 wt%) and a prolonged pH-responsive releasing profile, which is crucial to increase the drug concentration at tumor sites and improve the drug efficacy. Based on these unique features, the nanodrugs significantly inhibit the growth of solid tumors without adverse side effects. Therefore, we anticipate that the arsenic-based nanodrugs generated by this facile synthetic route may be a powerful and alternative strategy for solid tumor therapy. PMID- 26840760 TI - Direct immersion solid-phase microextraction with gas chromatography and mass spectrometry for the determination of specific biomarkers of human sweat in melted snow. AB - To provide a reliable tool for investigating diffusion processes of the specific components of the human odor 3-hydroxy-3-methylhexanoic acid and 3-methyl-3 sulfanylhexan-1-ol through the snowpack, we developed and optimized an analytical method based on direct immersion solid-phase microextraction followed by gas chromatography with mass spectrometry. Direct immersion solid-phase microextraction was performed using polyacrylate fibers placed in aqueous solutions containing 3-hydroxy-3-methylhexanoic acid and 3-methyl-3-sulfanylhexan 1-ol. After optimization, absorption times of 120 min provided a good balance to shorten the analysis time and to obtain suitable amounts of extractable analytes. The extraction efficiency was improved by increasing the ionic strength of the solution. Although the absolute extraction efficiency ranged between 10 and 12% for 3-hydroxy-3-methylhexanoic acid and 2-3% for 3-methyl-3-sulfanylhexan-1-ol, this method was suitable for analyzing 3-hydroxy-3-methylhexanoic acid and 3 methyl-3-sulfanylhexan-1-ol concentrations of at least 0.04 and 0.20 ng/mL, respectively. The precision of the direct immersion solid-phase microextraction method ranged between 8 and 16%. The variability within a batch of six fibers was 10-18%. The accuracy of the method provided values of 88-95 and 86-101% for 3 hydroxy-3-methylhexanoic acid and 3-methyl-3-sulfanylhexan-1-ol, respectively. The limit of detection (and quantification) was 0.01 ng/mL (0.04 ng/mL) for 3 hydroxy-3-methylhexanoic acid and 0.06 ng/mL (0.20 ng/mL) for 3-methyl-3 sulfanylhexan-1-ol. The signal versus concentration was linear for both compounds (r(2) = 0.973-0.979). The stability of these two compounds showed that 3-hydroxy 3-methylhexanoic acid was more stable in water than 3-methyl-3-sulfanylhexan-1 ol. We applied the method to environmental samples in correspondence with an olfactory target buried previously. PMID- 26840761 TI - Gene expression signatures associated with suppression of TRAMP prostate carcinogenesis by a kavalactone-rich Kava fraction. AB - Kava (Piper methysticum Forster) extract and its major kavalactones have been shown to block chemically induced lung tumor initiation in mouse models. Here we evaluated the chemopreventive effect of a kavalactone-rich Kava fraction B (KFB), free of flavokavains, on carcinogenesis in a transgenic adenocarcinoma of mouse prostate (TRAMP) model and characterized the prostate gene expression signatures. Male C57BL/6 TRAMP mice were fed AIN93M diet with or without 0.4% KFB from 8 wk of age. Mice were euthanized at 16 or 28 wk. The growth of the dorsolateral prostate (DLP) lobes in KFB-treated TRAMP mice was inhibited by 66% and 58% at the respective endpoint. Anterior and ventral prostate lobes in KFB-treated TRAMP mice were suppressed by 40% and 49% at 28 wk, respectively. KFB consumption decreased cell proliferation biomarker Ki-67 and epithelial lesion severity in TRAMP DLP, without detectable apoptosis enhancement. Real time qRT-PCR detection of mRNA from DLP at 28 wk showed decreased expression of cell cycle regulatory genes congruent with Ki-67 suppression. Microarray profiling of DLP mRNA indicated that "oncogene-like" genes related to angiogenesis and cell proliferation were suppressed by KFB but tumor suppressor, immunity, muscle/neuro, and metabolism-related genes were upregulated by KFB in both TRAMP and WT DLP. TRAMP mice fed KFB diet developed lower incidence of neuroendocrine carcinomas (NECa) (2 out of 14 mice) than those fed the basal diet (8 out of 14 mice, chi2 = 5.6, P < 0.025). KFB may, therefore, inhibit not only TRAMP DLP epithelial lesions involving multiple molecular pathways, but also NECa. (c) 2016 Wiley Periodicals, Inc. PMID- 26840763 TI - Presentation, clinical pathological and post-mortem findings in three related Scottish terriers with ligneous membranitis. AB - Ligneous conjunctivitis and gingivitis were diagnosed in three related Scottish terrier dogs presented for investigation of severe conjunctivitis and respiratory signs. Hypoplasminogenaemia was confirmed in one of the three affected dogs. Supportive treatment was not effective, and the dogs died or were euthanased because of the disease. Post-mortem analysis of two of the dogs revealed multiple abnormalities including severe proliferative fibrinous lesions affecting the conjunctiva, gingiva, trachea, larynx and epicardium and multiple fibrous adhesions throughout the thoracic and abdominal cavities. One dog had internal hydrocephalus and lacked a cerebellar vermis. Ligneous membranitis was confirmed on histopathology. This is a rare condition in dogs but an important differential diagnosis for severe conjunctivitis and gingivitis. PMID- 26840762 TI - Eosinophilic gastroenteritis in a patient with Bruton's tyrosine kinase deficiency. AB - Eosinophilic gastrointestinal diseases (EGID) are relatively rare diseases characterized by eosinophilic infiltration of the gastrointestinal tract resulting in various gastrointestinal symptoms. EGID are often caused by allergic reactions or systemic eosinophilic disorders, but their comorbidity with Bruton's tyrosine kinase (BTK) deficiency has not been previously documented. Here, we report a case of eosinophilic gastroenteritis (EG) in a patient with BTK deficiency. Despite adequate replacement immunoglobulin (Ig) therapy, trough serum IgG was not maintained. To identify the underlying cause of the low trough level and chronic diarrhea, the intestine was investigated on endoscopy. We also screened for the variable number of tandem repeat polymorphism in FCGRT. Genetic analysis could not explain the low trough IgG, but endoscopy indicated eosinophilic enterocolitis. EG may be an important differential diagnosis when primary immunodeficiency patients have chronic diarrhea or continued low serum IgG. PMID- 26840764 TI - Atomic force microscopy study of ionomycin-induced degranulation in RBL-2H3 cells. AB - Mast cell degranulation is the typical anaphylaxis process of mast cells associated with the release of cytokines, eicosanoids and their secretory granules, which play very important roles in the allergic inflammatory response of the human body upon anaphylactogen stimulation. The calcium ionophore ionomycin is widely used as a degranulation induction agent for mast cell degranulation studies. In the present work, ionomycin-induced degranulation of RBL-2H3 basophilic leukemia cell line cells was investigated in vitro by high resolution atomic force microscopy (AFM). Ionomycin, which could increase the intracellular free Ca2+ level and beta-Hexosaminidase release, was found to induce the formation of a kind of peculiar vesicles in the cytoplasm area of RBL 2H3 cells. Those vesicles induced by ionomycin would desintegrate to release a larger amount of granules surrounding RBL-2H3 cells by the controlling of F actin. These results provide the precise morphological information of ionomycin induced mast cell degranulation at nanoscale, which could benefit our understanding of ionomycin-induced mast cell anaphylaxis model and also validate the applicability of AFM for the detection of allergic inflammatory response in mast cells. SCANNING 38:525-534, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26840765 TI - Gray platelets - artifact or real? PMID- 26840766 TI - 3,4-Phenylenedioxythiophene (PheDOT) Based Hole-Transporting Materials for Perovskite Solar Cells. AB - Two new electron-rich molecules based on 3,4-phenylenedioxythiophene (PheDOT) were synthesized and successfully adopted as hole-transporting materials (HTMs) in perovskite solar cells (PSCs). X-ray diffraction, absorption spectra, photoluminescence spectra, electrochemical properties, thermal stabilities, hole mobilities, conductivities, and photovoltaic parameters of PSCs based on these two HTMs were compared with each other. By introducing methoxy substituents into the main skeleton, the energy levels of PheDOT-core HTM were tuned to match with the perovskite, and its hole mobility was also improved (1.33*10(-4) cm(2) V( 1) s(-1) , being higher than that of spiro-OMeTAD, 2.34*10(-5) cm(2) V(-1) s( 1)). The PSC based on MeO-PheDOT as HTM exhibits a short-circuit current density (Jsc) of 18.31 mA cm(-2) , an open-circuit potential (Voc ) of 0.914 V, and a fill factor (FF) of 0.636, yielding an encouraging power conversion efficiency (PCE) of 10.64 % under AM 1.5G illumination. These results give some insight into how the molecular structures of HTMs affect their performances and pave the way for developing high-efficiency and low-cost HTMs for PSCs. PMID- 26840768 TI - Response to Re: Contact lens management of keratoconus. PMID- 26840767 TI - Hepatitis E virus as a Cause of Acute Hepatitis in The Netherlands. AB - BACKGROUND: Recent studies indicate that 27% of Dutch blood donors have evidence of past infection with HEV. However, the low number of diagnosed HEV infections indicates either an asymptomatic course or under diagnosis. OBJECTIVES: We investigated whether HEV is a cause of acute hepatitis in Dutch patients and which diagnostic modality (serology or PCR) should be used for optimal detection. STUDY DESIGN: Serum samples were retrospectively selected from non-severely immuno-compromised patients from a university hospital population, suspected of having an infectious hepatitis. Criteria were: elevated alanine aminotransferase (ALT> 34 U/l) and request for antibody testing for CMV, EBV or Hepatitis A (HAV). RESULTS: All samples were tested for HEV using ELISA and PCR. Ninety patients/sera were tested, of which 22% were HEV IgG positive. Only one serum was IgM positive. HEV PCR was positive in two patients: one patient was both HEV IgM and IgG positive, the other patient was only IgG positive. Both HEV RNA positive samples belonged to genotype 3. Evidence of recent infection with CMV, EBV and HAV was found in 13%, 10% and 3% respectively. CONCLUSIONS: Although our study is limited by small numbers, we conclude that HEV is a cause of acute hepatitis in hospital associated patients in The Netherlands. Moreover, in our study population the prevalence of acute HAV (3%) was almost similar to acute HEV (2%). We propose to incorporate HEV testing in panels for acute infectious hepatitis. Negative results obtained for HEV IgM in a HEV PCR positive patient, indicates that antibody testing alone may not be sufficient and argues for PCR as a primary diagnostic tool in hospital associated patients. The high percentage of HEV IgG seropositivity confirms earlier epidemiological studies. PMID- 26840770 TI - A scoping review of female disadvantage in health care use among very young children of immigrant families. AB - Preference for sons culminates in higher mortality and inadequate immunizations and health care visits for girls compared to boys in several countries. It is unknown if the negative consequences of son-preference persist among those who immigrate to Western, high-income countries. To review the literature regarding gender inequities in health care use among children of parents who migrate to Western, high-income countries, we completed a scoping literature review using Medline, Embase, PsycINFO and Scopus databases. We identified studies reporting gender-specific health care use by children aged 5 years and younger whose parents had migrated to a Western country. Two independent reviewers conducted data extraction and a quality assessment tool was applied to each included study. We retrieved 1547 titles, of which 103 were reviewed in detail and 12 met our inclusion criteria. Studies originated from the United States and Europe, using cross-sectional or registry-based designs. Five studies examined gender differences in health care use within immigrant groups, and only one study explored the female health disadvantage hypothesis. No consistent gender differences were observed for routine primary care visits however immunizations and prescriptions were elevated for boys. Greater use of acute health services, namely emergency department visits and hospitalizations, was observed for boys over girls in several studies. Studies did not formally complete gender-based analyses or assess for acculturation factors. Health care use among children in immigrant families may differ between boys and girls, but the reasons for why this is so are largely unexplored. Further gender-based research with attention paid to the diversity of immigrant populations may help health care providers identify children with unmet health care needs. PMID- 26840769 TI - Computational Analysis of AMPK-Mediated Neuroprotection Suggests Acute Excitotoxic Bioenergetics and Glucose Dynamics Are Regulated by a Minimal Set of Critical Reactions. AB - Loss of ionic homeostasis during excitotoxic stress depletes ATP levels and activates the AMP-activated protein kinase (AMPK), re-establishing energy production by increased expression of glucose transporters on the plasma membrane. Here, we develop a computational model to test whether this AMPK mediated glucose import can rapidly restore ATP levels following a transient excitotoxic insult. We demonstrate that a highly compact model, comprising a minimal set of critical reactions, can closely resemble the rapid dynamics and cell-to-cell heterogeneity of ATP levels and AMPK activity, as confirmed by single-cell fluorescence microscopy in rat primary cerebellar neurons exposed to glutamate excitotoxicity. The model further correctly predicted an excitotoxicity induced elevation of intracellular glucose, and well resembled the delayed recovery and cell-to-cell heterogeneity of experimentally measured glucose dynamics. The model also predicted necrotic bioenergetic collapse and altered calcium dynamics following more severe excitotoxic insults. In conclusion, our data suggest that a minimal set of critical reactions may determine the acute bioenergetic response to transient excitotoxicity and that an AMPK-mediated increase in intracellular glucose may be sufficient to rapidly recover ATP levels following an excitotoxic insult. PMID- 26840771 TI - The effect of peers on HIV infection expectations among Malawian adolescents: Using an instrumental variables/school fixed effect approach. AB - Malawian adolescents overestimate their HIV infection risk. Understanding why they do so is important since such overestimation is likely to be linked to later life outcomes. This study focuses on the influence peers have on HIV infection expectations. I use novel school-based survey data collected in Malawi between October 2011 and March 2012 (n = 7910), which has more reliable measures of peers' HIV infection expectations than other studies. I employ a combined instrumental variables/fixed effects methodology designed to addresses several methodological challenges in estimating peer effects, including self-selection of friends, the issue of unobserved environmental confounders, and the bi directionality of peer effects. Several tests are conducted in order to assess the robustness of the specifications. Results suggest that a one-percentage-point increase in the mean probabilistic expectation of HIV infection among peers increases an adolescent's own subjective expectation of infection by an average of 0.65 percentage points. This paper shows that peer influence is greater for males than for females. Results also suggest that the peer effects on HIV infection expectations are only statistically significant among those lacking more complete knowledge of HIV/AIDS. PMID- 26840772 TI - Biphasic effect of Syzygium aromaticum flower bud on reproductive physiology of male mice. AB - The flower buds of Syzygium aromaticum (clove) have been used for the treatment of male sexual disorders in indigenous medicines of Indian subcontinent. Therefore to evaluate the efficacy of Syzygium aromaticum on the male reproductive health, chronic oral exposure of aqueous extract of flower buds of Syzygium in three doses (15 mg, 30 mg and 60 mg kg-1 BW) were studied for a single spermatogenic cycle (35 days) in Parkes (P) strain mice. Lower dose (15 mg) of Syzygium aromaticum flower buds increased serum testosterone level and testicular hydroxysteroid dehydrogenase (HSD) activities and improved sperm motility, sperm morphology, secretory activity of epididymis and seminal vesicle, and number of litters per female. On the other hand, higher doses (30 and 60 mg) of the treatment adversely affected above parameters. Further, higher doses of the extract also had adverse effects on daily sperm production, 1C cell population and on histology of testis. In conclusion, Syzygium aromaticum flower buds extract exhibits biphasic effect on reproductive physiology of male mice. Lower dose of Syzygium aromaticum flower bud extract is androgenic in nature and may have a viable future as an indigenous sexual rejuvenator, while higher doses adversely affected functional physiology of reproductive organs. PMID- 26840773 TI - A Structure-Guided Switch in the Regioselectivity of a Tryptophan Halogenase. AB - Flavin-dependent halogenases are potentially useful biocatalysts for the regioselective halogenation of aromatic compounds. Haloaromatic compounds can be utilised in the synthesis and biosynthesis of pharmaceuticals and other valuable products. Here we report the first X-ray crystal structure of a tryptophan 6 halogenase (SttH), which enabled key residues that contribute to the regioselectivity in tryptophan halogenases to be identified. Structure-guided mutagenesis resulted in a triple mutant (L460F/P461E/P462T) that exhibited a complete switch in regioselectivity; with the substrate 3-indolepropionate 75 % 5 chlorination was observed with the mutant in comparison to 90 % 6-chlorination for the wild-type SttH. This is the first clear example of how regiocomplementary halogenases can be created from a single parent enzyme. The biocatalytic repertoire of SttH was also expanded to include a range of indolic and non indolic substrates. PMID- 26840774 TI - Novel T-cell epitopes on Schistosoma japonicum SjP40 protein and their preventive effect on allergic asthma in mice. AB - Allergic asthma is a chronic inflammatory disease mediated by Th2 cell immune responses. Currently, immunotherapies based on immune deviation are attractive, preventive, and therapeutic strategies for asthma. Many studies have shown that intracellular bacterial infections such as mycobacteria and their components can suppress asthmatic reactions by enhancing Th1 responses, while helminth infections and their proteins can inhibit allergic asthma via immune regulation. However, some helminth proteins such as SmP40, the major egg antigen of Schistosoma mansoni, are found as Th1 type antigens. Using a panel of overlapping peptides, we identified T-cell epitopes on SjP40 protein of Schistosoma japonicum, which can induce Th1 cytokine and inhibit the production of Th2 cytokines and airway inflammation in a mouse model of allergic asthma. These results reveal a novel form of immune protective mechanism, which may play an important role in the modulating effect of helminth infection on allergic asthmatic reactions. PMID- 26840776 TI - Partitioning of mobile ions between ion exchange polymers and aqueous salt solutions: importance of counter-ion condensation. AB - Equilibrium partitioning of ions between a membrane and a contiguous external solution strongly influences transport properties of polymeric membranes used for water purification and energy generation applications. This study presents a theoretical framework to quantitatively predict ion sorption from aqueous electrolytes (e.g., NaCl, MgCl2) into charged (i.e., ion exchange) polymers. The model was compared with experimental NaCl, MgCl2, and CaCl2 sorption data in commercial cation and anion exchange membranes. Ion sorption in charged polymers was modeled using a thermodynamic approach based on Donnan theory coupled with Manning's counter-ion condensation theory to describe non-ideal behavior of ions in the membrane. Ion activity coefficients in solution were calculated using the Pitzer model. The resulting model, with no adjustable parameters, provides remarkably good agreement with experimental values of membrane mobile salt concentration. The generality of the model was further demonstrated using literature data for ion sorption of various electrolytes in charged polymers, including HCl sorption in Nafion. PMID- 26840775 TI - Field Measurements Indicate Unexpected, Serious Underestimation of Mussel Heart Rates and Thermal Tolerance by Laboratory Studies. AB - Attempts to predict the response of species to long-term environmental change are generally based on extrapolations from laboratory experiments that inevitably simplify the complex interacting effects that occur in the field. We recorded heart rates of two genetic lineages of the brown mussel Perna perna over a full tidal cycle in-situ at two different sites in order to evaluate the cardiac responses of the two genetic lineages present on the South African coast to temperature and the immersion/emersion cycle. "Robomussel" temperature loggers were used to monitor thermal conditions at the two sites over one year. Comparison with live animals showed that robomussels provided a good estimate of mussel body temperatures. A significant difference in estimated body temperatures was observed between the sites and the results showed that, under natural conditions, temperatures regularly approach or exceed the thermal limits of P. perna identified in the laboratory. The two P. perna lineages showed similar tidal and diel patterns of heart rate, with higher cardiac activity during daytime immersion and minimal values during daytime emersion. Comparison of the heart rates measured in the field with data previously measured in the laboratory indicates that laboratory results seriously underestimate heart rate activity, by as much as 75%, especially during immersion. Unexpectedly, field estimates of body temperatures indicated an ability to tolerate temperatures considered lethal on the basis of laboratory measurements. This suggests that the interaction of abiotic conditions in the field does not necessarily raise vulnerability to high temperatures. PMID- 26840777 TI - The Dermal Apron Technique for Immediate Implant Socket Management: A Novel Technique. AB - With immediate implant placement and provisionalization (IIP) in the esthetic zone, measures to counter hard and soft tissue loss are frequently necessary. To reduce the morbidity associated with bone and connective tissue procurement, various exogenous materials are utilized. The "Dermal Apron Technique" presented in this article demonstrates the use of a composite bone particulate (allograft/xenograft) plus a dermal allograft, adapted around screw-retained temporary crowns and secured within a subperiosteal pouch. The purpose is to augment the thickness of peri-implant mucosa for the purpose of preserving ridge dimensions and preventing mucosal recession. Controlled studies are required to further support its use. Clinical significance: Soft tissue health and harmony are critical for successful implant therapy in the esthetic regions of the dentition. Often, autogenous soft tissue grafts are used to augment peri-implant soft tissues. The Dermal Apron Technique is a method, that in specific situations, obviates the need for autogenous grafting. This reduces treatment time and morbidity associated with procurement of these grafts. The Dermal Apron Technique is used simultaneous with immediate placement and provisionalization and can improve long-term esthetic outcomes for patients. PMID- 26840778 TI - Correction: A Role for Na+,K+-ATPase alpha1 in Regulating Rab27a Localisation on Melanosomes. PMID- 26840779 TI - The Effects of Lung Protective Ventilation or Hypercapnic Acidosis on Gas Exchange and Lung Injury in Surfactant Deficient Rabbits. AB - BACKGROUND: Permissive hypercapnia has been shown to reduce lung injury in subjects with surfactant deficiency. Experimental studies suggest that hypercapnic acidosis by itself rather than decreased tidal volume may be a key protective factor. OBJECTIVES: To study the differential effects of a lung protective ventilatory strategy or hypercapnic acidosis on gas exchange, hemodynamics and lung injury in an animal model of surfactant deficiency. METHODS: 30 anesthetized, surfactant-depleted rabbits were mechanically ventilated (FiO2 = 0.8, PEEP = 7cmH2O) and randomized into three groups: Normoventilation-Normocapnia (NN)-group: tidal volume (Vt) = 7.5 ml/kg, target PaCO2 = 40 mmHg; Normoventilation-Hypercapnia (NH)-group: Vt = 7.5 ml/kg, target PaCO2 = 80 mmHg by increasing FiCO2; and a Hypoventilation-Hypercapnia (HH) group: Vt = 4.5 ml/kg, target PaCO2 = 80 mmHg. Plasma lactate and interleukin (IL)-8 were measured every 2 h. Animals were sacrificed after 6 h to perform bronchoalveolar lavage (BAL), to measure lung wet-to-dry weight, lung tissue IL 8, and to obtain lung histology. RESULTS: PaO2 was significantly higher in the HH group compared to the NN-group (p<0.05), with values of the NH-group between the HH- and NN-groups. Other markers of lung injury (wet-dry-weight, BAL-Protein, histology-score, plasma-IL-8 and lung tissue IL-8) resulted in significantly lower values for the HH-group compared to the NN-group and trends for the NH group towards lower values compared to the NN-group. Lactate was significantly lower in both hypercapnia groups compared to the NN-group. CONCLUSION: Whereas hypercapnic acidosis may have some beneficial effects, a significant effect on lung injury and systemic inflammatory response is dependent upon a lower tidal volume rather than resultant arterial CO2 tensions and pH alone. PMID- 26840780 TI - Term elective induction of labour and perinatal outcomes in obese women: retrospective cohort study. AB - OBJECTIVE: To compare perinatal outcomes between elective induction of labour (eIOL) and expectant management in obese women. DESIGN: Retrospective cohort study. SETTING: Deliveries in California in 2007. POPULATION: Term, singleton, vertex, nonanomalous deliveries among obese women (n = 74 725). METHODS: Women who underwent eIOL at 37 weeks were compared with women who were expectantly managed at that gestational age. Similar comparisons were made at 38, 39, and 40 weeks. Results were stratified by parity. Chi-square tests and multivariable logistic regression were used for statistical comparison. MAIN OUTCOME MEASURES: Method of delivery, severe perineal lacerations, postpartum haemorrhage, chorioamnionitis, macrosomia, shoulder dystocia, brachial plexus injury, respiratory distress syndrome. RESULTS: The odds of caesarean delivery were lower among nulliparous women with eIOL at 37 weeks [odds ratio (OR) 0.55, 95% confidence interval (CI) 0.34-0.90] and 39 weeks (OR 0.77, 95% CI 0.63-0.95) compared to expectant management. Among multiparous women with a prior vaginal delivery, eIOL at 37 (OR 0.39, 95% CI 0.24-0.64), 38 (OR 0.65, 95% CI 0.51-0.82), and 39 weeks (OR 0.67, 95% CI 0.56-0.81) was associated with lower odds of caesarean. Additionally, eIOL at 38, 39, and 40 weeks was associated with lower odds of macrosomia. There were no differences in the odds of operative vaginal delivery, lacerations, brachial plexus injury or respiratory distress syndrome. CONCLUSIONS: In obese women, term eIOL may decrease the risk of caesarean delivery, particularly in multiparas, without increasing the risks of other adverse outcomes when compared with expectant management. PMID- 26840781 TI - Case Report of Lichen Planopilaris Occurring in a Pediatric Patient Receiving a Tumor Necrosis Factor alpha Inhibitor and a Review of the Literature. AB - A 12-year-old girl with extended oligoarthritis treated with adalimumab presented with a short history of a progressive cutaneous eruption involving the legs and scalp. Physical examination and histologic results were consistent with lichen planopilaris. The adalimumab was discontinued. She received treatment with topical clobetasol propionate and the majority of the lesions resolved. Residual lesions and the extended oligoarthritis were then treated with sulfasalazine. Adalimumab is a tumor necrosis factor alpha (TNF-alpha) inhibitor used for the treatment of a variety of immunologically mediated conditions, including lichen planus and lichen planopilaris. TNF-alpha antagonists have been associated with paradoxical psoriasiform, lichenoid, eczematous, granulomatous, and acneiform eruptions. We detail this case and review the literature of lichenoid reactions secondary to TNF-alpha inhibitors. PMID- 26840783 TI - Diminished Splay Stiffening in Weak Gels of Calamitic-Bent-Core Nematic Composites. AB - Composites of calamitic and bent-core nematic molecules exhibiting a nematic to nematic-gel transformation have been investigated using thermal, electrical, X ray, and mechanical probes. The studies focusing on the Frank elastic behavior show a surprising result that the thermal behavior of the threshold voltage and the dependent splay elastic constant (K11) are remarkably different in temperature regions identified as weak and strong gels. In the former gel, the parameters exhibit values significantly smaller than the higher-temperature fluid nematic, effectively canceling out the underlying thermal variation due to the order parameter. This is especially attractive from the viewpoint of display devices. The X-ray diffraction data suggest that the fibers have a plastic nature in the weak gel and 3D-crystalline ordering in the strong gel. We argue that the different elastic behavior in the two gel phases is caused by the nature of the fibers; they are stiff in both gels but the interfiber interaction is weaker in the weak gel allowing the splay elastic constant to be lowered. The X-ray and rheological data lend support to the characterization of the fibers. PMID- 26840782 TI - Respiratory Viruses Associated Hospitalization among Children Aged <5 Years in Bangladesh: 2010-2014. AB - BACKGROUND: We combined hospital-based surveillance and health utilization survey data to estimate the incidence of respiratory viral infections associated hospitalization among children aged < 5 years in Bangladesh. METHODS: Surveillance physicians collected respiratory specimens from children aged <5 years hospitalized with respiratory illness and residing in the primary hospital catchment areas. We tested respiratory specimens for respiratory syncytial virus, parainfluenza viruses, human metapneumovirus, influenza, adenovirus and rhinoviruses using rRT-PCR. During 2013, we conducted a health utilization survey in the primary catchment areas of the hospitals to determine the proportion of all hospitalizations for respiratory illness among children aged <5 years at the surveillance hospitals during the preceding 12 months. We estimated the respiratory virus-specific incidence of hospitalization by dividing the estimated number of hospitalized children with a laboratory confirmed infection with a respiratory virus by the population aged <5 years of the catchment areas and adjusted for the proportion of children who were hospitalized at the surveillance hospitals. RESULTS: We estimated that the annual incidence per 1000 children (95% CI) of all cause associated respiratory hospitalization was 11.5 (10-12). The incidences per 1000 children (95% CI) per year for respiratory syncytial virus, parainfluenza, adenovirus, human metapneumovirus and influenza infections were 3(2-3), 0.5(0.4-0.8), 0.4 (0.3-0.6), 0.4 (0.3-0.6), and 0.4 (0.3-0.6) respectively. The incidences per 1000 children (95%CI) of rhinovirus-associated infections among hospitalized children were 5 (3-7), 2 (1-3), 1 (0.6-2), and 3 (2 4) in 2010, 2011, 2012 and 2013, respectively. CONCLUSION: Our data suggest that respiratory viruses are associated with a substantial burden of hospitalization in children aged <5 years in Bangladesh. PMID- 26840784 TI - Cross-sectoral cancer care: views from patients and health care professionals regarding a personal electronic health record. AB - Cross-sectoral cancer care is complex and involves collaboration from health care professionals (HCPs) across multiple sectors. However, when health information exchange (HIE) is not adequate, it results in impeded coordination and continuity of care. A web-based personal electronic health record (PEPA) under patients' control, providing access to personal health data across sectors, is being developed. Aim of this study was to explore perceived benefits and concerns. Using a qualitative approach, 10 focus groups were performed collecting views of three prospective user groups: patients with colorectal cancer (n = 12), physicians (n = 17) and other HCPs (n = 16). Representatives from different health sectors across the Rhine-Neckar region (Germany) participated. Data were audio- and videotaped, transcribed verbatim and thematically analysed. Our study shows that patients and HCPs expected a PEPA to enhance cross-sectoral availability of information, cross-sectoral cooperation and facilitate data management. Quality of cancer care was expected to be improved. Concerns were expressed in terms of data protection and data security. Concepts like a PEPA offer the chance to support HIE and avoid gaps of information in cross-sectoral cancer care. This may lead to improvements in coordination and continuity of care. Issues concerning data security and protection have to be addressed. PMID- 26840785 TI - Therapeutic plasma exchange for kidney transplantation: the problem of antibody mediated rejection. PMID- 26840786 TI - Patient blood management: where's the bottom? PMID- 26840787 TI - Splenic infarction and G-CSF. PMID- 26840790 TI - Impact of Socioeconomic Status and Ethnicity on Melanoma Presentation and Recurrence in Caucasian Patients. AB - OBJECTIVES: The impact of ethnicity and the socioeconomic status (SES) among Caucasians is not well studied. Here, we examine the impact of income on melanoma presentation and prognosis within a Caucasian cohort, accounting for ethnicity, as some reports suggest increased melanoma incidence in Ashkenazi Jewish (AJ) BRCA mutation carriers. METHODS: We studied prospectively enrolled primary melanoma patients at New York University. SES data were estimated using United States' Census Bureau data and patient zip codes. We evaluated associations between ethnicity, SES, and baseline characteristics using the chi2 test and multivariate logistic regression. We compared survival distributions using Kaplan Meier curves, log-rank tests, and Cox proportional hazard ratios. RESULTS: Of the 1,339 enrolled patients, AJ represented 32% (n = 423). Apart from AJ being older at presentation (p < 0.001), no significant differences were observed in baseline characteristics between ethnic groups. Patients with a median household income (MHI) lower than the median of the cohort were significantly more likely to present with advanced stages (p < 0.001) compared to patients with a higher MHI. Shorter overall (p = 0.016) and post-recurrence survival (p = 0.042) was also observed in patients from lower-income households. CONCLUSION: Data suggest that disparities in melanoma presentation in Caucasians stratify according to income independent of ethnic background. PMID- 26840791 TI - Green and Tunable Decoration of Graphene with Spherical Nanoparticles Based on Laser Ablation in Water: A Case of Ag Nanoparticle/Graphene Oxide Sheet Composites. AB - A simple and green strategy is presented to decorate graphene with nanoparticles, based on laser ablation of targets in graphene auqeous solution. Ag and graphene oxide (GO) are chosen as model materials. The surface of GO sheets is strongly anchored with spherical Ag nanoparticles. The density and size of the Ag nanoparticles can be easily tuned by laser ablation conditions. Further, the GO sheets can be decorated with other nanoparticles from simple metals or semiconductors to multicomponent hybrids. Additionally, the Ag nanoparticle/GO sheet colloids can be utilized as blocks to build three-dimensional structures, such as sandwich membranes by evaporation-induced self-assembly. These graphene based composite materials could be very useful in catalysis, sensors, and nanodevices. Particularly, the Ag nanoparticle/GO sheet sandwich composite membranes exhibit excellent surface-enhanced Raman scattering performance and possess the huge potential in trace-detecting persistent organic pollutants in the environment. PMID- 26840792 TI - Corneal fibrosarcoma in a cat. AB - PURPOSE: To present the clinicopathologic features of a Domestic Short-haired cat with spontaneous, intermediate-grade corneal fibrosarcoma, possibly secondary to chronic corneal irritation associated with a corneal sequestrum. METHODS: A 12 year-old, spayed female Domestic Short-haired cat was evaluated for a slowly growing, pink, exophytic mass affecting the left cornea. The cat had presented 6 years previously for bilateral brown corneal sequestra, as well as 3 years previously for a small pale growth on the left cornea hypothesized to be an epithelial inclusion cyst and a corneal ulcer affecting the right eye. Incisional biopsy of the corneal mass indicated intermediate-grade corneal fibrosarcoma within the corneal stroma. Owing to the potential for malignant behavior, the left globe was enucleated. Routine systemic staging was performed prior to surgery with no evidence of metastasis. RESULTS: Definitive diagnosis of corneal fibrosarcoma was made through histopathologic examination of the incisional biopsy. There was an elevated mitotic index, indicating an intermediate-grade phenotype. Histopathology of the enucleated globe substantiated the initial findings, and complete tumor resection was confirmed. Subjacent to the corneal fibrosarcoma, there was a region of necrotic tissue suggestive of a corneal sequestrum. Six months after diagnosis and enucleation, the patient remained healthy with no signs of local spread or distant metastasis. CONCLUSIONS: To the authors' knowledge, this is the first documented case of a corneal fibrosarcoma in a cat. PMID- 26840793 TI - Negotiated autonomy in diabetes self-management: the experiences of adults with intellectual disability and their support workers. AB - BACKGROUND: The basic human right of autonomy is underpinned by the ability to practice decision-making. The rights of people with disabilities to engage in autonomous decision-making are promoted as best practice and includes decisions around health and self-care. Little is known about autonomy in the field of long term condition management. This paper explores how people with intellectual disabilities (ID) and their support workers experience and practice autonomy in relation to the management of diabetes. METHODS: Semi-structured interviews were completed in residential and independent living settings with people living with an ID and type 1 (N = 8) or type 2 (N = 6) diabetes and their support workers (N = 17). The participant with ID's support worker was present as requested; however, the interviews were run separately with each participant rather than jointly. Thematic analysis was undertaken, and a constructivist lens informed both data collection and analysis. RESULTS: The analysis revealed a strong process of negotiated autonomy between people with ID and their support workers in relation to the daily management of diabetes. During times of transition, roles in relation to diabetes management were renegotiated, and the promotion of autonomy was prefaced within the context of risk and client safety. Goals to increase independence were drivers for negotiating greater autonomy. CONCLUSIONS: The successful negotiation of autonomy in relation to diabetes illustrates the potential for people with ID to play a key role in the management of long-term health conditions. The study highlights the primacy of developing decision-making skills among people with ID. Promoting opportunities for decision-making and an ethos of supported decision-making through person-centred planning are all vital in working towards enhancing autonomy. PMID- 26840795 TI - The Unique Dermoscopic Structure 'Large black web' in basal cell carcinoma on the areola. PMID- 26840794 TI - Protein tyrosine phosphatase 1B dephosphorylates PITX1 and regulates p120RasGAP in hepatocellular carcinoma. AB - The effective therapeutic targets for hepatocellular carcinoma remain limited. Pituitary homeobox 1 (PITX1) functions as a tumor suppressor in hepatocarcinogenesis by regulating the expression level of Ras guanosine triphosphatase-activating protein. Here, we report that protein tyrosine phosphatases 1B (PTP1B) directly dephosphorylated PITX1 at Y160, Y175, and Y179 to further weaken the protein stability of PITX. The PTP1B-dependent decline of PITX1 reduced its transcriptional activity for p120RasGAP (RASA1), a Ras guanosine triphosphatase-activating protein. Both silencing of PTP1B and PTP1B inhibitor up-regulated the PITX1-p120RasGAP axis through hyperphosphorylation of PITX1. Sorafenib, the first and only targeted drug approved for hepatocellular carcinoma, directly decreased PTP1B activity and promoted the expression of PITX1 and p120RasGAP by PITX1 hyperphosphorylation. Molecular docking also supported the potential interaction between PTP1B and sorafenib. PTP1B overexpression impaired the sensitivity of sorafenib in vitro and in vivo, implying that PTP1B has a significant effect on sorafenib-induced apoptosis. In sorafenib-treated tumor samples, we further found inhibition of PTP1B activity and up-regulation of the PITX1-p120RasGAP axis, suggesting that PTP1B inhibitor may be effective for the treatment of hepatocellular carcinoma. By immunohistochemical staining of hepatic tumor tissue from 155 patients, the expression of PTP1B was significantly in tumor parts higher than nontumor parts (P = 0.02). Furthermore, high expression of PTP1B was significantly associated with poor tumor differentiation (P = 0.031). CONCLUSION: PTP1B dephosphorylates PITX1 to weaken its protein stability and the transcriptional activity for p120RasGAP gene expression and acts as a determinant of the sorafenib-mediated drug effect; targeting the PITX1 p120RasGAP axis with a PTP1B inhibitor may provide a new therapy for patients with hepatocellular carcinoma. PMID- 26840797 TI - CJD: Understanding Creutzfeldt-Jakob disease. AB - Rare, transmissible, and rapidly progressive, Creutzfeldt-Jakob disease (CJD) is an ultimately fatal central nervous system infection caused by accumulation of abnormally shaped prion proteins in neurons (see Understanding prion proteins). Although categorized as an infection, CJD doesn't lead to the immune system or inflammatory response typical of most infectious diseases. This article discusses the pathophysiology and diagnosis of this terminal illness and nursing care for patients with suspected or confirmed CJD. PMID- 26840798 TI - What's new in nutrition for adults with diabetes? PMID- 26840796 TI - [6]-Shogaol, a Novel Chemopreventor in 7,12-Dimethylbenz[a]anthracene-induced Hamster Buccal Pouch Carcinogenesis. AB - Oral cancer is a major cause of morbidity and mortality in developing countries. Despite advances in chemotherapy for the cancer management, the survival rate has not yet been improved. Dietary nutrient has been receiving a lot of attention and interest in the chemotherapeutic development. [6]-Shogaol is a major bioactive compound identified in ginger that possesses many pharmacological properties. The aim of the present study is to investigate the effect of [6]-shogaol on 7,12 dimethylbenz[a]anthracene-induced hamster buccal pouch (HBP) carcinogenesis. Oral squamous cell carcinoma induced in HBP by painting with 0.5% 7,12 dimethylbenz(a)anthracene (DMBA), thrice in a week for 16 weeks. We observed 100% tumour incidence, decreased levels of lipid peroxidation, antioxidant, and phase II detoxification enzymes (GST, GR and GSH) in DMBA-induced hamsters. Further, enhanced activity of phase I enzymes (cytochrome p450 and b5) and over-expression of mutant p53, Bcl-2 and decreased expression of wild type p53 and Bax were noticed in DMBA-induced hamsters. Our results indicated that [6]-shogaol (10, 20 and 40 mg/kg body weight) treated with DMBA-painted hamsters, considerably reversed tumour incidence, improved antioxidant status, phase II detoxification enzymes, and also inhibit lipid peroxidation and phase I enzymes. Moreover, [6] shogaol inhibits mutant p53 and Bcl-2 expression and significantly restored normal p53, Bax levels. Thus, we concluded that [6]-shogaol prevents DMBA-induced HBP carcinogenesis through its antioxidant as well as modulating apoptotic signals. PMID- 26840799 TI - Prediction of Rate Constant for Supramolecular Systems with Multiconfigurations. AB - The control of supramolecular systems requires a thorough understanding of their dynamics, especially on a molecular level. It is extremely difficult to determine the thermokinetic parameters of supramolecular systems, such as drug-cyclodextrin complexes with fast association/dissociation processes by experimental techniques. In this paper, molecular modeling combined with novel mathematical relationships integrating the thermodynamic/thermokinetic parameters of a series of isomeric multiconfigurations to predict the overall parameters in a range of pH values have been employed to study supramolecular dynamics at the molecular level. A suitable form of Eyring's equation was derived and a two-stage model was introduced. The new approach enabled accurate prediction of the apparent dissociation/association (k(off)/k(on)) and unbinding/binding (k-r/kr) rate constants of the ubiquitous multiconfiguration complexes of the supramolecular system. The pyronine Y (PY) was used as a model system for the validation of the presented method. Interestingly, the predicted k(off) value ((40 +/- 1) * 10(5) s(-1), 298 K) of PY is largely in agreement with that previously determined by fluorescence correlation spectroscopy ((5 +/- 3) * 10(5) s(-1), 298 K). Moreover, the k(off)/k(on) and k-r/kr for flurbiprofen-beta-cylcodextrin and ibuprofen-beta cyclodextrin systems were also predicted and suggested that the association processes are diffusion-controlled. The methodology is considered to be especially useful in the design and selection of excipients for a supramolecular system with preferred association and dissociation rate constants and understanding their mechanisms. It is believed that this new approach could be applicable to a wide range of ligand-receptor supramolecular systems and will surely help in understanding their complex mechanism. PMID- 26840801 TI - Physical Activity and Insomnia, Short Sleep and Insulin Resistance, and Effect of Poor Sleep on Children's Academic Performance. PMID- 26840800 TI - New insights into FtsZ rearrangements during the cell division of Escherichia coli from single-molecule localization microscopy of fixed cells. AB - FtsZ - a prokaryotic tubulin homolog - is one of the central components of bacterial division machinery. At the early stage of cytokinesis FtsZ forms the so called Z-ring at mid-cell that guides septum formation. Many approaches were used to resolve the structure of the Z-ring, however, researchers are still far from consensus on this question. We utilized single-molecule localization microscopy (SMLM) in combination with immunofluorescence staining to visualize FtsZ in Esherichia coli fixed cells that were grown under slow and fast growth conditions. This approach allowed us to obtain images of FtsZ structures at different stages of cell division and accurately measure Z-ring dimensions. Analysis of these images demonstrated that Z-ring thickness increases during constriction, starting at about 70 nm at the beginning of division and increasing by approximately 25% half-way through constriction. PMID- 26840802 TI - Therapeutic options in neuromyelitis optica spectrum disorders. AB - Neuromyelitis optica is a relapsing inflammatory disorder of the central nervous system that manifests predominantly with attacks of optic neuritis and longitudinally extensive transverse myelitis; attacks are often severe. In contrast to multiple sclerosis, a secondary progressive phase is rare, and disability in neuromyelitis optica spectrum disorders is related to relapses. Thus, prompt and effective treatment of relapses, and early initiation of long term immunosuppression to prevent subsequent attacks is required in order to prevent morbidity and mortality. PMID- 26840803 TI - Soil carbon and nitrogen stocks in forests along an altitudinal gradient in the eastern Himalayas and a meta-analysis of global data. AB - High-altitude soils potentially store a large pool of carbon (C) and nitrogen (N). The assessment of total C and N stocks in soils is vital to understanding the C and N dynamics in terrestrial ecosystems. In this study, we examined effects of altitude and forest composition on soil C and N along a transect from 317 to 3300 m a.s.l. in the eastern Himalayas. We used meta-analysis to establish the context for our results on the effects of altitude on soil C, including variation with depth. Total C and N contents of soils significantly increased with altitude, but decreased with soil depth. Carbon and N were similarly correlated with altitude and temperature, and temperature was seemingly the main driver of soil C along the altitudinal gradient. Altitude accounted for 73% of the variation in C and 47% of the variation in N stocks. Soil pH and cation exchange capacity were correlated with both soil C and N stocks. Increases in soil C and N stocks were related to forest composition, forest basal area as well as quantity of leaf litter that were in turn influenced by altitude and temperature. Concentrations of C in foliage increased by 2.1% for every 1000 m rise in altitude, while that in leaf litter increased by 2.3%. PMID- 26840804 TI - Karyoevolution in Potamorhina (Cope, 1878) (Ostariophysi, Curimatidae): Using Repetitive DNA for the Elucidation of Genome Organization. AB - Some families of Characiformes present the tendency toward stability of the karyotypic macrostructure as Curimatidae, which contains species with a 2n = 54 karyotype and metacentric and submetacentric chromosomes, however, some Potamorhina species contradict to this tendency. Some species of the central Amazon exhibit different diploid number and show intraspecific variation in the location of heterochromatin. By performing cytogenetic characterization by localization of heterochromatin and the nucleolus organizer region, as well as physical chromosome mapping using probes targeting 5S and 18S ribosomal DNA (rDNA), retroelement of Xiphophorus 1 (Rex1), Rex3, telomeres, and tropomyosin 1 (TPM1), we attempted to understand the evolutionary mechanisms involved in the differentiation of the Potamorhina species. The analyses showed that the heterochromatic regions of the examined species are distinct and transposable elements are involved in this evolutionary process, considering that the dynamic regions of the genome appear to include the terminal regions and particularly the heterochromatin-rich centromeric regions, which are involved in fission and fusion processes and promote the differentiation of chromosome pairs that bear ribosomal sites; these pairs were similar in the central Amazon species. Thus, we propose a phylogeny for this genus. PMID- 26840805 TI - Study of Heat Transfer Dynamics from Gold Nanorods to the Environment via Time Resolved Infrared Spectroscopy. AB - Studying the local solvent surrounding nanoparticles is important to understanding the energy exchange dynamics between the particles and their environment, and there is a need for spectroscopic methods that can dynamically probe the solvent region that is in nearby contact with the nanoparticles. In this work, we demonstrate the use of time-resolved infrared spectroscopy to track changes in a vibrational mode of local water on the time scale of hundreds of picoseconds, revealing the dynamics of heat transfer from gold nanorods to the local water environment. We applied this probe to a prototypical plasmonic photothermal system consisting of organic CTAB bilayer capped gold nanorods, as well as gold nanorods coated with varying thicknesses of inorganic mesoporous silica. The heat transfer time constant of CTAB capped gold nanorods is about 350 ps and becomes faster with higher laser excitation power, eventually generating bubbles due to superheating in the local solvent. Silica coating of the nanorods slows down the heat transfer and suppresses the formation of superheated bubbles. PMID- 26840806 TI - Information and communication technologies and new forms of sociability: possibilities and challenges for Public Health. PMID- 26840807 TI - Dilemmas and challenges for implementing global mental health policies in Brazil. PMID- 26840808 TI - Assessment of participation bias in cohort studies: systematic review and meta regression analysis. AB - The proportion of non-participation in cohort studies, if associated with both the exposure and the probability of occurrence of the event, can introduce bias in the estimates of interest. The aim of this study is to evaluate the impact of participation and its characteristics in longitudinal studies. A systematic review (MEDLINE, Scopus and Web of Science) for articles describing the proportion of participation in the baseline of cohort studies was performed. Among the 2,964 initially identified, 50 were selected. The average proportion of participation was 64.7%. Using a meta-regression model with mixed effects, only age, year of baseline contact and study region (borderline) were associated with participation. Considering the decrease in participation in recent years, and the cost of cohort studies, it is essential to gather information to assess the potential for non-participation, before committing resources. Finally, journals should require the presentation of this information in the papers. PMID- 26840809 TI - Interactions among stakehoklders involved in return to work after sick leave due to mental disorders: a meta-ethnography. AB - Mental disorders cause impact in the work environment. Investigations of interaction among stakeholders who are involved in the return to work are scarce. Meta-ethnography serves to synthesize qualitative studies by means of ongoing interpretation and comparison of the ideas presented in the articles. The goal of this study is to present a meta-ethnography of the interactions among the stakeholders involved in the return to work process after leave of absence due to mental disorders. It aims: (1) to investigate the interactions among stakeholders involved in return to work; (2) to identify enablers or obstacles for the return to work. The database search found 619 articles, 16 of which met the inclusion criteria. Analysis of the articles revealed six second-order concepts that resulted in two syntheses. The first is about performance ethos in the return to work, and the second shows return to work as a catalyst of new life styles. Models that favor the worker's performance ethos, as well as a perspective oriented by psychosocial aspects may enable return to work practices after leave of absence due to mental disorders. PMID- 26840810 TI - [Psychometric evaluation of the Body Change Questionnaire for adolescents]. AB - This study aimed to examine construct validity, internal consistency, and reproducibility of the Body Change Questionnaire (BCQ). A total of 439 female and male adolescents (13-22 years of age) were evaluated. Construct validity was assessed by exploratory factor analysis and correlation between the scores of the BCQ and the Body Shape Questionnaire (BSQ) and Scale Silhouettes (SS). Reliability was assessed through internal consistency and reproducibility using test-retest and intra-class correlation. The scale presented a six-factor structure that almost entirely accounted for the instrument's subscales. Correlations for the total sample between BCQ and scores of the other questionnaires ranged from 0.37 to 0.46. Internal consistency varied from 0.78 to 0.96 for each of the factors, and intra-class correlation was consistent with good reproducibility. The test-retest scores showed no statistically significant differences for the total sample or according to sex. The BCQ showed good psychometric qualities for Brazilian adolescents. PMID- 26840811 TI - Cruising and e-dates: a new context for sexual encounters among young men who have sex with men. AB - This article addresses the rapidly growing use of information and communication technologies in mediating new settings for sexual relations. The specific focus is on cruising among young men who have sex with men via e-dating. The study used a qualitative methodology with peer group discussions on sexuality, health, and risk. The new framework provided by technology is marked by (a) increased access to these practices, (b) greater dissemination of them, (c) greater immediacy of encounters, (d) anticipation of what will be offered during dates, (e) anonymous access, allowing bolder proposals, and (f) openness to a wider range of users. These elements converge in a framework that indicates a new social organization of sexual practice. PMID- 26840812 TI - Characteristics of adverse events in primary health care in Brazil. AB - This study aimed to evaluate the occurrence of incidents in primary health care in Brazil. Fifteen health professionals working in Family Health Strategy units agreed to anonymously and confidentially record incidents over the course of five months, using the questionnaire Primary Care International Study of Medical Errors (PCISME) questionnaire adapted to the Brazilian context. The overall rate of incidents was 1.11%. The rate of incidents that did not reach patients was 0.11%. The rate of incidents reaching patients but without causing harm was 0.09%. The rate of incidents reaching patients and causing adverse events was 0.9%. Eight types of most frequent errors and administrative failures were identified. Communication failures were the most common contributing factor to incidents in primary health care (53%). The findings show that incidents occur in primary health care (as elsewhere in the health system), but research in this area is still incipient. PMID- 26840813 TI - [The influence of excess weight and obesity on health spending in Brazilian households]. AB - The objective of this study was to evaluate the influence of excess weight and obesity on health spending in Brazilian households. Data from the Household Budget Survey 2008-2009 were used to estimate monetary health spending, corresponding to out-of-pocket spending, including purchase of medicines and payment for healthcare services, and to evaluate the nutritional status of the 55,970 household residents. Monthly spending on health and its components were analyzed according to the number of excess weight and obese individuals in households (none, one, two, or three or more individuals). The presence and increasing number of excess weight and obese individuals has resulted in greater spending on health, especially on medicines and health insurance. The results were maintained after adjusting for income, region, area, and presence of elderly and number of residents in the household. Excess weight and obesity had a direct impact on out-of-pocket health spending by Brazilian families. PMID- 26840814 TI - Lay perceptions of health and environmental inequalities and their associations to mental health. AB - Health inequalities are very well documented in epidemiological research: rich people live longer and have fewer diseases than poor people. Recently, a growing amount of evidence from environmental sciences confirms that poor people are also more exposed to pollution and other environmental threats. However, research in the social sciences has shown a broad lack of awareness about health inequalities. In this paper, based on data collected in Portugal, we will analyze the consciousness of both health and environmental injustices and test one hypothesis for this social blindness. The results show, even more clearly than before, that public opinion tends to see rich and poor people as being equally susceptible to health and environmental events. Furthermore, those who have this equal view of the world present lower levels of depression and anxiety. Following cognitive adaptation theory, this "belief in an equal world" can be interpreted as a protective positive illusion about social justice, particularly relevant in one of the most unequal countries in Europe. PMID- 26840815 TI - [Socioeconomic conditions, physician supply, and ambulatory care sensitive hospitalization in large Brazilian cities]. AB - Ambulatory care sensitive hospitalizations have been used as an indicator of the effectiveness of primary health care. The research involved a descriptive analysis of the evolution of national indicators from 1998 to 2012 and a cross sectional study of Brazilian municipalities with populations greater than 50,000, by region of the country, for the year 2012, using correlation and linear regression statistical techniques. There was a slight decline in the proportion of ambulatory care sensitive hospitalizations in Brazil. Socioeconomic and demographic factors and physician supply in the healthcare system are associated with the proportion of ambulatory care sensitive hospitalizations, differing by region of the country. Despite advances in the expansion of the Family Health Strategy, some challenges remain, including better distribution of physicians and other health professionals in the country and effective changes in the healthcare model. PMID- 26840816 TI - Socioeconomic and environmental determinants of adolescent asthma in urban Latin America: an ecological analysis. AB - The prevalence of asthma is high in urban areas of many Latin-American countries where societies show high levels of inequality and different levels of development. This study aimed to examine the relationship between asthma symptoms prevalence in adolescents living in Latin American urban centers and socioeconomic and environmental determinants measured at the ecological level. Asthma prevalence symptoms were obtained from the International Study of Asthma and Allergies in Childhood (ISAAC) phase III. A hierarchical conceptual framework was defined and the explanatory variables were organized in three levels: distal, intermediate, proximal. Linear regression models weighed by sample size were undertaken between asthma prevalence and the selected variables. Asthma prevalence was positively associated with Gini index, water supply and homicide rate, and inversely associated with the Human Development Index, crowding and adequate sanitation. This study provides evidence of the potential influence of poverty and social inequalities on current wheezing in adolescents in a complex social context like Latin America. PMID- 26840817 TI - [Analysis of the implementation of the TeleHealth Program in Pernambuco State, Brazil: a case study]. AB - The Network of TeleHealth Centers (RedeNutes) is part of the TeleHealth Brazil Program and conducts activities for the Family Health Strategy through the telecare and teleeducation services. The objective of this study was to evaluate the degree of implementation of RedeNutes in six municipalities (counties) in Pernambuco State. This was an evaluation study analyzing implementation in the second component, referring to analysis of the impact of implementation on the observed effects, backed by the multiple case study strategy. The analysis involved the manager, municipal, and global dimensions and their components: planning, development, portal, telecare, and teleeducation. In the Manager dimension, the degree of implementation was considered implemented; in the Municipal and Global dimensions, partially implemented; in the TeleCare component it was not implemented. In conclusion, TeleHealth can help improve comprehensive healthcare for the assisted population, but it requires overcoming problems with adherence to the intervention, especially in TeleCare. PMID- 26840818 TI - [Factors associated with late initiation of breastfeeding in the Brazilian Unified National Health System in the city of Rio de Janeiro, Brazil, 2009]. AB - This study aimed to analyze factors associated with delayed initiation of breastfeeding (lack of breastfeeding in the first hour of life). This was a cross sectional study conducted in 2009 with 673 postpartum women at hospitals belonging to the Brazilian Unified National Health System (SUS) in the city of Rio de Janeiro, Brazil. Statistical analysis used multilevel logistic regression, with two levels (individual and hospital). Prevalence of delayed initiation of breastfeeding was 49.2%. Delivery in a Baby-Friendly Hospital (BFH) had a protective effect against late initiation of breastfeeding (OR = 0.17; 95%CI: 0.05-0.55), while cesarean section (OR = 5.95; 95%CI: 3.88-9.12) and ignorance of HIV status until delivery (OR = 2.16; 95%CI: 1.04-4.50) increased the odds of delay. Reduction in cesarean rates, adherence to protocols to prevent vertical HIV transmission, and expanded accreditation of hospitals in the BFH are important strategies to promote breastfeeding in the first hour of life. PMID- 26840819 TI - [Use of potentially inappropriate medications in the elderly in Vicosa, Minas Gerais State, Brazil: a population-based survey]. AB - The study evaluated the use of potentially inappropriate medications among elderly in Vicosa, Minas Gerais State, Brazil, according to the Beers 2012 and STOPP criteria, as well as factors associated with this use. This was a cross sectional study of 621 community-dwelling elderly using home interviews. The explanatory variables were gender, age, education, self-rated health, restriction of activities in the previous 15 days, functional capacity, history of hospital admission, number of self-reported diseases, and polypharmacy. Multivariate Poisson regression was used. There was a high prevalence of potentially inappropriate medications according to the Beers 2012 and STOPP criteria: 43.8% (95%CI: 37.8%-47.8%) and 44.8% (95%CI: 40.9%-48.8%), respectively. Female gender and polypharmacy remained independently associated with use of potentially inappropriate medications according to the Beers criteria. As for the STOPP criteria, the variables independently associated with use of potentially inappropriate medications were female gender, fair self-rated health, and polypharmacy. Efforts are needed to upgrade polypharmacy in Brazilian elders. PMID- 26840820 TI - [Social inequalities influence the quality and diversity of diet in Brazilian children 6 to 36 months of age]. AB - The objective of this study was to assess dietary patterns in Brazilian children and factors associated with better diet. The authors used data for 2,477 children 6 to 36 months of age from the Brazilian National Survey of Demographic and Health in 2006-2007. Diet was assessed and classified using a composite index. The results showed that 28.2% of the children received a high-quality diet and 20% had a diversified diet. Children from socioeconomically underprivileged families or with serious food insecurity were approximately 40% less likely to have high-quality diets. Children living in homes with food insecurity were 71% less likely to have diversified diets, and those whose mothers had limited education were 43% less likely. Children residing in the North of Brazil were less likely to have diversified and high-quality diets. The dietary quality of Brazilian children is inadequate, and social vulnerability is closely associated with this adverse dietary situation. PMID- 26840822 TI - [Effect of waiting time for radiotherapy on five-year overall survival in women with cervical cancer, 1995-2010]. AB - Overall 5-year survival and factors associated with death were evaluated in a cohort of 342 women with cervical cancer referred to radiotherapy in the Baixada Fluminense, in Greater Metropolitan Rio de Janeiro State, Brazil. Overall 5-year survival was 25.3%, reaching 60.8% in women with stage IIA or less. The model adjusted by extended Cox proportional regression showed an increase in mortality risk for patients with stages IIB-IIIB (HR = 1.89; 95%CI: 1.214; 2.957) and IVA IVB (HR = 5.78; 95%CI: 2.973; 11.265). Cytology in asymptomatic women (HR = 0.58; 95%CI: 0.362; 0.961) and referral for first consultation in an oncology service in the Baixada Fluminense (HR = 0.60; 95%CI: 0.418; 0.875) were the main protective factors identified by the study. Waiting time (> 60 versus <= 60 days) was not statistically significant, but a delay of 4 days worsened the outcome. The 60-day limit for initiating radiotherapy should be respected, because delay greater than 64 days showed a significant association between all waiting time cut-off points and 5-year mortality risk. PMID- 26840821 TI - Periodontal conditions and associated factors among adults and the elderly: findings from the first National Oral Health Survey in Uruguay. AB - The aims of this study were to assess the prevalence of periodontal conditions in the Uruguayan adult and elderly population and its association with socioeconomic and behavioral characteristics. Data from adults (35-44, n = 358) and elderly (65 74, n = 411) who participated in the first National Oral Health Survey, Uruguay, 2011, were used. The survey included a household questionnaire addressing socioeconomic characteristics, and tobacco use. Bleeding on probing (BOP), periodontal pockets (CPI) and clinical attachment loss (CAL) were measured by clinical examination. A multivariable analysis was carried out. Considering both age groups, the prevalence of mild/severe periodontal disease was 21.8% and 9.12% for severe periodontal disease. Adjusted analyses revealed an association between high education and all outcomes. Attendance at dental services was negatively associated with BOP and mild to severe periodontitis. Periodontal outcomes were higher in disadvantaged socioeconomic groups. Tobacco consumption has a strong association with periodontal disease in the elderly. PMID- 26840823 TI - [Inequalities in self-rated health: an analysis of the Brazilian and Portuguese populations]. AB - The aim of this study was to analyze the prevalence of poor self-rated health according to socio-demographic variables and the presence of chronic diseases in the populations of Brazil and Portugal. A total of 13,894 individuals >= 30 years of age were studied in capitals in Northeast Brazil (VIGITEL 2011) and 20,579 in Portugal (4th NHI, 2005/2006). Poisson regression was used in both analyses of associations, adjusted by covariates. Net prevalence rates of poor health in men in Northeast Brazil and Portugal were 4.3% and 15.5%. Prevalence ratio was 2.72 (95%CI: 2.70-2.75) after standardization by age bracket. In women, prevalence was 8.1% in Northeast Brazil and 25.1% in Portugal (PR: 2.40; 95%CI: 2.39-2.42). The variable that showed the worst inequalities in poor self-rated health was schooling, in both Brazil and Portugal. Current disease had a stronger effect on Brazilians than on Portuguese, in both men and women. Prevalence of poor self rated health was significantly higher in Portugal in all the groups analyzed. PMID- 26840824 TI - [ERRATA]. PMID- 26840825 TI - [ERRATA]. PMID- 26840826 TI - Light at the End of the Protein: Crystal Structure of a C-Terminal Light-Sensing Domain. AB - Aureochromes are blue light sensors that act as transcription factors in algae and have been repurposed for the optogenetic control of signaling in mammalian cells. In a recent issue of Structure, Banerjee et al. (2016) shine light on the structure and function of the C-terminal light-sensing domain of Phaeodactylum tricornutum aureochrome1. PMID- 26840827 TI - Safeguarding Structural Data Repositories against Bad Apples. AB - Structural biology research generates large amounts of data, some deposited in public databases or repositories, but a substantial remainder never becomes available to the scientific community. In addition, some of the deposited data contain less or more serious errors that may bias the results of data mining. Thorough analysis and discussion of these problems is needed to ameliorate this situation. This perspective is an attempt to propose some solutions and encourage both further discussion and action on the part of the relevant organizations, in particular the PDB and various bodies of the International Union of Crystallography. PMID- 26840829 TI - Targeting oliguria reversal in perioperative restrictive fluid management does not influence the occurrence of renal dysfunction: A systematic review and meta analysis. AB - BACKGROUND: Interest in perioperative fluid restriction has increased, but it could lead to hypovolaemia. Urine output is viewed as a surrogate for renal perfusion and is frequently used to guide perioperative fluid therapy. However, the rationale behind targeting oliguria reversal - achieving and maintaining urine output above a previously defined threshold by additional fluid boluses - is often questioned. OBJECTIVE: We assessed whether restrictive fluid management had an effect on oliguria, acute renal failure (ARF) and fluid intake. We also investigated whether targeting oliguria reversal affected these parameters. DESIGN: Systematic review of randomised controlled trials with meta-analyses. We used the definitions of restrictive and conventional fluid management as provided by the individual studies. DATA SOURCES: We searched MEDLINE (1966 to present), EMBASE (1980 to present), and relevant reviews and articles. ELIGIBILITY CRITERIA: We included randomised controlled trials with adult patients undergoing surgery comparing restrictive fluid management with a conventional fluid management protocol and also reporting the occurrence of postoperative ARF. RESULTS: We included 15 studies with a total of 1594 patients. There was insufficient evidence to associate restrictive fluid management with an increase in oliguria [restrictive 83/186 vs. conventional 68/230; odds ratio (OR) 2.07; 95% confidence interval (CI), 0.97 to 4.44; P = 0.06; I = 23.7%; Nstudies = 5]. The frequency of ARF in restrictive and conventional fluid management was 20/795 and 20/799, respectively (OR 1.07; 95% CI, 0.60 to 1.92; P = 0.8; I = 17.5%; Nstudies = 15). There was no statistically significant difference in ARF occurrence between studies targeting oliguria reversal and not targeting oliguria reversal (OR 0.31; 95% CI, 0.08 to 1.22; P = 0.088). Intraoperative fluid intake was 1.89 l lower in restrictive than in conventional fluid management when not targeting oliguria reversal (95% CI, -2.59 to -1.20 l; P < 0.001; I = 96.6%; Nstudies = 7), and 1.63 l lower when targeting oliguria reversal (95% CI, -2.52 to -0.74 l; P < 0.001; I = 96.6%; Nstudies = 6). CONCLUSION: Our data suggest that, even though event numbers are small, perioperative restrictive fluid management does not increase oliguria or postoperative ARF while decreasing intraoperative fluid intake, irrespective of targeting reversal of oliguria or not. PMID- 26840830 TI - Incidence of general anaesthesia for caesarean section in parturients from different geographic regions: 7-year retrospective study in a single European university centre. PMID- 26840828 TI - Autoantibodies to Heat-Shock Protein, HSPA5, and Epitope Spreading: High-Dose Dexamethasone Therapy Rescues Ovarian Function in Experimental Autoimmune Ovarian Insufficiency Mouse Model. AB - PROBLEM: Role of autoantibodies to heat-shock protein 70 isoform, HSPA5, both alone or in combination with other antigenic peptides in epitope spreading and effect of high-dose dexamethasone to overcome this. METHOD OF STUDY: Experimental autoimmune premature ovarian insufficiency mouse model generated by immunization with immunodominant epitopes of HSPA5 alone or in combination with other antigenic peptides. Two doses of dexamethasone treatment are given to the latter group. Immunosorbent assay and Western blot analysis were undertaken to detect cross-reactivity. Hormonal estimations, histological evaluation, and fertility studies were performed to assess treatment efficacy. RESULTS: One of the immunodominant epitopes of HSPA5 led to epitope spreading. Of the two doses, 100 mg was more effective in rescuing fertility. CONCLUSIONS: We postulate that the shared immunodominant peptide could be included in a peptide array to detect both HSAP5 and HSP90beta autoantibodies for early diagnosis or prognosis of aPOI and customized glucocorticoid therapy for such subjects. PMID- 26840831 TI - The Effect of Divergence in Feed Efficiency on the Intestinal Microbiota and the Intestinal Immune Response in Both Unchallenged and Lipopolysaccharide Challenged Ileal and Colonic Explants. AB - Feed efficiency is an important trait in pig production, with evidence to suggest that the efficiencies of a variety of biological systems contribute to variation in this trait. Little work has been conducted on the contribution of the intestinal innate immune response to divergence in feed efficiency. Hence, the objective of this study was to examine select bacterial populations and gene expression profiles of a range of targets relating to gut health and immunity in the intestine of pigs phenotypically divergent in feed efficiency in: a) the basal state; and (b) following an ex-vivo lipopolysaccharide (LPS) challenge of ileal and colonic tissue. Male pigs (initial BW 22.4 kg (SD = 2.03)) were fed a standard finishing diet for the final 43 days prior to slaughter to evaluate feed intake and growth for the purpose of calculating residual feed intake (RFI). On day 115, 16 animals (average weight 85 kg, SEM 2.8 kg), designated high RFI (HRFI) and low RFI (LRFI) were slaughtered. The LRFI pigs had increased lactobacillus spp. in the caecum compared to HRFI pigs (P < 0.05). RFI groups did not differ in the expression of the measured genes involved in the innate immune system in the basal ileal or colonic tissues (P > 0.10). Interestingly, there was an interaction between RFI and LPS for the cytokines IL-8, IL-1, IL-6, TNF-alpha, Interferon-gamma (IFN-gamma) and SOCS3, with the LRFI group having consistently lower gene expression in the colon following the LPS challenge, compared to the HRFI group. The lower gene expression of SOCS and cytokines following an ex vivo LPS challenge supports the theory that a possible energy saving mechanism exists in the intestinal innate immune response to an immune challenge in more feed efficient pigs. PMID- 26840833 TI - Open-Shell Phenalenyl in Transition Metal-Free Catalytic C-H Functionalization. AB - Open-shell phenalenyl chemistry has widely been explored in the last five decades demonstrating its potential in various applications including molecular switch, spin memory device, molecular battery, cathode material, etc. In this article, we have explored another new direction of open-shell phenalenyl chemistry toward transition metal-free catalytic C-H functionalization process. A phenalenyl ligand, namely, 9-methylamino-phenalen-1-one (4a), promoted chelation-assisted single electron transfer (SET) process, which facilitates the C-H functionalization of unactivated arenes to form the biaryl products. The present methodology offers a diverse substrate scope, which can be operated without employing any dry or inert conditions and under truly transition metal based catalyst like loading yet avoiding any expensive or toxic transition metal. This not only is the first report on the application of phenalenyl chemistry in C-H functionalization process but also provides a low-catalyst loading organocatalytic system (up to 0.5 mol % catalyst loading) as compared to the existing ones (mostly 20-40 mol %), which has taken advantage of long known phenalenyl based radical stability through the presence of its low-lying nonbonding molecular orbital. PMID- 26840832 TI - A Novel Selectable Islet 1 Positive Progenitor Cell Reprogrammed to Expandable and Functional Smooth Muscle Cells. AB - Disorders affecting smooth muscle structure/function may require technologies that can generate large scale, differentiated and contractile smooth muscle cells (SMC) suitable for cell therapy. To date no clonal precursor population that provides large numbers of differentiated SMC in culture has been identified in a rodent. Identification of such cells may also enhance insight into progenitor cell fate decisions and the relationship between smooth muscle precursors and disease states that implicate differentiated SMC. In this study, we used classic clonal expansion techniques to identify novel self-renewing Islet 1 (Isl-1) positive primitive progenitor cells (PPC) within rat bone marrow that exhibited canonical stem cell markers and preferential differentiation towards a smooth muscle-like fate. We subsequently used molecular tagging to select Isl-1 positive clonal populations from expanded and de novo marrow cell populations. We refer to these previously undescribed cells as the PPC given its stem cell marker profile, and robust self-renewal capacity. PPC could be directly converted into induced smooth muscle cells (iSMC) using single transcription factor (Kruppel-like factor 4) knockdown or transactivator (myocardin) overexpression in contrast to three control cells (HEK 293, endothelial cells and mesenchymal stem cells) where such induction was not possible. iSMC exhibited immuno- and cytoskeletal-phenotype, calcium signaling profile and contractile responses similar to bona fide SMC. Passaged iSMC could be expanded to a scale sufficient for large scale tissue replacement. PPC and reprogramed iSMC so derived may offer future opportunities to investigate molecular, structure/function and cell-based replacement therapy approaches to diverse cardiovascular, respiratory, gastrointestinal, and genitourinary diseases that have as their basis smooth muscle cell functional aberrancy or numerical loss. Stem Cells 2016;34:1354-1368. PMID- 26840834 TI - Metabolic Syndrome Components Are Associated with Intervertebral Disc Degeneration: The Wakayama Spine Study. AB - OBJECTIVE: The objective of the present study was to examine the associations between metabolic syndrome (MS) components, such as overweight (OW), hypertension (HT), dyslipidemia (DL), and impaired glucose tolerance (IGT), and intervertebral disc degeneration (DD). DESIGN: The present study included 928 participants (308 men, 620 women) of the 1,011 participants in the Wakayama Spine Study. DD on magnetic resonance imaging was classified according to the Pfirrmann system. OW, HT, DL, and IGT were assessed using the criteria of the Examination Committee of Criteria for MS in Japan. RESULTS: Multivariable logistic regression analysis revealed that OW was significantly associated with cervical, thoracic, and lumbar DD (cervical: odds ratio [OR], 1.28; 95% confidence interval [CI], 0.92-1.78; thoracic: OR, 1.75; 95% CI, 1.24-2.51; lumbar: OR, 1.87; 95% CI, 1.06-3.48). HT and IGT were significantly associated with thoracic DD (HT: OR, 1.54; 95% CI, 1.09-2.18; IGT: OR, 1.65; 95% CI, 1.12-2.48). Furthermore, subjects with 1 or more MS components had a higher OR for thoracic DD compared with those without MS components (vs. no component; 1 component: OR, 1.58; 95% CI, 1.03-2.42; 2 components: OR, 2.60; 95% CI, 1.62-4.20; >=3 components: OR, 2.62; 95% CI, 1.42 5.00). CONCLUSION: MS components were significantly associated with thoracic DD. Furthermore, accumulation of MS components significantly increased the OR for thoracic DD. These findings support the need for further studies of the effects of metabolic abnormality on DD. PMID- 26840835 TI - A Combined In Vitro Imaging and Multi-Scale Modeling System for Studying the Role of Cell Matrix Interactions in Cutaneous Wound Healing. AB - Many cell types remodel the extracellular matrix of the tissues they inhabit in response to a wide range of environmental stimuli, including mechanical cues. Such is the case in dermal wound healing, where fibroblast migrate into and remodel the provisional fibrin matrix in a complex manner that depends in part on the local mechanical environment and the evolving multi-scale mechanical interactions of the system. In this study, we report on the development of an image-based multi-scale mechanical model that predicts the short-term (24 hours), structural reorganization of a fibrin gel by fibroblasts. These predictive models are based on an in vitro experimental system where clusters of fibroblasts (i.e., explants) were spatially arranged into a triangular geometry onto the surface of fibrin gels that were subjected to either Fixed or Free in-plane mechanical constraints. Experimentally, regional differences in short-term structural remodeling and cell migration were observed for the two gel boundary conditions. A pilot experiment indicated that these small differences in the short-term remodeling of the fibrin gel translate into substantial differences in long-term (4 weeks) remodeling, particularly in terms of collagen production. The multi scale models were able to predict some regional differences in remodeling and qualitatively similar reorganization patterns for the two boundary conditions. However, other aspects of the model, such as the magnitudes and rates of deformation of gel, did not match the experiments. These discrepancies between model and experiment provide fertile ground for challenging model assumptions and devising new experiments to enhance our understanding of how this multi-scale system functions. These efforts will ultimately improve the predictions of the remodeling process, particularly as it relates to dermal wound healing and the reduction of patient scarring. Such models could be used to recommend patient specific mechanical-based treatment dependent on parameters such as wound geometry, location, age, and health. PMID- 26840836 TI - Sequential gas delivery provides precise control of alveolar gas exchange. AB - Of the factors determining blood gases, only alveolar ventilation (VA) is amenable to manipulation. However, current physiology text books neither describe how breath-by-breath VA can be measured, nor how it can be precisely controlled in spontaneously breathing subjects. And such control must be effected independent of minute ventilation (VE) and the pattern of breathing. Control of VA requires the deliberate partition of inhaled gas between the alveoli and the anatomical deadspace. This distribution is accomplished by sequential gas delivery (SGD): each breath consists of a chosen volume of 'fresh' gas followed by previously exhaled gas. Control of VA through SGD is a simple, inexpensive, yet powerful tool with many applications. Here we describe how to implement SGD, how it precisely controls VA, and consequently how it controls arterial blood gases. PMID- 26840838 TI - Making and Remaking Dynamic 3D Structures by Shining Light on Flat Liquid Crystalline Vitrimer Films without a Mold. AB - Making dynamic three-dimensional (3D) structures capable of reversible shape changes or locomotion purely out of dry polymers is very difficult. Meanwhile, no previous dynamic 3D structures can be remade into new configurations while being resilient to mechanical damages and low temperature. Here, we show that light activated transesterification in carbon nanotube dispersed liquid crystalline vitrimers enables flexible design and easy building of dynamic 3D structures out of flat films upon irradiation of light without screws, glues, or molds. Shining light also enables dynamic 3D structures to be quickly modified on demand, restored from distortion, repaired if broken, in situ healed when microcrack appears, assembled for more sophisticated structures, reconfigured, and recycled after use. Furthermore, the fabrication, reconfiguration, actuation, reparation, and assembly as well as healing can be performed even at extremely low temperatures (e.g., -130 degrees C). PMID- 26840837 TI - Blockade of dorsolateral pontine 5HT1A receptors destabilizes the respiratory rhythm in C57BL6/J wild-type mice. AB - The neurotransmitter serotonin (5HT) acting via 5HT1a receptors (5HT1aR) is a potent determinant of respiratory rhythm variability. Here, we address the 5HT1aR dependent control of respiratory rhythm variability in C57BL6/J mice. Using the in situ perfused preparation, we compared the effects of systemic versus focal blockade of 5HT1aRs. Blocking 5HT1aRs in the Kolliker-Fuse nucleus (KFn) increased the occurrence of spontaneous apneas and accounted for the systemic effects of 5HT1aR antagonists. Further, 5HT1aRs of the KFn stabilized the respiratory rhythm's response to arterial chemoreflex perturbations; reducing the recovering time, e.g., the latency to return to the baseline pattern. Together, these results suggest that the KFn regulates both intrinsic and sensory determinants of respiratory rhythm variability. PMID- 26840839 TI - LiNbO3-Type Oxide (Tl(1-x)Sc(x))ScO3: High-Pressure Synthesis, Crystal Structure, and Electronic Properties. AB - We investigate the synthesis of a thallium scandate, TlScO3, under high-pressure (6-7.7 GPa) and high-temperature (1373-1773 K) conditions. At 6 GPa, a LiNbO3 type phase appears in a narrow temperature range and in mixtures with other phases. At 7.7 GPa and 1673 K, a new LiNbO3-type oxide is found with a composition of (Tl(1-x)Sc(x))ScO3 and x ~ 0.26 as determined by structural analysis from X-ray powder diffraction data. It crystallizes in space group R3c (No. 161) with lattice parameters of a = 5.50283(7) A and c = 14.4606(2) A. It is stable at least up to 800 K at ambient pressure. The point-charge model gives an electric polarization of 60 MUC/cm(2). First-principles calculations show that centrosymmetric ilmenite-type and polar LiNbO3-type structures of stoichiometric TlScO3 have almost the same lowest energy, and the next stable structure is a GdFeO3-type perovskite structure. PMID- 26840840 TI - A New Fluidized Bed Bioreactor Based on Diversion-Type Microcapsule Suspension for Bioartificial Liver Systems. AB - A fluidized bed bioreactor containing encapsulated hepatocytes may be a valuable alternative to a hollow fiber bioreactor for achieving the improved mass transfer and scale-up potential necessary for clinical use. However, a conventional fluidized bed bioreactor (FBB) operating under high perfusion velocity is incapable of providing the desired performance due to the resulting damage to cell-containing microcapsules and large void volume. In this study, we developed a novel diversion-type microcapsule-suspension fluidized bed bioreactor (DMFBB). The void volume in the bioreactor and stability of alginate/chitosan microcapsules were investigated under different flow rates. Cell viability, synthesis and metabolism functions, and expression of metabolizing enzymes at transcriptional levels in an encapsulated hepatocyte line (C3A cells) were determined. The void volume was significantly less in the novel bioreactor than in the conventional FBB. In addition, the microcapsules were less damaged in the DMFBB during the fluidization process as reflected by the results for microcapsule retention rates, swelling, and breakage. Encapsulated C3A cells exhibited greater viability and CYP1A2 and CYP3A4 activity in the DMFBB than in the FBB, although the increases in albumin and urea synthesis were less prominent. The transcription levels of several CYP450-related genes and an albumin-related gene were dramatically greater in cells in the DMFBB than in those in the FBB. Taken together, our results suggest that the DMFBB is a promising alternative for the design of a bioartificial liver system based on a fluidized bed bioreactor with encapsulated hepatocytes for treating patients with acute hepatic failure or other severe liver diseases. PMID- 26840843 TI - The First Step Is Recognizing, Acknowledging, and Respecting the Inequity, Disrespect, and Disregard Our African American Patients Have Experienced. PMID- 26840844 TI - Hospice and Palliative Care for African Americans: Overcoming Disparities. PMID- 26840841 TI - Loop-Mediated Isothermal Amplification of the sefA Gene for Rapid Detection of Salmonella Enteritidis and Salmonella Gallinarum in Chickens. AB - Salmonella spp. pose a threat to both human and animal health, with more than 2600 serovars having been reported to date. Salmonella serovars are usually identified by slide agglutination tests, which are labor intensive and time consuming. In an attempt to develop a more rapid screening method for the major poultry Salmonella serovars, we developed a loop-mediated isothermal amplification (LAMP) assay, which directly detected the sefA gene, a fimbrial operon gene existing in several specific serovars of Salmonella enterica including the major poultry serovars, namely Salmonella enterica serovar Enteritidis (Salmonella Enteritidis) and Salmonella enterica serovar Gallinarum (Salmonella Gallinarum). With the 177 bacterial strains we tested, positive reactions were only observed with 85 strains of serovar Salmonella Enteritidis and Salmonella Gallinarum. The detection limit of the LAMP assay was 4 CFU/reaction with genomic DNAs of Salmonella Enteritidis (ATCC 13076) from pure culture and 400 CFU/ reaction with DNA extracted from spiked chicken feces. The LAMP assay was more sensitive than conventional culture, especially without enrichment, in detecting Salmonella Enteritidis (CMCC 50041) in the spiked fecal samples. The results show the sefA LAMP method is a rapid, sensitive, specific, and practical method for directly detection of Salmonella Enteritidis and Salmonella Gallinarum in chickens. The sefA LAMP assay can potentially serve as new on-site diagnostics in the poultry industry. PMID- 26840845 TI - Their Bodies, Our Conduct: How Society and Medicine Produce Persons Standing in Need of End-of-Life Care. PMID- 26840846 TI - Undying Hope. PMID- 26840847 TI - Racially Associated Disparities in Hospice and Palliative Care Access: Acknowledging the Facts While Addressing the Opportunities to Improve. PMID- 26840848 TI - Racial Differences in Outcomes of an Advance Care Planning Intervention for Dialysis Patients and Their Surrogates. AB - BACKGROUND: African Americans' beliefs about end-of-life care may differ from those of whites, but racial differences in advance care planning (ACP) outcomes are unknown. OBJECTIVE: The aim of this study was to compare the efficacy of an ACP intervention on preparation for end-of-life decision making and post bereavement outcomes for African Americans and whites on dialysis. METHOD: A secondary analysis of data from a randomized trial comparing an ACP intervention (Sharing Patient's Illness Representations to Increase Trust [SPIRIT]) with usual care was conducted. There were 420 participants, 210 patient-surrogate dyads (67.4% African Americans), recruited from 20 dialysis centers in North Carolina. The outcomes of preparation for end-of-life decision making included dyad congruence on goals of care, surrogate decision-making confidence, a composite of the two, and patient decisional conflict assessed at 2, 6, and 12 months post intervention. Surrogate bereavement outcomes included anxiety, depression, and post-traumatic distress symptoms assessed at 2 weeks, and at 3 and 6 months after the patient's death. RESULTS: SPIRIT was superior to usual care in improving dyad congruence (odds ration [OR] = 2.31, p = 0.018), surrogate decision-making confidence (beta = 0.18, p = 0.021), and the composite (OR = 2.19, p = 0.028) 2 months post-intervention, but only for African Americans. SPIRIT reduced patient decisional conflict at 6 months for whites and at 12 months for African Americans. Finally, SPIRIT was superior to usual care in reducing surrogates' bereavement depressive symptoms for African Americans but not for whites (beta = 3.49, p = 0.003). CONCLUSION: SPIRIT was effective in improving preparation for end-of-life decision-making and post-bereavement outcomes in African Americans. PMID- 26840849 TI - The Impact of Faith Beliefs on Perceptions of End-of-Life Care and Decision Making among African American Church Members. AB - BACKGROUND: African Americans underuse palliative care and hospice services because of a combination of factors including faith beliefs. As the spiritual family for many African Americans, the church presents an opportunity to improve communication about palliative care and hospice and end-of-life (EOL) decision making. OBJECTIVES: We conducted a focus group study to understand the cultural and spiritual perspectives that influence decisions about palliative care and hospice among African American church members who visit and support persons with life-limiting illnesses. Our specific aims were to elicit their perceptions, beliefs, and attitudes about: (1) the relation between faith beliefs and EOL care; (2) emotional and family influences on EOL decision making; (3) palliative care and hospice resources; and (4) opportunities to improve communication among lay persons and health professionals and within families. DESIGN: Seven focus groups using purposeful sampling. SETTINGS/SUBJECTS: We partnered with two African American churches. Of 51 persons, 27 were deacons or deaconesses, 17 were members of health or bereavement ministries, and 7 were other members of the congregations. RESULTS: We found that faith beliefs of African Americans can support discussions about palliative care and hospice. Participants perceived that many of their congregants harbor beliefs, perceptions, and feelings about death and dying that were often not communicated to family members or to health providers. CONCLUSIONS: Among African Americans, faith beliefs, emotional issues, family dynamics, and insufficient knowledge of palliative care and hospice are intertwined and influence decision making about palliative care and hospice. Our findings confirm the influence of faith beliefs of African Americans on decisions about palliative care and hospice and demonstrate the opportunity to improve communication about palliative care and hospice and EOL through collaborations with the African American church. PMID- 26840850 TI - Racial and Ethnic Differences in Advance Directive Possession: Role of Demographic Factors, Religious Affiliation, and Personal Health Values in a National Survey of Older Adults. AB - BACKGROUND: Black and Hispanic older Americans are less likely than white older Americans to possess advance directives. Understanding the reasons for this racial and ethnic difference is necessary to identify targets for future interventions to improve advance care planning in these populations. METHODS: The aim of the study was to evaluate whether racial and ethnic differences in advance directive possession are explained by other demographic factors, religious characteristics, and personal health values. A general population survey was conducted in a nationally representative sample using a web-enabled survey panel of American adults aged 50 and older (n = 2154). RESULTS: In a sample of older Americans, white participants are significantly more likely to possess advance directives (44.0%) than black older Americans (24.0%, p < 0.001) and Hispanic older Americans (29.0%, p = 0.006). Gender, age, retired or disabled employment status, educational attainment, religious affiliation, Internet access, preferences for physician-centered decision making, and desiring longevity regardless of functional status were independent predictors of advance directive possession. In fully adjusted multivariable models with all predictors included, black older Americans remained significantly less likely than white older Americans to have an advance directive (odds ratio [OR] = 0.42, 95% confidence interval [CI] = 0.24-0.75), whereas the effect of Hispanic ethnicity was no longer statistically significant (OR = 0.65, 95% CI = 0.39-1.1). CONCLUSION: In a nationally representative sample, black race is an independent predictor for advance directive possession. This association remains even after adjustment for other demographic variables, religious characteristics, and personal health values. These findings support targeted efforts to mitigate racial disparities in access to advance care planning. PMID- 26840851 TI - Racial Differences in Processes of Care at End of Life in VA Medical Centers: Planned Secondary Analysis of Data from the BEACON Trial. AB - BACKGROUND: Racial differences exist for a number of health conditions, services, and outcomes, including end-of-life (EOL) care. OBJECTIVE: The aim of the study was to examine differences in processes of care in the last 7 days of life between African American and white inpatients. METHODS: Secondary analysis was conducted of data collected in the Best Practices for End-of-Life Care for Our Nation's Veterans (BEACON) trial (conducted 2005-2011). Subjects were 4891 inpatient decedents in six Veterans Administration Medical Centers. Data were abstracted from decedents' medical records. Multi-variable analyses were conducted to examine the relationship between race and each of 18 EOL processes of care controlling for patient characteristics, study site, year of death, and whether the observation was pre- or post-intervention. RESULTS: The sample consisted of 1690 African American patients (34.6%) and 3201 white patients (65.4%). African Americans were less likely to have: do not resuscitate (DNR) orders (odds ratio [OR]: 0.67; p = 0.004), advance directives (OR: 0.71; p = 0.023), active opioid orders (OR: 0.64, p = 0.0008), opioid medications administered (OR: 0.61, p = 0.004), benzodiazepine orders (OR: 0.68, p < 0.0001), benzodiazepines administered (OR: 0.61, p < 0.0001), antipsychotics administered (OR: 0.73, p = 0.004), and steroids administered (OR: 0.76, p = 0.020). Racial differences were not found for other processes of care, including palliative care consultation, pastoral care, antipsychotic and steroid orders, and location of death. CONCLUSIONS: Racial differences exist in some but not all aspects of EOL care. Further study is needed to understand the extent to which racial differences reflect different patient needs and preferences and whether interventions are needed to reduce disparities in patient/family education or access to quality EOL care. PMID- 26840852 TI - A Pilot Feasibility Intervention to Increase Advance Care Planning among African Americans in the Deep South. AB - BACKGROUND: Despite growing efforts to facilitate advance care planning (ACP) to decrease health disparities in palliative care, low completion rates of advance directives (AD) have been consistently found among African Americans. OBJECTIVE: The objective was to examine the feasibility of a multicomponent ACP intervention program that integrates motivational interviewing, evidence-based ACP facilitation program (Respecting Choices((r))), and health-literacy adjusted AD. This pilot study aims to address the unique barriers to ACP engagement among African Americans in the Deep South. METHODS: The design was a mixed-method randomized controlled trial design. Analysis of covariance (ANCOVA) and thematic content analysis (TCA) were conducted to identify barriers and facilitators for ACP engagement and to assess feasibility, knowledge, and intention to complete an AD. Thirty community-dwelling African Americans (mean age M = 55.43, SD = 6.71, range = 47-73) were recruited from the Deep South and randomly assigned to receive intervention (n = 15) or educational material (n = 15) at a local university medical center. RESULTS: All participants (n = 30) reported high satisfaction (M = 4.81, SD = 0.44, max score = 5) and increased intent to complete an AD at postintervention. A significant increase in knowledge on AD from baseline to postintervention was observed in the intervention group-t(14) = 3.06, p = 0.01, d = 1.67); no significant change was found for control. Lack of information, mistrust of doctors, and avoidance of discussing death were primary barriers to ACP discussions. Facilitators include ACP education, decreased mistrust, and proactive initiation of ongoing ACP discussions. CONCLUSIONS: Feasibility data revealed successful implementation of a brief intervention to increase ACP engagement and willingness to complete an AD among southern African Americans. PMID- 26840854 TI - What are Hospice Providers in the Carolinas Doing to Reach African Americans in Their Service Area? AB - BACKGROUND: Experts and national organizations recommend that hospices work to increase service to African Americans, a group historically underrepresented in hospice. OBJECTIVE: The study objective was to describe strategies among hospices in North and South Carolina to increase service to African Americans and identify hospice characteristics associated with these efforts. METHODS: The study was a cross-sectional survey using investigator-developed scales to measure frequency of community education/outreach, directed marketing, efforts to recruit African American staff, cultural sensitivity training, and goals to increase service to African Americans. We used nonparametric Wilcoxon tests to compare mean scale scores by sample characteristics. RESULTS: Of 118 eligible hospices, 79 (67%) completed the survey. Over 80% were at least somewhat concerned about the low proportion of African Americans they served, and 78.5% had set goals to increase service to African Americans. Most were engaged in community education/outreach, with 92.4% reporting outreach to churches, 76.0% to social services organizations, 40.5% to businesses, 35.4% to civic groups, and over half to health care providers; 48.0% reported directed marketing via newspaper and 40.5% via radio. The vast majority reported efforts to recruit African American staff, most often registered nurses (63.75%). Nearly 90% offered cultural sensitivity training to staff. The frequency of strategies to increase service to African Americans did not vary by hospice characteristics, such as profit status, size, or vertical integration, but was greater among hospices that had set goals to increase service to African Americans. CONCLUSIONS: Many hospices are engaged in efforts to increase service to African Americans. Future research should determine which strategies are most effective. PMID- 26840855 TI - Church-Based Health Promotion Focused on Advance Care Planning and End-of-Life Care at Black Baptist Churches: A Cross-Sectional Survey. AB - BACKGROUND: African Americans with serious illnesses receive substandard palliative care (PC) and end-of-life care (EOLC) with a disproportionate number having worse symptom-related suffering, poorer health-related communication and knowledge of advance care planning (ACP) wishes, and increased utilization of hospitals and intensive care units at EOL. Previous research emphasizes the importance of spirituality and the church in African American communities. We are pioneering an innovative partnership between two Baptist African American churches and an interdisciplinary research team with a goal of developing and implementing a community-based, church-centered ACP program. We hypothesize that a church-based approach-which embraces and celebrates religion and spirituality as a means to discuss ACP and EOLC-can improve the quality of EOLC. OBJECTIVE: The aim of the study was to determine parishioner experiences and beliefs about EOLC and their potential desire for a church-based program that would address ACP and EOLC. METHODS: A cross-sectional survey of parishioners at two large black Baptist churches across four weekend services in December 2014 was conducted using a five-question, Likert-scale survey completed on a note card. RESULTS: There were 930 responses submitted. Approximately 70% of parishioners care, or have cared, for someone with multiple medical problems and/or who is dying, and a vast majority (97%) believed that good EOLC is "important" or "very important." Only 60% of respondents noted having spoken with someone who could make decisions for them if they are unable to speak for themselves and that number decreased to 28% of respondents between the ages of 65 and 80. A majority (93%) would welcome church-provided information about EOLC. CONCLUSIONS: A majority of parishioners care for someone with multiple health problems and believe that good EOLC is important. However, significantly less had designated a surrogate decision maker, particularly in parishioners over the age of 65. Respondents would welcome a church-based program focused on improving EOLC. PMID- 26840853 TI - End-of-Life Decision Making and Communication of Bereaved Family Members of African Americans with Serious Illness. AB - OBJECTIVE: The study objective was to examine factors that influence African American (AA) family members' end-of-life care decision outcomes for a relative who recently died from serious illness. METHODS: A cross-sectional descriptive study design was used. Binary logistic and linear regressions were used to identify factors associated with decision regret and decisional conflict. Forty nine bereaved AA family members of AA decedents with serious illness who died two to six months prior to enrollment were recruited from the palliative care program in a safety net hospital and a metropolitan church in the Midwest. Measurements used were the Decisional Conflict, Decision Regret, Beliefs and Values, and Quality of Communication scales. RESULTS: Family members who reported higher quality of communication with health care providers had lower decisional conflict. Family members of decedents who received comfort-focused care (CFC) had significantly less decision regret than family members of those who received life prolonging treatment (LPT). Family members who reported stronger beliefs and values had higher quality of communication with providers and lower decisional conflict. CONCLUSIONS: This research adds to a small body of literature on correlates of end-of-life decision outcomes among AAs. Although AAs' preference for aggressive end-of-life care is well-documented, we found that receipt of CFC was associated with less decision regret. To reduce decisional conflict and decision regret at the end of life, future studies should identify strategies to improve family member-provider communication, while considering relevant family member and decedent characteristics. PMID- 26840856 TI - Palliative Care Teams as Advocates for Adults with Sickle Cell Disease. AB - Medical advances have improved the overall life expectancy of patients with sickle cell disease (SCD). Unfortunately, the quality of life for patients with SCD remains a struggle. As the goal of palliative care (PC) is to improve quality of life for patients with serious illnesses, many PC teams are now asked to be involved in the care of these patients and may have variable levels of experience with SCD. Caring for patients with SCD is a complex and difficult task that often causes a reflexive "groan" from health care providers, which usually signifies a negative health care provider attitude stemmed from feeling uncomfortable in treating this complex patient population. It is important to be aware of these implicit biases and to overcome these feelings by becoming more familiar with the lives and experiences of those with SCD. This report provides an overview of SCD, context for the complexity of caring for this patient population, and areas for partnering in care. PMID- 26840857 TI - Factors Impacting Advance Care Planning among African Americans: Results of a Systematic Integrated Review. AB - BACKGROUND: African Americans (AA) are more likely to receive worse end-of-life (EOL) care and are less likely to participate in advance care planning (ACP) than white Americans. OBJECTIVE: Our goal was to understand factors impacting ACP among AA and explore their interactions, in order to guide further research and intervention development. METHODS: We systematically identified, using Medline, Embase, and World of Science databases, the quantitative and qualitative ACP literature in which AA were included. We assessed the quality of these studies and evaluated the literature in an iterative and integrative fashion, using themes developed from the qualitative literature to understand and categorize findings from the quantitative literature. RESULTS: Thirty-eight mostly moderate and low quality quantitative studies focused largely on advance directive (AD) completion. Whereas most conclude that AA, when compared with white Americans, prefer more aggressive care, participate less in ACP, and are more likely to informally discuss EOL care than to formally document wishes, study findings were contradictory in a number of domains. Fourteen qualitative studies revealed a number of themes that informed the development of an empirically derived model to explain the relationship of factors impacting ACP for AA along historical and structural axes. CONCLUSIONS: The multiple factors that impact ACP for AA are inter-related and may result in part from historical realities that shape contemporary experience. We know little from the data about how best to improve ACP in AA. That AA appear to prefer informal discussions about ACP to formal documentation of preferences suggests that future research should focus on improving ACP conversations among clinicians, patients, and their families in order to improve the receipt of goal-concordant care at EOL. PMID- 26840858 TI - Palliative Care in the African American Community #204. PMID- 26840859 TI - Oral versus Intravenous Acetaminophen #302. PMID- 26840860 TI - My Dad said, "Man UP". PMID- 26840861 TI - Helping African Americans of Faith Embrace End-of-Life Discussions. PMID- 26840862 TI - Dementia. PMID- 26840863 TI - The Interplay of Factitious Disorder and Palliative Care Encounters: A Case Series. AB - BACKGROUND: Individuals with factitious disorders often suffer emotional pain, which motivates them to assume a "sick role" rather than experience the intensity of emotional distress. Such individuals may experience iatrogenic harm as a consequence of their psychological disorder. Their clinicians may develop strong negative emotions such as disgust and the health care system can accrue increased medical costs from diagnostic dilemmas. If the disorder remains unrecognized, the resulting tension can cause interdisciplinary team (IDT) conflicts and impact the effectiveness of care. METHODS: In this article, we describe three cases of factitious behaviors, as either a comorbid illness or an underlying condition, that potentiate untoward health effects among patients seen by a palliative care team. We use these examples to illustrate common features of factious disorders, identify clinical pitfalls when caring for such patients, and offer care strategies for palliative care providers who may encounter such patients with increasing prevalence considering the larger national push to involve palliative care teams earlier in disease trajectories. PMID- 26840865 TI - Long-Range Proton Conduction across Free-Standing Serum Albumin Mats. AB - Free-standing serum-albumin mats can transport protons over millimetre length scales. The results of photoinduced proton transfer and voltage-driven proton conductivity measurements, together with temperature-dependent and isotope-effect studies, suggest that oxo-amino-acids of the protein serum albumin play a major role in the translocation of protons via an "over-the-barrier" hopping mechanism. The use of proton-conducting protein mats opens new possibilities for bioelectronic interfaces. PMID- 26840866 TI - Undergoing Diagnostic Evaluation for Possible Cancer Affects the Health-Related Quality of Life in Patients Presenting with Non-Specific Symptoms. AB - AIM: Undergoing diagnostic evaluation for possible cancer can affect health related quality of life (HRQoL). The aims of this study were to examine the HRQoL in patients undergoing a diagnostic evaluation for possible cancer due to non specific symptoms and further to investigate the impact of socio-demographic and medical factors associated with HRQoL at the time of diagnosis. METHODS: This was a prospective, multicenter survey study that included patients who were referred for a diagnostic evaluation due to non-specific cancer symptoms. Participants completed the EORTC-QLQ-C30 quality of life scale before and after completing the diagnostic evaluation. The baseline and follow-up EORTC-QLQ-C30 scores were compared with reference populations. The impact of socio-demographic and medical factors on HRQoL at follow-up was explored by bootstrapped multivariate linear regression. RESULTS: A total of 838 patients participated in the study; 680 (81%) also completed follow-up. Twenty-two percent of the patients received a cancer diagnosis at the end of follow-up. Patients presented initially with a high burden of symptoms, less role and emotional functioning and a lower global health/QoL. Most domains improved after diagnosis and no clinically important difference between baseline and follow-up scores was found. Patients reported effects on HRQoL both at baseline and at follow-up compared with the Danish reference population and had similar scores as a cancer reference population. Co morbidity, being unemployed and receiving a cancer diagnosis had the greatest effect on HRQoL around the time of diagnosis. CONCLUSIONS: Patients with non specific symptoms reported an affected HRQoL while undergoing a diagnostic evaluation for possible cancer. Morbidity, being unemployed and receiving a cancer diagnosis had the greatest effect on HRQoL around the time of diagnosis. PMID- 26840868 TI - Status Epilepticus Diagnosis, Management and Outcome: An Update. PMID- 26840867 TI - Identification of Eight Different Isoforms of the Glucocorticoid Receptor in Guinea Pig Placenta: Relationship to Preterm Delivery, Sex and Betamethasone Exposure. AB - The placental glucocorticoid receptor (GR) is central to glucocorticoid signalling and for mediating steroid effects on pathways associated with fetal growth and lung maturation but the GR has not been examined in the guinea pig placenta even though this animal is regularly used as a model of preterm birth and excess glucocorticoid exposure. Guinea pig dams received subcutaneous injections of either vehicle or betamethasone at 24 and 12 hours prior to preterm or term caesarean-section delivery. At delivery pup and organ weights were recorded. Placentae were dissected, weighed and analysed using Western blot to examine GR isoform expression in nuclear and cytoplasmic extracts. A comparative examination of the guinea pig GR gene identified it is capable of producing seven of the eight translational GR isoforms which include GRalpha-A, C1, C2, C3, D1, D2, and D3. GRalpha-B is not produced in the Guinea Pig. Total GR antibody identified 10 specific bands from term (n = 29) and preterm pregnancies (n = 27). Known isoforms included GRgamma, GRalpha A, GRbeta, GRP, GRA and GRalpha D1-3. There were sex and gestational age differences in placental GR isoform expression. Placental GRalpha A was detected in the cytoplasm of all groups but was significantly increased in the cytoplasm and nucleus of preterm males and females exposed to betamethasone and untreated term males (KW-ANOVA, P = 0.0001, P = 0.001). Cytoplasmic expression of GRbeta was increased in female preterm placentae and preterm and term male placentae exposed to betamethasone (P = 0.01). Nuclear expression of GRbeta was increased in all placentae exposed to betamethasone (P = 0.0001). GRalpha D2 and GRalpha D3 were increased in male preterm placentae when exposed to betamethasone (P = 0.01, P = 0.02). The current data suggests the sex-specific placental response to maternal betamethasone may be dependent on the expression of a combination of GR isoforms. PMID- 26840869 TI - How to Manage Electrical Status Epilepticus in Sleep. AB - Electrical status epilepticus in sleep is an age-dependent syndrome with the characteristic pattern of continuous spike and waves during non-rapid eye movement sleep. Most children can present developmental deterioration. The demonstration of the EEG pattern has to rely on all night long EEG recordings. A comprehensive neuropsychologic evaluation with periodic reassessment should be performed. For the idiopathic forms of electrical status epilepticus in sleep, clobazam could be considered as the first-line therapy; in the other cases, corticosteroids, in particular intravenous methylprednisolone pulse therapy, remain the most effective and should be considered the therapy of choice. PMID- 26840870 TI - Status Epilepticus: Do Treatment Guidelines Make Sense? AB - Status epilepticus represents an acute, potentially life-threatening emergency with considerable risks of morbidity and mortality, mainly depending on age at onset, underlying etiology, seizure severity, and medical comorbidities. Recent European and North American guidelines on management and treatment of status epilepticus strongly recommend prompt treatment to prevent further complications. At present, following a staged treatment protocol is recommended. Benzodiazepines are the treatment of choice in early status epilepticus, but there are no class I data supporting treatment recommendations on the choice of antiepileptic drugs for established and refractory status epilepticus. This article reviews advantages and potential drawbacks of the available guidelines. PMID- 26840871 TI - Monotherapy or Polytherapy for First-Line Treatment of SE? AB - Status epilepticus (SE) is one of the most frequent neurologic emergencies, and a rapid and effective treatment is warranted. Current guidelines recommend a stepwise approach using a sequence of different antiepileptic drugs with benzodiazepines (BZD) being the first treatment proposed. To provide the more effective treatment as soon as possible, some authors have suggested using a combined polytherapy as first-line treatment. Strong evidence supports the use of benzodiazepines, mostly lorazepam and midazolam as initial monotherapy treatment for SE. Insufficient data are available to support the use of nonsedating antiepileptic drugs as phenytoin, valproic acid, or levetiracetam without a previous benzodiazepine administration. Studies assessing the role of a combined initial therapy are rare, if not missing. Moreover, owing the wide range of SE etiologies, a "one fits all" initial polytherapy seems difficult to achieve. After reviewing the available evidence, guidelines, and current practices regarding monotherapy and polytherapy as first-line treatment in SE in adults, the authors propose a rational algorithm for early antiseizure treatment in SE. PMID- 26840872 TI - Are Newer AEDs Better Than the Classic Ones in the Treatment of Status Epilepticus? AB - Several newer antiepileptic drugs have been increasingly used in patients with status epilepticus, especially levetiracetam and lacosamide, because of their intravenous availability. They may offer advantages in terms of tolerability; however, to date, no clear evidence suggests any advantage regarding efficacy after the use of newer antiepileptic drugs in this specific clinical setting. However, there has been a considerable revival of interest regarding some classic compounds, such as midazolam (MDZ), valproate (VPA), ketamine, or ketogenic diet. Awaiting comparative studies, which in part are ongoing, it seems reasonable, for the first choice, to rely on those agents that are best known and less expensive. PMID- 26840873 TI - Should Barbiturates be Used in Refractory Status Epilepticus? AB - Status epilepticus (SE) is a frequent neurologic emergency, one third of patients do not respond to treatment with benzodiazepines followed by a second antiepileptic drug. While initial treatment of complex partial SE is accordant to that of generalized convulsive SE, further management of refractory SE depends on the risk for acute complications and long-term clinical consequences. These risks are low in complex partial SE; therefore, in this clinical form anesthetics commonly are not used. Generalized convulsive SE-even in its early course-is a potentially life-threatening condition; therefore, prompt use of anesthetics is urgently required. Drugs of choice are barbiturates, midazolam, and propofol, all of which exhibit specific advantages and disadvantages. Up to now, data from clinical studies do not allow to prefer or to discard one of these anesthetics, therefore also barbiturates still should be used in refractory SE. A widely accepted in-house protocol for the management of initial and refractory SE is highly recommended. PMID- 26840874 TI - Are We Prepared to Detect Subtle and Nonconvulsive Status Epilepticus in Critically Ill Patients? AB - Continuous electroencephalography uncovers a clinically underappreciated burden of subtle and nonconvulsive status epilepticus in critically ill patients. Prolonged recordings over days are labor intensive and patient or medical equipment related electrographic artifacts are challenging, calling for a targeted use of electroencephalography in patients with defined seizure risk profiles. This review compiles current data of the impact of continuous electroencephalography on the detection of subtle and nonconvulsive status epilepticus in different clinical scenarios and its contribution to treatment and monitoring in intensive care units. Current recommendations on the use of continuous electroencephalography in the critically ill are outlined. PMID- 26840875 TI - Is Favorable Outcome Possible After Prolonged Refractory Status Epilepticus? AB - When status epilepticus (SE) remains refractory to appropriate therapy, it is associated with high mortality and with substantial morbidity in survivors. Many outcome predictors such as age, seizure type, level of consciousness before treatment, and mostly, etiology, are well-established. A longer duration of SE is often associated with worse outcome, but duration may lose its prognostic value after several hours. Several terms and definitions have been used to describe prolonged, refractory SE, including "malignant SE," "prolonged" SE, and more recently, "super refractory" SE, defined as "SE that has continued or recurred despite 24 hours of general anesthesia (or coma-inducing anticonvulsants)." There are few data available regarding the outcome of prolonged refractory SE, and even fewer for SE remaining refractory to anesthetic drugs. This article reviews reports of outcome after prolonged, refractory, and "super refractory" SE. Most information detailing the clinical outcome of patients surviving these severe illnesses, in which seizures can persist for days or weeks (and especially those concerning "super-refractory" SE) come from case reports and retrospective cohort studies. In many series, prolonged, refractory SE has a mortality of 30% to 50%, and several studies indicate that most survivors have a substantial decline in functional status. Nevertheless, several reports demonstrate that good functional outcome is possible even after several days of SE and coma induction. Treatment of refractory SE should not be withdrawn from younger patients without structural brain damage at presentation solely because of the duration of SE. PMID- 26840877 TI - Spatially Non-uniform Trap State Densities in Solution-Processed Hybrid Perovskite Thin Films. AB - The facile solution-processability of methylammonium lead halide (CH3NH3PbI3) perovskites has catalyzed the development of inexpensive, hybrid perovskite-based optoelectronics. It is apparent, though, that solution-processed CH3NH3PbI3 films possess local emission heterogeneities, stemming from electronic disorder in the material. Herein we investigate the spatially resolved emission properties of CH3NH3PbI3 thin films through detailed emission intensity versus excitation intensity measurements. These studies enable us to establish the existence of nonuniform trap density variations wherein regions of CH3NH3PbI3 films exhibit effective free carrier recombination while others exhibit emission dynamics strongly influenced by the presence of trap states. Such trap density variations lead to spatially varying emission quantum yields and correspondingly impact the performance of both methylammonium lead halide perovskite solar cells and other hybrid perovskite-based devices. Of additional note is that the observed spatial extent of the optical disorder extends over length scales greater than that of underlying crystalline domains, suggesting the existence of other factors, beyond grain boundary-related nonradiative recombination channels, which lead to significant intrafilm optical heterogeneities. PMID- 26840876 TI - Prognostic Values of Motor Evoked Potentials in Insular, Precental, or Postcentral Resections. AB - PURPOSE: To determine the predictive values of motor evoked potentials (MEPs) on the muscle strength of patients undergoing insular and/or around precentral or postcentral neurosurgeries. METHODS: Neurosurgeries were performed in 104 patients with continuous MEPs elicited with direct cortical and/or transcranial stimulation (DCS, TES; alarm criterion: reproducible 50% decrease in the MEP amplitudes). Muscle strength was evaluated with the British Medical Research Council Scale, before and postoperatively (1-3 days, 3 months). RESULTS: Permanent decreases in DCS-MEPs identified all new upper limbs deficits (sensitivity: 100%; TES-MEPs: 82.3% upper, 78.6% lower limbs). All MEP decreases predicted deficits (positive predictive value: 100%). None of the stable limbs were associated with MEP decrease (specificity: 100%). All unchanged DCS-MEPs predicted unchanged strength (negative predictive values: 100%; TES-MEPs: 95.3% upper, 95.5% lower limbs). The risks of paresis at 3 months were of 0% with none or MEP deterioration <50%; 1.1% (1/91 patients) with MEP deterioration (50%-90%); 7.7% (7/91 patients) with MEP loss. Deficits at 3 months were due to ischemia detected intraoperatively (4.8%, 5/104 patients) or consequent to postoperative hemorrhage (5.8%, 6/104 patients) or to disease progression (2.9%, 3/104 patients). CONCLUSIONS: The primary motor cortex and corticospinal pathway can reliably be monitored to protect motor strength during insular, precentral, and postcentral resections under general anesthesia. Nevertheless, MEPs did not prevent subcortical ischemias that might be reduced with continuous subcortical mapping. For the preservation of complex motor functions, for example, bimanual coordination, not evaluated here, insular surgeries can be performed with awake surgeries for which decision to undergo remains to the patient, aware of possible shorter survival. PMID- 26840878 TI - High Trans Kinetic Selectivity in Ruthenium-Based Olefin Cross-Metathesis through Stereoretention. AB - The first kinetically controlled, highly trans-selective (>98%) olefin cross metathesis reaction is demonstrated using Ru-based catalysts. Reactions with either trans or cis olefins afford products with highly trans or cis stereochemistry, respectively. This E-selective olefin cross-metathesis is shown to occur between two trans olefins and between a trans olefin and a terminal olefin. Additionally, new stereoretentive catalysts have been synthesized for improved reactivity. PMID- 26840879 TI - Abnormal findings in peers during skills learning. AB - BACKGROUND: Peer physical examination (PPE), where students examine each other, is common in contemporary clinical skills learning. A range of benefits and risks have been explored in the literature. One persistent concern has been the identification and management of abnormal physical findings. Two previous studies have attempted to quantify the risk, one through the discussion of two exemplar cases and the other with a retrospective student survey. METHODS: Here, we report the first prospective study of the number and type of abnormalities encountered as part of early clinical skills learning in a medical programme. We have a formal written consent process for PPE, which includes the management of abnormal findings through the completion of an event form. Our data come from cohorts undertaking years 2 and 3 of the programme between 2003 and 2014. One persistent concern (of PPE) has been the identification and management of abnormal physical findings RESULTS: Nineteen event forms were completed over this period. The incidence rates per year ranged from 0.23 to 1.05 per cent. Abnormal findings included raised blood pressure, heart murmur, abnormal bedside test values, and eye and skin conditions. DISCUSSION: The low event rate, along with a feasible process for dealing with this issue, goes some way to reassuring those with concerns. We acknowledge that some abnormalities may have been missed, and that some data may have been lost as a result of incorrect process; however, even the highest annual rate is low in absolute terms. We recommend a formal process for managing abnormalities. Ideally this would be part of an overall PPE written policy, communicated to students, enacted by tutors and approved by the local ethics committee. PMID- 26840880 TI - Reply: The Optimal Dose of Hypofractionated Radiotherapy in Diffuse Intrinsic Pontine Glioma (DIPG). PMID- 26840881 TI - Selective Growth of Noble Gases at Metal/Oxide Interface. AB - The locations and roles of noble gases at an oxide/metal interface in oxide dispersed metal are theoretically and experimentally investigated. Oxide dispersed metal consisting of FCC Fe and Y2Hf2O7 (Y2Ti2O7) is synthesized by mechanical alloying under a saturated Ar gas environment. Transmission electron microscopy and density functional theory observes the strain field at the interface of FCC Fe {111} and Y2Hf2O7 {111} whose physical origin emerges from surface reconstruction due to charge transfer. Noble gases are experimentally observed at the oxide (Y2Ti2O7) site and calculations reveal that the noble gases segregate the interface and grow toward the oxide site. In general, the interface is defined as the trapping site for noble gases; however, transmission electron microscopy and density functional theory found evidence which shows that noble gases grow toward the oxide, contrary to the generally held idea that the interface is the final trapping site for noble gases. Furthermore, calculations show that the inclusion of He/Ar hardens the oxide, suggesting that material fractures could begin from the noble gas bubble within the oxides. Thus, experimental and theoretical results demonstrate that noble gases grow from the interface toward the oxide and that oxides behave as a trapping site for noble gases. PMID- 26840882 TI - A porous carbon derived from amino-functionalized material of Institut Lavoisier as a solid-phase microextraction fiber coating for the extraction of phthalate esters from tea. AB - In this work, a porous carbon derived from amino-functionalized material of Institut Lavoisier (C-NH2 -MIL-125) was prepared and coated onto a stainless steel wire through sol-gel technique. The coated fiber was used for the solid phase microextraction of trace levels of phthalate esters (diallyl phthalate, di iso-butyl ortho-phthalate, di-n-butyl ortho-phthalate, benzyl-n-butyl ortho phthalate, and bis(2-ethylhexy) ortho-phthalate) from tea beverage samples before gas chromatography with mass spectrometric analysis. Several experimental parameters that could influence the extraction efficiency such as extraction time, extraction temperature, sample pH, sample salinity, stirring rate, desorption temperature and desorption time, were investigated. Under the optimal conditions, the linearity existed in the range of 0.05-30.00 MUg/L for green jasmine tea beverage samples, and 0.10-30.00 MUg/L for honey jasmine tea beverage samples, with the correlation coefficients (r) ranging from 0.9939 to 0.9981. The limits of detection of the analytes for the method were 2.0-3.0 ng/L for green jasmine tea beverage sample, and 4.0-5.0 ng/L for honey jasmine tea beverage sample, depending on the compounds. The recoveries of the analytes for the spiked samples were in the range of 82.0-106.0%, and the precision, expressed as the relative standard deviations, was less than 11.1%. PMID- 26840883 TI - Relationship between nurses' practice environments and nursing outcomes in Turkey. AB - AIM: This study aimed to understand nursing practice environment characteristics in Istanbul-area hospitals in Turkey, the relationship between these characteristics, nurse burnout levels and nurses' intentions to leave work. BACKGROUND: A well-known relationship exists in many countries between nursing practice environments and nurse burnout and intention to leave work. However, little is known about the relationship between practice environment characteristics and nursing outcomes in Turkey. METHODS: This cross-sectional study was conducted among 2592 nurses in 20 Ministry of Health and 29 private hospitals in Istanbul, Turkey. A demographic questionnaire, Practice Environment Scale of the Nursing Work Index and Maslach Burnout Inventory were used for data collection. RESULTS: Almost half of nurses suffered from high-level burnout related to emotional exhaustion and personal accomplishment, and one-third reported depersonalization and the intent to leave their jobs within a year. A poor nursing practice environment was the leading factor, increasing nurses' burnout levels in all subdimensions. Burnout related to emotional exhaustion, personal accomplishment and poor practice environment increased intention to leave. Permanent positions decreased intention. DISCUSSION: There was a relationship between poor practice environments and nursing outcomes in Turkey. LIMITATIONS: The use of a survey data collection method is a potential study limitation. Quantitative and qualitative methods could be combined to obtain more detailed objective data about nursing practice environments. CONCLUSION: Poor practice environments, high-level burnout and intention to leave work are significant problems in Istanbul, Turkey. Favourable practice environments and job security should be provided to improve nursing outcomes. IMPLICATIONS FOR NURSING POLICY: Policymakers and nurse managers should be aware of any negative issues regarding nursing practice environments and job security to improve nursing outcomes. PMID- 26840884 TI - Fast patterning of oriented organic microstripes for field-effect ammonia gas sensors. AB - A series of organic field-effect transistors (OFETs) with patterned ultra-thin films for NH3 detection are achieved via fast dip-coating. The morphology and packing structure of the ultra-thin films are greatly dependent on the surface energy of the substrates, geometry features of the patterned electrodes and evaporation atmosphere during the dip-coating process, which in turn results in a significant difference in the NH3 sensing properties. Based on the newly proposed mechanism, low-trap dielectric-semiconductor interfaces, a stripe-like morphology and an ultrathin film (as low as 2 nm) enable the OFET-based sensors to exhibit unprecedented sensitivity (~160) with a short response/recovery time. The efficient (2 mm s(-1)), reliable, and scalable patterning strategy opens a new route for solution-processed OFET-based gas sensors. PMID- 26840886 TI - Congenital rubella syndrome with death from interstitial pneumonia. AB - There was a rubella epidemic in Japan in 2012-2013, which led to an increased number infants being born with congenital rubella syndrome (CRS). Symptoms of CRS are varied and include cataracts, congenital heart disease, and hearing impairment, but case reports of CRS complicated by interstitial pneumonia are rare. We report the case of a patient with CRS who died of respiratory failure caused by interstitial pneumonia. Thrombocytopenia had been present for approximately 1 month after birth, and the patient presented with sudden lung hemorrhage at 64 days old. Thereafter, respiratory condition deteriorated, and the patient died at 107 days old. Given that infants with CRS who have thrombocytopenia and interstitial pneumonia have a high risk of death, they should be monitored carefully for potential complications. PMID- 26840885 TI - Donor positive blood culture is associated with delayed graft function in kidney transplant recipients: a propensity score analysis of the UNOS database. AB - BACKGROUND: The effect of blood culture positive donor (BCPD) on delayed graft function (DGF) in kidney transplant recipients has not been well established. METHODS: We retrieved data from the United Network for Organ Sharing (UNOS) registry on all adults who underwent primary, single organ deceased-donor kidney transplantation in US between 2008 and 2013. Patients were classified in two cohorts: the BCPD cohort and the non-BCPD cohort. We used propensity scores for 1:1 matching of BCPD and non-BCPD cohorts. DGF, graft and patient survival at one yr were compared between cohorts using multivariable logistic and Cox regression models. DGF was defined as requiring dialysis within the first week post transplant. RESULTS: There were 4126 (8.1%) recipients of BCPD during the study period. DGF was associated with BCPD (aOR; 1.15, 95% CI 1.07-1.24). This association was maintained in the propensity-score matched analysis (p < 0.01). No association was found between BCPD and graft survival (aHR; 1.01, 95% CI, 0.92 1.09) or patient survival (aHR; 0.92, 95% CI, 0.82-1.04). CONCLUSION: Blood culture positive donor was associated with DGF but did not impact graft or patient survival in deceased-donor kidney transplants. This suggests a transient negative effect of BCPD that does not appear to translate into a more persistent deleterious outcome. PMID- 26840887 TI - Ingestion of bioactive collagen hydrolysates enhance facial skin moisture and elasticity and reduce facial ageing signs in a randomised double-blind placebo controlled clinical study. AB - BACKGROUND: Several human studies have demonstrated occurrence of two major collagen peptides, prolyl-hydroxyproline (Pro-Hyp) and hydroxyprolyl-glycine (Hyp Gly), in human peripheral blood. Some in vitro studies have demonstrated that Pro Hyp and Hyp-Gly exert chemotaxis on dermal fibroblasts and enhance cell proliferation. Additionally, Pro-Hyp enhances the production of hyaluronic acid by dermal fibroblasts. These findings suggest that the amounts of Pro-Hyp and Hyp Gly in blood are important factors to show the efficacy of collagen hydrolysates on skin health. RESULTS: We conducted a randomised double-blind placebo controlled clinical trial of ingestion of two types of collagen hydrolysates, which are composed of different amounts of the bioactive dipeptides Pro-Hyp and Hyp-Gly, to investigate their effects on the improvement of skin conditions. Improvement in skin conditions, such as skin moisture, elasticity, wrinkles, and roughness, were compared with a placebo group at baseline, and 4 and 8 weeks after the start of the trial. In addition, the safety of dietary supplementation with these peptides was evaluated by blood test. Collagen hydrolysate with a higher content of bioactive collagen peptides (H-CP) showed significant and more improvement than the collagen hydrolysate with a lower content of bioactive collagen peptides (L-CP) and the placebo, in facial skin moisture, elasticity (R2), wrinkles and roughness, compared with the placebo group. In addition, there were no adverse events during the trial. CONCLUSION: This study demonstrated that the use of the collagen hydrolysate with a higher content of Pro-Hyp and Hyp-Gly led to more improvement in facial skin conditions, including facial skin moisture, elasticity, wrinkles and roughness. (c) 2016 Society of Chemical Industry. PMID- 26840888 TI - Can we detect Li K X-ray in lithium compounds using energy dispersive spectroscopy? AB - Lithium is the key element for the development of battery and new technology and the development of an analytical technique to spatially and quantitatively resolve this element is of key importance. Detection of Li K in pure metallic lithium is now possible in the Scanning Electron Microscope (SEM) with newly designed Energy Dispersive Spectroscopy (EDS). However, this work is clearly showing, for the first time using EDS, the detection of Li K in several binary lithium compounds (LiH, Li3 N, Li2 S, LiF and LiCl). Experimental Li K X-rays intensity is compared with a specially modified Monte Carlo simulation program showing discrepancies between theoretical and experimental Li K measurements. The effect of chemical bounding on the X-rays emission using density functional theory with the all-electron linearized augmented plane wave is showing that the emission of Li K from the binary compounds studied should be, at least, 12 times lower than in metallic Li. SCANNING 38:571-578, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26840889 TI - Hybrid Amine-Functionalized Graphene Oxide as a Robust Bifunctional Catalyst for Atmospheric Pressure Fixation of Carbon Dioxide using Cyclic Carbonates. AB - An environmentally-benign carbocatalyst based on amine-functionalized graphene oxide (AP-GO) was synthesized and characterized. This catalyst shows superior activity for the chemical fixation of CO2 into cyclic carbonates at the atmospheric pressure. The developed carbocatalyst exhibits superior activity owing to its large surface area with abundant hydrogen bonding donor (HBD) capability and the presence of well-defined amine functional groups. The presence of various HBD and amine functional groups on the graphene oxide (GO) surface yields a synergistic effect for the activation of starting materials. Additionally, this catalyst shows high catalytic activity to synthesize carbonates at 70 degrees C and at 1 MPa CO2 pressure. The developed AP-GO could be easily recovered and used repetitively in up to seven recycle runs with unchanged catalyst activity. PMID- 26840890 TI - Distance and near visual performance in pseudophakic eyes with simulated spherical and astigmatic blur. AB - PURPOSE: Increased depth-of-focus after cataract surgery is dependent on various ocular characteristics, including refractive astigmatism. This work studied the influence of meridional blur produced by astigmatism, and spherical blur, on distance and near visual performance in pseudophakic eyes. METHODS: Visual performance was assessed monocularly in 59 pseudophakes (mean +/- standard deviation, 66.9 +/- 7.53 years) at distance (3.0 m) and near (0.33 m) using high- (HC: 94%) and low-contrast (LC: 10%) visual acuity (VA) charts. Reading performance (maximum reading speed [MRS], threshold print size [TPS] and reading acuity [RA]) was evaluated at near using a reading chart. Four refractive conditions at distance and near were monocularly simulated using the following trial lenses: distance (in-focus: +/- 0.00 DS, with-the-rule [WTR] astigmatism: +2.00 * 180; against-the-rule [ATR] astigmatism: +2.00 * 90; spherical defocus: +1.00 DS) and near (in-focus: +3.00 DS, WTR astigmatism: +2.00 * 180; ATR astigmatism: +2.00 * 90, spherical blur: +/-0.00 DS). RESULTS: Distance high- and low-contrast VA were degraded by spherical and astigmatic blur in comparison to the distance in-focus condition (p < 0.001 for all), with astigmatism in either of the forms being more harmful than spherical blur (p < 0.001 for all). At near, best HC- and LCVA were attained with full near correction (p < 0.001 for all) followed by the ATR and WTR astigmatism. For all conditions, the VA measured was independent of whether the astigmatism was WTR or ATR. However, MRS was higher with +3.00 DS and ATR astigmatism compared to the other conditions. RA and TPS significantly strengthened the weak pattern seen with HCVA at near, with ATR astigmatism allowing significantly better RA and TPS than WTR astigmatism (p < 0.001 for all). CONCLUSIONS: Simple myopic astigmatism improved near visual performance in pseudophakic eyes at the expense of some deterioration in distance performance. ATR astigmatism degraded VA at distance marginally more than WTR astigmatism and provided a marginally better VA at near. However, the benefit at near was more explicit when measured by reading performance, confirming the role of blur orientation on visual performance. PMID- 26840892 TI - Investigation of the effect of traditional Chinese medicine on pain and inflammation in chronic nonbacterial prostatitis in rats. AB - According to traditional Chinese medicine, the symptoms of chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CNP/CPPS) may be treated using a cocktail of herbs that stimulate blood circulation ('activating blood circulation formula'). We investigated the effect of three doses of this formula on a rat model of CNP/CPPS. Male Wistar rats were injected with a saline extract of male sex accessory glands on days 0 and 30 to induce prostatitis and then treated daily by gavage between days 32 and 60. Treatment with low, medium and high doses of activating blood circulation formula resulted in an almost total rescue of paw withdrawal threshold at day 60, and treatment with the highest dose also significantly decreased prostate inflammation (assessed histopathologically). We further observed elevated serum prostaglandin E2 levels in the CNP/CPPS model which decreased upon high-dose treatment, and increased Cox-2 expression in the prostate and spinal cord dorsal horn which was rescued in both tissues in the high-dose group and in the prostate in the medium-dose group. These results shed light on a possible mechanism by which activating blood circulation therapy may alleviate pain in a rat model of CNP/CPPS by downregulating Cox-2 expression in the spinal cord, thereby raising the pain threshold. Further research will be needed to fully characterise the mechanism by which activating blood circulation therapy produces this therapeutic effect. PMID- 26840893 TI - Correction: Body Size Adaptations to Altitudinal Climatic Variation in Neotropical Grasshoppers of the Genus Sphenarium (Orthoptera: Pyrgomorphidae). PMID- 26840891 TI - The Sociospatial Network: Risk and the Role of Place in the Transmission of Infectious Diseases. AB - Control of sexually transmitted infections and blood-borne pathogens is challenging due to their presence in groups exhibiting complex social interactions. In particular, sharing injection drug use equipment and selling sex (prostitution) puts people at high risk. Previous work examining the involvement of risk behaviours in social networks has suggested that social and geographic distance of persons within a group contributes to these pathogens' endemicity. In this study, we examine the role of place in the connectedness of street people, selected by respondent driven sampling, in the transmission of blood-borne and sexually transmitted pathogens. A sample of 600 injection drug users, men who have sex with men, street youth and homeless people were recruited in Winnipeg, Canada from January to December, 2009. The residences of participants and those of their social connections were linked to each other and to locations where they engaged in risk activity. Survey responses identified 101 unique sites where respondents participated in injection drug use or sex transactions. Risk sites and respondents' residences were geocoded, with residence representing the individuals. The sociospatial network and estimations of geographic areas most likely to be frequented were mapped with network graphs and spatially using a Geographic Information System (GIS). The network with the most nodes connected 7.7% of respondents; consideration of the sociospatial network increased this to 49.7%. The mean distance between any two locations in the network was within 3.5 kilometres. Kernel density estimation revealed key activity spaces where the five largest networks overlapped. Here, the combination of spatial and social entities in network analysis defines the overlap of vulnerable populations in risk space, over and above the person to person links. Implications of this work are far reaching, not just for understanding transmission dynamics of sexually transmitted infections by identifying activity "hotspots" and their intersection with each social network, but also for the spread of other diseases (e.g. tuberculosis) and targeting prevention services. PMID- 26840894 TI - Molecular basis of HSF regulation. PMID- 26840895 TI - Exploiting the exploiter: a viral inhibitor stabilizes TAP for cryo-EM. PMID- 26840896 TI - Structure of a DNA enzyme. PMID- 26840897 TI - N6-methyladenosine-encoded epitranscriptomics. AB - N6-methyladenosine (m6A) is the most abundant internal modification in eukaryotic mRNA. Recent discoveries of the locations, functions and mechanisms of m6A have shed light on a new layer of gene regulation at the RNA level, giving rise to the field of m6A epitranscriptomics. In this Perspective, we provide an update on the various effects of mammalian m6A modification, which affects many different stages of the RNA life cycle. PMID- 26840900 TI - Correction: The Synergistic Local Immunosuppressive Effects of Neural Stem Cells Expressing Indoleamine 2,3-Dioxygenase (IDO) in an Experimental Autoimmune Encephalomyelitis (EAE) Animal Model. PMID- 26840899 TI - Current MUAC Cut-Offs to Screen for Acute Malnutrition Need to Be Adapted to Gender and Age: The Example of Cambodia. AB - BACKGROUND: Early identification of children <5 yrs with acute malnutrition is a priority. Acute malnutrition is defined by the World Health Organization as a mid upper-arm circumference (MUAC) <12.5 cm or a weight-for-height Z-score (WHZ) <-2. MUAC is a simple and low-cost indicator to screen for acute malnutrition in communities, but MUAC cut-offs currently recommended by WHO do not identify the majority of children with weight-for-height Z-score (<-2 (moderate malnourished) or r<-3 (severe malnourished). Also, no cut-offs for MUAC are established for children >5 yrs. Therefore, this study aimed at defining gender and age-specific cut-offs to improve sensitivity of MUAC as an indicator of acute malnutrition. METHODS: To establish new age and gender-specific MUAC cut-offs, pooled data was obtained for 14,173 children from 5 surveys in Cambodia (2011-2013). Sensitivity, false positive rates, and areas under receiver-operator characteristic curves (AUC) were calculated using wasting for children <5yrs and thinness for children >=5yrs as gold standards. Among the highest values of AUC, the cut-off with the highest sensitivity and a false positive rate <=33% was selected as the optimal cut-off. RESULTS: Optimal cut-off values increased with age. Boys had higher cut offs than girls, except in the 8-10.9 yrs age range. In children <2yrs, the cut off was lower for stunted children compared to non stunted children. Sensitivity of MUAC to identify WHZ<-2 and <-3 z-scores increased from 24.3% and 8.1% to >80% with the new cut-offs in comparison with the current WHO cut-offs. CONCLUSION: Gender and age specific MUAC cut-offs drastically increased sensitivity to identify children with WHZ-score <-2 z-scores. International reference of MUAC cut-offs by age group and gender should be established to screen for acute malnutrition at the community level. PMID- 26840898 TI - Replication stress: getting back on track. AB - The replication-stress response enables the DNA replication machinery to overcome DNA lesions or intrinsic replication-fork obstacles, and it is essential to ensure faithful transmission of genetic information to daughter cells. Multiple replication stress-response pathways have been identified in recent years, thus raising questions about the specific and possibly redundant functions of these pathways. Here, we review the emerging mechanisms of the replication-stress response in mammalian cells and consider how they may influence the dynamics of the core DNA replication complex. PMID- 26840901 TI - Spectroscopy of Single Dibenzoterrylene Molecules in para-Dichlorobenzene. AB - We study single dibenzoterrylene (DBT) molecules embedded in 1,4-dichlorobenzene (para-dichlorobenzene, pDCB) at 1.2 K. Due to the relatively low melting point of pDCB (53 degrees C), this host-guest system can be easily prepared from the molten phase. Narrow linewidths, stable molecular lines and high saturation count rates of single DBT molecules were observed. For this reason, we consider this host-guest system a promising candidate for the study of interactions of single molecules with other small objects such as waveguides or nanoparticles. PMID- 26840902 TI - A Randomized Trial of Ketorolac vs. Sumatripan vs. Placebo Nasal Spray (KSPN) for Acute Migraine. AB - OBJECTIVE: To compare the efficacy of ketorolac nasal spray (NS) vs. placebo and sumatriptan NS for the acute treatment of migraine. METHODS: This was a randomized, double-blind, placebo and active-comparator, crossover study. Adult migraineurs were randomized to ketorolac NS 31.5 mg, sumatriptan NS 20 mg, or placebo to treat three moderate to severe migraine attacks and switched treatments with each attack. Patients seeking headache care at a headache center or in response to community advertisement were recruited. Adult participants with episodic migraine who experienced >=2 migraine attacks per month were eligible for the Ketorolac vs. Sumatriptan vs. Placebo Nasal Spray migraine study. Participants were randomized to treatment arms by a research pharmacist, in a 1:1:1 ratio using computer-generated lists. The primary outcome was 2-hour pain relief. Secondary outcomes included 2-hour pain freedom and absence of migraine associated symptoms, and 24-hour sustained pain relief and pain freedom. RESULTS: Of the 72 randomized participants, 54 (75%) treated at least one attack and 49 (68%) completed all three treatments, for a total of 152 treated migraine attacks. Both ketorolac NS (72.5%, P < .001) and sumatriptan NS (69.4%, P = .001) were more effective than placebo (38.3%) for 2-hour pain relief and 2-hour pain freedom (ketorolac: 43.1%, P = .004; sumatriptan: 36.7%, P = .046; placebo: 18.4%). Ketorolac NS, but not sumatriptan NS, was more effective than placebo in 2-hour absence of nausea. Both ketorolac NS and sumatriptan NS were more effective than placebo for 24-hour sustained pain relief (ketorolac: 49%, P < .001; sumatriptan: 31%, P = .01, placebo: 20%). Only ketorolac NS was superior to placebo for 24-hour (ketorolac: 35.3%, P = .003; sumatriptan: 22.4%, P = .18, placebo: 12.2%) sustained pain freedom. Nasal burning and dysgeusia were the most common adverse effects for active treatments. CONCLUSIONS: This study supports that ketorolac NS is superior to placebo and that it is non-inferior to sumatriptan NS for the acute abortive treatment of migraine. PMID- 26840903 TI - Allergic Patients with Long-Term Asthma Display Low Levels of Bifidobacterium adolescentis. AB - Accumulated evidence suggests a relationship between specific allergic processes, such as atopic eczema in children, and an aberrant fecal microbiota. However, little is known about the complete microbiota profile of adult individuals suffering from asthma. We determined the fecal microbiota in 21 adult patients suffering allergic asthma (age 39.43 +/- 10.98 years old) and compare it with the fecal microbiota of 22 healthy controls (age 39.29 +/- 9.21 years old) using culture independent techniques. An Ion-Torrent 16S rRNA gene-based amplification and sequencing protocol was used to determine the fecal microbiota profile of the individuals. Sequence microbiota analysis showed that the microbial alpha diversity was not significantly different between healthy and allergic individuals and no clear clustering of the samples was obtained using an unsupervised principal component analysis. However, the analysis of specific bacterial groups allowed us to detect significantly lower levels of bifidobacteria in patients with long-term asthma. Also, in allergic individuals the Bifidobacterium adolescentis species prevailed within the bifidobacterial population. The reduction in the levels on bifidobacteria in patients with long term asthma suggests a new target in allergy research and opens possibilities for the therapeutic modulation of the gut microbiota in this group of patients. PMID- 26840905 TI - Monochrome Multiplexing in Polymerase Chain Reaction by Photobleaching of Fluorogenic Hydrolysis Probes. AB - Multiplexing in polymerase chain reaction (PCR) is a technique widely used to save cost and sample material and to increase sensitivity compared to distributing a sample to several singleplex reactions. One of the most common methods to detect the different amplification products is the use of fluorogenic probes that emit at different wavelengths (colors). To reduce the number of detection channels, several methods for monochrome multiplexing have been suggested. However, they pose restrictions to the amplifiable target length, the sequence, or the melting temperature. To circumvent these limitations, we suggest a novel approach that uses different fluorophores with the same emission maximum. Discrimination is achieved by their different fluorescence stability during photobleaching. Atto488 (emitting at the same wavelength as 6-carboxyfluorescein, FAM) and Atto467N (emitting at the same wavelength as cyanine 5, Cy5) were found to bleach significantly less than FAM and Cy5; i.e., the final fluorescence of Atto dyes was more than tripled compared to FAM and Cy5. We successfully applied this method by performing a 4-plex PCR targeting antibiotic resistance genes in S. aureus using only 2 color channels. Confidence of discrimination between the targets was >99.9% at high copy initial copy numbers of 100 000 copies. Cases where both targets were present could be discriminated with equal confidence for Cy5 channel and reduced levels of confidence (>68%) for FAM channel. Moreover, a 2-plex digital PCR reaction in 1 color channel was shown. In the future, the degree of multiplexing may be increased by adding fluorogenic probe pairs with other emission wavelengths. The method may also be applied to other probe and assay formats, such as Forster resonance energy transfer (FRET) probes and immunoassays. PMID- 26840904 TI - Prediabetes Phenotype Influences Improvements in Glucose Homeostasis with Resistance Training. AB - PURPOSE: To determine if prediabetes phenotype influences improvements in glucose homeostasis with resistance training (RT). METHODS: Older, overweight individuals with prediabetes (n = 159; aged 60+/-5 yrs; BMI 33+/-4 kg/m2) completed a supervised RT program twice per week for 12 weeks. Body weight and composition, strength, fasting plasma glucose, 2-hr oral glucose tolerance, and Matsuda Defronza estimated insulin sensitivity index (ISI) were assessed before and after the intervention. Participants were categorized according to their baseline prediabetes phenotype as impaired fasting glucose only (IFG) (n = 73), impaired glucose tolerance only (IGT) (n = 21), or combined IFG and IGT (IFG/IGT) (n = 65). RESULTS: Chest press and leg press strength increased 27% and 18%, respectively, following the 12-week RT program (both p<0.05). Waist circumference (-1.0%; pre 109.3+/-10.3 cm, post 108.2+/-10.6 cm) and body fat (-0.6%; pre 43.7+/-6.8%, post 43.1+/-6.8%) declined, and lean body mass (+1.3%; pre 52.0+/ 10.4 kg, post 52.7+/-10.7 kg) increased following the intervention. Fasting glucose concentrations did not change (p>0.05) following the intervention. However, 2-hr oral glucose tolerance improved in those with IGT (pre 8.94+/-0.72 mmol/l, post 7.83+/-1.11 mmol/l, p<0.05) and IFG/IGT (pre 9.66+/-1.11mmol/l, post 8.60+/-2.00 mmol/l) but not in those with IFG (pre 6.27+/-1.28mmol/l, post 6.33+/ 1.55 mmol/l). There were no significant changes in ISI or glucose area under the curve following the RT program. CONCLUSIONS: RT without dietary intervention improves 2-hr oral glucose tolerance in individuals with prediabetes. However, the improvements in glucose homeostasis with RT appear limited to those with IGT or combined IFG and IGT. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01112709. PMID- 26840907 TI - Maternal abdominal subcutaneous fat thickness as a predictor for adverse pregnancy outcome: a longitudinal cohort study. AB - OBJECTIVE: To assess maternal abdominal subcutaneous fat thickness (SFT) measured by ultrasound as an independent predictor of adverse pregnancy outcomes. DESIGN: A prospective longitudinal cohort study performed on pregnancies delivered between 2012 and 2014. SETTING: Sydney, Australia. POPULATION: About 1510 pregnant women attending routine obstetric ultrasounds. METHODS: Maternal SFT was measured on routine ultrasounds at 11-14 weeks' gestation (SFT1) and 18-22 weeks' gestation (SFT2). SFT measurements were assessed for estimating risks for obesity related pregnancy outcomes using logistic regression modelling adjusted for maternal age, parity, smoking status and body mass index (BMI). MAIN OUTCOME MEASURES: Hypertensive disease, gestational diabetes, caesarean section, low birthweight, preterm delivery, neonatal respiratory distress, Apgar scores, and admission to a neonatal intensive care unit. RESULTS: SFT1 and SFT2 were measured on 1461 and 1363 women, respectively. Mean thickness (range) were 21.2 mm (6.9 73.9) for SFT1 and 20.3 mm (7.5-68.0) for SFT2. Complete outcome data were available for 1385 pregnancies. In all, 54% of the women were overweight/obese. The SFT measures decreased from early to mid-pregnancy in overweight/obese women. There was moderate correlation between BMI and SFT1 (R(2) = 0.56) and BMI and SFT2 (R(2) = 0.55). In a multivariate model, SFT1 and SFT2 were better predictors for adverse pregnancy outcomes than BMI. CONCLUSION: Maternal SFT is a significant independent predictor of adverse pregnancy outcomes. Incorporation of SFT into future models for adverse pregnancy outcome may prove valuable. PMID- 26840908 TI - Image Guidance of Pleural Biopsies: Are Electromagnetic Waves Superior to Sound Waves? PMID- 26840906 TI - Three-dimensional MR spectroscopic imaging using adiabatic spin echo and hypergeometric dual-band suppression for metabolic mapping over the entire brain. AB - PURPOSE: Large lipid and water signals in MR spectroscopic imaging (MRSI) complicate brain metabolite quantification. In this study, we combined adiabatic hypergeometric dual-band (HGDB) lipid and water suppression with gradient offset independent adiabatic (GOIA) spin echo to improve three-dimensional (3D) MRSI of the entire brain. METHODS: 3D MRSI was acquired at 3T with a 32-channel coil. HGDB pulses were used before excitation and during echo time. A brain slab was selected with GOIA-W(16,4) pulses, weighted phase encoded stack of spirals, and real-time motion/shim correction. HGDB alone or in combination with OVS and MEGA (MEscher-GArwood) was compared with OVS only and no suppression. RESULTS: The combined HGDB pulses suppressed lipids to 2%-3% of their full unsuppressed signal. The HGDB lipid suppression was on average 5 times better than OVS suppression. HGDB+MEGA provided 30% more suppression compared with a previously described HGDB+OVS scheme. The number of voxels with good metabolic fits was significantly larger in the HGDB data (91%-94%) compared with the OVS data (59% 80%). CONCLUSION: HGDB pulses provided efficient lipid and water suppression for full brain 3D MRSI. The HGDB suppression is superior to traditional OVS, and it can be combined with adiabatic spin echo to provide a sequence that is robust to B1 inhomogeneity. Magn Reson Med 77:490-497, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26840909 TI - A-Disintegrin-And-Metalloproteinase (ADAM) 10 Activity on Resting and Activated Platelets. AB - The primary platelet collagen receptor, glycoprotein VI (GPVI), plays an important role in platelet activation and thrombosis. The ectodomain of human GPVI (sGPVI) is proteolytically shed from human platelets by a-disintegrin-and metalloproteinase 10 (ADAM10). In this study, we used a novel ADAM10-sensitive fluorescence resonance energy transfer sensor to analyze ADAM10-mediated shedding of GPVI from human platelets in response to the exposure of GPVI ligands collagen related peptide (10 MUg/mL), collagen (10 MUg/mL), and convulxin (0.1 MUg/mL) to shear stress (1000-10000 s(-1), 5 min), or a generic activator of metalloproteinases, N-ethylmaleimide (NEM, 5 mM). Elevated shear, NEM, or ligand engagement of GPVI all induced shedding of GPVI, as detected by release of sGPVI; however, only shear or NEM significantly increased ADAM10 enzyme activity. ADAM10 activity was also detectable on the surface of thrombi formed on a collagen coated surface under flow conditions. Our findings indicate different mechanisms regulate shear- and ligand-induced shedding and shear forces found within the vasculature can regulate ADAM10 activity. PMID- 26840910 TI - Identification of new FGF1 binding partners-Implications for its intracellular function. AB - Besides its classical mode of action through activation of specific receptors at the cell surface, fibroblast growth factor 1 (FGF1) can also cross the cellular membrane and translocate into the cytosol and further to the nucleus. The mechanism of this translocation is described partially, but the role of FGF1 inside the cell remains unknown. The aim of our work was to identify novel binding partners of FGF1 to predict its intracellular functions. We combined three methods of identification of such partners based on different principles: yeast two-hybrid screen and mass spectrometry (MS) analysis of complexes obtained by Tandem Affinity Purification (TAP) or by co-precipitation from cell lysate using recombinant FGF1. Altogether, we identified twenty novel intracellular proteins interacting with FGF1. For selected proteins, their direct interaction with FGF1 was confirmed by pull-down assays and SPR measurements. Interestingly, half of the proteins found are involved in processes related to cell viability, such as apoptosis, cell proliferation, and cell cycle regulation. Thus, our study indicates that the role of intracellular FGF1 is to protect the cell against stress conditions by providing an additional signal for cell survival, independently of receptor-activated signaling cascades. PMID- 26840911 TI - Help-seeking behaviour of patients with haematological malignancies treated with autologous stem cell transplantation. AB - Patients with haematological malignancies undergoing autologous stem cell transplantation face a life-threatening illness and stressful treatment. Although many patients report problems, relatively few patients report a need for additional professional care after treatment. We aimed to gain insight into the factors underlying this discrepancy by exploring patients' needs and help-seeking behaviour in relation to their experienced symptoms and problems. A qualitative research design following the grounded theory approach was used. Twenty patients, treated with autologous stem cell transplantation in the past 2 years, participated in an individual semi-structured interview. Factors contributing to patients' help-seeking behaviour were derived from our data and ordered in the following categories: (1) transition from symptoms to problems; (2) preference for dealing with problems themselves and with help from relatives; (3) problem categories and coping strategies; and (4) motives for (not) bringing in professional help. We concluded that the mere presence of a symptom does not lead to help-seeking behaviour: this relationship is modified by patients' personal goals, future perspective and phase of recovery. Patients seem to prefer to deal with problems without professional care. Patients' actual appeal for professional care depends on their coping strategies, social network and knowledge of available care. PMID- 26840912 TI - Morbidly obese and super-obese women should have surgery refused for benign conditions: AGAINST: Refusing surgery is both legally and morally wrong. PMID- 26840913 TI - Lumbopelvic muscle activation patterns in adolescent fast bowlers. AB - INTRODUCTION: Adolescent fast bowlers are prone to sustaining lumbar injuries. Numerous components have been identified as contributing factors; however, there is limited empirical evidence outlining how the muscles of the lumbopelvic region, which play a vital role in stabilising the spine, function during the bowling action and the influence of such activation on injuries in the fast bowler. METHODS: Surface electromyography was utilised to measure the function of the lumbar erector spinae, lumbar multifidus, gluteus medius and gluteus maximus muscles bilaterally during the fast bowling action in a group of 35 cricket fast bowlers aged 12-16 years. RESULTS: Two prominent periods of activation occurred in each of the muscles examined. The period of greatest mean activation in the erector spinae and multifidus occurred near back foot contact (BFC) and within the post-ball-release (BR) phase. The period of greatest mean activation for the gluteus medius and gluteus maximus occurred during phases of ipsilateral foot contact. DISCUSSION: The greatest periods of muscle activation in the paraspinal and gluteal muscles occurred at times where vertical forces were high such as BFC, and in the phases near BR where substantial shear forces are present. CONCLUSION: The posterior muscles within the lumbopelvic region appear to play a prominent role during the bowling action, specifically when compressive and shear forces are high. Further research is required to substantiate these findings and establish the role of the lumbopelvic muscles in the aetiology of lumbar injury in the cricket fast bowler. PMID- 26840915 TI - Use of n-of-1 (single patient) trials to assess the effect of age of transfused blood on health-related quality of life in transfusion-dependent patients. AB - BACKGROUND: The impact of age of red blood cells on health-related quality of life (HRQL) in patients who require chronic transfusions is not known. We assessed this using n-of-1 trials in patient populations where large randomized trials have not been done to date. STUDY DESIGN AND METHODS: Chronically transfusion-dependent adult patients were randomly assigned over time to four fresh (<7 days of storage) and four standard-issue (up to 42 days of storage) blood transfusions in prospective double-blinded multicrossover studies (n-of-1 trials). HRQL questionnaires were completed before and at 24 hours after each transfusion. Hemoglobin (Hb) levels were measured before each subsequent transfusion. RESULTS: Twenty transfusion-dependent patients were enrolled, of whom nine (five myelodysplastic syndromes, two myelofibrosis, one beta thalassemia major, one Diamond-Blackfan anemia) completed at least six transfusions. Mean ages of fresh and standard-issue blood transfused were 4.0 and 23.2 days, respectively. There were no significant differences in the effect of standard and fresh blood on follow-up Hb levels or the eight HRQL dimensions assessed in all analyses. CONCLUSIONS: In chronically transfused patients, there were no significant differences in HRQL or Hb levels between fresh versus standard blood. While larger trials are needed, these results support current practices in hospital blood transfusion laboratories using a first-in, first-out model of blood utilization for these transfusion-dependent patients. Use of n-of 1 trials to determine the benefits of transfusions in single patients appears to be feasible. PMID- 26840916 TI - Clinical provision of improvised nasal naloxone without experimental testing and without regulatory approval: imaginative shortcut or dangerous bypass of essential safety procedures? AB - CONTEXT: Take-home naloxone is increasingly provided to prevent heroin overdose deaths. Naloxone 0.4-2.0 mg is licensed for use by injection. Some clinicians supply improvised nasal naloxone kits (outside licensed approval). Is this acceptable? AIMS: (1) To consider provision of improvised nasal naloxone in clinical practice and (2) to search for evidence for pharmacokinetics and effectiveness (versus injection). METHODS: (1) To document existing nasal naloxone schemes and published evidence of pharmacokinetics (systematic search of the CINAHL, Cochrane, EMBASE and MEDLINE databases and 18 records included in narrative synthesis). (2) To analyse ongoing studies investigating nasal naloxone (WHO International Clinical Trials Registry Platform and US NIH RePORT databases). FINDINGS: (1) Multiple studies report overdose reversals following administration of improvised intranasal naloxone. (2) Overdose reversal after nasal naloxone is frequent but may not always occur. (3) Until late 2015, the only commercially available naloxone concentrations were 0.4 mg/ml and 2 mg/2 ml. Nasal medications are typically 0.05-0.25 ml of fluid per nostril. The only published study of pharmacokinetics and bioavailability finds that nasal naloxone has poor bioavailability. QUESTIONS FOR DEBATE: (1) Why are pharmacokinetics and bioavailability data for nasal naloxone not available before incorporation into standard clinical practice? (2) Does nasal naloxone have the potential to become a reliable clinical formulation? (3) What pre-clinical and clinical studies should precede utilization of novel naloxone formulations as standard emergency medications? CONCLUSIONS: The addictions treatment field has rushed prematurely into the use of improvised nasal naloxone kits. Evidence of adequate bioavailability and acceptable pharmacokinetic curves are vital preliminary steps, especially when effective approved formulations exist. PMID- 26840917 TI - Dispelling myths concerning pigmented skin lesions. AB - The history of medicine is replete with examples of debunked myths, and in daily clinical dermatological practice, we must still counter many misconceptions regarding pigmented lesions, both with patients and other medical practitioners. Debunking myths and attempting to explain the reasons for these erroneous beliefs are the purposes of this review. The literature review has been partially guided by the results obtained from an online questionnaire conducted on an Italian website (www.vediamocichiara.it) from February 15, 2015 to March 15, 2015. The remaining discussed were selected on the basis of the existing literature and our personal experience. In order to explore these misconceptions, the following are the seven most salient questions that require investigation: (i) Is it dangerous to excise moles?; (ii) Is it dangerous to traumatize moles?; (iii) Are plantar moles worrisome?; (iv) Is it necessary to selectively apply sunscreen to moles?; (v) Is it inadvisable to partially biopsy a melanoma?; (vi) Do moles turn into melanoma?; and (vii) Is it necessary to perform sentinel lymph node biopsy for thin melanomas and for atypical Spitz naevi? Myths are ubiquitous, being prevalent in dermatological practice, with many of them concerning pigmented skin lesions. By encouraging critical analysis by patients and medical practitioners, the birth and perpetuation of myths can potentially be minimized, for the ultimate benefit of patients. This requires a scientific approach to be rigorously applied to dermatology, with critical questioning of unsubstantiated hypotheses including those emanating from the mass media as well as from respected sources. PMID- 26840918 TI - Exploring the unknown: electrophysiological and behavioural measures of visuospatial learning. AB - Visuospatial memory describes our ability to temporarily store and manipulate visual and spatial information and is employed for a wide variety of complex cognitive tasks. Here, a visuospatial learning task requiring fine motor control is employed to investigate visuospatial learning in a group of typically developing adults. Electrophysiological and behavioural data are collected during a target location task under two experimental conditions: Target Learning and Target Cued. Movement times (MTs) are employed as a behavioural metric of performance, while dynamic P3b amplitudes and power in the alpha band (approximately 10 Hz) are explored as electrophysiological metrics during visuospatial learning. Results demonstrate that task performance, as measured by MT, is highly correlated with P3b amplitude and alpha power at a consecutive trial level (trials 1-30). The current set of results, in conjunction with the existing literature, suggests that changes in P3b amplitude and alpha power could correspond to different aspects of the learning process. Here it is hypothesized that changes in P3b correspond to a diminishing inter-stimulus interval and reduced stimulus relevance, while the corresponding changes in alpha power represent an automation of response as habituation occurs in participants. The novel analysis presented in the current study demonstrates how gradual electrophysiological changes can be tracked during the visuospatial learning process under the current paradigm. PMID- 26840919 TI - Validation of an automated enzyme immunoassay for the measurement of serum total thyroxine in cats. AB - BACKGROUND: Hyperthyroidism is common in older cats, which necessitates frequent screening of serum total thyroxine (TT4) concentrations. Fast, cheap, and reliable methods to measure TT4 in cats are needed. OBJECTIVES: The purpose of the study was the validation of a human TT4 enzyme immunoassay (EIA) for use with feline serum, and derivation of a TT4 reference interval (RI) for cats aged 9 years and older. METHODS: Assay precision, reproducibility, and linearity were evaluated. Interference by hemolysis was also assessed. Method comparison studies between the human EIA and a previously validated radioimmunoassay (RIA) and chemiluminescent-enzyme immunoassay (CEIA) were performed. Healthy cats (> 9 years) were recruited from 3 UK first opinion practices. RESULTS: The human TT4 EIA demonstrated good precision and reproducibility, and adequate linearity. Hemolysis did not significantly alter measured TT4 concentrations until HGB > 8 g/L. Method comparison revealed proportional and constant errors between EIA and RIA/CEIA. The TT4 RI for cats (> 9 years) was calculated as 7.1-45.1 nmol/L (n = 49). CONCLUSIONS: The human TT4 EIA was successfully validated for use with feline serum and offers a rapid, cheap, and reliable method for determination of serum TT4 concentrations in cats. PMID- 26840920 TI - Arteriolar Diameters in Glaucomatous Eyes with Single-Hemifield Damage. AB - PURPOSE: To examine the association between retinal arteriolar caliber and lumen, retinal sensitivity (RS), and retinal nerve fiber layer (RNFL) thickness in glaucomatous eyes with single-hemifield loss. METHODS: We conducted a prospective, nonrandomized, case-control study of 20 eyes of 20 patients with glaucoma with visual field damage confined to a single hemifield. The control group was composed of 20 eyes of 20 normal subjects. For all the eyes, we performed optical coherence tomography to assess the RNFL and standard automated perimetry to evaluate RS. External and internal arteriolar diameters were assessed in vivo using scanning laser Doppler flowmetry. RESULTS: The RNFL was significantly thinner in glaucomatous eyes than in normal eyes (p < 0.001). In glaucomatous eyes, a positive correlation between sectorial RNFL thickness and the corresponding external and internal arteriolar diameters was found (r = 0.43, p = 0.05; r = 0.63, p = 0.003, respectively). The internal arteriolar diameter significantly correlated with RS in the corresponding abnormal hemifield (r = 0.44, p = 0.04). Compared with the normal hemifield, the internal arteriolar diameter, RNFL thickness, and RS were significantly reduced, whereas the external arteriolar diameter was unchanged in the abnormal hemifield. CONCLUSIONS: In glaucomatous eyes with single-hemifield damage, attenuation of retinal vessels was associated with a thinner RNFL and reduced RS. Moreover, a narrower lumen with increased wall-to-lumen ratio was found in the abnormal hemifield, supporting the hypothesis that vessel narrowing is likely secondary to a lower demand for blood flow in the glaucomatous areas of the retina. PMID- 26840921 TI - Celebrating hearing loss prevention. PMID- 26840922 TI - Speech recognition in noise under hearing protection: A computational study of the combined effects of hearing loss and hearing protector attenuation. AB - OBJECTIVE: To investigate the effects of hearing protection on speech recognition in noise. DESIGN: Computational study using a speech recognition model that was previously empirically validated. STUDY SAMPLE: Recognition scores were calculated in unprotected and protected conditions for four sets of hearing protector attenuation functions in two different noises, for three simulated hearing profiles illustrative of those anticipated in the noisy workplace. RESULTS: For a normal-hearing profile, recognition scores were not sensitive to the slope of the attenuation function and the overall amount of noise reduction, but protected conditions provided a small but consistent 7-12% benefit compared to unprotected listening. For profiles simulating hearing loss, recognition scores were much more sensitive to the attenuation function. Substantial drops of 30% or more were found compared to unprotected listening in some conditions of steep attenuation slopes and large noise reductions. Attenuation functions modelled from real hearing protectors with nearly-flat attenuation yielded a benefit compared to unprotected listening for all hearing profiles studied. These findings were true in both noises. CONCLUSIONS: Limiting the slope of the hearing protector attenuation function and/or the overall amount of noise reduction is useful and warranted for workers with hearing loss to prevent adverse effects on speech recognition. PMID- 26840923 TI - Auditory risk of air rifles. AB - OBJECTIVE: To characterize the impulse noise exposure and auditory risk for air rifle users for both youth and adults. DESIGN: Acoustic characteristics were examined and the auditory risk estimates were evaluated using contemporary damage risk criteria for unprotected adult listeners and the 120-dB peak limit and LAeq75 exposure limit suggested by the World Health Organization (1999) for children. STUDY SAMPLE: Impulses were generated by nine pellet air rifles and one BB air rifle. RESULTS: None of the air rifles generated peak levels that exceeded the 140 dB peak limit for adults, and eight (80%) exceeded the 120 dB peak SPL limit for youth. In general, for both adults and youth, there is minimal auditory risk when shooting fewer than 100 unprotected shots with pellet air rifles. Air rifles with suppressors were less hazardous than those without suppressors, and the pellet air rifles with higher velocities were generally more hazardous than those with lower velocities. CONCLUSION: To minimize auditory risk, youth should utilize air rifles with an integrated suppressor and lower velocity ratings. Air rifle shooters are advised to wear hearing protection whenever engaging in shooting activities in order to gain self-efficacy and model appropriate hearing health behaviors necessary for recreational firearm use. PMID- 26840926 TI - The influence of funding sources on the scientific method. PMID- 26840928 TI - MC3T3-E1 Cell Response to Ti1-xAgx and Ag-TiNx Electrodes Deposited on Piezoelectric Poly(vinylidene fluoride) Substrates for Sensor Applications. AB - In the sensors field, titanium based coatings are being used for the acquisition/application of electrical signals from/to piezoelectric materials. In this particular case, sensors are used to detect dynamic mechanical loads at early stages after intervention of problems associated with prostheses implantation. The aim of this work is to select an adequate electrode for sensor applications capable, in an initial stage to avoid bone cell adhesion, but at a long stage, permit osteointegration and osteoinduction. This work reports on the evaluation of osteoblast MC3T3-E1 cells behavior in terms of proliferation, adhesion and long-term differentiation of two different systems used as sensor electrodes: Ti1-xAgx and Ag-TiNx deposited by d.c. and pulsed magnetron sputtering at room temperature on poly(vinylidene fluoride) (PVDF). The results indicated an improved effect of Ag-TiNx electrodes compared with Ti1-xAgx and TiN, in terms of diminished cell adhesion and proliferation at an initial cell culture stage. Nevertheless, when cell culture time is longer, cells grown onto Ag-TiNx electrodes are capable to proliferate and also differentiate at proper rates, indicating the suitability of this coating for sensor application in prostheses devices. Thus, the Ag-TiNx system was considered the most promising electrode for tissue engineering applications in the design of sensors for prostheses to detect dynamic mechanical loads. PMID- 26840929 TI - The neuroprotective potential of arginine-rich peptides for the acute treatment of traumatic brain injury. PMID- 26840927 TI - Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients. AB - Presensitized kidney transplant recipients are at high-risk for early antibody mediated rejection. We studied the impact of pre- and post-transplant donor specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR-GL (86 vs 0 vs 0%; log-rank P < 0.001) compared with post transplant DSA without C1q-binding or the absence of DSA. Patients with both pre transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post transplant. PMID- 26840931 TI - Essential role of Wnt5a-Ror1/Ror2 signaling in metanephric mesenchyme and ureteric bud formation. AB - Spatiotemporally regulated interaction between the metanephric mesenchyme (MM) and Wolffian duct (WD) is essential for the induction of a single ureteric bud (UB). The MM then interacts with the tip of the UB to induce outgrowth and branching of the UB, which in turn promotes growth of the adjacent MM. The Ror family receptor tyrosine kinases, Ror1 and Ror2, have been shown to act as receptors for Wnt5a to mediate noncanonical Wnt signaling. Previous studies have shown that Ror2-mutant mice exhibit ectopic formation of the UB, due to abnormal juxtaposition of the MM to the WD. We show here that both Ror1 and Ror2 are expressed in the mesenchyme between the MM and WD during UB formation. Although Ror1-mutant mice show no apparent defects in UB formation, Ror1;Ror2-double mutant mice exhibit either defects in UB outgrowth and branching morphogenesis, associated with the loss of the MM from the UB domain, or ectopic formation of the UB. We also show genetic interactions between Ror1 and Wnt5a during UB formation. These findings suggest that Wnt5a-Ror1/Ror2 signaling regulates cooperatively the formation of the MM at the proper position to ensure normal development of the UB. PMID- 26840932 TI - [Not Available]. AB - A new, dynamic concept of health, which aims to convince critics of the static WHO definition of 1948, was based on an invitational conference in 2009. The concept highlights function, resilience and self-direction. This general concept of health was further elaborated in a follow-up study aiming towards operationalization, and involving Dutch healthcare stakeholder groups. The study revealed a number of differences between the opinions of stakeholder groups about the concept of health and, following the perception of patients, resulted in the broad concept of 'positive health' with six dimensions. PMID- 26840933 TI - [Porphyria cutanea tarda: the benefit of additional diagnostics]. AB - The porphyrias are a clinically and genetically heterogeneous group of relatively rare metabolic diseases that result from disorders in the biosynthesis of haeme. Porphyria cutanea tarda (PCT) is the most common type, accounting for 80-90% of all porphyrias, and is essentially an acquired disease, although PCT can also occur on a familial basis. We describe a 71-year-old female and a 62-year-old male patient, both of whom had several risk factors for developing PCT, ranging from iron overload due to a mutation in the hereditary haemochromatosis protein (HFE) gene, alcohol use, smoking, and exogenous oestrogen, to persistent hepatitis C infection. The clinical relevance of the several diagnostic modalities is important in PCT. Diagnostic evaluation is important in order to confirm the diagnosis, but also to evaluate the treatment response in the context of long-term follow-up in the prevention of late complications of PCT, i.e. hepatocellular carcinoma. PMID- 26840934 TI - [A neonate with pustules]. AB - We describe a female neonate with non-grouped pustules directly postpartum without clinical signs of illness. There were no red maculae. At follow-up some pustules had turned to pigmented maculae, which confirmed the diagnosis of neonatal pustular melanosis. This benign transient condition occurs in 4-8% of dark-coloured neonates and in <1% of white neonates. PMID- 26840935 TI - [Agranulocytosis and septic shock after metamizole use]. AB - BACKGROUND: Metamizole is an analgesic, the orally administered form of which was withdrawn in the Netherlands in 1989 due to an unacceptably high incidence of agranulocytosis. However, later studies showed a much lower incidence and since 2013 the use of metamizole has been recommended by the national guideline on postoperative pain. CASE DESCRIPTION: A 58-year-old woman was referred by her general practitioner to our hospital with suspected diverticulitis. Three days previously the patient had returned from a four-week period of rehabilitation at a German spa following hip replacement surgery. She had been using metamizole since the operation. Within hours of admission, the patient developed septic shock and was transferred to the intensive care unit. Laboratory tests revealed severe neutropenia of 0.2 * 10(9)/l. Treatment consisted of filgrastim, piperacillin/tazobactam and haemodynamic support. After five days the patient was sufficiently recovered to return to the ward. CONCLUSION: Metamizole-related agranulocytosis is rare but potentially life-threatening. This condition is expected to occur more frequently as the use of metamizole in the Netherlands increases. PMID- 26840936 TI - [A young woman with abnormal vaginal tissue loss]. AB - A 18-year-old woman experienced abnormal and painful vaginal tissue loss while using an oral contraceptive. A pregnancy test was negative. Histopathological examination of the tissue showed a decidualised endometrium. We made the diagnosis of progesterone-induced membranous dysmenorrhoea. PMID- 26840937 TI - [Unstable angina: a diagnosis of the past]. AB - The diagnosis acute coronary syndrome includes myocardial infarction together with unstable angina. The definition of the latter diagnosis continues to evolve. Due to widespread clinical application of sensitive markers of myocardial necrosis, including high sensitive cardiac troponin (hs-cTn) assays, the diagnosis for many newly presenting patients will now be myocardial infarction rather than unstable angina. However, patients presenting with chest pain and very low (< 0.05 ng/L) or undetectable levels of hs-cTn have been found to be at extremely low risk of development of myocardial infarction and/or death. Consequently, such patients cannot be classified as having unstable angina. A detailed clinical assessment and reasoning will be necessary to establish the true cause of their--often non-cardiac--symptoms. PMID- 26840938 TI - [Severe erythema and pustules after antibiotic use: acute generalised exanthematous pustulosis]. AB - BACKGROUND: Acute generalised exanthematous pustulosis (AGEP) is a rare and self limiting pustular cutaneous reaction to a drug or infection. CASE DESCRIPTION: A 62-year-old male presented to the Emergency Department with fever, erythema and pustules on both thighs. The initial blood analysis showed increased inflammatory parameters. The patient was admitted to the Dermatology Department with suspected AGEP. All medication was stopped. The diagnosis was confirmed histologically. During hospitalisation, the cutaneous reaction spread over 30% of the skin surface. Seven days after onset, the skin disorder regressed and the patient was discharged after 16 days. Use of amoxicillin/clavulanic acid was very likely the triggering factor for the development of AGEP. CONCLUSION: AGEP, although self limiting, can have a fulminant course, requiring admission to a burns centre. It is imperative that rechallenge with the triggering drug is avoided. PMID- 26840939 TI - [The End-of-life Clinic: results from the first year]. AB - In 2012 the Dutch Dying with Dignity Society (NVVE) founded the End-of-life Clinic, which provides euthanasia or help with assisted suicide at the request of people whose own doctor will not carry out euthanasia if the legal requirements of due care can been fulfilled. As part of an independent evaluation, we looked at the applications received by the End-of-life Clinic during its first year and at the outcomes of these applications. We wrote an extensive article on this subject which was published in JAMA Internal Medicine. One of the most important outcomes is that the End-of-life Clinic rejected a large percentage of the requests for its services, mainly as these came from people with psychiatric conditions. This means that the fears that some people have concerning the alleged End-of-life Clinic policy 'you ask, we comply', appear to be unfounded. On the other hand, the End-of-life Clinic is certainly not the solution for all those people whose requests to their own doctor fall on deaf ears. PMID- 26840940 TI - Quadruplex Nucleic Acids as Novel Therapeutic Targets. AB - Quadruplex-forming sequences are widely prevalent in human and other genomes, including bacterial ones. These sequences are over-represented in eukaryotic telomeres, promoters, and 5' untranslated regions. They can form quadruplex structures, which may be transient in many situations in normal cells since they can be effectively resolved by helicase action. Mutated helicases in cancer cells are unable to unwind quadruplexes, which are impediments to transcription, translation, or replication, depending on their location within a particular gene. Small molecules that can stabilize quadruplex structures augment these effects and produce cell and proliferation growth inhibition. This article surveys the chemical biology of quadruplexes. It critically examines the major classes of quadruplex-binding small molecules that have been developed to date and the various approaches to discovering selective agents. The challenges of requiring (and achieving) small-molecule targeted selectivity for a particular quadruplex are discussed in relation to the potential of these small molecules as clinically useful therapeutic agents. PMID- 26840941 TI - CO2-Induced Phase Engineering: Protocol for Enhanced Photoelectrocatalytic Performance of 2D MoS2 Nanosheets. AB - Molybdenum disulfide (MoS2) is a promising non-precious-metal catalyst, but its performance is limited by the density of active sites and poor electrical transport. Its metallic 1T phase possesses higher photoelectrocatalytic activity. Thus, how to efficiently increase the concentration of the 1T phase in the exfoliated two-dimensiaonal (2D) MoS2 nanosheets is an important premise. In this work, we propose a strategy to prepare a 2D heterostructure of MoS2 nanosheets using supercritical CO2-induced phase engineering to form metallic 1T-MoS2. Theoretical calculations and experimental results demonstrate that the introduced CO2 in the 2H-MoS2 host can prompt the transformation of partial 2H-MoS2 lattices into 1T-MoS2. Moreover, the electrical coupling and synergistic effect between 2H and 1T phases can greatly facilitate the efficient electron transfer from the active sites of MoS2, which significantly improves the photocatalytic performance. PMID- 26840942 TI - Mechanistic Differences Leading to Infectious and Sterile Inflammation. AB - Inflammation is a physiologic component of pregnancy and parturition. Overwhelming intrauterine inflammatory load promotes quiescent feto-maternal tissues into a contractile phenotype. Like inflammation, oxidative stress is an inevitable component of both pregnancy and parturition. Pathologic activation of host innate immune response to adverse pregnancy conditions can lead to premature activation of inflammatory and oxidative stress. Inflammation and oxidative stress markers seen with both sterile and infectious inflammation are often similar; therefore, it is difficult to understand causality of conditions like spontaneous preterm birth. This review demonstrates potential mechanistic pathways of activation of sterile and infectious inflammation. We demonstrate the activation of two unique pathways of inflammation by factors that are well documented proxies for oxidative stress (cigarette smoke extract) and infection (lipopolysaccharide). Sterile inflammation seen after exposure to an oxidative stress inducer is due to cellular elemental damage resulting in p38 mitogen activated protein kinase (MAPK) induced cellular senescence. Infectious inflammation is through activation of transcription factor NF-kappaB and independent of oxidative stress-associated damages and p38 MAPK-induced senescence. Understanding the differences in the inflammatory pathway activation by various risk factors is important to design better screening, diagnostic and intervention strategies to reduce the risks of adverse pregnancy outcomes. PMID- 26840943 TI - IGF/STAT3/NANOG/Slug Signaling Axis Simultaneously Controls Epithelial Mesenchymal Transition and Stemness Maintenance in Colorectal Cancer. AB - Discovery of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) are two milestones in people exploring the nature of malignant tumor in recent decades. Although some studies have presented the potential connections between them, the link details, underneath their superficial correlation, are largely unknown. In this study, we identified a small subpopulation of NANOG-positive colorectal cancer (CRC) cells, and demonstrated that they exhibited characteristics of CSCs and EMT traits simultaneously. Furthermore, we found that NANOG was a core factor in regulating both of EMT and stemness in CRC cells, NANOG modulate EMT and metastasis by binding to Slug promoter and transcriptionally regulate Slug expression. For the first time, we demonstrated that NANOG was regulated by extracellular IGF signaling pathway via STAT3 phosphorylation in CRC. This coincides with that IGF receptor IGF-1R is often increasing expressed in malignant metastasis colon cancer. Taken together, our data define the crucial functions of IGF/STAT3/NANOG/Slug signaling axis in the progression of CRC by operating EMT and CSCs properties, which make them served as potential therapeutic targets for treatment of CRC. PMID- 26840945 TI - Analytical calculation of proton linear energy transfer in voxelized geometries including secondary protons. AB - In order to integrate radiobiological modelling with clinical treatment planning for proton radiotherapy, we extended our in-house treatment planning system FoCa with a 3D analytical algorithm to calculate linear energy transfer (LET) in voxelized patient geometries. Both active scanning and passive scattering delivery modalities are supported. The analytical calculation is much faster than the Monte-Carlo (MC) method and it can be implemented in the inverse treatment planning optimization suite, allowing us to create LET-based objectives in inverse planning. The LET was calculated by combining a 1D analytical approach including a novel correction for secondary protons with pencil-beam type LET kernels. Then, these LET kernels were inserted into the proton-convolution superposition algorithm in FoCa. The analytical LET distributions were benchmarked against MC simulations carried out in Geant4. A cohort of simple phantom and patient plans representing a wide variety of sites (prostate, lung, brain, head and neck) was selected. The calculation algorithm was able to reproduce the MC LET to within 6% (1 standard deviation) for low-LET areas (under 1.7 keV MUm(-1)) and within 22% for the high-LET areas above that threshold. The dose and LET distributions can be further extended, using radiobiological models, to include radiobiological effectiveness (RBE) calculations in the treatment planning system. This implementation also allows for radiobiological optimization of treatments by including RBE-weighted dose constraints in the inverse treatment planning process. PMID- 26840944 TI - Randomized clinical trial comparing long-term quality of life for Billroth I versus Roux-en-Y reconstruction after distal gastrectomy for gastric cancer. AB - BACKGROUND: Patients' quality of life (QoL) deteriorates remarkably after gastrectomy. Billroth I reconstruction following distal gastrectomy has the physiological advantage of allowing food to pass through the duodenum. It was hypothesized that Billroth I reconstruction would be superior to Roux-en-Y reconstruction in terms of long-term QoL after distal gastrectomy. This study compared two reconstructions in a multicentre prospective randomized clinical trial to identify the optimal reconstruction procedure. METHODS: Between January 2009 and September 2010, patients who underwent gastrectomy for gastric cancer were randomized during surgery to Billroth I or Roux-en-Y reconstruction. The primary endpoint was assessment of QoL using the Functional Assessment of Cancer Therapy - Gastric (FACT-Ga) questionnaire 36 months after surgery. RESULTS: A total of 122 patients were enrolled in the study, 60 to Billroth I and 62 to Roux en-Y reconstruction. There were no differences between the two groups in terms of postoperative complications or mortality, and no significant differences in FACT Ga total score (P = 0.496). Symptom scales such as epigastric fullness (heaviness), diarrhoea and fatigue were significantly better in the Billroth I group at 36 months after gastrectomy (heaviness, P = 0.040; diarrhoea, P = 0.046; fatigue, P = 0.029). The rate of weight loss in the third year was lower for patients in the Billroth I group (P = 0.046). CONCLUSION: The choice of anastomotic reconstruction after distal gastrectomy resulted in no difference in long-term QoL in patients with gastric cancer. REGISTRATION NUMBER: NCT01065688 (http://www.clinicaltrials.gov). PMID- 26840946 TI - Evidence for Anionic Excess Electrons in a Quasi-Two-Dimensional Ca2N Electride by Angle-Resolved Photoemission Spectroscopy. AB - Angle-resolved photoemission spectroscopy (ARPES) study of a layered electride Ca2N was carried out to reveal its quasi-two-dimensional electronic structure. The band dispersions and the Fermi-surface map are consistent with the density functional theory results except for a chemical potential shift that may originate from the high reactivity of surface excess electrons. Thus, the existence of anionic excess electrons in the interlayer region of Ca2N is strongly supported by ARPES. PMID- 26840948 TI - Synthesis of (Ga1-xZnx)(N1-xOx) with Enhanced Visible-Light Absorption and Reduced Defects by Suppressing Zn Volatilization. AB - (Ga1-xZnx)(N1-xOx) (GZNO) particles with enhanced optical absorption were synthesized by topotactic transformation of Zn(2+)/Ga(3+) layered double hydroxides. This outcome was achieved by suppressing Zn volatilization during nitridation by maintaining a low partial pressure of O2 (pO2). Zn-rich (x > (1)/3) variants of GZNO were achieved and compared to those prepared by conventional ammonoylsis conditions. The optical absorption and structural properties of these samples were compared to those prepared in the absence of O2 by diffuse-reflectance spectroscopy and powder X-ray diffraction methods. Notably, suppression of Zn volatilization leads to smaller-band-gap materials (2.30 eV for x = 0.42 versus 2.71 eV for x = 0.21) and reduced structural defects. This synthetic route and set of characterizations provide useful structure-property studies of GZNO and potentially other oxynitrides of interest as photocatalysts. PMID- 26840947 TI - Mapping the Flavor Contributing Traits on "Fengwei Melon" (Cucumis melo L.) Chromosomes Using Parent Resequencing and Super Bulked-Segregant Analysis. AB - We used a next-generation high-throughput sequencing platform to resequence the Xinguowei and Shouxing melon cultivars, the parents of Fengwei melon. We found 84% of the reads (under a coverage rate of "13*") placed on the reference genome DHL92. There were 2,550,000 single-nucleotide polymorphisms and 140,000 structural variations in the two genomes. We also identified 1,290 polymorphic genes between Xinguowei and Shouxing. We combined specific length amplified fragment sequencing (SLAF-seq) and bulked-segregant analysis (super-BSA) to analyze the two parents and the F2 extreme phenotypes. This combined method yielded 12,438,270 reads, 46,087 SLAF tags, and 4,480 polymorphic markers (average depth of 161.81*). There were six sweet trait-related regions containing 13 differential SLAF markers, and 23 sour trait-related regions containing 48 differential SLAF markers. We further fine-mapped the sweet trait to the genomic regions on chromosomes 6, 10, 11, and 12. Correspondingly, we mapped the sour trait-related genomic regions to chromosomes 2, 3, 4, 5, 9, and 12. Finally, we positioned nine of the 61 differential markers in the sweet and sour trait candidate regions on the parental genome. These markers corresponded to one sweet and eight sour trait-related genes. Our study provides a basis for marker assisted breeding of desirable sweet and sour traits in Fengwei melons. PMID- 26840950 TI - Characterization of ST258 Colistin-Resistant, blaKPC-Producing Klebsiella pneumoniae in a Greek Hospital. AB - The emergence of colistin resistance may further contribute to treatment failure of infection caused by multidrug-resistant (MDR) Klebsiella pneumoniae. The colistin resistance rates were determined and colistin-resistant carbapenemase producing K. pneumoniae (COL-R CP-Kp) were characterized over an 18-month period in a Greek hospital. Out of 135 carbapenemase producers, 19 isolates (14%) were categorized as resistant to colistin. Phenotypic and molecular characterization of the COL-R CP-Kp isolates revealed that all were MDR blaKPC producers and, excluding one isolate of MLST ST383, belonged to the international clonal lineage ST258. Furthermore, PCR amplification and sequencing of the mgrB locus revealed nucleotide sequences of different sizes and insertions of IS1- and IS5-like mobile elements. The majority (63%) of the COL-R blaKPC producers was recovered from patients in the intensive care unit (ICU) and clinical data indicated that all patients should have acquired these isolates in the ICU. The findings of the present study underscore a concerning evolution of colistin resistance in a setting of high K. pneumoniae carbapenemase (KPC)-Kp endemicity, such as Greece. Thus, continuous surveillance, molecular characterization, prudent use of antibiotics, and implementation of infection control measures for K. pneumoniae are urgent. PMID- 26840951 TI - Extensive Field Survey, Laboratory and Greenhouse Studies Reveal Complex Nature of Pseudomonas syringae-Associated Hazelnut Decline in Central Italy. AB - Pseudomonas avellanae (Pav) has been reported as the causal agent of bacterial decline and bacterial canker of hazelnut in Italy and Greece, respectively. Both hazelnut diseases were reported to be similar in terms of symptoms, severity and persistence. In this study, we found that both symptomatic and asymptomatic trees in the field were colonized by Pav. Multilocus Sequence Typing (MLST) analysis showed that Pav strains isolated during this study in Italy belong to the P. syringae phylogroup 1 and they are closely related to Pav strains previously isolated in Greece from hazelnut bacterial canker. On the other hand, strains isolated in earlier studies from hazelnut decline in Italy belong to both phylogroup 1 and 2 of P. syringae. Both phylogroup 1 strains of P. syringae from Greece and Italy are different than strains isolated in this study in terms of their capacity to excrete fluorescent pigments on different media. Despite the same plant genotype and cropping practices adopted, the incidence of hazelnut decline ranged from nearly 0 to 91% across our study sites. No disease developed on plants inoculated with Pav through wounding while leaf scar inoculations produced only mild disease symptoms. Based on our results and the previously reported correlation between pedo-climatic conditions and hazelnut decline, we conclude that hazelnut decline in central Italy could be incited by a combination of predisposing (adverse pedo-climatic conditions) and contributing factors (Pav). Because this is a true decline different from "bacterial canker" described in Greece, we refer to it as hazelnut decline (HD). PMID- 26840953 TI - Species Diversity in the Parasitoid Genus Asobara (Hymenoptera: Braconidae) from the Native Area of the Fruit Fly Pest Drosophila suzukii (Diptera: Drosophilidae). AB - Drosophila suzukii (Matsumura), commonly known as Spotted Wing Drosophila (SWD), is a worldwide serious economic threat to the production of berries and stone fruits. The chemical control widely used against this pest is often not able to preventing yield losses because wild flora offers an abundance of fruits to D. suzukii where the pest is able to reproduce and from where it recolonizes neighbouring cultivated fields. Alternatively, within Integrated Pest Management protocols for D. suzukii, biological control could play a key role by reducing its populations particularly in non-cultivated habitats, thus increasing the effectiveness and reducing the side negative effects of other management strategies. Because of the scarcity and of the low efficiency of autochthonous parasitoids in the new invaded territories, in the last few years, a number of surveys started in the native area of D. suzukii to find parasitoid species to be evaluated in quarantine structures and eventually released in the field, following a classical biological control approach. This paper reports the results of these surveys carried out in South Korea and for the first time in China. Among the parasitoids collected, those belonging to the genus Asobara Foerster resulted dominant both by number and species diversity. By combining morphological characters and the mitochondrial COI gene as a molecular marker, we identified seven species of Asobara, of which two associated with D. suzukii, namely A. japonica and A leveri, and five new to science, namely Asobara brevicauda, A. elongata, A mesocauda, A unicolorata, A. triangulata. Our findings offer new opportunity to find effective parasitoids to be introduced in classical biological control programmes in the territories recently invaded by D. suzukii. PMID- 26840952 TI - Recombinant Factor IX Fc Fusion Protein Maintains Full Procoagulant Properties and Exhibits Prolonged Efficacy in Hemophilia B Mice. AB - INTRODUCTION: Hemophilia B is an inherited X chromosome-linked disorder characterized by impaired blood clotting owing to the absence of functional coagulation factor IX. Due to the relatively short half-life of factor IX, patients with hemophilia B require frequent factor IX infusions to maintain prophylaxis. We have developed a recombinant factor IX (rFIX) fused to the Fc region of IgG (rFIXFc) with an extended half-life in animals and humans. MATERIALS AND METHODS: Procoagulant properties of rFIXFc and rFIX (BENEFIX(r)) were compared to determine the effect of the Fc region on rFIXFc hemostatic function. Specifically, we assessed rFIXFc activation, intermolecular interactions within the Xase complex, inactivation by antithrombin III (AT) and thrombin generation potential compared with rFIX. We also assessed the acute and prophylactic efficacy profiles of rFIXFc and rFIX in vivo in hemophilia B mouse bleeding models. RESULTS AND CONCLUSIONS: The activation by factor XIa or factor VIIa/tissue factor, inhibition by AT, interaction profiles with phospholipids, affinities for factor VIIIa within the context of the Xase complex, and thrombin generation profiles were similar for rFIXFc and rFIX. Xase complexes formed with either molecule exhibited similar kinetic profiles for factor Xa generation. In acute efficacy models, mice infused with rFIXFc or rFIX were equally protected from bleeding. However, in prophylactic efficacy models, protection from bleeding was maintained approximately three times longer in rFIXFc-dosed mice than in those given rFIX; this prolonged efficacy correlates with the previously observed half-life extension. We conclude that rFIXFc retains critical FIX procoagulant attributes and that the extension in rFIXFc half-life translates into prolonged efficacy in hemophilia B mice. PMID- 26840954 TI - Triggering Dectin-1-Pathway Alone Is Not Sufficient to Induce Cytokine Production by Murine Macrophages. AB - beta-glucans (BG) are abundant polysaccharides of the Saccharomyces cerevisiae cell wall (Sc CW), an industry byproduct. They have immuno-stimulatory properties upon engagement of dectin-1 (Clec7a), their main receptor on particular immune cells, and they actually become of great interest because of their preventive or therapeutic potentials. Zymosan, a crude extract of Sc CW was studied as a prototypic BG, despite its miscellaneous PAMPs content. Here, we examined the response of murine wild type or Clec7a-/- bone marrow-derived macrophages (BMDM) to products with increasing BG content (15, 65 or 75%) and compared their effects with those of other dectin-1 ligands. The enrichment process removed TLR ligands while preserving dectin-1 activity. The most enriched extracts have very low NFkappaB activity and triggered low amounts of cytokine production in contrast with crude products like zymosan and BG15. Furthermore, MyD88-/- BMDM did not produce TNFalpha in response to crude Sc CW extracts, whereas their response to BG-enriched extracts was unaffected, suggesting that BG alone are not able to initiate cytokine secretion. Although Sc CW-derived BG stimulated the late and strong expression of Csf2 in a dectin-1-dependent manner, they remain poor inducers of chemokine and cytokine production in murine macrophages. PMID- 26840955 TI - Biomaterial-Enhanced Cell and Drug Delivery: Lessons Learned in the Cardiac Field and Future Perspectives. AB - Heart failure is a significant clinical issue. It is the cause of enormous healthcare costs worldwide and results in significant morbidity and mortality. Cardiac regenerative therapy has progressed considerably from clinical and preclinical studies delivering simple suspensions of cells, macromolecule, and small molecules to more advanced delivery methods utilizing biomaterial scaffolds as depots for localized targeted delivery to the damaged and ischemic myocardium. Here, regenerative strategies for cardiac tissue engineering with a focus on advanced delivery strategies and the use of multimodal therapeutic strategies are reviewed. PMID- 26840957 TI - Human-Induced Landscape Changes Homogenize Atlantic Forest Bird Assemblages through Nested Species Loss. AB - The increasing number of quantitative assessments of homogenization using citizen science data is particularly important in the Neotropics, given its high biodiversity and ecological peculiarity, and whose communities may react differently to landscape changes. We looked for evidence of taxonomic homogenization in terrestrial birds by investigating patterns of beta diversity along a gradient of human-altered landscapes (HAL), trying to identify species associated with this process. We analyzed bird data from 87 sites sampled in a citizen science program in the south Brazilian Atlantic Forest. Regional-scale taxonomic homogenization was assessed by comparing beta diversity among sites in different HALs (natural, rural or urban landscapes) accounting for variation derived from geographical distance and zoogeographical affinities by georeferencing sites and determining their position in a phytogeographical domain. Beta diversity was calculated by multivariate dispersion and by testing compositional changes due to turnover and nestedness among HALs and phytogeographical domains. Finally, we assessed which species were typical for each group using indicator species analysis. Bird homogenization was indicated by decreases in beta diversity following landscape changes. Beta diversity of rural sites was roughly half that of natural habitats, while urban sites held less than 10% of the natural areas' beta diversity. Species composition analysis revealed that the turnover component was important in differentiating sites depending on HAL and phytogeography; the nestedness component was important among HALs, where directional species loss is maintained even considering effects of sampling effort. A similar result was obtained among phytogeographical domains, indicating nested-pattern dissimilarity among compositions of overlapping communities. As expected, a few native generalists and non-native urban specialists were characteristic of rural and urban sites. We generated strong evidence that taxonomic homogenization occurs in the south Brazilian Atlantic Forest as a result of a directional and nested species loss, with the resultant assemblages composed of few disturbance-tolerant birds. PMID- 26840956 TI - Whisker Deprivation Drives Two Phases of Inhibitory Synapse Weakening in Layer 4 of Rat Somatosensory Cortex. AB - Inhibitory synapse development in sensory neocortex is experience-dependent, with sustained sensory deprivation yielding fewer and weaker inhibitory synapses. Whether this represents arrest of synapse maturation, or a more complex set of processes, is unclear. To test this, we measured the dynamics of inhibitory synapse development in layer 4 of rat somatosensory cortex (S1) during continuous whisker deprivation from postnatal day 7, and in age-matched controls. In deprived columns, spontaneous miniature inhibitory postsynaptic currents (mIPSCs) and evoked IPSCs developed normally until P15, when IPSC amplitude transiently decreased, recovering by P16 despite ongoing deprivation. IPSCs remained normal until P22, when a second, sustained phase of weakening began. Delaying deprivation onset by 5 days prevented the P15 weakening. Both early and late phase weakening involved measurable reduction in IPSC amplitude relative to prior time points. Thus, deprivation appears to drive two distinct phases of active IPSC weakening, rather than simple arrest of synapse maturation. PMID- 26840959 TI - Multidisciplinary Clinical Case Study. PMID- 26840960 TI - A Multidisciplinary Approach to Castleman Disease of the Neck. AB - Castleman disease (CD) is a rare lymphoproliferative disorder that occurs in adults and rarely in the pediatric population. The disease is characterized by slowly enlarging masses that can form anywhere within the lymphatic system. It is an uncommon cause of a neck mass in both children and adults that presents insidiously and nonspecifically. A 21-year-old woman was referred to the otolaryngology service because of an asymptomatic neck mass found incidentally on computed tomographic imaging 15 months earlier. On repeat imaging, the lesion was characterized as a homogenously enhancing soft tissue mass and appeared stable in size compared with previous studies. Given the nondiagnostic radiologic features, tissue sampling was pursued, first using fine-needle aspiration and ultimately excisional biopsy. The excision revealed histopathology consistent with unicentric, hyaline-vascular CD. Excision is the gold standard for treatment of this variant of CD. The patient was referred to the hematology/oncology service but was subsequently lost to follow-up. This case illustrates a rare cause of a neck mass in a young adult and exemplifies the extremely broad differential in this setting. In addition, it highlights the importance of a systematic and thorough approach to diagnosing neck masses in children and adults. PMID- 26840958 TI - Inhibition of Cellular Adhesion by Immunological Targeting of Osteopontin Neoepitopes Generated through Matrix Metalloproteinase and Thrombin Cleavage. AB - Osteopontin (OPN), a secreted protein involved in inflammatory processes and cancer, induces cell adhesion, migration, and activation of inflammatory pathways in various cell types. Cells bind OPN via integrins at a canonical RGD region in the full length form as well as to a contiguous cryptic site that some have shown is unmasked upon thrombin or matrix metalloproteinase cleavage. Thus, the adhesive capacity of osteopontin is enhanced by proteolytic cleavage that may occur in inflammatory conditions such as obesity, atherosclerosis, rheumatoid arthritis, tumor growth and metastasis. Our aim was to inhibit cellular adhesion to recombinant truncated proteins that correspond to the N-terminal cleavage products of thrombin- or matrix metalloproteinase-cleaved OPN in vitro. We specifically targeted the cryptic integrin binding site with monoclonal antibodies and antisera induced by peptide immunization of mice. HEK 293 cells adhered markedly stronger to truncated OPN proteins than to full length OPN. Without affecting cell binding to the full length form, the raised monoclonal antibodies specifically impeded cellular adhesion to the OPN fragments. Moreover, we show that the peptides used for immunization were able to induce antisera, which impeded adhesion either to all OPN forms, including the full-length form, or selectively to the corresponding truncated recombinant proteins. In conclusion, we developed immunological tools to selectively target functional properties of protease-cleaved OPN forms, which could find applications in treatment and prevention of various inflammatory diseases and cancers. PMID- 26840961 TI - Hepatic Dysfunction in Patients Receiving Intravenous Amiodarone. AB - OBJECTIVES: Amiodarone is a commonly used antiarrhythmic drug. Hepatotoxicity following chronic oral administration occurs in 1% to 3% of patients. Hepatotoxicity following intravenous (IV) administration is infrequent but may be associated with dramatic increases in serum transaminases. We describe the incidence of liver toxicity among patients receiving IV amiodarone during a 5 year period. METHODS: This was a single-center retrospective review of patients receiving IV amiodarone for any cause. The outcome measures were development of elevated serum transaminases and the relation of transaminitis to all-cause 30 day mortality. RESULTS: A total of 1510 patients received amiodarone intravenously between 2005 and 2011; 77 (5%) developed elevated liver enzymes. Enzyme elevation was divided into mild (100-300 IU/L), moderate (300-1000 IU/L), and severe (>1000 IU/L). The median alanine aminotransferase was 189 (37-10,006) IU/L and aspartate aminotransferase was 253 (84-12,005) IU/L. The 30-day mortality among those with transaminitis was 22%; however, no patient died of amiodarone-related liver disease. CONCLUSIONS: Amiodarone can cause severe elevation in liver enzymes. The incidence of severe transaminitis is low; deaths following IV amiodarone are rarely caused by drug-induced liver failure. PMID- 26840962 TI - 10 Practice Recommendations in Adult Vaccination Administration. AB - Although the provision of immunoprophylaxis to children has become routine in the practice of pediatric preventive care, the same is not true in adult primary care. Contributing to this problem is a lack of knowledge among providers of adult preventive care. This review aimed to bolster providers' understanding of adult vaccinations by highlighting changes in vaccination recommendations and addressing common knowledge gaps. This is not a comprehensive list of vaccination recommendations, but rather the "top 10" common misconceptions, advancements, and updates we have found in our reading of the vaccination literature and in our own experience in a training institution. PMID- 26840964 TI - Iatrogenic Subclinical Hyperthyroidism Does Not Promote Weight Loss. AB - OBJECTIVES: Among patients who have undergone total thyroidectomy, do those with thyroid cancer being kept iatrogenically subclinical hyperthyroid (SCH) differ from euthyroid patients in long-term weight change? METHODS: In a retrospective study, medical records identified 291 patients who had undergone a thyroidectomy for differentiated thyroid cancer or benign thyroid disease. Weight, thyroid stimulating hormone, and levothyroxine dose were measured presurgery and 1, 2, and 3 years postsurgery. RESULTS: Of 291 patients, 147 were in the SCH group and 144 were in the euthyroid group. At all 3 years both groups gained weight from baseline, but the two groups did not differ in weight change from baseline at any time period: year 1 (SCH mean 0.4% +/- 6.2% weight gain vs euthyroid group mean 2.2% +/- 6.6% weight gain; P = 0.12), year 2 (SCH mean 1.1% +/- 9.1% weight gain vs euthyroid mean 2.9% +/- 7.8% weight gain; P = 0.22), and year 3 (SCH mean 2.6% +/- 9.2% weight gain vs euthyroid mean 3.1% +/- 11.1% weight gain; P = 0.49). CONCLUSIONS: Among total thyroidectomy patients, weight change did not differ between SCH patients and euthyroid patients at years 1 through 3. As such, the use of levothyroxine to induce SCH did not lead to long-term weight change when compared with euthyroid patients. PMID- 26840963 TI - Does Alkaline Colonic pH Predispose to Clostridium difficile Infection? AB - OBJECTIVES: Clostridium difficile caused nearly 500,000 infections and was associated with approximately 29,000 deaths in 2011, according to data from the Centers for Disease Control and Prevention. C. difficile is a bacterium that causes diarrhea and, often, severe illness in healthcare facilities, as well as the community. Our objective was to determine whether alkaline colonic pH predisposes to colonization and infection with C. difficile. METHODS: A total of 228 patients with diarrhea and/or abdominal pain, leukocytosis, and fever were included. Stool pH was measured, and C. difficile antigen and toxin in stool were detected. RESULTS: Of 228 patients, 30 (13.2%) tested positive for C. difficile (antigen+/toxin+) and 171 (75%) were C. difficile negative (antigen-/toxin-). Of 171 patients who tested negative, 93 (54.4%) had stool pH >7.0 and 78 (45.6%) had pH <=7.0. Among the 30 patients who tested positive, 26 (86.7%) had stool pH >7.0 (P = 0.002). Among the 27 colonized patients (antigen+/toxin-), 12 (44.4%) had stool pH >7.0 (P = 0.34). For all patients with stool pH <=7.0, 96% tested negative for C. difficile infection (P = 0.002). CONCLUSIONS: A strong association between C. difficile infection and alkaline stool pH was found. PMID- 26840965 TI - Senior Medical Student Mock Interview Program in Pediatrics. AB - OBJECTIVES: Residency interviews play an integral part in medical residency placement. We aimed to develop and evaluate a mock interview program for fourth year medical students interested in a pediatric specialty. METHODS: A mock interview program for fourth-year medical students interested in pediatrics was developed and implemented. Preinterview quantitative data and postinterview qualitative data were collected. Fifty-nine students completed the program across three consecutive academic years. Preinterview surveys were completed regarding comfort and confidence levels specific to aspects of the interview process. Descriptive analyses were used. In addition, a focus group was held with nine of the participating students to obtain qualitative data via a paper blog process. Themes in student responses were identified through constant comparative analysis. RESULTS: Before the mock interview, students were most uncomfortable with introductory and closing remarks and their confidence levels varied by topic. A thematic analysis of focus group data identified five themes (preparation, stress reduction, interview process familiarity, confidence of skills, and receiving feedback) for which the mock interviews were most helpful. CONCLUSIONS: Implementation of a mock interview program was feasible and acceptable for senior medical students and may improve comfort and confidence levels in the residency interview process. Further longitudinal research is needed. PMID- 26840966 TI - Commentary on "Senior Medical Student Mock Interview Program in Pediatrics". PMID- 26840967 TI - Ambulatory Morning Report: A Case-Based Method of Teaching EBM Through Experiential Learning. AB - OBJECTIVES: Evidence-based medicine (EBM) skills are important to daily practice, but residents generally feel unskilled incorporating EBM into practice. The Kolb experiential learning theory, as applied to curricular planning, offers a unique methodology to help learners build an EBM skill set based on clinical experiences. We sought to blend the learner-centered, case-based merits of the morning report with an experientially based EBM curriculum. We describe and evaluate a patient-centered ambulatory morning report combining the User's Guides to the Medical Literature approach to EBM and experiential learning theory in the internal medicine department at Baystate Medical Center. METHODS: The Kolb experiential learning theory postulates that experience transforms knowledge; within that premise we designed a curriculum to build EBM skills incorporating residents' patient encounters. By developing structured clinical questions based on recent clinical problems, residents activate prior knowledge. Residents acquire new knowledge through selection and evaluation of an article that addresses the structured clinical questions. Residents then apply and use new knowledge in future patient encounters. RESULTS: To assess the curriculum, we designed an 18-question EBM test, which addressed applied knowledge and EBM skills based on the User's Guides approach. Of the 66 residents who could participate in the curriculum, 61 (92%) completed the test. There was a modest improvement in EBM knowledge, primarily during the first year of training. CONCLUSIONS: Our experiential curriculum teaches EBM skills essential to clinical practice. The curriculum differs from traditional EBM curricula in that ours blends experiential learning with an EBM skill set; learners use new knowledge in real time. PMID- 26840968 TI - Patient Satisfaction with Bedside Teaching Rounds Compared with Nonbedside Rounds. AB - OBJECTIVES: Many barriers have been cited in reference to why bedside teaching rounds have decreased in frequency during graduate medical education. One perceived barrier to the use of bedside teaching rounds is a fear of it causing patient discomfort or dissatisfaction. The objective of this study was to compare patient perception of bedside versus nonbedside teaching rounds. METHODS: Study participants were adults admitted to a family medicine inpatient team at a large university teaching hospital. Upon admission, participants were randomized to receive bedside or nonbedside teaching rounds conducted by a team consisting of medical students, family medicine residents, and one attending physician. Each participant completed a questionnaire administered on the day of discharge assessing patients' perception of their involvement in medical decision making, trust in the medical team, satisfaction with care, and provider compassion. Statistical analysis was performed to examine any differences between the two groups. RESULTS: The vast majority of the sample indicated that they knew what they were being treated for in the hospital (n = 105, 98%), reported the medical team spent an adequate amount of time with them (n = 100, 94%), and reported the medical team explained the diagnosis and care in easy-to-understand terms (n = 101, 94%). On 1- to 5-point scales, participants reported that the medical team involved them in making decisions (4.62, standard deviation [SD] 0.72), they trusted the medical team (4.91, SD 0.32), they were satisfied with their care (4.85, SD 0.38), and their medical team was compassionate toward them (4.84, SD 0.44). Overall levels of satisfaction were positive on all of the measures, with no statistical significance between the two groups regarding measures of involvement in medical decision making, trust in the medical team, and satisfaction with care. Interestingly, subjects perceived level of compassion of their medical team to be significantly higher with a bedside teaching approach compared with a nonbedside approach. CONCLUSIONS: Despite concerns that bedside teaching rounds may lead to patient discomfort, this study found no evidence supporting this perception. In fact, patients may perceive a medical team that engages in bedside teaching rounds as being more compassionate providers, supporting a patient-centered argument that teaching rounds should return to the bedside. PMID- 26840969 TI - Commentary on "Patient Satisfaction with Bedside Teaching Rounds Compared with Nonbedside Rounds". PMID- 26840971 TI - Newborn Congenital Malformations Associated With Prenatal Exposure to Drugs in Kentucky, 2009-2013. AB - OBJECTIVES: This study examined associations between prenatal drug exposures and congenital organ system malformation diagnoses in newborns (at birth) and infants (hospitalizations after birth up to 30 days of age) in Kentucky. METHODS: Data were obtained from Kentucky inpatient hospitalization records for newborns and for infants from 2009 to 2013. Prenatal drug exposures and congenital anomalies were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes for prenatal drug exposures (760.70-760.79; 304; 779.5) and congenital anomalies (740-759). Descriptive analyses and logistic regression were performed. RESULTS: Neonatal abstinence syndrome was the most frequent prenatal drug exposure-related diagnosis in newborns (1%). Cardiac and circulatory malformation diagnoses were significantly elevated in newborns prenatally exposed to drugs compared with cardiac and circulatory malformation diagnoses in newborns with no prenatal drug exposures (P < 0.0001); genital and urinary anomalies also were significantly elevated among newborns with prenatal drug exposures (P < 0.05). Newborns and infants diagnosed as having congenital malformations who were prenatally exposed to drugs had significantly extended hospitalization stays and higher total hospitalization charges compared with newborns and infants diagnosed as having congenital malformations who were not prenatally exposed to drugs (P < 0.0001). CONCLUSIONS: Further research is needed to identify specific risk factors (eg, drug classes, tobacco) and toxicities (eg, intake amount, frequency of intake, drug metabolism) associated with congenital malformation diagnoses following prenatal exposure to drugs. PMID- 26840970 TI - Changes in Nonosteoporotic Bone Density and Subsequent Fractures in Women. AB - OBJECTIVES: Osteopenia is considerably more common than osteoporosis and accounts for most of the fracture burden in women older than 50 years. It is uncertain when to initiate treatment in osteopenia. We sought to determine in women with osteopenia what effect transitioning to lower categories had on subsequent fracturing. METHODS: We surveyed 1150 women from office-based practices who had initial normal or osteopenic bone mineral densities (BMDs) and who were retested after 5.75 years. We classified categories related to baseline T scores as follows: normal (>-1.0), mild osteopenia (-1.0 to -1.49), moderate osteopenia ( 1.5 to -1.99), and severe osteopenia (-2.0 to -2.49). We determined during a 9.6 year follow-up period the fracture occurrence in those who maintained their initial category status or transitioned into lower categories. RESULTS: Transitioning to lower categories was not significantly different among baseline osteopenic categories but significantly more than normal baseline BMDs. Total fractures, individuals fracturing, and major fractures were significantly more, with baseline T scores of <=-1.5 (<0.001). Although only 10.2% transitioned to osteoporosis, 90.5% of these transitions occurred with baseline T scores <=-1.5 and accounted for significantly more fractures than baseline T scores of >-1.5. CONCLUSIONS: Most subsequent fractures and transitions to osteoporosis occurred with baseline T scores <=-1.5. Clinical risk factors need to be used to determine at what T score threshold treatment would be cost effective. PMID- 26840973 TI - Erratum: Pediatric Dyslipidemia: Recommendations for Clinical Management: Erratum. PMID- 26840972 TI - Cardiovascular Disease Risk Factors in Hispanic Adolescents in South Texas. AB - OBJECTIVES: Despite a national crisis of increased prevalence of obesity and type 2 diabetes mellitus in adolescents, especially among Hispanics, there is a paucity of data on health indicators among farmworker adolescents and their peers. The main aim of this study was to estimate the prevalence of cardiovascular disease risk factors in a population of Hispanic adolescent students in south Texas. The study also aimed to compare the prevalence of these risk factors between students enrolled in the Migrant Education Program (MEP) and other students, and between boys and girls. METHODS: In partnership with the Weslaco (Texas) Independent School District and the Migrant Education Department, a cohort study was conducted from 2007 to 2010 to estimate the prevalence of overall obesity (body mass index >=85th percentile for age and sex), abdominal obesity (waist circumference >=75th percentile for age, sex, and ethnicity), acanthosis nigricans (AN), and high blood pressure (HBP; >=90th percentile for age, height, and sex or systolic/diastolic BP >=120/80 mm Hg) among MEP students compared with other students from two south Texas high schools. Multilevel logistic regression was used to assess the relation between sex and our main outcomes of interest while accounting for within-school nesting of participants. RESULTS: Among 628 sampled students, 508 (80.9%) completed the consent procedure and participated in the study. Of these, 257 were MEP students and 251 were non MEP peers. Approximately 96.7% of participants were Hispanic and 50.0% were boys. Analyses of data across the years comparing MEP students and non-MEP students show an average prevalence of 44.8% versus 47.7% for overall obesity, 43.2% versus 43.7% for abdominal obesity, 24.7% versus 24.7% for AN, and 29.2% versus 32.8% for HBP. Across recruitment and follow-up years, the prevalence of overall obesity, abdominal obesity, and HBP was 1.3 to 1.5, 1.2 to 1.8, and 2.9 to 4.6 times higher in boys than in girls, respectively. In contrast, the prevalence of AN varied little by sex. CONCLUSIONS: The high prevalence of cardiovascular risk factors in both groups suggests a compelling need for comprehensive, culturally targeted interventions to prevent future cardiovascular diseases in these high risk Hispanic adolescents, especially among boys. There were not, however, substantial differences between MEP students and other students. These findings also support the feasibility of conducting future epidemiologic studies among adolescent farmworkers and their families, as well as culturally appropriate school or community-based interventions. PMID- 26840974 TI - The Formation of Stromules In Vitro from Chloroplasts Isolated from Nicotiana benthamiana. AB - Stromules are stroma-containing tubules that have been observed to emanate from the main plastidic body in vivo. These structures have been shown to require cytoskeletal components for movement. Though numerous studies have shown a close association with the endoplasmic reticulum, nucleus, mitochondria, and other plastids, the mechanism of formation and their overall function remain unknown. A limiting factor in studying these structures has been the lack of a reconstituted system for in vitro stromule formation. In this study, stromule formation was induced in vitro by adding a plant extract fraction that is greater than 100 kDa to a population of isolated chloroplasts. Kinetic measurements show that stromule formation occurs within ~10 seconds after the addition of the plant extract fraction. Heat inactivation and apyrase treatment reveal that the stromule stimulating compound found in the extract fraction is a protein or protein complex 100 kDa or greater. The formation of the stromules in vitro with isolated chloroplasts and a concentrated fraction of cell extract opens an avenue for the biochemical dissection of this process that has heretofore been studied only in vivo. PMID- 26840976 TI - Correction: Localisation of Nursery Areas Based on Comparative Analyses of the Horizontal and Vertical Distribution Patterns of Juvenile Baltic Cod (Gadus morhua). PMID- 26840975 TI - Effect of donor cardiac arrest and arrest duration on outcomes of lung transplantation. AB - BACKGROUND: Limited data are available about lung transplantation (LTx) from donors suffering cardiac arrest (CA) prior to actual donation. METHODS: A retrospective analysis of LTx performed between January 2007 and September 2012 was done with the focus on CA in donors. The recipients were grouped depending on the history of donor CA and CA duration (downtime) as: No cardiac arrest ("NoCA"), CA downtime less than 20 min ("CA < 20"), and CA downtime equal to or more than 20 min ("CA > 20"). Early and mid-term outcomes after LTx were compared among the three groups. RESULTS: A total of 237 LTx were performed during the study period. One hundred eighty-eight patients received organs from "NoCA" donors, 25 from "CA < 20" donors, and 24 patients from "CA > 20" donors. There was a trend toward better overall cumulative survival in both CA groups (log rank p = 0.076) whereas the survival in the "CA > 20" group was significantly better than in the "NoCA" group in the subgroup analysis (log rank p = 0.045). Freedom from bronchiolitis obliterans syndrome (BOS) also increased with increase in CA duration, although it did not reach statistical significance. CONCLUSIONS: Transplantation of lungs from donors with a history of CA is safe and feasible. Longer duration of cardiac arrest may improve the outcomes after the LTx in terms of survival and freedom from BOS. PMID- 26840978 TI - Rhodium-Catalyzed Cyclization of 2-Ethynylanilines in the Presence of Isocyanates: Approach toward Indole-3-carboxamides. AB - Catalytic synthesis of indole-3-carboxamides from 2-ethynylanilines and isocyanates was achieved in the presence of a rhodium catalyst through a tandem type, cyclization-addition sequence. This tandem-type process can be performed under mild reaction conditions, affording 2,3-disubstituted indoles in a one-pot manner generally in good to excellent yields. The broad substrate scope and good functional group compatibility make the method highly efficient and widely applicable, providing a facile and entirely novel route toward variously substituted indole-3-carboxamides. PMID- 26840977 TI - Single Nucleotide Polymorphisms in IL17A and IL6 Are Associated with Decreased Risk for Pulmonary Tuberculosis in Southern Brazilian Population. AB - In Mycobacterium tuberculosis (MTB) infection, the complex interaction of host immune system and the mycobacteria is associated with levels of cytokines production that play a major role in determining the outcome of the disease. Several single-nucleotide polymorphisms (SNPs) in cytokine genes have been associated with tuberculosis (TB) outcome. The aim of this study was to evaluate the association between previously reported SNPs IL2-330 T>G (rs2069762); IL4-590 C>T (rs2243250); IL6-174 G>C (rs1800795); IL10-592 A>C (rs1800872); IL10-1082 G>A (rs1800896); IL17A -692 C>T (rs8193036); IL17A -197 G>A (rs2275913); TNF -238 G>A (rs361525); TNF -308 G>A (rs1800629) and IFNG +874 T>A (rs2430561) and pulmonary TB (PTB) susceptibility. We conducted a case-control study in individuals from Southern Brazil who were recruited between February 2012 and October 2013 in a high incidence TB city. We performed a multiplex genotyping assay in 191 patients with PTB and 175 healthy subjects. Our results suggest a decreased risk for PTB development associated with the IL17A -197A allele (OR = 0.29; p = 0.04), AA genotype (OR = 0.12; p = 0.04) and A carrier (AG/AA) (OR = 0.29; p = 0.004) and IL6 -174C carrier (CC/CG) (OR = 0.46; p = 0.04). We could not properly analyze IL17A -692 C>T (rs8193036) and IFNG +874T>A due to genotypic inconsistencies and found no evidence of association for the IL2, IL4, IL10 and TNF polymorphisms and PTB. In conclusion, our results show a protective effect of IL17 and IL6 polymorphisms on PTB outcome in Southern Brazilian population. PMID- 26840979 TI - Evaluation of Metal-Organic Frameworks and Porous Polymer Networks for CO2 Capture Applications. AB - This manuscript presents experimental data for 20 adsorption materials (metal organic frameworks, porous polymer networks, and Zeolite-5A), including CO2 and N2 isotherms and heat capacities. With input from only experimental data, working capacities per energy for each material were calculated. Furthermore, by running seven different carbon-capture scenarios in which the initial flue-gas composition and process temperature was systematically changed, we present a range of performances for each material and quantify how sensitive each is to these varying parameters. The presented calculations provide researchers with a tool to investigate promising carbon-capture materials more easily and completely. PMID- 26840981 TI - Effects of nitrogen dopants on the atomic step kinetics and electronic structures of O-polar ZnO. AB - Oxygen-polar ZnO films are grown in step flow mode by molecular beam epitaxy. Driven by the step flow anisotropy, the growth leads to the occurrence of specific hexagonal pits in the surface. The specific pits are formed by interlacing steps of the {1014} facets, thus quenching the macroscopic dipole moment along the c-axis and satisfying the stabilization principles. Nitrogen (N) doping trials are then performed on the basis of the stable surface. In doping, growth remains in step flow mode but the step flow anisotropy vanishes, resulting in an obvious change of the surface morphology. Besides, a distinct acceptor state appears by in situ scanning tunneling spectroscopy analysis. First principles calculations reveal that N readily substitutes for step-edge Zn and acts as NO2 adsorbed at the step edge. Desorption of the NO2 facilitates the formation of NO-VZn shallow acceptor complexes, which contributes to the appearance of the acceptor state. According to the peculiarities of N dopants on the O-polar surface, vicinal O-polar substrates (e.g., {1014} substrate) are promising in ZnO : N due to the easily achieved step flow growth and high density of step edges for N incorporation. PMID- 26840982 TI - HPLC-MS with Glass Chips Featuring Monolithically Integrated Electrospray Emitters of Different Geometries. AB - We present and evaluate an approach for coupling liquid chromatography in glass chips with mass spectrometry via fully integrated electrospray emitters. We developed an instrumental platform which allows a robust and reproducible operation of high performance chip chromatography coupled to mass spectrometry. A comparison of differently shaped emitters, from flat over edged to pulled geometries, revealed that all types performed equally well for typical nano-HPLC flow rates. At very low flow rates below 50 nL.min(-1) very sharp, pulled nanospray emitters turned out to be mandatory for the generation of a stable electrospray. PMID- 26840980 TI - Loss of Endothelial Barrier in Marfan Mice (mgR/mgR) Results in Severe Inflammation after Adenoviral Gene Therapy. AB - OBJECTIVES: Marfan syndrome is an autosomal dominant inherited disorder of connective tissue. The vascular complications of Marfan syndrome have the biggest impact on life expectancy. The aorta of Marfan patients reveals degradation of elastin layers caused by increased proteolytic activity of matrix metalloproteinases (MMPs). In this study we performed adenoviral gene transfer of human tissue inhibitor of matrix metalloproteinases-1 (hTIMP-1) in aortic grafts of fibrillin-1 deficient Marfan mice (mgR/mgR) in order to reduce elastolysis. METHODS: We performed heterotopic infrarenal transplantation of the thoracic aorta in female mice (n = 7 per group). Before implantation, mgR/mgR and wild type aortas (WT, C57BL/6) were transduced ex vivo with an adenoviral vector coding for human TIMP-1 (Ad.hTIMP-1) or beta-galactosidase (Ad.beta-Gal). As control mgR/mgR and wild-type aortas received no gene therapy. Thirty days after surgery, overexpression of the transgene was assessed by immunohistochemistry (IHC) and collagen in situ zymography. Histologic staining was performed to investigate inflammation, the neointimal index (NI), and elastin breaks. Endothelial barrier function of native not virus-exposed aortas was evaluated by perfusion of fluorescent albumin and examinations of virus-exposed tissue were performed by transmission electron microscopy (TEM). RESULTS: IHC and ISZ revealed sufficient expression of the transgene. Severe cellular inflammation and intima hyperplasia were seen only in adenovirus treated mgR/mgR aortas (Ad.beta Gal, Ad.hTIMP-1 NI: 0.23; 0.43), but not in native and Ad.hTIMP-1 treated WT (NI: 0.01; 0.00). Compared to native mgR/mgR and Ad.hTIMP-1 treated WT aorta, the NI is highly significant greater in Ad.hTIMP-1 transduced mgR/mgR aorta (p = 0.001; p = 0.001). As expected, untreated Marfan grafts showed significant more elastolysis compared to WT (p = 0.001). However, elastolysis in Marfan aortas was not reduced by adenoviral overexpression of hTIMP-1 (compared to untreated Marfan aorta: Ad.hTIMP-1 p = 0.902; control Ad.beta-Gal. p = 0.165). The virus-untreated and not transplanted mgR/mgR aorta revealed a significant increase of albumin diffusion through the endothelial barrier (p = 0.037). TEM analysis of adenovirus exposed mgR/mgR aortas displayed disruption of the basement membrane and basolateral space. CONCLUSIONS: Murine Marfan aortic grafts developed severe inflammation after adenoviral contact. We demonstrated that fibrillin-1 deficiency is associated with relevant dysfunction of the endothelial barrier that enables adenovirus to induce vessel-harming inflammation. Endothelial dysfunction may play a pivotal role in the development of the vascular phenotype of Marfan syndrome. PMID- 26840983 TI - Ophthalmological Assessment of OCT and Electrophysiological Changes in Migraine Patients. AB - BACKGROUND: A cross-sectional study to investigate the morphological and functional changes of the visual pathway taking place in patients with migraine. METHODS: Fifteen patients (14 female, 1 male) diagnosed with migraine with aura and 23 patients (21 female, 2 male) diagnosed with migraine without aura were compared with 20 healthy volunteers (18 female, 2 male). All the participants underwent optical coherence tomography scan, electroretinogram (ERG), visual evoked potentials, and multifocal electroretinogram (mf-ERG) recording. RESULTS: Assessing ERG recordings, no significant differences in mean N1-P1 amplitudes were measured among the groups. The mean visual evoked potentials N80-P100 amplitudes were not significantly different among the three groups (one way analysis of variance: P = 0.075, F = 2.718). No significant difference was found in P100 latency times among groups. The mean retinal response density of mf-ERG in ring 1 was higher in healthy individuals compared with migraineurs, with statistical significance (Kruskal-Wallis analysis of variance and Dunn multiple comparisons test; P < 0.001, mean rank difference = -24.857 and P < 0.001, mean rank difference = -20.9, for migraine with aura-control and migraine without aura control comparisons, respectively). In migraine with aura subjects, retinal nerve fiber layer thickness in superior and inferior quadrants was significantly decreased compared with healthy individuals, whereas in migraine without aura group, only the superior quadrant was significantly thinner compared with the control group. CONCLUSIONS: Retinal response density in mfERG of all migraineurs was significantly lessened compared with healthy individuals. There was no significant difference in visual evoked potentials N80-P100 amplitudes or P100 latencies among the groups. Moreover, retinal nerve fiber layer thinning observed in patients with migraine compared with control subjects, appeared statistically significant in some quadrants. The authors may be able to defend the retinal blood flow decrease theory in migraine. The results also indicate that several levels of the visual pathway seem to be affected in migraineurs. PMID- 26840984 TI - Principles of Stereotactic Electroencephalography in Epilepsy Surgery. AB - Stereotactic electroencephalography is a method for the invasive study for the human epileptic brain as a prelude to epilepsy surgery. The discipline of stereotactic electroencephalography is underpinned by an anatomo-electro-clinical analysis of epileptic seizures of focal origin and goes beyond simple stereotactic placement of depth electrodes. Stringent analysis of semiological and electrophysiological features is coupled with an understanding of this information in 3D anatomical space. Stereotactic electroencephalography offers significant advantages over subdural grid implantations, allowing pinpoint accuracy access to sulcal areas and deep brain structures, such as the insula, cingulate, basal and mesial brain regions, while associated with lower complication rates. Recent times have seen an exponential growth in stereotactic electroencephalography interest, driven in part by increasing complexity of typical epilepsy surgery patients in epilepsy surgery centers. Such patients are much more likely to be magnetic resonance imaging negative, or reoperations, or to have multifocal or widespread areas of cortical abnormalities. Herein, we discuss the advantages of stereotactic electroencephalography, principles of patient selection, implantation, and interpretation. PMID- 26840985 TI - Microbial enzyme and biomass responses: Deciphering the effects of earthworms and seasonal variation on treating excess sludge. AB - This paper reports on a seasonal pattern comparison of microbial enzymatic activities and biomass responses based on a conventional biofilter (BF, without earthworm) and a vermifilter (VF, with earthworm, Eisenia fetida) for excess sludge treatment. The volatile suspended solids (VSS) reduction, viable cell number and enzyme activities were assayed to probe what made the VF operate stably. The results indicated that the earthworm activities can polish the VSS reduction with 27.17% more than the BF. Though the VF had a lower level in the viable cell number compared with the BF, the earthworm strongly improved the microbial enzymatic activities such as INT-dehydrogenase, protease, beta glucosidase and amylase, which can explain the excellent performance of VSS reduction. The correlation analysis documented that the VSS reduction was positively correlated with microbial enzyme activities. More importantly, the earthworm enabled the VF to avoid the detrimental influence of temperature, which guaranteed a stable performance during seasonal variations. PMID- 26840986 TI - Intraretinal variability and specialization of cones in Japanese anchovy (Engraulis japonicus, Engraulidae). AB - The retina of anchovies is characterized by an unusual arrangement and ultrastructure of cones. In the retina of Japanese anchovies, Engraulis japonicus, three types of cones are distributed into rows. The nasal, central, temporal, and ventro-temporal regions of the retina were occupied exclusively by the long and short cones. Triple cones, made up of two lateral components and one smaller central component, were found only in the dorsal and ventro-nasal retinal regions. In the outer segments of all short and long cones from the ventro temporal region, the lamellae were oriented along the cell axis and were perpendicular to the lamellae in the long cones, providing a morphological basis for the detection of polarization. This lamellar orientation is unique to all vertebrates. The cones were examined with respect to regional differentiation in their size and spectral properties via light microscopy, transmission electron microscopy, and microspectrophotometry. Various dimensions of cones were measured in preparations of isolated cells. The cones from the ventro-temporal region had different dimensions than cones of the same type located in other retinal regions. Triple cones from the dorsal region were significantly larger than triple cones from the ventro-nasal region. The spectral absorbance of the lateral components of triple cones in the ventro-nasal retina was identical to the absorbance of all long and short cones from the ventro-temporal region. These are shifted to shorter wavelengths relative to the absorbance of the lateral components of the triple cones located in the dorsal retina. Thus, the retina of the Japanese anchovy shows some features of regional specialization common in other fishes that improves spatial resolution for the upwards and forwards visual axis and provides spectral tuning in downwelling light environment. That results from the differentiation of cone types by size and by different spectral sensitivity of various retinal areas. PMID- 26840987 TI - Fetal arrhythmogenic right ventricular cardiomyopathy with double mutations in TMEM43. AB - We herein describe a fetal case of arrhythmogenic right ventricular cardiomyopathy (ARVC) with double mutations in transmembrane protein 43 (TMEM43). RV aneurysm and ventricular arrhythmia were detected during the fetal period. After birth, electrocardiogram showed frequent premature ventricular contractions (PVC) of left bundle branch block morphology and epsilon waves in the right-sided chest leads. Echocardiography also indicated RV aneurysm with regionally decreased systolic function. PVC disappeared after treatment with amiodarone and mexiletin. Mutations in TMEM43, which was recently identified as the causative gene of ARVC type 5, were also confirmed in the present patient and in the patient's mother, and they were therefore diagnosed with ARVC. The present case confirms that symptoms of ARVC can emerge during the fetal period. Pediatricians need to keep in mind the possibility of ARVC when they encounter patients with RV aneurysm and arrhythmia. PMID- 26840988 TI - Motivational interviewing in paediatric residency. AB - BACKGROUND: Motivational interviewing (MI) is a collaborative, evidence-based, person-centred counselling style for addressing ambivalence about behaviour change. Despite its proven effectiveness, there is little formal instruction of MI in paediatric training programmes. METHODS: Second-year paediatric residents participated in a 4-hour MI workshop, followed by a 1-hour small group review course and hands-on supervision during their Adolescent Medicine rotation. After the MI workshop, and again after their refresher course, we assessed residents' attitudes and skill with written and online surveys, as well as with a modified Helpful Responses Questionnaire (HRQ). RESULTS: Results revealed a statistically significant improvement in residents' confidence in eliciting health behaviour change [t-score(59) = 3.76, p = 0.008]. HRQ scores for all three clinical scenarios improved significantly following the workshop (p < 0.000). Residents most valued the interactive components of the workshop and review course, particularly the practice exercises, videos/video vignettes, feedback and coaching. DISCUSSION: A standardised MI curriculum for paediatric residency training improved residents' confidence in eliciting health behaviour change and use of empathic, reflective language. The curriculum is both feasible and widely accepted by residents, with opportunities for residents to practise MI under supervision during resident training. In conclusion, providing a 4-hour MI workshop for paediatric residents, with reinforcement through a review course and clinical opportunities to practise MI under supervision, improved confidence in eliciting health behaviour change and the use of MI-consistent language. This innovative and time-sensitive effort could serve as a future model for MI training for paediatric residents. There is little formal instruction of MI in paediatric training programmes. PMID- 26840989 TI - Ultrafast electrokinetics. AB - The influence of a high electric field applied on both fluid flow and particle velocities is quantified at large Peclet numbers. The experiments involved simultaneous particle image velocimetry and flow rate measurements. These are conducted in polydimethylsiloxane channels with spherical nonconducting polystyrene particles and DI water as the background flow. The high electric field tests produced up to three orders of magnitude higher electrokinetic velocities than any previous reports. The maximum electroosmotic velocity and electrophoretic velocity measured were 3.55 and 2.3 m/s. Electrophoretic velocities are measured over the range of 100 V/cm < E < 250 000 V/cm. The results are separated according to the different nonlinear theoretical models, including low and high Peclet numbers, and weak and strong concentration polarization. They show good agreement with the models. Such fast velocities could be used for flow separation, mixing, transport, control, and manipulation of suspended particles as well as microthrust generation among other applications. PMID- 26840990 TI - Glucose-6-Phosphate Dehydrogenase Deficiency in Brazilian Children With Sickle Cell Anemia is not Associated With Clinical Ischemic Stroke or High-Risk Transcranial Doppler. AB - BACKGROUND: Stroke is a severe complication of sickle cell anemia (SCA). The role of glucose-6-phosphate dehydrogenase (G6PD) deficiency in the development of stroke in children with SCA is controversial. PROCEDURE: The aim of this study was to investigate the association of clinical ischemic stroke, high-risk transcranial Doppler measurements (TCD), and hematological features with molecular variants usually linked to G6PD deficiency or with the biochemical activity of G6PD in a cohort of 395 Brazilian children with SCA. G6PD activity was quantitatively determined using an enzymatic-colorimetric assay. G6PD mutations were determined by PCR-RFLP and sequencing. Clinical and hematological data were retrieved from the children's records. RESULTS: The prevalence of molecularly defined deficiency (hereafter, molecular deficiency) was 4.3% (95% confidence interval: 2.3-6.3%). The mean G6PD activity was 16.88 U/g hemoglobin (Hb) (standard error of the mean [SEM] 0.28) in the group without G6PD molecular deficiency and 8.43 (SEM 1.01) U/g Hb in the group with G6PD A(-) molecular deficiency. G6PD molecular deficiency was not associated with any hematological features. No effects of G6PD molecular deficiency on clinical ischemic stroke or high-risk TCD were detected. The mean G6PD activity was similar in children who had clinical ischemic stroke and in those without stroke. Similar results were obtained in analyses comparing children who had high-risk TCD and those without high-risk TCD. CONCLUSIONS: Our study demonstrated that G6PD molecular deficiency was not associated either with clinical ischemic stroke or high-risk TCD. Similarly, we found no associations between G6PD enzyme activity and stroke or high-risk TCD. Small sample size precludes definitive conclusions. PMID- 26840991 TI - Patients With Atypical Femur Fractures Have the Same Mortality as the Background Population--Drug-Channeling Bias, Bisphosphonate Effects, and Public Health Implications. PMID- 26840992 TI - Photo-Patternable ZnO Thin Films Based on Cross-Linked Zinc Acrylate for Organic/Inorganic Hybrid Complementary Inverters. AB - Complementary inverters consisting of p-type organic and n-type metal oxide semiconductors have received considerable attention as key elements for realizing low-cost and large-area future electronics. Solution-processed ZnO thin-film transistors (TFTs) have great potential for use in hybrid complementary inverters as n-type load transistors because of the low cost of their fabrication process and natural abundance of active materials. The integration of a single ZnO TFT into an inverter requires the development of a simple patterning method as an alternative to conventional time-consuming and complicated photolithography techniques. In this study, we used a photocurable polymer precursor, zinc acrylate (or zinc diacrylate, ZDA), to conveniently fabricate photopatternable ZnO thin films for use as the active layers of n-type ZnO TFTs. UV-irradiated ZDA thin films became insoluble in developing solvent as the acrylate moiety photo cross-linked; therefore, we were able to successfully photopattern solution processed ZDA thin films using UV light. We studied the effects of addition of a tiny amount of indium dopant on the transistor characteristics of the photopatterned ZnO thin films and demonstrated low-voltage operation of the ZnO TFTs within +/-3 V by utilizing Al2O3/TiO2 laminate thin films or ion-gels as gate dielectrics. By combining the ZnO TFTs with p-type pentacene TFTs, we successfully fabricated organic/inorganic hybrid complementary inverters using solution-processed and photopatterned ZnO TFTs. PMID- 26840993 TI - Determinants of National Guard Mental Health Service Utilization in VA versus Non VA Settings. AB - OBJECTIVE: To determine associations between need, enabling, and predisposing factors with mental health service use among National Guard soldiers in the first year following a combat deployment to Iraq or Afghanistan. DATA SOURCES/STUDY SETTING: Primary data were collected between 2011 and 2013 from 1,426 Guard soldiers representing 36 units. STUDY DESIGN: Associations between Guard soldier factors and any mental health service use were assessed using multivariable logistic regression models in a cross-sectional study. Further analysis among service users (N = 405) assessed VA treatment versus treatment in other settings. PRINCIPAL FINDINGS: Fifty-six percent of Guard soldiers meeting cutoffs on symptom scales received mental health services with 81 percent of those reporting care from the VA. Mental health service use was associated with need (mental health screens and physical health) and residing in micropolitan communities. Among service users, predisposing factors (middle age range and female gender) and enabling factors (employment, income above $50,000, and private insurance) were associated with greater non-VA services use. CONCLUSION: Overall service use was strongly associated with need, whereas sector of use (non-VA vs. VA) was insignificantly associated with need but strongly associated with enabling factors. These findings have implications for the recent extension of veteran health coverage to non-VA providers. PMID- 26840995 TI - Preventing N- and O-formylation of proteins when incubated in concentrated formic acid. AB - Concentrated formic acid is among the most effective solvents for protein solubilization. Unfortunately, this acid also presents a risk of inducing chemical modifications thereby limiting its use in proteomics. Previous reports have supported the esterification of serine and threonine residues (O formylation) for peptides incubated in formic acid. However as shown here, exposure of histone H4 to 80% formic (1 h, 20(o) C) induces N-formylation of two independent lysine residues. Furthermore, incubating a mixture of Escherichia coli proteins in formic acid demonstrates a clear preference toward lysine modification over reactions at serine/threonine. N-formylation accounts for 84% of the 225 uniquely identified formylation sites. To prevent formylation, we provide a detailed investigation of reaction conditions (temperature, time, acid concentration) that define the parameters permitting the use of concentrated formic acid in a proteomics workflow for MS characterization. Proteins can be maintained in 80% formic acid for extended periods (24 h) without inducing modification, so long as the temperature is maintained at or below -20(o) C. PMID- 26840994 TI - The Usefulness of Intraoperative Cerebral C-Arm CT Angiogram for Implantation of Intracranial Depth Electrodes in Stereotactic Electroencephalography Procedure. AB - BACKGROUND: Stereotactic electroencephalography (SEEG) is an invasive diagnostic tool for localizing the epileptic zone in patients with medically refractory focal epilepsy. Despite technical and imaging advances in guiding the electrode placement, vascular injury is still one of its most serious complications. OBJECT: To investigate the usefulness of intraoperative cerebral C-arm CT angiogram (CCTA) in avoiding intracranial hemorrhagic complications during SEEG electrode implantation. METHODS: Trajectory data from 12 patients who underwent SEEG electrode implantation were studied in detail. This included an analysis of the implantation of 146 SEEG electrodes, which were guided by intraoperative CCTA, as well as the standard planning based on preoperative contrast-enhanced MRI. In addition, a prospective analysis of SEEG hemorrhagic complications using the studied methodology was performed in a total of 87 patients receiving 1,310 electrodes. RESULTS: There was no complication related to the CCTA itself. Intraoperative CCTA entailed modification of the original trajectory based on the preoperative MRI in 27 of 146 electrode implantations (18.5%). In 10 of them, a severe vascular complication was adverted by intraoperative CCTA. The safety of this new approach was also confirmed by the analysis of postinterventional CT, which revealed a symptomatic hematoma caused by 1 single electrode out of the 1,310 implanted. CONCLUSIONS: This study showed that intraoperative CCTA in addition to preoperative MRI is useful in guiding a safer SEEG electrode implantation. The combination of both imaging modalities essentially minimizes the risk of serious hemorrhagic complications. PMID- 26840996 TI - Externally Controlled Nanomachines on Mesoporous Silica Nanoparticles for Biomedical Applications. AB - Many machines (including nanomachines) consist of a solid support with moving parts that can undergo large amplitude motion to carry out specific tasks. In this Minireview, we will describe nanomachines that are supported on mesoporous silica nanoparticles that are typically 50-100 nanometers in diameter and have an array of open, readily accessible pores with an average width of a few nanometers. For triggering a large amplitude motion of the moving parts, we will focus primarily on external stimuli such as heat or light. As for the specific task the machines are carrying out, this Minireview will focus on the controlled release of pharmaceutically active agents in biomedical applications. We will discuss examples of how nanomachines can be used for remotely controlled cargo release and how existing machines that were originally designed to respond to internal physiological stimuli could be reconfigured to respond to external stimuli instead. PMID- 26840997 TI - Significant alterations of serum hormone levels in the spermatic vein plexus of patients with varicoceles. AB - The objective of this study was to evaluate the level of hormone variation between the peripheral blood and spermatic vein plexus in patients with varicoceles. A total of 23 patients diagnosed with varicoceles were enrolled in the study. All patients underwent a testicular artery-sparing microsurgical varicocelectomy. During the operation, a blood sample from the ipsilateral spermatic vein plexus and a peripheral blood sample were collected. A radioimmunoassay was performed to determine the total testosterone, free testosterone, dihydrotestosterone and oestradiol levels. An enzyme-linked immunosorbent assay was performed to determine the albumin level. The mean age of the patients was 32.3 +/- 9.3 years. Compared with the hormone level in the peripheral blood, the total testosterone, free testosterone, dihydrotestosterone, and oestrogen levels were significantly increased in the left or right spermatic vein plexus (P < 0.05). There were no differences in the albumin levels in the peripheral blood and spermatic vein plexus (P > 0.05). The mean total testosterone, free testosterone, dihydrotestosterone, and oestradiol levels in the left spermatic vein plexus were 10.8-fold, 29.0-fold, 2.0-fold, and 26.6-fold those of the peripheral blood. The hormone concentration in the spermatic vein plexus was significantly higher than that in the peripheral blood in patients with varicoceles. PMID- 26840998 TI - A Qualitative Study of the Maternity Care Experiences of Women with Obesity: "More than Just a Number on the Scale". AB - INTRODUCTION: The prevalence of obesity among pregnant women in the United States is high. Obesity can have long-term health consequences for both women and their offspring, so high-quality perinatal care for women with obesity is essential. However, stigmatizing encounters with health care professionals can decrease quality and promote avoidance of care. The purpose of this study was to explore the experiences of women with obesity in the maternity care system in the United States. METHODS: In-depth telephone interviews were conducted with 16 women with a body mass index of 30 or greater. The authors used an inductive analytical process to translate women's experiences into themes. RESULTS: Women with obesity reported diverse maternity care experiences, with some reporting appropriate and satisfactory care, while most reported at least one negative encounter over the course of perinatal care. Three major themes emerged from the analysis: personalized care, depersonalized care, and setting the tone. DISCUSSION: Interactions with providers during pregnancy had psychological and emotional effects on women with obesity and influenced the content and perceived quality of their care. Further research is required to explore this phenomenon and its implications for care of women during pregnancy and birth outcomes. In the meantime, providers may wish to consider greater sensitivity to the needs of women with obesity during the perinatal period. PMID- 26840999 TI - Morbidly obese and super-obese women should have surgery refused for benign conditions: FOR: A holistic approach is required to tackle the obesity pandemic and its effects. PMID- 26841000 TI - High-resolution 1 H-MRSI of the brain using short-TE SPICE. AB - PURPOSE: To improve signal-to-noise ratio (SNR) for high-resolution spectroscopic imaging using a subspace-based technique known as SPectroscopic Imaging by exploiting spatiospectral CorrElation (SPICE). METHODS: The proposed method is based on a union-of-subspaces model of MRSI signals, which exploits the partial separability properties of water, lipid, baseline and metabolite signals. Enabled by this model, a special scheme is used for accelerated data acquisition, which includes a double-echo CSI component used to collect a "training" dataset (for determination of the basis functions) and a short-TE EPSI component used to collect a sparse "imaging" dataset (for determination of the overall spatiospectral distributions). A set of signal processing algorithms are developed to remove the water and lipid signals and jointly reconstruct the metabolite and baseline signals. RESULTS: In vivo 1 H-MRSI results show that the proposed method can effectively remove the remaining water and lipid signals from sparse MRSI data acquired at 20 ms TE. Spatiospectral distributions of metabolite signals at 2 mm in-plane resolution with good SNR were obtained in a 15.5 min scan. CONCLUSIONS: The proposed method can effectively remove nuisance signals and reconstruct high-resolution spatiospectral functions from sparse data to make short-TE SPICE possible. The method should prove useful for high-resolution 1 H MRSI of the brain. Magn Reson Med 77:467-479, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26841001 TI - Characterization of Lipoyl Synthase from Mycobacterium tuberculosis. AB - The prevalence of multiple and extensively drug-resistant strains of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is on the rise, necessitating the identification of new targets to combat an organism that has infected one-third of the world's population, according to the World Health Organization. The biosynthesis of the lipoyl cofactor is one possible target, given its critical importance in cellular metabolism and the apparent lack of functional salvage pathways in Mtb that are found in humans and many other organisms. The lipoyl cofactor is synthesized de novo in two committed steps, involving the LipB-catalyzed transfer of an octanoyl chain derived from fatty acid biosynthesis to a lipoyl carrier protein and the LipA-catalyzed insertion of sulfur atoms at C6 and C8 of the octanoyl chain. A number of in vitro studies of lipoyl synthases from Escherichia coli, Sulfolobus solfataricus, and Thermosynechococcus elongatus have been conducted, but the enzyme from Mtb has not been characterized. Herein, we show that LipA from Mtb contains two [4Fe-4S] clusters and converts an octanoyl peptide substrate to the corresponding lipoyl peptide product via the same C6-monothiolated intermediate as that observed in the E. coli LipA reaction. In addition, we show that LipA from Mtb forms a complex with the H protein of the glycine cleavage system and that the strength of association is dependent on the presence of S-adenosyl-l-methionine. We also show that LipA from Mtb can complement a lipA mutant of E. coli, demonstrating the commonalities of the two enzymes. Lastly, we show that the substrate for LipA, which normally acts on a post-translationally modified protein, can be reduced to carboxybenzyl-octanoyllysine. PMID- 26841003 TI - Carbohydrate gel ingestion during running in the heat on markers of gastrointestinal distress. AB - The purpose of this study is to measure the effects of carbohydrate ingestion during exercise in the heat by measuring markers of gastrointestinal damage and inflammation. METHODS: Active subjects (n = 7) completed two 60-min running trials in a heated environment (70% VO2max, 30 degrees C). At minute 20 of exercise, subjects consumed a carbohydrate gel (Cho) (27 g), or a non carbohydrate placebo (nCho). Plasma endotoxin, I-FABP, TNF-alpha, IL-6, IL-1beta, IL-10, and MCP-1 were measured pre-exercise, 20-min post-exercise, and again 2-h, and 4-h post-exercise. RESULTS: Endotoxin increased 20-min post-exercise compared to pre in the Cho trial only (p = .03). I-FABP levels increased 20-min post exercise in the Cho trial only compared to pre-exercise (p = .003). I-FABP levels were also increased in Cho trial 20-min post-exercise when compared to same time point in the nCho trial (p = .032). TNF-alpha increased 20-min post-exercise in the Cho trial only compared to pre (p = .03). Plasma IL-6 concentration increased 20-min post-exercise when compared to pre in both the Cho (p = .002) and nCho (p = .009), but remained elevated at the 2-h time point in the nCho trial (p = .03). I-FABP and several plasma cytokines (TNF-alpha, MCP-1, Il-6) returned to baseline sooner in the Cho trial. CONCLUSIONS: Ingestion of carbohydrate gel during exercise in the heat enhances markers of gastrointestinal wall damage. PMID- 26841005 TI - Virology, serology, and demography of hepatitis E viremic blood donors in South East England. AB - BACKGROUND: Hepatitis E virus (HEV) Genotype 3 (G3) in England comprises two principal phylogenetic groups (Group 1 and Group 2) and can be transmitted by transfusion. Unselected screening identified 79 viremic donors; 76 participated in a follow-up study. STUDY DESIGN AND METHODS: Viral RNA dynamics, phylogenetics, and seroconversion were characterized in the donors. Detailed demographic, travel, clinical, and lifestyle questionnaires were undertaken. RESULTS: The majority of viremic individuals (57/79) were seronegative at time of donation but all seroconverted. Viremia was short-lived, with a median of 6.5 weeks to confirmed viral clearance. All infections were acquired in the United Kingdom and were G3, with Group 2 viruses predominating (43/54; 80%). Infection was associated with some clinical symptoms both at and after donation (8/77; 10%). Viral loads and symptoms were more pronounced in Group 1 infections. There was no serologic evidence of reinfection. Donors were more commonly male (p = 0.002); both male and female donors were older than comparator donors. Animal contact was unlikely to be the source of infection. Consumption of chicken and pig meat was common to all infected donors; processed pig meat was most commonly purchased from one particular retail chain. CONCLUSION: Viremic donors represent primary infection in older members of the community and reflect a widespread zoonotic in the United Kingdom. The two phylogenetic groups of HEV G3 display different pathogenicity and the more common Group 2 appears less adapted to humans. There are no objective demographic criteria that can identify donors at enhanced HEV risk. PMID- 26841002 TI - Development of composite outcomes for individual patient data (IPD) meta-analysis on the effects of diet and lifestyle in pregnancy: a Delphi survey. AB - OBJECTIVE: To develop maternal, fetal, and neonatal composite outcomes relevant to the evaluation of diet and lifestyle interventions in pregnancy by individual patient data (IPD) meta-analysis. DESIGN: Delphi survey. SETTING: The International Weight Management in Pregnancy (i-WIP) collaborative network. Sample Twenty-six researchers from the i-WIP collaborative network from 11 countries. METHODS: A two-generational Delphi survey involving members of the i WIP collaborative network (26 members in 11 countries) was undertaken to prioritise the individual outcomes for their importance in clinical care. The final components of the composite outcomes were identified using pre-specified criteria. MAIN OUTCOME MEASURES: Composite outcomes considered to be important for the evaluation of the effect of diet and lifestyle in pregnancy. RESULTS: Of the 36 maternal outcomes, nine were prioritised and the following were included in the final composite: pre-eclampsia or pregnancy-induced hypertension, gestational diabetes mellitus (GDM), elective or emergency caesarean section, and preterm delivery. Of the 27 fetal and neonatal outcomes, nine were further evaluated, with the final composite consisting of intrauterine death, small for gestational age, large for gestational age, and admission to a neonatal intensive care unit (NICU). CONCLUSIONS: Our work has identified the components of maternal, fetal, and neonatal composite outcomes required for the assessment of diet and lifestyle interventions in pregnancy by IPD meta-analysis. PMID- 26841006 TI - A systematic review and meta-analysis on the longitudinal relationship between eating pathology and depression. AB - OBJECTIVE: Undertake a meta-analysis to provide a quantitative synthesis of longitudinal studies that assessed the direction of effects between eating pathology and depression. A second aim was to use meta-regression to account for heterogeneity in terms of study-level effect modifiers. METHOD: A systematic review was conducted on 42 studies that assessed the longitudinal relationship between eating pathology and depression. Of these 42 studies, multilevel random effects meta-analyses were conducted on 30 eligible studies. RESULTS: Meta analysis results showed that eating pathology was a risk factor for depression (rm = 0.13) and that depression was a risk factor for eating pathology (rm = 0.16). Meta-regression analyses showed that these effects were significantly stronger for studies that operationalized eating pathology as an eating disorder diagnosis versus eating pathology symptoms, and for studies that operationalized the respective outcome measure as a categorical variable (e.g., a diagnosis of a disorder or where symptoms were "present"/"absent") versus a continuous measure. Results also showed that in relation to eating pathology type, the effect of an eating disorder diagnosis and bulimic symptoms on depression was significantly stronger for younger participants. DISCUSSION: Eating pathology and depression are concurrent risk factors for each other, suggesting that future research would benefit from identifying factors that are etiological to the development of both constructs. RESUMEN OBJETIVO: Llevar a cabo un meta-analisis para proporcionar una sintesis cuantitativa de los estudios longitudinales que evaluaron la direccion de los efectos entre la alimentacion patologica y la depresion. Un segundo objetivo fue utilizar la meta-regresion para dar cuenta de la heterogeneidad en terminos de modificadores del efecto a nivel de estudio. METODO: Una revision sistematica se llevo a cabo en 42 estudios que evaluaron la relacion longitudinal entre la alimentacion patologica y la depresion. De estos 42 estudios, se realizaron meta-analisis de multinivel de efectos aleatorios en 30 estudios elegibles. RESULTADOS: Los resultados del meta-analisis mostraron que la alimentacion patologica era un factor de riesgo para depresion (rm=0.13) y que la depresion era un factor de riesgo para la alimentacion patologica (rm=0.16). Los analisis de meta-regresion mostraron que estos efectos eran significativamente mas fuertes para estudios que operacionalizaban la alimentacion patologica como un diagnostico de trastorno de la conducta alimentaria versus sintomas de alimentacion patologica, y para los estudios que operacionalizaban la medida respectiva de resultado como una variable categorica (e.g., un diagnostico de trastorno o cuando los sintomas estaban "presentes"/"ausentes") versus una medida continua. Los resultados mostraron que en relacion al tipo de alimentacion patologica, el efecto de un diagnostico de trastorno de la conducta alimentaria y sintomas bulimicos en la depresion era significativamente mas fuerte para participantes mas jovenes. DISCUSION: La alimentacion patologica y la depresion son factores de riesgo concurrentes uno para el otro, lo que sugiere que la investigacion futura se beneficiaria de identificar factores que son etiologicos al desarrollo de ambos constructos. (c) 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2016;49:439-454). PMID- 26841007 TI - Critical Patient Severity Classification System predicts outcomes in intensive care unit patients. AB - BACKGROUND: The CPSCS was developed to assess the nursing care demands of patients in intensive care units (ICUs). AIM: This study aimed to examine the Critical Patient Severity Classification System (CPSCS) score as an independent predictor of patient hospital outcomes. DESIGN: This study was a secondary analysis. METHODS: Data from 6380 cases were extracted from the electronic medical records in ICUs at a tertiary hospital in Korea during 2010-2012. To examine the association of the CPSCS score with 30-day ICU mortality, the Cox proportional hazards model and Kaplan-Meier survival curves were used, and generalized linear regression models of gamma distribution were developed for ICU length of stay (LOS). RESULTS: More patients were admitted to surgical ICUs than medical ICUs (4664 versus 1716) during the study period. Medical ICU patients had longer ICU LOS, higher 30-day ICU mortality and a higher mean CPSCS score than surgical ICU patients. Cox analysis indicated that the mid and high CPSCS score groups had 1.687 and 2.913 times higher mortality risk, respectively, than the low CPSCS score group after adjusting for age, sex and primary diagnosis. The CPSCS score significantly predicted ICU mortality in both medical and surgical ICUs. Multivariate generalized linear regression indicated that CPSCS score was a significant predictor of ICU LOS after adjusting for other covariates. CONCLUSIONS: The CPSCS score can be used to efficiently predict ICU mortality and LOS in patients admitted to the medical and surgical ICUs, although only the high CPSCS score group had significantly high mortality than the low CPSCS score group in the medical ICU. RELEVANCE TO CLINICAL PRACTICE: The findings of this study contribute to valuable evidence that nursing-related factors have an impact on patient outcomes such as ICU mortality and LOS and that they have implications for hospital management, clinical practice and future research. PMID- 26841008 TI - From the Guest Editor: Hematologic Cancers: A Decade of Progress in Targeted Therapy. PMID- 26841009 TI - Monoclonal Antibodies for the Treatment of Myeloma: Targeting SLAMF7 and CD38. AB - The recent explosion of immune-based treatments for cancer has significantly impacted remission durations and overall survival for many diseases. Multiple myeloma is no exception to this trend, with several immune-based treatments including checkpoint blockade, cellular therapy, and most advanced now antibody based treatment coming to fruition. While the use of monoclonal antibodies has been a significant interest in myeloma for some time, identifying the ideal target has been an issue. Given the dependence of plasma cells on interleukin 6 signaling for survival and proliferation, there were several trials testing both single agent and combination therapy effects of anti-interleukin 6 antibodies, which did not demonstrate significant clinical activity; however, more recent antibodies targeting receptors such as CD38 and SLAMF7 (previously known as CS1) are demonstrating significant clinical benefit. In this article, we briefly review the preclinical and clinical data surrounding these 2 important targets and the antibodies that clinically will be used as therapeutic agents in the context of multiple myeloma. PMID- 26841010 TI - Inhibitors of the Cyclin-Dependent Kinase and PIM Kinase Pathways in the Treatment of Myeloma. AB - Multiple myeloma (MM) cells are characterized by genomic alternations that lead to increased cell proliferation and resistance to therapeutic interventions. Up regulation of cyclins is a characteristic finding in a significant proportion of myeloma patients, mediated through a variety of mechanisms including chromosomal translocations. Cyclins and the cyclin-dependent kinases (CDKs) play a critical role in the cell proliferation seen in MM, especially in the high-risk disease. Given this, CDK inhibitors have been evaluated in this disease, and studies so far have led to a mixed picture. Recent studies with targeted CDK inhibitors have shown early promise, and trials of these drugs in combination with other myeloma drugs are ongoing. The malignant plasma cells in MM are highly dependent on the microenvironment for their growth and survival. Multiple signaling pathways have been found to mediate the interactions between the microenvironment and the plasma cells, whether mediated through cytokines or adhesion molecules. The PIM kinase pathway appears to play a major role in the myeloma cell survival, and PIM kinase inhibitors have shown efficacy in the laboratory, and a recent clinical trial also demonstrates important clinical activity. PMID- 26841011 TI - Idelalisib: Targeting the PI3 Kinase Pathway in Non-Hodgkin Lymphoma. AB - Based on substantial preclinical rationale, the restricted hematopoietic expression of the delta isoform of the phosphatidylinositol 3-kinase represents an attractive therapeutic target in B-cell malignancies. Its inhibition results in a direct antiproliferative effect on tumor cells as well as several modifications of their cellular microenvironment, all accounting for the potential therapeutic interest. Idelalisib, the first-in-class phosphatidylinositol 3-kinase delta-specific inhibitor, was developed in patients with B-cell lymphomas and chronic lymphocytic leukemia. Early clinical results demonstrated a potent antitumor effect across different subtypes of indolent and mantle cell lymphomas (where response duration was short). Adverse events, including transaminitis, neutropenia, pneumonitis, and diarrhea, were observed. A pivotal phase II study in patients with double refractory disease showed a 57% response rate, with response lasting for about 1 year, leading to market approval of the drug in the United States and Europe. Further developments of idelalisib combinations will contribute to delineate the position of this drug in the therapeutic strategy of indolent lymphomas. PMID- 26841012 TI - Checkpoint Inhibition: Programmed Cell Death 1 and Programmed Cell Death 1 Ligand Inhibitors in Hodgkin Lymphoma. AB - Hodgkin lymphoma (HL) is a lymphoid malignancy characterized by a reactive immune infiltrate surrounding relatively few malignant cells. In this scenario, active immune evasion seems to play a central role in allowing tumor progression. Immune checkpoint inhibitor pathways are normal mechanisms of T-cell regulation that suppress immune effector function following an antigenic challenge. Hodgkin lymphoma cells are able to escape immune surveillance by co-opting these mechanisms. The programmed cell death 1 (PD-1) pathway in particular is exploited in HL as the malignant Hodgkin and Reed-Sternberg cells express on their surface cognate ligands (PD-L1/L2) for the PD-1 receptor and thereby dampen the T-cell mediated antitumoral response. Monoclonal antibodies that interact with and disrupt the PD-1:PD-L1/L2 axis have now been developed and tested in early-phase clinical trials in patients with advanced HL with encouraging results. The remarkable clinical activity of PD-1 inhibitors in HL highlights the importance of immune checkpoint pathways as therapeutic targets in HL. In this review, we discuss the rationale for targeting PD-1 and PD-L1 in the treatment of HL. We will evaluate the published clinical data on the different agents and highlight the safety profile of this class of agents. We discuss the available evidence on the use of biomarkers as predictors of response to checkpoint blockade and summarize the areas under active investigation in the use of PD-1/PD-L1 inhibitors for the treatment of HL. PMID- 26841013 TI - Targeting CD30 Using Brentuximab Vedotin in the Treatment of Hodgkin Lymphoma. AB - The expression of CD30 receptors is one of the defining characteristics of the malignant Reed-Sternberg cells of Hodgkin lymphoma (HL). CD30 is rarely expressed by normal cells and is rapidly internalized, making it an ideal therapeutic target for monoclonal antibodies and for antibody-drug conjugates. Brentuximab vedotin is the first antibody-drug conjugate to be approved by regulatory agencies for the treatment of patients with relapsed HL, with a single-agent response rate of 75%. In this review article, we discuss the current and ongoing development of brentuximab vedotin in patients with relapsed and newly diagnosed HL. PMID- 26841014 TI - The Promise of Chimeric Antigen Receptor Engineered T Cells in the Treatment of Hematologic Malignancies. AB - Relapsed and refractory hematologic malignancies have a very poor prognosis. Chimeric antigen receptor T cells are emerging as a powerful therapy in this setting. Early clinical trials of genetically modified T cells for the treatment of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia have shown high complete response rates in patients with few therapeutic options. Exploration is ongoing for other hematologic malignancies including multiple myeloma, acute myeloid leukemia, and Hodgkin lymphoma (HL). At the same time, the design and production of chimeric antigen receptor T cells are being advanced so that this therapy can be more widely utilized. Cytokine release syndrome and neurotoxicity are common, but they are treatable and fully reversible. This review will review available data as well as future developments and challenges in the field. PMID- 26841015 TI - Inhibition of the Bruton Tyrosine Kinase Pathway in B-Cell Lymphoproliferative Disorders. AB - Activation of the Bruton tyrosine kinase (BTK) pathway plays an important role in the pathophysiology of a number of B-cell lymphoproliferative disorders (LPDs). A number of preclinical studies support inhibiting BTK as a mechanism to treat LPDs. Clinically, BTK inhibitors, specifically ibrutinib, have shown to be safe and effective on treating patients with indolent B-cell lymphomas and chronic lymphocytic leukemia (CLL). Ibrutinib has recently gained approval for the treatment of patients with mantle cell lymphoma, Waldenstrom macroglobulinemia, and CLL. Ongoing clinical trials are investigating ibrutinib and other BTK inhibitors alone or in combination for the treatment of mantle cell lymphoma, Waldenstrom macroglobulinemia, CLL, activated B-cell-type diffuse large B-cell lymphoma, and follicular lymphoma, among others. The objective of this review is to succinctly summarize the current body of evidence on BTK inhibition in patients with B-cell LPDs. PMID- 26841017 TI - Treatment of Myelofibrosis: A Moving Target. AB - Myelofibrosis (MF) is a myeloproliferative neoplasm that presents either as a primary disease or evolves secondarily from polycythemia vera or essential thrombocythemia to post-polycythemia vera MF or post-essential thrombocythemia MF, respectively. Myelofibrosis is characterized by stem cell-derived clonal myeloproliferation, abnormal cytokine expression, bone marrow fibrosis, anemia, splenomegaly, extramedullary hematopoiesis, constitutional symptoms, cachexia, leukemic progression, and shortened survival. Therapeutic options for patients with MF have been limited to the use of cytoreductive agents, predominantly hydroxyurea; splenectomy and splenic irradiation for treatment of splenomegaly; and management of anemia with transfusions, erythropoiesis-stimulating agents, androgens, and immunomodulatory agents along with steroids. The only curative option is allogeneic stem cell transplantation (ASCT), which is associated with high morbidity and mortality risks. Recently, JAK (Janus kinase) inhibitor therapies have become available and proven to be palliative in primary MF patients with hydroxyurea-refractory splenomegaly and severe constitutional symptoms. The purpose of this article is to review the clinical features of MF; discuss different treatment strategies, including ASCT; and discuss the potential danger and benefit of using JAK inhibitors prior to ASCT. PMID- 26841016 TI - The Role of New Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia. AB - Imatinib mesylate was the first tyrosine kinase inhibitor (TKI) approved for the management of chronic myeloid leukemia. Imatinib produces acceptable responses in approximately 60% of patients, with approximately 20% discontinuing therapy because of intolerance and approximately 20% developing drug resistance. The advent of newer TKIs, such as nilotinib, dasatinib, bosutinib, and ponatinib, has provided multiple options for patients. These agents are more potent, have unique adverse effect profiles, and are more likely to achieve relevant milestones, such as early molecular responses (3-6 months) and optimal molecular responses (12 months). The acquisition of BCR-ABL kinase domain mutations is also reportedly lower with these drugs. Thus far, none of the randomized phase III clinical trials have shown a clinically significant survival difference between frontline imatinib versus newer TKIs. Cost and safety issues with the newer TKIs, such as vascular disease with nilotinib and ponatinib and pulmonary hypertension with dasatinib, have dampened the enthusiasm of using these drugs as frontline options. While the utility of new TKIs in the setting of imatinib failure or intolerance is clear, their use as frontline agents should factor in the age of the patient, additional comorbidities, risk stratification (Sokal score), and cost. Combination therapies and newer agents with potential to eradicate quiescent chronic myeloid leukemia stem cells offers future hope. PMID- 26841018 TI - Combination of Targeted Drugs to Control Chronic Lymphocytic Leukemia: Harnessing the Power of New Monoclonal Antibodies in Combination With Ibrutinib. AB - The landscape of treatment for chronic lymphocytic leukemia is rapidly changing at present. Considerable improvement has been achieved with the introduction of the anti-CD20 antibodies, and chemoimmunotherapy has now become an established standard for patients without the high-risk features del(17p)/TP53 mutation. Also, the outcome of patients with these adverse genetic aberrations was dramatically improved with the introduction of the kinase inhibitors ibrutinib and idelalisib. Different combinations of these and additional novel agents are currently evaluated in clinical trials. The combination of the Bruton tyrosine kinase inhibitor ibrutinib with an anti-CD20 antibody is an attractive option, because both drugs act synergistically: ibrutinib redistributes the CLL cells from their homing organs to the peripheral blood, and obinutuzumab eliminates the leukemic cells in the blood with particular efficiency. Adding the Bcl-2 antagonist venetoclax could further intensify the treatment of CLL. This combination might hold the potential to achieve a deep remission with an eradication of residual CLL cells and thus lead to long-term remissions of CLL. PMID- 26841019 TI - Dependence measures based on hookah smokers' experiences and context are needed. PMID- 26841021 TI - A New Animal Model for Investigation of Mechanical Unloading in Hypertrophic and Failing Hearts: Combination of Transverse Aortic Constriction and Heterotopic Heart Transplantation. AB - OBJECTIVES: Previous small animal models for simulation of mechanical unloading are solely performed in healthy or infarcted hearts, not representing the pathophysiology of hypertrophic and dilated hearts emerging in heart failure patients. In this article, we present a new and economic small animal model to investigate mechanical unloading in hypertrophic and failing hearts: the combination of transverse aortic constriction (TAC) and heterotopic heart transplantation (hHTx) in rats. METHODS: To induce cardiac hypertrophy and failure in rat hearts, three-week old rats underwent TAC procedure. Three and six weeks after TAC, hHTx with hypertrophic and failing hearts in Lewis rats was performed to induce mechanical unloading. After 14 days of mechanical unloading animals were euthanatized and grafts were explanted for further investigations. RESULTS: 50 TAC procedures were performed with a survival of 92% (46/50). When compared to healthy rats left ventricular surface decreased to 5.8+/-1.0 mm2 (vs. 9.6+/- 2.4 mm2) (p = 0.001) after three weeks with a fractional shortening (FS) of 23.7+/- 4.3% vs. 28.2+/- 1.5% (p = 0.01). Six weeks later, systolic function decreased to 17.1+/- 3.2% vs. 28.2+/- 1.5% (p = 0.0001) and left ventricular inner surface increased to 19.9+/-1.1 mm2 (p = 0.0001). Intraoperative graft survival during hHTx was 80% with 46 performed procedures (37/46). All transplanted organs survived two weeks of mechanical unloading. DISCUSSION: Combination of TAC and hHTx in rats offers an economic and reproducible small animal model enabling serial examination of mechanical unloading in a truly hypertrophic and failing heart, representing the typical pressure overloaded and dilated LV, occurring in patients with moderate to severe heart failure. PMID- 26841020 TI - Work Engagement as a Predictor of Onset of Major Depressive Episode (MDE) among Workers, Independent of Psychological Distress: A 3-Year Prospective Cohort Study. AB - OBJECTIVE: This study investigated work engagement as a baseline predictor of onset of major depressive episode (MDE). METHODS: The study used a prospective cohort design, conforming to the STROBE checklist. Participants were recruited from the employee population of a private think tank company (N = 4,270), and 1,058 (24.8%) of them completed a baseline survey, of whom 929 were included in this study. Work engagement and psychological distress at baseline were assessed as predictor variables. MDE was measured at baseline and at each of the follow ups as the outcome, using the web-based, self-administered version of the Japanese WHO-CIDI 3.0 depression section based upon DSM-IV-TR/DSM-5 criteria. Cox discrete-time hazards analyses were conducted to estimate hazard ratios (95% confidence intervals CIs). RESULTS: Follow-up rates of participants (N = 929) were 78.4%, 67.2%, and 51.6% at 1-, 2-, and 3-year follow-ups, respectively. The association between work engagement at baseline and the onset of MDE was U shaped. Compared with a group with low work engagement scores, groups with the middle and high scores showed significantly (HR = 0.19, 95% CI = 0.05 to 0.64; p = 0.007) and marginally significantly (HR = 0.48, 95% CI = 0.20 to 1.15, p = 0.099) lower risks of MDE, respectively, over the follow-ups, after adjusting for covariates. The pattern remained the same after additionally adjusting for psychological distress. CONCLUSIONS: The present study first demonstrated work engagement as an important predictor of the onset of MDE diagnosed according to an internationally standard diagnostic criteria of mental disorders. PMID- 26841022 TI - Antenatal Corticosteroids for Reducing Adverse Maternal and Child Outcomes in Special Populations of Women at Risk of Imminent Preterm Birth: A Systematic Review and Meta-Analysis. AB - BACKGROUND: This study synthesizes available evidence on antenatal corticosteroids (ACS) use among special subgroups of women at risk of imminent preterm birth, including those (1) with pregestational and gestational diabetes mellitus, (2) undergoing elective caesarean section (CS) in late preterm (34 to<37 weeks), (3) with chorioamnionitis, and (4) with growth-restricted fetuses. METHODS: A systematic search of MEDLINE, EMBASE, CINAHL, Cochrane Library, POPLINE, and World Health Organization Regional Databases was conducted for all comparative studies. Two reviewers independently determined study eligibility, extracted data, and assessed study quality. Pooled mean differences and odds ratios with 95% confidence intervals were estimated from available data, based on fixed- and random-effects models, as appropriate. RESULTS: No eligible studies were identified for ACS use in diabetic pregnant women or those undergoing elective CS at late preterm. Nine studies each on ACS use in women with chorioamnionitis and in women with fetal growth restriction met inclusion criteria; eight studies were separately included in the meta-analyses for the two subpopulations. For ACS administration in women with chorioamnionitis, pooled analyses showed reductions in neonatal mortality (OR: 0.49, 95% CI: 0.34-0.73), respiratory distress syndrome (OR: 0.58, 95% CI: 0.44-0.76), intraventricular haemorrhage (OR: 0.41, 95% CI: 0.24-0.69), and severe intraventricular haemorrhage (OR: 0.40, 95% CI: 0.24-0.69). Maternal and long-term newborn outcomes were not reported. Effects of ACS use were inconclusive for cases with fetal growth restriction. CONCLUSION: Direct evidence on the effectiveness and safety of ACS is lacking for diabetic pregnant women at risk of preterm birth and those undergoing elective late-preterm CS, though this does not necessarily recommend against their use in diabetic women. While evidence remains inconclusive for women with growth-restricted preterm neonates, ACS appears to benefit preterm neonates delivered by women with chorioamnionitis. High-quality studies on maternal and long-term child outcomes in more diverse settings are needed to establish the balance of potential harms versus benefits in using ACS for these understudied subgroups. PMID- 26841023 TI - Open-Source Selective Laser Sintering (OpenSLS) of Nylon and Biocompatible Polycaprolactone. AB - Selective Laser Sintering (SLS) is an additive manufacturing process that uses a laser to fuse powdered starting materials into solid 3D structures. Despite the potential for fabrication of complex, high-resolution structures with SLS using diverse starting materials (including biomaterials), prohibitive costs of commercial SLS systems have hindered the wide adoption of this technology in the scientific community. Here, we developed a low-cost, open-source SLS system (OpenSLS) and demonstrated its capacity to fabricate structures in nylon with sub millimeter features and overhanging regions. Subsequently, we demonstrated fabrication of polycaprolactone (PCL) into macroporous structures such as a diamond lattice. Widespread interest in using PCL for bone tissue engineering suggests that PCL lattices are relevant model scaffold geometries for engineering bone. SLS of materials with large powder grain size (~500 MUm) leads to part surfaces with high roughness, so we further introduced a simple vapor-smoothing technique to reduce the surface roughness of sintered PCL structures which further improves their elastic modulus and yield stress. Vapor-smoothed PCL can also be used for sacrificial templating of perfusable fluidic networks within orthogonal materials such as poly(dimethylsiloxane) silicone. Finally, we demonstrated that human mesenchymal stem cells were able to adhere, survive, and differentiate down an osteogenic lineage on sintered and smoothed PCL surfaces, suggesting that OpenSLS has the potential to produce PCL scaffolds useful for cell studies. OpenSLS provides the scientific community with an accessible platform for the study of laser sintering and the fabrication of complex geometries in diverse materials. PMID- 26841024 TI - iTRAQ-Based Quantitative Proteomic Analysis of Cotton Roots and Leaves Reveals Pathways Associated with Salt Stress. AB - Salinity is a major abiotic stress that affects plant growth and development. In this study, we performed a proteomic analysis of cotton roots and leaf tissue following exposure to saline stress. 611 and 1477 proteins were differentially expressed in the roots and leaves, respectively. In the roots, 259 (42%) proteins were up-regulated and 352 (58%) were down-regulated. In the leaves, 748 (51%) proteins were up-regulated and 729 (49%) were down-regulated. On the basis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, we concluded that the phenylalanine metabolism and starch and sucrose metabolism were active for energy homeostasis to cope with salt stress in cotton roots. Moreover, photosynthesis, pyruvate metabolism, glycolysis / gluconeogenesis, carbon fixation in photosynthetic organisms and phenylalanine metabolism were inhabited to reduce energy consumption. Characterization of the signaling pathways will help elucidate the mechanism activated by cotton in response to salt stress. PMID- 26841026 TI - Pediatric Acute Respiratory Distress Syndrome: Which Child Is Destined to Die? PMID- 26841025 TI - Vaccination with an Attenuated Mutant of Ehrlichia chaffeensis Induces Pathogen Specific CD4+ T Cell Immunity and Protection from Tick-Transmitted Wild-Type Challenge in the Canine Host. AB - Ehrlichia chaffeensis is a tick-borne rickettsial pathogen and the causative agent of human monocytic ehrlichiosis. Transmitted by the Amblyomma americanum tick, E. chaffeensis also causes disease in several other vertebrate species including white-tailed deer and dogs. We have recently described the generation of an attenuated mutant strain of E. chaffeensis, with a mutation in the Ech_0660 gene, which is able to confer protection from secondary, intravenous administered, wild-type E. chaffeensis infection in dogs. Here, we extend our previous results, demonstrating that vaccination with the Ech_0660 mutant protects dogs from physiologic, tick-transmitted, secondary challenge with wild type E. chaffeensis; and describing, for the first time, the cellular and humoral immune responses induced by Ech_0660 mutant vaccination and wild-type E. chaffeensis infection in the canine host. Both vaccination and infection induced a rise in E. chaffeensis-specific antibody titers and a significant Th1 response in peripheral blood as measured by E. chaffeensis antigen-dependent CD4+ T cell proliferation and IFNgamma production. Further, we describe for the first time significant IL-17 production by peripheral blood leukocytes from both Ech_0660 mutant vaccinated animals and control animals infected with wild-type E. chaffeensis, suggesting a previously unrecognized role for IL-17 and Th17 cells in the immune response to rickettsial pathogens. Our results are a critical first step towards defining the role of the immune system in vaccine-induced protection from E. chaffeensis infection in an incidental host; and confirm the potential of the attenuated mutant clone, Ech_0660, to be used as a vaccine candidate for protection against tick-transmitted E. chaffeensis infection. PMID- 26841027 TI - Measuring and Improving, Not Just Describing-The Next Imperative for End-of-Life Care. PMID- 26841028 TI - Predicting Acute Kidney Injury After Pediatric Cardiac Surgery: Are Steroids Muddying the Water? PMID- 26841029 TI - Aminophylline for Acute Kidney Injury After Pediatric Cardiac Surgery: Finally Entering the Next Phase in Child Acute Kidney Injury Research. PMID- 26841030 TI - Intra-Abdominal Pressure Monitoring in Neonates. PMID- 26841031 TI - Comparing Apples and Oranges: Seizure Prophylaxis in Pediatric Traumatic Brain Injury. PMID- 26841032 TI - Unanswered Questions and Consternation: The Ventilator-Associated Pneumonia Diagnostic Challenge Continues. PMID- 26841033 TI - High-Dose Magnesium Infusions for Acute Severe Asthma in Children: If a Little Is Good, Is More Even Better? PMID- 26841034 TI - Children Are Not Just Little Adults.... PMID- 26841035 TI - Admission Hypoalbuminemia: Ready for Including It in the Pediatric Prognostic Scores? PMID- 26841036 TI - Evidence-Based Use of alpha-2 Agonists for Sedation in the PICU: From Fiction to Facts? PMID- 26841037 TI - Still a Way to Go: The Substitution of the x-Ray as the Gold Standard to Locate the Right Placement of Central Venous Catheter. PMID- 26841038 TI - The authors reply. PMID- 26841039 TI - Noninvasive Ventilation in Pediatric Acute Respiratory Distress Syndrome. Where Is the Limit? PMID- 26841040 TI - The authors reply. PMID- 26841041 TI - Aminolevulinic acid and methyl aminolevulinate equally effective in topical photodynamic therapy for non-melanoma skin cancers. AB - BACKGROUND: Topical photodynamic therapy (PDT) is an effective treatment for superficial non-melanoma skin cancers. Two prodrugs, 5-aminolevulinic acid (ALA) and methyl aminolevulinate (MAL), are available for clinical use. There is, however, a lack of studies comparing the clinical effectiveness of these two prodrugs. OBJECTIVE: The objective of the study was to compare the clinical response between ALA- and MAL-PDT when treating actinic keratosis (AK), Bowen's disease (BD), nodular basal cell carcinoma (nBCC) and superficial basal cell carcinoma (sBCC). METHODS: During the period 2002-2009, patients with AK, BD, nBCC and sBCC were treated with ALA- and MAL-PDT at the Department of Dermatology at Karlskoga Hospital in Sweden using a fixed protocol. All patients were followed up approximately 6 months after treatment to evaluate the clinical results, which were analysed retrospectively. RESULTS: In total, 116 patients with 203 tumours were treated with PDT during the study period. ALA- and MAL-PDT were used for 24 vs. 44 AK fields, 9 vs. 18 BD lesions, 19 vs. 25 nBCCs and 25 vs. 39 sBCCs. Response rates with ALA- and MAL-PDT, respectively, were 63% and 75% for AK, 89% and 78% for BD, 84% and 84% for nBCC and 88% and 87% for sBCC. There were no statistically significant differences in the complete clinical response rates for ALA- and MAL-PDT when used for any of the four lesion types. CONCLUSION: ALA- and MAL-PDT appear to be equally effective in the treatment of AK, BD, nBCC and sBCC. Nevertheless, larger, prospective, randomized and controlled studies should be carried out to confirm these results. PMID- 26841042 TI - Epidemiology of Idiopathic Pulmonary Fibrosis in Northern Italy. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of idiopathic interstitial pneumonia. Despite its clinical relevance, few studies have examined the epidemiology of IPF and temporal variation in disease incidence and prevalence. Aim of the study was to investigate the prevalence, incidence and trends of IPF in Lombardy, a region with nearly 10 million inhabitants, during 2005-2010. METHODS: For the identification of IPF patients, we used healthcare administrative databases of Lombardy Healthcare System and adopted three algorithms: generic, broad and narrow case definition (GCD, BCD, NCD). IPF cases were identified according to diagnoses reported in inpatient and outpatient claims occurred during 2000-2010. We estimated age- and sex-adjusted annual prevalence and incidence rates from 2005 to 2010, thus allowing for a 5 year washout period. RESULTS: The mean annual incidence rate was estimated at 2.3 and 5.3 per 100,000 person-years using NCD and GCD, respectively. IPF incidence was higher among males, and increased with age. Trend remained stable over the years. The estimated annual prevalence rate was 35.5, 22.4, and 12.6 per 100,000 person-years using GCD, BCD and NCD, respectively, and increased with age. Moreover, we observed a positive trend over the years. Using BCD and NCD, prevalence was higher among males. CONCLUSIONS: The results of this study, which is one of the largest population-based survey ever conducted according to strict criteria, indicated that prevalence of IPF increased across the years while incidence remained stable, thus suggesting that survival with IPF has improved. PMID- 26841043 TI - A Site-Specific Integrative Plasmid Found in Pseudomonas aeruginosa Clinical Isolate HS87 along with A Plasmid Carrying an Aminoglycoside-Resistant Gene. AB - Plasmids play critical roles in bacterial fitness and evolution of Pseudomonas aeruginosa. Here two plasmids found in a drug-resistant P. aeruginosa clinical isolate HS87 were completely sequenced. The pHS87b plasmid (11.2 kb) carries phage-related genes and function-unknown genes. Notably, pHS87b encodes an integrase and has an adjacent tRNAThr-associated attachment site. A corresponding integrated form of pHS87b at the tRNAThr locus was identified on the chromosome of P. aeruginosa, showing that pHS87b is able to site-specifically integrate into the 3'-end of the tRNAThr gene. The pHS87a plasmid (26.8 kb) displays a plastic structure containing a putative replication module, stability factors and a variable region. The RepA of pHS87a shows significant similarity to the replication proteins of pPT23A-family plasmids. pHS87a carries a transposon Tn6049, a truncated insertion sequence DeltaIS1071 and a Tn402-like class 1 integron which contains an aacA4 cassette that may confer aminoglycoside resistance. Thus, pHS87b is a site-specific integrative plasmid whereas pHS87a is a plastic antibiotic resistance plasmid. The two native plasmids may promote the fitness and evolution of P. aeruginosa. PMID- 26841044 TI - Development of a novel-type transgenic cotton plant for control of cotton bollworm. AB - The transgenic Bt cotton plant has been widely planted throughout the world for the control of cotton budworm Helicoverpa armigera (Hubner). However, a shift towards insect tolerance of Bt cotton is now apparent. In this study, the gene encoding neuropeptide F (NPF) was cloned from cotton budworm H. armigera, an important agricultural pest. The npf gene produces two splicing mRNA variants npf1 and npf2 (with a 120-bp segment inserted into the npf1 sequence). These are predicted to form the mature NPF1 and NPF2 peptides, and they were found to regulate feeding behaviour. Knock down of larval npf with dsNPF in vitro resulted in decreases of food consumption and body weight, and dsNPF also caused a decrease of glycogen and an increase of trehalose. Moreover, we produced transgenic tobacco plants transiently expressing dsNPF and transgenic cotton plants with stably expressed dsNPF. Results showed that H. armigera larvae fed on these transgenic plants or leaves had lower food consumption, body size and body weight compared to controls. These results indicate that NPF is important in the control of feeding of H. armigera and valuable for production of potential transgenic cotton. PMID- 26841045 TI - Human Stem Cells Overexpressing miR-21 Promote Angiogenesis in Critical Limb Ischemia by Targeting CHIP to Enhance HIF-1alpha Activity. AB - Critical limb ischemia (CLI) is a severe blockage in the arteries of the lower extremities. However, the effective and optimal treatment for CLI remains to be elucidated. Previous therapeutic research is mainly focused on proangiogenic growth factors administrations. Recently, miR-21 has been revealed to play a crucial role in angiogenesis. Thus, we hypothesize that miR-21 over-expression in human umbilical cord blood-derived mesenchymal stem cells (UCBMSCs) can effectively treat CLI. Herein, UCBMSCs were transduced with lentivirus-miR-21 Luciferase (Lenti-miR-21) or lentivirus- LacZ-Luciferase (Lenti-LacZ). The results indicated that miR-21 induced UCBMSCs proliferation, migration, and angiogenesis in vitro. Subsequently, general observation and laser Doppler perfusion imaging were introduced to detect perfusion in muscles of CLI-nude mice on 1, 4, 7, 14, and 28 day postoperation. There was a significant improvement in blood vessels of the ischemic limb in Lenti-miR-21 group at 7 day compared with the saline or Lenti-LacZ groups. At 28 day, histological analysis confirmed that UCBMSCs over-expressing miR-21 increased neovascularization in CLI. Furthermore, carboxyl terminus of Hsc70-interacting protein (CHIP) was found to be the target gene for miR-21-mediated activation of hypoxia-inducible factor 1alpha (HIF 1alpha) in UCBMSCs. In summary, our study demonstrated that over-expressing miR 21 in UCBMSCs could improve neovascularization in CLI through enhancing HIF 1alpha activity by targeting CHIP, which may hold great therapeutic promise in treating CLI. PMID- 26841047 TI - A molecular platform for the diagnosis of multidrug-resistant and pre-extensively drug-resistant tuberculosis based on single nucleotide polymorphism mutations present in Colombian isolates of Mycobacterium tuberculosis. AB - Developing a fast, inexpensive, and specific test that reflects the mutations present in Mycobacterium tuberculosis isolates according to geographic region is the main challenge for drug-resistant tuberculosis (TB) control. The objective of this study was to develop a molecular platform to make a rapid diagnosis of multidrug-resistant (MDR) and extensively drug-resistant TB based on single nucleotide polymorphism (SNP) mutations present in therpoB, katG, inhA,ahpC, and gyrA genes from Colombian M. tuberculosis isolates. The amplification and sequencing of each target gene was performed. Capture oligonucleotides, which were tested before being used with isolates to assess the performance, were designed for wild type and mutated codons, and the platform was standardised based on the reverse hybridisation principle. This method was tested on DNA samples extracted from clinical isolates from 160 Colombian patients who were previously phenotypically and genotypically characterised as having susceptible or MDR M. tuberculosis. For our method, the kappa index of the sequencing results was 0,966, 0,825, 0,766, 0,740, and 0,625 forrpoB, katG, inhA,ahpC, and gyrA, respectively. Sensitivity and specificity were ranked between 90-100% compared with those of phenotypic drug susceptibility testing. Our assay helps to pave the way for implementation locally and for specifically adapted methods that can simultaneously detect drug resistance mutations to first and second-line drugs within a few hours. PMID- 26841048 TI - Complete genome of a dengue virus serotype 4 strain from Amazonas, Brazil. AB - Dengue virus (DENV) infections represent a significant concern for public health worldwide, being considered as the most prevalent arthropod-borne virus regarding the number of reported cases. In this study, we report the complete genome sequencing of a DENV serotype 4 isolate, genotype II, obtained in the city of Manaus, directly from the serum sample, applying Ion Torrent sequencing technology. The use of a massive sequencing technology allowed the detection of two variable sites, one in the coding region for the viral envelope protein and the other in the nonstructural 1 coding region within viral populations. PMID- 26841046 TI - Association of human papillomavirus and Chlamydia trachomatis with intraepithelial alterations in cervix samples. AB - The influence of different infectious agents and their association with human papillomavirus (HPV) in cervical carcinogenesis have not been completely elucidated. This study describes the association between cytological changes in cervical epithelium and the detection of the most relevant aetiological agents of sexually transmitted diseases. Samples collected from 169 patients were evaluated by conventional cytology followed by molecular analysis to detect HPV DNA, Chlamydia trachomatis, herpes simplex virus 1 and 2,Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, andTreponema pallidum, besides genotyping for most common high-risk HPV. An association between cytological lesions and different behavioural habits such as smoking and sedentariness was observed. Intraepithelial lesions were also associated with HPV and C. trachomatis detection. An association was also found between both simple and multiple genotype infection and cytological changes. The investigation of HPV and C. trachomatisproved its importance and may be considered in the future for including in screening programs, since these factors are linked to the early diagnosis of patients with precursor lesions of cervical cancer. PMID- 26841050 TI - National Development Generates National Identities. AB - The purpose of the article is to test the relationship between national identities and modernisation. We test the hypotheses that not all forms of identity are equally compatible with modernisation as measured by Human Development Index. The less developed societies are characterised by strong ascribed national identities based on birth, territory and religion, but also by strong voluntarist identities based on civic features selected and/or achieved by an individual. While the former decreases with further modernisation, the latter may either decrease or remain at high levels and coexist with instrumental supranational identifications, typical for the most developed countries. The results, which are also confirmed by multilevel regression models, thus demonstrate that increasing modernisation in terms of development contributes to the shifts from classical, especially ascribed, identities towards instrumental identifications. These findings are particularly relevant in the turbulent times increasingly dominated by the hardly predictable effects of the recent mass migrations. PMID- 26841049 TI - Frequency and molecular characterisation of Entamoeba histolytica, Entamoeba dispar, Entamoeba moshkovskii, and Entamoeba hartmanni in the context of water scarcity in northeastern Brazil. AB - This study aimed to estimate the frequency, associated factors, and molecular characterisation of Entamoeba histolytica, Entamoeba dispar, Entamoeba moshkovskii, andEntamoeba hartmanni infections. We performed a survey (n = 213 subjects) to obtain parasitological, sanitation, and sociodemographic data. Faecal samples were processed through flotation and centrifugation methods.E. histolytica, E. dispar, E. moshkovskii, and E. hartmanni were identified by nested-polymerase chain reaction (PCR). The overall prevalence of infection was 22/213 (10.3%). The infection rate among subjects who drink rainwater collected from roofs in tanks was higher than the rate in subjects who drink desalinated water pumped from wells; similarly, the infection rate among subjects who practice open defecation was significantly higher than that of subjects with latrines. Out of the 22 samples positive for morphologically indistinguishableEntamoeba species, the differentiation by PCR was successful for 21. The species distribution was as follows: 57.1% to E. dispar, 23.8% to E. histolytica, 14.3% toE. histolytica and E. dispar, and 4.8% E. dispar and E. hartmanni. These data suggest a high prevalence of asymptomatic infection by the group of morphologically indistinguishable Entamoeba histolytica/dispar/moshkovskiicomplex and E. hartmanni species. In this context of water scarcity, the sanitary and socioenvironmental characteristics of the region appear to favour transmission. PMID- 26841051 TI - Biochemometrics for Natural Products Research: Comparison of Data Analysis Approaches and Application to Identification of Bioactive Compounds. AB - A central challenge of natural products research is assigning bioactive compounds from complex mixtures. The gold standard approach to address this challenge, bioassay-guided fractionation, is often biased toward abundant, rather than bioactive, mixture components. This study evaluated the combination of bioassay guided fractionation with untargeted metabolite profiling to improve active component identification early in the fractionation process. Key to this methodology was statistical modeling of the integrated biological and chemical data sets (biochemometric analysis). Three data analysis approaches for biochemometric analysis were compared, namely, partial least-squares loading vectors, S-plots, and the selectivity ratio. Extracts from the endophytic fungi Alternaria sp. and Pyrenochaeta sp. with antimicrobial activity against Staphylococcus aureus served as test cases. Biochemometric analysis incorporating the selectivity ratio performed best in identifying bioactive ions from these extracts early in the fractionation process, yielding altersetin (3, MIC 0.23 MUg/mL) and macrosphelide A (4, MIC 75 MUg/mL) as antibacterial constituents from Alternaria sp. and Pyrenochaeta sp., respectively. This study demonstrates the potential of biochemometrics coupled with bioassay-guided fractionation to identify bioactive mixture components. A benefit of this approach is the ability to integrate multiple stages of fractionation and bioassay data into a single analysis. PMID- 26841053 TI - Correction: A Statistical Model for Estimation of Fish Density Including Correlation in Size, Space, Time and between Species from Research Survey Data. PMID- 26841052 TI - Tunable Band Alignment with Unperturbed Carrier Mobility of On-Surface Synthesized Organic Semiconducting Wires. AB - The tunable properties of molecular materials place them among the favorites for a variety of future generation devices. In addition, to maintain the current trend of miniaturization of those devices, a departure from the present top-down production methods may soon be required and self-assembly appears among the most promising alternatives. On-surface synthesis unites the promises of molecular materials and of self-assembly, with the sturdiness of covalently bonded structures: an ideal scenario for future applications. Following this idea, we report the synthesis of functional extended nanowires by self-assembly. In particular, the products correspond to one-dimensional organic semiconductors. The uniaxial alignment provided by our substrate templates allows us to access with exquisite detail their electronic properties, including the full valence band dispersion, by combining local probes with spatial averaging techniques. We show how, by selectively doping the molecular precursors, the product's energy level alignment can be tuned without compromising the charge carrier's mobility. PMID- 26841054 TI - What is wrong with the regulatory T cells and foetomaternal tolerance in women with recurrent miscarriages? AB - Couples of whom the woman has had a miscarriage have two major concerns: the cause and possible risk of recurrence. Unfortunately, a significant proportion of cases of recurrent miscarriage (RM) remain unexplained despite detailed investigation. Because data suggest that regulatory T cells (Treg) are involved in the maternal acceptance of the allogeneic foetus, RM could possibly be explained by a disturbance of the Treg network. The possible role of Tregs in RM is described in this review, as well as their potential application in diagnostics and therapeutic intervention trials. PMID- 26841055 TI - Kinetics of cesium lead halide perovskite nanoparticle growth; focusing and de focusing of size distribution. AB - In this work we study the kinetics of cesium lead halide perovskite nanoparticle (NP) growth; the focusing and de-focusing of the NP size distribution. Cesium lead halide perovskite NPs are considered to be attractive materials for optoelectronic applications. Understanding the kinetics of the formation of these all-inorganic perovskite NPs is critical for reproducibly and reliably generating large amounts of uniformly sized NPs. Here we investigate different growth durations for CsPbI3 and CsPbBr3 NPs, tracking their growth by high-resolution transmission electron microscopy and size distribution analysis. As a result, we are able to provide a detailed model for the kinetics of their growth. It was observed that the CsPbI3 NPs exhibit focusing of the size distribution in the first 20 seconds of growth, followed by de-focusing over longer growth durations, while the CsPbBr3 NPs show de-focusing of the size distribution starting from the beginning of the growth. The monomer concentration is depleted faster in the case of CsPbBr3 than in the case of CsPbI3, due to faster diffusion of the monomers, which increases the critical radius and results in de-focusing of the population. Accordingly, focusing is not observed within 40 seconds of growth in the case of CsPbBr3. This study provides important knowledge on how to achieve a narrow size distribution of cesium lead halide perovskite NPs when generating large amounts of these promising, highly luminescent NPs. PMID- 26841056 TI - A Bayesian Method for Cluster Detection with Application to Brain and Breast Cancer in Puget Sound. AB - Cluster detection is an important public health endeavor, and in this article, we describe and apply a recently developed Bayesian method. Commonly used approaches are based on so-called scan statistics and suffer from a number of difficulties, which include how to choose a level of significance and how to deal with the possibility of multiple clusters. The basis of our model is to partition the study region into a set of areas that are either "null" or "non-null," the latter corresponding to clusters (excess risk) or anticlusters (reduced risk). We demonstrate the Bayesian method and compare with a popular existing approach, using data on breast, brain, lung, prostate, and colorectal cancer, in the Puget Sound region of Washington State. PMID- 26841057 TI - Sensitivity Analysis Without Assumptions. AB - Unmeasured confounding may undermine the validity of causal inference with observational studies. Sensitivity analysis provides an attractive way to partially circumvent this issue by assessing the potential influence of unmeasured confounding on causal conclusions. However, previous sensitivity analysis approaches often make strong and untestable assumptions such as having an unmeasured confounder that is binary, or having no interaction between the effects of the exposure and the confounder on the outcome, or having only one unmeasured confounder. Without imposing any assumptions on the unmeasured confounder or confounders, we derive a bounding factor and a sharp inequality such that the sensitivity analysis parameters must satisfy the inequality if an unmeasured confounder is to explain away the observed effect estimate or reduce it to a particular level. Our approach is easy to implement and involves only two sensitivity parameters. Surprisingly, our bounding factor, which makes no simplifying assumptions, is no more conservative than a number of previous sensitivity analysis techniques that do make assumptions. Our new bounding factor implies not only the traditional Cornfield conditions that both the relative risk of the exposure on the confounder and that of the confounder on the outcome must satisfy but also a high threshold that the maximum of these relative risks must satisfy. Furthermore, this new bounding factor can be viewed as a measure of the strength of confounding between the exposure and the outcome induced by a confounder. PMID- 26841058 TI - Re: Thyroid Cancer Among Young People in Fukushima. PMID- 26841059 TI - Re: Thyroid Cancer Among Young People in Fukushima. PMID- 26841060 TI - Re: Thyroid Cancer Among Young People in Fukushima. PMID- 26841061 TI - Re: Thyroid Cancer Among Young People in Fukushima. PMID- 26841062 TI - Soil Nitrogen Status Modifies Rice Root Response to Nematode-Bacteria Interactions in the Rhizosphere. AB - It has been hypothesized that faunal activity in the rhizosphere influences root growth via an auxin-dependent pathway. In this study, two methods were used to adjust nematode and bacterial populations within experimental soils. One is "exclusion", where soil mixed with pig manure was placed in two bags with different mesh sizes (1mm and 5MUm diameter), and then surrounded by an outer layer of unamended soil resulting in soil with a greater populations of bacterial feeding nematodes (1mm) and a control treatment (5MUm). The second method is "inoculation", whereby autoclaved soil was inoculated with bacteria (E. coli and Pseudomonas) and Nematodes (Cephalobus and C. elegans). In order to detect the changes in the rice's perception of auxin under different nutrient and auxin conditions in the presence of soil bacterial-feeding nematodes, responses of soil chemistry (NH4+, NO3- and indole acetic acid (IAA)), rice root growth and the expression of an auxin responsive gene GH3-2 were measured. Results showed that, under low soil nutrient conditions (exclusion), low NO3- correlated with increased root branching and IAA correlated with increased root elongation and GH3-2 expression. However, under high soil nutrient conditions (inoculation), a high NH4+ to NO3- ratio promoted an increase in root surface area and there was an additional influence of NH4+ and NO3- on GH3-2 expression. Thus it was concluded that soil bacterial-feeding nematodes influenced soil nutritional status and soil IAA content, promoting root growth via an auxin dependent pathway that was offset by soil nitrogen status. PMID- 26841064 TI - ON THE USE OF THE MAST MODEL IN ASSESSMENT OF TELEMEDICINE: A COMMENT ON EKELAND AND GROTTLAND. PMID- 26841065 TI - Improvement of clinical outcomes in the patients with gallbladder cancer: lessons from periodic comparison in a tertiary referral center. AB - BACKGROUND: Current guidelines for gallbladder cancer (GBC) contain controversies and some reported no survival improvement in GBC during 20 years. This study was designed to explore the chronologic change of survival outcomes in GBC and prognostic factors. METHODS: Clinicopathologic features and survival outcomes were analyzed in 692 consecutive GBC patients who underwent surgery between 1987 and 2014, including 255 treated in Period (P) 1 (1987-2000) and 437 in P2 (2001 2014). RESULTS: The mean age was 63.3 years. Curative resection rate was 59.2% and 5-year survival rate (5-YSR) after curative resection was 67.1%. Comparisons between P1 and P2 showed that mean age, asymptomatic presentation, extended cholecystectomy, curative resection, adjuvant chemotherapy, and tumor <= T2 were significantly higher during P2. The overall 5-YSR after curative surgery was significantly lower in P1. In patients who underwent curative resection, poor prognostic factors included symptomatic presentation, CA 19-9 >37 IU/ml, poor differentiation, tumor >= T3, and lymph nodal involvement. In patients who received non-curative surgery, well- or moderately differentiated tumor and adjuvant chemotherapy provide survival benefit. CONCLUSIONS: Detection of GBC at an early stage and optimal curative surgery may improve survival outcomes in GBC. Chemotherapy provides survival benefit in palliative setting. PMID- 26841066 TI - The Origin of Life in Alkaline Hydrothermal Vents. AB - Over the last 70 years, prebiotic chemists have been very successful in synthesizing the molecules of life, from amino acids to nucleotides. Yet there is strikingly little resemblance between much of this chemistry and the metabolic pathways of cells, in terms of substrates, catalysts, and synthetic pathways. In contrast, alkaline hydrothermal vents offer conditions similar to those harnessed by modern autotrophs, but there has been limited experimental evidence that such conditions could drive prebiotic chemistry. In the Hadean, in the absence of oxygen, alkaline vents are proposed to have acted as electrochemical flow reactors, in which alkaline fluids saturated in H2 mixed with relatively acidic ocean waters rich in CO2, through a labyrinth of interconnected micropores with thin inorganic walls containing catalytic Fe(Ni)S minerals. The difference in pH across these thin barriers produced natural proton gradients with equivalent magnitude and polarity to the proton-motive force required for carbon fixation in extant bacteria and archaea. How such gradients could have powered carbon reduction or energy flux before the advent of organic protocells with genes and proteins is unknown. Work over the last decade suggests several possible hypotheses that are currently being tested in laboratory experiments, field observations, and phylogenetic reconstructions of ancestral metabolism. We analyze the perplexing differences in carbon and energy metabolism in methanogenic archaea and acetogenic bacteria to propose a possible ancestral mechanism of CO2 reduction in alkaline hydrothermal vents. Based on this mechanism, we show that the evolution of active ion pumping could have driven the deep divergence of bacteria and archaea. PMID- 26841067 TI - Clinical Application of an Innovative Multiplex-Fluorescent-Labeled STRs Assay for Prader-Willi Syndrome and Angelman Syndrome. AB - Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurodevelopmental disorders caused by absence of paternally or maternally expressed imprinted genes on chr15q11.2-q13.3. Three mechanisms are known to be involved in the pathogenesis: microdeletions, uniparental disomy (UPD) and imprinting defects. Both disorders are difficult to be definitely diagnosed at early age if no available molecular cytogenetic tests. In this study, we identified 5 AS patients with the maternal deletion and 26 PWS patients with paternal deletion on chr15q11-q13 by using an innovative multiplex fluorescent-labeled short tandem repeats (STRs) assay based on linkage analysis, and validated by the methylation-specific PCR and array comparative genomic hybridization techniques. More interesting, one of these PWS patients was confirmed as maternal uniparental isodisomy by the STR linkage analysis. The phenotypic and genotypic characteristics of these individuals were also presented. Our results indicate that the new linkage analysis is much faster and easier for large-scale screening deletion and uniparental disomy, thus providing a valuable method for early diagnosis of PWS/AS patients, which is critical for genetic diagnosis, management and improvement of prognosis. PMID- 26841068 TI - Twelve tips for successfully implementing logbooks in clinical training. AB - BACKGROUND: Logbooks are widely used to set learning outcomes and to structure and standardize teaching in clinical settings. Experience shows that logbooks are not always optimally employed in clinical training. In this article, we have summarized our own experiences as well as results of studies into twelve tips on how to successfully implement logbooks into clinical settings. METHODS: We conducted both a workshop concerning the importance of logbook training to exchange experiences in teaching practice, organization, didactic knowledge and a literature research to compare our own experiences and add additional aspects. RESULTS: Tips include the process of developing the logbook itself, the change management process, conditions of training and the integration of logbooks into the curriculum. CONCLUSIONS: Logbooks can be a valuable tool for training in clinical settings, especially when multiple sites are involved, when you take our tips into consideration. PMID- 26841071 TI - Topotactic Transformation Route to Monodisperse beta-NaYF4:Ln(3+) Microcrystals with Luminescence Properties. AB - A novel nonorganic wet route for direct synthesis of uniform hexagonal beta NaYF4:Ln(3+) (Ln = Eu, Tb, Ce/Tb, Yb/Er, and Yb/Tm) microcrystals with various morphologies has been developed wherein the intermediate routine cubic-hexagonal (alpha -> beta) phase transfer process was avoided. The morphology can be effectively tuned into hexagonal disc, prism, and novel hierarchical architectures by systematically fine manipulating the Na2CO3/F(-) feeding ratio. It has been found that the routine alpha -> beta phase transfer for NaYF4 was not detected during the growth, while NaY(CO3)F2 emerged in the initial reaction stage and fast transformed into beta-NaYF4 via a novel topotactic transformation behavior. Detailed structural analysis showed that beta-NaYF4 preferred the [001] epitaxial growth direction of NaY(CO3)F2 due to the structural matching of [001]NaY(CO3)F2//[0001]beta-NaYF4. Besides, the potential application of the as prepared products as phosphors is emphasized by demonstrating multicolor emissions including downconversion, upconversion, and energy transfer (Ce-Tb) process by lanthanides doping. PMID- 26841069 TI - Potential Role of Axonal Chemorepellent Slit2 in Modulating Adventitial Inflammation in a Rat Carotid Artery Balloon Injury Model. AB - Leukocyte infiltration of adventitial and perivascular tissues is an early event in the development of vascular remodeling after injury. We investigated whether Slit/Robo-an axonal chemorepellent system in vertebrate and invertebrate development-is activated during the inflammatory phase that follows endothelial denudation. Using the rat carotid artery model of angioplasty, we conducted a time course analysis of mRNAs encoding Slit ligands (Slit2 and Slit3) and Robo receptors (Robo1, Robo2, and Robo4), as well as proinflammatory cell adhesion molecule (CAM) genes. Adventitial inflammatory cells were counted in immunostained arterial sections. E-selectin, vascular CAM-1, and intercellular CAM-1 were upregulated 2-3 hours after injury, followed by infiltration of neutrophils and monocytes as evidenced by real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry. Slit2, Slit3, and Robo genes exhibited no expression changes at 3 hours; however, they were markedly upregulated 1 day after angioplasty. Intercellular CAM-1 expression was reduced by 50%, and the number of adventitial neutrophils decreased by >75% 1 day after angioplasty. Slit2 has been shown to be a potent chemorepelent of leukocytes, endothelial cells, and smooth muscle cells. Thus, we decided to further investigate the localization of Slit2 in injured vessels. Immunohistochemical stainings revealed the presence of Slit2 within the vessel wall and in the perivascular vasa vasorum of naive and injured arteries. Double immunohistochemical analyses showed that infiltrating monocytes expressed Slit2 in the perivascular and adventitial tissues of injured arteries 1 and 3 days postangioplasty. In addition, recombinant full-length Slit2 and Slit2-N/1118, an N-terminal fragment of Slit2, inhibited stromal cell-derived factor 1-mediated migration of circulating rat peripheral blood mononuclear cells. In summary, adventitial activation of CAM genes and neutrophil infiltration preceded upregulation of Slit/Robo genes. Sli2 expression colocalized with infiltrating inflammatory cells in the adventitial layer. This temporospatial association suggests that leukocyte chemorepellent Slit2 may be involved in halting the adventitial accumulation of inflammatory cells in injured vessels. PMID- 26841072 TI - Fully 3D refraction correction dosimetry system. AB - The irradiation of selective regions in a polymer gel dosimeter results in an increase in optical density and refractive index (RI) at those regions. An optical tomography-based dosimeter depends on rayline path through the dosimeter to estimate and reconstruct the dose distribution. The refraction of light passing through a dose region results in artefacts in the reconstructed images. These refraction errors are dependant on the scanning geometry and collection optics. We developed a fully 3D image reconstruction algorithm, algebraic reconstruction technique-refraction correction (ART-rc) that corrects for the refractive index mismatches present in a gel dosimeter scanner not only at the boundary, but also for any rayline refraction due to multiple dose regions inside the dosimeter. In this study, simulation and experimental studies have been carried out to reconstruct a 3D dose volume using 2D CCD measurements taken for various views. The study also focuses on the effectiveness of using different refractive-index matching media surrounding the gel dosimeter. Since the optical density is assumed to be low for a dosimeter, the filtered backprojection is routinely used for reconstruction. We carry out the reconstructions using conventional algebraic reconstruction (ART) and refractive index corrected ART (ART-rc) algorithms. The reconstructions based on FDK algorithm for cone-beam tomography has also been carried out for comparison. Line scanners and point detectors, are used to obtain reconstructions plane by plane. The rays passing through dose region with a RI mismatch does not reach the detector in the same plane depending on the angle of incidence and RI. In the fully 3D scanning setup using 2D array detectors, light rays that undergo refraction are still collected and hence can still be accounted for in the reconstruction algorithm. It is found that, for the central region of the dosimeter, the usable radius using ART-rc algorithm with water as RI matched medium is 71.8%, an increase of 6.4% compared to that achieved using conventional ART algorithm. Smaller diameter dosimeters are scanned with dry air scanning by using a wide-angle lens that collects refracted light. The images reconstructed using cone beam geometry is seen to deteriorate in some planes as those regions are not scanned. Refraction correction is important and needs to be taken in to consideration to achieve quantitatively accurate dose reconstructions. Refraction modeling is crucial in array based scanners as it is not possible to identify refracted rays in the sinogram space. PMID- 26841070 TI - Towards high-resolution 4D flow MRI in the human aorta using kt-GRAPPA and B1+ shimming at 7T. AB - PURPOSE: To evaluate the feasibility of aortic 4D flow magnetic resonance imaging (MRI) at 7T with improved spatial resolution using kt-GRAPPA acceleration while restricting acquisition time and to address radiofrequency (RF) excitation heterogeneities with B1+ shimming. MATERIALS AND METHODS: 4D flow MRI data were obtained in the aorta of eight subjects using a 16-channel transmit/receive coil array at 7T. Flow quantification and acquisition time were compared for a kt GRAPPA accelerated (R = 5) and a standard GRAPPA (R = 2) accelerated protocol. The impact of different dynamic B1+ shimming strategies on flow quantification was investigated. Two kt-GRAPPA accelerated protocols with 1.2 * 1.2 * 1.2 mm(3) and 1.8 * 1.8 * 2.4 mm(3) spatial resolution were compared. RESULTS: Using kt GRAPPA, we achieved a 4.3-fold reduction in net acquisition time resulting in scan times of about 10 minutes. No significant effect on flow quantification was observed compared to standard GRAPPA with R = 2. Optimizing the B1+ fields for the aorta impacted significantly (P < 0.05) the flow quantification while specific B1+ settings were required for respiration navigators. The high resolution protocol yielded similar flow quantification, but allowed the depiction of branching vessels. CONCLUSION: 7T in combination with B1+ shimming allows for high-resolution 4D flow MRI acquisitions in the human aorta, while kt GRAPPA limits total scan times without affecting flow quantification. J. Magn. Reson. Imaging 2016;44:486-499. PMID- 26841073 TI - 15-Year prognostic utility of coronary artery calcium scoring for all-cause mortality in the elderly. AB - INTRODUCTION: Prior studies have demonstrated a decline in the predictive ability of conventional risk factors (RF) with advancing age, emphasizing the need for novel tools to improve risk stratification in the elderly. Coronary artery calcification (CAC) is a robust predictor of adverse cardiovascular events, but its long-term prognostic utility beyond RFs in elderly persons is unknown. METHODS: A consecutive series of 9715 individuals underwent CAC scoring and were followed for a mean of 14.6 +/- 1.1 years. Multivariable Cox proportional hazards regression (HR) with 95% confidence intervals (95% CI) was employed to assess the independent relationship of CAC and RFs with all-cause death. The incremental value of CAC, stratified by age, was examined by using an area under the receiver operator characteristic curve (AUC) and category-free net reclassification improvement (NRI). RESULTS: Of the overall study sample, 728 (7.5%) adults (mean age 74.2 +/- 4.2 years; 55.6% female) were 70 years or older, of which 157 (21.6%) died. The presence of any CAC was associated with a >4-fold (95% CI = 2.84-6.59) adjusted risk of death for those over the age of 70, which was higher compared with younger study counterparts, or other measured RFs. For individuals 70 years or older, the discriminatory ability of CAC improved upon that of RFs alone (C statistics 0.764 vs. 0.675, P < 0.001). CAC also enabled improved reclassification (category-free NRI = 84%, P < 0.001) when added to RFs. CONCLUSION: In a large-scale observational cohort registry, CAC improves prediction, discrimination, and reclassification of elderly individuals at risk for future death. PMID- 26841076 TI - Kinetics of Hydrogen Radical Reactions with Toluene Including Chemical Activation Theory Employing System-Specific Quantum RRK Theory Calibrated by Variational Transition State Theory. AB - Pressure-dependent reactions are ubiquitous in combustion and atmospheric chemistry. We employ a new calibration procedure for quantum Rice-Ramsperger Kassel (QRRK) unimolecular rate theory within a chemical activation mechanism to calculate the pressure-falloff effect of a radical association with an aromatic ring. The new theoretical framework is applied to the reaction of H with toluene, which is a prototypical reaction in the combustion chemistry of aromatic hydrocarbons present in most fuels. Both the hydrogen abstraction reactions and the hydrogen addition reactions are calculated. Our system-specific (SS) QRRK approach is adjusted with SS parameters to agree with multistructural canonical variational transition state theory with multidimensional tunneling (MS-CVT/SCT) at the high-pressure limit. The new method avoids the need for the usual empirical estimations of the QRRK parameters, and it eliminates the need for variational transition state theory calculations as a function of energy, although in this first application we do validate the falloff curves by comparing SS-QRRK results without tunneling to multistructural microcanonical variational transition state theory (MS-MUVT) rate constants without tunneling. At low temperatures, the two approaches agree well with each other, but at high temperatures, SS-QRRK tends to overestimate falloff slightly. We also show that the variational effect is important in computing the energy-resolved rate constants. Multiple-structure anharmonicity, torsional-potential anharmonicity, and high-frequency-mode vibrational anharmonicity are all included in the rate computations, and torsional anharmonicity effects on the density of states are investigated. Branching fractions, which are both temperature- and pressure dependent (and for which only limited data is available from experiment), are predicted as a function of pressure. PMID- 26841074 TI - Coronary artery Calcium predicts Cardiovascular events in participants with a low lifetime risk of Cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA). AB - AIMS: Patients with a low lifetime risk of coronary heart disease (CHD) are not completely free of events over 10 years. We evaluated predictors for CHD among "low lifetime risk" participants in the population-based Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: MESA enrolled 6814 men and women aged 45-84 years who were free of baseline cardiovascular disease. Using established criteria of non-diabetic, non-smokers with total cholesterol <= 200 mg/dL, systolic BP <= 139 mmHg, and diastolic BP <= 89 mmHg at baseline, we identified 1391 participants with a low lifetime risk for cardiovascular disease. Baseline covariates were age, gender, ethnicity, HDL-C, C-reactive protein, family history of CHD, carotid intima-media thickness and coronary artery calcium (CAC). We calculated event rates and the number needed to scan (NNS) to identify one participant with CAC>0 and > 100. RESULTS: Over 10.4 years median follow-up, there were 33 events (2.4%) in participants with low lifetime risk. There were 479 participants (34%) with CAC>0 including 183 (13%) with CAC>100. CAC was present in 25 (76%) participants who experienced an event. In multivariable analyses, only CAC>100 remained predictive of CHD (HR 4.6; 95% CI: 1.6-13.6; p = 0.005). The event rates for CAC = 0, CAC>0 and CAC>100 were 0.9/1,000, 5.7/1,000, and 11.0/1000 person-years, respectively. The NNS to identify one participant with CAC>0 and > 100 were 3 and 7.6, respectively. CONCLUSIONS: While 10-year event rates were low in those with low lifetime risk, CAC was the strongest predictor of incident CHD. Identification of individuals with CAC = 0 and CAC>100 carries significant potential therapeutic implications. PMID- 26841075 TI - A rare indication for lung transplantation - pulmonary alveolar microlithiasis: institutional experience of five consecutive cases. AB - BACKGROUND: Pulmonary alveolar microlithiasis (PAM) is a rare lung disease caused by calcifications within the alveolar space. The only known effective treatment for an end-stage PAM is lung transplantation (LuTX). METHODS: We performed a retrospective chart review of all individuals that underwent lung transplantation at our center between 1989 and 2013. Five consecutive patients with PAM were identified. RESULTS: Four females and one male with a mean age of 46.3 yr were identified. Extracorporeal membrane oxygenation (ECMO) support was required intraoperatively in four cases and post-operatively in one case. Mean post operative intubation time was 3.3 (range, 2-5) d and mean intensive care unit (ICU) stay was 8.3 (range, 4-12) d. No intraoperative complications were observed. One early patient (operated in 1995) underwent acute re-transplantation on the second post-operative day (POD) and died from sepsis on the 11 POD. In one patient reperfusion edema was observed requiring a prolonged weaning process. No other severe perioperative complications were observed. Four of five patients are currently still alive with normal follow-up parameters. No recurrence of PAM was observed. CONCLUSIONS: Lung transplantation is a feasible therapy option in patients with end-stage PAM showing good post-operative results comparable to other indications for LuTX. PMID- 26841077 TI - Regioselective Synthesis of Carbonyl-Containing Alkyl Chlorides via Silver Catalyzed Ring-Opening Chlorination of Cycloalkanols. AB - A novel and regioselective approach to carbonyl-containing alkyl chlorides via silver-catalyzed ring-opening chlorination of cycloalkanols is reported. Concurrent C(sp(3))-C(sp(3)) bond cleavage and C(sp(3))-Cl bond formation efficiently occur with good yields under mild conditions, and the chlorinated products are readily transformed into other useful synthetic intermediates and drugs. The reaction features complete regioselectivity, high efficiency, and excellent practicality. PMID- 26841078 TI - Multimedia training support for anaesthetists. PMID- 26841079 TI - Constituents from Polygonatum sibiricum and their inhibitions on the formation of advanced glycosylation end products. AB - A new saponin, isonarthogenin 3-O-beta-d-glucopyranosyl-(1->4)-beta-d galactopyranoside (1), together with twelve known compounds, were isolated from the rhizomes of Polygonatum sibiricum. The structures of these compounds were elucidated by analysis of their 1D/2D NMR and MS data. Among them, phenol compounds 4-7 and 9-10 showed significant inhibitions against the formation of advanced glycosylation end products, with IC50 values of 0.091 +/- 0.0021, 0.10 +/- 0.041, 0.014 +/- 0.0027, 0.11 +/- 0.011, 0.13 +/- 0.045, and 0.055 +/- 0.019 MUM, respectively. The results will promote exploiting potential medicinal use of these compounds in the prevention of diabetic complications and supporting Polygonatum sibiricum as a functional food for healthy and medicinal diet. PMID- 26841081 TI - Magnetic-Assisted Noncontact Triboelectric Nanogenerator Converting Mechanical Energy into Electricity and Light Emissions. AB - A magnetic-assisted noncontact triboelectric nanogenerator (TENG) is developed by combining a magnetic responsive layer with a TENG. The novel TENG device is applied to harvest mechanical energy which can be converted into electricity and light emissions. This work has potential for energy harvesting, magnetic sensors, self-powered electronics and optoelectronics applications. PMID- 26841063 TI - The external globus pallidus: progress and perspectives. AB - The external globus pallidus (GPe) of the basal ganglia is in a unique and powerful position to influence processing of motor information by virtue of its widespread projections to all basal ganglia nuclei. Despite the clinical importance of the GPe in common motor disorders such as Parkinson's disease, there is only limited information about its cellular composition and organizational principles. In this review, recent advances in the understanding of the diversity in the molecular profile, anatomy, physiology and corresponding behaviour during movement of GPe neurons are described. Importantly, this study attempts to build consensus and highlight commonalities of the cellular classification based on existing but contentious literature. Additionally, an analysis of the literature concerning the intricate reciprocal loops formed between the GPe and major synaptic partners, including both the striatum and the subthalamic nucleus, is provided. In conclusion, the GPe has emerged as a crucial node in the basal ganglia macrocircuit. While subtleties in the cellular makeup and synaptic connection of the GPe create new challenges, modern research tools have shown promise in untangling such complexity, and will provide better understanding of the roles of the GPe in encoding movements and their associated pathologies. PMID- 26841082 TI - Changes in physical and gelling properties of freeze-dried egg white as a result of temperature and relative humidity. AB - BACKGROUND: The quality of dried egg white with respect to functional properties can be affected by storage conditions. The effect of temperature and relative humidity (RH) on changes in colour and gelling properties in freeze-dried egg white (FDEW) during storage was investigated. RESULTS: The glass transition temperature (Tg ) of FDEW decreased with increasing % RH. The colour of FDEW stored at 60 degrees C was darker yellow than those at 40 and 25 degrees C, particularly at high % RH. RH had no effect on hardness and water-holding capacity (WHC) of gels made from FDEW stored at 25 degrees C for 1 week. However, hardness and WHC of gels from FDEW stored at higher temperatures; 40 degrees C, 48% RH and 60 degrees C, 11% RH dramatically increased. These results related to the differential scanning calorimeter thermograms which showed a broadening peak with lower enthalpy of protein denaturation. Moreover, the protein's SDS-PAGE pattern in the samples stored at high temperatures or RH levels showed protein aggregation. CONCLUSION: Storage of FDEW at high temperature and RH levels induced protein conformation changes. These have contributed to protein aggregation which affected the gelling properties of FDEW. (c) 2016 Society of Chemical Industry. PMID- 26841080 TI - Additive CHARMM force field for naturally occurring modified ribonucleotides. AB - More than 100 naturally occurring modified nucleotides have been found in RNA molecules, in particular in tRNAs. We have determined molecular mechanics force field parameters compatible with the CHARMM36 all-atom additive force field for all these modifications using the CHARMM force field parametrization strategy. Emphasis was placed on fine tuning of the partial atomic charges and torsion angle parameters. Quantum mechanics calculations on model compounds provided the initial set of target data, and extensive molecular dynamics simulations of nucleotides and oligonucleotides in aqueous solutions were used for further refinement against experimental data. The presented parameters will allow for computational studies of a wide range of RNAs containing modified nucleotides, including the ribosome and transfer RNAs. PMID- 26841083 TI - Transnitrosylation products of the dipeptide cysteinyl-cysteine: an examination by tandem mass spectrometry and density functional theory. AB - The fragmentation pathways of protonated mono- and di-nitrosylated derivatives from the dipeptide Cys-Cys obtained by electrospray were examined. Protonated mononitrosylated dipeptide upon loss of NO formed a radical cation, which in turn shows two fragment ions, one from the loss of HS and the other from a neutral loss giving a radical cation of formula C2H5NS(+). Protonated dinitrosylated dipeptide dissociated by losing both NO molecules, forming a cyclic structure with a vicinal disulfide bridge whose major dissociation channel was the loss of CO. After CO loss, two pathways were observed (loss of NH3 and C2H3NS) which were preceded by proton exchange occurring between one beta-carbon and the nitrogen atom. DFT calculations did not show significant differences in the energies involved for the loss of the NO radical from either of the cysteine residues of the protonated di-nitrosylated dipeptide. Upon loss of the first NO radical, the thiyl radical afforded the vicinal disulfide product with a small barrier through radical substitution of the remaining NO moiety. The calculated relative energy barriers for the different channels are in good agreement with experimental observations. Structures of the ions obtained after dissociation are suggested on the basis of the proposed mechanisms. PMID- 26841084 TI - Indication of Mild Hemolytic Reaction Among Preterm Infants With ABO Incompatibility. AB - BACKGROUND: Among term infants, ABO incompatibility is a leading cause of hemolytic disease and neonatal jaundice. With respect to preterm infants, data are lacking. OBJECTIVE: To evaluate the incidence and severity of ABO incompatibility hemolytic disease among preterm infants with respect to hemolytic and jaundice parameters. DESIGN: Clinical and laboratory data were collected retrospectively from the medical records of 118 ABO-incompatible preterms born at gestational age (GA) 29-34 weeks, as well as 118 controls matched for GA, birth weight, and multiplicity. All infants were born at the Sheba Medical Center Tel Hashomer between 2009 and 2012. RESULTS: The study and control groups were similar on all maternal and neonatal outcome parameters. No differences between the groups were recorded throughout hospitalization regarding hematocrit levels or the need for blood transfusion. Bilirubin levels were higher among the study (ABO-incompatible) group during the first 10 days of life; however, no significant differences were found regarding the need for phototherapy. Upon evaluating subgroups divided by GA, we found no differences on any hematological and jaundice factors among preterms of 29-31 weeks, whereas among preterms of 32 34 weeks higher positive direct antiglobulin test (DAT) results (7% vs. 0% in the control, P = 0.014) as well as higher bilirubin levels were documented. CONCLUSIONS: Among ABO-incompatible preterm infants with GA 29-34 weeks, there is no evidence of significant hemolytic reaction derived from placental transfer of antibodies. With increasing GA, antibody transfer becomes more significant, resulting in more positive DAT results and greater incidence of neonatal jaundice. PMID- 26841087 TI - Robust Thick Polymer Brushes Grafted from Gold Surfaces Using Bidentate Thiol Based Atom-Transfer Radical Polymerization Initiators. AB - A new bromoisobutyrate-terminated alkanethiol, 16-(3,5 bis(mercaptomethyl)phenoxy)hexadecyl 2-bromo-2-methylpropanoate (BMTBM), was designed as a bidentate adsorbate to form thermally stable bromoisobutyrate terminated self-assembled monolayers (SAMs) on flat gold surfaces to conduct atom transfer radical polymerizations (ATRPs). The monolayers derived from BMTBM were characterized by ellipsometry, X-ray photoelectron spectroscopy (XPS), and polarization modulation infrared reflection-absorption spectroscopy (PM-IRRAS) and compared to the monolayers formed from 16-mercaptohexadecyl 2-bromo-2 methylpropanoate (MBM), 16-(3-(mercaptomethyl)phenoxy)hexadecyl 2-bromo-2-methyl propanoate (MTBM), and octadecanethiol (C18SH). In this study, although the monolayer derived from BMTBM was less densely packed than those derived from MBM and MTBM, the bidentate adsorbates demonstrated much higher thermal stability in solution-phase thermal desorption tests, owing to the "chelate effect". The enhanced stability of the BMTBM SAMs ensured the development of thick brushes of poly(methyl methacrylate) and polystyrene at elevated temperatures (60, 90, 105, and 120 degrees C). In contrast, SAMs derived from MBM and MTBM failed to grow polymer brushes at temperatures above 100 degrees C. PMID- 26841086 TI - A Worldwide Epidemic: The Problem and Challenges of Preterm Birth in Low- and Middle-Income Countries. AB - Preterm birth (PTB) is the most common cause of neonatal death worldwide and the second leading cause of under-5 mortality. Low- and middle-income countries (LMICs) bear a disproportionate burden of this disease. An estimated 1 million preterm infants die in the neonatal period each year and many of those who survive face lifelong disability. In this review, we explore the global burden of PTB through an examination of risk factors and predisposing clinical conditions found in LMICs. We then discuss current interventions available to prevent PTB and/or mitigate its clinical sequelae. A major finding of this review is that although the majority of the global PTB disease burden is shouldered by LMICs, very little of the research evidence for its prevention and treatment derives from these settings. Primary research and implementation studies that involve LMIC populations are urgently needed. PMID- 26841085 TI - Persistent Effect of Vitamin D Supplementation on Musculoskeletal Parameters in Adolescents One Year After Trial Completion. AB - We showed a beneficial effect of vitamin D supplementation on musculoskeletal parameters in adolescent girls in a 1-year, randomized, double-blinded placebo controlled trial (RCT). Our objective for this study was to investigate the residual effect of vitamin D supplementation on bone mineral content (BMC), bone mineral density (BMD), at the lumbar spine and hip, lean mass, and height, 1 year after trial completion. We performed post hoc analyses in 167 adolescents, 86 girls and 81 boys, age 13.9 +/- 2 years, who received vitamin D or placebo during the trial, and continued into the follow-up trial. Musculoskeletal parameters were measured at baseline, 12 months (intervention), and 24 months (follow-up). ANOVA and t tests were used to compare results between the placebo group and the merged vitamin D arms (200 or 2000 IU/day), by gender. Baseline characteristics were comparable between treatment groups at entry into the extension. Girls who had received vitamin D during the trial, had significantly larger hip BMC increments compared to those assigned to placebo, at 24 months compared to study entry, but not 24 compared to 12 months, which persisted in adjusted analyses. There were no significant differences in bone mass changes between treatment groups in boys, at 24 months compared to 12 months or to baseline. The beneficial effect of vitamin D supplementation on hip bone mass, achieved in girls during the trial, persisted 1 year after trial completion. These net cumulative increments, 1 year after discontinuation of supplementation, may have important implications on optimizing peak bone mass accretion in adolescent girls. (c) 2016 American Society for Bone and Mineral Research. PMID- 26841088 TI - Anomalous Freezing of Nano-Confined Water in Room-Temperature Ionic Liquid 1 Butyl-3-Methylimidazolium Nitrate. AB - Non-crystal formation of ice is investigated by simultaneous X-ray diffraction and differential scanning calorimetry measurements upon cooling to -100 degrees C. At room temperature, size-tunable water confinement (~20 A size) in a room temperature ionic liquid (RTIL, 1-butyl-3-methylimidazolium nitrate, [C4 mim][NO3 ]) exists in a water-rich region (70-90 mol % D2 O). The confined water (water pocket) is characterized by almost monodispersive size distribution. In [C4 mim][NO3 ]-x mol % D2 O (700.75. Hierarchical clustering indicated that there were two main groups of MS patients, those with increased levels of inflammatory response proteins and decreased levels of proteins involved in neuronal tissue development (n = 30), and those with normal protein levels for both of these protein groups (n = 7). The main subgroup of controls clustering with the MS patients showing increased inflammation and decreased neuronal tissue development were patients suffering from chronic fatigue. Our data indicate that the preferable way to quantify proteins in CSF is to first match the samples on total protein amount and then normalize the data based on the median intensities, preferably from the CNS enriched proteins. PMID- 26841091 TI - Everything is connected: social determinants of pediatric health and disease. AB - Carine Tarazi, MA, is an Assistant Editor for Pediatric Research in Boston, Massachusetts, USA. Margie Skeer, ScD, MPH, MSW, served as a Guest Editor for this special issue. Dr. Skeer is Assistant Professor of Public Health and Community Medicine at Tufts University. Her research focuses on adolescent substance misuse and sexual risk prevention, both from epidemiologic and intervention-development perspectives. Kevin Fiscella, MD, MPH, served as a Guest Editor for this special issue. Dr. Fiscella is Tenured Professor of Family Medicine, Public Health Sciences and Community Health at the University of Rochester Medical Center. Dr. Fiscella's research focuses on health and health care disparities, particularly practical strategies to improve health equity. Stephanie Dean, MBA, is Managing Editor of Pediatric Research and is based out of editorial office in The Woodlands, Texas. Olaf Dammann, MD, served as a Guest Editor for this special issue. Dr. Dammann is a Professor of Public Health and Community Medicine, Pediatrics, and Ophthalmology at Tufts University School of Medicine in Boston, Massachusetts, USA, as well as Professor of Perinatal Neuroepidemiology at Hannover Medical School, Hannover, Germany. His research interests include the elucidation of risk factors for brain damage and retinopathy in preterm newborns, the theory of risk and causation in biomedical and public health research, and the development of computational chronic disease models. PMID- 26841089 TI - The Effect of Clinical Chorioamnionitis on Cesarean Delivery in the United States. AB - OBJECTIVE: To examine the association of clinical chorioamnionitis on cesarean delivery in a national sample of hospital discharges. DATA SOURCE: Hospital discharge data from the 1998-2010 Nationwide Inpatient Sample. STUDY DESIGN: We performed a cross-sectional study and general linear modeling was used to determine the association of clinical chorioamnionitis on risk of cesarean delivery. PRINCIPAL FINDINGS: A total of 10,843,682 deliveries and 51,799,431 nationally weighted deliveries were identified. Clinical chorioamnionitis was present in 2.9 percent of cesarean and 1.3 percent of vaginal deliveries (p < .001). In multivariate analysis, clinical chorioamnionitis was associated with a 1.39-fold increased risk of cesarean delivery. Compared with women without clinical chorioamnionitis at an urban/teaching hospital, women with clinical chorioamnionitis at an urban/teaching, urban/nonteaching, and rural hospital were 1.4-1.5 times more likely to have cesarean delivery. Compared with women without clinical chorioamnionitis in the Midwest, the relative risk for cesarean in women with clinical chorioamnionitis was 1.54 for women in the South, 1.47 in the Northeast, 1.39 in the Midwest, and 1.34 in the West. CONCLUSIONS: Women with clinical chorioamnionitis were more likely to have cesarean delivery than those without clinical chorioamnionitis, and the risk of cesarean delivery varied significantly by hospital location, teaching status, and U.S. region. PMID- 26841092 TI - Eosinophilic enteritis due to cow's milk allergy: Possible cause of anastomosis failure following repair of focal intestinal perforation. AB - Reports of cow's milk allergy (CMA) after neonatal gastrointestinal surgery have recently increased. In recent years it has been suggested that the development of CMA after gastrointestinal surgery in newborn infants is due to an immune function. In addition, the development of CMA might be synergistically exacerbated by congenital abnormalities of the intestinal mucosa, general conditional changes and local damage to the intestine by invasive surgery, and poor pre- or post-surgical nutrition. CMA manifests as a variety of symptoms, such as mild vomiting and bloody stool, decreased activity, poor oral intake, and ileus. CMA may also rarely cause gastrointestinal perforation. Here, we report the case of a newborn infant who developed CMA following repair of focal small intestinal perforation, in which eosinophilic enteritis was suspected to be a possible cause of anastomosis leakage. PMID- 26841093 TI - Culturally Embedded Risk Factors for Cambodian Husband-Wife HIV Transmission: From Women's Point of View. AB - PURPOSE: The purpose of this study was to use interview data to examine the validity of a recently published theoretical model of HIV transmission between husband and virginal wives in rural Cambodia. DESIGN: This study used a qualitative description method with a sample of women diagnosed with HIV/AIDS in Phnom Penh, Cambodia. METHODS: Data were collected through in-depth interviews conducted with 15 women who self-identified as having contracted HIV from their HIV-positive husbands. Interviews were conducted in Khmer, translated and back translated for accuracy, and then coded using deductive content analysis. Trustworthiness of study results was protected through peer debriefing, coding to consensus, and maintaining an audit trail. FINDINGS: Each conceptual domain of the prior published theoretical model of HIV transmission was validated and further elaborated by current study data: wives' acceptance of their husbands' involvement with commercial sex workers, the common practice of unprotected sex between HIV-infected spouses and uninfected wives, and wives' beliefs about the value of the ideal Khmer woman. In addition, the current study findings identified a new domain that substantially distinguished between the beliefs and attitudes held about marriage and sex by wives and spouses. CONCLUSIONS: Women were not passive recipients of HIV transmission; they reciprocated with behaviors that were consistent with being a good Khmer woman in rural Cambodia, all of which increased their vulnerability to HIV transmission from their HIV-infected spouses. Future interventions or programs should consider all these factors and not overly rely on simplistic educational messages about wearing barriers for HIV transmission during sex. CLINICAL RELEVANCE: The refined theoretical model of HIV transmission from this qualitative research can be used to formulate culturally sensitive and embedded programs for curbing intramarital HIV transmission in Cambodia among the rural poor. PMID- 26841095 TI - Leptomeningeal metastasis: Clinical experience of 519 cases. AB - BACKGROUND: Diagnosis of leptomeningeal metastasis (LM) has become increasingly common because of enhanced detection via routine use of magnetic resonance imaging (MRI) and longer survival of patients by better systemic control. We investigated clinical features and analyzed potential prognostic factors in a large cohort of patients with LM. METHODS: The clinical features of LM developing from systemic cancers were analyzed retrospectively in patients at the National Cancer Center during 2005-2014. RESULTS: A total of 519 patients were enrolled; 497 had solid, 19 had hematopoietic tumors and 3 had tumors of unknown etiology. Among the solid tumors, the most common primary tumor was lung cancer (334 patients), followed by breast cancer (96) and gastrointestinal cancer (39). Median age at onset was 56 years, and the median Karnofsky performance status (KPS) was 60. Thirty-five percent of patients were diagnosed by MRI alone, 22% by cerebrospinal fluid (CSF) cytology alone, and 42% by both. Treatment included chemotherapy alone in 45%, radiation therapy alone in 10%, and both in 17%; 28% received supportive care alone. Median overall survival was 3 months. KPS >=70, CSF protein level <=50 mg/dl at the diagnosis of LM, and active treatment were associated independently with longer overall survival. Upon subgroup analysis of lung cancer patients, non-small cell lung cancer was a favorable prognostic factor for overall survival. CONCLUSIONS: Despite improved diagnosis via MRI and vigorous therapy, most patients with LM had poor outcomes. However, patients with a high KPS or normal CSF protein levels had favorable prognoses upon active treatment. PMID- 26841094 TI - Macrocytosis as a potential parameter associated with survival after tyrosine kinase inhibitor treatment. AB - AIM OF THE STUDY: As a rise in mean corpuscular volume (MCV) of the erythrocyte is frequently seen during treatment with imatinib and sunitinib, we investigated whether macrocytosis (MCV > 100 fl) also occurs as a class effect in other tyrosine kinase inhibitors (TKIs) and whether occurrence of macrocytosis is associated with outcome. MATERIALS AND METHODS: In 533 patients, using 5 TKIs, we investigated if macrocytosis and an increase in MCV were associated with progression-free survival and overall survival (OS) in specific tumour-treatment combinations. RESULTS: Macrocytosis as well as an increase in MCV from baseline of >10 fl (DeltaMCV +10 fl), when included as a time-dependent covariate, were associated with improved OS in patients with renal cell cancer (RCC) treated with sunitinib (macrocytosis, hazard ratio [HR] = 0.61, p = 0.031, and DeltaMCV +10 fl, HR = 0.58, p = 0.016). CONCLUSION: In sunitinib-treated patients with RCC, the occurrence of macrocytosis, or a substantial increase in MCV levels after start of treatment, could potentially serve as a positive prognostic factor for survival, if validated prospectively. PMID- 26841097 TI - Superfertility is more prevalent in obese women with recurrent early pregnancy miscarriage. PMID- 26841096 TI - Quantitative assessment of the effects of water proton concentration and water T1 changes on amide proton transfer (APT) and nuclear overhauser enhancement (NOE) MRI: The origin of the APT imaging signal in brain tumor. AB - PURPOSE: To quantify pure chemical exchange-dependent saturation transfer (CEST) related amide proton transfer (APT) and nuclear Overhauser enhancement (NOE) signals in a rat glioma model and to investigate the mixed effects of water content and water T1 on APT and NOE imaging signals. METHODS: Eleven U87 tumor bearing rats were scanned at 4.7 T. A relatively accurate mathematical approach, based on extrapolated semisolid magnetization-transfer reference signals, was used to remove the concurrent effects of direct water saturation and semisolid magnetization-transfer. Pure APT and NOE signals, in addition to the commonly used magnetization-transfer-ratio asymmetry at 3.5 ppm, MTRasym (3.5ppm), were assessed. RESULTS: The measured APT signal intensity of the tumor (11.06%, much larger than the value reported in the literature) was the major contributor (approximately 80.6%) to the MTRasym (3.5ppm) contrast between the tumor and the contralateral brain region. Both the water content ([water proton]) and water T1 (T1w ) were increased in the tumor, but there were no significant correlations among APT, NOE, or MTRasym (3.5ppm) signals and T1w /[water proton]. CONCLUSION: The effect of increasing T1w on the CEST signal in the tumor was mostly eliminated by the effect of increasing water content, and the observed APT weighted hyperintensity in the tumor should be dominated by the increased amide proton concentration. Magn Reson Med 77:855-863, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26841098 TI - Simultaneous Photoelectrochemical Immunoassay of Dual Cardiac Markers Using Specific Enzyme Tags: A Proof of Principle for Multiplexed Bioanalysis. AB - In this Letter, on the basis of the CdS quantum dots functionalized TiO2 nanotubes electrode, we proposed a simultaneous photoelectrochemical (PEC) immunoassay of dual cardiac markers using specific enzyme tags of alkaline phosphatase (ALP) and acetylcholine esterase (AChE). ALP and AChE were integrated into the PEC system through the sandwich immunobinding and could specifically catalyze the hydrolysis of ascorbic acid 2-phosphate (AAP) or the acetylthiocholine (ATC) to in situ generate ascorbic acid (AA) or thiocholine (TC) for sacrificial electron donating. These two enzymes were thus used to differentiate the signals of two cardiac targets in connection with the sandwich immunorecognition and PEC responses to the corresponding electron donors. This strategy demonstrates a proof of principle for the successful integration of dual enzyme tags with PEC immunoassay that can potentially provide a general format for multiplexed PEC bioanalysis. PMID- 26841099 TI - Relationship between Histological and Clinical Course of Psoriasis: A Pilot Investigation by Reflectance Confocal Microscopy during Goeckerman Treatment. AB - Alterations of the skin microvasculature are known to play an important role in the development and maintenance of psoriatic skin lesions. In this study, we investigated lesional skin in 11 psoriatic patients during a modified Goeckerman treatment using reflectance confocal microscopy (RCM) to study the relationship between clinical clearance and histological normalization of psoriatic skin and the significance of histological abnormalities on the course of disease. The treatment regimen resulted in a significant reduction of the Psoriasis Area and Severity Index (PASI) as well as capillary and papillary diameters (p < 0.0001). The capillary and papillary diameters were still enlarged when compared to those in normal skin (p < 0.001). Capillary and papillary diameters correlated with each other prior to and after treatment (correlation coefficient = 0.63 and 0.64, p = 0.01 and 0.002, respectively) but not with the PASI. Capillary and papillary diameters after treatment and percentage reduction of the PASI during treatment seemed to be better predictors for the clinical course of relapse than the PASI after treatment. These findings make the subclinical changes of psoriatic skin vessels and dermal papillae a legitimate target for treatment. Further investigations of a large group of patients are needed to evaluate the potential of RCM findings as successor of the PASI in the monitoring of psoriasis. PMID- 26841100 TI - Obesity in pregnancy: not such a new problem. PMID- 26841101 TI - Instrument validation process: a case study using the Paediatric Pain Knowledge and Attitudes Questionnaire. AB - AIMS AND OBJECTIVES: To compare two methods of calculating interrater agreement while determining content validity of the Paediatric Pain Knowledge and Attitudes Questionnaire for use with Australian nurses. BACKGROUND: Paediatric pain assessment and management documentation was found to be suboptimal revealing a need to assess paediatric nurses' knowledge and attitude to pain. The Paediatric Pain Knowledge and Attitudes Questionnaire was selected as it had been reported as valid and reliable in the United Kingdom with student nurses. The questionnaire required content validity determination prior to use in the Australian context. DESIGN: A two phase process of expert review. METHODS: Ten paediatric nurses completed a relevancy rating of all 68 questionnaire items. In phase two, five pain experts reviewed the items of the questionnaire that scored an unacceptable item level content validity. Item and scale level content validity indices and intraclass correlation coefficients were calculated. RESULTS: In phase one, 31 items received an item level content validity index <0.78 and the scale level content validity index average was 0.80 which were below levels required for acceptable validity. The intraclass correlation coefficient was 0.47. In phase two, 10 items were amended and four items deleted. The revised questionnaire provided a scale level content validity index average >0.90 and an intraclass correlation coefficient of 0.94 demonstrating excellent agreement between raters therefore acceptable content validity. CONCLUSION: Equivalent outcomes were achieved using the content validity index and the intraclass correlation coefficient. RELEVANCE TO CLINICAL PRACTICE: To assess content validity the content validity index has the advantage of providing an item level score and is a simple calculation. The intraclass correlation coefficient requires statistical knowledge, or support, and has the advantage of accounting for the possibility of chance agreement. PMID- 26841102 TI - The gap-startle paradigm to assess auditory temporal processing: Bridging animal and human research. AB - The gap-prepulse inhibition of the acoustic startle (GPIAS) paradigm is the primary test used in animal research to identify gap detection thresholds and impairment. When a silent gap is presented shortly before a loud startling stimulus, the startle reflex is inhibited and the extent of inhibition is assumed to reflect detection. Here, we applied the same paradigm in humans. One hundred and fifty-seven normal-hearing participants were tested using one of five gap durations (5, 25, 50, 100, 200 ms) in one of the following two paradigms-gap embedded in or gap-following-the continuous background noise. The duration inhibition relationship was observable for both conditions but followed different patterns. In the gap-embedded paradigm, GPIAS increased significantly with gap duration up to 50 ms and then more slowly up to 200 ms (trend only). In contrast, in the gap-following paradigm, significant inhibition-different from 0--was observable only at gap durations from 50 to 200 ms. The finding that different patterns are found depending on gap position within the background noise is compatible with distinct mechanisms underlying each of the two paradigms. PMID- 26841104 TI - Implicit expectations influence target detection in children and adults. AB - When a sound occurs at a predictable time, it gets processed more efficiently. Predictability of the temporal structure of acoustic inflow has been found to influence the P3b of event-related potentials in young adults, such that highly predictable compared to less predictable input leads to earlier P3b peak latencies. In our study, we wanted to investigate the influence of predictability on target processing indexed by the P3b in children (10-12 years old) and young adults. To do that, we used an oddball paradigm with two conditions of predictability (high and low). In the High-predictability condition, a high pitched target tone occurred most of the time in the fifth position of a five tone pattern (after four low-pitched non-target sounds), whereas in the Low predictability condition, no such rule was implemented. The target tone occurred randomly following 2, 3, 4, 5, or 6 non-target tones. In both age groups, reaction time to predictable targets was faster than to non-predictable targets. Remarkably, this effect was largest in children. Consistent with the behavioral responses, the onset latency of the P3b response elicited by targets in both groups was earlier in the predictable than the unpredictable conditions. However, only the children had significantly earlier peak latency responses for predictable targets. Our results demonstrate that target stimulus predictability increases processing speed in children and adults even when predictability was only implicitly derived by the stimulus statistics. Children did have larger effects of predictability, seeming to benefit more from predictability for target detection. PMID- 26841103 TI - Incremental validity of the episode size criterion in binge-eating definitions: An examination in women with purging syndromes. AB - OBJECTIVE: Of the two primary features of binge eating, loss of control (LOC) eating is well validated while the role of eating episode size is less clear. Given the ICD-11 proposal to eliminate episode size from the binge-eating definition, the present study examined the incremental validity of the size criterion, controlling for LOC. METHOD: Interview and questionnaire data come from four studies of 243 women with bulimia nervosa (n = 141) or purging disorder (n = 102). Hierarchical linear regression tested if the largest reported episode size, coded in kilocalories, explained additional variance in eating disorder features, psychopathology, personality traits, and impairment, holding constant LOC eating frequency, age, and body mass index (BMI). Analyses also tested if episode size moderated the association between LOC eating and these variables. RESULTS: Holding LOC constant, episode size explained significant variance in disinhibition, trait anxiety, and eating disorder-related impairment. Episode size moderated the association of LOC eating with purging frequency and depressive symptoms, such that in the presence of larger eating episodes, LOC eating was more closely associated with these features. Neither episode size nor its interaction with LOC explained additional variance in BMI, hunger, restraint, shape concerns, state anxiety, negative urgency, or global functioning. DISCUSSION: Taken together, results support the incremental validity of the size criterion, in addition to and in combination with LOC eating, for defining binge eating episodes in purging syndromes. Future research should examine the predictive validity of episode size in both purging and nonpurging eating disorders (e.g., binge eating disorder) to inform nosological schemes. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:651-662). PMID- 26841105 TI - Trajectories and Prognosis of Older Patients Who Have Prolonged Mechanical Ventilation After High-Risk Surgery. AB - OBJECTIVES: Surgical patients often receive routine postoperative mechanical ventilation with excellent outcomes. However, older patients who receive prolonged mechanical ventilation may have a significantly different long-term trajectory not fully captured in 30-day postoperative metrics. The objective of this study is to describe patterns of mortality and hospitalization for Medicare beneficiaries 66 years old and older who have major surgery with and without prolonged mechanical ventilation. DESIGN: Retrospective cohort study. SETTING: Hospitals throughout the United States. PATIENTS: Five percent random national sample of elderly Medicare beneficiaries (age >= 66 yr) who underwent 1 of 227 operations previously defined as high risk during an inpatient stay at an acute care hospital between January 1, 2005, and November 30, 2009. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 117,917 episodes for older patients who had high-risk surgery; 4% received prolonged mechanical ventilation during the hospitalization. Patients who received prolonged mechanical ventilation had higher 1-year mortality rate than patients who did not have prolonged ventilation (64% [95% CI, 62-65%] vs 17% [95% CI, 16.4-16.9%]). Thirty day survivors who received prolonged mechanical ventilation had a 1-year mortality rate of 47% (95% CI, 45-48%). Thirty-day survivors who did not receive prolonged ventilation were more likely to be discharged home than patients who received prolonged ventilation 71% versus 10%. Patients who received prolonged ventilation and were not discharged by postoperative day 30 had a substantially increased 1-year mortality (adjusted hazard ratio, 4.39 [95% CI, 3.29-5.85]) compared with patients discharged home by day 30. Hospitalized 30-day survivors who received prolonged mechanical ventilation and died within 6 months of their index procedure spent the majority of their remaining days hospitalized. CONCLUSIONS: Older patients who require prolonged mechanical ventilation after high-risk surgery and survive 30 days have a significant 1-year risk of mortality and high burdens of treatment. This difficult trajectory should be considered in surgical decision making and has important implications for surgeons, intensivists, and patients. PMID- 26841107 TI - Space Use and Movement Patterns in a Semi-Free-Ranging Herd of European Bison (Bison bonasus). AB - The successful reintroduction and restocking of the European Bison demands a reliable knowledge of the biology of this species. Yet little is known to date about the European bison, and empirical data remains insufficient to set up a reliable plan ensuring the reintroduction, maintenance and survival of populations in habitats that have been largely modified by human activity. Studies of the ecology, social behaviour and management of bison are therefore crucial to the conservation of this species and its cohabitation with humans. To meet these challenges, we focused on movement patterns and space use in a semi free-ranging herd of European bison living in the Reserve Biologique des Monts d'Azur (France). Bison spend over 80% of their time foraging and resting; foraging mainly occurs around the artificial feeding sites (i.e., hay racks) or in meadows. The time of day and the presence of snow have no influence on the time budget allocated to each activity. Animals, however, spend more time at the food racks in winter. Bison also spend most of their time in small groups of individuals, confirming the occurrence of both fission-fusion dynamics and sexual segregation in this species. Bison seem to follow a Levy walk pattern of movement, which is probably related to the geographical distribution and size of food patches in the reserve. The conclusions of this study provide a better understanding of the sociality, life habits and habitat use of bison, and also describe how the provision of hay affects all these behaviours. These results could be useful in the development of tools to select the most suitable habitats for the reintroduction, management and conservation of bison populations. PMID- 26841106 TI - Transcriptome and Expression Patterns of Chemosensory Genes in Antennae of the Parasitoid Wasp Chouioia cunea. AB - Chouioia cunea Yang is an endoparasitic wasp that attacks pupae of Hyphantria cunea (Drury), an invasive moth species that severely damages forests in China. Chemosensory systems of insects are used to detect volatile chemical odors such as female sex pheromones and host plant volatiles. The antennae of parasite wasps are important for host detection and other sensory-mediated behaviors. We identified and documented differential expression profiles of chemoreception genes in C. cunea antennae. A total of 25 OBPs, 80 ORs, 10 IRs, 11 CSP, 1 SNMPs, and 17 GRs were annotated from adult male and female C. cunea antennal transcriptomes. The expression profiles of 25 OBPs, 16 ORs, and 17 GRs, 5 CSP, 5 IRs and 1 SNMP were determined by RT-PCR and RT-qPCR for the antenna, head, thorax, and abdomen of male and female C. cunea. A total of 8 OBPs, 14 ORs, and 8 GRs, 1 CSP, 4 IRs and 1 SNMPs were exclusively or primarily expressed in female antennae. These female antennal-specific or dominant expression profiles may assist in locating suitable host and oviposition sites. These genes will provide useful targets for advanced study of their biological functions. PMID- 26841108 TI - Mapping the Relative Probability of Common Toad Occurrence in Terrestrial Lowland Farm Habitat in the United Kingdom. AB - INTRODUCTION: The common toad (Bufo bufo) is of increasing conservation concern in the United Kingdom (UK) due to dramatic population declines occurring in the past century. Many of these population declines coincided with reductions in both terrestrial and aquatic habitat availability and quality and have been primarily attributed to the effect of agricultural land conversion (of natural and semi natural habitats to arable and pasture fields) and pond drainage. However, there is little evidence available to link habitat availability with common toad population declines, especially when examined at a broad landscape scale. Assessing such patterns of population declines at the landscape scale, for instance, require an understanding of how this species uses terrestrial habitat. METHODS: We intensively studied the terrestrial resource selection of a large population of common toads in Oxfordshire, England, UK. Adult common toads were fitted with passive integrated transponder (PIT) tags to allow detection in the terrestrial environment using a portable PIT antenna once toads left the pond and before going into hibernation (April/May-October 2012 and 2013). We developed a population-level resource selection function (RSF) to assess the relative probability of toad occurrence in the terrestrial environment by collecting location data for 90 recaptured toads. RESULTS: The predicted relative probability of toad occurrence for this population was greatest in wooded habitat near to water bodies; relative probability of occurrence declined dramatically > 50 m from these habitats. Toads also tended to select habitat near to their breeding pond and toad occurrence was negatively related to urban environments. PMID- 26841109 TI - Web-based education. PMID- 26841111 TI - Continuing Medical Education for Air Medical Providers: The Successes and Challenges. AB - OBJECTIVE: Research has shown that patients transported by nonpediatric teams have higher rates of morbidity and mortality. There is currently a paucity of pediatric standardized ongoing medical education for emergency medical service providers, thus we aimed to develop a model curriculum to increase their knowledge regarding pediatric respiratory distress and failure. METHODS: The curriculum was based on the Kolb Learning Cycle to optimize learning. Target learners were flight nurses (registered nurse) and emergency medical technicians of a private helicopter emergency transport team. The topics included were pediatric stridor, wheezing, and respiratory failure. Online modules were developed for continued spaced education. Knowledge gained from the interventions was measured by precurricular and postcurricular testing and compared with paired t tests. A linear mixed regression model was used to investigate covariates of interest. RESULTS: Sixty-two learners attended the workshop. Fifty-nine learners completed both precurricular and postcurricular testing. The mean increase between pretest and posttest scores was 12.1% (95% confidence interval, 9.4, 14.8; P < 0.001). Type of licensure (private emergency medical technician vs registered nurse) and number of years experience had no association with the level of knowledge gained. Learners who had greater than 1 year of pediatric transport experience scored higher on their pretests. There was no significant retention shown by those who participated in spaced education. CONCLUSIONS: The curriculum was associated with a short term increased knowledge regarding pediatric respiratory distress and failure for emergency helicopter transport providers and could be used as an alternative model to develop standardized ongoing medical education in pediatrics. Further work is needed to achieve knowledge retention in this learner population. PMID- 26841110 TI - Evidence of Partial Migration in a Large Coastal Predator: Opportunistic Foraging and Reproduction as Key Drivers? AB - Understanding animal movement decisions that involve migration is critical for evaluating population connectivity, and thus persistence. Recent work on sharks has shown that often only a portion of the adult population will undertake migrations, while the rest may be resident in an area for long periods. Defining the extent to which adult sharks use specific habitats and their migratory behaviour is essential for assessing their risk of exposure to threats such as fishing and habitat degradation. The present study used acoustic telemetry to examine residency patterns and migratory behaviour of adult bull sharks (Carcharhinus leucas) along the East coast of Australia. Fifty-six VR2W acoustic receivers were used to monitor the movements of 33 bull sharks in the central Great Barrier Reef (GBR). Both males and females were detected year-round, but their abundance and residency peaked between September and December across years (2012-2014). High individual variability in reef use patterns was apparent, with some individuals leaving the array for long periods, whereas others (36%) exhibited medium (0.20-0.40) or high residency (> 0.50). A large portion of the population (51%) undertook migrations of up to 1,400 km to other coral reefs and/or inshore coastal habitats in Queensland and New South Wales. Most of these individuals (76%) were mature females, and the timing of migrations coincided with the austral summer (Dec-Feb). All migrating individuals (except one) returned to the central GBR, highlighting its importance as a potential foraging ground. Our findings suggest that adult bull sharks appear to be highly dependent on coral reef resources and provide evidence of partial migration, where only a portion of the female population undertook seasonal migrations potentially to give birth. Given that estuarine habitats face constant anthropogenic pressures, understanding partial migration and habitat connectivity of large coastal predators should be a priority for their management. PMID- 26841112 TI - Sex Differences in HIV Prevalence Persist over Time: Evidence from 18 Countries in Sub-Saharan Africa. AB - OBJECTIVE: The aim of this study was to examine changes over time in the female: male HIV prevalence ratio in 18 countries in Sub-Saharan Africa, overall and when stratified by area of residence, educational attainment and marital status. METHODOLOGY: We used data from the Demographic and Health Surveys, which are nationally representative household surveys. By using data from 18 countries with at least two survey rounds with HIV testing, and dividing the countries into three regions (Western/Central, Eastern and Southern) we were able to examine cross-country and regional changes in the female: male HIV prevalence ratio over time. Logistic regression was used to estimate female: male HIV prevalence ratios in urban versus rural areas and for different categories of education and marital status. To assess changes over time, we compared the confidence intervals of the prevalence ratios. RESULTS: The female: male HIV prevalence ratio was above one in all countries in at least one survey round for both ages 15-24 years and 25-49 years. In 13 out of 18 countries the prevalence ratio was higher for the younger age group compared to the age group 25-49 years (3 significant) and this difference in prevalence ratios between the age groups did not change over time. Overall, there was a higher frequency of increasing than decreasing prevalence ratios. The gender disparity was greater among those who were married/living together than among the never-married, and over time, the ratio was more stable among the married/living together. The study found no clear differential changes by education. CONCLUSION: Women continue to carry the greater burden of HIV in Sub-Saharan Africa and there is no clear pattern of change in the gap between men and women as the direction and magnitude of change in the prevalence ratios varied greatly. PMID- 26841113 TI - The Arabidopsis transcriptional regulator DPB3-1 enhances heat stress tolerance without growth retardation in rice. AB - The enhancement of heat stress tolerance in crops is an important challenge for food security to facilitate adaptation to global warming. In Arabidopsis thaliana, the transcriptional regulator DNA polymerase II subunit B3-1 (DPB3 1)/nuclear factor Y subunit C10 (NF-YC10) has been reported as a positive regulator of Dehydration-responsive element binding protein 2A (DREB2A), and the overexpression of DPB3-1 enhances heat stress tolerance without growth retardation. Here, we show that DPB3-1 interacts with DREB2A homologues in rice and soya bean. Transactivation analyses with Arabidopsis and rice mesophyll protoplasts indicate that DPB3-1 and its rice homologue OsDPB3-2 function as positive regulators of DREB2A homologues. Overexpression of DPB3-1 did not affect plant growth or yield in rice under nonstress conditions. Moreover, DPB3-1 overexpressing rice showed enhanced heat stress tolerance. Microarray analysis revealed that many heat stress-inducible genes were up-regulated in DPB3-1 overexpressing rice under heat stress conditions. However, the overexpression of DPB3-1 using a constitutive promoter had almost no effect on the expression of these genes under nonstress conditions. This may be because DPB3-1 is a coactivator and thus lacks inherent transcriptional activity. We conclude that DPB3-1, a coactivator that functions specifically under abiotic stress conditions, could be utilized to increase heat stress tolerance in crops without negative effects on vegetative and reproductive growth. PMID- 26841114 TI - Sex Differences and Correlates of Pain in Patients with Comorbid Obesity and Binge Eating Disorder. AB - Sex differences and correlates of pain were examined in a sample of patients with comorbid binge eating disorder (BED) and obesity. One hundred fifty-two treatment seeking patients with BED completed the Brief Pain Inventory. Analysis of covariance was utilized to compare women and men on pain, and correlational analysis, overall and by sex, was performed to examine relationships among pain, eating behaviour and metabolic risk factors. Women reported significantly greater pain severity and pain interference than men. Among women, eating behaviour and metabolic markers were not associated with pain. Among men, however, binge frequency was significantly associated with pain, as was high-density lipoprotein cholesterol and fasting glucose. In sum, while women in this sample had more pain than men, the presence of pain in men was associated with increased behavioural and metabolic risk factors. Findings have clinical implications for the assessment of comorbid pain and obesity-related health risks among individuals with BED. PMID- 26841116 TI - Long-Life and High-Areal-Capacity Li-S Batteries Enabled by a Light-Weight Polar Host with Intrinsic Polysulfide Adsorption. AB - Lithium-sulfur batteries are attractive electrochemical energy storage systems due to their high theoretical energy density and very high natural abundance of sulfur. However, practically, Li-S batteries suffer from short cycling life and low sulfur utilization, particularly in the case of high-sulfur-loaded cathodes. Here, we report on a light-weight nanoporous graphitic carbon nitride (high surface-area g-C3N4) that enables a sulfur electrode with an ultralow long-term capacity fade rate of 0.04% per cycle over 1500 cycles at a practical C/2 rate. More importantly, it exhibits good high-sulfur-loading areal capacity (up to 3.5 mAh cm(-2)) with stable cell performance. We demonstrate the strong chemical interaction of g-C3N4 with polysulfides using a combination of spectroscopic experimental studies and first-principles calculations. The 53.5% concentration of accessible pyridinic nitrogen polysulfide adsorption sites is shown to be key for the greatly improved cycling performance compared to that of N-doped carbons. PMID- 26841115 TI - Flavonoid Compound Icariin Activates Hypoxia Inducible Factor-1alpha in Chondrocytes and Promotes Articular Cartilage Repair. AB - Articular cartilage has poor capability for repair following trauma or degenerative pathology due to avascular property, low cell density and migratory ability. Discovery of novel therapeutic approaches for articular cartilage repair remains a significant clinical need. Hypoxia is a hallmark for cartilage development and pathology. Hypoxia inducible factor-1alpha (HIF-1alpha) has been identified as a key mediator for chondrocytes to response to fluctuations of oxygen availability during cartilage development or repair. This suggests that HIF-1alpha may serve as a target for modulating chondrocyte functions. In this study, using phenotypic cellular screen assays, we identify that Icariin, an active flavonoid component from Herba Epimedii, activates HIF-1alpha expression in chondrocytes. We performed systemic in vitro and in vivo analysis to determine the roles of Icariin in regulation of chondrogenesis. Our results show that Icariin significantly increases hypoxia responsive element luciferase reporter activity, which is accompanied by increased accumulation and nuclear translocation of HIF-1alpha in murine chondrocytes. The phenotype is associated with inhibiting PHD activity through interaction between Icariin and iron ions. The upregulation of HIF-1alpha mRNA levels in chondrocytes persists during chondrogenic differentiation for 7 and 14 days. Icariin (10-6 M) increases the proliferation of chondrocytes or chondroprogenitors examined by MTT, BrdU incorporation or colony formation assays. Icariin enhances chondrogenic marker expression in a micromass culture including Sox9, collagen type 2 (Col2alpha1) and aggrecan as determined by real-time PCR and promotes extracellular matrix (ECM) synthesis indicated by Alcian blue staining. ELISA assays show dramatically increased production of aggrecan and hydroxyproline in Icariin-treated cultures at day 14 of chondrogenic differentiation as compared with the controls. Meanwhile, the expression of chondrocyte catabolic marker genes including Mmp2, Mmp9, Mmp13, Adamts4 and Adamts5 was downregulated following Icariin treatment for 14 days. In a differentiation assay using bone marrow mesenchymal stem cells (MSCs) carrying HIF-1alpha floxed allele, the promotive effect of Icariin on chondrogenic differentiation is largely decreased following Cre recombinase mediated deletion of HIF-1alpha in MSCs as indicated by Alcian blue staining for proteoglycan synthesis. In an alginate hydrogel 3D culture system, Icariin increases Safranin O positive (SO+) cartilage area. This phenotype is accompanied by upregulation of HIF-1alpha, increased proliferating cell nuclear antigen positive (PCNA+) cell numbers, SOX9+ chondrogenic cell numbers, and Col2 expression in the newly formed cartilage. Coincide with the micromass culture, Icariin treatment upregulates mRNA levels of Sox9, Col2alpha1, aggrecan and Col10alpha1 in the 3D cultures. We then generated alginate hydrogel 3D complexes incorporated with Icariin. The 3D complexes were transplanted in a mouse osteochondral defect model. ICRS II histological scoring at 6 and 12 weeks post transplantation shows that 3D complexes incorporated with Icariin significantly enhance articular cartilage repair with higher scores particularly in selected parameters including SO+ cartilage area, subchondral bone and overall assessment than that of the controls. The results suggest that Icariin may inhibit PHD activity likely through competition for cellular iron ions and therefore it may serve as an HIF-1alpha activator to promote articular cartilage repair through regulating chondrocyte proliferation, differentiation and integration with subchondral bone formation. PMID- 26841117 TI - Phase-Specific Vocalizations of Male Mice at the Initial Encounter during the Courtship Sequence. AB - Mice produce ultrasonic vocalizations featuring a variety of syllables. Vocalizations are observed during social interactions. In particular, males produce numerous syllables during courtship. Previous studies have shown that vocalizations change according to sexual behavior, suggesting that males vary their vocalizations depending on the phase of the courtship sequence. To examine this process, we recorded large sets of mouse vocalizations during male-female interactions and acoustically categorized these sounds into 12 vocal types. We found that males emitted predominantly short syllables during the first minute of interaction, more long syllables in the later phases, and mainly harmonic sounds during mounting. These context- and time-dependent changes in vocalization indicate that vocal communication during courtship in mice consists of at least three stages and imply that each vocalization type has a specific role in a phase of the courtship sequence. Our findings suggest that recording for a sufficiently long time and taking the phase of courtship into consideration could provide more insights into the role of vocalization in mouse courtship behavior in future study. PMID- 26841118 TI - Designing axial growth of Co-Ni bimetallic nanowires with hexagon-like caps and their catalytic hydrogenation for nitrobenzene. AB - Co-Ni bimetal nanocrystals, which are constructed with long wires and hexagon like caps, were synthesized through supersaturation, precipitation, and axial growth from the prenucleated bimetal seeds. These Co-Ni bimetallic nanowires with hexagonal caps are more effective than corresponding nanoparticles for the catalytic hydrogenation of nitrobenzene to produce aniline. PMID- 26841119 TI - Serum Calprotectin Versus Acute-Phase Reactants in the Discrimination of Inflammatory Disease Activity in Rheumatoid Arthritis Patients Receiving Tumor Necrosis Factor Inhibitors. AB - OBJECTIVE: To compare the accuracy of serum calprotectin and acute-phase reactants (C-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) in stratifying disease activity in rheumatoid arthritis (RA) patients receiving tumor necrosis factor inhibitors (TNFi), and to correlate calprotectin levels with TNFi trough serum levels. METHODS: We conducted a cross-sectional study of 87 RA patients receiving adalimumab, etanercept (ETN), or infliximab (IFX); 56 psoriatic arthritis (PsA) patients and 40 healthy blood donors were included as controls. Associations between calprotectin, CRP, and ESR and composite articular indices (Disease Activity Score in 28 joints [DAS28], Simplified Disease Activity Index [SDAI], and Clinical Disease Activity Index) were analyzed by correlation and linear regression and the accuracy and discriminatory capacity of calprotectin by receiver operator characteristic curves (area under the curve [AUC]). RESULTS: Calprotectin levels correlated better with all composite activity indices than CRP and ESR (all r coefficients >0.70). Calprotectin levels were significantly lower in RA and PsA patients in clinical remission compared with those with low disease activity for all articular indices. In RA, ESR discriminated between remission and low disease activity only when using DAS28, and CRP only with SDAI. In RA patients in remission/low disease activity, calprotectin but not CRP or ESR distinguished between patients with no swollen joints and those with >=1 swollen joint (1.74 MUg/ml versus 3.04 MUg/ml; P = 0.010). Using DAS28 >=2.6 as the reference variable, calprotectin showed an AUC of 0.92; the best cutoff was >=2.47 MUg/ml with a likelihood ratio of 6.3 (95% confidence interval 2.5-15.8). Calprotectin serum levels inversely correlated with trough serum drug levels of ETN (rho = -0.671, P < 0.001) and IFX (rho = 0.729, P = 0.017). CONCLUSION: Calprotectin may more accurately discriminate disease activity in RA patients receiving TNFi than acute-phase reactants, even in patients with low inflammatory activity. PMID- 26841121 TI - Atypical Tzanck smear findings in pemphigus vulgaris. PMID- 26841123 TI - Preparing students for the ethical challenges on international health electives: A systematic review of the literature on educational interventions. AB - International health electives pose specific ethical challenges for students travelling from to low and middle income countries. We undertook a systematic review of the literature on interventions to prepare students to identify ethical issues addressed, educational approaches and to collate evidence on the effectiveness of different strategies. We searched nine electronic databases of peer-reviewed literature and identified grey literature through key word searches; supplemented through citation mapping and expert consultation. Articles that described ethical training conducted by universities or professional bodies were included for review. We reviewed forty-four full text articles. Ten sources of published literature and seven sources of grey literature met our inclusion criteria. We identified thirteen ethical situations that students should be prepared to manage and eight generic skills to support this process. Most interventions were delivered before the elective, used case studies or guidelines. Some suggested ethical principles or a framework for analysis of ethical issues. Only two papers evaluated the intervention described. Our paper collates a small but growing body of work on education to prepare students to manage ethical issues. Ethical training should have elements that are delivered before, during and after the elective. Interventions should include case studies covering thirteen ethical issues identified here, linked to ethical principles and a process for responding to ethical issues. We suggest that evaluations of interventions are an important area for future research. PMID- 26841120 TI - Over-Expression of CD200 Protects Mice from Dextran Sodium Sulfate Induced Colitis. AB - BACKGROUND AND AIM: CD200:CD200 receptor (CD200R) interactions lead to potent immunosuppression and inhibition of autoimmune inflammation. We investigated the effect of "knockout"of CD200 or CD200R, or over-expression of CD200, on susceptibility to dextran sodium sulfate (DSS)-induced colitis, a mouse model of inflammatory bowel disease (IBD). METHODS: Acute or chronic colitis was induced by administration of dextran sodium sulfate (DSS) in four groups of age-matched C57BL/6 female mice: (1) CD200-transgenic mice (CD200tg); (2) wild-type (WT) mice; (3) CD200 receptor 1-deficient (CD200R1KO) mice; and (4) CD200-deficient (CD200KO) mice. The extent of colitis was determined using a histological scoring system. Colon tissues were collected for quantitative RT-PCR and Immunohistochemical staining. Supernatants from colonic explant cultures and mononuclear cells isolated from colonic tissue were used for ELISA. RESULTS: CD200KO and CD200R1KO mice showed greater sensitivity to acute colitis than WT mice, with accelerated loss of body weight, significantly higher histological scores, more severe infiltration of macrophages, neutrophils and CD3+ cells, and greater expression of macrophage-derived inflammatory cytokines, whose production was inhibited in vitro (in WT/CD200KO mouse cells) by CD200. In contrast, CD200tg mice showed less sensitivity to DSS compared with WT mice, with attenuation of all of the features seen in other groups. In a chronic colitis model, greater infiltration of Foxp3+ regulatory T (Treg) cells was seen in the colon of CD200tg mice compared to WT mice, and anti-CD25 mAb given to these mice attenuated protection. CONCLUSIONS: The CD200:CD200R axis plays an immunoregulatory role in control of DSS induced colitis in mice. PMID- 26841122 TI - Deconstructing race and gender differences in adolescent obesity: Oaxaca-blinder decomposition. AB - OBJECTIVE: To analyze sources of racial and gender disparities in adolescent obesity prevalence in the United States using Oaxaca-Blinder decomposition. METHODS: Data were obtained from the National Youth Physical Activity and Nutrition Study, a 2010 nationally representative study of 9th-12th grade students. Obesity status was determined from objective height and weight data; weight-related behaviors and school, home, and environmental data were collected via questionnaire. Oaxaca-Blinder decomposition was used to independently analyze racial and gender obesity prevalence differences (PD), i.e., comparing Black girls to White girls, and Black girls to Black boys. RESULTS: Overall, measured characteristics accounted for 46.8% of the racial PD but only 11.9% of the gender PD. Racial PD was associated with Black girls having less fruit/vegetable access at home, obtaining lunch at school more often, and playing fewer sports than White girls. Gender PD was associated with differential associations between physical activity (PA) measures-including total activities in the past year and days of moderate to vigorous physical activity (MVPA) in the past week-and obesity. CONCLUSIONS: School lunch and home food environmental variables accounted for racial disparities, but not gender disparities, in obesity prevalence. Gender differences in mechanisms between PA and obesity should be explored further. PMID- 26841124 TI - Treatment of Subjective Total Insomnia After Suicide Attempt With Olanzapine and Electroconvulsive Therapy. PMID- 26841125 TI - TOLERABILITY AND TUMOR RESPONSE OF A NOVEL LOW-DOSE PALLIATIVE RADIATION THERAPY PROTOCOL IN DOGS WITH TRANSITIONAL CELL CARCINOMA OF THE BLADDER AND URETHRA. AB - Previously reported radiation protocols for transitional cell carcinoma of the canine lower urinary tract have been ineffective or associated with increased side effects. Objectives of this retrospective, cross-sectional study were to describe safety of and tumor responses for a novel palliative radiation protocol for transitional cell carcinoma in dogs. Included dogs had cytologically or histologically confirmed transitional cell carcinoma of the bladder or urethra, and were treated with 10 once-daily fractions (Monday-Friday) of 2.7 Gy. Thirteen dogs were sampled, with six treated using radiation as first-line (induction) therapy and seven treated using radiation as rescue therapy after failing previous chemotherapy. Within 6 weeks of radiation, 7.6% (1/13) dogs had a complete response, 53.8% (7/13) partial response, 38.5% (5/13) stable disease, and none had progressive disease. Three patients presenting with urethral obstruction had spontaneous micturition restored during the treatment protocol. A single patient with unilateral ureteral obstruction was patent at recheck examination. Median survival time from time of initial diagnosis was 179 days. Median survival time from start of radiation was 150 days. Acute radiation side effects occurred in 31% (4/13) patients and were classified as grade 1 or 2. No significant late side radiation side effects were reported. No variables examined were identified as prognostic factors. Findings indicated that the reported radiation protocol was safe in this sample of dogs with bladder and urethral transitional cell carcinoma. Future prospective studies are needed to determine utility of this treatment as a rescue therapy in patients with complete urinary tract obstruction. PMID- 26841126 TI - Synthesis and Characterization of Paramagnetic Tungsten Imido Complexes Bearing alpha-Diimine Ligands. AB - Tungsten imido complexes bearing a redox-active ligand, such as N,N'-bis(2,6 diisopropylphenyl)-1,4-diaza-2,3-dimethyl-1,3-butadiene (L1), N,N'-bis(2,6 diisopropylphenyl)-1,4-diaza-1,3-butadiene (L2), and 1,2-bis[(2,6 diisopropylphenyl)imino]acenaphthene (L3), were prepared by salt-free reduction of W(?NC6H3-2,6-(i)Pr2)Cl4 (1) using 1-methyl-3,6-bis(trimethylsilyl)-1,4 cyclohexadiene (MBTCD) followed by addition of the corresponding redox-active ligands. In the initial stage, reaction of W(?NC6H3-2,6-(i)Pr2)Cl4 with MBTCD afforded a tetranuclear W(V) imido cluster, [W(?NC6H3-2,6-(i)Pr2)Cl3]4 (2), which served as a unique precursor for introducing redox-active ligands to the tungsten center to give the corresponding mononuclear complexes with a general formula of W(?NC6H3-2,6-(i)Pr2)Cl3(L) (3, L = L1; 4, L = L2; and 6, L = L3). X-ray analyses of complexes 3 and 6 revealed a neutral coordination mode of L1 and L3 to the tungsten in solid state, while the electron paramagnetic resonance (EPR) spectra of 3 and 4 clarified that a radical was predominantly located on the tungsten center supported by neutral L1 or L2, and the EPR spectra of complex 6 indicated that a radical was delocalized over both the tungsten center and the monoanionic redox-active ligand L3. PMID- 26841127 TI - A graphite calorimeter for absolute measurements of absorbed dose to water: application in medium-energy x-ray filtered beams. AB - The Italian National Institute of Ionizing Radiation Metrology (ENEA-INMRI) has designed and built a graphite calorimeter that, in a water phantom, has allowed the determination of the absorbed dose to water in medium-energy x-rays with generating voltages from 180 to 250 kV. The new standard is a miniaturized three bodies calorimeter, with a disc-shaped core of 21 mm diameter and 2 mm thickness weighing 1.134 g, sealed in a PMMA waterproof envelope with air-evacuated gaps. The measured absorbed dose to graphite is converted into absorbed dose to water by means of an energy-dependent conversion factor obtained from Monte Carlo simulations. Heat-transfer correction factors were determined by FEM calculations. At a source-to-detector distance of 100 cm, a depth in water of 2 g cm(-2), and at a dose rate of about 0.15 Gy min(-1), results of calorimetric measurements of absorbed dose to water, D(w), were compared to experimental determinations, D wK, obtained via an ionization chamber calibrated in terms of air kerma, according to established dosimetry protocols. The combined standard uncertainty of D(w) and D(wK) were estimated as 1.9% and 1.7%, respectively. The two absorbed dose to water determinations were in agreement within 1%, well below the stated measurement uncertainties. Advancements are in progress to extend the measurement capability of the new in-water-phantom graphite calorimeter to other filtered medium-energy x-ray qualities and to reduce the D(w) uncertainty to around 1%. The new calorimeter represents the first implementation of in-water phantom graphite calorimetry in the kilovoltage range and, allowing independent determinations of D(w), it will contribute to establish a robust system of absorbed dose to water primary standards for medium-energy x-ray beams. PMID- 26841128 TI - Extended Motor Evoked Potentials Monitoring Helps Prevent Delayed Paraplegia After Aortic Surgery. AB - OBJECTIVE: Motor evoked potentials (MEPs) monitoring can promptly detect spinal cord ischemia (SCI) from aortic clamping during open thoracoabdominal aneurysm repair (OTAAR) with distal aortic perfusion (DAP) and thus help decrease the risk of immediate postoperative SCI (IP-SCI). However, neither stable MEPs during aortic clamp interval (ACI) nor absence of IP-SCI eliminate the possibility of delayed postoperative SCI (DP-SCI). We hypothesized that extension of MEPs monitoring beyond ACI can also help decrease the risk of DP-SCI. METHODS: We identified 150 consecutive patients at our institution between April 2005 and October 2014 who underwent OTAAR with DAP and MEPs monitoring and had no IP-SCI. Using logistic regression analysis, we studied the independent effect of extended MEPs monitoring on the risk of developing DP-SCI. We used a propensity score analysis to adjust for potential confounders, such as poorly controlled hypertension, previous aneurysm surgery, splenectomy, acute aortic dissection, aneurysm type, older age, and history of diabetes and smoking. RESULTS: From the 150 patients, 129 (86%) remained neurologically intact whereas 21 (14%) developed DP-SCI. Nineteen of these twenty-one patients (90%) had no extended monitoring. Fifty-seven of fifty-nine (97%) patients who benefited from extended monitoring had no DP-SCI (p = 0.003). Extended MEPs monitoring was independently associated with decreased risk of DP-SCI (odds ratio = 0.14; 95% confidence interval: 0.03, 0.65; p = 0.01). INTERPRETATION: MEPs detect the lowest systemic blood pressure that ensures appropriate spinal cord perfusion in the postoperative period. Thus, they inform the hemodynamic management of patients post-OTAAR, particularly in the absence of a reliable neurological exam. PMID- 26841130 TI - Ligand-Stabilized Reduced-Dimensionality Perovskites. AB - Metal halide perovskites have rapidly advanced thin-film photovoltaic performance; as a result, the materials' observed instabilities urgently require a solution. Using density functional theory (DFT), we show that a low energy of formation, exacerbated in the presence of humidity, explains the propensity of perovskites to decompose back into their precursors. We find, also using DFT, that intercalation of phenylethylammonium between perovskite layers introduces quantitatively appreciable van der Waals interactions. These drive an increased formation energy and should therefore improve material stability. Here we report reduced-dimensionality (quasi-2D) perovskite films that exhibit improved stability while retaining the high performance of conventional three-dimensional perovskites. Continuous tuning of the dimensionality, as assessed using photophysical studies, is achieved by the choice of stoichiometry in materials synthesis. We achieve the first certified hysteresis-free solar power conversion in a planar perovskite solar cell, obtaining a 15.3% certified PCE, and observe greatly improved performance longevity. PMID- 26841129 TI - Pharmacoepidemiology of cytomegalovirus prophylaxis in a large retrospective cohort of kidney transplant recipients with Medicare Part D coverage. AB - We assembled a cohort of 21 117 kidney transplant patients from July 2006 to June 2011 with Medicare Part D coverage using US Renal Database System data to determine real-world use of cytomegalovirus (CMV) prophylaxis. CMV prophylaxis was defined as filled prescriptions for daily oral valganciclovir (<=900 mg), ganciclovir (<=3 g), or valacyclovir (6-8 g) within 28 d of transplant. Multilevel logistic regression analyses were performed to determine factors associated with CMV prophylaxis. CMV prophylaxis (97% valganciclovir) was identified in 61% of kidney transplant recipients (median duration, 64 d); 71% of seronegative recipients of kidneys from seropositive donors (D+/R-); 63% of R+ patients; 60% of patients with unknown serostatus; and 34% of D-/R- patients. Variability in usage of prophylaxis among transplant centers was greater than variability within transplant centers. One in four transplant centers prescribed CMV prophylaxis to >60% of their D-/R- patients. CMV donor/recipient serostatus, lymphocyte-depleting agents for induction and mycophenolate for maintenance were associated with CMV prophylaxis. CMV prophylaxis was commonly used among kidney transplant recipients. Routine prescription of CMV prophylaxis to D-/R- patients may have occurred in some transplant centers. Limiting unnecessary use of CMV prophylaxis may decrease healthcare costs and drug-related harms. PMID- 26841131 TI - Children Increase Their Sensitivity to a Speaker's Nonlinguistic Cues Following a Communicative Breakdown. AB - Bilingual children regularly face communicative challenges when speakers switch languages. To cope with such challenges, children may attempt to discern a speaker's communicative intent, thereby heightening their sensitivity to nonverbal communicative cues. Two studies examined whether such communication breakdowns increase sensitivity to nonverbal cues. English-speaking monolingual (n = 64) and bilingual (n = 54) 3- to 4-year-olds heard instructions in either English only or English mixed with a foreign language. Later, children played a hiding game that relied on nonverbal cues. Hearing a foreign language switch improved both monolingual and bilingual children's use of these cues. Moreover, bilinguals with more prior code-switching exposure outperformed those with less prior code-switching exposure. Children's short-term strategies to repair communication breakdowns may evolve into a more generalizable set of skills. PMID- 26841132 TI - Organocatalytic Enantioselective Synthesis of Tetrahydrofluoren-9-ones via Vinylogous Michael Addition/Henry Reaction Cascade of 1,3-Indandione-Derived Pronucleophiles. AB - An unprecedented organocatalytic enantioselective vinylogous Michael addition/Henry cyclization cascade is presented for the synthesis of highly substituted tetrahydrofluoren-9-ones 3 employing novel 1,3-indandione-derived pronucleophiles 1a-g and nitroalkenes 2. Following a very simple protocol, a wide range of products were obtained in good to excellent yields and with excellent enantioinduction (43-98% yield, up to 98% ee). The reaction proceeded with excellent diastereocontrol despite the simultaneous generation of four stereogenic centers. Surprisingly, when 2-(1-phenylethylidene)-1H-indandione (1h) was used as a pronucleophile, no cyclization was observed, and only Michael addition adducts 4a-x were furnished in very good yields and excellent enantioselectivities. PMID- 26841133 TI - Retrospective Single Center Study of Granulocyte Monocyte Adsorption Apheresis Treatment in Inflammatory Bowel Disease. AB - Patients with active inflammatory bowel disease (IBD) have elevated and activated myeloid leukocytes, which infiltrate the intestinal mucosa. A significant proportion of IBD patients do not respond adequately to conventional treatment regimes. Studies have suggested that treatment with granulocyte monocyte apheresis (GMA) could be a safe and efficacious alternative for these patients. We evaluated the efficacy and safety of granulocyte/monocyte apheresis in patients with IBD in a retrospective cohort study, conducted from a single center in Stockholm. Clinical details from consecutive apheresis treated patients were retrospectively reviewed from 2004 to 2012. A total of 37 patients were included, 23 patients with ulcerative colitis (UC) and 14 with Crohn's disease (CD). Clinical response was seen in 11 patients (30%) and complete remission in 11 patients (30%). The remission rate was higher in UC patients compared to CD patients, 39% (N = 9) and 14% (N = 2) respectively. A total of 9 patients experienced adverse events. Most frequently reported was headache (N = 4). GMA seems to be a valuable adjuvant treatment regime in the care of patients with refractory IBD. PMID- 26841134 TI - Extensive length variation in the ribosomal DNA intergenic spacer of yellow perch (Perca flavescens). AB - The intergenic spacer (IGS) is located between ribosomal RNA (rRNA) gene copies. Within the IGS, regulatory elements for rRNA gene transcription are found, as well as a varying number of other repetitive elements that are at the root of IGS length heterogeneity. This heterogeneity has been shown to have a functional significance through its effect on growth rate. Here, we present the structural organization of yellow perch (Perca flavescens) IGS based on its entire sequence, as well as the IGS length variation within a natural population. Yellow perch IGS structure has four discrete regions containing tandem repeat elements. For three of these regions, no specific length class was detected as allele size was seemingly normally distributed. However, for one repeat region, PCR amplification uncovered the presence of two distinctive IGS variants representing a length difference of 1116 bp. This repeat region was also devoid of any CpG sites despite a high GC content. Balanced selection may be holding the alleles in the population and would account for the high diversity of length variants observed for adjacent regions. Our study is an important precursor for further work aiming to assess the role of IGS length variation in influencing growth rate in fish. PMID- 26841135 TI - Cuby: An integrative framework for computational chemistry. AB - Cuby is a computational chemistry framework written in the Ruby programming language. It provides unified access to a wide range of computational methods by interfacing external software and it implements various protocols that operate on their results. Using structured input files, elementary calculations can be combined into complex workflows. For users, Cuby provides a unified and userfriendly way to automate their work, seamlessly integrating calculations carried out in different computational chemistry programs. For example, the QM/MM module allows combining methods across the interfaced programs and the builtin molecular dynamics engine makes it possible to run a simulation on the resulting potential. For programmers, it provides high-level, object-oriented environment that allows rapid development and testing of new methods and computational protocols. The Cuby framework is available for download at http://cuby4.molecular.cz. (c) 2016 Wiley Periodicals, Inc. PMID- 26841136 TI - Early Foetal Loss Correlates Positively with Seroconversion against Mycobacterium avium paratuberculosis in High-Producing Dairy Cows. AB - This study was designed to examine (i) the seroprevalence of Mycobacterium avium subs paratuberculosis (MAP) in a high-producing dairy herd with clinical symptoms of bovine paratuberculosis, (ii) MAP seroconversion and seronegativation dynamics in the herd and (iii) possible relationships between MAP infection status and herd reproductive performance. One single blood test per cow was performed early post-partum on a monthly basis from day 10-40 post-partum during the first year of the study in 519 cows belonging to a commercial dairy herd. A subset of 111 cows that became pregnant during the study was tested again 60-200 days later during the early foetal period, immediately after the first confirmation of gestation at 58-64 days post-AI. Logistic regression analysis indicated no effect of any independent variable on MAP seropositivity and conception rate 28-34 days post-AI. MAP seropositivity was not a factor affecting the anoestrous, subfertility and early foetal loss rates. In the subset of 111 cows, animals that seroconverted had a 3.9 times greater risk of suffering from early foetal loss (30.3%, 10/33) than the remaining pregnant animals (10.3%, 8/78), (95% confidence interval: 1.11-13.4; p = 0.003). In conclusion, early foetal loss was positively correlated with seroconversion to MAP. Reproductive performance was not impaired by MAP infection. PMID- 26841137 TI - Oil quality parameters and quantitative measurement of major secoiridoid derivatives in Neb Jmel olive oil from various Tunisian origins using qNMR. AB - BACKGROUND: Olive oil contains compounds with interesting biological activities which are influenced by the cultivar, the geographic origin and other factors. The aims of this work were to (1) investigate these factors in Neb Jmel olive oil from various Tunisian origins; (2) determine the influence of geographic conditions on phenolic composition of Neb Jmel olive oil and consequently on the antioxidant compounds; and (3) verify whether oils could be discriminated based on geographical origin. RESULTS: The characterisation of extra-virgin Neb Jmel olive oil produced in its original location has been conducted. Owing to the effect of the genotype and environmental, agronomic and technological factors on the chemical composition of olive oil and its quality, all studied olives were collected at the same season, and their oil obtained under the same processing technique. Many analyses were carried out to characterise the different olive oils: free acidity, peroxide value, fatty acid composition, Rancimat assay, pigments content and phenolic compounds by (1) H NMR. A recently developed method for the direct measurement of the oleocanthal and oleacein levels in olive oil by quantitative (1) H NMR was applied. The method was applied to the study of four Neb Jmel olive oils samples, and a broad variation of concentrations of all four secoiridoids was recorded. The concentration of each ranged from 55 to 529 mg kg( 1) and the sum of the four major secoiridoids (known as D3) ranged from 436 to 1063 mg kg(-1) . CONCLUSION: The quantification of major phenolic compounds of olive oil by NMR indicated that environmental conditions influence the production of qualitative phenolic fractions. All these compounds can be used as base 'markers' to characterise and differentiate these olive oil on geographic origin. (c) 2016 Society of Chemical Industry. PMID- 26841138 TI - Anion binding, electrochemistry and solvatochromism of beta-brominated oxoporphyrinogens. AB - Effects of macrocycle bromination on the structural, electrochemical and anion binding properties of 5,10,15,20-tetrakis(3,5-di-t-butyl-4-oxo-cyclohexa-2,5 dienylidene)porphyrinogen, OxP, are reported. Bromination of 5,10,15,20 tetrakis(3,5-di-t-butyl-4-hydroxyphenyl)-porphinatocopper(II), [T(DtBHP)P]Cu(II) yielded beta-Br8OxP, which was N-alkylated to beta-Br8OxPBz2 and beta-Br8OxPBz4 (where Bz = 4-bromobenzyl). beta-Br8OxPBz2 crystallizes in orthorhombic space group Pccn [a = 23.5535(17) A, b = 19.3587(14) A c = 20.9760(15) A, V = 9564.3(12) A3]. It has a calix[4]pyrrole-like structure with a saddle conformation and two molecules of methanol occupy a central binding site made up of the non-alkylated pyrrole N-H groups. Computational and electrochemical studies revealed widening HOMO-LUMO band gaps for the brominated compounds over the non-brominated analogues consistent with the observed hypsochromic shifts in electronic absorption spectra. Solvatochromic and chromogenic effects on anion binding were both observed for beta-Br8OxP and beta-Br8OxPBz2 with binding affinities of anions being greater than those observed for the corresponding OxP and OxPBz2. Colorimetric sensor studies suggest that the OxP compounds reported here are possible candidates for use in the design of optoelectronic noses for detection of anions and anionic analyte species of biological interest. PMID- 26841139 TI - Climatic Factors and Epidemiologic Characteristics of Head and Neck Skin Malignancies in Osijek Baranja County, Croatia. AB - AIM: The aim of this study was to investigate and compare the incidence and epidemiological characteristics of head and/or neck skin malignancies in Osijek Baranja County, Croatia, and to connect them with relative climatic indicators such as the number and intensity of sunny and cloudy days over a longer period of time. METHODS: The study included patients from Osijek Baranja County with confirmed pathohistological diagnosis of the head and/or neck malignancies from January 1, 2004 to December 31, 2012. The patients were analyzed according to gender, age, residence, occupation, type and location of the neoplasm, and hair and eye colour. The analysis of climatic elements (mean monthly and annual cloudiness values, mean monthly and annual sum values of sunny days) for a period of 50 years (1961-2011) based on the data of the Croatian Meteorological and Hydrological Service for the investigated area was performed. RESULTS: The study included a total of 2,952 patients: 1,487 (50.4%) males and 1,465 (49.6%) females, representing the estimated annual incidence of 104/100,000. The mean age was 72 years. The patients were mostly from rural areas, 1,952 (66.2%); 2,137 (72.4%) worked outdoors: 907 farmers (42.4%) and 889 construction workers (41.6%). Given the type of neoplasm, the most common was a basal cell cancer (BCC) in 2,160 patients (73.2%). Malignant melanoma was found in 93 patients (3.1%). The most common localizations were face (839 cases, 28.7%) and nose (643 cases, 22.0%). Males had a significantly higher number of planocellular malignancies--341 (56.6%) than females--262 (43.4%) (p=0.005). The median age of the patients was 67 years. There were no significant differences in types of malignancies, place of residence, workplace, or occupation (with respect to working outdoors or indoors). It has been shown that the ears and lips are significantly more affected by squamous cell malignancies (p=0.039 and p<0.001) compared to the neck, eye and head with malignant melanoma (p=0.004, p<0.001, and p=0.026) and the nose where basal cell neoplasms (p=0.002) prevail. There were no significant differences in the type and frequency of malignant neoplasms in relation to hair and eye colour of the patients. The last 50 years in Osijek Baranja County have seen a declining trend in the number of cloudy days and upward trend in the mean annual sum of sunny days. When compared, the increase in sunny days results in a higher number of patients suffering from malignant melanoma (rho=0.695, p=0.038). CONCLUSION: It is obvious that malignant neoplasms of the skin, head and neck occur after decades of exposure, and as a cumulative effect of exposure to risk factors. A direct exposure to sun seems to play an important role, especially with regard to melanoma. Nevertheless, further research is needed. PMID- 26841140 TI - Validity of Asthma Control Test in Assessing Asthma Control in Czech Outpatient Setting. AB - AIM: The aim of the study was to determine the reliability and validity of the agreement between the Asthma Control Test (ACT) and Global Initiative for Asthma (GINA) in classifying asthma control in the Czech Republic. METHODS: A sample of 316 people with asthma was recruited from the Clinic of Tuberculosis and Respiratory Diseases of the University Hospital in Ostrava between November 2011 and July 2012. Two questionnaires were used in this study, the Asthma Control Test and Mini Asthma Quality of Life Questionnaire (Mini-AQLQ). Regardless of the questionnaire results the asthma specialist assessed the asthma control status of enlisted patients according to the criteria described in the GINA 2006 guidelines. RESULTS: The internal consistency of the five-item ACT was good. The ACT score of >=20 predicted GINA-defined controlled asthma in 29% of cases with a sensitivity of 65% and specificity of 89%. The kappa level of agreement between the ACT classification and GINA classification of asthma control was 0.29, suggesting fair agreement. The ACT score showed the strongest correlation with the specialists' rating, followed by the FEV1 percent predicted. Overall, in line with previous studies we confirmed significant relationship between the ACT scores and FEV1 and health related quality of life. CONCLUSIONS: ACT is a reliable and simple tool that might be a significant asset in the management of outpatients with asthma in the Czech Republic. The ACT score correlates well with lung function parameters and health related quality of life. It appears to be a good tool to predict GINA-defined 'not-controlled asthma'. PMID- 26841141 TI - Asthma Exacerbations and Symptom Variability in Children Due to Short-term Ambient Air Pollution Changes in Ostrava, Czech Republic. AB - AIM: The Ostrava region suffers from high levels of air pollution during winter inversions. We investigated the association between short-term elevations of air pollutant concentrations and worsening of respiratory problems, use of asthma medication and restriction of daily activities in asthmatic patients in Ostrava. METHODS: One-hundred and forty-seven child and adolescent patients (aged 6-18 years) with a confirmed diagnosis of mild to moderate persistent asthma were included in the study. Participants' parents completed diaries covering the period of November 2013 to February 2014; this analysis included 18,228 person days. Daily smoothed maps of outdoor concentrations of particulate matter (PM10), nitrogen dioxide (NO2) and sulphur dioxide (SO2) were constructed from routine monitoring data, and participants' daily exposures were estimated on the basis of time spent at home and at school. The associations between health outcomes and exposure to air pollutants were estimated using the multiple logistic regression method. RESULTS: The odds ratios (OR) of the combined outcome for wheezing and/or difficulty in breathing, per 10 ug/m3 increase in the mean 24-h exposure were 1.07 (95% confidence interval 1.04-1.11) for PM10, 1.30 (1.18-1.44) for NO2, and 1.37 (1.18-1.59) for SO2. Additional inhaler use (in addition to usual medication) was also more frequent at higher air pollutant concentrations; the odds ratios per 10 ug/m3 increase in the mean 24-h exposure were 1.05 (1.02-1.07) for PM10, 1.19 (1.10-1.30) for NO2, and 1.26 (1.11-1.43) for SO2. Associations were less consistent for other health outcomes. CONCLUSIONS: These results suggest moderately strong associations between air pollutant concentrations and respiratory difficulties among asthmatic children and adolescents. More detailed analyses are required to confirm these preliminary findings. PMID- 26841142 TI - Socioeconomic Disparities in Age of Initiation and Ever Tobacco Smoking: Findings from Romania. AB - AIM: Smoking initiation is considered the fundamental behaviour that determines the future health burden of tobacco smoking in a society. The aim of the study was to evaluate the socio-demographic factors associated with initiation of regular smoking among adults. METHODS: The data source was the 2011 Global Adult Tobacco Survey Romania (GATS), which is a cross-sectional, nationally representative study. Multivariate logistic regression model was applied for relevant analysis. RESULTS: Among males, the regular smoking initiation rate was significantly higher compared to females (52.4% vs. 18.5%; p<0.001). Mean age of smoking initiation was lower in men compared to women (18.4+/-4.8 vs. 21.5+/-6.8; p<0.001). Age in men, awareness of environmental tobacco smoke consequences and place of living for women as well as educational attainment and employment status in both genders were associated with ever regular smoking. Moreover, cohabitation with a smoker was associated with greater odds for initiating smoking among both genders. CONCLUSIONS: GATS revealed a significant but diverse role of socioeconomic factors in initiation of regular smoking among adult Romanians. PMID- 26841144 TI - Housing Satisfaction in Finland with Regard to Area, Dwelling Type and Tenure Status. AB - AIM: This study presents a comprehensive examination of housing satisfaction in Finland and how it associates with different types of residential area, dwelling and tenure status taking into account socio-demographic and socioeconomic variables. METHODS: Associations between housing satisfaction and types of residential area, dwelling and tenure status were analysed by multivariate logistic regression using questionnaire data from a random sample of Finnish households (response rate 44%, N=1,308). RESULTS: Respondents from rural areas and those living in houses were statistically significantly (p<0.05) more satisfied with indoor thermal conditions in summer than respondents living in city centres (OR 2.01) and apartments (OR 1.75), respectively. Homeowners were more satisfied with the dwelling (OR 3.19), indoor air quality (OR 1.73) and thermal conditions in winter (OR 2.63), and reported moisture or mould damage (OR 0.37) and neighbour noise disturbance (OR 0.60) less frequently than tenants. CONCLUSION: Based on this study, the most important factors determining differences in housing satisfaction were tenure status and type of the dwelling. In the context of housing policy development, these results warrant a special consideration of housing quality in rental apartments. The results can also be used for making comparative assessments (e.g. detecting areas of relative strengths or needing improvement) of multifamily buildings and residential areas. PMID- 26841143 TI - Eating Habits and Dietary Intake: Is Adherence to Dietary Guidelines Associated with Importance of Healthy Eating among Undergraduate University Students in Finland? AB - AIM: Poor eating habits among young adults are a public health concern. This survey examined the eating habits of undergraduate university students in Finland. We assessed students' dietary intake of a variety of food groups, their adherence to international dietary guidelines (whole sample and by gender), and the associations between importance of eating healthy and dietary guidelines adherence (whole sample and by gender). METHODS: During the 2013-2014 academic year, 1,189 undergraduate students enrolled at the University of Turku in southwestern Finland completed an online self-administered questionnaire. Students reported their eating habits of 12 food groups, the number of daily servings of fruits/vegetables they consume and how important it is for them to eat healthy. For dietary adherence recommendations, we employed WHO guidelines. Chi-square statistic tested the differences in dietary guidelines adherence between males and females and also the associations between the gradients of importance of healthy eating and the self reported eating habits for each of the food groups, for the whole sample and by gender. RESULTS: We observed high levels of dietary adherence (>70%) for most of the 'unhealthy food' items (cake/cookies, snacks, fast food/canned food, and lemonade/soft drinks), and moderate adherence for most of the 'healthy food' items (>50%) (dairy/dairy products, fruit/vegetables servings/day, fresh fruit, salads/raw vegetables and cereal/cereal products). Fish/seafood, meat/sausage products and cooked vegetables had levels <50% for adherence to the guidelines. Women had better adherence for meat/sausage products, fast food/canned food and for most 'healthy food' items (p<=0.001), whereas men had better adherence for sweets (difference=12.8%, p<=0.001), lemonade/soft drinks (difference=16.7%, p<=0.001) and fish/seafood (difference=6.6%, p=0.040) compared to women. Most students considered important to eat healthy (78.8%). The importance of eating healthy was significantly associated with adherence for all food groups besides sweets and cake/cookies. These associations remained significant for women but some of them not for men (cereal/cereal products, snacks and sweets). CONCLUSIONS: The results suggest high adherence to the guidelines mainly for 'unhealthy food' groups, and moderate adherence for healthier food groups. There was also accordance between regarding eating healthy as important and actually eating healthy. However, there are improvements to be considered for specific food groups, as well as gender differences when implementing public health strategies related to food intake. PMID- 26841145 TI - Factors Associated with Parental Refusal of Routine Vaccination in the Czech Republic. AB - AIM: Routine vaccination is one of the most important preventive methods which is responsible for the decreasing trend of morbidity and mortality of vaccine preventable infectious diseases, their complications and sequelae. The impact of vaccination on declining trend of these diseases is well known and confirmed by a large number of epidemiological studies. In the Czech Republic, there is high vaccination coverage in regards to most vaccine preventable diseases. However, during the last decade proportion of parents refusing routine vaccination of their children due to different factors is increasing. The presented study evaluates current situation in the Czech Republic and describes the most significant factors in parents decision making. METHODS: The study was conducted between 1 July 2013 and 31 March 2014 as a questionnaire based survey (cross sectional study). The questionnaire was created with multiple choice answers. Questions were addressed to parents or legal representatives of children aged 0 18 years. Types of questions were divided into several subgroups. The study was performed in the Czech Republic in two different districts of Prague and Zlin. RESULTS: In the sample size (n=480) we detected 11 parents who refused vaccination of 11 children (2.29%). The most often refused vaccines in the prevalence study were hexavaccine (1st dose) and measles, mumps and rubella vaccine (1st dose). The hexavaccine includes tetanic anatoxin, diphtheric anatoxin, acellular pertussis vaccine, conjugate vaccine against Haemophilus influenzae b, inactivated polio vaccine, and recombinant vaccine against viral hepatitis B. The measles, mumps, rubella vaccine contains live attenuated viruses of measles, mumps, rubella. CONCLUSION: We observed increasing trend of routine vaccination refusal in children during the last ten years (compared to situation in the year 2004, p<0.001). The most important factors associated with this progression were distrust to vaccination, fear of some vaccine components and fear of adverse reactions. PMID- 26841146 TI - Assessing the Prevalence of Latent Tuberculosis among Health Care Providers in Zagazig City, Egypt Using Tuberculin Skin Test and QuantiFERON-TB Gold In-Tube Test. AB - AIM: Early detection of latent tuberculosis infection (LTBI) will prevent development of active TB among health care providers. The aim of the study was to assess the prevalence of LTBI among health care providers and compare the QuantiFERON-TB Gold In-Tube Test (QFT-GIT) and Tuberculin skin test in efforts to detect LTBI and to investigate possible associated risk factors of infection. METHODS: A cross sectional study was carried out during the period of 6 months in the Chest Hospital in Zagazig city and the Nephrology Unit at Zagazig University Hospitals in 132 randomly selected health care providers who were examined for LTBI by QFT-GIT and Tuberculin skin test and for the associated risk factors as well. RESULTS: The prevalence of LTBI identified by QFT-GIT and by Tuberculin skin test was 28.8% and 59.1%, respectively. Poor agreement was observed between the two tests (kappa=0.10). Working more than 10 years, being nurse, diabetic and smoker were risk factors significantly associated with LTBI (p<0.05). CONCLUSIONS: QFT-GIT is considered a useful tool in detecting LTBI cases, especially in a country where BCG vaccination is a national policy (as in Egypt). Duration of work, profession, diabetes and smoking are the risk factors for LTBI. Active surveillance and infection control measures are recommended to reduce the risk of LTBI. PMID- 26841147 TI - Monitoring of Microscopic Filamentous Fungi in Indoor Air of Transplant Unit. AB - AIM: The aim of the study was to control the microbial contamination of indoor air monitored monthly at the Transplant Unit of the University Hospital Olomouc from August 2010 to July 2011. METHODS: The unit is equipped with a three-stage air filtration system with HEPA filters. The MAS-100 air sampler (Merck, GER) was used. Twenty locations were singled out for the purposes of collecting a total of 720 samplings of the indoor air. Swabs of the HVAC diffusers at the sampling locations were always carried out after the sampling of the indoor air. RESULTS: In total, 480 samples of the indoor air were taken for Sabouraud chloramphenicol agar. In 11 cases (2.29%) the cultivation verified the presence of microscopic filamentous fungi. Only two cases involved the sanitary facilities of a patient isolation box; the other positive findings were from the facilities. The most frequent established genus was Aspergillus spp. (4x), followed by Trichoderma spp. (2x) and Penicillium spp. (2x), Paecilomyces spp., Eurotium spp., and Chrysonilia spp. (1x each). In 2 cases the cultivation established sterile aerial mycelium, unfortunately no further identification was possible. A total of 726 swabs of HVAC diffusers were collected (2 positive-0.28%). The study results demonstrated the efficacy of the HVAC equipment. CONCLUSIONS: With the continuing increase in the number of severely immunocompromised patients, hospitals are faced with the growing problem of invasive aspergillosis and other opportunistic infections. Preventive monitoring of microbial air contaminants is of major importance for the control of invasive aspergillosis. PMID- 26841148 TI - The Relationship between Levels of Physical Activity and Quality of Life among Students of the University of the Third Age. AB - AIM: The assessment of quality of life (QoL) among elderly people is of great importance when preparing health care programmes for this social group. Many researchers indicate that poor health is less frequently observed in senior citizens who display levels of physical activity (PA) prescribed by WHO. The aim of the study was to investigate the relationship between the level of PA among students of the University of the Third Age (U3A) and their self-assessment concerning their QoL. METHODS: The research sample consisted of 131 students from three U3A in West Pomeranian Voivodeship in Poland. PA was assessed with the aid of a short Polish version of the International Physical Activity Questionnaire (IPAQ). The assessment of QoL was conducted with the use of a Polish version of the WHO Quality of Life--BREF instrument (WHOQOL-BREF). RESULTS: The present study has shown that highly active U3A students declare high QoL in the psychological and social domains more often than other respondents. CONCLUSION: The level of PA recommended by WHO has a positive impact on the perceived QoL. Possible differences are visible mostly in the assessment of different domains of life in relation to the presented levels of PA. PMID- 26841149 TI - Percentile Values of Physical Fitness Levels among Polish Children Aged 7 to 19 Years--a Population-Based Study. AB - AIM: The objective of the study was to report gender and age-specific percentile values for fourteen commonly used field-based physical fitness tests among a national representative sample of Polish children aged 7 to 19 years. METHODS: A descriptive cross-sectional and population-based study examines the physical fitness among a random and large national representative sample of schoolchildren aged 7 to 19 years in Poland. A sample of 49,281 children and adolescents (25,687 boys and 23,594 girls) was assessed by the EUROFIT fitness test battery, the International Committee on the Standardization of Physical Fitness Tests and Cooper Test of physical fitness. The LMS statistical method was used. RESULTS: Smoothed gender and age-specific percentiles for the physical fitness tests in boys and girls aged 7 to 19 years are reported and expressed as both tabulated and curves values (2.3rd, 9th, 25th, 50th, 75th, 91st, and 97.7th). Figures showed greater physical fitness levels in boys, except for the flamingo balance, sit-and-reach, and stand-and-reach tests, in which girls performed slightly better. There was also a trend towards increased physical fitness levels as the age increased in both boys and girls. CONCLUSION: The percentile values provided will enable the correct interpretation and monitoring of fitness status of Polish children. PMID- 26841150 TI - Estimating the Baseline and Threshold for the Incidence of Diseases with Seasonal and Long-Term Trends. AB - In epidemiology, it is very important to estimate the baseline incidence of infectious diseases. From this baseline, the epidemic threshold can be derived as a clue to recognize an excess incidence, i.e. to detect an epidemic by mathematical methods. Nevertheless, a problem is posed by the fact that the incidence may vary during the year, as a rule, in a season dependent manner. To model the incidence of a disease, some authors use seasonal trend models. For instance, Serfling applies the sine function with a phase shift and amplitude. A similar model based on the analysis of variance with kernel smoothing and Serfling's higher order models, i.e. models composed of multiple sine-cosine function pairs with a variably long period, will be presented below. Serfling's model uses a long-term linear trend, but the linearity may not be always acceptable. Therefore, a more complex, long-term trend estimation will also be addressed, using different smoothing methods. In addition, the issue of the time unit (mostly a week) used in describing the incidence is discussed. PMID- 26841151 TI - Survey of Participation in Organised Cervical Cancer-Screening Programme in Hungary. AB - AIM: Cervical cancer mortality is high in Hungary, with more than 400 deaths per annum. In 2003, a national cervical cancer screening programme was launched to provide screening services for women who otherwise would not use services themselves. The aim of this survey was to study the socioeconomic and lifestyle factors related to participation in the organised cervical cancer screening programme. METHODS: A questionnaire-based health survey was conducted using a representative sample of women from 25-65 years of age in 11 Hungarian counties. A logistic regression analysis was used to study the association between participation in the screening programme and socioeconomic and lifestyle factors. RESULTS: 74% (95% CI: 70-77%) of the target population underwent a screening examination within the previous three years. Only 15% (95% CI: 5-35%) of the women, who received an invitation letter and took part in the organised screening programme, had never been previously examined by gynaecologist. The participation rates decreased significantly (p<0.05) for those subjects aged >44 years, retired, participants with low income, living in small settlements, and reported to be heavy smokers. CONCLUSION: Although the overall proportion of Hungary's population that undergoes regular screening for cervical cancer is not low, the organised national cancer screening programme was ineffective in engaging women not regularly visiting their gynaecologist for examination. PMID- 26841152 TI - Is Mild Cognitive Impairment a Precursor of Alzheimer's Disease? Short Review. AB - Mild Cognitive Impairment (MCI) may be a precursor of Alzheimer's disease (AD). There is a boundary area between normal aging and dementia. In practice, the term "age related cognitive decline" has been used interchangeably with "normal aging". Alternatively, the term "aging associated cognitive decline" was introduced and defined by a performance on a standardized cognitive scale focused on learning and memory, attention and cognitive speed, language, or visuoconstructional abilities. The term "mild cognitive impairment" was adopted by Petersen in 2004 to describe a period in the course of neurodegenerative disease where cognition is no longer normal relative to age expectations, however, daily functions are not sufficiently disrupted to correlate with the diagnosis of dementia. Most of the literature refers to the amnestic form of MCI, which is likely a precursor of AD. The rate of conversion from amnestic form of MCI to AD is estimated to reach 10-15% per year. That is why MCI generated a great deal of research. When considering MCI a precursor of AD, it seems reasonable to study AD genetic markers in the MCI patients. In AD, association studies focus on genetic polymorphisms assumed to have an effect on the expression and modulation function of genes associated with AD pathogenesis (ApoE, APP, presenilin 1, presenilin 2, tau protein), and on polymorphisms related to metabolism of the aforementioned proteins (splicing, degradation). Neuropsychological assesment plays a substantial role in the diagnosis of MCI, especially in the case of identification of different MCI subtypes or typical profiles of cognitive performance in prodromal phases of neurodegenerative diseases. The optimal composition of diet may increase an average age and prevent impairment of cognitive functions at the same time. Despite the progress in early diagnosis of MCI and dementia, further research is needed on differential diagnosis and treatment. In amnestic subtype of MCI some genetic markers may already be present, predicting possible future development of AD. Pointing to the need of secondary prevention, lifestyle modifications and possible early treatment could be implemented. PMID- 26841153 TI - Electrochemical fabrication and interfacial charge-transfer process of Ni/GaN(0001) electrodes. AB - The electrodeposition of Ni on single-crystal n-GaN(0001) film from acetate solution was investigated using scanning electron microscopy, X-ray diffraction, energy dispersive X-ray analysis, atomic force microscopy, and electrochemical techniques. The as-deposited Ni/n-GaN(0001) had a flat band potential of Ufb = 1.0 V vs. Ag/AgCl, which was much lower than that of bare GaN(0001). That is, a more feasible charge-transfer process occurred at the Ni/n-Ga(0001) interface. On the basis of a Tafel plot, an exchange current density of ~1.66 * 10(-4) mA cm( 2) was calculated. The nuclei density increased when the applied potential was varied from -0.9 V to -1.2 V and, eventually the whole substrate was covered. In addition, the current transient measurements revealed that the Ni deposition process followed instantaneous nucleation in 5 mM Ni(CH3COO)2 + 0.5 M H3BO3. PMID- 26841154 TI - Polycystic ovary syndrome: controversies and challenges. PMID- 26841156 TI - Cesarean delivery and prematurity. PMID- 26841157 TI - Is sulfadiazine alone equivalent (benefit and harm) to spiramycin to treat acute toxoplasmosis in the first trimester of pregnancy? PMID- 26841158 TI - Primary osteosarcoma of the breast: pathological and imaging findings. AB - Primary osteosarcoma of the breast (POB) is an extremely rare and aggressive tumor. Differential diagnosis of POB includes osteosarcoma of the chest wall and metaplastic breast carcinoma. Imaging tests that exclude the existence of a direct connection between the tumor and chest wall, as well as histopathological and immunohistochemical studies that rule out the presence of an epithelial component are required for the diagnosis of POB. We report a case of a 69-year old woman with POB. Imaging and pathological findings are presented. Therapeutic approach is discussed in the light of current knowledge, including potential complications. PMID- 26841159 TI - Nutritional practices and postnatal growth restriction in preterm newborns. AB - OBJECTIVE: to assess the nutritional practices in neonatal intensive care units (NICU) associated with growth retardation in premature (preterm) infants. METHODS: retrospective study of preterm infants weighing between 500 and 1,499 g admitted to NICU. Evolution of growth and parenteral (PN) and enteral (EN) nutrition practices were analyzed. RESULTS: among 184 preterm infants divided into G1 (500 to 990 g; n=63) and G2 (1000 to 1499 g; n=121), 169 received PN (G1=63, G2=106). Compared with the recommendations, PN was started late, its progress was slow and the maximum glucose, amino acid, lipid and energy supplies were low in both groups. The initial supply of amino acid and lipid and initial and maximum glucose and energy were lower in G1. The onset of EN was early (1-2 days), the time to reach exclusive EN was appropriate (11-15 days) and the use of human milk was possible in a reasonable amount of time (7-13 days). The multivariate analysis showed that respiratory distress syndrome and obtaining a supply of 120 kcal/kg/day too late increased the chance of weight loss greater than 10%. Sepsis, maximum energy supply for PN <60 kcal/kg/day and obtaining a supply of 120 kcal/kg/day too late increased the chance of regaining birth weight after 14 days, while small for gestational age (SGA) at birth reduced this chance. SGA at birth, sepsis and achieving exclusive enteral nutrition after 14 days increased the chance of being SGA at post-conceptual age of term. CONCLUSION: improving nutritional practices in the NICU can reduce the growth deficit in premature infants of very low birth weight. PMID- 26841160 TI - Evaluation of endometriosis-associated pain and influence of conventional treatment: a systematic review. AB - Endometriosis is a chronic gynecological disease characterized by sustained painful symptoms that are responsible for a decline in the quality of life of sufferers. Conventional treatment includes surgical and pharmacological therapy aiming at reducing painful symptoms. This study aimed to evaluate pain levels in women with endometriosis, focusing on the influence of conventional treatment in controlling this variable. To do so, a literature search was conducted in the Medline/Pubmed databases, with 119 scientific articles found. After applying the inclusion and exclusion criteria, 27 were selected for reading and elaboration of this review. Thus, 9 studies evaluated the contribution of surgery, 17 the use of drugs to reduce pain levels in patients with endometriosis and one assessed surgical and medical treatment. The main results of these searches are presented and discussed in this revision. Surgery and the use of drugs provided reduced pain scores in patients with endometriosis but nevertheless exhibit disadvantages, such as risk of recurrence and side effects, respectively. Treatment of endometriosis is, therefore, a challenge for gynecologists and patients, as they must select the best therapeutic approach for this disease. However, improved quality of life in these patients has been obtained with the use of conventional treatment. PMID- 26841161 TI - Nutritional aspects related to endometriosis. AB - This literature review analyzed the evidence on nutritional aspects related to the pathogenesis and progression of endometriosis. Diets deficient in nutrients result in changes in lipid metabolism, oxidative stress and promote epigenetic abnormalities, that may be involved in the genesis and progression of the disease. Foods rich in omega 3 with anti-inflammatory effects, supplementation with N-acetylcysteine, vitamin D and resveratrol, in addition to the increased consumption of fruits, vegetables (preferably organic) and whole grains exert a protective effect, reducing the risk of development and possible regression of disease. Dietary re-education seems to be a promising tool in the prevention and treatment of endometriosis. PMID- 26841162 TI - Elevated serum osteoprotegerin levels in women: friend or foe? AB - INTRODUCTION: osteoprotegerin has emerged as a new candidate for the treatment of osteoporosis. However, high levels of osteoprotegerin have been linked to vascular calcification, an independent and well-defined risk factor for cardiovascular disease (CVD) and mortality. Thus, the action of osteoprotegerin in these situations has been questioned. OBJECTIVE: to evaluate the effect of osteoprotegerin (OPG) on the human body, especially in bone tissue and in vascular diseases. METHODS: the scientific databases consulted were PubMed Medline and Cochrane, using keywords (MeSH terms) grouped into the following syntaxes: (Osteoprotegerin OR Osteoclastogenesis Inhibitory Factor OR Receptors, Tumor Necrosis Factor, Member 11b OR Tumor Necrosis Factor Receptor Superfamily, Member 11b OR FDCR-1 Protein OR FDCR 1 Protein OR OCIF Protein OR Follicular Dendritic Cell-Derived Receptor-1) AND (Bones AND Bone OR Bones AND Bone Tissue OR Bones OR Bone Tissue OR Cardiovascular Diseases). RESULTS: Osteoprotegerin is present in various organs and binds to two ligands: nuclear factor kB (RANKL) related to the differentiation of osteoclasts, and tumor necrosis factor related to the apoptosis-inducing ligand (TRAIL). OPG inhibits the regulation effects of nuclear factor kB on inflammation and on the skeletal and vascular systems, preventing the apoptosis induced by TRAIL, being related to the preservation of bone tissue. CONCLUSION: a deeper knowledge of the mechanisms involved in the association between OPG serum levels, bone integrity and cardiovascular disease can provide important data for future therapeutic interventions. PMID- 26841163 TI - Drilling: medical indications and surgical technique. AB - INTRODUCTION: anovulation is a major cause of female infertility, and polycystic ovary syndrome (PCOS) is the leading cause of anovulation. While undergoing drug induced ovulation, women with PCOS usually have a satisfactory response recruiting follicles, but some are unable to recruit follicles or often produce an excessive number of follicles, which can result in ovarian hyper-stimulation syndrome and/or multiple pregnancy. Surgical laparoscopy with ovarian "drilling" may prevent or reduce the need for drug-induced ovulation. OBJECTIVE: to identify the current indications of laparoscopic ovarian drilling and the best surgical technique. METHOD: a review of the medical literature based on systematic search in the Medline, Lilacs and Cochrane databases, using as keywords laparoscopy, polycystic ovary syndrome, and drilling. RESULTS: we found 105 articles in the literature, 27 of these highly relevant, describing findings on ovarian drilling. CONCLUSION: laparoscopic drilling is indicated for patients with polycystic ovary syndrome with ovulatory resistance to the use of clomiphene citrate, body mass index less than 30 kg/m2 and preoperative luteinizing hormone above 10 IU/L. The preferred surgical technique should be the realization of 5 to 10 perforations on the surface of each ovary bilaterally using monopolar energy. PMID- 26841164 TI - Cervical cancer: what's new? AB - Cervical cancer is the most common gynecological cancer in Brazil. Among women, it is the second most frequent, second only to breast cancer. It is the fourth leading cause of cancer death in the country, with estimated 15,590 new cases (2014) and 5,430 deaths (2013). In order to update information to improve outcomes, reduce morbidity and optimize the treatment of this cancer, this article will address the advancement of knowledge on cervical cancer. The topics covered include the role of surgery in different stages, treatment of locally advanced carcinomas, fertility preservation, the role of the sentinel lymph node technique, indications and techniques of radiotherapy and chemotherapy, and some special situations. PMID- 26841165 TI - Breast cancer: news in diagnosis and treatment. AB - The authors discuss the main innovations in the diagnosis and treatment of breast cancer, particularly in diagnostic imaging and screening, and in locoregional and systemic therapies. PMID- 26841166 TI - Female aging. AB - Female aging is a process that involves hypoestrogenism time, the individual impact on each woman, and what we can do as experts to reduce morbidity and provide quality of life. This natural process in the female life cycle has been of concern to women after menopause. Changes in different biophysical and psychosocial aspects, and their individual experiences, have repercussions on the lives of patients seeking specialized and multidisciplinary support to reduce the harmful effects of prolonged hypoestrogenism. Overweight and obesity, inadequate living habits and the presence of multi-morbidities cause damage to the quality of life and impact the functional capacity. Behavioral prescription and hormone therapy are among the treatments given to ease symptoms and reduce morbidity. A better understanding of these factors can help identify groups that require more care after menopause. PMID- 26841167 TI - Human reproduction: current status. AB - The concern about the maintenance of the human species has existed since the earliest civilizations. Progress in the diagnosis and treatment of infertility has led to the development of assisted reproductive techniques (ART) which, along with the evolution of genetics and molecular biology studies, have contributed in a concrete way to the management of infertile couples. Classic in vitro fertilization was initially developed 35 years ago for the treatment of women with tubal blockage, however, it remains inaccessible to a significant proportion of infertile couples around the world. This can be explained by the lack of specialized clinics in some countries and by the high cost of the procedures. Efforts have been employed to increase the number of treatment cycles for assisted reproduction, as for example, the creation of low-cost programs. Even today, infertility remains a problem of global proportions, affecting millions of couples. The estimate of the incidence of infertility is uncertain, mainly because of the criteria used for its definition. This article aims to review the most important aspects, succinctly, regarding the incidence, etiology, and treatment options available to infertile couples. PMID- 26841168 TI - Bioactive Constituents of Glycyrrhiza uralensis (Licorice): Discovery of the Effective Components of a Traditional Herbal Medicine. AB - Traditional herbal medicines have been reported to possess significant bioactivities. In this investigation, a combined strategy using both phytochemical and biological approaches was conducted to discern the effective components of licorice, a widely used herbal medicine. Altogether, 122 compounds (1-122), including six new structures (1-6), were isolated and identified from the roots and rhizomes of Glycyrrhiza uralensis (licorice). These compounds were then screened using 11 cell- and enzyme-based bioassay methods, including Nrf2 activation, NO inhibition, NF-kappaB inhibition, H1N1 virus inhibition, cytotoxicity for cancer cells (HepG2, SW480, A549, MCF7), PTP1B inhibition, tyrosinase inhibition, and AChE inhibition. A number of bioactive compounds, particularly isoprenylated phenolics, were found for the first time. Echinatin (7), a potent Nrf2 activator, was selected as an example for further biological work. It attenuated CCl4-induced liver damage in mice (5 or 10 mg/kg, ip) and thus is responsible, at least in part, for the hepatoprotective activity of licorice. PMID- 26841169 TI - Temporal Structure in Cooperative Interactions: What Does the Timing of Exploitation Tell Us about Its Cost? AB - Exploitation in cooperative interactions both within and between species is widespread. Although it is assumed to be costly to be exploited, mechanisms to control exploitation are surprisingly rare, making the persistence of cooperation a fundamental paradox in evolutionary biology and ecology. Focusing on between species cooperation (mutualism), we hypothesize that the temporal sequence in which exploitation occurs relative to cooperation affects its net costs and argue that this can help explain when and where control mechanisms are observed in nature. Our principal prediction is that when exploitation occurs late relative to cooperation, there should be little selection to limit its effects (analogous to "tolerated theft" in human cooperative groups). Although we focus on cases in which mutualists and exploiters are different individuals (of the same or different species), our inferences can readily be extended to cases in which individuals exhibit mixed cooperative-exploitative strategies. We demonstrate that temporal structure should be considered alongside spatial structure as an important process affecting the evolution of cooperation. We also provide testable predictions to guide future empirical research on interspecific as well as intraspecific cooperation. PMID- 26841171 TI - The Relative Importance of Post-Acute Care and Readmissions for Post-Discharge Spending. AB - OBJECTIVE: To understand what patterns of health care use are associated with higher post-hospitalization spending. DATA SOURCES: Medicare hospital, skilled nursing, inpatient rehabilitation, and home health agency claims, and Medicare enrollment data from 2007 and 2008. STUDY DESIGN: For 10 common inpatient conditions, we calculated variation across hospitals in price-standardized and case mix-adjusted Medicare spending in the 30 days following hospital discharge. We estimated the fraction of spending differences between low- and high-spending hospitals attributable to readmissions versus post-acute care, and within post acute care between inpatient rehabilitation facility (IRF) versus skilled nursing facility (SNF) use. For each service, we distinguished between differences in probability of use and spending conditional on use. DATA EXTRACTION METHODS: We identified index hospital claims and examined hospital and post-acute care occurring within a 30-day period following hospital discharge. For each Medicare Severity Diagnosis-Related Group (MS-DRG) at each hospital, we calculated average price-standardized Medicare payments for readmissions, SNFs, IRFs, and post-acute care overall (also including home health agencies and long-term care hospitals). PRINCIPAL FINDINGS: There was extensive variation across hospitals in Medicare spending in the 30 days following hospital discharge. For example, the interquartile range across hospitals ranged from $1,245 for chronic obstructive pulmonary disease to over $4,000 for myocardial infarction MS-DRGs. The proportion of differences attributable to readmissions versus post-acute care differed across conditions. For myocardial infarction, 74 to 93 percent of the variation was due to readmissions. For hip and femur procedures and joint replacement, 72 to 92 percent of the variation was due to differences in post acute care spending. There was also variation in the relative importance of the type of post-acute spending. For hip and femur procedures, joint replacement, and stroke, whether patients received IRF was the key driver of variation in post acute care spending In contrast, for pneumonia and heart failure, whether patients received SNF care was the key driver of variation in post-acute spending. CONCLUSIONS: Through initiatives such as bundled payment, hospitals are financially responsible for spending in the post-hospitalization period. The key driver of variation in post-hospitalization spending varied greatly across conditions. For some conditions, the key driver was having a readmission, for others it was whether patients receive any post-acute care, and for others the key driver was the type of post-acute care. These findings may help hospitals implement strategies to reduce post-discharge spending. PMID- 26841170 TI - Proposed Mode of Binding and Action of Positive Allosteric Modulators at Opioid Receptors. AB - Available crystal structures of opioid receptors provide a high-resolution picture of ligand binding at the primary ("orthosteric") site, that is, the site targeted by endogenous ligands. Recently, positive allosteric modulators of opioid receptors have also been discovered, but their modes of binding and action remain unknown. Here, we use a metadynamics-based strategy to efficiently sample the binding process of a recently discovered positive allosteric modulator of the delta-opioid receptor, BMS-986187, in the presence of the orthosteric agonist SNC 80, and with the receptor embedded in an explicit lipid-water environment. The dynamics of BMS-986187 were enhanced by biasing the potential acting on the ligand-receptor distance and ligand-receptor interaction contacts. Representative lowest-energy structures from the reconstructed free-energy landscape revealed two alternative ligand binding poses at an allosteric site delineated by transmembrane (TM) helices TM1, TM2, and TM7, with some participation of TM6. Mutations of amino acid residues at these proposed allosteric sites were found to either affect the binding of BMS-986187 or its ability to modulate the affinity and/or efficacy of SNC-80. Taken together, these combined experimental and computational studies provide the first atomic-level insight into the modulation of opioid receptor binding and signaling by allosteric modulators. PMID- 26841173 TI - [Innovation fund: An opportunity not to be missed]. PMID- 26841172 TI - Circadian Clock Regulates Bone Resorption in Mice. AB - The circadian clock controls many behavioral and physiological processes beyond daily rhythms. Circadian dysfunction increases the risk of cancer, obesity, and cardiovascular and metabolic diseases. Although clinical studies have shown that bone resorption is controlled by circadian rhythm, as indicated by diurnal variations in bone resorption, the molecular mechanism of circadian clock dependent bone resorption remains unknown. To clarify the role of circadian rhythm in bone resorption, aryl hydrocarbon receptor nuclear translocator-like (Bmal1), a prototype circadian gene, was knocked out specifically in osteoclasts. Osteoclast-specific Bmal1-knockout mice showed a high bone mass phenotype due to reduced osteoclast differentiation. A cell-based assay revealed that BMAL1 upregulated nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 (Nfatc1) transcription through its binding to an E-box element located on the Nfatc1 promoter in cooperation with circadian locomotor output cycles kaput (CLOCK), a heterodimer partner of BMAL1. Moreover, steroid receptor coactivator (SRC) family members were shown to interact with and upregulate BMAL1:CLOCK transcriptional activity. Collectively, these data suggest that bone resorption is controlled by osteoclastic BMAL1 through interactions with the SRC family and binding to the Nfatc1 promoter. (c) 2016 American Society for Bone and Mineral Research. PMID- 26841174 TI - [Hormone therapy through changing times]. AB - Despite several studies in the last years, only women with menopausal symptoms who desire therapy are treated. There is still no recommendation for menopausale hormone therapy for primary prevention of diseases such as coronary artery disease, osteoporosis or depression. The risk of thrombosis, pulmonary embolism and stroke is elevated especially for elderly women with oral hormone therapy. Benefits may exceed risks in younger, early-menopausal women, for whom hormone therapy may be prescribed more liberally. Systemic hormone therapy is for vasomotor symptoms, local therapy for the genitourinary syndrome of menopause. Choice of formulation depends on the individual risk due to symptoms and favours of the patients. With moderate to high cardiovascular risk profile, a transdermal route of estrogen application - in women with an intact uterus in combination with micronized progesterone - seems to be the best option. PMID- 26841175 TI - [Geriatric assessment in physicians' practices: evolution and current application]. AB - There is substantial variation in the health of the older population. Primary care physicians are in demand of a quick overview of their patients' health in order to determine who is at risk of decline and dependency. A geriatric assessment aims to meet these requirements. Its intention is to facilitate care tailored to the individual needs. The following article gives an account of how geriatric assessment is currently applied in primary care. It provides evidence as to its effectiveness and critically discusses the use of standard instruments. Currently, easy to administer instruments are being tested in primary care for targeting frail older people and assessing their needs. PMID- 26841176 TI - [New developments in Waldenstrom's macroglobulinemia]. AB - Waldenstrom's Macroglobulinemia (WM) is a rare subtype of B-cell lymphoma with mostly indolent course. Until now the backbone of therapy is still Rituximab / Chemotherapy. In recent years whole genome sequencing has revealed a number of genetic mutations, among them mutations of the MYD88 gene which occurs in over 90 % of patients and helps to validate diagnosis of WM in difficult cases. With the introduction of ibrutinib, an oral bruton-tyrosine-kinase inhibitor, an effective chemotherapy-free treatment option is available. PMID- 26841177 TI - [Asymptomatic bacteriuria]. AB - Asymptomatic bacteriuria is a diagnosis, which frequently leads to the unnecessary use of antibiotics. Recent studies demonstrate, that antibiotics have no advantage in this situation and that anibiotic stewardship interventions can effectively reduce the use of antimicrobial drugs. PMID- 26841178 TI - [Update cardiogenic shock]. AB - Although IABP support induces left ventricular unloading, these beneficial effect does not lead to improved microcirculation and survival. The use of percutaneous extracorporeal support systems (ECLS, ECMO) as well as left ventricular assist devices (pVAD) for adjunctive treatment of STEMI has increased during the recent years, but without sufficient evidence for a survival benefit. The PCI-access via the radial artery may lead to improved outcomes, especially in regard to survival. A liberal transfusion regimen for red cell packages in the perioperative phase of cardiac surgery seems to improve outcomes in regard to lower incidence of cardiogenic shock postoperatively. PMID- 26841179 TI - [Myocardial revascularisation in patients with reduced left ventricular function]. AB - Myocardial revascularization in patients with reduced left ventricular function remains a challenging clinical decision. The high mortality in these patients has been reduced by the routine use of guidelines-guided medical therapy for heart failure. However, myocardial revascularization additionally reduces cardiovascular mortality and improves functional outcome. Whether percutaneous coronary intervention or bypass surgery is indicated, should be decided individually with respect to comorbidities, morphology of the coronary vessels and the results of viability testing. PMID- 26841180 TI - [New aspects in prevention and therapy of diabetic nephropathy]. AB - The reduction of micro- and macrovascular end points in patients with diabetes mellitus type 2 is achieved by control of traditional risk factors such as hyperglycemia, hyperlipidemia, obesity and hypertension. However, most of the glucose lowering medication available is excreted by the kidney. Thus, in patients with diabetes-associated chronic kidney disease, the glucose lowering therapy has to account for renal function to avoid hypoglycemic episodes and other side effects such as lactic acidosis due to metformin. PMID- 26841181 TI - [Inhalation devices used in combination therapy in chronic airway disease]. AB - New fixed combinations of long acting beta2-agonists and anti-muscarinic agents have been launched in the therapy of chronic obstructive airway disease. The clinical benefit of the different drug combinations appears to be comparable. Differences however exist in the performance of the respective device. Proper training and repeated patient education is paramount for efficient therapy and appears to be more important than the choice of the drug itself. PMID- 26841182 TI - [Methotrexate - anchor drug in the treament of rheumatoid arthritis]. AB - Methotrexate is in the centre of the treatment of rheumatoid arthritis. There are new insights in the understanding of its mechanism: intracellular polyglutamation activates the methotrexate molecule. The magnitude of this step is associated with response to the treatment. Further on, it was found that even low doses of methotrexate are sufficient to guarantee its effect as comedication of TNF inhibitors. Finally, from the follow-up of long term cohorts it seems that methotrexate reduces mortality in rheumatoid arthritis independently from its effect on disease activity. PMID- 26841184 TI - [49-year-old woman with syncopes, dizziness and palpitations]. PMID- 26841183 TI - [Infections in inflammatory bowel disease]. AB - Infections significantly contribute to morbidity and mortality in inflammatory bowel diseases (IBD). Major risk factors for opportunistic infections in IBD include malnutrition, comorbidities, age and immunosuppression. While the risk of infection associated with corticosteroids, thiopurines, and TNFalpha antibodies has been determined in large, population-based studies, less is known about the risk associated with antibodies targeting gut-selective integrins. Furthermore, controversial data exist regarding the risk of infection under combined immunosuppression. In clinical practice, screening for infectious diseases before medical immunosuppression and delineation of disease flares from infectious complications remains of critical importance. PMID- 26841185 TI - [Work and training conditions of young German physicians in internal medicine. Results of a nationwide survey by young internists from the German Society of Internal Medicine and the German Professional Association of Internists]. AB - BACKGROUND: Major transformations within the German healthcare system (e. g. implementation of the G-DRG system, growing focus on economic aspects, demographic changes) led to changes of work and training conditions of young internists and to criticism and dissatisfaction. So far, there is a lack of up-to date and nationwide data analyzing these issues with focus on economic pressure and psychosocial strain. METHODS: The young internists of the two professional bodies conducted an online-based survey addressing all their members in training. The questionnaire covers five central areas of conflict. Furthermore, the model of effort-reward-imbalance (ERI) was applied to measure psychosocial strain at work. RESULTS: 1696 internists in training participated in the survey. Workdays characterized by high pace and workload do not leave much room for professional training as well as for family and research friendly working conditions. A relevant part of the affected physicians draws or at least considers personal consequences. Economical pressure is clearly noticeable. Psychosocial strain among the questioned internists is very high and conveys a risk for physicians' health and patients' quality of care. CONCLUSION: Adjustments of working and training conditions in internal medicine are necessary to preserve physicians health, high-quality medical treatment and to ensure an attractive working environment. PMID- 26841187 TI - [Thigh abscess as first manifestation of a sigma carcinoma]. AB - MEDICAL HISTORY: An extensive thigh abscess was the reason for a hospital admission of a 66 year old woman. Apart from that there were no other known preexisting diseases. INVESTIGATIONS: The reason for the abscess was a perforated sigma carcinoma, which was incidentally found. Treatments and course: We treated the patient with a sigma resection and several debridements of the thigh. But for all that she died from septic shock. CONCLUSION: This case illustrates the importance of cancer screening programs and an accurate investigation of the medical history and clinical examination. This can be supported by a failure management, which does not sanction a failure but considers it as a chance for future improvement. PMID- 26841186 TI - [Pseudoaneuryma after transradial puncture in systemic lysis of basilar artery thrombosis]. AB - HISTORY: Because of neurological symptoms as a result of thrombotic occlusion of the basilar artery, a successful revascularization after systemic Actilyse application was performed in a 78 year old patient. Later, it came to the formation of a pseudoaneurysm at the radial artery, punctured for invasive blood pressure measurement. TREATMENT AND COURSE: After oscillographic respectively ultrasound detection of a 2 cm wide pseudoaneurysm from the radial artery, the surgical resection of the aneurysm sac was performed. An ultrasound-guided manual compression due to the localization of a thrombus close to the aneurysm neck could not be conducted. The further clinical course was unremarkable. CONCLUSION: With an increasing number of pseudoaneurysms as a complication of transradial puncture occuring more frequently in the context of intensive care supply and rising outpatient cardiac catheterization (coronary angiography and PCI), the knowledge of care options of vascular complications are of particular importance before practical application. PMID- 26841189 TI - Limits of Molecular Dithienylethene Switches Caused by Ferrocenyl Substitution. AB - The efficiency of photochromic switches can be modified by attaching organic or organometallic groups to the photochromic core. We studied ferrocene-substituted dithienylethene switches differing by the size of the cycloalkene ring bridging the two thiophene groups. The results were compared with their chlorine substituted counterparts and an ethynyl-ferrocene substituted switch published earlier by Guirado and co-workers. From the measured UV/Vis spectra, both ferrocene-substituted compounds were found to be considerably less likely to switch than the corresponding chlorine-substituted ones. Kohn-Sham density functional theory calculations suggested that this is due to a multitude of energetically close-lying excited states in the former, which may offer multiple pathways for excitation and relaxation, out of which only one leads to ring opening or closing. By contrast, the chlorine-substituted switches have one energetically more isolated state that is responsible for the switching. The increase in the available excited states in the ferrocene-substituted switches was attributed to mixing between orbitals from the ferrocene units and the pi system of the bridge. PMID- 26841188 TI - What you need is what you eat? Prey selection by the bat Myotis daubentonii. AB - Optimal foraging theory predicts that predators are selective when faced with abundant prey, but become less picky when prey gets sparse. Insectivorous bats in temperate regions are faced with the challenge of building up fat reserves vital for hibernation during a period of decreasing arthropod abundances. According to optimal foraging theory, prehibernating bats should adopt a less selective feeding behavior--yet empirical studies have revealed many apparently generalized species to be composed of specialist individuals. Targeting the diet of the bat Myotis daubentonii, we used a combination of molecular techniques to test for seasonal changes in prey selectivity and individual-level variation in prey preferences. DNA metabarcoding was used to characterize both the prey contents of bat droppings and the insect community available as prey. To test for dietary differences among M. daubentonii individuals, we used ten microsatellite loci to assign droppings to individual bats. The comparison between consumed and available prey revealed a preference for certain prey items regardless of availability. Nonbiting midges (Chironomidae) remained the most highly consumed prey at all times, despite a significant increase in the availability of black flies (Simuliidae) towards the end of the season. The bats sampled showed no evidence of individual specialization in dietary preferences. Overall, our approach offers little support for optimal foraging theory. Thus, it shows how novel combinations of genetic markers can be used to test general theory, targeting patterns at both the level of prey communities and individual predators. PMID- 26841190 TI - Pre-conception public health to address maternal obesity. PMID- 26841192 TI - Giant cell hepatitis with autoimmune hemolytic anemia in a Korean infant. AB - Giant cell hepatitis (GCH) with autoimmune hemolytic anemia (AHA) is a very rare disease characterized by early onset and severe clinical manifestations, including immune hemolytic anemia and hepatitis with cholestasis. The prognosis is poor despite aggressive immunosuppressive therapy. We report here the first case of GCH with AHA in East Asia. A 2-month-old boy was admitted with jaundice. Blood test indicated abnormal liver function and low hemoglobin. Direct Coombs test and several autoantibodies associated with liver disease were positive, and liver biopsy was consistent with GCH. He was treated with prednisolone and ursodeoxycholic acid, and at the time of writing was in clinical and biochemical remission after prednisolone was stopped. PMID- 26841193 TI - Frequent Emergency Department Utilizers Among Children with Cancer. AB - BACKGROUND: Pediatric frequent emergency department (ED) utilizers contribute a significant proportion of ED visits, but no studies specifically address children with cancer. METHODS: A retrospective study of Pediatric Health Information System analyzing ED visits for children with cancer, including ED visits within 365 days from the first inpatient encounter with a discharge diagnosis code for malignancy. We defined frequent ED utilizers as those with four or more visits in the year (top 10th percentile). Patient characteristics and ED services (medications, laboratory, or imaging) for discharged children were assessed. Factors associated with being a frequent ED utilizer were examined with multivariable regression. RESULTS: Frequent utilizers accounted for 58% of ED visits. Frequent utilizers differed from infrequent utilizers in terms of type of cancer; 39.3% of frequent utilizers had acute lymphoblastic leukemia (ALL) and 16.0% had central nervous system (CNS) tumors compared with infrequent utilizers (21.9% had ALL and 24.8% CNS tumors, P-value < 0.001). Frequent utilization was associated with age 5-9 years (odds ratio [OR] = 1.4, 95% confidence interval [CI] 1.2-1.6) or 1-4 years (OR = 2.1, 95% CI 1.8-2.4) or <1 year (OR = 2.2, 95% CI 1.9-2.6) compared to 15-19 years and Hispanic ethnicity (OR 1.3, 95% CI 1.1 1.5) compared to white, non-Hispanics, and urban residence (OR = 1.5, 95% CI 1.3 1.7). Few children with cancer received no medication, laboratory, or imaging during their ED visit (frequent 11.0% vs. infrequent 12.5%, P = 0.01). CONCLUSIONS: The ED is integral to the care provided to children with cancer. The subset of frequent utilizers should be the focus of future research and quality improvement efforts. PMID- 26841191 TI - Proteome targets of ubiquitin-like samp1ylation are associated with sulfur metabolism and oxidative stress in Haloferax volcanii. AB - Small archeal modifier proteins (SAMPs) are related to ubiquitin in tertiary structure and in their isopeptide linkage to substrate proteins. SAMPs also function in sulfur mobilization to form biomolecules such as molybdopterin and thiolated tRNA. While SAMP1 is essential for anaerobic growth and covalently attached to lysine residues of its molybdopterin synthase partner MoaE (K240 and K247), the full diversity of proteins modified by samp1ylation is not known. Here, we expand the knowledge of proteins isopeptide linked to SAMP1. LC-MS/MS analysis of -Gly-Gly signatures derived from SAMP1 S85R conjugates cleaved with trypsin was used to detect sites of sampylation (23 lysine residues) that mapped to 11 target proteins. Many of the identified target proteins were associated with sulfur metabolism and oxidative stress including MoaE, SAMP-activating E1 enzyme (UbaA), methionine sulfoxide reductase homologs (MsrA and MsrB), and the Fe-S assembly protein SufB. Several proteins were found to have multiple sites of samp1ylation, and the isopeptide linkage at SAMP3 lysines (K18, K55, and K62) revealed hetero-SAMP chain topologies. Follow-up affinity purification of selected protein targets (UbaA and MoaE) confirmed the LC-MS/MS results. 3D homology modeling suggested sampy1ylation is autoregulatory in inhibiting the activity of its protein partners (UbaA and MoaE), while occurring on the surface of some protein targets, such as SufB and MsrA/B. Overall, we provide evidence that SAMP1 is a ubiquitin-like protein modifier that is relatively specific in tagging its protein partners as well as proteins associated with oxidative stress response. PMID- 26841194 TI - Adaptive flexibility of enzymatic antioxidants SOD, APX and CAT to high light stress: The clonal perennial monocot Iris pumila as a study case. AB - High solar radiation has been recognized as one of the main causes of the overproduction of reactive oxygen species (ROS) and oxidative stress in plants. To remove the excess of ROS, plants use different antioxidants and tune their activity and/or isoform number as required for given light conditions. In this study, the adaptiveness of light-induced variation in the activities and isoform patterns of key enzymatic antioxidants SOD, APX and CAT was tested in leaves of Iris pumila clonal plants from two natural populations inhabiting a sun exposed dune site and a forest understory, using a reciprocal-transplant experiment. At the exposed habitat, the mean enzymatic activity of total SODs was significantly greater than that in the shaded one, while the amount of the mitochondrial MnSOD was notably higher compared to the plastidic Cu/ZnSOD. However, the number of Cu/ZnSOD isoforms was greater in the forest understory relative to the exposed site (three vs. two, respectively). An inverse relationship recorded between the quantities of MnSOD and Cu/ZnSOD in alternative light habitats might indicate that the two enzymes compensate each other in maintaining intracellular ROS and redox balance. The adaptive population differentiation in APX activity was exclusively recorded in the open habitat, which indicated that the synergistic effect of high light and temperature stress could be the principal selective factor, rather than high light alone. The enzymatic activity of CAT was similar between the two populations, implicating APX as the primary H2O2 scavenger in the I. pumila leaves exposed to high light intensity. PMID- 26841195 TI - Determination of Right Ventricular Volume by Combining Echocardiographic Distance Measurements. AB - BACKGROUND: The position of the right ventricle (RV), often partly behind the sternum, implies difficulties to image the RV free wall using transthoracic echocardiography (TTE) and consequently limits the possibilities of stroke volume calculations. The aim of this study was to evaluate whether the volume of the right ventricle (RV) can be determined by combining TTE distance measurements that do not need the RV free wall to be fully visualized. METHODS: The RV volume was approximated by an ellipsoid composed of three distances. Distance measurements, modeled RV stroke volumes (RVSV), and RV ejection fraction (RVEF) were compared to reference values obtained from cardiac magnetic resonance (CMR) imaging for 12 healthy volunteers. RESULTS: Inter-modality comparisons showed that distance measurements were significantly underestimated in TTE compared to CMR. The modeled RV volumes using TTE distance measurements were underestimated compared to reference CMR volumes. There was, however, for TTE an agreement between modeled RVSV and left ventricular stroke volumes determined by biplane Simpson's rule. Similar agreement was shown between modeled RVSV based on CMR distance measurements and the CMR reference. Regarding RVEF, further studies including patients with a wider range of RVEF are needed to evaluate the method. CONCLUSION: In conclusion, the ellipsoid model of the RV provides good estimates of RVSVs, but volumes based on distance measurements from different modalities cannot be used interchangeably. PMID- 26841199 TI - Fluoroscopy-Guided Iliopsoas Injection: A Modified Approach. PMID- 26841197 TI - An examination of the role of autonomous versus controlled motivation in predicting inpatient treatment outcome for anorexia nervosa. AB - OBJECTIVE: We explored the effect of autonomous and controlled motivation on outcomes for patients undergoing inpatient treatment for Anorexia Nervosa (AN). METHOD: Data on 80 patients with AN were available for the start of treatment, and for 49 at end of treatment. Patients completed measures of autonomous and controlled motivation, eating disorder symptoms and attitudes, and comorbid psychopathology at the start and end of treatment. RESULTS: Patients showed significant improvements on eating symptoms and comorbid psychopathology over the course of treatment. Autonomous motivation was a significant predictor of change in severity of eating symptoms and attitudes such that patients with higher pre treatment levels of autonomous motivation showed larger post-treatment reductions on these indices. No such effects were associated with controlled motivation. DISCUSSION: This study highlights a relationship between autonomous motivation and outcome in an inpatient setting. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:626-629). PMID- 26841198 TI - Gender Differences in Patients with Fibromyalgia Undergoing Cognitive-Behavioral Therapy for Insomnia: Preliminary Data. AB - Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome that significantly affects patients' quality of life. Its main symptoms are pain, fatigue, and sleep disturbances. AIM: The aim of this study was to assess the efficacy of cognitive behavioral therapy for insomnia (CBT-I) in men and women with FM and compare sleep and clinical features between both genders. METHODS: Fifteen women and 13 men were selected to participate in nine weekly CBT-I sessions that involved completing several self-reported questionnaires at pretreatment, post-treatment, and follow-up. Patients were recruited from the Rheumatology Service and Pain Unit of Hospital and a fibromyalgia association. Group psychotherapy was performed at clinical unit of the Faculty of Psychology. RESULTS: Both groups showed significant clinical and statistical improvements in sleep quality and the main symptoms associated with FM (ie, pain intensity, fatigue, anxiety, pain catastrophizing, and pain-related anxiety). Differential treatment responsiveness between sexes was observed. Male group exhibited significant changes at post treatment in sleep disturbances and pain-related anxiety and catastrophizing. The female group showed post-treatment improvements in sleep latency, general fatigue, and depression, which persisted at follow-up. CONCLUSIONS: Differential responses to treatment between men and women were observed in some sleep- and pain-related variables. Outcomes show the needed to design different treatments for men and women with FM is discussed. PMID- 26841200 TI - Editorial Comment on Unexplained Profound Hypoglycemia After Vocal Fold Lipoinjection. PMID- 26841201 TI - Optimized Virtual Screening Workflow for the Identification of Novel G-Quadruplex Ligands. AB - G-quadruplexes, alternative DNA secondary structures present in telomeres, emerge as promising targets for the treatment of cancer, because they prevent telomere elongation and accordingly cell proliferation. Within this study, theoretically validated pharmacophore- and shape-based models as well as a theoretically validated docking protocol were generated and applied in parallel for virtual screening and the identification of novel G-quadruplex ligands. Top-ranked hits retrieved with all methods independently and in addition in a consensus approach were selected for biological testing. Of the 32 tested virtual hits seven selectively stabilized G-quadruplexes over duplex DNA in the fluorescence melting assay. For the five most active compounds, chemically closely related analogues were collected and subjected to in vitro analysis. Thereby, seven further novel G quadruplex ligands could be identified. These molecules do not only represent novel scaffolds, but some of them are in addition even more potent G-quadruplex stabilizers than the established reference compound berberine. This study proposes an optimized in silico workflow for the identification of novel G quadruplex stabilizers, which can also be applied in future studies. In addition, structurally novel and promising lead candidates with strong and selective G quadruplex stabilizing properties are reported. PMID- 26841202 TI - Albumin expression distinguishes bile duct adenomas from metastatic adenocarcinoma. AB - AIMS: Bile duct adenomas may be difficult to distinguish from metastatic carcinomas, particularly well-differentiated pancreatic ductal adenocarcinoma. Prior studies have evaluated the utility of various immunohistochemical markers, although these markers are notable for low sensitivity and/or specificity. The aim of this study was to investigate the utility of albumin and BRAFV600E expression in distinguishing between metastatic pancreatic adenocarcinoma and bile duct adenoma. METHODS AND RESULTS: We studied 26 bile duct adenomas, three bile duct hamartomas, and 158 pancreatic ductal adenocarcinomas. Branched-chain in-situ hybridization (bISH) for albumin was performed; bISH is based on the branched DNA technology, wherein signal amplification is achieved via a series of sequential steps. Additionally, BRAFV600E immunohistochemistry (IHC) was performed on a subset of cases. Twenty-three of 25 (92%) bile duct adenomas were positive for albumin; 18 (72%) showed diffuse staining, and five showed focal staining (20%), including two challenging examples. Two bile duct hamartomas also stained positively. All pancreatic adenocarcinomas were negative for albumin. Seven of 16 (44%) bile duct adenomas and five of 106 (5%) pancreatic ductal adenocarcinomas were positive for BRAFV600E by IHC. The sensitivity and specificity of expression of albumin, as detected by bISH, for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 92% and 100%, respectively; the sensitivity and specificity of BRAFV600E IHC for distinguishing bile duct adenomas from metastatic pancreatic adenocarcinomas were 43.8% and 95.3%, respectively. CONCLUSIONS: Diagnostically challenging examples of bile duct adenoma may be distinguished from metastatic pancreatic adenocarcinoma by the use of albumin bISH. PMID- 26841203 TI - Administration of G-CSF from day +6 post-allogeneic hematopoietic stem cell transplantation in children and adolescents accelerates neutrophil engraftment but does not appear to have an impact on cost savings. AB - G-CSF post-allogeneic HSCT accelerates neutrophil engraftment, but evidence that it impacts on cost-related outcomes is lacking. We performed a retrospective child and adolescent single-center cohort study examining G-CSF administration from Day +6 of allogeneic HSCT vs. ad hoc G-CSF use where clinically indicated. Forty consecutive children and adolescents undergoing allogeneic HSCT were included. End-points were as follows: time to engraftment; incidence of acute and chronic GvHD; number of patients alive at Day +100; 180-day TRM; post-transplant days in hospital; and cost of antimicrobials, TPN, and G-CSF usage. Neutrophil engraftment occurred earlier in the group that received G-CSF from Day +6. There was no difference between groups in any of the other end-points with the following exception: the cost of GCSF was significantly higher in the D + 6 G-CSF group. However, median G-CSF cost in this group amounted to only ?280. There was a trend towards reduced cost of antimicrobials in the D + 6 G-CSF group, although this did not reach significance (p = 0.13). The median cost per patient of antimicrobial agents between groups differed by ?1116. This study demonstrated the administration of G-CSF on Day +6 in pediatric HSCT to be safe. A further study using a larger cohort of patients is warranted to ascertain its true clinico-economic value. PMID- 26841205 TI - Trait anxiety but not state anxiety level associates with biomarkers for hypertension in the metabolic syndrome. AB - Various studies link hypertension with anxiety; however, it remains unclarified if such relations are present in the metabolic syndrome (MetS). We studied cross sectionally the interrelations of self-reported anxiety (Spielberger STAI), and MetS components in MetS patients. We investigated a nationally sampled treatment cohort for MetS with familial Type 2 diabetes risk. N = 101 patients fulfilling International Diabetes Federation criteria for MetS participated. Both laboratory and nonlaboratory measures were included. Structural equation models (SEM) were adjusted. The final SEM had an R(2) = .998 with the obesity component linking to waist, BMI, and degree of adiposity, and the hypertension component linking to systolic blood pressure, pulse pressure, total cholesterol, and trait anxiety. For state anxiety, no significant regressive causal path could be estimated. SEM supports the assumption of an interaction of pulse pressure, systolic blood pressure, cholesterol metabolism, and high trait anxiety in the pathophysiology of hypertension in MetS. PMID- 26841204 TI - Diblock Polyelectrolytic Copolymers Containing Cationic Iron and Cobalt Sandwich Complexes: Living ROMP Synthesis and Redox Properties. AB - Diblock metallopolymer polyelectrolytes containing the two redox-robust cationic sandwich units [CoCp'Cp](+) and [FeCp'(eta(6)-C6 Me6)](+) (Cp = eta(5)-C5 H5; Cp' = eta(5)-C5H4-) as hexafluorophosphate ([PF6](-)) salts are synthesized by ring opening metathesis polymerization using Grubbs' third generation catalyst. Their electrochemical properties show full chemical and electrochemical reversibilities allowing fine determination of the copolymer molecular weight using Bard-Anson's electrochemical method by cyclic voltammetry. PMID- 26841206 TI - L5/S1 Fusion Rates in Degenerative Spine Surgery: A Systematic Review Comparing ALIF, TLIF, and Axial Interbody Arthrodesis. AB - STUDY DESIGN: Systematic review. OBJECTIVE: To determine the fusion rate of an anterior lumbar interbody fusion (ALIF), transforaminal lumbar interbody fusion (TLIF), and axial arthrodesis at the lumbosacral junction in adult patients undergoing surgery for 1- and 2-level degenerative spine conditions. SUMMARY OF BACKGROUND DATA: An L5/S1 interbody fusion is a commonly performed procedure for pathology such as spondylolisthesis with stenosis; however, it is unclear if 1 technique leads to superior fusion rates. MATERIALS AND METHODS: A systematic search of MEDLINE was conducted for literature published between January 1, 1992 and August 17, 2014. All peer-reviewed articles related to the fusion rate of L5/S1 for an ALIF, TLIF, or axial interbody fusion were included. RESULTS: In total, 42 articles and 1507 patients were included in this systematic review. A difference in overall fusion rates was identified, with a rate of 99.2% (range, 96.4%-99.8%) for a TLIF, 97.2% (range, 91.0%-99.2%) for an ALIF, and 90.5% (range, 79.0%-97.0%) for an axial interbody fusion (P=0.005). In a paired analysis directly comparing fusion techniques, only the difference between a TLIF and an axial interbody fusion was significant. However, when only cases in which bilateral pedicle screws supported the interbody fusion, no statistical difference (P>0.05) between the 3 techniques was identified. CONCLUSIONS: The current literature available to guide the treatment of L5/S1 pathology is poor, but the available data suggest that a high fusion rate can be expected with the use of an ALIF, TLIF, or axial interbody fusion. Any technique-dependent benefit in fusion rate can be eliminated with common surgical modifications such as the use of bilateral pedicle screws. PMID- 26841207 TI - Are Jefferson Fractures With a Transverse Ligament Avulsion Potentially Unstable? PMID- 26841208 TI - Authorship Considerations: What Qualifies? AB - Publications indicate academic achievement. Unjustified authorship is a violation of scientific integrity. However, many different authorship guidelines have been purposed. Subjective assessments of contributions may differ substantially when made by individual authors. Complex research structures including multicenter multidisciplinary studies further cloud the definition of authorship. New quantitative measurement of research contributions may help guide who deserves to be recognized as an author. Agreement of authorship and order of listing should be discussed at the beginning of any project likely to result in a publication. PMID- 26841209 TI - Researchers' position statement on tackling obesity in pregnancy: the International Weight Management in Pregnancy (i-WIP) collaboration pleads for public health intervention. PMID- 26841210 TI - A single-institution study examining cutaneous and non-cutaneous melanomas treated with nivolumab. PMID- 26841211 TI - UNTREATED OBSTRUCTIVE SLEEP APNEA HINDERS RESPONSE TO BEVACIZUMAB IN AGE-RELATED MACULAR DEGENERATION. AB - PURPOSE: To compare functional and anatomical responses to intravitreal bevacizumab in patients with exudative age-related macular degeneration (AMD) between two groups of patients with obstructive sleep apnea (OSA) with and without treatment with continuous positive airway pressure therapy. METHODS: Patients with OSA were categorized into 2 groups: 18 untreated and 20 treated with continuous positive airway pressure therapy. All patients had exudative AMD and received treatment with intravitreal bevacizumab. Central retinal thickness was plotted against time to assess anatomical response. Logarithm of the minimum angle of resolution visual acuity changes determined functional effect. Total number of intravitreal injections administered was assessed. RESULTS: Treated OSA group received 8 +/- 7 total injections; untreated OSA group received 16 +/- 4 injections (P < 0.05). Treated OSA group achieved statistically significant better visual acuity (logarithm of the minimum angle of resolution, 0.3 +/- 0.24, 20/40), as opposed to the untreated group (logarithm of the minimum angle of resolution, 0.7 +/- 0.41; P < 0.05). Central retinal thickness improved in the treated OSA group compared with the untreated group: 358 +/- 95 MUm to 254 +/- 45 MUm and 350 +/- 75 MUm to 322 +/- 105 MUm, respectively (P < 0.05, 20/100). CONCLUSION: Untreated OSA hinders the response of exudative AMD to intravitreal bevacizumab. Treatment of OSA with continuous positive airway pressure therapy yields a subsequent anatomical response and functional improvement while requiring significantly less injections. Identifying and treating underlying OSA earlier in patients with exudative AMD may yield better functional outcomes. PMID- 26841212 TI - Correspondence. PMID- 26841213 TI - A Needle-Free Minimally Invasive Surgical Technique for the Placement of Silicone Oil Retention Sutures. PMID- 26841214 TI - How Was Your Sleep? New Implications for Obstructive Sleep Apnea in Retinal Disease. PMID- 26841215 TI - The Body Mass Index-Mortality Link across the Life Course: Two Selection Biases and Their Effects. AB - In this study, we investigated two selection biases that may affect the obesity mortality link over the life course: mortality selection and healthy participant effects. If these selection mechanisms are stronger among obese adults than among non-obese adults, they may contribute to the weakening obesity-mortality link over the life course. We used data from the National Health and Nutrition Examination Survey 1988-2010 with linked mortality files from 1988-2011. We employed weighted Cox models to test and adjust for these two selection biases. We also used complementary log-log models, adjusted for a normal distribution of frailty, to test for mortality selection effects; accelerated failure-time models to mitigate the mortality selection effect; and ordinary least squares regression to test for healthy participant effects. The link between class II/III obesity and mortality weakens at older ages. We did not find evidence for significant mortality selection or healthy participant effects. Also, even if the healthy participant effects were stronger among obese adults, they are not strong enough to produce a weakening association between obesity and morbidity at higher ages at the time of the survey. Therefore, neither of these selection biases explains the diminishing effect of class II/III obesity on mortality over the life course. PMID- 26841216 TI - Antenatal dietary and lifestyle advice for women who are overweight or obese and the effect on fetal growth and adiposity: the LIMIT randomised trial. AB - OBJECTIVE: To report the influence of maternal overweight and obesity on fetal growth and adiposity and effects of an antenatal dietary and lifestyle intervention among these women on measures of fetal growth and adiposity as secondary outcomes of the LIMIT Trial. DESIGN: Randomised controlled trial. SETTING: Public maternity hospitals in metropolitan Adelaide, South Australia. POPULATION: Pregnant women with a body mass index >= 25 kg/m(2), and singleton gestation between 10(+0) and 20(+0) weeks. METHODS: Women were randomised to Lifestyle Advice or continued Standard Care and offered two research ultrasound scans at 28 and 36 weeks of gestation. MAIN OUTCOME MEASURES: Ultrasound measures of fetal growth and adiposity. RESULTS: For each fetal body composition parameter, mean Z-scores were substantially higher when compared with population standards. Fetuses of women receiving Lifestyle Advice demonstrated significantly greater mean mid-thigh fat mass, when compared with fetuses of women receiving Standard Care (adjusted difference in means 0.17; 95% CI 0.02-0.32; P = 0.0245). While subscapular fat mass increased between 28 and 36 weeks of gestation in fetuses in both treatment groups, the rate of adipose tissue deposition slowed among fetuses of women receiving Lifestyle Advice, when compared with fetuses of women receiving Standard Care (P = 0.0160). No other significant differences were observed. CONCLUSIONS: These findings provide the first evidence of changes to fetal growth following an antenatal dietary and lifestyle intervention among women who are overweight or obese. PMID- 26841217 TI - The effect of antenatal lifestyle advice for women who are overweight or obese on secondary measures of neonatal body composition: the LIMIT randomised trial. AB - OBJECTIVE: To evaluate the effect of providing antenatal dietary and lifestyle advice on neonatal anthropometry, and to determine the inter-observer variability in obtaining anthropometric measurements. DESIGN: Randomised controlled trial. SETTING: Public maternity hospitals across metropolitan Adelaide, South Australia. POPULATION: Pregnant women with a singleton gestation between 10(+0) and 20(+0) weeks, and body mass index (BMI) >=25 kg/m(2). METHODS: Women were randomised to either Lifestyle Advice (comprehensive dietary and lifestyle intervention over the course of pregnancy including dietary, exercise and behavioural strategies, delivered by a research dietician and research assistants) or continued Standard Care. Analyses were conducted using intention to-treat principles. MAIN OUTCOME MEASURES: Secondary outcome measures for the trial included assessment of infant body composition using body circumference and skinfold thickness measurements (SFTM), percentage body fat, and bio-impedance analysis of fat-free mass. RESULTS: Anthropometric measurements were obtained from 970 neonates (488 Lifestyle Advice Group, and 482 Standard Care Group). In 394 of these neonates (215 Lifestyle Advice Group, and 179 Standard Care Group) bio-impedance analysis was also obtained. There were no statistically significant differences identified between those neonates born to women receiving Lifestyle Advice and those receiving Standard Care, in terms of body circumference measures, SFTM, percentage body fat, fat mass, or fat-free mass. The intra-class correlation coefficient for SFTM was moderate to excellent (0.55-0.88). CONCLUSIONS: Among neonates born to women who are overweight or obese, anthropometric measures of body composition were not modified by an antenatal dietary and lifestyle intervention. PMID- 26841218 TI - Retrospective Correlates for Bulimia Nervosa: A Matched Case-Control Study. AB - OBJECTIVE: There have been few studies investigating the risk factors for bulimia nervosa (BN), and most have been in Anglo-Saxon countries. This study aimed to (i) replicate the uncontested retrospective correlates for BN and clarify the role of factors with inconsistent findings and (ii) evaluate the strength of these factors in a different culture. METHOD: A case-control design was used to compare 60 women who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for BN to 60 healthy controls and 60 participants with other psychiatric disorders. Retrospective correlates were assessed by interviewing each person with the Oxford Risk Factor Interview. RESULTS: The primary retrospective correlates identified from the comparison of BN participants to healthy controls were general high maternal expectations, negative attitudes about parental weight and obesity in childhood and adolescence. Compared with participants with other psychiatric disorders, those with BN also reported higher rates of childhood obesity, deliberate self-harm, family conflicts, general high maternal expectations and feeling fat in childhood. CONCLUSIONS: The common findings across cultures suggest that, at least, individuals subjectively experience a number of similar factors that increase risk for developing BN. In addition, the difference regarding self-harm is notable. PMID- 26841220 TI - Fibrous-Root-Inspired Design and Lithium Storage Applications of a Co-Zn Binary Synergistic Nanoarray System. AB - Developing lithium ion batteries (LIBs) with fast charging/discharging capability and high capacity is a significant issue for future technical requirements. Transition-metal oxide (TMO) materials are widely studied as the next-generation LIB anode to satisfy this requirement due to their specific capacity, nearly three times than that of conventional graphite anode, and low cost. Meanwhile, they also suffer from slow lithium diffusion and limited electrochemical and structural stability, especially at high charging/discharging rate. The structure design of TMO is an effective strategy to obtain desirable LIB performance. Herein, inspired by natural fibrous roots consisting of functional and supporting units that can enhance substances and energy exchange efficiently, fibrous-root like Zn(x)Co(3-x)O4@Zn(1-y)Co(y)O binary TMO nanoarrays are designed and synthesized on Cu substrates through a facile one-pot, successive-deposition process for use as an integrated LIB anode. In a multilevel array ordered by orientation, ultrafine Zn(x)Co(3-x)O4 nanowire functional units and stable Zn(1 y)Co(y)O nanorod supporting units synergize, resulting in superior rate performance. At a high current density of 500 mAg(-1), they could maintain a discharge capacity as high as 804 mAh g(-1) after 100 cycles, working much higher than unary cobalt-based and zinc-based nanoarrays. This binary synergistic nanoarray system identifies an optimized electrode design strategy for advanced battery materials. PMID- 26841219 TI - Association of RAC1 Gene Polymorphisms with Primary End-Stage Renal Disease in Chinese Renal Recipients. AB - BACKGROUND/OBJECTIVE: RAC1 gene could influence susceptibility to renal failure by altering the activity and expression of Rac1, which is a member of the Rho family of small GTP-binding proteins. In clinical practice, renal transplantation provides the optimal treatment for people with end-stage renal disease (ESRD). The objective of this present study was to determine whether the RAC1 gene polymorphisms were associated with primary ESRD susceptibility in Chinese renal recipients. METHODS: Six single nucleotide polymorphisms (SNPs) of RAC1 gene, including rs836488 T>C, rs702482 A>T, rs10951982 G>A, rs702483 A>G, rs6954996 G>A, and rs9374 G>A, were genotyped in 300 renal transplant recipients (cases) and 998 healthy Chinese subjects (controls) by using TaqMan SNP genotyping assay. Allele, genotype, and haplotype frequencies of the six SNPs were compared between cases and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in logistic regression models to evaluate the associations of the six SNPs with ESRD risk. RESULTS: The genotype distributions for the six SNPs in controls were consistent with Hardy-Weinberg equilibrium (P > 0.05). Association analysis revealed that three SNPs were significantly associated with ESRD risk. Positive associations with ESRD risk were found for the rs836488, rs702482, and rs702483 in the co-dominant model (minor allele homozygotes versus major allele homozygotes); specifically, the frequencies of the minor allele homozygotes and the minor allele for the three SNPs were higher in the cases than in the controls. In addition, these three SNPs also had associations with increased ESRD risk under the additive model (P < 0.05), and positive associations were also found for the rs836488 in the dominant model (P < 0.05) and for the rs702483 in the recessive model (P < 0.05). All these associations were independent of confounding factors. The other three SNPs (rs10951982, rs6954996, and rs9374), in all comparison models, were not associated with ESRD risk (P > 0.05). In haplotype analysis, carriers with "C-T-G-G-G-G" haplotype had a significantly higher risk of ESRD compared with the most common haplotype "T-A-G-A-G-G" (P = 0.011, OR = 1.46, 95% CI = 1.09-1.94). CONCLUSION: This study suggested that polymorphisms of RAC1 gene might influence the susceptibility to ESRD in Chinese Han population. Further studies are necessary to confirm our findings. PMID- 26841222 TI - Transition of Inflammatory Bowel Disease Care: Assessment of Transition Readiness Factors and Disease Outcomes in a Young Adult Population. AB - BACKGROUND: Limited data exist on what factors impact transition readiness and how readiness impacts short-term disease outcomes. METHODS: Patients between the ages of 18 and 25 with an established inflammatory bowel disease diagnosis completed questionnaires at the time of an outpatient visit in the pediatric or adult setting, which included the Transition Readiness Assessment Questionnaire (TRAQ). After 6 months, electronic medical records were reviewed. RESULTS: A total of 95 patients were enrolled, 46 in the adult care setting and 49 in the pediatric care setting. Patients in the adult setting had a significantly higher overall TRAQ score compared with the pediatric setting (median: 4.42 [IQR: 3.9 4.6] versus 4.06 [IQR: 3.4-4.4], P < 0.001). Logistic regression analysis demonstrated that age was independently associated with higher TRAQ scores (odds ratio: 1.49; 95 confidence interval%, 1.1-2.02). Nonadherent patients scored lower on the Managing Medications subscale (median: 4.25 [IQR: 3.3-4.8] versus 4.75 [IQR: 4.3-5.0], P < 0.01). Logistic regression showed that patients who scored <4.75 on the Medication Management subscale were 3.8 times more likely to be nonadherent than patients who scored >=4.75 (95% confidence interval, 1.4 10.3). This remained significant after adjusting for gender and age. During the 6 month follow-up period, 9/95 patients (10%) had hospitalizations or ED visits related to inflammatory bowel disease. There were no associations between TRAQ scores and hospitalizations/ED visits. CONCLUSIONS: Age is the primary factor that drives transition readiness. Our findings suggest that administering the medication management portion of the TRAQ can be used to identify patients at risk for nonadherence. Follow-up studies are needed to determine how readiness impacts long-term disease outcomes. PMID- 26841221 TI - Role of GABAA-Mediated Inhibition and Functional Assortment of Synapses onto Individual Layer 4 Neurons in Regulating Plasticity Expression in Visual Cortex. AB - Layer 4 (L4) of primary visual cortex (V1) is the main recipient of thalamocortical fibers from the dorsal lateral geniculate nucleus (LGNd). Thus, it is considered the main entry point of visual information into the neocortex and the first anatomical opportunity for intracortical visual processing before information leaves L4 and reaches supra- and infragranular cortical layers. The strength of monosynaptic connections from individual L4 excitatory cells onto adjacent L4 cells (unitary connections) is highly malleable, demonstrating that the initial stage of intracortical synaptic transmission of thalamocortical information can be altered by previous activity. However, the inhibitory network within L4 of V1 may act as an internal gate for induction of excitatory synaptic plasticity, thus providing either high fidelity throughput to supragranular layers or transmittal of a modified signal subject to recent activity-dependent plasticity. To evaluate this possibility, we compared the induction of synaptic plasticity using classical extracellular stimulation protocols that recruit a combination of excitatory and inhibitory synapses with stimulation of a single excitatory neuron onto a L4 cell. In order to induce plasticity, we paired pre- and postsynaptic activity (with the onset of postsynaptic spiking leading the presynaptic activation by 10ms) using extracellular stimulation (ECS) in acute slices of primary visual cortex and comparing the outcomes with our previously published results in which an identical protocol was used to induce synaptic plasticity between individual pre- and postsynaptic L4 excitatory neurons. Our results indicate that pairing of ECS with spiking in a L4 neuron fails to induce plasticity in L4-L4 connections if synaptic inhibition is intact. However, application of a similar pairing protocol under GABAARs inhibition by bath application of 2MUM bicuculline does induce robust synaptic plasticity, long term potentiation (LTP) or long term depression (LTD), similar to our results with pairing of pre- and postsynaptic activation between individual excitatory L4 neurons in which inhibitory connections are not activated. These results are consistent with the well-established observation that inhibition limits the capacity for induction of plasticity at excitatory synapses and that pre- and postsynaptic activation at a fixed time interval can result in a variable range of plasticity outcomes. However, in the current study by virtue of having two sets of experimental data, we have provided a new insight into these processes. By randomly mixing the assorting of individual L4 neurons according to the frequency distribution of the experimentally determined plasticity outcome distribution based on the calculated convergence of multiple individual L4 neurons onto a single postsynaptic L4 neuron, we were able to compare then actual ECS plasticity outcomes to those predicted by randomly mixing individual pairs of neurons. Interestingly, the observed plasticity profiles with ECS cannot account for the random assortment of plasticity behaviors of synaptic connections between individual cell pairs. These results suggest that connections impinging onto a single postsynaptic cell may be grouped according to plasticity states. PMID- 26841223 TI - Colitis ImmunoPET: Defining Target Cell Populations and Optimizing Pharmacokinetics. AB - BACKGROUND: Positron emission tomography combined with a specific probe presents the ability to noninvasively assess inflammatory bowel disease. We previously reported increased intestinal uptake of a Cu-labeled anti-beta7 integrin antibody (clone FIB504.64) in colitic mice. Here, we evaluated an anti-alpha4beta7 integrin antibody (clone DATK32), and the F(ab')2 and Fab fragments of the anti beta7 antibody, which should have faster blood clearance than the intact antibody, as imaging probes for the detection of colitis in a mouse model. METHODS: The immunoproteins were labeled with Cu, injected into mice with dextran sodium sulphate-induced colitis. Positron emission tomography data were collected between 1 and 48 hours postinjection. RESULTS: Focal uptake of the anti-beta7 fragments was observed in the gut as early as 1 hour postinjection, and they cleared more rapidly from normal tissues than the whole antibody. For example, the blood concentrations at 24 hours postinjection were 23.3 +/- 3.0% ID/g for Cu labeled DATK32, 12.9 +/- 2.1% ID/g for FIB504.64, 4.1 +/- 0.4% ID/g for FIB504.64 F(ab')2, and 0.62 +/- 0.2% ID/g for FIB504.64-Fab (P < 0.0001, analysis of variance). The ratio of uptake of DATK32 between the colitis and control groups in the large intestine (1.38) was lower than for the FIB504.64 fragments (3.15 for F(ab')2, 1.84 for Fab) or intact FIB504.64 (1.78). CONCLUSIONS: The lower intestinal uptake ratio of the Cu-labeled anti-alpha4beta7 antibody (DATK32) compared with the anti-beta7 immunoproteins suggests that targeting all beta7 expressing lymphocytes, not just those expressing alpha4beta7, is a more promising route to the development of an inflammatory bowel disease imaging agent. The FIB504.64-F(ab')2 fragment demonstrated the greatest differential between colitis and control groups, and is therefore the most promising lead molecule for the development of an inflammatory bowel disease-specific imaging agent. PMID- 26841225 TI - Diet and Exacerbation of Inflammatory Bowel Disease Symptoms--Food for Thought. PMID- 26841224 TI - Controversies Revisited: A Systematic Review of the Comorbidity of Depression and Anxiety with Inflammatory Bowel Diseases. AB - BACKGROUND: Although mental health concerns are known to occur commonly for those with inflammatory bowel diseases (IBD), the nature of this comorbid relationship has not been systematically reviewed to date. A review in 2007 identified 5 controversies regarding anxiety/depression rates and various comparators between and within IBD. We aimed to systematically analyze and critique the current evidence regarding this comorbidity, providing an update to the 5 controversies. METHODS: Ebscohost Medline, CINAHL, Embase, and PsychINFO were searched between 2005 and 2014 using systematic review methodology. Controlled quantitative studies examining either symptoms or diagnoses of anxiety and depression in IBD were included in the review, with study quality assessed using a scale developed a priori to evaluate observational research. RESULTS: (1) IBD versus healthy controls (pooled mean proportions) (n = 13 studies): anxiety 19.1% versus 9.6%, depression 21.2% versus 13.4%; (2) IBD inactive versus IBD active disease (n = 26): anxiety 28.2% versus 66.4%, depression 19.9% versus 34.7%; (3) ulcerative colitis versus Crohn's disease (n = 28): anxiety 31% versus 37%, depression 22% versus 24.4%; (4) IBD versus other chronic medical conditions (n = 17): anxiety 41.9% versus 48.2%, depression 14.5% versus 28.4%; (5) onset of anxiety/depression before or after IBD onset (n = 2): adults more likely to develop anxiety/depression before IBD onset, but a substantial proportion develops depression after onset; an increased risk for children of developing anxiety/depression after IBD onset. CONCLUSIONS: The high rates of anxiety and depression for those with IBD, particularly when disease is active, warrant a systemic approach to screening and treatment. PMID- 26841226 TI - Cytologic and Histologic Features of Pleomorphic Undifferentiated Sarcoma Arising in a Hybrid Hemosiderotic Fibrolipomatous Tumor and Pleomorphic Hyalinizing Angiectatic Tumor: Report of an Unusual Case with a Literature Review. AB - BACKGROUND: Pleomorphic hyalinizing angiectatic tumor (PHAT) and hemosiderotic fibrolipomatous tumor (HFLT) are low-grade neoplasms that share clinicopathologic features and recurring translocation t(1;10)(p22;q24) involving the TGFBR3 and MGEA5 genes. Coexistence of these tumors with a high-grade sarcoma is exceedingly rare and the cytologic features have not been widely described in the literature. CASE: A 55-year-old female presented with a soft tissue tumor on the dorsum of the foot. Cytologic smears and corresponding core biopsies were composed of a population of markedly pleomorphic spindle cells seen singly and in loose clusters within a myxofibrous matrix and infiltrating fat, with coarse chromatin, prominent nucleoli, irregular nuclear contours and delicate to vacuolated cytoplasm. Intracytoplasmic hemosiderin granules and rare intranuclear cytoplasmic pseudoinclusions were identified. The histologic features of the excisional biopsy mirrored those of the cytologic preparations, but also demonstrated cellular foci of higher-grade sarcoma composed of markedly pleomorphic tumor cells with large vesicular nuclei and prominent nucleoli, exhibiting a mitotic index of 12 mitotic figures per 10 high-powered fields. CONCLUSION: While HFLT/PHAT generally can be managed by wide local excision, it is important to be aware of their capacity to harbor higher-grade lesions with metastatic potential which may require more radical surgical excision. PMID- 26841227 TI - Impact of solids retention time on dissolved organic nitrogen and its biodegradability in treated wastewater. AB - Dissolved organic nitrogen (DON) and its biodegradability in treated wastewater have recently gained attention due to increased regulatory requirements on effluent quality to protect receiving waters. Laboratory scale chemostat experiments were conducted at 9 different solids retention times (SRTs) (0.3, 0.7, 2, 3, 4, 5, 7, 8, and 13 days) to examine whether SRT could be used to control DON, biodegradable DON (BDON), and DON biodegradability (BDON/DON) levels in treated wastewater. Results indicated no trend between effluent DON and SRTs. Effluent BDON was comparable for SRTs of 0.3-4 days and had a decreasing trend with SRT after that. Effluent DON biodegradability (effluent BDON/effluent DON) ranging from 23% to 59% tended to decrease with SRT. Chemostat during longer SRTs, however, was contributing to non-biodegradable DON (NBDON) and this fraction of DON increased with SRT above 4 days. Model calibration results indicated that ammonification rate, and growth rates for ordinary heterotrophs, ammonia oxidizing bacteria and nitrite oxidizing bacteria were not constants but have a decreasing trend with increasing SRT. This study indicates the benefit of high SRTs in term of producing effluent with less DON biodegradability leading to relatively less oxygen consumption and nutrient support in receiving waters. PMID- 26841228 TI - Predicting concrete corrosion of sewers using artificial neural network. AB - Corrosion is often a major failure mechanism for concrete sewers and under such circumstances the sewer service life is largely determined by the progression of microbially induced concrete corrosion. The modelling of sewer processes has become possible due to the improved understanding of in-sewer transformation. Recent systematic studies about the correlation between the corrosion processes and sewer environment factors should be utilized to improve the prediction capability of service life by sewer models. This paper presents an artificial neural network (ANN)-based approach for modelling the concrete corrosion processes in sewers. The approach included predicting the time for the corrosion to initiate and then predicting the corrosion rate after the initiation period. The ANN model was trained and validated with long-term (4.5 years) corrosion data obtained in laboratory corrosion chambers, and further verified with field measurements in real sewers across Australia. The trained model estimated the corrosion initiation time and corrosion rates very close to those measured in Australian sewers. The ANN model performed better than a multiple regression model also developed on the same dataset. Additionally, the ANN model can serve as a prediction framework for sewer service life, which can be progressively improved and expanded by including corrosion rates measured in different sewer conditions. Furthermore, the proposed methodology holds promise to facilitate the construction of analytical models associated with corrosion processes of concrete sewers. PMID- 26841229 TI - Nutrient removal from horticultural wastewater by benthic filamentous algae Klebsormidium sp., Stigeoclonium spp. and their communities: From laboratory flask to outdoor Algal Turf Scrubber (ATS). AB - Benthic filamentous algae have evident advantages in wastewater treatment over unicellular microalgae, including the ease in harvesting and resistance to predation. To assess the potentials of benthic filamentous algae in treating horticultural wastewater under natural conditions in Belgium, three strains and their mixture with naturally wastewater-borne microalgae were cultivated in 250 ml Erlenmeyer flasks in laboratory as well as in 1 m(2) scale outdoor Algal Turf Scrubber (ATS) with different flow rates. Stigeoclonium competed well with the natural wastewater-borne microalgae and contributed to most of the biomass production both in Erlenmeyer flasks and outdoor ATS at flow rates of 2-6 L min( 1) (water velocity 3-9 cm s(-1)), while Klebsormidium was not suitable for growing in horticultural wastewater under the tested conditions. Flow rate had great effects on biomass production and nitrogen removal, while phosphorus removal was less influenced by flow rate due to other mechanisms than assimilation by algae. PMID- 26841230 TI - Natural solar photolysis of total organic chlorine, bromine and iodine in water. AB - Municipal wastewater has been increasingly used to augment drinking water supplies due to the growing water scarcity. Wastewater-derived disinfection byproducts (DBPs) may negatively affect the aquatic ecosystems and human health of downstream communities during water reuse. The objective of this research was to determine the degradation kinetics of total organic chlorine (TOCl), bromine (TOBr) and iodine (TOI) in water by natural sunlight irradiation. Outdoor solar photolysis experiments were performed to investigate photolytic degradation of the total organic halogen (TOX) formed by fulvic acid and real water and wastewater samples. The results showed that TOX degradation by sunlight irradiation followed the first-order kinetics with half-lives in the range of 2.6 10.7 h for different TOX compounds produced by fulvic acid. The TOX degradation rates were generally in the order of TOI > TOBr ? TOCl(NH2Cl) > TOCl(Cl2). High molecular weight TOX was more susceptible to solar photolysis than corresponding low molecular weight halogenated compounds. The nitrate and sulfite induced indirect TOX photolysis rates were less than 50% of the direct photolysis rates under the conditions of this study. Fulvic acid and turbidity in water reduced TOX photodegradation. These results contribute to a better understanding of the fate of chlorinated, brominated and iodinated DBPs in surface waters. PMID- 26841231 TI - Degradation of refractory pollutants under solar light irradiation by a robust and self-protected ZnO/CdS/TiO2 hybrid photocatalyst. AB - Photocatalyst plays a vital role in the photochemical water treatment. To improve the visible-light photoactivity of TiO2 for refractory pollutant degradation, CdS/TiO2 hybrids with different nanostructures have been prepared, but usually suffer from a low photocatalytic degradation efficiency and a rapid photocorrosion. In this work, we developed a synergistic ZnO/CdS/TiO2 hybrid, which could act as a robust and self-protected photocatalyst for water purification without additional sacrificial reagents. This was attributed to the two different junction mechanisms in one single hybrid. Photons were selectively adsorbed by ZnO and CdS, then, the electrons with a low reductive activity in ZnO recombined directly with the holes with a low oxidative activity in CdS, whereas the holes with a high oxidative activity in ZnO and the electrons with a high reductive activity in CdS were captured for catalytic reaction. The superiority of the novel ZnO/CdS/TiO2 hybrid over the traditional CdS/TiO2 hybrid in both photocatalytic activity and anti-photocorrosion capacity was demonstrated in the degradation of Atrazine and Rhodamine B, two typical refractory organic pollutants, and the treatment of real textile wastewater under solar light irradiation. The developed ZnO/CdS/TiO2 hybrid exhibited an excellent potential for the degradation of refractory pollutants, and provided a new way to advance intrinsically solar-susceptible catalyst for photochemical wastewater treatment. PMID- 26841232 TI - Occurrence and partition ratios of radiocesium in an urban river during dry and wet weather after the 2011 nuclear accident in Fukushima. AB - After the 2011 nuclear accident in Fukushima, radiocesium was released from the Fukushima Dai-ichi Nuclear Power Plant and contaminated waters in urban areas near Tokyo. By intensive field monitoring during 3 years, this study investigated the temporal trends and the occurrence of radiocesium during dry and wet weather, and analyzed the variations in radiocesium during rainfall events and factors controlling them. Concentrations of particulate radiocesium decreased rapidly from May 2012 to March 2013 and reached an equilibrium in 2014. Concentrations of particulate (137)Cs during wet weather were almost double those during dry weather in the same period. In contrast to the small variations in (137)Cs concentrations in the particulate phase on a suspended solids (SS) weight basis during events, those in the dissolved phase on a liquid-volume basis fluctuated greatly, resulting in variations in the partition coefficient (apparent Kd). The apparent Kd of (137)Cs during wet weather ranged from 30,000 to 150,000 L kg(-1) and showed a significant negative correlation with SS concentrations during wet weather. Specific surface area in solids contributed to the variations in apparent Kd. PMID- 26841233 TI - Empowering a mesophilic inoculum for thermophilic nitrification: Growth mode and temperature pattern as critical proliferation factors for archaeal ammonia oxidizers. AB - Cost-efficient biological treatment of warm nitrogenous wastewaters requires the development of thermophilic nitrogen removal processes. Only one thermophilic nitrifying bioreactor was described so far, achieving 200 mg N L(-1) d(-1) after more than 300 days of enrichment from compost samples. From the practical point of view in which existing plants would be upgraded, however, a more time efficient development strategy based on mesophilic nitrifying sludge is preferred. This study evaluated the adaptive capacities of mesophilic nitrifying sludge for two linear temperature increase patterns (non-oscillating vs. oscillating), two different slopes (0.25 vs. 0.08 degrees C d(-1)) and two different reactor types (floc vs. biofilm growth). The oscillating temperature pattern (0.25 degrees C d(-1)) and the moving bed biofilm reactor (0.08 degrees C d(-1)) could not reach nitrification at temperatures higher than 46 degrees C. However, nitrification rates up to 800 mg N L(-1) d(-1) and 150 mg N g(-1) volatile suspended solids d(-1) were achieved at a temperature as high as 49 degrees C by imposing the slowest linear temperature increase to floccular sludge. Microbial community analysis revealed that this successful transition was related with a shift in ammonium oxidizing archaea dominating ammonia oxidizing bacteria, while for nitrite oxidation Nitrospira spp. was constantly more abundant than Nitrobacter spp.. This observation was accompanied with an increase in observed sludge yield and a shift in maximal optimum temperature, determined with ex-situ temperature sensitivity measurements, predicting an upcoming reactor failure at higher temperature. Overall, this study achieved nitrification at 49 degrees C within 150 days by gradual adaptation of mesophilic sludge, and showed that ex-situ temperature sensitivity screening can be used to monitor and steer the transition process. PMID- 26841234 TI - Ideals versus reality: Are weight ideals associated with weight change in the population? AB - OBJECTIVE: To quantify weight ideals of young adults and to examine whether the discrepancy between actual and ideal weight is associated with 10-year body mass index (BMI) change in the population. METHODS: This study comprised 4,964 adults from the prospective population-based FinnTwin16 study. They reported their actual and ideal body weight at age 24 (range 22-27) and 10 years later (attrition 24.6%). The correlates of discrepancy between actual and ideal body weight and the impact on subsequent BMI change were examined. RESULTS: The discrepancy between actual and ideal weight at 24 years was on average 3.9 kg (1.4 kg/m(2) ) among women and 1.2 kg (0.4 kg/m(2) ) among men. On average, participants gained weight during follow-up irrespective of baseline ideal weight: women -x = +4.8 kg (1.7 kg/m(2) , 95% CI 1.6-1.9 kg/m(2) ), men -x = +6.3 kg (2.0 kg/m(2) , 95% CI 1.8-2.1 kg/m(2) ). Weight ideals at 24 years were not correlated with 10-year weight change. At 34 years, just 13.2% of women and 18.9% of men were at or below the weight they had specified as their ideal weight at 24 years. Women and men adjusted their ideal weight upward over time. CONCLUSIONS: Irrespective of ideal weight at baseline, weight gain was nearly universal. Weight ideals were shifted upward over time. PMID- 26841236 TI - Modulation of afferent nerve activity by prostaglandin E2 upon urinary bladder distension in rats. AB - NEW FINDINGS: What is the central question of this study? It has been widely assumed that C fibres innervating the bladder are mainly excited in overactive bladder syndrome. However, it remains unclear whether Adelta fibres are also activated in pathological conditions. What is the main finding and its importance? We found that a certain population of Adelta fibres, which become active specifically at a bladder pressure of more than 15 cmH2 O in normal conditions, showed increased excitability in conditions of prostaglandin E2 induced overactive bladder. This result suggests that a certain population of Adelta fibres, together with C fibres, triggers pathophysiological activity. In overactive bladder syndrome, afferent C fibres innervating the bladder show an increased activity level. However, it remains unclear whether all C fibres are highly activated and whether Adelta fibres, the other type of bladder afferent fibre, are also involved in pathological conditions. To address these questions, we analysed the relationship between bladder pressure and single-unit firing patterns of afferent nerves in the left L6 dorsal roots in living rats. The recorded fibres were classified as Adelta fibres or C fibres based on the response to 0.3 MUm tetrodotoxin. Certain populations of both Adelta fibres and C fibres were activated at bladder pressures below 15 cmH2 O (classified as low threshold fibres), indicating their potential contribution to detection of normal bladder filling. Intravesical administration of prostaglandin E2 (PGE2 ) induced hyperexcitation in approximately half of such C fibres, whereas the activity patterns of low-threshold Adelta fibres were unchanged. All fibres, regardless of type, which were almost silent in control conditions (classified as high threshold fibres), were activated by application of PGE2 . Notably, the firing patterns of Adelta fibres, rather than C fibres, were highly time locked to PGE2 induced micro-oscillation of bladder pressure. These modulatory effects of PGE2 on Adelta fibres and C fibres might trigger pathophysiological activity together in overactive bladder syndrome. PMID- 26841237 TI - Construction of Heteroacenes with Fused Thiophene and Pyrrole Rings via the Fischer Indolization Reaction. AB - A convenient approach to ladder-type 6H-benzo[4',5']thieno[2',3':4,5]thieno[3,2 b]indoles bearing various substituents in both terminal benzene rings has been developed. The protocol suggested for preparing these N,S-heteroacenes is based on using easily available reagents, such as cinnamic acids and arylhydrazines, which can be involved in the Fischer indole synthesis, as the key step. A similar condensed system of 12H benzo[4",5"]thieno[2",3":4',5']thieno[2',3':4,5]thieno[3,2-b]indole, bearing six rings, has also been obtained. PMID- 26841235 TI - Somato-dendritic Synaptic Plasticity and Error-backpropagation in Active Dendrites. AB - In the last decade dendrites of cortical neurons have been shown to nonlinearly combine synaptic inputs by evoking local dendritic spikes. It has been suggested that these nonlinearities raise the computational power of a single neuron, making it comparable to a 2-layer network of point neurons. But how these nonlinearities can be incorporated into the synaptic plasticity to optimally support learning remains unclear. We present a theoretically derived synaptic plasticity rule for supervised and reinforcement learning that depends on the timing of the presynaptic, the dendritic and the postsynaptic spikes. For supervised learning, the rule can be seen as a biological version of the classical error-backpropagation algorithm applied to the dendritic case. When modulated by a delayed reward signal, the same plasticity is shown to maximize the expected reward in reinforcement learning for various coding scenarios. Our framework makes specific experimental predictions and highlights the unique advantage of active dendrites for implementing powerful synaptic plasticity rules that have access to downstream information via backpropagation of action potentials. PMID- 26841238 TI - Megavoltage quality control, resources and demand: a pragmatic review. AB - OBJECTIVE: Satisfactory radiotherapy treatment requires quality control (QC) of the equipment as well as patient-specific checks. Increased complexity and extended use of equipment plus greater demand for complex treatment has brought pressure on QC resources. The benefits of integrating patient-specific checks and QC and the efficient use of resources is examined. METHODS: A non-linear model for the probability of undetected machine failure is proposed which enables the comparative efficiency of resource to be assessed. Benefits of adopting an integrated view of patient-specific and treatment machine QC is considered, considering performance tolerance levels in the context of measurement uncertainty and patient-specific tolerances. RESULTS: Essential, machine-only QC is identified. A realistic approach to equipment-only QC is identified for 70% efficient use of resources and a relationship established to determine resource required for a QC programme. Integration of patient-specific and equipment QC is shown to half the resource required for equipment QC. CONCLUSION: Increasing benefit from QC requires greater resource, working at lower efficiency. A pragmatic approach is having guaranteed checks supplemented with additional, non guaranteed checks performed within an integrated approach to machine- and patient specific QC, bearing in mind the occasions when machine-only QC is essential. ADVANCES IN KNOWLEDGE: The work reveals on a quantitative basis a rational approach to accommodating the QC requirements for safe and effective treatment. PMID- 26841239 TI - Sympathetic denervation facilitates L-type Ca2+ channel activation in renal but not in mesenteric resistance arteries. AB - OBJECTIVES: Sympathetic denervation enhances agonist-induced vasoconstriction. This effect may involve altered function of signaling mechanisms such as Rho kinase (Rock) and L-type Ca channels downstream from vasoconstrictor receptors. We tested if enhanced Rock and L-type calcium channel activation contribute to exaggerated norepinephrine-induced vasoconstrictions in renal and mesenteric resistance arteries after sympathectomy. METHODS: Rats underwent neonatal sympathectomy or sham sympathectomy. Resistance arteries were investigated by small vessel myography. Vascular Rock and L-type Ca channel expression as well as Rock activation were investigated by quantitative real-time PCR and Western blot. Vascular smooth muscle cell (VSMC) membrane potential was recorded with microelectrodes. RESULTS: Sympathetic denervation enhanced norepinephrine sensitivity in renal and mesenteric arteries. Both, Rock inhibition or L-type Ca inhibition shifted the norepinephrine concentration-response curve to the right. This effect was more pronounced in renal than in mesenteric arteries from sympathectomized vs. sham-sympathectomized animals. The L-type Ca channel activator S-(-)-BayK8644 elicited strong vasoconstrictions only in renal arteries from sympathectomized rats. Rock activity and L-type Ca channel alpha-subunit expression were similar in renal arteries from sympathectomized and sham sympathectomized animals. VSMC membrane potential was -57.5 +/- 2.0 and -64.3 +/- 0.3 mV (P < 0.01), respectively, in renal arteries from sympathectomized and from sham-sympathectomized rats. Depolarization enhanced and KATP channel activation abolished S-(-)-BayK8644-induced contractions in renal arteries from sympathectomized rats. CONCLUSION: Sympathetic denervation enhances L-type Ca channel-dependent signaling in renal but not in mesenteric arteries. This effect may be partly explained by the decreased VSMC membrane potential in denervated renal arteries. PMID- 26841240 TI - Protective role of sulphoraphane against vascular complications in diabetes. AB - Context Diabetes is a global health challenge. Although large prospective clinical trials have shown that intensive control of blood glucose or blood pressure reduces the risk for development and progression of vascular complications in diabetes, a substantial number of diabetic patients still experience renal failure and cardiovascular events, which could account for disabilities and high mortality rate in these subjects. Objective Sulphoraphane is a naturally occurring isothiocyanate found in widely consumed cruciferous vegetables, such as broccoli, cabbage and Brussels sprouts, and an inducer of phase II antioxidant and detoxification enzymes with anticancer properties. We reviewed here the protective role of sulphoraphane against diabetic vascular complications. Methods In this review, literature searches were undertaken in Medline and in CrossRef. Non-English language articles were excluded. Keywords [sulphoraphane and (diabetes, diabetic nephropathy, diabetic retinopathy, diabetic neuropathy, diabetic complications, vascular, cardiomyocytes, heart or glycation)] have been used to select the articles. Results There is accumulating evidence that sulphoraphane exerts beneficial effects on vascular damage in both cell culture and diabetic animal models via antioxidative properties. Furthermore, we have recently found that sulphoraphane inhibits in vitro formation of advanced glycation end products (AGEs), suppresses the AGE-induced inflammatory reactions in rat aorta by reducing receptor for AGEs (RAGE) expression and decreases serum levels of AGEs in humans. Conclusion These findings suggest that blockade of oxidative stress and/or the AGE-RAGE axis by sulphoraphane may be a novel therapeutic strategy for preventing vascular complications in diabetes. PMID- 26841243 TI - FGFR2 splice site mutations in Crouzon and Pfeiffer syndromes: two novel variants. PMID- 26841241 TI - MYO3A Causes Human Dominant Deafness and Interacts with Protocadherin 15-CD2 Isoform. AB - Hereditary hearing loss (HL) is characterized by both allelic and locus genetic heterogeneity. Both recessive and dominant forms of HL may be caused by different mutations in the same deafness gene. In a family with post-lingual progressive non-syndromic deafness, whole-exome sequencing of genomic DNA from five hearing impaired relatives revealed a single variant, p.Gly488Glu (rs145970949:G>A) in MYO3A, co-segregating with HL as an autosomal dominant trait. This amino acid change, predicted to be pathogenic, alters a highly conserved residue in the motor domain of MYO3A. The mutation severely alters the ATPase activity and motility of the protein in vitro, and the mutant protein fails to accumulate in the filopodia tips in COS7 cells. However, the mutant MYO3A was able to reach the tips of organotypic inner ear culture hair cell stereocilia, raising the possibility of a local effect on positioning of the mechanoelectrical transduction (MET) complex at the stereocilia tips. To address this hypothesis, we investigated the interaction of MYO3A with the cytosolic tail of the integral tip-link protein protocadherin 15 (PCDH15), a core component of MET complex. Interestingly, we uncovered a novel interaction between MYO3A and PCDH15 shedding new light on the function of myosin IIIA at stereocilia tips. PMID- 26841244 TI - Role of selection and gene flow in population differentiation at the edge vs. interior of the species range differing in climatic conditions. AB - Evaluating the relative importance of neutral and adaptive processes as determinants of population differentiation across environments is a central theme of evolutionary biology. We applied the QST-FST comparison flanked by a direct test for local adaptation to infer the role of climate-driven selection and gene flow in population differentiation of an annual grass Avena sterilis in two distinct parts of the species range, edge and interior, which represent two globally different climates, desert and Mediterranean. In a multiyear reciprocal transplant experiment, the plants of desert and Mediterranean origin demonstrated home advantage, and population differentiation in several phenotypic traits related to reproduction exceeded neutral predictions, as determined by comparisons of QST values with theoretical FST distributions. Thus, variation in these traits likely resulted from local adaptation to desert and Mediterranean environments. The two separate common garden experiments conducted with different experimental design revealed that two population comparisons, in contrast to multi-population comparisons, are likely to detect population differences in virtually every trait, but many of these differences reflect effects of local rather than regional environment. We detected a general reduction in neutral (SSR) genetic variation but not in adaptive quantitative trait variation in peripheral desert as compared with Mediterranean core populations. On the other hand, the molecular data indicated intensive gene flow from the Mediterranean core towards desert periphery. Although species range position in our study (edge vs. interior) was confounded with climate (desert vs. Mediterranean), the results suggest that the gene flow from the species core does not have negative consequences for either performance of the peripheral plants or their adaptive potential. PMID- 26841242 TI - Vibratory Urticaria Associated with a Missense Variant in ADGRE2. AB - Patients with autosomal dominant vibratory urticaria have localized hives and systemic manifestations in response to dermal vibration, with coincident degranulation of mast cells and increased histamine levels in serum. We identified a previously unknown missense substitution in ADGRE2 (also known as EMR2), which was predicted to result in the replacement of cysteine with tyrosine at amino acid position 492 (p.C492Y), as the only nonsynonymous variant cosegregating with vibratory urticaria in two large kindreds. The ADGRE2 receptor undergoes autocatalytic cleavage, producing an extracellular subunit that noncovalently binds a transmembrane subunit. We showed that the variant probably destabilizes an autoinhibitory subunit interaction, sensitizing mast cells to IgE independent vibration-induced degranulation. (Funded by the National Institutes of Health.). PMID- 26841245 TI - Spectroscopic signatures of ligand field states in {Ru(II)(imine)} complexes. AB - Ligand field (LF) states have been present in discussions on the photophysics and photochemistry of ruthenium-iminic chromophores for decades, although there is very little documented direct evidence of them. We studied the picosecond transient absorption (TA) spectroscopy of four {Ru(II)(imine)} complexes that respond to the formula trans-[Ru(L)4(X)2], where L is either pyridine (py) or 4 methoxypyridine (MeOpy) and X is either cyanide or thiocyanate. Dicyano compounds behave as most ruthenium polypyridines and their LF states remain silent. In contrast, in the dithiocyanate complexes we found clear spectroscopic evidence of the participation of LF states in the MLCT decay pathway. These states are of donor and acceptor character simultaneously and this is manifested in the presence of MLCT and LMCT transient absorption bands of similar energy. Spectroelectrochemical techniques supported the interpretation of the absorption features of MLCT states, and DFT methods helped to assign their spectroscopic signatures and provided strong evidence on the nature of LF states. PMID- 26841246 TI - Synthesis, Polymorphism, and Insecticidal Activity of Methyl 4-(4-chlorophenyl)-8 iodo-2-methyl-6-oxo-1,6-dihydro-4H-pyrimido[2,1-b]quinazoline-3-Carboxylate Against Anopheles arabiensis Mosquito. AB - Mosquitoes are the major vectors of pathogens and parasites including those causing malaria, the most deadly vector-borne disease. The negative environmental effects of most synthetic compounds combined with widespread development of insecticide resistance encourage an interest in finding and developing alternative products against mosquitoes. In this study, pyrimido[2,1 b]quinazoline derivative DHPM3 has been synthesized by three-step chemical reaction and screened for larvicide, adulticide, and repellent properties against Anopheles arabiensis, one of the dominant vectors of malaria in Africa. The title compound emerged as potential larvicide agent for further research and development, because it exerted 100% mortality, while adulticide activity was considered moderate. PMID- 26841247 TI - Prenatal reflex DNA screening for Down syndrome: enhancing the screening performance of the initial first trimester test. AB - OBJECTIVE: To estimate the effect of adding three biochemical markers (alphafetoprotein, inhibin-A, and placental growth factor) and two ultrasound markers (ductus venosus pulsatility index and nasal bone examination) to enhance the initial Combined test in prenatal reflex DNA screening for Down syndrome. METHODS: Published data were used to estimate screening performance [detection rates (DRs) and false-positive rates (FPRs)] of reflex DNA screening according to the additional markers used, the proportion of women with the highest initial test risks reflexed to DNA testing and the gestational age at the time of blood collection. RESULTS: If 10% of women are reflexed, the addition of the three biochemical markers to the Combined test increases the DR from 90.8% to 92.3% (FPR 0.025% to 0.027%) with markers measured at 11 completed weeks' gestation. With markers measured at 13 completed weeks' gestation the DR increases from 87.7% to 95.2% (FPRs both 0.027%). The further addition of the two ultrasound markers increases the DR to 96.8% and 97.5% at 11 and 13 weeks' respectively (FPR to 0.024% and 0.022% respectively). CONCLUSION: Adding the specified markers to the Combined test can maintain or improve screening performance with a lower proportion of women reflexed. Our results can be used to determine the most cost effective reflex DNA screening policy. (c) 2016 John Wiley & Sons, Ltd. PMID- 26841248 TI - Characterisation of potato crisp effective porosity using micro-CT. AB - BACKGROUND: The effective porosity is an important quantitative parameter for food products that has a significant effect on taste and quality. It is challenging to quantify the apparent porosity of fried potato crisps as they have a thin irregularly shaped cross section containing oil and water. This study uses a novel micro-CT technique to determine the solid volume fraction and hence the effective porosity of three types of potato crisps: standard continuously fried crisps, microwaved crisps, and continuously fried 'kettle' crisps. RESULTS: It was found that continuously fried kettle crisps had the lowest effective porosity at 0.54, providing the desired crunchy taste and lower oil contents. Crisps produced using a microwave process designed to mimic the dehydration process of standard continuous fried crisps had an effective porosity of 0.65, which was very similar to the effective porosity of 0.63 for standard continuously fried crisps. The results were supported by the findings of a forced preference consumer test. CONCLUSION: The effective porosity affects the product taste and is therefore a critical parameter. This study shows that micro-CT analysis can be used to characterise the change in effective porosity of a thin irregularly shaped food product, caused by a change of cooking procedure. (c) 2016 Society of Chemical Industry. PMID- 26841250 TI - Contemporary retinal imaging techniques in diabetic retinopathy: a review. AB - Over the last decade, there has been an expansion of imaging modalities available to clinicians to diagnose and monitor the treatment and progression of diabetic retinopathy. Recently, advances in image technologies related to OCT and OCT angiography have enabled improved visualization and understanding of this disease. In this review, we will describe the use of imaging techniques such as colour fundus photography, fundus autofluorescence, fluorescein angiography, infrared reflectance imaging, OCT, OCT-Angiography and techniques in adaptive optics and hyperspectral imaging in the diagnosis and management of diabetic retinopathy. PMID- 26841249 TI - A New G-Quadruplex with Hairpin Loop Immediately Upstream of the Human BCL2 P1 Promoter Modulates Transcription. AB - The abnormal overexpression of the BCL2 gene is associated with many human tumors. We found a new 28-mer G-quadruplex-forming sequence, P1G4, immediately upstream of the human BCL2 gene P1 promoter. The P1G4 is shown to be a transcription repressor using a promoter-driven luciferase assay; its inhibitory effect can be markedly enhanced by the G-quadruplex-interactive compound TMPyP4. G-quadruplex can readily form in the P1G4 sequence under physiological salt condition as shown by DMS footprinting. P1G4 and previously identified Pu39 G quadruplexes appear to form independently in adjacent regions in the BCL2 P1 promoter. In the extended BCL2 P1 promoter region containing both Pu39 and P1G4, P1G4 appears to play a more dominant role in repressing the transcriptional activity. Using NMR spectroscopy, the P1G4 G-quadruplex appears to be a novel dynamic equilibrium of two parallel structures, one regular with two 1-nt loops and a 12-nt middle loop and another broken-strand with three 1-nt loops and a 11 nt middle loop; both structures adopt a novel hairpin (stem-loop duplex) conformation in the long loop. The dynamic equilibrium of two closely related structures and the unique hairpin loop conformation are specific to the P1G4 sequence and distinguish the P1G4 quadruplex from other parallel structures. The presence of P1G4 and Pu39 in adjacent regions of the BCL2 P1 promoter suggests a mechanism for precise regulation of BCL2 gene transcription. The unique P1G4 G quadruplex may provide a specific target for small molecules to modulate BCL2 gene transcription. PMID- 26841251 TI - Survey of partner notification practices for sexually transmissible infections in the United States. AB - Background Partner notification (PN) for sexually transmissible infections (STIs) is a vital STI control method. The most recent evaluation of PN practices in the United States, conducted in 1999, indicated that few STI patients were offered PN services. The objectives of this study were to obtain a preliminary understanding of the current provision of PN services in HIV/STI testing sites throughout the US and to determine the types of PN services available. METHODS: A convenience sample of 300 randomly selected testing sites was contacted to administer a phone survey about PN practices. These sites were from a large database maintained by the Centers for Disease Control and Prevention. Sites were eligible to participate if they provided testing services for chlamydia, gonorrhoea, HIV or syphilis and were not hospitals or Planned Parenthood locations. RESULTS: Of the 300 eligible sites called, 79 sites were successfully reached, of which 74 agreed to participate, yielding a response rate of 24.7% and a cooperation rate of 93.7%. Most surveyed testing sites provided some form of PN service (anonymous or non-anonymous) on site or through an affiliate for chlamydia (100%), gonorrhoea (97%), HIV (91%) and syphilis (96%) infection. Anonymous PN services were available at 67-69% of sites. Only 6-9% of sites offered Internet-based PN services. CONCLUSIONS: Most surveyed testing sites currently offer some type of PN service for chlamydia, gonorrhoea, HIV or syphilis infection. However, approximately one-third of surveyed sites do not offer anonymous services. Novel, Internet-based methods may be warranted to increase the availability of anonymous services. PMID- 26841252 TI - Implantable central venous access device in infants: Long-term results. AB - BACKGROUND: The management of central venous access device (CVAD) is extremely difficult in babies and small infants (BSI). We therefore compared the long-term results and complications of CVAD in BSI with those in children. METHODS: One hundred and twenty patients were divided into two groups as follows: age <1 year or weight <10 kg (group A; 25 patients); and age ?1 year and weight ?10 kg (group B; 95 patients). The clinical results were retrospectively compared between the groups. RESULTS: Mean age and weight were 12.5 +/- 5.9 months and 8.2 +/- 1.2 kg in group A, and 78.8 +/- 58.9 months and 20.9 +/- 13.6 kg in group B. Operation time was 57 +/- 29 min in group A and 52 +/- 21 min in group B (P = 0.38). The catheter was advanced with difficulty into the central vein in five and in 16 patients (P = 0.77), and surgical complications occurred in one and in seven patients in groups A and B, respectively (P > 0.99). The CVAD remained in place for 627 +/- 494 and 550 +/- 414 days (P = 0.47) and was removed before treatment completion in five and in 14 patients in groups A and B, respectively (P = 0.54). CONCLUSION: The clinical results for CVAD in BSI did not differ from those in children. CVAD are useful and safe for the treatment of BSI with serious diseases. PMID- 26841253 TI - Expression of stem cell-regulating miRNAs in oral cavity and oropharynx squamous cell carcinoma. AB - BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common tumor worldwide and is histologically heterogeneous. Studies have demonstrated the presence of stem cell markers in HNSCC, and microRNAs (miRNAs) have emerged as powerful regulators of differentiation, controlling the self renewal of stem cells. miRNAs are non-coding RNA molecules that regulate gene expression post-transcriptionally. Many miRNAs have been described as regulators of stem cells in different types of cancer. METHODS: We have analyzed the expression of let-7a, miR-34, miR-125b, miR-138, miR-145, miR-183, miR-200b, miR 203, and miR-205 by real-time RT-PCR (qPCR), in 35 oral cavity and oropharynx squamous cell carcinoma (SCC) samples and 10 non-neoplastic oral mucosa controls, to determine possible associations between the expression of these miRNAs and clinical and pathological features of these tumors. RESULTS: We observed downregulation of miR-200b and miR-203 in 60.0% and 71.4% of the samples, respectively. Upregulation of miR-138 and miR-183 was observed in 50.0% of the samples. Downregulation of let-7a was associated with perineural invasion. Upregulation of miR-138, miRNA-145, and miR-205 was associated with advanced tumor stages, vascular invasion, and lymph node metastasis, respectively. CONCLUSIONS: Our study provides evidence of the expression of miRNAs associated with stem cell regulation in oral cavity and oropharynx SCC and the association of these miRNAs with clinical and pathological features of these tumors. PMID- 26841254 TI - Role of lectin microarrays in cancer diagnosis. AB - The majority of cell differentiation associated tumor markers reported to date are either glycoproteins or glycolipids. Despite there being a large number of glycoproteins reported as candidate markers for various cancers, only a handful are approved by the US Food and Drug Administration. Lectins, which bind to the glycan part of the glycoproteins, can be exploited to identify aberrant glycosylation patterns, which in turn would help in enhancing the specificity of cancer diagnosis. Although conventional techniques such as HPLC and MS have been instrumental in performing the glycomic analyses, these techniques lack multiplexity. Lectin microarrays have proved to be useful in studying multiple lectin-glycan interactions in a single experiment and, with the advances made in the field, hold a promise of enabling glycomic profiling of cancers in a fast and efficient manner. PMID- 26841255 TI - Comparison of the Artus RotorGene and COBAS Ampliprep/COBAS TaqMan Platforms for the Detection of Cytomegalovirus: Experience of a Tertiary Care Center. AB - INTRODUCTION: Cytomegalovirus (CMV) is a member of the Herpesviruses family. CMV infection rarely causes serious disease in otherwise healthy individuals, however, infection/reactivation among immunocompromised patients, including those undergoing hematopoietic stem cell transplantation (HSCT), can be critical and is associated with high rates of morbidity and mortality. The detection of CMV in blood using real-time polymerase chain reaction (qPCR) methods is the most sensitive and specific technique providing for a well-determined preemptive treatment cutoff. AIM: This study compares the performance of two new CMV qPCR platforms, COBAS((r)) Ampliprep/COBAS((r)) TaqMan((r)) (Roche Molecular Diagnostics) and Artus RotorGene (QIAGEN). METHODS: A total of 99 patients referred for CMV testing at AUBMC were tested using the Artus CMV RG PCR kit and the COBAS AmpliPrep/COBAS TaqMan CMV kit as per the manufacturers' recommendations. RESULTS: The difference between the two methods was within the allowable error for 97 out of 99 specimens (98%), with a correlation coefficient r = 0.80. CONCLUSION: The Artus CMV RG PCR Kit and the COBAS AmpliPrep/COBAS TaqMan CMV kit are both acceptable assays that can be used for the sensitive detection and quantitation of CMV mainly in peripheral blood specimens. PMID- 26841256 TI - Quality and Reporting Accuracy of Phase 1 Drug Radiation Clinical Trials. PMID- 26841257 TI - Editors' Choice. PMID- 26841259 TI - Emergence of Magnetic States in Pr2Fe(4-x)Co(x)Sb5 (1 < x < 2.5). AB - Single crystals of Pr2Fe(4-x)Co(x)Sb5 (1 < x < 2.5) were grown from a Bi flux and characterized by X-ray diffraction. The compounds adopt the La2Fe4Sb5 structure type (I4/mmm). The structure of Pr2Fe(4-x)Co(x)Sb5 (1 < x < 2.5) contains a network of transition metals forming isosceles triangles. The x ~ 1 analogue is metallic and exhibits a magnetic transition at T1 ~ 25 K. The magnetic moment obtained from the Curie-Weiss fit is 11.49(4) MU(B), which is larger than the spin-only Pr(3+) moment. The x ~ 2 analogue orders magnetically at T1 ~ 80 and T2 ~ 45 K. This is the first case of the substitution of Co into the La2Fe4Sb5 structure type, evidenced by the increased concentration of dopant with decreased lattice parameters coupled with a change in the transition temperature with a change in the cobalt concentration. The added complexity in the magnetic behavior of the x ~ 1 and 2 analogues indicates that the increased concentration of Co invokes an additional magnetic contribution of the transition metal in the sublattice. Furthermore, X-ray photoelectron spectroscopy measurements support the change in the oxidation states of transition metals with increasing cobalt concentration. PMID- 26841258 TI - A Longitudinal Study of Skeletal Histomorphometry at 6 and 24 Months Across Four Bone Envelopes in Postmenopausal Women With Osteoporosis Receiving Teriparatide or Zoledronic Acid in the SHOTZ Trial. AB - Previously, we reported the effects of teriparatide (TPTD) and zoledronic acid (ZOL) on bone formation based on biochemical markers and bone histomorphometry of the cancellous envelope at month 6 in postmenopausal women with osteoporosis who participated in the 12-month primary Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronic Acid Therapy (SHOTZ) study. Patients were eligible to enter a 12-month extension on their original treatment regimen: TPTD 20 MUg/day (s.c. injection) or ZOL 5 mg/year (i.v. infusion). A second biopsy was performed at month 24. Here we report longitudinal changes between and within each treatment group in the cancellous, endocortical, intracortical, and periosteal bone envelopes in patients with evaluable biopsies at months 6 and 24 (paired data set: TPTD, n = 10; ZOL, n = 9). Between-group differences are also reported in the larger set of patients with evaluable biopsies at month 6 (TPTD, n = 28; ZOL, n = 30). Data from the cancellous envelope at month 6 or month 24 provided a reference to compare differences across envelopes within each treatment group. The 24-month results extend our earlier report that TPTD and ZOL possess different tissue-level mechanisms of action. Moreover, these differences persisted for at least 2 years in all four bone envelopes. Few longitudinal differences were observed within or across bone envelopes in ZOL-treated patients, suggesting that the low bone formation indices at month 6 persisted to month 24. Conversely, the magnitude of the effect of TPTD on bone formation varied across individual envelopes: median values for mineralizing surface (MS/BS) and bone formation rate (BFR/BS) at month 6 were approximately 3-fold to 5-fold higher in the endocortical and intracortical envelopes compared to the cancellous envelope. Although MS/BS and BFR/BS declined in these envelopes at month 24, median values continued to exceed, or were not significantly different from, those in the cancellous envelope. This study demonstrates for the first time that bone formation indices are higher with TPTD treatment than with ZOL in all four bone envelopes and the difference persists for at least 2 years. Moreover, the magnitude of the effect of TPTD in cortical bone remains robust at 24 months. (c) 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR). PMID- 26841260 TI - Nitric Oxide Chemical Donor Affects the Early Phases of In Vitro Wound Healing Process. AB - An artificial wound in a confluent monolayer of human keratinocyte HaCaT cells or mouse embryo fibroblast Swiss NIH 3T3 cells was used to analyze the effects of the nitric oxide (NO) chemical donor, S-nitroso-N-acetylpenicillamine (SNAP). SNAP exposure promoted an enhanced rate of wound closure and accelerated motility of both keratinocytes and fibroblasts compared to control cells. The wounded monolayer cultures of HaCaT and NIH 3T3 cells, treated with or without SNAP, were monitored under a phase contrast microscope. Structural and ultrastructural modifications were analyzed by scanning electron microscopy (SEM). The images were captured by a digital camera at different time points (0-28 h) and the wound area was analyzed through software included in Matlab(r). As early as 15 min, SNAP induced significant cytoskeletal remodeling, as shown by immunostaining (phalloidin-labelling), which in turn was associated with increased filopodium number and length rise. NO donor treatment also induced overexpression of Ki-67 protein, a typical marker of cell proliferation, as shown by immunostaining. Both SNAP-induced migration and proliferation were antagonized by the NO-sensitive GC inhibitor 1H-[1,2,4]oxadiazolo[-4,3-a]quinoxalin-1-one (ODQ), which suggests activation of the NO/cGMP signalling cascade in the observed SNAP-induced effects in the early stages of the healing process. Moreover, we provide evidence that PPAR-beta antagonist (GSK0660) may interfere with NO-mediated wound healing process. J. Cell. Physiol. 231: 2185-2195, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26841261 TI - Biological Evaluation of Ferrocenyl Olefins: Cancer Cell Growth Inhibition, ROS Production, and Apoptosis Activity. AB - The antiproliferative effects of various ferrocenyl olefins were evaluated against the cell lines MCF-7 (human breast cancer cells), DLD-1 (human colon adenocarcinoma cells), HUVEC (human umbilical vein endothelial cells), and A549 (human lung carcinoma cells), using the MTT test. IC50 values were determined. Compounds 8, 9, 11, and 12 with high antiproliferative activity were tested for their reactive oxygen species (ROS) production, and cell cycle analysis was performed on A549 cells. The results show that these compounds might perform their antiproliferative activity through inducing ROS generation, apoptosis induction, and cell cycle arrest. PMID- 26841262 TI - Stabilisation times after transitions to standing from different working postures. AB - Transitioning to standing after maintaining working postures may result in imbalance and could elicit a fall. The objective of this study was to quantify the magnitude of imbalance using a stabilisation time metric. Forty-five male participants completed three replications of conditions created by one of four working postures (bent at waist, squat, forward kneel, reclined kneel) and three durations within posture. Participants transitioned to quiet standing at a self selected pace. Stabilisation time, based on changes in centre of pressure velocity, was used to indicate the initiation of steady state while standing. Stabilisation time was significantly affected by static postures but not duration within posture. The largest stabilisation times resulted from transitions initiated from a bent at waist posture. The smallest were associated with the kneeling postures, which were not significantly different from each other. Findings may lead to recommendations for redesign of tasks, particularly in high risk environments such as construction. Statement of Relevance: Task performance on the jobsite often requires individuals to maintain non-erect postures. This study suggests that working posture affects stabilisation during transition to a standing position. Bending at the waist and squatting resulted in longer stabilisation times, whereas both kneeling postures evaluated resulted in greater imbalance but for a shorter duration. PMID- 26841264 TI - Metal-Organic Framework-Templated Porous Carbon for Highly Efficient Catalysis: The Critical Role of Pyrrolic Nitrogen Species. AB - Metal-free catalysts are of great importance and alternative candidates to conventional metal-based catalysts for many reactions. Herein, several types of metal-organic frameworks have been exploited as templates/precursors to afford porous carbon materials with various nitrogen dopant forms and contents, degrees of graphitization, porosities, and surface areas. Amongst these materials, the PCN-224-templated porous carbon material optimized by pyrolysis at 700 degrees C (denoted as PCN-224-700) is composed of amorphous carbon coated with well-defined graphene layers, offering a high surface area, hierarchical pores, and high nitrogen content (mainly, pyrrolic nitrogen species). Remarkably, as a metal-free catalyst, PCN-224-700 exhibits a low activation energy and superior activity to most metallic catalysts in the catalytic reduction of 4-nitrophenol to 4 aminophenol. Theoretical investigations suggest that the content and type of the nitrogen dopant play crucial roles in determining the catalytic performance and that the pyrrolic nitrogen species makes the dominant contribution to this activity, which explains the excellent efficiency of the PCN-224-700 catalyst well. PMID- 26841263 TI - Persistence, distribution, and impact of distinctly segmented microparticles on cochlear health following in vivo infusion. AB - Delivery of pharmaceuticals to the cochleae of patients with auditory dysfunction could potentially have many benefits from enhancing auditory nerve survival to protecting remaining sensory cells and their neuronal connections. Treatment would require platforms to enable drug delivery directly to the cochlea and increase the potential efficacy of intervention. Cochlear implant recipients are a specific patient subset that could benefit from local drug delivery as more candidates have residual hearing; and since residual hearing directly contributes to post-implantation hearing outcomes, it requires protection from implant insertion-induced trauma. This study assessed the feasibility of utilizing microparticles for drug delivery into cochlear fluids, testing persistence, distribution, biocompatibility, and drug release characteristics. To allow for delivery of multiple therapeutics, particles were composed of two distinct compartments; one containing polylactide-co-glycolide (PLGA), and one composed of acetal-modified dextran and PLGA. Following in vivo infusion, image analysis revealed microparticle persistence in the cochlea for at least 7 days post infusion, primarily in the first and second turns. The majority of subjects maintained or had only slight elevation in auditory brainstem response thresholds at 7 days post-infusion compared to pre-infusion baselines. There was only minor to limited loss of cochlear hair cells and negligible immune response based on CD45+ immunolabling. When Piribedil-loaded microparticles were infused, Piribedil was detectable within the cochlear fluids at 7 days post-infusion. These results indicate that segmented microparticles are relatively inert, can persist, release their contents, and be functionally and biologically compatible with cochlear function and therefore are promising vehicles for cochlear drug delivery. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1510-1522, 2016. PMID- 26841265 TI - Health Insurance Dynamics: Methodological Considerations and a Comparison of Estimates from Two Surveys. AB - OBJECTIVE: To highlight key methodological issues in studying insurance dynamics and to compare estimates across two commonly used surveys. DATA SOURCES/STUDY SETTING: Nonelderly uninsured adults and children sampled between 2001 and 2011 in the Medical Expenditure Panel Survey and the Survey of Income and Program Participation. STUDY DESIGN: We utilized nonparametric Kaplan-Meier methods to estimate quantiles (25th, 50th, and 75th percentiles) in the distribution of uninsured spells. We compared estimates obtained across surveys and across different methodological approaches to address issues like attrition, seam bias, censoring and truncation, and survey weighting method. DATA COLLECTION/EXTRACTION METHODS: All data were drawn from publicly available household surveys. PRINCIPAL FINDINGS: Estimated uninsured spell durations in the MEPS were longer than those observed in the SIPP. There were few changes in spell durations between 2001 and 2011, with median durations of 14 months among adults and 5-7 months among children in the MEPS, and 8 months (adults) and 4 months (children) in the SIPP. CONCLUSIONS: The use of panel survey data to study insurance dynamics presents a unique set of methodological challenges. Researchers should consider key analytic and survey design trade-offs when choosing which survey can best suit their research goals. PMID- 26841266 TI - Salares versus coastal ecotypes of quinoa: Salinity responses in Chilean landraces from contrasting habitats. AB - Quinoa (Chenopodium quinoa Willd.) is a highly salt-tolerant species subdivided into five ecotypes and exhibiting broad intra-specific differences in tolerance levels. In a greenhouse study, Chilean landraces belonging either to the salares (R49) or coastal lowlands (VI-1, Villarrica) ecotype with contrasting agro ecological origins were investigated for their responses to high salinity. The effects of two levels of salinity, 100 (T1) and 300 (T2) mM NaCl, on plant growth and on some physiological parameters were measured. Leaf and root Na(+) accumulation differed among landraces. T2 reduced growth and seed yield in all landraces with maximum inhibition relative to controls in R49. Salinity negatively affected chlorophyll and total polyphenol content (TPC) in VI-1 and Villarrica but not R49. Germination on saline or control media of seeds harvested from plants treated or not with NaCl was sometimes different; the best performing landrace was R49 insofar as 45-65% of seeds germinated on 500 mM NaCl-containing medium. In all landraces, average seedling root length declined strongly with increasing NaCl concentration, but roots of R49 were significantly longer than those of VI-1 and Villarrica up to 300 mM NaCl. Salt caused increases in seed TPC relative to controls, but radical scavenging capacity was higher only in seeds from T2 plants of R49. Total SDS-extractable seed proteins were resolved into distinct bands (10-70 kDa) with some evident differences between landraces. Salt induced changes in protein patterns were landrace-specific. The responses to salinity of the salares landrace are discussed in relation to its better adaptation to an extreme environment. PMID- 26841267 TI - Investigation of the effect of genotype and agronomic conditions on metabolomic profiles of selected strawberry cultivars with different sensitivity to environmental stress. AB - Strawberry is one of the most economically important and widely cultivated fruit crops across the world, so that there is a growing need to develop new analytical methodologies for the authentication of variety and origin, as well as the assessment of agricultural and processing practices. In this work, an untargeted metabolomic strategy based on gas chromatography mass spectrometry (GC-MS) combined with multivariate statistical techniques was used for the first time to characterize the primary metabolome of different strawberry cultivars and to study metabolite alterations in response to multiple agronomic conditions. For this purpose, we investigated three varieties of strawberries with different sensitivity to environmental stress (Camarosa, Festival and Palomar), cultivated in soilless systems using various electrical conductivities, types of coverage and substrates. Metabolomic analysis revealed significant alterations in primary metabolites between the three strawberry cultivars grown under different crop conditions, including sugars (fructose, glucose), organic acids (malic acid, citric acid) and amino acids (alanine, threonine, aspartic acid), among others. Therefore, it could be concluded that GC-MS based metabolomics is a suitable tool to differentiate strawberry cultivars and characterize metabolomic changes associated with environmental and agronomic conditions. PMID- 26841268 TI - Patients' experience of colonoscopy in the English Bowel Cancer Screening Programme. AB - BACKGROUND AND STUDY AIMS: Understanding patients' experience of screening programs is crucial for service improvement. The English Bowel Cancer Screening Programme (BCSP) aims to achieve this by sending out questionnaires to all patients who undergo a colonoscopy following an abnormal fecal occult blood test result. This study used the questionnaire data to report the experiences of these patients. PATIENTS AND METHODS: Data on patients who underwent colonoscopy between 2011 and 2012 were extracted from the BCSP database. Descriptive statistics were used to summarize key questionnaire items relating to informed choice, psychological wellbeing, physical experience, and after-effects. Multilevel logistic regression was used to test for associations with variables of interest: sex, age, socioeconomic status, colonoscopy results, and screening center performance (adenoma detection rate, cecal intubation rate, proportion of colonoscopies involving sedation). RESULTS: Data from 50,858 patients (79.3 % of those eligible) were analyzed. A majority reported a positive experience on items relating to informed choice (e. g. 95.7 % felt they understood the risks) and psychological wellbeing (e. g. 98.3 % felt they were treated with respect). However, an appreciable proportion experienced unexpected test discomfort (21.0 %) or pain at home (14.8 %). There were few notable demographic differences, although women were more likely than men to experience unexpected discomfort (25.1 % vs. 18.0 %; P < 0.01) and pain at home (18.2 % vs. 12.3 %; P < 0.01). No associations with center-level variables were apparent. CONCLUSIONS: Colonoscopy experience was generally positive, suggesting high satisfaction with the BCSP. Reported pain and unexpected discomfort were more negative than most other outcomes (particularly for women); measures to improve this should be considered. PMID- 26841270 TI - Pulmonary Edema Assessed by Ultrasound: Impact in Cardiology and Intensive Care Practice. AB - Pulmonary edema is a frequent condition found in adult patients hospitalized in cardiology wards and intensive care units. Ultrasonography is a diagnostic modality with a high sensitivity for the detection of extravascular lung water, visualized as B lines, and usually caused by cardiogenic or noncardiogenic pulmonary edema. This paper highlights a simple method for the assessment of patients with pulmonary edema, which allows for a differential diagnosis of its possible mechanism and contributes to therapeutic intervention guiding and monitoring. PMID- 26841269 TI - Requirements and standards facilitating quality improvement for reporting systems in gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement. AB - To develop standards for high quality in gastrointestinal (GI) endoscopy, the European Society of Gastrointestinal Endoscopy (ESGE) has established the ESGE Quality Improvement Committee. A prerequisite for quality assurance and improvement for all GI endoscopy procedures is state-of-the-art integrated digital reporting systems for standardized documentation of the procedures. The current paper describes the ESGE's viewpoints on the requirements for high quality endoscopy reporting systems in GI endoscopy. Recommendations 1 Endoscopy reporting systems must be electronic. 2 Endoscopy reporting systems should be integrated into hospitals' patient record systems. 3 Endoscopy reporting systems should include patient identifiers to facilitate data linkage to other data sources. 4 Endoscopy reporting systems shall restrict the use of free-text entry to a minimum, and be based mainly on structured data entry. 5 Separate entry of data for quality or research purposes is discouraged. Automatic data transfer for quality and research purposes must be facilitated. 6 Double entry of data by the endoscopist or associate personnel is discouraged. Available data from outside sources (administrative or medical) must be made available automatically. 7 Endoscopy reporting systems shall facilitate the inclusion of information on histopathology of detected lesions, patient satisfaction, adverse events, and surveillance recommendations. 8 Endoscopy reporting systems must facilitate easy data retrieval at any time in a universally compatible format. 9 Endoscopy reporting systems must include data fields for key performance indicators as defined by quality improvement committees. 10 Endoscopy reporting systems must facilitate changes in indicators and data entry fields as required by professional organizations. PMID- 26841271 TI - Correlates of health related quality of life in anorexia nervosa. AB - OBJECTIVE: We examined the association between disorder specific factors, comorbidity and health related quality of life (HRQoL) in anorexia nervosa (AN). METHOD: HRQoL was assessed using the EuroQol-5D visual analog scale (EQ-VAS) in this cross-sectional study. Three regression models were estimated to determine the association between AN subtype (restrictive vs. binge/purge), duration of the eating disorder (ED), age (adolescents vs. adults), ED pathology (EDE-Q), Body Mass Index (BMI), depressive symptoms (PHQ-9), somatic complaints (PHQ-15), anxiety (GAD-7) and EQ-VAS. RESULTS: The sample comprised 218 female AN patients (mean age = 23.3 years [SD = 8.2]; mean EQ-VAS score = 53.4 [SD = 21.4]). A lower BMI, higher levels of depressive symptoms, and somatic complaints were significantly associated with lower EQ-VAS scores. DISCUSSION: Findings of the present study suggest that BMI and comorbidity might be more relevant to HRQoL impairments in AN than age, diagnostic subtype, duration of the ED or current psychopathology. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:630 634). PMID- 26841273 TI - High-grade histology as predictor of early distant metastases and decreased disease-free survival in salivary gland cancer irrespective of tumor subtype. AB - BACKGROUND: The purpose of this study was to evaluate risk factors that influence overall survival (OS)/disease-free survival (DFS)/locoregional recurrence-free survival (LRFS), and distant metastases-free survival (DMFS) in patients with high-risk primary salivary gland carcinoma who underwent surgery and postoperative (chemo)radiotherapy with curative intention. METHODS: We reviewed data of 63 patients with high-risk primary salivary gland carcinoma in a retrospective single-center audit. RESULTS: At a median follow-up of 31 months (range, 5-145 months), cumulative OS and DFS were 91.7%, 77.6%, and 62.9%, and 82.1%, 65.6%, and 57.7%, respectively, after 1, 2, and 5 years. LRFS and DMFS were 92%, 86%, and 86%, and 83.4%, 70.4%, and 62.3% after 1, 2, and 5 years, respectively. Of all patient-related, tumor-related, and treatment-related factors, high-grade histology (G3) was the only factor in univariate and multivariate analysis that was predictive for a shorter DMFS (low/intermediate vs high-grade: 100%, 100%, and 89.4% vs 72.9%, 54.3%, and 42.8% after 1, 2, and 5 years, respectively) and a shorter DFS (low/intermediate vs high-grade: 100%, 90%, and 84.4% vs 71.2%, 50.1%, and 39.4% after 1, 2, and 5 years, respectively) and OS (low/intermediate vs high-grade: 100%, 100%, and 86.5% vs 86.5%, 63.2%, and 46.5% after 1, 2, and 5 years, respectively). CONCLUSION: High-grade tumor histology is a highly significant predictor of a shorter DMFS, OS, and DFS in salivary gland carcinoma, irrespective of histological subtype. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2041-E2048, 2016. PMID- 26841274 TI - Now how do we get them home? Outpatient care of pediatric patients on mechanical circulatory support. AB - The last five yr have been monumental for the pediatric heart failure community. In the US, the most notable has been the FDA approval of the first pediatric specific device (Berlin Heart EXCOR((r)) ; Berlin Heart, Inc., Berlin, Germany). Subsequently, the field of heart failure has gained a great deal of knowledge regarding the nuances of MCS in children. Despite FDA approval in the US, the Berlin EXCOR((r)) is only currently indicated for in-hospital use. Due to the limitations with discharge and the positive in- hospital experiences with the Berlin EXCOR((r)) , there has been an increased interest in the implantation of adult durable devices into children. While many institutions have focused their intial efforts on the first phase of care within the hospital, they are now ready to tackle the challenge of how to safely transition children to the community setting. PMID- 26841275 TI - Gate-Optimized Thermoelectric Power Factor in Ultrathin WSe2 Single Crystals. AB - We report an electric field tuning of the thermopower in ultrathin WSe2 single crystals over a wide range of carrier concentration by using electric double layer (EDL) technique. We succeeded in the optimization of power factor not only in the hole but also in the electron side, which has never been chemically accessed. The maximized values of power factor are one-order larger than that obtained by changing chemical composition, reflecting the clean nature of electrostatic doping. PMID- 26841276 TI - Should we worry about obesity in our ovarian cancer patients, too? PMID- 26841277 TI - Emotional labour and work engagement among nurses: examining perceived compassion, leadership and work ethic as stress buffers. AB - AIM: The study examined whether three resources, that is, compassion, transformational leadership and work ethic feasibility, buffer against the negative effects of emotional labour on work engagement. BACKGROUND: Emotional labour is a common job stressor among nurses, but little is known about whether certain personal and work resources buffer against it in relation to work engagement. Revealing buffers of emotional labour would help organizations to design tailored interventions. DESIGN: Cross-sectional online survey conducted in 2014. METHODS: Participants were 3466 Finnish nurses. Hypotheses were tested via hierarchical moderated regression analyses. RESULTS: Higher emotional labour related to lower engagement. Two interaction effects were found. First, work ethic feasibility buffered against emotional labour: the nurses who perceived work ethic feasibility as high in a situation of high emotional labour, scored higher on engagement compared with those nurses who in this stress situation perceived work ethic feasibility to be low. Second, high compassion was detrimental to engagement in the presence of high emotional labour. Transformational leadership did not act as a buffer but showed a positive relationship with engagement. CONCLUSION: Work ethic feasibility (being able to work according to high ethical standards) is an important resource in nursing as it protects an employee against the negative effects of emotional labour and as it also directly promotes engagement. However, compassion may not always be beneficial in nursing, especially if co-occurring with high job stress. Transformational leadership has potential to improve engagement in nursing although it may not operate as a stress buffer. PMID- 26841278 TI - Using Virtual Patients to Teach Empathy: A Randomized Controlled Study to Enhance Medical Students' Empathic Communication. AB - INTRODUCTION: Physician empathy is a complex phenomenon known to improve illness outcomes; however, few tools are available for deliberate practice of empathy. We used a virtual patient (VP) to teach empathic communication to first-year medical students. We then evaluated students' verbal empathy in a standardized patient (SP) interaction. METHODS: Seventy medical students, randomly assigned to 3 separate study groups, interacted with (1) a control VP portraying depression, (2) a VP with a backstory simulating patient shadowing, or (3) a VP able to give immediate feedback about empathic communication (empathy-feedback VP). Subsequently, the students interviewed an SP portraying a scenario that included opportunities to express empathy. All SP interviews were recorded and transcribed. The study outcomes were (1) the students' verbal response to the empathic opportunities presented by the SP, as coded by reliable assessors using the Empathic Communication Coding System, and (2) the students' responses as coded by the SPs, using a communication checklist. RESULTS: There were no significant differences in student demographics between groups. The students who interacted with the empathy-feedback VP showed higher empathy in the SP interview than did the students in the backstory VP and the control VP groups [mean (SD) empathy scores coded on a 0-6 scale were 2.91 (0.16) vs. 2.20 (0.22) and 2.27 (0.21), respectively). The difference in scores was significant only for the empathy-feedback VP versus the backstory VP group (P = 0.027). The SPs rated the empathy-feedback and the backstory VP groups significantly higher than the control VP group on offering empathic statements (P < 0.0001), appearing warm and caring (P = 0.015), and forming rapport (P = 0.004). CONCLUSIONS: Feedback on empathy in a VP interaction increased students' empathy in encounters with SPs, as rated by trained assessors, whereas a simulation of patient shadowing did not. Both VP interventions increased students' empathy as rated by SPs, compared with the control VP group. PMID- 26841280 TI - Probiotics and prevention of eczema: have we enough data to draw conclusions? PMID- 26841279 TI - Decreased tryptophan and increased kynurenine levels in mastocytosis associated with digestive symptoms. AB - The main metabolism pathway of tryptophan is protein formation, but it can also be metabolized into serotonin and kynurenine. Indoleamine 2,3-dioxygenase (IDO) is the enzyme that catalyzes the degradation of tryptophan into kynurenine. Mastocytosis is a heterogeneous disease characterized by mast cell accumulation in various tissues with 57% of patients having gastrointestinal involvement. We studied tryptophan metabolism in mastocytosis patients displaying or not gastrointestinal features and healthy subjects (n = 26 in each group). Mastocytosis patients with digestive symptoms displayed significantly increased kynurenine level and IDO activity as compared to healthy controls and mastocytosis patients without digestive symptoms. This could be linked to mast cell-mediated digestive inflammation among patients with mastocytosis. This work is the first focusing on kynurenine pathway in a mast cell disease and could help to understand the pathogenesis of digestive features in mastocytosis as well as in other mast cell-mediated diseases. PMID- 26841281 TI - Breast MRI in Invasive Lobular Carcinoma: A Useful Investigation in Surgical Planning? AB - Magnetic resonance imaging (MRI) is highly sensitive in detecting invasive lobular carcinoma (ILC) of the breast. In our institution, patients who are deemed to be suitable for breast conserving surgery (BCS) with unifocal small ILC on standard imaging are offered breast MRI to exclude multifocal and larger ILC. Our study investigates the usefulness of breast MRI in ILC. A prospective cohort study over a 58-month period, including all consecutive patients with ILC having breast MRI. Primary objective was to find out the proportion of ILC patients where preoperative MRI caused a change in the surgical treatment. Secondary objectives included finding mastectomy rate (initial & final), re-operation rate, cancer size correlation with different imaging modalities and final histopathology, loco-regional recurrence and disease-free survival. A total of 334 bilateral breast MRI were performed including 72 (21.5%) MRI for ILC patients. All these MRI were carried out within 2 week of patients given the diagnosis (median 5.5 days). Age range was 24-83 (median 56.5) years. Nineteen of 72 ILC patients (26.4%) had a change in their planned operation from BCS to a different operation owing to MRI findings (seven patients with multifocal cancers, 10 with significantly larger size of the cancer and two with contralateral malignancy). Initial mastectomy rate was 31.9%, final mastectomy rate was 36.1% and re-operation rate in BCS group was 18.3%. MRI correlated better with ILC histopathology cancer size than mammogram and ultrasound scans. There was no statistically significant difference (p = 0.999) between the cancer size on histology (median 23 mm) and MRI (median 25 mm). However, mammogram (median 17 mm) and ultrasound (median 14.5 mm) scans showed cancer sizes significantly different to final histology cancer size (p = 0.0008 and p = 0.0021 respectively). Over a 44 months median follow-up (range 27-85), 95.8% disease free survival and 98.6% overall survival have been observed. One out of every four patients (26.4%) with ILC had a change in their planned operation due to MRI findings. A relatively high disease-free survival over a medium-term follow-up proves the oncological safety of MRI in ILC. Our study provides evidence in support of the targeted use of preoperative breast MRI among patients with ILC to improve surgical planning. PMID- 26841282 TI - Sequential Electron Transport and Vibrational Excitations in an Organic Molecule Coupled to Few-Layer Graphene Electrodes. AB - Graphene electrodes are promising candidates to improve reproducibility and stability in molecular electronics through new electrode-molecule anchoring strategies. Here we report sequential electron transport in few-layer graphene transistors containing individual curcuminoid-based molecules anchored to the electrodes via pi-pi orbital bonding. We show the coexistence of inelastic co tunneling excitations with single-electron transport physics due to an intermediate molecule-electrode coupling; we argue that an intermediate electron phonon coupling is the origin of these vibrational-assisted excitations. These experimental observations are complemented with density functional theory calculations to model electron transport and the interaction between electrons and vibrational modes of the curcuminoid molecule. We find that the calculated vibrational modes of the molecule are in agreement with the experimentally observed excitations. PMID- 26841284 TI - Progress in the theory of electrostatic interactions between charged particles. AB - In this perspective we examine recent theoretical developments in methods for calculating the electrostatic properties of charged particles of dielectric materials. Particular attention is paid to the phenomenon of like-charge attraction and we investigate the specific conditions under which particles carrying the same sign of charge can experience an attractive interaction. Given favourable circumstances, it is shown that even weakly polarisable materials, such as oil droplets and polymer particles, can experience like-charge attraction. Emphasis is also placed on the numerical accuracy of the multipole approach adopted in many electrostatic solutions and on the importance of establishing strict convergence criteria when addressing problems involving particulate materials with high dielectric constants. PMID- 26841283 TI - Circadian rhythm of calciotropic hormones, serum calcium, phosphorus and magnesium during the shortest and longest days of the year in horses in New Zealand. AB - A study was conducted to determine the circadian rhythms and trends of vitamin D metabolites including 25-hydroxyvitamin D3 , 25-hydroxyvitamin D2 , 1,25 dihydroxyvitamin D and parathyroid hormone, in addition to serum calcium, phosphorus and magnesium concentrations in horses over 48 h on the shortest and longest days of the year in 2013. Five healthy adult horses (Equus caballus) were on a constant pasture feeding regimen, and blood samples were collected from each horse every 3 h over a 48-h period, starting at 07:00 PM on day one and finishing at 07:00 PM on day three, for the measurement of calciotropic hormones and electrolytes. There was a significant difference between the serum concentration of calciotropic hormones, iCa, tCa, P and tMg between the shortest (winter) and longest (summer) days of the year in horses. Serum concentration of 25OHD3 was very low and mostly undetectable. Serum iCa, 1,25(OH)2 D and PTH concentrations clearly showed a circadian rhythm on the longest days of the year and serum tCa, P and tMg concentrations showed a diurnal pattern on the longest days (summer) of the year. None of the analytes showed any circadian rhythm on the shortest days (winter) of the year. The result of this study could have significant relevance to equine athletes travelling to international equestrian competitions and facing a huge time and seasonal differences that might affect their ability to adjust their circadian rhythms to new time zones. PMID- 26841285 TI - Radical Trachelectomy Performed During Pregnancy: A Review of the Literature. AB - OBJECTIVE: Cervical cancer is one of the most frequent malignant diseases diagnosed during pregnancy. Abdominal or vaginal radical trachelectomies are fertility-preserving alternatives to radical hysterectomy for young women with early-stage cervical cancer that can be performed during ongoing pregnancy. METHODS: A literature review of articles on this subject was conducted through a Medline search for articles published in English or French. RESULTS: At this moment, 21 cervical cancer patients, including ours (4 stage IA2, 16 IB1, and 1 IB2) who underwent radical trachelectomy during pregnancy have been reported. Of these, 10 were performed by vaginal route and 11 were abdominal radical trachelectomies. CONCLUSIONS: Radical trachelectomy could be offered as an option for pregnant patients with early invasive cervical cancer. It may help women avoid the triple losses of a desired pregnancy, fertility, and motherhood. PMID- 26841286 TI - Chromium alters lipopolysaccharide-induced inflammatory responses both in vivo and in vitro. AB - We demonstrated that pretreatment with chromium (Cr) significantly alters inflammatory responses of mice or macrophage cell lines. The mice were pretreated with 50 and 200 mg L(-1) of Cr dissolved in drinking water for 7 or 21 d, respectively. Then, the mice were challenged with lipopolysaccharide (LPS) or saline for 3 h. The body and liver weights significantly decreased after exposure to 200 mg L(-1) of Cr for both 7 and 21 d. Serious infiltration of inflammatory cells around the artery was found in the liver treated with 200 mg L(-1) of Cr for 7 and 21 d. The levels of tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL6) in peritoneal macrophage significantly increased after the treatment with 200 mg L(-1) of Cr for 7 d. Moreover, LPS-induced increases in the serum levels and the transcriptional status of some cytokine genes were amplified by the Cr pretreatment. In the in vitro test, the RAW264.7 cell line was pretreated with Cr for 3, 6, 12, and 24 h, followed by stimulation with LPS (1 MUg mL(-1)) for 6 h. LPS-induced the increases in TNFalpha, IL6, Interleukin 1alpha (IL1alpha), Interleukin-1beta (IL1beta), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX2) mRNA levels were significantly promoted by the pretreatment with Cr for 3, 6, and 12 h, whereas they were weakened by the pre-exposure to Cr for 24 h in a concentration-dependent manner. In addition, LPS induced the release of TNFalpha and IL6 in the medium was also significantly enhanced or suppressed by the different Cr pretreatment. The results suggested that Cr had the potential to induce immunotoxicity by altering the inflammatory responses. PMID- 26841287 TI - Phytoremediation of imazalil and tebuconazole by four emergent wetland plant species in hydroponic medium. AB - Pollution from pesticide residues in aquatic environments is of increasing concern. Imazalil and tebuconazole, two commonly used systemic pesticides, are water contaminants that can be removed by constructed wetlands. However, the phytoremediation capability of emergent wetland plants for imazalil and tebuconazole, especially the removal mechanisms involved, is poorly understood. This study compared the removal of both pesticides by four commonly used wetland plants, Typha latifolia, Phragmites australis, Iris pseudacorus and Juncus effusus, and aimed to understand the removal mechanisms involved. The plants were individually exposed to an initial concentration of 10 mg/L in hydroponic solution. At the end of the 24-day study period, the tebuconazole removal efficiencies were relatively lower (25%-41%) than those for imazalil (46%-96%) for all plant species studied. The removal of imazalil and tebuconazole fit a first-order kinetics model, with the exception of tebuconazole removal in solutions with I. pseudacorus. Changes in the enantiomeric fraction for imazalil and tebuconazole were detected in plant tissue but not in the hydroponic solutions; thus, the translocation and degradation processes were enantioselective in the plants. At the end of the study period, the accumulation of imazalil and tebuconazole in plant tissue was relatively low and constituted 2.8-14.4% of the total spiked pesticide in each vessel. Therefore, the studied plants were able to not only take up the pesticides but also metabolise them. PMID- 26841288 TI - Organophosphate flame retardants in household dust before and after introduction of new furniture. AB - Flame retardant compounds originating from household items collect in household dust, a reasonable proxy for human exposure. Contributions of specific items or behaviors to dust are difficult to separate. This study examined standardized college housing before and after the introduction of new, flame retardant couches in order to explore any effect that changing upholstered furniture may have on flame retardant concentrations in dust. Two contradictory hypotheses were posited: (1) that new furniture might increase flame retardant releases immediately after introduction due to initial off-gassing of new materials or (2) that older furniture would release more flame retardants due to mechanical breakdown of polyurethane foam. This study was designed to determine which of these processes dominated. Prior to the introduction of new furniture, TDCIPP was detected in 12/20 samples at a median concentration of 22 MUg/g and TCEP was detected in 1/20 samples at a concentration of 16 MUg/g. TDCIPP and TCEP were not detected in any samples (N = 29) after the introduction of new couches. TPHP was detected both before (in 11/20 samples) and after (in 5/29 samples) introduction of new couches; the median concentrations before and after were 63 +/- 49 and 16 +/- 11 MUg/g (standard deviation shown). Introduced couches contained TDCIPP (and not TPHP) at ~1.25% (w/w). These data support the second hypothesis and indicate that removal of older furniture decreases TDCIPP and TCEP concentrations in dust and may potentially reduce total flame retardant concentrations in dust, at least immediately after introduction of the new furniture. PMID- 26841289 TI - Use of solar advanced oxidation processes for wastewater treatment: Follow-up on degradation products, acute toxicity, genotoxicity and estrogenicity. AB - Wastewater tertiary treatment by advanced oxidation processes is thought to produce a treated effluent with lower toxicity than the initial influent. Here we performed tertiary treatment of a secondary effluent collected from a Waste Water Treatment Plant via homogeneous (solar/HSO5(-)/Fe(2+)) and heterogeneous (solar/TiO2) solar advanced oxidation aiming at the assessment of their effectiveness in terms of contaminants' and toxicity abatement in a plain solar reactor. A total of 53 organic contaminants were qualitatively identified by liquid chromatography coupled to high-resolution mass spectrometry after solid phase extraction. Solar advanced oxidation totally or partially removed the major part of contaminants detected within 4.5 h. Standard toxicity tests were performed using Vibrio fischeri, Daphnia magna, Pseudokirchneriella subcapitata and Brachionus calyciflorus organisms to evaluate acute and chronic toxicity in the secondary or tertiary effluents, and the EC50% was calculated. Estrogenic and genotoxic tests were carried out in an attempt to obtain an even sharper evaluation of potential hazardous effects due to micropollutants or their degradation by-products in wastewater. Genotoxic effects were not detected in effluent before or after treatment. However, we observed relevant estrogenic activity due to the high sensitivity of the HELN ERalpha cell line. PMID- 26841290 TI - Cytotoxic, genotoxic and mutagenic effects of sewage sludge on Allium cepa. AB - The objective of this study was to ascertain the cytotoxic, genotoxic and mutagenic potential of sewage sludge using Allium cepa bioassay. Solubilized and crude sludge from two sewage treatment stations (STSs), herein named JM and M, were tested. In addition, sanitized, crude and solubilized sludge were also analyzed from STS M. The treatments showed positive response to phytotoxicity, cytotoxicity, genotoxicity and/or mutagenicity. Despite negative results for MN F1 (micronuclei counted in F1 root cells, derived from meristematic cells), the monitoring of genotoxic and mutagenic activities of sewage sludge are recommended because in agricultural areas this residue is applied in large scale and continuously. Based on our results we advise caution in the use of sewage sludge in agricultural soils. PMID- 26841291 TI - Suppression of cadmium uptake in rice using fermented bark as a soil amendment. AB - The contamination of rice paddies with heavy metals has become a serious concern due to their high toxicity to human health. In this study, we developed a chemical-free, fermented bark amendment (FBA) and used it for organic rice cultivation. The application of FBA resulted in the fixation of heavy metals, especially cadmium (Cd), in the soil and suppressed their uptake in brown rice. The suppression of Cd uptake was most effective, since its uptake in rice from FBA-supplemented soil was 10 times lower than that from untreated soil under ordinary water-filling conditions. These results could be explained by the rapid conversion of sulfate ions to sulfide ions, which subsequently react with Cd producing insoluble sulfide species, as well as Cd adsorption to the decomposed bark in soil. The FBA did not affect the uptake of metals, such as calcium and iron, which are necessary for the growth of rice. Thus, the FBA may suppress Cd uptake in rice, and its effectiveness is related to application time and water regime. PMID- 26841292 TI - Photodegradation of polycyclic aromatic hydrocarbons in soils under a climate change base scenario. AB - The photodegradation of polycyclic aromatic hydrocarbons (PAHs) in two typical Mediterranean soils, either coarse- or fine-textured, was here investigated. Soil samples, spiked with the 16 US EPA priority PAHs, were incubated in a climate chamber at stable conditions of temperature (20 degrees C) and light (9.6 W m( 2)) for 28 days, simulating a climate change base scenario. PAH concentrations in soils were analyzed throughout the experiment, and correlated with data obtained by means of Microtox((r)) ecotoxicity test. Photodegradation was found to be dependent on exposure time, molecular weight of each hydrocarbon, and soil texture. Fine-textured soil was able to enhance sorption, being PAHs more photodegraded than in coarse-textured soil. According to the EC50 values reported by Microtox((r)), a higher detoxification was observed in fine-textured soil, being correlated with the outcomes of the analytical study. Significant photodegradation rates were detected for a number of PAHs, namely phenanthrene, anthracene, benzo(a)pyrene, and indeno(123-cd)pyrene. Benzo(a)pyrene, commonly used as an indicator for PAH pollution, was completely removed after 7 days of light exposure. In addition to the PAH chemical analysis and the ecotoxicity tests, a hydrogen isotope analysis of benzo(a)pyrene was also carried out. The degradation of this specific compound was associated to a high enrichment in (2)H, obtaining a maximum delta(2)H isotopic shift of +2320/00. This strong isotopic effect observed in benzo(a)pyrene suggests that compound-specific isotope analysis (CSIA) may be a powerful tool to monitor in situ degradation of PAHs. Moreover, hydrogen isotopes of benzo(a)pyrene evidenced a degradation process of unknown origin occurring in the darkness. PMID- 26841293 TI - Hexabromocyclododecanes (HBCDDs) in surface soils from coastal cities in North China: Correlation between diastereoisomer profiles and industrial activities. AB - Hexabromocyclododecane (HBCDD) is a brominated flame retardant with a wide range of industrial applications, although little is known about its patterns of spatial distribution in soils in relation to industrial emissions. This study has undertaken a large-scale investigation around an industrialized coastal area of China, exploring the concentrations, spatial distribution and diastereoisomer profiles of HBCDD in 188 surface soils from 21 coastal cities in North China. The detection frequency was 100% and concentrations of total HBCDD in the surface soils ranged from 0.123 to 363 ng g(-1) and averaged 7.20 ng g(-1), showing its ubiquitous existence at low levels. The spatial distribution of HBCDD exhibited a correlation with the location of known manufacturing facilities in Weifang, suggesting the production of HBCDD as major emission source. Diastereoisomer profiles varied in different cities. Diastereoisomer compositions in soils were compared with emissions from HBCDD industrial activities, and correlations were found between them, which has the potential for source identification. Although the contemporary concentrations of HBCDD in soils from the study were relatively low, HBCDD-containing products (expanded/extruded polystyrene insulation boards) would be a potential source after its service life, and attention needs to be paid to prioritizing large-scale waste management efforts. PMID- 26841294 TI - Monitoring ecotoxicity of disperse red 1 dye during photo-Fenton degradation. AB - The present work assessed the ecotoxicity of the commercially available form of the azo dye Disperse Red 1 (DR1) and the main degradation products generated during photo-Fenton degradation. The acute toxicity tests with the microcrustacean Daphnia similis showed that toxicity increased after 10 min of treatment, when 35% of the original concentration of the dye has been degraded but without decrease in total organic carbon concentration (TOC). The increase of toxicity was a consequence of generation of degradation products of higher toxicity than DR1, which achieved maximum concentration after 10 min reaction. The structures identified using LC/MS indicated that most of the intermediates were formed after addition of hydroxyl radical to benzenic ring but the cleavage of azo bond was also observed. The intermediates were further degraded and toxicity was then reduced to non toxic levels after 45 min experiment, when 98% of the initial concentration of DR1 was degraded and mineralization achieved 55%. The results of this study showed that the textile dye DR1 can be degraded by photo-Fenton process with removal of acute toxicity to D. similis even with incomplete mineralization. PMID- 26841295 TI - Twenty years of (non)reform in Victorian alcohol and other drug treatment policy. PMID- 26841296 TI - L-Carnitine for Treatment of Pegasparaginase-Induced Hepatotoxicity. AB - INTRODUCTION: Similar to pediatric regimens, multiple doses of L-asparaginase (PEG-Asp) are being increasingly used in adults with newly diagnosed acute lymphoblastic leukemia (ALL) with promising results. One of the most common side effects of the drug in adults is high-grade hyperbilirubinemia and transaminitis. Despite being almost always reversible and may not recur, clinicians may still be reluctant to continue with PEG-Asp in patients with liver toxicity, losing the benefit from multiple doses of the drug. CASE REPORT: We describe a case of adult ALL who developed PEG-Asp-related high grade liver toxicity. The rising hyperbilirubinemia and transaminitis rapidly and permanently reversed using the amino-acid derivative L-carnitine. This case goes in line with similar observations in animal models and humans. CONCLUSION: L-Carnitine may show therapeutic benefit in PEG-Asp-related hepatotoxicity and should be considered in clinical trials of the drug. PMID- 26841297 TI - An Unusual Cause of Abdominal Pain: Lupus Enteritis. PMID- 26841298 TI - Myasthenia of the Heart. PMID- 26841299 TI - Audible Coronary Artery Stenosis. AB - OBJECTIVE: Hemodynamically significant coronary artery stenoses generate turbulent blood flow patterns that manifest as intracoronary murmurs. This study aims to evaluate the performance of modern acoustic detection of these murmurs by acoustic signals captured from patients undergoing gold standard comparative coronary angiography. METHODS: We prospectively studied 156 patients undergoing elective coronary angiography, excluding those with acute coronary syndrome, prior chest surgery, or significant valvular disease. Acoustic signals were captured before arterial access. Angiographic degree of stenosis in each coronary artery was graded blinded to clinical and acoustic data. Acoustic data were analyzed blinded to clinical and angiographic data, categorizing subjects as "normal," "diseased," or "inconclusive." Of 156 patients examined, 123 generated analyzable data. RESULTS: Angiographically significant stenosis (>=50%) prevalence was 52% (18%, 23%, 11% with 1-, 2-, 3-vessel disease, respectively). Acoustic detection sensitivity and specificity for stenosis >=50% in any vessel were 0.70 and 0.80, respectively (negative predictive value, 0.71; positive predictive value, 0.79). Acoustic detection optimally identified stenosis >=50% with an area under the curve of 0.75. For stenosis >=50% in major vessels only (left main, proximal-mid left anterior descending, proximal-mid circumflex, proximal-mid right coronary), prevalence was 46%; sensitivity and specificity were 0.72 and 0.76, respectively (negative predictive value, 0.76; positive predictive value, 0.72; area under the curve, 0.76). CONCLUSIONS: Acoustic signal patterns and modern analysis techniques may be used to identify intracoronary murmurs generated by hemodynamically significant coronary artery stenoses in all major vessels. Further investigation is warranted to compare the clinical performance of this modality with current noninvasive approaches that evaluate patients at risk for atherosclerotic and obstructive coronary artery disease. PMID- 26841300 TI - Isolation, identification and antibiotic resistance of Campylobacter strains isolated from domestic and free-living pigeons. AB - 1. The aim of this study was to evaluate the occurrence of Campylobacter spp. in domestic and free-living pigeons and to evaluate the antibiotic resistance profiles. 2. The material consisted of cloacal swabs obtained from 108 homing pigeons and fresh faeces from 72 wild birds from Lublin and its vicinity. The identification of strains isolated on differential/selective media for Campylobacter spp. was carried out by MALDI-TOF and PCR. The susceptibility to antibiotics was evaluated by minimum inhibitory concentration (MIC) in Mueller Hinton broth. 3. A total of 35 strains of Campylobacter spp. were isolated; 27 were identified as Campylobacter jejuni and 8 as Campylobacter coli. Over half of the isolates were resistant to erythromycin and streptomycin, 40% of strains were resistant to tetracycline and ampicillin and 37% isolates were resistant to amoxicillin. Resistance to two or more antibiotics was observed in all strains tested. 4. The results indicate that both domestic and free-living pigeons are reservoirs for bacteria of the genus Campylobacter, which are characterised by varied and growing resistance to commonly used antibiotics. PMID- 26841302 TI - Electroconvulsive Therapy in Italy: Will Public Controversies Ever Stop? AB - BACKGROUND: The use of electroconvulsive therapy (ECT) is still very limited in Italy for ideological rather than scientific reasons. OBJECTIVES: To describe the public controversies surrounding ECT in Italy and to propose a plan of action to resolve the dispute. METHODS: We describe the historical background and the current public controversies about ECT by reviewing the official documents issued by the entities involved in the debate and by reporting our personal experiences of ECT practice. RESULTS: According to the highest legal and health authorities, there are no ethical reasons for doubting the licit nature of ECT. However, because of politically and ideologically based conflicts, public ECT centers are still lacking. The situation could further deteriorate because local initiatives are endeavoring to criminalize and ban the treatment. CONCLUSIONS: The enactment of specific regulations and guidelines concerning the use of ECT by the Italian government is highly warranted to increase the availability of the treatment. Education and information campaigns must strive to increase the knowledge of health professionals and the lay public regarding the safe and beneficial use of ECT. PMID- 26841301 TI - Gold(I)-Catalyzed Angle Strain Controlled Strategy to Furopyran Derivatives from Propargyl Vinyl Ethers: Insight into the Regioselectivity of Cycloisomerization. AB - A unique strategy for the regiospecific synthesis of bicyclic furopyran derivatives has been developed via a gold(I)-catalyzed propargyl-Claisen rearrangement/6-endo-trig cyclization of propargyl vinyl ethers. The introduction of angle strain into the substrates significantly altered the reaction's regioselectivity. Insight into the regioselectivity of the cycloisomerization was obtained with density functional theory calculations. PMID- 26841304 TI - Correction: Random Wiring, Ganglion Cell Mosaics, and the Functional Architecture of the Visual Cortex. PMID- 26841303 TI - Chemical composition, antioxidant, antitumor, anticancer and cytotoxic effects of Psidium guajava leaf extracts. AB - Context Psidium guajava L. (Myrtaceae) leaves are used in traditional medicines for the treatment of cancer, inflammation and other ailments. Objective The current study explores scientific validation for this traditional medication. Materials and methods We used ferric-reducing antioxidant power (FRAP) and 2,2 diphenyl-1-picryl hydrazil (DPPH) assays to estimate antioxidant activity of P. guajava leaf extracts (methanol, hexane and chloroform). Antitumour and in vivo cytotoxic activities were determined using potato disc assay (PDA) and brine shrimp lethality assay, respectively. Three human carcinoma cell lines (KBM5, SCC4 and U266) were incubated with different doses (10-100 MUg/mL) of extracts and the anticancer activity was estimated by MTT assay. NF-kappaB suppressing activity was determined using electrophoretic mobility shift assay (EMSA). Chemical composition of the three extracts was identified by GC-MS. Total phenolic and flavonoid contents were measured by colorimetric assays. Results and discussions The order of antioxidant activity of three extracts was methanol > chloroform > hexane. The IC50 values ranged from 22.73 to 51.65 MUg/mL for KBM5; 22.82 to 70.25 MUg/mL for SCC4 and 20.97 to 89.55 MUg/mL for U266 cells. The hexane extract exhibited potent antitumour (IC50 value = 65.02 MUg/mL) and cytotoxic (LC50 value = 32.18 MUg/mL) activities. This extract also completely inhibited the TNF-alpha induced NF-kappaB activation in KBM5 cells. GC-MS results showed that pyrogallol, palmitic acid and vitamin E were the major components of methanol, chloroform and hexane extracts. We observed significant (p < 0.05) difference in total phenolic and flavonoid contents of different solvent extracts. Conclusion The present study demonstrates that P. guajava leaf extracts play a substantial role against cancer and down-modulate inflammatory nuclear factor kB. PMID- 26841306 TI - Epigenetics and addiction. AB - Addictions are public health menaces. However, despite advances in addiction research, the cellular or molecular mechanisms that cause transition from recreational use to addiction remain to be elucidated. We have recently suggested that addiction may be secondary to long-term epigenetic modifications that determine the clinical course of substance use disorders. A better understanding of epigenetic mechanisms in animal models that mimic human conditions should help to usher in a new area of drug development against addiction. PMID- 26841305 TI - Paternal or Maternal Uniparental Disomy of Chromosome 16 Resulting in Homozygosity of a Mutant Allele Causes Fanconi Anemia. AB - Fanconi anemia (FA) is a rare inherited disorder caused by pathogenic variants in one of 19 FANC genes. FA patients display congenital abnormalities, and develop bone marrow failure, and cancer susceptibility. We identified homozygous mutations in four FA patients and, in each case, only one parent carried the obligate mutant allele. FANCA and FANCP/SLX4 genes, both located on chromosome 16, were the affected recessive FA genes in three and one family respectively. Genotyping with short tandem repeat markers and SNP arrays revealed uniparental disomy (UPD) of the entire mutation-carrying chromosome 16 in all four patients. One FANCA patient had paternal UPD, whereas FA in the other three patients resulted from maternal UPD. These are the first reported cases of UPD as a cause of FA. UPD indicates a reduced risk of having another child with FA in the family and has implications in prenatal diagnosis. PMID- 26841307 TI - Transcriptomic profiling of Alexandrium fundyense during physical interaction with or exposure to chemical signals from the parasite Amoebophrya. AB - Toxic microalgae have their own pathogens, and understanding the way in which these microalgae respond to antagonistic attacks may provide information about their capacity to persist during harmful algal bloom events. Here, we compared the effects of the physical presence of the parasite Amoebophrya sp. and exposure to waterborne cues from cultures infected with this parasite, on gene expression by the toxic dinoflagellates, Alexandrium fundyense. Compared with control samples, a total of 14,882 Alexandrium genes were differentially expressed over the whole-parasite infection cycle at three different time points (0, 6 and 96 h). RNA sequencing analyses indicated that exposure to the parasite and parasitic waterborne cues produced significant changes in the expression levels of Alexandrium genes associated with specific metabolic pathways. The observed upregulation of genes associated with glycolysis, the tricarboxylic acid cycle, fatty acid beta-oxidation, oxidative phosphorylation and photosynthesis suggests that parasite infection increases the energy demand of the host. The observed upregulation of genes correlated with signal transduction indicates that Alexandrium could be sensitized by parasite attacks. This response might prime the defence of the host, as indicated by the increased expression of several genes associated with defence and stress. Our findings provide a molecular overview of the response of a dinoflagellate to parasite infection. PMID- 26841308 TI - Peroxisome Proliferator-Activated Receptor Ligands and Their Role in Chronic Myeloid Leukemia: Therapeutic Strategies. AB - Imatinib therapy remains the gold standard for treatment of chronic myeloid leukemia; however, the acquired resistance to this therapeutic agent in patients has urged the scientists to devise modalities for overcoming this chemoresistance. For this purpose, initially therapeutic agents with higher tyrosine kinase activity were introduced, which had the potential for inhibiting even mutant forms of Bcr-Abl. Furthermore, coupling imatinib with peroxisome proliferator-activated receptor ligands also showed beneficial effects in chronic myeloid leukemia cell proliferation. These combination protocols inhibited cell growth and induced apoptosis as well as differentiation in chronic myeloid leukemia cell lines. In addition, peroxisome proliferator-activated receptors ligands increased imatinib uptake by upregulating the expression of human organic cation transporter 1. Taken together, peroxisome proliferator-activated receptors ligands are currently being considered as novel promising therapeutic candidates for chronic myeloid leukemia treatment, because they can synergistically enhance the efficacy of imatinib. In this article, we reviewed the potential of peroxisome proliferator-activated receptors ligands for use in chronic myeloid leukemia treatment. The mechanism of action of these therapeutics modalities are also presented in detail. PMID- 26841311 TI - Synthesis and structural characterization of monomeric mercury(II) selenolate complexes derived from 2-phenylbenzamide ligands. AB - Monomeric Hg(II) selenolate complexes derived from 2-phenylbenzamide ligands were prepared by oxidative addition of diselenides [{C6H4(CONR2)Se}2, R = Me, Et, iPr] to elemental Hg and reductive cleavage of the Se-N bond of isoselenazolone derivatives [(NO2)C6H3(CONSe)R, (R = allyl, nbutyl)] followed by the treatment with HgCl2. The complexes have been characterized by multinuclear NMR (1H, 13C and 77Se) spectroscopy and mass spectrometry which suggest the monomeric form of these in solution. The molecular structures of diselenides [C6H4(CONR2)Se]2 and mercury selenolates [Hg{(NO2)C6H3(CONH-C3H5) Se}2], [Hg{C6H4(CONiPr2)Se}2] and [Hg{C6H4(CONMe2)Se}2] were established by a single crystal X-ray diffraction study. Diselenides show strong intramolecular non-bonded Se?O interactions, which are influenced by the nature of C(O)NR2 and decrease with the sterically bulky alkyl substituent (Se?O =2.823 A for R = di-Me, 2.760 A for R = allyl, and 3.157 A for R = di-iPr). Mercury complexes derived from less bulky 2-phenyl-N,N dialkylbenzamide ligands associated with poor or no intramolecular nonbonded Hg?O interactions (4.91 A for R = di-Me, 4.199 A for R = allyl) and instead strong intermolecular Hg?O [2.792(3) and 2.820(4) A] for di-Me and allyl and Hg?Se [3.3212(5) and 3.4076(8) A] interactions were observed which lead to a dimeric form in the crystals. On the other hand, the mercury complex derived from the sterically bulky diisopropyl amide ligand shows a strong intramolecular non bonded Hg?O (2.860 A) interaction, adopts linear geometry and exists as a monomer. Thermogravimetric analysis (TGA) of the mercury selenolate complexes revealed two-step decomposition which leads to the formation of HgSe. The mercury selenolate complex 3c derived from the sterically bulky 2-phenyl N,Ndiisopropylbenzamide ligand decomposed to give HgSe in the range of 220-300 degrees C. PMID- 26841309 TI - Effect of interfacial composition and crumbliness on aroma release in soy protein/sugar beet pectin mixed emulsion gels. AB - BACKGROUND: In this study, soy protein isolate/sugar beet pectin (SPI/SBP) emulsion gels were prepared through an enzymatic gelation process. The effects of emulsifier (SBP, SPI or SPI/SBP complex) and emulsification process on the microstructure, texture, breakdown properties and aroma release behavior of resulting emulsion gels were investigated. RESULTS: Oil emulsification by SBP/SPI complex resulted in a higher amount of emulsifier absorbing on the oil-water interface than by SBP and SPI alone, indicating that a more compact interfacial network was formed. Flocculation of oil droplets was observed and corresponding emulsion gels exhibited lower fracture force and strain when the oil was emulsified by SPI and SBP/SPI complex. Moreover, emulsion gels with small droplets produced a greater quantity of small fragments after mastication. However, microstructure did not have a significant effect on breakdown properties of emulsion gels. Headspace gas chromatography analysis showed that the release rate of ethyl butyrate before and after mastication was significantly lower in emulsion gel with more compact network, but the release of aroma compounds with higher hydrophobicity did not show a significant influence of the microstructure and texture of emulsion gel. CONCLUSION: This finding provides a useful application for designing semi-solid foods with desirable flavor perception. (c) 2016 Society of Chemical Industry. PMID- 26841310 TI - Spectroscopic and Electrochemical Characterization of the Iron-Sulfur and Cobalamin Cofactors of TsrM, an Unusual Radical S-Adenosylmethionine Methylase. AB - TsrM, an annotated radical S-adenosylmethionine (SAM) enzyme, catalyzes the methylation of carbon 2 of the indole ring of L-tryptophan. Its reaction is the first step in the biosynthesis of the unique quinaldic acid moiety of thiostrepton A, a thiopeptide antibiotic. The appended methyl group derives from SAM; however, the enzyme also requires cobalamin and iron-sulfur cluster cofactors for turnover. In this work we report the overproduction and purification of TsrM and the characterization of its metallocofactors by UV visible, electron paramagnetic resonance, hyperfine sublevel correlation (HYSCORE), and Mossbauer spectroscopies as well as protein-film electrochemistry (PFE). The enzyme contains 1 equiv of its cobalamin cofactor in its as-isolated state and can be reconstituted with iron and sulfide to contain one [4Fe-4S] cluster with a site-differentiated Fe(2+)/Fe(3+) pair. Our spectroscopic studies suggest that TsrM binds cobalamin in an uncharacteristic five-coordinate base off/His-off conformation, whereby the dimethylbenzimidazole group is replaced by a non-nitrogenous ligand, which is likely a water molecule. Electrochemical analysis of the protein by PFE indicates a one-electron redox feature with a midpoint potential of -550 mV, which is assigned to a [4Fe-4S](2+)/[4Fe-4S](+) redox couple. Analysis of TsrM by Mossbauer and HYSCORE spectroscopies suggests that SAM does not bind to the unique iron site of the cluster in the same manner as in other radical SAM (RS) enzymes, yet its binding still perturbs the electronic configuration of both the Fe/S cluster and the cob(II)alamin cofactors. These biophysical studies suggest that TsrM is an atypical RS enzyme, consistent with its reported inability to catalyze formation of a 5' deoxyadenosyl 5'-radical. PMID- 26841312 TI - Risk Factors Associated with Left-Sided Cardiac Valve Calcification: A Case Control Study. AB - OBJECTIVES: To identify risk factors associated with cardiac valve calcification that is easily detectable through routine blood tests in patients who received valve replacement therapy. METHODS: Four hundred patients with valvular heart disease who underwent valve replacement surgery between December 2009 and January 2013 were enrolled in this study. Of these, 77 had valve calcification; the other 323 did not. Multivariate logistic regression analysis was used to assess for risk factors associated with valve calcification. RESULTS: In our study population, rheumatic valve lesions were the most common reason for valve replacement. Degenerative nonstenotic valve lesion was a protective factor and degenerative stenotic valve lesion was a strong risk factor for valve calcification. Serum levels of gamma-glutamyl transferase (GGT) of between 30 and 46 IU/l and >90 IU/l and total bilirubin (TBIL) of between 15 and 20 MUmol/l were positively correlated with valve calcification. Meanwhile, serum calcium (Ca2+) levels of between 2.3 and 2.4 mmol/l were negatively correlated with rheumatic valve calcification. CONCLUSIONS: Degenerative stenotic lesion is a risk factor and degenerative nonstenotic lesion a protective factor for cardiac valve calcification. Serum GGT and TBIL levels are positively correlated and serum Ca2+ levels negatively correlated with rheumatic cardiac valve calcification. PMID- 26841313 TI - Epidemiology of in-hospital mortality in acute patients admitted to a tertiary level hospital. AB - BACKGROUND: Healthcare professionals may have difficulty in recognising the dying patient in acute care settings, and yet, this is essential if timely end-of-life care is to be provided. While approximately one-third of patients who pass away in-hospital are reviewed by the rapid response team (RRT), there is limited available research on other factors associated with mortality within the hospital setting. AIMS: To describe the epidemiology of in-hospital mortality within a tertiary-level hospital, particularly in the context of RRT activation. METHODS: We utilised the database extraction of demographic, admission and RRT activation data on acute patients discharged from an Australian acute tertiary hospital between 1 January 2009 and 31 December 2013. Analyses included simple descriptors, Chi-squared and non-parametric Kruskal-Wallis tests as appropriate. RESULTS: Of the 44,297 patients discharged from our hospital, 1603 died during admission. The general medical, haematology/oncology and intensive care teams provided care for the majority of the patients who died. A small number of diagnoses had in-patient mortality rates of greater than 25%. These included respiratory failure, alcoholic liver disease, vascular disorders of the intestine, sepsis and aspiration pneumonia. Over 75% of patients who received a RRT call survived to hospital discharge; however, patients who received four or more RRT calls during admission had an in-hospital mortality rate of over 40%. CONCLUSION: Acute in-patient mortality is unequally distributed throughout the hospital, and a small number of diagnoses has large associated in-patient mortality rates. Repeated involvement of the RRT is associated with in-patient mortality. PMID- 26841314 TI - Characterization and correction of pressure drift in the ManoScan(TM) high resolution manometry system: In vitro and in vivo. AB - BACKGROUND: A substantial pressure drift in high-resolution manometry (HRM) has been reported; however, fundamental questions remain regarding the origin and management of this drift. The aim of this study was to provide critical in-depth analyses of ManoScan(TM) HRM drift in vitro and in vivo. METHODS: A total of sixteen 15-min studies and twelve 5-h studies were performed in a water bath at 37 degrees C at 4.0 cm depth (2.9 mmHg) with ESO and ESO Z catheters. Six 5-h in vitro studies were performed similarly at a depth of 9.0 cm (6.6 mmHg). Eight 15 min studies and nine 8-h in vivo studies were performed with healthy participants. Two correction methods - thermal compensation (TC) and interpolated thermal compensation (ITC) - were tested. KEY RESULTS: Overall pressure drift varied both between studies (p < 0.01) and within sensors (p < 0.01). Drift resulted from thermal shock, an initial pressure change at intubation, and baseline drift, a linear drift over time (R(2) > 0.96). Contrary to previous reports, there was no correlation between drift and average (r = -0.02) or maximum pressure exposure (r = -0.05). Following data correction, ITC had the lowest median error but persisted with a maximum error of 2.5 mmHg (IQR = 3.0). CONCLUSIONS & INFERENCES: The substantial drift in the ManoScan(TM) HRM system is highly variable and not corrected via the standard operating instructions. ITC has superior performance but requires communication with the manufacturer to enable this option. This has a substantial impact on clinical diagnosis, utility of existing normative data, and future research of HRM. PMID- 26841315 TI - Using multispectral imaging flow cytometry to assess an in vitro intracellular Burkholderia thailandensis infection model. AB - The use of in vitro models to understand the interaction of bacteria with host cells is well established. In vitro bacterial infection models are often used to quantify intracellular bacterial load by lysing cell populations and subsequently enumerating the bacteria. Modern established techniques employ the use of fluorescence technologies such as flow cytometry, fluorescent microscopy, and/or confocal microscopy. However, these techniques often lack either the quantification of large data sets (microscopy) or use of gross fluorescence signal which lacks the visual confirmation that can provide additional confidence in data sets. Multispectral imaging flow cytometry (MIFC) is a novel emerging field of technology. This technology captures a bright field and fluorescence image of cells in a flow using a charged coupled device camera. It allows the analysis of tens of thousands of single cell images, making it an extremely powerful technology. Here MIFC was used as an alternative method of analyzing intracellular bacterial infection using Burkholderia thailandensis E555 as a model organism. It has been demonstrated that the data produced using traditional enumeration is comparable to data analyzed using MIFC. It has also been shown that by using MIFC it is possible to generate other data on the dynamics of the infection model rather than viable counts alone. It has been demonstrated that it is possible to inhibit the uptake of bacteria into mammalian cells and identify differences between treated and untreated cell populations. The authors believe this to be the first use of MIFC to analyze a Burkholderia bacterial species during intracellular infection. (c) 2016 Crown copyright. Published by Wiley Periodicals Inc. on behalf of ISAC. PMID- 26841316 TI - Pediatric liver transplantation in Latin America: Where do we stand? AB - LT started in LA in 1968, and pediatric LT records are available starting in the 1990s. Currently, eight countries perform pediatric LT in LA. Registries by national organizations fail to report robust data on pediatric LT. The aim of this paper was to report on the pediatric LT activity in LA. Data were gathered retrospectively through information available in the national registries websites and from local centers. Of the eight countries that report pediatric LT activity, Brazil, Argentina, Mexico, and Colombia have adequate registries of the numbers of LT performed. These countries concentrate most of the activity for pediatric LT. A total of 4593 pediatric LT were reported in LA. Websites for national organizations do not provide open data on post-transplant survival rates or waiting list mortality. The information herein is based on reports by local centers. Overall, survival from select centers is similar to that reported on North American and European registries, between 80 and 90% in the first year post transplant. In conclusion, pediatric LT activity is growing in LA, especially in Brazil and Argentina. However, the lack of an appropriate LA registry restricts the assessment of quality and therefore restricts interventions aimed at quality improvements in different regions. PMID- 26841318 TI - Cross-cultural integration affects attitudes towards people with HIV/AIDS in Australia. AB - BACKGROUND: The stigma associated with HIV/AIDS represents a significant issue. It can hinder help-seeking behaviours, fracture relationships, conceal prevalence rates and curtail public health initiatives to reduce HIV/AIDS. Culture is known to shape this stigma - it influences how individuals and the communities they represent understand the causes of HIV/AIDS, how it can and should be treated, and how people living with HIV/AIDS (PLWHA) should be regarded. Following recent increases in both HIV/AIDS and cross-cultural migration, this study determines the effect of cross-cultural integration on the tendency to stigmatise PLWHA. METHODS: This was achieved by surveying adults who are at the nexus of two dissimilar cultures - adults from the Australian-Iranian community (n=236). While the Iranian culture is largely collectivistic, the Australian culture is largely individualistic. RESULTS: Survey results indicated the respondents represented a collectivistic (44.1%), transitional (33.5%) or an individualistic (22.4%) culture. Those within the collectivistic culture held the most stigmatising views about PLWHA, supporting coercive policies and reporting they would avoid PLWHA. Those within the individualistic culture held the most positive attitudes. Furthermore, regression analysis indicated that movement from a collectivistic to an individualistic culture significantly reduced stigmatising attitudes towards PLWHA. CONCLUSIONS: This study is the first to demonstrate the benefits afforded by an individualist culture, particularly for PLWHA. The article concludes with a discussion on the implications associated with these findings, particularly for researchers and practitioners within the health promotion field. PMID- 26841317 TI - Phosphoproteome analysis demonstrates the potential role of THRAP3 phosphorylation in androgen-independent prostate cancer cell growth. AB - Elucidating the androgen-independent growth mechanism is critical for developing effective treatment strategies to combat androgen-independent prostate cancer. We performed a comparative phosphoproteome analysis using a prostate cancer cell line, LNCaP, and an LNCaP-derived androgen-independent cell line, LNCaP-AI, to identify phosphoproteins involved in this mechanism. We performed quantitative comparisons of the phosphopeptide levels in tryptic digests of protein extracts from these cell lines using MS. We found that the levels of 69 phosphopeptides in 66 proteins significantly differed between LNCaP and LNCaP-AI. In particular, we focused on thyroid hormone receptor associated protein 3 (THRAP3), which is a known transcriptional coactivator of the androgen receptor. The phosphorylation level of THRAP3 was significantly lower at S248 and S253 in LNCaP-AI cells. Furthermore, pull-down assays showed that 32 proteins uniquely bound to the nonphosphorylatable mutant form of THRAP3, whereas 31 other proteins uniquely bound to the phosphorylation-mimic form. Many of the differentially interacting proteins were identified as being involved with RNA splicing and processing. These results suggest that the phosphorylation state of THRAP3 at S248 and S253 might be involved in the mechanism of androgen-independent prostate cancer cell growth by changing the interaction partners. PMID- 26841319 TI - Carbon Dioxide Versus Air Insufflation for Elective Colonoscopy: A Meta-Analysis and Systematic Review of Randomized Controlled Trials. AB - AIMS AND OBJECTIVE: The aim of this study was to conduct a meta-analysis and systematic review of randomized controlled trials (RCTs) comparing 2 methods of colonic insufflation for elective colonoscopy, that is, carbon dioxide (CO2) or air, and to evaluate their efficiency, safety, and side effects. MATERIALS AND METHODS: Prospective RCTs comparing CO2 versus air insufflation for colonic distension during colonoscopy were selected by searching PubMed, Medline, Embase, Science Citation Index, Current Contents, and the Cochrane Central Register of Controlled Trials published between January 1980 and October 2014. The outcome variables analyzed included procedural and immediate postprocedural pain (during, end, or within 15 min after procedure), early postprocedural pain (between 30 and 120 min), intermediate postprocedural pain (360 min) and late postprocedural pain (720 to 1140 min), cecal/ileal intubation rate, cecal/ileal intubation time, and total colonoscopy examination time. These outcomes were unanimously decided to be important as they influence the practical approach toward patient management within and outside of hospital. Random effects model was used to calculate the effect size of both binary and continuous data. Heterogeneity among the outcome variables of these trials was determined by the Cochran Q statistic and I2 index. The meta-analysis was prepared in accordance with PRISMA guidelines. RESULTS: Twenty-four RCTs totaling 3996 patients (CO2=2017, Air=1979) were analyzed. Statistically significant differences for the pooled effect size were observed for procedural and immediate postprocedural pain [weighted mean difference (WMD)=0.49; 95% confidence interval (CI), 0.32, 0.73; P=0.0005], early postprocedural pain between 30 and 120 minutes (WMD=0.25; 95% CI, 0.12, 0.49; P<0.0001), intermediate postprocedural pain, that is, 360 minutes after completion (WMD=0.35; 95% CI, 0.23, 0.52; P<0.0001), and late postprocedural pain between 720 and 1440 minutes (WMD=0.53; 95% CI, 0.34, 0.84; P=0.0061). Comparable effects were noted for cecal/ileal intubation rate (WMD=0.86; 95% CI, 0.61, 1.22; P=0.3975), cecal/ileal intubation time (WMD=-0.64; 95% CI, -1.38, 0.09; P=0.0860), and total examination time (WMD=-0.20; 95% CI, -0.96, 0.57; P=0.6133). CONCLUSIONS: On the basis of our meta-analysis and systematic review, we conclude that CO2 insufflation significantly reduces abdominal pain during and following the procedure lasting up to 24 hours. There is no difference in the cecal/ileal intubation rate and time and total examination time between the 2 methods. CO2 retention with CO2 insufflation during and after the colonoscopy shows inconsequential variation compared with air insufflation and has no adverse effect on patients. CO2 instead of air should be routinely utilized for colonoscopy. PMID- 26841320 TI - Impact of Preoperative Biliary Drainage on Surgical Outcomes in Periampullary and Hilar Malignancy: A Single-Center Experience. AB - The role of preoperative biliary drainage (PBD) for periampullary and hilar malignancy is still controversial. We retrospectively studied consecutive 144 patients (92 periampullary and 52 hilar malignancy) undergoing surgical resection to evaluate the effects of PBD on surgical outcomes. The rate of PBD was 59% and 56%, and postoperative complications developed in 27% and 19% in periampullary and hilar malignancy, respectively. Risk factors for postoperative complications were overweight [odds ratio (OR), 7.6] and depression (OR, 8.5) in distal malignancy and American society of anesthesiologists score of 3 (OR, 6.6), depression (OR, 13.8), and portal vein embolization (OR, 6.1) in hilar malignancy. PBD was not associated with postoperative complications but reinterventions for PBD were necessary in 43% and 27% in distal and hilar biliary obstruction. In conclusion, PBD in pancreatobiliary surgery was not associated with postoperative complications, but the improvement of PBD is necessary given the high rate of reinterventions. PMID- 26841321 TI - A Comparison of Laparoscopic Versus Open Left Hemihepatectomy for Hepatocellular Carcinoma. AB - BACKGROUND: With experience accumulation and technique innovation, laparoscopic left hemihepatectomy was performed in hepatocellular carcinoma patients. This study was designed to compare the perioperative outcomes of left hemihepatectomy through the laparoscopic and the open approaches. METHODS: From May 2012 to December 2014, we performed left hemihepatectomy in 45 hepatocellular carcinoma patients. Laparoscopic left hemihepatectomy (LLH) was performed in 20 patients and open left hemihepatectomy (OLH) was performed in 25 patients. All clinical data were analyzed retrospectively. RESULTS: The mean duration of operation was 143+/-35.6 minutes in the LLH and 137+/-29.8 minutes in the OLH group; no statistically significant difference was found between the 2 groups. The median blood loss in the LLH group was less than that in the OLH group (180+/-20.5 vs. 350+/-45.3 mL, P<0.05). The mean postoperative hospital stay was significantly lower in LLH compared with OLH (7+/-1 vs. 12+/-2.0 d; P<0.05). The postoperative morbidity rate was also significantly different between the groups; there was a tendency toward more severe complications in the OLH group compared with the LLH group. CONCLUSIONS: LLH can decrease complications, shorten the hospitalization time, is minimally invasive, and is a safe and effective technique. PMID- 26841322 TI - Soft Tissue Tumors in Adults: ESSR-Approved Guidelines for Diagnostic Imaging. PMID- 26841323 TI - Polyelectrolyte Complexes of Low Molecular Weight PEI and Citric Acid as Efficient and Nontoxic Vectors for in Vitro and in Vivo Gene Delivery. AB - Gene transfection mediated by the cationic polymer polyethylenimine (PEI) is considered a standard methodology. However, while highly branched PEIs form smaller polyplexes with DNA that exhibit high transfection efficiencies, they have significant cell toxicity. Conversely, low molecular weight PEIs (LMW-PEIs) with favorable cytotoxicity profiles display minimum transfection activities as a result of inadequate DNA complexation and protection. To solve this paradox, a novel polyelectrolyte complex was prepared by the ionic cross-linking of branched 1.8 kDa PEI with citric acid (CA). This system synergistically exploits the good cytotoxicity profile exhibited by LMW-PEI with the high transfection efficiencies shown by highly branched and high molecular weight PEIs. The polyectrolyte complex (1.8 kDa-PEI@CA) was obtained by a simple synthetic protocol based on the microwave irradiation of a solution of 1.8 kDa PEI and CA. Upon complexation with DNA, intrinsic properties of the resulting particles (size and surface charge) were measured and their ability to form stable polyplexes was determined. Compared with unmodified PEIs the new complexes behave as efficient gene vectors and showed enhanced DNA binding capability associated with facilitated intracellular DNA release and enhanced DNA protection from endonuclease degradation. In addition, while transfection values for LMW-PEIs are almost null, transfection efficiencies of the new reagent range from 2.5- to 3.8-fold to those of Lipofectamine 2000 and 25 kDa PEI in several cell lines in culture such as CHO k1, FTO2B hepatomas, L6 myoblasts, or NRK cells, simultaneously showing a negligible toxicity. Furthermore, the 1.8 kDa-PEI@CA polyelectrolyte complexes retained the capability to transfect eukaryotic cells in the presence of serum and exhibited the capability to promote in vivo transfection in mouse (as an animal model) with an enhanced efficiency compared to 25 kDa PEI. Results support the polyelectrolyte complex of LMW-PEI and CA as promising generic nonviral gene carriers. PMID- 26841326 TI - Heart valve disease: looking back and moving forward. PMID- 26841325 TI - Immediate hypersensitivity reactions to ibuprofen and other arylpropionic acid derivatives. AB - BACKGROUND: Although ibuprofen and other arylpropionic acid derivatives (APs) are the most common medicines involved in hypersensitivity drug reactions (HDRs) to NSAIDs, no patient series studies have been performed regarding immediate selective reactions (SRs) to these drugs. OBJECTIVE: To characterize patients with immediate selective HDRs to ibuprofen and other APs through clinical history and challenge. METHODS: Subjects who developed an HDR to APs less than 1 h after drug intake were included. Tolerance to aspirin was assessed and challenge was performed with ibuprofen in all cases, and additionally with the culprit drug (if different) in those patients that tolerated ibuprofen. Serum tryptase levels and tryptase immunohistochemical staining in skin biopsies were also assessed in some patients with a positive DPT to ibuprofen. RESULTS: From a total of 245 patients with a confirmed history of HDRs to APs, 17% were classified as selective immediate hypersensitivity reactors by both clinical history and challenge. A selective response to naproxen and dexketoprofen with tolerance to ibuprofen was found in 16 of 20 cases. Significant differences in serum tryptase levels were observed between 2 and 24 h in the 11 cases that were studied further. CONCLUSIONS: Within the group of patients with HDRs to NSAIDs, APs can induce immediate SRs. Within this group, selective responses to a single drug or responders to several APs may exist, suggesting potential immunological cross reactivity. PMID- 26841327 TI - Simulating Third-Order Nonlinear Optical Properties Using Damped Cubic Response Theory within Time-Dependent Density Functional Theory. AB - A general implementation for damped cubic response properties is presented using time-dependent density functional theory (TDDFT) and Slater-type orbital basis sets. To directly calculate two-photon absorption (TPA) cross sections, we also present an implementation of a reduced damped cubic response approach. Validation of the implementations includes a detailed comparison between response theory and the sum-over-states approach for calculating the nonlinear optical properties of LiH, as well as a comparison between the simulated and experimental TPA and third harmonic generation (THG) spectra for the dimethylamino-nitrostilbene (DANS) molecule. The study of LiH demonstrates the incorrect pole structure obtained in response theory due to the adiabatic approximation typically employed for the exchange-correlation kernel. For DANS, we find reasonable agreement between simulated and experimental TPA and THG spectra. Overall, this work shows that care must be taken when calculating higher-order response functions in the vicinity of one-photon poles due to the approximate kernels typically used in the simulations. PMID- 26841328 TI - Molecular Aberrance in Papillary Thyroid Microcarcinoma Bearing High Aggressiveness: Identifying a "Tibetan Mastiff Dog" From Puppies. AB - Today the most common differentiated thyroid cancer in many countries is papillary thyroid microcarcinoma (PTMC). Although the majority of PTMCs exhibit an indolent clinical course, a few possess high risk for aggressiveness with tumor invasion, metastasis, and even patient mortality. This imposes significant confusion and often dilemma in the clinical management of PTMC. The present review summarizes the molecular pathogenesis, particularly the major genetic alterations, of PTMC that may have prognostic values in assisting risk stratification of this cancer and identification of the most aggressive cases from the many well-behaving cases. J. Cell. Biochem. 117: 1491-1496, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26841330 TI - N-Heterocyclic Carbene Ligand-Enabled C(sp(3))-H Arylation of Piperidine and Tetrahydropyran Derivatives. AB - Pd(II)-catalyzed C(sp(3))-H arylation of saturated heterocycles with a wide range of aryl iodides is enabled by an N-heterocyclic carbene (NHC) ligand. A C(sp(3)) H insertion step by the Pd(II)/NHC complex in the absence of ArI is demonstrated experimentally for the first time. Experimental data suggests that the previously established NHC-mediated Pd(0)/Pd(II) catalytic manifold does not operate in this reaction. This transformation provides a new approach for diversifying pharmaceutically relevant piperidine and tetrahydropyran ring systems. PMID- 26841329 TI - Cerebellar ataxia in progressive supranuclear palsy: An autopsy study of PSP-C. AB - BACKGROUND: Cerebellar ataxia is an exclusion criterion for the clinical diagnosis of progressive supranuclear palsy, but a variant with predominant cerebellar ataxia has been reported. The aims of this study were to estimate the frequency of progressive supranuclear palsy with predominant cerebellar ataxia in an autopsy series from the United States and to compare clinical, pathologic, and genetic differences between progressive supranuclear palsy with and without predominant cerebellar ataxia. METHOD: We selected 100 consecutive patients with pathologically confirmed progressive supranuclear palsy who had been evaluated at the Mayo Clinic (referred to as the Mayo Clinic patient series) from our brain bank database (N = 1085). We next enriched in cases likely to have cerebellar ataxia by searching the remaining 985 cases for (1) an antemortem diagnosis of multiple system atrophy or (2) neuropathologic evidence of prominent degeneration of the cerebellum or cerebellar afferent nuclei. Subsequently, clinical, pathologic, and genetic features were compared between the two groups. RESULTS: One patient in the Mayo Clinic patient series (1%) met criteria for progressive supranuclear palsy with predominant cerebellar ataxia and had both cerebellar and mild midbrain atrophy on MRI. Four patients were identified with the targeted search. Four of the five patients were clinically misdiagnosed as multiple system atrophy. The severity of tau-related pathology and cerebellar degeneration were not different between the two groups. No differences were detected in tau genotypes. CONCLUSION: Although our data cannot provide definitive information about how to make an accurate clinical diagnosis, they should serve to raise awareness of progressive supranuclear palsy with predominant cerebellar ataxia in the differential diagnosis of multiple system atrophy. (c) 2016 Movement Disorder Society. PMID- 26841331 TI - Differences in Family Planning Services by Rural-urban Geography: Survey of Title X-Supported Clinics In Great Plains and Midwestern States. AB - CONTEXT: Understanding the nature of rural-urban variation in U.S. family planning services would help address disparities in unmet contraceptive need. METHODS: In 2012, some 558 Title X-supported clinics in 16 Great Plains and Midwestern states were surveyed. Rural-urban commuting area (RUCA) codes were used to categorize clinic locations as urban, large rural city, small rural town or isolated small rural town. Bivariate analyses examined key domains of service provision by RUCA category and clinic type. RESULTS: The proportion of clinics offering walk-in appointments was lower in isolated small rural towns (47%) than in the other RUCA categories (67-73%). Results were similar for sites that do not specialize in family planning or reproductive health, but no variation was seen among specialty clinics. Overall, availability of evening or weekend appointments varied in a linear fashion, falling from 73% in urban areas to 29% in isolated small rural towns. On-site provision of most hormonal methods was most common in urban areas and least common in isolated small rural towns, while provision of nonhormonal methods was similar across RUCA categories. Sixty percent of clinics provided IUDs or implants. For clinics that did not, the only barriers that varied geographically were low IUD demand and lack of trained IUD providers; these barriers were most common in isolated rural towns (42% and 70%, respectively). CONCLUSIONS: While important characteristics, such as clinics' specialization (or lack thereof), are linked to the provision of family planning services, geographic disparities exist. PMID- 26841332 TI - High-grade malignant transformation of a radiation-naive nasopharyngeal angiofibroma. AB - BACKGROUND: Nasopharyngeal angiofibromas are typically considered benign vascular neoplasms, with descriptions of high-grade sarcomatous change found only in lesions with prior radiotherapy. METHODS AND RESULTS: We describe the first reported case of high-grade malignant change in a nasopharyngeal angiofibroma naive to radiation. A 45-year-old man presented with left-sided nasal congestion and fullness and was found to have a left-sided nasopharyngeal mass with intracranial extension on CT scan. A biopsy of the mass revealed nasopharyngeal angiofibroma. The patient opted for MRI surveillance, which revealed interval growth 3 years later. Decompression surgery revealed only angiofibroma, but resection 9 months later demonstrated high-grade sarcoma and concomitant angiofibroma. The patient had residual disease which progressed through chemoradiation, and is now pursuing clinical trial enrollment. CONCLUSION: Malignant transformation of nasopharyngeal angiofibroma is extremely rare. As highlighted by this report, high-grade undifferentiated lesions may arise in tumors without previous radiation. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2425-E2427, 2016. PMID- 26841333 TI - Pharmacotherapy Treatment Patterns, Outcomes, and Health Resource Utilization Among Patients with Heart Failure with Reduced Ejection Fraction at a U.S. Academic Medical Center. AB - STUDY OBJECTIVE: To assess clinical characteristics, pharmacotherapy treatment patterns, resource utilization and associated charges, and morbidity and mortality outcomes among a real-world cohort of patients with heart failure with reduced ejection fraction (HFrEF) in an academic medical center setting. DESIGN: Retrospective analysis. DATA SOURCE: Electronic health record database that includes clinical, laboratory, and administrative data for all facilities of the University of Utah Health Care System. PATIENTS: A total of 989 adults with prevalent (preexisting) HFrEF, identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification code 428.x (heart failure) between January 1, 2007, and June 30, 2013, and who had a left ventricular ejection fraction of 40% or lower. MEASUREMENTS AND MAIN RESULTS: The cohort had a mean age of 64 +/- 15 years and was predominantly white (71%) and male (74%). Patients received beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), and aldosterone receptor antagonists (ARAs) at rates of 79%, 69%, and 29%, respectively. Patients achieved target doses of beta-blockers, ACEIs, and ARBs at rates of only 24%, 31%, and 13%, respectively. Overall, 58% of patients were prescribed dual therapy with a beta-blocker and an ACEI or ARB, and 19% were prescribed triple therapy (beta-blocker, an ACEI or ARB, and an ARA). Univariate and multivariate logistic regression models were used to assess the association between baseline characteristics with the presence of triple therapy. Two variables were statistically significant in both models: increasing age was associated with a lower odds of triple therapy (univariate: odds ratio [OR] 0.760, 95% confidence interval [CI] 0.673-0.857; multivariate: OR 0.768, 95% CI 0.625-0.942), whereas receipt of an implantable cardiac device was associated with a 2-fold increase in the odds of triple therapy (univariate: OR 2.1, 95% CI 1.4-3.1; multivariate: OR 2.1, 95% CI 1.3-3.5). During a mean +/- SD follow-up of 36 +/- 27 months, all cause mortality was 0.12 per person-year. There were 1311 all-cause hospitalizations of which 611 (47%) were for worsening heart failure. The rate of all-cause and heart failure-specific hospitalizations was 0.44 and 0.21 per person-year of follow-up, respectively. The median length of stay was 6.4 +/- 8.8 days, and the median charge was $22,310. The 30-day all-cause readmission rate was 20%, and the primary reason for readmission was heart failure in 65% of cases. CONCLUSION: This study demonstrates the continuing significant disease and economic burden for patients with HFrEF. Challenges remain in utilization of established disease-modifying therapy and in the treatment of patients with HFrEF and multiple comorbidities. PMID- 26841334 TI - Obesity-related endometrial cancer: an update on survivorship approaches to reducing cardiovascular death. AB - As the rate of obesity increases worldwide, so will the number of women diagnosed with obesity-related malignancy. The strongest correlation between obesity and cancer is endometrial cancer (EC). Obesity is the most significant modifiable risk factor for development of EC and also contributes to the most common cause of death in EC survivors-cardiovascular disease (CVD). Most cancer survivors after diagnosis do not implement lifestyle changes aimed at weight-loss and CVD risk reduction. This selective review highlights recent novel and unique approaches for managing CVD co-morbidities in EC survivorship. PMID- 26841335 TI - Effects of physical form of starter and forage provision to young calves on blood metabolites, liver composition and intestinal morphology. AB - This study evaluated the effects of physical form of starter feed and forage provision on the performance, blood metabolites, liver composition and intestinal morphology of dairy calves. Individually housed calves (n = 52; body weight = 41.5 +/- 2.5 kg) were randomly allocated (n = 13 per treatment) to one of the following four treatments: (i) ground starter feed (GS; mean particle size = 0.72 mm in diameter), (ii) textured starter feed (TS; mean particle size = 3.61 mm in diameter, including steam-flaked corn and barley), (iii) pelleted starter feed (PS; mean particle size = 4.53 mm in diameter) and (iv) ground starter feed with chopped alfalfa hay (GS + AH; mean particle size = 1.02 mm in diameter). The calves fed GS + AH diets had greater (p < 0.01) starter intake, final body weight and average daily gain compared with the other groups, while GS and TS groups both had greater (p < 0.01) starter intake than the PS group. Feed efficiency was found to be better (p < 0.05) in the TS group than in the GS or PS group, but not different from the GS + AH one. Compared with the other groups, the GS + AH group had the highest (p < 0.01), while the PS one had the lowest (p < 0.01) concentrations of blood glucose and triglyceride. The calves fed GS + AH had the highest blood concentrations of total protein, globulin, triiodothyronine (T3), thyroxin (T4), T3 : T4 ratio (p < 0.05) and levels of fat and glycogen in the liver (p < 0.01) compared with the other groups. The highest (p < 0.05) liver glycogen contents were observed in the GS + AH and TS groups. The duodenum, ileum and jejunum in the calves fed GS + AH exhibited a greater muscle layer thickness (p < 0.05) compared with the other groups. Based on the results obtained, the addition of dietary forage to starter diets positively influenced performance, liver composition and intestinal morphology in developing calves. PMID- 26841336 TI - Functional Choline Phosphate Polymers. AB - Zwitterionic polymers have been widely implemented in surface modification and as biomaterials that exhibit exceptional hydrophilicity, biocompatibility, and antifouling properties. However, a wider breadth of applications for polymer zwitterions is hindered by their inherent lack of functionality, requiring the integration of chain-end functionality or incorporation of functional comonomers along the polymer chain. Here we demonstrate the facile placement of unsaturated groups directly into zwitterionic methacrylate monomers, specifically choline phosphate structures, and show the utility of these monomers in controlled free radical polymerization. These versatile functional zwitterions are converted easily to polymer prodrugs, hydrogels, and other derivatives that establish the versatility of this novel materials platform. PMID- 26841337 TI - Prevalence of anaemia and iron deficiency in Portugal: the EMPIRE study. AB - BACKGROUND: Anaemia and iron deficiency are major public health problems with great implications on quality of life. AIMS: To establish the general prevalence of anaemia and iron deficiency in the adult Portuguese population and the prevalence by age, gender and region. METHODS: This was a population-based, cross sectional study (EMPIRE study) based on a representative sample of 7980 adults residing in mainland Portugal, which were selected using a random route sampling method. Levels of haemoglobin, ferritin, creatinine and C-reactive protein were measured by Point-of-Care assays; participants also completed a questionnaire about demography and medical history. RESULTS: The measured prevalence of anaemia was 19.9% (95% confidence interval: 19.0-20.8%); 84% of cases were previously undiagnosed. Anaemia was more prevalent among women (20.8%), young adults (18-34 years) (22.8-30.5%), older adults (21.0%), and pregnant women (54.2%). Anaemia varied across regions: from 15.5% in the Center region to 24.9% in the South. Iron deficiency was also highly prevalent: 16.7% (ferritin <15 ng/mL), 31.9% (<30 ng/mL), 53.3% (<50 ng/mL) and 84.3% (<100 ng/mL). Iron deficiency anaemia represented most anaemia cases: 29.0% (ferritin <15 ng/mL), 54.8% (<30 ng/mL), 75.4% (<50 ng/mL) and 92.5% (<100 ng/mL). CONCLUSION: Anaemia and iron deficiency are highly prevalent in Portugal and largely undiagnosed. Women, young adults and older individuals are more prone to present these conditions and there are marked regional asymmetries. Nationwide strategies for prevention, diagnosis and treatment of these conditions should be implemented. PMID- 26841339 TI - Insights into gas-phase reaction mechanisms of small carbon radicals using isomer resolved product detection. AB - For reactive gas-phase environments, including combustion, extraterrestrials atmospheres and our Earth's atmosphere, the availability of quality chemical data is essential for predictive chemical models. These data include reaction rate coefficients and product branching fractions. This perspective overviews recent isomer-resolved production detection experiments for reactions of two of the most reactive gas phase radicals, the CN and CH radicals, with a suite of small hydrocarbons. A particular focus is given to flow-tube experiments using synchrotron photoionization mass spectrometry. Coupled with computational studies and other experiment techniques, flow tube isomer-resolved product detection have provided significant mechanistic details of these radical + neutral reactions with some general patterns emerging. PMID- 26841338 TI - Lophirones B and C prevent aflatoxin B1-induced oxidative stress and DNA fragmentation in rat hepatocytes. AB - Context Despite the reported anticarcinogenic activity of lophirones B and C, no scientific information exists for its activity in rat hepatocytes. Objective Effect of lophirones B and C on aflatoxin B1 (AFB1)-induced oxidative stress, and DNA fragmentation in rat hepatocytes was investigated. Materials and methods Wistar rat hepatocytes were incubated with lophirones B and C (1 mg/mL) or sylimarin (1 mg/mL) in the presence or absence of AFB1. For an in vivo study, rats were orally administered with lophirones B and C, and/or AFB1 (20 MUg/d) for 9 weeks. Results Lophirones B and C lowered AFB1-mediated increase in nitric oxide, superoxide anion radicals, caspase-3 and fragmented DNA. Lophirones B and C attenuated AFB1-mediated decrease in superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and reduced glutathione. Also, lophirones B and C attenuated AFB1-mediated increase in conjugated dienes, lipid hydroperoxides and malondialdehyde in rat hepatocytes. Furthermore, AFB1-mediated alterations in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, albumin, total bilirubin and globulin in rat serum were significantly annulled in lophirones B and C-treated rats. Conclusion This study revealed that lophirones B and C prevented AFB1-induced oxidative damage in rat hepatocytes. PMID- 26841340 TI - Influence of temperature and fish thickness on the mass transfer kinetics during the cod (Gadus morhua) desalting process. AB - BACKGROUND: The aim of this study was to analyse the influence of desalting temperature, fish thickness and desalting time on the mass transfer kinetics during the cod desalting process by physico-chemical analyses. RESULTS: Both water uptake and salt loss increased with increasing temperature (15 degrees C > 10 degrees C > 5 degrees C) up to 24 h in 'thicker' pieces. The equilibrium achievement was faster in 'thinner' pieces and also with increasing temperature. Longer desalting times at 10 degrees C can be a good practice to be used during cod desalting at an industrial scale in order to obtain commercial products with higher yields. The faster mass transfer during desalting of 'thinner' pieces appears to follow three periods as a result of diffusion of the components (water, NaCl, and soluble proteins) because of the concentration differences, and pressure gradients due to expansion/shrinkage of the protein matrix, which is dependent on the NaCl content. The refractive index can be used by industry as an indirect measurement to determine the moment at which the 'thicker' samples are near the Z(NaCl) = Y(NaCl) equilibrium. CONCLUSION: Optimum combinations between the process variables analysed are essential in order to speed up the mass transfer kinetics during cod desalting at an industrial scale. (c) 2016 Society of Chemical Industry. PMID- 26841341 TI - Women's opinions on being weighed at routine antenatal visits. AB - OBJECTIVE: To assess the opinions of pregnant women regarding their weight gain and to assess the level of satisfaction and anxiety provoked by being weighed in clinic. DESIGN: Questionnaires were given to women participating in a randomised controlled trial comparing routine weighing in the antenatal clinic with standard care. SETTING: A tertiary hospital antenatal clinic in Melbourne, Australia. POPULATION: In all, 782 healthy pregnant women participated in the randomised controlled trial and 586 responded to the questionnaire. METHODS: A questionnaire was offered to all participants at 36 weeks of gestation gauging their satisfaction with their weight gain during pregnancy. The intervention group was asked about their level of satisfaction and anxiety provoked by being weighed in clinic. The control group was asked whether they would have liked to be weighed in clinic. Both groups were questioned about the influences on their weight gain. RESULTS: Women in both groups were satisfied with their weight gain during pregnancy. Seventy-three percent of women in the intervention group were very comfortable with being weighed in clinic. Approximately half of those in the control group would have favoured being weighed. Twenty-one percent of women said other people influenced their weight gain; mostly family members and two-thirds of them encouraged weight gain. Less than half of the women in the study used weighing scales at home. CONCLUSION: Women were satisfied with being weighed antenatally and it did not cause anxiety. Pregnant women accepted the re introduction of weighing in the antenatal clinic. PMID- 26841342 TI - Harnessing a Quantum Design Approach for Making Low-Loss Superlenses. AB - Recently, so-called "superlenses", made from metamaterials that are structured on a length scale much less than an optical wavelength, have shown impressive diffraction-beating image resolution, but they use materials with negative dielectric responses, and they absorb much of the light in a way that seriously degrades both the resolution and brightness of the image. Here we demonstrate an alternative "quantum metamaterials" (QM) approach that uses materials structured at the nanoscale, i.e., comparable to an electron wavelength. This allows us to use quantum mechanical design principles to generate structures with a highly elliptical isofrequency dispersion characteristic that circumvents this loss problem. The physics of the loss improvement is analyzed analytically and the QM superlens subdiffraction imaging is modeled numerically, with a finite-element method. Finally, we demonstrate a working QM superlens device, utilizing intersubband transitions between the confined electron states in a III-V semiconductor multiquantum-well. It images down to a resolution of better than ~ lambda/10 and has loss figures improved by roughly a decade over previous "classical" designs. This QM approach is an alternative paradigm for designing radiation-manipulating devices and offers the prospect of practical super resolving devices at new wavelengths and geometries. PMID- 26841343 TI - A statement synthesis of emotional eating and body size recognition: advancing nursing science related to obesity research. AB - AIM: A discussion of a statement synthesis of the relationship between the concepts of emotional eating and body size recognition. BACKGROUND: The interrelatedness of the concepts of emotional eating and body size recognition is poorly understood; however, both factors significantly impact weight management. Nurses can be instrumental in developing more effective weight management interventions as a critical step in helping to ameliorate the public health burden of obesity. DESIGN: This discussion article reports a literary statement synthesis. DATA SOURCES: Five quantitative research studies from 1996 - 2014 were identified, which examined the relationship between the concepts. IMPLICATIONS FOR NURSING: A relational statement delineating the direct association between the amount of self-reported emotional eating and an adult individual's recognition of their body size was constructed. Construction of a relational statement about emotional eating and recognition of body size is a step in the nursing theory-building process. CONCLUSION: The constructed relational statement will guide future research and nursing theory development and may ultimately help to construct more effective weight management interventions. PMID- 26841344 TI - Overexpression of miR-221 in peripheral blood lymphocytes in petrol station attendants: A population based cross-sectional study in southern China. AB - Benzene is a recognized environmental leukemogen, however, the mechanisms for its carcinogenesis have not been fully elucidated. Recently, miR-221, a suggested oncogene involved in a number of malignancies, has been detected with elevated expression levels in blood cells of patients with leukemia. To explore whether benzene exposure has an effect on the expression of miR-221, a population based cross-sectional study was conducted in southern China, with 97 petrol station attendants as the exposure group and 103 general residents as the control group. Plasma benzene was analyzed by using GC?MS. miR-221 in peripheral blood lymphocytes were measured by qRT-PCR and the DeltaCt value for each sample was calculated by normalizing the Ct value for miR-221 with U6 RNA (i.e., DeltaCt = CtmiR-221 - CtU6). Potential confounding factors were taken into account. Pearson correlation, univariate and multivariate logistic regression were performed in statistical analysis. The results showed that the air concentrations of benzene were significantly higher in petrol stations than in control sites (P < 0.05); The levels of benzene and miR-221 in exposure group were both significantly higher than in control group (P < 0.05) and there was a significant positive correlation between the two indexes (r = 0.851, P < 0.05); An association between benzene levels and the DeltaCt values for miR-221 was identified by univariate and multivariate logistic analysis (OR 0.274; 95%CI 0.117, 0.396). Our investigation indicates that benzene exposure may be related to elevated miR-221 expression in human lymphocytes. PMID- 26841345 TI - Measurement, "scriptural economies," and social justice: governing HIV/AIDS treatments by numbers in a fragile state, the Central African Republic (CAR). AB - Fragile states have been raising increasing concern among donors since the mid 2000s. The policies of the Global Fund to fight HIV/AIDS, Malaria, and Tuberculosis (GF) have not excluded fragile states, and this source has provided financing for these countries according to standardized procedures. They represent interesting cases for exploring the meaning and role of measurement in a globalized context. Measurement in the field of HIV/AIDS and its treatment has given rise to a private outsourcing of expertise and auditing, thereby creating a new form of value based on the social process of registration and the creation of realities produced by the intervention itself. These "scriptural economies" must be questioned in terms of the production of knowledge, but also in terms of social justice. Governing HIV/AIDS treatments by numbers in a fragile state is explored in this article through the experience of the Central African Republic (CAR) in terms of epidemiology and access to antiretroviral drugs. The unexpected effects of performance-based programs in this context underline the need for global health governance to be re-embedded into a social justice framework. PMID- 26841347 TI - Can neonatal MRI predict long-term motor outcome following preterm birth? PMID- 26841346 TI - Sufficiency of Single-Arm Studies to Support Registration of Targeted Agents in Molecularly Selected Patients with Cancer: Lessons from the Clinical Development of Crizotinib. PMID- 26841349 TI - Can Intraoperative Neurological Preconditioning Occur After Intraoperative Hypotensive Episodes? PMID- 26841348 TI - Tissue microarray use for immunohistochemical study of ameloblastoma. AB - BACKGROUND: Ameloblastoma is a locally aggressive odontogenic tumor with high rates of recurrence. To better understand the molecular basis of ameloblastoma, tissue microarray (TMA) may represent a useful tool. However, despite TMA has been considered a high-throughput technique for different human neoplasms, it remains to be validated in the ameloblastoma context. Therefore, the objective of this study was to validate TMA for immunohistochemical study of ameloblastoma, determining its most appropriate design. METHODS: Forty cases of ameloblastoma were manually distributed in two TMA blocks assembled in triplicate containing 1.0- and 2.0-mm cores (20 cases each). Immunohistochemistry for cytokeratins 14 and 19, and Bcl-2 and Ki-67 was performed, and semiquantitative analysis was performed. Results obtained with TMA sections were compared to their corresponding conventional whole-section slides (CWSS). RESULTS: Kappa statistical test demonstrated that both 1.0- and 2.0-mm cores assessed as duplicate or triplicate significantly correlated with CWSS, with higher levels obtained using Ki67 (k = 0.98, 0.97, 0.88, 0.87) and CK19 (k = 0.62, 0.58, 0.85, 0.85). There was no significant difference between 1.0- and 2.0-mm cores, and between duplicate and triplicate values. 1.0-mm TMA showed a higher index of core loss (33.74% vs. 4.99%). CONCLUSION: Using a manual arrayer, it was demonstrated that 1.0-mm TMA arranged in duplicate is a valid method for ameloblastoma immunohistochemical study with satisfactory levels of agreement between TMA cylinders and CWSS. PMID- 26841351 TI - Perioperative Management of Children With Giant Encephalocele: A Clinical Report of 29 Cases. AB - BACKGROUND: Giant encephalocele, a rare entity, makes anesthesiologists wary of challenging anesthetic course. Apart from inherent challenges of pediatric anesthesia, the anesthesiologist has to deal with unusual positioning, difficult tracheal intubation, and associated anomalies during the perioperative course. MATERIALS AND METHODS: Medical records of 29 children with giant encephalocele, who underwent excision and repair, during a period of 13 years, were retrospectively analyzed. Data pertaining to anesthetic management, perioperative complications, and outcome at discharge were reviewed. RESULTS: The average age at admission was 164 days. Hydrocephalus and delayed milestones were present in 19 (65.5%) and 7 (24.1%) children, respectively. Difficulty in tracheal intubation was encountered, in 15 (51.7%) children. Tracheal intubation was attempted with direct laryngoscopy, most often, in lateral position (24 [82.8%]). Intraoperative hemodynamic and respiratory complications were observed in 9 (31.0%) and 5 (17.2%) children, respectively. Intraoperative hypothermia was observed in 4 (13.8%) children. The average stay in the intensive care unit was 2.7 days and average hospital stay was 11.5 days. The condition at discharge remained same as the preoperative period in 24 children (82.7%), deteriorated in 2 (6.9%), and 3 children (10.3%) died. CONCLUSIONS: Management of children with giant encephalocele requires the updated knowledge on possible difficulties encountered during the perioperative period. They need specialized anesthetic care for dealing with difficult tracheal intubation, associated congenital anomalies, unusual positioning, electrolyte abnormalities, hypothermia, and cardiorespiratory disturbances. For securing the airway, we suggest the practice of direct laryngoscopy in lateral position after inhalational induction. Muscle relaxant should be administered only after visualization of the glottis. PMID- 26841352 TI - Perioperative Evaluation and Care of Patients With Mild to Moderate Cerebrovascular Disease: It's Time to Develop Treatment Guidelines! PMID- 26841355 TI - Proliferation by many other names: Monitoring cell cycle progression and cell division by flow cytometry. PMID- 26841354 TI - Predictors of awareness of standard drink labelling and drinking guidelines to reduce negative health effects among Australian drinkers. AB - INTRODUCTION AND AIMS: This study examined rates of awareness of standard drink labelling and drinking guidelines among Australian adult drinkers. Demographic predictors of these two outcomes were also explored. DESIGN AND METHODS: Online survey panel participants aged 18-45 years(n = 1061; mean age = 33.2 years) completed an online survey assessing demographics, alcohol consumption patterns, awareness of standard drink labels and the National Health and Medical Research Council (NHMRC) guidelines, and support for more detailed labels. RESULTS: The majority (80%) of participants had seen standard drink labels on alcohol products; with younger drinkers, those from a regional/rural location and high risk drinkers significantly more likely to have seen such labelling. Most respondents estimated at or below the maximum number of drinks stipulated in the NHMRC guidelines. However, their estimates of the levels for male drinkers were significantly higher than for female drinkers. High-risk drinkers were significantly less likely to provide accurate estimates, while those who had seen the standard drink logo were significantly more likely to provide accurate estimates of drinking levels to reduce the risk of long-term harms only. Just under three-quarters of respondents supported the inclusion of more information on labels regarding guidelines to reduce negative health effects. DISCUSSION AND CONCLUSIONS: The current standard drink labelling approach fails to address high risk drinkers. The inclusion of information about NHMRC guidelines on alcohol labels, and placing standard drink labelling on the front of products could improve awareness of what constitutes a standard drink and safe levels of consumption among Australian drinkers.[Kerri Coomber, Sandra C. Jones, Florentine Martino, Peter G. Miller. Predictors of awareness of standard drink labelling and drinking guidelines to reduce negative health effects among Australian drinkers. Drug Alcohol Rev 2017;36:200-209]. PMID- 26841353 TI - Activation-Induced Killer Cell Immunoglobulin-like Receptor 3DL2 Binding to HLA B27 Licenses Pathogenic T Cell Differentiation in Spondyloarthritis. AB - OBJECTIVE: In the spondyloarthritides (SpA), increased numbers of CD4+ T cells express killer cell immunoglobulin-like receptor 3DL2 (KIR-3DL2). The aim of this study was to determine the factors that induce KIR-3DL2 expression, and to characterize the relationship between HLA-B27 and the phenotype and function of KIR-3DL2-expressing CD4+ T cells in SpA. METHODS: In total, 34 B27+ patients with SpA, 28 age- and sex-matched healthy controls (20 B27- and 8 B27+), and 9 patients with rheumatoid arthritis were studied. KIR-3DL2 expression and other phenotypic characteristics of peripheral blood and synovial fluid CD4+ T cells were studied by flow cytometry, quantitative polymerase chain reaction, and Western blotting. T cell receptor clonality was determined by template-switch anchored reverse transcription-polymerase chain reaction and sequencing analysis. Cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: Cellular activation induced KIR-3DL2 expression on both naive and effector CD4+ T cells. KIR-3DL2 binding to B27+ cells promoted expression of KIR-3DL2, the Th17-specific transcription factor retinoic acid receptor-related orphan nuclear receptor gammat, and the antiapoptotic factor B cell lymphoma 2. KIR-3DL2+CD4+ T cells in patients with ankylosing spondylitis were oligoclonal and enriched for markers of T cell activation and for the gut homing receptor CCR9. In the presence of B27+ antigen-presenting cells, KIR-3DL2+CD4+ T cells produced less interleukin-2 (IL 2) but more IL-17. This effect was blocked by HC10, an antibody that inhibits the binding of KIR-3DL2 to B27 heavy chains. CONCLUSION: KIR-3DL2 binding to HLA-B27 licenses Th17 cell differentiation in SpA. These findings raise the therapeutic potential of targeting HLA-B27-KIR-3DL2 interactions for the treatment of B27+ patients with SpA. PMID- 26841356 TI - Dinuclear ruthenium(ii) complexes containing one inert metal centre and one coordinatively-labile metal centre: syntheses and biological activities. AB - A series of non-symmetric dinuclear polypyridylruthenium(ii) complexes (Rubbn-Cl) that contain one inert metal centre and one coordinatively-labile metal centre, linked by the bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane ligand ("bbn" for n = 7, 12 and 16), have been synthesised and their potential as antimicrobial agents examined. The minimum inhibitory concentrations (MIC) of the ruthenium(II) complexes were determined against four strains of bacteria--Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), and Gram-negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). The Rubbn-Cl complexes displayed good antimicrobial activity, with Rubb12-Cl being the most active complex against both Gram-positive and Gram negative strains. Interestingly, Rubb7-Cl was found to be eight- and sixteen-fold more active towards E. coli than against S. aureus and MRSA, respectively. The cytotoxicities of the Rubbn-Cl complexes against three eukaryotic cell lines--two kidney cell lines (BHK and HEK-293) and one liver cell line (HepG2)--were examined. The Rubbn-Cl complexes were found to be considerably less toxic towards eukaryotic cells than S. aureus, MRSA and E. coli, with Rubb12-Cl being thirty- to eighty-times more toxic to the bacteria than to BHK, HEK-293 or HepG2 cells. Unexpectedly, Rubb7-Cl was far more toxic to HepG2 cells (24 h-IC50 = 3.7 MUM) and far less toxic to BHK cells (24 h-IC50 = 238 MUM) than the Rubb12-Cl and Rubb16-Cl complexes. In order to understand the unexpected large differences in the cytotoxicities of the Rubbn-Cl complexes towards eukaryotic cells, a confocal microscopic study of their intracellular localisation was undertaken. The results suggest that the observed cytotoxicity might be related to the extent of DNA binding. PMID- 26841358 TI - (16) O/(18) O Exchange of Aldehydes and Ketones caused by H2 (18) O in the Mechanistic Investigation of Organocatalyzed Michael, Mannich, and Aldol Reactions. AB - Organocatalyzed Michael, Mannich, and aldol reactions of aldehydes or ketones, as nucleophiles, have triggered several discussions regarding their reaction mechanism. H2 (18) O has been utilized to determine if the reaction proceeds through an enamine or enol mechanism by monitoring the ratio of (18) O incorporated into the final product. In this communication, we describe the risk of H2 (18) O as an evaluation tool for this mechanistic investigation. We have demonstrated that exchange of (16) O/(18) O occurs in the aldehyde or ketone starting material, caused by the presence of H2 (18) O and amine catalysts, before the Michael, Mannich, and aldol reactions proceed. Because the newly generated (18) O starting aldehydes or ketones and (16) O water affect the incorporation ratio of (18) O in the final product, the use of H2 (18) O would not be appropriate to distinguish the mechanism of these organocatalyzed reactions. PMID- 26841357 TI - mutation3D: Cancer Gene Prediction Through Atomic Clustering of Coding Variants in the Structural Proteome. AB - A new algorithm and Web server, mutation3D (http://mutation3d.org), proposes driver genes in cancer by identifying clusters of amino acid substitutions within tertiary protein structures. We demonstrate the feasibility of using a 3D clustering approach to implicate proteins in cancer based on explorations of single proteins using the mutation3D Web interface. On a large scale, we show that clustering with mutation3D is able to separate functional from nonfunctional mutations by analyzing a combination of 8,869 known inherited disease mutations and 2,004 SNPs overlaid together upon the same sets of crystal structures and homology models. Further, we present a systematic analysis of whole-genome and whole-exome cancer datasets to demonstrate that mutation3D identifies many known cancer genes as well as previously underexplored target genes. The mutation3D Web interface allows users to analyze their own mutation data in a variety of popular formats and provides seamless access to explore mutation clusters derived from over 975,000 somatic mutations reported by 6,811 cancer sequencing studies. The mutation3D Web interface is freely available with all major browsers supported. PMID- 26841359 TI - Do Smoking Bans Improve Neonatal Health? AB - RESEARCH OBJECTIVE: To estimate the effects of smoking bans on neonatal health outcomes and maternal smoking behavior during pregnancy. DATA SOURCES: Restricted use 1991-2009 Natality Detail Files, a Clean Air Dates Table Report, and the Tax Burden of Tobacco. STUDY DESIGN: A quasi-experimental study using difference-in differences estimation based on legislative history of smoking restrictions or bans by type/place/county/state level. Dependent variables included average monthly percentage of healthy neonates, of term neonates born with low and very low birth weight, of premature births, of maternal smokers, and average number of cigarettes smoked daily during pregnancy. The analyses were restricted to singleton births and those that occurred in the same county as mother's county of residence. DATA COLLECTION/EXTRACTION METHODS: The data from three data sources were combined using Federal Information Processing Standard codes. PRINCIPAL FINDINGS: Results of the overall and stratified by maternal smoking status, educational level, and age regression analyses suggested no appreciable effect of smoking bans on neonatal health. Smoking bans had also no effect on maternal smoking behavior. CONCLUSION: While there are health benefits to the general population from smoking bans, their effects on neonatal health outcomes and maternal smoking during pregnancy seem to be limited. PMID- 26841360 TI - "I Hope I Get Movie-star Teeth": Doing the Exceptional Normal in Orthodontic Practice for Young People. AB - Orthodontics offer young people the chance to improve their bite and adjust their appearances. The most common reasons for orthodontic treatment concern general dentists', parents' or children's dissatisfaction with the esthetics of the bite. My aim is to analyze how esthetic norms are used during three activities preceding possible treatment with fixed appliances. The evaluation indexes signal definitiveness and are the essential grounds for decision-making. In parallel, practitioners and patients refer to self-perceived satisfaction with appearances. Visualizations of divergences and the improved future bite become part of an interactive process that upholds what I conceptualize as "the exceptional normal." Insights into this process contribute to a better understanding of how medical practices intended to measure and safeguard children's and young people's health at the same time mobilize patients to look and feel better. The article is based on an ethnographic study at two orthodontic clinics. PMID- 26841361 TI - Divorce: Using Psychologists' Skills for Transformation and Conflict Reduction. AB - The litigious divorce process often leaves children with parents who are at "war" and have little ability to coparent effectively. This article discusses some of the Alternative Dispute Resolution (ADR) processes designed to lessen conflict both before and after divorce. It also addresses the important work of psychologists serving in the roles of child therapists and reunification clinicians doing the difficult work of helping to heal fractured child-parent relationships. Ethical challenges are addressed and future directions for applied research are suggested. PMID- 26841362 TI - Vascularized composite allotransplantation: a closer look at the banff working classification. AB - The first Banff vascularized composite allotransplantation meeting was held in 2007 to standardize criteria for the characterization and reporting of severity and types of rejection. As a result, the 2007 Banff VCA working classification for skin allograft pathology was formalized and now serves as the standard for diagnosis of VCA rejection. Similar to other working classification systems, strengths and limitations have been identified including the adequacy of the specimen, the definition of severity between grades, the reproducibility, the adequacy of the specimens, the types of rejection, and the integration of newer technologies such as molecular and genomic approaches. Although a relatively few number of cases have been performed and followed up to date, additional phenotypes such as antibody-mediated rejection, fibrosis, atrophy, and vascular changes are being reported and characterized based on accumulated experience in the field of VCA and parallels with other solid organs. This study aims to consider strengths and limitations of the Banff VCA working system and highlights ongoing challenges and opportunities available related to histopathology in this emerging field of transplantation. PMID- 26841363 TI - pH-Triggered Charge-Reversal Polyurethane Micelles for Controlled Release of Doxorubicin. AB - A series of pH-triggered charge-reversal polyurethane copolymers (PS-PUs) containing methoxyl-poly(ethylene glycol) (mPEG), carboxylic acid groups, and piperazine groups is presented in this work. The obtained PS-PUs copolymers can form into stable micelles at pH 7.4, which response to a narrow pH change (5.5 7.5) and show a tunable pH-triggered charge-reversal property. Doxorubicin (DOX) is encapsulated into the PS-PU micelles as a model drug. The drug release of DOX loaded PS-PU micelles shows an obviously stepped-up with reducing the pH. Meanwhile, it is found that the charge-reversal property can improve the cellular uptake behavior and intracellular drug release in both HeLa cells and MCF-7 cells. Additionally, the time-dependent cytotoxicity of the DOX-loaded PS-PU micelles is confirmed by MTT assay. Attributed to the tunable charge-reversal property through changing the molar ratio of piperazine/carboxyl, the PS-PU micelles will be a potential candidate as an intelligent drug delivery system in future studies. PMID- 26841364 TI - Pregnancy after weight loss surgery: a commentary. PMID- 26841365 TI - Improved control of childhood asthma with low-dose, short-term vitamin D supplementation: a randomized, double-blind, placebo-controlled trial. AB - BACKGROUND: In our prior randomized trial on preventing influenza, asthma attacks as a secondary outcome occurred less often in the vitamin D group than in the placebo group. We aimed to clarify whether low-dose, short-term vitamin D supplementation, in addition to standard treatments, improves control of childhood asthma. METHODS: We conducted a randomized, double-blind, placebo controlled trial comparing vitamin D3 supplements (800 IU/day) with placebo for 2 months in schoolchildren with asthma. The primary outcomes were frequency and severity of asthma judging from changes in asthma control levels defined by the Global Initiative for Asthma (GINA) by collaborating doctors at 2 and 6 months. RESULTS: Japanese schoolchildren with asthma (n = 89) were randomly assigned to receive vitamin D (n = 54) or placebo (n = 35). At 2 months, GINA asthma control was significantly more improved in the vitamin D group compared with the placebo group (P = 0.015). Childhood asthma control test (CACT) scores, a secondary outcome, were also significantly (P = 0.004) improved in the vitamin D group compared with the placebo group at 2 months, and differences remained significant (P = 0.012) at 6 months. The proportion of patients with a peak expiratory flow rate <80% predicted was significantly less in the vitamin D group (8/54: 15%) than in the placebo group (12/35: 34%) at 6 months (P = 0.032). CONCLUSIONS: Low dose, short-term vitamin D supplementation in addition to standard treatment may improve levels of asthma control in schoolchildren. PMID- 26841366 TI - Barley root hair growth and morphology in soil, sand, and water solution media and relationship with nickel toxicity. AB - Barley, Hordeum vulgare (Doyce), was grown in the 3 media of soil, hydroponic sand solution (sand), and hydroponic water solution (water) culture at the same environmental conditions for 4 d. Barley roots were scanned, and root morphology was analyzed. Plants grown in the 3 media had different root morphology and nickel (Ni) toxicity response. Root elongations and total root lengths followed the sequence soil > sand > water. Plants grown in water culture were more sensitive to Ni toxicity and had greater root hair length than those from soil and sand cultures, which increased root surface area. The unit root surface area as root surface area per centimeter of length of root followed the sequence water > sand > soil and was found to be related with root elongation. Including the unit root surface area, the difference in root elongation and 50% effective concentration were diminished, and percentage of root elongations can be improved with a root mean square error approximately 10% for plants grown in different media. Because the unit root surface area of plants in sand culture is closer to that in soil culture, the sand culture method, not water culture, is recommended for toxicity parameter estimation. Environ Toxicol Chem 2016;35:2125-2133. (c) 2016 SETAC. PMID- 26841367 TI - Testing moderation in network meta-analysis with individual participant data. AB - Meta-analytic methods for combining data from multiple intervention trials are commonly used to estimate the effectiveness of an intervention. They can also be extended to study comparative effectiveness, testing which of several alternative interventions is expected to have the strongest effect. This often requires network meta-analysis (NMA), which combines trials involving direct comparison of two interventions within the same trial and indirect comparisons across trials. In this paper, we extend existing network methods for main effects to examining moderator effects, allowing for tests of whether intervention effects vary for different populations or when employed in different contexts. In addition, we study how the use of individual participant data may increase the sensitivity of NMA for detecting moderator effects, as compared with aggregate data NMA that employs study-level effect sizes in a meta-regression framework. A new NMA diagram is proposed. We also develop a generalized multilevel model for NMA that takes into account within-trial and between-trial heterogeneity and can include participant-level covariates. Within this framework, we present definitions of homogeneity and consistency across trials. A simulation study based on this model is used to assess effects on power to detect both main and moderator effects. Results show that power to detect moderation is substantially greater when applied to individual participant data as compared with study-level effects. We illustrate the use of this method by applying it to data from a classroom-based randomized study that involved two sub-trials, each comparing interventions that were contrasted with separate control groups. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26841368 TI - Third Entrainment Criterion in Wide QRS Tachycardia: Ventricular Tachycardia or Antidromic Atrioventricular Reentrant Tachycardia? PMID- 26841369 TI - Consent and confidentiality in the light of recent demands for data sharing. AB - Many attempts have been made to formalize ethical requirements for research. Among the most prominent mechanisms are informed consent requirements and data protection regimes. These mechanisms, however, sometimes appear as obstacles to research. In this opinion paper, we critically discuss conventional approaches to research ethics that emphasize consent and data protection. Several recent debates have highlighted other important ethical issues and underlined the need for greater openness in order to uphold the integrity of health-related research. Some of these measures, such as the sharing of individual-level data, pose problems for standard understandings of consent and privacy. Here, we argue that these interpretations tend to be overdemanding: They do not really protect research subjects and they hinder the research process. Accordingly, we suggest another way of framing these requirements. Individual consent must be situated alongside the wider distribution of knowledge created when the actions, commitments, and procedures of researchers and their institutions are opened to scrutiny. And instead of simply emphasizing privacy or data protection, we should understand confidentiality as a principle that facilitates the sharing of information while upholding important safeguards. Consent and confidentiality belong to a broader set of safeguards and procedures to uphold the integrity of the research process. PMID- 26841370 TI - Understanding Health Research Ethics in Nepal. AB - Unlike other countries in South Asia, in Nepal research in the health sector has a relatively recent history. Most health research activities in the country are sponsored by international collaborative assemblages of aid agencies and universities. Data from Nepal Health Research Council shows that, officially, 1,212 health research activities have been carried out between 1991 and 2014. These range from addressing immediate health problems at the country level through operational research, to evaluations and programmatic interventions that are aimed at generating evidence, to more systematic research activities that inform global scientific and policy debates. Established in 1991, the Ethical Review Board of the Nepal Health Research Council (NHRC) is the central body that has the formal regulating authority of all the health research activities in country, granted through an act of parliament. Based on research conducted between 2010 and 2013, and a workshop on research ethics that the authors conducted in July 2012 in Nepal as a part of the on-going research, this article highlights the emerging regulatory and ethical fields in this low-income country that has witnessed these increased health research activities. Issues arising reflect this particular political economy of research (what constitutes health research, where resources come from, who defines the research agenda, culture of contract research, costs of review, developing Nepal's research capacity, through to the politics of publication of data/findings) and includes questions to emerging regulatory and ethical frameworks. PMID- 26841371 TI - Optical diagnosis of colorectal neoplasia: A Western perspective. AB - Optical diagnosis is an emerging paradigm in Western endoscopic practice for the colonoscopic management of diminutive polyps, and includes two complementary clinical strategies: 'resect and discard', in which diminutive high-confidence adenomas are identified, and then removed and discarded without pathological assessment; and 'diagnose and leave', where diminutive high-confidence hyperplastic polyps are identified in the rectosigmoid and then left without resection or biopsy. Like other aspects of colonoscopy performance, adoption of optical diagnosis in Western practice is limited by operator dependency and variation in clinical effectiveness. There is substantial potential for optical diagnosis of colorectal neoplasia during colonoscopy to alleviate the rising costs of health care in the West. However, operator dependence in diagnostic performance together with critical system factors such as informed consent, credentialing, medical legal support and reimbursement incentives must be overcome before optical diagnosis of diminutive lesions is considered for widespread adoption in Western clinical practice. PMID- 26841372 TI - CD49f promotes proliferation of male dairy goat germline stem cells. AB - OBJECTIVES: CD49f enhances multipotency and maintains stemness in embryonic stem cells (ESCs), however, whether it would be effective in mGSCs has remained unclear. Moreover, better standards for mGSC enrichment and purification are necessary. The present study was conducted to determine roles of CD49f in mGSC enrichment and regulation. MATERIALS AND METHODS: CD49f expression patterns were investigated in dairy goats. CD49f positive cells were purified and enriched using magnetic-activated cell sorting (MACS), and characteristics of the cultured cells were assayed using alkaline phosphatase (AP) analysis, quantitative real time PCR (QRT-PCR) and immunofluorescence analysis. Furthermore, the exogenous CD49f gene was transfected into mGSCs and its effects were analysed. RESULTS: CD49f was found to be conserved in both mRNA and amino acid sequences and that it was an efficient marker for dairy goat mGSC identification, enrichment and purification. CD49f positive cells expressed higher levels of mGSC-specific markers, and proliferated faster than CD49f negative cells. Overexpression CD49f promoted proliferation of dairy goat mGSCs, and Oct4 expression was upregulated; histone H3-lysine 9 dimethylation (H3K9me2) was reduced. CONCLUSIONS: Taken together, our data suggest that CD49f plays novel and dynamic roles in regulating maintenance of pluripotency in mGSCs via Oct4 crosstalk and histone methylation dynamics,which may provide new solutions for mGSCs stability in vitro. PMID- 26841373 TI - Single, very low dose (0.03 mg) of recombinant human thyrotropin (rhTSH) effectively increases radioiodine uptake in the I-131 treatment of large nontoxic multinodular goiter. AB - BACKGROUND: Radioiodine therapy (RIT) in patients with large nontoxic multinodular goiter (MNG) recently becomes more common method in comparison to surgery (especially in elderly patients and with contraindications because of severe chronic diseases other systems). Repeatedly low thyroid radioactive iodine uptake (RAIU) decreases effectiveness of RIT or makes it impossible. The recombinant human thyrotropin can increase RAIU and improve the results of RIT. THE AIM OF THE STUDY: was to assess the influence of a single very low dose (0.03 mg) of rhTSH on RAIU and thyroid function in euthyroid (MNG-EU) and subclinical hyperthyroid (MNG-SC) patients with a large multinodular goiter. MATERIAL AND METHODS: 40 patients (14 male, 26 female, age 57-80 yr) with large non-toxic MNG over 80 grams and with baseline RAIU < 40% were included into the double-blind randomized study and divided into two groups: rhTSH-group and control group. First group received the single intramuscular injection of 0.03 mg rhTSH and the second received placebo. The RAIU were measured 24 and 48 hours after the rhTSH and then all the patients were administered therapeutic doses of I-131. TSH and free thyroxine levels were measured at 1st and 2nd day after the injection of rhTSH and later, at 4 and 8 weeks after the RIT. RESULTS: The mean RAIU increased significantly from 30.44 +/- 7.4% to 77.22 +/- 8.7% (p < 0.001). There were no statistically significant differences in RAIU between euthyroid (MNG-EU) and subclinically hyperthyroid (MNG-SC) patients. The peak of serum TSH was noticed 24 hours after rhTSH injection and in MNG-EU patients it has remained within normal range, similarly as fT4. In the MNG-SC group the administration of rhTSH resulted in a significant increase in the TSH values after 24 hours, whose mean level slightly exceeded the upper limit of the normal range with normalization at 48 hours. 8 weeks after the RIT, the TSH and fT4 levels did not exceed the normal range and did not differ in a statistically significant way. CONCLUSIONS: Even the single very low dose of rhTSH increases the values of RAIU in significant way, in euthyroid and subclinically hyperthyroid patients. The administration of rhTSH is well-tolerated. Neoadjuvant administration of a low dose (0.03 mg) of rhTSH before I-131 seems to be an optimal method of management which may increase the effectiveness of RIT and decrease the exposure of the patients to absorbed doses of ionizing radiation. PMID- 26841374 TI - Comparison of planar DMSA scan with an evaluation based on SPECT imaging in the split renal function assessment. AB - BACKGROUND: Validation of the 99mTc-DMSA planar scintigraphy accuracy for split renal function assessment and comparison with evaluation based on SPECT imaging both with and without CT attenuation correction. MATERIALS AND METHODS: For split renal function assessment two methods were used: A) planar scintigraphy based on anterior and posterior projections using correction for kidney depth calculated by the geometric mean; B) semi-quantitative evaluation based on SPECT (B1) and attenuation-corrected SPECT/CT (B2) images using locally developed software for kidney segmentation and voxel-based analysis. All three methods were performed with a phantom simulating body including pair of kidneys. For patient study methods A and B1 were applied on a group of 140 children and adolescents with various renal diseases. Renal function ratios were compared both mutually and with physically measured activity ratios in the phantom. RESULTS: Method A provided results which were closest to measured reference values (average absolute difference of 0.9 percentage points [pp]). Method B1 was noticeably worse (2.1pp), whereas attenuation correction (B2) improved tomography results considerably (1.3 pp). The superiority of planar imaging could be caused among others by differences in creation of planar range of interest compared to tomographic volume of interest. However all the differences were under the threshold of any clinical importance. The comparison between method A and B1 based on patient study also showed differences mostly of none clinical importance. CONCLUSION: Routine evaluation of split renal function using planar technique with correction of the kidney depth is at least equivalent to tomographic evaluation, and there is no need to update the established clinical practice. PMID- 26841375 TI - Free thyroxine in needle washout after fine needle aspiration biopsy of toxic thyroid nodules. AB - The main diagnostic tool for toxic adenomas (TA) is radionuclide imaging indicated in patients with evidence of thyroid nodules in combination with thyrotoxic syndrome. Thyroid ultrasound and fine-needle aspiration biopsy (FNAB) are widely used for the valuation of thyroid masses. There is no literature data concerning the utility of FNAB and related tests for the diagnosis of hyperfunctioning thyroid nodules. The purpose of this study is to determine the levels of free thyroxine (FT4) in the needle washout after FNAB of hot thyroid nodules. The results of our study show that the FT4 levels in needle washout from TA were significantly higher than the surrounding parenchyma and correlated with the hormonal changes in patients with thyroid hyperfunctioning nodules. Further studies on a large number of patients are needed to refine the diagnostic value of this method and evaluate its importance in quantitative risk assessment of thyroid autonomy. PMID- 26841376 TI - Dual-time point 18FDG-PET/CT imaging may be useful in assessing local recurrent disease in high grade bone and soft tissue sarcoma. AB - BACKGROUND: Sarcomas comprise 1% of malignant tumors in adults but represent a significant diagnostic and therapeutic challenge. Molecular imaging with 18FDG PET/CT is a powerful modality in oncology. Its use for initial assessment, evaluation of response to therapy and recurrent disease in most tumors is essential for therapeutic decisions. Its indication in sarcomas is still controversial. One of the indications for PET/CT in sarcomas is detection of recurrences. Nowadays magnetic resonance tomography (MRT) has a crucial role in identification of local recurrences in soft tissue and bone sarcoma. 18FDG-PET/CT may serve as a complementary method. Dual time point imaging (DTPI) has been studied for most tumors as a method for differentiating benign from malignant lesions. There is limited data on DTPI in sarcomas. Therefore we studied prospectively patients with suspected local recurrences in the treated area and used DTPI as a method for differentiating benign from malignant tissue. THE AIM: of this study was to evaluate the ability of dual-time point PET/CT to enhance sensitivity, specificity, PPV, NPV and accuracy of 18FDG PET/CT in high grade and low grade sarcomas. MATERIAL AND METHODS: We conducted a dual-time PET/CT in 15 patients with suspected locally recurrent disease. The delayed scan was conducted on the 120th min in the suspected region. The interpretation of PET/CT was made both upon CT scan and metabolic scans. The percentage change over time per lesion was calculated (%DSUV). The increase in SUVmax with %DSUV > 10% in the late scanning was considered as indicative for malignancy. We assessed the sensitivity, specificity, accuracy, positive and negative predicting value of the interpretation of PET/CT at 60 min and 120 min. All of the patients were followed up for a period of 1-3 years after our examination, either with histologic results, or with an MRT scans. RESULTS: The received sensitivity, specificity and accuracy of 18FDG PET/CT interpretation at 120 min in high grade sarcomas were respectively 100%, 80% and 89%. By comparison, in low grade tumors at 120 min scan, these parameters were 50%, 75% and 66%. CONCLUSION: These preliminary data suggests that dual-time imaging in sarcomas improves sensitivity and accuracy in identification of local recurrent disease in high grade sarcomas and have limited role in low grade sarcomas. Further research is necessary to confirm these results. PMID- 26841377 TI - Role of 18F-FDG PET/CT in the diagnosis of inflammatory and infectious vascular disease. AB - This review article discusses the utility of 18F-FDG PET/CT in diagnosis and management of vascular disease. We stress usefulness of this method in large vessel inflammation and infection. In our work we based on the literature analysis and clinical cases diagnosed in our institution by use of 18F-FDG PET/CT. The literature exploration was focusing on vascular inflammation and infections and 18-FDG PET. The search was performed on PubMed database and cross referencing. We present the practical review with several images of vascular diseases like: Takayasu arteritis, giant cell arteritis, vascular graft infections, abdominal aortic aneurysm infections and cases of aortitis and periaortitis. From this work inflammation associated with atheromatic process and vulnerable atherosclerotic plaque we excluded. 18F-FGD PET/CT is a sensitive metabolic, reliable, non-invasive imaging modality suitable for diagnosis and follow-up of inflammation and infections in vascular system. PMID- 26841378 TI - PET/MR - a rapidly growing technique of imaging in oncology and neurology. AB - INTRODUCTION: The combination of positron emission tomography (PET) and magnetic resonance (MR) has become a subject of interest for researchers in the recent several years. Positron emission tomography in combination with magnetic resonance (PET/MR) is the most recent imaging technique classified in the so called hybrid systems category. AIM: This review briefly discusses the development history of PET/MR scanners, the principle of their operation, of tandem systems, as well as fully integrated devices. Further, it summarizes recent reports on the application of PET/MR scans and their possible future role in oncological and non-oncological diagnostics. CONCLUSIONS: Recent reports regarding the application of PET/MR scanners show huge potential of simultaneously received images, which exceed the advantages of either of those scans used separately. However, the results so far remain uncertain and require further investigations, especially in terms of clinical studies, not only for scientific purposes. PMID- 26841380 TI - When Interpolation-Induced Reflection Artifact Meets Time-Frequency Analysis. AB - OBJECTIVE: While extracting the temporal dynamical features based on the time frequency analyses, like the reassignment and synchrosqueezing transform, attracts more and more interest in biomedical data analysis, we should be careful about artifacts generated by interpolation schemes, in particular when the sampling rate is not significantly higher than the frequency of the oscillatory component we are interested in. METHODS: We formulate the problem called the reflection effect and provide a theoretical justification of the statement. We also show examples in the anesthetic depth analysis with clear but undesirable artifacts. RESULTS: The artifact associated with the reflection effect exists not only theoretically but practically as well. Its influence is pronounced when we apply the time-frequency analyses to extract the time-varying dynamics hidden inside the signal. CONCLUSION: We have to carefully deal with the artifact associated with the reflection effect by choosing a proper interpolation scheme. PMID- 26841379 TI - The Comparison of Matching Methods Using Different Measures of Balance: Benefits and Risks Exemplified within a Study to Evaluate the Effects of German Disease Management Programs on Long-Term Outcomes of Patients with Type 2 Diabetes. AB - OBJECTIVE: To present a case study on how to compare various matching methods applying different measures of balance and to point out some pitfalls involved in relying on such measures. DATA SOURCES: Administrative claims data from a German statutory health insurance fund covering the years 2004-2008. STUDY DESIGN: We applied three different covariance balance diagnostics to a choice of 12 different matching methods used to evaluate the effectiveness of the German disease management program for type 2 diabetes (DMPDM2). We further compared the effect estimates resulting from applying these different matching techniques in the evaluation of the DMPDM2. PRINCIPAL FINDINGS: The choice of balance measure leads to different results on the performance of the applied matching methods. Exact matching methods performed well across all measures of balance, but resulted in the exclusion of many observations, leading to a change of the baseline characteristics of the study sample and also the effect estimate of the DMPDM2. All PS-based methods showed similar effect estimates. Applying a higher matching ratio and using a larger variable set generally resulted in better balance. Using a generalized boosted instead of a logistic regression model showed slightly better performance for balance diagnostics taking into account imbalances at higher moments. CONCLUSION: Best practice should include the application of several matching methods and thorough balance diagnostics. Applying matching techniques can provide a useful preprocessing step to reveal areas of the data that lack common support. The use of different balance diagnostics can be helpful for the interpretation of different effect estimates found with different matching methods. PMID- 26841381 TI - Improved Noncoherent UWB Receiver for Implantable Biomedical Devices. AB - GOAL: The purpose of this paper is to describe a novel noncoherent receiver architecture to improve the error performance of impulse-radio ultrawideband (IR UWB) in bioimplanted devices. IR-UWB receivers based on energy detection are popular in biomedical applications owing to the low implementation cost/complexity and the high data rates that UWB can potentially support. Implanted devices suffer from severe frequency-dependent attenuation due to human blood and tissues, while most receivers in the literature are designed based on commonly used indoor wireless channel models. METHOD: We propose a novel receiver design that is based on judiciously combining the energies in different bands of the signal spectrum with a weighted linear combiner. We derive the optimum coefficients of the combiner. RESULTS: The receiver retains almost all of the advantages of a conventional noncoherent detector, but can also compensate for attenuation properties of blood/tissue. The receiver design can be adapted to different implantation depths by simply varying the combiner weights. The receiver can also be considered to be a simple form of equalizer for noncoherent reception. Our simulations show about 2-dB improvement over other commonly used receivers. SIGNIFICANCE: This receiver design is significant in that it can enhance critical battery life of implanted transmitters. PMID- 26841382 TI - Effects of Temporal Congruity Between Auditory and Visual Stimuli Using Rapid Audio-Visual Serial Presentation. AB - GOAL: Combining visual and auditory stimuli in event-related potential (ERP) based spellers gained more attention in recent years. Few of these studies notice the difference of ERP components and system efficiency caused by the shifting of visual and auditory onset. Here, we aim to study the effect of temporal congruity of auditory and visual stimuli onset on bimodal brain-computer interface (BCI) speller. METHODS: We designed five visual and auditory combined paradigms with different visual-to-auditory delays (-33 to +100 ms). Eleven participants attended in this study. ERPs were acquired and aligned according to visual and auditory stimuli onset, respectively. ERPs of Fz, Cz, and PO7 channels were studied through the statistical analysis of different conditions both from visual aligned ERPs and audio-aligned ERPs. Based on the visual-aligned ERPs, classification accuracy was also analyzed to seek the effects of visual-to auditory delays. RESULTS: The latencies of ERP components depended mainly on the visual stimuli onset. Auditory stimuli onsets influenced mainly on early component accuracies, whereas visual stimuli onset determined later component accuracies. The latter, however, played a dominate role in overall classification. SIGNIFICANCE: This study is important for further studies to achieve better explanations and ultimately determine the way to optimize the bimodal BCI application. PMID- 26841384 TI - Computing Cyclotorsion in Refractive Cataract Surgery. AB - GOAL: In refractive surgery, astigmatism-correcting treatments are generally planned with the aid of some diagnostic imaging device and often executed by some computer guided laser system. In the transition from sitting down at a diagnostic device to lying down beneath a laser system, a phenomenon known as cyclotorsion (rotation of the eye within the socket) occurs. Hence, registration between lasers and diagnostic devices is necessary. The purpose of this paper is to present a newly developed algorithm that accomplishes robust registration using images of the patient's iris in the context of laser-assisted cataract surgery, and evaluate its efficacy. METHODS: The proposed iris registration algorithm was tested on real cataract patient images obtained from commercially available devices. Accuracy was measured against manual registrations performed by trained humans. Conservative bounds on success and failure rates were computed using novel statistical methods. RESULTS: The algorithm better approximated the cyclotorsion as averaged over manual measurements from three trained humans than any of the three individual humans, with a 95% tolerance interval of +/-1.36( degrees ) . In addition, a success rate >= 99.0% was observed for an acceptance threshold setting that allowed for a false registration rate <= 1.00*10(-3)%. CONCLUSION: The proposed iris registration algorithm accurately and consistently compensates for cyclotorsion in laser-assisted cataract surgery. SIGNIFICANCE: This paper details the first algorithm to be used for iris registration in laser assisted cataract surgery. Enabling surgeons to make use of this algorithm in real surgeries is expected to have a significant impact on astigmatism management in cataract surgery. PMID- 26841385 TI - Epileptic Seizure Prediction Based on Multivariate Statistical Process Control of Heart Rate Variability Features. AB - OBJECTIVE: The present study proposes a new epileptic seizure prediction method through integrating heart rate variability (HRV) analysis and an anomaly monitoring technique. METHODS: Because excessive neuronal activities in the preictal period of epilepsy affect the autonomic nervous systems and autonomic nervous function affects HRV, it is assumed that a seizure can be predicted through monitoring HRV. In the proposed method, eight HRV features are monitored for predicting seizures by using multivariate statistical process control, which is a well-known anomaly monitoring method. RESULTS: We applied the proposed method to the clinical data collected from 14 patients. In the collected data, 8 patients had a total of 11 awakening preictal episodes and the total length of interictal episodes was about 57 h. The application results of the proposed method demonstrated that seizures in ten out of eleven awakening preictal episodes could be predicted prior to the seizure onset, that is, its sensitivity was 91%, and its false positive rate was about 0.7 times per hour. CONCLUSION: This study proposed a new HRV-based epileptic seizure prediction method, and the possibility of realizing an HRV-based epileptic seizure prediction system was shown. SIGNIFICANCE: The proposed method can be used in daily life, because the heart rate can be measured easily by using a wearable sensor. PMID- 26841386 TI - Morphological Feature Extraction From a Continuous Intracranial Pressure Pulse via a Peak Clustering Algorithm. AB - OBJECTIVE: An increase in intracranial pressure (ICP) is frequently observed in patients with severe traumatic brain injury (TBI). The information derived from the observation of temporal changes in the mean ICP is insufficient for assessment of the compensatory reserve of the injured brain. This assessment can be achieved via continuous morphological analysis of the pulse waveform of the ICP. METHODS: Continuous arterial blood pressure (ABP) and ICP recordings from 292 TBI patients were analyzed. The algorithm extracted morphological landmarks (peaks, troughs, and flats) from the ICP. Among the extracted peaks, P1, P2, and P3 were assigned through peak clustering. The performance of the proposed method was validated through a comparison of the algorithm-defined peaks and those manually identified by experienced observers. RESULTS: The proposed algorithm successfully identified the three distinguishing peaks of the ICP with satisfactory accuracy (95.3%, 87.8%, and 87.5% for P1, P2, and P3, respectively), even from minimally filtered raw signals. CONCLUSION: The algorithm extracted the morphological features from both ABP and ICP recordings with high accuracy. SIGNIFICANCE: The ABP and ICP pulse waveforms can be simultaneously analyzed in real time using the proposed algorithm. The morphological features from these signals may aid the continuous care of patients with TBI. PMID- 26841387 TI - Efficient, Non-Iterative Estimator for Imaging Contrast Agents With Spectral X Ray Detectors. AB - An estimator to image contrast agents and body materials with x-ray spectral measurements is described. The estimator is usable with the three or more basis functions that are required to represent the attenuation coefficient of high atomic number materials. The estimator variance is equal to the Cramer-Rao lower bound (CRLB) and it is unbiased. Its parameters are computed from measurements of a calibration phantom with the clinical x-ray system and it is non-iterative. The estimator is compared with an iterative maximum likelihood estimator. The estimator first computes a linearized maximum likelihood estimate of the line integrals of the basis set coefficients. Corrections for errors in the initial estimates are computed by interpolation with calibration phantom data. The final estimate is the initial estimate plus the correction. The performance of the estimator is measured using a Monte Carlo simulation. Random photon counting with pulse height analysis data are generated. The mean squared errors of the estimates are compared to the CRLB. The random data are also processed with an iterative maximum likelihood estimator. Previous implementations of iterative estimators required advanced physics instruments not usually available in clinical institutions. The estimator mean squared error is essentially equal to the CRLB. The estimator outputs are close to those of the iterative estimator but the computation time is approximately 180 times shorter. The estimator is efficient and has advantages over alternate approaches such as iterative estimators. PMID- 26841388 TI - Kernel Bundle Diffeomorphic Image Registration Using Stationary Velocity Fields and Wendland Basis Functions. AB - In this paper, we propose a multi-scale, multi-kernel shape, compactly supported kernel bundle framework for stationary velocity field-based image registration (Wendland kernel bundle stationary velocity field, wKB-SVF). We exploit the possibility of directly choosing kernels to construct a reproducing kernel Hilbert space (RKHS) instead of imposing it from a differential operator. The proposed framework allows us to minimize computational cost without sacrificing the theoretical foundations of SVF-based diffeomorphic registration. In order to recover deformations occurring at different scales, we use compactly supported Wendland kernels at multiple scales and orders to parameterize the velocity fields, and the framework allows simultaneous optimization over all scales. The performance of wKB-SVF is extensively compared to the 14 non-rigid registration algorithms presented in a recent comparison paper. On both MGH10 and CUMC12 datasets, the accuracy of wKB-SVF is improved when compared to other registration algorithms. In a disease-specific application for intra-subject registration, atrophy scores estimated using the proposed registration scheme separates the diagnostic groups of Alzheimer's and normal controls better than the state-of-the art segmentation technique. Experimental results show that wKB-SVF is a robust, flexible registration framework that allows theoretically well-founded and computationally efficient multi-scale representation of deformations and is equally well-suited for both inter- and intra-subject image registration. PMID- 26841389 TI - Multiple Kernel Point Set Registration. AB - The finite Gaussian mixture model with kernel correlation is a flexible tool that has recently received attention for point set registration. While there are many algorithms for point set registration presented in the literature, an important issue arising from these studies concerns the mapping of data with nonlinear relationships and the ability to select a suitable kernel. Kernel selection is crucial for effective point set registration. We focus here on multiple kernel point set registration. We make several contributions in this paper. First, each observation is modeled using the Student's t-distribution, which is heavily tailed and more robust than the Gaussian distribution. Second, by automatically adjusting the kernel weights, the proposed method allows us to prune the ineffective kernels. This makes the choice of kernels less crucial. After parameter learning, the kernel saliencies of the irrelevant kernels go to zero. Thus, the choice of kernels is less crucial and it is easy to include other kinds of kernels. Finally, we show empirically that our model outperforms state-of-the art methods recently proposed in the literature. PMID- 26841390 TI - DeepTrack: Learning Discriminative Feature Representations Online for Robust Visual Tracking. AB - Deep neural networks, albeit their great success on feature learning in various computer vision tasks, are usually considered as impractical for online visual tracking, because they require very long training time and a large number of training samples. In this paper, we present an efficient and very robust tracking algorithm using a single convolutional neural network (CNN) for learning effective feature representations of the target object in a purely online manner. Our contributions are multifold. First, we introduce a novel truncated structural loss function that maintains as many training samples as possible and reduces the risk of tracking error accumulation. Second, we enhance the ordinary stochastic gradient descent approach in CNN training with a robust sample selection mechanism. The sampling mechanism randomly generates positive and negative samples from different temporal distributions, which are generated by taking the temporal relations and label noise into account. Finally, a lazy yet effective updating scheme is designed for CNN training. Equipped with this novel updating algorithm, the CNN model is robust to some long-existing difficulties in visual tracking, such as occlusion or incorrect detections, without loss of the effective adaption for significant appearance changes. In the experiment, our CNN tracker outperforms all compared state-of-the-art methods on two recently proposed benchmarks, which in total involve over 60 video sequences. The remarkable performance improvement over the existing trackers illustrates the superiority of the feature representations, which are learned purely online via the proposed deep learning framework. PMID- 26841391 TI - Ellipse Fitting Using the Finite Rate of Innovation Sampling Principle. AB - Standard approaches for ellipse fitting are based on the minimization of algebraic or geometric distance between the given data and a template ellipse. When the data are noisy and come from a partial ellipse, the state-of-the-art methods tend to produce biased ellipses. We rely on the sampling structure of the underlying signal and show that the x - and y -coordinate functions of an ellipse are finite-rate-of-innovation (FRI) signals, and that their parameters are estimable from partial data. We consider both uniform and nonuniform sampling scenarios in the presence of noise and show that the data can be modeled as a sum of random amplitude-modulated complex exponentials. A low-pass filter is used to suppress noise and approximate the data as a sum of weighted complex exponentials. The annihilating filter used in FRI approaches is applied to estimate the sampling interval in the closed form. We perform experiments on simulated and real data, and assess both objective and subjective performances in comparison with the state-of-the-art ellipse fitting methods. The proposed method produces ellipses with lesser bias. Furthermore, the mean-squared error is lesser by about 2 to 10 dB. We show the applications of ellipse fitting in iris images starting from partial edge contours, and to free-hand ellipses drawn on a touch screen tablet. PMID- 26841392 TI - Nonconvex Nonsmooth Low Rank Minimization via Iteratively Reweighted Nuclear Norm. AB - The nuclear norm is widely used as a convex surrogate of the rank function in compressive sensing for low rank matrix recovery with its applications in image recovery and signal processing. However, solving the nuclear norm-based relaxed convex problem usually leads to a suboptimal solution of the original rank minimization problem. In this paper, we propose to use a family of nonconvex surrogates of L0-norm on the singular values of a matrix to approximate the rank function. This leads to a nonconvex nonsmooth minimization problem. Then, we propose to solve the problem by an iteratively re-weighted nuclear norm (IRNN) algorithm. IRNN iteratively solves a weighted singular value thresholding problem, which has a closed form solution due to the special properties of the nonconvex surrogate functions. We also extend IRNN to solve the nonconvex problem with two or more blocks of variables. In theory, we prove that the IRNN decreases the objective function value monotonically, and any limit point is a stationary point. Extensive experiments on both synthesized data and real images demonstrate that IRNN enhances the low rank matrix recovery compared with the state-of-the art convex algorithms. PMID- 26841393 TI - No-Reference Depth Assessment Based on Edge Misalignment Errors for T+D Images. AB - The quality of depth is crucial in all depth-based applications. Unfortunately, the error-free ground truth is often unattainable for depth. Therefore, no reference quality assessment is very much desired. This paper presents a novel depth quality assessment scheme that is completely different from conventional approaches. In particular, this scheme focuses on depth edge misalignment errors in texture-plus-depth (T + D) images and develops a robust method to detect them. Based on the detected misalignments, a no-reference metric is calculated to evaluate the quality of depth maps. In the proposed scheme, misalignments are detected by matching texture and depth edges through three constraints: 1) spatial similarity; 2) edge orientation similarity; and 3) segment length similarity. Furthermore, the matching is performed on edge segments instead of individual pixels, which enables robust edge matching. Experimental results demonstrate that the proposed scheme can detect misalignment errors accurately. The proposed no-reference depth quality metric is highly consistent with the full reference metric, and is also well-correlated with the quality of synthesized virtual views. Moreover, the proposed scheme can also use the detected edge misalignments to facilitate depth enhancement in various practical texture-plus depth-based applications. PMID- 26841394 TI - Single-Image Super-Resolution Using Active-Sampling Gaussian Process Regression. AB - As well known, Gaussian process regression (GPR) has been successfully applied to example learning-based image super-resolution (SR). Despite its effectiveness, the applicability of a GPR model is limited by its remarkably computational cost when a large number of examples are available to a learning task. For this purpose, we alleviate this problem of the GPR-based SR and propose a novel example learning-based SR method, called active-sampling GPR (AGPR). The newly proposed approach employs an active learning strategy to heuristically select more informative samples for training the regression parameters of the GPR model, which shows significant improvement on computational efficiency while keeping higher quality of reconstructed image. Finally, we suggest an accelerating scheme to further reduce the time complexity of the proposed AGPR-based SR by using a pre-learned projection matrix. We objectively and subjectively demonstrate that the proposed method is superior to other competitors for producing much sharper edges and finer details. PMID- 26841395 TI - Simple to Complex Transfer Learning for Action Recognition. AB - Recognizing complex human actions is very challenging, since training a robust learning model requires a large amount of labeled data, which is difficult to acquire. Considering that each complex action is composed of a sequence of simple actions which can be easily obtained from existing data sets, this paper presents a simple to complex action transfer learning model (SCA-TLM) for complex human action recognition. SCA-TLM improves the performance of complex action recognition by leveraging the abundant labeled simple actions. In particular, it optimizes the weight parameters, enabling the complex actions to be learned to be reconstructed by simple actions. The optimal reconstruct coefficients are acquired by minimizing the objective function, and the target weight parameters are then represented as a combination of source weight parameters. The main advantage of the proposed SCA-TLM compared with existing approaches is that we exploit simple actions to recognize complex actions instead of only using complex actions as training samples. To validate the proposed SCA-TLM, we conduct extensive experiments on two well-known complex action data sets: 1) Olympic Sports data set and 2) UCF50 data set. The results show the effectiveness of the proposed SCA-TLM for complex action recognition. PMID- 26841396 TI - Recognition of Images Degraded by Gaussian Blur. AB - In this paper, we propose a new theory of invariants to Gaussian blur. We introduce a notion of a primordial image as a canonical form of all Gaussian blur equivalent images. The primordial image is defined in spectral domain by means of projection operators. We prove that the moments of the primordial image are invariant to Gaussian blur and we derive recursive formulas for their direct computation without actually constructing the primordial image itself. We show how to extend their invariance also to image rotation. The application of these invariants is in blur-invariant image comparison and recognition. In the experimental part, we perform an exhaustive comparison with two main competitors: 1) the Zhang distance and 2) the local phase quantization. PMID- 26841398 TI - Can Twitter Save Lives? A Broad-Scale Study on Visual Social Media Analytics for Public Safety. AB - The use of social media monitoring for public safety is on the brink of commercialization and practical adoption. To close the gap between research and application, this paper presents results of a two-phase study on visual analytics of social media for public safety. For the first phase, we conducted a large field study, in which 29 practitioners from disaster response and critical infrastructure management were asked to investigate crisis intelligence tasks based on Twitter data recorded during the 2013 German Flood. To this end, the ScatterBlogs visual analytics system, a platform that provides reference implementations of tools and techniques popular in research, was given to them as an integrated toolbox. We reviewed the domain experts' individual performances with the system as well as their comments about the usefulness of techniques. In the second phase, we built on this feedback about ScatterBlogs in order to sketch out a system and create additional tools specifically adapted to the collected requirements. The performance of the old lab prototype is finally compared against the re-design in a controlled user study. PMID- 26841399 TI - Solving the Fluid Pressure Poisson Equation Using Multigrid-Evaluation and Improvements. AB - In many numerical simulations of fluids governed by the incompressible Navier Stokes equations, the pressure Poisson equation needs to be solved to enforce mass conservation. Multigrid solvers show excellent convergence in simple scenarios, yet they can converge slowly in domains where physically separated regions are combined at coarser scales. Moreover, existing multigrid solvers are tailored to specific discretizations of the pressure Poisson equation, and they cannot easily be adapted to other discretizations. In this paper we analyze the convergence properties of existing multigrid solvers for the pressure Poisson equation in different simulation domains, and we show how to further improve the multigrid convergence rate by using a graph-based extension to determine the coarse grid hierarchy. The proposed multigrid solver is generic in that it can be applied to different kinds of discretizations of the pressure Poisson equation, by using solely the specification of the simulation domain and pre-assembled computational stencils. We analyze the proposed solver in combination with finite difference and finite volume discretizations of the pressure Poisson equation. Our evaluations show that, despite the common assumption, multigrid schemes can exploit their potential even in the most complicated simulation scenarios, yet this behavior is obtained at the price of higher memory consumption. PMID- 26841397 TI - Robust w-Estimators for Cryo-EM Class Means. AB - A critical step in cryogenic electron microscopy (cryo-EM) image analysis is to calculate the average of all images aligned to a projection direction. This average, called the class mean, improves the signal-to-noise ratio in single particle reconstruction. The averaging step is often compromised because of the outlier images of ice, contaminants, and particle fragments. Outlier detection and rejection in the majority of current cryo-EM methods are done using cross correlation with a manually determined threshold. Empirical assessment shows that the performance of these methods is very sensitive to the threshold. This paper proposes an alternative: a w-estimator of the average image, which is robust to outliers and which does not use a threshold. Various properties of the estimator, such as consistency and influence function are investigated. An extension of the estimator to images with different contrast transfer functions is also provided. Experiments with simulated and real cryo-EM images show that the proposed estimator performs quite well in the presence of outliers. PMID- 26841401 TI - Parametric Human Body Reconstruction Based on Sparse Key Points. AB - We propose an automatic parametric human body reconstruction algorithm which can efficiently construct a model using a single Kinect sensor. A user needs to stand still in front of the sensor for a couple of seconds to measure the range data. The user's body shape and pose will then be automatically constructed in several seconds. Traditional methods optimize dense correspondences between range data and meshes. In contrast, our proposed scheme relies on sparse key points for the reconstruction. It employs regression to find the corresponding key points between the scanned range data and some annotated training data. We design two kinds of feature descriptors as well as corresponding regression stages to make the regression robust and accurate. Our scheme follows with dense refinement where a pre-factorization method is applied to improve the computational efficiency. Compared with other methods, our scheme achieves similar reconstruction accuracy but significantly reduces runtime. PMID- 26841402 TI - Myoelectric Control for Adaptable Biomechanical Energy Harvesting. AB - We have designed and tested a myoelectric controller that automatically adapts energy harvesting from the motion of leg joints to match the power available in different walking conditions. To assist muscles in performing negative mechanical work, the controller engages power generation only when estimated joint mechanical power is negative. When engaged, the controller scales its resistive torque in proportion to estimated joint torque, thereby automatically scaling electrical power generation in proportion to the available mechanical power. To produce real-time estimates of joint torque and mechanical power, the controller leverages a simple model that predicts these variables from measured muscle activity and joint angular velocity. We first tested the model using available literature data for a range of walking speeds and found that estimates of knee joint torque and power well match the corresponding literature profiles (torque R(2): 0.73-0.92; power R(2): 0.60-0.94). We then used human subject experiments to test the performance of the entire controller. Over a range of steady state walking speeds and inclines, as well as a number of non-steady state walking conditions, the myoelectric controller accurately identified when the knee generated negative mechanical power, and automatically adjusted the magnitude of electrical power generation. PMID- 26841403 TI - Immobilization of Bovine Serum Albumin Upon Multiwall Carbon Nanotube for High Speed Humidity Sensing Application. AB - We present a high-speed humidity sensor based on immobilization of bovine serum albumin upon multiwall carbon nanotube (IBC). A simple and versatile drop casting technique was employed to make the humidity sensor using novel material IBC at room temperature. IBC was synthesized using easy solution process technique. The working principle of the IBC humidity sensor depends upon the variation of output current or conductance with the exposure of different humidity level. Humidity sensing properties of our device is explained on the basis of charge transfer from water molecules to IBC and bovine serum albumin to multiwall carbon nanotube (MWCNT). Our sensor exhibits faster response time around 1.2 s and recovery time 1.5 s respectively. PMID- 26841409 TI - Authentication of Medicines Using Nuclear Quadrupole Resonance Spectroscopy. AB - The production and sale of counterfeit and substandard pharmaceutical products, such as essential medicines, is an important global public health problem. We describe a chemometric passport-based approach to improve the security of the pharmaceutical supply chain. Our method is based on applying nuclear quadrupole resonance (NQR) spectroscopy to authenticate the contents of medicine packets. NQR is a non-invasive, non-destructive, and quantitative radio frequency (RF) spectroscopic technique. It is sensitive to subtle features of the solid-state chemical environment and thus generates unique chemical fingerprints that are intrinsically difficult to replicate. We describe several advanced NQR techniques, including two-dimensional measurements, polarization enhancement, and spin density imaging, that further improve the security of our authentication approach. We also present experimental results that confirm the specificity and sensitivity of NQR and its ability to detect counterfeit medicines. PMID- 26841411 TI - Wireless Fidelity Electromagnetic Field Exposure Monitoring With Wearable Body Sensor Networks. AB - With the breakthrough of the Internet of Things and the steady increase of wireless applications in the daily environment, the assessment of radio frequency electromagnetic field (RF-EMF) exposure is key in determining possible health effects of exposure to certain levels of RF-EMF. This paper presents the first experimental validation of a novel personal exposimeter system based on a distributed measurement approach to achieve higher measurement quality and lower measurement variability than the commonly used single point measurement approach of existing exposimeters. An important feature of the system is the integration of inertial sensors in order to determine activity and posture during exposure measurements. The system is designed to assess exposure to frequencies within the 389 to 464, 779 to 928 and 2400 to 2483.5 MHz bands using only two transceivers per node. In this study, the 2400 to 2483.5 MHz band is validated. Every node provides antenna diversity for the different bands in order to achieve higher sensitivity at these frequencies. Two AAA batteries power each standalone node and as such determine the node hardware size of this proof of concept (53 mm*25 mm*15 mm) , making it smaller than any other commercially available exposimeter. PMID- 26841412 TI - Graphical Features of Functional Genes in Human Protein Interaction Network. AB - With the completion of the human genome project, it is feasible to investigate large-scale human protein interaction network (HPIN) with complex networks theory. Proteins are encoded by genes. Essential, viable, disease, conserved, housekeeping (HK) and tissue-enriched (TE) genes are functional genes, which are organized and functioned via interaction networks. Based on up-to-date data from various databases or literature, two large-scale HPINs and six subnetworks are constructed. We illustrate that the HPINs and most of the subnetworks are sparse, small-world, scale-free, disassortative and with hierarchical modularity. Among the six subnetworks, essential, disease and HK subnetworks are more densely connected than the others. Statistical analysis on the topological structures of the HPIN reveals that the lethal, the conserved, the HK and the TE genes are with hallmark graphical features. Receiver operating characteristic (ROC) curves indicate that the essential genes can be distinguished from the viable ones with accuracy as high as almost 70%. Closeness, semi-local and eigenvector centralities can distinguish the HK genes from the TE ones with accuracy around 82%. Furthermore, the Venn diagram, cluster dendgrams and classifications of disease genes reveal that some classes of disease genes are with hallmark graphical features, especially for cancer genes, HK disease genes and TE disease genes. The findings facilitate the identification of some functional genes via topological structures. The investigations shed some light on the characteristics of the compete interactome, which have potential implications in networked medicine and biological network control. PMID- 26841414 TI - Analysis and Simple Circuit Design of Double Differential EMG Active Electrode. AB - In this paper we present an analysis of the voltage amplifier needed for double differential (DD) sEMG measurements and a novel, very simple circuit for implementing DD active electrodes. The three-input amplifier that standalone DD active electrodes require is inherently different from a differential amplifier, and general knowledge about its design is scarce in the literature. First, the figures of merit of the amplifier are defined through a decomposition of its input signal into three orthogonal modes. This analysis reveals a mode containing EMG crosstalk components that the DD electrode should reject. Then, the effect of finite input impedance is analyzed. Because there are three terminals, minimum bounds for interference rejection ratios due to electrode and input impedance unbalances with two degrees of freedom are obtained. Finally, a novel circuit design is presented, including only a quadruple operational amplifier and a few passive components. This design is nearly as simple as the branched electrode and much simpler than the three instrumentation amplifier design, while providing robust EMG crosstalk rejection and better input impedance using unity gain buffers for each electrode input. The interference rejection limits of this input stage are analyzed. An easily replicable implementation of the proposed circuit is described, together with a parameter design guideline to adjust it to specific needs. The electrode is compared with the established alternatives, and sample sEMG signals are obtained, acquired on different body locations with dry contacts, successfully rejecting interference sources. PMID- 26841413 TI - A Robust System for Longitudinal Knee Joint Edema and Blood Flow Assessment Based on Vector Bioimpedance Measurements. AB - We present a robust vector bioimpedance measurement system for longitudinal knee joint health assessment, capable of acquiring high resolution static (slowly varying over the course of hours to days) and dynamic (rapidly varying on the order of milli-seconds) bioresistance and bioreactance signals. Occupying an area of 78*90 mm(2) and consuming 0.25 W when supplied with +/-5 V, the front-end achieves a dynamic range of 345 Omega and noise floor of 0.018 mOmegarms (resistive) and 0.055 mOmegarms (reactive) within a bandwidth of 0.1-20 Hz. A microcontroller allows real-time calibration to minimize errors due to environmental variability (e.g., temperature) that can be experienced outside of lab environments, and enables data storage on a micro secure digital card. The acquired signals are then processed using customized physiology-driven algorithms to extract musculoskeletal (edema) and cardiovascular (local blood volume pulse) features from the knee joint. In a feasibility study, we found statistically significant differences between the injured and contralateral static knee impedance measures for two subjects with recent unilateral knee injury compared to seven controls. Specifically, the impedance was lower for the injured knees, supporting the physiological expectations for increased edema and damaged cell membranes. In a second feasibility study, we demonstrate the sensitivity of the dynamic impedance measures with a cold-pressor test, with a 20 mOmega decrease in the pulsatile resistance associated with increased downstream peripheral vascular resistance. The proposed system will serve as a foundation for future efforts aimed at quantifying joint health status continuously during normal daily life. PMID- 26841416 TI - Sparse Principal Component Analysis via Rotation and Truncation. AB - Sparse principal component analysis (sparse PCA) aims at finding a sparse basis to improve the interpretability over the dense basis of PCA, while still covering the data subspace as much as possible. In contrast to most existing work that addresses the problem by adding sparsity penalties on various objectives of PCA, we propose a new method, sparse PCA via rotation and truncation (SPCArt), which finds a rotation matrix and a sparse basis such that the sparse basis approximates the basis of PCA after the rotation. The algorithm of SPCArt consists of three alternating steps: 1) rotating the PCA basis; 2) truncating small entries; and 3) updating the rotation matrix. Its performance bounds are also given. The SPCArt is efficient, with each iteration scaling linearly with the data dimension. Parameter choice is simple, due to explicit physical explanations. We give a unified view to several existing sparse PCA methods and discuss the connections with SPCArt. Some ideas from SPCArt are extended to GPower, a popular sparse PCA algorithm, to address its limitations. Experimental results demonstrate that SPCArt achieves the state-of-the-art performance, along with a good tradeoff among various criteria, including sparsity, explained variance, orthogonality, balance of sparsity among loadings, and computational speed. PMID- 26841419 TI - Triplet Spike Time-Dependent Plasticity in a Floating-Gate Synapse. AB - Synapse plays an important role in learning in a neural network; the learning rules that modify the synaptic strength based on the timing difference between the pre- and postsynaptic spike occurrence are termed spike time-dependent plasticity (STDP) rules. The most commonly used rule posits weight change based on time difference between one presynaptic spike and one postsynaptic spike and is hence termed doublet STDP (D-STDP). However, D-STDP could not reproduce results of many biological experiments; a triplet STDP (T-STDP) that considers triplets of spikes as the fundamental unit has been proposed recently to explain these observations. This paper describes the compact implementation of a synapse using a single floating-gate (FG) transistor that can store a weight in a nonvolatile manner and demonstrates the T-STDP learning rule by modifying drain voltages according to triplets of spikes. We describe a mathematical procedure to obtain control voltages for the FG device for T-STDP and also show measurement results from an FG synapse fabricated in TSMC 0.35-MUm CMOS process to support the theory. Possible very large scale integration implementation of drain voltage waveform generator circuits is also presented with the simulation results. PMID- 26841428 TI - An Integrated Reliability Estimation Approach With Stochastic Filtering and Degradation Modeling for Phased-Mission Systems. AB - Reliability estimation is central to enhance safety, availability, and effectiveness of phased-mission systems (PMSs). With the development of information and sensing technologies, condition monitoring (CM) data are now available in many real-world PMSs, and then a more interesting question: how can we dynamically estimate the reliability of PMSs using the in-situ CM data, is of considerable significance to industrial practitioners. In this paper, using the CM data and degradation data of PMS, we present a novel condition-based approach to resolve this question under dynamic operating scenarios. This paper differs from most existing methods which only consider the static scenario without using real-time information, and estimate the reliability only for a population of PMSs but not for an individual PMS in service. To establish a linkage between the historical data and real-time data of the individual PMS, a stochastic filtering model is first utilized to model the phase duration. As such, the updated estimation of the mission time can be obtained by Bayesian law at each phase. To account for the dependency of the degradation progression of PMS on the mission process, the degradation process of PMS is modeled by a Brownian motion with a mission phase-dependent drift coefficient. The corresponding lifetime is derived and the lifetime distribution of PMS can be updated under Bayesian framework once new information is available. Unique to this paper is the union of the CM data and degradation data of PMS to real-time estimate the mission reliability through the estimated distribution of the mission time in conjunction with the estimated lifetime distribution, in which the estimated lifetime considers the dependency of the degradation rate of PMS on mission phase. The effectiveness of the proposed approach is verified by a numerical simulation and a case study. PMID- 26841424 TI - Unobtrusive Detection of Mild Cognitive Impairment in Older Adults Through Home Monitoring. AB - The early detection of dementias such as Alzheimer's disease can in some cases reverse, stop, or slow cognitive decline and in general greatly reduce the burden of care. This is of increasing significance as demographic studies are warning of an aging population in North America and worldwide. Various smart homes and systems have been developed to detect cognitive decline through continuous monitoring of high risk individuals. However, the majority of these smart homes and systems use a number of predefined heuristics to detect changes in cognition, which has been demonstrated to focus on the idiosyncratic nuances of the individual subjects, and thus, does not generalize. In this paper, we address this problem by building generalized linear models of home activity of older adults monitored using unobtrusive sensing technologies. We use inhomogenous Poisson processes to model the presence of the recruited older adults within different rooms throughout the day. We employ an information theoretic approach to compare the generalized linear models learned, and we observe significant statistical differences between the cognitively intact and impaired older adults. Using a simple thresholding approach, we were able to detect mild cognitive impairment in older adults with an average area under the ROC curve of 0.716 and an average area under the precision-recall curve of 0.706 using activity models estimated over a time window of 12 weeks. PMID- 26841429 TI - Half-Face Dictionary Integration for Representation-Based Classification. AB - This paper presents a half-face dictionary integration (HFDI) algorithm for representation-based classification. The proposed HFDI algorithm measures residuals between an input signal and the reconstructed one, using both the original and the synthesized dual-column (row) half-face training samples. More specifically, we first generate a set of virtual half-face samples for the purpose of training data augmentation. The aim is to obtain high-fidelity collaborative representation of a test sample. In this half-face integrated dictionary, each original training vector is replaced by an integrated dual column (row) half-face matrix. Second, to reduce the redundancy between the original dictionary and the extended half-face dictionary, we propose an elimination strategy to gain the most robust training atoms. The last contribution of the proposed HFDI method is the use of a competitive fusion method weighting the reconstruction residuals from different dictionaries for robust face classification. Experimental results obtained from the Facial Recognition Technology, Aleix and Robert, Georgia Tech, ORL, and Carnegie Mellon University-pose, illumination and expression data sets demonstrate the effectiveness of the proposed method, especially in the case of the small sample size problem. PMID- 26841430 TI - Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism. AB - It is thought that KRAS oncoproteins are constitutively active because their guanosine triphosphatase (GTPase) activity is disabled. Consequently, drugs targeting the inactive or guanosine 5'-diphosphate-bound conformation are not expected to be effective. We describe a mechanism that enables such drugs to inhibit KRAS(G12C) signaling and cancer cell growth. Inhibition requires intact GTPase activity and occurs because drug-bound KRAS(G12C) is insusceptible to nucleotide exchange factors and thus trapped in its inactive state. Indeed, mutants completely lacking GTPase activity and those promoting exchange reduced the potency of the drug. Suppressing nucleotide exchange activity downstream of various tyrosine kinases enhanced KRAS(G12C) inhibition, whereas its potentiation had the opposite effect. These findings reveal that KRAS(G12C) undergoes nucleotide cycling in cancer cells and provide a basis for developing effective therapies to treat KRAS(G12C)-driven cancers. PMID- 26841431 TI - Electrical switching of an antiferromagnet. AB - Antiferromagnets are hard to control by external magnetic fields because of the alternating directions of magnetic moments on individual atoms and the resulting zero net magnetization. However, relativistic quantum mechanics allows for generating current-induced internal fields whose sign alternates with the periodicity of the antiferromagnetic lattice. Using these fields, which couple strongly to the antiferromagnetic order, we demonstrate room-temperature electrical switching between stable configurations in antiferromagnetic CuMnAs thin-film devices by applied current with magnitudes of order 10(6) ampere per square centimeter. Electrical writing is combined in our solid-state memory with electrical readout and the stored magnetic state is insensitive to and produces no external magnetic field perturbations, which illustrates the unique merits of antiferromagnets for spintronics. PMID- 26841432 TI - Structures of a CRISPR-Cas9 R-loop complex primed for DNA cleavage. AB - Bacterial adaptive immunity and genome engineering involving the CRISPR (clustered regularly interspaced short palindromic repeats)-associated (Cas) protein Cas9 begin with RNA-guided DNA unwinding to form an RNA-DNA hybrid and a displaced DNA strand inside the protein. The role of this R-loop structure in positioning each DNA strand for cleavage by the two Cas9 nuclease domains is unknown. We determine molecular structures of the catalytically active Streptococcus pyogenes Cas9 R-loop that show the displaced DNA strand located near the RuvC nuclease domain active site. These protein-DNA interactions, in turn, position the HNH nuclease domain adjacent to the target DNA strand cleavage site in a conformation essential for concerted DNA cutting. Cas9 bends the DNA helix by 30 degrees , providing the structural distortion needed for R-loop formation. PMID- 26841433 TI - Variability of Stimulant Levels in Nine Sports Supplements Over a 9-Month Period. AB - Many studies have found that some dietary supplement product labels do not accurately reflect the actual ingredients. However, studies have not been performed to determine if ingredients in the same dietary supplement product vary over time. The objective of this study was to assess the consistency of stimulant ingredients in popular sports supplements sold in the United States over a 9 month period. Three samples of nine popular sports supplements were purchased over the 9-month period. The 27 samples were analyzed for caffeine and several other stimulants (including adulterants). The identity and quantity of stimulants were compared with stimulants listed on the label and stimulants found at earlier time points to determine the variability in individual products over the 9-month period. The primary outcome measure was the variability of stimulant amounts in the products examined. Many supplements did not contain the same number and quantity of stimulants at all time points over the 9-month period. Caffeine content varied widely in five of the six caffeinated supplements compared with the initial measurement (-7% to +266%). In addition, the stimulants-synephrine, octopamine, cathine, ephedrine, pseudoephedrine, strychnine, and methylephedrine occurred in variable amounts in eight of the nine products. The significance of these findings is uncertain: the sample size was insufficient to support statistical analysis. In our sample of nine popular sports supplements, the presence and quantity of stimulants varied over a 9-month period. However, future studies are warranted to determine if the variability found is significant and generalizable to other supplements. PMID- 26841434 TI - Intraindividual Variability in Test-Retest Air Displacement Plethysmography Measurements of Body Density for Men and Women. AB - Air displacement plethysmography (ADP) is a popular method for estimating body density (Db). Most ADP tests are performed once, with test-retest investigations scarce. Therefore, we investigated test-retest reliability of ADP. Active men (n = 25) and women (n = 25) volunteered and followed standard pretest guidelines. Participants wore dry, form-fitting swimwear and manufacturer-supplied swim caps. In a single session, two ADP trials with measured thoracic gas volume (TGV) were performed without repositioning participants. Separate 2 (sex) * 2 (ADP trial) repeated-measures ANOVAs were performed to investigate within-between comparisons of Db, TGV, body volume (Vb), and relative fatness (%BF). Paired t tests were used to investigate significant differences as appropriate. The Bland and Altman technique was used to depict individual intertrial variations. For all analyses, alpha =.05. A significant main effect for sex was found; men were lower in %BF and higher in all other variables compared with women. Individual variability was notable (ADP1-ADP2). The range of individual intertrial differences were larger for women than men, respectively, for Db (-0.0096-0.0045 g/cc; -0.0019-0.0054 g/cc), TGV (-0.623-1.325 L; -0.584-0.378 L), Vb (-0.249-2.10 L; -0.234-0.397 L), and %BF (-2.1-4.4%; -0.2-0.9%). When assessing body composition of women via ADP or using Db from ADP in a multicomponent model, at least two trials with measured TGV should be performed and the average of the values recorded and reported. PMID- 26841435 TI - Female Recreational Exercisers at Risk for Low Energy Availability. AB - Low energy availability (LEA) describes the disruption in normal physiological function existent when insufficient energy intake is combined with exercise. To conserve energy a range of endocrine adaptations occur, impairing health and athletic performance. The prevalence of LEA has not been fully established especially among recreational exercisers. Determining recreational exercisers at risk of LEA may help to maximize prevention, early diagnosis and treatment. The design of this study was a cross-sectional online survey. One-hundred and nine female recreational exercisers, with a mean age of 23.8 (SD 6.9) years were recruited via gyms and fitness centers throughout NZ. Participants completed an online questionnaire including questions from the LEAF-Q (Low Energy Availability in Females Questionnaire). A total of 45.0% (CI, 35.4%, 54.8%) of participants were classified as "at risk" of LEA. For every extra hour of exercise per week the odds of being at risk of LEA were 1.13 times greater (CI 1.02, 1.25, p = .016). All participants reporting previous stress fracture injuries (n = 4) were classified as at risk for LEA. Significantly more subjects participating in an individual sport were classified as at risk for LEA (69.6%, CI 24.3%, 54.8%) compared with team sports (34.8%, CI 18.7%, 40.5%) (p = .006). The high prevalence of female recreational exercisers at risk of LEA is of concern, emphasizing the importance of increasing awareness of the issue, and promoting prevention and early detection strategies, so treatment can be implemented before health is severely compromised. PMID- 26841437 TI - The Ventilation-Corrected ParvoMedics TrueOne 2400 Provides a Valid and Reliable Assessment of Resting Metabolic Rate (RMR) in Athletes Compared With the Douglas Bag Method. AB - The aim of the current study was to determine if a single ParvoMedics TrueOne 2400 metabolic cart provides valid and reliable measurement of RMR in comparison with the criterion Douglas Bag method (DB). Ten endurance-trained participants completed duplicate RMR measurements on 2 consecutive days using the ParvoMedics system in exercise mode, with the same expirate analyzed using DB. Typical error (TE) in mean RMR between the systems was 578.9 kJ or 7.5% (p = .01). In comparison with DB, the ParvoMedics system over-estimated RMR by 946.7 +/- 818.6 kJ. The bias between systems resulted from ParvoMedics VE(STPD) values. A regression equation was developed to correct the bias, which reduced the difference to -83.3 +/- 631.9 kJ. TE for the corrected ParvoMedics data were 446.8 kJ or 7.2% (p = .70). On Day 1, intraday reliability in mean RMR for DB was 286.8 kJ or 4.3%, (p = .54) and for ParvoMedicsuncorrected, 359.3 kJ or 4.4%, (p = .35), with closer agreement observed on Day 2. Interday reliability for DB was 455.3 kJ or 6.6% (p = .61) and for ParvoMedicsuncorrected, 390.2 kJ or 6.3% (p = .54). Similar intraday and interday TE was observed between ParvoMedicsuncorrected and ParvoMedicscorrected data. The ParvoMedics TrueOne 2400 provided valid and reliable RMR values compared with DB when the VE(STPD) error was corrected. This will enable widespread monitoring of RMR using the ParvoMedics system in a range of field-based settings when DB is not available. PMID- 26841436 TI - Does Replacing Sodium Excreted in Sweat Attenuate the Health Benefits of Physical Activity? AB - International guidelines suggest limiting sodium intake to 86-100 mmol/day, but average intake exceeds 150 mmol/day. Participants in physical activities are, however, advised to increase sodium intake before, during and after exercise to ensure euhydration, replace sodium lost in sweat, speed rehydration and maintain performance. A similar range of health benefits is attributable to exercise and to reduction in sodium intake, including reductions in blood pressure (BP) and the increase of BP with age, reduced risk of stroke and other cardiovascular diseases, and reduced risk of osteoporosis and dementia. Sweat typically contains 40-60 mmol/L of sodium, leading to approximately 20-90 mmol of sodium lost in one exercise session with sweat rates of 0.5-1.5 L/h. Reductions in sodium intake of 20-90 mmol/day have been associated with substantial health benefits. Homeostatic systems reduce sweat sodium as low as 3-10 mmol/L to prevent excessive sodium loss. "Salty sweaters" may be individuals with high sodium intake who perpetuate their "salty sweat" condition by continual replacement of sodium excreted in sweat. Studies of prolonged high intensity exercise in hot environments suggest that sodium supplementation is not necessary to prevent hyponatremia during exercise lasting up to 6 hr. We examine the novel hypothesis that sodium excreted in sweat during physical activity offsets a significant fraction of excess dietary sodium, and hence may contribute part of the health benefits of exercise. Replacing sodium lost in sweat during exercise may improve physical performance, but may attenuate the long-term health benefits of exercise. PMID- 26841439 TI - Long Superficial Femoral Artery Occlusions: Ready for an Endovascular Intraluminal Approach? PMID- 26841438 TI - Long-Term Outcomes of Self-Expandable Nitinol Stent Implantation With Intraluminal Angioplasty to Treat Chronic Total Occlusion in the Superficial Femoral Artery (TransAtlantic Inter-Society Consensus Type D Lesions). AB - OBJECTIVES: To evaluate the long-term outcomes of self-expandable nitinol stent implantation with intraluminal angioplasty for chronic total occlusion (CTO) in the superficial femoral artery (SFA) of patients with TransAtlantic Inter-Society Consensus (TASC) D lesions. METHODS: From 2004 to 2011, self-expandable nitinol stent implantation in SFA was performed successfully in 72 consecutive limbs of 68 patients with TASC D lesions. These patients were assessed for an average of 38.8 +/- 25.6 months. The procedure was performed using a 0.014" or 0.018" guidewire and intraluminal angioplasty. RESULTS: Patients with hemodialysis constituted 20.6% of cases. The mean occlusion length was 244.6 +/- 34.1 mm. A bidirectional approach was performed in 69.4% of cases. Primary patency rates were 77.9%, 71.9%, 67.2%, and 51.5% at 1 year, 2 years, 3 years, and 5 years, respectively. Secondary patency rates were 88.6%, 78.7%, 71.1%, and 56.0% at 1 year, 2 years, 3 years, and 5 years, respectively. Cox regression multivariate analysis for hemodialysis pertaining to loss of primary and secondary patency resulted in hazard ratio = 2.555 (95% confidence interval, 1.108-5.891; P=.03) for loss of primary patency and hazard ratio = 3.615 (95% confidence interval, 1.380-9.471; P=.01) for loss of secondary patency. CONCLUSION: Long-term patency of self-expandable nitinol intraluminal stent implantation with intraluminal angioplasty to treat CTO (TASC D) in SFA is promising. Hemodialysis was the only independent predictor for loss of primary and secondary patency. PMID- 26841440 TI - Transcatheter Aortic Valve Replacement Complication Rates in Teaching Vs Non Teaching Centers in the United States. AB - OBJECTIVE: The objective of our study is to compare transcatheter aortic valve replacement (TAVR) complication rates among teaching vs non-teaching centers in the United States. METHODS: Using National Inpatient Sample (NIS) data, the largest all-payer database of hospital inpatient stay available in the United States, we identified patients (age >=18 years) who underwent TAVR from January December 2012. We constructed multivariable models to determine independent predictors (age, sex, race, Charlson's comorbidity index, hospital size, hospital location, and TAVR approach) of TAVR-associated complications. RESULTS: We identified 7405 TAVR procedures performed in the United States in 2012. In all, 88% of TAVRs were performed in teaching centers. There was no difference in mortality following TAVR between teaching and non-teaching centers. In-hospital complication rate was lower in teaching centers vs non-teaching centers (42% vs. 50%, respectively; P<.001). In adjusted analysis, hemorrhage requiring transfusion (13.2% vs. 20.8%; P<.001), renal complications requiring dialysis (1.2% vs. 2.3%; P<.01), respiratory complications (7.5% vs. 11%; P<.001), and complications requiring open-heart surgery (2% vs. 4.6%; P<.001) were lower in teaching centers vs non-teaching centers. Vascular access-site, pacemaker insertion, pericardial, and neurological complications were similar between teaching and non-teaching centers. CONCLUSION: Institutional design impacts TAVR complications, albeit with no difference in mortality. In general, complication rates are lower in teaching centers compared with non-teaching centers. PMID- 26841441 TI - How to Build a Better TAVR. PMID- 26841442 TI - A Simple Technique to Facilitate Right Heart Catheter Placement From Right Atrium to Right Ventricle: The Virtual Hydraulic Guidewire Technique. AB - Right heart catheter advancement from right atrium (RA) to right ventricle (RV) is frequently difficult in patients with large and geometrically deformed RAs. We describe a simple technique, using no additional equipment, that significantly improves the probability of successful passage of right heart catheter from RA to RV. PMID- 26841443 TI - Initial Experience With the Gaia Composite Core Guidewires in Coronary Chronic Total Occlusion Crossing. AB - Inability to cross the occlusion with a guidewire is the most common cause of failure of coronary chronic total occlusion (CTO) interventions. We describe two cases of successful application of the novel Gaia family of coronary guidewires (Asahi Intecc) for crossing coronary CTOs using all available crossing strategies, namely antegrade wire escalation, antegrade dissection/reentry, and retrograde. PMID- 26841444 TI - An Amulet to Say "Big is Not Enough". AB - We report the case of a man affected by non-valvular atrial fibrillation in whom a severely enlarged left atrial appendage with a narrow neck was successfully closed with a 34 mm Amplatzer Amulet device (St. Jude Medical). In the presence of a huge appendage with a narrow neck, as in this case, the Amulet should be considered an available option to ensure the feasibility of percutaneous closure. PMID- 26841445 TI - Transcatheter Aortic Valve Replacement: Still in the Way of Learning. PMID- 26841446 TI - Cellular localisation of the kinin B1R in the pancreas of streptozotocin-treated rat and the anti-diabetic effect of the antagonist SSR240612. AB - The mechanism by which kinin B1 receptor (B1R) contributes to type 1 diabetes is addressed by determining the impact of its inhibition on diabetes and on its pancreatic expression and cellular localisation on immunocompetent cells and primary sensory C-fibres. Rats were made diabetic with streptozotocin (STZ). On day 4, they were treated daily for 7 days with a B1R antagonist (SSR240612, 10 mg/kg) or its vehicle. The surviving beta-cells were measured by immunostaining. The expression of B1R, iNOS, TNF-alpha, macrophages, TCD4+, CGRP and TRPV1 was measured by Western blotting, qRT-PCR and immunofluorescence. Macrophages and TCD4+ lymphocytes were absent in control, but distributed abundantly in the pancreas of STZ-diabetic rats. B1R was upregulated on these immune cells infiltrating the diabetic rat pancreas while it was not expressed on primary sensory C-fibres even if the expression of TRPV1 and CGRP was enhanced. SSR240612 prevented the infiltration of macrophages and TCD4+ lymphocytes and the upregulation of B1R, iNOS, TNF-alpha and TRPV1. SSR240612 corrected hyperglycaemia and hypoinsulinaemia by improving the Langerhans islets survival or regeneration. It is concluded that kinin B1R antagonism exerts anti-diabetic action by preventing the infiltration of immune cells in the pancreas and by preserving the integrity of Langerhans islets beta-cells. PMID- 26841447 TI - Highlight: Kinin 2015 at Sao Paulo, Brazil. PMID- 26841449 TI - [Perinatal care and reproductive technique for patients with breast cancer]. PMID- 26841448 TI - Improvement of restless legs syndrome by nabat: a case series and new hypotheses for research. AB - BACKGROUND: Although many hypotheses have been suggested, the pathophysiology of restless legs syndrome (RLS) has not been fully understood. In this case series, we describe eleven cases with RLS whose symptoms subsided by the use of crystallized sucrose. This kind of sugar, known as nabat, is used in traditional Iranian medicine. METHODS: Case series. RESULTS: All patients felt relief 30-60 min after taking 100 grams of dissolved nabat. CONCLUSIONS: Sucrose seems to carry a special benefit for patients with RLS, and it provides evidence for growing literature demonstrating the different underlying mechanisms of RLS. Possible causes for this concurrence are also discussed. PMID- 26841450 TI - [I. Pregnancy-associated breast cancer]. PMID- 26841451 TI - [II. Reproductive issues in women with breast cancer--development of a clinical guide on onco-fertility]. PMID- 26841452 TI - [III. Fertility preservation for breast cancer patients--approach at our institution]. PMID- 26841453 TI - [Lower G.I./colon and rectum cancer]. PMID- 26841454 TI - [Aspirin for the prevention of colorectal cancer]. PMID- 26841455 TI - [Current status of laparoscopic surgery for colorectal cancer]. PMID- 26841456 TI - [Adjuvant chemo/chemoradiation therapy for colorectal cancer]. PMID- 26841457 TI - [Future perspective of immune checkpoint inhibitors in colorectal cancer]. PMID- 26841458 TI - Pediatric cardiology. PMID- 26841459 TI - Respiratory therapists. PMID- 26841460 TI - Pediatric nephrology. PMID- 26841461 TI - The Wound Care Aliance UK (WCAUK) makes the following response to the NHS Supply Chain Generic Project plans. PMID- 26841462 TI - A National Wound Dressings Formulary: what are the issues for patients, practitioners and industry? PMID- 26841463 TI - A National Wound Dressings Formulary: what are the issues for patients, practitioners and industry? PMID- 26841464 TI - A National Wound Dressings Formulary: what are the issues for patients, practitioners and industry? PMID- 26841465 TI - This statement outlines Crawford Healthcare's response to the MA Healthcare (MAH) campaign. PMID- 26841466 TI - Summary of dressing procurement activity by the East Midlands Tissue Viability Group (EMTVG). PMID- 26841467 TI - "Nothing is being done to fix the nursing crisis". PMID- 26841468 TI - Nurses blame fall in staff for workplace pressures. PMID- 26841469 TI - Revalidation: employers must offer nursing staff more support. PMID- 26841470 TI - New associate nurse role backed by most registrants. PMID- 26841471 TI - Council U-turnson health visitor budget cut plan. PMID- 26841473 TI - Nurse prescribers help save NHS almost L1bn a year. PMID- 26841472 TI - Return-to-practice scheme may be extended to care sector. PMID- 26841474 TI - Specialist district nursing role 'vital' to safe community care. PMID- 26841475 TI - Hospital nurses using new rapid influenza test. PMID- 26841476 TI - NICE issues guidance to improve managing IV fluid care in children. PMID- 26841477 TI - Retirement ends 134-year history of family's mental health nursing. PMID- 26841479 TI - "Health service contracts should be won on quality, not on price". PMID- 26841478 TI - "It may not be sensible to fill the vacancies with non-EU labour". PMID- 26841480 TI - "Providing healthcare for the homeless must be a priority". PMID- 26841481 TI - Assessing the health of homeless people. AB - New guidance on assessing the health of homeless people features an assessment template for community nurses working with this group. It includes key questions on general physical health, mental health, long-term conditions, substance use, sexual health and housing. It also incorporates template care plans for use by both nurses and patients, and includes Read Codes for practice-based settings. This article looks at the impact homelessness can have on health, and summarises the Queen's Nursing Institute's guidance on assessing the healthcare needs of homeless people. PMID- 26841482 TI - Revalidation: Dispelling the myths. PMID- 26841483 TI - Treatment of obesity hypoventilation syndrome. AB - Aside from being a health concern in itself, obesity can result in other serious health conditions. Some of these, such as cancer, can result in early death, while others, including sleep-disordered respiratory problems, can compromise patients' day-to-day quality of life and economic status. This article explores how obesity affects respiratory disorders and focuses on obesity hypoventilation syndrome. It outlines the pathophysiology and diagnosis of the condition, and explains how it can be treated with non-invasive ventilation. PMID- 26841484 TI - How to address wound healing complications. AB - The final article in this six-part series looks at wound complications. While most acute wounds will heal with the right treatment, some get stuck along the normal healing pathway and become chronic. The pathology of these wounds is complex, requiring nurses to determine and eliminate any underlying problems, such as poor circulation, while preventing colonisation to avoid infection. Through appropriate treatment and the correct dressing choice, nurses can help prevent a chronic wound from getting worse and put it back on the path to healing. Some wounds will never be able to heal; in such cases, nurses can help to relieve patient discomfort. PMID- 26841485 TI - 60 SECONDS WITH Vicki Abrahams. PMID- 26841486 TI - Minding all the gaps. PMID- 26841487 TI - Meeting the needs of patients and staff. PMID- 26841488 TI - [PLANT GENETIC TRANSFORMATION USING CARBON NANOTUBES FOR DNA DELIVERY]. AB - The possibility of exploiting carbon nanotubes (CNTs)-based nanocarriers to deliver genes into protoplasts, callus and mesophyll explants of plants was examined. Using single-walled CNTs (SWCNTs) at the concentration of 20 MUg/ml and multi-walled CNTs (MWCNTs) at the concentration of 15 MUg/ml genetic transformation of Nicotiana tabacum L. mesophyll protoplasts with plasmid pGreen 0029 was carried out and transient expression of reporter yfp gene in the protoplasts was observed. Using SWCNTs at the concentration of 40 MUg/ml and MWCNTs at the concentration of 30 MUg/ml genetic transformation of N. tabacum callus and leaf explants with nptII gene as a part of plasmid pGreen 0029 was carried out. As a result plant regeneration on selective medium containing 50 mg/lkanamycin was shown. SWCNTs-based nanocarriers de-onstrated their appli ability to transform protoplasts as well as walled plant cells. Whereas, MWCNTs based nano-arriers were suitable only for transformation of proto-lasts due to the limiting role of cellulose walls in cell penetration. PMID- 26841489 TI - [THE EFFECT OF waaL LIGASE GENES DELETION ON MOTILITY AND STRESS ADAPTATION REACTIONS OF YERSINIA ENTEROCOLITICA 6471/76]. AB - The aim of current study was to estimate the influence of waaL(OS) and waaL(PS) genes deletion on lipopolysaccharide (LPS) synthesis, bacterial motility and stress resistance of bacteria Yersinia enterocolitica 6471/76. Single and double waaL mutants were created by replacing the wild-type alleles in bacterial chromosome for mutant ones. The phenotypes of mutants were visualized by DOC-PAGE gels stained with silver and immunoblot with specific to O-polysaccharide and outer core monoclonal antibodies. Bacterial motility was evaluated by the diameter of the migration zone. Wild type bacteria and mutants were analyzed by bacterial growth curves in a hypertonic medium. Participation of WaaL ligases in resistance to osmotic pressure was found only in case of both ligese genes deletion. Also the YeO3_os_ps mutants showed motility decreasing, which recovered after adding a functionally active gene. Thus, deletion of both waaL ligase genes lead to a drastic reduction in bacterial motility and increase their sensitivity to hypertonic medium that can indirectly characterize biological role of WaaL ligases. PMID- 26841490 TI - [POLYMORPHISM OF ALFA-AMYLASE AND CONJUGATION IN COMMON WHEAT ENZYME TYPES WITH QUANTITATIVE TRAITS OF PLANTS]. AB - Using polymorphism of alpha-amylase in the winter common wheat studied inheritance isoenzymes and its conjugation enzyme types with germinating grain on the "vine", grain productivity, plant height and time of ear formation. It is shown that the polymorphism isoenzyme of alpha-amylase wheat is limited by the presence of different loci whose products are similar in electrophoretic parameters. In this regard, one component of the enzyme can be controlling at one or two or three genes. Identification of a locus controlling alpha-amylase isoenzyme in the fast moving part of the electrophoretogram, designated as alpha Amy-B7. Determine the distance of the locus to factor alpha-Amy-B6. PMID- 26841491 TI - [MspI-POLYMORPHISM IN FOURTH INTRON OF THE GROWTH HORMONE GENE IN CHICKEN POPULATIONS OF DIFFERENT BREEDS. ANALYSIS OF THE CAUSES OF ADDITIONAL RESTRICTION PATTERN ORIGIN]. AB - The MspI-polymorphism in the fourth intron of the growth hormone gene in populations of White Plymouth Rock, Poltava Clay, Rhode Island Red and Borkovskaya Barvistaya chicken breeds was studied. It is shown that in all examined chicken populations the growth hormone gene is polymorphic. It was found that the presence of "additional" phenotype (restriction pattern) is not associated with duplication of the growth hormone gene. The possibility of formation of heteroduplex DNA of two different types in the course of amplification of heterozygous samples B/C, containing the site 'CCGG', which leads to formation the additional DNA fragment which do not contain the site 'CCGG', was described. The nucleotide sequences of alleles A, B, C and "additional" fragment is described. Frequencies of alleles A, B and C in chicken population of White Plymouth Rock breed were 0.56; 0.16 and 0.28; Poltava Clay- 0.10; 0.07 and 0.83; Rhode Island Red--0.27; 0.31 and 0.42; Borkovskaya Barvistaya--0.75; 0.08 and 0.17 respectively. PMID- 26841492 TI - PRODUCTION OF A NOVEL ROBERTSONIAN TRANSLOCATION FROM THINOPYRUM BESSARABICUM INTO BREAD WHEAT. AB - Development of wheat-alien translocation lines will facilitate its practical utilization in wheat improvement. The objective of the present study was to produce compensating wheat--Thinopyrum bessarabicum whole arm Robertsonian translocations (RobTs) involving chromosomes 2B of wheat and 2E(b) of Th. bessarabicum through the mechanism of centric breakage-fusion. F2 population from crosses between DS2E(b)(2B) substitution line and bread wheat 'Roushan' (2n = 6x = 42, AABBDD) as female parent were made. Forty one F2 lines (L1 to L41) were screened for their chromosome composition. Three 2E(b) specific PCR-based Landmark Unique Gene (PLUG) markers were used for screening F2 progeny derived from plants double-monosomic for chromosome 2B and 2E(b). Two Rob Ts (-5%) were observed among F2 plants. Homozygous translocation (T2E(b)S.2BL) with good plant vigor and full fertility were selected from F3 families. The T2E(b)S.2BL stock has longer awn than that of its parents. It is cytogenetically stable, and may be useful in wheat improvement. PMID- 26841493 TI - CYTOTOXIC EFFECTS OF METAPHASE-ARRESTING METHODS IN BARLEY. AB - Metaphase-arresting agents amiprophos-methyl (APM), colchicine (COL) and cell cycle-synchronization (CCS) with APM and hydroxyurea (HU) were tested for growth, metaphase index and cytogenetic abnomalities in barley (Hordeum vulgare cv. Bornova-92). Seeds were germinated for 2 days and then seedlings were treated with 8 MUM (2.4 mg/l) APM for 2 h or 1.25 mM (0.5 g/l) COL or synchronized (CCS) with 1.25 mM (95 mg/l) hydroxyurea for 18 h and with 4 MUM (1.2 mg/l) APM for 2 h. APM and CCS caused metaphase indices 12.57 and 38.82% respectively. COL also arrested metaphase (14.10%) but also resulted in nuclear aberrations (11.15%). After removal of APM and CCS, cells were released to grow and divide. However, COL caused irreversible effects on cell division and growth and meanwhile was shown to be effective for micronucleus formation. PMID- 26841494 TI - CYTOGENETICAL TREATISE OF INDIAN REPRESENTATIVE SPECIES OF CUCUMIS. A KARYOTYPIC APPROACH. AB - Karyomorphological studies have been carried out in nine species and five varieties of the genus Cucumis representing Indian gene pool. The present investigations reveal the occurrence of two somatic chromosome numbers 2n = 14, 24 in the genus. C. ritchiei and C. indicus the two new species, were found to be having somatic chromosome numbers of 2n = 24 and 2n = 20 respectively. The wild species viz. C. hystrix, C. setosus, C. prophetarum, C. dipsaceus, C. indicus have very less number of median-centromeric chromosomes, high asymmetry indices, while melon groups have intermediate number of median -centromeric chromosomes. C. sativus, C. callosus, C. ritchiei show lesser number median-cen-tromeric chromosomes and very less asymmetry indices. The importance of karyotypic variation with respect to speciation within the genus Cucumis have been discussed. PMID- 26841495 TI - [DEVELOPMENT OF MARKER-FREE TRANSFORMANTS BY SITE-SPECIFIC RECOMBINASES]. AB - To produce transgenic plants in current biotechnology selectable marker genes are used that lead to the selectivity.of transformants from non-transformed organisms. However, after the transgenic event has been occurred, the presence of these genes in transformed genome in general is uselless. Moreover, the continued presence of this kind of genes in transgenic plants with their further commercialization may raise certain public concern. Therefore, various techniques have been developed in recent years to obtain marker free transgenic plants. In the present review the main strategies for removal of selective marker DNA sequences that are used in genetic engineering are described. The most popular among them is site-specific recombination technology. The particular attention is paid to site-specific recombinase system Cre/loxP. The using of a new approach with site-specific recombinase system Cre/loxP under the control of 35S promoter to generate marker-free genetically modified plants is described. PMID- 26841496 TI - FROM Qutn TO Bt COTTON: DEVELOPMENT, ADOPTION AND PROSPECTS. A REVIEW. AB - Cotton has unique history of domestication, diversification, and utilization. Globally it is an important cash crop that provides raw material for textile industry. The story of cotton started from human civilization and the climax arrived with the efforts of developing transgenic cotton for various traits. Though conventional breeding brought steady improvement in developing resistance against biotic stresses but recent success story of gene transferfrom Bacillus thuringiensis into cotton showed game changing effects on cotton cultivation. Amongst various families of insecticidal proteins Bt Cry-toxins received more attention because of specificity against receptors on the cell membranes of insect midgut epithelial cells. Rapid Bt cotton adoption by farmers due to its economic and environmental benefits has changed the landscape of cotton cultivation in many countries. But the variable expression of Bt transgene in the newly developed Bt cotton genotypes in tropical environment is questionable. Variability of toxin level in different plant parts at various life stage of plant is an outcome of genotypic interaction with environmental factors. Temporal gene expression of Cry1Ac is also blamed for the epigenetic background in which transgene has been inserted. The presence of genotypes with sub-lethal level of Bt toxin might create resistance in Lepidopteron insects, limiting the use of Bt cotton in future, with the opportunityfor other resistance development strategies to get more attention like gene stacking. Until the farmers get access to more recent technology, best option is to delay the development of resistance by applying Insect Resistance Management (IRM) strategies. PMID- 26841497 TI - [Investigation of the Dependence of Escherichia coli RNA Polymerase sigma70 Subunit Structure on Ionic Strength by Molecular Dynamics Simulation Method]. AB - The sigma70-subunit of E. coli RNA polymerase (a small protein, being a part of RNA holoenzyme, and responsible for initiation of transcription of constitutive genes) is modeled at different ionic strengths. Two variants of the location of C end domain 4 are obtained. At low ionic strength domain 4 interacts with the region of high negative charge 190-210 AK within NCR domain. At high ionic strength this region was screened and domain 4 was free and set away from domain NCR. We suppose that this leads to the increase in polymerization rate. Simulation data do not confirm any hypothesis about a self-inhibition mechanism. PMID- 26841498 TI - [Developing the Mathematical Method in order to Search for Latent Periodicity in Protein Amino Acid Sequences with Deletions and Insertions]. AB - A mathematical method was developed in order to search for latent periodicity in protein amino acid and other symbolical sequences using the dynamic programming and random matrixes. The method permits detection of the latent periodicity with insertions and deletions in the previously unknown positions. The developed method was applied to search for the periodicity in the amino acid sequences of some proteins and the periodicity in EUR/USD exchange rate since 2001. The presence of the long period length with insertions and deletions in amino acid sequences was shown. The period length of 7 amino acids was found in proteins containing supercoiled areas (coiled coil), the period length of 6 and 5 and more amino acids was also demonstrated. The existence of the period length of 6 and 7 days as well as 24 and 25 hours in the analyzed financial time series, which can be detected with insertions and deletions only, is revealed. The reasons of the occurence of the latent periodicity with insertions and deletions in the amino acid sequences and financial time series are discussed. PMID- 26841499 TI - [Prediction of Protein Conformational Mobility and Evaluation of Its Reliability Using Small-Angle X-ray Scattering]. AB - The "coarse-grained" model of protein conformational mobility is presented. We compared the trajectories of conformational motions predicted for five proteins using this model with the motion obtained by the method of the "nearest neighbor", based on small-angle X-ray scattering data. It is shown that for all studied proteins the sequence of conformations calculated on the basis of "coarse grained" model and on the basis of the "nearest neighbor", coincides well, although there are exceptions. Some separate consideration should be given to each protein to discern the causes of these exceptions. PMID- 26841500 TI - [Assessment of Binding Properties of Actinomycin and Its Derivatives with DNA Molecule Using Molecular Dynamics Simulation Method]. AB - Molecular dynamics simulation method was used to assess an influence of actinomycins (antibiotics used in chemotherapy for treatment of some oncology diseases) on DNA fragment elasticity. Also the efficiency of binding of actinomycin to DNA fragment was estimated. Energetic contributions of different substitutions of hydroxyl and amino-group to the phenoxazine ring of actinomycin were studied to analyze dynamic behavior and stability of antibiotic-DNA fragment complexes. Young modulus values were calculated for structures: DNA/DNA actinomycin/DNA-7-hydroxyactinomycin/DNA-7-aminoactinomycin. Free energy calculations were performed for the formation of actinomycin- and two actinomycin analogues-DNA fragment complexes. Our results suggest that the inserted substitutions stabilize the structure of a DNA fragment via the formation of additional hydrogen bonds. PMID- 26841501 TI - [Comparative Efficiency of Algorithms Based on Support Vector Machines for Regression]. AB - Methods of construction of support vector machines do not require additional a priori information and can be used to process large scale data set. It is especially important for various problems in computational biology. The main set of algorithms of support vector machines for regression is presented. The comparative efficiency of a number of support-vector-algorithms for regression is investigated. A thorough analysis of the study results found the most efficient support vector algorithms for regression. The description of the presented algorithms, sufficient for their practical implementation is given. PMID- 26841502 TI - [Influence of Low-Frequency Electromagnetic Field on DNA Molecules in Water Solutions]. AB - It is shown that the amplicons of hepatitis virus DNA (hepatitis B virus, hepatitis C virus) are capable of inducing radiation after an exposure to electromagnetic fields in the frequency range from 3 to 30 Hz and the field strength, 24-40 A/m, registered by means of a chemiluminescence method. The most effect of the electromagnetic field on water solutions of the amplicons of hepatitis virus DNA occurs at the frequency of 9 Hz, the change in the hydration shell of DNA amplicons is observed. It is suggested that the change in the hydration shell of DNA amplicons exposed to the low-frequency electromagnetic field leads to restoration of hydrogen bonding, stitchings formation and DNA repair as a whole. PMID- 26841503 TI - [Effects of Light Near-Infrared Radiation on Rats Assessed by Succinate Dehydrogenase Activity in Lymphocytes on Blood Smears]. AB - Biological effects of light near infrared radiation (850 nm), with modulation acoustic frequency of 101 Hz, was studied. The study was conducted on rats, the effect was recorded by succinate dehydrogenase activity in lymphocytes on the blood smear after administration of the activating dose of adrenaline, which simulates the state of the organism in the early stages of the pathogenic effects (stress). A pronounced regulating effect of infrared radiation on the activity of succinate dehydrogenase in animals activated by adrenaline was shown. Infrared radiation has a normalizing effect reducing the degree of inhibition or activation of the enzyme induced by adrenaline and had no effect on the control animals. Thus, by modulating the activity of succinate dehydrogenase infrared radiation regulates energy production in the mitochondria supported by the most powerful oxidation substrate--succinic acid, which is especially pronounced under stress. PMID- 26841504 TI - [Protomitohondria of Liver Cells, Their Similarities and Differences between Mitochondria]. AB - In this paper we continue the study of a number of properties of protomitochondria--small young mitochondrial organelles in the animal cells. Protomitochondria were obtained by filtration of total suspension of mitochondria of rat liver through Millipore filters. Protomitochondria contain an active respiratory chain as evidenced by the high rate of oxygen consumption during succinate and NADH oxidation. A shunt succinate:tetrazolium-reductase activity of protomitochondria was lower and NADH-tetrazolium-reductase activity was higher than that in mitochondria. Electrophoresis and gel filtration found no qualitative differences between protomitochondria, 0.25-0.45 MUm in diameter, and mitochondria in major protein composition, but some quantitative differences in several bands were found. Perhaps, these differences reflect the process of intracellular maturation of protomitochondria to mitochondria. The data obtained are important for understanding the mitochondriogenesis in the animal cells. PMID- 26841505 TI - [Influence of Microbial Metabolites of Phenolic Nature on the Activity of Mitochondrial Enzymes]. AB - The aim of this work was to study the effect of microbial metabolites of phenolic nature on the activity of enzymes of the tricarboxylic acid cycle in isolated mitochondria, and determine metabolites of the tricarboxylic acid cycle as potential biomarkers of mitochondrial dysfunction in the blood of patients with sepsis. It is shown that microbial metabolites of phenolic nature have an inhibitory effect on the activity of dehydrogenases, determined by the reduction of dichlorophenolindophenol and nitroblue tetrazolium in liver mitochondria and liver homogenates. This effect is more pronounced in oxidation of the NAD dependent substrates than succinate oxidation, and at lower concentrations of microbial metabolites than inhibition of respiration. By gas chromatography-mass spectrometry it was found that the content of the tricarboxylic acid cycle metabolites in the blood of patients with sepsis decreased compared to healthy donors. The data obtained show that the microbial phenolic acids can contribute significantly to the dysfunction of mitochondria and suppression of general metabolism, characteristic of these pathologies. PMID- 26841507 TI - [Biophysical Model of Contractile Activity of Muscle Cells]. AB - Muscle cells have the specific structure, the advanced cytoskeleton, which takes most of cell volume and forms a contractile apparatus. On the basis of the equations of continuum mechanics we proposed a mathematical model of the biomechanical behavior of cells as a whole, and it was modified to describe the contractile activity in muscle cells as an elastic rod. The model takes into account the result of transduction of external influences, namely the development of internal deformation, and allows for estimation of mobility and/or tension developed in muscle cells in the case of change in external influence. PMID- 26841506 TI - [Degradation of Mitochondria to Lipofuscin upon Heating and Illumination]. AB - In the present work, it has been shown that the isolated mitochondria can undergo transformation to lipofuscin granules without any additional factors (oxygen saturation, prooxidants). The process occurs spontaneously and slowly at low temperature, and rapidly--by heating (thermo-lipofuscin) or under UV irradiation (photo-lipofuscin). The main contribution to the formation of mitochondrial lipofuscin comes from denatured proteins. Thermo-formation of lipofuscin depends on lipid peroxidation, while the presence of lipids is not required for photo lipofuscin formation. It is shown that the use of detergent able to degrade mitochondria is necessary to measure lipofuscin content properly. PMID- 26841508 TI - [Interaction of Membrane and Calcium Oscillators in Cardiac Pacemaker Cells: Mathematical Modeling]. AB - An integrative model of the calcium dynamics in cardiac pacemaker cells is developed taking into account a synergetic effect of the interaction between an outer membrane oscillator and an intracellular calcium oscillator ("membrane and Ca(2+)-clock"). The main feature of the model is a description of the stochastic dynamics of Ca2+ release units within the electron-conformational mechanism of the functioning of ryanodine-sensitive calcium channels. It is shown that interaction of two cellular oscillators provides a stable action potential generation in the cardiac pacemaker cells even in the case of the stochastic Ca2+ dynamics. We studied in detail the effect of ryanodine channels sensitivity to an increase in the intracellular calcium concentration in sarcoplasmic reticulum and in the dyadic space on the behavior of calcium-release system. A parametric analysis of the integrative model of pacemaker cells is performed. PMID- 26841509 TI - [Inhibition of NF-kB Activation Decreases Resistance in Acute Myeloid Leukemia Cells to TRAIL-induced Apoptosis in Multicellular Aggregates]. AB - Suppression of resistance in acute myeloid leukemia cells to TRAIL-induced apoptosis in multicellular aggregates, was studied using small molecule inhibitors of the activation of the transcription factor NF-kB - NF-k9 Activation Inhibitor IV and JSH-23 at non-toxic concentrations. NF-kB Activation Inhibitor IV and JSH-23 reduced resistance in the acute myeloid leukemia cells in multicellular aggregates to cytotoxic action of recombinant protein izTRAIL. It is shown that the use of these inhibitors decreased the phosphorylation of the RelA (p65) as a main marker activation of the transcription factor NF-kB. We discuss a possible reason for increasing resistance in acute myeloid leukemia cells to TRAIL-induced apoptosis in multicellular aggregates. PMID- 26841510 TI - [Cytoprotective Effects of Phytoestrogen Genistein against Cancer Cells]. AB - In this paper we study the effect of synthetic isoflavonoid genistein against cancer HeLa cells, which contain estrogen receptors alpha but not beta, with the aim to determine the cytotoxic or cytoprotective effect of genistein. It is shown that the half maximal inhibitory concentration (IC50) value of genistein (0.2 mM) for the growth inhibition of HeLa cells is at least ten times higher than that one of tamoxifen and cisplatin--drugs, used in cervical cancer treatment. In micromolar concentrations (0.1-10 MUM) genistein decreased the cytotoxic effects of cisplatin and tamoxifen. The decreased Bax mRNA expression and increased Bcl-2 mRNA expression after incubation .of the cells with genistein also demonstrate the cytoprotective, anti-apoptotic effect of genistein. Genistein, even in high concentrations, had no effect on membrane potential and calcium capacity of isolated mitochondria, without activating the opening of Ca(2+)-induced mitochondrial pore. Thus, these data demonstrate a cytoprotective effect of isoflavonoid genistein against this type of cancer cells. PMID- 26841511 TI - [Anti-Tumour Activity of Dinitrosyl Iron Complex with Glutathione and S Nitrosoglutathione Preparations: Comparative Studies]. AB - The anti-tumor activity of the binuclear form of dinitrosyl iron complexes with glutathione against Lewis lung carcinoma, found earlier upon intraperitoneal administration of the complexes, was also observed when this preparation was injected subcutaneously. A 100 MUM/kg subcutaneous dose of the complex being used daily (as calculated per one iron atom in binuclear dinitrosyl iron complexes) for 10 or 15 days, inhibited the tumor growth by 43%. The effect was observed during the first two weeks after tumor transplantation. After that, the tumors began to grow at the rate equal to or even higher than that one for control animals. The mean survival time for treated mice exceeded the control values by 30%. Binuclear dinitrosyl iron complexes administered intraperitoneally was also effective against Ca-755 adenocarcinoma. However, in this case the mean survival time for treated animals increased only by 7%. The anti-tumor activity of S nitrosoglutathione against Lewis lung carcinoma growth inhibition by 70% and Ca 755 adenocarcinoma growth inhibition by 90% was also shown. However, unlike binuclear dinitrosyl iron complexes the anti-tumor effect of S-nitrosoglutathione decreased when a daily dose of the compound increased (from 200 to 400 MUM/kg) The initial anti-tumor effect of binuclear dinitrosyl iron complexes and S nitrosoglutathione is suggested to be due to NO released from both compounds. A subsequent suppression of the effect is determined by the development of anti nitrosative and anti-oxidant defense systems in tumors. PMID- 26841512 TI - [Effect of Hepatic P450 2e1 Activity Modulation on the Toxicity and Carcinogenicity of Diethylnitrosamine in Mice]. AB - In this paper, the biological effects of diethylnitrosamine have been studied under controlled conditions of its metabolism in mice of different ages. The data presented indicate that diethylnitrosamine in a non-metabolized form exerts general toxic and hepatocarcinogenic effects while alkylating agents of this compound produce toxic liver injury. To our knowledge, the data presented impel to revise the general notion of an exceptional role of mutagenic activation in the carcinogenic effect of chemicals. PMID- 26841513 TI - [Mathematical Modeling of the Stretching-induced Elongation of an Embryonic Epithelium Layer in the Absence of External Load]. AB - A clue to understanding the deformation of a plane embryonic epithelium layer unloaded after a short time uniaxial stretch and fixation in a stretched state over different time periods is found. The first steps in the understanding of this process come from the knowledge about the uniform stretching of the tissue fragment (explantate) with the subsequent stretching at a fixed length. In this study we used the earlier developed continuum model that describes the stress strain state of the epithelial tissue taking into account the parameters that characterize the shape of the cells and their stress state, and also the active stresses they exert when interact with one another. The experimentally observed continuation of deformation of the stretched tissue after the cessation of action of the external force is described theoretically as a result of active cell reactions to the mechanical stress. The strong effect of the duration of explantate fixation on its further elongation and the cell activity pattern is demonstrated. PMID- 26841514 TI - [Mathematical Modelling of the Dependence of the Performance of the Left Ventricle of the Heart on Preload and Afterload]. AB - The results of the numerical simulation of the end-diastolic, end-systolic and stroke volumes of the left ventricle of the heart are presented. The simulation was based on a published simple kinetic model of cardiac muscle and approximation of the ventricle geometry with thick-wall cylinder where the fibre orientation varied linearly from sub-epicardium towards sub-endocardium. Blood flow was modelled with a liner compartment model. This simplified approach provides correct dependencies of the stroke volume on the pre- and afterload, namely end diastolic pressure and peripheral resistance. The calculations show that the stroke volume is independent of arterial compliance and blood inertia. PMID- 26841515 TI - [Studying the Persistence of Blood Flow Oscillations in Rat Kidneys]. AB - This work was designed to study the nonlinear dynamics of fluctuations in renal blood flow of rats under basal conditions and in the perturbed state. An intramuscular injection of aspirin in 0.9% physiological saline (0.5 mg per 100 g body weight) served as a perturbation factor. Capillary blood flow in the right kidney of a rat was measured by the method of laser Doppler flowmetry. The persistence of these time series was estimated by the Hurst method. Our study revealed the persistence of time series under basal conditions (Hurst index H = 0.817 +/- 0.041). Statistical parameters of the perturbed series were shown to differ significantly from those observed in the initial state. However, the perturbed series remained persistent. The Hurst index for these series was H = 0.677 +/- 0.057. A decrease in this index was insignificant (as compared to that for the baseline index). PMID- 26841516 TI - [On Two Opposing (Bio)surfaces as Comprehended in Terms of an Extension of the Coulomb-Amontons Law of Friction, with Its Virtual Usefulness for Biotribology in Nanoscale]. AB - An extension of the Coulomb-Amontons law is proposed in terms of an interaction detail involving renormalization (simplified) n-th level scheme. The coefficient of friction is obtained in a general exponential (nonlinear) form, characteristic of virtually infinite (or, many body) level of the interaction map. Yet, its application for a hydration repulsion bilayered system, prone to facilitated lubrication, is taken as linearly confined, albeit with an inclusion of a decisive repelling force/pressure factor. Some perspectives toward related systems, fairly outside biotribological issues, have been also addressed. PMID- 26841517 TI - [Methods for Reducing Laser Speckles to Achieve Even Illumination of the Microscope Field of View in Biophysical Studies]. AB - The aim of this work was to compare different speckle reduction techniques. It was shown that the use of devices based on liquid crystals only leads to partial reduction of speckle contrast. In quantitative luminescent microscopy an application of the mechanical devices when a laser beam is spread within the field of view turned out to be more efficient. Laser speckle noise was virtually eliminated with the developed and manufactured mechanical device comprising a fiber optic ring light guide and the vibrator that permits movement of optical fiber ends towards the laser diode during measurements. The method developed for the analysis of microarrays was successfully applied to the problem of speckle reduction. PMID- 26841518 TI - [Search for the Influence Contributing to the Study of an Underlying Cause of Water Cluster Structure]. AB - One of the theoretical underlying causes of the formation of water cluster structure is based on nuclear ortho/para spin isomerism of H2O molecules. This theory was so convincing that motivated the search for the experiments on theory validation. The long-term increase in the number of models of the supramolecular water structure did not lead to a reliable result yet, despite numerous efforts of large research teams. It is shown experimentally that the theory of nuclear ortho/para isomers can be validated with a high degree of reliability. It is revealed that a supramolecular model of water cluster structure in a metastable state forms a center of crystallization at the positive electrode using oxygen associates. PMID- 26841519 TI - [Period-tripling in Multiscale Physical and Biological Events]. AB - A recent paper by S.J. Puetz et al. (Chaos, Solitons -& Fractals, v. 62-63, p. 55, 2014) described a fundamental period-tripled model. It involves periods of different astronomical (quasars, Sun), geophysical (geomagnetic, climatic, volcanic) and some biological processes. This work contains statistics for sixteen pairs of a period-tripled sequence. These periods range from -50 years to 1.5 billion years and no signs of the timescale limitations are found. We believe that the universal scope of the fundamental period-tripled model can be used for the development of new methodology of research data analysis: the main idea is that the spectrum of the periods of the studied event should be tested for the similarity with the spectrum of fundamental period-tripling pattern (because of the fundamental nature of the period-tripled model). Using this method, in this study we complement an already described period-tripled model with periods of human memory performance ranging from one minute to one month also adding seven relevant periods/frequencies of the period-tripled model in the range of human hearing. We make a conclusion that these characteristic frequencies may form the basis for music and singing phenomena. The new methodology is particularly appropriate for being applied in medicine and engineering. PMID- 26841520 TI - [The Effect of the Chromophore Charge on the Efficiency of Incorporation of Fluorescently-labeled Nucleotides in Matrix Synthesis by Taq DNA Polymerase]. AB - In order to study the effect of an electrical charge of the chromophore, on the efficiency of incorporation of fluorescently-labeled nucleotides into DNA during PCR, three fluorescently-labeled dUPT, one of which with electroneutral and other two with positively and negatively charged dyes (Cy5 analogs), were synthesized. It is shown that dUPT, labeled with electroneutral Cy 5 analog, is most effectively incorporated into DNA when Tag polymerase is used for PCR. PMID- 26841521 TI - [Method of Entirely Parallel Differential Evolution for Model Adaptation in Systems Biology]. AB - We developed a method of entirely parallel differential evolution for identification of unknown parameters of mathematical models by minimization of the objective function that describes the discrepancy of the model solution and the experimental data. The method is implemented in the free and open source software available on the Internet. The method demonstrated a good performance comparable to the top three methods from CEC-2014 and was successfully applied to several biological problems. PMID- 26841522 TI - [Analysis of the cerebral mechanisms underlying rehabilitation of the patients after stroke]. AB - The authors present the results of the comprehensive analysis of the principal cerebral mechanisms involved in the processes of rehabilitation of the patients after stroke based on the review of the literature concerning this issue. The data obtained in the course of original investigations including 203 patients who had undergone stroke confirm and refine the currently available information pertinent to the problem in question. First and foremost, they demonstrate the influence of the demographic, neurophysiological, and clinical factors as well as neuroimaging and ultrasound studies on the parameters of the evoked potentials in the brain of the stroke-affected patients. In addition, they provide a deeper insight into the role of short-term memory in the realization of the motor response. The probable macro- and microstructural, functional, neurochemical, and pathophysiological mechanisms contributing to the rehabilitation of the patients who had undergone stroke are considered with reference to their relationships. Special emphasis is laid on the methods for regulation of these mechanisms. PMID- 26841523 TI - [The modern approaches to the prognostication of rehabilitation of the patients after stroke on an individual basis: a review of the literature and the results of original investigations]. AB - This article was designed to analyze the results of the investigations with the purpose of elucidation of the prognostic factors relevant to the rehabilitation of the patients who survived after stroke. Special attention is given to the role of demographic (age and sex) factors and the data of the clinical, neurological, psychological, cognitive, and instrumental examination of the patients. The results of the original studies based on the treatment of 203 stroke patients are discussed in the context of modern concepts of the significance of the factors contributing to the recovery of the patients in the course of the post-stroke rehabilitation. The prognostic value of the selected factors, such as leukoareosis (for the patients presenting with hemorrhagic stroke), has been demonstrated for the first time. The new data on the duration of the rehabilitation period are presented with reference to its dependence on the type of stroke and localization of the lesions. Specifically, it is estimated to be 2 years for the patients who suffered from ischemic stroke in the brain stem, 31 months for those with ischemic stroke of the hemispherical localization, and 38 months for the patients presenting with hemorrhagic stroke (hemispherical hematoma). In addition, the data on the magnitude of the post-ischemic atrophic changes of prognostic values are presented. PMID- 26841524 TI - [The role of physiobalneotherapy in the prevention of weather-dependent exacerbations in the patients presenting with chronic obstructive pulmonary disease]. AB - The present publication presents the available data concerning the mechanisms of the development of enhanced meteosensitivity in the patients presenting with chronic broncho-obstructive pulmonary pathology with special reference to the characteristics of the most important biotropic weather factors acting on the population of the Moscow region. The possibility is substantiated for the introduction of non-medicamental methods (such as gas-air sodium dioxide bathtubs, whole body bathtubs with the use of mitofen preparations, and interval hypoxic trainings) into the prophylactic programs designed to prevent weather dependent exacerbations of the chronic obstructive pulmonary disease. PMID- 26841525 TI - [The effectiveness of gait rehabilitation in the patients following endoprosthetic hip replacement by means of the biofeedback-based hardware videoreconstruction of the walking stereotype]. AB - The number of surgical interventions performed for total arthroplasty of the lower extremities (TALE) grows steadily which accounts for the increasingly greater number of patients in need of high-quality and efficient rehabilitation therapy during the post-operative period. In connection with this, the evaluation and implementation of the novel rehabilitation techniques for the management of the patients after TALE is a highly topical problem. We have studied the influence of the method of the biofeedback-based hardware videoreconstruction of the walking stereotype (BOSVRH) in the patients who had undergone total hip arthroplasty during the early postoperative period. The study included three groups of patients. Those of group I (n = 65) were chosen for the training on a treadmill with BOSVRH. In group II (n = 50), the restoration of the walking stereotype was a component of exercise therapy without the use of special hardware techniques. The patients of group III (n = 40) were healthy subjects with no clinical signs of arthrosis in the medical history who served as controls. The analysis of the test results in the end of the training course for the restoration of the walking stereotype in the patients of groups I and II in comparison with the "standard" values in the patients of control group III has demonstrated a more efficient restoration of the waling stereotype in the patients of group I than in those of group II. In the former group, the analysis of the results of dynamic observation of the features of the constituent step elements revealed the improvement of their structural characteristics, the normalization of the symmetry of the load distribution between the lower extremities during walking, and the restoration of the amortization function of the operated limb. In addition, the patients of group I showed a markedly increased level of motivation and satisfaction with the treatment. The control X ray examination of the implanted joints during the long term follow-up period did not reveal any case of displacement of the prosthetic components. It is concluded that the restoration of the walking stereotype in the patients following hip endoprosthetic hip replacement by means of the biofeedback-based hardware videoreconstruction of the walking stereotype during the early postoperative period is an efficient and safe method of the rehabilitative treatment. PMID- 26841526 TI - [Dynamics of the cognitive function in the school-age children presenting with a natal injury to the cervical spine in the course of the combined spa and health resort-based treatment with the use of manual therapy]. AB - AIM: The objective of the present work was to study dynamics of the cognitive function in the school-age children presenting with a natal injury in the cervical region of the spine in the course of the combined spa and health resort based treatment with the use of manual therapy based at a health resort facility. THE PATIENTS AND METHODS: A total of 110 schoolchildren at the age from 8 to 15 years (mean age 13.0 +/- 0.4 years) were examined during the residual period of a natal injury in the cervical region of the spine. All the participants of the study were divided into to randomized groups. The main group was comprised of 55 school-age children (mean age 13.0 +/- 0.4 years) given the comprehensive spa and health resort-based treatment with the application of manual therapy and the group of comparison that contained the remaining 55 schoolchildren (mean age 13.0 +/- 0.4 years) who received the same balneotherapeutic treatment but without manual therapy. We analyzed the indicators of cognitive function after the application of manual therapy in 55 children and adolescents aged from 8 to 15 years who underwent the natal trauma to the cervical spine associatedwith the symptoms of postural disorders of varying severity. RESULTS AND DISCUSSION: The article presents the results of the analysis of cognitive function dynamics in the children and adolescents under the influence of the combined spa and health resort-based treatment with the use of manual therapy of functional blocks. It was shown that the combined spa and health resort-based rehabilitative treatment with the use of the manual therapeutic techniques makes it possible to significantly improve the condition of the cervical spine and exerts the positive influence on the dynamics of the cognitive function, has beneficial effect on the mental and motor functions, increases the flexibility and backup capabilities of the nervous system, and may be instrumental in resolving the problems arising from school disadaptation. PMID- 26841527 TI - [The combined action of drinking mineral water and low-intensity electromagnetic radiation under the immobilization stress conditions (an experimental study)]. AB - The present study carried out on white male rats in experiments with the use of biochemical, radioimmunological, and electron- microscopic methods. It was shown that the combined treatment with potable mineral water (MV) and low-intensity electromagnetic radiation (LIEMR) of ultrahigh frequency (power density less than 1 pW/cm2, the frequency about 1000 MHz) facilitated the activation of metabolic and intracellular regenerative processes in the liver and testes. One of the advantages of the combined application of MV and LIEMR over the single-factor treatment manifested itself as the weakening of stress reactions, the increase in the frequency of the plastic processes, and the more harmonious development of different forms of intracellular regeneration. The results of the study provide a deeper insight ino the mechanisms underlying the combined actions of drinking mineral water and low-intensity electromagnetic radiation; also, they justify the application of these factors for the protection of the reproductive system and the entire body from stress-induced disorders. PMID- 26841528 TI - [The long-term results of the application of the combined rehabilitative treatment in the patients presenting with knee osteoarthrosis]. AB - The rehabilitative treatment of the patients suffering from knee osteoarthrosis (OA) up-to-date remains one of the most important medical and social problems of modern medicine due to the high prevalence of this disease, heavy morbidity, and the significant deterioration of the quality of the patients' life. The objective of the present study was to evaluate the long-term results of the combined application of radon and extracorporeal shock-wave therapy for the rehabilitation of the patients presenting with knee OA. PATIENTS AND METHODS: The study involved 75 patients at the age from 35 to 62 years with the confirmed diagnosis of stage II and III knee osteoarthrosis. They were divided into 3 groups. Those comprising the main group received extracorporeal shock-wave therapy in combination with the treatment based on the use of radon baths. The patients included in the group of comparison were given a course of radon therapy alone while the patients of the control group received the standard treatment including physiotherapy, magnetic therapy, and the use of non-steroidal anti-inflammatory drugs (NSAIDs). RESULTS: The study has demonstrated the high effectiveness of the combined application of the radon baths and extracorporeal shock-wave therapy that was manifested as the substantial decrease of pain intensity, the increased range of motion in the knee joints, and the improvement of the general quality of life. These beneficial effects persisted during a period of up to 12 months. The stable remission was documented in 82% of the patients comprising the main group. CONCLUSION: The data obtained give reason to recommend the method employed in the present study for the extensive practical application at different stages of medical rehabilitation of the patients presenting with knee osteoarthrosis. PMID- 26841529 TI - [Myofascial meridional reflexotherapy of scapulohumeral periarthrosis in the course of the combined spa and health resort-based treatment]. AB - The authors draw attention to the role of a whiplash injury in the pathogenesis of scapulohumeral periarthrosis (SHP). Peculiarities of the specific pathological biomechanical changes associated with this condition are described. The study included a group of 64 patients in whom the localization of the myofascial trigger points (MFTT) of the shortened muscles is described with reference to the differential techniques for soft-tissue manual therapy. Spatial emphasis is laid on the diagnostic dynamic ischemic compression of trigger points (TT) for their inactivation using the method proposed by J. Travel in the original modifications proposed by the authors of the present article. The results of the application of myofascial meridional reflexotherapy of scapulohumeral periarthrosis are presented and analysed in the context of the combined spa and health resort-based treatment. PMID- 26841530 TI - [The external application of "Plastunskaya" fluoride-containing mineral water in the course of the combined spa and health resort-based treatment of deforming osteoarthrosis]. AB - Mineral waters containing fluorine (fluorinated waters) at a concentration in excess of 1 mg per liter are extensively used in the newly developing spa and health resort areas of the Russian Federation. They have been found in Siberia, Trans-Baikal regions, and the Krasnodar Territory (together with the Greater Sochi). These waters are mainly used for drinking as a component of the balneo- therapeutic treatment. In this context, the study of the therapeutic effects of low-mineralized hydrocarbonate-sodium waters containing fluorine in high concentrations is of paramount importance for the substantiation and facilitation of their external application in the framework of the programs of combined spa and health resort-based treatment of various diseases. We have investigated the possibility of the external application of "Plastunskaya" mineral water characterized above all by the high content of fluorine for the external treatment of osteoarthritis in 187 patients at the age varying from 37 to 63 years in the combination with the sparing regimen of physical activity, therapeutic physical exercises, klimatotherapy of moderate intensity, and a balanced diet. The patients were prescribed to take general "Plastunskaya" mineral water baths with the fluoride concentration of 7.4 mg/l at a temperature of 36 C from 7 to 15 minutes in duration for 2 consecutive days with a break on every third day (the total course consisted of 14-16 baths). It was shown that the combined treatment with the use of fluorine-containing mineral water resulted in the significant improvement of the clinical and biochemical parameters characterizing the health status of the patients suffering from deforming osteoarthrosis. PMID- 26841531 TI - [The balneotherapeutic components of sulfide-containing mineral waters]. AB - It has been suggested in an early study that sulfanes may serve as a source of sulfur contained in hydrogen sulfide sources. We have performed derivatization of sulfanes, known to be present in the "Novonukutskaya" mineral water. The presence of polysulfanes in balneotherapeutic sulfide waters was confirmed by the HPLC-UV and chromato-mass spectrometric techniques. Derivatization of inorganic polysulfides was achieved by using the reaction with methyl iodide. It was shown that polysulfanes contained in the examined samples were metastable and disintegrated into So and H2S. Almost all molecular zero-valent sulfur was present in the form of S8. The application of HPLC allowed to determine the equilibrium concentration of molecular sulfur. The presence of the above compounds in therapeutic sulfide waters raises the question of the mechanism of their curative action. The authors hypothesize that it may be related to the high therapeutic potency of the substances obtained by steam distillation from the "Novonukutskaya" mineral water. PMID- 26841532 TI - [The medical rehabilitation of the children presenting with the hyperactive urinary bladder]. AB - The present article is focused on the modern technologies for the medical rehabilitation of the children presenting with the hyperactive urinary bladder (UB) designed to promote the act of urination in the children at all levels of bladder innervation. PMID- 26841534 TI - [Professor I.I. Grigoriev and its contribution to the national balneotherapeutic medicine (on the occasion of his 100th birthday anniversary)]. AB - This work is dedicated to the memory of the eminent Russian health resort expert professor Ivan Ivanovich Grigoriev (1915-2002), the founder of the scientific school of meteoprophylaxis who created the organizational and methodological basis for weather forecasting with the medical implications. Ivan Ivanovich Grigoriev has made a great contribution to the research designed to elucidate the influence of the weather factors on the human body. Moreover, he was a prominent organizer of the health resort business in this country paying especially much attention to the construction of spa and health resort facilities and their therapeutic zonation. He did a lot to substantiate the necessity of spa and health resort-based treatment for the country's population and to develop indications and contraindications for such therapy including the identification of the groups of adult subjects and children who are at an especially high risk of suffering from various diseases. PMID- 26841533 TI - [The application of succine in sports]. AB - The development of energy deficiency in the course of physical exercises that eventually leads to serious derangement of the energy metabolism is an important component of the deterioration of physical and intellectual working capacity. The most promising approach to the correction of impaired physical and intellectual working capacity associated with energy deficiency consists in the application of pharmaceutical preparations containing intermediate products of the tricarbonic acid cycle. Of great promise in this context is succinic acid by virtue of its oxidation in endogenous reactions that constitutes the physiological adaptive mechanism by which resistance of the organism to oxygen deficiency is promoted. PMID- 26841535 TI - [The 70th birthday anniversary of professor Aleksey Mikhailovic Vasilenko, D. Med. Sci., honoured doctor of Russian Federation]. PMID- 26841536 TI - [Completely artificial heart: Contemporary state of the problem]. PMID- 26841537 TI - [Software system for evaluation of the functional state of mother and fetus]. PMID- 26841538 TI - [Magnetoelectric system for rapid healing of trophic ulcers in patients with the diabetic foot syndrome]. PMID- 26841540 TI - [A laser-based intraocular pressure meter]. PMID- 26841539 TI - [Transcranial electrostimulation in treatment of chronic diffuse liver diseases]. PMID- 26841541 TI - [A simulator of the cardiovascular system for testing artificial circulation devices]. PMID- 26841542 TI - [A method for electrodiagnostics of necrocytosis under conditions of experimental pancreatonecrosis]. PMID- 26841543 TI - [The effect of myographic interference and isoelectric line drift on the correlation coefficient in classification of cardiac complexes]. PMID- 26841544 TI - [Use of AFE analog interfaces for parametric evaluation of the degree of syncronization of electrophysiological processes]. PMID- 26841545 TI - [A tracheobronchial nebulizer of new generation]. PMID- 26841546 TI - [A study of workflow irregularity in equipment for DNA sample preparation]. PMID- 26841547 TI - [A study of characteristics of the pathological activity of brain in patients with photosensitive epilepsy exposed to light stimulation]. PMID- 26841549 TI - [Vacuum concentrator of fluid microvolumes]. PMID- 26841548 TI - [A magnetic tracking system for invasive surgical instruments]. PMID- 26841550 TI - [The study of the association of polymorphism rs5219 gene KCNJ11 with obesity and the risk of type 2 diabetes among residents of the Moscow Region]. AB - The study involved 1,050 people living in the Moscow region, including 311 men and 739 women. Genotyping of KCNJ11 rs5219 polymorphisms was performed using allele-specific amplification, result detection in real time and using TaqMan probes complementary to polymorphic DNA regions. Results of the study of KCN11 rs5219 gene polymorphism showed that 14.2% of the patients had TT genotype, 44.8% -CT genotype, 41.0%--CC genotype. The frequency of the mutant T alele was 36.6%, C allele--63.4%. The frequency of the T allele didn't significantly differ in individuals with obesity (BMI >= 30 kg/m2) and individuals with a BMI < 30 kg/m2 (38.8% and 35.7%, respectively), OR--1.14; CI (0.907-1.439), p = 0.26. At the same time, the amount of energy expenditure at rest, calculated per kg lean body weight, and serum content of uric acid in were significantly higher in individuals with KCNJ11 rs5219 polymorphism, both in homo-, and in the heterozygous type. The frequency of the T allele and TT genotype in patients with hyperglycemia was higher than in the comparison group. Genotype TT is associated with type 2 diabetes (OR = 2.35, CI: 1.018-5.43, p = 0.04). PMID- 26841551 TI - [Lead toxicity at its joint administration with nanostructured silica]. AB - Nanoparticles (NPs) are present in the composition of the objects in the environment and foods together with contaminants of conventional nature, and may enhance their toxicity in certain conditions. The aim of this work was to study the effect of nanostructured silicon dioxide (SiO2), widely used as a food additive, on the accumulation and manifestation of the toxic effect of lead (Pb) when co-administered to rats in the subacute experiment. Rats were divided into 6 groups. Animals of the 1st group (control) received distilled water intragatrically by gavage. Rats of the 2nd and 3rd groups received dispersion of SiO2 NPs with primary particle size of 5-30 nm in the doses of 1 and 100 mg/kg body weight, respectively, of Group 4--lead acetate in the dose of 20 mg of lead/kg body weight, group 5 and 6--Pb acetate and SiO2 NPs dispersion in doses, respectively 1 and 100 mg/kg body weight, for 22 days by intragastric gavage. The weight of the body and organs, standard haematological parameters, serum protein, creatinine, uric acid, albumin, glucose level, and -alkiline phosphatase, ALT and AST activity, urinary 5-aminolevulinic acid (ALA) were determined. Hepatocyte apoptosis was studied by flow-cytometry. The content of Pb, cadmium (Cd), arsenic (As), selenium (Se), iron (Fe), zinc (Zn), copper (Cu), chromium (Cr), manganese (Mg), aluminum (Al) and cobalt (Co) in organs (liver, kidney, brain) was determined by ICP-MS. The result showed that the introduction of Pb, but not NPs resulted in a significant increase in the mass of the kidneys and testes. Urinary excretion of 5-ALA in animals from groups 4-6 significantly (p < 0.001) increased, compared with animals 1-3 groups, not influenced by SiO2 NPs administration (p > 0.05). Introduction of SiO2 NPs resulted in a dose-dependent increase in blood hemoglobin, the effect of lead on this index had the opposite direction. Marked changes were noticed in the levels of glucose and serum albumin in combined exposure of Pb and NPs. No additional adverse effect was noticed in Pb co-administration with NPs on haematological parameters and hepatocyte apoptosis. Pb accumulation was revealed in the liver, kidneys and brain in animals of groups 4-6, which was not enhanced by the combined effects of NPs (p > 0.05). The average biosubstrates content of Cd, As, Se, Zn, Cu, Al, Cr, Mn, Co was similar in animals treated and untreated with Pb, and demonstrated no dependence on NPs dose. The only alleged adverse impact on the trace element profile was almost twofold significant increase in the content of Al in the liver in animals treated with lead and SiO2 NPs in the highest dose (0.859 +/- 0.085 mg/kg vs 0.468 +/- 0.065 mg/kg in the 4th group, p < 0.05). In the absence of lead exposure, this effect was not observed. Thus, there wasn't obtained any unequivocal evidence of lead adverse effects potentiation in the case of a joint income with SiO2 NPs. Moreover, for some indicators, such as weight gain, serum AST activity, hemoglobin concentration, erythrocyte parameters, the introduction of the SiO2 NPs "abolished" to a certain extent some of the adverse effects of lead, which may be due to the effects of its enterosorption. Investigation of the influence of different types of NPs on the intestinal absorption and toxicity of various chemical contaminants should be continued. PMID- 26841552 TI - [Epidemiologic aspects of energy drink intake in Russian Federation]. AB - Article examines the impact of 'energy" drinks that have become so popular in recent decades on people. As a research tool a short structured questionnaire was used. It included questions about whether the respondent used "energy" drinks and, if yes, how often; whether he/she had an experience of using it with alcohol; if one is informed about the affect of substances that are included in the drink on the organism; reason of using; the reason of debut consumption; primary feeling during and after consumption; primary feeling after taking a large dose of "energy" drink. Each respondent also pointed out sex and noted whether he/she wanted to learn more about "energy" drinks and effects of their use on the organism. Within 3 years of study 1377 people (682 men and 695 women) aged 12 to 42 were surveyed. The results showed that 89.0% of respondents consumed energy drinks in some to some degree, and from these 7.4% used it constantly (at least 1 can a day). 24,0% of respondents had an experience of taking "energy" drinks with alcohol. With that, the number of men who used "energy" drinks with alcohol, prevails over the same number of women: 60.3% (n = 199) and 39.7% (n = 131), respectively (p = 0.003). Relationship between age of respondents and features of using as well as effects of "energy drinks" was also statistically proven. The elder the group is the less is the number of responders who drinks energetics constantly (Rs = -0.88, p < 0.001), who knows about the affect of caffeine and other substances on the organism (Rs = -0.93, p < 0.001), who drinks energetics forced by desire to get new feelings (Rs = -0.78, p < 0.001), exams (Rs = -0.73, p < 0.001), who feels fatigue (Rs = -0.79, p < 0.001), and get headache (Rs = -0.8, p < 0.001), the more is the number of responders who noticed that the primal feeling after energetics drinking was rising of working efficiency (Rs = 0.76, p < 0.001) and excessive motional activity (Rs = 0.59, p = 0.01). Basing on the data obtained basic principles of reducing the rate of use of energy drinks program were developed. PMID- 26841553 TI - [To the question of rational nutrition, micronutrient status correction, prevention and treatment of iron deficiency in pregnancy]. AB - In the article the features of healthy nutrition in pregnant women suffering from iron deficiency has been discussed. The criteria for diagnosis of anemia during pregnancy, the stage of the disease development, the specifics of iron deficiency during gestation, the need in this trace element in pregnant women have been defined. The necessity of an adequate selection of a balanced diet during pregnancy complicated with anemia has been based. Iron content in food products along with the extent of absorption depending upon the origin of the product have been considered. The compounds that contribute to a better absorption of iron, as well as medicinal substances that prevent its absorption have been presented. Special attention is paid to the questions of preventative measures in preventing anemia in pregnant women. In addition to a balanced diet and iron preparations for treatment and prevention of anemia, the appointment of vitamin-mineral supplements and specialized foods for pregnant enriched with micronutrients has been substantiated. PMID- 26841554 TI - [Evaluation of physical development in children with classical phenylketonuria]. AB - Classical phenylketonuria (PKU) is hereditary disease, which is based on the disturbance of phenylalanine conversion to tyrosine. The basic treatment of PKU is low phenylalanine diet. Prolonged restriction of natural protein may have a negative impact to PKU patient growth and physical development. The objective was to evaluate the physical development of patients with classical PKU at birth and on the diet based on the products with different chemical composition without phenylalanine. 257 PKU patients have been examined with the computer program "WHO Anthroplus 2009". All patient were born at term. Z-score of body weight, height and body mass index (BMI) to age has been retrospectively estimated. Patients were divided into 2 groups: group 1--101 children born in 1980-1993 were fed by unadapted specialty products based on protein hydrolyzate with restricted phenylalanine, and group 2--156 children born in 1995-2012 were fed by contemporary amino acid mixtures without phenylalanine. All newborn PKU patients had the middle for age Z-score of weight and BMI, 21% of neonates had high Z score growth. Before the diet therapy BMI Z-score was normal in 84.1% patients in group 1 and 87.2% patients of group 2. After 6 mo of treatment with low phenylalanine diet the number of patient with normal BMI Z-score was 71.3% in group 1 against 95.6% in group 2. Thus, using of modern amino acid mixtures without phenylalanine, enriched with essential nutrients can promote the normal physical development of PKU patients. PMID- 26841556 TI - [Effectiveness of the program "School Milk" for the prevention of iodine deficiency]. AB - Republic of Bashkortostan refers to iodine-deficient regions of Russia. The incidence of endemic multinodular goiter in 2012 in the Republic amounted to 33.2 per 100 thousand of the population. The purpose of the study is to evaluate the effectiveness of group iodine prophylaxis of schoolchildren through the use of iodized milk. The study included 181 children of primary school (pre-pubertal) age (8-10 years), it has been carried out in accordance with the recommendations of the WHO and the International Council for Control of iodine deficiency disorders using a unified system of identification of iodine deficiency states. Level of physical development was assessed according to anthropometric measurements, which were conducted by centile distribution tables according to age and sex, and the individual assessment of physical development was determined by the level of feature by its position in a number of centile. Assessment of iodine deficiency was carried out by determining levels of iodine excretion in a single urine sample. Iodine concentration in urine was determined by ceric ion arsenious acid method. Frequency of iodine deficiency varying degrees before the iodine prophylaxis among urban children was 57.0%, among rural-92.3%. Urban junior schoolchildren showed severe iodine deficiency in 12.7% and moderate one in 16.4% of the cases, while in the countryside their prevalence was higher--27.4 and 35.2%, respectively. It was revealed that the number of children whose body growth values are within the average values is 36% in urban children, and 48.4% in rural areas. It should be noted that the low and very low body height predominate in rural students, it makes up 16.1% (while in the town it makes-up 2.3%). Iodine prophylaxis contributed to a significant reduction of iodine deficiency in children. In the town the median urinary iodine exceeded 100 mg/L and amounted to 159.4 mg/L. After iodine prophylaxis 82.5% of urban children and 72.1% of rural showed normal urinary iodine. When comparing the results of clinical and laboratory studies before and after the group prevention of iodine deficiency there has been revealed a positive trend in terms of reflecting the tensions of thyroid status. PMID- 26841555 TI - [Assessment of the North resident's nutrition supply with view of the content of macro- and microelements in food]. AB - In order to study the body nutrition supply in 17-37 year-old Magadan residents, among them Europeans (control group, n = 200) and Indigenous Minorities of the North (IMN, n = 56), we examined hair samples of the subjects and ascertained the content of 25 essential minerals and trace elements using the method of atom emission and mass spectrometry with the inductively bonded argon plasma. At the same time, these elements were detected un drinking water and in local food products including samples of muscles and milt (testes) of salmon (Salmoidae), fished out in the Okhotsk Sea near shore. When comparing the values of the examined male Europeans and subjects IMN, the latter demonstrated reliably higher Ca (373.37 mcg/g vs. 256.72 mcg/g), Mg (34.09 mcg/g vs. 24.89 mcg/g), P (184.30 mcg/g vs. 157.60 mcg/g), I (1.13 mcg/g vs. 0.50 mcg/g); in the examined females- Mg(56.66 mcg/g vs. 32.30 mcg/g) and P (181.35 mcg/g vs. 149.40 mcg/g). Besides, the IMN examinees, both males and females, demonstrated reliably lower Fe values in comparison with the control group. When comparing male and female subjects, we found the first ones to be reliably higher in As, Cr, K, Na, I, Cd and Li but lower in Ca, Co, Mg and Mn. The present study provides data on the content of minerals and trace elements in some food products, widely represented in food ration of the residents of Magadan town. Interspecies differences in the content of chemicals also conformed to the maximum permissible concentration approved for food products, but Co, Cu, Na and Zn values in Chum salmon proved to be reliably higher than those in Coho salmon. Fe levels being within 3.8-4.9 mcg/g were practically similar to fresh-water fish. The contents of K and P in the examined fish species were found as rather significant (3448-8879 mcg/g and 2795-3535 mcg/g, respectively). PMID- 26841557 TI - [Micronutrient composition of grape growing in Dagestan]. AB - Micronutrient content in Pearl Zala, Pearl Saba, Creamy, and Amber Muscat varieties of grape has been determined. The ultimate analysis has been made by the atomic-absorption flame photometry; ascorbic acid has been determined by the titrometric analysis; rutin, niacin, and carotene have been studied by the colorimetric method. It has been found that the content of potassium (2673.8 mg/kg), calcium (349.0 mg/kg), iron (35.9 mg/kg), silicon (611.3 mg/kg), manganese (0.89 mg/kg) and vitamin C (5.3 mg/dm3) was the highest in Pearl Zala grapes, while the content of zinc (0.31 mg/kg), nicotinic acid (10.9 mg/dm3) and carotene (0,33 mg/dm3) was the highest in Pearls Saba. Amber Muscat grape has been found to have the highest concentration of sodium (151.4 mg/kg), phosphorus (466.8 mg/kg), magnesium (221.6 mg/kg), aluminum (68.5 mg/kg), cobalt (0.120 mg/kg) and copper (1.91 mg/kg) in comparison with other grape varieties. It has been found that the content of ascorbic acid and rutin differ 1.5-1.6 fold, of magnesium, iron, silicon and potassium--1.7-1.8 fold, of calcium and phosphorus- 2.2-2.5 fold, carotene--4.1 times, aluminum, sodium and nicotinic acid--4.7-5.5 fold, cobalt and copper--8.6-8.7 fold, zinc and manganese--10.3-22.2 fold. PMID- 26841558 TI - [Antioxidant and antiradical properties of red grape wines]. AB - The article presents the results of studies of the antioxidant and antiradical capacity of red table wines. It is shown that the antioxidant and antiradical properties of red wines due to the varieties of grapes and processing technologies. A correlation between the concentration of phenolic components of the complex and antiradical properties, as well as antioxidant and antiradical properties of red wines has been established. Antioxidant and antiradical properties were higher in variants with the highest concentration of the most important components of a phenolic complex--catechins and tannins. Their greatest content has been identified in the wine materials Saperavi made on technologies which can extract components polyphenol complex not only from grape skin, and grape seed (seed) containing ellagitannins and gallocatechin (using Vinificator company Padovan; prepared by fermenting mash irrigation heated mash, using a fermentation mash by Fludase). Depending on the grape varieties and production technology, the antioxidant activity varied by more than 30%. These data indicate that the technology can increase the production of wine intravarietal (for grapes) antioxidant activity of 10 to 20%. PMID- 26841559 TI - [Standardization of the method of osmolality determination of specialized foods]. AB - Binding requirements for the application and enforcement at the customs territory for specialized food products have been installed in the established documents of the Customs Union. The category of specialized foods consists of food products for babies, for pregnant and lactating women, dietary products (clinical and preventive nutrition), sport nutrition. In addition to the General safety requirements that must be met by specialized food products, the value of osmolality must be regulated in some kinds of such products. The specialists of Institute of Nutrition developed national standard "Specialized foods. Method of osmolality determination" for the purpose of standardization of a method of osmolality determining. Product samples for baby and sport nutrition which are realized on domestic market have been researched. Specialized products for baby food had osmolality from 290 to 327 mOsm/kg, that corresponded to the requirements of regulatory documents applicable to this product group. Osmolality of carbohydrate and mineral drink for athletes was in the range from 308 to 330 mOsm/kg, confirming their belonging to the isotonic drinks. The method can be used in researches for developing of the new products with specific predetermined chemical composition and in clinical practice for the osmolality control of products for enternal nutrition. PMID- 26841560 TI - [Non-enzymatic glycosylation of dietary protein in vitro]. AB - Non-enzymatic glycosylation of proteins, based on discovered by Mayarn reaction of carbohydrate aldehyde group with a free amino group of a protein molecule, is well known to experts in biochemistry of food industry. Generated brown solid in some cases give the product marketable qualities--crackling bread--in others conversely, worsen the product. The biological effects of far-advanced products of non-enzymatic protein glycosylation reaction have not been studied enough, although it was reported previously that they are not split by digestive enzymes and couldn't be absorbed by animals. The objective of this work was to compare the depth of glycosylation of different food proteins of animal and vegetable origin. The objects of the study were proteins of animal (casein, lactoglobulin, albumin) and vegetable (soy isolate, proteins of rice flour, buckwheat, oatmeal) origin, glucose and fructose were selected as glycosylation agents, exposure 15 days at 37 degrees C. Lactoglobulin was glycosylated to a lesser extent among the proteins of animal origin while protein of oatmeal was glycosylated in the least degree among vegetable proteins. Conversely, such proteins as casein and soya isolate protein bound rather large amounts of carbohydrates. Fructose binding with protein was generally higher than the binding of glucose. The only exception was a protein of oatmeal. When of glucose and fructose simultaneously presented in the incubation medium, glucose binding usually increased while binding of fructose, in contrast, reduced. According to the total amount of carbohydrate (mcg), which is able to attach a protein (mg) the studied food proteins located in the following order: albumin (38) > soy protein isolate (23) > casein (15,) > whey protein rice flour protein (6) > protein from buckwheat flour (3) > globulin (2) > protein of oatmeal (0.3). The results obtained are to be used to select the optimal combination of proteins and carbohydrates, in which the glycosylation during storage will be minimal. PMID- 26841561 TI - [Milk fat globules, as determinants of the nutritional and biological value of goat milk]. AB - This review summarizes the most complete information on such fundamentally important quality parameters of goat milk as the cellular composition of somatic cells and the structure of cytoplasmic debris in milk. It also focuses on the characterization of an essential component of the energetic value and nutritional content of milk--milk fat globules and milk fat globule membranes. The survey also clarifies some of the terms and meanings of physiological processes associated with the formation of the milk of various ruminants and breast milk. PMID- 26841563 TI - [Vladimir Borisovich Spirichev (to the 85th anniversary of the birth)]. PMID- 26841565 TI - New band 4 role set to be created. PMID- 26841564 TI - "Associate nurses' could ease the staffing crisis. PMID- 26841566 TI - Fifth of universities report issues with the capacity of placements. PMID- 26841567 TI - Charity calls for donations to fight nurses' fuel poverty. PMID- 26841568 TI - Osborne plugs funding gap for Seacole statue. PMID- 26841569 TI - Nurses protest against decision to end free student education. PMID- 26841570 TI - Universities push for student loan repayment facility for new nurses. PMID- 26841571 TI - Health education budget freeze could 'limit placement funding'. PMID- 26841572 TI - Training reforms 'will not fix the nurse shortage'. PMID- 26841573 TI - Capped agency pay rates come into operation. PMID- 26841574 TI - Trust recruits more staff than it has vacancies in bid to fill posts. PMID- 26841575 TI - "A national strategy is vital to futureproof older people's care". PMID- 26841577 TI - Learning disabilities: reducing inequalities. AB - This article introduces five small changes that nurses who do not usually work in the field of learning disabilities can make to improve healthcare and reduce avoidable, premature deaths of people with learning disabilities. The changes are small, cost little and enable nurses to creatively meet the needs of their patients. PMID- 26841576 TI - "By investing in staff education we can tackle dementia head on". PMID- 26841578 TI - Learning disabilities: improved bowel screening. AB - Bowel cancer is the second most common cause of cancer death in the UK but it can be successfully treated if detected at an early stage. In 2006 the NHS Bowel Cancer Screening Programme was introduced to everyone aged 60-74 years in England. This article describes how South Tyneside NHS Foundation Trust community Learning Disability Service addressed the bowel screening needs of those people with a learning disability in Gateshead and South Tyneside. A project was developed to improve and increase the uptake of bowel screening for this population group. PMID- 26841579 TI - Revalidation: continuing professional development. PMID- 26841580 TI - Peritoneal dialysis: a guide for non-renal nurses. AB - Peritoneal dialysis allows patients living with Stage 5 chronic kidney disease to manage their disease at home. However, such patients may be admitted to hospital with various health problems and be cared for by ward nurses who have not specialised in renal care. Part 1 of this series outlined the causes of chronic kidney disease and described how PD works; this article provides the information nurses need to better support such patients. PMID- 26841581 TI - Selecting wound dressings for optimum healing. AB - This article, the fifth in a six-part series on wound management, discusses wound dressings. There are a multitude of dressings to choose from and selecting the right one is crucial to promoting healing, as the wrong dressing can significantly hinder a wound from healing. A good understanding of how wounds heal, the dressings available and how they work should enable nurses to make an appropriate selection. The final article in the series is about wound complications and how to deal with them. PMID- 26841582 TI - 60 SECONDS WITH Helen Shepherd. PMID- 26841583 TI - 'Nursing is a privilege'. PMID- 26841584 TI - [Source Contribution Analysis of the Fine Particles in Shanghai During a Heavy Haze Episode in December, 2013 Based on the Particulate Matter Source Apportionment Technology]. AB - The haze pollution caused by high PM2.5 concentrations has become one of the major environmental issues restricting urban and regional sustainable development in China in recent years. Therefore, the diagnosis of the pollution sources of PM2.5 and its major components in a scientific and efficient way is of great significance both scientifically and theoretically. A rare heavy haze pollution event occurred in Shanghai and the surrounding Yangtze River Delta in early December, 2013, that the hourly PM2.5 concentration reached 640 MUg x m(-3). In this study, we analyzed the three typical episodes that occurred in Shanghai during this period. The particulate matter source apportionment technology (PSAT) was applied to study the source contributions to PM2.5 and its major components. Results showed that NO3-(2.5) were mostly contributed by industrial boilers and kilns, transportation and power plants. Comparatively, most of the SO4(2-) 2.5 came from industry and transport sectors. During the three episodes including haze, foggy haze and transport, local emissions contributed 35.3%, 44.8%, 22.7%, while super-regional transport accounted for 42.0%, 41.1% and 59.8% to PM2.5, respectively. In the YRD modeling domain, fugitive dust, industrial processing, volatile source, industrial boilers and kilns and transport were the major contributors to high concentrations of PM2.5, with the average contributions of 25.1%, 14.9%, 15.8%, 13.7% and 15.9%, respectively. Results showed that the very heavy haze pollution is usually not caused by a single city, the regional joint pollution control is of great importance to relieve the pollution level. PMID- 26841585 TI - [Transformation Mechanism and Sources of Secondary Inorganic Components in PM2.5 at an Agriculture Site (Quzhou) in the North China Plain in Summer]. AB - Simultaneously on-line measurements of major water-soluble inorganic ions and gaseous pollutants were performed from June 9 to July 11, 2014 at Quzhou, an agriculture site in the North China Plain using a gas-aerosol collector (GAC) and ion chromatograph (IC), aiming to track the diurnal variation rule of secondary inorganic components and gas-phase precursors as well as their interactions. The transformation mechanism and sources of fine particles (PM2.5) were also discussed. The results showed that these water-soluble ions in PM2.5 and their gas-phase precursors varied regularly. As the dominant ionic components of PM2.5 (accounting for 76.23%), the average concentrations of SO4(2-), NH4(+), NO3(-) were 26.28 MUg x m(-3), 18.08 MUg x m(-3) and 16.36 MUg m(-3) respectively. Among the precursor gases, the NH3, generated from the discharges of local agricultural activities, displayed a significantly higher concentration at an average value of 44.85 MUg x m(-3). The average fine sulfate and nitrate oxidation ratios (SOR and NOR) were SOR = 0.60, NOR = 0.30, revealing the remarkable characteristics of secondary pollution. As could be found from the relevant analysis, the NH4(+) of Quzhou showed well relations with NO3(-) and SO4(2-), and the environment here was rich of ammonia. The NH4(+) existed in the form of (NH4)2SO4 and the generation of NO3(-) was limited by the HNO3. From the analysis for the equilibrium of NH4NO3, we observed that the atmospheric environment of Quzhou was adverse to the generation and maintenance of NH4NO3 during the daytime,in contrast with the night. Integrated with the study, the results displayed that the secondary transformation was the main source of fine particles in Quzhou, and the NH3 from field and compost was the significant factor leading to the high value of S-N-A. PMID- 26841586 TI - [Pollution Level and Sources of Organic Phosphorus Esters in Airborne PM2.5 in Chengdu City]. AB - Organic phosphorus esters ( OPEs ) in atmospheric PM2.5 in Chengdu city was quantitatively determined by using gas chromatography-mass spectrometry. The distribution characteristic was discussed, back trajectory model and correlation analysis were used to study the sources of OPEs in PM2.5 in Chengdu city. The results showed that the annual average concentration of Sigma7OPEs in atmospheric PM2.5 in Chengdu city was 6.46 ng x m(-3) for the urban site and was 9.38 ng x m( 3) for the suburb site. Due to the waste material recycling industries in the suburb area and the perennial dominant wind direction in Chengdu, the concentration of Sigma7OPEs at suburb site was higher than that at urban site (P = 0.013). The atmospheric mixed degree influenced the distribution of OPEs in rural and urban area. The source of Sigma7OPEs in atmospheric PM2.5 in Chengdu city was mainly from endogenous pollution which was mainly affected by the local sources around the samoling sites. while the contribution of the exogenous pollution was small. PMID- 26841587 TI - [Simulation Study of the Emission of Polycyclic Aromatic Hydrocarbons and Sugar Alcohols from Biomass Burning]. AB - To measure the emission factors of PM2.5 and its associated PAHs and sugar alcohols, Chinese red pine stick and four crop straw including rice, wheat, corn and cotton were burned in a chamber. In addition, the kinetics of certain compounds were obtained through the irradiation of the glass filters with PM2.5 loading by 500 W mercury lamp. The emission factors of PM2.5 were ranged from (2.26 +/- 0.60) g x kg(-1) (Chinese red pine stick) to (14.33 +/- 5.26) g x kg( 1) (corn straw). Although the emission factors of the total 19 PAHs differed from (0.82 +/- 0.21) mg x kg(-1) (Chinese red pine stick) to (11.14 +/- 5.69) mg x kg( 1) (cotton straw), 4 ring PAHs showed predominance over other PAHs accounting for 51% - 71% except Chinese red pine in which retene was the predominant compound. The emission factors of 9 sugar alcohols were ranged from (52.34 +/- 50.16) mg x kg(-1) (rice straw) to (238.81 +/- 33.62) mg x kg(-1) (wheat straw) with levoglucosan accounting for 72% - 96% of the total sugar alcohols. Both the selected PAHs and levoglucosan associated with PM2.5 followed the first order kinetics. The photolysis kinetic coefficient of PAHs (ring number >= 4) was decreased with the increase of PAHs loading in filters. Two PAHs source characteristic ratios such as Flua/( Flua + Py) and IP/(IP + BgP) were relative stable during the irradiation. The photolysis kinetic coefficient of levoglucosan (0.004 5 min(-1)) was comparable to benzo[a]anthracene (0.004 1 - 0.005 0 min( 1)). PMID- 26841588 TI - [Characteristics and Parameterization for Atmospheric Extinction Coefficient in Beijing]. AB - In order to study the characteristics of atmospheric extinction coefficient in Beijing, systematic measurements had been carried out for atmospheric visibility, PM2.5 concentration, scattering coefficient, black carbon, reactive gases, and meteorological parameters from 2013 to 2014. Based on these data, we compared some published fitting schemes of aerosol light scattering enhancement factor [ f(RH)], and discussed the characteristics and the key influence factors for atmospheric extinction coefficient. Then a set of parameterization models of atmospheric extinction coefficient for different seasons and different polluted levels had been established. The results showed that aerosol scattering accounted for more than 94% of total light extinction. In the summer and autumn, the aerosol hygroscopic growth caused by high relative humidity had increased the aerosol scattering coefficient by 70 to 80 percent. The parameterization models could reflect the influencing mechanism of aerosol and relative humidity upon ambient light extinction, and describe the seasonal variations of aerosol light extinction ability. PMID- 26841589 TI - [Photocatalytic Degradation of Gaseous Toluene by a Photo-Fenton Reaction]. AB - In this study, the performance of photo-Fenton reaction on decomposition of toluene was investigated by a flowing column using toluene as a representative of volatile organic pollutants (VOCs). The effects of initial pH, H2O2 concentration, Fe2+ concentration, initial concentration of toluene on degradation of toluene by photo-Fenton reaction were evaluated. Mass spectrometry and gas chromatograph were utilized to detect the products. The results showed that the introduction of UV greatly enhanced the Fenton reaction by improving the generation of hydroxyl radicals. When the initial concentration of toluene was 260 mg x m(-3), the toluene removal can achieve 98% under the following experimental conditions: initial pH = 3.0, H2O2 20 mmol x L(-1), Fe2+ 0.3 mmol x L(-1). Furthermore, no other intermediate except CO2 was detected in the reaction that photocatalytic degradation of toluene in waste gas by the photo-Fenton, which indicates all the degraded toluene was mineralized into CO2. PMID- 26841590 TI - [Emission of PCDD/Fs from Crematories and Its Influencing Factors]. AB - To analysis the influencing factors for the emssions of polychlorinated dibenzo-p dioxins and dibenzofurans (PCDD/Fs) as structure of crematory, air pollution control device (APCD) and funeral objects, etc, we collected and measured the PCDD/Fs emissions in flue gas from 13 crematories in China. Then we proposed some supervision suggestions on measures of pollution control and management. The results indicated that the emission levels of PCDD/Fs (as the toxic equivalent concentration, TEQ) was ranged in a large gap from 0.027 to 15.8 ng x m(-3), and the average was 3.2 ng x m(-3). Emissions factor of PCDD/Fs (as TEQ) from 13 crematories varied between 45.9 and 22 236 ng x body(-1), and the average was 4 738 ng x body(-1). The emissions of PCDD/Fs from flat incinerators were generally lower, whereas higher ratio up to the national discharge standard, than that of car type incinerators. Congener distribution of PCDD/Fs in flue gas from 13 crematories were different from each other. Since the emission of PCDD/Fs from some crematories remains in high level, it is necessary to control pollution from the source, improve the pollution control technology, and strengthen government supervision, by following measures: 11 cremating funeral objects separately from corpse; 22 adding one PMID- 26841591 TI - [Odor Emission Characteristics from Biochemical Treatment Facilities of Kichen Waste in China]. AB - Xining, Ningbo and Beijing were closen as the representative cities about biochemical treatment of kichen waste. The treatment facilities of these cities were investigated and set as the sampling points. The main compositions and the material contents were analyzed by GC/MS, the odor concertration was obtained by the Triangle odor bag method. The results showed that oxygenated hydrocarbons including alcohol, aldehyde, ketone, ester were higher than others in the odor gases, however, the largest contribution to odor pollution were sulfocompounds and the 2nd materials were terpenes; According to the research of the three enterprises, ethyl alcohol, limonene, sulfuretted hydrogen, methyl mercaptan, dimethyl sulfide, dimethyl disulfide, acetaldehyde and ethyl acetate were likely to be considered as the typical odorants from the biochemical treatment facilities of kichen waste. PMID- 26841592 TI - [Temporal and Spatial Characteristics of Lake Taihu Surface Albedo and Its Impact Factors]. AB - Lake surface albedo determines energy balance of water-atmospheric interface and water physical environment. Solar elevation angle, cloudiness, wind speed, water quality and other factors can affect lake surface albedo. Using solar radiation, wind speed, and water quality data (turbidity and chlorophyll-a concentration) which were observed in four eddy covariance sites (Meiliangwan, Dapukou, Bifenggang and Xiaoleishan i. e. MLW, DPK, BFG and XLS) in Lake Taihu and clearness index (k(t)), the influence of these factors on Lake Taihu surface albedo and the reasons that led to its spatial difference were investigated. The results showed that solar elevation angle played a leading role in the diurnal and seasonal change of lake surface albedo; lake surface albedo reached two peaks in 0 < k(t) < 0.1 and 0.4 < k(t) < 0.6 respectively, when solar elevation angle was below 35 degrees. The surface albedo increased with the increasing wind speed, turbidity and chlorophyll-a concentration. However, wind could indirectly affect surface albedo through leading to the changes in sediment resuspension and chlorophyll-a distribution. The sequence of albedo in the four sites was XLS > BFG > DPK > MLW. XLS and BFG belonged to the higher albedo group, while DPK and MLW belonged to the lower albedo group. The different biological environments caused by aquatic macrophytes and algae resulting in the spatial variation of Lake Taihu surface albedo. The relationship between albedo and chlorophyll-a concentration was not a very sensitive factor for indicating the outbreak of algae. This study can provide theoretical reference for lake albedo parameterization. PMID- 26841593 TI - [Remote Sensing Inversion of Diffuse Attenuation Coefficient in Lake Taihu Based on the GOCI Images]. AB - Diffuse attenuation coefficient (K(d)) is an important parameter in water body optics. The spectral characteristics of K(d) in Lake Taihu and its impact factors were analyzed using the in situ measured data from 2006-2009. Then, empirical models and semi-analysis models were built based on the GOCI data to estimate K(d), in order to find a suitable retrieval model for GOCI and analyze the spatial and temporal variations of diffuse attenuation coefficient in Lake Taihu. The result indicates that: (1) The main impact factor of diffuse attenuation coefficient at 490 nm is the non-algal particles absorption coefficient, and the combination model with GOCI bands 4, 5 and 7, namely the near infrared band, the red band and the green band, has the highest precision for the inversion of K(d) (490); (2) the range of K(d) of Lake Taihu distributes between 0 to 15 m(-1), and that can be divided into three levels generally, i. e., the range of the low value between 0-4 m(-1), the range of the medium value between 4-8 m(-1), and the range of the high value between 8-15 m(-1). While, occasionally, some values are higher than 15 m(-1); (3) the K(d) of Lake Taihu distributes with notable spatial and temporal difference. At the view of spatial distribution, the K(d) values get higher from the east to the west of Lake Taihu; from the perspective of time, the K(d) is relatively high in the morning and then shows a tendency of gradually reduce with the time. PMID- 26841594 TI - [Porewater Dissolved Methane in Cyperus malaccensis Marshes Along Salinity Gradient in the Minjiang River Estuary]. AB - Physicochemical properties of soil and dissolved methane concentrations of porewater in the sediments of the Cyperus malaccensis marshes along a salinity gradient in the Minjiang River estuary were evaluated, and the spatial-temporal characteristics and main impact factors were discussed. The average concentrations of dissolved methane in porewater were 331.18, 299.94 and 638.58 MUmol x L(-1), respectively in the Shanyutan, Bianfuzhou and Xiayangzhou wetlands in summer. In the winter, they were 9.04, 266.67 and 322.68 MUmol x L(-1), respectively. The dissolved methane concentration in porewater was higher in summer than those in winter (P < 0.05). Overall, the concentrations of dissolved methane in porewatdr showed an increasing trend from brackish to freshwater marshes. Multivariate statistics analysis showed that the concentrations of dissolved methane in porewater was positively correlated with soils temperature and DOC (P < 0.05), but negatively correlated with soils pH, salinity, and the concentrations of porewater SO4(2-) and Cl-. Spatial-temporal distribution of porewater dissolved methane in estuarine marshes represents a final result of multiple factors, including soil physicochemical properties and hydrodynamic condition. PMID- 26841595 TI - [Stable Isotopes Characters of Soil Water Movement in Shijiazhuang City]. AB - In this study, we analyzed the stable hydrogen and oxygen isotope values of precipitation, soil water, irrigation water that collected in Shijiazhuang City from April 2013 to May 2014 to investigate the changing rule of the stable isotopes in different soil profiles and the process of soil water movement according to using the isotope tracer technique. The results showed that the mean excess deuterium of the local precipitation was -6.188 5 per thousand. Those reflected that the precipitation in Shijiazhuang City mainly brought by the monsoon from the ocean surface moisture, and also to some extent by the local evaporation. Precipitation was the main source of the soil water and the irrigation water played the supplementary role. In the rainy season, precipitation was enough to supply the soil water. The stable oxygen isotopes at 10-100 cm depth decreased with the increase of depth, the maximum depth of evaporation in the rainy season reached 40 cm. The peak of stable oxygen isotopes of soil water pushed down along the profile, which was infected by the interaction of the precipitation infiltration, evaporation and the mixing water. PMID- 26841596 TI - [Seasonal Variations in Vertical Profile of Hg Species and the Influential Factors in Changshou Reservior]. AB - The vertical distribution of mercury (Hg) species were investigated in water and porewater of Changshou reservoir during the period from September 2013 to July 2014. Water samples were collected seasonally from five sampling sites, and the concentrations of Hg species were evaluated. Diffusion fluxes of Hg from sediment to overlaying water were also obtained. The results showed that the average concentrations of total Hg and total methylmercury (MeHg) were (14.77 +/- 12.24) ng x L(-1) and (0.41 +/- 0.47) ng x L(1), respectively. The concentrations of dissolved MeHg (DMeHg) was highest in 4-8 m under surface water, and then decreased with the increasing water depth with a subsequent increase in the bottom of Changshou Reservior. Peak particulate MeHg (PMeHg) values were found in 8-20 m under surface water, but not in the interface of sediment-water, suggesting that the increasing PMeHg might be related to the deposition of MeHg adsorbed to particulates from upper water. Two peak MeHg levels in pore water appeared in 16 and 28 cm under sediment surface, probably due to the extension of living region for sulfate reduction bacteria (SRB) to deeper sediment which resulted in increased methylation rate there. The diffusion fluxes of DMeHg from pore water to overlaying water were 28.2 ng x (m2 x d)(1) and 30.0 ng x (m2 x d)( 1) in autumn and summer, which were significantly higher than that in winter 3.8 ng x (m2 x d)(-1). It may be associated with the higher temperature in those two seasons. An obvious negative correlation was observed between DMeHg and dissolved oxygen (DO) in summer and spring (r = -0.482**, P < 0.05; r = -0.339, P < 0.01); however, similar correlations were not found in autumn and winter. PMID- 26841597 TI - [Nutrient Characteristics and Nitrogen Forms of Rhizosphere Soils Under Four Typical Plants in the Littoral Zone of TGR]. AB - The Three Gorges Reservoir (TGR), which is the largest water conservancy project ever built in tne world, produced a drawdown area of about 348.93 km2 because of water level control. The biological geochemical cycle of the soil in the drawdown zone has been changed as the result of long-term winter flooding and summer drought and vegetation covering. The loss of soil nitrogen in the drawdown zone poses a threat to the water environmental in TGR. Pengxi river, is an important anabranch, which has the largest drawdown area has been selected in the present study. The four typical vegetation, contained Cynodon dactylon, Cyperus rotundus, Anthium sibiricum and Zea mays L. as the control, were studied to measure nutrient characteristics and nitrogen forms of rhizosphere and non-rhizosphere soils in three distribution areas with different soil types (paddy soil, purple soil and fluvo-aquic soils). The variables measured included organic matter (OM), total nitrogen (TN), total phosphorus (TP), total potassium (TK), hydrolysis N, available P and available K, pH, ion-exchangeable N (IEE-N), weak acid extractable N (CF-N) , iron-manganese oxides N (IMOF-N), organic matter sulfide N (OSF-N), added up four N forms for total transferable N (TF-N) and TN minus TF-N for non-transferable N (NTF-N). The results showed: (1) pH of rhizosphere soil was generally lower than that of non-rhizosphere soil under different vegetation in different type soils because the possible organic acid and H+ released form plant roots and cation absorption differences, and the OM, TP, TN and hydrolysis N of rhizosphere soil were generally higher than those of non-rhizosphere soil, and that the enrichment ratio (ER) of all the four nutrient indicators showed Cyperus rotundus > Cynodon dactylon > Zea mays L. > Anthium sibiricum. Available P showed enrichment in the rhizosphere of three natural vegetations but lose under corn, and available K, TK showed different ER in different conditions. (2) IEF-N CF-N, IMOF-N, OSF-N and TF-N of rhizosphere soil were generally higher than those of non-rhizosphere soil, but the TF-N to TN ratio in rhizosphere of Cyperus rotundus and Cynodon dactylon were lower than those of non-rhizosphere soil, and in rhizosphere of Anthium sibiricum and Zea mays L. were higher, the rhizosphere effect of different vegetations on the N cycle was significant difference. (3) the correlation between nutrient characteristics and nitrogen forms was evaluated to explore the influence factor for the N forms changing. There was a significant correlation between soil OM and four N forms, TP was significantly correlated with CF-N, OSF-N, TF-N, and soil available P content was significantly negatively correlated with IMOF-N, OSF-N, TF-N and TN. Our research could provide that the drawdown zone covered with Cyperus rotundus and Cynodon dactylon was better than Anthium sibiricum and Zea mays L. to improve soil N holding and fixation. The vegetation recovery in the drawdown zone should consider the rhizosphere effect of different vegetations on N cycle. PMID- 26841598 TI - [Exchange Fluxes and Coupling Relationship of Dissolved Inorganic Carbon and Dissolved Organic Carbon Across the Water-Sediment Interface in Lakes]. AB - In this work, the exchange fluxes and coupling relationship of dissolved inorganic carbon (DIC) and dissolved organic carbon (DOC) were investigated across the water-sediment interface in Lake Wuliangsuhai and Daihai by employing columnar simulation method. The results showed that the sediments in non Phragmitescommunis area from Lake Wuliangsuhai functioned as the sources of DIC and DOC for overlying water, whereas the sediments from Lake Daihai as the sinks during the period of summer (90 days). In the experimental period, the average exchange rates of DIC and DOC were 71.07 mmol x (m2 x d)(-1) and 185.09 mmol x (m2 x d)(-1) in non-Phragmitescommunis area from Lake Wuliangsuhai, respectively; while in Lake Daihai, they were 155.75 mmol x (m2 x d)(-1) and -1478.08 mmol x (m2 x d)(-1) in shoal water zone, and -486.53 mmol x (m2 x d)(-1) and -1274.02 mmol x (m2 x d)(-1) in deep water zone, respectively. The coupling effects between DIC and DOC were governed by hydrobios, microbial uptake, abiotic and microbiological degradation in Lake Wuliangsuhai and in shoal water zone of Lake Daihai; while they were closely related to the coprecipitation process of CaCO3 and the fraction distribution of inorganic carbon in sediments in deep water zone of Lake Daihai. In summary, the sink or source functions of sediments could be considered as the results of synthetic action of lake types, offshore distance, geohydrochemistry and the fraction distribution of inorganic carbon. PMID- 26841599 TI - [Mass Transport in Porous Sediments During a Turbulent Disturbance]. AB - To examine mass transport in porous sediments during a turbulent flow, we established a simple sediment re-suspension device, made use of different sizes of sands as homogeneous sediments, and we injected 500 MUg x cm(-3) soluble Rhodamine B into different parts of the sediment as the mass tracer, to observe mass transport during the turbulent condition. The research showed that in porous sediments, pore-water pressure difference would be generated because of the sediments' distinctive porosity and permeability, and further led to the convective flow and mass transport in porous media. Moreover, such mass transport was directly influenced by its burial depth and particle size of the sediment. While in homogeneous sediments, mass transport was strongly influenced in vertical direction under 200 r x min(-1) disturbance, and when moderately increased the size of porous particles under the same turbulent condition, such convection of pore-water would relatively enhance. PMID- 26841600 TI - [Characterization of Pollutant Wash-off in the Urban Stormwater]. AB - To understand the pollution character of urban road runoff, the concentrations of TSS, EC, N and P in the ring road runoff of Beijing from June to September 2013 were evaluated, the correlations among pollutants were examined, and the load of TSS, N and P were estimated. Result showed that the small particulates in the range of 1-10 MUm consisted of 60% TSS in the road runoff. Totally 89 percent of the nitrogen (N) was dissolved phase state in the road runoff, 80 percent of the phosphorus (P) was particular phase state in the road runoff. Based on the characteristics of correlations between EC, TSS and TN, TP, EC and TSS were the surrogate indexes of pollution degree assessment for the dissolved N and particulate P in the urban road runoff, respectively. Based on our results, the SS, N and P year load per unit area in Beijing ring road runoff were 16 725.69, 1777.91 and 24.23 mg x (m2 x a)(-1), respectively. Our findings described the polutant wash off character in urban road runoff, which provide a scientific basis for management of nonpoint pollution in a city and an alternative method for controlling pollution. PMID- 26841601 TI - [Research of the Stormwater Runoff and Pollution Characteristics in Rural Area of Yuhang District, Hangzhou]. AB - In order to investigate the pollution characteristics of stormwater runoff in the southern developed rural region, the runoff samples were collected from four different underlying surfaces during three storm events in Caoqiao and Pujia Tou, which are two typical villages and are located in Yuhang District of Hangzhou. The content of nutrition (nitrogen and phosphorus) and heavy metals (Mn, Cu, Zn, Ni, Cr, Cd, As, Pb) in the simples were analyzed, and the difference of EMC ( event mean concentration) and pollution load of the contaminants in the runoff on different underlying surfaces were compared. The results showed that the EMC of TSS, COD, NH4(+)-N, TP and TN were 16.19, 21.01, 0.74, 1.39 and 2.39 mg x L(-1) in the Caoqiao, respectively; as to Pujia Tou, they were 3.10, 15.69, 0.90, 0.78 and 3.58 mg x L(-1), respectively. The content of heavy metals was all lower than the national surface water quality of two type water in the runoff. Compared with the quality standards for surface water, the EMC of TP was 9 times and 3. 5 times higher and TN was 1. 8 times and 1. 2 times higher in two areas. Besides, the pollution loads of TSS and COD were the highest in farmland. PMID- 26841602 TI - [Formation and Variation of Brominated Disinfection By-products in A Combined Ultrafiltration and Reverse Osmosis Process for Seawater Desalination]. AB - The characteristics of dissolved organic matter (DOM) and brominated disinfection by-products ( Br-DBPs ) during a seawater desalination ultrafiltration (UF) combined reverse osmosis (RO) process were studied. The seawater contained high level of bromide ion (45.6-50.9 mg x L(-1)) and aromatic compounds with specific ultraviolet absorbance ( SUVA) of 3.6-6.0 L x (mg x m)(-1). The tryptophan-like aromatic protein, fulvic acid-like and soluble microbial by-product-like were the main fluorescent DOM in the seawater. After pre-chlorination of the seawater, the concentrations of DBPs was significantly increased in the influent of UF, which was dominantly the Br-DBPs. Bromoform (CHBr3) accounted for 70.48% - 91.50% of total trihalomethanes (THMs), dibromoacetic acid (Br2CHCO2H) occupied 81.14% - 100% of total haloacetic acids (HAAs) and dibromoacetonitrile (C2HBr2N) occupied 83.77% - 87.45% of total haloacetonitriles ( HANs). The removal efficiency of THMs, HAAs and HANs by the UF membrane was 36.63% - 40.39%, 73.83% - 95.38% and 100%, respectively. The RO membrane could completely remove the HAAs, while a little of the THMs was penetrated. The antiestrogenic activity in the seawater was 0.35 - 0.44 mg x L(-1), which was increased 32% - 69% after the pre chlorination. The DBPs and other bio-toxic organics which formed during the UF-RO process were finally concentrated in the UF concentrate and RO concentrate. PMID- 26841603 TI - [Effect of Natural Organic Matter and Electrolytes on the Aggregation of C60 Nanoparticles in Aquatic Systems]. AB - The ettect of natural organic matter (NOM) and electrolytes on the aggregation of G60 nanoparticles in aquatic systems was studied by using dynamic light scattering. The results showed that the concentration of C60 stable suspension prepared by toluene solvent-exchange method was about 20 mg x L(-1). The C60 nanoparticles in the suspension showed a high zeta potential and particle diameter was around 120 nm. Addition of simple electrolytes induced aggregation of C60 nanoparticles through acompressing electric double layer, which was consistent with the classic Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of colloidal stability. The critical coagulation concentration (CCC) values of MgCl2 and CaCl2 were 9.6 and 6.7 mmol x L(-1). In presence of humic acid, the addition of NaCl and MgCl2 reduced the attachment efficiency and aggregation rate of C60 and increased CCCs. Humic acid enhanced the stability of C60 in water due to steric repulsion. However, the complexation reaction between Ca2+ and humic acid caused adsorption bridging with C60, which increased the aggregation rate and led to enhanced aggregation. This was identified as the primary mechanism of such enhanced aggregation behaviour. The aggregation and dispersion of C60 in water was influenced by the characteristics of organic matters, electrolyte species and other complex factors. PMID- 26841604 TI - [Efficiency of Sediment Amendment with Zirconium-Modified Kaolin Clay to Control Phosphorus Release from Sediments in Heavily Polluted Rivers]. AB - A zirconium-modified kaolin- clay (ZrMK) was prepared and used as a sediment amendment to control the release of phosphorus (P) from sediments in heavily polluted rivers under low dissolved oxygen (DO) condition. Results showed that the ZrMK exhibited excellent adsorption performance of phosphate in water. The phosphate adsorption capacity of the ZrMK increased with the increasing of loading amount of zirconium in the ZrMK. The phosphate adsorption capacity of the ZrMK increased with the increase of the precipitated pH value from 8 to 10, remained basically unchangeable with the increase of the precipitated pH value from 10 to 11, but decreased with the increase of the precipitated pH value from 11 to 12. The phosphate equilibrium adsorption data of the ZrMK can be better described by the Langmuir isotherm model than the Freundlich isotherm model when the ZrMK was prepared with the precipitated pH value 10. Sequential extraction of P from the phosphate-adsorbed ZrMK showed that most of phosphate-P bound by the ZrMK (about 84% of total P) existed in the form of the metal oxide P (NaOH-P) and residual P (Res-P), which was unlikely to be released under hypoxia and common pH (5-9) conditions. The fluxes of phosphate-P and total P (TP) from sediments into the overlying water column were greatly reduced with the adding of ZrMK to sediments under low dissolved oxygen conditions. The ZrMK-amended sediments exhibited much higher phosphate adsorption capacity than the original sediments, and the former had much lower phosphate adsorption/desorption equilibrium concentration (EPC,) than the latter. Our findings suggest that the ZrMK can be used as an efficient sediment amendment for controlling P release from sediments in heavily polluted rivers under low dissolved oxygen conditions. PMID- 26841605 TI - [Transformation of Nitrogen Nutrients in the Urban Sewage Pipe Network]. AB - The paper focuses on the changes of nitrogen compounds in the Pipe network. A 1.2km long urban sewage simulation network with artificial water distribution was selected as the research subject. Then we analyzed and evaluated the change characteristics of nitrogen nutrients along the pipe. The results proved that ammonium chloride as the nitrogen source matrix, which was necessary for microorganisms in the Pipe to survive and proliferate. Free amino acids, combined amino acids and nucleic acid produced by metabolism were the major nitrogenous organic compounds. Among which, amino acids accounted for dissolved organic nitrogen (DON) in the majority. The characterization results of three-dimensional fluorescence spectroscopy and size exclusion chromatography showed that the characteristic fluorescence peak of organic matter in waste water was increased, and the protein ( tyrosine, tryptophan)--based fluorescence intensity gradually increased along the pipe. It was also found that small molecules of nutrients in the water were converted to complex organic molecules under the assimilation of microorganisms. PMID- 26841606 TI - [Application of Micro-aerobic Hydrolysis Acidification in the Pretreatment of Petrochemical Wastewater]. AB - Micro-aerobic hydrolysis acidification technology was applied in the reconstruction of ananaerobic hydrolysis acidification tank in a north petrochemical wastewater treatment plant. After put into operation, the monitoring results showed that the average removal rate of COD was 11.7% when influent COD was 490.3-673.2 mg x L(-1), hydraulic retention time (HRT) was 24 and the dissolved oxygen (DO) was 0.2-0.35 mg x L(-1). In addition, the BOD5/COD value was increased by 12.4%, the UV254 removal rate reached 11.2%, and the VFA concentration was increased by 23.0%. The relative molecular weight distribution (MWD) results showed that the small molecule organic matter (< 1 x 10(3)) percentage was increased from 59.5% to 82.1% and the high molecular organic matter ( > 100 x 10(3)) percentage was decreased from 31.8% to 14.0% after micro aerobic hydrolysis acidification. The aerobic biodegradation batch test showed that the degradation of petrochemical wastewater was significantly improved by the pretreatment of micro-aerobic hydrolysis acidification. The COD of influent can be degraded to 102.2 mg x L(-1) by 48h aerobic treatment while the micro aerobic hydrolysis acidification effluent COD can be degraded to 71.5 mg x L(-1) on the same condition. The effluent sulfate concentration of micro-aerobic hydrolysis acidification tank [(930.7 +/- 60.1) mg x L(-1)] was higher than that of the influent [(854.3 +/- 41.5) mg x L(-1)], indicating that sulfate reducing bacteria (SRB) was inhibited. The toxic and malodorous gases generation was reduced with the improvement of environment. PMID- 26841608 TI - [Effect of High Ammonium on Nitrogen Removal in an Partial Nitritation-ANAMMOX Process with Reflux System]. AB - The effect of influent ammonia on nitrogen transformation characteristics and microbial communities in partial nitrification-anaerobic ammonia oxidation (PN ANAMMOX) process was studied by using a series of partial nitrification and ANAMMOX process with air-lift reflux device. The results showed that when the influent ammonia concentration was increased to 700 mg x L(-1) and the nitrogen volume load was stabled at 2.8 kg x (m3 x d)(-1), the fluctuation of pH value was very small in aerobic and anaerobic zone. In the aerobic and anaerobic zone, FA concentrations were maintained at 5'mg x L(-1), 10 mg x L(-1), respectively, which did not inhibit the growth of microorganisms. Nitrite produce rate was stabled at 1.5 kg x (m3 x d)(-1) in the aerobic zone, and nitrogen removal rate was stabled at 31.49 kg x (m3 x d)(-1) in anaerobic zone, the total nitrogen removal rate was stabled at 1.67 kg x (m3 x d)(-1) in combined process. When the influent ammonia concentration was increased to 900 mg x L(-1), the FA and FNA concentration were increased in each areas, total nitrogen removal rate was decreased and stabled at 1.52 kg x- ( m3x- d( 1)'. The nitrite was accumulated in the anaerobic zone, and there was no significant inhibition of ANAMMOX bacteria. Our findings indicated that the reflux can effectively alleviate the fluctuation of pH in each area, and dilute FA concentration which is toxic to microorganisms. PMID- 26841607 TI - [Efficacy of A2/O-MBR Combined Process in Wastewater Treatment and the Characteristics of Membrane Fouling]. AB - The hydrophilic modification of PVA composite membrane was applied in the reversed A2/O-MBR process to treat wastewater, the removal efficacy of COD, NH4(+) -N, TN, TP, turbidity and performance of composite membrane were investigated. The results indicate that the average removal rates of COD, NH4(+) N and TP were higher than 90%, 95% and 80% under different reflux ratio, respectively. The reflux ratio had large impact on TN removal rate: when the reflux ratio was 100%, the removal rate was low; when the reflux ratio increases the range from 100% to 300%, the removal rate was correspondingly increased. Under the efficient interception of membrane, water turbidity was always less than 0.05NTU, and the composite film was controlled at (12 +/- 0.5) L x (m2 x h)( 1) flux, the operation was uninterrupted for 52 days without any cleaning process of the membrane, the average rate of membrane fouling is 13.22 Pa x h(-1) and the process of membrane fouling was very slow. After FTIR analysis, we confirmed that polysaccharide and protein is a main composition of organic pollutants. LB is further proved to be the main pollutants from micro acting force between the membrane and the pollutants, which is consistent with FTIR analysis. PMID- 26841609 TI - [Reductive Dechlorination of Trichloroethylene by Benzoate-Enriched Anaerobic Cultures]. AB - Gas chromatography was used to monitor the reductive dechlorination of trichloroethylene (TCE) by anaerobic enrichment cultures with benzoate as the sole carbon source. The 454 pyrosequencing technique was used to investigate the microbial community and the real-time quantitative PCR was used to quantify the gene copies of Dehalococcoides spp. (DHC). The results showed that TCE was dechlorinated to vinyl chloride along with the formation of methane in 94 days. The anaerobic enrichment cultures exhibited a high diversity, which were classified into 16 phyla, 33 classes, 52 orders, 88 families and 129 genera, while 51.2% of them belonged to unclassified group, which inferred that there were a large portion of bacteria with unknown functional in this system. Degradation of TCE was accomplished by reductive dechlorinating and other functional populations, and the DHC which carried tceA gene could be the dominant reductive dechlorinating populations in the system. PMID- 26841610 TI - [2, 4, 6-Trichlorophenol Mineralization Promoted by Anaerobic Reductive Dechlorination of Acclimated Sludge and Extracellular Respiration Dechlorination Pathway]. AB - In anaerobic conditions, the acclimation of activated sludge was studied with sodium lactate as the electron donor and 2,4,6-trichlorophenol as the electron acceptor. Metabolic characteristics of dechlorination were the focus of this study. The result showed highly efficient dechlorination on 2, 4, 6 trichlorophenol that the conversion rate reached to 100% in 9 - 24 h when initial concentrations of sodium lactate and 2,4, 6-trichlorophenol were 20 mmol x L(-1) and 40 - 80 MUmol x L(-1), respectively. The intermediate product 2,4 dichlorophenol was found in low concentration (< 4.22 MUmol x L(-1)). And 4 chlorophenol and phenol were the main products. Ortho chlorophenol (2, 4, 6 trichlorophenol, 2, 4-dichlorophenol) can be converted rapidly by acclimated sludge, while the further conversion of 4-chlorophenol and phenol was limited. The residues of anaerobic metabolism were degraded by aerobic sludge, among which 4-chlorophenol (initial concentration of 33 mol x L(-1)) removal rate was up to 100% under aerobic conditions. The acclimated bacteria can rapidly transfer Fe(III) and humus (AQDS) into reductive Fe(II) and AQH2DS which indicated that the dissimilatory iron reducing bacteria was enriched in the acclimated sludge. The electron mediator [Fe(III) and AQDS] significantly accelerated the dechlorination rate. The acclimated sludge could perform extracellular respiration dechlorination with electron mediators. PMID- 26841611 TI - [Short or Long-Term Influence of Phenol on Nitrogen Removal Efficiency of ANAMMOX Sludge]. AB - The effects of phenol concentration on nitrogen removal efficiency in ANAMMOX sludge were studied in short or long-term. The nitrogen removal rate decreased rapidly with the increase of concentration of phenol in short-term. When the phenol concentration was above 600 mg x L(-1), the removal rate of NH4(+) -N was lower than 6% and the removal rate of TN was only about 10%. The long-term experimental results showed when the phenol concentration was below 100 mg x L( 1), the removal rate of NH4(+) -N can reach 99%, which indicated that ANAMMOX bacteria have a process of adaptation to the low concentration of phenol. However, when the phenol concentration was above 400 mg x L(-1), the removal rate of NH4(+) -N and TN was only 23.59% and 50.3%, the activity in sludge was significantly inhibited which was similarly to the short-term and the activity of denitrifying bacteria was significantly higher than ANAMMOX bacteria. As an organic carbon source, phenol can activated denitrification reaction and finally plays a dominant role in the system. However, the high concentration of phenol (1 000 mg x L(-1)) also has an inhibitory effect on denitrification bacteria. Half inhibitory concentration (IC50) of phenol to ANAMMOX activity was 71.57 mg x L( 1) by fitting. After 18 days' recovery, the stoichiometric ratios of nitrogen were changed, although the NH4(+) -N was basicly removed. The ratio of removed NH4(+) -N, reomved NO2(-) -N and produced NO3(-) -N was 1: 0.86: 0.2. Our results showed that the concentration of phenol should be controlled within a reasonable range, so that the reactor can achieve simultaneous removal of phenol and nitrogen. PMID- 26841612 TI - [Process Optimization of Aerobic Granular Sludge Continuous-Flow System for the Treatment of Low COD/N Ratio Sewage]. AB - The mature aerobic granular sludge (AGS) was inoculated in a continuous-flow joint constructor reactor to treat low chemical oxygen demand/nitrogen (COD/N) ratio sewage. The effects of aeration intensity and hydraulic retention time (HRT) on the denitrification and phosphorus removal efficiencies and the granular sludge stabilization were investigated. When the aeration intensity was 300 mL x min(-1) (superficial air upflow velocity of 1.2 cm x s(-1)) and the HRT was 7.5 h, the average removal efficiencies of COD, TN and TP were 76.34%, 51.23% and 53.70%, respectively. The mixed liquor suspended solids (MLSS) was only about 2 000 mg x L(-1), the sludge volume index ( SVI) was below 50 mL x g(-1), and the AGS exhibited complete forms and good settling performances. Additionally, the low COD/N ratios sewage could promote the production of extracellular polymeric substances (EPS) of AGS, and the PN proteins in EPS played a pivotal role in the maintenance of AGS stabilization. PMID- 26841613 TI - [Long-Term Inhibition of FNA on Aerobic Phosphate Uptake and Variation of Phosphorus Uptake Properties of the Sludge]. AB - An alternating anaerobic/oxic ( An/O) sequencing batch reactor (SBR) was employed to investigate the long-term inhibitory effect of free nitrous acid (FNA) on aerobic phosphorus uptake performance and variation of phosphorus uptake properties of the sludge by adding nitrite. The reactor was started up under the condition of 21-23 degrees C. The results showed that FNA had no impact on phosphate release and uptake capacities of the sludge. However, the specific phosphate release/uptake rates was found to be higher. As FNA concentration (measure by HNO2-N) was lower than 0.53 x 10(-3) mg x L(-1), phosphorus removal efficiency of the system was higher than 96.9%. When the FNA concentration was increased to 0.99 x 10(-3) mg x L(-1), 1.46 x 10(-3) mg x L(-1) and 1.94 x 10(-3) mg x L(-1), the phosphorus removal performance deteriorated rapidly. The phosphorus removal efficiency was recovered to 64.42%, 67.33% and 44.14% after 50, 12 and 30 days, respectively, which implied the deterioration of phosphorus removal performance caused by FNA inhibition could be recovered and long-term acclimation could shorten the recovery process. Notably, increasing nitrite consumption appeared during aerobic phase with the concentration of FNA below 1.46 x 10(-3) mg x L(-1). It was also observed that the phosphorus uptake properties of the sludge varied after long-term inhibition. Nitrate and nitrite type anoxic phosphorus uptake capacity was increased by 3.35 and 3.86 times, respectively, suggesting long-term dosing FNA may facilitate the denitrifying of polyphosphate in organisms utilizing nitrite as electron acceptor. Moreover, long term acclimation favored sludge settling. PMID- 26841614 TI - [Performance and Factors Analysis of Sludge Dewatering in Different Wastewater Treatment Processes]. AB - Sludge dewatering is one of the keys for sludge disposal and treatment of municipal wastewater treatment plants. In this study, the sludge dewaterability, flocculant consumption and costs of sludge dewatering for different wastewater treatment processes including A2/O and A2/O-MBR processes were analyzed, as well as the factors of sludge dewatering were analyzed by redundancy analysis (RDA) method, based on the data of one municipal wastewater treatment plant of Beijing in 2013. Results showed that both sludge dewaterability and flocculant consumption presented the seasonal variation, which means sludge dewatering was harder and coupled with higher flocculant consumption in the winter. Although the lower moisture content of dewatered sludge was obtained in the A2/O-MBR process (81.92% +/- 1.64% ) compared with that in the A2/O process (82.56% +/- 1.35%), the consumptions of flocculant [ (8.70 +/- 7.25) kg x t(-1) DS] and electric energy (331.82 kW x h x t(-1) DS) in the A2/O-MBR process were higher than those in the A2/O process [(7.42 +/- 2.96) kg x t(-1) DS, 121.57 kW x h x t(-1) DS for flocculant consumption and electric energy respectively], resulting in higher operation costs (RMB 204.76 yuan x t(-1) DS of flocculant consumption and RMB 231.61 yuan x t(-1) DS of energy consumption for the A2/O-MBR, RMB 175.00 yuan x t(-1) DS of flocculant consumption and RMB 84.86 yuan x t(-1) DS of energy consumption for the A2/O, respectively). Results of RDA showed that the seasonal variation of sludge dewaterability mainly depended on the content of organic matter in sludge which was related to the seasonal factors such as temperature, and was also impacted by the operating parameters such as SRT in wastewater treatment. PMID- 26841615 TI - [Effect of Residual Hydrogen Peroxide on Hydrolysis Acidification of Sludge Pretreated by Microwave -H2O2-Alkaline Process]. AB - Previous studies have found that in the hydrolysis acidification process, sludge after microwave -H2O2-alkaline (MW-H2O2-OH, pH = 10) pretreatment had an acid production lag due to the residual hydrogen peroxide. In this study, effects of residual hydrogen peroxide after MW-H2O2-OH (pH = 10 or pH = 11) pretreatment on the sludge hydrolysis acidification were investigated through batch experiments. Our results showed that catalase had a higher catalytic efficiency than manganese dioxide for hydrogen peroxide, which could completely degraded hydrogen peroxide within 10 min. During the 8 d of hydrolysis acidification time, both SCOD concentrations and the total VFAs concentrations of four groups were firstly increased and then decreased. The optimized hydrolysis times were 0.5 d for four groups, and the optimized hydrolysis acidification times were 3 d for MW-H2O2-OH (pH = 10) group, MW-H2O2-OH (pH = 10) + catalase group and MW-H2O2-OH (pH = 11) + catalase group. The optimized hydrolysis acidification time for MW-H2O2-OH (pH = 11) group was 4 d. Residual hydrogen peroxide inhibited acid production for sludge after MW-H2O2-OH (pH = 10) pretreatment, resulting in a lag in acidification stage. Compared with MW-H2O2-OH ( pH = 10) pretreatment, MW-H2O2-OH (pH = 11 ) pretreatment released more SCOD by 19.29% and more organic matters, which resulted in the increase of total VFAs production significantly by 84.80% at 5 d of hydrolysis acidification time and MW-H2O2-OH (pH = 11) group could shorten the lag time slightly. Dosing catalase (100 mg x -L(-1)) after the MW H2O2-OH (pH = 10 or pH = 11) pretreatment not only significantly shortened the lag time (0.5 d) in acidification stage, but also produced more total VFAs by 23.61% and 50.12% in the MW-H2O2-OH (pH = 10) + catalase group and MW-H2O2-OH (pH = 11) + catalase group, compared with MW-H2O2-OH (pH = 10) group at 3d of hydrolysis acidification time. For MW-H2O2-OH (pH = 10) group, MW-H2O2-OH (pH = 10) + catalase group and MW-H2O2-OH(pH = 11) + catalase group, the dominant VFAs were acetic, iso-valeric and n-butyric acids. For MW-H2O2-OH (pH = 11) group, the dominant VFAs were acetic, propionic and iso-valeric acids. In the optimized hydrolysis acidification time for each group, percentages of the three main acids accounted for more than 75% of total VFAs, and percentages of acetic acid accounted for more than 41% of total VFAs. PMID- 26841616 TI - [Vertical Distribution Characteristics of Typical Forest Soil Organic Nitrogen in Dawei Mountain]. AB - To clarify altitudinal gradient of subtropical forest soil total nitrogen and organic nitrogen, soil samples were collected per 10 cm on soil profile (0-100 cm) in Dawei Mountain, researched the variation of soil organic nitrogen and correlation with soil physical and chemical properties. The results showed that: (1) Total nitrogen, acid hydrolysable organic nitrogen and soluble organic nitrogen decreased with the increase of depth, content of each component in mountain granite yellow-brown soils was much higher affected by altitude; (2) The average percentage of soil organic nitrogen to total nitrogen was 97.39% +/- 1.17%, and soil acid hydrolysable organic nitrogen was 64.38% +/- 10.68%, each component decreased with the increase of soil depth; (3) Soil soluble organic nitrogen content was 9.92- 23.45 mg x kg(-1), free amino acids (1.62 - 12.02 mg x kg(-1)) accounted for about 27.36% +/- 9.95% of soluble organic nitrogen; (4) Soil acid hydrolysable organic nitrogen and soluble organic nitrogen were significantly positively correlated with total nitrogen, total soluble nitrogen and inorganic nitrogen (P < 0.05), were highly significantly correlated with soil bulk density, organic carbon, and total phosphorus (P < 0.01). Organic nitrogen was the main body of soil nitrogen in typical subtropical forest, each component showed a downward trend increase with soil depth affected by altitude and soil physical and chemical properties. There was a close conversion relationship between soil organic nitrogen and other nitrogen forms, the characteristics of soil organic nitrogen will have profound impact on nitrogen cycling of forest ecological system. PMID- 26841617 TI - [Effects of Different Land Uses on Soil Active Organic Carbon and Nitrogen Fractions in Jinyun Mountain]. AB - In this paper, we take Jinyun Mountain where located in Beibei district of Chongqing as the research object and explore the effect of different ways of land use on soil active organic carbon, nitrogen components by collecting the soil samples from 0 to 60 cm depth in subtropical evergreen broad-leaved forest (hereinafter referred to as the forest), abandoned land, orchard, farmland and measuring the content of MBC, MBN, DOC and DON. The research results show that the contents of soil MBC, MBN, DOC, DON are reduced with the increase of soil depth in four types of land using soils. Variance analysis of the single factor shows that four kinds of land uses have no significant difference in the contents of MBC, MBN and DON, but the DOC content of the abandoned land is significantly higher than that of other three kinds. It shows that the different ways of land use have no obvious effects on soil MBC, MBN and DON but the abandonment of slope cropland can significantly increase the content of soil DOC. There is no significant difference among the distribution ratio of MBN, DOC, DON in forest, abandoned land, orchard and farmland within the soil from 0 to 60 cm, but the distribution ratio of slope MBC is significantly higher than that of other three kinds. It means farmland soil organic carbon has a higher biological activity, this could due to the application of green manure, farmland manure and other organic fertilizers. Under different land utilizations, DOC/DON is the highest, MBC/MBN is the second, and SOC/TN is the lowest. It means the biological solidification of dissolved organic matter is the strongest, and the mineralization of soil organic matter is the most obvious. Under the four kinds of land uses, there are the lowest ratios in SOC/TN, MBC/MBN and DOC/DON in the farmland. And all the ratios are less than 20, which suggest that the mineralization of farmland soil organic matter is stronger and it's easy to cause the loss of soil carbon. PMID- 26841618 TI - [Control of Soil Nutrient Loss of Typical Reforestation Patterns Along the Three Gorges Reservoir Area]. AB - Annual soil nutrient loss characteristics on typical reforestation patterns in watershed along the Three Gorges Reservoir Area were studied based on runoff plot experiment. Runoff and sediment nutrition content from May to October 2014 of typical reforestation patterns including garden plot (tea garden), forest land (Chinese chestnut) and the original slope farmland were determined and then analyzed. The results showed that: (1) After the Returning Farmland to Forest Project the quantity of annual soil nutrient (nitrogen and phosphorus, the sum of them in sediment and runoff) loss decreased. The output of total nitrogen (TN) was in the order of slope farmland (2 444.27 g x hm(-2)) > tea garden (998.70 g x hm(-2)) > Chinese chestnut forest (532.61 g x hm(-2)), and for total phosphorus (TP) loss was slope farmland (1 690.48 g x hm(-2)) > tea garden (488.06 g x hm( 2)) > Chinese chestnut forest (129.00 g x hm(-2)) . Compared with slope farmland, the load of TN and TP output of reforestation patterns decreased 68.68% and 81.75%, respectively. (2) Compared with slope farmland, available nitrogen loss decreased in reforestation patterns. Total nitrate nitrogen (NO3(-)-N) loss ranked in the order of slope farmland (113.79 g x hm(-2)) > tea garden (73.75 g x hm(-2)) > Chinese chestnut forest (56.06 g x hm(-2)) The largest amount of ammonium nitrogen (NH4(+)-N) was found in tea garden (69.34 g x hm(-2)), then in farmland (52.45 g x hm(-2)), and the least in Chinese chestnut forest (47.23 g x hm(-2)). (3) The main route of NO3(-)-N and NH4(+)-N loss was both through runoff, the quantity of NO3(-)-N and NH4(+)-N output in which accounted for 91.4% and 92.2% of the total, respectively. The quantity of TN and TP in sediment accounted for 86.6% and 98.4% of the total. TN and TP loss showed an extremely significant correlation with sediments, which showed that sediment output was the main approach of TN and TP loss. PMID- 26841619 TI - [Effects of Slope Position and Soil Horizon on Soil Microbial Biomass and Abundance in Karst Primary Forest of Southwest China]. AB - To explore the effects of slope position and soil horizon on soil microbial biomass and abundance, chloroform fumigation extraction methods and real-time fluorescence-based quantitative PCR (Real-time PCR) were adopted to quantify the changes of soil microbial biomass C, N and abundance of bacteria and fungi, respectively. Soil samples were harvested from three horizons along profile, i. e., leaching horizon (A, 0-10 cm), transitional horizon (AB, 30-50 cm) and alluvial horizon (B, 70-100 cm), which were collected from the upper, middle and lower slope positions of a karst primary forest ecosystem. The results showed that slope position, soil horizon and their interaction significantly influenced the soil microbial biomass and abundance (P < 0.05). Different from A horizon, where SMBC was greater in lower than in upper slope position (P < 0.05), SMBC in AB and B horizons were highest in middle slope position. Similarly, SMBN was greater in lower than in upper slope position for A, AB and B horizons. Besides soil bacterial abundance in B horizon and fungal abundance in AB layer, the middle slope position had the highest value for all the three soil horizons (P < 0.05). Stepwise regression analysis showed that soil organic carbon, available nitrogen and pH were the key factors responsible for SMBC and SMBN variation, respectively, while the important factors responsible for the variation of bacteria abundance were available nitrogen and available phosphorus, and that for fungi abundance variation were available potassium. PMID- 26841620 TI - [Effects of Different Plantation Type on the Abundance and Diversity of Soil Microbes in Subtropical Red Soils]. AB - Soil microbe plays an important role in carbon cycling, however, the effect of land use on soil microbe remain unclear. In present study, soil samples were collected from a long-term field experiment (Pantang Agroecosystem) in subtropical China (established in 1989), including paddy-rice (PR), upland-crop (UC), and paddy rice-upland crop rotation (PU) on soil bacterial (bacteria and Archaea) community structures. The effects of long-term different land uses were determined using terminal restriction fragment length polymorphism (T-RFLP) and quantitative PCR (RT-PCR) of the 16S rRNA gene. The abundance of soil microbial 16S rRNA genes ranged from 2.5 x 10(9)-1.5 x 10(10) copies x g(-1) dry soil. Compared with the PR, UP and UC led to a significant reduction in 16S rRNA genes abundance (P < 0.05). The soil microbial communities were dominated by bacteria such as Proteobacteria (76 and 90 and 327 bp; relative abundance of 47% - 53%) and Chloroflexi (65 bp; relative abundance of 10% - 12%). RDA statistical analyses demonstrated that there were significant differences in the microbial community composition in PR, UC, and PU treated soils. Soil organic carbon and total nitrogen content were the most highly statistically significant factors which positively influenced the soil microbial population. Taken together, our findings prove the long-term different land uses significantly influence the microbial diversity and community structure. The rice planting is an effective way of sustainable utilization of subtropical red soil, and it is more advantageous to the accumulation of soil organic matter, soil fertility and microbial diversity. PMID- 26841621 TI - [Accumulation of Mercury in Soil-maize System of Non-ferrous Metals Smelting Area and Its Related Risk Assessment]. AB - Soil heavy metal pollution, especially the mercury pollution, has been widespread concern in non-ferrous metallurgical area. This study focused on the content, distribution and pollution status of Hg in maize soil of Huludao city. Meanwhile, Hg contents in the various organs of maize were analyzed. Hg concentration in soil ranged from 0.25 to 3.49 mg x kg(-1) with the average content of 1.78 mg x kg(-1), which was 48 times as high as the background value of Liaoning soil. Around 2-3m range of zinc plant, the pattern of spatial distribution showed that the content of Hg was gradually increased with the increase of the distance to Huludao zinc plant. The result of geoaccumulation index reflected that Hg pollution is up to moderate pollution level on the whole. 54. 6% of the total sample were belonged to the serious pollution level. The potential ecological risk index of Hakanson was applied to assess the ecological risk of Hg. The target hazard quotient method (THQ) was used to assess the health risk for human, the results revealed that there was no significant health risk by consumption corn. Mercury is very difficult to transport in soil-maize system, and there is no obvious health risks to adults. But the risk coefficient of children, which is up to 0.056. is much higher than adults. PMID- 26841622 TI - [Effects of Different Modifier Concentrations on Lead-Zinc Tolerance, Subcellular Distribution and Chemical Forms for Four Kinds of Woody Plants]. AB - Four kinds of lead-zinc tolerant woody plants: Nerium oleander, Koelreuteria paniculata, Paulownia and Boehmeria were used as materials to estimate their enrichment and transferable capacity of lead (Pb) and zinc (Zn) and analyze the subcellular distribution and chemical speciation of Zn and Ph in different parts of plants, under different modifier concentrations (CK group: 100% lead-zinc slag plus a small amount of phosphate fertilizer, improved one: 85% of lead-zinc slag +/- 10% peat +/- 5% bacterial manure plus a small amount of phosphate fertilizer, improved two: 75% lead-zinc slag +/- 20% peat +/- 5% bacterial manure +/- a small amount of phosphate). Results showed that: (1) The content of Pb, Zn in matrix after planting four kinds of plants was lower than before, no significant difference between improved one and improved two of Nerium oleander and Boehmeria was found, but improved two was better than improved one of Paulownia, while improved one was better than improved two of Koelreuteria paniculata; Four plants had relatively low aboveground enrichment coefficient of Pb and Zn, but had a high transfer coefficient, showed that the appropriate modifier concentration was able to improve the Pb and Zn enrichment and transfer ability of plants. (2) In subcellular distribution, most of Pb and Zn were distributed in plant cell wall components and soluble components while the distribution in cell organelles such as mitochondria, chloroplasts and nucleus component were less. Compared with CK group, two improved group made soluble components of the cell walls of Pb fixation and retention of zinc role in the enhancement. (3) As for the chemical forms of Pb and Zn in plants, the main chemical forms of Pb were hydrochloric acid, sodium chloride and ethanol extractable forms, while other chemical form contents were few, the main chemical forms of Zn were different based on plant type. Compared with CK group, the proportion of the active Pb chemical form in different plant parts decreased in two improved groups, while the proportion of strong activity chemical forms increased; two improved groups led strong activity Zn chemical form of root increased, while strong activity Zn chemical form of aboveground decreased. PMID- 26841623 TI - [Isolation, Purification and Identification of Antialgal Activity Substances of Ethyl Acetate Extracts from the Submerged Macrophytes Potamogeton crispus]. AB - Previous studies showed that ethyl acetate extracts from the submerged macrophytes Potamogeton crispus can significantly inhibit the growth of Karenia mikimitoi. Further, two antialgal activity compounds (1-2) were successfully isolated from this submerged macrophytes through a combination of silica gel column chromagraphy and repeated preparative thin-layer chromatography in this paper. These two antialgal activity compounds exhibited antialgal active against Karenia mikimitoi. Furthermore, their structure were identified on the basis of spectroscopic data: one flavonid named Trichodermatides B, and one alkaloid named 2-methylheptylisonicotinate. These two compounds were for the first time isolated from both Potamogeton crispus and submerged macrophytes. PMID- 26841624 TI - [Distribution Characteristics and Potential Risk of CBs in Aquatic Organisms from Typical Epidemic Areas of Schistosomiasis Prevalence]. AB - Eleven mollusca samples and 32 fish samples were collected from typical epidemic areas of schistosomiasis prevalence. The contents of 12 CB congeners in aquatic organism samples were measured using the GC/MS technique. The results indicated that 1,3-DIC, 1,4-DIC, 1,2-DIC and HCB were the most predominant CB congeners in the samples from the studying area. The geometric average of CBs in muscle of mollusca was 11 947 ng x g(-1) lipid weight. The summarized concentration of CBs in fish muscle ranged from 1 851 to 8 159 ng x g(-1) lipid weight. The highest concentration of CBs sum was detected in the catfish, while the lowest one was found in the crucian carp. The concentrations of CBs in fish samples were much higher than those reported in other countries, while in mollusca samples were at the same level. The estimated cumulative cancerigenic risks for the local residents consumed the aquatic organisms from the studying area were 1.49 x 10( 7) and 3.73-21.1 x 10(-7), respectively for mollusca and fish, both of which were acceptable. PMID- 26841625 TI - [Application of Whole-cell Biosensor ADP1_pWHlux for Acute Toxicity Detection in Water Environment]. AB - A whole-cell biosensor acinetobacter ADP1_pWHlux was constructed by genetic engineering for detecting acute toxicity, so as to overcome the harsh application conditions when detecting acute toxicity using natural luminescent bacteria or whole-cell biosensor constructed by model microorganisms as the host cell. Detection methods, detection sensitivity and detection range of acinetobacter ADP1_pWHlux were studied. The results showed that the luminescence of ADP1_pWHlux was inhibited by acute poison, poison dose and inhibition of luminescence exhibit dose-response relationship. ADPL_pWHlux was respond to 4 mg x L(-1) HgCl2 within 5 min. The detection limit for HgCl2 was 0.04 mg x L(-1). The detectable effects for indicators of Be2+, Ba2+, Cu2+, Ni2+ in standards for drinking water quality were obvious. The detection range of Be2+, Ba2+, Cu2+ were 0.025-250 mg x L(-1), the detection range of Ni2+, was 0.0025-250 mg x L(-1), the detection limit of Pb2+, BrO3(-) , ClO2(-) were 0.002 5 mg x L(-1), the detection limit of ClO3(-) was 0.025 mg x L(-1). The whole-cell biosensor ADPl_pWHlux detection method has been applied to evaluate acute toxicity in water environment of Qinghe river in Beijing, indicating the established method can be used to detect contaminated water samples. PMID- 26841626 TI - [Application of Rainbow Trout CYP1 Gene Expression Patterns in Gill and Liver for Haihe River Bio-monitoring]. AB - CYP1 subfamily genes in gills and liver of rainbow trout as biomarkers were studied to establish methods for quantitative mRNA expression analysis of these genes and to determine their expression pattern. Fish caged in various waters in the Haihe River (Tianjin) were analyzed. The mRNA expression patterns observed in Machangjian River and estuary site of Haihe River were markedly similar but at different levels, reflecting that those sites shared the similar pollution components but with different local pollution load. CYP1C1 and 1C3 were only induced at Gegu site and estuary site of Haihe River, indicating different types of CYP1 agonists in Machangjian River. Response patterns of multiple CYP1 genes in gills and liver could be applied in the monitoring strategy. The response patterns of CYP1 genes could be used for better understanding the relationship between complex mixtures of pollutants and biological response of organisms in aquatic environments. PMID- 26841628 TI - [Acute Toxicity of Coptis chinensis Rhizome Extracts to Daphnia carinata]. AB - Coptis chinensis rhizome and preparations were widely used for the treatment of fish diseases in aquaculture. the acute toxicological effect of CRE on lethal, movement and phototaxis was studied on Daphnia carinata monoclone as a test animal in the present experiment. The results showed that CRE was acute toxic to this animal and alkaloids berberine concentrations in CRE changed in the following sequence: half lethal > half inhibitory > limitable, which led to a significant change in phototaxis index of Daphnia carinata. The concentration of CRE for the significant change in phototaxis index was 4.27 mg x L(-1), which was lower than the concentration in water to cure the fish diseases and this conclusion indicated an ecological risk of this antibiotic to Daphnia carinata in aquaculture. In addition, the concentration of CRE in phototaxis index was changed from 30.62 times at 48th hour to 36.51 times at 24th hour that were lower than half lethal concentration. Detecting phototaxis index was easy and only 3 hours was required, so utilizing the quickly change of Daphnia carinata phototaxis can be an effective method to monitor the toxicity effect of CRE on Daphnia carinata. The abuse of rhizome or preparations in aquaculture might destroy the aquatic food chain, resulting in an imbalance of aquatic ecosystems. PMID- 26841627 TI - [Toxic Effect of Nano-ZnO in Liver of Zebrafish]. AB - For acute toxicity test, zebrafish were respectively exposed to the different concentrations of nano-ZnO (0, 0.05, 0.1, 5, 10, 25, 50 mg x L(-1)) for 4, 24 and 96 h. The superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT) in the liver of zebrafish were studied, and the relative expression of Bcl-2, Bax, p53 and MDM2 in liver were also determined. Anatomical structure of the zebrafish liver was determined after exposure to nano-ZnO for 7, 15 and 30 d. Compared with the control group, the liver of the experimental groups showed obvious difference in following aspects: (1) oedema, cytoplastic vacuolation, and pyknotic nucleus were observed; (2) the number of hepatic macrophages deposited and the sinus clearance were increased; (3) the MDA contents and the activity of SOD were increased; (4) however, the activity of CAT was decreased; (5) the mRNA expression level of genes Bax/Bcl-2 ratio and p53 of stressed groups were up regulated; the mRNA expression level of gene MDM2 down-regulation can be observed in the low concentration groups while the mRNA expression level of gene MDM2 was up-regulated in the high concentration groups. The results suggested that, the oxidative damage of nano-ZnO to the zebrafish liver was caused by the increase of oxidative stress, which made the change of antioxidant enzyme activity, induced the expression of cell apoptosis genetic and cell apoptosis, and caused the change of organizational structure of liver. PMID- 26841630 TI - [Application of Stir Bar Sorptive Extraction and Gas Chromatograph Mass Spectrometer to the Phthalic Acid Esters Analysis in Seawater]. AB - For the determination of trace amounts of phthalic acid esters (PAEs) in complex seawater matrix, a stir bar sorptive extraction gas chromatography mass spectrometry (SBSE-GC-MS) method was established. Dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP), butyl benzyl phthalate (BBP), dibutyl phthalate (2-ethylhexyl) phthalate (DEHP) and dioctyl phthalate (DOP) were selected as study objects. The effects of extraction time, amount of methanol, amount of sodium chloride, desorption time and desorption solvent were optimized. The method of SBSE-GC-MS was validated through recoveries and relative standard deviation. The optimal extraction time was 2 h. The optimal methanol content was 10%. The optimal sodium chloride content was 5% . The optimal desorption time was 50 min. The optimal desorption solvent was the mixture of methanol to acetonitrile (4:1, volume: volume). The linear relationship between the peak area and the concentration of PAEs was relevant. The correlation coefficients were greater than 0.997. The detection limits were between 0.25 and 174.42 ng x L(-1). The recoveries of different concentrations were between 56.97% and 124.22% . The relative standard deviations were between 0.41% and 14.39%. On the basis of the method, several estuaries water sample of Jiaozhou Bay were detected. DEP was detected in all samples, and the concentration of BBP, DEHP and DOP were much higher than the rest. PMID- 26841629 TI - [Adsorption-desorption Characteristics of Fermented Rice Husk for Ferrous and Sulfur Ions]. AB - To understand the potential of rice husk to fix Fe2+ and S2- ions, the sorption of Fe2+ and S2- by fermented rice husk was studied by using batch incubation experiments in the present study. The effects of adsorption time, Fe2+ and S2- concentration, pH, the temperature and ionic strength in adsorption reaction solution on the sorption were investigated. Therefore, the stability of Fe2+ and S2- adsorbed by fermented rice husk was further validated by desorption experiments performed under similar conditions as adsorption. The results showed that, the adsorption kinetics of Fe2+ (r = 0.912 1) and S2- (r = 0.901 1) by fermented rice husk fits the Elovich kinetics equation, and Freundlich isotherm model could simulate the isotherm adsorption processes of Fe2+ (R2 = 0.965 1) and S2- (R2 = 0.936 6) on fermented rice husk was better than other models. The adsorption processes on fermented rice husk were non- preferential adsorption for Fe2+ and S2, while the adsorption process of Fe2+ on fermented rice husk was spontaneous reaction and the adsorption process of S2- was non-spontaneous reaction. The adsorption processes of Fe2+ and S2- on fermented rice husk were endothermic process since high temperature could benefit to the adsorption. The adsorption mechanism of Fe2+ on fermented rice husk was mainly controlled by coordination adsorption, the adsorption mechanism of S2- on fermented rice husk was mainly controlled by ligand exchange adsorption. The adsorption processes of Fe2+ and S2- on fermented rice husk showed greater pH adaptability which ranged from 1.50 to 11.50. With the increasing of ionic strength, the amount of adsorbed Fe2+ on fermented rice husk wasincreased in some extent, the amount of adsorbed S2- on fermented rice husk was slightly decreased, which further proved the adsorption of Fe2+ was major in inner sphere complexation and the adsorption of S2- was major in outer complexation. The desorption rates of Fe2+ and S2- which was adsorbed by fermented rice husk were lower in different pH or ionic strength conditions, the desorption rates were all below 10 percentage which proved that the adsorption stabilities of Fe2+ and S2- on fermented rice husk were superior. The above results indicated that, the adsorption abilities to Fe2+ and S2- on fermented rice husk were better and had greater environmental adaptability. The Fe2+ and S2- adsorbed by fermented rice husk showed higher stability, and were not easy to release again. PMID- 26841631 TI - [Experimental Conditions and Reliability Analysis of Results of COD components]. AB - The present study attempts to use SF( OUR(max)/OUR(en)) instead of S(0)/X(0) as an index of optimal initial conditions for determination of COD components by means of respirometry, thereby simplifying the measuring process and the operation can be automated. Further, the ratio of COD consumed by the growth of biomass can be used for the reliability assessment of results. Experimental results show that, experimental conditions for obtaining good results as follows: (1) for samples that composed of a large amount of easily biodegradable components (e. g., synthetic wastewater made by sodium acetate), SF should be in the range of 2.8 to 5.3, and the ratio of COD consumed by growth of biomass should be less than 30%; (2) for samples that composed of both readily biodegradable and slowly biodegradable components (i. e., typical domestic wastewater), SF should be in the range of 5.8 to 6.4, and the ratio of COD consumed by growth of biomass should be less than 30%; (3) and for samples that composed of a large amount of slowly biodegradable industrial wastewater (i. e., landfill leachate), SF should be 15 or less, and the ratio of COD consumed by growth of biomass should be approximately 40%. Therefore, when respirometry is used for the determination of COD components, the optimal conditions in terms of SF increase with the complexity of carbon source. PMID- 26841632 TI - [Method for Simultaneous Determination of 11 Veterinary Antibiotics in Piggery Wastewater and Sludge and Its Application in Biological Treatment]. AB - In order to determine eleven commonly used veterinary antibiotics (including four tetracyclines, two sulfonamides, three quinolones and two macrolides) in piggery wastewater and activated sludge in the Yangtze River Delta region, the conditions of solid phase extraction and high performance liquid chromatography-tandem mass spectrometry were optimized. The recovery rate and relative standard deviations of the method were confirmed as 73% - 105.2%, 3.1% - 10.2% for piggery wastewater (n = 3) and 57.4% - 104.6%, 1.9% - 10.9% (n = 3) respectively for the activated sludge. Removal of antibiotics was then studied in a membrane bioreactor. The results showed that antibiotics of both tetracycline and sulfonamide species took a large portion in the wastewater, while tetracycline species were the dominant in the sludge. Tetracycline species in the wastewater were removed by 85.2%, mainly through biodegradation (51.9%) and secondly by sludge adsorption (33.2%). By comparison, sulfonamide species was removed by 95.8%, almost all through biodegradation while little by sludge adsorption. Flask tests suggested that the accumulated antibiotics in the sludge give no significant influence on the microbial removal of organics and ammonium. PMID- 26841633 TI - [Research Progress in Technology of Using Soil Micro-organisms to Generate Electricity and Its Potential Applications]. AB - Microbial fuel cells ( microbial fuel cells, MFCs) are devices in which micro organisms convert chemical energy into electrical power. Soil has electrogenic bacteria and organic substrates, thus can generate electrical current in MFCs. Soil MFCs can be operated and applied to real-time and continuously monitor soil pollution, remove soil pollutants and to reduce methane emitted from flooded rice paddy, without energy consumption and the application of chemical reagents to the soil. Instead, the operation of soil MFCs generates small amount of electrical power. Therefore, soil MFCs are useful in the development of environment-friendly technology for monitoring and remediating soil pollution, which have potential value for applications in the domain of environmental science and engineering. However, much of advanced technology hasn't been applied into soil MFCs since the studies on soil MFCs was not started until recently. This paper summarized the research progress in related to soil MFCs combining with the frontier of MFCs technology, and brought forward the possible direction in studies on soil MFCs. PMID- 26841634 TI - Microbicide Development Hinges on New Products Administered in New Ways. PMID- 26841635 TI - AN INTERVIEW WITH Francoise Barre-Sinoussi. PMID- 26841636 TI - WHEN EBOLA RETURNS, Will the World be Ready? PMID- 26841637 TI - Boot Camp Emphasizes Industry-Style Approach to HIV Vaccine Development. PMID- 26841639 TI - Primary Dysmenorrhea in Adolescents: Prevalence, Impact and Recent Knowledge. AB - BACKGROUND AND OBJECTIVES: Dysmenorrhea is commonly categorized into two types; primary and secondary. Primary dysmenorrhea (PD) is the focus of this review. PD is defined as painful menses with cramping sensation in the lower abdomen that is often accompanied by other symptoms, such as sweating, headache, nausea, vomiting, diarrhea, and tremulousness. All these symptoms occur just before or during the menses in women with normal pelvic anatomy. In adolescents the prevalence of PD varies between 16% and 93%, with severe pain perceived in 2% to 29% of the studied girls. Several studies suggest that severe menstrual pain is associated with absenteeism from school or work and limitation of other daily activities. One-third to one-half of females with PD are missing school or work at least once per cycle, and more frequently in 5% to 14% of them. The wide variation in the prevalence rates may be attributed to the use of selected groups of subjects. Many risk factors are associated with increased severity of dysmenorrhea including earlier age at menarche, long menstrual periods, heavy menstrual flow, smoking and positive family history. Young women using oral contraceptive pills (OCP) report less severe dysmenorrhea. The considerably high prevalence of dysmenorrhea among adolescents verified that this condition is a significant public health problem that requires great attention. SUMMARY OF MAIN RESULTS: Many methodological problems are encountered during quantifying and grading severity of pain related to dysmenorrhea. Quantifying and assessment tools depend on women's self-reporting with potential bias. There is a scarcity of longitudinal studies on the natural history of dysmenorrhea as well as the possible effects of many modifiable risk factors. In addition, the duration of follow-up in the available studies is relatively short. Therefore, several aspects are still open for research. Medical treatment for dysmenorrhea includes anti-inflammatory drugs (NSAIDs), OCP or surgical intervention. The efficacy of conventional treatments using NSAIDs and OCP is high. However, failure rate may reach up to 20% to 25%, besides the occurrence of drug-associated adverse effects. Only 6% of adolescents receive medical advice to treat dysmenorrhea while 70% practice self-management. Unfortunately, some girls even abuse these medications (non-therapeutic high doses) for quick pain relief. The persistence of dysmenorrhea despite the use of OCP and/or NSAIDs drugs is a strong indicator of an organic pelvic disease. This condition mandates an appropriate referral to a gynecologist with proper laparoscopic diagnosis of endometriosis and/or other pelvic diseases. CONCLUSIONS: Dysmenorrhea is an important health problem for adolescents, school and occupational as well as practitioners that adversely affects the daily activities and quality of life for adolescent women. The accurate prevalence of dysmenorrhea is difficult to establish due to the variety of diagnostic criteria and the subjective nature of the symptoms. In adolescents, moderate to severe dysmenorrhea that affects lifestyle and does not respond to medical treatment requires professional attention and proper diagnosis of possible underlying pelvic disease. Therefore, adolescent care providers should be more knowledgeable and actively involved in the care of dysmenorrhea. PMID- 26841640 TI - Insulin-Like Growth Factor Binding Proteins--an Update. AB - The insulin-like growth factor (IGF) system is essential for normal growth and development, and its perturbation is implicated in a number of diseases. IGF activity is finely regulated by a family of six high-affinity IGF binding proteins (IGFBPs). 1GFBPs usually inhibit IGF actions but may enhance them under certain conditions. Additionally, IGFBPs bind non-IGF ligands in the extracellular space, cell membrane, cytoplasm and nucleus, thereby modulating cell proliferation, survival and migration in an IGF-independent manner. IGFBP activity is regulated by transcriptional mechanisms as well as by post translational modifications and proteolysis. Understanding the balance between the various actions of IGFBPs in vivo may lead to novel insights into disease processes and possible IGFBP-based therapeutics. PMID- 26841641 TI - The Effects of Electromagnetic Field on the Endocrine System in Children and Adolescents. AB - Children are exposed to various kind of non-ionizan radiation in their daily life involuntarily. The potential sensitivity of developing organism to the effects of radiofrequency (RF) signals, the higher estimated specific absorption rate (SAR) values of children and greater lifetime cumulative risk raised the scientific interest for children's vulnerability to electromagnetic fields (EMFs). In modern societies, children are being exposed to EMFs in very early ages. There are many researches in scientific literature investigating the alterations of biological parameters in living organisms after EMFs. Although the international guidelines did not report definite, convincing data about the causality, there are unignorable amount of studies indicating the increased risk of cancer, hematologic effects and cognitive impairment. Although they are less in amount; growing number of studies reveal the impacts on metabolism and endocrine function. Reproductive system and growth look like the most challenging fields. However there are also some concerns on detrimental effects of EMFs on thyroid functions, adrenal hormones, glucose homeostasis and melatonin levels. It is not easy to conduct a study investigating the effects of EMFs on a fetus or child due to ethical issues. Hence, the studies are usually performed on virtual models or animals. Although the results are conflicting and cannot be totally matched with humans; there is growing evidence to distress us about the threats of EMF on children. PMID- 26841642 TI - Nutrimetabolomics and Adipocitokines in the "Great Obstetrical Syndromes". AB - In neonatal medicine, nutritional research is focusing more and more on thrifty phenotype effects, in order to understand and prevent the development of long term diseases. lschemic placental disease which brings together Gestational diabete, Preeclamptic Toxemia, and Intrauterine Growth Restriction, the "Great Obstetrical Syndromes" (GOS), originates from sugar.and lipid metabolism. Adipokines and metabolomics can be valuable tools for the diagnosis of obstetrical syndromes and addressing nutrition. Inappropriate nutrition, even in the first periods of life, can accelerate the development of chronic metabolic diseases, especially in the pediatric age. The purpose of this review is firstly to critically examine the information provided by the studies of metabolomics on GOS's and better understand their origin. Secondly, it reflects on the IUGR metabolism and on applications of metabolomics in nutrition and its "nutrimetabolomic" effects and then to discuss the principles that guide nutrition of IUGR children in the light of these. PMID- 26841638 TI - Insulin-Like Growth Factor-I is a Marker for the Nutritional State. AB - Measurement of the serum concentration of insulin-like growth factor-I (IGF-l) is generally used as a screening investigation for disorders of the growth hormone (GH)/IGF-I axis in children and adolescents with short stature. IGF-I concentration is sensitive to short-term and chronic alterations in the nutritional state, and the interpretation of IGF-I measurements requires knowledge of the child's nutritional status. In this review, we summarize the effects of nutrition on the GH/IGF-I axis, and review the clinical implications of these interactions throughout childhood, both in under-nutrition and over nutrition. PMID- 26841643 TI - [Altered Z-disks of myofibrils in the cardiomyocytes from patients with Ebstein's anomaly]. AB - The aim of the study was to examine the peculiarities of the changes in Z-bands of myofibrils in the cardiomyocytes from patients with Ebstein's anomaly. MATERIAL AND METHODS: Electron microscopy assay of intraoperative biopsies of the right heart chambers in 41 patients aged from 9 months to 57 years was performed. RESULTS: Some patients exhibited Z-disk alterations of two types in individual cardiomyocytes, namely: local symmetrical bead-like expansions of Z-disks or longitudinal deposits of Z-material of different lengths along the myofibrils. Z disk alterations were more common in atrial cardiomyocytes than in the ventricle. The presence of Z-disk alterations in the cardiomyocytes correlated with a number of clinical parameters. In particular, the occurrence of longitudinal deposits of Z-material in atrial cardiomyocytes directly correlated with the manifestation of the Wolff-Parkinson-White syndrome in the patients. CONCLUSIONS: Above characteristic ultrastructural changes in Z-bands of myofibrils in the cardiomyocytes from patients with Ebstein's anomaly have a certain similarity to Z-band diseases in skeletal muscle at sarcomeric protein gene mutations described in the literature, which suggests the mutations in the genes of proteins included in Z-bands of myofibrils in the cardiomyocytes from patients with Ebstein's anomaly. PMID- 26841644 TI - [Adhesion molecules and mononuclear cell subpopulations in the coronary and pulmonary arteries of patients with coronary heart disease]. AB - Atherosclerosis is a multifactor disease, in which dysfunction of the endothelium leads to the emergence of its adhesion molecules. OBJECTIVE: to investigate the expression of the endothelial adhesion molecules PECAM (CD31), ICAM, and VCAM, as well as adherent endothelial T cells and monocytes. The material examined was en face pulmonary and coronary artery samples taken during autopsies (10 men), and en face specimens obtained from the coronary artery fragments taken from coronary heart disease patients during endarterectomy (37 men). This investigation used antibodies to the adhesion molecules ICAM-1, VCAM-1, and PECAM and those to CD3, CD4, CD8 T-cells and CD68 monocytes. RESULTS: The endothelial cells in the atherosclerotically intact coronary arteries had an elongated shape and were aligned along the blood flow. Those located above atheromas and fibroatheromas changed their shape from elongated to polygonal. Above the fatty streaks and atheromas, the reaction with antibodies to CD31 antigens became weaker at the edge of endothelial cells and disappeared in places. While the atherosclerotic process progressed, the reaction with the CD31 antigen at the edge of endothelial cells was similar in intensity to that on the surface of the endothelium. Adhesion of T cells and monocytes to the endothelium of coronary arteries increased as the atherosclerotic vascular process progressed. T cells and monocytes more often adhered to the endothelium at the sites where the endothelial cells contacted each other. CONCLUSION: Heterogeneity was found in the endothelial cells: their shape, the expression of adhesion molecules, and the adhesion of lymphocytes and monocytes to them changed during the progression of the atherosclerotic process. PMID- 26841645 TI - [Morphological characteristics of inflammation in HIV-associated pulmonary tuberculosis with regard to the expression of myeloperoxidase]. AB - OBJECTIVE: to characterize the morphological features of inflammation and the degree of myeloperoxidase expression in the lung of patients who died from HIV associated tuberculosis (TB). MATERIAL AND METHODS: Autopsy lung tissue specimens from 229 patients with HIV-associated TB were examined. A comparison group consisted of dead TB mono-infected patients (n = 30). Dead HIV/TB co-infected patients were divided into subgroups: 1) 50 patients with Stage 4A-4B and a CD4(+)-lymphocyte count of more than 200 cells/ul; 2) 54 with Stage 4B-4C and a CD4(+)-lymphocyte count of 100 to 200 cells/ul; 3) 125 with Stage 4C-5 and a CD4(+)-lymphocyte count of less than 100 cells/ul. Histological and immunohistochemical examinations of lung slices were performed using antibodies to myeloperoxidase (MPO). RESULTS: The predominant types of an inflammatory response were revealed according to the level of CD4+ lymphocytes. The lungs in Subgroup 1 showed a predominant typical granulomatous response (82%). Subgroup 2 exhibited an exudative-productive inflammatory response (57.4%) while Subgroup 3 displayed an alterative necrotic type (92.8%). Subgroup 3 showed the most marked reduction in lymphocyte numbers in the areas of inflammation, which was accompanied by a significant increase in the relative density and other morphometric parameters of MPO-positive macrophages and granulocytes in the inflammatory infiltration zones and alveolar walls. CONCLUSION: The identified changes in the lungs suggest that there is a decline in the magnitude of a delayed type hypersensitivity reaction, a progression of alterative necrotic processes as CD4(+) lymphocytes decrease in the systemic blood flow, and an increase in the proportion of functionally immature macrophages in the areas of inflammation, which reflects a substantially impaired local immune response to the persistence of M. tuberculosis in HIV infection. PMID- 26841646 TI - [Immunohistochemical changes in the lungs from fetuses and newborn infants at 20- 40 weeks' gestation with false left-sided congenital diaphragmatic hernia]. AB - OBJECTIVE: to study changes in the expression of growth factors in the lungs from fetuses and newborn infants at 20-40 weeks' gestation with false left-sided congenital diaphragmatic hernia (CDH). MATERIAL AND METHODS: Lung fragments obtained at autopsies were examined using immunohistochemically stained paraffin sections. The expression indices of insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and transforming grow factor-beta (TGF-beta) in the fetal lung sections were compared with the results of survey and elective staining techniques, the morphometric data of digitized lung sections, and the indicators obtained in the comparison group. RESULTS: Morphofunctional changes in the connective tissue, pulmonary vessels, and bronchial and alveolar epithelium at 20-24, 25-27, and 28-40 weeks' gestation were characterized, partly explaining the development of bilateral pulmonary hypoplasia in CDH. There was evidence for the involvement of PDGF, IGF 1, and EGF in primary pulmonary hypoplasia. PDGF deficiency plays a certain role in secondary pulmonary hypoplasia. CONCLUSION: The findings can be used in researches and in the practical work of pathologists and forensic medical experts. PMID- 26841647 TI - [Morphology of collagen matrices for tissue engineering (biocompatibility, biodegradation, tissue response)]. AB - OBJECTIVE: to perform a comparative morphological study of biocompatibility, biodegradation, and tissue response to implantation of collagen matrices (scaffolds) for tissue engineering in urology and other areas of medicine. MATERIAL AND METHODS: Nine matrix types, such as porous materials reconstructed from collagen solution; a collagen sponge-vicryl mesh composite; decellularized and freeze-dried bovine, equine, and fish dermis; small intestinal submucosa, decellularized bovine dura mater; and decellularized human femoral artery, were implanted subcutaneously in 225 rats. The tissues at the implantation site were investigated for a period of 5 to 90 days. Classical histology and nonlinear optical microscopy (NLOM) were applied. RESULTS: The investigations showed no rejection of all the collagen materials. The period of matrix bioresorption varied from 10 days for collagen sponges to 2 months for decellularized and freeze-dried vessels and vicryl meshes. Collagen was prone to macrophage resorption and enzymatic lysis, being replaced by granulation tissue and then fibrous tissue, followed by its involution. NLOM allowed the investigators to study the number, density, interposition, and spatial organization of collagen structures in the matrices and adjacent tissues, and their change over time during implantation. CONCLUSION: The performed investigation could recommend three matrices: hybrid collagen/vicryl composite; decellularized bovine dermis; and decellularized porcine small intestinal submucosa, which are most adequate for tissue engineering in urology. These and other collagen matrices may be used in different areas of regenerative medicine. PMID- 26841648 TI - [Investigation of the antioxidant activity and cardioprotective effect of reamberin and cytoflavin in newborn rats exposed to chronic hemic hypoxia]. AB - The authors analyzed the antioxidant activity of reamberin and cytoflavin and evaluated their cardioprotective effect, by investigating lipid peroxidation and oxidative modification of plasma proteins, as well as the ultrastructure of newborn rat cardiomyocytes under chronic hemic hypoxia induced by sodium nitrite. Reamberin and cytoflavin can reduce the manifestations of mitochondrial dysfunction and the degree of cardiomyocyte damage in the neonatal rats due to the antioxidant and membrane-protective properties of the drugs. Succinic acid in combination with the metabolic components of the drugs significantly inhibits lipid peroxidation, by improving the structure of membranes and the mitochondrial function of cardiomyocytes. PMID- 26841649 TI - [Histiocytoid cardiomyopathy concurrent with noncompact myocardium, myocarditis, and pericarditis]. AB - The paper presents a practical case of histiocytoid cardiomyopathy concurrent with noncompact myocardium, atrial septal defects, myocarditis, and pericarditis in an 8-month-old girl, by describing their clinical presentations and a morphological examination. PMID- 26841650 TI - [Renal urothelial carcinoma mainly composed of signet-ring cells]. AB - Autopsy study of an 80-year-old man has identified his renal tumor metastasizing to the heart, lung, and liver as urothelial car- cinoma; at the same time some cells in the main tumor and all cells in the metastases had a signet-ring phenotype, but neither mucicarcimine nor alcian blue stained the cell cytoplasm. The paper provides the histological and immunohistochemical pattern of the tumor and emphasizes its exclusive rarity. Attention is drawn to the possibility of signet-ring cell transformation in the cells of different tumors, including nonepithelial ones. PMID- 26841651 TI - [The immunosuppressive microenvironment of malignant gliomas]. AB - The dogma of the central nervous system (CNS) as an immune-privileged site has been substantially revised in recent years. CNS is an immunocompetent organ and actively interacts with the immune system. Microglia plays a leading role in a CNS immune response. However, in malignant gliomas, there is M2-polarization of microglia acquiring immunosuppressive and tumor-supportive properties. It occurs under the influence of tumor cytokines, such as transforming growth factor-beta, interleukin-10, and prostaglandin E2. M2-polarized microglia exhibits reduced phagocytic activity, changes in the expression of many cellular determinants, or inverse of their functions, STAT3 activation, and production of immunosuppressive cytokines that suppress the function of cytotoxic CD8+ T cells or CD4+ T-helper cells type I. Myeloid-derived suppressor cells and regulatory T-lymphocytes, which have been recruited from peripheral blood into tumor tissue, also have immunosuppressive properties. The development of new treatment options for malignant gliomas must consider the role of the microenvironment in maintaining tumor vitality and progression. PMID- 26841652 TI - [Nikolai Nikolaevich Anichkov (1885-1964)]. PMID- 26841653 TI - [Animal Models of Depression: Behavior as the Basis for Methodology, Assessment Criteria and Classifications]. AB - Analysis of the current state modeling of depression in animals is presented. Criteria and classification systems of the existing models are considered as well as approaches to the assessment of model validity. Though numerous approaches to modeling of depressive states based on disturbances of both motivational and emotional brain mechanisms have been elaborated, no satisfactory model of stable depression state has been developed yet. However, the diversity of existing models is quite positive since it allows performing targeted studies of selected neurobiological mechanisms and laws of depressive state development, as well as to investigate mechanisms of action and predict pharmacological profiles of potential antidepressants. PMID- 26841654 TI - [Cortical Functional Connectivity during Cued vs. Implicit Modality-Specific Anticipatory Attention: EEG-Source Alpha Coherence Analysis]. AB - The brain functional organization was studied in a group of healthy right-handed adults (N= 16, mean age = 23 +/- 5.7) during preparation for visual and auditory sensory tasks in two conditions: (1) participants waited for appearance of either a visual or an auditory stimulus after being cued about its sensory modality (the cued anticipatory attention) or (2) they developed implicit anticipation of stimulus in the course of repetitive exposure to the same sequence of visual and auditory stimuli pairs. In both cases, participants were asked to discriminate the temporal order of stimuli presentation within a pair of either visual or auditory modality. The functional connectivity was assessed via alpha coherence computed in the source space for preselected regions of interests. For both visual and auditory modalities, increase of strength of functional links among cortical areas involved in the fronto-parietal attention system is found during the cued attention when compared to nonspecific sustained attention. An increase is also observed in the connection strengths between sensory-specific and associative (parietal and prefrontal) areas. In visual modality, the buildup of implicit anticipation was accompanied by the strengthening of functional links between the ventral premotor cortex and caudal (parietal and occipital) areas of the right hemisphere. In the case of auditory task, the increase of connection strengths within fronto-temporal cortical areas was observed. These areas included the rostral supplementary motor areas, ventral premotor cortices and primary auditory cortices. PMID- 26841655 TI - [Changes of Alpha Cortical Potentials Spatial Synchronization on Value Go/NoGo Stimuli]. AB - At healthy people (n = 35) on model of the cognitive set on an angry face is shown: introduction of positive and negative coordinated stimuli Go/NoGo in the inter-stimuli interval can change considerably the top-down positive and negative influences of prefrontal cortex on the cortical areas participating in a visual perception and by that to influence plasticity of the set. The cortical topography of the top-down influences in response to NoGo is determined by local changes of power of fluctuations of potentials in alpha rhythm range. Changes of spatial synchronization of alpha potentials occurs only in their low-frequency range, depending on the level of plasticity of the set. At its rigid forms coherent communications between prefrontal and other cortical zones it is obviously more expressed in the left hemisphere. Apparently at rigid forms of cognitive activity left-side cortical activation with more essential involvement of speech, semantic functions, plays the compensating role. PMID- 26841656 TI - [The Modeling of Human Visual ERPs Sources in the Task of Line Orientation Identification]. AB - The high-resolution EEG was taken from 35 healthy subjects (16 males, 19 females) in the task of identification of cardinal (horizontal, vertical) and oblique (45 degrees , 135 degrees ) orientations. The integrated approach was developed and used for the ERPs analysis. It includes the modeling of the distributed intracranial dipole sources of the ERPs' components by the weighted Minimum Norm Estimates (wMNE) method, the combination of distributed intracranial dipole sources with the M RI data and the statistical analysis of the current density. It was shown that a multiple network of brain structures was active during the early stage of analysis of line orientation. It includes not only primary striate visual area, but also the parietal, temporal and prefrontal corticies. The new data was obtained about the participation of structures, responsible for navigation (parahippocampal gyrus and entorhinal area) in the line orientation detection. For the first time the gender-related differences in the organization ofthe line detection network were described. The obtained data provides a significant supplement to the knowledge of the mechanisms of the orientation sensitivity and assumes that orientation sensitivity plays an important role in the navigation. PMID- 26841657 TI - [Age Effect on Relationship Between Intelligence and EEG Characteristics]. AB - Age effect on EEG correlates of psychometrically estimated intelligence (IQ) in the younger (N = 132, age mean = 21.8 +/- 3.1) and elder groups (N = 84, age mean = 64.1 +/- 6.6) was studied. Regression analysis of individual alpha peak frequency's meanings, total power of biopotentials in eight frequency ranges indicated that a decrease of IQ correlates with age increase, or with decrease of individual alpha peak frequency with positive contribution of the alpha3 power and negative--of the beta1. High meaning of the alpha3 power and low meaning of the beta1 are the predictors of high intelligence in the younger group. High intelligence in the elder group is accompanied by a trend to increase of the individual alpha peak frequency and to decrease of the theta/beta1 power ration together with significant decrease of the alpha3/alpha2 power ratio. PMID- 26841658 TI - [Spatial Frequencies Priority in Attentional Capture]. AB - It was investigated whether the spatial frequencies are equal in their competition for attention. Two images of the same object were simultaneously presented (eccentricity 7 a.d.). They differed in spatial frequency. Attention capture was determined by the shift of gaze. Stimuli with spatial frequency 0.5, 1, 2, 4 and 8 cpd were used. The specific order of the spatial frequencies to attract attention was found. It was revealed that this sequence does not change when the category of objects changes. PMID- 26841659 TI - [The Effect of the Disease Duration on the Changes of the Visual Evoked Potentials and Contrast Sensitivity in Multiple Sclerosis]. AB - The most sensitive methods to detect pathological changes in the visual system are the method of recording visual evoked potentials and the psychophysical method of measuring contrast sensitivity. Described in the literature features of functional disorders of the visual system in patients with multiple sclerosis are controversial. The results of the study allowed us to make an assumption about the depen-dence of the nature and severity of changes of the evoked potentials and contrast sensitivity and the duration of disease in patients with multiple sclerosis. In some patients with disease duration from 3 to 10 years there are irregularities in the magno-channels (reduced amplitude component P1), in others- parvo-channels (amplitude reduction N 1) without increasing the latency, in patients with a disease duration of 10 to 14 years--both channels dysfunction (decreased amplitude components P1 and N1) with an increase of latency. The data indicate heterogeneity of pathophysiological changes upon increase of the degree of demyelination and damage of optic nerve fibers in multiple sclerosis. PMID- 26841660 TI - [The Manifestation of the Anxiety during Fear Conditioning in Wistar Rats]. AB - In order to identify the correlation between anxiety and conditioned fear, the behavior of the same male Wistar rats was compared in three anxiety tests (open field, light-dark box and elevated plus-maze) and in Pavlovian auditory fear conditioning paradigm using correlation, factor and variance analyses. The correlation between anxiety/bravery and locomotion indexes in different tests was not revealed. Positive correlations between grooming, urinations and defecations, rearing in three tests were revealed. These data suggest that animals reacted to various tests differently, resulting, apparently in the emergence of different anxiety levels, specific for each test. Vegetative reactions, inclination to exploration and substituting behavior were more stable characteristics of rats. Anxiety behavior in elevated plus-maze correlated to freezing response to context after fear conditioning, while high-anxiety rats had higher level of freezing to context than low-anxiety rats. The higher freezing response to sound after fear conditioning was found in rats with middle locomotor activity in open field. Conditioned fear to the context and to the sound was associated with different forms of rat anxiety during different tests. PMID- 26841661 TI - [Influence of GABA(C)-Receptor Antagonist on Formation of Evoked Potentials in Columns of the Rat Somatosensory Cortex]. AB - Microelectrode studies of evoked potentials (EP) in neuronal column of rats barrel cortex show activating action of selective GABA(C)-receptor antagonist 1,2,5,6-tetrahydropyridin-4-yl-methylphosphinic acid (TPMPA) mainly on secondary components of EP of supragranular afferent layers of column compared to the efferent infragranular layers. These data suggest localization of GABA(C) receptors on pre- synaptic terminals of thalamo-cortical glutamatergic afferents and ascending apical dendrites of pyramidal cells. A blockade of GABA(C) receptors with the selective antagonist TPM PA leads to dose-dependent afferent depolarization with development of presynaptic inhibition and suppression of primary components of EP GABA(C)-receptors blocker produces different effects on secondary components of EP in supragranular layers of the cortex caused by the development of neuronal after hyperpolarization followed by high-amplitude primary response and afterdepolarization followed by low-amplitude primary responses with subsequent activation of different voltage-gated channels and formation of different level of cortical direct current potential gradients. PMID- 26841662 TI - [Effect of Agonists and Antagonists of alpha2 Adrenergic Receptors on Choice of Reinforcement Value in Rats with Different Levels of Impulsivity]. AB - The influence of drugs, agonist (clonidine) and antagonist (yohimbine) of alpha2 adrenergic receptors 5-HT2 on the behavior of rats tested by the method of choice to the value of reinforcement was investigated. Based on the selection of a rat the pedal for immediate poor and delayed valuable reinforcement rats were divided into 3 groups. Rats, in most cases, choosing valuable delayed reinforcements were classified as low-impulsive, those who mainly chosen poor immediate reinforcement to the high-impulsive group. Rats who were not able to determine, was ambivalent group. Administration (i.p.) of the alpha2-adrenergic receptors agonist clonidine resulted in a reduction of the select valuable delayed reinforcement by low impulsive animals and increasing the number of missing responses of pressing the pedal in high-impulsive animals. Clonidine also reduced the latency of nose poking in all groups of animals. The antagonist of these receptors yohimbine did not cause changes in the choice of the reinforcement in all groups of animals. At the same time yohimbine caused a significant reduction in the number of missing responses. The results suggest that the effect of drugs used in this work on alpha2-adrenergic receptors depends on the individual feature of rats, in particular from high and low degree of impulsivity. PMID- 26841663 TI - [Sex Differences in Behavioral Reactions and the Character of Audiogenic Seizures in Krushinsky-Molodkina Rat Strain]. AB - In the "open field" test it was found that locomotor activity in Krushinsky Molodkina rat strain (KM) is higher than in nonlinear animals. At the same time, both groups of animals had the same sex differences: a locomotor activity of females was higher than males. Sex differences in exploratory activities are not inherent for KM rats, while the female outbred animals are significantly higher than males in their level of such activities. The greatest differences in behavior between KM rats and outbred animals were found in anxiety level, which is much higher in the first case. Furthermore just KM rats are characterized by clear sex differences--the males demonstrate more anxious and fearful respond to unfamiliar surroundings than females. Male and female KM rats differ not only in behavior but also in the character of epileptiform seizures induced by loud sound: wild running, tonic-clonic and clonic convulsions occur faster in females and the resumption of breathing-in males. The interconnection between parameters of seizure and behavior was found for KM rats. This phenomenon is most clearly manifested in males and combine large group of indicators. PMID- 26841664 TI - [THE EFFECT OF SATINS: ACTIVATION OF LIPOLYSIS AND ABSORPTION BY INSULIN-DEPENDED CELLS LIPOPROTEINS OF VERY LOW DENSITY, INCREASING OF BIO-AVAILABILITY OF POLYENOIC FATTY ACIDS AND DECREASING OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY]. AB - The Russian cardiologic R&D production complex of Minzdrav of Russia, 121552 Moscow, Russia The statins are synthetic xenobiotics alien to animal cells. They are unlikely capable to manifest pleiotropic effect. It is feasible to evaluate effect of statins by stages: a) initially a specific inhibition of synthesis of cholesterol alcohol; b) further indirect activation of hydrolysis of triglycerides in lipoproteins of very low density; c) nonspecific activation of cells' receptor absorption of palmitic and oleic lipoproteins of very low density and then d) linoleic and linolenic lipoproteins of low density with all polyenoic fatty acids. On balance, statins activate absorption ofpolyenoic fatty acids by cells. Just they manifest physiological, specific pleiotropic effect. The statins inhibit synthesis of pool of cholesterol alcohol-lipoproteins of very low density condensed between phosphatidylcholines in polar mono-layer phosphatidylcholines+cholesterol alcohol on surface oftriglycerides. The low permeability of mono-layer separates substrate-triglycerides in lipoproteins of very low density and post-heparin lipoprotein lipase in hydrophilic blood plasma. The higher is ratio cholesterol alcohol/phosphatidylcholines in mono-layer of lipoproteins of very low density the slower is lipolysis, formation of ligand lipoproteins of very low density and their absorption by cells under apoB-100 endocytosis. The statins normalize hyperlipemia by force of a) activation of absorption oflipoproteins of very low density by insulin-depended cells and b) activation of absorption of lipoproteins of low density by all cells, increasing of bio-availability of polyenoic fatty acids, activation of apoB-100-endocytosis. The limitation in food of content of palmitic saturated fatty acid and increasing of content of omega-3 polyenoic fatty acids improve "bio-availability" of polyenoic fatty acids and their absorption by cells and also decreases cholesterol alcohol/phosphatidylcholines and biological pleiotropic effect of essential polyenoic fatty acids. According our opinion, atherosclerosis is intracellular deficiency of polyenoic fatty acids. The value of cholesterol alcohol-lipoproteins of low density is equimolar to content of lipoproteins of low density in blood which under low bio-availability can't to absorb cells byforce of apoB-100-endocytosis. PMID- 26841665 TI - [THE CLINICAL LABORATORY MARKERS OF ATHEROSCLEROSIS IN PATIENTS WITH ATHEROTHROMBOTIC STROKE]. AB - The laboratory biomarkers can effect on choice of tactics of treatment in patients with atherosclerotic stenosis ofcarotids and high risk of stroke. However, nowadays there is no established laboratory criteria of significant atherosclerotic affection of internal carotid. The purpose of study was to investigate informativeness of biomarkers of atherosclerosis in clinical molecuIar panel of expertise system of determining risk of stroke in patients with significant stenosis of carotid. The study included patients with 50-90% atherosclerotic stenosis of internal carotid in acute period of atherothrombotic stroke or transitory ischemic attack (group 1), patients with stable 50-90% atherosclerotic stenosis of inner carotid having no vascular events during 30 days before engaging into study (group II) and group of healthy volunteers without atherosclerosis of inner carotid. The examination of patients included anamnesis collection, evaluation of neurological status, analysis of serum level of biomarkers of atherosclerosis (lipoprotein-associatedphospholipase A2 (LP-PL A2), serum protein A associated with pregnancy (PA PP-A), lipoprotein (a) (LP(a)), asymmetric dimethylarginine (ADMA), C-reactive protein detected by highly sensitive technique (hsCRP) and lipid spectrum of blood) using enzyme linked immunosorbent assay, duplex ultrasound scanning of brachiocephalic arteries. The stroke risk factors of other etiology were chosen as exclusion criteria except atherothrombotic one. The Mann-Whitney and Kruskal-Wallis tests were applied to establish group differences. The Data Mining techniques were applied to establish patterns of analyzing sample. Out of 356 examined patients, 30 patients of group 1, 51 patients of group II and 16 healthy volunteers were included in the study. All patients were comparable by gender and age (50-80 years). The serum level of hsCRP and ADMA in the group of patients of acutest period of ischemic stroke was significantly higher than in groups of patients with stable stenosis and healthy volunteers (p < 0.05). The comparison between three groups established no statistically significant differences in serum concentration of PAPP-A, LP-PL A2 and LP(a). The ADMA, hsCRP and PAPP-A can be recommended for including into clinical molecular panel for personalized diagnostic of causes of stroke along with clinical anamnestic data. The serum level of ADMA and hsCRP significantly increases in acute period of atherothrombotic stroke. The analysis of levels of ADMA, hsCR and PPAPP-A interpreted with regard to clinical anamnestic data can be proposed for enhancing quality of diagnostic of causes of stroke. PMID- 26841666 TI - [THE POSSIBILITIES OF APPLICATION OF TECHNOLOGY PROTEIN MICROARRAY (MICROCHIPS) FOR ANALYSIS OF PROTEIN COMPOSITION OF BLOOD SERUM]. AB - The microchip technology represents convenient and relatively economic tool of analyzing specific biomarkers with the purpose to diagnose diseases, to evaluate effectiveness of therapy and to investigate signaling pathways. To analyze protein composition of blood serum certain types of finished microchips which were not applied previously on the territory of Russia. The detection from 2% to 5% out of matrix of chips depending on their variety was managed without preliminary depletion of serum (removal of proteins of major fractions). Hence, partial protein composition of blood serum can be analyzed with microchips even without preliminary removal of proteins of major fractions. PMID- 26841667 TI - [THE ANALYSTS OF PROCALCITONIN IN LACRIMAL FLUID AND BLOOD SERUM UNDER UVEITIS]. AB - The analysis was applied to concentration of procalcitonin in lacrimal fluid and blood serum in 15 healthy persons (control group), 16 patients with uveitis (main group) and 14 patients with non-inflammatory pathology of organ of vision (comparison group). The concentration of procalcitonin was detected by immunoenzyme method using commercial test-system "Procalcitonin-IFA-BEST" ("Vector-Best", Russia). The content of procalcitonin in blood serum was low (75% quartile--0.031 ng/ml) and had no significant difference between groups (H criterion of Kruskal-Wallis test, p = 0.0872). The level of procalcitonin in lacrimal fluid 8-11 times exceeded its concentration in blood serum of all groups (Wilcoxon criterion, p < 0.005). The least content of procalcitonin is detected in lacrimal fluid of patients of comparison group (0.072 +/- 0.064 ng/ml). In main and control groups its level was reliably higher (H-criterion of Kruskal Wallis test, p = 0.0002) and amounted to 0.257 +/- 0.146 and 0.198 +/- 0.151 ng/ml correspondingly. The correlation analysis established no dependencies between concentration of procalcitonin in tear and blood serum (Spearman correlation coefficient had no exceeding |0.1| in all groups). The development of uveitis is not accompanied by alteration of concentration of procalcitonin in both blood serum and lacrimal fluid. The absence of correlation and higher concentration of procalcitonin in tear as compared with blood serum testify availability of additional source of this protein in lacrimal fluid. PMID- 26841668 TI - [THE ANALYSIS OF ASSOCIATION OF MATRIX METALLOPROTEINASE-9 AND TISSUE INHIBITOR OF METALLOPROTEINASE-1 WITH LEVEL OF ZINC IN DIFFERENT BIO SUBSTRATES IN PATIENTS WITH CAROTID STENOSIS]. AB - The levels of matrix metalloproteinase-9 and its tissue inhibitor-1 and also zinc in serum, hair and biopsy material of atherosclerosis plaques of carotid in patients with carotid stenosis. The analysis of association between these two indicators was implemented. The highest indicators of matrix metalloproteinase-9, tissue inhibitor-I and index matrix metalloproteinase-9/tissue inhibitor-1 in patients with carotid stenosis more than 50% were established. The negative correlation between zinc concentration in serum and thickness of complex intima media of common carotid artery was established. The weak inverse correlation of matrix metalloproteinase-9 with zinc level in atherosclerosis plaques. PMID- 26841669 TI - [THE COMPARISON OF TECHNIQUES OF ELECTROPHORESIS, IMMUNE TURBIDYNAMIC MEASUREMENT AND PHENOTYPING OF ALPHA-1-ANTITRYPSIN FOR DIAGNOSTIC OF ALPHA-1-ANTITRYPSIN INSUFFICIENCY]. AB - The qualitative and quantitative deficiency of alpha-1-antitrypsin (A1AT) is an inherited factor of susceptibility to a number of conditions including chronic obstructive disease of lungs and primary emphysema and liver affection. The study was carried out to evaluate analysis of alpha-1-fraction (A1F) using zonal electrophoresis technique for detecting patients with alpha-1-antitrypsin insufficiency (A1ATI). The patients with decreased (group I) and normal (group II) A1F on proteinogram. The electrophoresis was applied using the system of capillary electrophoresis Capillaris-2 Flex Piercing (Sebia, France) and also system for electrophoresis in agarose gel SAS-1/SAS-2 (Helena Biosciences, Great Britain). The commercial kit Sentinel diagnostics (Italy) and biochemical analyzer A15 (Biosystems, Spain) were used for quantitative detecting of A1AT The study results demonstrated that decreasing of A1F on proteinogram correlated with lessening of concentration of A1ATI in blood serum and with presence of its pathological phenotype. The average values of concentration of A1AT in group I and group II made up to 1148 and 1738 mg/I correspondingly. The total rate of pathological phenotypes made up to 76% (19/25) in group I that reliably differed from indicators in group II--7.1% (2/28). Thereby, electrophoresis of proteins of blood serum can be sufficiently informative for primary selection of patients requiring examination for presence of A1ATI. PMID- 26841670 TI - [THE MODE OF CLARIFYING DIAGNOSTIC OF PROGRESSING FORMS OF OVARIAN CARCINOMA]. AB - The ovarian carcinoma is the most frequent cause of death because of malignant neoplasins in women. At that, there is no pathognomonic symptoms permitting diagnosing stage of process with sufficient degree of confidence. This is a determinative not only for choosing treatment regimen but also for correlation of expected results of treatments with economic factors with purpose to evaluate cost effectiveness under monitoring of these patients. The study was carried out to develop mode of clarifying diagnostic of progressing forms of ovarian carcinoma on the basis of evaluation of oxidative modification of proteins in blood plasma. In 100 female patients with primary ovarian carcinoma (stage III and IV according FIGO,) in blood plasma 21 indicators were determined in blood plasma using standardized techniques: absolute number of leukocytes, absolute and relative number of neutrophils, products of oxidative modification of proteins of basic and ketonic character (under wavelength of 356, 370, 430, 530 nm), Her 2/neu CA-125, matrix metalloproteinase 2 and 9 in blood serum and neutrophils, interleukin-6, interleukin-10, interleukin-1beta, interferon-gamma, tumor necrosis factor-alpha, malonic dialdehyde, catalase, glutaihione transferase, glutathione reductase. The least squares method was applied to every parameter to appmximnate relative rates by density of Rayleigh distribution. For every indicator likelihood ratio functions of likelihood ratio were constructed and intervals at every stage were determined. The reliability of approximation was proved under testing with Pirson criterion hypothesis of compliance of practical values of parameters to theoretical law of density of distribution. The results permit to assert that level of oxidative modification of proteins cab be used as a reliable indicator for differentiated diagnostic of stage III and IV of ovarian carcinoma. PMID- 26841671 TI - [THE SELECTION OF ANTIGENS FOR DETECTING OF IMMUNOGLOBULIN G TO CYTOMEGALOVIRUS ON THE BASIS OF FOSFAN TECHNOLOGY]. AB - The results of selection of composition of antigens to cytomegalovirus in the structure of multiplex test on the basis of FOSFANTM technique are presented. In the process of detection of immunoglobulin G (IgG) to this virus the best indicators of sensitivity were registered with mosaic antigen containing immunodominant sequences of proteins pp150, gB, pp28 and pp52; reliably lower indicators of sensitivity was registered with phosphoprotein pp150; the lowest indicators of sensitivity were registered with proteins gB and pp65. The specificity made up from 93.5% to 96.8% independently of type of antigen. The mosaic antigen ensured the best ratio between sensitivity and specificity of immunoassay and is considered as the main component of immunochip for detecting IgG to cytomegalovirus. PMID- 26841672 TI - [THE CHARACTERISTICS OF SYSTEMIC AND LOCAL IMMUNE REACTIONS UNDER HABITUAL NON CARRYING OF PREGNANCY]. AB - The study was carried out to evaluate clinical informativeness ofstudies of immunological parameters of structural and functional elements of endometrium in complex with profile of embritropic autoimmune antibodies under non-carrying of pregnancy The sampling consisted of 19 women of reproductive age with episodes of non-carrying in first semester. They were examined for inherited thrombophilia and profiles of immune reactivity of natural regulatory auto-antibodies (ELI-P Complex). The biopsy material of endometrium was subjected to histological and immune histochemical (CD16, CD56, CD68, CB138, estrogen and progesterone receptors) analyses. In women with non-carrying of pregnancy polyclonal immunosuppression, increased level of embriotoxic auto antibodies to Fc- fragment of immunoglobulin, insulin and thyroglobulin are detected. The immune histochemical analysis established expressed decreasing of amount of progesterone receptors of stromal elements of endometrium after spontaneous abortion. The activation of killer activity of decidual lymphocytes under habitual non-carrying of pregnancy was detected too. The positive dependency was established between: expression of progesterone receptors in glandular cells of endometrium and level of anti-spermatic antibodies in blood serum; expression of progesterone receptors in stroma and level of antibodies to human chorial gonadotropin; expression of receptors of estrogens in stroma and level of antibodies to Fc-fragment of immmunoglobulines. The study data permits affirming that evaluation of level of regulatory auto-antibodies is informative at examination of woman after episode of non-carrying of pregnancy. The production of antibodies has direct relationship with pathological processes in endometrium and it can be one of criteria of completeness of pre-conceptional preparation. PMID- 26841673 TI - [THE IMMUNOMODULATORY ACTIVITY OF PLASMA OF PATIENTS INFECTED WITH HUMAN HIV VIRUS]. AB - The study was carried out to investigate impact of plasma of patients infected with human HIV virus receiving and not receiving highly active antiviral therapy on: expression of phenotypic markers of lymphocytes (CD3+, CD3+/CD4+, CD3+/CD8+, CD19+, CD3-/CD (16+56)+, CD3+/CD(16+56)+, CD3+/HLA-DR+, CD4+/CD62L+, CD8+/CD38+) in mononuclear cells of blood of donors and secretion of pro-inflammatory (interleukin-1beta, interferon-gamma, tumor necrosis factor-alpha, interleukin-4 and interleukin-10) cytokines. After 24 hours of activation of mononuclear cells with plasmas it was demonstrated that as compared with control groups, in of plasmas of patients with highly active antiviral therapy increasing of number of CD4+ T-cells and decreasing of CD8+ T-cells is observed. The plasmas of patients with highly active antiviral therapy activate in most instances CD4+ T-cells whereas plasmas of patients without treatment--CD8+ T-cells. The results of detection of cytokines in blood indicate that in patients without treatment inflammatory potential is increased as compared with group of highly active antiviral therapy. The data concerning accumulation of interleukin-1beta under cultivation of mononuclear cells with plasmas indicates at its role in preservation of vitality of natural killers. The analysis of immunomodulatory activity of plasma of patients infected with human HIV virus can be recommended as an additional technique of evaluation of functioning of immune system. PMID- 26841674 TI - [THE SPECIES CHARACTERISTIC OF BIFIDOBACTERIA IN INTESTINAL BIOTOPE OF CHILDREN WITH FUNCTIONAL DYSPEPSIA]. AB - The study was carried out to investigate species specter and combinational variety of bifidobacteria in children with functional dyspepsia. The examined sampling included 73 children with functional dyspepsia aged from 4 to 6 years. The comparison group according common characteristic of microbiota of large intestine included 100 healthy children comparative by age. In 32 out of all examined children species specter of bifidobacteria in intestine was analyzed. The species diagnostic of bifidobacteria was implemented by using technique of polymerase chain reaction. In children with functional dyspepsia the analysis established dysbiosis alterations in intestinal biotope, characterizing by deficiency of bifidobacteria and selection of opportunistic microorganisms. The alteration of species structure of bifidobacteria in children with functional dyspepsia is demonstrated: decreasing of prevalence of populations of Bifidobacterium catenulatum and appearance of rare species of bifidobacteria B. dentium and B. angulatum. The differences are established concerning formation of species preference of bifidobacteria in conditions of conjoint vegetation in intestinal biotope of children with functional dyspepsia and in healthy children. The comprehensive analysis of micro-ecological status of intestine of children with functional dyspepsia using non-invasive techniques and including analysis of species profile, associative potential, communicative capacities of bifidobacteria complements complex of diagnostic criteria, permits to develop prognostic markers and to determine parameters of following therapy of functional dyspepsia. PMID- 26841675 TI - [THE ROLE OF SYSTEM QUORUM SENSING UNDER CHRONIC UROGENITAL CHLAMYDIA INFECTION]. AB - It is established that system quorum sensing (QS) assure social behavior of bacteria in regulation of genes of virulence and generalization of inflectional inflammatory process under chronic urogenital chlamydia infection. The techniques of gas chromatography and mass-spectrometry were applied to detect molecular markers of generalization of infectious process under urogenital chlamydiasis- activators of QS microbes (lactones, quinolones, furan ethers). The developed diagnostic gas chromatography and mass-spectrometry criteria of indexation of molecular markers under chronic urogenital chlamydia infection have high level of diagnostic sensitivity, specificity and prognostic value of positive and negative result. The application of techniques of gas chromatography and mass-spectrometry permits enhancing effectiveness of diagnostic of chronic inflectional inflammatory diseases of urogenital system of chlamydia etiology with identification of prognostic criteria of generalization of infectious process and subsequent prescription of timely and appropriate therapy PMID- 26841676 TI - [THE SPECIES COMPOSITION OF AGENTS OF COMMUNITY-ACQUIRED INFECTIONS OF URINARY TRACTS AND SENSITIVITY OF MAIN UROPATHOGENS TO ANTIBACTERIAL PREPARATIONS IN MOSCOW IN 2013]. AB - The article presents the results of analysis of spectrum of agents of community acquired infections of urinary tracts in Moscow The prevalence of resistance these infections to antibiotics applied in treatment of the mentioned pathology are considered. PMID- 26841677 TI - [THE MICROBIAL CONTAMINATION OF PERINEAL WOUNDS AS RISK FACTOR OF POST-OPERATIVE PURULENT COMPLICATIONS IN PROCTOLOGIC PATIENTS]. AB - The bacterial analysis of wound secretion of perineal wounds before their closure in coloproctologic patients established microbial contamination of 92% of cases. The post-operative wound abscesses, developed against this background, made up to 16.7% in control group and only 2% (p < 0.001) in main group where technique of double crossed prolonged flow suction drainage was applied In all patients with developed wound abscesses the monocultures of microorganisms or their associations were obtained by intraoperational way. PMID- 26841678 TI - External validation of the MetS score, a prediction tool for metabolic syndrome. PMID- 26841679 TI - Epicardial adipocyte hypertrophy: Association with M1-polarization and toll-like receptor pathways in coronary artery disease patients. AB - BACKGROUND AND AIMS: In coronary artery disease (CAD) epicardial adipose tissue (EAT) shows an elevated inflammatory infiltrate. Toll-like receptors (TLRs) are important mediators of adipose tissue inflammation and they are able to recognize endogenous products released by damaged cells. Because adipocyte death may be driven by hypertrophy, our aim was to investigate in CAD and non-CAD patients the association between EAT adipocyte size, macrophage infiltration/polarization and TLR-2 and TLR-4 expression. METHODS AND RESULTS: EAT biopsies were collected from CAD and non-CAD patients. The adipocyte size was determined by morphometric analysis. Microarray technology was used for gene expression analysis; macrophage phenotype and TLRs expression were analyzed by immunofluorescence and immunohistochemical techniques. Inflammatory mediator levels were determined by immunoassays. EAT adipocytes were larger in CAD than non-CAD patients and do not express perilipin A, a marker of lipid droplet integrity. In CAD, EAT is more infiltrated by CD68-positive cells which are polarized toward an M1 state (CD11c positive) and presents an increased pro-inflammatory profile. Both TLR-2 and TLR 4 expression is higher in EAT from CAD and observed on all the CD68-positive cells. CONCLUSIONS: Our findings suggested that EAT hypertrophy in CAD promotes adipocyte degeneration and drives local inflammation through increased infiltration of macrophages which are mainly polarized towards an M1 state and express both TLR-2 and TLR-4. PMID- 26841681 TI - The Role of Clozapine in Treatment-Resistant Schizophrenia. PMID- 26841680 TI - Neural innervation stimulates splenic TFF2 to arrest myeloid cell expansion and cancer. AB - CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) expand in the spleen during cancer and promote progression through suppression of cytotoxic T cells. An anti-inflammatory reflex arc involving the vagus nerve and memory T cells is necessary for resolution of acute inflammation. Failure of this neural circuit could promote procarcinogenic inflammation and altered tumour immunity. Here we show that splenic TFF2, a secreted anti-inflammatory peptide, is released by vagally modulated memory T cells to suppress the expansion of MDSCs through CXCR4. Splenic denervation interrupts the anti-inflammatory neural arc, resulting in the expansion of MDSCs and colorectal cancer. Deletion of Tff2 recapitulates splenic denervation to promote carcinogenesis. Colorectal carcinogenesis could be suppressed through transgenic overexpression of TFF2, adenoviral transfer of TFF2 or transplantation of TFF2-expressing bone marrow. TFF2 is important to the anti inflammatory reflex arc and plays an essential role in arresting MDSC proliferation. TFF2 offers a potential approach to prevent and to treat cancer. PMID- 26841682 TI - A polyarticular onset and diabetes could be the main predictors of cardiovascular events in psoriatic arthritis. AB - OBJECTIVES: We aimed to determine which disease features could be associated to the risk of cardiovascular (CV) events in a PsA cohort from a tertiary care institution. METHODS: We conducted an age- and sex-matched case-control study in which the cases were all PsA patients who developed cardiovascular (CV) events during the study period (2010-14). The control group was free of CV events during the same period. Univariate analysis was performed to examine unadjusted associations of potential risk factors. Significant variables in the univariate analysis were then introduced in a multivariate analysis with a backward stepwise approach. RESULTS: Of the 206 patients enrolled, 17 (8.3%) patients developed a total of 25 CV events (10 stroke, 9 acute coronary events and 6 ischaemic peripheral vascular events). In univariate analysis these patients showed more pustular psoriasis (OR 5.5, p=0.02), polyarticular onset (OR 3.2, p=0.03), polyarthritis during follow-up (OR 2.9, p=0.04), arthritis onset after 40 yr (OR 3.7, p=0.02), high lipid levels (OR 2.8, p=0.04), hypertension (OR 6.4, p=0.0008), diabetes (OR 12.1, p<0.0001) and lower educational level (OR 3.2, p=0.05). After controlling for age and other confounders, a polyarticular onset of PsA (OR 3.7, p=0.043) and diabetes (OR 8.1, p=0.001) remained as independently related to the risk of CV events. CONCLUSIONS: Traditional CV risk factors as well as factors related to the inflammatory nature of the disease were the main predictors of CV complications in this PsA population. PMID- 26841687 TI - Bone: The circadian clock controls bone remodelling. PMID- 26841683 TI - Cross Reactive Material 197 glycoconjugate vaccines contain privileged conjugation sites. AB - Production of glycoconjugate vaccines involves the chemical conjugation of glycans to an immunogenic carrier protein such as Cross-Reactive-Material-197 (CRM197). Instead of using glycans from natural sources recent vaccine development has been focusing on the use of synthetically defined minimal epitopes. While the glycan is structurally defined, the attachment sites on the protein are not. Fully characterized conjugates and batch-to-batch comparisons are the key to eventually create completely defined conjugates. A variety of glycoconjugates consisting of CRM197 and synthetic oligosaccharide epitopes was characterised using mass spectrometry techniques. The primary structure was assessed by combining intact protein MALDI-TOF-MS, LC-MALDI-TOF-MS middle-down and LC-ESI-MS bottom-up approaches. The middle-down approach on CNBr cleaved glycopeptides provided almost complete sequence coverage, facilitating rapid batch-to-batch comparisons, resolving glycan loading and identification of side products. Regions close to the N- and C-termini were most efficiently conjugated. PMID- 26841688 TI - Osteoarthritis: Galectin-1 damages cartilage via inflammation. PMID- 26841690 TI - Autoimmunity: TFH cells link gut microbiota and arthritis. PMID- 26841691 TI - Connective tissue diseases: Nucleosomes and systemic sclerosis. PMID- 26841693 TI - Guidelines for Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy (JCS 2012) - Digest Version . PMID- 26841692 TI - Growing Embossed Nanostructures of Polymer Brushes on Wet-Etched Silicon Templated via Block Copolymers. AB - Block copolymer nanolithography has attracted enormous interest in chip technologies, such as integrated silicon chips and biochips, due to its large scale and mass production of uniform patterns. We further modified this technology to grow embossed nanodots, nanorods, and nanofingerprints of polymer brushes on silicon from their corresponding wet-etched nanostructures covered with pendent SiHx (X = 1-3) species. Atomic force microscopy (AFM) was used to image the topomorphologies, and multiple transmission-reflection infrared spectroscopy (MTR-IR) was used to monitor the surface molecular films in each step for the sequential stepwise reactions. In addition, two layers of polymethacrylic acid (PMAA) brush nanodots were observed, which were attributed to the circumferential convergence growth and the diffusion-limited growth of the polymer brushes. The pH response of PMAA nanodots in the same region was investigated by AFM from pH 3.0 to 9.0. PMID- 26841694 TI - Effects of 4-phenylbutyrate therapy in a preterm infant with cholestasis and liver fibrosis. AB - The bile salt export pump is expressed at the canalicular membrane of hepatocytes and mediates biliary excretion of bile salts. 4-Phenylbutyrate (4 PB), a drug used to treat ornithine transcarbamylase deficiency, has been found to increase the hepatocanalicular expression of bile salt export pump. The beneficial effects of 4-phenylbutyrate therapy have been reported for patients with progressive familial intrahepatic cholestasis, an inherited autosomal recessive liver disease. This is the first study to show the therapeutic effect of 4 PB in a preterm infant with cholestasis and liver fibrosis. The preterm infant had severe cholestasis with jaundice and failure to thrive refractory to ursodeoxycholic acid. Histology indicated giant cell hepatitis, cholestasis, and severe fibrosis. Bile salt export pump immunostaining showed lower expression than in a control. Oral 4 PB was started at a daily dose of 200 mg/kg/day. After the start of 4 PB therapy, cholestasis improved. PMID- 26841695 TI - Identification of a novel missense mutation (563G>a) in the ABO gene associated with a Bel phenotype. PMID- 26841697 TI - Isolation and structure elucidation of unexpected in-process impurities during tetrazole ring formation of an investigational drug substance. AB - During the formation of a tetrazole ring on an investigational drug, two in process impurities were detected and analyzed by LC-MS, which suggested that both impurities were drug-related with the same mass-to-charge ratio. To understand and control their formation, both impurities were isolated from the mother liquor of the reaction using a multi-step isolation procedure to obtain a sufficient amount for high-resolution mass spectrometry (HRMS) and NMR structural analysis. HRMS suggested a protonated mass of 577.32 Da for both impurities; however, MS fragmentation patterns provided limited information on their structures. NMR analysis indicated the presence on an additional NH functional group in both isolates with similar spatial and bond correlations to one of the dimethylcarbamoyl moieties and the corresponding aromatic ring. A phenyldimethylcarbamoylamino moiety was supported by the NMR and HRMS data and could be explained based on the 'Schmidt-like' reaction mechanism, which was an unexpected reaction pathway. Because the reaction conditions were fixed because of safety concerns, the crystallization protocol was redesigned to reduce the levels of these impurities significantly. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26841696 TI - Cohesin-interacting protein WAPL-1 regulates meiotic chromosome structure and cohesion by antagonizing specific cohesin complexes. AB - Wapl induces cohesin dissociation from DNA throughout the mitotic cell cycle, modulating sister chromatid cohesion and higher-order chromatin structure. Cohesin complexes containing meiosis-specific kleisin subunits govern most aspects of meiotic chromosome function, but whether Wapl regulates these complexes remains unknown. We show that during C. elegans oogenesis WAPL-1 antagonizes binding of cohesin containing COH-3/4 kleisins, but not REC-8, demonstrating that sensitivity to WAPL-1 is dictated by kleisin identity. By restricting the amount of chromosome-associated COH-3/4 cohesin, WAPL-1 controls chromosome structure throughout meiotic prophase. In the absence of REC-8, WAPL-1 inhibits COH-3/4-mediated cohesion, which requires crossover-fated events formed during meiotic recombination. Thus, WAPL-1 promotes functional specialization of meiotic cohesin: WAPL-1-sensitive COH-3/4 complexes modulate higher-order chromosome structure, while WAPL-1-refractory REC-8 complexes provide stable cohesion. Surprisingly, a WAPL-1-independent mechanism removes cohesin before metaphase I. Our studies provide insight into how meiosis-specific cohesin complexes are regulated to ensure formation of euploid gametes. PMID- 26841698 TI - Somatic mutations of DICER1 and KMT2D are frequent in intraocular medulloepitheliomas. AB - Intraocular medulloepithelioma (IO-MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. Little is known about the cytogenetics, molecular biology, and pathogenesis of this tumor. In the present study we investigated the mutational landscape of 19 IO-MEPL using targeted next-generation sequencing. Routinely prepared paraffin-embedded samples were assessed with high-coverage genome sequencing on the Illumina NextSeq 500 platform using a customized gene panel set covering the coding region of 130 genes. This revealed several notable genomic alterations, including mutations of DICER1 (6 tumors) and KMT2D (also known as MLL2; 5 tumors)-which are frequently recurrent and mutually exclusive molecular events for IO-MEPL. Non-recurrent mutations in the cancer-associated genes BRCA2, BRCA1, NOTCH2, CDH1, and GSE1 were also identified. IO-MEPL samples harboring a DICER1 mutation disclosed few chromosomal alterations and formed a separate DNA methylation cluster, indicating potential differences in genetic and epigenetic events arising perhaps from the presence of this aberration in the tumor genome. The high proportion of recurrent somatic DICER1 and KMT2D mutations in this series of sporadic IO-MEPL points to their likely important roles in the molecular pathogenesis of these rare embryonal tumors, and perhaps suggests the existence of distinct molecular variants of IO-MEPL. Although the precise role of these recurrent mutations in the development of IO-MEPL, and their relationship to pro-oncogenic molecular mechanisms, have yet to be determined, unraveling their roles could eventually be exploited for nonsurgical therapies of these neoplasms. PMID- 26841699 TI - [Antibacterial activity of natural compounds - essential oils]. AB - Since the problem of bacterial resistance has become a serious problem worldwide, it was necessary to search for new active substances that can overcome the problem and enhance the treatment efficacy of bacterial infections. Numerous plant-derived essential oils exhibited significant antibacterial activities. This review aimed to summarize the most promising essential oils that exhibited remarkable antibacterial activities against various bacterial infections, including staphylococcal infections, Helicobacter pylori infections, skin infections, tuberculosis infection and dental bacterial infection. The synergy effect of essential oils in combination with antibiotics, as well as their role in the treatment of bacterial infections have been discussed. Essential oils can be used as models for further studies in vivo and clinical trials. PMID- 26841700 TI - [Cholinergic system of the heart]. AB - The cholinergic system of the heart can be either of neuronal or non-neuronal origin. The neuronal cholinergic system in the heart is represented by preganglionic parasympathetic pathways, intracardiac parasympathetic ganglia and postganglionic parasympathetic neurons projecting to the atria, SA node and AV node. The non-neuronal cholinergic system consists of cardiomyocytes that have complete equipment for synthesis and secretion of acetylcholine. Current knowledge suggests that the non-neuronal cholinergic system in the heart affects the regulation of the heart during sympathetic activation. The non-neuronal cholinergic system of the heart plays also a role in the energy metabolism of cardimyocites. Acetylcholine of both neuronal and non-neuronal origin acts in the heart through muscarinic and nicotinic receptors. The effect of acetylcholine in the heart is terminated by cholinesterases acetylcholinesterase and butyrylcholinesterase. Recently, papers suggest that the increased cholinergic tone in the heart by cholinesterase inhibitors has a positive effect on some cardiovascular disorders such as heart failure. For this reason, the cholinesterase inhibitors might be used in the treatment of certain cardiovascular disorders in the future. PMID- 26841702 TI - Synthesis and Functionalization of Symmetrical 2,5-Diaryl Fulleropyrrolidines: Ferric Perchlorate-Mediated One-Step Reaction of [60]Fullerene with Arylmethanamines. AB - A series of scarce N-unsubstituted 2,5-diaryl fulleropyrrolidines as cis isomers could be prepared via the facile one-step reaction of [60]fullerene with N unsubstituted arylmethanamines promoted by cheap and easily available ferric perchlorate. Nevertheless, the reaction of N-substituted arylmethanamines with [60]fullerene under the same conditions gave different experimental results. N Methylbenzylamine formed N-methyl 2,5-diphenyl fulleropyrrolidine as a trans isomer, and N,N-dibenzylamine unexpectedly afforded the N-unsubstituted 2,5 diphenyl fulleropyrrolidine as a cis isomer. Intriguingly, high stereoselectivity for all 2,5-diaryl fulleropyrrolidines could be observed although both cis and trans isomers were possibly formed. N-Unsubstituted fulleropyrrolidine could be further converted to N-substituted fulleropyrrolidines under the assistance of an acid chloride or an isocyanate. A possible reaction pathway leading to 2,5-diaryl fulleropyrrolidines is also proposed. PMID- 26841701 TI - The RNA helicase DHX34 functions as a scaffold for SMG1-mediated UPF1 phosphorylation. AB - Nonsense-mediated decay (NMD) is a messenger RNA quality-control pathway triggered by SMG1-mediated phosphorylation of the NMD factor UPF1. In recent times, the RNA helicase DHX34 was found to promote mRNP remodelling, leading to activation of NMD. Here we demonstrate the mechanism by which DHX34 functions in concert with SMG1. DHX34 comprises two distinct structural units, a core that binds UPF1 and a protruding carboxy-terminal domain (CTD) that binds the SMG1 kinase, as shown using truncated forms of DHX34 and electron microscopy of the SMG1-DHX34 complex. Truncation of the DHX34 CTD does not affect binding to UPF1; however, it compromises DHX34 binding to SMG1 to affect UPF1 phosphorylation and hence abrogate NMD. Altogether, these data suggest the existence of a complex comprising SMG1, UPF1 and DHX34, with DHX34 functioning as a scaffold for UPF1 and SMG1. This complex promotes UPF1 phosphorylation leading to functional NMD. PMID- 26841703 TI - Evaluation of Disaster Preparedness Based on Simulation Exercises: A Comparison of Two Models. AB - OBJECTIVE: The objective of this study was to highlight 2 models, the Hospital Incident Command System (HICS) and the Disaster Management Indicator model (DiMI), for evaluating the in-hospital management of a disaster situation through simulation exercises. METHODS: Two disaster exercises, A and B, with similar scenarios were performed. Both exercises were evaluated with regard to actions, processes, and structures. After the exercises, the results were calculated and compared. RESULTS: In exercise A the HICS model indicated that 32% of the required positions for the immediate phase were taken under consideration with an average performance of 70%. For exercise B, the corresponding scores were 42% and 68%, respectively. According to the DiMI model, the results for exercise A were a score of 68% for management processes and 63% for management structure (staff skills). In B the results were 77% and 86%, respectively. CONCLUSIONS: Both models demonstrated acceptable results in relation to previous studies. More research in this area is needed to validate which of these methods best evaluates disaster preparedness based on simulation exercises or whether the methods are complementary and should therefore be used together. (Disaster Med Public Health Preparedness. 2016;10:544-548). PMID- 26841704 TI - Intake of bean sprouts influences melatonin and antioxidant capacity biomarker levels in rats. AB - Melatonin is an endogenous antioxidant hormone, which reduces with ageing and the low levels are associated with some chronic diseases. Germination of legumes increases the plant levels of melatonin, making sprouts a suitable food source of this hormone. However, information on its bioavailability after consumption is lacking. We aimed to evaluate in rats the effect of kidney bean sprout intake on the plasma levels of melatonin and metabolically related compounds (serotonin, 6 sulfatoxymelatonin), total phenolic compounds and total antioxidant capacity. In addition, we compared the plasma bioavailability derived from kidney bean sprouts versus synthetic melatonin intake. Kidney beans were germinated for 6 days and an extract was prepared in water. Male young Sprague Dawley rats were used; blood and urine samples were obtained before and after 90 min of administration of kidney bean sprout extract via a gavage. The plasmatic melatonin levels increased after sprout ingestion (16%, p < 0.05). This increment correlated with the urinary 6-sulfatoxymelatonin content, the principal biomarker of plasmatic melatonin levels (p < 0.01). Nevertheless, the phenolic compounds and antioxidant capacity levels did not exhibit any significant variation. The comparison of the bioavailability between the melatonin contained in the kidney bean sprouts and in a synthetic solution evidenced slightly higher levels of plasmatic melatonin (17%) in rats fed with the solution of synthetic melatonin. We conclude that kidney bean sprouts could be a good source of dietary melatonin and other bioactive compounds known to have health benefits. PMID- 26841705 TI - Dietary restraint: what's the harm? A review of the relationship between dietary restraint, weight trajectory and the development of eating pathology. AB - Dietary restraint has historically been implicated as a risk factor for the development of eating pathology. Despite existing findings, recent research suggests that many individuals are capable of practicing dietary restraint without negative effects. In order to successfully incorporate the positive aspects of dietary restraint into interventions for healthy weight management, a nuanced examination of the relationship between dietary restraint and resulting eating patterns is necessary. Accordingly, the current review seeks to clarify the existing literature with regard to dietary restraint. First, this review examines the construct of dietary restraint and differentiates dietary restraint from related constructs, such as weight loss dieting. Second, it identifies situations in which dietary restraint has been linked with positive outcomes, such as healthy weight management and prevention of eating pathology. Altogether, it appears that dietary restraint can prove a beneficial strategy for those attempting to control their weight, as it does not relate to increased levels of eating pathology when practiced as part of a well-validated weight management programme. PMID- 26841706 TI - Assessment of nasal mucociliary activity in patients with Behcet's disease. AB - OBJECTIVE: To investigate nasal mucociliary clearance in patients with Behcet's disease. METHODS: Thirty patients with Behcet's disease, diagnosed on the basis of criteria defined by the International Study Group for Behcet's Disease, and 30 healthy individuals were recruited. In both groups, individuals with conditions that could affect nasal mucociliary clearance were excluded. Nasal mucociliary clearance time was evaluated using saccharin tests. The time between placement of a saccharin tablet and the tasting of the saccharin was measured and recorded as the saccharin clearance time. RESULTS: The mean nasal mucociliary clearance time was significantly longer in the Behcet's disease patients than in the control subjects (p < 0.001). Furthermore, there was a positive correlation between Behcet's disease duration and nasal mucociliary clearance time (p < 0.001, r = 0.882). CONCLUSION: The results suggest that nasal mucociliary clearance time is longer in Behcet's disease patients than in control subjects, and is positively correlated with disease duration. PMID- 26841707 TI - How does the tree root microbiome assemble? Influence of ectomycorrhizal species on Pinus sylvestris root bacterial communities. PMID- 26841708 TI - Tensile Characterization of Single-Walled Carbon Nanotubes with Helical Structural Defects. AB - Recently, evidence was presented that certain single-walled carbon nanotubes (SWNTs) possess helical defective traces, exhibiting distinct cleaved lines, yet their mechanical characterization remains a challenge. On the basis of the spiral growth model of SWNTs, here we present atomic details of helical defects and investigate how the tensile behaviors of SWNTs change with their presence using molecular dynamics simulations. SWNTs have exhibited substantially lower tensile strength and strain than theoretical results obtained from a seamless tubular structure, whose physical origin cannot be explained either by any known SWNT defects so far. We find that this long-lasting puzzle could be explained by assuming helical defects in SWNTs, exhibiting excellent agreement with experimental observation. The mechanism of this tensile process is elucidated by analyzing atomic stress distribution and evolution, and the effects of the chirality and diameter of SWNTs on this phenomenon are examined based on linear elastic fracture mechanics. This work contributes significantly to our understanding of the growth mechanism, defect hierarchies, and mechanical properties of SWNTs. PMID- 26841709 TI - Multifunctional Nanocarpets for Cancer Theranostics: Remotely Controlled Graphene Nanoheaters for Thermo-Chemosensitisation and Magnetic Resonance Imaging. AB - A new paradigm in cancer theranostics is enabled by safe multifunctional nanoplatform that can be applied for therapeutic functions together with imaging capabilities. Herein, we develop a multifunctional nanocomposite consisting of Graphene Oxide-Iron Oxide -Doxorubicin (GO-IO-DOX) as a theranostic cancer platform. The smart magnetic nanoplatform acts both as a hyperthermic agent that delivers heat when an alternating magnetic field is applied and a chemotherapeutic agent in a cancer environment by providing a pH-dependent drug release to administer a synergistic anticancer treatment with an enhanced T2 contrast for MRI. The novel GO-IO-DOX nanocomposites were tested in vitro and were observed to exhibit an enhanced tumoricidal effect through both hyperthermia and cancer cell-specific DOX release along with an excellent MRI performance, enabling a versatile theranostic platform for cancer. Moreover the localized antitumor effects of GO-IO-DOX increased substantially as a result of the drug sensitization through repeated application of hyperthermia. PMID- 26841710 TI - Nonadherence to Antihypertensive Medication Among Hypertensive Adults in the United States?HealthStyles, 2010. AB - Nonadherence, or not taking medications as prescribed, to antihypertensive medications has been associated with uncontrolled hypertension. The authors analyzed data from HealthStyles 2010 to assess medication nonadherence among adults with hypertension. The overall prevalence of hypertension was 27.4% and the prevalence of nonadherence was 30.5% among hypertensive adult respondents. Nonadherence rates were highest among younger adults (aged 18-44 years), Hispanics, those who reported lowest annual income (<$25,000), and those who reported depression. The most common reason stated for nonadherence was "I cannot afford the medication" (35.1%). A multivariate logistic regression model showed age, race, and household income to be associated with nonadherence. These findings suggest that certain subgroups are more likely to report barriers to adherence. Interventions to support the management of hypertension should consider the identification of certain at-risk subgroups and utilize community and clinical evidenced-based resources to improve long-term control. PMID- 26841711 TI - One-step Preparation of Nanoarchitectured TiO2 on Porous Al as Integrated Anode for High-performance Lithium-ion Batteries. AB - Titanium dioxide (TiO2) is an attractive anode material for energy storage devices due to its low-volume-change and high safety. However, TiO2 anodes usually suffer from poor electrical and ionic conductivity, thus causing dramatic degradation of electrochemical performance at rapid charge/discharge rates, which has hindered its use in energy storage devices. Here, we present a novel strategy to address this main obstacle via using nanoarchitectured TiO2 anode consisting of mesoporous TiO2 wrapped in carbon on a tunnel-like etched aluminum substrate prepared by a simple one-step approach. As a result of this nanoarchitecture arrangement, the anode exhibits excellent rate performance and superior cyclability. A rate up to 100 C is achieved with a high specific capacity of about 95 mA h g(-1), and without apparent decay after 8,000 cycles. PMID- 26841712 TI - [Title Page - Paraganglioma of the Head and Neck: Follow-Up of Interventional Procedures with CEUS]. PMID- 26841713 TI - Accurate and sensitive total genomic DNA methylation analysis from sub-nanogram input with embedded SERS nanotags. AB - Sensitive and accurate total genomic DNA methylation analysis was demonstrated by surface-enhanced Raman scattering (SERS) via embedded internal SERS nanotags. The assay was sensitive to 0.2 ng input DNA while differentiating as low as 6.25% changes in DNA methylation. The method could also successfully differentiate cells before and after de-methylating drug-treatment and between tumor and normal biopsies. PMID- 26841714 TI - Distinct molecular signatures of mild extrinsic and intrinsic atopic dermatitis. AB - Atopic dermatitis (AD) is a common inflammatory skin disease with underlying defects in epidermal function and immune responses. In this study, we used microarray analysis to investigate differences in gene expression in lesional skin from patients with mild extrinsic or intrinsic AD compared to skin from healthy controls and from lesional psoriasis skin. The primary aim was to identify differentially expressed genes involved in skin barrier formation and inflammation, and to compare our results with those reported for patients with moderate and severe AD. In contrast to severe AD, expression of the majority of genes associated with skin barrier formation was unchanged or upregulated in patients with mild AD compared to normal healthy skin. Among these, no significant differences in the expression of filaggrin (FLG) and loricrin at both mRNA and protein level were found in lesional skin from patients with mild AD, despite the presence of heterozygous FLG mutations in the majority of patients with mild extrinsic AD. Several inflammation-associated genes such as S100A9, MMP12, CXCL10 and CCL18 were highly expressed in lesional skin from patients with mild psoriasis and were also increased in patients with mild extrinsic and intrinsic AD similar to previous reports for severe AD. Interestingly, expression of genes involved in inflammatory responses in intrinsic AD resembled that of psoriasis more than that of extrinsic AD. Overall, differences in expression of inflammation-associated genes found among patients with mild intrinsic and extrinsic AD correlated with previous findings for patients with severe intrinsic and extrinsic AD. PMID- 26841715 TI - Interaction effects of in-hospital rehabilitation and the use of community-based services after hospital discharge on patients' subsequent functional abilities. AB - BACKGROUND: Patients' functional abilities after hospital discharge are influenced by rehabilitation during their hospital stay and their use of community-based services after hospital discharge. This study examined the interaction between rehabilitation during hospital stay, the use of community based rehabilitation and non-rehabilitation services and their influence on patients' subsequent functional abilities. METHODS: This cohort study included 509 inpatients who underwent rehabilitation between 2008 and 2011 in Japan. Participants were categorized into 2 groups based on their condition: stroke and other. Interaction effects between the change in Functional Independence Measure (FIM) and the use of community-based rehabilitation and non-rehabilitation services on patients' subsequent functional abilities were estimated by sequential linear regression analyses in which the dependent variable was the FIM score 3 months after hospital discharge. RESULTS: A significant interaction between the change in FIM and the use of community-based rehabilitation or non rehabilitation services after hospital discharge was observed among stroke and other patients. CONCLUSION: Rehabilitation during hospital stay and the use of community-based rehabilitation or non-rehabilitation services interacted to influence the subsequent functional abilities of patients discharged home. These findings may be useful for maintaining patients' functional abilities after hospital discharge. PMID- 26841716 TI - Comparison of Antiepileptic Approaches in Treatment of Benzodiazepine Nonresponsive Status Epilepticus. AB - AIMS: Status epilepticus and seizure clusters are common neurological emergencies. The purpose of this monocentric, retrospective cohort study was to comparatively assess different antiepileptic approaches in the treatment of status epilepticus and seizure clusters, which were nonresponsive to benzodiazepines. METHODS: We reviewed medical records of 66 patients, who were treated for status epilepticus or seizure clusters in the Department of Neurology at the University of the Saarland between January 2007 and July 2012, and failed to respond to benzodiazepines with the equivalent dosage of at least 20 mg of diazepam. As endpoints, we analyzed both the effectiveness of lacosamide, levetiracetam, valproic acid, and phenytoin used as second- and third-line therapy, and the Glasgow Outcome Scale at day 7. RESULTS: Sixty-one (92.4%) of the patients had status epilepticus, and 5 (7.6%) had seizure clusters. The compared drugs were equally effective in terminating seizures. There was also no significant difference in the Glasgow Outcome Scale (P = 0.60) after 7 days. CONCLUSION: Our data support the use of the modern antiepileptic treatment strategies, such as levetiracetam, valproic acid, and lacosamide in the treatment of status epilepticus and seizure clusters. PMID- 26841717 TI - A microbial transformation using Bacillus subtilis B7-S to produce natural vanillin from ferulic acid. AB - Bacillus subtilis strain B7-S screened from18 strains is an aerobic, endospore forming, model organism of Gram-positive bacteria which is capable to form vanillin during ferulic acid bioconversion. The bioconversion of ferulic acid to vanillin by Bacillus subtilis B7-S (B. subtilis B7-S) was investigated. Based on our results, the optimum bioconversion conditions for the production of vanillin by B. subtilis B7-S can be summarized as follows: temperature 35 degrees C; initial pH 9.0; inoculum volume 5%; ferulic acid concentration 0.6 g/L; volume of culture medium 20%; and shaking speed 200 r/min. Under these conditions, several repeated small-scale batch experiments showed that the maximum conversion efficiency was 63.30% after 3 h of bioconversion. The vanillin products were confirmed by spectral data achieved from UV-vis, inductively coupled plasma atomic emission spectroscope (ICP-AES) and Fourier transform infrared spectrometer (FT-IR) spectra. Scanning electron microscopy (SEM) and transmission electron spectroscopy (TEM) results confirmed that the cell surface of B. subtilis plays a role in the induction of ferulic acid tolerance. These results demonstrate that B. subtilis B7-S has the potential for use in vanillin production through bioconversion of ferulic acid. PMID- 26841719 TI - A highly active Pd-P nanoparticle electrocatalyst for enhanced formic acid oxidation synthesized via stepwise electroless deposition. AB - A highly active Pd-P nanoparticle electrocatalyst for formic acid oxidation was synthesized using NaH2PO2 as the reducing agent. The Pd-P nanoparticles were amorphous and exhibited higher specific and mass activity values compared to commercial Pd/C electrocatalyts and reported literature values. Furthermore, the Pd-P nanoparticles were found to be more durable than Pd/C electrocatalyts. PMID- 26841718 TI - Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology. AB - Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin's molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally verified the interactions between metformin and our top-ranked kinase targets. Notably, kinases, particularly SGK1 and EGFR were identified as key molecular targets of metformin. Subsequently, we linked these putative binding targets to genes that do not directly bind to metformin but whose expressions are altered by metformin through protein-protein interactions, and identified network biomarkers of phenotypic response of metformin. The molecular targets and the key nodes in genetic networks are largely consistent with the existing experimental evidence. Their interactions can be affected by the observed cancer mutations. This study will shed new light into repurposing metformin for safe, effective, personalized therapies. PMID- 26841721 TI - Chemical derivatization for forensic drug analysis by GC- and LC-MS. AB - Utilizing chemical derivatization (CD) to improve gas chromatographic (GC) and GC mass spectrometric (MS) analysis of drugs has been abundantly studied and widely practiced, while in liquid chromatography (LC) and LC-MS, application of CD approaches is still at an early stage. Silylation, acylation, and alkylation are common CD reactions, long adopted by GC and GC-MS (including GC-MS/MS) methodologies, to improve analytes' stability and/or to optimize their extraction/separation and detection efficiencies. Highly polar and nonvolatile analytes are not amenable to GC-MS analysis without the CD step; however, CD can improve LC-MS analysis of highly polar analytes, especially those with low molecular weights. Many CD reagents developed for GC and GC-MS applications are also effective in LC-MS. Other CD reagents are developed for LC-MS to enhance analytes' performance under electrospray and atmospheric pressure ionization sources. Certain CD reagents are designed to facilitate analytes' fragmentation (upon collision-induced dissociation) in generating intense product ions for sensitive MS/MS detection. In this review, various CD reagents, reaction types, and application examples are presented and discussed, with emphases on GC-MS and LC-MS analysis of drugs of abuse. PMID- 26841720 TI - Mortality from trauma haemorrhage and opportunities for improvement in transfusion practice. AB - BACKGROUND: The aim of this study was to describe the prevalence, patterns of blood use and outcomes of major haemorrhage in trauma. METHODS: This was a prospective observational study from 22 hospitals in the UK, including both major trauma centres and smaller trauma units. Eligible patients received at least 4 units of packed red blood cells (PRBCs) in the first 24 h of admission with activation of the massive haemorrhage protocol. Case notes, transfusion charts, blood bank records and copies of prescription/theatre charts were accessed and reviewed centrally. Study outcomes were: use of blood components, critical care during hospital stay, and mortality at 24 h, 30 days and 1 year. Data were used to estimate the national trauma haemorrhage incidence. RESULTS: A total of 442 patients were identified during a median enrolment interval of 20 (range 7-24) months. Based on this, the national incidence of trauma haemorrhage was estimated to be 83 per million. The median age of patients in the study cohort was 38 years and 73.8 per cent were men. The incidence of major haemorrhage increased markedly in patients aged over 65 years. Thirty-six deaths within 24 h of admission occurred within the first 3 h. At 24 h, 79 patients (17.9 per cent) had died, but mortality continued to rise even after discharge. Patients who received a cumulative ratio of fresh frozen plasma to PRBCs of at least 1 : 2 had lower rates of death than those who received a lower ratio. There were delays in administration of blood. Platelets and cryoprecipitate were either not given, or transfused well after initial resuscitation. CONCLUSION: There is a high burden of trauma haemorrhage that affects all age groups. Research is required to understand the reasons for death after the first 24 h and barriers to timely transfusion support. PMID- 26841722 TI - International trends in alcohol and drug use among vehicle drivers. AB - Trends in the use of alcohol and drugs among motor vehicle drivers in Australia, Brazil, Norway, Spain, and the United States have been reviewed. Laws, regulations, enforcement, and studies on alcohol and drugs in biological samples from motor vehicle drivers in general road traffic and fatal road traffic crashes (RTCs) are discussed. Roadside surveys showed a reduction of drunk driving over time in the studied countries; however, the pattern varied within and between different countries. The reduction of alcohol use may be related to changes in road traffic laws, public information campaigns, and enforcement, including implementation of random breath testing or sobriety checkpoints. For non-alcohol drugs, the trend in general road traffic is an increase in use. However, drugs were not included in older studies; it is therefore impossible to assess the trends over longer time periods. Data from the studied countries, except Brazil, have shown a significant decrease in fatal RTCs per 100,000 inhabitants over the last decades; from 18.6 to 4.9 in Australia, 14.5 to 2.9 in Norway, 11.1 to 3.6 in Spain, and 19.3 to 10.3 in the United States. The number of alcohol-related fatal RTCs also decreased during the same time period. The proportion of fatal RTCs related to non-alcohol drugs increased, particularly for cannabis and stimulants. A general challenge when comparing alcohol and drug findings in biological samples from several countries is connected to differences in study design, particularly the time period for performing roadside surveys, biological matrix types, drugs included in the analytical program, and the cutoff limits used for evaluation of results. For RTC fatalities, the cases included are based on the police requests for legal autopsy or drug testing, which may introduce a significant selection bias. General comparisons between high-income countries and low- and middle-income countries as well as a discussion of possible future trends are included. PMID- 26841723 TI - Erratum to: Temperature-induced variation in gene expression burst size in metazoan cells. PMID- 26841724 TI - Nodular morphoea: a first case associated with linear morphoea. PMID- 26841725 TI - Regulating NKX3.1 stability and function: Post-translational modifications and structural determinants. AB - BACKGROUND: The androgen-regulated homeodomain transcription factor NKX3.1 plays roles in early prostate development and functions as a prostate-specific tumor suppressor. Decreased expression of NKX3.1 protein is common in primary prostate cancer. Discordance between NKX3.1 mRNA and protein levels during prostate carcinogenesis suggested a key role for post-transcriptional modifications in regulating NKX3.1 protein levels in prostate epithelial cells. Subsequent studies revealed NKX3.1 to be modified post-translationally at multiple sites. METHODS: We reviewed published literature to identify and summarize post-translational modifications and structural elements critical in regulating NKX3.1 stability and levels in prostate epithelial cells. RESULTS: NKX3.1 is modified post translationally at multiple sites by different protein kinases. These modifications together with several structural determinants were identified to play an important role in NKX3.1 stability and biology. CONCLUSIONS: In this review, we provide a comprehensive overview of the known post-translational modifications and structural features that impact NKX3.1. Defining factors that regulate NKX3.1 in prostate epithelial cells will extend our understanding of molecular changes that may contribute to prostate cancer initiation and progression. PMID- 26841726 TI - Impacts of Pristine and Transformed Ag and Cu Engineered Nanomaterials on Surficial Sediment Microbial Communities Appear Short-Lived. AB - Laboratory-based studies have shown that many soluble metal and metal oxide engineered nanomaterials (ENM) exert strong toxic effects on microorganisms. However, laboratory-based studies lack the complexity of natural systems and often use "as manufactured" ENMs rather than more environmentally relevant transformed ENMs, leaving open the question of whether natural ligands and seasonal variation will mitigate ENM impacts. Because ENMs will accumulate in subaquatic sediments, we examined the effects of pristine and transformed Ag and Cu ENMs on surficial sediment microbial communities in simulated freshwater wetlands. Five identical mesocosms were dosed through the water column with either Ag(0), Ag2S, CuO or CuS ENMs (nominal sizes of 4.67 +/- 1.4, 18.1 +/- 3.2, 31.1 +/- 12, and 12.4 +/- 4.1, respectively) or Cu(2+). Microbial communities were examined at 0, 7, 30, 90, 180, and 300 d using qPCR and high-throughput 16S rRNA gene sequencing. Results suggest differential short-term impacts of Ag(0) and Ag2S, similarities between CuO and CuS, and differences between Cu ENMs and Cu(2+). PICRUSt-predicted metagenomes displayed differential effects of Ag treatments on photosynthesis and of Cu treatments on methane metabolism. By 300 d, all metrics pointed to reconvergence of ENM-dosed mesocosm microbial community structure and composition, suggesting that the long-term microbial community impacts from a pulse of Ag or Cu ENMs are limited. PMID- 26841727 TI - Favorable Waitlist and Posttransplant Outcomes in Children and Adolescent Patients Supported With Durable Continuous-Flow Ventricular Assist Devices. AB - Pediatric centers are implanting durable adult continuous-flow ventricular assist devices (CFVADs) in children who are smaller than the industry-recommended size. Waitlist and posttransplant outcomes data in pediatric patients supported with CFVADs as a bridge to transplant are limited. We analyzed the United Network of Organ Sharing and Organ Procurement and Transplantation Network registry to identify patients aged <=18 years with a CFVAD at the time of listing or transplantation. Patients were stratified by body surface area (BSA; >1.5 vs. <=1.5 m(2) ) at time of listing. We identified 138 patients with a durable CFVAD during the listing period (100 with BSA >1.5 m(2) , 38 with BSA <=1.5 m(2) ). Patients with BSA <=1.5 m(2) were more likely to have a noncardiomyopathy diagnosis (18% vs. 4%, p = 0.007) and to be implanted with a centrifugal-flow rather than an axial-flow device (74% vs. 30%, p = 0.001). There was no difference in failure-free waitlist survival between BSA groups (p = 0.99) among patients with a CFVAD at listing. Posttransplantation survival was 100% and 88% at 1 and 5 years, respectively, for the entire cohort and did not differ by BSA group (p = 0.99). Consequently, waitlist and posttransplant outcomes are favorable for pediatric CFVAD recipients. Small patients (<=1.5 m(2) ) had pre- and posttransplant outcomes similar to those of larger patients that met the industry-recommended size for implantation. PMID- 26841728 TI - The downfalls of BMI-focused policies. PMID- 26841729 TI - Misclassification of cardiometabolic health when using body mass index categories in NHANES 2005-2012. AB - The United States Equal Employment Opportunity Commission has proposed rules allowing employers to penalize employees up to 30% of health insurance costs if they fail to meet 'health' criteria, such as reaching a specified body mass index (BMI). Our objective was to examine cardiometabolic health misclassifications given standard BMI categories. Participants (N=40 420) were individuals aged 18+ in the nationally representative 2005-2012 National Health and Nutrition Examination Survey. Using the blood pressure, triglyceride, cholesterol, glucose, insulin resistance and C-reactive protein data, population frequencies/percentages of metabolically healthy versus unhealthy individuals were stratified by BMI. Nearly half of overweight individuals, 29% of obese individuals and even 16% of obesity type 2/3 individuals were metabolically healthy. Moreover, over 30% of normal weight individuals were cardiometabolically unhealthy. There was no significant race-by-BMI interaction, but there was a significant gender-by-BMI interaction, F(4,64)=3.812, P=0.008. Using BMI categories as the main indicator of health, an estimated 74 936 678 US adults are misclassified as cardiometabolically unhealthy or cardiometabolically healthy. Policymakers should consider the unintended consequences of relying solely on BMI, and researchers should seek to improve diagnostic tools related to weight and cardiometabolic health. PMID- 26841732 TI - Hepatitis C: cost of lost opportunities. PMID- 26841731 TI - Unproductive exocytosis. AB - Regulated exocytosis is a multistage process involving a merger between the vesicle and the plasma membrane, leading to the formation of a fusion pore, a channel, through which secretions are released from the vesicle to the cell exterior. A stimulus may influence the pore by either dilating it completely (full-fusion exocytosis) or mediating a reversible closure (transient exocytosis). In neurons, these transitions are short-lived and not accessible for experimentation. However, in some neuroendocrine cells and astrocytes, initial fusion pores may reopen several hundred times, indicating their stability. Frequently, these pores are too narrow to pass luminal molecules to the extracellular space (unproductive exocytosis), but their diameter can dilate upon stimulation. To explain the stability of the initial narrow fusion pores, anisotropic membrane constituents with a non-axisymmetric shape were proposed to accumulate in the fusion pore membrane. Although the nature of these is unclear, they may consist of lipids and proteins, including SNAREs, which may facilitate and regulate the pre- and post-fusional stages of exocytosis. This review highlights models and experimental studies revealing mechanisms of fusion pore stabilization in a narrow, release unproductive state. The fusion pore is a channel that forms when the vesicle and the plasma membranes merge, and mediates the release of secretions from the vesicle lumen to the cell exterior. Frequently, these pores are too narrow to pass molecules to the extracellular space. Anisotropic membrane constituents with a non-axisymmetric shape were proposed to accumulate in the fusion pore membrane. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015). PMID- 26841730 TI - Stochastic dynamic study of optical transition properties of single GFP-like molecules. AB - Due to high fluctuations and quantum uncertainty, the processes of single molecules should be treated by stochastic methods. To study fluorescence time series and their statistical properties, we have applied two stochastic methods, one of which is an analytic method to study the off-time distributions of certain fluorescence transitions and the other is Gillespie's method of stochastic simulations. These methods have been applied to study the optical transition properties of two single-molecule systems, GFPmut2 and a Dronpa-like molecule, to yield results in approximate agreement with experimental observations on these systems. Rigorous oscillatory time series of GFPmut2 before it unfolds in the presence of denaturants have not been obtained based on the stochastic method used, but, on the other hand, the stochastic treatment puts constraints on the conditions under which such oscillatory behavior is possible. Furthermore, a sensitivity analysis is carried out on GFPmut2 to assess the effects of transition rates on the observables, such as fluorescence intensities. PMID- 26841734 TI - Health at a Glance: worth a second look. PMID- 26841733 TI - Safe (space) travels. PMID- 26841735 TI - HPV vaccination for victims of childhood sexual abuse. PMID- 26841737 TI - Lesotho's controversial public-private partnership project. PMID- 26841738 TI - Doctors silenced over Australia's immigration centres. PMID- 26841739 TI - William Harvey's demonstration rod. PMID- 26841740 TI - The time of our lives. PMID- 26841741 TI - The rights of children arriving in Europe. PMID- 26841742 TI - Standing up for refugees. PMID- 26841743 TI - Palliative care in complex humanitarian crisis responses. PMID- 26841744 TI - Post-authorisation assessment of orphan drugs. PMID- 26841745 TI - Global surgery and the dilemma for obstetricians. PMID- 26841746 TI - Long-term effects of lithium on renal function. PMID- 26841747 TI - Letter from the future surgeons of 2030. PMID- 26841748 TI - Long-term effects of lithium on renal function. PMID- 26841749 TI - Long-term effects of lithium on renal function. PMID- 26841750 TI - Long-term effects of lithium on renal function. PMID- 26841752 TI - Department of Error. PMID- 26841751 TI - Long-term effects of lithium on renal function--Authors' reply. PMID- 26841753 TI - Department of Error. PMID- 26841755 TI - C-terminal acidic domain of histone chaperone human NAP1 is an efficient binding assistant for histone H2A-H2B, but not H3-H4. AB - Nucleosome assembly protein 1 (NAP1) binds both the (H3-H4)2 tetramer and two H2A H2B dimers, mediating their sequential deposition on DNA. NAP1 contains a C terminal acidic domain (CTAD) and a core domain that promotes dimer formation. Here, we have investigated the roles of the core domain and CTAD of human NAP1 in binding to H2A-H2B and H3-H4 by isothermal calorimetry and native mass spectrometry and compared them with the roles of yeast NAP1. We show that the hNAP1 and yNAP1 dimers bind H2A-H2B by two different modes: a strong endothermic interaction and a weak exothermic interaction. A mutant hNAP1, but not yNAP1, dimer lacking CTAD loses the exothermic interaction and shows greatly reduced H2A H2B binding activity. The isolated CTAD of hNAP1 binds H2A-H2B only exothermically with relatively stronger binding as compared with the exothermic interaction observed for the full-length hNAP1 dimer. Thus, the two CTADs in the hNAP1 dimer seem to provide binding assistance for the strong endothermic interaction of the core domain with H2A-H2B. By contrast, in the relatively weaker binding of hNAP1 to H3-H4 as compared with yNAP1, CTAD of hNAP1 has no significant role. To our knowledge, this is the first distinct role identified for the hNAP1 CTAD. PMID- 26841756 TI - Increased fucosyl glycoconjugate by Mycoplasma hyopneumoniae enhances adherences of Pasteurella multocida type A in the ciliated epithelial cells of the respiratory tract. AB - BACKGROUND: The objective of this study was to elucidate the pathogenic mechanisms of how Mycoplasma hyopneumoniae enhances secondary Pasteurella multocida type A infection which leads to porcine enzootic pneumonia in infected pigs. Sixteen pigs were experimentally infected with M. hyopneumoniae and then euthanized at 7, 14, 21 and 28 days post inoculation. In situ hybridization for M. hyopneumoniae DNA and Ulex europaeus agglutinin-I (UEA-I) lectin histochemistry for fucosyl glycoconjugate, was performed in serial lung sections to determine alteration of fucosyl glycoconjugate in M. hyopneumoniae-infected bronchial and bronchiolar epithelium. Bacterial overlay assay was performed to determine the affinity of P. multocida type A with L-fucose. RESULTS: The luminal surface of bronchial and bronchiolar epithelial cells that were stained with UEA I always showed hybridization signals for M. hyopneumoniae but it was negative in the unaffected parts of the lung from M. hyopneumoniae-infected pigs and in lung from negative control pigs. Colocalization of M. hyopneumoniae and UEA-I was especially prominent in the luminal surface of bronchial and bronchiolar epithelial cells in serial section of lung. The mean number of M. hyopneumoniae positive cells correlated with the mean number of UEA-I-positive cells in lungs from infected pigs throughout the experiment. All eight P. multocida type A isolates from naturally occurring enzootic pneumonia, bound strongly at levels of 2 MUg and 5 MUg of L-fucose. CONCLUSIONS: The results of the present study demonstrate that M. hyopneumoniae increases the L-fucose composition to enhance adherence of P. multocida type A to the bronchial and bronchiolar epithelial cells. PMID- 26841759 TI - The role of mass transport in protein crystallization. AB - Mass transport takes place within the mesoscopic to macroscopic scale range and plays a key role in crystal growth that may affect the result of the crystallization experiment. The influence of mass transport is different depending on the crystallization technique employed, essentially because each technique reaches supersaturation in its own unique way. In the case of batch experiments, there are some complex phenomena that take place at the interface between solutions upon mixing. These transport instabilities may drastically affect the reproducibility of crystallization experiments, and different outcomes may be obtained depending on whether or not the drop is homogenized. In diffusion experiments with aqueous solutions, evaporation leads to fascinating transport phenomena. When a drop starts to evaporate, there is an increase in concentration near the interface between the drop and the air until a nucleation event eventually takes place. Upon growth, the weight of the floating crystal overcomes the surface tension and the crystal falls to the bottom of the drop. The very growth of the crystal then triggers convective flow and inhomogeneities in supersaturation values in the drop owing to buoyancy of the lighter concentration depleted solution surrounding the crystal. Finally, the counter-diffusion technique works if, and only if, diffusive mass transport is assured. The technique relies on the propagation of a supersaturation wave that moves across the elongated protein chamber and is the result of the coupling of reaction (crystallization) and diffusion. The goal of this review is to convince protein crystal growers that in spite of the small volume of the typical protein crystallization setup, transport plays a key role in the crystal quality, size and phase in both screening and optimization experiments. PMID- 26841760 TI - Crystal structure of the flavoenzyme PA4991 from Pseudomonas aeruginosa. AB - The locus PA4991 in Pseudomonas aeruginosa encodes an open reading frame that has been identified as essential for the virulence and/or survival of this pathogenic organism in the infected host. Here, it is shown that this gene encodes a monomeric FAD-binding protein of molecular mass 42.2 kDa. The structure of PA4991 was determined by a combination of molecular replacement using a search model generated with Rosetta and phase improvement by a low-occupancy heavy-metal derivative. PA4991 belongs to the GR2 family of FAD-dependent oxidoreductases, comprising an FAD-binding domain typical of the glutathione reductase family and a second domain dominated by an eight-stranded mixed beta-sheet. Most of the protein-FAD interactions are via the FAD-binding domain, but the isoalloxazine ring is located at the domain interface and interacts with residues from both domains. A comparison with the structurally related glycine oxidase and glycerol 3-phosphate dehydrogenase shows that in spite of very low amino-acid sequence identity (<18%) several active-site residues involved in substrate binding in these enzymes are conserved in PA4991. However, enzymatic assays show that PA4991 does not display amino-acid oxidase or glycerol-3-phosphate dehydrogenase activities, suggesting that it requires different substrates for activity. PMID- 26841761 TI - Structural and functional analysis of the RNA helicase Prp43 from the thermophilic eukaryote Chaetomium thermophilum. AB - RNA helicases are indispensable for all organisms in each domain of life and have implications in numerous cellular processes. The DEAH-box RNA helicase Prp43 is involved in pre-mRNA splicing as well as rRNA maturation. Here, the crystal structure of Chaetomium thermophilum Prp43 at 2.9 A resolution is revealed. Furthermore, it is demonstrated that Prp43 from C. thermophilum is capable of functionally replacing its orthologue from Saccharomyces cerevisiae in spliceosomal disassembly assays. PMID- 26841762 TI - Structure of the human histone chaperone FACT Spt16 N-terminal domain. AB - The histone chaperone FACT plays an important role in facilitating nucleosome assembly and disassembly during transcription. FACT is a heterodimeric complex consisting of Spt16 and SSRP1. The N-terminal domain of Spt16 resembles an inactive aminopeptidase. How this domain contributes to the histone chaperone activity of FACT remains elusive. Here, the crystal structure of the N-terminal domain (NTD) of human Spt16 is reported at a resolution of 1.84 A. The structure adopts an aminopeptidase-like fold similar to those of the Saccharomyces cerevisiae and Schizosaccharomyces pombe Spt16 NTDs. Isothermal titration calorimetry analyses show that human Spt16 NTD binds histones H3/H4 with low micromolar affinity, suggesting that Spt16 NTD may contribute to histone binding in the FACT complex. Surface-residue conservation and electrostatic analysis reveal a conserved acidic patch that may be involved in histone binding. PMID- 26841763 TI - Crystal structure of microtubule affinity-regulating kinase 4 catalytic domain in complex with a pyrazolopyrimidine inhibitor. AB - Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) is a serine/threonine kinase involved in the phosphorylation of MAP proteins that regulate microtubule dynamics. Abnormal activity of MARK4 has been proposed to contribute to neurofibrillary tangle formation in Alzheimer's disease. The crystal structure of the catalytic and ubiquitin-associated domains of MARK4 with a potent pyrazolopyrimidine inhibitor has been determined to 2.8 A resolution with an Rwork of 22.8%. The overall structure of MARK4 is similar to those of the other known MARK isoforms. The inhibitor is located in the ATP-binding site, with the pyrazolopyrimidine group interacting with the inter-lobe hinge region while the aminocyclohexane moiety interacts with the catalytic loop and the DFG motif, forcing the activation loop out of the ATP-binding pocket. PMID- 26841764 TI - Cloning, expression, purification, crystallization and initial crystallographic analysis of FleN from Pseudomonas aeruginosa. AB - The assembly of bacterial flagella requires the coordinated expression of a large number of genes in a hierarchical manner. These genes code for structural components of flagella, regulatory components and components that are required for chemotaxis. Stringent spatial and numerical control of flagella biosynthesis is essential for promoting motility and pathogenesis in bacteria. These genes are regulated at the level of transcription. FleN, a P-loop-containing ATPase, plays an important role in maintaining flagellar number in Pseudomonas aeruginosa. FleN exhibits anti-activator activity against FleQ, the global transcriptional regulator of flagellar genes. In order to gain insights into the regulatory mechanism of flagella synthesis, full-length FleN was crystallized in complex with the nonhydrolyzable ATP analogue beta,gamma-imidoadenosine 5'-triphosphate (AMPPNP) in space group C2221, with unit-cell parameters a = 49.1, b = 206.9, c = 103.3 A. The Matthews coefficient is 2.19 A(3) Da(-1) assuming the presence of two molecules in the asymmetric unit, and the corresponding solvent content is 43.7%. X-ray diffraction data were collected to a minimum Bragg spacing of 2.21 A and crystals of FleN-AMPPNP were prepared with selenomethionine-labelled FleN for ab initio phasing. PMID- 26841765 TI - Crystallographic observation of the movement of the membrane-distal domain of the T7SS core component EccB1 from Mycobacterium tuberculosis. AB - The protein EccB1, a core component of the type VII secretion system (T7SS) of Mycobacterium tuberculosis, has been identified as an ATPase and is essential for the secretion of virulence factors by the ESX-1 system. In a previous study, EccB1 structures were determined in two different conformations. Here, two new conformations are identified and described. These four conformations present snapshots of the swinging movement of the membrane-distal domain A2. The movement of this domain involves conformational changes in two flexible loops (loop A, residues 243-264, and loop B, residues 324-341) which are rich in proline and glycine residues and connect domain A2 to domains C1 and B2. It is proposed that the movement of this domain is related to the ATPase activity of EccB1 and its homologues, as well as to the substrate transport of ESX secretion systems. PMID- 26841758 TI - Protein stability: a crystallographer's perspective. AB - Protein stability is a topic of major interest for the biotechnology, pharmaceutical and food industries, in addition to being a daily consideration for academic researchers studying proteins. An understanding of protein stability is essential for optimizing the expression, purification, formulation, storage and structural studies of proteins. In this review, discussion will focus on factors affecting protein stability, on a somewhat practical level, particularly from the view of a protein crystallographer. The differences between protein conformational stability and protein compositional stability will be discussed, along with a brief introduction to key methods useful for analyzing protein stability. Finally, tactics for addressing protein-stability issues during protein expression, purification and crystallization will be discussed. PMID- 26841766 TI - Crystallization and X-ray diffraction of LGN in complex with the actin-binding protein afadin. AB - Asymmetric stem-cell divisions are fundamental for morphogenesis and tissue homeostasis. They rely on the coordination between cortical polarity and the orientation of the mitotic spindle, which is orchestrated by microtubule pulling motors recruited at the cortex by NuMA-LGN-Galphai complexes. LGN has emerged as a central component of the spindle-orientation pathway that is conserved throughout species. Its domain structure consists of an N-terminal TPR domain associating with NuMA, followed by four GoLoco motifs binding to Galphai subunits. The LGN(TPR) region is also involved in interactions with other membrane-associated proteins ensuring the correct cortical localization of microtubule motors, among which is the junctional protein afadin. To investigate the architecture of LGN(TPR) in complex with afadin, a chimeric fusion protein with a native linker derived from the region of afadin upstream of the LGN binding domain was generated. The fusion protein behaves as a globular monomer in solution and readily crystallizes in the presence of sulfate-containing reservoirs. The crystals diffracted to 3.0 A resolution and belonged to the cubic space group P213, with unit-cell parameter a = 170.3 A. The structure of the engineered protein revealed that the crystal packing is promoted by the coordination of sulfate ions by residues of the afadin linker region and LGN(TPR). PMID- 26841767 TI - Improving diffraction resolution using a new dehydration method. AB - The production of high-quality crystals is one of the major obstacles in determining the three-dimensional structure of macromolecules by X-ray crystallography. It is fairly common that a visually well formed crystal diffracts poorly to a resolution that is too low to be suitable for structure determination. Dehydration has proven to be an effective post-crystallization treatment for improving crystal diffraction quality. Several dehydration methods have been developed, but no single one of them is suitable for all crystals. Here, a new convenient and effective dehydration method is reported that makes use of a dehydrating solution that will not dry out in air for several hours. Using this dehydration method, the resolution of Archaeoglobus fulgidus Cas5a crystals has been increased from 3.2 to 1.95 A and the resolution of Escherichia coli LptA crystals has been increased from <5 to 3.4 A. PMID- 26841768 TI - Pathogenesis comparison between the United States porcine epidemic diarrhoea virus prototype and S-INDEL-variant strains in conventional neonatal piglets. AB - At least two genetically different porcine epidemic diarrhoea virus (PEDV) strains have been identified in the USA: US PEDV prototype and S-INDEL-variant strains. The objective of this study was to compare the pathogenicity differences of the US PEDV prototype and S-INDEL-variant strains in conventional neonatal piglets under experimental infections. Fifty PEDV-negative 5-day-old pigs were divided into five groups of ten pigs each and were inoculated orogastrically with three US PEDV prototype isolates (IN19338/2013, NC35140/2013 and NC49469/2013), an S-INDEL-variant isolate (IL20697/2014), and virus-negative culture medium, respectively, with virus titres of 104 TCID50 ml- 1, 10 ml per pig. All three PEDV prototype isolates tested in this study, regardless of their phylogenetic clades, had similar pathogenicity and caused severe enteric disease in 5-day-old pigs as evidenced by clinical signs, faecal virus shedding, and gross and histopathological lesions. Compared with pigs inoculated with the three US PEDV prototype isolates, pigs inoculated with the S-INDEL-variant isolate had significantly diminished clinical signs, virus shedding in faeces, gross lesions in small intestines, caeca and colons, histopathological lesions in small intestines, and immunohistochemistry staining in ileum. However, the US PEDV prototype and the S-INDEL-variant strains induced similar viraemia levels in inoculated pigs. Whole genome sequences of the PEDV prototype and S-INDEL-variant strains were determined, but the molecular basis of virulence differences between these PEDV strains remains to be elucidated using a reverse genetics approach. PMID- 26841769 TI - Saved from the skip: doctor's action sees hospital art get national recognition. PMID- 26841770 TI - Contribution of Blastocystishominis subtypes and associated inflammatory factors in development of irritable bowel syndrome. AB - Blastocystis hominis with worldwide distribution is a human intestinal protozoa found in all countries. There have been differences in the severity of the pathogenesis of various Blastocystis spp. and a concomitant variation in the plasma concentration of the cytokines in patients with irritable bowel syndrome. In the present study, we aimed to demonstrate the contribution of B. hominis subtypes in the development of irritable bowel syndrome. Stool samples were collected from patients with gastrointestinal disorders. All samples were evaluated through native-lugol method. Total DNA was extracted. A PCR protocol was developed to amplify a specific region of the SSU ribosomal DNA (rDNA) gene. Serum levels of IL-6 and TNF-alpha were determined by immunoassay methods. The ClustalW algorithm was applied to align and blast the nucleotide sequences of the amplified region of the SSU rDNA gene. To evaluate the phylogenetic and molecular evolutionary of the nucleotide sequences, we used the MEGA software. In this study, we found 26 haplotypes of B. hominis in the studied samples which were collectively belong to five subtypes (ST1, ST2 in patients without irritable bowel syndrome vs. ST3 and two unknown subtypes in patients with irritable bowel syndrome). Result of ELISA showed a high level of IL-6 and TNF-alpha in the serum of patients with irritable bowel syndrome. The genetic heterogeneity of B. hominis and the existence of different subtypes of the protozoan in patients with IBS may shed light to the fact that some subtypes of parasites may involve in the pathogenesis of IBS. PMID- 26841771 TI - Genotypic, physiological, and biochemical characterization of potentially pathogenic Acanthamoeba isolated from the environment in Cairo, Egypt. AB - Acanthamoebae are the most common opportunistic amphizoic protozoa that cause life-threatening granulomatous amoebic encephalitis in immunocompromised individuals and sight-threatening amoebic keratitis (AK) in contact lens wearers. The present work aimed to determine the presence of Acanthamoeba isolates in different environmental sources: water, soil, and dust in Cairo, Egypt and to characterize the pathogenic potential of the isolated Acanthamoeba using physiological and biochemical assays as well as determination of the genotypes in an attempt to correlate pathogenicity with certain genotypes. The study included the collection of 22 corneal scrapings from patients complaining of symptoms and signs indicative of acanthamoeba keratitis (AK) and 75 environmental samples followed by cultivation on non-nutrient agar plates preseeded with E. coli. Positive samples for Acanthamoeba were subjected to osmo- and thermo-tolerance assays and zymography analysis. Potentially pathogenic isolates were subjected to PCR amplification using genus-specific primer pair. Isolates were classified at the genotype level based on the sequence analysis of Acanthamoeba 18S rRNA gene (diagnostic fragment 3). The total detection rate for Acanthamoeba in environmental samples was 33.3 %, 31.4 % in water, 40 % in soil, and 20 % in dust samples. Three and two Acanthamoeba isolates from water and soil sources, respectively, had the potential for pathogenicity as they exhibited full range of pathogenic traits. Other 12 isolates were designated as weak potential pathogens. Only ten of the environmental isolates were positive in PCR and were classified by genotype analysis into T4 genotype (70 %), T3 (10 %) and T5 (20 %). Potential pathogens belonged to genotypes T4 (from water) and T5 (from soil) while weak potential pathogens belonged to genotypes T3 (from water) and T4 (from water and soil). Additionally, T7 genotype was isolated from keratitis patients. There is a considerable variation in the response of Acanthamoeba members of the same genotype to pathogenicity indicator assays making correlation of pathogenicity with certain genotypes difficult. Presence of potentially pathogenic Acanthamoeba isolates in habitats related directly to human populations represent a risk for human health. Isolation of Acanthamoeba genotype T7 from AK cases, which is commonly considered as nonpathogenic, might draw the attention to other Acanthamoeba genotypes considered as non pathogenic and reevaluate their role in production of human infections. To our knowledge, this is the first study on the presence and distribution of Acanthamoeba genotypes in the environment, Cairo, Egypt. PMID- 26841772 TI - National and sub-national drinking water fluoride concentrations and prevalence of fluorosis and of decayed, missed, and filled teeth in Iran from 1990 to 2015: a systematic review. AB - Fluoride intake, fluorosis, and dental caries could affect quality of life and disease burden worldwide. As a part of the National and Sub-national Burden of Disease Study (NASBOD) in Iran, we conducted a systematic review to evaluate province-year-specific mean drinking water fluoride concentrations and prevalence of fluorosis and of decayed, missed, and filled teeth (DMFT) in Iran from 1990 to December 2015. We did electronic searches of all English and Persian publications on PubMed, ScienceDirect, Google Scholar, and Iranian databases. Results revealed that the weighted mean drinking water fluoride concentration in Iran from 1990 to 2015 has been about 0.65 +/- 0.38 mg/l. However, based on the WHO guideline value (1.50 mg/l) and the maximum permissible Iranian national fluoride standard (1.40 to 2.40 mg/l depending on the region's climate), there have been some regions in Iran with non-optimum fluoride concentrations in their drinking water (up to 7.0 mg/l). Overall, concentrations have been higher in southern parts of Iran and in some areas of Azerbaijan-e-Gharbi Province in the northwest and lower in the rest of the northwest and central parts of Iran. In addition, some hotspots have been found in Bushehr Province, southwest of Iran. The highest prevalence of dental flourosis has been reported in normal index while the lowest prevalence has been expressed in severe index. The lowest DMFT (about 0.1) was in Arsanjan City in Fars Province, and the highest (about 6.7) was for Najaf Abad City in Isfahan Province. Prevalence of fluorosis has been rather high in studied areas of Iran (e.g. 100 % in Maku City in Azarbaijan-e-Gharbi Province), and there was discrepancy for DMFT, but a lack of studies renders the results inconclusive. Further studies, health education and promotion plans, and evidence-based nutrition programs are recommended. PMID- 26841773 TI - The use of reed canary grass and giant miscanthus in the phytoremediation of municipal sewage sludge. AB - The application of municipal sewage sludge on energy crops is an alternative form of recycling nutrients, food materials, and organic matter from waste. Municipal sewage sludge constitutes a potential source of heavy metals in soil, which can be partially removed by the cultivation of energy crops. The aim of the research was to assess the effect of municipal sewage sludge on the uptake of heavy metals by monocotyledonous energy crops. Sewage sludge was applied at doses of 0, 10, 20, 40, and 60 Mg DM . ha(-1) once, before the sowing of plants. In a 6-year field experiment, the effect of four levels of fertilisation with sewage sludge on the uptake of heavy metals by two species of energy crops, reed canary grass (Phalaris arundinacea L.) of 'Bamse' cultivar and giant miscanthus (Miscanthus * giganteus GREEF et DEU), was analysed. It was established that the increasing doses of sewage sludge had a considerable effect on the increase in biomass yield from the tested plants. Due to the increasing doses of sewage sludge, a significant increase in heavy metals content in the energy crops was recorded. The heavy metal uptake with the miscanthus yield was the highest at a dose of 20 Mg DM . ha(-1), and at a dose of 40 Mg DM . ha(-1) in the case of reed canary grass. Research results indicate that on account of higher yields, higher bioaccumulation, and higher heavy metal uptake, miscanthus can be selected for the remediation of sewage sludge. PMID- 26841775 TI - Characterizing the compositional variation of dissolved organic matter over hydrophobicity and polarity using fluorescence spectra combined with principal component analysis and two-dimensional correlation technique. AB - Dissolved organic matter (DOM) obtained from three leachates with different landfill ages was fractionated, and its compositional variation based on hydrophobicity and polarity was characterized by synchronous fluorescence spectra combined with principal component analysis (PCA) and two-dimensional correlation technique. The results showed that the bulk DOM and its fractions were comprised of tryosine-, tryptophan-, fulvic-, and humic-like substances. Tyrosine-like matter was dominant in the young leachate DOM and its fractions, while tryptophan , fulvic-, and humic-like substances were the main components in the intermediate and old leachate DOMs and their fractions. Tryosine-, tryptophan-, fulvic-, and humic-like substances varied concurrently with the hydrophobicity and polarity. However, the change ratio of these substances was different for the three leachates. Tyrosine-like matter, humic-like materials, and fulvic-like substances were the most sensitive to the hydrophobicity and polarity in the young, intermediate, and old leachates, respectively. Such an integrated approach jointly enhances the characterization of the hydrophobicity- and polarity dependent DOM fractions and provides a promising way to elucidate the environmental behaviors of different DOM species. PMID- 26841774 TI - Wet deposition of persistent organic pollutants (POPs) in Izmir, Turkey. AB - Concentrations of several polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polycyclic aromatic hydrocarbons (PAHs), and polybrominated diphenyl ethers (PBDEs) were measured in precipitation (n = 33) at a suburban site in Izmir, Turkey. Total (dissolved + particle) volume weighted mean (VWM) concentrations for Sigma16PAHs, Sigma18PCBs, Sigma17OCPs, and Sigma7PBDEs were 785, 19.2, 50.5, and 29.6 ng l(-1), respectively. Low molecular weight (LMW) compounds (acenaphthylene, fluorene, phenanthrene) and congeners (PCB-18, 28, and 31) dominated the PAH and PCB concentrations, respectively. For PBDEs, BDE-209, and for OCPs, chlorpyrifos, a currently used pesticide, were the predominant compounds. Annual Sigma7PBDEs flux was 18.74 MUg m(-2) year(-1). PBDE fluxes were mainly in dissolved phase for all congeners except BDE-209 which had comparable proportions in both phases. Annual flux for Sigma16PAHs was 497.4 MUg m(-2) year( 1); higher molecular weight (MW) PAH fluxes had comparable amounts in both phases while lower MW ones were mostly in dissolved phase. Wet deposition fluxes for Sigma18PCBs and Sigma17OCPs were 9.40 and 31.94 MUg m(-2) year(-1), respectively, and they were predominantly in dissolved phase. Wet deposition fluxes were compared to previously measured annual dry deposition fluxes at the study site to determine their relative contributions to annual total (dry particle + wet) deposition. Dry deposition was the major removal mechanism for most of the PAHs and PCBs contributing >80 % to total (wet + dry) deposition. However, both processes were comparable for PBDEs. Wet deposition was the predominant process for some OCPs such as alpha-chlordane, gamma-chlordane, and trans-nonachlor while both processes were comparable for chlorpyrifos and heptachlor epoxide. PMID- 26841776 TI - Organic acids in cloud water and rainwater at a mountain site in acid rain areas of South China. AB - To investigate the chemical characteristics of organic acids and to identify their source, cloud water and rainwater samples were collected at Mount Lu, a mountain site located in the acid rain-affected area of south China, from August to September of 2011 and March to May of 2012. The volume-weighted mean (VWM) concentration of organic acids in cloud water was 38.42 MUeq/L, ranging from 7.45 to 111.46 MUeq/L, contributing to 2.50 % of acidity. In rainwater samples, organic acid concentrations varied from 12.39 to 68.97 MUeq/L (VWM of 33.39 MUeq/L). Organic acids contributed significant acidity to rainwater, with a value of 17.66 %. Formic acid, acetic acid, and oxalic acid were the most common organic acids in both cloud water and rainwater. Organic acids had an obviously higher concentration in summer than in spring in cloud water, whereas there was much less discrimination in rainwater between the two seasons. The contribution of organic acids to acidity was lower during summer than during spring in both cloud water (2.20 % in summer vs 2.83 % in spring) and rainwater (12.24 % in summer vs 19.89 % in spring). The formic-to-acetic acid ratio (F/A) showed that organic acids were dominated by primary emissions in 71.31 % of the cloud water samples and whole rainwater samples. Positive matrix factorization (PMF) analysis determined four factors as the sources of organic acids in cloud water, including biogenic emissions (61.8 %), anthropogenic emissions (15.28 %), marine emissions (15.07 %) and soil emissions (7.85 %). The findings from this study imply an indispensable role of organic acids in wet deposition, but organic acids may have a limited capacity to increase ecological risks in local environments. PMID- 26841777 TI - Evolution of the microbial community of the biofilm in a methane-based membrane biofilm reactor reducing multiple electron acceptors. AB - Previous work documented complete perchlorate reduction in a membrane biofilm reactor (MBfR) using methane as the sole electron donor and carbon source. This work explores how the biofilm's microbial community evolved as the biofilm stage wise reduced different combinations of perchlorate, nitrate, and nitrite. The initial inoculum, carrying out anaerobic methane oxidation coupled to denitrification (ANMO-D), was dominated by uncultured Anaerolineaceae and Ferruginibacter sp. The microbial community significantly changed after it was inoculated into the CH4-based MBfR and fed with a medium containing perchlorate and nitrite. Archaea were lost within the first 40 days, and the uncultured Anaerolineaceae and Ferruginibacter sp. also had significant losses. Replacing them were anoxic methanotrophs, especially Methylocystis, which accounted for more than 25 % of total bacteria. Once the methanotrophs became important, methanol-oxidizing denitrifying bacteria, namely, Methloversatilis and Methylophilus, became important in the biofilm, probably by utilizing organic matter generated by the metabolism of methanotrophs. When methane consumption was equal to the maximum-possible electron-donor supply, Methylomonas, also an anoxic methanotroph, accounted for >10 % of total bacteria and remained a major part of the community until the end of the experiments. We propose that aerobic methane oxidation coupled to denitrification and perchlorate reduction (AMO-D and AMO-PR) directly oxidized methane and reduced NO3 (-) to NO2 (-) or N2O under anoxic condition, producing organic matter for methanol-assimilating denitrification and perchlorate reduction (MA-D and MA-PR) to reduce NO3 (-). Simultaneously, bacteria capable of anaerobic methane oxidation coupled to denitrification and perchlorate reduction (ANMO-D and ANMO-PR) used methane as the electron donor to respire NO3 (-) or ClO4 (-) directly. Graphical Abstract ?. PMID- 26841779 TI - Grey Tienshan Urumqi Glacier No.1 and light-absorbing impurities. AB - The Tienshan Urumqi Glacier No.1 (TUG1) usually shows "grey" surfaces in summers. Besides known regional warming, what should be responsible for largely reducing its surface albedo and making it look "grey"? A field campaign was conducted on the TUG1 on a selected cloud-free day of 2013 after a snow fall at night. Fresh and aged snow samples were collected in the field, and snow densities, grain sizes, and spectral reflectances were measured. Light-absorbing impurities (LAIs) including black carbon (BC) and dust, and number concentrations and sizes of the insoluble particles (IPs) in the samples were measured in the laboratory. High temperatures in summer probably enhanced the snow ageing. During the snow ageing process, the snow density varied from 243 to 458 kg m(-3), associated with the snow grain size varying from 290 to 2500 MUm. The concentrations of LAIs in aged snow were significantly higher than those in fresh snow. Dust and BC varied from 16 ppm and 25 ppb in fresh snow to 1507 ppm and 1738 ppb in aged snow, respectively. Large albedo difference between the fresh and aged snow suggests a consequent forcing of 180 W m(-2). Simulations under scenarios show that snow ageing, BC, and dust were responsible for 44, 25, and 7 % of the albedo reduction in the accumulation zone, respectively. PMID- 26841778 TI - Optimization of operation conditions for the mitigation of nitrous oxide (N2O) emissions from aerobic nitrifying granular sludge system. AB - The optimization of operation parameters is a key consideration to minimize nitrous oxide (N2O) emissions in biological nitrogen removal processes. So far, different parameters have only been investigated individually, making it difficult to compare their specific effects and combined influences. In this study, we applied the Plackett-Burman (PB) multifactorial experimental design and response surface methodology (RSM) analysis to find the optimized condition for the mitigation of N2O release in a nitrifying granular sludge system. Seven parameters (temperature, pH, feeding strategy, C/N ratio, aeration rate, Cu(2+) concentration, and aeration mode) were tested in parallel. Five of them (other than chemical oxygen demand/nitrogen (C/N) ratio and Cu(2+) concentration) were selected as influential factors. Since the type of feeding strategies and aeration modes cannot be quantified, continuous feed strategy and anoxic/oxic aeration mode were applied for the following study. Influences of temperature, pH, and aeration rate on N2O emissions were tested with RSM analysis to further investigate the mutual interactions among the parameters and to identify the optimal values that would minimize N2O release. Results showed the minimum emission value could be obtained under the temperature of 22.3 degrees C, pH of 7.1 and aeration rate of 0.20 m(3)/h. Predicted results were then verified by subsequent validation experiments. The estimated N2O emission value of each design by RSM was also observed in good relationships with experimental result. PMID- 26841780 TI - Residues of plant protection products in grey partridge eggs in French cereal ecosystems. AB - The contamination of the eggs of farmland birds by currently used plant protection products (PPPs) is poorly documented despite a potential to adversely impact their breeding performance. In this context, 139 eggs of 52 grey partridge Perdix perdix clutches, collected on 12 intensively cultivated farmlands in France in 2010-2011, were analysed. Given the great diversity of PPPs applied on agricultural fields, we used exploratory GC/MS-MS and LC/MS-MS screenings measuring ca. 500 compounds. The limit of quantification was 0.01 mg/kg, a statutory reference. A total of 15 different compounds were detected in 24 clutches. Nine of them have been used by farmers to protect crops against fungi (difenoconazole, tebuconazole, cyproconazole, fenpropidin and prochloraz), insects (lambda-cyhalothrin and thiamethoxam/clothianidin) and weeds (bromoxynil and diflufenican). Some old PPPs were also detected (fipronil(+sulfone), HCH(alpha,beta,delta isomers), diphenylamine, heptachlor(+epoxyde), DDT(Sigmaisomers)), as well as PCBs(153, 180). Concentrations ranged between <0.01 and 0.05 mg/kg but reached 0.067 (thiamethoxam/clothianidin), 0.11 (heptachlor + epoxyde) and 0.34 (fenpropidin) mg/kg in some cases. These results testify an actual exposure of females and/or their eggs to PPPs in operational conditions, as well as to organochlorine pollutants or their residues, banned in France since several years if not several decades, that persistently contaminate the environment.Routes of exposure, probability to detect a contamination in the eggs, and effects on egg/embryo characteristics are discussed with regard to the scientific literature. PMID- 26841781 TI - Cat serum contamination by phthalates, PCBs, and PBDEs versus food and indoor air. AB - A wide variety of endocrine disrupting compounds (EDCs) with semi-volatile properties are emitted to indoor air and, thus, humans might get exposed to these compounds. Pet cats spend the major part of their lifetime at home and might integrate indoor contamination so that they could mirror the human exposure. Three classes of EDCs, polybromodiphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and phthalates (PAEs), were simultaneously considered and quantified in the serum of cats (Felis silvestris catus) living in the Paris area (France). The main compound concentrations by decreasing importance order were as follows: for PAEs, di-n-butyl phthalate (79,900 ng L(-1)) next di-iso-butyl phthalate (53,200 ng L(-1)), di-iso-nonyl phthalate (43,800 ng L(-1)), and di ethylhexyl phthalate (32,830 ng L(-1)); for PCBs, CB153 (1378 ng L(-1)) next CB52 (509 ng L(-1)), CB101 (355 ng L(-1)), CB110 (264 ng L(-1)), and CB118 (165 ng L( 1)); and for PBDEs, BDE 153/154 (35 ng L(-1)) next BDE47 (10.7 ng L(-1)). Total serum concentrations as mean +/- standard deviation were 107 +/- 98 MUg L(-1) for ?9PAEs, 2799 +/- 944 ng L(-1) for ?19PCBs, and 56 +/- 21 ng L(-1) for ?9BDEs. The three chemical groups were found in cat food: 0.088 ng g(-1) for ?9BDEs, 1.7 ng g(-1) for ?19PCBs, and 2292 ng g(-1) for ?9PAEs and in indoor air: 0.063 ng m(-3) for ?9BDEs, 1.5 ng m(-3) for ?19PCBs, and 848 ng m(-3) for ?9PAEs. Contaminant intake by food ingestion was approximately 100-fold higher than that by indoor air inhalation. PMID- 26841782 TI - Continuity of care by a primary midwife (caseload midwifery) increases women's satisfaction with antenatal, intrapartum and postpartum care: results from the COSMOS randomised controlled trial. AB - BACKGROUND: Continuity of care by a primary midwife during the antenatal, intrapartum and postpartum periods has been recommended in Australia and many hospitals have introduced a caseload midwifery model of care. The aim of this paper is to evaluate the effect of caseload midwifery on women's satisfaction with care across the maternity continuum. METHODS: Pregnant women at low risk of complications, booking for care at a tertiary hospital in Melbourne, Australia, were recruited to a randomised controlled trial between September 2007 and June 2010. Women were randomised to caseload midwifery or standard care. The caseload model included antenatal, intrapartum and postpartum care from a primary midwife with back-up provided by another known midwife when necessary. Women allocated to standard care received midwife-led care with varying levels of continuity, junior obstetric care, or community-based general practitioner care. Data for this paper were collected by background questionnaire prior to randomisation and a follow-up questionnaire sent at two months postpartum. The primary analysis was by intention to treat. A secondary analysis explored the effect of intrapartum continuity of carer on overall satisfaction rating. RESULTS: Two thousand, three hundred fourteen women were randomised: 1,156 to caseload care and 1,158 to standard care. The response rate to the two month survey was 88% in the caseload group and 74% in the standard care group. Compared with standard care, caseload care was associated with higher overall ratings of satisfaction with antenatal care (OR 3.35; 95% CI 2.79, 4.03), intrapartum care (OR 2.14; 95% CI 1.78, 2.57), hospital postpartum care (OR 1.56, 95% CI 1.32, 1.85) and home-based postpartum care (OR 3.19; 95% CI 2.64, 3.85). CONCLUSION: For women at low risk of medical complications, caseload midwifery increases women's satisfaction with antenatal, intrapartum and postpartum care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN012607000073404 (registration complete 23rd January 2007). PMID- 26841783 TI - Innate Immunity and Inflammation in NAFLD/NASH. AB - Inflammation and hepatocyte injury and death are the hallmarks of nonalcoholic steatohepatitis (NASH), the progressive form of nonalcoholic fatty liver disease (NAFLD), which is a currently burgeoning public health problem. Innate immune activation is a key factor in triggering and amplifying hepatic inflammation in NAFLD/NASH. Thus, identification of the underlying mechanisms by which immune cells in the liver recognize cell damage signals or the presence of pathogens or pathogen-derived factors that activate them is relevant from a therapeutic perspective. In this review, we present new insights into the factors promoting the inflammatory response in NASH including sterile cell death processes resulting from lipotoxicity in hepatocytes as well as into the altered gut-liver axis function, which involves translocation of bacterial products into portal circulation as a result of gut leakiness. We further delineate the key immune cell types involved and how they recognize both damage-associated molecular patterns or pathogen-associated molecular patterns through binding of surface expressed pattern recognition receptors, which initiate signaling cascades leading to injury amplification. The relevance of modulating these inflammatory signaling pathways as potential novel therapeutic strategies for the treatment of NASH is summarized. PMID- 26841786 TI - A Round-Up on Cost-Effectiveness of Hypertension Therapy Based on the 2014 Guidelines. AB - Cardiovascular diseases are the leading cause of death in the USA. Moreover, hypertension affects approximately 78 million people in the USA and is a major modifiable risk factor. Therefore, elevated blood pressure is listed as the primary contributory cause of death in 15 % of the 2.4 million deaths in 2009. Nonetheless, 44 % of the hypertensive population in the USA did not have it under control in 2014. Hypertension cost was averaged to be 40-50 billion dollars yearly including medications and services and currently rising. New hypertension guidelines recommend treating individuals between ages 35 and 74 with different stages of hypertension. Furthermore, individuals with existing co-morbidities such as chronic kidney disease and diabetes should have increased medication adherence and different blood pressure goal compared to those without co morbidities. Studies utilizing quality-adjusted life-years (QUALYs) were conducted to asses the cost-effectiveness of treating previously untreated adults with hypertension. On average, treating adults between ages 35 to 74 years could prevent about 50,000 and 13,000 cardiovascular events and deaths, respectively. Overall, treating stage 1 and 2 hypertension adults including emphasis on medication adherence could be effective and cost saving. The purpose of this article is to review different methods and assess cost-effectiveness for hypertension therapy based on the 2014 guidelines. PMID- 26841784 TI - Follow-Up Study on CDX1 and CDX2 mRNA Expression in Noncancerous Gastric Mucosae After Helicobacter pylori Eradication. AB - BACKGROUND: Changes in CDX1/CDX2 in gastric mucosae following Helicobacter pylori eradication have not been clarified yet. AIMS: To evaluate the changes in CDX1/CDX2 expression after H. pylori eradication, in relation to the reversibility of intestinal metaplasia (IM). METHODS: Time course of CDX1/CDX2 expressions was investigated in 176 subjects with various gastroduodenal disorders. Among them, 132 patients were H. pylori positives; H. pylori were eradicated in 107 of them; 13 failed to eradicate; and 12 did not receive H. pylori eradication therapy. Forty-four subjects were H. pylori negatives. Expression levels in CDX1 and CDX2 from noncancerous gastric mucosae of the corpus, as well as the histologic findings of gastric mucosae, were evaluated during the follow-up. RESULTS: Average follow-up duration was 33.7 months (range 2-97 months). Expression levels in both CDX1 and CDX2 mRNAs were correlated with IM grade in the corpus (rho = 0.633 and 0.554, respectively, all P < 0.001). Changes in CDX1/CDX2 mRNA expressions following H. pylori eradication showed only insignificant results; IM grade at the antrum and corpus showed a tendency to decrease after H. pylori eradication without statistical significance (P > 0.05). However, histologic improvement of IM at the corpus was associated with a decrease in CDX2 mRNA expression during the follow-up (linear mixed model, P for slope = 0.015). CONCLUSIONS: In this study, eradication of H. pylori did not show any beneficial effects on aberrant CDX1/CDX2 expressions or IM. Reversibility of IM may be associated with a decrease in CDX2 mRNA expression. PMID- 26841785 TI - Radionuclide Imaging Applications in Cardiomyopathies and Heart Failure. AB - Multiple epidemiological factors including population aging and improved survival after acute coronary syndromes have contributed to a heart failure (HF) prevalence in the USA in epidemic proportions. In the absence of transplantation, HF remains a progressive disease with poor prognosis. The structural and functional abnormalities of the myocardium in HF can be assessed by various radionuclide imaging techniques. Radionuclide imaging may be uniquely suited to address several important clinical questions in HF such as identifying etiology and guiding the selection of patients for coronary revascularization. Newer approaches such as autonomic innervation imaging, phase analysis for synchrony assessment, and other molecular imaging techniques continue to expand the applications of radionuclide imaging in HF. In this manuscript, we review established and evolving applications of radionuclide imaging for the diagnosis, risk stratification, and management of HF. PMID- 26841787 TI - Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin, other traditional NSAIDs, and coxibs. Evidence obtained during the past 10 years has focused attention on the cardiovascular hazard associated with coxibs and some traditional NSAIDs. The large randomized trials of prolonged coxib treatment added importantly to information provided by epidemiological studies that had previously associated regular use of NSAIDs with increased blood pressure and enhanced risk of congestive heart failure, and identified an increased risk of myocardial infarction as a class effect of cyclooxygenase-2 inhibitors. The aim of this article is to review the cardiovascular effects of aspirin, other traditional NSAIDs, and coxibs, to discuss the mechanisms underlying these effects, and to provide a clinical perspective on the cardiovascular hazard associated with their use. PMID- 26841788 TI - Antithrombotic Therapy After Peripheral Vascular Intervention. AB - Cardioprotective medications and risk-factor modification are the hallmarks of treatment for all patients with peripheral artery disease (PAD). If symptoms are life-limiting and/or do not respond to conservative treatment, endovascular or surgical revascularization can be considered especially for patients with critical limb ischemia or acute limb ischemia. The rates of peripheral vascular intervention (PVI) have risen dramatically over the past few decades and much of this care have shifted from inpatient hospital settings to outpatient settings and office-based clinics. While PVI rates have surged and technology advancements have dramatically changed the face of PVI, the data behind optimal antithrombotic therapy following PVI is scant. Currently in the USA, most patients are treated with indefinite aspirin therapy and a variable duration of clopidogrel (or other P2Y12 inhibitor)-typically 1 month, 3 months, or indefinite therapy. More observational analyses and randomized clinical trials evaluating clinically relevant outcomes such as cardiovascular morbidity/mortality and the risk of bleeding are needed to guide the optimal role and duration of antithrombotic therapy post-PVI. PMID- 26841789 TI - Bringing inorganic chemistry to life with inspiration from R. J. P. Williams. AB - Our appreciation of the scholarly ideas and thinking of Bob Williams is illustrated here by a few of the areas in which he inspired us. His journey to bring inorganic chemistry to life began with an early interest in analytical chemistry, rationalising the relative stabilities of metal coordination complexes (The Irving-Williams Series), and elucidating the organometallic redox chemistry of vitamin B12. He (and Vallee) recognised that metal ions are in energised (entatic) states in proteins and enzymes, which themselves are dynamic structures of rods and springs. He played a key role in helping Rosenberg to pave the road toward the clinic for the anticancer drug cisplatin. He believed that evolution is not just dependent on DNA, but also on the metallome. Organisms and the environment are one system: does DNA code directly for all the essential elements of life? PMID- 26841791 TI - Novel antitumor adamantane-azole gold(I) complexes as potential inhibitors of thioredoxin reductase. AB - Gold complexes that could act as antitumor agents have attracted great attention. Heterocyclic compounds and their metal complexes display a broad spectrum of pharmacological properties. The present study reports the preparation and characterization of four novel gold(I) complexes containing tertiary phosphine and new ligands 5-adamantyl-1,3-thiazolidine-2-thione, 3-methyladamantane-1,3,4 oxadiazole-2-thione. Spectroscopic data suggest that gold is coordinated to the exocyclic sulfur atom in all cases, as confirmed by X-ray crystallographic data obtained for complex (1) and supported by quantum-mechanical calculations. The cytotoxicity of the compounds has been evaluated in comparison to cisplatin and auranofin in three different tumor cell lines, colon cancer (CT26WT), metastatic skin melanoma (B16F10), mammary adenocarcinoma (4T1) and kidney normal cell (BHK 21). The gold complexes were more active than their respective free ligands and able to inhibit the thioredoxin reductase (TrxR) enzyme, even in the presence of albumin. Molecular modeling studies were carried out to understand the interaction between the compounds and the TrxR enzyme, considered as a potential target for new compounds in cancer treatment. The docking results show that the adamantane ring is essential to stabilize the ligand-enzyme complex prior the formation of covalent bond with gold center. The structure of the new gold compounds was established on the basis of spectroscopic data, DFT calculations and X-ray diffraction. TrxR inhibition was evaluated and the results correlated with the assays in tumor cells, suggesting the TrxR as possible target for these compounds. PMID- 26841792 TI - Particle-Associated Ambient Benzo[a]pyrene and Levels of Urinary 1-Hydroxypyrene in a Non-occupationally Exposed Population of Adults and Children in Lanzhou, China. AB - Concentrations of benzo[a]pyrene (B[a]P) in ambient air from different areas in Lanzhou city in northwest of China, and its metabolite 1-hydroxypyrene (1-OHP) in the urine of resident children and adults were determined by using gas chromatography/mass spectrometry and high performance liquid chromatography. Results showed that the atmospheric environmental concentration of B[a]P varied significantly from one part of the city to another with levels of 150 ng/m(3) in the industrial area of Xigu and 73.8 ng/m(3) in the agricultural area of Yuzhong. The geometric mean urinary 1-OHP concentration was 0.42 umol/mol-creatinine, with a range of means between 0.067 and 2.05 for the various population sub-groups. The non-occupationally exposed populations' age, gender and area of residence were the major factors that influenced urinary 1-OHP levels. The health risks of B[a]P for adults and children in Xigu and for children in Yuzhong exceeded the acceptable level (1 * 10(-4)) of the US Environmental Protection Agency. PMID- 26841793 TI - Cerebral infarction caused by a heart-breaking needle: a case report. AB - BACKGROUND: In this report, we describe a case of cerebral infarction caused by cardiac foreign body-induced infective endocarditis. We discuss the paradox of the treatment we used and highlight the need for careful examination of patients without histories and complaints of cardiac disease. CASE PRESENTATION: Our patient was a 48-year-old Asian woman who presented with symptoms of cerebral infarction without any characteristic features of infective endocarditis. Appropriate treatment had been delayed, which made her therapy a little bit complicated. The optimal treatment of our patient was apparently surgery. However, the appropriate timing of her operation is still argued among surgeons at our department because of her acute cerebral infarction. CONCLUSIONS: Patients with cardiac foreign bodies need timely surgery, especially patients who display symptoms of nervous system or cardiovascular system imbalance. In this case report, we share our experiences with treating such a patient, which may have some clinical implications in a contradictory situation. To the best of our knowledge, this report is the first of its kind and will broaden understanding of the clinical diagnosis of this type of case. PMID- 26841790 TI - Dynamic features of carboxy cytoglobin distal mutants investigated by molecular dynamics simulations. AB - Cytoglobin (Cgb) is a member of hemoprotein family with roles in NO metabolism, fibrosis, and tumourigenesis. Similar to other hemoproteins, Cgb structure and functions are markedly influenced by distal key residues. The sixth ligand His(81) (E7) is crucial to exogenous ligand binding, heme pocket conformation, and physiological roles of this protein. However, the effects of other key residues on heme pocket and protein biological functions are not well known. In this work, a molecular dynamics (MD) simulation study of two single mutants in CO ligated Cgb (L46FCgbCO and L46VCgbCO) and two double mutants (L46FH81QCgbCO and L46VH81QCgbCO) was conducted to explore the effects of the key distal residues Leu(46)(B10) and His(81)(E7) on Cgb structure and functions. Results indicated that the distal mutation of B10 and E7 affected CgbCO dynamic properties on loop region fluctuation, internal cavity rearrangement, and heme motion. The distal conformation change was reflected by the distal key residues Gln(62) (CD3) and Arg(84)(E10). The hydrogen bond between heme propionates with CD3 or E10 residues were evidently influenced by B10/E7 mutation. Furthermore, heme pocket rearrangement was also observed based on the distal pocket volume and occurrence rate of inner cavities. The mutual effects of B10 and E7 residues on protein conformational rearrangement and other dynamic features were expressed in current MD studies of CgbCO and its distal mutants, suggesting their crucial role in heme pocket stabilization, ligand binding, and Cgb biological functions. The mutation of distal B10 and E7 residues affects the dynamic features of carboxy cytoglobin. PMID- 26841794 TI - ADAMTS-18 in the host tissues exerts little effect on breast tumor progress in a murine 4T1 breast cancer model. AB - BACKGROUND: In this study, we aimed to identify a novel extracellular proteinase ADAMTS-18 that could be a potential tumor suppressor gene. RESULTS: We successfully constructed Adamts-18 knockout mice with BALB / c background. RT-PCR analysis showed syngeneic mammary tumor cell line 4 T1 per se has weakly endogenous ADAMTS-18 expression. Orthotopic inoculation of 4 T1 cells within the mammary fat pad of host mice, we found no significant difference in tumor growth and metastasis between Adamts-18 knockout mice and widetype control. CONCLUSIONS: We did not confirm that ADAMTS-18 in the host tissues is relevant for breast tumor progress in a murine 4 T1 breast cancer model. PMID- 26841795 TI - Physical activity: The importance of the extended theory of planned behavior, in type 2 diabetes patients. AB - This study focused on the contribution of the extended theory of planned behavior regarding intention to perform physical activity, adherence to physical activity, and its mediator role in the relationship between trust in the physician and adherence to physical activity, in a sample of 120 patients with type 2 diabetes. The results revealed that positive attitudes and perception of control predicted a stronger intention to do physical activity. The intention to do physical activity was the only predictor of adherence to physical activity. Planning mediated the relationship between trust in the physician and adherence. Implications for patients with type 2 diabetes are discussed. PMID- 26841798 TI - Discounting financial costs and health benefits in public health programmes. PMID- 26841797 TI - Annual Cycles of Two Cyanobacterial Mat Communities in Hydro-Terrestrial Habitats of the High Arctic. AB - Cyanobacteria form extensive macroscopic mats in shallow freshwater environments in the High Arctic and Antarctic. In these habitats, the communities are exposed to seasonal freezing and desiccation as well as to freeze-thawing and drying rewetting cycles. Here, we characterized the annual cycles of two Phormidium communities in very shallow seepages located in central Svalbard. We observed the structure of the communities and the morphology, ultrastructure, metabolic activity, and viability of filaments and single cells. The communities overwintered as frozen mats, which were formed by long filaments enclosed in thick multilayered polysaccharide sheaths. No morphologically and/or ultrastructurally distinct spore-like cells were produced for surviving the winter, and the winter survival of the communities was not provided by a few resistant cells, which did not undergo visible morphological and ultrastructural transformations. Instead, a high proportion of cells in samples (85%) remained viable after prolonged freezing. The sheaths were the only morphological adaption, which seemed to protect the trichomes from damage due to freezing and freeze-associated dehydration. The cells in the overwintering communities were not dormant, as all viable cells rapidly resumed respiration after thawing, and their nucleoids were not condensed. During the whole vegetative season, defined by the presence of water in a liquid state, the communities were constantly metabolically active and contained <1% of dead and injured cells. The morphology and ultrastructure of the cells remained unaltered during observations throughout the year, except for light-induced changes in thylakoids. The dissemination events are likely to occur in spring as most of the trichomes were split into short fragments (hormogonia), a substantial proportion of which were released into the environment by gliding out of their sheaths, as well as by cracking and dissolving their sheaths. The short fragments subsequently grew longer and gradually produced new polysaccharide sheaths. PMID- 26841796 TI - Hotspots of boundary accumulation: dynamics and statistics of micro-swimmers in flowing films. AB - Biological flows over surfaces and interfaces can result in accumulation hotspots or depleted voids of microorganisms in natural environments. Apprehending the mechanisms that lead to such distributions is essential for understanding biofilm initiation. Using a systematic framework, we resolve the dynamics and statistics of swimming microbes within flowing films, considering the impact of confinement through steric and hydrodynamic interactions, flow and motility, along with Brownian and run-tumble fluctuations. Micro-swimmers can be peeled off the solid wall above a critical flow strength. However, the interplay of flow and fluctuations causes organisms to migrate back towards the wall above a secondary critical value. Hence, faster flows may not always be the most efficacious strategy to discourage biofilm initiation. Moreover, we find run-tumble dynamics commonly used by flagellated microbes to be an intrinsically more successful strategy to escape from boundaries than equivalent levels of enhanced Brownian noise in ciliated organisms. PMID- 26841799 TI - Community occupational therapy for people with dementia and family carers (COTiD UK) versus treatment as usual (Valuing Active Life in Dementia [VALID] programme): study protocol for a randomised controlled trial. AB - BACKGROUND: A community-based occupational therapy intervention for people with mild to moderate dementia and their family carers (Community Occupational Therapy in Dementia (COTiD)) was found clinically and cost effective in the Netherlands but not in Germany. This highlights the need to adapt and implement complex interventions to specific national contexts. The current trial aims to evaluate the United Kingdom-adapted occupational therapy intervention for people with mild to moderate dementia and their family carers living in the community (COTiD-UK) compared with treatment as usual. METHODS/DESIGN: This study is a multi-centre, parallel-group, pragmatic randomised trial with internal pilot. We aim to allocate 480 pairs, with each pair comprising a person with mild to moderate dementia and a family carer, who provides at least 4 hours of practical support per week, at random between COTiD-UK and treatment as usual. We shall assess participants at baseline, 12 and 26 weeks, and by telephone at 52 and 78 weeks (first 40% of recruits only) after randomisation. The primary outcome measure is the Bristol Activities of Daily Living Scale (BADLS) at 26 weeks. Secondary outcome measures will include quality of life, mood, and resource use. To assess intervention delivery, and client experience, we shall collect qualitative data via audio recordings of COTiD-UK sessions and conduct semi-structured interviews with pairs and occupational therapists. DISCUSSION: COTiD-UK is an evidence-based person-centred intervention that reflects the current priority to enable people with dementia to remain in their own homes by improving their capabilities whilst reducing carer burden. If COTiD-UK is clinically and cost effective, this has major implications for the future delivery of dementia services across the UK. TRIAL REGISTRATION: Current Controlled Trials ISRCTN10748953 Date of registration: 18 September 2014. PMID- 26841801 TI - The transition of renal histopathology after immunosuppressive therapy in a woman with renal limited ANCA-associated vasculitis: a case report and literature review. AB - OBJECTIVES: The kidneys are frequently involved in antineutrophil cytoplasmic autoantibody (ANCA) associated small-vessel vasculitis (AASVV). The pathological hallmark of ANCA-associated glomerulonephritis (AAGN) is a pauci-immune necrotising crescentic glomerulonephritis. The histopathology of AAGN may change during the course of the disease as a consequence of immunosuppressive therapy. Herein, we report the pathological evolution of a case of AAGN. METHODS: We report a female presented with renal-limited AASVV, hypocomplementemia and nephrotic syndrome. The first renal biopsy revealed "crescentic" changes at presentation, but after treatment with immunosuppressive treatment, a second renal biopsy four years later showed "mixed" changes of AAGN and immune complex deposition mimicking a mesangial proliferative glomerulonephritis. A literature review was undertaken in order to understand these transformations and factors which determine the pathological transitions. RESULTS: AAGN is commonly described as a pauci-immune necrotising crescentic glomerulonephritis, but immune complex depositions have been frequently identified under electronic microscopy and is associated with greater levels of proteinuria. Acute lesions such as fibrinoid necrosis or glomerular crescent may completely disappear or reduce significantly after immunosuppressive therapy, but chronic changes may increase over time. CONCLUSIONS: Based on our review and the illustration of this case, the initial histopathology of an AAGN and its active fibrinoid necrosis and cellular glomerular crescent may disappear or resolve after immunosuppressive therapy with resulting non-distinctive feature. Understanding the transition may facilitate the clinical diagnosis and provide further insight into this disease. PMID- 26841802 TI - Should IGHV status and FISH testing be performed in all CLL patients at diagnosis? A systematic review and meta-analysis. AB - Since the first description of the natural history of chronic lymphocytic leukemia (CLL) by David Galton in 1966, the considerable heterogeneity in the disease course has been well recognized. The Rai and Binet staging systems described ~40 years ago have proven to be robust prognostic tools. Over the past 2 decades, several novel biological, genetic, and molecular markers have been shown to be useful adjuncts to the Rai and Binet staging systems. In this systematic review, we examined the role of immunoglobulin heavy-chain variable region gene (IGHV) mutation status and genetic abnormalities determined by interphase fluorescence in situ hybridization (FISH) in patients with newly diagnosed CLL. The cumulative evidence presented in this systematic review is sufficient to recommend that FISH and IGHV be performed as standard clinical tests for all patients with newly diagnosed CLL in those countries with the resources to do so. In addition to clinical stage, these parameters could represent the minimal standard initial prognostic evaluation for patients with CLL. This approach will allow the application of powerful, recently developed prognostic indices (all of which are dependent on IGHV and FISH results) to all patients with newly diagnosed CLL. PMID- 26841804 TI - Levels of Indoxyl Sulfate in Kidney Transplant Patients, and the Relationship With Hard Outcomes. AB - BACKGROUND: Indoxyl sulfate (IS) is a protein-bound uremic toxin that is known to be associated with the risk of cardiovascular (CV) disease and death in both predialysis and dialysis patients. Data on levels of protein-bound uremic toxins in kidney transplant patients are scarce. The study's objective was to evaluate the levels of IS in kidney transplant patients and the relationship with hard outcomes. METHODS AND RESULTS: In 311 kidney transplant patients, IS levels were measured immediately before transplantation (T0), and 1 month (M1) and 12 months (M12) afterwards. Over a mean+/-standard deviation follow-up period of 113+/-29 months, a total of 55 deaths, 70 CV events and 71 graft losses were recorded. We observed a rapid significant decrease (below or near the normal value) in IS levels after kidney transplantation. Total and free IS levels at M12 were significantly higher in non-transplant patients than in transplant patients (P=0.003 and <0.0001 respectively), despite having similar estimated glomerular filtration rates. Lastly, IS levels were not associated with overall mortality, CV events or graft loss at T0, M1 or M12. CONCLUSIONS: IS levels were significantly lower in kidney transplant receipts than in non-recipients suggesting that kidney transplantation protects against an increase in IS levels. IS levels were not associated with hard outcomes in kidney transplant patients. (Circ J 2016; 80: 722-730). PMID- 26841803 TI - Energy vessel sealing systems versus mechanical ligature of the inferior mesenteric artery in laparoscopic sigmoidectomy. AB - PURPOSE: With the development of new devices, our ligation technique of the inferior mesenteric artery changed from mechanical ligature (ML) to energized vessel sealing systems (EVSS) ligature. The aim of this study was to determine if EVSS could be considered as safe and effective as the more convention ML of the inferior mesenteric vessels division during elective laparoscopic left colectomy. METHODS: Between 2001 and 2014, 200 consecutive patients (111 males) of mean age 54.1 years were operated laparoscopically for a symptomatic sigmoid diverticulitis. Vascular interruptions were performed using mechanical ligatures including double clipping, staples or surgical thread (100 patients) or, starting from 2006, with EVSS thereafter (100 patients). Section of the inferior mesenteric artery is performed systematically at its origin in our institution for teaching purposes. Technical results were prospectively collected perioperatively and postoperatively. RESULTS: There was no mortality. Mean operating time was 253.7 and 200.7 min in the ML and EVSS groups, respectively (p < 0.001). Mean hospital stay was 10.4 and 8.1 days (p < 0.001). Thirty-day complications occurred in 31 versus 25 % of patients (p = 0.26). Leakage with peritonitis occurred in 3 patients in the ML group. Hemorrhagic events occurred in both groups (2 in ML group versus 1 in EVSS group). Limitations of the study are its retrospective design and the bias due to the comparison of two historical cohorts. CONCLUSIONS: EVSS for the inferior mesenteric artery are as safe and effective as ML in elective sigmoidectomy for diverticular disease with lower operative time and hospital stay. PMID- 26841805 TI - Baseline Characterization of Japanese Peripheral Arterial Disease Patients - Analysis of Surveillance of Cardiovascular Events in Antiplatelet-Treated Arteriosclerosis Obliterans Patients in Japan (SEASON). AB - BACKGROUND: Despite mounting evidence of increased cardiovascular events in patients with peripheral arterial disease (PAD), the overall incidence of cardiovascular events in PAD patients has not been fully clarified in Japan. The prospective Surveillance of cardiovascular Events in Antiplatelet-treated arterioSclerosis Obliterans patients in JapaN (SEASON) is a prospective observational multicenter study and here we report the baseline clinical characteristics, including atherosclerosis risk factor prevalence, in PAD patients treated with antiplatelet agents. METHODS AND RESULTS: The SEASON registry enrolled 11,375 patients in 1,745 institutions and the data for 10,322 patients were analyzed. At baseline, the average age was 73.8+/-9.9 years, 60.0% were male and 83.9% were in Fontaine stage I or II. They had arteriosclerosis risk factors, such as current smoking (16.2%), hypertension (61.5%), diabetes mellitus (38.3%) and dyslipidemia (38.8%). There were complications including heart disease (29.7%), cerebrovascular disease (17.1%) and chronic kidney disease (14.3%). A subpopulation analysis revealed that the proportions of patients with risk factors were high in patients with lower ankle-brachial pressure index value. CONCLUSIONS: The baseline characteristics of the SEASON population demonstrate that real-world PAD patients have cardiovascular risk factors and comorbidities next to definite PAD patients. Further analysis of this database will contribute to understanding the real-world situation of PAD patients receiving antiplatelet therapy in Japan. (Circ J 2016; 80: 712-721). PMID- 26841806 TI - Coronary Angioscopy for the Evaluation of Vessel Response After Drug-Eluting Stent Implantation. PMID- 26841807 TI - Circulation Journal Awards for the Year 2015. PMID- 26841809 TI - From Knowing Nothing to Knowing What, How and Now: Parents' Experiences of Caring for their Children With Congenital Adrenal Hyperplasia. AB - Objective: This study investigates various kinds of knowing that European parents use when caring for their children with congenital adrenal hyperplasia (CAH). Methods: Semi-structured qualitative interviews with 20 parents of 22 children with CAH. Results: Parents emphasized the importance of knowing what CAH is and what support their child needs, but also knowing how to cope and make sense of the new situation, how to attend to their child's medical needs as well as how to talk to their child. Parents also reported challenges related to connecting with their social network, experiences of emergency care, and how to help their children become independent. These challenges require knowing now : being able to respond appropriately to unique circumstances. Conclusions: Parents experience diverse challenges that may moderate the effects of the diagnosis on children's well-being. Parenting children with CAH requires the development of knowing that goes beyond medical information. PMID- 26841810 TI - Do patients with brain metastases selected for whole brain radiotherapy have worse baseline quality of life as compared to those for radiosurgery or neurosurgery (with or without whole brain radiotherapy)? AB - BACKGROUND: The purpose was to examine the baseline characteristics, symptoms and quality of life (QOL) in patients who receive different treatments for brain metastases. METHODS: Eligible patients were divided and analysed based on their treatment: whole brain radiotherapy (WBRT) alone versus stereotactic radiosurgery (SRS) or neurosurgery with or without WBRT. The Functional Assessment of Cancer Therapy-Brain (FACT-Br) items were grouped according to different domains for summary scores. The domains used for summary scores were physical, social/family, emotional, functional well-being (FWB) and additional concerns. RESULTS: A total of 120 patients were enrolled, with 37 treated with WBRT alone and 83 with SRS or neurosurgery with or without WBRT. Of the 50 baseline FACT-Br items, only five items (I feel ill; I get support from my friends; I worry about dying; I have difficulty expressing my thoughts, I am able to put my thoughts into action) were statistically worse in patients treated with WBRT alone (P<0.05). Patients who received SRS or surgery with or without WBRT had statistically (P<0.05) higher scores for the FWB domain, additional concerns domain, and FACT-G total scores, indicating better QOL. CONCLUSIONS: Patients selected for WBRT alone reported statistically different baseline QOL as compared to patients who were treated with SRS or neurosurgery (with or without WBRT). PMID- 26841808 TI - Overexpression of Tbx20 in Adult Cardiomyocytes Promotes Proliferation and Improves Cardiac Function After Myocardial Infarction. AB - BACKGROUND: Adult mammalian cardiomyocytes (CMs) have the potential to proliferate, but this is not sufficient to generate adequate CMs after myocardial infarction (MI). The transcription factor Tbx20 is required for CM proliferation during development and adult CM homeostasis. The ability of Tbx20 overexpression (Tbx20(OE)) to promote adult CM proliferation and to improve cardiac function after MI was examined. METHODS AND RESULTS: Tbx20(OE) was induced specifically in adult mouse differentiated CMs. Increased CM proliferation and fetal-like characteristics were found in Tbx20(OE) hearts compared with controls without causing pathology 4 weeks after Tbx20(OE) at baseline. Moreover, Tbx20(OE) in adult CM after MI significantly improved survival, cardiac function, and infarct size 4 weeks after MI. Improved cardiac repair, as indicated by increased CM proliferation and capillary density, was observed in the MI border zone of Tbx20(OE) hearts compared with controls. Expression of proliferation activator (cyclin D1, E1, and IGF1) and fetal contractile protein (ssTNI, betaMHC) mRNA was increased whereas negative cell-cycle regulators (p21, Meis1) were decreased in Tbx20(OE) hearts compared with controls under both baseline and MI conditions. Tbx20(OE) in adult hearts activates multiple proproliferation pathways, including Akt, YAP and BMP. Interestingly, p21, Meis1, and a novel cell-cycle inhibitory gene, Btg2, are directly bound and repressed by Tbx20 with induction of proliferation in neonatal CM. CONCLUSIONS: Tbx20(OE), specifically in adult CM, activates multiple cardiac proliferative pathways, directly represses cell-cycle inhibitory genes p21, Meis1, and Btg2, promotes adult CM proliferation; and preserves cardiac performance after MI. PMID- 26841811 TI - Comparison of the EORTC STO-22 and the FACT-Ga quality of life questionnaires for patients with gastric cancer. AB - This review compares the development, characteristics, validity, and reliability of two well-known quality of life (QOL) assessment tools used in patients with gastric cancer: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Stomach (EORTC QLQ-STO22) and the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga). A literature search was conducted using MEDLINE, EMBASE, and Cochrane CENTRAL (inception to April 2015) to identify studies that discussed the development, characteristics, validity and reliability of the EORTC QLQ-STO22 or the FACT-Ga. The QLQ-STO22 was developed with collaboration with patients, healthcare professionals and literature review and was mainly field tested in European countries. Conversely, items on the FACT-Ga were generated from interviews with patients and healthcare professionals concurrently in North America and Asia. While both modules involve a 7-day recall period and use Likert scales, the QLQ-STO22 and FACT-Ga differ in terms of QOL domain focus, quantity and presentation of items, response options, and scoring. However, both tools show good internal consistency, test-retest reliability, sensitivity to change and construct validity. In addition, both questionnaires have been internationally validated within a large sample of patients undergoing a variety of treatments, thus demonstrating their cross-cultural applicability. The EORTC QLQ-STO22 and FACT-Ga are both valid and reliable tools with unique strengths and weaknesses. Selection between instruments should consider specific patient characteristics and goals of the study. PMID- 26841812 TI - The accuracy of clinicians' predictions of survival in advanced cancer: a review. AB - The process of formulating an accurate survival prediction is often difficult but important, as it influences the decisions of clinicians, patients, and their families. The current article aims to review the accuracy of clinicians' predictions of survival (CPS) in advanced cancer patients. A literature search of Cochrane CENTRAL, EMBASE, and MEDLINE was conducted to identify studies that reported clinicians' prediction of survival in advanced cancer patients. Studies were included if the subjects consisted of advanced cancer patients and the data reported on the ability of clinicians to predict survival, with both estimated and observed survival data present. Studies reporting on the ability of biological and molecular markers to predict survival were excluded. Fifteen studies that met the inclusion and exclusion criteria were identified. Clinicians in five studies underestimated patients' survival (estimated to observed survival ratio between 0.5 and 0.92). In contrast, 12 studies reported clinicians' overestimation of survival (ratio between 1.06 and 6). CPS in advanced cancer patients is often inaccurate and overestimated. Given these findings, clinicians should be aware of their tendency to be overoptimistic. Further investigation of predictive patient and clinician characteristics is warranted to improve clinicians' ability to predict survival. PMID- 26841813 TI - Enteral and parenteral nutrition in cancer patients: a systematic review and meta analysis. AB - BACKGROUND: In cancer patients, weight loss is an ominous sign suggesting disease progression and shortened survival time. As a result, providing nutrition support for cancer patients has been proposed as a logical approach for improving clinical outcomes. Nutrition support can be given to patients through enteral nutrition (EN) or parenteral nutrition (PN). The purpose of the review was to compare the outcomes of PN and EN in cancer patients. METHODS: A literature search was conducted in Ovid MEDLINE and OLDMEDLINE, Embase Classic and Embase, and Cochrane Central Register of Controlled Trials. Studies were included if over half of the patient population had cancer and reported on any of the following endpoints: the percentage of patients that experienced no infection, nutrition support complications, major complications or mortality. Risk ratios (RR) and 95% confidence intervals (CIs) using Review Manager Version 5.3 were calculated. Primary endpoints were stratified according to type of EN for subgroup analysis, grouping studies into either tube feeding (TF) or standard care (SC). Additionally, another subgroup analysis was conducted comparing studies with protein-energy malnutrition (PEM) patients and studies without PEM patients. RESULTS: The literature search yielded 674 articles of which 36 were included for the meta-analysis. There were no difference in the endpoints between the two study interventions except that PN resulted in more infection when compared with EN (RR =1.09, 95% CI: 1.01-1.18; P=0.03). CONCLUSIONS: Other than increased incidence of infection, PN has not resulted in prolonging the survival, increasing nutrition support complications, or major complications when compared with EN in cancer patients. PMID- 26841814 TI - Enteral versus parenteral nutrition in cancer patients: evidences and controversies. AB - The debate over the use of enteral nutrition (EN) and parenteral nutrition (PN) is an old but evergreen and hot topic. Since many years, studies comparing EN and PN have been a pivotal 'leitmotif' in the published literature on artificial nutrition (AN). Actually, there is a background misunderstanding in this debate; specifically, that EN and PN are competitors in the choice of the route for delivering nutrition support in cancer patients. Conversely, EN and PN have specific indications and contraindications. This review has the purpose to discuss the indications and complications as well as pros and cons of EN and PN in cancer patients, the crucial role of nutrition support in oncology patients during anticancer treatments and throughout the course of disease, and, finally, the role of AN in advanced cancer patients. In summary, we have no evidence-based data able to definitively indicate the optimal method for delivering AN in cancer patients. EN and PN have to be considered equally effective in maintaining or improving nutritional status in cancer patients. Besides, this review strongly supports the recommendation that a baseline nutritional assessment should be carried out by a healthcare professional expert in AN for all cancer patients at the time of diagnosis or anticancer treatment plan, taking the nutritional status, estimated duration of AN, AN-related potential benefits and possible complications into consideration on an individual basis. Moreover, the patient symptoms, performance status, estimated life expectancy, and mainly, will or preferences have to be evaluated and incorporated into the nutrition support plan before the definitive choice of the route for delivering nutrients is decided. Finally, applying a decision-making process tailored to patient needs-regardless of whether receiving or not anticancer treatment-allows to choose reasonably the optimal nutritional support strategy. PMID- 26841815 TI - Latest advances in the management of radiation-induced pain flare, nausea and vomiting. AB - Palliative radiotherapy (RT) is an effective treatment for symptomatic bone metastases. However, pain flare, nausea and vomiting are common adverse effects associated with this treatment. The management of pain flare and radiation induced nausea and vomiting (RINV) are important endpoints in palliative care. Our report documents the incidence, clinical importance, and advances in the management of these two adverse-effects. We recommend that antiemetic prophylaxis be given based on emetic risk category as outlined in the American Society of Clinical Oncology (ASCO) guidelines. Newer antiemetics investigated in the chemotherapy setting should also be studied in the radiation setting. As there are no guidelines for the use of pain flare prophylaxis at present, further research in this area is needed. PMID- 26841816 TI - Stereotactic body radiation therapy for non-spine bone metastases--a review of the literature. AB - BACKGROUND: Stereotactic body radiation therapy (SBRT) has the ability to deliver significantly higher biologically equivalent doses (BED) compared to conventional radiation treatment. The main goal of SBRT is to improve local tumor control while reducing pain. The side effects however may be greater than those of conventional treatment. METHODS: A review of the literature was conducted and articles pertaining to studies of SBRT in non-spine bone metastases were included. Data on outcomes and toxicities were collected in addition to inclusion and exclusion criteria for each study. RESULTS: A total of 14 studies were included in this review. Very rarely were grade 3 and 4 toxicities reported. Endpoints for the studies varied significantly, which made conclusions of overall local control and progression free survival near impossible. In studies that reported local control rates, these rates were all greater than 85%. Progression free survival varied significantly between studies. CONCLUSIONS: Due to the lack of consistency in endpoint definitions, it is difficult to compare outcomes across trials. There is a need for consensus in endpoint definitions. PMID- 26841817 TI - Opioid withdrawal presenting only nausea during tapering of oxycodone after celiac plexus block: a case report. AB - Celiac plexus block (CPB) is an effective treatment for patients suffering pain. CPB may allow for a reduction in opioid dosage, and may alleviate some of the unwanted side effects of these drugs. However, there is a substantial risk of withdrawal symptoms after reduction of opioid dose. We describe a case of pancreatic cancer developing opioid withdrawal after CPB, who presented only nausea. A 70-year-old man was referred to our hospital due to severe pancreatic cancer pain. He was administered oxycodone (oxycontin(r)) at 240 mg per day, and presented nausea and anorexia as side effects. CPB was performed due to insufficient pain relief. His pain disappeared on the same day as treatment. Oxycodone was reduced to 160 mg/day, and further reduced two days later to 80 mg/day. However, he complained of more severe nausea and loss of appetite even after tapering of oxycodone. Physical examination, blood chemistry examination, and brain computed tomography (CT) showed no abnormalities. Administration of fast-release oxycodone (Oxinome(r)) at a dose of 10 mg immediately improved his nausea. There have been no previous reports of nausea as the sole symptom of opioid withdrawal. The present case indicates that unless opioid side effects improve after dosage reduction, the possibility that they may be withdrawal symptoms should also be considered. PMID- 26841800 TI - Psychedelics. AB - Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5 hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics. Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybin-assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level-dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain's default mode network. PMID- 26841818 TI - Is it possible to teach pain therapy playing basketball? PMID- 26841819 TI - Society for palliative radiation oncology: founding, vision, and report from the Second Annual Meeting. PMID- 26841820 TI - Quality of life, predictions of survival, feeding options, and symptom control for patients with advanced disease. PMID- 26841821 TI - Experiences from Auditory Brainstem Implantation (ABIs) in four paediatric patients. AB - INTRODUCTION: Indications for auditory brainstem implants (ABIs) have been widened from patients with neurofibromatosis type 2 (NF2) to paediatric patients with congenital cochlear malformations, cochlear nerve hypoplasia/aplasia, or cochlear ossification after meningitis. We present four ABI surgeries performed in children at Uppsala University Hospital in Sweden since 2009. METHODS: Three children were implanted with implants from Cochlear Ltd. (Lane Cove, Australia) and one child with an implant from MedEl GMBH (Innsbruck, Austria). A boy with Goldenhar syndrome was implanted with a Cochlear Nucleus ABI24M at age 2 years (patient 1). Another boy with CHARGE syndrome was implanted with a Cochlear Nucleus ABI541 at age 2.5 years (patient 2). Another boy with post-ossification meningitis was implanted with a Cochlear Nucleus ABI24M at age 4 years (patient 3). A girl with cochlear aplasia was implanted with a MedEl Synchrony ABI at age 3 years (patient 4). In patients 1, 2, and 3, the trans-labyrinthine approach was used, and in patient 4 the retro-sigmoid approach was used. RESULTS: Three of the four children benefited from their ABIs and use it full time. Two of the full time users had categories of auditory performance (CAP) score of 4 at their last follow up visit (6 and 2.5 years postoperative) which means they can discriminate consistently any combination of two of Ling's sounds. One child has not been fully evaluated yet, but is a full time user and had CAP 2 (responds to speech sounds) after 3 months of ABI use. No severe side or unpleasant stimulation effects have been observed so far. There was one case of immediate electrode migration and one case of implant device failure after 6.5 years. CONCLUSION: ABI should be considered as an option in the rehabilitation of children with similar diagnoses. PMID- 26841822 TI - Tailor-made ion-imprinted polymer based on functionalized graphene oxide for the preconcentration and determination of trace copper in food samples. AB - A tailor-made Cu(II) ion-imprinted polymer based on large-surface-area graphene oxide sheets has been synthesized for the preconcentration and determination of trace copper from food samples by solid-phase extraction. Attributed to the ultrahigh surface area and hydrophilicity of graphene oxide, the Cu(II) ion imprinted polymer prepared by the surface ion-imprinting technique exhibited a high binding capacity and a fast adsorption rate under the optimized experimental conditions. In the static adsorption experiments, the maximum adsorption capacity of Cu(II) ion-imprinted polymer is 109.38 mg/g at 25 degrees C, which is much higher than that of the nonimprinted polymer (32.12 mg/g). Meanwhile, the adsorption is very rapid and equilibrium is reached after approximately 30 min. The adsorption mechanism is found to follow Langmuir adsorption model and the pseudo-second-order adsorption process. The Cu(II) ion-imprinted polymer was used for extracting and detecting Cu(II) in food samples combined with graphite flame atomic adsorption spectrometry with high recoveries in the range of 97.6-103.3%. The relative standard deviation and limit of detection of the method were evaluated as 1.2% and 0.37 MUg/L, respectively. The results showed that the novel absorbent can be utilized as an effective material for the selective enrichment and determination of Cu(II) from food samples. PMID- 26841823 TI - Na+-sensitive elevation in blood pressure is ENaC independent in diet-induced obesity and insulin resistance. AB - The majority of patients with obesity, insulin resistance, and metabolic syndrome have hypertension, but the mechanisms of hypertension are poorly understood. In these patients, impaired sodium excretion is critical for the genesis of Na(+) sensitive hypertension, and prior studies have proposed a role for the epithelial Na(+) channel (ENaC) in this syndrome. We characterized high fat-fed mice as a model in which to study the contribution of ENaC-mediated Na(+) reabsorption in obesity and insulin resistance. High fat-fed mice demonstrated impaired Na(+) excretion and elevated blood pressure, which was significantly higher on a high Na(+) diet compared with low fat-fed control mice. However, high fat-fed mice had no increase in ENaC activity as measured by Na(+) transport across microperfused cortical collecting ducts, electrolyte excretion, or blood pressure. In addition, we found no difference in endogenous urinary aldosterone excretion between groups on a normal or high-Na(+) diet. High fat-fed mice provide a model of metabolic syndrome, recapitulating obesity, insulin resistance, impaired natriuresis, and a Na(+)-sensitive elevation in blood pressure. Surprisingly, in contrast to previous studies, our data demonstrate that high fat feeding of mice impairs natriuresis and produces elevated blood pressure that is independent of ENaC activity and likely caused by increased Na(+) reabsorption upstream of the aldosterone-sensitive distal nephron. PMID- 26841827 TI - Parkinson's disease: towards better preclinical models and personalized treatments. PMID- 26841824 TI - Resistant starch alters gut microbiome and metabolomic profiles concurrent with amelioration of chronic kidney disease in rats. AB - Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xenometabolites). The fermentable dietary fiber high amylose maize-resistant starch type 2 (HAMRS2) has been shown to alter the gut milieu and in CKD rat models leads to markedly improved kidney function. The aim of the present study was to identify specific cecal bacteria and cecal, blood, and urinary metabolites that associate with changes in kidney function to identify potential mechanisms involved with CKD amelioration in response to dietary resistant starch. Male Sprague-Dawley rats with adenine-induced CKD were fed a semipurified low-fiber diet or a high-fiber diet [59% (wt/wt) HAMRS2] for 3 wk (n = 9 rats/group). The cecal microbiome was characterized, and cecal contents, serum, and urine metabolites were analyzed. HAMRS2-fed rats displayed decreased cecal pH, decreased microbial diversity, and an increased Bacteroidetes-to-Firmicutes ratio. Several uremic retention solutes were altered in the cecal contents, serum, and urine, many of which had strong correlations with specific gut bacteria abundances, i.e., serum and urine indoxyl sulfate were reduced by 36% and 66%, respectively, in HAMRS2-fed rats and urine p-cresol was reduced by 47% in HAMRS2-fed rats. Outcomes from this study were coincident with improvements in kidney function indexes and amelioration of CKD outcomes previously reported for these rats, suggesting an important role for microbial-derived factors and gut microbe metabolism in regulating host kidney function. PMID- 26841828 TI - Reconfigurable liquid-core/liquid-cladding optical waveguides with dielectrophoresis-driven virtual microchannels on an electromicrofluidic platform. AB - An electrically reconfigurable liquid-core/liquid-cladding (L(2)) optical waveguide with core liquid gamma-butyrolactone (GBL, ncore = 1.4341, epsiloncore = 39) and silicone oil (ncladding = 1.401, epsiloncladding = 2.5) as cladding liquid is accomplished using dielectrophoresis (DEP) that attracts and deforms the core liquid with the greater permittivity to occupy the region of strong electric field provided by Teflon-coated ITO electrodes between parallel glass plates. Instead of continuously flowing core and cladding liquids along a physical microchannel, the DEP-formed L(2) optical waveguide guides light in a stationary virtual microchannel that requires liquids of limited volume without constant supply and creates stable liquid/liquid interfaces for efficient light guidance in a simply fabricated microfluidic device. We designed and examined (1) stationary and (2) moving L(2) optical waveguides on the parallel-plate electromicrofluidic platform. In the stationary L-shaped waveguide, light was guided in a GBL virtual microchannel core for a total of 27.85 mm via a 90 degrees bend (radius 5 mm) before exiting from the light outlet of cross sectional area 100 MUm * 100 MUm. For the stationary spiral waveguide, light was guided in a GBL core containing Rhodamine 6G (R6G, 1 mM) and through a series of 90 degrees bends with decreasing radii from 5 mm to 2.5 mm. With the stationary straight waveguide, the propagation loss was measured to be 2.09 dB cm(-1) in GBL with R6G (0.01 mM). The moving L-shaped waveguide was implemented on a versatile electromicrofluidic platform on which electrowetting and DEP were employed to generate a precise GBL droplet and form a waveguide core. On sequentially applying appropriate voltage to one of three parallel L-shaped driving electrodes, the GBL waveguide core was shifted; the guided light was switched at a speed of up to 0.929 mm s(-1) (switching period 70 ms, switching rate 14.3 Hz) when an adequate electric signal (173.1 VRMS, 100 kHz) was applied. PMID- 26841829 TI - Establishment of isogenic iPSCs from an individual with SCN1A mutation mosaicism as a model for investigating neurocognitive impairment in Dravet syndrome. AB - Dravet syndrome (DS) is a severe childhood epilepsy typically caused by de novo dominant mutations in SCN1A. Although patients with DS frequently have neurocognitive abnormalities, the precise neural mechanisms responsible for their expression have not been elucidated. There are wide phenotypic differences among individuals with SCN1A mutations, suggesting that factors other than the SCN1A mutation modify the phenotype. Therefore, a well-controlled cellular model system is required to improve our understanding of the mechanisms underlying DS. Here we generated induced pluripotent stem cell (iPSC) lines from an individual with SCN1A mutation mosaicism, and separately cloned iPSC lines both with and without the SCN1A mutation. These clones theoretically have the same genetic backgrounds, except for the SCN1A gene, and should serve as an ideal pair for investigating the pathophysiology caused by SCN1A mutations. Quantitative reverse transcription PCR and western blot analysis revealed higher tyrosine hydroxylase mRNA and protein expression levels in mutant neurons than in wild-type neurons. Moreover, dopamine concentrations in media collected from mutant neural cultures were higher than those from wild-type neural cultures. Our findings suggest that SCN1A mutation leads to changes in the dopamine system that may contribute to the behavioral abnormalities in DS. PMID- 26841830 TI - New massive parallel sequencing approach improves the genetic characterization of congenital myopathies. AB - Congenital myopathies (CMs) are a heterogeneous group of muscle diseases characterized by hypotonia, delayed motor skills and muscle weakness with onset during the first years of life. The diagnostic workup of CM is highly dependent on the interpretation of the muscle histology, where typical pathognomonic findings are suggestive of a CM but are not necessarily gene specific. Over 20 loci have been linked to these myopathies, including three exceptionally large genes (TTN, NEB and RYR1), which are a challenge for molecular diagnosis. We developed a new approach using massive parallel sequencing (MPS) technology to simultaneously analyze 20 genes linked to CMs. Assay design was based on the Ion AmpliSeq strategy and sequencing runs were performed on an Ion PGM system. A total of 12 patients were analyzed in this study. Among the 2534 variants detected, 14 pathogenic mutations were successfully identified in the DNM2, NEB, RYR1, SEPN1 and TTN genes. Most of these had not been documented and/or fully characterized, hereby contributing to expand the CM mutational spectrum. The utility of this approach was demonstrated by the identification of mutations in 70% of the patients included in this study, which is relevant for CMs especially considering its wide phenotypic and genetic heterogeneity. PMID- 26841831 TI - Charting the Y-chromosome ancestry of present-day Argentinean Mennonites. AB - Old Order Mennonite communities initially arose in Northern Europe (centered in the Netherlands) and derived from the Anabaptist movement of the 16th century. Mennonites migrated to the New World in the early 18th century, first to North America, and more recently to Mesoamerica and South America. We analyzed Y chromosome short tandem repeats (STRs) and single nucleotide polymorphisms in males from a community of Mennonites, 'La Nueva Esperanza', which arrived to Argentina in 1985 from colonies in Bolivia and Mexico. Molecular diversity indices coupled with demographic simulations show that Mennonites have a reduced variability when compared with local Argentinean populations and 69 European population samples. Mennonite Y-STR haplotypes were mainly observed in Central Europe. In agreement, multidimensional scaling analyses based on RST genetic distances indicate that Mennonite Y-chromosomes are closely related to Central/Northern Europeans (the Netherlands, Switzerland and Denmark). In addition, statistical inferences made on the most likely geographic origin of Y chromosome haplotypes point more specifically to the Netherlands as the populations that best represent the majority of the Mennonite Y-chromosomes. Overall, Y-chromosome variation of Mennonites shows the signatures of moderate reduction of variability when compared with source populations, which is in good agreement with their lifestyle in small endogamous demes. These genetic singularities could also help to understand disease conditions that are more prevalent among Mennonites. PMID- 26841832 TI - Decreased B and T lymphocyte attenuator in Behcet's disease may trigger abnormal Th17 and Th1 immune responses. AB - Behcet's disease (BD) is a chronic, systemic and recurrent inflammatory disease associated with hyperactive Th17 and Th1 immune responses. Recent studies have shown that B and T lymphocyte attenuator (BTLA) negatively regulates the immune response. In this study, we investigated whether BTLA activation could be exploited to inhibit the development of abnormal immune responses in BD patients. BTLA expression in PBMCs and CD4(+) T cells was significantly decreased in active BD patients. Decreased BTLA level was associated with increased Th17 and Th1 responses. Activation of BTLA inhibited the abnormal Th17 and Th1 responses and IL-22 expression in both patients and controls. Addition of an agonistic anti BTLA antibody remarkably inhibited DC-induced Th17 and Th1 cell responses, resulted in decreased production of the Th17 and Th1-related cytokines IL-1beta, IL-6, IL-23 and IL-12p70 and reduced CD40 expression in DCs. In conclusion, decreased BTLA expression in ocular BD may lead to inappropriate control of the Th17 and Th1 immune responses and DC functions. Therefore, BTLA may be involved in the development and recurrence of this disease. Agonistic agents of BTLA may represent a potential therapeutic approach for the treatment of BD and other inflammatory diseases mediated by abnormal Th17 and Th1 immune responses. PMID- 26841833 TI - A Dual Target-directed Agent against Interleukin-6 Receptor and Tumor Necrosis Factor alpha ameliorates experimental arthritis. AB - A considerable proportion of patients with rheumatoid arthritis (RA) do not respond to monospecific agents. The purpose of our study was to generate a hybrid form of biologics, targeting tumor-necrosis factor alpha (TNFalpha) and interleukin-6 receptor (IL-6R), and determine its anti-arthritic properties in vitro and in vivo. A novel dual target-directed agent (DTA(A7/sTNFR2)) was generated by conjugating soluble TNF receptor 2 (sTNFR2) to the Fc region of A7, a new anti-IL-6R antibody obtained by screening the phage display human antibody library. DTA(A7/sTNFR2) inhibited the proliferation and migration of fibroblast like synoviocytes from patients with RA (RA-FLS) more efficiently than single target-directed agents. DTA(A7/sTNFR2) also blocked osteoclastogenesis from bone marrow cells. The arthritis severity scores of the experimental arthritis mice with DTA(A7/sTNFR2) tended to be lower than those of mice with IgG, A7, or sTNFR2. Histological data suggested that DTA(A7/sTNFR2) is more efficient than single-target drugs in preventing joint destruction and bone loss. These results were confirmed in vivo using the minicircle system. Taken together, the results show that DTA(A7/sTNFR2) may be a promising therapeutic agent for the treatment of RA. PMID- 26841835 TI - Vitiligo-like depigmentation with perifollicular pigment retention in systemic sclerosis treated successfully with suplatast tosilate. PMID- 26841836 TI - Corrigendum: Organ-wide 3D-imaging and topological analysis of the continuous microvascular network in a murine lymph node. PMID- 26841834 TI - Genome-wide association and high-resolution phenotyping link Oryza sativa panicle traits to numerous trait-specific QTL clusters. AB - Rice panicle architecture is a key target of selection when breeding for yield and grain quality. However, panicle phenotypes are difficult to measure and susceptible to confounding during genetic mapping due to correlation with flowering and subpopulation structure. Here we quantify 49 panicle phenotypes in 242 tropical rice accessions with the imaging platform PANorama. Using flowering as a covariate, we conduct a genome-wide association study (GWAS), detect numerous subpopulation-specific associations, and dissect multi-trait peaks using panicle phenotype covariates. Ten candidate genes in pathways known to regulate plant architecture fall under GWAS peaks, half of which overlap with quantitative trait loci identified in an experimental population. This is the first study to assess inflorescence phenotypes of field-grown material using a high-resolution phenotyping platform. Herein, we establish a panicle morphocline for domesticated rice, propose a genetic model underlying complex panicle traits, and demonstrate subtle links between panicle size and yield performance. PMID- 26841837 TI - Structural basis of complement membrane attack complex formation. AB - In response to complement activation, the membrane attack complex (MAC) assembles from fluid-phase proteins to form pores in lipid bilayers. MAC directly lyses pathogens by a 'multi-hit' mechanism; however, sublytic MAC pores on host cells activate signalling pathways. Previous studies have described the structures of individual MAC components and subcomplexes; however, the molecular details of its assembly and mechanism of action remain unresolved. Here we report the electron cryo-microscopy structure of human MAC at subnanometre resolution. Structural analyses define the stoichiometry of the complete pore and identify a network of interaction interfaces that determine its assembly mechanism. MAC adopts a 'split washer' configuration, in contrast to the predicted closed ring observed for perforin and cholesterol-dependent cytolysins. Assembly precursors partially penetrate the lipid bilayer, resulting in an irregular beta-barrel pore. Our results demonstrate how differences in symmetric and asymmetric components of the MAC underpin a molecular basis for pore formation and suggest a mechanism of action that extends beyond membrane penetration. PMID- 26841839 TI - Microbial communities play important roles in modulating paddy soil fertility. AB - We studied microbial communities in two paddy soils, which did not receive nitrogen fertilization and were distinguished by the soil properties. The two microbial communities differed in the relative abundance of gram-negative bacteria and total microbial biomass. Variability in microbial communities between the two fields was related to the levels of phosphorus and soil moisture. Redundancy analysis for individual soils showed that the bacterial community dynamics in the high-yield soil were significantly correlated with total carbon, moisture, available potassium, and pH, and those in the low-yield cores were shaped by pH, and nitrogen factors. Biolog Eco-plate data showed a more active microbial community in the high yield soil. The variations of enzymatic activities in the two soils were significantly explained by total nitrogen, total potassium, and moisture. The enzymatic variability in the low-yield soil was significantly explained by potassium, available nitrogen, pH, and total carbon, and that in the high-yield soil was partially explained by potassium and moisture. We found the relative abundances of Gram-negative bacteria and Actinomycetes partially explained the spatial and temporal variations of soil enzymatic activities, respectively. The high-yield soil microbes are probably more active to modulate soil fertility for rice production. PMID- 26841840 TI - [Maria Bandeira: a pioneering botanist at the Botanic Garden of Rio de Janeiro]. AB - This article sheds light on Maria Bandeira, the first female botanist to work at the Botanic Garden of Rio de Janeiro. She was active in the 1920s, but is absent from the historiography and little cited in the scientific literature. The significant number of plant, fungus, and lichen specimens she collected, her capacity to reach far-flung places, her extensive correspondence with foreign experts, and her studies at Sorbonne are all sources for the analysis of the way botany was practiced and the social networks at play in science at the time. The end of her scientific career, when she adopted a cloistered life with the Barefoot Carmelite nuns, can be interpreted variously, and partially explains why her contributions to Brazilian botany have been forgotten. PMID- 26841842 TI - [An enigma named Agostino Gemelli: Catholicism, fascism and psychoanalysis in Italy during the inter-war period]. AB - The Franciscan friar Agostino Gemelli has been the subject of much research and debate. This is due to his important political profile and, above all, to the role he played in mediating between the Catholic world and fascism in Italy during the inter-war period. Gemelli was also a central figure in Italian psychology, especially during the 1930s and 1940s. This article is structured to focus in particular on the way that his connections with political and ecclesiastic powers allowed him to become increasingly significant within Italian psychology. Using the example of Gemelli's relationship with psychoanalysis, this study highlights the tension between his relatively open-minded stance and his links to authoritarian, dogmatic ideologies and institutions. PMID- 26841846 TI - [The madman of Itaguai, history, madness, and psychiatric knowledge: historiographic dialogues about "The Alienist," by Machado de Assis]. AB - From the early 1970s until more recently, historiography (which is not always written by historians) has investigated the psychiatric intervention practices that prevailed in Brazil from the latter half of the nineteenth century through the early twentieth, along with their theoretical foundations and the underlying logics of power and sociability. The article analyzes the novella "The Alienist," by Machado de Assis, by engaging in dialogue with this field. The book is interpreted as a robust and eminently critical "historical witness" of the early emergence of mental health medicine in Brazil and its institutional correlate, the asylum. PMID- 26841847 TI - MicroRNA-101 targets von Hippel-Lindau tumor suppressor (VHL) to induce HIF1alpha mediated apoptosis and cell cycle arrest in normoxia condition. AB - The activation/inactivation of HIF1alpha is precisely regulated in an oxygen dependent manner. HIF1alpha is essential for hypoxia induced apoptosis and cell cycle arrest. Several recent studies indicated that the expression of miRNAs can be modulated by hypoxia. However, the involvement of miRNAs in the regulation of HIF1alpha induction remains elusive. In present study, we demonstrated that miR 101 was rapidly and transiently induced after hypoxia in breast cancer cells. Over-expression of miR-101 significantly inhibited cell proliferation in breast cancer cells through increased apoptosis and cell cycle arrest in normoxia condition. This inhibitory phenomenon seems due to miR-101-mediated induction of HIF1alpha, because we identified that VHL, a negative regulator of HIF1alpha, is a novel target of miR-101 and over-expression of miR-101 decreased VHL levels and subsequently stabilized HIF1alpha and induced its downstream target VEGFA. Furthermore, we demonstrated that siRNA-mediated knockdown of VHL or HIF1alpha overexpression could also induce apoptosis and cell cycle arrest whereas enforced expression of VHL, administration of anti-miR-101 oligos or treatment of 2-MeOE2, an inhibitor of HIF1alpha, could rescue cells from such inhibition. These results reveal a novel regulatory mechanism of HIF1alpha induction in normoxia and suggest that miR-101 mediated proliferation inhibition may through HIF1alpha mediated apoptosis and cell cycle arrest. PMID- 26841848 TI - Reverse-migrated neutrophils regulated by JAM-C are involved in acute pancreatitis-associated lung injury. AB - Junctional adhesion molecule-C (JAM-C) plays a key role in the promotion of the reverse transendothelial migration (rTEM) of neutrophils, which contributes to the dissemination of systemic inflammation and to secondary organ damage. During acute pancreatitis (AP), systemic inflammatory responses lead to distant organ damage and typically result in acute lung injury (ALI). Here, we investigated the role of rTEM neutrophils in AP-associated ALI and the molecular mechanisms by which JAM-C regulates neutrophil rTEM in this disorder. In this study, rTEM neutrophils were identified in the peripheral blood both in murine model of AP and human patients with AP, which elevated with increased severity of lung injury. Pancreatic JAM-C was downregulated during murine experimental pancreatitis, whose expression levels were inversely correlated with both increased neutrophil rTEM and severity of lung injury. Knockout of JAM-C resulted in more severe lung injury and systemic inflammation. Significantly greater numbers of rTEM neutrophils were present both in the circulation and pulmonary vascular washout in JAM-C knockout mice with AP. This study demonstrates that during AP, neutrophils that are recruited to the pancreas may migrate back into the circulation and then contribute to ALI. JAM-C downregulation may contribute to AP-associated ALI via promoting neutrophil rTEM. PMID- 26841849 TI - Gerstmann-Straussler-Scheinker disease subtypes efficiently transmit in bank voles as genuine prion diseases. AB - Gerstmann-Straussler-Scheinker disease (GSS) is an inherited neurodegenerative disorder associated with mutations in the prion protein gene and accumulation of misfolded PrP with protease-resistant fragments (PrP(res)) of 6-8 kDa. With the exception of a few GSS cases characterized by co-accumulation of PrP(res) of 21 kDa, efforts to transmit GSS to rodents have been unsuccessful. As a result, GSS subtypes exclusively associated with 6-8 kDa PrP(res) have often been considered as non-transmissible proteinopathies rather than true prion diseases. We show that GSS with P102L, A117V and F198S mutations transmit efficiently and produce distinct pathological phenotypes in bank voles (M. glareolus), irrespective of the presence of 21 kDa PrP(res) in the inoculum, demonstrating that GSS is a genuine prion disease characterized by both transmissibility and strain variation. PMID- 26841850 TI - Histological findings in the spleen affected by adult-onset Still's disease: a report of three cases. PMID- 26841851 TI - Children of Depressed Parents--A Public Health Opportunity. PMID- 26841852 TI - Development and Characterization of Novel LipoCEST Agents Based on Thermosensitive Liposomes. AB - PURPOSE: To develop a novel probe for chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) based on thermosensitive liposomes (lipoCEST) for theranostics, in which diagnostics and therapy are integrated into a single platform. METHODS: We developed two kinds of lipoCEST agents. The first kind encapsulated dysprosium (Dy)-1,4,7,10-tetraazacyclododecane-1,4,7,10 tetraacetic acid (DOTA)-Na.3NaCl, terbium-DOTA-Na.3NaCl, or thulium-DOTA-Na.3NaCl into the inner cavity of thermosensitive liposomes, while the second kind encapsulated Dy-DOTA-Na and incorporated amphiphilic metal complex [thulium diethylenetriamine pentaacetic acid-bis (stearylamide) (Tm-DTPA-BSA)] as a membrane constituent. The nuclear magnetic resonance (NMR)- and Z-spectra of these lipoCEST agents were acquired at various temperatures on a 9.4T MRI scanner. To investigate their applicability to the drug release induced by hyperthermia, we also encapsulated a fluorescent dye (calcein) into the inner cavity of liposomes and measured calcein release after warming them. RESULTS: The intra- and extraliposomal water signals could be differentiated in all agents from their NMR- and Z-spectra. The agent incorporating Tm-DTPA-BSA showed the largest chemical shift (approximately 15 ppm) derived from the intraliposomal water protons. The calcein retained in this agent was successfully released at 44 degrees C. The agent incorporating 30 mol% of Tm-DTPA-BSA in its membrane released more calcein at 42-44oC than that of the agent incorporating 10 mol%. CONCLUSION: We developed novel thermosensitive lipoCEST agents and characterized them. Our preliminary results suggest that they are useful and can be applied to theranostics. PMID- 26841853 TI - Feasibility of Non-contrast-enhanced MR Angiography Using the Time-SLIP Technique for the Assessment of Pulmonary Arteriovenous Malformation. AB - PURPOSE: The purpose of this study was to evaluate the diagnostic performance of non-contrast-enhanced magnetic resonance angiography with time-spatial labeling inversion pulse (time-SLIP MRA) in the assessment of pulmonary arteriovenous malformation (PAVM). METHODS: Eleven consecutive patients with 38 documented PAVMs underwent time-SLIP MRA with a 3-tesla unit. Eight patients with 25 lesions were examined twice, once before and once after embolotherapy. The lesions were divided into two groups-initial diagnosis (n = 35) and follow-up (n = 28) corresponding to untreated and treated lesions, respectively, and were evaluated separately. To evaluate the initial diagnosis group, two reviewers assessed image quality for visualization of PAVMs by using a qualitative 4-point scale (1 = not assessable to 4 = excellent). The location and classification of PAVMs were also evaluated. The results were compared with those from digital subtraction angiography. For evaluation of the follow-up group, the reviewers assessed the status of treated PAVMs. Reperfusion and occlusion were defined respectively as visualization or disappearance of the aneurysmal sac. The diagnostic accuracy of time-SLIP MRA was assessed and compared with standard reference images. Interobserver agreement was evaluated with the kappa statistic. RESULTS: In the initial diagnosis group, time-SLIP MRA correctly determined the PAVMs in all but one patient with one lesion who had image degradation due to irregular breath. Image quality was considered excellent (median = 4) and the kappa coefficient was 0.85. Additionally, both readers could correctly localize and classify the PAVMs on time-SLIP MRA images with both kappa coefficient of 1.00. In the follow-up group, the sensitivity and specificity of time-SLIP MRA for reperfusion of PAVMs were both 100%, and the kappa coefficient was 1.00. CONCLUSION: Time-SLIP MRA is technically and clinically feasible and represents a promising technique for noninvasive pre- and post-treatment assessment of PAVMs. PMID- 26841854 TI - Diffusional Kurtosis Imaging in Idiopathic Normal Pressure Hydrocephalus: Correlation with Severity of Cognitive Impairment. AB - PURPOSE: Diffusional kurtosis imaging (DKI) is an emerging technique that describes diffusion of water molecules in terms of deviation from Gaussian distribution. This study investigated correlations between DKI metrics and cognitive function in patients with idiopathic normal pressure hydrocephalus (iNPH). MATERIALS AND METHODS: DKI was performed in 29 iNPH patients and 14 age matched controls. Mini-mental state examination (MMSE), frontal assessment battery (FAB), and trail making test A (TMT-A) were used as cognitive measures. Tract-based spatial statistics (TBSS) analyses were performed to investigate the between-group differences and correlations with the cognitive measures of the diffusion metrics, including mean kurtosis (MK), fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). RESULTS: In iNPH patients, FA and MK identified positive correlations with cognitive function in similar regions, predominantly in the frontal lobes (P < 0.05, corrected for multiple comparisons). The frontoparietal subcortical white matter showed significant correlations with FAB and TMT-A across more extensive areas in MK analyses than in FA. ADC, AD, and RD analyses showed no significant correlations with MMSE and FAB, while negative correlation with TMT-A was observed in the limited portion of the frontal deep white matter. CONCLUSION: Both FA and MK correlated well with cognitive impairment in iNPH. The observed differences between FA and MK results suggest DKI may play a complementary role to conventional FA and ADC analyses, especially for evaluation of the subcortical white matter. PMID- 26841855 TI - Juxtacortical Lesions in Multiple Sclerosis: Assessment of Gray Matter Involvement Using Phase Difference-enhanced Imaging (PADRE). AB - PURPOSE: In multiple sclerosis (MS), a juxtacortical lesion at the border between the gray matter (GM) and subcortical white matter (WM) may often involve the GM. A recently developed, phase-weighted magnetic resonance imaging (MRI) technique "phase difference enhanced imaging (PADRE)" can delineate the GM and WM clearly due to the difference in myelin concentration. We evaluated whether PADRE is useful for the detection of GM involvement in the juxtacortical MS lesions. METHODS: One neuroradiologist reviewed the conventional MRI in 13 MS patients and selected 48 juxtacortical lesions. At the first reading session with the conventional MRI alone (T2-weighted imaging, and two-dimensional and three dimensional fluid-attenuated inversion recovery), two other neuroradiologists classified the lesions into three patterns according to their anatomical locations: (a) subcortical WM lesions involving the subcortical WM alone; (b) intracortical (IC) lesions involving the GM alone; (c) mixed GM/subcortical WM (mixed) lesions involving the both subcortical WM and GM. We defined the subcortical WM as a WM within a distance of 10 mm from inner edge of the GM. For the analyses, we excluded the white matter lesions further than 10 mm from inner edge of the GM. At the second reading session MRI and PADRE were available and the radiologists re-evaluated their prior classification. RESULTS: At the first reading session, 27 lesions were classified as (a), 1 as (b), and 20 as (c). Therefore, a total of 21 lesions (44%) were judged to involve the GM. At the second reading session, the classification of 15 (31%) lesions changed; all 15 lesions were judged to involve the GM on the PADRE. Interobserver agreement (kappa value) was 0.84 for the first- and 0.95 for the second reading session. CONCLUSION: PADRE is useful for detecting GM involvement of the juxtacortical MS lesions. PMID- 26841858 TI - Speech perception scores in cochlear implant recipients: An analysis of ceiling effects in the CUNY sentence test (Quiet) in post-lingually deafened cochlear implant recipients. AB - OBJECTIVES: To evaluate the clinical utility of the City University of New York sentence test in a cohort of post-lingually deafened cochlear implants recipients over time. METHODS: 117 post-lingually deafened, Australian English-speaking CI recipients aged between 23 and 98 years (M = 66 years; SD = 15.09) were recruited. CUNY sentence test scores in quiet were collated and analysed at two cut-offs, 95% and 100%, as ceiling scores. RESULTS: CUNY sentence scores ranged from 4% to 100% (M = 86.75; SD = 20.65), with 38.8% of participants scoring 95% and 16.5% of participants reaching the 100% scores. The percentage of participants reaching the 95% and 100% ceiling scores increased over time (6 and 12 months post-implantation). The distribution of all post-operative CUNY test scores skewed to the right with 82% of test scores reaching above 90%. DISCUSSION: This study demonstrates that the CUNY test cannot be used as a valid tool to measure the speech perception skills of post-lingually deafened CI recipients over time. This may be overcome by using adaptive test protocols or linguistically, cognitively or contextually demanding test materials. CONCLUSION: The high percentage of CI recipients achieving ceiling scores for the CUNY sentence test in quiet at 3 months post-implantation, questions the validity of using CUNY in CI assessment test battery and limits its application for use in longitudinal studies evaluating CI outcomes. Further studies are required to examine different methods to overcome this problem. PMID- 26841857 TI - Cochlear Lymph Fluid Signal Increase in Patients with Otosclerosis after Intravenous Administration of Gadodiamide. AB - PURPOSE: Increased cochlear lymph fluid signals on three-dimensional fluid attenuated inversion recovery (3D-FLAIR) images obtained several minutes after intravenous administration of a single dose of gadolinium-based contrast agent (IV-SD-GBCA) in a patient with severe retrofenestral type otosclerosis had been reported. This increase was thought to represent breakdown of the blood labyrinthine barrier. The purpose of this study was to evaluate cochlear lymph signal on heavily T2-weighted 3D-FLAIR (HF) images obtained 4 hours after IV-SD GBCA in patients with otosclerosis, Meniere's disease, and healthy subjects. MATERIALS AND METHODS: Twenty-two ears from 12 patients with otosclerotic plaques determined by computed tomography (CT), 16 ears from 8 healthy volunteers, and 10 ears from 9 Meniere's disease patients with significant endolymphatic hydrops on magnetic resonance (MR) images were retrospectively analyzed. Images were obtained 4 hours after IV-SD-GBCA. Patients and healthy volunteers underwent MR cisternography (MRC) for anatomical reference of the fluid space and HF at 3T. The region of interest (ROI) was manually drawn on MRC images around the scala tympani in the basal cochlear turn. The reference ROI was set in the cerebellum. ROIs were copied onto HF images and the signal intensity ratio (SIR) of cochlear perilymph to cerebellum was measured. Differences in the SIR on HF images among the three groups were tested by one-way analysis of variance (ANOVA). RESULTS: The mean SIR was 24.0 +/- 10.1 in otosclerosis patients, 7.9 +/- 1.5 in volunteers, and 11.6 +/- 3.9 in Meniere's disease patients. The mean SIR was significantly higher in the otosclerosis group than in the other groups (P < 0.001). In the otosclerosis group, there was a significant difference in the SIR between the retrofenestral type and the fenestral type (P = 0.033). CONCLUSIONS: In patients with otosclerosis, the SIR was higher than in Meniere's disease patients or in healthy volunteers. The SIR was higher in the retrofenestral type than in the fenestral type. PMID- 26841861 TI - Engaging Active Bystanders in Mass Casualty Events and Other Life-Threatening Emergencies: A Pilot Training Course Demonstration. AB - Emerging research indicates the critical role members of the public can play in saving lives and reducing morbidity at the scene in the immediate aftermath of a disaster. It is anticipated that with training, more members of the public will be ready and able to assist should they be present at mass casualty events or other circumstances in which there are serious injuries or potential loss of life. This article describes a training course developed by multiple federal and nonfederal partners aimed at preparing the public to become "active bystanders" followed by a pilot demonstration project conducted by Medical Reserve Corps Units. The outcomes of the project indicated that the training was comprehensive and appropriate for members of the public with little or no first aid knowledge. National availability of the "Becoming an Active Bystander" training course is currently being planned. PMID- 26841856 TI - Repeatability of Brain Volume Measurements Made with the Atlas-based Method from T1-weighted Images Acquired Using a 0.4 Tesla Low Field MR Scanner. AB - PURPOSE: An understanding of the repeatability of measured results is important for both the atlas-based and voxel-based morphometry (VBM) methods of magnetic resonance (MR) brain volumetry. However, many recent studies that have investigated the repeatability of brain volume measurements have been performed using static magnetic fields of 1-4 tesla, and no study has used a low-strength static magnetic field. The aim of this study was to investigate the repeatability of measured volumes using the atlas-based method and a low-strength static magnetic field (0.4 tesla). MATERIALS AND METHODS: Ten healthy volunteers participated in this study. Using a 0.4 tesla magnetic resonance imaging (MRI) scanner and a quadrature head coil, three-dimensional T1-weighted images (3D T1WIs) were obtained from each subject, twice on the same day. VBM8 software was used to construct segmented normalized images [gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) images]. The regions-of-interest (ROIs) of GM, WM, CSF, hippocampus (HC), orbital gyrus (OG), and cerebellum posterior lobe (CPL) were generated using WFU PickAtlas. The percentage change was defined as[100 * (measured volume with first segmented image - mean volume in each subject)/(mean volume in each subject)]The average percentage change was calculated as the percentage change in the 6 ROIs of the 10 subjects. RESULTS: The mean of the average percentage changes for each ROI was as follows: GM, 0.556%; WM, 0.324%; CSF, 0.573%; HC, 0.645%; OG, 1.74%; and CPL, 0.471%. The average percentage change was higher for the orbital gyrus than for the other ROIs. CONCLUSION: We consider that repeatability of the atlas-based method is similar between 0.4 and 1.5 tesla MR scanners. To our knowledge, this is the first report to show that the level of repeatability with a 0.4 tesla MR scanner is adequate for the estimation of brain volume change by the atlas-based method. PMID- 26841862 TI - Sorting Motifs in the Cytoplasmic Tail of the Immunomodulatory E3/49K Protein of Species D Adenoviruses Modulate Cell Surface Expression and Ectodomain Shedding. AB - The E3 transcription unit of human species C adenoviruses (Ads) encodes immunomodulatory proteins that mediate direct protection of infected cells. Recently, we described a novel immunomodulatory function for E3/49K, an E3 protein uniquely expressed by species D Ads. E3/49K of Ad19a/Ad64, a serotype that causes epidemic keratokonjunctivitis, is synthesized as a highly glycosylated type I transmembrane protein that is subsequently cleaved, resulting in secretion of its large ectodomain (sec49K). sec49K binds to CD45 on leukocytes, impairing activation and functions of natural killer cells and T cells. E3/49K is localized in the Golgi/trans-Golgi network (TGN), in the early endosomes, and on the plasma membrane, yet the cellular compartment where E3/49K is cleaved and the protease involved remained elusive. Here we show that TGN localized E3/49K comprises both newly synthesized and recycled molecules. Full length E3/49K was not detected in late endosomes/lysosomes, but the C-terminal fragment accumulated in this compartment at late times of infection. Inhibitor studies showed that cleavage occurs in a post-TGN compartment and that lysosomotropic agents enhance secretion. Interestingly, the cytoplasmic tail of E3/49K contains two potential sorting motifs, YXXPhi (where Phi represents a bulky hydrophobic amino acid) and LL, that are important for binding the clathrin adaptor proteins AP-1 and AP-2in vitro Surprisingly, mutating the LL motif, either alone or together with YXXPhi, did not prevent proteolytic processing but increased cell surface expression and secretion. Upon brefeldin A treatment, cell surface expression was rapidly lost, even for mutants lacking all known endocytosis motifs. Together with immunofluorescence data, we propose a model for intracellular E3/49K transport whereby cleavage takes place on the cell surface by matrix metalloproteases. PMID- 26841863 TI - Simultaneous Activation of Induced Heterodimerization between CXCR4 Chemokine Receptor and Cannabinoid Receptor 2 (CB2) Reveals a Mechanism for Regulation of Tumor Progression. AB - The G-protein-coupled chemokine receptor CXCR4 generates signals that lead to cell migration, cell proliferation, and other survival mechanisms that result in the metastatic spread of primary tumor cells to distal organs. Numerous studies have demonstrated that CXCR4 can form homodimers or can heterodimerize with other G-protein-coupled receptors to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor. Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells. Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2 and ultimately reduced cancer cell functions such as calcium mobilization and cellular chemotaxis. Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells as well as CXCR4-mediated migration of immune cells, it is plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4. Taken together, the data illustrate a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function and perhaps tumor progression. PMID- 26841864 TI - Increased Energy Expenditure, Ucp1 Expression, and Resistance to Diet-induced Obesity in Mice Lacking Nuclear Factor-Erythroid-2-related Transcription Factor-2 (Nrf2). AB - The NRF2 (also known as NFE2L2) transcription factor is a critical regulator of genes involved in defense against oxidative stress. Previous studies suggest thatNrf2plays a role in adipogenesisin vitro, and deletion of theNrf2gene protects against diet-induced obesity in mice. Here, we demonstrate that resistance to diet-induced obesity inNrf2(-/-)mice is associated with a 20-30% increase in energy expenditure. Analysis of bioenergetics revealed thatNrf2(-/ )white adipose tissues exhibit greater oxygen consumption. White adipose tissue showed a >2-fold increase inUcp1gene expression. Oxygen consumption is also increased nearly 2.5-fold inNrf2-deficient fibroblasts. Oxidative stress induced by glucose oxidase resulted in increasedUcp1expression. Conversely, antioxidant chemicals (such asN-acetylcysteine and Mn(III)tetrakis(4-benzoic acid)porphyrin chloride) and SB203580 (a known suppressor ofUcp1expression) decreasedUcp1and oxygen consumption inNrf2-deficient fibroblasts. These findings suggest that increasing oxidative stress by limitingNrf2function in white adipocytes may be a novel means to modulate energy balance as a treatment of obesity and related clinical disorders. PMID- 26841865 TI - PAK4 Methylation by SETD6 Promotes the Activation of the Wnt/beta-Catenin Pathway. AB - Lysine methylation of non-histone proteins has emerged as a key regulator of many cellular functions. Although less studied than other post-translational modifications such as phosphorylation and acetylation, the number of known methylated non-histone proteins is rapidly expanding. We have identified the p21 activated kinase 4 (PAK4) as a new substrate for methylation by the protein lysine methyltransferase SETD6. Our data demonstrate that SETD6 methylates PAK4 bothin vitroand at chromatin in cells. Interestingly, depletion of SETD6 in various cellular systems significantly hinders the activation of the Wnt/beta catenin target genes. PAK4 was recently shown to regulate beta-catenin signaling, and we show that SETD6 is a key mediator of this pathway. In the presence of SETD6, the physical interaction between PAK4 and beta-catenin is dramatically increased, leading to a significant increase in the transcription of beta-catenin target genes. Taken together, our results uncover a new regulatory layer of the Wnt/beta-catenin signaling cascade and provide new insight into SETD6 biology. PMID- 26841866 TI - Recruitment of the Mammalian Histone-modifying EMSY Complex to Target Genes Is Regulated by ZNF131. AB - Recent work from others and us revealed interactions between the Sin3/HDAC complex, the H3K4me3 demethylase KDM5A, GATAD1, and EMSY. Here, we characterize the EMSY/KDM5A/SIN3B complex in detail by quantitative interaction proteomics and ChIP-sequencing. We identify a novel substoichiometric interactor of the complex, transcription factor ZNF131, which recruits EMSY to a large number of active, H3K4me3 marked promoters. Interestingly, using an EMSY knock-out line and subsequent rescue experiments, we show that EMSY is in most cases positively correlated with transcriptional activity of its target genes and stimulates cell proliferation. Finally, by immunohistochemical staining of primary breast tissue microarrays we find that EMSY/KDM5A/SIN3B complex subunits are frequently overexpressed in primary breast cancer cases in a correlative manner. Taken together, these data open venues for exploring the possibility that sporadic breast cancer patients with EMSY amplification might benefit from epigenetic combination therapy targeting both the KDM5A demethylase and histone deacetylases. PMID- 26841867 TI - Structural Studies of the Nedd4 WW Domains and Their Selectivity for the Connexin43 (Cx43) Carboxyl Terminus. AB - Neuronal precursor cell-expressed developmentally down-regulated 4 (Nedd4) was the first ubiquitin protein ligase identified to interact with connexin43 (Cx43), and its suppressed expression results in accumulation of gap junction plaques at the plasma membrane. Nedd4-mediated ubiquitination of Cx43 is required to recruit Eps15 and target Cx43 to the endocytic pathway. Although the Cx43 residues that undergo ubiquitination are still unknown, in this study we address other unresolved questions pertaining to the molecular mechanisms mediating the direct interaction between Nedd4 (WW1-3 domains) and Cx43 (carboxyl terminus (CT)). All three WW domains display a similar three antiparallel beta-strand structure and interact with the same Cx43CT(283)PPXY(286)sequence. Although Tyr(286)is essential for the interaction, MAPK phosphorylation of the preceding serine residues (Ser(P)(279)and Ser(P)(282)) increases the binding affinity by 2-fold for the WW domains (WW2 > WW3 ? WW1). The structure of the WW2.Cx43CT(276 289)(Ser(P)(279), Ser(P)(282)) complex reveals that coordination of Ser(P)(282)with the end of beta-strand 3 enables Ser(P)(279)to interact with the back face of beta-strand 3 (Tyr(286)is on the front face) and loop 2, forming a horseshoe-shaped arrangement. The close sequence identity of WW2 with WW1 and WW3 residues that interact with the Cx43CT PPXY motif and Ser(P)(279)/Ser(P)(282)strongly suggests that the significantly lower binding affinity of WW1 is the result of a more rigid structure. This study presents the first structure illustrating how phosphorylation of the Cx43CT domain helps mediate the interaction with a molecular partner involved in gap junction regulation. PMID- 26841870 TI - Cooperation of Sox4 with beta-catenin/p300 complex in transcriptional regulation of the Slug gene during divergent sarcomatous differentiation in uterine carcinosarcoma. AB - BACKGROUND: Uterine carcinosarcoma (UCS) represents a true example of cancer associated with epithelial-mesenchymal transition (EMT), which exhibits cancer stem cell (CSC)-like traits. Both Sox and beta-catenin signal transductions play key roles in the regulation of EMT/CSC properties, but little is known about their involvement in UCS tumorigenesis. Herein, we focused on the functional roles of the Sox/beta-catenin pathway in UCSs. METHODS: EMT/CSC tests and transfection experiments were carried out using three endometrial carcinoma (Em Ca) cell lines. Immunohistochemical investigation was also applied for a total of 32 UCSs. RESULTS: Em Ca cells cultured in STK2, a serum-free medium for mesenchymal stem cells, underwent changes in morphology toward an EMT appearance through downregulation of E-cadherin, along with upregulation of Slug, known as a target gene of beta-catenin. The cells also showed CSC properties with an increase in the aldehyde dehydrogenase (ALDH) 1(high) activity population and spheroid formation, as well as upregulation of Sox4, Sox7, and Sox9. Of these Sox factors, overexpression of Sox4 dramatically led to transactivation of the Slug promoter, and the effects were further enhanced by cotransfection of Sox7 or Sox9. Sox4 was also able to promote beta-catenin-mediated transcription of the Slug gene through formation of transcriptional complexes with beta-catenin and p300, independent of TCF4 status. In clinical samples, both nuclear beta-catenin and Slug scores were significantly higher in the sarcomatous elements as compared to carcinomatous components in UCSs, and were positively correlated with Sox4, Sox7, and Sox9 scores. CONCLUSIONS: These findings suggested that Sox4, as well as Sox7 and Sox9, may contribute to regulation of EMT/CSC properties to promote development of sarcomatous components in UCSs through transcriptional regulation of the Slug gene by cooperating with the beta-catenin/p300 signal pathway. PMID- 26841869 TI - Ikaros Is a Negative Regulator of B1 Cell Development and Function. AB - B1 B cells secrete most of the circulating natural antibodies and are considered key effector cells of the innate immune response. However, B1 cell-associated antibodies often cross-react with self-antigens, which leads to autoimmunity, and B1 cells have been implicated in cancer. How B1 cell activity is regulated remains unclear. We show that the Ikaros transcription factor is a major negative regulator of B1 cell development and function. Using conditional knock-out mouse models to delete Ikaros at different locations, we show that Ikaros-deficient mice exhibit specific and significant increases in splenic and bone marrow B1 cell numbers, and that the B1 progenitor cell pool is increased ~10-fold in the bone marrow. Ikaros-null B1 cells resemble WT B1 cells at the molecular and cellular levels, but show a down-regulation of signaling components important for inhibiting proliferation and immunoglobulin production. Ikaros-null B1 cells hyper-react to TLR4 stimulation and secrete high amounts of IgM autoantibodies. These results indicate that Ikaros is required to limit B1 cell homeostasis in the adult. PMID- 26841868 TI - Prostaglandins from Cytosolic Phospholipase A2alpha/Cyclooxygenase-1 Pathway and Mitogen-activated Protein Kinases Regulate Gene Expression in Candida albicans infected Macrophages. AB - In Candida albicans-infected resident peritoneal macrophages, activation of group IVA cytosolic phospholipase A2(cPLA2alpha) by calcium- and mitogen-activated protein kinases triggers the rapid production of prostaglandins I2 and E2 through cyclooxygenase (COX)-1 and regulates gene expression by increasing cAMP. InC. albicans-infected cPLA2alpha(-/-)or COX-1(-/-)macrophages, expression ofI l10,Nr4a2, and Ptgs2 was lower, and expression ofTnfalpha was higher, than in wild type macrophages. Expression was reconstituted with 8-bromo-cAMP, the PKA activator 6-benzoyl-cAMP, and agonists for prostaglandin receptors IP, EP2, and EP4 in infected but not uninfected cPLA2alpha(-/-)or COX-1(-/-)macrophages. InC. albicans-infected cPLA2alpha(+/+)macrophages, COX-2 expression was blocked by IP, EP2, and EP4 receptor antagonists, indicating a role for both prostaglandin I2 and E2 Activation of ERKs and p38, but not JNKs, by C. albicansacted synergistically with prostaglandins to induce expression of Il10,Nr4a2, and Ptgs2. Tnfalpha expression required activation of ERKs and p38 but was suppressed by cAMP. Results using cAMP analogues that activate PKA or Epacs suggested that cAMP regulates gene expression through PKA. However, phosphorylation of cAMP response element-binding protein (CREB), the cAMP-regulated transcription factor involved inIl10,Nr4a2,Ptgs2, andTnfalpha expression, was not mediated by cAMP/PKA because it was similar inC. albicans-infected wild type and cPLA2alpha(-/-)or COX 1(-/-)macrophages. CREB phosphorylation was blocked by p38 inhibitors and induced by the p38 activator anisomycin but not by the PKA activator 6-benzoyl-cAMP. Therefore, MAPK activation inC. albicans-infected macrophages plays a dual role by promoting the cPLA2alpha/prostaglandin/cAMP/PKA pathway and CREB phosphorylation that coordinately regulate immediate early gene expression. PMID- 26841871 TI - Chromosomal disruption and rearrangements during murine sarcoma development converge to stable karyotypic formation kept by telomerase overexpression. AB - BACKGROUND: Tumor initiation presents a complex and unstable genomic landscape; one of the earliest hallmark events of cancer, and its progression is probably based on selection mechanisms under specific environments that lead to functional tumor cell speciation. We hypothesized that viable tumor phenotypes possess common and highly stable karyotypes and their proliferation is facilitated by an attuned high telomerase activity. Very few investigations have focused on the evolution of common chromosomal rearrangements associated to molecular events that result in functional phenotypes during tumor development. RESULTS: We have used cytogenetic, flow cytometry and cell culture tools to investigate chromosomal rearrangements and clonality during cancer development using the murine sarcoma TG180 model, and also molecular biology techniques to establish a correlation between chromosome instability and telomerase activity, since telomeres are highly affected during cancer evolution. Cytogenetic analysis showed a near-tetraploid karyotype originated by endoreduplication. Chromosomal rearrangements were random events in response to in vitro conditions, but a stable karyotypic equilibrium was achieved during tumor progression in different in vivo conditions, suggesting that a specific microenvironment may stabilize the chromosomal number and architecture. Specific chromosome aberrations (marker chromosomes) and activated regions (rDNAs) were ubiquitous in the karyotype, suggesting that the conservation of these patterns may be advantageous for tumor progression. High telomerase expression was also correlated with the chromosomal rearrangements stabilization. CONCLUSIONS: Our data reinforce the notion that the sarcoma cell evolution converges from a highly unstable karyotype to relatively stable and functional chromosome rearrangements, which are further enabled by telomerase overexpression. PMID- 26841872 TI - CD146+ mesenchymal stem cells display greater therapeutic potential than CD146- cells for treating collagen-induced arthritis in mice. AB - BACKGROUND: The characteristics and therapeutic potential of subtypes of mesenchymal stem cells (MSCs) are largely unknown. In this study, CD146(+) and CD146(-) MSCs were separated from human umbilical cords, and their effects on regulatory T cells (Tregs), Th17 cells, chondrogenesis, and osteogenesis were investigated. METHODS: Flow cytometry was used to quantify IL-6 and TGF-beta1 expressed on CD146(+) and CD146(-) MSCs. The therapeutic potential of both subpopulations was determined by measuring the clinical score and joint histology after intra-articular (IA) transfer of the cells into mice with collagen-induced arthritis (CIA). RESULTS: Compared with CD146(-) MSCs, CD146(+) MSCs expressed less IL-6 and had a significantly greater effect on chondrogenesis. After T lymphocyte activation, Th17 cells were activated when exposed to CD146(-) cells but not when exposed to CD146(+) cells both in vitro and in vivo. IA injection of CD146(+) MSCs attenuated the progression of CIA. Immunohistochemistry showed that only HLA-A(+) CD146(+) cells were detected in the cartilage of CIA mice. These cells may help preserve proteoglycan expression. CONCLUSIONS: This study suggests that CD146(+) cells have greater potency than CD146(-) cells for cartilage protection and can suppress Th17 cell activation. These data suggest a potential therapeutic application for CD146(+) cells in treating inflammatory arthritis. PMID- 26841874 TI - Oxidised palm oil and sucrose induced hyperglycemia in normal rats: effects of Sclerocarya birrea stem barks aqueous extract. AB - BACKGROUND: Consumption of foods rich in carbohydrates and fats, result in an increase in obesity and consequently type 2 diabetes. The present study was carried out to evaluate the effects of oxidised palm oil and sucrose (SOPO +S) on some metabolic parameters and to investigate the effects of aqueous extract from barks of Sclerocarrya birrea on SOPO + S induced damages. METHODS: During 16 weeks, animals received every day a supplement of oxidised palm oil (10 %) and 10 % sucrose as drinking water). Control rat received standard diet and drinking water without sucrose. At the end of this period, animal presenting intolerance in glucose test and insensitivity to insulin were continuously feed with hypercaloric diet along with the administration of the plant extract (150 or 300 mg/kg) or glibenclamide (10 mg/kg) during three weeks. OGTT was performed; insulin sensitivity was assessed by performing insulin tolerance test and determining insulin sensitivity index (Kitt). Several parameters were evaluated including body weight, abdominal fat mass, blood glucose levels, blood pressure, serum lipid profile, and serum transaminases (ALT and AST). Oxidative parameters were measured by MDA levels, nitrites levels, SOD levels, reduced glutathione content and by enzyme activities of SOD and catalase. RESULTS: Animal receiving a supplement of oxidised palm oil and sucrose showed hyperglycaemia, glucose intolerance, insulin resistance and a significant increase in body weight and abdominal fat mass compared to normal rats. In addition, there was a significant increase of SOD in aorta and heart, nitrites in liver and kidney, malondialdehyde (MDA) in heart, liver and kidney. It was also observed a significant reduction in the activities of the SOD and catalase in liver, kidney and reduced glutathione levels in heart. Concomitant treatment of plant extract with SOPO + S brought glycaemia and blood pressure towards normal value, restored glucose tolerance and insulin sensitivity. The plant extract prevent the increase or decrease in the activity of the enzyme depending to the organ, reduced MDA and nitrites levels. CONCLUSION: These results highlighted the hyperglycaemic and oxidant character of SOPO + S diet and confirm the hypoglycaemic, and antioxidant action of sclerocarya birrea aqueous extract in diabetes. PMID- 26841873 TI - Functional and evolutionary analyses of the miR156 and miR529 families in land plants. AB - BACKGROUND: MicroRNAs (miRNAs) are important regulatory elements of gene expression. Similarly to coding genes, miRNA genes follow a birth and death pattern of evolution likely reflecting functional relevance and divergence. For instance, miRNA529 is evolutionarily related to miRNA156 (a highly conserved miRNA in land plants), but it is lost in Arabidopsis thaliana. Interestingly, both miRNAs target sequences overlap in some members of the SQUAMOSA promoter binding protein like (SPL) family, raising important questions regarding the diversification of the miR156/miR529-associated regulatory network in land plants. RESULTS: In this study, through phylogenic reconstruction of miR156/529 target sequences from several taxonomic groups, we have found that specific eudicot SPLs, despite miRNA529 loss, retained the corresponding target site. Detailed molecular evolutionary analyses of miR156/miR529-target sequence showed that loss of miR529 in core eudicots, such as Arabidopsis, is correlated with a more relaxed selection of the miRNA529 specific target element, while miRNA156 specific target sequence is under stronger selection, indicating that these two target sites might be under distinct evolutionary constraints. Importantly, over expression in Arabidopsis of MIR529 precursor from a monocot, but not from a basal eudicot, demonstrates specific miR529 regulation of AtSPL9 and AtSPL15 genes, which contain conserved responsive elements for both miR156 and miR529. CONCLUSIONS: Our results suggest loss of functionality of MIR529 genes in the evolutionary history of eudicots and show that the miR529-responsive element present in some eudicot SPLs is still functional. Our data support the notion that particular miRNA156 family members might have compensated for the loss of miR529 regulation in eudicot species, which concomitantly may have favored diversification of eudicot SPLs. PMID- 26841876 TI - Stakeholder perceptions and operational barriers in the training and distribution of take-home naloxone within prisons in England. AB - BACKGROUND: The aim of the study was to assess potential barriers and challenges to the implementation of take-home naloxone (THN) across ten prisons in one region of England. METHODS: Qualitative interviews deploying a grounded theory approach were utilised over a 12- to 18-month period that included an on-going structured dialogue with strategic and operational prison staff from the ten prisons and other key stakeholders (n = 17). Prisoner perceptions were addressed through four purposive focus groups belonging to different establishments (n = 26). Document analysis also included report minutes and access to management information and local performance reports. The data were thematically interpreted using visual mapping techniques. RESULTS: The distribution and implementation of THN in a prison setting was characterised by significant barriers and challenges. As a result, four main themes were identified: a wide range of negative and confused perceptions of THN amongst prison staff and prisoners; inherent difficulties with the identification and engagement of eligible prisoners; the need to focus on individual prison processes to enhance the effective distribution of THN; and the need for senior prison staff engagement. CONCLUSIONS: The distribution of THN within a custodial setting requires consideration of a number of important factors which are discussed. PMID- 26841875 TI - Interpersonal psychotherapy for depression and posttraumatic stress disorder among HIV-positive women in Kisumu, Kenya: study protocol for a randomized controlled trial. AB - BACKGROUND: Mental disorders are the leading global cause of years lived with disability; the majority of this burden exists in low and middle income countries (LMICs). Over half of mental illness is attributable to depression and anxiety disorders, both of which have known treatments. While the scarcity of mental health care providers is recognized as a major contributor to the magnitude of untreated disorders in LMICs, studies in LMICs find that evidence-based treatments for depression and anxiety disorders, such as brief, structured psychotherapies, are feasible, acceptable and have strong efficacy when delivered by local non-specialist personnel. However, most mental health treatment studies using non-specialist providers in LMICs deploy traditional efficacy designs (T1) without the benefit of integrated mental health treatment models shown to succeed over vertical interventions or methods derived from new implementation science to speed policy change. Here, we describe an effectiveness-implementation hybrid study that evaluates non-specialist delivery of mental health treatment within an HIV clinic for HIV-positive (HIV+) women affected by gender- based violence (GBV) (HIV+ GBV+) in the Nyanza region of Kenya. METHODS/DESIGN: In this effectiveness implementation hybrid type I design, 200 HIV+ women with major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) who are receiving care at a Family AIDS Care Education and Services (FACES)-supported clinic in Kisumu, Kenya will be randomized to: (1) interpersonal psychotherapy (IPT) + treatment as usual (TAU) or (2) TAU, both delivered within the HIV clinic. IPT will consist of 12 weekly 60-minute individual IPT sessions, delivered by non-specialists trained to provide IPT. Primary effectiveness outcomes will include MDD and PTSD diagnosis on the Mini International Diagnostic Interview (MINI). Primary implementation outcomes will include treatment cost-benefit, acceptability, appropriateness, feasibility and fidelity of the IPT delivery within an HIV clinic. DISCUSSION: This trial leverages newly defined effectiveness implementation hybrid designs to gather data on mental health treatment implementation within an HIV care clinic, while testing the effectiveness of an evidence-based treatment for use with a large underserved population (HIV+ GBV+ women) in Kenya. TRIAL REGISTRATION: CLINICAL TRIALS IDENTIFIER: NCT02320799, registered on 9 September 2014. PMID- 26841878 TI - Macrophages promote vasculogenesis of retinal neovascularization in an oxygen induced retinopathy model in mice. AB - To investigate the role of macrophages in oxygen-induced retinal neovascularization (NV) in mice, particularly the involvement of bone marrow derived cells (BMCs) and the underlying mechanisms, BMCs from green fluorescent protein (GFP) transgenic mice were transplanted into postnatal day (P) 1 mice after irradiation. The mice were exposed to 75 % oxygen from P7 to P12 to initiate oxygen-induced retinopathy (OIR). The macrophages were depleted by injection of clodronate-liposomes (lip) intraperitoneally. The eyes were collected at P12 and P17. Retinal flatmounts and histopathological cross-sections were performed to analyze the severity of retinal NV and BMC recruitment. BMCs immunopositive for CD31 (PECAM-1; endothelial cell marker) and alpha-SMA (smooth muscle cell marker) antigens were detected using a confocal microscope. Expression of vascular endothelial growth factor (VEGF) and stromal cell-derived factor-1 (SDF-1) mRNA was detected by RT-PCR. The VEGF, SDF-1, CXCR4 and CD45 protein expression was detected by western blot examination. The retinal avascular area in OIR mice at P12 was unaffected after macrophage depletion carried out twice (38.27 +/- 1.92 % reduction) using clodronate-lip. The retinal avascular area and the NV area at P17 were reduced after macrophage depletion four times (79.53 +/- 1.02 % reduction); these findings were supported by retinal flatmounts and histopathological cross-sections. Macrophage depletion led to significant inhibition of BMC recruitment into the NV tufts at P17, with decreased expression of retinal VEGF, SDF-1, CXCR4 and CD45. The recruited BMCs differentiated primarily into CD31-positive endothelial cells (ECs) and alpha-SMA positive smooth muscle cells (SMCs). This study suggested that macrophages promoted the vasculogenesis of retinal NV, particularly the contribution of BMCs in the mouse OIR model, which might be triggered by VEGF and SDF-1 production. PMID- 26841877 TI - Bridging the gap between pragmatic intervention design and theory: using behavioural science tools to modify an existing quality improvement programme to implement "Sepsis Six". AB - BACKGROUND: Sepsis has a mortality rate of 40 %, which can be halved if the evidence-based "Sepsis Six" care bundle is implemented within 1 h. UK audit shows low implementation rates. Interventions to improve this have had minimal effects. Quality improvement programmes could be further developed by using theoretical frameworks (Theoretical Domains Framework (TDF)) to modify existing interventions by identifying influences on clinical behaviour and selecting appropriate content. The aim of this study was to illustrate using this process to modify an intervention designed using plan-do-study-act (P-D-S-A) cycles that had achieved partial success in improving Sepsis Six implementation in one hospital. METHODS: Factors influencing implementation were investigated using the TDF to analyse interviews with 34 health professionals. The nursing team who developed and facilitated the intervention used the data to select modifications using the Behaviour Change Technique (BCT) Taxonomy (v1) and the APEASE criteria: affordability, practicability, effectiveness, acceptability, safety and equity. RESULTS: Five themes were identified as influencing implementation and guided intervention modification. These were:(1) "knowing what to do and why" (TDF domains knowledge, social/professional role and identity); (2) "risks and benefits" (beliefs about consequences), e.g. fear of harming patients through fluid overload acting as a barrier to implementation versus belief in the bundle's effectiveness acting as a lever to implementation; (3) "working together" (social influences, social/professional role and identity), e.g. team collaboration acting as a lever versus doctor/nurse conflict acting as a barrier; (4) "empowerment and support" (beliefs about capabilities, social/professional role and identity, behavioural regulation, social influences), e.g. involving staff in intervention development acting as a lever versus lack of confidence to challenge colleagues' decisions not to implement acting as a barrier; (5) "staffing levels" (environmental context and resources), e.g. shortages of doctors at night preventing implementation. The modified intervention included six new BCTs and consisted of two additional components (Sepsis Six training for the Hospital at Night Co-ordinator; a partnership agreement endorsing engagement of all clinical staff and permitting collegial challenge) and modifications to two existing components (staff education sessions; documents and materials). CONCLUSIONS: This work demonstrates the feasibility of the TDF and BCT Taxonomy (v1) for developing an existing quality improvement intervention. The tools are compatible with the pragmatic P-D-S-A cycle approach generally used in quality improvement work. PMID- 26841880 TI - Legal Issues in Quarantine and Isolation for Control of Emerging Infectious Diseases. AB - The Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea in 2015 has drawn public attention regarding the legal regulation of infectious disease control in Korea. This paper discusses the interpretive and legislative concerns regarding the Infectious Disease Prevention and Control Act, its ordinance and enforcement regulations, as well as public statements from the relevant administrative agency. Future improvements are also proposed. PMID- 26841881 TI - Ethical Perspectives on the Middle East Respiratory Syndrome Coronavirus Epidemic in Korea. AB - Ethical considerations are essential in planning for and responding to outbreaks of infectious diseases. During the outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in the Republic of Korea in 2015, serious challenges emerged regarding important ethical issues, such as transparency and the protection of privacy. The development of bioethics in Korea has been influenced by individualistic perspectives applied in clinical contexts, leading to a paucity of ethical perspectives relevant to population-level phenomena such as outbreaks. Alternative theories of public health ethics include the perspectives of relational autonomy and the patient as victim and vector. Public health actions need to incorporate clear and systematic procedures founded upon ethical principles. The MERS-CoV epidemic in Korea created significant public support for more aggressive early interventions in future outbreaks. This trend makes it all the more imperative for ethical principles and procedures to be implemented in future planning and responses to outbreaks in order to promote perceptions of legitimacy and civic participation. PMID- 26841879 TI - Exosomes derived from endometriotic stromal cells have enhanced angiogenic effects in vitro. AB - Our objective has been to establish a pro-angiogenic role for exosomes in endometriosis and to determine whether a differential expression profile of cellular and exosomal microRNAs (miRNAs) exists in endometriosis. We performed an in vitro study of human primary endometrial stromal cells (ESCs) and human umbilical vein endothelial cells (HUVECs). We isolated and characterized exosomes from ESCs from five endometriosis patients and five phase-matched controls. Exosomes were characterized by transmission electron microscopy and NanoSight technology. MiRNA was assessed by deep sequencing and reverse transcription with quantitative polymerase chain reaction. Exosome uptake studies were achieved by means of confocal microscopy. The pro-angiogenic experiments were executed by treating HUVECs with ESC-derived exosomes. We observed differential profiles of exosomal miRNA expression between exosomes derived from endometriosis lesion cells and diseased eutopic stromal cells compared with exosomes derived from control ESCs. We also demonstrated autocrine cellular uptake of exosomes and paracrine functional angiogenic effects of exosomes on HUVECs. The results of this study support the hypothesis that exosomes derived from ESCs play autocrine/paracrine roles in the development of endometriosis, potentially modulating angiogenesis. The broader clinical implications are that Sampson's theory of retrograde menstruation possibly encompasses the finding that exosomes work as intercellular communication modulators in endometriosis. PMID- 26841882 TI - The Tobacco Industry's Abuse of Scientific Evidence and Activities to Recruit Scientists During Tobacco Litigation. AB - South Korea's state health insurer, the National Health Insurance Service (NHIS), is in the process of a compensation suit against tobacco industry. The tobacco companies have habitually endeavored to ensure favorable outcomes in litigation by misusing scientific evidence or recruiting scientists to support its interests. This study analyzed strategies that tobacco companies have used during the NHIS litigation, which has been receiving world-wide attention. To understand the litigation strategies of tobacco companies, the present study reviewed the existing literature and carried out content analysis of petitions, preparatory documents, and supporting evidence submitted to the court by the NHIS and the tobacco companies during the suit. Tobacco companies misrepresented the World Health Organization (WHO) report's argument and misused scientific evidence, and removed the word "deadly" from the title of the citation. Tobacco companies submitted the research results of scientists who had worked as a consultant for the tobacco industry as evidence. Such litigation strategies employed by the tobacco companies internationally were applied similarly in Korean lawsuits. Results of tobacco litigation have a huge influence on tobacco control policies. For desirable outcomes of the suits, healthcare professionals need to pay a great deal of attention to the enormous volume of written opinions and supporting evidence that tobacco companies submit. They also need to face the fact that the companies engage in recruitment of scientists. Healthcare professionals should refuse to partner with tobacco industry, as recommended by Article 5.3 of the WHO Framework Convention on Tobacco Control. PMID- 26841883 TI - Associations of Sarcopenia and Sarcopenic Obesity With Metabolic Syndrome Considering Both Muscle Mass and Muscle Strength. AB - OBJECTIVES: We investigated the associations of sarcopenia-defined both in terms of muscle mass and muscle strength-and sarcopenic obesity with metabolic syndrome. METHODS: Secondary data pertaining to 309 subjects (85 men and 224 women) were collected from participants in exercise programs at a health center in a suburban area. Muscle mass was measured using bioelectrical impedance analysis, and muscle strength was measured via handgrip strength. Sarcopenia based on muscle mass alone was defined as a weight-adjusted skeletal muscle mass index more than two standard deviations below the mean of a sex-specific young reference group (class II sarcopenia). Two cut-off values for low handgrip strength were used: the first criteria were <26 kg for men and <18 kg for women, and the second criteria were the lowest quintile of handgrip strength among the study subjects. Sarcopenic obesity was defined as the combination of class II sarcopenia and being in the two highest quintiles of total body fat percentage among the subjects. The associations of sarcopenia and sarcopenic obesity with metabolic syndrome were evaluated using logistic regression models. RESULTS: The age-adjusted risk ratios (RRs) of metabolic syndrome being compared in people with or without sarcopenia defined in terms of muscle mass were 1.25 (95% confidence interval [CI], 1.06 to 1.47, p=0.008) in men and 1.12 (95% CI, 1.06 to 1.19, p<0.001) in women, which were found to be statistically significant relationships. The RRs of metabolic syndrome being compared in people with or without sarcopenic obesity were 1.31 in men (95% CI, 1.10 to 1.56, p=0.003) and 1.17 in women (95% CI, 1.10 to 1.25, p<0.001), which were likewise found to be statistically significant relationships. CONCLUSIONS: The associations of sarcopenia defined in terms of muscle mass and sarcopenic obesity with metabolic syndrome were statistically significant in both men and women. Therefore, sarcopenia and sarcopenic obesity must be considered as part of the community based management of non-communicable diseases. PMID- 26841884 TI - Diabetes Mellitus and Site-specific Colorectal Cancer Risk in Korea: A Case control Study. AB - OBJECTIVES: Previous large-scale cohort studies conducted in Korea have found a positive association between diabetes mellitus (DM) and colorectal cancer (CRC) in men only, in contrast to studies of other populations that have found significant associations in both men and women. METHODS: A total of 1070 CRC cases and 2775 controls were recruited from the National Cancer Center, Korea between August 2010 and June 2013. Self-reported DM history and the duration of DM were compared between cases and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by binary and polytomous logistic regression models. RESULTS: DM was associated with an elevated risk of CRC in both men (OR, 1.47; 95% CI, 1.13 to 1.90) and women (OR, 1.92; 95% CI, 1.24 to 2.98). This association remained when we controlled for age, body mass index, alcohol consumption, and physical activity level. In sub-site analyses, DM was associated with distal colon cancer risk in both men (multivariate OR, 2.04; 95% CI, 1.39 to 3.00) and women (multivariate ORs, 1.99; 95% CI, 1.05 to 3.79), while DM was only associated with rectal cancer risk in women (multivariate OR, 2.05; 95% CI, 1.10 to 3.82). No significant association was found between DM and proximal colon cancer risk in either men (multivariate OR, 1.45; 95% CI, 0.88 to 2.41) or women (multivariate OR, 1.79; 95% CI, 0.78 to 4.08). CONCLUSIONS: Overall, DM was associated with an increased risk of CRC in Koreans. However, potential over estimation of the ORs should be considered due to potential biases from the case control design. PMID- 26841885 TI - Factors Affecting the Downward Mobility of Psychiatric Patients: A Korean Study of National Health Insurance Beneficiaries. AB - OBJECTIVES: The purpose of this study is to examine the magnitude of and the factors associated with the downward mobility of first-episode psychiatric patients. METHODS: This study used the claims data from the Korean Health Insurance Review and Assessment Service. The study population included 19 293 first-episode psychiatric inpatients diagnosed with alcohol use disorder (International Classification of Diseases, 10th revision [ICD-10] code F10), schizophrenia and related disorders (ICD-10 codes F20-F29), and mood disorders (ICD-10 codes F30-F33) in the first half of 2005. This study included only National Health Insurance beneficiaries in 2005. The dependent variable was the occurrence of downward mobility, which was defined as a health insurance status change from National Health Insurance to Medical Aid. Logistic regression analysis was used to assess factors associated with downward drift of first episode psychiatric patients. RESULTS: About 10% of the study population who were National Health Insurance beneficiaries in 2005 became Medical Aid recipients in 2007. The logistic regression analysis showed that age, gender, primary diagnosis, type of hospital at first admission, regular use of outpatient clinic, and long-term hospitalization are significant predictors in determining downward drift in newly diagnosed psychiatric patients. CONCLUSIONS: This research showed that the downward mobility of psychiatric patients is affected by long-term hospitalization and medical care utilization. The findings suggest that early intensive intervention might reduce long-term hospitalization and the downward mobility of psychiatric patients. PMID- 26841886 TI - School Violence, Depressive Symptoms, and Help-seeking Behavior: A Gender stratified Analysis of Biethnic Adolescents in South Korea. AB - OBJECTIVES: In South Korea (hereafter Korea), the number of adolescent offspring of immigrants has rapidly increased since the early 1990s, mainly due to international marriage. This research sought to examine the association between the experience of school violence and mental health outcomes, and the role of help-seeking behaviors in the association, among biethnic adolescents in Korea. METHODS: We analyzed cross-sectional data of 3627 biethnic adolescents in Korea from the 2012 National Survey of Multicultural Families. Based on the victim's help-seeking behavior, adolescents who experienced school violence were classified into three groups: 'seeking help' group; 'feeling nothing' group; 'not seeking help' group. Multivariate logistic regression was applied to examine the associations between the experience of school violence and depressive symptoms for males and females separately. RESULTS: In the gender-stratified analysis, school violence was associated with depressive symptoms in the 'not seeking help' (odds ratio [OR], 7.05; 95% confidence interval [CI], 3.76 to 13.23) and the 'seeking help' group (OR, 2.77; 95% CI, 1.73 to 4.44) among male adolescents after adjusting for potential confounders, including the nationality of the immigrant parent and Korean language fluency. Similar associations were observed in the female groups. However, in the 'feeling nothing' group, the association was only significant for males (OR, 8.34; 95% CI, 2.82 to 24.69), but not females (OR, 0.77; 95% CI, 0.18 to 3.28). CONCLUSIONS: This study suggests that experience of school violence is associated with depressive symptoms and that the role of victims' help-seeking behaviors in the association may differ by gender among biethnic adolescents in Korea. PMID- 26841887 TI - Determinants of Mental Health Care Utilization in a Suicide High-risk Group With Suicidal Ideation. AB - OBJECTIVES: The suicide rate in Korea is increasing every year, and is the highest among the Organization for Economic Cooperation and Development countries. Psychiatric patients in particular have a higher risk of suicide than other patients. This study was performed to evaluate determinants of mental health care utilization among individuals at high risk for suicide. METHODS: Korea Health Panel data from 2009 to 2011 were used. Subjects were individuals at high risk of suicide who had suicidal ideation, a past history of psychiatric illness, or had utilized outpatient services for a psychiatric disorder associated with suicidal ideation within the past year. The chi-square test and hierarchical logistic regression were used to identify significant determinants of mental health care utilization. RESULTS: The total number of subjects with complete data on the variables in our model was 989. Individuals suffering from three or more chronic diseases used mental health care more frequently. Mental health care utilization was higher in subjects who had middle or high levels of educational attainment, were receiving Medical Aid, or had a large family size. CONCLUSIONS: It is important to control risk factors in high-risk groups as part of suicide prevention strategies. The clinical approach, which includes community based intervention, entails the management of reduction of suicidal risk. Our study identified demographic characteristics that have a significant impact on mental health care utilization and should be considered in the development of suicide prevention strategies. Further studies should examine the effect of mental health care utilization on reducing suicidal ideation. PMID- 26841888 TI - Continuous and interval training programs using deep water running improves functional fitness and blood pressure in the older adults. AB - This study aimed to investigate the effects of two periodized training programs of deep water running on functional fitness and blood pressure in the older adults. Thirty-six individuals were divided into continuous group (CONT) and interval group (INT). Both groups were trained for 28 weeks (twice weekly). Measures were performed before the training period, after 12 weeks and training period. Two-way ANOVA and post hoc of Bonferroni were used (alpha = 0.05). There were no differences between groups in functional tests, with the exception of the flexibility of the upper limbs, in which the INT group showed the highest values. There was a significant improvement in both groups of foot up-and-go test (CONT 6.45 to 5.67; INT 6.59 to 5.78, in seconds), flexibility of lower limbs (CONT 4.76 to -0.61; INT 0.54 to 4.63, in centimeters), strength of upper (CONT 18.76 to 27.69; INT 18.66 to 26.58, in repetitions) and lower limbs (CONT 14.46 to 21.23; INT 14.40 to 21.58, in repetitions), and 6-min walk (CONT 567.50 to 591.16; INT 521.41 to 582.77, in meters). No differences were shown between groups for systolic blood pressure; however, diastolic blood pressure remained higher in CONT during all training. The blood pressure decreased significantly in both groups after the training (CONT 142 +/- 16/88 +/- 3 to 125 +/- 14/77 +/- 7 mmHg; INT 133 +/- 15/75 +/- 7 to 123 +/- 17 and 69 +/- 11 mmHg). Both programs of deep water running training promoted improvements of similar magnitude in all parameters of functional fitness, with the exception of flexibility of upper limbs, and decreased blood pressure in the older individuals. PMID- 26841889 TI - Regulation of cell growth and apoptosis through lactate dehydrogenase C over expression in Chinese hamster ovary cells. AB - Lactate has long been credited as a by-product, which jeopardizes cell growth and productivity when accumulated over a certain concentration during the manufacturing process of therapeutic recombinant proteins by Chinese hamster ovary (CHO) cells. A number of efforts to decrease the lactate concentration have been developed; however, the accumulation of lactate is still a critical issue by the late stage of fed-batch culture. Therefore, a lactate-tolerant cell line was developed through over-expression of lactate dehydrogenase C (LDH-C). In fed batch culture, sodium lactate or sodium pyruvate was supplemented into the culture medium to simulate the environment of lactate accumulation, and LDH-C over-expression increased the highest viable cell density by over 30 and 50 %, respectively, on day 5, meanwhile the viability was also improved significantly since day 5 compared with that of the control. The percentages of cells suffering early and late apoptosis decreased by 3.2 to 12.5 and 2.0 to 4.3 %, respectively, from day 6 onwards in the fed-batch culture when 40 mM sodium pyruvate was added compared to the control. The results were confirmed by mitochondrial membrane potential assay. In addition, the expression of cleaved caspases 3 and 7 decreased in cells over-expressing LDH-C, suggesting the mitochondrial pathway was involved in the LDH-C regulated anti-apoptosis. In conclusion, a novel cell line with higher lactate tolerance, lowered lactate production, and alleviated apoptosis response was developed by over-expression of LDH-C, which may potentially represent an efficient and labor-saving approach in generating recombinant proteins. PMID- 26841890 TI - Shifts of microbial communities of wheat (Triticum aestivum L.) cultivation in a closed artificial ecosystem. AB - The microbial communities of plant ecosystems are in relation to plant growing environment, but the alteration in biodiversity of rhizosphere and phyllosphere microbial communities in closed and controlled environments is unknown. The purpose of this study is to analyze the change regularity of microbial communities with wheat plants dependent-cultivated in a closed artificial ecosystem. The microbial community structures in closed-environment treatment plants were investigated by a culture-dependent approach, polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE), and Illumina Miseq high-throughput sequencing. The results indicated that the number of microbes decreased along with time, and the magnitude of bacteria, fungi, and actinomycetes were 10(7)-10(8), 10(5), and 10(3)-10(4) CFU/g (dry weight), respectively. The analysis of PCR-DGGE and Illumina Miseq revealed that the wheat leaf surface and near-root substrate had different microbial communities at different periods of wheat ecosystem development and showed that the relative highest diversity of microbial communities appeared at late and middle periods of the plant ecosystem, respectively. The results also indicated that the wheat leaf and substrate had different microbial community compositions, and the wheat substrate had higher richness of microbial community than the leaf. Flavobacterium, Pseudomonas, Paenibacillus, Enterobacter, Penicillium, Rhodotorula, Acremonium, and Alternaria were dominant in the wheat leaf samples, and Pedobacter, Flavobacterium, Halomonas, Marinobacter, Salinimicrobium, Lysobacter, Pseudomonas, Halobacillus, Xanthomonas, Acremonium, Monographella, and Penicillium were dominant populations in the wheat near-root substrate samples. PMID- 26841891 TI - Reactions to smoke-free public policies and smoke-free home policies in the Republic of Georgia: results from a 2014 national survey. AB - OBJECTIVES: We examined receptivity to public smoke-free policies and smoke-free home status among adults in the Republic of Georgia. METHODS: In Spring 2014, we conducted a national household survey of 1163 adults. RESULTS: Our sample was on average 42.4 years old, 51.1 % male, and 43.2 % urban. Current smoking prevalence was 54.2 % in men and 6.5 % in women. Notably, 42.2 % reported daily secondhand smoke exposure (SHSe). Past week SHSe was 29.9 % in indoor public places and 33.0 % in outdoor public places. The majority reported no opposition to public smoke free policies. Correlates of greater receptivity to public policies included being older, female, and a nonsmoker. Past week SHSe in homes was 54.2 %; 38.8 % reported daily SHSe at home. Only 14.3 % reported complete smoke-free home policies; 39.0 % had partial policies. The only correlate of allowing smoking in the home was being a smoker. Among smokers, correlates of allowing smoking in the home were being male and lower confidence in quitting. CONCLUSIONS: SHSe is prevalent in various settings in Georgia, requiring efforts to promote support for public smoke-free policies and implementation of personal policies. PMID- 26841892 TI - Decreased smoking initiation among male youths in China: an urban-rural comparison. AB - OBJECTIVES: This study compared urban/rural differences in smoking initiation during the transition from adolescence to young adulthood among Chinese males. METHODS: Data were derived from the China Health and Nutrition Survey (N = 2395). Logistic and cox models were computed to assess smoking initiation between the ages of 15 and 20 across urban/rural administrative districts (i.e. urban neighborhood, suburban village, county town neighborhood, and rural village). RESULTS: Findings revealed that rates of smoking initiation decreased from the 1970 to 1996 cohorts in all four administrative districts. After adjusting for household and community characteristics, the inverse association between smoking initiation and birth year remained statistically significant (p < 0.05) in all administrative districts with the exception of urban neighborhoods. County town neighborhoods and suburban villages witnessed accelerated reductions in smoking initiation. CONCLUSIONS: Decreased smoking initiation appears to be associated with birth year, which may be correlated with social and economic development of China in conjunction with an unprecedented rate of urbanization. Results suggest that the rate of smoking initiation for male youths may experience further decreases, particularly in areas with a heightened potential of urbanization. PMID- 26841893 TI - The dynamic interdependence between family support and depressive symptoms among adolescents in Ghana. AB - OBJECTIVES: This study identified temporal sequencing in the associations between family support and depressive symptoms over the course of adolescence for youth in Ghana. METHODS: Data derived from a longitudinal cohort study of 718 Ghanaian adolescents (58 % female) who were, on average, 13.84 years at Wave 1. Youth completed surveys at three time points separated by an 18-month time lag from early through late adolescence. Latent growth curve techniques were used to investigate the degree to which family support predicts changes in youth depressive symptoms and/or depressive symptoms precede changes in family support from early through late adolescence. RESULTS: Youth in Ghana experience declines in family support and increases in depressive symptoms over the course of adolescence. The associations between lower family support and higher depressive symptoms are recursive or bidirectional over time. CONCLUSIONS: Study results suggest the value of promoting family support and reducing youth's depressive symptomology as a way of interrupting a recursive cycle of declining family support and increasing depressive symptomology from early through late adolescence. PMID- 26841894 TI - Does self-efficacy mediate the association between socioeconomic background and emotional symptoms among schoolchildren? AB - OBJECTIVES: Emotional symptoms are widespread among adolescents with the highest prevalence among lower socioeconomic groups. Less is known about why and how to reduce this inequality but personal control, e.g., self-efficacy may be crucial. This study examines whether self-efficacy is a mediator in the association between occupational social class (OSC) and emotional symptoms. METHODS: Data stem from the cross-sectional Health Behavior in School-aged Children-Methodology Development Survey 2012 (HBSC-MDS) conducted among 11-15-year old schoolchildren in two Danish municipalities. Participation rate was 76.8 % of 5165 enrolled schoolchildren, n = 3969. RESULTS: Low OSC is associated with higher odds of daily emotional symptoms and low selfefficacy. Schoolchildren with low self efficacy have higher odds for daily emotional symptoms. We find a strong and statistically significant direct effect between low OSC and daily emotional symptoms (OR = 1.55, 95 % CI: 1.33; 1.84) and a borderline statistically significant indirect effect of self-efficacy [OR = 1.17 (0.99; 1.38)]. CONCLUSIONS: Socioeconomic inequality in emotional symptoms exists. This inequality is partly explained by socioeconomic inequality in self-efficacy. Promotion of personal competences like self-efficacy may reduce emotional symptoms among all socioeconomic groups, thereby reducing socioeconomic inequalities in emotional symptoms. PMID- 26841895 TI - Vape, quit, tweet? Electronic cigarettes and smoking cessation on Twitter. AB - OBJECTIVES: Individuals seeking information about electronic cigarettes are increasingly turning to social media networks like Twitter. We surveyed dominant Twitter communications about e-cigarettes and smoking cessation, examining message sources, themes, and attitudes. METHODS: Tweets from 2014 were searched for mentions of e-cigarettes and smoking cessation. A purposive sample was subjected to mixed-methods analysis. RESULTS: Twitter communication about e cigarettes increased fivefold since 2012. In a sample of 300 tweets from high authority users, attitudes about e-cigarettes as smoking cessation aids were favorable across user types (industry, press, public figures, fake accounts, and personal users), except for public health professionals, who lacked consensus and contributed negligibly to the conversation. The most prevalent message themes were marketing, news, and first-person experiences with e-cigarettes as smoking cessation aids. We identified several industry strategies to reach Twitter users. CONCLUSIONS: Our findings show that Twitter users are overwhelmingly exposed to messages that favor e-cigarettes as smoking cessation aids, even when disregarding commercial activity. This underlines the need for effective public health engagement with social media to provide reliable information about e cigarettes and smoking cessation online. PMID- 26841897 TI - Types of Rural Extensionists' Expectations of Psychology and Their Implications on Psychologists' Practice. AB - Psychology has great potential for contributing to rural development, particularly through supporting rural extension (RE). In this paper, the types of expectations extensionists have of psychology are identified, as well as possible ways of integrating psychosocial knowledge into the RE context. Rural extensionists from 12 Latin American countries were surveyed (n = 654). Of them, 89.4 % considered psychology could contribute to rural extension and commented on how this would be possible. Expectations were categorised and the nine mentioned by more than 20 % of them were utilized to conduct a two-steps cluster analysis. Three types of extensionists' expectations were identified: one wherein working with extensionists was highlighted; another characterised by a focus on working with farmers; and a third featuring a traditional, diffusionist extension approach, which views farmers as objects of psychologists' interventions. With the first type, psychologists should not neglect working with farmers and with the second, with extensionists. With the third type, reflecting on the expectations themselves and their underlying assumptions seems essential. PMID- 26841896 TI - The specificity of Pavlovian regulation is associated with recovery from depression. AB - BACKGROUND: Changes in reflexive emotional responses are hallmarks of depression, but how emotional reflexes make an impact on adaptive decision-making in depression has not been examined formally. Using a Pavlovian-instrumental transfer (PIT) task, we compared the influence of affectively valenced stimuli on decision-making in depression and generalized anxiety disorder compared with healthy controls; and related this to the longitudinal course of the illness. METHOD: A total of 40 subjects with a current DSM-IV-TR diagnosis of major depressive disorder, dysthymia, generalized anxiety disorder, or a combination thereof, and 40 matched healthy controls performed a PIT task that assesses how instrumental approach and withdrawal behaviours are influenced by appetitive and aversive Pavlovian conditioned stimuli (CSs). Patients were followed up after 4-6 months. Analyses focused on patients with depression alone (n = 25). RESULTS: In healthy controls, Pavlovian CSs exerted action-specific effects, with appetitive CSs boosting active approach and aversive CSs active withdrawal. This action specificity was absent in currently depressed subjects. Greater action specificity in patients was associated with better recovery over the follow-up period. CONCLUSIONS: Depression is associated with an abnormal influence of emotional reactions on decision-making in a way that may predict recovery. PMID- 26841898 TI - Orbital venous pattern in relation to extraorbital venous drainage and superficial lymphatic vessels in rats. AB - The purpose of this study was to demonstrate the normal and variant anatomy of extraorbital and intraorbital venous drainage together with retroorbital communication, and determine the lymphatic drainage from the superficial orbital region with a potential outlet of lymphatic vessel into the venous bloodstream. The study of the venous system was carried out on 32 Wistar rats by using corrosion casts methods and radiography, while the lymphatic system was studied in 12 Wistar rats following ink injection. Superficially, orbital veins are connected with extraorbital veins running through angular vein of the eye and the superficial temporal vein, and via the pterygoid plexus with the maxillary vein, which provide readily accessible communication routes in the spread of infection. The extent of intraorbital and periorbital venous drainage was ensured by the dorsal and ventral external ophthalmic vein through the infraorbital vein, which together formed the principal part of the ophthalmic plexus. Venous drainage of the eyeball was carried out mainly by the vortex veins, ciliary veins and internal ophthalmic vein. The highest variability, first presented by differences in structural arrangement and formation of anastomoses, was observed within the ventral external ophthalmic vein (22 cases) and the medial vortex vein (10 cases). Four vortex veins, one vein in each quadrant of the eye, were observed in rats. The vortex vein located on the ventral side of the eyeball was occasionally found as two veins (in four cases) in the present study. The lymphatic vessel from the lower eyelid entered into the mandibular lymph centre, and from the upper eyelid entered into the superficial cervical lymph centre, but both drained into the deep cranial cervical lymph node. The direct entry of lymph entering the veins without passing through lymph nodes was not observed. PMID- 26841899 TI - Regional Variation in Diabetic Outcomes by Country-of-Origin and Language in an Urban Safety Net Hospital. AB - Adherence to diabetic care guidelines among US immigrants remains low. This study assesses adherence to diabetic care guidelines by country-of-origin and language among a limited English-proficient (LEP) population. Timely completion of diabetic measures and acceptable levels of hemoglobin A1c (A1c), low density lipoprotein (LDL) cholesterol, and blood pressure (BP) were compared between LEP and English-proficient (EP) patients in this 2013 retrospective cohort study of adult diabetics. More LEP patients met BP targets (83 vs. 68 %, p < 0.0001) and obtained LDL targets (89 vs. 85 %, p = 0.0007); however, they had worse LDL control (57 vs. 62 %, p = 0.0011). Ethiopians and Somalians [adjusted OR (95 % CI) = 0.44 (0.30, 0.63)] were less likely than Latin Americans to meet BP goals. LEP patients outperformed EP peers on several diabetic outcomes measures with important variation between groups. These data highlight the success of a safety net hospital in improving diabetes management among diverse populations. PMID- 26841900 TI - Elevated urinary Na/K ratio among Lebanese elementary school children is attributable to low K intake. AB - PURPOSE: To estimate total sodium (Na) and potassium (K) intake using non-fasting morning urine specimens among Lebanese elementary (6-10 year old) schoolchildren. METHOD: A national cross-sectional study was conducted. A multistage cluster sampling procedure was used to select a representative sample of 1403 healthy children from the eight districts of Lebanon. Age, anthropometric measurements, and urine samples were collected and analyzed for Na, K, and creatinine (Cr). RESULTS: The ratios of Na and K to Cr were 23.93 +/- 15.54 mM/mM (4.86 +/- 3.16 mg/mg) and 11.48 +/- 5.82 mM/mM (3.97 +/- 2.01 mg/mg), respectively, and showed differences (P value <0.001) between age groups. No differences were found between boys and girls in all the measured Na and K parameters. The estimated mean Na intake was 96.57 +/- 61.67 mM/day (2.220 +/- 1.418 g/day or 5.69 +/- 3.64 g NaCl/day) and exceeded the upper limit of intake in half the children. Estimated K intake was 46.6 +/- 23.02 mM/day (1.822 +/- 0.900 g/day), and almost all children failed to meet the recommended daily K intake. The high Na/K ratio (2.361 +/- 1.67 mM/mM or 1.39 +/- 0.98 mg/mg) resulted from a combination of high Na and low K intake but was mostly affected by K intake. CONCLUSIONS: About 50 % of children exceeded the recommended daily upper intake for Na, while the majority was below K adequate intake. This unfavorable Na/K ratio is indicative of potentially negative health effects at later stages in life. Interventions aimed at reducing salt intake and increasing consumption of fruits and vegetables are warranted. PMID- 26841901 TI - Broadly Neutralizing Antibodies for HIV Eradication. AB - Passive transfer of antibodies has long been considered a potential treatment modality for infectious diseases, including HIV. Early efforts to use antibodies to suppress HIV replication, however, were largely unsuccessful, as the antibodies that were studied neutralized only a relatively narrow spectrum of viral strains and were not very potent. Recent advances have led to the discovery of a large portfolio of human monoclonal antibodies that are broadly neutralizing across many HIV-1 subtypes and are also substantially more potent. These antibodies target multiple different epitopes on the HIV envelope, thus allowing for the development of antibody combinations. In this review, we discuss the application of broadly neutralizing antibodies (bNAbs) for HIV treatment and HIV eradication strategies. We highlight bNAbs that target key epitopes, such as the CD4 binding site and the V2/V3-glycan-dependent sites, and we discuss several bNAbs that are currently in the clinical development pipeline. PMID- 26841902 TI - A phase II study of cediranib, an oral VEGF inhibitor, in previously untreated patients with metastatic or recurrent malignant melanoma. AB - PURPOSE: A two stage multi-institution Phase II study was undertaken by the Princess Margaret Hospital Consortium to evaluate the efficacy and toxicity of oral cediranib, an inhibitor of vascular endothelial growth factor receptors 1 and 2, in patients with previously untreated advanced malignant melanoma. PATIENTS AND METHODS: Between May 2006 and April 2008, 24 patients (median age 65 years) with advanced malignant melanoma were treated with oral cediranib. Cediranib was given on a continuous, oral once daily schedule of 45 mg, on a 28 day cycle. RESULTS: Of the 17 patients evaluable for response, there was stable disease in 8 patients, and progressive disease in 9 patients, with no objective responses seen. Only 2 patients had stable disease >/= 6 months, thus the study was terminated at the end of stage 1 accrual. The overall median survival was 9.9 months, and the median time to progression was 3.5 months. The most frequent non hematologic adverse events were hypertension (78%), fatigue (69%), diarrhea (69%) and anorexia and nausea (each 57%). CONCLUSIONS: Although 2 patients had stable disease at 6 months, the short median time to progression and lack of any objective responses indicate that single agent cediranib at this dose and schedule is not sufficiently active to warrant study continuation. PMID- 26841903 TI - RRx-001, A novel dinitroazetidine radiosensitizer. AB - The 'holy grail' in radiation oncology is to improve the outcome of radiation therapy (RT) with a radiosensitizer-a systemic chemical/biochemical agent that additively or synergistically sensitizes tumor cells to radiation in the absence of significant toxicity. Similar to the oxygen effect, in which DNA bases modified by reactive oxygen species prevent repair of the cellular radiation damage, these compounds in general magnify free radical formation, leading to the permanent "fixation" of the resultant chemical change in the DNA structure. The purpose of this review is to present the origin story of the radiosensitizer, RRx 001, which emerged from the aerospace industry. The activity of RRx-001 as a chemosensitizer in multiple tumor types and disease states including malaria, hemorrhagic shock and sickle cell anemia, are the subject of future reviews. PMID- 26841904 TI - Amphetamine manipulates monoamine oxidase-A level and behavior using theranostic aptamers of transcription factors AP-1/NF-kB. AB - BACKGROUND: Monoamine oxidase (MAO) enzymes play a critical role in controlling the catabolism of monoamine neurotransmitters and biogenic trace amines and behavior in humans. However, the mechanisms that regulate MAO are unclear. Several transcription factor proteins are proposed to modulate the transcription of MAO gene, but evidence supporting these hypotheses is controversial. We aimed to investigate the mechanism of gene transcription regulator proteins on amphetamine-induced behavior. We applied aptamers containing a DNA binding sequence, as well as a random sequence (without target) to study the modulation of amphetamine-induced MAO levels and hyperactivity in living mice. METHODS: We pretreated in adult male C57black6 mice (Taconic Farm, Germantown, NY) (n >= 3 litters at a time), 2 to 3 months of age (23 +/- 2 gm body weight) with double stranded (ds) DNA aptamers with sequence specific to activator protein-1 (5ECdsAP1), nuclear factor-kappa beta (5ECdsNF-kB), special protein-1 (5ECdsSP-1) or cyclicAMP responsive element binding (5ECdsCreB) protein binding regions, 5ECdsRan [a random sequence without target], single-stranded AP-1 (5ECssAP-1) (8 nmol DNA per kg) or saline (5 MUl, intracerebroventricular [icv] injection) control before amphetamine administration (4 mg/kg, i.p.). We then measured and analyzed locomotor activities and the level of MAO-A and MAO-B activity. RESULTS: In the pathological condition of amphetamine exposure, we showed here that pretreatment with 5ECdsAP1 and 5ECdsNF-kB reversed the decrease of MAO-A activity (p < 0.05, t test), but not activity of the B isomer (MAO-B), in the ventral tegmental area (VTA) and substantia nigra (SN) of C57black6 mice. The change in MAO-A level coincided with a reversed amphetamine-induced restless behavior of mice. Pretreatments with saline, 5ECdsCreB, 5ECdsSP-1, 5ECdsRan or 5ECssAP-1 had no effect. CONCLUSION: Our data lead us to conclude that elevation of AP-1 or NF kB indirectly decreases MAO-A protein levels which, in turn, diminishes MAO-A ability in the VTA of the mesolimbic dopaminergic pathway that has been implicated in cells under stress especially in the SN and VTA. This study has implications for design for the treatment of drug exposure and perhaps Parkinson's dementia. PMID- 26841905 TI - The oral-systemic disease connection: a retrospective study. AB - OBJECTIVES: The study aimed at determining the association between oral disease and systemic health based on panoramic radiographs and general health of patients treated at Kuwait University Dental Center. The objective was to determine whether individuals exhibiting good oral health have lower propensity to systemic diseases. MATERIALS AND METHODS: A total of 1000 adult patients treated at Kuwait University Dental Center were randomly selected from the patient's records. The general health of patients was assessed from the medical history of each patient recorded during their visit to the clinic. The number of reported diseases and serious symptoms were used to develop a medical index. The oral health of these patients was assessed from panoramic radiographs to create an oral index by evaluating such parameters as caries, periodontitis, periapical lesions, pericoronitis, and tooth loss. RESULTS: In a total of 887 patients, 43.8 % had an oral index between 3 and 8, of which significantly higher (62.1 %) patients were with medical conditions compared to those without (33.2 %; p < 0.001). The Spearmans's correlation (rho') revealed a positive correlation (rho' = 0.360, p 0.001) between oral and medical index. Partial correlation, while controlling demographics, gender, nationality, and age, also showed a significant positive correlation (p < 0.001) between medical and oral index. CONCLUSIONS: The findings of this study showed a significant association between oral health and general health and confirmed the findings of previous reports as regards the existing correlation between dental infections and medical disorders. These results are not indicative of a causal relationship when the diagnosis of oral disease was based primarily on radiographic findings. Future research needs to include prospective clinical and interventional studies. CLINICAL RELEVANCE: The significance of the oral-systemic disease connection highlights the importance of preventing and treating oral disease which have profound medical implications on general health. PMID- 26841906 TI - Social world of organ transplantation, trafficking, and policies. AB - Although success of organ transplants reflects advances in medical procedures, the success has generated debates about the ethical standards and policies that govern transplants, especially the acquisition of organs for transplants. We focus on laws, policies, and organ trafficking to highlight the interdisciplinary perspectives that can shape our understanding of transplantation as a social phenomenon. We discuss international policies and country-specific legislation from Pakistan to point to gaps and their implications for protecting vulnerable people who are exploited for organ removal. International collaboration and the legal framework need to be strengthened to fight the menace globally and to deal with the cases of organ trafficking within the legal ambit of human trafficking so that the rights of victims are upheld by states, justice systems, and ultimately medical establishments and practitioners. PMID- 26841909 TI - Mechanistic insights into the recognition of 5-methylcytosine oxidation derivatives by the SUVH5 SRA domain. AB - 5-Methylcytosine (5 mC) is associated with epigenetic gene silencing in mammals and plants. 5 mC is consecutively oxidized to 5-hydroxymethylcytosine (5 hmC), 5 formylcytosine (5fC) and 5-carboxylcytosine (5caC) by ten-eleven translocation enzymes. We performed binding and structural studies to investigate the molecular basis of the recognition of the 5 mC oxidation derivatives in the context of a CG sequence by the SET- and RING-associated domain (SRA) of the SUVH5 protein (SUVH5 SRA). Using calorimetric measurements, we demonstrate that the SRA domain binds to the hydroxymethylated CG (5hmCG) DNA duplex in a similar manner to methylated CG (5mCG). Interestingly, the SUVH5 SRA domain exhibits weaker affinity towards carboxylated CG (5caCG) and formylated CG (5fCG). We report the 2.6 A resolution crystal structure of the SUVH5 SRA domain in a complex with fully hydroxymethyl CG and demonstrate a dual flip-out mechanism, whereby the symmetrical 5hmCs are simultaneously extruded from the partner strands of the DNA duplex and are positioned within the binding pockets of individual SRA domains. The hydroxyl group of 5hmC establishes both intra- and intermolecular interactions in the binding pocket. Collectively, we show that SUVH5 SRA recognizes 5hmC in a similar manner to 5 mC, but exhibits weaker affinity towards 5 hmC oxidation derivatives. PMID- 26841911 TI - Characteristics and critical success factors for implementing problem-based learning in a human resource-constrained country. AB - BACKGROUND: Problem-based learning (PBL) was introduced in Malawi in 2002 in order to improve the nursing education system and respond to the acute nursing human resources shortage. However, its implementation has been very slow throughout the country. OBJECTIVES: The objectives of the study were to explore and describe the goals that were identified by the college to facilitate the implementation of PBL, the resources of the organisation that facilitated the implementation of PBL, the factors related to sources of students that facilitated the implementation of PBL, and the influence of the external system of the organisation on facilitating the implementation of PBL, and to identify critical success factors that could guide the implementation of PBL in nursing education in Malawi. METHOD: This is an ethnographic, exploratory and descriptive qualitative case study. Purposive sampling was employed to select the nursing college, participants and documents for review.Three data collection methods, including semi-structured interviews, participant observation and document reviews, were used to collect data. The four steps of thematic analysis were used to analyse data from all three sources. RESULTS: Four themes and related subthemes emerged from the triangulated data sources. The first three themes and their subthemes are related to the characteristics related to successful implementation of PBL in a human resource-constrained nursing college, whilst the last theme is related to critical success factors that contribute to successful implementation of PBL in a human resource-constrained country like Malawi. CONCLUSION: This article shows that implementation of PBL is possible in a human resource-constrained country if there is political commitment and support. PMID- 26841910 TI - A Head-to-Head Comparison of the EQ-5D-5L and AQoL-8D Multi-Attribute Utility Instruments in Patients Who Have Previously Undergone Bariatric Surgery. AB - BACKGROUND: Psychosocial health status is an important and dynamic outcome for bariatric/metabolic surgery patients, as acknowledged in recent international standardised outcomes reporting guidelines. Multi-attribute utility-instruments (MAUIs) capture and assess an individual's health-related quality-of-life (HRQoL) within a single valuation, their utility. Neither MAUIs nor utilities were discussed in the guidelines. Many MAUIs (e.g. EQ-5D) target physical health. Not so the AQoL-8D. OBJECTIVES: Our objective was to explore agreement between, and suitability of, the EQ-5D-5L and AQoL-8D for assessing health state utility, and to determine whether either MAUI could be preferentially recommended for metabolic/bariatric surgery patients. METHODS: Utilities for post-surgical private-sector patients (n = 33) were assessed using both instruments and summary statistics expressed as mean [standard deviation (SD)] and median [interquartile range (IQR)]. Interchangeability of the MAUIs was assessed with Bland-Altman analysis. Discriminatory attributes were investigated through floor/ceiling effects and dimension-to-dimension comparisons. Spearman's rank measured associations between the instruments' utility values and with the body mass index (BMI). RESULTS: Mean (SD) EQ-5D-5L utility value was 0.84 (0.15) and median 0.84 (IQR 0.75-1.00). Mean (SD) AQoL-8D utility value was 0.76 (0.17) and median 0.81 (IQR 0.63-0.88). Spearman's rank was r = 0.68; (p < 0.001); however, Bland-Altman analysis revealed fundamental differences. Neither instrument gave rise to floor effects. A ceiling effect was observed with the EQ-5D-5L, with 36 % of participants obtaining a utility value of 1.00 (perfect health). These same participants obtained a mean utility of 0.87 on the AQoL-8D, primarily driven by the mental-super-dimension score (0.52). CONCLUSIONS: The AQoL-8D preferentially captures psychosocial aspects of metabolic/bariatric surgery patients' HRQoL. We recommend the AQoL-8D as a preferred MAUI for these patients given their complex physical/psychosocial needs. PMID- 26841912 TI - Factors contributing to late breast cancer presentation for health care amongst women in Kumasi, Ghana. AB - BACKGROUND: Delay in presenting breast cancer for health care is dangerous because it can increase the mortality rate amongst affected women. Delaying health care and treatment makes it difficult to manage advanced breast cancer successfully. Understanding the factors that contribute to delays in presentation for health care can save lives. OBJECTIVES: The purpose of the study was to describe the factors which contribute to the late presentation of Ghanaian women with breast cancer for health care at a tertiary hospital in Kumasi, Ghana. METHOD: A descriptive qualitative research design was utilised to answer the research question: 'What factors contribute to presenting with late breast cancer for health care amongst Ghanaian women who were treated for breast cancer at a tertiary hospital in Kumasi, Ghana?' A sample of 30 women diagnosed with breast cancer and presented with Stage II and Stage III participated in the study. Semi structured interviews and field notes were conducted for data collection. Content data analysis was used in line with the research question. FINDINGS: Five themes were discovered as findings. These were: lack of knowledge about breast cancer; fear of cancer treatment and its outcomes; poverty; traditional and spiritual beliefs and treatments and caring for others. CONCLUSIONS: We recommend the development of breast cancer awareness programmes and health education at primary health care level. PMID- 26841913 TI - Renal unit practitioners' knowledge, attitudes and practice regarding the safety of unfractionated heparin for chronic haemodialysis. AB - BACKGROUND: Chronic haemodialysis for adult patients with end-stage kidney failure requires a patent extracorporeal circuit, maintained by anticoagulants such as unfractionated heparin (UFH). Incorrect administration of UFH has safety implications for patients. OBJECTIVES: Firstly, to describe renal practitioners' self-reported knowledge, attitudes and practice (KAP) regarding the safe use of UFH and its effects; secondly, to determine an association between KAP and selected independent variables. METHOD: A cross-sectional descriptive survey by self-administered questionnaire and non-probability convenience sampling was conducted in two tertiary hospital dialysis units and five private dialysis units in 2013. RESULTS: The mean age of 74/77 respondents (96.1%), was 41.1 years. Most (41/77, 53.2%) had 0-5 years of renal experience. The odds of enrolled nurses having poorer knowledge of UFH than registered nurses were 18.7 times higher at a 95% Confidence Interval (CI) (1.9-187.4) and statistically significant (P = 0.013). The odds of delivering poor practice having <= five years of experience and no in-service education were 4.6 times higher at a 95% CI (1.4-15.6), than for respondents who had >= six years of experience (P = 0.014) and 4.3 times higher (95% CI 1.1-16.5) than for respondents who received in-service education (P = 0.032), the difference reaching statistical significance in both cases. CONCLUSION: Results suggest that the category of the professional influences knowledge and, thus, safe use of UFH, and that there is a direct relationship between years of experience and quality of haemodialysis practice and between having in-service education and quality of practice. PMID- 26841914 TI - Improving the quality of nurse clinical documentation for chronic patients at primary care clinics: A multifaceted intervention. AB - BACKGROUND: Deficiencies in record keeping practices have been reported at primary care level in the public health sector in South Africa. These deficiencies have the potential to negatively impact patient health outcomes as the break in information may hinder continuity of care. This disruption in information management has particular relevance for patients with chronic diseases. OBJECTIVES: The aim of this study was to establish if the implementation of a structured clinical record (SCR) as an adjunct tool to the algorithmic guidelines for chronic disease management improved the quality of clinical records at primary care level. METHOD: A quasi-experimental study (before and after study with a comparison group) was conducted across 30 primary health care clinics (PHCs) located in three districts in South Africa. Twenty PHCs that received the intervention were selected as intervention clinics and 10 facilities were selected as comparison facilities. The lot quality assurance sampling (LQAS) method was used to determine the number of records required to be reviewed per diagnostic condition per facility. RESULTS: There was a a statistically significant increase in the percentage of clinical records achieving compliance to the minimum criteria from the baseline to six months post intervention for both HIV patients on antiretroviral treatment and patients with non-communicable diseases (hypertension and diabetes). CONCLUSIONS: A multifaceted intervention using a SCR to supplement the educational outreach component (PC 101 training) has demonstrated the potential for improving the quality of clinical records for patients with chronic diseases at primary care clinics in South Africa. PMID- 26841915 TI - Persons living on a disability grant in Mpumalanga province: An insider perspective. AB - In Mpumalanga province, more than 45 000 persons with disability receive a disability grant. Although research regarding social grants in general and disability grants specifically had previously been conducted from various perspectives, none has been carried out in Mpumalanga and none to explore the impact of the disability grant on the lives of the recipients. The objective of the study was to gain an understanding of the impact of the disability grant on the lives of recipients living in Mpumalanga. The study was conducted as a contextual, exploratory and qualitative study. The target population was persons with a disability receiving a disability grant. Data gathering was conducted in October 2010 using a semi-structured interview technique. The data were analysed in terms of the social and economic impact of the disability grant in the life of the participant. A combination of three qualitative data analysis methods was used to analyse the data. The qualitative findings indicate that although it is an individual grant, the disability grant was used to support the whole family and was frequently the family's only income. Food, clothes and electricity was most frequently bought with the disability grant. Food often did not last for a month. The families were living precariously and any crisis, for example lapsing of the grant, would result in hunger and desperation as a result of their complete dependence on the disability grant.Without insight in how people live their lives, registered nurses may give health education to patients that they cannot implement, perpetuating the burden of disease in South Africa. PMID- 26841916 TI - Clinician perceptions and patient experiences of antiretroviral treatment integration in primary health care clinics, Tshwane, South Africa. AB - BACKGROUND: Primary Health Care (PHC) clinicians and patients are major role players in the South African antiretroviral treatment programme. Understanding their perceptions and experiences of integrated care and the management of people living with HIV and AIDS in PHC facilities is necessary for successful implementation and sustainability of integration. OBJECTIVE: This study explored clinician perceptions and patient experiences of integration of antiretroviral treatment in PHC clinics. METHOD: An exploratory, qualitative study was conducted in four city of Tshwane PHC facilities. Two urban and two rural facilities following different models of integration were included. A self-administered questionnaire with open-ended items was completed by 35 clinicians and four focus group interviews were conducted with HIV-positive patients. The data were coded and categories were grouped into sub-themes and themes. RESULTS: Workload, staff development and support for integration affected clinicians' performance and viewpoints. They perceived promotion of privacy, reduced discrimination and increased access to comprehensive care as benefits of service integration. Delays, poor patient care and patient dissatisfaction were viewed as negative aspects of integration. In three facilities patients were satisfied with integration or semi-integration and felt common queues prevented stigma and discrimination, whilst the reverse was true in the facility with separate services. Single-month issuance of antiretroviral drugs and clinic schedule organisation was viewed negatively, as well as poor staff attitudes, poor communication and long waiting times. CONCLUSION: Although a fully integrated service model is preferable, aspects that need further attention are management support from health authorities for health facilities, improved working conditions and appropriate staff development opportunities. PMID- 26841917 TI - Factors contributing to incivility amongst students at a South African nursing school. AB - BACKGROUND: This study determined the experiences of nurse educators of the factors contributing to the uncivil classroom behaviours of nursing students at a South African school of nursing. OBJECTIVE: To describe what nurse educators consider to be factors contributing to incivility among nursing students in a South African nursing school. METHOD: A qualitative descriptive design was used. Eleven nurse educators were purposively sampled for their experiences on the factors contributing to incivility. Individual face-to-face interviews were conducted until data saturation. RESULTS: The data analysed indicated that the educators had varying but often similar perspectives on which factors contribute to incivility among nursing students. The three themes that emerged from the data were academic, psycho-pathological and social factors.The themes were discussed on the basis of their reported impact on classroom behaviour and the implications for the teaching and learning environment. CONCLUSION: Conclusions were made that an educational screening system to identify committed students before admission into nursing education should be explored; that a support system should be explored for nurse educators to deal with incidents of uncivil behaviour, perhaps within policy frameworks in the nursing institution; that emotional support should be provided for students who may be experiencing difficulties adjusting to the rigours of post-secondary education; and that a forum should be set up for nurse educators to compare notes and share ideas on what works best in reducing the incidence of uncivil behaviours in the classroom setting. PMID- 26841918 TI - The views of intensive care nurses regarding short-term deployment. AB - BACKGROUND: Short-term deployment of nurses is usually used within the hospital units in order to 'balance the numbers' or to cover the shortage of staff in the different units. Often nurses in the intensive care unit (ICU) are sent to go and assist in other units, where there is not enough nursing staff or when their own unit is not busy. OBJECTIVES: The objective of this study was to explore the views of the ICU nurses regarding short-term deployment to other units. METHOD: A qualitative design was used, following interpretivism. The study was conducted in the ICUs of two hospitals in Gauteng Province, South Africa. Data were collected through focus group interviews with a purposive sample of registered nurses working in the selected ICUs, transcribed verbatim and analysed using open coding. RESULTS: The participants shared a similar view that deployment to other units should be based on a formal agreement, with policies and procedures. Consultation and negotiation are recommended prior to deployment of staff. Management should recognise and acknowledge expertise of ICU nurses in their own speciality area. CONCLUSION: The findings call for redesign of a deployment policy that will suit nurses from the speciality areas such as ICU. PMID- 26841919 TI - Patient safety culture in a district hospital in South Africa: An issue of quality. AB - BACKGROUND: The Nursing Act 33 of 2005 holds nurse practitioners responsible for all acts and omissions in the delivery of quality patient care. But quality patient care is influenced by a number of factors beyond the control of nurse practitioners. Patient safety culture is one such factor and is seldom explored in hospitals in developing countries. This article describes the patient safety culture of a district hospital in South Africa. OBJECTIVES: The study identified and analysed the factors that influence the patient safety culture by using the Manchester Patient Safety Framework at the National District Hospital, Bloemfontein, Free State Province. METHOD: A descriptive cross-sectional study was conducted and included the total population of permanent staff; community service health professionals; temporarily employed health professionals and volunteers. The standard Manchester Patient Safety Framework questionnaire was distributed with a response rate of 61%. RESULTS: Less than half of the respondents (42.4%; n = 61) graded their units as acceptable. Several quality dimensions were statistically significant for the employment profile: overall commitment to quality (p = 0.001); investigating patient incidents (p = 0.031); organisational learning following incidents (p < 0.001); communication around safety issues (p = 0.001); and team working around safety issues (p = 0.005). These same quality dimensions were also statistically significant for the professional profiles. Medical doctors had negative perceptions of all the safety dimensions. CONCLUSION: The research measured and described patient safety culture (PSC) amongst the staff at the National District Hospital (NDH). This research has identified the perceived inadequacies with PSC and gives nurse managers a clear mandate to implement change to ensure a PSC that fosters quality patient care. PMID- 26841920 TI - A conceptual framework to facilitate the mental health of student nurses working with persons with intellectual disabilities. AB - BACKGROUND: Student nurses (SNs) experience emotional discomfort during placement in the clinical psychiatric learning environment. This may negatively influence their mental health. Limited support is available to assist both SNs working with persons with intellectual disabilities and nurse educators during clinical accompaniment. OBJECTIVES: This article aims to discuss the generation of this framework to enhance student support. METHOD: A theory-generative, qualitative, exploratory, descriptive, contextual design was utilised to develop the framework by applying four steps. In step 1 concept analysis identified the central concept through field work. Data were collected from 13 SNs purposively selected from a specific higher educational institution in Gauteng through two focus group interviews, reflective journals, a reflective letter, naive sketches, drawings and field notes and analysed with thematic coding. The central concept was identified from the results, supported by a literature review and defined by essential attributes. The central concept was classified through a survey list and demonstrated in a model case. In step 2 the central concepts were placed into relationships with each other. The conceptual framework was described and evaluated in step 3 and guidelines for implementation were described in step 4. The focus of this article will be on generating the conceptual framework. RESULTS: The central concept was 'the facilitation of engagement on a deeper emotional level of SNs'. The conceptual framework was described and evaluated. CONCLUSION: The conceptual framework can enhance the educational practices of nurse educators and can SN's practices of care for persons with intellectual disabilities. PMID- 26841921 TI - Work-family and family-work conflicts amongst African nurses caring for patients with AIDS. AB - BACKGROUND: South African nursing environments are marked by various incapacitating stressors. This study explores work-family (W-F) and family-work (F-W) conflicts as aspects of stress amongst nurses working with patients who have AIDS. OBJECTIVES: The study sought to determine the value of W-F and F-W conflicts as predictors of work and family satisfaction, as well as turnover intentions and the moderating role of supervisor and significant other support, amongst nurses caring for patients with AIDS in public hospitals within the Capricorn and Mopani districts, Limpopo Province. METHODS: The study used a cross sectional design, with data collected at one point only. Ninety-one nursing staff provided the data for the study by completing structured, self-administered surveys. Analysis involved computing correlations of all study variables. Thereafter, associated variables were used as predictors. In each predictive analysis, the nurses' stress served as a control variable, W-F and F-W conflicts were the independent variables and significant others and supervisor supports were moderators. Interaction terms were derived from independent and moderator variables. RESULTS: Although the findings of the study were not generally supportive of the hypotheses advanced, they nevertheless showed, amongst other findings, that F-W conflict predicted work satisfaction whilst W-F conflict predicted turnover intentions. Moreover, significant other support had a direct effect on family satisfaction whilst supervisor support moderated reports of W-F conflict and experiences of work satisfaction. CONCLUSIONS: The study showed that inter-role models that appear to be established in the context of developed societies require some further investigations in South Africa. PMID- 26841922 TI - Spirituality and spiritual care in in the context of nursing education in South Africa. AB - BACKGROUND: In order for nursing education to prepare nurses for holistic patient care, it is critical that educators become more aware of the religious and spiritual dimensions in patient care and be able to provide adequate knowledge and skills for nurses to offer spiritually-based care in an ethical way. Furthermore, spiritual care is an essential component in the nursing context, as nurses have to care for patients who may often turn to the spiritual dimension to cope and heal. These aspects are important issues to be considered in planning what should be taught as part of spiritual care. OBJECTIVES: This paper presents findings from a study on nursing practitioners' views on the role of spiritual care in nursing practice and whether current nursing education has integrated this dimension into teaching. METHOD: A descriptive survey using a cross sectional design with 385 nurses was conducted between December 2012 and February 2013. Participants were recruited through multistage random sampling. Data analysis was undertaken using SSPS 0.20. RESULTS: All the participants (n = 385) concurred that spiritual care was a salient component of holistic patient care. They however stated that the primary barriers to providing spiritual care related to uncertainty on how to provide this type of care, and a lack of educational preparedness for this role. CONCLUSION: The study found that nurses were very accepting of the need for spiritual care as part of their nursing role but that nursing education had not paid adequate attention to integrating this dimension into the nursing curriculum. PMID- 26841923 TI - Menstrual knowledge and practices of female adolescents in Vhembe district, Limpopo Province, South Africa. AB - BACKGROUND: Although sexual issues are openly discussed in the media, sexuality and reproductive functions are treated as taboo. Menstruation is a normal physiologic process, but carries various meanings within cultures and is rarely discussed amongst families and communities. PURPOSE: This study sought to assess the knowledge and practices of secondary school girls towards menstruation in the Thulamela municipality of Limpopo Province, South Africa. METHODS: A quantitative descriptive study design was used and respondents were selected by means of convenience sampling from a population of secondary school girls. The sample consisted of 273 secondary school girls doing Grades 10-12. A self-administered questionnaire was used to collect data, which was analysed by computing frequencies and percentages using the Statistical Package for Social Sciences (SPSS version 12). FINDINGS: The findings revealed that respondents experienced menarche at 13 years and that menstruation is a monthly bleeding (80%) that happens to every female; it is a sign of adulthood (91%). 15% reported that it is the removal of dirt from the stomach and abdomen, 67% indicated the source of menstruation being the uterus, 65% the vagina and 13% from the abdomen. 73% reported having fear and anxiety at the first experience of bleeding and that they could not maintain adequate hygienic practices due to a lack of privacy and sanitary towels. CONCLUSION: Interventions are needed to increase girls' opportunities to discuss menstruation and access information from adults including mothers, parents and guardians. School-based sexuality education should be comprehensive, begin early and be regularly repeated. PMID- 26841924 TI - Effects of prenatal childbirth education for partners of pregnant women on paternal postnatal mental health: a systematic review and meta-analysis protocol. AB - BACKGROUND: The prevalence of paternal depression in the postnatal period is estimated to be approximately 10 %. Effective partner education during pregnancy has the possibility to prevent postnatal mental health problems and support expectant fathers in their transition to parenthood. This paper describes the protocol of a systematic review that will investigate the effects of prenatal childbirth education for partners of pregnant women particularly on paternal postnatal mental health. METHODS/DESIGN: We will search the databases of MEDLINE, CINAHL, EMBASE, PsycINFO, ERIC, and CENTRAL, using related search terms such as "partners of pregnant women," "education," and "prenatal support." Searches will be limited to randomized trials. Two review authors will independently screen eligible studies and assess risk of bias. We will report structured summaries of the included studies and conduct meta-analysis. DISCUSSION: Postnatal mental health of fathers is reported to have various effects on the health of the whole family. Therefore, support for expectant fathers is an important issue in the maternal and perinatal health-care system. However, resources on prenatal childbirth education for partners of pregnant women remain limited. The results of this review will provide evidence for prenatal education programs for expectant fathers. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015017919. PMID- 26841925 TI - Preference and willingness to pay for traditional medicine services in rural ethnic minority community in Vietnam. AB - BACKGROUND: Traditional medicine (TM) still plays an important role in a number of health care systems around the world, especially across Asian and African countries. In Vietnam, however, little is known about preference for traditional medicine use. This study assessed the prevalence of use, preference, satisfaction, and willingness to pay for TM services amongst rural ethnic minority community. METHODS: A cross-sectional survey in three provinces in the North and South of Vietnam. RESULTS: The results showed a high level of satisfaction with TM services, with more than 90 % of respondents reporting improved health status given the use of TM. Indicators for preference of TM over modern medicine are a longer distance to health station; being in an ethnic minority; being female; and having had higher service satisfaction. Although we did not have a comparison group, the high level of satisfaction with TM services is likely the result of a project targeting community health workers and the public regarding TM education and access promotion. Indeed, the community health workers are credited with relaying the information about TM more than any other sources. This suggests the importance of community health workers and community health centers in the promotion of TM use. CONCLUSIONS: Ethnic minority people prefer the use of traditional medicine services that supports the expansion of national programs and promotion of traditional medications. PMID- 26841926 TI - Associations of microbiota and toll-like receptor signaling pathway in esophageal adenocarcinoma. AB - BACKGROUND: Toll-like receptors (TLRs) recognize known molecules from microbes and have an established role in tumorigenesis. Using a rat model of esophageal adenocarcinoma, and human clinical samples, we investigated genes central to TLR mediated signal transduction and characterized the esophageal microbiome across the spectrum of esophageal adenocarcinoma carcinogenesis. METHODS: We surgically induced bile/acid reflux in rats and their esophagi were harvested at 40 weeks post-surgery. Tissue samples from the model were selected for gene expression profiling. Additionally, for rat and human samples microbiome analysis was performed using PCR-ESI-MS-TOF technology with validation by fluorescence in situ hybridization. RESULTS: Gene expression results in the rat model indicated a significant upregulation of TLRs 1-3, 6, 7 and 9 in EAC compared to normal epithelium. PCR-ESI-MS-TOF analysis revealed a prevalence of Escherichia coli in Barrett's esophagus (60%) and esophageal adenocarcinoma (100%), which was validated by fluorescence in situ hybridization. In the human clinical samples, Streptococcus pneumonia was detected in high abundance in gastroesophageal reflux disease and Barrett's esophagus (50-70%) in comparison to tumor adjacent normal epithelium, dysplasia, and esophageal adenocarcinoma (20-30%). E. coli was detected in the Barrett's esophagus and esophageal adenocarcinoma groups but was absent in the tumor adjacent normal epithelium, dysplasia, and the gastroesophageal reflux disease groups. CONCLUSIONS: We demonstrated an association between the TLR signaling pathway and E. coli hinting towards possible early molecular changes being mediated by microbes in the rat model of esophageal adenocarcinoma carcinogenesis. Studies on human clinical samples also corroborate results to some extent; however, a study with larger sample size is needed to further explore this association. PMID- 26841928 TI - The Sound Access Parent Outcomes Instrument (SAPOI): Construction of a new instrument for children with severe multiple disabilities who use cochlear implants or hearing aids. AB - OBJECTIVE: To report on the Phase 2 development of the Sound Access Parent Outcomes Instrument (SAPOI), a new instrument focused on formalizing outcomes that parents of children with severe multiple disabilities (SMD) who use amplification prioritize as important. METHODS: Phase 2 of this project involved item selection and refinement of the SAPOI based on (a) Phase 1 study participant input, (b) clinical specialist feedback, and (c) test-retest instrument reliability. Phase 1 participant responses were utilized to construct a draft version of the SAPOI. Next, clinical specialists examined the instrument for content validity and utility and instrument reliability was examined through a test-retest process with parents of children with SMD. RESULTS: The draft SAPOI was constructed based on Phase 1 participant input. Clinical specialists supported content validity and utility of the instrument and the inclusion of 19 additional items across four categories, namely Child Affect, Child Interaction, Parent Well-being, and Child's Device Use. The SAPOI was completed twice at one month intervals by parents of children with SMD to examine instrument reliability across the four categories (Child Affect, Child Interaction, Parent Well-being, and Child's Device Use). Instrument reliability was strong-to-excellent across all four sections. DISCUSSION: The SAPOI shows promise as a much-needed addition to the assessment battery currently used for children with SMD who use cochlear implants and hearing aids. It provides valuable information regarding outcomes resulting from access to sound in this population that currently used assessments do not identify. PMID- 26841927 TI - An Australian longitudinal pilot study examining health determinants of cardiac outcomes 12 months post percutaneous coronary intervention. AB - BACKGROUND: Percutaneous coronary intervention (PCI) is a very common revascularisation procedure for coronary artery disease (CAD). The purpose of this study was to evaluate cardiac outcomes, health related quality of life (HRQoL), resilience and adherence behaviours in patients who have undergone a PCI at two time points (6 and 12 months) following their procedure. METHODS: A longitudinal pilot study was conducted to observe the cardiac outcomes across a cohort of patients who had undergone a percutaneous coronary intervention (PCI). Participants who had undergone PCI 6 months prior were invited. Those participants who met the inclusion criteria and provided consent then completed a telephone survey (time point 1). These participants were then contacted 6 months later (i.e. 12 months post-intervention, time point 2) and the measures were repeated. RESULTS: All patients (n = 51) were recorded as being alive at time point 1. The multiple model indicated that controlling for other factors, gender was significantly associated with a linear combination of outcome measures (p = 0.004). The effect was moderate in magnitude (partial-eta(2) = 0.303), where males performed significantly better than females 6 months after the PCI procedure physically and with mood. Follow-up univariate ANOVAs indicated that gender differences were grounded in the scale measuring depression (PHQ9) (p = 0.005) and the physical component score of the short form measuring HRQoL (SF12 PCS) (p = 0.003). Thirteen patients were lost to follow-up between time points 1 and 2. One patient was confirmed to have passed away. The pattern of correlations between outcome measures at time point 2 revealed statistically significant negative correlation between the PHQ instrument and the resilience scale (CD RISC) (r = -0.611; p < 0.001); and the physical component score of the SF-12 instrument (r = -0.437; p = 0.054). CONCLUSIONS: Men were performing better than women in the 6 months post-PCI, particularly in the areas of mood (depression) and physical health. This pilot results indicate gender-sensitive practices are recommended particularly up to 6 months post-PCI. Any gender differences observed at 6 month appear to disappear at 12 months post-PCI. Further research into the management of mood particularly for women post-PCI is warranted. A more detailed inquiry related to access/attendance to secondary prevention is also warranted. PMID- 26841929 TI - Sponges against miR-19 and miR-155 reactivate the p53-Socs1 axis in hematopoietic cancers. AB - Normal cell proliferation is controlled by a balance between signals that promote or halt cell proliferation. Micro RNAs are emerging as key elements in providing fine signal balance in different physiological situations. Here we report that STAT5 signaling induces the miRNAs miR-19 and miR-155, which potentially antagonize the tumor suppressor axis composed by the STAT5 target gene SOCS1 (suppressor of cytokine signaling-1) and its downstream effector p53. MiRNA sponges against miR-19 or miR-155 inhibit the functions of these miRNAs and potentiate the induction of SOCS1 and p53 in mouse leukemia cells and in human myeloma cells. Adding a catalytic RNA motif of the hammerhead type within miRNA sponges against miR-155 leads to decreased miR-155 levels and increased their ability of inhibiting cell growth and cell migration in myeloma cells. The results indicate that antagonizing miRNA activity can reactivate tumor suppressor pathways downstream cytokine stimulation in tumor cells. PMID- 26841931 TI - Intraguild predation and competition impacts on a subordinate predator. AB - Intraguild (IG) predation and interspecific competition may affect the settlement and success of species in their habitats. Using data on forest-dwelling hawks from Finland, we addressed the impact of an IG predator, the northern goshawk Accipiter gentilis (goshawk), on the breeding of an IG prey, the common buzzard Buteo buteo. We hypothesized that the subordinate common buzzard avoids breeding in the proximity of goshawks and that interspecific competitors, mainly Strix owls, may also disturb common buzzards by competing for nests and food. Our results show that common buzzards more frequently occupied territories with a low IG predation threat and with no interspecific competitors. We also observed that common buzzards avoided territories with high levels of grouse, the main food of goshawks, possibly due to a risk of IG predation since abundant grouse can attract goshawks. High levels of small rodents attracted interspecific competitors to common buzzard territories and created a situation where there was not only an abundance of food but also an abundance of competitors for the food. These results suggest interplay between top-down and bottom-up processes which influence the interactions between avian predator species. We conclude that the common buzzard needs to balance the risks of IG predation and interference competition with the availability of its own resources. The presence of other predators associated with high food levels may impede a subordinate predator taking full advantage of the available food. Based on our results, it appears that interspecific interactions with dominant predators have the potential to influence the distribution pattern of subordinate predators. PMID- 26841930 TI - Ledipasvir/sofosbuvir fixed-dose combination tablet in Taiwanese patients with chronic genotype 1 hepatitis C virus. AB - BACKGROUND AND AIM: Pegylated-interferon-alpha plus ribavirin is the current standard-of-care regimen for treating chronic hepatitis C virus (HCV) infection in Taiwan; however, interferon-based regimens can be poorly tolerated. The interferon-free, two-drug, fixed-dose combination tablet ledipasvir/sofosbuvir is approved in Europe, the USA, and Japan for treating chronic genotype 1 HCV infection. Little is known about its efficacy/safety in Taiwanese patients. METHODS: In this multicenter, open-label, phase 3b (NCT02021656) study, 85 Taiwanese patients (n = 42, treatment-naive; n = 43, treatment-experienced) with chronic genotype 1 HCV infection (+/-compensated cirrhosis) received 12 weeks of ledipasvir/sofosbuvir fixed-dose combination tablet. The primary efficacy end point was the proportion of patients with sustained virologic response 12 weeks after treatment discontinuation (SVR12). Safety and pharmacokinetic data were collected. RESULTS: The overall SVR12 rate was 98% (83/85), with 100% (42/42) and 95% (41/43) of treatment-naive and treatment-experienced patients, respectively, achieving SVR12. There were no on-treatment virologic failures. One patient relapsed after treatment discontinuation; one patient withdrew consent on day 2. The most common treatment-emergent adverse event (AE) was headache (14%, 12/85). There was one grade 3 AE (small cell lung cancer unrelated to ledipasvir/sofosbuvir), no grade 4 AEs, and four grade 3-4 laboratory abnormalities. Only the patient with small cell lung cancer prematurely discontinued treatment. Two patients reported three serious AEs; none was considered related to ledipasvir/sofosbuvir. CONCLUSIONS: Data from this phase 3b study suggest that 12 weeks of once-daily treatment with the interferon-free, ribavirin-free regimen ledipasvir/sofosbuvir is effective and well-tolerated in Taiwanese patients with chronic genotype 1 HCV infection, irrespective of treatment history. PMID- 26841932 TI - Rasch analysis holds no brief for the use of the Dermatology Life Quality Index (DLQI) in Chinese neurodermatitis patients. AB - BACKGROUND: The Dermatology Life Quality Index (DLQI) is the most widely used measure of health-related quality of life (HRQoL) associated with skin disease. Recently, the psychometric properties of the DLQI have caused some controversy because the instrument appears not to meet the requirements of modern test theory. The purpose of this study was to assess whether these psychometric issues also occur in Chinese patients with neurodermatitis. METHODS: One hundred fifty consecutive outpatients (83 males and 67 females) seeking treatment for neurodermatitis were assessed for eligibility for this prospective study between July 1, 2011 and September 30, 2011. The DLQI and a demographic questionnaire were completed. One female participant who incompletely answered the DLQI was excluded. Data were analyzed using the Rasch model in order to obtain meaningful scores for the DLQI. Scale assessment included analysis of rating scale function, item fit to the Rasch model, aspects of person-response validity, unidimensionality, person-separation reliability, and differential item function. RESULTS: The rating scale advanced monotonically for all items in the DLQI, but item 9 did not demonstrate acceptable goodness-of-fit (Infit MnSq values >1.3) to the Rasch model. The 10 items of the DLQI met the criteria for person-separation reliability (PSI = 2.38) and the first latent dimension (general QoL) accounted for 50.8 % of the variance; but the variance explained by the second dimension (7.1 %) exceeded the criterion of 5 %. There were also limitations related to person-response validity, because >= 5 % (18.1 %) of cases demonstrated unacceptable fit. There was no uniform differential item functioning. CONCLUSIONS: For neurodermatitis patients, the DLQI seems to have poor fit to the Rasch model; therefore, we recommend against using this instrument with neurodermatitis patients. PMID- 26841933 TI - Molecular genetic analysis in 14 Czech Kabuki syndrome patients is confirming the utility of phenotypic scoring. AB - Kabuki syndrome (KS) is a dominantly inherited disorder mainly due to de novo pathogenic variation in KMT2D or KDM6A genes. Initially, a representative cohort of 14 Czech cases with clinical features suggestive of KS was analyzed by experienced clinical geneticists in collaboration with other specialties, and observed disease features were evaluated according to the 'MLL2-Kabuki score' defined by Makrythanasis et al. Subsequently, the aforementioned genes were Sanger sequenced and copy number variation analysis was performed by MLPA, followed by genome-wide array CGH testing. Pathogenic variants in KMT2D resulting in protein truncation in 43% (6/14; of which 3 are novel) of all cases were detected, while analysis of KDM6A was negative. MLPA analysis was negative in all instances. One female patient bears a 6.6 Mb duplication of the Xp21.2-Xp21.3 region that is probably disease causing. Subjective KS phenotyping identified predictive clinical features associated with the presence of a pathogenic variant in KMT2D. We provide additional evidence that this scoring approach fosters prioritization of patients prior to KMT2D sequencing. We conclude that KMT2D sequencing followed by array CGH is a diagnostic strategy with the highest diagnostic yield. PMID- 26841934 TI - Structure of the poly-C9 component of the complement membrane attack complex. AB - The membrane attack complex (MAC)/perforin-like protein complement component 9 (C9) is the major component of the MAC, a multi-protein complex that forms pores in the membrane of target pathogens. In contrast to homologous proteins such as perforin and the cholesterol-dependent cytolysins (CDCs), all of which require the membrane for oligomerisation, C9 assembles directly onto the nascent MAC from solution. However, the molecular mechanism of MAC assembly remains to be understood. Here we present the 8 A cryo-EM structure of a soluble form of the poly-C9 component of the MAC. These data reveal a 22-fold symmetrical arrangement of C9 molecules that yield an 88-strand pore-forming beta-barrel. The N-terminal thrombospondin-1 (TSP1) domain forms an unexpectedly extensive part of the oligomerisation interface, thus likely facilitating solution-based assembly. These TSP1 interactions may also explain how additional C9 subunits can be recruited to the growing MAC subsequent to membrane insertion. PMID- 26841936 TI - Carney Complex with Multiple Cardiac Myxomas, Pigmented Nodular Adrenocortical Hyperplasia, Epithelioid Blue Nevus, and Multiple Calcified Lesions of the Testis: A Case Report. PMID- 26841935 TI - A novel micro-straw for cryopreservation of small number of human spermatozoon. AB - Cryopreservation of few spermatozoa is still a major challenge for male fertility preservation. This study reports use a new micro-straw (LSL straw) for freezing few spermatozoa for intracytoplasmic sperm injection (ICSI). Semen samples from 22 fertile donors were collected, and each semen sample was diluted and mixed with cryoprotectant in a ratio of 1:1, and then frozen using three different straws such as LSL straw (50-100 MUl), traditional 0.25 ml and 0.5 ml straws. For freezing, all straws were fumigated with liquid nitrogen, with temperature directly reducing to -130--140 degrees C. Sperm concentration, progressive motility, morphology, acrosome integrity, and DNA fragmentation index were evaluated before and after freezing. After freezing-thawing, LSL straw group had significantly higher percentage of sperm motility than traditional 0.25 ml and 0.5 ml straw groups (38.5% vs 27.4% and 25.6%, P < 0.003). Sperm motility and acrosomal integrity after freezing-thawing were significantly lower than that of before freezing. However, there was no significant difference in morphology, acrosome, and DNA integrity between the three types of straws (P > 0.05). As LSL straws were thinner and hold very small volume, the freezing rate of LSL straw was obviously faster than 0.25 ml straw and 0.5 ml straws. In conclusion, LSL micro-straws may be useful to store few motile spermatozoa with good recovery of motility for patients undergoing ICSI treatment. PMID- 26841937 TI - Erratum to: 'Phase II/III weekly nab-paclitaxel plus gemcitabine or carboplatin versus gemcitabine/carboplatin as first-line treatment of patients with metastatic triple-negative breast cancer (the tnAcity study): study protocol for a randomized controlled trial. PMID- 26841938 TI - Regiospecific Synthesis of Benzoxepines through Pd-Catalyzed Carbene Migratory Insertion and C-C Bond Cleavage. AB - A new method for the synthesis of benzoxepines via migratory insertion into a Pd carbene followed by C-C bond cleavage was developed. Various benzoxepines were constructed by the regioselective ring expansion concomitant with the introduction of an aryl group at their 5-position. PMID- 26841939 TI - A cross-linguistic study of the development of gesture and speech in Zulu and French oral narratives. AB - The present study reports on a developmental and cross-linguistic study of oral narratives produced by speakers of Zulu (a Bantu language) and French (a Romance language). Specifically, we focus on oral narrative performance as a bimodal (i.e., linguistic and gestural) behaviour during the late language acquisition phase. We analyzed seventy-two oral narratives produced by L1 Zulu and French adults and primary school children aged between five and ten years old. The data were all collected using a narrative retelling task. The results revealed a strong effect of age on discourse performance, confirming that narrative abilities improve with age, irrespective of language. However, the results also showed cross-linguistic differences. Zulu oral narratives were longer, more detailed, and accompanied by more co-speech gestures than the French narratives. The parallel effect of age and language on gestural behaviour is discussed and highlights the importance of studying oral narratives from a multimodal perspective within a cross-linguistic framework. PMID- 26841940 TI - Imaging of differentiated thyroid carcinoma: 124I-PET/MRI may not be superior to 124I-PET/CT. PMID- 26841942 TI - [Recommendations of the German Society of Anaesthesiology and Intensive Care Medicine on structured patient handover in the perioperative phase : SBAR concept]. AB - Teamwork in the operating room and in the intensive care unit necessitates clear and precise communication; however, interruptions in communication frequently occur, especially in the perioperative phase. Patient are particularly susceptible to deficits in communication due to higher stress peaks, simultaneous admission of several patients and concomitant treatment of emergency cases etc. The German Society of Anaesthesiology and Intensive Care Medicine (DGAI) therefore recommends the implementation of the so-called SBAR concept (S: "situation", B: "background", A: "assessment", R: "recommendation") for standardization of patient handover. This concept was originally developed for high-risk areas and organizations with the aim of guaranteeing a rapid, effective and consistent transfer of information. PMID- 26841941 TI - (18)F-fluoromisonidazole positron emission tomography can predict pathological necrosis of brain tumors. AB - PURPOSE: Tumor necrosis is one of the indicators of tumor aggressiveness. (18)F fluoromisonidazole (FMISO) is the most widely used positron emission tomography (PET) tracer to evaluate severe hypoxia in vivo. Because severe hypoxia causes necrosis, we hypothesized that intratumoral necrosis can be detected by FMISO PET in brain tumors regardless of their histopathology. We applied FMISO PET to various types of brain tumors before tumor resection and evaluated the correlation between histopathological necrosis and FMISO uptake. METHODS: This study included 59 brain tumor patients who underwent FMISO PET/computed tomography before any treatments. According to the pathological diagnosis, the brain tumors were divided into three groups: astrocytomas (group 1), neuroepithelial tumors except for astrocytomas (group 2), and others (group 3). Two experienced neuropathologists evaluated the presence of necrosis in consensus. FMISO uptake in the tumor was evaluated visually and semi quantitatively using the tumor-to-normal cerebellum ratio (TNR). RESULTS: In visual analyses, 26/27 cases in the FMISO-positive group presented with necrosis, whereas 28/32 cases in the FMISO-negative group did not show necrosis. Mean TNRs with and without necrosis were 3.49 +/- 0.97 and 1.43 +/- 0.42 (p < 0.00001) in group 1, 2.91 +/- 0.83 and 1.44 +/- 0.20 (p < 0.005) in group 2, and 2.63 +/- 1.16 and 1.35 +/- 0.23 (p < 0.05) in group 3, respectively. Using a cut-off value of TNR = 1.67, which was calculated by normal reference regions of interest, we could predict necrosis with sensitivity, specificity, and accuracy of 96.7, 93.1, and 94.9 %, respectively. CONCLUSIONS: FMISO uptake within the lesion indicated the presence of histological micro-necrosis. When we used a TNR of 1.67 as the cut-off value, intratumoral micro-necrosis was sufficiently predictable. Because the presence of necrosis implies a poor prognosis, our results suggest that FMISO PET could provide important information for treatment decisions or surgical strategies of any type of brain tumor. PMID- 26841943 TI - Serum uric acid and hyperuricemia in U.S. adolescents: 40-year trends. PMID- 26841944 TI - Longgu (Fossilia Ossis Mastodi) alters the profiles of organic and inorganic components in Keishikaryukotsuboreito. AB - Longgu (Fossilia Ossis Mastodi) is a non-botanical crude drug, defined as "the ossified bone of large mammal" in the Japanese Pharmacopoeia sixteenth edition (JP16). It is a non-reproducible drug and is now facing the threat of exhaustion. To solve this problem, we aimed to clarify the role of longgu in Kampo prescriptions, which has not yet been scientifically ascertained. In this study, we focused on decoction of Keishikaryukotsuboreito (KRB). The profile of inorganic and organic components in the extract was analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and gas chromatography flame ionization detection (GC/FID), respectively. Twenty-five elements were detected by ICP-MS in KRB and longgu-free KRB (KB) decoctions. However, 23 elements were detected in unadultrated longgu (R) decoctions, and their total amount was 30 times lower than those of the KRB and KB decoctions were. No organic compounds were detected in R decoctions by GC/FID, though many were detected in KRB and KB decoctions. KRB decoctions were distinguished from KB decoctions by multivariate analysis. The only difference in the crude drugs was the presence of longgu, and therefore the difference in the profiles was attributed to the effect of longgu. Longgu was submitted to terahertz (THz) wave spectrometry after the decocting process. The THz spectra indicated that longgu adsorbed compounds during the KRB decoction. These results suggested that longgu not only releases its components, but also adsorbs ingredients from other crude drugs during decoction. PMID- 26841945 TI - Grain-rich diets altered the colonic fermentation and mucosa-associated bacterial communities and induced mucosal injuries in goats. AB - Remarkably little information is available about the impact of high-grain (HG) feeding on colonic mucosa-associated bacteria and mucosal morphology. In the present study, 12 male goats were randomly assigned to either a hay diet (n = 6) or an HG diet (65% grain; n = 6) to characterise the changes in the composition of the bacterial community in colonic mucosa and the mucosal morphology of the colon. The results showed that HG feeding decreased the colonic pH and increased the concentrations of total short chain fatty acids and lipopolysaccharides in colonic digesta. The principal coordinate analysis results showed that the HG diet altered the colonic mucosal bacterial communities, with an increase in the abundance of genus Blautia and a decrease in the abundance of genera Bacillus, Enterococcus, and Lactococcus. The HG-fed goats showed sloughing of the surface layer epithelium, intercellular tight junction erosion, cell mitochondrial damage, and upregulation of the relative mRNA expression of IL-2 and IFN-gamma in colonic mucosa. Collectively, our data indicate that HG feeding induced changes in colonic mucosal morphology and cytokines expression that might be caused by excessive fermentation and dramatic shifts in the bacterial populations in the colon. PMID- 26841946 TI - Temporal epilepsy lesions may be detected by the voxel-based quantitative analysis of brain FDG-PET images using an original block-matching normalization software. AB - INTRODUCTION: Statistical parametric mapping (SPM) provides useful voxel-by-voxel analyses of brain images from (18)F-fluorodesoxyglucose positron emission tomography (FDG-PET) after an initial step of spatial normalization through an anatomical template model. In the setting of the preoperative workup of patients with temporal epilepsy, this study aimed at assessing a block-matching (BM) normalization method, where most transformations are computed through small blocks, a principle that minimizes artefacts and overcomes additional image filtering. METHODS: Brain FDG-PET images from 31 patients with well-characterised temporal lobe epilepsy and among whom 22 had common mesial temporal lobe epilepsy were retrospectively analysed using both BM and conventional SPM normalization methods and with PET images from age-adjusted controls. Different threshold p values corrected for cluster volume were considered (0.01, 0.005, and 0.001). RESULTS: The use of BM provided equivalent values to those of SPM with regard to the overall volumes of temporal and extra-temporal hypometabolism, as well as similar sensitivity for detecting the involved temporal lobe, reaching 87 and 94 % for SPM and BM, respectively, at a threshold p value of 0.01. However, the ability to more accurately localize brain lesions within the mesial portion of the temporal lobe was a little higher with BM than with SPM with respective sensitivities reaching 78 % for BM and 45 % for SPM (p < 0.05). CONCLUSIONS: BM normalization compares well with conventional SPM for the voxel-based quantitative analysis of the FDG-PET images from temporal epilepsy patients. Further studies in different population are needed to determine whether BM is truly an accurate alternative to SPM in this setting. PMID- 26841948 TI - The Role of Professional Journals and Societies in the Future of a Field: A Reflection on the Partnership Between the American Journal of Epidemiology and the Society for Epidemiologic Research. AB - On this, the 100th anniversary of Johns Hopkins Bloomberg School of Public Health, we take the opportunity to reflect on the ties between the School, the American Journal of Epidemiology, and the Society for Epidemiologic Research. We discuss briefly the intersection of the School, the Journal, and the Society throughout their histories, with the aim of providing some insight into how the Journal and the Society have contributed to the evolution of the field. In so doing, we articulate the challenges that the Journal and the Society jointly face today, with an eye to finding opportunities in these challenges that can be helpful in coming decades. PMID- 26841947 TI - Comparison of the Efficacy of Atopalm((r)) Multi-Lamellar Emulsion Cream and Physiogel((r)) Intensive Cream in Improving Epidermal Permeability Barrier in Sensitive Skin. AB - INTRODUCTION: The management of sensitive skin, which affects over 60% of the general population, has been a long-standing challenge for both patients and clinicians. Because defective epidermal permeability barrier is one of the clinical features of sensitive skin, barrier-enhancing products could be an optimal regimen for sensitive skin. In the present study, we evaluated the efficacy and safety of two barrier-enhancing products, i.e., Atopalm ((r)) Multi Lamellar Emulsion (MLE) Cream and Physiogel ((r)) Intensive Cream for sensitive skin. METHODS: 60 patients with sensitive skin, aged 22-40 years old, were randomly assigned to one group treated with Atopalm MLE Cream, and another group treated with Physiogel Intensive Cream twice daily for 4 weeks. Lactic acid stinging test scores (LASTS), stratum hydration (SC) and transepidermal water loss (TEWL) were assessed before, 2 and 4 weeks after the treatment. RESULTS: Atopalm MLE Cream significantly lowered TEWL after 2 and 4 weeks of treatment (p < 0.01). In contrast, Physiogel Intensive Cream significantly increased TEWL after 2 weeks of treatment (p < 0.05) while TEWL significantly decreased after 4 week treatments. Moreover, both Atopalm MLE Cream and Physiogel Intensive Cream significantly increased SC hydration, and improved LASTS after 4 weeks of treatment. CONCLUSION: Both barrier-enhancing products are effective and safe for improving epidermal functions, including permeability barrier, SC hydration and LASTS, in sensitive skin. These products could be a valuable alternative for management of sensitive skin. FUNDING: Veterans Affairs Medical Center, San Francisco, California, USA, and NeoPharm Co., Ltd., Daejeon, Korea. PMID- 26841950 TI - A case of recurrent status epilepticus and successful management with progesterone. AB - Catamenial epilepsy (CE) is a commonly observed phenomenon among women with epilepsy, the management of which is both hormonal and non-hormonal. Progesterone therapy has been tried in these patients, as the possible mechanism of CE is withdrawal of progesterone and a higher oestrogen/progesterone ratio in the perimenstrual and periovulatory periods. Here, we describe a 24-year-old lady with multiple seizure types since childhood, which were refractory to adequate antiepileptic drug therapy after menarche with catamenial clustering of seizures. She went on to have several episodes of non-convulsive status epilepticus also with similar periodicity, which would abate only with midazolam infusion, without the need for ventilatory support. She was tried on acetazolamide, progesterone vaginal pessaries, and maximum tolerated doses of antiepileptic medications, but finally responded to intramuscular and oral progesterone, and has been seizure free for more than a year. PMID- 26841952 TI - Rebuttal from Raj K Goyal. PMID- 26841949 TI - The health system impact of false positive newborn screening results for medium chain acyl-CoA dehydrogenase deficiency: a cohort study. AB - BACKGROUND: There is no consensus in the literature regarding the impact of false positive newborn screening results on early health care utilization patterns. We evaluated the impact of false positive newborn screening results for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in a cohort of Ontario infants. METHODS: The cohort included all children who received newborn screening in Ontario between April 1, 2006 and March 31, 2010. Newborn screening and diagnostic confirmation results were linked to province-wide health care administrative datasets covering physician visits, emergency department visits, and inpatient hospitalizations, to determine health service utilization from April 1, 2006 through March 31, 2012. Incidence rate ratios (IRRs) were used to compare those with false positive results for MCADD to those with negative newborn screening results, stratified by age at service use. RESULTS: We identified 43 infants with a false positive newborn screening result for MCADD during the study period. These infants experienced significantly higher rates of physician visits (IRR: 1.42) and hospitalizations (IRR: 2.32) in the first year of life relative to a screen negative cohort in adjusted analyses. Differences in health services use were not observed after the first year of life. CONCLUSIONS: The higher use of some health services among false positive infants during the first year of life may be explained by a psychosocial impact of false positive results on parental perceptions of infant health, and/or by differences in underlying health status. Understanding the impact of false positive newborn screening results can help to inform newborn screening programs in designing support and education for families. This is particularly important as additional disorders are added to expanded screening panels, yielding important clinical benefits for affected children but also a higher frequency of false positive findings. PMID- 26841951 TI - Use of intravoxel incoherent motion MRI to assess renal fibrosis in a rat model of unilateral ureteral obstruction. AB - PURPOSE: To investigate the potential of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) in assessment of renal fibrosis using a rat model of unilateral ureteral obstruction (UUO). MATERIALS AND METHODS: Thirty-two UUO rats were created by complete ligation of the left ureter. IVIM was performed on a clinical 3.0T whole-body MRI scanner before the ligation (day 0) and on days 1, 3, 5, and 7 after ligation, and followed by histological analysis to examine alpha-smooth muscle actin (alpha-SMA) expression and tubulointerstitial lesion (TIL). IVIM parameters of renal cortex and medulla were measured. Changes in each parameter with time were analyzed and correlated with alpha-SMA expression level and grades of TIL. RESULTS: The apparent diffusion coefficient (ADC), true diffusion (D), and fractional perfusion (f) values between the cortex and inner medulla and between the cortex and outer medulla were found to be significantly different (P < 0.01). The average ADC, D, D*, and f values of renal cortex, outer medulla, and inner medulla on the UUO side significantly decreased over time (P < 0.05), and negatively correlated with both alpha-SMA expression level and TIL grades (Spearman Correlation Coefficient r: ADC and alpha-SMA.805, -0.707, 0.805; ADC and TIL: -0.758, -0.761, -0.810; D and alpha-SMA: -0.782, -0.486, 0.833; D and TIL: -0.518, -0.504, -0.826; D* and alpha-SMA: -0.707, -0.605, 0.639; D* and TIL: -0.450, -0.670, -0.701; f and alpha-SMA: -0.866, -0.872, 0.863; and TIL: -0.870, -0.875, -0.863). CONCLUSIONS: IVIM MRI shows great potential in noninvasive assessment of renal fibrosis induced by UUO. J. Magn. Reson. Imaging 2016;44:698-706. PMID- 26841953 TI - Review of 3-year outcomes of a very-low-energy diet-based outpatient obesity treatment programme. AB - Obesity is a complex disorder that requires a multidisciplinary treatment approach. This review evaluated 3-year outcomes of a very-low-energy diet (VLED) based programme at a tertiary hospital multidisciplinary weight management clinic. Medical records of all patients who agreed to undertake the VLED programme and who did not undergo bariatric surgery during the 3-year follow-up period were examined. Baseline data collection included demographic and anthropometric characteristics, childhood onset of obesity and co-existing medical conditions. Weight was modelled using a linear mixed effects analysis. Logistic regression analyses were used to model the probability of continuing to attend the clinic and to identify pre-treatment factors associated with longer duration of attendance. Data from 1109 patients were included. A total of 231 patients (19.2%) were still attending the clinic 3 years after their initial appointment. Mean weight loss among patients who attended the clinic for 3 years was 6.4 kg (3.5%, 95% confidence interval [CI] 2.8, 4.2%). People who were prescribed pharmacotherapy maintained greater weight loss at 3 years (7.7% vs. 2.3% without pharmacotherapy, 95% CI for difference 3.9, 7.0%). People who had an onset of obesity in childhood, who had co-existing hypertension or coronary artery disease, and who did not currently smoke were more likely to continue to attend the clinic for up to 3 years. In summary, in an outpatient weight management clinic, patients who undertook a VLED-based programme and continued in follow-up achieved a clinically significant weight loss at 3 years, particularly if pharmacotherapy was used for weight loss maintenance. PMID- 26841954 TI - Bioelectrical Signals and Ion Channels in the Modeling of Multicellular Patterns and Cancer Biophysics. AB - Bioelectrical signals and ion channels are central to spatial patterns in cell ensembles, a problem of fundamental interest in positional information and cancer processes. We propose a model for electrically connected cells based on simple biological concepts: i) the membrane potential of a single cell characterizes its electrical state; ii) the long-range electrical coupling of the multicellular ensemble is realized by a network of gap junction channels between neighboring cells; and iii) the spatial distribution of an external biochemical agent can modify the conductances of the ion channels in a cell membrane and the multicellular electrical state. We focus on electrical effects in small multicellular ensembles, ignoring slow diffusional processes. The spatio-temporal patterns obtained for the local map of cell electric potentials illustrate the normalization of regions with abnormal cell electrical states. The effects of intercellular coupling and blocking of specific channels on the electrical patterns are described. These patterns can regulate the electrically-induced redistribution of charged nanoparticles over small regions of a model tissue. The inclusion of bioelectrical signals provides new insights for the modeling of cancer biophysics because collective multicellular states show electrical coupling mechanisms that are not readily deduced from biochemical descriptions at the individual cell level. PMID- 26841955 TI - Versatile Types of MRI-Visible Cationic Nanoparticles Involving Pullulan Polysaccharides for Multifunctional Gene Carriers. AB - Owing to the low cytotoxicity and excellent biocompatibility, polysaccharides are good candidates for the development of promising biomaterials. In this paper, a series of magnetic resonance imaging (MRI)-visible cationic polymeric nanoparticles involving liver cell-targeting polysaccharides were flexibly designed for multifunctional gene delivery systems. The pullulan-based vector (PuPGEA) consisting of one liver cell-targeting pullulan backbone and ethanolamine-functionalized poly(glycidyl methacrylate) (denoted by BUCT-PGEA) side chains with abundant hydroxyl units and secondary amine was first prepared by atom transfer radical polymerization. The resultant cationic nanoparticles (PuPGEA-GdL or PuPGEA-GdW) with MRI functions were produced accordingly by assembling PuPGEA with aminophenylboronic acid-modified Gd-DTPA (GdL) or GdW10O36(9-) (GdW) via the corresponding etherification or electrostatic interaction. The properties of the PuPGEA-GdL and PuPGEA-GdW nanoparticles including pDNA condensation ability, cytotoxicity, gene transfection, cellular uptake, and in vitro and in vivo MRI were characterized in details. Such kinds of cationic nanoparticles exhibited good performances in gene transfection in liver cells. PuPGEA-GdW demonstrated much better MRI abilities. The present design of PuPGEA-based cationic nanoparticles with the liver cell-targeting polysaccharides and MRI contrast agents would shed light on the exploration of tumor-targetable multifunctional gene delivery systems. PMID- 26841957 TI - The evaluation of neural and vascular hyper-reactivity for sensitive skin. AB - BACKGROUND: The impaired barrier function has been studied comprehensively but few about the heighted neural and vascular reaction for the pathogenesis of sensitive skin. METHODS: Lactic acid stinging test (LAST) was used to identify sensitive subjects in selection phase. In the subsequent test phase, the baseline value of the blood flow (BF) and the current perception threshold (CPT) was measured by non-invasive instruments firstly. Then, the 0.001% capsaicin was applied to the nasolabial fold for 5 min. After the capsaicin test (CAT), the BF (immediately after the CAT) and CPT (1 h later after the CAT) were measured again. Blood sample were collected for genetic analysis of four TRPV1 gene single nucleotide polymorphisms between the positive-group and the negative-group. RESULT: The positive-group had lower baseline value of CPT at 5 and 250 Hz compared with the negative-group, but no difference in baseline value of BF. After the CAT, significant variation in CPT at 5 and 250 Hz values and the BF were found in positive-group but not in negative-group. The genotype frequencies of AG/GG in RS224534 and AC/CC in RS4790523 in positive-group were higher than that of negative-group. CONCLUSION: The sensitive subjects were prone to be stimulated by capsaicin to trigger neural and vascular hyper-reactivity. The genetic variation of TRPV1 and the unpleasant sensation demonstrate that TRPV1 play an important role in the pathogenesis of sensitive skin. Our study supports that sensory irritation inhibitors and anti-inflammatory compounds should be considered to be added in cosmetics to reduce the heighted neural and vascular reaction of sensitive skin. PMID- 26841958 TI - Statutory regulation needed to expose and stop medical fraud. PMID- 26841959 TI - Physiological significance of TRPV2 as a mechanosensor, thermosensor and lipid sensor. AB - This review provides a summary of the physiological significance of the TRPV2 ion channel. While TRPV2 was initially characterized as a noxious heat sensor, we found that TRPV2 can also act as a mechanosensor in embryonic neurons or adult myenteric neurons. Here, we summarize the newly characterized functions of TRPV2, including the research progress that has been made toward our understanding of TRPV2 physiology, and discuss other recent data pertaining to TRPV2. It is thought that TRPV2 may be an important drug target based on its broad expression patterns and important physiological roles. The possible associations between diseases and TRPV2 are also discussed. PMID- 26841961 TI - Stereoselective synthesis of 1,3-disubstituted isoindolines via Rh(III)-catalyzed tandem oxidative olefination-cyclization of 4-aryl cyclic sulfamidates. AB - Rh(III)-catalyzed tandem ortho C-H olefination of cyclic 4-aryl sulfamidates (1) and subsequent intramolecular cyclization are described. This reaction serves as a method for the direct and stereoselective synthesis of 1,3-disubstituted isoindolines (3) starting with enantiomerically enriched 4-aryl cyclic sulfamidates. In this process, the configurational integrity of the stereogenic center in the starting cyclic sulfamidate is completely retained. In addition, the process generates trans-1,3-disubstituted isoindolines exclusively. PMID- 26841960 TI - [Which drugs are useful during resuscitation? Which are not?]. AB - INTRODUCTION: Cardiopulmonary resuscitation represents a therapeutic challenge. Evidence-based guidelines, which were updated in 2015, give detailed advice on how to treat the patient. METHODS: Basic life support consists of cardiopulmonary resuscitation (30 chest compressions interrupted briefly to provide to 2 ventilations) and, if ventricular tachyarrhythmia is present, urgent cardiac defibrillation. Administration of drugs is one of the aspects of advanced life support. Vasopressors (adrenaline, vasopressin) aim to optimize coronary and cerebral perfusion. Antiarrhythmic drugs (amiodarone or lidocaine, when amiodarone is not available) are given during cardiac arrest to treat specific cardiac arrhythmias, mainly ventricular fibrillation and ventricular tachycardia. CONCLUSION: However, even in current guidelines, there is growing ambivalence towards drug treatment in the setting of cardiopulmonary resuscitation. This is mainly due to a paucity of robust clinical data. Most of the studies that have addressed the efficacy and safety of drugs during resuscitation are observational studies; however, a few small randomized controlled studies also exist. Recently, two large randomized controlled studies addressing the efficacy and safety of adrenaline versus placebo and amiodarone or lidocaine versus placebo have started. Both are currently recruiting patients. The hope is that the results of these studies will help to better define the role of drugs administered during cardiopulmonary resuscitation. PMID- 26841962 TI - On Visual Texture Preference: Can an Ecological Model Explain Why People Like Some Textures More Than Others? AB - What visual textures do people like and why? Here, we test whether the ecological valence theory proposed for color preferences can also predict people's preferences for visual texture. According to the theory, people should like visual textures associated with positive objects or entities and dislike visual textures associated with negative objects or entities. We compare the results for the ecological model with a more traditional texture-preference model based on computational features and find that the ecological model performs reasonably well considering its lower complexity, explaining 63% of the variance in the human preference data. PMID- 26841963 TI - Consent to treatment in the UK: time for practice to reflect the law. PMID- 26841965 TI - Assessment of left ventricular hemodynamic forces in healthy subjects and patients with dilated cardiomyopathy using 4D flow MRI. AB - We hypothesized that the direction of global left ventricular (LV) hemodynamic forces during diastolic filling are concordant with the main flow axes in normal LVs, but that this pattern would be altered in dilated and dysfunctional LVs. Therefore, we aimed to assess the LV hemodynamic filling forces in a group of healthy subjects and compare them to the results from a group of patients with dilated cardiomyopathy (DCM). Ten healthy subjects and 10 DCM patients were enrolled. Morphological short- (SAx) and long-axis (LAx) images and 4D flow MRI data were acquired at 1.5T. The LV pressure gradients were computed from the 4D flow data using the Navier-Stokes equations. By integrating the pressure gradients over the LV volume at each time frame, the magnitude and direction of the global hemodynamic force was calculated over the cardiac cycle. The hemodynamic forces acting in the SAx- and LAx-directions were used to calculate the "SAx-max/LAx-max"-ratio for the early (E-wave) and late (A-wave) diastolic filling. In the LAx-plane, the temporal progression of the hemodynamic force followed a consistent pattern in the healthy subjects. The "SAx-max/LAx-max" ratio was significantly larger at both E-wave (0.53 +/- 0.15 vs. 0.23 +/- 0.12, P < 0.0001) and A-wave (0.44 +/- 0.21 vs. 0.26 +/- 0.09, P < 0.03) in the DCM patients compared to the healthy subjects. 4D flow MRI data allow quantification of LV hemodynamic forces acting on the LV myocardial wall. The LV hemodynamic filling forces showed a similar temporal progression among healthy subjects, whereas DCM patients had forces that were more heterogeneous in their direction and magnitude during diastole. PMID- 26841964 TI - Current Approaches to the Treatment of Systemic-Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH). AB - Pulmonary arterial hypertension (PAH) is a severe condition causing significant morbidity and mortality in patients with systemic sclerosis (SSc). Despite the use of specific treatments, SSc-PAH survival remains poorer than in idiopathic PAH (IPAH). Recent therapeutic advances in PAH show a lower magnitude of response in SSc-PAH and a higher risk of adverse events, as compared to IPAH. The multifaceted underlying mechanisms and the multisystem nature of SSc probably explain part of the worse outcomes in SSc-PAH compared to IPAH. This review describes the current management of SSc-PAH with an emphasis on the impact of the different organ involvements in the prognosis and treatment response. An earlier detection of PAH and a better characterization of the clinical phenotypes of SSc PAH are warranted in clinical practice and future trials. Determinants of prognosis, surrogate markers of clinical improvement or worsening, and relevance of the common endpoints used in clinical trials should be evaluated in this specific population. A multidisciplinary approach in expert referral centers is mandatory for SSc-PAH management. PMID- 26841967 TI - Corrigendum: The effects of inhibitory control training for preschoolers on reasoning ability and neural activity. PMID- 26841966 TI - The effect of two glyphosate formulations on a small, diurnal lizard (Oligosoma polychroma). AB - Formulations of glyphosate-based herbicides continue to dominate the global herbicide market, while there continue to be concerns regarding the impact of this herbicide on non-target organisms. Research also indicates that the additives within certain glyphosate formulations, such as surfactants, are actually more toxic than the glyphosate active ingredient alone. Concerns arise in particular when glyphosate formulations are proposed for vegetation control in areas inhabited by rare or threatened species. Although the effect of glyphosate on birds and mammals is well studied, reptiles remain neglected in ecotoxicological studies. We investigated whether dermal exposure to two different commercial glyphosate formulations affected performance measures in the New Zealand common skink (Oligosoma polychroma). Fifty-eight skinks were each placed in a box of straw to simulate field conditions and sprayed once with Agpro Glyphosate 360, Yates Roundup Weedkiller (both at the label-specified concentrations of 144 mg glyphosate per 1 L water), or water (control). Agpro Glyphosate 360 contained ethoxylated tallow amine at a concentration of <200 g/L, while the surfactant within Yates Roundup Weedkiller was unknown. Following treatment skinks were kept in captivity and sampled for selected temperature and mass over a four-week period. Neither glyphosate formulation had a significant impact on mass. However, skinks treated with Yates Roundup Weedkiller selected significantly higher temperatures across 3 weeks following exposure. This heat seeking behaviour could be a fever response to increase metabolism and thereby counteract physiological stress. PMID- 26841968 TI - Exact quantum Bayesian rule for qubit measurements in circuit QED. AB - Developing efficient framework for quantum measurements is of essential importance to quantum science and technology. In this work, for the important superconducting circuit-QED setup, we present a rigorous and analytic solution for the effective quantum trajectory equation (QTE) after polaron transformation and converted to the form of Stratonovich calculus. We find that the solution is a generalization of the elegant quantum Bayesian approach developed in arXiv:1111.4016 by Korotokov and currently applied to circuit-QED measurements. The new result improves both the diagonal and off-diagonal elements of the qubit density matrix, via amending the distribution probabilities of the output currents and several important phase factors. Compared to numerical integration of the QTE, the resultant quantum Bayesian rule promises higher efficiency to update the measured state, and allows more efficient and analytical studies for some interesting problems such as quantum weak values, past quantum state, and quantum state smoothing. The method of this work opens also a new way to obtain quantum Bayesian formulas for other systems and in more complicated cases. PMID- 26841970 TI - Eicosyl ammoniums elicited thermal reduction alleyway towards gold nanoparticles and their chemo-sensor aptitude. AB - The construction of dimethylenebis(eicosyldimethylammonium bromide) surfactant directed gold nanoparticles (NPs) has been accomplished via a one-pot thermal reduction of HAuCl4 with trisodium citrate. The effect of cationic twin-tail surfactants, dimethylenebis(hexadecyldimethylammonium bromide) (16-2-16), dimethylenebis(octadecyldimethylammonium bromide) (18-2-18) and dimethylenebis(eicosyldimethylammonium bromide) (20-2-20), and their concentrations on shape and size of Au nanoparticles was thoroughly investigated. The UV-Vis spectroscopy and transmission electron microscopy (TEM) results show that longer tail length surfactants act as shape-directing agents promoting diversified morphologies. The formation of multiple-shaped Au nanoparticles, such as round, hexagonal, pentagonal, triangular and rod-like, has been confirmed from microstructure analysis; among them, many triangular shapes enhanced at elevated levels of surfactant concentration. In addition, the triangular Au nanoparticles with truncated corners were changed to smooth corners as the hydrocarbon chain length increased from (18-2-18) to (20-2-20). The concentration and hydrocarbon tails of twin-tail surfactants strongly influence the size and structure of Au NPs. In addition, the Au NPs synthesized with the twin-tail surfactant (18-2-18) were found to be highly sensitive towards Hg(2+), which could be because of the preferential adsorption of Hg(0) on the lower energy facets of triangular-shaped Au NPs. PMID- 26841969 TI - Mineral trioxide aggregate pulpotomy for permanent molars with clinical signs indicative of irreversible pulpitis: a preliminary study. AB - AIM: To prospectively investigate the clinical and radiographic success rates of pulpotomy in permanent molars with clinical signs and symptoms suggestive of irreversible pulpitis using mineral trioxide aggregate (MTA) as a pulp dressing agent. METHODOLOGY: Sixteen patients with 23 restorable permanent molars exhibiting signs and symptoms indicative of irreversible pulpitis were enrolled. A standardized operative procedure was followed for all participants. All teeth were isolated with a dental dam and caries was removed, and then, pulpotomy performed with a sterile round and/or flame shape diamond burs. Haemostasis was achieved with 5% sodium hypochlorite (NaOCl). A mixture of MTA was placed against the wound, and a moistened cotton pellet was placed over the MTA. Teeth were temporized with a glass-ionomer restoration. Three to ten days later, the interim restoration was removed and setting of MTA was evaluated. Teeth were restored with stainless steel crowns. Follow-up evaluations were scheduled at 3, 6, 12 months and annually thereafter. Descriptive statistics were used to assess outcomes. RESULTS: The age of patients at time of pulpotomy ranged between 7.6 and 13.6 years (mean = 10.7+/- 1.7 yrs). The majority of teeth (91%) had clinical signs and symptoms consistent with a diagnosis of symptomatic irreversible pulpitis and symptomatic apical periodontitis (78%). The follow-up examination period ranged from 18.9 to 73.6 months. Clinically and radiographically, all pulpotomies were considered successful at the end of the follow-up period. Radiographically, a hard tissue barrier was noticed in 13 (57%) teeth. CONCLUSION: In children, MTA was associated with high clinical and radiographic success as a pulpotomy agent in permanent teeth with clinical signs and symptoms suggestive of irreversible pulpitis. PMID- 26841972 TI - De novo steroid biosynthesis in human prostate cell lines and biopsies. AB - BACKGROUND: Intratumoral androgen formation may be a factor in the development of prostate cancer (PCa), particularly castration-resistant prostate cancer (CRPC). To evaluate the ability of the human prostate to synthesize de novo steroids, we examined the expression of key enzymes and proteins involved in steroid biosynthesis and metabolism. METHODS: Using TissueScanTM Cancer qPCR Arrays and quantitative RT-PCR, we performed comparative gene expression analyses between various prostate cell lines and biopsies, including normal, hyperplastic, cancerous, and androgen-deprived prostate cells lines, as well as normal, benign prostate hyperplasia (BPH), PCa, and CRPC human specimens. These studies were complemented with steroid biosynthesis studies in normal and BPH cells. RESULTS: Normal human prostate WPMY-1 and WPE1-NA22, benign prostate hyperplasia BPH-1, and cancer PC-3, LNCaP, and VCaP cell lines, as well as normal, BPH, PCa, and CRPC specimens, were used. Although all cell lines express mRNA encoding for hydroxymethylglutaryl-CoA reductase (HMGCR), the mitochondrial translocator protein TSPO and cholesterol side chain cleavage enzyme CYP11A1 were only observed in WPMY-1, BPH-1, and LNCaP cells. HSD3B1, HSD3B2, and CYP17A1 are involved in androgen formation and were not found in most cell lines. WPE1-NA22 and BPH-1 cells were unable to synthesize de novo steroids from mevalonate. Moreover, androgen-deprived cells did not have alterations in the expression of enzymes that could lead to de novo steroid formation. All prostate specimens expressed TSPO and CYP11A1. HSD3B1/2, CYP17A1, HSD17B5, and CYP19A1 mRNA expression was distinct to the profile observed in cells lines. The majority of BPH (90.9%) and PCa (83.1%) specimens contained CYP17A1, compared to control (normal) specimens (46.7%). BPH (82%), PCa (59%), normal (40%), and CRPC (34%) specimens expressed the four key enzymes that metabolize cholesterol to androgens. CONCLUSION: These studies question the use of prostate cell lines to study steroid biosynthesis and demonstrate that human prostate samples contain transcripts encoding for key steroidogenic enzymes and proteins indicating that they have the potential to synthesize de novo steroids. We propose CYP17A1 as a candidate enzyme that can be used for patient stratification and treatment in BPH and PCa. PMID- 26841971 TI - Probabilistic modelling of chromatin code landscape reveals functional diversity of enhancer-like chromatin states. AB - Interpreting the functional state of chromatin from the combinatorial binding patterns of chromatin factors, that is, the chromatin codes, is crucial for decoding the epigenetic state of the cell. Here we present a systematic map of Drosophila chromatin states derived from data-driven probabilistic modelling of dependencies between chromatin factors. Our model not only recapitulates enhancer like chromatin states as indicated by widely used enhancer marks but also divides these states into three functionally distinct groups, of which only one specific group possesses active enhancer activity. Moreover, we discover a strong association between one specific enhancer state and RNA Polymerase II pausing, linking transcription regulatory potential and chromatin organization. We also observe that with the exception of long-intron genes, chromatin state transition positions in transcriptionally active genes align with an absolute distance to their corresponding transcription start site, regardless of gene length. Using our method, we provide a resource that helps elucidate the functional and spatial organization of the chromatin code landscape. PMID- 26841973 TI - An intensified pi-hole in beryllium-doped boron nitride meshes: its determinant role in CO2 conversion into hydrocarbon fuels. AB - DFT investigations on beryllium-doped boron nitride meshes or sheets (BNs) predict the existence of a very reactive kind of novel material capable of spontaneously reducing the first hydrogenation step in the CO2 conversion mechanism. This impressive behaviour appears as a result of the very deep pi-hole generated by the beryllium moieties, and also determines its selectivity towards the production of CH4. PMID- 26841974 TI - Electrospun polystyrene nanofibers as a novel adsorbent to transfer an organic phase from an aqueous phase. AB - The aim of this work is to develop a simple phase-transfer method for dispersive liquid-liquid microextraction. For this purpose, a polystyrene nanofiber was prepared by a facile electrospinning strategy and used for the first time as an adsorbent to transfer the organic phase in dispersive liquid-liquid microextraction procedure. The fiber was characterized and its chemical stability and excellent hydrophobicity enable it to selectively adsorb the organic solvent in an aqueous sample. High porosity and specific surface area provide a large adsorption capacity. Under the optimal conditions, the developed dispersive liquid-liquid microextraction with high-performance liquid chromatography method was successfully applied to the analysis of aldehydes in environmental water samples. The merits of this approach are that it is easy-to-operate, low-cost, time-saving, and has satisfactory sensitivity. It provides an alternative way for fast and convenient phase transfer of the hydrophobic organic solvent from the aqueous phase. PMID- 26841975 TI - The encapsulated lithium effect on the first hyperpolarizability of C60Cl2 and C60F2. AB - In this paper, we report a study on the structure and first hyperpolarizability of C60Cl2 and C60F2. The calculation results show that the first hyperpolarizabilities of C60Cl2 and C60F2 were 172 au and 249 au, respectively. Compared with the fullerenes, the first hyperpolarizability of C60Cl2 increased from 0 au to 172 au, while the first hyperpolarizability of C60F2 increased from 0 au to 249 au. In order to further increase the first hyperpolarizability of C60Cl2 and C60F2, Li@C60Cl2 and Li@C60F2 were obtained by introducing a lithium atom to C60Cl2 and C60F2. The first hyperpolarizabilities of Li@C60Cl2 and Li@C60F2 were 2589 au and 985 au, representing a 15-fold and 3.9-fold increase, respectively, over those of C60Cl2 and C60F2. The transition energies of four molecules (C60Cl2, Li@C60Cl2, C60F2, Li@C60F2) were calculated, and were found to be 0.17866 au, 0.05229 au, 0.18385 au, and 0.05212 au, respectively. A two-level model explains why the first hyperpolarizability increases for Li@C60Cl2 and Li@C60F2. PMID- 26841977 TI - Do soybeans select specific species of Bradyrhizobium during growth? AB - Soybean is an important crop, with processed soybeans being the second largest source of vegetable oil and the largest source of animal protein feed in the world. Nodules on soybean roots are responsible for symbiotic nitrogen fixation, enabling soybean plants to obtain sufficient nitrogen for growth and seed production. Because nitrogen is an essential, but often limiting, nutrient for plant growth, improvements in nitrogen fixation are highly required in agriculture. We recently reported a comprehensive analysis of rhizosphere bacterial communities during soybean growth in a field in Kyoto prefecture, Japan. The bacterial communities of the rhizosphere changed significantly during growth, with potential plant growth-promoting rhizobacteria, including Bacillus, Bradyrhizobium, and Rhizobium, increasing in a stage-specific manner. In this addendum, we focus on changes in Bradyrhizobium during soybean growth, suggesting that soybean plants select for symbiotic partners. PMID- 26841976 TI - A two-layer ONIOM study of thiophene cracking catalyzed by proton- and cation exchanged FAU zeolite. AB - A two-layer ONIOM study on the hydrodesulfurization mechanism of thiophene in H FAU and M-FAU (M = Li(+), Na(+), and K(+)) has been carried out. The calculated results reveal that in H-FAU, for a unimolecular mechanism, the rate-determining step is hydrogenation of alkoxide intermediate. The assistance of H2O and H2S molecules does not reduce the difficulty of the C-S bond cracking step more effectively. A bimolecular hydrodesulfurization mechanism is more favorable due to the lower activation barriers. The rate-determining step is the formation of 2 methylthiophene, not the C-S bond cracking of thiophene. Moreover, the ring opening of thiophene is much easier to occur than the desulfurization step. A careful analysis of energetics indicates that H2S, propene, and methyl thiophene are the major products for the hydrodesulfurization process of thiophene over H FAU zeolite, in good agreement with experimental findings. In M-FAU zeolites, both unimolecular and bimolecular cracking processes are difficult to occur because of the high energy barriers. Compared to the case on H-FAU, the metal cations on M-FAU increase the difficulty of occurrence of bimolecular polymerization and subsequent C-S bond cracking steps. Graphical abstract Hydrodesulfurization process of thiophene can take place in H-FAU zeolite. Two different mechanisms, unimolecular and bimolecular ones, have been proposed and evaluated in detail. The bimolecular mechanism is more favorable due to lower activation barrier as described in the picture above. Our calculated data indicate that H2S, propene, and methylthiophene are the major products, in good agreement with experimental observations. The effect of metal cations on the reaction mechanism is also investigated in this work. PMID- 26841978 TI - Meeting the unique health-care needs of LGBTQ people. PMID- 26841979 TI - Zika virus: a new global threat for 2016. PMID- 26841980 TI - India's air pollution: a new government and global plan. PMID- 26841981 TI - Civil-military cooperation in Ebola and beyond. PMID- 26841983 TI - WHO puts healthy ageing on the front burner. PMID- 26841984 TI - Will Nigeria's new government fix the health system? PMID- 26841985 TI - Blood bottles. PMID- 26841988 TI - Samson Kinyanjui: pressing for more science in Africa, by Africans. PMID- 26841989 TI - Antibiotic antagonist: the curious career of Rene Dubos. PMID- 26841990 TI - Henry Krum. PMID- 26841991 TI - Systematic reviews and research waste. PMID- 26841992 TI - Systematic reviews and research waste. PMID- 26841993 TI - Oseltamivir for influenza. PMID- 26841994 TI - Systematic reviews and research waste. PMID- 26841995 TI - Perinatal depressive symptoms preceded by mental health problems. PMID- 26841996 TI - Oseltamivir for influenza - Authors' reply. PMID- 26841998 TI - Perinatal depressive symptoms preceded by mental health problems - Authors' reply. PMID- 26842002 TI - The emerging view of Firmicutes as key fibre degraders in the human gut. PMID- 26842005 TI - Impact of brief self-affirmation manipulations on university students' reactions to risk information about binge drinking. AB - OBJECTIVES: Binge drinking is associated with an array of negative health consequences and is particularly prevalent in university students. Health-risk messages about alcohol may fail to change such behaviour because they are dismissed or derogated. The present study sought to compare the effect of three brief self-affirmation manipulations on message processing, message acceptance, and subsequent alcohol-related behaviour in university students. DESIGN: Participants (N = 307) were randomly allocated to condition (kindness questionnaire, values essay, attributes questionnaire, control questionnaire) before reading a health-risk message about binge drinking. METHODS: After reading the message, participants completed measures of message processing (message reactance, message evaluation, counter-arguing) and message acceptance (perceived risk, intention, plans) as well as a manipulation check. Alcohol consumption was assessed 1 week later. RESULTS: Participants in all three self-affirmation conditions scored significantly higher than participants in the control condition on the manipulation check measure. All other self-affirmation effects were non significant. CONCLUSIONS: While the three self-affirmation manipulations were found to be self-affirming, they failed to impact on measures of message processing, message acceptance, or subsequent behaviour. The findings concur with previous research that questions the use of self-affirmation to reduce alcohol consumption in university students. Current self-affirmation manipulations may not be strong enough to overcome defensive processing of health-risk messages about alcohol in students and/or prime social goals that are related to the domain under threat (i.e., alcohol consumption), thereby nullifying any positive self-affirmation effects. Statement of contribution What is already known on this subject? Health-risk messages to reduce alcohol consumption (e.g., binge drinking) in university students may fail due to defensive processing (e.g., message derogation). Self-affirmation has been proposed as a technique to bolster one's self-integrity and promote open-minded processing of health-risk messages. Most previous studies that have presented health-risk messages about alcohol to university students have used a values essay to self-affirm participants with equivocal results. What does this study add? There are few studies that have directly compared different self-affirmation manipulations. All three self affirmation manipulations were found by participants to be self-affirming, consistent with the idea that there are multiple ways individuals can self affirm, but had no significant effects on message processing, message acceptance, or behaviour. Self-affirmation manipulations may lead individuals to reflect on interpersonal values that are related to alcohol consumption in students and may therefore prime the very cognitions and behaviour that they seek to reduce. PMID- 26842001 TI - Fanconi anemia genes in lung adenocarcinoma- a pathway-wide study on cancer susceptibility. AB - BACKGROUND: Carcinogens in cigarette smoke can induce the formation of DNA-DNA cross-links, which are repaired by the Fanconi anemia (FA) pathway, and it is tempting to speculate that this pathway is involved in lung tumorigenesis. This study is to determine whether genetic polymorphism of the FA genes is associated with an elevated risk of lung adenocarcinoma, and whether the association between genotypes and risk is modified by exposure to cigarette smoke. METHODS: This case control study genotyped 53 single-nucleotide polymorphisms (SNPs) in FA genes in 709 patients (354 males and 355 females) with lung adenocarcinoma and in 726 cancer-free individuals (339 males and 387 females). Genotypic frequencies of SNPs were compared between cases and controls to identify important FA genes associated with cancer susceptibility. Joint effects in determining cancer risk contributed by genes and smoking-related risk factors and by multiple genes involved in different FA subpathways were evaluated by multivariate regression analysis and stratified analysis. All analyses were performed on males and females separately, and the comparison of results was considered a way of examining the validity of study findings. RESULTS: Lung adenocarcinomas in both male and female patients were associated with (a) genotypic polymorphisms of FANCC and FANCD1; (b) a combined effect of harboring a higher number of high-risk genotypes and smoking/passive smoking; (c) specific interactions of multiple genes, proteins encoded by which have been known to work jointly within the FA pathway. CONCLUSIONS: Genetic polymorphism of the FA genes is associated with inter-individual susceptibility to lung adenocarcinoma. PMID- 26842007 TI - Tetrahedral M(II) based binuclear double-stranded helicates: single-ion-magnet and fluorescence behaviour. AB - A rare class of dinuclear double-stranded helicates having tetrahedral metal centres with formulae [Co2(L(1))2].2(CH3CN) (1), [Co2(L(2))2].6(CH3CN) (2), [Zn2(L(1))2].2(CH3CN).(CH3OH) (3) and [Zn2(L(2))2].4(CH3CN) (4) were synthesized and characterized. Detailed dc and ac magnetic susceptibility measurements reveal the presence of field induced slow magnetic relaxation behaviour in high spin tetrahedral Co(II) centres with an easy-plane magnetic anisotropy. Complexes 1 and 2 are the rare examples of transition metal based helicates showing such behaviour. Furthermore, 3 and 4 exhibit fluorescence emission in different solvents that are analyzed in terms of fluorescence quantum yields and lifetimes. PMID- 26842006 TI - Identification of avian leukosis virus subgroup J-associated acutely transforming viruses carrying the v-src oncogene in layer chickens. AB - To elucidate the molecular basis for the rapid oncogenicity of an acutely transforming avian leukosis virus (ALV), isolated from fibrosarcomas in Hy-Line Brown commercial layer chickens infected with ALV subgroup J (ALV-J), the complete genomic structure of the provirus was determined. In addition to ALV-J replication-complete virus SDAU1102, five proviral DNA genomes, named SJ-1, SJ-2, SJ-3, SJ-4 and SJ-5, carrying different lengths of the v-src oncogene were amplified from original tumours and chicken embryo fibroblasts (CEFs) infected with viral stocks. The genomic sequences of the SJ-1-SJ-5 provirus were closely related to that of SDAU1102 but were defective. The results of Western blot analysis and immunohistochemical staining also showed overexpression of the p60v src protein in infected CEFs and tumour tissue. To the best of our knowledge, this is the first report of the isolation and identification of acutely transforming viruses carrying the v-src oncogene with ALV-J as the helper virus. It also offers insight into the generation of acutely transforming ALVs carrying the v-src oncogene. PMID- 26842008 TI - Anterior Mediastinal Mass. PMID- 26842009 TI - One Effect Size Does Not Fit All--Is the Depression-Inflammation Link Missing in Racial/Ethnic Minority Individuals? PMID- 26842010 TI - Binding of imidacloprid, thiamethoxam and N-desmethylthiamethoxam to nicotinic receptors of Myzus persicae: pharmacological profiling using neonicotinoids, natural agonists and antagonists. AB - BACKGROUND: The increasing structural diversity of the neonicotinoid class of insecticides presently used in crop protection calls for a more detailed analysis of their mode of action at their cellular targets, the nicotinic acetylcholine receptors. RESULTS: Comparative radioligand binding studies using membranes of Myzus persicae (Sulzer) and representatives of the chloropyridyl subclass (imidacloprid), the chlorothiazolyl subclass (thiamethoxam), the tetrahydrofuranyl subclass (dinotefuran), as well as the novel sulfoximine type (sulfoxaflor), which is not a neonicotinoid, reveal significant differences in the number of binding sites, the displacing potencies and the mode of binding interference. Furthermore, the mode of interaction of [3 H]thiamethoxam and the nicotinic antagonists methyllycaconitine and dihydro-beta-erythroidine is unique, with Hill values of >1, clearly different to the values of around unity for [3 H]imidacloprid and [3 H]N-desmethylthiamethoxam. The interaction of [3 H]N desmethylthiamethoxam with the agonist (-)nicotine is also characterised by a Hill value of >1. CONCLUSIONS: There is no single conserved site or mode of binding of neonicotinoids and related nicotinic ligands to their target receptor, but a variety of binding pockets depending on the combination of receptor subunits, the receptor subtype, its functional state, as well as the structural flexibility of both the binding pockets and the ligands. (c) 2016 Society of Chemical Industry. PMID- 26842012 TI - Modulation of auditory spatial attention by visual emotional cues: differential effects of attentional engagement and disengagement for pleasant and unpleasant cues. AB - Previous research has demonstrated that threatening, compared to neutral pictures, can bias attention towards non-emotional auditory targets. Here we investigated which subcomponents of attention contributed to the influence of emotional visual stimuli on auditory spatial attention. Participants indicated the location of an auditory target, after brief (250 ms) presentation of a spatially non-predictive peripheral visual cue. Responses to targets were faster at the location of the preceding visual cue, compared to at the opposite location (cue validity effect). The cue validity effect was larger for targets following pleasant and unpleasant cues compared to neutral cues, for right-sided targets. For unpleasant cues, the crossmodal cue validity effect was driven by delayed attentional disengagement, and for pleasant cues, it was driven by enhanced engagement. We conclude that both pleasant and unpleasant visual cues influence the distribution of attention across modalities and that the associated attentional mechanisms depend on the valence of the visual cue. PMID- 26842014 TI - Linking Competency with Training Needs: Session Summary on Disaster Studies and Evaluation, Session BO-17. AB - This section of Prehospital and Disaster Medicine (PDM) presents reports and summaries of the 19th World Congress on Disaster and Emergency Medicine (WCDEM) held in Cape Town, South Africa in April of 2015. Abstracts of Congress oral and poster presentations were published in April 2015 as a supplement to PDM (Volume 30, Supplement 1). Reports and session summaries of the 19th World Congress on Disaster and Emergency Medicine. PMID- 26842013 TI - Increased Expression of Transient Receptor Potential Vanilloid 4 in Cortical Lesions of Patients with Focal Cortical Dysplasia. AB - AIM: Focal cortical dysplasia (FCD) represents a well-known cause of medically intractable epilepsy. Studies found that transient receptor potential vanilloid receptor 4 (TRPV4) may participate in the occurrence of seizures. This study investigated the expression patterns of TRPV4 in FCD and the cascade that regulate functional state of TRPV4 in cortical neurons. METHODS: Thirty-nine surgical specimens from FCD patients and 10 age-matched control samples from autopsies were included in this study. Protein expression and distribution were detected by Western blot, immunohistochemistry, and immunofluorescence staining. Calcium imaging was used to detect the TRPV4-mediated Ca(2+) influx in cortical neurons. RESULTS: (1) The protein levels of TRPV4 and of an upstream factor, protein kinase C (PKC), were markedly elevated in FCD. (2) TRPV4 staining was stronger in the dysplastic cortices of FCD and mainly observed in neuronal microcolumns and malformed cells. (3) The activation of TRPV4 was central for [Ca(2+)]i elevation in cortical neurons, and this activity of TRPV4 in cortical neurons was regulated by the PKC, but not the PKA, pathway. CONCLUSION: The overexpression and altered cellular distribution of TRPV4 in FCD suggest that TRPV4 may potentially contribute to the epileptogenesis of FCD. PMID- 26842015 TI - A Sheet-like Carbon Matrix Hosted Sulfur as Cathode for High-performance Lithium Sulfur Batteries. AB - Lithium-sulfur (Li-S) batteries are a promising candidate of next generation energy storage systems owing to its high theoretical capacity and energy density. However, to date, its commercial application was hindered by the inherent problems of sulfur cathode. Additionally, with the rapid decline of non-renewable resources and active appeal of green chemistry, the intensive research of new electrode materials was conducted worldwide. We have obtained a sheet-like carbon material (shaddock peel carbon sheets SPCS) from organic waste shaddock peel, which can be used as the conductive carbon matrix for sulfur-based cathodes. Furthermore, the raw materials are low-cost, truly green and recyclable. As a result, the sulfur cathode made with SPCS (SPCS-S), can deliver a high reversible capacity of 722.5 mAh g(-1) at 0.2 C after 100 cycles with capacity recuperability of ~90%, demonstrating that the SPCS-S hybrid is of great potential as the cathode for rechargeable Li-S batteries. The high electrochemical performance of SPCS-S hybrid could be attributed to the sheet like carbon network with large surface area and high conductivity of the SPCS, in which the carbon sheets enable the uniform distribution of sulfur, better ability to trap the soluble polysulfides and accommodate volume expansion/shrinkage of sulfur during repeated charge/discharge cycles. PMID- 26842016 TI - Evidence-Based Decision Making When Designing Environments for Physical Activity: The Role of Public Health. AB - The important role that the environment plays in health and well-being is widely accepted, as is the impact that the built and natural environment can have on levels of physical activity. As levels of physical activity are a key determinant of health, promoting physical activity through actions to improve the environment is a priority for public health action. The challenge for public health is to ensure that the way the environment is shaped and transformed by a range of professionals, organisations and agencies, maximises health gain in relation to health, including physical activity. This article discusses how the public health profession can and should contribute to generating and disseminating evidence to inform decision-making processes for designing environments to promote physical activity. There are significant challenges to building and applying the evidence base in this area. These include the complex environments in which interventions operate, disciplinary differences in approaches to evidence generation and use, and the fact that public health has little responsibility for environmental change. However, case studies of best practice, presented in the article, offer a snapshot of how challenges can be overcome, to build an accessible evidence base and help to improve the environment for the promotion of physical activity. PMID- 26842019 TI - Better together. PMID- 26842018 TI - The next steps on Zika. PMID- 26842020 TI - Green growth. PMID- 26842021 TI - Make journals report clinical trials properly. PMID- 26842017 TI - The Great British Medalists Project: A Review of Current Knowledge on the Development of the World's Best Sporting Talent. AB - The literature base regarding the development of sporting talent is extensive, and includes empirical articles, reviews, position papers, academic books, governing body documents, popular books, unpublished theses and anecdotal evidence, and contains numerous models of talent development. With such a varied body of work, the task for researchers, practitioners and policy makers of generating a clear understanding of what is known and what is thought to be true regarding the development of sporting talent is particularly challenging. Drawing on a wide array of expertise, we address this challenge by avoiding adherence to any specific model or area and by providing a reasoned review across three key overarching topics: (a) the performer; (b) the environment; and (c) practice and training. Within each topic sub-section, we review and calibrate evidence by performance level of the samples. We then conclude each sub-section with a brief summary, a rating of the quality of evidence, a recommendation for practice and suggestions for future research. These serve to highlight both our current level of understanding and our level of confidence in providing practice recommendations, but also point to a need for future studies that could offer evidence regarding the complex interactions that almost certainly exist across domains. PMID- 26842033 TI - Zika virus: Brazil's surge in small-headed babies questioned by report. PMID- 26842034 TI - Academics across Europe join 'Brexit' debate. PMID- 26842035 TI - University seeks private donations to offset climate funding crunch. PMID- 26842036 TI - Drugmakers target depression's cognitive fog. PMID- 26842038 TI - Germany's science hubs win in major research revamp. PMID- 26842037 TI - UK scientists gain licence to edit genes in human embryos. PMID- 26842039 TI - The mystery of the expanding tropics. PMID- 26842040 TI - Meet the soft, cuddly robots of the future. PMID- 26842041 TI - Reproducibility: A tragedy of errors. PMID- 26842044 TI - Architecture: The Crick Institute unpeeled. PMID- 26842045 TI - Gene editing: Edited plants should not be patented. PMID- 26842046 TI - Governments: Balance research funds across Europe. PMID- 26842047 TI - Earth's crust: A toast to the deep-drilling idea. PMID- 26842048 TI - Range management: Tibetan wildlife hemmed in. PMID- 26842049 TI - Biodiversity law: Mauritius culls threatened fruit bats. PMID- 26842050 TI - Electrochemistry: Photocatalysts in close-up. PMID- 26842051 TI - Optical physics: Ultrashort light pulses shake atoms. PMID- 26842052 TI - Cancer: Fibroblasts for all seasons. PMID- 26842053 TI - Phylogeny: A home for Xenoturbella. PMID- 26842054 TI - A homogeneous nucleus for comet 67P/Churyumov-Gerasimenko from its gravity field. AB - Cometary nuclei consist mostly of dust and water ice. Previous observations have found nuclei to be low-density and highly porous bodies, but have only moderately constrained the range of allowed densities because of the measurement uncertainties. Here we report the precise mass, bulk density, porosity and internal structure of the nucleus of comet 67P/Churyumov-Gerasimenko on the basis of its gravity field. The mass and gravity field are derived from measured spacecraft velocity perturbations at fly-by distances between 10 and 100 kilometres. The gravitational point mass is GM = 666.2 +/- 0.2 cubic metres per second squared, giving a mass M = (9,982 +/- 3) * 10(9) kilograms. Together with the current estimate of the volume of the nucleus, the average bulk density of the nucleus is 533 +/- 6 kilograms per cubic metre. The nucleus appears to be a low-density, highly porous (72-74 per cent) dusty body, similar to that of comet 9P/Tempel 1. The most likely composition mix has approximately four times more dust than ice by mass and two times more dust than ice by volume. We conclude that the interior of the nucleus is homogeneous and constant in density on a global scale without large voids. The high porosity seems to be an inherent property of the nucleus material. PMID- 26842055 TI - Optical attosecond pulses and tracking the nonlinear response of bound electrons. AB - The time it takes a bound electron to respond to the electromagnetic force of light sets a fundamental speed limit on the dynamic control of matter and electromagnetic signal processing. Time-integrated measurements of the nonlinear refractive index of matter indicate that the nonlinear response of bound electrons to optical fields is not instantaneous; however, a complete spectral characterization of the nonlinear susceptibility tensors--which is essential to deduce the temporal response of a medium to arbitrary driving forces using spectral measurements--has not yet been achieved. With the establishment of attosecond chronoscopy, the impulsive response of positive-energy electrons to electromagnetic fields has been explored through ionization of atoms and solids by an extreme-ultraviolet attosecond pulse or by strong near-infrared fields. However, none of the attosecond studies carried out so far have provided direct access to the nonlinear response of bound electrons. Here we demonstrate that intense optical attosecond pulses synthesized in the visible and nearby spectral ranges allow sub-femtosecond control and metrology of bound-electron dynamics. Vacuum ultraviolet spectra emanating from krypton atoms, exposed to intense waveform-controlled optical attosecond pulses, reveal a finite nonlinear response time of bound electrons of up to 115 attoseconds, which is sensitive to and controllable by the super-octave optical field. Our study could enable new spectroscopies of bound electrons in atomic, molecular or lattice potentials of solids, as well as light-based electronics operating on sub-femtosecond timescales and at petahertz rates. PMID- 26842056 TI - Sub-particle reaction and photocurrent mapping to optimize catalyst-modified photoanodes. AB - The splitting of water photoelectrochemically into hydrogen and oxygen represents a promising technology for converting solar energy to fuel. The main challenge is to ensure that photogenerated holes efficiently oxidize water, which generally requires modification of the photoanode with an oxygen evolution catalyst (OEC) to increase the photocurrent and reduce the onset potential. However, because excess OEC material can hinder light absorption and decrease photoanode performance, its deposition needs to be carefully controlled--yet it is unclear which semiconductor surface sites give optimal improvement if targeted for OEC deposition, and whether sites catalysing water oxidation also contribute to competing charge-carrier recombination with photogenerated electrons. Surface heterogeneity exacerbates these uncertainties, especially for nanostructured photoanodes benefiting from small charge-carrier transport distances. Here we use super-resolution imaging, operated in a charge-carrier-selective manner and with a spatiotemporal resolution of approximately 30 nanometres and 15 milliseconds, to map both the electron- and hole-driven photoelectrocatalytic activities on single titanium oxide nanorods. We then map, with sub-particle resolution (about 390 nanometres), the photocurrent associated with water oxidation, and find that the most active sites for water oxidation are also the most important sites for charge-carrier recombination. Site-selective deposition of an OEC, guided by the activity maps, improves the overall performance of a given nanorod--even though more improvement in photocurrent efficiency correlates with less reduction in onset potential (and vice versa) at the sub-particle level. Moreover, the optimal catalyst deposition sites for photocurrent enhancement are the lower-activity sites, and for onset potential reduction the optimal sites are the sites with more positive onset potential, contrary to what is obtainable under typical deposition conditions. These findings allow us to suggest an activity-based strategy for rationally engineering catalyst-improved photoelectrodes, which should be widely applicable because our measurements can be performed for many different semiconductor and catalyst materials. PMID- 26842057 TI - Dehydration of lawsonite could directly trigger earthquakes in subducting oceanic crust. AB - Intermediate-depth earthquakes in cold subduction zones are observed within the subducting oceanic crust, as well as the mantle. In contrast, intermediate-depth earthquakes in hot subduction zones predominantly occur just below the Mohorovicic discontinuity. These observations have stimulated interest in relationships between blueschist-facies metamorphism and seismicity, particularly through dehydration reactions involving the mineral lawsonite. Here we conducted deformation experiments on lawsonite, while monitoring acoustic emissions, in a Griggs-type deformation apparatus. The temperature was increased above the thermal stability of lawsonite, while the sample was deforming, to test whether the lawsonite dehydration reaction induces unstable fault slip. In contrast to similar tests on antigorite, unstable fault slip (that is, stick-slip) occurred during dehydration reactions in the lawsonite and acoustic emission signals were continuously observed. Microstructural observations indicate that strain is highly localized along the fault (R1 and B shears), and that the fault surface develops slickensides (very smooth fault surfaces polished by frictional sliding). The unloading slope during the unstable slip follows the stiffness of the apparatus at all experimental conditions, regardless of the strain rate and temperature ramping rate. A thermomechanical scaling factor for the experiments is within the range estimated for natural subduction zones, indicating the potential for unstable frictional sliding within natural lawsonite layers. PMID- 26842058 TI - Historical nectar assessment reveals the fall and rise of floral resources in Britain. AB - There is considerable concern over declines in insect pollinator communities and potential impacts on the pollination of crops and wildflowers. Among the multiple pressures facing pollinators, decreasing floral resources due to habitat loss and degradation has been suggested as a key contributing factor. However, a lack of quantitative data has hampered testing for historical changes in floral resources. Here we show that overall floral rewards can be estimated at a national scale by combining vegetation surveys and direct nectar measurements. We find evidence for substantial losses in nectar resources in England and Wales between the 1930s and 1970s; however, total nectar provision in Great Britain as a whole had stabilized by 1978, and increased from 1998 to 2007. These findings concur with trends in pollinator diversity, which declined in the mid-twentieth century but stabilized more recently. The diversity of nectar sources declined from 1978 to 1990 and thereafter in some habitats, with four plant species accounting for over 50% of national nectar provision in 2007. Calcareous grassland, broadleaved woodland and neutral grassland are the habitats that produce the greatest amount of nectar per unit area from the most diverse sources, whereas arable land is the poorest with respect to amount of nectar per unit area and diversity of nectar sources. Although agri-environment schemes add resources to arable landscapes, their national contribution is low. Owing to their large area, improved grasslands could add substantially to national nectar provision if they were managed to increase floral resource provision. This national-scale assessment of floral resource provision affords new insights into the links between plant and pollinator declines, and offers considerable opportunities for conservation. PMID- 26842059 TI - Xenacoelomorpha is the sister group to Nephrozoa. AB - The position of Xenacoelomorpha in the tree of life remains a major unresolved question in the study of deep animal relationships. Xenacoelomorpha, comprising Acoela, Nemertodermatida, and Xenoturbella, are bilaterally symmetrical marine worms that lack several features common to most other bilaterians, for example an anus, nephridia, and a circulatory system. Two conflicting hypotheses are under debate: Xenacoelomorpha is the sister group to all remaining Bilateria (= Nephrozoa, namely protostomes and deuterostomes) or is a clade inside Deuterostomia. Thus, determining the phylogenetic position of this clade is pivotal for understanding the early evolution of bilaterian features, or as a case of drastic secondary loss of complexity. Here we show robust phylogenomic support for Xenacoelomorpha as the sister taxon of Nephrozoa. Our phylogenetic analyses, based on 11 novel xenacoelomorph transcriptomes and using different models of evolution under maximum likelihood and Bayesian inference analyses, strongly corroborate this result. Rigorous testing of 25 experimental data sets designed to exclude data partitions and taxa potentially prone to reconstruction biases indicates that long-branch attraction, saturation, and missing data do not influence these results. The sister group relationship between Nephrozoa and Xenacoelomorpha supported by our phylogenomic analyses implies that the last common ancestor of bilaterians was probably a benthic, ciliated acoelomate worm with a single opening into an epithelial gut, and that excretory organs, coelomic cavities, and nerve cords evolved after xenacoelomorphs separated from the stem lineage of Nephrozoa. PMID- 26842060 TI - New deep-sea species of Xenoturbella and the position of Xenacoelomorpha. AB - The discovery of four new Xenoturbella species from deep waters of the eastern Pacific Ocean is reported here. The genus and two nominal species were described from the west coast of Sweden, but their taxonomic placement remains unstable. Limited evidence placed Xenoturbella with molluscs, but the tissues can be contaminated with prey. They were then considered deuterostomes. Further taxon sampling and analysis have grouped Xenoturbella with acoelomorphs (=Xenacoelomorpha) as sister to all other Bilateria (=Nephrozoa), or placed Xenacoelomorpha inside Deuterostomia with Ambulacraria (Hemichordata + Echinodermata). Here we describe four new species of Xenoturbella and reassess those hypotheses. A large species (>20 cm long) was found at cold-water hydrocarbon seeps at 2,890 m depth in Monterey Canyon and at 1,722 m in the Gulf of California (Mexico). A second large species (~10 cm long) also occurred at 1,722 m in the Gulf of California. The third large species (~15 cm long) was found at ~3,700 m depth near a newly discovered carbonate-hosted hydrothermal vent in the Gulf of California. Finally, a small species (~2.5 cm long), found near a whale carcass at 631 m depth in Monterey Submarine Canyon (California), resembles the two nominal species from Sweden. Analysis of whole mitochondrial genomes places the three larger species as a sister clade to the smaller Atlantic and Pacific species. Phylogenomic analyses of transcriptomic sequences support placement of Xenacoelomorpha as sister to Nephrozoa or Protostomia. PMID- 26842063 TI - A novel interactive educational system in the operating room--the IE system. AB - BACKGROUND: The shortage of surgeon is one of the serious problems in Japan. To solve the problem, various efforts have been undertaken to improve surgical education and training. However, appropriate teaching methods in the operating room have not been well established. The aim of this study is to assess the utility of a novel interactive educational (IE) system for surgical education on urologic surgeries in the operating room. METHODS: A total of 20 Japanese medical students were educated on urologic surgery using the IE system in the operating room. The IE system consists of two parts. The first is three-dimensional (3D) magnified vision of the operative field using a 3D head-mounted display and a 3D endoscope. The second is interactive educative communication between medical students and surgeons using a small-sized wireless communication device. The satisfaction level with the IE system and the physical burden on medical students was examined via questionnaire. RESULTS: All students utilized the IE system in urologic surgery and responded to the survey. Most students were satisfied with the IE system. They also felt more welcomed by the surgeon when using the IE system than when not using it. No major unpleasant symptoms were observed but five students (25 %) experienced mild eye fatigue as a result of viewing the medical images. CONCLUSIONS: The IE system has the potential to motivate students to become interested in surgery and could be an efficient method of surgical education in the operating room. PMID- 26842062 TI - Repair of Avascular Meniscus Tears with Electrospun Collagen Scaffolds Seeded with Human Cells. AB - The self-healing capacity of an injured meniscus is limited to the vascularized regions and is especially challenging in the inner avascular regions. As such, we investigated the use of human meniscus cell-seeded electrospun (ES) collagen type I scaffolds to produce meniscal tissue and explored whether these cell-seeded scaffolds can be implanted to repair defects created in meniscal avascular tissue explants. Human meniscal cells (derived from vascular and avascular meniscal tissue) were seeded on ES scaffolds and cultured. Constructs were evaluated for cell viability, gene expression, and mechanical properties. To determine potential for repair of meniscal defects, human meniscus avascular cells were seeded and cultured on aligned ES collagen scaffolds for 4 weeks before implantation. Surgical defects resembling "longitudinal tears" were created in the avascular zone of bovine meniscus and implanted with cell-seeded collagen scaffolds and cultured for 3 weeks. Tissue regeneration and integration were evaluated by histology, immunohistochemistry, mechanical testing, and magentic resonance imaging. Ex vivo implantation with cell-seeded collagen scaffolds resulted in neotissue that was significantly better integrated with the native tissue than acellular collagen scaffolds or untreated defects. Human meniscal cell-seeded ES collagen scaffolds may therefore be useful in facilitating meniscal repair of avascular meniscus tears. PMID- 26842064 TI - Glioblastoma in long-term survivors of acute lymphoblastic leukemia: Report of two cases. AB - Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. Second neoplasms as late effects of therapy for ALL have been recognized as a significant clinical issue given the increasing number of long-term survivors of ALL, because they can be the cause of death in such cases. In contrast, glioblastoma (GBM) is the most common primary brain tumor in adults. It is a malignant brain tumor that most often occurs in elderly patients, and GBM in young adults or adolescents appears to be rare. Here, we describe our experience of two cases of GBM in young long-term survivors of ALL, and emphasize the necessity of careful follow up of patients treated for ALL for the potential occurrence of central nervous system second neoplasms, especially when the patients have previously undergone cranial radiotherapy. PMID- 26842065 TI - Enhancing reciprocal partner support to prevent perinatal depression and anxiety: a Delphi consensus study. AB - BACKGROUND: Systematic reviews have established that partner support protects against perinatal mood problems. It is therefore a key target for interventions designed to prevent maternal and paternal depression and anxiety. Nonetheless, the extant literature is yet to be translated into specific actions that parents can implement. Prevention efforts aiming to facilitate reciprocal partner support within the couple dyad need to provide specific guidance on how partners can support one another to reduce their vulnerability to perinatal depression and anxiety. METHOD: Two panels of experts in perinatal mental health (21 consumer advocates and 39 professionals) participated in a Delphi consensus study to establish how partners can support one another to reduce their risk of developing depression and anxiety during pregnancy and the postpartum period. RESULTS: A total of 214 recommendations on how partners can support each other were endorsed by at least 80 % of both panels as important or essential in reducing the risk of perinatal depression and anxiety. The recommendations were grouped under the following categories: becoming a parent, supporting each other through pregnancy and childbirth, communication, conflict, division of labor, practical support, emotional support, emotional closeness, sexual satisfaction, using alcohol and drugs, encouraging self-care, developing acceptance, and help-seeking. CONCLUSION: This study established consensus between consumers and professionals in order to produce a set of guidelines on how partners can support each other to prevent depression and anxiety during pregnancy and following childbirth. It is hoped that these guidelines will inform the development of perinatal depression and anxiety prevention efforts. PMID- 26842066 TI - Prospective stratification of patients at risk for emergency department revisit: resource utilization and population management strategy implications. AB - BACKGROUND: Estimating patient risk of future emergency department (ED) revisits can guide the allocation of resources, e.g. local primary care and/or specialty, to better manage ED high utilization patient populations and thereby improve patient life qualities. METHODS: We set to develop and validate a method to estimate patient ED revisit risk in the subsequent 6 months from an ED discharge date. An ensemble decision-tree-based model with Electronic Medical Record (EMR) encounter data from HealthInfoNet (HIN), Maine's Health Information Exchange (HIE), was developed and validated, assessing patient risk for a subsequent 6 month return ED visit based on the ED encounter-associated demographic and EMR clinical history data. A retrospective cohort of 293,461 ED encounters that occurred between January 1, 2012 and December 31, 2012, was assembled with the associated patients' 1-year clinical histories before the ED discharge date, for model training and calibration purposes. To validate, a prospective cohort of 193,886 ED encounters that occurred between January 1, 2013 and June 30, 2013 was constructed. RESULTS: Statistical learning that was utilized to construct the prediction model identified 152 variables that included the following data domains: demographics groups (12), different encounter history (104), care facilities (12), primary and secondary diagnoses (10), primary and secondary procedures (2), chronic disease condition (1), laboratory test results (2), and outpatient prescription medications (9). The c-statistics for the retrospective and prospective cohorts were 0.742 and 0.730 respectively. Total medical expense and ED utilization by risk score 6 months after the discharge were analyzed. Cluster analysis identified discrete subpopulations of high-risk patients with distinctive resource utilization patterns, suggesting the need for diversified care management strategies. CONCLUSIONS: Integration of our method into the HIN secure statewide data system in real time prospectively validated its performance. It promises to provide increased opportunity for high ED utilization identification, and optimized resource and population management. PMID- 26842067 TI - Changes in the expression of the human adenine nucleotide translocase isoforms condition cellular metabolic/proliferative status. AB - Human cells express four mitochondrial adenine nucleotide translocase (hANT) isoforms that are tissue-specific and developmentally regulated. hANT1 is mainly expressed in terminally differentiated muscle cells; hANT2 is growth-regulated and is upregulated in highly glycolytic and proliferative cells; and hANT3 is considered to be ubiquitous and non-specifically regulated. Here, we studied how the expression of hANT isoforms is regulated by proliferation and in response to metabolic stimuli, and examined the metabolic consequences of their silencing and overexpression. In HeLa and HepG2 cells, expression of hANT3 was upregulated by shifting metabolism towards oxidation or by slowed growth associated with contact inhibition or growth-factor deprivation, indicating that hANT3 expression is highly regulated. Under these conditions, changes in hANT2 mRNA expression were not observed in either HeLa or HepG2 cells, whereas in SGBS preadipocytes (which, unlike HeLa and HepG2 cells, are growth-arrest-sensitive cells), hANT2 mRNA levels decreased. Additionally, overexpression of hANT2 promoted cell growth and glycolysis, whereas silencing of hANT3 decreased cellular ATP levels, limited cell growth and induced a stress-like response. Thus, cancer cells require both hANT2 and hANT3, depending on their proliferation status: hANT2 when proliferation rates are high, and hANT3 when proliferation slows. PMID- 26842068 TI - Pharmacological removal of serum amyloid P component from intracerebral plaques and cerebrovascular Abeta amyloid deposits in vivo. AB - Human amyloid deposits always contain the normal plasma protein serum amyloid P component (SAP), owing to its avid but reversible binding to all amyloid fibrils, including the amyloid beta (Abeta) fibrils in the cerebral parenchyma plaques and cerebrovascular amyloid deposits of Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). SAP promotes amyloid fibril formation in vitro, contributes to persistence of amyloid in vivo and is also itself directly toxic to cerebral neurons. We therefore developed (R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC), a drug that removes SAP from the blood, and thereby also from the cerebrospinal fluid (CSF), in patients with AD. Here we report that, after introduction of transgenic human SAP expression in the TASTPM double transgenic mouse model of AD, all the amyloid deposits contained human SAP. Depletion of circulating human SAP by CPHPC administration in these mice removed all detectable human SAP from both the intracerebral and cerebrovascular amyloid. The demonstration that removal of SAP from the blood and CSF also removes it from these amyloid deposits crucially validates the strategy of the forthcoming 'Depletion of serum amyloid P component in Alzheimer's disease (DESPIAD)' clinical trial of CPHPC. The results also strongly support clinical testing of CPHPC in patients with CAA. PMID- 26842070 TI - [Treatment of tumor pain: by the nearest specialist]. PMID- 26842069 TI - The effectiveness of workplace dietary interventions: protocol for a systematic review and meta-analysis. AB - BACKGROUND: The lack of evidence of the role of workplaces as settings for behaviour change delivery and the failure to recognise and address the complexity of the work environment has been acknowledged. This systematic review and meta analysis will identify the effectiveness of dietary interventions in the workplace facilitating an understanding of what works, why and how by identifying key components of and examining the theoretical models of behaviour change underpinning successful dietary interventions in the workplace. METHODS/DESIGN: We will conduct searches in MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL and PubMed for studies that assess dietary interventions based within workplace settings in any country, of any length of time or duration of follow-up. We will include all randomised controlled trials (RCTs), non-randomised controlled trials (NRCTs), controlled before-after studies (CBAs) and interrupted time series (ITS) studies with a control group. Risk of bias of included studies will be assessed using a tool adapted from the Cochrane Public Health Review Group's recommended Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Meta-analysis will be conducted if appropriate, or a narrative synthesis will be conducted following the ESRC Narrative Synthesis Guidance. DISCUSSION: This paper outlines the study protocol for a systematic review and meta-analysis that will identify, critically appraise, and summarise the relevant evidence on the effectiveness and implications of interventions to promote healthier dietary behaviours in the workplace. This review will give an overview of the evidence and provide a guide for development of interventions promoting dietary behaviour change in workplaces. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015015175. PMID- 26842071 TI - [Complex regional pain syndrome in nerve root compression and after spinal surgery]. AB - Complex regional pain syndrome (CRPS) is an extremely painful and partially disabling disease. It often occurs secondary to trauma, but also spontaneously. The emergence of CRPS has been reported following nerve root compression and/or spinal surgery, but its incidence is unknown. In this article, the present knowledge about the incidence of CRPS in the context of nerve root compression and spine surgery is reviewed and therapeutic and diagnostic consequences are discussed. PMID- 26842072 TI - [Differentiation between "nonpalliative" and "palliative" treatment of tumor pain is desirable]. PMID- 26842074 TI - Experiences of homosexual patients' access to primary health care services in Umlazi, KwaZulu-Natal. AB - BACKGROUND: Homosexual patients are affected by social factors in their environment, and as a result may not have easy access to existing health care services. Prejudice against homosexuality and homosexual patients remains a barrier to them seeking appropriate healthcare. The concern is that lesbians and gays might delay or avoid seeking health care when they need it because of past discrimination or perceived homophobia within the health care thereby putting their health at risk. AIM OF THE STUDY: The aim of the study was to explore and describe the experiences of homosexual patients utilising primary health care (PHC) services in Umlazi in the province ofKwaZulu-Natal (KZN). METHOD: A qualitative, exploratory, descriptive study was conducted which was contextual innature. Semi-structured interviews were conducted with 12 participants. The findings of this study were analysed using content analysis. RESULTS: Two major themes emerged from the data analysis, namely, prejudice against homosexual patients by health care providers and other patients at the primary health care facilities, and, homophobic behaviour from primary health care personnel. CONCLUSION: Participants experienced prejudice and homophobic behaviour in the course of utilising PHC clinics in Umlazi, which created a barrier to their utilisation of health services located there. Nursing education institutions, in collaboration with the National Department of Health, should introduce homosexuality and anti-homophobia education programmes during the pre-service and in-service education period. Such programmes will help to familiarise health care providers with the health care needs of homosexual patients and may decrease homophobic attitudes. PMID- 26842073 TI - Is superior tibiofibular joint resection necessary in extraarticular knee resection for sarcomas? A systematic review. AB - BACKGROUND: Sarcomas infiltrating the knee joint require extraarticular resection to achieve wide margins. Opinions differ as to whether the superior tibiofibular joint (STFJ) is part of the knee joint and should be removed in the course of extraarticular resection. Thus, we investigated the frequency of communication between the tibiofemoral joint (TFJ) and the STFJ, and the reported local recurrence rates (LRR) following extraarticular knee resection. METHODS: A systematic literature review on STFJ and TFJ communication and local recurrence rates following extraarticular knee resections was undertaken. RESULTS: Cadaver studies detected communication between the TFJ and STFJ in 10-64% of the cases. Direct arthrography with physical loading verified a 100% communication rate. Regarding the extent of extraarticular knee resection, two institutions where the STFJ was resected had a LRR of 4-8%, while studies from another three where the STFJ was not routinely resected reported a LRR of 0-21%. CONCLUSIONS: Since the literature reports about a 100% communication rate between the TFJ and the STFJ, resection of the STFJ in patients with sarcomas involving the knee joint would seem to be indicated, although it is not clear whether resection of the STFJ reduces local recurrence rates. PMID- 26842075 TI - Clinical learning experiences of male nursing students in a Bachelor of Nursing programme: Strategies to overcome challenges. AB - BACKGROUND: Male nursing students are faced with more challenges in the clinical setting than their female counterparts. The ways in which male nurses are viewed and received by nursing staff and patients have an impact on how they perceive themselves and their role in the profession. These perceptions of self have a significant impact on their self-esteem. This study was conducted to explore the clinical learning experiences of male nursing students at a university during their placement in clinical settings in the Western Cape Province, and how these experiences impacted on their self-esteem. OBJECTIVES: To describe the learning experiences of male nursing students during placement in clinical settings, and how these impact on their self-esteem. METHOD: A qualitative, exploratory study was conducted. Purposive sampling was used to select participants. Three focus group (FG) discussions, consisting of six participants per group, were used to collect data. Data analysis was conducted by means of Coliazzi's (1978) seven steps method of qualitative analysis. STUDY FINDINGS: The following three major themes were identified: experiences that related to the constraints in the learning environment, the impact on the self-esteem, and the social support of students working in a female-dominated profession. CONCLUSION: Male nurses should be supported in nursing training, as the rate at which males enter the profession is increasing. PMID- 26842076 TI - Expectations of youth victims of violence regarding health care professionals leading them to wellness in South Africa. AB - BACKGROUND: Many youth victims of violence report for treatment at the health care facilities in the Western Cape Province of South Africa. It was unclear what the youth expected regarding how they could be led towards wellness by health care professionals following an incident of violence (R1.1). OBJECTIVES: This study sought to explore and describe the expectations of the youth victims of violence with regards to health care professionals (R1.2) leading them to wellness in a selected rural community. METHOD: A qualitative, exploratory, descriptive and contextual design was used. Nine focus group discussions were conducted with 58 (23 males, 35 females) purposefully selected youth victims of violence between the ages of 15 and 19. Data analysis was done through open coding. Ethics clearance was received from the University Ethics Committee prior to the study being conducted. RESULTS: Findings indicated that the youth victims of violence expect the health care professionals (professional nurses, doctors and social workers) working in their community to act as role models, demonstrate a professional attitude, provide health education, provide confidential counselling services, and establish school and community outreach programmes. CONCLUSION: This study provides evidence that youth victims of violence have important expectations from health care professionals concerning their wellness. Hence, health care professionals should focus on designing and implementing interventions targeting these expectations. PMID- 26842077 TI - Perceptions of female teenagers in the Tshwane District on the use of contraceptives in South Africa. AB - BACKGROUND: Perceptions of female teenagers in the Tshwane District contribute to the nonuseand or discontinued use of contraceptives as evidenced by increased levels of unplanned pregnancies. OBJECTIVE: The objective of this study was to explore and describe the perceptions of female teenagers in the Tshwane District on the use of contraceptives. METHODS: A qualitative, explorative, descriptive approach was followed in this study. The population comprised of pregnant female teenagers who were purposively selected. Data were collected using unstructured individual interviews on a face-to-face encounter in a natural setting. Data were analysed using the discourse method of data analysis. RESULTS: The following perceptions on the use of contraceptives emerged: Perceptions on the use of contraceptives, emotions, contraceptive effects, social pressure and education on contraceptives. Teenagers' perceptions were predominantly negative with unfounded fears. Though the teenagers were aware of the importance of the use of contraceptives, motivation to pursue contraception was lacking. Teenagers verbalised to be uncommitted as well. CONCLUSION: Various perceptions of female teenagers in the Tshwane District on the use of contraceptives were explored and described. It was noted that all the teenagers interviewed had great remorse and feelings of guilt regarding their behaviour of not using contraceptives.Their need for re-education was cited and seen as motivational enough to encourage the use of contraceptives at primary health care settings. Therefore, the study recommended that health education programmes should be restructured to effectively influence the female teenagers'perceptions positively and to promote the use of contraceptives. PMID- 26842078 TI - Use of the step-up action research model to improve trauma-related nursing educational practice. AB - BACKGROUND: A lack of authentic learning opportunities influence the quality of emergency training of nursing students. The purpose of this article is to describe how the step-up action research model was used to improve the quality of trauma-related educational practice of undergraduate nursing students. OBJECTIVES: To reduce deaths caused by trauma, healthcare workers should be competent to provide emergency care and collaborate effectively with one another. METHOD: A simulated mass casualty incident, structured to support the integration of theory into practice, became a more rigorous action research activity which focused on the quality improvement of the mass casualty incident. RESULTS: The results indicated improved student learning; partnership appreciation; improved student coping mechanisms, and increased student exposure. Quality emergency training thus results in better real-life collaboration in emergency contexts. CONCLUSION: The step-up action research model proved to be a collaborative and flexible process. To improve the quality and rigour of educational programmes it is therefore recommended that the step-up action research model be routinely used in the execution of educational practices. PMID- 26842079 TI - Learning end-of-life care within a constructivist model: Undergraduate nursing students' experiences. AB - BACKGROUND: Although nursing education aims to equip nursing students to provide care to dying patients and their families, nurses often feel ill-prepared to cope with the emotional labour involved in end-of-life care. OBJECTIVES: The aim of the study was to explore and describe nursing students' experiences of end-of life care through experiential learning within a constructivist educational model. METHOD: A qualitative, descriptive design was used. As part of introducing experiential learning, innovative educational practices were initiated during a second year level undergraduate nursing module on end-of-life care. Qualitative data on second-year nursing students' experiences were collected through written reflections and analysed using open coding. RESULTS: The themes that emerged revealed participants' sensory and emotional experiences during the learning opportunities. Participants reflected on what they learnt and clarified their values related to death and dying. They indicated how they would apply the new meanings constructed in clinical practice. CONCLUSION: A constructivist educational model of experiential learning holds potential to enhance value clarification and nursing students' sensory and emotional awareness of death and dying. Experiential learning is recommended to develop nursing students' competency inproviding end-of-life care. PMID- 26842080 TI - Access to information and decision making on teenage pregnancy prevention by females in Tshwane. AB - BACKGROUND: The increase in the number of teenage pregnancies and its negative consequences has encouraged various researchers to explore the possible causes of teenage pregnancy. Findings from previously-conducted research have indicated different preventable factors that predispose female teenagers to pregnancy, such as staff attitudes and the lack of information resulting from poor access to health facilities. OBJECTIVE: To explore and describe access to information and decision making on teenage pregnancy prevention by females using a primary healthcare clinic in Tshwane, South Africa. METHOD: In this study, the researchers used a descriptive qualitative and exploratory research design to explore and describe the verbal reports regarding prevention of teenage pregnancy by females using a primary healthcare clinic in Tshwane, South Africa. Face-to face semistructured interviews were conducted with 15 female participants aged between 15 and 26, who had been pregnant once or more during their teens. RESULTS: Two themes emerged, namely, access to information and decision making by female teenagers. Five categories that emerged were: access to information on pregnancy prevention; ignoring of provided information; the use of alternative medicine with hormonal contraception; personal reasons for use and non-use of contraception; and decisions made by teenagers to not fall pregnant. Females in this study fell pregnant in their teens, even though they had access to information. CONCLUSION: Given the complexity of this problem, female teenagers should use their families as primary sources of information for reproductive health promotion and educational institutions should build on this to aid the prevention of teenage pregnancy. PMID- 26842082 TI - The development of an implementation framework for service-learning during the undergraduate nursing programme in the Western Cape Province. AB - BACKGROUND: Service-learning (SL) is a contested field of knowledge and issues of sustainability and scholarship have been raised about it. The South African Higher Education Quality Committee (HEQC) has provided policy documents to guide higher education institutions (HEIs) in the facilitation of SL institutionalisation in their academic programmes. An implementation framework was therefore needed to institutionalise the necessary epistemological shifts advocated in the national SL policy guidelines. OBJECTIVES: This article is based on the findings of a doctoral thesis that aimed at developing an SL implementation framework for the School of Nursing (SoN) at the University of the Western Cape (UWC). METHOD: Mixed methods were used during the first four phases of the design and developmenti ntervention research model developed by Rothman and Thomas. RESULTS: The SL implementation framework that was developed during Phase 3 specified the intervention elements to address the gaps that had been identified by the core findings of Phases 1 and 2. Four intervention elements were specified for the SL implementation framework. The first intervention element focused on the assessment of readiness for SL institutionalisation. The development of SL capacity and SL scholarship was regarded as the pivotal intervention element for three of the elements: the development of a contextual SL definition, an SL pedagogical model, and a monitoring and evaluation system for SL institutionalisation. CONCLUSION: The SL implementation framework satisfies the goals of SL institutionalisation, namely to develop a common language and a set of principles to guide practice, and to ensure the allocation of resources in order to facilitate the SL teaching methodology.The contextualised SL definition that was formulated for the SoN contributes to the SL operationalisation discourse at the HEI. PMID- 26842081 TI - Knowledge of nurses regarding dysphagia in patients post stroke in Namibia. AB - BACKGROUND: Stroke patients commonly experience dysphagia post stroke. Complications of dysphagia include aspiration leading to chest infection and pneumonia, malnutrition, dehydration, and a subsequent increased risk of death. Its early diagnosis and management is an important prerequisite for recovery from stroke during the rehabilitation phase. As nurses are the first health personnel that interact with a patient post stroke, it is important that they are knowledgeable and skilled in the screening of these patients for dysphagia. OBJECTIVE: The aim of the study was to determine the knowledge and factors associated with knowledge of nurses regarding dysphagia in stroke patients. METHODS: The study used a quantitative survey to determine the knowledge of the nurses employed at an intermediate hospital in Namibia. A convenient sample of 182 participants completed a self-administered questionnaire with closed-ended questions, which was developed by the researcher. The data was analysed using descriptive and inferential statistics. RESULTS: The findings of the study confirmed that nurses have a moderate knowledge of the signs, symptoms, and complications of dysphagia, but poor knowledge about its management.Training and experience in the care of dysphagia patients was a stronger predictor of knowledge than the initial qualification or years of experience as a nurse. CONCLUSION: Post basic training in dysphagia would better equip nurses to manage stroke patients in the acute phase. PMID- 26842083 TI - Perceptions of educators regarding the implementation of the health promotion programme manuals for children in schools in Makapanstad, South Africa. AB - BACKGROUND: Health promoting schools focus on, amongst other things, preventing leading causes of death such as Sexually Transmitted Infections (STI's), Human Immune Deficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS), a sedentary lifestyle and creating conditions that are conducive to health through health education. AIM: This study explored the perceptions of educators regarding implementation of the health promotion programme manuals in selected schools of the Makapanstad community. METHOD: A qualitative, exploratory, descriptive and contextual design was utilised in this study. Four schools were selected to participate in the study. Purposive sampling was used to select educators from these schools who were actively involved in the health promotion programme. Data collection was taken through focus group interviews. One focus group comprised of eight participants who were interviewed three times. The focus group interviews were conducted until data were saturated. Data were analysed using an adaptation of Tesch's method. The eight steps of Tesch's method enabled researchers to systematically analyse and organise data using colour coding to develop data into categories, sub-categories and themes. RESULTS AND CONCLUSION: The themes that emerged during data analysis were: the perceptions of educators regarding health promotion programme manuals before implementation of manuals, and the perceptions of educators regarding health promotion programme manuals after the implementation of manuals. Introducing health promotion materials to the schools served as a point of departure for developing personal skills and creating a supportive environment for health in schools. The health promotion manual assisted the educators to attain appropriate health promotion information. PMID- 26842084 TI - Experiences of registered nurses with regard to accessing health information at the point-of-care via mobile computing devices. AB - BACKGROUND: The volume of health information necessary to provide competent health care today has become overwhelming. Mobile computing devices are fast becoming an essential clinical tool for accessing health information at the point of-care of patients. OBJECTIVES: This study explored and described how registered nurses experienced accessing information at the point-of-care via mobile computing devices (MCDs). METHOD: A qualitative, exploratory, descriptive and contextual design was used. Ten in-depth interviews were conducted with purposively sampled registered nurses employed by a state hospital in the Nelson Mandela Bay Municipality (NMBM). Interviews were recorded, transcribed verbatim and analysed using Tesch's data analysis technique. Ethical principles were adhered to throughout the study. Guba's model of trustworthiness was used to confirm integrity of the study. RESULTS: Four themes emerged which revealed that the registered nurses benefited from the training they received by enabling them to develop, and improve, their computer literacy levels. Emphasis was placed on the benefits that the accessed information had for educational purposes for patients and the public, for colleagues and students. Furthermore the ability to access information at the point-of-care was considered by registered nurses as valuable to improve patient care because of the wide range of accurate and readily accessible information available via the mobile computing device. CONCLUSION: The registered nurses in this study felt that being able to access information at the point-of-care increased their confidence and facilitated the provision of quality care because it assisted them in being accurate and sure of what they were doing. PMID- 26842085 TI - Adult learning: What nurse educators need to know about mature students. AB - BACKGROUND: Most nurse educators regard students who enter postgraduate studies as adult learners capable of self-direction and independent learner behaviour. Therefore, a mismatch between the nurse educator's expectation of adult learners and actual adult learner conduct may result in disappointment and even frustration for both educator and learner. PURPOSE: This article is a report of a secondary analysis of data that were collected to explore the high-fidelity simulation learning experiences of a group of postgraduate nursing students.The secondary analysis was done to determine whether adult learners who bring professional knowledge and experience to a postgraduate learning environment displayed adult learner conduct as proposed by educational theorist Malcolm Knowles. METHOD: Using a qualitative descriptive research design, data were gathered from 18 postgraduate nursing students who participated in high-fidelity simulation in a nursing school at a higher education institution in South Africa. The nominal group technique was used to collect the students' ideas about improving their simulation learning experiences. A secondary qualitative analysis of the primary nominal group data was done. FINDINGS: Data either confirmed or belied adult learner behaviour. Although the findings suggested self-directed and independent learner behaviour, they also revealed behaviour evident of dependence on the educator. CONCLUSION: Mature students have well established ways of thinking and doing that may hinder learning. Educators have to support adult learners in developing effective learning techniques in order to maximise the benefits of their experience and knowledge by fostering independence and self direction. PMID- 26842086 TI - Accessibility and availability of the Female Condom2: Healthcare provider's perspective. AB - BACKGROUND: Despite the acceptability of the Female Condom2 (FC2) as a contraceptive method by some women, it remains inaccessible and unavailable to the majority of women because of affordability, training, distribution and marketing strategies. The FC2 affords women dual protection and the option to negotiate safe sex. OBJECTIVE: This paper explores and describes the perspective of the healthcare providers regarding accessibility and availability of the FC2 as a contraceptive method in the Tshwane district. METHOD: The study used an explorative, descriptive, and qualitative design. Data were collected from 26 healthcare providers who were purposively selected. In-depth face-to-face interviews were conducted with these healthcare providers in the Tshwane district. Tesch's method of open coding was used for data analysis. RESULTS: Two main themes emerged, namely, the availability of the FC2 and the knowledge o fthe healthcare providers. The findings of this study indicated that the availability of the FC2 remains a challenge because of factors such as lack of affordability, inefficient procurement and lack of distribution measures. The condoms are also not available at strategic points so as to ensure accessibility. Insufficient knowledge amongst healthcare providers was described as a barrier which affects the quality of training of the service users. CONCLUSIONS: It is evident that the FC2 is not yet available in all healthcare settings, therefore strategies to safeguard accessibility and availability of the FC2 as a contraceptive method are recommended. PMID- 26842087 TI - The impact of an indigenous proverb on women's mental health: A phenomenological approach. AB - BACKGROUND: Proverbs and idioms represent cultural and societal beliefs and values inherited from the forefathers. An example is lebitla la mosadi ke bogadi. Over many decades African people have used such ancient instructions to counsel women to be resilient in their marriages thus impacting on their mental health. OBJECTIVE: The purpose of this article was to explore and describe that proverb and its impact on women's mental health. METHOD: Hermeneutic phenomenology was used to explore and describe the prover band its impact on indigenous women's mental health. The population included married, divorced, widowed and single women who were attending social clubs or networks in the cities of Tshwane and Johannesburg. Snowball and purposive sampling was used to select 57 participants. Five face-to-face interviews and eight focus groups interviews were conducted. Colaizzi's data analysis method was used to analyse data. RESULTS: Oppression and stigmatisation of women and their families and harmful effects that may result in death were identified as having an impact on women's mental health. Some women shared that they were oppressed in many ways. In addition, they feared stigmatisation should they wish to divorce. They constantly lived in fear of being harmed or killed by their spouses. CONCLUSION: There was a need for nurses to develop awareness regarding cultural issues so that women are better served in primary healthcare settings. Women who are suspected of experiencing abuse, should be screened for abuse so that they can be assisted accordingly. PMID- 26842088 TI - Assessing the use of contraceptives by female undergraduate students in a selected higher educational institution in Gauteng. AB - BACKGROUND: Unplanned pregnancies amongst students at higher education institutions are a major concern worldwide, including South Africa. Apart from various social and psychological challenges, unplanned pregnancies affect students' objectives of achieving academic success. Research undertaken in the United States of America (USA) indicates that around 80% of female students in institutions of higher education between ages 18 and 24 are sexually active. OBJECTIVES: To assess and describe the use of contraceptives by undergraduate female students in a selected higher educational institution in Gauteng. METHOD: A cross-sectional, descriptive, quantitative design was used. A total of 400 female undergraduate students were requested to respond to a self-administered questionnaire. Stratified random sampling was used to select the participants. They were selected systematically from two campuses. Data were entered using an excel sheet at the Department of Statistics, and analysed using the Statistical Analysis Software programme, (SAS version 9.3), of the Department of Statistics' higher educational institutions. RESULTS: A total of 74%females indicated they were sexually active, 79%of whom reported using contraceptives. The most common used methods were oral contraceptives at 38%, and 25% for male condoms. The most commonly known methods were condoms at 84%, and the oral contraceptive at 68%. The knowledge of condom use to prevent sexually transmitted diseases was high at 91%. CONCLUSION: Inadequate knowledge and awareness on some contraceptive methods was found. Thus, educational programmes to increase students' knowledge on the use of all contraceptive methods are urgently needed. PMID- 26842089 TI - Bridging the gap between self-directed learning of nurse educators and effective student support. AB - BACKGROUND: Self-directed learning requires the ability to identify one's own learning needs, develop and implement a plan to gain knowledge and to monitor one's own progress. A lifelong learning approach cannot be forced, since it is in essence an internally driven process. Nurse educators can, however, act as role models to empower their students to become independent learners by modelling their own self-directed learning and applying a number of techniques in supporting their students in becoming ready for self-directed learning. OBJECTIVES: The aim of the article is to describe the manifestations and implications of the gap between self-directed learning readiness of nurse educators and educational trends in supporting students. METHOD: An instrumental case study design was used to gain insight into the manifestations and implications of self-directed learning of nurse educators. Based on the authentic foci of various critical incidents and literature, data were collected and constructed into a fictitious case. The authors then deductively analysed the case by using the literature on self-directed learning readiness as departure point. Four constructs of self-directed learning were identified, namely internal motivation, planning and implementation, self-monitoring and interpersonal communication. Supportive strategies were identified from the available literature. RESULTS: Nine responses by nurse educators based on the fictitious case were analysed.Analysis showed that readiness for self-directed learning in terms of the identified constructswas interrelated and not mutually exclusive of one other. CONCLUSION: The success of lifelong learning is the ability to engage in self-directed learning which requires openness to learning opportunities, good self-concept, taking initiative and illustrating independence in learning. Conscientiousness, an informed acceptance of a responsibility for one's own learning and creativity, is vital to one's future orientation towards goal directed learning. Knowledge and understanding of one's own and students' selfdirected learning abilities are critical for nurse educators. In the nursing profession, it has been shown that self-directed learning by the nurse educators has a direct relationship towards the development of a lifelong learning approach by their students. Supporting students towards becoming self-directed learners throughout their professional life, in turn, will impact directly on the quality of nursing and midwifery practice. (Article to follow). PMID- 26842090 TI - Parents perceptions of stress in a neonatal intensive care unit in Rwanda. AB - BACKGROUND: Having a newborn infant hospitalised in the neonatal intensive care unit (NICU) is an unexpected and stressful event for a family. A number of potential stressors to which family members of patients in these units may be exposed have been identified, although no studies about this issue have been conducted in Rwanda. AIM: The aim of this study was to describe and analyse parental perception of stress that resulted from having their infant admitted to a NICU in Kigali, Rwanda. METHOD: A quantitative survey was used to describe and analyse parents' perceptions of stress when they had an infant admitted to a NICU. The Parental Stress Scale: Neonatal Intensive Care Unit was used to measure the level of stress that those parents experienced. RESULTS: The results indicated that parents experienced stress from having their infants cared for in a NICU. The most stressful events were the appearance and behaviour of the baby with a mean score of 4.02, whilst the subscale items related to sights and sounds were found to be the least significant source of stress for parents with a mean score of 2.51. In addition, the current study found that parents' age, educational level, occupation, and infant birth weight were associated with parental stress. CONCLUSION: The study established that a range of factors was responsible for parental stress when a baby was cared for in a NICU. Identification of these factors could enable health professionals from a hospital in Kigali, Rwanda, to facilitate parents' adjusting and coping. PMID- 26842091 TI - Reflections on clinical practice whilst developing a portfolio of evidence: Perceptions of undergraduate nursing students in the Western Cape, South Africa. AB - BACKGROUND: In order to develop clinical judgement, nurses should be encouraged to become analytical and critical thinkers. Development of a portfolio of evidence (PoE) of reflection on clinical experiences is one of the strategies that can be used to enhance analytical and critical thinking amongst nursing students. Students' perceptions of the process are important in order to encourage their reflective practice. PoE compilation at a school of nursing at a university in the Western Cape includes evidence of students' clinical learning which they present in a portfolio. The students are expected to reflect on their clinical learning experiences and include these reflections in their portfolios. OBJECTIVE: To describe the perceptions of fourth-year nursing students regarding reflective practice whilst compiling their PoEs. METHOD: A qualitative design was used to explore the perceptions of registered fourth-year nursing students with regard to their reflective practice whilst compiling their PoEs. Purposive sampling was used for selection of participants. Three focus group discussions were held, each consisting of six to eight participants. Data saturation was reached during the third meeting. Tesch's method of data analysis was used. RESULTS: Findings revealed that reflection enabled the learners to gain experience and identify challenges related to the expected events and tasks carried out at the hospitals and in the classroom whilst developing their PoE. CONCLUSION: The compilation of a PoE was a good teaching and learning strategy, and the skills, experience and knowledge that the participants in this study acquired boosted their self-esteem, confidence and critical thinking. Reflection also assisted in self-directed learning. PMID- 26842092 TI - Nurse educators' experiences of case-based education in a South African nursing programme. AB - BACKGROUND: A school of nursing at a university in the Western Cape experienced an increase in student enrolments from an intake of 150 students to 300 students in the space of one year. This required a review of the teaching and learning approach to ensure that it was appropriate for effective facilitation of large classes. The case-based education (CBE) approach was adopted for the delivery of the Bachelor of Nursing programme in 2005. AIM: The aim of the study was to explore nurse educators' experiences, current practices and possible improvements to inform best practice of CBE at the nursing school in the Western Cape. METHODS: A participatory action research method was applied in a two day workshop conducted with nurse educators in the undergraduate nursing programme. The nominal group technique was used to collect the data. RESULTS: Three themes emerged from the final synthesis of the findings, namely: teaching and learning related issues, student issues and teacher issues. Amongst other aspects, theory and practice integration, as well as the need for peer support in facilitation of CBE, were identified as requiring strengthening. CONCLUSION: It was concluded that case-based education should continue to be used in the school, however, more workshops should be arranged to keep educators updated and new staff orientated in respect of this teaching and learning approach. PMID- 26842093 TI - Using mobile phones and social media to facilitate education and support for rural-based midwives in South Africa. AB - BACKGROUND: Empirical studies show the value of mobile phones as effective educational tools to support learning in the nursing profession, predominantly in high income countries. PROBLEM STATEMENT: The rapidly increasing prevalence of mobile phone technology in Africa nourishes hopes that these tools could be equally effective in lowly resourced contexts, specifically in efforts to achieve the health-related Millennium Development goals. The purpose of this study was to investigate the perception and use of mobile phones as educational and professional tools by nurses in lowly resourced settings. METHODOLOGY: A quantitative survey using self-administered questionnaires was conducted of rural advanced midwives. RESULTS: Fifty-six nurses (49.6%) from the 113 rural-based midwives attending an advanced midwifery training programme at the University of KwaZulu-Natal, South Africa, filled in a questionnaire. The results showed that, whilst nurses regarded their technology competences as low and although they received very little official support from their educational and professional institutions, the majority frequently used mobile functions and applications to support their work and learning processes. They perceived mobile devices with their voice, text, and email functions as important tools for the educational and professional activities of searching for information and engaging with facilitators and peers from work and study contexts. To a lesser extent, the use of social networks, such as WhatsApp and Facebook, were also reported. CONCLUSION AND RECOMMENDATION: It is concluded that educational institutions should support the appropriate use of mobile phones more systematically; particularly in relation to the development of mobile network literacy skills. PMID- 26842094 TI - Turnover of professional nurses at Mokopane Hospital in the Limpopo Province, South Africa: Experiences of nursing unit managers. AB - BACKGROUND: Staff turnover of professional nurses remains a concern for public and private hospitals management because it has an impact on the morale of nurses and it may also lead to poor patient care. OBJECTIVES: The objectives of this study were to explore and describe the experiences of nursing unit managers with regard to the turnover of professional nurses who were under their supervision. METHOD: A qualitative, explorative, descriptive research design was used to determine the experiences of nursing unit managers related to the turnover of professional nurses. Data collection was done by using semi-structured one-to-one interviews with professional nurses .Two groups of participants were interviewed: Those working day duty (n = 9) and those working night duty (n = 3) who were at work on the anticipated days for data collection. RESULTS: The findings revealed that every unit was experiencing a shortage of professional nurses, which caused other nurses to work overtime with an inevitable increase in workload. That led to tiredness, conflict amongst professional nurses, job dissatisfaction, and absenteeism which compromised nursing care. This resulted in patient dissatisfaction and sometimes led to deaths that could have been prevented. CONCLUSION: It is recommended that staff turnover should be addressed by the hospital top management implementing several strategies. For example, top management could ensure that staff members work in a healthy environment with resources that they need during the provision of care, address the effects of the staff turnover, support the staff members and refrain from putting pressure on nursing unit managers whilst they are attending to problems. PMID- 26842095 TI - The perceptions of African women regarding natural menopause in Mamelodi, Tshwane district. AB - BACKGROUND: The majority of South African aging population are women, who spend late adulthood experiencing natural menopause. Despite the government spending billions of rand on different services for ageing women, menopausal challenges to African women still receive little attention. OBJECTIVES: The aim of the study was to explore and describe the perceptions of African women regarding natural menopause, in order to propose recommendations for health and social support systems for women in Mamelodi, Tshwane district. METHOD: A qualitative, exploratory, descriptive and contextual design was used to conduct the study. The population of the study consisted of menopausal women, between the ages 45 and 60 years or more, visiting the clinics for collection of chronic medication and othe rhealth assessment. Individual face-to-face interviews were conducted, using a semi-structured interview guide to collect data. Tesch's method of qualitative data analysis was used in the study. RESULTS: The main theme that emerged from the study was 'attitude toward menopause', which was supported by cultural beliefs and experience. The African menopausal women expressed the importance of health support systems that will meet their needs within their context. CONCLUSION: Women's health programs and educational health information at facilities should include menopausal education to promote and improve health of all African menopausal women during their adulthood. There is a need to establish a women's health support group network within communities to share menopausal experiences with peers. The training and education curriculum of healthcare providers should include detailed menopause in order to provide comprehensive, congruent care. PMID- 26842096 TI - Indigenous practices of pregnant women at Dilokong hospital in Limpopo province, South Africa. AB - BACKGROUND: Indigenous practices (IPs) are experiences generated by people who are living in a specific regional context and cultural group. IPs are shaped by cultural traits that are passed from one generation to the next. IPs practices are rooted and embedded in society and, therefore, the practices become part of the people's lifestyle. It is difficult to try and change these practices as people have adhered to them throughout their entire lives. The believe system plays a major role in health care seeking behaviour of individuals because they are informed by the IPs that are observed in their environment. OBJECTIVES: To explore and describe the IPs of pregnant women at Dilokong hospital in Limpopo province. METHOD: A qualitative, descriptive, explorative and contextual research design was used for the participants to describe the IPs used by pregnant women. Data were collected through unstructured one-on-one interviews. RESULTS: The following four themes with sub-themes emerged from the data: IPs based on ancestral knowledge; IPs based on spiritual diviners versus church principles; restricted practices versus instructions followed during pregnancy; and labour and IPs during labour and delivery. CONCLUSION: IPs are regarded as an honourable health intervention by traditional health practitioners (THPs), families and pregnant women. IPs like cords around women's waists are still observed during physical examinations. However, there is a reduction of prescribed indigenous oral medication used to accelerate labour because of their potential toxicity. PMID- 26842097 TI - Validation of the integration of HIV and AIDS related nursing competencies into the undergraduate nursing curriculum in South Africa. AB - BACKGROUND: Being in its fourth decade, HIV remains an epidemic that requires combined efforts for the global fight. The strategies planned and implemented in the fight against HIV include reversing and halting the spread of HIV, increasing health care access, and strengthening the health care system. South Africa has made the fight one of its top priorities, and has developed plans to increase the role of nurses in the management of HIV, demonstrating its willingness, commitment and progress in the fight against HIV. OBJECTIVE: This article presents the validation process conducted to confirm the integration and mapping of the HIV and AIDS related nursing competencies into the four-year Bachelor of Nursing programme at a university in South Africa. METHODS: This study adopted a constructivist paradigm, using a qualitative approach, applyingthe design step of the process model of curriculum development, to validate the inte gration of the mapped HIV and AIDS related nursing competencies into the undergraduate nursing curriculum. RESULTS: For each competency, outcomes were developed for each year. Participants confirmed completeness of outcomes and appropriateness of the mapping of the HIV and AIDS related outcomes into the nursing curriculum, as well as the feasibility and practicability of the integration. CONCLUSION: Required resources for integration of HIV and AIDS related nursing competencies, such as human resources and nurse educators' continued personal development were identified, as well as barriers to integration, and measures to eliminate them were discussed. The importance of integration of HIV and AIDS nursing competencies into the curriculum was reiterated. PMID- 26842098 TI - Experiences of nurses caring for mental health care users in an acute admission unit at a psychiatric hospital in the Western Cape Province. AB - BACKGROUND: Caring for mental health care users (MHCUs) with mental illnesses is a major task that confronts nurses globally. It has been argued that caring for this group of patients is accompanied by unique challenges. Despite the available abundance of data about nursing patients suffering from mental illnesses, little is known about the lived experiences of nurses who care for MHCUs in acute admission units in the Western Cape province. OBJECTIVES: This study's aim is to explore and describe the lived experiences of nurses who care for MHCUs in an acute admission unit at a psychiatric hospital in the Western Capeprovince. METHODS: A qualitative, descriptive, phenomenological study was conducted. A purposive sampling procedure was applied which resulted in a sample that comprised eight nurses. Indepth, individual, semi-structured interviews were conducted with these eight participants. Interviews were audio-recorded and transcribed verbatim and the researcher utilised Collaizzi's method to analyse collected data. RESULTS: Both positive and negative experiences were reported. Positive experiences werethe recovery of patients, teamwork, and passion for caring. Negative experiences were thefeelings of being unappreciated and unsupported by authorities. Physical assault by MHCUs,shortage of staff, increased workload and burnout was also reported. CONCLUSIONS: In-service training about management of aggression needs to be provided,debriefing sessions to deal with burnout needs to be arranged, and research to quantify levelsof burnout should be conducted. PMID- 26842099 TI - Students' voices on spiritual care at a Higher Education Institution in the Western Cape. AB - BACKGROUND: Nurses have a moral obligation to ensure holistic care of patients, inclusive of the spiritual dimension. However, there seems to be a void in the teaching and learning of spiritual care in nursing curricula. Despite the South African Nursing Council being in favour of holistic nursing, there are no measures in place to ensure implementation of spiritual care, hence its practice is not standardised in nursing education in South Africa. Currently, the undergraduate nursing curriculum does not provide clear direction on how spiritual care in nursing should be integrated and the reason for this is not clear. It appears that the lack of professional regulation, difficulties in definition and the personalised nature of spiritual practice are partly responsible for the practice being barely enforced and scarcely practised by students in clinical placements. The aim of the study was to develop a practice theory for teaching-learning of spiritual care in the undergraduate nursing programme. OBJECTIVES: The study objective was to describe and explore the students' experiencs of teaching-learning of spiritual care in the undergraduate nursing programme. METHODS: A qualitative, explorative, descriptive and contextual design with purposive sampling was used. The sample consisted of undergraduate nursing students at a University in the Western Cape Province. Measures for trustworthiness were applied. RESULTS: The findings indicated a need to provide support, a conducive learning environment and structure for teaching, learning and practice of spiritual care. CONCLUSION: There is a need for formal education regarding spiritual care in nursing. PMID- 26842101 TI - The clinical usefulness of serum procalcitonin level in patients with scrub typhus. PMID- 26842100 TI - The internal jugular vein as an alternative venous access for a revision of a fractured implantable cardioverter-defibrillator lead. PMID- 26842102 TI - Development of Kaposi sarcoma and hemophagocytic lymphohistiocytosis associated with human herpesvirus 8 in a renal transplant recipient. PMID- 26842103 TI - Recurrent pyogenic liver abscess as a presenting manifestation of colorectal cancer. PMID- 26842105 TI - Acute cor pulmonale due to pulmonary tumor thrombotic microangiopathy in two patients with breast cancer. PMID- 26842104 TI - Ankylosing spondylitis associated with primary aldosteronism in a middle-aged woman. PMID- 26842106 TI - A confusing case of multiple sclerosis and central nervous system graft versus host disease. PMID- 26842108 TI - Developmental dysplasia of the hip: usefulness of next generation genomic tools for characterizing the underlying genes - a mini review. AB - Developmental dysplasia of the hip (DDH) is one of the most common skeletal anomalies. DDH encompasses a spectrum of the disorder ranging from minor acetabular dysplasia to irreducible dislocation, which may lead to premature arthritis in later life. Involvement of genetic factors underlying DDH became evident when several studies reported chromosomal loci linked to DDH in families with multiple affected individuals. Moreover, using association studies, variants in genes involved in chondrogenesis and joint formation have been shown to be associated with DDH. At least, one study identified a pathogenic variant in the chemokine receptor gene in DDH. No genetic analysis has been reported or carried out in DDH patients from the Middle East. Here, we review the literature related to genetics of DDH and emphasized the usefulness of new generation technologies in identifying genetic variants underlying DDH in consanguineous families. PMID- 26842109 TI - Veno-Venous Extracorporeal Membrane Oxygenation (V V ECMO): Indications, Preprocedural Considerations, and Technique. AB - Veno-venous extracorporeal membrane oxygenation (V V ECMO) has been used for refractory respiratory failure. We describe the indications, technical aspects, and outcomes of placing V V ECMO in adults using a dual-lumen, single-cannula catheter. PMID- 26842107 TI - Mirtazapine added to selective serotonin reuptake inhibitors for treatment resistant depression in primary care (MIR trial): study protocol for a randomised controlled trial. AB - BACKGROUND: People with depression are usually managed in primary care and antidepressants are often the first-line treatment, but only one third of patients respond fully to a single antidepressant. This paper describes the protocol for a randomised controlled trial (MIR) to investigate the extent to which the addition of the antidepressant mirtazapine is effective in reducing the symptoms of depression compared with placebo in patients who are still depressed after they have been treated with a selective serotonin reuptake inhibitor (SSRI) or serotonin and noradrenaline reuptake inhibitor (SNRI) for at least 6 weeks in primary care. METHODS/DESIGN: MIR is a two-parallel group, multi-centre, pragmatic, placebo controlled, randomised trial with allocation at the level of the individual. Eligible participants are those who: are aged 18 years or older; are currently taking an SSRI/SNRI antidepressant (for at least 6 weeks at an adequate dose); score >= 14 on the Beck Depression Inventory (BDI-II); have adhered to their medication; and meet ICD-10 criteria for depression (assessed using the Clinical Interview Schedule-Revised version). Participants who give written, informed consent, will be randomised to receive either oral mirtazapine or matched placebo, starting at 15 mg daily for 2 weeks and increasing to 30 mg daily thereafter, for up to 12 months (to be taken in addition to their usual antidepressant). Participants, their GPs, and the research team will all be blind to the allocation. The primary outcome will be depression symptoms at 12 weeks post randomisation, measured as a continuous variable using the BDI-II. Secondary outcomes (measured at 12, 24 and 52 weeks) include: response (reduction in depressive symptoms (BDI-II score) of at least 50% compared to baseline); remission of depression symptoms (BDI-II <10); change in anxiety symptoms; adverse effects; quality of life; adherence to antidepressant medication; health and social care use, time off work and cost-effectiveness. All outcomes will be analysed on an intention-to-treat basis. A qualitative study will explore patients' views and experiences of either taking two antidepressants, or an antidepressant and a placebo; and GPs' views on prescribing a second antidepressant in this patient group. DISCUSSION: The MIR trial will provide evidence on the clinical and cost-effectiveness of mirtazapine as an adjunct to SSRI/SNRI antidepressants for patients in primary care who have not responded to monotherapy. TRIAL REGISTRATION: EudraCT Number: 2012-000090-23 (Registered January 2012); ISRCTN06653773 (Registered September 2012). PMID- 26842110 TI - Inherited ion channel diseases: a brief review. AB - Ion channelopathies are diseases caused by dysfunctional ion channels that may lead to sudden death. These diseases can be either acquired or inherited. The main phenotypes observed in patients carrying these heritable arrhythmia syndromes are congenital long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, and short QT syndrome. In the recent years, tremendous progress has been made in the recognition, mechanisms, and treatment of these diseases. The goal of this review is to provide an overview of the main phenotypes, genetic underpinnings, risk stratification, and treatment options for these so-called cardiac ion channelopathies. PMID- 26842111 TI - Sudden cardiac death in China: current status and future perspectives. AB - Sudden cardiac death (SCD) is a major cause of mortality worldwide. Similar to the number of SCDs in western countries including the USA, the number of SCDs in China is ~544,000 annually. However, there are significant differences in patient characteristics between Chinese primary prevention population and U.S. primary prevention population. In contrast to western countries where implantable cardioverter-defibrillator (ICD) devices have been well adopted as a major effective method for both primary and secondary prevention of SCD, China has a low prevalence of ICD utilization (~1.5 device per 1 million people). Socioeconomic and political factors, awareness and knowledge of SCD, and the difference in disease patterns have led to the underutilization of ICD in China. China, as the most populated and the second largest economic country in the world, has now taken variable approaches to address this pressing health problem and enhances the delivery of lifesaving therapies, including arrhythmia ablation and medical treatment besides ICD, to patients who are at risk of SCD. PMID- 26842112 TI - Catheter ablation of peri-nodal and pulmonary veno-atrial substrates: should it be cool? AB - Catheter cryoablation (CRYO) is an alternative approach to radiofrequency (RF) ablation in the treatment of cardiac arrhythmias. The favourable lesion characteristics of CRYO and its unique properties of cryomapping and cryoadhesion make this newer approach especially suitable for the treatment of peri-nodal substrates, such as atrioventricular nodal re-entrant tachycardia and septal accessory pathway, and pulmonary veno-atrial substrate in atrial fibrillation. This review aims to present and discuss the data on the use of catheter CRYO for these substrates with special emphasis on its efficacy and safety compared with RF ablation. PMID- 26842113 TI - Asian strategy for stroke prevention in atrial fibrillation. AB - Atrial fibrillation (AF) has become a major health burden in Asia. It is estimated that in year 2050 Asia will have 72 million AF patients, and 2.9 million among them will suffer from AF-associated stroke. Asian AF patients have similar cardiovascular co-morbidities as westerns, and the recently developed CHA2DS2-VASc score remains valid in predicting stroke risk in Asians, outperforming other scoring systems. There is little evidence supporting a role of aspirin in preventing AF-associated stroke in Asians. Warfarin is effective for the prevention of stroke in Asians, but is very difficult to use. Warfarin induced bleeding events are more common in Asians. Four major clinical trials have been performed to test non-vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin in the stroke prevention in AF. Warfarin produced higher risk of major bleeding and intra-cranial haemorrhage in Asians compared with those in non Asians, even though anticoagulation intensity was lower in Asians. All these trials consistently demonstrated that NOACs were superior or non-inferior to warfarin. The benefits of NOACs were especially robust in Asians. The relative risk reduction in most of the efficacy endpoints and the safety endpoints was numerically greater in Asians than in non-Asians. There was no evidence of increased risk of gastro-intestinal bleeding associated with NOACs in Asians. Unless in a few conditions when NOACs are contraindicated, NOACs are preferred medications in the stroke prevention for AF in Asians. PMID- 26842115 TI - Deterioration of left ventricular systolic function in extended Pacing to Avoid Cardiac Enlargement (PACE) trial: the predictive value of early systolic dyssynchrony. AB - AIMS: Biventricular (BiV) pacing was superior to right ventricular apical (RVA) pacing at extended follow-up in the Pacing to Avoid Cardiac Enlargement (PACE) trial. Early pacing-induced systolic dyssynchrony (DYS) might be related to mid term result. However, it remains unknown whether early pacing-induced DYS can predict long-term reduction of left ventricular (LV) systolic function. METHODS AND RESULTS: Patients with standard pacing indications and normal LV ejection fraction (LVEF) were randomized either to BiV (n = 89) or RVA (n = 88) pacing. Seventy-four patients in the RVA group and 72 in the BiV pacing group completed follow-up longer than 2 years. Serial echocardiography was performed with DYS assessed by tissue Doppler imaging, and the early pacing-induced DYS was defined as >33 ms by using standard deviation of the time to peak systolic velocity (Dyssynchrony Index) in a 12-segment model of LV at 1 month. There were 46 (32%) patients having early pacing-induced DYS that was more prevalent in the RVA pacing group than that in the BiV pacing group (50.7 vs. 12.3%, chi(2) = 25.1, P < 0.001) despite the similar DYS between the two groups at baseline (30 +/- 13 vs. 26 +/- 11 ms, P = 0.051). At a median follow-up of 4.8 years, patients developing early DYS had lower LVEF (53.2 +/- 9.4 vs. 60.9 +/- 8.0%, P < 0.001) and larger LV end-systolic volume (40.3 +/- 23.7 vs. 29.3 +/- 13.4 mL, P < 0.001) than those without DYS. Significant EF reduction (defined as >=5%) occurred in 71.7% (33 in 46) of patients with DYS, but only in 30% (30 in 100) in those without DYS (chi(2) = 22.4, P < 0.001). Further analysis showed that both DYS at 1 month [odds ratio (OR): 3.113, P = 0.013] and RVA pacing (OR: 7.873, P < 0.001) independently predicted the deterioration of LV systolic function with pacing period of 4.8 years. CONCLUSION: Early pacing-induced DYS is a significant predictor of reduction of LV systolic function for long-term pacing, which could be prevented by BiV pacing at relatively long-period follow-up. CLINICAL TRIAL REGISTRATION: Centre for Clinical Trials number, CUHK_CCT00037 (URL: http://www.cct.cuhk.edu.hk/Registry/publictrialrecord.aspx?trialid=CUHK_CCT00037) PMID- 26842114 TI - Subclinical atrial fibrillation and stroke: insights from continuous monitoring by implanted cardiac electronic devices. AB - Nearly one out of five strokes is associated with atrial fibrillation (AF). Atrial fibrillation is often intermittent and asymptomatic. Detection of AF after cryptogenic stroke will likely change therapy from antiplatelet to oral anticoagulation agents for secondary stroke prevention. A critical step is to convert 'covert' AF into electrocardiogram documented AF. External rhythm recording devices have registered a high incidence of AF to occur after a cryptogenic stroke, but are limited by short duration of continuous recordings. Invasive cardiac monitoring using insertable leadless cardiac monitors are sensitive means to identify subclinical AF (SCAF) after cryptogenic stroke, and AF has been reported to occur in 8.9% of these patients by 6 months in one study. It will be more attractive to identify SCAF before a stroke occurs. Recent series in pacemaker and implantable cardioverter-defibrillator (ICD) recipients showed that short episodes of SCAF increased stroke risk, with odds ratio ~2.2-3.1 compared with those without SCAF recorded. However, temporal sequence of recorded SCAF and stroke occurrence was uncertain, and the overall stroke risk was lower compared with patients with clinical AF at similar risk scores. This article reviews the incidence and clinical role of using implanted devices to detect SCAF and discusses the implication of SCAF so detected in primary and secondary stroke prevention. PMID- 26842116 TI - Prevalence and prognosis of Brugada electrocardiogram patterns in an elderly Han Chinese population: a nation-wide community-based study (HALST cohort). AB - AIMS: The exact world-wide prevalence of Brugada electrocardiogram (ECG) pattern is still unclear, especially in adults aged 55 years and older. METHODS AND RESULTS: The study was conducted as part of the Healthy Aging Longitudinal Study in Taiwan (HALST). Using a stratified random sampled method, a sample of community-dwelling subjects was recruited from seven community-based regions across Taiwan. All enrolled subjects were follow-up annually and cause of death was documented by citizen death records. A total of 5214 subjects were enrolled (male/female: 2530/2684) with a mean age of 69 +/- 8 years. The overall prevalence of Brugada ECG patterns was 3.32%. Four subjects carried spontaneous Type 1 Brugada ECG pattern, 68 carried Type 2, and 101 carried Type 3. Compared with the world-wide average prevalence of Brugada ECG patterns, the prevalence of spontaneous Type 1 Brugada ECG pattern in subjects from the HALST cohort was similar (0.077 vs. 0.07%) and the combined prevalence of Types 2 and 3 Brugada ECG pattern was 10 times higher (3.24 vs. 0.28%) even the mean age of study subjects was significantly higher (69 +/- 8 vs. 35 +/- 8, P < 0.001). However, all-cause mortality and cardiac mortality rates were not significantly different between subjects with and without Brugada ECG patterns during the 4-year follow up (log-rank test, P = 0.21, 0.32, respectively). CONCLUSION: The prevalence of Brugada ECG pattern in adults aged 55 years and older in Taiwan was higher than the average world-wide prevalence but was not associated with increased mortality. PMID- 26842117 TI - First clinical experience of the safety and feasibility of total subcutaneous implantable defibrillator in an Asian population. AB - AIMS: The safety and feasibility of a subcutaneous implantable cardioverter defibrillator (S-ICD) has been demonstrated in the treatment of life-threatening ventricular tachyarrhythmias (VT). Nonetheless, its safety and feasibility in an Asian population with smaller body-build is unclear. METHODS AND RESULTS: Twenty one Asian patients who underwent S-ICD from 1 April 2014 to 2 February 2015 in five institutions in Hong Kong and Singapore were retrospectively reviewed. Twenty-one patients with a mean age of 50.0 +/- 14.1 years (range 29-77 years, 82.6% male) were included. Among them, 17 (81.0%) were Chinese, 3 (14.3%) were Malay, and 1 (4.8%) was Indian. Their mean body mass index was 23.0 +/- 4.0 kg/m(2). An S-ICD was implanted for primary and secondary prevention in 13 (61.9%) and 8 (38.1%) patients, respectively. The indications included Brugada syndrome (n = 6, 28.6%), ischaemic cardiomyopathy (CMP, n = 6, 28.6%), dilated CMP (n = 4, 19.0%), hypertrophic CMP (n = 2, 9.5%), and idiopathic ventricular fibrillation (n = 2, 9.5%). Three patients (14.3%) had prior infected transvenous ICD. There were no acute complications but eight wound complications (persistent wound bleeding requiring intervention = 2; delayed wound healing: upper sternal wound = 3; generator site = 1; local wound infection = 2) were observed in six (28.2%) patients. After a mean follow-up of 107.2 +/- 81.3 days (range of 14-254 days), one patient underwent three successful appropriate shocks for treatment of VTs. No inappropriate therapy was documented. CONCLUSION: Our initial experience shows that S-ICD is a feasible treatment for VT among an Asian population with smaller body-build. There was nonetheless a relatively high rate of wound complications. PMID- 26842118 TI - Comparison of non-vitamin K antagonist oral anticoagulants and warfarin on clinical outcomes in atrial fibrillation patients with renal dysfunction. AB - AIMS: We aimed to compare the efficacy and safety between non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in atrial fibrillation (AF) patients according to renal dysfunction. METHODS AND RESULTS: We analysed 1319 patients who had been taken oral anticoagulants. They were classified into patients taking NOACs (n = 326) and warfarin (n = 993). Renal dysfunction was defined as the estimated glomerular filtration rate <60 mL/min by using the Chronic Kidney Disease Epidemiology Collaboration equation. The composite clinical outcomes were defined as the composite of death, hospitalization, and new-onset strokes. Safety outcomes were composed of major and minor bleeding. Subgroup analyses for clinical and safety outcomes were performed according to renal dysfunction during median 596 (506-612) follow-up days. The prevalence of renal dysfunction was similar between the two groups. The incidences of death, hospitalization, and strokes were not different between the two groups. However, the incidences of major bleeding was significantly higher in patients taking warfarin. In the subgroup analysis with renal dysfunction, the use of NOACs significantly improved the composite clinical outcomes (adjusted hazard ratio, HR, 0.30, 95% confidence interval, CI, 0.11-0.77, interaction P = 0.018) and major bleeding (adjusted HR 0.18, 95% CI 0.07-0.45, interaction P = 0.199) even after the covariate adjustment. However, in patients without renal dysfunction, there were no differences in the incidences of the composite clinical outcomes between the two groups. CONCLUSIONS: The benefit of NOACs was more prominent in AF patients with renal dysfunction than without renal dysfunction. These results suggest that NOACs as the first choice oral anticoagulant in AF patients with renal dysfunction. PMID- 26842119 TI - The 12-lead electrocardiogram and risk of sudden death: current utility and future prospects. AB - More than 100 years after it was first invented, the 12-lead electrocardiogram (ECG) continues to occupy an important place in the diagnostic armamentarium of the practicing clinician. With the recognition of relatively rare but important clinical entities such as Wolff-Parkinson-White and the long QT syndrome, this clinical tool was firmly established as a test for assessing risk of sudden cardiac death (SCD). However, over the past two decades the role of the ECG in risk prediction for common forms of SCD, for example in patients with coronary artery disease, has been the focus of considerable investigation. Especially in light of the limitations of current risk stratification approaches, there is a renewed focus on this broadly available and relatively inexpensive test. Various abnormalities of depolarization and repolarization on the ECG have been linked to SCD risk; however, more focused work is needed before they can be deployed in the clinical arena. The present review summarizes the current knowledge on various ECG risk markers for prediction of SCD and discusses some future directions in this field. PMID- 26842120 TI - The role of variability in night-time mean heart rate on the prediction of ventricular arrhythmias and all-cause mortality in implantable cardioverter defibrillator patients. AB - AIMS: This study was to use implantable cardioverter defibrillator (ICD) home monitoring (HM) feature to evaluate the role of mean night-time heart rate (MNHR) in the occurrence of ventricular arrhythmias (VAs) and mortality. METHODS AND RESULTS: This study retrospectively analysed clinical and ICD device data in 318 ICD patients. Data of the first 30-day MNHR (recorded 02:00-06:00 am) by HM were collected. The average and standard deviation of 30-day MNHR (AVHR and SDHR, respectively) were then determined in each patient. The primary endpoint was appropriate ICD treatment of VAs. The secondary endpoint was all-cause mortality. During a mean follow-up period of 32 +/- 10 months, 179 of the 318 patients (56.3%) experienced VAs, 123 patients (38.7%) were treated by ICD shocks, and 37 patients (11.6%) died. The overall SDHR in this study cohort was 4.5 +/- 3.0 bpm. Based on the receiver operating characteristic curve, the cut-off value of SDHR = 3.685 bpm was identified to predict VAs. In the Kaplan-Meier survival, SDHR >= 3.685 bpm was associated with increased VAs [hazard ratio (HR) = 1.885; 95% confidence interval (CI) = 1.362-2.609; P < 0.001], shock events (HR = 1.637; 95% CI = 1.11-2.414; P = 0.013), all-cause mortality (HR = 2.42; 95% CI = 1.266 4.627; P = 0.008), and the combined endpoints (HR = 1.872; 95% CI = 1.365-2.567; P < 0.001). In univariate and multivariate Cox models (adjusting for clinical factors), SDHR >= 3.685 bpm was still an independent predictor for all endpoints. CONCLUSION: In ICD population, SDHR >= 3.685 bpm was an independent predictor for VAs and all-cause mortality. PMID- 26842122 TI - Blunted rate-dependent left atrial pressure response during isoproterenol infusion in atrial fibrillation patients with impaired left ventricular diastolic function: a comparison to pacing. AB - AIMS: A heart rate (HR)-dependent haemodynamic linkage between peak left atrial (LA) pressure during sinus rhythm (LAPpeak) and estimated left ventricular (LV) filling pressure (E/Em) has not yet been explored. We hypothesized that rate dependent LAPpeak response differs depending on E/Em in patients with atrial fibrillation (AF). METHODS AND RESULTS: A total of 331 patients (68.0% male, 59.8 +/- 10.8 years old) undergoing radiofrequency catheter ablation (RFCA) for AF were included, and their LAPpeak in sinus rhythm was recorded at the beginning of the procedure and at the HRs of 90, 100, 110, and 120 b.p.m. during right atrial pacing and isoproterenol (ISO-stress) infusion. We compared LAPpeak changes between patients with E/Em >= 15 (n = 58) and those with <15 (n = 273). (i) The patterns of pacing rate-dependent LAPpeak increase were similar in both the E/Em < 15 (P < 0.001) and E/Em >= 15 groups (P = 0.002). (ii) The ISO-stress reduced LAPpeak in patients with E/Em < 15 (P = 0.015), but not in those with E/Em >= 15 (P = 0.582). (iii) Paradoxical ISO-stress LAP elevation in patients with E/Em >= 15 was independently associated with 1-year follow-up E/Em reduction (B = -4.07, 95% CI -5.41 to -2.72, P < 0.001). Coexistence of E/Em >= 15 and ISO-stress LAP elevation increased specificity in predicting 1-year follow-up E/Em reduction after AF ablation than E/Em alone. CONCLUSION: Isoproterenol LAPpeak reduction was blunted in patients with impaired LV diastolic function estimated by E/Em >= 15. The improvement of LV diastolic dysfunction 1 year after AF ablation was independently associated with both paradoxical ISO-stress LAP elevation and E/Em >= 15 at the time of procedure. CLINICALTRIALSGOV: NCT02138695. PMID- 26842121 TI - Red cell distribution width as a novel predictor for clinical outcomes in patients with paroxysmal atrial fibrillation. AB - AIMS: Elevated red cell distribution width (RDW) has been known to be associated with adverse long-term outcomes in patients with cardiovascular diseases. We aimed to evaluate relationship between RDW values and clinical outcomes in patients with paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: We analysed 567 patients who were newly diagnosed as paroxysmal AF. Clinical outcomes were analysed after median 4.8 (3.4-6.9) years follow-up. The composite clinical outcomes were defined as the composite of death, hospitalization due to heart failure, and new-onset stroke. Bleeding events were composed of major and minor bleeding. The relationship of RDW with clinical outcomes was assessed using continuous or categorical variables as quartiles: <12.8, 12.8-13.2, 13.3-13.8, and >=13.9%. Patients with the highest RDW quartile were the oldest and had more frequent history of heart failure. CHA2DS2-VASc score was increased along with increasing RDW quartiles (1.75 +/- 1.48 vs. 1.77 +/- 1.63 vs. 1.87 +/- 1.61 vs. 2.33 +/- 1.65, P = 0.008). Incidence of new-onset stroke (log-rank P = 0.032), the composite clinical outcomes (log-rank P = 0.014), and bleeding events (log rank P = 0.001) were increased as increasing RDW quartiles. Multivariate analysis identified that RDW was a significant predictor for new-onset stroke [adjusted hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.06-1.65, P = 0.015], the composite clinical outcomes (adjusted HR 1.21, 95% CI 1.03-1.41, P = 0.017), and bleeding events (adjusted HR 1.36, 95% CI 1.13-1.64, P = 0.001). CONCLUSIONS: RDW can be a new, useful, novel predictor of clinical and safety outcomes in patients with paroxysmal AF. PMID- 26842123 TI - Effect of the electrograms density in detecting and ablating the tip of the rotor during chronic atrial fibrillation: an in silico study. AB - AIMS: Identification in situ of arrhythmogenic mechanisms could improve the rate of ablation success in atrial fibrillation (AF). Our research group reported that rotors could be located through dynamic approximate entropy (DApEn) maps. However, it is unknown how much the spatial resolution of catheter electrodes could affect substrates localization. The present work looked for assessing the electrograms (EGMs) spatial resolution needed to locate the rotor tip using DApEn maps. METHODS AND RESULTS: A stable rotor in a two-dimensional computational model of human atrial tissue was simulated using the Courtemanche electrophysiological model and implementing chronic AF features. The spatial resolution is 0.4 mm (150 * 150 EGM). Six different lower resolution arrays were obtained from the initial mesh. For each array, DApEn maps were constructed using the inverse distance weighting (IDW) algorithm. Three simple ablation patterns were applied. The full DApEn map detected the rotor tip and was able to follow the small meander of the tip through the shape of the area containing the tip. Inverse distance weighting was able to reconstruct DApEn maps after applying different spatial resolutions. These results show that spatial resolutions from 0.4 to 4 mm accurately detect the rotor tip position. An ablation line terminates the rotor only if it crosses the tip and ends at a tissue boundary. CONCLUSION: A previous work has shown that DApEn maps successfully detected simulated rotor tips using a high spatial resolution. In this work, it was evinced that DApEn maps could be applied using a spatial resolution similar to that available in commercial catheters, by adding an interpolation stage. This is the first step to translate this tool into medical practice with a view to the detection of ablation targets. PMID- 26842124 TI - [Emergency during pregnancy after Roux-en-Y gastric bypass]. PMID- 26842126 TI - Immunoreceptor TIGIT inhibits the cytotoxicity of human cytokine-induced killer cells by interacting with CD155. AB - T cell Ig and ITIM domain (TIGIT) is a newly identified inhibitory receptor expressed on T and natural killer (NK) cells. Cytokine-induced killer (CIK) cells express CD3 and CD56 molecules, and share functional properties with both NK and T cells. However, it remains unknown whether TIGIT is expressed in CIK cells. Here, we show that TIGIT is expressed by CIK cells and interacts with CD155. By blocking TIGIT using an anti-TIGIT functional antibody, we demonstrate that CIK cells display increased proliferation; higher cytotoxic targeting of tumor cells expressing CD155; and higher expression of interferon-gamma (IFN-gamma), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Furthermore, increases in IFN-gamma and cytotoxicity by blockade of TIGIT were reduced by blocking DNAX accessory molecule-1 (DNAM-1) signaling, implying that TIGIT exerts immunosuppressive effects by competing with DNAM-1 for the same ligand, CD155. Our results provide evidence that blockade of TIGIT may be a novel strategy to improve the cytotoxic activity of CIK cells. PMID- 26842128 TI - Organ Donation After Euthanasia: A Dutch Practical Manual. AB - Many physicians and patients do not realize that it is legally and medically possible to donate organs after euthanasia. The combination of euthanasia and organ donation is not a common practice, often limited by the patient's underlying pathology, but nevertheless has been performed >40 times in Belgium and the Netherlands since 2005. In anticipation of patients' requests for organ donation after euthanasia and contributing to awareness of the possibility of this combination among general practitioners and medical specialists, the Maastricht University Medical Center and the Erasmus University Medical Center Rotterdam have developed a multidisciplinary practical manual in which the organizational steps regarding this combined procedure are described and explained. This practical manual lists the various criteria to fulfill and the rules and regulations the different stakeholders involved need to comply with to meet all due diligence requirements. Although an ethicist was involved in writing this paper, this report is not specifically meant to comprehensively address the ethical issues surrounding the topic. This paper is focused on the operational aspects of the protocol. PMID- 26842127 TI - Lessons learned from cancer vaccine trials and target antigen choice. AB - A wide variety of tumor antigens have been targeted in cancer immunotherapy studies. Traditionally, the focus has been on commonly overexpressed antigens shared across many patients and/or tumor types. As the field has progressed, the identity of human tumor rejection antigens has broadened. Immunologic monitoring of clinical trials has slowly elucidated candidate biomarkers of immune response and clinical response, and conversely, of immune dysfunction and suppression. We have utilized MART-1/Melan-A in our melanoma studies and observed a high frequency of immune responses and several significant clinical responses in patients vaccinated with this melanosomal protein. Alpha-fetoprotein is a shared, overexpressed tumor antigen and secreted glycoprotein that we have tested in hepatocellular cancer vaccines. Our recent studies have identified immunosuppressive and immune-skewing activities of this antigen. The choice of target antigen and its form can have unexpected effects. PMID- 26842129 TI - Use of N,O-carboxymethyl chitosan to prevent postsurgical adhesions in a rabbit double uterine horn model: a randomized controlled design. AB - In previous studies, N,O-carboxymethyl chitosan has been shown to decrease the incidence and intensity of abdominal adhesions. In the present study, adhesions were induced in 220 rabbits using a double uterine horn model. Rabbits were randomized to receive an operation only or an operation+medical chitosan intraperitoneally. Twenty-two rabbits from each group were euthanized at one of five different times (Day 3, 7, 14, 28, or 42), and adhesion formation was given gross and histopathological scores. Reductions were observed in adhesion extent (P=0.0337) and tenacity (P=0.0271) as well as inflammation (P<0.0001) on Day 3 when medical chitosan was applied. Prior to Day 14, fibrosis was less obvious in the medical chitosan group (P< 0.0005). The tenacity scores were significantly lower in the medical chitosan group following Day 14 (P<.05), while the type scores were lower in the medical chitosan group following Day 28 (P<.03). Thus, medical chitosan decreased both the gross and the histopathological scores of the induced adhesions. PMID- 26842125 TI - TCR gene-modified T cells can efficiently treat established hepatitis C associated hepatocellular carcinoma tumors. AB - The success in recent clinical trials using T cell receptor (TCR)-genetically engineered T cells to treat melanoma has encouraged the use of this approach toward other malignancies and viral infections. Although hepatitis C virus (HCV) infection is being treated with a new set of successful direct anti-viral agents, potential for virologic breakthrough or relapse by immune escape variants remains. Additionally, many HCV+ patients have HCV-associated disease, including hepatocellular carcinoma (HCC), which does not respond to these novel drugs. Further exploration of other approaches to address HCV infection and its associated disease are highly warranted. Here, we demonstrate the therapeutic potential of PBL-derived T cells genetically engineered with a high-affinity, HLA A2-restricted, HCV NS3:1406-1415-reactive TCR. HCV1406 TCR-transduced T cells can recognize naturally processed antigen and elicit CD8-independent recognition of both peptide-loaded targets and HCV+ human HCC cell lines. Furthermore, these cells can mediate regression of established HCV+ HCC in vivo. Our results suggest that HCV TCR-engineered antigen-reactive T cells may be a plausible immunotherapy option to treat HCV-associated malignancies, such as HCC. PMID- 26842130 TI - Paneth cells: the hub for sensing and regulating intestinal flora. AB - The complex interplay between symbiotic bacteria and host immunity plays a key role in shaping intestinal homeostasis and maintaining host health. Paneth cells, as one of the major producers of antimicrobial peptides in the intestine under steady-state conditions, play a vital role in regulating intestinal flora. Many studies on inflammatory bowel disease (IBD)-associated genes have put Paneth cells at the center of IBD pathogenesis. In this perspective, we focus on mechanistic studies of different cellular processes in Paneth cells that are regulated by various IBD-associated susceptibility genes, and we discuss the hypothesis that Paneth cells function as the central hub for sensing and regulating intestinal flora in the maintenance of intestinal homeostasis. PMID- 26842131 TI - Health & Economic Burden of Traumatic Brain Injury in the Emergency Department. AB - OBJECTIVE: To evaluate epidemiological patterns and lifetime costs of traumatic brain injury (TBI) identified in the emergency department (ED) within a publicly insured population in Ontario, Canada, in 2009. METHODS: A nationally representative, population-based database was used to identify TBI cases presenting to Ontario EDs between April 2009 and March 2010. We calculated unit costs for medical treatment and productivity loss, and multiplied these by corresponding incidence estimates to determine the lifetime costs of identified TBI cases across age group, sex, and mechanism of injury. RESULTS: In 2009, there were more than 133,000 ED visits for TBI in Ontario, resulting in a conservative estimate of $945 million in lifetime costs. Lifetime cost estimates ranged from $279 million to $1.22 billion depending on the diagnostic criteria used to define TBI. Peak rates of TBI occurred among young children (ages 0-4 year) and the elderly (ages 85+ years). Males experienced a 53% greater rate of TBI and incurred two-fold higher costs compared with females. Falls, sports/bicyclist related injuries, and motor vehicle crashes represented 47%, 12%, and 10% of TBI presenting to ED, respectively, and accounted for a significant proportion of costs. CONCLUSIONS: This study revealed an enormous health and economic burden associated with TBI identified in the ED setting. Our findings underscore the importance of ongoing surveillance and prevention efforts targeted to vulnerable populations. More research is needed to fully appreciate the burden of TBI across a variety of health care settings. PMID- 26842132 TI - Introducing Discrete Frequency Infrared Technology for High-Throughput Biofluid Screening. AB - Accurate early diagnosis is critical to patient survival, management and quality of life. Biofluids are key to early diagnosis due to their ease of collection and intimate involvement in human function. Large-scale mid-IR imaging of dried fluid deposits offers a high-throughput molecular analysis paradigm for the biomedical laboratory. The exciting advent of tuneable quantum cascade lasers allows for the collection of discrete frequency infrared data enabling clinically relevant timescales. By scanning targeted frequencies spectral quality, reproducibility and diagnostic potential can be maintained while significantly reducing acquisition time and processing requirements, sampling 16 serum spots with 0.6, 5.1 and 15% relative standard deviation (RSD) for 199, 14 and 9 discrete frequencies respectively. We use this reproducible methodology to show proof of concept rapid diagnostics; 40 unique dried liquid biopsies from brain, breast, lung and skin cancer patients were classified in 2.4 cumulative seconds against 10 non-cancer controls with accuracies of up to 90%. PMID- 26842134 TI - Amine Directed Pd(II)-Catalyzed C-H Activation-Intramolecular Amination of N Het(aryl)/Acyl Enaminonitriles and Enaminones: An Approach towards Multisubstituted Indoles and Heterofused Pyrroles. AB - An efficient route to multisubstituted indoles has been developed through intramolecular oxidative C-H activation-amination of readily available 2 (het)aryl-3-(het)aryl/alkyl-3-(het)aryl/acylaminoacrylonitrile/enaminone precursors in the presence of either palladium acetate/cupric acetate catalytic system under oxygen atmosphere or palladium acetate/silver carbonate in the presence of pivalic acid as additive. The method is compatible with a diverse range of substituents on the aryl ring as well as at the 2- and 3-positions of the indole ring. The versatility of this method was further demonstrated by elaborating it for the synthesis of heterofused pyrroles such as thieno[2,3 b]pyrroles, thieno[3,2-b]pyrroles, pyrrolo[2,3-b]indoles, and pyrrolo[2,3 b]pyridines in good yields. Probable mechanisms for the formation of these indoles have been suggested. PMID- 26842133 TI - Theoretical and Behavioral Mediators of a Weight Loss Intervention for Men. AB - OBJECTIVE: Men are currently underrepresented in weight loss trials despite similar obesity rates, which limit our understanding about the most effective elements of treatment for men. The purpose of this study was to test the theoretical (autonomous motivation, self-efficacy, outcome expectancies, and self regulation) and behavioral (calorie intake, physical activity, self-weighing) mediators of a men-only, Internet-delivered weight loss intervention focused on innovative and tailored treatment elements specifically for men. METHOD: Data comes from a 6-month randomized trial (N = 107) testing the intervention compared to a waitlist control group. Changes in the theoretical mediators between baseline and 3 months were tested as mediators of the intervention effect on weight change at 6 months in both single and multiple mediator models. Changes in behaviors between baseline and 6 months were tested in the same manner. RESULTS: The intervention produced greater weight losses compared to the control group ( 5.57 kg +/- 6.6 vs. -0.65 kg +/- 3.3, p < 0.001) and significant changes (p's < 0.05) in most of the theoretical and behavior mediators. In multiple mediator models, changes in diet-related autonomous motivation, self-efficacy, and self regulation all significantly mediated the relationship between the intervention and weight loss. The intervention effect was also mediated by changes in dietary intake and self-weighing frequency. CONCLUSIONS: By testing the theoretical mediators of this intervention in a multiple mediator context, this study contributes to current knowledge related to the development of weight loss interventions for men and suggests that interventions should target diet-focused constructs. PMID- 26842135 TI - Activating frataxin expression by repeat-targeted nucleic acids. AB - Friedreich's ataxia is an incurable genetic disorder caused by a mutant expansion of the trinucleotide GAA within an intronic FXN RNA. This expansion leads to reduced expression of frataxin (FXN) protein and evidence suggests that transcriptional repression is caused by an R-loop that forms between the expanded repeat RNA and complementary genomic DNA. Synthetic agents that increase levels of FXN protein might alleviate the disease. We demonstrate that introducing anti GAA duplex RNAs or single-stranded locked nucleic acids into patient-derived cells increases FXN protein expression to levels similar to analogous wild-type cells. Our data are significant because synthetic nucleic acids that target GAA repeats can be lead compounds for restoring curative FXN levels. More broadly, our results demonstrate that interfering with R-loop formation can trigger gene activation and reveal a new strategy for upregulating gene expression. PMID- 26842136 TI - Spectrum of systemic bacterial infections during febrile neutropenia in pediatric oncology patients in tertiary care pediatric center. AB - BACKGROUND: Outcome of pediatric cancers has significantly improved with modern chemotherapy and good supportive care. However, febrile neutropenia remains one of the important limiting factors in these patients especially with the emergence of resistant organisms. Choosing appropriate antimicrobials is possible only if we understand the local microbial spectrum and their sensitivity pattern. AIMS: To study the likely etiologic agents and their antibiotic sensitivity pattern among systemic infections in children with cancer. SETTINGS AND DESIGN: This is a prospective study. MATERIALS AND METHODS: The study was conducted at a tertiary care center for pediatrics, in which culture samples representing blood stream infections and others like urinary tract infections sent from the Oncology services of the Hospital during the year of 2013 were analyzed. The microbiological profile and antibiotic sensitivity pattern of these isolates were studied. RESULTS: There were 89 isolates that represented blood and urinary tract infections in neutropenic patients with cancer.Out of 89 positive cultures 76 were gram negative isolates. The most common gram negative bacterial isolates were Escherichia coli 33 (37%), followed by Pseudomonas 21 (23.5%). Acinetobacter grew in 2 patients (2.2%). Extended spectrum beta-lactamases (ESBL's), carbepenem resistant and pan-resistant organisms seen in 28 (31.4%), 5 (5.6%) and 2 cases (2.3%) respectively. Over all Gram-positive organisms were 13/89 (12.3%). Staphylococcus was the most common Gram-positive organism and methicillin resistant Staphylococcus aureus seen in 5 each. CONCLUSION: Gram-negative organism is a common isolate in cancer children with febrile neutropenia, which is resistant to first-line antibiotic cefepime. Meropenem is most sensitive antibiotic and ESBL's are sensitive to piperacillin-tazobactam. PMID- 26842137 TI - Competing risk: An illustration with aspiration pneumonia in head and neck cancer patients undergoing radical radiotherapy: A biostatistician's perspective. AB - Interest in survival analysis is to look and capture the information about the occurrence of events, i.e., death. In human life different types of events may happen at the same time. Sometimes, few events completely interrupt or make subtle changes on the occurrence of an event of interest. The method to capture information about the specific event of interest along with other events is known as competing risk modeling. This paper is dedicated to explore the application of competing risk model in oncology practice. It is aimed in near future that more and more survival analysis will be performed through application of competing risk modeling instead of traditional survival analysis to generate robust statistical inference. PMID- 26842138 TI - The utility of molecular testing in the futility of definite therapy. PMID- 26842139 TI - Leptomeningeal metastasis in solid tumors with a special focus on lung cancer. AB - Leptomeningeal metastasis is a common problem in advanced solid tumor malignancies. A significant number of patients have underlying lung cancer. With the advent of better therapies, the management of leptomeningeal metastasis is gained more importance to improve survival and quality of live. This review article focuses on the epidemiology, clinical features, diagnostics and the recent management strategies directed towards leotomeningela metastasis from solid tumor, esp lung cancer. PMID- 26842140 TI - Concurrent malaria infection on anticancer therapy. PMID- 26842141 TI - H7N9 influenza: The concern in oncology. AB - Emerging influenza is at great concern at present. Since early 2013, the new emerging H7N9 influenza has been detected in China. As a new disease, it is lack for knowledge on this emerging disease. Here, the author will discuss on this new emerging influenza and concern in oncology. PMID- 26842142 TI - Microbiology, infection control and infection related outcome in pediatric patients in an oncology center in Eastern India: Experience from Tata Medical Center, Kolkata. AB - CONTEXT: Infection is a major determinant in the outcome of patients with cancer. AIMS: The aim was to know the epidemiology and outcome of patients with cancer in a cancer care center in Eastern India. SETTINGS AND DESIGN: Retrospective study of pediatric patients in Tata Medical Center, Kolkata, India. METHODS: Patients (n = 262) between the age group of 0 and 18 years were reviewed for infections and infection-related outcome (January to December 2013). STATISTICAL ANALYSIS: Modified Wald method was used to determine confidence interval of proportions. RESULTS: Gram-negative bacteria were found to be the most common cause of bloodstream infections (BSIs) (56.4%), followed by Gram-positive cocci (34.5%), and Candida species (9.1%). Carbapenem-resistance was noted among 24% of Gram negative bacilli (GNB), and extended-spectrum beta-lactamase among 64% of GNBs. A single case of Vibrio cholerae septicemia was also noted. No case of vancomycin resistant Enterococcus was observed, whereas only two cases of methicillin resistant Staphylococcus aureus bacteremia (1/3 of all Staphylococcus aureus bacteremia) were detected. Escherichia coli, followed by Klebsiella, Pseudomonas, and Acinetobacter were the predominant organisms detected in BSIs. Among Candida spp. BSIs no resistance to caspofungin, amphotericin B, Voriconazole was noted. Candida tropicalis was the most common isolate, and 1 isolate of Candida glabrata showed dose-dependent sensitivity to fluconazole. Three out of 25 patients died of multi-drug resistant Gram-negative bacteria (12%) in 2013. Seventeen patients had radiological evidence of invasive fungal infections (no mortality was noted). CONCLUSIONS: Periodic review of infection-related data, as well as infection control practices, is essential to optimize clinical outcome in patients with pediatric malignancies. PMID- 26842143 TI - Unexplained splenic cyst in a patient with breast cancer after receiving Tian Xian Liquid. PMID- 26842144 TI - Bloodstream infections in pediatric patients at Cancer Institute, Chennai. AB - BACKGROUND: There is paucity of data on the epidemiology of bloodstream infections in pediatric cancer patients from India. Rationale use of antibiotics in febrile neutropenia is important for reducing morbidity and preventing the emergence of drug resistant bacteria. AIMS: The study was conducted to look at the prevalence of bloodstream bacterial infection and the antibiotic resistance profile at Cancer Institute, Chennai. SETTINGS AND DESIGN: This was a retrospective study. MATERIALS AND METHODS: Data on all blood cultures taken from pediatric cancer patients treated at Cancer Institute, Chennai, during the year 2013 were analyzed. The microbiological profile and sensitivity pattern were analyzed. RESULTS: A total of 1045 blood culture samples were taken, and there were 82/1045 (7.5%) positive blood cultures. Gram-negative organisms accounted for 50/82 (61%) of all positive cultures. Klebsiella pneumoniae (32%) was the most common Gram-negative isolate, and Staphylococcus aureus (93.5%) was the most common Gram-positive. There was high resistance to aminoglycosides and beta lactam/beta-lactamase inhibitor antibodies. CONCLUSION: Gram-negative organisms are the predominant bacteria isolated. There is high resistance to first-line combination antibiotics used as empiric therapy for treatment of febrile neutropenia. PMID- 26842145 TI - Epidemiology of bacterial isolates among pediatric cancer patients from a tertiary care oncology center in North India. AB - BACKGROUND: Infections are a major cause of morbidity and mortality in pediatric oncology. Resistance pattern of bacterial isolates determine empiric antibiotic therapy and influence outcome. AIMS: This study was planned to determine profile of bacterial isolates and their antibiotic resistance pattern among pediatric cancer patients. DESIGN: It was a retrospective, single institutional study. MATERIALS AND METHODS: The study was carried out in the department of pediatric hematology-oncology of a tertiary care cancer centre in north India over a period of 24 months (2012-2014). Microbiological data pertaining to pediatric cancer patients, less than 18 yrs of age was analysed. RESULTS: Hence, 238 bacterial isolates were cultured from among 1757 blood, urine and other specimens. Gram negative bacteria were the most common (74%) pathogens identified and E. coli and Klebsiella comprised 80% of them. A high incidence of extended spectrum beta lactamase producing organisms (84%), beta-lactam beta-lactamase inhibitor (78%) and carbapenem resistance was observed (29%). Blood stream infection with multi drug resistant Klebsiella was associated with high mortality. The gram positive bacteria isolated were predominantly staphylococcus aureus and were antibiotic sensitive. Reduction in the number of culture positive isolates in the second year of our study was probably due to rigorous implementation of infection control measures. CONCLUSION: These results on microbiologic profile and antibiotic sensitivity pattern of the isolates will be extremely helpful in revision of antibiotic guidelines for our patients and in developing strategies for coping with high prevalence of multi-drug resistance. Antibiotic stewardship and strict implementation of infection control practices will be important components of this effort. PMID- 26842146 TI - Multicentric synchronous ductal and mucinous carcinoma in ipsilateral breast: An unusual presentation. PMID- 26842147 TI - Review of spectrum and sensitivity of bacterial bloodstream isolates in children with malignancy: A retrospective analysis from a single center. AB - BACKGROUND: Febrile neutropenia is a life-threatening emergency in pediatric cancer patients. Its management is based on established guidelines that emphasize on prompt action. Consideration of local microbiologic spectrum and its susceptibility is pivotal in devising a rational protocol. AIMS: To study the spectrum of bacterial isolates and its antibiotic sensitivity profile in bloodstream infections (BSIs) of pediatric cancer patients. SETTINGS AND DESIGN: Retrospective study. MATERIALS AND METHODS: This study was conducted at a tertiary cancer center for pediatric cancer patients. Blood culture samples sent during the evaluation of patients with clinical diagnosis of febrile neutropenia during the year of 2013 were analyzed. The microbiological and antibiotic sensitivity patterns were studied. RESULTS: A total of 27 isolates represented BSIs out of 412 blood cultures sent (6.5%). These were predominantly Gram negative (92%) with Klebsiella contributing to the majority of them. Extended spectrum beta-lactamase production was seen in 59% of all isolates. Multidrug resistance phenotype was seen in 48%, extreme drug resistance in 32% and pan drug resistance in 16% of Gram-negative isolates. Klebsiella predominated in all of these isolates. Mortality resulted in 15% isolates, majorly contributed by Klebsiella. Colistin was the most sensitive antibiotic (75% sensitivity) and in significant number of cases the only salvage option. CONCLUSION: Gram-negative bacteria are the most common etiologic agents. The emergence of drug resistant strains of Klebsiella and the poor sensitivity of most of these strains to common first choice empiric agents is alarming. Low prevalence of Gram-positive organisms questions the routine use of empiric vancomycin. PMID- 26842148 TI - Rule-flouting by the Indian tobacco industry: A definite cause for concern. PMID- 26842149 TI - Invasive bacterial infections in a pediatric oncology unit in a tertiary care center. AB - BACKGROUND: Multidrug resistant (MDR) pathogens are becoming a major problem worldwide, more so in the immunocompromised hosts resulting in the urgent need of antibiotic stewardship. PURPOSE: To analyze the organisms isolated and the drug resistance pattern in a pediatric oncology unit. RESULTS: Data pertaining to infections with 128 positive cultures in patients with febrile neutropenia over a period of 1-year are presented. The unit antibiotic policy is decided depending on the sensitivity of the prevailing common organisms. We isolated Gram-negative organisms in 56% cases. Escherichia coli and Klebseilla were the most frequent lactose fermenting Gram-negative Bacilli and Pseudomonas and Acinetobacter the nonfermenting Gram-negative Bacilli. Only 20-30% of the Gram-negative organisms cultured were sensitive to a 3rd/4th generation cephalosporin. The combination of a beta-lactam/inhibitor covered 2/3rd of Gram-negative organisms. About 80% of the organisms were sensitive to carbapenems. There was no colistin resistance. About 44% of our cultures grew a Gram-positive bacterial organism and included coagulase negative Staphylococcus. We had an incidence of methicillin resistant Staphylococcus aureus to be 30%. About 30% of the enterococci isolated in our unit were vancomycin-resistant enterococci. About 23% of patients with a positive bacterial culture died. CONCLUSIONS: Infections in pediatric cancer patient's account for about 15-20% of the deaths in developing countries as these patients are at a high risk for developing MDR infections. Resistance rates among Gram positive and Gram-negative organisms have increased worldwide. Every unit needs a rational antibiotic policy. Antibiotic de-escalation and judicious decrease in the duration of antibiotics needs to be practiced. PMID- 26842151 TI - Reply to: Initial experience with hyperthermic intraperitoneal chemotherapy and cytoreductive surgery. PMID- 26842150 TI - Risk predictors for adverse outcome in pediatric febrile neutropenia: Single center experience from a low and middle-income country. AB - BACKGROUND: Risk stratification of patients with febrile neutropenia (FN) into those at "High Risk" and "Low Risk" of developing complications helps in making decisions regarding optimal treatment, such as whether to treat with oral or intravenous antibiotics, whether to treat as inpatient or outpatient and how long to treat. Risk predictors obtained from Western studies on pediatric FN are unlikely to be relevant to low middle-income country (LMICs). Our study aimed to identify clinical and laboratory parameters predictive of poor outcomes in children with chemotherapy-induced FN in a LMIC. PROCEDURE: Two hundred and fifty consecutive episodes of chemotherapy-induced FN in pediatric (<15 years) patients were analyzed prospectively. Adverse outcomes were defined as per SPOG 2003 FN study as serious medical complications (SMC) due to infection, microbiologically defined infection, and radiologically defined pneumonia (RDP). Variables found to be significant for adverse outcome (P < 0.05) on univariate analysis were selected for multivariate analysis. RESULTS: Five factors that were found to independently predict adverse outcome were (a) previously documented infection in the past 6 months, (b) presence of significant focus of infection, (c) absolute phagocyte count <100/mm3, (d) peak temperature more than 39 degrees C in this episode of FN, and (e) fever lasting more than 5 days during this episode of FN. CONCLUSIONS: Identifying the risk factors for adverse outcome in pediatric FN, which are objective and applicable across LMICs would contribute in developing guidelines for the management of FN in a resource-limited setting. PMID- 26842152 TI - Epidemiology of blood stream infections in pediatric patients at a Tertiary Care Cancer Centre. AB - BACKGROUND: Blood stream infections (BSI) are among the most common causes of preventable deaths in children with cancer in a developing country. Knowledge of its etiology as well as antibiotic sensitivity is essential not only for planning antimicrobial policy, but also the larger infection prevention and control measures. AIMS: To describe the etiology and sensitivity of BSI in the pediatric oncology unit at a tertiary cancer center. MATERIALS AND METHODS: All the samples representative of BSI sent from pediatric oncology unit during the period of January to December, 2013 were included in the study, and analyzed for microbiological spectrum with their antibiotic sensitivity. RESULTS: A total of 4198 samples were representative of BSI. The overall cultures positivity rate was 6.97% with higher positivity rate (10.28%) from central lines. Of the positive cultures, 208 (70.9%) were Gram-negative bacilli (GNB), 71 (24.2%) were Gram positive organisms, and 14 (4.7%) were Candida species. Lactose fermenting Enterobacteriaceae i.e., Escherichia coli (28.4%), Klebsiella pneumoniae (22.1%), and Enterobacter (4.8%) accounted for 55.3% of all GNB. Pseudomonas accounted for 53 (25.5%) and Acinetobacter 19 (9.1%) of GNB. Among Gram-positive isolates, staphylococci were the most frequent (47.8%), followed by Streptococcus pneumoniae 17 (23.9%), beta-hemolytic streptococci 11 (15.5%), and enterococci 9 (12.68%). Of GNB, 45.7% were pan-sensitive, 24% extended spectrum beta-lactamase (ESBL) producers, 27% were resistant to carbapenems, and 3.4% resistant to colistin. Pseudomonas was most sensitive, and Klebsiella was least sensitive of GNB. Of the staphylococcal isolates, 41.67% were methicillin-resistant Staphylococcus aureus (MRSA) and 10% of Coagulase Negative Stapylococci (CONS) were methicillin. CONCLUSION: A high degree of ESBL producers and carbapenem resistant Enterobacteriaceae is concerning; with emerging resistance to colistin, raising the fear of a return to the preantibiotic era. An urgent intervention including creating awareness and establishment of robust infection control and antibiotic stewardship program is the most important need of the hour. PMID- 26842154 TI - Primary yolk sac tumor of the endometrium: A rare entity. PMID- 26842153 TI - Alarming prevalence of community-acquired multidrug-resistant organisms colonization in children with cancer and implications for therapy: A prospective study. AB - BACKGROUND: Infection or colonization with multidrug-resistant organisms (MDRO) is associated with high mortality and morbidity. Knowledge of MDRO colonization may help in planning empirical antibiotic approach in neutropenic patients, which is known to improve patient outcomes. While routine cultures are positive and may help direct antibiotic therapy in only up to 15% neutropenic patients, surveillance cultures are positive in more than 90% of cancer patients. AIMS: To assess the rate of MDRO carrier status at presentation and rate of conversion to MDRO during the treatment. MATERIALS AND METHODS: Rectal swabs of all the outpatients presenting to pediatric oncology unit were sent within 7 days from date of registration from January 2014 to December 2014. Furthermore, stool cultures/rectal swabs of all patients who got directly admitted to the pediatric ward at presentation were sent within 24 h. Repeat rectal swabs were sent again for patients from this cohort when they got readmitted to the ward at least 15 days after last discharge or when clinically indicated. RESULTS: Baseline surveillance rectal swabs were sent for 618 patients, which included 528 children with hematological malignancies and 90 children with solid tumors. Forty-five (7.3%) showed no growth. Of the remaining 573, 197 (34.4%) patients were colonized by two organisms and 30 (5.2%) by three organisms. Three hundred and thirty-four (58.4%) showed extended spectrum beta-lactamase (ESBL) Enterobacteriaceae, of which 165 (49.5%) were ESBL sensitive to beta-lactam with beta-lactamase inhibitors combinations and 169 (50.5%) were resistant to combinations. One hundred and sixteen (20.2%) were carbapenem-resistant Enterobacteriaceae (CRE) and 65 (11.4%) had vancomycin-resistant enterococci in baseline cultures. Only 63 (21%) patients were colonized by a sensitive organism in their baseline surveillance cultures. Morbidity (Intensive Care Unit stay) and mortality was higher in patients colonized by MDR organisms. There was a significant correlation between the place of residence and CRE colonization status with the highest rate (60%) of CRE colonization observed in children from East India. The repeat cultures showed the further conversion of sensitive isolates to MDRO in 80% of these children, of which 40% each converted from non ESBL and non-CRE to ESBL and CRE, respectively. CONCLUSION: This is the first study illustrating the alarming high prevalence of community-acquired MDRO colonization, especially CRE, which has grave implications for therapy for children with cancer potentially compromising delivery of aggressive chemotherapy and affecting outcomes. This incidence further increases during the course of treatment. Knowing the baseline colonization also guides us for the planning of chemotherapy as well as antibiotic approach and infection control strategies. Local antibiotics stewardship including education of the healthcare workers as well as national level interventions to prevent antibiotic misuse in the community is critical to minimize this problem. PMID- 26842155 TI - Pattern of bloodstream infections in patients with hematological malignancies in a tertiary care centre. AB - BACKGROUND: The purpose of our study was to evaluate the clinical characteristics, to understand the pattern of bloodstream infections (BSIs), and to determine the risk factors contributing to high-risk febrile neutropenia in patients with hematological malignancy. MATERIALS AND METHODS: A comprehensive review of retrospective data was done from 2004 till 2012 from a single center. RESULTS: There were total 171 consecutive febrile episodes with 103 acute lymphoblastic leukemia (ALL) patients and 63 acute myeloid leukemia (AML) patients. The highest number of febrile neutropenia episodes occurred during ALL and AML induction followed by consolidation treatment with high-dose cytarabine. In our study population, the most common organisms isolated were Gram-positive (20%) followed by Gram-negative (6.4%) organisms. The incidence of fungal sepsis was only 3%. In our study, it was seen that the recovery from febrile neutropenia depends upon the disease, ALL recovered rapidly compared to AML (P < 0.001) and also the on the phase of treatment, i.e consolidation recovered earlier than induction (P < 0.001). There was no death recorded in this study population during febrile neutropenia. CONCLUSIONS: The incidence of febrile neutropenia depends upon the type of haematological malignancy and the aggressiveness of therapy required treating the disease especially during induction. The improvement in antimicrobial coverage and its prompt use leads to the selective growth of Gram-positive organisms. PMID- 26842156 TI - Penile cornu cutaneum with squamous cell carcinoma. PMID- 26842157 TI - Susceptibility profile of Gram-negative bacteremic isolates to beta lactam-beta lactamase inhibitor agents in comparison to other antibiotics. AB - BACKGROUND: Comprehensive understanding about the local antibiogram is an essential requirement for preparation of hospital or unit based antibiotic policy. Bacteremic isolates are the most useful ones for this purpose, representing invasive disease. OBJECTIVE: To analyze susceptibility pattern of bacteremic Gram-negative isolates in our center, to various antibiotics, including beta lactam-beta lactamase inhibitor (BL-BLI) agents and carbapenem. MATERIALS AND METHODS: This is a retrospective study done in Apollo Specialty Hospital, a tertiary care oncology center in South India. The susceptibility of Escherichia coli, Klebsiella, Acinetobacter and Pseudomonas blood culture isolates, identified between January 2013 and June 2014 to various antibiotics were analyzed. RESULTS: A total of 231-Gram-negative bacteremic isolates were analyzed. ESBL rate among E. coli isolates was 82.7% (67 out of 81) and 74.3% (58 out of 78) in Klebsiella. Carbapenem (imipenem) susceptibility rate in E. coli was 76.5%, Klebsiella 58.9%, Acinetobacter 32% and Pseudomonas 77.2%. Colistin susceptibility in E. coli was 96.2%, Klebsiella 93.5%, Acinetobacter 92.8% and Pseudomonas 97.7%. Difference in the susceptibility of Enterobacteriaceae to BL BLI agents (especially cefepime-tazobactam) and carbapenem were minimal. In nonfermenters, BL-BLI susceptibility was better than that of carbapenem. CONCLUSION: Findings of the study make a strong argument for using BL-BLI agents and sparing carbapenem to curtail the spiraling scenario of carbapenem resistance. PMID- 26842158 TI - Carcinoembryonic antigen levels in colorectal cancer: Are we too preoccupied? PMID- 26842159 TI - Clinical study of carbapenem sensitive and resistant Gram-negative bacteremia in neutropenic and nonneutropenic patients: The first series from India. AB - OBJECTIVE: Carbapenem resistance is a growing global concern. There is a lack of published clinical studies on the topic from Indian subcontinent. Aim of this study was to analyze clinical profile of patients with carbapenem sensitive and resistant bacteremia among neutropenic and nonneutropenic patients. MATERIALS AND METHODS: Retrospective analysis of 141 patients who had carbapenem resistant or sensitive Gram-negative bacteremia, identified over a period of 1-year was done by medical records review, in Apollo Specialty Hospital, a 300-bedded tertiary care Oncology, neurosurgical and orthopedic center in South India. RESULTS: Of the total 141 patients with Gram-negative bacteremia, 44 had carbapenem resistant ones. Of these 44 patients, 17 were neutropenics (resistant neutropenic group) and 27 nonneutropenic patients (resistant nonneutropenic group). Of the 97 patients with carbapenem sensitive bacteremia, 43 were neutropenic (sensitive neutropenic group) and 54 nonneutropenics (sensitive nonneutropenic group). The 28 days mortality was significantly higher in carbapenem resistant bacteremic group compared to the sensitive one (P = 0.008). CONCLUSION: This is the first study from India comparing clinical features of patients with carbapenem sensitive and resistant blood stream infections. Patients with carbapenem resistant bacteremia had higher mortality compared to patients with sensitive bacteremia. PMID- 26842160 TI - Frequency of bacterial isolates and pattern of antimicrobial resistance in patients with hematological malignancies: A snapshot from tertiary cancer center. AB - BACKGROUND: Infections are the most important cause of mortality in patients with high-risk febrile neutropenia. Emergence of multi-drug resistant organisms (MDROs) has become a major challenge for hemato-oncologists. Knowledge of the prevalent organisms and their antimicrobial sensitivity can help deciding the empirical therapy at individual centers and allows timely measures to reduce the risk of antimicrobial resistance. AIMS: To evaluate the frequency of bacterial isolates from all the samples and the pattern of bacterial bloodstream infections and incidence of MDROs. SETTINGS AND DESIGN: This is a retrospective analysis from a tertiary care cancer center. MATERIALS AND METHODS: From January to June 2014 information on all the samples received in Department of Microbiology was collected retrospectively. The data from samples collected from patients with hematological cancers were analyzed for types of bacterial isolates and antimicrobial sensitivity. RESULTS: A total of 739 isolates were identified with 67.9% of isolates being Gram-negative. The predominant Gram-negative organisms were Escherichia coli, Psuedomonas spp. and Klebsiella spp. Among the bacterial bloodstream infections, 66% were Gram-negative isolates. MDROs constituted 22% of all isolates in blood cultures. Incidence of resistant Gram-positive organisms was low in the present dataset (methicillin resistant Staphylococcus aureus and vancomycin-resistant enterococci-1.3%). CONCLUSIONS: The analysis reconfirms the Gram-negative organisms as the predominant pathogens in bacteremia seen in patients with hematological cancers. The high frequency of multi-drug resistance in the dataset calls for the need of emergency measures to curtail further development and propagation of resistant organisms. PMID- 26842161 TI - Esophageal cancer surgery: Concerns. PMID- 26842162 TI - Spectrum of malignancies in human immunodeficiency virus - positive patients at a Tertiary Care Centre in South India. AB - CONTEXT: India has a very large number of patients living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Opportunistic infections in these patients are commonly encountered. However, malignancies in such patients also do occur. AIM: The aim was to study the spectrum of malignancies in HIV-positive patients at a tertiary health care center. SETTINGS AND DESIGN: Retrospective study. MATERIALS AND METHODS: The cases were retrieved from pathology record files at our Institute from January 2003 to December 2008. The follow-up was obtained from Medical oncology records. The morphology of each case was reviewed along with immunohistochemistry wherever done. RESULTS: There were 61 such cases (51 males, 10 females). The age range was 7-78 years with a median of 35 years. The clinical presentation varied according to the malignancy. The largest group was non-Hodgkin lymphoma (18 nodal, 23 extra-nodal). The others included carcinoma breast (4), chronic myeloid leukemia (3), Burkitt Leukemia (2), squamous cell carcinoma anal region (2), multiple myeloma (2) and one each of miscellaneous malignancies (7). CONCLUSION: Malignancies in HIV positive individual occurred in younger individuals. Non-Hodgkin lymphomas, especially extra-nodal lymphomas, were the most common malignancy. There were no cases of proven Kaposi's sarcoma or invasive cervical carcinomas. There were two cases of multiple myeloma which are infrequently reported. PMID- 26842163 TI - Clinical and microbiological profile of febrile neutropenia in solid tumors and hematological malignancies at a tertiary cancer care center in South India. AB - BACKGROUND: Febrile neutropenia (FN) is a common but serious complication of chemotherapy in patients with solid tumors (ST) and hematological malignancies (HM). The epidemiology of FN keeps changing. OBJECTIVE: The objective was to study the epidemiology of FN in adult patients with ST and HM at Kidwai Memorial Institute of Oncology, Bangalore - A tertiary cancer care center. MATERIALS AND METHODS: Data of all episodes of FN that occurred during the period July 2011 to December 2011 were collected prospectively and analyzed. RESULTS: A total of 75 episodes of FN was observed during study period involving 55 patients. Febrile neutropenic episodes were more frequent in HM than in ST (57% vs. 43%). The rate of bloodstream infection was 14.7%. Gram-negative organisms were the predominant isolates (56.25%). Overall mortality rate was 13.3%. Presence of medical co morbidity and positive culture predicted high mortality. Mortality rate did not differ significantly between HM and ST (14% vs. 12.5%; P = 1.0). Gram-positive bacteremia was associated with greater mortality than Gram-negative bacteremia (P = 0.02). CONCLUSION: Empiric antibiotic treatment for FN should be tailored to the locally prevalent pathogens and their susceptibility patterns. PMID- 26842164 TI - Isolated central nervous system relapse in a patient with systemic diffuse large B-cell lymphoma: Diagnostic and treatment challenges. PMID- 26842165 TI - Basaloid squamous cell carcinoma of conjunctiva: A rare entity. PMID- 26842166 TI - Pattern of infection, therapy, outcome and risk stratification of patients with febrile neutropenia in a tertiary care oncology hospital in India. AB - CONTEXT: Indian febrile neutropenia (FN) data are limited, especially in adult solid tumor patients. AIMS: The aim was to study patterns of presentation, source of infection, management and outcome and to evaluate the factors which may correlate with outcome. MATERIALS AND METHODS: A retrospective analysis of prospective data of FN patients at a tertiary care oncology teaching hospital in India between 2007 and 2012. A standardized form was filled for each patient. Patient management was at the discretion of the treating physician. Multinational Association for Supportive Care in Cancer (MASCC) score was retrospectively calculated. Failure of therapy was defined as death, organ failure, shifting from outpatient to inpatient or requirement of intensive care support. SPSS version 16 was used for analysis. RESULTS: A total of 388 FN episodes were included: 256 in hematolymphoid and 132 in solid tumor patients. 156 episodes were high-risk by MASCC score. Focus of infection was clinical in 45% and radiologic in 16%. Blood cultures were positive in 18% cases, most commonly Gram-negative organisms (72%). 93% patients were treated with an antibiotic combination of third-generation cephalosporin/beta-lactamase inhibitor, with aminoglycoside or fluoroquinolone. Antibiotic sensitivity to ceftriaxone was low at 38% while sensitivity to cefoperazone/sulbactam and piperacillin/tazobactam ranged between 50% and 55% and for carbapenems 75%. Failure of therapy occurred in 156 episodes, most commonly due to the need for second line antibiotics. Mortality was 5.5%. On univariate analysis, MASCC score, age, type of malignancy, prophylactic growth factors, presence of focus of infection, hemoglobin and nadir platelet count correlated with FN complications. CONCLUSION: Gram-negative bacteremia continues to be the predominant cause of FN in our setup. PMID- 26842167 TI - Clinico-radiological profile with suspicion of lung cancer and its correlation with flexible TBNA (transbronchial needle aspiration) and cytological analysis initial results from a tertiary rural setup of Ambala District, Haryana. PMID- 26842168 TI - Extra nodal diffuse large B cell lymphoma at a rare site: A case report. PMID- 26842169 TI - Characterization and anti-microbial susceptibility of bacterial isolates: Experience from a tertiary care cancer center in Delhi. AB - BACKGROUND: Hospitalization for fever in cancer patients is associated with considerable morbidity, mortality, and cost. AIM: The aim of this study was to study the bacterial spectrum and susceptibility patterns of pathogens in culture positive patients from the oncology unit of our hospital. METHODS: We retrospectively reviewed the medical records of patients admitted in our cancer center (medical, radiation, and surgical oncology) from January to December 2013. Blood and respiratory secretions from the indoor patients were evaluated. RESULTS: Of the total 693 samples, 76.4% were Gram-negative and 23.6% were Gram positive. The most common bacterial isolates among Gram-negative organisms in blood were Escherichia coli, Salmonella and among the Gram-positive organism were Staphylococcus aureus and Enterococcus. Among the blood isolates extended spectrum of beta-lactamase, multidrug-resistant (carbapenem-resistant) and pan resistant bugs were seen in 47%, 15%, and 5% of the blood isolates. Among the Gram-positive organisms, 25% respiratory isolates were vancomycin-resistant Enterococci. CONCLUSION: We observed a high incidence of Gram-negative isolates with clinically significant resistance to first-line antibiotics such as cephalosporin's, piperacillin tazobactum, and fluoroquinolones. PMID- 26842170 TI - Patient with multiple metachronous primary cancers. PMID- 26842171 TI - Factors predicting outcome in high risk febrile neutropenia in patients receiving intensive chemotherapy for acute sleukemia: A prospective, observational study from South India. AB - BACKGROUND: Outcome of febrile neutropenia (FN) in acute leukemia patients undergoing intensive chemotherapy from India is scanty. MATERIALS AND METHODS: A prospective, observational, single institutional study was conducted to evaluate the clinical features, microbiological aspects, risk factors influencing the outcome of high risk FN during intensive therapy in acute leukemia. RESULTS: Among 115 febrile episodes, though 94 (81.7%) had indwelling central venous catheter (CVC) at the time of diagnosis of FN, infective foci clinically were identified in 70.4% of episodes, with lung as the major site (25.2%) followed by CVC (17.4%). Microbiological documentation was possible in 33% (n = 40) episodes. Gram-negative bacteria isolates were 58.3% and Gram-positive isolates were 41.7% of which Pseudomonas was the predominant Gram-negative and Staphylococcus aureus was the most common Gram-positive isolate. Piperacillin-tazobactam + amikacin were used as first line antibiotic in 93% episodes and second line antibiotics were necessary in 73% episodes. Granulocyte colony stimulating factor was used in 60.9% episodes of high risk FN mostly in acute myeloid leukemia consolidation patients. Eighteen episodes (15.7%) were assigned to have invasive fungal disease. Eleven (9.6%) out of 115 high risk FN had a fatal outcome. Presence of pulmonary infection predicted for fatal outcome (P = 0.02). CONCLUSION: This study reports the outcome of high risk FN in patients with acute leukemia undergoing intensive chemotherapy. Gram-negative isolates are highly sensitive to piperacillin-tazobactum and hence in a cost restraint scenario, carbapenems needs to be judiciously used. Focus of Infection in lungs during FN predicted higher fatal outcomes. PMID- 26842172 TI - Prevalence of abnormal mammogram among working Thai women. PMID- 26842173 TI - An audit of febrile neutropenia cases from a rural cancer center in India. AB - BACKGROUND: Data of febrile neutropenia (FN) from rural cancer centers is sparse. We did a audit of outcome of patients with FN in the period of March 2013-August 2013. The aim was to help us to develop rational antibiotic usage policies. MATERIALS AND METHODS: Retrospective analysis of all consecutive patients presenting with FN. Data regarding demographic profile, tumor type, intent of treatment, chemotherapy regimen, blood culture susceptibility details, use of antibiotics, response to antibiotics and complications of FN were noted. SPSS (Statistical Product and Service Solutions) 16 was used for analysis. RESULTS: 67 patients had FN and there were 91 episodes. The median day of presentation with FN after start of chemotherapy was 10 days. The nadir absolute neutrophil count was 161.5 and nadir platelet count 1,00,000. The median multinational association for supportive care in cancer (MASCC) Score was 24. In accordance with MASCC there were 27 high risk FN and 64 low risk FN episodes. On multivariate analysis using logistic regression MASCC score strata was the only significant variable that predicted failure to 1st line antibiotics (P = 0.03) and mortality (P = 0.01). Nine patients (9.9%) had positive isolates on blood cultures. The blood culture isolates were predominantly Gram negative (66.7%). CONCLUSION: The importance of developing local guidelines for rational antibiotic usage is highlighted. PMID- 26842174 TI - Management of febrile neutropenia in malignancy using the MASCC score and other factors: Feasibility and safety in routine clinical practice. AB - BACKGROUND: The current standards for empirical broad-spectrum intravenous antibiotic (AB) treatment, combined with hospitalization, are cautious and safe, but lead to over-treatment of a substantial group of patients. We need to validate parameters to identify these low-risk febrile-neutropenia (FN) patients, who could then be safely treated in an outpatient setting with minimal/no AB treatment. MATERIALS AND METHODS: A retrospective analysis for validation of a risk-assessment model in FN patients was done on a patient population from January 2007 to December 2008. Inclusion criteria were a histological diagnosis of malignancy, FN secondary to chemotherapy, absolute-neutrophil-count of <= 500/MUl, axillary temperature of >= 38 degrees C, and age >= 14 years. Other clinical and laboratory parameters were explored for risk stratification during the FN episodes. Receiver-operating characteristic curves were used to find the threshold value, an Chi-square analysis was done to find the association between the outcome and the parameters. RESULTS: A total of 178 FN episodes were documented; 22 in solid tumors and 156 in hematolymphoid malignancies. Culture positivity was documented in 59 episodes; peripheral blood was the most common source, with Escherichia coli being the most common organism identified. Risk stratification was done using the Multinational Association of Supportive Care in Cancer (MASCC) risk-index score. The association between the MASCC score and risk stratification could not be established (P = not significant) at a score of <= 21; however, it was found to be significant at a score of <= 18. The total number of complications was 23 (sepsis 22, mortality 23). Other factors found to be significantly associated with a high risk of complications in the univariate analysis were, mucositis (P = 0.03), maximum temperature >= 103 degrees F (P = 0.01), tachycardia (P < 0.001), tachypnea (P = <0.001), age (P = 0.006), high dose of steroid (P < 0.001), total duration of fever (>= 2.5 days (for which sensitivity (S) and specificity (Sp) were 87 and 81%, respectively), serum creatinine (>= 0.45 mg%, S = 100%, Sp = 97%), serum-bilirubin (>= 0.5 mg/dl, S = 100%. Sp = 90%), requirement of second-line antibiotics (P = 0.02), intensive care (P <= 0.001), ventilatory support (P < 0.001), and requirement of packed cell (PC) transfusion (P = 0.02). In the multivariate analysis, mucositis (P = 0.02), HD steroid use (P = 0.026), and PC requirement (0.026) were identified as independent variables. CONCLUSIONS: The MASCC risk-index score was found to be meaningful at a score of <= 18. Other clinical and laboratory parameters were found to have a strong association with risk stratification in cancer patients during FN episodes. PMID- 26842175 TI - Multidisciplinary team meetings for optimal management of cancer patients: A must? PMID- 26842176 TI - Comparison of isolates and antibiotic sensitivity pattern in pediatric and adult cancer patients; is it different? AB - BACKGROUND: Infection is a common cause of mortality and morbidity in cancer patients. Organisms are becoming resistant to antibiotics; age appears to be one of the factors responsible. We analyzed common organisms and their antibiotic sensitivity pattern in the correlation with age. METHODS: This is a single institutional, retrospective analysis of all culture positive adult and pediatric cancer patients from January 2007 to December 2007. For statistical analysis, Chi square test for trend was used and P values were obtained. Of 1251 isolates, 262 were from children <12 years of age and 989 were from adolescents and adults (>12 years of age). Gram-negative organisms were predominant (64.95) while Gram positive constituted 35.09% of isolates. RESULTS: The most common source in all age groups was peripheral-blood, accounting to 47.8% of all samples. The most common organisms in adults were Pseudomonas aeruginosa (15.3%) while in children it was coagulase negative Staphylococcus aureus (19.8%). Antibiotic sensitivity was different in both groups. In pediatric group higher sensitivity was seen for Cefoparazone-sulbactum, Cefipime, Amikacin, and Tobramycin. No resistance was found for Linezolid. CONCLUSIONS: The isolates in both children and adults were predominantly Gram-negative though children had proportionately higher Gram positive organisms. High-dose cytarabine use, cotrimoxazole prophylaxis, and frequent use of central lines in children especially in hematological malignancies could explain this observation. Children harbor less antibiotic resistance than adults; Uncontrolled, cumulative exposure to antibiotics in our community with increasing age, age-related immune factors and variable bacterial flora in different wards might explain the higher antibiotic resistance in adults. Thus age is an important factor to be considered while deciding empirical antibiotic therapy. PMID- 26842177 TI - Overexpression of cyclin A in oral dysplasia: An international comparison and literature review. AB - Oral squamous cell carcinoma (OSCC) is one of the most debilitating cancers in the world and while its causes have been heavily researched, the outcome remains grim. Most of these cancers are identified in the late stage and as a result treatment options are limited. Therefore, researchers have focused their efforts on recognizing and identifying dysplastic tissue that has an increased chance of progressing to cancer. Research has begun to look at cell cycle dysfunctions and in particular, aberrant protein functions as a way of identifying the cellular mechanism at fault. The overexpression of a group of regulatory proteins called cyclins has been demonstrated in many types of dysplasia and carcinomas. Although researchers have identified several different types of cyclins as potential culprits, we chose to focus our study primarily on the overexpression of cyclin A. While most research on oral dysplasia and OSCC has been focused on cyclin D, studies have been done on cyclin A. While the etiology of oral dysplasia/SCC appears to be multifactorial, we chose to compare our results with those of similar studies performed across the globe. The social factors, such as the increased use of tobacco that may have contributed to our results, were compared with similar studies performed in Europe and Asia. While our results were remarkably similar and demonstrated a link between the overexpression of cyclin A in oral dysplasia, there exists some differences and thus may require a multicenter, longitudinal study. PMID- 26842178 TI - Fibromatosis of the ovary. PMID- 26842179 TI - Unique roles of nanotechnology in medicine and cancer. AB - Here we review the scope of nanotechnology in Medicine and human cancer. The imaging and therapy agents can be co-delivered by same nanoparticle for integrated molecular diagnosis, therapy, and follow-up of cancer or 'cancer theranostics' is implying multimodal use of nanoparticles in cancer care. Nanoparticles are used for passive targeting and in conjugation with ligands for active targeting, to have optimum concentrations of imaging and therapeutic agents in the tumor cells specifically, sparing normal tissue from unwanted side effects. Potential utility of nanoparticles in the nano biosensors, nano fluorescent tag imaging, nano tumor mapping, nano gene profiling, nano molecular delivery, nano chemo-radio therapy, nano thermotherapy, nano photodynamic therapy, etc., is tending to revolutionize medicine particularly personalized cancer care and laboratory. Nanoparticle induced oxidative stress based inflammation reported by few studies; in lung, liver and brain required further investigations. PMID- 26842180 TI - A case of biphasic pulmonary blastoma showing good response to preoperative chemotherapy. PMID- 26842181 TI - Association of vascular endothelial growth factor single nucleotide polymorphisms on the prognosis of breast cancer patients. AB - BACKGROUND: Vascular endothelial growth factor (VEGF), a major mediator of vascular permeability and angiogenesis, may play a pivotal role in mediating the development and progression of breast cancer. In the present study, we examined the genetic variations of the VEGF gene to assess its possible relation to breast cancer. MATERIALS AND METHODS: A total of 200 patients with histologically confirmed cases of breast cancer and 200 healthy women were genotyped for VEGF single nucleotide polymorphisms (405G > C and -1154G > A) by polymerase chain reaction-restriction fragment length polymorphism analysis. Pre-operative plasma VEGF levels were determined by enzyme-linked immunosorbent assay in 200 women with breast cancer and in 200 normal female controls. RESULTS: The genotype frequencies of the +405G > C, -1154G > A polymorphisms did not show a significant deviation from the Hardy-Weinberg expectation. The minor allele frequencies of the +405G > C and -1154G > A polymorphisms among cases and controls were 33.5% (C allele), 31.5% (A allele) and 35% (C allele), 34.5% (A allele) respectively. +405GG and -1154GG genotypes were associated with higher levels of VEGF among breast cancer cases and controls. Increased plasma VEGF levels were significantly associated with, clinical stage of the disease (P = 0.035). CONCLUSION: Although none of the polymorphisms were significantly associated with breast cancer, some of the VEGF genotypes may influence tumor growth through an altered expression of VEGF and tumor angiogenesis. PMID- 26842182 TI - Xanthohumol inhibits cellular proliferation in a breast cancer cell line (MDA MB231) through an intrinsic mitochondrial-dependent pathway. AB - AIMS: Xanthohumol isolated from hops has been reported to exhibit anticancer effects in diverse human cancers. However, its effect on breast cancer has not yet been clearly defined. The purpose of this study was to investigate the effects of xanthohumol on breast cancer cell proliferation. MATERIALS AND METHODS: After treatment with 5 MUM, 10 MUM, and 20 MUM xanthohumol for 48 h, cells from the human breast cancer cell line MDA-MB-231 were studied using colony assay, flow cytometry, and western blotting. RESULTS: The survival rate of the MDA-MB231 cells treated with 10 MUM and 20 MUM xanthohumol for 48 h decreased significantly by 64.7 +/- 1.8% and 40.1 +/- 1.8%, respectively. The numbers of SubG0/G1 cells in the group treated with 10 MUM and 20 MUM xanthohumol increased significantly to 11.3 +/- 0.2 and 18.4 +/- 0.1, respectively. A ladder pattern of DNA fragmentation was also observed. Xanthohumol increased the expression of Bax in the mitochondria, which correspondingly decreased in the cytoplasm. The activity of caspase-3 and caspase-9 was shown to increase significantly in the treated groups but not in the control group. CONCLUSIONS: Xanthohumol inhibited the proliferation of MDA-MB-231 cells through a mitochondria- and caspase dependent apoptotic pathway. This result suggests that xanthohumol might serve as a novel therapeutic drug for breast cancer. PMID- 26842183 TI - Direct oral microscopy to enhance diagnostic accuracy. PMID- 26842185 TI - Primary ovarian carcinoid tumor simulating virilizing tumor of the ovary: A rare entity. PMID- 26842184 TI - Role of Sphk1 in the malignant transformation of breast epithelial cells and breast cancer progression. AB - BACKGROUND: The ojective of the following study is to investigate the role of sphingosine kinase 1 (Sphk1) in the malignant transformation of breast epithelial cells and breast cancer progression and its mechanism. MATERIALS AND METHODS: Immunohistochemistry was performed to detect Sphk1 and E-cadherin (E-cad) in resected breast samples. Sphk1 was transfected in normal human breast epithelial cell line (MCF-10A) by Lentivirus and silenced in breast cancer cell line (MCF-7) using small interfering ribonucleic acid. The effect of tumor necrosis factor alpha (TNF-alpha) and/or N, N-dimethylsphingosine (DMS) on the Sphk1 and E-cad expression, MCF-10A cell proliferation and invasion was investigated. Real time polymerase chain reaction and western-blot was used to detect messenger ribonucleic acid and protein. Cell counting kit-8 and transwell were used to measure cell proliferation and invasion. RESULTS: Sphk1 was positive expression in 114 breast tumors (75.50%) but negative in fibroadenomas. The expression of E cad and Sphk1 were negatively correlated and E-cad (-)/Sphk1 (+) carriers showed higher ratio of axillary lymph node metastasis than E-cad (+)/Sphk1 (-) carriers. Overexpression of Sphk1 in MCF-10A reduced E-cad expression and improved cell proliferation and invasion, but knockdown of Sphk1 in MCF-7 decreased cell proliferation and invasion. TNF-alpha increased Sphk1 expression, enhanced the ability of Sphk1 in decreasing E-cad expression, which could be blocked by DMS. TNF-alpha promoted MCF-10A cell proliferation and invasion. CONCLUSION: Sphk1 plays an important role in the malignant transformation of breast epithelial cells and modulates breast cancer metastasis through the regulation of E-cad expression. TNF-alpha can up-regulate Sphk1 expression and reduce E-cad expression through Sphk1, which can be blocked by DMS. TNF-alpha/Sphk1/E-cad pathway may be a newly discovered pathway and plays an important role in tumorigenesis and metastasis. PMID- 26842186 TI - Prevalence of KRAS mutations in metastatic colorectal cancer: A retrospective observational study from India. AB - BACKGROUND: One of the genetic alterations implicated in tumor progression in colorectal cancers (CRCs) are abnormalities in Kristen Rat Sarcoma (KRAS) gene. Evaluation of KRAS mutation status is an important prognostic factor and has predictive value in deciding first line therapy based on monoclonal antibodies such as Cetuximab and Panitumumab in metastatic CRCs. MATERIALS AND METHODS: In this retrospective study, we analyzed 7 different somatic mutations in Exon 2 of KRAS gene in 299 unselected incidental CRC patients who visited the hospital for clinical management during the period 2009-2013. Most of the tumors were primarily originating from colon and rectum; nevertheless, there were a few from rectosigmoid, sigmoid, ceacum and anal canal in the study group. Genomic DNA extracted from paraffin embedded tumor tissues was screened for 7 point mutations located in Codons 12 and 13 of KRAS gene, using Scorpions amplified refractory mutation system real time polymerase chain reaction technology. Statistical analysis was performed to assess bivariate relationship between different variables that includes: mutation status, mutation type, tumor location, tumor morphology, age and sex. RESULTS: Prevalence of mutation in Codons 12 and 13 was 42.8% in the study group. Well-differentiated tumors had significantly more mutation positivity than moderately and poorly differentiated tumors (P = 0.001). 92% of the mutations were from Codon 12 and 8% in Codon 13. Glycine to Arginine was relatively more common in rectosigmoid followed by ceacum, while Glycine to Alanine mutation was relatively more prevalent in sigmoid, followed by rectum and rectosigmoid. CONCLUSION: The results suggest a prevalence of KRAS mutation at 42.8% in Indian population indicating that this testing is very crucial for targeted therapy management in metastatic CRC in India. Further analysis on mutation status of other homologues such as NRAS and downstream partner, v-raf murine sarcoma viral oncogene homolog B1, would add value to understanding the role of anti-epidermal growth factor receptor therapy in CRC management. PMID- 26842187 TI - L-asparaginase induced acute parotitis during intensification therapy of acute lymphoblastic leukemia. PMID- 26842188 TI - The impact of hereditary colorectal cancer on the Indian population. AB - INTRODUTION: The incidence of colorectal cancer in India is lower compared to the Western world. In Western countries, most cases of colorectal cancer are sporadic and the hereditary variety accounts for only 10-15% of all cases. The aim of the present review is to determine the clinical and epidemiological characteristics of hereditary colorectal cancer in India. MATERIALS AND METHODS: A Medline search was conducted to review the literature published from India regarding colorectal cancer. The keywords used included India, colorectal cancer, hereditary nonpolyposis, and familial adenomatous polyposis. All relevant articles were reviewed and the characteristic features of this disease in Indian population were collated and presented. RESULTS: Literature search revealed eighty two articles pertinent to India, of which only ten articles had relevant information on hereditary cancers. Although the overall incidence of colorectal cancer was low in both genders, there were a high proportion of patients developing colorectal cancer before the age of 45 years. Additionally, there was a higher proportion (10-15%) of hereditary nonpolyposis colorectal cancer cases, as confirmed by microsatellite instability. CONCLUSION: The overall incidence of colorectal cancer is low in India. There is a tendency to affect a relatively younger age group, and we infer that the incidence of hereditary colorectal cancer is high and is similar to the Western countries. PMID- 26842189 TI - Giant inflammatory fibroid polyp of the terminal ileum presenting with lower urinary tract symptoms: Case report. PMID- 26842190 TI - Comparison of different scoring systems in patients undergoing colorectal cancer surgery for predicting mortality and morbidity. AB - BACKGROUND: Preoperative risk estimation evaluating mortality and morbidity might help surgical decision. AIMS: The aim of this study was to compare the sensitivities of physiologic and operative severity score for the enumeration of mortality and morbidity (POSSUM), portsmouth-POSSUM (P-POSSUM), colorectal-POSSUM (CR-POSSUM), the Association of Coloproctology of Great Britain and Ireland colorectal cancer model (ACPGBI CRC) and revised ACPGBI CRC scoring systems that are used for evaluating mortality and morbidity in colorectal surgery performed in third-level healthcare centers. SETTINGS AND DESIGN: A retrospective analysis has been performed on 335 consecutive patients undergoing colorectal cancer surgery between 2002 and 2012. MATERIALS AND METHODS: Mortality and morbidity risks of 335 patients who underwent colorectal cancer were evaluated using these scoring systems and the results were compared with actual mortality and morbidity within postoperative 30-day that extend the duration of hospital stay. STATISTICAL ANALYSIS USED: The receiver operating characteristic (ROC) curves were designed to identify the score values. RESULTS: Results of POSSUM and P POSSUM systems showed statistical differences compared with those of CR-POSSUM, ACPGBI CRC and revised ACPGBI CRC systems (P < 0.05). P-POSSUM was found to be the best scoring system for predicting mortality risk, although all scoring systems seem to be appropriate for this parameter. On the other hand POSSUM, which can predict morbidity, was found to have moderate differentiation ability due to the magnitude of the area under the ROC curve. CONCLUSIONS: Despite altering patient demographics and surgical conditions, POSSUM seems to lead as the best scoring system for predicting mortality and morbidity among others including those most-recently proposed. PMID- 26842191 TI - Liposarcoma of thyroid gland: A review of the gained experience. PMID- 26842192 TI - Predictors of quality of life in patients with colorectal cancer in Iran. AB - BACKGROUND: Colorectal cancer (CRC) is one of the most common invasive cancers and is responsible for physical and psychosocial morbidity. Quality of life (QOL) is an important outcome for these patients. The aim of this study was to determine the predictive factors of QOL in patients with CRC. MATERIALS AND METHODS: A cross-sectional design was used to assess 110 patients with CRC who referred to Oncology Department of Razi Hospital, Guilan. Data were collected by structured interview with patients and review of medical records. Generic and specific QOL were evaluated by short form-36 and functional assessment of cancer therapy-colorectal, respectively. Generalized linear models identified variables significantly associated with QOL. RESULTS: Out of 110 patients with CRC, 58.2% were men. Mean age of patients was 58.33 +/- 12.39 years. Mean of Generic and specific QOL were 70.92 +/- 15.56 and 95.72 +/- 19.18, respectively. In regression analysis, age, sex, living condition, health insurance, hospitalization frequency, Karnofsky performance status, and co-morbidity were predictors of generic QOL and age, sex, living condition, health insurance, monthly income, family history of CRC, Karnofsky performance status, and co morbidity were predictors of specific QOL in patients. CONCLUSION: There are nine socio-demographic and clinical factors that are significant predictors of QOL in patients with CRC which should be considered in treatment and care of patients. The findings of this study should be the target of future research, emphasizing the need for interventional studies that minimize the adverse impact of the disease symptoms on the QOL in patients with CRC. PMID- 26842193 TI - Response to article - Mohanty NK, Kumar A, Vasudeva P, Jain M, Prakash S, Arora RP. Analysis of the perioperative and five-year oncological outcome of two hundred cases of open radical cystectomy: A single center experience. Indian J Cancer 2012;49 (1):96-101. PMID- 26842194 TI - Colorectal carcinoma up to the second decade of life: An 8-year experience in a tertiary care center. AB - AIMS AND OBJECTIVES: To evaluate the demographic pattern, incidence, and histological characteristics of colorectal carcinomas (CRCs) in very young adults diagnosed in the center. MATERIALS AND METHODS: We retrieved and reviewed slides and data pertaining to all the cases of CRCs and "segregated into decade wise age groups" from the archives of Department of Pathology. Patients with age <=20 years diagnosed during the last 8 years (2006-2013) were further evaluated. RESULTS: Totally, 590 cases of CRCs diagnosed over last 8-year period, of which 4.2% (25 cases) presented in the study group (age <=20 years) with a mean age of 17 years. About 50% of the tumors were either signet ring cell, mucin-secreting or poorly differentiated carcinomas. Four cases occurred in a background of familial adenomatous polyposis (FAP), three of which showed high-grade dysplasia, while in one case, carcinoma-in-situ was diagnosed. In all but two cases, rectum was the site of involvement except FAP cases in which colorectal location was noted. CRCs show a sharp rise in earlier age onset (<=40 years) and an increasing trend was followed in patients between age groups third, fourth, and fifth decades of life over the last 8 years. CONCLUSION: Colorectal carcinomas show an increasing trend in young age (<=40 years). This change may be attributed to dietary, lifestyle changes, and newer genetic alterations in developing countries. In very young age group (<=20 years), a higher grade and stage at the time of diagnosis and predominantly rectal involvements are the distinct features. PMID- 26842195 TI - Colonic J pouch neo-rectum versus straight anastomosis for low rectal cancers. AB - AIM: The development of sphincter saving procedures for low carcinoma rectum has been the consequence of oncological and technological factors. The major disadvantage associated with these procedures is the development of anterior resection syndrome because of the resection of rectal reservoir. Colonic J pouch (CJP) neorectum has been practiced as an antidote to overcome this problem. We are working at a tertiary care center, which is a high volume center for rectal cancers. We thought it worthwhile to assess the efficacy of J Pouch neorectum viz.-a-viz. a straight coloanal anastomosis for low rectal cancers. MATERIALS AND METHODS: Hospital based prospective randomized study (June 2007-December 2009) low rectal cancers (4-12 cm from the anal verge). One group (20 patients) subjected to low/ultralow anterior resection with straight anastomosis (SA) and other group (22 patients) to CJP. The two groups were compared on the basis of functional outcome. RESULTS: Anastomotic leak, strictures, frequency of bowel movements, nocturnal bowel movements, use of retarding medication and incontinence to solids, liquids and gases were seen more in SA group. All these findings were statistically significant. CONCLUSIONS: We conclude that CJP has a significant functional advantage over SA and improves the overall quality-of-life in patients of low rectal cancers and the advantage persisted over a period of more than 30 months. PMID- 26842196 TI - Ewing's sarcoma of the mandibular condyle. PMID- 26842197 TI - Young onset colorectal cancer: How does it differ from its older counterpart? AB - BACKGROUND: Colorectal cancer in the young has been a debated topic in literature with conflicting reports as to its pattern of occurrence and survival as compared to the older age group. MATERIALS AND METHODS: Retrospective study to analyze the clinicopathological characteristics, treatment modalities and survival of sporadic young-onset colorectal cancer (YOCR) patients (<40 years) and compare them with the older group (>40 years). RESULTS: Of 172 patients managed, 72 (42%) were in the YOCR group. Among 72 patients, six were excluded because of hereditary syndromes. Incontinence (P = 0.02) and obstruction at time of presentation (P = 0.03) was significantly more common in the YOCR group. Left sided disease was more common in YOCR group (47/66) compared to the older group (65/100), but the difference was not statistically significant (P = 0.45). The proportion of rectal cancers was significantly more in the YOCR group (39/47) compared to the older group (39/65) (P = 0.01). Significant difference in resectability was noted in the left sided (YOCR 26/47 vs. older 49/65 P = 0.04) and the rectal cancers (YOCR 18/39 vs. Older 29/39 P = 0.02). The survival was similar among the two groups. CONCLUSIONS: Sporadic colorectal cancers in the young are more advanced and less resectable when compared to older population. Genetic studies are needed to elaborate the reasons for left sided predominance and aggressiveness of sporadic colorectal cancers in the younger subgroups. PMID- 26842198 TI - Pilomatrix carcinoma of the eyelid. PMID- 26842199 TI - Reproductive factors and risk of breast cancer: A Review. AB - Breast cancer is one of the most common incident cancer and cause of death from cancer in women. It is known that several factors that influence hormonal status (e.g., age at first child birth) or are markers of change in hormonal status (e.g., age at menarche and age at menopause) are associated with the risk of breast cancer. Reproductive factors are known risk factors for breast cancer that probably act early in life. They point toward endogenous estrogens as likely player in the initiation, progression, and promotion of breast cancer. An attempt has been made in this article to review the scientific data published in Indexed journals on the role of reproductive factors in breast cancer. PMID- 26842200 TI - Pure micropapillary carcinoma of breast: A quite rare subtype. PMID- 26842201 TI - Garlic: Review of literature. AB - Garlic is one of the components, which have effects on reducing the risk of cancer. Including garlic in the diet helps for the betterment of the health. Medicinal effects of the garlic were known since 5,000 years. Recently, studies were carried out to known its effect on the cancer cell lines. Many studies have shown its effects not only on carcinomas, but also on the cardiovascular system and immune system. Functions of the each component of the garlic were studied to know exactly, which component has got beneficial effect. So this review has been carried out to know about the component, functions of each component, mode of action, and beneficial effects of the garlic. PMID- 26842202 TI - Nimotuzumab as a palliative treatment for liver metastasis: The first world report. PMID- 26842203 TI - The outcome effect of double-hormonal therapy in premenopausal breast cancer patients with high nodal-status: Result of a prospective randomized trial. AB - PURPOSE: The combination of taxanes and anthracyclines has proven efficacy in node-positive (N+) premenopausal primary breast cancer patients. Ovarian ablation is also associated with better survival outcomes in premenopausal hormone receptor positive (HR+) patients. Therefore, this trial aims to determine the superiority of combined hormonal treatment of ovarian ablation with tamoxifen (TMX) versus TMX alone, in premenopausal N+, HR + patients receiving adjuvant chemotherapy (AC) with taxane and anthracycline. MATERIALS AND METHODS: Premenopausal women who had surgically removed breast cancer with histologically confirmed N + and HR+ were included in the trial. The AC consisted of six cycles of taxotere, adriamycin, cytoxan or taxotere, epirubicin and cytoxan with the completion of radiation therapy. Patients were randomly assigned to receive TMX 20 mg/day for 5 years or up to menopause or TMX 20 mg/day for 5 years plus goserelin (GOS) 3.6 mg injection per month for 2 years. The primary end point was disease-free survival (DFS). RESULTS: Between 2003 and 2011, 101 consecutive patients were allocated to TMX (51 patients) and TMX/GOS (50 patients) groups. The mean follow-up period was 52.4 +/- 2.8 months. DFS was 43.0 +/- 3.6 months versus 49.9 +/- 4.22 months (P = 0.13) and overall survival was 51.1 +/- 3.8 months versus 53.1 +/- 4.2 months (P = 0.50) in the TMX and TMX/GOS groups, respectively. The results showed 9% absolute risk reduction with respect to DFS in favor of the TMX/GOS group. CONCLUSION: This study group was comprised of stage II and III disease patients with high nodal status. The TMX/GOS combination reduced absolute risk of developing first locoregional or distant relapse by almost 9%. Longer follow-up is required to justify this protocol for routine use. PMID- 26842204 TI - Isolated splenic vein thrombosis and splenic infarct due to external compression of enlarged lymph nodes in a patient with lymphoma. PMID- 26842205 TI - An analysis of response to neo-adjuvant chemotherapy in patients with locally advanced breast cancer with emphasis on pathological complete response. AB - CONTEXT: In India, most breast cancer women present at a locally advanced stage. Routine practice in majority of the cancer centers is to administer neo-adjuvant chemotherapy (NACT) followed by loco-regional treatment. Surgery is scheduled after 3 or 4 cycles. The patients who achieve pathological complete response (pCR) are expected do well. AIMS: The present study was conducted to analyze our results with NACT, to know pCR rate, to compare pCR rates among various subgroups and to determine the factors which predict pCR. SETTINGS AND DESIGN: The study was conducted in a tertiary care university affiliated cancer hospital in South India. SUBJECTS AND METHODS: All patients with non-metastatic locally advanced breast cancer and agreed by the hospital tumor board to receive NACT were included. At each visit, response was assessed according to RECIST criteria. Re staging work up and mammography was done prior to surgery. STATISTICAL ANALYSIS USED: Chi square test was used to analyze categorical variables and uni and multivariate analysis were performed to determine the factors predicting pCR rates. RESULTS: A total of 84 patients received NACT. Median age was 46 years (ranged from 28 to 66), 46 patients were premenopausal. Totally 72 patients completed the full course before surgery. Clinical response was complete in 26, partial in 52 and 3 had local progression, one stable and two patient developed distant metastasis. Forty-eight patients underwent modified radical mastectomy and breast could be conserved in 34 patients, pCR rate was 36%. CONCLUSIONS: Compared with historical controls particularly from India, we could achieve higher pCR rates. PMID- 26842206 TI - Giant ameloblastoma: A rarity. PMID- 26842208 TI - Acute leukemia presenting as primary ecthyma gangrenosum. PMID- 26842207 TI - Retrospective analysis of clinicopathological factors and outcome in breast cancer in young women in a tertiary care hospital in India. AB - BACKGROUND: The proportion of breast cancer is rising in India. It presents at a younger age in India as compared to the western countries. AIMS: This is a retrospective study of 86 breast cancer patients less than 40 years treated in a single center from June 2006 to June 2011. The aim was to assess the factors that may influence clinical outcome. MATERIALS AND METHODS: Data were collected from medical records. Variables such as age, stage, surgery, chemotherapy, tumor size, grade, nodal status, perinodal extension, lymphovascular emboli, estrogen receptor, progesterone receptor, and HER-2 neu were analyzed in relation to outcome. RESULTS: Out of total 613 breast cancer patients, 91 (14.8%) were younger than 40 years. Five were excluded due to incomplete data; hence, 86 patients were included in this study. Median tumor size was 3 cm and lymph node positivity was 56.9%. Lymphovascular emboli were positive in 48.8% and perinodal extension was positive in 41.8%. Estrogen receptor positivity was 34.8%, progesterone receptor positivity was 45.3%, and triple negativity was 45.3%. The median follow-up period was 27 months with disease free survival being 73.2% and overall survival being 87.2%. In univariate analysis, the factors significantly associated with survival were stage at presentation, presence of lymphovascular emboli, perinodal extension and grade of the tumor. In multivariate analysis grade of tumor was the only significant factor. CONCLUSIONS: In young women with breast cancer, the factors significantly associated with survival were clinical stage at presentation, the presence of lymphovascular emboli and perinodal extension and grade of tumor. PMID- 26842209 TI - Pedigree studies and evaluation of risk factors of breast cancer in Goa. AB - BACKGROUND: Incidence of breast cancer (BC) is increasing in most of the countries, including the areas which have had previously low rates. AIM: The aim of this prospective study was to analyze the pedigrees of the patients for detecting hereditary factor prevalence and to investigate the possible risk factors associated with BC in a sample population from Goa. MATERIALS AND METHODS: A prospective analysis was performed for 95 BC patients between 2011 and 2012. For assessing the risk factors, a proforma was designed and the necessary data was collected by interview. The process of collecting family history for drawing the pedigree included interviewing the informant. STATISTICAL ANALYSIS USED: Online calculators of statistics were used for standard deviation at www.easycalculation.com and fishers test at www.graphpad.com. RESULTS: High frequency of BC was revealed in the sample population from Goa. This could be attributed to the changes in reproductive patterns, physical inactivity and obesity, or general increase in BC awareness. Factors which did not influence the frequency of BC in the sample population include parity, oral contraceptives, alcohol consumption, occupation, exercise, and nutritional supplement. High incidence of family history of 168/1000 individuals was observed in the present study. CONCLUSIONS: Proper management of BC is possible after assessment of cumulative risk of BC in females by a thorough study of both environmental and genetic factors. Cumulative risk can be greatly reduced by controlling the environmental risk. PMID- 26842210 TI - Young breast cancer: A single center experience. AB - BACKGROUND: Breast cancer in women aged less than 35 years is uncommon and accounts for 1-2% of all breast cancer in the West. There is a paucity of data on young breast cancer from India. The aim of this study was to analyze the clinical, pathological, prognostic factors and outcome in young breast cancer patients. MATERIALS AND METHODS: This analysis was performed in 251 patients aged <35 years or less (defined as breast cancer in the young), who were registered at our institute over an 11 year period between 2001 and 2011. RESULTS: The median age was 31 years (range 18-35). Positive family history (siblings and parents) was elicited in only 10 patients. The TNM stage distribution was: Stage I was 2.5%, stage II - 20.5%, stage III - 55% and stage IV - 22%. The median clinical tumor size was 5.1 cm. Modified radical mastectomy was the most common surgical procedure and this was done in 79% of cases. 40% of tumors were high grade and 60% had pathological node positive disease. Estrogen and Progesterone and human epidermal growth factor receptor 2/neu positivity were 33% and 29% respectively. Triple negative breast cancer constituted 31% of patients. With a median follow up of 30 months, 3 years relapse free survival and overall survival was 51% and 66%. CONCLUSION: Young women constituted 8% of breast cancer cases. Advanced disease at presentation and triple negativity (nearly one third of patients) results poor outcome. PMID- 26842211 TI - Reply to 'comprehensive decongestive therapy in post-mastectomy lymphedema: An Indian perspective'. PMID- 26842212 TI - Effect of aged garlic extract on immune responses to experimental fibrosarcoma tumor in BALB/c mice. AB - BACKGROUND: Aged garlic extract (AGE) has many biological activities including radical scavenging, antioxidative and immunomodulative effects. AIM: In this research work, the antitumor and immunomodulatory effects of AGE against fibrosarcoma implanted tumor were studied. MATERIALS AND METHODS: WEHI-164 fibrosarcoma cells were implanted subcutaneously on day 0 into the right flank of 40 BALB/c mice at age of 8 weeks. Mice were randomly categorized in two separate groups: First received AGE (100 mg/kg, IP), second group as the control group received phosphate buffered saline. Treatments were carried out 3 times/week. Tumor growth was measured and morbidity was recorded. Subpopulations of CD4+/CD8+ T cells were determined using flow cytometry. WEHI-164 cell specific cytotoxicity of splenocytes and in vitro production of interferon gamma (IFN-gamma) and interleukin-4 cytokines were measured. RESULTS: The mice received AGE had significantly longer survival time compared with the control mice. The inhibitory effect on tumor growth was seen in AGE treated mice. The CD4+/CD8+ ratio and in vitro IFN-gamma production of splenocytes were significantly increased in AGE group. WEHI-164 specific cytotoxicity of splenocytes from AGE mice was also significantly increased at 25:1 E: T ratio. CONCLUSION: Administration of AGE resulted in improved immune responses against experimentally implanted fibrosarcoma tumors in BALB/c mice. AGE showed significant effects on inhibition of tumor growth and longevity of survival times. PMID- 26842213 TI - Discordant and aggressive tumor biology of solitary scalp metastasis amidst widespread skeletal metastases in differentiated thyroid carcinoma: Functional radionuclide and MR imaging features and clinical correlates. PMID- 26842214 TI - Ferula gummosa Boiss flower and leaf extracts inhibit angiogenesis in vitro. AB - BACKGROUND: Angiogenesis is a vital process in development as well as in tumor metastasis. Therefore, inhibition of tumor angiogenesis may be an approach for cancer therapy. In this study, we evaluated the effect of Ferula gummosa Boiss flower and leaf extracts on angiogenesis. MATERIALS AND METHODS: Cell growth and cytotoxic effects of different concentrations (0-70 MUg/mL) of F. gummosa Boiss flower and leaf extracts were evaluated on the growth of human umbilical vein endothelial cells (HUVECs) using Neutral Red assay. Then, wound healing, in vitro angiogenesis assay and quantitative VEGF gene expression analysis were conducted with the noncytotoxic concentrations of the ethanol extract. RESULTS: Our results indicated that observed HUVECs viability was higher than 60% for both extracts after 24 hours treatment at concentration of 30 MUg/mL or lower, whereas cytotoxic effects were observed at higher concentrations or after 48 hours treatment. F. gummosa Boiss flower and leaf extracts inhibited migration and angiogenesis capacity in a concentration-dependent manner (10-30 MUg/mL), and down regulated VEGF transcription (20 MUg/mL for flower extract and 30 MUg/mL for leaf extract). CONCLUSIONS: Our findings revealed that F. gummosa Boiss flower and leaf extracts may contain antiangiogenic compounds, which could be used in preparation of new therapeutic agents for inhibition of tumor angiogenesis. To the best of our knowledge, this is the first report of antiangiogenic effects of F. gummosa Boiss flower and leaf extracts and more studies are needed to identify the effective components of the extracts. PMID- 26842215 TI - An interesting case of metastatic thyroid nodules. PMID- 26842217 TI - Saving Newborn Babies - The Benefits of Interventions in Neonatal Care in Norway over More Than 40 Years. AB - The aim of this study was to examine the effect that the introduction of new medical interventions at birth has had on mortality among newborn babies in Norway during the period 1967-2011. During this period, there has been a significant decline in mortality, in particular for low birth weight infants. We identified four interventions that together explained about 50% of the decline in early neonatal and infant mortality: ventilators, antenatal steroids, surfactant and insure. The analyses were performed on a large set of data, encompassing more than 1.6 million deliveries (Medical Birth Registry of Norway). The richness of the data allowed us to perform several robustness tests. Our study indicates that the introduction of new medical interventions has been a very important channel through which the decline in mortality among newborn babies occurred during the second half of the last century. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26842218 TI - Late-onset IgA vasculitis in adult patients exhibits distinct clinical characteristics and outcomes. AB - OBJECTIVES: The aim of this study was to determine whether adult IgA vasculitis patients who developed the disease at an older age differ from early-onset patients in terms of clinical features and outcomes. METHODS: All consecutive adult patients who were diagnosed with IgA vasculitis between January 1997 and December 2014 were reviewed retrospectively. Patients who developed the disease at an older age (>=60 years; late-onset) were compared with those with an earlier onset of disease (<60 years; early-onset). Renal insufficiency was defined as an estimated glomerular filtration rate <60 ml/minute. RESULTS: In total, 100 adult patients were diagnosed with IgA vasculitis (mean age, 45.61 +/- 17.24 years), of whom 31 (31%) had late-onset disease. Compared to early-onset patients, late onset patients were less likely to have a preceding upper respiratory tract infection (0/31, 0.0% vs. 14/69, 20.3%; p=0.004), and more likely to have renal involvement at presentation (27/31, 87.1% vs. 43/69, 62.3%; p=0.017). At the last follow-up visit, late-onset patients were more likely to have chronic renal insufficiency, including end-stage renal disease (18/28, 64.3% vs. 7/62, 11.3%; p=0.000). Multivariate Cox analysis revealed that late-onset was a significant risk factor for renal insufficiency at follow-up (hazard ratio, 16.980, 95% confidence intervals, 4.380-65.830; p=0.000). CONCLUSIONS: Patients with late onset IgA vasculitis in adults exhibit distinct clinical features characterized by greater renal involvement and worse renal outcomes. Thus, watchful follow-up might be needed for adult IgA vasculitis patients, in particular those with late onset disease. PMID- 26842216 TI - Reactive astrocytes undergo M1 microglia/macrohpages-induced necroptosis in spinal cord injury. AB - BACKGROUND: A unique feature of the pathological change after spinal cord injury (SCI) is the progressive enlargement of lesion area, which usually results in cavity formation and is accompanied by reactive astrogliosis and chronic inflammation. Reactive astrocytes line the spinal cavity, walling off the lesion core from the normal spinal tissue, and are thought to play multiple important roles in SCI. The contribution of cell death, particularly the apoptosis of neurons and oligodendrocytes during the process of cavitation has been extensively studied. However, how reactive astrocytes are eliminated following SCI remains largely unclear. RESULTS: By immunohistochemistry, in vivo propidium iodide (PI)-labeling and electron microscopic examination, here we reported that in mice, reactive astrocytes died by receptor-interacting protein 3 and mixed lineage kinase domain-like protein (RIP3/MLKL) mediated necroptosis, rather than apoptosis or autophagy. Inhibiting receptor-interacting protein 1 (RIP1) or depleting RIP3 not only significantly attenuated astrocyte death but also rescued the neurotrophic function of astrocytes. The astrocytic expression of necroptotic markers followed the polarization of M1 microglia/macrophages after SCI. Depleting M1 microglia/macrophages or transplantation of M1 macrophages could significantly reduce or increase the necroptosis of astrocytes. Further, the inflammatory responsive genes Toll-like receptor 4 (TLR4) and myeloid differentiation primary response gene 88 (MyD88) are induced in necroptotic astrocytes. In vitro antagonizing MyD88 in astrocytes could significantly alleviate the M1 microglia/macrophages-induced cell death. Finally, our data showed that in human, necroptotic markers and TLR4/MyD88 were co-expressed in astrocytes of injured, but not normal spinal cord. CONCLUSION: Taken together, these results reveal that after SCI, reactive astrocytes undergo M1 microglia/macrophages-induced necroptosis, partially through TLR/MyD88 signaling, and suggest that inhibiting astrocytic necroptosis may be beneficial for preventing secondary SCI. PMID- 26842219 TI - In vitro and in vivo biological characterization of the anti-proliferative potential of a cyclic trinuclear organotin(iv) complex. AB - Identification of novel molecules that can selectively inhibit the growth of tumor cells, avoid causing side effects to patients and/or intrinsic or acquired resistance, usually associated with common chemotherapeutic agents, is of utmost importance. Organometallic compounds have gained importance in oncologic chemotherapy, such as organotin(iv) complexes. In this study, we assessed the anti-tumor activity of the cyclic trinuclear organotin(iv) complex with an aromatic oximehydroxamic acid group [nBu2Sn(L)]3(H2L = N,2-dihydroxy-5-[N hydroxyethanimidoyl]benzamide) - MG85 - and provided further characterization of its biological targets. We have previously shown the high anti-proliferative activity of this complex against human colorectal and hepatocellular carcinoma cell lines and lower cytotoxicity in neonatal non-tumor fibroblasts. MG85 induces tumor cell apoptosis and down-regulation of proteins related to tubulin dynamics (TCTP and COF1). Further characterization included the: (i) evaluation of interference in the cell cycle progression, including the expression of critical genes; (ii) affinity to DNA and the corresponding mode of binding; (iii) genotoxic potential in cells with deficient DNA repair pathways; and (iv) in vivo tumor reduction efficiency using mouse colorectal carcinoma xenografts. PMID- 26842220 TI - Nocturnal interictal epileptic discharges in adult Lennox-Gastaut syndrome: the effect of sleep stage and time of night. AB - Lennox-Gastaut syndrome (LGS) is characterized by interictal epileptiform discharges (IEDs) occurring during sleep. The aim of this study was to determine whether sleep influences not only the frequency of seizures and IEDs, but also the time-dependent evolution that may support the hypothesis of homeostatic influences on epileptic threshold. Video polysomnography data from our database were reviewed to identify adult LGS patients with at least seven hours of nocturnal recording. Thirteen patients were identified and a second polysomnography was available for nine. The number, duration and index of IEDs, relative to total sleep, sleep stages, and time during the night, were calculated. The majority of IEDs occurred during non-rapid eye movement sleep, mainly in stage 2 and slow-wave sleep. Adjusting for time spent in each sleep stage, we found 45 IEDs/hour in stage 1, 123/hour in stage 2, 106/hour in slow wave sleep, and 26/hour in rapid eye movement sleep. The temporal distribution of IEDs showed a significant rise in the first three hours of sleep, followed by a progressive decrease at the end of the night (F=85.6; p<0.0001). Interictal epileptiform discharges occurrence in adult LGS is facilitated by non-rapid eye movement sleep with an evident effect of stage 2 and slow-wave sleep. The significant IED occurrence in the first part of the night and the subsequent decline suggests a link between epileptic threshold and homeostatic sleep mechanisms. The latter should be considered regarding choice of therapy. PMID- 26842221 TI - Rebuttal from Kenton M. Sanders, Sean M. Ward and Andreas Friebe. PMID- 26842222 TI - Biosynthetic route towards saxitoxin and shunt pathway. AB - Saxitoxin, the most potent voltage-gated sodium channel blocker, is one of the paralytic shellfish toxins (PSTs) produced by cyanobacteria and dinoflagellates. Recently, putative biosynthetic genes of PSTs were reported in these microorganisms. We previously synthesized genetically predicted biosynthetic intermediates, Int-A' and Int-C'2, and also Cyclic-C' which was not predicted based on gene, and identified them all in the toxin-producing cyanobacterium Anabaena circinalis (TA04) and the dinoflagellate Alexandrium tamarense (Axat-2). This study examined the incorporation of (15)N-labeled intermediates into PSTs (C1 and C2) in A. circinalis (TA04). Conversions from Int-A' to Int-C'2, from Int C'2 to Cyclic-C', and from Int-A' and Int-C'2 to C1 and C2 were indicated using high resolution-LC/MS. However, Cyclic-C' was not converted to C1 and C2 and was detected primarily in the extracellular medium. These results suggest that Int-A' and Int-C'2 are genuine precursors of PSTs, but Int-C'2 converts partially to Cyclic-C' which is a shunt product excreted to outside the cells. This paper provides the first direct demonstration of the biosynthetic route towards saxitoxin and a shunt pathway. PMID- 26842224 TI - Cofilin-induced cooperative conformational changes of actin subunits revealed using cofilin-actin fusion protein. AB - To investigate cooperative conformational changes of actin filaments induced by cofilin binding, we engineered a fusion protein made of Dictyostelium cofilin and actin. The filaments of the fusion protein were functionally similar to actin filaments bound with cofilin in that they did not bind rhodamine-phalloidin, had quenched fluorescence of pyrene attached to Cys374 and showed enhanced susceptibility of the DNase loop to cleavage by subtilisin. Quantitative analyses of copolymers made of different ratios of the fusion protein and control actin further demonstrated that the fusion protein affects the structure of multiple neighboring actin subunits in copolymers. Based on these and other recent related studies, we propose a mechanism by which conformational changes induced by cofilin binding is propagated unidirectionally to the pointed ends of the filaments, and cofilin clusters grow unidirectionally to the pointed ends following this path. Interestingly, the fusion protein was unable to copolymerize with control actin at pH 6.5 and low ionic strength, suggesting that the structural difference between the actin moiety in the fusion protein and control actin is pH-sensitive. PMID- 26842225 TI - Standardisation of minimal erythematous dose reading and assessment: a new system. AB - BACKGROUND/PURPOSE: Sunscreen efficacy is usually expressed by the sun protection factor (SPF) which is calculated by establishing the minimum erythematous dose (MED), i.e. the smallest amount of energy required to trigger erythema. Efforts have been made to harmonise SPF testing but in vivo SPF methodology could still be improved to reduce its variability. This article proposes a means of standardising MED evaluations through the development and validation of an MED assessment system based on image analysis. METHODS: The MED assessment system comprises a camera combined with a black tube for acquiring pictures of the skin surface. Specific software was then developed to analyse these pictures to determine the MED based on the shape, size and colour of the exposed zones. The MED assessment system was validated through two studies. The first study was designed to assess the correlation between three expert graders who visually determined the MEDs in five subjects on whom three different suncare products (SPF 6, SPF 30 and SPF 50+) were tested. The second study correlated results obtained from one expert grader with those from a grader assisted by the new MED assessment system. RESULTS: Results of the first study showed substantial variation between graders, with kappa agreement as low as 0.59 (percentage error 19.7%). Results of the study assessing correlation between the expert grader and the grader facilitated by the new MED assessment device showed better correlation, with a kappa value of 0.75 and percentage error of 9.61%. CONCLUSION: A high degree of inter-grader variability was seen when MED was assessed by expert graders. The new MED assessment system provides background colour correction and standardisation to enable accurate MED determination. A high level of correlation was seen between the expert grader and the new MED assessment system, thus demonstrating its potential utility in more accurate and homogenous MED evaluations. Future multicentre studies are required to improve and validate the standardised MED determination for suncare products and to further evaluate the role of this new MED assessment system. However, these preliminary results are encouraging and may set the scene for this new MED assessment system to become the standard of the future. PMID- 26842226 TI - Attrition and weight loss outcomes for patients with complex obesity, anxiety and depression attending a weight management programme with targeted psychological treatment. AB - The objective of the study is to investigate the effect of baseline anxiety and depression, using different definitions for caseness, on attrition and weight outcomes following a multidisciplinary weight management programme. The study design is a prospective observational study. The Hospital Anxiety and Depression Scale (HADS) was used to measure anxiety and depression with 'caseness' scoring >=11 and severity >=14. The participants were all patients who began a weight management programme between 1 October 2008 and 30 September 2009 (n = 1838). The setting was the Glasgow and Clyde Weight Management Service (GCWMS), a specialist multidisciplinary service, which aims to achieve a minimum of >=5 kg weight loss. The results were as follows: patients with HADS score >=14 were referred to the integrated psychology service for psychological assessment or intervention. Patients with caseness (HADS >=11) for anxiety (33%) and depression (27%) were significantly younger, heavier, more socio-economically deprived and a higher proportion was female. There was a significant positive correlation between HADS anxiety and depression scores and increasing body mass index (r(2) = 0.094, P < 0.001 and r(2) = 0.175, P < 0.001, respectively). Attendance and completion was lower throughout follow-up amongst patients with anxiety or depression. More patients with HADS score >=11 achieved >=5 kg or >=5% weight loss and by 12 months those with anxiety had a significantly higher mean weight loss (P = 0.032). Participants who scored for severe anxiety (HADS >=14) achieved similar weight loss to those without, whilst participants who scored for severe depression achieved significantly greater weight loss than non-cases at 3, 6 and 12 months of follow-up (P < 0.01). Despite a less favourable case-mix of risk factors for poor weight loss, patients who scored caseness for severe anxiety or depression and were offered additional psychological input achieved similar or better weight loss outcomes. PMID- 26842227 TI - Epidural analgesia does not increase the rate of inpatient falls after major upper abdominal and thoracic surgery: a retrospective case-control study. AB - PURPOSE: Postoperative epidural analgesia for major upper abdominal and thoracic surgery can provide significant benefits, including superior analgesia and reduced pulmonary dysfunction. Nevertheless, epidural analgesia may also be associated with decreased muscle strength, sympathetic tone, and proprioception that could possibly contribute to falls. The purpose of this retrospective case control study was to search a large national database in order to investigate the possible relationship between postoperative epidural analgesia and the rate of inpatient falls. METHODS: Data from the nationwide inpatient sample for 2007-2011 were queried for adult patients who underwent elective major upper abdominal and thoracic surgery. Multiple International Classification of Diseases, Ninth Revision, Clinical Modification codes for inpatient falls and accidents were combined into one binary variable. Univariate analyses were used for initial statistical analysis. Logistic regression analyses and McNemar's tests were subsequently used to investigate the association of epidural analgesia with inpatient falls in a 1:1 case-control propensity-matched sample after adjustment of patients' demographics, comorbidities, and hospital characteristics. RESULTS: Forty-two thousand six hundred fifty-eight thoracic and 54,974 upper abdominal surgical procedures were identified. The overall incidence of inpatient falls in the thoracic surgery group was 6.54% with an increasing trend over the study period from 4.95% in 2007 to 8.11% in 2011 (P < 0.001). Similarly, the overall incidence of inpatient falls in the upper abdominal surgery group was 5.30% with an increasing trend from 4.55% in 2007 to 6.07% in 2011 (P < 0.001). Postoperative epidural analgesia was not associated with an increased risk for postoperative inpatient falls in the thoracic surgery group (relative risk [RR], 1.18; 95% confidence interval [CI], 0.95 to 1.47; P = 0.144) and in the upper abdominal surgery group (RR, 0.84; 95% CI 0.64 to 1.09; P = 0.220). Inpatient falls compared with non-falls were associated with a longer median (interquartile range) length of hospital stay in both the thoracic surgery group (11 [7-17] days vs 9 [6-16] days, respectively; P < 0.001) and the upper abdominal surgery group (12 [7-20] days vs 10 [6-17] days, respectively; P < 0.001). CONCLUSION: Our study suggests that postoperative epidural analgesia for patients undergoing major upper abdominal and thoracic surgery is not associated with an increased risk of inpatient falls. PMID- 26842228 TI - Do the Elderly Get the Message? A Comparative Study of Stories Produced Verbally and as a Text Message. AB - When young adults re-tell a story, they naturally produce more concise but sufficiently informative narratives. The repeated narratives of elderly adults, on the other hand, tend towards prolixity. In the present study, participants were explicitly instructed to re-tell a story in a more succinct (but informative format) to investigate whether they were able to produce informative narratives in a compressed format. 30 younger adults ([Formula: see text]) and 30 older adults ([Formula: see text]) constructed a verbal narrative from a series of cartoon frames depicting a story about a cowboy and his horse. Participants then re-told this narrative as a text message. The second narrative produced by the older adult sample did on average contain fewer words, but at the expense of informative content and discourse cohesion. The tendency of older adults to produce longer narratives with re-telling is not merely reflective of a strategic choice but rather reflects a genuine macrolinguistic deficit. PMID- 26842229 TI - Government and national bodies take charge of decision making as NHS crisis grows. PMID- 26842230 TI - A novel approach in psoriasis: first usage of known protein oxidation markers to prove oxidative stress. AB - Oxidative stress may play a pivotal role in the pathogenesis of psoriasis, an inflammatory/hyperproliferative skin disease characterized by the cutaneous accumulation of neutrophils releasing reactive oxygen species, as revealed in a number of studies. This study was performed to demonstrate the presence of oxidative stress in psoriasis, as measured by protein oxidation markers. Twenty nine psoriasis patients were selected based on disease severity assessment using body surface area as well as the psoriasis area severity index (PASI), and were grouped as mild (PASI <= 10) and moderate-to-severe (PASI > 10). The measured parameters in psoriatic patients and fourteen healthy volunteers were as follows: erythrocyte sedimentation rate (ESR), high sensitive C-reactive protein (CRP), myeloperoxidase (MPO) activity, neopterin, total lipid hydroperoxides (LHP), pyrrolized protein (PP), protein carbonyl compounds (PCC), advanced oxidation protein products (AOPP), thiol levels, along with complete blood count. Except lower thiols, all parameters were found to be higher in total patients as well as in subgroups, compared to controls. There was no significant difference among the subgroups. In conclusion, protein oxidation in psoriatics, not only in moderate to-severe, but also in mild patients, may be explained by the findings of inflammation, phagocytic cell oxidation, and MPO-hypochlorous acid-oxidation reactions; as reflected by increased total/differential leucocytes counts, CRP, ESR as well as MPO, neopterin, AOPP, PCC, PP, LHP, and decreased thiol levels. Demonstrating the AOPP and PP formation for the first time, oxidants from active neutrophils/monocytes may play an important role in the pathogenesis of psoriasis, leading to oxidative stress, especially by protein oxidation. PMID- 26842231 TI - Exploration of scalp surface lipids reveals squalene peroxide as a potential actor in dandruff condition. AB - Dandruff is a common but complex disorder with three major contributing factors: (1) individual predisposition, (2) scalp sebum and (3) Malassezia yeast colonization. To obtain further insights into the role of sebum in dandruff biogenesis, we analyzed scalp lipid species in a cohort of ten dandruff-free (control) and ten dandruff-afflicted volunteers by gas chromatography coupled to mass spectrometry. Lipid peroxidation levels and biochemical markers of oxidative stress were also assessed. Squalene, a major sebum component, was significantly more peroxidized in dandruff-affected scalps, resulting in significantly higher ratios of squalene monohydroperoxide (SQOOH)/squalene. This was observed when comparing dandruff-affected zones of dandruff subjects to both their non-affected zones and control subjects. In addition, other biomarkers such as malondialdehyde indicated that oxidative stress levels were raised on dandruff scalps. Surprisingly, differences regarding either free or bound fatty acids were fairly rare and minor. Certain novel findings, especially squalene peroxidation levels, were then confirmed in a validation cohort of 24 dandruff-affected subjects, by comparing dandruff-affected and non-dandruff zones from the same individuals. As SQOOH can induce both keratinocyte inflammatory responses and hyperproliferation in vitro, we hypothesized that increased SQOOH could be considered as a new etiological dandruff factor via its ability to impair scalp barrier function. Our results also indicated that Malassezia could be a major source of squalene peroxidation on the scalp. PMID- 26842232 TI - Correlation between cell cycle proteins and hMSH2 in actinic cheilitis and lip cancer. AB - This study aims to evaluate and verify the relationship between the immunoexpression of hMSH2, p53 and p21 in actinic cheilitis (AC) and lower lip squamous cell carcinoma (SCC) cases. Forty AC and 40 SCC cases were submitted to immunoperoxidase method and quantitatively analyzed. Expression was compared by Mann-Whitney test, Student t test or one-way ANOVA. To correlate the variables, Pearson's correlation coefficient was calculated. The expression of p53 and p21 showed no significant differences between histopathological grades of AC or lower lip SCC (p > 0.05). Immunoexpression of p53 was higher in SCC than in AC (p < 0.001), while p21 expression was more observed in AC when compared to SCC group (p = 0.006). The AC group revealed an inverse correlation between p53 and hMSH2 expression (r = -0.30, p = 0.006). Alterations in p53 and p21 expression suggest that these proteins are involved in lower lip carcinogenesis. Moreover, p53 and hMSH2 seem to be interrelated in early events of this process. PMID- 26842233 TI - Erratum to: What Middle Phalanx Base Fracture Characteristics are Most Reliable and Useful for Surgical Decision-making? PMID- 26842234 TI - Of Mice and Melanoma: PDX System for Modeling Personalized Medicine. AB - Targeted therapies have advanced the treatment options for cutaneous melanoma, but many patients will progress on drug. Patient-derived xenografts (PDX) can be used to recapitulate therapy-resistant tumors. Furthermore, PDX modeling can be utilized in combination with targeted sequencing and phosphoproteomic platforms, providing preclinical basis for second-line targeted inhibitor strategies. See related article by Krepler et al., p. 1592. PMID- 26842235 TI - A Novel Epigenetic Signature for Early Diagnosis in Lung Cancer. AB - PURPOSE: Lung cancer remains as the leading cause of cancer-related death worldwide, mainly due to late diagnosis. Cytology is the gold-standard method for lung cancer diagnosis in minimally invasive respiratory samples, despite its low sensitivity. We aimed to identify epigenetic biomarkers with clinical utility for cancer diagnosis in minimally/noninvasive specimens to improve accuracy of current technologies. EXPERIMENTAL DESIGN: The identification of novel epigenetic biomarkers in stage I lung tumors was accomplished using an integrative genome wide restrictive analysis of two different large public databases. DNA methylation levels for the selected biomarkers were validated by pyrosequencing in paraffin-embedded tissues and minimally invasive and noninvasive respiratory samples in independent cohorts. RESULTS: We identified nine cancer-specific hypermethylated genes in early-stage lung primary tumors. Four of these genes presented consistent CpG island hypermethylation compared with nonmalignant lung and were associated with transcriptional silencing. A diagnostic signature was built using multivariate logistic regression model based on the combination of four genes: BCAT1, CDO1, TRIM58, and ZNF177 Clinical diagnostic value was also validated in multiple independent cohorts and yielded a remarkable diagnostic accuracy in all cohorts tested. Calibrated and cross-validated epigenetic model predicts with high accuracy the probability to detect cancer in minimally and noninvasive samples. We demonstrated that this epigenetic signature achieved higher diagnostic efficacy in bronchial fluids as compared with conventional cytology for lung cancer diagnosis. CONCLUSIONS: Minimally invasive epigenetic biomarkers have emerged as promising tools for cancer diagnosis. The herein obtained epigenetic model in combination with current diagnostic protocols may improve early diagnosis and outcome of lung cancer patients. Clin Cancer Res; 22(13); 3361-71. (c)2016 AACR. PMID- 26842236 TI - Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of the Poly(ADP ribose) Polymerase (PARP) Inhibitor Veliparib (ABT-888) in Combination with Irinotecan in Patients with Advanced Solid Tumors. AB - PURPOSE: PARP is essential for recognition and repair of DNA damage. In preclinical models, PARP inhibitors modulate topoisomerase I inhibitor-mediated DNA damage. This phase I study determined the MTD, dose-limiting toxicities (DLT), pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib, an orally bioavailable PARP1/2 inhibitor, in combination with irinotecan. EXPERIMENTAL DESIGN: Patients with advanced solid tumors were treated with 100 mg/m(2) irinotecan on days 1 and 8 of a 21-day cycle. Twice-daily oral dosing of veliparib (10-50 mg) occurred on days 3 to 14 (cycle 1) and days -1 to 14 (subsequent cycles) followed by a 6-day rest. PK studies were conducted with both agents alone and in combination. Paired tumor biopsies were obtained after irinotecan alone and veliparib/irinotecan to evaluate PARP1/2 inhibition and explore DNA damage signals (nuclear gamma-H2AX and pNBS1). RESULTS: Thirty-five patients were treated. DLTs included fatigue, diarrhea, febrile neutropenia, and neutropenia. The MTD was 100 mg/m(2) irinotecan (days 1 and 8) combined with veliparib 40 mg twice daily (days -1-14) on a 21-day cycle. Of 31 response evaluable patients, there were six (19%) partial responses. Veliparib exhibited linear PK, and there were no apparent PK interactions between veliparib and irinotecan. At all dose levels, veliparib reduced tumor poly(ADP-ribose) (PAR) content in the presence of irinotecan. Several samples showed increases in gamma H2AX and pNBS1 after veliparib/irinotecan compared with irinotecan alone. CONCLUSIONS: Veliparib can be safely combined with irinotecan at doses that inhibit PARP catalytic activity. Preliminary antitumor activity justifies further evaluation of the combination. Clin Cancer Res; 22(13); 3227-37. (c)2016 AACR. PMID- 26842237 TI - Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer. AB - PURPOSE: Recent data suggest that intrinsic subtype and immune cell infiltration may predict response to trastuzumab-based therapy. We studied the interaction between these factors, changes in immune signatures following brief exposure to trastuzumab, and achievement of pathologic complete response (pCR) to subsequent preoperative trastuzumab and chemotherapy in HER2-positive breast cancer. EXPERIMENTAL DESIGN: In patients enrolled on two multicenter trials (03-311 and 211B), tumor core biopsies were obtained at baseline and after brief exposure to single-agent trastuzumab or nab-paclitaxel. Gene expression profiles were assessed to assign PAM50 subtypes, measure immune cell activation, and were correlated with response. RESULTS: The pCR rate was significantly higher in HER2 enriched tumors in the Discovery, 03-311 (36%, P = 0.043) dataset, as compared with other subtypes, which validated in 211B (50%, P = 0.048). Significant increases in a signature of immune cell admixture (Immune Index) were observed only following brief exposure to trastuzumab in HER2-enriched tumors (Discovery/03-311, P = 0.05; Validation/211B, P = 0.02). Increased Immune Index was predictive of response after brief exposure (03-311, P = 0.03; 211B, P = 0.04), but not at baseline, in addition to increased expression of a CD4(+) follicular helper T-cell signature (03-311, P = 0.05; 211B, P = 0.04). Brief exposure to trastuzumab significantly increased gene expression of the T-cell marker PD-1 in HER2-enriched tumors (Discovery/03-311, P = 0.045) and PD-1 positivity by IHC (Validation/211B, P = 0.035). CONCLUSIONS: Correlations between pCR rates, increases in Immune Index and markers of T-cell activity following brief exposure to trastuzumab in HER2-enriched tumors provide novel insights into the interaction between tumor biology, antitumor immunity, and response to treatment, and suggest potential clinically useful biomarkers in HER2(+) breast cancers. Clin Cancer Res; 22(13); 3249-59. (c)2016 AACR. PMID- 26842239 TI - Application of multivariate statistical analysis and hydrochemical and isotopic investigations for evaluation of groundwater quality and its suitability for drinking and agriculture purposes: case of Oum Ali-Thelepte aquifer, central Tunisia. AB - Groundwater plays a dominant role in arid regions; it is among the most available water resources in Tunisia. Located in northwestern Tunisia, Oum Ali-Thelepte is a deep Miocene sedimentary aquifer, where groundwater is the most important source of water supply. The aim of the study is to investigate the hydrochemical processes leading to mineralization and to assess water quality with respect to agriculture and drinking for a better management of groundwater resources. To achieve such objectives, water analysis was carried out on 16 groundwater samples collected during January-February 2014. Stable isotopes and 26 hydrochemical parameters were examined. The interpretation of these analytical data showed that the concentrations of major and trace elements were within the permissible level for human use. The distribution of mineral processes in this aquifer was identified using conventional classification techniques, suggesting that the water facies gradually changes from Ca-HCO3 to Mg-SO4 type and are controlled by water-rock interaction. These results were endorsed using multivariate statistical methods such as principal component analysis and cluster analysis. The sustainability of groundwater for drinking and irrigation was assessed based on the water quality index (WQI) and on Wilcox and Richards's diagrams. This aquifer has been classified as "excellent water" serving good irrigation in the area. As for the stable isotope, the measurements showed that groundwater samples lay between global meteoric water line (GMWL) and LMWL; hence, this arrangement signifies that the recharge of the Oum Ali-Thelepte aquifer is ensured by rainwater infiltration through mountains in the border of the aquifer without evaporation effects. PMID- 26842238 TI - The Role of Neoadjuvant Trials in Drug Development for Solid Tumors. AB - The relatively low success rate of phase II oncology trials in predicting success of novel drugs in phase III trials and in gaining regulatory approval may be due to reliance on the endpoint of response rate defined by the RECIST. The neoadjuvant treatment paradigm allows the antitumor activity of a novel therapy to be determined on a pathologic basis at the time of surgery instead of by RECIST, which was not developed to guide clinical decision making or correlate with long-term outcomes. Indeed, the FDA endorsed pathologic complete response (pCR) as a surrogate for overall survival (OS) in early-stage breast cancer and granted accelerated approval to pertuzumab based on this endpoint. We propose that pCR is a biologically rational method of determining treatment effect that may be more likely to predict OS. We discuss some advantages of the neoadjuvant trial design, review the use of neoadjuvant therapy as standards of care, and consider the neoadjuvant platform as a method for drug development. Clin Cancer Res; 22(10); 2323-8. (c)2016 AACR. PMID- 26842240 TI - Risk assessment of heavy metals via consumption of vegetables collected from different supermarkets in La Rochelle, France. AB - In this study, a food survey was carried out with two purposes: (1) to investigate the levels of nickel (Ni), zinc (Zn), and copper (Cu) in various vegetables randomly collected in supermarkets of La Rochelle and (2) to assess the potential health risk for consumers by estimating the daily intake (EDI) and the target hazard quotient (THQ) for each heavy metal. The concentrations of Ni, Cu, and Zn in selected foodstuffs were detected within the following ranges: (3.2 9.6), (25.2-104.7), and (10.8-75.6) mg/kg (DW), respectively. Results showed that metals are more likely to accumulate in fruit vegetables (8.8, 63.8 and 47.8 mg/kg DW for Ni, Cu, and Zn, respectively), followed by leafy vegetables (6.5, 60.9 and 42.6 mg/kg DW for Ni, Cu, and Zn, respectively) and finally root vegetables (5.4, 40.0 and 27.3 mg/kg DW for Ni, Cu, and Zn, respectively). The levels of the metals match with those reported for similar vegetables from some other parts of the world. For all foodstuffs, EDI and THQ were below the threshold values for Cu (EDI 11.30; THQ 0.283) and Zn (EDI 6.86; THQ 0.023), while they exceeded the thresholds for Ni (EDI 20.71; THQ 1.035), indicating an obvious health risk over a life time of exposure. PMID- 26842241 TI - Water quality assessment of river Beas, India, using multivariate and remote sensing techniques. AB - River Beas originates in the Himalayas and merges into river Sutlej at Harike, a Ramsar wetland. This river is a habitat of the endangered freshwater dolphin, Platanista gangetica minor R. Twenty-five water quality parameters, including eight heavy metals, were studied at four sampling sites over a stretch of 63 km between Beas and Harike towns for pre-monsoon, post-monsoon and winter seasons. Principal component analysis of the data proved to be an effective tool for data reduction as the first three principal components of all the water quality parameters explained 100% variance. Factor analysis delineated three factors underlying the water quality. Factor 1 comprised pollution-related parameters like BOD, COD, DO, PO4(-3) and hardness. Factor 2 was a natural water quality determinant and explained maximum variance in turbidity, alkalinity and TDS. Factor 3 comprised NO3(-1), a fertilizer-related parameter. Reflectance values from bands 2 (green), 3 (red) and 4 (near infra-red) of Landsat (TM) digital data were regressed on PO4(-3), turbidity and TDS using multiple linear regression analysis. PO4(-3) contributed positively to the spectral radiance, whereas TDS contributed negatively. Beta regression analysis revealed that PO4(-3) had a positive relation with BOD, whereas turbidity and TDS were negatively regressed with BOD. Artificial neural network models were fitted to the data. Correlations between the target values from ANN for turbidity, BOD and bands 2 (green), 3 (red) and 4 (near infra-red) were highly significant. PMID- 26842242 TI - Individual speckle diffraction based 1D and 2D Random Grating Fabrication for detector and solar energy harvesting applications. AB - Laser speckles and speckle patterns, which are formed by the random interference of scattered waves from optically rough surfaces, have found tremendous applications in a wide range of metrological and biomedical fields. Here, we demonstrate a novel edge diffraction phenomenon of individual speckle for the fabrication of 1D and 2D micron and sub-micron size random gratings. These random gratings exhibit broadband response with interesting diffusive diffraction patterns. As an immediate application for solar energy harvesting, significant reduction in transmission and enhanced absorption in thin "Si-random grating-Si" sandwich structure is demonstrated. This work has multifaceted significance where we exploited the individual speckle diffraction properties for the first time. Besides the solar harvesting applications, random gratings are suitable structures for fabrication of theoretically proposed random quantum well IR detectors and hence expected that this work will augur well for such studies in the near future. PMID- 26842243 TI - Alcoholic Hepatitis: Risk Factors, Pathogenesis, and Approach to Treatment. AB - BACKGROUND: Alcoholic hepatitis (AH) is an inflammatory disorder of the liver characterized clinically by jaundice, hepatomegaly, and abdominal pain, and histologically by macrovesicular steatosis and necroinflammation. METHODS: This clinical review will cover what is known about the pathogenesis, clinical presentation, current treatments, and novel therapies for AH. RESULTS: The pathogenesis and treatment of AH remain areas of active research. Although abstinence is the cornerstone of therapy for all stages of alcoholic liver disease, corticosteroids have shown modest short-term benefits in treatment of severe AH. CONCLUSIONS: Improved understanding of the pathogenesis of AH has expanded the range of potential treatments for this devastating disease. Several novel therapies are also currently in various stages of testing through clinical trials. PMID- 26842244 TI - A Call for Research on High-Intensity Alcohol Use. PMID- 26842245 TI - Role of Growth Arrest and DNA Damage-Inducible, Beta in Alcohol-Drinking Behaviors. AB - BACKGROUND: The contribution of epigenetic factors, such as histone acetylation and DNA methylation, to the regulation of alcohol-drinking behavior has been increasingly recognized over the last several years. GADD45b is a protein demonstrated to be involved in DNA demethylation at neurotrophic factor gene promoters, including at brain-derived neurotrophic factor (Bdnf) which has been highly implicated in alcohol-drinking behavior. METHODS: DNA methyltransferase-1 (Dnmt1), 3a, and 3b, and Gadd45a, b, and g mRNA were measured in the nucleus accumbens (NAc) and ventral tegmental areas of high ethanol (EtOH) consuming C57BL/6J (C57) and low alcohol consuming DBA/2J (DBA) mice using quantitative reverse transcriptase polymerase chain reaction (PCR). In the NAc, GADD45b protein was measured via immunohistochemistry and Bdnf9a mRNA using in situ PCR. Bdnf9a promoter histone H3 acetylated at lysines 9 and 14 (H3K9,K14ac) was measured using chromatin immunoprecipitation, and 5-methylcytosine (5MC) and 5 hydroxymethylcytosine (5HMC) using methylated DNA immunoprecipitation. Alcohol drinking behavior was evaluated in Gadd45b haplodeficient (+/-) and null mice (-/ ) utilizing drinking-in-the-dark (DID) and 2-bottle free-choice paradigms. RESULTS: C57 mice had lower levels of Gadd45b and g mRNA and GADD45b protein in the NAc relative to the DBA strain. C57 mice had lower NAc shell Bdnf9a mRNA levels, Bdnf9a promoter H3K9,K14ac, and higher Bdnf9a promoter 5HMC and 5MC. Acute EtOH increased GADD45b protein, Bdnf9a mRNA, and histone acetylation and decreased 5HMC in C57 mice. Gadd45b +/- mice displayed higher drinking behavior relative to wild-type littermates in both DID and 2-bottle free-choice paradigms. CONCLUSIONS: These data indicate the importance of the DNA demethylation pathway and its interactions with histone posttranslational modifications in alcohol drinking behavior. Further, we suggest that lower DNA demethylation protein GADD45b levels may affect Bdnf expression possibly leading to altered alcohol drinking behavior. PMID- 26842247 TI - Association Study of Gene Polymorphisms in GABA, Serotonin, Dopamine, and Alcohol Metabolism Pathways with Alcohol Dependence in Taiwanese Han Men. AB - BACKGROUND: The roles of GABA, serotonin, dopamine, and alcohol metabolism pathways in alcohol dependence (AD) are evident from animal models and human studies. Aims of this study were to investigate associations between genes in the 4 pathways and AD. METHODS: Male subjects from 2 independent samples of Taiwanese Han descent, a family sample of 179 trios and a case-control sample of 262 AD cases and 273 normal controls, were included in this study. The Schedules for Clinical Assessment in Neuropsychiatry was used for phenotype assessment of AD. We genotyped 282 single nucleotide polymorphisms (SNPs) located in 61 candidate genes involving alcohol metabolism, serotonin, and GABA systems among the family sample and replicated the top hits in the case-control sample. RESULTS: Fifteen SNPs located in 10 genes showed signals of associations (FBAT test p < 0.05) with AD in the family sample. Three SNPs, rs1229984 in ADH1B, rs671 in ALDH2, and rs2000292 in HTR1B, were significantly replicated in the case-control sample (p = 5.87 * 10(-14) , 5.12 * 10(-14) , and 0.0051, respectively). In the combined meta analysis, these 3 SNPs and 1 additional SNP, rs698 in ADH1C, showed significant association after correcting for multiple comparisons, and rs1229984 and rs671 showed the strongest association (p < 10(-16) ). Logistic regression conditioning on rs1229984 and rs671 in the case-control sample showed that rs2000292 in HTR1B remained nominally significant. CONCLUSIONS: Genes in alcohol metabolism pathway, especially ADH1B and ALDH2, conferred the major genetic risk for AD in Taiwanese Han population. Some genes in GABA and serotonin pathways showed nominal association with AD. PMID- 26842248 TI - Chronic Alcohol Consumption in Rats Leads to Desynchrony in Diurnal Rhythms and Molecular Clocks. AB - BACKGROUND: Circadian rhythms are essential for adapting to the environment. Chronic alcohol consumption often leads to sleep and circadian disruptions, which may impair the life quality of individuals with alcohol use disorders and contribute to the morbidity associated with alcoholism. METHODS: We used a pair feeding liquid diet alcohol exposure protocol (6 weeks duration) in PER1::LUC transgenic rats to examine the effects of chronic alcohol exposure on: (i) diurnal rhythms of core body temperature and locomotor activity, (ii) plasma corticosterone (CORT) concentrations, and (iii) rhythms of ex vivo Period1 (Per1) expression in the suprachiasmatic nucleus (SCN), pituitary, and adrenal glands. We followed multiple circadian outputs not only to examine individual components, but also to assess the relative phase relationships among rhythms. RESULTS: We found that chronic alcohol consumption: (i) reduced 24-hour body temperature and locomotor activity counts in the dark period, (ii) advanced the acrophase of diurnal rhythms of body temperature and locomotor activity, (iii) abolished the phase difference between temperature and activity rhythms, (iv) blunted and advanced the diurnal CORT rhythm, and (v) advanced Per1 expression in the adrenal and pituitary glands but not in the SCN. We found that chronic alcohol altered the phase relationships among diurnal rhythms and between the central (SCN) and peripheral (adrenal and pituitary) molecular clocks. CONCLUSIONS: Our findings suggest that desynchrony among internal rhythms is an important and overlooked aspect of alcohol-induced circadian disruptions. The misalignment of phases among rhythms may compromise normal physiological functions and put individuals with chronic alcohol use at greater risk for developing other physical and mental health issues. How this desynchrony occurs and the extent to which it participates in alcohol-related pathologies requires further investigation. PMID- 26842246 TI - Alcohol Decreases Organic Dust-Stimulated Airway Epithelial TNF-Alpha Through a Nitric Oxide and Protein Kinase-Mediated Inhibition of TACE. AB - BACKGROUND: Farm workers in rural areas consume more alcohol than those who reside in urban areas. Occupational exposures such as agricultural work can pose hazards on the respiratory system. It is established that hog barn dust induces inflammation in the airway, including the release of cytokines such as tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and IL-8. We have shown that alcohol alters airway epithelial innate defense through changes in both nitric oxide (NO) and cAMP-dependent protein kinase A (PKA). Simultaneous exposure to hog barn dust and alcohol decreases inflammatory mediators, TNF alpha, IL-6, and IL-8, in mice. Previously, mice exposed to both alcohol and hog barn dust showed a depleted amount of lymphocytes compared to mice exposed only to hog barn dust. Weakening of the innate immune response could lead to enhanced susceptibility to disease. In addition, mice that were co-exposed to hog barn dust and alcohol also experienced increased mortality. METHODS: Because we recently demonstrated that PKA activation inhibits the TNF-alpha sheddase, TNF alpha-converting enzyme (TACE), we hypothesized that an alcohol-mediated PKA pathway blocks TACE activity and prevents the normative inflammatory response to hog barn dust exposure. To delineate these effects, we used PKA pathway inhibitors (adenylyl cyclase [AC], cAMP, and PKA) to modulate the effects of alcohol on dust-stimulated TNF-alpha release in the bronchial epithelial cell line, BEAS-2B. Alcohol pretreatment blocked TACE activity and TNF-alpha release in hog barn dust-treated cells. RESULTS: Alcohol continued to block hog barn dust mediated TNF-alpha release in the presence of the particulate AC inhibitor, SQ22,536. The soluble adenylyl cyclase inhibitor, KH7, however, significantly increased the inflammatory response to hog barn dust. phosphodiesterase 4 inhibitors significantly elevated cAMP and enhanced alcohol-mediated inhibition of dust-stimulated TNF-alpha release. In addition, the NO synthase inhibitor, l NMMA, also reversed the alcohol-blocking effect on dust-stimulated TNF-alpha. CONCLUSIONS: These data suggest that alcohol requires a soluble cyclase-generated cAMP-PKA pathway that is dependent upon the action of NO to inhibit TACE and TNF alpha release. These findings support our observations that alcohol functions through a dual NO and PKA pathway in bronchial epithelial cells. PMID- 26842250 TI - Neonatal Ethanol Exposure Impairs Trace Fear Conditioning and Alters NMDA Receptor Subunit Expression in Adult Male and Female Rats. AB - BACKGROUND: Ethanol (EtOH) exposure in neonate rats during a period comparable to the human third trimester, postnatal days (PD) 4 to 9, leads to persistent deficits in forebrain-dependent cognitive function--modeling the dysfunction seen in individuals diagnosed with fetal alcohol spectrum disorders. EtOH-exposed adult rats are impaired in auditory trace fear conditioning (TFC), a form of Pavlovian conditioning in which a neutral conditioned stimulus (CS; tone) is followed by an aversive unconditioned stimulus (US; footshock), with both stimuli separated in time by a stimulus-free "trace" interval (TI). TFC acquisition depends on N-methyl-d-aspartate NMDA receptor (NMDAR) activation in the dorsal hippocampus (DH), ventral hippocampus (VH), and medial prefrontal cortex (mPFC). METHODS: Male and female rat pups were sham-intubated (SI) or intragastrically intubated with EtOH (5E; 5 g/kg/d) over PD 4 to 9 and, as adults, submitted to TFC with a 15-second tone CS and 30-second TI. Whole-cell tissue lysates from the DH, VH, and mPFC of TFC rats and DH synaptic/extrasynaptic membrane fractions from experimentally naive animals were analyzed via Western blot for NMDAR subunit (GluN1, GluN2A, GluN2B) expression. RESULTS: Freezing behavior during CS alone test trials was significantly reduced in both male and female 5E rats, relative to same-sex controls. Western blot results based on DH tissue samples revealed a greater proportion of GluN2A to GluN2B subunits in 5E rats, relative to SI rats, and significantly reduced synaptic GluN2B and PSD-95 expression. CONCLUSIONS: EtOH-induced changes in DH NMDAR subunit expression-particularly synaptic GluN2B, which is critical for TFC-are proposed to weaken long-term memory consolidation and, during behavioral testing, diminish CS-evoked freezing behavior. PMID- 26842249 TI - Inhibitors of Calcium-Activated Anion Channels Modulate Hypnotic Ethanol Responses in Adult Sprague Dawley Rats. AB - BACKGROUND: Ethanol is widely known for its depressant effects; however, the underlying neurobiological mechanisms are not clear. Calcium-activated anion channels (CAACs) contribute to extracellular chloride levels and thus may be involved in regulating inhibitory mechanisms within the central nervous system. Therefore, we hypothesized that CAACs influence ethanol behavioral sensitivity by altering CAAC expression. METHODS: We assessed the role of CAACs in ethanol induced loss of righting reflex (LORR) and locomotor activity using intracerebroventricular infusions of several nonselective CAAC blockers. CAAC expression was determined after ethanol exposure. RESULTS: Ethanol-induced LORR (4.0 g/kg, intraperitoneally [i.p.]) was significantly attenuated by all 4 CAAC blockers. Blocking CAACs did not impact ethanol's low-dose (1.5 g/kg, i.p.) locomotor-impairing effects. Biochemical analysis of CAAC protein expression revealed that cortical Bestrophin1 (Best1) and Tweety1 levels were reduced as early as 30 minutes following a single ethanol injection (3.5 g/kg, intraperitoneally [i.p.]) and remained decreased 24 hours later in P2 fractions. Cortical Best1 levels were also reduced following 1.5 g/kg. However, CAAC expression was unaltered in the striatum following a single ethanol exposure. Ethanol did not affect Tweety2 levels in either brain region. CONCLUSIONS: These results suggest that CAACs are a major target of ethanol in vivo, and the regulation of these channels contributes to select behavioral actions of ethanol. PMID- 26842251 TI - Different Hypothalamic Nicotinic alpha7 Receptor Expression and Response to Low Nicotine Dose in Alcohol-Preferring and Alcohol-Avoiding Rats. AB - BACKGROUND: The aim of this study was to examine possible differences in nicotinic acetylcholine receptors and responses in rats with genetic preference or avoidance for alcohol. This was done by using 2 rat lines with high alcohol preference (Alko Alcohol [AA]) or alcohol avoidance (Alko Non-Alcohol [ANA]). METHODS: Locomotor activity was measured following nicotine and histamine H3 receptor (H3R) antagonist treatment. In situ hybridization and receptor ligand binding experiments were used in drug-naive animals to examine the expression of different alpha nicotinic receptor subunits. RESULTS: The AA rats were found to be more sensitive to the stimulatory effect of a low dose of nicotine than ANA rats, which were not significantly activated. Combination of histamine H3R antagonist, JNJ-39220675, and nicotine resulted to similar locomotor activation as nicotine alone. To further understand the mechanism underlying the difference in nicotine response in AA and ANA rats, we studied the expression of alpha5, alpha6, and alpha7 nicotinic receptor subunits in specific brain areas of AA and ANA rats. We found no differences in the expression of alpha5 nicotinic receptor subunits in the medial habenula and hippocampus or in alpha6 subunit in the ventral tegmental area and substantia nigra. However, the level of alpha7 nicotinic receptor subunit mRNA was significantly lower in the tuberomamillary nucleus of posterior hypothalamus of alcohol-preferring AA rats than in alcohol avoiding ANA rats. Also the hypothalamic [125I-alpha-bungarotoxin binding was lower in AA rats indicating lower levels of alpha7 nicotinic receptors. CONCLUSIONS: The lower expression and receptor binding of alpha7 nicotinic receptors in the tuberomamillary nucleus of AA rats suggest a difference in the regulation of brain histamine neurons between the rat lines since the alpha7 nicotinic receptors are located in histaminergic neurons. Stronger nicotine induced locomotor response, mediated partially via alpha7 receptors, and previously described high alcohol consumption in AA rats could be explained by the found difference in tuberomamillary alpha7 receptor levels. PMID- 26842252 TI - The Circadian Clock Mutation Promotes Intestinal Dysbiosis. AB - BACKGROUND: Circadian rhythm disruption is a prevalent feature of modern day society that is associated with an increase in pro-inflammatory diseases, and there is a clear need for a better understanding of the mechanism(s) underlying this phenomenon. We have previously demonstrated that both environmental and genetic circadian rhythm disruption causes intestinal hyperpermeability and exacerbates alcohol-induced intestinal hyperpermeability and liver pathology. The intestinal microbiota can influence intestinal barrier integrity and impact immune system function; thus, in this study, we sought to determine whether genetic alteration of the core circadian clock gene, Clock, altered the intestinal microbiota community. METHODS: Male Clock(Delta19) -mutant mice (mice homozygous for a dominant-negative-mutant allele) or littermate wild-type mice were fed 1 of 3 experimental diets: (i) a standard chow diet, (ii) an alcohol containing diet, or (iii) an alcohol-control diet in which the alcohol calories were replaced with dextrose. Stool microbiota was assessed with 16S ribosomal RNA gene amplicon sequencing. RESULTS: The fecal microbial community of Clock-mutant mice had lower taxonomic diversity, relative to wild-type mice, and the Clock(Delta19) mutation was associated with intestinal dysbiosis when mice were fed either the alcohol-containing or the control diet. We found that alcohol consumption significantly altered the intestinal microbiota in both wild-type and Clock-mutant mice. CONCLUSIONS: Our data support a model by which circadian rhythm disruption by the Clock(Delta19) mutation perturbs normal intestinal microbial communities, and this trend was exacerbated in the context of a secondary dietary intestinal stressor. PMID- 26842253 TI - The Influence of Extrinsic Reinforcement on Children with Heavy Prenatal Alcohol Exposure. AB - BACKGROUND: Prenatal alcohol exposure affects inhibitory control and other aspects of attention and executive function. However, the efficacy of extrinsic reinforcement on these behaviors has not been tested. METHODS: Alcohol-exposed children (AE; n = 34), children with attention-deficit/hyperactivity disorder (ADHD; n = 23), and controls (CON; n = 31) completed a flanker task with 4 reward conditions (no reward, reward, reward+occasional response cost, equal probability of reward+response cost). Inhibitory control was tested in the no reward conditions using a 3(group) * 2(flanker type) ANCOVA. Response to reinforcement was tested using 3(group) * 4(reward condition) * 4(flanker type) analysis of covariance (ANCOVA). Response time (RT) and accuracy were tested independently. RESULTS: Groups did not differ on demographic variables. The flanker task was successful in taxing interference control, an aspect of executive attention (i.e., responses to incongruent stimuli were slower than to congruent stimuli) and the AE group demonstrated impaired executive control over the other groups. Overall, the AE group had significantly slower RTs compared to the CON and ADHD groups, which did not differ. However, reinforcement improved RT in all groups. While occasional response cost had the greatest benefit in the CON group, the type of reinforcement did not differentially affect the AE and ADHD groups. Accuracy across reward conditions did not differ by group, but was dependent on flanker type and reward condition. CONCLUSIONS: Alcohol-exposed children, but not children with ADHD, had impaired interference control in comparison with controls, supporting a differential neurobehavioral profile in these 2 groups. Both clinical groups were equally affected by introduction of reinforcement, although the type of reinforcement did not differentially affect performance as it did in the control group, suggesting that reward or response cost could be used interchangeably to result in the same benefit. PMID- 26842254 TI - Racial/Ethnic Differences in the Prevalence of Clinically Recognized Alcohol Use Disorders Among Patients from the U.S. Veterans Health Administration. AB - BACKGROUND: Alcohol use disorders (AUDs) are common and have worse consequences for racial/ethnic minority groups than whites. AUDs are often underrecognized in clinical settings, but it is unknown whether the prevalence of clinically recognized AUD varies across racial/ethnic groups. We describe the overall and age- and gender-stratified prevalence of clinically documented AUD across 3 racial/ethnic groups in a national sample of Veterans Health Administration (VA) patients. METHODS: Data from VA's National Patient Care Database identified all patients who used VA care in Fiscal Year 2012 and were documented as black, Hispanic, or white race/ethnicity. The prevalence of clinically recognized AUD based on ICD-9 diagnoses was compared across racial/ethnic groups overall and within gender and age groups using chi-square tests of independence. RESULTS: Among 4,666,403 eligible patients, 810,902 (17.4%) were black, 302,331 (6.5%) were Hispanic, and 3,553,170 (76.1%) were white. The prevalence of clinically recognized AUD was 6.5% overall, and 9.8% (95% CI 9.8 to 9.9) among black, 7.1% (95% CI 7.0 to 7.2) among Hispanic, and 5.7% (95% CI 5.6 to 5.7) among white patients (p < 0.001). This pattern generally held for men, regardless of age group, with the exception of those 18 to 29 years old, for whom no difference was observed across race/ethnicity. Among women, the prevalence of AUD was generally lowest among Hispanic and highest among black patients, with the exception of those 30 to 44 years old, for whom the highest prevalence was among whites. CONCLUSIONS: In contrast to findings from the general population, the prevalence of clinically recognized AUD among VA patients is generally highest among black men and women and lowest among white men and Hispanic women. This is the first study to describe the prevalence of clinically recognized AUD across racial/ethnic groups in a large healthcare system. Future research comparing estimates to diagnoses based on structured gold-standard assessments is needed to understand whether AUDs are under- or overidentified. PMID- 26842255 TI - Theory of Mind in Children with Fetal Alcohol Spectrum Disorders. AB - BACKGROUND: Theory of mind (ToM) refers to the ability to understand and make inferences about other people's intentions, feelings, and beliefs. Although children with fetal alcohol spectrum disorders (FASD) are known to have deficits in social-cognitive function, little is known about ToM in FASD. METHODS: ToM ability was assessed using a developmentally sensitive ToM battery, including the reading the mind in the eyes (RME) test, a measure of mental inferential ability that has been found to be impaired in other clinical populations. IQ and executive function (EF) were assessed as potential mediating variables. The battery was administered to 63 children (aged 9 to 11 years) from Cape Town, South Africa, whose mothers had been prospectively recruited during pregnancy. Children with fetal alcohol syndrome (FAS; n = 8) and partial FAS (PFAS; n = 19), as well as nonsyndromal heavily exposed children (n = 17), were compared to children born to abstaining or light drinkers (n = 19) from the same community. RESULTS: No FASD group differences were found on the less challenging ToM tasks. By contrast, children with FAS and PFAS performed more poorly than controls on a more challenging ToM task, the RME test. A continuous measure of prenatal alcohol exposure (PAE) was more sensitive than FASD diagnosis in that it was related to 4 higher-order ToM measures, particularly the ability to attribute mental states assessed on RME. IQ only partially mediated the effect of exposure on RME performance, and these effects were not mediated by EF. Hence, the data suggest that these ToM measures tap into a specific alcohol-related social-cognitive deficit that does not merely reflect poorer EF. FASD diagnosis and PAE were each also related to RME after control for attention deficit/hyperactivity disorder. CONCLUSIONS: These findings suggest that deficits in higher-order ToM function may play a significant role in the social-cognitive behavioral impairment in FASD. PMID- 26842257 TI - Policy-Relevant Behaviors Predict Heavier Drinking in Both On and Off Premises and Mediate the Relationship Between Heavier Alcohol Consumption and Age, Gender, and Socioeconomic Status-Analysis from the International Alcohol Control Study. AB - BACKGROUND: Our goal was to investigate the role of behaviors amenable to policy change in mediating the relationship between alcohol consumption in off and on premises, age, and 2 measures of socioeconomic status (education and income). METHODS: A cross-sectional general population survey was analyzed by using Bayesian path analysis to understand direct and mediating pathways. A total of 1,900 drinkers (past 6 months), aged 18 to 65 years, living in households with landline phones participated in the study. Measures were as follows: typical quantities of alcohol consumed per occasion, frequency of drinking, both off and on premise; gender, age groups; and years of education, personal income, prices paid, time of purchase, and liking for alcohol advertisements. RESULTS: Later times of purchase predicted larger quantities consumed (on and off premise) and more frequent drinking (on premise only). Younger people and males purchased later, and this mediated their heavier consumption. Lower prices paid predicted larger quantities consumed (on premise) and higher frequency of drinking (off premise). Younger and male respondents paid lower prices, and this mediated larger quantities consumed on premise and more frequent drinking off premise. Less well educated paid lower prices, and this mediated drinking more frequently off premise among this group. Liking for alcohol ads predicted drinking larger quantities and higher frequency both off and on premise. Younger and male respondents reported greater liking for ads, and this mediated their consumption of larger quantities and more frequent drinking both on and off premise. Those with higher income drank larger amounts on premise and more frequently on and off, but there were no mediating effects from the policy-relevant variables. CONCLUSIONS: Heavier drinking patterns by young people and those less well educated could be ameliorated by attention to alcohol policy. PMID- 26842256 TI - Alcohol Consumption and Risk for Dependence Among Male Latino Migrant Farmworkers Compared to Latino Nonfarmworkers in North Carolina. AB - BACKGROUND: Our aim was to describe alcohol consumption behavior of male Latino migrant farmworkers, compare their alcohol consumption behavior with that of other male Latino immigrants, and determine factors associated with risk for alcohol dependence among Latino immigrant workers. METHODS: Cross-sectional data were drawn from baseline interviews conducted as part of a larger community-based participatory research project examining the cognitive and neurological outcomes of pesticide exposure. A total of 235 farmworkers and 212 nonfarmworkers completed interviews between May and August 2012. RESULTS: Although 17.5% of the North Carolina Latino farmworkers report never having drunk alcohol, and a total of 34.5% report not having drunk alcohol in the previous 3 months, 48.5% engaged in heavy episodic drinking (HED) in the previous 3 months, and 23.8% frequently engaged in HED during this period. Farmworkers and nonfarmworkers did not differ significantly in alcohol consumption behavior. Farmworkers and nonfarmworkers did differ significantly in each component of the CAGE scale, with 37.9% of farmworkers and 16.0% of nonfarmworkers being at risk for alcohol dependence (p < 0.0001). Significant factors for being at risk for alcohol dependence were stress (odds ratio 1.06, 95% confidence interval 1.03, 1.09) and being a farmworker (odds ratio 3.58, 95% confidence interval 2.12, 6.06). Being married reduced the risk of alcohol dependence (odds ratio 0.45, 95% confidence interval 0.23, 0.87). CONCLUSIONS: Latino farmworkers and nonfarmworkers consume relatively large amounts of alcohol and engage in HED at relatively high rates. Latino farmworkers have very high rates of risk for alcohol dependence. Policy changes and public health interventions are needed to address these concerns for a population that is vital to the agricultural economy. PMID- 26842258 TI - Gender-Specific Effects of Mood on Alcohol-Seeking Behaviors: Preliminary Findings Using Intravenous Alcohol Self-Administration. AB - BACKGROUND: Although negative mood has long been implicated in differences in alcohol seeking by men and women, little research has used precise, well controlled laboratory experiments to examine how negative mood affects alcohol seeking behaviors. METHODS: A total of 34 (19 women) community-dwelling, alcohol using adults aged 21 to 32 (mean age = 24.86, SD = 3.40, 74.3% Caucasian; Alcohol Use Disorders Identification Test [AUDIT] = 10.1, SD = 3.4) completed 2 counterbalanced intravenous alcohol self-administration sessions: one under negative mood and one under neutral mood. Fourteen individuals (9 women; mean age = 25.00, SD = 2.77) participated in an alcohol "liking" experiment (i.e., free access [FA] drinking) and 20 individuals (10 women; mean age = 24.77, SD = 3.73) participated in an alcohol "wanting" experiment, in which gaining access to alcohol required progressively effortful work. There was no significant difference between men and women on the AUDIT, t(32) = -0.38, p = 0.71. RESULTS: Priming with negative mood induction caused a significant decrease in self reported mood (mean change = -1.85, t(32) = -6.81, p < 0.001), as intended. In FA, negative mood was associated with a significantly increased peak breath alcohol concentration (BrAC; F = 9.41, p = 0.01), with a trend toward a greater effect in men than in women (F = 2.67, p = 0.13). Negative mood also had a significant effect on peak BrAC achieved in the progressive work paradigm (F = 5.28, p = 0.04), with a significantly stronger effect in men (F = 5.35, p = 0.03) than women; men also trended toward more consistent work for alcohol across both neutral and negative sessions. CONCLUSIONS: These preliminary findings demonstrate a gender-specific response on how mood affects alcohol seeking and suggest gender-specific interventions to prevent mood-based alcohol consumption. PMID- 26842259 TI - The Polish Version of the Yale-Brown Obsessive-Compulsive Scale, Modified to Reflect Obsessions and Compulsions Related to Heavy Drinking (YBOCS-hd-PL). AB - BACKGROUND: The aim of the research work was to present the process of adapting the Polish version of the YBOCS-hd by Modell and colleagues (Alcohol Clin Exp Res 1992;16:266) to Polish conditions and to characterize the psychometric validation of the measure (e.g., validity, internal structure, and reliability). The scale is a self-assessment method consisting of 10 statements designed for measuring the severity of obsessive and compulsive craving-related thoughts and behaviors in alcohol-dependent or alcohol-abusing patients. METHODS: The study was carried out in a group of 550 patients diagnosed with alcohol dependence syndrome, 510 of whom (396 males and 114 females) were included in the final analysis. The patients were interviewed during the third week of therapy by the Polish version of the Yale-Brown Compulsive Scale Modified to Reflect Obsessions and Compulsions Related to Heavy Drinking (YBOCS-hd-PL), the Penn Alcohol Craving Scale (PACS), Short Alcohol Dependence Data Questionnaire (SADD), and the "compulsive" subscale of SCL-90. RESULTS: The YBOCS-hd-PL is characterized by good psychometric properties. Factor analysis identified 2 factors corresponding to the structure of the original version. Its internal consistency, assessed on the basis of Cronbach's alpha, is satisfactory: 0.84 for YBOCS-hd-PL (overall), 0.75 for factor 1 (obsessive thoughts), and 0.79 for factor 2 (compulsive behaviors). The discriminant power of the questions ranged from 0.46 to 0.68 (p < 0.001). For the adapted YBOCS-hd-PL, significant correlations were found between its scores and the PACS and the "compulsive" subscale of the SCL-90 scale. The obtained results indicate the Polish version of the YBOCS-hd (YBOCS-hd-PL) proved to be a reliable and valid instrument. CONCLUSIONS: In view of its very good psychometric properties, the Polish version of the YBOCS-hd can be recommended as an instrument for assessment of alcohol craving and its obsessive and compulsive aspects in individuals with alcohol use disorders. PMID- 26842260 TI - Hospital Stay and Engagement in Outpatient Follow-Up After Alcohol Emergency Detox: A 1-Year Comparison Study. AB - BACKGROUND: Inpatient alcohol detoxifications are only proposed after motivational outpatient encounters because detoxification directly from the emergency department (ED) is believed to be associated with early dropout and poor adherence to outpatient follow-up. The aim of this prospective follow-up study was to test the feasibility of unscheduled (UP) alcohol detoxification directly from the ED and to compare the 1-year follow-up of these patients to that of scheduled (SP) patients. METHODS: A quasi-naturalistic prospective follow up study of 120 patients: 60 consecutively admitted patients referred directly by the ED for alcohol detoxification (UP) were compared to 60 consecutively admitted patients who had undergone the usual preparation for an inpatient detoxification program (SP). The length of hospitalization (in days) and attendance to postdischarge outpatient visits during the first year was compared. RESULTS: UP patients were older, less frequently employed, and had more somatic comorbidities compared with SP patients. The UP length of stay was significantly longer (20 +/- 16 vs. 14 +/- 6, p = 0.04). No difference in their postdischarge attendance was observed; the number of patients attending 1 session (57% UP vs. 65% SP, p = 0.227) and 5 sessions (22% UP vs. 32% SP, p = 0.151) and the mean number of postdischarge visits attended were comparable between the UP and SP groups (2.7 +/- 6 vs. 4.5 +/- 6; Mann-Whitney U = 1,517, p = 0.124). CONCLUSIONS: We did not find that UP patients who had been admitted for alcohol detoxification had a significantly higher dropout rate or lower postdischarge addiction treatment attendance. Because they may have several advantages, detoxification programs directly linked with EDs should be further evaluated. PMID- 26842261 TI - Dynamic Exposure to Alcohol Advertising in a Sports Context Influences Implicit Attitudes. AB - BACKGROUND: Experimental studies investigating the impact of advertising with ecological stimuli on alcohol-related cognition are scarce. This research investigated the cognitive processes involved in learning implicit attitudes toward alcohol after incidental exposure to alcohol advertisements presented in a dynamic context. We hypothesized that incidental exposure to a specific alcohol brand would lead to heightened positive implicit attitudes toward alcohol due to a mere exposure effect. METHODS: In total, 108 participants were randomly exposed to dynamic sporting events excerpts with and without advertising for a specific brand of alcohol, after completing self-reported measures of alcohol-related expectancies, alcohol consumption, and attitudes toward sport. Participants then completed a lexical decision task and an affective priming task. RESULTS: We showed that participants were faster to detect brand name after being exposed to advertising during a sports game, and that implicit attitudes of participants toward the brand were more positive after they were exposed to advertising, even when alcohol usage patterns were controlled for. CONCLUSIONS: Incidental exposure to alcohol sponsorship in sport events impacts implicit attitudes toward the advertised brand and alcohol in general. The effect of incidental advertising on implicit attitudes is also likely to be due to a mere exposure effect. However, further studies should address this point specifically. PMID- 26842262 TI - Cognitive Control Over Immediate Reward in Binge Alcohol Drinkers. AB - BACKGROUND: Cognitive control deficits, as captured by inhibitory control measures, are indicative of increased impulsivity and are considered a marker for substance use disorder vulnerability. While individuals with alcohol use disorder (AUD) typically exhibit inhibitory control dysfunction, evidence of impaired inhibitory control among harmful drinkers, who are at increased risk of developing an AUD, is mixed. This study examined the response inhibition of binge drinkers using a task that employed neutral, as well as both immediate and delayed reward contingencies, to determine whether reward induced heightened impulsivity in this population. METHODS: Binge alcohol users (n = 42) and controls (n = 42) were administered a Monetary Incentive Control Task that required participants to successfully inhibit a prepotent motor response to both neutral and immediately rewarding stimuli in order to secure a large delayed reward. RESULTS: Binge drinkers had significantly worse response inhibition than controls irrespective of trial condition and even after controlling for differences in weekly intake. Although both binge and control participants exhibited significantly worse inhibitory control in the presence of immediate reward, the control group showed a greater reduction in inhibition accuracy compared to the binge group in reward relative to neutral conditions. Both groups demonstrated significantly enhanced control when forewarned there was an increased chance response inhibition would be required. Control participants secured the delayed reward more often than binge participants. CONCLUSIONS: Despite the variability in the literature, this study demonstrated consistent generalized impulse control deficits among binge-drinking individuals that were unrelated to reward manipulations. These findings point to mechanisms that may confer vulnerability for transition from binge drinking to AUD. PMID- 26842264 TI - Multipartite entanglement indicators based on monogamy relations of n-qubit symmetric states. AB - Constructed from Bai-Xu-Wang-class monogamy relations, multipartite entanglement indicators can detect the entanglement not stored in pairs of the focus particle and the other subset of particles. We investigate the k-partite entanglement indicators related to the alphath power of entanglement of formation (alphaEoF) for k <= n, alphaepsilon and n-qubit symmetric states. We then show that (1) The indicator based on alphaEoF is a monotonically increasing function of k. (2) When n is large enough, the indicator based on alphaEoF is a monotonically decreasing function of alpha, and then the n-partite indicator based on works best. However, the indicator based on 2 EoF works better when n is small enough. PMID- 26842265 TI - Molecular Actions of Glucocorticoids in Cartilage and Bone During Health, Disease, and Steroid Therapy. AB - Cartilage and bone are severely affected by glucocorticoids (GCs), steroid hormones that are frequently used to treat inflammatory diseases. Major complications associated with long-term steroid therapy include impairment of cartilaginous bone growth and GC-induced osteoporosis. Particularly in arthritis, GC application can increase joint and bone damage. Contrarily, endogenous GC release supports cartilage and bone integrity. In the last decade, substantial progress in the understanding of the molecular mechanisms of GC action has been gained through genome-wide binding studies of the GC receptor. These genomic approaches have revolutionized our understanding of gene regulation by ligand induced transcription factors in general. Furthermore, specific inactivation of GC signaling and the GC receptor in bone and cartilage cells of rodent models has enabled the cell-specific effects of GCs in normal tissue homeostasis, inflammatory bone diseases, and GC-induced osteoporosis to be dissected. In this review, we summarize the current view of GC action in cartilage and bone. We further discuss future research directions in the context of new concepts for optimized steroid therapies with less detrimental effects on bone. PMID- 26842266 TI - Pesticide analysis using nanoceria-coated paper-based devices as a detection platform. AB - We report the first use of a paper-based device coated with nanoceria as a simple, low-cost and rapid detection platform for the analysis of organophosphate (OP) pesticides using an enzyme inhibition assay with acetylcholinesterase (AChE) and choline oxidase (ChOX). In the presence of acetylcholine, AChE and ChOX catalyze the formation of H2O2, which is detected colorimetrically by a nanoceria coated device resulting in the formation of a yellow color. After incubation with OP pesticides, the AChE activity was inhibited, producing less H2O2, and a reduction in the yellow intensity. The assay is able to analyze OP pesticides without the use of sophisticated instruments and gives detection limits of 18 ng mL(-1) and 5.3 ng mL(-1) for methyl-paraoxon and chlorpyrifos-oxon, respectively. The developed method was successfully applied to detect methyl-paraoxon in spiked vegetables (cabbage) and a dried seafood product (dried green mussel), obtaining ~95% recovery values for both sample types. The spiked samples were also analyzed using LC-MS/MS as a comparison to the developed method and similar values were obtained, indicating that the developed method gives accurate results and is suitable for OP analysis in real samples. PMID- 26842267 TI - Open access resources for genome-wide association mapping in rice. AB - Increasing food production is essential to meet the demands of a growing human population, with its rising income levels and nutritional expectations. To address the demand, plant breeders seek new sources of genetic variation to enhance the productivity, sustainability and resilience of crop varieties. Here we launch a high-resolution, open-access research platform to facilitate genome wide association mapping in rice, a staple food crop. The platform provides an immortal collection of diverse germplasm, a high-density single-nucleotide polymorphism data set tailored for gene discovery, well-documented analytical strategies, and a suite of bioinformatics resources to facilitate biological interpretation. Using grain length, we demonstrate the power and resolution of our new high-density rice array, the accompanying genotypic data set, and an expanded diversity panel for detecting major and minor effect QTLs and subpopulation-specific alleles, with immediate implications for rice improvement. PMID- 26842268 TI - Cannabinoid hyperemesis syndrome masquerading as an eating disorder. AB - The case of a 22 year old woman with cannabinoid hyperemesis syndrome (CHS) presenting as an eating disorder is described. The importance of recognizing chronic cannabis use as a cause of episodic vomiting is emphasized, given that CHS can be confused with self-induced purging and cyclic vomiting. This case was further complicated by the well-defined history of anorexia nervosa (binge-purge type), major depressive disorder, obsessive-compulsive disorder, migraine headache, and the initial denial of cannabis use. However, collateral history and a positive drug screen confirmed the diagnosis. The signs, symptoms and pathophysiological mechanisms of CHS are reviewed in light of clinical presentations that mimic eating disorder phenomenology complicated by addiction. Given the trend for increasing legalization of recreational marijuana as well as medical marijuana, CHS is an important and potentially complicating disorder that eating disorder clinicians need to be aware of. (c) 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:826-829). PMID- 26842269 TI - Evaluation of quantum dot immunofluorescence and a digital CMOS imaging system as an alternative to conventional organic fluorescence dyes and laser scanning for quantifying protein microarrays. AB - Organic fluorescent dyes are widely used for the visualization of bound antibody in a variety of immunofluorescence assays. However, the detection equipment is often expensive, fragile, and hard to deploy widely. Quantum dots (Qdot) are nanocrystals made of semiconductor materials that emit light at different wavelengths according to the size of the crystal, with increased brightness and stability. Here, we have evaluated a small benchtop "personal" optical imager (ArrayCAM) developed for quantification of protein arrays probed by Qdot-based indirect immunofluorescence. The aim was to determine if the Qdot imager system provides equivalent data to the conventional organic dye-labeled antibody/laser scanner system. To do this, duplicate proteome microarrays of Vaccinia virus, Brucella melitensis and Plasmodium falciparum were probed with identical samples of immune sera, and IgG, IgA, and IgM profiles visualized using biotinylated secondary antibodies followed by a tertiary reagent of streptavidin coupled to either P3 (an organic cyanine dye typically used for microarrays) or Q800 (Qdot). The data show excellent correlation for all samples tested (R > 0.8) with no significant change of antibody reactivity profiles. We conclude that Qdot detection provides data equivalent to that obtained using conventional organic dye detection. The portable imager offers an economical, more robust, and deployable alternative to conventional laser array scanners. PMID- 26842270 TI - Effect of telehealth on hospital utilisation and mortality in routine clinical practice: a matched control cohort study in an early adopter site. AB - OBJECTIVES: To assess the effects of a home-based telehealth intervention on the use of secondary healthcare and mortality. DESIGN: Observational study of a mainstream telehealth service, using person-level administrative data. Time to event analysis (Cox regression) was performed comparing telehealth patients with controls who were matched using a machine-learning algorithm. SETTING: A predominantly rural region of England (North Yorkshire). PARTICIPANTS: 716 telehealth patients were recruited from community, general practice and specialist acute care, between June 2010 and March 2013. Patients had chronic obstructive pulmonary disease, congestive heart failure or diabetes, and a history of associated inpatient admission. Patients were matched 1:1 to control patients, also selected from North Yorkshire, with respect to demographics, diagnoses of health conditions, previous hospital use and predictive risk score. INTERVENTIONS: Telehealth involved the remote exchange of medical data between patients and healthcare professionals as part of the ongoing management of the patient's health condition. Monitoring centre staff alerted healthcare professionals if the telemonitored data exceeded preset thresholds. Control patients received usual care, without telehealth. PRIMARY AND SECONDARY OUTCOME MEASURES: Time to the first emergency (unplanned) hospital admission or death. Secondary metrics included time to death and time to first admission, outpatient attendance and emergency department visit. RESULTS: Matched controls and telehealth patients were similar at baseline. Following enrolment, telehealth patients were more likely than matched controls to experience emergency admission or death (adjusted HR 1.34, 95% CI 1.16 to 1.56, p<0.001). They were also more likely to have outpatient attendances (adjusted HR=1.25, 1.11 to 1.40, p<0.001), but mortality rates were similar between groups. Sensitivity analyses showed that we were unlikely to have missed reductions in the likelihood of an emergency admission or death because of unobserved baseline differences between patient groups. CONCLUSIONS: Telehealth was not associated with a reduction in secondary care utilisation. PMID- 26842271 TI - Development of a Health Empowerment Programme to improve the health of working poor families: protocol for a prospective cohort study in Hong Kong. AB - INTRODUCTION: People from working poor families are at high risk of poor health partly due to limited healthcare access. Health empowerment, a process by which people can gain greater control over the decisions affecting their lives and health through education and motivation, can be an effective way to enhance health, health-related quality of life (HRQOL), health awareness and health seeking behaviours of these people. A new cohort study will be launched to explore the potential for a Health Empowerment Programme to enable these families by enhancing their health status and modifying their attitudes towards health related issues. If proven effective, similar empowerment programme models could be tested and further disseminated in collaborations with healthcare providers and policymakers. METHOD AND ANALYSIS: A prospective cohort study with 200 intervention families will be launched and followed up for 5 years. The following inclusion criteria will be used at the time of recruitment: (1) Having at least one working family member; (2) Having at least one child studying in grades 1-3; and (3) Having a monthly household income that is less than 75% of the median monthly household income of Hong Kong families. The Health Empowerment Programme that will be offered to intervention families will comprise four components: health assessment, health literacy, self-care enablement and health ambassador. Their health status, HRQOL, lifestyle and health service utilisation will be assessed and compared with 200 control families with matching characteristics but will not receive the health empowerment intervention. ETHICS AND DISSEMINATION: This project was approved by the University of Hong Kong-the Hospital Authority Hong Kong West Cluster IRB, Reference number: UW 12-517. The study findings will be disseminated through a series of peer-reviewed publications and conference presentations, as well as a yearly report to the philanthropic funding body-Kerry Group Kuok Foundation (Hong Kong) Limited. PMID- 26842273 TI - Impact of wearable technology on psychosocial factors of osteoarthritis management: a qualitative study. AB - OBJECTIVES: To identify the impact the use of wearable technology could have in patients with osteoarthritis in terms of communication with healthcare providers and patients' empowerment to manage their condition. DESIGN: Qualitative study using focus groups with patients with osteoarthritis; data from patients' responses were analysed using Framework Methodology. PARTICIPANTS: 21 patients with knee osteoarthritis from the London area (age range 45-65 years) participated in a total of four focus groups. Recruitment continued until data saturation. SETTING: The study was conducted in a university setting. RESULTS: Patients' responses suggested a positive attitude on the impact wearable technology could have on the management of osteoarthritis. It was perceived that the use of wearable devices would benefit patients in terms of feeling in control of their condition, providing them with awareness of their progress, empowering in terms of self-management and improving communication with their clinician. CONCLUSIONS: This paper suggests positive patient perspectives on the perceived benefits wearable technology could have on the management of osteoarthritis. The data that could be collected with the use of wearable technology could be beneficial both to patients and clinicians. The information obtained from this study suggests that introducing wearable technology into patient-centred care could enhance patient experience in the field of osteoarthritis and beyond. PMID- 26842272 TI - Genetics of Glucose regulation in Gestation and Growth (Gen3G): a prospective prebirth cohort of mother-child pairs in Sherbrooke, Canada. AB - PURPOSE: We initiated the Genetics of Glucose regulation in Gestation and Growth (Gen3G) prospective cohort to increase our understanding of biological, environmental and genetic determinants of glucose regulation during pregnancy and their impact on fetal development. PARTICIPANTS: Between January 2010 and June 2013, we invited pregnant women aged >= 18 years old who visited the blood sampling in pregnancy clinic in Sherbrooke for their first trimester clinical blood samples: 1034 women accepted to participate in our cohort study. FINDINGS TO DATE: At first and second trimester, we collected demographics and lifestyle questionnaires, anthropometry measures (including fat and lean mass estimated using bioimpedance), blood pressure, and blood samples. At second trimester, women completed a full 75 g oral glucose tolerance test and we collected additional blood samples. At delivery, we collected cord blood and placenta samples; obstetrical and neonatal clinical data were abstracted from electronic medical records. We also collected buffy coats and extracted DNA from maternal and/or offspring samples (placenta and blood cells) to pursue genetic and epigenetic hypotheses. So far, we have found that low adiponectin and low vitamin D maternal levels in first trimester predict higher risk of developing gestational diabetes. FUTURE PLANS: We are now in the phase of prospective follow up of mothers and offspring 3 and 5 years postdelivery to investigate the consequences of maternal dysglycaemia during pregnancy on offspring adiposity and metabolic profile. TRIAL REGISTRATION NUMBER: NCT01623934. PMID- 26842274 TI - Role of gender, family, lifestyle and psychological factors in self-rated health among urban adolescents in Peru: a school-based cross-sectional survey. AB - OBJECTIVE: We examined the role of gender, family, lifestyle and psychological factors in self-rated health. DESIGN: Cross-sectional study. SETTING: A total of 970 randomly selected students from 11 secondary schools in Lima and Callao, Peru, participated in 2014. MAIN OUTCOME MEASURE: Self-rated health was measured with a single item: 'In general, how would you rate your health?' Responses were arranged along a five-point Likert-type scale: 'excellent', 'very good', 'good', 'fair' and 'poor'. The outcome variable was dichotomised as 'good' (excellent, very good or good) or 'poor/fair' (poor or fair). METHODS: We calculated adjusted ORs (AORs) and 95% CIs for poor/fair self-rated health using multivariate logistic regression analyses at 3-graded levels. RESULTS: 32.5% of the respondents had fair/poor self-rated health, 23.7% of the total males and 40.0% of the total female samples. Males were less likely to have poor/fair self-rated health (AOR 0.61; CI 0.41 to 0.91). Poor family support strongly increased the likelihood of having poor/fair self-rated health (no support, (AOR 3.15; CI 1.63 to 6.09); low support, (AOR 2.50; CI 1.29 to 4.85)). The other associated variables were missed meals due to a shortage of food (AOR 1.97; CI 1.15 to 3.36), television watching during leisure time (AOR 1.70; CI 1.09 to 2.67), low physical activity (AOR 1.49; CI 1.03 to 2.15), school absenteeism (AOR 1.54; CI 1.03 to 2.31) and perceived life satisfaction (AOR 0.28; CI 0.15 to 0.25). CONCLUSIONS: Gender, missing meals due to a shortage of food, family support, physical activity and life satisfaction influenced self-rated health among adolescents in Peru. Interventions that focus on promoting physical activity for at least 1 h each day for 3 or more days per week, food security and strengthening supportive family roles may improve self-rated health during adolescence. PMID- 26842275 TI - Understanding and evaluating the effects of implementing an electronic paediatric prescribing system on care provision and hospital work in paediatric hospital ward settings: a qualitatively driven mixed-method study protocol. AB - INTRODUCTION: Electronic prescribing systems can improve the quality and safety of healthcare services, but their implementation is not straightforward and may create unexpected change. However, the added complexity of paediatric prescribing (eg, dose calculations, dilutions, manipulations) may pose additional challenges. This study will aim to (1) understand the complex organisational reality of a paediatric hospital in which a new electronic paediatric prescribing (ePP) system will be introduced; (2) describe ePP-related change, over time, in paediatric hospital ward settings; (3) explore staff perspectives in relation to currently established practices and processes; and (4) assess the impact of ePP on care provision and hospital work from the perspective of paediatricians, paediatric nurses and managers. METHODS AND ANALYSIS: A qualitatively driven mixed-method approach will be adopted, including 3 inter-related substudies. The core component of the study will be qualitative (substudy 1): we will use ethnographic research methods, including non-participant observation in wards and informal conversational interviews with members of staff. In addition, the design will include 2 embedded supplementary components: a qualitative 1 (substudy 2) based on in-depth interviews and/or focus groups with paediatricians, paediatric nurses, paediatric pharmacists/pharmacy technicians and managers; and a quantitative 1 (substudy 3) in which a staff survey will be developed and administered before and after the ePP implementation. Analytic themes will be identified from ethnographic field notes and interview data. Survey data will be analysed using descriptive statistics and baseline and follow-up data compared to establish impact evaluation measures. ETHICS AND DISSEMINATION: A favourable ethical opinion has been obtained from a National Health Service (NHS) Research Ethics Committee (15/SS/0157). NHS research governance approval has been obtained at the relevant hospital site. The results of the study will be disseminated through conferences and peer-reviewed journals, as well as fed back to those involved in clinical practice and policy development at the study site. PMID- 26842277 TI - Child health in China: great progress but challenges ahead. PMID- 26842278 TI - Gun violence in America: a national crisis. PMID- 26842276 TI - Obesity: we need to move beyond sugar. PMID- 26842279 TI - Death and planetary health. PMID- 26842280 TI - Ombudsman's report for 2015. PMID- 26842281 TI - In appreciation of the peer-review heroes from 2015. PMID- 26842282 TI - The historian will see you now: introducing Case Histories. PMID- 26842284 TI - Global Fund plays hard ball on corruption. PMID- 26842285 TI - In Papua New Guinea, HIV/AIDS-related stigma is still rife. PMID- 26842286 TI - Parkinson's disease. PMID- 26842288 TI - Mary Bassett: trailblazer for health in New York City. PMID- 26842289 TI - Medicinal plants--the next generation. PMID- 26842290 TI - Alisha Lee. PMID- 26842291 TI - Neglected tropical diseases in the Sustainable Development Goals. PMID- 26842292 TI - Policy misperceptions and support for gun control legislation. PMID- 26842293 TI - Methadone for prisoners. PMID- 26842294 TI - Methadone for prisoners. PMID- 26842295 TI - Methadone for prisoners--Authors' reply. PMID- 26842296 TI - Ixekizumab for psoriasis. PMID- 26842297 TI - Ixekizumab for psoriasis--Authors' reply. PMID- 26842298 TI - Department of Error. PMID- 26842299 TI - Learning when (and how) to shut up: intercellular signal turnover in Xanthomonas. PMID- 26842300 TI - Developing senescence to remodel the embryo. AB - Cellular senescence is an irreversible form of cell cycle arrest that has been linked to several pathological conditions. In particular, senescence can function as a tumor suppressor mechanism, but is also thought to contribute to organismal aging. Paradoxically however, through the secretion of various factors, collectively termed the senescence-associated secretory phenotype (SASP), senescent cells can also have tumor-promoting and tissue-remodeling functions. In addition, senescent cells can play beneficial roles in tissue repair and wound healing, and reconciling these contradictory features from an evolutionary standpoint has been challenging. Moreover, senescent cells had not previously been documented in non-pathological conditions. Recently however, 2 studies have identified cellular senescence as a programmed mechanism that contributes to tissue patterning and remodeling during normal embryonic development. These findings have significant implications for our understanding of cellular senescence and help to clarify the paradoxes and the evolutionary origin of this process. PMID- 26842301 TI - Late-onset disease is associated with a mild phenotype in children with familial Mediterranean fever. AB - Familial Mediterranean fever (FMF) is an autosomal recessive disease, characterised by recurrent, self-limited attacks of fever with serositis. Recently, it was shown that patients with early disease onset during childhood period had more severe disease. The aim of this study was to describe the demographic, clinical and genetic features of FMF patients who had late-onset disease during childhood period and to compare them to those with earlier onset patients. Files of patients who had been seen in our department between January 2013 and January 2014 were retrospectively evaluated. Patients were divided into two groups according to age of disease onset (group I, <=8 years; group II, >8 years), and clinical findings were compared between the two groups. The study group comprised 317 FMF patients. There were 267 patients in group I and 50 patients in Group II. Median attack frequency was 24/year in group I and 12/year in group II (p < 0.05). Fever and M694V homozygosity were less frequently detected in group II (p = 0.003 and p = 0.022). Median delay in diagnosis was 24 months in group I and 12 months in group II (p = 0.002). Disease severity scores and final colchicine dosages were lower in group II (p < 0.001 and p = 0.003). Only a small number of FMF patients had disease onset at older ages in childhood period. It seems that FMF patients with late-onset disease have milder illness. However, more readily expression of their clinical findings in older ages yields earlier diagnosis in this group. PMID- 26842303 TI - Spinal cord injury affects the interplay between visual and sensorimotor representations of the body. AB - The brain integrates multiple sensory inputs, including somatosensory and visual inputs, to produce a representation of the body. Spinal cord injury (SCI) interrupts the communication between brain and body and the effects of this deafferentation on body representation are poorly understood. We investigated whether the relative weight of somatosensory and visual frames of reference for body representation is altered in individuals with incomplete or complete SCI (affecting lower limbs' somatosensation), with respect to controls. To study the influence of afferent somatosensory information on body representation, participants verbally judged the laterality of rotated images of feet, hands, and whole-bodies (mental rotation task) in two different postures (participants' body parts were hidden from view). We found that (i) complete SCI disrupts the influence of postural changes on the representation of the deafferented body parts (feet, but not hands) and (ii) regardless of posture, whole-body representation progressively deteriorates proportionally to SCI completeness. These results demonstrate that the cortical representation of the body is dynamic, responsive, and adaptable to contingent conditions, in that the role of somatosensation is altered and partially compensated with a change in the relative weight of somatosensory versus visual bodily representations. PMID- 26842302 TI - Interleukin-6 predicts inflammation-induced increase of Glucagon-like peptide-1 in humans in response to cardiac surgery with association to parameters of glucose metabolism. AB - OBJECTIVE: Glucagon-like peptide-1 (GLP-1) is an incretin hormone, which gets secreted in response to nutritional stimuli from the gut mediating glucose dependent insulin secretion. Interestingly, GLP-1 was recently found to be also increased in response to inflammatory stimuli in an interleukin 6 (IL-6) dependent manner in mice. The relevance of this finding to humans is unknown but has been suggested by the presence of high circulating GLP-1 levels in critically ill patients that correlated with markers of inflammation. This study was performed to elucidate, whether a direct link exists between inflammation and GLP 1 secretion in humans. RESEARCH DESIGN AND METHODS: We enrolled 22 non-diabetic patients scheduled for cardiac surgery as a reproducible inflammatory stimulus with repeated blood sampling before and after surgery. RESULTS: Mean total circulating GLP-1 levels significantly increased in response to surgery from 25.5 +/- 15.6 pM to 51.9 +/- 42.7 pM which was not found in a control population. This was preceded by an early rise of IL6, which was significantly associated with GLP 1 under inflammatory but not basal conditions. Using repeated measure ANCOVA, IL6 best predicted the observed kinetics of GLP-1, followed by blood glucose concentrations and cortisol plasma levels. Furthermore, GLP-1 plasma concentrations significantly predicted endogenous insulin production as assessed by C-peptide concentrations over time, while an inverse association was found for insulin infusion rate. CONCLUSION: We found GLP-1 secretion to be increased in response to inflammatory stimuli in humans, which was associated to parameters of glucose metabolism and best predicted by IL6. PMID- 26842305 TI - Metal-organic gel templated synthesis of magnetic porous carbon for highly efficient removal of organic dyes. AB - Magnetic porous carbon composites are promising materials in various applications, such as adsorbents, supercapacitors and catalyst supports, due to their high surface area, thermal and chemical stability, and easy separation. However, despite the increasing number of reports of magnetic porous carbon composites, the preparation of these materials with environmentally friendly procedures still remains a great challenge. Herein, we report a facile method to prepare a magnetic porous carbon composite with high surface area from a Fe-based metal-organic gel (MOG) template, an extended structure of a metal-organic framework (MOF). The obtained magnetic porous carbon composite was applied to remove organic dyes from an aqueous solution by selecting methyl orange (MO) as a model molecule. It exhibits excellent adsorption capacity (182.82 mg g(-1)), fast adsorption kinetics (8.13 * 10(-3) g mg(-1) min(-1)), and a perfect magnetic separation performance for the MO removal. This study demonstrates a new way to achieve clean synthesis of magnetic porous carbon materials, and opens a new door for the application of MOGs in organic dye removal. PMID- 26842306 TI - The Surgical Checklist: It Cannot Work If You Do Not Use It. PMID- 26842304 TI - Quality of life and psychological well-being in obesity management: improving the odds of success by managing distress. AB - BACKGROUND: Obesity is increasing in prevalence and placing an ever-greater burden on individuals and healthcare resources alike. Obesity management is complex and, for many, elusive. AIMS AND METHODS: This paper reviews the major factors that influence psychological well-being in individuals with obesity and describes the means by which their impact on distress and other aspects of quality of life (QoL) can be quantified. The goal is to enable healthcare providers to set reasonable, achievable, maintainable weight loss targets that will improve the psychological well-being and QoL of individuals living with obesity. PubMed and Web of Science searches were conducted to identify literature that addresses the key question: How can distress over obesity be measured and taken into account when tailoring weight loss interventions for a particular patient? DISCUSSION AND CONCLUSIONS: 'Distress over obesity' is a key parameter that illustrates the psychological consequences of excess weight. Healthcare providers can draw on a range of obesity-specific and non-specific assessment tools to quantify distress as well as the other contributions of obesity to QoL and mental/emotional health. When physicians consider the psychological/QoL aspects of obesity and how these change with successful weight loss, it becomes possible to set achievable, realistic weight loss goals and develop a manageable plan to achieve them. Any future developments that make it easier to achieve these goals should be made widely available to all patients in need, in order to help them turn a vicious cycle of failure into a virtuous cycle of success. PMID- 26842307 TI - Associations of Parental Depression With Child School Performance at Age 16 Years in Sweden. AB - IMPORTANCE: Depression is a common cause of morbidity and disability worldwide. Parental depression is associated with early-life child neurodevelopmental, behavioral, emotional, mental, and social problems. More studies are needed to explore the link between parental depression and long-term child outcomes. OBJECTIVE: To examine the associations of parental depression with child school performance at the end of compulsory education (approximately age 16 years). DESIGN, SETTING, AND PARTICIPANTS: Parental depression diagnoses (based on the International Classification of Diseases, Eighth Revision [ICD-8], International Classification of Diseases, Ninth Revision [ICD-9], and the International Statistical Classification of Diseases, 10th Revision [ICD-10]) in inpatient records from 1969 onward, outpatient records beginning in 2001, and school grades at the end of compulsory education were collected for all children born from 1984 to 1994 in Sweden. The final analytic sample size was 1,124,162 biological children. We examined the associations of parental depression during different periods (before birth, after birth, and during child ages 1-5, 6-10, and 11-16 years, as well as any time before the child's final year of compulsory schooling) with the final school grades. Linear regression models adjusted for various child and parent characteristics. The dates of the analysis were January to November 2015. MAIN OUTCOME AND MEASURE: Decile of school grades at the end of compulsory education (range, 1-10, with 1 being the lowest and 10 being the highest). RESULTS: The study cohort comprised 1,124,162 children, of whom 48.9% were female. Maternal depression and paternal depression at any time before the final compulsory school year were associated with worse school performance. After covariate adjustment, these associations decreased to -0.45 (95% CI, -0.48 to 0.42) and -0.40 (-0.43 to -0.37) lower deciles, respectively. These effect sizes are similarly as large as the observed difference in school performance between the lowest and highest quintiles of family income but approximately one-third of the observed difference between maternal education of 9 or less vs more than 12 years. Both maternal depression and paternal depression at different periods (before birth, after birth, and during child ages 1-5, 6-10, and 11-16 years) generally were associated with worse school performance. Child sex modified the associations of maternal depression with school performance such that maternal depression had a larger negative influence on child school performance for girls compared with boys. CONCLUSIONS AND RELEVANCE: Diagnoses of parental depression throughout a child's life were associated with worse school performance at age 16 years. Our results suggest that diagnoses of parental depression may have a far reaching effect on an important aspect of child development, with implications for future life course outcomes. PMID- 26842308 TI - Computational Methods for MOF/Polymer Membranes. AB - Metal-organic framework (MOF)/polymer mixed matrix membranes (MMMs) have received significant interest in the last decade. MOFs are incorporated into polymers to make MMMs that exhibit improved gas permeability and selectivity compared with pure polymer membranes. The fundamental challenge in this area is to choose the appropriate MOF/polymer combinations for a gas separation of interest. Even if a single polymer is considered, there are thousands of MOFs that could potentially be used as fillers in MMMs. As a result, there has been a large demand for computational studies that can accurately predict the gas separation performance of MOF/polymer MMMs prior to experiments. We have developed computational approaches to assess gas separation potentials of MOF/polymer MMMs and used them to identify the most promising MOF/polymer pairs. In this Personal Account, we aim to provide a critical overview of current computational methods for modeling MOF/polymer MMMs. We give our perspective on the background, successes, and failures that led to developments in this area and discuss the opportunities and challenges of using computational methods for MOF/polymer MMMs. PMID- 26842309 TI - Is There a Genetic Predisposition to Anterior Cruciate Ligament Tear? A Systematic Review. AB - BACKGROUND: Injuries to the anterior cruciate ligament (ACL) are among the most common knee ligament injuries and frequently warrant reconstruction. The etiopathogenesis of these injuries has focused mainly on mechanism of trauma, patient sex, and anatomic factors as predisposing causes. Several genetic factors that could predispose to an ACL tear have recently been reported. PURPOSE: This systematic review summarizes the current evidence for a genetic predisposition to ACL tears. The principal research question was to identify genetic factors, based on the available literature, that could predispose an individual to an ACL tear. STUDY DESIGN: Systematic review. METHODS: The PubMed, EMBASE, Cochrane, and HuGE databases were searched; the search was run from the period of inception until June 21, 2015. A secondary search was performed by screening the references of full-text articles obtained and by manually searching selected journals. Articles were screened with prespecified inclusion criteria. The quality of studies included in the review was assessed for risk of bias by 2 reviewers using the Newcastle-Ottawa Scale. RESULTS: A total of 994 records were identified by the search, out of which 17 studies (16 case-control studies and 1 cross-sectional study) were included in the final review. Two studies observed a familial predisposition to an ACL tear. Fourteen studies looked at specific gene polymorphisms in 20 genes, from which different polymorphisms in 10 genes were positively associated with an ACL tear. In addition to these polymorphisms, 8 haplotypes were associated with ACL tear. One study looked at gene expression analysis. CONCLUSION: Although specific gene polymorphisms and haplotypes have been identified, it is difficult to come to a conclusion on the basis of the existing literature. Several sources of bias have been identified in these studies, and the results cannot be extrapolated to the general population. More studies are needed in larger populations of different ethnicities. Gene-gene interactions and gene expression studies in the future may delineate the exact role of these gene polymorphisms in ACL tears. PMID- 26842310 TI - Immediate Effects of a Brace on Gait Biomechanics for Predominant Lateral Knee Osteoarthritis and Valgus Malalignment After Anterior Cruciate Ligament Reconstruction. AB - BACKGROUND: Lateral knee osteoarthritis is notably common after anterior cruciate ligament reconstruction (ACLR). While valgus bracing has been investigated as an intervention for medial knee osteoarthritis (OA), little is known about the effectiveness of varus bracing for lateral knee OA after ACLR. PURPOSE: To determine the immediate effects of a varus unloader knee brace on gait biomechanics in people with lateral knee OA and valgus malalignment after ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: Nineteen participants who had undergone primary ACLR 5 to 20 years previously and had symptomatic and radiographic lateral knee OA as well as valgus malalignment were included. Three dimensional gait analyses were conducted during walking under 3 test conditions: (1) no brace, (2) unadjusted brace (sagittal plane support with neutral frontal plane adjustment), and (3) adjusted brace (sagittal plane support with varus adjustment). Knee, pelvis, hip, and ankle kinematics and moments data were statistically analyzed using repeated-measures analysis of variance (alpha = 0.05). RESULTS: Compared with walking with no brace, the adjusted brace significantly increased peak knee flexion angle (mean difference [95% CI]: 3.2 degrees [1.3 degrees to 5.0 degrees ]) and adduction angle (1.7 degrees [0.8 degrees to 2.6 degrees ]) and reduced peak internal rotation angle (-3.0 degrees [-4.0 degrees to -2.0 degrees ]). Significant increases in peak knee flexion moment (0.14 N.m/kg [0.06 to 0.20 N.m/kg]), adduction moment (0.10 N.m/kg [0.07 to 0.14 N.m/kg]), and external rotation moment (0.01 N.m/kg [0.00 to 0.02 N.m/kg]) were observed with the adjusted brace. The adjusted brace also reduced peak hip adduction angle (-1.29 degrees [-2.12 to -0.47]) and increased peak hip adduction (0.17 N.m/kg [0.04 to 0.31 N.m/kg]) and external rotation moments (0.09 N.m/kg [0.03 to 0.14 N.m/kg]). There were no significant differences between the adjusted and unadjusted brace conditions, except for knee internal rotation angle, where the adjusted brace produced significantly greater reductions relative to the unadjusted brace (-1.46 degrees [-1.98 to -0.95]). CONCLUSION: Irrespective of frontal plane adjustment, the varus unloader brace produced immediate modulations in sagittal, frontal, and transverse plane joint angles and moments in younger individuals with lateral knee OA and valgus malalignment after ACLR. CLINICAL RELEVANCE: The varus unloader brace may have the potential to mitigate abnormal knee joint mechanics associated with the development and progression of lateral knee OA after ACLR. PMID- 26842311 TI - One-Year Outcomes of Total Meniscus Reconstruction Using a Novel Fiber-Reinforced Scaffold in an Ovine Model. AB - BACKGROUND: Meniscus injuries and resulting meniscectomies lead to joint deterioration, causing pain, discomfort, and instability. Tissue-engineered devices to replace the meniscus have not shown consistent success with regard to function, mechanical integrity, or protection of cartilage. PURPOSE: To evaluate a novel resorbable polymer fiber-reinforced meniscus reconstruction scaffold in an ovine model for 52 weeks and assess its integrity, tensile and compressive mechanics, cell phenotypes, matrix organization and content, and protection of the articular cartilage surfaces. STUDY DESIGN: Controlled laboratory study. METHODS: Eight skeletally mature ewes were implanted with the fiber-reinforced scaffold after total meniscectomy, and 2 additional animals had untreated total meniscectomies. Animals were sacrificed at 52 weeks, and the explants and articular surfaces were analyzed macroscopically. Explants were characterized by ultimate tensile testing, confined compression creep testing, and biochemical, histological, and immunohistochemical analyses. Cartilage damage was characterized using the Mankin score on histologic slides from both the femur and tibia. RESULTS: One sheep was removed from the study because of a torn extensor tendon; the remaining 7 explants remained fully intact and incorporated into the bone tunnels. All explants exhibited functional tensile loads, tensile stiffnesses, and compressive moduli. Fibrocartilagenous repair with both types 1 and 2 collagen were observed, with areas of matrix organization and biochemical content similar to native tissue. Narrowing in the body region was observed in 5 of 7 explants. Mankin scores showed less cartilage damage in the explant group (femoral condyle: 3.43 +/- 0.79, tibial plateau: 3.50 +/- 1.63) than in the meniscectomy group (femoral condyle: 8.50 +/- 3.54, tibial plateau: 6.75 +/- 2.47) and were comparable with Mankin scores at the previously reported 16- and 32-week time points. CONCLUSION: A resorbable fiber-reinforced meniscus scaffold supports formation of functional neomeniscus tissue, with the potential to prevent joint degeneration that typically occurs after total meniscectomy. Further studies with improvements to the initial mechanics of the scaffold and testing for longer time periods are warranted. CLINICAL RELEVANCE: Meniscectomy is an extremely common orthopaedic procedure, and few options currently exist for the treatment of significant loss of meniscus tissue. Successful development of a tissue-engineered meniscus scaffold could substantially reduce the incidence of postmeniscectomy joint degeneration and the subsequent procedures used for its treatment. PMID- 26842312 TI - Comparison of Anatomic Posterolateral Knee Reconstruction Using 2 Different Popliteofibular Ligament Techniques. AB - BACKGROUND: Anatomic posterolateral knee reconstruction is a surgical procedure that reconstructs the lateral collateral ligament (LCL), the popliteus tendon, and the popliteofibular ligament (PFL). Until recently, diverse techniques have been reported for this reconstruction; however, the gold standard is still a matter of debate. HYPOTHESIS: Clinical outcomes and stability with tibiofibular based PFL reconstruction would be better than those with femorofibular-based PFL reconstruction. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The records of 10 patients who underwent anatomic posterolateral knee reconstruction between January 2011 and December 2012 (LCL, popliteus tendon, tibiofibular-based PFL reconstruction [group A]) with a minimum follow-up of 24 months were retrospectively reviewed. Ten patients who underwent anatomic posterolateral knee reconstruction (LCL, popliteus tendon, femorofibular-based PFL reconstruction [group B]) using a split Achilles tendon allograft were recruited into a matched control group. All patients in both groups had an associate posterior cruciate ligament (PCL) injury, and 8 in each group underwent concomitant PCL reconstruction. Clinical outcomes were evaluated with International Knee Documentation Committee (IKDC) subjective, Lysholm, and Tegner activity scale scores. Knee stability was assessed with the dial test for the evaluation of external rotation as well as varus and posterior instability by stress radiography. RESULTS: The mean (+/-SD) follow-up period was 29.5 +/- 3.8 months in group A and 60.4 +/- 33.8 months in group B. There were no clinically significant between-group differences in IKDC subjective scores (group A: 83.8 +/ 5.4, group B: 82.7 +/- 6.5; P = .853), Lysholm scores (group A: 83.4 +/- 5.1, group B: 84.1 +/- 7.3; P = .853), or Tegner activity scale scores (group A: 4.8 +/- 1.4, group B: 4.2 +/- 0.9; P = .436) at the final follow-up. In addition, there was no difference in side-to-side measurements on varus stress radiography (group A: 0.9 +/- 0.7 mm, group B: 1.3 +/- 1.2 mm; P = .481) or posterior stress radiography (group A: 5.3 +/- 1.9 mm, group B: 5.4 +/- 2.2 mm; P = .971) at the final follow-up. Although the external rotation grade of the tibia was not significantly different between groups preoperatively (P = .709), it was smaller in group A at the final follow-up (P = .044). CONCLUSION: There were no significant differences in clinical outcomes or varus stability between the 2 techniques of PFL reconstruction in patients with posterolateral corner injuries who underwent anatomic posterolateral knee reconstruction. However, the external rotation grade of the tibia was smaller in the group that underwent tibiofibular based PFL reconstruction. PMID- 26842314 TI - Different strategies of osmoadaptation in the closely related marine myxobacteria Enhygromyxa salina SWB007 and Plesiocystis pacifica SIR-1. AB - Only a few myxobacteria are known to date which are classified as marine due to their salt-dependency. In this study, the salt tolerance mechanism of these bacteria was investigated. Therefore, a growth medium was designed, in which the mutated Escherichia coli strain BKA13 served as sole food source for the predatory, heterotrophic myxobacteria. This enabled measurement of the osmolytes without any background and revealed that the closely related strains Enhygromyxa salina SWB007 and Plesiocystis pacifica SIR-1 developed different strategies to handle salt stress. P. pacifica SIR-1, which was grown between 1-4 % NaCl, relies solely on the accumulation of amino acids, while E. salina SWB007, which was grown between 0.5-3 % NaCl, employs, beside betaine, hydroxyectoine as the major compatible solute. In accordance with this analysis, only in the latter strain a gene locus was identified which codes for genes corresponding to the biosynthesis of betaine, ectoine, and hydroxyectoine. PMID- 26842313 TI - Expression Profile of Long Noncoding RNAs in Peripheral Blood Mononuclear Cells from Multiple Sclerosis Patients. AB - AIMS: Long noncoding RNAs (lncRNAs) play a key role in regulating immunological functions. Their impact on the chronic inflammatory disease multiple sclerosis (MS), however, remains unknown. We investigated the expression of lncRNAs in peripheral blood mononuclear cells (PBMCs) of patients with MS and attempt to explain their possible role in the process of MS. METHODS: For this study, we recruited 26 patients with MS according to the revised McDonald criteria. Then, we randomly chose 6 patients for microarray analysis. Microarray assays identified outstanding differences in lncRNA expression, which were verified through real-time PCR. LncRNA functions were annotated for target genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and regulatory relationships between lncRNAs and target genes were analyzed using the "cis" and "trans" model. RESULTS: There were 2353 upregulated lncRNAs, 389 downregulated lncRNAs, 1037 upregulated mRNAs, and 279 downregulated mRNAs in patients with MS compared to healthy control subjects (fold change >2.0). Real time PCR results of six aberrant lncRNAs were consistent with the microarray data. The coexpression network comprised 864 lncRNAs and 628 mRNAs. Among differentially expressed lncRNAs, 10 lncRNAs were predicted to have 10 cis regulated target genes, and 33 lncRNAs might regulate their trans target genes. CONCLUSIONS: We identified a subset of dysregulated lncRNAs and mRNAs. The differentially expressed lncRNAs may be important in the process of MS. However, the specific molecular mechanisms and biological functions of these lncRNAs in the pathogenesis of MS need further study. PMID- 26842315 TI - Retraction of "Women's Preference for Attractive Makeup Tracks Changes in Their Salivary Testosterone". AB - At the request of the authors, the following article has been retracted by the Editor and publishers of Psychological Science:Fisher, C. I., Hahn, A. C., DeBruine, L. M., & Jones, B. C. (2015). Women's preference for attractive makeup tracks changes in their salivary testosterone. Psychological Science, 26, 1958 1964. doi:10.1177/0956797615609900. PMID- 26842316 TI - Low Childhood Socioeconomic Status Promotes Eating in the Absence of Energy Need. AB - Life-history theory predicts that exposure to conditions typical of low socioeconomic status (SES) during childhood will calibrate development in ways that promote survival in harsh and unpredictable ecologies. Guided by this insight, the current research tested the hypothesis that low childhood SES will predict eating in the absence of energy need. Across three studies, we measured (Study 1) or manipulated (Studies 2 and 3) participants' energy need and gave them the opportunity to eat provided snacks. Participants also reported their SES during childhood and their current SES. Results revealed that people who grew up in high-SES environments regulated their food intake on the basis of their immediate energy need; they ate more when their need was high than when their need was low. This relationship was not observed among people who grew up in low SES environments. These individuals consumed comparably high amounts of food when their current energy need was high and when it was low. Childhood SES may have a lasting impact on food regulation. PMID- 26842318 TI - Energy Storage Research in Switzerland - The SCCER Heat & Electricity Storage. PMID- 26842317 TI - To Live Among Like-Minded Others: Exploring the Links Between Person-City Personality Fit and Self-Esteem. AB - Does it matter if your personality fits in with the personalities of the people where you live? The present study explored the links between person-city personality fit and self-esteem. Using data from 543,934 residents of 860 U.S. cities, we examined the extent to which the fit between individuals' Big Five personality traits and the Big Five traits of the city where they live (i.e., the prevalent traits of the city's inhabitants) predicts individuals' self-esteem. To provide a benchmark for these effects, we also estimated the degree to which the fit between person and city religiosity predicts individuals' self-esteem. The results provided a nuanced picture of the effects of person-city personality fit on self-esteem: We found significant but small effects of fit on self-esteem only for openness, agreeableness, and conscientiousness, rather than effects for all Big Five traits. Similar results and effect sizes were observed for religiosity. We conclude with a discussion of the relevance and limitations of this study. PMID- 26842319 TI - Evaluation of Metal Phosphide Nanocrystals as Anode Materials for Na-ion Batteries. AB - Sodium-ion batteries (SIBs) are potential low-cost alternatives to lithium-ion batteries (LIBs) because of the much greater natural abundance of sodium salts. However, developing high-performance electrode materials for SIBs is a challenging task, especially due to the ~50% larger ionic radius of the Na(+) ion compared to Li(+), leading to vastly different electrochemical behavior. Metal phosphides such as FeP, CoP, NiP(2), and CuP(2) remain unexplored as electrode materials for SIBs, despite their high theoretical charge storage capacities of 900-1300 mAh g(-1). Here we report on the synthesis of metal phosphide nanocrystals (NCs) and discuss their electrochemical properties as anode materials for SIBs, as well as for LIBs. We also compare the electrochemical characteristics of phosphides with their corresponding sulfides, using the environmentally benign iron compounds, FeP and FeS(2), as a case study. We show that despite the appealing initial charge storage capacities of up to 1200 mAh g( 1), enabled by effective nanosizing of the active electrode materials, further work toward optimization of the electrode/electrolyte pair is needed to improve the electrochemical performance upon cycling. PMID- 26842320 TI - Electrode Engineering of Conversion-based Negative Electrodes for Na-ion Batteries. AB - Due to lower costs and higher abundance of sodium, Na-ion battery technology can offer a good alternative to Li-ion batteries. Much research is focusing on developing new cathode and anode materials but the importance of the electrode engineering on the electrochemical performance is often neglected. The electrode composition is especially crucial for conversion reaction-based materials where the composite electrode (active material, conducting additive and binder) has to buffer the huge volume change occurring upon cycling. This work highlights the differences observed on Sn-CMC electrode performance by using different Sn particle sizes (micro- and nanoparticles) and evaluating the role of the conductive additive in the electrode. Carbon fibers (VGCF) demonstrate a good ability to surround micrometer particles but not especially nanometer particles leading to an improvement in the performance of microparticles but not of nanoparticles. For a high loading electrode suitable for full cell applications (>3.5 mg/cm(2) of active material), nanometer particles show limited performance for long-term cycling. The combination of VGCF with micrometer particles seems to be the most promising composition to obtain good performances for conversion reaction based-materials. PMID- 26842321 TI - Nanomaterials Meet Li-ion Batteries. AB - Li-ion batteries are used in many applications in everyday life: cell phones, laser pointers, laptops, cordless drillers or saws, bikes and even cars. Yet, there is room for improvement in order to make the batteries smaller and last longer. The Fromm group contributes to this research focusing mainly on nanoscale lithium ion cathode materials. This contribution gives an overview over our current activities in the field of batteries. After an introduction on the nano materials of LiCoO(2) and LiMnPO(4), the studies of our cathode composition and preparation will be presented. PMID- 26842322 TI - Stress-induced Ageing of Lithium-Ion Batteries. AB - Lithium-ion batteries are well established for use in portable consumer products and are increasingly used in high power electro-mobility and photovoltaic storage applications. In hybrid and plug-in electric vehicles degradation and useful lifetime at standard operation conditions are critical parameters in addition to performance and safety. Here stress-induced ageing of commercially available high power battery cells of the type A123 AHR32113M1 Ultra-B, consisting of a LiFePO(4) cathode and a graphite anode have been investigated. A usually accepted capacity loss for electric vehicles of 20% was reached after 8560 stress profiles corresponding to a driving distance of almost 200'000 km. Cycling with a stress profile applying constant power corresponding to the average power and energy of a full stress profile and starting at 60% state of charge showed a much faster capacity loss. Electric impedance measurements show the dependence of the capacity loss and constant phase element at low frequency, indicating Li-ion diffusion blocking in the cathode. Microscopic analysis of anode, separator, and cathode, shows defect formation in bulk material and at interfaces. PMID- 26842323 TI - Storing Renewable Energy in the Hydrogen Cycle. AB - An energy economy based on renewable energy requires massive energy storage, approx. half of the annual energy consumption. Therefore, the production of a synthetic energy carrier, e.g. hydrogen, is necessary. The hydrogen cycle, i.e. production of hydrogen from water by renewable energy, storage and use of hydrogen in fuel cells, combustion engines or turbines is a closed cycle. Electrolysis splits water into hydrogen and oxygen and represents a mature technology in the power range up to 100 kW. However, the major technological challenge is to build electrolyzers in the power range of several MW producing high purity hydrogen with a high efficiency. After the production of hydrogen, large scale and safe hydrogen storage is required. Hydrogen is stored either as a molecule or as an atom in the case of hydrides. The maximum volumetric hydrogen density of a molecular hydrogen storage is limited to the density of liquid hydrogen. In a complex hydride the hydrogen density is limited to 20 mass% and 150 kg/m(3) which corresponds to twice the density of liquid hydrogen. Current research focuses on the investigation of new storage materials based on combinations of complex hydrides with amides and the understanding of the hydrogen sorption mechanism in order to better control the reaction for the hydrogen storage applications. PMID- 26842324 TI - Hydrogen Storage in the Carbon Dioxide - Formic Acid Cycle. AB - This year Mankind will release about 39 Gt carbon dioxide into the earth's atmosphere, where it acts as a greenhouse gas. The chemical transformation of carbon dioxide into useful products becomes increasingly important, as the CO(2) concentration in the atmosphere has reached 400 ppm. One approach to contribute to the decrease of this hazardous emission is to recycle CO(2), for example reducing it to formic acid. The hydrogenation of CO(2) can be achieved with a series of catalysts under basic and acidic conditions, in wide variety of solvents. To realize a hydrogen-based charge-discharge device ('hydrogen battery'), one also needs efficient catalysts for the reverse reaction, the dehydrogenation of formic acid. Despite of the fact that the overwhelming majority of these reactions are carried out using precious metals-based catalysts (mainly Ru), we review here developments for catalytic hydrogen evolution from formic acid with iron-based complexes. PMID- 26842325 TI - Redox Flow Batteries, Hydrogen and Distributed Storage. AB - Social, economic, and political pressures are causing a shift in the global energy mix, with a preference toward renewable energy sources. In order to realize widespread implementation of these resources, large-scale storage of renewable energy is needed. Among the proposed energy storage technologies, redox flow batteries offer many unique advantages. The primary limitation of these systems, however, is their limited energy density which necessitates very large installations. In order to enhance the energy storage capacity of these systems, we have developed a unique dual-circuit architecture which enables two levels of energy storage; first in the conventional electrolyte, and then through the formation of hydrogen. Moreover, we have begun a pilot-scale demonstration project to investigate the scalability and technical readiness of this approach. This combination of conventional energy storage and hydrogen production is well aligned with the current trajectory of modern energy and mobility infrastructure. The combination of these two means of energy storage enables the possibility of an energy economy dominated by renewable resources. PMID- 26842326 TI - CO2 Hydrogenation: Supported Nanoparticles vs. Immobilized Catalysts. AB - The conversion of CO(2) to more valuable chemicals has been the focus of intense research over the past decades, and this field has become particularly important in view of the continuous increase of CO(2) levels in our atmosphere and the need to find alternative ways to store excess energy into fuels. In this review we will discuss different strategies for CO(2) conversion with heterogeneous and homogeneous catalysts. In addition, we will introduce some promising research concerning the immobilization of homogeneous catalysts on heterogeneous supports, as a hybrid of hetero- and homogeneous catalysts. PMID- 26842327 TI - Soft Approaches to CO2 Activation. AB - The utilization of CO(2) as a C1 synthon is becoming increasingly important as a feedstock derived from carbon capture and storage technologies. Herein, we describe some of our recent research on carbon dioxide valorization, notably, using organocatalysts to convert CO(2) into carboxylic acid, ester, formyl and methyl groups on various organic molecules. We describe these studies within the broader context of CO(2) capture and valorization and suggest approaches for future research. PMID- 26842328 TI - Electrochemical CO2 Reduction - A Critical View on Fundamentals, Materials and Applications. AB - The electrochemical reduction of CO(2) has been extensively studied over the past decades. Nevertheless, this topic has been tackled so far only by using a very fundamental approach and mostly by trying to improve kinetics and selectivities toward specific products in half-cell configurations and liquid-based electrolytes. The main drawback of this approach is that, due to the low solubility of CO(2) in water, the maximum CO(2) reduction current which could be drawn falls in the range of 0.01-0.02 A cm(-2). This is at least an order of magnitude lower current density than the requirement to make CO(2)-electrolysis a technically and economically feasible option for transformation of CO(2) into chemical feedstock or fuel thereby closing the CO(2) cycle. This work attempts to give a short overview on the status of electrochemical CO(2) reduction with respect to challenges at the electrolysis cell as well as at the catalyst level. We will critically discuss possible pathways to increase both operating current density and conversion efficiency in order to close the gap with established energy conversion technologies. PMID- 26842329 TI - Storage of Heat, Cold and Electricity. AB - A promising energy storage system is presented based on the combination of a heat pump, a heat engine, a hot and a cold storage. It can be operated as a pure bulk electricity storage (alternative to Pumped Heat Electrical Storage (PHES)/Compressed Air Energy Storage (CAES)) or as combined storage of heat, cold and electricity. Both variations have been evaluated using a steady state, thermodynamic model and two promising concepts are proposed: A transcritical CO(2) cycle for the pure electricity storage and a subcritical NH(3) cycle for combined storage of electricity, heat and cold. Parametric studies are used to evaluate the influence of different parameters on the roundtrip efficiency of the storage system. PMID- 26842330 TI - Phase Change Material Systems for High Temperature Heat Storage. AB - Efficient, cost effective, and stable high-temperature heat storage material systems are important in applications such as high-temperature industrial processes (metal processing, cement and glass manufacturing, etc.), or electricity storage using advanced adiabatic compressed air energy storage. Incorporating phase change media into heat storage systems provides an advantage of storing and releasing heat at nearly constant temperature, allowing steady and optimized operation of the downstream processes. The choice of, and compatibility of materials and encapsulation for the phase change section is crucial, as these must guarantee good and stable performance and long lifetime at low cost. Detailed knowledge of the material properties and stability, and the coupled heat transfer, phase change, and fluid flow are required to allow for performance and lifetime predictions. We present coupled experimental-numerical techniques allowing prediction of the long-term performance of a phase change material-based high-temperature heat storage system. The experimental investigations focus on determination of material properties (melting temperature, heat of fusion, etc.) and phase change material and encapsulation interaction (stability, interface reactions, etc.). The computational investigations focus on an understanding of the multi-mode heat transfer, fluid flow, and phase change processes in order to design the material system for enhanced performance. The importance of both the experimental and numerical approaches is highlighted and we give an example of how both approaches can be complementarily used for the investigation of long term performance. PMID- 26842331 TI - Seasonal Solar Thermal Absorption Energy Storage Development. AB - This article describes a thermochemical seasonal storage with emphasis on the development of a reaction zone for an absorption/desorption unit. The heat and mass exchanges are modelled and the design of a suitable reaction zone is explained. A tube bundle concept is retained for the heat and mass exchangers and the units are manufactured and commissioned. Furthermore, experimental results of both absorption and desorption processes are presented and the exchanged power is compared to the results of the simulations. PMID- 26842332 TI - Challenges towards Economic Fuel Generation from Renewable Electricity: The Need for Efficient Electro-Catalysis. AB - Utilizing renewable sources of energy is very attractive to provide the growing population on earth in the future but demands the development of efficient storage to mitigate their intermittent nature. Chemical storage, with energy stored in the bonds of chemical compounds such as hydrogen or carbon-containing molecules, is promising as these energy vectors can be reserved and transported easily. In this review, we aim to present the advantages and drawbacks of the main water electrolysis technologies available today: alkaline and PEM electrolysis. The choice of electrode materials for utilization in very basic and very acid conditions is discussed, with specific focus on anodes for the oxygen evolution reaction, considered as the most demanding and energy consuming reaction in an electrolyzer. State-of-the-art performance of materials academically developed for two alternative technologies: electrolysis in neutral or seawater, and the direct electrochemical conversion from solar to hydrogen are also introduced. PMID- 26842333 TI - Experimental and Numerical Investigation of Combined Sensible/Latent Thermal Energy Storage for High-Temperature Applications. AB - Combined sensible/latent heat storage allows the heat-transfer fluid outflow temperature during discharging to be stabilized. A lab-scale combined storage consisting of a packed bed of rocks and steel-encapsulated AlSi(12) was investigated experimentally and numerically. Due to the small tank-to-particle diameter ratio of the lab-scale storage, void-fraction variations were not negligible, leading to channeling effects that cannot be resolved in 1D heat transfer models. The void-fraction variations and channeling effects can be resolved in 2D models of the flow and heat transfer in the storage. The resulting so-called bypass fraction extracted from the 2D model was used in the 1D model and led to good agreement with experimental measurements. PMID- 26842337 TI - Effect of Experimental Parameters on Water Splitting Using a Hematite Photoanode. AB - Many studies designate hematite as a promising material for direct water splitting into hydrogen and oxygen. For a real outdoor application, it is important to consider hourly and seasonal conditions like temperature and sunlight intensity. The performance of an undoped hematite thin-film photoanode was tested in a photoelectrochemical cell under varying conditions of temperature and light intensity. Both parameters show a positive effect on performance under outdoor conditions. PMID- 26842338 TI - Platform for a Technological Leap in Antibiotics. AB - NTN Swiss BiotechTM brings together the Swiss Biotech Association SBA, which is involved in regulatory, financial and legal issues, and biotechnet Switzerland, which is active in translational R&D, to provide a technology base for joint projects. Biotechnet aims to push promising domains by creating topic-oriented platforms that enable academia and industry to work together to produce R&D results of major importance to society and the economy. The first activity initiated by biotechnet is the Antibiotics Platform that has now been launched. PMID- 26842339 TI - Chemical Landmark 2015 - Designation of the Former Institute of Chemistry of the University of Fribourg. PMID- 26842340 TI - Backward spoof surface wave in plasmonic metamaterial of ultrathin metallic structure. AB - Backward wave with anti-parallel phase and group velocities is one of the basic properties associated with negative refraction and sub-diffraction image that have attracted considerable interest in the context of photonic metamaterials. It has been predicted theoretically that some plasmonic structures can also support backward wave propagation of surface plasmon polaritons (SPPs), however direct experimental demonstration has not been reported, to the best of our knowledge. In this paper, a specially designed plasmonic metamaterial of corrugated metallic strip has been proposed that can support backward spoof SPP wave propagation. The dispersion analysis, the full electromagnetic field simulation and the transmission measurement of the plasmonic metamaterial waveguide have clearly validated the backward wave propagation with dispersion relation possessing negative slope and opposite directions of group and phase velocities. As a further verification and application, a contra-directional coupler is designed and tested that can route the microwave signal to opposite terminals at different operating frequencies, indicating new application opportunities of plasmonic metamaterial in integrated functional devices and circuits for microwave and terahertz radiation. PMID- 26842341 TI - Predictive factors for ocular complications caused by anticancer drug S-1. AB - PURPOSE: To identify predictive factors for ocular complications caused by the anticancer drug S-1. METHODS: A questionnaire was administered to 39 patients who underwent S-1 chemotherapy at Kobe City Medical Center General Hospital, with the aim to determine whether these patients were aware of the ocular complications caused by S-1. Cognition rate was determined. The 26 patients who requested opthalmological examination for further evaluation studied further and classified into two groups-those who had developed corneal epithelial complications, conjunctival injection or chemosis, or lacrimal duct blockages (referred to as the positive group) and those without these findings (referred to as the negative group). Predictive factors, such as age, sex, total administration days, total dose, presence or absence of anticancer drug pretreatment, and single-drug or combination-drug therapy, were investigated and compared between groups. RESULTS: Of the 39 patients who completed the questionnaire, ten were aware of the potential for ocular complications due to S-1 chemotherapy (cognition rate 25.6 %). Of the 26 patients who had requested opthalmological examination and entered into the study, 13 (26 eyes) were classified into the positive group, with corneal complications observed in 15 eyes (57.7 %), conjunctivitis in 26 eyes (100 %), and lacrimal duct blockage in 14 eyes (53.8 %). Cognition rate in the 13 patients in the positive group and the 13 patients in the negative group was 38.5 % (5 patients) and 7.7 % (1 patient), respectively. Patient age was significantly different between the two groups, with the patients in the positive group being significantly older than those in the negative group (mean age +/- standard deviation: 71.6 +/- 6.8 vs. 63.5 +/- 7.3 years, respectively; P = 0.0077, Student's t test). No other significant predictive factors were detected. CONCLUSION: Older patients were at greater risk of S-1-related ocular complications, but these complications were not associated with total administration days or total dose. PMID- 26842344 TI - Transient seizure-related MRI abnormalities in a child with primary Epstein-Barr virus infection. AB - We describe the case of a 6-year-old girl with typical infectious mononucleosis syndrome complicated by clustered right hemiconvulsions and disturbed consciousness. Diffusion-weighted magnetic resonance imaging on admission demonstrated reduced diffusion in the left temporo-posterior cortex and pulvinar of the ipsilateral thalamus. Her neurological symptoms resolved completely by the next day, with complete disappearance of abnormal signal intensities on magnetic resonance imaging (MRI). Elevated cerebrospinal fluid interleukin (IL)-6 with normal IL-10 might indicate a neuroprotective role of IL-6 rather than injury. We concluded that the MRI abnormalities could have been due to the seizure activity itself rather than Epstein-Barr virus-associated encephalitis. The recognition of transient seizure-related MRI abnormalities may help in the diagnostic approach to MRI changes in suspected encephalopathy. PMID- 26842342 TI - A monoclonal antibody against KCNK9 K(+) channel extracellular domain inhibits tumour growth and metastasis. AB - Two-pore domain potassium (K2P) channels act to maintain cell resting membrane potential--a prerequisite for many biological processes. KCNK9, a member of K2P family, is implicated in cancer, owing to its overexpression in human tumours and its ability to promote neoplastic cell survival and growth. However, KCNK9's underlying contributions to malignancy remain elusive due to the absence of specific modulators. Here we describe the development of monoclonal antibodies against the KCNK9 extracellular domain and their functional effects. We show that one antibody (Y4) with the highest affinity binding induces channel internalization. The addition of Y4 to KCNK9-expressing carcinoma cells reduces cell viability and increases cell death. Systemic administration of Y4 effectively inhibits growth of human lung cancer xenografts and murine breast cancer metastasis in mice. Evidence for Y4-mediated carcinoma cell autonomous and immune-dependent cytotoxicity is presented. Our study reveals that antibody-based KCNK9 targeting is a promising therapeutic strategy in KCNK9-expressing malignancies. PMID- 26842343 TI - An Overview of Occupational Risks From Climate Change. AB - Changes in atmosphere and temperature are affecting multiple environmental indicators from extreme heat events to global air quality. Workers will be uniquely affected by climate change, and the occupational impacts of major shifts in atmospheric and weather conditions need greater attention. Climate change related exposures most likely to differentially affect workers in the USA and globally include heat, ozone, polycyclic aromatic hydrocarbons, other chemicals, pathogenic microorganisms, vector-borne diseases, violence, and wildfires. Epidemiologic evidence documents a U-, J-, or V-shaped relationship between temperature and mortality. Whereas heat-related morbidity and mortality risks are most evident in agriculture, many other outdoor occupational sectors are also at risk, including construction, transportation, landscaping, firefighting, and other emergency response operations. The toxicity of chemicals change under hyperthermic conditions, particularly for pesticides and ozone. Combined with climate-related changes in chemical transport and distribution, these interactions represent unique health risks specifically to workers. Links between heat and interpersonal conflict including violence require attention because they pose threats to the safety of emergency medicine, peacekeeping and humanitarian relief, and public safety professionals. Recommendations for anticipating how US workers will be most susceptible to climate change include formal monitoring systems for agricultural workers; modeling scenarios focusing on occupational impacts of extreme climate events including floods, wildfires, and chemical spills; and national research agenda setting focusing on control and mitigation of occupational susceptibility to climate change. PMID- 26842345 TI - Giant Cell Tumor of Bone With Pseudosarcomatous Changes Leading to Premature Denosumab Therapy Interruption: A Case Report With Review of the Literature. AB - Denosumab has shown promising results in the management of giant cell tumor of bone, a primary bone tumor with locally aggressive behaviour. We report a case of premature denosumab interruption due to radiological and clinical tumor expansion of a giant cell tumor of the distal ulna. Although denosumab is known to induce tumor regression, with progressive ossification and loss of the characteristic morphology of giant cell tumor of bone, the ulnar tumor specimen showed a moderately to highly cellular proliferation of short spindle-shaped cells, and no osteoclast-like giant cells. There were no abnormal mitotic figures. We considered the surgical specimen as a giant cell tumor of bone with partial regression after prematurely interrupted denosumab treatment. This case illustrates the diagnostic issues of an initially unfavourable evolution raising concern for malignancy, and the difficulties in histological assessment of a partially treated giant cell tumor of bone, that may mimic osteosarcoma. PMID- 26842346 TI - Aberrant Expression of Napsin A in Breast Carcinoma With Apocrine Features. AB - An incidental finding of napsin A-positive breast carcinoma with apocrine features during workup for metastatic cancer in an axillary lymph node led to our investigation of the incidence of napsin A expression in breast carcinomas, focusing on those with apocrine features. We included 97 cases of breast carcinomas and performed immunohistochemistry with napsin A, GATA-3, thyroid transcription factor-1, and GCDFP-15. There was a statistically significant difference between apocrine and nonapocrine cases with respect to polyclonal napsin A H-scores (P < .00152), monoclonal napsin A H-scores (P < .00631), GATA-3 H-scores (P < .00029), and GCDFP-15 H-scores (P < .00251). Of the 49 cases of apocrine carcinoma, monoclonal napsin A antibody was positive in 66.7% of cases, including in 7 (14.6%) that showed 3+ staining. The majority of nonapocrine cases were negative (62.5%) or weakly (1+) positive (29.2%), with none exhibiting 3+ strength. It is important for pathologists to be aware that breast carcinomas with apocrine features can express napsin A. PMID- 26842347 TI - Targeted Screening With Combined Age- and Morphology-Based Criteria Enriches Detection of Lynch Syndrome in Endometrial Cancer. AB - Endometrial cancer is associated with Lynch syndrome in 2% to 6% of cases. Adequate screening may prevent of a second cancer and incident cancers in family members via risk-reducing strategies. The goal of the study was to evaluate the detection rate of Lynch syndrome via a targeted screening approach. In 2009, we incorporated targeted Lynch syndrome screening via immunohistochemistry for MLH1, PMS2, MSH2, and MSH6, followed by MLH1 promoter hypermethylation, in select cases of endometrial carcinoma. Criteria for patient selection included (1) all patients <50 years; (2) patients of any age with tumors showing features of microsatellite instability (lower uterine segment-centered tumors, hard to classify carcinomas, increased peritumoral or tumor infiltrating lymphocytes and cases with synchronous ovarian carcinomas); (3) clinician's request based on family or personal history; and (4) ad hoc retrospective testing based on the established criteria on patients discovered on follow-up visits. By using a targeted screening approach in a 4.5-year period, approximately 2.1% of endometrial cancers (7 of 328) were potentially associated with Lynch syndrome. Therefore, targeted screening with combined age and morphology based criteria enriches detection of Lynch syndrome in endometrial cancer. However, the detection rate is lower than the rates from published series that offer universal screening. PMID- 26842348 TI - Tick Bite Reaction: Caught in the Act. PMID- 26842349 TI - WHEN TWO IS BETTER THAN ONE. AB - Looking for the perfect sequencing instrument for your next experiment? As Jeffrey Perkel finds out, you might just need more than one. PMID- 26842350 TI - Genetically encoded far-red fluorescent sensors for caspase-3 activity. AB - Caspase-3 is a key effector caspase that is activated in both extrinsic and intrinsic pathways of apoptosis. Available fluorescent sensors for caspase-3 activity operate in relatively short wavelength regions and are nonoptimal for multiparameter microscopy and whole-body imaging. In the present work, we developed new genetically encoded sensors for caspase-3 activity possessing the most red-shifted spectra to date. These consist of Forster resonance energy transfer (FRET) pairs in which a far-red fluorescent protein (mKate2 or eqFP650) is connected to the infrared fluorescent protein iRFP through a linker containing the DEVD caspase-3 cleavage site. During staurosporine-induced apoptosis of mammalian cells (HeLa and CT26), both mKate2-DEVD-iRFP and eqFP650-DEVD-iRFP sensors showed a robust response (1.6-fold increase of the donor fluorescence intensity). However, eqFP650-DEVD-iRFP displayed aggregation in some cells. For stably transfected CT26 mKate2-DEVD-iRFP cells, fluorescence lifetime imaging (FLIM) enabled us to detect caspase-3 activation due to the increase of mKate2 donor fluorescence lifetime from 1.45 to 2.05 ns. We took advantage of the strongly red-shifted spectrum of mKate2-DEVD-iRFP to perform simultaneous imaging of EGFP-Bax translocation during apoptosis. We conclude that mKate2-DEVD-iRFP is well-suited for multiparameter imaging and also potentially beneficial for in vivo imaging in animal tissues. PMID- 26842351 TI - Selectable one-step PCR-mediated integration of a degron for rapid depletion of endogenous human proteins. AB - Manipulation of protein stability with ligand-regulated degron fusions is a powerful method for investigating gene function. We developed a selectable cassette for easy C-terminal tagging of endogenous human proteins with the E. coli dihydrofolate reductase (eDHFR) degron using CRISPR/Cas9 genome editing. This cassette permits high-efficiency recovery of correct integration events using an in-frame self-cleaving 2A peptide and the puromycin resistance gene. PCR amplified donor eDHFR cassette fragments with 100 bases of homology on each end are integrated by homology-directed repair (HDR) of guide RNA (gRNA)-targeted double-stranded DNA breaks at the 3' ends of open reading frames (ORFs). As proof of principle, we generated cell lines in which three endogenous proteins were tagged with the eDHFR degron. When the antibiotic trimethoprim is removed from the media, each of the eDHFR-tagged proteins was depleted by >90% within 2-4 h, and this depletion was reversed by re-addition of trimethoprim. Since puromycin selection permits recovery of in-frame degron fusions with high efficiency using only 100-bp long regions of homology, this method should be applicable on a genome-wide scale for generating libraries of conditional mutant cell lines. PMID- 26842352 TI - Efficient large-scale preparation and purification of short single-stranded RNA oligonucleotides. AB - Sequence-specific RNA recognition by RNA-binding proteins plays a crucial role in the post-translational regulation of gene expression. Biophysical and biochemical studies help to unravel the principles of sequence-specific RNA recognition, but the methods used require large amounts of single-stranded RNA (ssRNA). Here we present a fast and robust method for large-scale preparation and purification of short ssRNA oligonucleotides for biochemical, biophysical, and structural studies. We designed an efficiently folding, self-cleaving hammerhead (HH) ribozyme to prepare ssRNA oligonucleotides. Hammerhead ribozyme RNAs self-cleave with over 95% efficiency during in vitro transcription as a function of magnesium concentration to produce high yields of the desired ssRNA products. The resulting ssRNAs can be purified from crude transcription reactions by denaturing anion exchange chromatography and then desalted by weak anion-exchange chromatography using volatile ammonium bicarbonate buffer solutions. The ssRNA oligonucleotides produced this way are homogenous, as judged by mass spectrometry (MS), and are suitable for biochemical and biophysical studies. Moreover, for high-resolution NMR structure determination of RNA-protein complexes, our protocol enables efficient preparation of ssRNA oligonucleotides with various isotope-labeling schemes which are not commercially available. PMID- 26842353 TI - IDLN-MSP: Idiolocal normalization of real-time methylation-specific PCR for genetic imbalanced DNA specimens. AB - Sensitive, accurate, and reliable measurements of tumor cell-specific DNA methylation changes are of fundamental importance in cancer diagnosis, prognosis, and monitoring. Real-time methylation-specific PCR (MSP) using intercalating dyes is an established method of choice for this purpose. Here we present a simple but crucial adaptation of this widely applied method that overcomes a major obstacle: genetic abnormalities in the DNA samples, such as aneuploidy or copy number variations, that could result in inaccurate results due to improper normalization if the copy numbers of the target and reference sequences are not the same. In our idiolocal normalization (IDLN) method, the locus for the normalizing, methylation-independent reference amplification is chosen close to the locus of the methylation-dependent target amplification. This ensures that the copy numbers of both the target and reference sequences will be identical in most cases if they are close enough to each other, resulting in accurate normalization and reliable comparative measurements of DNA methylation in clinical samples when using real-time MSP. PMID- 26842354 TI - A practical method for barcoding and size-trimming PCR templates for amplicon sequencing. AB - Sample barcoding facilitates the analysis of tens or even hundreds of samples in a single next-generation sequencing (NGS) run, but more efficient methods are needed for high-throughput barcoding and size-trimming of long PCR products. Here we present a two-step PCR approach for barcoding followed by pool shearing, adapter ligation, and 5' end selection for trimming sets of DNA templates of any size. Our new trimming method offers clear benefits for phylogenetic studies, since targeting exactly the same region maximizes the alignment and enables the use of operational taxonomic unit (OTU)-based algorithms. PMID- 26842355 TI - ReX: A suite of computational tools for the design, visualization, and analysis of chimeric protein libraries. AB - Directed evolution has greatly facilitated protein engineering and provided new insights into protein structure-function relationships. DNA shuffling using restriction enzymes is a particularly simple and cost-effective means of recombinatorial evolution that is well within the capability of most molecular biologists, but tools for the design and analysis of such experiments are limited. Here we introduce a suite of freely available online tools to make the construction and analysis of chimeric libraries readily accessible to the novice. REcut (http://qpmf.rx.umaryland.edu/REcut.html) facilitates the choice of DNA fragmentation strategy, while Xover (http://qpmf.rx.umaryland.edu/Xover.html) analyzes chimeric mutants to reveal recombination patterns and extract quantitative data. PMID- 26842356 TI - Direct current electrical stimulation chamber for treating cells in vitro. AB - Electrical stimulation has been shown to promote healing and regeneration in skin, bone, muscle, and nerve tissues in clinical studies. Recently, studies applying electrical stimulation to influence cell behavior associated with proliferation, differentiation, and migration have provided a better understanding of the underlying mechanisms of electrical stimulation-based clinical treatments and improved tissue-engineered products through electro bioreactor technologies. Here, we present a novel device for delivering direct current (DC) electrical stimulation (ES) to cultivated cells in vitro. Our simplified electro-bioreactor is customized for applying DC electrical current simultaneously in six individual tissue culture wells. The design overcomes previous experimental replicate limitations, thus reducing experimental time and cost. PMID- 26842357 TI - Assessment of a course of realistic surgical training during medical education as a tool for pre-residential surgical training. AB - BACKGROUND: In recent years the focus on practical skills in the German curriculum of medical school has increased greatly. In this study we evaluate the value of a practical surgery course for medical students as a tool for surgical education, as a way of enhancing interest in surgical fields, and as a method of influencing medical students to subsequently choose a surgical career. METHODS: The "Feel like a surgeon"-course is an optional practical surgery course in which topographical anatomy and realistic surgical training using fresh human cadavers are combined for medical students of the RWTH Aachen University. Between 2010 and 2015 every student completed a survey before starting and after completing our course, and in 2015 a follow-up was performed. Using a standardized questionnaire, course quality, learning success and impact on post-instructional career and choice of profession was evaluated. RESULTS: In total, 82 students attended our course between 2010 and 2015 and took part in the evaluation. Evaluation of the course was positive overall, with an average grade of 1.4 degrees +/- degrees 0.50. Significant improvement of basic, as well as more complex surgical skills and theoretical knowledge was noted. Furthermore, self confidence for patient related assignments improved as well. In the follow-up evaluation, a high level of recommendation for surgical residents was seen, as was a high influence of the course on our students' career choice, although no significant change in career plans before and after taking the course was noted. CONCLUSIONS: Our results indicate that a practical surgical course can be a valuable tool to prepare students for a surgical residency and to improve their practical skills generally. PMID- 26842358 TI - Reconsideration of Intrinsic Band Alignments within Anatase and Rutile TiO2. PMID- 26842359 TI - Quantum Dots Continue to Shine Brightly. PMID- 26842361 TI - Erratum to: It could be a 'Golden Goose': a qualitative study of views in primary care on an emergency admission risk prediction tool prior to implementation. PMID- 26842360 TI - Vijana Vijiweni II: a cluster-randomized trial to evaluate the efficacy of a microfinance and peer health leadership intervention for HIV and intimate partner violence prevention among social networks of young men in Dar es Salaam. AB - BACKGROUND: Intimate partner violence (IPV) and sexually transmitted infections (STIs), including HIV, remain important public health problems with devastating health effects for men and women in sub-Saharan Africa. There have been calls to engage men in prevention efforts, however, we lack effective approaches to reach and engage them. Social network approaches have demonstrated effective and sustained outcomes on changing risk behaviors in the U.S. Our team has identified and engaged naturally occurring social networks comprised mostly of young men in Dar es Salaam in an intervention designed to jointly reduce STI incidence and the perpetration of IPV. These stable networks are locally referred to as "camps." In a pilot study we demonstrated the feasibility and acceptability of a combined microfinance and peer health leadership intervention within these camp-based peer networks. METHODS DESIGN: We are implementing a cluster-randomized trial to evaluate the efficacy of an intervention combining microfinance with health leadership training in 60 camps in Dar es Salaam, Tanzania. Half of the camps have been randomized to the intervention arm, and half to a control arm. The camps in the intervention arm will receive a combined microfinance and health leadership intervention for a period of two years. The camps in the control arm will receive a delayed intervention. We have enrolled 1,258 men across the 60 study camps. Behavioral surveys will be conducted at baseline, 12-months post intervention launch and 30-month post intervention launch and biological samples will be drawn to test for Neisseria gonorrhea (NG), Chlamydia trachomatis (CT), and Trichomonas vaginalis (TV) at baseline and 30-months. The primary endpoints for assessing intervention impact are IPV perpetration and STI incidence. DISCUSSION: This is the first cluster-randomized trial targeting social networks of men in sub-Saharan Africa that jointly addresses HIV and IPV perpetration and has both biological and behavioral endpoints. Effective approaches to engage men in HIV and IPV prevention are needed in low resource, high prevalence settings like Tanzania. If we determine that this approach is effective, we will examine how to adapt and scale up this approach to other urban, sub-Saharan African settings. TRIAL REGISTRATION: Clinical Trials.gov: NCT01865383 . Registration date: May 24, 2013. PMID- 26842362 TI - Spatio-temporal patterns and movement analysis of pigs from smallholder farms and implications for African swine fever spread, Limpopo province, South Africa. AB - Infectious and zoonotic disease outbreaks have been linked to increasing volumes of legal and illegal trade. Spatio-temporal and trade network analyses have been used to evaluate the risks associated with these challenges elsewhere, but few details are available for the pig sector in South Africa. Regarding pig diseases, Limpopo province is important as the greater part of the province falls within the African swine fever control area. Emerging small-scale pig farmers in Limpopo perceived pig production as an important means of improving their livelihood and an alternative investment. They engage in trading and marketing their products with a potential risk to animal health, because the preferred markets often facilitate potential longdistance spread and disease dispersal over broad geographic areas. In this study, we explored the interconnectedness of smallholder pig farmers in Limpopo, determined the weaknesses and critical control points, and projected interventions that policy makers can implement to reduce the risks to pig health. The geo-coordinates of surveyed farms were used to draw maps, links and networks. Predictive risks to pigs were determined through the analyses of trade networks, and the relationship to previous outbreaks of African swine fever was postulated. Auction points were identified as high-risk areas for the spread of animal diseases. Veterinary authorities should prioritise focused surveillance and diagnostic efforts in Limpopo. Early disease detection and prompt eradication should be targeted and messages promoting enhanced biosecurity to smallholder farmers are advocated. The system may also benefit from the restructuring of marketing and auction networks. Since geographic factors and networks can rapidly facilitate pig disease dispersal over large areas, a multi-disciplinary approach to understanding the complexities that exist around the animal disease epidemiology becomes mandatory. PMID- 26842363 TI - Time-series analysis of ruminant foetal wastage at a slaughterhouse in North Central Nigeria between 2001 and 2012. AB - In developing countries, foetal wastage from slaughtered ruminants and the associated economic losses appear to be substantial. However, only a limited number of studies have comprehensively evaluated these trends. In the current study, secondary (retrospective) and primary data were collected and evaluated to estimate the prevalence of foetal wastage from cattle, sheep and goats slaughtered at an abattoir in Minna, Nigeria, over a 12-year period (January 2001 December 2012). Time-series modelling revealed substantial differences in the rate of foetal wastage amongst the slaughtered species, with more lambs having been wasted than calves or kids. Seasonal effects seem to influence rates of foetal wastage and certain months in the year appear to be associated with higher odds of foetal wastage. Improved management systems are suggested to reduce the risk of foetal losses. PMID- 26842364 TI - Equine encephalosis in Thoroughbred foals on a South African stud farm. AB - Thoroughbred foal body temperature data were collected from shortly after birth until shortly after weaning during the 2007/2008 season on a stud farm in the Western Cape Province of South Africa. Equine encephalosis (EE) caused by EE virus (EEV) serotype 4 (EEV-4) occurred in the foal group during the first autumn after their birth (March and April 2008). A descriptive study was undertaken to provide data on the EEV maternal antibody status, the association between pyrexia and EEV infection, and the incidence of infection amongst the foals prior to and during the episode. This included the frequent capturing of foal body temperature data and regular collection of serum and whole blood during pyretic episodes. Infection by EEV was determined using both virological and serological methods. A high EE incidence of at least 94% occurred amongst the foal cohort, despite the fact that 37% of foals had previously shown maternal antibody to EEV-4. Pyrexia in foals was not directly associated with EE infection and 41% of infected foals showed no detectable pyretic episode. Information obtained from this EE episode showed the high incidence of EEV infection in foals during the first autumn after their birth. Monitoring foal body temperature can alert farmers to outbreaks of infectious disease, such as EE. These results are relevant to the epidemiology of EE and facilitate greater understanding of it as a differential diagnosis of African horse sickness (AHS), given that EE and AHS have similar epidemiologic profiles. PMID- 26842365 TI - The prevalence of antibodies to Toxoplasma gondii in sheep in the Western Cape, South Africa. AB - The seroprevalence of Toxoplasma gondii antibodies in a sample of 292 merino sheep farmed in a semi-intensive manner in the Overberg region of the Western Cape, South Africa, was investigated. Antibody seroprevalence was determined by enzyme-linked immunosorbent assay. Of the total sample, 23 sheep tested positive for T. gondii antibodies (8%; 95% CI: 4.7688-10.9846). There was no statistically significant relationship between seroprevalence and age of the sheep. The highest seroprevalence was found in sheep between 28 and 40 months old; a total of 19 sheep were seropositive by 40 months. No seropositive sheep were found in the age group between 16 and 28 months. The seroprevalence reported in this study is higher than what has previously been reported for the Western Cape (6%) and across South Africa on average (4.7%). As sheep farming is economically significant in South Africa, the presence of T. gondii amongst sheep may pose a production threat to the small-stock industry as well as to public health and food security. We therefore recommend further surveillance to identify high-risk animal populations so that local control measures can be put in place. PMID- 26842366 TI - Determination of oxytetracycline residues in cattle meat marketed in the Kilosa district, Tanzania. AB - Oxytetracycline is used to treat various diseases in cattle. However, its use may be associated with unacceptable residue levels in food. Oxytetracycline residues in tissues from indigenous cattle were determined in a cross-sectional study conducted in the Kilosa district, Tanzania, between November 2012 and April 2013. A total of 60 tissue samples, including muscle, liver and kidney, were collected from slaughterhouses and butchers and analysed for oxytetracycline using high performance liquid chromatography. Oxytetracycline residues were found in 71.1% of the samples, of which 68.3% were above acceptable regulatory levels. The mean concentration of oxytetracycline across tissues was 3401.1 MUg/kg +/- 879.3 MUg/kg; concentrations in muscle, liver and kidney were 2604.1 MUg/kg +/- 703.7 MUg/kg, 3434.4 MUg/kg +/- 606.4 MUg/kg and 3533.1 MUg/kg +/- 803.6 MUg/kg, respectively. High levels of oxytetracycline residue in meat from indigenous cattle may pose a health threat to consumers in Kilosa. The findings possibly reflect a general lack of implementation of recommended withdrawal periods, ignorance about drug use and lack of extension services. Strict regulation of the use of antimicrobial drugs in the livestock industry and associated testing of animal-derived food sources prior to marketing are required. PMID- 26842367 TI - Investigation of multidrug-resistant fatal colisepticaemia in weanling pigs. AB - Escherichia coli is usually a benign commensal of the gut microflora. However, when E. coli acquires virulence genes it can multiply rapidly and cause disease through colonisation of the intestinal mucosa. Escherichia coli can become a significant pathogen in young pigs. We report an investigation of fatal colisepticaemia in weanling pigs from emerging farms where piglets and weaners were diarrhoeic and the mortality rate ranged between 15% and 70% in each litter. Faecal and tissue samples were processed for histopathology, bacteriology and molecular biology (multiplex and monoplex polymerase chain reaction) and we recovered enteroaggregative multidrug-resistant E. coli producing EAST-1 enterotoxin. An association between poor housing conditions and the observed cases was established and future management programmes were recommended to reduce the impact of such pathogens. Enteroaggregative E. coli is becoming a major problem in the pig industry. It therefore becomes necessary to establish the full impact of E. coli on the South African pig industry and to determine the geographic extent of the problem. PMID- 26842368 TI - Mesoscale atmospheric transport of ragweed pollen allergens from infected to uninfected areas. AB - Allergenic ragweed (Ambrosia spp.) pollen grains, after being released from anthers, can be dispersed by air masses far from their source. However, the action of air temperature, humidity and solar radiation on pollen grains in the atmosphere could impact on the ability of long distance transported (LDT) pollen to maintain allergenic potency. Here, we report that the major allergen of Ambrosia artemisiifolia pollen (Amb a 1) collected in ambient air during episodes of LDT still have immunoreactive properties. The amount of Amb a 1 found in LDT ragweed pollen grains was not constant and varied between episodes. In addition to allergens in pollen sized particles, we detected reactive Amb a 1 in subpollen sized respirable particles. These findings suggest that ragweed pollen grains have the potential to cause allergic reactions, not only in the heavily infested areas but, due to LDT episodes, also in the regions unaffected by ragweed populations. PMID- 26842369 TI - Different adaptations of Chinese winter-over expeditioners during prolonged Antarctic and sub-Antarctic residence. AB - Prolonged residence in Antarctica is characterized by exposure to isolated, confined, and extreme (ICE) environment. Winter-over expeditioners at research stations often exhibit a complex of psychophysiological symptoms, which varied by stations and sociocultural backgrounds. To understand the different patterns of psychophysiological responses provoked by environmental stress, we conducted a longitudinal assessment of mood and endocrine function in two groups of Chinese expeditioners who were deployed to sub-Antarctic (Great Wall Station, 62 degrees S, N = 12) and Antarctic (Zhongshan Station, 66 degrees S, N = 16) from December 2003 to 2005. Measures of mood, thyroid function, the levels of plasma catecholamine, and circulating interleukins were obtained at departure from China, mid-winter (Antarctica), end of winter (Antarctica), and return to China, respectively. The Zhongshan Station crew experienced significant increases in fatigue, anger, tension, confusion, and decrease in free thyroxine (FT4), norepinephrine (NE), and epinephrine (E) during the winter, increase in thyrotropin (TSH) and total triiodothyronine (TT3) when returning, whereas their counterparts at Great Wall Station only experienced increased TT3 after deployment. Moreover, compared with the Great Wall Station crew, the Zhongshan Station crew exhibited greater increase in anger, greater decrease in FT4, total thyroxine (TT4), NE and E over the winter, and greater increase in TSH when returning. Chinese expeditioners who lived and worked at the Antarctic station and the sub-Antarctic station for over a year showed different change patterns in mood and endocrine hormones. Negative mood and endocrine dysfunction were positively associated with the severity of environment. The study is a supplement to scientific knowledge on psychophysiological variation under ICE environment, which has certain applied value for the development of preventive countermeasures or interventions. PMID- 26842370 TI - Epithelioid angiosarcoma arising in schwannoma of the kidney: report of the first case and review of the literature. AB - BACKGROUND: Schwannoma and angiosarcoma are infrequent pathologies that have been rarely reported in the kidney. Angiosarcoma is an uncommon malignant tumor presenting a recognizable vascular differentiation. It can develop in any site but the most common locations include the skin, soft tissues, breast, bone, liver, and spleen while renal localization has been very rarely reported in the literature. Schwannoma is a benign peripheral nerve sheath tumor composed of cells with the immunophenotype and ultrastructural features of differentiated Schwann cells. It has a wide anatomical distribution but the most frequent locations include subcutaneous tissues of the extremities and the head and neck region and the retroperitoneal and mediastinal soft tissues. The occurrence of an angiosarcoma in a pre-existing schwannoma is an extremely rare event with <20 cases reported in worldwide literature. In the present study, a renal case of angiosarcoma arising in schwannoma is presented with a detailed review of the pertinent literature. CASE PRESENTATION: A 56-year-old man was admitted with a few days history of lower back pain and hematuria. Abdominal ultrasound showed a mass inside the left renal medulla. Subsequent imaging investigations with computed tomography and magnetic resonance confirmed the presence of the lesion and showed a pulmonary metastasis. CONCLUSIONS: The final histopathological examination led to the diagnosis of epithelioid angiosarcoma arising in a schwannoma. The patient came to death a few months later due to a massive hemothorax. To the best of our knowledge, the present is the first case of an angiosarcoma arising in a schwannoma of the kidney. PMID- 26842371 TI - beta-adrenergic receptor signalling and its functional consequences in the diseased heart. AB - BACKGROUND: To maintain the balance between the demand of the body and supply (cardiac output), cardiac performance is tightly regulated via the parasympathetic and sympathetic nervous systems. In heart failure, cardiac output (supply) is decreased due to pathologic remodelling of the heart. To meet the demands of the body, the sympathetic system is activated and catecholamines stimulate beta-adrenergic receptors (beta-ARs) to increase contractile performance and cardiac output. Although this is beneficial in the acute phase, chronic beta-ARs stimulation initiates a cascade of alterations at the cellular level, resulting in a diminished contractile performance of the heart. MATERIALS AND METHODS: This narrative review includes results from previously published systematic reviews and clinical and basic research publications obtained via PubMed up to May 2015. RESULTS: We discuss the alterations that occur during sustained beta-AR stimulation in diseased myocardium and emphasize the consequences of beta-AR overstimulation for cardiac function. In addition, current treatment options as well as future therapeutic strategies to treat patients with heart failure to normalize consequences of beta-AR overstimulation are discussed. CONCLUSIONS: The heart is able to protect itself from chronic stimulation of the beta-ARs via desensitization and reduced membrane availability of the beta-ARs. However, ultimately this leads to an impaired downstream signalling and decreased protein kinase A (PKA)-mediated protein phosphorylation. beta-blockers are widely used to prevent beta-AR overstimulation and restore beta ARs in the failing hearts. However, novel and more specific therapeutic treatments are needed to improve treatment of HF in the future. PMID- 26842372 TI - Comparison of the Automated cobas u 701 Urine Microscopy and UF-1000i Flow Cytometry Systems and Manual Microscopy in the Examination of Urine Sediments. AB - BACKGROUND: The cobas u 701, a new automated image-based urine sediment analyzer, was introduced recently. In this study, we compared its performance with that of UF-1000i flow cytometry and manual microscopy in the examination of urine sediments. METHODS: Precision, linearity, and carry-over were determined for the two urine sediment analyzers. For a comparison of the method, 300 urine samples were examined by the automated analyzers and by manual microscopy using a KOVA chamber. RESULTS: Within-run coefficients of variation (CVs) for the control materials were 7.0-8.8% and 1.7-5.7% for the cobas u 701 and UF-1000i systems, respectively. Between-run CVs were 8.5-9.8% and 2.7-5.4%, respectively. Both instruments showed good linearity and negligible carry-over. For red blood cells (RBC), white blood cells (WBC), and epithelial cells (EPI), the overall concordance rates within one grade of difference among the three methods were good (78.6-86.0%, 88.7-93.8%, and 81.3-90.7%, respectively). The concordance rate for casts was poor (66.5-68.9%). CONCLUSION: Compared with manual microscopy, the two automated sediment analyzers tested in this study showed satisfactory analytical performances for RBC, WBC, and EPI. However, for other urine sediment particles confirmation by visual microscopy is still required. PMID- 26842373 TI - Can we assess the risk of embolic complications of cardioversion? PMID- 26842374 TI - Four good reasons to appreciate triple positivity. PMID- 26842375 TI - Heart failure with preserved ejection fraction. PMID- 26842376 TI - Transmission of tuberculosis among people living in the border areas of Poland, the Czech Republic, and Slovakia. AB - INTRODUCTION: In 2007, Poland, the Czech Republic, and Slovakia joined the Schengen Agreement, abolishing restrictions on people crossing the borders. Currently, these areas are places of population movements for economic, family, and touristic reasons. This favors the transmission of infectious diseases, including tuberculosis, and requires enhanced control over the spread of the source of infection in the population of patients living in the border areas. OBJECTIVES: The aim of this study was to investigate the genetic relatedness among Mycobacterium tuberculosis complex strains isolated from patients living in 3 border areas: Poland, the Czech Republic, and Slovakia. PATIENTS AND METHODS The study group consisted of 209 patients with tuberculosis diagnosed and treated between 2007 and 2011 in health care facilities in the Silesia Province in Poland (121 patients [58%]), Zilina in Slovakia (57 [27%]), and the Moravian-Silesian Region in the Czech Republic (31 [15%]). Genotyping of strains was performed using spoligotyping and IS6110-Mtb1-Mtb2 polymerase chain reaction. RESULTS: Among 209 strains, 23 molecular families (clusters) were identified. Seventeen clusters were identified as national. Six international clusters consisted of 30 strains isolated from patients of various nationalities. CONCLUSIONS: We identified 6 potential outbreaks of tuberculosis transmission between patients of different nationalities. The circumstances favorable to potential contacts of patients included mainly travelling to the neighboring countries, hospital stays, and addictions. However, there was no evidence of an epidemiological link between these patients, so it may be assumed that if they had come in contact with one another, it was accidental. We observed that the greater incidence of tuberculosis on the Polish territory did not affect the incidence in the Czech Republic or Slovakia over the analysis period. PMID- 26842377 TI - Association between microRNA-21 concentration and lipid profile in patients with acute coronary syndrome without persistent ST-segment elevation. AB - INTRODUCTION: MicroRNA (miRNAs) are noncoding RNAs involved in the regulation of gene expression. Certain miRNAs, especially miRNA-21 (miR-21), may be involved in lipid metabolism. OBJECTIVES: The aim of the study was to evaluate the association between plasma free circulating miR-21 levels and lipid fractions: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, and triglycerides (TG), as well as their atherogenic profile expressed as the ratio of individual lipid fractions (TC:LDL-C, TC:non-HDL-C, TG:HDL-C, and HDL-C:LDL-C) in patients with acute coronary syndromes without persistent ST -segment elevation (NSTE ACS). PATIENTS AND METHODS: The study group consisted of 34 patients diagnosed with NSTE ACS on admission to the emergency department. Plasma miRNA levels were determined by real-time polymerase chain reaction and the DeltaDeltaCt method. Serum lipid fractions were assessed after a minimum of 12-hour fasting during the first day of hospitalization. RESULTS: MiR-21 levels showed a significant inverse correlation with TC (r = -0.5; P = 0.002), LDLC (r = -0.5; P = 0.001), and non HDL-C (r = -0.6; P <0.001) levels. Moreover, they were inversely correlated with TC:HDL-Cratio (r = -0.6; P <0.001), LDL-C:HDL-Cratio (r = -0.6; P <0.001), TG:HDL Cratio (r = -0.4; P = 0.037), and TC:non-HDLratio (r = 0.6; P <0.001). In a multivariate analysis, miR-21 levels (beta = -0.41; P = 0.018) and the need for revascularization (beta = 0.35; P = 0.027) were independent predictors of non-HDL C levels. CONCLUSIONS: Free circulating miR-21 levels inversely correlate with TC, LDL-C, and non-HDL-C and are an independent predictor of non-HDL-C levels in patients with NSTE ACS. Thus, the overexpression of miR-21 is associated with a less atherogenic lipid profile. PMID- 26842378 TI - Beneficial effect of bilateral native nephrectomy as complete denervation on left ventricular mass and function in renal transplant recipients. AB - INTRODUCTION: Left ventricular hypertrophy (LVH) is a risk factor for cardiovascular morbidity and mortality in renal transplant recipients. The development of LVH is connected with excessive activation of the sympathetic nervous system. A bilateral nephrectomy is an example of complete renal denervation. OBJECTIVES: The aim of this study was to evaluate the effect of pretransplant bilateral native nephrectomy on left ventricular mass and function during a long-term follow-up of patients after kidney transplantation. PATIENTS AND METHODS: The study group consisted of 32 renal transplant recipients who had previously undergone pretransplant bilateral native nephrectomy. The control group involved 32 recipients with preserved native kidneys, matched for age, sex, creatinine levels, estimated glomerular filtration rate, immunosuppressive treatment, and the time of renal replacement therapy. All patients were evaluated by echocardiography, and 16 patients--by cardiac magnetic resonance (CMR). In addition, all patients had their arterial blood pressure (BP) and metabolic markers measured. RESULTS: In comparison with controls, the study group had lower systolic BP (P = 0.048) and received a lower number of antihypertensive agents (P = 0.001). Lipid and hemoglobin levels were similar in both groups. The study group had a lower left ventricular mass index (LVMI; P = 0.001) and left atrial volume index (LAVI; P = 0.004). The left ventricular mass evaluated by CMR was also lower in the study group (P <0.001). Mild left ventricular diastolic dysfunction (LVDD) was more frequent in the study group compared with the control group ( P <0.001). CONCLUSIONS: In a long-term follow-up of patients after kidney transplantation, the bilateral native nephrectomy before transplantation was associated with a lower LVMI and LAVI as well as a lower grade of LVDD. These patients had lower systolic BP and used fewer antihypertensive drugs. PMID- 26842379 TI - Bradykinin-mediated angioedema. AB - Angioedema and urticaria often constitute a challenge in daily clinical practice. They may either co- -occur or present as independent conditions. They are characterized by a complex pathomechanism, and their symptoms may be triggered by diverse factors. These differences are crucial for developing a successful treatment regimen. Both conditions may have an allergic origin (immunoglobulin [Ig] E and non-IgE-related), usually induced by histamine, or a nonallergic one, such as bradykinin-mediated angioedema in patients with C1 inhibitor (C1-INH) deficiency or angioedema induced by certain drugs (eg, angiotensin-converting enzyme inhibitors). Currently, we distinguish 5 types of nonallergic angioedema: hereditary angioedema (HAE) due to C1-INH deficiency, acquired angioedema (AAE), and angioedema induced by the renin-angiotensin-aldosterone system, all of which are mediated by bradykinin, as well as pseudoallergic angioedema and idiopathic angioedema. Bradykinin-mediated angioedema (eg, laryngeal angioedema) may be life threatening because of resistance to corticosteroids and antihistamine drugs. C1 INH concentrates are the drugs of choice in the treatment of HAE and AAE. In recent years, some new drugs have been introduced in the treatment of bradykinin mediated angioedema, such as bradykinin B2-receptor antagonist, icatibant, and kallikrein inhibitor, ecallantide, which allow to improve treatment outcomes. PMID- 26842380 TI - Staged treatment of central and peripheral lesions in chronic thromboembolic pulmonary hypertension. PMID- 26842381 TI - A solitary skin metastasis in renal cell carcinoma. PMID- 26842382 TI - A cross-sectional study of dentine sensitivity in periodontitis patients in Trinidad and Tobago. AB - OBJECTIVE: This cross-sectional study aimed to determine the prevalence, distribution and associated factors of dentine sensitivity (DS) among periodontitis patients in Trinidad. METHODS: Sequential patients meeting the periodontitis criteria (BPE 4/4*) were included and completed a questionnaire on DS prior to a full periodontal examination. Clinically elicited symptoms of DS and presence of cervical tooth wear were recorded. RESULTS: DS prevalence was 73.1% (n = 130; mean age 50 years). Mean number of sensitive teeth increased with increased severity of gingival recession. Most common initiating factors of DS were cold stimuli (70.5%), brushing (25.3%) and sour food (11.6%). Correlations were obtained for DS and race, toothbrush texture hardness, cervical tooth wear and gingival recession severity (P < 0.05; binary logistic regression). Cervical tooth wear was recorded in 46.3% of DS patients. Full-mouth plaque scores (FMPS) and full-mouth bleeding scores (FMBS) were statistically significantly (P < 0.05; Mann-Whitney U) test lower for DS versus non-DS patients. Patients reported a low usage (27.4%) and satisfaction (53.8%) rating for desensitizing agents. CONCLUSIONS: The high prevalence of DS was comparable to other studies on periodontitis patients. Progressive periodontal disease and toothbrush abrasion were possible aetiological factors for DS in this study. Knowledge of local dietary practices and the role of acidic (sour) foods in eliciting DS may aid in management. The high prevalence of cervical tooth wear and the lower FMPS and FMBS among DS patients may reflect more aggressive tooth brushing. DS does not seem to be a limitation to plaque control in DS versus non-DS patients in this study. PMID- 26842383 TI - A review of the new HGNC gene family resource. AB - The HUGO Gene Nomenclature Committee (HGNC) approves unique gene symbols and names for human loci. As well as naming genomic loci, we manually curate genes into family sets based on shared characteristics such as function, homology or phenotype. Each HGNC gene family has its own dedicated gene family report on our website, www.genenames.org . We have recently redesigned these reports to support the visualisation and browsing of complex relationships between families and to provide extra curated information such as family descriptions, protein domain graphics and gene family aliases. Here, we review how our gene families are curated and explain how to view, search and download the gene family data. PMID- 26842384 TI - Geographical distribution of protozoan and metazoan parasites of farmed Nile tilapia Oreochromis niloticus (L.) (Perciformes: Cichlidae) in Yucatan, Mexico. AB - BACKGROUND: In Yucatan State, southern Mexico, as in many other parts of the world where tilapia has been introduced for aquaculture, the deficient application of management measures has led to the establishment of non-native parasites. The aims of this study were to describe the geographical distribution of protozoan and helminth parasites of farmed Nile tilapia Oreochromis niloticus (L.) throughout the Yucatan and to examine the potential statistical associations of the prevalence and mean abundance of these parasites with management and environmental variables. METHODS: All 29 Nile tilapia farms currently operating in Yucatan were surveyed. Maps were created to describe the geographical location of the parasites infecting Nile tilapia at each farm. We evaluated the statistical associations of management and environmental variables with the mean abundance values of each parasite species using a multivariate redundancy analysis (RDA) and generalized additive models (GAM). We also used Ripley's K to determine whether there were significant clusters of the mean abundance of particular parasite species in specific regions of the Yucatan State. RESULTS: A total of 580 O. niloticus were examined, and 11 species of parasites were recorded. Cichlidogyrus sclerosus was the most frequent and abundant parasite at all 29 farms, whereas Gyrodactylus cichlidarum was found in 26 of the 29 farms. The RDA showed that the most important predictors were the concentration of nitrites and ammonium and the water exchange rate. The GAM showed the significant effect of the tank capacity, no use of quarantine area and no use of prophylactic treatments on the mean abundance of G. cichlidarum. The geographical distribution patterns of the mean abundance of most parasite species exhibited clustering near to the coast of Yucatan. CONCLUSION: Two groups of farms were distinguished: (i) farms with medium to high technology, where the most frequent and abundant parasite was G. cichlidarum, and (ii) farms with low technology, where the most frequent and abundant parasite was C. sclerosus. Good biosecurity practices such as the use of quarantine and prophylactic treatments prior to the introduction of infected Nile tilapia to the farms are recommended to avoid the establishment of parasites such as G. cichlidarum in farms. PMID- 26842385 TI - A Man With Persistent Dopamine Agonist Withdrawal Syndrome After 7 Years Being Off Dopamine Agonists. PMID- 26842386 TI - Courtship Pheromone Use in a Model Urodele, the Mexican Axolotl (Ambystoma mexicanum). AB - Sex pheromones have been shown to constitute a crucial aspect of salamander reproduction. Until now, courtship pheromones of Salamandridae and Plethodontidae have been intensively studied, but information on chemical communication in other urodelan families is essentially lacking. The axolotl (Ambystoma mexicanum, Ambystomatidae) has a courtship display that suggests a key role for chemical communication in the orchestration of its sexual behavior, but no sex pheromones have yet been characterized from this species. Here we combined whole transcriptome analyses of the male cloaca with proteomic analyses of water in which axolotls were allowed to court to show that male axolotls secrete multiple ca. 20 kDa glycosylated sodefrin precursor-like factor (SPF) proteins during courtship. In combination with phylogenetic analyses, our data show that the male cloaca essentially secretes a courtship-specific clade of SPF proteins that is orthologous to salamandrid courtship pheromones. In addition, we identified an SPF protein for which no orthologs have been described from other salamanders so far. Overall, our study advocates a central role for SPF proteins during the courtship display of axolotls and adds knowledge on pheromone use in a previously unexplored deep evolutionary branch of salamander evolution. PMID- 26842387 TI - Rolapitant for the treatment of chemotherapy-induced nausea and vomiting: a review of the clinical evidence. AB - Chemotherapy-induced nausea and vomiting (CINV), both acute and delayed, has a dramatic effect on the well-being and quality of life of patients with cancer. Improved understanding of the mechanisms involved in CINV has led to the development of agents targeting the 5-HT3 receptor as well as the NK-1 receptor. Antiemetic prophylaxis given to patients receiving highly emetogenic chemotherapy combines agents blocking the 5-HT3 and NK-1 receptors along with corticosteroids given regularly and repeatedly. Rolapitant is a long-acting NK-1 receptor antagonist with proven efficacy in controlling CINV as part of the prophylaxis regimen. This review will detail the clinical efficacy and safety of rolapitant in the treatment of patients with cancer receiving highly or moderately emetogenic chemotherapy. PMID- 26842388 TI - The foot function index is more sensitive to change than the Leeds Foot Impact Scale for evaluating rheumatoid arthritis patients after forefoot or hindfoot reconstruction. AB - PURPOSE: This study examines the responsiveness of the Foot Functional Index (FFI) and Leeds Foot Impact Scale for Rheumatoid Arthritis (LFIS-RA) in rheumatoid arthritis (RA) patients receiving a forefoot or hindfoot reconstruction. METHODS: This was a prospective cohort study including 30 rheumatoid arthritis patients with severe rheumatoid foot deformities in need for surgical correction. Responsiveness was measured using distribution-based methods (standardized effect size, standardized response mean and Guyatt responsiveness ratio) and anchor-based methods (receiver operating characteristics curves and correlation analyses) by making use of an anchor question. To examine the depth of the questionnaires we measured the floor and ceiling effects. RESULTS: The study population consisted of three males and 27 females, with a mean age of 62 years. The mean follow-up time was 38 months. Twenty-two feet received a forefoot reconstruction and eight feet a triple arthrodesis. For the FFI the SES was 0.80, SRM was -0.85 and the GRR was -1.25. For the LFIS-RA the SES was 0.58, SRM was 0.58 and the GRR was 0.88. The AUC was 0.741 and 0.645 for FFI and LFIS, respectively. Contrary to the LFIS-RA, the FFI showed a significant correlation between change score and the anchor question. Both questionnaires did not show a significant floor or ceiling effect. CONCLUSION: The FFI showed a large responsiveness and the LFIS- RA showed moderate responsiveness in rheumatoid arthritis patients receiving forefoot or hindfoot surgery, without floor or ceiling effects in both questionnaires. PMID- 26842390 TI - Temperature- and Turbidity-Dependent Competitive Interactions Between Invasive Freshwater Mussels. AB - We develop a staged-structured population model that describes the competitive dynamics of two functionally similar, congeneric invasive species: zebra mussels and quagga mussels. The model assumes that the population survival rates are functions of temperature and turbidity, and that the two species compete for food. The stability analysis of the model yields conditions on net reproductive rates and intrinsic growth rates that lead to competitive exclusion. The model predicts quagga mussel dominance leading to potential exclusion of zebra mussels at mean water temperatures below [Formula: see text] and over a broad range of turbidities, and a much narrower set of conditions that favor zebra mussel dominance and potential exclusion of quagga mussels at temperatures above [Formula: see text] and turbidities below 35 NTU. We then construct a two-patch dispersal model to examine how the dispersal rates and the environmental factors affect competitive exclusion and coexistence. PMID- 26842389 TI - Dynamics of an HIV Model with Multiple Infection Stages and Treatment with Different Drug Classes. AB - Highly active antiretroviral therapy can effectively control HIV replication in infected individuals. Some clinical and modeling studies suggested that viral decay dynamics may depend on the inhibited stages of the viral replication cycle. In this paper, we develop a general mathematical model incorporating multiple infection stages and various drug classes that can interfere with specific stages of the viral life cycle. We derive the basic reproductive number and obtain the global stability results of steady states. Using several simple cases of the general model, we study the effect of various drug classes on the dynamics of HIV decay. When drugs are assumed to be 100% effective, drugs acting later in the viral life cycle lead to a faster or more rapid decay in viremia. This is consistent with some patient and experimental data, and also agrees with previous modeling results. When drugs are not 100% effective, the viral decay dynamics are more complicated. Without a second population of long-lived infected cells, the viral load decline can have two phases if drugs act at an intermediate stage of the viral replication cycle. The slopes of viral load decline depend on the drug effectiveness, the death rate of infected cells at different stages, and the transition rate of infected cells from one to the next stage. With a second population of long-lived infected cells, the viral load decline can have three distinct phases, consistent with the observation in patients receiving antiretroviral therapy containing the integrase inhibitor raltegravir. We also fit modeling prediction to patient data under efavirenz (a nonnucleoside reverse transcriptase inhibitor) and raltegravir treatment. The first-phase viral load decline under raltegravir therapy is longer than that under efavirenz, resulting in a lower viral load at initiation of the second-phase decline in patients taking raltegravir. This explains why patients taking a raltegravir-based therapy were faster to achieve viral suppression than those taking an efavirenz-based therapy. Taken together, this work provides a quantitative and systematic comparison of the effect of different drug classes on HIV decay dynamics and can explain the viral load decline in HIV patients treated with raltegravir containing regimens. PMID- 26842391 TI - Nonnuclear Attractors in Heteronuclear Diatomic Systems. AB - Nonnuclear attractors (NNAs) are observed in the electron density of a variety of systems, but the factors governing their appearance and their contribution to the system's properties remain a mystery. The NNA occurring in homo- and heteronuclear diatomics of main group elements with atomic numbers up to Z = 38 is investigated computationally (at the UCCSD/cc-pVQZ level of theory) by varying internuclear separations. This was done to determine the NNA occurrence window along with the evolution of the respective pseudoatomic basin properties. Two distinct categories of NNAs were detected in the data analyzed by means of catastrophe theory. Type "a" implies electronic charge transfer between atoms mediated by a pseudoatom. Type "b" shows an initial relocation of some electronic charge to a pseudoatom, which posteriorly returns to the same atom that donated this charge in the first place. A small difference of polarizability between the atoms that compose these heteronuclear diatomics seems to favor NNA formation. We also show that the NNA arising tends to result in some perceptible effects on molecular dipole and/or quadrupole moment curves against internuclear distance. Finally, successive cationic ionization results in the fast disappearance of the NNA in Li2 indicating that its formation is mainly governed by the field generated by the quantum mechanical electronic density and only depends parametrically on the bare nuclear field/potential at a given molecular geometry. PMID- 26842392 TI - Tailoring Electrical Transport Across Metal-Thermoelectric Interfaces Using a Nanomolecular Monolayer. AB - We report a 13-fold increase in electrical contact conductivity Sigmac upon introducing a 1,8-octanedithiol (ODT) monolayer at Cu-Bi2Te3 interfaces. In contrast introducing ODT at Ni-Bi2Te3 interfaces results in a 20% decrease in Sigmac. Rutherford backscattering spectrometry, X-ray diffraction and electron spectroscopy analyses indicate that metal-sulfur and sulfur-Bi2Te3 bonds at metal Bi2Te3 interfaces inhibit chemical mixing, curtail metal-telluride formation, and suppress oxidation. Suppressing p-type Cu2Te favors electrical transport across Cu-metallized n-type Bi2Te3, whereas inhibiting the formation of Ohmic-contact promoting NixTey compromises the electrical conductance at Ni-Bi2Te3 interfaces. Our findings illustrate that molecular nanolayers could be attractive for manipulating interface chemistry and phase formation for tailoring electrical transport across metal-thermoelectric interfaces for solid-state refrigeration applications. PMID- 26842394 TI - Development of a serum-free liquid medium for Bartonella species. AB - The genus Bartonella comprises numerous species with at least 13 species pathogenic for humans. They are fastidious, aerobic, Gram negative, and facultative intracellular bacteria which cause a variety of human and non-human diseases. This study focused on the development of a serum-free liquid medium for culture of Bartonella species. Some liquid media are available commercially but all of them use undefined supplements such as fetal calf serum or defibrinated sheep blood. Our intention was to create a reproducible liquid medium for Bartonella species that can simply be prepared. We tested several supplements that could potentially support the growth of Bartonella species. Slight growth improvement was achieved with glucose and sucrose. However, hemin in particular improved the growth rate. At a temperature of 37 degrees C, a CO2 concentration of 5 %, a humidified atmosphere, and the use of the supplements glucose, sucrose, and hemin, we developed a medium that does not need serum as an undefined supplement any more. In conclusion, the newly developed medium supports growth of Bartonella species equal to the commercially available media but with the advantage that it has a serum-free formulation. It can be prepared fast and easy and is a useful tool in studying these bacteria. PMID- 26842393 TI - Microbial metabolomics in open microscale platforms. AB - The microbial secondary metabolome encompasses great synthetic diversity, empowering microbes to tune their chemical responses to changing microenvironments. Traditional metabolomics methods are ill-equipped to probe a wide variety of environments or environmental dynamics. Here we introduce a class of microscale culture platforms to analyse chemical diversity of fungal and bacterial secondary metabolomes. By leveraging stable biphasic interfaces to integrate microculture with small molecule isolation via liquid-liquid extraction, we enable metabolomics-scale analysis using mass spectrometry. This platform facilitates exploration of culture microenvironments (including rare media typically inaccessible using established methods), unusual organic solvents for metabolite isolation and microbial mutants. Utilizing Aspergillus, a fungal genus known for its rich secondary metabolism, we characterize the effects of culture geometry and growth matrix on secondary metabolism, highlighting the potential use of microscale systems to unlock unknown or cryptic secondary metabolites for natural products discovery. Finally, we demonstrate the potential for this class of microfluidic systems to study interkingdom communication between fungi and bacteria. PMID- 26842395 TI - Expression of ustR and the Golgi protease KexB are required for ustiloxin B biosynthesis in Aspergillus oryzae. AB - Ustiloxin B, originally isolated from the fungus Ustilaginoidea virens, is a known inhibitor of microtubule assembly. Ustiloxin B is also produced by Aspergillus flavus and is synthesized through the ribosomal peptide synthesis pathway. In A. flavus, the gene cluster associated with ustiloxin B production contains 15 genes including those encoding a fungal C6-type transcription factor and ustiloxin B precursor. Although the koji mold Aspergillus oryzae, which is genetically close to A. flavus, has the corresponding gene cluster, it does not produce ustiloxin B, which may be explained by the fact that the gene encoding the transcription factor UstR is not expressed. Here, to investigate whether ustiloxin B can be produced by expressing ustR in A. oryzae, we constructed ustR expression (ustR (EX)) strains and analyzed ustiloxin B production. In the ustR (EX) strains, all genes in the cluster were up-regulated, in line with expression of ustR, and ustiloxin B produced. To elucidate whether the KexB protease is involved in the processing of the ustiloxin B precursor protein UstA, which has repeats of basic amino acid doublets resembling KexB target sites, we also constructed a ustR (EX) strain with the ?kexB genotype. Although ustR was expressed in this strain, ustiloxin B was barely detectable. This finding strongly suggests that KexB is required for ustiloxin B production. PMID- 26842396 TI - Endurance exercise ameliorates low birthweight developed catch-up growth related metabolic dysfunctions in a mouse model. AB - Low birthweight is known to predict high risk of metabolic diseases in adulthood, while regular endurance exercises are believed sufficient to improve metabolic dysfunction. In this study, we established a mouse model to determine whether long-term exercise training could ameliorate catch-up growth, and we explored the possible underlying mechanisms. By restricting maternal food intake during the last week of gestation, we successfully produced low birthweight pups. Further, normal birthweight mice and low birthweight mice were randomly distributed into one of three groups receiving either a normal fat diet, high fat diet, or high fat diet with exercise training. The growth/metabolism, mitochondrial content and functions were assessed at 6 months of age. Through group comparisons and correlation analyses, the 4th week was demonstrated to be the period of crucial growth and chosen to be the precise point of intervention, as the growth rate at this point is significantly correlated with body weight, intraperitoneal glucose tolerance test (IPGTT), Lee's index and fat mass in adulthood. In addition, regular endurance exercises when started from 4 weeks remarkably ameliorated low birthweight outcomes and induced catch-up growth and glucose intolerance in the 25th week. Furthermore, real-time PCR and western blot results indicated that the effect of long-term exercise on mitochondrial functions alleviated catch-up related metabolic dysfunction. To conclude, long-term exercise training from the 4th week is sufficient to ameliorate catch-up growth and related metabolic disturbances in adulthood by promoting mitochondrial functions in skeletal muscle. PMID- 26842397 TI - Oral clomethiazole treatment for paediatric non-convulsive status epilepticus. AB - We report a retrospective case study of the use of clomethiazole for treatment of non-convulsive status epilepticus in a patient not responding to benzodiazepines, illustrated by EEG and video. Clomethiazole can be considered as a safe oral option for management of non-convulsive status epilepticus when conventional treatment has failed. [Published with video sequences online]. PMID- 26842398 TI - Welfare States, Labor Markets, Political Dynamics, and Population Health: A Time Series Cross-Sectional Analysis Among East and Southeast Asian Nations. AB - Recent scholarship offers different theories on how macrosocial determinants affect the population health of East and Southeast Asian nations. Dominant theories emphasize the effects of welfare regimes, welfare generosity, and labor market institutions. In this article, we conduct exploratory time-series cross sectional analyses to generate new evidence on these theories while advancing a political explanation. Using unbalanced data of 7 East Asian countries and 11 Southeast Asian nations from 1960 to 2012, primary findings are 3-fold. First, welfare generosity measured as education and health spending has a positive impact on life expectancy, net of GDP. Second, life expectancy varies significantly by labor markets; however, these differences are explained by differences in welfare generosity. Third, as East and Southeast Asian countries become more democratic, welfare generosity increases, and population health improves. This study provides new evidence on the value of considering politics, welfare states, and labor markets within the same conceptual framework. PMID- 26842399 TI - Perinatal exposure to germinated brown rice and its gamma amino-butyric acid-rich extract prevents high fat diet-induced insulin resistance in first generation rat offspring. AB - BACKGROUND: Evidence suggests perinatal environments influence the risk of developing insulin resistance. OBJECTIVE: The present study was aimed at determining the effects of intrauterine exposure to germinated brown rice (GBR) and GBR-derived gamma (gamma) aminobutyric acid (GABA) extract on epigenetically mediated high fat diet-induced insulin resistance. DESIGN: Pregnant Sprague Dawley rats were fed high-fat diet (HFD), HFD+GBR, or HFD+GABA throughout pregnancy until 4 weeks postdelivery. The pups were weighed weekly and maintained on normal pellet until 8 weeks postdelivery. After sacrifice, biochemical markers of obesity and insulin resistance including oral glucose tolerance test, adiponectin, leptin, and retinol binding protein-4 (RBP4) were measured. Hepatic gene expression changes and the global methylation and histone acetylation levels were also evaluated. RESULTS: Detailed analyses revealed that mothers given GBR and GABA extract, and their offspring had increased adiponectin levels and reduced insulin, homeostasis model assessment of insulin resistance, leptin, oxidative stress, and RBP4 levels, while their hepatic mRNA levels of GLUT2 and IPF1 were increased. Furthermore, GBR and GABA extract lowered global DNA methylation levels and modulated H3 and H4 acetylation levels. CONCLUSIONS: These results showed that intrauterine exposure to GBR-influenced metabolic outcomes in offspring of rats with underlying epigenetic changes and transcriptional implications that led to improved glucose homeostasis. PMID- 26842401 TI - CrossTalk proposal: Interstitial cells are involved and physiologically important in neuromuscular transmission in the gut. PMID- 26842403 TI - Oxidative coupling between C(sp2)-H and C(sp3)-H bonds of indoles and cyclic ethers/cycloalkanes. AB - Cross-dehydrogenative-coupling (CDC) between C-H/C-H bonds of indoles and cyclic ethers/cycloalkanes is made viable through a simple transition-metal-free pathway. With the aid of only di-tert-butyl peroxide, a number of inactive cyclic ethers and cycloalkanes can be directly coupled with indole derivatives in satisfactory yields. PMID- 26842400 TI - Campylobacter jejuni and Campylobacter coli in wild birds on Danish livestock farms. AB - BACKGROUND: Reducing the occurrence of campylobacteriosis is a food safety issue of high priority, as in recent years it has been the most commonly reported zoonosis in the EU. Livestock farms are of particular interest, since cattle, swine and poultry are common reservoirs of Campylobacter spp. The farm environment provides attractive foraging and breeding habitats for some bird species reported to carry thermophilic Campylobacter spp. We investigated the Campylobacter spp. carriage rates in 52 wild bird species present on 12 Danish farms, sampled during a winter and a summer season, in order to study the factors influencing the prevalence in wild birds according to their ecological guild. In total, 1607 individual wild bird cloacal swab samples and 386 livestock manure samples were cultured for Campylobacter spp. according to the Nordic Committee on Food Analysis method NMKL 119. RESULTS: The highest Campylobacter spp. prevalence was seen in 110 out of 178 thrushes (61.8 %), of which the majority were Common Blackbird (Turdus merula), and in 131 out of 616 sparrows (21.3 %), a guild made up of House Sparrow (Passer domesticus) and Eurasian Tree Sparrow (Passer montanus). In general, birds feeding on a diet of animal or mixed animal and vegetable origin, foraging on the ground and vegetation in close proximity to livestock stables were more likely to carry Campylobacter spp. in both summer (P < 0.001) and winter (P < 0.001) than birds foraging further away from the farm or in the air. Age, fat score, gender, and migration range were not found to be associated with Campylobacter spp. carriage. A correlation was found between the prevalence (%) of C. jejuni in wild birds and the proportions (%) of C. jejuni in both manure on cattle farms (R(2) = 0.92) and poultry farms (R(2) = 0.54), and between the prevalence (%) of C. coli in wild birds and the proportions (%) of C. coli in manure on pig farms (R(2) = 0.62). CONCLUSIONS: The ecological guild of wild birds influences the prevalence of Campylobacter spp. through the behavioural patterns of the birds. More specifically, wild birds eating food of animal or mixed animal and vegetable origin and foraging on the ground close to livestock were more likely to carry Campylobacter spp. than those foraging further away or hunting in the air. These findings suggest that wild birds may play a role in sustaining the epidemiology of Campylobacter spp. on farms. PMID- 26842402 TI - Novel pseudo-random number generator based on quantum random walks. AB - In this paper, we investigate the potential application of quantum computation for constructing pseudo-random number generators (PRNGs) and further construct a novel PRNG based on quantum random walks (QRWs), a famous quantum computation model. The PRNG merely relies on the equations used in the QRWs, and thus the generation algorithm is simple and the computation speed is fast. The proposed PRNG is subjected to statistical tests such as NIST and successfully passed the test. Compared with the representative PRNG based on quantum chaotic maps (QCM), the present QRWs-based PRNG has some advantages such as better statistical complexity and recurrence. For example, the normalized Shannon entropy and the statistical complexity of the QRWs-based PRNG are 0.999699456771172 and 1.799961178212329e-04 respectively given the number of 8 bits-words, say, 16Mbits. By contrast, the corresponding values of the QCM-based PRNG are 0.999448131481064 and 3.701210794388818e-04 respectively. Thus the statistical complexity and the normalized entropy of the QRWs-based PRNG are closer to 0 and 1 respectively than those of the QCM-based PRNG when the number of words of the analyzed sequence increases. It provides a new clue to construct PRNGs and also extends the applications of quantum computation. PMID- 26842404 TI - Depletion of the LINC complex disrupts cytoskeleton dynamics and meiotic resumption in mouse oocytes. AB - The SUN (Sad-1/UNC-84) and KASH (Klarsicht/ANC-1/Syne/homology) proteins constitute the linker of nucleoskeleton and cytoskeleton (LINC) complex on the nuclear envelope. To date, the SUN1/KASH5 complex is known to function as meiotic specific factors. In this study, gene-silencing methods were used to explore the roles of SUN1 and KASH5 in mouse oocytes after prophase. SUN1 was detected throughout the nucleus; however, KASH5 was dispersed through the cell. After germinal vesicle breakdown (GVBD), SUN1 and KASH5 migrated during spindle formation and localized to the spindle poles at the MII stage. Most oocytes were arrested at the germinal vesicle (GV) stage after depletion of either SUN1 or KASH5. The DNA damage response was triggered in SUN1-depleted oocytes and thus gave rise to the G2/M checkpoint protein, p-CHK1. Oocytes that underwent GVBD had relatively small and abnormal spindles and lower levels of cytoplasm F-actin mesh. Immunofluorescence results also indicated the dislocation of pericentrin and P150(Glued) after SUN1 or KASH5 depletion. Furthermore, KASH5 localized exclusively near the oocyte cortex after SUN1 depletion, but SUN1 localization was unaffected in KASH5-depleted oocytes. Taken together, the results suggest that SUN1 and KASH5 are essential factors in the regulation of meiotic resumption and spindle formation. PMID- 26842406 TI - Effect of Body Mass Index on Complications and Reoperations After Total Hip Arthroplasty. AB - BACKGROUND: High body mass index (BMI) is associated with increased rates of complications after total hip arthroplasty. Studies to date have evaluated risk mainly as a dichotomous variable according to BMI thresholds. The purpose of this paper was to characterize the risk of complications and implant survival according to BMI as a continuous variable. METHODS: Using prospectively collected data from our institutional total joint registry, we analyzed 21,361 consecutive hips (17,774 patients) treated with primary total hip arthroplasty between 1985 and 2012 at a single institution. The average BMI at the time of surgery was 28.7 kg/m(2) (range, 15 to 69 kg/m(2)). Estimates of revision surgery and common complications associated with BMI were analyzed using the Kaplan-Meier method of assessing survivorship, with associations of outcomes assessed using a Cox model. RESULTS: Utilizing smoothing spline parameterization, we found that reoperation (p < 0.001) and implant revision or removal rates (p = 0.002) increased with increasing BMI. Increasing BMI was associated with increased rates of early hip dislocation (p = 0.02), wound infection, and, most strikingly, deep periprosthetic infection (a hazard ratio of 1.09 per unit of BMI >25 kg/m(2); p < 0.001). However, we found no association between increasing BMI and any revision for mechanical failure of the implant or between increasing BMI and revision for aseptic implant loosening. There was an inverse correlation between increasing BMI and risk of revision for bearing wear. CONCLUSIONS: The rates of reoperation, implant revision or removal, and common complications after total hip arthroplasty were strongly associated with BMI. PMID- 26842407 TI - Bariatric Orthopaedics: Total Hip Arthroplasty in Super-Obese Patients (Those with a BMI of >=50 kg/m2). AB - BACKGROUND: The purpose of this study was to assess the clinical and patient reported outcomes of primary total hip arthroplasty in super-obese patients (those with a body mass index [BMI] of >=50 kg/m(2)) compared with a matched group of patients who had a normal BMI (<30 kg/m(2)). A secondary objective was to assess patients' experiences in finding a treating surgeon. METHODS: Forty eight hips in forty-five patients who had a minimum BMI of 50 kg/m(2) and who had undergone a primary total hip arthroplasty at one of four high-volume institutions between 2001 and 2010 were reviewed. This included twenty-six women and nineteen men who had a mean age of fifty-four years (range, thirty-six to seventy-one years) and who were followed for a mean time of six years (range, four to twelve years). These patients were compared in a 1:3 ratio with a non obese matched group (those with a BMI of <30 kg/m(2)) of 135 patients who had undergone total hip arthroplasty during the same time period by the same surgeons. The outcomes evaluated included implant survivorship, complication rates, Harris hip scores, 36-item Short-Form (SF)-36 questionnaires, University of California Los Angeles (UCLA) activity scores, and patient experience in finding a treating surgeon. RESULTS: The super-obese group had a 4.5 times higher odds ratio of undergoing a revision when compared with the matching group (p = 0.06); the overall implant survivorship was 89.6% for the super-obese group and 97.8% for the matching group. The super-obese group also had a significantly higher odds ratio (7.7) of complications compared with the matching group (p = 0.017). The super-obese group also had significantly lower mean values for the Harris hip score (82 points for the super-obese group compared with 91 points for the matched group; p = 0.002), the SF-36 Physical Component Summary score (39 points for the super-obese group and 49 points for the matched group; p = 0.001), the SF-36 Mental Component Summary scores (46 points for the super-obese group and 58 points for the matched group; p = 0.001), and the UCLA activity score (3.9 points for the super-obese group compared with 6.2 points for the matched group; p = 0.001). Compared with the matched group, super-obese patients were evaluated by a larger number of orthopaedic surgeons prior to undergoing total hip arthroplasty. CONCLUSIONS: The clinical and patient-reported outcomes of primary total hip arthroplasty were lower in the super-obese patients. These patients also faced challenges in finding surgeons who would perform their procedure. Super-obese patients may benefit from counseling with their treating surgeon to set realistic expectations with regard to the outcomes of their procedure. PMID- 26842408 TI - Are the Symptoms of Calcific Tendinitis Due to Neoinnervation and/or Neovascularization? AB - BACKGROUND: Calcific tendinitis can be a substantial cause of pain and dysfunction in the shoulder, and the pathophysiology is unclear. Recent studies have shown a link among nerve ingrowth, neovascularization, and pain in tendinopathy. The aim of this study was to determine whether there is evidence of neoinnervation and/or neovascularization in calcific tendinitis lesions of the shoulder. METHODS: At arthroscopy, ultrasound was used to identify calcium within the tendon. Samples were taken from the supraspinatus tendon adjacent to the calcific lesion (in the calcific tendinitis group, with ten patients), the torn supraspinatus tendon of patients undergoing rotator cuff repair (the rotator cuff tear group, with ten patients), and the subscapularis tendon of patients undergoing a stabilization surgical procedure (the control group, with ten patients). Biopsied tendon samples were evaluated immunohistochemically by quantifying the presence of macrophages (using CD68 and CD206), T cells (CD3), mast cells (mast cell tryptase), vascular endothelium (CD34), and peripheral nerve markers (PGP 9.5). RESULTS: There was a twofold to eightfold increase of nerve markers, neovascularization, macrophages, M2 macrophages, and mast cells in the calcific tendinitis group compared with the rotator cuff tear group (p < 0.001) and the control group (p < 0.001). Increased nerve counts positively correlated with more frequent extreme pain (r = 0.5, p < 0.01) and with increased neovascularization (r = 0.7, p < 0.01) and counts of CD68 macrophages (r = 0.8, p < 0.01), M2 macrophages (r = 0.6, p < 0.01), and mast cells (r = 0.7, p < 0.01). CONCLUSIONS: This is the first study to show a significant increase in neovascularization and neoinnervation in calcific tendinitis lesions of the shoulder along with an eightfold increase in mast cells and macrophages. The findings are consistent with the hypothesis that, in calcific tendinitis, the calcific material is inducing a vigorous inflammatory response within the tendon with formation of new blood vessels and nerves. CLINICAL RELEVANCE: This study helps to explain why calcific tendinitis is related to substantial pain in the clinical setting. PMID- 26842409 TI - Management and Outcome of Dens Fracture Nonunions in Geriatric Patients. AB - BACKGROUND: Dens fractures are known to have high rates of pseudarthrosis. The aim of this study was to define clinical and radiographic long-term outcomes, specifically in relation to osseous union, cervical spine movement, neurological sequelae, and quality of life, in a geriatric cohort (sixty-five years of age or older) treated operatively or nonoperatively for a dens fracture nonunion. METHODS: Forty-four patients (twenty-eight women and sixteen men; average age, seventy-two years) met the inclusion criteria and were enrolled in this study. Sixteen patients (36%) underwent operative stabilization with posterior cervical arthrodesis, and twenty-eight (64%) were treated nonoperatively with a predefined protocol. All patients had a post-treatment follow-up period of at least five years. RESULTS: Radiographic evaluation showed osseous union at the site of the C1-C2 arthrodesis in all sixteen patients who had undergone surgical treatment. Clinical follow-up revealed that fourteen had satisfactory results following postoperative rehabilitation. In contrast, radiographic evaluation of the twenty eight nonoperatively treated patients showed persistence of the pseudarthrosis of the dens in twenty-six and osseous union of the dens in two. All twenty-eight patients (100%) had a satisfactory clinical outcome. CONCLUSIONS: C1-C2 arthrodesis was a reliable treatment option for dens fracture nonunions that were unstable, those associated with neurological symptoms, and those causing persistent pain. Clinical and radiographic monitoring was an acceptable nonoperative treatment option but was associated with a very low rate of osseous union of the dens. PMID- 26842410 TI - Improved Prognosis for Patients with Ewing Sarcoma in the Sacrum Compared with the Innominate Bones: The Scandinavian Sarcoma Group Experience. AB - BACKGROUND: Treatment of Ewing sarcoma of the pelvic bones remains one of the most difficult tasks in the treatment of bone sarcomas. Whether surgery or radiation therapy is the best local treatment is still a matter of debate. The aim of the present study was to compare sacral and nonsacral sites with regard to the treatment and outcome of pelvic Ewing sarcomas. METHODS: Patients with Ewing sarcoma of the osseous pelvis diagnosed between 1986 and 2011 were identified through the Scandinavian Sarcoma Group registry. Data regarding tumor size, local treatment (surgery or radiation therapy), metastatic disease, surgical margins, local recurrence, and overall survival were analyzed. RESULTS: Of the 117 patients examined, eighty-eight had tumors in the innominate bones and twenty nine, in the sacrum. Radiation therapy was the sole local treatment for 40% of the innominate bone tumors in contrast to 79% of the sacral tumors. The five-year disease-free survival rate in the latter group (66%) was greater than that in the group with tumors in the innominate bones (40%) (p = 0.02 adjusted for size). CONCLUSIONS: Disease-free survival among patients with Ewing sarcoma was improved when the tumor was localized in the sacrum compared with the innominate bones, where these tumors are generally larger. Local radiation therapy alone appears to result in good local tumor control and may be the treatment of choice for sacral tumors. PMID- 26842412 TI - Improving Resident Performance in Knee Arthroscopy: A Prospective Value Assessment of Simulators and Cadaveric Skills Laboratories. AB - BACKGROUND: Cadaveric skills laboratories and virtual reality simulators are two common methods used outside of the operating room to improve residents' performance of knee arthroscopy. We are not aware of any head-to-head comparisons of the educational values of these two methodologies. The purpose of this prospective randomized trial was to assess the efficacy of these training methods, compare their rates of improvement, and provide economic value data to programs seeking to implement such technologies. METHODS: Orthopaedic surgery residents were randomized to one of three groups: control, training on cadavera (cadaver group), and training with use of a simulator (simulator group). Residents completed pretest and posttest diagnostic knee arthroscopies on cadavera that were timed and video-recorded. Between the pretest and posttest, the control group performed no arthroscopy, the cadaver group performed four hours of practice on cadavera, and the simulator group trained for four hours on a simulator. All tests were scored in a blinded, randomized fashion using the validated Arthroscopy Surgical Skill Evaluation Tool (ASSET). The mean improvement in the ASSET score and in the time to complete the procedure were compared between the pretest and posttest and among the groups. RESULTS: Forty five residents (fifteen per group) completed the study. The mean difference in the ASSET score from the pretest to the posttest was -0.40 (p = 0.776) in the control group, +4.27 (p = 0.002) in the cadaver group, and +1.92 (p = 0.096) in the simulator group (p = 0.015 for the comparison among the groups). The mean difference in the test-completion time (minutes:seconds) from the pretest to the posttest was 0:07 (p = 0.902) in the control group, 3:01 (p = 0.002) in the cadaver group, and 0:28 (p = 0.708) in the simulator group (p = 0.044 for the comparison among groups). Residents in the cadaver group improved their performance at a mean of 1.1 ASSET points per hour spent training whereas those in the simulator group improved 0.5 ASSET point per hour of training. CONCLUSIONS: Cadaveric skills laboratories improved residents' performance of knee arthroscopy compared with that of matched controls. Residents practicing on cadaveric specimens improved twice as fast as those utilizing a high-fidelity simulator; however, based on cost estimation specific to our institution, the simulator may be more cost-effective if it is used at least 300 hours per year. Additional study of this possibility is warranted. PMID- 26842411 TI - Bone-Grafting in Polyostotic Fibrous Dysplasia. AB - BACKGROUND: Polyostotic fibrous dysplasia is a skeletal disease that results from somatic activating mutations in the gene GNAS in skeletal stem cells, leading to proliferation of immature osteogenic cells with replacement of normal marrow and bone with fibro-osseous tissue. Lesions may cause bone deformity or fracture. In the surgical care of polyostotic fibrous dysplasia, the role of grafting and the optimal grafting material are not clear. The purpose of this study was to evaluate the long-term survival of bone-grafting procedures in subjects with polyostotic fibrous dysplasia over time. METHODS: The operative reports and radiographs of a cohort of subjects with polyostotic fibrous dysplasia followed in a natural history study were reviewed. Twenty-three subjects (mean age at the time of enrollment, thirteen years [range, two to forty years]) with fifty-two bone-grafting procedures had a mean follow-up time of 19.6 years (range, twenty nine months to forty-seven years). Kaplan-Meier life table estimates, Cox proportional hazard models, and t tests comparing means were performed to assess various aspects of graft survival. RESULTS: Kaplan-Meier curves showed a 50% estimate of survival of 14.5 years. Cox proportional hazards models showed no advantage comparing allograft with autograft or structural with nonstructural graft materials. The mean age of the patients was significantly greater (p < 0.001) in the subgroup of subjects in whom grafts were maintained over time (20.9 years) compared with the subgroup of patients whose grafts were resorbed over time (9.8 years). CONCLUSIONS: Bone-grafting, including both allograft and autograft, is of limited value in ablating the lesions of fibrous dysplasia. The expectations of patients and surgeons should include the high probability of graft resorption over time with return of bone characteristics of fibrous dysplasia, particularly in younger patients. This suggests the maintenance of normal bone mechanics with implant support should be the priority of any surgical intervention. PMID- 26842413 TI - A Patient Follow-up Program for Short-Term Surgical Mission Trips to a Developing Country. AB - BACKGROUND: We describe a follow-up program for patients undergoing surgical procedures with documented results from short-term surgical mission trips to the developing world. The surgical procedures were all performed at a government hospital in Pucallpa, Peru, a remote city in the Amazon. METHODS: Between July 2007 and January 2012, ten surgical mission trips were completed with a mean time of six days on location and a mean number of 2.3 surgeons (range, two to five surgeons) per trip. A Peruvian general surgeon conducted postoperative visits at time intervals of two to four weeks, five to sixteen weeks, four to seven months, and eight to twelve months. Each visit included the completion of a patient outcome form, radiographs, and functional range-of-motion photographs. Patient demographic characteristics; type of surgical procedure; completed follow-up; complications including infection, malunion, or nonunion; and clinical results were analyzed. RESULTS: Of the 127 patients eligible for analysis, twenty-three patients were lost to follow-up, leaving a follow-up rate of 81.9% (104 of 127 patients). Patients were predominantly male (63.5%) and had a mean age of 37.0 years (range, ten months to 93.4 years). The mean length of follow-up was 11.8 months, with a mean number of 3.7 postoperative encounters. Orthopaedic trauma fixation was the predominant surgical procedure (57%), with forty-two procedures (40%) being open reduction and internal fixation. In the 104 patients, successful wound-healing occurred in 101 (97%) and 100 (96%) had a functional outcome deemed to be good or fair by the in-country physician. The infection rate was 2.9% (three patients), with 97% (fifty-seven of fifty-nine) of fractures united. There was one nerve injury in a pediatric patient treated for supracondylar humeral malunion, and two cases of prominent implant necessitating removal. The mean direct cost of the follow-up program was $20,041 in U.S. dollars per year. CONCLUSIONS: It is possible to develop a sustainable surgical patient follow-up program with robust results and to achieve acceptable outcomes for orthopaedic conditions, even in an austere medical environment. PMID- 26842414 TI - Role of Cages in Revision Arthroplasty of the Acetabulum. AB - ? The outcome of acetabular revision is heavily influenced by the degree of associated bone loss.? Uncemented hemispherical acetabular components can be used in the majority of acetabular revisions, although occasionally the degree of bone loss precludes the stability of the hemispherical component at the correct anatomic level or there is minimal bleeding host bone left for biologic fixation.? Massive acetabular bone loss resulting in the need for bone grafts or highly porous augments involving more than half of the acetabulum is one of the main indications for the use of cages.? The cup-cage reconstruction is based on bone-grafting the deficient acetabulum and securing a hemispherical, highly porous metal component with multiple screws to bridge the discontinuity and off loading the hemispherical component with a titanium cage spanning from ischium to ilium.? In addition to managing pelvic discontinuities, the cup-cage construct can also be used in hips without discontinuity as the hemispherical, highly porous metal component is used to restore bone stock.? In situations in which there is not enough bleeding host bone to secure a hemispherical component, a highly porous metal augment can be used to address the osseous deficiency. The augment is also protected with a cage to assist bone ingrowth. PMID- 26842415 TI - What to Read and How to Read It: A Guide for Orthopaedic Surgeons. PMID- 26842416 TI - Is BMI an Independent Risk Factor for Unfavorable Outcomes Following Total Hip Arthroplasty? Commentary on an article by Eric R. Wagner, MD, et al.: "Effect of Body Mass Index on Complications and Reoperations After Total Hip Arthroplasty". PMID- 26842417 TI - What Will We Do Now with the Super-Obese Patient Undergoing Total Hip Arthroplasty? Commentary on an article by Kimona Issa, MD, et al.: "Bariatric Orthopaedics: Total Hip Arthroplasty in Super-Obese Patients (Those with a BMI of >=50 kg/m2)". PMID- 26842418 TI - Why Do Tendons Hurt? Lessons from the Study of Calcific Tendinitis: Commentary on an article by Lisa Hackett, AMS, et al.: "Are the Symptoms of Calcific Tendinitis Due to Neoinnervation and/or Neovascularization?". PMID- 26842419 TI - Facile and Chemically Pure Preparation of YVO4:Eu(3+) Colloid with Novel Nanostructure via Laser Ablation in Water. AB - A YVO4:Eu(3+) colloid with an interesting nanostructure was formed by pulsed laser ablation in deionized water without any additives or surfactants. Analyses of particle morphology, composition and optical properties were accomplished by SEM, TEM, EDS PL and UV-vis. Ovoid-like particles formed by the agglomeration of numerous nanocrystals were observed by SEM and TEM, while EDS with area-mode analysis revealed that the content of dopant ion was well retained within the nanoparticles. In addition, the formation mechanism is deduced and discussed for the first time in this research. The findings of this study could provide new insights into the understanding of laser-induced oxide materials and offer an opportunity for other research groups to pursue red emitting nanophosphors with outstandingly purity. PMID- 26842420 TI - Improving human skeletal muscle myosin heavy chain fiber typing efficiency. AB - Single muscle fiber sodium dodecyl sulfate polyacrylamide gel-electrophoresis (SDS-PAGE) is a sensitive technique for determining skeletal muscle myosin heavy chain (MHC) composition of human biopsy samples. However, the number of fibers suitable to represent fiber type distribution via this method is undefined. Muscle biopsies were obtained from the vastus lateralis (VL) of nine resistance trained males (25 +/- 1 year, height = 179 +/- 5 cm, mass = 82 +/- 8 kg). Single fiber MHC composition was determined via SDS-PAGE. VL fiber type distribution [percent MHC I, I/IIa, IIa, IIa/IIx, and total "hybrids" (i.e. I/IIa + IIa/IIx)] was evaluated according to number of fibers analyzed per person (25 vs. 125). VL fiber type distribution did not differ according to number of fibers analyzed (P > 0.05). VL biopsy fiber type distribution of nine subjects is represented by analyzing 25 fibers per person. These data may help minimize cost, personnel time, and materials associated with this technique, thereby improving fiber typing efficiency in humans. PMID- 26842421 TI - The Effects of Female Sex Hormones on Ventricular Premature Beats and Repolarization Parameters in Physiological Menstrual Cycle. AB - BACKGROUND: The effects of gender difference on cardiac electrophysiology have been well studied. In this study, we aimed to evaluate the effects of estradiol and progesteron changes occuring in physiological menstrual cycle on ventricular premature beats (VPBs) and cardiac repolarization parameters. METHODS: Women of reproductive age with VPBs were included into the study group and healthy women were recruited as the control group. During the menstruation period, a 12-lead electrocardiography, blood samples, and 24-hour rhythm Holter were applied to the study group. Similarly, all tests were repeated in the estimated ovulation period (12-14 days before menstruation) by all cases. RESULTS: The study group consisted of 20 women patients with VPB, and the control group of 18 healthy women. While the number of VPB in the menstruation period was 210 beats/day (interquartile range [IQR]: 1,144), it decreased to 86 beats/day (IQR: 251) in the ovulation period with statistical significance (P < 0.05). Average heart rate in the menstruation period was 81.4 +/- 10 beats/min and it significantly increased to 84.6 +/- 8 beats/min in the ovulation period (P < 0.05). There were no differences in cardiac repolarization parameters in both menstruation and ovulation periods between the study and control groups. Comparing the menstruation and the ovulation periods, J-Tpeak interval, which reflects early repolarization, was shorter in the ovulation period (193 +/- 27.7 ms and 201.1 +/ 28.6 ms, respectively; P < 0.05). Other repolarization parameters did not show any significant difference. CONCLUSION: VPB frequency decreases with estradiol peak in the ovulation period. This suggests that estrogen may have protective effects against ventricular arrhythmias. PMID- 26842424 TI - Total synthesis of laidlomycin. AB - The synthesis of laidlomycin is described. With an established stereocontrolled synthetic route to the aldehyde 5, the known beta-keto phosphonate 4 was coupled with 5 and the resulting enone was subjected to a sequential hydrogenolysis/hydrogenation and equilibration process to effect the correct spiroketalization for the natural product. The stereogenic carbons were elaborated by desymmetrization for C12, allylation for C13, vanadyl-induced epoxidation for C16, Zn(BH4)2 reduction for C17, a chiral building block for C18 and C24, Shi epoxidation for C20 and C21, Myers' alkylation for C22, and thermodynamic control for C25. PMID- 26842423 TI - The Prevalence of Atherosclerosis in Those with Inflammatory Connective Tissue Disease by Race, Age, and Traditional Risk Factors. AB - Systemic inflammation promotes cardiovascular disease. Inflammatory connective tissue diseases (CTD) like lupus and rheumatoid arthritis associate with cardiovascular risk, but it is unknown whether particular groups of patients have enhanced propensity for atherosclerotic cardiovascular disease (ASCVD) associated with their CTD. Analysis of aggregate health record data at a large U.S. academic center identified CTD and ASCVD status for 287,467 African American and white adults. ASCVD prevalence in those with CTD was 29.7% for African Americans and 14.7% for white patients with prevalence ratios, compared to those without CTD, of 3.1 and 1.8, respectively. When different types of CTD were analyzed individually (rheumatoid arthritis; lupus; scleroderma; Sjogren Syndrome; dermatomyositis/polymyositis; unspecified/mixed CTD; other inflammatory arthropathy), increased ASCVD rates were found in nearly all subsets, always with higher prevalence ratios in African Americans. The prevalence ratio of ASCVD was particularly high in young African Americans. Furthermore, individuals lacking traditional cardiovascular risk factors had more ASCVD if they had CTD (prevalence ratio 2.9). Multivariate analysis confirmed a positive interaction between CTD and African-American race and a negative interaction between CTD and age. The factors driving the observed disproportionate CTD-associated ASCVD in African Americans, young adults, and those without traditional risk factors warrant further study. PMID- 26842422 TI - tDCS for the treatment of depression: a comprehensive review. AB - Transcranial direct current stimulation (tDCS) has been investigated for the treatment of major depressive disorders in recent years. Here, we review the implications of current research for the clinical use of tDCS in the treatment of major depressive disorder. Meta-analyses, randomized, placebo-controlled clinical trials, open-label trials, case reports and review articles were identified through a systematic search of the literature database of the National Institutes of Health (USA). Available articles were evaluated with regard to their clinical relevance. Results of tDCS efficacy are inconsistent due to the small sample sizes, the heterogeneous patient samples and the partially high treatment resistance in some studies. Overall, tDCS has very low side effects. Meta analyses suggest some efficacy of tDCS in the treatment of acute depressive disorder with moderate effect size, and low efficacy in treatment-resistant depression. A general statement about the efficacy of tDCS as a therapeutic tool in major depression seems to be premature. tDCS is considered as a safe therapeutic option and is associated with only minor side effects. The effectiveness of tDCS decreases with resistance to treatment. Psychotropic drugs may attenuate or amplify its effects. The use of 2 mA current strength over 20 min per day over a short time span can be considered as safe. PMID- 26842426 TI - The influence of oxidation debris containing in graphene oxide on the adsorption and electrochemical properties of 1,10-phenanthroline-5,6-dione. AB - It is gradually accepted that graphene oxide, which is derived from the exfoliation of graphite oxide that is synthesized by the chemical oxidation of graphite, actually consists of partially oxidized graphene sheets and highly oxidized carbonaceous debris. The quantity of oxidation debris comprises around one third of the total mass of the graphene oxide. The presence of oxidation debris has a significant impact on the physical and chemical properties of graphene oxide. In this article, we address the influence of the oxidation debris on the surface properties of graphene oxide. We discovered that the surface adsorption of organic molecules on graphene oxide was improved greatly after the elimination of the oxidation debris. A typical redox mediator, 1,10 phenanthroline-5,6-dione, was studied as the model adsorbed molecule in terms of its adsorption quantity and electrochemical response. After removing the oxidation debris, a five-fold increase in adsorption capacity is achieved on the same amount of graphene oxide. Correspondingly, the electrochemical response for the oxidation of NADH mediated by the adsorbed 1,10-phenanthroline-5,6-dione was enhanced as well, which led to improved analytical performances in terms of the sensitivity, linear range and detection limit for the purified graphene oxide modified electrode. PMID- 26842428 TI - Selective silicate-directed motility in diatoms. AB - Diatoms are highly abundant unicellular algae that often dominate pelagic as well as benthic primary production in the oceans and inland waters. Being strictly dependent on silica to build their biomineralized cell walls, marine diatoms precipitate 240 * 10(12) mol Si per year, which makes them the major sink in the global Si cycle. Dissolved silicic acid (dSi) availability frequently limits diatom productivity and influences species composition of communities. We show that benthic diatoms selectively perceive and behaviourally react to gradients of dSi. Cell speed increases under dSi-limited conditions in a chemokinetic response and, if gradients of this resource are present, increased directionality of cell movement promotes chemotaxis. The ability to exploit local and short-lived dSi hotspots using a specific search behaviour likely contributes to micro-scale patch dynamics in biofilm communities. On a global scale this behaviour might affect sediment-water dSi fluxes and biogeochemical cycling. PMID- 26842427 TI - Echium oil increased the expression of a Delta4 Fads2 fatty acyl desaturase and the deposition of n-3 long-chain polyunsaturated fatty acid in comparison with linseed oil in striped snakehead (Channa striata) muscle. AB - Despite the potential of vegetable oils as aquafeed ingredients, a major drawback associated with their utilization is the inferior level of beneficial n-3 long chain polyunsaturated fatty acids (LC-PUFA). Echium oil (EO), which is rich in stearidonic acid (SDA, 18:4n-3), could potentially improve the deposition of n-3 LC-PUFA as the biosynthesis of LC-PUFA is enhanced through bypassing the rate limiting ?6 desaturation step. We report for the first time an attempt to investigate whether the presence of a desaturase (Fads2) capable of ?4 desaturation activities and an elongase (Elovl5) will leverage the provision of dietary SDA to produce a higher rate of LC-PUFA bioconversion. Experimental diets were designed containing fish oil (FO), EO or linseed oil (LO) (100FO, 100EO, 100LO), and diets which comprised equal mixtures of the designated oils (50EOFO and 50EOLO) were evaluated in a 12-week feeding trial involving striped snakeheads (Channa striata). There was no significant difference in growth and feed conversion efficiency. The hepatic fatty acid composition and higher expression of fads2 and elovl5 genes in fish fed EO-based diets indicate the utilization of dietary SDA for LC-PUFA biosynthesis. Collectively, this resulted in a higher deposition of muscle eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) compared to LO-based diets. Dietary EO improved the ratio of n-3 LC-PUFA to n-6 LC-PUFA in fish muscle, which is desirable for human populations with excessive consumption of n-6 PUFA. This study validates the contribution of SDA in improving the content of n-3 LC-PUFA and the ratio of EPA to arachidonic acid (ARA, 20:4n-6) in a freshwater carnivorous species. PMID- 26842429 TI - A practical divergence measure for survival distributions that can be estimated from Kaplan-Meier curves. AB - This paper introduces a new simple divergence measure between two survival distributions. For two groups of patients, the divergence measure between their associated survival distributions is based on the integral of the absolute difference in probabilities that a patient from one group dies at time t and a patient from the other group survives beyond time t and vice versa. In the case of non-crossing hazard functions, the divergence measure is closely linked to the Harrell concordance index, C, the Mann-Whitney test statistic and the area under a receiver operating characteristic curve. The measure can be used in a dynamic way where the divergence between two survival distributions from time zero up to time t is calculated enabling real-time monitoring of treatment differences. The divergence can be found for theoretical survival distributions or can be estimated non-parametrically from survival data using Kaplan-Meier estimates of the survivor functions. The estimator of the divergence is shown to be generally unbiased and approximately normally distributed. For the case of proportional hazards, the constituent parts of the divergence measure can be used to assess the proportional hazards assumption. The use of the divergence measure is illustrated on the survival of pancreatic cancer patients. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26842425 TI - Effect of structured physical activity on prevention of serious fall injuries in adults aged 70-89: randomized clinical trial (LIFE Study). AB - OBJECTIVE: To test whether a long term, structured physical activity program compared with a health education program reduces the risk of serious fall injuries among sedentary older people with functional limitations. DESIGN: Multicenter, single blinded randomized trial (Lifestyle Interventions and Independence for Elders (LIFE) study). SETTING: Eight centers across the United States, February 2010 to December 2011. PARTICIPANTS: 1635 sedentary adults aged 70-89 years with functional limitations, defined as a short physical performance battery score <= 9, but who were able to walk 400 m. INTERVENTIONS: A permuted block algorithm stratified by field center and sex was used to allocate interventions. Participants were randomized to a structured, moderate intensity physical activity program (n=818) conducted in a center (twice a week) and at home (3-4 times a week) that included aerobic, strength, flexibility, and balance training activities, or to a health education program (n=817) consisting of workshops on topics relevant to older people and upper extremity stretching exercises. MAIN OUTCOME MEASURES: Serious fall injuries, defined as a fall that resulted in a clinical, non-vertebral fracture or that led to a hospital admission for another serious injury, was a prespecified secondary outcome in the LIFE Study. Outcomes were assessed every six months for up to 42 months by staff masked to intervention assignment. All participants were included in the analysis. RESULTS: Over a median follow-up of 2.6 years, a serious fall injury was experienced by 75 (9.2%) participants in the physical activity group and 84 (10.3%) in the health education group (hazard ratio 0.90, 95% confidence interval 0.66 to 1.23; P=0.52). These results were consistent across several subgroups, including sex. However, in analyses that were not prespecified, sex specific differences were observed for rates of all serious fall injuries (rate ratio 0.54, 95% confidence interval 0.31 to 0.95 in men; 1.07, 0.75 to 1.53 in women; P=0.043 for interaction), fall related fractures (0.47, 0.25 to 0.86 in men; 1.12, 0.77 to 1.64 in women; P=0.017 for interaction), and fall related hospital admissions (0.41, 0.19 to 0.89 in men; 1.10, 0.65 to 1.88 in women; P=0.039 for interaction). CONCLUSIONS: In this trial, which was underpowered to detect small, but possibly important reductions in serious fall injuries, a structured physical activity program compared with a health education program did not reduce the risk of serious fall injuries among sedentary older people with functional limitations. These null results were accompanied by suggestive evidence that the physical activity program may reduce the rate of fall related fractures and hospital admissions in men.Trial registration ClinicalsTrials.gov NCT01072500. PMID- 26842432 TI - Healthy migration needs a long-term plan. PMID- 26842430 TI - Accounting for the influence of inflammation on retinol-binding protein in a population survey of Liberian preschool-age children. AB - Vitamin A deficiency (VAD) is an important contributor to child morbidity and mortality. The prevalence of VAD, measured by retinol-binding protein (RBP) or retinol, is overestimated in populations with a high prevalence of inflammation. We aimed to quantify and adjust for the effect of inflammation on VAD prevalence in a nationally representative survey of Liberian children 6 to 35 months of age. We compared five approaches to adjust RBP for inflammation and estimate VAD prevalence (defined as RBP < 0.7 umol/L): (1) ignoring inflammation; (2) excluding individuals with inflammation (C-reactive protein (CRP) >5 mg/L or alpha1-acid glycoprotein (AGP) >1 g/)L; (3) multiplying each individual's RBP by an internal correction factor; (4) by an external correction factor; and (5) using regression (corrected RBP = exp(InRBP - beta1 (lnCRPobs -lnCRPref ) - beta2 (lnAGPobs -lnAGPref )). Corrected RBP was based on a regression model where reference lnCRP and lnAGP were set to the maximum of the lowest decile. The unadjusted prevalence of VAD was 24.7%. Children with elevated CRP and/or AGP had significantly lower RBP concentrations than their apparently healthy peers (geometric mean RBP 0.79 umol/L (95% CI: 0.76, 0.82) vs. 0.95 umol/L (95% CI: 0.92, 0.97), P < 0.001). Using approaches 2-5 resulted in a prevalence of VAD of 11.6%, 14.3%, 13.5% and 7.3%, respectively. Depending on the approach, the VAD prevalence is reduced 10-17 percentage points when inflammation is taken into account. Further quantification of the influence of inflammation on biomarkers of vitamin A status from other national surveys is needed to compare and recommend the preferred adjustment approach across populations. PMID- 26842431 TI - Reconciling city and country: China's lessons for a divided world. PMID- 26842433 TI - Promising the moon. PMID- 26842434 TI - Refugees: towards better access to health-care services. PMID- 26842435 TI - The future leadership of WHO. PMID- 26842439 TI - France investigates drug trial disaster. PMID- 26842436 TI - Empowering young leaders for social justice in health. PMID- 26842440 TI - Cuba's focus on preventive medicine pays off. PMID- 26842441 TI - The judgment dilemma. PMID- 26842443 TI - Making people care. PMID- 26842444 TI - Eltrombopag for chronic immune thrombocytopenia - Authors' reply. PMID- 26842445 TI - Eltrombopag for chronic immune thrombocytopenia. PMID- 26842446 TI - Effectiveness of an internet-delivered handwashing intervention. PMID- 26842447 TI - Effectiveness of an internet-delivered handwashing intervention. PMID- 26842448 TI - Effectiveness of an internet-delivered handwashing intervention - Author's reply. PMID- 26842449 TI - Tobacco control: a victim of political instability in Greece. PMID- 26842451 TI - Department of Error. PMID- 26842452 TI - Department of Error. PMID- 26842450 TI - Tracheobronchial transplantation. PMID- 26842453 TI - Department of Error. PMID- 26842454 TI - Department of Error. PMID- 26842455 TI - The future of medicine: a students' perspective. PMID- 26842456 TI - Cost of protection against pandemics is small. PMID- 26842458 TI - Zebrafish olfactory receptor ORA1 recognizes a putative reproductive pheromone. AB - Teleost v1r-related ora genes constitute a small and highly conserved olfactory receptor gene family, and their direct orthologs are present in lineages as distant as cartilaginous fishes. Recently, the first member of the ora gene family was deorphanized. ORA1 detects p-hydroxyphenylacetic acid with high sensitivity and specificity. This compound elicits olfactory-mediated oviposition behavior in adult zebrafish mating pairs, suggesting a potential function as a reproductive pheromone for pHPAA itself or a related substance. This association of an odor and its cognate receptor with an oviposition response may provide a molecular basis for studying neural circuits involved in fish reproduction. PMID- 26842460 TI - Catalytically solid-phase self-organization of nanoporous SnS with optical depolarizability. AB - The catalytic solid-phase synthesis of self-organized nanoporous tin sulfide (SnS) with enhanced absorption, manipulative transmittance and depolarization features is demonstrated. Using an ultralow radio-frequency (RF) sputtering power, the variation of the orientation angle between the anodized aluminum oxide (AAO) membrane and the axis of the sputtered ion beam detunes the catalytically synthesized SnS from nanorod to nanoporous morphology, along the sidewall of the AAO membrane. The ultraslow catalytic sputtering synthesis on the AAO at the RF plasma power of 20 W and the orientation angle of 0 degrees regulates the porosity and integrality of nanoporous SnS, with average pore diameter of 80-150 nm. When transferring from planar to nanoporous structure, the phase composition changes from SnS to SnS2-Sn2S3, and the optical bandgap shrinks from 1.43 to 1.16 eV, due to the preferred crystalline orientation, which also contributes to an ultralow reflectance of <1% at 200-500 nm when both the transmittance and the surface scattering remain at their maxima. The absorption coefficient is enhanced by nearly one order of magnitude with its minimum of >5 * 10(4) cm(-1) at the wavelength between 200 and 700 nm, due to the red-shifting of the absorption spectrum to at least 100 nm. The catalytically self-organized nanoporous SnS causes strong haze and beam divergence of 20 degrees -30 degrees by depolarized nonlinear scattering at the surface, which favors the solar energy conversion with reduced surface reflection and enhanced photon scattering under preserved transmittance. PMID- 26842461 TI - Do patients with lung cancer recall physician-initiated discussions about planning for end-of-life care following disclosure of a terminal prognosis? AB - BACKGROUND: Communicating with patients about their prognosis and goals of care, including offering opportunities to engage in advance care planning (ACP) is widely recognised as best practice. Little is known about terminally ill patients' perceptions of communication and ACP practice following disclosure of their terminal prognosis. OBJECTIVES: To examine whether terminally ill patients with lung cancer and their relatives recall conversations with disclosing physicians, about their concerns, goals of care or any offers to engage in ACP. METHODS: Qualitative study using semistructured interviews with patients and their family members. The study setting was a cancer centre and cancer unit in northern England. RESULTS: 25 patients with advanced lung cancer (18 men and 7 women, aged 47-85) and 19 family members, mainly from lower social economic classes, took part in the study. Participants had little or no recall of physicians initiating discussions about their concerns, or goals of care and did not perceive that they had been provided with either information about or opportunities to engage in ACP. Some participants reported a sense of abandonment following the disclosure of a terminal prognosis. This sense was compounded by a range of difficult emotional experiences following the disclosure. CONCLUSIONS: It may be inappropriate to initiate discussions about end-of-life care planning immediately following the disclosure of a terminal prognosis. To avoid patients feeling abandoned physicians need to consider how they or another appropriate person can provide information and opportunities for terminally ill patients to engage in a process of ACP. TRIAL REGISTRATION NUMBER: 06/Q2307/22. PMID- 26842459 TI - High resolution Physio-chemical Tissue Analysis: Towards Non-invasive In Vivo Biopsy. AB - Conventional gold standard histopathologic diagnosis requires information of both high resolution structural and chemical changes in tissue. Providing optical information at ultrasonic resolution, photoacoustic (PA) technique could provide highly sensitive and highly accurate tissue characterization noninvasively in the authentic in vivo environment, offering a replacement for histopathology. A two dimensional (2D) physio-chemical spectrogram (PCS) combining micrometer to centimeter morphology and chemical composition simultaneously can be generated for each biological sample with PA measurements at multiple optical wavelengths. This spectrogram presents a unique 2D "physio-chemical signature" for any specific type of tissue. Comprehensive analysis of PCS, termed PA physio-chemical analysis (PAPCA), can lead to very rich diagnostic information, including the contents of all relevant molecular and chemical components along with their corresponding histological microfeatures, comparable to those accessible by conventional histology. PAPCA could contribute to the diagnosis of many diseases involving diffusive patterns such as fatty liver. PMID- 26842462 TI - Epidemiology of diabetic ketoacidosis in Arab patients with type 1 diabetes: a systematic review. AB - AIMS: Diabetic ketoacidosis (DKA) is an acute and risky complication of type 1 diabetes. The aim of this study is to build the overall rate of DKA in Arab patients with type 1 diabetes in the 22 Arab nations. This is expected to tailor the healthcare approaches in Arab countries where attention is needed to save lives from the devastating consequences of DKA. METHODS: The study here is a quantitative analysis of the articles indexed in four different scientific literature databases: Web of Science, PubMed, Science Direct and Scopus, from inception to June 2015. Arab patients with type 1 diabetes who presented with DKA have been captured. Key information was possible to extract for patients belong to only 12 Arab countries out of the 22 Arab patients. RESULTS: Twenty-nine studies in 12 different Arab countries captured 4,688 type 1 diabetes patients with overall rates of 46.7% patients presented with DKA, ranging from a low of 17% in Egypt to a high of 100% in Morocco, Algeria and Tunisia. CONCLUSION: This is the first descriptive quantitative study to determine the overall DKA rate in 46 years of studies in the Arab world of patients with type 1 diabetes; DKA rates were found to range from 17% to 100% with overall rate of 46.7%. PMID- 26842457 TI - Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naive HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. AB - OBJECTIVES: Lamivudine (3TC) and emtricitabine (FTC) are considered interchangeable in recommended tenofovir disoproxil-fumarate (TDF)-containing combination antiretroviral therapies (cARTs). This statement of equivalence has not been systematically studied. We compared the treatment responses to 3TC and FTC combined with TDF in boosted protease inhibitor (PI)-based cART for HIV-1 infected patients. METHODS: An observational study in the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort was carried out between 2002 and 2013. Virological failure rates, time to HIV RNA suppression < 400 copies/mL, and time to treatment failure were analysed using multivariable logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score adjusted models. RESULTS: A total of 1582 ART-naive HIV-1-infected patients initiated 3TC or FTC with TDF and ritonavir-boosted darunavir (29.6%), atazanavir (41.5%), lopinavir (27.1%) or another PI (1.8%). Week 48 virological failure rates on 3TC and FTC were comparable (8.9% and 5.6%, respectively; P = 0.208). The multivariable adjusted odds ratio of virological failure when using 3TC instead of FTC with TDF in PI-based cART was 0.75 [95% confidence interval (CI) 0.32-1.79; P = 0.51]. Propensity score-adjusted models showed comparable results. The adjusted hazard ratio (HR) for treatment failure of 3TC compared with FTC was 1.15 (95% CI 0.58-2.27) within 240 weeks after cART initiation. The time to two consecutive HIV RNA measurements < 400 copies/mL within 48 weeks (HR 0.94; 95% CI 0.78-1.16) and the time to treatment failure after suppression < 400 copies/mL (HR 0.94; 95% CI 0.36-2.50) were not significantly influenced by the use of 3TC in TDF/PI-containing cART. CONCLUSIONS: The virological responses were not significantly different in treatment-naive HIV-1-infected patients starting either 3TC/TDF or FTC/TDF and a ritonavir-boosted PI. PMID- 26842463 TI - The Nuclear Ribonucleoprotein SmD1 Interplays with Splicing, RNA Quality Control, and Posttranscriptional Gene Silencing in Arabidopsis. AB - RNA quality control (RQC) eliminates aberrant RNAs based on their atypical structure, whereas posttranscriptional gene silencing (PTGS) eliminates both aberrant and functional RNAs through the sequence-specific action of short interfering RNAs (siRNAs). The Arabidopsis thaliana mutant smd1b was identified in a genetic screen for PTGS deficiency, revealing the involvement of SmD1, a component of the Smith (Sm) complex, in PTGS. The smd1a and smd1b single mutants are viable, but the smd1a smd1b double mutant is embryo-lethal, indicating that SmD1 function is essential. SmD1b resides in nucleoli and nucleoplasmic speckles, colocalizing with the splicing-related factor SR34. Consistent with this, the smd1b mutant exhibits intron retention at certain endogenous mRNAs. SmD1 binds to RNAs transcribed from silenced transgenes but not nonsilenced ones, indicating a direct role in PTGS. Yet, mutations in the RQC factors UPFRAMESHIFT3, EXORIBONUCLEASE2 (XRN2), XRN3, and XRN4 restore PTGS in smd1b, indicating that SmD1 is not essential for but rather facilitates PTGS. Moreover, the smd1b mtr4 double mutant is embryo-lethal, suggesting that SmD1 is essential for mRNA TRANSPORT REGULATOR4-dependent RQC. These results indicate that SmD1 interplays with splicing, RQC, and PTGS. We propose that SmD1 facilitates PTGS by protecting transgene-derived aberrant RNAs from degradation by RQC in the nucleus, allowing sufficient amounts to enter cytoplasmic siRNA bodies to activate PTGS. PMID- 26842465 TI - Multiple Sclerosis Questionnaire for Job Difficulties (MSQ-Job): definition of the cut-off score. AB - Multiple Sclerosis (MS) mainly affects people of working age. The Multiple Sclerosis Questionnaire for Job Difficulties (MSQ-Job) was designed to measure difficulties in work-related tasks. Our aim is to define cut-off score of MSQ-Job to identify potential critical situations that might require specific attention. A sample of patients with MS completed the MSQ-Job, WHODAS 2.0 and MSQOL-54 respectively for work difficulties, disability and health-related quality of life (HRQoL) evaluation. K-means Cluster Analysis was used to divide the sample in three groups on the basis of HRQoL and disability. ANOVA test was performed to compare the response pattern between these groups. The cut-off score was defined using the receiver operating characteristic (ROC) curve analyses for MSQ-Job total and count of MSQ-Job items scores >=3: a score value corresponding to the maximum of the sensitivity-to-specificity ratio was chosen as the cut-off. Out of 180 patients enrolled, twenty were clustered in the higher severity group. The area under the ROC curve was 0.845 for the MSQ-Job total and 0.859 for the count of MSQ-Job items scores >=3 while the cut-off score was 15.8 for MSQ-Job total and 8 for count of items scored >=3. We recommend the use of MSQ-Job with this calculation as cut-off for identifying critical situations, e.g. in vocational rehabilitation services, where work-related difficulties have a significant impact in terms of lower quality of life and higher disability. PMID- 26842466 TI - Incremental prognostic value of global longitudinal strain in patients with type 2 diabetes mellitus. AB - BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are at high risk for cardiovascular events. The aim of the study was to assess whether global longitudinal strain (GLS) provides prognostic value in these patients. METHODS: A total of 247 T2DM patients without history of cardiovascular complications and participated in the CDATS study were prospectively enrolled. Left ventricular (LV) systolic function was assessed by LV ejection fraction and speckle tracking derived LV systolic GLS. Diastolic function was assessed by E/E' ratio defined as the passive trans-mitral LV inflow velocity to tissue Doppler imaging velocity of the medial mitral annulus. Cardiovascular event included acute coronary syndrome, cerebrovascular stroke, hospitalization for heart failure and cardiovascular death. RESULTS: A total of 18 cardiovascular events occurred during a median follow-up duration of 33 months. Both E/E' ratio [hazard ratio (HR) 1.15, P < 0.01] and GLS (HR 1.39, P < 0.01) were independently associated with cardiovascular events. Importantly, GLS provided incremental prognostic information in addition to clinical data, HbA1c and E/E' ratio (Chi square 77.46, P = 0.04). Receiver-operator characteristic curve analysis demonstrated that E/E' ratio [area under curve (AUC) 0.66, P = 0.03] and GLS (AUC 0.72, P < 0.01) were strong predictors of cardiovascular events. Kaplan-Meier analysis showed that patients with E/E' > 13.6 or GLS > -17.9 % were associated with cardiovascular events. The presence of either a high E/E' ratio or an impaired GLS provides an excellent negative predictive value of cardiovascular events in these patients. CONCLUSIONS: In T2DM patients with no history of cardiovascular disease, impaired GLS was associated with cardiovascular events and provided incremental prognostic value. PMID- 26842464 TI - Time-Series Transcriptomics Reveals That AGAMOUS-LIKE22 Affects Primary Metabolism and Developmental Processes in Drought-Stressed Arabidopsis. AB - In Arabidopsis thaliana, changes in metabolism and gene expression drive increased drought tolerance and initiate diverse drought avoidance and escape responses. To address regulatory processes that link these responses, we set out to identify genes that govern early responses to drought. To do this, a high resolution time series transcriptomics data set was produced, coupled with detailed physiological and metabolic analyses of plants subjected to a slow transition from well-watered to drought conditions. A total of 1815 drought responsive differentially expressed genes were identified. The early changes in gene expression coincided with a drop in carbon assimilation, and only in the late stages with an increase in foliar abscisic acid content. To identify gene regulatory networks (GRNs) mediating the transition between the early and late stages of drought, we used Bayesian network modeling of differentially expressed transcription factor (TF) genes. This approach identified AGAMOUS-LIKE22 (AGL22), as key hub gene in a TF GRN. It has previously been shown that AGL22 is involved in the transition from vegetative state to flowering but here we show that AGL22 expression influences steady state photosynthetic rates and lifetime water use. This suggests that AGL22 uniquely regulates a transcriptional network during drought stress, linking changes in primary metabolism and the initiation of stress responses. PMID- 26842467 TI - Host Protein Moloney Leukemia Virus 10 (MOV10) Acts as a Restriction Factor of Influenza A Virus by Inhibiting the Nuclear Import of the Viral Nucleoprotein. AB - The viral ribonucleoprotein (vRNP) complex of influenza A viruses (IAVs) contains an RNA-dependent RNA polymerase complex (RdRp) and nucleoprotein (NP) and is the functional unit for viral RNA transcription and replication. The vRNP complex is an important determinant of virus pathogenicity and host adaptation, implying that its function can be affected by host factors. In our study, we identified host protein Moloney leukemia virus 10 (MOV10) as an inhibitor of IAV replication, since depletion of MOV10 resulted in a significant increase in virus yield. MOV10 inhibited the polymerase activity in a minigenome system through RNA mediated interaction with the NP subunit of vRNP complex. Importantly, we found that the interaction between MOV10 and NP prevented the binding of NP to importin alpha, resulting in the retention of NP in the cytoplasm. Both the binding of MOV10 to NP and its inhibitory effect on polymerase activity were independent of its helicase activity. These results suggest that MOV10 acts as an anti-influenza virus factor through specifically inhibiting the nuclear transportation of NP and subsequently inhibiting the function of the vRNP complex. IMPORTANCE: The interaction between the influenza virus vRNP complex and host factors is a major determinant of viral tropism and pathogenicity. Our study identified MOV10 as a novel host restriction factor for the influenza virus life cycle since it inhibited the viral growth rate. Conversely, importin-alpha has been shown as a determinant for influenza tropism and a positive regulator for viral polymerase activity in mammalian cells but not in avian cells. MOV10 disrupted the interaction between NP and importin-alpha, suggesting that MOV10 could also be an important host factor for influenza virus transmission and pathogenicity. Importantly, as an interferon (IFN)-inducible protein, MOV10 exerted a novel mechanism for IFNs to inhibit the replication of influenza viruses. Furthermore, our study potentially provides a new drug design strategy, the use of molecules that mimic the antiviral mechanism of MOV10. PMID- 26842469 TI - Replication of Human Herpesviruses Is Associated with Higher HIV DNA Levels during Antiretroviral Therapy Started at Early Phases of HIV Infection. AB - Asymptomatic replication of human herpesviruses (HHV) is frequent in HIV-infected men and is associated with increased T-cell activation and HIV disease progression. We hypothesized that the presence of replication of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) (the most frequently detected HHV) might influence HIV DNA decay during antiretroviral therapy (ART). We investigated 607 peripheral blood mononuclear cell (PBMC) samples from 107 CMV-seropositive, HIV infected men who have sex with men, who started ART within a median of 3 months from their estimated date of infection (EDI) and were monitored for a median of 19 months thereafter. Levels of HIV, CMV, and EBV DNA and cellular HIV RNA were measured by droplet digital PCR (ddPCR) for each time point. Using a general linear mixed-effect regression model, we evaluated associations between the presence of detectable CMV DNA and EBV DNA levels and HIV DNA decay and cellular HIV RNA levels, while adjusting for peak HIV RNA, nadir CD4(+)count, CD4/CD8 ratio, CMV IgG levels, time from EDI to ART initiation, time from ART initiation to virologic suppression, detectable CMV DNA pre-ART, and age. The presence of intermittent CMV DNA in PBMC during ART was significantly associated with slower decay of HIV DNA (P= 0.011) but not with increased cellular HIV RNA transcription or more detectable 2-long terminal repeat circles. Higher levels of EBV DNA were also associated with higher levels of HIV DNA (P< 0.001) and increased unspliced cellular HIV RNA transcription (P= 0.010). These observations suggest that replication of HHV may help maintain a larger HIV DNA reservoir, but the underlying mechanisms remain unclear. IMPORTANCE: Over three-fourths of HIV infected men have at least one actively replicating human herpesvirus (HHV) in their mucosal secretions at any one time. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are the most common, and although it is often asymptomatic, such CMV and EBV replication is associated with higher levels of immune activation and HIV disease progression. We hypothesized that HHV-associated activation of HIV infected CD4(+)T cells might lead to increased HIV DNA. This study found that detectable CMV in blood cells of HIV-infected men was associated with slower decay of HIV DNA even during antiretroviral therapy (ART) that was started during early HIV infection. Similarly, levels of EBV DNA were associated with higher levels of HIV DNA during ART. If this observation points to a causal pathway, interventions that control CMV and EBV replication may be able to reduce the HIV reservoir, which might be relevant to current HIV cure efforts. PMID- 26842468 TI - The Herpes Simplex Virus Latency-Associated Transcript Gene Is Associated with a Broader Repertoire of Virus-Specific Exhausted CD8+ T Cells Retained within the Trigeminal Ganglia of Latently Infected HLA Transgenic Rabbits. AB - Persistent pathogens, such as herpes simplex virus 1 (HSV-1), have evolved a variety of immune evasion strategies to avoid being detected and destroyed by the host's immune system. A dynamic cross talk appears to occur between the HSV-1 latency-associated transcript (LAT), the only viral gene that is abundantly transcribed during latency, and the CD8(+)T cells that reside in HSV-1 latently infected human and rabbit trigeminal ganglia (TG). The reactivation phenotype of TG that are latently infected with wild-type HSV-1 or with LAT-rescued mutant (i.e., LAT(+)TG) is significantly higher than TG latently infected with LAT-null mutant (i.e., LAT(-)TG). Whether LAT promotes virus reactivation by selectively shaping a unique repertoire of HSV-specific CD8(+)T cells in LAT(+)TG is unknown. In the present study, we assessed the frequency, function, and exhaustion status of TG-resident CD8(+)T cells specific to 40 epitopes derived from HSV-1 gB, gD, VP11/12, and VP13/14 proteins, in human leukocyte antigen (HLA-A*0201) transgenic rabbits infected ocularly with LAT(+)versus LAT(-)virus. Compared to CD8(+)T cells from LAT(-)TG, CD8(+)T cells from LAT(+)TG (i) recognized a broader selection of nonoverlapping HSV-1 epitopes, (ii) expressed higher levels of PD-1, TIM-3, and CTLA-4 markers of exhaustion, and (iii) produced less tumor necrosis factor alpha, gamma interferon, and granzyme B. These results suggest a novel immune evasion mechanism by which the HSV-1 LAT may contribute to the shaping of a broader repertoire of exhausted HSV-specific CD8(+)T cells in latently infected TG, thus allowing for increased viral reactivation. IMPORTANCE: A significantly larger repertoire of dysfunctional (exhausted) HSV-specific CD8(+)T cells were found in the TG of HLA transgenic rabbits latently infected with wild-type HSV-1 or with LAT-rescued mutant (i.e., LAT(+)TG) than in a more restricted repertoire of functional HSV-specific CD8(+)T cells in the TG of HLA transgenic rabbits latently infected with LAT-null mutant (i.e., LAT(-)TG). These findings suggest that the HSV-1 LAT locus interferes with the host cellular immune response by shaping a broader repertoire of exhausted HSV-specific CD8(+)T cells within the latency/reactivation TG site. PMID- 26842471 TI - Nuclear Translocation Sequence and Region in Autographa californica Multiple Nucleopolyhedrovirus ME53 That Are Important for Optimal Baculovirus Production. AB - Autographa californicamultiple nucleopolyhedrovirus (AcMNPV) is in the familyBaculoviridae, genusAlphabaculovirus AcMNPVme53is a highly conserved immediate early gene in all lepidopteran baculoviruses that have been sequenced and is transcribed up to late times postinfection. Althoughme53is not essential for viral DNA synthesis, infectious budded virus (BV) production is greatly attenuated when it is deleted. ME53 associates with the nucleocapsid on both budded virus and occlusion-derived virus, but not with the virus envelope. ME53 colocalizes in plasma membrane foci with the envelope glycoprotein GP64 in a GP64 dependent manner. ME53 localizes in the cytoplasm early postinfection, and despite the lack of a reported nuclear localization signal (NLS), ME53 translocates to the nucleus at late times postinfection. To map determinants of ME53 that facilitate its nuclear translocation, recombinant AcMNPV bacmids containing a series of ME53 truncations, internal deletions, and peptides fused with hemagglutinin (HA) or green fluorescent protein (GFP) tags were constructed. Intracellular-localization studies identified residues within amino acids 109 to 137 at the N terminus of ME53 that acted as the nuclear translocation sequence (NTS), facilitating its nuclear transport at late times postinfection. The first 100 N-terminal amino acids and the last 50 C-terminal amino acids of ME53 are dispensable for high levels of budded virus production. The region within amino acids 101 to 398, which also contains the NTS, is critical for optimal levels of budded virus production. IMPORTANCE: Baculovirusme53is a conserved immediate early gene found in all sequenced lepidopteran alpha- and betabaculoviruses. We first identified residues within amino acids 109 to 137 at the N terminus that act as the ME53 nuclear translocation sequence (NTS) to facilitate its nuclear translocation and defined an internal region within amino acids 101 to 398, which includes the NTS, as being necessary for optimal budded virus production. Altogether, these results indicate a previously unidentified nuclear role that ME53 plays in virus replication. PMID- 26842470 TI - A Regulatory Element Near the 3' End of the Adeno-Associated Virus rep Gene Inhibits Adenovirus Replication in cis by Means of p40 Promoter-Associated Short Transcripts. AB - Adeno-associated virus (AAV) has long been known to inhibit helper adenovirus (Ad) replication independently of AAV Rep protein expression. More recently, replication of Ad serotype 5 (Ad5)/AAV serotype 2 (AAV-2) hybrid vectors was shown to be inhibited incisby a sequence near the 3' end of AAVrep, termed the Rep inhibition sequence for adenoviral replication (RIS-Ad). RIS-Ad functions independently of Rep protein expression. Here we demonstrate that inhibition of adenoviral replication by RIS-Ad requires an active AAV p40 promoter and the 5' half of the intron. In addition, Ad inhibition is critically dependent on the integrity of the p40 transcription start site (TSS) leading to short p40 associated transcripts. These do not give rise to effector molecules capable of inhibiting adenoviral replication intrans, like small polypeptides or microRNAs. Our data point to an inhibitory mechanism in which RNA polymerase II (Pol II) pauses directly downstream of the p40 promoter, leading to interference of the stalled Pol II transcription complex with the adenoviral replication machinery. Whereas inhibition by RIS-Ad is mediated exclusively incis, it can be overcome by providing a replication-competent adenoviral genome intrans Moreover, the inhibitory effect of RIS-Ad is not limited to AAV-2 but could also be shown for the corresponding regions of other AAV serotypes, including AAV-5. These findings have important implications for the future generation of Ad5/AAV hybrid vectors. IMPORTANCE: Insertion of sequences from the 3' part of therepgene of adeno associated virus (AAV) into the genome of its helper adenovirus strongly reduces adenoviral genome replication. We could show that this inhibition is mediated exclusively inciswithout the involvement oftrans-acting regulatory RNAs or polypeptides but nevertheless requires an active AAV-2 p40 promoter and p40 associated short transcripts. Our results suggest a novel inhibitory mechanism that has so far not been described for AAV and that involves stalled RNA polymerase II complexes and their interference with adenoviral DNA replication. Such a mechanism would have important implications both for the generation of adenoviral vectors expressing the AAVrepandcapgenes and for the regulation of AAV gene expression in the absence and presence of helper virus. PMID- 26842472 TI - Genetic Stability of Bacterial Artificial Chromosome-Derived Human Cytomegalovirus during Culture In Vitro. AB - Clinical human cytomegalovirus (HCMV) strains invariably mutate when propagatedin vitro Mutations in gene RL13 are selected in all cell types, whereas in fibroblasts mutants in the UL128 locus (UL128L; genes UL128, UL130, and UL131A) are also selected. In addition, sporadic mutations are selected elsewhere in the genome in all cell types. We sought to investigate conditions under which HCMV can be propagated without incurring genetic defects. Bacterial artificial chromosomes (BACs) provide a stable, genetically defined source of viral genome. Viruses were generated from BACs containing the genomes of strains TR, TB40, FIX, and Merlin, as well as from Merlin-BAC recombinants containing variant nucleotides in UL128L from TB40-BAC4 or FIX-BAC. Propagation of viruses derived from TR-BAC, TB40-BAC4, and FIX-BAC in either fibroblast or epithelial cells was associated with the generation of defects around the prokaryotic vector, which is retained in the unique short (US) region of viruses. This was not observed for Merlin-BAC, from which the vector is excised in derived viruses; however, propagation in epithelial cells was consistently associated with mutations in the unique longb' (UL/b') region, all impacting on gene UL141. Viruses derived from Merlin-BAC in fibroblasts had mutations in UL128L, but mutations occurred less frequently with recombinants containing UL128L nucleotides from TB40-BAC4 or FIX BAC. Viruses derived from a Merlin-BAC derivative in which RL13 and UL128L were either mutated or repressed were remarkably stable in fibroblasts. Thus, HCMV containing a wild-type gene complement can be generatedin vitroby deriving virus from a self-excising BAC in fibroblasts and repressing RL13 and UL128L. IMPORTANCE: Researchers should aim to study viruses that accurately represent the causative agents of disease. This is problematic for HCMV because clinical strains mutate rapidly when propagatedin vitro, becoming less cell associated, altered in tropism, more susceptible to natural killer cells, and less pathogenic. Following isolation from clinical material, HCMV genomes can be stabilized by cloning into bacterial artificial chromosomes (BACs), and then virus is regenerated by DNA transfection. However, mutations can occur not only during isolation prior to BAC cloning but also when virus is regenerated. We have identified conditions under which BAC-derived viruses containing an intact, wild type genome can be propagatedin vitrowith minimal risk of mutants being selected, enabling studies of viruses expressing the gene complement of a clinical strain. However, even under these optimized conditions, sporadic mutations can occur, highlighting the advisability of sequencing the HCMV stocks used in experiments. PMID- 26842473 TI - alphavbeta3 Integrin Boosts the Innate Immune Response Elicited in Epithelial Cells through Plasma Membrane and Endosomal Toll-Like Receptors. AB - We report that alphavbeta3 integrin strongly affects the innate immune response in epithelial cells. alphavbeta3 integrin greatly increased the response elicited via plasma membrane Toll-like receptors (TLRs) by herpes simplex virus or bacterial ligands. The endosomal TLR3, not the cytosolic sensor interferon gamma inducible protein 16 (IFI16), was also boosted by alphavbeta3 integrin. The boosting was exerted specifically by alphavbeta3 integrin but not by alphavbeta6 or alphavbeta8 integrin. Current and previous work indicates that integrin-TLR cooperation occurs in epithelial and monocytic cells. The TLR response should be considered an integrin-TLR response. PMID- 26842474 TI - Expansion of Inefficient HIV-Specific CD8 T Cells during Acute Infection. AB - Attrition within the CD4(+)T cell compartment, high viremia, and a cytokine storm characterize the early days after HIV infection. When the first emerging HIV specific CD8(+)T cell responses gain control over viral replication it is incomplete, and clearance of HIV infection is not achieved even in the rare cases of individuals who spontaneously control viral replication to nearly immeasurably low levels. Thus, despite their partial ability to control viremia, HIV-specific CD8(+)T cell responses are insufficient to clear HIV infection. Studying individuals in the first few days of acute HIV infection, we detected the emergence of a unique population of CD38(+)CD27(-)CD8(+)T cells characterized by the low expression of the CD8 receptor (CD8(dim)). Interestingly, while high frequencies of HIV-specific CD8(+)T cell responses occur within the CD38(+)CD27( )CD8(dim)T cell population, the minority populations of CD8(bright)T cells are significantly more effective in inhibiting HIV replication. Furthermore, the frequency of CD8(dim)T cells directly correlates with viral load and clinical predictors of more rapid disease progression. We found that a canonical burst of proliferative cytokines coincides with the emergence of CD8(dim)T cells, and the size of this population inversely correlates with the acute loss of CD4(+)T cells. These data indicate, for the first time, that early CD4(+)T cell loss coincides with the expansion of a functionally impaired HIV-specific CD8(dim)T cell population less efficient in controlling HIV viremia. IMPORTANCE: A distinct population of activated CD8(+)T cells appears during acute HIV infection with diminished capacity to inhibit HIV replication and is predictive of viral set point, offering the first immunologic evidence of CD8(+)T cell dysfunction during acute infection. PMID- 26842475 TI - Hepatitis B Virus Capsids Have Diverse Structural Responses to Small-Molecule Ligands Bound to the Heteroaryldihydropyrimidine Pocket. AB - Though the hepatitis B virus (HBV) core protein is an important participant in many aspects of the viral life cycle, its best-characterized activity is self assembly into 240-monomer capsids. Small molecules that target core protein (core protein allosteric modulators [CpAMs]) represent a promising antiviral strategy. To better understand the structural basis of the CpAM mechanism, we determined the crystal structure of the HBV capsid in complex with HAP18. HAP18 accelerates assembly, increases protein-protein association more than 100-fold, and induces assembly of nonicosahedral macrostructures. In a preformed capsid, HAP18 is found at quasiequivalent subunit-subunit interfaces. In a detailed comparison to the two other extant CpAM structures, we find that the HAP18-capsid structure presents a paradox. Whereas the two other structures expanded the capsid diameter by up to 10 A, HAP18 caused only minor changes in quaternary structure and actually decreased the capsid diameter by ~3 A. These results indicate that CpAMs do not have a single allosteric effect on capsid structure. We suggest that HBV capsids present an ensemble of states that can be trapped by CpAMs, indicating a more complex basis for antiviral drug design. IMPORTANCE: Hepatitis B virus core protein has multiple roles in the viral life cycle-assembly, compartment for reverse transcription, intracellular trafficking, and nuclear functions-making it an attractive antiviral target. Core protein allosteric modulators (CpAMs) are an experimental class of antivirals that bind core protein. The most recognized CpAM activity is that they accelerate core protein assembly and strengthen interactions between subunits. In this study, we observe that the CpAM-binding pocket has multiple conformations. We compare structures of capsids cocrystallized with different CpAMs and find that they also affect quaternary structure in different ways. These results suggest that the capsid "breathes" and is trapped in different states by the drug and crystallization. Understanding that the capsid is a moving target will aid drug design and improve our understanding of HBV interaction with its environment. PMID- 26842477 TI - Virus and Host Mechanics Support Membrane Penetration and Cell Entry. AB - Viruses are quasi-inert macromolecular assemblies. Their metastable conformation changes during entry into cells, when chemical and mechanical host cues expose viral membrane-interacting proteins. This leads to membrane rupture or fusion and genome uncoating. Importantly, virions tune their physical properties and enhance penetration and uncoating. For example, influenza virus softens at low pH to uncoat. The stiffness and pressure of adenovirus control uncoating and membrane penetration. Virus and host mechanics thus present new opportunities for antiviral therapy. PMID- 26842478 TI - The Barrier to Autointegration Factor: Interlocking Antiviral Defense with Genome Maintenance. AB - Intrinsic defenses targeting foreign DNA are one facet of the cellular armament tasked with protecting host genomic integrity. The DNA binding protein BAF (barrier to autointegration factor) contributes to multiple aspects of genome maintenance and intercepts retrovirus, poxvirus, and herpesvirus genomes during infection. In this gem, we discuss the unique position BAF occupies at the virus host interface and how both viral and cellular mechanisms may regulate its capacity to act as a pro- or antiviral effector targeting viral DNA. PMID- 26842476 TI - Development of Broadly Neutralizing Antibodies and Their Mapping by Monomeric gp120 in Human Immunodeficiency Virus Type 1-Infected Humans and Simian-Human Immunodeficiency Virus SHIVSF162P3N-Infected Macaques. AB - To improve our understanding of the similarities and differences between neutralizing antibodies elicited by simian-human immunodeficiency virus (SHIV) infected rhesus macaques and human immunodeficiency virus type 1 (HIV-1)-infected humans, we examined the plasma of 13 viremic macaques infected with SHIVSF162P3Nand 85 HIV-1-infected humans with known times of infection. We identified 5 macaques (38%) from 1 to 2 years postinfection (p.i.) with broadly neutralizing antibodies (bnAbs) against tier 2 HIV-1. In comparison, only 2 out of 42 (5%) human plasma samples collected in a similar time frame of 1 to 3 years p.i. exhibited comparable neutralizing breadths and potencies, with the number increasing to 7 out of 21 (30%) after 3 years p.i. Plasma mapping with monomeric gp120 identified only 2 out of 9 humans and 2 out of 4 macaques that contained gp120-reactive neutralizing antibodies, indicating distinct specificities in these plasma samples, with most of them recognizing the envelope trimer (including gp41) rather than the gp120 monomer. Indeed, a total of 20 gp120 directed monoclonal antibodies (MAbs) isolated from a human subject (AD358) and a Chinese rhesus macaque (GB40) displayed no or limited neutralizing activity against tier 2 strains. These isolated MAbs, mapped to the CD4-binding site, the V3 loop, the inner domain, and the C5 region of gp120, revealed genetic similarity between the human and macaque immunoglobulin genes used to encode some V3-directed MAbs. These results also support the use of envelope trimer probes for efficient isolation of HIV-1 bnAbs. IMPORTANCE: HIV-1 vaccine research can benefit from understanding the development of broadly neutralizing antibodies (bnAbs) in rhesus macaques, commonly used to assess vaccine immunogenicity and efficacy. Here, we examined 85 HIV-1-infected humans and 13 SHIVSF162P3N-infected macaques for bnAbs and found that, similar to HIV-1-infected humans, bnAbs in SHIV-infected macaques are also rare, but their development might have been faster in some of the studied macaques. Plasma mapping with monomeric gp120 indicated that most bnAbs bind to the envelope trimer rather than the gp120 monomer. In support of this, none of the isolated gp120-reactive monoclonal antibodies (MAbs) displayed the neutralization breadth observed in the corresponding plasma. However, the MAb sequences revealed similarity between human and macaque genes used to encode some V3-directed MAbs. Our study sheds light on the timing and development of bnAbs in SHIV-infected macaques in comparison to HIV-1-infected humans and highlights the use of envelope trimer probes for efficient recovery of bnAbs. PMID- 26842480 TI - gD-Independent Superinfection Exclusion of Alphaherpesviruses. AB - Many viruses have the capacity to prevent a cell from being infected by a second virus, often termed superinfection exclusion. Alphaherpesviruses, including the human pathogen herpes simplex virus 1 (HSV-1) and the animal herpesvirus pseudorabies virus (PRV), encode a membrane-bound glycoprotein, gD, that can interfere with subsequent virion entry. We sought to characterize the timing and mechanism of superinfection exclusion during HSV-1 and PRV infection. To this end, we utilized recombinant viruses expressing fluorescent protein (FP) markers of infection that allowed the visualization of viral infections by microscopy and flow cytometry as well as the differentiation of viral progeny. Our results demonstrated the majority of HSV-1- and PRV-infected cells establish superinfection exclusion by 2 h postinfection. The modification of viral infections by virion inactivation and phosphonoacetic acid, cycloheximide, and actinomycin D treatments indicated new protein synthesis is needed to establish superinfection exclusion. Primary infection with gene deletion PRV recombinants identified that new gD expression is not required to establish superinfection exclusion of a secondary viral inoculum. We also identified the timing of coinfection events during axon-to-cell spread, with most occurring within a 2-h window, suggesting a role for cellular superinfection exclusion during neuroinvasive spread of infection. In summary, we have characterized a gD independent mechanism of superinfection exclusion established by two members of the alphaherpesvirus family and identified a potential role of exclusion during the pathogenic spread of infection. IMPORTANCE: Superinfection exclusion is a widely observed phenomenon initiated by a primary viral infection to prevent further viruses from infecting the same cell. The capacity for alphaherpesviruses to infect the same cell impacts rates of interviral recombination and disease. Interviral recombination allows genome diversification, facilitating the development of resistance to antiviral therapeutics and evasion of vaccine mediated immune responses. Our results demonstrate superinfection exclusion occurs early, through a gD-independent process, and is important in the directed spread of infection. Identifying when and where in an infected host viral genomes are more likely to coinfect the same cell and generate viral recombinants will enhance the development of effective antiviral therapies and interventions. PMID- 26842479 TI - Prime, Shock, and Kill: Priming CD4 T Cells from HIV Patients with a BCL-2 Antagonist before HIV Reactivation Reduces HIV Reservoir Size. AB - Understanding how some HIV-infected cells resist the cytotoxicity of HIV replication is crucial to enabling HIV cure efforts. HIV killing of CD4 T cells that replicate HIV can involve HIV protease-mediated cleavage of procaspase 8 to generate a fragment (Casp8p41) that directly binds and activates the mitochondrial proapoptotic protein BAK. Here, we demonstrate that Casp8p41 also binds with nanomolar affinity to the antiapoptotic protein Bcl-2, which sequesters Casp8p41 and prevents apoptosis. Further, we show that central memory CD4 T cells (TCM) from HIV-infected individuals have heightened expression of BCL 2 relative to procaspase 8, possibly explaining the persistence of HIV-infected TCMdespite generation of Casp8p41. Consistent with this hypothesis, the selective BCL-2 antagonist venetoclax induced minimal killing of uninfected CD4 T cells but markedly increased the death of CD4 T cells and diminished cell-associated HIV DNA when CD4 T cells from antiretroviral therapy (ART)-suppressed HIV patients were induced with alphaCD3/alphaCD28 to reactivate HIVex vivo Thus, priming CD4 T cells from ART suppressed HIV patients with a BCL-2 antagonist, followed by HIV reactivation, achieves reductions in cell-associated HIV DNA, whereas HIV reactivation alone does not. IMPORTANCE: HIV infection is incurable due to a long lived reservoir of HIV(+)memory CD4 T cells, and no clinically relevant interventions have been identified that reduce the number of these HIV DNA containing cells. Since postintegration HIV replication can result in HIV protease generation of Casp8p41, which activates BAK, causing infected CD4 T cell death, we sought to determine whether this occurs in memory CD4 T cells. Here, we demonstrate that memory CD4 T cells can generate Casp8p41 and yet are intrinsically resistant to death induced by diverse stimuli, including Casp8p41. Furthermore, BCL-2 expression is relatively increased in these cells and directly binds and inhibits Casp8p41's proapoptotic effects. Antagonizing BCL-2 with venetoclax derepresses this antagonism, resulting in death, preferentially in HIV DNA containing cells, since only these cells generate Casp8p41. Thus, BCL-2 antagonism is a clinically relevant intervention with the potential to reduce HIV reservoir size in patients. PMID- 26842482 TI - Efficacy, Acceptability, and Tolerability of Antipsychotics in Treatment Resistant Schizophrenia: A Network Meta-analysis. AB - IMPORTANCE: In treatment-resistant schizophrenia, clozapine is considered the standard treatment. However, clozapine use has restrictions owing to its many adverse effects. Moreover, an increasing number of randomized clinical trials (RCTs) of other antipsychotics have been published. OBJECTIVE: To integrate all the randomized evidence from the available antipsychotics used for treatment resistant schizophrenia by performing a network meta-analysis. DATA SOURCES: MEDLINE, EMBASE, Biosis, PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, World Health Organization International Trial Registry, and clinicaltrials.gov were searched up to June 30, 2014. STUDY SELECTION: At least 2 independent reviewers selected published and unpublished single- and double-blind RCTs in treatment-resistant schizophrenia (any study-defined criterion) that compared any antipsychotic (at any dose and in any form of administration) with another antipsychotic or placebo. DATA EXTRACTION AND SYNTHESIS: At least 2 independent reviewers extracted all data into standard forms and assessed the quality of all included trials with the Cochrane Collaboration's risk-of-bias tool. Data were pooled using a random-effects model in a Bayesian setting. MAIN OUTCOMES AND MEASURES: The primary outcome was efficacy as measured by overall change in symptoms of schizophrenia. Secondary outcomes included change in positive and negative symptoms of schizophrenia, categorical response to treatment, dropouts for any reason and for inefficacy of treatment, and important adverse events. RESULTS: Forty blinded RCTs with 5172 unique participants (71.5% men; mean [SD] age, 38.8 [3.7] years) were included in the analysis. Few significant differences were found in all outcomes. In the primary outcome (reported as standardized mean difference; 95% credible interval), olanzapine was more effective than quetiapine (-0.29; -0.56 to -0.02), haloperidol (-0. 29; 0.44 to -0.13), and sertindole (-0.46; -0.80 to -0.06); clozapine was more effective than haloperidol (-0.22; -0.38 to -0.07) and sertindole (-0.40; -0.74 to -0.04); and risperidone was more effective than sertindole (-0.32; -0.63 to 0.01). A pattern of superiority for olanzapine, clozapine, and risperidone was seen in other efficacy outcomes, but results were not consistent and effect sizes were usually small. In addition, relatively few RCTs were available for antipsychotics other than clozapine, haloperidol, olanzapine, and risperidone. The most surprising finding was that clozapine was not significantly better than most other drugs. CONCLUSIONS AND RELEVANCE: Insufficient evidence exists on which antipsychotic is more efficacious for patients with treatment-resistant schizophrenia, and blinded RCTs-in contrast to unblinded, randomized effectiveness studies-provide little evidence of the superiority of clozapine compared with other second-generation antipsychotics. Future clozapine studies with high doses and patients with extremely treatment-refractory schizophrenia might be most promising to change the current evidence. PMID- 26842481 TI - Promoter-Targeted Histone Acetylation of Chromatinized Parvoviral Genome Is Essential for the Progress of Infection. AB - The association of host histones with parvoviral DNA is poorly understood. We analyzed the chromatinization and histone acetylation of canine parvovirus DNA during infection by confocal imaging andin situproximity ligation assay combined with chromatin immunoprecipitation and high-throughput sequencing. We found that during late infection, parvovirus replication bodies were rich in histones bearing modifications characteristic of transcriptionally active chromatin, i.e., histone H3 lysine 27 acetylation (H3K27ac). H3K27ac, in particular, was located in close proximity to the viral DNA-binding protein NS1. Importantly, our results show for the first time that in the chromatinized parvoviral genome, the two viral promoters in particular were rich in H3K27ac. Histone acetyltransferase (HAT) inhibitors efficiently interfered with the expression of viral proteins and infection progress. Altogether, our data suggest that the acetylation of histones on parvoviral DNA is essential for viral gene expression and the completion of the viral life cycle. IMPORTANCE: Viral DNA introduced into cell nuclei is exposed to cellular responses to foreign DNA, including chromatinization and epigenetic silencing, both of which determine the outcome of infection. How the incoming parvovirus resists cellular epigenetic downregulation of its genes is not understood. Here, the critical role of epigenetic modifications in the regulation of parvovirus infection was demonstrated. We showed for the first time that a successful parvovirus infection is characterized by the deposition of nucleosomes with active histone acetylation on the viral promoter areas. The results provide new insights into the regulation of parvoviral gene expression, which is an important aspect of the development of parvovirus-based virotherapy. PMID- 26842483 TI - Spatial distribution mapping of drinking water fluoride levels in Karnataka, India: fluoride-related health effects. AB - OBJECTIVES: (1) To estimate the concentrations of fluoride in drinking water throughout different zones and districts of the state of Karnataka. (2) To investigate the variation of fluoride concentration in drinking water from different sources, and its relationships to daily temperature and rainfall status in the regional districts. (3) To develop an updated fluoride concentration intensity map of the state of Karnataka, and to evaluate these data in the context of fluoride-related health effects such as fluorosis and their prevalence. MATERIALS AND METHODS: Aqueous standard solutions of 10, 100 and 1,000 ppm fluoride (F-) were prepared with analytical grade Na+/F- and a buffer; TISAB II was incorporated in both calibration standard and analysis solutions in order to remove the potentially interfering effects of trace metal ions. This analysis was performed using an ion-selective electrode (ISE), and mean determination readings for n = 5 samples collected at each Karnataka water source were recorded. RESULTS: The F- concentration in drinking water in Karnataka state was found to vary substantially, with the highest mean values recorded being in the north-eastern zone (1.61 ppm), and the lowest in the south-western one (only 0.41 ppm). Analysis of variance (ANOVA) demonstrated that there were very highly significant 'between-zone' and 'between-districts-within-zones' sources of variation (p < 10-5-10-9), results consistent with a substantial spatial variance of water source F- levels within this state. CONCLUSIONS: The southern part of Karnataka has low levels of F- in its drinking water, and may require fluoridation treatment in order to mitigate for dental caries and further ailments related to fluoride deficiency. However, districts within the north eastern region have contrastingly high levels of fluoride, an observation which has been linked to dental and skeletal fluorosis. This highlights a major requirement for interventional actions in order to ensure maintenance of the recommended range of fluoride concentrations (0.8-1.5 ppm) in Karnataka's drinking water sources. PMID- 26842485 TI - Important Limitations in Defining the Benefits of Bariatric Surgery for Patients With Type 2 Diabetes. PMID- 26842484 TI - Vessel Dilation Attenuates Endothelial Dysfunction Following Middle Cerebral Artery Occlusion in Hyperglycemic Rats. AB - OBJECTIVES: Dynamically observe cerebral vascular changes in hyperglycemic rats in vivo and explore the effect of diabetes on endothelial function after ischemic stroke. BACKGROUND: Diabetes affects both large and small vessels in the brain, but the dynamic process and mechanism are unclear. METHODS: We investigated the structural and functional changes of brain vasculature in living hyperglycemic rats and their impact on stroke outcomes via a novel technique: synchrotron radiation angiography. We also examined the effect of prolonged fasudil treatment on arterial reactivity and hemorrhagic transformation. Adult Sprague Dawley rats were treated by streptozotocin to induce type 1 diabetes. These hyperglycemic rats received fasudil pretreatment and then underwent transient middle cerebral artery occlusion. RESULTS: We found that diabetes caused arteries narrowing in the circus Willis as early as 2 weeks after streptozotocin injection (P < 0.05). These vessels were further constricted after middle cerebral artery occlusion. L NAME could induce regional constrictions and impaired relaxation in hyperglycemic animals. Furthermore, hemorrhagic transformation was also increased in the hyperglycemic rats compared to the control (P < 0.05). In fasudil-treated rats, the internal carotid artery narrowing was ameliorated and L-NAME-induced regional constriction was abolished. Importantly, stroke prognosis was improved in fasudil treated rats compared to the control (P < 0.05). CONCLUSIONS: Our dynamic angiographic data demonstrated that diabetes could impair the cerebral arterial reactivity. Prolonged fasudil treatment could attenuate arterial dysfunction and improve the prognosis of ischemic stroke by affecting both the large and small vasculature. PMID- 26842486 TI - A Survey of American and Canadian Psychiatry Residents on Their Training, Teaching Practices, and Attitudes Toward Teaching. AB - OBJECTIVE: Formal training for residents-as-teachers in psychiatry is increasingly emphasized. However, little is known about the quantity and content of residents' teaching, their attitudes toward teaching, or the training received on how to teach. METHODS: An online survey was disseminated to American and Canadian psychiatry residents. RESULTS: Three hundred eighty-two residents from all postgraduate years (PGY) responded, representing about 7 % of all trainees. About half of PGY-1 have not received residents-as-teachers training, but by PGY 3 most have. The majority of respondents reported teaching, most commonly 1-5 h. Most found teaching enjoyable or rewarding (n = 304; 87 %); however, 40 % (n = 138) found teaching burdensome, 43 % (n = 151) lacked sufficient time to teach, and many (n = 226; 64 %) reported insufficient feedback from supervisors. CONCLUSIONS: Although the sampling methodology and low response rate limit the generalizability of findings, respondents typically seemed to value teaching, though the majority felt that they lacked feedback on their teaching skills. PMID- 26842487 TI - In Vivo Feasibility of Electrostatic Precipitation as an Adjunct to Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC). AB - BACKGROUND: Intraperitoneal chemotherapy is limited by tissue penetration. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been shown to improve drug uptake by utilizing the physical properties of gas and pressure. This study investigated the effect of adding electrostatic precipitation to further enhance the pharmacologic properties of this technique. METHODS: A comparative study was performed using an in vivo porcine model. There were 3 cases in each group, PIPAC and electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy (ePIPAC), plus 1 negative control comparing intraperitoneal distribution and tissue uptake of 2 tracer substances (toluidine blue and DT01). Tracer uptake was determined by measuring DT01 in tissue and peritoneal fluid at the end of each procedure. RESULTS: Electrostatic precipitation of the aerosol was technically feasible in all ePIPAC animals. The aerosol was cleared completely from the visual field within 15 s in the ePIPAC group versus 30 min in the PIPAC group. The peritoneal surface was homogeneously stained in both groups. After 30 min, 1.5 % remaining DT01 was measured in samples of ePIPAC-treated peritoneal fluid versus 15 % in PIPAC animals (p = 0.01). Tissue concentration was increased after ePIPAC versus PIPAC (p = 0.06). CONCLUSIONS: ePIPAC is technically feasible and improves tissue uptake of 2 tracer substances compared to PIPAC by up to tenfold. Intraperitoneal distribution was homogeneous in both groups. ePIPAC has the potential to allow more efficient drug uptake, further dose reduction, a significant shortening of the time required for PIPAC application, and improved health and safety measures. PMID- 26842488 TI - Minor Components of Micropapillary and Solid Subtypes in Lung Adenocarcinoma are Predictors of Lymph Node Metastasis and Poor Prognosis. AB - BACKGROUND: Lung adenocarcinoma with micropapillary and solid predominant subtypes was reported to be associated with poor prognosis; however, whether minor components (non-predominant) of micropapillary and solid subtypes predict poor prognosis remains unknown. In this study, we investigated the predictive and prognostic value of lymph node metastasis of minor micropapillary and solid components. METHODS: Specimens of resected tumors of 1244 patients were reclassified to determine the predominant subtype and minor components (>5 %, but not predominant). Of these specimens, 105 contained a micropapillary component and 210 contained a solid component. The correlation between each subtype and lymph node metastasis was analyzed, and survival analyses were used to determine the association between each subtype and patient survival. RESULTS: Adenocarcinomas harboring micropapillary and/or solid components held higher rates of metastatic lymph node stations (25.2 % vs. 15.6 %, p = 0.002; and 24.0 % vs. 14.9 %, p < 0.001, respectively) and lymph nodes (17.3 % vs. 10.1 %, p = 0.004; and 15.5 % vs. 9.7 %, p = 0.001, respectively). Patients with micropapillary and solid components in their tumors showed a shorter median recurrence-free survival (15.8 vs. 62.8 months, p < 0.001; and 20.8 months vs. not reached, p < 0.001) and overall survival (47.0 months vs. not reached, p < 0.001; and 69.0 months vs. not reached, p < 0.001). CONCLUSIONS: Minor components of micropapillary and/or solid subtypes of lung adenocarcinoma are correlated with lymph node metastasis and poor prognosis. Thus, it is beneficial to focus not only on predominant subtypes but also minor components to predict prognoses and make therapeutic strategies more comprehensively. PMID- 26842489 TI - Factors Associated with Readmission After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis. AB - PURPOSE: Cytoreductive surgery/hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for peritoneal carcinomatosis is a morbid endeavor. Despite improvement in perioperative management of these patients, there are subsets of patients requiring hospital readmission after discharge. We sought to identify variables associated with readmission rates for CRS/HIPEC. METHODS: We conducted a retrospective review of CRS/HIPEC cases at the University of Cincinnati between 1999 and 2014. Patient-, tumor-, and treatment-specific characteristics were evaluated. The association between patient- and outcome-specific variables for 30 and 90-day readmission were evaluated. RESULTS: Of 215 CRS/HIPEC patients, the 7 , 30-, and 90-day readmission rates were 9.8 % (n = 21), 14.9 % (n = 32), and 21.4 % (n = 46), respectively. The most common reasons for readmission within 90 days included abdominal pain (n = 14), intra-abdominal abscess (n = 9), malnutrition/failure to thrive (n = 8), and bowel obstruction (n = 7). The primary factor associated with readmission at all time points (7, 30, and 90 days) was the presence of an enterocutaneous fistula (p < 0.01). Six patients (2.8 %) had multiple readmissions; 3 of these had ECF. Factors not associated with higher admission rates included sex, age, race, operative blood loss, pancreatectomy or liver resection at the index operation, and postoperative complications of wound infection, line infection, and thromboembolic events. CONCLUSIONS: In patients undergoing CRS/HIPEC, readmission was primarily associated with poor pain control, malnutrition, and infectious complications. Patients with enterocutaneous fistula were also disproportionately readmitted multiple times. These data should inform clinicians about patients at high risk for readmission after CRS/HIPEC and encourage more comprehensive coordination of postdischarge planning and care for specific patient populations. PMID- 26842490 TI - Using Multilevel Models to Explain Variation in Clinical Practice: Surgeon Volume and the Surgical Treatment of Breast Cancer. AB - PURPOSE: To investigate the relationship between surgeon caseload and surgery type, and variation in the surgical treatment of early stage breast cancer patients in Alberta, Canada. METHODS: All women diagnosed with stage I to III breast cancer in Alberta from 2002 to 2010 were identified from the Alberta Cancer Registry. Type of surgery, surgeon (anonymized), and hospital were obtained from provincial physician claims data. Multilevel logistic regression with surgeons and hospitals as crossed random effects was used to estimate adjusted odds ratios (OR) of receiving mastectomy by surgeon volume. Empirical Bayes estimation was used to estimate adjusted OR for individual surgeons and hospitals. RESULTS: Mastectomy was found to be inversely related to surgeon volume among stage I and II patients. Patients whose surgery was conducted by a low-volume surgeon had twice the odds of receiving mastectomy as those that had surgery performed by a very high-volume surgeon (stage I OR 2.36, 95 % confidence interval 1.40, 3.97; stage II OR 1.96, 95 % confidence interval 1.13, 3.42). OR of mastectomy varied widely by individual surgeon beyond the variation explained by the factors investigated. CONCLUSIONS: Surgeon characteristics, including surgeon volume, are associated with surgery type received by breast cancer patients in Alberta. Significant variation in the likelihood of breast-conserving surgery (BCS) by surgeon is concerning given the potential benefits of BCS for those who are eligible. PMID- 26842491 TI - Oncoplastic Breast-Conserving Surgery for Tumors Larger than 2 Centimeters: Is it Oncologically Safe? A Matched-Cohort Analysis. AB - BACKGROUND: Oncoplastic surgery is a well-established approach that combines conserving treatment for breast cancer and plastic surgery techniques. Although this approach has been described for T2 tumors, no long-term oncologic follow-up and no comparison with patients undergoing mastectomy has been published. The purpose of the study was to demonstrate that oncoplastic surgery is a safe and reliable treatment for managing invasive primary T2 breast cancer. METHODS: We compared a consecutive series of 193 T2 patients who have undergone oncoplastic surgery (study group) with 386 T2 patients who have undergone mastectomy (control group). The endpoints evaluated were disease-free survival (DFS), overall survival (OS), cumulative incidence of local recurrence (CI-L), regional recurrence (CI-R), and distant recurrence (CI-D), all measured from the date of surgery. RESULTS: Median follow-up is 7.4 years. The OS is similar within the two groups: 87.3 and 87.1 % at 10 years in the ONC group and control group, respectively (p value, adjusted for multifocality and tumor size, 0.74). Also, the DFS is similar in both groups: 60.9 and 56.3 % at 10 years in the ONC group and control group, respectively. The incidence of local events is slightly higher in the oncoplastic group, whereas the incidence of regional events is slightly higher in the mastectomy group. These differences are not statistically significant. The cumulative incidence of distant events is similar within the two groups. CONCLUSIONS: To our knowledge, the present study provides the best available evidence to suggest that oncoplastic approach is a safe and reliable treatment for managing invasive pT2 breast cancers. PMID- 26842492 TI - Local Recurrence in the Lateral Lymph Node Compartment: Improved Outcomes with Induction Chemotherapy Combined with Multimodality Treatment. AB - BACKGROUND: Lateral nodal disease is of major importance in the treatment of rectal cancer in the East, but a mostly neglected entity in the West. In this article, the treatment of recurrences in the lateral compartment (latLRs) in a national tertiary referral center is evaluated. METHODS: Of 214 patients with locally recurrent rectal cancer who underwent multimodality treatment in the Catharina Hospital in the last 10 years, a total of 51 patients with latLR were selected (the latLR region was classified as upper, middle, or lower). Thirteen (25 %) of these patients underwent induction chemotherapy (ICT) prior to chemo(re)irradiation. RESULTS: LatLRs occurred mainly after low and N+ primary tumors. Seven (14 %) patients had a complete response (pCR) and 28 (55 %) underwent an R0 resection. Patients with a lower latLR had the highest chance of undergoing an abdominoperineal resection and resection of anterior organs. ICT resulted in a 31 % pCR rate compared with 8 % without ICT (p = 0.039). Patients who received ICT had an 85 % R0 resection rate, while this was 45 % in patients who did not receive ICT (p = 0.013). The 5-year local re-recurrence (LRR) rate was 64.3 %, and overall survival (OS) was 34.2 %; the only factor improving these was an R0 resection. Five-year survival after multivariate analyses was 10.3 % after an R+ resection compared with 66.8 % after an R0 resection (p = 0.011). CONCLUSIONS: LatLRs impose a major surgical challenge and result in high LRR and low OS. More R0 resections can possibly be achieved with ICT, which is the only factor that can improve LRR and OS. PMID- 26842494 TI - Differential contribution of genomic regions to marked genetic variation and prediction of quantitative traits in broiler chickens. AB - BACKGROUND: Genome-wide association studies in humans have found enrichment of trait-associated single nucleotide polymorphisms (SNPs) in coding regions of the genome and depletion of these in intergenic regions. However, a recent release of the ENCyclopedia of DNA elements showed that ~80 % of the human genome has a biochemical function. Similar studies on the chicken genome are lacking, thus assessing the relative contribution of its genic and non-genic regions to variation is relevant for biological studies and genetic improvement of chicken populations. METHODS: A dataset including 1351 birds that were genotyped with the 600K Affymetrix platform was used. We partitioned SNPs according to genome annotation data into six classes to characterize the relative contribution of genic and non-genic regions to genetic variation as well as their predictive power using all available quality-filtered SNPs. Target traits were body weight, ultrasound measurement of breast muscle and hen house egg production in broiler chickens. Six genomic regions were considered: intergenic regions, introns, missense, synonymous, 5' and 3' untranslated regions, and regions that are located 5 kb upstream and downstream of coding genes. Genomic relationship matrices were constructed for each genomic region and fitted in the models, separately or simultaneously. Kernel-based ridge regression was used to estimate variance components and assess predictive ability. Contribution of each class of genomic regions to dominance variance was also considered. RESULTS: Variance component estimates indicated that all genomic regions contributed to marked additive genetic variation and that the class of synonymous regions tended to have the greatest contribution. The marked dominance genetic variation explained by each class of genomic regions was similar and negligible (~0.05). In terms of prediction mean-square error, the whole-genome approach showed the best predictive ability. CONCLUSIONS: All genic and non-genic regions contributed to phenotypic variation for the three traits studied. Overall, the contribution of additive genetic variance to the total genetic variance was much greater than that of dominance variance. Our results show that all genomic regions are important for the prediction of the targeted traits, and the whole-genome approach was reaffirmed as the best tool for genome-enabled prediction of quantitative traits. PMID- 26842495 TI - A combination of traditional learning and e-learning can be more effective on radiological interpretation skills in medical students: a pre- and post intervention study. AB - BACKGROUND: The ability to interpret an X-Ray is a vital skill for graduating medical students which guides clinicians towards accurate diagnosis and treatment of the patient. However, research has suggested that radiological interpretation skills are less than satisfactory in not only medical students, but also in residents and consultants. METHODS: This study investigated the effectiveness of e-learning for the development of X-ray interpretation skills in pre-clinical medical students. Competencies in clinical X-Ray interpretation were assessed by comparison of pre- and post-intervention scores and one year follow up assessment, where the e-learning course was the 'intervention'. RESULTS: Our results demonstrate improved knowledge and skills in X-ray interpretation in students. Assessment of the post training students showed significantly higher scores than the scores of control group of students undertaking the same assessment at the same time. CONCLUSIONS: The development of the Internet and advances in multimedia technologies has paved the way for computer-assisted education. As more rural clinical schools are established the electronic delivery of radiology teaching through websites will become a necessity. The use of e learning to deliver radiology tuition to medical students represents an exciting alternative and is an effective method of developing competency in radiological interpretation for medical students. PMID- 26842496 TI - Interleukin 1 beta (IL1beta) rs16944 genetic variant as a genetic marker of severe renal manifestations and renal sequelae in Henoch-Schonlein purpura. AB - OBJECTIVES: Data from a small series suggested that the Interleukin 1 beta (IL1beta) rs16944 polymorphism may be associated with severe renal involvement and persistent renal damage (renal sequelae) in Henoch-Schonlein purpura (HSP). To confirm this association, we assessed the largest cohort of Caucasian HSP patients ever considered for genetic studies. METHODS: 338 Spanish HSP patients and 635 sex and ethnically matched controls were recruited in this study. All patients were required to have had at least 6 months' follow-up. Patients and controls were genotyped for IL1beta rs16944 by TaqMan genotyping assay. RESULTS: No differences between IL1beta rs16944 genotype or allele frequencies were found either in the case/control study or when HSP patients were stratified according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Nevertheless, 4 (25%) of the 16 HSP patients who developed severe renal manifestations carried the TT genotype versus 29 (9%) of 322 who did not develop this complication (p=0.01, OR=5.48, 95% CI: 1.01-28.10). Accordingly, patients carrying the mutant T allele had an increased risk of developing severe nephropathy (p=0.016, OR=2.35, 95% CI: 1.09-5.07). Additionally, a significant increase of the TT genotype was observed in patients with persistent renal damage when compared with those patients without this complication (25% versus 8.6%, respectively; p=0.0035, OR=4.90, 95% CI: 1.26- 18.51). Moreover, renal sequelae were more common in patients carrying the mutant T allele (p=0.0076, OR=2.20, 95% CI: 1.17-4.14). CONCLUSIONS: Our results support that the IL1beta rs16944 polymorphism may be a potential marker of severe renal manifestations and renal sequelae in HSP. PMID- 26842498 TI - Evidence for link between modelled trends in Antarctic sea ice and underestimated westerly wind changes. AB - Despite global warming, total Antarctic sea ice coverage increased over 1979 2013. However, the majority of Coupled Model Intercomparison Project phase 5 models simulate a decline. Mechanisms causing this discrepancy have so far remained elusive. Here we show that weaker trends in the intensification of the Southern Hemisphere westerly wind jet simulated by the models may contribute to this disparity. During austral summer, a strengthened jet leads to increased upwelling of cooler subsurface water and strengthened equatorward transport, conducive to increased sea ice. As the majority of models underestimate summer jet trends, this cooling process is underestimated compared with observations and is insufficient to offset warming in the models. Through the sea ice-albedo feedback, models produce a high-latitude surface ocean warming and sea ice decline, contrasting the observed net cooling and sea ice increase. A realistic simulation of observed wind changes may be crucial for reproducing the recent observed sea ice increase. PMID- 26842493 TI - Clinical delineation of the PACS1-related syndrome--Report on 19 patients. AB - We report on 19 individuals with a recurrent de novo c.607C>T mutation in PACS1. This specific mutation gives rise to a recognizable intellectual disability syndrome. There is a distinctive facial appearance (19/19), characterized by full and arched eyebrows, hypertelorism with downslanting palpebral fissures, long eye lashes, ptosis, low set and simple ears, bulbous nasal tip, wide mouth with downturned corners and a thin upper lip with an unusual "wavy" profile, flat philtrum, and diastema of the teeth. Intellectual disability, ranging from mild to moderate, was present in all. Hypotonia is common in infancy (8/19). Seizures are frequent (12/19) and respond well to anticonvulsive medication. Structural malformations are common, including heart (10/19), brain (12/16), eye (10/19), kidney (3/19), and cryptorchidism (6/12 males). Feeding dysfunction is presenting in infancy with failure to thrive (5/19), gastroesophageal reflux (6/19), and gastrostomy tube placement (4/19). There is persistence of oral motor dysfunction. We provide suggestions for clinical work-up and management and hope that the present study will facilitate clinical recognition of further cases. PMID- 26842497 TI - MicroRNAs as early toxicity signatures of doxorubicin in human-induced pluripotent stem cell-derived cardiomyocytes. AB - An in depth investigation at the genomic level is needed to identify early human relevant cardiotoxicity biomarkers that are induced by drugs and environmental toxicants. The main objective of this study was to investigate the role of microRNAs (miRNAs) as cardiotoxicity biomarkers using human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) that were exposed to doxorubicin (DOX) as a "gold standard" cardiotoxicant. hiPSC-CMs were exposed to 156 nM DOX for 2 days or for 6 days of repeated exposure, followed by drug washout and incubation in drug-free culture medium up to day 14 after the onset of exposure. The induced miRNAs were profiled using miRNA microarrays, and the analysis of the data was performed using the miRWalk 2.0 and DAVID bioinformatics tools. DOX induced early deregulation of 14 miRNAs (10 up-regulated and 4 down-regulated) and persistent up-regulation of 5 miRNAs during drug washout. Computational miRNA gene target predictions suggested that several DOX-responsive miRNAs might regulate the mRNA expression of genes involved in cardiac contractile function. The hiPSC-CMs exposed to DOX in a range from 39 to 156 nM did not show a significant release of the cytotoxicity marker lactate dehydrogenase (LDH) compared to controls. Quantitative real-time PCR analyses confirmed the early deregulation of miR-187-3p, miR-182-5p, miR-486-3p, miR-486-5p, miR-34a-3p, miR 4423-3p, miR-34c-3p, miR-34c-5p and miR-1303, and also the prolonged up regulation of miR-182-5p, miR-4423-3p and miR-34c-5p. Thus, we identified and validated miRNAs showing differential DOX-responsive expression before the occurrence of cytotoxicity markers such as LDH, and these miRNAs also demonstrated the significant involvement in heart failure in patients and animal models. These results suggest that the DOX-induced deregulated miRNAs in human CMs may be used as early sensitive cardiotoxicity biomarkers for screening potential drugs and environmental cardiotoxicants with a similar mechanism of action. PMID- 26842499 TI - The tomato floral homeotic protein FBP1-like gene, SlGLO1, plays key roles in petal and stamen development. AB - MADS-box transcription factors play important role in plant growth and development, especially floral organ identities. In our study, a MADS-box gene SlGLO1- tomato floral homeotic protein FBP1-like gene was isolated. Its tissue specific expression profile analysis showed that SlGLO1 was highly expressed in petals and stamens. RNAi (RNA interference) repression of SlGLO1 resulted in floral organ abnormal phenotypes, including green petals with shorter size, and aberrant carpelloid stamens. SlGLO1-silenced lines are male sterile. Total chlorophyll content was increased and chlorophyll biosynthetic genes were significantly up-regulated in SlGLO1-silenced petals and stamens. Furthermore, B class genes expression analysis indicated that the repressed function of SlGLO1 led to the enhanced expression of TAP3 and the down-regulation of TPI in the petals and stamens, while the expression of TM6 was reduced in petals and increased in stamens and carpels of SlGLO1-RNAi plants. Additionally, pollen grains of transgenic lines were aberrant and failed to germinate and tomato pollen-specific genes were down-regulated by more than 90% in SlGLO1-silenced lines. These results suggest that SlGLO1 plays important role in regulating plant floral organ and pollen development in tomato. PMID- 26842501 TI - Non-typeable Haemophilus influenzae purulent pericarditis in a child with cystic fibrosis. AB - Early airway colonization and infection with Haemophilus influenzae in children with cystic fibrosis (CF) is common. Although the pathogenicity of non-typeable H. influenzae (NTHi) in patients with CF is controversial, this organism can cause both upper and lower respiratory tract infections. Extra-pulmonary disease, however, is rare. Purulent pericarditis is a suppurative complication of bacterial infection of the pericardial space that can arise as a result of direct extension from an adjacent infection. We describe a case of purulent pericarditis due to NTHi in a young child with CF that developed as a complication of inadequately treated bronchopneumonia. PMID- 26842500 TI - Can the general public use vignettes to discriminate between Alzheimer's disease health states? AB - BACKGROUND: Valid estimates of health-related quality-of-life (HRQoL) are often difficult to obtain from persons with Alzheimer's disease (AD) and family caregiver proxies. To help assess whether the general public can serve as an alternate source of proxy HRQoL estimates in AD, we examined whether the general public can use vignettes to discriminate between AD health states. METHODS: We administered a telephone survey to randomly recruited participants from the general public who were aged 18 years or older. Interviewers read vignettes describing the mild, moderate, and severe AD health states to the participants, who answered the EQ-5D-5L and Quality of Life-Alzheimer's Disease (QoL-AD) scales as if they had AD based on the vignette descriptions. Participants also answered the EQ-5D-5L for their current health states. We converted EQ-5D-5L responses into health utility scores using Canadian preference weights. We employed the Wilcoxon signed rank test to examine whether mean health utility scores and mean QoL-AD scores differed between health states. We used Pearson's r to assess correlations between health utility and QoL-AD scores. RESULTS: Forty-eight participants (median age = 53 years; 25 female) completed the telephone interview; health utility and QoL-AD scores decreased as AD severity increased (p <0.0001). Mean health utility scores were 0.65 (mild), 0.51 (moderate), and 0.25 (severe). Mean QoL-AD scores were 26.7 (mild), 23.0 (moderate), and 17.4 (severe). The correlations between health utility and QoL-AD scores were moderate to strong (r >= 0.62). CONCLUSIONS: Using the vignettes, the general public provided HRQoL estimates that discriminated between the three AD health states. This finding suggests the general public may be a promising source of proxy HRQoL estimates in place of persons with AD. PMID- 26842502 TI - Supporting Physical Activity in the Childcare Environment (SPACE): rationale and study protocol for a cluster randomized controlled trial. AB - BACKGROUND: Young children are prone to low levels of physical activity in childcare. Researchers have identified that preschoolers tend to be more active outdoors than indoors, with higher activity levels occurring during the first 10 minutes of outdoor playtime. Additionally, interventions incorporating either staff training or the inclusion of play equipment have been effective at increasing children's activity in this setting. As such, the overarching objective of the Supporting Physical Activity in the Childcare Environment (SPACE) intervention is to improve the physical activity levels of preschoolers during childcare hours, utilizing a combination of the above components. The purpose of this manuscript is to provide a detailed account of the protocol, innovative methods, and evaluation plans used in the implementation of the SPACE study; in an effort to support the development of further research in this field. METHODS/DESIGN: The SPACE study, a cluster randomized controlled trial, involves 22 childcare centres randomly allocated to either the experimental (n = 11) or the control (n = 11) group. Childcare centres receiving the intervention will adopt an 8-week physical activity intervention with the following components: 1. shorter, more frequent bouts of outdoor playtime (4 * 30 min periods rather than 2 * 60 min periods); 2. new portable play equipment (e.g., obstacle course, balls); and, 3. staff training (1 * 4 hr workshop). Actical accelerometers will be used to assess total physical activity with measurements taken at baseline (i.e., week 0), immediately post-intervention (i.e., week 8), and at 6- and 12 month follow-up. As secondary objectives, we aim to evaluate the effectiveness of the intervention on preschoolers': a) sedentary time; b) standardized body mass index scores (percentiles); c) health-related quality of life; and childcare providers' physical activity-related knowledge and self-efficacy to implement physical activity. DISCUSSION: The SPACE study aims to increase the low levels of physical activity observed within childcare centres. The findings of this work may be useful to policy makers and childcare providers to consider modifications to the current childcare curriculum and associated outdoor play time. TRIAL REGISTRATION: ISRCTN70604107 (October 8, 2014). PMID- 26842511 TI - Knowledge and perceptions of risk for cardiovascular disease: Findings of a qualitative investigation from a low-income peri-urban community in the Western Cape, South Africa. AB - BACKGROUND: South Africa currently faces an increasing burden of cardiovascular disease. Although referred to clinics after community screening initiatives, few individuals who are identified to be at high risk for developing cardiovascular disease attend. Low health literacy and risk perception have been identified as possible causes. We investigated the knowledge and perceptions about risk for cardiovascular disease in a community. METHOD: We conducted a series of focus group discussions with individuals from a low incomeperi-urban community in the Western Cape, South Africa. Different methods of presenting risk were explored. The data were organised into themes and analysed to find associations between themes to provide explanations for our findings. RESULTS: Respondents' knowledge of cardiovascular disease and its risk factors varied, but most were familiar with the terms used to describe cardiovascular disease. In contrast, understanding of the concept of risk was poor. Risk was perceived as a binary concept and evaluation of different narrative and visual methods of presenting risk was not possible. CONCLUSION: Understanding cardiovascular disease and its risk factors requires a different set of skills from that needed to understand uncertainty and risk. The former requires knowledge of facts, whereas understanding of risk requires numerical and computational skills. Without a better understanding of risk, risk assessments for cardiovascular disease may fail in this community. PMID- 26842512 TI - Prevalence and associated risk factors of hypertension amongst adults in a rural community of Limpopo Province, South Africa. AB - BACKGROUND: Hypertension is problem already faced by urban populations of South Africa, but little is known about its prevalence and risk factors in rural areas. AIM: To assess the prevalence of and risk factors associated with hypertension amongst adults in a rural community in South Africa. SETTING: Dikgale Health and Demographic Surveillance Site, Limpopo Province, South Africa. METHODS: A community-based cross-sectional survey was carried out at this site where individuals aged 15 years and older were screened using a locally adapted version of the World Health Organization STEPwise questionnaire. Demographics, anthropometry and three independent blood pressure (BP) readings were taken. The average of the three BP measurements was used in analysis, and hypertension taken as systolic and diastolic BP of >= 140 or >= 90 mmHg respectively, or at least a two-week history of antihypertensive treatment. Analysis included the Chi-square test and statistical significance was set at p <= 0.05. RESULTS: A total of 1407 individuals were interviewed, of whom 1281 had complete BP, weight and height measurements taken. The mean age of participants was 44.2 +/- 2 0.9 years (range 15-98 years), 63% were female, 55% were single and 90% were unemployed, whilst 13% were tobacco smokers and 20% reported drinking alcohol. Overall prevalence of hypertension was 41% and this was significantly associated with age and marital status. CONCLUSION: The prevalence of hypertension was found to be high. Prevention strategies are urgently needed to address this life-threatening and important risk factor for cardiovascular disease in rural Limpopo Province. PMID- 26842513 TI - Two-year longitudinal health-related fitness, anthropometry and body composition status amongst adolescents in Tlokwe Municipality: The PAHL Study. AB - AIM: To evaluate a two-year longitudinal development of health-related fitness, anthropometry and body composition status amongst adolescents in Tlokwe Municipality, Potchefstroom, South Africa. SETTING: A total of 283 high-school learners (111 boys and 172 girls) of ages 14 and 15 years who were part of the ongoing Physical Activity and Health Longitudinal Study (PAHLS) participated in the study. For the purpose of the present study, data collected for 2011 and 2012 for anthropometric, body composition and health-related physical fitness were used. RESULTS: Body mass index (BMI) classification of boys and girls for 2011 and 2012 showed that 24.3% of them were underweight compared with 21% in 2012. In 2011, 50% of boys and girls had normal bodyweight compared with 52% in 2012, whilst 25.5% of the total group of participants were overweight compared with 27% in 2012. Both boys and girls showed significant increases of 5.9% in body fat (BF) and 3.2 kg in body weight over two years' measurements, respectively. Regarding health-related fitness (i.e BAH), boys showed an increase of 14.8 seconds whilst girls gained 9.6 seconds. Significant decreases were found for sit ups in both boys and girls. A significant VO2max increase of 2.9 mL/kg/min. was found in boys over the time period. A non-significant decrease of -0.5 mL/kg/min. was observed in girls. Regression coefficients showed that changes in BMI were inversely associated with those in health-related physical fitness. The changes in percentage BF were negatively associated with standing broad jump (SBJ), bent arm hang (BAH) and VO2 max in both boys and girls. A low significant positive association was found between changes in waist-to-height ratio (WHtR) and SBJ in both genders, whilst inverse low associations were found between WHtR and BAH in girls and for VO2max in both genders. CONCLUSION: Changes in BMI, %BF and WHtR were negatively associated with strength and running performances in the participating children. The relative increase in overweight, especially in girls, negatively affected their endurance running and static strength performances. The health implications of the observed findings are discussed and recommendations offered for physical activity intervention in school physical education (PE) programmes. PMID- 26842514 TI - Why are babies born before arrival at health facilities in King Sabata Dalindyebo Local Municipality, Eastern Cape, South Africa? A qualitative study. AB - INTRODUCTION: Babies born before arrival at a health facility have a higher risk of neonatal death and their mothers a higher risk of maternal death compared with those born in-facility. The study explored the reasons for mothers giving birth before arrival (BBA) at health facilities and their experiences of BBA. METHODS: A qualitative research design was used. Individual and focus group interviews of BBA mothers and of nurses were undertaken at a community health centre and a district hospital in King Sabata Dalindyebo Local Municipality. RESULTS: Reasons for BBA included a lack of transport, a lack of security at night that deterred mothers from travelling, precipitate labour, failure to identify true labour, and a lack of waiting areas at health facilities. Traditional and cultural beliefs favouring childbirth at homeand nurses' negative attitudes during antenatal care and labour influenced mothers to go to health facilities when in advanced labour. Mothers were aware of possible complications associated with BBA. CONCLUSION: Socio-economic, individual, cultural and health system factors influence the occurrence of BBA. Relevant parties need to address these factors to ensure that all babies in the King Sabata Dalindyebo Local Municipality are delivered within designated health facilities. PMID- 26842515 TI - Prevalence of and factors influencing postnatal depression in a rural community in South Africa. AB - BACKGROUND: Knowledge about postnatal depression (PND) and associated risk factors which influence the development of PND is vital for early detection, intervention and prevention. SETTING: The study was conducted in primary health care clinics (PHC) in the Witzenberg subdistrict, a rural community in South Africa. OBJECTIVES: Objectives of this study were to determine the prevalence of PND and to identify the contributing risk factors associated with PND. METHODS: A descriptive cross sectional research design with a quantitative approach was applied. The target population was mothers, 18 years and older. A convenience sampling method was used to select a sample of 159 (10%) from a population of 1605 live births. The Edinburgh Postnatal Depression Scale (EPDS) and Beck Depression Inventory (BDI), two validated self-rating questionnaires, including a questionnaire based on demographical, psychosocial and obstetrical data, were applied. The data was analysed using various statistical tests to determine statistical associations between variables using a 95% confidence interval. RESULTS: PND was a serious health problem with 50.3% of the mothers who suffered from PND. A BDI analysis showed that of the participants who had PND, 28.8% was severe, 48.8% moderate and 22.5% mild. Factors influencing the development of PND included most participants (63.5%) were unmarried, 61.3% were unemployed and the majority (53.8%) had a history of a psychiatric illness. Significant associations between PND and unplanned and unwelcome babies (p < 0.01); partner relationship (p < 0.01); were identified. CONCLUSION: Prevention, early detection, appropriate referral and treatment of PND are critical in managing maternal, child and family well-being. PMID- 26842516 TI - Understanding the organisational culture of district health services: Mahalapye and Ngamiland health districts of Botswana. AB - BACKGROUND: Botswana has a shortage of health care workers, especially in primary healthcare. Retention and high performance of employees are closely linked to job satisfaction and motivation, which are both highest where employees' personal values and goals are realised. AIM: The aim of the study was to evaluate employees' personal values, and the current and desired organisational culture of the district health services as experienced by the primary health care workers. SETTING: The study was conducted in the Ngamiland and Mahalapye health districts. METHOD: This was a cross sectional survey. The participants were asked to select 10 values that best described their personal, current organisational and desired organisational values from a predetermined list. RESULTS: Sixty and 67 health care workers completed the survey in Mahalapye and Ngamiland districts, respectively. The top 10 prevalent organisational values experienced in both districts were: teamwork, patient satisfaction, blame, confusion, job insecurity, not sharing information and manipulation. When all the current values were assessed, 32% (Mahalapye) and 36% (Ngamiland) selected by health care workers were potentially limiting organisational effectiveness. The organisational values desired by health care workers in both districts were: transparency, professional growth, staff recognition, shared decision-making, accountability, productivity, leadership development and teamwork. CONCLUSIONS: The experience of the primary health care workers in the two health districts were overwhelmingly negative, which is likely to contribute to low levels of motivation, job satisfaction, productivity and high attrition rates. There is therefore urgent need for organisational transformation with a focus on staff experience and leadership development. PMID- 26842517 TI - Pain management in patients with long-bone fractures in a district hospital in KwaZulu-Natal, South Africa. AB - BACKGROUND: This study reviewed pain severity and assessment as recalled by patients with longbone fractures. The focus was on the intervals between admission, pain assessment and analgesic provision, as delay of analgesia for acute pain can result in complex chronic pain syndromes. AIM: The aims were to explore patients' recollection of pain severity and assessment in an emergency department (ED) and whether analgesia prescribed in the ED correlated with pain severity.' SETTING: The study site was a district hospital ED in KwaZulu-Natal, South Africa. METHODS: This exploratory study considered aspects of pain in adults with long-bone fracture who were admitted to an ED and later referred to an orthopaedic unit. Data collection took place in the orthopaedic unit where participants were requested to recall their pain severity (using a visual analogue scale) whilst in the ED. RESULTS: Ninety-three patients participated, most of whom were African males. Over 60% recalled their pain severity in the ED as 5 or greater on a visual analogue perception scale. No formal tool was used to assess or record pain in the ED, and there was no association between recalled pain severity and type of analgesia prescribed. CONCLUSION: The majority of patients were assessed for pain in the ED. Analgesia given to most patients was inadequate for the degree of pain they experienced. A pain assessment protocol should be developed for doctors and nurses to serve as a guideline in assessing patients with long-bone fractures and prescribing appropriate analgesia. PMID- 26842518 TI - The expected and actual communication of health care workers during the management of intrapartum: An interpretive multiple case study. AB - BACKGROUND: Daily activities within a health care organisation are mediated by information communication processes (ICP) involving multiple health care professionals at different levels of care. Effective perinatal management requires critical information to be accurately communicated. If there is a breakdown in this communication patient safety is at risk for various reasons such as: inadequate critical information, misconception of information and uninformed decisions being made. The purpose of this study was to interpret the complexities around ICP in order to contribute to the effective management of the intrapartum period. METHODS: Multi method, multiple case study approach was used to understand the ICP during the management of the intrapartum period. During the study, the expected ICP, the actual ICP, the challenges involved and the desired ICP were analysed. Twenty-four in-depth interviews with skilled birth attendants (SBAs) employing observer-as-participant roles, field notes, and document review methods were utilised to gather the data. Thematic analysis was utilised to analyse the data using Atlas TI software. RESULTS: The study revealed three subthemes which emerged from the expected ICP, whilst three others that emerged formed the theme actual ICP. The subthemes from the expected ICP included: accessibility of obstetric services, expected referral, recommended tools, expected communication and expected documentation. The theme actual ICP held three emerging subthemes: the handover processes, collaborative information seeking, information communicated and referral processes. CONCLUSION: This study showed that what was expected was not what was actually happening. The requirements of the policies and protocols need to be effectively implemented to improve practice building these into current biomedical guidelines. PMID- 26842519 TI - Intestinal helminth infections amongst HIV-infected adults in Mthatha General Hospital, South Africa. AB - BACKGROUND: In South Africa, studies on the prevalence of intestinal helminth co infection amongst HIV-infected patients as well as possible interactions between these two infection sare limited. AIM: To investigate the prevalence of intestinal helminth infestation amongst adults living with HIV or AIDS at Mthatha General Hospital. SETTING: Study participants were recruited at the outpatient department of Mthatha General Hospital, Mthatha, South Africa. METHODS: This cross-sectional study was conducted between October and December 2013 amongst consecutive consenting HIV-positive adult patients. Socio-demographic and clinical information were obtained using data collection forms and structured interviews. Stool samples were collected to investigate the presence of helminths whilst blood samples were obtained for the measurement of CD4+ T-cell count and viral load. RESULTS: Data were obtained on 231 participants, with a mean age of 34.9 years, a mean CD4 count of 348 cells/MUL and a mean viral load of 4.8 log10 copies/mL. Intestinal helminth prevalence was 24.7%, with Ascaris Lumbricoides (42.1%) the most prevalent identified species. Statistically significant association was found between CD4 count of less than 200 cells/ MULand helminth infection (p = 0.05). No statistically significant association was found between intestinal helminth infection and the mean CD4 count (p = 0.79) or the mean viral load (p = 0.98). CONCLUSION: A high prevalence of intestinal helminth infections was observed amongst the study population. Therefore, screening and treatment of helminths should be considered as part of the management of HIV and AIDS in primary health care. PMID- 26842520 TI - Experiences of general practitioners in the Ga-Rankuwa and Mabopane areas in dealing with patients who have sexual problems. AB - BACKGROUND: Sexual problems are common. Many patients with sexual health dysfunction use self-help literature or are often managed in general practice. However, many general practitioners (GPs) find it difficult to discuss sexual health issues because they feel uncomfortable with this and lack training in these matters. These GPs are now referring patients with sexual dysfunction to specialists. AIM: We sought to explore how GPs working in the Mabopane and Ga Rankuwa areas of handle sexual problems of their patients. SETTING: The setting was the Mabopane and Ga-Rankuwa areas of North-West Tshwane, in Gauteng Province. METHODS: A qualitative study comprising eight free attitude interviews with purposefully selected four male and four female GPs. All interviews were conducted in English and tape-recorded. Field notes in the form of a detailed diary was kept. The tapes were transcribed verbatim, and the transcriptions were checked against the tapes for omissions and inaccuracies. RESULTS: Six themes emerged from the interviews: causes of sexual problems; presentation of sexual problems to the doctor; management of sexual health problems; sex is a taboo topic; society's need for sexual health discussions, and these discussions have already begun; previous limited exposure and training, and a need for more sexual health training. CONCLUSION: This study confirms earlier findings that patients could be either reluctant to discuss their problems or are open about them when presenting to doctors with sexual dysfunction. GPs were not exposed to sexual health training at medical school and, because of this shortcoming, felt that training in sexual medicine should be part of the curriculum. PMID- 26842522 TI - Hypertension in rural communities in Delta State, Nigeria: Prevalence, risk factors and barriers to health care. AB - INTRODUCTION: Hypertension is a global health challenge and its prevalence is increasing rapidly amongst adults in many African countries. Some studies on the prevalence and risk factors of hypertension have been conducted in Nigeria, but none within Delta State. We assessed the prevalence of hypertension and associated risk factors amongst adults in three villages in the Ibusa community in Delta State, Nigeria. METHOD: Homesteads were randomly selected and all consenting adults (>= 18 years of age) were recruited for this cross-sectional study (134 individuals: 48 men, 86 women). Sociodemographic data and anthropometric measurements (weight, height and abdominal circumference) were recorded. Diagnosis of hypertension was based on blood pressure >= 140/90 mmHg. RESULT: Hypertension prevalence in this rural community was 44%. Results from one village (Ogboli: 82%) and ethnic group (Ibo: 50%) were significantly higher than in others in the same variable category. Multivariate logistic regression analysis suggested increasing age, increasing body mass index and high salt intake as prominent risk factors for hypertension. Lack of funds and equipment shortage in clinics were most often reported as barriers to healthcare. CONCLUSION: A nutritional education programme to promote low-cholesterol and low salt diets is recommended to specifically target people in higher-risk areas and of higher-risk ethnicity. Local barriers to accessing health care need to be addressed. PMID- 26842521 TI - Prevalence and causes of visual impairment in patients seen at Nkhensani Hospital Eye Clinic, South Africa. AB - BACKGROUND: Knowledge of the prevalence and causes of visual impairment (VI) amongst hospital patients is useful in planning preventive programmes and provision of eye-care services for residents in the surrounding communities. AIM: The aim of this study was to determine the prevalence and causes of VI amongst eye clinic patients at Nkhensani Hospital. The relationship between VI and age was also investigated. SETTING: Nkhensani Hospital in the Greater Giyani subdistrict municipality, Mopani district, Limpopo Province, South Africa. METHODS: Four hundred participants aged 6-92 years were selected for the study using a convenient sampling method. Presenting and best corrected visual acuities (VA) were measured with a LogMAR E chart. Presenting VA (PVA) in the right and left eyes and in the better eye of the patients was used to determine the prevalence of VI, low vision (LV) and blindness. Ophthalmoscope was used to diagnose the eye conditions causing VI amongst participants. RESULTS: The prevalence of VI based on the PVA in the right eye was 34.8% and in the left eye, the prevalence was 35.8%. There was a significant association between age of the participants and VI in the right and left eyes (p = 0.00) in each case, respectively. Based on the vision in the better eye of each patient, the prevalence of VI was 28.0% and there was a significant association between VI and age of the participants (p = 0.00). The main causes of VI were uncorrected refractive errors, cataract and glaucoma. CONCLUSION: Findings in this study indicate that a large proportion of VI is preventable. Focusing on refractive error correction and surgical intervention for cataract would significantly reduce the burden of VI amongst patients utilising this hospital. PMID- 26842523 TI - Knowledge of community care workers about key family practices in a rural community in South Africa. AB - BACKGROUND: Interventions by community care workers within the context of community-based integrated management of childhood illness (CIMCI) may have a positive effect on child health if the health workers have adequate knowledge about key family practices. SETTING: The study was conducted in rural areas of the West Coast district in the Western Cape, South Africa. OBJECTIVES: The objective of this study was to determine the knowledge of community care workers about five of the 16 key family practices of CIMCI. METHODS: A descriptive survey collected a self-administered questionnaire from 257 community care workers out of a possible total of 270 (95.2% response rate). Descriptive and inferential statistical analysis was applied. RESULTS: Only 25 of the respondents (10%) obtained a score higher than 70% on the knowledge-based items of the questionnaire. Less than 25% of respondents answered questions in these key areas correctly (pneumonia [17%], tuberculosis [13%], HIV/AIDS [9%] immunisation [3%] and recommendations for a child with fever [21%]). Statistically significant correlations were found between the total score a respondent achieved and the highest level of education obtained (p < 0.01), the level of in-service training (p < 0.01), attendance of a CIMCI five-day training course (p < 0.01), and completing a subsequent refresher course (p < 0.01). CONCLUSION: The knowledge of CCWs was inadequate to provide safe, quality CIMCI. CIMCI refresher courses should be offered annually to improve CCWs' knowledge and the quality of care that they render. Regular update courses could contribute to building competence. PMID- 26842524 TI - Exploring the meaning of caring amongst student midwives, professional midwives and educators in Tshwane, South Africa. AB - BACKGROUND: In spite of caring being the core of midwifery and nursing, there is a constant public outcry about uncaring behaviours of midwives towards clients. Local media reports and recent discussion in the health system have highlighted the concerns regarding caring behaviours of midwives. Thus, there is a need to compare the meaning of caring from the perspectives of student midwives, midwives and educators. AIMS: The aim of this article was to determine the meaning of caring from the perspectives of the undergraduate student midwives, the professional midwives, and the educators teaching midwifery in Tshwane. SETTING: The study was conducted at healthcare institutions which the undergraduate student midwives attended for work integrated learning and at nursing education institutions in Tshwane, South Africa. METHODS: The strategy was qualitative and exploratory in nature. The population comprised student midwives, professional midwives and educators. Purposive sampling was done. Focus group discussions were held with student midwives and professional midwives, whilst the naive sketch form was used as data-collection instrument for educators. Content data analysis was done. The total sample realised was 38. RESULTS: The findings revealed that 'caring' was taken to mean being well conversant, up to-date and proficient in the field of work as well as considerate and respectful to others. The professional midwives indicated that they have seen colleagues demonstrate uncaring behaviour whilst educators emphasised respect as caring. CONCLUSION: The student midwives, professional midwives and educators described caring as being a competent nurse with compassion and respect for others. PMID- 26842527 TI - Developing family medicine in Zambia. PMID- 26842525 TI - Does counselling improve uptake of long-term and permanent contraceptive methods in a high HIV-prevalence setting? AB - BACKGROUND: Studies have shown a reduced uptake of contraceptive methods in HIV positive women of childbearing age, mainly because of unmet needs that may be a result of poor promotion of available methods of contraception, especially long term and permanent methods (LTPM). AIM: To compare the uptake of contraceptive methods, and particularly LTPM, by HIV-positive and HIV negative post-partum mothers, and to assess the effects of counselling on contraceptive choices. SETTING: Three government district hospitals in Swaziland. METHODS: Interviews were conducted using a structured questionnaire, before and after counselling HIV negativeand HIV-positive post-partum women in LTPM use, unintended pregnancy rates, future fertility and reasons for contraceptive choices. RESULTS: A total of 711 women, of whom half were HIV-positive, participated in the study. Most (72.3% HIV-negative and 84% HIV-positive) were on modern methods of contraception, with the majority using 2-monthly and 3-monthly injectables. Intended use of any contraceptive increased to 99% after counselling. LTPM use was 7.0% in HIV-negative mothers and 15.3% in HIV-positive mothers before counselling, compared with 41.3% and 42.4% in HIV-negative and HIV-positive mothers, respectively, after counselling. Pregnancy intentions and counselling on future fertility were significantly associated with current use of contraception, whilst current LTPM use and level of education were significantly associated with LTPM post-counselling. CONCLUSION: Counselling on all methods including LTPM reduced unmet needs in contraception in HIV positive and HIV-negative mothers and could improve contraceptive uptake and reduce unintended pregnancies. Health workers do not always remember to include LTPM when they counsel clients, which could result in a low uptake of these methods. Further experimental studies should be conducted to validate these results. PMID- 26842528 TI - Utilization of supportive care by survivors of colorectal cancer: results from the PROFILES registry. AB - PURPOSE: In an equitable healthcare system, healthcare utilization should be predominantly explained by patient-perceived need and clinical need factors. This study aims to analyze whether predisposing, enabling, and need factors are associated with the utilization of supportive care (i.e., dietary care, oncological nursing care, physical therapy, psychological care, or participation in a rehabilitation program consisting of an exercise component and a psycho educational component) among survivors of colorectal cancer in the Netherlands. METHODS: Cross-sectional data of 3957 survivors of colorectal cancer (1-11 years after diagnosis) were used. Clinical data from the Eindhoven Cancer Registry were linked to questionnaire data from the PROFILES registry. Regression analyses were used to examine which predisposing, enabling, and need factors were associated with self-reported utilization of supportive care. RESULTS: Utilization of supportive care was primarily associated with younger age, patient-perceived need (i.e., lower physical health, anxious mood, depressive mood, and fatigue), and clinical need (i.e., tumor stage, radiotherapy, chemotherapy, comorbidity, having a stoma and lower BMI) factors. CONCLUSIONS: In the Netherlands, utilization of supportive care by survivors of colorectal cancer is primarily associated with younger age, patient-perceived need, and clinical need factors. Apart from the association with younger age, the utilization of supportive care services seems to be quite equitable. Further research is needed to determine whether there is indeed inequity in the provision of supportive care to older survivors, or whether older survivors are less in need of supportive care. PMID- 26842531 TI - Snare-Facilitated Retrieval of Entangled Impella Device. PMID- 26842529 TI - Association between drug intake and incidence of malignancies in patients with Juvenile Idiopathic Arthritis: a nested case-control study. AB - BACKGROUND: Several medications for treatment of Juvenile Idiopathic Arthritis (JIA) are considered to be carcinogenic. Therefore, the aim was to assess whether there is an association between therapeutic interventions and malignancies in JIA patients. FINDINGS: A nested case-control study was carried out within a retrospective cohort study of 3698 JIA patients diagnosed between 1952 and 2010. All 48 JIA patients with a diagnosis of a malignant tumour and up to four matched controls for each received a questionnaire about their use of medication. Subsequently treatment was compared between cases and controls and analyses performed for 37 cases and 125 controls (response 88.5 %). Treatment with DMARD (84 %) was most frequently used, followed by glucocorticoids (66 %) and immunosuppressives (65 %). Twenty percent reported to have ever been taking biologics. Medication use did not differ significantly between cases and controls. CONCLUSIONS: Our results did not show an association between medications used and malignancies in JIA patients. PMID- 26842530 TI - Prevention of age-induced N(epsilon)-(carboxymethyl)lysine accumulation in the microvasculature. AB - OBJECTIVE: N(epsilon)-(carboxymethyl)lysine (CML) is one of the major advanced glycation end products in both diabetics and nondiabetics. CML depositions in the microvasculature have recently been linked to the aetiology of acute myocardial infarction and cognitive impairment in Alzheimer's disease, possibly related to local enhancement of inflammation and oxidative processes. We hypothesized that CML deposition in the microvasculature of the heart and brain is age-induced and that it could be inhibited by a diet intervention with docosahexaenoic acid (DHA), an omega-3 fatty acid known for its anti-inflammatory and antioxidative actions. MATERIALS AND METHODS: ApoE(-/-) mice (n = 50) were fed a Western diet and were sacrificed after 40, 70 and 90 weeks. Part of these mice (n = 20) were fed a Western diet enriched with DHA from 40 weeks on. CML in cardiac and cerebral microvessels was quantified using immunohistochemistry. RESULTS: Cardiac microvascular depositions of CML significantly increased with an immunohistochemical score of 11.85 [5.92-14.60] at 40 weeks, to 33.17 [17.60 47.15] at 70 weeks (P = 0.005). At the same time points, cerebral microvascular CML increased from 6.45; [4.78-7.30] to 12.99; [9.85-20.122] (P = 0.003). DHA decreased CML in the intramyocardial vasculature at both 70 and 90 weeks, significant at 70 weeks [33.17; (17.60-47.15) vs. 14.73; (4.44-28.16) P = 0.037]. No such effects were found in the brain. CONCLUSIONS: Accumulation of N(epsilon) (carboxymethyl)lysine in the cerebral and cardiac microvasculature is age-induced and is prevented by DHA in the intramyocardial vessels of ApoE(-/-) mice. PMID- 26842533 TI - Academic Excellence Ignites Leadership Potential. PMID- 26842532 TI - Early Initiation of Everolimus After Liver Transplantation: A Single-Center Experience. AB - BACKGROUND: Evidence relating to early everolimus use after liver transplantation remains limited. MATERIAL AND METHODS: Ninety-one adult patients undergoing liver transplantation at our center during 2007-2012 in whom everolimus therapy was initiated <3 months post-transplant were analyzed retrospectively. Everolimus was started on days 1-5 in 50 patients (group 1) and after day 5 in 41 patients (group 2). Most patients continued to receive low-dose cyclosporine (59.3%, target 50-80 ng/ml) or low-dose tacrolimus (25.3%; target 3-5 ng/ml). Mean follow up was 4.6 years. RESULTS: One-, three- and five-year patient survival rates were 80.5%, 74.2%, and 70.5%, respectively, and did not differ between groups 1 and 2. Six patients (6.6%) developed biopsy-proven acute rejection after a median of 47 days (range 27-356 days). Everolimus was discontinued due to adverse events in 21 patients (23.1%). Incisional hernia repair occurred in 14.0% and 9.4% of patients in group 1 and 2, respectively. Renal function remained stable during follow-up, despite poor baseline function. CONCLUSIONS: Everolimus with very low-dose calcineurin inhibitor given immediately after liver transplantation appears safe and effective, achieving a low rejection rate with well-preserved renal function. PMID- 26842534 TI - Staphylococcal Scalded Skin Syndrome: A Case Review. AB - Staphylococcal scalded skin syndrome (SSSS) is a rare yet well-known exfoliative skin syndrome. It involves extensive desquamated areas caused by an exfoliative toxin from Staphylococcus aureus. The typical presentation of SSSS allows for early diagnosis and treatment of the disease. Knowing and understanding the prevalence, pathophysiology, risk factors, and diagnosis of SSSS will ensure that infants being treated and cared for by neonatal nurses and neonatal nurse practitioners will receive appropriate, comprehensive, and multidisciplinary care while in the NICU. The purpose of this case review is to inform neonatal nurses and practitioners of the current literature that focuses on the diagnosis and management of SSSS. PMID- 26842535 TI - Septo-Optic Dysplasia: A Case Study. AB - Septo-optic dysplasia (SOD) is a rare congenital heterogeneous malformation. SOD was formerly known as de Morsier syndrome, which associated a midline brain defect such as an absent septum pellucidum with optic nerve hypoplasia. The diagnosis of SOD is made when there are two or more characteristics of the classic triad. The triad consists of optic nerve hypoplasia, pituitary hormone abnormalities, and midline brain defects, although it can vary in the severity of clinical presentation and phenotype. The purpose of this article is to review a case and analyze the literature regarding prevalence, etiology, clinical presentation, diagnosis, and management of SOD. PMID- 26842536 TI - Management of Epidermolytic Ichthyosis in the Newborn. AB - Epidermolytic ichthyosis (EI) is a rare autosomal dominant genodermatosis that presents at birth as a bullous disease, followed by a lifelong ichthyotic skin disorder. Essentially, it is a defective keratinization caused by mutations of keratin 1 (KRT1) or keratin 10 (KRT10) genes, which lead to skin fragility, blistering, and eventually hyperkeratosis. Successful management of EI in the newborn period can be achieved through a thoughtful, directed, and interdisciplinary or multidisciplinary approach that encompasses family support. This condition requires meticulous care to avoid associated morbidities such as infection and dehydration. A better understanding of the disrupted barrier protection of the skin in these patients provides a basis for management with daily bathing, liberal emollients, pain control, and proper nutrition as the mainstays of treatment. In addition, this case presentation will include discussions on the pathophysiology, complications, differential diagnosis, and psychosocial and ethical issues. PMID- 26842537 TI - Trisomy 13: Changing Perspectives. AB - The diagnosis of trisomy 13 has been considered incompatible with life. Trisomy 13 is associated with a pattern of congenital anomalies and mental disabilities that make caring for these infants a challenge for both the family and health care professionals. The clinical management of trisomy 13 varies based on the organ systems involved. The current standard of care has been withholding intensive support and providing comfort care. Recent literature suggests there are improved outcomes in infants who receive intensive care at birth. In addition, case reports evaluating older children with trisomy 13 report that, although there are significant intellectual and psychomotor disabilities, these children do meet developmental milestones such as smiling in response to parents, sitting unassisted, and walking with a walker. This case review will include a discussion of the clinical course of an infant born with mosaic trisomy 13 where the parents requested intensive care. PMID- 26842538 TI - Early Blood Transfusion and Resolution of Disseminated Intravascular Coagulation Associated with Massive Subgaleal Hemorrhage. AB - A male infant delivered to a primipara woman following vacuum applications. He was vigorous at birth, with small caput and scalp bruising. His head was enlarging; he became pale with respiratory distress. Subgaleal hemorrhage (SGH) was suspected. His hematocrit was noted to be 26.2 percent prior to transfusion of O, Rh-negative blood (40 mL/kg). Moderate disseminated intravascular coagulation (DIC) was noted at 12 hours of age. Posttransfusion of fresh frozen plasma (FFP), his condition became stable, and DIC gradually resolved. Head magnetic resonance imaging did not show intracranial hemorrhage. Although one episode of seizures was noted, electroencephalogram was normal. With the application of obstetric vacuum, we recommend that the neonatal health care professionals frequently evaluate the infant's condition. In light of developing fluctuant subgaleal fluid associated with pallor, anemia, metabolic acidosis, and respiratory distress, immediate blood transfusion is warranted. In the presence of DIC, transfusion of FFP is beneficial. PMID- 26842540 TI - Supporting Parents with Mental Health Support in the NICU. AB - Parents of premature babies are at high risk for postpartum depression and Posttraumatic stress disorder and need a lot of mental health support. Enter Parijat Deshpande, a mother who gave birth to her son in the 24th week and has a background in psychology and is now a health and wellness counselor. Parijat has a strong focus on perinatal wellness and helping parents of a preemie reduce their stress and increase the parent-child bond. PMID- 26842541 TI - News of the Academy of Neonatal Nursing. PMID- 26842543 TI - Air-abrasive debridement with glycine powder versus manual debridement and chlorhexidine administration for the maintenance of peri-implant health status: a six-month randomized clinical trial. AB - STUDY DESIGN: This single-masked, randomized and six-month clinical intervention trial including two study groups was planned to evaluate the efficacy of maintenance treatment with glycine powder on the periodontal health of peri implant tissues. METHODS: A total of 46 patients with partial or total edentulism, carrying a total of 88 implants, were assigned either to an air abrasive with the glycine powder treatment group (AAD) or to a manual debridement and clorexidine administration treatment group (MDA). Clinical data were collected before treatment and at 3 and 6 months after the treatment. Plaque index (PI), bleeding index (BOP), probing depth (PD), clinical attachment level (CAL) and bleeding score (BS) were analysed. RESULTS: After 3 months, AAD treatment statistically significantly improved BS (P < 0.05); at 6 months, AAD treatment statistically significantly improved indexes PD, PI, BOP and BS (P < 0.05). In addition, the AAD treatment proved to be more effective than MDA in maintaining the peri-implant health of PD at three and 6 months, and of PI at 6 months (P < 0.05). There were no significant changes of CAL in both groups, and all the indexes remained within the physiological levels. CONCLUSIONS: Within the limits of the study, treatment with glycine seems appropriate in the maintenance of peri-implant health and more effective than the traditional treatment with plastic curette and chlorhexidine. PMID- 26842545 TI - Substantia nigra echogenicity correlated with clinical features of Parkinson's disease. AB - BACKGROUND: Transcranial sonography can display structural alterations in the substantia nigra (SN) of patients with Parkinson's disease (PD), and is considered to be a potential useful tool for the diagnosis of PD. The aim of this study was to assess the correlation between SN echogenicity and clinical features in Chinese patients with PD. METHODS: A total of 420 subjects including 290 patients with PD and 130 controls were recruited from the neurological clinic or the community. Transcranial sonographic evaluations of the SN were performed in all subjects, and motor and non-motor symptoms were thoroughly assessed by a series of rating scales in PD patients. RESULTS: Two hundred and one patients were successfully assessed by transcranial sonography. SN hyperechogenicity was found to be associated with male sex (p = 0.004), higher scores on the Unified Parkinson's Disease Rating Scale (UPDRS) part II (p = 0.001) and autonomic symptoms scores (p = 0.003). Moreover, regression analysis revealed that UPDRS part II scores (odds ratio = 1.141, p < 0.001) and gender (odds ratio = 2.409, p = 0.007) could be the independent predictors for SN hyperechogenicity; in addition, among all items of UPDRS part II, speech, dressing, hygiene, and turning in bed and adjusting bed clothes significantly correlated with SN hyperechogenicity. CONCLUSIONS: This is the first report suggesting the correlation between SN echogenicity and UPDRS part II, and we conclude that increased SN echogenicity might reflect more severe disease disability or poorer medical response. PMID- 26842544 TI - How a concerned family member, friend or member of the public can help someone with gambling problems: a Delphi consensus study. AB - BACKGROUND: Gambling is an enjoyable recreational pursuit for many people. However, for some it can lead to significant harms. The Delphi expert consensus method was used to develop guidelines for how a concerned family member, friend or member of the public can recognise the signs of gambling problems and support a person to change their gambling. METHODS: A systematic review of websites, books and journal articles was conducted to develop a questionnaire containing items about the knowledge, skills and actions needed for supporting a person with gambling problems. These items were rated over three rounds by two international expert panels comprising people with a lived experience of gambling problems and professionals who treat people with gambling problems or research gambling problems. RESULTS: A total of 66 experts (34 with lived experience and 32 professionals) rated 412 helping statements according to whether they thought the statements should be included in these guidelines. There were 234 helping statements that were endorsed by at least 80 % of members of both of the expert panels. These endorsed statements were used to develop the guidelines. CONCLUSION: Two groups of experts were able to reach substantial consensus on how someone can recognise the signs of gambling problems and support a person to change. PMID- 26842546 TI - First assessment of potential distribution and dispersal capacity of the emerging invasive mosquito Aedes koreicus in Northeast Italy. AB - BACKGROUND: Invasive alien species represent a growing threat for natural systems, economy and human health. Active surveillance and responses that readily suppress newly established colonies are effective actions to mitigate the noxious consequences of biological invasions. However, when an exotic species establishes a viable population in a new area, predicting its potential spread is the most effective way to implement adequate control actions. Emerging invasive species, despite monitoring efforts, are poorly known in terms of behaviour and capacity to adapt to the new invaded range. Therefore, tools that provide information on their spread by maximising the available data, are critical. METHODS: We apply three different approaches to model the potential distribution of an emerging invasive mosquito, Aedes koreicus, in Northeast Italy: 1) an automatic statistical approach based on information theory, 2) a statistical approach integrated with prior knowledge, and 3) a GIS physiology-based approach. Each approach possessed benefits and limitations, and the required ecological information increases on a scale from 1 to 3. We validated the model outputs using the only other known invaded area in Europe. Finally, we applied a road network analysis to the suitability surface with the highest prediction power to highlight those areas with the highest likelihood of invasion. RESULTS: The GIS physiological-based model had the highest prediction power. It showed that localities currently occupied by Aedes koreicus represent only a small fraction of the potentially suitable area. Furthermore, the modelled niche included areas as high as 1500 m a.s.l., only partially overlapping with Aedes albopictus distribution. CONCLUSIONS: The simulated spread indicated that all of the suitable portion of the study area is at risk of invasion in a relatively short period of time if no control policies are implemented. Stochastic events may further boost the invasion process, whereas competition with Aedes albopictus may limit it. According to our analysis, some of the major cities in the study area may have already been invaded. Further monitoring is needed to confirm this finding. The developed models and maps represent valuable tools to inform policies aimed at eradicating or mitigating Aedes koreicus invasion in Northeast Italy and Central Europe. PMID- 26842547 TI - Operationalizing Neuroimaging for Disorders of Consciousness: The Canadian Context. PMID- 26842548 TI - Exploring the impact of different multi-level measures of physician communities in patient-centric care networks on healthcare outcomes: A multi-level regression approach. AB - A patient-centric care network can be defined as a network among a group of healthcare professionals who provide treatments to common patients. Various multi level attributes of the members of this network have substantial influence to its perceived level of performance. In order to assess the impact different multi level attributes of patient-centric care networks on healthcare outcomes, this study first captured patient-centric care networks for 85 hospitals using health insurance claim dataset. From these networks, this study then constructed physician collaboration networks based on the concept of patient-sharing network among physicians. A multi-level regression model was then developed to explore the impact of different attributes that are organised at two levels on hospitalisation cost and hospital length of stay. For Level-1 model, the average visit per physician significantly predicted both hospitalisation cost and hospital length of stay. The number of different physicians significantly predicted only the hospitalisation cost, which has significantly been moderated by age, gender and Comorbidity score of patients. All Level-1 findings showed significance variance across physician collaboration networks having different community structure and density. These findings could be utilised as a reflective measure by healthcare decision makers. Moreover, healthcare managers could consider them in developing effective healthcare environments. PMID- 26842549 TI - [3D visualization and analysis of vocal fold dynamics]. AB - BACKGROUND: Visual investigation methods of the larynx mainly allow for the two dimensional presentation of the three-dimensional structures of the vocal fold dynamics. The vertical component of the vocal fold dynamics is often neglected, yielding a loss of information. The latest studies show that the vertical dynamic components are in the range of the medio-lateral dynamics and play a significant role within the phonation process. OBJECTIVES: This work presents a method for future 3D reconstruction and visualization of endoscopically recorded vocal fold dynamics. MATERIALS AND METHODS: The setup contains a high-speed camera (HSC) and a laser projection system (LPS). The LPS projects a regular grid on the vocal fold surfaces and in combination with the HSC allows a three-dimensional reconstruction of the vocal fold surface. Hence, quantitative information on displacements and velocities can be provided. The applicability of the method is presented for one ex-vivo human larynx, one ex-vivo porcine larynx and one synthetic silicone larynx. RESULTS: The setup introduced allows the reconstruction of the entire visible vocal fold surfaces for each oscillation status. This enables a detailed analysis of the three dimensional dynamics (i. e. displacements, velocities, accelerations) of the vocal folds. CONCLUSIONS: The next goal is the miniaturization of the LPS to allow clinical in-vivo analysis in humans. We anticipate new insight on dependencies between 3D dynamic behavior and the quality of the acoustic outcome for healthy and disordered phonation. PMID- 26842550 TI - Spectroscopy and Dynamics of Medium-Sized Molecules and Clusters: Theory, Experiment, and Applications. PMID- 26842552 TI - The effect of bladder contrast on dose calculation in volumetric modulated arc therapy planning in patients treated for postoperative prostate cancer. AB - PURPOSE: The aim of this study was to evaluate the effect of contrast agent on dose calculation in volumetric modulated arc therapy (VMAT) in the post prostatectomy setting. METHODS AND MATERIAL: Ten patients were studied. Each patient received planning computed tomography (CT) images with contrast agent. All of the plans were done on virtually simulated contrast-free CT scans. The plan approved by the radiation oncologist was replicated to the contrast CT series. In both of the plans the same monitor unit was used. The doses calculated from the two plans were compared in regard to target volumes and organs at risk. A paired sample t-test was used to evaluate the differences in cumulative dose volume histogram between the two plans. RESULTS: We showed that the use of contrast agent may cause significant differences in dose distribution. There was a significant decrease in doses received by planning target volume (PTV70), rectum V65 Gy, rectum V40 Gy, bladder V65 Gy, penile bulb V40 Gy in plans with contrast-enhanced CT sets. The decrease in mean, maximum and minimum doses received by PTV70 also contributed to the significant decrease in conformity index. CONCLUSIONS: Using a contrast agent at the time of CT simulation may cause significant differences in dose distribution. For this reason, the plan should always be carried out on non-contrast CT data sets to avoid additional errors in the treatment planning process. PMID- 26842553 TI - Parallel Microcracks-based Ultrasensitive and Highly Stretchable Strain Sensors. AB - There is an increasing demand for flexible, skin-attachable, and wearable strain sensors due to their various potential applications. However, achieving strain sensors with both high sensitivity and high stretchability is still a grand challenge. Here, we propose highly sensitive and stretchable strain sensors based on the reversible microcrack formation in composite thin films. Controllable parallel microcracks are generated in graphite thin films coated on elastomer films. Sensors made of graphite thin films with short microcracks possess high gauge factors (maximum value of 522.6) and stretchability (epsilon >= 50%), whereas sensors with long microcracks show ultrahigh sensitivity (maximum value of 11,344) with limited stretchability (epsilon <= 50%). We demonstrate the high performance strain sensing of our sensors in both small and large strain sensing applications such as human physiological activity recognition, human body large motion capturing, vibration detection, pressure sensing, and soft robotics. PMID- 26842554 TI - Cross-cultural challenges in assessing medical professionalism among emergency physicians in a Middle Eastern Country (Bahrain): feasibility and psychometric properties of multisource feedback. AB - BACKGROUND: Multisource feedback (MSF) is an evaluation tool whereby surveys assessing physicians are administered among medical peers and colleagues. Such evaluations provide physicians with non-biased valuations of both their strengths and their weaknesses, offering an opportunity for improvement in their work. Studies have shown that MSF is particularly effective for emergency care physicians. METHODS: The study was undertaken in a military teaching hospital in Bahrain. A total of 30 emergency physicians (the total number of emergency physicians in our hospital), 16 males and 14 females, were evaluated using multisource feedback. Each emergency physician was assessed by three groups of raters, including 4 emergency physicians, 4 referral physicians from other departments, and 4 coworkers from within the emergency department. Feasibility of the questionnaire was analyzed via response rates, average time required to complete it, and the number of raters required to produce reliable results. We used exploratory factor analysis to examine for the construct validity. Cronbach's coefficient was calculated to measure the internal consistency reliability of the instrument. RESULTS: The total mean response rate was 74.2 %, and the self-reported average time needed to fill out each survey was 4.3 min, indicating a good feasibility of the questionnaire. Reliability analysis indicated that the full-scale instrument had high internal consistency (Cronbach's alpha 0.98). Factor analysis showed that the data on the questionnaire decomposed into three factors, which accounted for 72.6 % of the total variance: professionalism, collaboration, and communication. The generalizability coefficients (Ep(2)) were 0.76 for the surveys. Out of the 30 candidates, 26 participated in the knowledge test. The total mean score of the knowledge exam was 34.52, with scores ranging from 17 to 54. CONCLUSIONS: Based on this study's results, we conclude that the instruments and procedures used have high reliability, validity, and feasibility in assessing the emergency physician in the emergency department in our clinical setting in the Middle East. The item analyses, reliability, and factor analyses all indicate that these instruments are effective in assessing emergency physicians. PMID- 26842555 TI - Effects of Public Hospital Reform on Inpatient Expenditures in Rural China. AB - Public hospital reform is one priority area in the healthcare system reform that China launched in 2009. The Chinese government invested over $10bn for pilot projects in public hospital reform in rural China. However, little evidence exists on their effects. Using a quasi-natural experiment design, we evaluated the effects of a public hospital pilot project in Hubei province on inpatient spending. We obtained inpatient claims data from 1/1/2011 through 6/30/2013 for enrollees in the New Cooperative Medical Scheme in two counties: Danjiangkou, one of the pilot counties selected for reform in September 2012, and Laohekou, a similar, adjacent county serving as the control group. Using a difference-in differences approach with propensity score weighting, we found that total inpatient spending increased Y1160 (95% CI 1155-1166), out-of-pocket spending increased Y385 (95% CI 382-389), length of stay increased 0.51 days (95% CI 0.50 0.52), but inpatient medication spending decreased Y147 (95% CI 145-150), post policy in Danjiangkou, relative to the control group. The overall reimbursement rate increased by 5.7 percentage points. One of the goals of the recent public hospital reform is to make inpatient services affordable to patients. We found that although patients spent less on inpatient medications, total out-of-pocket spending increased considerably after reform. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26842556 TI - Induction and differentiation of adipose-derived stem cells from human buccal fat pads into salivary gland cells. AB - Atrophy or hypofunction of the salivary gland because of aging or disease leads to hyposalivation that affects patient quality of life by causing dry mouth, deterioration of mastication/deglutition, and poor oral hygiene status. Current therapy for atrophy or hypofunction of the salivary gland in clinical practice focuses on symptom relief using drugs and artificial saliva; therefore, there is still a need to develop new therapies. To investigate potential novel therapeutic targets, we induced the differentiation of salivary gland cells by co-culturing human adipose-derived stem cells isolated from buccal fat pads (hBFP-ASCs) with human salivary-gland-derived fibroblasts (hSG-fibros). We examined their potential for transplantation and tissue neogenesis. Following the culture of hBFP-ASCs and hSG-fibros, differentiated cells were transplanted into the submandibular glands of SCID mice, and their degree of differentiation in tissues was determined. We also examined their potential for functional tissue reconstitution using a three-dimensional (3D) culture system. Co-cultured cells expressed salivary-glandrelated markers and generated new tissues following transplantation in vivo. Moreover, cell reconstituted glandular structures in the 3D culture system. In conclusion, coculture of hSG-fibros with hBFP-ASCs led to successful differentiation into salivary gland cells that could be transplanted to generate new tissues. PMID- 26842557 TI - ALDH2 polymorphism for the risk of cervical carcinogenesis. AB - To investigate the clinical significance of ALDH2 genetic polymorphisms in cervical carcinogenesis. ALDH2 polymorphisms together with human papillomavirus (HPV) types were examined in a total of 195 cervical smear in exfoliated cervical cell samples using Real-Time polymerase chain reaction (PCR) System. The frequency for the AG+AA genotype was seven in the normal group (70.0 %), 16 in the LSIL group (57.1 %), and 27 in the HSIL group (90.0 %). A significant difference was found between the LSIL and HSIL groups (P = 0.0064). Patients with HSIL lesions frequently had high-risk HPV infections and concurrently belonged to the AG+AA group. ALDH2 genotype in cervical cell samples may be associated with more severe precancerous lesions of the cervix in a Japanese population. PMID- 26842558 TI - Imaging hamster model of bile duct cancer in vivo using fluorescent L-glucose derivatives. AB - Extrahepatic bile duct cancer (cholangiocarcinoma) has a poor prognosis. Since surgical resection is the only way to prolong the patient's life, it is of critical importance to correctly determine the extent of lesions. However, conventional pre-operative assessments have insufficient spatial resolution for determining the surgical margin. A fluorescent contrast agent might provide a more precise measure to identify anomalies in biliary surface, when combined with probe-based confocal laser endomicroscopy (pCLE). We have previously shown that 2 [N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-L-glucose (2-NBDLG), a fluorescent derivative of L-glucose (fLG), is specifically taken up into spheroids consisting of cells showing heterogeneous nuclear-cytoplasm ratio, a feature of malignant cells in clinical settings. In addition, a combined use of 2 TRLG, a membrane-impermeable fLG, with 2-NBDLG visualized membrane integrity as well. We therefore explored in the present study the availability of the fLGs in vivo as a contrast agent for pCLE by using a hamster model of cholangiocarcinoma. Extrahepatic cholangiocarcinoma developed in mid common duct in ~20 % of the animals subjected to cholecystoduodenostomy with the ligation at the distal end of the common duct followed by injection of a carcinogen N-nitrosobis(2 oxopropyl)amine. After infusing bile duct with a solution containing 2-NBDLG and 2-TRLG, the lumen was surgically exposed and examined by pCLE. Fluorescence pattern characterized by bright spots and dark clumps was detected in the areas diagnosed with cholangiocarcinoma in later histopathology, whereas no such pattern was detected in control animals. These findings may form a basis for elucidating a potential availability of fLGs in imaging cholangiocarcinoma by pCLE. PMID- 26842560 TI - Transcranial direct current stimulation improves seizure control in patients with Rasmussen encephalitis. AB - Rasmussen encephalitis is associated with severe seizures that are unresponsive to antiepileptic drugs, as well as immunosuppressants. Transcranial direct current stimulation (t-DCS) is a non-invasive and safe method tried mostly for focal epilepsies with different aetiologies. To date, there is only one published study with two case reports describing the effect of t-DCS in Rasmussen encephalitis. Our aim was to investigate the effect of t-DCS on seizures in Rasmussen encephalitis and to clarify its safety. Five patients (mean age: 19; three females), diagnosed with Rasmussen encephalitis were included in this study. Patients received first cathodal, then anodal (2 mA for 30 minutes on three consecutive days for non-sham stimulations), and finally sham stimulation with two-month intervals, respectively. Three patients received classic (DC) cathodal t-DCS whereas two patients received cathodal stimulation with amplitude modulation at 12 Hz. Afterwards, all patients received anodal stimulation with amplitude modulation at 12 Hz. In the last part of the trial, sham stimulation (a 60-second stimulation with gradually decreasing amplitude to zero in the last 15 seconds) was applied to three patients. Maximum current density was 571 mA/m2 using 70 mm x 50 mm wet sponge electrodes with 2-mA maximum, current controlled stimulator, and maximum charge density was 1028 C/m2 for a 30-minute stimulation period. After cathodal stimulation, all but one patient had a greater than 50% decrease in seizure frequency. Two patients who received modulated cathodal t-DCS had better results. The longest positive effect lasted for one month. A second trial with modulated anodal stimulation and a third with sham stimulation were not effective. No adverse effect was reported with all types of stimulations. Both classic and modulated cathodal t-DCS may be suitable alternative methods for improving seizure outcome in Rasmussen encephalitis patients. PMID- 26842559 TI - Endothelial progenitor cells and neural progenitor cells synergistically protect cerebral endothelial cells from Hypoxia/reoxygenation-induced injury via activating the PI3K/Akt pathway. AB - BACKGROUND: Protection of cerebral endothelial cells (ECs) from hypoxia/reoxygenation (H/R)-induced injury is an important strategy for treating ischemic stroke. In this study, we investigated whether co-culture with endothelial progenitor cells (EPCs) and neural progenitor cells (NPCs) synergistically protects cerebral ECs against H/R injury and the underlying mechanism. RESULTS: EPCs and NPCs were respectively generated from inducible pluripotent stem cells. Human brain ECs were used to produce an in vitro H/R injury model. Data showed: 1) Co-culture with EPCs and NPCs synergistically inhibited H/R-induced reactive oxygen species (ROS) over-production, apoptosis, and improved the angiogenic and barrier functions (tube formation and permeability) in H/R-injured ECs. 2) Co-culture with NPCs up-regulated the expression of vascular endothelial growth factor receptor 2 (VEGFR2). 3) Co culture with EPCs and NPCs complementarily increased vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) levels in conditioned medium, and synergistically up-regulated the expression of p-Akt/Akt and p Flk1/VEGFR2 in H/R-injured ECs. 4) Those effects could be decreased or abolished by inhibition of both VEGFR2 and tyrosine kinase B (TrkB) or phosphatidylinositol 3-kinase (PI3K). CONCLUSIONS: Our data demonstrate that EPCs and NPCs synergistically protect cerebral ECs from H/R-injury, via activating the PI3K/Akt pathway which mainly depends on VEGF and BDNF paracrine. PMID- 26842562 TI - Spanish Consensus Guidelines on prophylaxis with bypassing agents in patients with haemophilia and inhibitors. AB - Prophylaxis with the blood clotting factor, factor VIII (FVIII) is ineffective for individuals with haemophilia A and high-titre inhibitors to FVIII. Prophylaxis with the FVIII bypassing agents activated prothrombin complex concentrates (aPCC; FEIBA(r) Baxalta) or recombinant activated factor VII (rFVIIa; Novo-Seven(r), Novo Nordisk) may be an effective alternative. It was our aim to develop evidence -and expert opinion- based guidelines for prophylactic therapy for patients with high-titre inhibitors to FVIII. A panel of nine Spanish haematologists undertook a systematic review of the literature to develop consensus-based guidance. Particular consideration was given to prophylaxis in patients prior to undergoing immune tolerance induction (ITI) (a process of continued exposure to FVIII that can restore sensitivity for some patients), during the ITI period and for those not undergoing ITI or for whom ITI had failed. These guidelines offer guidance for clinicians in deciding which patients might benefit from prophylaxis with FVIII bypassing agents, the most appropriate agents in various clinical settings related to ITI, doses and dosing regimens and how best to monitor the efficacy of prophylaxis. The paper includes recommendations on when to interrupt or stop prophylaxis and special safety concerns during prophylaxis. These consensus guidelines offer the most comprehensive evaluation of the clinical evidence base to date and should be of considerable benefit to clinicians facing the challenge of managing patients with severe haemophilia A with high-titre FVIII inhibitors. PMID- 26842561 TI - Evaluation of a Heparin-Calibrated Antifactor Xa Assay for Measuring the Anticoagulant Effect of Oral Direct Xa Inhibitors. AB - The introduction of oral direct anti-Xa anticoagulants apixaban and rivaroxaban has significantly impacted the treatment and prevention of thromboembolic disease. Clinical scenarios exist in which a quantitative assessment for degree of anticoagulation due to these agents would aid management. The purpose of this work was to evaluate the chromogenic antifactor Xa assay calibrated with heparin standards at our institution for assessment of intensity of anticoagulation with rivaroxaban or apixaban in addition to its current use for unfractionated heparin or low-molecular-weight heparin. We also aimed to propose expected steady state peak and trough antifactor Xa activities for these agents based upon dosing regimens approved for nonvalvular atrial fibrillation. Antifactor Xa activity correlated very strongly with apixaban and rivaroxaban concentration in both spiked samples and treated patient plasma samples (r (2) = .99, P < .001). This correlation was observed over a broad range (20-500 ng/mL) of drug concentrations, as sample dilution with pooled normal plasma significantly extended the range of quantitative assessment. Based on drug concentrations previously published in pharmacokinetic studies, the expected steady state peak and trough antifactor Xa activity ranges for apixaban are 1.80 to 2.20 IU/mL and 0.70 to 1.10 IU/mL, respectively. For rivaroxaban, these ranges are 3.80 to 6.20 IU/mL and 0.60 to 1.00 IU/mL, respectively. In conclusion, our findings demonstrate that heparin-calibrated antifactor Xa activity correlates strongly with apixaban and rivaroxaban concentration. The dilution of samples allowed for this correlation to be extended over the majority of on-therapy drug concentrations. PMID- 26842563 TI - CrossTalk opposing view: Interstitial cells are not involved and physiologically important in neuromuscular transmission in the gut. PMID- 26842565 TI - Current approaches neglect possible agricultural cutback under large-scale organic farming. A comment to Ponisio et al. PMID- 26842566 TI - Predators inhibit brain cell proliferation in natural populations of electric fish, Brachyhypopomus occidentalis. AB - Compared with laboratory environments, complex natural environments promote brain cell proliferation and neurogenesis. Predators are one important feature of many natural environments, but, in the laboratory, predatory stimuli tend to inhibit brain cell proliferation. Often, laboratory predatory stimuli also elevate plasma glucocorticoids, which can then reduce brain cell proliferation. However, it is unknown how natural predators affect cell proliferation or whether glucocorticoids mediate the neurogenic response to natural predators. We examined brain cell proliferation in six populations of the electric fish, Brachyhypopomus occidentalis, exposed to three forms of predator stimuli: (i) natural variation in the density of predatory catfish; (ii) tail injury, presumably from predation attempts; and (iii) the acute stress of capture. Populations with higher predation pressure had lower density of proliferating (PCNA+) cells, and fish with injured tails had lower proliferating cell density than those with intact tails. However, plasma cortisol did not vary at the population level according to predation pressure or at the individual level according to tail injury. Capture stress significantly increased cortisol, but only marginally decreased cell proliferation. Thus, it appears that the presence of natural predators inhibits brain cell proliferation, but not via mechanisms that depend on changes in basal cortisol levels. This study is the first demonstration of predator-induced alteration of brain cell proliferation in a free-living vertebrate. PMID- 26842564 TI - Chromatin-associated degradation is defined by UBXN-3/FAF1 to safeguard DNA replication fork progression. AB - The coordinated activity of DNA replication factors is a highly dynamic process that involves ubiquitin-dependent regulation. In this context, the ubiquitin directed ATPase CDC-48/p97 recently emerged as a key regulator of chromatin associated degradation in several of the DNA metabolic pathways that assure genome integrity. However, the spatiotemporal control of distinct CDC-48/p97 substrates in the chromatin environment remained unclear. Here, we report that progression of the DNA replication fork is coordinated by UBXN-3/FAF1. UBXN 3/FAF1 binds to the licensing factor CDT-1 and additional ubiquitylated proteins, thus promoting CDC-48/p97-dependent turnover and disassembly of DNA replication factor complexes. Consequently, inactivation of UBXN-3/FAF1 stabilizes CDT-1 and CDC-45/GINS on chromatin, causing severe defects in replication fork dynamics accompanied by pronounced replication stress and eventually resulting in genome instability. Our work identifies a critical substrate selection module of CDC 48/p97 required for chromatin-associated protein degradation in both Caenorhabditis elegans and humans, which is relevant to oncogenesis and aging. PMID- 26842567 TI - Ancient origin of high taxonomic richness among insects. AB - Insects are a hyper-diverse group, comprising nearly three-quarters of all named animal species on the Earth, but the environmental drivers of their richness and the roles of ecological interactions and evolutionary innovations remain unclear. Previous studies have argued that family-level insect richness increased continuously over the evolutionary history of the group, but inclusion of extant family records artificially inflated the relative richness of younger time intervals. Here we apply sampling-standardization methods to a species-level database of fossil insect occurrences, removing biases present in previous richness curves. We show that insect family-richness peaked 125 Ma and that Recent values are only 1.5-3 times as high as the Late Palaeozoic. Rarefied species-richness data also tentatively suggest little or no net increase in richness over the past 125 Myr. The Cretaceous peak in family richness was coincident with major radiations within extant groups but occurred prior to extinctions within more basal groups. Those extinctions may in part be linked to mid-Cretaceous floral turnover following the evolution of flowering plants. Negligible net richness change over the past 125 Myr implies that major radiations within extant groups were offset by reduced richness within groups that are now relict or extinct. PMID- 26842568 TI - Matching-centrality decomposition and the forecasting of new links in networks. AB - Networks play a prominent role in the study of complex systems of interacting entities in biology, sociology, and economics. Despite this diversity, we demonstrate here that a statistical model decomposing networks into matching and centrality components provides a comprehensive and unifying quantification of their architecture. The matching term quantifies the assortative structure in which node makes links with which other node, whereas the centrality term quantifies the number of links that nodes make. We show, for a diverse set of networks, that this decomposition can provide a tight fit to observed networks. Then we provide three applications. First, we show that the model allows very accurate prediction of missing links in partially known networks. Second, when node characteristics are known, we show how the matching-centrality decomposition can be related to this external information. Consequently, it offers us a simple and versatile tool to explore how node characteristics explain network architecture. Finally, we demonstrate the efficiency and flexibility of the model to forecast the links that a novel node would create if it were to join an existing network. PMID- 26842569 TI - Regulatory links between imprinted genes: evolutionary predictions and consequences. AB - Genomic imprinting is essential for development and growth and plays diverse roles in physiology and behaviour. Imprinted genes have traditionally been studied in isolation or in clusters with respect to cis-acting modes of gene regulation, both from a mechanistic and evolutionary point of view. Recent studies in mammals, however, reveal that imprinted genes are often co-regulated and are part of a gene network involved in the control of cellular proliferation and differentiation. Moreover, a subset of imprinted genes acts in trans on the expression of other imprinted genes. Numerous studies have modulated levels of imprinted gene expression to explore phenotypic and gene regulatory consequences. Increasingly, the applied genome-wide approaches highlight how perturbation of one imprinted gene may affect other maternally or paternally expressed genes. Here, we discuss these novel findings and consider evolutionary theories that offer a rationale for such intricate interactions among imprinted genes. An evolutionary view of these trans-regulatory effects provides a novel interpretation of the logic of gene networks within species and has implications for the origin of reproductive isolation between species. PMID- 26842570 TI - The evolutionary convergence of mid-Mesozoic lacewings and Cenozoic butterflies. AB - Mid-Mesozoic kalligrammatid lacewings (Neuroptera) entered the fossil record 165 million years ago (Ma) and disappeared 45 Ma later. Extant papilionoid butterflies (Lepidoptera) probably originated 80-70 Ma, long after kalligrammatids became extinct. Although poor preservation of kalligrammatid fossils previously prevented their detailed morphological and ecological characterization, we examine new, well-preserved, kalligrammatid fossils from Middle Jurassic and Early Cretaceous sites in northeastern China to unravel a surprising array of similar morphological and ecological features in these two, unrelated clades. We used polarized light and epifluorescence photography, SEM imaging, energy dispersive spectrometry and time-of-flight secondary ion mass spectrometry to examine kalligrammatid fossils and their environment. We mapped the evolution of specific traits onto a kalligrammatid phylogeny and discovered that these extinct lacewings convergently evolved wing eyespots that possibly contained melanin, and wing scales, elongate tubular proboscides, similar feeding styles, and seed-plant associations, similar to butterflies. Long-proboscid kalligrammatid lacewings lived in ecosystems with gymnosperm-insect relationships and likely accessed bennettitalean pollination drops and pollen. This system later was replaced by mid-Cretaceous angiosperms and their insect pollinators. PMID- 26842571 TI - System-level approach needed to evaluate the transition to more sustainable agriculture. PMID- 26842572 TI - What can be learnt from wheel-running by wild mice, and how can we identify when wheel-running is pathological? PMID- 26842574 TI - Inter- and intraspecific conflicts between parasites over host manipulation. AB - Host manipulation is a common strategy by which parasites alter the behaviour of their host to enhance their own fitness. In nature, hosts are usually infected by multiple parasites. This can result in a conflict over host manipulation. Studies of such a conflict in experimentally infected hosts are rare. The cestode Schistocephalus solidus (S) and the nematode Camallanus lacustris (C) use copepods as their first intermediate host. They need to grow for some time inside this host before they are infective and ready to be trophically transmitted to their subsequent fish host. Accordingly, not yet infective parasites manipulate to suppress predation. Infective ones manipulate to enhance predation. We experimentally infected laboratory-bred copepods in a manner that resulted in copepods harbouring (i) an infective C plus a not yet infective C or S, or (ii) an infective S plus a not yet infective C. An infective C completely sabotaged host manipulation by any not yet infective parasite. An infective S partially reduced host manipulation by a not yet infective C. We hence show experimentally that a parasite can reduce or even sabotage host manipulation exerted by a parasite from a different species. PMID- 26842573 TI - High proportion of smaller ranged hummingbird species coincides with ecological specialization across the Americas. AB - Ecological communities that experience stable climate conditions have been speculated to preserve more specialized interspecific associations and have higher proportions of smaller ranged species (SRS). Thus, areas with disproportionally large numbers of SRS are expected to coincide geographically with a high degree of community-level ecological specialization, but this suggestion remains poorly supported with empirical evidence. Here, we analysed data for hummingbird resource specialization, range size, contemporary climate, and Late Quaternary climate stability for 46 hummingbird-plant mutualistic networks distributed across the Americas, representing 130 hummingbird species (ca 40% of all hummingbird species). We demonstrate a positive relationship between the proportion of SRS of hummingbirds and community-level specialization, i.e. the division of the floral niche among coexisting hummingbird species. This relationship remained strong even when accounting for climate, furthermore, the effect of SRS on specialization was far stronger than the effect of specialization on SRS, suggesting that climate largely influences specialization through species' range-size dynamics. Irrespective of the exact mechanism involved, our results indicate that communities consisting of higher proportions of SRS may be vulnerable to disturbance not only because of their small geographical ranges, but also because of their high degree of specialization. PMID- 26842575 TI - Invader or resident? Ancient-DNA reveals rapid species turnover in New Zealand little penguins. AB - The expansion of humans into previously unoccupied parts of the globe is thought to have driven the decline and extinction of numerous vertebrate species. In New Zealand, human settlement in the late thirteenth century AD led to the rapid demise of a distinctive vertebrate fauna, and also a number of 'turnover' events where extinct lineages were subsequently replaced by closely related taxa. The recent genetic detection of an Australian little penguin (Eudyptula novaehollandiae) in southeastern New Zealand may potentially represent an additional 'cryptic' invasion. Here we use ancient-DNA (aDNA) analysis and radiocarbon dating of pre-human, archaeological and historical Eudyptula remains to reveal that the arrival of E. novaehollandiae in New Zealand probably occurred between AD 1500 and 1900, following the anthropogenic decline of its sister taxon, the endemic Eudyptula minor. This rapid turnover event, revealed by aDNA, suggests that native species decline can be masked by invasive taxa, and highlights the potential for human-mediated biodiversity shifts. PMID- 26842576 TI - Phylogeny and adaptation shape the teeth of insular mice. AB - By accompanying human travels since prehistorical times, the house mouse dispersed widely throughout the world, and colonized many islands. The origin of the travellers determined the phylogenetic source of the insular mice, which encountered diverse ecological and environmental conditions on the various islands. Insular mice are thus an exceptional model to disentangle the relative role of phylogeny, ecology and climate in evolution. Molar shape is known to vary according to phylogeny and to respond to adaptation. Using for the first time a three-dimensional geometric morphometric approach, compared with a classical two dimensional quantification, the relative effects of size variation, phylogeny, climate and ecology were investigated on molar shape diversity across a variety of islands. Phylogeny emerged as the factor of prime importance in shaping the molar. Changes in competition level, mostly driven by the presence or absence of the wood mouse on the different islands, appeared as the second most important effect. Climate and size differences accounted for slight shape variation. This evidences a balanced role of random differentiation related to history of colonization, and of adaptation possibly related to resource exploitation. PMID- 26842577 TI - Low doses of a neonicotinoid insecticide modify pheromone response thresholds of central but not peripheral olfactory neurons in a pest insect. AB - Insect pest management relies mainly on neurotoxic insecticides, including neonicotinoids, leaving residues in the environment. There is now evidence that low doses of insecticides can have positive effects on pest insects by enhancing various life traits. Because pest insects often rely on sex pheromones for reproduction, and olfactory synaptic transmission is cholinergic, neonicotinoid residues could modify chemical communication. We recently showed that treatments with different sublethal doses of clothianidin could either enhance or decrease behavioural sex pheromone responses in the male moth, Agrotis ipsilon. We investigated now effects of the behaviourally active clothianidin doses on the sensitivity of the peripheral and central olfactory system. We show with extracellular recordings that both tested clothianidin doses do not influence pheromone responses in olfactory receptor neurons. Similarly, in vivo optical imaging does not reveal any changes in glomerular response intensities to the sex pheromone after clothianidin treatments. The sensitivity of intracellularly recorded antennal lobe output neurons, however, is upregulated by a lethal dose 20 times and downregulated by a dose 10 times lower than the lethal dose 0. This correlates with the changes of behavioural responses after clothianidin treatment and suggests the antennal lobe as neural substrate involved in clothianidin induced behavioural changes. PMID- 26842579 TI - Analysis and fragmentation mechanisms of hirsutinolide-type sesquiterpene lactones by ultra-high-performance liquid chromatography/electrospray ionization linear ion trap Orbitrap mass spectrometry. AB - RATIONALE: Hirsutinolide-type sesquiterpene lactones (SLs) are natural biologically active compounds mainly found in the genus Vernonia. Very few studies have been published about the fragmentation mechanisms of SLs generally and none about hirsutinolides, although they have drawn attention through their biological and taxonomical interest. This work aims to propose a mass spectrometry fragmentation pattern for hirsutinolides in order to detect and to identify them in a botanical extract. METHODS: The fragmentation pathways of six pure hirsutinolides isolated from Pseudelephantopus spiralis were established by positive ion electrospray high-resolution linear ion trap Orbitrap tandem mass spectrometry (ESI(+)-HRMS(n) ). A resolutive, hyphenated ultra-high-performance liquid chromatography (UHPLC) coupled to diode array detection (DAD) and ESI(+) HRMS(n) method was then implemented to separate and analyze them. The ionization behaviour and diagnostic product ions were investigated by both methods. The UHPLC/DAD-ESI-HRMS(n) method was applied for the dereplication of a plant extract. RESULTS: For the six standard compounds, the main fragmentation pattern consists first in the loss of the side chain in the C-8 position followed by the loss of the substituent in the C-13 position. UHPLC/HRMS analyses of hirsutinolides mainly produced sodiated molecules or [M+H-H2 O](+) ions. The high abundance product ions at m/z 299 and 259 were established to be the characteristic diagnostic ions of the hirsutinolide core. The analysis of a P. spiralis extract further led to the identification of two putative hirsutinolides. CONCLUSIONS: The UHPLC/DAD-HRMS(n) method combining characteristic fragmentation patterns and the profiles of the product ions generated in the MS and MS/MS spectra is an effective technique for characterizing hirsutinolide-type SLs. PMID- 26842578 TI - Targeted absolute quantitative proteomics with SILAC internal standards and unlabeled full-length protein calibrators (TAQSI). AB - RATIONALE: Liquid Chromatography/Mass Spectrometry (LC/MS)-based proteomics for absolute protein quantification has been increasingly utilized in both basic and clinical research. There is a great need to overcome some major hurdles of current absolute protein quantification methods, such as significant inter-assay variability and the high cost associated with the preparation of purified stable isotope-labeled peptide/protein standards. METHODS: We developed a novel targeted absolute protein quantification method, named TAQSI, utilizing full-length isotope-labeled protein internal standards generated from SILAC (stable isotope labeling by amino acid in cell culture) and unlabeled full-length protein calibrators. This approach was applied to absolute quantification of carboxylesterase 1 (CES1), the primary human hepatic hydrolase, in a large set of human liver samples. Absolute CES1 quantities were derived from the standard calibration curves established from unlabeled CES1 protein calibrators and the isotope-labeled CES1 internal standards obtained from SILAC HepG2 cells. RESULTS: The TAQSI assay was found to be accurate, precise, reproducible, and cost effective. Importantly, protein quantification was not affected by various protein extraction and digestion protocols, and measurement errors associated with nonsynonymous variants can be readily identified and avoided. Furthermore, the TAQSI approach significantly simplifies the procedure of identifying the best performance surrogate peptides. CONCLUSIONS: The TAQSI assay can be widely used for targeted absolute protein quantification in various biomedical research and clinical practice settings. PMID- 26842581 TI - Structural elucidation of AgAsS2 glass by the analysis of clusters formed during laser desorption ionisation applying quadrupole ion trap time-of-flight mass spectrometry. AB - RATIONALE: The structure of AgA(s)S2 glass, which has a broad range of applications, is still not well understood and a systematic mass spectrometric analysis of AgA(s)S2 glass is currently not available. Elucidation of the structure should help in the development of this material. METHODS: The AgA(s)S2 glass was prepared by the melt-quenched technique. Laser desorption ionisation (LDI) using quadrupole ion trap time-of-flight mass spectrometry (QIT-TOFMS) was used to follow the generation of Ag(m)As(n)S(x) clusters. The stoichiometry of the clusters generated was determined via collision-induced dissociation (CID) and modelling of isotopic patterns. The AgA(s)S2 glass was characterised by transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) spectroscopy. RESULTS: The LDI of AgA(s)S2 glass leads to the formation of unary (Ag+/- and As(3+)) species, 38 binary (As(n)S(x), Ag(m)S(x)), and 98 ternary (Ag(m)As(n)S(x)) singly charged clusters. The formation of silver-rich nano-grains during AgA(s)S2 glass synthesis has been identified using TEM analysis and also verified by QIT-TOFMS. CONCLUSIONS: TOFMS was shown to be a useful technique to study the generation of Ag(m)As(n)S(x )clusters. SEM, TEM and EDX analysis proved that the structure of AgA(s)S2 glass is 'grain-like' where grains are either: (1) Silver-rich 'islands' (Ag(m,) m up to 39) connected by arsenic and/or sulfur or arsenic sulfide chains or (2) silver sulfide (Ag2S)m (m = 9-20) clusters also similarly inter-connected. This obtained structural information may be useful for the development of ultra-high-density phase-change storage and memory devices using this kind of glass as a base. PMID- 26842580 TI - Analysis of human plasma metabolites across different liquid chromatography/mass spectrometry platforms: Cross-platform transferable chemical signatures. AB - RATIONALE: The metabolite profiling of a NIST plasma Standard Reference Material (SRM 1950) on different liquid chromatography/mass spectrometry (LC/MS) platforms showed significant differences. Although these findings suggest caution when interpreting metabolomics results, the degree of overlap of both profiles allowed us to use tandem mass spectral libraries of recurrent spectra to evaluate to what extent these results are transferable across platforms and to develop cross platform chemical signatures. METHODS: Non-targeted global metabolite profiles of SRM 1950 were obtained on different LC/MS platforms using reversed-phase chromatography and different chromatographic scales (conventional HPLC, UHPLC and nanoLC). The data processing and the metabolite differential analysis were carried out using publically available (XCMS), proprietary (Mass Profiler Professional) and in-house software (NIST pipeline). RESULTS: Repeatability and intermediate precision showed that the non-targeted SRM 1950 profiling was highly reproducible when working on the same platform (relative standard deviation (RSD) <2%); however, substantial differences were found in the LC/MS patterns originating on different platforms or even using different chromatographic scales (conventional HPLC, UHPLC and nanoLC) on the same platform. A substantial degree of overlap (common molecular features) was also found. A procedure to generate consistent chemical signatures using tandem mass spectral libraries of recurrent spectra is proposed. CONLUSIONS: Different platforms rendered significantly different metabolite profiles, but the results were highly reproducible when working within one platform. Tandem mass spectral libraries of recurrent spectra are proposed to evaluate the degree of transferability of chemical signatures generated on different platforms. Chemical signatures based on our procedure are most likely cross-platform transferable. PMID- 26842582 TI - Laser dissection sampling modes for direct mass spectral analysis. AB - RATIONALE: Laser microdissection coupled directly with mass spectrometry provides the capability of on-line analysis of substrates with high spatial resolution, high collection efficiency, and freedom on shape and size of the sampling area. Establishing the merits and capabilities of the different sampling modes that the system provides is necessary in order to select the best sampling mode for characterizing analytically challenging samples. METHODS: The capabilities of laser ablation spot sampling, laser ablation raster sampling, and laser 'cut and drop' sampling modes of a hybrid optical microscopy/laser ablation liquid vortex capture electrospray ionization mass spectrometry system were compared for the analysis of single cells and tissue. RESULTS: Single Chlamydomonas reinhardtii cells were monitored for their monogalactosyldiacylglycerol (MGDG) and diacylglyceryltrimethylhomo-Ser (DGTS) lipid content using the laser spot sampling mode, which was capable of ablating individual cells (~4-15 MUm) even when agglomerated together. Turbid Allium Cepa cells (~150 MUm) having unique shapes difficult to precisely measure using the other sampling modes could be ablated in their entirety using laser raster sampling. Intact microdissections of specific regions of a cocaine-dosed mouse brain tissue were compared using laser 'cut and drop' sampling. Since in laser 'cut and drop' sampling whole and otherwise unmodified sections are captured into the probe, 100% collection efficiencies were achieved. Laser ablation spot sampling has the highest spatial resolution of any sampling mode, while laser ablation raster sampling has the highest sampling area adaptability of the sampling modes. CONCLUSIONS: Laser ablation spot sampling has the highest spatial resolution of any sampling mode, useful in this case for the analysis of single cells. Laser ablation raster sampling was best for sampling regions with unique shapes that are difficult to measure using other sampling modes. Laser 'cut and drop' sampling can be used for cases where the highest sensitivity is needed, for example, monitoring drugs present in trace amounts in tissue. PMID- 26842583 TI - N2O source partitioning in soils using (15)N site preference values corrected for the N2O reduction effect. AB - RATIONALE: The aim of this study was to determine the impact of isotope fractionation associated with N2O reduction during soil denitrification on N2O site preference (SP) values and hence quantify the potential bias on SP-based N2O source partitioning. METHODS: The N2O SP values (n = 431) were derived from six soil incubation studies in N2-free atmosphere, and determined by isotope ratio mass spectrometry (IRMS). The N2 and N2O concentrations were measured directly by gas chromatography. Net isotope effects (NIE) during N2O reduction to N2 were compensated for using three different approaches: a closed-system model, an open system model and a dynamic apparent NIE function. The resulting SP values were used for N2O source partitioning based on a two end-member isotopic mass balance. RESULTS: The average SP0 value, i.e. the average SP values of N2O prior to N2O reduction, was recalculated with the closed-system model, resulting in -2.6 0/00 (+/-9.5), while the open-system model and the dynamic apparent NIE model gave average SP0 values of 2.9 0/00 (+/-6.3) and 1.7 0/00 (+/-6.3), respectively. The average source contribution of N2O from nitrification/fungal denitrification was 18.7% (+/-21.0) according to the closed-system model, while the open-system model and the dynamic apparent NIE function resulted in values of 31.0% (+/-14.0) and 28.3% (+/-14.0), respectively. CONCLUSIONS: Using a closed-system model with a fixed SP isotope effect may significantly overestimate the N2O reduction effect on SP values, especially when N2O reduction rates are high. This is probably due to soil inhomogeneity and can be compensated for by the application of a dynamic apparent NIE function, which takes the variable reduction rates in soil micropores into account. PMID- 26842584 TI - Fragmentation and ion mobility properties of negative ions from N-linked carbohydrates: Part 7. Reduced glycans. AB - RATIONALE: Negative ion collision-induced dissociation (CID) spectra of released N-glycans provide very informative structural information relating to branching patterns and location of residues such as fucose. For some structural studies, particularly those involving chromatography, glycans are often reduced to avoid production of multiple peaks from alpha- and beta-anomers. We examined the effect of reduction on the production of diagnostic fragment ions and on the ion mobility properties of N-glycans. METHODS: Released N-glycans from the glycoproteins bovine fetuin, ribonuclease B, chicken ovalbumin, and porcine thyroglobulin were reduced with sodium cyanoborohydride and both negative ion CID spectra and ion mobility properties of their phosphate adducts were examined with a Waters Synapt G2Si travelling-wave ion mobility mass spectrometer with electrospray sample introduction. Estimated collisional cross sections were measured with dextran as the calibrant, RESULTS: Fragment ions were similar to those from the unreduced glycans with the exception that the prominent (2,4) A cleavage ion from the reducing terminus was replaced by a prominent [M-H3 PO4](-) ion. Other ions arising from the chitobiose core were of lower relative abundance than those from the unreduced glycans. Estimated collisional cross sections were similar to those of the unreduced compounds but with symmetrical arrival time distribution (ATD) profiles, unlike those of the unreduced glycans whose peaks often contained prominent asymmetry. This observation showed that this asymmetry was due to anomer separation. CONCLUSIONS: Reduction of the reducing terminal GlcNAc residue resulted in fewer diagnostic ions from the chitobiose core but fragmentation of the remainder of the molecules generally paralleled that of the unreduced glycans. Thus, most structural information, with the exception of the linkage position of fucose on the core GlcNAc, was available. ATD peaks were symmetrical with the result that cross sections were more appropriate for data base searching than those from the non-reduced compounds where asymmetry produced lower precision in the measurement. PMID- 26842585 TI - Emerging drugs affecting skeletal muscle function and mitochondrial biogenesis - Potential implications for sports drug testing programs. AB - RATIONALE: A plethora of compounds potentially leading to drug candidates that affect skeletal muscle function and, more specifically, mitochondrial biogenesis, has been under (pre)clinical investigation for rare as well as more common diseases. Some of these compounds could be the object of misuse by athletes aiming at artificial and/or illicit and drug-facilitated performance enhancement, necessitating preventive and proactive anti-doping measures. METHODS: Early warnings and the continuous retrieval and dissemination of information are crucial for sports drug testing laboratories as well as anti-doping authorities, as they assist in preparation of efficient doping control analytical strategies for potential future threats arising from new therapeutic developments. Scientific literature represents the main source of information, which yielded the herein discussed substances and therapeutic targets, which might become relevant for doping controls in the future. Where available, mass spectrometric data are presented, supporting the development of analytical strategies and characterization of compounds possibly identified in human sports drug testing samples. RESULTS & CONCLUSIONS: Focusing on skeletal muscle and mitochondrial biogenesis, numerous substances exhibiting agonistic or antagonistic actions on different cellular 'control centers' resulting in increased skeletal muscle mass, enhanced performance (as determined with laboratory animal models), and/or elevated amounts of mitochondria have been described. Substances of interest include agonists for REV-ERBalpha (e.g. SR9009, SR9011, SR10067, GSK4112), sirtuin 1 (e.g. SRT1720, SRT2104), adenosine monophosphate-activated protein kinase (AMPK, e.g. AICAR), peroxisome proliferator-activated receptor (PPAR)delta (e.g. GW1516, GW0742, L165041), and inhibitory/antagonistic agents targeting the methionine-folate cycle (MOTS-c), the general control non-derepressible 5 (GCN5) acetyl transferase (e.g. CPTH2, MB-3), myostatin (e.g. MYO-029), the myostatin receptor (bimagrumab), and myostatin receptor ligands (e.g. sotatercept, ACE 031). In addition, potentially relevant drug targets were identified, e.g. with the sarcoplasmic transmembrane peptide myoregulin and the nuclear receptor corepressor 1 (NCOR-1). The antagonism of these has shown to result in substantially enhanced physical performance in animals, necessitating the monitoring of strategies such as RNA interference regarding these substances. Most drug candidates are of lower molecular mass and comprise non-natural compositions, facts which suggest approaches for their qualitative identification in doping control samples by mass spectrometry. Electrospray ionization/collision induced dissociation mass spectra of representatives of the aforementioned substances and selected in vitro derived phase-I metabolites support this assumption, and test methods for a subset of these have been recently established. Expanding the knowledge on analytical data will further facilitate the identification of such analytes and related compounds in confiscated material as well as sports drug testing specimens. PMID- 26842586 TI - Identification of protein adduction using mass spectrometry: Protein adducts as biomarkers and predictors of toxicity mechanisms. AB - The determination of protein-xenobiotic adducts using mass spectrometry is an emerging area which allows detailed understanding of the underlying mechanisms involved in toxicity. These approaches can also be used to reveal potential biomarkers of exposure or toxic response. The following review covers studies of protein adducts resulting from exposure to a wide variety of xenobiotics including organophosphates, polycyclic aromatic hydrocarbons, acetaminophen, alkylating agents and other related compounds. PMID- 26842587 TI - Quality control of oligonucleotide synthesis by means of matrix-assisted laser desorption/ionization linear time-of-flight mass spectrometry on a nanocoated disposable target. PMID- 26842589 TI - Histopathological analysis of anaplastic thyroid carcinoma cases with long-term survival: A report from the Anaplastic Thyroid Carcinoma Research Consortium of Japan. AB - The aim of this study was to clarify the histopathological features of anaplastic thyroid carcinoma in patients who achieved long-term survival. We reviewed 88 anaplastic thyroid carcinoma cases in which the patient survived less than 3 months (short-term survival), and 68 anaplastic thyroid carcinoma cases in which the patient survived more than one year (long-term survival) from the database of the Anaplastic Thyroid Carcinoma Research Consortium of Japan. We examined these cases both histologically and immunohistochemically. Six (6.8%) short-term survival cases and 27 (39.7%) long-term survival cases were considered not to be anaplastic thyroid carcinoma after central review. Of these, 12 were revised to papillary carcinoma with squamous cell carcinoma. In cases without chemotherapy, long-term survival was significantly more common if there was a pre-existing tumor, epithelial growth, or lymphocytic infiltration, and short-term survival was more common if neutrophilic infiltration was present. In cases with chemotherapy, long-term survival was significantly more common if epithelial growth or a squamous cell carcinoma component was present, whereas short-term survival was more common in cases with rhabdoid cells. Immunohistochemical results were not related to survival. Some long-term survival cases showed histological findings other than those typically associated with anaplastic thyroid carcinoma. The presence of a pre-existing tumor, epithelial growth, a squamous cell carcinoma component, no neutrophilic infiltration and lymphocytic infiltration may therefore be favorable prognostic factors in anaplastic thyroid carcinoma. PMID- 26842590 TI - Simvastatin rescues homocysteine-induced apoptosis of osteocytic MLO-Y4 cells by decreasing the expressions of NADPH oxidase 1 and 2. AB - Clinical studies have shown that hyperhomocysteinemia is associated with bone fragility. Homocysteine (Hcy) induces apoptosis of osteoblastic cell lineage by increasing oxidative stress, which may contribute to Hcy-induced bone fragility. Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, ameliorate oxidative stress by regulating oxidant and anti-oxidant enzymes. However, the effects of statins on Hcy-induced apoptosis of osteocytes are unknown. This study was thus aimed to investigate whether or not statins prevent Hcy-induced apoptosis of osteocytic MLO-Y4 cells and regulate NADPH oxidase (Nox) expression. TUNEL staining showed that 5 mM Hcy induced apoptosis of MLO-Y4 cells, and that co-incubation of 10(-9) or 10(-8) M simvastatin significantly suppressed the apoptotic effect. Moreover, we confirmed the beneficial effect of simvastatin against Hcy's apoptotic effect by using a DNA fragment ELISA assay. However, TUNEL staining showed no significant effects of pravastatin, a hydrophilic statin, on the Hcy-induced apoptosis. Real-time PCR showed that Hcy increased the mRNA expressions of Nox1 and Nox2, whereas simvastatin inhibited the stimulation of Nox1 and Nox2 expressions by Hcy. In contrast, neither Hcy nor simvastatin had any effect on Nox4 expression. These findings indicate that simvastatin prevents the detrimental effects of Hcy on the apoptosis of osteocytes by regulating the expressions of Nox1 and Nox2, suggesting that statins may be beneficial for preventing Hcy-induced osteocyte apoptosis and the resulting bone fragility. PMID- 26842591 TI - Reference intervals of thyroid hormones in a previously iodine-deficient but presently more than adequate area of Western China: a population-based survey. AB - The aim of our study is to establish the reference intervals (RIs) of thyroid hormones in a previously iodine-deficient area but presently more than iodine adequate area of Western China, and also to investigate the factors which affect thyroid function. The cross-sectional study conducted in Xi'an, was based on 2007 2008 China National Diabetes and Metabolic Disorders Survey. Among 1286 participating adults, 717 were finally included as reference population. Thyrotropin (TSH), total triiodothyronine (T3), free triiodothyronine (FT3), total thyroxine (T4), free thyroxine (FT4), thyroperoxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) were measured. Thyroid ultrasound examination was also performed. The present study established the new RIs of serum TSH (0.43-5.51 mIU/L), FT4 (11.0-20.4 pmol/L), FT3 (3.63-5.73 pmol/L), T4 (67.8-157 mmol/L) and T3 (1.08-2.20 mmol/L), which were different from the data provided by the manufacturers. Significant differences among all the age groups were observed in FT3, but neither in TSH nor in FT4. The TSH levels in adults with pathologic ultrasonography results or positive thyroid autoantibody were significantly higher than those in reference adults. Our present results provide valuable references for the diagnosis of thyroid diseases in population of Western China. Considering that most inland areas of China have faced the challenge of the transition from iodine deficiency to adequacy or more than adequacy, we recommend physicians utilize our RIs to determine thyroid diseases in the similar areas with Xi'an in China. PMID- 26842588 TI - Early diagnosis of Alzheimer's disease from elevated olfactory mucosal miR-206 level. AB - MicroRNA-206, which suppresses the expression of brain-derived neurotrophic factor, is known to be elevated in the brains of Alzheimer's disease (AD) patients. We performed intranasal biopsy of the olfactory epithelia of early dementia patients (n = 24) and cognitively healthy controls (n = 9). Patients with significant depression (n = 8) were analyzed separately, as their cognitive impairments were thought to be caused by their depression. Real-time PCR was performed on the biopsied tissues. The relative microRNA-206 level exhibited a 7.8-fold increase (P = 0.004) in the mild cognitive impairment group (CDR 0.5; n = 13) and a 41.5-fold increase (P < 0.001) in the CDR 1 group (n = 11). However, this level was not increased in the depression group, even in those with cognitive decline. Using the optimal cutoff value, the sensitivity/specificity for diagnosing CDR 0.5 and CDR 1 dementia were 87.5%/94.1% and 90.9%/93.3%, respectively. In ROC analysis, the AUCs were 0.942 and 0.976 in the CDR 0.5 and CDR 1 groups, respectively. The olfactory mucosal microRNA-206 level and cognitive assessment scores were significantly correlated in the non-depressed subjects with cognitive impairment. In conclusion, the olfactory mucosal microRNA 206 level can be easily measured, and it can be utilized as an excellent biomarker for the diagnosis of early AD, including mild cognitive impairment. PMID- 26842592 TI - Detrimental effects of high-fat diet loading on vascular endothelial function and therapeutic efficacy of ezetimibe and statins in patients with type 2 diabetes. AB - Several recent reports from large clinical trials have described the role of postprandial hyperlipidemia in the onset of atherosclerosis. In this pilot study, the effects of postprandial lipid abnormalities induced by high-fat diet loading on vascular endothelial function in type 2 diabetes were investigated and the effects of ezetimibe and statins on endothelial function were compared. In 20 patients in Study 1, peripheral arterial tonometry tests were performed before and 4h after loading to measure the reactive hyperemia index (RHI). In Study 2, the same patients were randomly allocated to ezetimibe or rosuvastatin. After 1 week of treatment, loading tests were conducted in the same manner. In Study 1, the RHI decreased from 1.86 to 1.60. There were no significant correlations between changes in RHI and the area under the curve (AUC) or coefficient of variation (CV) of each metabolic marker. In Study 2, ezetimibe treatment resulted in a significant improvement in RHI. The two drugs had comparable effects on changes in AUC. There were no significant correlations between changes in RHI and changes in AUC or changes in CV. When age, sex, drug, hemoglobin A1c, and changes in each lipid were evaluated as independent variables with RHI improvement as the dependent variable, drug differences were found to exert the greatest effect on RHI improvement using a stepwise procedure. The results of this study suggest that the progression of atherosclerosis is due to abnormalities in postprandial lipid metabolism and that ezetimibe can potentially inhibit the aggravation of vascular endothelial dysfunction after high-fat diet loading. PMID- 26842593 TI - Optimization of the Expression of Human Aldehyde Oxidase for Investigations of Single-Nucleotide Polymorphisms. AB - Aldehyde oxidase (AOX1) is an enzyme with broad substrate specificity, catalyzing the oxidation of a wide range of endogenous and exogenous aldehydes as well as N heterocyclic aromatic compounds. In humans, the enzyme's role in phase I drug metabolism has been established and its importance is now emerging. However, the true physiologic function of AOX1 in mammals is still unknown. Further, numerous single-nucleotide polymorphisms (SNPs) have been identified in human AOX1. SNPs are a major source of interindividual variability in the human population, and SNP-based amino acid exchanges in AOX1 reportedly modulate the catalytic function of the enzyme in either a positive or negative fashion. For the reliable analysis of the effect of amino acid exchanges in human proteins, the existence of reproducible expression systems for the production of active protein in ample amounts for kinetic, spectroscopic, and crystallographic studies is required. In our study we report an optimized expression system for hAOX1 in Escherichia coli using a codon-optimized construct. The codon-optimization resulted in an up to 15 fold increase of protein production and a simplified purification procedure. The optimized expression system was used to study three SNPs that result in amino acid changes C44W, G1269R, and S1271L. In addition, the crystal structure of the S1271L SNP was solved. We demonstrate that the recombinant enzyme can be used for future studies to exploit the role of AOX in drug metabolism, and for the identification and synthesis of new drugs targeting AOX when combined with crystallographic and modeling studies. PMID- 26842594 TI - CYP267A1 and CYP267B1 from Sorangium cellulosum So ce56 are Highly Versatile Drug Metabolizers. AB - The guidelines of the Food and Drug Administration and International Conference on Harmonization have highlighted the importance of drug metabolites in clinical trials. As a result, an authentic source for their production is of great interest, both for their potential application as analytical standards and for required toxicological testing. Since we have previously shown promising biotechnological potential of cytochromes P450 from the soil bacterium Sorangium cellulosum So ce56, herein we investigated the CYP267 family and its application for the conversion of commercially available drugs including nonsteroidal anti inflammatory, antitumor, and antihypotensive drugs. The CYP267 family, especially CYP267B1, revealed the interesting ability to convert a broad range of substrates. We established substrate-dependent extraction protocols and also optimized the reaction conditions for the in vitro experiments and Escherichia coli-based whole-cell bioconversions. We were able to detect activity of CYP267A1 toward seven out of 22 drugs and the ability of CYP267B1 to convert 14 out of 22 drugs. Moderate to high conversions (up to 85% yield) were observed in our established whole-cell system using CYP267B1 and expressing the autologous redox partners, ferredoxin 8 and ferredoxin-NADP(+) reductase B. With our existing setup, we present a system capable of producing reasonable quantities of the human drug metabolites 4'-hydroxydiclofenac, 2-hydroxyibuprofen, and omeprazole sulfone. Due to the great potential of converting a broad range of substrates, wild-type CYP267B1 offers a wide scope for the screening of further substrates, which will draw further attention to future biotechnological usage of CYP267B1 from S. cellulosum So ce56. PMID- 26842595 TI - In Vitro-In Vivo Extrapolation Scaling Factors for Intestinal P-glycoprotein and Breast Cancer Resistance Protein: Part II. The Impact of Cross-Laboratory Variations of Intestinal Transporter Relative Expression Factors on Predicted Drug Disposition. AB - Relative expression factors (REFs) are used to scale in vitro transporter kinetic data via in vitro-in vivo extrapolation linked to physiologically based pharmacokinetic (IVIVE-PBPK) models to clinical observations. Primarily two techniques to quantify transporter protein expression are available, immunoblotting and liquid chromatography-tandem mass spectrometry. Literature collated REFs ranged from 0.4 to 5.1 and 1.1 to 90 for intestinal P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), respectively. The impact of using human jejunum-Caco-2 REFs for P-gp (REFiP-gp) and BCRP (REFiBCRP), generated from the same samples and using different proteomic methodologies from independent laboratories, on PBPK outcomes was assessed. A 5-fold decrease in REFiP-gp for a single oral dose of digoxin resulted in a 1.19- and 1.31-fold higher plasma area under the curve and Cmax, respectively. All generated REFiP-gp values led to simulated digoxin Cmax values within observed ranges; however, combining kinetic data generated from a different laboratory with the 5-fold lower REFiP-gp could not recover a digoxin-rifampicin drug-drug interaction, emphasizing the necessity to obtain transporter-specific kinetic estimates and REFs from the same in vitro system. For a theoretical BCRP compound, with absorption taking place primarily in the jejunum, a decrease in the REFiBCRP from 2.22 (University of Manchester) to 1.11 (Bertin Pharma) promoted proximal intestinal absorption while delaying tmax 1.44-fold. Laboratory-specific differences in REF may lead to different IVIVE-PBPK outcomes. To understand the mechanisms underlying projected pharmacokinetic liabilities, it is important to assess the potential impact of bias on the generation of REFs on an interindividual basis within a target population. PMID- 26842596 TI - Mechanistic Modeling of Pitavastatin Disposition in Sandwich-Cultured Human Hepatocytes: A Proteomics-Informed Bottom-Up Approach. AB - Isolated human hepatocytes are commonly used to predict transporter-mediated clearance in vivo. Such predictions, however, do not provide estimations of transporter contributions and consequently do not allow predictions of the outcome resulting from a change in the activity of a certain transporter, for example, by inhibition or a genetic variant with reduced function. Pitavastatin is a drug that is heavily dependent on hepatic transporters for its elimination, and it is excreted mainly as unchanged drug in the bile. For this reason, pitavastatin was used as a model drug to demonstrate the applicability of a bottom-up approach to predict transporter-mediated disposition in sandwich cultured human hepatocytes (SCHHs), allowing for the estimation of transporter contributions. Transport experiments in transfected human embryonic kidney cells (HEK293 cell lines) and inverted membrane vesicles overexpressing each of the relevant transport proteins were used to generate parameter estimates for the mechanistic model. By adjusting for differences in transporter abundance between the in vitro systems and individual SCHH batches, the model successfully predicted time profiles of medium and intracellular accumulation. Our predictions of pitavastatin bile accumulation could not be confirmed, however, because of a very low biliary excretion of pitavastatin in relation to the hepatic uptake in our SCHHs. This study is, to our knowledge, the first to successfully simulate transporter-mediated processes in a complex system such as SCHHs at the level of individual transport proteins using a bottom-up approach. PMID- 26842597 TI - Production of Butyrate from Lactate by a Newly Isolated Clostridium sp. BPY5. AB - Lactate-utilizing bacteria play important roles in the production of Chinese strong-flavored liquor (CSFL). However, the identity of these bacteria and their lactate-utilizing properties are largely unknown. Here, a lactate-utilizing, butyrate-producing bacterium BPY5 was isolated from an old fermentation pit for CSFL production. The isolate represented a novel species belonging to Clostridium cluster XIVa of family Lachnospiraceae based on phylogenetic analysis using 16S rRNA gene sequences. Strain BPY5 could ferment lactate into butyrate as the major metabolic product. Butyrate was significantly formed at initial lactate concentration from 66 to 104 mM, but substantially declined when initial lactate exceeded 133 mM. At initial lactate concentration of 66 mM, lactate conversion was independent on initial pH from 5.5 to 7.0, but the conversion was completely inhibited when pH dropped below 4.8. Nevertheless, the inhibition on lactate conversion was largely relieved by the addition of acetate, suggesting that exogenous acetate could enhance lactate conversion at low pH condition. Additionally, lactate in CSFL-brewing wastewater was dramatically removed when inoculated with strain BPY5. These results implicate that the isolate may be applied for the industrial production of butyrate or the recovery of butyrate from lactate-containing wastewater. PMID- 26842598 TI - Production of Omega-3 Fatty Acid Ethyl Esters from Menhaden Oil Using Proteus vulgaris Lipase-Mediated One-Step Transesterification and Urea Complexation. AB - An organic solvent-stable lipase from Proteus vulgaris K80 was used to produce the omega-3 polyunsaturated fatty acid ethyl esters (omega-3 PUFA EEs). First, the lyophilized recombinant lipase K80 (LyoK80) was used to perform the transesterification reaction of menhaden oil and ethanol. LyoK80 produced the omega-3 PUFA EEs with a conversion yield of 82 % in the presence of 20 % water content via a three-step ethanol-feeding process; however, in a non-aqueous condition, LyoK80 produced only a slight amount of the omega-3 PUFA EEs. To enhance its reaction properties, the lipase K80 was immobilized on a hydrophobic bead to derive ImmK80; the biochemical properties and substrate specificity of ImmK80 are similar to those of LyoK80. ImmK80 was then used to produce omega-3 PUFA EEs in accordance with the same transesterification reaction. Unlike LyoK80, ImmK80 achieved a high omega-3 PUFA EE conversion yield of 86 % under a non aqueous system via a one-step ethanol-feeding reaction. The omega-3 PUFA EEs were purified up to 92 % using a urea complexation method. PMID- 26842599 TI - ROCK1 Induces Endothelial-to-Mesenchymal Transition in Glomeruli to Aggravate Albuminuria in Diabetic Nephropathy. AB - Endothelial-to-mesenchymal transition (EndMT) can cause loss of tight junctions, which in glomeruli are associated with albuminuria. Here we evaluated the role of EndMT in the development of albuminuria in diabetic nephropathy (DN). We demonstrated that EndMT occurs in the glomerular endothelium of patients with DN, showing by a decrease in CD31 but an increase in alpha-SMA expression. In glomeruli of db/db mice, there was an increased ROCK1 expression in the endothelium plus a decreased CD31-positive cells. Cultured glomerular endothelial cells (GEnCs) underwent EndMT when stimulated by 30 mM glucose, and exhibited increased permeability. Meanwhile, they showed a higher ROCK1 expression and activation. Notably, inhibition of ROCK1 largely blocked EndMT and the increase in endothelial permeability under this high-glucose condition. In contrast, overexpression of ROCK1 induced these changes. Consistent alterations were observed in vivo that treating db/db mice with the ROCK1 inhibitor, fasudil, substantially suppressed the expression of alpha-SMA in the glomerular endothelium, and reduced albuminuria. Thus we conclude that ROCK1 is induced by high glucose and it stimulates EndMT, resulting in increased endothelial permeability. Inhibition of ROCK1 could be a therapeutic strategy for preventing glomerular endothelial dysfunction and albuminuria in developing DN. PMID- 26842600 TI - Intracerebral Injection of Metal-Binding Domain of Abeta Comprising the Isomerized Asp7 Increases the Amyloid Burden in Transgenic Mice. AB - Intracerebral or intraperitoneal injections of brain extracts from the Alzheimer's disease patients result in the acceleration of cerebral beta amyloidosis in transgenic mice. Earlier, we have found that intravenous injections of synthetic full-length amyloid-beta (Abeta) comprising the isomerized Asp7 trigger cerebral beta-amyloidosis. In vitro studies have shown that isomerization of Asp7 promotes zinc-induced oligomerization of the Abeta metal-binding domain (Abeta1-16). Here we report that single intracerebral injection of the peptide Abeta1-16 with isomerized Asp7 (isoAbeta1-16) but not the injection of Abeta1-16 significantly increases amyloid burden in 5XFAD transgenic mice. Our results provide evidence for a role of isoAbeta1-16 as a minimal seeding agent of Abeta aggregation in vivo. PMID- 26842601 TI - Stereological study of the effects of maternal diabetes on cerebellar cortex development in rat. AB - Diabetes during pregnancy is associated with the deficits in balance and motor coordination and altered social behaviors in offspring. In the present study, we have investigated the effect of maternal diabetes and insulin treatment on the cerebellar volume and morphogenesis of the cerebellar cortex of rat neonates during the first two postnatal weeks. Sprague Dawley female rats were maintained diabetic from a week before pregnancy through parturition. At the end of pregnancy, the male offspring euthanized on postnatal days (P) 0, 7, and 14. Cavalieri's principle and fractionator methods were used to estimate the cerebellar volume, the thickness and the number of cells in the different layers of the cerebellar cortex. In spite of P0, there was a significant reduction in the cerebellar volume and the thickness of the external granule, molecular, and internal granule layers between the diabetic and the control animals. In diabetic group, the granular and purkinje cell densities were increased at P0. Moreover, the number of granular and purkinje cells in the cerebellum of diabetic neonates was reduced in comparison with the control group at P7 and P14. There were no significant differences in either the volume and thickness or the number of cells in the different layers of the cerebellar cortex between the insulin-treated diabetic group and controls. Our data indicate that diabetes in pregnancy disrupts the morphogenesis of cerebellar cortex. This dysmorphogenesis may be part of the cascade of events through which diabetes during pregnancy affects motor coordination and social behaviors in offspring. PMID- 26842603 TI - Atrial fibrillation associated with acute pancreatitis: a retrospective cohort study in Taiwan. AB - BACKGROUND: There is little data on the relationship between atrial fibrillation and acute pancreatitis. The aim of this study was to evaluate whether atrial fibrillation is associated with acute pancreatitis. METHODS: This retrospective cohort study analyzed the database of the Taiwan National Health Insurance Program from 2000 to 2010. There were 8,981 subjects aged 20-84 with newly diagnosed atrial fibrillation as the atrial fibrillation group and 26,643 sex- and age-matched, randomly selected subjects without atrial fibrillation as the non-atrial fibrillation group. We used the multivariable Cox proportional hazards regression model to measure the hazard ratio (HR) and 95% confidence interval (CI) for acute pancreatitis risk associated with atrial fibrillation and other comorbidities. RESULTS: The crude incidence rates of acute pancreatitis were 3.07 per 1,000 person-years in the atrial fibrillation group and 2.03 per 1,000 person years in the non-atrial fibrillation group (incidence rate ratio 1.51, 95% CI 1.40, 1.63). After controlling for potential confounding factors, the adjusted HR of acute pancreatitis was 1.46 for the atrial fibrillation group, as compared with the non-atrial fibrillation group (95% CI 1.18, 1.80). In further analysis, even in the absence of alcohol-related disease and biliary stone, the adjusted HR of acute pancreatitis was 1.62 for the atrial fibrillation group, as compared with the non-atrial fibrillation group (95% CI 1.24, 2.12). CONCLUSIONS: Atrial fibrillation is associated with acute pancreatitis in the Taiwanese population, even in the absence of alcohol-related disease and biliary stone. Further research is necessary to explore the pathogenesis underlying the relationship between atrial fibrillation and acute pancreatitis. PMID- 26842604 TI - UK is safe from Zika virus and is helping towards a vaccine, MPs hear. PMID- 26842602 TI - Metabolic engineering of terpene biosynthesis in plants using a trichome-specific transcription factor MsYABBY5 from spearmint (Mentha spicata). AB - In many aromatic plants including spearmint (Mentha spicata), the sites of secondary metabolite production are tiny specialized structures called peltate glandular trichomes (PGT). Having high commercial values, these secondary metabolites are exploited largely as flavours, fragrances and pharmaceuticals. But, knowledge about transcription factors (TFs) that regulate secondary metabolism in PGT remains elusive. Understanding the role of TFs in secondary metabolism pathway will aid in metabolic engineering for increased yield of secondary metabolites and also the development of new production techniques for valuable metabolites. Here, we isolated and functionally characterized a novel MsYABBY5 gene that is preferentially expressed in PGT of spearmint. We generated transgenic plants in which MsYABBY5 was either overexpressed or silenced using RNA interference (RNAi). Analysis of the transgenic lines showed that the reduced expression of MsYABBY5 led to increased levels of terpenes and that overexpression decreased terpene levels. Additionally, ectopic expression of MsYABBY5 in Ocimum basilicum and Nicotiana sylvestris decreased secondary metabolite production in them, suggesting that the encoded transcription factor is probably a repressor of secondary metabolism. PMID- 26842605 TI - The importance of protection glasses during neuroangiographies: A study on radiation exposure at the lens of the primary operator. AB - BACKGROUND: In interventional neuroradiology, few operators routinely use radiation protection glasses. Moreover, in most centers, radiation dose data only accounts for whole body dose without specific information on lens dose. In 2012, the International Commission on Radiological Protection advised that the threshold limit value for the lens should be 20 mSv/year instead of the previous 150 mSv/year limit. The purpose of this study was to compare the radiation dose in the operator's lens during real diagnostic and interventional neuroangiographies, either using or without lead protection glasses. METHODS: Using the Educational Direct Dosimeter (EDD30 dosimeter), accumulated radiation dose in the lens was measured in 13 neuroangiographies: seven diagnostic and six interventional. Operators with and without radiation protection glasses were included and the sensor was placed near their left eye, closest to the radiation beam. RESULTS: Without glasses, the corrected mean dose of radiation in the lens was 8.02 uSv for diagnostic procedures and 168.57 uSv for interventional procedures. Using glasses, these values were reduced to 1.74 uSv and 33.24 uSv, respectively. CONCLUSION: Considering 20 mSv as the suggested annual limit of equivalent dose in the lens, neuroradiologists may perform up to 2,494 diagnostic procedures per year without protecting glasses, a number that increases to 11,494 when glasses are used consistently. Regarding intervention, a maximum of 119 procedures per year is advised if glasses are not used, whereas up to 602 procedures/year may be performed using this protection. Therefore, neuroradiologists should always wear radiation protection glasses. PMID- 26842607 TI - 'Donut' basilar aneurysm with brainstem compression: Treatment using a flow diverting stent. AB - Partially thrombosed aneurysms with circular flow dynamics around central thrombus pose a therapeutic dilema. We demonstrate the successful treatment of a patient with a large basilar donut aneurysm with a flow diverting stent without the use of embolisation coils in order to obviate the risk of further brainstem compression. PMID- 26842606 TI - Maximizing efficiency and diagnostic accuracy triage of acute stroke patients: A case-control study. AB - BACKGROUND: Recent data have demonstrated that mechanical thrombectomy (MT) is beneficial for patients presenting within zero to six hours of symptom onset after stroke. However, transferring all patients with possible strokes for endovascular therapy and MT would be inefficient and costly. We conducted a case control study to identify a subset of the National Institutes of Health Stroke Scale (NIHSS) to identify patients with large-vessel occlusion (LVO) to a high degree of specificity, in order to select those patients for whom transfer is most appropriate. METHODS: Acute code stroke alerts presenting to a comprehensive stroke center from 2012 to 2013 (779) and corresponding NIHSS were collected. All patients had vascular imaging and 125 demonstrated LVO (cases) and were compared to 272 small-vessel strokes and stroke mimics (controls). Demographics of both groups and modified receiver operating characteristic (ROC) curves were generated for each combination of three NIHSS items to optimize specificity of LVO for those who would benefit from MT. RESULTS: The average NIHSS of cases was higher than controls (12.5 vs. 6.5, p < 0.0001). The subset of three NIHSS items with the largest modified AUC (optimized for specificity) was maximum "Arm," "Sensory," and "Extinction." Using a cutoff of seven out of a total 10 possible points, the sum score for these items has 90.2% specificity and 16.0% sensitivity for LVO. CONCLUSION: We present a validated three-question subset of the NIHSS for those who would benefit from MT with a high degree of specificity. PMID- 26842608 TI - Detection of wall and neck calcification of unruptured intracranial aneurysms with flat-detector computed tomography. AB - OBJECT: Microsurgical clipping is a widely used surgical technique in intracranial aneurysm treatment. It can be difficult in large sized aneurysms, and those with wide necks, thick walls and calcification located in the vicinity of the neck. This study reviewed calcification of the intracranial aneurysm wall and its relation to patient age, gender, location and size of the aneurysm. A possible cut-off value after which the aneurysm calcification rate increases was also investigated to classify patients' risk factors for microclipping. METHODS: A retrospective review of all unruptured intracranial aneurysms that underwent digital subtraction angiography at a single centre was performed. Flat-detector computed tomography images of the aneurysm were reviewed for aneurysm location, size and calcification. The independent samples t test and chi(2) test were used to show the relation between aneurysm wall calcification and patient age, gender, aneurysm localisation and size. RESULTS: None of the reviewed factors were statistically significantly related to aneurysm calcification except aneurysm size (P < 0.01). Receiver operating characteristic curves showed aneurysms greater than 10.5 mm could be predicted to be calcified with a sensitivity of 80% and specificity of 63%. CONCLUSION: In this study, the presence of calcification was related to aneurysm size. Larger aneurysms were more likely to be calcified. Aneurysms greater than 10.5 mm should be further investigated with a modality such as flat-detector computed tomography to show the calcification in detail, especially if microclipping is considered. PMID- 26842609 TI - Embolization of a congenital arteriovenous fistula of the internal maxillary artery: A case report and review of the literature. AB - A 13 year-old girl with a congenital carotid-jugular fistula presented with a pulsatile mass and a thrill on the left side of her neck. Angiography showed a fistula between the left internal maxillary artery and the jugular vein. The patient underwent coil embolization using a transarterial balloon-assisted technique and one week later, a transvenous approach. The fistula was completely obliterated, and the patient's symptoms resolved. PMID- 26842610 TI - Stent treatment for basilar artery dissection: A single-center experience of 21 patients. AB - Basilar artery dissection is a rare disease with high morbidity and mortality. No well-established management strategy exists for this lesion. Endovascular reconstructive therapy using stents (with or without coiling) may be the optimum strategy.We describe our center's experience for this treatment strategy in 21 patients with basilar artery dissection from January 2009 to July 2014 (17 men, four women; age range, 18-70 years; median age, 56 years). We divided patients into two groups: Group 1 patients received stent-assisted coiling treatment, and Group 2 patients received stent-only treatment. Pre-treatment, peri-operation and follow-up evaluation were investigated for complications, clinical outcome and angiographic results. The median follow-up time was 20 months (range, 3-67 months).All patients were treated endovascularly by stent-assisted coiling (14 patients) or stent only (seven patients). Immediate angiography showed: in Group 1, five of 14 lesions were completely occluded, five were partially occluded, four revealed retention of contrast media; in Group 2, all patients (seven of seven) had contrast retention. At the follow-up visit (median seven months, 3-29 months), the aneurysms were angiographically improved in five of 13 patients in Group 1 compared with immediately post-operation, while six of sevenimproved in Group 2. Five patients (all in Group 1) had ischemic or hemorrhage peri-operation complications. Long-term good clinical outcomes (modified Rankin Scale score (mRS) <= 2) were achieved in all patients except three death cases (two in Group1, one in Group 2).In our experience, endovascular reconstructive therapy using stents (with or without coiling) for basilar artery dissection is effective and safe. Stent-only treatment seems have a better safety profile during the peri operation period. PMID- 26842611 TI - Histopathological findings following pipeline embolization in a human cerebral aneurysm at the basilar tip. AB - We report histopathological findings from a human cerebral aneurysm following treatment with a flow diverter. A 75-year-old male underwent flow diversion treatment (Pipeline Embolization Device (PED)) and coil embolization for treatment of an aneurysm at the basilar tip. At four months, angiography showed complete aneurysm occlusion; at 12 months angiography demonstrated that the aneurysm had reopened. The patient expired from brainstem compression. The aneurysm cavity was primarily filled with unorganized thrombus. Thick, interrupted neointima crossed the neck interface indicating blood flow into aneurysm through small channels. Along the parent artery the PED was covered by neointima having a measured thickness of 0.19 +/- 0.01 mm; the maximal stenosis of the proximal parent artery was 27%. The perforating arteries that were crossed by the PED remained patent. Findings in this human case are similar to those in the elastase-induced aneurysms in rabbits. PMID- 26842612 TI - Spatial and seasonal variations of isoprene secondary organic aerosol in China: Significant impact of biomass burning during winter. AB - Isoprene is a substantial contributor to global secondary organic aerosol (SOA). The formation of isoprene SOA (SOAI) is highly influenced by anthropogenic emissions. Currently, there is rare information regarding SOAI in polluted regions. In this study, one-year concurrent observation of SOAI tracers was undertaken at 12 sites across China for the first time. The tracers formed from the HO2-channel exhibited higher concentrations at rural sites, while the tracer formed from the NO/NO2-channel showed higher levels at urban sites. 3 Methyltetrahydrofuran-3,4-diols exhibited linear correlations with their ring opening products, C5-alkenetriols. And the slopes were steeper in the southern China than the northern China, indicating stronger ring-opening reactions there. The correlation analysis of SOAI tracers with the factor determining biogenic emission and the tracer of biomass burning (levoglucosan) implied that the high level of SOAI during summer was controlled by biogenic emission, while the unexpected increase of SOAI during winter was largely due to the elevated biomass burning emission. The estimated secondary organic carbon from isoprene (SOCI) exhibited the highest levels in Southwest China. The significant correlations of SOCI between paired sites implied the regional impact of SOAI in China. Our findings implicate that isoprene origins and SOAI formation are distinctive in polluted regions. PMID- 26842613 TI - Forecasting paediatric malaria admissions on the Kenya Coast using rainfall. AB - BACKGROUND: Malaria is a vector-borne disease which, despite recent scaled-up efforts to achieve control in Africa, continues to pose a major threat to child survival. The disease is caused by the protozoan parasite Plasmodium and requires mosquitoes and humans for transmission. Rainfall is a major factor in seasonal and secular patterns of malaria transmission along the East African coast. OBJECTIVE: The goal of the study was to develop a model to reliably forecast incidences of paediatric malaria admissions to Kilifi District Hospital (KDH). DESIGN: In this article, we apply several statistical models to look at the temporal association between monthly paediatric malaria hospital admissions, rainfall, and Indian Ocean sea surface temperatures. Trend and seasonally adjusted, marginal and multivariate, time-series models for hospital admissions were applied to a unique data set to examine the role of climate, seasonality, and long-term anomalies in predicting malaria hospital admission rates and whether these might become more or less predictable with increasing vector control. RESULTS: The proportion of paediatric admissions to KDH that have malaria as a cause of admission can be forecast by a model which depends on the proportion of malaria admissions in the previous 2 months. This model is improved by incorporating either the previous month's Indian Ocean Dipole information or the previous 2 months' rainfall. CONCLUSIONS: Surveillance data can help build time-series prediction models which can be used to anticipate seasonal variations in clinical burdens of malaria in stable transmission areas and aid the timing of malaria vector control. PMID- 26842614 TI - Foodomics study on the effects of extracellular production of hydrogen peroxide by rosemary polyphenols on the anti-proliferative activity of rosemary polyphenols against HT-29 cells. AB - A number of studies have demonstrated a strong association between the antioxidant properties of rosemary polyphenols and their chemoprotective activity. However, the prooxidant effects of rosemary polyphenols have been rarely reported. In this work, a foodomics study is performed to investigate the in vitro autooxidation of carnosic acid (CA), carnosol (CS) and a polyphenol enriched rosemary extract (SC-RE) in cell culture conditions. The results revealed that rosemary polyphenols autooxidation in culture medium generated H2 O2 at different rates. Generated H2 O2 levels by SC-RE and CA, but not CS, were correlated with intracellular reactive oxygen species (ROS) generation in HT-29 cells, and were partially involved in their anti-proliferative effect in this cell line. These compounds also induced different effects on glutathione metabolism. Results also indicated that high extracellular H2 O2 concentrations, resulting of using high (45 MUg/mL) SC-RE concentration in culture media, exerted some artifactual effects related with cell cycle, but they did not influence the expression of relevant molecular biomarkers of stress. PMID- 26842618 TI - Probing organic ligands and their binding schemes on nanocrystals by mass spectrometric and FT-IR spectroscopic imaging. AB - We report an analysis method to identify conjugated ligands and their binding states on semiconductor nanocrystals based on their molecular information. Surface science techniques, such as time-of-flight secondary-ion mass spectrometry (ToF-SIMS) and FT-IR spectroscopy, are adopted based on the micro aggregated sampling method. Typical trioctylphosphine oxide-based synthesis methods of CdSe/ZnS quantum dots (QDs) have been criticized because of the peculiar effects of impurities on the synthesis processes. Because the ToF-SIMS technique provides molecular composition evidence on the existence of certain ligands, we were able to clearly identify n-octylphosphonic acid (OPA) as a surface ligand on CdSe/ZnS QDs. Furthermore, the complementary use of the ToF SIMS technique with the FT-IR technique could reveal the OPA ligands' binding state as bidentate complexes. PMID- 26842615 TI - Low circulating pentraxin 3 levels in pregnancy is associated with gestational diabetes and increased apoB/apoA ratio: a 5-year follow-up study. AB - BACKGROUND: Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life. Pentraxin 3 (PTX3) is an essential component of innate immunity and independently associated with the risk of developing vascular events. The aim of the study was to examine the relationships between GDM, cardiovascular risk, and plasma PTX3 in pregnancy and at 5 years after the index pregnancy. METHODS: This population-based prospective cohort included 300 women who had an oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT was repeated along with dual-energy x-ray absorptiometry, lipid analysis, and pulse wave velocity analysis. Fasting PTX3 levels were measured four times during pregnancy and at follow-up. RESULTS: PTX3 levels were lower early in pregnancy and at 5 years follow-up in women who developed GDM. PTX3 levels throughout pregnancy were associated with body mass index. Low PTX3 levels in early pregnancy were predictive of an increased apoB/apoA ratio at 5-year follow-up. PTX3 at 5-year follow-up was inversely correlated with multiple metabolic risk factors for CVD, including body composition, arterial stiffness, dyslipidemia and previous GDM. CONCLUSIONS: Our results show that low plasma concentration of PTX3 in early pregnancy is associated with subsequent development of GDM and with an enhanced risk for CVD as estimated by an elevated apoB/apoA ratio at 5 years postpartum. PMID- 26842619 TI - The expression of MMP-14 and microRNA-410 in FFPE tissues of human endometrial adenocarcinoma. AB - Endometrial cancer (EC) is the most common gynecological malignancy in Europe and North America. It is classified into two types exhibiting different characteristics and prognosis. Type I is an estrogen-dependent tumor, histologically classified as low grade and low stage, usually with an excellent prognosis. Type II EC is unrelated to estrogen stimulation and is characterized by a poor prognosis. MicroRNAs (miRNAs, miRs) are small non-coding RNA polynucleotides that regulate gene expression post-transcriptionally. Various dysregulations in microRNA expression are often considered to have an impact on the diagnosis, prognosis and overall survival in patients diagnosed with different types of cancers. Recent data suggest that microRNAs play an important role in the pathogenesis of EC. The aim of the study was to evaluate the involvement of matrix metaloprotease 14 (MMP-14) and microRNA-410 in formation of the EC tumor. To this end expression of MMP-14 and microRNA-410 was assessed within the cancer, transient and healthy zones in the histological sections of tumours using immunohistochemical staining and laser capture microdissection (LCM) followed by a quantitative real-time PCR. The results revealed significantly higher expression of MMP-14 in the cancer tissue zone in comparison to the healthy tissue zone, as well as a lower expression of microRNA-410 in the cancer zone compared with the healthy zone. This reverse correlation may suggest a regulatory role of miRNA-410 in modulating levels of MMP-14 in EC. This is the first report on such regulation in human endometrial cancer. PMID- 26842621 TI - GIPS: A Software Guide to Sequencing-Based Direct Gene Cloning in Forward Genetics Studies. AB - The Gene Identification via Phenotype Sequencing (GIPS) software considers a range of experimental and analysis choices in sequencing-based forward genetics studies within an integrated probabilistic framework, which enables direct gene cloning from the sequencing of several unrelated mutants of the same phenotype without the need to create segregation populations. GIPS estimates four measurements to help optimize an analysis procedure as follows: (1) the chance of reporting the true phenotype-associated gene; (2) the expected number of random genes that may be reported; (3) the significance of each candidate gene's association with the phenotype; and (4) the significance of violating the Mendelian assumption if no gene is reported or if all candidate genes have failed validation. The usage of GIPS is illustrated with the identification of a rice (Oryza sativa) gene that epistatically suppresses the phenotype of the phosphate2 mutant from sequencing three unrelated ethyl methanesulfonate mutants. GIPS is available at https://github.com/synergy-zju/gips/wiki with the user manual and an analysis example. PMID- 26842617 TI - Seasonal influenza vaccine policy, use and effectiveness in the tropics and subtropics - a systematic literature review. AB - AIM: The evidence needed for tropical countries to take informed decisions on influenza vaccination is scarce. This article reviews policy, availability, use and effectiveness of seasonal influenza vaccine in tropical and subtropical countries. METHOD: Global health databases were searched in three thematic areas policy, availability and protective benefits in the context of human seasonal influenza vaccine in the tropics and subtropics. We excluded studies on monovalent pandemic influenza vaccine, vaccine safety, immunogenicity and uptake, and disease burden. RESULTS: Seventy-four countries in the tropics and subtropics representing 60% of the world's population did not have a national vaccination policy against seasonal influenza. Thirty-eight countries used the Northern Hemisphere and 21 countries the Southern Hemisphere formulation. Forty-six countries targeted children and 57 targeted the elderly; though, the age cut-offs varied. Influenza vaccine supply increased twofold in recent years. However, coverage remained lower than five per 1000 population. Vaccine protection against laboratory-confirmed influenza in the tropics ranged from 0% to 42% in the elderly, 20-77% in children and 50-59% in healthy adults. Vaccinating pregnant women against seasonal influenza prevented laboratory-confirmed influenza in both mothers (50%) and their infants <6 months (49-63%). CONCLUSION: Guidelines on vaccine composition, priority risk groups and vaccine availability varied widely. The evidence on vaccine protection was scarce. Countries in the tropics and subtropics need to strengthen and expand their evidence-base required for making informed decisions on influenza vaccine introduction and expansion, and how much benefit to expect. PMID- 26842623 TI - Coronary artery disease and abdominal aortic aneurysm growth. AB - To determine whether coronary artery disease (CAD) is associated with abdominal aortic aneurysm (AAA) growth, we performed a meta-analysis of currently available studies. Databases including MEDLINE and EMBASE were searched through October 2015 using PubMed and OVID. Search terms included enlargement, expansion, growth, or progression; rate or rates; and abdominal aortic aneurysm Studies considered for inclusion met the following criteria: the design was unrestricted; the study population was AAA patients with and without CAD; and outcomes included data regarding AAA growth. For each study, growth rates in both the CAD and non-CAD groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Of 664 potentially relevant publications screened initially, we identified 20 eligible studies including data on a total of 7238 AAA patients. A pooled analysis of all 20 studies demonstrated a statistically significant association of CAD with slower AAA growth rates (i.e. a significantly negative association of CAD with AAA growth) in the fixed-effect model (SMD, 0.06 [-0.0592]; 95% CI, -0.12 [-0.1157] to -0.00 [-0.0027]; p = 0.04). There was minimal between-study heterogeneity (p = 0.16) and a statistically non significant association of CAD with slower AAA growth rates (i.e. a non significantly negative association of CAD with AAA growth) in the pooled result from random-effects modeling (SMD, -0.06; 95% CI, -0.13 to 0.01; p = 0.12). In conclusion, CAD may be negatively associated with AAA growth. PMID- 26842622 TI - Spore Density Determines Infection Strategy by the Plant Pathogenic Fungus Plectosphaerella cucumerina. AB - Necrotrophic and biotrophic pathogens are resisted by different plant defenses. While necrotrophic pathogens are sensitive to jasmonic acid (JA)-dependent resistance, biotrophic pathogens are resisted by salicylic acid (SA)- and reactive oxygen species (ROS)-dependent resistance. Although many pathogens switch from biotrophy to necrotrophy during infection, little is known about the signals triggering this transition. This study is based on the observation that the early colonization pattern and symptom development by the ascomycete pathogen Plectosphaerella cucumerina (P. cucumerina) vary between inoculation methods. Using the Arabidopsis (Arabidopsis thaliana) defense response as a proxy for infection strategy, we examined whether P. cucumerina alternates between hemibiotrophic and necrotrophic lifestyles, depending on initial spore density and distribution on the leaf surface. Untargeted metabolome analysis revealed profound differences in metabolic defense signatures upon different inoculation methods. Quantification of JA and SA, marker gene expression, and cell death confirmed that infection from high spore densities activates JA-dependent defenses with excessive cell death, while infection from low spore densities induces SA-dependent defenses with lower levels of cell death. Phenotyping of Arabidopsis mutants in JA, SA, and ROS signaling confirmed that P. cucumerina is differentially resisted by JA- and SA/ROS-dependent defenses, depending on initial spore density and distribution on the leaf. Furthermore, in situ staining for early callose deposition at the infection sites revealed that necrotrophy by P. cucumerina is associated with elevated host defense. We conclude that P. cucumerina adapts to early-acting plant defenses by switching from a hemibiotrophic to a necrotrophic infection program, thereby gaining an advantage of immunity-related cell death in the host. PMID- 26842625 TI - Podocyturia is significantly elevated in untreated vs treated Fabry adult patients. AB - BACKGROUND: Proteinuria suggests kidney involvement in Fabry disease. We assessed podocyturia, an early biomarker, in controls and patients with and without enzyme therapy, correlating podocyturia with proteinuria and renal function. METHODS: Cross-sectional study (n = 67): controls (Group 1, n = 30) vs. Fabry disease (Group 2, n = 37) subdivided into untreated (2A, n = 19) and treated (2B, n = 18). Variables evaluated: age, gender, creatinine, CKD-EPI, proteinuria, podocyte count/10 20* microscopy power fields, podocytes/100 ml urine, podocytes/g creatininuria (results expressed as median and range). RESULTS: Group 1 vs. 2 did not differ concerning age, gender and CKD-EPI, but differed regarding proteinuria and podocyturia. Group 2A vs. 2B: age: 29 (18-74) vs. 43 (18-65) years (p = ns); gender: males n = 3 (16 %) vs. n = 9 (50 %). Proteinuria was significantly higher in Fabry treated patients, while CKD-EPI and podocyturia were significantly elevated in untreated individuals. Significant correlations: group 2A: age proteinuria, rho = 0.62 (p = 0.0044); age-CKD-EPI, rho = -0.84 (p < 0.0001); podocyturia-podocytes/100 ml urine, rho = 0.99 (p = 0.0001); podocyturia podocytes/g creatininuria rho = 0.86 (p = 0.0003), podocytes/100 ml urine podocytes/g urinary creatinine, rho = 0.84 (p = 0.0004); proteinuria-CKD-EPI, rho = -0.68 (p = 0.0013). Group 2B: podocyturia-podocytes/100 ml urine, rho = 0.88 (p < 0.0001); podocyturia-podocytes/g creatininuria, rho = 0.84 (p < 0.0001); podocytes/100 ml urine-podocytes/g creatininuria, rho = 0.94 (p < 0.0001); CKD EPI-proteinuria, rho = -0.66 (p = 0.0028). CONCLUSIONS: Patients with Fabry disease display heavy podocyturia; those untreated present significantly higher podocyturia, lower proteinuria and better renal function than those who are treated, suggesting that therapy may be started at advanced stages. Podocyturia may antedate proteinuria, and enzyme therapy may protect against podocyte loss. PMID- 26842624 TI - IgM nephropathy: is it closer to minimal change disease or to focal segmental glomerulosclerosis? AB - Immunoglobulin (Ig)M nephropathy (IgMN), known since 1978, is a very controversial clinicopathological entity characterized by IgM diffuse deposits in the mesangium at immunofluorescence whereas light microscop identifies minimal glomerular lesion, hypercellularity and expansion of the mesangium or sclerotic focal, segmental lesion. Clinically, it is a nephrotic syndrome, especially in pediatric patients, or asymptomatic proteinuria and/or isolated hematuria. These characteristics narrowly define IgMN between minimal change disease and focal segmental glomerulosclerosis, so it is not often recognized as a separate pathology. Homogeneous epidemiologic, pathogenetic, clinical or histological data are not available. Recent research on the pathogenetic role of mesangial IgM has, however, renewed interest in IgMN and naturally the controversies. PMID- 26842626 TI - Impact of Detergent-Based Decellularization Methods on Porcine Tissues for Heart Valve Engineering. AB - To date an optimal decellularization protocol of heart valve leaflets (HVL) and pericardia (PER) with an adequate preservation of the extracellular matrix (ECM) is still lacking. This study compares a 4 day Triton X-100-based protocol with faster SDC-based protocols for the decellularization of cardiac tissues. Decellularized and non-treated HVL and PER were processed for histological, biochemical and mechanical analysis to determine the effect of these agents on the structure, ECM components, and biomechanical properties. Tissues treated with SDC-based protocols still showed nuclear material, whereas tissues treated with Triton X-100 1% + ENZ +/- TRYP were completely cell free. For both decellularized tissues, an almost complete washout of glycosaminoglycans, a reduction of soluble collagen and an alteration of the surface ultrastructure was observed. Interestingly, only the elastic fibers of pericardial tissue were affected and this tissue had a decreased maximum load. This study showed that both detergents had a similar impact on the ECM. However, Triton X-100 1% +DNase/RNase (ENZ) +/- Trypsin (TRYP) is the only protocol that generated completely cell free bioscaffolds. Also, our study clearly demonstrated that the decellularization agents have more impact on pericardial tissues than on heart valve leaflets. Thus, for the purpose of tissue engineering of heart valves, it is advisable to use valvular rather than pericardial matrices. PMID- 26842627 TI - Differential effect of lithium on cell number in the hippocampus and prefrontal cortex in adult mice: a stereological study. AB - OBJECTIVES: Neuroimaging studies have revealed lithium-related increases in the volume of gray matter in the prefrontal cortex (PFC) and hippocampus. Postmortem human studies have reported alterations in neuronal and glial cell density and size in the PFC of lithium-treated subjects. Rodents treated with lithium exhibit cell proliferation in the dentate gyrus (DG) of the hippocampus. However, it is not known whether hippocampal and PFC volume are also increased in these animals or whether cell number in the PFC is altered. METHODS: Using stereological methods, this study estimated the total numbers of neurons and glia, and the packing density of astrocytes in the DG and PFC of normal adult mice treated with lithium, and evaluated the total volume of these regions and the entire neocortex. RESULTS: Lithium treatment increased the total numbers of neurons and glia in the DG (by 25% and 21%, respectively) and the density of astrocytes but did not alter total numbers in the PFC. However, the volumes of the hippocampus and its subfields, the PFC and its subareas, and the entire neocortex were not altered by lithium. CONCLUSIONS: Both neuronal and glial cells accounted for lithium-induced cell proliferation in the DG. That the numbers of neurons and glia were unchanged in the PFC is consistent with the view that this region is not a neurogenic zone. Further studies are required to clarify the impact of lithium treatment on the PFC under pathological conditions and to investigate the dissociation between increased cell proliferation and unchanged volume in the hippocampus. PMID- 26842629 TI - An experimental study of the intrinsic stability of random forest variable importance measures. AB - BACKGROUND: The stability of Variable Importance Measures (VIMs) based on random forest has recently received increased attention. Despite the extensive attention on traditional stability of data perturbations or parameter variations, few studies include influences coming from the intrinsic randomness in generating VIMs, i.e. bagging, randomization and permutation. To address these influences, in this paper we introduce a new concept of intrinsic stability of VIMs, which is defined as the self-consistence among feature rankings in repeated runs of VIMs without data perturbations and parameter variations. Two widely used VIMs, i.e., Mean Decrease Accuracy (MDA) and Mean Decrease Gini (MDG) are comprehensively investigated. The motivation of this study is two-fold. First, we empirically verify the prevalence of intrinsic stability of VIMs over many real-world datasets to highlight that the instability of VIMs does not originate exclusively from data perturbations or parameter variations, but also stems from the intrinsic randomness of VIMs. Second, through Spearman and Pearson tests we comprehensively investigate how different factors influence the intrinsic stability. RESULTS: The experiments are carried out on 19 benchmark datasets with diverse characteristics, including 10 high-dimensional and small-sample gene expression datasets. Experimental results demonstrate the prevalence of intrinsic stability of VIMs. Spearman and Pearson tests on the correlations between intrinsic stability and different factors show that #feature (number of features) and #sample (size of sample) have a coupling effect on the intrinsic stability. The synthetic indictor, #feature/#sample, shows both negative monotonic correlation and negative linear correlation with the intrinsic stability, while OOB accuracy has monotonic correlations with intrinsic stability. This indicates that high-dimensional, small-sample and high complexity datasets may suffer more from intrinsic instability of VIMs. Furthermore, with respect to parameter settings of random forest, a large number of trees is preferred. No significant correlations can be seen between intrinsic stability and other factors. Finally, the magnitude of intrinsic stability is always smaller than that of traditional stability. CONCLUSION: First, the prevalence of intrinsic stability of VIMs demonstrates that the instability of VIMs not only comes from data perturbations or parameter variations, but also stems from the intrinsic randomness of VIMs. This finding gives a better understanding of VIM stability, and may help reduce the instability of VIMs. Second, by investigating the potential factors of intrinsic stability, users would be more aware of the risks and hence more careful when using VIMs, especially on high-dimensional, small-sample and high complexity datasets. PMID- 26842631 TI - Call for papers - special issue on Challenges to women's sexual and reproductive health. PMID- 26842630 TI - A porous metal-organic framework with a unique hendecahedron-shaped cage: structure and controlled drug release. AB - A porous MOF constructed from a [Cu2(COO)4] secondary building unit, H3L (H3L = [1,1';3',1'']terphenyl-4,5',4''-tricarboxylic acid), and pyrazine ligands features a unique hendecahedron cage-like cavity with good stability and a high BET surface area of 3235 m(2) g(-1), showing good controlled drug release property of ibuprofen over those of anethole and guaiacol. PMID- 26842628 TI - IgE-tailpiece associates with alpha-1-antitrypsin (A1AT) to protect IgE from proteolysis without compromising its ability to interact with FcepsilonRI. AB - Several splice variants of IgE exist in human plasma, including a variant called IgE-tailpiece (IgE-tp) that differs from classical IgE by the replacement of two carboxy-terminal amino acids with eight novel residues that include an ultimate cysteine. To date, the role of the secreted IgE-tp isoform in human immunity is unknown. We show that levels of IgE-tp are raised in helminth-infected donors, and that both the classical form of IgE (IgE-c) and IgE-tp interact with polymers of the serine protease inhibitor alpha-1-antitrypsin (A1AT). The association of IgE-tp with A1AT polymers in plasma protects the antibody from serine protease mediated degradation, without affecting the functional interaction of IgE-tp with important receptors, including FcepsilonR1. That polymers of A1AT protect IgE from degradation by helminth proteases may explain why these common and normally non-disease causing polymorphic variants of A1AT have been retained by natural selection. The observation that IgE can be complexed with polymeric forms of A1AT may therefore have important consequences for our understanding of the pathophysiology of pulmonary diseases that arise either as a consequence of A1AT deficiency or through IgE-mediated type 1 hypersensitivity responses. PMID- 26842632 TI - Lifestyle habits and women's attitudes towards discussing them at a visit for contraceptive advice. AB - OBJECTIVE: The aims of this study was to use visits for contraceptive counselling as opportunities for examining women's actual life style habits with the main focus being placed on alcohol consumption but also to evaluate the women's opinions about discussing their alcohol and tobacco habits and their weight status. METHODS: A total of 535/802 (67%) women completed a study-specific anonymous questionnaire after a contraceptive counselling visit with a midwife. RESULTS: A majority of the women thought that a discussion concerning alcohol habits at a contraceptive counselling session was important (85.5%) and not intrusive (86.4%) neither embarrassing (81.7%). Women with high-risk drinking habits were younger, more often tobacco users and more often planning for childbirth in the future, compared with women who did not display high-risk drinking behaviour. A significantly higher percentage of women who practiced high risk drinking thought that a discussion of alcohol was intrusive (10.9%) and embarrassing (46.7%), compared with women not practicing high-risk alcohol consumption. Most women (72.9%) stated that no other caregiver during the preceding year except the midwife had discussed drinking habits with them. The weight was a good thing that the midwife brought up for discussion according to 82.5% of the women but the discussions about weight was more often found embarrassing (18.4%) than the discussion about alcohol habits. CONCLUSION: Women who came for contraceptive counselling found the discussion concerning alcohol habits important, not intrusive or embarrassing and a good thing to be brought up by the midwife. PMID- 26842633 TI - Prevalence, reasons and predictors for home births among pregnant women attending antenatal care in Birnin Kudu, North-west Nigeria. AB - OBJECTIVE: To determine the prevalence, reasons and predictors for home birth in a rural community. METHOD: Descriptive cross sectional study which utilised a pretested interviewer administered semi-structured questionnaire to assess the place of delivery in their last childbirth among 410 pregnant women attending antenatal care in Birnin Kudu, Nigeria. Logistic regression analysis was used to assess the relative effect of determinants. RESULT: PREVALENCE: Of the 410 women, 248 (60.5%) delivered at home in their last childbirth. Self reported reasons: Home birth was opted for because of: lack of transportation 113 (45.6%), onset of labour was at night 104 (41.9 %), preferred birthing position 72 (29.0%), tradition 60 (24.2%), fear of surgery 42 (16.9%) and poor attitude of health workers 32 (12.9%). PREDICTORS: The odds of giving birth at home was 3.88 times higher in women with informal education (adjusted OR 3.88; 95% CI: 2.51, 6.00) and the odds of giving birth at home was 0.27 for women with less than 5 deliveries compared with women with 5 or more deliveries (adjusted OR 0.27; 95% CI: 0.15, 0.49) after controlling for confounders. CONCLUSION: The prevalence of home birth is high in Birnin Kudu and according to our respondents the main reasons for this practice are onset of labour late at night with lack of transportation and a limited choice of birthing positions. Provision of training and retraining of skilled birth attendants to assist women birthing in squatting positions would encourage women to deliver in the hospitals. PMID- 26842634 TI - Being a homebirth midwife in the Nordic countries - a phenomenological study. AB - OBJECTIVE: To describe the lived experience of being a homebirth midwife in the Nordic countries. METHODS: Interviews conducted with 21 homebirth midwives from the five Nordic countries were analyzed with a phenomenological approach. RESULTS: The essential structure of being a homebirth midwife in the Nordic countries can be understood as realizing altruistic values and fulfilling one's own desires for working life, by facilitating the desires of the women giving birth. By being "active-passive" - using all her senses and letting her intuition lead her - the midwife supports women during labor and birth. Medical skills, evidence-based knowledge and experience are important for providing the optimal care in each situation. Further this becomes the midwife's chosen lifestyle, which alters her own self, making her available to assist the mother-to-be in fulfilling her wishes for a good birth. Finally, being able to use one's own full potential during a home birth is experienced as the ideal way of working as a midwife, practicing the art of midwifery. CONCLUSION: The experience of being a homebirth midwife in the Nordic countries includes making an adaption to a lifestyle that is considered the basis for a satisfactory and rewarding way of working. A sense of fulfillment is achieved through experiencing the possibility to work according to one's own ideals concerning the art of midwifery. The beliefs about a woman's ability to give birth and understanding the importance of a positive birth for both the mother and the newborn baby are essential. PMID- 26842635 TI - The characteristics of women who birth at home, in a birth centre or in a hospital labour ward: A study of a nationally-representative sample of 1835 pregnant women. AB - OBJECTIVES: A woman's choice of birth setting can depend on a variety of factors including her preference, availability of services and legislative environment. However, examination of the characteristics of women in relation to their birth environment has been limited in scope and design. This study presents the comparative characteristics of women who birth at home, in a birth centre or in a standard hospital setting. METHODS: Cross-sectional survey of women (n = 2445) identified as pregnant or recently given birth in the 2009 survey of the "young" cohort (n = 8012) from the Australian Longitudinal Study on Women's Health. RESULTS: Women's birth setting was associated with a variety of factors including employment status, private health insurance, attitudes towards obstetric care, health status, use of intrapartum pain management, and adverse birth events. CONCLUSION: Women's choice of birth setting may be affected by factors such as government and institutional policy, personal values, and economic situation. The confluence of these factors for individual women can impact on the birth settings available to women and the corresponding choices they make. A clear understanding of these factors is important to ensure women access the most appropriate birth environment to achieve the best maternal and foetal health outcomes. PMID- 26842636 TI - Home birth constructed as a safe choice in Iceland: A content analysis on Icelandic media. AB - BACKGROUND: The rate of home birth in Iceland increased from 0.1% in the 90's, to 2.2% in 2012. As the media contributes to the development and public perceptions, engagement and use of health care, it is of interest to explore the media representation of planned home birth in Iceland. OBJECTIVES: The aim of this study was to explore the way in which the constructions of planned home birth are represented in the Icelandic media; the frequency with which planned home birth was discussed and by whom it was discussed; whether the discourse was congruent with practice development in the country; and if so, how such congruency was effected. METHODS: Data from the main newspapers in Iceland published from the beginning of 1990 until the end of 2011 were explored using content analysis. RESULTS: In total, 127 items were summarized and we identified five themes: approach to safety, having a choice, the medicalization of childbirth, the relationship between women and midwives, and the reaction of the pregnant woman's local community. Central in the analysis were the importance of being able to choose a safe place of birth and the need for woman-centred care. CONCLUSION: Overall planned home birth was not discussed with much intensity or frequency, but in general the discussion was shaped by a positive attitude. There was a distinction in the public media discourse among midwives and physicians or obstetricians who do not argue against planned home birth but who nevertheless speak with caution. The pregnant women who chose home birth found their own home to be safe and similar views were identified among women and midwives. PMID- 26842637 TI - Primiparous women's preferences for care during a prolonged latent phase of labour. AB - OBJECTIVE: To investigate primiparous women's preferences for care during a prolonged latent phase of labour. METHODS: A qualitative study based on focus groups and individual interviews and analysed with inductive content analysis. RESULTS: Sixteen primiparous women with a prolonged latent phase of labour >18 hours were interviewed in five focus groups (n = 11) or individually (n = 5). One main category emerged "Beyond normality - a need of individual adapted guidance in order to understand and manage an extended latent phase of labour" which covers the women's preferences during the prolonged latent phase. Five categories were generated from the data: "A welcoming manner and not being rejected", "Individually adapted care", "Important information which prepares for reality and coping", "Participation and need for feedback" and "Staying nearby the labour ward or being admitted for midwifery support". Women with a prolonged latent phase of labour sought to use their own resources, but their needs for professional support increased as time passed. A welcoming attitude from an available midwife during the latent phase created a feeling of security, and personally adapted care was perceived positively. CONCLUSIONS: Women with a prolonged latent phase of labour preferred woman-centred care. Midwives play an important role in supporting these women. Women's need for midwifery-support increases as the time spent in latent phase increases. PMID- 26842638 TI - Risk factors for anal sphincter tears in vacuum-assisted delivery. AB - OBJECTIVE: The aim of the present study was to describe the prevalence of anal sphincter tears (AST) in relation to obstetric management and technique during vacuum extraction deliveries (VE) (re: indications, the station of the fetal head at application of the cup, number of tractions, the length for the extraction, cup detachments, pain relief, episiotomy, fetal presentation, and experience of the operator) as well as maternal and infant anthropometrics. METHODS: Descriptive study. Data on six hundred vacuum extraction deliveries were consecutively collected from six different delivery units in Sweden. Each unit contributed with data on 100 deliveries. The final study population included 596 women who delivered by vacuum extraction. RESULTS: There was no correlation between the management of the vacuum extraction and risk for anal sphincter tear. Women from Africa had nearly a fourfold risk for anal sphincter tear during vacuum-assisted delivery compared with Swedish-born women (OR 3.82 CI 1.47-9.89). Compared with infants with birth weight less than 4000 g, birth weight above 4000 g was associated with increased risk of AST (OR 1.87 CI 1.06-3.28). CONCLUSIONS: In this study, the obstetric management in VE-assisted deliveries did not impact the risk of AST. PMID- 26842639 TI - "Nature makes you blind to the risks": An exploration of womens' views surrounding decisions on the timing of childbearing in contemporary society. AB - OBJECTIVE: To gain an understanding of womens' views surrounding decisions on the timing of childbearing. STUDY DESIGN: This study was based on interviews with 18 childless women, from North-West England, in three age groups: Six women aged between 18 and 24; Six women aged between 25 and 34; and six women aged 35 or more. Data were analysed using a hermeneutic phenomenological approach with thematic analysis. RESULTS: Three main themes were identified. Women perceived themselves as living within boundaries, defined internally and externally; they aspired to being a great mother or no mother; and had a desire to contribute to family and society, at multiple levels. Risks associated with delaying childbearing had little or no influence on decision-making. The overarching phenomenon was social comparability; decisions were made in the context of women's knowledge and perceptions of others and a high degree of critical self evaluation. CONCLUSION: We conclude that social reality dominates womens' reproductive decisions. Whilst the biological reality is that fertility reduces and medical complications increase with maternal age, social discourses deter women from acknowledging this. Medical risks associated with advanced maternal age are undermined by the notion that women can choose when to start a family. PMID- 26842640 TI - Fathers' experiences of a vacuum extraction delivery - a qualitative study. AB - OBJECTIVE: To explore fathers' experiences of a birth by vacuum extraction (VE). METHOD: A qualitative interview study with 10 fathers analysed with qualitative content analysis. FINDINGS: The theme 'affected but helpless' refers to the father's role changing when childbirth terminates with a VE. From initially being involved in the delivery, his role switches to being merely an observer at the mercy of the professionals' knowledge and guidance. The VE procedure evoked concerns over the mother's and the child's safety and wellbeing, even if the fathers wanted the birth process to be over. The fathers considered the choice of conducting a VE as an adequate alternative, but they expressed concerns about consequences on future decisions. The theme encompasses all the main categories: wish to be involved, anxious observer, turbulent feelings and thoughts about consequences. CONCLUSIONS: VE delivery has a strong emotional impact on fathers and the procedure is often experienced as a dramatic way to end a birth and an ultimate way to terminate a long birth process. The results indicate that a lack of support and of a genuine opportunity to participate, as well as the mother's pain impair their experience, not the VE delivery, per se. PMID- 26842641 TI - Neither father nor biological mother. A qualitative study about lesbian co mothers' maternity care experiences. AB - OBJECTIVE: To explore lesbian co-mothers' maternity care experiences and their implications for the caring encounter. METHODS: A qualitative interview study with data from a convenience sample of eleven Norwegian comothers was conducted. Systematic text condensation was used for data analysis. RESULTS: Analysis showed that ordinary tokens of recognition created feelings of being included, while lesbian self-confidence played a major role in awkward encounters. Being neither father nor biological mother sometimes challenged parental identity. Being women helped co-mothers understand what their partners went through but they had to find other ways of mothering than if they had given birth themselves. Co-mothers addressed themselves with different terms and perceived some concepts as unnatural or excluding. Parental identity was defined by their relationship to baby, and the term "co-mother" was perceived as a bureaucratic concept. CONCLUSION: For lesbian co-mothers, being recognized in maternity care implies that they are valued for the qualities that separate them from other user groups on a personal level. On a societal level, being recognized is related to acknowledgement of inventive ways of doing family. Everyday signs of recognition may prevent moral violation, and by paying particular attention to use of language, staff can help co-mothers feel acknowledged. PMID- 26842642 TI - Swedish midwives' perception of their practice environment - A cross sectional study. AB - BACKGROUND: There is a shortage of midwives in Sweden. Evidence suggests that the work environment is likely to play a part in retention and attrition rates. OBJECTIVE: To explore the practice environment of Swedish midwives and factors associated with the perception of an unfavorable work environment. METHODS: 475/1000 (48.6%) members of the Swedish Midwifery association completed a questionnaire including the Practice Environment Scale (PES). Differences in mean scores were calculated for the subscales of PES and midwives' background characteristics. Logistic regression was used to investigate factors most strongly associated with unfavorable working environment. RESULTS: The two domains that showed significant differences in terms of participant characteristics were the Staffing and resources adequacy subscale and the Foundations of quality care subscale. Midwives younger than 40 years, those with less than 10 years' experience and those with an additional academic degree rated these two domains more unfavorably. Protective factors for assessing the work environment unfavorable were mainly internal such as high quality of life and high self-efficacy. Swedish midwives were most satisfied with the midwife-doctor relationship and least satisfied with their participation in work place or hospital affairs. Midwives suffering from burnout, those who provided hospital based care and those without leadership position were more likely to assess their work environment as unfavorable. CONCLUSIONS: This study identified personal factors as well as work related factors to be associated with midwives' assessment of their practice work environment. Establishing healthy work places where midwives feel recognized and valued could prevent midwives from leaving the profession. PMID- 26842643 TI - Birth preferences by nulliparous women and their partners in Turkey. AB - OBJECTIVE: The aim of this study was to examine the preferences of nulliparous women and their partners in giving birth and the reasons for these preferences. METHODS: The sample in this cross-sectional study consisted of 162 pregnant women in the last trimester of pregnancy and their partners. Data collection was accomplished using a questionnaire. RESULTS: It was found that most women (90.8%) and their partners (92%) preferred a vaginal birth. The couples' birth preferences were generally similar to one another. The main reasons for the choice of a vaginal birth were that it was natural and healthier for the mother and child and that recovery and discharge from the hospital were quicker. The main reasons for the choice of cesarean section were fear of childbirth and not putting the baby at risk. CONCLUSIONS: Antenatal education may help to reduce the number of elective cesarean sections by changing the negative perceptions of vaginal birth and reducing the fear of childbirth. PMID- 26842644 TI - Norwegian midwives' use of screening for and brief interventions on alcohol use in pregnancy. AB - OBJECTIVE: This study assessed the current screening for and brief intervention (BI) on alcohol use in pregnancy among midwives in Norway, as well as perceived barriers for such practice. DESIGN, SETTING AND PARTICIPANTS: An Internet and telephone survey was conducted among all 200 registered municipal midwives in the Norwegian health regions North, West and South in the period December 2013-May 2014. Of these, 103 midwives were reached and responded (52%). MEASUREMENT AND FINDINGS: Most of the midwives (97%) asked the pregnant women about their alcohol use at their first consultation. 42% of the midwives reported using a screening instrument. When asked which one, AUDIT or TWEAK was mentioned by 16%. The need for more training in screening tools was reported by 66%. Sixty-four percent of midwives working in municipalities that had received special training compared with 50% among the rest said that they intervened themselves if alcohol use was detected (chi(2) = 0.32, P = .645). Motivational Interviewing was well known and frequently used. Low perceived BI competence and finding it difficult to discuss alcohol use with parents with a different ethnicity both reduced chances of carrying out a BI. Time constraints and lack of organizational support were other frequently mentioned barriers. KEY CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: It seems that the Norwegian midwives find screening and brief interventions for alcohol use to be important and part of their job, but still could use more training, stronger guidelines and more time for following up parents. PMID- 26842645 TI - Maternal emotional wellbeing over time and attachment to the fetus when a malformation is detected. AB - OBJECTIVES: To explore women's emotional wellbeing and attachment to the fetus when informed during pregnancy of a fetal malformation. METHODS: In a longitudinal community-based study, 56 pregnant women with a detected fetal malformation and continued pregnancy were invited to complete questionnaires in mid-pregnancy, two months postpartum and one year postpartum. The questionnaire included the Edinburgh Postnatal Depression Scale, the Cambridge Worry Scale, the State-Trait Anxiety Inventory, and the Maternal-Fetal Attachment Scale. Socio demographics and obstetric background data were also collected. Descriptive statistical analyses were performed. RESULTS: Approximately 84% returned the questionnaires and 37% of women in mid-pregnancy, 26.5% two months postpartum and 22% one year postpartum were found to have depressive symptoms. In mid-pregnancy 8.9% had thoughts of harming themselves, and almost all reported at least one major worry. Worry about the relationship with their husband or partner increased two months postpartum and one year postpartum. The means of both state and trait anxiety levels were high on all three measuring occasions and the mean score for maternal-fetal attachment was 3.7 (SD 0.67), indicating a high level of attachment. CONCLUSION: The results highlight the importance of adequate support when fetal malformations are detected on ultrasound examination. PMID- 26842646 TI - Lost in the crowd? Using eye-tracking to investigate the effect of complexity on attribute non-attendance in discrete choice experiments. AB - BACKGROUND: The provision of additional information is often assumed to improve consumption decisions, allowing consumers to more accurately weigh the costs and benefits of alternatives. However, increasing the complexity of decision problems may prompt changes in information processing. This is particularly relevant for experimental methods such as discrete choice experiments (DCEs) where the researcher can manipulate the complexity of the decision problem. The primary aims of this study are (i) to test whether consumers actually process additional information in an already complex decision problem, and (ii) consider the implications of any such 'complexity-driven' changes in information processing for design and analysis of DCEs. METHODS: A discrete choice experiment (DCE) is used to simulate a complex decision problem; here, the choice between complementary and conventional medicine for different health conditions. Eye tracking technology is used to capture the number of times and the duration that a participant looks at any part of a computer screen during completion of DCE choice sets. From this we can analyse what has become known in the DCE literature as 'attribute non-attendance' (ANA). Using data from 32 participants, we model the likelihood of ANA as a function of choice set complexity and respondent characteristics using fixed and random effects models to account for repeated choice set completion. We also model whether participants are consistent with regard to which characteristics (attributes) they consider across choice sets. RESULTS: We find that complexity is the strongest predictor of ANA when other possible influences, such as time pressure, ordering effects, survey specific effects and socio-demographic variables (including proxies for prior experience with the decision problem) are considered. We also find that most participants do not apply a consistent information processing strategy across choice sets. CONCLUSIONS: Eye-tracking technology shows promise as a way of obtaining additional information from consumer research, improving DCE design, and informing the design of policy measures. With regards to DCE design, results from the present study suggest that eye-tracking data can identify the point at which adding complexity (and realism) to DCE choice scenarios becomes self-defeating due to unacceptable increases in ANA. Eye-tracking data therefore has clear application in the construction of guidelines for DCE design and during piloting of DCE choice scenarios. With regards to design of policy measures such as labelling requirements for CAM and conventional medicines, the provision of additional information has the potential to make difficult decisions even harder and may not have the desired effect on decision-making. PMID- 26842650 TI - Vaccinating against HPV: A Call to Action. PMID- 26842649 TI - FDA Approves Eribulin for Advanced Liposarcoma. PMID- 26842647 TI - A Nuclear Attack on Traumatic Brain Injury: Sequestration of Cell Death in the Nucleus. AB - BACKGROUND: Exportin 1 (XPO1/CRM1) plays prominent roles in the regulation of nuclear protein export. Selective inhibitors of nuclear export (SINE) are small orally bioavailable molecules that serve as drug-like inhibitors of XPO1, with potent anti-cancer properties. Traumatic brain injury (TBI) presents with a secondary cell death characterized by neuroinflammation that is putatively regulated by nuclear receptors. AIMS AND RESULTS: Here, we report that the SINE compounds (KPT-350 or KPT-335) sequestered TBI-induced neuroinflammation-related proteins (NF-(k)B, AKT, FOXP1) within the nucleus of cultured primary rat cortical neurons, which coincided with protection against TNF-alpha (20 ng/mL) induced neurotoxicity as shown by at least 50% and 100% increments in preservation of cell viability and cellular enzymatic activity, respectively, compared to non-treated neuronal cells (P's < 0.05). In parallel, using an in vivo controlled cortical impact (CCI) model of TBI, we demonstrate that adult Sprague-Dawley rats treated post-injury with SINE compounds exhibited significant reductions in TBI-induced behavioral and histological deficits. Animals that received KPT-350 orally starting at 2 h post-TBI and once a day thereafter over the next 4 days exhibited significantly better motor coordination, and balance in the rotorod test and motor asymmetry test by 100-200% improvements, as early as 4 h after initial SINE compound injection that was sustained during subsequent KPT 350 dosing, and throughout the 18-day post-TBI study period compared to vehicle treatment (P's < 0.05). Moreover, KPT-350 reduced cortical core impact area and peri-impact cell death compared to vehicle treatment (P's < 0.05). CONCLUSIONS: Both in vitro and in vivo experiments revealed that KPT-350 increased XPO1, AKT, and FOXP1 nuclear expression and relegated NF-(k)B expression within the neuronal nuclei. Altogether, these findings advance the utility of SINE compounds to stop trafficking of cell death proteins within the nucleus as an efficacious treatment for TBI. PMID- 26842648 TI - Pharmacological evidence that potentiation of plasmalemmal Ca(2+)-extrusion is functionally coupled to inhibition of SR Ca(2+)-ATPases in vascular smooth muscle cells. AB - Cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic reticulum (SR) Ca(2+)-ATPases, causes slowly developing and subsequently diminishing characteristic contractions in vascular smooth muscle, and the second application of CPA has incompletely repeatable effects, depending on the vessel type. The objective of the present study was to examine the mechanisms underlying the significant decrease of CPA-induced contractions upon the second application. A pharmacological intervention of Ca(2+) extrusion process as a strategy was performed to modulate vasoconstrictor effects of CPA in rat aortic ring preparations. CPA-induced contractions, expressed as percentages of the contractions induced by KCl (80 mM), were significantly decreased from 44.1 +/- 5.7 to 7.6 +/- 1.8 % (P < 0.001) upon the second application. The contractions, however, were completely repeatable in the presence of vanadate, an inhibitor of ATPases, but not of ouabain, an inhibitor of Na(+)-pumps. Strikingly, CPA-induced contractions were sustained and completely repeatable in Na(+)-free and low Na(+) medium. Furthermore, we found that the contractions were completely repeatable in the presence of 2',4'-dichlorobenzamil, an inhibitor of the forward mode of Na(+)/Ca(2+) exchangers, but not of KBR7943, an inhibitor of the reverse mode of Na(+)/Ca(2+) exchangers. Our findings indicate that CPA by inducing a transient rise in cytosolic Ca(2+) level causes a long-lasting upregulation of plasma membrane (PM) Ca(2+) extruders and thus leads to a diminished contraction upon its second application in blood vessels. This suggests that there is a functional coupling between PM Ca(2+) extruders and SR Ca(2+)-ATPases in rat aortic smooth muscle cells. PMID- 26842651 TI - A novel caveolin-1/p85alpha/Rab5/Tiam1/Rac1 signaling axis in tumor cell migration and invasion. AB - The small GTPase Rab5 has been frequently studied in the context of intracellular trafficking, but evidence obtained more recently has implicated Rab5 as a critical regulator of cell adhesion, migration and invasion in both normal and tumor cells. These recent findings showing that Rab5 promotes Rac1 activation and focal adhesion dynamics have highlighted the question as to what the upstream regulators of Rab5 activity might be and how these are connected to cell migration. The efforts to shed light on this issue identified in metastatic cancer cells a novel Caveolin-1/p85alpha/Rab5/Tiam1/Rac1 signaling axis relevant to cancer cell migration and invasion. In this addendum, we highlight aspects concerning Rab5 regulation in this context. PMID- 26842653 TI - Quantitative carbon detector for enhanced detection of molecules in foods, pharmaceuticals, cosmetics, flavors, and fuels. AB - Analysis of trace compounds, such as pesticides and other contaminants, within consumer products, fuels, and the environment requires quantification of increasingly complex mixtures of difficult-to-quantify compounds. Many compounds of interest are non-volatile and exhibit poor response in current gas chromatography and flame ionization systems. Here we show the reaction of trimethylsilylated chemical analytes to methane using a quantitative carbon detector (QCD; the PolyarcTM reactor) within a gas chromatograph (GC), thereby enabling enhanced detection (up to 10*) of highly functionalized compounds including carbohydrates, acids, drugs, flavorants, and pesticides. Analysis of a complex mixture of compounds shows that the GC-QCD method exhibits faster and more accurate analysis of complex mixtures commonly encountered in everyday products and the environment. PMID- 26842652 TI - Influence of changes in serum uric acid levels on renal function in elderly patients with hypertension: a retrospective cohort study with 3.5-year follow-up. AB - BACKGROUND: Hyperuricemia is closely related to renal diseases. Therefore, the aim of this study was to explore the relationship between the longitudinal changes in serum uric acid and the estimated glomerular filtration rate (eGFR) in a cohort of elderly hypertensive patients. METHODS: Eighty hundred and thirty seven re-hospitalized patients with hypertension were included in this retrospective cohort study. Multiple regression analysis was used to investigate the relationship between changes in serum uric acid and renal function after 3.5 years follow-up. RESULTS: The average age at baseline was 69.0+/-10.0 years, and the average follow-up duration was 3.5 years. Multiple linear regression analysis showed that the baseline uric acid levels had a linearly negative correlation with baseline eGFR (P < 0.01), after adjustment for age, gender, blood pressure, and body mass index, et al. An increase of 100 MUmol/L baseline uric acid level resulted in a decrease of 5.684 ml/min/1.73 m(2) in eGFR [95% confidence interval (CI): 7.735-3.633]. Patients with increased uric acid levels had higher risk of renal function decline over the follow-up period, with an adjusted odds ratio of 1.639 (95% CI: 1.129-2.378, P = 0.009) , whereas eGFR was remained unchanged in patients with hyperuricemia at baseline and with normal uric acid level 3.5-year later. CONCLUSIONS: Longitudinal changes in uric acid levels were independently associated with the renal function decline in elderly patients with hypertension. Uric acid level should be considered in hypertension management in the elderly. PMID- 26842654 TI - Hartung-Knapp method is not always conservative compared with fixed-effect meta analysis. AB - A widely used method in classic random-effects meta-analysis is the DerSimonian Laird method. An alternative meta-analytical approach is the Hartung-Knapp method. This article reports results of an empirical comparison and a simulation study of these two methods and presents corresponding analytical results. For the empirical evaluation, we took 157 meta-analyses with binary outcomes, analysed each one using both methods and performed a comparison of the results based on treatment estimates, standard errors and associated P-values. In several simulation scenarios, we systematically evaluated coverage probabilities and confidence interval lengths. Generally, results are more conservative with the Hartung-Knapp method, giving wider confidence intervals and larger P-values for the overall treatment effect. However, in some meta-analyses with very homogeneous individual treatment results, the Hartung-Knapp method yields narrower confidence intervals and smaller P-values than the classic random effects method, which in this situation, actually reduces to a fixed-effect meta analysis. Therefore, it is recommended to conduct a sensitivity analysis based on the fixed-effect model instead of solely relying on the result of the Hartung Knapp random-effects meta-analysis. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26842656 TI - Immunogenetics of complement in mixed cryoglobulinaemia. AB - OBJECTIVES: A low C4 level is one of the hallmarks of mixed cryoglobulinaemia (MC). However, several reports suggest that other factors may be involved in C4 depletion. The C4 gene is located in a multiallelic CNV locus in the human MHC region. We studied the C4 gene copy number (GCN) and both C4A and C4B isotypes, as well as the presence of the hypofunctional C4A6 allotype (rs41315824) and C4A0 allotype (rs367709216) in 41 MC patients, 16 SLE patients and 78 healthy controls. METHODS: GCN of the C4 gene were evaluated by real time PCR. C4A6 allotype (p.Arg458Trp) and ins 2-bp mutation in exon 29 were screened by primer extension. Correlation with clinical signs of the disease (cutaneous ulcers, peripheral neuropathy, GN, purpura, hepatitis) have been performed by cluster analysis, (K-means algorithm). RESULTS: C4 GCN analysis showed that fewer MC patients had more than 2 copies of the C4A gene as well as a lower C4A gene-copy index (1.90 +/- 0.54 vs. 2.21 +/- 0.78) as compared to healthy controls. SNP rs41315824 analysis showed a significant increase in the frequency of the p.Arg458Trp (C4A6) variant in cryoglobulinaemic patients. Lastly, cluster analysis allowed us to identify two separate clusters of patients. The cluster that included patients with three or less C4 gene copies was found to have a greater prevalence of the most severe complications such as glomerulonephritis, neuropathy and severe cutaneous ulcers. CONCLUSIONS: These data suggest there may be a relationship between polymorphisms of the C4 gene and clinical presentation. PMID- 26842655 TI - Dual-functionalized liposomal delivery system for solid tumors based on RGD and a pH-responsive antimicrobial peptide. AB - [D]-H6L9, as a pH-responsive anti-microbial peptide (AMP), has been evidenced by us to be an excellent choice in tumor microenvironment-responsive delivery as it could render liposomes responsive to the acidified tumor microenvironment. However, [D]-H6L9-modified liposomes could not actively target to tumor area. Therefore, integrin alphavbeta3-targeted peptide RGD was co-modified with [D] H6L9 onto liposomes [(R + D)-Lip] for improved tumor delivery efficiency. Under pH 6.3, (R + D)-Lip could be taken up by C26 cells and C26 tumor spheroids (integrin alphavbeta3-positive) with significantly improved efficiency compared with other groups, which was contributed by both RGD and [D]-H6L9, while RGD did not increase the cellular uptake performance on MCF-7 cells (integrin alphavbeta3 negative). Results showed that RGD could decrease cellular uptake of (R + D)-Lip while [D]-H6L9 could increase it, implying the role of both RGD and [D]-H6L9 in cellular internalization of (R + D)-Lip. On the other hand, (R + D)-Lip could escape the entrapment of lysosomes. PTX-loaded (R + D)-Lip could further increase the cellular toxicity against C26 cells compared with liposomes modified only with RGD and [D]-H6L9 respectively, and achieve remarkable tumor inhibition effect on C26 tumor models. PMID- 26842657 TI - Why mothers still deliver at home: understanding factors associated with home deliveries and cultural practices in rural coastal Kenya, a cross-section study. AB - BACKGROUND: Maternal mortality has declined by 43 % globally between 1990 and 2013, a reduction that was insufficient to achieve the 75 % reduction target by millennium development goal (MDG) five. Kenya recorded a decline of 18 % from 490 deaths in 1990 to 400 deaths per 100,000 live births in 2013. Delivering at home, is associated with higher risk of maternal deaths, therefore reducing number of home deliveries is important to improve maternal health. In this study, we aimed at establishing the proportion of home deliveries and evaluating factors associated with home deliveries in Kilifi County. METHODS: The study was conducted among mothers seeking immunization services in selected health facilities within Kilifi County using Semi-structured questionnaires administered through face to face oral interviews to collect both quantitative and qualitative data. Six Focus Group Discussion (FGD) and ten in-depth interviews (IDIs) were used to collect qualitative data. A random sample of 379 mothers was sufficient to answer the study question. Log-binomial regression model was used to identify factors associated with childbirth at home. RESULTS: A total of 103 (26 %) mothers delivered at home. From the univariate analysis, both mother and the partners old age, being in a polygamy marriage, being a mother of at least two children and staying >=5 Kms radius from the nearest health facility were associated with higher risk of delivering at home (crude P < 0.05). Both mother and partner's higher education level were associated with a protective effect on the risk of delivering at home (RR < 1.0 and P < 0.05). In multivariate regression model, only long distance (>=10Kms) from the nearest health facility was associated with higher risk of delivering at home (adjusted RR 3.86, 95 % CI 2.13 to 7.02). CONCLUSION: From this population, the major reason why mothers still deliver at home is the long distance from nearest health facility. To reduce maternal mortality, access to health facility by pregnant mothers need to be improved. PMID- 26842658 TI - Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review. AB - With a political debate about the potential risks and benefits of cannabis use as a backdrop, the wave of legalization and liberalization initiatives continues to spread. Four states (Colorado, Washington, Oregon, and Alaska) and the District of Columbia have passed laws that legalized cannabis for recreational use by adults, and 23 others plus the District of Columbia now regulate cannabis use for medical purposes. These policy changes could trigger a broad range of unintended consequences, with profound and lasting implications for the health and social systems in our country. Cannabis use is emerging as one among many interacting factors that can affect brain development and mental function. To inform the political discourse with scientific evidence, the literature was reviewed to identify what is known and not known about the effects of cannabis use on human behavior, including cognition, motivation, and psychosis. PMID- 26842659 TI - A role for diatom-like silicon transporters in calcifying coccolithophores. AB - Biomineralization by marine phytoplankton, such as the silicifying diatoms and calcifying coccolithophores, plays an important role in carbon and nutrient cycling in the oceans. Silicification and calcification are distinct cellular processes with no known common mechanisms. It is thought that coccolithophores are able to outcompete diatoms in Si-depleted waters, which can contribute to the formation of coccolithophore blooms. Here we show that an expanded family of diatom-like silicon transporters (SITs) are present in both silicifying and calcifying haptophyte phytoplankton, including some globally important coccolithophores. Si is required for calcification in these coccolithophores, indicating that Si uptake contributes to the very different forms of biomineralization in diatoms and coccolithophores. Significantly, SITs and the requirement for Si are absent from highly abundant bloom-forming coccolithophores, such as Emiliania huxleyi. These very different requirements for Si in coccolithophores are likely to have major influence on their competitive interactions with diatoms and other siliceous phytoplankton. PMID- 26842660 TI - Derivation and Validation of a Quality Indicator to Benchmark In-Hospital Complications Among Injury Admissions. AB - IMPORTANCE: The rate of complications among injury admissions has been estimated to be more than 3 times that observed for general admissions, and complications have been targeted as an important quality-of-care metric. Despite the negative effect of complications on resource use and patient mortality and morbidity, there is no standardized method to benchmark trauma centers in terms of in hospital complications, to our knowledge. OBJECTIVES: To develop a quality indicator (QI) for in-hospital complications that can be used to evaluate the quality of acute injury care and to assess its validity. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective cohort study. The setting was a well established inclusive trauma system in Canada. Participants included all 66 048 moderate or major injury admissions to an adult trauma center between April 1, 2006, and March 31, 2012. The dates of the analysis were January to April 2015. MAIN OUTCOMES AND MEASURES: The primary outcome was the occurrence of at least 1 in-hospital complication. We selected risk-adjustment variables by expert consultation and bootstrap resampling. We evaluated internal validity using measures of discrimination, construct validity, and forecasting. RESULTS: The study cohort comprised 66 048 patients. Their mean (SD) age was 59 (22) years, and 48.0% were female. Fifteen percent of patients had at least 1 in-hospital complication. The risk-adjustment model has excellent discrimination (area under the curve, 0.81) and calibration. The QI was correlated with the risk-adjusted incidence of mortality (r = 0.71), unplanned readmission (r = 0.43), and mean length of stay (r = 0.68). Hospital performance on the QI from 2007 to 2009 was predictive of performance from 2010 to 2012 (r = 0.82). CONCLUSIONS AND RELEVANCE: We developed a QI to benchmark trauma centers on in-hospital complications among injury admissions. The QI is based on data that are routinely collected in most trauma systems and demonstrates good internal validity. The integration of this QI in trauma quality improvement programs will facilitate the identification of quality problems, the implementation of solutions, and the evaluation of their effectiveness. Therefore, the QI has the potential to lead to reductions in mortality, morbidity, and resource use after injury. PMID- 26842661 TI - Haloperidol Suppresses NF-kappaB to Inhibit Lipopolysaccharide-Induced Pro Inflammatory Response in RAW 264 Cells. AB - BACKGROUND Haloperidol, a tranquilizing agent, is administered both to treat symptoms of psychotic disorders and to sedate agitated and delirious patients. Notably, haloperidol has been suggested to inhibit the immune response through unknown mechanisms. We hypothesized that the sedative modulates the immune response via NF-kappaB. MATERIAL AND METHODS Using flow cytometry, we analyzed the effects of haloperidol on expression CD80 and CD86 in RAW 264 cells and in primary macrophages derived from bone marrow. Secretion of interleukin (IL) 1beta, IL-6, and IL-12 p40 was measured by enzyme-linked immunosorbent assay. In addition, NF-kappaB activation was evaluated using a reporter assay based on secretory embryonic alkaline phosphatase. Finally, synthetic antagonists were used to identify the dopamine receptor that mediates the effects of haloperidol. RESULTS Haloperidol inhibited NF-kappaB activation, and thereby suppressed expression of CD80, as well as secretion of IL-1beta, IL-6, and IL-12 p40. CD80 and IL-6 levels were similarly attenuated by a D2-like receptor antagonist, but not by a D1-like receptor antagonist. CONCLUSIONS The data strongly suggest that haloperidol inhibits the immune response by suppressing NF-kB signaling via the dopamine D2 receptor. PMID- 26842662 TI - Anatomical heterogeneity of tendon: Fascicular and interfascicular tendon compartments have distinct proteomic composition. AB - Tendon is a simple aligned fibre composite, consisting of collagen-rich fascicles surrounded by a softer interfascicular matrix (IFM). The composition and interactions between these material phases are fundamental in ensuring tissue mechanics meet functional requirements. However the IFM is poorly defined, therefore tendon structure-function relationships are incompletely understood. We hypothesised that the IFM has a more complex proteome, with faster turnover than the fascicular matrix (FM). Using laser-capture microdissection and mass spectrometry, we demonstrate that the IFM contains more proteins, and that many proteins show differential abundance between matrix phases. The IFM contained more protein fragments (neopeptides), indicating greater matrix degradation in this compartment, which may act to maintain healthy tendon structure. Protein abundance did not alter with ageing, but neopeptide numbers decreased in the aged IFM, indicating decreased turnover which may contribute to age-related tendon injury. These data provide important insights into how differences in tendon composition and turnover contribute to tendon structure-function relationships and the effects of ageing. PMID- 26842663 TI - Surgery for gastroesophageal reflux disease with Gaucher disease type 2. AB - Gaucher disease, the most common lysosomal storage disease, is sometimes complicated with gastroesophageal reflux disease (GERD). The present patient was a 136-day-old Japanese boy with Gaucher disease type 2. Enzyme replacement therapy and chemical chaperone therapy were successful for the skin disorders, joint contractures, hepatosplenomegaly and thrombocytopenia, but he also had GERD. Accordingly, a Nissen fundoplication with gastrostomy was performed. There was no vulnerability of organs, easy bleeding or difficulty of maintaining the visual field because of hepatosplenomegaly during operation. In the perioperative period, there was no prolonged wound healing or infection. GERD was improved. In the near future, the number of long-term survivors of Gaucher disease will increase due to improvements in medical therapy. Therefore, it is expected that the number of patients requiring fundoplication will also increase. In patients with successful medical therapy, surgical fundoplication can be safely and effectively performed. PMID- 26842665 TI - Eight weeks of pre- and postexercise whey protein supplementation increases lean body mass and improves performance in Division III collegiate female basketball players. AB - We examined if 8 weeks of whey protein (WP) supplementation improved body composition and performance measures in NCAA Division III female basketball players. Subjects were assigned to consume 24 g WP (n = 8; age, 20 +/- 2 years; height, 170 +/- 6 cm; weight, 66.0 +/- 3.1 kg) or 24 g of maltodextrin (MD) (n = 6; age, 21 +/- 3 years; height, 169 +/- 6 cm; weight, 68.2 +/- 7.6 kg) immediately prior to and following training (4 days/week anaerobic and resistance training) for 8 weeks. Prior to (T1) and 8 weeks following supplementation (T2), subjects underwent dual X-ray absorptiometry body composition assessment as well as performance tests. The WP group gained lean mass from T1 to T2 (+1.4 kg, p = 0.003) whereas the MD group trended to gain lean mass (+0.4 kg, p = 0.095). The WP group also lost fat mass from T1 to T2 (-1.0 kg, p = 0.003) whereas the MD group did not (-0.5 kg, p = 0.41). The WP group presented greater gains in 1 repetition maximum (1RM) bench press (+4.9 kg) compared with the MD group (+2.3 kg) (p < 0.05). Moreover, the WP group improved agility from T1 to T2 (p = 0.001) whereas the MD group did not (p = 0.38). Both groups equally increased leg press 1RM, vertical jump, and broad jump performances. This study demonstrates that 8 weeks of WP supplementation improves body composition and select performance variables in previously trained female athletes. PMID- 26842664 TI - Neuroinflammation and structural injury of the fetal ovine brain following intra amniotic Candida albicans exposure. AB - BACKGROUND: Intra-amniotic Candida albicans (C. Albicans) infection is associated with preterm birth and high morbidity and mortality rates. Survivors are prone to adverse neurodevelopmental outcomes. The mechanisms leading to these adverse neonatal brain outcomes remain largely unknown. To better understand the mechanisms underlying C. albicans-induced fetal brain injury, we studied immunological responses and structural changes of the fetal brain in a well established translational ovine model of intra-amniotic C. albicans infection. In addition, we tested whether these potential adverse outcomes of the fetal brain were improved in utero by antifungal treatment with fluconazole. METHODS: Pregnant ewes received an intra-amniotic injection of 10(7) colony-forming units C. albicans or saline (controls) at 3 or 5 days before preterm delivery at 0.8 of gestation (term ~ 150 days). Fetal intra-amniotic/intra-peritoneal injections of fluconazole or saline (controls) were administered 2 days after C. albicans exposure. Post mortem analyses for fungal burden, peripheral immune activation, neuroinflammation, and white matter/neuronal injury were performed to determine the effects of intra-amniotic C. albicans and fluconazole treatment. RESULTS: Intra-amniotic exposure to C. albicans caused a severe systemic inflammatory response, illustrated by a robust increase of plasma interleukin-6 concentrations. Cerebrospinal fluid cultures were positive for C. albicans in the majority of the 3-day C. albicans-exposed animals whereas no positive cultures were present in the 5-day C. albicans-exposed and fluconazole-treated animals. Although C. albicans was not detected in the brain parenchyma, a neuroinflammatory response in the hippocampus and white matter was seen which was characterized by increased microglial and astrocyte activation. These neuroinflammatory changes were accompanied by structural white matter injury. Intra-amniotic fluconazole reduced fetal mortality but did not attenuate neuroinflammation and white matter injury. CONCLUSIONS: Intra-amniotic C. albicans exposure provoked acute systemic and neuroinflammatory responses with concomitant white matter injury. Fluconazole treatment prevented systemic inflammation without attenuating cerebral inflammation and injury. PMID- 26842666 TI - Effects of different periods of paradoxical sleep deprivation and sleep recovery on lipid and glucose metabolism and appetite hormones in rats. AB - Sleep has a fundamental role in the regulation of energy balance, and it is an essential and natural process whose precise impacts on health and disease have not yet been fully elucidated. The aim of this study was to assess the consequences of different periods of paradoxical sleep deprivation (PSD) and recovery from PSD on lipid profile, oral glucose tolerance test (OGTT) results, and changes in insulin, corticosterone, ghrelin, and leptin concentrations. Three month-old male Wistar rats weighing 250-350 g were submitted to 24, 96, or 192 h of PSD or 192 h of PSD with 480 h of recovery. The PSD was induced by the multiple platforms method. Subsequently, the animals were submitted to an OGTT. One day later, the animals were killed and the levels of triglycerides, total cholesterol, lipoproteins (low-density lipoprotein, very-low-density lipoprotein, and high-density lipoprotein), insulin, ghrelin, leptin, and corticosterone in plasma were quantified. There was a progressive decrease in body weight with increasing duration of PSD. The PSD induced basal hypoglycemia over all time periods evaluated. Evaluation of areas under the curve revealed progressive hypoglycemia only after 96 and 192 h of PSD. There was an increase in corticosterone levels after 192 h of PSD. We conclude that PSD induces alterations in metabolism that are reversed after a recovery period of 20 days. PMID- 26842667 TI - The acute effect of maximal exercise on central and peripheral arterial stiffness indices and hemodynamics in children and adults. AB - This study compared the effects of a bout of maximal running exercise on arterial stiffness in children and adults. Right carotid blood pressure and artery stiffness indices measured by pulse wave velocity (PWV), compliance and distensibility coefficients, stiffness index alpha and beta (echo-tracking), contralateral carotid blood pressure, and upper and lower limb and central/aortic PWV (applanation tonometry) were taken at rest and 10 min after a bout of maximal treadmill running in 34 children (7.38 +/- 0.38 years) and 45 young adults (25.22 +/- 0.91 years) having similar aerobic potential. Two-by-two repeated measures analysis of variance and analysis of covariance were used to detect differences with exercise between groups. Carotid pulse pressure (PP; eta(2) = 0.394) increased more in adults after exercise (p < 0.05). Compliance (eta(2) = 0.385) decreased in particular in adults and in those with high changes in distending pressure, similarly to stiffness index alpha and beta. Carotid PWV increased more in adults and was related to local changes in PP but not mean arterial pressure (MAP). Stiffness in the lower limbs decreased (eta(2) = 0.115) but apparently only in those with small MAP changes (eta(2) = 0.111). No significant exercise or group interaction effects were found when variables were adjusted to height. An acute bout of maximal exercise can alter arterial stiffness and hemodynamics in the carotid artery and within the active muscle beds. Arterial stiffness and hemodynamic response to metabolic demands during exercise in children simply reflect their smaller body size and may not indicate a particular physiological difference compared with adults. PMID- 26842668 TI - Quantitative Proteomic Analysis Reveals Populus cathayana Females Are More Sensitive and Respond More Sophisticatedly to Iron Deficiency than Males. AB - Previous studies have shown that there are significant sexual differences in the morphological and physiological responses of Populus cathayana Rehder to nitrogen and phosphorus deficiencies, but little is known about the sex-specific differences in responses to iron deficiency. In this study, the effects of iron deficiency on the morphology, physiology, and proteome of P. cathayana males and females were investigated. The results showed that iron deficiency (25 days) significantly decreased height growth, photosynthetic rate, chlorophyll content, and tissue iron concentration in both sexes. A comparison between the sexes indicated that iron-deficient males had less height inhibition and photosynthesis system II or chloroplast ultrastructural damage than iron-deficient females. iTRAQ-based quantitative proteomic analysis revealed that 144 and 68 proteins were decreased in abundance (e.g., proteins involved in photosynthesis, carbohydrate and energy metabolism, and gene expression regulation) and 78 and 39 proteins were increased in abundance (e.g., proteins involved in amino acid metabolism and stress response) according to the criterion of ratio >=1.5 in females and males, respectively. A comparison between the sexes indicated that iron-deficient females exhibited a greater change in the proteins involved in photosynthesis, carbon and energy metabolism, the redox system, and stress responsive proteins. This study reveals females are more sensitive and have a more sophisticated response to iron deficiency compared with males and provides new insights into differential sexual responses to nutrient deficiency. PMID- 26842669 TI - In reply: Confirmation of tracheal intubation time in adults. PMID- 26842670 TI - Evaluation of lead aprons and their maintenance and management at our hospital. AB - Lead aprons are worn by medical workers to reduce the effects of the radiation doses to which they are exposed during radiography and surgery performed with radioscopic apparatus. Regarding the management of such aprons, the Radiation Protection Section of the Japanese Society of Radiological Technology issued the "Guidelines for the Management of Lead Aprons" in 2000, and common management criteria have been set for all institutions. However, we found that the lead aprons used in operating rooms had not been closely inspected before 2014 in our hospital. Thus, we examined the extent of damage of such aprons in our operation room via computed tomography (CT) scout imaging, as well as visual and tactile inspections. Although no abnormality was detected upon visual and tactile inspections, CT images revealed that protective aprons used for 6 years or more had damaged internal radiation shields, thus risking radiation exposure. In response to these results, we fully realized the need to examine the date of the initial use of currently used lead aprons, to routinely perform visual and tactile inspections, and to regularly evaluate the extent of damage to the internal radiation shields via fluoroscopy in cooperation with the radiation management section. PMID- 26842671 TI - Clinical Report: Cognitive decline in a patient with Cardiofaciocutaneous syndrome. AB - Cardiofaciocutaneous Syndrome (CFCS) is a rare genetic syndrome caused by mutations in one of four genes: BRAF, MAP2K1, MAP2K2, and KRAS. There is tremendous phenotypic heterogeneity in patients with CFCS and so confirmation of diagnosis requires genetic testing. Neurologic and/or cognitive symptoms are present in almost all CFCS individuals. Little is known about cognitive function in older patients with CFCS. In this report, we present the cognitive, neuropsychiatric, and imaging findings of a patient diagnosed with CFCS who after having remained stable developed progressive cognitive/behavioral and motor decline. PMID- 26842672 TI - Body mass index and oral health status in Korean adults: the Fifth Korea National Health and Nutrition Examination Survey. AB - OBJECTIVES: The objective of this study was to examine the relationship between body mass index (BMI) and oral health status in Korean adults. METHODS: We used the Fifth Korea National Health and Nutrition Examination Survey to investigate the association between BMI and oral health status. Subjects who were measured for weight and height and had an oral examination in 2010 and 2012 were included (n = 11 466). Using multiple logistic regression analyses adjusted for gender, age, educational level, household income, smoking, frequency of tooth brushing and history of diabetes mellitus, the risk of dental caries and periodontitis was estimated in association with BMI. RESULTS: In the study population, 90.4% had more than one decayed, missing and filled tooth (DMFT) for permanent tooth, and 23.4% had a community periodontal index score (CPI) of 3 or 4. Distribution of underweight, normal weight, overweight and obese was 4.8, 40.5, 22.4 and 32.2%, respectively. Decayed, missing and filled tooth was highest in the normal weight group, and CPI was significantly highest in the obese group. In the overweight and obese groups, the odds ratios for periodontitis (CPI >= 3) were 1.18 [95% confidence interval (CI), 1.01-1.37] before and 1.27 (95% CI, 1.10-1.48) after adjustment for confounding factors. However, the risk for dental caries (DMFT >= 1) was not significantly associated with BMI. CONCLUSIONS: Body mass index was related to periodontitis, but not to dental caries, suggesting that obesity is a risk factor for periodontitis. PMID- 26842674 TI - Temperature-feedback upconversion nanocomposite for accurate photothermal therapy at facile temperature. AB - Photothermal therapy (PTT) at present, following the temperature definition for conventional thermal therapy, usually keeps the temperature of lesions at 42-45 degrees C or even higher. Such high temperature kills cancer cells but also increases the damage of normal tissues near lesions through heat conduction and thus brings about more side effects and inhibits therapeutic accuracy. Here we use temperature-feedback upconversion nanoparticle combined with photothermal material for real-time monitoring of microscopic temperature in PTT. We observe that microscopic temperature of photothermal material upon illumination is high enough to kill cancer cells when the temperature of lesions is still low enough to prevent damage to normal tissue. On the basis of the above phenomenon, we further realize high spatial resolution photothermal ablation of labelled tumour with minimal damage to normal tissues in vivo. Our work points to a method for investigating photothermal properties at nanoscale, and for the development of new generation of PTT strategy. PMID- 26842676 TI - Skin tumor immunity: Site does matter for antigen presentation by DCs. AB - The immune system has the ability to specifically identify and eliminate tumors, but the underlying mechanisms responsible for this phenomenon are not fully understood. A study published in this issue of the European Journal of Immunology now provides new insights into this important problem. Joncker et al. [Eur. J. Immunol. 2016. 46: 609-618] show that the timely mobilization of tumor antigen bearing dendritic cells (DCs) from the periphery to the lymph nodes is critical for effective antitumor T-cell immunity, and that DCs present tumor antigens much more efficiently when encountered in the skin rather than in the subcutaneous tissues. PMID- 26842677 TI - Ultrasound measurement of deep and superficial abdominal muscles thickness during standing postural tasks in participants with and without chronic low back pain. AB - BACKGROUND: Activity of deep abdominal muscles increases the lumbar stability. Majority of previous studies indicated abdominal muscle activity dysfunction during static activity in patients with low back pain (LBP). However, the number of studies that evaluated deep abdominal muscle activity in dynamic standing activities in patients is limited, while this assessment provides better understanding of pain behavior during these activities. OBJECTIVE: Investigation of superficial and deep abdominal muscles activity in participants with chronic LBP as compared to healthy individuals during standing tasks. DESIGN: Case control study. METHODS: Ultrasound imaging was used to measure the thickness of transverse abdominis (TrA), internal oblique (IO) and external oblique (EO) muscles in female participants with (N = 45) and without chronic LBP (CLBP) (N = 45) during tests. The Biodex Balance System was used to provide standing tasks. The thickness of each muscle in a standing task was normalized to actual thickness at rest in the supine lying position to estimate its activity. RESULTS: The results indicate increases in thickness of all muscles in both groups during dynamic as compared to static standing tasks (P < 0.05, ES > 0.5). Lower percentages of thickness change for TrA muscle and higher for EO muscle were found in the patients as compared to healthy individuals during all tests (P < 0.05, ES > 1.28). CONCLUSIONS: Higher activity of superficial than deep abdominal muscles in patients as compared to healthy individuals during standing tasks indicates motor control dysfunction in patients with CLBP. Standing tasks can discriminate the individuals with and without LBP and can be progressively used in training. PMID- 26842675 TI - Reconstruction of the insulin-like signalling pathway of Haemonchus contortus. AB - BACKGROUND: In the present study, we reconstructed the insulin/insulin-like growth factor 1 signalling (IIS) pathway for Haemonchus contortus, which is one of the most important eukaryotic pathogens of livestock worldwide and is related to the free-living nematode Caenorhabditis elegans. METHODS: We curated full length open-reading frames from assembled transcripts, defined the complement of genes that encode proteins involved in this pathway and then investigated the transcription profiles of these genes for all key developmental stages of H. contortus. RESULTS: The core components of the IIS pathway are similar to their respective homologs in C. elegans. However, there is considerable variation in the numbers of isoforms between H. contortus and C. elegans and an absence of AKT 2 and DDL-2 homologs from H. contortus. Interestingly, DAF-16 has a single isoform in H. contortus compared with 12 in C. elegans, suggesting novel functional roles in the parasitic nematode. Some IIS proteins, such as DAF-18 and SGK-1, vary in their functional domains, indicating distinct roles from their homologs in C. elegans. CONCLUSIONS: This study paves the way for the further characterization of key signalling pathways in other socioeconomically important parasites and should help understand the complex mechanisms involved in developmental processes. PMID- 26842678 TI - Depressive Symptoms Negatively Impact Montreal Cognitive Assessment Performance: A Memory Clinic Experience. AB - OBJECTIVE: The Montreal Cognitive Assessment (MoCA) is a general cognitive screening tool that has shown sensitivity in detecting mild levels of cognitive impairment in various clinical populations. Although mood dysfunction is common in referrals to memory clinics, the influence of mood on the MoCA has to date been largely unexplored. METHOD: In this study, we examined the impact of mood dysfunction on the MoCA using a memory clinic sample of individuals with depressive symptoms who did not meet criteria for a neurodegenerative disease. RESULTS: Half of the group with depressive symptoms scored below the MoCA suggested cutoff for cognitive impairment. As a group, they scored below healthy controls, but above individuals with Alzheimer's disease and frontotemporal dementia. A MoCA subtask analysis revealed a pattern of executive/attentional dysfunction in those with depressive symptoms. CONCLUSIONS: This observed negative impact of depressive symptomatology on the MoCA has interpretative implications for its utility as a cognitive screening tool in a memory clinic setting. PMID- 26842681 TI - Layered-MnO2 Nanosheet Grown on Nitrogen-Doped Graphene Template as a Composite Cathode for Flexible Solid-State Asymmetric Supercapacitor. AB - Flexible solid-state supercapacitors provide a promising energy-storage alternative for the rapidly growing flexible and wearable electronic industry. Further improving device energy density and developing a cheap flexible current collector are two major challenges in pushing the technology forward. In this work, we synthesize a nitrogen-doped graphene/MnO2 nanosheet (NGMn) composite by a simple hydrothermal method. Nitrogen-doped graphene acts as a template to induce the growth of layered delta-MnO2 and improves the electronic conductivity of the composite. The NGMn composite exhibits a large specific capacitance of about 305 F g(-1) at a scan rate of 5 mV s(-1). We also create a cheap and highly conductive flexible current collector using Scotch tape. Flexible solid-state asymmetric supercapacitors are fabricated with NGMn cathode, activated carbon anode, and PVA-LiCl gel electrolyte. The device can achieve a high operation voltage of 1.8 V and exhibits a maximum energy density of 3.5 mWh cm(-3) at a power density of 0.019 W cm(-3). Moreover, it retains >90% of its initial capacitance after 1500 cycles. Because of its flexibility, high energy density, and good cycle life, NGMn-based flexible solid state asymmetric supercapacitors have great potential for application in next-generation portable and wearable electronics. PMID- 26842682 TI - [Malignant lymphomas]. PMID- 26842680 TI - Tumor-derived exosomes regulate expression of immune function-related genes in human T cell subsets. AB - Tumor cell-derived exosomes (TEX) suppress functions of immune cells. Here, changes in the gene profiles of primary human T lymphocytes exposed in vitro to exosomes were evaluated. CD4(+) Tconv, CD8(+) T or CD4(+) CD39(+) Treg were isolated from normal donors' peripheral blood and co-incubated with TEX or exosomes isolated from supernatants of cultured dendritic cells (DEX). Expression levels of 24-27 immune response-related genes in these T cells were quantified by qRT-PCR. In activated T cells, TEX and DEX up-regulated mRNA expression levels of multiple genes. Multifactorial data analysis of DeltaCt values identified T cell activation and the immune cell type, but not exosome source, as factors regulating gene expression by exosomes. Treg were more sensitive to TEX-mediated effects than other T cell subsets. In Treg, TEX-mediated down-regulation of genes regulating the adenosine pathway translated into high expression of CD39 and increased adenosine production. TEX also induced up-regulation of inhibitory genes in CD4(+) Tconv, which translated into a loss of CD69 on their surface and a functional decline. Exosomes are not internalized by T cells, but signals they carry and deliver to cell surface receptors modulate gene expression and functions of human T lymphocytes. PMID- 26842684 TI - Expanding Roles in Infection Management. PMID- 26842683 TI - [Current treatment strategies for follicular lymphoma]. AB - In the last few years major changes have taken place in the management of follicular lymphoma (FL) leading to a substantial improvement in the prognosis of patients suffering from this disease. For patients with limited disease stages I and II radiotherapy can lead to long-term remission, while it still remains unclear whether this actually represents a cure; therefore, new approaches are investigating the combination of irradiation with an anti-CD20 antibody. For patients with advanced stages III and IV and a low tumor burden, watch and wait is still the first choice of management. For advanced stages III and IV and a high tumor burden, immunochemotherapy followed by 2 years of rituximab maintenance therapy is the worldwide accepted standard. New antibodies and new agents targeting oncogenic pathways or having immunomodulatory activity provide attractive new therapeutic options, which are currently being explored in clinical phase II/III studies. These approaches provide the perspective to establish chemotherapy-free therapy concepts in the near future. PMID- 26842685 TI - Deep Brain Stimulation and Medication Management in Parkinson's Disease. AB - Current medical treatments for Parkinson's disease (PD) are symptomatic, not curative. Over time, patients need additional medications, increased doses, and increased dosing frequencies to control symptoms. Often, medications lose their effectiveness or side effects become intolerable. Deep brain stimulation (DBS) is a surgical option that, unlike other surgical procedures for PD, is externally adjustable and reversible. DBS is best employed in patients whose symptoms have responded to medication, but escalating doses or dosing frequencies are limiting in some way. During the perioperative period, clinicians must manage medication very carefully. Depending on lead placement and the patient's unique symptom constellation, medication changes are likely. Pharmacists who have a good understanding of the procedure can provide exceptional care and counseling. PMID- 26842686 TI - Oritavancin: A Novel Lipoglycopeptide. AB - OBJECTIVE: To review the pharmacology, pharmacokinetics, drug interactions, microbiologic profile, dosage and administration, safety, clinical efficacy, and potential place in therapy for the new lipoglycopetide, oritavancin. DATA SOURCES: MEDLINE and PubMed searches of available literature in English were conducted for oritavancin. Principal supplementary sources include the Food and Drug Administration (FDA) package insert, and FDA/European Medicines Agency guidances on acute bacterial skin and skin structure infections (ABSSSI). STUDY SELECTION AND DATA EXTRACTION: Information from all stages of clinical development was evaluated to provide an overview of oritavancin, from in vitro susceptibility, to early human studies, to the latter stages of clinical trials. DATA SYNTHESIS: Oritavancin is a lipoglycopeptide antibiotic that has a mechanism of action and broad-spectrum gram-positive coverage similar to other glycopeptides. Compared with other glycopeptides, oritavancin minimum inhibitory concentrations tend to be lower. Oritavancin also has coverage against glycopeptide-resistant gram-positive organisms. Oritavancin does not require dose adjustment for mild-to-moderate hepatic or renal impairment, and its prolonged half-life of 245 hours allows for a one-time administration in the treatment of ABSSSI. In phase 2 and 3 clinical trials, oritavancin was shown to be well tolerated in addition to being noninferior to vancomycin for the treatment of ABSSSI. The most common side effects experienced were gastrointestinal in nature. CONCLUSIONS: Oritavancin was approved by FDA for the treatment of ABSSSI in August 2014 and is marketed under the trade name Orbactiv. Its reduced dosing and monitoring requirements and efficacy against resistant gram-positive pathogens provide a unique profile that distinguishes it from current options in the treatment of ABSSSI. PMID- 26842679 TI - Antenatal Betamethasone for Women at Risk for Late Preterm Delivery. AB - BACKGROUND: Infants who are born at 34 to 36 weeks of gestation (late preterm) are at greater risk for adverse respiratory and other outcomes than those born at 37 weeks of gestation or later. It is not known whether betamethasone administered to women at risk for late preterm delivery decreases the risks of neonatal morbidities. METHODS: We conducted a multicenter, randomized trial involving women with a singleton pregnancy at 34 weeks 0 days to 36 weeks 5 days of gestation who were at high risk for delivery during the late preterm period (up to 36 weeks 6 days). The participants were assigned to receive two injections of betamethasone or matching placebo 24 hours apart. The primary outcome was a neonatal composite of treatment in the first 72 hours (the use of continuous positive airway pressure or high-flow nasal cannula for at least 2 hours, supplemental oxygen with a fraction of inspired oxygen of at least 0.30 for at least 4 hours, extracorporeal membrane oxygenation, or mechanical ventilation) or stillbirth or neonatal death within 72 hours after delivery. RESULTS: The primary outcome occurred in 165 of 1427 infants (11.6%) in the betamethasone group and 202 of 1400 (14.4%) in the placebo group (relative risk in the betamethasone group, 0.80; 95% confidence interval [CI], 0.66 to 0.97; P=0.02). Severe respiratory complications, transient tachypnea of the newborn, surfactant use, and bronchopulmonary dysplasia also occurred significantly less frequently in the betamethasone group. There were no significant between-group differences in the incidence of chorioamnionitis or neonatal sepsis. Neonatal hypoglycemia was more common in the betamethasone group than in the placebo group (24.0% vs. 15.0%; relative risk, 1.60; 95% CI, 1.37 to 1.87; P<0.001). CONCLUSIONS: Administration of betamethasone to women at risk for late preterm delivery significantly reduced the rate of neonatal respiratory complications. (Funded by the National Heart, Lung, and Blood Institute and the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT01222247.). PMID- 26842687 TI - Treatment of Dry Eye Disease. AB - OBJECTIVE: Review of the etiology, clinical manifestations, and treatment of dry eye disease (DED). DATA SOURCES: Articles indexed in PubMed (National Library of Medicine), Iowa Drug Information Service (IDIS), and the Cochrane Reviews and Trials in the last 10 years using the key words "dry eye disease," "dry eye syndrome," "dry eye and treatment." Primary sources were used to locate additional resources. STUDY SELECTION AND DATA EXTRACTION: Sixty-eight publications were reviewed, and criteria supporting the primary objective were used to identify useful resources. DATA SYNTHESIS: The literature included practice guidelines, book chapters, review articles, original research articles, and product prescribing information for the etiology, clinical manifestations, diagnosis, and treatment of DED. CONCLUSION: DED is one of the most common ophthalmic disorders. Signs and symptoms of DED vary by patient, but may include ocular irritation, redness, itching, photosensitivity, visual blurring, mucous discharge, and decreased tear meniscus or break-up time. Symptoms improve with treatment, but the condition is not completely curable. Treatment includes reducing environmental causes, discontinuing medications that cause or worsen dry eye, and managing contributing ocular or systemic conditions. Most patients use nonprescription tear substitutes, and if these are not sufficient, other treatment is prescribed. These treatments include the ophthalmic anti inflammatory agent cyclosporine, punctal occlusion, eye side shields, systemic cholinergic agents, and autologous serum tears. This article reviews the etiology, symptoms, and current therapy for DED. PMID- 26842688 TI - Assisted Living Facilities: The Next Frontier for Consultant Pharmacists. AB - Consultant pharmacists improve the lives of older adults by providing medication management, avoiding adverse drug reactions, and uncovering duplicative therapy. Despite this, there is a lack of legislation supporting the role of the consultant pharmacist in many of the settings-other than nursing facilities-where seniors reside. Specifically, federal and state laws do not recognize consultant pharmacists for their specialized role in pharmacotherapy and the potential benefits they bring to older adults in assisted living facilities. Among many services, consultant pharmacists may provide monthly medication reviews, staff medication education, and medication system management in assisted living facilities. A literature search was conducted to identify literature supporting the benefits of consultant pharmacists in assisted living facilities. Gaps in available literature are discussed as are ideas for expanding the role of consultant pharmacists in assisted living facilities. PMID- 26842689 TI - Development and Assessment of a Medication Safety Measurement Program in a Long Term Care Pharmacy. AB - OBJECTIVE: Medication errors continue to be a major issue in the health care system, including in long-term care facilities. While many hospitals and health systems have developed methods to identify, track, and prevent these errors, long term care facilities historically have not invested in these error-prevention strategies. The objective of this study was two-fold: 1) to develop a set of medication-safety process measures for dispensing in a long-term care pharmacy, and 2) to analyze the data from those measures to determine the relative safety of the process. DESIGN/SETTING/PARTICIPANTS: The study was conducted at In Touch Pharmaceuticals in Valparaiso, Indiana. To assess the safety of the medication use system, each step was documented using a comprehensive flowchart (process flow map) tool. Once completed and validated, the flowchart was used to complete a "failure modes and effects analysis" (FMEA) identifying ways a process may fail. Operational gaps found during FMEA were used to identify points of measurement. The research identified a set of eight measures as potential areas of failure; data were then collected on each one of these. RESULTS: More than 133,000 medication doses (opportunities for errors) were included in the study during the research time frame (April 1, 2014, and ended on June 4, 2014). Overall, there was an approximate order-entry error rate of 15.26%, with intravenous errors at 0.37%. A total of 21 errors migrated through the entire medication-use system. These 21 errors in 133,000 opportunities resulted in a final check error rate of 0.015%. CONCLUSION: A comprehensive medication-safety measurement program was designed and assessed. This study demonstrated the ability to detect medication errors in a long-term pharmacy setting, thereby making process improvements measureable. Future, larger, multi-site studies should be completed to test this measurement program. PMID- 26842690 TI - The 2016 Elections, ASCP's Policy Agenda, and Grassroots Activity. PMID- 26842691 TI - Outcomes of Triple-Negative Breast Cancers (TNBC) Compared with Non-TNBC: Does the Survival Vary for All Stages? AB - BACKGROUND: Triple-negative breast cancer (TNBC) is associated with aggressive tumor behavior and worse outcomes. In a study at a tertiary care breast unit in a developing country, clinico-pathological attributes and outcomes of patients with TNBC were compared with (c.w.) ER, PR, and/or HER2 expressing tumors (non-TNBC). PATIENTS AND METHODS: Medical records of 1213 consecutive breast cancer patients managed during 2004-2010 were reviewed. An evaluable cohort of 705 patients with complete treatment and follow-up (median 36 months) information was thus identified. Patients were categorized per ER, PR & HER2 status into TNBC, and ER/PR+ and/or HER2+ groups. Clinico-pathological parameters, response to NACT, and OS & DFS were compared between TNBC and non-TNBC groups. RESULTS: TNBC patients (n = 249) comprised 35.3 % of the study cohort (n = 705), and were significantly younger than non-TNBC patients (mean age 49.1 +/- 11.2y c.w. 51.8 +/- 11.3, p = 0.02). The TNM stage at presentation was similar in the two groups (Stage I and II-37 % c.w. 44.3 %, Stage III-47.5 % c.w. 39.5 %, Stage IV-15.5 % c.w. 16.2 % in TNBC c.w. Non-TNBC; p = 0.09). Tumor size (5.7 +/- 2.9 cm TNBC c.w. 5.4 +/- 2.8 cm non-TNBC, p = 0.22) was similar but lymph nodal (cN) metastases were more frequent in TNBC (77.3 % c.w. 69.8 %; p = 0.03). TNBC had higher histologic grade (97.1 % gr II/III in TNBC c.w. 91.2 % non-TNBC, p = 0.01) and higher incidence of LVI (20.4 % in TNBC c.w. 13.5 %, p = 0.03). Patient groups received similar multi-disciplinary surgical, radiation, and systemic treatment. Comparable proportion of patients in 2 groups were treated with NACT (42 % c.w. 38 %), which resulted in pathological complete response (pCR) in 27.5 % TNBC patients c.w. 17.1 % non-TNBC patients (p = 0.04). Both OS (81.8 +/- 4.52 c.w. 97.90 +/- 3.87 months, p < 0.001) and DFS (89.2 +/- 5.1 c.w. 113.8 +/- 4.3 months, p < 0.001) were shorter in TNBC than non-TNBC group. On stage-wise comparison, OS differed significantly only in stage III (47.4 +/- 5.3 months in TNBC c.w. 74.5 +/- 4.4 in non-TNBC; p < 0.001). Univariate and multivariate analyses revealed tumor stage and IHC subtyping into TNBC c.w. non-TNBC as most important factors predictive of survival. CONCLUSIONS: TNBC occurred at younger age and exhibited aggressive pathology as compared to non-TNBC patients. Although patients with TNBC exhibited better chemo-sensitivity, they had worse DFS and OS compared to the non-TNBC patients. The survival of Stage III TNBC patients was significantly worse compared to non-TNBC group; while in stages I, II, and IV, survival were not significantly different. PMID- 26842693 TI - Laparoscopic Stapled Cardioplasty-Room for Improvement. PMID- 26842692 TI - IV Acetaminophen Results in Lower Hospital Costs and Emergency Room Visits Following Bariatric Surgery: a Double-Blind, Prospective, Randomized Trial in a Single Accredited Bariatric Center. AB - BACKGROUND: Postoperative pain control in bariatric surgery is challenging, despite use of intravenous (IV) narcotics. IV acetaminophen is one pain control alternative. OBJECTIVE: The aim of this study was to investigate the economic impact of IV acetaminophen in bariatric surgery and its effect on patients' pain, satisfaction, and hospital length of stay. METHODS: In a randomized controlled trial, Group 1 (treatment) received IV acetaminophen plus IV narcotics 30 min before surgery, then medication plus IV narcotics/PO narcotics for the remaining 18 h. Group 2 (control) received IV normal saline plus IV/PO narcotics. Patients underwent laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (SG). Primary outcomes included direct hospital costs, length of stay, postoperative pain, and patient satisfaction. Secondary outcomes included indirect costs, rescue narcotics dosage, and 30-day outcomes. RESULTS: Mean direct hospital cost in the treatment group (n = 50) was $3089.18 versus $2991.62 for the control group (n = 50) (p > 0.05). Pain scores did not differ significantly (p = 0.61). After adjusting for surgery type, there was no significant difference in length of stay (p = 0.95). Significantly more control group patients incurred surgery-related indirect costs (10 versus 2%, p < 0.05), with greater presentation to the emergency department (ED) for abdominal pain (5/50 versus 1/50), yielding higher total indirect costs ($39,293 versus $13,185). CONCLUSIONS: Using IV acetaminophen for postoperative pain management produced notable indirect cost savings and reduced ED visits in the first 30 days postoperatively, with good safety and tolerance. Decreased statistical power may have accounted for certain non-significant findings. PMID- 26842694 TI - Effects of a Web-Based Computer-Tailored Game to Reduce Binge Drinking Among Dutch Adolescents: A Cluster Randomized Controlled Trial. AB - BACKGROUND: Binge drinking among Dutch adolescents is among the highest in Europe. Few interventions so far have focused on adolescents aged 15 to 19 years. Because binge drinking increases significantly during those years, it is important to develop binge drinking prevention programs for this group. Web-based computer-tailored interventions can be an effective tool for reducing this behavior in adolescents. Embedding the computer-tailored intervention in a serious game may make it more attractive to adolescents. OBJECTIVE: The aim was to assess whether a Web-based computer-tailored intervention is effective in reducing binge drinking in Dutch adolescents aged 15 to 19 years. Secondary outcomes were reduction in excessive drinking and overall consumption during the previous week. Personal characteristics associated with program adherence were also investigated. METHODS: A cluster randomized controlled trial was conducted among 34 Dutch schools. Each school was randomized into either an experimental (n=1622) or a control (n=1027) condition. Baseline assessment took place in January and February 2014. At baseline, demographic variables and alcohol use were assessed. Follow-up assessment of alcohol use took place 4 months later (May and June 2014). After the baseline assessment, participants in the experimental condition started with the intervention consisting of a game about alcohol in which computer-tailored feedback regarding motivational characteristics was embedded. Participants in the control condition only received the baseline questionnaire. Both groups received the 4-month follow-up questionnaire. Effects of the intervention were assessed using logistic regression mixed models analyses for binge and excessive drinking and linear regression mixed models analyses for weekly consumption. Factors associated with intervention adherence in the experimental condition were explored by means of a linear regression model. RESULTS: In total, 2649 adolescents participated in the baseline assessment. At follow-up, 824 (31.11%) adolescents returned. The intervention was effective in reducing binge drinking among adolescents aged 15 years (P=.03) and those aged 16 years when they participated in at least 2 intervention sessions (P=.04). Interaction effects between excessive drinking and educational level (P=.08) and between weekly consumption and age (P=.09) were found; however, in-depth analyses revealed no significant subgroup effects for both interaction effects. Additional analyses revealed that prolonged use of the intervention was associated with stronger effects for binge drinking. Yet, overall adherence to the intervention was low. Analyses revealed that being Protestant, female, younger, a nonbinge drinker, and having a higher educational background were associated with adherence. CONCLUSIONS: The intervention was effective for adolescents aged 15 and 16 years concerning binge drinking. Prevention messages may be more effective for those at the start of their drinking career, whereas other methods may be needed for those with a longer history of alcohol consumption. Despite using game elements, intervention completion was low. TRIAL REGISTRATION: Dutch Trial Register: NTR4048; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4048 (Archived by WebCite(r) at http://www.webcitation.org/6eSJD3FiY). PMID- 26842695 TI - Joint Model of Iron and Hepcidin During the Menstrual Cycle in Healthy Women. AB - Hepcidin regulates serum iron levels, and its dosage is used in differential diagnostic of iron-related pathologies. We used the data collected in the HEPMEN (named after HEPcidin during MENses) study to investigate the joint dynamics of serum hepcidin and iron during the menstrual cycle in healthy women. Ninety menstruating women were recruited after a screening visit. Six fasting blood samples for determination of iron-status variables were taken in the morning throughout the cycle, starting on the second day of the period. Non-linear mixed effect models were used to describe the evolution of iron and hepcidin. Demographic and medical covariates were tested for their effect on model parameters. Parameter estimation was performed using the SAEM algorithm implemented in the Monolix software. A general pattern was observed for both hepcidin and iron, consisting of an initial decrease during menstruation, followed by a rebound and stabilising during the second half of the cycle. We developed a joint model including a menstruation-induced decrease of both molecules at the beginning of the menses and a rebound effect after menses. Iron stimulated the release of hepcidin. Several covariates, including contraception, amount of blood loss and ferritin, were found to influence the parameters. The joint model of iron and hepcidin was able to describe the fluctuations induced by blood loss from menstruation in healthy non-menopausal women and the subsequent regulation. The HEPMEN study showed fluctuations of iron-status variables during the menstrual cycle, which should be considered when using hepcidin measurements for diagnostic purposes in women of child-bearing potential. PMID- 26842696 TI - Autologous cytokine-induced killer cell transfusion increases overall survival in advanced pancreatic cancer. AB - BACKGROUND: Advanced pancreatic cancer (PC) has very poor prognosis with present treatments, thus necessitating continued efforts to find improved therapeutic approaches. Both preclinical and preliminary clinical data indicate that cytokine induced killer (CIK) cells are an effective tool against various types of solid tumors. Here, we conducted a study to determine whether CIK cell-based therapy (CBT) can improve the outcomes of advanced PC. METHODS: Eighty-two patients with advanced PC, whose predicted survival time was longer than 3 months, were analyzed retrospectively. Of all the patients, 57 individuals were receiving chemotherapy, while the remaining 25 individuals were treated with CBT. RESULTS: The overall survival analysis was based on 48 deaths in the 57 patients in the chemotherapy group (84.2%) and 18 deaths in the 25 patients in the CBT group (72.0%). In the CBT group, the median overall survival time was 13.5 months, as compared to 6.6 months in the chemotherapy group (hazard ratio for death, 0.39; 95% confidence interval, 0.23 to 0.65; p < 0.001). The survival rate was 88.9% in the CBT group versus 54.2% in the chemotherapy group at 6 months, 61.1% versus 12.5% at 12 months, and 38.9% versus 4.2% at 18 months. The disease control rate was 68.0% in the CBT group and 29.8% in the chemotherapy group (p < 0.001). CONCLUSIONS: These results from this retrospective analysis appeared to imply that CBT might prolong survival in these high-risk PC patients. Prospective study is needed to corroborate this observation. PMID- 26842697 TI - Ratios of central venous-to-arterial carbon dioxide content or tension to arteriovenous oxygen content are better markers of global anaerobic metabolism than lactate in septic shock patients. AB - BACKGROUND: To evaluate the ability of the central venous-to-arterial CO2 content and tension differences to arteriovenous oxygen content difference ratios (?ContCO2/?ContO2 and ?PCO2/?ContO2, respectively), blood lactate concentration, and central venous oxygen saturation (ScvO2) to detect the presence of global anaerobic metabolism through the increase in oxygen consumption (VO2) after an acute increase in oxygen supply (DO2) induced by volume expansion (VO2/DO2 dependence). METHODS: We prospectively studied 98 critically ill mechanically ventilated patients in whom a fluid challenge was decided due to acute circulatory failure related to septic shock. Before and after volume expansion (500 mL of colloid solution), we measured cardiac index, VO2, DO2, ?ContCO2/?ContO2 and ?PCO2/?ContO2 ratios, lactate, and ScvO2. Fluid-responders were defined as a >=15 % increase in cardiac index. Areas under the receiver operating characteristic curves (AUC) were determined for these variables. RESULTS: Fifty-one patients were fluid-responders (52 %). DO2 increased significantly (31 +/- 12 %) in these patients. An increase in VO2 >= 15 % ("VO2 responders") concurrently occurred in 57 % of the 51 fluid-responders (45 +/- 16 %). Compared with VO2-non-responders, VO2-responders were characterized by higher lactate levels and higher ?ContCO2/?ContO2 and ?PCO2/?ContO2 ratios. At baseline, lactate predicted a fluid-induced increase in VO2 >= 15 % with AUC of 0.745. Baseline ?ContCO2/?ContO2 and ?PCO2/?ContO2 ratios predicted an increase of VO2 >= 15 % with AUCs of 0.965 and 0.962, respectively. Baseline ScvO2 was not able to predict an increase of VO2 >= 15 % (AUC = 0.624). CONCLUSIONS: ?ContCO2/?ContO2 and ?PCO2/?ContO2 ratios are more reliable markers of global anaerobic metabolism than lactate. ScvO2 failed to predict the presence of global tissue hypoxia. PMID- 26842698 TI - PreImplantation factor prevents atherosclerosis via its immunomodulatory effects without affecting serum lipids. AB - PreImplantation factor (PIF) is a 15-amino acid peptide endogenously secreted by viable embryos, regulating/enabling maternal (host) acceptance/tolerance to the "invading" embryo (allograft) all-while preserving maternal immunity to fight infections. Such attributes make PIF a potential therapeutic agent for chronic inflammatory diseases. We investigated whether PIF's immunomodulatory properties prevent progression of atherosclerosis in the hyper-cholesterolaemic ApoE deficient murine model. Male, high-fat diet fed, ApoE-deficient (ApoE-/-) mice were administered either PBS, scrambled PIF (0.3-3 mg/kg) or PIF (0.3-3 mg/kg) for seven weeks. After treatment, PIF (3 mg/kg)-treated ApoE-/- mice displayed significantly reduced atherosclerosis lesion burden in the aortic sinus and aortic arch, without any effect on lipid profile. PIF also caused a significant reduction in infiltration of macrophages, decreased expression of pro inflammatory adhesion molecules, cytokines and chemokines in the plaque, and reduced circulating IFN-gamma levels. PIF preferentially binds to monocytes/neutrophils. In vitro, PIF attenuated monocyte migration (MCP-1-induced chemotaxis assay) and in vivo in LPS peritonitis model. Also PIF prevented leukocyte extravasation (peritonitis thioglycollate-induced model), demonstrating that PIF exerts its effect in part by modulation of monocyte function. Inhibition of the potassium channel KCNAB3 (Kv1.3) and of the insulin degrading enzyme (IDE) was demonstrated as potential mechanism of PIF's immunomodulatory effects. In conclusion, PIF regulates/lowers inflammation and prevents atherosclerosis development without affecting circulating lipids. Overall our findings establish PIF as a strong immunomodulatory drug candidate for atherosclerosis therapy. PMID- 26842699 TI - Cav 1.3 (CACNA1D) L-type Ca2+ channel dysfunction in CNS disorders. AB - Cav 1.3 belongs to the family of voltage-gated L-type Ca2+ channels and is encoded by the CACNA1D gene. Cav 1.3 channels are not only essential for cardiac pacemaking, hearing and hormone secretion but are also expressed postsynaptically in neurons, where they shape neuronal firing and plasticity. Recent findings provide evidence that human mutations in the CACNA1D gene can confer risk for the development of neuropsychiatric disease and perhaps also epilepsy. Loss of Cav 1.3 function, as shown in knock-out mouse models and by human mutations, does not result in neuropsychiatric or neurological disease symptoms, whereas their acute selective pharmacological activation results in a depressive-like behaviour in mice. Therefore it is likely that CACNA1D mutations enhancing activity may be disease relevant also in humans. Indeed, whole exome sequencing studies, originally prompted to identify mutations in primary aldosteronism, revealed de novo CACNA1D missense mutations permitting enhanced Ca2+ signalling through Cav 1.3. Remarkably, apart from primary aldosteronism, heterozygous carriers of these mutations also showed seizures and neurological abnormalities. Different missense mutations with very similar gain-of-function properties were recently reported in patients with autism spectrum disorders (ASD). These data strongly suggest that CACNA1D mutations enhancing Cav 1.3 activity confer a strong risk for - or even cause - CNS disorders, such as ASD. PMID- 26842700 TI - Comparison of Fecal Microbiota between German Holstein Dairy Cows with and without Left-Sided Displacement of the Abomasum. AB - One of the most common diseases in high-performance German Holstein dairy cows is left-sided displacement of the abomasum (LDA). Hypomotility of the abomasum is detrimental during the pathogenesis of LDA. It is known that improper interactions between the gut microbiota and the enteric nervous system contribute to dysfunctions of gastrointestinal motility. Therefore, we hypothesized that the gut microbial composition will be different between German Holstein dairy cows with and without LDA. We used 16S rRNA gene analysis to evaluate whether there are any differences in bacterial composition between German Holstein dairy cows with and without LDA. Even though our data are limited to being used to correlate compositional changes with corresponding functional aspects in the pathogenesis of LDA, results from this study show that the fecal microbial compositions of German Holstein dairy cows with LDA shifted and were less diverse than those in normal cows. In particular,Spirochaeteswere absent in cows with LDA. PMID- 26842701 TI - Accurate Serodetection of Asymptomatic Leishmania donovani Infection by Use of Defined Antigens. AB - Infection with Leishmania donovaniis typically asymptomatic, but a significant number of individuals may progress to visceral leishmaniasis (VL), a deadly disease that threatens 200 million people in areas where it is endemic. While diagnosis of acute VL has been simplified by the use of cost-effective confirmatory serological tests, similar standardized tools are not widely available for detecting asymptomatic infection, which can be 4 to 20 times more prevalent than active disease. A simple and accurate serological test that is capable of detecting asymptomaticL. donovaniinfection will be useful for surveillance programs targeting VL control and elimination. To address this unmet need, we evaluated recombinant antigens for their ability to detect serum antibodies in 104 asymptomaticL. donovani-infected individuals (qualified as positive forL. donovani-specific antibodies by direct agglutination test [DAT]) from the Mymensingh district of Bangladesh where VL is hyperendemic. The novel proteins rKR95 and rTR18 possessed the greatest potential and detected 69% of DAT positive individuals, with rKR95 being more robust in reactivity. Agreement in results for individuals with high DAT responses, who are more likely to progress to VL disease, was 74%. When considered along with rK39, a gold standard antigen that is used to confirm clinical diagnosis of VL but that is now becoming widely used for surveillance, rKR95 and rTR18 conferred a sensitivity of 84% based on a theoretical combined estimate. Our data indicate that incorporating rKR95 and rTR18 with rK39 in serological tests amenable to rapid or high-throughput screening may enable simple and accurate detection of asymptomatic infection. Such tests will be important tools to measureL. donovaniinfection rates, a primary goal in surveillance and a critical measurement with which to assess elimination programs. PMID- 26842702 TI - Evaluation of Performance Characteristics of the Aptima HIV-1 Quant Dx Assay for Detection and Quantitation of Human Immunodeficiency Virus Type 1 in Plasma and Cervicovaginal Lavage Samples. AB - Quantification of HIV-1 RNA has become the standard of care in the clinical management of HIV-1-infected individuals. The objective of this study was to evaluate performance characteristics and relative workflow of the Aptima HIV-1 Quant Dx assay in comparison with the Abbott RealTime HIV-1 assay using plasma and cervicovaginal lavage (CVL) specimens. Assay performance was evaluated by using an AcroMetrix HIV-1 panel, AcroMetrix positive controls, Qnostics and SeraCare HIV-1 evaluation panels, 208 clinical plasma samples, and 205 matched CVL specimens on the Panther and m2000 platforms. The Aptima assay demonstrated good linearity over the quantification range tested (2 to 5 log10copies/ml), and there was strong linear correlation between the assays (R(2)= 0.99), with a comparable coefficient of variance of <5.5%. For the plasma samples, Deming regression analyses and Bland-Altman plots showed excellent agreement between the assays, with an interassay concordance of 91.35% (kappa = 0.75; 95% confidence interval [CI], 0.65 to 0.85), and on average, the viral loads determined by the Aptima assay were 0.21 log10copies/ml higher than those determined by the RealTime assay. The assays differed in their sensitivity for quantifying HIV-1 RNA loads in CVL samples, with the Aptima and RealTime assays detecting 30% and 20%, respectively. Aptima had fewer invalid results, and on average, the viral loads in CVL samples quantified by the Aptima assay were 0.072 log10copies/ml higher than those of the RealTime assay. Our results demonstrate that the Aptima assay is sensitive and accurate in quantifying viral loads in both plasma and CVL specimens and that the fully automated Panther system has all the necessary features suitable for clinical laboratories demanding high-throughput sample processing. PMID- 26842703 TI - Evaluation of Liquid-Based Swab Transport Systems against the New Approved CLSI M40-A2 Standard. AB - Following revised information pertaining to newer swab types and testing protocols in the new CLSI M40-A2 standard, we evaluated three liquid swab transport systems for the recovery of aerobic, anaerobic, and fastidious organisms at room temperature and at 4 degrees C. All tested liquid swab transport systems were fully compliant with the M40-A2 standard, with acceptable performance at both temperatures after the full specified holding period, using both qualitative (roll-plate) and quantitative (swab elution) methods. PMID- 26842704 TI - Evaluation of MALDI Biotyper Mycobacteria Library v3.0 for Identification of Nontuberculous Mycobacteria. AB - Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has demonstrated its ability to promptly identify nontuberculous mycobacteria using the Mycobacteria Library v2.0. However, some species are particularly difficult to identify reliably using this database, providing a low log(score). In this study, the identification power of an updated Mycobacteria Library (v3.0) has been evaluated. Overall, 109 NTM isolates were analyzed with both databases. The v3.0 database allowed a high-level confidence in the identification [log(score) value, >=1.8] of 91.7% of the isolates versus 83.5% with the v2.0 version (P< 0.01). PMID- 26842705 TI - U.S. Ebola Treatment Center Clinical Laboratory Support. AB - Fifty-five hospitals in the United States have been designated Ebola treatment centers (ETCs) by their state and local health authorities. Designated ETCs must have appropriate plans to manage a patient with confirmed Ebola virus disease (EVD) for the full duration of illness and must have these plans assessed through a CDC site visit conducted by an interdisciplinary team of subject matter experts. This study determined the clinical laboratory capabilities of these ETCs. ETCs were electronically surveyed on clinical laboratory characteristics. Survey responses were returned from 47 ETCs (85%). Forty-one (87%) of the ETCs planned to provide some laboratory support (e.g., point-of-care [POC] testing) within the room of the isolated patient. Forty-four (94%) ETCs indicated that their hospital would also provide clinical laboratory support for patient care. Twenty-two (50%) of these ETC clinical laboratories had biosafety level 3 (BSL-3) containment. Of all respondents, 34 (72%) were supported by their jurisdictional public health laboratory (PHL), all of which had available BSL-3 laboratories. Overall, 40 of 44 (91%) ETCs reported BSL-3 laboratory support via their clinical laboratory and/or PHL. This survey provided a snapshot of the laboratory support for designated U.S. ETCs. ETCs have approached high-level isolation critical care with laboratory support in close proximity to the patient room and by distributing laboratory support among laboratory resources. Experts might review safety considerations for these laboratory testing/diagnostic activities that are novel in the context of biocontainment care. PMID- 26842707 TI - Controlled Evaluation of the New BacT/Alert Virtuo Blood Culture System for Detection and Time to Detection of Bacteria and Yeasts. AB - We compared the newly approved BacT/Alert Virtuo blood culture system to the BacT/Alert 3D system using 115 clinical bacterial and fungal isolates in 784 simulated blood culture bottles. The time to detection was reduced by roughly 20% in the Virtuo system (P< 0.0001) while the detection rate did not differ. PMID- 26842706 TI - Evaluation of Polymorphic Locus Sequence Typing for Candida glabrata Epidemiology. AB - The opportunistic yeast Candida glabratais increasingly refractory to antifungal treatment or prophylaxis and relatedly is increasingly implicated in health care associated infections. To elucidate the epidemiology of these infections, strain typing is required. Sequence-based typing provides multiple advantages over length-based methods, such as pulsed-field gel electrophoresis (PFGE); however, conventional multilocus sequence typing (targeting 6 conserved loci) and whole genome sequencing are impractical for routine use. A commercial sequence-based typing service for C. glabratathat targets polymorphic tandem repeat-containing loci has recently been developed. These CgMT-J and CgMT-M services were evaluated with 56 epidemiologically unrelated isolates, 4 to 7 fluconazole-susceptible or fluconazole-resistant isolates from each of 5 center A patients, 5 matched pairs of fluconazole-susceptible/resistant isolates from center B patients, and 7 isolates from a center C patient who responded to then failed caspofungin therapy. CgMT-J and CgMT-M generated congruent results, resolving isolates into 24 and 20 alleles, respectively. Isolates from all but one of the center A patients shared the same otherwise rare alleles, suggesting nosocomial transmission. Unexpectedly, Pdr1 sequencing showed that resistance arose independently in each patient. Similarly, most isolates from center B also clustered together; however, this may reflect a dominant clone since their alleles were shared by multiple unrelated isolates. Although distinguishable by their echinocandin susceptibilities, all isolates from the center C patient shared alleles, in agreement with the previously reported relatedness of these isolates based on PFGE. Finally, we show how phylogenetic clusters can be used to provide surrogate parents to analyze the mutational basis for antifungal resistance. PMID- 26842709 TI - Corrigendum: Gravity-driven postseismic deformation following the Mw 6.3 2009 L'Aquila (Italy) earthquake. PMID- 26842710 TI - Steroid-responsive painful ophthalmoplegia: Tolosa-Hunt syndrome, Eales disease, or both? AB - Introduction Tolosa-Hunt syndrome (THS) is one of the most common 'benign' causes of painful ophthalmoplegia. Diagnosis is based on clinical and imaging findings and the exclusion of other causes because there is no specific biomarker for the syndrome. Eales disease, an idiopathic inflammatory venous disease that primarily affects the eye, can also affect the central (as stroke or myelitis) and peripheral nervous system. Case report We report the case of a 32-year-old woman with a subacute left ophthalmoplegia and evidence of a gadolinium-enhanced lesion suggesting an inflammatory granuloma that resolved within 48 hours after treatment with steroids. A diagnosis of THS was considered at this time. On a follow-up ophthalmological examination, a diagnosis of Eales disease with involvement of the left eye was made. The patient was treated successfully. Conclusion Eales disease could be a cause of painful ophthalmoplegia and may mimic THS. Long-term follow-up of patients diagnosed with THS may be necessary to exclude other diagnoses. PMID- 26842708 TI - Cancer-associated SF3B1 mutations affect alternative splicing by promoting alternative branchpoint usage. AB - Hotspot mutations in the spliceosome gene SF3B1 are reported in ~20% of uveal melanomas. SF3B1 is involved in 3'-splice site (3'ss) recognition during RNA splicing; however, the molecular mechanisms of its mutation have remained unclear. Here we show, using RNA-Seq analyses of uveal melanoma, that the SF3B1(R625/K666) mutation results in deregulated splicing at a subset of junctions, mostly by the use of alternative 3'ss. Modelling the differential junctions in SF3B1(WT) and SF3B1(R625/K666) cell lines demonstrates that the deregulated splice pattern strictly depends on SF3B1 status and on the 3'ss sequence context. SF3B1(WT) knockdown or overexpression do not reproduce the SF3B1(R625/K666) splice pattern, qualifying SF3B1(R625/K666) as change-of function mutants. Mutagenesis of predicted branchpoints reveals that the SF3B1(R625/K666)-promoted splice pattern is a direct result of alternative branchpoint usage. Altogether, this study provides a better understanding of the mechanisms underlying splicing alterations induced by mutant SF3B1 in cancer, and reveals a role for alternative branchpoints in disease. PMID- 26842711 TI - The relationship between serum adipocytokines and Graves' ophthalmopathy: A hospital-based study. AB - Adipocytokines are thought to be associated with inflammatory disorders and autoimmune diseases. However, limited information is available on the relationship between serum adipocytokine levels, Graves' disease (GD), and Graves' ophthalmopathy (GO). The present study examined the relationship between serum adipocytokine levels and GD and GO. A total of 80 patients with GD participated in this study. The medical records of patients were reviewed retrospectively. GO activity was assessed using the clinical activity score (CAS). GO severity was assessed by the modified NOSPECS classification and included soft tissue involvement, proptosis, and extraocular muscle involvement. Serum adiponectin, leptin, resistin, and retinol-binding protein 4 (RBP-4) levels were measured using commercially available enzyme-linked immunosorbent assays. The prevalence of GO was 36.3%. Serum adiponectin, leptin, and resistin levels were significantly higher in patients with GO than in those without GO. The CAS was positively correlated with serum adiponectin and leptin levels. The total eye score was positively correlated with serum adiponectin, leptin, resistin, and RBP 4 levels. A multivariate analysis revealed that serum leptin and resistin levels were associated with the presence of GO after adjusting for clinical factors. Free thyroxine was negatively correlated with serum leptin level. These results suggest that adipocytokines, such as leptin and resistin, may play a role in inflammatory and autoimmune processes of GD and GO. Future studies with larger numbers of patients are required to establish relationships between serum adipocytokines levels and GO and ascertain the role of adipocytokines in GD and GO. PMID- 26842712 TI - Nucleobindin 2 (NUCB2) in human endometrial carcinoma: a potent prognostic factor associated with cell proliferation and migration. AB - Nucleobindin 2 (NUCB2) is a multifunctional protein containing several functional domains, and associated with wide variety of biological process such as food intake and energy homeostasis. Recently, NUCB2 has been implicated in not only normal human tissues but also some kinds of human malignancies. However, its clinical and/or biological significance has largely remained unknown in endometrial carcinomas. We therefore immunolocalized NUCB2 protein in 87 endometrial carcinoma tissues and examined its clinical significance. NUCB2 immunoreactivity was detected in 19 out of 87 (22%) of endometrial carcinoma cases examined, and positively correlated with Ki67 labeling index, while there was no significant correlation between NUCB2 and stage, histological grade, and progesterone receptor status. Furthermore, NUCB2 immunoreactivity was significantly correlated with increased risk of recurrence and worse clinical outcome regardless of stage or histological grade. Subsequent multivariate analyses did reveal that NUCB2 immunoreactivity was an independent prognostic factor for both disease-free survival and endometrial cancer specific survival. In vitro experiments demonstrated that knockdown of NUCB2 using specific siRNA for NUCB2 significantly impaired cell proliferation and migration of the endometrial carcinoma cell lines, Ishikawa and Sawano cells, and that nesfatin-1 treatment significantly promoted cell proliferation and migration in Ishikawa cells. These findings possibly suggested that NUCB2 and/or nesfatin-1 had pivotal roles in the progression of endometrial carcinomas. Immunohistochemical NUCB2 status may therefore serve as a potent biomarker for endometrial carcinomas. PMID- 26842713 TI - VALIDATION OF A SIMULATION PROCEDURE FOR GENERATING BREAST TOMOSYNTHESIS PROJECTION IMAGES. AB - In order to achieve optimal diagnostic performance in breast tomosynthesis (BT) imaging, the parameters of the imaging chain should be evaluated. For the purpose of such evaluations, a simulation procedure based on the Monte Carlo code system Penelope and the geometry of a Siemens BT system has been developed to generate BT projection images. In this work, the simulation procedure is validated by comparing contrast and sharpness in simulated images with contrast and sharpness in real images acquired with the BT system. The results of the study showed a good agreement of sharpness in real and simulated reconstructed image planes, but the contrast was shown to be higher in the simulated compared with the real projection images. The developed simulation procedure could be used to generate BT images, but it is of interest to further investigate how the procedure could be modified to generate more realistic image noise and contrast. PMID- 26842715 TI - Stereoselective organocatalytic oxidation of alcohols to enals: a homologation method to prepare polyenes. AB - A novel method for organocatalytic oxidation through oxidative enamine catalysis was developed with excellent compatibility for the direct syntheses of enals from simple saturated alcohols. By using this amine-catalyzed IBX-oxidation, a wide range of aromatic and aliphatic substituted enals were successfully generated in high yields and exclusively stereoselective E-geometry. Moreover, varying the solvents and/or the loading amounts of IBX allowed for the selective oxidation of alcohols and aldehydes. Importantly, the homologous application of this method provided a selective and efficient way of preparing various highly sensitive conjugated polyene frameworks, which are enriched in natural products. PMID- 26842714 TI - The well-designed hierarchical structure of Musa basjoo for supercapacitors. AB - Application of biological structure is one of the hottest topics in the field of science and technology. The unimaginable and excellent architectures of living beings supporting their vital activities have attracted the interests of worldwide researchers. An intriguing example is Musa basjoo which belongs to the herb, while appears like a tree. The profound mystery of structure and potential application of Musa basjoo have not been probed. Here we show the finding of the hierarchical structure of Musa basjoo and the outstanding electrochemical performance of the super-capacitors fabricated through the simple carbonization of Musa basjoo followed by KOH activation. Musa basjoo has three layers of structure: nanometer-level, micrometer-level and millimeter-level. The nanometer level structure constructs the micrometer-level structure, while the micrometer level structure constructs the millimeter-level structure. Based on this hierarchical structure, Musa basjoo reduces the unnecessary weight and therefore supports its huge body. The super-capacitors derived from Musa basjoo display a high specific capacitance and a good cycling stability. This enlightening work opens a window for the applications of the natural structure and we hope that more and more people could pay attention to the bio-inspired materials. PMID- 26842717 TI - Bedside Xenon-CT Shows Lower CBF in SAH Patients with Impaired CBF Pressure Autoregulation as Defined by Pressure Reactivity Index (PRx). AB - BACKGROUND: Subarachnoid hemorrhage (SAH) is a disease with a high rate of unfavorable outcome, often related to delayed cerebral ischemia (DCI), i.e., ischemic injury that develops days-weeks after onset, with a multifactorial etiology. Disturbances in cerebral pressure autoregulation, the ability to maintain a steady cerebral blood flow (CBF), despite fluctuations in systemic blood pressure, have been suggested to play a role in the development of DCI. Pressure reactivity index (PRx) is a well-established measure of cerebral pressure autoregulation that has been used to study traumatic brain injury, but not extensively in SAH. OBJECTIVE: To study the relation between PRx and CBF in SAH patients, and to examine if PRx can be used to predict DCI. METHODS: Retrospective analysis of prospectively collected data. PRx was calculated as the correlation coefficient between mean arterial blood pressure (MABP) and intracranial pressure (ICP) in a 5 min moving window. CBF was measured using bedside Xenon-CT (Xe-CT). DCI was diagnosed clinically. RESULTS: 47 poor-grade mechanically ventilated patients were studied. Patients with disturbed pressure autoregulation (high PRx values) had lower CBF, as measured by bedside Xe-CT; both in the early (day 0-3) and late (day 4-14) acute phase of the disease. PRx did not differ significantly between patients who developed DCI or not. CONCLUSION: In mechanically ventilated and sedated SAH patients, high PRx (more disturbed CBF pressure autoregulation) is associated with low CBF, both day 0-3 and day 4-14 after onset. The role of PRx as a monitoring tool in SAH patients needs further studying. PMID- 26842716 TI - A Randomized Trial of Central Venous Catheter Type and Thrombosis in Critically Ill Neurologic Patients. AB - BACKGROUND: Observational studies suggest peripherally inserted central venous catheters (PICCs) are associated with a high risk of catheter-related large vein thrombosis (CRLVT) in critically ill neurologic patients. We evaluated the difference in thrombosis risk between PICCs and centrally inserted central venous catheters (CICVCs). METHODS: We conducted a pragmatic, randomized controlled trial of critically ill adult neurologic patients admitted to neurological and trauma critical care units at two level I trauma centers. Patients were randomized to receive either a PICC or CICVC and undergo active surveillance for CRLVT or death within 15 days of catheter placement. RESULTS: In total, 39 subjects received a PICC and 41 received a CICVC between February 2012 and July 2015. The trial was stopped after enrollment of 80 subjects due to feasibility affected by slow enrollment and funding. In the primary intention-to-treat analysis, 17 (43.6 %) subjects that received a PICC compared to 9 (22.0 %) that received a CICVC experienced the composite of CRLVT or death, with a risk difference of 21.6 % (95 % CI 1.57-41.71 %). Adjusted common odds ratio of CRLVT/death was significantly higher among subjects randomized to receive a PICC (adjusted OR 3.08; 95 % CI 1.1-8.65). The higher adjusted odds ratio was driven by risk of CRLVT, which was higher in those randomized to PICC compared to CICVC (adjusted OR 4.66; 95 % CI 1.3-16.76) due to increased large vein thrombosis without a reduction in proximal deep venous thrombosis. CONCLUSIONS: Our trial demonstrates that critically ill neurologic patients who require a central venous catheter have significantly lower odds of ultrasound-diagnosed CRLVT with placement of a CICVC as compared to a PICC. PMID- 26842719 TI - The SETscore to Predict Tracheostomy Need in Cerebrovascular Neurocritical Care Patients. AB - BACKGROUND AND PURPOSE: Patients with severe stroke who require mechanical ventilation and neurointensive care unit (NICU) management often require a tracheostomy (TT). The optimal time point for TT remains unclear and a controversy in everyday NICU life. Here, we prospectively evaluated a score for prediction of TT need in NICU patients with cerebrovascular disease. METHODS: Seventy-five consecutively ventilated stroke patients were prospectively included in the study and assessed by the stroke-related early tracheostomy score (SETscore) within the first 24 h of admission. Endpoints were TT need, NICU length of stay (NICU-LOS), and ventilation time (VT). We examined the correlation of these variables with the SETscore using regression analysis and determined a cut-off by receiver operating characteristic (ROC) analysis. RESULTS: Twenty-six patients had to be tracheostomized. The mean VT was 8.7 +/-8 days and the mean NICU-LOS was 11.6 +/- 8 days. The SETscore predicted NICU-LOS with a positive predictive value of 0.748 (p < 0.001) and VT with a positive predictive value of 0.799 (p < 0.001). The ROC analysis demonstrated a SETscore value of 8 to be the optimal cut-off to predict prolonged NICU-LOS, VT, and TT need with a sensitivity of 64 % and a specificity of 86 %. CONCLUSIONS: Based on this monocentric study, the SETscore seems to be a valid tool to indicate prolonged NICU-LOS and VT, as well as TT need in cerebrovascular NICU patients. Confirmation of these results in larger cohorts with various settings may help to develop the SETscore as a decisive tool on primary TT early in time to avoid extubation failure. PMID- 26842718 TI - Hypernatremia at Hospital Discharge and Out of Hospital Mortality Following Primary Intracerebral Hemorrhage. AB - BACKGROUND AND PURPOSE: In patients with intracerebral hemorrhage (ICH), it is not clear if hypernatremia is merely a marker of disease severity or if elevated sodium levels are harmful. We hypothesized that hypernatremia at hospital discharge in primary ICH patients would be associated with increased mortality following discharge. METHODS: We performed a two-center observational study of critically ill ICH patients in Boston. We studied 5100 patients, age >=18 years, who were diagnosed with ICH (ICD-9 code 431), received medical or surgical critical care between 1997 and 2011 and survived hospitalization. The exposure of interest was serum sodium within 24 h of hospital discharge, categorized as Na <= 145 mmol/L and Na > 145 mmol/L. The primary outcome was 30-day post-discharge mortality. Odds ratios were estimated by logistic regression models adjusted for age, race, gender, Deyo-Charlson Index, patient type (medical versus surgical) and sepsis. RESULTS: In ICH patients who received critical care and survived hospitalization, the serum sodium at discharge was a predictor of post-discharge mortality. Patients with a discharge Na > 145 mmol/L have an OR for mortality in the 30 days following hospital discharge of 1.82 (95 %CI 1.38-2.38; P < 0.001) and an adjusted OR of 1.87 (95 %CI 1.40-2.48; P < 0.001) both relative to patients with a discharge Na <= 145 mmol/L. The adjusted model showed good discrimination AUC 0.77 (95 %CI 0.74-0.79) and calibration (Hosmer-Lemeshow chi (2) P = 0.68). CONCLUSIONS: In critically ill ICH patients who survive hospitalization, hypernatremia at the time of discharge is a robust predictor of post-discharge mortality. PMID- 26842720 TI - "It gives them more options": preferences for preconception genetic carrier screening for fragile X syndrome in primary healthcare. AB - This study aims to explore stakeholder views about offering population-based genetic carrier screening for fragile X syndrome. A qualitative study using interviews and focus groups with stakeholders was undertaken to allow for an in depth exploration of views and perceptions about practicalities of, and strategies for, offering carrier screening for fragile X syndrome to the general population in healthcare settings. A total of 188 stakeholders took part including healthcare providers (n = 81), relatives of people with fragile X syndrome (n = 29), and members of the general community (n = 78). The importance of raising community awareness about screening and providing appropriate support for carriers was emphasized. There was a preference for preconception carrier screening and for providing people with the opportunity to make an informed decision about screening. Primary care was highlighted as a setting which would ensure screening is accessible; however, challenges of offering screening in primary care were identified including time to discuss screening, knowledge about the test and possible outcomes, and the health professionals' approach to offering screening. With the increasing availability of genetic carrier tests, it is essential that research now focuses on evaluating approaches for the delivery of carrier screening programs. Primary healthcare is perceived as an appropriate setting through which to access the target population, and raising awareness is essential to making genetic screening more accessible to the general community. PMID- 26842721 TI - Health research: working with Indigenous People in Peru. PMID- 26842722 TI - Molecular cloning of a coiled-coil-nucleotide-binding-site-leucine-rich repeat gene from pearl millet and its expression pattern in response to the downy mildew pathogen. AB - Downy mildew caused by Sclerospora graminicola is a devastating disease of pearl millet. Based on candidate gene approach, a set of 22 resistance gene analogues were identified. The clone RGPM 301 (AY117410) containing a partial sequence shared 83% similarity to rice R-proteins. A full-length R-gene RGA RGPM 301 of 3552 bp with 2979 bp open reading frame encoding 992 amino acids was isolated by the degenerate primers and rapid amplification of cDNA ends polymerase chain reaction (RACE-PCR) approach. It had a molecular mass of 113.96 kDa and isoelectric point (pI) of 8.71. The sequence alignment and phylogenetic analysis grouped it to a non-TIR NBS LRR group. The quantitative real-time PCR (qRT-PCR) analysis revealed higher accumulation of the transcripts following inoculation with S. graminicola in the resistant cultivar (IP18296) compared to susceptible cultivar (7042S). Further, significant induction in the transcript levels were observed when treated with abiotic elicitor beta-aminobutyric acid (BABA) and biotic elicitor Pseudomonas fluorescens. Exogenous application of phytohormones jasmonic acid or salicylic acid also up-regulated the expression levels of RGA RGPM 301. The treatment of cultivar IP18296 with mitogen-activated protein kinase (MPK) inhibitors (PD98059 and U0126) suppressed the levels of RGA RGPM 301. A 3.5 kb RGA RGPM 301 which is a non-TIR NBS-LRR protein was isolated from pearl millet and its up-regulation during downy mildew interaction was demonstrated by qRT PCR. These studies indicate a role for this RGA in pearl millet downy mildew interaction. PMID- 26842723 TI - Stereotactic Body Radiotherapy (SBRT) with Lower Doses for Selected Patients with Stage I Non-small-cell Lung Cancer (NSCLC). AB - SBRT is very effective for stage I NSCLC. Biologically effective doses (BED) >100 Gy are recommended. Elderly patients and those with a limited performance status may not tolerate these high doses. This study investigated the outcomes after lower dose SBRT (BED < 90 Gy) in 46 patients with stage I NSCLC, who were aged >=70 years or in reduced general condition. Local control rates at 1, 2, and 3 years were 100, 95, and 95 %, respectively. Rates of freedom from distant progression were 83, 63, and 54 %, and survival rates were 77, 57, and 36 %, respectively. Seventeen patients died during the follow-up, 11 (65 %) from distant progression of NSCLC, and six (35 %) from non-malignant causes. No patient developed radiation-induced pneumonitis. Thus, SBRT with BED <90 Gy resulted in excellent local control and appears to be a reasonable option for stage I NSCLC in elderly patients and those with a poor performance status. PMID- 26842724 TI - Three-Dimensional Gene Map of Cancer Cell Types: Structural Entropy Minimisation Principle for Defining Tumour Subtypes. AB - In this study, we propose a method for constructing cell sample networks from gene expression profiles, and a structural entropy minimisation principle for detecting natural structure of networks and for identifying cancer cell subtypes. Our method establishes a three-dimensional gene map of cancer cell types and subtypes. The identified subtypes are defined by a unique gene expression pattern, and a three-dimensional gene map is established by defining the unique gene expression pattern for each identified subtype for cancers, including acute leukaemia, lymphoma, multi-tissue, lung cancer and healthy tissue. Our three dimensional gene map demonstrates that a true tumour type may be divided into subtypes, each defined by a unique gene expression pattern. Clinical data analyses demonstrate that most cell samples of an identified subtype share similar survival times, survival indicators and International Prognostic Index (IPI) scores and indicate that distinct subtypes identified by our algorithms exhibit different overall survival times, survival ratios and IPI scores. Our three-dimensional gene map establishes a high-definition, one-to-one map between the biologically and medically meaningful tumour subtypes and the gene expression patterns, and identifies remarkable cells that form singleton submodules. PMID- 26842725 TI - Private tuberculosis testing is cheaper in India. PMID- 26842726 TI - Genetic diversity and conservation status of managed vicuna (Vicugna vicugna) populations in Argentina. AB - The vicuna (Vicugna vicugna) was indiscriminately hunted for more than 400 years and, by the end of 1960s, it was seriously endangered. At that time, a captive breeding program was initiated in Argentina by the National Institute of Agricultural Technology (INTA) with the aim of preserving the species. Nowadays, vicunas are managed in captivity and in the wild to obtain their valuable fiber. The current genetic status of Argentinean vicuna populations is virtually unknown. Using mitochondrial DNA and microsatellite markers, we assessed levels of genetic diversity of vicuna populations managed in the wild and compared it with a captive population from INTA. Furthermore, we examined levels of genetic structure and evidence for historical bottlenecks. Overall, all populations revealed high genetic variability with no signs of inbreeding. Levels of genetic diversity between captive and wild populations were not significantly different, although the captive population showed the lowest estimates of allelic richness, number of mitochondrial haplotypes, and haplotype diversity. Significant genetic differentiation at microsatellite markers was found between free-living populations from Jujuy and Catamarca provinces. Moreover, microsatellite data also revealed genetic structure within the Catamarca management area. Genetic signatures of past bottlenecks were detected in wild populations by the Garza Williamson test. Results from this study are discussed in relation to the conservation and management of the species. PMID- 26842727 TI - Comprehensive study on critical micellar concentrations of SDS in acetonitrile water solvents. AB - The CMC is one of the fundamental characteristics of surfactants and its determination is crucial for detail understanding of micelles formation. In this study the CMC of SDS in presence of ACN was determined by two independent experimental techniques, capillary electrophoresis and fluorescence correlation spectroscopy (FCS). Yet, studies of SDS micellization in solutions containing ACN as organic modifier are sparse and inconsistent in literature. The measurements were performed for various ACN contents in the range of 0-50% v/v. At ACN contents of up to 10% v/v the CMC is lower when compared to the aqueous solution, while increasing ACN content causes a significant increase of the CMC. Formation of micelles was observed up to ACN concentrations of 35% v/v, which is in contrast to most of the reports in literature. Based on the results of the FCS experiments, we were able to confirm that presence of ACN causes a gradual increase of the size of the micelles with increasing concentration of SDS. Simultaneously, we proved that the classical conductivity approach for the determination of the CMC does not yield reliable results in the presence of higher content of an organic modifier such as ACN. PMID- 26842730 TI - Neglect and hereditary risk: Their relative contribution to schizophrenia with negative symptomatology. AB - BACKGROUND: There is evidence that genetic and environmental stressors contribute to the genesis of schizophrenia. However, the relevant impact of each factor remains unclear. We tested for an interactive effect between childhood neglect and family history of serious mental illness. Data were further analyzed for a possible connection to type of schizophrenic symptoms. SAMPLING/METHODS: Data for the study are taken from the medical records of 641 patients with schizophrenia from a large state hospital in the northeastern United States. Clinical assessments were divided into positive and negative symptomatology through application of the Scale for the Assessment of Negative Symptoms (SANS), the Scale for the Assessment of Positive Symptoms (SAPS) and the Positive and Negative Syndrome Scale (PANSS). Detailed information about childhood neglect and family history of serious mental illness was obtained through Social Service Assessment interviews at intake and during hospital stay. RESULTS: Among clients with no family history of mental illness, childhood neglect does not meaningfully affect the risk of negative versus positive schizophrenia. For clients with such history, on the other hand, neglect significantly raises the risk of schizophrenia with negative symptomatology. CONCLUSION: Our central finding is that risk for negative symptoms of schizophrenia are elevated by childhood neglect combined with a history of serious mental illness within the family. This is the only report to combine schizophrenic symptoms, familial risk and childhood neglect to date. Implications for primary prevention and treatment are discussed. PMID- 26842728 TI - Choice of antiretroviral drugs for continued treatment scale-up in a public health approach: what more do we need to know? AB - INTRODUCTION: There have been several important developments in antiretroviral treatment in the past two years. Randomized clinical trials have been conducted to evaluate a lower dose of efavirenz (400 mg once daily). Integrase inhibitors such as dolutegravir have been approved for first-line treatment. A new formulation of tenofovir (alafenamide) has been developed and has shown equivalent efficacy to tenofovir in randomized trials. Two-drug combination treatments have been evaluated in treatment-naive and -experienced patients. The novel pharmacokinetic booster cobicistat has been compared to ritonavir in terms of pharmacokinetics, efficacy and safety. The objective of this commentary is to assess recent developments in antiretroviral drug treatment to determine whether new treatments should be included in new international guidelines. DISCUSSION: The use of first-line treatment with tenofovir and efavirenz at the standard 600 mg once-daily dose should remain the first-choice standard of care treatment. Evidence supporting a switch to efavirenz 400 mg once daily or integrase inhibitors is sufficient to consider these drugs as alternative first-line options, but more data are needed on their use in pregnant women and people with TB co-infection. The use of new formulations of tenofovir is currently too preliminary to justify immediate adoption and scale-up across HIV programmes in low- and middle-income countries. The evidence supporting use of two-drug combinations is not considered strong enough to justify changed recommendations from use of standard triple drug combinations. Cobicistat does not offer significant safety advantages over ritonavir as a pharmacokinetic booster. CONCLUSIONS: For continued scale-up of antiretroviral treatment in low- and middle-income countries, use of first-line triple combinations including efavirenz 600 mg once daily is supported by the largest evidence base. Additional studies are underway to evaluate new treatments in key populations, and these results may justify changes to these recommendations. PMID- 26842729 TI - ABCC4 Is a Determinant of Cytarabine-Induced Cytotoxicity and Myelosuppression. AB - Resistance to cytarabine remains a major challenge in the treatment of acute myeloid leukemia (AML). Based on previous studies implicating ABCC4/MRP4 in the transport of nucleosides, we hypothesized that cytarabine is sensitive to ABCC4 mediated efflux, thereby decreasing its cytotoxic response against AML blasts. The uptake of cytarabine and its monophosphate metabolite was found to be facilitated in ABCC4-expressing vesicles and intracellular retention was significantly impaired by overexpression of human ABCC4 or mouse Abcc4 (P < 0.05). ABCC4 was expressed highly in AML primary blasts and cell lines, and cytotoxicity of cytarabine in cells was increased in the presence of the ABCC4 inhibitors MK571 or sorafenib, as well as after ABCC4 siRNA. In Abcc4-null mice, cytarabine-induced hematological toxicity was enhanced and ex vivo colony-forming assays showed that Abcc4-deficiency sensitized myeloid progenitors to cytarabine. Collectively, these studies demonstrate that ABCC4 plays a protective role against cytarabine-mediated insults in leukemic and host myeloid cells. PMID- 26842731 TI - Temperature-modulated graphene oxide resistive humidity sensor for indoor air quality monitoring. AB - In this paper we present a temperature-modulated graphene oxide (GO) resistive humidity sensor that employs complementary-metal-oxide-semiconductor (CMOS) micro electro-mechanical-system (MEMS) micro-hotplate technology for the monitoring and control of indoor air quality (IAQ). GO powder is obtained by chemical exfoliation, dispersed in water and deposited via ink-jet printing onto a low power micro-hotplate. Atomic force microscopy (AFM) and transmission electron microscopy (TEM) show the typical layered and wrinkled morphology of the GO. Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and Fourier transform infra-red (FTIR) spectroscopy indicate that the GO flakes possess a significant number of oxygen containing functional groups (epoxy, carbonyl, hydroxyl) extremely attractive for humidity detection. Electro-thermal characterisation of the micro-hotplates shows a thermal efficiency of 0.11 mW per degrees C, resulting in a sensor DC power consumption of only 2.75 mW at 50 degrees C. When operated in an isothermal mode, the sensor response is detrimentally affected by significant drift, hysteretic behaviour, slow response/recovery times and hence poor RH level discrimination. Conversely, a temperature modulation technique coupled with a differential readout methodology results in a significant reduction of the sensor drift, improved linear response with a sensitivity of 0.14 mV per %, resolution below 5%, and a maximum hysteresis of +/-5%; response and recovery times equal to 189 +/- 49 s and 89 +/- 5 s, respectively. These performance parameters satisfy current IAQ monitoring requirements. We have thus demonstrated the effectiveness of integrating GO on a micro-hotplate CMOS compatible platform enabling temperature modulation schemes to be easily applied in order to achieve compact, low power, low cost humidity IAQ monitoring. PMID- 26842732 TI - Multi-country comparison of delivery strategies for mass campaigns to achieve universal coverage with insecticide-treated nets: what works best? AB - BACKGROUND: The use of insecticide-treated nets (ITNs) is widely recognized as one of the main interventions to prevent malaria. High ITN coverage is needed to reduce transmission. Mass distribution campaigns are the fastest way to rapidly scale up ITN coverage. However, the best strategy to distribute ITNs to ensure household coverage targets are met is still under debate. This paper presents results from 14 post-campaign surveys in five African countries to assess whether the campaign strategy used had any effect on distribution outcome. METHODS: Data from 13,901 households and 14 campaigns from Ghana, Nigeria, Senegal, South Sudan and Uganda, were obtained through representative cross-sectional questionnaire surveys, conducted three to 16 months after ITN distribution. All evaluations used a multi-stage sampling approach and similar methods for data collection. Key outcomes examined were the proportion of households having received a net from the campaign and the proportion of households with one net for every two people. RESULTS: Household registration rates proved to be the most important determinant of a household receiving any net from the campaign (adjusted odds ratio [OR] 74.8; 95 % confidence interval [CI]: 55.3-101.1) or had enough ITNs for all household members (adjusted OR 19.1; 95 % CI: 55.34-101.05). Factors that positively influenced registration were larger household size (adjusted OR 1.7; 95 % CI: 1.5-2.1) and families with children under five (adjusted OR 1.4; 95 % CI: 1.2-1.6). Urban residence was negatively associated with receipt of a net from the campaign (adjusted OR 0.73; 95 % CI: 0.58-0.92). Registration was equitable in most campaigns except for Uganda and South Sudan, where the poorest wealth quintiles were less likely to have been reached. After adjusting for other factors, delivery strategy (house-to-house vs. fixed point) and distribution approach (integrated versus stand-alone) did not show a systematic impact on registration or owning any ITN. Campaigns that used a universal coverage allocation strategy were more effective in increasing the proportion of households with enough ITNs than campaigns that used a fixed number of ITNs. Registering based on counting usual sleeping spaces resulted in higher levels of households with one net per two people among those receiving any campaign net (adjusted OR 1.6; 95 % CI: 1.07-2.48) than campaigns that registered based on the number of household members. CONCLUSION: All of the campaigns, irrespective of strategy, successfully increased ownership of at least one ITN. Delivery method and distribution approach were not associated with receipt of at least one ITN from the campaign. Rather, the key determining factor for receipt of at least one ITN from the campaign was a successful registration process, which depends on the ability of community volunteers to reach households during the exercise. Universal coverage campaigns, especially those that used a sleeping space allocation strategy, were more effective in increasing the proportion of households with enough ITNs. Maximizing registration completeness and using a universal coverage allocation strategy are therefore likely to improve campaign outcomes. PMID- 26842734 TI - Stay cool or in good contact? PMID- 26842733 TI - Identification of Microalgae by Laser Desorption/Ionization Mass Spectrometry Coupled with Multiple Nanomatrices. AB - In this study, we demonstrate a simple method to identify microalgae by surface assisted laser desorption/ionization mass spectrometry (SALDI-MS) using three different substrates: HgSe, HgTe, and HgTeSe nanostructures. The fragmentation/ionization processes of complex molecules in algae varied according to the heat absorption and transfer efficiency of the nanostructured matrices (NMs). Therefore, the mass spectra obtained for microalgae showed different patterns of m/z values for different NMs. The spectra contained both significant and nonsignificant peaks. Constructing a Venn diagram with the significant peaks obtained for algae when using HgSe, HgTe, and HgTeSe NMs in m/z ratio range 100 1000, a unique relationship among the three sets of values was obtained. This unique relationship of sets is different for each species of microalgae. Therefore, by observing the particular relationship of sets, we successfully identified different algae such as Isochrysis galbana, Emiliania huxleyi, Thalassiosira weissflogii, Nannochloris sp., Skeletonema cf. costatum, and Tetraselmis chui. This simple and cost-effective SALDI-MS analysis method coupled with multi-nanomaterials as substrates may be extended to identify other microalgae and microorganisms in real samples. Graphical Abstract Identification of microalgae by surface-assisted laser desorption/ionization mass spectrometry coupled with three different mercury-based nanosubstrates. PMID- 26842736 TI - Correction to "The Impact of Single Nucleotide Polymorphisms on Human Aldehyde Oxidase". PMID- 26842735 TI - The use of wearable cardioverter-defibrillators in Europe: results of the European Heart Rhythm Association survey. AB - The aim of this European Heart Rhythm Association (EHRA) survey was to collect data on the use of wearable cardioverter-defibrillators (WCDs) among members of the EHRA electrophysiology research network. Of the 50 responding centres, 23 (47%) reported WCD use. Devices were fully reimbursed in 17 (43.6%) of 39 respondents, and partially reimbursed in 3 centres (7.7%). Eleven out of 20 centres (55%) reported acceptable patients' compliance (WCD worn for >90% of time). The most common indications for WCD (8 out of 10 centres; 80%) were covering the period until re-implantation of ICD explanted due to infection, in patients with left ventricular impairment due to myocarditis or recent myocardial infarction and those awaiting heart transplantation. Patient life expectancy of <12 months and poor compliance were the most commonly reported contraindications for WCD (24 of 46 centres, 52.2%). The major problems encountered by physicians managing patients with WCD were costs (8 of 18 centres, 44.4%), non-compliance, and incorrect use of WCD. Four of 17 centres (23.5%) reported inappropriate WCD activations in <5% of patients. The first shock success rate in terminating ventricular arrhythmias was 95-100% in 6 of 15 centres (40%), 85-95% in 4 (26.7%), 75-85% in 2 (13.3%), and <75% in 3 centres (20%). The survey has shown that the use of WCD in Europe is still restricted and depends on reimbursement. Patients' compliance remains low. Heterogeneity of indications for WCD among centres underscores the need for further research and a better definition of indications for WCD in specific patient groups. PMID- 26842737 TI - Label-free Electrochemiluminescent Immunosensor for Detection of Prostate Specific Antigen based on Aminated Graphene Quantum Dots and Carboxyl Graphene Quantum Dots. AB - Prostate-specific antigen (PSA) was used as the model, an ultrasensitive label free electrochemiluminescent immunosensor was developed based on graphene quantum dots. Au/Ag-rGO was sythsized and used as electrode material to load a great deal of graphene quantum dots due to the large surface area and excellent electron conductivity. After aminated graphene quantum dots and acarboxyl graphene quantum dots were modified onto the electrode, the ECL intensity was much high using K2S2O8 as coreactant. Then, antibody of PSA was immobilized on the surface of modified electrode surface through the adsorption of Au/Ag toward proteins, leading to the decrease of the ECL intensity. As proven by ECL spectra test and electrochemical impedance spectroscopy (EIS) analysis, the fabrication process of the immunosensor is successful. Under the optimal conditions, the ECL intensity decreased linearly with the logarithm of PSA concentration in the range of 1 pg/mL ~ 10 ng/mL. The detection limit achieved is 0.29 pg/mL. The immunosensor results were validated through the detection of PSA in serum samples with satisfactory results. Due to excellent stability, high sensitivity, acceptable repeatability and selectivity, the immunosensor has promising applications in disease and drug analysis. PMID- 26842738 TI - Reply to the Letter to the Editor by Murru et al. PMID- 26842739 TI - Transfer hydrogenation with abnormal dicarbene rhodium(iii) complexes containing ancillary and modular poly-pyridine ligands. AB - Treatment of an abnormal dicarbene ligated rhodium(iii) dimer with 2,2' bipyridine (bipy), 1,10-phenanthroline (phen) or 2,2':6',2''-terpyridine (terpy) results in coordination of the N-donor ligands and concomitant cleavage of the dimeric structure. Depending on the denticity of the pyridyl ligand, this situation retains one (L = terpy) or two (L = bipy, phen) flexible sites for substrate coordination. In the case of the bipy complexes, modification of the electron density at Rh, without directly affecting the steric environment about the metal centre, was achieved by the incorporation of electron-donating or electron-withdrawing substituents on the bipy backbone. The dicarbene pyridyl complexes were active in transfer hydrogenation catalysis of benzophenone at 0.15 mol% catalyst loading in a iPrOH/KOH mixture. The catalysts displayed a strong characteristic colour change (yellow to purple) after activation which allowed for visual monitoring of the status of the reaction. The colour probe and the robustness of the active catalysts proved useful for catalyst recycling. The catalytic activity sustained over five consecutive substrate batch additions and gave a maximum overall turnover number of 3100. PMID- 26842740 TI - John Hunter and the origin of the term "angiogenesis". PMID- 26842741 TI - Hyperglycemia Increases the Production of Amyloid Beta-Peptide Leading to Decreased Endothelial Tight Junction. AB - AIMS: Amyloid beta-peptide (Abeta), the main component of senile plaques in the Alzheimer's disease (AD) brains, is generated from sequential cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase. Hyperglycemia in diabetes may compromise barrier integrity in endothelial cells (ECs). However, the roles of endothelial APP in response to high glucose (HG) remain to be delineated. The aims of this study were to test whether HG may increase Abeta secretion, thereby leading to heightened paracellular permeability in ECs. METHODS: We determined the effects of HG on production of Abeta, expression of full-length APP, intercellular permeability, and expression levels of specific junctional proteins in human umbilical vein endothelial cells (HUVECs). RESULTS: HG at 30 mM significantly stimulated expression of full-length APP accompanied by heightened secretion of Abeta1-42, increased paracellular permeability, and attenuated expression of zona occluden-1 (ZO-1), claudin-5, occludin, and junctional adhesion molecule (JAM)-C in HUVECs; all of which were abolished by the gamma secretase inhibitor BMS299897. Exogenous application of Abeta1-42, but not the reverse peptide Abeta42-1, was sufficient to downregulate the expression of the same junction proteins. CONCLUSION: Hyperglycemia enhances APP expression with increased Abeta production, which downregulates junctional proteins causing increased intercellular permeability in ECs. PMID- 26842742 TI - The exceptional genomic word symmetry along DNA sequences. AB - BACKGROUND: The second Chargaff's parity rule and its extensions are recognized as universal phenomena in DNA sequences. However, parity of the frequencies of reverse complementary oligonucleotides could be a mere consequence of the single nucleotide parity rule, if nucleotide independence is assumed. Exceptional symmetry (symmetry beyond that expected under an independent nucleotide assumption) was proposed previously as a meaningful measure of the extension of the second parity rule to oligonucleotides. The global exceptional symmetry was detected in long and short genomes. RESULTS: To explore the exceptional genomic word symmetry along the genome sequences, we propose a sliding window method to extract the values of exceptional symmetry (for all words or by word groups). We compare the exceptional symmetry effect size distribution in all human chromosomes against control scenarios (positive and negative controls), testing the differences and performing a residual analysis. We explore local exceptional symmetry in equivalent composition word groups, and find that the behaviour of the local exceptional symmetry depends on the word group. CONCLUSIONS: We conclude that the exceptional symmetry is a local phenomenon in genome sequences, with distinct characteristics along the sequence of each chromosome. The local exceptional symmetry along the genomic sequences shows outlying segments, and those segments have high biological annotation density. PMID- 26842743 TI - Genetic links between bacterial dynamin and flotillin proteins. AB - Dynamin is a membrane-associated GTPase that confers motor-like functions in membrane dynamics, such as endocytosis, in eukaryotic cells. Flotillin (reggie) proteins are also a widely conserved class of membrane proteins, associated with the formation of protein assemblies within the membrane, and with endocytotic processes. Bacterial dynamin has been shown to bind to membranes in vitro and to mediate membrane fusion. Bacillus subtilis DynA localizes to the cell division septum, and it was recently shown that it indeed plays a role in cell division. Interestingly, dynamin shows a genetic interaction with flotillin proteins in this prokaryotic model organism and the absence of both proteins results in a cell division and cell shape defect. Here, we show that in addition to the morphological phenotypes, a dynamin/flotillin double deletion strain shows a synthetic defect in cell motility, much stronger than that of flotillin single mutant cells. While the contribution of altered cell shape and slower growth of the double deletion strain on motility cannot be clearly assessed, our data emphasize the fact that dynamin and flotillin proteins play tightly connected functions in a wide range of aspects in membrane processes in bacteria. PMID- 26842744 TI - In defence of utility: the medical humanities and medical education. AB - The idea that a study of the humanities helps to humanise doctors has become a leitmotif within the field. It is argued that the humanities (especially, literature) help to foster insights beyond those provided by biomedical training. Healthy young medics, it is claimed, can thereby gain significant insights into patienthood, and obtain important skills that may be valuable for their professional life. But the instrumentality of the humanities is not the only justification proffered for its inclusion in medical curricula. In this paper I critically examine the two overarching justifications recurrently cited in the mainstream literature-namely, (1) the instrumental worth and (2) the intrinsic value of the medical humanities in educating doctors. Examining these theses (and focusing on the views of a leading medical humanities scholar) I show that the bifurcation into instrumental versus non-instrumental justifications is not supported by the argumentation. Instead, I find that the particulars of the supposedly intrinsic justifications amount to an unambiguously instrumental defence of the humanities. Contextualizing the present investigation to probe further, I describe a long history of debate about the role of the humanities in British education and find that it rests on unsupported dichotomies (utility vs non-utility, theoretical vs applied, educated vs trained). I conclude that the medical humanities' manifesto would be more intellectually honest and coherent, and provide a more robust defence of its value in medical education, if it chose to embrace a wholly instrumental rationale for its role. PMID- 26842745 TI - Magnetic. PMID- 26842746 TI - Fluorescent molecularly imprinted polymer based on Navicula sp. frustules for optical detection of lysozyme. AB - The direct correlation between disease and lysozyme (LYZ) levels in human body fluids makes the sensitive and convenient detection of LYZ the focus of scientific research. Fluorescent molecularly imprinted polymer has emerged as a new alternative for LYZ detection in order to resolve the limitation of immunoassays, which are expensive, unstable, require complex preparation, and are time consuming. In this study, a novel fluorescence molecularly imprinted polymer based on Navicula sp. frustules (FITC-MIP) has been synthesized via post imprinting treatment for LYZ detection. Navicula sp. frustules were used as supported material because of their unique properties of moderate surface area, reproducibility, and biocompatibility, to address the drawbacks of nanoparticle core material with low adsorption capacity. The FITC acts as recognition signal and optical readout, whereas MIP provides LYZ selectivity. The synthesized FITC MIP showed a response time as short as 5 min depending on the concentration of LYZ. It is found that the LYZ template can significantly quench the fluorescence intensity of FITC-MIP linearly within a concentration range of 0 to 0.025 mg mL( 1), which is well described by Stern-Volmer equation. The FITC-MIP can selectively and sensitively detect down to 0.0015 mg mL(-1) of LYZ concentration. The excellent sensing performance of FITC-MIP suggests that FITC-MIP is a potential biosensor in clinical diagnosis applications. PMID- 26842747 TI - Analysis of tetrahydroxylated benzo[a]pyrene isomers in hair as biomarkers of exposure to benzo[a]pyrene. AB - A first gas chromatography-tandem mass spectrometry (GC-MS/MS) method was designed for analysis of four tetrahydroxylated benzo[a]pyrene metabolites (benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, benzo[a]pyrene-r-7,t-8,t-9,t 10-tetrahydrotetrol, benzo[a]pyrene-r-7,t-8,c-9,c-10-tetrahydrotetrol, and benzo[a]pyrene-r-7,t-8,c-9,t-10-tetrahydrotetrol) in hair. Hair powder extract was submitted to liquid-solid extraction, followed by C18 solid-phase purification. The analytes were derivatized with use of N-methyl-N (trimethylsilyl)trifluoroacetamide and then analyzed by GC-MS/MS in negative chemical ionization mode. The calibration curve was linear from the limit of quantification (LOQ) to 20 pg/mg in hair. The coefficient of determination of the calibration curve was more than 0.975 for all the analytes investigated. The LOQs ranged from 0.075 to 0.2 pg/mg in hair. The method was afterward applied to the analysis of hair of 16 rats randomly allocated to experimental groups receiving 16 polycyclic aromatic hydrocarbons solubilized in oil at 0 or 0.8 mg/kg body weight by oral administration three times per week for 90 days. The analysis of monohydroxylated and dihydroxylated benzo[a]pyrenes was conducted in parallel by GC-MS/MS on the same samples. All tetrahydroxylated benzo[a]pyrene isomers were detected in hair samples collected from rats exposed to polycyclic aromatic hydrocarbons. Benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydrotetrol, the most abundant isomer in hair of treated rats, was also the principal isomer released in DNA adduct hydrolysis in humans. Moreover, the benzo[a]pyrene-r-7,t-8,t-9,c-10 tetrahydrotetrol concentrations in hair were significantly greater than those of 2-hydroxybenzo[a]pyrene, 1-hydroxybenzo[a]pyrene, 7-hydroxybenzo[a]pyrene, and 4 hydroxybenzo[a]pyrene and similar to those of 9-hydroxybenzo[a]pyrene and 3 hydroxybenzo[a]pyrene. The method was also sufficiently sensitive to monitor environmental levels of exposure because two hair specimens in the eight analyzed from smokers were above the LOQ for benzo[a]pyrene-r-7,t-8,t-9,c-10 tetrahydrotetrol and benzo[a]pyrene-r-7,t-8,c-9,t-10-tetrahydrotetrol. This study therefore demonstrated that tetrahydroxylated benzo[a]pyrenes in hair might be a useful biomarker for the assessment of both the general population and occupationally exposed workers. PMID- 26842748 TI - Nucleotide-dependent assembly of the peroxisomal receptor export complex. AB - Pex1p and Pex6p are two AAA-ATPases required for biogenesis of peroxisomes. Both proteins form a hetero-hexameric complex in an ATP-dependent manner, which has a dual localization in the cytosol and at the peroxisomal membrane. At the peroxisomal membrane, the complex is responsible for the release of the import receptor Pex5p at the end of the matrix protein import cycle. In this study, we analyzed the recruitment of the AAA-complex to its anchor protein Pex15p at the peroxisomal membrane. We show that the AAA-complex is properly assembled even under ADP-conditions and is able to bind efficiently to Pex15p in vivo. We reconstituted binding of the Pex1/6p-complex to Pex15p in vitro and show that Pex6p mediates binding to the cytosolic part of Pex15p via a direct interaction. Analysis of the isolated complex revealed a stoichiometry of Pex1p/Pex6p/Pex15p of 3:3:3, indicating that each Pex6p molecule of the AAA-complex binds Pex15p. Binding of the AAA-complex to Pex15p in particular and to the import machinery in general is stabilized when ATP is bound to the second AAA-domain of Pex6p and its hydrolysis is prevented. The data indicate that receptor release in peroxisomal protein import is associated with a nucleotide-depending Pex1/6p-cycle of Pex15p binding and release. PMID- 26842749 TI - Prevalence and clinical characteristics of psoriasis in spondyloarthritis: a descriptive analysis of 275 patients. AB - OBJECTIVES: To assess the prevalence of psoriasis among a cohort of patients with spondyloarthritis (SpA), to describe the clinical characteristics of psoriasis and associations with other manifestations. METHODS: This is a retrospective single-centre observational study. The patients were diagnosed with definite SpA (expert opinion), either axial or peripheral. Each patient underwent a direct interview by a physician. The data regarding history of psoriasis and its clinical characteristics were collected. Univariate and multivariate analyses of patients with versus without psoriasis were carried out. RESULTS: In all, 275 SpA patients were assessed: mean disease duration 16.7+/-11.8 years, 61.4% were men, 69.1% were diagnosed as axial SpA and 17.8% as peripheral SpA. In all, 84 patients (30.5%) had present or past psoriasis. The prevalence of psoriasis was high whatever the clinical presentation. Psoriasis was present before or concomitantly to diagnosis of SpA in 59/84 patients (70.2%). The most common types of psoriasis were plaque (66.7% of patients with psoriasis) and scalp psoriasis (65.5%). Other localisations were not rare, including palmoplantar pustulosis (20.2%) or nail psoriasis (19.1%). Patients with versus without psoriasis differed only through a lower proportion of radiological sacroiliitis (57.5% vs. 81.3 %, p<0.001). CONCLUSIONS: With a prevalence of 30.5%, i.e. ten times higher than in the general population, this study confirms that psoriasis is a frequent and early manifestation in SpA and that a systematic search for psoriasis (e.g. scalp) is relevant in SpA for clinical practice, whatever the clinical presentation of SpA. PMID- 26842750 TI - Using Quantitative Seroproteomics to Identify Antibody Biomarkers in Pancreatic Cancer. AB - Pancreatic cancer is the fourth leading cause of cancer-related deaths in the United States. Less than 6% of patients survive beyond the fifth year due to inadequate early diagnostics and ineffective treatment options. Our laboratory has developed an allogeneic, granulocyte-macrophage colony-stimulating factor (GM CSF)-secreting pancreatic cancer vaccine (GVAX) that has been tested in phase II clinical trials. Here, we employed a serum antibodies-based SILAC immunoprecipitation (SASI) approach to identify proteins that elicit an antibody response after vaccination. The SASI approach uses immunoprecipitation with patient-derived antibodies that is coupled to quantitative stable isotope-labeled amino acids in cell culture (SILAC). Using mass spectrometric analysis, we identified more than 150 different proteins that induce an antibody response after vaccination. The regulatory subunit 12A of protein phosphatase 1 (MYPT1 or PPP1R12A), regulatory subunit 8 of the 26S proteasome (PSMC5), and the transferrin receptor (TFRC) were shown to be pancreatic cancer-associated antigens recognized by postvaccination antibodies in the sera of patients with favorable disease-free survival after GVAX therapy. We further interrogated these proteins in over 80 GVAX-treated patients' pancreases and uniformly found a significant increase in the expression of MYPT1, PSMC5, and TFRC in neoplastic compared with non-neoplastic pancreatic ductal epithelium. We show that the novel SASI approach can identify antibody targets specifically expressed in patients with improved disease-free survival after cancer vaccine therapy. These targets need further validation to be considered as possible pancreatic cancer biomarkers. PMID- 26842752 TI - Predicative Factors for Corneal Endothelial Cell Migration. AB - PURPOSE: To characterize the effects of Descemet's stripping, Rho-associated protein kinase inhibitor Y-27632, and donor age on endothelial migration in human corneas maintained in ex vivo culture. METHODS: Twenty-eight cadaveric human corneas underwent ex vivo culture in either standard or Y-27632-supplemented culture medium for 14 days. The posterior surface of each cornea was manipulated to create two types of wounds: scratched wound--corneal endothelial cells (CECs) were denuded from the Descemet's membrane (DM) to leave behind a bare but intact DM; and peeled wound--both the DM and overlying CECs were stripped to leave behind bare corneal stroma. Endothelial migration was assessed via Trypan blue staining. Morphologic traits of CECs were assessed via Alizarin red microscopy and scanning electron microscopy. RESULTS: The CECs migrated preferentially over scratched wounds compared with peeled wounds. Y-27632 supplementation accelerated endothelial migration over scratched wounds. Endothelial migration decreased with advanced donor age for both wound types, regardless of exposure to Y-27632. Y 27632 supplementation resulted in a less rapid decline in endothelial migration for donors older than 50 years of age for scratched surfaces. Greater cell density and hexagonality was observed over scratched wounds compared with peeled wounds, regardless of Y-27632 supplementation. CONCLUSIONS: The presence of an intact DM, Y-27632 supplementation, and young donor age are factors that promote endothelial migration in an ex vivo human cornea culture model. The negative effect of age on endothelial migration can be mitigated by the presence of an intact DM and Y-27632 supplementation. PMID- 26842751 TI - Monitoring patient care through health facility exit interviews: an assessment of the Hawthorne effect in a trial of adherence to malaria treatment guidelines in Tanzania. AB - BACKGROUND: Survey of patients exiting health facilities is a common way to assess consultation practices. It is, however, unclear to what extent health professionals may change their practices when they are aware of such interviews taking place, possibly paying more attention to following recommended practices. This so-called Hawthorne effect could have important consequences for interpreting research and programme monitoring, but has rarely been assessed. METHODS: A three-arm cluster-randomised trial of interventions to improve adherence to guidelines for the use of anti-malarial drugs was conducted in Tanzania. Patient interviews were conducted outside health facilities on two randomly-selected days per week. Health workers also routinely documented consultations in their ledgers. The Hawthorne effect was investigated by comparing routine data according to whether exit interviews had been conducted on three key indicators of malaria care. Adjusted logistic mixed-effects models were used, taking into account the dependencies within health facilities and calendar days. RESULTS: Routine data were collected on 19,579 consultations in 18 facilities. The odds of having a malaria rapid diagnostic test (RDT) result reported were 11 % higher on days when exit surveys were conducted (adjusted odds ratio 95 % CI: 0.98-1.26, p = 0.097), 17 % lower for prescribing an anti-malarial drug to patients with a negative RDT result (0.56-1.23, p = 0.343), and 27 % lower for prescribing an anti-malarial when no RDT result was reported (0.53 1.00, p = 0.052). The effect varied with time, with a U-shaped association over the study period (p < 0.001). We also observed a higher number of consultations recorded on days when exit-interviews were conducted (adjusted mean difference = 2.03, p < 0.001). CONCLUSIONS: Although modest, there was some suggestion of better practice by health professionals on days when exit interviews were conducted. Researchers should be aware of the potential Hawthorne effect, and take into account assessment methods when generalising findings to the 'real word' setting. This effect is, however, likely to be context dependent, and further controlled evaluation across different settings should be conducted. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01292707 . Registered on 29th January 2011. PMID- 26842753 TI - Autosomal Dominant Retinal Dystrophies Caused by a Founder Splice Site Mutation, c.828+3A>T, in PRPH2 and Protein Haplotypes in trans as Modifiers. AB - PURPOSE: We determined the phenotypic variation, disease progression, and potential modifiers of autosomal dominant retinal dystrophies caused by a splice site founder mutation, c.828+3A>T, in the PRPH2 gene. METHODS: A total of 62 individuals (19 families) harboring the PRPH2 c.828+3A>T mutation, had phenotype analysis by fundus appearance, electrophysiology, and visual fields. The PRPH2 haplotypes in trans were sequenced for potential modifying variants and generalized estimating equations (GEE) used for statistical analysis. RESULTS: Several distinct phenotypes caused by the PRPH2 c.828+3A>T mutation were observed and fell into two clinical categories: Group I (N = 44) with mild pattern dystrophies (PD) and Group II (N = 18) with more severe cone-rod dystrophy (CRD), retinitis pigmentosa (RP), and central areolar chorioretinal dystrophy (CACD). The PRPH2 Gln304-Lys310-Asp338 protein haplotype in trans was found in Group I only (29.6% vs. 0%), whereas the Glu304-Lys310-Gly338 haplotype was predominant in Group II (94.4% vs. 70.4%). Generalized estimating equations analysis for PD versus the CRD/CACD/RP phenotypes in individuals over 43 years alone with the PRPH2 haplotypes in trans and age as predictors, adjusted for correlation within families, confirmed a significant effect of haplotype on severity (P = 0.03) with an estimated odds ratio of 7.16 (95% confidence interval [CI] = [2.8, 18.4]). CONCLUSIONS: The PRPH2 c.828+3A>T mutation results in multiple distinct phenotypes likely modified by protein haplotypes in trans; the odds of having the CACD/RP-like phenotype (versus the PD phenotype) are 7.16 times greater with a Glu304-Lys310-Gly338 haplotype in trans. Further functional studies of the modifying haplotypes in trans and PRPH2 splice variants may offer therapeutic targets. PMID- 26842756 TI - Flicker Sensitivity in Normal Aging--Monocular Tests of Retinal Function at Photopic and Mesopic Light Levels. AB - PURPOSE: Aging can affect many aspects of visual performance. In general, the effects become more significant in those older than 40 to 50 years, with increased intersubject variability and stronger dependence on ambient illumination. This study aimed to establish how healthy aging of the retina affects the detection of 15-Hz flicker under photopic and mesopic lighting. METHODS: We investigated 71 participants aged 20 to 75 years. Thresholds were measured for detection of 15-Hz flicker at the fovea (0 degrees ) and at an eccentricity of 4 degrees in each of the four quadrants. The background luminance ranged from 0.6 to 60 cd/m(2) and pupil size was measured continuously. Participants were excluded if they had signs/history of ocular disease, substantial interocular differences in flicker thresholds, or were unable to detect 100% flicker modulation in the high mesopic range. RESULTS: Mesopic and photopic flicker thresholds were used to calculate an index, the health of the retina index, to determine the limits of flicker sensitivity in healthy aging. Log flicker thresholds changed bilinearly with age; they remained stable until 40 to 50 years, with a linear decline with increasing age. This bilinear pattern of the change in flicker thresholds with age is consistent across photopic and mesopic light levels. CONCLUSIONS: The health of the retina index captures the lowest threshold, usually obtained under photopic conditions, as well as the loss of flicker sensitivity with decreasing light level. The established limits of healthy aging may benefit from future studies in patients with ocular hypertension and/or glaucoma that are known to experience loss of flicker sensitivity. PMID- 26842754 TI - N-Acetylcysteine Amide Protects Against Oxidative Stress-Induced Microparticle Release From Human Retinal Pigment Epithelial Cells. AB - PURPOSE: Oxidative stress is a major factor involved in retinal pigment epithelium (RPE) apoptosis that underlies AMD. Drusen, extracellular lipid- and protein-containing deposits, are strongly associated with the development of AMD. Cell-derived microparticles (MPs) are small membrane-bound vesicles shed from cells. The purpose of this study was to determine if oxidative stress drives MP release from RPE cells, to assess whether these MPs carry membrane complement regulatory proteins (mCRPs: CD46, CD55, and CD59), and to evaluate the effects of a thiol antioxidant on oxidative stress-induced MP release. METHODS: Retinal pigment epithelium cells isolated from human donor eyes were cultured and treated with hydrogen peroxide (H2O2) to induce oxidative stress. Isolated MPs were fixed for transmission electron microscopy or processed for component analysis by flow cytometry, Western blot analysis, and confocal microscopy. RESULTS: Transmission electron microscopy showed that MPs ranged in diameter from 100 to 1000 nm. H2O2 treatment led to time- and dose-dependent elevations in MPs with externalized phosphatidylserine and phosphatidylethanolamine, known markers of MPs. These increases were strongly correlated to RPE apoptosis. Oxidative stress significantly increased the release of mCRP-positive MPs, which were prevented by a thiol antioxidant, N-acetylcysteine amide (NACA). CONCLUSIONS: This is the first evidence that oxidative stress induces cultured human RPE cells to release MPs that carry mCRPs on their surface. The levels of released MPs are strongly correlated with RPE apoptosis. N-acetylcysteine amide prevents oxidative stress induced effects. Our findings indicate that oxidative stress reduces mCRPs on the RPE surface through releasing MPs. PMID- 26842755 TI - Targeting the Nrf2 Signaling Pathway in the Retina With a Gene-Delivered Secretable and Cell-Penetrating Peptide. AB - PURPOSE: Oxidative stress has been linked to several ocular diseases, initiating an inflammatory response that increases tissue injury. The Nrf2 transcription factor regulates expression of antioxidant genes and is tightly regulated by Kelch-Like ECH-Associated Protein 1 (Keap-1). We evaluate the antioxidant and anti-inflammatory properties of an adeno-associated virus (AAV) vector delivering an Nrf2-derived peptide that binds Keap-1. METHODS: The sequence of the Nrf2 peptide was fused to a cell-penetrating peptide (Tat-peptide) sequence (TatNrf2mer). The effects of lentiviral-delivered TatNrf2mer were studied in vitro. Transcript (quantitative [q] RT-PCR) and protein levels (ELISA and immunofluorescence) were quantified. Cell viability was measured by MTT and Cell Titer assays. The AAV vectors were packaged with the TatNrf2mer fused to secretable green fluorescent protein (GFP) under the control of the small chicken beta actin promoter. The protective effects of this vector were evaluated in a model of RPE oxidative injury and in a mouse model of uveitis after intravitreal injection. RESULTS: Expression of TatNrf2mer peptide induced antioxidant gene expression, blocked IL-1beta secretion, and protected cells from oxidative injury. In mice, TatNrf2mer expression partially protected photoreceptor function based on ERG responses and optical coherence tomography measurements in the sodium iodate (NaIO3) model. Furthermore, sGFP-TatNrf2mer expression decreased IL 1beta and IL-6 in the NaIO3-treated mice, and resulted in a 54% decrease in the number of inflammatory cells in the vitreous body of the endotoxin-induced uveitis mouse model. CONCLUSIONS: The intravitreally delivered AAV-TatNrf2mer has antioxidant and anti-inflammatory effects in widely-used models of ocular injury, suggesting it also could be useful in ocular diseases associated with oxidative stress and inflammasome activation. PMID- 26842757 TI - Parapapillary Gamma Zone and Axial Elongation-Associated Optic Disc Rotation: The Beijing Eye Study. AB - PURPOSE: The parapapillary gamma zone has been defined as the parapapillary region without Bruch's membrane. We examined which morphologic parameters are associated with the presence and size of the parapapillary gamma zone. METHODS: Using fundus photographs and spectral-domain optical coherence tomographic images of the optic nerve head in the population-based Beijing Eye Study, we determined parapapillary gamma zone width, macular Bruch's membrane length, optic disc-fovea distance, the angle of horizontal optic disc rotation, the angle of vertical optic disc rotation, and the ratio of the vertical-to-horizontal disc diameter. RESULTS: The study included 2068 individuals with a mean age of 63.0 +/- 9.0 years (range, 50-91 years), and mean axial length was 23.2 +/- 1.0 mm (range, 18.96-28.87 mm). In multivariate analysis, larger width of parapapillary gamma zone was associated with more marked vertical optic disc rotation (P < 0.001; standardized correlation coefficient beta, 0.15; nonstandardized correlation coefficient B, 0.02; 95% confidence interval [CI], 0.02, 0.03), more marked horizontal optic disc rotation (P = 0.02; beta, 0.05; B, 0.01; 95% CI, 0.001, 0.01), longer axial length (P = 0.01; beta, 0.07; B, 0.02; 95% CI, 0.01, 0.04), longer horizontal optic disc diameter (P = 0.02; beta, 0.05; B, 0.06; 95% CI, 0.01, 0.12), longer disc-fovea distance (P < 0.001; beta, 0.25; B, 0.22; 95% CI, 0.18, 0.27), higher degree of fundus tessellation (P = 0.03; beta, 0.17; B, 0.04; 95% CI, 0.03, 0.0), and thinner subfoveal choroidal thickness (P < 0.001; beta, 0.13; B, 0.000; 95% CI, -0.001, 0.000). Parapapillary gamma zone width was not significantly associated with macular Bruch's membrane length (P = 0.72), disc fovea angle (P = 0.62), age (P = 0.62), or sex (P = 0.46). CONCLUSIONS: The parapapillary gamma zone was associated with an axial elongation-induced rotation of the optic disc mainly around the vertical disc axis, leading to a stretching of the temporal peripapillary scleral flange. Because macular Bruch's membrane length was independent of axial elongation, it leaves the temporal parapapillary region with an uncovered Bruch's membrane (i.e., parapapillary gamma zone develops). PMID- 26842759 TI - Isolated anterior mediastinal tuberculosis in an immunocompetent patient. AB - BACKGROUND: The differential diagnosis of a mediastinal mass is a common challenge in clinical practice, with a wide range of differential diagnosis to be considered. One of the rarer causes is tuberculosis. Atypical presentations of tuberculosis are well documented in immunocompromised patients, but should also be considered in the immunocompetent. CASE PRESENTATION: This case outlines a previously healthy 22 year-old immunocompetent male presenting with worsening chest pain, positional dyspnea, dry cough and dysphagia. Chest x-ray showed evidence of an isolated anterior mediastinal mass, which was confirmed on computed tomography. A mediastinoscopy was diagnostic as histology revealed necrotizing granulomatous inflammation and the presence of acid-fast bacilli, indicating mediastinal tuberculosis. CONCLUSION: Typically the underlying presentation of mediastinal tuberculosis is mediastinal lymphadenitis. This case was unusual in that we detected an isolated large anterior mediastinal mass accompanied by a relatively small burden of mediastinal lymphadenitis. Cases similar to this have been documented in immunosuppressed patients however in our case no evidence of immunosuppression was found. This case report emphasizes the importance that a detailed and logical pathway of investigation is pursued when encountering a mediastinal mass. PMID- 26842760 TI - A Comparative Effectiveness Analysis of the Implementation of Surgical Safety Checklists in a Tertiary Care Hospital. AB - IMPORTANCE: The appropriately coached implementation of surgical safety checklists (SSCs) reduces the incidence of perioperative complications and 30-day mortality of patients undergoing surgery. The association of the introduction of SSCs with 90-day mortality remains unclear. OBJECTIVE: To assess the association between the implementation of SSCs and all-cause 90- and 30-day mortality rates. DESIGN, SETTING, AND PARTICIPANTS: Evaluation of the outcomes of surgical procedures performed during the 6 months before (January 1 to June 30, 2010) and after (January 1 to June 30, 2013) the introduction of SSCs by retrospective analysis of administrative databases. The study was conducted in a public, regional, university-affiliated hospital in Italy. Data were collected from October 23, 2013, to November 12, 2014, including 90-day all-cause mortality, 30 day all-cause mortality, length of hospital stay, and 30-day readmission rate among patients undergoing noncardiac surgery. Patients undergoing surgery during the 6-month periods before and after the implementation of SSCs were compared. Data were analyzed from September 17, 2014, to July 31, 2015. MAIN OUTCOMES AND MEASURES: Risk-adjusted rates of 90- and 30-day mortality, readmission rate, and length of stay. RESULTS: The total study sample of 10 741 patients included 5444 preintervention and 5297 postintervention patients (5093 [47.4%] male and 5648 [52.6%] female patients; mean [SD] age, 53.0 [23.0] years). Ninety-day all-cause mortality was 2.4% (129 patients) before compared with 2.2% (118 patients) after the SSC implementation, for an adjusted odds ratio (AOR) of 0.73 (95% CI, 0.56 0.96; P = .02). Thirty-day all-cause mortality was 1.36% (74 patients) before compared with 1.32% (70 patients) after the SSC implementation, for an AOR of 0.79 (95% CI, 0.56-1.11; P = .17). Thirty-day readmission occurred in 797 patients (14.6%) in the preimplementation group vs 766 patients (14.5%) in the postimplementation group, for an AOR of 0.90 (95% CI, 0.81-1.01; P = .79). The adjusted length of stay was 10.4 (95% CI, 10.3-10.6) days in the preimplementation group compared with 9.6 (95% CI, 9.4-9.7) days in the postimplementation group (P < .001). CONCLUSIONS AND RELEVANCE: The data cannot prove causality owing to the study design. The implementation of SSCs was associated with a 27% reduction of the adjusted risk for all-cause death within 90 days but not within 30 days. The adjusted length of stay was reduced after implementation of SSCs. PMID- 26842758 TI - Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability. AB - Topoisomerase 1, an enzyme that relieves superhelical tension, is implicated in transcription-associated mutagenesis and genome instability-associated with neurodegenerative diseases as well as activation-induced cytidine deaminase. From proteomic analysis of TOP1-associated proteins, we identify SMARCA4, an ATP dependent chromatin remodeller; FACT, a histone chaperone; and H3K4me3, a transcriptionally active chromatin marker. Here we show that SMARCA4 knockdown in a B-cell line decreases TOP1 recruitment to chromatin, and leads to increases in Igh/c-Myc chromosomal translocations, variable and switch region mutations and negative superhelicity, all of which are also observed in response to TOP1 knockdown. In contrast, FACT knockdown inhibits association of TOP1 with H3K4me3, and severely reduces DNA cleavage and Igh/c-Myc translocations, without significant effect on TOP1 recruitment to chromatin. We thus propose that SMARCA4 is involved in the TOP1 recruitment to general chromatin, whereas FACT is required for TOP1 binding to H3K4me3 at non-B DNA containing chromatin for the site-specific cleavage. PMID- 26842761 TI - Portable Wideband Microwave Imaging System for Intracranial Hemorrhage Detection Using Improved Back-projection Algorithm with Model of Effective Head Permittivity. AB - Intracranial hemorrhage is a medical emergency that requires rapid detection and medication to restrict any brain damage to minimal. Here, an effective wideband microwave head imaging system for on-the-spot detection of intracranial hemorrhage is presented. The operation of the system relies on the dielectric contrast between healthy brain tissues and a hemorrhage that causes a strong microwave scattering. The system uses a compact sensing antenna, which has an ultra-wideband operation with directional radiation, and a portable, compact microwave transceiver for signal transmission and data acquisition. The collected data is processed to create a clear image of the brain using an improved back projection algorithm, which is based on a novel effective head permittivity model. The system is verified in realistic simulation and experimental environments using anatomically and electrically realistic human head phantoms. Quantitative and qualitative comparisons between the images from the proposed and existing algorithms demonstrate significant improvements in detection and localization accuracy. The radiation and thermal safety of the system are examined and verified. Initial human tests are conducted on healthy subjects with different head sizes. The reconstructed images are statistically analyzed and absence of false positive results indicate the efficacy of the proposed system in future preclinical trials. PMID- 26842762 TI - Positive association between IL-16 rs1131445 polymorphism and cancer risk: a meta analysis. AB - INTRODUCTION: The association between IL-16 rs1131445 polymorphism and cancer risk is not consistent or even contradictory, this meta-analysis aims to investigate the role of IL-16 gene rs1131445 polymorphisms in the risk of cancer. EVIDENCE ACQUISITION: A comprehensive online search was conducted in PubMed, EMBASE and CNKI databases to identify eligible studies. The case-control studies related IL-16 rs1131445 C/T polymorphism with the cancer susceptibility were selected according to the inclusion and exclusion criteria. After extracting the basic data information and quality of literature evaluation, the meta-analysis was performed by using STATA 12.0 software, with calculating odds ratio and 95% confidence interval, and further subgroup analysis, literature publication bias test and sensitivity analysis. EVIDENCE SYNTHESIS: There are totally 1677 cases and 1989 non-tumor controls finally involved. Meta-analysis showed that there are statistical correlations between the IL-16 rs1131445 C/T polymorphism and the cancer risk in Asian populations (TS vs. C, OR=0.80, 95%CI: 0.73-0.88; TT vs. TC, OR=0.75, 95%CI: 0.65-0.87; TT vs. CC, OR=0.69, 95% CI: 0.56-0.84; CC+TC vs. TT, OR=1.36, 95%CI: 1.19-1.55; CC vs. TC+TT, OR=1.27, 95%CI: 1.05-1.53) (all P<0.05). CONCLUSIONS: IL-16 rs1131445 C/T polymorphism is related to the susceptibility to cancer in Asians, suggesting that the C allelic gene of rs1131445 is significantly associated with an increasing cancer risk. PMID- 26842763 TI - Quantitative assessment of the association between interleukin-10 promoter gene polymorphisms and nasopharyngeal carcinoma susceptibility. AB - INTRODUCTION: Previous studies about the possible link between genetic polymorphisms of interleukin-10 (IL-10) and nasopharyngeal carcinoma (NPC) risk offer controversial results, and the sample sizes recruited in these trials were relatively modest. To further determine this association, a comprehensive analysis was performed in the present study. EVIDENCE ACQUISITION: Eligible studies were selected from PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), China Biological Medicine Database and Wanfang Database. A total of 623 cases and 1,018 controls for the IL-10 -1082G/A polymorphism, 463 cases and 862 controls for the IL-10 -819T/C polymorphism, and 463 cases and 862 controls for the IL-10 -592A/C polymorphism were finally included in this meta analysis. EVIDENCE SYNTHESIS: Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association by fixed effects or random-effects models according to heterogeneity. In the present analysis, a strong relationship between the -1082G/A polymorphism in IL-10 promoter and NPC susceptibility was found in all genetic models [allele, 0.65 (0.45-0.94), P=0.02; co-dominant, 0.15 (0.06-0.38), P<0.0001;, dominant 14.37 (2.86-72.09), P=0.001; and recessive fashions, 0.56 (0.45-0.71), P<0.0001)]. However, NPC risk was linked to -592A/C or -819T/C polymorphism in IL-10 promoter only in the co-dominant model in both genetic situations [for -819T/C, 0.36 (0.17 0.78), P=0.01; for -592A/C, 0.39 (0.19-0.80), P=0.01]. CONCLUSIONS: Our study has shown that the IL-10 -1082G/A polymorphism might be associated with increased risk of NPC under all genetic models. However, NPC risk is linked to -592A/C or 819T/C polymorphism in IL-10 promoter only in the co-dominant model in both genetic situations. PMID- 26842764 TI - Low expression of long non-coding RNA-LET can indicate metastasis and a poor prognosis: a meta-analysis. AB - BACKGROUND: Recent studies have reported that the lncRNA-LET was down-regulated in several cancers.The current meta-analysis aims to determine whether lncRNA-LET can be used as a potential biomarker for metastasis and prognosis. METHODS: We collected all relevant papers by searching multiple electronic databases(Pubmed,EMBASE,Google Scholar,CNKI,Wanfang database) and explored the association between the expression levels of lncRNA-LETand lymph node metastasis (LNM),distant metastasis (DM) and overall survival (OS). RESULTS: A total of 383 patients from four studies were finally included.The meta-analysis results showed that LNM occurred more frequently in patients with low lncRNA-LET expression group than in patients with high lncRNA-LET expression group(OR=4.56,95%CI:2.92 7.12,p<0.00001),and a similar result was observed between lncRNA-LET expression and DM,the OR was 4.77(95%CI:2.29-9.94, p<0.0001).Additionally,we found that patient with low lncRNA-LET expression had a poorer OS than those high lncRNA-LET expression (HR=2.39,95 %CI:1.57-3.21,p = 0.000). CONCLUSION: LncRNA-LETmay serve as a common molecular marker for metastasis and prognosis in human cancers. PMID- 26842765 TI - Phenolic environmental estrogens in urine and blood plasma from women with uterine leiomyoma: Epidemiological survey. AB - AIM: To explore the effect of phenolic environmental estrogens (EE) on women with uterine leiomyoma (UL). METHODS: Urine and blood plasma samples were collected from 300 patients diagnosed with UL at the Affiliated Zhongda Hospital of Southeast University between December 2013 and December 2014. Control urine and blood plasma samples were collected from 300 women who are either patients without UL or healthy volunteers presenting to the same hospital for physical examination during the same period. Bisphenol A (BPA), nonylphenol (NP) and octylphenol (OP) concentration in these samples was measured using solid phase extraction (SPE) coupled with liquid chromatography-tandem mass spectrometry. RESULTS: The OP concentration in urine and blood plasma was significantly higher in the UL group compared with the control group (r = 0.224, P = 0.001). Urine BPA concentration was not significantly different between the UL group and the control group (r = 0.009, P = 0.896). There was also no statistically significant difference in urine NP concentration between the two groups (r = 0.057, P = 0.419). On logistic regression, exposure concentration of urine BPA (OR, 1.129; 95%CI: 1.081-1.179) and NP (OR, 1.165; 95%CI: 1.025-1.324) was associated with UL genesis (P < 0.05). Nevertheless, there was no significant difference in blood plasma concentration of BPA, OP and NP between the two groups (P > 0.05). CONCLUSION: Urine and blood plasma EE exposure levels in women, especially the urine level, was related to the incidence of UL. PMID- 26842767 TI - g2pDB: A Database Mapping Protein Post-Translational Modifications to Genomic Coordinates. AB - Large scale proteomics have made it possible to broadly screen samples for the presence of many types of post-translational modifications, such as phosphorylation, acetylation, and ubiquitination. This type of data has allowed the localization of these modifications to either a specific site on a proteolytically generated peptide or to within a small domain on the peptide. The resulting modification acceptor sites can then be mapped onto the appropriate protein sequences and the information archived. This paper describes the usage of a very large archive of experimental observations of human post-translational modifications to create a map of the most reproducible modification observations onto the complete set of human protein sequences. This set of modification acceptor sites was then directly translated into the genomic coordinates for the codons for the residues at those sites. We constructed the database g2pDB using this protein-to-codon site mapping information. The information in g2pDB has been made available through a RESTful-style API, allowing researchers to determine which specific protein modifications would be perturbed by a set of observed nucleotide variants determined by high throughput DNA or RNA sequencing. PMID- 26842766 TI - Antimicrobial Activity of the Manganese Photoactivated Carbon Monoxide-Releasing Molecule [Mn(CO)3(tpa-kappa(3)N)](+) Against a Pathogenic Escherichia coli that Causes Urinary Infections. AB - AIMS: We set out to investigate the antibacterial activity of a new Mn-based photoactivated carbon monoxide-releasing molecule (PhotoCORM, [Mn(CO)3(tpa kappa(3)N)](+)) against an antibiotic-resistant uropathogenic strain (EC958) of Escherichia coli. RESULTS: Activated PhotoCORM inhibits growth and decreases viability of E. coli EC958, but non-illuminated carbon monoxide-releasing molecule (CORM) is without effect. NADH-supported respiration rates are significantly decreased by activated PhotoCORM, mimicking the effect of dissolved CO gas. CO from the PhotoCORM binds to intracellular targets, namely respiratory oxidases in strain EC958 and a bacterial globin heterologously expressed in strain K-12. However, unlike previously characterized CORMs, the PhotoCORM is not significantly accumulated in cells, as deduced from the cellular manganese content. Activated PhotoCORM reacts avidly with hydrogen peroxide producing hydroxyl radicals; the observed peroxide-enhanced toxicity of the PhotoCORM is ameliorated by thiourea. The PhotoCORM also potentiates the effect of the antibiotic, doxycycline. INNOVATION: The present work investigates for the first time the antimicrobial activity of a light-activated PhotoCORM against an antibiotic-resistant pathogen. A comprehensive study of the effects of the PhotoCORM and its derivative molecules upon illumination is performed and mechanisms of toxicity of the activated PhotoCORM are investigated. CONCLUSION: The PhotoCORM allows a site-specific and time-controlled release of CO in bacterial cultures and has the potential to provide much needed information on the generality of CORM activities in biology. Understanding the mechanism(s) of activated PhotoCORM toxicity will be key in exploring the potential of this and similar compounds as antimicrobial agents, perhaps in combinatorial therapies with other agents. Antioxid. Redox Signal. 24, 765-780. PMID- 26842769 TI - Bioactive clusters promoting cell penetration and nucleic acid complexation for drug and gene delivery applications: from designed to self-assembled and responsive systems. AB - Bioactive low-molecular-weight compounds are actively pursued, as an alternative to macromolecules, for biomedical applications such as drug and gene delivery. However, achieving effective biomolecular surface recognition with small molecules is a considerable challenge. We review herein recent progresses that have been made in the identification of bioactive cationic clusters that promote cell penetration and nucleic acid complexation and vectorisation. We further emphasize the emerging use of self-assembly processes, based on supramolecular interactions and/or dynamic covalent chemistry, for generating bioactive cationic clusters. Interestingly, the introduction of molecular and/or supramolecular dynamics endows reversibility to the multivalent recognition processes, thereby paving the way toward the development of "smart" adaptive and responsive devices that emulate the behaviour of natural systems for the dynamic control of bioactivity. PMID- 26842768 TI - Bosma arhinia microphthalmia syndrome: Clinical report and review of the literature. AB - Bosma arhinia microphthalmia syndrome (Bosma syndrome)(OMIM 603457) is a congenital condition characterized by microphthalmia with coloboma, arhinia and endocrine findings in the setting of normal intelligence and brain structure. This condition is quite rare with fewer than 50 case reports and series. Although pathogenesis is presumed to be genetic, the cause remains unknown. We report an individual with Bosma syndrome who had bilateral colobomatous microphthalmia, arhinia, high arched palate, mild ear malformations, and hypogonadotropic hypogonadism requiring growth hormone treatment in childhood, and normal intelligence. Clinical evaluation was significant for a geometrically abnormal aorta with effacement of the sinotubular ridge, a finding not previously reported in this condition. An MRI revealed absent olfactory bulbs. Suggested criteria for diagnosis of Bosma should include arhinia, hypoplastic maxilla, normal cognition, and hypogonadotropic hypogonadism in males. PMID- 26842770 TI - Brain radiation injury leads to a dose- and time-dependent recruitment of peripheral myeloid cells that depends on CCR2 signaling. AB - BACKGROUND: Cranial radiotherapy is used to treat tumors of the central nervous system (CNS), as well as non-neoplastic conditions such as arterio-venous malformations; however, its use is limited by the tolerance of adjacent normal CNS tissue, which can lead to devastating long-term sequelae for patients. Despite decades of research, the underlying mechanisms by which radiation induces CNS tissue injury remain unclear. Neuroinflammation and immune cell infiltration are a recognized component of the CNS radiation response; however, the extent and mechanisms by which bone marrow-derived (BMD) immune cells participate in late radiation injury is unknown. Thus, we set out to better characterize the response and tested the hypothesis that C-C chemokine receptor type 2 (CCR2) signaling was required for myeloid cell recruitment following brain irradiation. METHODS: We used young adult C57BL/6 male bone marrow chimeric mice created with donor mice that constitutively express enhanced green fluorescent protein (eGFP). The head was shielded to avoid brain radiation exposure during chimera construction. Radiation dose and time response studies were conducted in wild-type chimeras, and additional experiments were performed with chimeras created using donor marrow from CCR2 deficient, eGFP-expressing mice. Infiltrating eGFP+ cells were identified and quantified using immunofluorescent microscopy. RESULTS: Brain irradiation resulted in a dose- and time-dependent infiltration of BMD immune cells (predominately myeloid) that began at 1 month and persisted until 6 months following >=15 Gy brain irradiation. Infiltration was limited to areas that were directly exposed to radiation. CCR2 signaling loss resulted in decreased numbers of infiltrating cells at 6 months that appeared to be restricted to cells also expressing major histocompatibility complex class II molecules. CONCLUSIONS: The potential roles played by infiltrating immune cells are of current importance due to increasing interest in immunotherapeutic approaches for cancer treatment and a growing clinical interest in survivorship and quality of life issues. Our findings demonstrate that injury from brain radiation facilitates a dose- and time-dependent recruitment of BMD cells that persists for at least 6 months and, in the case of myeloid cells, is dependent on CCR2 signaling. PMID- 26842772 TI - Design of crystal-like aperiodic solids with selective disorder-phonon coupling. AB - Functional materials design normally focuses on structurally ordered systems because disorder is considered detrimental to many functional properties. Here we challenge this paradigm by showing that particular types of strongly correlated disorder can give rise to useful characteristics that are inaccessible to ordered states. A judicious combination of low-symmetry building unit and high-symmetry topological template leads to aperiodic 'procrystalline' solids that harbour this type of disorder. We identify key classes of procrystalline states together with their characteristic diffraction behaviour, and establish mappings onto known and target materials. The strongly correlated disorder found in these systems is associated with specific sets of modulation periodicities distributed throughout the Brillouin zone. Lattice dynamical calculations reveal selective disorder driven phonon broadening that resembles the poorly understood 'waterfall' effect observed in relaxor ferroelectrics. This property of procrystalline solids suggests a mechanism by which strongly correlated topological disorder might allow independently optimized thermal and electronic transport behaviour, such as required for high-performance thermoelectrics. PMID- 26842771 TI - A dose-response evaluation of freeze-dried strawberries independent of fiber content on metabolic indices in abdominally obese individuals with insulin resistance in a randomized, single-blinded, diet-controlled crossover trial. AB - SCOPE: This study evaluated the dose-response relationship of strawberries, an anthocyanin-rich fruit, on postprandial glucose and insulin concentrations in individuals with insulin resistance (IR), including changes in plasma anthocyanins, markers of oxidative stress, and inflammation. METHODS AND RESULTS: In a randomized controlled, four-arm, dose-response, crossover trial, 21 adults with IR consumed a high-carbohydrate, high-fat meal with one of four beverages containing 0 g freeze-dried whole strawberry powder (0g FDS, control), 10, 20, or 40 g FDS, controlled for fiber. Blood was collected at 0 min and at 30 min intervals postmeal until 2 h, then hourly until 6 h. Postmeal insulin concentrations (6 h) were significantly reduced after the 40-g FDS beverage compared to other beverages (p < 0.05). Postmeal 6 h glucose concentrations were not different, although mean insulin:glucose ratio was significantly different among beverages (p < 0.05). Pelargonidin-glucuronide was inversely associated with mean insulin concentrations after the 20 and 40 g FDS (p < 0.05). Oxidized low-density lipoprotein was reduced after 20 g FDS (p < 0.05) and IL-6 was not different among treatments. Strawberry intake reduced the insulin demand to manage postmeal glucose in obese individuals with IR, which was related to plasma anthocyanin/pelargonidin concentrations. CONCLUSION: The data support a role of strawberries in improving insulin sensitivity in people with IR. PMID- 26842773 TI - Prospective investigation on the transfer of Ara h 2, the most potent peanut allergen, in human breast milk. AB - BACKGROUND: Peanut allergy is one of the most severe food allergies. Whether breastfeeding induces tolerance to peanuts or on the contrary, pre-disposes at risk-babies to occult allergic sensitization to peanuts is still a matter of discussion. We sought to investigate the transfer of the most potent peanut allergen Ara h 2 into human breast milk in a German breast milk study and to shed light on the time kinetics of Ara h 2 appearance. METHODS: We recruited 32 lactating, non-peanut-allergic women and collected breast milk samples at different time points after consumption of 100 g dry roasted peanuts. Breast milk samples were investigated for Ara h 2 with different immunological methods: by 2D immunoblotting with a patient's serum, by affinity enrichment using a monoclonal antibody against Ara h 2 followed by LC-MS/MS-based detection and by a competitive inhibition ELISA for the detection of Ara h 2 and its digestion resistant peptides (DRP-Ara h 2). RESULTS: In a qualitative analysis, Ara h 2 could be identified in a breast milk sample by 2D immunoblot by means of a patient's serum and furthermore by immunoaffinity enrichment followed by LC-MS/MS analysis. In a semi-quantitative analysis, Ara h 2 and its digestion-resistant peptides were detected in the breast milk of 9 of 32 subjects. Evidence suggests that Ara h 2 is excreted individually either rapidly (after 1, 2, 3 or 4 h) or delayed (after 8 or 12 h) and in different concentrations. CONCLUSIONS: Time and concentration of secreted Ara h 2 in breast milk appears to be individually regulated. The identification of Ara h 2 in breast milk is the prerequisite for the investigation of its sensitizing or tolerogenic properties. PMID- 26842774 TI - The evolution of sex roles in mate searching. AB - Searching for mates is a critical stage in the life cycle of most internally, and many externally, fertilizing species. Males usually invest more in this costly activity than females, but the reasons for this are poorly understood. Previous models have shown that female-biased parental investment, including anisogamy, does not by itself select for male-biased mate searching, so it requires additional explanations. Here, we correct and expand upon earlier models, and present two novel hypotheses that might explain the evolution of male-biased mate searching. The "carry-over hypothesis" states that females benefit less from searching if the associated costs affect other stages of the life cycle, rather than arising only while searching. It is relevant to the evolution of morphological traits that improve searching efficiency but are also expressed in other contexts. The "mating window hypothesis" states that females benefit less from searching if their life cycle includes intervals during which the exact timing of mating does not matter for the appropriate timing of reproduction (e.g., due to sperm storage or delayed embryo implantation). Such intervals are more likely to exist for females given the general pattern of greater female parental investment. Our models shed new light on classic arguments about sex role evolution. PMID- 26842775 TI - Infections in Australian Aged-Care Facilities: Evaluating the Impact of Revised McGeer Criteria for Surveillance of Urinary Tract Infections. AB - Our survey of 112 Australian aged-care facilities demonstrated the prevalence of healthcare-associated infections to be 2.9%. Urinary tract infections (UTIs) defined by McGeer criteria comprised 35% of all clinically defined UTIs. To estimate the infection burden in these facilities where microbiologic testing is not routine, modified surveillance criteria for UTIs are necessary. PMID- 26842776 TI - Emergence of the mcr-1 colistin resistance gene in carbapenem-resistant Enterobacteriaceae. PMID- 26842777 TI - Carbapenem-resistant and colistin-resistant Escherichia coli co-producing NDM-9 and MCR-1. PMID- 26842778 TI - New insights into the protein aggregation pathology in myotilinopathy by combined proteomic and immunolocalization analyses. AB - INTRODUCTION: Myofibrillar myopathies are characterized by progressive muscle weakness and impressive abnormal protein aggregation in muscle fibers. In about 10 % of patients, the disease is caused by mutations in the MYOT gene encoding myotilin. The aim of our study was to decipher the composition of protein deposits in myotilinopathy to get new information about aggregate pathology. RESULTS: Skeletal muscle samples from 15 myotilinopathy patients were included in the study. Aggregate and control samples were collected from muscle sections by laser microdissection and subsequently analyzed by a highly sensitive proteomic approach that enables a relative protein quantification. In total 1002 different proteins were detected. Seventy-six proteins showed a significant over representation in aggregate samples including 66 newly identified aggregate proteins. Z-disc-associated proteins were the most abundant aggregate components, followed by sarcolemmal and extracellular matrix proteins, proteins involved in protein quality control and degradation, and proteins with a function in actin dynamics or cytoskeletal transport. Forty over-represented proteins were evaluated by immunolocalization studies. These analyses validated our mass spectrometric data and revealed different regions of protein accumulation in abnormal muscle fibers. Comparison of data from our proteomic analysis in myotilinopathy with findings in other myofibrillar myopathy subtypes indicates a characteristic basic pattern of aggregate composition and resulted in identification of a highly sensitive and specific diagnostic marker for myotilinopathy. CONCLUSIONS: Our findings i) indicate that main protein components of aggregates belong to a network of interacting proteins, ii) provide new insights into the complex regulation of protein degradation in myotilinopathy that may be relevant for new treatment strategies, iii) imply a combination of a toxic gain-of-function leading to myotilin-positive protein aggregates and a loss of-function caused by a shift in subcellular distribution with a deficiency of myotilin at Z-discs that impairs the integrity of myofibrils, and iv) demonstrate that proteomic analysis can be helpful in differential diagnosis of protein aggregate myopathies. PMID- 26842780 TI - Activating Transcription Factor-6alpha Deletion Modulates the Endoplasmic Reticulum Stress Response after Spinal Cord Injury but Does Not Affect Locomotor Recovery. AB - The endoplasmic reticulum stress response (ERSR) is activated in a variety of neurodegenerative diseases and/or traumatic injuries. Subsequent restoration of ER homeostasis may contribute to improvement in the functional outcome of these diseases. We recently demonstrated improvements in hindlimb locomotion after thoracic spinal cord injury (SCI) and implicated oligodendrocyte survival as a potential mechanism using genetic and pharmacological inhibition of the protein kinase ribonucleic acid-like ER kinase- CCAAT/enhancer binding homologous protein (PERK-CHOP) arm of the ERSR. Here, we investigated the contribution of activating transcription factor-6 (ATF6), an ERSR signaling effector comprising the second arm of ERSR, in the pathogenesis of SCI. In contrast to what was seen after attenuation of PERK-CHOP signaling, genetic ablation of ATF6 results in modulation of ERSR and decreased survival in oligodendrocyte precursor cells against ER stress. Further, ATF6 loss delays the ERSR after SCI, potentiates PERK ATF4-CHOP signaling and fails to improve locomotor deficits. These data suggest that deleting ATF6 levels is unlikely to be a viable therapeutic target to improve functional recovery after SCI. PMID- 26842779 TI - Transcriptional comparison of human induced and primary midbrain dopaminergic neurons. AB - Generation of induced dopaminergic (iDA) neurons may provide a significant step forward towards cell replacement therapy for Parkinson's disease (PD). To study and compare transcriptional programs of induced cells versus primary DA neurons is a preliminary step towards characterizing human iDA neurons. We have optimized a protocol to efficiently generate iDA neurons from human pluripotent stem cells (hPSCs). We then sequenced the transcriptomes of iDA neurons derived from 6 different hPSC lines and compared them to that of primary midbrain (mDA) neurons. We identified a small subset of genes with altered expression in derived iDA neurons from patients with Parkinson's Disease (PD). We also observed that iDA neurons differ significantly from primary mDA neurons in global gene expression, especially in genes related to neuron maturation level. Results suggest iDA neurons from patient iPSCs could be useful for basic and translational studies, including in vitro modeling of PD. However, further refinement of methods of induction and maturation of neurons may better recapitulate full development of mDA neurons from hPSCs. PMID- 26842782 TI - Revisiting the Thermodynamics of Water Surfaces and the Effects of Surfactant Head Group. AB - It is common knowledge that surfactants lower the surface tension of water. The typical textbook explanation of this phenomenon is that the force of attraction between surfactant and water molecules is less than that between two water molecules; hence the surface contraction force decreases in the presence of surfactants; however, this common description, based on the strength of intermolecular interactions, is overly simplified because it ignores an important thermodynamic function: the surface entropy of water. Here we report separate measurements of water's surface enthalpy and surface entropy in the presence of nonionic, zwitterionic, anionic, and cationic surfactants. While all of these surfactants decreased the surface enthalpy of water by 50-70%, the surface entropy of water could drop to near-zero or even negative values for ionic surfactants. Studies of this zero-entropy state of water surface using phase sensitive sum-frequency generation (SFG) vibrational spectroscopy and molecular dynamics (MD) simulations suggested that the zero-entropy state of the water surface was associated with surfactant-induced ordering of water molecules and enhanced hydrogen bond formation at the water surface. Both effects reduce water molecules' degrees of freedom for motion and thus lower the surface entropy of water. The ability of a surfactant to decrease the surface entropy of water is in the order ionic > zwitterionic > nonionic. For all surfactant head groups surface entropy plays a critical role in determining the surface tension of water. The description of water's surface tension is not complete without considering its surface entropy. PMID- 26842783 TI - Properties of Poly(ethylene glycol) Hydrogels Cross-Linked via Strain-Promoted Alkyne-Azide Cycloaddition (SPAAC). AB - A series of poly(ethylene glycol) (PEG) hydrogels was synthesized using strain promoted alkyne-azide cycloaddition (SPAAC) between PEG chains terminated with either aza-dibenzocyclooctynes or azide functionalities. The gelation process was found to occur rapidly upon mixing the two components in aqueous solution without the need for external stimuli or catalysts, making the system a candidate for use as an injectable hydrogel. The mechanical and rheological properties of these hydrogels were found to be tunable by varying the polymer molecular weight and the number of cross-linking groups per chain. The gelation times of these hydrogels ranged from 10 to 60 s at room temperature. The mass-based swelling ratios varied from 45 to 76 at maximum swelling (relative to the dry state), while the weight percent of polymer in these hydrogels ranged from 1.31 to 2.05%, demonstrating the variations in amount of polymer required to maintain the structural integrity of the gel. Each hydrogel degraded at a different rate in PBS at pH = 7.4, with degradation times ranging from 1 to 35 days. By changing the composition of the two starting components, it was found that the Young's modulus of each hydrogel could be varied from 1 to 18 kPa. Hydrogel incubation with bovine serum albumin showed minimal protein adsorption. Finally, a cell cytotoxicity study of the precursor polymers with 3T3 fibroblasts demonstrated that the azide- and strained alkyne-functionalized PEGs are noncytotoxic. PMID- 26842781 TI - Molecular characterization of the Haemonchus contortus phosphoinositide-dependent protein kinase-1 gene (Hc-pdk-1). AB - BACKGROUND: Phosphoinositide-dependent protein kinase-1 (PDK-1), which functions downstream of phosphoinositide 3-kinase (AGE-1) and activates protein kinases of the AGC family, plays critical roles in regulating biology processes, such as metabolism, growth, development and survival. In the free-living nematode Caenorhabditis elegans, PDK-1 is a key component of the insulin-like signalling pathway, regulating the entry into and exit from dauer (arrested development). Although it is proposed that similar molecular mechanisms control the transition from the free-living to the parasitic stages of nematodes, nothing is known about PDK-1 in Haemonchus contortus, a socioeconomically important gastric nematode of ruminants. METHODS: Here, we isolated and characterized the pdk-1 gene (Hc-pdk-1) and its inferred product (Hc-PDK-1) from H. contortus. Using in vitro and in vivo methods, we then studied the transcriptional profiles of Hc-pdk-1 and anatomical gene expression patterns of Hc-PDK-1 in different developmental stages of C. elegans. RESULTS: In silico analysis of Hc-PDK-1 displayed conserved functional domains, such as protein kinase and pleckstrin homology (PH) domains and two predicted phosphorylation sites (Thr226/Tyr229), which are crucial for the phosphorylation of downstream signalling. The Hc-pdk-1 gene is transcribed in all of the main developmental stages of H. contortus, with its highest transcription in the infective third-stage larvae (iL3) compared with other stages. Transgene constructs, in which respective promoters were fused to the coding sequence for green fluorescent protein (GFP), were used to transform C. elegans, and to localize and compare the expression of Hc-pdk-1 and Ce-pdk-1. The expression of GFP under the control of the Hc-pdk-1 promoter was localized to the intestine, and head and tail neurons, contrasting somewhat the profile for the C. elegans ortholog, which is expressed in pharynx, intestine and head and tail neurons. CONCLUSIONS: This is the first characterization of pdk-1/PDK-1 from a trichostrongyloid nematode. Taken together, the findings from this study provide a first glimpse of the involvement of Hc-pdk-1 in the insulin-like signalling pathway in H. contortus. PMID- 26842784 TI - ESHG Plenary Debate 2015: Should Clinical Geneticists have their Genome Sequenced? PMID- 26842785 TI - Caldimicrobium thiodismutans sp. nov., a sulfur-disproportionating bacterium isolated from a hot spring, and emended description of the genus Caldimicrobium. AB - A novel autotrophic, thermophilic bacterium, strain TF1T, was isolated from a hot spring in Japan. Cells of strain TF1T were motile, Gram-stain-negative, rod shaped, 1.0-2.0 MUm in length and 0.5-0.6 MUm in width. Major components in the cellular fatty acid profile were C16:0, C18:0 and anteiso-C17:0. The temperature range for growth was 40-77 degrees C, and optimum temperature was 75 degrees C. The pH range for growth was 5.9-9.5, and the optimum pH was 7.5-8.8. Strain TF1T grew chemolithoautotrophically by disproportionation of sulfur, thiosulfate and sulfite. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain belongs to the family Thermodesulfobacteriaceae. The closest cultivated relative was Caldimicrobium rimae DST, with highest 16S rRNA gene sequence similarity of 96%. The genome of strain TF1T consists of one circular chromosome, with a size of 1.8 Mbp and G+C content of 38.30 mol%. On the basis of its phylogenetic and phenotypic properties, strain TF1T (=DSM 29380T=NBRC 110713T) is proposed as the type strain of a novel species, Caldimicrobium thiodismutans sp. nov. PMID- 26842786 TI - Extraordinary range expansion in a common bat: the potential roles of climate change and urbanisation. AB - Urbanisation and climate change are two global change processes that affect animal distributions, posing critical threats to biodiversity. Due to its versatile ecology and synurbic habits, Kuhl's pipistrelle (Pipistrellus kuhlii) offers a unique opportunity to explore the relative effects of climate change and urbanisation on species distributions. In a climate change scenario, this typically Mediterranean species is expected to expand its range in response to increasing temperatures. We collected 25,132 high-resolution occurrence records from P. kuhlii European range between 1980 and 2013 and modelled the species' distribution with a multi-temporal approach, using three bioclimatic variables and one proxy of urbanisation. Temperature in the coldest quarter of the year was the most important factor predicting the presence of P. kuhlii and showed an increasing trend in the study period; mean annual precipitation and precipitation seasonality were also relevant, but to a lower extent. Although urbanisation increased in recently colonised areas, it had little effect on the species' presence predictability. P. kuhlii expanded its geographical range by about 394 % in the last four decades, a process that can be interpreted as a response to climate change. PMID- 26842787 TI - Ornamentation, age, and survival of female striped plateau lizards, Sceloporus virgatus. AB - Individuals with greater expression of secondary sexual traits are often older and have higher survivorship than individuals with lower expression; if so, assessment of such indicator traits may provide genetic and/or direct benefits to potential mates. I examined the relationship between ornament expression, age, and survival in the striped plateau lizard, Sceloporus virgatus, a species with female-specific ornamentation that honestly signals reproductive quality. I followed a group of females from 2008 to 2013, examined ornament color and size as females aged, and compared ornamentation of survivors versus non-survivors. In addition, I explored whether other (non-ornamental) phenotypic characters predicted survival. I found that peak ornament expression (both color and size) of individual females changed year to year but appeared to be a weak signal of age due to high among-female variation in ornament expression that occurred independent of age and a non-linear pattern of change for ornament color. However, both absolute and relative ornament size did increase significantly as an individual aged and therefore may provide some age-related information such as reproductive investment, which is expected to increase as residual reproductive value declines with age. Individual survival was unrelated to peak ornament expression and to other phenotypic variables measured, providing no support for the ornament as a viability indicator and suggesting that individual survival prospects are affected by stochastic and environmental factors. PMID- 26842788 TI - Combined analysis of rearrangement of ALK, ROS1, somatic mutation of EGFR, KRAS, BRAF, PIK3CA, and mRNA expression of ERCC1, TYMS, RRM1, TUBB3, EGFR in patients with non-small cell lung cancer and their clinical significance. AB - PURPOSE: The assessment of single gene such as ERCC1, TYMS, RRM1, TUBB3, EGFR, KRAS, BRAF, PIK3CA, ALK, and ROS1 is now widely applied in therapeutic decisions of non-small cell lung cancer (NSCLC). The aim of our study was to concurrently analyze these genes and evaluate their clinical significance in patients with NSCLC. METHODS: Rearrangement of ALK and ROS1 was analyzed in 120 patients using FISH assays. Somatic mutation of EGFR, KRAS, BRAF, PIK3CA and mRNA expression of ERCC1, TYMS, RRM1, TUBB3, EGFR were examined by liquidchip platform in 350 patients . Data on clinical features were obtained from medical records of 119 patients, and the follow-up was conducted in 106 patients who received platinum based adjuvant chemotherapy. RESULTS: We identified 5.0% ALK rearrangements, 1.7% ROS1 rearrangements, 36.6% EGFR mutations, 8.9% KRAS mutations, 0% BRAF mutations, and 4.0% PIK3CA mutations. Double or coexisting mutations were identified in 13 patients. Significant correlations were observed among EGFR, KRAS mutation, ERCC1, TYMS, RRM1, TUBB3, EGFR expression, and clinical features, especially histology (P < 0.05). Significant cross-correlations were observed in some pairs of genes (P < 0.05). Patients with low RRM1 expression had a better progression-free survival (PFS) (P < 0.05). Furthermore, EGFR-mutated patients with low RRM1 expression or patients with both ERCC1 and RRM1 low expression had a better PFS (P < 0.05). CONCLUSION: Combined analysis of these commonly studied genes may promote the individual treatment in NSCLC. RRM1 may be a prognostic and predictive biomarker for PFS in patients with NSCLC who received platinum-based adjuvant chemotherapy, and combining EGFR mutation and RRM1 expression or combining ERCC1 and RRM1 expression can enhance prognostic and predictive power for PFS. PMID- 26842789 TI - Phase I/II study of nab-paclitaxel plus gemcitabine for chemotherapy-naive Japanese patients with metastatic pancreatic cancer. AB - PURPOSE: Efficacy and safety of nab-paclitaxel plus gemcitabine have not been clarified in Japanese patients with metastatic pancreatic cancer. No pharmacokinetic profile of co-administration of nab-paclitaxel and gemcitabine has been reported. We conducted a phase I/II study of the efficacy, safety, and pharmacokinetics in Japanese patients with metastatic pancreatic cancer. METHODS: The patients were administered 125 mg/m(2) nab-paclitaxel followed by 1000 mg/m(2) gemcitabine on day 1, 8, and 15 every 4 weeks. Treatment was continued until disease progression, unacceptable adverse events, or withdrawal of consent, whichever occurred first. The primary endpoints were tolerability in phase I and overall response rate according to RECIST in phase II. RESULTS: A total of 34 patients were enrolled. At the time of 1-year follow-up analysis since the last patient enrollment, the objective response rate by independent review committee was 58.8% (20 of 34 patients; 95% confidence interval [CI], 40.7-75.4%). The median progression-free survival and median overall survival were 6.5 months (95% CI, 5.1-8.3) and 13.5 months (95% CI, 10.6--not reached), respectively. Main adverse drug reactions of grade 3 or higher were neutropenia (70.6%), leukopenia (55.9%), anemia (14.7%), lymphocytopenia (14.7%), thrombocytopenia (14.7%), and peripheral sensory neuropathy (11.8%). There were no treatment-related deaths and no marked differences in pharmacokinetics of combined paclitaxel and gemcitabine in historical comparison between co-administration and monotherapies. CONCLUSIONS: Nab-paclitaxel plus gemcitabine regimen showed highly promising efficacy with manageable safety profile under careful observation and with appropriate supportive care in Japanese patients with metastatic pancreatic cancer. CLINICAL TRIAL NUMBER: JapicCTI-121987. PMID- 26842791 TI - Anomalous Inner-Gap Structure in Transport Characteristics of Superconducting Junctions with Degraded Interfaces. AB - Quantitative description of charge transport across tunneling and break-junction devices with novel superconductors encounters some problems not present or not as severe for traditional superconducting materials. In this work, we explain unexpected features in related transport characteristics as an effect of a degraded nanoscaled sheath at the superconductor surface. A model capturing the main aspects of the ballistic charge transport across hybrid superconducting structures with normally conducting nanometer-thick interlayers is proposed. The calculations are based on a scattering formalism taking into account Andreev electron-into-hole (and inverse) reflections at normal metal-superconductor interfaces as well as transmission and backscattering events in insulating barriers between the electrodes. Current-voltage characteristics of such devices exhibit a rich diversity of anomalous (from the viewpoint of the standard theory) features, in particular shift of differential-conductance maxima at gap voltages to lower positions and appearance of well-defined dips instead expected coherence peaks. We compare our results with related experimental data. PMID- 26842790 TI - Benefits of E-Cigarettes Among Heavy Smokers Undergoing a Lung Cancer Screening Program: Randomized Controlled Trial Protocol. AB - BACKGROUND: Smoking is a global public health problem. For this reason, experts have called smoking dependence a global epidemic. Over the past 5 years, sales of electronic cigarettes, or e-cigarettes, have been growing strongly in many countries. Yet there is only partial evidence that e-cigarettes are beneficial for smoking cessation. In particular, although it has been proven that nicotine replacement devices may help individuals stop smoking and tolerate withdrawal symptoms, e-cigarettes' power to increase the quitting success rate is still limited, ranging from 5% to 20% dependent on smokers' baseline conditions as shown by a recent Cochrane review. Consequently, it is urgent to know if e cigarettes may have a higher success rate than other nicotine replacement methods and under what conditions. Furthermore, the effects of the therapeutic setting and the relationship between individual characteristics and the success rate have not been tested. This protocol is particularly innovative, because it aims to test the effectiveness of electronic devices in a screening program (the COSMOS II lung cancer prevention program at the European Institute of Oncology), where tobacco reduction is needed to lower individuals' lung cancer risks. OBJECTIVE: This protocol was designed with the primary aim of investigating the role of tobacco-free cigarettes in helping smokers improve lung health and either quit smoking or reduce their tobacco consumption. In particular, we aim to investigate the impact of a 3-month e-cigarettes program to reduce smoking-related respiratory symptoms (eg, dry cough, shortness of breath, mouth irritation, and phlegm) through reduced consumption of tobacco cigarettes. Furthermore, we evaluate the behavioral and psychological (eg, well-being, mood, and quality of life) effects of the treatment. METHODS: This is a prospective, randomized, placebo-controlled, double-blind, three-parallel group study. The study is organized as a nested randomized controlled study with 3 branches: a nicotine e cigarettes group, a nicotine-free e-cigarettes group, and a control group. The study is nested in a screening program for early lung cancer detection in heavy smokers. RESULTS: The study is open and is still recruiting. CONCLUSIONS: Stopping or reducing tobacco consumption should be a main goal of any health organization. However, traditional antismoking programs are expensive and not always effective. Therefore, favoring a partial or complete shift to e-cigarettes in heavy smokers (eg, persons at high risk for a number of diseases) could be considered a moral imperative. However, before following this path, sound and reliable data on large samples and in a variety of contexts are required. TRIAL REGISTRATION: Clinicaltrials.gov NCT02422914; https://clinicaltrials.gov/ct2/show/NCT02422914 (Archived by WebCite at http://www.webcitation.org/6etwz1bPL). PMID- 26842792 TI - Development of Silicalite/Glucose Oxidase-Based Biosensor and Its Application for Glucose Determination in Juices and Nectars. AB - The application of silicalite for improvement of enzyme adsorption on new stainless steel electrodes is reported. Glucose oxidase (GOx) was immobilized by two methods: cross-linking by glutaraldehyde (GOx-GA) and cross-linking by glutaraldehyde along with GOx adsorption on silicalite-modified electrode (SME) (GOx-SME-GA). The GOx-SME-GA biosensors were characterized by a four- to fivefold higher sensitivity than GOx-GA biosensor. It was concluded that silicalite together with GA sufficiently enhances enzyme adhesion on stainless steel electrodes. The developed GOx-SME-GA biosensors were characterized by good reproducibility of biosensor preparation (relative standard deviation (RSD)-18 %), improved signal reproducibility (RSD of glucose determination was 7 %), and good storage stability (29 % loss of activity after 18-day storage). A series of fruit juices and nectars was analyzed using GOx-SME-GA biosensor for determination of glucose concentration. The obtained results showed good correlation with the data of high-performance liquid chromatography (HPLC) (R = 0.99). PMID- 26842793 TI - Enhanced Photocatalytic Activity of the Carbon Quantum Dot-Modified BiOI Microsphere. AB - Novel carbon quantum dot (CQD)-modified BiOI photocatalysts were prepared via a facile hydrothermal process. The CQD-modified BiOI materials were characterized by multiple techniques. The CQD with an average size around several nanometers was distributed on the surface of BiOI microsphere. Its photocatalytic activity was investigated sufficiently by the photodegradation of methylene orange (MO). The results showed that the CQD/BiOI 1.5 wt.% sample exhibited the optimum photocatalytic activity, which was 2.5 times that of the pure BiOI. This improvement was attributed to the crucial role of CQDs, which could be acted as a photocenter for absorbing solar light, charge separation center for suppressing charge recombination. PMID- 26842794 TI - Magneto-Sensitive Adsorbents Modified by Functional Nitrogen-Containing Groups. AB - In order to obtain amino-functionalized silica materials with magnetic core, one step synthesis was carried out. Several materials, differ in number and structure of amino groups, were synthesized on the basis of sol-gel method. The synthesized materials were examined by several analytical techniques. The presence and content of amino groups were measured by using Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy and acid-base titration, respectively. Specific surface areas were measured by nitrogen/adsorption desorption isotherms. It was proved that sol-gel approach leads to obtain materials with high content of amino groups built into their surfaces (in the range 1.6-2.7 mmol/g). As obtained materials were tested as potential adsorbents for copper(II) ions. The received maximum adsorption capacities were in the range 0.4-0.7 mmol/g. PMID- 26842796 TI - Oxygen Effects on Performance of Electrically Bistable Devices Based on Hybrid Silver Sulfide Poly(N-vinylcarbazole) Nanocomposites. AB - An organic/inorganic bistable device is fabricated by using a simple spin-coating technique, in which the hybrid silver sulfide (Ag2S) poly(N-vinylcarbazole) (PVK) nanocomposite film is sandwiched between two electrodes. An obvious electrical hysteresis is observed in the current-voltage (I-V) curve of the device measured in the presence of different oxygen concentrations, and the magnitude of the electrical hysteresis is decreased with a decrease of the oxygen concentrations. The electrical bistability of the device exhibits a strong dependence on the oxygen concentrations, and the current variation of the OFF state is higher than that of the ON state with the gas atmosphere changing from N2 to air. Different theoretical models have been employed to describe the carrier transport mechanisms of the device in the OFF and ON states measured in different gas atmospheres on the basis of the experimental I-V results, and the carrier transport of the device in the ON state measured in air is very different from that measured in N2 and low O2 concentrations due to the participation of oxygen vacancies in the trapping and de-trapping processes of electrons into and out of the Ag2S/PVK heterointerface. PMID- 26842795 TI - Simultaneous Quantitative Detection of Helicobacter Pylori Based on a Rapid and Sensitive Testing Platform using Quantum Dots-Labeled Immunochromatiographic Test Strips. AB - Quantum dots-labeled urea-enzyme antibody-based rapid immunochromatographic test strips have been developed as quantitative fluorescence point-of-care tests (POCTs) to detect helicobacter pylori. Presented in this study is a new test strip reader designed to run on tablet personal computers (PCs), which is portable for outdoor detection even without an alternating current (AC) power supply. A Wi-Fi module was integrated into the reader to improve its portability. Patient information was loaded by a barcode scanner, and an application designed to run on tablet PCs was developed to handle the acquired images. A vision algorithm called Kmeans was used for picture processing. Different concentrations of various human blood samples were tested to evaluate the stability and accuracy of the fabricated device. Results demonstrate that the reader can provide an easy, rapid, simultaneous, quantitative detection for helicobacter pylori. The proposed test strip reader has a lighter weight than existing detection readers, and it can run for long durations without an AC power supply, thus verifying that it possesses advantages for outdoor detection. Given its fast detection speed and high accuracy, the proposed reader combined with quantum dots-labeled test strips is suitable for POCTs and owns great potential in applications such as screening patients with infection of helicobacter pylori, etc. in near future. PMID- 26842797 TI - Preparation and Application of Electrodes in Capacitive Deionization (CDI): a State-of-Art Review. AB - As a promising desalination technology, capacitive deionization (CDI) have shown practicality and cost-effectiveness in brackish water treatment. Developing more efficient electrode materials is the key to improving salt removal performance. This work reviewed current progress on electrode fabrication in application of CDI. Fundamental principal (e.g. EDL theory and adsorption isotherms) and process factors (e.g. pore distribution, potential, salt type and concentration) of CDI performance were presented first. It was then followed by in-depth discussion and comparison on properties and fabrication technique of different electrodes, including carbon aerogel, activated carbon, carbon nanotubes, graphene and ordered mesoporous carbon. Finally, polyaniline as conductive polymer and its potential application as CDI electrode-enhancing materials were also discussed. PMID- 26842798 TI - Integration of flow studies for robust selection of mechanoresponsive genes. AB - Blood flow is an essential contributor to plaque growth, composition and initiation. It is sensed by endothelial cells, which react to blood flow by expressing > 1000 genes. The sheer number of genes implies that one needs genomic techniques to unravel their response in disease. Individual genomic studies have been performed but lack sufficient power to identify subtle changes in gene expression. In this study, we investigated whether a systematic meta-analysis of available microarray studies can improve their consistency. We identified 17 studies using microarrays, of which six were performed in vivo and 11 in vitro. The in vivo studies were disregarded due to the lack of the shear profile. Of the in vitro studies, a cross-platform integration of human studies (HUVECs in flow cells) showed high concordance (> 90 %). The human data set identified > 1600 genes to be shear responsive, more than any other study and in this gene set all known mechanosensitive genes and pathways were present. A detailed network analysis indicated a power distribution (e. g. the presence of hubs), without a hierarchical organisation. The average cluster coefficient was high and further analysis indicated an aggregation of 3 and 4 element motifs, indicating a high prevalence of feedback and feed forward loops, similar to prokaryotic cells. In conclusion, this initial study presented a novel method to integrate human-based mechanosensitive studies to increase its power. The robust network was large, contained all known mechanosensitive pathways and its structure revealed hubs, and a large aggregate of feedback and feed forward loops. PMID- 26842800 TI - The Localization of Phenolic Compounds in Liposomal Bilayers and Their Effects on Surface Characteristics and Colloidal Stability. AB - The interactions with and effects of five chemically distinct, bioactive phenolic compounds on the lipid bilayers of model dipalmitoylphosphatidylcholine (DPPC) liposomes were investigated. Complementary analytical techniques, including differential scanning calorimetry (DSC) and phosphorus and proton nuclear magnetic resonance spectroscopy (NMR), were employed in order to determine the location of the compounds within the bilayer and to correlate location with their effects on bilayer characteristics and liposomal stability. As compared to the phenolic compounds localized in the glycerol region of the DPPC head group within the bilayer, which enhanced the colloidal stability of the liposomes, compounds located closer to the center of the bilayer reduced vesicle stability as a function of time. Molecules present in the upper region of liposomal DPPC acyl chains (C1-C10) inhibited liposomal aggregation and size increase, perhaps due to tighter packing of adjoining DPPC molecules and increased surface exposure of DPPC phosphate head groups. These data may be useful for designing liposomal systems containing hydrophobic phenols and other small molecules, selecting appropriate analytical methods for determining their location within liposomal bilayers, and predicting their effects on liposome characteristics early in the liposome formulation development process. PMID- 26842799 TI - Is plasticity within the retrotrapezoid nucleus responsible for the recovery of the PCO2 set-point after carotid body denervation in rats? AB - KEY POINTS: Arterial PCO2 is kept constant via breathing adjustments elicited, at least partly, by central chemoreceptors (CCRs) and the carotid bodies (CBs). The CBs may be active in a normal oxygen environment because their removal reduces breathing. Thereafter, breathing slowly returns to normal. In the present study, we investigated whether an increase in the activity of CCRs accounts for this return. One week after CB excision, the hypoxic ventilatory reflex was greatly reduced as expected, whereas ventilation and blood gases at rest under normoxia were normal. Optogenetic inhibition of Phox2b-expressing neurons including the retrotrapezoid nucleus, a cluster of CCRs, reduced breathing proportionally to arterial pH. The hypopnoea was greater after CB excision but only in a normal or hypoxic environment. The difference could be simply explained by the loss of fast feedback from the CBs. We conclude that, in rats, CB denervation may not produce CCR plasticity. We also question whether the transient hypoventilation elicited by CB denervation means that these afferents are active under normoxia. ABSTRACT: Carotid body denervation (CBD) causes hypoventilation and increases the arterial PCO2 set-point; these effects eventually subside. The hypoventilation is attributed to reduced CB afferent activity and the PCO2 set-point recovery to CNS plasticity. In the present study, we investigated whether the retrotrapezoid nucleus (RTN), a group of non-catecholaminergic Phox2b-expressing central respiratory chemoreceptors (CCRs), is the site of such plasticity. We evaluated the contribution of the RTN to breathing frequency (FR ), tidal volume (VT ) and minute volume (VE ) by inhibiting this nucleus optogenetically for 10 s (archaerhodopsinT3.0) in unanaesthetized rats breathing various levels of O2 and/or CO2 . The measurements were made in seven rats before and 6-7 days after CBD and were repeated in seven sham-operated rats. Seven days post-CBD, blood gases and ventilation in 21% O2 were normal, whereas the hypoxic ventilatory reflex was still depressed (95.3%) and hypoxia no longer evoked sighs. Sham surgery had no effect. In normoxia or hypoxia, RTN inhibition produced a more sustained hypopnoea post-CBD than before; in hyperoxia, the responses were identical. Post-CBD, RTN inhibition reduced FR and VE in proportion to arterial pH or PCO2 (DeltaVE : 3.3 +/- 1.5% resting VE /0.01 pHa). In these rats, 20.7 +/- 8.9% of RTN neurons expressed archaerhodopsinT3.0. Hypercapnia (3-6% FiCO2 ) increased FR and VT in CBD rats (n = 4). In conclusion, RTN regulates FR and VE in a pH-dependent manner after CBD, consistent with its postulated CCR function. RTN inhibition produces a more sustained hypopnoea after CBD than before, although this change may simply result from the loss of the fast feedback action of the CBs. PMID- 26842801 TI - Cellular delivery and photochemical release of a caged inositol-pyrophosphate induces PH-domain translocation in cellulo. AB - Inositol pyrophosphates, such as diphospho-myo-inositol pentakisphosphates (InsP7), are an important family of signalling molecules, implicated in many cellular processes and therapeutic indications including insulin secretion, glucose homeostasis and weight gain. To understand their cellular functions, chemical tools such as photocaged analogues for their real-time modulation in cells are required. Here we describe a concise, modular synthesis of InsP7 and caged InsP7. The caged molecule is stable and releases InsP7 only on irradiation. While photocaged InsP7 does not enter cells, its cellular uptake is achieved using nanoparticles formed by association with a guanidinium-rich molecular transporter. This novel synthesis and unprecedented polyphosphate delivery strategy enable the first studies required to understand InsP7 signalling in cells with controlled spatiotemporal resolution. It is shown herein that cytoplasmic photouncaging of InsP7 leads to translocation of the PH-domain of Akt, an important signalling-node kinase involved in glucose homeostasis, from the membrane into the cytoplasm. PMID- 26842802 TI - HIF-2alpha promotes epithelial-mesenchymal transition through regulating Twist2 binding to the promoter of E-cadherin in pancreatic cancer. AB - BACKGROUND: Epithelial-mesenchymal transition (EMT) is a dedifferentiation process that mainly involves in mesenchymal marker upregulation, epithelial maker downregulation and cell polarity loss. Related hypoxia factors play a crucial role in EMT, however, it remains few evidence to clarify the role of HIF-2alpha in EMT in pancreatic cancer. METHOD: In this study, we investigated the expression of HIF-2alpha and E-cadherin by immunohistochemistry in 70 pancreatic cancer patients, as well as the correlation to the clinicopathologic characteristics. Then we regulated the expression of HIF-2alpha in pancreatic cancer cells to examine the role of HIF-2alpha on invasion and migration in vitro. Finally, we tested the relation of HIF-2alpha and EMT related proteins by Western blot and determined whether HIF-2alpha regulated EMT through Twist regulating the expression of E-cadherin by Chromatin immunoprecipitation (ChIP) assay. RESULTS: We found that HIF-2alpha protein was expressed positively in 67.1% (47/70) of pancreatic cancer tissues and 11.4% (8/70) of adjacent non-tumor pancreatic tissues, and there was a significant difference in the positive rate of HIF-2alpha protein between two groups (chi2 = 45.549, P < 0.05). In addition, the staining for HIF-2alpha was correlated with tumor differentiation (P < 0.05), clinical stage (P < 0.05) and lymph node metastasis (P < 0.05), while E-cadherin expression was only correlated with lymph node metastasis (P < 0.05). HIF-2alpha promoted cell migration, invasion in vitro, and regulated the expression of E cadherin and MMPs, which are critical to EMT. Our further ChIP assay suggested that only Twist2 could bind to the promoter of E-cadherin in -714 bp region site, but there is no positive binding capacity in -295 bp promoter region site of E cadherin. Clinical tissues IHC staining showed that Twist2 and E-cadherin expression had an obviously negative correlation in pancreatic cancer. Nevertheless, it had no obvious correlation between Twist1 and E-cadherin. CONCLUSION: These findings indicated that HIF-2alpha promotes EMT in pancreatic cancer by regulating Twist2 binding to the promoter of E-cadherin, which meant that HIF-2alpha and this pathway may be effective therapeutic targets for pancreatic cancer. PMID- 26842803 TI - Noise induced hearing loss impairs spatial learning/memory and hippocampal neurogenesis in mice. AB - Hearing loss has been associated with cognitive decline in the elderly and is considered to be an independent risk factor for dementia. One of the most common causes for acquired sensorineural hearing loss is exposure to excessive noise, which has been found to impair learning ability and cognitive performance in human subjects and animal models. Noise exposure has also been found to depress neurogenesis in the hippocampus. However, the effect is mainly attributed to the oxidant stress of noise on the cognitive brain. In the present study, young adult CBA/CAJ mice (between 1.5 and 2 months of age) were briefly exposed a high sound level to produce moderate-to-severe hearing loss. In both the blood and hippocampus, only transient oxidative stress was observed after noise exposure. However, a deficit in spatial learning/memory was revealed 3 months after noise exposure. Moreover, the deficit was correlated with the degree of hearing loss and was associated with a decrease in neurogenesis in the hippocampus. We believe that the observed effects were likely due to hearing loss rather than the initial oxidant stress, which only lasted for a short period of time. PMID- 26842804 TI - Design, Synthesis and Biological Evaluation of Novel Rapamycin Benzothiazole Hybrids as mTOR Targeted Anti-cancer Agents. AB - The immunosuppressant drug rapamycin, was firstly identified as a mammalian target of rapamycin (mTOR) allosteric inhibitor, and its derivatives have been successfully developed as anti-cancer drugs. Therefore, finding rapamycin derivatives with better anti-cancer activity has been proved to be an effective way to discover new targeted anti-cancer drugs. In this paper, structure modification was performed at the C-43 position of rapamycin using bioisosterism and a hybrid approach: a series of novel rapamycin-benzothiazole hybrids 4a-e, 5a c, and 9a, b have been designed, synthesized and evaluated for their anti-cancer activity against Caski, CNE-2, SGC-7901, PC-3, SK-NEP-1 and A-375 human cancer cell lines. Some of these compounds (4a-e, 9a, b) displayed good to excellent potency against the Caski and SK-NEP-1 cell line as compared with rapamycin. Compound 9b as the most active compound showed IC50 values of 8.3 (Caski) and 9.6 MUM (SK-NEP-1), respectively. In addition, research on the mechanism showed that 9b was able to cause G1 phase arrest and induce apoptosis in the Caski cell line. Most importantly, it significantly decreased the phosphorylation of S6 ribosomal protein, p70S6K1 and 4EBP1, which indicated that 9b inhibited the cancer cell growth by blocking the mTOR pathway and may have the potential to become a new mTOR inhibitor. PMID- 26842805 TI - Obesity Prevention Programs in Children: Impact on Weight, Shape and Food Concern. AB - Childhood overweight and obesity have an estimated prevalence of 10 % globally. High body mass index (BMI) is a known major predictor of body dissatisfaction, problem eating, low self-esteem, bullying and poor social and health outcomes for children. Childhood is also a time when lifelong habits are established, and as such is a time where prevention efforts have a high chance of success if implemented appropriately. Obesity prevention in children also has the potential to create weight, shape and food concerns in children and as such programs should focus on the principle first, do no harm. This paper canvasses existing literature and intervention program data to make the following recommendations for effective childhood obesity prevention: Programs should be educative for both children and their parents, programs should be inclusive of the whole family, there should be a focus on health and growth, not weight, and parents, schools and children should all be involved. PMID- 26842808 TI - A one-step synthesis of hollow periodic mesoporous organosilica spheres with radially oriented mesochannels. AB - A simple and effective one-step method is proposed for the fabrication of hollow periodic mesoporous organosilica spheres (HPMOSs). The obtained HPMOSs possess well-defined spherical morphology, uniform and tunable particle size, adjustable hollow void structure, and radially oriented mesochannels in their shells. PMID- 26842809 TI - Effect of Trap Color, Height, and Orientation on the Capture of Yellow and Stick Tea Thrips (Thysanoptera: Thripidae) and Nontarget Insects in Tea Gardens. AB - Two thrips species-the yellow tea thrips (Scirtothrips dorsalis Hood) and the stick tea thrips (Dendrothrips minowai Priesner)-are serious pests affecting tea plants in southern China. Although the stick tea thrips is primarily restricted to southern China, the yellow tea thrips is gradually proliferating worldwide. Colored sticky card traps may be useful for monitoring and capturing these species, but a systematic analysis has not been conducted to identify the most effective trap color, height, and orientation. We performed indoor experiments using an orthogonal experimental design, as well as field tests in tea gardens, to identify the color most attractive to the two thrips species. Field tests were then conducted using color-optimized traps-lawngreen (RGB: 124, 252, 0) for yellow thrips and lime (RGB: 0, 255, 0) for stick tea thrips-to determine the most effective trap height and orientation. The greatest numbers of both yellow and stick tea thrips were captured on traps positioned 0-20 cm above the tea canopy in an east-west orientation. We also evaluated the performance of the color-optimized sticky card traps compared with commercially available yellow ones. Significantly more yellow and stick tea thrips and fewer natural enemies were captured on the color-optimized traps than on commercial ones. Although additional research is needed to explain the responses of the two different species and to increase trap effectiveness, our findings should assist in the control of these harmful insects. PMID- 26842807 TI - Precocious leaf senescence by functional loss of PROTEIN S-ACYL TRANSFERASE14 involves the NPR1-dependent salicylic acid signaling. AB - We report here that Arabidopsis PROTEIN S-ACYL TRANSFERASE14 (PAT14), through its palmitate transferase activity, acts at the vacuolar trafficking route to repress salicylic acid (SA) signaling, thus mediating age-dependent but not carbon starvation-induced leaf senescence. Functional loss of PAT14 resulted in precocious leaf senescence and its transcriptomic analysis revealed that senescence was dependent on salicylic acid. Overexpressing PAT14 suppressed the expression of SA responsive genes. Introducing the SA deficient mutants, npr1-5 and NahG, but not other hormonal mutants, completely suppressed the precocious leaf senescence of PAT14 loss-of-function, further supporting the epistatic relation between PAT14 and the SA pathway. By confocal fluorescence microscopy, we showed that PAT14 is localized at the Golgi, the trans-Golg network/early endosome, and prevacuolar compartments, indicating its roles through vacuolar trafficking. By reporter analysis and real time PCRs, we showed that the expression PAT14, unlike most of the senescence associated genes, is not developmentally regulated, suggesting post-transcriptional regulatory mechanisms on its functionality. We further showed that the maize and wheat homologs of PAT14 fully rescued the precocious leaf senescence of pat14-2, demonstrating that the role of PAT14 in suppressing SA signaling during age-dependent leaf senescence is evolutionarily conserved between dicots and monocots. PMID- 26842810 TI - A diagenetic control on the Early Triassic Smithian-Spathian carbon isotopic excursions recorded in the marine settings of the Thaynes Group (Utah, USA). AB - In the aftermath of the end-Permian mass extinction, Early Triassic sediments record some of the largest Phanerozoic carbon isotopic excursions. Among them, a global Smithian-negative carbonate carbon isotope excursion has been identified, followed by an abrupt increase across the Smithian-Spathian boundary (SSB; ~250.8 Myr ago). This chemostratigraphic evolution is associated with palaeontological evidence that indicate a major collapse of terrestrial and marine ecosystems during the Late Smithian. It is commonly assumed that Smithian and Spathian isotopic variations are intimately linked to major perturbations in the exogenic carbon reservoir. We present paired carbon isotopes measurements from the Thaynes Group (Utah, USA) to evaluate the extent to which the Early Triassic isotopic perturbations reflect changes in the exogenic carbon cycle. The delta(13) Ccarb variations obtained here reproduce the known Smithian delta(13) Ccarb -negative excursion. However, the delta(13) C signal of the bulk organic matter is invariant across the SSB and variations in the delta(34) S signal of sedimentary sulphides are interpreted here to reflect the intensity of sediment remobilization. We argue that Middle to Late Smithian delta(13) Ccarb signal in the shallow marine environments of the Thaynes Group does not reflect secular evolution of the exogenic carbon cycle but rather physicochemical conditions at the sediment-water interface leading to authigenic carbonate formation during early diagenetic processes. PMID- 26842812 TI - MACEs Not Associated With the Use of Biologic Therapy for Psoriasis in Real-World Clinical Practice: A Canadian Multicenter Retrospective Study. AB - INTRODUCTION: Previous reports have shown inconsistent findings with regard to the relationship between biologic therapy and risk for major adverse cardiovascular events (MACEs). OBJECTIVES: The aim of this study was to determine the overall rate of MACEs in a cohort of 398 patients. METHODS: All patients treated with biologics for psoriasis at 2 academic centers in Toronto, Ontario, between September 2005 and September 2014 were considered for inclusion. Medical records were reviewed to identify MACEs. RESULTS: A total of 398 patients were included. The median duration of disease was 19.8 years. Median time to biologic therapy withdrawal because of an adverse event was 23.5 months. In this cohort, no MACEs were identified in patients treated with biologic therapy. CONCLUSIONS: Biologic treatment for psoriasis was not associated with increased cardiovascular risk in this cohort. These results require validation in larger studies. PMID- 26842813 TI - Bile Duct Hamartoma Mimicking Metastatic Cholangiocarcinoma. PMID- 26842811 TI - High-throughput sequencing reveals the core gut microbiome of Bar-headed goose (Anser indicus) in different wintering areas in Tibet. AB - Elucidating the spatial dynamic and core gut microbiome related to wild bar headed goose is of crucial importance for probiotics development that may meet the demands of bar-headed goose artificial breeding industries and accelerate the domestication of this species. However, the core microbial communities in the wild bar-headed geese remain totally unknown. Here, for the first time, we present a comprehensive survey of bar-headed geese gut microbial communities by Illumina high-throughput sequencing technology using nine individuals from three distinct wintering locations in Tibet. A total of 236,676 sequences were analyzed, and 607 OTUs were identified. We show that the gut microbial communities of bar-headed geese have representatives of 14 phyla and are dominated by Firmicutes, Proteobacteria, Actinobacteria, and Bacteroidetes. The additive abundance of these four most dominant phyla was above 96% across all the samples. At the genus level, the sequences represented 150 genera. A set of 19 genera were present in all samples and considered as core gut microbiome. The top seven most abundant core genera were distributed in that four dominant phyla. Among them, four genera (Lactococcus, Bacillus, Solibacillus, and Streptococcus) belonged to Firmicutes, while for other three phyla, each containing one genus, such as Proteobacteria (genus Pseudomonas), Actinobacteria (genus Arthrobacter), and Bacteroidetes (genus Bacteroides). This broad survey represents the most in depth assessment, to date, of the gut microbes that associated with bar-headed geese. These data create a baseline for future bar-headed goose microbiology research, and make an original contribution to probiotics development for bar headed goose artificial breeding industries. PMID- 26842814 TI - Decline in intertidal biota after the 2011 Great East Japan Earthquake and Tsunami and the Fukushima nuclear disaster: field observations. AB - In 2011, 2012, and 2013, in the intertidal zones of eastern Japan, we investigated the ecological effects of the severe accident at the Fukushima Daiichi Nuclear Power Plant that accompanied the 2011 Great East Japan Earthquake and Tsunami. The number of intertidal species decreased significantly with decreasing distance from the power plant, and no rock shell (Thais clavigera) specimens were collected near the plant, from Hirono to Futaba Beach (a distance of approximately 30 km) in 2012. The collection of rock shell specimens at many other sites hit by the tsunami suggests that the absence of rock shells around the plant in 2012 might have been caused by the nuclear accident in 2011. Quantitative surveys in 2013 showed that the number of species and population densities in the intertidal zones were much lower at sites near, or within several kilometers south of, the plant than at other sites and lower than in 1995, especially in the case of Arthropoda. There is no clear explanation for these findings, but it is evident that the intertidal biota around the power plant has been affected since the nuclear accident. PMID- 26842815 TI - An Innovative Educational Program for International Hematopoietic Cell Transplant Pediatric Patients. AB - Pediatric patients and their families confront a difficult journey with hematopoietic cell transplantation. Understanding complex information, navigation, and coping with emotional, physical, and social changes in the patient, parents and family nucleus life could be quite challenging for all. In Spanish-speaking countries where transplant is emerging as an available treatment option, healthcare professionals encounter the lack or limited quality resources to educate pediatric patients and their families on a complex treatment process. Also, the level of literacy of each family varies widely, making transplant education very difficult to address in a simple and engaging way that could benefit all levels of literacy and foster well-being in the family as a whole, so they are prepared to make better informed decisions and decrease stress in all members. Super Sam versus the Marrow Monsters is a DVD resource made by the National Marrow Donor Program(r) (NMDP)/Be The Match(r) intended as an educational tool, to be shared with our U.S. network transplant centers to use when educating their pediatric patients. Hospital Angeles Lomas in the State of Mexico-member of the NMDP international network-has adopted the DVD with their pediatric audience, with very successful results, and demonstrates the benefits of expanding the initial intended use. PMID- 26842816 TI - Prostate Cancer Knowledge, Prevention, and Screening Behaviors in Jamaican Men. AB - Screening is the only effective method of reducing prostate cancer mortality. Several reports have documented poor prostate cancer awareness and screening practices in Jamaican men. The Jamaica Cancer Society provides the most organized and largest form of screening in Jamaica and hosts an annual mass screening clinic on Prostate Cancer Awareness Day in September. We sought to determine the knowledge and attitudes towards screening and risks and prevention of prostate cancer. The study represented a cross-sectional analysis of 55 men presenting for screening on Prostate Cancer Awareness Day, September 2014 in Kingston, Jamaica. Information on prostate cancer knowledge and attitudes towards screening was obtained using interviewer-administered questionnaires (The Integrative Model of Prostate Cancer Disparity (PIPCaD). Prostate specific antigen (PSA) and digital rectal examination (DRE) were obtained from all patients. Mean PSA of participating men was 1.5 +/- 1.48 ng/ml. Fifteen percent of men surveyed had a family history of prostate cancer. Prostate cancer knowledge was moderate, with at least 84 % of men responding correctly to 5 of 10 questions referring to prostate cancer risk and prevention. Most men had a favorable attitude towards screening. Starch formed the major portion of the diet in 68 % of men and 35 % of men engaged in no physical activity. Jamaican men surveyed have moderate prostate cancer knowledge and a positive attitude towards screening and prostate cancer prevention activities. However, the application of activities for potential prevention of modifiable risk factors is poor. PMID- 26842817 TI - Craniospinal irradiation with concomitant and adjuvant temozolomide--a feasibility assessment of toxicity in patients with glioblastoma with a PNET component. AB - There is no standard treatment for glioblastoma with elements of PNET (GBM-PNET). Conventional treatment for glioblastoma is surgery followed by focal radiotherapy with concurrent temozolomide. Given the increased propensity for neuroaxial metastases seen with GBM-PNETs, craniospinal irradiation (CSI) with temozolomide (TMZ) could be a feasible treatment option but little is known regarding its toxicity. The clinical records of all patients treated at two UK neuro-oncology centres with concurrent CSI and TMZ were examined for details of surgery, radiotherapy, chemotherapy and toxicities related to the CSI-TMZ component of their treatment. Eight patients were treated with CSI-TMZ, the majority (6/8) for GBM-PNET. All patients completed radiotherapy to the craniospinal axis 35-40 Gy in 20-24 daily fractions with a focal boost to the tumour of 14-23.4 Gy in 8-13 daily fractions. Concurrent TMZ was administered at 75 mg/m(2) for seven of the cohort, with the other patient receiving 50 mg/m(2). The most commonly observed non-haematological toxicities were nausea and vomiting, with all patients experiencing at least grade 2 symptoms of either or both. All patients had at least grade 3 lymphopaenia. Two patients experience grade 4 neutropaenia and grade 3 thrombocytopaenia. Three of the eight patients required omission of TMZ for part of their chemoradiotherapy and 3/8 required hospital admission at some point during chemoradiotherapy. The addition of TMZ to CSI did not interrupt radiotherapy. Principal toxicities were neutropaenia, lymphopaenia, thrombocytopaenia, nausea and vomiting. Treatment with CSI-TMZ merits further investigation and may be suitable for patients with tumours at high-risk of metastatic spread throughout the CNS who have TMZ-sensitive pathologies. PMID- 26842818 TI - Advances in HSP27 and HSP90-targeting strategies for glioblastoma. AB - Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. There is a critical need for novel strategies to abolish the molecular mechanisms that support GBM growth, invasion and treatment resistance. The heat shock proteins, HSP27 and HSP90, serve these pivotal roles in tumor cells and have been identified as effective targets for developing therapeutics. Natural and synthetic inhibitors have been evaluated in clinical trials for several forms of systemic cancer but none as yet for GBM. This topic review summarizes the current preclinical evidence and rationale to define the potential of HSP27 and HSP90 inhibitors in GBM management. PMID- 26842820 TI - Analysis of serum transthyretin by on-line immunoaffinity solid-phase extraction capillary electrophoresis mass spectrometry using magnetic beads. AB - In this paper, an on-line immunoaffinity solid-phase extraction capillary electrophoresis mass spectrometry (IA-SPE-CE-MS) method using magnetic beads (MBs) is described for the analysis of serum transthyretin (TTR), which is a protein related to different types of amyloidosis. First, purification of TTR from serum was investigated by off-line immunoprecipitation and CE-MS. The suitability of three Protein A (ProA) MBs (Protein A Ultrarapid Agarose(TM) (UAPA), Dynabeads((r)) Protein A (DyPA) and SiMAG-Protein A (SiPA) and AffiAmino Ultrarapid Agarose(TM) (UAAF) MBs to prepare an IA sorbent with a polyclonal antibody (Ab) against TTR, was studied. In all cases, results were repeatable and it was possible the identification and the quantitation of the relative abundance of the six most abundant TTR proteoforms. Although recoveries were the best with UAPA MBs, UAAF MBs were preferred for on-line immunopurification because Ab was not eluted from the MBs. Under the optimized conditions with standards in IA-SPE CE-MS, microcartridge lifetime (>20 analyses/day) and repeatability (2.9 and 4.3% RSD for migration times and peak areas) were good, the method was linear between 5 and 25 MUg/mL and LOD was around 1 MUg/mL (25 times lower than by CE-MS, ~25 MUg/mL). A simple off-line sample pretreatment based on precipitation of the most abundant proteins with 5% (v/v) of phenol was necessary to clean-up serum samples. The potential of the on-line method to screen for familial amyloidotic polyneuropathy type I (FAP-I), which is the most common hereditary systemic amyloidosis, was demonstrated analysing serum samples from healthy controls and FAP-I patients. PMID- 26842821 TI - App helps to improve contraception uptake in rural India. PMID- 26842819 TI - Discovery of the youngest sex chromosomes reveals first case of convergent co option of ancestral autosomes in turtles. AB - Most turtle species possess temperature-dependent sex determination (TSD), but genotypic sex determination (GSD) has evolved multiple times independently from the TSD ancestral condition. GSD in animals typically involves sex chromosomes, yet the sex chromosome system of only 9 out of 18 known GSD turtles has been characterized. Here, we combine comparative genome hybridization (CGH) and BAC clone fluorescent in situ hybridization (BAC FISH) to identify a macro-chromosome XX/XY system in the GSD wood turtle Glyptemys insculpta (GIN), the youngest known sex chromosomes in chelonians (8-20 My old). Comparative analyses show that GIN X/Y is homologous to chromosome 4 of Chrysemys picta (CPI) painted turtles, chromosome 5 of Gallus gallus chicken, and thus to the X/Y sex chromosomes of Siebenrockiella crassicollis black marsh turtles. We tentatively assign the gene content of the mapped BACs from CPI chromosome 4 (CPI-4) to GIN-X/Y. Chromosomal rearrangements were detected in G. insculpta sex chromosome pair that co-localize with the male-specific region of GIN-Y and encompass a gene involved in sexual development (Wt1-a putative master gene in TSD turtles). Such inversions may have mediated the divergence of G. insculpta sex chromosome pair and facilitated GSD evolution in this turtle. Our results illuminate the structure, origin, and evolution of sex chromosomes in G. insculpta and reveal the first case of convergent co-option of an autosomal pair as sex chromosomes within chelonians. PMID- 26842822 TI - Comparing the Efficiency of Hospitals in Italy and Germany: Nonparametric Conditional Approach Based on Partial Frontier. AB - Traditional nonparametric frontier techniques to measure hospital efficiency have been criticized for their deterministic nature and the inability to incorporate external factors into the analysis. Moreover, efficiency estimates represent a relative measure meaning that the implications from a hospital efficiency analysis based on a single-country dataset are limited by the availability of suitable benchmarks. Our first objective is to demonstrate the application of advanced nonparametric methods that overcome the limitations of the traditional nonparametric frontier techniques. Our second objective is to provide guidance on how an international comparison of hospital efficiency can be conducted using the example of two countries: Italy and Germany. We rely on a partial frontier of order-m to obtain efficiency estimates robust to outliers and extreme values. We use the conditional approach to incorporate hospital and regional characteristics into the estimation of efficiency. The obtained conditional efficiency estimates may deviate from the traditional unconditional efficiency estimates, which do not account for the potential influence of operational environment on the production possibilities. We nonparametrically regress the ratios of conditional to unconditional efficiency estimates to examine the relation of hospital and regional characteristics with the efficiency performance. We show that the two countries can be compared against a common frontier when the challenges of international data compatibility are successfully overcome. The results indicate that there are significant differences in the production possibilities of Italian and German hospitals. Moreover, hospital characteristics, particularly bed-size category, ownership status, and specialization, are significantly related to differences in efficiency performance across the analyzed hospitals. PMID- 26842823 TI - Measuring health indicators and allocating health resources: a DEA-based approach. AB - This paper suggests new empirical DEA models for the measurement of health indicators and the allocation of health resources. The proposed models were developed by first suggesting a population-based health indicator. By introducing the suggested indicator into DEA models, a new approach that solves the problem of health resource allocation has been developed. The proposed models are applied to an empirical study of Taiwan's health system. Empirical findings show that the suggested indicator can successfully accommodate the differences in health resource demands between populations, providing more reliable performance information than traditional indicators such as physician density. Using our models and a commonly used allocation mechanism, capitation, to allocate medical expenditures, it is found that the proposed model always obtains higher performance than those derived from capitation, and the superiority increases as allocated expenditures rise. PMID- 26842824 TI - How well will you FIT? Use of a modified MMI to assess applicants' compatibility with an emergency medicine residency program. AB - PURPOSE: Emergency medicine residency programs have evaluated the use of Multiple Mini Interviews (MMIs) for applicants. The authors developed an MMI-style method called the Fast Interview Track (FIT) to predict an applicant's 'fit' within an individual residency program. METHODS: Applicants meet with up to five residents and are asked one question by each. Residents score the applicant using a Likert scale from 1 to 5 on two questions: 'How well does the applicant think on his/her feet?' and 'How well do you think the applicant will fit in here?'. To assess how well these questions predicted a resident's 'fit', current residents scored fellow residents on these same questions. These scores were compared with the residents' interview FIT scores. A postmatch survey of applicants who did not match at this program solicited applicants' attitudes toward the FIT sessions. RESULTS: Among the junior class, the correlation between interview and current scores was significant for question 1 (rho=0.5192 [p=0.03]) and question 2 (rho=0.5753 [p=0.01]). Among seniors, Spearman's rho was statistically significant for question 2, though not statistically significant for question 1. The chi-square measure of high scores (4-5) versus low scores (1-3) found a statistically significant association between interview and current scores for interns and juniors. Of the 29 responses to the postmatch survey, 16 (55%) felt FIT sessions provided a good sense of the program's personality and only 6 (21%) disagreed. Nine (31%) felt FIT sessions positively impacted our program's ranking and 11 (38%) were 'Neutral'. Only two (7%) reported that FIT sessions negatively impacted their ranking of our program. CONCLUSIONS: FIT provided program leadership with a sense of an applicant's 'fit' within this program. Interview day scores correlated with scores received during residency. Most applicants report a positive experience with FIT sessions. FIT provides a useful tool to recruit applicants who fit with the residency program. PMID- 26842825 TI - A teach approach: visual mapping of chromosome translocation. PMID- 26842826 TI - DEVELOPMENT AND IMPLEMENTATION OF TOOLS FOR SELF-MONITORING OF STAFF EXPOSED TO 131I IN NUCLEAR MEDICINE CENTRES OF CHILE. AB - Currently in Chile, there are about 42 nuclear medicine centres that mainly use 99mTc and 131I in diagnostic and therapeutic procedures. Therefore, staff performs various tasks that increase the risk of internal incorporation and the need to implement routine monitoring programmes. This article shows tools for self-monitoring of staff who exposed to 131I from measurements in thyroid and urine samples, using the gamma cameras of Nuclear Medicine Units. Then, the calibration factors of gamma cameras of participating units were determined, and a one-worker dose was calculated due to internal incorporation, using an Excel spreadsheet for self-monitoring. The worker who handles 131I in one of the studied units was monitored for 6 months. The goal of this study is to implement a routine self-monitoring programme for the estimation of committed effective dose of staff exposed to 131I using gamma cameras in Nuclear Medicine Units of clinical centres in Chile. PMID- 26842827 TI - VISIBILITY OF STRUCTURES OF RELEVANCE FOR PATIENTS WITH CYSTIC FIBROSIS IN CHEST TOMOSYNTHESIS: INFLUENCE OF ANATOMICAL LOCATION AND OBSERVER EXPERIENCE. AB - The aims of this study were to assess the visibility of pulmonary structures in patients with cystic fibrosis (CF) in digital tomosynthesis (DTS) using computed tomography (CT) as reference and to investigate the dependency on anatomical location and observer experience. Anatomical structures in predefined regions of CT images from 21 patients were identified. Three observers with different levels of experience rated the visibility of the structures in DTS by performing a head to-head comparison with visibility in CT. Visibility of the structures in DTS was reported as equal to CT in 34 %, inferior in 52 % and superior in 14 % of the ratings. Central and peripheral lateral structures received higher visibility ratings compared with peripheral structures anteriorly, posteriorly and surrounding the diaphragm (p <= 0.001). Reported visibility was significantly higher for the most experienced observer (p <= 0.01). The results indicate that minor pathology can be difficult to visualise with DTS depending on location and observer experience. Central and peripheral lateral structures are generally well depicted. PMID- 26842828 TI - Legislative smoking bans for reducing harms from secondhand smoke exposure, smoking prevalence and tobacco consumption. AB - BACKGROUND: Smoking bans have been implemented in a variety of settings, as well as being part of policy in many jurisdictions to protect the public and employees from the harmful effects of secondhand smoke (SHS). They also offer the potential to influence social norms and the smoking behaviour of those populations they affect. Since the first version of this review in 2010, more countries have introduced national smoking legislation banning indoor smoking. OBJECTIVES: To assess the effects of legislative smoking bans on (1) morbidity and mortality from exposure to secondhand smoke, and (2) smoking prevalence and tobacco consumption. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register, MEDLINE, EMBASE, PsycINFO, CINAHL and reference lists of included studies. We also checked websites of various organisations. Date of most recent search; February 2015. SELECTION CRITERIA: We considered studies that reported legislative smoking bans affecting populations. The minimum standard was having an indoor smoking ban explicitly in the study and a minimum of six months follow-up for measures of smoking behaviour. Our search included a broad range of research designs including: randomized controlled trials, quasi-experimental studies (i.e. non-randomized controlled studies), controlled before-and-after studies, interrupted time series as defined by the Cochrane Effective Practice and Organisation of Care Group, and uncontrolled pre- and post-ban data. DATA COLLECTION AND ANALYSIS: One author extracted characteristics and content of the interventions, participants, outcomes and methods of the included studies and a second author checked the details. We extracted health and smoking behaviour outcomes. We did not attempt a meta-analysis due to the heterogeneity in design and content of the studies included. We evaluated the studies using qualitative narrative synthesis. MAIN RESULTS: There are 77 studies included in this updated review. We retained 12 studies from the original review and identified 65 new studies. Evidence from 21 countries is provided in this update, an increase of eight countries from the original review. The nature of the intervention precludes randomized controlled trials. Thirty-six studies used an interrupted time series study design, 23 studies use a controlled before-and-after design and 18 studies are before-and-after studies with no control group; six of these studies use a cohort design. Seventy-two studies reported health outcomes, including cardiovascular (44), respiratory (21), and perinatal outcomes (7). Eleven studies reported national mortality rates for smoking-related diseases. A number of the studies report multiple health outcomes. There is consistent evidence of a positive impact of national smoking bans on improving cardiovascular health outcomes, and reducing mortality for associated smoking related illnesses. Effects on respiratory and perinatal health were less consistent. We found 24 studies evaluating the impact of national smoke-free legislation on smoking behaviour. Evidence of an impact of legislative bans on smoking prevalence and tobacco consumption is inconsistent, with some studies not detecting additional long-term change in existing trends in prevalence. AUTHORS' CONCLUSIONS: Since the first version of this review was published, the current evidence provides more robust support for the previous conclusions that the introduction of a legislative smoking ban does lead to improved health outcomes through reduction in SHS for countries and their populations. The clearest evidence is observed in reduced admissions for acute coronary syndrome. There is evidence of reduced mortality from smoking-related illnesses at a national level. There is inconsistent evidence of an impact on respiratory and perinatal health outcomes, and on smoking prevalence and tobacco consumption. PMID- 26842829 TI - Studies on the binding sites of IgG2 monoclonal antibodies recognized by terpyridine-based affinity ligands. AB - This investigation has examined the origin of the molecular recognition associated with the interaction of monoclonal IgG2's with terpyridine-based ligands immobilized onto agarose-derived chromatographic adsorbents. Isothermal titration calorimetric (ITC) methods have been employed to acquire thermodynamic data associated with the IgG2-ligand binding. These ITC investigations have documented that different enthalpic and entropic processes are involved depending on the nature of the chemical substituents in the core structure of the terpyridinyl moiety. In addition, molecular docking studies have been carried out with IgG2 structures with the objective to identify possible ligand binding sites and key interacting amino acid residues. These molecular docking experiments with the different terpyridine-based ligands have shown that all of the examined ligands can potentially undergo favorable interactions with a site located within the Fab region of the IgG2. However, another favorable binding site was also identified from the docking poses to exist within the Fc region of the IgG2 for some, but not all, of the ligands studied. These investigations have provided a basis to elucidate the unique binding properties and chromatographic behaviors shown by several substituted terpyridine ligands in their interaction with IgGs of different isotype. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26842830 TI - Performance analysis of multiple Indoor Positioning Systems in a healthcare environment. AB - BACKGROUND: The combination of an aging population and nursing staff shortages implies the need for more advanced systems in the healthcare industry. Many key enablers for the optimization of healthcare systems require provisioning of location awareness for patients (e.g. with dementia), nurses, doctors, assets, etc. Therefore, many Indoor Positioning Systems (IPSs) will be indispensable in healthcare systems. However, although many IPSs have been proposed in literature, most of these have been evaluated in non-representative environments such as office buildings rather than in a hospital. METHODS: To remedy this, the paper evaluates the performance of existing IPSs in an operational modern healthcare environment: the "Sint-Jozefs kliniek Izegem" hospital in Belgium. The evaluation (data-collecting and data-processing) is executed using a standardized methodology and evaluates the point accuracy, room accuracy and latency of multiple IPSs. To evaluate the solutions, the position of a stationary device was requested at 73 evaluation locations. By using the same evaluation locations for all IPSs the performance of all systems could objectively be compared. RESULTS: Several trends can be identified such as the fact that Wi-Fi based fingerprinting solutions have the best accuracy result (point accuracy of 1.21 m and room accuracy of 98%) however it requires calibration before use and needs 5.43 s to estimate the location. On the other hand, proximity based solutions (based on sensor nodes) are significantly cheaper to install, do not require calibration and still obtain acceptable room accuracy results. CONCLUSION: As a conclusion of this paper, Wi-Fi based solutions have the most potential for an indoor positioning service in case when accuracy is the most important metric. Applying the fingerprinting approach with an anchor installed in every two rooms is the preferred solution for a hospital environment. PMID- 26842831 TI - Is Emotional Lability Distinct From "Angry/Irritable Mood," "Negative Affect," or Other Subdimensions of Oppositional Defiant Disorder in Children With ADHD? AB - OBJECTIVE: Emotional lability (EL) and oppositional defiant disorder (ODD) frequently co-occur with ADHD. This study evaluates whether EL merely represents the negative "mood/affect" component of ODD or forms a distinct dimension. METHOD: EL and ODD data from 1,317 ADHD participants were analyzed using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) for binary data. RESULTS: Within ADHD, 39.4% children had ODD and 42.6% had EL. A sizable proportion expressed only either ODD or EL: 16.6% had ODD-only, 19.7% had EL-only, and 22.9% expressed both. In both EFA and CFA, EL forms a separate dimension from ODD items and the "mood/affect" subdimensions (whether classified by Diagnostic and Statistical Manual of Mental Disorders [5th ed.; DSM-5] or the Burke et al. models or the de novo ODD subdimensions derived from our data). This factorial structure remains invariant across gender. CONCLUSION: EL is distinct from ODD and its "mood/affect" subdimensions. In line with emerging evidence, our findings provide further evidence of factorial validity for EL as a separate construct from ODD. PMID- 26842833 TI - High production of CH4 and H2 by reducing PET waste water using a non-diaphragm based electrochemical method. AB - In recent years, the worldwide use of polyethylene terephthalate (PET) has increased exponentially. PET wastewater contains ethylene glycol (EG) and terephthalic acid (TPA). In this study, we present a unique method for producing combustible gases like CH4 and H2 from PET wastewater by electrochemical reaction of EG and TPA. The non-diaphragm-based electrochemical (NDE) method was used to treat PET wastewater. The electrochemical removal of EG and TPA from PET wastewater was examined and the optimal conditions for their reduction to CH4 and H2 were determined. Using the proposed system, 99.9% of the EG and TPA present in the PET wastewater samples were degraded to produce CH4 and H2, at applied voltages lower than 5 V. The highest Faradaic efficiency achieved for EG and TPA reduction was 62.2% (CH4, 25.6%; H2, 36.6%), at an applied voltage of 0.8 V. Remarkably, CH4 was produced from EG decomposition and H2 from TPA decomposition. To the best of our knowledge, this is the first reported instance of CH4 and H2 production from EG and TPA, respectively. The electrochemical reductive treatment will be an important discovery for reducing water contamination and replacing fossil fuels with respect to generating green energy. PMID- 26842832 TI - Incidental findings in emergency imaging: frequency, recommendations, and compliance with consensus guidelines. AB - The purpose of this study was to evaluate the frequency of incidental findings (IFs) in emergency department (ED) imaging reports and evaluate the adherence of imaging recommendations to consensus societal guidelines for IFs. A retrospective review of consecutive ED computed tomography (CT) and ultrasonography (US) reports from two university-affiliated EDs over a 2-month period was performed. Each imaging report was reviewed in its entirety, and incidental findings were documented along with recommendations for additional imaging. Imaging recommendations were compared to published societal guidelines from the American College of Radiology (ACR) and Fleischner Society. Three thousand one hundred thirty-one total cases consisting of 1967 CTs and 1164 US contained 514 incidental findings (16.4 %), with 329 CT IFs (64 %) and 185 US IFs (36 %). The ovary was the most common organ for an IF (n = 214, 42 %). Of all IFs, 347 (67.5 %) recommendations were concordant with societal guidelines and 167 (32.5 %) were discordant. 39.8 % of CT recommendations were discordant, while 19.5 % of US recommendations were discordant (p < 0.0001). Incidental findings are commonly encountered in the emergent setting. Variable adherence to societal guidelines is noted. Targeted radiologist education and technological solutions may decrease rates of discordance. PMID- 26842834 TI - Grabbing brain activity on the go. PMID- 26842835 TI - Exploring the chemistry and evolution of the isomerases. AB - Isomerization reactions are fundamental in biology, and isomers usually differ in their biological role and pharmacological effects. In this study, we have cataloged the isomerization reactions known to occur in biology using a combination of manual and computational approaches. This method provides a robust basis for comparison and clustering of the reactions into classes. Comparing our results with the Enzyme Commission (EC) classification, the standard approach to represent enzyme function on the basis of the overall chemistry of the catalyzed reaction, expands our understanding of the biochemistry of isomerization. The grouping of reactions involving stereoisomerism is straightforward with two distinct types (racemases/epimerases and cis-trans isomerases), but reactions entailing structural isomerism are diverse and challenging to classify using a hierarchical approach. This study provides an overview of which isomerases occur in nature, how we should describe and classify them, and their diversity. PMID- 26842836 TI - In vivo imaging reveals an essential role of vasoconstriction in rupture of the ovarian follicle at ovulation. AB - Rupture of the ovarian follicle releases the oocyte at ovulation, a timed event that is critical for fertilization. It is not understood how the protease activity required for rupture is directed with precise timing and localization to the outer surface, or apex, of the follicle. We hypothesized that vasoconstriction at the apex is essential for rupture. The diameter and blood flow of individual vessels and the thickness of the apical follicle wall were examined over time to expected ovulation using intravital multiphoton microscopy. Vasoconstriction of apical vessels occurred within hours preceding follicle rupture in wild-type mice, but vasoconstriction and rupture were absent in Amhr2(cre/+)SmoM2 mice in which follicle vessels lack the normal association with vascular smooth muscle. Vasoconstriction is not simply a response to reduced thickness of the follicle wall; vasoconstriction persisted in wild-type mice when thinning of the follicle wall was prevented by infusion of protease inhibitors into the ovarian bursa. Ovulation was inhibited by preventing the periovulatory rise in the expression of the vasoconstrictor endothelin 2 by follicle cells of wild-type mice. In these mice, infusion of vasoconstrictors (either endothelin 2 or angiotensin 2) into the bursa restored the vasoconstriction of apical vessels and ovulation. Additionally, infusion of endothelin receptor antagonists into the bursa of wild-type mice prevented vasoconstriction and follicle rupture. Processing tissue to allow imaging at increased depth through the follicle and transabdominal ultrasonography in vivo showed that decreased blood flow is restricted to the apex. These results demonstrate that vasoconstriction at the apex of the follicle is essential for ovulation. PMID- 26842838 TI - Systems vaccinology informs influenza vaccine immunogenicity. PMID- 26842839 TI - Breathing room for early animals. PMID- 26842837 TI - Identification of amino acid networks governing catalysis in the closed complex of class I terpene synthases. AB - Class I terpene synthases generate the structural core of bioactive terpenoids. Deciphering structure-function relationships in the reactive closed complex and targeted engineering is hampered by highly dynamic carbocation rearrangements during catalysis. Available crystal structures, however, represent the open, catalytically inactive form or harbor nonproductive substrate analogs. Here, we present a catalytically relevant, closed conformation of taxadiene synthase (TXS), the model class I terpene synthase, which simulates the initial catalytic time point. In silico modeling of subsequent catalytic steps allowed unprecedented insights into the dynamic reaction cascades and promiscuity mechanisms of class I terpene synthases. This generally applicable methodology enables the active-site localization of carbocations and demonstrates the presence of an active-site base motif and its dominating role during catalysis. It additionally allowed in silico-designed targeted protein engineering that unlocked the path to alternate monocyclic and bicyclic synthons representing the basis of a myriad of bioactive terpenoids. PMID- 26842841 TI - Ln3I5(S2N2)(S2)(THF)10 - a new type of molecular compounds. AB - Unprecedented complexes of the composition Ln3I5(S2N2)(S2)(THF)10 were obtained in the reactions of neodymium and dysprosium iodide-nitrides with sulfur. The inorganic core of the molecules contains the cyclic fragments Ln(MU-S2)Ln, LnSNSN and LnSN. Ten of the fourteen atoms of the core are coplanar, the remaining four S2 and I2 atoms lie in the other two orthogonal planes. The dysprosium complex upon excitation with UV light exhibits the metal-centered luminescence characteristic of the Dy(3+) ion. Geometric parameters of the molecules, computational data, electron spectroscopy and fluorescence suggest the existence of some conjugation in the mentioned heterocycles. PMID- 26842840 TI - Space: A Final Frontier for Vacuolar Pathogens. AB - There is a fundamental gap in our understanding of how a eukaryotic cell apportions the limited space within its cell membrane. Upon infection, a cell competes with intracellular pathogens for control of this same precious resource. The struggle between pathogen and host provides us with an opportunity to uncover the mechanisms regulating subcellular space by understanding how pathogens modulate vesicular traffic and membrane fusion events to create a specialized compartment for replication. By comparing several important intracellular pathogens, we review the molecular mechanisms and trafficking pathways that drive two space allocation strategies, the formation of tight and spacious pathogen containing vacuoles. Additionally, we discuss the potential advantages of each pathogenic lifestyle, the broader implications these lifestyles might have for cellular biology and outline exciting opportunities for future investigation. PMID- 26842842 TI - The Neural Basis of Postural Instability Gait Disorder Subtype of Parkinson's Disease: A PET and fMRI Study. AB - AIMS: The aim of this study is to further uncover the neural basis of postural instability gait disorder (PIGD) subtype of Parkinson's disease. METHODS: With F 18 fluorodeoxyglucose PET (FDG-PET), brain glucose metabolism of patients with PIGD (n = 15) was compared with healthy controls (n = 17) and tremor-dominant (TD) patients (n = 15), and the correlation between metabolism and PIGD symptoms was also assessed. Within PIGD symptom-correlated hypometabolic areas, the relationship of functional connectivity (FC) with motor and cognitive symptoms was examined by using functional MRI. RESULTS: Compared with controls, patients with PIGD displayed a distributed pattern of brain hypometabolism including striatal, frontal, and parietal areas. Relative to the pattern of TD patients, the pattern of patients with PIGD had additional metabolic decreases in caudate and inferior parietal lobule (IPL, Brodmann area [BA] 40). In PIGD group, the metabolic reductions in IPL (BA 40), middle frontal gyrus (MFG, BA 9) and fusiform gyrus (FG, BA 20) were associated with severe PIGD symptoms. Regions showing such correlation were chosen for further seed-based FC analysis. Decreased FC within the prefrontal-parietal network (between the MFG and IPL) was associated with severe PIGD symptoms. CONCLUSION: The involvement of the caudate, FG, and prefrontal-parietal network may be associated with the prominent gait impairments of PIGD subtype. Our findings expand the pathophysiological knowledge of PIGD subtype and provide valuable information for potential neuromodulation therapies alleviating gait disorders. PMID- 26842843 TI - Detemir is non-inferior to NPH insulin in women with pregestational type 2 diabetes and gestational diabetes mellitus. PMID- 26842844 TI - Differences in predictors of 5-year survival over a 10-year period in two cohorts of elderly nursing home residents in Sweden. AB - AIM: The aim was to compare 5-year survival in two included cohorts (from year 2000 and year 2007) of 249 nursing home residents (NHR) in this retrospective, comparative study. METHODS: The cohorts were compared regarding chronic diseases, medication, physical/cognitive/nutritional status, body mass index, body temperature and 5-year mortality. Factors correlated with 5-year survival were determined using Cox regression analysis. RESULTS: In average, cohort 2007 survived 31 +/- 16 months and cohort 2000, 38 +/- 13 months, p < 0.001. Dementia, ageing and circulatory failure were more common as cause of death 2007, while stroke, chronic obstructive pulmonary disease (COPD) and pneumonia were less common, compared with 2000. NHR belonging to cohort 2007 were significantly older when admitted to nursing homes (NH), more dependent in activities of daily living (ADL), had dementia, stroke, autoimmune disease and treatment with antidepressants, while malnutrition and treatment with paracetamol were more common 2000. In 2000, medication with antidepressants, the presence of stroke and diabetes, irrespective of gender, and in women cardiovascular disease, two to threefold significantly increased survival, while autoimmune disease, influenza vaccination and dependency in ADL decreased survival. In 2007, maintaining BMI, irrespective of gender, and autoimmune disease and COPD in women significantly increased survival, while malnutrition, influenza vaccination, dependency in ADL and medication with sedatives/tranquillisers or paracetamol severely reduced survival. CONCLUSIONS: The present results indicate a trend that individuals are older and frailer when admitted to NH and that survival time after admission has been shortened. Hence, the need of daily support and care has increased, irrespective of housing. Also, predictors of survival, possible to influence, have changed. PMID- 26842845 TI - Profilin potentiates chemotherapeutic agents mediated cell death via suppression of NF-kappaB and upregulation of p53. AB - The molecular mechanism by which Profilin acts as a tumor suppressor is still unclear. Several chemotherapeutic agents, used till date either have unfavorable side effects or acquired resistance in tumor cells. Our findings show that Profilin enhances cell death mediated by several chemotherapeutic-agents. The activation of NF-kappaB and its dependent genes, mediated by paclitaxel and vinblastine, was completely inhibited in Profilin overexpressing cells. This inhibition was due to the Profilin mediated attenuation of IkappaBalpha degradation, thereby preventing p65 nuclear translocation and low NF-kappaB DNA binding activity.Moreover, Profilin increases level of p53 in the presence of known inducers, such as doxorubicin, vinblastine, and benzofuran. This increased p53 level leads to enhanced cell death as indicated by activation of caspases 3, 8, 9, which results in cleavage of PARP.Furthermore, knocking down of p53 in Profilin overexpressing cells leads to decreased cell death. Ectopic expression of Profilin in HCT116 p53 knock out cells showed lesser cell death as compared to the HCT116 p53 wild type cells. For the first time, we provide evidences, which suggest that Profilin synergizes with chemotherapeutic drugs to induce tumor cell death by regulating NF-kappaB and p53. Thus, modulation of Profilin may be a useful strategy for effective combination therapy. PMID- 26842846 TI - Mycobacterium avium MAV2052 protein induces apoptosis in murine macrophage cells through Toll-like receptor 4. AB - Mycobacterium avium and its sonic extracts induce apoptosis in macrophages. However, little is known about the M. avium components regulating macrophage apoptosis. In this study, using multidimensional fractionation, we identified MAV2052 protein, which induced macrophage apoptosis in M. avium culture filtrates. The recombinant MAV2052 induced macrophage apoptosis in a caspase dependent manner. The loss of mitochondrial transmembrane potential (DeltaPsim), mitochondrial translocation of Bax, and release of cytochrome c from mitochondria were observed in macrophages treated with MAV2052. Further, reactive oxygen species (ROS) production was required for the apoptosis induced by MAV2052. In addition, ROS and mitogen-activated protein kinases were involved in MAV2052 mediated TNF-alpha and IL-6 production. ROS-mediated activation of apoptosis signal-regulating kinase 1 (ASK1)-JNK pathway was a major signaling pathway for MAV2052-induced apoptosis. Moreover, MAV2052 bound to Toll-like receptor (TLR) 4 molecule and MAV2052-induced ROS production, DeltaPsim loss, and apoptosis were all significantly reduced in TLR4(-/-) macrophages. Altogether, our results suggest that MAV2052 induces apoptotic cell death through TLR4 dependent ROS production and JNK pathway in murine macrophages. PMID- 26842847 TI - The roles of juvenile hormone, insulin/target of rapamycin, and ecydsone signaling in regulating body size in Drosophila. AB - Understanding how organisms regulate their body size has interested biologists for decades. Recent work has shown that both insulin/target of rapamycin (TOR) signaling and the steroid hormone ecdysone act to regulate rates of growth and the duration of the growth period in the fruit fly, Drosophila melanogaster. Our recent work has uncovered a third level of interaction, whereby juvenile hormone (JH) regulates levels of both ecdysone and insulin/TOR signaling to control growth rates. These studies highlight a complex network of interactions involved in regulating body and organ size. PMID- 26842848 TI - Measure transcript integrity using RNA-seq data. AB - BACKGROUND: Stored biological samples with pathology information and medical records are invaluable resources for translational medical research. However, RNAs extracted from the archived clinical tissues are often substantially degraded. RNA degradation distorts the RNA-seq read coverage in a gene-specific manner, and has profound influences on whole-genome gene expression profiling. RESULT: We developed the transcript integrity number (TIN) to measure RNA degradation. When applied to 3 independent RNA-seq datasets, we demonstrated TIN is a reliable and sensitive measure of the RNA degradation at both transcript and sample level. Through comparing 10 prostate cancer clinical samples with lower RNA integrity to 10 samples with higher RNA quality, we demonstrated that calibrating gene expression counts with TIN scores could effectively neutralize RNA degradation effects by reducing false positives and recovering biologically meaningful pathways. When further evaluating the performance of TIN correction using spike-in transcripts in RNA-seq data generated from the Sequencing Quality Control consortium, we found TIN adjustment had better control of false positives and false negatives (sensitivity = 0.89, specificity = 0.91, accuracy = 0.90), as compared to gene expression analysis results without TIN correction (sensitivity = 0.98, specificity = 0.50, accuracy = 0.86). CONCLUSION: TIN is a reliable measurement of RNA integrity and a valuable approach used to neutralize in vitro RNA degradation effect and improve differential gene expression analysis. PMID- 26842849 TI - A Common Variant in CLDN14 is Associated with Primary Biliary Cirrhosis and Bone Mineral Density. AB - Primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, has been associated with increased incidence of osteoporosis. Intriguingly, two PBC susceptibility loci identified through genome-wide association studies are also involved in bone mineral density (BMD). These observations led us to investigate the genetic variants shared between PBC and BMD. We evaluated 72 genome-wide significant BMD SNPs for association with PBC using two European GWAS data sets (n = 8392), with replication of significant findings in a Chinese cohort (685 cases, 1152 controls). Our analysis identified a novel variant in the intron of the CLDN14 gene (rs170183, Pfdr = 0.015) after multiple testing correction. The three associated variants were followed-up in the Chinese cohort; one SNP rs170183 demonstrated consistent evidence of association in diverse ethnic populations (Pcombined = 2.43 * 10(-5)). Notably, expression quantitative trait loci (eQTL) data revealed that rs170183 was correlated with a decline in CLDN14 expression in both lymphoblastoid cell lines and T cells (Padj = 0.003 and 0.016, respectively). In conclusion, our study identified a novel PBC susceptibility variant that has been shown to be strongly associated with BMD, highlighting the potential of pleiotropy to improve gene discovery. PMID- 26842852 TI - The future of recycling in the United States. PMID- 26842850 TI - Community paramedicine model of care: an observational, ethnographic case study. AB - BACKGROUND: Community paramedicine programs have emerged throughout North America and beyond in response to demographic changes and health system reform. Our aim was to identify and analyse how community paramedics create and maintain new role boundaries and identities in terms of flexibility and permeability and through this develop and frame a coherent community paramedicine model of care that distinguish the model from other innovations in paramedic service delivery. METHODS: Using an observational ethnographic case study approach, we collected data through interviews, focus groups and field observations. We then applied a combination of thematic analysis techniques and boundary theory to develop a community paramedicine model of care. RESULTS: A model of care that distinguishes community paramedicine from other paramedic service innovations emerged that follows the mnemonic RESPIGHT: Response to emergencies; Engaging with communities; Situated practice; Primary health care; Integration with health, aged care and social services; Governance and leadership; Higher education; Treatment and transport options. CONCLUSIONS: Community engagement and situated practice distinguish community paramedicine models of care from other paramedicine and out-of-hospital health care models. Successful community paramedicine programs are integrated with health, aged care and social services and benefit from strong governance and paramedic leadership. PMID- 26842851 TI - Utility of FDG-PET/CT in the diagnosis of IgG4-related diseases. AB - OBJECTIVES: The purpose of this work is to evaluate the usefulness of 18F fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging in management of IgG4-related disease (IgG4-RD) by retrospective analysis of PET/CT results in IgG4-RD patients. METHODS: Twenty-six patients diagnosed with IgG4-RD according to Japanese diagnostic criteria who underwent 18F-FDG-PET/CT scans in the PLA General Hospital from January 2010 to May 2015 were enrolled in the study. Their clinical presentations and 18F-FDG-PET/CT findings were analysed. RESULTS: A total of 26 patients (20 men; 6 women) with a mean age of 53.8 years (range 35-71 years) and mean treatment course of 7.1 months (range 0.33-72 months) who underwent 18F-FDG-PET/CT scans were analysed. CRP was relatively low in all patients (mean 0.79 mg/dl). 18F-FDG-PET/CT images confirmed that two or more organs were involved in all patients, and average SUV values for involved organs was 4.14 (range 0.30-8.78). Eleven patients were misdiagnosed with submandibular tumours, pancreatic cancer, pancreatitis, pulmonary interstitial fibrosis, retroperitoneal fibrosis or systemic vasculitis prior to 18F-FDG-PET/CT imaging. CONCLUSIONS: 18F-FDG-PET/CT imaging is a useful tool for the differential diagnosis of IgG4-RD, and for mapping involved organs, guiding biopsy, and monitoring treatment response. PMID- 26842853 TI - 5-Lipoxygenase-activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation. AB - Leukotrienes (LTs) are proinflammatory lipid mediators formed from arachidonic acid in a 2-step reaction catalyzed by 5-lipoxygenase (5-LOX) requiring the formation of 5-HPETE [5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid] and its subsequent transformation to LTA4 5-LOX is thought to receive arachidonic acid from the nuclear membrane-embedded 5-LOX-activating protein (FLAP). The crystal structure of 5-LOX revealed an active site concealed by F177 and Y181 (FY cork). We examined the influence of the FY cork on 5-LOX activity and membrane binding in HEK293 cells in the absence and presence of FLAP. Uncapping the 5-LOX active site by mutation of F177 and/or Y181 to alanine (5-LOX-F177A, 5-LOX-Y181A, 5-LOX-F177/Y181A) resulted in delayed and diminished 5-LOX membrane association in A23187-stimulated cells. For 5-LOX-F177A and 5-LOX-F177/Y181A, formation of 5 LOX products was dramatically reduced relative to 5-LOX-wild type (wt). Strikingly, coexpression of FLAP in A23187-activated HEK293 cells effectively restored formation of 5-H(p)ETE (5-hydroxy- and 5-peroxy-6-trans-8,11,14-cis eicosatetraenoic acid) by these same 5-LOX mutants (~60-70% 5-LOX-wt levels) but not of LTA4 hydrolysis products. Yet 5-LOX-Y181A generated 5-H(p)ETE at levels comparable to 5-LOX-wt but reduced LTA4 hydrolysis products. Coexpression of FLAP partially restored LTA4 hydrolysis product formation by 5-LOX-Y181A. Together, the data suggest that the concealed FY cork impacts membrane association and that FLAP may help shield an uncapped active site.-Gerstmeier, J., Newcomer, M. E., Dennhardt, S., Romp, E., Fischer, J., Werz, O., Garscha, U. 5-Lipoxygenase activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation. PMID- 26842854 TI - Small-molecule CFTR activators increase tear secretion and prevent experimental dry eye disease. AB - Dry eye disorders, including Sjogren's syndrome, constitute a common problem in the aging population, with limited effective therapeutic options available. The cAMP-activated Cl(-) channel cystic fibrosis transmembrane conductance regulator (CFTR) is a major prosecretory channel at the ocular surface. We investigated whether compounds that target CFTR can correct the abnormal tear film in dry eye. Small-molecule activators of human wild-type CFTR identified by high-throughput screening were evaluated in cell culture and in vivo assays, to select compounds that stimulate Cl(-)-driven fluid secretion across the ocular surface in mice. An aminophenyl-1,3,5-triazine, CFTRact-K089, fully activated CFTR in cell cultures with EC50 ~250 nM and produced an ~8.5 mV hyperpolarization in ocular surface potential difference. When delivered topically, CFTRact-K089 doubled basal tear volume for 4 h and had no effect in CF mice. CFTRact-K089 showed sustained tear film bioavailability without detectable systemic absorption. In a mouse model of aqueous-deficient dry eye produced by lacrimal ablation, topical administration of 0.1 nmol CFTRact-K089 3 times daily restored tear volume to basal levels, preventing corneal epithelial disruption when initiated at the time of surgery and reversing it when started after development of dry eye. Our results support the potential utility of CFTR-targeted activators as a novel prosecretory treatment for dry eye.-Flores, A. M., Casey, S. D., Felix, C. M., Phuan, P. W., Verkman, A. S., Levin, M. H. Small-molecule CFTR activators increase tear secretion and prevent experimental dry eye disease. PMID- 26842855 TI - The arousing power of everyday materials: an analysis of the physiological and behavioral responses to visually and tactually presented textures. AB - Previous research has shown that during multisensory perception, vision frequently dominates over the other sensory modalities. However, it is still unclear whether sensory dominance also implies the generation of a greater state of arousal. Here, we assess the psycho-physiological reactions to different materials when presented tactually (Group 1) or visually (Group 2). In Group 1, the participants' forearm was stroked with different textures (satin, tinfoil, leather, sandpaper and abrasive sponge), by either a male or a female experimenter. The speed of stimulation was set to elicit a vigorous response of C tactile afferents, involved in the perception of the more pleasant aspects of touch. The participants were asked to rate the pleasantness of the stimulation. In Group 2, the same textures were presented only visually, and the participants were asked to rate the imagined pleasantness of being touched by those stimuli. Skin conductance responses were recorded in both groups. The results revealed that the tactile presentation of the stimuli led to higher skin conductance responses than the visual presentation; this difference was higher for women than for men. Smooth materials were perceived as more pleasant than rough materials, but no differences in terms of skin conductance responses were found among them. Moreover, the textures were rated as less pleasant when presented visually than when presented tactually. These findings are relevant to understand how physiological arousal is modulated by different senses and to elucidate the mechanisms involved in hedonic tactile perception. PMID- 26842857 TI - Wollaston's effect in infants: Do infants integrate eye and head information in gaze perception? AB - The current study examined infants' sensitivity to Wollaston's effect: When identical eyes are placed in differently angled faces, the perceived gaze direction shifts toward the orientation of the face such that physically, the direct gaze is perceived as averted toward the orientation of the face. Consistent with Wollaston's effect, we found that looking toward direct and averted gaze by 4- to 5- and 7- to 8-month-olds (n = 40) was affected by the head orientation context. These results demonstrate that infants aged 4 to 5 and 7 to 8 months integrate eye and head information to perceive another's gaze direction. In light of recent psychophysical findings, the current results suggest that the visual function supporting constant gaze perception across head rotation is already at work by 4 to 5 months of age. PMID- 26842858 TI - Who are you expecting? Biases in face perception reveal prior expectations for sex and age. AB - A person's appearance contains a wealth of information, including indicators of their sex and age. Because first impressions can set the tone of subsequent relationships, it is crucial we form an accurate initial impression. Yet prior expectation can bias our decisions: Studies have reported biases to respond "male" when asked to report a person's sex from an image of their face and to place their age closer to their own. Perceptual expectation effects and cognitive response biases may both contribute to these inaccuracies. The current research used a Bayesian modeling approach to establish the perceptual biases involved when estimating the sex and age of an individual from their face. We demonstrate a perceptual bias for male and older faces evident under conditions of uncertainty. This suggests the well-established male bias is perceptual in origin and may be impervious to cognitive control. In comparison, the own age anchor effect is not operationalized at the perceptual level: The perceptual expectation is for a face of advanced age. Thus, distinct biases in the estimation of age operate at the perceptual and cognitive levels. PMID- 26842859 TI - Uniformity of accommodation across the visual field. AB - We asked the question: Does accommodation change the eye's focusing power equally over the central visual field in emmetropic and myopic adult eyes? To answer this question we modified our laboratory scanning wavefront aberrometer to rapidly measure ocular refractive state over the central 30 degrees diameter of visual field as a function of foveal accommodative demand. On average, ocular refractive state changed uniformly over the central visual field as the eye accommodated up to 6 D. Visual field maps of accommodative error (relative to a spherical target surface of constant vergence) reveal subtle patterns of deviation on the order of +/- 0.5 D that are unique to the individual and relatively invariant to changes in accommodative state. Population mean maps for accommodative error are remarkably uniform across the central visual field, indicating the retina of the hypothetical "average eye" is conjugate to a sphere of constant target vergence for all states of accommodation, even though individual eyes might deviate from the mean due to random variations. No systematic difference between emmetropic and myopic eyes was evident. Since accuracy of accommodation across the central visual field is similar to that measured in the fovea, loss of image quality due to accommodative errors, which potentially drives myopia and may affect many aspects of visual function, will be similar across the central retina. PMID- 26842856 TI - Interference between oculomotor and postural tasks in 7-8-year-old children and adults. AB - Several studies in adults having observed the effect of eye movements on postural control provided contradictory results. In the present study, we explored the effect of various oculomotor tasks on postural control and the effect of different postural tasks on eye movements in eleven children (7.8 +/- 0.5 years) and nine adults (30.4 +/- 6.3 years). To vary the difficulty of the oculomotor task, three conditions were tested: fixation, prosaccades (reactive saccades made toward the target) and antisaccades (voluntary saccades made in the direction opposite to the visual target). To vary the difficulty of postural control, two postural tasks were tested: Standard Romberg (SR) and Tandem Romberg (TR). Postural difficulty did not affect oculomotor behavior, except by lengthening adults' latencies in the prosaccade task. For both groups, postural control was altered in the antisaccade task as compared to fixation and prosaccade tasks. Moreover, a ceiling effect was found in the more complex postural task. This study highlighted a cortical interference between oculomotor and postural control systems. PMID- 26842860 TI - Elastic spheres can walk on water. AB - Incited by public fascination and engineering application, water-skipping of rigid stones and spheres has received considerable study. While these objects can be coaxed to ricochet, elastic spheres demonstrate superior water-skipping ability, but little is known about the effect of large material compliance on water impact physics. Here we show that upon water impact, very compliant spheres naturally assume a disk-like geometry and dynamic orientation that are favourable for water-skipping. Experiments and numerical modelling reveal that the initial spherical shape evolves as elastic waves propagate through the material. We find that the skipping dynamics are governed by the wave propagation speed and by the ratio of material shear modulus to hydrodynamic pressure. With these insights, we explain why softer spheres skip more easily than stiffer ones. Our results advance understanding of fluid-elastic body interaction during water impact, which could benefit inflatable craft modelling and, more playfully, design of elastic aquatic toys. PMID- 26842861 TI - Power Outage-Inadequate Surgeon Performance Measures Leave Patients in the Dark. PMID- 26842863 TI - Fish oil for OA? Don't give up yet. PMID- 26842862 TI - Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection. AB - BACKGROUND: Trachoma, a preventable blinding eye disease, is initiated by ocular infection with Chlamydia trachomatis (Ct). We previously showed that microRNAs (miR) -147b and miR-1285 were up-regulated in inflammatory trachomatous scarring. During the initial stage of disease, follicular trachoma with current Ct infection, the differential expression of miR has not yet been investigated. METHODS: Conjunctival samples were collected from 163 children aged 1-9 years old living in a trachoma-endemic region of Guinea Bissau, West Africa. Small RNA sequencing (RNAseq) was carried out on samples from five children with follicular trachoma and current Ct infection and five children with healthy conjunctivae and no Ct infection. Small RNAseq was also carried out on human epithelial cell lines infected with ocular Ct strains A2497 and isogenic plasmid-free A2497 in vitro. Results were validated by quantitative PCR (qPCR) in 163 clinical samples. RESULTS: Differential expression of RNAseq data identified 12 miR with changes in relative expression during follicular trachoma, of which 9 were confirmed as differentially expressed by qPCR (miR-155, miR-150, miR-142, miR-181b, miR-181a, miR-342, miR-132, miR-4728 and miR-184). MiR-155 and miR-184 expression had a direct relationship with the degree of clinical inflammation. MiR-155 was up regulated (OR = 2.533 ((95 % CI = 1.291-4.971); P = 0.0069) and miR-184 was down regulated (OR = 0.416 ((95 % CI = 0.300-0.578); P = 1.61*10(-7)) as the severity of clinical inflammation increased. Differential miR expression was not detected in HEp-2 or HCjE epithelial cells 48 h post infection with Ct in vitro. HCjE cells, a conjunctival epithelial cell line, had a markedly different miR background expression compared to HEp-2 cells. CONCLUSIONS: In follicular trachoma, expression of miR-155 and miR-184 is correlated with the severity of inflammation. This likely reflects host regulation of the immune response and a prolonged period of wound healing following the clearance of Ct. Prolonged healing may be associated with subsequent development of scarring trachoma. PMID- 26842864 TI - Zebrafish as a Model to Investigate Dynamin 2-Related Diseases. AB - Mutations in the dynamin-2 gene (DNM2) cause autosomal dominant centronuclear myopathy (CNM) and dominant intermediate Charcot-Marie-Tooth (CMT) neuropathy type B (CMTDIB). As the relation between these DNM2-related diseases is poorly understood, we used zebrafish to investigate the effects of two different DNM2 mutations. First we identified a new alternatively spliced zebrafish dynamin-2a mRNA (dnm2a-v2) with greater similarity to human DNM2 than the deposited sequence. Then we knocked-down the zebrafish dnm2a, producing defects in muscle morphology. Finally, we expressed two mutated DNM2 mRNA by injecting zebrafish embryos with human mRNAs carrying the R522H mutation, causing CNM, or the G537C mutation, causing CMT. Defects arose especially in secondary motor neuron formation, with incorrect branching in embryos injected with CNM-mutated mRNA, and total absence of branching in those injected with CMT-mutated mRNA. Muscle morphology in embryos injected with CMT-mutated mRNA appeared less regularly organized than in those injected with CNM-mutated mRNA. Our results showing, a continuum between CNM and CMTDIB phenotypes in zebrafish, similarly to the human conditions, confirm this animal model to be a powerful tool to investigate mutations of DNM2 in vivo. PMID- 26842865 TI - Nerve conduction studies in lower limb of elite Nepalese football players: an insight into neural adaptations. AB - BACKGROUND: The study was aimed to assess somatic neural alterations in lower limbs of elite Nepalese football players by comparing their nerve conduction parameters with non-athletic controls. METHODS: Players (N.=27, age 22.74+/-2.52 yrs.) with excellent cardio-respiratory fitness and presenting no signs of injuries, and sedentary controls (N.=29, age 23.41+/-2.95 yrs.) were recruited for the study. Standard nerve conduction techniques were applied to evaluate posterior tibial and sural nerves in the dominant and non-dominant limbs of each individual. Conduction velocity, onset latency, amplitude and duration of the motor and sensory evoked responses were recorded. RESULTS: The players had significantly lower resting mean heart rate, systolic and diastolic blood pressure than controls. Tibial compound muscle action potential (CMAP) showed higher amplitude as compared to controls; tibial proximal CMAP amplitude [(13.624+/-4.57) vs. (10.810+/-4.62) mV, P=0.035] of dominant leg, tibial proximal [(13.893+/-4.60) vs. (11.083+/-4.51) mV, P=0.045] and distal [(16.388+/ 3.62) vs. (13.958+/-4.65) mV, P=0.049] amplitude of non-dominant leg. Likewise, players had significantly shorter tibial CMAPs duration of each lower limb compared with corresponding limb of controls. Sural nerve of non-dominant leg revealed shortened sensory nerve action potential duration [(1.729+/-0.25) vs. (1.904+/-0.289) ms, P=0.018]. CONCLUSIONS: Increased tibial CMAP amplitude and decreased CMAP duration in players suggest excitation of more number of motor units and higher synchronicity of muscle fibers' discharge than in controls respectively. Higher amplitude can also be attributed to increase in muscle fiber size and/or efficiency of neuromuscular transmission. Increased synchronicity indirectly reflects narrow range of conduction velocity among tibial neurons. The adaptive changes in somatic nerves need more crucial research for exact identification of sites and the structures responsible. PMID- 26842866 TI - Sickle cell trait: what are the costs and benefits of screening? AB - INTRODUCTION: Eight percent of African Americans are carriers of the sickle cell trait. Some regard this as a benign anomaly, but others point to incidents of sudden exercise-related death, calling for a preliminary screening of either all athletes or those of African-American ancestry. This brief review considers the costs and benefits of such screening. EVIDENCE ACQUISITION: The Ovid/Health Star data-base was searched from 1996 to June 2015. 2014. The terms "exercise", "exercise therapy", "sports", "athletes", "physical activity/motor activity" and "physical fitness" were combined to yield 227,120 citations. Likewise, the terms "sickle cell trait", "sickle cell disease", "splenic infarction", "hemoglobin S" and "rhabdomyolysis" identified 12,325 citations. A combination of the 2 searches yielded 416 abstracts. EVIDENCE SYNTHESIS: Excluding items relating to animal research or forms of rhabdomyolysis other than sickling left 375 abstracts; 115 papers merited full examination. This material covered the risks of sickle cell trait and of screening (55 items), effects upon physical performance (31 items), cellular mechanisms (23 items), nutrition (4 items), and other topics (2 items). Supplemented material was drawn from reference lists and personal files. The tendency to sickling was provoked by excessive exercise relative to physical condition in hot or hypoxic conditions, and by local tissue acidosis, conditions that were best avoided by all athletes. The condition had little impact upon physical performance, but the relative risks of heat illness, exertional rhabdomyolysis, splenic infarction and sudden death were all increased by the sickle cell trait. The absolute number of critical incidents was nevertheless small, calling for close assessment of the costs and putative benefits of widespread screening. CONCLUSIONS: Sports physicians should be aware of the clinical picture of sickling and be prepared to treat it. Screening may be cost effective if targeted to black athletes involved in certain sports, although it has yet to be demonstrated how far the diagnosis of sickle cell trait reduces the risk of death when exercising in an adverse environment. A better tactic may be to reduce risks for all competitors by educating athletes and their coaches to adopt an intensity of training appropriate to the individual's physical condition, to maintain full hydration, and to avoid exposure to excessive heat and hypoxia. PMID- 26842868 TI - Physical and physiological demands in women pole dance: a single case study. AB - AIM: to investigate the physical and physiological demands of a pole dancer's performance studied during a simulated competition, lasting 3 min 30 sec. METHODS: one single woman pole dancer, (age: 22 years; height: 1.56m; body weight: 52kg; BMI: 21.4kg.m-2; estimated HRmax:192.6 bpm) participated in the study. Physical data pertaining to accelerations and rotational values were collected by the means of a tri-axial accelerometer device integrating three gyroscopes. A complete video footage was recorded using four video cameras, using different sampling rates. Blood Pressure, Heart Rates, Breathing Rates, Blood Lactate concentrations were recorded during the performance. RESULTS: Accelerations (positive and negative), along the vertical axis reached 2G and rotational movements around the pole, reached 400 degrees /s. Blood Pressure values ranged from 120/75 before and to 145/58 mmHg at the end of performance, respectively. Heart Rates reached a peak value of 96% of the Maximal Estimated Heart Rate (HRmax) and a mean %HRmax of 92.85 +/- 3.15% during the simulated competition. Breathing Rate reached a peak value of 37 bpm and a mean value during competition of 31.87+/-3.42 bpm. Blood Lactate concentration ranged from 10.2 to 10.7 mmol/L measured at 1 min and 5 min after the completion of the competition, respectively. CONCLUSIONS: The results of this case study confirm that the Pole Dance is a performing art requiring heavy physiological and physical demands on the performers. Specific training routines should be designed in order to cope efficiently with this physical activity, taking into account the performance model we provided with this study. PMID- 26842867 TI - Ten weeks of capoeira progressive training improved cardiovascular parameters in male practitioners. AB - BACKGROUND: The present study analyzed the effects of ten weeks of Capoeira progressive training program on the cardiovascular parameters of male practitioners. METHODS: Participants were assigned into two groups (capoeira, N.=10; 25.4+/-3.3 years; 24.2+/-2.2 kg.m2(-1) and Control, N.=08; 29.6+/-6.3 years; 26.4+/-4.4 kg.m2(-1)). The Capoeira group performed ten weeks of Capoeira progressive training program, being one session per week lasting 90 minutes each. The control group was instructed to avoid any exercise training program or intense physical activities during the experimental period. The blood pressure (BP), heart rate (HR), and rate pressure product (RPP), as well as HR variability (HRV) indicators were evaluated on resting, before and after intervention. RESULTS: A two-way ANOVA revealed a main effect of group by time interaction to HR (F=6.649, eta2=0.379; P=0.02), and HRV indicators (RRi: F=5.752, eta2=0.313; rMSSD: F=4.652, eta2=0.283; SD1: F=4.694, eta2=0.409, and pNN50: F=5.561, eta2=0.360; P<0.05). A main effect of time condition was verified for capoeira group (P<0.05) on HR (?=-6.6+/-6.0 bpm), RRi (?=80.1+/-65.4 ms), rMSSD (?=14.1+/ 11.6 ms), SD1 (?=10.0+/-8.2 ms), and pNN50 (?=11.3+/-9.7%). The between groups analysis identified significant differences (P<0.05) for the HR after intervention (capoeira: -8.6+/-6.9% vs. CONTROL: -0.7+/-3.9%). The comparison between capoeira vs. control for HRV indicators (RRi: ?=10.1+/-8.5% vs. 0.9+/ 7.6%; rMSSD: ?=37.8+/-32.9% vs. 2.9+/-31.3%; pNN50: ?=96.2+/-78.7% vs. 0.3+/ 54.1%; and SD1: ?=37.7+/-32.9% vs. 6.5+/-24.4%; respectively) differed to each other (P<0.05). CONCLUSIONS: Our findings showed that ten weeks of capoeira progressive training program improves both autonomic and cardiovascular parameters in male practitioners. PMID- 26842869 TI - The kinematics of table tennis racquet: differences between topspin strokes. AB - BACKGROUND: Studies of shot kinematics in table tennis have not been sufficiently described in the literature. The assessment of the racquet trajectory, its speed and time characteristics makes it possible to emphasize on certain technical elements in the training process in order, for example, to increase strength, speed of rotation or speed of the shot while maintaining its accuracy. The aim of this work was to measure selected kinematic parameters of table tennis racquet during forehand and backhand topspin shots, while considering the differences between these strokes in table tennis. METHODS: The measurements took place in a certified biomechanical laboratory using a motion analysis system. The study involved 12 female table tennis players in high-level sports training and performance. Each subject had to complete series of six tasks, presenting different varieties of topspin shots. RESULTS: The longest racquet trajectory was related to forehand shots, shots played against a ball with backspin and winner shots. The maximum racquet velocity was precisely in the moment of impact with the ball. The individual of velocity and distance were larger in the direction of the acting force, depending on the individual shot. CONCLUSIONS: Changing the type of topspin shot requires changes of time, velocity and primarily distance parameters as well as the direction of the playing racquet. The maximum speed of the racquet occurring at the moment of the impact is probably the most important principle in playing technique. The results can be directly used in improving training of table tennis techniques, especially in the application and use of topspin shots. PMID- 26842870 TI - The effect of levosulpiride on in vitro motor patterns in the human gastric fundus, antrum, and jejunum. AB - BACKGROUND: Levosulpiride is a 5HT4 agonist/D2 antagonist prokinetic agent used to improve gastric emptying in patients with functional dyspepsia or gastroparesis. The aim of this study was to characterize its effect on the main in vitro motility patterns in the human fundus, antrum, and jejunum. METHODS: Circular muscle strips from human stomach (antrum and fundus) and jejunum, obtained from 46 patients undergoing bariatric surgery, were studied using organ baths. Enteric motor neurons (EMNs) were stimulated by electrical field stimulation (EFS). KEY RESULTS: Levosulpiride, caused an increase in the EFS induced cholinergic contractions in the gastric antrum (+37 +/- 15.18% at 100 MUM, pEC50 = 4.46 +/- 0.14; p < 0.05, n = 8) and jejunum (+45.4 +/- 22.03% at 100 MUM, pEC50 = 3.78 +/- 6.81; p < 0.05, n = 5), but not in the gastric fundus. It also caused a slight decrease in tone and frequency of spontaneous contractions in the jejunum, but did not have any major effect on tone or spontaneous contractions in the stomach. It did not have any effect on EFS-induced relaxations mediated by nitric oxide (NO) in the stomach (antrum and fundus) and by NO and ATP in the jejunum. CONCLUSIONS & INFERENCES: Our results suggest that the prokinetic effects of levosulpiride in humans are mainly due to the facilitation of the release of acetylcholine by enteric motor neurons in the gastric antrum and the jejunum. PMID- 26842872 TI - Enhancing genomic laboratory reports: A qualitative analysis of provider review. AB - This study reports on the responses of physicians who reviewed provider and patient versions of a genomic laboratory report designed to communicate results of whole genome sequencing. Semi-structured interviews addressed concept communication, elements, and format of example genome reports. Analysis of the coded transcripts resulted in recognition of three constructs around communication of genome sequencing results: (1) Providers agreed that whole genomic sequencing results are complex and they welcomed a report that provided supportive interpretation information to accompany sequencing results; (2) Providers strongly endorsed a report that included active clinical guidance, such as reference to practice guidelines, if available; and (3) Providers valued the genomic report as a resource that would serve as the basis to facilitate communication of genome sequencing results with their patients and families. Providers valued both versions of the report, though they affirmed the need for a provider-oriented report. Critical elements of the report included clear language to explain the result, as well as consolidated yet comprehensive prognostic information with clear guidance over time for the clinical care of the patient. Most importantly, it appears a report with this design has the potential not only to return results but also serves as a communication tool to help providers and patients discuss and coordinate care over time. PMID- 26842871 TI - Evaluation of a self-management patient education program for patients with fibromyalgia syndrome: study protocol of a cluster randomized controlled trial. AB - BACKGROUND: Fibromyalgia syndrome (FMS) is a complex chronic condition that makes high demands on patients' self-management skills. Thus, patient education is considered an important component of multimodal therapy, although evidence regarding its effectiveness is scarce. The main objective of this study is to assess the effectiveness of an advanced self-management patient education program for patients with FMS as compared to usual care in the context of inpatient rehabilitation. METHODS/DESIGN: We conducted a multicenter cluster randomized controlled trial in 3 rehabilitation clinics. Clusters are groups of patients with FMS consecutively recruited within one week after admission. Patients of the intervention group receive the advanced multidisciplinary self-management patient education program (considering new knowledge on FMS, with a focus on transfer into everyday life), whereas patients in the control group receive standard patient education programs including information on FMS and coping with pain. A total of 566 patients are assessed at admission, at discharge and after 6 and 12 months, using patient reported questionnaires. Primary outcomes are patients' disease- and treatment-specific knowledge at discharge and self-management skills after 6 months. Secondary outcomes include satisfaction, attitudes and coping competences, health-promoting behavior, psychological distress, health impairment and participation. Treatment effects between groups are evaluated using multilevel regression analysis adjusting for baseline values. DISCUSSION: The study evaluates the effectiveness of a self-management patient education program for patients with FMS in the context of inpatient rehabilitation in a cluster randomized trial. Study results will show whether self-management patient education is beneficial for this group of patients. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00008782 , Registered 8 July 2015. PMID- 26842873 TI - Origin of the spin Seebeck effect in compensated ferrimagnets. AB - Magnons are the elementary excitations of a magnetically ordered system. In ferromagnets, only a single band of low-energy magnons needs to be considered, but in ferrimagnets the situation is more complex owing to different magnetic sublattices involved. In this case, low lying optical modes exist that can affect the dynamical response. Here we show that the spin Seebeck effect (SSE) is sensitive to the complexities of the magnon spectrum. The SSE is caused by thermally excited spin dynamics that are converted to a voltage by the inverse spin Hall effect at the interface to a heavy metal contact. By investigating the temperature dependence of the SSE in the ferrimagnet gadolinium iron garnet, with a magnetic compensation point near room temperature, we demonstrate that higher energy exchange magnons play a key role in the SSE. PMID- 26842874 TI - Modulation of leptin resistance by food compounds. AB - Leptin is mainly secreted by white adipose tissue and regulates energy homeostasis by inhibiting food intake and stimulating energy expenditure through its action in neuronal circuits in the brain, particularly in the hypothalamus. However, hyperleptinemia coexists with the loss of responsiveness to leptin in common obese conditions. This phenomenon has been defined as leptin resistance and the restoration of leptin sensitivity is considered to be a useful strategy to treat obesity. This review summarizes the existing literature on potentially valuable nutrients and food components to reverse leptin resistance. Notably, several food compounds, such as teasaponins, resveratrol, celastrol, caffeine, and taurine among others, are able to restore the leptin signaling in neurons by overexpressing anorexigenic peptides (proopiomelanocortin) and/or repressing orexigenic peptides (neuropeptide Y/agouti-related peptide), thus decreasing food intake. Additionally, some nutrients, such as vitamins A and D, can improve leptin transport through the blood-brain barrier. Therefore, food components can improve leptin resistance by acting at different levels of the leptin pathway; moreover, some compounds are able to target more than one feature of leptin resistance. However, systematic studies are necessary to define the actual effectiveness of each compound. PMID- 26842875 TI - Association of pollution and climate with atopic eczema in US children. AB - BACKGROUND: We sought to determine the relationship between childhood eczema, climate, and environmental pollutants. METHODS: We analyzed data from the 2007 2008 National Survey of Children's Health including a representative sample of 91,642 children age 0-17 years and the 2006-2007 Environmental Protection Agency measurements of carbon monoxide (CO), nitrate (NO3 ), nitrogen dioxide (NO2 ), organic carbon (OC), sulfate (SO3 ), sulfur dioxide (SO2 ), particulate matter <=2.5 MUm (PM-2.5) and <10 MUm (PM-10), and tropospheric ozone levels, and the National Climate Data Center measurements of relative humidity (%), issued UV index, outdoor air temperature, and precipitation levels. RESULTS: In multivariate survey logistic regression models controlling for age, sex, race/ethnicity, household income, US birthplace, and history of moving to a new location, eczema was associated with higher mean annual NO2 (p = 0.008), SO2 (p = 0.006), SO3 (p = 0.0002), arsenic (p = 0.0007), nickel (p = 0.0002), lead (p = 0.03), vanadium (p < 0.0001), and zinc (p = 0.003), but lower NO3 (p = 0.002), OC (p = 0.03), PM-2.5 (p = 0.006), cadmium (p < 0.0001), copper (p = 0.004), and potassium (p < 0.0001). In contrast, moderate-severe eczema was associated with higher NO3 (p = 0.03), OC (p = 0.008) and PM-2.5 (p = 0.01), copper (p = 0.04), lead (p = 0.008), and zinc (p = 0.01), but lower CO (p = 0.03). Principal component analysis was used and identified 4 combinations of pollutants and climate factors occurring in the USA, of which 1 was associated with higher prevalence and two were associated with lower prevalences of eczema (p < 0.05). CONCLUSIONS: Pollutants in conjunction with climate factors may differentially impact eczema prevalence and severity, some with apparent harmful effects. PMID- 26842876 TI - Aspirin Suppresses the Acquisition of Chemoresistance in Breast Cancer by Disrupting an NFkappaB-IL6 Signaling Axis Responsible for the Generation of Cancer Stem Cells. AB - Acquired chemoresistance has curtailed cancer survival since the dawn of chemotherapy. Accumulating evidence suggests a major role for cancer stem cells (CSC) in chemoresistance, although their involvement in acquired resistance is still unknown. The use of aspirin has been associated with reduced cancer risk and recurrence, suggesting that the anti-inflammatory drug may exert effects on CSCs. In this study, we investigated the contribution of CSCs to acquired chemoresistance of breast cancer and the avenues for reversing such effects with aspirin. We observed that the residual risk of recurrence was higher in breast cancer patients who had acquired chemoresistance. Treatment of preexisting CSCs with a genotoxic drug combination (5-fluorouracil, doxorubicin, and cyclophosphamide) generated an NFkappaB-IL6-dependent inflammatory environment that imparted stemness to nonstem cancer cells, induced multidrug resistance, and enhanced the migration potential of CSCs. Treatment with aspirin prior to chemotherapy suppressed the acquisition of chemoresistance by perturbing the nuclear translocation of NFkappaB in preexisting CSCs. Therefore, disruptions to the NFkappaB-IL6 feedback loop prevented CSC induction and sensitized preexisting CSCs to chemotherapy. Collectively, our findings suggest that combining aspirin and conventional chemotherapy may offer a new treatment strategy to improve recurrence-free survival of breast cancer patients. Cancer Res; 76(7); 2000-12. (c)2016 AACR. PMID- 26842877 TI - Calreticulin Expression in Human Non-Small Cell Lung Cancers Correlates with Increased Accumulation of Antitumor Immune Cells and Favorable Prognosis. AB - A high density of tumor-infiltrating mature dendritic cells (DC) and CD8(+) T cells correlates with a positive prognosis in a majority of human cancers. The recruitment of activated lymphocytes to the tumor microenvironment, primed to recognize tumor-associated antigens, can occur in response to immunogenic cell death (ICD) of tumor cells. ICD is characterized by the preapoptotic translocation of calreticulin (CRT) from the endoplasmic reticulum (ER) to the cell surface as a result of an ER stress response accompanied by the phosphorylation of eukaryotic initiation factor 2alpha (eIF2alpha). We conducted a retrospective study on two independent cohorts of patients with non-small cell lung cancer (NSCLC) to investigate the prognostic potential of CRT. We report that the level of CRT expression on tumor cells, which correlated with eIF2alpha phosphorylation, positively influenced the clinical outcome of NSCLC. High CRT expression on tumor cells was associated with a higher density of infiltrating mature DC and effector memory T-cell subsets, suggesting that CRT triggers the activation of adaptive immune responses in the tumor microenvironment. Accordingly, patients with elevated CRT expression and dense intratumoral infiltration by DC or CD8(+) T lymphocytes had the best prognosis. We conclude that CRT expression constitutes a new powerful prognostic biomarker that reflects enhanced local antitumor immune responses in the lung. Cancer Res; 76(7); 1746 56. (c)2016 AACR. PMID- 26842878 TI - Genetic Evolution during the development of an attenuated EIAV vaccine. AB - BACKGROUND: The equine infectious anemia virus (EIAV) vaccine is the only attenuated lentiviral vaccine applied on a large scale that has been shown to be effective in controlling the prevalence of EIA in China. This vaccine was developed by successive passaging of a field-isolated virulent strain in different hosts and cultivated cells. To explore the molecular basis for the phenotype alteration of this vaccine strain, we systematically analyzed its genomic evolution during vaccine development. RESULTS: Sequence analysis revealed that the genetic distance between the wild-type strain and six representative strains isolated from key development stages gradually increased with the number of passages. Env gene, but not gag and pol, showed a clear evolutionary flow similar to that of the whole genomes of different generations during the attenuation. Stable mutations were identified in multiple regions of multiple genes along with virus passaging. The adaption of the virus to the growth environment of cultured cells with accumulated genomic and genetic variations was positively correlated with the reduction in pathogenicity and rise of immunogenicity. Statistical analyses revealed significant differences in the frequency of the most stable mutations between in vivo and ex vivo-adapted strains and between virulent and attenuated strains. CONCLUSIONS: These data indicate that EIAV evolution during vaccine development generated an accumulation of mutations under the selective drive force, which helps to better understand the molecular basis of lentivirus pathogenicity and immunogenicity. PMID- 26842879 TI - Genome-wide patterns of regulatory divergence revealed by introgression lines. AB - Understanding the genetic basis for changes in transcriptional regulation is an important aspect of understanding phenotypic evolution. Using interspecific introgression lines, we infer the mechanisms of divergence in genome-wide patterns of gene expression between the nightshades Solanum pennellii and S. lycopersicum (domesticated tomato). We find that cis- and trans-regulatory changes have had qualitatively similar contributions to divergence in this clade, unlike results from other systems. Additionally, expression data from four tissues (shoot apex, ripe fruit, pollen, and seed) suggest that introgressed regions in these hybrid lines tend to be downregulated, while background (nonintrogressed) genes tend to be upregulated. Finally, we find no evidence for an association between the magnitude of differential expression in NILs and previously determined sterility phenotypes. Our results contradict previous predictions of the predominant role of cis- over trans-regulatory divergence between species, and do not support a major role for gross genome-wide misregulation in reproductive isolation between these species. PMID- 26842880 TI - Effectiveness of a Hydrogen Peroxide Mist (Trophon) System in Inactivating Healthcare Pathogens on Surface and Endocavitary Probes. PMID- 26842881 TI - A diagnostic study in patients with sciatica establishing the importance of localization of worsening of pain during coughing, sneezing and straining to assess nerve root compression on MRI. AB - PURPOSE: To test whether the localization of worsening of pain during coughing, sneezing and straining matters in the assessment of lumbosacral nerve root compression or disc herniation on MRI. METHODS: Recently the diagnostic accuracy of history items to assess disc herniation or nerve root compression on magnetic resonance imaging (MRI) was investigated. A total of 395 adult patients with severe sciatica of 6-12 weeks duration were included in this study. The question regarding the influence of coughing, sneezing and straining on the intensity of pain could be answered on a 4 point scale: no worsening of pain, worsening of back pain, worsening of leg pain, worsening of back and leg pain. Diagnostic odds ratio's (DORs) were calculated for the various dichotomization options. RESULTS: The DOR changed into significant values when the answer option was more narrowed to worsening of leg pain. The highest DOR was observed for the answer option 'worsening of leg pain' with a DOR of 2.28 (95 % CI 1.28-4.04) for the presence of nerve root compression and a DOR of 2.50 (95 % CI 1.27-4.90) for the presence of a herniated disc on MRI. CONCLUSIONS: Worsening of leg pain during coughing, sneezing or straining has a significant diagnostic value for the presence of nerve root compression and disc herniation on MRI in patients with sciatica. This study also highlights the importance of the formulation of answer options in history taking. PMID- 26842882 TI - Esophageal perforation after anterior cervical surgery: a review of the literature for over half a century with a demonstrative case and a proposed novel algorithm. AB - PURPOSE: To review relevant data for the management of esophageal perforation after anterior cervical surgery. METHODS: A case of delayed esophageal perforation after anterior cervical surgery has been presented and the relevant literature between 1958 and 2014 was reviewed. A total of 57 papers regarding esophageal perforation following anterior cervical surgery were found and utilized in this review. RESULTS: The treatment options for esophageal perforation after anterior cervical surgery were discussed and a novel management algorithm was proposed. CONCLUSION: Following anterior cervical surgery, patients should be closely followed up in the postoperative period for risk of esophageal perforation. Development of symptoms like dysphagia, pneumonia, fever, odynophagia, hoarseness, weight loss, and breathing difficulty in patients with a history of previous anterior cervical surgery should alert us for a possible esophageal injury. Review of the literature revealed that conservative treatment is advocated for early and small esophageal perforations. Surgical treatment may be considered for large esophageal defects. PMID- 26842885 TI - Agrimonia pilosa Ledeb., Cinnamomum cassia Blume, and Lonicera japonica Thunb. protect against cognitive dysfunction and energy and glucose dysregulation by reducing neuroinflammation and hippocampal insulin resistance in beta-amyloid infused rats. AB - OBJECTIVES: The water extracts of Cinnamomum cassia Blume bark (CCB; Lauraceae), Lonicera japonica Thunb. flower (LJT; Caprifoliaceae), and Agrimonia pilosa Ledeb. leaves (APL; Rosaceae) prevented amyloid-beta (25-35)-induced cell death in PC12 cells in our preliminary study. We evaluated whether long-term oral consumption of CCB, LJT, and APL improves cognitive dysfunction and glucose homeostasis in rats with experimentally induced AD-type dementia. METHODS: Male rats received hippocampal CA1 infusions of amyloid-beta (25-35, AD) or amyloid beta (35-25, non-plaque forming, normal-controls, Non-AD-CON), at a rate of 3.6 nmol/day for 14 days. AD rats were divided into four groups receiving either 2% lyophilized water extracts of CCB, LJT, or APL or 2% dextrin (AD-CON) in high-fat diets (43% energy as fat). RESULTS: Hippocampal amyloid-beta deposition, tau phosphorylation, and expressions of tumor necrosis factor (TNF)-alpha and inducible nitric oxide synthase (iNOS) (neruoinflammation markers) were increased, and insulin signaling decreased in AD-CON. CCB, LJT, and APL all prevented hippocampal amyloid-beta accumulation and enhanced hippocampal insulin signaling. CCB, LJT, and APL decreased TNF-alpha and iNOS in the hippocampus and especially APL exhibited the greatest decrease. AD-CON exhibited cognitive dysfunction in passive avoidance and water maze tests, whereas CCB, LJT, and APL protected against cognitive dysfunction, and APL was most effective and was similar to Non-AD-CON. AD-CON had less fat oxidation as an energy fuel, but it was reversed by CCB, LJT, and especially APL. APL-treated rats had less visceral fat than AD-CON rats. AD-CON rats exhibited impaired insulin sensitivity and increased insulin secretion during oral glucose tolerance test compared with Non AD-CON, but CCB and APL prevented the impairment. DISCUSSION: These results supported that APL, LJT, and CCB effectively prevent the cognitive dysfunction and the impairment of energy and glucose homeostasis induced by amyloid-beta deposition by reducing neuroinflammation and enhancing insulin signaling. APL exhibited the greatest effectiveness for improving cognitive function. PMID- 26842886 TI - Solution-State Structure and Affinities of Cyclodextrin:Fentanyl Complexes by Nuclear Magnetic Resonance Spectroscopy and Molecular Dynamics Simulation. AB - Cyclodextrins (CDs) are investigated for their ability to form inclusion complexes with the analgesic fentanyl and three similar molecules: acetylfentanyl, thiofentanyl, and acetylthiofentanyl. Stoichiometry, binding strength, and complex structure are revealed through nuclear magnetic resonance (NMR) techniques and discussed in terms of molecular dynamics (MD) simulations. It was found that beta-cyclodextrin is generally capable of forming the strongest complexes with the fentanyl panel. Two-dimensional NMR data and computational chemical calculations are used to derive solution-state structures of the complexes. Binding of the fentanyls to the CDs occurs at the amide phenyl ring, leaving the majority of the molecule solvated by water, an observation common to all four fentanyls. This finding suggests a universal binding behavior, as the vast majority of previously synthesized fentanyl analogues contain this structural moiety. This baseline study serves as the most complete work on CD:fentanyl complexes to date and provides the insights into strategies for producing future generations of designer cyclodextrins capable of stronger and more selective complexation of fentanyl and its analogues. PMID- 26842884 TI - A SPION-eicosane protective coating for water soluble capsules: Evidence for on demand drug release triggered by magnetic hyperthermia. AB - An orally-administered system for targeted, on-demand drug delivery to the gastrointestinal (GI) tract is highly desirable due to the high instances of diseases of that organ system and harsh mechanical and physical conditions any such system has to endure. To that end, we present an iron oxide nanoparticle/wax composite capsule coating using magnetic hyperthermia as a release trigger. The coating is synthesised using a simple dip-coating process from pharmaceutically approved materials using a gelatin drug capsule as a template. We show that the coating is impervious to chemical conditions within the GI tract and is completely melted within two minutes when exposed to an RF magnetic field under biologically-relevant conditions. The overall simplicity of action, durability and non-toxic and inexpensive nature of our system demonstrated herein are key for successful drug delivery systems. PMID- 26842883 TI - Activation of GPER suppresses epithelial mesenchymal transition of triple negative breast cancer cells via NF-kappaB signals. AB - The targeted therapy for triple-negative breast cancer (TNBC) is a great challenge due to our poor understanding on its molecular etiology. In the present study, our clinical data showed that the expression of G-protein coupled estrogen receptor (GPER) is negatively associated with lymph node metastasis, high-grade tumor and fibronectin (FN) expression while positively associated with the favorable outcome in 135 TNBC patients. In our experimental studies, both the in vitro migration and invasion of TNBC cells were inhibited by GPER specific agonist G-1, through the suppression of the epithelial mesenchymal transition (EMT). The G-1 treatment also reduced the phosphorylation, nuclear localization, and transcriptional activities of NF-kappaB. While over expression of NF-kappaB attenuated the action of G-1 in suppressing EMT. Our data further illustrated that the phosphorylation of GSK-3beta by PI3K/Akt and ERK1/2 mediated, at least partially, the inhibitory effect of G-1 on NF-kappaB activities. It was further confirmed in a study of MDA-MB-231 tumor xenografts in nude mice. The data showed that G-1 inhibited the in vivo growth and invasive potential of TNBC via suppression of EMT. Our present study demonstrated that an activation of GPER pathway elicits tumor suppressive actions on TNBC, and supports the use of G-1 therapeutics for TNBC metastasis. PMID- 26842888 TI - Dual Functional Nanocarrier for Cellular Imaging and Drug Delivery in Cancer Cells Based on pi-Conjugated Core and Biodegradable Polymer Arms. AB - Multipurpose polymer nanoscaffolds for cellular imaging and delivery of anticancer drug are urgently required for the cancer therapy. The present investigation reports a new polymer drug delivery concept based on biodegradable polycaprolactone (PCL) and highly luminescent pi-conjugated fluorophore as dual functional nanocarrier for cellular imaging and delivery vehicles for anticancer drug to cancer cells. To accomplish this goal, a new substituted caprolactone monomer was designed, and it was subjected to ring opening polymerization using a blue luminescent bishydroxyloligo-phenylenevinylene (OPV) fluorophore as an initiator. A series of A-B-A triblock copolymer building blocks with a fixed OPV pi-core and variable chain biodegradable PCL arm length were tailor-made. These triblocks self-assembled in organic solvents to produce well-defined helical nanofibers, whereas in water they produced spherical nanoparticles (size ~150 nm) with blue luminescence. The hydrophobic pocket of the polymer nanoparticle was found to be an efficient host for loading water insoluble anticancer drug such as doxorubicin (DOX). The photophysical studies revealed that there was no cross talking between the OPV and DOX chromophores, and their optical purity was retained in the nanoparticle assembly for cellular imaging. In vitro studies revealed that the biodegradable PCL arm was susceptible to enzymatic cleavage at the intracellular lysosomal esterase under physiological conditions to release the loaded drugs. The nascent nanoparticles were found to be nontoxic to cancer cells, whereas the DOX-loaded nanoparticles accomplished more than 80% killing in HeLa cells. Confocal microscopic analysis confirmed the cell penetrating ability of the blue luminescent polymer nanoparticles and their accumulation preferably in the cytoplasm. The DOX loaded red luminescent polymer nanoparticles were also taken up by the cells, and the drug was found to be accumulated at the perinuclear environment. The new nanocarrier approach reported in the present manuscript accomplishes both cellular imaging and delivering drugs to intracellular compartments in a single polymer system. The present investigation is one of the first examples to demonstrate the dual functional biodegradable luminescence nanocarrier concept in the literature, and the studies established this proof-of-concept in cellular imaging and drug delivery in cancer cells. PMID- 26842889 TI - UMD-Predictor: A High-Throughput Sequencing Compliant System for Pathogenicity Prediction of any Human cDNA Substitution. AB - Whole-exome sequencing (WES) is increasingly applied to research and clinical diagnosis of human diseases. It typically results in large amounts of genetic variations. Depending on the mode of inheritance, only one or two correspond to pathogenic mutations responsible for the disease and present in affected individuals. Therefore, it is crucial to filter out nonpathogenic variants and limit downstream analysis to a handful of candidate mutations. We have developed a new computational combinatorial system UMD-Predictor (http://umd-predictor.eu) to efficiently annotate cDNA substitutions of all human transcripts for their potential pathogenicity. It combines biochemical properties, impact on splicing signals, localization in protein domains, variation frequency in the global population, and conservation through the BLOSUM62 global substitution matrix and a protein-specific conservation among 100 species. We compared its accuracy with the seven most used and reliable prediction tools, using the largest reference variation datasets including more than 140,000 annotated variations. This system consistently demonstrated a better accuracy, specificity, Matthews correlation coefficient, diagnostic odds ratio, speed, and provided the shortest list of candidate mutations for WES. Webservices allow its implementation in any bioinformatics pipeline for next-generation sequencing analysis. It could benefit to a wide range of users and applications varying from gene discovery to clinical diagnosis. PMID- 26842890 TI - Tapering and discontinuation of TNF-alpha blockers without disease relapse using ultrasonography as a tool to identify patients with rheumatoid arthritis in clinical and histological remission. AB - BACKGROUND: In this study, we assessed whether clinical and ultrasonography (US) based remission could be used to select patients with rheumatoid arthritis (RA) eligible to taper and discontinue anti-TNF-alpha therapy after achievement of remission, looking at disease relapse. METHODS: Forty-two patients with RA in sustained remission who were receiving anti-TNF-alpha treatment (Disease Activity Score <1.6 at three visits 3 months apart) underwent US evaluation of synovial hypertrophy (SH) and power Doppler (PD) signal presence. Five SH+/PD- patients with RA underwent US-guided knee synovial tissue biopsy to assess histological features of residual synovitis (CD68, CD3 and CD20 immunostaining) after sustained clinical remission was achieved. All patients were enrolled to taper first then discontinue anti-TNF-alpha. They were followed every 3 months afterwards, and the relapse rate was recorded. RESULTS: Selected SH+/PD- patients showed low-grade synovitis as demonstrated by the presence of CD68+ cells in the lining layer and few infiltrating CD3+ and CD20+ cells at the time sustained clinical remission was achieved. After anti-TNF-alpha tapering, 13 patients (30.9 %) relapsed and 29 (69.1 %) SH+/PD- patients maintained disease remission after 3 months and discontinued anti-TNF-alpha treatment. Among them, 26 patients (89.7 %) maintained disease remission status after 6 months of follow-up. All patients who relapsed were retreated with the previous biologic, following the last effective therapeutic regimen, again reaching a good European League Against Rheumatism response within 3 months. CONCLUSIONS: US evaluation using PD signalling allows the identification of patients with RA in clinical and histological remission after tapering and discontinuing biologics. PMID- 26842891 TI - Same-Day Counseling: Study Protocol for the Evaluation of a New Mental Health Service. AB - BACKGROUND: Single-session counseling is being implemented across Canada to increase the accessibility and availability of mental health services. Despite increasing use, existing research on single-session counseling is sparse and has methodological limitations. In addition, some stakeholders are skeptical that this model of care can support meaningful change for clients. OBJECTIVE: The aim of this study is to evaluate a new single-session counseling program (called Same Day Counseling) offered in an outpatient community mental health clinic in Northwestern Ontario, Canada. METHODS: Clients who attend Same-Day Counseling services will be given the opportunity to participate in the program evaluation. Those who consent will complete measures before their session, after their session, and at 1-month follow-up. Data will provide information on who accesses Same-Day Counseling (eg, typical presenting problems, symptom severity), client satisfaction with services, and whether clients benefit from the services (eg, improved functioning and reduced symptom severity). RESULTS: Data collection is underway with 80 participants having completed baseline measures and 55 participants having completed follow-up measures. Data collection is expected to conclude in December 2015. CONCLUSIONS: This study is designed to contribute to the literature regarding the integration of single-session counseling into ongoing mental health services, with additional attention to methodological rigour. Our approach will help to address ongoing concerns regarding the implementation of single-session counseling, and inform health care providers and policy makers regarding the utility of this model for addressing the mental health care need of the community. PMID- 26842892 TI - Protection of scaffold protein Isu from degradation by the Lon protease Pim1 as a component of Fe-S cluster biogenesis regulation. AB - Iron-sulfur (Fe-S) clusters, essential protein cofactors, are assembled on the mitochondrial scaffold protein Isu and then transferred to recipient proteins via a multistep process in which Isu interacts sequentially with multiple protein factors. This pathway is in part regulated posttranslationally by modulation of the degradation of Isu, whose abundance increases >10-fold upon perturbation of the biogenesis process. We tested a model in which direct interaction with protein partners protects Isu from degradation by the mitochondrial Lon-type protease. Using purified components, we demonstrated that Isu is indeed a substrate of the Lon-type protease and that it is protected from degradation by Nfs1, the sulfur donor for Fe-S cluster assembly, as well as by Jac1, the J protein Hsp70 cochaperone that functions in cluster transfer from Isu. Nfs1 and Jac1 variants known to be defective in interaction with Isu were also defective in protecting Isu from degradation. Furthermore, overproduction of Jac1 protected Isu from degradation in vivo, as did Nfs1. Taken together, our results lead to a model of dynamic interplay between a protease and protein factors throughout the Fe-S cluster assembly and transfer process, leading to up-regulation of Isu levels under conditions when Fe-S cluster biogenesis does not meet cellular demands. PMID- 26842893 TI - RNase P protein subunit Rpp29 represses histone H3.3 nucleosome deposition. AB - In mammals, histone H3.3 is a critical regulator of transcription state change and heritability at both euchromatin and heterochromatin. The H3.3-specific chaperone, DAXX, together with the chromatin-remodeling factor, ATRX, regulates H3.3 deposition and transcriptional silencing at repetitive DNA, including pericentromeres and telomeres. However, the events that precede H3.3 nucleosome incorporation have not been fully elucidated. We previously showed that the DAXX ATRX-H3.3 pathway regulates a multi-copy array of an inducible transgene that can be visualized in single living cells. When this pathway is impaired, the array can be robustly activated. H3.3 is strongly recruited to the site during activation where it accumulates in a complex with transcribed sense and antisense RNA, which is distinct from the DNA/chromatin. This suggests that transcriptional events regulate H3.3 recruited to its incorporation sites. Here we report that the nucleolar RNA proteins Rpp29, fibrillarin, and RPL23a are also components of this H3.3/RNA complex. Rpp29 is a protein subunit of RNase P. Of the other subunits, POP1 and Rpp21 are similarly recruited suggesting that a variant of RNase P regulates H3.3 chromatin assembly. Rpp29 knockdown increases H3.3 chromatin incorporation, which suggests that Rpp29 represses H3.3 nucleosome deposition, a finding with implications for epigenetic regulation. PMID- 26842894 TI - Clathrin binding by the adaptor Ent5 promotes late stages of clathrin coat maturation. AB - Clathrin is a ubiquitous protein that mediates membrane traffic at many locations. To function, clathrin requires clathrin adaptors that link it to transmembrane protein cargo. In addition to this cargo selection function, many adaptors also play mechanistic roles in the formation of the transport carrier. However, the full spectrum of these mechanistic roles is poorly understood. Here we report that Ent5, an endosomal clathrin adaptor in Saccharomyces cerevisiae, regulates the behavior of clathrin coats after the recruitment of clathrin. We show that loss of Ent5 disrupts clathrin-dependent traffic and prolongs the lifespan of endosomal structures that contain clathrin and other adaptors, suggesting a defect in coat maturation at a late stage. We find that the direct binding of Ent5 with clathrin is required for its role in coat behavior and cargo traffic. Surprisingly, the interaction of Ent5 with other adaptors is dispensable for coat behavior but not cargo traffic. These findings support a model in which Ent5 clathrin binding performs a mechanistic role in coat maturation, whereas Ent5 adaptor binding promotes cargo incorporation. PMID- 26842896 TI - Allohumibacter endophyticus gen. nov., sp. nov., isolated from the root of wild Artemisia princeps (mugwort). AB - A novel actinobacterium designated strain MWE-A11T was isolated from the root of wild Artemisia princeps (mugwort). The isolate was aerobic, Gram-stain-positive and short rod-shaped, and the colonies were yellow and circular with entire margin. Strain MWE-A11T grew at 15-37 degrees C and pH 6.0-8.0. The predominant isoprenoid quinones were MK-11 and MK-10. The predominant fatty acids were anteiso-C15:0 and iso-C16:0, and the DNA G+C content was 68.8 mol%. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol and an unidentified glycolipid. The peptidoglycan contained 2,4-diaminobutyric acid as the diagnostic diamino acid, and the acyl type was glycolyl. Phylogenetic analyses based on 16S rRNA gene sequence comparisons indicated that strain MWE A11T was affiliated with the family Microbacteriaceae, and was most closely related to the type strains of Humibacter antri (96.4% 16S rRNA gene sequence similarity), Herbiconiux moechotypicola (96.3%), Leifsonia soli (96.3%), Leifsonia lichenia (96.2%), Leifsonia xyli subsp. cynodontis (96.1%), Microbacterium testaceum (96.0%) and Humibacter albus (96.0%). However, the combination of chemotaxonomic properties clearly distinguished strain MWE-A11T from the related taxa at genus level. Accordingly, Allohumibacter endophyticus gen. nov., sp. nov. is proposed to accommodate a new member of the family Microbacteriaceae. The type strain of the type species is MWE-A11T (=JCM 19371T=KCTC 29232T). PMID- 26842895 TI - The FAK-Arp2/3 interaction promotes leading edge advance and haptosensing by coupling nascent adhesions to lamellipodia actin. AB - Cell migration is initiated in response to biochemical or physical cues in the environment that promote actin-mediated lamellipodial protrusion followed by the formation of nascent integrin adhesions (NAs) within the protrusion to drive leading edge advance. Although FAK is known to be required for cell migration through effects on focal adhesions, its role in NA formation and lamellipodial dynamics is unclear. Live-cell microscopy of FAK(-/-)cells with expression of phosphorylation deficient or a FERM-domain mutant deficient in Arp2/3 binding revealed a requirement for FAK in promoting the dense formation, transient stabilization, and timely turnover of NA within lamellipodia to couple actin driven protrusion to adhesion and advance of the leading edge. Phosphorylation on Y397 of FAK promotes dense NA formation but is dispensable for transient NA stabilization and leading edge advance. In contrast, transient NA stabilization and advance of the cell edge requires FAK-Arp2/3 interaction, which promotes Arp2/3 localization to NA and reduces FAK activity. Haptosensing of extracellular matrix (ECM) concentration during migration requires the interaction between FAK and Arp2/3, whereas FAK phosphorylation modulates mechanosensing of ECM stiffness during spreading. Taken together, our results show that mechanistically separable functions of FAK in NA are required for cells to distinguish distinct properties of their environment during migration. PMID- 26842897 TI - [Patients with ICD-10 disorders F3 and F4 in psychiatric and psychosomatic in patient units - who is treated where? : Allocation features from the PfAD study]. AB - BACKGROUND: In Germany, in-patient treatment of patients with depressive, neurotic, anxiety, and somatoform disorders (ICD-10 F3, F4) is carried out in different settings in psychiatry and psychosomatics. Which patient characteristics determine referral to one or the other specialty is a crucial question in mental health policy and is a matter of ongoing controversy. However, comparative data on patient populations are widely lacking. METHODS: In the study of Treatment Pathways of Patients with Anxiety and Depression (PfAD study), a total of 320 patients with ICD-10 F3/F4 clinical diagnoses were consecutively recruited from four treatment settings (psychiatric depression ward, psychiatric crisis intervention ward, psychiatric day hospitals, or psychosomatic hospital units; 80 participants per setting) and investigated. RESULTS: In all treatment settings, patients with considerable severity of illness and chronicity were treated. Female gender, higher education, and higher income predicted referral to psychosomatic units; male gender, transfer from another hospital or emergency hospitalization, co-morbidity with a personality disorder, higher general psychiatric co-morbidity, and danger to self at admission predicted referral to psychiatric unit. Patients in psychosomatic units had neither more psychosomatic disorders nor more somatic problems. DISCUSSION: There is considerable overlap between the clientele of psychiatric and psychosomatic units. Referral and allocation appears to be determined by aspects of severity and social status. PMID- 26842899 TI - [Normative definition of staff requirement for a guideline-adherent inpatient qualified detoxification treatment in alcohol dependence]. AB - The central element of the "qualified withdrawal treatment" of alcohol dependence is - in addition to physical withdrawal treatment - psychotherapy. The treatment of the underlying addictive disorder that is displayed by intoxication, harmful behaviour and withdrawal symptoms is only possible with a combination of somatic and psychotherapeutic treatment elements. The successfully established multimodal therapy of the "qualified alcohol withdrawal treatment", postulated in the current S3-Treatment Guidelines, requires a multi-disciplinary treatment team with psychotherapeutic competence. The aim of the present work is to calculate the normative staff requirement of a guideline-based 21-day qualified withdrawal treatment and to compare the result with the staffing regulations of the German Institute for Hospital Reimbursement. The present data support the hypothesis that even in the case of a hundred per cent implementation of these data, adequate therapy of alcohol-related disorders, according to the guidelines, is not feasible. This has to be considered when further developing the finance compensation system based on the described superseded elements of the German Institute for Hospital Reimbursement. PMID- 26842898 TI - [Critical illness polyneuropathy and myopathy as neurological complications of sepsis]. AB - Intensive care unit acquired weakness (ICUAW) is a frequent and severe complication of intensive care management. Within ICUAW critical illness polyneuropathy (CIP) and myopathy (CIM) can be differentiated. The major symptom of ICUAW is progressive quadriparesis, which makes weaning from the respirator more difficult, can appear early after admission to an ICU and can often be detected several months after discharge from the ICU. The pathophysiology of ICUAW is multifactorial and complex. Potential therapeutic approaches are the early and sufficient therapy of mulitorgan dysfunction, optimal control of glucose levels as well as early and intensive physiotherapy. This review article discusses the data on incidence, pathophysiology, diagnostic approaches and prognosis of ICUAW. PMID- 26842900 TI - [Lumbar back pain in patients with Parkinson's disease]. AB - BACKGROUND: Lumbar back pain is a frequent symptom in patients with advanced Parkinson's disease. We examined the effect of modification of the dopaminergic medication, x-ray-controlled lumbar spine injections and analgesics combined with physiotherapy. METHODS: The data from 50 patients with Parkinson's disease and lumbar back pain were retrospectively analyzed. A structured L-dopa test was performed with all patients, whereby the pain intensity and mobility were monitored before and after the administration of L-dopa. Dopaminergic medication was adjusted in patients who reported either a reduction in pain intensity (> 20%) and/or an improvement of measured mobility and X-ray controlled lumbar spine injections were conducted in patients who reported persistent pain. Analgesics were introduced or dosages were raised in patients who had already received lumbar spine injections and continued to report pain. All patients participated in a daily physiotherapy program. RESULTS: In the L-dopa test an improvement of mobility could be demonstrated in 40 patients and reduced pain intensity in 21 patients. In 37 patients with a positive L-dopa test the dopaminergic medication was adjusted. In 12 of these patients (24%) a decrease of pain intensity could be observed. Due to persisting back pain in 30 patients lumbar spine injections were conducted. Of these patients 17 (34%) had pain improvement. In 20 patients analgesics were applied and induced pain relief in 15 patients (30%). Overall 44 patients (88%) had an improvement in pain. DISCUSSION: Even in cases of severe lumbar spine pathology adjustment of dopaminergic medication should be tested in all patients with Parkinson's disease and lumbar back pain. In patients with persistent pain facet joint injections as well as analgesics may be helpful and should be tested according to the predominant pain characteristics. PMID- 26842903 TI - Beyond Biomedicine: Relationships and Care in Tuberculosis Prevention. AB - With attention to the experiences, agency, and rights of tuberculosis (TB) patients, this symposium on TB and ethics brings together a range of different voices from the social sciences and humanities. To develop fresh insights and new approaches to TB care and prevention, it is important to incorporate diverse perspectives from outside the strictly biomedical model. In the articles presented in this issue of the Journal of Bioethical Inquiry, clinical experience is married with historical and cultural context, ethical concerns are brought to bear on global health, and structural analyses shed light upon the lived experience of people living with TB. The relational and reciprocal dimensions of care feature strongly in these discussions, which serve as a poignant reminder that behind each of the yearly deaths from TB is a deeply personal story. No single discipline holds a monopoly on how to care for each of these people, but strong cases are made for support from mental health and social workers in addressing the kaleidoscope of needs in TB prevention. As the World Health Organization moves towards the goal of eliminating TB globally by 2050, attending to the needs of TB patients serves global interests to lower disease burden and to develop better integrated communities worldwide. PMID- 26842902 TI - The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE. Design, rationale, and clinical implications. AB - Hospital-associated venous thromboembolism (VTE) is a leading cause of premature death and disability worldwide. Evidence-based guidelines recommend that anticoagulant thromboprophylaxis be given to hospitalised medical patients at risk of VTE, but suggest against routine use of thromboprophylaxis beyond the hospital stay. The MARINER study is a randomised, double-blind, placebo controlled trial to evaluate the efficacy and safety of thromboprophylaxis using rivaroxaban, begun at hospital discharge and continued for 45 days, for preventing symptomatic VTE in high-risk medical patients. Eligible patients are identified using the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE VTE) risk score, combined with a laboratory test, D dimer. The rivaroxaban regimen is 10 mg once daily for patients with CrCl >= 50 ml/min, or 7.5 mg once daily for patients with CrCl >= 30 ml/min and < 50 ml/min. The primary efficacy outcome is the composite of symptomatic VTE (lower extremity deep-vein thrombosis and non-fatal pulmonary embolism) and VTE-related death. The principal safety outcome is major bleeding. A blinded clinical events committee adjudicates all suspected outcome events. The sample size is event-driven with an estimated total of 8,000 patients to acquire 161 primary outcome events. Study design features that distinguish MARINER from previous and ongoing thromboprophylaxis trials in medically ill patients are: (i) use of a validated risk assessment model (IMPROVE VTE) and D-dimer determination for identifying eligible patients at high risk of VTE, (ii) randomisation at the time of hospital discharge, (iii) a 45-day treatment period and (iv) restriction of the primary efficacy outcome to symptomatic VTE events. PMID- 26842904 TI - The Extension of Belgium's Euthanasia Law to Include Competent Minors. AB - Following considerable debate, the practice of euthanasia was legalized in Belgium in 2002, thereby making Belgium one of the few places in the world where this practice is legal. In 2014 the law was amended for the first time. The 2014 amendment makes euthanasia legally possible for all minors who repeatedly and voluntarily request euthanasia and who are judged to possess "capacity of discernment" (regardless of their biological age), as well as fulfil a number of other criteria of due care. This extension of the 2002 euthanasia law generated a lot of national and international debate and has been applauded by many and heavily criticized by others. This evolution is clearly of interest to end-of life debates in the entire world. This paper will therefore describe how this amendment came to get passed using official documents from Belgium's Senate and Chamber of Representatives where this amendment was discussed and subsequently passed. Next, some of the most commonly given arguments in favour of the law are identified, as well as the arguments most often voiced against the amendment. All these arguments will be expanded upon and it will be examined whether they hold up to ethical scrutiny. Analysing the official documents and identifying the most commonly voiced arguments gives valuable insight into how Belgium came to amend its euthanasia law and why it did so in 2014. It also becomes clear that although the current amendment is often seen as far-reaching, more radical ideas were proposed during the drafting of the law. Also, in analysing those arguments in favour of the amendment and those against, it is clear that the validity of some of these is questionable. PMID- 26842901 TI - Role of TRP ion channels in cancer and tumorigenesis. AB - Transient receptor potential (TRP) channels are recently identified proteins that form a versatile family of ion channels, the majority of which are calcium permeable and exhibit complex regulatory patterns with sensitivity to multiple environmental factors. While this sensitivity has captured early attention, leading to recognition of TRP channels as environmental and chemical sensors, many later studies concentrated on the regulation of intracellular calcium by TRP channels. Due to mutations, dysregulation of ion channel gating or expression levels, normal spatiotemporal patterns of local Ca(2+) distribution become distorted. This causes deregulation of downstream effectors sensitive to changes in Ca(2+) homeostasis that, in turn, promotes pathophysiological cancer hallmarks, such as enhanced survival, proliferation and invasion. These observations give rise to the appreciation of the important contributions that TRP channels make to many cellular processes controlling cell fate and positioning these channels as important players in cancer regulation. This review discusses the accumulated scientific knowledge focused on TRP channel involvement in regulation of cell fate in various transformed tissues. PMID- 26842906 TI - Visualizing tropoelastin in a long-term human elastic fibre cell culture model. AB - Elastin is an essential protein found in a variety of tissues where resilience and flexibility are needed, such as the skin and the heart. When aiming to engineer suitable implants, elastic fibres are needed to allow adequate tissue renewal. However, the visualization of human elastogenesis remains in the dark. To date, the visualization of human tropoelastin (TE) production in a human cell context and its fibre assembly under live cell conditions has not been achieved. Here, we present a long-term cell culture model of human dermal fibroblasts expressing fluorescence-labelled human TE. We employed a lentiviral system to stably overexpress Citrine-labelled TE to build a fluorescent fibre network. Using immunofluorescence, we confirmed the functionality of the Citrine-tagged TE. Furthermore, we visualized the fibre assembly over the course of several days using confocal microscopy. Applying super resolution microscopy, we were able to investigate the inner structure of the elastin-fibrillin-1 fibre network. Future investigations will allow the tracking of TE produced under various conditions. In tissue engineering applications the fluorescent fibre network can be visualized under various conditions or it serves as a tool for investigating fibre degradation processes in disease-in-a-dish-models. PMID- 26842905 TI - Spinal inhibition and motor function in adults with spastic cerebral palsy. AB - KEY POINTS: Abnormal activation of motoneurons in the spinal cord by sensory pathways is thought to contribute to impaired movement control and spasticity in individuals with cerebral palsy. Here we use single motor unit recordings to show how individual motoneurons in the spinal cord respond to sensory inputs in a group of participants with cerebral palsy having different degrees of motor dysfunction. In participants who had problems walking independently and required assistive devices such as wheelchairs, sensory pathways only excited motoneurons in the spinal cord. In contrast, in participants with cerebral palsy who walked independently for long distances, sensory inputs both inhibited and excited motoneurons in the spinal cord, similar to what we found in uninjured control participants. These findings demonstrate that in individuals with severe cerebral palsy, inhibitory control of motoneurons from sensory pathways is reduced and may contribute to motor dysfunction and spasticity. ABSTRACT: Reduced inhibition of spinal motoneurons by sensory pathways may contribute to heightened reflex activity, spasticity and impaired motor function in individuals with cerebral palsy (CP). To measure if the activation of inhibitory post-synaptic potentials (IPSPs) by sensory inputs is reduced in CP, the tonic discharge rate of single motor units from the soleus muscle was plotted time-locked to the occurrence of a sensory stimulation to produce peri-stimulus frequencygrams (PSFs). Stimulation to the medial arch of the foot was used to activate cutaneomuscular afferents in 17 adults with bilateral spastic CP and 15 neurologically intact (NI) peers. Evidence of IPSP activation from the PSF profiles, namely a marked pause or reduction in motor unit firing rates at the onset of the cutaneomuscular reflex, was found in all NI participants but in only half of participants with CP. In the other half of the participants with CP, stimulation of cutaneomuscular afferents produced a PSF profile indicative of a pure excitatory post-synaptic potential, with firing rates increasing above the mean pre-stimulus rate for 300 ms or more. The amplitude of motoneuron inhibition during the period of IPSP activation, as measured from the surface EMG, was less in participants with poor motor function as evaluated with the Gross Motor Functional Classification System (r = 0.72, P < 0.001) and the Functional Mobility Scale (r = -0.82, P < 0.001). These findings demonstrate that in individuals with CP, reduced activation of motoneuron IPSPs by sensory inputs is associated with reduced motor function and may contribute to enhanced reflexes and spasticity in CP. PMID- 26842908 TI - Protective Effect of Sinapine against Hydroxyl Radical-Induced Damage to Mesenchymal Stem Cells and Possible Mechanisms. AB - As a phenolic alkaloid occurring in Cruciferous plants, sinapine was observed to protect mesenchymal stem cells (MSCs) against .OH-induced damage in this study. It was also found to prevent DNA from damage, to scavenge various free radicals (.OH, .O2(-), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid diammonium salt) (ABTS)(+.), and 1,1-diphenyl-2-picrylhydrazyl radical (DPPH.)), and to reduce Cu(2+) to Cu(+). To further explore the mechanism, the end-product of sinapine reaction with DPPH. was determined using HPLC-electrospray ionization (ESI)-MS/MS and HPLC-diode array detector (DAD). Four molecular ion peaks (m/z 701, 702, 703, and 351) in HPLC-ESI-MS/MS analysis indicated a radical adduct formation (RAF) pathway; while a bathochromic shift (lambda(max) 334->475 nm) in HPLC-DAD indicated the formation of quinone as the oxidized product of the phenolic -OH group. Based on these results, it may be concluded that, (i) sinapine can effectively protect against .OH-induced damage to DNA and MSCs; such protective effect may provide evidence for a potential role for sinapine in MSC transplantation therapy, and be responsible for the beneficial effects of Cruciferous plants. (ii) The possible mechanism for sinapine to protect against .OH-induced oxidative damage is radical-scavenging, which is thought to be via hydrogen atom (H.) transfer (HAT) (or sequential electron (e) proton transfer (SEPT))->RAF pathways. PMID- 26842907 TI - Development of novel FP-based probes for live-cell imaging of nitric oxide dynamics. AB - Nitric oxide () is a free radical with a wide range of biological effects, but practically impossible to visualize in single cells. Here we report the development of novel multicoloured fluorescent quenching-based probes by fusing a bacteria-derived -binding domain close to distinct fluorescent protein variants. These genetically encoded probes, referred to as geNOps, provide a selective, specific and real-time read-out of cellular dynamics and, hence, open a new era of bioimaging. The combination of geNOps with a Ca(2+) sensor allowed us to visualize and Ca(2+) signals simultaneously in single endothelial cells. Moreover, targeting of the probes was used to detect signals within mitochondria. The geNOps are useful new tools to further investigate and understand the complex patterns of signalling on the single (sub)cellular level. PMID- 26842909 TI - Global prevalence of pre-existing HCV variants resistant to direct-acting antiviral agents (DAAs): mining the GenBank HCV genome data. AB - Direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) proteins open a whole new era for anti-HCV therapy, but DAA resistance associated variants (RAVs) could jeopardize the effectiveness of DAAs. We reported the global prevalence of DAA RAVs using published GenBank data. 58.7% of sequences (854/1455) harbored at least one dominant resistance variant and the highest RAV frequency occurred in Asia (74.1%), followed by Africa (71.9%), America (53.5%) and Europe (51.4%). The highest RAV frequency was observed in genotype (GT) 6 sequences (99%), followed by GT2 (87.9%), GT4 (85.5%), GT1a (56%), GT3 (50.0%) and GT1b (34.3%). Furthermore, 40.0% and 29.6% of sequences were detected RAVs of non-structural (NS) 5A inhibitors and NS3 protease inhibitors, respectively. However, RAVs to NS5B nucleo(t)ide inhibitor (NI) and NI-based combinations were uncommon (<4% of sequences). As expected, combinations of multiple RAVs to the IFN-free regimens recommended by current guidelines were rarely detected (0.2% 2.0%). Our results showed that the overall global prevalence of DAA RAVs was high irrespective of geography or genotype. However, the NI-based multi-DAA regimens had a low RAV prevalence, suggesting that these regimens are the most promising strategies for cure of the long-term HCV infection. PMID- 26842912 TI - Immune regulation of canine tumour and macrophage PD-L1 expression. AB - Expression of programmed cell death receptor ligand 1 (PD-L1) on tumor cells has been associated with immune escape in human and murine cancers, but little is known regarding the immune regulation of PD-L1 expression by tumor cells and tumor-infiltrating macrophages in dogs. Therefore, 14 canine tumor cell lines, as well as primary cultures of canine monocytes and macrophages, were evaluated for constitutive PD-L1 expression and for responsiveness to immune stimuli. We found that PD-L1 was expressed constitutively on all canine tumor cell lines evaluated, although the levels of basal expression were very variable. Significant upregulation of PD-L1 expression by all tumor cell lines was observed following IFN-gamma exposure and by exposure to a TLR3 ligand. Canine monocytes and monocyte-derived macrophages did not express PD-L1 constitutively, but did significantly upregulate expression following treatment with IFN-gamma. These findings suggest that most canine tumors express PD-L1 constitutively and that both innate and adaptive immune stimuli can further upregulate PD-L1 expression. Therefore the upregulation of PD-L1 expression by tumor cells and by tumor infiltrating macrophages in response to cytokines such as IFN-gamma may represent an important mechanism of tumor-mediated T-cell suppression in dogs as well as in humans. PMID- 26842910 TI - MiR-302a/b/c/d cooperatively sensitizes breast cancer cells to adriamycin via suppressing P-glycoprotein(P-gp) by targeting MAP/ERK kinase kinase 1 (MEKK1). AB - BACKGROUND: The importance of individual microRNAs (miRNAs) in tumor has been established in different cancers. However, their association with tumor chemoresistance has not been fully understood. Previously, we found two novel MDR associated microRNAs (miRNAs). In this report, we investigated the combined effects of miRNA gene cluster in chemoresistance of breast cancer. METHODS: This study was performed in two different breast cancer cell lines (MCF-7 and MCF 7/ADR). The levels of miRNAs and mRNA expression were determined by using Quantitative Real-Time PCR. Western blotting was used to detect the levels of protein molecules. Cell viability was assessed by MTS assay. Bioinformatics and Luciferase reporter assay was performed to examine miRNA binding to the 3'-UTR of target genes. RESULTS: The miR-302S family including miR-302a, miR-302b, miR 302c, and miR-302d was significantly down-regulated in P-glycoprotein (P-gp) overexpressing MCF-7/ADR cells. Overexpression of miR-302 increased intracellular accumulation of ADR and sensitized breast cancer cells to ADR. Most importantly, miR-302S produced stronger effects than each individual member alone. The four miRNAs cooperatively downregulate P-gp expression in regulating drug sensitivity. However, our results showed that the suppression of P-gp expression by miR-302 is not through typical miRNA-mediated mRNA degradation but at the level of protein and transcription. Further studies identified MAP/ERK kinase kinase 1 (MEKK1) as a direct and functional target of miR-302. miR-302 showed combinatorial effects on MKEE1 repression and MEKK1-mediated ERK pathway. The suppression of P-gp by miR-302 was reversed by MEKK1 overexpression. CONCLUSION: Our results indicate that miR-302 cooperatively sensitizes breast cancer cells to adriamycin via suppressing P-glycoprotein by targeting MEKK1 of ERK pathway. miR-302 gene cluster may be a potential target for reversing P-gp-mediated chemoresistance in breast cancer. PMID- 26842913 TI - Breakfast consumption and adiposity among children and adolescents: an updated review of the literature. AB - BACKGROUND: Breakfast consumption has been associated with reduced risk of overweight and obesity among children, but previous evidence reviews fail to confirm a causal relationship. OBJECTIVES: To review recent literature on breakfast consumption and adiposity among children and discuss potential underlying mechanisms. METHODS: A comprehensive literature search of studies published since the 2010 US National Evidence Library review (January 2010 January 2015) was conducted. RESULTS: Twelve studies met inclusion criteria. All were conducted in industrialized countries: six in Europe, four in the USA, one in China and one in Australia. Ten of the studies used observational longitudinal designs, with follow-up periods ranging from 1 to 27 years (median: 3, mean: 7.4); of these, eight reported inverse associations between breakfast consumption and excess adiposity, while two found no association. The other studies (1 case control, 1 experimental) each reported a protective effect of breakfast consumption on overweight and obesity among children. CONCLUSIONS: Findings corroborate results from previous reviews, adding support for a possible, protective role for breakfast consumption in preventing excess adiposity during childhood and adolescence. However, drawing a causal conclusion from the collective evidence is curtailed by methodological limitations and inconsistencies, including study design, follow-up duration and frequency, exposure and outcome assessment, as well as limited consideration of confounding, mediating and effect-modifying variables. More rigorous study designs employing valid and standardized measurement of relevant variables are needed. PMID- 26842914 TI - Side-Effects of Glyphosate to the Parasitoid Telenomus remus Nixon (Hymenoptera: Platygastridae). AB - The aim of this study was to compare the side-effects of glyphosate to the parasitoid Telenomus remus Nixon (Hymenoptera: Platygastridae) when parasitoids were exposed to this chemical at the pupal (inside host eggs) and adult stages. Bioassays were conducted under laboratory conditions according to the International Organization for Biological Control (IOBC) standard methods for testing side-effects of pesticides to egg parasitoids. Different glyphosate-based pesticides (Roundup Original(r), Roundup Ready(r), Roundup Transorb(r), Roundup WG(r), and Zapp Qi(r)) were tested at the same acid equivalent concentration. Treatments were classified following the IOBC toxicity categories as (1) harmless, (2) slightly harmful, (3) moderately harmful, and (4) harmful. When tested against T. remus adults, Roundup Original(r), Roundup Ready(r), Roundup Transorb(r), and Roundup WG(r) reduced parasitism 2 days after parasitoid emergence, being classified as slightly harmful. Differently, when tested against T. remus pupae, all tested glyphosate-based products did not differ in their lethal effect and therefore did not reduce T. remus adult emergence or parasitism capacity, being classified as harmless. However, differences on sublethal toxicity were found. Parasitism of individuals emerging from parasitized eggs sprayed at the pupal stage of T. remus with Zapp Qi(r) was lower compared to control, but parasitism was still higher than 66%, and therefore, Zapp Qi(r) was still classified as harmless. In conclusion, all tested glyphosate-based products can be used in agriculture without negative impact to T. remus as none was classified as harmful or moderately harmful to this parasitoid when exposure occurred at the pupal or adult stages. PMID- 26842915 TI - Linking suckling biomechanics to the development of the palate. AB - Skulls are amongst the most informative documents of evolutionary history but a complex geometry, coupled with composite material properties and complicated biomechanics, have made it particularly challenging to identify mechanical principles guiding the skull's morphogenesis. Despite this challenge, multiple lines of evidence, for example the relationship between masticatory function and the evolution of jaw shape, nonetheless suggest that mechanobiology plays a major role in skull morphogenesis. To begin to tackle this persistent challenge, cellular, molecular and tissue-level analyses of the developing mouse palate were coupled with finite element modeling to demonstrate that patterns of strain created by mammalian-specific oral behaviors produce complementary patterns of chondrogenic gene expression in an initially homogeneous population of cranial neural crest cells. Neural crest cells change from an osteogenic to a chondrogenic fate, leading to the materialization of cartilaginous growth plate like structures in the palatal midline. These growth plates contribute to lateral expansion of the head but are transient structures; when the strain patterns associated with suckling dissipate at weaning, the growth plates disappear and the palate ossifies. Thus, mechanical cues such as strain appear to co-regulate cell fate specification and ultimately, help drive large-scale morphogenetic changes in head shape. PMID- 26842917 TI - JWH-133, a Selective Cannabinoid CB2 Receptor Agonist, Exerts Toxic Effects on Neuroblastoma SH-SY5Y Cells. AB - Endocannabinoid system plays an important role in the regulation of diverse physiological functions. Although cannabinoid type 2 receptors (CB2) are involved in the modulation of immune system in peripheral tissues, recent findings demonstrated that they are also expressed in the central nervous system and could constitute a new target for the treatment of neurodegenerative disorders. At present, very little is known about the potential effects of CB2-mimetic drugs on neuronal cells. This study aimed to examine whether JWH-133, a selective CB2 receptor agonist, affects the survival of SH-SY5Y neuroblastoma cell line, a widely used experimental in vitro model to study mechanisms of toxicity and protection in nigral dopaminergic neurons. Cell viability was assessed using two complementary methods: MTT test measuring mitochondrial activity and LDHe test indicating disruption of cell membrane integrity. In addition, cell proliferation was measured using BrdU incorporation assay. JWH-133 (10-40 MUM) induced a concentration-dependent decrease of SH-SY5Y cell viability and proliferation rate. Using AM-630, a reverse agonist of CB2 receptors, as well as Z-VAD-FMK, a pan-caspase inhibitor, we demonstrated that the cytotoxic effect of JWH-133 presumably was not mediated by activation of CB2 receptors or by caspase pathway. Results of this work suggest that agonists of CB2 receptors when administered in multiple/high doses may induce neuronal damage. PMID- 26842918 TI - Temperature-controlled spin filter and spin valve based on Fe-doped monolayer MoS2. AB - The thermal transport properties of an iron-doped molybdenum disulfide system were explored theoretically using the density functional theory calculations combined with the Keldysh non-equilibrium Green's function approach. The results indicate that a perfect spin filtering effect and spin Seebeck effect are induced thermally. Excellently, there exists thermal colossal magnetoresistances, which exhibit a transition between positive and negative that can be tuned using temperature. These features were elucidated using the band structures of the electrodes and the transmission function together with current spectra. Our findings may be helpful in the design of highly efficient spin caloritronic devices. PMID- 26842916 TI - The Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway as a Discovery Target in Stroke. AB - Protein kinases are critical modulators of a variety of intracellular and extracellular signal transduction pathways, and abnormal phosphorylation events can contribute to disease progression in a variety of diseases. As a result, protein kinases have emerged as important new drug targets for small molecule therapeutics. The mitogen-activated protein kinase (MAPK) signaling pathway transmits signals from the cell membrane to the nucleus in response to a variety of different stimuli. Because this pathway controls a broad spectrum of cellular processes, including growth, inflammation, and stress responses, it is accepted as a therapeutic target for cancer and peripheral inflammatory disorders. There is also increasing evidence that MAPK is an important regulator of ischemic and hemorrhagic cerebral vascular disease, raising the possibility that it might be a drug discovery target for stroke. In this review, we discuss the MAPK signaling pathway in association with its activation in stroke-induced brain injury. PMID- 26842919 TI - Effects of deviation from focal plane on lesion geometry for ablative fractional photothermolysis. AB - BACKGROUND AND OBJECTIVE: Fractional Photothermolysis (FP) is a method of skin treatment that generates a thermal damage pattern consisting of multiple columns of thermal damage, also known as microscopic treatment zones (MTZs). They are very small in diameter and are generated by application of highly focused laser beams. In order to obtain the smallest spot size, the treatment should be performed in the focal plane. Any deviation from the focal plane (DFP) results in an increase of spot size. FP devices typically utilize distance holders in order to facilitate exposures at this specific location. In spite of the use of distance holders, DFP can occur. In particular, variations of contact pressure to the skin surface and anatomical treatment areas of high surface curvature may be prone to DFP during FP treatments. The impact of such distance variation on lesion geometry, such as depth and diameter of the thermal injury, has not previously been evaluated. The objective of this study was to investigate the relation between DFP and the resulting lesion geometry for a selected ablative fractional device. MATERIAL AND METHODS: A handpiece of an ablative fractional laser (DeepFX, UltraPulse Encore, Lumenis, Yokneam, Israel) was mounted to a rigid stand. Full thickness human skin obtained from abdominoplasty was mounted to a separate stand perpendicular to the handpiece. The tissue stand allowed the distance between the handpiece and the tissue to be adjusted to produce a variation up to +/-3 mm from the focal plane. A 1 * 1 cm(2) scanning area of 169 MTZs, 50 mJ energy per MTZ, 120 MUm nominal spot size, was applied at -3, -2, -1, 0, +1, +2, and +3 mm deviated from the focal plane. Minus (-) and plus (+) signs indicate decreasing and increasing distance between the handpiece and the tissue, respectively. Depth and diameter of the laser induced tissue lesions were assessed and quantified. RESULTS: DFPs produced a significant alteration of the lesion geometry. DFPs of -3, -2, -1, 0, +1, +2, +3 mm resulted in average lesion depths of 1,020 (-40%), 1,180 (-31%), 1,400 (-18%), 1,700 (0%), 1,620 (-5%), 780 (-55%), 680 (-60%) um, and average lesion diameters of 314 (+26%), 311 (+25%), 273 (+10%), 248 (0%), 256 (+3%), 316 (+27%), 359 (+44%) um, respectively. The underlined values represent the focal plane. The percentage changes relative to values at focal plane are in parentheses. CONCLUSIONS: A relatively minor DFP has a marked impact on the thermal injury profile, including lesion depth and diameter, of the laser-exposed tissue. Such marked changes of the thermal injury profile might affect the wound healing, safety, and efficacy of ablative fractional resurfacing procedures. Clinicians should carefully maintain the focal plane during ablative fractional treatment for reproducible results. The presented data are device specific and the clinical impact of such alteration of thermal injury profile warrants further investigation. Lasers Surg. Med. 48:555 561, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26842921 TI - The effects of an ionic liquid on unimolecular substitution processes: the importance of the extent of transition state solvation. AB - The reaction of bromodiphenylmethane and 3-chloropyridine, which proceeds concurrently through both unimolecular and bimolecular mechanisms, was examined in mixtures of acetonitrile and an ionic liquid. As predicted, the bimolecular rate constant (k2) gradually increased as the amount of ionic liquid in the reaction mixture increased, as a result of a minor enthalpic cost offset by a more significant entropic benefit. Addition of an ionic liquid had a substantial effect on the unimolecular rate constant (k1) of the reaction, with at least a 5 fold rate enhancement relative to acetonitrile, which was found to be due to a significant decrease in the enthalpy of activation, partially offset by the associated decrease in the entropy of activation. This is in contrast to the effects seen previously for aliphatic carbocation formation, where the entropic cost dominated reaction outcome. This change is attributed to a lessened ionic liquid-transition state interaction, as the incipient charges in the transition state were delocalized across the neighbouring pi systems. By varying the mole fraction of ionic liquid in the reaction mixture the ratio between k1 and k2 could be altered, highlighting the potential to use ionic liquids to control which pathway a reaction proceeds through. PMID- 26842922 TI - Use of a new intra-ocular spectral domain optical coherence tomography in vitreoretinal surgery. AB - PURPOSE: To describe the use of a novel intra-ocular side-scanning probe enabling the acquisition of spectral-domain optical coherence tomography (SD-OCT) images during surgery in a series of patients with complex forms of retinal detachment. METHODS: A 23-gauge, side-scanning SD-OCT probe (C7 System; LightLab Imaging, Inc/St Jude Medical, St. Paul, MN, USA) in a 20-gauge catheter, was used to acquire the intra-operative OCT images in seven patients with vitreoretinal diseases. Twenty-five gauge pars plana vitrectomy (PPV) was performed in every patient in a standard fashion. After enlarging the temporal sclerotomy to a 20 gauge port, all the patients were scanned with intra-ocular side-scanning SD-OCT, during different steps of the surgery based on surgeon needs. Scans were recorded real time and directly evaluated on a screen during surgery. Optical coherence tomography (OCT) scans were judged beneficial when they would recognize structures otherwise not seen on biomicroscopy. RESULTS: The intra-ocular SD-OCT has been helpful in acquiring extra information during vitreoretinal surgery such as the detection of the presence of otherwise invisible membranes (epiretinal membrane, subretinal membrane), the location of small tears and the identification of the retinal plane under suboptimal conditions for visualization. CONCLUSION: The use of an intra-ocular SD-OCT can expand upon visual cues during surgery, helping in the decision-making process and allowing additional deliberate surgical manoeuvres aimed at improving surgical outcomes. PMID- 26842920 TI - Growth Charts for Prader-Willi Syndrome During Growth Hormone Treatment. AB - The purpose of the current study was to develop syndrome-specific standardized growth curves for growth hormone-treated Prader-Willi syndrome (PWS) individuals aged 0 to 18 years. Anthropometric growth-related measures were obtained on 171 subjects with PWS who were treated with growth hormone for at least 40% of their lifespan. They had no history of scoliosis. PWS standardized growth curves were developed for 7 percentile ranges using the LMS method for weight, height, head circumference, weight/length, and BMI along with normative 3rd, 50th, and 97th percentiles plotted using control data from the literature and growth databases. Percentiles were plotted on growth charts for comparison purposes. Growth hormone treatment appears to normalize stature and markedly improves weight in PWS compared with standardized curves for non-growth hormone-treated PWS individuals. Growth chart implications and recommended usage are discussed. PMID- 26842923 TI - The interaction of hepatoma-derived growth factor and beta-catenin promotes tumorigenesis of synovial sarcoma. AB - To clarify the clinicopathological and biological role of hepatoma-derived growth factor (HDGF) and beta-catenin in synovial sarcoma. Our results showed that histological type and HDGF/beta-catenin expression were the two important independent prognostic factors for overall survival in synovial sarcoma patients. HDGF knockdown dramatically inhibited cellular proliferation, colony formation, and migration but induced G1 phase arrest and apoptosis in SW982 cells. Recombinant HDGF enhanced synovial sarcoma cell growth and partially retrieved the cell growth suppression in SW982 cells upon HDGF knockdown. HDGF knockdown dramatically suppressed beta-catenin and its downstream gene expression in SW982 cells. Intriguingly, beta-catenin knockdown dramatically suppressed HDGF expression in SW982 cells. A direct interaction of HDGF and beta-catenin was found in SW982 cells. Three HDGF-binding elements in beta-catenin promoter were found and specific for transcriptional activation of beta-catenin in SW982 cells. In conclusion, our findings first indicate that the interaction of HDGF and beta catenin may play a crucial role in tumorigenesis of synovial sarcoma. PMID- 26842924 TI - Segmental distribution of some common molecular markers for colorectal cancer (CRC): influencing factors and potential implications. AB - Proximal and distal colorectal cancers (CRCs) are regarded as distinct disease entities, evolving through different genetic pathways and showing multiple clinicopathological and molecular differences. Segmental distribution of some common markers (e.g., KRAS, EGFR, Ki-67, Bcl-2, COX-2) is clinically important, potentially affecting their prognostic or predictive value. However, this distribution is influenced by a variety of factors such as the anatomical overlap of tumorigenic molecular events, associations of some markers with other clinicopathological features (stage and/or grade), and wide methodological variability in markers' assessment. All these factors represent principal influences followed by intratumoral heterogeneity and geographic variation in the frequency of detection of particular markers, whereas the role of other potential influences (e.g., pre-adjuvant treatment, interaction between markers) remains rather unclear. Better understanding and elucidation of the various influences may provide a more accurate picture of the segmental distribution of molecular markers in CRC, potentially allowing the application of a novel patient stratification for treatment, based on particular molecular profiles in combination with tumor location. PMID- 26842925 TI - A possible role of GDDR in the development of Helicobacter pylori-associated gastric cancer. AB - Helicobacter pylori (H. pylori) infection plays an important part in the development of gastric carcinoma. GDDR has been confirmed as a tumor suppressor gene in gastric tumorigenesis. However, the underlying mechanism of GDDR in H. pylori-induced carcinogenesis is not well known. The aim of this study is to investigate the clinicopathological significance and possible molecular mechanism of GDDR in gastric cancer associated with H. pylori. Western blot, real-time quantitative PCR (qRT-PCR), and immunohistochemistry were used to detect the expression level of GDDR with or without H. pylori infection. The function and possible related molecular mechanisms of GDDR were further explored in vitro and in vivo. The variability of GDDR expression appeared in the early stage of gastric carcinogenesis with positive H. pylori infection status. GDDR might inhibit the progression of normal gastric epithelial cells to cancer cells by suppressing NF-kappaB signaling pathway, which in turn could be regulated by H. pylori infection. Our results suggested, for the first time, that the gradual change in GDDR expression might not only be directly related to H. pylori infection but also be an early molecular event in the development of gastric carcinoma. PMID- 26842927 TI - DNA vaccination with a gene encoding Toxoplasma gondii Rhoptry Protein 17 induces partial protective immunity against lethal challenge in mice. AB - Toxoplasma gondii is an obligate intracellular apicomplexan parasite that affects humans and various vertebrate livestock and causes serious economic losses. To develop an effective vaccine against T. gondii infection, we constructed a DNA vaccine encoding the T. gondii rhoptry protein 17 (TgROP17) and evaluated its immune protective efficacy against acute T. gondii infection in mice. The DNA vaccine (p3*Flag-CMV-14-ROP17) was intramuscularly injected to BALB/c mice and the immune responses of the vaccinated mice were determined. Compared to control mice treated with empty vector or PBS, mice immunized with the ROP17 vaccine showed a relatively high level of specific anti-T. gondii antibodies, and a mixed IgG1/IgG2a response with predominance of IgG2a production. The immunized mice also displayed a specific lymphocyte proliferative response, a Th1-type cellular immune response with production of IFN-gamma and interleukin-2, and increased number of CD8(+) T cells. Immunization with the ROP17 DNA significantly prolonged the survival time (15.6 +/- 5.4 days, P < 0.05) of mice after challenge infection with the virulent T. gondii RH strain (Type I), compared with the control groups which died within 8 days. Therefore, our data suggest that DNA vaccination with TgROP17 triggers significant humoral and cellular responses and induces effective protection in mice against acute T. gondii infection, indicating that TgROP17 is a promising vaccine candidate against acute toxoplasmosis. PMID- 26842926 TI - Immunization of stromal cell targeting fibroblast activation protein providing immunotherapy to breast cancer mouse model. AB - Unlike heterogeneous tumor cells, cancer-associated fibroblasts (CAF) are genetically more stable which serve as a reliable target for tumor immunotherapy. Fibroblast activation protein (FAP) which is restrictively expressed in tumor cells and CAF in vivo and plays a prominent role in tumor initiation, progression, and metastasis can function as a tumor rejection antigen. In the current study, we have constructed artificial FAP(+) stromal cells which mimicked the FAP(+) CAF in vivo. We immunized a breast cancer mouse model with FAP(+) stromal cells to perform immunotherapy against FAP(+) cells in the tumor microenvironment. By forced expression of FAP, we have obtained FAP(+) stromal cells whose phenotype was CD11b(+)/CD34(+)/Sca-1(+)/FSP-1(+)/MHC class I(+). Interestingly, proliferation capacity of the fibroblasts was significantly enhanced by FAP. In the breast cancer-bearing mouse model, vaccination with FAP(+) stromal cells has significantly inhibited the growth of allograft tumor and reduced lung metastasis indeed. Depletion of T cell assays has suggested that both CD4(+) and CD8(+) T cells were involved in the tumor cytotoxic immune response. Furthermore, tumor tissue from FAP-immunized mice revealed that targeting FAP(+) CAF has induced apoptosis and decreased collagen type I and CD31 expression in the tumor microenvironment. These results implicated that immunization with FAP(+) stromal cells led to the disruption of the tumor microenvironment. Our study may provide a novel strategy for immunotherapy of a broad range of cancer. PMID- 26842928 TI - Effects of solar radiation on endurance exercise capacity in a hot environment. AB - PURPOSE: The present study investigated the effects of variations in solar radiation on endurance exercise capacity and thermoregulatory responses in a hot environment. METHODS: Eight male volunteers performed four cycle exercise trials at 70 % maximum oxygen uptake until exhaustion in an environmental chamber maintained at 30 degrees C and 50 % relative humidity. Volunteers were tested under four solar radiation conditions: 800, 500, 250 and 0 W/m(2). RESULTS: Exercise time to exhaustion was less on the 800 W/m(2) trial (23 +/- 4 min) than on all the other trials (500 W/m(2) 30 +/- 7 min; P < 0.05, 250 W/m(2) 43 +/- 10 min; P < 0.001, 0 W/m(2) 46 +/- 10 min; P < 0.001), and on the 500 W/m(2) trial than the 250 W/m(2) (P < 0.05) and 0 W/m(2) (P < 0.01) trials. There were no differences in core (rectal) temperature, total sweat loss, heart rate, skin blood flow, cutaneous vascular conductance and percentage changes in plasma volume between trials (P > 0.05). Mean skin temperature was higher on the 800 W/m(2) trial than the 250 and 0 W/m(2) trials (P < 0.05), and on the 500 W/m(2) trial than the 0 W/m(2) trial (P < 0.05). The core-to-skin temperature gradient was narrower on the 800 W/m(2) trial than the 250 and 0 W/m(2) trials (P < 0.05). CONCLUSION: The present study demonstrates that endurance exercise capacity in a hot environment falls progressively as solar radiation increases. PMID- 26842929 TI - Care delivery and self management strategies for adults with epilepsy. AB - BACKGROUND: Researchers have criticised epilepsy care for adults for its lack of impact, stimulating the development of various service models and strategies to respond to perceived inadequacies. OBJECTIVES: To assess the effects of any specialised or dedicated intervention beyond that of usual care in adults with epilepsy. SEARCH METHODS: For the latest update of this review, we searched the Cochrane Epilepsy Group Specialized Register (9 December 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 11), MEDLINE (1946 to June 2013), EMBASE (1988 to June 2013), PsycINFO (1887 to December 2013) and CINAHL (1937 to December 2013). In addition, we contacted experts in the field to seek information on unpublished and ongoing studies, checked the websites of epilepsy organisations and checked the reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials, controlled or matched trials, cohort studies or other prospective studies with a control group, and time series studies. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted all data, and assessed the quality of all included studies. MAIN RESULTS: Our review included 18 different studies of 16 separate interventions, which we classified into seven distinct groups. Most of the studies have methodological weaknesses, and many results from other analyses within studies need to be interpreted with caution because of study limitations. Consequently, there is currently limited evidence for the effectiveness of interventions to improve the health and quality of life in people with epilepsy. It was not possible to combine study results in a meta analysis because of the heterogeneity of outcomes, study populations, interventions and time scales across the studies. AUTHORS' CONCLUSIONS: Two intervention types, the specialist epilepsy nurse and self management education, have some evidence of benefit. However, we did not find clear evidence that other service models substantially improve outcomes for adults with epilepsy. It is also possible that benefits are situation specific and may not apply to other settings. These studies included only a small number of service providers whose individual competence or expertise may have had a significant impact on outcomes. At present it is not possible to advocate any single model of service provision. PMID- 26842930 TI - Mitochondrial Ca(2+) Processing by a Unit of Mitochondrial Ca(2+) Uniporter and Na(+)/Ca(2+) Exchanger Supports the Neuronal Ca(2+) Influx via Activated Glutamate Receptors. AB - The current study demonstrates that in hippocampal neurons mitochondrial Ca(2+) processing supports Ca(2+) influx via ionotropic glutamate (Glu) receptors. We define mitochondrial Ca(2+) processing as Ca(2+) uptake via mitochondrial Ca(2+) uniporter (MCU) combined with subsequent Ca(2+) release via mitochondrial Na(+)/Ca(2+) exchanger (NCX). Our tool is to measure the Ca(2+) influx rate in primary hippocampal co-cultures, i.e. neurons and astrocytes, by fluorescent digital microscopy, using a Fura-2-quenching method where we add small amounts of Mn(2+) in the superfusion medium. Thus, Ca(2+) influx is measured with Mn(2+) in the bath. Ru360 as inhibitor of mitochondrial Ca(2+) uptake through MCU strongly reduces the rate of Ca(2+) influx in Glu-stimulated primary hippocampal neurons. Similarly, the Ca(2+) influx rate in Glu-stimulated neurons declines after suppression of potential-dependent MCU, when we depolarize mitochondria with rotenone. With inhibition of Ca(2+) release from mitochondria via NCX using CGP 37157 the Ca(2+) influx via N-methyl-D-aspartate (NMDA)- and kainate-sensitive receptors is slowed down. Working jointly as mitochondrial Ca(2+) processing unit, MCU and NCX, apparently sustain the Ca(2+) throughput of activated Glu sensitive receptors. Our results revise the role frequently attributed to mitochondria in neuronal Ca(2+) homeostasis, where mitochondria function mainly as Ca(2+) buffer, and prevent excessively high cytosolic Ca(2+) concentration increase during neuronal activity. The mechanism to control Ca(2+) influx in neurons, as discovered in this study, highlights mitochondrial Ca(2+) processing as a promising pharmacological target. We discuss this pathway in relation to the endoplasmic reticulum-related mechanisms of Ca(2+) processing. PMID- 26842932 TI - Just a Collection of Recollections: Clinical Ethics Consultation and the Interplay of Evaluating Voices. AB - Despite increased attention to the question of how best to evaluate clinical ethics consultations and emphasis on external evaluation (Hastings Center Report, ASBH Quality Attestation Process), there has been little sustained focus on how we, as clinicians, make sense of and learn from our own experiences in the midst of any one consultation. Questions of how we evaluate the request for, unfolding of, and conclusion of any specific ethics consultation are often overlooked, along with the underlying question of whether it is possible to give an accurate account of clinical ethics consultants' experience as experienced by ethics consultants. Before the challenge of submitting one's accounts or case reports for review and evaluation from others (at one's local institution or in the broader field), there is an underlying challenge of understanding and evaluating our own accounts. To highlight this crucial and deeply challenging dimension of actual clinical ethics practice, we present an account of a complex consultation, explicitly constructed to engage the reader in the unfolding experience of the consultant by emphasizing the multiple perspectives unfolding within the consultant's experience. Written in script format, the three perspectives presented-prototypical clinically descriptive account; didactically reflective and self-evidentiary account often seen in journal presentations; highly self critical reflective account emphasizing uncertainties inherent to clinical ethics practice-reflect different manners for responding to the ways actual clinical involvement in ethics consultation practice accentuates and refocuses the question of how to understand and evaluate our own work, as well as that of our colleagues. PMID- 26842933 TI - Extra hour of sitting each day is linked to 22% higher odds of type 2 diabetes. PMID- 26842931 TI - Lipopolysaccharide Upregulates the Expression of CINC-3 and LIX in Primary NG2 Cells. AB - Numerous NG2 cells, also called oligodendrocyte progenitor cells (OPCs), exist ubiquitously in the gray and white matter in the adult central nervous system (CNS). Although NG2 cells could become active by upregulation of NG2 expression and hypertrophy or extension of their processes under various neuropathological conditions, their actual role in the brain remains to be illustrated. In view of the fact that the synergy of cytokine and chemokine networks plays an important role in CNS inflammation and immunity, we have assumed that the NG2 cells might take part in brain inflammation and immunity by making a contribution to the pool of cytokines or chemokines. In the current study, NG2-expressing OPCs were prepared from cerebral hemispheres of postnatal day 0 or 1 Sprague-Dawley rats. Our results showed that NG2-expressing OPCs, verified by immunohistological staining of anti-NG2 antibody and anti-platelet-derived growth factor receptor alpha (PDGFRalpha) antibody, presented binding affinity to lipopolysaccharide (LPS), a commonly used stimulator in a neuroinflammatory model. Using cytokine antibody array, QPCR and ELISA, we have further shown that LPS could upregulate the expression of cytokine induced neutrophil chemoattractant-3 (CINC-3) and LPS induced CXC chemokine (LIX) in primary NG2-expressing OPCs, without the alteration in cell number of NG2-expressing OPCs. In addition, the cells bearing the receptor for these two cytokines included microglia and OPCs. Taken together, our results suggest that NG2-expressing OPCs could response to LPS and may take part in neuroinflammatory process, through secreting cytokines and chemokines to exert an effect on target cells (OPCs and microglia). PMID- 26842934 TI - A multi-zoned white organic light-emitting diode with high CRI and low color temperature. AB - White organic light emitting diodes (WOLEDs) is becoming a new platform technology for a range of applications such as flat-panel displays, solid-state lightings etc., and are under intensive research. For general solid-state illumination applications, a WOLED's color rendering index (CRI) and correlated color temperature (CCT) are two crucial parameters. This paper reports that WOLED device structures can be constructed using four stacked emission layers which independently emit lights at blue, green, yellow and red color respectively. The intensity of each emission layer is then engineered by funneling excitons to the targeted emission layer to achieve an ultrahigh 92 CRI at 5000 cd/m(2), and to reduce CCT to below 2500 K. PMID- 26842936 TI - Structural Basis of Cargo Recognition by Unconventional Myosins in Cellular Trafficking. AB - Unconventional myosins are a superfamily of actin-based molecular motors playing diverse roles including cellular trafficking, mechanical supports, force sensing and transmission, etc. The variable neck and tail domains of unconventional myosins function to bind to specific cargoes including proteins and lipid vesicles and thus are largely responsible for the diverse cellular functions of myosins in vivo. In addition, the tail regions, together with their cognate cargoes, can regulate activities of the motor heads. This review outlines the advances made in recent years on cargo recognition and cargo binding-induced regulation of the activity of several unconventional myosins including myosin-I, V, VI and X in cellular trafficking. We approach this topic by describing a series of high-resolution structures of the neck and tail domains of these unconventional myosins either alone or in complex with their specific cargoes, and by discussing potential implications of these structural studies on cellular trafficking of these myosin motors. PMID- 26842937 TI - ETHICS OF NEW TECHNOLOGIES. Finding an ethical path forward for mitochondrial replacement. PMID- 26842938 TI - C2H2 adsorption in three isostructural metal-organic frameworks: boosting C2H2 uptake by rational arrangement of nitrogen sites. AB - Replacing the benzene spacer in the organic linker 5,5'-(benzene-1,4 diyl)diisophthalate with the nitrogen containing heterocyclic rings, namely, pyrazine, pyridazine, and pyrimidine results in three organic linkers, which were reacted with copper ions under solvothermal conditions to form three isostructural metal-organic frameworks (ZJNU-46, ZJNU-47 and ZJNU-48) exhibiting exceptionally high sorption capacities with regard to acetylene due to the simultaneous immobilization of open metal sites and Lewis basic nitrogen sites in the frameworks. At 1 atm and 295 K, the gravimetric C2H2 adsorption uptakes reach 187, 213 and 193 cm(3) (STP) g(-1) for these three compounds. The gravimetric C2H2 adsorption amount of ZJNU-47a is the second highest reported for MOF materials. Notably, despite their same porosities, and densities of open metal sites and uncoordinated nitrogen sites, distinctly different C2H2 adsorption capacities were observed for these three compounds, which we think are mainly associated with the difference in the relative position of nitrogen atoms leading to different binding affinities of the frameworks towards C2H2 guest molecules, and thus different C2H2 adsorptions. This work demonstrates that the rational arrangement of open nitrogen sites will favorably improve the C2H2 uptake and thus provides useful information for future design of porous MOFs with high acetylene storage capacities. PMID- 26842935 TI - Aurora kinase targeting in lung cancer reduces KRAS-induced transformation. AB - BACKGROUND: Activating mutations in KRAS are prevalent in lung cancer and have been causally linked to the oncogenic process. However, therapies targeted to oncogenic RAS have been ineffective to date and identification of KRAS targets that impinge on the oncogenic phenotype is warranted. Based on published studies showing that mitotic kinases Aurora A (AURKA) and B (AURKB) cooperate with oncogenic RAS to promote malignant transformation and that AURKA phosphorylates RAS effector pathway components, the aim of this study was to investigate whether AURKA and AURKB are KRAS targets in lung cancer and whether targeting these kinases might be therapeutically beneficial. METHODS: In order to determine whether oncogenic KRAS induces Aurora kinase expression, we used qPCR and western blotting in three different lung cell-based models of gain- or loss-of-function of KRAS. In order to determine the functional role of these kinases in KRAS induced transformation, we generated KRAS-positive A549 and H358 cells with stable and inducible shRNA-mediated knockdown of AURKA or AURKB and evaluated transformation in vitro and tumor growth in vivo. In order to validate AURKA and/or AURKB as therapeutically relevant KRAS targets in lung cancer, we treated A549 and H358 cells, as well as two different lung cell based models of gain-of function of KRAS with a dual Aurora kinase inhibitor and performed functional in vitro assays. RESULTS: We determined that KRAS positively regulates AURKA and AURKB expression. Furthermore, in KRAS-positive H358 and A549 cell lines, inducible knockdown of AURKA or AURKB, as well as treatment with a dual AURKA/AURKB inhibitor, decreased growth, viability, proliferation, transformation, and induced apoptosis in vitro. In addition, inducible shRNA mediated knockdown of AURKA in A549 cells decreased tumor growth in vivo. More importantly, dual pharmacological inhibiton of AURKA and AURKB reduced growth, viability, transformation, and induced apoptosis in vitro in an oncogenic KRAS dependent manner, indicating that Aurora kinase inhibition therapy can specifically target KRAS-transformed cells. CONCLUSIONS: Our results support our hypothesis that Aurora kinases are important KRAS targets in lung cancer and suggest Aurora kinase inhibition as a novel approach for KRAS-induced lung cancer therapy. PMID- 26842939 TI - Structured triglycerides versus physical mixtures of medium- and long-chain triglycerides for parenteral nutrition in surgical or critically ill adult patients: Systematic review and meta-analysis. AB - INTRODUCTION: New generations of parenteral lipid emulsions combine Long Chain Triglycerides (LCTs) with Medium Chain Triglycerides (MCTs) either by physically mixing MCT- and LCT-containing oils or by using synthetically structured triglycerides (STGs). In order to clarify some open issues relating to their comparative effect, in particular in terms of clinical outcomes, pertinent evidence was systematically identified, reviewed and meta-analyzed. METHODS: PubMed, Scopus, Wanfang Data, China Hospital Knowledge Database and Google Scholar were searched for published clinical trials comparing STGs vs. MCTs/LCTs PN regimens administered over 5-7 days in surgical and/or critically ill patients. Two independent investigators performed screening and data extraction using a predefined list of parameters. Data were pooled using RevMan(r) 5.2. Quality of evidence was assessed according to Cochrane's risk of bias tool. Pre specified high quality (HQ), incremental analyses and a post hoc subgroup analysis were performed. RESULTS: 21 studies were included. The meta-analysis revealed a significantly better cumulative nitrogen balance (Std. mean difference [95% CI]) (1.34 [0.98-1.7], p < 0.00001), as well as higher values for pre albumin (24.99 mg/L [6.71-43.27], p < 0.000001), and albumin (1.22 g/L [0.66 1.77] p < 0.0001), while plasma triglycerides were significantly lower (-0.28 mmol/L [-0.41 to -0.15], p < 0.0001) in the STG vs. MCT/LCT group. ALT, AST, and GGT were significantly lower with STGs than with MCTs/LCTs, while for total bilirubin and ALP only a trend was observed. STGs were also associated with a trend to a shorter hospital length of stay (LOS) (-1.74 days [-3.49 to 0.01] p = 0.05). Quality of evidence was affected by an unclear risk of selection bias, mostly due to the lack of detailed reporting (random sequence generation, allocation concealment). For the other domains, most of the weighted information was judged at low risk of bias. HQ estimated effects, incremental and subgroup analyses were consistent with the main analysis. CONCLUSIONS: In postsurgical and/or critically ill patients, the administration of STGs vs. MCT/LCTs was significantly associated with improved protein economy, better liver tolerance and a more efficient triglyceride elimination. With regard to clinical outcomes a strong trend towards reduced LOS was observed for STG patients. PMID- 26842940 TI - A characterization of grapevine of GRAS domain transcription factor gene family. AB - GRAS domain genes are a group of important plant-specific transcription factors that have been reported to be involved in plant development. In order to know the roles of GRAS genes in grapevine, a widely cultivated fruit crop, the study on grapevine GRAS (VvGRAS) was carried out, and from which, 43 were identified from 12* assemble grapevine genomic sequences. Further, the genomic structures, synteny, phylogeny, expression profiles in different tissues of these genes, and their roles in response to stress were investigated. Among the genes, two potential target genes (VvSCL15 and VvSCL22) for VvmiR171 were experimentally verified by PPM-RACE and RLM-RACE, in that not only the cleavage sites of miR171 on the target mRNA were mapped but also the cleaved fragments and their expressing patterns were detected. Transgenic Arabidopsis plants over expression VvSCL15 showed lower tolerance to drought and salt treatments. PMID- 26842942 TI - Change in haematological and selected biochemical parameters measured in feline blood donors and feline whole blood donated units. AB - Objectives The quality of whole blood (WB) units is influenced by many factors, starting with selection of donors and the method of blood collection. The aim of this study was to investigate the changes that occur in haematological and selected biochemical parameters in blood transferred from a feline blood donor to feline WB unit. Methods Data from 27 feline blood donations were used in this study. Cats were anaesthetised with a combination of tiletamine and zolazepam. Blood (10 ml/kg body weight to a maximum of 60 ml/cat) was collected in citrate phosphate-dextrose-adenine (CPDA) anticoagulant. Lactated Ringer's solution (10 ml/kg) was administered intravenously starting halfway through the donation. Haematological and selected biochemical parameters (complete blood count, free haemoglobin, % haemolysis, glucose, sodium, potassium, pH) were measured in the blood donor before donation and in the corresponding donated WB unit soon after collection. Results Significant decreases occurred between blood donor and WB unit in red blood cells (mean difference -1.06 * 1012/l; P <0.0001), haemoglobin (mean difference -1.6 g/dl; P <0.0001), haematocrit (mean difference -4.6%; P <0.0001), red cell distribution width (mean difference -0.9%; P = 0.0003), white blood cells (mean difference -2.17 * 109/l; P <0.0001), pH (mean difference -0.5; P <0.0001) and potassium (mean difference -1.4 mmol/l; P <0.0001). Significant increases occurred between blood donor and WB unit in platelets (mean difference +87.00 *109/l; P = 0.0039), glucose (mean difference +25.42 mmol/l; P <0.0001) and sodium (mean difference +20 mmol/l; P <0.0001). Conclusions and relevance When using a blood collection protocol with intravenous fluid administration midway through the donation and a CPDA:blood ratio of 1:7, there were significant changes in both the haematological and biochemical characteristics between the blood donors and WB units. The majority of these changes may be the result of the anticoagulants used for storage. Understanding these changes may assist selection of blood donors and help prediction of the characteristics of the donated WB unit. PMID- 26842943 TI - Tympanic ear thermometer assessment of body temperature among patients with cognitive disturbances. An acceptable and ethically desirable alternative? AB - AIM: Investigation of a possible relation between body temperature measurements by the current generation of tympanic ear and rectal thermometers. BACKGROUND: In Denmark, a national guideline recommends the rectal measurement. Subsequently, the rectal thermometers and tympanic ear devices are the most frequently used and first choice in Danish hospital wards. Cognitive changes constitute challenges with cooperating in rectal temperature assessments. With regard to diagnosing, ethics, safety and the patients' dignity, the tympanic ear thermometer might comprise a desirable alternative to rectal noninvasive measurement of body temperature during in-hospital-based neurorehabilitation. DESIGN: A prospective, descriptive cohort study. Consecutive inclusion of 27 patients. Linear regression models were used to analyse 284 simultaneous temperature measurements. ETHICS: Ethical approval for this study was granted by the Danish Data Protection Agency, and the study was completed in accordance with the Helsinki Declaration 2008. RESULTS: About 284 simultaneous rectal and ear temperature measurements on 27 patients were analysed. The patient-wise variability of measured temperatures was significantly higher for the ear measurements. Patient-wise linear regressions for the 25 patients with at least three pairs of simultaneous ear and rectal temperature measurements showed large interpatient variability of the association. CONCLUSION: A linear relationship between the rectal body temperature assessment and the temperature assessment employing the tympanic thermometer is weak. Both measuring methods reflect variance in temperature, but ear measurements showed larger variation. PMID- 26842941 TI - The Cannabinoid CB1/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation In Vitro and Neuroprotection During the Cuprizone-Induced Central Nervous System Demyelination. AB - AIM AND METHODS: Different types of insults to the CNS lead to axon demyelination. Remyelination occurs when the CNS attempts to recover from myelin loss and requires the activation of oligodendrocyte precursor cells. With the rationale that CB1 receptor is expressed in oligodendrocytes and marijuana consumption alters CNS myelination, we study the effects of the cannabinoid agonist WIN55212.2 in (1) an in vitro model of oligodendrocyte differentiation and (2) the cuprizone model for demyelination. RESULTS: The synthetic cannabinoid agonist WIN55212.2 at 1 MUM increased the myelin basic protein mRNA and protein expression in vitro. During cuprizone-induced acute demyelination, the administration of 0.5 mg/kg WIN55212.2 confers more myelinated axons, increased the expression of retinoid X receptor alpha, and declined nogo receptor expression. Controversially, 1 mg/kg of the drug increased the number of demyelinated axons and reduced the expression of nerve growth factor inducible, calreticulin and myelin-related genes coupling specifically with a decrease in 2',3'-cyclic nucleotide 3' phosphodiesterase expression. CONCLUSION: The cannabinoid agonist WIN55212.2 promotes oligodendrocyte differentiation in vitro. Moreover, 0.5 mg/kg of the drug confers neuroprotection during cuprizone-induced demyelination, while 1 mg/kg aggravates the demyelination process. PMID- 26842944 TI - In Situ Solid-State (13)C NMR Observation of Pore Mouth Catalysis in Etherification of beta-Citronellene with Ethanol on Zeolite Beta. AB - The reaction mechanism of etherification of beta-citronellene with ethanol in liquid phase over acid zeolite beta is revealed by in situ solid-state (13)C NMR spectroscopy. Comparison of (13)C Hahn-echo and (1)H-(13)C cross-polarization NMR characteristics is used to discriminate between molecules freely moving in liquid phase outside the zeolite and molecules adsorbed inside zeolite pores and in pore mouths. In the absence of ethanol, beta-citronellene molecules enter zeolite pores and react to isomers. In the presence of ethanol, the concentration of beta citronellene inside zeolite pores is very low because of preferential adsorption of ethanol. The etherification reaction proceeds by adsorption of beta citronellene molecule from the external liquid phase in a pore opening where it reacts with ethanol from inside the pore. By competitive adsorption, ethanol prevents the undesired side reaction of beta-citronellene isomerization inside zeolite pores. beta-citronellene etherification on zeolite beta is suppressed by bulky base molecules (2,4,6-collidine and 2,6-ditertiarybutylpyridine) that do not enter the zeolite pores confirming the involvement of easily accessible acid sites in pore openings. The use of in situ solid-state NMR to probe the transition from intracrystalline catalysis to pore mouth catalysis depending on reaction conditions is demonstrated for the first time. The study further highlights the potential of this NMR approach for investigations of adsorption of multicomponent mixtures in general. PMID- 26842945 TI - Tanning as a substance abuse. AB - While few people would deny the appeal of a day in the sun there are some who seem to take it too far. In recent years the concept of 'tanning addiction' has become popular and several studies have supported the notion of viewing exposure to UV radiation as a form of substance abuse. In this article we will review some of the literature on sun seeking behavior. PMID- 26842946 TI - Erratum to: South African Herbal Extracts as Potential Chemopreventive Agents: Screening for Anticancer Splicing Activity. PMID- 26842948 TI - A compact and integrated immunoassay with on-chip dispensing and magnetic particle handling. AB - We present a compact diagnostic platform for a rapid and sensitive detection of plasma biomarkers. The platform consists of a disposable microfluidic polymer chip, a processing device including a lens-free and cost efficient sensor system and a setup for dispersion of magnetic particles. The biomarkers of interest are quantified by magnetic bead based immunoassays with chemiluminescent readout technology. With a novel system for dispersion and manipulation of the magnetic particles in combination with chemiluminescence detection, the sensitivity of the immunoassay is improved and enables a rapid assay in a microfluidic format. In the disposable chip, extra chambers for storage and dispensing of biomarker specific reagents are integrated, which reduce the need of external dosing devices and thereby the cost of the platform is decreased. Plasma biomarkers for monitoring of sepsis could be quantified at 10 pg/mL concentrations within a total time of 30 min by the present system. This contribution is a fundamental step towards the development of an automatic and compact Point-of-Care testing device for monitoring of patients at the intensive care unit. PMID- 26842947 TI - Analysis of genetic admixture in Uyghur using the 26 Y-STR loci system. AB - The Uyghur population has experienced extensive interaction with European and Eastern Asian populations historically. A set of high-resolution genetic markers could be useful to infer the genetic relationships between the Uyghur population and European and Asian populations. In this study we typed 100 unrelated Uyghur males living in southern Xinjiang at 26 Y-STR loci. Using the high-resolution 26 Y-STR loci system, we investigated genetic and phylogenetic relationship between the Uyghur population and 23 reference European or Asian populations. We found that the Uyghur population exhibited a genetic admixture of Eastern Asian and European populations, and had a slightly closer relationship with the selected European populations than the Eastern Asian populations. We also demonstrated that the 26 Y-STR loci system was potentially useful in forensic sciences because it has a large power of discrimination and rarely exhibits common haplotypes. However, ancestry inference of Uyghur samples could be challenging due to the admixed nature of the population. PMID- 26842949 TI - Fabrication and characterization of gels with integrated channels using 3D printing with microfluidic nozzle for tissue engineering applications. AB - The lack of a simple and effective method to integrate vascular network with engineered scaffolds and tissue constructs remains one of the biggest challenges in true 3D tissue engineering. Here, we detail the use of a commercially available, low-cost, open-source 3D printer modified with a microfluidic print head in order to develop a method for the generation of instantly perfusable vascular network integrated with gel scaffolds seeded with cells. The print-head features an integrated coaxial nozzle that allows the fabrication of hollow, calcium-polymerized alginate tubes that can be easily patterned using 3D printing techniques. The diameter of the hollow channel can be precisely controlled and varied between 500 MUm - 2 mm by changing applied flow rates or print-head speed. These channels are integrated into gel layers with a thickness of 800 MUm - 2.5 mm. The structural rigidity of these constructs allows the fabrication of multi layered structures without causing the collapse of hollow channels in lower layers. The 3D printing method was fully characterized at a range of operating speeds (0-40 m/min) and corresponding flow rates (1-30 mL/min) were identified to produce precise definition. This microfluidic design also allows the incorporation of a wide range of scaffold materials as well as biological constituents such as cells, growth factors, and ECM material. Media perfusion of the channels causes a significant viability increase in the bulk of cell-laden structures over the long-term. With this setup, gel constructs with embedded arrays of hollow channels can be created and used as a potential substitute for blood vessel networks. PMID- 26842954 TI - Error in Author Affiliations. Use of lithium and anticonvulsants and the rate of chronic kidney disease: a nationwide population-based study. PMID- 26842950 TI - A randomised trial evaluating anakinra in early active rheumatoid arthritis. AB - OBJECTIVES: The effectiveness of anakinra (interleukin-1 receptor antagonist) in early rheumatoid arthritis (RA) is unknown. We evaluated the efficacy of anakinra (combined with methotrexate) in a randomised clinical trial of early active RA patients. METHODS: The Combination Anti-Rheumatic Drugs in Early RA-2 (CARDERA-2) trial was a randomised trial of early (duration <1 year) active RA. Patients were randomised to 12 months of: (1) methotrexate or (2) anakinra-methotrexate. Follow up lasted 2 years. The primary outcome was erosive progression (changes from baseline in modified Larsen scores). Secondary outcomes were changes from baseline in disease activity score on a 28-joint count (DAS28), health assessment questionnaire (HAQ), and quality of life (EQ-5D) scores alongside ACR responder rates. RESULTS: 154 patients received the allocated intervention (from 259 screened). Similar Larsen score progression was seen at 12 and 24 months in patients receiving anakinra-methotrexate (mean changes from baseline of 2.50 and 5.10, respectively) and methotrexate monotherapy (mean changes from baseline of 4.16 and 5.20, respectively). Lower improvements in DAS28 and HAQ scores were seen at all time-points in anakinra-methotrexate treated patients; these were significantly less at 24 months (DAS28 p=0.04; HAQ P=0.02). Significantly lower EQ-5D score increases were seen at 12 months with anakinra-methotrexate (p=0.03). Anakinra-methotrexate was associated with more serious adverse events compared with methotrexate monotherapy (11 vs. 6 patients), although this was not significant (p=0.59). CONCLUSIONS: Anakinra (combined with methotrexate) is not effective in early, active RA. It provided no clinical benefits beyond methotrexate monotherapy. PMID- 26842951 TI - The genome of newly classified Ochroconis mirabilis: Insights into fungal adaptation to different living conditions. AB - BACKGROUND: Ochroconis mirabilis, a recently introduced water-borne dematiaceous fungus, is occasionally isolated from human skin lesions and nails. We identified an isolate of O. mirabilis from a skin scraping with morphological and molecular studies. Its genome was then sequenced and analysed for genetic features related to classification and biological characteristics. RESULTS: UM 578 was identified as O. mirabilis based on morphology and internal transcribed spacer (ITS)-based phylogeny. The 34.61 Mb assembled genome with 13,435 predicted genes showed less efficiency of this isolate in plant cell wall degradation. Results from the peptidase comparison analysis with reported keratin-degrading peptidases from dermatophytes suggest that UM 578 is very unlikely to be utilising these peptidases to survive in the host. Nevertheless, we have identified peptidases from M10A, M12A and S33 families that may allow UM 578 to invade its host via extracellular matrix and collagen degradation. Furthermore, the lipases in UM 578 may have a role in supporting the fungus in host invasion. This fungus has the potential ability to synthesise melanin via the 1,8-dihydroxynaphthalene (DHN) melanin pathway and to produce mycotoxins. The mating ability of this fungus was also inspected in this study and a mating type gene containing alpha domain was identified. This fungus is likely to produce taurine that is required in osmoregulation. The expanded gene family encoding the taurine catabolism dioxygenase TauD/TdfA domain suggests the utilisation of taurine under sulfate starvation. The expanded glutathione-S-transferase domains and RTA1-like protein families indicate the selection of genes in UM 578 towards adaptation in hostile environments. CONCLUSIONS: The genomic analysis of O. mirabilis UM 578 provides a better understanding of fungal survival tactics in different habitats. PMID- 26842956 TI - Erythematous Papules and Plaques on the Cheeks. PMID- 26842955 TI - MeCP2 SUMOylation rescues Mecp2-mutant-induced behavioural deficits in a mouse model of Rett syndrome. AB - The methyl-CpG-binding protein 2 (MeCP2) gene, MECP2, is an X-linked gene encoding the MeCP2 protein, and mutations of MECP2 cause Rett syndrome (RTT). However, the molecular mechanism of MECP2-mutation-caused RTT is less known. Here we find that MeCP2 could be SUMO-modified by the E3 ligase PIAS1 at Lys-412. MeCP2 phosphorylation (at Ser-421 and Thr-308) facilitates MeCP2 SUMOylation, and MeCP2 SUMOylation is induced by NMDA, IGF-1 and CRF in the rat brain. MeCP2 SUMOylation releases CREB from the repressor complex and enhances Bdnf mRNA expression. Several MECP2 mutations identified in RTT patients show decreased MeCP2 SUMOylation. Re-expression of wild-type MeCP2 or SUMO-modified MeCP2 in Mecp2-null neurons rescues the deficits of social interaction, fear memory and LTP observed in Mecp2 conditional knockout (cKO) mice. These results together reveal an important role of MeCP2 SUMOylation in social interaction, memory and synaptic plasticity, and that abnormal MeCP2 SUMOylation is implicated in RTT. PMID- 26842957 TI - Monotherapy with Levetiracetam Versus Older AEDs: A Randomized Comparative Trial of Effects on Bone Health. AB - Long-term anti-epileptic drug (AED) therapy is associated with increased fracture risk. This study tested whether substituting the newer AED levetiracetam has less adverse effects on bone than older AEDs. An open-label randomized comparative trial. Participants had "failed" initial monotherapy for partial epilepsy and were randomized to substitution monotherapy with levetiracetam or an older AED (carbamazepine or valproate sodium). Bone health assessments, performed at 3 and 15 months, included areal bone mineral density (aBMD) and content at lumbar spine (LS), total hip (TH), forearm (FA), and femoral neck (FN), radial and tibial peripheral quantitative computed tomography and serum bone turnover markers. Main outcomes were changes by treatment group in aBMD at LS, TH, and FA, radial and tibial trabecular BMD and cortical thickness. 70/84 patients completed assessments (40 in levetiracetam- and 30 in older AED group). Within-group analyses showed decreases in both groups in LS (-9.0 %; p < 0.001 in levetiracetam vs. -9.8 %; p < 0.001 in older AED group), FA (-1.46 %; p < 0.001 vs. -0.96 %; p < 0.001, respectively) and radial trabecular BMD (-1.46 %; p = 0.048 and -2.31 %; p = 0.013, respectively). C-terminal telopeptides of type I collagen (betaCTX; bone resorption marker) decreased in both groups (-16.1 %; p = 0.021 vs. -15.2 %; p = 0.028, respectively) whereas procollagen Iota N-terminal peptide (PIotaNP; bone formation marker) decreased in older AED group (-27.3 %; p = 0.008). The treatment groups did not differ in any of these measures. In conclusion, use of both levetiracetam and older AEDs was associated with bone loss over 1 year at clinically relevant fracture sites and a reduction in bone turnover. PMID- 26842958 TI - The roles of arbuscular mycorrhizal fungi (AMF) in phytoremediation and tree-herb interactions in Pb contaminated soil. AB - Understanding the roles of arbuscular mycorrhizal fungi (AMF) in plant interaction is essential for optimizing plant distribution to restore degraded ecosystems. This study investigated the effects of AMF and the presence of legume or grass herbs on phytoremediation with a legume tree, Robinia pseudoacacia, in Pb polluted soil. In monoculture, mycorrhizal dependency of legumes was higher than that of grass, and AMF benefited the plant biomass of legumes but had no effect on grass. Mycorrhizal colonization of plant was enhanced by legume neighbors but inhibited by grass neighbor in co-culture system. N, P, S and Mg concentrations of mycorrhizal legumes were larger than these of non-mycorrhizal legumes. Legume herbs decreased soil pH and thereby increased the Pb concentrations of plants. The neighbor effects of legumes shifted from negative to positive with increasing Pb stress levels, whereas grass provided a negative effect on the growth of legume tree. AMF enhanced the competition but equalized growth of legume-legume under unpolluted and Pb stress conditions, respectively. In conclusion, (1) AMF mediate plant interaction through directly influencing plant biomass, and/or indirectly influencing plant photosynthesis, macronutrient acquisition, (2) legume tree inoculated with AMF and co-planted with legume herbs provides an effective way for Pb phytoremediation. PMID- 26842959 TI - A child chronic cough-specific quality of life measure: development and validation. AB - BACKGROUND: Quality of life (QoL) measures are an important patient-relevant outcome measure for clinical studies. Cough is the most common symptom that results in new medical consultations. Although adult and parent-proxy cough specific QoL instruments have been shown to be a useful cough outcome measure, no suitable cough-specific QoL measure for children with chronic cough exists. We report on the statistical properties of a chronic cough-specific QoL (CC-QoL) questionnaire for children. METHOD: 130 children (median age 10 years, IQR 8-12 years; 65 girls) participated. A preliminary 37-item version was developed from conversations with children with chronic cough (>4 weeks). Children also completed generic QoL questionnaires (Pediatric QoL Inventory 4.0 (PedsQL4.0), Spence Children's Anxiety Scale (SCAS)) and cough diary scores. RESULTS: The clinical impact method of item reduction resulted in 16 items that had excellent internal consistency (Cronbach's alpha=0.94) among these items and also within each domain. Evidence for construct and criterion validity was established with significant correlations between CC-QoL subscales with cough scores, PedsQL and SCAS scores. CC-QoL scores were sensitive to change following an intervention and significant differences were noted between those children coughing and those who had ceased coughing. Minimum important difference (MID) for overall and domain CC QoL ranged from 0.37-1.36 (distribution-based approach) to 1.11-1.58 (anchor based approach). CONCLUSIONS: Chronic cough significantly impacts the QoL of children. The CC-QoL is a reliable, valid and sensitive to change outcome measure that assesses QoL from the child's perspective. Pending data from a confirmatory cohort, a MID for the CC-QoL of 1.1 is recommended when evaluating health status change. PMID- 26842960 TI - Dysautonomia in prodromal alpha-synucleinopathy: peripheral versus central autonomic degeneration. AB - BACKGROUND AND PURPOSE: There is an urgent need for early predictive markers for the course of disease in prodromal alpha-synucleinopathies such as idiopathic rapid eye movement (REM) sleep behaviour disorder. Autonomic cardiac/vascular dysfunction is a prominent feature in advanced alpha-synucleinopathies, but its diagnostic value as an early neurodegenerative marker remains unclear. The latter may be complicated since synuclein-mediated neurodegeneration may involve central and peripheral components of the autonomic nervous system. METHODS: The diagnostic value of autonomic symptoms and central and peripheral autonomic markers of blood pressure and heart rate regulation were prospectively evaluated in 20 subjects with idiopathic REM sleep behaviour disorder and 20 age-matched healthy controls. RESULTS: Although subjects with REM sleep behaviour disorder showed no clinical autonomic symptoms, blood pressure (P <= 0.035) and heart rate response (P <= 0.065) were slightly diminished during orthostatic challenge. Autonomic dysregulation was distinctively reflected in lower resting heart rate (all components, P <= 0.05) and blood pressure variability (low frequency component, P <= 0.024) indicating peripheral cardiac/vascular denervation. In contrast, baroreflex sensitivity and central cardiac autonomic outflow (sympathovagal balance) were well preserved indicating intact central autonomic regulation. Heart rate variability [very low frequency component, receiver operating characteristic (ROC) area under the curve (AUC) 0.80, P <= 0.001] and blood pressure variability (low frequency component ROC AUC 0.73, P <= 0.01) but not baroreflex sensitivity and sympathovagal balance showed an excellent diagnostic accuracy in identifying subjects with REM sleep behaviour disorder and healthy controls. CONCLUSIONS: Cardiac/vascular dysfunction in prodromal alpha synucleinopathy arises from peripheral rather than from central autonomic degeneration. Autonomic indices encoded in heart rate and blood pressure variability are precise functional markers of early synuclein-mediated neurodegeneration. PMID- 26842961 TI - Schistosoma haematobium and soil-transmitted Helminths in Tana Delta District of Kenya: infection and morbidity patterns in primary schoolchildren from two isolated villages. AB - BACKGROUND: Schistosomes and soil-transmitted helminths (STH) (hookworm, Trichuris trichiura and Ascaris lumbricoides) are widely distributed in developing countries where they infect over 230 million and 1.5 billion people, respectively. The parasites are frequently co-endemic and many individuals are co infected with two or more of the species, but information on how the parasites interact in co-infected individuals is scarce. The present study assessed Schistosoma haematobium and STH infection and morbidity patterns among school children in a hyper-endemic focus in the Tana River delta of coastal Kenya. METHODS: Two hundred and sixty-two children aged 5-12 years from two primary schools were enrolled in the study. For each child, urine was examined for S. haematobium eggs and haematuria, stool was examined for STH eggs, peripheral blood was examined for eosinophilia and haemoglobin level, the urinary tract was ultrasound-examined for S. haematobium-related pathology, and the height and weight was measured and used to calculate the body mass index (BMI). RESULTS: Prevalences of S. haematobium, hookworm, T. trichiura and A. lumbricoides infection were 94, 81, 88 and 46 %, respectively. There was no significant association between S. haematobium and STH infection but intensity of hookworm infection significantly increased with that of T. trichiura. Lower BMI scores were associated with high intensity of S. haematobium (difference =-0.48, p > 0.05) and A. lumbricoides (difference =-0.67, p < 0.05). Haematuria (both macro and micro) was common and associated with S. haematobium infection, while anaemia was associated with high intensity of S. haematobium (OR = 2.08, p < 0.05) and high hookworm infections OR = 4.75; p < 0.001). The majority of children had eosinophilia, which was significantly associated with high intensity of hookworm infection (OR = 5.34, p < 0.05). Overall 38 % of the children had ultrasound detectable urinary tract morbidity, which was associated with high intensity of S. haematobium infection (OR = 3.13, p < 0.05). CONCLUSION: Prevalences of S. haematobium and STH infections among the primary school children were high and the parasites were responsible for significant morbidity. A clear synergistic interaction was observed between hookworm and T. trichiura infections. Increased coverage in administration of praziquantel and albendazole in the area is recommended to control morbidity due to these infections. PMID- 26842962 TI - Spin-Echo Resting-State Functional Connectivity in High-Susceptibility Regions: Accuracy, Reliability, and the Impact of Physiological Noise. AB - Gradient-echo (GE) echo-planar imaging (EPI) is the method of choice in blood oxygenation level-dependent (BOLD) functional MRI (fMRI) studies, as it demonstrates substantially higher BOLD sensitivity than its spin-echo (SE) counterpart. However, it is also well known that the GE-EPI signal is prone to signal dropouts and shifts due to susceptibility effects near air-tissue interfaces. SE-EPI, in contrast, is minimally affected by these artifacts. In this study, we quantify, for the first time, the sensitivity and specificity of SE and GE EPI for resting-state fMRI functional connectivity (fcMRI) mapping, using the 1000-brain fcMRI atlas (Yeo et al., 2011 ) as the pseudoground truth. Moreover, we assess the influence of physiological processes on resting-state BOLD measured using both regular and ultrafast GE and SE acquisitions. Our work demonstrates that SE-EPI and GE-EPI are associated with similar sensitivities, specificities, and intersubject reproducibility in fcMRI for most brain networks, generated using both seed-based analysis and independent component analysis. More importantly, SE-based fcMRI measurements demonstrated significantly higher sensitivity, specificity, and intersubject reproducibility in high-susceptibility regions, spanning the limbic and frontal networks in the 1000-brain atlas. In addition, SE-EPI is significantly less sensitive to prominent sources of physiological noise, including low-frequency respiratory volume and heart rate variations. Our work suggests that SE-EPI should be increasingly adopted in the study of networks spanning susceptibility-affected brain regions, including those that are important to memory, language, and emotion. PMID- 26842964 TI - Child mortality of children aged 5-15 years in the UK and Sweden: a comparison. PMID- 26842963 TI - ADAT3-related intellectual disability: Further delineation of the phenotype. AB - ADAT3-related intellectual disability has been recently described in 24 individuals from eight Saudi families who had cognitive impairment and strabismus. Other common features included growth failure, microcephaly, tone abnormalities, epilepsy, and nonspecific brain abnormalities. A single homozygous founder mutation (c.382G>A:p.(V128M)) in the ADAT3 gene, which encodes a protein that functions in tRNA editing, was identified in all affected individuals. In this report, we present additional 15 individuals from 11 families (10 Saudis and 1 Emirati) who are homozygous for the same founder mutation. In addition to the universal findings of intellectual disability and strabismus, the majority exhibited microcephaly and growth failure. Additional features not reported in the original cohort include dysmorphic facial features (prominent forehead, up slanted palpebral fissures, epicanthus, and depressed nasal bridge), behavioral problems (hyperactivity and aggressiveness), recurrent otitis media, and growth hormone deficiency. ADAT3-related intellectual disability is an important recognizable cause of intellectual disability in Arabia. PMID- 26842965 TI - ALS-associated mutant FUS induces selective motor neuron degeneration through toxic gain of function. AB - Mutations in FUS cause amyotrophic lateral sclerosis (ALS), including some of the most aggressive, juvenile-onset forms of the disease. FUS loss-of-function and toxic gain-of-function mechanisms have been proposed to explain how mutant FUS leads to motor neuron degeneration, but neither has been firmly established in the pathogenesis of ALS. Here we characterize a series of transgenic FUS mouse lines that manifest progressive, mutant-dependent motor neuron degeneration preceded by early, structural and functional abnormalities at the neuromuscular junction. A novel, conditional FUS knockout mutant reveals that postnatal elimination of FUS has no effect on motor neuron survival or function. Moreover, endogenous FUS does not contribute to the onset of the ALS phenotype induced by mutant FUS. These findings demonstrate that FUS-dependent motor degeneration is not due to loss of FUS function, but to the gain of toxic properties conferred by ALS mutations. PMID- 26842966 TI - Isometric hand grip strength measured by the Nintendo Wii Balance Board - a reliable new method. AB - BACKGROUND: Low hand grip strength is a strong predictor for both long-term and short-term disability and mortality. The Nintendo Wii Balance Board (WBB) is an inexpensive, portable, wide-spread instrument with the potential for multiple purposes in assessing clinically relevant measures including muscle strength. The purpose of the study was to explore intrarater reliability and concurrent validity of the WBB by comparing it to the Jamar hand dynamometer. METHOD: Intra rater test-retest cohort design with randomized validity testing on the first session. Using custom WBB software, thirty old adults (69.0 +/- 4.2 years of age) were studied for reproducibility and concurrent validity compared to the Jamar hand dynamometer. Reproducibility was tested for dominant and non-dominant hands during the same time-of-day, one week apart. Intraclass correlation coefficient (ICC) and standard error of measurement (SEM) and limits of agreement (LOA) were calculated to describe relative and absolute reproducibility respectively. To describe concurrent validity, Pearson's product-moment correlation and ICC was calculated. RESULTS: Reproducibility was high with ICC values of >0.948 across all measures. Both SEM and LOA were low (0.2-0.5 kg and 2.7-4.2 kg, respectively) in both the dominant and non-dominant hand. For validity, Pearson correlations were high (0.80-0.88) and ICC values were fair to good (0.763-0.803). CONCLUSION: Reproducibility for WBB was high for relative measures and acceptable for absolute measures. In addition, concurrent validity between the Jamar hand dynamometer and the WBB was acceptable. Thus, the WBB may be a valid instrument to assess hand grip strength in older adults. PMID- 26842967 TI - Dust mite allergen Der f 4: Expression, characterization, and IgE binding in pediatric asthma. AB - BACKGROUND: House dust mite hypersensitivity affects millions of people worldwide, and although many allergens produced by house dust mite species have been identified, some of the less potent allergens remain to be studied. METHODS: The full-length cDNA encoding the group 4 allergen of the house dust mite species Dermatophagoides farinae (Der f 4) was generated through degenerate primer-based PCR, 5' RACE, and 3' RACE, and the cDNA fragment was cloned into an expression vector for nucleotide sequencing. Following codon optimization and removal of the signal peptide sequence, the mature gene fragment was subcloned into pET-28b (+) and transfected into E. coli BL21 cells for expression. The recombinant protein was purified by nickel affinity chromatography, identified by SDS-PAGE, Western blotting, and MALDI-TOF, and tested by ELISA for IgE reactivity with sera from individuals with asthma. Bioinformatics analyses were used to identify features of Der f 4. RESULTS: SDS-PAGE and Western blotting of the codon-optimized expression product showed a specific band. The mature recombinant Der f 4 was characterized as a stable and hydrophilic 57.9-kDa protein, and its secondary structure comprised alpha helix (25.3%), extended strand (22.51%), and random coils (52.19%). The structure of the recombinant protein was consistent with that of alpha-amylase. Among 27 pediatric asthma patients, 40.74% exhibited reactivity to rDer f 4 by ELISA. CONCLUSIONS: This initial cloning and characterization of the Der f 4 allergen serves as a foundation for future studies into the clinical importance and application of this protein for house dust mite allergy. PMID- 26842968 TI - Ginger augmented chemotherapy: A novel multitarget nontoxic approach for cancer management. AB - Cancer, referred to as the 'disease of civilization', continues to haunt humanity due to its dreadful manifestations and limited success of therapeutic interventions such as chemotherapy in curing the disease. Although effective, chemotherapy has repeatedly demonstrated inadequacy in disease management due to its debilitating side effects arising from its deleterious nonspecific effects on normal healthy cells. In addition, development of chemoresistance due to mono targeting often results in cessation of chemotherapy. This urgently demands development and implementation of multitargeted alternative therapies with mild or no side effects. One extremely promising strategy that yet remains untapped in the clinic is augmenting chemotherapy with dietary phytochemicals or extracts. Ginger, depository of numerous bioactive molecules, not only targets cancer cells but can also mitigate chemotherapy-associated side effects. Consequently, combination therapy involving ginger extract and chemotherapeutic agents may offer the advantage of being efficacious with reduced toxicity. Here we discuss the remarkable and often overlooked potential of ginger extract to manage cancer, the possibility of developing ginger-based combinational therapies, and the major roadblocks along with strategies to overcome them in clinical translation of such inventions. We are optimistic that clinical implementation of such combination regimens would be a much sought after modality in cancer management. PMID- 26842969 TI - The comparative role of echocardiography and MRI for identifying critical lesions in patients with single-ventricle physiology, before bidirectional cavopulmonary connection. AB - BACKGROUND: In the era of multi-modality imaging, this study compared contemporary, pre-operative echocardiography and cardiac MRI in predicting the need for intervention on additional lesions before surgical bidirectional cavopulmonary connection. METHODS: A total of 72 patients undergoing bidirectional cavopulmonary connection for single-ventricle palliation between 2007 and 2012, who underwent pre-operative assessment using both echocardiography and MRI, were included. The pre-determined outcome measure was any additional surgical or catheter-based intervention within 6 months of bidirectional cavopulmonary connection. Indices assessed were as follows: indexed dimensions of right and left pulmonary arteries, coarctation of the aorta, adequacy of interatrial communication, and degree of atrioventricular valve regurgitation. RESULTS: Median age at bidirectional cavopulmonary connection was 160 days (interquartile range 121-284). The following MRI parameters predicted intervention: Z score for right pulmonary artery (odds ratio 1.77 (95% confidence interval 1.12-2.79, p=0.014)) and left pulmonary artery dimensions (odds ratio 1.45 (1.04-2.00, p=0.027)) and left pulmonary artery report conclusion (odds ratio 1.57 (1.06-2.33)). The magnetic resonance report predicted aortic arch intervention (odds ratio 11.5 (3.5-37.7, p=0.00006)). The need for atrioventricular valve repair was associated only with magnetic resonance regurgitation fraction score (odds ratio 22.4 (1.7-295.1, p=0.018)). Echocardiography assessment was superior to MRI for predicting intervention on interatrial septum (odds ratio 27.7 (6.3-121.6, p=0.00001)). CONCLUSION: For branch pulmonary arteries, aortic arch, and atrioventricular valve regurgitation, MRI parameters more reliably predict the need for intervention; however, echocardiography more accurately identified the adequacy of interatrial communication. Approaching bidirectional cavopulmonary connection, the diagnostic strengths of MRI and echocardiography should be acknowledged when considering intervention. PMID- 26842970 TI - Video training with peer feedback in real-time consultation: acceptability and feasibility in a general-practice setting. AB - OBJECTIVE: Since many years, teaching and training in communication skills are cornerstones in the medical education curriculum. Although video recording in a real-time consultation is expected to positively contribute to the learning process, research on this topic is scarce. This study will focus on the feasibility and acceptability of video recording during real-time patient encounters performed by general practitioner (GP) trainees. METHOD: The primary research question addressed the experiences (defined as feasibility and acceptability) of GP trainees in video-recorded vocational training in a general practice. The second research question addressed the appraisal of this training. The procedure of video-recorded training is developed, refined and validated by the Academic Teaching Practice of Leuven since 1974 (Faculty of Medicine of the University of Leuven). The study is set up as a cross-sectional survey without follow-up. Outcome measures were defined as 'feasibility and acceptability' (experiences of trainees) of the video-recorded training and were approached by a structured questionnaire with the opportunity to add free text comments. The studied sample consisted of all first-phase trainees of the GP Master 2011-2012 at the University of Leuven. RESULTS: Almost 70% of the trainees were positive about recording consultations. Nevertheless, over 60% believed that patients felt uncomfortable during the video-recorded encounter. Almost 90% noticed an improvement of own communication skills through the observation and evaluation of. Most students (85%) experienced the logistical issues as major barrier to perform video consultations on a regular base. CONCLUSIONS: This study lays the foundation stone for further exploration of the video training in real-time consultations. Both students and teachers on the field acknowledge that the power of imaging is underestimated in the training of communication and vocational skills. The development of supportive material and protocols will lower thresholds. PRACTICE IMPLICATIONS: Time investment for teachers could be tempered by bringing up students to peer tutors and by an accurate scheduling of the video training. The development of supportive material and protocols will lower thresholds. Further research should finally focus on long-term efficacy and efficiency in terms of learning outcomes and on the facilitation of the technical process. PMID- 26842971 TI - The usefulness of cardiopulmonary exercise testing in assessment of patients with suspected coronary artery disease. AB - OBJECTIVE: The aim of this study is to assess different parameters of cardiopulmonary exercise testing that can predict the development of myocardial ischaemia in patients with suspected coronary artery disease (CAD) and to identify the parameters which have more correlation with myocardial ischaemia. STUDY DESIGN: Cross-sectional study. METHODS: In this study, a total of 31 men (mean age 57.23+/-11.09 years) with suggestive symptoms of CAD underwent an exercise stress test with breath-by-breath gas exchange analysis, followed by coronary angiography as the gold standard for diagnosing CAD. RESULTS: The ventilation versus CO2 output (VE/VCO2) peak was significantly different between patients with negative and positive angiography results. Receiver operator characteristic analysis showed an area under the curve of 0.73 for VE/VCO2 peak with diagnostic threshold equal to 35 (95% CI 0.54 to 0.9; p=0.05). Exercise stress testing had sensitivity and specificity of 75% and 40%, respectively. CONCLUSIONS: A change in ventilatory efficiency assessed using the VE/VCO2 peak has the predictive ability to identify exercise-induced myocardial ischaemia. The present study has provided additional evidence of the potential clinical value of cardiopulmonary exercise testing in the diagnosis of CAD. PMID- 26842972 TI - Evaluation of abnormal liver function tests. AB - Incidentally detected abnormality in liver function tests is a common situation encountered by physicians across all disciplines. Many of these patients do not have primary liver disease as most of the commonly performed markers are not specific for the liver and are affected by myriad factors unrelated to liver disease. Also, many of these tests like liver enzyme levels do not measure the function of the liver, but are markers of liver injury, which is broadly of two types: hepatocellular and cholestatic. A combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease, allowing for a targeted investigation approach. Severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter. In this review, we discuss the interpretation of the routinely performed liver tests along with the indications and utility of quantitative tests. PMID- 26842973 TI - New insulins and newer insulin regimens: a review of their role in improving glycaemic control in patients with diabetes. AB - The legacy effect of early good glycaemic control in people with diabetes shows it is associated with reduction of microvascular and macrovascular complications. Insulin therapy is essential and lifesaving in individuals with type 1 diabetes and beneficial for those with type 2 diabetes who fail to achieve optimal glycaemic targets with other classes of glucose-lowering therapies. Since the introduction of insulin analogues, insulin management has changed. This follow-up review attempts to update our earlier publication from 2009 and discusses the role of new insulin analogues and newer insulin regimens. Recognising the advent of new quality and economic initiatives both in the UK and worldwide, this paper reviews current insulin prescribing and the pros and cons of prescribing analogues in comparison to the human insulins that are now gaining more acceptance in everyday clinical practice. PMID- 26842974 TI - Lipid-lowering, hepatoprotective, and atheroprotective effects of the mixture Hong-Qu and gypenosides in hyperlipidemia with NAFLD rats. AB - BACKGROUND: Hyperlipidemia and its complications are among the most harmful of diseases with a worldwide impact, which creates an urgent imperative to find safe and effective drugs for treatment. HG is mainly composed of two kinds of traditional Chinese medicines (TCM), Hong-Qu and gypenosides. Previously, the ingredients of the mixture mainly composed by Hong-Qu and gypenosides (HG) were widely used for purposes of lipid-lowering, antiatherosclerosis effects, and maintaining cardiovascular health in China. The purpose of this study was to determine whether HG provides any benefit to patients with hyperlipidemia. METHODS: Forty-eight adult male Sprague-Dawley rats with fatty liver disease were randomly divided into six groups: normal, model, two positive controls, and two doses of HG-treated groups. The normal rats were fed a basal diet, and the other rats were fed a high-fat diet. Thereafter, the serum lipid profiles, hepatic steatosis, cytokines, enzymes, and relevant mRNA of rats were analyzed in serum, aorta tissue or hepatic tissues, respectively. RESULTS: After 65 days of feeding the high-fat diet to rats, there were significantly disordered serum lipid profiles, elevated oxidative stress biomarkers, and decreased antiinflammatory cytokines in the serum levels. Additionally, aortic foam cell formation was increased. The gene expression levels including hydroxymethylglutaryl-CoA reductase (HMGR), peroxisome proliferator-activated receptor alpha (PPAR-alpha), sterol response element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase-1 (ACC-1) and carnitine palmitoyl transferase-1(CPT-1) in hepatic tissue were also altered by a high-fat diet fed to Sprague-Dawley rats, and HG treatment significantly resolved and normalized these alterations. Moreover, HG not only caused a significant decrease in the lipid drops on the hepatic tissues, but also restored the antioxidant components. CONCLUSION: HG is beneficial for regulating the stability of blood lipids, has atheroprotective characteristics and may prevent nonalcoholic fatty liver disease (NAFLD), providing more than just a theoretical basis for drug research of cardiovascular disease (CVD) treatment. PMID- 26842977 TI - Do cochlear implants play a role in the induction of brain tumors? PMID- 26842975 TI - Trait self-esteem and neural activities related to self-evaluation and social feedback. AB - Self-esteem has been associated with neural responses to self-reflection and attitude toward social feedback but in different brain regions. The distinct associations might arise from different tasks or task-related attitudes in the previous studies. The current study aimed to clarify these by investigating the association between self-esteem and neural responses to evaluation of one's own personality traits and of others' opinion about one's own personality traits. We scanned 25 college students using functional MRI during evaluation of oneself or evaluation of social feedback. Trait self-esteem was measured using the Rosenberg self-esteem scale after scanning. Whole-brain regression analyses revealed that trait self-esteem was associated with the bilateral orbitofrontal activity during evaluation of one's own positive traits but with activities in the medial prefrontal cortex, posterior cingulate, and occipital cortices during evaluation of positive social feedback. Our findings suggest that trait self-esteem modulates the degree of both affective processes in the orbitofrontal cortex during self-reflection and cognitive processes in the medial prefrontal cortex during evaluation of social feedback. PMID- 26842976 TI - Dual contraceptive method use and pregnancy intention among people living with HIV receiving HIV care at six hospitals in Thailand. AB - BACKGROUND: Describe dual contraceptive method use and the intention to become pregnant of people living with HIV (PLHIV) and their partners in Thailand. METHODS: From January 2008-March 2009, we systematically selected a cohort of PLHIV from PLHIV seeking care at five tertiary care hospitals and one community hospital to complete a questionnaire assessing sexual activity, intention to become pregnant, and contraceptive practices at baseline and 12 months after enrollment. Participants received short family planning messages every 2-3 months to promote the use of dual contraceptives and were offered family planning services. RESULTS: A total of 1,388 PLHIV enrolled, their median age was 37 years (IQR 33-43), 898 (64.7%) had a steady partner, and 737 (53.1%) were male. Among those with a steady partner, 862 (96.0%) did not intend to become pregnant; 709 (82.3%) had sex during the previous 3 months, 683 (96.3%) used at least one contraceptive method, and 202 (29.6%) used dual contraceptive methods. Of the 317 PLHIV who used a single contraceptive method at baseline, 66 (20.8%) reported using dual methods at 12 months. Participants at two tertiary care hospitals where coordinators facilitated PLHIV referral between HIV and OB/GYN clinics were more likely than participants at the other hospitals to change from single method to dual method (p <= 0.03). CONCLUSION: Few PLHIV in this study intended to become pregnant; however, only one-fourth used dual contraceptive methods. Integrating an assessment of the intention to become pregnant and strengthening the PLHIV referral systems in family planning services may contribute to higher rates of dual contraceptive use. PMID- 26842978 TI - Mechanisms Underlying the Active Self-Assembly of Microtubule Rings and Spools. AB - Active self-assembly offers a powerful route for the creation of dynamic multiscale structures that are presently inaccessible with standard microfabrication techniques. One such system uses the translation of microtubule filaments by surface-tethered kinesin to actively assemble nanocomposites with bundle, ring, and spool morphologies. Attempts to observe mechanisms involved in this active assembly system have been hampered by experimental difficulties with performing observation during buffer exchange and photodamage from fluorescent excitation. In the present work, we used a custom microfluidic device to remove these limitations and directly study ring/spool formation, including the earliest events (nucleation) that drive subsequent nanocomposite assembly. Three distinct formation events were observed: pinning, collisions, and induced curvature. Of these three, collisions accounted for the majority of event leading to ring/spool formation, while the rate of pinning was shown to be dependent on the amount of photodamage in the system. We further showed that formation mechanism directly affects the diameter and rotation direction of the resultant rings and spools. Overall, the fundamental understanding described in this work provides a foundation by which the properties of motor-driven, actively assembled nanocomposites may be tailored toward specific applications. PMID- 26842979 TI - The role of root size versus root efficiency in phosphorus acquisition in rice. AB - In rice, genotypic differences in phosphorus (P) uptake from P-deficient soils are generally proportional to differences in root biomass or surface area (RSA). It is not known to what extent genotypic variation for root efficiency (RE) exists or contributes to P uptake. We evaluated 196 rice accessions under P deficiency and detected wide variation for root biomass which was significantly associated with plant performance. However, at a given root size, up to 3-fold variation in total biomass existed, indicating that genotypes differed in how efficiently their root system acquired P to support overall plant growth. This was subsequently confirmed, identifying a traditional genotype, DJ123, with 2.5 fold higher RE (32.5 ug P cm(-2) RSA) compared with the popular modern cultivar IR64. A P depletion experiment indicated that RE could not be explained by P uptake kinetics since even IR64 depleted P to <20nM. A genome-wide association study identified loci associated with RE, and in most cases the more common marker type improved RE. This may indicate that modern rice cultivars lost the ability for efficient P uptake, possibly because they were selected under highly fertile conditions. One association detected on chromosome 11 that was present in a small group of seven accessions (including DJ123) improved RE above the level already present in many traditional rice accessions. This subspecies is known to harbor genes enhancing stress tolerance, and DJ123 may thus serve as a donor of RE traits and genes that modern cultivars seem to have lost. PMID- 26842980 TI - Life at the boundary: photosynthesis at the soil-fluid interface. A synthesis focusing on mosses. AB - Mosses are among the earliest branching embryophytes and probably originated not later than the early Ordovician when atmospheric CO2 was higher and O2 was lower than today. The C3 biochemistry and physiology of their photosynthesis suggests, by analogy with tracheophytes, that growth of extant bryophytes in high CO2 approximating Ordovician values would increase the growth rate. This occurs for many mosses, including Physcomitrella patens in suspension culture, although recently published transcriptomic data on this species at high CO2 and present day CO2 show down-regulation of the transcription of several genes related to photosynthesis. It would be useful if transcriptomic (and proteomic) data comparing growth conditions are linked to measurements of growth and physiology on the same, or parallel, cultures. Mosses (like later-originating embryophytes) have been subject to changes in bulk atmospheric CO2 and O2 throughout their existence, with evidence, albeit limited, for positive selection of moss Rubisco. Extant mosses are subject to a large range of CO2 and O2 concentrations in their immediate environments, especially aquatic mosses, and mosses are particularly influenced by CO2 generated by, and O2 consumed by, soil chemoorganotrophy from organic C produced by tracheophytes (if present) and bryophytes. PMID- 26842982 TI - Plant basal resistance to nematodes: an update. AB - Most plant-parasitic nematodes are obligate biotrophs feeding on the roots of their hosts. Whereas ectoparasites remain on the root surface and feed on the outer cell layers, endoparasitic nematodes enter the host to parasitize cells around or within the central cylinder. Nematode invasion and feeding causes tissue damage which may, in turn, lead to the activation of host basal defence responses. Hitherto, research interests in plant-nematode interaction have emphasized effector-triggered immunity rather than basal plant defence responses. However, some recent investigations suggest that basal defence pathways are not only activated but also play an important role in determining interaction outcomes. In this review we discuss the major findings and point out future directions to dissect the molecular mechanisms underlying plant basal defence to nematodes further. PMID- 26842981 TI - Type-f thioredoxins have a role in the short-term activation of carbon metabolism and their loss affects growth under short-day conditions in Arabidopsis thaliana. AB - Redox regulation plays a central role in the adaptation of chloroplast metabolism to light. Extensive biochemical analyses in vitro have identified f-type thioredoxins (Trxs) as the most important catalysts for light-dependent reduction and activation of the enzymes of the Calvin-Benson cycle. However, the precise function of type f Trxs in vivo and their impact on plant growth are still poorly known. To address this issue we have generated an Arabidopsis thaliana double knock-out mutant, termed trxf1f2, devoid of both f1 and f2 Trxs. Despite the essential function previously proposed for f-type Trxs, the visible phenotype of the trxf1f2 double mutant was virtually indistinguishable from the wild type when grown under a long-day photoperiod. However, the Trx f-deficient plants showed growth inhibition under a short-day photoperiod which was not rescued at high light intensity. The absence of f-type Trxs led to significantly lower photosynthetic electron transport rates and higher levels of non-photochemical energy quenching. Notably, the Trx f null mutant suffered from a shortage of photosystem I electron acceptors and delayed activation of carbon dioxide fixation following a dark-light transition. Two redox-regulated Calvin-Benson cycle enzymes, fructose 1,6-bisphosphatase (FBPase) and Rubisco activase, showed retarded and incomplete reduction in the double mutant upon illumination, compared with wild-type plants. These results show that the function of f-type Trxs in the rapid activation of carbon metabolism in response to light is not entirely compensated for by additional plastid redox systems, and suggest that these Trxs have an important role in the light adjustment of photosynthetic metabolism. PMID- 26842983 TI - An apomixis-linked ORC3-like pseudogene is associated with silencing of its functional homolog in apomictic Paspalum simplex. AB - Apomixis in plants consists of asexual reproduction by seeds. Here we characterized at structural and functional levels an apomixis-linked sequence of Paspalum simplex homologous to subunit 3 of the ORIGIN RECOGNITION COMPLEX (ORC3). ORC is a multiprotein complex which controls DNA replication and cell differentiation in eukaryotes. Three PsORC3 copies were identified, each one characterized by a specific expression profile. Of these, PsORC3a, specific for apomictic genotypes, is a pseudogene that was poorly and constitutively expressed in all developmental stages of apomictic flowers, whereas PsORC3b, the putative functional gene in sexual flowers, showed a precise time-related regulation. Sense transcripts of PsORC3 were expressed in the female cell lineage of both apomictic and sexual reproductive phenotypes, and in aposporous initials. Although strong expression was detected in sexual early endosperm, no expression was present in the apomictic endosperm. Antisense PsORC3 transcripts were revealed exclusively in apomictic germ cell lineages. Defective orc3 mutants of rice and Arabidopsis showed normal female gametophytes although the embryo and endosperm were arrested at early phases of development. We hypothesize that PsORC3a is associated with the down-regulation of its functional homolog and with the development of apomictic endosperm which deviates from the canonical 2(maternal):1(paternal) genome ratio. PMID- 26842984 TI - An ancestral allele of grapevine transcription factor MYB14 promotes plant defence. AB - Stilbene synthase is a key enzyme for the production of the phytoalexin resveratrol. Some clones of Vitis sylvestris, a wild European grapevine species which is almost extinct, have been shown to accumulate more resveratrol in response to different forms of stress. In the current study, we asked whether the induction of stilbene synthase transcripts in Hoe29, one of the V. sylvestris clones with elevated stilbene inducibility, might result from the elevated induction of the transcription factor MYB14. The MYB14 promoter of Hoe29 and of Ke83 (a second stilbene-inducible genotype) harboured distinct regions and were applied to a promoter-reporter system. We show that stilbene synthase inducibility correlates with differences in the induction of MYB14 transcripts for these two genotypes. Both alleles were induced by UV in a promoter-reporter assay, but only the MYB14 promoter from Hoe29 was induced by flg22, consistent with the stilbene synthase expression of the donor genotypes, where both respond to UV but only Hoe29 is responsive to Plasmopara viticola during defence. We mapped upstream signals and found that a RboH-dependent oxidative burst, calcium influx, a MAPK cascade, and jasmonate activated the MYB14 promoter, whereas salicylic acid was ineffective. Our data suggest that the Hoe29 allele of the MYB14 promoter has potential as a candidate target for resistance breeding. PMID- 26842985 TI - Prospective Psychosocial Predictors of Onset and Cessation of Eating Pathology amongst College Women. AB - The course of college women's eating pathology is variable. Little is known about psychosocial factors prospectively predicting maintenance/cessation or the new onset of clinically significant disordered eating symptoms. This study aimed to address these research gaps. College women (N = 2202) completed an assessment of eating pathology and potential risk/maintenance factors at two time points, 9 months apart. Logistic regression models indicated that elevated body dissatisfaction, thin-ideal internalization, self-objectification, negative affectivity and lower self-esteem at baseline predicted 'onset' of clinically significant disordered eating symptomatology at follow-up. Greater self-esteem and lower initial levels on the remaining risk factors predicted subsequent 'cessation' of clinically significant disordered eating symptoms. Self objectification had greater explanatory value with regard to 'cessation' and 'onset' relative to the remaining traditionally accepted factors that demonstrated half as much predictive power or less. Practical implications are discussed. PMID- 26842986 TI - Effects of CpG oligodeoxynucleotide 1826 on acute radiation-induced lung injury in mice. AB - BACKGROUND: The radiation-induced lung injury is a common complication from radiotherapy in lung cancer. CpG ODN is TLR9 activator with potential immune modulatory effects and sensitization of radiotherapy in lung cancer. This study aimed to examine the effect of CpG ODN on acute radiation-induced lung injury in mice. METHODS AND RESULTS: The mouse model of radiation-induced lung injury was established by a single dose of 20 Gy X-rays exposure to the left lung. The results showed that the pneumonia score was lower in RT+CpG group than in RT group on 15th and 30th days. Compared with RT group, CpG ODN reduced the serum concentrations of MDA (P < 0.05) and increased the serum concentrations of SOD, GSH (P < 0.05). The serum concentration of TNF-alpha in RT+CpG group was lower on 15th and 30th days post-irradiation (P < 0.05). CONCLUSION: The study demonstrated that CpG ODN has preventive effects of acute radiation-induced lung injury in mice. Lung inflammatory reaction and oxidative stress are promoted in the initiation of radiation-induced pneumonia. CpG ODN may reduce the injury of reactive oxygen species and adjust the serum TNF-alpha concentration in the mice after irradiation, which reduces the generation of the inflammatory cytokines. PMID- 26842988 TI - Journal of Genetics and Genomics in Transition. PMID- 26842987 TI - Changes in resting state functional connectivity after repetitive transcranial direct current stimulation applied to motor cortex in fibromyalgia patients. AB - BACKGROUND: Fibromyalgia (FM) is a chronic, centralized pain condition characterized by alterations in the functional, chemical, and structural brain networks responsible for sensory and mood processing. Transcranial direct current stimulation (tDCS) has emerged as a potential treatment for FM. tDCS can alter functional connectivity (FC) in brain regions underneath and distant to the stimulating electrode, although the analgesic mechanisms of repetitive tDCS remain unknown. The aim of this study was to investigate how a clinically relevant schedule of tDCS sessions alters resting state FC and how these changes might relate to clinical pain. METHODS: Resting state functional magnetic resonance imaging data were collected from 12 patients with FM at baseline, after 5 days of sham treatment, and after 5 days of real tDCS with the anode over the left primary motor cortex (M1) and the cathode over the right supraorbital cortex. Seed to whole-brain FC analyses were performed with seed regions placed in bilateral M1, primary somatosensory cortices (S1), ventral lateral (VL) and ventral posterolateral (VPL) thalami, and periaqueductal gray (PAG). RESULTS: Stronger baseline FC between M1-VL thalamus, S1-anterior insula, and VL thalamus PAG predicted greater analgesia after sham and real tDCS. Sham treatment (compared with baseline) reduced FC between the VPL thalamus, S1, and the amygdala. Real tDCS (compared with sham treatment) reduced FC between the VL thalamus, medial prefrontal, and supplementary motor cortices. Interestingly, decreased FC between the VL/VPL thalamus and posterior insula, M1, and S1 correlated with reductions in clinical pain after both sham and active treatments. CONCLUSIONS: These results suggest that while there may be a placebo response common to both sham and real tDCS, repetitive M1 tDCS causes distinct changes in FC that last beyond the stimulation period and may produce analgesia by altering thalamic connectivity. PMID- 26842991 TI - Efficiency and Inheritance of Targeted Mutagenesis in Maize Using CRISPR-Cas9. AB - CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR associated proteins) is an adaptive immune system in bacteria and archaea to defend against invasion from foreign DNA fragments. Recently, it has been developed as a powerful targeted genome editing tool for a wide variety of species. However, its application in maize has only been tested with transiently expressed somatic cells or with a limited number of stable transgenic T0 plants. The exact efficiency and specificity of the CRISPR/Cas system in the highly complex maize genome has not been documented yet. Here we report an extensive study of the well-studied type II CRISPR-Cas9 system for targeted genome editing in maize, with the codon-optimized Cas9 protein and the short non-coding guide RNA generated through a functional maize U6 snRNA promoter. Targeted gene mutagenesis was detected for 90 loci by maize protoplast assay, with an average cleavage efficiency of 10.67%. Stable knockout transformants for maize phytoene synthase gene (PSY1) were obtained. Mutations occurred in germ cells can be stably inherited to the next generation. Moreover, no off-target effect was detected at the computationally predicted putative off-target loci. No significant difference between the transcriptomes of the Cas9 expressed and non expressed lines was detected. Our results confirmed that the CRISPR-Cas9 could be successfully applied as a robust targeted genome editing system in maize. PMID- 26842989 TI - The Impact of Genomic Profiling for Novel Cancer Therapy--Recent Progress in Non Small Cell Lung Cancer. AB - There is high expectation for significant improvements in cancer patient care after completion of the human genome project in 2003. Through pains-taking analyses of genomic profiles in cancer patients, a number of targetable gene alterations have been discovered, with some leading to novel therapies, such as activating mutations of EGFR, BRAF and ALK gene fusions. As a result, clinical management of cancer through targeted therapy has finally become a reality for a subset of cancers, such as lung adenocarcinomas and melanomas. In this review, we summarize how gene mutation discovery leads to new treatment strategies using non small cell lung cancer (NSCLC) as an example. We also discuss possible future implications of cancer genome analyses. PMID- 26842990 TI - Drosophila Homolog of FMRP Maintains Genome Integrity by Interacting with Piwi. AB - Fragile X syndrome (FraX), the most common form of inherited mental retardation, is caused by the absence of the evolutionally conserved fragile X mental retardation protein (FMRP). While neuronal functions of FMRP have been intensively studied for the last two decades, its role in non-neuronal cells remains poorly understood. Piwi, a key component of the Piwi-interacting RNA (piRNA) pathway, plays an essential role in germline development. In the present study, we report that similar to piwi, dfmr1, the Drosophila homolog of human FMR1, is required for transposon suppression in the germlines. Genetic analyses showed that dfmr1 and piwi act synergistically in heterochromatic silencing, and in inhibiting the differentiation of primordial germline cells and transposon expression. Northern analyses showed that roo piRNA expression levels are reduced in dfmr1 mutant ovaries, suggesting a role of dfmr1 in piRNA biogenesis. Biochemical analysis demonstrated a physical interaction between dFMRP and Piwi via their N-termini. Taken together, we propose that dFMRP cooperates with Piwi in maintaining genome integrity by regulating heterochromatic silencing in somatic cells and suppressing transposon activity via the piRNA pathway in germlines. PMID- 26842992 TI - Efficient Targeted Genome Modification in Maize Using CRISPR/Cas9 System. AB - CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system, which is a newly developed technology for targeted genome modification, has been successfully used in a number of species. In this study, we applied this technology to carry out targeted genome modification in maize. A marker gene Zmzb7 was chosen for targeting. The sgRNA-Cas9 construct was transformed into maize protoplasts, and indel (insertion and deletion) mutations could be detected. A mutant seedling with an expected albino phenotype was obtained from screening 120 seedlings generated from 10 callus events. Mutation efficiency in maize heterochromatic regions was also investigated. Twelve sites with different expression levels in maize centromeres or pericentromere regions were selected. The sgRNA-Cas9 constructs were transformed into protoplasts followed by sequencing the transformed protoplast genomic DNA. The results show that the genes in heterochromatic regions could be targeted by the CRISPR/Cas9 system efficiently, no matter whether they are expressed or not. Meanwhile, off-target mutations were not found in the similar sites having no PAM (protospacer adjacent motif) or having more than two mismatches. Together, our results show that the CRISPR/Cas9 system is a robust and efficient tool for genome modification in both euchromatic and heterochromatic regions in maize. PMID- 26842993 TI - Characterization of Three Novel Wheat-Thinopyrum intermedium Addition Lines with Novel Storage Protein Subunits and Resistance to Both Powdery Mildew and Stripe Rust. PMID- 26842994 TI - Counting the platelets: a robust and sensitive quantification method for thrombus formation. AB - Flow chambers are common tools used for studying thrombus formation in vitro. However, the use of such devices is not standardised and there is a large diversity among the flow chamber systems currently used, and also in the methods used for quantifying the thrombus development. It was the study objective to evaluate a new method for analysis and quantification of platelet thrombus formation that can facilitate comparison of results between research groups. Whole blood was drawn over a collagen patch in commercial Ibid or in-house constructed PDMS flow chambers. Five percent of the platelets were fluorescently labelled and z-stack time-lapse images were captured during thrombus formation. Images were processed in a Python script in which the number of platelets and their respective x-, y- and z-positions were obtained. For comparison with existing methods the platelets were also labelled and quantified using fluorescence intensity and thrombus volume estimations by confocal microscopy. The presented method was found less sensitive to microscope and image adjustments and provides more details on thrombus development dynamics than the methods for measuring fluorescence intensity and thrombus volume estimation. The platelet count method produced comparable results with commercial and PDMS flow chambers, and could also obtain information regarding the stability of each detected platelet in the thrombus. In conclusion, quantification of thrombus formation by platelet count is a sensitive and robust method that enables measurement of platelet accumulation and platelet stability in an absolute scale that could be used for comparisons between research groups. PMID- 26842996 TI - Hamadaea flava sp. nov., isolated from a soil sample and emended description of the genus Hamadaea. AB - A Gram-stain-positive, aerobic and non-motile actinobacterial strain, designated YIM C0533T, was isolated from a soil sample collected from Shiling county, Yunnan province, south-west China. The isolate grew at 15-37 degrees C, pH 6.0-8.0 and in the presence of 0-3% (w/v) NaCl. The whole-cell hydrolysates contained meso diaminopimelic acid, xylose, galactose, mannose, ribose, arabinose, glucose and rhamnose. The acyl type of muramic acid was glycolyl. The polar lipids detected were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside and an unidentified phospholipid. The major cellular fatty acids were iso-C16:0, 10-methyl C17:0 and iso-C15 : 0.MK-9(H6) was the predominant menaquinone. The genomic DNA G+C content was determined to be 69.4 mol%. These chemotaxonomic data and the morphological properties were consistent with those of the genus Hamadaea. The strain showed highest sequence similarities to Hamadaea tsunoensis CGMCC 4.1403T on phylogenetic analysis of 16S rRNA gene sequences and was found to form a coherent cluster in the neighbour-joining tree. The DNA-DNA hybridization experiment indicated that the DNA-DNA relatedness value between strain YIM C0533T and H. tsunoensis CGMCC 4.1403T was 34.4+/-1.3 %. In addition, the results of physiological and biochemical tests allowed the isolate to be differentiated phenotypically from H. tsunoensis CGMCC 4.1403T. On the basis of data from this polyphasic study, strain YIM C0533T is characterized as a novel species of the genus Hamadaea, for which the name Hamadaea flava sp. nov. is proposed. The type strain is YIM C0533T (=CPCC 204160T=KCTC 39591T=CGMCC 4.7289T). An emended description of the genus Hamadaea is also provided. PMID- 26842995 TI - Visual input to the mouse lateral posterior and posterior thalamic nuclei: photoreceptive origins and retinotopic order. AB - KEY POINTS: The lateral posterior and posterior thalamic nuclei have been implicated in aspects of visually guided behaviour and reflex responses to light, including those dependent on melanopsin photoreception. Here we investigated the extent and basic properties of visually evoked activity across the mouse lateral posterior and posterior thalamus. We show that a subset of retinal projections to these regions derive from melanopsin-expressing retinal ganglion cells and find many cells that exhibit melanopsin-dependent changes in firing. We also show that subsets of cells across these regions integrate signals from both eyes in various ways and that, within the lateral posterior thalamus, visual responses are retinotopically ordered. ABSTRACT: In addition to the primary thalamocortical visual relay in the lateral geniculate nuclei, a number of other thalamic regions contribute to aspects of visual processing. Thus, the lateral posterior thalamic nuclei (LP/pulvinar) appear important for various functions including determining visual saliency, visually guided behaviours and, alongside dorsal portions of the posterior thalamic nuclei (Po), multisensory processing of information related to aversive stimuli. However, despite the growing importance of mice as a model for understanding visual system organisation, at present we know very little about the basic visual response properties of cells in the mouse LP or Po. Prompted by earlier suggestions that melanopsin photoreception might be important for certain functions of these nuclei, we first employ specific viral tracing to show that a subset of retinal projections to the LP derive from melanopsin-expressing retinal ganglion cells. We next use multielectrode electrophysiology to demonstrate that LP and dorsal Po cells exhibit a variety of responses to simple visual stimuli including two distinct classes that express melanopsin-dependent changes in firing (together comprising ~25% of neurons we recorded). We also show that subgroups of LP/Po cells integrate signals from both eyes in various ways and that, within the LP, visual responses are retinotopically ordered. Together our data reveal a diverse population of visually responsive neurons across the LP and dorsal Po whose properties align with some of the established functions of these nuclei and suggest new possible routes through which melanopsin photoreception could contribute to reflex light responses and/or higher order visual processing. PMID- 26842997 TI - Sustained hole inversion layer in a wide-bandgap metal-oxide semiconductor with enhanced tunnel current. AB - Wide-bandgap, metal-oxide thin-film transistors have been limited to low-power, n type electronic applications because of the unipolar nature of these devices. Variations from the n-type field-effect transistor architecture have not been widely investigated as a result of the lack of available p-type wide-bandgap inorganic semiconductors. Here, we present a wide-bandgap metal-oxide n-type semiconductor that is able to sustain a strong p-type inversion layer using a high-dielectric-constant barrier dielectric when sourced with a heterogeneous p type material. A demonstration of the utility of the inversion layer was also investigated and utilized as the controlling element in a unique tunnelling junction transistor. The resulting electrical performance of this prototype device exhibited among the highest reported current, power and transconductance densities. Further utilization of the p-type inversion layer is critical to unlocking the previously unexplored capability of metal-oxide thin-film transistors, such applications with next-generation display switches, sensors, radio frequency circuits and power converters. PMID- 26842998 TI - [Principles and applications of susceptibility weighted imaging]. AB - BACKGROUND: Susceptibility-weighted imaging (SWI), initially developed to provide an improved method for cerebral magnetic resonance (MR) venography, is now an integral part of neuroradiological diagnostics and is steadily gaining importance in non-cerebral imaging. PRINCIPLES: Tissue-inherent susceptibility differences generate a local magnetic field in which the dephasing of signal-producing protons occurs. This leads to a characteristic phase shift that can be used as a means to enhance contrast in the well-known T2*-weighted imaging. APPLICATION IN CLINICAL ROUTINE: Many medically relevant pathologies induce tissue alterations that also influence the magnetic properties of tissue. Thus, the detection of blood residues and calcifications in SWI is superior to conventional MR sequences. FUTURE PROSPECTS: New techniques, such as quantitative susceptibility mapping (QSM) and susceptibility tensor imaging (STI) allow improved differentiation between blood residues and calcifications and provide an alternative imaging method for fiber tractography with respect to diffusion tensor imaging. PMID- 26842999 TI - [Stent-assisted recanalization of femoropopliteal arterial occlusive disease. Influence of stent design on patency rates]. AB - BACKGROUND: Despite enormous technical progress the results of endovascular treatment of the femoropopliteal vasculature are unsatisfactory and its role is still controversially discussed. In the past decade numerous new stent designs have come onto the market but it is unclear whether they have benefits with respect to patency rates. OBJECTIVES: Comparison of published data on patency rates and target lesion revascularization rates after use of different stent designs in the femoropopliteal vasculature. MATERIAL AND METHODS: Analysis of 25 published studies and registries from 2006 to 2015 for classical open-cell stents, interwoven stents and partially or fully covered stents. RESULTS AND CONCLUSION: The published data are heterogeneous and comparative studies for different stent designs are completely missing. Over the past decade the patency rates after femoropopliteal stenting could be improved. According to available data stenting of short lesions < 5 cm does not show any benefit compared to isolated balloon angioplasty. Primary stenting is now recommended for intermediate and longer lesions > 6.4 cm. Due to the heterogeneity of published data a clear benefit for a specific stent design is not obvious; however, data for interwoven stents are promising and show a tendency towards improved patency, at least for certain lesions. Randomized controlled comparative trials are needed to confirm this result. PMID- 26843000 TI - Evaluation of the cause of unexplained radiocaesium contamination of brown rice in Fukushima in 2013 using autoradiography and gamma-ray spectrometry. AB - The Great East Japan Earthquake on 11 March 2011, caused the release of radioactive materials from the Fukushima Daiichi Nuclear Power Plant (FDNPP), contaminating eastern Japan, particularly in part of Fukushima Prefecture. In 2012 and 2014, the radiocaesium concentration in brown rice did not exceed regulatory levels in Minamisoma City, Fukushima. However, in 2013, some radiocaesium concentrations in brown rice exceeded regulatory levels. In this work, autoradiograms showed that high radioactivity was present as contaminated spots on the panicles of rice and in brown rice in 2013. We evaluate the contribution of direct contamination to the radiocaesium concentration in brown rice and discuss the origin of radiocaesium contamination in brown rice using the (134)Cs/(137)Cs radioactivity ratio. Here, we show that the main cause of the unexplained radiocaesium contamination of brown rice in Minamisoma City in 2013 is the adherence of radioactive materials to the rice panicles, and these radioactive materials are associated with reactor units 2 or 3 of FDNPP. PMID- 26843001 TI - Prefrontal activation may predict working-memory training gain in normal aging and mild cognitive impairment. AB - Cognitive training has been shown to result in improved behavioral performance in normal aging and mild cognitive impairment (MCI), yet little is known about the neural correlates of cognitive plasticity, or about individual differences in responsiveness to cognitive training. In this study, 21 healthy older adults and 14 patients with MCI received five weeks of adaptive computerized working-memory (WM) training. Before and after training, functional Near-Infrared Spectroscopy (fNIRS) was used to assess the hemodynamic response in left and right prefrontal cortex during performance of a verbal n-back task with varying levels of WM load. After training, healthy older adults demonstrated decreased prefrontal activation at high WM load, which may indicate increased processing efficiency. Although MCI patients showed improved behavioral performance at low WM load after training, no evidence was found for training-related changes in prefrontal activation. Whole group analyses showed that a relatively strong hemodynamic response at low WM load was related to worse behavioral performance, while a relatively strong hemodynamic response at high WM load was related to higher training gain. Therefore, a 'youth-like' prefrontal activation pattern at older age may be associated with better behavioral outcome and cognitive plasticity. PMID- 26843003 TI - Incidental findings on brain magnetic resonance imaging in the elderly:the PROOF study. AB - To prospectively evaluate the prevalence of incidental findings on standardized brain MRI scans in a cohort of elderly subjects. All participants provided written informed consent to participate in this prospective study, which was approved by the institutional review board and was HIPAA compliant. There were 503 subjects (75.3 +/- 0.9 years of age, 58 % women) who received brain MRIs on a 1.5-T scanner using a standard acquisition protocol. All scans were reviewed by an experienced neuroradiologist. Incidental findings were stratified as follows: 1, no incidental findings; 2, incidental findings without clinical significance; 3, incidental findings with clinical significance or requiring clinical follow up. Incidental findings were identified in 77.9 % of subjects. Among 392 scans that exhibited incidental findings, 494 abnormalities were identified. The most common findings in our study were cysts (45.9 % of subjects) and ear, nose, and throat (ENT) lesions (24.8 %) followed by stroke lesions (6.6 %) and neoplasms (3.8 %). There were 472 incidental findings that lacked clinical significance (group 2), and 22 incidental findings that required follow-up evaluation (group 3). Incidental findings on brain MRIs were commonly observed in this cohort of elderly subjects, but clinical follow-up was rarely indicated. PMID- 26843002 TI - Altered resting state functional connectivity of anterior insula in young smokers. AB - The insula has been implicated in cognitive control and craving, all of which are critical to the clinical manifestations of nicotine dependence. However, little evidence exists about the abnormalities in resting state functional connectivity (RSFC) of the insula in young smokers, which might improve our understanding of the neural mechanisms of nicotine dependence. Due to the structural and functional heterogeneity of the insula, the RSFC patterns of both left and right anterior (AI) and posterior insula (PI) were investigated in young smokers and non-smokers. Meanwhile, the relationship was assessed between the neuroimaging findings and clinical information (pack-years, FTND, and craving) as well as cognitive control deficits measured by Stroop task performance. Compared with non smokers, young smokers showed reduced RSFC between right AI and anterior cingulate cortex (ACC), ventromedial prefrontal cortex (VMPFC), amygdala, left dorsolateral prefrontal cortex, and dorsal striatum. Additionally, left AI showed reduced RSFC with ACC. Both left and right PI network differences were not observed between two groups. Moreover, in young smokers, FTND and incongruent errors in the Stroop task were negatively correlated with the RSFC between AI and ACC. Craving scores showed a significantly negative relationship with the RSFC strength between right AI and left VMPFC. These results provide a more thorough network-level understanding the role of insula in cigarette smoking. The findings provide new insights into the roles of AI-ACC circuit in cognitive control deficits and right AI-VMPFC circuit relevant to the craving of nicotine dependence for young smokers. PMID- 26843005 TI - Aberrant regional homogeneity of resting-state executive control, default mode, and salience networks in adult patients with moyamoya disease. AB - Aberrant local connectivity within cerebral intrinsic connectivity networks (ICNs) at rest has not been reported in adult moyamoya disease (MMD). Our aim was to examine the regional homogeneity (ReHo) of executive control (ECN), default mode (DMN), and salience networks (SN) in patients with executive dysfunction to explore the underlying mechanism. Twenty-six adult patients with MMD and 24 normal control (NC) subjects were recruited. Executive function was evaluated by Trail Making Test Part B (TMT-B) and executive subtests of Memory and Executive Screening (MES-EX). Compared with NC, the case group exhibited ReHo decrease mainly in the frontal and parietal gyrus, and increase only in the left middle temporal gyrus. Subsequent ICNs analysis indicated that compared with NC, patients with MMD exhibited significantly decreased ReHo in the dorsolateral prefrontal cortex (DLPFC) and inferior parietal gyrus (IPG) of left ECN; the IPG, superior frontal gyrus, and DLPFC of the right ECN; the right precuneus, left medial superior frontal gyrus, and right medial orbitofrontal gyrus of the DMN; as well as the left middle frontal gyrus and right supplemental motor area of SN. When referring to the Suzuki's 6-stage classification, a trend of ReHo decrease with disease severity was observed in all of the ICNs examined, but only bilateral ECNs reached statistical significance. Finally, only bilateral ECNs exhibited a significant correlation of averaged ReHo values with executive performance. Our results provide new insight into the pathophysiology of adult MMD. PMID- 26843004 TI - Neural correlates of dystonic tremor: a multimodal study of voice tremor in spasmodic dysphonia. AB - Tremor, affecting a dystonic body part, is a frequent feature of adult-onset dystonia. However, our understanding of dystonic tremor pathophysiology remains ambiguous as its interplay with the main co-occurring disorder, dystonia, is largely unknown. We used a combination of functional MRI, voxel-based morphometry and diffusion-weighted imaging to investigate similar and distinct patterns of brain functional and structural alterations in patients with dystonic tremor of voice (DTv) and isolated spasmodic dysphonia (SD). We found that, compared to controls, SD patients with and without DTv showed similarly increased activation in the sensorimotor cortex, inferior frontal (IFG) and superior temporal gyri, putamen and ventral thalamus, as well as deficient activation in the inferior parietal cortex and middle frontal gyrus (MFG). Common structural alterations were observed in the IFG and putamen, which were further coupled with functional abnormalities in both patient groups. Abnormal activation in left putamen was correlated with SD onset; SD/DTv onset was associated with right putaminal volumetric changes. DTv severity established a significant relationship with abnormal volume of the left IFG. Direct patient group comparisons showed that SD/DTv patients had additional abnormalities in MFG and cerebellar function and white matter integrity in the posterior limb of the internal capsule. Our findings suggest that dystonia and dystonic tremor, at least in the case of SD and SD/DTv, are heterogeneous disorders at different ends of the same pathophysiological spectrum, with each disorder carrying a characteristic neural signature, which may potentially help development of differential markers for these two conditions. PMID- 26843006 TI - The effects of DAT1 genotype on fMRI activation in an emotional go/no-go task. AB - Dopaminergic brain circuits participate in emotional processing and impulsivity. The dopamine transporter (DAT) modulates dopamine reuptake. A variable number tandem repeat (VNTR) in the dopamine transporter gene (DAT1) affects DAT expression. The influence of DAT1 genotype on neural activation during emotional processing and impulse inhibition has not been examined. Forty-two healthy subjects were classified as 9DAT (n = 17) or 10DAT (n = 25) based on DAT1 genotype (9DAT = 9R/9R and 9R/10R; 10DAT = 10R/10R). Subjects underwent fMRI during non-emotional and emotional go/no-go tasks. Subjects were instructed to inhibit responses to letters, happy faces, or sad faces in separate blocks. Accuracy and reaction time did not differ between groups. Within group results showed activation in regions previously implicated in emotional processing and response inhibition. Between groups results showed increased activation in 9DAT individuals during inhibition. During letter inhibition, 9DAT individuals exhibited greater activation in right inferior parietal regions. During sad inhibition, 9DAT Individuals exhibited greater activation in frontal, posterior cingulate, precuneus, right cerebellar, left paracentral, and right occipital brain regions. The interaction between DAT genotype and response type in sad versus letter stimuli showed increased activation in 9DAT individuals during sad no-go responses in the anterior cingulate cortex, extending into frontal-orbital regions. 9DAT individuals have greater activation than 10DAT individuals during neutral and sad inhibition, showing that genotypic variation influencing basal dopamine levels can alter the neural basis of emotional processing and response inhibition. This may indicate that 9R carriers exert more effort to overcome increased basal dopamine activation when inhibiting responses in emotional contexts. PMID- 26843007 TI - APOE epsilon4 associated with preserved executive function performance and maintenance of temporal and cingulate brain volumes in younger adults. AB - The APOE epsilon4 allele is associated with cognitive deficits and brain atrophy in older adults, but studies in younger adults are mixed. We examined APOE genotype effects on cognition and brain structure in younger adults and whether genotype effects differed by age and with presence of depression. 157 adults (32 % epsilon4 carriers, 46 % depressed) between 20 and 50 years of age completed neuropsychological testing, 131 of which also completed 3 T cranial MRI. We did not observe a direct effect of APOE genotype on cognitive performance or structural MRI measures. A significant genotype by age interaction was observed for executive function, where age had less of an effect on executive function in epsilon4 carriers. Similar interactions were observed for the entorhinal cortex, rostral and caudal anterior cingulate cortex and parahippocampal gyrus, where the effect of age on regional volumes was reduced in epsilon4 carriers. There were no significant interactions between APOE genotype and depression diagnosis. The epsilon4 allele benefits younger adults by allowing them to maintain executive function performance and volumes of cingulate and temporal cortex regions with aging, at least through age fifty years. PMID- 26843008 TI - Sex differences in the association between AD biomarkers and cognitive decline. AB - Women are disproportionately affected by Alzheimer's disease (AD) in terms of both disease prevalence and severity. Previous autopsy work has suggested that, in the presence of AD neuropathology, females are more susceptible to the clinical manifestation of AD. This manuscript extends that work by evaluating whether sex alters the established associations between cerebrospinal fluid (CSF) biomarker levels and brain aging outcomes (hippocampal volume, cognition). Participants were drawn from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and included individuals with normal cognition (n = 348), mild cognitive impairment (n = 565), and AD (n = 185). We leveraged mixed effects regression models to assess the interaction between sex and baseline cerebrospinal fluid biomarker levels of amyloid-beta42 (Abeta-42) and total tau on cross-sectional and longitudinal brain aging outcomes. We found a significant interaction between sex and Abeta-42 on longitudinal hippocampal atrophy (p = 0.002), and longitudinal decline in memory (p = 0.017) and executive function (p = 0.025). Similarly, we observed an interaction between sex and total tau level on longitudinal hippocampal atrophy (p = 0.008), and longitudinal decline in executive function (p = 0.034). Women with Abeta-42 and total tau levels indicative of worse pathological changes showed more rapid hippocampal atrophy and cognitive decline. The sex difference was particularly pronounced among individuals with MCI, with lower education, and varied by APOE epsilon4 allele. These results suggest females may be more susceptible to the clinical manifestation of AD. PMID- 26843009 TI - Cortical damage in the posterior visual pathway in patients with sialidosis type 1. AB - In order to identify the cortical changes in patients with Sialidosis type 1, diffusion tensor imaging and resting state fMRI were acquired from 11 patients and 11 sex/age matched normal controls after clinical evaluations. The neuroimages from each participant were normalized and parcellated according to the Automatic Anatomical Labeling. Both the mean diffusivity and the corresponding functional connectivity were calculated from each cortical region. The white matter tract integrity was examined. The difference between patients and controls was examined using Student's t-test and between patients with either homozygous or heterozygous mutations by Mann-Whitney U test, both at a threshold of 0.05. Increased mean diffusivity throughout the brain can be noticed in the patients, together with a compromised white matter tracts integrity. The most severely affected cortical regions are in the occipital lobe. Decreased functional connectivity was from the temporal and occipital lobes to the hippocampus and parahippocampus. In contrast, connectivity from thalamus was enhanced. Diffused cortical atrophy with posterior focal lesions was noticed. We concluded that MRI observed functional changes in the posterior cortical pathways in the patients with Sialidosis. The observation might be related to the cortical blindness due to an altered neural network and a compromised visual pathway in the patients. PMID- 26843011 TI - Preoperative axillary lymph node evaluation in breast cancer patients by breast magnetic resonance imaging (MRI): Can breast MRI exclude advanced nodal disease? AB - OBJECTIVES: To evaluate the diagnostic performance of breast magnetic resonance imaging (MRI) in preoperative evaluation of axillary lymph node metastasis (ALNM) in breast cancer patients and to assess whether breast MRI can be used to exclude advanced nodal disease. METHODS: A total of 425 patients were included in this study and breast MRI findings were retrospectively reviewed. The diagnostic performance of breast MRI for diagnosis of ALNM was evaluated in all patients, patients with neoadjuvant chemotherapy (NAC), and those without NAC (no-NAC). We evaluated whether negative MRI findings (cN0) can exclude advanced nodal disease (pN2-pN3) using the negative predictive value (NPV) in each group. RESULTS: The sensitivity and NPV of breast MRI in evaluation of ALNM was 51.3 % (60/117) and 83.3 % (284/341), respectively. For cN0 cases on MRI, pN2-pN3 manifested in 1.8 % (6/341) of the overall patients, 0.4 % (1/257) of the no-NAC group, and 6 % (5/84) of the NAC group. The NPV of negative MRI findings for exclusion of pN2 pN3 was higher for the no-NAC group than for the NAC group (99.6 % vs. 94.0 %, p = 0.039). CONCLUSIONS: Negative MRI findings (cN0) can exclude the presence of advanced nodal disease with an NPV of 99.6 % in the no-NAC group. KEY POINTS: * Breast MRI can be used to exclude advanced nodal disease (pN2-3). * Negative MRI allows breast cancer patients to avoid unnecessary axillary surgery (98.2 %). * Negative MRI findings exclude 99.6 % of pN2-pN3 in the no-NAC group. * Negative MRI findings exclude 96.0 % of pN2-pN3 in the NAC group. PMID- 26843010 TI - Lung morphology assessment of cystic fibrosis using MRI with ultra-short echo time at submillimeter spatial resolution. AB - OBJECTIVES: We hypothesized that non-contrast-enhanced PETRA (pointwise encoding time reduction with radial acquisition) MR (magnetic resonance) sequencing could be an alternative to unenhanced computed tomography (CT) in assessing cystic fibrosis (CF) lung structural alterations, as well as compared agreements and concordances with those of conventional T1-weighted and T2-weighted sequences. MATERIAL AND METHODS: Thirty consecutive CF patients completed both CT and MRI the same day. No contrast injection was used. Agreement in identifying structural alterations was evaluated at the segmental level using a kappa test. Intraclass correlation coefficients (ICC) and Bland-Altman analysis were used to assess concordances and reproducibility in Helbich-Bhalla disease severity scoring. RESULTS: Agreement between PETRA and CT was higher than that of T1- or T2 weighted sequences, notably in assessing the segmental presence of bronchiectasis (Kappa = 0.83; 0.51; 0.49, respectively). The concordance in Helbich-Bhalla scores was very good using PETRA (ICC = 0.97), independently from its magnitude (mean difference (MD) = -0.3 [-2.8; 2.2]), whereas scoring was underestimated using both conventional T1 and T2 sequences (MD = -3.6 [-7.4; 0.1]) and MD = -4.6 [-8.2; -1.0], respectively). Intra- and interobserver reproducibility were very good for all imaging modalities (ICC = 0.86-0.98). CONCLUSION: PETRA showed higher agreement in describing CF lung morphological changes than that of conventional sequences, whereas the Helbich-Bhalla scoring matched closely with that of CT. KEY POINTS: * Spatial resolution of lung MRI is limited using non ultra-short TE MRI technique * Ultra-short echo time (UTE) technique enables submillimeter 3D-MRI of airways * 3D-UTE MRI shows very good concordance with CT in assessing cystic fibrosis * Radiation-free 3D-UTE MRI enables the Helbich Bhalla scoring without a need for contrast injection. PMID- 26843013 TI - Discovery and Structure-Activity Relationship Study of 4-Phenoxythiazol-5 carboxamides as Highly Potent TGR5 Agonists. AB - A novel therapy that stimulates endogenous glucagon-like peptide-1 (GLP-1) secretion by Takeda G-protein-coupled receptor 5 (TGR5) agonists might be a superior alternative for the treatment of type 2 diabetes mellitus. A series of 4 phenoxythiazol-5-carboxamides were developed as highly potent TGR5 agonists using a bioisosteric replacement strategy based on the scaffold of 4 phenoxynicotinamides. The structure-activity relationship on the bottom phenyl ring and the thiazole ring was extensively studied, and the 2-methyl-thiazole derivatives 30c and e displayed the best in vitro potency toward human TGR5, with EC50 values of approximately 1 nM. While endowed with excellent in vitro potency, the 2-methyl-thiazoles were flawed with high microsomal clearance. PMID- 26843014 TI - Selection of quality indicators for hospital-based emergency care in Denmark, informed by a modified-Delphi process. AB - BACKGROUND: In 2013, Danish policy-makers on a nationwide level decided to set up a national quality of care database for hospital-based emergency care in Denmark including the selection of quality indicators. The aim of the study was to describe the Delphi process that contributed to the selection of quality indicators for a new national database of hospital-based emergency care in Denmark. METHODS: The process comprised a literature review followed by a modified-Delphi survey process, involving a panel of 54 experts (senior clinicians, researchers and administrators from the emergency area and collaborating specialties). Based on the literature review, we identified 43 potential indicators, of which eight were time-critical conditions. We then consulted the Expert panel in two consecutive rounds. The Expert panel was asked to what extent each indicator would be a good measure of hospital-based emergency care in Denmark. In each round, the Expert panel participants scored each indicator on a Likert scale ranging from one (=disagree completely) through to six (=agree completely). Consensus for a quality indicator was reached if the median was greater than or equal to five (=agree). The Delphi process was followed by final selection by the steering group for the new database. RESULTS: Following round two of the Expert panel, consensus was reached on 32 quality indicators, including three time-critical conditions. Subsequently, the database steering group chose a set of nine quality indicators for the initial version of the national database for hospital-based emergency care. CONCLUSIONS: The two round modified Delphi process contributed to the selection of an initial set of nine quality indicators for a new a national database for hospital-based emergency care in Denmark. Final selection was made by the database steering group informed by the Delphi process. PMID- 26843012 TI - Identification of a candidate biomarker from perfusion MRI to anticipate glioblastoma progression after chemoradiation. AB - OBJECTIVE: To identify relevant relative cerebral blood volume biomarkers from T2* dynamic-susceptibility contrast magnetic resonance imaging to anticipate glioblastoma progression after chemoradiation. METHODS: Twenty-five patients from a prospective study with glioblastoma, primarily treated by chemoradiation, were included. According to the last follow-up MRI confirmed status, patients were divided into: relapse group (n = 13) and control group (n = 12). The time of last MR acquisition was tend; MR acquisitions performed at tend-2M, tend-4M and tend 6M (respectively 2, 4 and 6 months before tend) were analyzed to extract relevant variations among eleven perfusion biomarkers (B). These variations were assessed through R(B), as the absolute value of the ratio between ?B from tend-4M to tend 2M and ?B from tend-6M to tend-4M. The optimal cut-off for R(B) was determined using receiver-operating-characteristic curve analysis. RESULTS: The fraction of hypoperfused tumor volume (F_hPg) was a relevant biomarker. A ratio R(F_hPg) >= 0.61 would have been able to anticipate relapse at the next follow-up with a sensitivity/specificity/accuracy of 92.3 %/63.6 %/79.2 %. High R(F_hPg) (>=0.61) was associated with more relapse at tend compared to low R(F_hPg) (75 % vs 12.5 %, p = 0.008). CONCLUSION: Iterative analysis of F_hPg from consecutive examinations could provide surrogate markers to predict progression at the next follow-up. KEY POINTS: * Related rCBV biomarkers from DSC were assessed to anticipate GBM progression. * Biomarkers were assessed through their patterns of variation during the follow-up. * The fraction of hypoperfused tumour volume (F_hP g ) seemed to be a relevant biomarker. * An innovative ratio R(F_hP g ) could be an early surrogate marker of relapse. * A significant time gain could be achieved in the management of GBM patients. PMID- 26843015 TI - A Porous Aromatic Framework Constructed from Benzene Rings Has a High Adsorption Capacity for Perfluorooctane Sulfonate. AB - A low-cost and easily constructed porous aromatic framework (PAF-45) was successfully prepared using the Scholl reaction. PAF-45 was, for the first time, used to remove perfluorooctane sulfonate (PFOS) from aqueous solution. Systematic experiments were performed to determine the adsorption capacity of PAF-45 for PFOS and to characterize the kinetics of the adsorption process. The adsorption of PFOS onto PAF-45 reached equilibrium in 30 min, and the adsorption capacity of PAF-45 for PFOS was excellent (5847 mg g(-1) at pH 3). The amount of PFOS adsorbed by PAF-45 increased significantly as the cation (Na(+), Mg(2+), or Fe(3+)) concentration increased, which probably occurred because the cations enhanced the interactions between the negatively charged PFOS molecules and the positively charged PAF-45 surface. The cations Na(+), Mg(2+), and Fe(3+) were found to form complexes with PFOS anions in solution. Density functional theory was used to identify the interactions between PFOS and Na(+), Mg(2+), and Fe(3+). We expect that materials of the same type as PAF-45 could be useful adsorbents for removing organic pollutants from industrial wastewater and contaminated surface water. PMID- 26843016 TI - Effect of Frailty and Age on Platelet Aggregation and Response to Aspirin in Older Patients with Atrial Fibrillation: A Pilot Study. AB - INTRODUCTION: Frailty is associated with changes in inflammation, coagulation, and possibly platelet function. Aspirin is still prescribed for stroke prevention in older patients with atrial fibrillation, although not recommended by current guidelines. In frail older people, it is unclear whether platelet aggregability and response to aspirin are altered. This study aims to investigate the effects of frailty and chronological age on platelet aggregability and on responses to aspirin in older patients with atrial fibrillation. METHODS: Inpatients with atrial fibrillation aged >=65 years were recruited from a tertiary referral hospital in Sydney, Australia. Frailty was determined using the Reported Edmonton Frail Scale. Platelet aggregation studies were performed using whole blood impedance aggregometry. RESULTS: Data from 115 participants were analyzed (mean age 85 +/- 6 years, 41% female, 52% frail). Spearman correlation coefficients found no significant associations of platelet aggregation with chronological age or with frailty score. Comparison between frail and non-frail groups showed that there was no impact of frailty status on aggregation assays amongst participants who were not taking any antiplatelet drugs. Amongst participants taking aspirin, the frail had higher adjusted arachidonic acid agonist (ASPI) test measures (AU per platelet) than the non-frail (0.11 +/- 0.11 vs. 0.05 +/- 0.04; p = 0.04), suggesting that in frail participants, platelet aggregation is less responsive to aspirin than in non-frail. CONCLUSIONS: We found no effect of chronological age or frailty status on platelet aggregation amongst older patients with atrial fibrillation in this pilot study. However, frailty could be associated with reduced aspirin responsiveness among older patients with atrial fibrillation. PMID- 26843018 TI - Faulty Injection Technique: A Preventable But Often Overlooked Factor in Insulin Allergy. AB - Insulin hypersensitivity-a rare occurrence with currently available insulin preparations-may have varied manifestations, ranging from a local injection site allergy to severe generalized anaphylactic reactions. While various additives included in commercial insulin preparations and insulin peptides themselves remain the primary allergens responsible, faulty injection technique may at times potentiate the development of insulin allergy. Management of insulin allergy is complex, potentially dangerous at times, and can be challenging for the treating physician. We report a case of insulin allergy due to intradermal insulin injections which was cured by adopting a proper injection technique. PMID- 26843017 TI - Development of Novel High-Resolution Melting-Based Assays for Genotyping Two Alu Insertion Polymorphisms (FXIIIB and PV92). AB - Insertion/Deletion polymorphisms (InDels) are a common type of genetic variation, with a growing role in population genetics and applied genomics. There is the need for the development of novel cost-effective assays for genotyping InDels of high importance. The main objective of this study was to develop high-resolution melting-based assays for genotyping two commonly studied Alu insertion polymorphisms: FXIIIB and PV92 (rs70942849 and rs3138523). Three primers (two forward and one reverse) were designed for each marker, and high-resolution melting (HRM) analyses in a qPCR platform were performed, using EvaGreen fluorescent dye. For each one of the two Alu insertion polymorphisms, HRM analyses identified distinguishable peaks for the three genotypes, allowing a robust genotyping. Results were validated using 96 DNA samples previously genotyped and the assays worked with different DNA concentrations. In this study, we developed novel cost-effective assays, using qPCR, for genotyping two Alu insertion polymorphisms (widely used as ancestry markers). Our results highlight the feasibility of using HRM analyses for genotyping InDel polymorphisms of medical and biotechnological importance. PMID- 26843020 TI - Higher levels of mercury in brain are not linked to increased risk of Alzheimer's, study finds. PMID- 26843021 TI - Single frequency intake of alpha-linolenic acid rich phytosterol esters attenuates atherosclerosis risk factors in hamsters fed a high fat diet. AB - BACKGROUND: Emerging evidence suggested phytosterol esters (PE) exhibited an advantage over naturally occurring phytosterols in reducing atherosclerosis risk factors due to improved fat solubility and compatibility. However, the effects of dietary patterns of PE on lipid-lowering activity were limited and inconsistent. This study aimed to explore the effects of dose and frequency of alpha-linolenic acid rich phytosterol esters (ALA-PE) on cholesterol and triglyceride metabolism markers focused on intestinal cholesterol absorption and bioconversion of ALA in liver. METHODS: Dose-dependency study Male Syrian golden hamsters were fed high fat diets (HFD) containing low, medium and high dose of ALA-PE (0.72 %, 2.13 % and 6.39 %) for 6 weeks. The high fat diet contained 89.5 % chow diet, 0.2 % cholesterol, 10 % lard and 0.3 % bile salt. Dose-frequency study Male Syrian golden hamsters were provided: (I) 0.4 mL/100 g peanut oil by gavage once a day; (II) 0.4 mL/100 g ALA-PE by gavage once a day; (III) 0.2 mL/100 g ALA-PE by gavage twice a day; (IV) 0.133 mL/100 g ALA-PE by gavage three times a day; (V) 0.1 mL/100 g ALA-PE by gavage four times a day for 6 weeks with a high-fat diet simultaneously. RESULTS: ALA-PE dose-dependently lowered plasma total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) concentrations with a maximal decrease of 42 %, 59 % and 73 %, respectively (p < 0.05). Compared to HFD, TC, LDL-C and TG concentrations were significantly lower (p < 0.01) in hamsters consumed HFD plus ALA-PE for 1-4 times per day but there were not remarkable differences among different consumption frequencies. No significant changes in plasma antioxidant capacity and lipid peroxidation levels were observed among HFD and HFD plus different doses of ALA-PE groups. The contents of hepatic alpha-linolenic (ALA), docosapentaenoic (DPA) and docosahexaenoic (DHA) acids were dose-dependently increased in different ALA-PE groups compared to those in HFD group. The abundance of mRNA for intestinal sterol transporters Niemann-Pick C1-Like 1 (NPC1L1), ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 indicated no significant differences among all groups. CONCLUSION: ALA-PE dose-dependently improved lipid profile in hamsters fed HFD independent of intestinal ABCG5, ABCG8 and NPC1L1, accompanying by increased conversion of ALA to DPA and DHA in liver. ALA-PE manifested "once a day" lipid-lowering efficacy, highlighting a promising preventive strategy for metabolic syndrome. PMID- 26843022 TI - Innervation of the human cricopharyngeal muscle by the recurrent laryngeal nerve and external branch of the superior laryngeal nerve. AB - PURPOSE: The major component of the upper esophageal sphincter is the cricopharyngeal muscle (CPM). We assessed the contribution of the laryngeal nerves to motor innervation of the CPM. METHODS: We performed an intraoperative electromyographic study of 27 patients. The recurrent laryngeal nerve (RLN), vagus nerve, external branch of the superior laryngeal nerve (EBSLN), and pharyngeal plexus (PP) were stimulated. Responses were evaluated by visual observation of CPM contractions and electromyographic examination via insertion of needle electrodes into the CPM. RESULTS: In total, 46 CPMs (24 right, 22 left) were evaluated. PP stimulation produced both positive visual contractions and electromyographic (EMG) responses in 42 CPMs (2080 +/- 1583 MUV). EBSLN stimulation produced visual contractions of 28 CPMs and positive EMG responses in 35 CPMs (686 +/- 630 MUV). Stimulation of 45 RLNs produced visible contractions of 37 CPMs and positive EMG activity in 41 CPMs (337 +/- 280 MUV). Stimulation of 42 vagal nerves resulted in visible contractions of 36 CPMs and positive EMG responses in 37 CPMs (292 +/- 229 MUV). Motor activity was noted in 32 CPMs by both RLN and EBSLN stimulation, 9 CPMs by RLN stimulation, and 3 CPMs by EBSLN stimulation; 2 CPMs exhibited no response. CONCLUSIONS: This is the first study to show that the EBSLN contributes to motor innervation of the human CPM. The RLN, EBSLN, or both of the nerves innervate the 90, 75, and 70 % of the CPMs ipsilaterally, respectively. PMID- 26843023 TI - Three-dimensional volumetric measurements in defining endoscope-guided giant adenoma surgery outcomes. AB - PURPOSE: Maximum two-dimensional (2D) diameter has been used to define giant pituitary adenoma (GPA) surgery outcomes as has volume using an ellipsoid approximation of volumetrics. Cross sectional length can be measured in several different planes. We sought to compare the accuracy of different 2D cross sectional measurements with the 3D volumetric measurements for predicting GPA surgery outcomes. METHODS: Retrospective analysis was performed on a prospectively collected database. Tumors with >3 cm diameter were identified and classified based on maximal cross sectional measurements in three separate co axial planes, i.e. transverse (TV), antero-posterior (AP) and cranio-caudal (CC). Volume was calculated using both MRI-guided volumetrics and an ellipsoid approximation (TV * AP * CC/2). Univariate and multivariate analysis was used to evaluate the relationship between cross sectional and volumetric data and extent of resection (EOR). RESULTS: In 62 subjects, median tumor volume using 3D volumetrics was 13.74 cm(3), which was overestimated by 16 % by the ellipsoid calculation (p = 0.0029), particularly for tumors >20 cm(3). Gross total resection (GTR) was 46.7 % and median EOR was 99.57 %. At 22-month follow-up, visual and anterior pituitary functions were stable (90 %) or improved (87 %). Pre-operative tumor volume >10 cm(3) (p = 0.02) and Knosp grade 3-4 (p = 0.04) were independent predictors of EOR. Knosp grade 3-4 (p < 0.0001), TV measurement >4 cm (p = 0.007) and maximum cross sectional length >4 cm (p = 0.04) were predictors of not achieving GTR. Only TV measurement (p = 0.02) predicted permanent diabetes insipidis. The smallest significant thresholds for predicting decreased GTR were TV measurement >25 mm, AP measurement >35 mm and volume >19 cm(3). CONCLUSION: We propose a new volumetric threshold of 20 cm(3) as most accurate for predicting GTR in the EEA era. CC measurement is the least useful predictor. Cavernous sinus invasion remains the best predictor of incomplete resection. PMID- 26843025 TI - A mechanistic view of drying suspension droplets. AB - When a dispersion droplet dries, a rich variety of spatial and temporal heterogeneities emerge. Controlling these phenomena is essential for many applications yet requires a thorough understanding of the underlying mechanisms. Although the process of film formation from initially dispersed polymer particles is well documented and is known to involve three main stages - evaporation, particle deformation and coalescence - it is impossible to fully disentangle the effects of particle deformation and coalescence, as these stages are closely linked. We circumvent this problem by studying suspensions of colloidal rubber particles that are incapable of coalescing. Varying the crosslink density allows us to tune the particle deformability in a controlled manner. We develop a theoretical framework of the main regimes and stresses in drying droplets of these suspensions, and validate this framework experimentally. Specifically, we show that changing the particle modulus by less than an order of magnitude can completely alter the stress development and resulting instabilities. Scanning electron microscopy reveals that particle deformability is a key factor in stress mitigation. Our model is the suspension equivalent of the widely used Routh Russel model for film formation in drying dispersions, with additional focus on lateral nonuniformities such as cracking and wrinkling inherent to the droplet geometry, thus adding a new dimension to the conventional view of particle deformation. PMID- 26843024 TI - Ten-year outcomes of intensity-modulated radiation therapy combined with neoadjuvant hormonal therapy for intermediate- and high-risk patients with T1c T2N0M0 prostate cancer. AB - BACKGROUND: We aimed to analyze the 10-year outcomes of intensity-modulated radiation therapy (IMRT) combined with neoadjuvant hormonal therapy (HT) for patients with intermediate- and high-risk T1c-T2N0M0 prostate cancer. METHODS: Fifty patients with T1c-T2N0M0 prostate cancer, who were treated with high-dose IMRT combined with neoadjuvant HT, were evaluated. Of these patients, 19 and 31 were classified into the intermediate- and high-risk groups, respectively. Neoadjuvant HT was administered over a median duration of 6 months; 74 and 78 Gy in 2 Gy per fraction were essentially delivered to the intermediate- and high risk cases, respectively. Adjuvant HT was not administered to any of the patients after the completion of IMRT. RESULTS: Over a median follow-up period of 118 months, the 10-year prostate-specific antigen failure-free survival, prostate specific antigen failure-free, salvage hormonal therapy-free, prostate cancer specific survival, and overall survival rates were 70.2 %, 78.7 %, 89.2 %, 100 %, and 88.8 %, respectively. No grade 3 or higher acute or late toxicities were observed. The 10-year likelihoods of developing grade 2 late urinary and rectal toxicities were 13.7 % and 4.2 %, respectively. Compared with the outcomes of a cohort of historical controls who were locally irradiated with 70 Gy by three dimensional conformal radiotherapy, the prostate-specific antigen failure-free rate was significantly better in the IMRT groups (78.7 % vs. 53.4 % at 10 years; p = 0.027). CONCLUSIONS: High-dose IMRT combined with neoadjuvant HT achieved not only high prostate-specific antigen control, but also excellent survival outcomes with acceptable morbidities, for a Japanese cohort of intermediate- and high-risk T1c-T2N0M0 prostate cancer patients, and these results warrant further investigation. PMID- 26843026 TI - Natural history of 107 cases of fetal aortic stenosis from a European multicenter retrospective study. AB - OBJECTIVES: Fetal aortic valvuloplasty (FV) aims to prevent fetal aortic valve stenosis progressing into hypoplastic left heart syndrome (HLHS), which results in postnatal univentricular (UV) circulation. Despite increasing numbers of FVs performed worldwide, the natural history of the disease in fetal life remains poorly defined. The primary aim of this study was to describe the natural history of fetal aortic stenosis, and a secondary aim was to test previously published criteria designed to identify cases of emerging HLHS with the potential for a biventricular (BV) outcome after FV. METHODS: From a European multicenter retrospective study of 214 fetuses with aortic stenosis (2005-2012), 107 fetuses in ongoing pregnancies that did not undergo FV were included in this study and their natural history was reported. We examined longitudinal changes in Z-scores of aortic and mitral valve and left ventricular dimensions and documented direction of flow across the foramen ovale and aortic arch, and mitral valve inflow pattern and any gestational changes. Data were used to identify fetuses satisfying the Boston criteria for emerging HLHS and estimate the proportion of these that would have been ideal FV candidates. We applied the threshold score whereby a score of 1 was assigned to fetuses for each Z-score meeting the following criteria: left ventricular length and width > 0; mitral valve diameter > -2; aortic valve diameter > -3.5; and pressure gradient across either the mitral or aortic valve > 20 mmHg. We compared the predicted circulation with known survival and final postnatal circulation (BV, UV or conversion from BV to UV). RESULTS: Among the 107 ongoing pregnancies there were eight spontaneous fetal deaths and 99 livebirths. Five were lost to follow-up, five had comfort care and four had mild aortic stenosis not requiring intervention. There was intention-to-treat in these 85 newborns but five died prior to surgery, before circulation could be determined, and thus 80 underwent postnatal procedures with 44 BV, 29 UV and seven BV-to-UV circulatory outcomes. Of newborns with intention to-treat, 69/85 (81%) survived >= 30 days. Survival at median 6 years was superior in cases with BV circulation (P = 0.041). Those with a postnatal UV circulation showed a trend towards smaller aortic valve diameters at first scan than did the BV cohort (P = 0.076), but aortic valve growth velocities were similar in both cohorts to term. In contrast, the mitral valve diameter was significantly smaller at first scan in those with postnatal UV outcomes (P = 0.004) and its growth velocity (P = 0.008), in common with the left ventricular inlet length (P = 0.004) and width (P = 0.002), were reduced significantly by term in fetuses with UV compared with BV outcome. Fetal data, recorded before 30 completed gestational weeks, from 70 treated neonates were evaluated to identify emerging HLHS. Forty-four had moderate or severe left ventricular depression and 38 of these had retrograde flow in the aortic arch and two had left-to-right flow at atrial level and reversed a-waves in the pulmonary veins. Thus 40 neonates met the criteria for emerging HLHS and BV circulation was documented in 13 (33%). Of these 40 cases, 12 (30%) had a threshold score of 4 or 5, of which five (42%) had BV circulation without fetal intervention. CONCLUSIONS: The natural history in our cohort of fetuses with aortic stenosis and known outcomes shows that a substantial proportion of fetuses meeting the criteria for emerging HLHS, with or without favorable selection criteria for FV, had a sustained BV circulation without fetal intervention. This indicates that further work is needed to refine the selection criteria to offer appropriate therapy to fetuses with aortic stenosis. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26843027 TI - Engineered Tug-of-War Between Kinesin and Dynein Controls Direction of Microtubule Based Transport In Vivo. AB - Bidirectional transport of membrane organelles along microtubules (MTs) is driven by plus-end directed kinesins and minus-end directed dynein bound to the same cargo. Activities of opposing MT motors produce bidirectional movement of membrane organelles and cytoplasmic particles along MT transport tracks. Directionality of MT-based transport might be controlled by a protein complex that determines which motor type is active at any given moment of time, or determined by the outcome of a tug-of-war between MT motors dragging cargo organelles in opposite directions. However, evidence in support of each mechanisms of regulation is based mostly on the results of theoretical analyses or indirect experimental data. Here, we test whether the direction of movement of membrane organelles in vivo can be controlled by the tug-of-war between opposing MT motors alone, by attaching a large number of kinesin-1 motors to organelles transported by dynein to minus-ends of MTs. We find that recruitment of kinesin significantly reduces the length and velocity of minus-end-directed dynein dependent MT runs, leading to a reversal of the overall direction of dynein driven organelles in vivo. Therefore, in the absence of external regulators tug of-war between opposing MT motors alone is sufficient to determine the directionality of MT transport in vivo. PMID- 26843028 TI - The TOMPs ambient air monitoring network - Continuous data on UK air quality for over 20 years. AB - Long-term air monitoring datasets are needed for persistent organic pollutants (POPs) to assess the effectiveness of source abatement measures and the factors controlling ambient levels. The Toxic Organic Micro Pollutants (TOMPs) Network, which has operated since 1991, collects ambient air samples at six sites across England and Scotland, using high-volume active air samplers. The network provides long-term ambient air trend data for a range of POPs at both urban and rural locations. Data from the network provides the UK Government, regulators and researchers with valuable information on emission/source controls and on the effectiveness of international chemicals regulation such as the Stockholm Convention and UN/ECE Protocol on POPs. The target chemicals of TOMPs have been polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and, since 2010, polybrominated diphenyl ethers (PBDEs). The continuous monitoring of these compounds demonstrates the constant decline in UK air concentrations over the last two decades, with average clearance rates for PCDD/Fs in urban locations of 5.1 years and for PCBs across all sites 6.6 years. No significant declines in rural locations for PCDD/Fs have been observed. There is a strong observable link between the declining ambient air concentrations and the emission reductions estimated in the annually produced National Atmospheric Emission Inventory (NAEI) dataset. These findings clearly demonstrate the unique strengths of long-term consistent datasets for the evaluation of the success of chemical regulation and control. PMID- 26843029 TI - Time trends of persistent organic pollutants in spanish air. AB - Passive air samplers consisting of polyurethane foam (PUF) disks were deployed in seven remote points and four urban locations to assess levels of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), and some organochlorine pesticides including: 1,1'-(2,2,2-trichloroethane-1,1-diyl)bis(4-chlorobenzene) (DDT) and their metabolites (1,1-bis-(4-chlorophenyl)-2,2-dichloroethene (DDE) and 1-chloro 4-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene (DDD)), hexaclorobenzene (HCB) and hexachlorocyclohexanes (HCHs), in the Spanish ambient air. Results revealed HCB (49 pg m(-3); median) as the major pollutant, followed in decreasing order by HCHs (21 pg m(-3)), ?DDT/E/Ds (20 pg m(-3)), PCBs (20 pg m(-3)), PBDEs (3.3 pg m( 3)) and PCDD/Fs (0.04 pg m(-3)), when urban and remote locations are evaluated together. Urban areas presented statistically significant (p < 0.05, Mann-Whitney U test) higher levels for all families studied, except for HCB, compared to remote locations revealing anthropogenic activities as potential sources for these chemicals. On the contrary, HCB concentrations seem to reflect background levels. Interestingly, results reveal a decreasing trend for PCBs, PBDEs and DDTs levels in remote areas, while this behaviour is only statistically significant in the case of the former chemicals in urban locations. The present study is framed in the Spanish air monitoring plan and represents the first complete analysis related to POP presence in Spanish air coming from inner sites. PMID- 26843030 TI - Persistent left superior vena cava: Two case reports and a review from nephrologists' perspective. AB - Thoracic venous anomalies without congenital heart anomalies are present in minority of the population, but they are frequent enough to be encountered while placing hemodialysis catheters through the jugular or subclavian veins. Persistent left superior vena cava is the most commonly seen anomaly and it is rarely noticed before the observation of an unusual course of hemodialysis catheter or guidewire on chest X-ray. We present two patients with previously unspotted persistent left superior vena cava and uncomplicated hemodialysis catheter insertions through the internal jugular veins with good catheter functions. Review of the relevant literature from a nephrologists' perspective with technical aspects is provided. PMID- 26843031 TI - Prenatal prediction of neonatal death in single ventricle congenital heart disease. AB - OBJECTIVE: The objective of this study was to determine whether prenatal ultrasound findings and cord blood N-terminal pro-B-type natriuretic peptide (NT pro-BNP) and cardiac troponin T (cTnT) can predict neonatal mortality in single ventricle congenital heart disease. METHODS: The association between neonatal mortality and prenatal ultrasound findings/cord blood biomarkers was evaluated in neonates delivered with a diagnosis of single ventricle congenital heart disease. The presence of prenatal ultrasound findings suggesting systemic outflow obstruction (ascending aorta < 2.5 percentile) or ventricular dysfunction (the presence of cardiomegaly or hydrops) was evaluated, and the total number of abnormal findings was converted to a numeric score called the 'single ventricle score'. In addition, NT pro-BNP and cTnT were measured in cord blood taken at the time of delivery. RESULTS: A total of 48 cases of single ventricle congenital heart disease were included. The rate of neonatal mortality was 31% (15/48). The presence of either abnormal ultrasound findings (single ventricle score >= 2) or elevated concentrations of NT pro-BNP or cTnT was associated with increased risk of neonatal death. CONCLUSION: The presence of either abnormal prenatal ultrasound findings or increased cord blood NT pro-BNP and cTnT concentrations was associated with the risk of neonatal death in single ventricle congenital heart disease. PMID- 26843033 TI - Synthesis and characterization of [(HPO3)6Mo21O60(H2O)4](8-): a new redox active heteropoly blue cluster with layered shape containing a phosphite template that self-assembles under controlled microwave irradiation. AB - The microwave-driven synthesis of a heteropoly blue cluster yields a redox active cluster, [(HPO3)6Mo21O60(H2O)4](8-), templated by six phosphite anions whereby two phosphites template a tri-lucunary {Mo15} Dawson structure, and one templates a {Mo6} ring with two of the three remaining phosphites acting as bridging ligands connecting the ring to the {Mo15}. PMID- 26843032 TI - Liver Fibrosis Can Be Induced by High Salt Intake through Excess Reactive Oxygen Species (ROS) Production. AB - High salt intake has been known to cause hypertension and other side effects. However, it is still unclear whether it also affects fibrosis in the mature or developing liver. This study demonstrates that high salt exposure in mice (4% NaCl in drinking water) and chick embryo (calculated final osmolality of the egg was 300 mosm/L) could lead to derangement of the hepatic cords and liver fibrosis using H&E, PAS, Masson, and Sirius red staining. Meanwhile, Desmin immunofluorescent staining of mouse and chick embryo livers indicated that hepatic stellate cells were activated after the high salt exposure. pHIS3 and BrdU immunohistological staining of mouse and chick embryo livers indicated that cell proliferation decreased; as well, TUNEL analyses indicated that cell apoptosis increased in the presence of high salt exposure. Next, dihydroethidium staining on the cultured chick hepatocytes indicated the excess ROS was generated following high salt exposure. Furthermore, AAPH (a known inducer of ROS production) treatment also induced the liver fibrosis in chick embryo. Positive Nrf2 and Keap1 immunohistological staining on mouse liver suggested that Nrf2/Keap1 signaling was involved in high salt induced ROS production. Finally, the CCK8 assay was used to determine whether or not the growth inhibitory effect induced by high salt exposure can be rescued by antioxidant vitamin C. Meanwhile, the RT-PCR result indicated that the Nrf2/Keap1 downsteam genes including HO-1, NQO-1, and SOD2 were involved in this process. In sum, these experiments suggest that high salt intake would lead to high risk of liver damage and fibrosis in both adults and developing embryos. The pathological mechanism may be the result from an imbalance between oxidative stress and the antioxidant system. PMID- 26843035 TI - Hybrid magnetoresistance in Pt-based multilayers: Effect originated from strong interfacial spin-orbit coupling. AB - The hybrid magnetoresistance (MR) behaviors in Pt/Co90Fe10/Pt, Mn1.5Ga/Pt and Mn1.5Ga/Pt/Co90Fe10/Pt multilayers have been investigated. Both planer Hall effect (PHE) and angle-dependent MR in Pt/Co90Fe10/Pt revealed the combination of spin Hall MR (SMR) and normal anisotropic MR (AMR), indicating the large contribution of strong spin-orbit coupling (SOC) at the interfaces. When Pt contacted with perpendicular magnetic anisotropy (PMA) metal Mn1.5Ga, the strong interfacial SOC modified the effective anomalous Hall effect. The MR in Mn1.5Ga/Pt/Co90Fe10/Pt is not a simple combination of SMR and AMR, but ascribed to the complicated domain wall scattering and strong interfacial SOC when Pt is sandwiched by the in-plane magnetized Co90Fe10 and the PMA Mn1.5Ga. PMID- 26843034 TI - The macrophage activation product sCD163 is associated with a less favourable metabolic profile in prepubertal children. AB - OBJECTIVE: Macrophages are known to be involved in low-grade inflammatory processes such as obesity. soluble cluster of differentiation 163 (sCD163) is shed from the cell surface as specific macrophage activation marker. In prepubertal children, we studied if circulating sCD163 is associated with metabolic and cardiovascular risk markers. METHODS: A population of 236 school aged Caucasian children (111 girls and 125 boys) aged 8 +/- 1 year [81 normal weight (body mass index [BMI]-SDS < 1); 74 overweight (1 <= BMI-standard deviation score [SDS] < 2) and 81 with obesity (BMI-SDS >= 2)] were studied. BMI, waist circumference, fat mass and visceral fat were measured. Fasting serum sCD163, homeostatic model assessment of insulin resistance, high sensitivity C reactive protein, gamma-glutamyl transpeptidase and lipids were quantified. RESULTS: Circulating sCD163 concentrations were higher in children with obesity (p < 0.0001). Associations were observed between circulating sCD163 and a less favourable metabolic profile as judged by higher waist circumference, fat mass, visceral fat, epicardial fat, homeostatic model assessment of insulin resistance, high sensitivity C-reactive protein, gamma-glutamyl transpeptidase and triglycerides (all between r = 0.173 and r = 0.363; p < 0.05 to p < 0.0001) and lower high-density lipoprotein-cholesterol (r = -0.285, p < 0.0001). In multiple regression analyses, circulating sCD163 was independently associated with HOMA-IR (beta = 0.162, p = 0.016; model R2 = 0.179) and high density lipoprotein cholesterol/triglycerides ratio (beta = -0.167, p = 0.012; model R2 = 0.209). CONCLUSIONS: Childhood obesity may increase the risk of developing metabolic diseases later in life through chronic macrophage activation having deleterious effects on metabolism. PMID- 26843036 TI - Effect of Acupuncture on the Motor and Nonmotor Symptoms in Parkinson's Disease- A Review of Clinical Studies. AB - Parkinson's disease is a neurodegenerative disorder. Parkinson's clinical feature is characterized by its motor manifestations, although its many nonmotor symptoms occur earlier and have more profound impact on the quality of patient's life. Acupuncture has been increasingly popular and has been used to treat patients with Parkinson's. In this article, we have studied the clinical reports of acupuncture treatment for Parkinson's, which were listed in Medline, PubMed, EMBASE, CNKI, and CINAHL databases in the past 15 years. It was found that acupuncture either manual or electroacupuncture stimulation at specific acupoints relieved some motor symptoms in patients with Parkinson's and markedly improved many nonmotor symptoms such as psychiatric disorders, sleep problems, and gastrointestinal symptoms. When it was used as an adjunct for levodopa, acupuncture improved therapeutic efficacy and reduced dosage and the occurrence of side effects of levodopa. However, the results were constrained by small sample sizes, methodological flaws, and blinding methods of studies. Although the evidence for the effectiveness of acupuncture for treating Parkinson's is inconclusive, therapeutic potential of acupuncture seems quite promising. More studies, either comparative effectiveness research or high-quality placebo controlled clinical studies are warranted. PMID- 26843037 TI - Preparation and Characterization of Immobilized Lipase from Pseudomonas Cepacia onto Magnetic Cellulose Nanocrystals. AB - Magnetic cellulose nanocrystals (MCNCs) were prepared and used as an enzyme support for immobilization of Pseudomonas cepacialipase (PCL). PCL was successfully immobilized onto MCNCs (PCL@MCNC) by a precipitation-cross-linking method. The resulting PCL@MCNC with a nanoscale size had high enzyme loading (82.2 mg enzyme/g) and activity recovery (95.9%). Compared with free PCL, PCL@MCNC exhibited significantly enhanced stability and solvent tolerance, due to the increase of enzyme structure rigidity. The observable optimum pH and temperature for PCL@MCNC were higher than those of free PCL. PCL@MCNC manifested relatively higher enzyme-substrate affinity and catalytic efficiency. Moreover, PCL@MCNC was capable of effectively catalyzing asymmetric hydrolysis of ketoprofenethyl ester with high yield of 43.4% and product e.e. of 83.5%. Besides, immobilization allowed PCL@MCNC reuse for at least 6 consecutive cycles retaining over 66% of its initial activity. PCL@MCNC was readily recycled by magnetic forces. Remarkably, the as-prepared nanobiocatalyst PCL@MCNC is promising for biocatalysis. PMID- 26843039 TI - Corrigendum on: Ertem K, Karakoc Y and Pepele D. The absence of palmaris longus tendon andits contribution to pinch strength in the Anatolian population. J Hand Surg Eur. 2011, 36, 6: 517-8. PMID- 26843040 TI - Morning meetings and ward rounds must be retained as the essential components of clinical service. PMID- 26843038 TI - Twenty-four-hour pattern of intra-ocular pressure in untreated patients with primary open-angle glaucoma. AB - PURPOSE: To investigate and compare the 24-hr intra-ocular pressure (IOP) pattern among different severities of glaucomatous optic neuropathy (GON) together with different subtypes of primary open-angle glaucoma (POAG). METHODS: The IOPs of untreated patients with POAG were measured every 2 hrs over a 24-hr period. Subjects were divided into mild, moderate and severe groups according to the glaucoma staging system 2. The two POAG subtypes, normal tension glaucoma (NTG) and hypertension glaucoma (HTG) were classified according to peak IOP values throughout the 24-hr period. The 24-hr IOP curves were obtained based on the average IOP value at each time-point. The mean, peak, trough and fluctuation of IOP together with the diurnal-to-nocturnal IOP change were calculated and compared among different groups. RESULTS: A total of 160 POAG patients (84 NTG and 76 HTG) were enrolled in the study. Generally, IOP decreased in the diurnal period and increased progressively during the nocturnal period, with peak IOP occurring from 2:00 AM to 10:00 AM. The average IOP values at all time-points were significantly higher in the mild group compared to the moderate and severe groups (p < 0.05). Compared with the NTG subjects, the IOP parameters including mean, peak, trough and fluctuation were significantly higher in the HTG subjects (p < 0.001), and IOP increased more predominantly in the HTG subtype during the nocturnal period. CONCLUSIONS: There was some regularity in the 24-hr IOP pattern in POAG, but different severities of GON and different subtypes might present different characteristics. Other non-IOP factors may lead to pathological IOP fluctuation and could be correlated with GON. PMID- 26843041 TI - A Targeted Q-PCR-Based Method for Point Mutation Testing by Analyzing Circulating DNA for Cancer Management Care. AB - Circulating cell-free DNA (cfDNA) is a valuable source of tumor material available with a simple blood sampling enabling a noninvasive quantitative and qualitative analysis of the tumor genome. cfDNA is released by tumor cells and exhibits the genetic and epigenetic alterations of the tumor of origin. Circulating cell-free DNA (cfDNA) analysis constitutes a hopeful approach to provide a noninvasive tumor molecular test for cancer patients. Based upon basic research on the origin and structure of cfDNA, new information on circulating cell-free DNA (cfDNA) structure, and specific determination of cfDNA fragmentation and size, we revisited Q-PCR-based method and recently developed a the allele-specific-Q-PCR-based method with blocker (termed as Intplex) which is the first multiplexed test for cfDNA. This technique, named Intplex((r)) and based on a refined Q-PCR method, derived from critical observations made on the specific structure and size of cfDNA. It enables the simultaneous determination of five parameters: the cfDNA total concentration, the presence of a previously known point mutation, the mutant (tumor) cfDNA concentration (ctDNA), the proportion of mutant cfDNA, and the cfDNA fragmentation index. Intplex((r)) has enabled the first clinical validation of ctDNA analysis in oncology by detecting KRAS and BRAF point mutations in mCRC patients and has demonstrated that a blood test could replace tumor section analysis for the detection of KRAS and BRAF mutations. The Intplex((r)) test can be adapted to all mutations, genes, or cancers and enables rapid, highly sensitive, cost-effective, and repetitive analysis. As regards to the determination of mutations on cfDNA Intplex((r)) is limited to the mutational status of known hotspot mutation; it is a "targeted approach." However, it offers the opportunity in detecting quantitatively and dynamically mutation and could constitute a noninvasive attractive tool potentially allowing diagnosis, prognosis, theranostics, therapeutic monitoring, and follow-up of cancer patients expanding the scope of personalized cancer medicine. PMID- 26843042 TI - COLD-PCR: Applications and Advantages. AB - Co-amplification at lower denaturation temperature-based polymerase chain reaction (COLD-PCR) is a single-step amplification method that results in the enhancement of both known and unknown minority alleles during PCR, irrespective of mutation type and position. This method is based on exploitation of the critical temperature, Tc, at which mutation-containing DNA is preferentially melted over wild type. COLD-PCR can be a good strategy for mutation detection in specimens with high nonneoplastic cell content, small specimens in which neoplastic cells are difficult to micro-dissect and therefore enrich, and whenever a mutation is suspected to be present but is undetectable using conventional PCR and sequencing methods. We describe in this chapter our COLD-PCR based pyrosequencing method for KRAS mutation detection in various clinical samples using DNA extracted from either fresh or fixed paraffin-embedded tissue specimens. PMID- 26843043 TI - PCR-Based Detection of DNA Copy Number Variation. AB - Copy number variations are important polymorphisms that can influence gene expression within and close to the rearranged region, and results in phenotypic variation. Techniques that detect abnormalities in DNA copy number are therefore useful for studying the associations between DNA aberrations and disease phenotype and for locating critical genes. PCR-based detection of copy number of target gene using TaqMan copy number assay offers a reliable method to measure copy number variation in human genome. PMID- 26843044 TI - Emulsion PCR: Techniques and Applications. AB - Emulsion PCR (EmPCR) is a commonly employed method for template amplification in multiple NGS-based sequencing platforms. The basic principle of emPCR is dilution and compartmentalization of template molecules in water droplets in a water-in oil emulsion. Ideally, the dilution is to a degree where each droplet contains a single template molecule and functions as a micro-PCR reactor. Here, we discuss the basic principles, advantages, and challenges of applications of emPCR in clinical testing. We describe the methods of preparation and enrichment of template-positive Ion PGMTM Template OT2 200 Ion SphereTM Particles (ISPs) on the Ion Personal Genome Machine((r)) (PGMTM) System. For routine clinical testing, following library generation, we employ the automated Ion OneTouchTM System that includes the Ion OneTouchTM 2 and the Ion OneTouchTM ES instruments for template generation and enrichment of template-positive ISPs, respectively. PMID- 26843045 TI - Digital PCR: Principles and Applications. AB - Digital PCR is a robust PCR technique that enables precise and accurate absolute quantitation of target molecules by diluting and partitioning of the samples into numerous compartments. Automated partitioning can be attained by creating "water in-oil" emulsion (emulsion-based digital PCR) or using a chip with microchannels (microfluidics-based digital PCR). We discuss the advantages and a wide variety of clinical applications of this technique. We describe the droplet digital RT PCR protocol published by Jennings et al. for identification and absolute quantitation of BCR-ABL1 transcripts. PMID- 26843046 TI - Quantitative PCR for Plasma Epstein-Barr Virus Loads in Cancer Diagnostics. AB - Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis and is associated with posttransplant lymphoproliferative disease (PTLD), Hodgkin's lymphoma, Burkitt's lymphoma, nasopharyngeal carcinoma, and HIV-related lymphomas. It infects nearly all humans and then persists for the life of the host in a small proportion of benign B lymphocytes. EBV reactivation, usually in the setting of immunosuppression, is the main risk factor for development of EBV associated malignancies. EBV reactivation can be detected in tissue specimens using EBV-encoded RNA (EBER) in situ hybridization (ISH), which is routinely used for diagnosis of PTLD and nasopharyngeal carcinoma. However, EBER ISH cannot be routinely used for screening asymptomatic or monitoring posttreatment outcome due to difficulty in obtaining tissue specimens for testing and the nonquantitative nature of the assay. Recent studies have shown that EBV genomic DNA can be detected in blood of patients with EBV-associated diseases, and that monitoring of EBV viral load in blood could be an effective method of distinguishing disease associated EBV reactivation from incidental EBV present in benign B lymphocytes, and could be used for diagnostic screening and monitoring of EBV-associated diseases. In this chapter we discuss a protocol for quantitative plasma EBV DNA analysis. PMID- 26843048 TI - Locked Nucleic Acid Probes (LNA) for Enhanced Detection of Low-Level, Clinically Significant Mutations. AB - The detection of clinically significant somatic mutations present at low level in a tissue sample represents a challenge in any laboratory. While several high sensitivity methods are described, the incorporation of these new techniques in a clinical lab may be difficult if the technology is not readily available or requires major changes in the workflow of the laboratory. Techniques that are robust and easily adapted to existing laboratory protocols are highly advantageous. In this chapter we describe the use of locked nucleic acid (LNA) probes to modify existing polymerase chain reaction (PCR)-based protocols which can then be sequenced by Sanger sequencing. LNA probes are used to enhance the sensitivity of Sanger sequencing to mutation frequencies below 1 %. The method is robust and is easily incorporated for assessment of any sample with low tumor content or low mutant allele burden. PMID- 26843047 TI - High-Resolution Melt Curve Analysis in Cancer Mutation Screen. AB - High-resolution melt (HRM) curve analysis is a PCR-based assay that identifies sequence alterations based on subtle variations in the melting curves of mutated versus wild-type DNA sequences. HRM analysis is a high-throughput, sensitive, and efficient alternative to Sanger sequencing and is used to assess for mutations in clinically important genes involved in cancer diagnosis. The technique involves PCR amplification of a target sequence in the presence of a fluorescent double stranded DNA (dsDNA) binding dye, melting of the fluorescent amplicons, and subsequent interpretation of melt curve profiles. PMID- 26843049 TI - Genotyping of Frequent Mutations in Solid Tumors by PCR-Based Single-Base Extension and MassARRAY Analysis. AB - Over the last decade, cancer genome sequencing has revealed in detail the genomic landscapes of an increasing number of common solid human tumors. This has greatly impacted the clinical care of cancer patients based on the fact that many of these tumors exhibit activating mutations in driver genes that are prone to target therapy, largely impacting cancer management strategies. Genomic heterogeneity of tumors is becoming an increasingly recognized phenomenon relevant to genome-based medicine. Because a large number tumors may display several mutations at the same time, multiplexing has become the preferred approach to reveal the mutational landscape in patient samples and to better design a targeted approach to their illness. PMID- 26843050 TI - Microfluidics-Based PCR for Fusion Transcript Detection. AB - The microfluidic technology allows the production of network of submillimeter size fluidic channels and reservoirs in a variety of material systems. The microfluidic-based polymerase chain reaction (PCR) allows automated multiplexing of multiple samples and multiple assays simultaneously within a network of microfluidic channels and chambers that are co-ordinated in controlled fashion by the valves. The individual PCR reaction is performed in nanoliter volume, which allows testing on samples with limited DNA and RNA. The microfluidics devices are used in various types of PCR such as digital PCR and single molecular emulsion PCR for genotyping, gene expression, and miRNA expression. In this chapter, the use of a microfluidics-based PCR for simultaneous screening of 14 known fusion transcripts in patients with leukemia is described. PMID- 26843051 TI - Polymerase Chain Reaction Diagnosis of Leishmaniasis: A Species-Specific Approach. AB - Leishmaniasis is an infectious disease caused by protozoan parasites of the genus Leishmania which are transmitted to humans through bites of infected sand flies. The variable clinical manifestations and the evolution of the disease are determined by the infecting species. Recognition at a species level is of utmost importance since this greatly impacts therapy decision making as well as predicts outcome for the disease. This chapter describes the application of polymerase chain reaction (PCR) in the detection of Leishmania parasites across the disease spectrum, including protocols for sample collection and transportation, genomic material extraction, and target amplification methods with special emphasis on PCR amplification of the cytochrome b gene for Leishmania spp. species identification. PMID- 26843052 TI - Detection of Trypanosoma cruzi by Polymerase Chain Reaction. AB - American Trypanosomiasis (Chagas disease) is an infectious disease caused by the hemoflagellate parasite Trypanosoma cruzi which is transmitted by reduviid bugs. T. cruzi infection occurs in a broad spectrum of reservoir animals throughout North, Central, and South America and usually evolves into an asymptomatic chronic clinical stage of the disease in which diagnosis is often challenging. This chapter describes the application of polymerase chain reaction (PCR) for the detection of Trypanosoma cruzi DNA including protocols for sample preparation, DNA extraction, and target amplification methods. PMID- 26843053 TI - PCR Techniques in Next-Generation Sequencing. AB - With the advent of next-generation sequencing and its prolific use in the clinical realm, it would appear that techniques such as PCR would not be in high demand. This is not the case however, as PCR techniques play an important role in the success of NGS technology. Although NGS has rapidly become an important part of clinical molecular diagnostics, whole genome sequencing is still difficult to implement in a clinical laboratory due to high costs of sequencing, as well as issues surrounding data processing, analysis, and data storage, which can reduce efficiency and increase turnaround times. As a result, targeted sequencing is often used in clinical diagnostics, due to its increased efficiency. PCR techniques play an integral role in targeted NGS sequencing, allowing for the generation of multiple NGS libraries and the sequencing of multiple targeted regions simultaneously. We will outline the methods we employ in PCR amplification of targeted genomic regions for cancer mutation hotspots using the Ampliseq Cancer Hotspot v2 panel (Life Technologies, Carlsbad, CA). PMID- 26843054 TI - Single-Cell Quantitative PCR: Advances and Potential in Cancer Diagnostics. AB - Tissues are heterogeneous in their components. If cells of interest are a minor population of collected tissue, it would be difficult to obtain genetic or genomic information of the interested cell population with conventional genomic DNA extraction from the collected tissue. Single-cell DNA analysis is important in the analysis of genetics of cell clonality, genetic anticipation, and single cell DNA polymorphisms. Single-cell PCR using Single Cell Ampligrid/GeXP platform is described in this chapter. PMID- 26843055 TI - Quantitative Real-Time PCR: Recent Advances. AB - Quantitative real-time polymerase chain reaction is a technique for simultaneous amplification and product quantification of a target DNA as the process takes place in real time in a "closed-tube" system. Although this technique can provide an absolute quantification of the initial template copy number, quantification relative to a control sample or second sequence is typically adequate. The quantification process employs melting curve analysis and/or fluorescent detection systems and can provide amplification and genotyping in a relatively short time. Here we describe the properties and uses of various fluorescent detection systems used for quantification. PMID- 26843056 TI - PCR Techniques in Characterizing DNA Methylation. AB - DNA methylation was the first epigenetic mark to be discovered, involving the addition of a methyl group to the 5' position of cytosine by DNA methyltransferases, and can be inherited through cell division. DNA methylation plays an important role in normal human development and is associated with the regulation of gene expression, tumorigenesis, and other genetic and epigenetic diseases. Differential methylation is now known to play a central role in the development and outcome of most if not all human malignancies.Bisulfite conversion is a commonly used approach for gene-specific DNA methylation analysis. Treatment of DNA with bisulfite converts cytosine to uracil while leaving 5-methylcytosine intact, allowing for single-nucleotide resolution information about the methylated areas of DNA. PCR-based methods are routinely used to study DNA methylation on a gene-specific basis, after bisulfite treatment. Variations of this method include bisulfite sequencing, methylation specific PCR, real-time PCR-based MethyLight, and methylation-sensitive high resolution melting PCR. Several whole-epigenome profiling technologies such as MethylC-seq reduced representation bisulfite sequencing (RRBS) and the Infinium Human methylation 450 K bead chip are now available allowing for the identification of epigenetic drivers of disease processes as well as biomarkers that could potentially be integrated into clinical practice. PMID- 26843057 TI - Characteristics of second breast events among women treated with breast conserving surgery for DCIS in the community. AB - We examined the clinical/pathologic features of ipsilateral second breast cancers (IP-SBCs) following breast-conserving surgery (BCS) for DCIS among community treated patients and ascertained the degree of correlation between the features of index DCIS and IP-SBC events. From a Cancer Research Network cohort of DCIS patients diagnosed 1990-2001 and treated with BCS, we identified women who subsequently developed an ipsilateral DCIS or invasive breast cancer. All index DCIS tumors underwent expert pathology review. Pathologic characteristics of IP SBCs were abstracted from available medical records. Logistic regression was used to examine associations between pathologic characteristics and identify factors associated with invasive versus non-invasive IP-SBC. Of 1969 DCIS patients, 182 developed an IP-SBC within a median of 38 months (range 6-160). IP-SBCs were slightly more commonly non-invasive (53 %) versus invasive (47 %). Of invasive IP SBCs, 31 % were high grade, 67 % were <20 mm, 74 % were estrogen receptor positive, 7 % were HER2 positive, and 16 % were node positive. Of non-invasive IP SBCs, 33 % were high grade. Comparing index DCIS and IP-SBC specimens, there was moderate-high correlation for HR status and grade. Among patients with IP-SBCs, those who were younger and whose index DCIS tumors were HR negative had shorter intervals (within 3 years) between index and IP-SBC diagnoses. No index DCIS feature was statistically significantly associated with an IP-SBC that was invasive versus non-invasive. Understanding the characteristics of SBCs and identifying correlations between these and index DCIS events could influence treatment choices for DCIS, and may help patients and providers develop treatment paradigms for SBCs. PMID- 26843058 TI - Increased expression of senescence markers p14(ARF) and p16(INK4a) in breast cancer is associated with an increased risk of disease recurrence and poor survival outcome. AB - AIMS: Breast cancer is a hormonally driven disease. Cellular senescence is an age related irreversible cell cycle arrest at the G1 phase upon induction. The aim of this study was to characterize the expression patterns of the senescence markers p14(ARF) , p16(INK4a) and p21(WAF1/Cip1) during breast cancer progression in a large patient cohort. METHODS AND RESULTS: We conducted a retrospective study of 1080 patients with invasive ductal carcinoma, no special type, over an 11-year period. We performed immunohistochemical staining on tissue microarrays that included normal, benign hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma tissue from each patient. Invasive ductal carcinomas showed higher expression of p14(ARF) and p16(INK4a) but lower expression of p21(WAF1/Cip1) than non-malignant tissues. There were significant correlations of normal, benign, preinvasive and malignant tissues with p14(ARF) , p16(INK4a) and p21(WAF1/Cip1) expression (P < 0.05). Univariate comparison showed a correlation between high p16(INK4a) expression and poor survival (P = 0.000) and an increased risk of relapse (P = 0.000), whereas high p14(ARF) expression correlated only with an increased risk of relapse (P = 0.038). Multivariate analysis showed p16(INK4a) to be an important prognostic factor for overall survival (P = 0.011) and disease free survival (P = 0.004), with p14(ARF) also being a significant prognostic factor for disease-free survival (P = 0.043). Moreover, patients showing both high p16(INK4a) expression and and high p14(ARF) expression had an adjusted three fold increased risk of disease recurrence (P < 0.05) and a two-fold increased risk of all-cause-related death (P < 0.05). CONCLUSIONS: These finding suggest p16(INK4a) expression and p14(ARF) expression may play an important role in the progression of proliferative breast tissue to invasive cancer, and may be useful as prognostic factors. PMID- 26843059 TI - Robotic hepatectomy: initial experience of a single institution in Singapore. AB - INTRODUCTION: In this study, we report our initial experience with robotic hepatectomy. METHODS: Consecutive patients who underwent robotic hepatectomy at Singapore General Hospital, Singapore, from February 2013 to February 2015 were enrolled in this study. The difficulty level of operations was graded using a novel scoring system for laparoscopic hepatectomies. RESULTS: During the two-year period, five consecutive robotic hepatectomies were performed (one left lateral sectionectomy, one non-anatomical segment II/III resection, one anatomical segment V resection with cholecystectomy, one extended right posterior sectionectomy and one non-anatomical segment V/VI resection). Two hepatectomies were performed for suspected hepatocellular carcinoma, two for solitary liver metastases and one for a large symptomatic haemangioma. The median age of the patients was 53 (range 38-66) years and the median tumour size was 2.5 (range 2.1 7.3) cm. The median total operation time was 340 (range 155-825) minutes and the median volume of blood loss was 300 (range 50-1,200) mL. There were no open conversions and no mortalities or major morbidities (> Clavien-Dindo Grade II). The difficulty level of the operations was graded as low in one case (Score 2), intermediate in three cases (Score 5, 6 and 6) and high in one case (Score 10). There was one minor morbidity, where the patient experienced Grade A bile leakage, which resolved spontaneously. The median length of postoperative hospital stay was 5 (range 4-7) days. CONCLUSION: Our initial experience confirmed the feasibility and safety of robotic hepatectomy. PMID- 26843060 TI - A case series of complicated infective otitis media requiring surgery in adults. AB - INTRODUCTION: With the advent of antibiotics, complications of otitis media have become less common. It is crucial for physicians to recognise otitis media and treat its complications early. Herein, we present our institution's experience with patients who required emergency surgical intervention for complications of otitis media. METHODS: Data on patients who underwent emergency surgery for complications of otitis media from 2004 to 2011 was retrieved from the archives of the Department of Otolaryngology, Changi General Hospital, Singapore. RESULTS: A total of 12 patients (10 male, two female) underwent emergency surgery for complications of otitis media. The median age of the patients was 25 years. Otalgia, otorrhoea, headache and fever were the main presenting symptoms. Extracranial complications were observed in 11 patients, and six patients had associated intracranial complications. The primary otologic disease was acute otitis media in six patients, chronic otitis media without cholesteatoma in three patients and chronic otitis media with cholesteatoma in three patients. Mastoidectomy and drainage of abscess through the mastoid, with insertion of grommet tube, was the main surgical approach. Two patients required craniotomy. The mean length of hospital stay was 16.2 days and the mean follow-up period was 16.3 months. Five patients had residual conductive hearing loss; two patients with facial palsy had full recovery. CONCLUSION: Otitis media can still result in serious complications in the post-antibiotic era. Patients with otitis media should be monitored, and prompt surgical intervention should be performed when necessary to attain good outcomes. PMID- 26843061 TI - Post-marketing withdrawal of 462 medicinal products because of adverse drug reactions: a systematic review of the world literature. AB - BACKGROUND: There have been no studies of the patterns of post-marketing withdrawals of medicinal products to which adverse reactions have been attributed. We identified medicinal products that were withdrawn because of adverse drug reactions, examined the evidence to support such withdrawals, and explored the pattern of withdrawals across countries. METHODS: We searched PubMed, Google Scholar, the WHO's database of drugs, the websites of drug regulatory authorities, and textbooks. We included medicinal products withdrawn between 1950 and 2014 and assessed the levels of evidence used in making withdrawal decisions using the criteria of the Oxford Centre for Evidence Based Medicine. RESULTS: We identified 462 medicinal products that were withdrawn from the market between 1953 and 2013, the most common reason being hepatotoxicity. The supporting evidence in 72 % of cases consisted of anecdotal reports. Only 43 (9.34 %) drugs were withdrawn worldwide and 179 (39 %) were withdrawn in one country only. Withdrawal was significantly less likely in Africa than in other continents (Europe, the Americas, Asia, and Australasia and Oceania). The median interval between the first reported adverse reaction and the year of first withdrawal was 6 years (IQR, 1-15) and the interval did not consistently shorten over time. CONCLUSION: There are discrepancies in the patterns of withdrawal of medicinal products from the market when adverse reactions are suspected, and withdrawals are inconsistent across countries. Greater co-ordination among drug regulatory authorities and increased transparency in reporting suspected adverse drug reactions would help improve current decision-making processes. PMID- 26843062 TI - "Hit-and-Run" transcription: de novo transcription initiated by a transient bZIP1 "hit" persists after the "run". AB - BACKGROUND: Dynamic transcriptional regulation is critical for an organism's response to environmental signals and yet remains elusive to capture. Such transcriptional regulation is mediated by master transcription factors (TF) that control large gene regulatory networks. Recently, we described a dynamic mode of TF regulation named "hit-and-run". This model proposes that master TF can interact transiently with a set of targets, but the transcription of these transient targets continues after the TF dissociation from the target promoter. However, experimental evidence validating active transcription of the transient TF-targets is still lacking. RESULTS: Here, we show that active transcription continues after transient TF-target interactions by tracking de novo synthesis of RNAs made in response to TF nuclear import. To do this, we introduced an affinity labeled 4-thiouracil (4tU) nucleobase to specifically isolate newly synthesized transcripts following conditional TF nuclear import. Thus, we extended the TARGET system (Transient Assay Reporting Genome-wide Effects of Transcription factors) to include 4tU-labeling and named this new technology TARGET-tU. Our proof-of principle example is the master TF Basic Leucine Zipper 1 (bZIP1), a central integrator of metabolic signaling in plants. Using TARGET-tU, we captured newly synthesized mRNAs made in response to bZIP1 nuclear import at a time when bZIP1 is no longer detectably bound to its target. Thus, the analysis of de novo transcripomics demonstrates that bZIP1 may act as a catalyst TF to initiate a transcriptional complex ("hit"), after which active transcription by RNA polymerase continues without the TF being bound to the gene promoter ("run"). CONCLUSION: Our findings provide experimental proof for active transcription of transient TF-targets supporting a "hit-and-run" mode of action. This dynamic regulatory model allows a master TF to catalytically propagate rapid and broad transcriptional responses to changes in environment. Thus, the functional read out of de novo transcripts produced by transient TF-target interactions allowed us to capture new models for genome-wide transcriptional control. PMID- 26843063 TI - Suppression of the antiferromagnetic pseudogap in the electron-doped high temperature superconductor by protect annealing. AB - In the hole-doped cuprates, a small number of carriers suppresses antiferromagnetism and induces superconductivity. In the electron-doped cuprates, on the other hand, superconductivity appears only in a narrow window of high doped Ce concentration after reduction annealing, and strong antiferromagnetic correlation persists in the superconducting phase. Recently, Pr(1.3 x)La0.7Ce(x)CuO4 (PLCCO) bulk single crystals annealed by a protect annealing method showed a high critical temperature of around 27 K for small Ce content down to 0.05. Here, by angle-resolved photoemission spectroscopy measurements of PLCCO crystals, we observed a sharp quasi-particle peak on the entire Fermi surface without signature of an antiferromagnetic pseudogap unlike all the previous work, indicating a dramatic reduction of antiferromagnetic correlation length and/or of magnetic moments. The superconducting state was found to extend over a wide electron concentration range. The present results fundamentally challenge the long-standing picture on the electronic structure in the electron doped regime. PMID- 26843064 TI - Equilibria Between Cell Membranes and Electrolyte Solution: Effect of Fatal Accidental Hypothermia. AB - Equilibria between the membranes of erythrocytes as well as thrombocytes and solution ions in fatal accidental hypothermia were analyzed using a theoretical four-equilibria model. The model was developed to determinate parameters characterizing cell membrane-surrounding ion interactions: the total surface concentrations of both acidic and basic groups C A, C B, and association constants K AH, K BOH. Knowledge of these parameters was necessary to calculate the theoretical values of surface charge density. The model was validated by curve-fitting the experimental data points to simulated data generated by the model. The experimental and theoretical surface charge density values agree at pH 2-8, at higher pH the deviation was observed. PMID- 26843065 TI - The Location of the Protonated and Unprotonated Forms of Arbidol in the Membrane: A Molecular Dynamics Study. AB - Arbidol is a potent broad-spectrum antiviral molecule for the treatment and prophylaxis of many viral infections. Viruses that can be inhibited by arbidol include enveloped and non-enveloped viruses, RNA and DNA viruses, as well as pH independent and pH-dependent ones. These differences in viral types highlight the broad spectrum of Arb antiviral activity and, therefore, it must affect a common viral critical step. Arbidol incorporates rapidly into biological membranes, and some of its antiviral effects might be related to its capacity to interact with and locate into the membrane. However, no information is available of the molecular basis of its antiviral mechanism/s. We have aimed to locate the protonated (Arp) and unprotonated (Arb) forms of arbidol in a model membrane system. Both Arb and Arp locate in between the hydrocarbon acyl chains of the phospholipids but its specific location and molecular interactions differ from each other. Whereas both Arb and Arp average location in the membrane palisade is a similar one, Arb tends to be perpendicular to the membrane surface, whereas Arp tends to be parallel to it. Furthermore, Arp, in contrast to Arb, seems to interact stronger with POPG than with POPC, implying the existence of a specific interaction between Arp, the protonated from, with negatively charged phospholipids. This data would suggest that the active molecule of arbidol in the membrane is the protonated one, i.e., the positively charged molecule. The broad antiviral activity of arbidol would be defined by the perturbation it exerts on membrane structure and therefore membrane functioning. PMID- 26843067 TI - Methotrexate intolerance in oral and subcutaneous administration in patients with juvenile idiopathic arthritis: a cross-sectional, observational study. AB - OBJECTIVES: Methotrexate (MTX) is the cornerstone disease-modifying anti rheumatic drug (DMARD) in juvenile idiopathic arthritis (JIA). In Dutch patients, MTX intolerance occurred frequently and was associated with subcutaneous (SC) administration. The aim of this study was to assess the prevalence of MTX intolerance and its association with the route of administration in a German cohort of JIA patients. METHODS: A cross-sectional study of JIA patients on MTX was performed. Primary outcome was MTX intolerance, which was determined using the validated Methotrexate Intolerance Severity Score (MISS) questionnaire. The prevalence of gastrointestinal adverse effects and MTX intolerance was compared between patients on MTX SC and MTX administered orally (PO). RESULTS: Of 179 JIA patients on MTX, 73 (40.8%) were intolerant. The odds of MTX intolerance were higher in patients using MTX exclusively SC compared to exclusively PO (adjusted odds ratio 3.37 [95% confidence interval 1.19-10.0]). There was strong evidence that the former experienced more behavioural complaints (76.1% vs. 47.4%, p=0.001) and weak evidence that they experienced more abdominal pain after MTX intake (43.5% vs. 27.4%, p=0.056). CONCLUSIONS: The prevalence of MTX intolerance was high and exclusively SC administration of MTX was associated with MTX intolerance and behavioural adverse effects. The prevalence of gastrointestinal adverse effects was at least as high as in patients on MTX PO. The frequently held assumption that SC causes fewer side effects than PO seems unwarranted. Definite answers about the differences between SC and PO administration with respect to safety and efficacy should be obtained by randomised trials. PMID- 26843066 TI - Graphene-Iodine Nanocomposites: Highly Potent Bacterial Inhibitors that are Bio compatible with Human Cells. AB - Graphene-composites, capable of inhibiting bacterial growth which is also bio compatible with human cells have been highly sought after. Here we report for the first time the preparation of new graphene-iodine nano-composites via electrostatic interactions between positively charged graphene derivatives and triiodide anions. The resulting composites were characterized by X-ray photoemission spectroscopy, UV-spectroscopy, Raman spectroscopy and Scanning electron microscopy. The antibacterial potential of these graphene-iodine composites against Klebsiella pneumonia, Pseudomonas aeruginosa, Proteus mirobilis, Staphylococcus aureus, and E. coli was investigated. In addition, the cytotoxicity of the nanocomposite with human cells [human white blood cells (WBC), HeLa, MDA-MB-231, Fibroblast (primary human keratinocyte) and Keratinocyte (immortalized fibroblast)], was assessed. DGO (Double-oxidizes graphene oxide) was prepared by the additional oxidation of GO (graphene oxide). This generates more oxygen containing functional groups that can readily trap more H(+), thus generating a positively charged surface area under highly acidic conditions. This step allowed bonding with a greater number of anionic triiodides and generated the most potent antibacterial agent among graphene-iodine and as-made povidone iodine (PVP-I) composites also exhibited nontoxic to human cells culture. Thus, these nano-composites can be used to inhibit the growth of various bacterial species. Importantly, they are also very low-cytotoxic to human cells culture. PMID- 26843069 TI - The Wuerzburg procedure: the tensor fasciae latae perforator is a reliable anatomical landmark to clearly identify the Hueter interval when using the minimally-invasive direct anterior approach to the hip joint. AB - BACKGROUND: The key for successful delivery in minimally-invasive hip replacement lies in the exact knowledge about the surgical anatomy. The minimally-invasive direct anterior approach to the hip joint makes it necessary to clearly identify the tensor fasciae latae muscle in order to enter the Hueter interval without damaging the lateral femoral cutaneous nerve. However, due to the inherently restricted overview in minimally-invasive surgery, this can be difficult even for experienced surgeons. METHODS AND SURGICAL TECHNIQUE: In this technical note, we demonstrate for the first time how to use the tensor fasciae latae perforator as anatomical landmark to reliably identify the tensor fasciae latae muscle in orthopaedic surgery. Such perforators are used for flaps in plastic surgery as they are constant and can be found at the lateral third of the tensor fasciae latae muscle in a direct line from the anterior superior iliac spine. CONCLUSION: As demonstrated in this article, a simple knowledge transfer between surgical disciplines can minimize the complication rate associated with minimally-invasive hip replacement. PMID- 26843068 TI - Viral load monitoring and antiretroviral treatment outcomes in a pediatric HIV cohort in Ghana. AB - BACKGROUND: HIV-infected children in sub-Saharan Africa may be at a high risk of staying on a failing first-line regimen and developing drug-resistance HIV variants due to lack of routine viral load monitoring. We investigated whether cumulative viral load, measured as viremia copy-years (VCY) could predict morbidity in a setting where viral load is not routinely monitored. METHODS: This was a single-center prospective observational longitudinal study of HIV-infected children initiating antiretroviral therapy (ART) at the Pediatric HIV/AIDS Care program at Korle-Bu Teaching Hospital in Accra, Ghana. The main outcome was morbidity measured as frequency of hospitalizations, opportunistic infections, and outpatient sick visits. The main explanatory variable was viral load measured as VCY. RESULTS: The study included 140 children who initiated ART between September 2009 and May 2013 and had at least 2 viral load measurements. There were 184 hospitalizations, with pneumonia being the most common cause (22.8 %). A total of 102 opportunistic infections was documented, with tuberculosis being the most common opportunistic infection (68 %). A total of 823 outpatient sick visits was documented, with upper respiratory infections (14.2 %) being the most common cause. Forty-four percent of our study participants had >4 log10 VCY. Children in this sub-cohort had a higher frequency of sick visits compared with those with <4 log10 VCY (p = 0.03). Only 6.5 % of children with >4 log10 VCY had been identified as treatment failure using WHO clinical and immunological treatment failure criteria. CONCLUSIONS: High level of cumulative viral load may translate to virological failure and subsequent increased all-cause morbidity. Our finding of potential utility of VCY in pediatrics warrants further investigations. VCY may be a good alternate to routine viral load measurement as its determination may be less frequent and could be personalized to save cost. PMID- 26843072 TI - The effects on coagulation of the reinfusion of unprocessed residual blood from the cardiopulmonary bypass. AB - BACKGROUND: Autologous blood transfusion is a common technique in cardiac surgery to directly re-infuse residual blood from the cardiopulmonary bypass (CPB) circuit to the patient. The objective of this study was to evaluate the effects of reinfusion of unprocessed residual pump blood on the coagulation system after separation from the CPB circuit and reversal of systemic heparin with protamine. MEASUREMENTS AND MAIN RESULTS: After ethics approval, 40 participants undergoing cardiac surgery were recruited in a prospective single center cohort study. Changes in coagulation were assessed with standard plasma based laboratory assays and thromboelastography. After the reinfusion of unprocessed residual pump blood there were decreases in the mean aPTT (effect size 6 s; SD: 6.05; p < 0.0001) and thrombin time (effect size 4.08 s; SD: 9.7; p = 0.01). There were no significant changes in PT, INR and D-dimer. Post reinfusion there were increases in fibrinogen, hemoglobin and platelet counts. There were improvements in the R-time (effect size 9.1 s; SD: 16.9; p = 0.0023), K-time (effect size 1.5 s; SD: 3.6 s; p = 0.0017), alpha angle (6.9 degrees ; SD: 15.8; p = 0.012), and maximum amplitude (3.0 mm; SD: 5.6, p = 0.002) on thromboelastography. CONCLUSION: The reinfusion of unprocessed residual CPB blood resulted in no deleterious effects on the coagulation system measured by both the common laboratory plasma based measurements of coagulation and thromboelastography. PMID- 26843071 TI - Effects of dopaminergic replacement therapy on motor speech disorders in Parkinson's disease: longitudinal follow-up study on previously untreated patients. AB - Although speech disorders represent an early and common manifestation of Parkinson's disease (PD), little is known about their progression and relationship to dopaminergic replacement therapy. The aim of the current study was to examine longitudinal motor speech changes after the initiation of pharmacotherapy in PD. Fifteen newly-diagnosed, untreated PD patients and ten healthy controls of comparable age were investigated. PD patients were tested before the introduction of antiparkinsonian therapy and then twice within the following 6 years. Quantitative acoustic analyses of seven key speech dimensions of hypokinetic dysarthria were performed. At baseline, PD patients showed significantly altered speech including imprecise consonants, monopitch, inappropriate silences, decreased quality of voice, slow alternating motion rates, imprecise vowels and monoloudness. At follow-up assessment, preservation or slight improvement of speech performance was objectively observed in two thirds of PD patients within the first 3-6 years of dopaminergic treatment, primarily associated with the improvement of stop consonant articulation. The extent of speech improvement correlated with L-dopa equivalent dose (r = 0.66, p = 0.008) as well as with reduction in principal motor manifestations based on the Unified Parkinson's Disease Rating Scale (r = -0.61, p = 0.02), particularly reflecting treatment-related changes in bradykinesia but not in rigidity, tremor, or axial motor manifestations. While speech disorders are frequently present in drug-naive PD patients, they tend to improve or remain relatively stable after the initiation of dopaminergic treatment and appear to be related to the dopaminergic responsiveness of bradykinesia. PMID- 26843073 TI - Frederick W. Alt received the 2015 Szent-Gyorgi Prize for Progress in Cancer Research. AB - The Szent-Gyorgyi Prize for Progress in Cancer Research is a prestigious scientific award established by the National Foundation for Cancer Research (NFCR)--a leading cancer research charitable organization in the United States that is committed to supporting scientific research and public education relating to the prevention, early diagnosis, better treatments, and ultimately, a cure for cancer. Each year, the Szent-Gyorgyi Prize honors an outstanding researcher, nominated by colleagues or peers, who has contributed outstanding, significant research to the fight against cancer, and whose accomplishments have helped improve treatment options for cancer patients. The Prize also promotes public awareness of the importance of basic cancer research and encourages the sustained investment needed to accelerate the translation of these research discoveries into new cancer treatments. This report highlights the pioneering work led by the 2015 Prize winner, Dr. Frederick Alt. Dr. Alt's work in the area of cancer genetics over four decades has helped to shape the very roots of modern cancer research. His work continues to profoundly impact the approaches that doctors around the globe use to diagnose and treat cancer. In particular, his seminal discoveries of gene amplification and his pioneering work on molecular mechanisms of DNA damage repair have helped to usher in the era of genetically targeted therapy and personalized medicine. PMID- 26843070 TI - Models of human core transcriptional regulatory circuitries. AB - A small set of core transcription factors (TFs) dominates control of the gene expression program in embryonic stem cells and other well-studied cellular models. These core TFs collectively regulate their own gene expression, thus forming an interconnected auto-regulatory loop that can be considered the core transcriptional regulatory circuitry (CRC) for that cell type. There is limited knowledge of core TFs, and thus models of core regulatory circuitry, for most cell types. We recently discovered that genes encoding known core TFs forming CRCs are driven by super-enhancers, which provides an opportunity to systematically predict CRCs in poorly studied cell types through super-enhancer mapping. Here, we use super-enhancer maps to generate CRC models for 75 human cell and tissue types. These core circuitry models should prove valuable for further investigating cell-type-specific transcriptional regulation in healthy and diseased cells. PMID- 26843074 TI - Aquisalinus flavus gen. nov., sp. nov., a member of the family Parvularculaceae isolated from a saline lake. AB - A Gram-stain-negative bacterium, strain D11M-2T, was isolated from a saline lake (Lake Dasugan) in Qaidam basin, Qinghai Province, China. Its taxonomic position was determined by using a polyphasic approach. Cells were non-spore-forming rods, 0.5-0.7 MUm wide and 1.2-1.6 MUm long, and motile by means of a single subpolar or lateral flagellum. Strain D11M-2T was strictly heterotrophic and aerobic, and catalase- and oxidase-positive. Growth was observed in the presence of 0-14.0% (w/v) NaCl (optimum, 2.0%), and at 10-35 degrees C (optimum, 30 degrees C) and pH 6.0-10.5 (optimum, pH 8.0). Strain D11M-2T contained Q-10 and Q-11 as the respiratory quinones and three unknown glycolipids as the major polar lipids. The major cellular fatty acids (>10.0%) were summed feature 8 (C18:1omega7c and/or C18:1omega6c) and C16:0. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain D11M-2T belonged to the family Parvularculaceae and formed a separate lineage that was independent of the two genera within the family Parvularculaceae. Strain D11M-2T exhibited 92.8-93.4% 16S rRNA gene sequence similarity to members of the genus Parvularcula (highest to Parvularcula bermudensis HTCC 2503T), and 90.2% to a member of the genus Amphiplicatus. The DNA G+C content was 59 mol% (Tm). Based on the phenotypic, chemotaxonomic and phylogenetic data, strain D11M-2T is considered to represent a novel species of a new genus in the family Parvularculaceae, for which the name Aquisalinus flavus gen. nov., sp. nov. is proposed. The type strain of Aquisalinus flavus is D11M-2T (=CGMCC 1.12921T=KCTC 42673T). PMID- 26843075 TI - The role of DNA methylation during anoxia tolerance in a freshwater turtle (Trachemys scripta elegans). AB - Oxygen deprivation is a lethal stress that only a few animals can tolerate for extended periods. This study focuses on analyzing the role of DNA methylation in aiding natural anoxia tolerance in a champion vertebrate anaerobe, the red-eared slider turtle (Trachemys scripta elegans). We examined the relative expression and total enzymatic activity of four DNA methyltransferases (DNMT1, DNMT2, DNMT3a and DNMT3b), two methyl-binding domain proteins (MBD1 and MBD2), and relative genomic levels of 5-methylcytosine under control, 5 h anoxic, and 20 h anoxic conditions in liver, heart, and white skeletal muscle (n = 4, p < 0.05). In liver, protein expression of DNMT1, DNMT2, MBD1, and MBD2 rose significantly by two- to fourfold after 5 h anoxic submergence compared to normoxic-control conditions. In heart, 5 h anoxia submergence resulted in a 1.4-fold increase in DNMT3a levels and a significant decrease in MBD1 and MBD2 levels to ~30 % of control values. In white muscle, DNMT3a and DNMT3b increased threefold and MBD1 levels increased by 50 % in response to 5 h anoxia. Total DNMT activity rose by 0.6-2.0-fold in liver and white muscle and likewise global 5mC levels significantly increased in liver and white muscle under 5 and 20 h anoxia. The results demonstrate an overall increase in DNA methylation, DNMT protein expression and enzymatic activity in response to 5 and 20 h anoxia in liver and white muscle indicating a potential downregulation of gene expression via this epigenetic mechanism during oxygen deprivation. PMID- 26843077 TI - Electrical atrial vulnerability and renal complications in type 2 diabetes. Reply to Montaigne D, Coisne A, Sosner P et al [letter]. PMID- 26843078 TI - The pancreas in humans with and without diabetes. PMID- 26843076 TI - Microbial transmission from mothers with obesity or diabetes to infants: an innovative opportunity to interrupt a vicious cycle. AB - Maternal obesity and diabetes dramatically increase the long-term risk for obesity in the next generation, and pregnancy and lactation may be critical periods at which to aim primary prevention to break the obesity cycle. It is becoming increasingly clear that the gut microbiome in newborns and infants plays a significant role in gut health and therefore child development. Alteration of the early infant gut microbiome has been correlated with the development of childhood obesity and autoimmune conditions, including asthma, allergies and, more recently, type 1 diabetes. This is likely to be due to complex interactions between mode of delivery, antibiotic use, maternal diet, components of breastfeeding and a network of regulatory events involving both the innate and adaptive immune systems within the infant host. Each of these factors are critical for informing microbiome development and can affect immune signalling, toxin release and metabolic signals, including short-chain fatty acids and bile acids, that regulate appetite, metabolism and inflammation. In several randomised controlled trials, probiotics have been administered with the aim of targeting the microbiome during pregnancy to improve maternal and infant health but the findings have often been confounded by mode of delivery, antibiotic use, ethnicity, infant sex, maternal health and length of exposure. Understanding how nutritional exposure, including breast milk, affects the assembly and development of both maternal and infant microbial communities may help to identify targeted interventions during pregnancy and in infants born to mothers with obesity or diabetes to slow the transmission of obesity risk to the next generation. The aim of this review is to discuss influences on infant microbiota colonisation and the mechanism(s) underlying how alterations due to maternal obesity and diabetes may lead to increased risk of childhood obesity. PMID- 26843079 TI - Potential Benefits of Prophylactic Cholecystectomy in Patients Undergoing Bariatric Bypass Surgery. PMID- 26843080 TI - Gastric Band Removal in Revisional Bariatric Surgery, One-Step Versus Two-Step: a Systematic Review and Meta-analysis. AB - We aimed to systematically review the literature comparing the safety of one-step versus two-step revisional bariatric surgery from laparoscopic adjustable gastric banding (LAGB) to Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). There is debate on the safety of removing the gastric band and performing revisional surgery immediately or in a delayed, two-step fashion due to potential higher complications in one-step revisions. A systematic and comprehensive search of the literature was conducted. Included studies directly compared one-step and two-step revisional surgery. Eleven studies were included with 1370 patients. Meta-analysis found comparable rates of complications, morbidity, and mortality between one-step and two-step revisions for both RYGB and SG groups. This suggests that immediate or delayed revisional bariatric surgeries are both safe options for LAGB revisions. PMID- 26843081 TI - The Use of Intraoperative Endoscopy Decreases Postoperative Stenosis in Laparoscopic Sleeve Gastrectomy. PMID- 26843082 TI - Effects of Bariatric Surgery on Serum Bile Acid Composition and Conjugation in a Diabetic Rat Model. AB - BACKGROUND: Serum bile acids (BAs) are elevated following bariatric surgery and have emerged as a potential glucose-lowering beneficial factor. The change of BA components and its underlying mechanisms may be of great significance during bariatric surgery. The aim of this study is to investigate the effects of different bariatric procedures on serum BA composition and explore the potential mechanisms using a diabetic rat model. METHODS: Duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham operation were performed in diabetic rats induced by high-fat diet (HFD) and streptozotocin (STZ). Body weight, food intake, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) were measured at indicated time points. Serum BAs composition and the expression of cholesterol 7alpha hydroxylase (CYP7A1), bile acid: CoA synthase (BACS) and bile acid-CoA: amino acid N-acyltransferase (BAAT) at both transcriptional and protein levels in the liver were evaluated at 12 weeks postoperatively. RESULTS: Compared with sham group, DJB and SG both achieved rapid and sustained improvements in glucose tolerance and insulin sensitivity. They also resulted in increased serum BAs, especially the taurine-conjugated BAs by elevated conjugation. No obvious difference was detected between DJB and SG except that SG achieved decreased weight gain and food intake. CONCLUSIONS: The preferentially elevated serum taurine-conjugated BAs were similar after different bariatric surgeries, and the enhanced conjugation of BAs in the liver might account for the changed serum BAs profiles. PMID- 26843083 TI - Preliminary Results of the Influence of Duodenojejunal Bypass in a Porcine Model of Streptozotocin-Induced Diabetes Mellitus. AB - BACKGROUND: Type 2 diabetic obese patients present with a normalization of plasma glucose levels shortly after most bariatric procedures, before any significant weight loss takes place. There is only scarce literature in the new field of metabolic surgery, with most experiments being performed on small animal models. AIM: Our aim is to develop a reliable large animal model for assessment of surgical correction of diabetes. METHOD: Titrated doses of streptozotocin (STZ) were used for induction of diabetes mellitus. After standardization of the surgical technique to avoid any restrictive component, three groups were created, a duodenojejunal bypass (DJB; n = 4), a gastroileal conduit (GIC; n = 3) near the ileocecal valve, and a sham (control; n = 5) group. Preoperative and postoperative glycemic curves were recorded by means of intravenous glucose tolerance tests. Body weight fluctuations were recorded as well. RESULTS: Diabetes was successfully induced with the use of STZ in all cases. Animals in the sham group remained diabetic for 3 weeks after operation. There was normalization of blood glucose levels in the operative groups during the 3-week postoperative follow-up, without significant body weight changes. The duodenojejunal group resulted in stronger positive response of glycemia. CONCLUSION: STZ-induced diabetes in swine leads to a reliable large animal model for assessment of metabolic surgical procedures. STZ is an effective but highly toxic means for inducing stable diabetes in the sensitive porcine model. Duodenojejunal bypass, although less invasive, seems to exert better antidiabetic effects than gastroileal conduit. PMID- 26843084 TI - Long-Term Effect of Gastric Bypass and Sleeve Gastrectomy on Severe Obesity: Do Preoperative Weight Loss and Binge Eating Behavior Predict the Outcome of Bariatric Surgery? AB - BACKGROUND: Few studies have examined weight loss sustainability after sleeve gastrectomy (SG). The purpose of this study was to determine long-term outcome after SG and gastric bypass (GBP) and learn whether preoperative weight loss and binge eating behavior can be used to predict outcome. MATERIALS AND METHODS: Together, 257 patients (64 % women) were operated, 163 by GBP and 94 by SG. Binge eating was assessed by binge eating scale (BES) and preoperative weight loss was advised to all, including very low-calorie diet for 5 weeks. Postoperative visits took place at 1 and 2 years, and long-term outcome was at median 5 years (range 2.29-6.85). Multivariate linear regression analysis was used to predict outcome at 2-year and long-term control. RESULTS: Median age was 48 years, weight 141.1 kg, and BMI 48.2 kg/m(2). Preoperative weight loss was median 4.9 % before GBP and 3.8 % before SG, P = 0.04. Total weight loss at year one was 24.1 % in GBP and 23.7 % in SG (P = 0.40), at year two 24.4 and 23.4 % (P = 0.26), and at long term control 23.0 and 20.2 % (P = 0.006), respectively. Weight was analyzed in 93, 88, and 89 % of those alive, respectively. BES did not predict weight outcome, but larger preoperative weight loss predicted less postoperative weight loss at 2 years. CONCLUSION: On long term, weight loss was better maintained after GBP compared with SG. Binge eating behavior was not a significant predictor, but larger preoperative weight loss predicted less postoperative weight loss for the next 2 years. PMID- 26843085 TI - Maintenance of Multivitamin Supplements After Sleeve Gastrectomy. AB - INTRODUCTION: After all bariatric procedures, multivitamin supplements are uniformly prescribed to minimize eventual deficiencies. These supplements are usually maintained long time, even during the whole life after malabsorptive techniques, while these are maintained at least during 1 year after restrictive procedures. Given that sleeve gastrectomy does not alter intestinal absorption, the supplements are possibly unnecessary, once the patient can take an adequate diet. PATIENTS AND METHODS: A prospective randomized study of patients undergoing a laparoscopic sleeve gastrectomy was performed. Patients were randomized into two groups: those patients receiving the multivitamin supplement (Multicentrum, Pfizer, 1 tablet/day) during 3 months (group 1) and those receiving the supplement during 12 months (group 2). Laboratory data were recorded: vitamins (D, B12 and folic acid) and oligoelements (calcium, iron, phosphorus, magnesium and zinc) at 3, 6 and 12 months after surgery. RESULTS: Eighty patients were included, 40 in each group. At 3 months, 7.5 % of the patients presented iron deficiency and 2.5 % ferritin one, similarly in both groups, that was corrected with specific extra iron supplements. At 6 months, one patient (2.5 %) in group 1 presented iron deficiency and one in group 2 vitamin D deficiency (NS). At 12 months, only one patient in group 2 presented vitamin D deficiency, treated with specific supplements. CONCLUSION: The maintenance of multivitamin supplements more than 3 months postoperatively seems to be of no benefit. It is preferable monitoring laboratory values and adding specific supplements when necessary. CLINICALTRIALS. GOV IDENTIFIER: NCT02620137. PMID- 26843086 TI - Pharmacokinetics, Pharmacodynamics, and Safety of MEDI4212, an Anti-IgE Monoclonal Antibody, in Subjects with Atopy: A Phase I Study. AB - INTRODUCTION: The anti-IgE therapy omalizumab is currently licensed for the treatment of moderate to severe allergic asthma and chronic idiopathic urticaria. Owing to limitations in the use of omalizumab, a need exists for optimized anti IgE therapies to broaden clinical indications and patient populations, and to improve dosing schedules. The objective of this phase I, randomized, placebo/omalizumab-controlled, first-in-human, dose-escalation study was to evaluate the pharmacokinetics, pharmacodynamics, and safety of the high-affinity, anti-IgE therapy MEDI4212 in non-Japanese and Japanese subjects with atopy and/or diagnostic IgE >= 30 IU/mL. METHODS: Subjects with atopy and/or baseline IgE >= 30 IU/mL were randomized to a single dose of subcutaneous (5, 15, 60, 150, or 300 mg) or intravenous (300 mg) MEDI4212, subcutaneous omalizumab, or placebo. Following administration, pharmacokinetic, pharmacodynamic [IgE (free and total), and cellular FcepsilonRI expression], and safety assessments were made. RESULTS: MEDI4212 rapidly suppressed free serum IgE to a greater extent than omalizumab; however, recovery of free IgE to baseline in MEDI4212-dosed subjects was rapid when compared with the slow and gradual recovery seen in omalizumab-dosed individuals. The loss of IgE suppression corresponded with a rapid decrease of serum MEDI4212. FcepsilonRI expression on dendritic cells and basophils was reduced following MEDI4212 dosing. MEDI4212 was well tolerated by subjects; adverse events were generally of low severity and no subjects discontinued due to adverse events. CONCLUSIONS: The increased potency of MEDI4212 may be of clinical interest for individuals with high-diagnostic IgE levels where more extensive IgE suppression is required for clinical response. However, the modest duration of free IgE suppression below the target concentration noted with MEDI4212 in this study suggests limited potential for dosing schedule advantages over omalizumab. FUNDING: MedImmune. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01544348. PMID- 26843088 TI - Photodynamic Therapy in Daylight for Actinic Keratoses. PMID- 26843087 TI - Association between alcohol consumption during pregnancy and risks of congenital heart defects in offspring: meta-analysis of epidemiological observational studies. AB - BACKGROUND: To explore the association between maternal alcohol consumption and/or binge drinking and congenital heart defects (CHDs), we conducted a meta analysis for more sufficient evidence on this issue. METHODS: We searched Medline, EMBASE, and the Cochrane Library from their inceptions to December 2014 for case-control and cohort studies that assessed the association between maternal alcohol consumption and CHD risk. Study-specific relative risk estimates were calculated using random-effect or fixed-effect models. RESULTS: A total of 19 case-control studies and 4 cohort studies were included in the meta-analysis. We observed a null association between maternal alcohol consumption during pregnancy and the risk of CHDs. Even in the analysis of different trimesters of pregnancy, we found little association between the two. CONCLUSIONS: This meta analysis suggests that maternal alcohol consumption is modestly not associated with the risk of CHDs. However, further investigation is needed to confirm this conclusion. PMID- 26843089 TI - Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury. AB - Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries. PMID- 26843090 TI - Prior exposure to a reverberant listening environment improves speech intelligibility in adult cochlear implant listeners. AB - OBJECTIVES: The goal of this study is to investigate whether prior exposure to reverberant listening environment improves speech intelligibility of adult cochlear implant (CI) users. METHODS: Six adult CI users participated in this study. Speech intelligibility was measured in five different simulated reverberant listening environments with two different speech corpuses. Within each listening environment, prior exposure was varied by either having the same environment across all trials (blocked presentation) or having different environment from trial to trial (unblocked). RESULTS: Speech intelligibility decreased as reverberation time increased. Although substantial individual variability was observed, all CI listeners showed an increase in the blocked presentation condition as compared to the unblocked presentation condition for both speech corpuses. CONCLUSION: Prior listening exposure to a reverberant listening environment improves speech intelligibility in adult CI listeners. Further research is required to understand the underlying mechanism of adaptation to listening environment. PMID- 26843091 TI - Demodex treatment in external ocular disease: the outcomes of a Tasmanian case series. AB - Demodex species (spp.) have previously been implicated in the pathogenesis of blepharitis. This study aims to correlate improvement in symptoms of external ocular disease with treatment of underlying Demodex spp. This is a prospective, observational case series of patients with chronic external ocular disease. Demodicosis was confirmed by microscopic examination of epilated eyelashes. The main outcome measure was response to the treatment (5 % tee tree oil) in regard to change in subjective symptoms utilising a symptom-based patient questionnaire assessment. Overall patients had a good response to the treatment in terms of improvement or resolution of symptoms, with 91 % of patients reporting at least some improvement in symptoms. The treatment of underlying Demodex spp. appears to result in improvement of symptoms in patients with long standing external ocular disease and underlying Demodex spp. infestation. PMID- 26843092 TI - Effects of a dietary intervention with conjugated linoleic acid on immunological and metabolic parameters in children and adolescents with allergic asthma--a placebo-controlled pilot trial. AB - BACKGROUND: Circumstantial evidence suggests that conjugated linoleic acid (CLA) beneficially modulates immune function in allergic subjects. C9,t11-CLA, naturally occurring in ruminant fats, is suggested to be the effective isomer. In contrast, for the t10,c12-CLA isomer, which is naturally found only in traces but usually constitutes a relevant part in commercial CLA mixtures, adverse effects have been reported. Aim of this study was to assess putative immunomodulatory effects of highly enriched c9,t11-CLA in allergic subjects. To our best knowledge, our study is the first in that a CLA preparation was used for such purpose which was free of t10,c12-CLA. DESIGN: Twenty-nine asthmatic children and adolescents (age 6-18 y) with diagnosed allergic sensitization against grass pollen, house dust mite, or cat hair/epithelia consumed daily a portion of yoghurt containing either 3 g CLA (75 % c9,t11-CLA, 87 % purity) or placebo (safflower oil) over a period of 12 weeks. At study start and end, lung function parameters, specific IgE, in vitro allergen-induced cytokine production in peripheral blood mononuclear cells (PBMC), plasma ECP, urinary 8-oxodG as marker of oxidation, fatty acid profiles of erythrocytes, and routine haematological parameters were determined. Prior to blood samplings, 3-days dietary records were requested. Throughout the study, the participants documented daily their peak expiratory flow and kept protocol about their allergy symptoms and usage of demand medication. RESULTS: In contrast to the CLA group, PBMC-produced IFN-gamma and IL-4 increased significantly and by trend, respectively, in the placebo group. Moreover, plasma ECP tended to increase in the placebo group. In the pollen subgroup, FEV1 improved upon both CLA and placebo oil supplementation. In both intervention groups, the n-6/n-3 PUFA ratio in red blood cells decreased, mainly due to an increase in n-3 PUFA. Moreover, 8-oxodG excretion increased in both groups. No changes occurred regarding specific IgE concentrations, allergy symptoms, and volume parameters. CONCLUSION: Our results indicate that CLA modestly dampens the inflammatory response on the cellular level. A clinically relevant amelioration of the symptoms could not be proved in atopic manifest patients. TRIAL REGISTRATION: NCT01026506. PMID- 26843093 TI - Acid-inducible proton influx currents in the plasma membrane of murine osteoclast like cells. AB - Acidification of the resorption pits, which is essential for dissolving bone, is produced by secretion of protons through vacuolar H(+)-ATPases in the plasma membrane of bone-resorbing cells, osteoclasts. Consequently, osteoclasts face highly acidic extracellular environments, where the pH gradient across the plasma membrane could generate a force driving protons into the cells. Proton influx mechanisms during the acid exposure are largely unknown, however. In this study, we investigated extracellular-acid-inducible proton influx currents in osteoclast like cells derived from a macrophage cell line (RAW264). Decreasing extracellular pH to <5.5 induced non-ohmic inward currents. The reversal potentials depended on the pH gradients across the membrane and were independent of concentrations of Na(+), Cl(-), and HCO3 (-), suggesting that they were carried largely by protons. The acid-inducible proton influx currents were not inhibited by amiloride, a widely used blocker for cation channels/transporters, or by 4,4'-diisothiocyanato 2,2'-stilbenesulfonate(DIDS) which blocks anion channels/transporters. Additionally, the currents were not significantly affected by V-ATPase inhibitors, bafilomycin A1 and N,N'-dicyclohexylcarbodiimide. Extracellular Ca(2+) (10 mM) did not affect the currents, but 1 mM ZnCl2 decreased the currents partially. The intracellular pH in the vicinity of the plasma membrane was dropped by the acid-inducible H(+) influx currents, which caused overshoot of the voltage-gated H(+) channels after removal of acids. The H(+) influx currents were smaller in undifferentiated, mononuclear RAW cells and were negligible in COS7 cells. These data suggest that the acid-inducible H(+) influx (H(+) leak) pathway may be an additional mechanism modifying the pH environments of osteoclasts upon exposure to strong acids. PMID- 26843094 TI - Lactate modulates the intracellular pH sensitivity of human TREK1 channels. AB - Tissue acidosis and high lactate concentrations are associated with cerebral ischaemia. The degree of acidosis is dependent on circulating glucose concentration, hyperglycaemia being associated with increased acidosis. Among other agents, lactate and protons have been shown to activate the leak potassium channel; TREK1 (TWIK related potassium channel 1) from the intracellular side and its increased activity is implicated in tolerance towards ischaemic cell damage. In the present study, we show that ischaemic concentrations of lactate (30 mM) at pH 7.0 and 6.5, commonly observed during ischemia, cause robust potentiation of human TREK1 (hTREK1) activity at single-channel level in cell-free inside-out membrane patches, while 30 mM lactate at pH 6.0 to 5.5, commonly observed during hyperglycaemic ischemia, reduces hTREK1 channel activity significantly. The biphasic effect of 30 mM lactate (ischaemic concentrations) on modulation of hTREK1 by varying pH conditions is specific since basal concentrations of lactate (3 mM) and 30 mM pyruvate at pH 7.0 and 5.5 failed to show similar effect as lactate. Experiments with deletion and point mutants of hTREK1 channel suggest that lactate changes the pH modulation of hTREK1 by interacting differently with the histidine residue at 328th position (H328) above and below its pKa (~6.0) in the intracellular carboxyl-terminal domain of TREK1. This lactate-induced pH modulation of hTREK1 is absent in C-terminal deletion mutant, CTDDelta100, and is similar in E321A-hTREK1 mutant as in wild-type hTREK1 suggesting that it is independent of pH-sensitive glutamate residue at 321st position. Such a differential pH-dependent effect of lactate on an ion channel function has not been reported earlier and has important implications in different stages of ischaemia. PMID- 26843095 TI - Endovascular stroke therapy in Austria: a nationwide 1-year experience. AB - BACKGROUND AND PURPOSE: Based on a tight network of stroke units (SUs) and interventional centres, endovascular treatment of acute major intracranial vessel occlusion has been widely implemented in Austria. Documentation of all patients in the nationwide SU registry has thereby become mandatory. METHODS: Demographic, clinical and interventional characteristics of patients who underwent endovascular treatment for acute ischaemic stroke in 11 Austrian interventional centres between 1 October 2013 and 30 September 2014 were analysed. RESULTS: In total, 301 patients (50.5% women; median age 70.5 years; median National Institutes of Health Stroke Scale score 17) were identified.193 patients (64.1%) additionally received intravenous thrombolysis. The most frequent vessel occlusion sites were the M1 segment of the middle cerebral artery (n = 161, 53.5%), the intracranial internal carotid artery (n = 60, 19.9%) and the basilar artery (n = 40, 13.3%). Stent retrievers were used in 235 patients (78.1%) and adequate reperfusion (modified Thrombolysis in Cerebral Infarction scores 2b and 3, median onset to reperfusion time 254 min) was achieved in 242 patients (81.4%). Symptomatic intracranial haemorrhage occurred in 7%. 43.8% of patients (n = 132) had good functional outcome (modified Rankin Scale score 0-2) and the mortality rate was 20.9% (n = 63) after 3 months. Compared to the anterior circulation, vertebrobasilar stroke patients had higher mortality. Patients with secondary hospital transportation had better outcomes after 3 months than in house treated patients. CONCLUSION: Our results document nationwide favourable outcome and safety rates of endovascular stroke treatment comparable to recent randomized trials. The ability to provide such data and the need to further optimize such an approach also underscore the contribution of respective registries. PMID- 26843096 TI - The evolution of the meatal chamber in crocodyliforms. AB - The unique outer ear of crocodylians consists of a large meatal chamber (MC) concealed by a pair of muscular earlids that shape a large part of the animal's head. This chamber is limited medially by the enlarged tympanic membrane. Yet, the anatomy of this distinctive and complex region is underexplored and its evolutionary history untraced. The osteology and soft tissues of the MC in extant crocodylians was analysed to describe it and establish osteological correlates within this region. A broad survey of the osteological correlates was conducted in major clades of fossil crocodyliforms to estimate evolutionary trends of the MC. The reorganization of the MC at the origin of crocodyliforms includes characters also present in more basal taxa such as 'sphenosuchians' as well as unique traits of crocodyliforms. Three major patterns are recognized in the MC of basal mesoeucrocodylians. The distinct 'thalattosuchian pattern' indicates that extensive modifications occurred in this clade of aquatic fossil crocodyliforms, even when multiple alternative phylogenetic positions are taken into account. Some traits already established in putative closely related clades are absent or modified in this group. The 'basal notosuchian/sebecian pattern' is widespread among basal metasuchians, and establishes for the first time characters maintained later in neosuchians and extant forms. The 'advanced notosuchian pattern' includes modifications of the MC possibly related to a terrestrial lifestyle and potentially a structure analogous to the mammalian pinna. The main variation in the MC of neosuchians is associated with the homoplastic secondary opening of the cranioquadrate passage. The inferred phylogenetic trends in the crocodyliform MC suggest the great anatomical disparity in this region followed a complex evolutionary pattern, and tympanic hearing played an important role in the origin and diversification of Crocodyliformes. PMID- 26843097 TI - Commentary on: Challenging Breast Augmentations: The Influence of Preoperative Anatomical Features on the Final Result. PMID- 26843098 TI - Commentary on: Visual, Physiological, and Aesthetic Factors and Pitfalls in Asian Blepharoplasty. PMID- 26843100 TI - Approach to Isoindolinones, Isoquinolinones, and THIQs via Lewis Acid-Catalyzed Domino Strecker-Lactamization/Alkylations. AB - A one-pot, three-component synthesis of widely substituted isoindolinones and isoquinolinones, featuring a Lewis acid-catalyzed efficient Strecker reaction and lactamization sequence, affording products in good to high yields is reported. The method has also been extended to the synthesis of tetrahydroisoquinolines (THIQs) in high yields. PMID- 26843099 TI - The Relationship of Bacterial Biofilms and Capsular Contracture in Breast Implants. AB - Capsular contracture is a common sequelae of implant-based breast augmentation. Despite its prevalence, the etiology of capsular contracture remains controversial. Numerous studies have identified microbial biofilms on various implantable materials, including breast implants. Furthermore, biofilms have been implicated in subclinical infections associated with other surgical implants. In this review, we discuss microbial biofilms as a potential etiology of capsular contracture. The review also outlines the key diagnostic modalities available to identify the possible infectious agents found in biofilm, as well as available preventative and treatment measures. PMID- 26843103 TI - Microhabitat Differences in the Benthic Substrata Affect Parasitism in a Pulmonate Snail Host, Helisoma anceps. AB - The microhabitats in which hosts live can potentially influence the ability and success of parasites in finding and infecting these hosts. The infection dynamics of both digenetic trematode parasites and a nematode parasite (Daubaylia potomaca) infecting a pulmonate snail, Helisoma anceps , were observed in a small North Carolina lake using 3 different classifications of substratum type based on percent coverage by leaves and debris. There were no differences in snail site occupancy or density between substratum types, but small-scale differences in microhabitat impacted parasite prevalence and intensity in their gastropod hosts. Snails inhabiting substrata covered in more leaf litter and debris had a lower prevalence and intensity of infection by all of the trematode species and life stages when compared to H. anceps inhabiting other substrata types, while only the intensity of infection was impacted in D. potomaca infections. These findings emphasize the importance of microhabitat, specifically its physical components, in influencing parasite infection in intermediate hosts and that small-scale differences may significantly affect the patterns of infection. PMID- 26843102 TI - Rivaroxaban: can we trust the evidence? PMID- 26843104 TI - The effect of internalization and other psychologic factors on the remission and severity of wheeze in children. AB - BACKGROUND: Asthma prevalence in Latin America is high and continues to increase. There is evidence that the psychologic characteristics of the child are associated with greater asthma morbidity. This study aimed to investigate the independent effect of internalizing/externalizing problems on two asthma/wheeze outcomes: (i) remission and (ii) progression to severity on Latin American children with mild asthma symptoms at baseline. METHODS: This was a prospective study in a cohort of 371 asthmatic children living in a poor urban area in Salvador, Brazil. The psychologic characteristics of the child were assessed using the Child Behavior Checklist (CBCL), and wheezing was defined using the ISAAC questionnaire at the start and end of follow-up. A multiple logistic regression model with random effects was used to examine the association between the psychologic components and both outcomes. RESULTS: Remission of symptoms of wheeze was observed among 229 (61.73%) children. Remission was 56% lower among children with internalizing problems (OR = 0.54, 95% CI 0.33-0.87, p = 0.01). In addition, we found that 19 (8.76%) of the children acquired severe symptoms during follow-up and there was strong evidence of the effect of internalizing problems in increasing the risk of progression to severe wheeze symptoms (OR = 4.03, 95% CI 1.39-11.70, p = 0.01). CONCLUSIONS: Children with internalizing problems but not externalizing had less remission of wheezing, and a higher risk of acquiring severe symptoms. These results highlight the importance of psychologic care for children with asthma, to improve the prognosis of this condition. PMID- 26843101 TI - Circulating matrix metalloproteinases in children with diabetic ketoacidosis. AB - BACKGROUND AND OBJECTIVE: Matrix metalloproteinases (MMPs) mediate blood-brain barrier dysfunction in inflammatory disease states. Our objective was to compare circulating MMPs in children with diabetic ketoacidosis (DKA) to children with type 1 diabetes mellitus without DKA. RESEARCH DESIGN AND METHODS: This was a prospective study performed at five tertiary-care pediatric hospitals. We measured plasma MMP-2, MMP-3, and MMP-9 early during DKA (time 1; within 2 h of beginning intravenous fluids) and during therapy (time 2; median 8 h; range: 4-16 h). The primary outcome was MMP levels in 34 children with DKA vs. 23 children with type 1 diabetes without DKA. Secondary outcomes included correlations between MMPs and measures of DKA severity. RESULTS: In children with DKA compared with diabetes controls, circulating MMP-2 levels were lower (mean 77 vs. 244 ng/mL, p < 0.001), MMP-3 levels were similar (mean 5 vs. 4 ng/mL, p = 0.57), and MMP-9 levels were higher (mean 67 vs. 25 ng/mL, p = 0.002) early in DKA treatment. MMP-2 levels were correlated with pH at time 1 (r = 0.45, p = 0.018) and time 2 (r = 0.47, p = 0.015) and with initial serum bicarbonate at time 2 (r = 0.5, p = 0.008). MMP-9 levels correlated with hemoglobin A1c in DKA and diabetes controls, but remained significantly elevated in DKA after controlling for hemoglobin A1c (beta = -31.3, p = 0.04). CONCLUSIONS: Circulating MMP-2 levels are lower and MMP-9 levels are higher in children during DKA compared with levels in children with diabetes without DKA. Alterations in MMP expression could mediate BBB dysfunction occurring during DKA. PMID- 26843105 TI - Oxidative Stress Markers in Vitamin B12 Deficiency. AB - In this study, we report the status of oxidative stress markers in vitamin B12 deficiency and their relation to clinical, laboratory, and neurophysiological findings. Fifty-one subjects with serum vitamin B12 deficiency (<211 pg/ml) were included. Plasma glutathione (GSH), malondialdehyde (MDA) and serum total antioxidant capacity (TAC) were measured in the patients and 53 controls. These markers were also compared between subacute combined degeneration (SACD) and non SACD vitamin B12 deficiency patients groups as well as with normal controls. In the patients, GSH, MDA and TAC were correlated with demographic, clinical, hematological, biochemical, nerve conduction study (NCS), visual evoked potential (VEP) and somatosensory-evoked potential (SEP) findings. In the study group, 20 (39.2 %) patients had SACD manifesting with myeloneuropathy, cognitive or behavioral abnormalities, and 31(60.8 %) patients had non-SACD neurological manifestations. The GSH (2.46 +/- 0.32 vs. 2.70 +/- 0.36 mg/dl; P = 0.002) and TAC (2.13 +/- 0.38 vs. 2.33 +/- 0.24 nmol Trolox eq/l, P = 0.005) levels were lower, and MDA levels (4.01 +/- 0.69 vs. 3.00 +/- 0.45 nmol/ml, P < 0.001) were higher in B12 deficiency group compared with controls. Similar trend was found in SACD and non-SACD vitamin B12 deficiency groups. GSH levels correlated with abnormal VEP (r = 0.54; P < 0.01), TAC with female gender (r = 0.43; P = 0.002) and joint position impairment (r = -0.34; P = 0.01), and MDA with LDH (r = 0.41; P = 0.01). Vitamin B12 deficiency was associated with reduction in GSH and TAC and increase in MDA levels which were more marked in SACD compared to non-SACD group. PMID- 26843106 TI - Prolonged Effects of Silver Nanoparticles on p53/p21 Pathway-Mediated Proliferation, DNA Damage Response, and Methylation Parameters in HT22 Hippocampal Neuronal Cells. AB - It is widely accepted that silver nanoparticles (AgNPs) are toxic to biological systems. However, little is known about their actions at molecular level and the cytophysiological effects after AgNP removal. As nanoparticles are suggested a promising tool to transport drugs to the brain for use in neurological conditions, we used HT22 mouse hippocampal neuronal cells as a model to study AgNP-mediated effects after their removal from the cell culture medium. We selected a relatively low concentration of AgNPs, 5 MUg/ml, treated the cells for 48 h, and evaluated AgNP-induced cytophysiological effects after 96 h of AgNP removal. AgNP removal did not result in cytotoxicity. In contrast, AgNPs modulated HT22 cell cycle and proliferation and induced oxidative stress and 53BP1 recruitment, which were accompanied by elevated levels of p53 and p21. AgNP associated diminution in lamin B1 pools did not significantly affect the structure of the nucleus. No disruption in F-actin dynamics was observed upon AgNP treatment. Moreover, we showed for the first time that AgNPs stimulated changes in DNA methylation: the augmentation in 5-methylcytosine (5-mC) and DNMT1, DNMT2, DNMT3a, and DNMT3b levels were observed. The upregulation of DNMT2 may be a part of cellular stress response to AgNP treatment. Taken together, AgNP removal resulted in p53/p21-mediated inhibition of cell proliferation, oxidant based DNA damage response, and changes in DNA methylation patterns, which suggests that more attention should be paid to the possible outcomes in individuals exposed to nano-sized biomaterials. PMID- 26843107 TI - Tumor Necrosis Factor Receptor Associated Factors (TRAFs) 2 and 3 Form a Transcriptional Complex with Phosho-RNA Polymerase II and p65 in CD40 Ligand Activated Neuro2a Cells. AB - The tumor necrosis factor receptor-associated factors (TRAFs) have been classically described as adaptor proteins that function as solely cytosolic signaling intermediates for the TNF receptor superfamily, Toll-like receptors (TLRs), NOD, like receptors (NLRs), cytokine receptors, and others. In this study, we show for the first time that TRAFs are present within the cytoplasm and nucleus of Neuro2a cells and primary cortical neurons, and that TRAF2 and TRAF3 translocate into the nucleus within minutes of CD40L stimulation. Analysis of the transcriptional regulatory potential of TRAFs by luciferase assay revealed that each of the TRAFs differentially functions as a transcriptional activator or repressor in a cell-specific manner. Interestingly, ChIP-qPCR data demonstrate that TRAFs 2/3, p65, and pRNAPol II form part of a transcriptional complex on the Icam-1 gene promoter upon CD40L stimulation. We further determined that TRAF2 recruitment to the nucleus is critical for the ubiquitination of H2b, a transcription permissive epigenetic modification. Our findings demonstrate for the first time that TRAFs 2/3 participate in the formation of a CD40L-induced transcriptional complex in neuronal cells. PMID- 26843108 TI - A Comprehensive Meta-analysis of Genetic Associations Between Key Polymorphic Loci in DNA Repair Genes and Glioma Risk. AB - Genetic variants found in DNA repair genes (ERCC1, rs3212986; ERCC2, rs13181; ERCC4, rs1800067; ERCC5, rs17655; XRCC1, rs1799782, rs25487, rs25489; XRCC3, rs861539) have been reported to have an ambivalent association with the development of glioma. In the present study, a meta-analysis was conducted to confirm the relationship, taking heterogeneity of population into consideration. We analyzed 21 articles of 6 genes along with 8 single nucleotide polymorphisms (SNPs) (24,078 cases and 30,926 healthy individuals), which assessed the relationship between nucleotide excision, base excision, double-strand break repair gene, and the development of glioma under five models. All statistical analysis was implemented by the software of R 3.2.1, and the relationships between key polymorphic loci in DNA repair genes and glioma were quantified by the pooled odds ratio (OR) and 95 % confidential intervals. Overall, the synthesized evidence demonstrated that the SNP of rs13181 and rs1799782 significantly increased the risk of glioma whereas SNP of rs1800067 were significantly associated with a decrease in the risk of glioma. Additionally, subgroup analyses of 8 SNPs by ethnicity indicated that the mutation of rs13181, rs1800067 were apparently protective factors of glioma among Asians, while the mutation of rs13181 was a risk factors of glioma in Caucasians. Furthermore, the mutation of rs1799782 significantly raises the risk of glioma for Asian. Our study suggested that rs13181*C and rs1799782*A are risk alleles for glioma; rs1800067*A are beneficial alleles for decreased susceptibility to glioma. Future studies with large sample size and other races are strongly recommended to confirm the results from this study. PMID- 26843109 TI - Bmi1 Regulates the Proliferation of Cochlear Supporting Cells Via the Canonical Wnt Signaling Pathway. AB - Cochlear supporting cells (SCs), which include the cochlear progenitor cells, have been shown to be a promising resource for hair cell (HC) regeneration, but the mechanisms underlying the initiation and regulation of postnatal cochlear SC proliferation are not yet fully understood. Bmi1 is a member of the Polycomb protein family and has been reported to regulate the proliferation of stem cells and progenitor cells in multiple organs. In this study, we investigated the role of Bmi1 in regulating SC and progenitor cell proliferation in neonatal mice cochleae. We first showed that knockout of Bmi1 significantly inhibited the proliferation of SCs and Lgr5-positive progenitor cells after neomycin injury in neonatal mice in vitro, and we then showed that Bmi1 deficiency significantly reduced the sphere-forming ability of the organ of Corti and Lgr5-positive progenitor cells in neonatal mice. These results suggested that Bmi1 is required for the initiation of SC and progenitor cell proliferation in neonatal mice. Next, we found that DKK1 expression was significantly upregulated, while beta catenin and Lgr5 expression were significantly downregulated in neonatal Bmi1-/- mice compared to wild-type controls. The observation that Bmi1 knockout downregulates Wnt signaling provides compelling evidence that Bmi1 is required for the Wnt signaling pathway. Furthermore, the exogenous Wnt agonist BIO overcame the downregulation of SC proliferation in Bmi1-/- mice, suggesting that Bmi1 knockout might inhibit the proliferation of SCs via downregulation of the canonical Wnt signaling pathway. Our findings demonstrate that Bmi1 plays an important role in regulating the proliferation of cochlear SCs and Lgr5-positive progenitor cells in neonatal mice through the Wnt signaling pathway, and this suggests that Bmi1 might be a new therapeutic target for HC regeneration. PMID- 26843110 TI - Klotho Gene and Selective Serotonin Reuptake Inhibitors: Response to Treatment in Late-Life Major Depressive Disorder. AB - Klotho protein, encoded by the Klotho gene (KL) at locus 13q12, is an antiaging hormone-like protein playing a pivotal role in cell metabolism homeostasis and associated to longevity and age-related diseases. In particular, altered cell metabolism in central nervous system may influence the behavior of serotoninergic neurons. The role of KL in the response to treatment with selective serotonin reuptake inhibitors (SSRIs) in late-life depressive syndromes and late-life major depressive disorder (MDD) is unclear. We genotyped three single-nucleotide polymorphisms (SNPs) of KL in 329 older patients with diagnosis of late-life MDD, treated with SSRIs and evaluated with the Hamilton Rating Scale for Depression 21 items (HRSD-21) at baseline and after 6 months. A reduction >=50 and <10 % in HDRS-21 score was considered as response or nonresponse to therapy, respectively, and the values of reduction between 10 and 49 % as poor responders. After 6 months of SSRI treatment, 176 patients responded, 54 patients did not respond and 99 patients showed a poor response. Ordinal logistic models showed a significant association between mutation of SNP rs1207568 and responders and, similarly, for each unitary risk allele increase overlapping results were found. Conversely, a significantly higher frequency of the minor genotype of SNP rs9536314 was found in nonresponders. Considering the pre-post differences of HRSD-21 scores as a continue variable, we confirmed a significant improvement of depressive symptoms after treatment in patients carrying at least one minor allele at rs1207568 and a worse response in patients homozygous for the minor allele at rs9536314. Our results were the first that suggested a possible role of KL in the complex pathway of SSRI response in late-life MDD. PMID- 26843111 TI - Pax2-Islet1 Transgenic Mice Are Hyperactive and Have Altered Cerebellar Foliation. AB - The programming of cell fate by transcription factors requires precise regulation of their time and level of expression. The LIM-homeodomain transcription factor Islet1 (Isl1) is involved in cell-fate specification of motor neurons, and it may play a similar role in the inner ear. In order to study its role in the regulation of vestibulo-motor development, we investigated a transgenic mouse expressing Isl1 under the Pax2 promoter control (Tg +/- ). The transgenic mice show altered level, time, and place of expression of Isl1 but are viable. However, Tg +/- mice exhibit hyperactivity, including circling behavior, and progressive age-related decline in hearing, which has been reported previously. Here, we describe the molecular and morphological changes in the cerebellum and vestibular system that may cause the hyperactivity of Tg +/- mice. The transgene altered the formation of folia in the cerebellum, the distribution of calretinin labeled unipolar brush cells, and reduced the size of the cerebellum, inferior colliculus, and saccule. Age-related progressive reduction of calbindin expression was detected in Purkinje cells in the transgenic cerebella. The hyperactivity of Tg +/- mice is reduced upon the administration of picrotoxin, a non-competitive channel blocker for the gamma-aminobutyric acid (GABA) receptor chloride channels. This suggests that the overexpression of Isl1 significantly affects the functions of GABAergic neurons. We demonstrate that the overexpression of Isl1 affects the development and function of the cerebello vestibular system, resulting in hyperactivity. PMID- 26843112 TI - Endovascular Treatment Versus Intravenous Thrombolysis for Acute Ischemic Stroke: a Quantitative Review and Meta-Analysis of 21 Randomized Trials. AB - Emerging studies suggest that endovascular treatment (EVT) may be superior to intravenous thrombolysis for acute ischemic stroke (AIS). We performed a systematic review and meta-analysis of all randomized controlled trials (RCTs) to assess the efficacy and safety of endovascular treatment in patients with acute ischemic stroke as compared with intravenous thrombolysis. We assessed RCTs investigating EVT versus intravenous thrombolysis (IVT) published up to June 2015. In total, 21 studies of 4473 patients were included in the systematic review and meta-analysis. EVT significantly improved functional outcome at 90 days (risk ratio (RR) 1.35, 95 % confidence interval (CI) 1.18 to 1.55, I 2 = 61 %) and reduced the mortality (RR 0.81, 95 % CI 0.68 to 0.95, I 2 = 0 %), with similar symptomatic hemorrhagic transformation (SHT) rate (RR 1.12, 95 % CI 0.88 to 1.44, I 2 = 0 %). Based on the current data, endovascular therapy may produce good clinical outcomes with similar symptomatic hemorrhage and mortality as compared with intravenous thrombolysis in acute ischemic stroke. This advancing intervention is a landmark change in stroke treatment and could be of huge potential benefit to patients worldwide. PMID- 26843113 TI - Lentiviral Vector-Induced Overexpression of RGMa in the Hippocampus Suppresses Seizures and Mossy Fiber Sprouting. AB - Repulsive guidance molecule a (RGMa) is a membrane-bound protein that inhibits axon outgrowth in the central nervous system. Temporal lobe epilepsy (TLE) is a common neurological disorder characterized by recurrent spontaneous seizures. To explore the role of RGMa in epilepsy, we investigated the expression of RGMa in patients with TLE, pilocarpine-induced rat model, and pentylenetetrazol kindling model of epilepsy, and then we performed behavioral, histological, and electrophysiological analysis by lentivirus-mediated overexpression of RGMa in the hippocampus of animal model. We found that RGMa was significantly decreased in TLE patients and in experimental rats from 6 h to 60 days after pilocarpine induced seizures. In two types of epileptic animal models, pilocarpine-induced model and pentylenetetrazol kindling model, overexpression of RGMa in the hippocampus of rats exerted seizure-suppressant effects. The reduced spontaneous seizures were accompanied by attenuation of hippocampal mossy fiber sprouting. In addition, overexpression of RGMa inhibited hyperexcitability of hippocampal neurons via suppressing NMDAR-mediated currents in Mg2+-free-induced organotypic slice model. Collectively, these results demonstrate that overexpression of RGMa could be an alternative strategy for epilepsy therapy. PMID- 26843114 TI - MicroRNA Profiling Identifies miR-196a as Differentially Expressed in Childhood Adrenoleukodystrophy and Adult Adrenomyeloneuropathy. AB - X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene, leading to a defect in the peroxisomal adrenoleukodystrophy protein (ALDP), which inhibits the beta-oxidation of very long chain fatty acids (VLCFAs). It is a complex disease where the same mutation in the peroxisomal ABCD1 can lead to clinically diverse phenotypes ranging from the fatal disorder of cerebral ALD (cALD) to mild adult disorder of adrenomyeloneuropathy (AMN). This suggests a role of epigenetic factors/modifier genes in disease progression of X-ALD which is not understood at present. To examine the possible role of microRNA (miRNA) in X-ALD disease mechanisms for differences in cALD and AMN phenotype, we profiled 1008 known miRNA in cALD, AMN, and normal human skin fibroblasts using miScript miRNA PCR array (Qiagen) and selected miRNAs which had differential expression in cALD and AMN fibroblasts. Eleven miRNA which were differentially regulated in cALD and AMN fibroblasts were identified. miR-196a showed a significant differential expression between cALD and AMN and is further characterized for target gene regulation. The predicted role of miR-196a in inhibition of inflammatory signaling factors (IKKalpha and IKKbeta) and ELOVL1 expression suggests the pathological role of altered expression of miR-196a. This study indicates that miR-196a participated in differential regulation of ELOVL1 and inflammatory response between cALD as compared to AMN and may be a possible biomarker to differentiate between cALD and AMN. PMID- 26843116 TI - Serum Androgen Levels and Sexual Function Before and One Year After Treatment of Uterine Cervical Cancer: A Pilot Study. AB - INTRODUCTION: Radiotherapy or radical hysterectomy with salpingo-oophorectomy (SOE) as treatment for uterine cervical cancer causes estrogen deprivation in premenopausal women. The effects on androgen production have rarely been examined but could be relevant for survivors of cervical cancer because insufficiency has been associated with low sexual function. AIM: To investigate the effects of pelvic radiotherapy, hysterectomy with SOE, or surgery without SOE on androgen levels and to explore potential associations with sexual function. METHODS: Patients with cervical cancer (N = 60) were prospectively examined through blood sampling and questionnaires before and 1 year after treatments. MAIN OUTCOME MEASURES: Serum testosterone (measured by liquid chromatography and tandem mass spectrometry), sex hormone-binding globulin, androstenedione, dehydroepiandrosterone sulfate, follicle-stimulating hormone, luteinizing hormone, and estradiol levels and Female Sexual Function Index scores. RESULTS: In women treated with radiotherapy (n = 38), median total and free testosterone levels were significantly decreased at 1-year follow-up compared with baseline in premenopausal women (n = 16; total testosterone -29%, P = .01; free testosterone 22%, P = .007) and postmenopausal women (n = 22; total testosterone -25%, P = .03; free testosterone -29%, P = .03). Androstenedione was decreased in premenopausal women only and dehydroepiandrosterone sulfate was decreased in postmenopausal women only after radiotherapy. In women treated with hysterectomy and SOE (n = 10), testosterone levels were lower but not significantly lower, and there was no change in those having surgery without SOE (n = 12). Female Sexual Function Index scores lower than 26.5 in sexually active women were reported by 80% 1 year after radiotherapy, by 44% after hysterectomy with SOE, and by 40% after surgery without SOE, with no significant differences compared with baseline values. No direct correlation between androgen levels and Female Sexual Function Index scores were found at 1-year follow-up. CONCLUSION: Total and free testosterone levels decreased slightly but significantly after pelvic radiotherapy in pre- and postmenopausal women. The clinical importance of this decrease is unclear, but androgen levels were not directly related to sexual function in this pilot setting. PMID- 26843118 TI - Adaptive outflow boundary conditions improve post-operative predictions after repair of peripheral pulmonary artery stenosis. AB - Peripheral pulmonary artery stenosis (PPS) is a congenital abnormality resulting in pulmonary blood flow disparity and right ventricular hypertension. Despite recent advance in catheter-based interventions, surgical reconstruction is still preferred to treat complex PPS. However optimal surgical strategies remain unclear. It would be of great benefit to be able to predict post-operative hemodynamics to assist with surgical planning toward optimizing outcomes. While image-based computational fluid dynamics has been used in cardiovascular surgical planning, most studies have focused on the impact of local geometric changes on hemodynamic performance. Previous experimental studies suggest morphological changes in the pulmonary arteries not only alter local hemodynamics but also lead to distal pulmonary adaptation. In this proof of concept study, a constant shear stress hypothesis and structured pulmonary trees are used to derive adaptive outflow boundary conditions for post-operative simulations. Patient-specific simulations showed the adaptive outflow boundary conditions by the constant shear stress model to provide better predictions of pulmonary flow distribution than the conventional strategy of maintaining outflow boundary conditions. On average, the relative difference, when compared to the gold standard clinical test, in blood flow distribution to the right lung is reduced from 20 to 4 %. This suggests adaptive outflow boundary conditions should be incorporated into post operative modeling in patients with complex PPS. PMID- 26843115 TI - Oxidative Modification and Its Implications for the Neurodegeneration of Parkinson's Disease. AB - Parkinson's disease (PD) is the second most common neurodegenerative disease. The major characteristics of PD include the loss of dopaminergic neurons in the substantia nigra and Lewy body depositions. Genetic defects, environment toxicants, and aging have been recognized as risk factors for the development of PD. Currently, although the pathogenesis of PD is still obscure, overwhelming evidence demonstrates that oxidative stress plays a central role in the progress of PD. Reactive oxygen species (ROS) function mainly through chemical reactions with atomic targets that lead to covalent oxidative modifications. Through the oxidative modification of ions, amino acids, amines, and nucleic acids, ROS exert augmented effects on the structures and functions of multiple macromolecules. These oxidative modifications can affect nucleic acid stability by oxidizing RNA, increasing mitochondrial DNA (mtDNA) mutation, and launching translesion synthesis (TLS); disturb protein homeostasis by accelerating alpha-synuclein aggregation, parkin aggregation, and proteasome dissociation; modulate dopamine release by activating ATP-sensitive potassium channels (KATP) and inactivating neuronal nicotinic acetylcholine receptors (nAChRs); and influence cellular self defenses by promoting the cytoprotective effects of DJ-1 and PTEN-induced putative kinase 1 (PINK1) while inducing Akt dysregulation. Based on the above facts, we propose that various oxidative modifications may affect nucleic acid stability, protein homeostasis, the functionality of ion channels, and cellular self-defenses and that these processes lead to protein misfolding, dopamine depletion, and further neuronal death in PD. PMID- 26843117 TI - Disposition of flavonoids via recycling: Direct biliary excretion of enterically or extrahepatically derived flavonoid glucuronides. AB - SCOPE: Enterohepatic recycling is often thought to involve mostly phase II metabolites generated in the liver. This study aims to determine if direct biliary excretion of extrahepatically generated glucuronides would also enable recycling. METHODS AND RESULTS: Conventional and modified intestinal perfusion models along with intestinal and liver microsomes were used to determine the contribution of extrahepatically derived glucuronides. Glucuronidation of four flavonoids (genistein, biochanin A, apigenin, and chrysin at 2.5-20 MUM) were generally more rapid in the hepatic than intestinal microsomes. Furthermore, when aglycones (at 10 MUM each) were perfused, larger (1.7-9 fold) amounts of glucuronides were found in the bile than in the luminal perfusate. However, higher concentrations of glucuronides were not found in jugular vein than portal vein, and apigenin glucuronide actually displayed a significantly lower concentration in jugular vein (<1 nM) than portal vein (~4 nM). A direct portal infusion of four flavonoid glucuronides (5.9-10.4 MUM perfused at 2 mL/h) showed that the vast majority (>65%) of the glucuronides (except for biochanin A glucuronide) administered were efficiently excreted into the bile. CONCLUSION: Direct biliary excretion of extrahepatically generated flavonoid glucuronides is a highly efficient clearance mechanism, which should enable enterohepatic recycling of flavonoids without hepatic conjugating enzymes. PMID- 26843119 TI - Expression of grapevine AINTEGUMENTA-like genes is associated with variation in ovary and berry size. AB - Fruit size is a highly important trait for most fruit and vegetable crops. This trait has been a main selection target and could be involved in divergent selection processes leading to the differentiation between modern table and wine cultivars. Even though its determination is highly influenced by cultural practices, several regions within the grapevine genome have been identified affecting berry size, either directly or indirectly through their effect on seed content. Using grapevine seeded cultivars, we have analyzed the relationship between ovary cell number and the final size of ovaries and berry fruits. We also performed the characterization of the grapevine AINTEGUMENTA-LIKE family, since it is well reported in Arabidopsis that AINTEGUMENTA (ANT) regulates cell proliferation and organ growth in flower organ primordia by maintaining the meristematic competence of cells during organogenesis. Here we show that orthologous grapevine gene expression associate with flower developmental stages suggesting a similar biological role for this gene family in this species. Moreover, we detected a correlation between those organs size and the level of expression of VviANT1 the grapevine homolog of AtANT. This grapevine gene also co localizes in linkage group 18 with the confidence interval of a previously detected QTL for berry size. Thus our results suggest the involvement of ANT in the regulation of berry size in grapevine. PMID- 26843121 TI - Oral phenotype and variation in focal dermal hypoplasia. AB - Focal dermal hypoplasia (FDH) or Goltz Syndrome (OMIM# 305600) is an X-linked dominant ectodermal dysplasia caused by mutations in the PORCN gene. This gene encodes an endoplasmic reticulum transmembrane protein that is involved in processing the embryonically critical WNT signaling proteins. Individuals diagnosed with FDH were recruited to participate in the study through the National Foundation for Ectodermal Dysplasia. Individuals were evaluated to characterize the FDH phenotype. Each participant completed a brief dental survey and oral evaluation using artificial light. To identify the oral soft and hard tissue findings 19 individuals (16 female and 3 male) participated with a median age of 10 years (range 2-56 years). Soft and hard tissue defects were present in 68% (13) and 94% (18) of the patients, respectively. Dental anomalies were highly prevalent with 68% (13) demonstrating vertical enamel grooving, 52% (10) having peg shaped tooth deformities, and 78% (15) having enamel hypoplasia with or without discoloration. Cleft lip and cleft palate presented in 15% (3) of the participants. Other findings included 57% (11) having intra-oral lipoma or papilloma with no site predilection. Dental malocclusions were common with 63% (12) having some degree of malocclusion with 15% (3) of participants having class III malocclusion with an anterior dental cross bite. Participants frequently reported speech problems or difficulty with chewing (73%; N = 14). This study shows there is marked variation in the oral phenotype of individuals with FDH and underscores the important role of WNT signaling in oro-facial development. PMID- 26843120 TI - Blood pressure-lowering effect of Korean red ginseng associated with decreased circulating Lp-PLA2 activity and lysophosphatidylcholines and increased dihydrobiopterin level in prehypertensive subjects. AB - We evaluated the effects of red ginseng consumption on blood pressure (BP) and the fasting plasma metabolome. This randomized, double-blind, placebo-controlled study included nonobese, nondiabetic, prehypertensive subjects consuming 10 capsules daily containing 5 g red ginseng (n=31) or placebo (n=31). Fasting plasma metabolome profiles were obtained using ultra performance liquid chromatography-linear trap quadrupole Orbitrap MS. After 12 weeks, participants consuming red ginseng showed reductions of 6.5 and 5.0 mm Hg in systolic and diastolic BP, respectively. Compared with controls, those consuming red ginseng showed greater reductions in changed values of systolic BP, diastolic BP and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, after adjusting for baseline values. In addition, the red ginseng group showed a greater increase in dihydrobiopterin levels and greater decrease in palmitic amide and lysophosphatidylcholines (lysoPCs). The change in diastolic BP positively correlated with changes in lysoPCs and Lp-PLA2 activity. The BP-lowering effect of red ginseng is associated with decreased Lp-PLA2 and lysoPCs and increased dihydrobiopterin levels in prehypertensive subjects (ClinicalTrials.gov: NCT02326766). PMID- 26843122 TI - Pure &crystallized 2D Boron Nitride sheets synthesized via a novel process coupling both PDCs and SPS methods. AB - Within the context of emergent researches linked to graphene, it is well known that h-BN nanosheets (BNNSs), also referred as 2D BN, are considered as the best candidate for replacing SiO2 as dielectric support or capping layers for graphene. As a consequence, the development of a novel alternative source for highly crystallized h-BN crystals, suitable for a further exfoliation, is a prime scientific issue. This paper proposes a promising approach to synthesize pure and well-crystallized h-BN flakes, which can be easily exfoliated into BNNSs. This new accessible production process represents a relevant alternative source of supply in response to the increasing need of high quality BNNSs. The synthesis strategy to prepare pure h-BN is based on a unique combination of the Polymer Derived Ceramics (PDCs) route with the Spark Plasma Sintering (SPS) process. Through a multi-scale chemical and structural investigation, it is clearly shown that obtained flakes are large (up to 30 MUm), defect-free and well crystallized, which are key-characteristics for a subsequent exfoliation into relevant BNNSs. PMID- 26843123 TI - Multimodality cardiac imaging in Turner syndrome. AB - Congenital and acquired cardiovascular diseases contribute significantly to the threefold elevated risk of premature death in Turner syndrome. A multitude of cardiovascular anomalies and disorders, many of which deleteriously impact morbidity and mortality, is frequently left undetected and untreated because of poor adherence to screening programmes and complex clinical presentations. Imaging is essential for timely and effective primary and secondary disease prophylaxis that may alleviate the severe impact of cardiovascular disease in Turner syndrome. This review illustrates how cardiovascular disease in Turner syndrome manifests in a complex manner that ranges in severity from incidental findings to potentially fatal anomalies. Recommendations regarding the use of imaging for screening and surveillance of cardiovascular disease in Turner syndrome are made, emphasising the key role of non-invasive and invasive cardiovascular imaging to the management of all patients with Turner syndrome. PMID- 26843125 TI - Creep turns linear in narrow ferromagnetic nanostrips. AB - The motion of domain walls in magnetic materials is a typical example of a creep process, usually characterised by a stretched exponential velocity-force relation. By performing large-scale micromagnetic simulations, and analyzing an extended 1D model which takes the effects of finite temperatures and material defects into account, we show that this creep scaling law breaks down in sufficiently narrow ferromagnetic strips. Our analysis of current-driven transverse domain wall motion in disordered Permalloy nanostrips reveals instead a creep regime with a linear dependence of the domain wall velocity on the applied field or current density. This originates from the essentially point-like nature of domain walls moving in narrow, line- like disordered nanostrips. An analogous linear relation is found also by analyzing existing experimental data on field-driven domain wall motion in perpendicularly magnetised media. PMID- 26843126 TI - A Rare Presentation of Chest Wall Chondrosarcoma as a Breast Mass. PMID- 26843124 TI - PAF-Wnt signaling-induced cell plasticity is required for maintenance of breast cancer cell stemness. AB - Cancer stem cells (CSCs) contribute to tumour heterogeneity, therapy resistance and metastasis. However, the regulatory mechanisms of cancer cell stemness remain elusive. Here we identify PCNA-associated factor (PAF) as a key molecule that controls cancer cell stemness. PAF is highly expressed in breast cancer cells but not in mammary epithelial cells (MECs). In MECs, ectopic expression of PAF induces anchorage-independent cell growth and breast CSC marker expression. In mouse models, conditional PAF expression induces mammary ductal hyperplasia. Moreover, PAF expression endows MECs with a self-renewing capacity and cell heterogeneity generation via Wnt signalling. Conversely, ablation of endogenous PAF induces the loss of breast cancer cell stemness. Further cancer drug repurposing approaches reveal that NVP-AUY922 downregulates PAF and decreases breast cancer cell stemness. Our results unveil an unsuspected role of the PAF Wnt signalling axis in modulating cell plasticity, which is required for the maintenance of breast cancer cell stemness. PMID- 26843127 TI - High mortality in patients presenting with acute pulmonary embolism and elevated INR not on anticoagulant therapy. AB - The prognostic significance of patients presenting with pulmonary embolism (PE) and elevated International Normalised Ratio (INR) not on anticoagulant therapy has not been described. We investigated whether these patients had higher mortality compared to patients with normal INR. A retrospective study of patients admitted to a tertiary hospital with acute PE from 2000 to 2012 was undertaken, with study outcomes tracked using a state-wide death registry. Patients were excluded if they were taking anticoagulants or had inadequate documentation of their INR and medication status. Of the 1,039 patients identified, 94 (9 %) had an elevated INR (> 1.2) in the absence of anticoagulant use. These patients had higher mortality at six months follow-up (26 % vs 6 %, p< 0.001) compared to controls (INR <= 1.2). An INR > 1.2 at diagnosis was an independent predictor of death at six months post-PE (hazard ratio [HR] 2.9, 95 % confidence interval [CI] 1.8-4.7, p< 0.001). The addition of INR to a multivariable model that included the simplified pulmonary embolism severity index (sPESI), chest pain, and serum sodium led to a significant net reclassification improvement estimated at 8.1 %. The final model's C statistic increased significantly by 0.04 (95 % CI 0.01-0.08, p=0.03) to 0.83 compared to sPESI alone (0.79). In summary, patients presenting with acute PE and elevated INR while not on anticoagulant therapy appear to be at high risk of death. Future validation studies in independent cohorts will clarify if this novel finding can be usefully incorporated into clinical decision making in patients with acute PE. PMID- 26843129 TI - Hybrid coordination-network-engineering for bridging cascaded channels to activate long persistent phosphorescence in the second biological window. AB - We present a novel "Top-down" strategy to design the long phosphorescent phosphors in the second biological transparency window via energy transfer. Inherence in this approach to material design involves an ingenious engineering for hybridizing the coordination networks of hosts, tailoring the topochemical configuration of dopants, and bridging a cascaded tunnel for transferring the persistent energy from traps, to sensitizers and then to acceptors. Another significance of this endeavour is to highlight a rational scheme for functionally important hosts and dopants, Cr/Nd co-doped Zn1-xCaxGa2O4 solid solutions. Such solid-solution is employed as an optimized host to take advantage of its characteristic trap site level to establish an electron reservoir and network parameters for the precipitation of activators Nd(3+) and Cr(3+). The results reveal that the strategy employed here has the great potential, as well as opens new opportunities for future new-wavelength, NIR phosphorescent phosphors fabrication with many potential multifunctional bio-imaging applications. PMID- 26843131 TI - Identification of breast cancer margins using intraoperative near-infrared imaging. AB - BACKGROUND AND OBJECTIVES: Current methods of intraoperative breast cancer margin assessment are labor intensive, not fully reliable, and time consuming; therefore novel strategies are necessary. We hypothesized that near infrared (NIR) intraoperative molecular imaging using systemic indocyanine green (ICG) would be helpful in discerning tumor margins. METHODS: A mammary cancer cell line, 4T1, was used to establish tumors in mouse flanks (n = 60). Tumors were excised 24 hr after intravenous ICG. Assessment of residual tumor in the wound bed was performed using a combination of NIR imaging and traditional method (by visual inspection and palpation) versus traditional method alone. Next we performed a clinical trial to evaluate the role of NIR imaging after systemic ICG for the margin assessment of 12 patients undergoing breast-conserving surgery. RESULTS: Traditional margin assessment identified 30% of positive margins while NIR imaging identified 90% of positive margins. In our clinical trial, all tumors were detected by NIR imaging and there was fluorescent evidence of residual tumor in the tumor bed in 6 of the 12 patients. None of these patients had positive margins on pathology. CONCLUSIONS: Systemic ICG reliably accumulates in breast cancers in murine models as well as human breast cancer. While NIR imaging is helpful for detection of retained tumor margins in our animal model, intraoperative imaging for precise margin detection will need further refinement before clinical value can be obtained. J. Surg. Oncol. 2016;113:508-514. (c) 2016 Wiley Periodicals, Inc. PMID- 26843132 TI - Hard sphere packings within cylinders. AB - Arrangements of identical hard spheres confined to a cylinder with hard walls have been used to model experimental systems, such as fullerenes in nanotubes and colloidal wire assembly. Finding the densest configurations, called close packings, of hard spheres of diameter sigma in a cylinder of diameter D is a purely geometric problem that grows increasingly complex as D/sigma increases, and little is thus known about the regime for D > 2.873sigma. In this work, we extend the identification of close packings up to D = 4.00sigma by adapting Torquato-Jiao's adaptive-shrinking-cell formulation and sequential-linear programming (SLP) technique. We identify 17 new structures, almost all of them chiral. Beyond D ~ 2.85sigma, most of the structures consist of an outer shell and an inner core that compete for being close packed. In some cases, the shell adopts its own maximum density configuration, and the stacking of core spheres within it is quasiperiodic. In other cases, an interplay between the two components is observed, which may result in simple periodic structures. In yet other cases, the very distinction between the core and shell vanishes, resulting in more exotic packing geometries, including some that are three-dimensional extensions of structures obtained from packing hard disks in a circle. PMID- 26843130 TI - Human oral isolate Lactobacillus fermentum AGR1487 induces a pro-inflammatory response in germ-free rat colons. AB - Lactobacilli are thought to be beneficial for human health, with lactobacilli associated infections being confined to immune-compromised individuals. However, Lactobacillus fermentum AGR1487 negatively affects barrier integrity in vitro so we hypothesized that it caused a pro-inflammatory response in the host. We compared germ-free rats inoculated with AGR1487 to those inoculated with another L. fermentum strain, AGR1485, which does not affect in vitro barrier integrity. We showed that rats inoculated with AGR1487 had more inflammatory cells in their colon, higher levels of inflammatory biomarkers, and increased colonic gene expression of pro-inflammatory pathways. In addition, our in vitro studies showed that AGR1487 had a greater capacity to activate TLR signaling and induce pro inflammatory cytokines in immune cells. This study indicates the potential of strains of the same species to differentially elicit inflammatory responses in the host and highlights the importance of strain characterization in probiotic approaches to treat inflammatory disorders. PMID- 26843133 TI - Relationships between nutritional knowledge, obesity, and sleep disorder severity. AB - Obstructive sleep apnea affects 20% of the adult population. Weight control is considered the best non-medical means of managing the condition, therefore improving nutritional knowledge in individuals may be an appropriate strategy. This study aimed to describe the relationship between nutritional knowledge and: (i) sleep disorder severity; (ii) body mass index; and (iii) demographic characteristics in persons suspected of obstructive sleep apnea. Nutrition knowledge scores were also compared with the general population. Consecutive newly-referred patients attending the sleep laboratory for diagnostic polysomnography were invited to participate. Those who consented (n = 97) were asked to complete a touchscreen survey. Apnea-hypopnea index to measure sleep disorder severity and anthropometric measurements were obtained from the clinic. A quarter of participants were diagnosed with severe obstructive sleep apnea; and a majority (88%) were classed as being overweight or obese. The overall mean nutrition knowledge score was 58.4 +/- 11.6 (out of 93). Nutrition knowledge was not associated with sleep disorder severity, body mass index or gender. The only significant difference detected was in relation to age, with older (>=35 years) participants demonstrating greater knowledge in the 'food choices' domain compared with their younger counterparts (18-34 years; P < 0.030). Knowledge scores were similar to the general population. The findings suggest that nutrition knowledge alone is not an important target for weight control interventions for people with obstructive sleep apnea. However, given the complexities of sleep disorders, it may complement other strategies. PMID- 26843134 TI - MicroRNA-26b Enhances the Radiosensitivity of Hepatocellular Carcinoma Cells by Targeting EphA2. AB - Sensitizing hepatocellular carcinoma (HCC) cells to irradiation is important to achieve satisfactory therapeutic effect with low-dose radiotherapy. Erythropoietin-producing hepatocellular carcinoma A2 (EphA2) is a member of the Eph receptor family that constitutes the largest family of tyrosine kinase receptors. EphA2 overexpression is one of the poor prognostic factors in many progressive cancers. Importantly, EphA2 is a potential target of microRNA-26b (miR-26b), and miR-26b expression is down-regulated in several types of cancer. In this study, we measured the expression levels of miR-26b and EphA2 protein in seven human HCC cell lines by quantitative PCR and western blot analysis, respectively. Overall, lower miR-26b expression levels tended to be associated with higher EphA2 levels in HCC cell lines. Among the cell lines examined, 97H HCC cells expressed the lowest level of miR-26b and highest level of EphA2 protein. Thus, using 97H HCC cells, EphA2 mRNA was verified as the target of miR 26b by the luciferase reporter assay. Accordingly, a synthetic miR-26b, miR-26b mimics, was used to mimic the function of endogenous miR-26b. In 97H HCC cells transfected with miR-26b mimics or short-hairpin RNA targeting EphA2 mRNA, expression of EphA2 protein was reduced, which was associated with significantly lower proliferation rate and invasion ability and with higher apoptosis rate in response to low-dose irradiation, compared to control cells. In contrast, 97H HCC cells over-expressing EphA2 showed higher proliferation rate and invasion ability and lower apoptosis rate upon irradiation. These data suggest that miR-26b enhances the radiosensitivity of 97H HCC cells by targeting EphA2 protein. PMID- 26843136 TI - Photon upconversion: from two-photon absorption (TPA) to triplet-triplet annihilation (TTA). AB - Organic upconversion is a unique process in which low-energy light (usually NIR light) is converted to high-energy light through either the two-photon absorption (TPA) mechanism or the triplet-triplet annihilation (TTA) mechanism. Both TPA upconversion (TPA-UC) and TTA upconversion (TTA-UC) have been actively investigated in recent years due to their intriguing applications in optics, biophotonics, and solar energy utilization. Although they show some similarity (i.e., belonging to the nonlinear two-quantum process and needing focused excitation light), TPA-UC and TTA-UC are very different, such as in mechanism, characteristics involved, molecular design and potential applications. Here, we collectively reviewed these two kinds of upconversion processes and compared their respective characteristics and merits. We also present recent advances made in the areas of TPA- and TTA-UC, the remaining challenges and opportunities, with particular emphasis on molecular engineering of these two active upconversion materials. PMID- 26843135 TI - Suppression law of quantum states in a 3D photonic fast Fourier transform chip. AB - The identification of phenomena able to pinpoint quantum interference is attracting large interest. Indeed, a generalization of the Hong-Ou-Mandel effect valid for any number of photons and optical modes would represent an important leap ahead both from a fundamental perspective and for practical applications, such as certification of photonic quantum devices, whose computational speedup is expected to depend critically on multi-particle interference. Quantum distinctive features have been predicted for many particles injected into multimode interferometers implementing the Fourier transform over the optical modes. Here we develop a scalable approach for the implementation of the fast Fourier transform algorithm using three-dimensional photonic integrated interferometers, fabricated via femtosecond laser writing technique. We observe the suppression law for a large number of output states with four- and eight-mode optical circuits: the experimental results demonstrate genuine quantum interference between the injected photons, thus offering a powerful tool for diagnostic of photonic platforms. PMID- 26843138 TI - Nutritional education for management of osteodystrophy: Impact on serum phosphorus, quality of life, and malnutrition. AB - Introduction Osteodystrophy management includes dietary phosphorus restriction, which may limit protein intake, exacerbate malnutrition-inflammation syndrome and mortality among hemodialysis patients. Methods A multicenter randomized controlled trial was conducted in Lebanon, to test the hypothesis that intensive nutrition education focused on phosphorus-to-protein balance will improve patient outcomes. Six hemodialysis units were randomly assigned to the trained hospital dietitian (THD) protocol (210 patients). Six others (184 patients) were divided equally according to the patients' dialysis shifts and assigned to Dedicated Dietitian (DD) and Control protocols. Patients in the THD group received nutrition education from hospital dietitians who were trained by the study team on renal dietetics, but had limited time for hemodialysis patients. Patients in the DD group received individualized nutritional education on dietary phosphorus and protein management for 6 months (2-hour/patient/month) from study renal dietitians. Patients in the control group continued receiving routine care from hospital dietitians who had limited time for these patients and were blinded to the study. Serum phosphorus (mmol/L), malnutrition-inflammation score (MIS), health-related quality of life (HRQOL) index and length of hospital stay (LOS) were assessed at T0 (baseline), T1 (postintervention) and T2 (post6 month follow up). Findings Only the DD protocol significantly improved serum phosphorus (T0:1.78 +/- 0.5, T1:1.63 +/- 0.46, T2:1.69 +/- 0.53), 3 domains of the HRQOL and maintained MIS at T1, but this protective effect resolved at T2. The LOS significantly dropped for all groups. Discussion The presence of competent renal dietitians fully dedicated to hemodialysis units was superior over the other protocols in temporarily improving patient outcomes. PMID- 26843137 TI - Depth-dependent stratum corneum permeability in human skin in vitro. AB - The stratum corneum (SC), a permeable membrane, limits percutaneous penetration. As SC chemical and structural properties responsible for skin barrier function appear depth-related, we conducted an in vitro dermatopharmacokinetic study on intact and adhesive tape-stripped skin samples to clarify whether SC is a homogeneous barrier for chemical transport. SC concentration-thickness profiles were determined for four C-14 labeled model chemicals, panthenol, benzoic acid, paraoxon and butenafine, using the tape-stripping approach. Data analysis with the unsteady-state diffusion equation of Fick's second law permitted a chemical diffusion coefficient in SC. To evaluate the consistency of SC permeability from its surface to lower levels, the skin was tape-stripped five to 10 times to remove the upper cell layers before chemical application, such that diffusion coefficients could be determined from three SC depth levels (0, 5 and 10 tape strips). Results suggested the depth-dependency of SC permeability to panthenol, benzoic acid and butenafine; the diffusion coefficient of panthenol decreased significantly after the first five tape strips and subsequently remained consistent. A progressive increase in diffusion coefficients of benzoic acid and butenafine was observed as tape-stripping levels increased. The removal of superficial SC did not result in a significant difference in the paraoxon diffusion coefficient. For individual chemicals, a variation in the diffusion coefficient from SC surface to deeper layers agreed with the change of the diffusion coefficient over time in intact skin. Characterization of the SC properties contributing to the depth-dependent SC permeability will hopefully provide further insight to skin penetration/decontamination. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26843139 TI - Emerging halogenated flame retardants and hexabromocyclododecanes in food samples from an e-waste processing area in Vietnam. AB - This study reports concentrations of selected emerging halogenated flame retardants (HFRs) and hexabromocyclododecanes (HBCDs) in foodstuffs sourced from an e-waste processing area in Vietnam and two reference sites in Vietnam and Japan. Concentrations of all target HFRs in e-waste-impacted samples in this study exceed significantly (p < 0.05) those detected in the controls, suggesting that e-waste processing activities exert a substantial impact on local environmental contamination and human dietary exposure. Significant linear positive correlations in concentrations of syn-Dechlorane Plus (DP) and anti-DP were found between soils and those in co-located chicken samples (p < 0.05). This implies that soil is an important exposure source of DPs in chickens at our sampling sites. The estimated dietary intakes of emerging HFRs in this study were 170 and 420 ng per kg bw per day for adults and children, respectively, while daily ingestions of HBCDs were estimated to be 480 and 1500 ng per kg bw per day for adults and children, respectively. Exposure at the site monitored in this study exceeds substantially the estimates of dietary exposure to HBCDs in e-waste processing sites and non-e-waste processing areas elsewhere. PMID- 26843140 TI - Vitamin D supplementation trial in infancy: body composition effects at 3 years of age in a prospective follow-up study from Montreal. AB - BACKGROUND: The impact of vitamin D status on body composition is not well understood. OBJECTIVES: Evaluate how vitamin D supplementation in infancy affects body composition at 3 years of age. METHODS: Double-blind randomized trial of 132, 1-month-old healthy, breastfed infants randomly assigned to receive oral vitamin D3 supplements of 400, 800, 1200 or 1600 IU d-1 for 11 months. In the present analysis, 87 (66%) returned at 3 years of age. Body composition was measured using dual-energy x-ray absorptiometry and plasma 25-hydroxyvitamin D [25(OH)D] concentrations by liquid chromatography tandem mass spectrometry. RESULTS: Anthropometry, body composition, diet, activity and demographics were similar across dosage groups at 3 years. Mean 25(OH)D concentration from 1 month to 3 years was higher (P < 0.001) in the 1200 IU group than 800 and 400 IU groups. Children with 25(OH)D concentrations above 75 nmol L-1 had lower fat mass (~450 g; P = 0.049). In multiple linear regression, mean 25(OH)D was associated with lean mass percent (beta = 0.06; CI: 0.00, 0.12; P = 0.042), fat mass (beta = -11.29; CI: -22.06, -0.52; P = 0.048) and body fat percent (beta = -0.06; CI: 0.12, -0.01; P = 0.045). CONCLUSIONS: Higher vitamin D status from infancy through to 3 years of age associates with leaner body composition. PMID- 26843142 TI - Catenary nanostructures as compact Bessel beam generators. AB - Non-diffracting Bessel beams, including zero-order and high-order Bessel Beams which carry orbital angular momentum (OAM), enable a variety of important applications in optical micromanipulation, sub-diffraction imaging, high speed photonics/quantum communication, etc. The commonly used ways to create Bessel beams, including an axicon or a digital hologram written to a spatial light modulator (SLM), have great challenges to operate at the nanoscale. Here we theoretically design and experimentally demonstrate one kind of planar Bessel beam generators based on metasurfaces with analytical structures perforated in ultra-thin metallic screens. Continuous phase modulation between 0 to 2pi is realized with a single element. In addition, due to the dispersionless phase shift stemming from spin-orbit interaction, the proposed device can work in a wide wavelength range. The results may find applications in future optical communication, nanofabrication and super-resolution imaging, etc. PMID- 26843141 TI - Presymptomatic MPTP Mice Show Neurotrophic S100B/mRAGE Striatal Levels. AB - AIMS: Astrocytic S100B and receptor for advanced glycation endproducts (RAGE) have been implicated in Parkinson's disease (PD) pathogenesis through yet unclear mechanisms. This study attempted to characterize S100B/mRAGE (signaling isoform) axis in a dying-back dopaminergic (DAergic) axonopathy setting, which mimics an early event of PD pathology. METHODS: C57BL/6 mice were submitted to a chronic MPTP paradigm (20 mg/kg i.p., 2 i.d-12 h apart, 5 days/week for 2 weeks) and euthanized 7 days posttreatment to assess mRAGE cellular distribution and S100B/mRAGE density in striatum, after probing their locomotor activity (pole test and rotarod). Dopaminergic status, oxidative stress, and gliosis were also measured (HPLC-ED, WB, IHC). RESULTS: This MPTP regimen triggered increased oxidative stress (augmented HNE levels), gliosis (GS/Iba1-reactive morphology), loss of DAergic fibers (decreased tyrosine hydroxylase levels), and severe hypodopaminergia. Biochemical deficits were not translated into motor abnormalities, mimicking a presymptomatic PD period. Remarkably, striatal neurotrophic S100B/mRAGE levels and major neuronal mRAGE localization coexist with compensatory responses (3-fold increase in DA turnover), which are important to maintain normal motor function. CONCLUSION: Our findings rule out the involvement of S100B/mRAGE axis in striatal reactive gliosis, DAergic axonopathy and warrant further exploration of its neurotrophic effects in a presymptomatic compensatory PD stage, which is a fundamental period for successful implementation of therapeutic strategies. PMID- 26843144 TI - Variation in the pupil light reflex between winter and summer seasons. PMID- 26843143 TI - Plasmon-assisted trapping of nanoparticles using a silver-nanowire-embedded PMMA nanofiber. AB - The integration of surface plasmon with waveguide is a strategy for lab-on-a-chip compatible optical trapping. Here, we report a method for trapping of nanoparticles using a silver nanowire (AgNW) embedded poly(methyl methacrylate) (PMMA) nanofiber with the assistance of surface plasmon polaritons (SPPs). The nanoparticles (polystyrene, 700 nm diameter) are transported along the nanofiber and ultimately trapped at the AgNW embedded region because of the enhanced optical gradient force towards the nanofiber exerted on the nanoparticles and optical potential well generated by the excitation of SPPs. The low optical power requirement and the easy fabrication of the AgNW-embedded nanofiber with broad range of wavelength for SPPs are advantageous to the applications in optofluidics and plasmofluidics. PMID- 26843146 TI - Lumbar neuraxial anatomical changes throughout pregnancy: a longitudinal study using serial ultrasound scans. AB - This observational study was designed to investigate the anatomical changes of the lumbar spine over the course of pregnancy using serial ultrasound scans. We performed paramedian scans on 58 women at the L2-3, L3-4 and L4-5 levels; these were done at four periods of 11+0-13+6, 19+0-23+0, 28+0-32+0 and 38+0-40+0 weeks gestation. At each intervertebral level, the length of the interlaminar space, length of the visible intervertebral posterior dura and depth of the posterior dura mater from the skin were measured. The length of the interlaminar space and length of the visible intervertebral posterior dura mater were longer, and the depth of the posterior dura mater was shallower, with ascending spinal interspace. The depth of the posterior dura mater increased during pregnancy, although it plateaued between the third and fourth measurement periods. The other spinal measurements were not affected by gestation. These findings indicate that the L2-3 level is the most appropriate puncture site for epidural anaesthesia in pregnant women. Our results ought to be embraced as a departure point towards developing neuraxial insertion techniques guided or aided by ultrasound. PMID- 26843145 TI - The natural history of recent hepatitis C virus infection among blood donors and injection drug users in the country of Georgia. AB - INTRODUCTION: Hepatitis C virus (HCV) infection is a serious health problem in Georgia. METHODS: We conducted a prospective study to identify and characterize the natural history of recent HCV infection since very first days of infection. Recent HCV infection was defined as detectable plasma HCV RNA in the absence of anti-HCV antibodies. RESULTS: A total of 7600 HCV seronegative blood donors and 3600 HCV seronegative drug users were screened for recent HCV infection. Among them 7 (0.09 %) blood donors and 10 (0.28 %) drug users tested positive for HCV RNA and were classified as having recent HCV infection. Of these 17 patients 4 (23.5 %) spontaneously cleared the virus by the end of 24 week follow-up. Five clinical forms of recent HCV infection were identified during the follow-up. Four patients had symptomatic disease, including 3 patients with jaundice and other clinical symptoms (2 of them cleared virus) and 1 patient only had other symptoms without jaundice. All symptomatic patients had ALT elevation. Three distinct variants of asymptomatic disease were identified in 13 patients: 9 patients had ALT elevation and none cleared the virus; 2 patients developed chronic disease without ALT elevation; 2 patients cleared virus without anti-HCV seroconversion and without ALT elevation; this form can be described as transitory HCV viremia. CONCLUSION: Additional studies are needed to define clinical and public health implications of transitory HCV viremia. Our study suggests the need for implementing nucleic acid testing of blood donors and key populations in order to more effectively identify HCV infected persons. PMID- 26843147 TI - Upright activity within the first week after stroke is associated with better functional outcome and health-related quality of life: A Norwegian multi-site study. AB - OBJECTIVE: To assess the amount of early upright activity of patients managed in Norwegian stroke units and its association with functional outcome and health related quality of life 3 months later. DESIGN: A prospective observational multi centre study. SUBJECTS: A total of 390 acute stroke patients, mean age 76.8 years, 48.1% men, less than 14 days post-stroke, recruited from 11 Norwegian stroke units. METHODS: Time spent in different activity categories (in bed, sitting out of bed, upright) was observed with a standard method. Outcome was assessed by modified Rankin Scale (mRS), and health-related quality of life by EuroQol-5 Dimension 5 level (EQ-5D-5L) 3 months later. Ordinal logistic and linear regression analyses were used to examine the association between activity categories and mRS and EQ-5D-5L, respectively. Age, National Institute of Health Stroke Scale (NIHSS) score, premorbid mRS, sex, and hospital-site were added as covariates. RESULTS: The odds ratio (OR) (95% confidence interval (CI)) for poorer functional outcome (higher mRS) decreased as time spent in upright activities increased (OR 0.97 (95% CI 0.94-1.00)). There was also a significant positive association between time in upright activity and higher EQ-5D-5L, Beta 0.184 (95% CI 0.001- 0.008) 3 months later. CONCLUSION: This study confirms the beneficial effect of upright activity applied during hospital stay in Norwegian stroke units. PMID- 26843148 TI - Histological data in a combined phylogenetic analysis of scleractinian reef corals. AB - Scleractinian systematics have undergone rapid changes due to increased use of molecular phylogenetics and new perspectives on skeletal morphology from micromorphology and microstructure. Despite this increase in characters there are still unresolved clades in the phylogeny, indicating that more characters are needed. This study investigates a new source of morphological data within the soft tissue of Indo-Pacific scleractinian corals. Features of tissue layers, especially cnidocytes, are described in hematoxylin and eosin stained thin sections. Based on this new histological data source, a combined analysis with mitochondrial DNA and skeletal data is performed using parsimony and Bayesian analysis. Parsimony analysis yields three most-parsimonious trees similar to trees based on Bayesian analysis. Character maps are also produced that show origination of histomorphological traits at deep nodes within the phylogeny. In general, both analyses retain the previously designated families Lobophylliidae and Merulinidae, but some genera are found to be paraphyletic. Nonetheless, the combined analysis produces a highly resolved and well-supported phylogeny, which could lead to more effective use of biological conservation metrics based on evolutionary distinctiveness. These results show for the first time that inclusion of histomorphological characters improves the resolution of phylogenetic analyses of reef corals. PMID- 26843149 TI - Realization of mid-infrared graphene hyperbolic metamaterials. AB - While metal is the most common conducting constituent element in the fabrication of metamaterials, graphene provides another useful building block, that is, a truly two-dimensional conducting sheet whose conductivity can be controlled by doping. Here we report the experimental realization of a multilayer structure of alternating graphene and Al2O3 layers, a structure similar to the metal dielectric multilayers commonly used in creating visible wavelength hyperbolic metamaterials. Chemical vapour deposited graphene rather than exfoliated or epitaxial graphene is used, because layer transfer methods are easily applied in fabrication. We employ a method of doping to increase the layer conductivity, and our analysis shows that the doped chemical vapour deposited graphene has good optical properties in the mid-infrared range. We therefore design the metamaterial for mid-infrared operation; our characterization with an infrared ellipsometer demonstrates that the metamaterial experiences an optical topological transition from elliptic to hyperbolic dispersion at a wavelength of 4.5 MUm. PMID- 26843150 TI - Adaptive anisotropic gaussian filtering to reduce acquisition time in cardiac diffusion tensor imaging. AB - Diffusion tensor imaging (DTI) is used to quantify myocardial fiber orientation based on helical angles (HA). Accurate HA measurements require multiple excitations (NEX) and/or several diffusion encoding directions (DED). However, increasing NEX and/or DED increases acquisition time (TA). Therefore, in this study, we propose to reduce TA by implementing a 3D adaptive anisotropic Gaussian filter (AAGF) on the DTI data acquired from ex-vivo healthy and infarcted porcine hearts. DTI was performed on ex-vivo hearts [9-healthy, 3-myocardial infarction (MI)] with several combinations of DED and NEX. AAGF, mean (AVF) and median filters (MF) were applied on the primary eigenvectors of the diffusion tensor prior to HA estimation. The performance of AAGF was compared against AVF and MF. Root mean square error (RMSE), concordance correlation-coefficients and Bland Altman's technique was used to determine optimal combination of DED and NEX that generated the best HA maps in the least possible TA. Lastly, the effect of implementing AAGF on the infarcted porcine hearts was also investigated. RMSE in HA estimation for AAGF was lower compared to AVF or MF. Post-filtering (AAGF) fewer DED and NEX were required to achieve HA maps with similar integrity as those obtained from higher NEX and/or DED. Pathological alterations caused in HA orientation in the MI model were preserved post-filtering (AAGF). Our results demonstrate that AAGF reduces TA without affecting the integrity of the myocardial microstructure. PMID- 26843152 TI - Using growth velocity to predict child mortality. AB - BACKGROUND: Growth assessment based on the WHO child growth velocity standards can potentially be used to predict adverse health outcomes. Nevertheless, there are very few studies on growth velocity to predict mortality. OBJECTIVES: We aimed to determine the ability of various growth velocity measures to predict child death within 3 mo and to compare it with those of attained growth measures. DESIGN: Data from 5657 children <5 y old who were enrolled in a cohort study in the Democratic Republic of Congo were used. Children were measured up to 6 times in 3-mo intervals, and 246 (4.3%) children died during the study period. Generalized estimating equation (GEE) models informed the mortality risk within 3 mo for weight and length velocity z scores and 3-mo changes in midupper arm circumference (MUAC). We used receiver operating characteristic (ROC) curves to present balance in sensitivity and specificity to predict child death. RESULTS: GEE models showed that children had an exponential increase in the risk of dying with decreasing growth velocity in all 4 indexes (1.2- to 2.4-fold for every unit decrease). A length and weight velocity z score of <-3 was associated with an 11.8- and a 7.9-fold increase, respectively, in the RR of death in the subsequent 3-mo period (95% CIs: 3.9, 35.5, and 3.9, 16.2, respectively). Weight and length velocity z scores had better predictive abilities [area under the ROC curves (AUCs) of 0.67 and 0.69] than did weight-for-age (AUC: 0.57) and length-for-age (AUC: 0.52) z scores. Among wasted children (weight-for-height z score <-2), the AUC of weight velocity z scores was 0.87. Absolute MUAC performed best among the attained indexes (AUC: 0.63), but longitudinal assessment of MUAC-based indexes did not increase the predictive value. CONCLUSION: Although repeated growth measures are slightly more complex to implement, their superiority in mortality predictive abilities suggests that these could be used more for identifying children at increased risk of death. PMID- 26843151 TI - Dietary fat intake and reproductive hormone concentrations and ovulation in regularly menstruating women. AB - BACKGROUND: Emerging evidence suggests potential links between some dietary fatty acids and improved fertility, because specific fatty acids may affect prostaglandin synthesis and steroidogenesis. OBJECTIVE: The objective of this exploratory study was to evaluate associations between total and specific types of dietary fat intake and 1) hormone concentrations and 2) the risk of sporadic anovulation in a cohort of 259 regularly menstruating women in the BioCycle Study. DESIGN: Endogenous reproductive hormones were measured up to 8 times/cycle for up to 2 cycles, with visits scheduled with the use of fertility monitors. Dietary intake was assessed with up to four 24-h recalls/cycle. Linear mixed models and generalized linear models were used to evaluate the associations between dietary fatty acids and both reproductive hormone concentrations and ovulatory status. All models were adjusted for total energy intake, age, body mass index, and race. RESULTS: Relative to the lowest levels of percentage of energy from total fat, the highest tertile was associated with increased total and free testosterone concentrations (total: percentage change of 4.0%; 95% CI: 0.7%, 7.3%; free: percentage change of 4.1%; 95% CI: 0.5%, 7.7%). In particular, the percentage of energy from polyunsaturated fatty acids (PUFAs) in the highest tertile was associated with increases in total and free testosterone (total: percentage change of 3.7%; 95% CI: 0.6%, 6.8%; free: percentage change of 4.0%; 95% CI: 0.5%, 7.5%). The PUFA docosapentaenoic acid (22:5n-3) was not significantly associated with testosterone concentrations (P-trend = 0.86 in energy substitution models) but was associated with increased progesterone and a reduced risk of anovulation (highest tertile compared with the lowest tertile: RR: 0.42; 95% CI: 0.18, 0.95). Fat intakes were not associated with other reproductive hormone concentrations. CONCLUSIONS: These results indicate that total fat intake, and PUFA intake in particular, is associated with very small increases in testosterone concentrations in healthy women and that increased docosapentaenoic acid was associated with a lower risk of anovulation. PMID- 26843153 TI - Comparison of iron status 28 d after provision of antimalarial treatment with iron therapy compared with antimalarial treatment alone in Ugandan children with severe malaria. AB - BACKGROUND: The provision of iron with antimalarial treatment is the standard of care for concurrent iron deficiency and malaria. However, iron that is given during a malaria episode may not be well absorbed or used, particularly in children with severe malaria and profound inflammation. OBJECTIVES: We aimed to 1) determine baseline values of iron and inflammatory markers in children with severe malarial anemia (SMA), children with cerebral malaria (CM), and community children (CC) and 2) compare markers in iron-deficient children in each group who received 28 d of iron supplementation during antimalarial treatment with those in children who did not receive iron during treatment.. DESIGN: Seventy-nine children with CM, 77 children with SMA, and 83 CC who presented to Mulago Hospital, Kampala, Uganda, were enrolled in a 28-d iron-therapy study. Children with malaria received antimalarial treatment. All children with CM or SMA, as well as 35 CC, had zinc protoporphyrin (ZPP) concentrations >=80 MUmol/mol heme and were randomly assigned to receive a 28-d course of iron or no iron. We compared iron markers at day 0 among study groups (CM, SMA, and CC groups) and at day 28 between children in each group who were randomly assigned to receive iron or to not receive iron. RESULTS: At day 0, children with CM and SMA had greater values of C-reactive protein, ferritin, and hepcidin than those of CC. At day 28, interactions between study and treatment group were NS. Children in the no-iron compared with iron groups had similar mean values for hemoglobin (115 compared with 113 g/L, respectively; P = 0.73) and ZPP (124 compared with 124 MUmol/mol heme, respectively; P = 0.96) but had lower median ferritin [101.0 MUg/L (95% CI: 84.2, 121.0 MUg/L) compared with 152.9 MUg/L (128.8, 181.6 MUg/L), respectively; P <= 0.001] and hepcidin [45.8 ng/mL (36.8, 56.9 ng/mL) compared with 83.1 ng/mL (67.6, 102.2 ng/mL), respectively; P < 0.011]. CONCLUSIONS: Severe inflammation is a characterization of children with CM and SMA. The withholding of iron from children with severe malaria is associated with lower ferritin and hepcidin at day 28 but not a lower hemoglobin concentration. This trial was registered at clinicaltrials.gov as NCT01093989. PMID- 26843154 TI - Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial. AB - BACKGROUND: There is much speculation with regard to the potential cardioprotective benefits of equol, a microbial-derived metabolite of the isoflavone daidzein, which is produced in the large intestine after soy intake in 30% of Western populations. Although cross-sectional and retrospective data support favorable associations between the equol producer (EP) phenotype and cardiometabolic health, few studies have prospectively recruited EPs to confirm this association. OBJECTIVE: The aim was to determine whether the acute vascular benefits of isoflavones differ according to EP phenotype and subsequently investigate the effect of providing commercially produced S-(-)equol to non-EPs. DESIGN: We prospectively recruited male EPs and non-EPs (n = 14/group) at moderate cardiovascular risk into a double-blind, placebo-controlled crossover study to examine the acute effects of soy isoflavones (80-mg aglycone equivalents) on arterial stiffness [carotid-femoral pulse-wave velocity (cfPWV)], blood pressure, endothelial function (measured by using the EndoPAT 2000; Itamar Medical), and nitric oxide at baseline (0 h) and 6 and 24 h after intake. In a separate assessment, non-EPs consumed 40 mg S-(-)equol with identical vascular measurements performed 2 h after intake. RESULTS: After soy intake, cfPWV significantly improved in EPs at 24 h (cfPWV change from 0 h: isoflavone, -0.2 +/ 0.2 m/s; placebo, 0.6 +/- 0.2 m/s; P < 0.01), which was significantly associated with plasma equol concentrations (R = -0.36, P = 0.01). No vascular effects were observed in EPs at 6 h or in non-EPs at any time point. Similarly, no benefit of commercially produced S-(-)equol was observed in non-EPs despite mean plasma equol concentrations reaching 3.2 MUmol/L. CONCLUSIONS: Acute soy intake improved cfPWV in EPs, equating to an 11-12% reduced risk of cardiovascular disease if sustained. However, a single dose of commercially produced equol had no cardiovascular benefits in non-EPs. These data suggest that the EP phenotype is critical in unlocking the vascular benefits of equol in men, and long-term trials should focus on confirming the implications of EP phenotype on cardiovascular health. This trial was registered at clinicaltrials.gov as NCT01530893. PMID- 26843155 TI - Effects of maternal and child lipid-based nutrient supplements on infant development: a randomized trial in Malawi. AB - BACKGROUND: Maternal and infant undernutrition is associated with poor infant development; however, few studies have examined the impact of combined pre- and postnatal dietary supplementation on infant development. OBJECTIVE: Our objective was to determine whether provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) to mothers during pregnancy and the first 6 mo postpartum, and to children aged 6-18 mo, improves infant development in Malawi. DESIGN: We randomly assigned 869 pregnant women to receive one of the following daily: an iron and folic acid (IFA) capsule, a multiple micronutrient (MMN) capsule containing 18 micronutrients, or a 20-g sachet of SQ-LNSs containing 22 vitamins and minerals, protein, carbohydrates, essential fatty acids, and 118 kcal. Children in the lipid-based nutrient supplement (LNS) group only received SQ-LNSs from 6 to 18 mo of age. We monitored the acquisition of 11 developmental milestones monthly by maternal report; observed the attainment of 7 motor milestones at 6, 12, and 18 mo of age; and conducted a comprehensive assessment of motor, language, and socioemotional development and executive function at 18 mo of age. The primary analysis was by intention-to-treat. RESULTS: By maternal report, children in the LNS group achieved walking alone (B = 0.53; 95% CI: 0.11, 0.94; P = 0.034) and waving goodbye (B = 0.60; 95% CI: 0.12, 1.08; P = 0.040) earlier than the IFA group and standing with assistance earlier than the MMN group (B = 0.51; 95% CI: 0.12, 0.89; P = 0.029). By researcher observation, there was a trend (P = 0.052) for a greater percentage of children in the LNS group (58%) to walk alone at age 12 mo than in the IFA (49%) and MMN (49%) groups. At age 18 mo, there were no significant differences between groups in any scores. CONCLUSION: Although provision of SQ-LNSs to pregnant women and infants in Malawi may affect the age of acquisition of certain developmental milestones, it did not affect our assessments of motor, language, socioemotional, or executive function skills at 18 mo of age. This trial was registered at clinicaltrials.gov as NCT01239693. PMID- 26843156 TI - Phase angle and its determinants in healthy subjects: influence of body composition. AB - BACKGROUND: The phase angle (PA) has been used as a prognostic marker in several clinical situations. Nevertheless, its biological meaning is not completely understood. OBJECTIVE: We verified how body-composition components could explain the PA. DESIGN: The trial was a cross-sectional study involving 1442 participants (women: 58.5%; Caucasian: 40.2%) from body-composition studies. Labeled tritium dilution and total-body potassium were used to estimate total-body water (TBW) and intracellular water (ICW), respectively. Extracellular water (ECW) and the ECW:ICW ratio were estimated from the difference and the ratio of these values. Fat-free mass (FFM) and fat mass (FM) were estimated with the use of dual-energy X-ray absorptiometry, underwater weighing (UWW), and TBW. The PA was estimated with the use of a single-frequency bioelectrical impedance analysis system. Correlations between the PA and all body-composition variables were evaluated. A multivariate linear regression analysis was performed to adjust for the effects of body-composition variables on the PA variability. All analyses were performed separately by sex. RESULTS: Compared with men, women exhibited significantly larger ECW:ICW ratios and FM. The highest positive correlation was shown between the PA and FFM obtained with the use of UWW (both sexes). The highest negative correlation was shown between the PA and ECW:ICW ratios for both sexes. Age, race, height, ECW:ICW, and FFM from UWW were significant PA determinants in a multivariate linear regression model. Even after adjustment for all significant covariates, the explained PA variance was low (adjusted R(2) = 0.539 and 0.421 in men and women, respectively). The greatest impact on the total PA prediction in both men and women were age, FFM, and height. CONCLUSIONS: Age is the most significant PA predictor in men and women followed by FFM and height. The ECW:ICW contribution may explain the association of the PA observed in the clinical setting and in people who are obese. PMID- 26843157 TI - Association between alcohol consumption and the risk of incident type 2 diabetes: a systematic review and dose-response meta-analysis. AB - BACKGROUND: Previous cohort studies have shown that moderate alcohol consumption was associated with a lower risk of type 2 diabetes (T2D). However, whether these associations differ according to the characteristics of patients with T2D remains controversial. OBJECTIVE: The purpose of this study was to explore and summarize the evidence on the strength of the association between alcohol consumption and the subsequent risk of T2D by using a dose-response meta-analytic approach. DESIGN: We identified potential studies by searching the PubMed, Embase, and Cochrane Library databases up to 24 March 2015. Prospective observational studies that evaluated the relation between alcohol consumption and the risk of T2D and reported its effect estimates with 95% CIs were included. RESULTS: Analyses were based on 706,716 individuals (275,711 men and 431,005 women) from 26 studies with 31,621 T2D cases. We detected a nonlinear relation between alcohol consumption and the risk of T2D, which was identified in all cohorts (P-trend < 0.001, P nonlinearity < 0.001), in men (P-trend < 0.001, P-nonlinearity < 0.001), and in women (P-trend < 0.001, P-nonlinearity < 0.001). Compared with the minimal category of alcohol consumption, light (RR: 0.83; 95% CI: 0.73, 0.95; P = 0.005) and moderate (RR: 0.74; 95% CI: 0.67, 0.82; P < 0.001) alcohol consumption was associated with a lower risk of T2D. However, heavy alcohol consumption had little or no effect on subsequent T2D risk. Furthermore, the summary RR ratio (RRR; male to female) of the comparison between moderate alcohol consumption and the minimal alcohol categories for T2D was significantly higher, and the pooled RRR (current smoker to never smoker) of light alcohol consumption was significantly reduced. CONCLUSIONS: Light and moderate alcohol consumption was associated with a lower risk of T2D, whereas heavy alcohol consumption was not related to the risk of T2D. PMID- 26843158 TI - Noninvasive assessment of extracellular and intracellular dehydration in healthy humans using the resistance-reactance-score graph method. AB - BACKGROUND: Few dehydration assessment measures provide accurate information; most are based on reference change values and very few are diagnostically accurate from a single observation or measure. Bioelectrical impedance may lack the precision to detect common forms of dehydration in healthy individuals. Limitations in bioimpedance may be addressed by a unique resistance-reactance (RXc)-score graph method, which transforms vector components into z scores for use with any impedance analyzer in any population. OBJECTIVE: We tested whether the RXc-score graph method provides accurate single or serial assessments of dehydration when compared with gold-standard measures of total body water by using stable isotope dilution (deuterium oxide) combined with body-weight changes. DESIGN: We retrospectively analyzed data from a previous study in which 9 healthy young men participated in 3 trials: euhydration (EUH), extracellular dehydration (ED; via a diuretic), and intracellular dehydration (ID; via exercise in the heat). RESULTS: Participants lost 4-5% of their body weight during the dehydration trials; volume loss was similar between trials (ID compared with ED group: 3.5 +/- 0.8 compared with 3.0 +/- 0.6 L; P > 0.05). Despite significant losses of body water, most RXc vector scores for ED and ID groups were classified as "normal" (within the 75% population tolerance ellipse). However, directional displacement of vectors was consistent with loss of volume in both ED and ID conditions compared with the EUH condition and tended to be longer in ED than in ID conditions (P = 0.054). CONCLUSIONS: We conclude that, whereas individual RXc score graph values do not provide accurate detection of dehydration from single measurements, directional changes in vector values from serial measurements are consistent with fluid loss for both ED and ID conditions. The RXc-score graph method may therefore alert clinicians to changes in hydration state, which may bolster the interpretation of other recognized change measures of hydration. PMID- 26843160 TI - Elicitation Approaches for Withanolide Production in Hairy Root Culture of Withania somnifera (L.) Dunal. AB - Withania somnifera (L.) Dunal is a versatile medicinal plant extensively utilized for production of phytochemical drug preparations. The roots and whole plants are traditionally used in Ayurveda, Unani, and Siddha medicines, as well as in homeopathy. Several studies provide evidence for an array of pharmaceutical properties due to the presence of steroidal lactones named "withanolides." A number of research groups have focused their attention on the effects of biotic and abiotic elicitors on withanolide production using cultures of adventitious roots, cell suspensions, shoot suspensions, and hairy roots in large-scale bioreactor for producing withanolides. This chapter explains the detailed procedures for induction and establishment of hairy roots from leaf explants of W. somnifera, proliferation and multiplication of hairy root cultures, estimation of withanolide productivity upon elicitation with salicylic acid and methyl jasmonate, and quantification of major withanolides by HPLC. The protocol herein described could be implemented for large-scale cultivation of hairy root biomass to improve withanolide production. PMID- 26843159 TI - Bidirectional association between parental child-feeding practices and body mass index at 4 and 7 y of age. AB - BACKGROUND: Evidence of the association between parental child-feeding practices and the child's body mass index (BMI) is controversial, and bidirectional effects have been poorly studied. OBJECTIVE: We aimed to examine bidirectional associations between parental child-feeding practices and BMI at 4 and 7 y of age. DESIGN: This study included 3708 singleton children from the Generation XXI birth cohort with data on parental child-feeding practices and BMI at 4 and 7 y old. Feeding practices were assessed through a self-administered questionnaire by combining the Child Feeding Questionnaire and the Overt/Covert Control scale and then adapting it to Portuguese preschool children. Weight and height were measured according to standardized procedures, and age- and sex-specific BMI z scores were computed based on the WHO Growth References. Linear regression models were used to estimate the bidirectional associations between each practice and BMI z score. Crosslagged analyses were performed to compare the directions of those associations (the mean score of each practice and BMI z score at both ages were standardized to enable effect size comparisons). RESULTS: After adjustments, pressure to eat and overt control at 4 y of age were associated with a lower BMI z score 3 y later (beta: -0.05; 95% CI: -0.08, -0.03 and beta: -0.05; 95% CI: 0.09, -0.01, respectively). Regarding the opposite direction of association, a higher BMI z score at 4 y of age was significantly associated with higher levels of restriction and covert control at 7 y of age (beta: 0.06; 95% CI: 0.03, 0.08 and beta: 0.06; 95% CI: 0.04, 0.08, respectively) and with lower levels of pressure to eat (beta: -0.17; 95% CI: -0.20, -0.15). The only bidirectional practice, pressure to eat, was more strongly influenced by the BMI z score than the reverse (betastandardized: -0.17 compared with betastandardized: -0.04; likelihood ratio test: P < 0.001). CONCLUSIONS: We found that parents both respond to and influence the child's weight; thus, this child-parent interaction should be considered in future research. PMID- 26843161 TI - Stimulant Paste Preparation and Bark Streak Tapping Technique for Pine Oleoresin Extraction. AB - Tapping technique comprises the extraction of pine oleoresin, a non-wood forest product consisting of a complex mixture of mono, sesqui, and diterpenes biosynthesized and exuded as a defense response to wounding. Oleoresin is used to produce gum rosin, turpentine, and their multiple derivatives. Oleoresin yield and quality are objects of interest in pine tree biotechnology, both in terms of environmental and genetic control. Monitoring these parameters in individual trees grown in the field provides a means to examine the control of terpene production in resin canals, as well as the identification of genetic-based differences in resinosis. A typical method of tapping involves the removal of bark and application of a chemical stimulant on the wounded area. Here we describe the methods for preparing the resin-stimulant paste with different adjuvants, as well as the bark streaking process in adult pine trees. PMID- 26843162 TI - A Modified Protocol for High-Quality RNA Extraction from Oleoresin-Producing Adult Pines. AB - RNA extraction resulting in good yields and quality is a fundamental step for the analyses of transcriptomes through high-throughput sequencing technologies, microarray, and also northern blots, RT-PCR, and RTqPCR. Even though many specific protocols designed for plants with high content of secondary metabolites have been developed, these are often expensive, time consuming, and not suitable for a wide range of tissues. Here we present a modification of the method previously described using the commercially available ConcertTM Plant RNA Reagent (Invitrogen) buffer for field-grown adult pine trees with high oleoresin content. PMID- 26843163 TI - Collection of Apoplastic Fluids from Arabidopsis thaliana Leaves. AB - The leaf apoplast comprises the extracellular continuum outside cell membranes. A broad range of processes take place in the apoplast, including intercellular signaling, metabolite transport, and plant-microbe interactions. To study these processes, it is essential to analyze the metabolite content in apoplastic fluids. Due to the fragile nature of leaf tissues, it is a challenge to obtain apoplastic fluids from leaves. Here, methods to collect apoplastic washing fluid and guttation fluid from Arabidopsis thaliana leaves are described. PMID- 26843164 TI - From Plant Extract to a cDNA Encoding a Glucosyltransferase Candidate: Proteomics and Transcriptomics as Tools to Help Elucidate Saponin Biosynthesis in Centella asiatica. AB - Centella asiatica (L.) Urban (Apiaceae), a small annual plant that grows in India, Sri Lanka, Malaysia, and other parts of Asia, is well-known as a medicinal herb with a long history of therapeutic uses. The bioactive compounds present in C. asiatica leaves include ursane-type triterpene sapogenins and saponins-asiatic acid, madecassic acid, asiaticoside, and madecassoside. Various bioactivities have been shown for these compounds, although most of the steps in the biosynthesis of triterpene saponins, including glycosylation, remain uncharacterized at the molecular level. This chapter describes an approach that integrates partial enzyme purification, proteomics methods, and transcriptomics, with the aim of reducing the number of cDNA candidates encoding for a glucosyltransferase involved in saponin biosynthesis and facilitating the elucidation of the pathway in this medicinal plant. PMID- 26843165 TI - Production of Recombinant Caffeine Synthase from Guarana (Paullinia cupana var. sorbilis) in Escherichia coli. AB - Caffeine synthase (CS) is a methyltransferase responsible for the last two steps of the caffeine biosynthesis pathway in plants. CS is able to convert 7 methylxanthine to theobromine (3,7-dimethylxanthine) and theobromine to caffeine (1,3,7-trimethylxanthine) using S-adenosyl-L-methionine as the methyl donor in both reactions. The production of a recombinant protein is an important tool for the characterization of enzymes, particularly when the enzyme has affinity for different substrates. Guarana has the highest caffeine content among more than a hundred plant species that contain this alkaloid. Different from other plants, in which CS has a higher affinity for paraxanthine (1,7-dimethylxanthine), caffeine synthase from guarana (PcCS) has a higher affinity for theobromine. Here, we describe a method to produce a recombinant caffeine synthase from guarana in Escherichia coli and its purification by affinity chromatography. The recombinant protein retains activity and can be used in enzymatic assays and other biochemical characterization studies. PMID- 26843166 TI - Heterologous Expression and Characterization of Mimosinase from Leucaena leucocephala. AB - Heterologous expression of eukaryotic genes in bacterial system is an important method in synthetic biology to characterize proteins. It is a widely used method, which can be sometimes quite challenging, as a number of factors that act along the path of expression of a transgene to mRNA, and mRNA to protein, can potentially affect the expression of a transgene in a heterologous system. Here, we describe a method for successful cloning and expression of mimosinase-encoding gene from Leucaena leucocephala (leucaena) in E. coli as the heterologous host. Mimosinase is an important enzyme especially in the context of metabolic engineering of plant secondary metabolite as it catalyzes the degradation of mimosine, which is a toxic secondary metabolite found in all Leucaena and Mimosa species. We also describe the methods used for characterization of the recombinant mimosinase. PMID- 26843167 TI - Production of Aromatic Plant Terpenoids in Recombinant Baker's Yeast. AB - Plant terpenoids are high-value compounds broadly applied as food additives or fragrances in perfumes and cosmetics. Their biotechnological production in yeast offers an attractive alternative to extraction from plants. Here, we provide two optimized protocols for the production of the plant terpenoid trans-nootkatol with recombinant S. cerevisiae by either (I) converting externally added (+) valencene with resting cells or (II) cultivating engineered self-sufficient production strains. By synthesis of the hydrophobic compounds in self-sufficient production cells, phase transfer issues can be avoided and the highly volatile products can be enriched in and easily purified from n-dodecane, which is added to the cell broth as second phase. PMID- 26843168 TI - Purification of a Recombinant Polyhistidine-Tagged Glucosyltransferase Using Immobilized Metal-Affinity Chromatography (IMAC). AB - Short peptide tags genetically fused to recombinant proteins have been widely used to facilitate detection or purification without the need to develop specific procedures. In general, an ideal affinity tag would allow the efficient purification of tagged proteins in high yield, without affecting its function. Here, we describe the purification steps to purify a recombinant polyhistidine tagged glucosyltransferase from Centella asiatica using immobilized metal affinity chromatography. PMID- 26843169 TI - A Western Blot Protocol for Detection of Proteins Heterologously Expressed in Xenopus laevis Oocytes. AB - Oocytes of the African clawed frog, Xenopus laevis, are often used for expression and biochemical characterization of transporter proteins as the oocytes are particularly suitable for uptake assays and electrophysiological recordings. Assessment of the expression level of expressed transporters at the individual oocyte level is often desirable when comparing properties of wild type and mutant transporters. However, a large content of yolk platelets in the oocyte cytoplasm makes this a challenging task. Here we report a method for fast and easy, semiquantitative Western blot analysis of proteins heterologously expressed in Xenopus oocytes. PMID- 26843170 TI - Laser Capture Microdissection: Avoiding Bias in Analysis by Selecting Just What Matters. AB - Laser capture microdissection (LCM) is a powerful technique for harvesting specific cells from a heterogeneous population. As each cell and tissue has its unique genetic, proteomic, and metabolic profile, the use of homogeneous samples is important for a better understanding of complex processes in both animal and plant systems. In case of plants, LCM is very suitable as the highly regular tissue organization and stable cell walls from these organisms enable visual identification of various cell types without staining of tissue sections, which can prevent some downstream analysis. Considering the applicability of LCM to any plant species, here we provide a step-by-step protocol for selecting specific cells or tissues through this technology. PMID- 26843171 TI - Analytical and Fluorimetric Methods for the Characterization of the Transmembrane Transport of Specialized Metabolites in Plants. AB - The characterization of membrane transport of specialized metabolites is essential to understand their metabolic fluxes and to implement metabolic engineering strategies towards the production of increased levels of these valuable metabolites. Here, we describe a set of procedures to isolate tonoplast membranes, to check their purity and functionality, and to characterize their transport properties. Transport is assayed directly by HPLC analysis and quantification of the metabolites actively accumulated in the vesicles, and indirectly using the pH sensitive fluorescent probe ACMA (9-amino-6- chloro-2 methoxyacridine), when a proton antiport is involved. PMID- 26843172 TI - Protoplast Transformation as a Plant-Transferable Transient Expression System. AB - The direct uptake of DNA by naked plant cells (protoplasts) provides an expression system of exception for the quickly growing research in non-model plants, fuelled by the power of next-generation sequencing to identify novel candidate genes. Here, we describe a simple and effective method for isolation and transformation of protoplasts, and illustrate its application to several plant materials. PMID- 26843173 TI - Design, Construction, and Validation of Artificial MicroRNA Vectors Using Agrobacterium-Mediated Transient Expression System. AB - Artificial microRNA (amiRNA) technology utilizes microRNA (miRNA) biogenesis pathway to produce artificially selected small RNAs using miRNA gene backbone. It provides a feasible strategy for inducing loss of gene function, and has been applied in functional genomics study, improvement of crop quality and plant virus disease resistance. A big challenge in amiRNA applications is the unpredictability of silencing efficacy of the designed amiRNAs and not all constructed amiRNA candidates would be expressed effectively in plant cells. We and others found that high efficiency and specificity in RNA silencing can be achieved by designing amiRNAs with perfect or almost perfect sequence complementarity to their targets. In addition, we recently demonstrated that Agrobacterium-mediated transient expression system can be used to validate amiRNA constructs, which provides a simple, rapid and effective method to select highly expressible amiRNA candidates for stable genetic transformation. Here, we describe the methods for design of amiRNA candidates with perfect or almost perfect base-pairing to the target gene or gene groups, incorporation of amiRNA candidates in miR168a gene backbone by one step inverse PCR amplification, construction of plant amiRNA expression vectors, and assay of transient expression of amiRNAs in Nicotiana benthamiana through agro-infiltration, small RNA extraction, and amiRNA Northern blot. PMID- 26843174 TI - Knockdown of Polyphenol Oxidase Gene Expression in Potato (Solanum tuberosum L.) with Artificial MicroRNAs. AB - It is of great importance and interest to develop crop varieties with low polyphenol oxidase (PPO) activity for the food industry because PPO-mediated oxidative browning is a main cause of post-harvest deterioration and quality loss of fresh produce and processed foods. We recently demonstrated that potato tubers with reduced browning phenotypes can be produced by inhibition of the expression of several PPO gene isoforms using artificial microRNA (amiRNA) technology. The approach introduces a single type of 21-nucleotide RNA population to guide silencing of the PPO gene transcripts in potato tissues. Some advantages of the technology are: small RNA molecules are genetically transformed, off-target gene silencing can be avoided or minimized at the stage of amiRNA designs, and accuracy and efficiency of the processes can be detected at every step using molecular biological techniques. Here we describe the methods for transformation and regeneration of potatoes with amiRNA vectors, detection of the expression of amiRNAs, identification of the cleaved product of the target gene transcripts, and assay of the expression level of PPO gene isoforms in potatoes. PMID- 26843175 TI - Clonal Complex 17 Group B Streptococcus strains causing invasive disease in neonates and adults originate from the same genetic pool. AB - A significant proportion of group B Streptococcus (GBS) neonatal disease, particularly late-onset disease, is associated with strains of serotype III, clonal complex (CC) 17. CC17 strains also cause invasive infections in adults. Little is known about the phylogenetic relationships of isolates recovered from neonatal and adult CC17 invasive infections. We performed whole-genome-based phylogenetic analysis of 93 temporally and geographically matched CC17 strains isolated from both neonatal and adult invasive infections in the metropolitan region of Toronto/Peel, Canada. We also mined the whole-genome data to reveal mobile genetic elements carrying antimicrobial resistance genes. We discovered that CC17 GBS strains causing neonatal and adult invasive disease are interspersed and cluster tightly in a phylogenetic tree, signifying that they are derived from the same genetic pool. We identified limited variation due to recombination in the core CC17 genome. We describe that loss of Pilus Island 1 and acquisition of different mobile genetic elements carrying determinants of antimicrobial resistance contribute to CC17 genetic diversity. Acquisition of some of these mobile genetic elements appears to correlate with clonal expansion of the strains that possess them. Our results provide a genome-wide portrait of the population structure and evolution of a major disease-causing clone of an opportunistic pathogen. PMID- 26843176 TI - Treatment of idiopathic pulmonary fibrosis: a network meta-analysis. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with high morbidity and mortality. Effective treatments for IPF are limited. Several recent studies have investigated novel therapeutic agents for IPF, but very few have addressed their comparative benefits and harms. METHODS: We performed a Bayesian network meta-analysis (NMA) to assess the effects of different treatments for IPF on mortality and serious adverse events (SAEs). We searched MEDLINE and EMBASE for randomized controlled trials (RCTs) up to August 2015. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach served to assess the certainty in the evidence of direct and indirect estimates. We calculated the surface under the cumulative ranking curve (SUCRA) for each treatment. We included parallel group RCTs, including factorial designs, but excluded quasi-randomized and cross-over trials. Studies were only included if they involved adult (>=18 years of age) patients with IPF as defined by the 2011 criteria and examined one of the 10 interventions of interest (ambrisentan, bosentan, imatinib, macitentan, N-acetylcysteine, nintedanib, pirfenidone, sildenafil, prednisone/azathioprine/N-acetylcysteine triple therapy, and vitamin K antagonist). RESULTS: A total of 19 RCTs (5,694 patients) comparing 10 different interventions with placebo and an average follow-up period of 1 year fulfilled the inclusion criteria. SUCRA analysis suggests nintedanib, pirfenidone, and sildenafil are the three treatments with the highest probability of reducing mortality in IPF. Indirect comparison showed no significant difference in mortality between pirfenidone and nintedanib (NMA OR, 1.05; 95% CrI, 0.45-2.78, moderate certainty of evidence), pirenidone and sildenafil (NMA OR, 2.26; 95% CrI, 0.44-13.17, low certainty of evidence), or nintedanib and sildenafil (NMA OR 2.40; 95% CrI, 0.47-14.66, low certainty of evidence). Sildenafil, pirfenidone, and nintedanib were ranked second, fourth, and sixth out of 10 for SAEs. CONCLUSION: In the absence of direct comparisons between treatment interventions, this NMA suggests that treatment with nintedanib, pirfenidone, and sildenafil extends survival in patients with IPF. The SAEs of these agents are similar to the other interventions and include mostly dermatologic and gastrointestinal manifestations. Head-to-head comparisons need to confirm these findings. PMID- 26843177 TI - Decreased expression of methylene tetrahydrofolate reductase (MTHFR) gene in patients with rheumatoid arthritis. AB - OBJECTIVES: Impairment of methylene tetrahydrofolate reductase (MTHFR), a key enzyme in the folate metabolism, results in an elevated plasma level of homocysteine, considered an independent risk factor for cardiovascular (CV) disease. Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased risk of CV death. Polymorphisms in the MTHFR gene increase the frequency of CV disease in RA. The aim of this study was to determine the expression of MTHFR gene in patients with RA, with and without ischaemic heart disease (IHD). METHODS: Relative expression of MTHFR gene and beta-actin and GAPDH as housekeeping genes was quantified by quantitative real-time polymerase chain reaction. It was analysed by the comparative Ct (threshold cycle) method in peripheral blood from 26 Spanish patients with RA (12 with IHD and 14 without IHD) and 10 healthy controls. MTHFR expression level in RA patients was also assessed according to disease activity, rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies status. RESULTS: MTHFR expression was significantly reduced in patients with RA compared to controls (fold change = 0.85, p=0.029). It was especially true for RA patients with IHD (fold change= 0.79, p=0.021). However, no statistically significant relationship between MTHFR expression level in patients with RA and DAS28 CRP, DAS28 ESR, RF and anti-CCP status was observed. CONCLUSIONS: Patients with RA, in particular those with IHD, show a decreased expression of the MTHFR gene. This may support a potential implication of the transcriptional regulation of MTHFR in the pathogenesis of RA. PMID- 26843179 TI - Relationship between functional connectivity and motor function assessment in stroke patients with hemiplegia: a resting-state functional MRI study. AB - INTRODUCTION: Resting-state functional magnetic resonance imaging (fMRI) has been used to examine the brain mechanisms of stroke patients with hemiplegia, but the relationship between functional connectivity (FC) and treatment-induced motor function recovery has not yet been fully investigated. This study aimed to identify the brain FC changes in stroke patients and study the relationship between FC and motor function assessment using the resting-state fMRI. METHODS: Seventeen stroke patients with hemiplegia and fifteen healthy control subjects (HCSs) were recruited in this study. We compared the FC between the ipsilesional primary motor cortex (M1) and the whole brain of the patients with the FC of the HCSs and studied the FC changes in the patients before and after conventional rehabilitation and motor imagery therapy. Additionally, correlations between the FC change and motor function of the patients were studied. RESULTS: Compared to the HCSs, the FC in the patient group was significantly increased between the ipsilesional M1 and the ipsilesional inferior parietal cortex, frontal gyrus, supplementary motor area (SMA), and contralesional angular and decreased between the ipsilesional M1 and bilateral M1. After the treatment, the FC between the ipsilesional M1 and contralesional M1 increased while the FC between the ipsilesional M1 and ipsilesional SMA and paracentral lobule decreased. A statistically significant correlation was found between the FC change in the bilateral M1 and the Fugl-Meyer assessment (FMA) score change. CONCLUSION: Our results revealed an abnormal motor network after stroke and suggested that the FC could serve as a biomarker of motor function recovery in stroke patients with hemiplegia. PMID- 26843182 TI - The Role of Interpersonal Conflict as a Determinant of Firearm-Related Homicide Suicides at Different Ages. AB - Although firearm-related homicide-suicides and firearm-related suicides are tragic and catastrophic events, there is increasing evidence that the two events have different precipitants and that understanding these precipitants may help prevention efforts. We aimed to assess the role of interpersonal conflict (IPC) and recent crises in firearm-related homicide-suicides as compared with firearm related suicides alone. We also assessed whether these differences were consistent across young and old perpetrators. Using an unmatched case-control study, we compared firearm-related homicide-suicides andsuicides alone from 2003 to 2011 in the National Violent Death Registry data to assess the risk associated with IPC and crisis. Survival analysis was performed to compare time-to-incident of homicide-suicide versus suicide only. We derived odds ratios (ORs) and 95% confidence intervals (95%CI) due to IPC and recent crisis from mixed logistic regression models. Stratified analysis by age on the effect of IPC and recent crisis, and type of incident was also performed. After adjusting for relevant covariates, homicide-suicides were more likely than suicide alone following IPC (OR = 20.6, 95%CI = [16.6, 25.7]) and recent crisis (OR = 14.5, 95%CI = [12.4, 16.9]). The risk of firearm homicide-suicide compared with suicide associated with IPC was twice greater among those >30 years compared with those <=30 years ( p-interaction = .033), and no differential by age associated with recent crisis ( p-interaction = .64). IPC and recent crisis are risk factors for committing homicide-suicides compared with suicides alone, with the risk doubly greater among older than younger perpetrators. PMID- 26843180 TI - Evidence for Noncanonical Neurotransmitter Activation: Norepinephrine as a Dopamine D2-Like Receptor Agonist. AB - The Galphai/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression patterns prompts the question of a possible noncanonical action by norepinephrine. In fact, previous studies have suggested that norepinephrine can functionally interact with D4R. To our knowledge, significant interactions between norepinephrine and D2R or D3R receptors have not been demonstrated. By using radioligand binding and bioluminescent resonance energy transfer (BRET) assays in transfected cells, the present study attempted a careful comparison between dopamine and norepinephrine in their possible activation of all D2-like receptors, including the two D2R isoforms and the most common D4R polymorphic variants. Functional BRET assays included activation of G proteins with all Galphai/o subunits, adenylyl cyclase inhibition, and beta arrestin recruitment. Norepinephrine acted as a potent agonist for all D2-like receptor subtypes, with the general rank order of potency of D3R > D4R >= D2SR >= D2L. However, for both dopamine and norepinephrine, differences depended on the Galphai/o protein subunit involved. The most striking differences were observed with Galphai2, where the rank order of potencies for both dopamine and norepinephrine were D4R > D2SR = D2LR >> D3R. Furthermore the results do not support the existence of differences in the ability of dopamine and norepinephrine to activate different human D4R variants. The potency of norepinephrine for adrenergic alpha2A receptor was only about 20-fold higher compared with D3R and D4R across the three functional assays. PMID- 26843181 TI - Characterisation of CASPR2 deficiency disorder--a syndrome involving autism, epilepsy and language impairment. AB - BACKGROUND: Heterozygous mutations in CNTNAP2 have been identified in patients with a range of complex phenotypes including intellectual disability, autism and schizophrenia. However heterozygous CNTNAP2 mutations are also found in the normal population. Conversely, homozygous mutations are rare in patient populations and have not been found in any unaffected individuals. CASE PRESENTATION: We describe a consanguineous family carrying a deletion in CNTNAP2 predicted to abolish function of its protein product, CASPR2. Homozygous family members display epilepsy, facial dysmorphisms, severe intellectual disability and impaired language. We compared these patients with previously reported individuals carrying homozygous mutations in CNTNAP2 and identified a highly recognisable phenotype. CONCLUSIONS: We propose that CASPR2 loss produces a syndrome involving early-onset refractory epilepsy, intellectual disability, language impairment and autistic features that can be recognized as CASPR2 deficiency disorder. Further screening for homozygous patients meeting these criteria, together with detailed phenotypic and molecular investigations will be crucial for understanding the contribution of CNTNAP2 to normal and disrupted development. PMID- 26843183 TI - Sibling Violence and Children Hospitalized for Serious Mental and Behavioral Health Problems. AB - Violence between siblings is prevalent, can have long-lasting negative effects, and yet it is often dismissed as normal. This study explores sibling violence (SV) documented in medical records of children hospitalized in a psychiatric hospital. Retrospective chart review was conducted of all medical records of children ages 5 years to 12 years, living with a sibling in the home, admitted during the 2007 calendar year to a northwestern psychiatric hospital that serves a five state area ( N = 135). Using a data collection tool, quantitative and qualitative data were extracted from the charts, and descriptive statistical analysis was used to identify patterns and trends. The records showed that 103 (76%) of the 135 patients perpetrated SV and 30 (22%) were victims of SV. Many of the patients perpetrating SV were also violent toward themselves and toward peers, mothers, and teachers. The majority of patients did not have a psychiatric diagnosis that included violent behavior as a criterion and most of the patients had one or more past adverse experiences. Findings suggest that children hospitalized with psychiatric problems should be screened for SV perpetration and victimization, that health care staff and parents should be educated about SV, and that further research is needed to better understand what constitutes SV, the context within which it occurs, and effects of non-protection by parents. PMID- 26843184 TI - Khaya grandifoliola C.DC: a potential source of active ingredients against hepatitis C virus in vitro. AB - In this study, we examined the antiviral properties of Khaya grandifoliola C.DC (Meliaceae) on the hepatitis C virus (HCV) life cycle in vitro and identified some of the chemical constituents contained in the fraction with the most antiviral activity. Dried bark powder was extracted by maceration in a methylene chloride/methanol (MCM) system (50:50; v/v) and separated on silica gel by flash chromatography. Infection and replication rates in Huh-7 cells were investigated by luciferase reporter assay and indirect immunofluorescence assay using subgenomic replicons, HCV pseudotyped particles, and cell-culture-derived HCV (HCVcc), respectively. Cell viability was assessed by MTT assay, and cellular gene expression was analysed by qRT-PCR. The chemical composition of the fraction with the most antiviral activity was analysed by coupled gas chromatography and mass spectrometry (GC-MS). Five fractions of different polarities (F0-F100) were obtained from the MCM extract. One fraction (KgF25) showed the strongest antiviral effect on LucUbiNeoET replicons at nontoxic concentrations. Tested at 100 ug/mL, KgF25 had a high inhibitory effect on HCV replication, comparable to that of 0.01 uM daclatasvir or 1 uM telaprevir. This fraction also inhibited HCVcc infection by mostly targeting the entry step. KgF25 inhibited HCV entry in a pan-genotypic manner by directly inactivating free viral particles. Its antiviral effects were mediated by the transcriptional upregulation of the haem oxygenase-1 gene and interferon antiviral response. Three constituents, namely, benzene, 1,1'-(oxydiethylidene)bis (1), carbamic acid, (4-methylphenyl)-, 1 phenyl (2), and 6-phenyl, 4-(1'-oxyethylphenyl) hexene (3), were identified from the active fraction KgF25 by GC-MS. Khaya grandifoliola contains ingredients capable of acting on different steps of the HCV life cycle. PMID- 26843185 TI - Population structure in Atlantic cod in the eastern North Sea-Skagerrak-Kattegat: early life stage dispersal and adult migration. AB - BACKGROUND: In marine fish species, where pelagic egg and larvae drift with ocean currents, population structure has been suggested to be maintained by larval retention due to hydrographic structuring and by homing of adult fish to natal areas. Whilst natal homing of adults has been demonstrated for anadromous and coral reef fishes, there are few documented examples of philopatric migration in temperate marine fish species. RESULTS: Here, we demonstrate temporally stable genetic differentiation among spawning populations of Atlantic cod (Gadus morhua L.), and present genetic and behavioural evidence for larval drift and philopatric migration in the eastern North Sea-Skagerrak-Kattegat area. We show that juvenile cod collected in the eastern Skagerrak and central Kattegat are genetically similar to cod from offshore spawning areas in the eastern North Sea. Genetic assignment of individual 2-5 year old fish indicates that cod residing at, or migrating towards, spawning areas in Kattegat and the North Sea display philopatric behaviours. CONCLUSIONS: Together these findings suggest a loop between spawning, larval drift and adult return-migrations to spawning areas and underlines that both oceanographic processes and migratory behaviour in the adult phase may be important for stock separation and integrity in marine temperate fishes such as Atlantic cod. PMID- 26843187 TI - Erratum for the Research Article: "RANKL blockade prevents and treats aggressive osteosarcomas" by Y. Chen, M. A. Di Grappa, S. D. Molyneux, T. D. McKee, P. Waterhouse, J. M. Penninger, R. Khokha. PMID- 26843186 TI - Long-term Cognitive Trajectories and Mortality in Older Women. AB - BACKGROUND: Few studies have examined whether change in cognition is linked to mortality. This study examined the relationship between cognitive trajectories in older age and risk of death. METHODS: We studied community-dwelling, nondemented women aged 65+ (mean age = 71) enrolled in a prospective study of aging and followed up to 25 years. A modified Mini-Mental State Examination (mMMSE) and Trail Making Task Part B (TMTB) were administered at multiple visits during follow-up. We examined the association between cognitive trajectories (analyzed by quintiles) from baseline to age 80 (n = 7,477 for mMMSE and n = 6,503 for TMTB) and all-cause mortality after age 80 using Cox regression models, both unadjusted and adjusted for education, physical activity, alcohol, depression score, current smoking and history of hypertension and diabetes. Cause of death was determined from death certificates, classified as cardiovascular, cancer and other. RESULTS: Women with greater rate of decline were older, less educated, less physically active, had higher depression score and were more likely to have a history of hypertension and diabetes (all p < .01). Participants with the greatest decline (quintile 1) had an increased risk of death (mMMSE hazard ratio [HR] = 1.28; TMTB HR = 1.43] and those with the least decline (quintile 5) had a decreased risk of death (mMMSE HR = 0.73; TMTB HR = 0.61) compared with intermediate decliners (quintiles 2-4). Cognitive trajectories were associated with cardiovascular mortality and other causes of death, but not cancer deaths. CONCLUSIONS: Our study suggests that greater decline in general cognition or executive function is associated with higher rates of mortality in oldest-old women. PMID- 26843188 TI - Perspectives from man's best friend: National Academy of Medicine's Workshop on Comparative Oncology. PMID- 26843189 TI - MM-151 overcomes acquired resistance to cetuximab and panitumumab in colorectal cancers harboring EGFR extracellular domain mutations. AB - The anti-epidermal growth factor receptor (EGFR) antibodies cetuximab and panitumumab are used to treat RAS wild-type colorectal cancers (CRCs), but their efficacy is limited by the emergence of acquired drug resistance. After EGFR blockade, about 20% of CRCs develop mutations in the EGFR extracellular domain (ECD) that impair antibody binding and are associated with clinical relapse. We hypothesized that EGFR ECD-resistant variants could be targeted by the recently developed oligoclonal antibody MM-151 that binds multiple regions of the EGFR ECD. MM-151 inhibits EGFR signaling and cell growth in preclinical models, including patient-derived cells carrying mutant EGFR. Upon MM-151 treatment, EGFR ECD mutations decline in circulating cell-free tumor DNA (ctDNA) of CRC patients who previously developed resistance to EGFR blockade. These data provide molecular rationale for the clinical use of MM-151 in patients who become resistant to cetuximab or panitumumab as a result of EGFR ECD mutations. PMID- 26843190 TI - Mathematical modeling of herpes simplex virus-2 suppression with pritelivir predicts trial outcomes. AB - Pharmacokinetic and pharmacodynamic models estimate the potency of antiviral agents but do not capture viral and immunologic factors that drive the natural dynamics of infection. We designed a mathematical model that synthesizes pharmacokinetics, pharmacodynamics, and viral pathogenesis concepts to simulate the activity of pritelivir, a DNA helicase-primase inhibitor that targets herpes simplex virus. Our simulations recapitulate detailed viral kinetic shedding features in five dosage arms of a phase 2 clinical trial. We identify that in vitro estimates of median effective concentration (EC50) are lower than in vivo values for the drug. Nevertheless, pritelivir potently decreases shedding at appropriate doses based on its mode of action and long half-life. Although pritelivir directly inhibits replication in epithelial cells, our model indicates that pritelivir also indirectly limits downstream viral spread from neurons to genital keratinocytes, within genital ulcers, and from ulcer to new mucosal sites of infection. We validate our model based on its ability to predict outcomes in a subsequent trial with a higher dose. The model can therefore be used to optimize dose selection in clinical practice. PMID- 26843191 TI - Timing of expression of the core clock gene Bmal1 influences its effects on aging and survival. AB - The absence of Bmal1, a core clock gene, results in a loss of circadian rhythms, an acceleration of aging, and a shortened life span in mice. To address the importance of circadian rhythms in the aging process, we generated conditional Bmal1 knockout mice that lacked the BMAL1 protein during adult life and found that wild-type circadian variations in wheel-running activity, heart rate, and blood pressure were abolished. Ocular abnormalities and brain astrogliosis were conserved irrespective of the timing of Bmal1 deletion. However, life span, fertility, body weight, blood glucose levels, and age-dependent arthropathy, which are altered in standard Bmal1 knockout mice, remained unaltered, whereas atherosclerosis and hair growth improved, in the conditional adult-life Bmal1 knockout mice, despite abolition of clock function. Hepatic RNA-Seq revealed that expression of oscillatory genes was dampened in the adult-life Bmal1 knockout mice, whereas overall gene expression was largely unchanged. Thus, many phenotypes in conventional Bmal1 knockout mice, hitherto attributed to disruption of circadian rhythms, reflect the loss of properties of BMAL1 that are independent of its role in the clock. These findings prompt reevaluation of the systemic consequences of disruption of the molecular clock. PMID- 26843192 TI - Paenibacillus periandrae sp. nov., isolated from nodules of Periandra mediterranea. AB - A bacterial strain designated PM10T was isolated from root nodules of Periandra mediterranea in Brazil. Phylogenetic analyses based on 16S rRNA gene sequences placed the isolate in the genus Paenibacillus with its closest relatives being Paenibacillus vulneris CCUG 53270T and Paenibacillus yunnanensis YN2T with 95.6 and 95.9% 16S rRNA gene sequence similarity, respectively. The isolate was a Gram stain-variable, motile, sporulating rod that was catalase-negative and oxidase positive. Caseinase was positive, amylase was weakly positive and gelatinase was negative. Growth was supported by many carbohydrates and organic acids as carbon sources. MK-7 was the only menaquinone detected and anteiso-C15 : 0 was the major fatty acid. Major polar lipids were diphosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol and two unidentified lipids. meso-Diaminopimelic acid was detected in the peptidoglycan. The DNA G+C content was 52.9 mol%. Phylogenetic, chemotaxonomic and phenotypic analyses showed that strain PM10T should be considered representative of a novel species of the genus Paenibacillus, for which the name Paenibacillus periandrae sp. nov. is proposed. The type strain is PM10T (=LMG 28691T=CECT 8827T). PMID- 26843193 TI - The Association Between Psychiatric Disorders and Frequent Indoor Tanning. PMID- 26843194 TI - Predictive factors of long-term survival in the octogenarian undergoing surgical aortic valve replacement: 12-year single-centre follow-up. AB - The improvement of life expectancy created more surgical candidates with severe symptomatic aortic stenosis and age >80. Therefore, the main objective of this observational, retrospective single-centre study is to compare the long-term survival of octogenarians that have undergone surgical aortic valve replacement (AVR) to the survival of the general population of the same age and to establish whether any perioperative characteristics can anticipate a poor long-term result, limiting the prognostic advantage of the procedure at this age. From 2000 to 2014, 264 octogenarians underwent AVR at our institution. Perioperative data were retrieved from our institutional database and patients were followed up by telephonic interviews. The follow-up ranged between 2 months and 14.9 years (mean 4.1 +/- 3.1 years) and the completeness was 99.2 %. Logistic multivariate analysis and Cox regression were respectively applied to identify the risk factors of in-hospital mortality and follow-up survival. Our patient population ages ranged between 80 and 88 years. Isolated AVR (I-AVR) was performed in 136 patients (51.5 %) whereas combined AVR (C-AVR) in 128 patients (48.5 %). Elective procedures were 93.1 %. Logistic EuroSCORE was 15.4 +/- 10.6. In-hospital mortality was 4.5 %. Predictive factors of in-hospital mortality were the non elective priority of the procedure (OR 5.7, CI 1.28-25.7, p = 0.02), cardiopulmonary bypass time (OR 1.02, CI 1.01-1.03, p = 0.004) and age (OR 1.36, CI 1.01-1.84, p = 0.04). Follow-up survival at 1, 4, 8 and 12 years was 93.4 % +/ 1.6 %, 72.1 % +/- 3.3 %, 39.1 % +/- 4.8 % and 20.1 % +/- 5.7 %, respectively. The long-term survival of these patients was not statistically different from the survival of an age/gender-matched general population living in the same geographic region (p = 0.52). Predictive factors of poor long-term survival were diabetes mellitus (HR 1.55, CI 1.01-2.46, p = 0.05), preoperative creatinine >200 MUmol/L (HR 2.07, CI 1.21-3.53, p = 0.007) and preoperative atrial fibrillation (HR 1.79, CI 1.14-2.80, p = 0.01). In our experience, AVR can be safely performed in octogenarians. After a successful operation, the survival of these patients returns similar to the general population. Nevertheless, the preoperative presence of major comorbidities such as diabetes mellitus, renal dysfunction and atrial fibrillation significantly impact on long-term results. PMID- 26843195 TI - Cardiac fibrosis detected by magnetic resonance imaging on predicting time course diversity of left ventricular reverse remodeling in patients with idiopathic dilated cardiomyopathy. AB - This study aimed to identify the association between the time course of left ventricular reverse remodeling (LVRR) and late gadolinium enhancement in cardiac magnetic resonance imaging (LGE-cMRI) in patients with idiopathic dilated cardiomyopathy (IDCM). We identified 214 IDCM patients treated by optimal pharmacotherapies. LVRR was defined as >=10 % increment in LV ejection fraction along with >=10 % reduction in LV end-diastolic dimension. Findings of LGE-cMRI focusing on presence and extent of LGE were evaluated at baseline. Echocardiographic evaluation for detecting LVRR was performed in all patients for 3 years. The primary endpoint was defined as composite events (CEs) including readmission for heart failure, detection of major ventricular arrhythmia, and all cause mortality. LVRR was found at <1 year in 59 patients (28 %, early responder), >=1 year in 56 patients (26 %, late responder), and was absent in 99 patients (46 %, non-responder). Multivariate Cox-proportional hazards analysis revealed that both early responders (P = 0.02) and late responders (P < 0.001) had lower incidence of CEs than non-responders. Among 66 subjects (23 %) with complete cMRI evaluation, LGE was detected more often in late and non- than early responders (65, 83 vs. 23 % P < 0.001, respectively), whereas the LGE area was smaller in both early and late than non-responders (2 +/- 3, 4 +/- 3 vs. 12 +/- 10 %, P < 0.001, respectively). In conclusion, evaluating the presence and the extent of LGE is useful for predicting the clinical differences of LVRR time course and subsequent long-term outcomes. PMID- 26843196 TI - Global area strain is a sensitive marker of subendocardial damage in adults after optimal repair of aortic coarctation: three-dimensional speckle-tracking echocardiography data. AB - Aortic coarctation (CoA) in adults is associated with reduced survival. Despite successful repair, some unfavorable changes in the left ventricular (LV) myocardial function are reported. Three-dimensional speckle-tracking imaging (3D STE) is a novel method that allows to assess regional myocardial function in all directions simultaneously and to calculate global area strain which integrates longitudinal and circumferential deformation. The aim of our study was to assess whether 3-D STE provides any new characteristics of LV deformation in patients with optimal CoA repair. Adults after CoA correction underwent transthoracic echocardiographic examinations. Patients with significant concomitant lesions were ruled out. Global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS) were assessed using 3D-STE (Echopac Software, GE). The data were compared with those obtained from healthy subjects. 26 adults (9F/17M; mean age 24.4 years) with repaired CoA were studied. Despite preserved LVEFs, patients with repaired CoA had decreased GAS compared with controls (-28.8 vs. -31.7 %; p = 0.007). No differences between patients and healthy subjects in terms of GLS, GCS and GRS were observed. We found a significant correlation between mean blood pressure and GAS (R = 0.39; p < 0.05). No significant influence of age at repair, CoA correction method or LV mass on three-dimensional deformation was observed. Summarizing, global area strain derived from 3D-STE may be a sensitive indicator of subclinical LV dysfunction in patients after optimal repair of CoA. Mean blood pressure, but not age at correction seems to determine LV deformation. PMID- 26843197 TI - Social isolation, loneliness and depression in young adulthood: a behavioural genetic analysis. AB - PURPOSE: To investigate the association between social isolation and loneliness, how they relate to depression, and whether these associations are explained by genetic influences. METHODS: We used data from the age-18 wave of the Environmental Risk Longitudinal Twin Study, a birth cohort of 1116 same-sex twin pairs born in England and Wales in 1994 and 1995. Participants reported on their levels of social isolation, loneliness and depressive symptoms. We conducted regression analyses to test the differential associations of isolation and loneliness with depression. Using the twin study design, we estimated the proportion of variance in each construct and their covariance that was accounted for by genetic and environmental factors. RESULTS: Social isolation and loneliness were moderately correlated (r = 0.39), reflecting the separateness of these constructs, and both were associated with depression. When entered simultaneously in a regression analysis, loneliness was more robustly associated with depression. We observed similar degrees of genetic influence on social isolation (40 %) and loneliness (38 %), and a smaller genetic influence on depressive symptoms (29 %), with the remaining variance accounted for by the non shared environment. Genetic correlations of 0.65 between isolation and loneliness and 0.63 between loneliness and depression indicated a strong role of genetic influences in the co-occurrence of these phenotypes. CONCLUSIONS: Socially isolated young adults do not necessarily experience loneliness. However, those who are lonely are often depressed, partly because the same genes influence loneliness and depression. Interventions should not only aim at increasing social connections but also focus on subjective feelings of loneliness. PMID- 26843198 TI - Combination evidence-based therapy is effective in the oldest 'old patients' following myocardial infarction. The "Salute e Benessere nell'Anziano" (SeBA) observational study. AB - Antiplatelet drugs, statins, angiotensinogen-converting enzyme inhibitors or angiotensin-II receptor blockers, and beta-blockers improve survival following myocardial infarction (MI). However, in old age they are under-prescribed, and their effectiveness in combination regimens is unproven. The aim of the study was to evaluate prescription of recommended cardiovascular drug classes and impact of a combination regimen on long-term mortality and hospitalizations. Records of 65+ years MI survivors, discharged from hospitals in four Local Health Units in Italy, were selected from administrative databases and analyzed. All-cause mortality and cardiovascular re-hospitalization in 12 months were compared across participants prescribed 0, 1, 2, 3, or 4 recommended drug classes. Out of 2626 participants (56 % men, 25 % aged 85+ years), 42 % were prescribed all, 14 % none of the recommended drug classes. The prescription rate decreased with advancing age. At all ages, mortality decreased with increasing number of drug classes prescribed: in participants aged 85+ years, adjusted hazard ratios (95 % confidence interval) for death were 0.74 (0.47-1.17), 0.52 (0.33-0.82), 0.30 (1.19-0.48), and 0.33 (0.20-0.53) for 1, 2, 3, and 4 classes prescribed, compared with none. The risk of cardiovascular re-hospitalizations decreased with an increasing number of drug classes prescribed through the age of 84 years. After MI, a combination regimen of recommended drug classes prevents long-term mortality at any age, and cardiovascular re-hospitalizations through the age of 84. Enhancing compliance with treatment guidelines may reduce the burden of mortality and hospitalizations in older MI survivors. PMID- 26843200 TI - A promising carbon-11-labeled sphingosine-1-phosphate receptor 1-specific PET tracer for imaging vascular injury. AB - BACKGROUND: Sphingosine-1-phosphate receptor 1 (S1PR1) is highly expressed in vascular smooth muscle cells from intimal lesions. PET imaging using S1PR1 as a biomarker would increase our understanding of its role in vascular pathologies including in-stent restenosis. METHODS: The S1PR1 compound TZ3321 was synthesized for in vitro characterization and labeled with Carbon-11 for in vivo studies. The biodistribution of [11C]TZ3321 was evaluated in normal mice; microPET and immunohistochemistry (IHC) studies were performed using a murine femoral artery wire-injury model of restenosis. RESULTS: The high potency of TZ3321 for S1PR1 (IC 50 = 2.13 +/- 1.63 nM), and high selectivity (>1000 nM) for S1PR1 over S1PR2 and S1PR3 were confirmed. Biodistribution data revealed prolonged retention of [11C]TZ3321 in S1PR1-enriched tissues. MicroPET imaging of [11C]TZ3321 showed higher uptake in the wire-injured arteries of ApoE-/- mice than in injured arteries of wild-type mice (SUV 0.40 +/- 0.06 vs 0.28 +/- 0.04, n = 6, P < .001); FDG-PET showed no difference (SUV 0.98 +/- 0.04 vs 0.94 +/- 0.01, n = 6, P > .05). Post-PET autoradiography showed >4-fold higher [11C]TZ3321 retention in the injured artery of ApoE-/- mice than in wild-type mice. Subsequent IHC staining confirmed higher expression of S1PR1 in the neointima of the injured artery of ApoE-/- mice than in wild-type mice. CONCLUSIONS: This preliminary study supports the potential use of PET for quantification of the S1PR1 expression as a biomarker of neointimal hyperplasia. PMID- 26843201 TI - Recovery of left ventricular function and positive remodeling post aortic valve replacement: Evidence from radionucleotide ventriculography in a patient with severe aortic insufficiency. PMID- 26843202 TI - Left ventricular mechanical dyssynchrony in patients with coronary artery disease. PMID- 26843199 TI - In vivo assessment of myocardial viability after acute myocardial infarction: A head-to-head comparison of the perfusable tissue index by PET and delayed contrast-enhanced CMR. AB - BACKGROUND: Early recognition of viable myocardium after acute myocardial infarction (AMI) is of clinical relevance, since affected segments have the potential of functional recovery. Delayed contrast-enhanced magnetic resonance imaging (DCE-CMR) has been validated extensively for the detection of viable myocardium. An alternative parameter for detecting viability is the perfusable tissue index (PTI), derived using [15O]H2O positron emission tomography (PET), which is inversely related to the extent of myocardial scar (non-perfusable tissue). The aim of the present study was to investigate the predictive value of PTI on recovery of LV function as compared to DCE-CMR in patients with AMI, after successful percutaneous coronary intervention (PCI). METHODS: Thirty-eight patients with ST elevation myocardial infarction (STEMI) successfully treated by PCI were prospectively recruited. Subjects were examined 1 week and 3 months (mean follow-up time: 97 +/- 10 days) after AMI using [15O]H2O PET and DCE-CMR to assess PTI, regional function and scar. Viability was defined as recovery of systolic wall thickening >=3.0 mm at follow-up by use of CMR. A total of 588 segments were available for serial analysis. RESULTS: At baseline, 180 segments were dysfunctional and exhibited DCE. Seventy-three (41%) of these dysfunctional segments showed full recovery during follow-up (viable), whereas 107 (59%) segments remained dysfunctional (nonviable). Baseline PTI of viable segments was 0.94 +/- 0.09 and was significantly higher compared to nonviable segments (0.80 +/- 0.13, P < .001). The optimal cut-off value for PTI was >=0.85 with a sensitivity of 85% and specificity of 72%, and an area under the curve (AUC) of 0.82. In comparison, a cut-off value of <32% for the extent of DCE resulted in a sensitivity of 72% and a specificity of 69%, and an AUC of 0.75 (AUC PTI vs DCE P = .14). CONCLUSION: Assessment of myocardial viability shortly after reperfused AMI is feasible using PET. PET-derived PTI yields a good predictive value for the recovery of LV function in PCI-treated STEMI patients, in excellent agreement with DCE-CMR. PMID- 26843203 TI - Arrhythmias in vasodilator stress testing. PMID- 26843205 TI - Intraoperative seizure and cerebrospinal fluid leak during adult cochlear implant surgery. AB - OBJECTIVE AND IMPORTANCE: To report a rare case of cerebrospinal fluid gusher and subsequent seizure immediately after cochlear implant electrode insertion. CLINICAL PRESENTATION: After the cochlear implant electrode was inserted, brisk flow of 10 mL of cerebrospinal fluid was seen. The electrode was promptly inserted and the leak was additionally sealed with fascia. Seconds later, the patient had a tonic-clonic seizure lasting 30 seconds. Two additional episodes occurred during the case. Her postoperative course was uneventful with no subsequent seizures. The device has been successfully activated. Intervention & Technique: Postoperative imaging showed correct intracochlear placement of the electrode as well as an incidental enlarged vestibular aqueduct. Neurology consultation including electroencephalogram was unremarkable. CONCLUSION: To our knowledge, this is the first report of a seizure temporally associated with cochlear implant electrode insertion. The significance and possible casual relationship between these two events is discussed. PMID- 26843206 TI - Early and persistent high level of PS 100beta is associated with increased poor neurological outcome in patients with SAH: is there a PS 100beta threshold for SAH prognosis? AB - BACKGROUND: Protein S100beta (PS100 beta) and neuron specific enolase (NSE) have been described as biological markers of neuronal damage. The purpose of our study was to assess the prognosis thresholds of these biomarkers in subarachnoid aneurysmal hemorrhage (SAH). METHODS: Forty eight patients admitted following SAH were treated by endovascular coiling. Initial neurologic severity was assessed using the World Federation Neurologic Surgeons (WFNS), Fisher grades, initial Glasgow coma scale (GCS) and SAPS II. PS100beta and NSE plasma concentration were measured daily within the first week. The primary endpoint of the study was the 6 month Glasgow Outcome Score (GOS) dichotomized as poor (GOS 1-3) or good (GOS 4 5). RESULTS: A poor outcome at 6-months was associated with significant higher levels of S100beta value from day 1 to day 7, whereas NSE values were significantly higher from day 5 to day 7. Best threshold value, for prognosis, was obtained at day 5 for PS100beta >0.13 MUg/L (specificity 0.95 95% confidence interval (CI) 0.74-1; sensitivity 0.83 95% CI 0.65-0.93) and day 7 for NSE >14.5 MUg/L (specificity 0.90 95% CI 0.67-0.98); sensitivity (0.69 95% CI 0.51-0.83)). After multivariate logistic analysis, only PS100beta at day 5 and SAPS II enabled to predict neurological outcome at 6 months (p<0.05). CONCLUSION: PS100beta >0.13 MUg/L at day 5 is an independent predicting factor of poor neurological outcome at 6 months following SAH. This result could support the use of this biomarker at the acute phase of SAH to help physician determine the prognosis. PMID- 26843207 TI - A comparison of methods to estimate photosynthetic light absorption in leaves with contrasting morphology. AB - Accurate temporal and spatial measurements of leaf optical traits (i.e., absorption, reflectance and transmittance) are paramount to photosynthetic studies. These optical traits are also needed to couple radiative transfer and physiological models to facilitate the interpretation of optical data. However, estimating leaf optical traits in leaves with complex morphologies remains a challenge. Leaf optical traits can be measured using integrating spheres, either by placing the leaf sample in one of the measuring ports (External Method) or by placing the sample inside the sphere (Internal Method). However, in leaves with complex morphology (e.g., needles), the External Method presents limitations associated with gaps between the leaves, and the Internal Method presents uncertainties related to the estimation of total leaf area. We introduce a modified version of the Internal Method, which bypasses the effect of gaps and the need to estimate total leaf area, by painting the leaves black and measuring them before and after painting. We assess and compare the new method with the External Method using a broadleaf and two conifer species. Both methods yielded similar leaf absorption estimates for the broadleaf, but absorption estimates were higher with the External Method for the conifer species. Factors explaining the differences between methods, their trade-offs and their advantages and limitations are also discussed. We suggest that the new method can be used to estimate leaf absorption in any type of leaf independently of its morphology, and be used to study further the impact of gap fraction in the External Method. PMID- 26843208 TI - Short-time xylem relaxation results in reliable quantification of embolism in grapevine petioles and sheds new light on their hydraulic strategy. AB - In recent years, the validity of embolism quantification methods has been questioned, especially for long-vesseled plants. Some studies have suggested that cutting xylem while under tension, even under water, might generate artificial cavitation. Accordingly, a rehydration procedure prior to hydraulic measurements has been recommended to avoid this artefact. On the other hand, concerns have been raised that xylem refilling might occur when samples are rehydrated. Here, we explore the potential biases affecting embolism quantification for grapevine (Vitis vinifera L.) petioles harvested under tension or after xylem relaxation. We employ direct visualization of embolism through X-ray micro-computed tomography (microCT) to test for the occurrence of fast refilling (artifactually low per cent loss of conductivity (PLC) due to rehydration prior to sample harvest) as well as excision-induced embolism (artifactually high embolism due to air introduction during harvest). Additionally, we compared the response functions of both stomatal regulation and xylem embolism to xylem pressure (Psix). Short-time (20 min) xylem tension relaxation prior to the hydraulic measurement resulted in a lower degree of embolism than found in samples harvested under native tensions, and yielded xylem vulnerability curves similar to the ones obtained using direct microCT visualization. Much longer periods of hydration (overnight) were required before xylem refilling was observed to occur. In field-grown vines, over 85% of stomatal closure occurred at less negative Psix than that required to induce 12% PLC. Our results demonstrate that relaxation of xylem tension prior to hydraulic measurement allows for the reliable quantification of native embolism in grapevine petioles. Furthermore, we find that stomatal regulation is sufficiently conservative to avoid transpiration induced cavitation. These results suggest that grapevines have evolved a strategy of cavitation resistance, rather than one of cavitation tolerance (diurnal cycles of embolism and repair). PMID- 26843209 TI - Physiological integration of connected balsam poplar ramets. AB - Clonal integration between ramets can be an ecological advantage of clonal plant species in environments where resources are patchily distributed. We investigated physiological integration among Populus balsamifera L. ramets under drought stress in order to demonstrate water sharing between connected ramets. Pairs of connected ramets were grown in separate pots in the greenhouse where half of ramets had the parental root connection severed and half were left intact. Drought stress was applied to one ramet, and growth, specific leaf area (SLA), net photosynthesis, stomatal conductance, leaf water potential and carbon isotopic composition (delta(13)C) were measured after an 8-week growing period. Droughted ramets connected to watered ramets were able to maintain high gas exchange activity and water potential, similar to watered ramets. Leaf water potential and SLA results showed that the root connection was more beneficial for proximal compared with distal ramets. The parental root connection also allowed droughted ramets to discriminate more against (13)C compared with severed ramets. In conclusion, this study shows compelling evidence of physiological integration of connected P. balsamifera ramets through water sharing. PMID- 26843210 TI - Long-term impact of Ophiostoma novo-ulmi on leaf traits and transpiration of branches in the Dutch elm hybrid 'Dodoens'. AB - To better understand the long-term impact of Ophiostoma novo-ulmi Brasier on leaf physiology in 'Dodoens', a Dutch elm disease-tolerant hybrid, measurements of leaf area, leaf dry mass, petiole anatomy, petiole hydraulic conductivity, leaf and branch water potential, and branch sap flow were performed 3 years following an initial artificial inoculation. Although fungal hyphae were detected in fully expanded leaves, neither anatomical nor morphological traits were affected, indicating that there was no impact from the fungal hyphae on the leaves during leaf expansion. In contrast, however, infected trees showed both a lower transpiration rate of branches and a lower sap flow density. The long-term persistence of fungal hyphae inside vessels decreased the xylem hydraulic conductivity, but stomatal regulation of transpiration appeared to be unaffected as the leaf water potential in both infected and non-infected trees was similarly driven by the transpirational demands. Regardless of the fungal infection, leaves with a higher leaf mass per area ratio tended to have a higher leaf area-specific conductivity. Smaller leaves had an increased number of conduits with smaller diameters and thicker cell walls. Such a pattern could increase tolerance towards hydraulic dysfunction. Measurements of water potential and theoretical xylem conductivity revealed that petiole anatomy could predict the maximal transpiration rate. Three years following fungal inoculation, phenotypic expressions for the majority of the examined traits revealed a constitutive nature for their possible role in Dutch elm disease tolerance of 'Dodoens' trees. PMID- 26843211 TI - To What Extent is FAIMS Beneficial in the Analysis of Proteins? AB - High field asymmetric waveform ion mobility spectrometry (FAIMS), also known as differential ion mobility spectrometry, is emerging as a tool for biomolecular analysis. In this article, the benefits and limitations of FAIMS for protein analysis are discussed. The principles and mechanisms of FAIMS separation of ions are described, and the differences between FAIMS and conventional ion mobility spectrometry are detailed. Protein analysis is considered from both the top-down (intact proteins) and the bottom-up (proteolytic peptides) perspective. The roles of FAIMS in the analysis of complex mixtures of multiple intact proteins and in the analysis of multiple conformers of a single protein are assessed. Similarly, the application of FAIMS in proteomics and targeted analysis of peptides are considered. PMID- 26843212 TI - Having Older Siblings is Associated with Less Severe Social Communication Symptoms in Young Children with Autism Spectrum Disorder. AB - Among typically developing children, having sibling relationships promotes the development of social skills. This is a retrospective study of the effect of having sibling/s on the severity of the clinical presentation of autism spectrum disorder (ASD). The study included 112 children, 99 males and 15 females, mean age 29.6 +/- 9.2 months, diagnosed with ASD. The study population was composed of a group of children with ASD who had older typically developing sibling/s (n = 56) pair-matched for age and cognitive level to a group of children with ASD without sibling/s. Each participant underwent a comprehensive assessment using standardized tests. The group with older sibling/s had less severe observed social deficits (Autism Diagnostic Observation Schedule-Social Affect calibrated severity scales [ADOS-SA-CSS]) and fewer reported non-verbal communication impairments (Autism Diagnostic Interview-Revised [ADI-R]). Regression analyses revealed that, for the ADOS-SA-CSS, higher cognitive level and having older sibling/s were associated with less severe observed social affect deficits. This model explained 32.0 % of the variance. For the ADI-R communication scores, older age, higher cognitive level and having older sibling/s were associated with less severe reported non-verbal communication impairments. This model explained 33.0 % of the variance. The main finding in this study is that a familial factor, specifically having older sibling/s, was associated with better social communication abilities in children with ASD, in addition to age and cognitive ability. Having sibling/s may offer opportunities for the child with ASD to experience social interactions with children and to acquire communication skills. PMID- 26843214 TI - Inhibitors in haemophilia A: a perspective on clotting factor products as a potential contributing factor. AB - INTRODUCTION: The occurrence of a neutralizing antibody in previously untreated patients (PUPs) with haemophilia A appears to be the result of an intricate interplay of both genetic and environmental factors. Recently, the type of factor VIII (FVIII) product used in the PUPs population has been implicated as a risk factor for inhibitor development. AIM: The aim of this review was to explore in a systematic manner potential hypotheses for the product-related findings in these studies (i.e. differences in the expression system of the cell lines used to produce recombinant FVIII [rFVIII], differences in the administered antigen load or changes in clinical practice over time). RESULTS: Review of the available clinical studies illustrates the high degree of variability for the risk of inhibitor development for the same products across different studies. Differences in cell lines or antigen load were not found to provide a reasonable explanation. CONCLUSION: The possibility of changes in clinical practice over time and patient selection bias (i.e. the preferential use of one product over another in patients at higher risk for inhibitors) offers a potential explanation and should be carefully considered when evaluating the studies. PMID- 26843215 TI - A sorting-to-matching method to teach compound matching to sample. AB - Individuals with developmental disabilities may fail to attend to multiple features in compound stimuli (e.g., arrays of pictures, letters within words) with detrimental effects on learning. Participants were 5 children with autism spectrum disorder who had low to intermediate accuracy scores (35% to 84%) on a computer-presented compound matching task. Sample stimuli were pairs of icons (e.g., chair-tree), the correct comparison was identical to the sample, and each incorrect comparison had one icon in common with the sample (e.g., chair-sun, airplane-tree). A 5-step tabletop sorting-to-matching training procedure was used to teach compound matching. The first step was sorting 3 single pictures; subsequent steps gradually changed the task to compound matching. If progress stalled, tasks were modified temporarily to prompt observing behavior. After tabletop training, participants were retested on the compound matching task; accuracy improved to at least 95% for all children. This procedure illustrates one way to improve attending to multiple features of compound stimuli. PMID- 26843213 TI - Markers of increased atherosclerotic risk in patients with chronic kidney disease: a preliminary study. AB - BACKGROUND: The prevalence of chronic kidney disease is rising continuously. Cardiovascular disease is among leading causes of death and premature mortality of patients with chronic kidney disease. Even the earliest stages of chronic kidney disease are associated with higher risk of subsequent coronary heart disease. The aim of this study was to determine markers of increased risk of atherosclerosis in CKD. METHODS: The study group consisted of a total of 80 patients (20 patients with stage I/II CKD, 20 with stage III CKD, 20 stage IV CKD and 20 stage V/dialysis) and 24 healthy volunteers. Levels of proteins (osteoprotegerin, osteopontin, osteocalcin, matrix gamma-carboxyglutamic acid protein, fetuin A, MMP-2, MMP-9, TIMP-1, TIMP-2) and biochemical parameters were measured to analyse their influence on atherosclerosis risk in CKD patients. Cardiac echocardiography was performed to assess structural integrity and function, presence of left ventricular hypertrophy and systolic and diastolic function dysfunction. RESULTS: This study shows that the prevalence of ventricular hypertrophy (95.3 %) and diastolic dysfunction (93.2 %) in CKD patients is high. Also E/E' ratio was significantly higher (13.6 +/- 4.4, p = 0.001), tricuspid insufficiency (27.3 in CKD I/II vs. 71.4 in CKD V, p = 0.016), contractile dysfunction (33.3 in CKD I/II vs. 78.9 in CKD V, p = 0.040), mitral valve calcification (0 in CKD I/II vs. 28.6 in CKD V, p = 0.044) and aortic valve calcification (0 in CKD I/II vs. 61.9 in CKD V, p = 0.0008) were significantly more frequent in patients with CKD stage V/dialysis than in other groups. Only MMP-2, MMP-2/TIMP-2 ratio and TIMP-1 differed significantly between groups. CONCLUSIONS: This study shows high prevalence of ventricular hypertrophy and diastolic dysfunction in CKD patients. Contractile dysfunction, mitral and aortic valve calcification in HD patients were significantly more frequent than in patients with other CKD stages. Significantly increased levels of MMP-2, MMP 2/TIMP-2 ratio and lower TIMP-1 suggests that these factors may be involved in the pathogenesis of atherosclerosis in CKD patients. PMID- 26843216 TI - Ethnic variation in the correlation between waist to height ratio and total daily insulin requirement in children with type 1 diabetes: a cross-sectional study. AB - INTRODUCTION: Total daily insulin required to achieve glycaemic control in type 1 diabetes (T1D) depends on numerous factors. Correlation of insulin requirement to body mass index and waist circumference has been variably reported in the literature and that of waist-to-height ratio has not been studied. AIMS: To study the correlation between daily insulin requirement [total daily dose (TDD)] and waist-to-height ratio (WHtR) in a multiethnic population. METHODS: A cross sectional study of children (5-18 years) with T1D attending a diabetes clinic in a multiethnic population in Bradford, UK was conducted. Physical measurements were undertaken in the clinic setting and data collected from case notes and patients/carers. RESULTS: Sixty nine patients with mean age 12.7(+/-3.1) yr, duration of diabetes 5.4(+/-3.5) yr and hemoglobin A1c (HbA1c) 80(+/ 18)mmol/mol(9.5 +/- 1.6%) were recruited. Nearly 54% (n = 37) were white and 46% were non-white (29 Asian Pakistani; 1 Indian; 2 mixed White Afro-Caribbean). The two groups had similar demographics and disease profiles. Non-whites compared with whites had a higher prevalence of obesity (15 vs 5%, p < 0.01), family history of type 2 diabetes (T2D) (49% vs. 33%), microalbuminuria (22% vs. 11%, p < 0.05) and deprivation (mean index of multiple deprivation score 42 vs. 30, p < 0.001). WHtR and TDD were poorly correlated in the whole group. There was however a significant positive correlation in Caucasians (r = 0.583, N = 37, p < 0.01) and a negative correlation in Asian Pakistanis (r = -0.472, N = 32, p < 0.01); with a significant negative correlation seen in subjects with relatives with T2D (r = -0.86, N = 6, p = 0.02). CONCLUSIONS: The variation in correlations highlights that the two ethnic groups behave differently and should therefore be studied separately with regards to factors influencing insulin requirements with careful consideration to the presence of parental IR. Further prospective studies are required to explore the reasons for these differences. PMID- 26843218 TI - Health benefits and costs of filtration interventions that reduce indoor exposure to PM2.5 during wildfires. AB - Increases in hospital admissions and deaths are associated with increases in outdoor air particles during wildfires. This analysis estimates the health benefits expected if interventions had improved particle filtration in homes in Southern California during a 10-day period of wildfire smoke exposure. Economic benefits and intervention costs are also estimated. The six interventions implemented in all affected houses are projected to prevent 11% to 63% of the hospital admissions and 7% to 39% of the deaths attributable to wildfire particles. The fraction of the population with an admission attributable to wildfire smoke is small, thus, the costs of interventions in all homes far exceeds the economic benefits of reduced hospital admissions. However, the estimated economic value of the prevented deaths exceed or far exceed intervention costs for interventions that do not use portable air cleaners. For the interventions with portable air cleaner use, mortality-related economic benefits exceed intervention costs as long as the cost of the air cleaners, which have a multi-year life, are not attributed to the short wildfire period. Cost effectiveness is improved by intervening only in the homes of the elderly who experience most of the health effects of particles from wildfires. PMID- 26843219 TI - Extensive pneumocephalus subsequent to an open skull fracture. PMID- 26843217 TI - Comparative anatomical distribution of neuronal calcium-binding protein (NECAB) 1 and -2 in rodent and human spinal cord. AB - Neuronal calcium-binding protein 1 and -2 (NECAB1/2) localize to multiple excitatory neuron populations in the mouse spinal cord. Here, we analyzed rat and human spinal cord, combining in situ hybridization and immunohistochemistry, complementing newly collated data on mouse spinal cord for direct comparisons. Necab1/2 mRNA transcripts showed complementary distribution in rodent's spinal cord. Multiple-labeling fluorescence histochemistry with neuronal phenotypic markers localized NECAB1 to a dense fiber plexus in the dorsal horn, to neurons mainly in superficial layers and to commissural interneurons in both rodent species. NECAB1-positive (+) motor neurons were only found in mice. NECAB1 distribution in the human spinal cord was similar with the addition of NECAB1 like immunoreactivity surrounding myelinated axons. NECAB2 was mainly present in excitatory synaptic boutons in the dorsal horn of all three species, and often in calbindin-D28k(+) neuronal somata. Rodent ependymal cells expressed calbindin D28k. In humans, they instead were NECAB2(+) and/or calretinin(+). Our results reveal that the association of NECAB2 to excitatory neuronal circuits in the spinal cord is evolutionarily conserved across the mammalian species investigated so far. In contrast, NECAB1 expression is more heterogeneous. Thus, our study suggests that the phenotypic segregation of NECAB1 and -2 to respective excitatory and inhibitory spinal systems can underpin functional modalities in determining the fidelity of synaptic neurotransmission and neuronal responsiveness, and might bear translational relevance to humans. PMID- 26843220 TI - Metastatic small bowel neuroendocrine tumour with bilateral carcinoid heart disease. AB - A 63-year-old woman was admitted with a year's history of exertional breathlessness, anxiety attacks, syncopal episodes, diarrhoea, fatigue, reduced appetite, 2 stones weight loss, and flushing affecting her face and trunk. Investigations revealed raised urine 5-hydroxy indole acetic acid (5-HIAA) and chromogranin A. CT scan demonstrated extensive soft tissue encasing the major vessels intra-abdominally, and a retroperitoneal mass. (111)In-octreotide single photon emission CT (SPECT CT) showed increased focal activity in the mediastinum, retroperitoneum and mesenteric lymph nodes. Para aortic lymph node biopsy confirmed the diagnosis of metastatic well-differentiated grade 1 gastrointestinal neuroendocrine tumour (NET). Extensive cardiac investigations confirmed severe mitral regurgitation, moderate aortic and tricuspid regurgitation, and mild pulmonary regurgitation. The patient's symptoms of flushing and diarrhoea were controlled with octreotide LAR, and she underwent mechanical aortic and mitral valve replacement. Following discharge from surgery, she went on to develop hydronephrosis and urosepsis, followed by infective endocarditis, resulting in recurrent admissions, and eventually passed away in her sleep nearly 14 months after her initial diagnosis. PMID- 26843221 TI - Adenoid cystic carcinoma: triple negative breast cancer with good prognosis. AB - Adenoid cystic carcinoma of the breast (ACCb) is a rare type of breast cancer. The treatment is not consensual. The authors report two cases of ACCb. Case 1: A 59-year-old woman with T1bN0M0, who went for lumpectomy and adjuvant radiation therapy (RT) (60 Gy in 30 fractions); Case 2: A 43-year-old woman, who went for modified radical mastectomy with T3N1M0, and underwent adjuvant chemotherapy, and a sequential regimen with antracyclin and taxane, prior to adjuvant RT (50 Gy/25 fractions). PMID- 26843223 TI - Muscular tendinous junction rupture of the posterior tibial tendon after closed bimalleolar ankle fracture. AB - In this case report, we present an acute rupture in the muscular tendinous junction of a posterior tibialis muscle in a bimalleolar closed ankle fracture after a high-energy trauma in a 30-year-old patient with no significant medical history. Fracture was confirmed by simple X-rays, and was treated with an open reduction in which both of the fractures were treated with osteosynthesis material and reparation of the syndesmosis. If left untreated, this uncommon finding can result in a bad postsurgical outcome; we believe this injury is more common but under-reported in the literature. The surgeon should be aware and look specifically for this type of lesion during the procedure. Finding and treating this injury requires special postoperative care, non-weight-bearing instructions and balanced physiotherapy. PMID- 26843222 TI - Spontaneously recovered severe thrombocytopaenia following zoledronic acid infusion for osteoporosis. AB - Zoledronic acid is widely used for the treatment of various skeletal disorders. While acute phase reactions are commonly seen, hypocalcaemia, femoral shaft fractures, osteonecrosis of the jaw and renal failure are rare. Two cases of fatal thrombocytopaenic purpura have been reported following zoledronic acid infusion. We report a case of non-fatal thrombocytopaenia with spontaneous recovery. A 70-year woman with osteoporosis participated in a research study. Complete blood and platelet counts prior to zoledronic acid infusion were normal (138,000/uL), but had declined slightly from 185,000/uL 2 years ago. One year after the first zoledronic acid infusion, her platelet count declined to 50,000/uL without any clinical manifestations, and rose slowly returning to normal (156,000/uL) over the next 1 year. Extensive evaluation did not reveal any specific abnormalities, and the pathogenesis of her transient severe thrombocytopaenia after two infusions of zoledronic acid remains unclear. PMID- 26843224 TI - Umbilical cord haematoma and adrenal haemorrhage in a macrosomic neonate with anaemia. PMID- 26843225 TI - Making a dent with corticosteroid injections for de Quervain's tenosynovitis. PMID- 26843226 TI - Point/Counterpoint. Particle therapy is ideal for the treatment of ocular melanomas. PMID- 26843227 TI - Experimental verification of gain drop due to general ion recombination for a carbon-ion pencil beam. AB - PURPOSE: Accurate dose measurement in radiotherapy is critically dependent on correction for gain drop, which is the difference of the measured current from the ideal saturation current due to general ion recombination. Although a correction method based on the Boag theory has been employed, the theory assumes that ionized charge density in an ionization chamber (IC) is spatially uniform throughout the irradiation volume. For particle pencil beam scanning, however, the charge density is not uniform, because the fluence distribution of a pencil beam is not uniform. The aim of this study was to verify the effect of the nonuniformity of ionized charge density on the gain drop due to general ion recombination. METHODS: The authors measured the saturation curve, namely, the applied voltage versus measured current, using a large plane-parallel IC and 24 channel parallel-plate IC with concentric electrodes. To verify the effect of the nonuniform ionized charge density on the measured saturation curve, the authors calculated the saturation curve using a method which takes into account the nonuniform ionized charge density and compared it with the measured saturation curves. RESULTS: Measurement values of the different saturation curves in the different channels of the concentric electrodes differed and were consistent with the calculated values. The saturation curves measured by the large plane-parallel IC were also consistent with the calculation results, including the estimation error of beam size and of setup misalignment. Although the impact of the nonuniform ionized charge density on the gain drop was clinically negligible with the conventional beam intensity, it was expected that the impact would increase with higher ionized charge density. CONCLUSIONS: For pencil beam scanning, the assumption of the conventional Boag theory is not valid. Furthermore, the nonuniform ionized charge density affects the prediction accuracy of gain drop when the ionized charge density is increased by a higher dose rate and/or lower beam size. PMID- 26843229 TI - Accurate modeling and positioning of a magnetically controlled catheter tip. AB - PURPOSE: This paper represents the initial phase of a proposed operator-friendly semiautomatic method for positioning and directing an intravascular three-magnet tip catheter in the human heart using an electromagnetic system. METHODS: A predictive computer algorithm based on a comprehensive mathematical model is developed, which accurately calculates the magnetic field generated by the electromagnet system as well as the magnetic torques and forces exerted on a three-magnet tip catheter, and generates the necessary electromagnet currents for arbitrary displacement and deflection of the catheter tip within a workspace of 128 * 128 * 128 mm. RESULTS: We demonstrate the ability of the developed mathematical model to accurately position a three-magnet tip catheter within the 128 * 128 * 128 mm workspace of a 3D eight-electromagnet system. CONCLUSIONS: The ability of the developed mathematical model in predicting the displacement, direction, and deflection of the catheter tip as a function of the electromagnet current values has been verified through experimental results. PMID- 26843228 TI - Technical Note: On GAFChromic EBT-XD film and the lateral response artifact. AB - PURPOSE: The new radiochromic film, GAFChromic EBT-XD, contains the same active material, lithium-10,12-pentacosadiynoate, as GAFChromic EBT3, but the crystalline form is different. This work investigates the effect of this change on the well-known lateral response artifact when EBT-XD film is digitized on a flatbed scanner. METHODS: The dose response of a single production lot of EBT-XD was characterized by scanning an unexposed film plus a set of films exposed to doses between 2.5 and 50 Gy using 6 MV photons. To characterize the lateral response artifact, the authors used the unexposed film plus a subset of samples exposed to doses between 20 and 50 Gy. Digital images of these films were acquired at seven discrete lateral locations perpendicular to the scan direction on three Epson 10000XL scanners. Using measurements at the discrete lateral positions, the scanner responses were determined as a function of the lateral position of the film. From the data for each scanner, a set of coefficients were derived whereby measured response values could be corrected to remove the effects of the lateral response artifact. The EBT-XD data were analyzed as in their previous work and compared to results reported for EBT3 in that paper. RESULTS: For films scanned in the same orientation and having equal responses, the authors found that the lateral response artifact for EBT-XD and EBT3 films was remarkably similar. For both films, the artifact increases with increased net response. However, as EBT-XD is less sensitive than EBT3, a greater exposure dose is required to reach the same net response. On this basis, the lower sensitivity of EBT-XD relative to EBT3 results in less net response change for equal exposure and a reduction in the impact of the lateral response artifact. CONCLUSIONS: The shape of the crystalline active component in EBT-XD and EBT3 does not affect the fundamental existence of the lateral response artifact when the films are digitized on flatbed scanners. Owing its lower sensitivity, EBT-XD film requires higher dose to reach the same response as EBT3, resulting in lesser impact of the lateral response artifact. For doses >10 Gy, the slopes of the EBT-XD red and green channel dose response curves are greater than the corresponding ones for EBT3. For these two reasons, the authors prefer EBT-XD for doses exceeding about 10 Gy. PMID- 26843230 TI - Novel scintillation detector design and performance for proton radiography and computed tomography. AB - PURPOSE: Proton computed tomography (pCT) will enable accurate prediction of proton and ion range in a patient while providing the benefit of lower radiation exposure than in x-ray CT. The accuracy of the range prediction is essential for treatment planning in proton or ion therapy and depends upon the detector used to evaluate the water-equivalent path length (WEPL) of a proton passing through the object. A novel approach is presented for an inexpensive WEPL detector for pCT and proton radiography. METHODS: A novel multistage detector with an aperture of 10 * 37.5 cm was designed to optimize the accuracy of the WEPL measurements while simplifying detector construction and the performance requirements of its components. The design of the five-stage detector was optimized through simulations based on the geant4 detector simulation toolkit, and the fabricated prototype was calibrated in water-equivalent millimeters with 200 MeV protons in the research beam line of the clinical proton synchrotron at Loma Linda University Medical Center. A special polystyrene step phantom was designed and built to speed up and simplify the calibration procedure. The calibrated five stage detector was tested in the 200 MeV proton beam as part of the pCT head scanner, using a water phantom and polystyrene slabs to verify the WEPL reconstruction accuracy. RESULTS: The beam-test results demonstrated excellent performance of the new detector, in good agreement with the simulation results. The WEPL measurement accuracy is about 3.0 mm per proton in the 0-260 mm WEPL range required for a pCT head scan with a 200 MeV proton beam. CONCLUSIONS: The new multistage design approach to WEPL measurements for proton CT and radiography has been prototyped and tested. The test results show that the design is competitive with much more expensive calorimeter and range-counter designs. PMID- 26843231 TI - Intracranial hemorrhage alters scalp potential distribution in bioimpedance cerebral monitoring: Preliminary results from FEM simulation on a realistic head model and human subjects. AB - PURPOSE: Current diagnostic neuroimaging for detection of intracranial hemorrhage (ICH) is limited to fixed scanners requiring patient transport and extensive infrastructure support. ICH diagnosis would therefore benefit from a portable diagnostic technology, such as electrical bioimpedance (EBI). Through simulations and patient observation, the authors assessed the influence of unilateral ICH hematomas on quasisymmetric scalp potential distributions in order to establish the feasibility of EBI technology as a potential tool for early diagnosis. METHODS: Finite element method (FEM) simulations and experimental left-right hemispheric scalp potential differences of healthy and damaged brains were compared with respect to the asymmetry caused by ICH lesions on quasisymmetric scalp potential distributions. In numerical simulations, this asymmetry was measured at 25 kHz and visualized on the scalp as the normalized potential difference between the healthy and ICH damaged models. Proof-of-concept simulations were extended in a pilot study of experimental scalp potential measurements recorded between 0 and 50 kHz with the authors' custom-made bioimpedance spectrometer. Mean left-right scalp potential differences recorded from the frontal, central, and parietal brain regions of ten healthy control and six patients suffering from acute/subacute ICH were compared. The observed differences were measured at the 5% level of significance using the two-sample Welch t-test. RESULTS: The 3D-anatomically accurate FEM simulations showed that the normalized scalp potential difference between the damaged and healthy brain models is zero everywhere on the head surface, except in the vicinity of the lesion, where it can vary up to 5%. The authors' preliminary experimental results also confirmed that the left-right scalp potential difference in patients with ICH (e.g., 64 mV) is significantly larger than in healthy subjects (e.g., 20.8 mV; P < 0.05). CONCLUSIONS: Realistic, proof-of-concept simulations confirmed that ICH affects quasisymmetric scalp potential distributions. Pilot clinical observations with the authors' custom-made bioimpedance spectrometer also showed higher left-right potential differences in the presence of ICH, similar to those of their simulations, that may help to distinguish healthy subjects from ICH patients. Although these pilot clinical observations are in agreement with the computer simulations, the small sample size of this study lacks statistical power to exclude the influence of other possible confounders such as age, sex, and electrode positioning. The agreement with previously published simulation-based and clinical results, however, suggests that EBI technology may be potentially useful for ICH detection. PMID- 26843233 TI - High-resolution x-ray imaging using a structured scintillator. AB - PURPOSE: In this study, the authors introduce a new generation of finely structured scintillators with a very high spatial resolution (a few micrometers) compared to conventional scintillators, yet maintaining a thick absorbing layer for improved detectivity. METHODS: Their concept is based on a 2D array of high aspect ratio pores which are fabricated by ICP etching, with spacings (pitches) of a few micrometers, on silicon and oxidation of the pore walls. The pores were subsequently filled by melting of powdered CsI(Tl), as the scintillating agent. In order to couple the secondary emitted photons of the back of the scintillator array to a CCD device, having a larger pixel size than the pore pitch, an open optical microscope with adjustable magnification was designed and implemented. By imaging a sharp edge, the authors were able to calculate the modulation transfer function (MTF) of this finely structured scintillator. RESULTS: The x-ray images of individually resolved pores suggest that they have been almost uniformly filled, and the MTF measurements show the feasibility of a few microns spatial resolution imaging, as set by the scintillator pore size. Compared to existing techniques utilizing CsI needles as a structured scintillator, their results imply an almost sevenfold improvement in resolution. Finally, high resolution images, taken by their detector, are presented. CONCLUSIONS: The presented work successfully shows the functionality of their detector concept for high resolution imaging and further fabrication developments are most likely to result in higher quantum efficiencies. PMID- 26843232 TI - Can conclusions drawn from phantom-based image noise assessments be generalized to in vivo studies for the nonlinear model-based iterative reconstruction method? AB - PURPOSE: Phantom-based objective image quality assessment methods are widely used in the medical physics community. For a filtered backprojection (FBP) reconstruction-based linear or quasilinear imaging system, the use of this methodology is well justified. Many key image quality metrics acquired with phantom studies can be directly applied to in vivo human subject studies. Recently, a variety of image quality metrics have been investigated for model based iterative image reconstruction (MBIR) methods and several novel characteristics have been discovered in phantom studies. However, the following question remains unanswered: can certain results obtained from phantom studies be generalized to in vivo animal studies and human subject studies? The purpose of this paper is to address this question. METHODS: One of the most striking results obtained from phantom studies is a novel power-law relationship between noise variance of MBIR (sigma(2)) and tube current-rotation time product (mAs): sigma(2) ? (mAs)(-0.4) [K. Li et al., "Statistical model based iterative reconstruction (MBIR) in clinical CT systems: Experimental assessment of noise performance," Med. Phys. 41, 041906 (15pp.) (2014)]. To examine whether the same power-law works for in vivo cases, experimental data from two types of in vivo studies were analyzed in this paper. All scans were performed with a 64-slice diagnostic CT scanner (Discovery CT750 HD, GE Healthcare) and reconstructed with both FBP and a MBIR method (Veo, GE Healthcare). An Institutional Animal Care and Use Committee-approved in vivo animal study was performed with an adult swine at six mAs levels (10-290). Additionally, human subject data (a total of 110 subjects) acquired from an IRB-approved clinical trial were analyzed. In this clinical trial, a reduced-mAs scan was performed immediately following the standard mAs scan; the specific mAs used for the two scans varied across human subjects and were determined based on patient size and clinical indications. The measurements of sigma(2) were performed at different mAs by drawing regions-of interest (ROIs) in the liver and the subcutaneous fat. By applying a linear least squares regression, the beta values in the power-law relationship sigma(2) ? (mAs)(-beta) were measured for the in vivo data and compared with the value found in phantom experiments. RESULTS: For the in vivo swine study, an exponent of beta = 0.43 was found for MBIR, and the coefficient of determination (R(2)) for the corresponding least-squares power-law regression was 0.971. As a reference, the beta and R(2) values for FBP were found to be 0.98 and 0.997, respectively, from the same study, which are consistent with the well-known sigma(2) ? (mAs)(-1.0) relationship for linear CT systems. For the human subject study, the measured beta values for the MBIR images were 0.41 +/- 0.12 in the liver and 0.37 +/- 0.12 in subcutaneous fat. In comparison, the beta values for the FBP images were 1.04 +/- 0.10 in the liver and 0.97 +/- 0.12 in subcutaneous fat. The beta values of MBIR and FBP obtained from the in vivo studies were found to be statistically equivalent to the corresponding beta values from the phantom study within an equivalency interval of [ - 0.1, 0.1] (p < 0.05); across MBIR and FBP, the difference in beta was statistically significant (p < 0.05). CONCLUSIONS: Despite the nonlinear nature of the MBIR method, the power-law relationship, sigma(2) ? (mAs)(-0.4), found from phantom studies can be applied to in vivo animal and human subject studies. PMID- 26843234 TI - Classification of arterial and venous cerebral vasculature based on wavelet postprocessing of CT perfusion data. AB - PURPOSE: The purpose of this study was to propose and evaluate a new wavelet based technique for classification of arterial and venous vessels using time resolved cerebral CT perfusion data sets. METHODS: Fourteen consecutive patients (mean age 73 yr, range 17-97) with suspected stroke but no pathology in follow-up MRI were included. A CT perfusion scan with 32 dynamic phases was performed during intravenous bolus contrast-agent application. After rigid-body motion correction, a Paul wavelet (order 1) was used to calculate voxelwise the wavelet power spectrum (WPS) of each attenuation-time course. The angiographic intensity A was defined as the maximum of the WPS, located at the coordinates T (time axis) and W (scale/width axis) within the WPS. Using these three parameters (A, T, W) separately as well as combined by (1) Fisher's linear discriminant analysis (FLDA), (2) logistic regression (LogR) analysis, or (3) support vector machine (SVM) analysis, their potential to classify 18 different arterial and venous vessel segments per subject was evaluated. RESULTS: The best vessel classification was obtained using all three parameters A and T and W [area under the curve (AUC): 0.953 with FLDA and 0.957 with LogR or SVM]. In direct comparison, the wavelet-derived parameters provided performance at least equal to conventional attenuation-time-course parameters. The maximum AUC obtained from the proposed wavelet parameters was slightly (although not statistically significantly) higher than the maximum AUC (0.945) obtained from the conventional parameters. CONCLUSIONS: A new method to classify arterial and venous cerebral vessels with high statistical accuracy was introduced based on the time-domain wavelet transform of dynamic CT perfusion data in combination with linear or nonlinear multidimensional classification techniques. PMID- 26843235 TI - 4D ML reconstruction as a tool for volumetric PET-based treatment verification in ion beam radiotherapy. AB - PURPOSE: An innovative strategy to improve the sensitivity of positron emission tomography (PET)-based treatment verification in ion beam radiotherapy is proposed. METHODS: Low counting statistics PET images acquired during or shortly after the treatment (Measured PET) and a Monte Carlo estimate of the same PET images derived from the treatment plan (Expected PET) are considered as two frames of a 4D dataset. A 4D maximum likelihood reconstruction strategy was adapted to iteratively estimate the annihilation events distribution in a reference frame and the deformation motion fields that map it in the Expected PET and Measured PET frames. The outputs generated by the proposed strategy are as follows: (1) an estimate of the Measured PET with an image quality comparable to the Expected PET and (2) an estimate of the motion field mapping Expected PET to Measured PET. The details of the algorithm are presented and the strategy is preliminarily tested on analytically simulated datasets. RESULTS: The algorithm demonstrates (1) robustness against noise, even in the worst conditions where 1.5 * 10(4) true coincidences and a random fraction of 73% are simulated; (2) a proper sensitivity to different kind and grade of mismatches ranging between 1 and 10 mm; (3) robustness against bias due to incorrect washout modeling in the Monte Carlo simulation up to 1/3 of the original signal amplitude; and (4) an ability to describe the mismatch even in presence of complex annihilation distributions such as those induced by two perpendicular superimposed ion fields. CONCLUSIONS: The promising results obtained in this work suggest the applicability of the method as a quantification tool for PET-based treatment verification in ion beam radiotherapy. An extensive assessment of the proposed strategy on real treatment verification data is planned. PMID- 26843236 TI - Dosimetric and delivery efficiency investigation for treating hepatic lesions with a MLC-equipped robotic radiosurgery-radiotherapy combined system. AB - PURPOSE: The CyberKnife M6 (CK-M6) Series introduced a multileaf collimator (MLC) for extending its capability from stereotactic radiosurgery/stereotactic radiotherapy (SBRT) to conventionally fractionated radiotherapy. This work is to investigate the dosimetric quality of plans that are generated using MLC-shaped beams on the CK-M6, as well as their delivery time, via comparisons with the intensity modulated radiotherapy plans that were clinically used on a Varian Linac for treating hepatic lesions. METHODS: Nine patient cases were selected and divided into three groups with three patients in each group: (1) the group-one patients were treated conventionally (25 fractions); (2) the group-two patients were treated with SBRT-like hypofractionation (5 fractions); and (3) the group three patients were treated similar to group-one patients, but with two planning target volumes (PTVs) and two different prescription dose levels correspondingly. The clinically used plans were generated on the eclipse treatment planning system (TPS) and delivered on a Varian Linac (E-V plans). The multiplan (MP) TPS was used to replan these clinical cases with the MLC as the beam device for the CK-M6 (C-M plans). After plans were normalized to the same PTV dose coverage, comparisons between the C-M and E-V plans were performed based on D(99%) (percentage of prescription dose received by 99% of the PTV), D(0.1cm(3)) (the percentage of prescription dose to 0.1 cm(3) of the PTV), and doses received by critical structures. Then, the delivery times for the C-M plans will be obtained, which are the MP TPS generated estimations assuming having an imaging interval of 60 s. RESULTS: The difference in D(99%) between C-M and E-V plans is +0.6% on average (+ or - indicating a higher or lower dose from C-M plans than from E-V plans) with a range from -4.1% to +3.8%, and the difference in D(0.1cm(3)) was 1.0% on average with a range from -5.1% to +2.9%. The PTV conformity index (CI) for the C-M plans ranges from 1.07 to 1.29 with a mean of 1.19, slightly inferior to the E-V plans, in which the CI ranges from 1.00 to 1.15 with a mean of 1.07. Accounting for all nine patients in three groups, 45% of the critical structures received a lower mean dose for the C-M plans as compared with the E-V plans, and similarly, 48% received a lower maximum dose. Furthermore, the average difference of the mean critical structure dose between the C-M and E-V plans over all critical structures for all patients showed only +2.10% relative to the prescription dose and the similar comparison finds the average difference of the maximum critical structure dose of only +1.24%. The estimated delivery times for the C-M plans on the CK-M6 range from 18 to 24 minutes while they are from 7 to 13.7 min for the E-V plans on the Varian Linac. CONCLUSIONS: For treating hepatic lesions, for the C-M plans that are comparable to E-V plans in quality, the times needed to deliver these C-M plans on the CK-M6 are longer than the delivery time for the E-V plans on the Varian Linac, but may be clinically acceptable. PMID- 26843237 TI - A validated tumor control probability model based on a meta-analysis of low, intermediate, and high-risk prostate cancer patients treated by photon, proton, or carbon-ion radiotherapy. AB - PURPOSE: A fully heterogeneous population averaged mechanistic tumor control probability (TCP) model is appropriate for the analysis of external beam radiotherapy (EBRT). This has been accomplished for EBRT photon treatment of intermediate-risk prostate cancer. Extending the TCP model for low and high-risk patients would be beneficial in terms of overall decision making. Furthermore, different radiation treatment modalities such as protons and carbon-ions are becoming increasingly available. Consequently, there is a need for a complete TCP model. METHODS: A TCP model was fitted and validated to a primary endpoint of 5 year biological no evidence of disease clinical outcome data obtained from a review of the literature for low, intermediate, and high-risk prostate cancer patients (5218 patients fitted, 1088 patients validated), treated by photons, protons, or carbon-ions. The review followed the preferred reporting item for systematic reviews and meta-analyses statement. Treatment regimens include standard fractionation and hypofractionation treatments. Residual analysis and goodness of fit statistics were applied. RESULTS: The TCP model achieves a good level of fit overall, linear regression results in a p-value of <0.000 01 with an adjusted-weighted-R(2) value of 0.77 and a weighted root mean squared error (wRMSE) of 1.2%, to the fitted clinical outcome data. Validation of the model utilizing three independent datasets obtained from the literature resulted in an adjusted-weighted-R(2) value of 0.78 and a wRMSE of less than 1.8%, to the validation clinical outcome data. The weighted mean absolute residual across the entire dataset is found to be 5.4%. CONCLUSIONS: This TCP model fitted and validated to clinical outcome data, appears to be an appropriate model for the inclusion of all clinical prostate cancer risk categories, and allows evaluation of current EBRT modalities with regard to tumor control prediction. PMID- 26843238 TI - Parameterization of photon beam dosimetry for a linear accelerator. AB - PURPOSE: In radiation therapy, accurate data acquisition of photon beam dosimetric quantities is important for (1) beam modeling data input into a treatment planning system (TPS), (2) comparing measured and TPS modeled data, (3) the quality assurance process of a linear accelerator's (Linac) beam characteristics, (4) the establishment of a standard data set for comparison with other data, etcetera. Parameterization of the photon beam dosimetry creates a data set that is portable and easy to implement for different applications such as those previously mentioned. The aim of this study is to develop methods to parameterize photon beam dosimetric quantities, including percentage depth doses (PDDs), profiles, and total scatter output factors (S(cp)). METHODS: S(cp), PDDs, and profiles for different field sizes, depths, and energies were measured for a Linac using a cylindrical 3D water scanning system. All data were smoothed for the analysis and profile data were also centered, symmetrized, and geometrically scaled. The S(cp) data were analyzed using an exponential function. The inverse square factor was removed from the PDD data before modeling and the data were subsequently analyzed using exponential functions. For profile modeling, one halfside of the profile was divided into three regions described by exponential, sigmoid, and Gaussian equations. All of the analytical functions are field size, energy, depth, and, in the case of profiles, scan direction specific. The model's parameters were determined using the minimal amount of measured data necessary. The model's accuracy was evaluated via the calculation of absolute differences between the measured (processed) and calculated data in low gradient regions and distance-to-agreement analysis in high gradient regions. Finally, the results of dosimetric quantities obtained by the fitted models for a different machine were also assessed. RESULTS: All of the differences in the PDDs' buildup and the profiles' penumbra regions were less than 2 and 0.5 mm, respectively. The differences in the low gradient regions were 0.20% +/- 0.20% (<1% for all) and 0.50% +/- 0.35% (<1% for all) for PDDs and profiles, respectively. For S(cp) data, all of the absolute differences were less than 0.5%. CONCLUSIONS: This novel analytical model with minimum measurement requirements was proved to accurately calculate PDDs, profiles, and S(cp) for different field sizes, depths, and energies. PMID- 26843239 TI - Monte Carlo simulations of 3He ion physical characteristics in a water phantom and evaluation of radiobiological effectiveness. AB - PURPOSE: (3)He ions may hold great potential for clinical therapy because of both their physical and biological properties. In this study, the authors investigated the physical properties, i.e., the depth-dose curves from primary and secondary particles, and the energy distributions of helium ((3)He) ions. A relative biological effectiveness (RBE) model was applied to assess the biological effectiveness on survival of multiple cell lines. METHODS: In light of the lack of experimental measurements and cross sections, the authors used Monte Carlo methods to study the energy deposition of (3)He ions. The transport of (3)He ions in water was simulated by using three Monte Carlo codes-FLUKA, GEANT4, and MCNPX for incident beams with Gaussian energy distributions with average energies of 527 and 699 MeV and a full width at half maximum of 3.3 MeV in both cases. The RBE of each was evaluated by using the repair-misrepair-fixation model. In all of the simulations with each of the three Monte Carlo codes, the same geometry and primary beam parameters were used. RESULTS: Energy deposition as a function of depth and energy spectra with high resolution was calculated on the central axis of the beam. Secondary proton dose from the primary (3)He beams was predicted quite differently by the three Monte Carlo systems. The predictions differed by as much as a factor of 2. Microdosimetric parameters such as dose mean lineal energy (y(D)), frequency mean lineal energy (y(F)), and frequency mean specific energy (z(F)) were used to characterize the radiation beam quality at four depths of the Bragg curve. Calculated RBE values were close to 1 at the entrance, reached on average 1.8 and 1.6 for prostate and head and neck cancer cell lines at the Bragg peak for both energies, but showed some variations between the different Monte Carlo codes. CONCLUSIONS: Although the Monte Carlo codes provided different results in energy deposition and especially in secondary particle production (most of the differences between the three codes were observed close to the Bragg peak, where the energy spectrum broadens), the results in terms of RBE were generally similar. PMID- 26843240 TI - Technical Note: Spot characteristic stability for proton pencil beam scanning. AB - PURPOSE: The spot characteristics for proton pencil beam scanning (PBS) were measured and analyzed over a 16 month period, which included one major site configuration update and six cyclotron interventions. The results provide a reference to establish the quality assurance (QA) frequency and tolerance for proton pencil beam scanning. METHODS: A simple treatment plan was generated to produce an asymmetric 9-spot pattern distributed throughout a field of 16 * 18 cm for each of 18 proton energies (100.0-226.0 MeV). The delivered fluence distribution in air was measured using a phosphor screen based CCD camera at three planes perpendicular to the beam line axis (x-ray imaging isocenter and up/down stream 15.0 cm). The measured fluence distributions for each energy were analyzed using in-house programs which calculated the spot sizes and positional deviations of the Gaussian shaped spots. RESULTS: Compared to the spot characteristic data installed into the treatment planning system, the 16-month averaged deviations of the measured spot sizes at the isocenter plane were 2.30% and 1.38% in the IEC gantry x and y directions, respectively. The maximum deviation was 12.87% while the minimum deviation was 0.003%, both at the upstream plane. After the collinearity of the proton and x-ray imaging system isocenters was optimized, the positional deviations of the spots were all within 1.5 mm for all three planes. During the site configuration update, spot positions were found to deviate by 6 mm until the tuning parameters file was properly restored. CONCLUSIONS: For this beam delivery system, it is recommended to perform a spot size and position check at least monthly and any time after a database update or cyclotron intervention occurs. A spot size deviation tolerance of <15% can be easily met with this delivery system. Deviations of spot positions were <2 mm at any plane up/down stream 15 cm from the isocenter. PMID- 26843241 TI - Technical aspects of real time positron emission tracking for gated radiotherapy. AB - PURPOSE: Respiratory motion can lead to treatment errors in the delivery of radiotherapy treatments. Respiratory gating can assist in better conforming the beam delivery to the target volume. We present a study of the technical aspects of a real time positron emission tracking system for potential use in gated radiotherapy. METHODS: The tracking system, called PeTrack, uses implanted positron emission markers and position sensitive gamma ray detectors to track breathing motion in real time. PeTrack uses an expectation-maximization algorithm to track the motion of fiducial markers. A normalized least mean squares adaptive filter predicts the location of the markers a short time ahead to account for system response latency. The precision and data collection efficiency of a prototype PeTrack system were measured under conditions simulating gated radiotherapy. The lung insert of a thorax phantom was translated in the inferior superior direction with regular sinusoidal motion and simulated patient breathing motion (maximum amplitude of motion +/-10 mm, period 4 s). The system tracked the motion of a (22)Na fiducial marker (0.34 MBq) embedded in the lung insert every 0.2 s. The position of the was marker was predicted 0.2 s ahead. For sinusoidal motion, the equation used to model the motion was fitted to the data. The precision of the tracking was estimated as the standard deviation of the residuals. Software was also developed to communicate with a Linac and toggle beam delivery. In a separate experiment involving a Linac, 500 monitor units of radiation were delivered to the phantom with a 3 * 3 cm photon beam and with 6 and 10 MV accelerating potential. Radiochromic films were inserted in the phantom to measure spatial dose distribution. In this experiment, the period of motion was set to 60 s to account for beam turn-on latency. The beam was turned off when the marker moved outside of a 5-mm gating window. RESULTS: The precision of the tracking in the IS direction was 0.53 mm for a sinusoidally moving target, with an average count rate ~250 cps. The average prediction error was 1.1 +/- 0.6 mm when the marker moved according to irregular patient breathing motion. Across all beam deliveries during the radiochromic film measurements, the average prediction error was 0.8 +/- 0.5 mm. The maximum error was 2.5 mm and the 95th percentile error was 1.5 mm. Clear improvement of the dose distribution was observed between gated and nongated deliveries. The full-width at halfmaximum of the dose profiles of gated deliveries differed by 3 mm or less than the static reference dose distribution. Monitoring of the beam on/off times showed synchronization with the location of the marker within the latency of the system. CONCLUSIONS: PeTrack can track the motion of internal fiducial positron emission markers with submillimeter precision. The system can be used to gate the delivery of a Linac beam based on the position of a moving fiducial marker. This highlights the potential of the system for use in respiratory-gated radiotherapy. PMID- 26843242 TI - Absolute measurement of LDR brachytherapy source emitted power: Instrument design and initial measurements. AB - PURPOSE: Energy-based source strength metrics may find use with model-based dose calculation algorithms, but no instruments exist that can measure the energy emitted from low-dose rate (LDR) sources. This work developed a calorimetric technique for measuring the power emitted from encapsulated low-dose rate, photon emitting brachytherapy sources. This quantity is called emitted power (EP). The measurement methodology, instrument design and performance, and EP measurements made with the calorimeter are presented in this work. METHODS: A calorimeter operating with a liquid helium thermal sink was developed to measure EP from LDR brachytherapy sources. The calorimeter employed an electrical substitution technique to determine the power emitted from the source. The calorimeter's performance and thermal system were characterized. EP measurements were made using four (125)I sources with air-kerma strengths ranging from 2.3 to 5.6 U and corresponding EPs of 0.39-0.79 MUW, respectively. Three Best Medical 2301 sources and one Oncura 6711 source were measured. EP was also computed by converting measured air-kerma strengths to EPs through Monte Carlo-derived conversion factors. The measured EP and derived EPs were compared to determine the accuracy of the calorimeter measurement technique. RESULTS: The calorimeter had a noise floor of 1-3 nW and a repeatability of 30-60 nW. The calorimeter was stable to within 5 nW over a 12 h measurement window. All measured values agreed with derived EPs to within 10%, with three of the four sources agreeing to within 4%. Calorimeter measurements had uncertainties ranging from 2.6% to 4.5% at the k = 1 level. The values of the derived EPs had uncertainties ranging from 2.9% to 3.6% at the k = 1 level. CONCLUSIONS: A calorimeter capable of measuring the EP from LDR sources has been developed and validated for (125)I sources with EPs between 0.43 and 0.79 MUW. PMID- 26843244 TI - A novel approach to assess the treatment response using Gaussian random field in PET. AB - PURPOSE: The assessment of early therapeutic response to anticancer therapy is vital for treatment planning and patient management in clinic. With the development of personal treatment plan, the early treatment response, especially before any anatomically apparent changes after treatment, becomes urgent need in clinic. Positron emission tomography (PET) imaging serves an important role in clinical oncology for tumor detection, staging, and therapy response assessment. Many studies on therapy response involve interpretation of differences between two PET images, usually in terms of standardized uptake values (SUVs). However, the quantitative accuracy of this measurement is limited. This work proposes a statistically robust approach for therapy response assessment based on Gaussian random field (GRF) to provide a statistically more meaningful scale to evaluate therapy effects. METHODS: The authors propose a new criterion for therapeutic assessment by incorporating image noise into traditional SUV method. An analytical method based on the approximate expressions of the Fisher information matrix was applied to model the variance of individual pixels in reconstructed images. A zero mean unit variance GRF under the null hypothesis (no response to therapy) was obtained by normalizing each pixel of the post-therapy image with the mean and standard deviation of the pretherapy image. The performance of the proposed method was evaluated by Monte Carlo simulation, where XCAT phantoms (128(2) pixels) with lesions of various diameters (2-6 mm), multiple tumor-to background contrasts (3-10), and different changes in intensity (6.25%-30%) were used. The receiver operating characteristic curves and the corresponding areas under the curve were computed for both the proposed method and the traditional methods whose figure of merit is the percentage change of SUVs. The formula for the false positive rate (FPR) estimation was developed for the proposed therapy response assessment utilizing local average method based on random field. The accuracy of the estimation was validated in terms of Euler distance and correlation coefficient. RESULTS: It is shown that the performance of therapy response assessment is significantly improved by the introduction of variance with a higher area under the curve (97.3%) than SUVmean (91.4%) and SUVmax (82.0%). In addition, the FPR estimation serves as a good prediction for the specificity of the proposed method, consistent with simulation outcome with ~1 correlation coefficient. CONCLUSIONS: In this work, the authors developed a method to evaluate therapy response from PET images, which were modeled as Gaussian random field. The digital phantom simulations demonstrated that the proposed method achieved a large reduction in statistical variability through incorporating knowledge of the variance of the original Gaussian random field. The proposed method has the potential to enable prediction of early treatment response and shows promise for application to clinical practice. In future work, the authors will report on the robustness of the estimation theory for application to clinical practice of therapy response evaluation, which pertains to binary discrimination tasks at a fixed location in the image such as detection of small and weak lesion. PMID- 26843243 TI - Attenuation correction in emission tomography using the emission data--A review. AB - The problem of attenuation correction (AC) for quantitative positron emission tomography (PET) had been considered solved to a large extent after the commercial availability of devices combining PET with computed tomography (CT) in 2001; single photon emission computed tomography (SPECT) has seen a similar development. However, stimulated in particular by technical advances toward clinical systems combining PET and magnetic resonance imaging (MRI), research interest in alternative approaches for PET AC has grown substantially in the last years. In this comprehensive literature review, the authors first present theoretical results with relevance to simultaneous reconstruction of attenuation and activity. The authors then look back at the early history of this research area especially in PET; since this history is closely interwoven with that of similar approaches in SPECT, these will also be covered. We then review algorithmic advances in PET, including analytic and iterative algorithms. The analytic approaches are either based on the Helgason-Ludwig data consistency conditions of the Radon transform, or generalizations of John's partial differential equation; with respect to iterative methods, we discuss maximum likelihood reconstruction of attenuation and activity (MLAA), the maximum likelihood attenuation correction factors (MLACF) algorithm, and their offspring. The description of methods is followed by a structured account of applications for simultaneous reconstruction techniques: this discussion covers organ-specific applications, applications specific to PET/MRI, applications using supplemental transmission information, and motion-aware applications. After briefly summarizing SPECT applications, we consider recent developments using emission data other than unscattered photons. In summary, developments using time-of flight (TOF) PET emission data for AC have shown promising advances and open a wide range of applications. These techniques may both remedy deficiencies of purely MRI-based AC approaches in PET/MRI and improve standalone PET imaging. PMID- 26843245 TI - Body-mounted robotic instrument guide for image-guided cryotherapy of renal cancer. AB - PURPOSE: Image-guided cryotherapy of renal cancer is an emerging alternative to surgical nephrectomy, particularly for those who cannot sustain the physical burden of surgery. It is well known that the outcome of this therapy depends on the accurate placement of the cryotherapy probe. Therefore, a robotic instrument guide may help physicians aim the cryotherapy probe precisely to maximize the efficacy of the treatment and avoid damage to critical surrounding structures. The objective of this paper was to propose a robotic instrument guide for orienting cryotherapy probes in image-guided cryotherapy of renal cancers. The authors propose a body-mounted robotic guide that is expected to be less susceptible to guidance errors caused by the patient's whole body motion. METHODS: Keeping the device's minimal footprint in mind, the authors developed and validated a body-mounted, robotic instrument guide that can maintain the geometrical relationship between the device and the patient's body, even in the presence of the patient's frequent body motions. The guide can orient the cryotherapy probe with the skin incision point as the remote-center-of-motion. The authors' validation studies included an evaluation of the mechanical accuracy and position repeatability of the robotic instrument guide. The authors also performed a mock MRI-guided cryotherapy procedure with a phantom to compare the advantage of robotically assisted probe replacements over a free-hand approach, by introducing organ motions to investigate their effects on the accurate placement of the cryotherapy probe. Measurements collected for performance analysis included accuracy and time taken for probe placements. Multivariate analysis was performed to assess if either or both organ motion and the robotic guide impacted these measurements. RESULTS: The mechanical accuracy and position repeatability of the probe placement using the robotic instrument guide were 0.3 and 0.1 mm, respectively, at a depth of 80 mm. The phantom test indicated that the accuracy of probe placement was significantly better with the robotic instrument guide (4.1 mm) than without the guide (6.3 mm, p<0.001), even in the presence of body motion. When independent organ motion was artificially added, in addition to body motion, the advantage of accurate probe placement using the robotic instrument guide disappeared statistically [i.e., 6.0 mm with the robotic guide and 5.9 mm without the robotic guide (p = 0.906)]. When the robotic instrument guide was used, the total time required to complete the procedure was reduced from 19.6 to 12.7 min (p<0.001). Multivariable analysis indicated that the robotic instrument guide, not the organ motion, was the cause of statistical significance. The statistical power the authors obtained was 88% in accuracy assessment and 99% higher in duration measurement. CONCLUSIONS: The body-mounted robotic instrument guide allows positioning of the probe during image-guided cryotherapy of renal cancer and was done in fewer attempts and in less time than the free-hand approach. The accuracy of the placement of the cryotherapy probe was better using the robotic instrument guide than without the guide when no organ motion was present. The accuracy between the robotic and free-hand approach becomes comparable when organ motion was present. PMID- 26843247 TI - Technical Note: Confirming the prescribed angle of CT localizer radiographs and c arm projection acquisitions. AB - PURPOSE: Accurate CT radiograph angle is not usually important in diagnostic CT. However, there are applications in radiation oncology and interventional radiology in which the orientation of the x-ray source and detector with respect to the patient is clinically important. The authors present a method for measuring the accuracy of the tube/detector assembly with respect to the prescribed tube/detector position for CT localizer, fluoroscopic, and general radiograph imaging using diagnostic, mobile, and c-arm based CT systems. METHODS: A mathematical expression relating the x-ray projection of two metal BBs is related to gantry angle. Measurement of the BBs at a prescribed gantry (i.e., c arm) angle can be obtained and using this relation the prescribed versus actual gantry angle compared. No special service mode or proprietary information is required, only access to projection images is required. Projection images are available in CT via CT localizer radiographs and in the interventional setting via fluorography. RESULTS: The technique was demonstrated on two systems, a mobile CT scanner and a diagnostic CT scanner. The results confirmed a known issue with the mobile scanner and accurately described the CT localizer angle of the diagnostic system tested. CONCLUSIONS: This method can be used to quantify gantry angle, which is important when projection images are used for procedure guidance, such as in brachytherapy and interventional radiology applications. PMID- 26843246 TI - A novel perfused Bloch-McConnell simulator for analyzing the accuracy of dynamic hyperpolarized MRS. AB - PURPOSE: Magnetic resonance spectroscopy of hyperpolarized agents allows real time detection of metabolism in vivo. However, the nonrenewable nature of these signals necessitates data acquisitions that differ significantly from conventional magnetic resonance imaging. Signal evolution is permanently altered by the data acquisition scheme, potentially leading to sequence parameter dependent bias in quantification. The authors have developed a novel simulation environment to characterize the effects of sequence parameters on magnetic resonance spectroscopy-based chemical exchange measurements using hyperpolarized pyruvate. METHODS: Conventional Bloch-McConnell equations were coupled with a pharmacokinetic model for perfusion to allow realistic simulation of in vivo dynamic hyperpolarized signal evolution. In this study, simulations were conducted to explore effects of excitation angle and repetition time on the observed signal and subsequent parametric analysis. Both high and low apparent exchange rates were modeled under assumption of both perfused and closed systems. Bias due to sampling strategy bias was subsequently tested in vivo. RESULTS: Simulation of dynamic magnetic resonance spectroscopy studies using hyperpolarized pyruvate demonstrated that for closed systems, accurate measurement of the apparent exchange rate was possible over a wide range of sequence parameters. This was true for both high and low apparent exchange rates, although a low exchange rate was associated with larger errors when excitation angles were high. When effects of perfusion were included to account for pyruvate delivery, a more restricted range of settings led to accurate quantification of exchange rates. Perfusion alleviated some of the errors seen at high excitation angles for low exchange rates. Residuals from parametric analysis did not generally correlate with fit accuracy, implying that the quality of the analysis model was not a major driver of error. Animal studies acquired with sequence parameters that are predicted to impart bias showed a significant under estimation of exchange rates (P < 0.035) compared to parameter combinations that are not expected to bias measurements. CONCLUSIONS: The authors' results suggest that great care must be taken when measuring dynamic processes by magnetic resonance spectroscopy of hyperpolarized substrates. When comparing apparent exchange rates, choice of sequence parameters will affect the results. Bias introduced by parameters of more advanced acquisition and reconstruction schemes will likely increase compared to the relatively simple dynamic spectroscopy methods tested herein. The modified Bloch-McConnell equations the authors describe will be crucial tools for characterizing and optimizing the performance of these more advanced techniques. PMID- 26843249 TI - Coping with real world data: Artifact reduction and denoising for motion compensated cardiac C-arm CT. AB - PURPOSE: Detailed analysis of cardiac motion would be helpful for supporting clinical workflow in the interventional suite. With an angiographic C-arm system, multiple heart phases can be reconstructed using electrocardiogram gating. However, the resulting angular undersampling is highly detrimental to the quality of the reconstructed images, especially in nonideal intraprocedural imaging conditions. Motion-compensated reconstruction has previously been shown to alleviate this problem, but it heavily relies on a preliminary reconstruction suitable for motion estimation. In this work, the authors propose a processing pipeline tailored to augment these initial images for the purpose of motion estimation and assess how it affects the final images after motion compensation. METHODS: The following combination of simple, direct methods inspired by the core ideas of existing approaches proved beneficial: (a) Streak reduction by masking high-intensity components in projection domain after filtering. (b) Streak reduction by subtraction of estimated artifact volumes in reconstruction domain. (c) Denoising in spatial domain using a joint bilateral filter guided by an uncompensated reconstruction. (d) Denoising in temporal domain using an adaptive Gaussian smoothing based on a novel motion detection scheme. RESULTS: Experiments on a numerical heart phantom yield a reduction of the relative root-mean-square error from 89.9% to 3.6% and an increase of correlation with the ground truth from 95.763% to 99.995% for the motion-compensated reconstruction when the authors' processing is applied to the initial images. In three clinical patient data sets, the signal-to-noise ratio measured in an ideally homogeneous region is increased by 37.7% on average. Overall visual appearance is improved notably and some anatomical features are more readily discernible. CONCLUSIONS: The authors' findings suggest that the proposed sequence of steps provides a clear advantage over an arbitrary sequence of individual image enhancement methods and is fit to overcome the issue of lacking image quality in motion-compensated C-arm imaging of the heart. As for future work, the obtained results pave the way for investigating how accurately cardiac functional motion parameters can be determined with this modality. PMID- 26843248 TI - Nonthermal ablation of deep brain targets: A simulation study on a large animal model. AB - PURPOSE: Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is currently limited to central brain targets because of heating and other beam effects caused by the presence of the skull. Recently, it was shown that it is possible to ablate tissues without depositing thermal energy by driving intravenously administered microbubbles to inertial cavitation using low-duty cycle burst sonications. A recent study demonstrated that this ablation method could ablate tissue volumes near the skull base in nonhuman primates without thermally damaging the nearby bone. However, blood-brain disruption was observed in the prefocal region, and in some cases, this region contained small areas of tissue damage. The objective of this study was to analyze the experimental model with simulations and to interpret the cause of these effects. METHODS: The authors simulated prior experiments where nonthermal ablation was performed in the brain in anesthetized rhesus macaques using a 220 kHz clinical prototype transcranial MRI-guided FUS system. Low-duty-cycle sonications were applied at deep brain targets with the ultrasound contrast agent Definity. For simulations, a 3D pseudospectral finite difference time domain tool was used. The effects of shear mode conversion, focal steering, skull aberrations, nonlinear propagation, and the presence of skull base on the pressure field were investigated using acoustic and elastic wave propagation models. RESULTS: The simulation results were in agreement with the experimental findings in the prefocal region. In the postfocal region, however, side lobes were predicted by the simulations, but no effects were evident in the experiments. The main beam was not affected by the different simulated scenarios except for a shift of about 1 mm in peak position due to skull aberrations. However, the authors observed differences in the volume, amplitude, and distribution of the side lobes. In the experiments, a single element passive cavitation detector was used to measure the inertial cavitation threshold and to determine the pressure amplitude to use for ablation. Simulations of the detector's acoustic field suggest that its maximum sensitivity was in the lower part of the main beam, which may have led to excessive exposure levels in the experiments that may have contributed to damage in the prefocal area. CONCLUSIONS: Overall, these results suggest that case-specific full wave simulations before the procedure can be useful to predict the focal and the prefocal side lobes and the extent of the resulting bioeffects produced by nonthermal ablation. Such simulations can also be used to optimally position passive cavitation detectors. The disagreement between the simulations and the experiments in the postfocal region may have been due to shielding of the ultrasound field due to microbubble activity in the focal region. Future efforts should include the effects of microbubble activity and vascularization on the pressure field. PMID- 26843250 TI - Evaluation of a commercial MRI Linac based Monte Carlo dose calculation algorithm with GEANT4. AB - PURPOSE: This paper provides a comparison between a fast, commercial, in-patient Monte Carlo dose calculation algorithm (GPUMCD) and geant4. It also evaluates the dosimetric impact of the application of an external 1.5 T magnetic field. METHODS: A stand-alone version of the ElektaTM GPUMCD algorithm, to be used within the Monaco treatment planning system to model dose for the ElektaTM magnetic resonance imaging (MRI) Linac, was compared against GEANT4 (v10.1). This was done in the presence or absence of a 1.5 T static magnetic field directed orthogonally to the radiation beam axis. Phantoms with material compositions of water, ICRU lung, ICRU compact-bone, and titanium were used for this purpose. Beams with 2 MeV monoenergetic photons as well as a 7 MV histogrammed spectrum representing the MRI Linac spectrum were emitted from a point source using a nominal source-to-surface distance of 142.5 cm. Field sizes ranged from 1.5 * 1.5 to 10 * 10 cm(2). Dose scoring was performed using a 3D grid comprising 1 mm(3) voxels. The production thresholds were equivalent for both codes. Results were analyzed based upon a voxel by voxel dose difference between the two codes and also using a volumetric gamma analysis. RESULTS: Comparisons were drawn from central axis depth doses, cross beam profiles, and isodose contours. Both in the presence and absence of a 1.5 T static magnetic field the relative differences in doses scored along the beam central axis were less than 1% for the homogeneous water phantom and all results matched within a maximum of +/-2% for heterogeneous phantoms. Volumetric gamma analysis indicated that more than 99% of the examined volume passed gamma criteria of 2%-2 mm (dose difference and distance to agreement, respectively). These criteria were chosen because the minimum primary statistical uncertainty in dose scoring voxels was 0.5%. The presence of the magnetic field affects the dose at the interface depending upon the density of the material on either sides of the interface. This effect varies with the field size. For example, at the water-lung interface a 33.94% increase in dose was observed (relative to the Dmax), by both GPUMCD and GEANT4 for the field size of 2 * 2 cm(2) (compared to no B-field case), which increased to 47.83% for the field size of 5 * 5 cm(2) in the presence of the magnetic field. Similarly, at the lung-water interface, the dose decreased by 19.21% (relative to Dmax) for a field size of 2 * 2 cm(2) and by 30.01% for 5 * 5 cm(2) field size. For more complex combinations of materials the dose deposition also becomes more complex. CONCLUSIONS: The GPUMCD algorithm showed good agreement against GEANT4 both in the presence and absence of a 1.5 T external magnetic field. The application of 1.5 T magnetic field significantly alters the dose at the interfaces by either increasing or decreasing the dose depending upon the density of the material on either side of the interfaces. PMID- 26843251 TI - Technical Note: Radiological properties of tissue surrogates used in a multimodality deformable pelvic phantom for MR-guided radiotherapy. AB - PURPOSE: Phantom surrogates were developed to allow multimodal [computed tomography (CT), magnetic resonance imaging (MRI), and teletherapy] and anthropomorphic tissue simulation as well as materials and methods to construct deformable organ shapes and anthropomorphic bone models. METHODS: Agarose gels of variable concentrations and loadings were investigated to simulate various soft tissue types. Oils, fats, and Vaseline were investigated as surrogates for adipose tissue and bone marrow. Anthropomorphic shapes of bone and organs were realized using 3D-printing techniques based on segmentations of patient CT-scans. All materials were characterized in dual energy CT and MRI to adapt CT numbers, electron density, effective atomic number, as well as T1- and T2-relaxation times to patient and literature values. RESULTS: Soft tissue simulation could be achieved with agarose gels in combination with a gadolinium-based contrast agent and NaF to simulate muscle, prostate, and tumor tissues. Vegetable oils were shown to be a good representation for adipose tissue in all modalities. Inner bone was realized using a mixture of Vaseline and K2HPO4, resulting in both a fatty bone marrow signal in MRI and inhomogeneous areas of low and high attenuation in CT. The high attenuation of outer bone was additionally adapted by applying gypsum bandages to the 3D-printed hollow bone case with values up to 1200 HU. Deformable hollow organs were manufactured using silicone. Signal loss in the MR images based on the conductivity of the gels needs to be further investigated. CONCLUSIONS: The presented surrogates and techniques allow the customized construction of multimodality, anthropomorphic, and deformable phantoms as exemplarily shown for a pelvic phantom, which is intended to study adaptive treatment scenarios in MR-guided radiation therapy. PMID- 26843252 TI - A novel software and conceptual design of the hardware platform for intensity modulated radiation therapy. AB - PURPOSE: To deliver high quality intensity modulated radiotherapy (IMRT) using a novel generalized sparse orthogonal collimators (SOCs), the authors introduce a novel direct aperture optimization (DAO) approach based on discrete rectangular representation. METHODS: A total of seven patients-two glioblastoma multiforme, three head & neck (including one with three prescription doses), and two lung were included. 20 noncoplanar beams were selected using a column generation and pricing optimization method. The SOC is a generalized conventional orthogonal collimators with N leaves in each collimator bank, where N = 1, 2, or 4. SOC degenerates to conventional jaws when N = 1. For SOC-based IMRT, rectangular aperture optimization (RAO) was performed to optimize the fluence maps using rectangular representation, producing fluence maps that can be directly converted into a set of deliverable rectangular apertures. In order to optimize the dose distribution and minimize the number of apertures used, the overall objective was formulated to incorporate an L2 penalty reflecting the difference between the prescription and the projected doses, and an L1 sparsity regularization term to encourage a low number of nonzero rectangular basis coefficients. The optimization problem was solved using the Chambolle-Pock algorithm, a first-order primal-dual algorithm. Performance of RAO was compared to conventional two-step IMRT optimization including fluence map optimization and direct stratification for multileaf collimator (MLC) segmentation (DMS) using the same number of segments. For the RAO plans, segment travel time for SOC delivery was evaluated for the N = 1, N = 2, and N = 4 SOC designs to characterize the improvement in delivery efficiency as a function of N. RESULTS: Comparable PTV dose homogeneity and coverage were observed between the RAO and the DMS plans. The RAO plans were slightly superior to the DMS plans in sparing critical structures. On average, the maximum and mean critical organ doses were reduced by 1.94% and 1.44% of the prescription dose. The average number of delivery segments was 12.68 segments per beam for both the RAO and DMS plans. The N = 2 and N = 4 SOC designs were, on average, 1.56 and 1.80 times more efficient than the N = 1 SOC design to deliver. The mean aperture size produced by the RAO plans was 3.9 times larger than that of the DMS plans. CONCLUSIONS: The DAO and dose domain optimization approach enabled high quality IMRT plans using a low-complexity collimator setup. The dosimetric quality is comparable or slightly superior to conventional MLC-based IMRT plans using the same number of delivery segments. The SOC IMRT delivery efficiency can be significantly improved by increasing the leaf numbers, but the number is still significantly lower than the number of leaves in a typical MLC. PMID- 26843253 TI - Optimization of oncological 18F-FDG PET/CT imaging based on a multiparameter analysis. AB - PURPOSE: This paper describes a method to achieve consistent clinical image quality in (18)F-FDG scans accounting for patient habitus, dose regimen, image acquisition, and processing techniques. METHODS: Oncological PET/CT scan data for 58 subjects were evaluated retrospectively to derive analytical curves that predict image quality. Patient noise equivalent count rate and coefficient of variation (CV) were used as metrics in their analysis. Optimized acquisition protocols were identified and prospectively applied to 179 subjects. RESULTS: The adoption of different schemes for three body mass ranges (<60 kg, 60-90 kg, >90 kg) allows improved image quality with both point spread function and ordered subsets expectation maximization-3D reconstruction methods. The application of this methodology showed that CV improved significantly (p < 0.0001) in clinical practice. CONCLUSIONS: Consistent oncological PET/CT image quality on a high performance scanner was achieved from an analysis of the relations existing between dose regimen, patient habitus, acquisition, and processing techniques. The proposed methodology may be used by PET/CT centers to develop protocols to standardize PET/CT imaging procedures and achieve better patient management and cost-effective operations. PMID- 26843255 TI - An ellipsoid convex enhancement filter for detection of asymptomatic intracranial aneurysm candidates in CAD frameworks. AB - PURPOSE: Various kinds of enhancement filters have been developed in computer aided diagnostic (CAD) frameworks for asymptomatic intracranial aneurysms in magnetic resonance angiography (MRA). However, many bending or branching portions on vessels are also enhanced by the conventional filters as false positives in 3.0 T MRA, which can visualize smaller vessels compared with 1.5 T MRA. To overcome this problem, this study focused on developing an ellipsoid convex enhancement (ECE) filter, which can selectively enhance aneurysms while reducing false positive contrasts on bending or branching portions on vessels, for detection of asymptomatic intracranial aneurysm candidates in CAD frameworks. METHODS: The ECE filter was mathematically designed to enhance various convex regions in the intensity space such as convex aneurysms, in which the ratio of the shortest and longest diameters for aneurysms corresponds to the ratio of reciprocals of the square roots of the first and third eigenvalues of a Hessian matrix. The proposed ECE filter was evaluated by measuring an average contrast for false positive models and free-response receiver operating characteristic curves between two simple CAD frameworks using the ECE and conventional filters based on a leave-one-out-by-patient test. MRA images for thirty patients (male: 10, female: 20; age: 48-86 yr, mean: 69.2) with 31 unruptured aneurysms (longest diameter: 2.0-5.5 mm, mean: 3.7 mm) were selected for this study. RESULTS: The average contrast for false positive models was reduced by 51.4% using the ECE filter, compared with the conventional filter for the convex regions with ratios of the shortest and longest diameters less than 0.4. The number of false positives per case was decreased from 41.1 to 22.8 on average at a sensitivity of 87% by using the ECE filter. CONCLUSIONS: The ECE filter would be useful for boosting the performance of the CAD framework of asymptomatic intracranial aneurysms by providing higher contrast aneurysms and lower contrast false positives such as bending or branching portions on vessels. PMID- 26843254 TI - A combined time-of-flight and depth-of-interaction detector for total-body positron emission tomography. AB - PURPOSE: In support of a project to build a total-body PET scanner with an axial field-of-view of 2 m, the authors are developing simple, cost-effective block detectors with combined time-of-flight (TOF) and depth-of-interaction (DOI) capabilities. METHODS: This work focuses on investigating the potential of phosphor-coated crystals with conventional PMT-based block detector readout to provide DOI information while preserving timing resolution. The authors explored a variety of phosphor-coating configurations with single crystals and crystal arrays. Several pulse shape discrimination techniques were investigated, including decay time, delayed charge integration (DCI), and average signal shapes. RESULTS: Pulse shape discrimination based on DCI provided the lowest DOI positioning error: 2 mm DOI positioning error was obtained with single phosphor coated crystals while 3-3.5 mm DOI error was measured with the block detector module. Minimal timing resolution degradation was observed with single phosphor coated crystals compared to uncoated crystals, and a timing resolution of 442 ps was obtained with phosphor-coated crystals in the block detector compared to 404 ps without phosphor coating. Flood maps showed a slight degradation in crystal resolvability with phosphor-coated crystals; however, all crystals could be resolved. Energy resolution was degraded by 3%-7% with phosphor-coated crystals compared to uncoated crystals. CONCLUSIONS: These results demonstrate the feasibility of obtaining TOF-DOI capabilities with simple block detector readout using phosphor-coated crystals. PMID- 26843256 TI - An online x-ray based position validation system for prostate hypofractionated radiotherapy. AB - PURPOSE: Accurate positioning of the target volume during treatment is paramount for stereotactic body radiation therapy (SBRT). In this work, the authors present the development of an in-house software tool to verify target position with an Elekta-Synergy linear accelerator using kV planar images acquired during treatment delivery. METHODS: In-house software, SeedTracker, was developed in matlab to perform the following three functions: 1. predict intended seed positions in a planar view perpendicular to any gantry angle, simulating a portal imaging device, from the 3D seed co-ordinates derived from the treatment planning system; 2. autosegment seed positions in kV planar images; and 3. report the position shift based on the seed positions in the projection images. The performance of SeedTracker was verified using a CIRS humanoid phantom (CIRS, VA, USA) implanted with three Civco gold seed markers (Civco, IA, USA) in the prostate. The true positive rate of autosegmentation (TPRseg) and the accuracy of the software in alerting the user when the isocenter position was outside the tolerance (TPRtrig) were studied. Two-dimensional and 3D static position offsets introduced to the humanoid phantom and 3D dynamic offsets introduced to a gel phantom containing gold seeds were used for evaluation of the system. RESULTS: SeedTracker showed a TPRseg of 100% in the humanoid phantom for projection images acquired at all angles except in the ranges of 80 degrees -100 degrees and 260 degrees -280 degrees where seeds are obscured by anatomy. This resulted in a TPRtrig of 88% over the entire treatment range for considered 3D static offsets introduced to the phantom. For 2D static offsets where the position offsets were only introduced in the anterior-posterior and lateral directions, the TPRtrig of SeedTracker was limited by both seed detectability and positional offset. SeedTracker showed a false positive trigger in the projection angle range between 130 degrees -170 degrees and 310 degrees -350 degrees (a maximum of 24% of treatment time) due to limited information that can be derived from monoscopic images. The system accurately determined the dynamic trajectory of the isocenter position in the superior and inferior direction for the studied dynamic offset scenarios based on the seed position in monoscopic images. CONCLUSIONS: The developed software has been shown to accurately autosegment the seed positions in kV planar images except for two 20 degrees arcs where seeds are obscured by anatomical structures. The isocenter trajectories determined by the system, based on the monoscopic images, provide useful information for monitoring the prostate position. The developed system has potential application for monitoring prostate position during treatment delivery in linear accelerator based SBRT. PMID- 26843257 TI - Initial clinical evaluation of PET-based ion beam therapy monitoring under consideration of organ motion. AB - PURPOSE: Intrafractional organ motion imposes considerable challenges to scanned ion beam therapy and demands for a thorough verification of the applied treatment. At the Heidelberg Ion-Beam Therapy Center (HIT), the scanned ion beam delivery is verified by means of postirradiation positron-emission-tomography (PET) imaging. This work presents a first clinical evaluation of PET-based treatment monitoring in ion beam therapy under consideration of target motion. METHODS: Three patients with mobile liver lesions underwent scanned carbon ion irradiation at HIT and postirradiation PET/CT (x-ray-computed-tomography) imaging with a commercial scanner. Respiratory motion was recorded during irradiation and subsequent image acquisition. This enabled a time-resolved (4D) calculation of the expected irradiation-induced activity pattern and, for one patient where an additional 4D CT was acquired at the PET/CT scanner after treatment, a motion compensated PET image reconstruction. For the other patients, PET data were reconstructed statically. To verify the treatment, calculated prediction and reconstructed measurement were compared with a focus on the ion beam range. RESULTS: Results in the current three patients suggest that for motion amplitudes in the order of 2 mm there is no benefit from incorporating respiratory motion information into PET-based treatment monitoring. For a target motion in the order of 10 mm, motion-related effects become more severe and a time-resolved modeling of the expected activity distribution can lead to an improved data interpretation if a sufficient number of true coincidences is detected. Benefits from motion compensated PET image reconstruction could not be shown conclusively at the current stage. CONCLUSIONS: The feasibility of clinical PET-based treatment verification under consideration of organ motion has been shown for the first time. Improvements in noise-robust 4D PET image reconstruction are deemed necessary to enhance the clinical potential. PMID- 26843258 TI - Technical Note: Independent component analysis for quality assurance in functional MRI. AB - PURPOSE: Independent component analysis (ICA) is an established method of analyzing human functional MRI (fMRI) data. Here, an ICA-based fMRI quality control (QC) tool was developed and used. METHODS: ICA-based fMRI QC tool to be used with a commercial phantom was developed. In an attempt to assess the performance of the tool relative to preexisting alternative tools, it was used seven weeks before and eight weeks after repair of a faulty gradient amplifier of a non-state-of-the-art MRI unit. More specifically, its performance was compared with the AAPM 100 acceptance testing and quality assurance protocol and two fMRI QC protocols, proposed by Freidman et al. ["Report on a multicenter fMRI quality assurance protocol," J. Magn. Reson. Imaging 23, 827-839 (2006)] and Stocker et al. ["Automated quality assurance routines for fMRI data applied to a multicenter study," Hum. Brain Mapp. 25, 237-246 (2005)], respectively. RESULTS: The easily developed and applied ICA-based QC protocol provided fMRI QC indices and maps equally sensitive to fMRI instabilities with the indices and maps of other established protocols. The ICA fMRI QC indices were highly correlated with indices of other fMRI QC protocols and in some cases theoretically related to them. Three or four independent components with slow varying time series are detected under normal conditions. CONCLUSIONS: ICA applied on phantom measurements is an easy and efficient tool for fMRI QC. Additionally, it can protect against misinterpretations of artifact components as human brain activations. Evaluating fMRI QC indices in the central region of a phantom is not always the optimal choice. PMID- 26843259 TI - Cherenkov imaging method for rapid optimization of clinical treatment geometry in total skin electron beam therapy. AB - PURPOSE: A method was developed utilizing Cherenkov imaging for rapid and thorough determination of the two gantry angles that produce the most uniform treatment plane during dual-field total skin electron beam therapy (TSET). METHODS: Cherenkov imaging was implemented to gather 2D measurements of relative surface dose from 6 MeV electron beams on a white polyethylene sheet. An intensified charge-coupled device camera time-gated to the Linac was used for Cherenkov emission imaging at sixty-two different gantry angles (1 degrees increments, from 239.5 degrees to 300.5 degrees ). Following a modified Stanford TSET technique, which uses two fields per patient position for full body coverage, composite images were created as the sum of two beam images on the sheet; each angle pair was evaluated for minimum variation across the patient region of interest. Cherenkov versus dose correlation was verified with ionization chamber measurements. The process was repeated at source to surface distance (SSD) = 441, 370.5, and 300 cm to determine optimal angle spread for varying room geometries. In addition, three patients receiving TSET using a modified Stanford six-dual field technique with 6 MeV electron beams at SSD = 441 cm were imaged during treatment. RESULTS: As in previous studies, Cherenkov intensity was shown to directly correlate with dose for homogenous flat phantoms (R(2) = 0.93), making Cherenkov imaging an appropriate candidate to assess and optimize TSET setup geometry. This method provided dense 2D images allowing 1891 possible treatment geometries to be comprehensively analyzed from one data set of 62 single images. Gantry angles historically used for TSET at their institution were 255.5 degrees and 284.5 degrees at SSD = 441 cm; however, the angles optimized for maximum homogeneity were found to be 252.5 degrees and 287.5 degrees (+6 degrees increase in angle spread). Ionization chamber measurements confirmed improvement in dose homogeneity across the treatment field from a range of 24.4% at the initial angles, to only 9.8% with the angles optimized. A linear relationship between angle spread and SSD was observed, ranging from 35 degrees at 441 cm, to 39 degrees at 300 cm, with no significant variation in percent depth dose at midline (R(2) = 0.998). For patient studies, factors influencing in vivo correlation between Cherenkov intensity and measured surface dose are still being investigated. CONCLUSIONS: Cherenkov intensity correlates to relative dose measured at depth of maximum dose in a uniform, flat phantom. Imaging of phantoms can thus be used to analyze and optimize TSET treatment geometry more extensively and rapidly than thermoluminescent dosimeters or ionization chambers. This work suggests that there could be an expanded role for Cherenkov imaging as a tool to efficiently improve treatment protocols and as a potential verification tool for routine monitoring of unique patient treatments. PMID- 26843261 TI - Erratum: "Calculation of dose distributions for 12 106Ru/106Rh ophthalmic applicator models with the penelope Monte Carlo code" [Med. Phys. 40, 101705 (13pp.) (2013)]. PMID- 26843260 TI - Nonlocal atlas-guided multi-channel forest learning for human brain labeling. AB - PURPOSE: It is important for many quantitative brain studies to label meaningful anatomical regions in MR brain images. However, due to high complexity of brain structures and ambiguous boundaries between different anatomical regions, the anatomical labeling of MR brain images is still quite a challenging task. In many existing label fusion methods, appearance information is widely used. However, since local anatomy in the human brain is often complex, the appearance information alone is limited in characterizing each image point, especially for identifying the same anatomical structure across different subjects. Recent progress in computer vision suggests that the context features can be very useful in identifying an object from a complex scene. In light of this, the authors propose a novel learning-based label fusion method by using both low-level appearance features (computed from the target image) and high-level context features (computed from warped atlases or tentative labeling maps of the target image). METHODS: In particular, the authors employ a multi-channel random forest to learn the nonlinear relationship between these hybrid features and target labels (i.e., corresponding to certain anatomical structures). Specifically, at each of the iterations, the random forest will output tentative labeling maps of the target image, from which the authors compute spatial label context features and then use in combination with original appearance features of the target image to refine the labeling. Moreover, to accommodate the high inter-subject variations, the authors further extend their learning-based label fusion to a multi-atlas scenario, i.e., they train a random forest for each atlas and then obtain the final labeling result according to the consensus of results from all atlases. RESULTS: The authors have comprehensively evaluated their method on both public LONI_LBPA40 and IXI datasets. To quantitatively evaluate the labeling accuracy, the authors use the dice similarity coefficient to measure the overlap degree. Their method achieves average overlaps of 82.56% on 54 regions of interest (ROIs) and 79.78% on 80 ROIs, respectively, which significantly outperform the baseline method (random forests), with the average overlaps of 72.48% on 54 ROIs and 72.09% on 80 ROIs, respectively. CONCLUSIONS: The proposed methods have achieved the highest labeling accuracy, compared to several state-of the-art methods in the literature. PMID- 26843262 TI - Characterization of the chemical composition of white chrysanthemum flowers of Hangzhou by using high-performance ion trap mass spectrometry. AB - In this study, high-performance liquid chromatography coupled with amaZon SL high performance ion trap mass spectrometry was used to analyze the target components in white chrysanthemum flowers of Hangzhou. Twenty-one components were detected and identified in both white chrysanthemum flowers of Hangzhou samples by using target compound analysis. Furthermore, seven new compounds in white chrysanthemum flowers of Hangzhou were found and identified by analyzing the fragment ion behavior in the mass spectra. The established method can be expedient for the global quality investigation of complex components in herbal medicines and food. PMID- 26843263 TI - The free fasciocutaneous infragluteal (FCI) flap: Outcome and patient satisfaction after 142 breast reconstructions. AB - BACKGROUND: The free fasciocutaneous infragluteal flap (FCI) is relatively rarely used for autologous breast reconstruction; however, it is a good option for thin patients. The outcome of 142 FCI flaps for breast reconstruction is presented here. MATERIALS AND METHODS: Between January 2008 and December 2013, 142 patients underwent unilateral breast reconstruction with the FCI flap. Outcome analysis, scar quality, postoperative pain, and patient satisfaction were evaluated by questionnaires and established scores. The tactile sensitivity of the breast was measured by the Semmes-Weinstein monofilament test. RESULTS: The mean age was 45.4 +/- 9.17 (23-69) years, the mean follow-up was 40.2 (12-58) months, and the rate of flap loss was 0.7% (n = 1). Postoperative pain was stated with 4.2 +/- 2.5 points on the visual analog scale (VAS). The quality of breast reconstruction was rated "very good" (n = 43) or "good" (n = 33) by 71% of patients, and 89% (n = 96) of patients would recommend this procedure to others. As expected, postoperative mobility was achieved in 80% (n = 86) of patients and some obtained this even earlier. Forty-seven patients presented for follow-up examination (44%). Scars on the reconstructed breasts were rated with 1 (n = 16) or 2 (n = 22) points in 81% and scars at the infragluteal donor site with 2 (n = 17) or 3 (n = 25) points on the Vancouver scar scale (VSS) in 89%. Patients subjectively stated having better sensitivity of the reconstructed breast than measured objectively by monofilaments. CONCLUSION: The FCI flap is a safe method for breast reconstruction due to a low percentage of flap loss and complications. Good patient satisfaction along with fast postoperative mobilization can be achieved. The FCI flap should be considered a suitable alternative for autologous breast reconstruction. PMID- 26843264 TI - Reply: Treatment of hydrofluoric acid burns of the fingers. PMID- 26843265 TI - Treatment of compound tibia fracture with microvascular latissimus dorsi flap and the Ilizarov technique: A cross-sectional study of long-term outcomes. AB - BACKGROUND: Extensive compound tibial fractures present reconstructive challenges. The present study aimed to assess the outcomes of microvascular latissimus dorsi (LD) flap combined with the Ilizarov technique for extensive compound tibial fractures with bone loss and bone healing complications. METHODS: Patient records were reviewed retrospectively. The Lower Extremity Functional Scale (LEFS), the Disabilities of the Arm, Hand and Shoulder (DASH), and the 15D health-related quality of life (HRQoL) instrument were applied. RESULTS: Between 1989 and 2014, 16 patients underwent reconstruction with a microvascular LD flap and bone transport (11/16) or late bone lengthening (5/16). The mean clinical follow-up time was 6.6 (standard deviation (SD): 6.5) years. Three patients had minor complications requiring reoperation. Partial necrosis of one flap required late flap reconstruction in one case. Late bone grafting was used to enhance union in eight of 16 cases. The mean new bone gain was 3.8 cm (SD: 2.5). Overall, 11 patients completed the questionnaires in a mean of 22.3 years (SD: 2.4) after surgery. The main findings revealed a relatively good function of the reconstructed limb and good shoulder function. The mean HRQoL was comparable to that of an age-standardized sample of the general population. CONCLUSION: Segmental tibia transport and lengthening to correct limb length discrepancy do not compromise the microvascular muscle flap. Combined microvascular LD flap reconstruction and the Ilizarov technique can be used in treating acute compound tibial defects, pseudoarthrosis, and osteitis, all associated with significant amputation risk. Fair long-term functional outcomes and HRQoL are achieved when these combined techniques are used. PMID- 26843266 TI - Impact of Imatinib Adherence on the Cytogenetic Response in Pediatric Chronic Myeloid Leukemia - Chronic Phase. AB - The authors aimed to study the impact of adherence to imatinib during initial 6 mo on the cytogenetic response in pediatric chronic myeloid leukemia - chronic phase (CML CP). The hospital records of pediatric CML patients (age <=18 y) from 2009 through 2012, were analyzed retrospectively for the drug adherence and cytogenetic response (CyR) at 6 mo. Forty eight children were analyzed, with the median age of 13 y (range 5-18) and slight male preponderance (M:F- 1.18:1). Sokal scores were low, intermediate and high in 14 (29.3 %), 26 (54.1 %), 8 (16.6 %) children respectively. Only a little more than half of the children were adherent (58 %). At the end of 6 mo, complete cytogenetic response (CCyR) was achieved by 78.5 % of adherent children as compared to 5 % of non-adherent children. Majority (80 %) of the non-adherent children had only a partial cytogenetic response (PCyR). Therefore, it is concluded that most of the adherent children had optimal cytogenetic response at the end of 6 mo and majority of those in the non-adherent group did not attain it. PMID- 26843267 TI - Metabolic Interactions Between Various Micronutrients. PMID- 26843268 TI - Mark Porter: A covert petrolhead. PMID- 26843269 TI - Evolutionary aspects of plant photoreceptors. AB - Plant photoreceptors link environmental light cues with physiological responses, determining how individual plants complete their life cycles. Structural and functional evolution of photoreceptors has co-occurred as plants diversified and faced the challenge of new light environments, during the transition of plants to land and as substantial plant canopies evolved. Large-scale comparative sequencing projects allow us for the first time to document photoreceptor evolution in understudied clades, revealing some surprises. Here we review recent progress in evolutionary studies of three photoreceptor families: phytochromes, phototropins and neochromes. PMID- 26843271 TI - International Consensus on Key Concepts and Data Definitions for Mass-gathering Health: Process and Progress. AB - Mass gatherings (MGs) occur worldwide on any given day, yet mass-gathering health (MGH) is a relatively new field of scientific inquiry. As the science underpinning the study of MGH continues to develop, there will be increasing opportunities to improve health and safety of those attending events. The emerging body of MG literature demonstrates considerable variation in the collection and reporting of data. This complicates comparison across settings and limits the value and utility of these reported data. Standardization of data points and/or reporting in relation to events would aid in creating a robust evidence base from which governments, researchers, clinicians, and event planners could benefit. Moving towards international consensus on any topic is a complex undertaking. This report describes a collaborative initiative to develop consensus on key concepts and data definitions for a MGH "Minimum Data Set." This report makes transparent the process undertaken, demonstrates a pragmatic way of managing international collaboration, and proposes a number of steps for progressing international consensus. The process included correspondence through a journal, face-to-face meetings at a conference, then a four-day working meeting; virtual meetings over a two-year period supported by online project management tools; consultation with an international group of MGH researchers via an online Delphi process; and a workshop delivered at the 19thWorld Congress on Disaster and Emergency Medicine held in Cape Town, South Africa in April 2015. This resulted in an agreement by workshop participants that there is a need for international consensus on key concepts and data definitions. PMID- 26843270 TI - Home management of INR in the public health system: feasibility of self management of oral anticoagulation and long-term performance of individual POC devices in determining INR. AB - The home prothrombin time/international normalized ratio (PT/INR) self-management could be convenient for patients, enhancing treatment compliance and improving the quality of the oral anticoagulation. However, patient self-management (PSM) of oral anticoagulation may not be feasible for up to half of the patients due to cognitive or educational issues. In the present study, we aimed to evaluate the feasibility of a PSM program in a public health medical center that provides care for low-income patients. We also aimed to determine the accuracy of individual point-of-care devices (CoaguChek XS((r))) during long-term of home manipulation. Patients' time-in-therapeutic range (TTR) and perception of quality of life, were evaluated at scheduled study-visits to the center. Additionally, the accuracy of individual CoaguChek XS((r)) was evaluated in comparison to the standard automated coagulometer at scheduled study-visits to the center. Twenty-five patients were included in the PSM program. The median TTR of patients was 75 % before inclusion, 72 % at 3 months, 75 % at 6 months and 100 % at 12 months after the beginning of self-management (P = 0.14).The median DASS scores were 64, 63, 61.5 and 71.5 before inclusion and at 3, 6 and 12 months, respectively (P = 0.09). One hundred paired INR values were obtained. Correlation between INR values delivered by individual CoaguChek XS((r)) and the automated coagulometer was 94 % and the mean result bias was 0.07 INR units. The coefficient of correlation and the mean bias between methods was stable during 24 months of follow-up. The present study suggests that PSM is feasible for patients treated in the public health system and that the results delivered by CoaguChek XS((r)) have long-term reliability. PMID- 26843273 TI - C1q/TNF-related protein 1: a novel link between visceral fat and athero inflammation. PMID- 26843272 TI - Multifaceted intervention including education, rounding checklist implementation, cost feedback, and financial incentives reduces inpatient laboratory costs. AB - BACKGROUND: Inappropriate laboratory testing is a contributor to waste in healthcare. OBJECTIVE: To evaluate the impact of a multifaceted laboratory reduction intervention on laboratory costs. DESIGN: A retrospective, controlled, interrupted time series (ITS) study. SETTING: University of Utah Health Care, a 500-bed academic medical center in Salt Lake City, Utah. POPULATION: All patients 18 years or older admitted to the hospital to a service other than obstetrics, rehabilitation, or psychiatry. INTERVENTION: Multifaceted quality-improvement initiative in a hospitalist service including education, process change, cost feedback, and financial incentive. MEASUREMENTS: Primary outcomes of lab cost per day and per visit. Secondary outcomes of number of basic metabolic panel (BMP), comprehensive metabolic panel (CMP), complete blood count (CBC), and prothrombin time/international normalized ratio tests per day; length of stay (LOS); and 30 day readmissions. RESULTS: A total of 6310 hospitalist patient visits (intervention group) were compared to 25,586 nonhospitalist visits (control group). Among the intervention group, the unadjusted mean cost per day was reduced from $138 before the intervention to $123 after the intervention (P < 0.001), and the unadjusted mean cost per visit decreased from $618 to $558 (P = 0.005). The ITS analysis showed significant reductions in cost per day, cost per visit, and the number of BMP, CMP, and CBC tests per day (P = 0.034, 0.02, <0.001, 0.004, and <0.001). LOS was unchanged and 30-day readmissions decreased in the intervention group. CONCLUSION: A multifaceted approach to laboratory reduction demonstrated a significant reduction in laboratory cost per day and per visit, as well as common tests per day at a major academic medical center. Journal of Hospital Medicine 2016;11:348-354. (c) 2016 Society of Hospital Medicine. PMID- 26843274 TI - Left main ostial agenesis and right coronary artery occlusion: the importance of the 'Vieussens' arterial ring'. PMID- 26843277 TI - Inflammatory cytokines in atherosclerosis: current therapeutic approaches. AB - The notion of atherosclerosis as a chronic inflammatory disease has intensified research on the role of cytokines and the way these molecules act and interact to initiate and sustain inflammation in the microenvironment of an atherosclerotic plaque. Cytokines are expressed by all types of cells involved in the pathogenesis of atherosclerosis, act on a variety of targets exerting multiple effects, and are largely responsible for the crosstalk among endothelial, smooth muscle cells, leucocytes, and other vascular residing cells. It is now understood that widely used drugs such as statins, aspirin, methotrexate, and colchicine act in an immunomodulatory way that may beneficially affect atherogenesis and/or cardiovascular disease progression. Moreover, advancement in pharmaceutical design has enabled the production of highly specific antibodies against key molecules involved in the perpetuation of the inflammatory cascade, raising hope for advances in the treatment of atherosclerosis. This review describes the actions and effects of these agents, their potential clinical significance, and future prospects. PMID- 26843275 TI - Highly sensitive troponin and coronary computed tomography angiography in the evaluation of suspected acute coronary syndrome in the emergency department. AB - The evaluation of patients presenting to the emergency department with suspected acute coronary syndrome (ACS) remains a clinical challenge. The traditional assessment includes clinical risk assessment based on cardiovascular risk factors with serial electrocardiograms and cardiac troponin measurements, often followed by advanced cardiac testing as inpatient or outpatient (i.e. stress testing, imaging). Despite this costly and lengthy work-up, there is a non-negligible rate of missed ACS with an increased risk of death. There is a clinical need for diagnostic strategies that will lead to rapid and reliable triage of patients with suspected ACS. We provide an overview of the evidence for the role of highly sensitive troponin (hsTn) in the rapid and efficient evaluation of suspected ACS. Results of recent research studies have led to the introduction of hsTn with rapid rule-in and rule-out protocols into the guidelines. Highly sensitive troponin increases the sensitivity for the detection of myocardial infarction and decreases time to diagnosis; however, it may decrease the specificity, especially when used as a dichotomous variable, rather than continuous variable as recommended by guidelines; this may increase clinician uncertainty. We summarize the evidence for the use of coronary computed tomography angiography (CTA) as the rapid diagnostic tool in this population when used with conventional troponin assays. Coronary CTA significantly decreases time to diagnosis and discharge in patients with suspected ACS, while being safe. However, it may lead to increase in invasive procedures and includes radiation exposure. Finally, we outline the opportunities for the combined use of hsTn and coronary CTA that may result in increased efficiency, decreased need for imaging, lower cost, and decreased radiation dose. PMID- 26843279 TI - Coronary microcirculatory pathophysiology: can we afford it to remain a black box? AB - Coronary microvascular networks play the key role in determining blood flow distribution in the heart. Matching local blood supply to tissue metabolic demand entails continuous adaptation of coronary vessels via regulation of smooth muscle tone and structural dilated vessel diameter. The importance of coronary microcirculation for relevant pathological conditions including angina in patients with normal or near-normal coronary angiograms [microvascular angina (MVA)] and heart failure with preserved ejection fraction (HFpEF) is increasingly recognized. For MVA, clinical studies have shown a prevalence of up to 40% in patients with suspected coronary artery disease and a relevant impact on adverse cardiovascular events including cardiac death, stroke, and heart failure. Despite a continuously increasing number of corresponding clinical studies, the knowledge on pathophysiological cause-effect relations involving coronary microcirculation is, however, still very limited. A number of pathophysiological hypotheses for MVA and HFpEF have been suggested but are not established to a degree, which would allow definition of nosological entities, stratification of affected patients, or development of effective therapeutic strategies. This may be related to a steep decline in experimental (animal) pathophysiological studies in this area during the last 15 years. Since technology to experimentally investigate microvascular pathophysiology in the beating heart is increasingly, in principle, available, a concerted effort to build 'coronary microcirculatory observatories' to close this gap and to accelerate clinical progress in this area is suggested. PMID- 26843281 TI - Catheter-based complete "Alfieri-Stich" via interventional annuloplasty and edge to-edge repair for degenerative mitral regurgitation. PMID- 26843280 TI - Current therapy and outcome of Eisenmenger syndrome: data of the German National Register for congenital heart defects. AB - AIMS: We aimed to assess the contemporary outcome of Eisenmenger syndrome (ES), delineate the use of disease targeting therapies (DTT) in these patients and to investigate the effect of treatment on outcome in the community. METHODS AND RESULTS: Patients with ES were systematically identified from the German National Register for Congenital Heart Defects. Data on underlying diagnosis, medical therapy, and survival were collected. The impact of DTT on survival was assessed using time-dependant Cox analysis. Overall, 153 ES patients were included (mean age 34.0 +/- 13.3 years, 46% females). Of these, 88 (57.5%) were treated with at least one DTT (76.1% Bosentan, 20.5% Sildenafil) while 17.6% were on dual DTT. In addition, 24.8% of patients received digoxin, 10.5% angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 17.6% beta-blockers. Moreover, 17.6% of patients were treated with oral anticoagulants, while 23.5% of patients received Aspirin. The survival rate at 1, 5, and 10 years of follow-up was only 92, 75, and 57% in the entire cohort, and was even worse in treatment naive ES patients (survival rate 86, 60, and 34% at 1, 5, and 10 years). Use of DTT was independently associated with a better survival (hazard ratio 0.42, P= 0.015). CONCLUSION: This study illustrates the alarmingly poor survival prospects of Eisenmenger patients by community-based data even in the current era with advanced DTT and in a country with a wealthy health system. Treatment naive ES patients had especially high mortality rates approaching 60-70% at 10 years of follow-up. Treatment with DTT was associated with better survival. PMID- 26843282 TI - Genome sequence and virulence factors of a group G Streptococcus dysgalactiae subsp. equisimilis strain with a new element carrying erm(B). AB - A Streptococcus dysgalactiae subsp. equisimilis (SDSE) strain WCHSDSE-1, which caused an outbreak of tonsillopharyngitis among healthcare workers in China, was subjected to genome sequencing and analysis. WCHSDSE-1 belongs to the Lancefield group G, emm type stG211.1 and sequence type 44. WCHSDSE-1 has virulence factors for adherence, impairing the recruitment of neutrophils to infection sites and toxins including streptolysins O and S and exotoxin G. WCHSDSE-1 has a 45.4-kb element resembling a conjugative transposon. This element is absent from other known SDSE genomes and contains the macrolide-resistant gene erm(B). Conjugative transfer of erm(B) was not successful in mating experiments, suggesting that the element might have lost its ability of conjugation. An almost identical element, which contains the tetracycline-resistant gene tet(M) instead of erm(B), is present on the genome of Filifactor alocis ATCC 35896. The boundaries and insertion sites of the two elements were identified and both were flanked by a 3 bp direct repeat, which is characteristic of transposition. In conclusion, the spectrum of virulence factors of WCHSDSE-1 is similar to other SDSE strains causing invasive diseases. WCHSDSE-1 possesses a new transposable element encoding macrolide resistance, which could pick up different resistance genes and could be transferred across species in oral microflora. PMID- 26843283 TI - Direct and sustained intracellular delivery of exogenous molecules using acoustic transfection with high frequency ultrasound. AB - Controlling cell functions for research and therapeutic purposes may open new strategies for the treatment of many diseases. An efficient and safe introduction of membrane impermeable molecules into target cells will provide versatile means to modulate cell fate. We introduce a new transfection technique that utilizes high frequency ultrasound without any contrast agents such as microbubbles, bringing a single-cell level targeting and size-dependent intracellular delivery of macromolecules. The transfection apparatus consists of an ultrasonic transducer with the center frequency of over 150 MHz and an epi-fluorescence microscope, entitled acoustic-transfection system. Acoustic pulses, emitted from an ultrasonic transducer, perturb the lipid bilayer of the cell membrane of a targeted single-cell to induce intracellular delivery of exogenous molecules. Simultaneous live cell imaging using HeLa cells to investigate the intracellular concentration of Ca(2+) and propidium iodide (PI) and the delivery of 3 kDa dextran labeled with Alexa 488 were demonstrated. Cytosolic delivery of 3 kDa dextran induced via acoustic-transfection was manifested by diffused fluorescence throughout whole cells. Short-term (6 hr) cell viability test and long-term (40 hr) cell tracking confirmed that the proposed approach has low cell cytotoxicity. PMID- 26843285 TI - The rise, fall, and possible resurrection of renal denervation. AB - Renal denervation has a chequered history. Dramatic reductions in blood pressure after denervation of the renal arteries were observed in early trials, but later trials in which denervation was tested against a sham procedure produced neutral results. Although a sound pathophysiological basis exists for interruption of the renal sympathetic nervous system as a treatment for hypertension, trial data to date are insufficient to support renal denervation as an established clinical therapy. In this Perspectives article, we summarize the currently available trial data, device development, and trials in progress, and provide recommendations for future trial design. PMID- 26843287 TI - Gene therapy: No improvement in outcomes with gene therapy for heart failure. PMID- 26843288 TI - Heart failure: Mechanisms of spinal cord neuromodulation for heart disease. PMID- 26843290 TI - Hypertension: Benefits of strict blood-pressure lowering in hypertension. PMID- 26843292 TI - Advancing China's health and medical science. PMID- 26843291 TI - Climate and health: preparing for Paris. PMID- 26843293 TI - We need to talk about Yemen. PMID- 26843289 TI - Ischaemic conditioning and reperfusion injury. AB - The 30-year anniversary of the discovery of 'ischaemic preconditioning' is in 2016. This endogenous phenomenon can paradoxically protect the heart from acute myocardial infarction by subjecting it to one or more brief cycles of ischaemia and reperfusion. Apart from complete reperfusion, this method is the most powerful intervention known for reducing infarct size. The concept of ischaemic preconditioning has evolved into 'ischaemic conditioning', a term that encompasses a number of related endogenous cardioprotective strategies, applied either directly to the heart (ischaemic preconditioning or postconditioning) or from afar, for example a limb (remote ischaemic preconditioning, perconditioning, or postconditioning). Investigations of signalling pathways underlying ischaemic conditioning have identified a number of therapeutic targets for pharmacological manipulation. Over the past 3 decades, a number of ischaemic and pharmacological cardioprotection strategies, discovered in experimental studies, have been examined in the clinical setting of acute myocardial infarction and CABG surgery. The results from many of the studies have been disappointing, and no effective cardioprotective therapy is currently used in clinical practice. Several large, multicentre, randomized, controlled clinical trials on cardioprotection have highlighted the challenges of translating ischaemic conditioning and pharmacological cardioprotection strategies into patient benefit. However, a number of cardioprotective therapies have shown promising results in reducing infarct size and improving clinical outcomes in patients with ischaemic heart disease. PMID- 26843294 TI - Providing incentives to share data early in health emergencies: the role of journal editors. PMID- 26843296 TI - Global Financing Facility: where will the funds come from? PMID- 26843297 TI - Dispute delays release of malaria money in Cambodia. PMID- 26843298 TI - Profile: NIMHD--NIH's institute for minority health. PMID- 26843301 TI - Words on the borders of the body. PMID- 26843302 TI - Suniti Solomon. PMID- 26843303 TI - Female genital fistula repair. PMID- 26843304 TI - Female genital fistula repair - Authors' reply. PMID- 26843305 TI - Central arteriovenous anastomosis and hypertension. PMID- 26843306 TI - Central arteriovenous anastomosis and hypertension - Authors' reply. PMID- 26843308 TI - Ureteric colic and clinical evidence - Authors' reply. PMID- 26843307 TI - Ureteric colic and clinical evidence. PMID- 26843309 TI - New guideline for idiopathic pulmonary fibrosis. PMID- 26843310 TI - The World Bank under the leadership of Jim Kim. PMID- 26843311 TI - Department of Error. PMID- 26843312 TI - Department of Error. PMID- 26843313 TI - Cutaneous nodules with positive autoantibodies: histoid leprosy. PMID- 26843314 TI - Cutaneous nodules with positive autoantibodies: diagnostic pitfalls. PMID- 26843315 TI - All or nothing? PMID- 26843316 TI - Waltzing around cofactors. AB - The metallocofactor involved in fixing nitrogen is not a rigid scaffold, as was previously thought. PMID- 26843317 TI - Normalised immune expression in remission of paediatric ITP. PMID- 26843318 TI - Heterologous Liposarcomatous Differentiation in Malignant Phyllodes Tumor is Histologically Similar but Immunohistochemically and Molecularly Distinct from Well-differentiated Liposarcoma of Soft Tissue. AB - Malignant phyllodes tumor (PT) infrequently displays heterologous differentiation, and when present is most often liposarcomatous. We identified five cases of malignant PT with regions identical to well-differentiated liposarcoma (WDLS) of soft tissue and evaluated them for MDM2 and CDK4 gene expression and amplification using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. Despite indistinguishable morphology all cases of malignant PT with WDLS-like liposarcomatous differentiation were negative for MDM2 and CDK4 IHC and FISH, supporting different underlying pathogenesis. PMID- 26843319 TI - Reduction of a diamidocarbene-supported borenium cation: isolation of a neutral boryl-substituted radical and a carbene-stabilized aminoborylene. AB - We have synthesized the first diamidocarbene (DAC)-supported borenium salt, [][OTf], which was found to readily undergo two sequential 1-electron reductions. The first reduction forms a thermally robust, crystalline boryl-substituted DAC centred radical () which has been fully characterized by XRD, EPR spectroscopy, and DFT analyses. The 1-electron reduction of resulted in the formation of a DAC supported aminoborylene, , which has been characterized computationally and by multinuclear NMR spectroscopy. PMID- 26843320 TI - Thermoreversible (Ionic-Liquid-Based) Aqueous Biphasic Systems. AB - The ability to induce reversible phase transitions between homogeneous solutions and biphasic liquid-liquid systems, at pre-defined and suitable operating temperatures, is of crucial relevance in the design of separation processes. Ionic-liquid-based aqueous biphasic systems (IL-based ABS) have demonstrated superior performance as alternative extraction platforms, and their thermoreversible behaviour is here disclosed by the use of protic ILs. The applicability of the temperature-induced phase switching is further demonstrated with the complete extraction of two value-added proteins, achieved in a single step. It is shown that these temperature-induced mono(bi)phasic systems are significantly more versatile than classical liquid-liquid systems which are constrained by their critical temperatures. IL-based ABS allow to work in a wide range of temperatures and compositions which can be tailored to fit the requirements of a given separation process. PMID- 26843322 TI - Mechanics at the glass-to-gel transition of thermoresponsive microgel suspensions. AB - We study the rheology of systems of thermoresponsive microgels which can transition between a repulsive glass and an attractive gel state. We find marked differences between these two colloidal solids, within the same experimental system, due to the different origins for their dynamic arrest. While the rigidity of the repulsive systems depends solely on particle volume fraction, we find that the change in linear elasticity upon introducing attractive bonds in the system scales linearly with the adhesive bond strength which can be tuned with the temperature in our experiments. And while the glasses yield reversibly and with a rate-dependent energy dissipation, bond-reorganisation in the gels is suppressed so that their rupture is irreversible and accompanied by a high, but rate independent, dissipation. These results highlight how colloids with responsive interactions can be employed to shed new light onto solid-solid transitions. PMID- 26843321 TI - Role of transcription factor-mediated nucleosome disassembly in PHO5 gene expression. AB - Studying nucleosome dynamics in promoter regions is crucial for understanding gene regulation. Nucleosomes regulate gene expression by sterically occluding transcription factors (TFs) and other non-histone proteins accessing genomic DNA. How the binding competition between nucleosomes and TFs leads to transcriptionally compatible promoter states is an open question. Here, we present a computational study of the nucleosome dynamics and organization in the promoter region of PHO5 gene in Saccharomyces cerevisiae. Introducing a model for nucleosome kinetics that takes into account ATP-dependent remodeling activity, DNA sequence effects, and kinetics of TFs (Pho4p), we compute the probability of obtaining different "promoter states" having different nucleosome configurations. Comparing our results with experimental data, we argue that the presence of local remodeling activity (LRA) as opposed to basal remodeling activity (BRA) is crucial in determining transcriptionally active promoter states. By modulating the LRA and Pho4p binding rate, we obtain different mRNA distributions-Poisson, bimodal, and long-tail. Through this work we explain many features of the PHO5 promoter such as sequence-dependent TF accessibility and the role of correlated dynamics between nucleosomes and TFs in opening/coverage of the TATA box. We also obtain possible ranges for TF binding rates and the magnitude of LRA. PMID- 26843323 TI - Colorectal cancer surgery for obese patients: Financial and clinical outcomes of a Dutch population-based registry. AB - BACKGROUND AND OBJECTIVES: The objective of this study was to explore the association among adverse events, body mass index (BMI), and hospital costs after colorectal cancer surgery in a country with an intermediate BMI distribution. METHODS: All colorectal cancer procedures in 29 Dutch hospitals listed in a 2010 2012 population-based database and with a BMI > 18.5 were included (n = 8687). Hospital costs were measured uniformly and based on time-driven activity-based costing. The BMI classification of the World Health Organization was used. RESULTS: Patients in obesity classes 1 (23.6% [after risk-adjustment OR 1.245, CI 1.064-1.479, P = 0.007]) and >=2 (28.1% [after risk-adjustment OR 1.816, CI 1.382 2.388, P < 0.001]) were associated with more severe complications and higher hospital costs (?14,294, +9.6%, after risk-adjustment +7.9%, P < 0.001; and ?15,913 +22.0%, after risk-adjustment +21.2%, P < 0.001, respectively) than normal weight patients (20.8% and ?13,040, respectively). Pre-obese patients had significantly lower mortality rates (2.7%, after risk-adjustment, OR 0.756, CI 0.577-0.991, P = 0.042) than normal-weight patients (3.9%). CONCLUSIONS: Obese surgical colorectal cancer patients in a country with an intermediate BMI distribution are associated with a significant increase in hospital costs because these patients suffer from more severe complications. This is the first study to provide evidence for the "obesity-paradox" for mortality in colorectal cancer surgery. J. Surg. Oncol. 2016;113:489-495. (c) 2016 Wiley Periodicals, Inc. PMID- 26843324 TI - Cutting Edge: Expression of IRF8 in Gastric Epithelial Cells Confers Protective Innate Immunity against Helicobacter pylori Infection. AB - IFN regulatory factor 8 (IRF8) is expressed in many types of blood cells and plays critical roles in cellular differentiation and function. However, the role of IRF8 in nonhematopoietic systems remains poorly understood. In this study, we provide evidence that IRF8 is a transcriptional modulator of the gastric mucosa necessary for limiting Helicobacter pylori colonization. H. pylori infection significantly upregulated expression of IRF8, which, in turn, promoted IFN-gamma expression by gastric epithelial cells. Mice deficient in IRF8 exhibited increased H. pylori colonization and aborted induction of mucosal IFN-gamma. Genome-wide analyses of IFN-gamma-treated gastric epithelial cells by chromatin immunoprecipitation sequencing and RNA sequencing led to the identification of IRF8 target genes, with many belonging to the IFN-regulated gene family that was observed previously in immune cells. Our results identify the IRF8-IFN-gamma circuit as a novel gastric innate immune mechanism in the host defense against infection with H. pylori. PMID- 26843325 TI - Survival of Igalpha-Deficient Mature B Cells Requires BAFF-R Function. AB - Expression of a functional BCR is essential for the development of mature B cells and has been invoked in the control of their maintenance. To test this maintenance function in a new experimental setting, we used the tamoxifen inducible mb1-CreER(T2) mouse strain to delete or truncate either the mb-1 gene encoding the BCR signaling subunit Igalpha or the VDJ segment of the IgH (H chain [HC]). In this system, Cre-mediated deletion of the mb-1 gene is accompanied by expression of a GFP reporter. We found that, although the Igalpha-deficient mature B cells survive for >20 d in vivo, the HC-deficient or Igalpha tail truncated B cell population is short-lived, with the HC-deficient cells displaying signs of an unfolded protein response. We also show that Igalpha deficient B cells still respond to the prosurvival factor BAFF in culture and require BAFF-R signaling for their in vivo maintenance. These results suggest that, under certain conditions, the loss of the BCR can be tolerated by mature B cells for some time, whereas HC-deficient B cells, potentially generated by aberrant somatic mutations in the germinal center, are rapidly eliminated. PMID- 26843326 TI - Retinoic Acid Receptor gamma Regulates B and T Lymphopoiesis via Nestin Expressing Cells in the Bone Marrow and Thymic Microenvironments. AB - Vitamin A has essential but largely unexplained roles in regulating lymphopoiesis. We have previously shown that retinoic acid receptor (RAR) gamma deficient mice have hematopoietic defects, some phenotypes of which were microenvironment induced. Bone marrow (BM) microenvironment cells identified by either their expression of nestin (Nes) or osterix (Osx) have previously been shown to have roles in regulating lymphopoiesis. We therefore conditionally deleted Rargamma in Nes- or Osx-expressing microenvironment cells. Osx cell specific deletion of Rargamma had no impact on hematopoiesis. In contrast, deletion of Rargamma in Nes-expressing cells resulted in reductions in peripheral blood B cells and CD4(+) T cells, accompanied by reductions of immature PreB cells in BM. The mice lacking Rargamma in Nes-expressing cells also had smaller thymi, with reductions in double-negative 4 T cell precursors, accompanied by reduced numbers of both TCRbeta(low) immature single-positive CD8(+) cells and double-positive T cells. In the thymus, Nes expression was restricted to thymic stromal cells that expressed cerebellar degeneration-related Ag 1 and lacked expression of epithelial cell adhesion molecule. These cells expressed platelet derived growth factor alpha and high transcript levels of Rars, Cxcl12, and stem cell factor (Scf). Short-term treatment of mice with all-trans retinoic acid resulted in increased PreB lymphopoiesis in BM and an increase in thymic double negative 4 T cells, inverse to that observed upon Nes cell-specific deletion of Rargamma. Collectively, these studies show that RARgamma is a regulator of B and T lymphopoiesis via Nes-expressing cells in the BM and thymic microenvironments, respectively. PMID- 26843327 TI - Yin Yang 1 Promotes Thymocyte Survival by Downregulating p53. AB - Yin Yang 1 (YY1) is a zinc finger protein that functions as a transcriptional activator or repressor and participates in multiple biological processes, including development and tumorigenesis. To investigate the role of YY1 in developing T cells, we used mouse models that depleted YY1 at two distinct stages of thymocyte development. When YY1 was depleted in CD4(-)CD8(-) double-negative thymocytes, development to the CD4(+)CD8(+) double-positive stage was impaired, due to increased apoptosis that prevented expansion of post-beta-selection thymocytes. When YY1 was depleted in double-positive thymocytes, they underwent increased cell-autonomous apoptosis in vitro and displayed a shorter lifespan in vivo, as judged by their ability to undergo secondary Valpha-to-Jalpha recombination. Mechanistically, we found that the increased apoptosis in YY1 deficient thymocytes was attributed to overexpression of p53, because concurrent loss of p53 completely rescued the developmental defects of YY1-deficient thymocytes. These results indicated that YY1 functions as a critical regulator of thymocyte survival and that it does so by suppressing the expression of p53. PMID- 26843328 TI - Characterization and Application of a Unique Panel of Monoclonal Antibodies Generated against Etanercept. AB - The clinical response in ankylosing spondylitis (AS) patients treated with biologic agents can be influenced by pharmacokinetic variability among and within these patients. Therapeutic drug monitoring is seen as a valuable tool to improve patient care. The aim of this study was to generate a panel of mAbs toward etanercept (ETN) and to determine ETN and anti-ETN concentrations in AS patients. mAbs against ETN (MA-ETN) were generated using hybridoma technology. For quantification of ETN concentrations, a mAb-based TNF-coated ELISA and a mAb/mAb based sandwich-type ELISA were developed. For evaluation of the anti-ETN Ab response, a bridging ELISA, as well as a functional cell-based assay, were constructed. Disease activity of the AS patients was measured with the AS Disease Activity Score (ASDAS). Active disease was defined as ASDAS >= 2.1. A total of 59 of 76 generated mAbs were ETN specific and were characterized further. Fifty-one mAbs revealed inhibitory properties in a cell-based assay. Analysis of serum concentrations of 21 ETN-treated AS patients with the TNF/MA-ETN68C5-HRP ELISA and the MA-ETN63C8/MA-ETN61C1-HRP ELISA revealed a good Pearson's r (+0.974) but a poor intraclass correlation coefficient (+0.528) as the result of underestimation of the values in the former ELISA. At 24 wk, ETN concentrations were similar in patients with ASDAS < 2.1 and >= 2.1. Anti-ETN Abs were not detected in any of the patient samples tested. In conclusion, highly sensitive mAb-based immunoassays were developed for quantification of ETN and anti-ETN concentrations. The impact of these methods needs to be evaluated further in clinical practice. PMID- 26843329 TI - GAPDH Binding to TNF-alpha mRNA Contributes to Posttranscriptional Repression in Monocytes: A Novel Mechanism of Communication between Inflammation and Metabolism. AB - Expression of the inflammatory cytokine TNF is tightly controlled. During endotoxin tolerance, transcription of TNF mRNA is repressed, although not entirely eliminated. Production of TNF cytokine, however, is further controlled by posttranscriptional regulation. In this study, we detail a mechanism of posttranscriptional repression of TNF mRNA by GAPDH binding to the TNF 3' untranslated region. Using RNA immunoprecipitation, we demonstrate that GAPDH-TNF mRNA binding increases when THP-1 monocytes are in a low glycolysis state, and that this binding can be reversed by knocking down GAPDH expression or by increasing glycolysis. We show that reducing glycolysis decreases TNF mRNA association with polysomes. We demonstrate that GAPDH-TNF mRNA binding results in posttranscriptional repression of TNF and that the TNF mRNA 3' untranslated region is sufficient for repression. Finally, after exploring this model in THP-1 cells, we demonstrate this mechanism affects TNF expression in primary human monocytes and macrophages. We conclude that GAPDH-TNF mRNA binding regulates expression of TNF based on cellular metabolic state. We think this mechanism has potentially significant implications for treatment of various immunometabolic conditions, including immune paralysis during septic shock. PMID- 26843330 TI - Inducible Major Vault Protein Plays a Pivotal Role in Double-Stranded RNA- or Virus-Induced Proinflammatory Response. AB - Pathogen invasion triggers robust antiviral cytokine production via different transcription factor signaling pathways. We have previously demonstrated that major vault protein (MVP) induces type I IFN production during viral infection; however, little is known about the role of MVP in proinflammatory responses. In this study, we found in vitro that expression of MVP, IL-6, and IL-8 was inducible upon dsRNA stimulation or viral infection. Moreover, MVP was essential for the induction of IL-6 and IL-8, as impaired expression of IL-6 and IL-8 in MVP-deficient human PBMCs, human lung epithelial cells (A549), and THP-1 monocytes, as well as in murine splenocytes, peritoneal macrophages, and PBMCs from MVP-knockout (MVP(-/-)) mice, was observed. Upon investigation of the underlying mechanisms, we demonstrated that MVP acted in synergy with AP-1 (c Fos) and CCAAT/enhancer binding protein (C/EBP)beta-liver-enriched transcriptional activating protein to activate the IL6 and IL8 promoters. Introduction of mutations into the AP-1 and C/EBPbeta binding sites on the IL6 and IL8 promoters resulted in the loss of synergistic activation with MVP. Furthermore, we found that MVP interacted with both c-Fos and C/EBPbeta. The interactions promoted nuclear translocation and recruitment of these transcription factors to IL6 and IL8 promoter regions. In the MVP(-/-) mouse model, significantly decreased expression of early antiviral cytokines resulted in higher viral titer in the lung, higher mortality, and heavier lung damage after infection with lethal influenza A virus. Taken together, our findings help to delineate a novel role of MVP in host proinflammatory response. PMID- 26843332 TI - Obstructive sleep apnea is associated with low GABA and high glutamate in the insular cortex. AB - The insular cortex is injured in obstructive sleep apnea (OSA) and responds inappropriately to autonomic challenges, suggesting neural reorganization. The objective of this study was to assess whether the neural changes might result from gamma-aminobutyric acid (GABA) and glutamate alterations. We studied 14 OSA patients [mean age +/- standard deviation (SD): 47.5 +/- 10.5 years; nine male; apnea-hypopnea index (AHI): 29.5 +/- 15.6 events h(-1) ] and 22 healthy participants (47.5 +/- 10.1 years; 11 male), using magnetic resonance spectroscopy to detect GABA and glutamate levels in insular cortices. We localized the cortices with anatomical scans, and measured neurochemical levels from anterior to mid-regions. Left and right anterior insular cortices showed lower GABA and higher glutamate in OSA versus healthy subjects [GABA left: OSA n = 6: 0.36 +/- 0.10 (mean +/- SD), healthy n = 5: 0.62 +/- 0.18; P < 0.05), right: OSA n = 11: 0.27 +/- 0.09, healthy n = 14: 0.45 +/- 0.16; P < 0.05; glutamate left: OSA n = 6: 1.61 +/- 0.32, healthy n = 8: 0.94 +/- 0.34; P < 0.05, right: OSA n = 14: 1.26 +/- 0.28, healthy n = 19: 1.02 +/- 0.28; P < 0.05]. GABA and glutamate levels were correlated only within the healthy group in the left insula (r: -0.9, P < 0.05). The altered anterior insular levels of GABA and glutamate may modify integration and projections to autonomic areas, contributing to the impaired cardiovascular regulation in OSA. PMID- 26843333 TI - Spatzle-Processing Enzyme-independent Activation of the Toll Pathway in Drosophila Innate Immunity. AB - The Toll pathway regulates innate immunity in insects and vertebrates. The Drosophila Toll receptor is activated by a processed form of a ligand, Spatzle. Spatzle-processing enzyme (SPE) is the only enzyme identified to date that functions in converting Spatzle to an active form during the immune response. In the present study, Toll activation induced by immune challenge was almost suppressed in spatzle mutant larvae and adults, whereas it was present in SPE mutant larvae challenged with Micrococcus luteus and adults challenged with Bacillus subtilis. Our data suggest that an unidentified protease besides SPE processes Spatzle under conditions of microbial challenge. PMID- 26843331 TI - Resolvin D1 Dampens Pulmonary Inflammation and Promotes Clearance of Nontypeable Haemophilus influenzae. AB - Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative, opportunistic pathogen that frequently causes ear infections, bronchitis, pneumonia, and exacerbations in patients with underlying inflammatory diseases, such as chronic obstructive pulmonary disease. In mice, NTHi is rapidly cleared, but a strong inflammatory response persists, underscoring the concept that NTHi induces dysregulation of normal inflammatory responses and causes a failure to resolve. Lipid-derived specialized proresolving mediators (SPMs) play a critical role in the active resolution of inflammation by both suppressing proinflammatory actions and promoting resolution pathways. Importantly, SPMs lack the immunosuppressive properties of classical anti-inflammatory therapies. On the basis of these characteristics, we hypothesized that aspirin-triggered resolvin D1 (AT-RvD1) would dampen NTHi-induced inflammation while still enhancing bacterial clearance. C57BL/6 mice were treated with AT-RvD1 and infected with live NTHi. AT-RvD1 treated mice had lower total cell counts and neutrophils in bronchoalveolar lavage fluid, and had earlier influx of macrophages. In addition, AT-RvD1-treated mice showed changes in temporal regulation of inflammatory cytokines and enzymes, with decreased KC at 6 h and decreased IL-6, TNF-alpha, and cyclooxygenase-2 expression at 24 h post infection. Despite reduced inflammation, AT-RvD1-treated mice had reduced NTHi bacterial load, mediated by enhanced clearance by macrophages and a skewing toward an M2 phenotype. Finally, AT-RvD1 protected NTHi infected mice from weight loss, hypothermia, hypoxemia, and respiratory compromise. This research highlights the beneficial role of SPMs in pulmonary bacterial infections and provides the groundwork for further investigation into SPMs as alternatives to immunosuppressive therapies like steroids. PMID- 26843335 TI - Editorial: can MRI enterography be an efficient tool for patient selection in clinical trials? PMID- 26843334 TI - Transplanted neurons integrate into adult retinas and respond to light. AB - Retinal ganglion cells (RGCs) degenerate in diseases like glaucoma and are not replaced in adult mammals. Here we investigate whether transplanted RGCs can integrate into the mature retina. We have transplanted GFP-labelled RGCs into uninjured rat retinas in vivo by intravitreal injection. Transplanted RGCs acquire the general morphology of endogenous RGCs, with axons orienting towards the optic nerve head of the host retina and dendrites growing into the inner plexiform layer. Preliminary data show in some cases GFP(+) axons extending within the host optic nerves and optic tract, reaching usual synaptic targets in the brain, including the lateral geniculate nucleus and superior colliculus. Electrophysiological recordings from transplanted RGCs demonstrate the cells' electrical excitability and light responses similar to host ON, ON-OFF and OFF RGCs, although less rapid and with greater adaptation. These data present a promising approach to develop cell replacement strategies in diseased retinas with degenerating RGCs. PMID- 26843336 TI - Editorial: serotonin and irritable bowel syndrome--reconciling pharmacological effects with basic biology. PMID- 26843337 TI - Editorial: serotonin and irritable bowel syndrome--reconciling pharmacological effects with basic biology; authors' reply. PMID- 26843338 TI - Editorial: proton pump inhibitors, Helicobacter pylori and gastric cancer--the need for long-term follow-up. PMID- 26843339 TI - Editorial: fenofibrate as second-line therapy in high risk PBC--more answers or more questions? PMID- 26843340 TI - Editorial: fenofibrate as second-line therapy in high risk PBC--more answers or more questions? Authors' reply. PMID- 26843341 TI - Editorial: improved understanding of the epidemiology of primary biliary cirrhosis in South Korea. PMID- 26843342 TI - Editorial: how to interpret risks and prediction of complications in Crohn's disease--can our patients interpret them? PMID- 26843343 TI - Editorial: how to interpret risks and prediction of complications in Crohn's disease--can our patients interpret them? Authors' reply. PMID- 26843344 TI - Letter: nucleos(t)ide analogues are good, but not sufficient for hepatitis B virus clearance. PMID- 26843345 TI - Letter: nucleos(t)ide analogues are good, but not sufficient for hepatitis B virus clearance--author's reply. PMID- 26843346 TI - Letter: gluten challenge in the era of noncoeliac gluten sensitivity--a change in clinical practice? Author's reply. PMID- 26843347 TI - Letter: gluten challenge in the era of noncoeliac gluten sensitivity--a change in clinical practice? PMID- 26843348 TI - Letter: effectiveness of golimumab to induce remission in outpatient ulcerative colitis in Italy. PMID- 26843349 TI - Letter: abnormal bone densitometry in patients with coeliac disease -beyond malabsorption and sunlight exposure. PMID- 26843350 TI - Letter: the liver to abdominal area ratio--a novel imaging score for prognostication in cirrhosis. PMID- 26843351 TI - Letter: the liver to abdominal area ratio--a novel imaging score for prognostication in cirrhosis--authors' reply. PMID- 26843352 TI - The greatly misunderstood erythropoietin resistance index and the case for a new responsiveness measure. AB - Introduction The optimal use of erythropoiesis stimulating agents (ESAs) to treat anemia in end stage renal disease remains controversial due to reported associations with adverse events. In analyzing these associations, studies often utilize ESA resistance indices (ERIs), to characterize a patient's response to ESA. In this study, we examine whether ERI is an adequate measure of ESA resistance. Methods We used retrospective data from a nonconcurrent cohort study of incident hemodialysis patients in the United States (n = 9386). ERI is defined as average weekly erythropoietin (EPO) dose per kg body weight (wt) per average hemoglobin (Hgb), over a 3-month period (ERI = (EPO/wt)/Hgb). Linear regression was used to demonstrate the relationship between ERI and weight-adjusted EPO. The coefficient of variation was used to compare the variability of Hgb with that of weight-adjusted EPO to explain this relationship. This analysis was done for each quarter during the first year of dialysis. Findings ERI is strongly linearly related with weight-adjusted EPO dose in each of the four quarters by the equation ERI = 0.0899*(EPO/wt) (range of R(2) = 0.97-0.98) and weakly linearly related to 1/Hgb (range of R(2) = 0.06-0.16). These correlations hold independent of age, sex, hgb level, ERI level, and epo-naive stratifications. Discussion ERI is strongly linearly related to weight-adjusted (and nonweight adjusted) EPO dose by a "universal," not patient-specific formula, and thus is a surrogate of EPO dose. Therefore, associations between ERI and clinical outcomes are associations between a confounded EPO dose and those outcomes. PMID- 26843353 TI - Impact of coexisting aneurysms on open revascularization for aortoiliac occlusive disease. AB - OBJECTIVE: National data evaluating outcomes for occlusive abdominal aortic reconstructions are well described. The relative effect of operative indication as well as the presence of concomitant abdominal aortic aneurysm (AAA) on in hospital mortality is not well defined. METHODS: The Nationwide Inpatient Sample was queried to identify patients who underwent open aortic surgery (2003-2010). Indication for surgery was classified by International Classification of Diseases, Ninth Revision diagnostic codes to identify isolated occlusive indications as well as combined occlusive disease and AAA. Primary outcome was in hospital mortality. Secondary outcomes were complications and discharge disposition. RESULTS: Overall, 56,374 underwent aortic reconstruction, 48,591 for occlusive disease (86.2%) and 7783 for combined occlusive disease with AAA (13.8%). Intermittent claudication was the most common indication for intervention (60.9%), whereas 39.7% underwent intervention for critical limb ischemia (22.2% rest pain, 17.6% gangrene). Patients with intermittent claudication had more concomitant AAAs (17.3%) than did patients with critical limb ischemia (8.4%). The baseline characteristics for those with occlusive disease and combined occlusive with AAA disease were similar in terms of obesity (4.8% vs 4.2%; P = .27) and congestive heart failure (6.6% vs 6.3%; P = .65) but differed by age (62.2 years vs 68.4 years; P < .0001) and hypertension (65.4% vs 69.1%; P = .005). Patients with combined occlusive and AAA disease had higher mortality than those with occlusive disease alone (3.9% vs 2.7%; P = .01). On multivariable regression, factors associated with in-hospital mortality included gangrene with AAA compared with gangrene alone (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.6-4.7; P < .0002), age >65 years age (OR, 3.1; 95% CI, 2.4-4.1; P < .0001), renal failure (OR, 2.7; 95% CI, 1.9-3.8; P < .0001), and concurrent lower extremity revascularization (OR, 1.3; 95% CI, 1.1-1.7; P < .02). CONCLUSIONS: Intermittent claudication or critical limb ischemia with concomitant AAA carries a higher mortality than intermittent claudication or critical limb ischemia alone, especially in older patients with gangrene requiring revascularization and renal insufficiency. Preoperative risk stratification strategies should focus on the indication for surgery as well as the presence of concomitant AAA. PMID- 26843354 TI - Assessment of open operative vascular surgical experience among general surgery residents. AB - BACKGROUND: General surgeons have traditionally performed open vascular operations. However, endovascular interventions, vascular residencies, and work hour limitations may have had an impact on open vascular surgery training among general surgery residents. We evaluated the temporal trend of open vascular operations performed by general surgery residents to assess any changes that have occurred. METHODS: The Accreditation Council for Graduate Medical Education's database was used to evaluate graduating general surgery residents' cases from 1999 to 2013. Mean and median case volumes were analyzed for carotid endarterectomy, open aortoiliac aneurysm repair, and lower extremity bypass. Significance of temporal trends were identified using the R(2) test. RESULTS: The average number of carotid endarterectomies performed by general surgery residents decreased from 23.1 +/- 14 (11.6 +/- 9 chief, 11.4 + 10 junior) cases per resident in 1999 to 10.7 +/- 9 (3.4 +/- 5 chief, 7.3 +/- 6 junior) in 2012 (R(2) = 0.98). Similarly, elective open aortoiliac aneurysm repairs decreased from 7.4 +/- 5 (4 +/- 4 chief, 3.4 +/- 4 junior) in 1999 to 1.3 +/- 2 (0.4 +/- 1 chief, 0.8 +/- 1 junior) in 2012 (R(2) = 0.98). The number of lower extremity bypasses decreased from 21 +/- 12 (9.5 +/- 7 chief, 11.8 +/- 9 junior) in 1999 to 7.6 +/- 2.6 (2.4 +/- 1.3 chief, 5.2 + 1.8 junior) in 2012 (R(2) = 0.94). Infrapopliteal bypasses decreased from 8.1 +/- 3.8 (3.5 +/- 2.2 chief, 4.5 +/- 2.9 junior) in 2001 to 3 +/- 2.2 (1 +/- 1.6 chief, 2 +/- 1.6 junior) in 2012 (R(2) = 0.94). CONCLUSIONS: General surgery resident exposure to open vascular surgery has significantly decreased. Current and future graduates may not have adequate exposure to open vascular operations to be safely credentialed to perform these procedures in future practice without advanced vascular surgical training. PMID- 26843356 TI - Protective effects of rice dreg protein hydrolysates against hydrogen peroxide induced oxidative stress in HepG-2 cells. AB - In this paper, the effects of rice dreg protein hydrolysates (RDPHs) obtained by various proteases on hydrogen peroxide-induced oxidative stress in HepG-2 cells were investigated. Cell cytotoxicity was evaluated through the aspects of cell viability, ROS level, antioxidant enzyme activity, and production of malondialdehyde (MDA). Cell apoptosis was assessed by flow cytometry. Molecular weight distribution was analyzed by gel permeation chromatography, and amino acid composition was measured using an automatic amino acid analyzer. The survival of cells and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were significantly increased through the pre-incubation of HepG-2 cells with RDPHs before H2O2 exposure. Additionally, these pretreatments also resulted in a reduction in ROS and MDA levels. As a result, apoptosis and loss of mitochondrial membrane potential of the HepG-2 cells were alleviated. Furthermore, the protective effects of protein hydrolysates obtained by various proteases were noticeably distinct, in which RDPHs prepared by alkaline protease showed higher antioxidant activities. The difference in the protective effects might be attributed to the specific peptide or amino acid composition. Therefore, enzymatic hydrolysis with different enzymes studied here could attenuate H2O2 induced cell damage, and the type of protease greatly influenced the anti oxidative activity. Particularly, optimum use of Alcalase could produce peptides with higher antioxidant activity. PMID- 26843355 TI - In-hospital outcomes in patients with critical limb ischemia and end-stage renal disease after revascularization. AB - OBJECTIVE: Analysis of in-hospital outcomes in patients treated for critical limb ischemia (CLI) and end-stage renal disease (ESRD) compared to CLI patients with normal renal function. METHODS: A subgroup analysis of the German CRITISCH registry, a prospective multicenter registry, assessing the first-line treatment strategies in CLI patients in 27 vascular centers in Germany was performed. The study cohort was divided into ESRD patients (n = 102) and patients with normal renal function (n = 674; glomerular filtration rate >60/mL/min/1.73 m(2)). The following first-line treatment strategies were assessed: endovascular therapy (EVT), bypass surgery, patch plasty, and no vascular intervention (conservative treatment, primary amputation). Uni- and multivariate analyses were performed to identify differences between groups as to six end points: amputation or death (composite end point), amputation, death, hemodynamic failure, major adverse cardiac and cerebrovascular events, and reintervention. RESULTS: Differences between the ESRD and non-ESRD group were found regarding the applied first-line therapy (P = .016): The first-line treatment strategies in ESRD patients were EVT in 64% (n = 65), bypass surgery in 13% (n = 13), patch plasty in 11% (n = 11), and no vascular intervention in 13% (n = 13). In non-ESRD patients, EVT was applied in 48% (n = 326), bypass surgery in 27% (n = 185), patch plasty in 13% (n = 86), and no vascular intervention in 11% (n = 77). For ESRD patients, a noticeably increased risk of the composite end point (odds ratio [OR], 2.62; 95% confidence interval [CI], 1.19-5.79; P = .017), amputation (OR, 3.14; 95% CI, 1.35-7.31; P = .008), and hemodynamic failure (OR, 2.19; 95% CI, 1.19-4.04; P = .012) was observed. CONCLUSIONS: CLI patients on dialysis represent a challenging cohort prone to in-hospital death, amputation, and hemodynamic failure. Two thirds of these high-risk patients are treated with EVT. Present data suggest that this modality is generally considered as the most favorable treatment option in this patient subgroup. PMID- 26843357 TI - Prenatal and early life exposure to traffic pollution and cardiometabolic health in childhood. AB - BACKGROUND: Prenatal exposure to traffic pollution has been associated with faster infant weight gain, but implications for cardiometabolic health in later childhood are unknown. METHODS: Among 1418 children in Project Viva, a Boston area pre-birth cohort, we assessed anthropometric and biochemical parameters of cardiometabolic health in early (median age 3.3 years) and mid- (median age 7.7 years) childhood. We used spatiotemporal models to estimate prenatal and early life residential PM2.5 and black carbon exposure as well as traffic density and roadway proximity. We performed linear regression analyses adjusted for sociodemographics. RESULTS: Children whose mothers lived close to a major roadway at the time of delivery had higher markers of adverse cardiometabolic risk in early and mid-childhood. For example, total fat mass was 2.1 kg (95%CI: 0.8, 3.5) higher in mid-childhood for children of mothers who lived <50 m vs. >=200 m from a major roadway. Black carbon exposure and traffic density were generally not associated with cardiometabolic parameters, and PM2.5 exposure during the year prior was paradoxically associated with improved cardiometabolic profile. CONCLUSIONS: Infants whose mothers lived close to a major roadway at the time of delivery may be at later risk for adverse cardiometabolic health. PMID- 26843358 TI - Sensory gating, inhibition control and gamma oscillations in the human somatosensory cortex. AB - Inhibiting the responses to irrelevant stimuli is an essential component of human cognitive function. Pre-attentive auditory sensory gating (SG), an attenuated neural activation to the second identical stimulus, has been found to be related to the performance of higher-hierarchical brain function. However, it remains unclear whether other cortical regions, such as somatosensory cortex, also possess similar characteristics, or if such a relationship is modality-specific. This study used magnetoencephalography to record neuromagnetic responses to paired-pulse electrical stimulation to median nerve in 22 healthy participants. Somatosensory SG ratio and cortical brain oscillations were obtained and compared with the behavioral performance of inhibition control, as evaluated by somatosensory and auditory Go-Nogo tasks. The results showed that somatosensory P35m SG ratio correlated with behavioral performance of inhibition control. Such relationship was also established in relation to the auditory Go-Nogo task. Finally, a higher frequency value of evoked gamma oscillations was found to relate to a better somatosensory SG ability. In conclusion, our data provided an empirical link between automatic cortical inhibition and behavioral performance of attentive inhibition control. This study invites further research on the relationships among gamma oscillations, neurophysiological indices, and behavioral performance in clinical populations in terms of SG or cortical inhibition. PMID- 26843359 TI - Transcriptional Regulation of Atp-Dependent Chromatin Remodeling Factors: Smarcal1 and Brg1 Mutually Co-Regulate Each Other. AB - The ATP-dependent chromatin remodeling factors regulate gene expression. However, it is not known whether these factors regulate each other. Given the ability of these factors to regulate the accessibility of DNA to transcription factors, we postulate that one ATP-dependent chromatin remodeling factor should be able to regulate the transcription of another ATP-dependent chromatin remodeling factor. In this paper, we show that BRG1 and SMARCAL1, both members of the ATP-dependent chromatin remodeling protein family, regulate each other. BRG1 binds to the SMARCAL1 promoter, while SMARCAL1 binds to the brg1 promoter. During DNA damage, the occupancy of SMARCAL1 on the brg1 promoter increases coinciding with an increase in BRG1 occupancy on the SMARCAL1 promoter, leading to increased brg1 and SMARCAL1 transcripts respectively. This is the first report of two ATP dependent chromatin remodeling factors regulating each other. PMID- 26843360 TI - Perforin expression in eyelid sebaceous carcinomas: a useful and specific immunomarker for the differential diagnosis of eyelid carcinomas. AB - PURPOSE: Eyelid sebaceous carcinoma (SC) remains a common diagnostic pitfall for both the clinician and histopathologist. The aim of this study was to describe perforin as a new marker in the immunohistochemistry panel for SC. METHODS: A total of 29 cases were retrieved from the Pathology archives, including 11 sebaceous neoplasms (nine SC; two sebaceomas), 10 squamous cell carcinomas (SCC) and eight basal cell carcinomas (BCC). These were stained using the monoclonal antibody for perforin, epithelial membrane antigen (EMA), Ber-EP4 and adipophilin (ADP). Sensitivity and specificity of perforin as an immunohistologic marker for sebaceous tumours were compared to EMA, ADP and Ber-EP4. RESULTS: Perforin stained strongly 9/11 (81%) of the sebaceous neoplasms (SN), 7/9 SC and 2/2 of sebaceomas (2/2), similar to ADP. Epithelial membrane antigen (EMA) stained 8/9 SC and was negative (1/2) or only very weakly expressed (1/2) in sebaceomas. The specificity of perforin in identifying SN versus SCC and BCC was 100% (95% CI 69 100), while EMA specificity in identifying SN varied according the comparison group (SCC: 50%, 95% CI 18-81, 100% (95% CI 63-100). Perforin better highlighted the intraepithelial spread of SC than EMA. Ber-EP4 was strongly expressed in six of nine SC, but was consistently negative in sebaceomas. CONCLUSIONS: The expression pattern of perforin in sebaceous neoplasms enables us to recommend the use of perforin as a new immunohistochemical marker for sebaceous neoplasms. PMID- 26843361 TI - Return to work after stroke: The KOSCO Study. AB - OBJECTIVE: To investigate the return to work status of patients with first-ever stroke with functional independence 6 months post-stroke. DESIGN: Prospective cohort study. PARTICIPANTS: Nine hundred and thirty-three patients with functional independence at 6 months after stroke onset. METHODS: A complete post enumeration survey was performed through a review of the medical records for first admission. In addition, structured self-administered questionnaires and a face-to-face interview were performed assessing occupational status, quality of life, and emotional status at 6 months after stroke. RESULTS: Of the patients in this study, 60.0% returned to work at 6 months after stroke. Sex, age, educational level, and comorbidity level were independent factors related to return to work. The rate of return to work in female patients under 65 years of age was similar to that of male patients 65 years of age or older. Stroke patients who returned to work showed better emotional statuses than those who did not return to work. CONCLUSION: Many stroke patients did not return to work despite functional independence at 6 months after stroke. Based on the results of this study, we suggest providing appropriate vocational rehabilitation for stroke patients and proper education for employers to increase the rate of early return to work in stroke patients. PMID- 26843363 TI - Quantum electric-dipole liquid on a triangular lattice. AB - Geometric frustration and quantum fluctuations may prohibit the formation of long range ordering even at the lowest temperature, and therefore liquid-like ground states could be expected. A good example is the quantum spin liquid in frustrated magnets. Geometric frustration and quantum fluctuations can happen beyond magnetic systems. Here we propose that quantum electric-dipole liquids, analogues of quantum spin liquids, could emerge in frustrated dielectrics where antiferroelectrically coupled electric dipoles reside on a triangular lattice. The quantum paraelectric hexaferrite BaFe12O19 with geometric frustration represents a promising candidate for the proposed electric-dipole liquid. We present a series of experimental lines of evidence, including dielectric permittivity, heat capacity and thermal conductivity measured down to 66 mK, to reveal the existence of an unusual liquid-like quantum phase in BaFe12O19, characterized by itinerant low-energy excitations with a small gap. The possible quantum liquids of electric dipoles in frustrated dielectrics open up a fresh playground for fundamental physics. PMID- 26843362 TI - Poorly soluble cobalt oxide particles trigger genotoxicity via multiple pathways. AB - BACKGROUND: Poorly soluble cobalt (II, III) oxide particles (Co3O4P) are believed to induce in vitro cytotoxic effects via a Trojan-horse mechanism. Once internalized into lysosomal and acidic intracellular compartments, Co3O4P slowly release a low amount of cobalt ions (Co(2+)) that impair the viability of in vitro cultures. In this study, we focused on the genotoxic potential of Co3O4P by performing a comprehensive investigation of the DNA damage exerted in BEAS-2B human bronchial epithelial cells. RESULTS: Our results demonstrate that poorly soluble Co3O4P enhanced the formation of micronuclei in binucleated cells. Moreover, by comet assay we showed that Co3O4P induced primary and oxidative DNA damage, and by scoring the formation of gamma-H2Ax foci, we demonstrated that Co3O4P also generated double DNA strand breaks. CONCLUSIONS: By comparing the effects exerted by poorly soluble Co3O4P with those obtained in the presence of soluble cobalt chloride (CoCl2), we demonstrated that the genotoxic effects of Co3O4P are not simply due to the released Co(2+) but are induced by the particles themselves, as genotoxicity is observed at very low Co3O4P concentrations. PMID- 26843364 TI - Associations between patterns of active commuting and socioeconomic factors in women with fibromyalgia: the al-Andalus project. AB - OBJECTIVES: The aims of this study were to know whether active commuting behaviour differs between fibromyalgia patients and controls, and to test whether active commuting is associated with socioeconomic factors in this population. METHODS: This cross-sectional study included 459 women with fibromyalgia (52.2 years) and 214 female control participants (51.3 years) from Andalusia (southern Spain). Participants reported patterns of active commuting and socioeconomic factors (civil status, accompaniment at home, living with, educational level, and current occupational and professional status). RRESULTS: On the age group <51 years, women with fibromyalgia revealed a significant higher percentage of active commuting for the variable active worker commuters than control group (p<0.05). On the age group >=51 years, control group displayed a significant higher percentage of active commuting for commuting to local shops, super-market and active commuters variables (all, p<0.05). Women with fibromyalgia who lived alone were more active commuters in comparison to either those living accompanied, or living with both partner and children, only partner and only children (all, p<0.05). CONCLUSIONS: The prevalence of active commuting was similar in women with fibromyalgia and controls aged <51 years. However, fibromyalgia participants aged >=51 years displayed differences: fibromyalgia women who lived alone were more active commuters than those living accompanied; family demands were inversely associated with commuting patterns. Policies focused on reducing family demands for fibromyalgia patients (i.e. social help on housework, childcare or overprotection) might facilitate the inclusion of daily active behaviours. PMID- 26843365 TI - Clinical Significance of Laboratory-determined Aspirin Poor Responsiveness After Primary Percutaneous Coronary Intervention. AB - AIMS: The objective of the present substudy was to examine whether aspirin poor/high responsiveness (APR/AHR) is associated with increased rates of major adverse cardiovascular events (MACE) and serious bleeding after primary percutaneous coronary intervention (PPCI). METHODS: We analyzed 961 consecutive ST-elevation acute myocardial infarction patients who underwent PPCI between February 2008 and June 2011. Multiplate analyser (Dynabite, Munich, Germany) was used for the assessment of platelet reactivity. APR/AHR were defined as the upper/lower quintiles of ASPI values, determined 24 h after aspirin loading. APR patients were tailored using 300 mg maintenance dose for 30 days. The co-primary end points at 30 days were: MACE (death, non-fatal infarction, ischemia-driven target vessel revascularization and ischemic stroke) and serious bleeding according to the BARC classification. RESULTS: One hundred and 90 patients were classified as APR, and 193 patients as AHR. At admission, compared with aspirin sensitive patients (ASP), patients with APR had more frequently diabetes, anterior infarction and heart failure, while AHR patients had reduced values of creatine kinase, leukocytes, heart rate and systolic blood pressure. Compared with ASP, the rates of 30-day primary end points did not differ neither in APR group including tailored patients (MACE, adjusted OR 1.02, 95%CI 0.47-2.17; serious bleeding, adjusted OR 1.92, 95%CI 0.79-4.63), nor in patients with AHR (MACE, adjusted OR 1.58, 95%CI 0.71-5.51; serious bleeding, adjusted OR 0.69, 95%CI 0.22-2.12). CONCLUSIONS: The majority of APR patients were suitable for tailoring. Neither APR including tailored patients nor AHR were associated with adverse 30-day efficacy or safety clinical outcomes. PMID- 26843366 TI - Exploring Carbon Nanomaterial Diversity for Nucleation of Protein Crystals. AB - Controlling crystal nucleation is a crucial step in obtaining high quality protein crystals for structure determination by X-ray crystallography. Carbon nanomaterials (CNMs) including carbon nanotubes, graphene oxide, and carbon black provide a range of surface topographies, porosities and length scales; functionalisation with two different approaches, gas phase radical grafting and liquid phase reductive grafting, provide routes to a range of oligomer functionalised products. These grafted materials, combined with a range of controls, were used in a large-scale assessment of the effectiveness for protein crystal nucleation of 20 different carbon nanomaterials on five proteins. This study has allowed a direct comparison of the key characteristics of carbon-based nucleants: appropriate surface chemistry, porosity and/or roughness are required. The most effective solid system tested in this study, carbon black nanoparticles functionalised with poly(ethylene glycol) methyl ether of mean molecular weight 5000, provides a novel highly effective nucleant, that was able to induce crystal nucleation of four out of the five proteins tested at metastable conditions. PMID- 26843367 TI - Going "social" to access experimental and potentially life-saving treatment: an assessment of the policy and online patient advocacy environment for expanded access. AB - Social media is fundamentally altering how we access health information and make decisions about medical treatment, including for terminally ill patients. This specifically includes the growing phenomenon of patients who use online petitions and social media campaigns in an attempt to gain access to experimental drugs through expanded access pathways. Importantly, controversy surrounding expanded access and "compassionate use" involves several disparate stakeholders, including patients, manufacturers, policymakers, and regulatory agencies-all with competing interests and priorities, leading to confusion, frustration, and ultimately advocacy. In order to explore this issue in detail, this correspondence article first conducts a literature review to describe how the expanded access policy and regulatory environment in the United States has evolved over time and how it currently impacts access to experimental drugs. We then conducted structured web searches to identify patient use of online petitions and social media campaigns aimed at compelling access to experimental drugs. This was carried out in order to characterize the types of communication strategies utilized, the diseases and drugs subject to expanded access petitions, and the prevalent themes associated with this form of "digital" patient advocacy. We find that patients and their families experience mixed results, but still gravitate towards the use of online campaigns out of desperation, lack of reliable information about treatment access options, and in direct response to limitations of the current fragmented structure of expanded access regulation and policy currently in place. In response, we discuss potential policy reforms to improve expanded access processes, including advocating greater transparency for expanded access programs, exploring use of targeted economic incentives for manufacturers, and developing systems to facilitate patient information about existing treatment options. This includes leveraging recent legislative attention to reform expanded access through the CURE Act Provisions contained in the proposed U.S. 21st Century Cures Act. While expanded access may not be the best option for the majority of individuals, terminally ill patients and their families nevertheless deserve better processes, policies, and availability to potentially life-changing information, before they decide to pursue an online campaign in the desperate hope of gaining access to experimental drugs. PMID- 26843368 TI - Mutations in the nucleotide binding and hydrolysis domains of Helicobacter pylori MutS2 lead to altered biochemical activities and inactivation of its in vivo function. AB - BACKGROUND: Helicobacter pylori MutS2 (HpMutS2), an inhibitor of recombination during transformation is a non-specific nuclease with two catalytic sites, both of which are essential for its anti-recombinase activity. Although HpMutS2 belongs to a highly conserved family of ABC transporter ATPases, the role of its ATP binding and hydrolysis activities remains elusive. RESULTS: To explore the putative role of ATP binding and hydrolysis activities of HpMutS2 we specifically generated point mutations in the nucleotide-binding Walker-A (HpMutS2-G338R) and hydrolysis Walker-B (HpMutS2-E413A) domains of the protein. Compared to wild-type protein, HpMutS2-G338R exhibited ~2.5-fold lower affinity for both ATP and ADP while ATP hydrolysis was reduced by ~3-fold. Nucleotide binding efficiencies of HpMutS2-E413A were not significantly altered; however the ATP hydrolysis was reduced by ~10-fold. Although mutations in the Walker-A and Walker-B motifs of HpMutS2 only partially reduced its ability to bind and hydrolyze ATP, we demonstrate that these mutants not only exhibited alterations in the conformation, DNA binding and nuclease activities of the protein but failed to complement the hyper-recombinant phenotype displayed by mutS2-disrupted strain of H. pylori. In addition, we show that the nucleotide cofactor modulates the conformation, DNA binding and nuclease activities of HpMutS2. CONCLUSIONS: These data describe a strong crosstalk between the ATPase, DNA binding, and nuclease activities of HpMutS2. Furthermore these data show that both, ATP binding and hydrolysis activities of HpMutS2 are essential for the in vivo anti-recombinase function of the protein. PMID- 26843369 TI - Grain Size Distribution and Health Risk Assessment of Metals in Outdoor Dust in Chengdu, Southwestern China. AB - A total of 27 outdoor dust samples from roads, parks, and high spots were collected and analyzed to investigate the contamination of 11 metals (Cr, Mn, Co, Ni, Cu, Zn, As, Sr, Cd, Sb, and Pb) in Chengdu, China. The results showed that the samples from the high spots exhibited the highest heavy metal level compared with those from the roads and the parks, except for Ni, Cu, and Pb. The dust was classified into five grain size fractions. The mean loads of each grain size fraction of 11 determined metals displayed similar distribution, and the contribution of median size (63-125, 125-250, 250-500 MUm) fractions accounted for more than 70% of overall heavy metal loads. The health risk posed by the determined metals to human via dust ingestion, dermal contact, and inhalation was investigated. Oral and respiratory bioaccessible parts of the metals in dust were extracted using simulated stomach solution and composite lung serum. The mean bioaccessibilities of 11 investigated metals in the gastric solution were much higher than those in the composite lung serum, especially Zn, Cd, and Pb. Ingestion was the most important exposure pathway with percentage greater than 70% for both children and adults. Risk evaluation results illustrated that children in Chengdu might suffer noncarcinogenic risk when exposed to outdoor dust. Given that the cancer risk values of Pb and Cr larger than 1 * 10(-4), potential carcinogenic risk might occur for Chengdu residents through outdoor dust intake. PMID- 26843370 TI - NGS in argininosuccinic aciduria detects a mutation (D145G) which drives alternative splicing of ASL: a case report study. AB - BACKGROUND: Argininosuccinic aciduria (ASAuria; OMIM 207900) is a rare autosomal recessive heterogeneous urea cycle disorder, which leads to the accumulation of argininosuccinic acid in the blood and urine. We aimed to perform genetic test to the patient and help clinician to diagnose precisely. CASE PRESENTATION: In this study, we use next generation sequencing (NGS) and exon trapping to analysis the family members. We identified compound heterozygous mutations of the argininosuccinate lyase (ASL) gene in a Chinese Han ASAuria patient. The c.434A>G (p.(D145G)) mutation in exon 5 was shown by exon trapping to select for the formation of an alternative transcript deleted for exon 5. The c.1366C>T (p.(R456W)) mutation had been previously reported in an Italian patient. CONCLUSIONS: This is the first report of a missense mutation driving alternative splicing which results in the loss of exon 5 in ASAuria. This study also demonstrates the value of NGS in the identification of mutations and molecular diagnosis for ASAuria families. PMID- 26843372 TI - An observational study of the direct costs related to hospital admissions, mortality and premature death associated with liver disease in Portugal. AB - BACKGROUND: Liver disease, one of the most common causes of hospitalization worldwide, is particularly prevalent in Europe. This study aimed to determine the number of hospital discharges and admissions, mortality, premature death and costs associated with liver disease from the perspective of the National Health Service in Portugal. METHODS: A descriptive, retrospective analysis of data from 97 hospitals between 2000 and 2008, and mortality data for 2011 collected from the Portuguese National Institute of Statistics. The 9th and 10th revisions of the international classification of diseases were used to establish diagnoses. National data on demographics, average length of stay, in-patient mortality and direct costs associated with hospital admissions and liver transplantation were compared for the most common liver diseases. Mortality and premature death were compared using the potential years of life lost (PYLL) index. RESULTS: The annual mean number of discharges for liver disease was 11,503 between 2000 and 2008. Most cases of liver disease were diagnosed in men (70.4 %) and the prevalence of liver disease peaked in patients aged from 20 to 64 years (60.7 %). Alcoholic cirrhosis was the most frequent liver-disease diagnosis leading to discharge (38.6 %). In addition, alcoholic cirrhosis emerged as the main cost-driver, accounting for ?26,818,930 (42.6 %) of the total cost imposed by liver disease. Overall, chronic hepatic disease was the 10th most common cause of mortality in Portugal in 2011, causing 21.8 deaths per 100,000. Chronic hepatic disease and hepatocellular carcinoma are even more important causes of premature death, ranking third based on PYLL. CONCLUSION: In 2011, liver disease was the 10th most common cause of death and the third most important cause of premature death in Portugal. Alcohol cirrhosis was the leading cause of liver-related hospital admissions between 2001 and 2008. It appears that liver disease imposes a considerable social and economic burden on Portugal. Our results suggest that educational, legislative and therapeutic interventions to prevent morbidity, mortality and premature death from liver disease are urgently required to minimise the economic and clinical burdens. PMID- 26843373 TI - Better than treated as usual: Transcranial magnetic stimulation augmentation in selective serotonin reuptake inhibitor-refractory obsessive-compulsive disorder, mini-review and pilot open-label trial. AB - OBJECTIVE: 1 Hz repetitive transcranial magnetic stimulation (rTMS) over the supplementary motor area has been shown to be effective in a subset of obsessive compulsive disorder (OCD) subjects, yet these results are still to be confirmed. This preliminary study compares the efficacy of augmentation with 1 Hz rTMS over the supplementary motor area and the usual augmentation treatment (TAU; treated as usual) with antipsychotics in a sample of selective serotonin reuptake inhibitor (SSRI)-refractory OCD patients. METHOD: Fifty SSRI-refractory OCD patients consecutively admitted were studied: 25 were treated with a three-week trial of 1Hz, bilateral rTMS over the supplementary motor area and 25 with antipsychotic drugs. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS; primary outcome measure), Hamilton Depression and Hamilton Anxiety scales were administered at first, second and third week of treatment. RESULTS: Y-BOCS showed a statistically significant time effect from the baseline to the third week, with a 68% of responders (Y-BOCS score reduction of ? 25%), in comparison with 24.0% in the TAU group. In the rTMS group, 17.6% of patients achieved remission. CONCLUSIONS: 1 Hz rTMS over the supplementary motor area appeared to be effective in approximately 2/3 of SSRI-refractory OCD subjects, whereas in the TAU group only 1/4 of subjects were responders. The supplementary motor area might be a new target area to be further explored with neuromodulation for OCD treatment. PMID- 26843371 TI - Site-specific mutagenesis of yeast 2-Cys peroxiredoxin improves heat or oxidative stress tolerance by enhancing its chaperone or peroxidase function. AB - Yeast peroxiredoxin II (yPrxII) is an antioxidant enzyme that plays a protective role against the damage caused by reactive oxygen species (ROS) in Saccharomyces cerevisiae. This enzyme consists of 196 amino acids containing 2-Cys Prx with highly conserved two active cysteine residues at positions 48 and 171. The yPrxII has dual enzymatic functions as a peroxidase and molecular chaperone. To understand the effect of additional cysteine residues on dual functions of yPrxII, S79C-yPrxII and S109C-yPrxII, the substitution of Ser with Cys residue at 79 and 109 positions, respectively, was generated. S109C-yPrxII and S79C-yPrxII showed 3.7- and 2.7-fold higher chaperone and peroxidase activity, respectively, than the wild type (WT). The improvement in enzyme activity was found to be closely associated with structural changes in proteins. S109C-yPrxII had increased beta-sheet in its secondary structure and formed high-molecular-weight (HMW) as well as low-molecular-weight (LMW) complexes, but S79C-yPrxII formed only LMW complexes. HMW complexes predominantly exhibited a chaperone function, and LMW complexes showed a peroxidase function. In addition, transgenic yeast cells over-expressing Cys-substituted yPrxII showed greater tolerance against heat and oxidative stress compared to WT-yPrxII. PMID- 26843374 TI - Terrilactibacillus laevilacticus gen. nov., sp. nov., isolated from soil. AB - A Gram-stain-positive, catalase-positive, facultatively anaerobic, spore-forming, rod-shaped bacterium, strain NK26-11T, was isolated from soil in Thailand. This strain produced d-lactic acid from glucose homofermentatively, and grew at 20-45 degrees C and pH 5-8.5. The cell-wall peptidoglycan contained meso-diaminopimelic acid. The major respiratory quinone was menaquinone 7 (MK-7), the DNA G+C content was 42.6 mol%, and the major cellular fatty acids were anteiso-C15 : 0 and anteiso-C17 : 0. On the basis of 16S rRNA gene sequences analysis, strain NK26 11T was closely related to Bacillus solimangrovi JCM 18994T (93.89 % 16S rRNA gene sequence similarity), Pullulanibacillus naganoensis LMG 12887T (93.32 %), Sporolactobacillus inulinus NRIC 1133T (92.99 %), Tuberibacillus calidus JCM 13397T (92.98 %) and Thalassobacillus devorans DSM 16966T ( < 90.93 %). Strain NK26-11T could be clearly distinguished from the closely related genera based on phenotypic characteristics and DNA G+C content, and thus represents a novel species of a new genus between the Bacillus and Sporolactobacillus cluster, for which the name Terrilactibacillus laevilacticus gen. nov., sp. nov. is proposed. The type strain of the type species is NK26-11T ( = LMG 27803T = TISTR 2241T = PCU 335T). PMID- 26843375 TI - Recurrent Richter's Transformation Presenting With a Penile Ulcer. PMID- 26843377 TI - Centralized services and large patient volumes are clinical necessities for a better outcome in pediatric brain tumors. PMID- 26843378 TI - Introduction to the special issue on teacher knowledge from an international perspective. PMID- 26843376 TI - Presenting characteristics of children who required neurosurgical intervention for head injury. AB - PURPOSE: The purpose of this study is to describe the presenting characteristics of a large group of children who required neurosurgical intervention (NSI) following a head injury and to retrospectively assess which of the criteria for imaging from Children's Head Injury Algorithm for the Prediction of Important Clinical Events (CHALICE), Pediatric Emergency Care Applied Research Network (PECARN), and Canadian Assessment of Tomography for Childhood Head Injury (CATCH) clinical decision rules (CDRs) were met by these patients. STUDY DESIGN: We retrospectively reviewed all patients undergoing NSI following a head injury, between 2000 and 2008, at a large tertiary pediatric trauma center. We excluded patients having non-accidental injury, other neurosurgical interventions, penetrating injuries, and patients with incomplete data. To those who presented initially with mild head injury (GCS 14-15), we retrospectively applied the criteria for imaging of the CHALICE, PECARN, and CATCH CDRs. RESULTS: Out of 289 patients undergoing NSI, 182 met inclusion criteria and comprised our cohort. Of the 72 (39.6 %) with mild head injury (GCS 14-15), 71 (98.6 %) met at least one criteria for imaging from each of the three CDRs, including severe mechanism of injury (68, 94.4 %), clinically evident skull fracture (35, 48.6 %), neurological deficit (19, 26.3 %), or severe headache (6, 8.3 %). Of the 182 patients in the entire cohort, only 1 (0.5 %) did not present with an obvious indication for CT on all three CDRs. CONCLUSIONS: In a large sample of children requiring NSI after head trauma, the vast majority met CT criteria listed in each of the three CDRs. The most common indication for CT was a severe mechanism of injury. This, combined with clinically evident skull fracture, neurological deficit, and severe headache, identifies almost all patients requiring NSI. PMID- 26843379 TI - Mild Depressive Symptoms Among Americans in Relation to Physical Activity, Current Overweight/Obesity, and Self-Reported History of Overweight/Obesity. AB - PURPOSE: Overweight/obese individuals are at an increased risk for depression with some evidence of a bidirectional association. The preventative effects of physical activity among overweight/obese individuals have been well documented; however, less is known on how the duration of overweight/obesity alters the association with negative health outcomes. Therefore, the purpose of this investigation was to determine how the classification, and more specifically duration, of overweight/obesity alters the association between physical activity and depressive symptoms. METHODS: The 2005-2006 National Health and Nutrition Examination Survey (NHANES) data were used (n = 764), and individuals were divided into six mutually exclusive groups based on physical activity status, weight classification (measured BMI), and duration of weight classification (assessed via recall). Multivariable linear and logistic regression analyses were computed to examine odds of depressive symptoms (patient health questionnaire (PHQ)-9) among groups. RESULTS: After adjusting for covariates, only individuals who were inactive and overweight/obese at the examination and 10 years prior were at an increased odds of depressive symptoms in comparison to those who were active and normal weight (odds ratio (OR) = 2.40; 95 % confidence interval (CI) 1.03, 5.61; p = 0.04). CONCLUSION: Physical activity appeared to ameliorate the association with depressive symptoms independent of overweight/obesity classification or duration. The cyclic nature of overweight/obesity and depression (i.e., bidirectional association) appears to increase the odds of depression as the length of overweight/obesity is increased. These results provide support for clinicians to assess not only their clients' current BMI but also the duration in which they have been at a certain weight classification and to further promote physical activity as a preventative measure against depressive symptoms. PMID- 26843381 TI - Erratum to: Cariprazine: First Global Approval. PMID- 26843380 TI - Substitution of SF-36 by SF-12 Among Hong Kong Chinese Older Adults: Secondary Analysis of Randomized Controlled Trials. AB - PURPOSE: This study aims to examine the appropriateness of substituting the Short Form 36 (SF-36) by its shortened version (SF-12) in measuring health-related quality of life (HRQoL) in older Chinese population. METHODS: Secondary analysis of two transitional care management programs, conducted from 2009 to 2012, were analyzed (n = 1188, aged 60-97). Participants were discharged patients with respiratory disease, type 2 diabetes, cardiac disease, and renal disease, and were classified according to number of chronic diseases. SF-36 was administered at baseline and 4-week follow-up. RESULTS: Both overestimations and underestimations of HRQoL by SF-12 were found. Most domain scores of SF-36 and SF 12 were highly correlated (Spearman correlation (rho) > 0.85), with the exception of General Health (rho = 0.64) and Vitality subscales (rho = 0.82). Multiple linear regression adjusted for demographic characteristics showed that the four out of eight domains of SF-36 and SF-12 were equivalent in measuring the difference across numbers of chronic diseases (all p < 0.05). Paired sample t tests in 989 (83.2 %) who completed the SF-36 survey 4 weeks after baseline showed that SF-12 overestimated the 4-week changes in most of the domains. CONCLUSIONS: The use of the Chinese version of SF-12v2 for reporting the change over time in quality of life among medical patients after hospital discharge may need to be interpreted with caution. The SF-12 tends to underestimate the difference when compared with the SF-36. PMID- 26843383 TI - Reassessing the risk of natalizumab-associated PML. AB - The risk algorithm for natalizumab-associated PML was first established in 2012 using the observations that JC virus antibody status, prolonged duration of natalizumab therapy (>2 years), and prior exposure to immunosuppressive therapy increased the risk for the disease. Prior to the publication of Biogen's algorithm, a risk algorithm was created by Fox and Rudick using an Excel spreadsheet in order to address the concerns of their patients. Applying the most recently available data regarding natalizumab-associated PML, the risk assessments for PML were recalculated. The current numbers indicate substantially higher risks for PML in 2015 than in 2012. Our calculations suggest that an individual having all three risk factors has an approximately 1 in 44 chance of developing PML. PMID- 26843382 TI - Frequency of varicella zoster virus DNA in human adrenal glands. AB - Varicella zoster virus (VZV) becomes latent in ganglionic neurons derived from neural crest cells. Because the adrenal gland also contains medullary chromaffin cells of neural crest origin, we examined human adrenal glands and medullary chromaffin cell tumors (pheochromocytomas) for VZV and herpes simplex virus type 1 (HSV-1). We found VZV, but not HSV-1, DNA in 4/63 (6 %) normal adrenal glands. No VZV transcripts or antigens were detected in the 4 VZV DNA-positive samples. No VZV or HSV-1 DNA was found in 21 pheochromocytomas. PMID- 26843384 TI - HIV-1 transgenic rats display mitochondrial abnormalities consistent with abnormal energy generation and distribution. AB - With the advent of the combination antiretroviral therapy era (cART), the development of AIDS has been largely limited in the USA. Unfortunately, despite the development of efficacious treatments, HIV-1-associated neurocognitive disorders (HAND) can still develop, and as many HIV-1 positive individuals age, the prevalence of HAND is likely to rise because HAND manifests in the brain with very low levels of virus. However, the mechanism producing this viral disorder is still debated. Interestingly, HIV-1 infection exposes neurons to proteins including Tat, Nef, and Vpr which can drastically alter mitochondrial properties. Mitochondrial dysfunction has been posited to be a cornerstone of the development of numerous neurodegenerative diseases. Therefore, we investigated mitochondria in an animal model of HAND. Using an HIV-1 transgenic rat model expressing seven of the nine HIV-1 viral proteins, mitochondrial functional and proteomic analysis were performed on a subset of mitochondria that are particularly sensitive to cellular changes, the neuronal synaptic mitochondria. Quantitative mass spectroscopic studies followed by statistical analysis revealed extensive proteome alteration in this model paralleling mitochondrial abnormalities identified in HIV-1 animal models and HIV-1-infected humans. Novel mitochondrial protein changes were discovered in the electron transport chain (ETC), the glycolytic pathways, mitochondrial trafficking proteins, and proteins involved in various energy pathways, and these findings correlated well with the function of the mitochondria as assessed by a mitochondrial coupling and flux assay. By targeting these proteins and proteins upstream in the same pathway, we may be able to limit the development of HAND. PMID- 26843387 TI - Letter to the editor in response to Mawby et al. A UK experience of daycase cochlear implant surgery. PMID- 26843386 TI - Serum concentrations of 25-hydroxyvitamin D and its association with bone mineral density and serum parathyroid hormone levels during winter in urban males from Guiyang, Southwest China. AB - Serum vitamin D (25-hydroxyvitamin D (25OHD)) may influence serum parathyroid hormone (PTH) levels and bone mineral density (BMD). In the present study, we assessed serum 25OHD concentration and its association with PTH and BMD in urban males from Guiyang (N26.57 degrees ), the capital city of Guizhou province, Southwest China. We recruited 634 males aged >20 years from the Guiyang Health Measures Survey, and stratified them into three groups according to age: young (20-39 years), middle aged (40-59 years) and older (60-79 years). We measured serum concentrations of 25OHD, PTH levels and BMD of the lumbar spine (L1-L4), femoral neck and total hip. In addition, we also explored the relationship between 25OHD and lifestyle, socio-economic characteristics and medical history by applying covariance analysis and locally weighted regression plots. The results showed that serum 25OHD was 75 nmol/l in 12.6 % of the subjects. Higher level of serum PTH was detected in relation to lower concentrations of serum 25OHD up to 50 nmol/l. A negative correlation between serum 25OHD and PTH concentrations was observed (r -0.207, P=0.003). Mean concentration of serum PTH increased gradually and plateaued while concentrations of serum 25OHD decreased to 50 nmol/l. Gradual increase in serum PTH was observed as 25OHD concentration was <25 nmol/l (P=0.004). BMD values at all sites were greater in the higher serum 25OHD concentration group. This study shows that low concentrations of serum 25OHD were common in males, and bone health was likely to be improved when serum 25OHD values were between 30 and 50 nmol/l. PMID- 26843388 TI - Heads or tails: cell biological secrets of the spermatozoon revealed. PMID- 26843385 TI - Overexpression of thyroid hormone receptor beta1 altered thyroid hormone-mediated regulation of herpes simplex virus-1 replication in differentiated cells. AB - Thyroid hormone (T3) has been suggested to play a role in herpes simplex virus 1 (HSV-1) replication. It was previously reported that HSV-1 replication was suppressed by T3 in mouse neuroblastoma cells overexpressing thyroid hormone receptor beta1 (TRbeta1). Using a human neuro-endocrine cells LNCaP differentiated by androgen deprivation, HSV-1 replication was active but decreased by T3 at very low moi, probably due to low copy of TRbeta1. In this study, a recombinant HSV-1 was constructed expressing TRbeta1 (HSV-1/TRbeta1). Infection of Vero cells (very little TRbeta1 expression) with HSV-1/TRbeta1 exhibited increased replication in the presence of T3 compared to the counterpart without TRbeta1 overexpression. Interestingly, HSV-1/TRbeta1 infection of differentiated LNCaP cells showed strong suppression of viral replication by T3 and the removal of hormone did not fully reversed the suppression as was observed in parent virus. Quantitative analyses indicated that ICP0 expression was blocked using HSV-1/TRbeta1 for infection during T3 washout, suggesting that overexpression of TRbeta1 is likely to delay its inhibitory effect on viral gene expression. Together these results emphasized the importance of TRbeta1 in the regulation of HSV-1 replication in differentiated environment with neuronal phenotype. PMID- 26843389 TI - Artificial shrinkage of blastocoel using a laser pulse prior to vitrification improves clinical outcome. AB - PURPOSE: Blastocysts contain a large amount of fluid in the blastocoel, which may pose a risk for ice crystal formation during vitrification. This study aimed to evaluate the effectiveness of laser-induced artificial shrinkage of blastocoel before vitrification on clinical outcome. METHODS: Patients were divided into two groups: a control group with untreated, expanded blastocysts (n = 115) and a study group with blastocoel artificially eliminated by a laser pulse prior to vitrification (n = 309). Blastocyst survival, clinical pregnancy, and implantation rates were compared. RESULT(S): The survival rate was significantly higher in the study group compared with the control group (97.3 and 74.9 %, respectively; p > 0.01). The clinical pregnancy and implantation rates of the study group were significantly higher (p < 0.01) than that of the control group (clinical pregnancy, 67.2 vs. 41.1 %; implantation, 39.1 vs. 24.5 %. CONCLUSION(S): This study demonstrated that the removal of blastocoel fluid before vitrification by laser pulse of in vitro-produced human blastocysts significantly improves blastocyst survival, clinical pregnancy, and implantation rates. PMID- 26843390 TI - Comparing blastocyst quality and live birth rates of intravaginal culture using INVOcellTM to traditional in vitro incubation in a randomized open-label prospective controlled trial. AB - PURPOSE: The purpose of this study is to to compare the efficacy of intravaginal culture (IVC) of embryos in INVOcellTM (INVO Bioscience, MA, USA) to traditional in vitro fertilization (IVF) incubators in a laboratory setting using a mild pre determined stimulation regimen based solely on anti-mullerian hormone (AMH) and body weight with minimal ultrasound monitoring. The primary endpoint examined was total quality blastocysts expressed as a percentage of total oocytes placed in incubation. Secondary endpoints included percentage of quality blastocysts transferred, pregnancy, and live birth rates. METHODS: In this prospective randomized open-label controlled single-center study, 40 women aged <38 years of age with a body mass index (BMI) of <36 and an AMH of 1-3 ng/mL were randomized prior to trigger to receive either IVC or IVF. Controlled ovarian stimulation was administered with human menopausal gonadotropin (hMG) in a fixed gonadotropin releasing hormone (GnRH) agonist cycle based solely on AMH and body weight. A single ultrasound-monitoring visit was performed on the 10th day of stimulation. One or two embryos were transferred following 5 days of culture. RESULTS: IVF produced a greater percentage of total quality embryos as compared to IVC (50.6 vs. 30.7 %, p = 0.0007, respectively). There was no significant difference between in IVF and IVC in the percentage of quality blastocysts transferred (97.5 vs. 84.9 %, p = 0.09) or live birth rate (60 % IVF, 55 % IVC). CONCLUSIONS: IVF was shown to be superior to IVC in creating quality blastocysts. However, both IVF and IVC produced identical blastocysts for transfer resulting in similar live birth rates. IVC using INVOcellTM is effective and may broaden access to fertility care in selected patient populations by ameliorating the need for a traditional IVF laboratory setting. Further studies will help elucidate the potential physiological, psychological, geographic, and financial impact of IVC on the delivery of fertility care. PMID- 26843391 TI - The poly(A)-binding protein genes, EPAB, PABPC1, and PABPC3 are differentially expressed in infertile men with non-obstructive azoospermia. AB - PURPOSE: Azoospermia is one of the major causes of male infertility and is basically classified into obstructive (OA) and non-obstructive azoospermia (NOA). The molecular background of NOA still largely remains elusive. It has been shown that the poly(A)-binding proteins (PABPs) essentially play critical roles in stabilization and translational control of the mRNAs during spermatogenesis. METHODS: In the present study, we aim to evaluate expression levels of the PABP genes, EPAB, PABPC1, and PABPC3, in the testicular biopsy samples and in the isolated spermatocyte (SC) and round spermatid (RS) fractions obtained from men with various types of NOA including hypospermatogenesis (hyposperm), RS arrest, SC arrest, and Sertoli cell-only syndrome (SCO). RESULTS: In the testicular biopsy samples, both PABPC1 and PABPC3 mRNA expressions were gradually decreased from hyposperm to SCO groups (P < 0.05), whereas there was no remarkable difference for the EPAB expression among groups. The expression levels of cytoplasmically localized PABPC1 and PABPC3 proteins dramatically reduced from hyposperm to SCO groups (P < 0.05). In the isolated SC and RS fractions, the EPAB, PABPC1, and PABPC3 mRNA expressions were gradually decreased from hyposperm to SC arrest groups (P < 0.05). Similarly, both PABPC1 and PABPC3 proteins were expressed at higher levels in the SC and RS fractions from hyposperm group when compared to the SC and RS fractions from either RS arrest or SC arrest group (P < 0.05). CONCLUSION: Our findings suggest that observed significant alterations in the PABPs expression may have an implication for development of different NOA forms. PMID- 26843392 TI - What about superfertility, decidualization, and natural selection? PMID- 26843393 TI - Embryo banking among women diagnosed with cancer: a pilot population-based study in New York, Texas, and Illinois. AB - PURPOSE: The purpose of the present study is to estimate the proportion of women with cancer who return to use the embryos that they have banked and to compare this proportion to that of women without cancer who bank embryos. METHODS: This is a cohort study of three groups of women from New York, Texas, and Illinois who used embryo banking in their first assisted reproductive technology (ART) treatment cycle: two groups with cancer (222 women without an infertility diagnosis and 48 women with an infertility diagnosis) and a control group without cancer (68 women with the infertility diagnosis of male factor only). Women were included only if their first ART cycle reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) occurred between 2004 and 2009. Cancer cases were identified from each State Cancer Registry from 5 years prior to initiation of ART treatment to 6 months post initiation; mean follow-up after the first ART cycle was 2.0 years. RESULTS: Women with cancer without an infertility diagnosis returned for a subsequent ART cycle at a lower rate (10.8 %) than those with an infertility diagnosis (31.3 %, p = 0.0010) or the control group (85.3 %, p < 0.0001). Among those who returned for a subsequent cycle, women with cancer waited a longer time to return (14.3 months without an infertility diagnosis and 8.3 months with an infertility diagnosis, p = 0.13) compared to the control group (2.8 months, p = 0.0007). The live birth rate among women who did not utilize embryo banking in their second cycle did not differ significantly across the three study groups, ranging from 25.0 and 42.9 % for women with cancer with and without an infertility diagnosis, respectively, to 36.2 % for women in the control group. CONCLUSIONS: Women with cancer without an infertility diagnosis are either less likely to return for subsequent treatment or will wait a longer time to return than women with an infertility diagnosis or those that do not have cancer. A longer-term study is necessary to assess whether these women return to use their frozen embryos after cancer treatment or are able to spontaneously conceive and if those subsequent pregnancies are adversely affected by the cancer diagnosis or therapy. PMID- 26843395 TI - Financial Strain and Mental Health Among Older Adults During the Great Recession. AB - OBJECTIVES: The economic recession has garnered the interest of many scholars, with much attention being drawn to how the recession has affected labor force participation, household wealth, and even retirement decisions. Certainly, the Great Recession has influenced the financial well-being of older adults, but has it had discernible effects on mental health? METHOD: This study draws on 5,366 respondents from the Health and Retirement Study (2006-2010) to examine objective and subjective measures of financial well-being in the period surrounding the Great Recession. Guided by cumulative inequality theory, this research investigates whether the economic downturn contributed to worsening anxiety and depressive symptoms over a 4-year period. RESULTS: Results from linear fixed effects models reveal that decreases in objective financial resources were associated with increased financial strain during the Great Recession. Unlike the objective indicators, however, financial strain was a strong and robust predictor of worsening mental health between 2006 and 2010. DISCUSSION: Building on prior research, this study elucidates the factors that shape financial strain and provides evidence that the Great Recession not only affected the financial well being of older adults but also had adverse effects on mental health. PMID- 26843396 TI - Social Inequality and Visual Impairment in Older People. AB - Objectives: Visual impairment is the leading cause of age-related disability, but the social patterning of loss of vision in older people has received little attention. This study's objective was to assess the association between social position and onset of visual impairment, to empirically evidence health inequalities in later life. Method: Visual impairment was measured in 2 ways: self-reporting fair vision or worse (moderate) and self-reporting poor vision or blindness (severe). Correspondingly, 2 samples were drawn from the English Longitudinal Study on Ageing (ELSA). First, 7,483 respondents who had good vision or better at Wave 1; second, 8,487 respondents who had fair vision or better at Wave 1. Survival techniques were used. Results: Cox proportional hazards models showed wealth and subjective social status (SSS) were significant risk factors associated with the onset of visual impairment. The risk of onset of moderate visual impairment was significantly higher for the lowest and second lowest wealth quintiles, whereas the risk of onset of severe visual impairment was significantly higher for the lowest, second, and even middle wealth quintiles, compared with the highest wealth quintile. Independently, lower SSS was associated with increased risk of onset of visual impairment (both measures), particularly so for those placing themselves on the lowest rungs of the social ladder. Discussion: The high costs of visual impairment are disproportionately felt by the worst off elderly. Both low wealth and low SSS significantly increase the risk of onset of visual impairment. PMID- 26843394 TI - Do morphokinetic data sets inform pregnancy potential? AB - PURPOSE: The aim of this study was to create a model to predict the implantation of transferred embryos based on information contained in the morphokinetic parameters of time-lapse monitoring. METHODS: An analysis of time-lapse recordings of 410 embryos transferred in 343 cycles of in vitro fertilization (IVF) treatment was performed. The study was conducted between June 2012 and November 2014. For each embryo, the following data were collected: the duration of time from the intracytoplasmic sperm injection (ICSI) procedure to further division for two, three, four, and five blastomeres, time intervals between successive divisions, and the level of fragmentation assessed in successive time points. Principal component analysis (PCA) and logistic regression were used to create a predictive model. RESULTS: Based on the results of principal component analysis and logistic regression analysis, a predictive equation was constructed. Statistically significant differences (p < 0.001) in the size of the created parameter between the implanted group (the median value: Me = -5.18 and quartiles: Q 1= -5.61; Q 3 = -4.79) and the non-implanted group (Me = -5.69, Q 1 = -6.34; Q 3 = -5.16) were found. A receiver operating characteristic (ROC) curve constructed for the considered model showed the good quality of this predictive equation. The area under the ROC curve was AUC = 0.70 with a 95% confidence interval (0.64, 0.75). The presented model has been validated on an independent data set, illustrating that the model is reliable and repeatable. CONCLUSIONS: Morphokinetic parameters contain information useful in the process of creating pregnancy prediction models. However, embryo quality is not the only factor responsible for implantation, and, thus, the power of prediction of the considered model is not as high as in models for blastocyst formation. Nevertheless, as illustrated by the results of this study, the application of advanced data-mining methods in reproductive medicine allows one to create more accurate and useful models. PMID- 26843397 TI - The effects of asymmetric competition on the life history of Trinidadian guppies. AB - The effects of asymmetric interactions on population dynamics has been widely investigated, but there has been little work aimed at understanding how life history parameters like generation time, life expectancy and the variance in lifetime reproductive success are impacted by different types of competition. We develop a new framework for incorporating trait-mediated density-dependence into size-structured models and use Trinidadian guppies to show how different types of competitive interactions impact life history parameters. Our results show the degree of symmetry in competitive interactions can have dramatic effects on the speed of the life history. For some vital rates, shifting the competitive superiority from small to large individuals resulted in a doubling of the generation time. Such large influences of competitive symmetry on the timescale of demographic processes, and hence evolution, highlights the interwoven nature of ecological and evolutionary processes and the importance of density-dependence in understanding eco-evolutionary dynamics. PMID- 26843398 TI - Stability and distribution of predator-prey systems: local and regional mechanisms and patterns. AB - Explaining the coexistence and distribution of species in time and space remains a fundamental challenge. While species coexistence depends on both local and regional mechanisms, it is sometimes unclear which role each mechanism takes in a given ecosystem. Consequently, it is very hard to predict the response of the ecosystem to environmental changes. Here, we develop a model to study spatial patterns of coexistence, focusing on predator-prey and host-parasite populations. We show, both theoretically and empirically, that these systems may exhibit both local and regional patterns and mechanisms of coexistence. Changes in environmental parameters, such as spatial connectivity, may lead to a transition from regional to local coexistence or it may lead directly to extinction, depending on demographic parameters. This demonstrates the importance of simultaneously analysing interacting mechanisms that act at different spatial scales to understand the response of ecosystems to environmental changes. PMID- 26843399 TI - Host dispersal as the driver of parasite genetic structure: a paradigm lost? AB - Understanding traits influencing the distribution of genetic diversity has major ecological and evolutionary implications for host-parasite interactions. The genetic structure of parasites is expected to conform to that of their hosts, because host dispersal is generally assumed to drive parasite dispersal. Here, we used a meta-analysis to test this paradigm and determine whether traits related to host dispersal correctly predict the spatial co-distribution of host and parasite genetic variation. We compiled data from empirical work on local adaptation and host-parasite population genetic structure from a wide range of taxonomic groups. We found that genetic differentiation was significantly lower in parasites than in hosts, suggesting that dispersal may often be higher for parasites. A significant correlation in the pairwise genetic differentiation of hosts and parasites was evident, but surprisingly weak. These results were largely explained by parasite reproductive mode, the proportion of free-living stages in the parasite life cycle and the geographical extent of the study; variables related to host dispersal were poor predictors of genetic patterns. Our results do not dispel the paradigm that parasite population genetic structure depends on host dispersal. Rather, we highlight that alternative factors are also important in driving the co-distribution of host and parasite genetic variation. PMID- 26843400 TI - Spatial distribution and cluster analysis of risky sexual behaviours and STDs reported by Chinese adults in Guangzhou, China: a representative population-based study. AB - OBJECTIVES: To assess associations between residences location, risky sexual behaviours and sexually transmitted diseases (STDs) among adults living in Guangzhou, China. METHODS: Data were obtained from 751 Chinese adults aged 18-59 years in Guangzhou, China, using stratified random sampling by using spatial epidemiological methods. Face-to-face household interviews were conducted to collect self-report data on risky sexual behaviours and diagnosed STDs. Kulldorff's spatial scan statistic was implemented to identify and detect spatial distribution and clusters of risky sexual behaviours and STDs. The presence and location of statistically significant clusters were mapped in the study areas using ArcGIS software. RESULTS: The prevalence of self-reported risky sexual behaviours was between 5.1% and 50.0%. The self-reported lifetime prevalence of diagnosed STDs was 7.06%. Anal intercourse clustered in an area located along the border within the rural-urban continuum (p=0.001). High rate clusters for alcohol or other drugs using before sex (p=0.008) and migrants who lived in Guangzhou <1 year (p=0.007) overlapped this cluster. Excess cases for unprotected sex (p=0.031) overlapped the cluster for college students (p<0.001). Five of nine (55.6%) students who had sexual experience during the last 12 months located in the cluster of unprotected sex. CONCLUSIONS: Short-term migrants and college students reported greater risky sexual behaviours. Programmes to increase safer sex within these communities to reduce the risk of STDs are warranted in Guangzhou. Spatial analysis identified geographical clusters of risky sexual behaviours, which is critical for optimising surveillance and targeting control measures for these locations in the future. PMID- 26843401 TI - Prediction of Chlamydia trachomatis infection to facilitate selective screening on population and individual level: a cross-sectional study of a population-based screening programme. AB - OBJECTIVES: To develop prediction models for Chlamydia trachomatis (Ct) infection with different levels of detail in information, that is, from readily available data in registries and from additional questionnaires. METHODS: All inhabitants of Rotterdam and Amsterdam aged 16-29 were invited yearly from 2008 until 2011 for home-based testing. Their registry data included gender, age, ethnicity and neighbourhood-level socioeconomic status (SES). Participants were asked to fill in a questionnaire on education, sexually transmitted infection history, symptoms, partner information and sexual behaviour. We developed prediction models for Ct infection using first-time participant data-including registry variables only and with additional questionnaire variables-by multilevel logistic regression analysis to account for clustering within neighbourhoods. We assessed the discriminative ability by the area under the receiver operating characteristic curve (AUC). RESULTS: Four per cent (3540/80 385) of the participants was infected. The strongest registry predictors for Ct infection were young age (especially for women) and Surinamese, Antillean or sub-Saharan African ethnicity. Neighbourhood-level SES was of minor importance. Strong questionnaire predictors were low to intermediate education level, ethnicity of the partner (non-Dutch) and having sex with casual partners. When using a prediction model including questionnaire risk factors (AUC 0.74, 95% CI 0.736 to 0.752) for selective screening, 48% of the participating population needed to be screened to find 80% (95% CI 78.4% to 81.0%) of Ct infections. The model with registry risk factors only (AUC 0.67, 95% CI 0.656 to 0.675) required 60% to be screened to find 78% (95% CI 76.6% to 79.4%) of Ct infections. CONCLUSIONS: A registry-based prediction model can facilitate selective Ct screening at population level, with further refinement at the individual level by including questionnaire risk factors. PMID- 26843402 TI - Hunting the genes in male-pattern alopecia: how important are they, how close are we and what will they tell us? AB - Androgenetic alopecia (AGA) is a highly heritable condition, and the most common form of hair loss in men. The phenotype is characterized by an androgen dependent, progressive loss of hair from the scalp, which may commence during puberty. Up to 80% of European men experience some degree of androgen-dependent hair loss during their lifetime. Current treatment options for AGA have limited efficacy, and improved understanding of the underlying biological causes is required to facilitate novel therapeutic approaches. To date, molecular genetic studies have implicated 12 genomic regions in AGA and identified a number of candidate genes. The latter include those encoding the androgen receptor (AR), the histone deacetylases (HDAC) 4 and 9, and the WNT molecule WNT10A. However, the majority of contributing genetic risk factors still await identification. This review describes the current status of AGA genetic research. We discuss the strength of the genetic approach and anticipated developments in the field, and how these will facilitate the systematic unravelling of AGA pathobiology, a process which may lead to the identification of new therapeutic targets. PMID- 26843403 TI - Identification of Biochemical Pathways Associated with Lead Tolerance and Detoxification in Chrysopogon zizanioides L. Nash (Vetiver) by Metabolic Profiling. AB - Lead (Pb) is a major urban pollutant, due to deteriorating lead-based paint in houses built before 1978. Phytoremediation is an inexpensive and effective technique for remediation of Pb-contaminated homes. Vetiver (Chrysopogon zizanioides), a noninvasive, fast-growing grass with high biomass, can tolerate and accumulate large quantities of Pb in its tissues. Lead is known to induce phytochelatins and antioxidative enzymes in vetiver; however, the overall impact of Pb stress on metabolic pathways of vetiver is unknown. In the current study, vetiver plants were treated with different concentrations of Pb in a hydroponic setup. Metabolites were extracted and analyzed using LC/MS/MS. Multivariate analysis of metabolites in both root and shoot tissue showed tremendous induction in key metabolic pathways including sugar metabolism, amino acid metabolism, and an increase in production of osmoprotectants, such as betaine and polyols, and metal-chelating organic acids. The data obtained provide a comprehensive insight into the overall stress response mechanisms in vetiver. PMID- 26843404 TI - Von Willebrand factor for menorrhagia: a survey and literature review. AB - BACKGROUND: von Willebrand disease (VWD) is the most common congenital bleeding disorder. In women, menorrhagia is the most common bleeding symptom, and is disabling with iron deficiency anaemia, high health cost and poor quality of life. Current hormonal and non-hormonal therapies are limited by ineffectiveness and intolerance. Few data exist regarding von Willebrand factor (VWF), typically prescribed when other treatments fail. The lack of effective therapy for menorrhagia remains the greatest unmet healthcare need in women with VWD. Better therapies are needed to treat women with menorrhagia. METHODS: We conducted a survey of US haemophilia treatment centres (HTCs) and a literature review using medical subject heading (MeSH) search terms 'von Willebrand factor,' 'menorrhagia' and 'von Willebrand disease' to assess the use of VWF in menorrhagia. Analysis was by descriptive statistics. RESULTS: Of 83 surveys distributed to HTC MDs, 20 (24.1%) provided sufficient data for analysis. Of 1321 women with VWD seen during 2011-2014, 816 (61.8%) had menorrhagia, for which combined oral contraceptives, tranexamic acid and desmopressin were the most common first-line therapies for menorrhagia, whereas VWF was third-line therapy reported in 13 women (1.6%). Together with data from 88 women from six published studies, VWF safely reduced menorrhagia in 101 women at a dose of 33-100 IU kg( 1) on day 1-6 of menstrual cycle. CONCLUSIONS: This represents the largest VWD menorrhagia treatment experience to date. VWF safely and effectively reduces menorrhagia in women with VWD. A prospective clinical trial is planned to confirm these findings. PMID- 26843407 TI - Enterovirus 68 Infection--Association with Asthma. AB - A previously sporadic virus called enterovirus 68 (EV-D68) appears to have been associated with asthma-like illness with a predisposition for asthmatics after an outbreak that occurred in North America in 2014. Clinicians should be aware of the clinical associations with EV-D68 particularly its predilection with pre existing asthma or asthma-like illness as well as the potential association with acute flaccid myelitis. Further elucidation and development of diagnostic and treatments modalities are warranted to better understand and limit the potential public health impact of future outbreaks of EV-D68 infection. PMID- 26843408 TI - Ionic liquid as a mobile phase additive in high-performance liquid chromatography for the simultaneous determination of eleven fluorescent whitening agents in paper materials. AB - In the present study, 11 4,4'-diaminostilbene-2,2'-disulfonic acid based fluorescent whitening agents with different numbers of sulfonic acid groups were separated by using an ionic liquid as a mobile phase additive in high-performance liquid chromatography with fluorescence detection. The effects of ionic liquid concentration, pH of mobile phase B, and composition of mobile phase A on the separation of fluorescent whitening agents were systematically investigated. The ionic liquid tetrabutylammonium tetrafluoroborate is superior to tetrabutylammomnium bromide for the separation of the fluorescent whitening agents. The optimal separation conditions were an ionic liquid concentration at 8 mM and the pH of mobile phase B at 8.5 with methanol as mobile phase A. The established method exhibited low limits of detection (0.04-0.07 ng/mL) and wide linearity ranges (0.30-20 ng/mL) with high linear correlation coefficients from 0.9994 to 0.9998. The optimized procedure was applied to analyze target analytes in paper samples with satisfactory results. Eleven target analytes were quantified, and the recoveries of spiked paper samples were in the range of 85 105% with the relative standard deviations from 2.1 to 5.1%. The obtained results indicated that the method was efficient for detection of 11 fluorescent whitening agents. PMID- 26843405 TI - Immunotherapy for pancreatic cancer. AB - INTRODUCTION: Pancreatic cancer is among the most lethal malignancies resistant to conventional therapies. The vast majority of patients is diagnosed with advanced/metastatic disease and consequently has grim prognosis. Despite the available options with nab-paclitaxel and gemcitabine or 5 fluorouracil/leucovorin/oxaliplatin, chemotherapy offers a modest survival benefit. Targeted therapy in combination with chemotherapy has not shown significant improvement in treatment outcomes. The urgent need for new therapies has turned the spotlights on immunotherapy. Immunotherapy in pancreatic cancer recruits and activates T cells which recognize tumor-specific antigens. RESULTS: Preclinical models have demonstrated that chemotherapy or targeted therapy works synergistically with immunotherapy. A growing body of evidence has already been gathered regarding the efficacy of checkpoint inhibitors, vaccines, adoptive T cell therapy, monoclonal antibodies, and cytokines in patients with pancreatic cancer. CONCLUSIONS: Many ongoing trials are aiming to identify treatments which could combine efficacy with limited toxicity. In this article, we review the available data concerning multiple aspects of immunotherapy in pancreatic cancer. PMID- 26843406 TI - Cor a 14, Hazelnut-Specific IgE, and SPT as a Reliable Tool in Hazelnut Allergy Diagnosis in Eastern Mediterranean Children. AB - BACKGROUND: Improving the diagnostic efficacy of laboratory tests might reduce the need for oral food challenges and facilitate our daily practice. OBJECTIVE: We aimed to determine cutoff values and probability curves, as well as to investigate the role of component-resolved diagnosis in predicting clinical reactivity in children with hazelnut allergy and to evaluate the association with pollen sensitivity. METHODS: A total of 56 children with hazelnut allergy who underwent double-blind placebo-controlled food challenge and 8 children who experienced anaphylaxis after accidental hazelnut intake were included. Serum IgE levels to hazelnut extract, Cor a 1, Cor a 8, Cor a 9, Cor a 14, and Bet v 1 were measured with the ImmunoCAP system. Skin prick tests (SPT) with hazelnut, other implicated foods, and aeroallergens were performed. RESULTS: The optimal cutoff levels for hazelnut sIgE and SPT wheal diameter that predicted clinical reactivity with the highest sensitivity and specificity were 3.15 kU/L and 7.5 mm, respectively. Among the components, only Cor a 14 discriminated between reactive and nonreactive children. The area under curve (AUC) at the optimal cutoff point of 0.63 kU/L for Cor a 14 (0.936) was higher than the AUC of hazelnut sIgE (0.818) and SPT wheal diameter (0.803). For the first time, a 95% probability for clinical reactivity was estimated for SPT wheal diameter, IgE to hazelnut extract, and to Cor a 14 at 12 mm, 10.2 kU/L, and 1.0 kU/L, respectively. CONCLUSION: Cor a 14 was found to be a useful and reliable tool for predicting clinical reactivity in children with hazelnut allergy in the Eastern Mediterranean area. PMID- 26843409 TI - Dissecting ion-specific from electrostatic salt effects on amyloid fibrillation: A case study of insulin. AB - Diseases like Alzheimer, type II diabetes mellitus, and others go back to fibril formation of partially unfolded proteins. The impact of sodium, potassium, choline, guanidinium, and 1-ethyl-3-methylimidazolium chloride on the fibrillation kinetics of insulin in an acid-denaturing solvent environment is studied by fluorescence spectroscopy using thioflavin T as a fibril-specific stain. The fibrillation kinetics reveal a sigmoidal behavior, characterized by the lag time taulag and the maximum elongation rate k of the fibrils. Up to ionic strengths of about 70 mM, the elongation rate increases with salt concentration. This increase is nonspecific with regard to the salts. Below ionic strengths of ~50 mM, it can be explained by a Debye-Huckel type model, indicating a dominant role of Coulomb interactions between the charged reactants and products screened by the ionic environment. At higher ionic strength, the elongation rates pass maxima, followed by a Hofmeister type ion-specific decrease. There is a correlation between the lag time taulag and the inverse elongation rate k, which can be described by a power law of the form taulag ? atau(alpha) with a sublinear exponent alpha ? 1/2. PMID- 26843410 TI - App Review Series: RadioGraphics. PMID- 26843411 TI - Archegonous Cystic Odontoma Is Not Necessarily Primordial. PMID- 26843413 TI - Patient safety and rocket science. PMID- 26843412 TI - Crew resource management training in the intensive care unit. A multisite controlled before-after study. AB - INTRODUCTION: There is a growing awareness today that adverse events in the intensive care unit (ICU) are more often caused by problems related to non technical skills than by a lack of technical, or clinical, expertise. Team training, such as crew resource management (CRM), aims to improve these non technical skills. The present study evaluated the effectiveness of CRM in the ICU. METHODS: Six ICUs participated in a paired controlled trial, with one pretest and two post-test measurements (after 3 and 12 months). Three ICUs received CRM training and were compared with a matched control unit. The 2-day classroom-based training was delivered to multidisciplinary groups (ie, ICU physicians, nurses, managers). All levels of Kirkpatrick's evaluation framework were assessed using a mixed method design, including questionnaires, observations and routinely administered patient outcome data. RESULTS: Level I-reaction: participants were very positive directly after the training. Level II-learning: attitudes towards behaviour aimed at optimising situational awareness were relatively high at baseline and remained stable. Level III-behaviour: self reported behaviour aimed at optimising situational awareness improved in the intervention group. No changes were found in observed explicit professional oral communication. Level IV-organisation: patient outcomes were unaffected. Error management culture and job satisfaction improved in the intervention group. Patient safety culture improved in both control and intervention units. CONCLUSIONS: We can conclude that CRM, as delivered in the present study, does not change behaviour or patient outcomes by itself, yet changes how participants think about errors and risks. This indicates that CRM requires a combination with other initiatives in order to improve clinical outcomes. PMID- 26843414 TI - What doctors think would make NHS 111 safer. PMID- 26843415 TI - Does solitary- and organ-confined metastasectomy really improve survival in advanced urologic malignancies? AB - The role of metastasectomy on survival in advanced/urologic malignancies still remains unclear. Renal cell carcinoma (RCC) is the most common solid tumor within the kidney. 25-30 % of patients have metastases at manifestation. Urothelial carcinoma (UC) consists of bladder carcinoma, upper urinary tract urothelial cell carcinoma and urethral carcinoma. Bladder cancer is the ninth most common cancer worldwide. Half of patients with muscle invasive bladder cancer have lymph node or distant metastases. In metastatic disease first-line treatment is multi-agent platinum-based systemic chemotherapy. Testicular cancer is the most common cancer in men between the age of 15 and 35. Testicular tumors represent excellent oncologic outcomes. Prostate cancer is the most common solid tumor in Europe. Surgical resection of metastases can be considered as a treatment choice in advanced/metastatic urologic malignancies to improve survival rates, particularly in RCC and UC. Metastasectomy can be suggested in conjunction with effective chemotherapy if complete resection is possible. Solitary metastasectomy can represent better survival rates compared to multiple metastasectomy even if multiple metastases confined to single organ. Site of metastases is one of the main determinants of successful metastasectomy such as lung metastasectomy in urothelial cell carcinoma and liver metastasectomy in RCC may lead to better oncologic outcomes. Due to the lack of the relevant data it is not possible to make an evidence-based recommendation on the role of metastasectomy for solitary /organ-confined metastases of prostate cancer, testicular cancer and penile cancer. PMID- 26843416 TI - Spinal glycine transporter-1 inhibition influences the micturition reflex in urethane-anesthetized rats. AB - PURPOSE: Glycine is an inhibitory neurotransmitter in the central nervous system. So far, two types of glycine transporters (GlyTs), GlyT-1 and GlyT-2, have been cloned. The aim of this study is to investigate the effects of a selective GlyT-1 inhibitor that can increase endogenous glycine concentration on the micturition reflex in urethane-anesthetized rats. METHODS: Continuous cystometrograms (0.04 ml/min) were performed in female Sprague-Dawley rats (232-265 g) under urethane anesthesia. After stable micturition cycles were established, ALX5407, a selective GlyT-1 inhibitor, was administered intrathecally or intracerebroventricularly to evaluate changes in bladder activity. Cystometric parameters were recorded and compared before and after drug administration. RESULTS: Intrathecal administration of ALX5407 (1, 3, 10 and 30 MUg) increased intercontraction intervals at doses of 3 MUg or higher in a dose-dependent fashion. Intrathecal administration of ALX5407 (1, 3, 10 and 30 MUg) also increased pressure threshold at doses of 3 MUg or higher in a dose-dependent fashion. However, when ALX5407 (1, 3, 10 and 30 MUg) was administered intracerebroventricularly, there were no significant changes in intercontraction intervals, pressure threshold, maximum voiding pressure or baseline pressure or post-void residual urine volume at any doses tested. CONCLUSION: The results of our study indicate that GlyT-1 plays an important role in the modulation of micturition. Furthermore, these findings indicate that in urethane-anesthetized rats suppression of GlyT-1 can inhibit the micturition reflex at the spinal cord level. Thus, GlyT-1 could be a potential target for the treatment of bladder dysfunction such as overactive bladder. PMID- 26843417 TI - Atomic Force Microscopy Study of Atherosclerosis Progression in Arterial Walls. AB - Cardiovascular disease remains the leading cause of mortality worldwide. Here we suggest a novel approach for tracking atherosclerosis progression based on the use of atomic force microscopy (AFM). Using AFM, we studied cross-sections of coronary arteries with the following types of lesions: Type II-thickened intima; Type III-thickened intima with a lipid streak; Type IV-fibrotic layer over a lipid core; Type Va-unstable fibrotic layer over a lipid core; Type Vc-very thick fibrotic layer. AFM imaging revealed that the fibrotic layer of an atherosclerotic plaque is represented by a basket-weave network of collagen fibers and a subscale network of fibrils that become looser with atherosclerosis progression. In an unstable plaque (Type Va), packing of the collagen fibers and fibrils becomes even less uniform than that at the previous stages, while a stable fibrotic plaque (Vc) has significantly tighter packing. Such alterations of the collagen network morphology apparently, led to deterioration of the Type Va plaque mechanical properties, that, in turn, resulted in its instability and propensity to rupture. Thus, AFM may serve as a useful tool for tracking atherosclerosis progression in the arterial wall tissue. PMID- 26843418 TI - Attention: Guiding the way. PMID- 26843419 TI - Advantages of being diligent: lessons learnt from umbilical venous catheterisation in neonates. AB - Umbilical venous catheters (UVCs) are commonly used in neonatal units. Abdominal radiograph, taken soon after the insertion, is used to confirm the correct placement of the catheter. However, as demonstrated by our case series, complacency when an initial UVC is normally positioned can lead to detecting UVC related complications very late. We describe cases of three neonates where, despite the initial UVC being confirmed to be well positioned, the patients developed life-threatening complications, including liver haematoma, left atrial thrombus and pericardial effusion causing cardiac tamponade. The routine use of point of care echocardiography helped in the early diagnosis of these complications. We suggest repeated echocardiographic screening at regular intervals in all newborn babies requiring UVCs, to ensure that the catheter is maintained in the proper position and for the early detection of catheter-related complications. PMID- 26843420 TI - Massive right pleural effusion leading to cardiac tamponade in absence of pericardial effusion: a rare presentation. PMID- 26843421 TI - Views from health professionals on accessing rehabilitation for people with dementia following a hip fracture. AB - The literature reports that rehabilitation for elderly patients with mild-to moderate dementia who have a hip fracture improves functional outcomes. However, access to rehabilitation may be difficult due to misconceptions about the ability of these patients to engage in and benefit from rehabilitation. Additionally, people who are admitted from residential care may not have the same options for rehabilitation as those admitted from home. This study sought to understand from expert clinicians how and why decisions are made to accept a person with dementia post-fracture for rehabilitation. In this Australian-based qualitative study, 12 health professionals across a state and territory were interviewed. These clinicians were the primary decision makers in accepting or rejecting elderly patients with dementia post-fracture into rehabilitation. Three key themes emerged from the data: criteria for accessing rehabilitation, what works well and challenges to rehabilitation. The participants were unanimous in the view that access to rehabilitation should be based on the ability of the patient to engage in a rehabilitation programme and not assessed solely on cognition. In terms of clinical care, a coherent rehabilitation pathway with integration of geriatric and ortho-geriatric services was reported as ideal. Challenges remain, importantly, the perception of some health care staff that people with dementia have limited capability to benefit from rehabilitation. Rehabilitation for this growing group of patients requires multiple resources, including skilled practitioners, integrated clinical systems and staff education regarding the capabilities of people with dementia. Future research in this area with patients with moderate-to-severe dementia in residential care is warranted. PMID- 26843422 TI - Reciprocal regulation of autism-related genes MeCP2 and PTEN via microRNAs. AB - MeCP2 encodes a methyl-CpG-binding protein that plays a critical role in repressing gene expression, mutations of which lead to Rett syndrome and autism. PTEN is a critical tumor suppressor gene that is frequently mutated in human cancers and autism spectrum disorders. Various studies have shown that both MeCP2 and PTEN proteins play important roles in brain development. Here we find that MeCP2 and PTEN reciprocally regulate expression of each other via microRNAs. Knockdown of MeCP2 leads to upregulation of microRNA-137, which in turn represses expression of PTEN, thus PTEN would be down-regulated when MeCP2 is knockdown. Furthermore, we find that deletion of PTEN leads to phosphorylation of Serine 133 of CREB, then increases the expression of microRNA-132. miR-132 inhibits the expression of MeCP2 by targeting on the 3'UTR of MeCP2 mRNA. Our work shows that two critical disorders-related gene MeCP2 and PTEN reciprocally regulate expression of each other by distinct mechanisms, suggesting that rare mutations in various disorders may lead to dysregulation of other critical genes and yield unexpected consequences. PMID- 26843423 TI - Negative outcomes evoke cyclic irrational decisions in Rock, Paper, Scissors. AB - Rock, Paper, Scissors (RPS) represents a unique gaming space in which the predictions of human rational decision-making can be compared with actual performance. Playing a computerized opponent adopting a mixed-strategy equilibrium, participants revealed a non-significant tendency to over-select Rock. Further violations of rational decision-making were observed using an inter trial analysis where participants were more likely to switch their item selection at trial n + 1 following a loss or draw at trial n, revealing the strategic vulnerability of individuals following the experience of negative rather than positive outcome. Unique switch strategies related to each of these trial n outcomes were also identified: after losing participants were more likely to 'downgrade' their item (e.g., Rock followed by Scissors) but after drawing participants were more likely to 'upgrade' their item (e.g., Rock followed by Paper). Further repetition analysis revealed that participants were more likely to continue their specific cyclic item change strategy into trial n + 2. The data reveal the strategic vulnerability of individuals following the experience of negative rather than positive outcome, the tensions between behavioural and cognitive influences on decision making, and underline the dangers of increased behavioural predictability in other recursive, non-cooperative environments such as economics and politics. PMID- 26843425 TI - Oral anticoagulation, stroke and thromboembolism in patients with atrial fibrillation and valve bioprosthesis. The Loire Valley Atrial Fibrillation Project. AB - Vitamin K antagonists are currently recommended in patients with 'valvular' atrial fibrillation (AF), e. g. those having mitral stenosis or artificial heart valves. We compared thromboembolic risk in patients with 'non valvular' AF and in those with AF and biological valve replacement (valve bioprosthesis). Among 8962 AF patients seen between 2000 and 2010, a diagnosis of 'non-valvular AF' was found in 8053 (94 %). Among patients with 'valvular' AF, 549 (6 %) had a biological prosthesis. The patients with bioprosthesis were older and had a higher CHA2DS2-VASc score than those with non valvular AF. After a follow-up of 876 +/- 1048 days (median 400 days, interquartile range 12-1483), the occurrence of thromboembolic events was similar in AF patients with bioprosthesis compared to those with 'non valvular' AF (hazard ratio [HR] 1.10 95 % confidence interval [CI] 0.83-1.45, p=0.52, adjusted HR 0.93, 95 %CI 0.68-1.25, p=0.61). Factors independently associated with increased risk of stroke/TE events were older age (HR 1.25, 95 %CI 1.16-1.34 per 10-year increase, p< 0.0001) and higher CHA2DS2 VASc score (HR 1.35, 95 %CI 1.24-1.46, p< 0.0001) whilst female gender (HR 0.75, 95 %CI 0.62-0.90, p=0.002), use of vitamin K antagonist (HR 0.83, 95 %CI 0.71 0.98, p=0.03) were independently associated with a lower risk of stroke/TE. Neither the presence of bioprosthesis nor the location of bioprosthesis was independent predictor for TE events. In conclusion, AF patients with bioprosthesis had a non-significantly higher risk of stroke/TE events compared to patients with non-valvular AF. Second, the CHA2DS2-VASc score was independently associated with an increased risk of TE events, and was a valuable determinant of TE risk both in AF patients with non-valvular AF as well as those with bioprosthesis, whether treated or not treated with OAC. PMID- 26843424 TI - Paired box 5 is a frequently methylated lung cancer tumour suppressor gene interfering beta-catenin signalling and GADD45G expression. AB - Recent studies suggest that paired box 5 (PAX5) is down-regulated in multiple tumours through its promoter methylation. However, the role of PAX5 in non-small cell lung cancer (NSCLC) pathogenesis remains unclear. The aim of this study is to examine PAX5 expression, its methylation status, biological functions and related molecular mechanism in NSCLC. We found that PAX5 was widely expressed in normal adult tissues but silenced or down-regulated in 88% (7/8) of NSCLC cell lines. PAX5 expression level was significantly lower in NSCLC than that in adjacent non-cancerous tissues (P = 0.0201). PAX5 down-regulation was closely associated with its promoter hypermethylation status and PAX5 expression could be restored by demethylation treatment. Frequent PAX5 promoter methylation in primary tumours (70%) was correlated with lung tumour histological types (P = 0.006). Ectopic expression of PAX5 in silenced lung cancer cell lines (A549 and H1975) inhibited their colony formation and cell viability, arrested cell cycle at G2 phase and suppressed cell migration/invasion as well as tumorigenicity in nude mice. Restoration of PAX5 expression resulted in the down-regulation of beta catenin and up-regulation of tissue inhibitors of metalloproteinase 2, GADD45G in lung tumour cells. In summary, PAX5 was found to be an epigenetically inactivated tumour suppressor that inhibits NSCLC cell proliferation and metastasis, through down-regulating the beta-catenin pathway and up-regulating GADD45G expression. PMID- 26843426 TI - PON-mt-tRNA: a multifactorial probability-based method for classification of mitochondrial tRNA variations. AB - Transfer RNAs (tRNAs) are essential for encoding the transcribed genetic information from DNA into proteins. Variations in the human tRNAs are involved in diverse clinical phenotypes. Interestingly, all pathogenic variations in tRNAs are located in mitochondrial tRNAs (mt-tRNAs). Therefore, it is crucial to identify pathogenic variations in mt-tRNAs for disease diagnosis and proper treatment. We collected mt-tRNA variations using a classification based on evidence from several sources and used the data to develop a multifactorial probability-based prediction method, PON-mt-tRNA, for classification of mt-tRNA single nucleotide substitutions. We integrated a machine learning-based predictor and an evidence-based likelihood ratio for pathogenicity using evidence of segregation, biochemistry and histochemistry to predict the posterior probability of pathogenicity of variants. The accuracy and Matthews correlation coefficient (MCC) of PON-mt-tRNA are 1.00 and 0.99, respectively. In the absence of evidence from segregation, biochemistry and histochemistry, PON-mt-tRNA classifies variations based on the machine learning method with an accuracy and MCC of 0.69 and 0.39, respectively. We classified all possible single nucleotide substitutions in all human mt-tRNAs using PON-mt-tRNA. The variations in the loops are more often tolerated compared to the variations in stems. The anticodon loop contains comparatively more predicted pathogenic variations than the other loops. PON-mt-tRNA is available at http://structure.bmc.lu.se/PON-mt-tRNA/. PMID- 26843427 TI - Transcription profile of Escherichia coli: genomic SELEX search for regulatory targets of transcription factors. AB - Bacterial genomes are transcribed by DNA-dependent RNA polymerase (RNAP), which achieves gene selectivity through interaction with sigma factors that recognize promoters, and transcription factors (TFs) that control the activity and specificity of RNAP holoenzyme. To understand the molecular mechanisms of transcriptional regulation, the identification of regulatory targets is needed for all these factors. We then performed genomic SELEX screenings of targets under the control of each sigma factor and each TF. Here we describe the assembly of 156 SELEX patterns of a total of 116 TFs performed in the presence and absence of effector ligands. The results reveal several novel concepts: (i) each TF regulates more targets than hitherto recognized; (ii) each promoter is regulated by more TFs than hitherto recognized; and (iii) the binding sites of some TFs are located within operons and even inside open reading frames. The binding sites of a set of global regulators, including cAMP receptor protein, LeuO and Lrp, overlap with those of the silencer H-NS, suggesting that certain global regulators play an anti-silencing role. To facilitate sharing of these accumulated SELEX datasets with the research community, we compiled a database, 'Transcription Profile of Escherichia coli' (www.shigen.nig.ac.jp/ecoli/tec/). PMID- 26843429 TI - RNA cleavage products generated by antisense oligonucleotides and siRNAs are processed by the RNA surveillance machinery. AB - DNA-based antisense oligonucleotides (ASOs) elicit cleavage of the targeted RNA by the endoribonuclease RNase H1, whereas siRNAs mediate cleavage through the RNAi pathway. To determine the fates of the cleaved RNA in cells, we lowered the levels of the factors involved in RNA surveillance prior to treating cells with ASOs or siRNA and analyzed cleavage products by RACE. The cytoplasmic 5' to 3' exoribonuclease XRN1 was responsible for the degradation of the downstream cleavage products generated by ASOs or siRNA targeting mRNAs. In contrast, downstream cleavage products generated by ASOs targeting nuclear long non-coding RNA Malat 1 and pre-mRNA were degraded by nuclear XRN2. The downstream cleavage products did not appear to be degraded in the 3' to 5' direction as the majority of these products contained intact poly(A) tails and were bound by the poly(A) binding protein. The upstream cleavage products of Malat1 were degraded in the 3' to 5' direction by the exosome complex containing the nuclear exoribonuclease Dis3. The exosome complex containing Dis3 or cytoplasmic Dis3L1 degraded mRNA upstream cleavage products, which were not bound by the 5'-cap binding complex and, consequently, were susceptible to degradation in the 5' to 3' direction by the XRN exoribonucleases. PMID- 26843428 TI - The downregulation of the RNA-binding protein Staufen2 in response to DNA damage promotes apoptosis. AB - Staufen2 (Stau2) is an RNA-binding protein involved in cell fate decision by controlling several facets of mRNA processing including localization, splicing, translation and stability. Herein we report that exposure to DNA-damaging agents that generate replicative stress such as camptothecin (CPT), 5-fluoro-uracil (5FU) and ultraviolet radiation (UVC) causes downregulation of Stau2 in HCT116 colorectal cancer cells. In contrast, other agents such as doxorubicin and ionizing radiation had no effect on Stau2 expression. Consistently, Stau2 expression is regulated by the ataxia telangiectasia and Rad3-related (ATR) signaling pathway but not by the DNA-PK or ataxia telangiectasia mutated/checkpoint kinase 2 pathways. Stau2 downregulation is initiated at the level of transcription, independently of apoptosis induction. Promoter analysis identified a short 198 bp region which is necessary and sufficient for both basal and CPT-regulated Stau2 expression. The E2F1 transcription factor regulates Stau2 in untreated cells, an effect that is abolished by CPT treatment due to E2F1 displacement from the promoter. Strikingly, Stau2 downregulation enhances levels of DNA damage and promotes apoptosis in CPT-treated cells. Taken together our results suggest that Stau2 is an anti-apoptotic protein that could be involved in DNA replication and/or maintenance of genome integrity and that its expression is regulated by E2F1 via the ATR signaling pathway. PMID- 26843430 TI - An interplay of the base excision repair and mismatch repair pathways in active DNA demethylation. AB - Active DNA demethylation (ADDM) in mammals occurs via hydroxylation of 5 methylcytosine (5mC) by TET and/or deamination by AID/APOBEC family enzymes. The resulting 5mC derivatives are removed through the base excision repair (BER) pathway. At present, it is unclear how the cell manages to eliminate closely spaced 5mC residues whilst avoiding generation of toxic BER intermediates and whether alternative DNA repair pathways participate in ADDM. It has been shown that non-canonical DNA mismatch repair (ncMMR) can remove both alkylated and oxidized nucleotides from DNA. Here, a phagemid DNA containing oxidative base lesions and methylated sites are used to examine the involvement of various DNA repair pathways in ADDM in murine and human cell-free extracts. We demonstrate that, in addition to short-patch BER, 5-hydroxymethyluracil and uracil mispaired with guanine can be processed by ncMMR and long-patch BER with concomitant removal of distant 5mC residues. Furthermore, the presence of multiple mispairs in the same MMR nick/mismatch recognition region together with BER-mediated nick formation promotes proficient ncMMR resulting in the reactivation of an epigenetically silenced reporter gene in murine cells. These findings suggest cooperation between BER and ncMMR in the removal of multiple mismatches that might occur in mammalian cells during ADDM. PMID- 26843431 TI - Nanotechnology applications in thoracic surgery. AB - Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent nanotechnological advances show particular promise to improve outcomes for thoracic surgical patients. A variety of nanotechnologies are described that offer possible solutions to existing challenges encountered in the detection, diagnosis and treatment of lung cancer. Nanotechnology-based imaging platforms have the ability to improve the surgical care of patients with thoracic malignancies through technological advances in intraoperative tumour localization, lymph node mapping and accuracy of tumour resection. Moreover, nanotechnology is poised to revolutionize adjuvant lung cancer therapy. Common chemotherapeutic drugs, such as paclitaxel, docetaxel and doxorubicin, are being formulated using various nanotechnologies to improve drug delivery, whereas nanoparticle (NP)-based imaging technologies can monitor the tumour microenvironment and facilitate molecularly targeted lung cancer therapy. Although early nanotechnology-based delivery systems show promise, the next frontier in lung cancer therapy is the development of 'theranostic' multifunctional NPs capable of integrating diagnosis, drug monitoring, tumour targeting and controlled drug release into various unifying platforms. This article provides an overview of key existing and emerging nanotechnology platforms that may find clinical application in thoracic surgery in the near future. PMID- 26843432 TI - Myocardial function after polarizing versus depolarizing cardiac arrest with blood cardioplegia in a porcine model of cardiopulmonary bypass. AB - OBJECTIVES: Potassium-based depolarizing St Thomas' Hospital cardioplegic solution No 2 administered as intermittent, oxygenated blood is considered as a gold standard for myocardial protection during cardiac surgery. However, the alternative concept of polarizing arrest may have beneficial protective effects. We hypothesize that polarized arrest with esmolol/adenosine/magnesium (St Thomas' Hospital Polarizing cardioplegic solution) in cold, intermittent oxygenated blood offers comparable myocardial protection in a clinically relevant animal model. METHODS: Twenty anaesthetized young pigs, 42 +/- 2 (standard deviation) kg on standardized tepid cardiopulmonary bypass (CPB) were randomized (10 per group) to depolarizing or polarizing cardiac arrest for 60 min with cardioplegia administered in the aortic root every 20 min as freshly mixed cold, intermittent, oxygenated blood. Global and local baseline and postoperative cardiac function 60, 120 and 180 min after myocardial reperfusion was evaluated with pressure conductance catheter and strain by Tissue Doppler Imaging. Regional tissue blood flow, cleaved caspase-3 activity, GRK2 phosphorylation and mitochondrial function and ultrastructure were evaluated in myocardial tissue samples. RESULTS: Left ventricular function and general haemodynamics did not differ between groups before CPB. Cardiac asystole was obtained and maintained during aortic cross clamping. Compared with baseline, heart rate was increased and left ventricular end-systolic and end-diastolic pressures decreased in both groups after weaning. Cardiac index, systolic pressure and radial peak systolic strain did not differ between groups. Contractility, evaluated as dP/dtmax, gradually increased from 120 to 180 min after declamping in animals with polarizing cardioplegia and was significantly higher, 1871 +/- 160 (standard error) mmHg/s, compared with standard potassium-based cardioplegic arrest, 1351 +/- 70 mmHg/s, after 180 min of reperfusion (P = 0.008). Radial peak ejection strain rate increased and the load-independent variable preload recruitable stroke work was increased with polarizing cardioplegia after 180 min, 64 +/- 3 vs 54 +/- 2 mmHg (P = 0.018), indicating better preserved left ventricular contractility with polarizing cardioplegia. Phosphorylation of GRK2 in myocardial tissue did not differ between groups. Fractional cytoplasmic volume in myocytes was reduced in hearts arrested with polarizing cardioplegia, indicating reduction of cytoplasmic oedema. CONCLUSIONS: Polarizing oxygenated blood cardioplegia with esmolol/adenosine/magnesium offers comparable myocardial protection and improves contractility compared with the standard potassium-based depolarizing blood cardioplegia. PMID- 26843436 TI - Selectivity of CO2 via pore space partition in zeolitic boron imidazolate frameworks. AB - Reported here is a versatile method capable of generating pore space partition in zeolitic boron imidazolate frameworks (BIFs), which is based on the coexistence of presynthesized boron imidazolate complexes and charge balancing carboxylate ligands. Using this method, boron imidazolate complexes are used to form zeolitic nets, while the carboxylate serves to partition large channel spaces into multiple domains. The generality of this method is shown by two distinct boron imidazolate frameworks mimicking GIS (BIF-41) and ABW (BIF-42) zeotype topologies. BIF-41 shows high selectivity sorption of CO2 over N2. PMID- 26843434 TI - A semi-automatic computer-aided method for surgical template design. AB - This paper presents a generalized integrated framework of semi-automatic surgical template design. Several algorithms were implemented including the mesh segmentation, offset surface generation, collision detection, ruled surface generation, etc., and a special software named TemDesigner was developed. With a simple user interface, a customized template can be semi- automatically designed according to the preoperative plan. Firstly, mesh segmentation with signed scalar of vertex is utilized to partition the inner surface from the input surface mesh based on the indicated point loop. Then, the offset surface of the inner surface is obtained through contouring the distance field of the inner surface, and segmented to generate the outer surface. Ruled surface is employed to connect inner and outer surfaces. Finally, drilling tubes are generated according to the preoperative plan through collision detection and merging. It has been applied to the template design for various kinds of surgeries, including oral implantology, cervical pedicle screw insertion, iliosacral screw insertion and osteotomy, demonstrating the efficiency, functionality and generality of our method. PMID- 26843433 TI - Standardized Uptake Values from PET/MRI in Metastatic Breast Cancer: An Organ based Comparison With PET/CT. AB - Quantitative standardized uptake values (SUVs) from fluorine-18 (18F) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) are commonly used to evaluate the extent of disease and response to treatment in breast cancer patients. Recently, PET/magnetic resonance imaging (MRI) has been shown to qualitatively detect metastases from various primary cancers with similar sensitivity to PET/CT. However, quantitative validation of PET/MRI requires assessing the reliability of SUVs from MR attenuation correction (MRAC) relative to CT attenuation correction (CTAC). The purpose of this retrospective study was to assess the utility of PET/MRI-derived SUVs in breast cancer patients by testing the hypothesis that SUVs derived from MRAC correlate well with those from CTAC. Between August 2012 and May 2013, 35 breast cancer patients (age 37-78 years, 1 man) underwent clinical 18F-FDG PET/CT followed by PET/MRI. One hundred seventy metastases were seen in 21 of 35 patients; metastases to bone in 16 patients, to liver in seven patients, and to nonaxillary lymph nodes in eight patients were sufficient for statistical analysis on an organ-specific per patient basis. SUVs in the most FDG-avid metastasis per organ per patient from PET/CT and PET/MRI were measured and compared using Pearson's correlations. Correlations between CTAC- and MRAC-derived SUVmax and SUVmean in 31 metastases to bone, liver, and nonaxillary lymph nodes were strong overall (rho = 0.80, 0.81). SUVmax and SUVmean correlations were also strong on an organ specific basis in 16 bone metastases (rho = 0.76, 0.74), seven liver metastases (rho = 0.85, 0.83), and eight nonaxillary lymph node metastases (rho = 0.95, 0.91). These strong organ-specific correlations between SUVs from PET/CT and PET/MRI in breast cancer metastases support the use of SUVs from PET/MRI for quantitation of 18F-FDG activity. PMID- 26843435 TI - Massive and massless Dirac fermions in Pb1-xSnxTe topological crystalline insulator probed by magneto-optical absorption. AB - Dirac fermions in condensed matter physics hold great promise for novel fundamental physics, quantum devices and data storage applications. IV-VI semiconductors, in the inverted regime, have been recently shown to exhibit massless topological surface Dirac fermions protected by crystalline symmetry, as well as massive bulk Dirac fermions. Under a strong magnetic field (B), both surface and bulk states are quantized into Landau levels that disperse as B(1/2), and are thus difficult to distinguish. In this work, magneto-optical absorption is used to probe the Landau levels of high mobility Bi-doped Pb0.54Sn0.46Te topological crystalline insulator (111)-oriented films. The high mobility achieved in these thin film structures allows us to probe and distinguish the Landau levels of both surface and bulk Dirac fermions and extract valuable quantitative information about their physical properties. This work paves the way for future magnetooptical and electronic transport experiments aimed at manipulating the band topology of such materials. PMID- 26843437 TI - A ruthenium water oxidation catalyst based on a carboxamide ligand. AB - Herein is presented a single-site Ru complex bearing a carboxamide-based ligand that efficiently manages to carry out the four-electron oxidation of H2O. The incorporation of the negatively charged ligand framework significantly lowered the redox potentials of the Ru complex, allowing H2O oxidation to be driven by the mild oxidant [Ru(bpy)3](3+). This work highlights that the inclusion of amide moieties into metal complexes thus offers access to highly active H2O oxidation catalysts. PMID- 26843438 TI - Does microscopically involved margin increase disease recurrence after curative surgery in papillary thyroid carcinoma? AB - BACKGROUND: The prognostic significance of microscopically involved margin in papillary thyroid carcinoma (PTC) following curative surgery remains unclear. We aimed to evaluate the impact of an involved margin and its location (anterior vs. posterior) on disease recurrence. METHODS: Of the 638 eligible patients, 538 (85.9%) did not have an involved margin (group I) while 100 (14.1%) did (group II). The latter group was further classified according to its location relative to the surface of the thyroid gland (anterior or posterior). A multivariate analysis was conducted to identify independent factors for recurrence risk. RESULTS: After a mean of 130.1 +/- 93.5 months, 22 patients had disease recurrence. The 10-year disease-free survival (DFS) was significantly worse in group II (95.0% vs. 97.0%, P = 0.011). After adjusting other significant factors, involved margin was not an independent risk factor for disease recurrence (P = 0.358). Compared to a negative margin, an anterior involved margin did not pose increased recurrence risk (HR = 1.21, 95%CI = 0.93-500.00, P = 0.368), whereas a posterior involved margin had almost 23 times higher recurrence risk (HR = 22.95; 95%CI = 4.33-121.70, P < 0.001). CONCLUSIONS: Overall, a microscopically involved margin was not an independent factor for DFS. However, although an anterior involved margin itself did not increase disease recurrence, a posterior involved margin did. J. Surg. Oncol. 2016;113:635-639. (c) 2016 Wiley Periodicals, Inc. PMID- 26843439 TI - The synthesis of Ni(II) and Al(III) 10-azacorroles through coordination-induced cyclisation involving 1,2-migration. AB - We have synthesized Ni(II) and Al(III) 10-azacorroles through coordination induced cyclisation of nitrogen-bridged bisdipyrrins. Al(III) 10-azacorrole displayed contrasting optoelectronic behaviours from Ni(II) 10-azacorrole, underlining the different electronic effects of the azacorrole ligand from the porphyrin. PMID- 26843441 TI - In vitro wear of flowable resin composite for posterior restorations. AB - The purpose of this study was to examine three- and two-body wear values of flowable resin composites for posterior restorations, using a mechanical loading device. The cavities prepared on flattened extracted molars were restored with flowable resin composites (Clearfil Majesty LV: MLV, Estelite Flow Quick: EFQ, Beautifil Flow Plus F00: BFP, and MI Fill: MIF) using accompanying adhesive systems. A universal resin composite (Clearfil Majesty) was used as a control. The specimens were subjected to in vitro three- and two-body wear testing. MLV showed high wear value (three-body: 14.69 um, two-body: 0.268 mm(3)) compared with other materials tested in both three- and two-body wear tests. BFP showed high three-body wear value (5.78 um), whereas low two-body wear value (0.008 mm(3)). MIF and EFQ showed equivalent wear values (MIF, three-body: 0.42 um, two body: 0.026 mm(3); EFQ, three-body: 1.15 um, two-body: 0.14 mm(3)) to that of the control in both wear tests. PMID- 26843442 TI - Effects of immersion disinfection of agar-alginate combined impressions on the surface properties of stone casts. AB - This study investigated the effects of disinfection of agar-alginate combined impressions on the surface properties of the resulting stone casts. Two brands of cartridge-form agar impression material and one alginate impression material were used. Agar-alginate combined impressions of smooth glass plates were prepared. The impressions were immersed in 0.55% ortho-phthalaldehyde solution or 0.5% sodium hypochlorite solution for 1, 3, 5 and 10 min. A stone cast made with an impression that had not been immersed was prepared as a control. The surface roughness (Ra) of the stone casts was measured, and the cast surfaces were observed by SEM. Immersion of agar-alginate combined impressions in 0.5% sodium hypochlorite solution for up to 10 min had no serious adverse effects on the surface properties of the stone casts. In contrast, even 1 min of immersion in 0.55% ortho-phthalaldehyde solution caused deterioration of the cast surface properties. PMID- 26843440 TI - VAMP7 regulates constitutive membrane incorporation of the cold-activated channel TRPM8. AB - The cation channel TRPM8 plays a central role in the somatosensory system, as a key sensor of innocuously cold temperatures and cooling agents. Although increased functional expression of TRPM8 has been implicated in various forms of pathological cold hypersensitivity, little is known about the cellular and molecular mechanisms that determine TRPM8 abundance at the plasma membrane. Here we demonstrate constitutive transport of TRPM8 towards the plasma membrane in atypical, non-acidic transport vesicles that contain lysosomal-associated membrane protein 1 (LAMP1), and provide evidence that vesicle-associated membrane protein 7 (VAMP7) mediates fusion of these vesicles with the plasma membrane. In line herewith, VAMP7-deficient mice exhibit reduced functional expression of TRPM8 in sensory neurons and concomitant deficits in cold avoidance and icilin induced cold hypersensitivity. Our results uncover a cellular pathway that controls functional plasma membrane incorporation of a temperature-sensitive TRP channel, and thus regulates thermosensitivity in vivo. PMID- 26843443 TI - Resveratrol modulates intestinal morphology and HSP70/90, NF-kappaB and EGF expression in the jejunal mucosa of black-boned chickens on exposure to circular heat stress. AB - The aim of this study was to investigate whether supplementation with resveratrol could alleviate intestinal injuries and to explore how resveratrol regulates heat shock protein (HSP)70, HSP90, nuclear factor kappa B (NF-kappaB) and epidermal growth factor (EGF) expression in the jejunal mucosa of black-boned chickens under circular heat stress. A total of 300 black-boned chicks of 42-d-old were randomly assigned to five treatment groups. The positive control chickens were kept in a normal-temperature (NT, 24 +/- 2 degrees C) chamber and fed with a basal diet. The other four groups were kept in a circular high-temperature (HT, 37 +/- 2 degrees C) chamber for 8 h and fed a basal diet supplemented with 0, 200, 400, or 600 mg per kg of resveratrol for 15 days. The results showed that the heat-stress responses damaged the villus structures of the jejunum and ileum, resulting in shortened intestinal villi, deepened crypts, and a reduced villus height to crypt depth (V/C) ratio and decreased the numbers of goblet cells and lymphocytes. Heat stress also caused increased mRNA and protein expression of HSP70, HSP90 and NF-kappaB, and reduced EGF in the jejunal mucosa. Dietary supplementation with 400 mg per kg of resveratrol improved the villus morphology, increased the numbers of goblet cells and lymphocytes, attenuated the mRNA overexpression of HSP70, HSP90 and NF-kappaB on the 6th, 10th and 15th day of heat stress (P < 0.05), and activated the expression of EGF (P < 0.05) in the jejunal mucosa. Resveratrol reduced protein expression of HSP70, HSP90 and NF kappaB in the jejunal villi after 15 days of heat stress, and increased EGF expression from the lamina propria toward the epithelial cells of the villi. These results suggest that dietary resveratrol offers a potential nutritional strategy to improve the intestinal morphology and alleviate jejunum mucosa injuries by modulating the mRNA and protein expression of HSPs, and the epithelial growth factor and transcription factor in black-boned chickens subjected to circular heat stress. PMID- 26843444 TI - Oral nucleos(t)ide analogues reduce recurrence and death in chronic hepatitis B related hepatocellular carcinoma. AB - BACKGROUND: In patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC), high viral load was associated with tumour recurrence and deaths. AIMS: To investigate the effect of nucleos(t)ide analogues (NA) on the clinical outcomes after different HCC treatments. METHODS: A territory-wide cohort study was conducted using the database from Hospital Authority. We identified CHB patients with HCC by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes in 2000-2012. HCC treatments, NA use and laboratory parameters were retrieved. The primary endpoint was HCC recurrence and death. A 3-month landmark analysis was used to evaluate the primary outcome in patients with or without NA treatment. RESULTS: A total of 2198 CHB patients (1230 NA-untreated and 968 NA-treated) with HCC, receiving at least one type of HCC treatment were included in the analysis. At a median follow-up of 2.8 (IQR 1.4-4.9) years, tumour recurrence and death occurred in 451 (36.7%) and 578 (47.0%) untreated patients; and in 216 (22.3%) and 301 (31.1%) NA-treated patients respectively. NA therapy reduced the risk of overall HCC recurrence [adjusted sub-hazard ratio (SHR) 0.63, 95% confidence interval (CI) 0.49-0.80; P < 0.001]. The effect was most obvious in patients undergoing resection (SHR = 0.58, 95% CI = 0.37-0.91, P = 0.018). The possibility of NA therapy reducing the risk of death (HR = 0.82, 95% CI = 0.64-1.03, P = 0.092), is most obvious in resection subgroup (HR = 0.64, 95% CI = 0.41-0.99, P = 0.050) but insignificant in the other treatment groups. CONCLUSION: Our findings show that nucleos(t)ide analogues treatment reduces the risk of HCC recurrence in patients with chronic hepatitis B treated by surgical resection. PMID- 26843446 TI - Sugar-sweetened beverage intake and its associations with cardiometabolic risks among adolescents. AB - BACKGROUND: Investigations on sugar-sweetened beverage (SSB) intake and cardiometabolic risks among Asians are scant. OBJECTIVES: This study aimed to examine associations between SSB intake and cardiometabolic risks among Malaysian adolescents. METHODS: Anthropometric data, blood pressure (BP), fasting blood glucose (FBG), lipid profiles and insulin levels measured involved 873 adolescents (aged 13 years). SSB intake, dietary patterns and physical activity level (PAL) were self-reported. RESULTS: Mean SSB consumption was 177.5 mL day-1 with significant differences among ethnicities (Malay, Chinese, Indians and Others) (p < 0.05). SSB intake was deleteriously associated with increased waist circumference, elevated triglycerides, FBG, insulin, insulin resistance and low HDL-cholesterol, independent of PAL, body mass index and dietary patterns. Significant U-shaped and inverse trends were noted between SSB intake and LDL cholesterol and BP, respectively. CONCLUSION: Sugar-sweetened beverage intake was unfavourably associated with cardiometabolic health outcomes among young adolescents. Concerted efforts towards healthy hydration are imperative to mitigate risk of cardiometabolic events. PMID- 26843445 TI - Robot-assisted versus open radical hysterectomy: A multi-institutional experience for early-stage cervical cancer. AB - OBJECTIVE: To compare perioperative and clinico-pathological outcomes of patients with early-stage cervical cancer who underwent robot-assisted radical hysterectomy (RRH) and open radical hysterectomy (ORH). METHODS: This retrospective multi-center study abstracted demographic, clinico-pathological and perioperative outcomes data from medical records of 491 cervical cancer patients treated with RRH (n = 259) ORH (n = 232) between 2005 and 2011 at two American and one Norwegian University Cancer Centres. RESULTS: Mean estimated blood loss (EBL) and transfusion rates were less for RRH than for ORH (97 vs. 49 mL, p < 0.001, and 3% vs. 7%, p = 0.018, respectively). Mean length of hospital stay (LOS) was significantly shorter in RRH versus ORH (1.8 vs. 5.1 days, p < 0.001). Mean operative time was longer for RRH than ORH (220 vs. 156 min, p < 0.001). Although overall complications were similar (p = 0.49), intra-operative complications were less common in the RRH group than ORH (4% vs. 10%, p = 0.004). In multivariate regression analyses longer operative time, less EBL and intra operative complications, shorter LOS, and more pre-operative cone were significantly associated with RRH versus ORH. Recurrence and death rates were not statistically different for the two groups at a mean follow-up time of 39 months (p = 1.00 and p = 0.48, respectively). CONCLUSIONS: RRH had improved clinical outcomes compared to ORH in the treatment of early-stage cervical cancer in terms of EBL, intra-operative complications, transfusion rates, LOS, and pre-operative cone. Disease recurrence and survival were comparable for the two procedures. PMID- 26843447 TI - The Infertility of Repeat-Breeder Cows During Summer Is Associated with Decreased Mitochondrial DNA and Increased Expression of Mitochondrial and Apoptotic Genes in Oocytes. AB - Oocyte quality is known to be a major cause of infertility in repeat-breeder (RB) and heat-stressed dairy cows. However, the mechanisms by which RB oocytes become less capable of supporting embryo development remain largely unknown. Thus, the aim of this study was to investigate whether the decreased oocyte competence of RB cows (RBs) during summer is associated with an altered gene expression profile and a decrease in mitochondrial DNA (mtDNA) copy number. Therefore, oocytes collected from heifers, non-RBs in peak lactation (PLs), and RBs were used to evaluate mtDNA amounts as well as the expression levels of genes associated with the mitochondria (MT-CO1, NRF1, POLG, POLG2, PPARGC1A, and TFAM), apoptosis (BAX, BCL2, and ITM2B), and oocyte maturation (BMP15, FGF8, FGF10, FGF16, FGF17, and GDF9). The oocytes retrieved from RBs during winter contained over eight times more mtDNA than those retrieved from RBs during summer. They also contained significantly less mtDNA than oocytes retrieved from heifers and PLs during summer. Moreover, the expression of mitochondria- (NRF1, POLG, POLG2, PPARGC1A, and TFAM) and apoptosis-related (BAX and ITM2B) genes, as well as of GDF9, in RB oocytes collected during summer was significantly greater than that in oocytes collected from heifers and PLs during the same season. In oocytes from heifers and PLs, the expression levels of these genes were lower in those collected during summer compared with winter, but this difference was not observed in oocytes collected from RBs. Altogether, these data provide evidence of altered gene expression and reduced mtDNA copy number in the oocytes collected from RBs during summer. This indicates a loss of fertility in RBs during summer, which might be caused by a possible mitochondrial dysfunction associated with a greater chance of oocytes to undergo apoptosis. PMID- 26843448 TI - Constitutive Notch Signaling Causes Abnormal Development of the Oviducts, Abnormal Angiogenesis, and Cyst Formation in Mouse Female Reproductive Tract. AB - The Notch signaling pathway is critical for the differentiation of many tissues and organs in the embryo. To study the consequences of Notch1 gain-of-function signaling on female reproductive tract development, we used a cre-loxP strategy and Amhr2-cre transgene to generate mice with conditionally activated Notch1 (Rosa(Notch1)). The Amhr2-cre transgene is expressed in the mesenchyme of developing female reproductive tract and in granulosa cells in the ovary. Double transgenic Amhr2-cre, Rosa(Notch1) females were infertile, whereas control Rosa(Notch1) mice had normal fertility. All female reproductive organs in mutants showed hemorrhaging of blood vessels progressing with age. The mutant oviducts did not develop coiling, and were instead looped around the ovary. There were multiple blockages in the lumen along the oviduct length, creating a barrier for sperm or oocyte passage. Mutant females demonstrated inflamed uteri with increased vascularization and an influx of inflammatory cells. Additionally, older females developed ovarian, oviductal, and uterine cysts. The significant change in gene expression was detected in the mutant oviduct expression of Wnt4, essential for female reproductive tract development. Similar oviductal phenotypes have been detected previously in mice with activated Smo and in beta-catenin, Wnt4, Wnt7a, and Dicer conditional knockouts, indicating a common regulatory pathway disrupted by these genetic abnormalities. PMID- 26843450 TI - Infection Prevalence, Bacterial Loads, and Transmission Efficiency in Oropsylla montana (Siphonaptera: Ceratophyllidae) One Day After Exposure to Varying Concentrations of Yersinia pestis in Blood. AB - Unblocked fleas can transmit Yersinia pestis, the bacterium that causes plague, shortly (<=4 d) after taking an infectious bloodmeal. Investigators have measured so-called early-phase transmission (EPT) efficiency in various fleas following infection with highly bacteremic blood (>=108 cfu/ml). To date, no one has determined the lower limit of bacteremia required for fleas to acquire and transmit infection by EPT, though knowing this threshold is central to determining the length of time a host may be infectious to feeding fleas. Here, we evaluate the ability of Oropsylla montana (Baker) to acquire and transmit Y. pestis after feeding on blood containing 103 to 109 cfu/ml. We evaluated the resulting infection prevalence, bacterial loads, and transmission efficiency within the early-phase time period at 1 d postinfection. Fleas acquired infection from bacteremic blood across a wide range of concentrations, but transmission was observed only when fleas ingested highly bacteremic blood. PMID- 26843449 TI - Gq/11-Dependent Changes in the Murine Ovarian Transcriptome at the End of Gestation. AB - Parturition in rodents is highly dependent on the engagement of the luteal prostaglandin F2 alpha receptor, which, through activation of the Gq/11 family of G proteins, increases the expression of Akr1c18, leading to an increase in progesterone catabolism. To further understand the involvement of Gq/11 on luteolysis and parturition, we used microarray analysis to compare the ovarian transcriptome of mice with a granulosa/luteal cell-specific deletion of Galphaq/11 with their control littermates on Day 18 of pregnancy, when mice from both genotypes are pregnant, and on Day 22, when mice with a granulosa/luteal cell-specific deletion of Galphaq/11 are still pregnant but their control littermates are 1-2 days postpartum. Ovarian genes up-regulated at the end of gestation in a Galphaq/11 -dependent fashion include genes involved in focal adhesion and extracellular matrix interactions. Genes down-regulated at the end of gestation in a Galphaq/11-dependent manner include Serpina6 (which encodes corticosteroid-binding globulin); Enpp2 (which encodes autotaxin, the enzyme responsible for the synthesis of lysophosphatidic acid); genes involved in protein processing and export; reproductive genes, such as Lhcgr; the three genes needed to convert progesterone to estradiol (Cyp17a1, Hsd17b7, and Cyp19a1); and Inha. Activation of ovarian Gq/11 by engagement of the prostaglandin F2 alpha receptor on Day 18 of pregnancy recapitulated the regulation of many but not all of these genes. Thus, although the ovarian transcriptome at the end of gestation is highly dependent on the activation of Gq/11, not all of these changes are dependent on the actions of prostaglandin F2 alpha. PMID- 26843452 TI - A general decline in cerebrospinal fluid flow and optic nerve compartmentation: are these sequential steps leading to toxicity in normal-tension glaucoma? PMID- 26843451 TI - Human C5a Protein Participates in the Mosquito Immune Response Against Dengue Virus. AB - Dengue virus (DENV) is transmitted by Aedes spp mosquitoes during a bloodmeal uptake. The bloodmeal consists of host cells, immune factors, and possibly blood borne pathogens, such as arboviruses. Human cells and immune-related factors, like the complement system, can remain active in the bloodmeal and may be able to interact with pathogens in the mosquito. Previous studies have shown that active complement proteins impact Plasmodium parasite viability in the Anopheles midgut. Thus, we investigated the effects of the human complement on DENV infection in the midgut of Aedes aegypti. Our findings indicate that mosquitoes receiving DENV mixed with normal non-inactivated human serum showed significantly lower viremia than those fed with heat-inactivated serum. This implies that human complement may act to limit DENV infection in the mosquito midgut. In addition, we found that human complement C5a protein was able to directly communicate with mosquito cells, affecting the cell antiviral response against DENV. Our results also show that human C5a protein is able to interact with several membrane-bound mosquito proteins. Together these results suggest an important role of human complement protein in DENV transmission. PMID- 26843453 TI - Elevated expression of ABCB5 in ocular surface squamous neoplasia. AB - ATP-binding cassette subfamily B member 5 (ABCB5) is a new member of the ATP binding cassette superfamily and has been reported as a novel marker for limbal stem cell (LSC), which is essential for corneal homeostasis. ABCB5 expression has also been discovered in the subpopulation of several cancer cells containing the cancer stem cell (CSC). However, the pathogenetic relationship between LSC and CSC and ABCB5 in the ocular surface squamous neoplasm (OSSN) is still entirely unknown. To improve understanding of the role of ABCB5 in OSSN, we performed immunohistochemistry for ABCB5 in nine OSSN case series. While expression of ABCB5 is restricted to the basal epithelial cell layer in the normal limbus, elevated expressions of ABCB5 were clearly observed in all OSSN, and there was some breadth in the range of intensity of ABCB5 expression. Interestingly, the elevated expression patterns of ABCB5 in OSSN could be classified in three categories: perivascular, marginal and diffuse patterns. Our findings demonstrated for the first time that the expression of ABCB5 was upregulated in OSSN and that elevated expression of ABCB5 may be involved in the pathogenesis of OSSN. PMID- 26843454 TI - Massive ovarian oedema: a misleading clinical entity. AB - BACKGROUND: Massive ovarian oedema is a rare non-neoplastic clinicopathologic entity has a higher incidence in women during their second and third life decade. The oedema can be presented in one or both ovaries as a result of partial intermittent torsion of the ovarian pedicle that interferes to the venal and lymphatic drainage of the ovary. CASE PRESENTATION: We present a clinical case of a 16 year old with massive ovarian oedema and we performed a review of the literature. The pathophysiology of this entity is very complex. We tried to perform a complete review of the literature and focus on the complexity of this entity as far as its pathophysiological backround is concerned and as far as its clinical presentation is concerned. CONCLUSIONS: In conclusion, massive ovarian oedema is a rare, multi disease mimicking clinical entity, with an acute or progressive clinical presentation. It has also to be a part of our differential diagnosis in cases of acute abdominal pain and we have to try to treat her conservatively, in order to preserve fertility. PMID- 26843455 TI - Molecular mechanism of apoptosis induction by Gaillardin, a sesquiterpene lactone, in breast cancer cell lines : Gaillardin-induced apoptosis in breast cancer cell lines. AB - Medicinal plant extracts have been widely used for cancer treatment. Gaillardin is a natural sesquiterpene lactone that has recently been reported to have anticancer properties. The ability to induce apoptosis is an important property of a candidate anticancer drug, which discriminates between anticancer drugs and toxic compounds. The current study was therefore carried out to address the issue if Gaillardin is able to induce apoptosis in the breast cancer cell lines MCF-7 and MDA-MB-468 and to determine the underlying mechanism of its anticancer effects. Apoptosis induction by Gaillardin treatment was confirmed by annexin V FITC/PI staining, and caspase-3,-6, and-9 activation. Using Western blot analysis, we found that Gaillardin upregulated the pro-apoptotic protein Bax and p53 and downregulated the anti-apoptotic protein Bcl-2. Moreover, the apoptotic effect of Gaillardin was also related to ROS production and loss of mitochondrial membrane potential (DeltaPsim). Taken together, these results demonstrate that Gaillardin can inhibit proliferation of breast cancer cells via inducing mitochondrial apoptotic pathway and therefore, might be a promising molecule in cancer chemoprevention or chemotherapy. PMID- 26843456 TI - High-resolution oesophageal manometry and 24-hour impedance-pH study in systemic sclerosis patients: association with clinical features, symptoms and severity. AB - OBJECTIVES: To evaluate the associations between objectively measured gastroesophageal involvement using high-resolution manometry and 24- hour impedance-pH study, and clinical presentations in systemic sclerosis (SSc) patients. METHODS: This cross-sectional study was conducted in University of Malaya Medical Centre (UMMC) with 31 consecutive SSc patients recruited into this study. Clinical symptoms of gastroesophageal involvement, high-resolution impedance-manometry and 24-hour impedance-pH monitoring were assessed. Their associations with serological features and other organ involvement were evaluated. RESULTS: Twenty-five (80.6%) patients had gastroesophageal reflux disease (GORD) symptoms, mainly heartburn (45.1%), regurgitation (32.2%) and dysphagia (29%). Using manometry, oesophageal dysmotility was detected in 24 (88.9%) patients, while hypotensive lower oesophageal sphincter (LOS) was observed in 17 (63%) patients. 21 (84%) patients had GORD based on pH study. Hypotensive LOS was significantly associated with presence of digital ulcers. The main gastroesophageal symptoms were absent in majority of the SSc patients including in those with severe gastroesophageal manifestations demonstrating failed peristalsis >75%, hypotensive LOS, Demeester score >200 and acid reflux >200 per day. Demeester score >200 is associated with severity of GORD symptoms. Demeester score >200 was also associated with restrictive lung pattern (p=0.001). Significant association between GORD severity (daily number of acid reflux episodes >200) and pulmonary fibrosis was seen (p=0.030). CONCLUSIONS: The presence and severity of gastroesophageal symptoms may not accurately reflect the seriousness of oesophageal involvement. GORD severity is associated with presence of restrictive lung pattern and pulmonary fibrosis. Oesophageal manometry and 24 hour pH study should be considered more frequently in the assessment of SSc patients. PMID- 26843457 TI - Practice variation in the structure of stroke rehabilitation in four rehabilitation centres in the Netherlands. AB - OBJECTIVE: To describe practice variation in the structure of stroke rehabilitation in 4 specialized multidisciplinary rehabilitation centres in the Netherlands. DESIGN AND METHODS: A multidisciplinary expert group formulated a set of 23 elements concerning the structure of inpatient and outpatient stroke rehabilitation, categorized into 4 domains: admission-related (n = 7), treatment related (n = 10), client involvement-related (n = 2), and facilities-related (n = 4). In a cross-sectional study in 4 rehabilitation centres data on the presence and content of these elements were abstracted from treatment programmes and protocols. In a structured expert meeting consensus was reached on the presence of practice variation per element. RESULTS: Practice variation was observed in 22 of the 23 structure elements. The element "strategies for patient involvement" appeared similar in all rehabilitation centres, whereas differences were found in the elements regarding admission, exclusion and discharge criteria, patient subgroups, care pathways, team meetings, clinical assessments, maximum time to admission, aftercare and return to work modules, health professionals, treatment facilities, and care-giver involvement. CONCLUSION: Practice variation was found in a wide range of aspects of the structure of stroke rehabilitation. PMID- 26843458 TI - Prospective heart tracking for whole-heart magnetic resonance angiography. AB - PURPOSE: To develop a prospective respiratory-gating technique (Heart-NAV) for use with contrast-enhanced three-dimensional (3D) inversion recovery (IR) whole heart magnetic resonance angiography (MRA) acquisitions that directly tracks heart motion without creating image inflow artifact. METHODS: With Heart-NAV, one of the startup pulses for the whole-heart steady-state free precession MRA sequence is used to collect the centerline of k-space, and its one-dimensional reconstruction is fed into the standard diaphragm-navigator (NAV) signal analysis process to prospectively gate and track respiratory-induced heart displacement. Ten healthy volunteers underwent non-contrast whole-heart MRA acquisitions using the conventional diaphragm-NAV and Heart-NAV with 5 and 10-mm acceptance windows in a 1.5T scanner. Five patients underwent contrast-enhanced IR whole-heart MRA using a diaphragm-NAV and Heart-NAV with a 5-mm acceptance window. RESULTS: For non-contrast whole-heart MRA with both the 5 and 10-mm acceptance windows, Heart NAV yielded coronary artery vessel sharpness and subjective visual scores that were not significantly different than those using a conventional diaphragm-NAV. Scan time for Heart-NAV was 10% shorter (p < 0.05). In patients undergoing contrast-enhanced IR whole-heart MRA, inflow artifact was seen with the diaphragm NAV but not with Heart-NAV. CONCLUSION: Compared with a conventional diaphragm NAV, Heart-NAV achieves similar image quality in a slightly shorter scan time and eliminates inflow artifact. Magn Reson Med 77:759-765, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26843459 TI - Role of IL-17A rs2275913 and IL-17F rs763780 polymorphisms in risk of cancer development: an updated meta-analysis. AB - Single nucleotide polymorphisms (SNPs) in the interleukin-17 (IL-17) gene have been shown to be correlated with susceptibility to cancer. However, various studies report different results of this association. The aim of the present work was to clarify the effects of IL-17A G197A (rs2275913) and IL-17F T7488C (rs763780) polymorphisms on cancer risk. We performed systematic searches of the PubMed and CNKI databases to obtain relevant publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association of rs2275913 and rs763780 polymorphisms with cancer risk. Data were extracted from the selected studies, and statistical analysis was conducted using the STATA software. Our results indicated that rs2275913 and rs763780 polymorphisms significantly increase cancer risk, especially in gastric cancers. Subgroup analysis suggested the existence of a significant correlation between rs763780 polymorphism and cancer susceptibility in Caucasian populations. This updated meta-analysis confirms that rs2275913 and rs763780 polymorphisms are highly associated with increased risk for multiple forms of cancer. PMID- 26843460 TI - Myocardial Oxidative Stress in Infants Undergoing Cardiac Surgery. AB - Cardiac surgery for congenital heart disease often necessitates a period of myocardial ischemia during cardiopulmonary bypass and cardioplegic arrest, followed by reperfusion after aortic cross-clamp removal. In experimental models, myocardial ischemia-reperfusion is associated with significant oxidative stress and ventricular dysfunction. A prospective observational study was conducted in infants (<1 year) who underwent elective surgical repair of a ventricular septal defect (VSD) or tetralogy of Fallot (TOF). Blood samples were drawn following anesthetic induction (baseline) and directly from the coronary sinus at 1, 3, 5, and 10 min following aortic cross-clamp removal. Samples were analyzed for oxidant stress using assays for thiobarbituric acid-reactive substances, protein carbonyl, 8-isoprostane, and total antioxidant capacity. For each subject, raw assay data were normalized to individual baseline samples and expressed as fold change from baseline. Results were compared using a one-sample t test with Bonferroni correction for multiple comparisons. Sixteen patients (ten with TOF and six with VSD) were enrolled in the study, and there were no major postoperative complications observed. For the entire cohort, there was an immediate, rapid increase in myocardial oxidative stress that was sustained for 10 min following aortic cross-clamp removal in all biomarker assays (all P < 0.01), except total antioxidant capacity. Infant cardiac surgery is associated with a rapid, robust, and time-dependent increase in myocardial oxidant stress as measured from the coronary sinus in vivo. Future studies with larger enrollment are necessary to assess any association between myocardial oxidative stress and early postoperative outcomes. PMID- 26843461 TI - Change in Pediatric Functional Classification During Treatment and Morbidity and Mortality in Children with Pulmonary Hypertension. AB - Despite advances in therapy, outcomes for children with pulmonary hypertension remain poor. We sought to assess the validity of a pediatric-specific functional classification system for pulmonary hypertension (PH) in a heterogeneous population of children with PH diagnosed by echocardiogram or cardiac catheterization. A single-center, retrospective study of 65 infants and children with PH was performed. Pediatric Functional Class (FC) at diagnosis, at last visit, and change in FC over time were evaluated for their association with mortality and PH-associated morbidity in univariate, time-to-event, and multivariate regression analyses. Median age at PH diagnosis was 5.3 months (0 days-12.7 years). Twenty-five children (38 %) had idiopathic PH or PH secondary to congenital heart disease, one (2 %) had left heart disease, and 39 (60 %) had PH secondary to respiratory disease. Mortality was 25 % (16/63), primarily in the first year of follow-up. FC at diagnosis was not significantly associated with survival (p = 0.22), but higher FC (more impaired) at last visit (p < 0.001) and change in FC over time (HR 2.3, 95 % confidence interval 1.3-4, p = 0.0003) were associated with mortality. Higher FC at last visit was associated with greater days of hospitalization in the intensive care unit per year (p = 0.006) and history of cardiac arrest (p = 0.012) and syncope (p = 0.02). Although pediatric FC at diagnosis was not predictive of mortality, response to therapy (as assessed by change in FC over time and FC at last visit) was associated with morbidity and mortality in this heterogeneous cohort. Multicenter prospective studies are necessary to further validate these findings. PMID- 26843462 TI - Inhibition of Chikungunya Virus Replication by 1-[(2-Methylbenzimidazol-1-yl) Methyl]-2-Oxo-Indolin-3-ylidene] Amino] Thiourea(MBZM-N-IBT). AB - Chikungunya virus (CHIKV) infection is one of the most challenging human Arboviral infections with global significance and without any specific antiviral. In this investigation, 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3 ylidene] amino] thiourea (MBZM-N-IBT) was synthesised as a molecular hybrid of 2 methyl benzimidazole and isatin-beta-thiosemicarbazone and its anti-CHIKV property was evaluated. The release of infectious virus particles was calculated by plaque assay, expression profile of viral RNA was estimated by RT-PCR and viral protein profiles were assessed by Western blot and FACS analyses. The safety index of MBZM-N-IBT was found to be >21. The CHIKV infectious viral particle formation was abrogated around 76.02% by MBZM-N-IBT during infection in mammalian system and the viral RNA synthesis was reduced by 65.53% and 23.71% for nsP2 and E1 respectively. Surprisingly, the viral protein levels were reduced by 97% for both nsP2 and E2. In the time-of-addition experiment it abrogated viral infection at early as well as late phase of viral life cycle, which indicates about multiple mechanisms for its anti-CHIKV action. In silico analysis justified development of MBZM-N-IBT with good affinities for potential target proteins of CHIKV and related virus. With predictions of good drug-likeness property, it shows potential of a drug candidate which needs further experimental validation. PMID- 26843464 TI - Factors Associated With Point-of-Care Treatment Decisions for Hidradenitis Suppurativa. AB - IMPORTANCE: Studies evaluating factors associated with disease severity in hidradenitis suppurativa (HS) are limited, and the existing data are controversial. It is also unclear whether severity assessed by HS scoring methods correlate with partnered decision-making on treatment strategies, and thus the clinical relevance of these severity assessments is unknown. OBJECTIVE: To assess factors associated with disease severity as measured by point-of-care decisions on receipt or escalation of treatment for HS. DESIGN, SETTING, AND PARTICIPANTS: The retrospective cohort comprised 437 patients with HS ages 18 to 64 years at enrollment with at least 5 monitoring periods of 3 months' duration. The study was performed at an academic medical center. MAIN OUTCOMES AND MEASURES: Receipt of treatment and treatment escalation. RESULTS: The average monitoring time of patients with HS was 4.2 person-years. The frequency of patients with HS with no treatment decreased over the monitoring period, while the frequency for receipt of treatment increased. Care by a dermatologist (odds ratio [OR], 6.7; 95% CI, 5.2-8.6) provided the strongest predictor of having received treatment for HS, and it was also associated with increased odds of escalating treatment (OR, 3.0; 95% CI, 2.4-3.7). Tobacco smoking was associated with treatment escalation (OR, 1.4; 95% CI, 1.1-1.7) over time, whereas obesity was not associated with treatment or escalation. The likelihood of receiving (OR, 1.4; 95% CI, 1.2-1.8) or escalating treatment (OR, 1.2; 95% CI, 1.0-1.4) was increased between ages 18 and 39 years. Male sex was not associated with treatment escalation. CONCLUSIONS AND RELEVANCE: Clinician type, tobacco smoking, and age may be important clinical factors that patients and clinicians may consider in developing partnered short- and long-term treatment strategies. Obesity and sex do not seem to influence treatment decisions for HS. PMID- 26843463 TI - GABAergic interneurons form transient layer-specific circuits in early postnatal neocortex. AB - GABAergic interneurons play key roles in cortical circuits, yet little is known about their early connectivity. Here we use glutamate uncaging and a novel optogenetic strategy to track changes in the afferent and efferent synaptic connections of developing neocortical interneuron subtypes. We find that Nkx2-1 derived interneurons possess functional synaptic connections before emerging pyramidal cell networks. Subsequent interneuron circuit maturation is both subtype and layer dependent. Glutamatergic input onto fast spiking (FS), but not somatostatin-positive, non-FS interneurons increases over development. Interneurons of both subtype located in layers (L) 4 and 5b engage in transient circuits that disappear after the somatosensory critical period. These include a pathway mediated by L5b somatostatin-positive interneurons that specifically targets L4 during the first postnatal week. The innervation patterns of immature cortical interneuron circuits are thus neither static nor progressively strengthened but follow a layer-specific choreography of transient connections that differ from those of the adult brain. PMID- 26843465 TI - Glycoprotein B of equine herpesvirus type 1 has two recognition sites for subtilisin-like proteases that are cleaved by furin. AB - Glycoprotein B (gB) of equine herpesvirus type 1 (EHV-1) is predicted to be cleaved by furin in a fashion similar to that of related herpesviruses. To investigate the contribution of furin-mediated gB cleavage to EHV-1 growth, canonical furin cleavage sites were mutated. Western blot analysis of mutated EHV 1 gB showed that it was cleaved at two positions, 518RRRR521 and 544RLHK547, and that the 28 aa between the two sites were removed after cleavage. Treating infected cells with either convertase or furin inhibitors reduced gB cleavage efficiency. Further, removal of the first furin recognition motif did not affect in vitro growth of EHV-1, while mutation of the second motif greatly affected virus growth. In addition, a second possible signal peptide cleavage site was identified for EHV-1 gB between residues 98 and 99, which was 13 aa downstream of that previously identified. PMID- 26843466 TI - Role of telerehabilitation in patients following total knee arthroplasty: Evidence from a systematic literature review and meta-analysis. AB - Introduction Increased physical activity and functional ability are the goals of total knee replacement surgery. Therefore, adequate rehabilitation is required for the recovery of patients after discharge from hospital following total knee arthroplasty (TKA). This systematic literature review aimed to evaluate the effectiveness of home telerehabilitation in patients who underwent TKA. Methods Studies published in the English language between 2000 and 2014 were retrieved from Embase, PubMed, and Cochrane databases using relevant search strategies. Two researchers independently reviewed the studies as per the Cochrane methodology for systematic literature review. We considered telerehabilitation sessions as those that were conducted by experienced physiotherapists, using videoconferencing to patients' homes via an internet connection. The outcomes assessed included: knee movement (knee extension and flexion); quadriceps muscle strength; functional assessment (the timed up-and-go test); and assessment of pain, stiffness, and functional capacity using the Western Ontario and McMaster Universities Osteoarthritis Index and visual analogue scale for pain. Results In total, 160 potentially relevant studies were screened. Following the screening of studies as abstracts and full-text publications, six primary publications (four randomized controlled trials, one non-randomized controlled trial, and one single arm trial) were included in the review. Patients experienced high levels of satisfaction with the use of telerehabilitation alone. There was no significant difference in change in active knee extension and flexion in the home telerehabilitation group as compared to the control group (mean difference (MD) 0.52, 95% CI -1.39 to 0.35, p = 0.24 and MD 1.14, 95% CI -0.61 to 2.89, p = 0.20, respectively). The patients in the home telerehabilitation group showed improvement in physical activity and functional status similar to patients in the conventional therapy group. Discussion The evidence from this systematic literature review demonstrated that telerehabilitation is a practical alternative to conventional face-to-face rehabilitation therapy in patients who underwent TKA. PMID- 26843467 TI - Platelet-released growth factors induce the antimicrobial peptide human beta defensin-2 in primary keratinocytes. AB - Platelet-released growth factors (PRGF) and its related clinically used formulations [e.g. Vivostat platelet-rich fibrin (PRF((r)) )] are thrombocyte concentrate lysates that support healing of chronic, hard-to-heal and infected wounds. Human beta-defensin-2 (hBD-2) is an antimicrobial peptide expressed in human keratinocytes exhibiting potent antimicrobial activity against wound related bacteria. In this study, we analysed the influence of PRGF on hBD-2 expression in human primary keratinocytes and the influence of Vivostat PRF((r)) on hBD-2 expression in experimentally generated skin wounds in vivo. Treatment of primary keratinocytes with PRGF caused a significant increase in hBD-2 gene and protein expressions in a concentration- and time-dependent manner. The use of blocking antibodies revealed that the PRGF-mediated hBD-2 induction was partially mediated by the epidermal growth factor receptor and the interleukin-6 receptor (IL-6R). Luciferase gene reporter assays indicated that the hBD-2 induction through PRGF required activation of the transcription factor activator protein 1 (AP-1), but not of NF-kappaB. In concordance with these cell culture data, Vivostat PRF((r)) induced hBD-2 expression when applied to experimentally generated skin wounds. Together, our results indicate that the induction of hBD-2 by thrombocyte concentrate lysates can contribute to the observed beneficial effects in the treatment of chronic and infected wounds. PMID- 26843468 TI - Baseline factor VIII plasma levels and age at first bleeding in patients with severe forms of von Willebrand disease. AB - INTRODUCTION: von Willebrand disease (VWD) is the most common inherited bleeding disorder. The age of bleeding onset is highly variable, also in patients with similar degree of severity. AIM: The primary aim of this study was to evaluate whether baseline factor VIII (FVIII) plasma levels correlate with age at first bleeding in patients with extremely low levels of VWF:RCo (<6 IU dL(-1) ). METHODS: One hundred and three patients with VWF:RCo <6 IU dL(-1) (6 VWD1, 73 VWD2 and 24 VWD3) undergoing a medical examination between September 2010 and September 2013 were included. The relationship between baseline FVIII levels and age at first bleeding was tested in a multivariable linear regression model, adjusting for sex. RESULTS: The median age at first bleeding was lower in patients with VWD3 than in those with severe forms of VWD1 or VWD2 (1 year vs. 7 and 8 years, respectively, P < 0.0001). A positive non-linear relationship between FVIII levels and age at first bleeding was found, the latter increasing by 5 years for every 10 IU dL(-1) increase of FVIII (beta = 4.95 [95% CI: 2.02 7.87]) until levels of 30 IU dL(-1) , after which the age increased slowly. This relationship was not found in VWD 2A and 2B. In 65 patients (63%) there was a more than 6-month delay between bleeding onset and VWD diagnosis, with no difference over decades. CONCLUSIONS: Baseline FVIII plasma levels influence the age at bleeding onset in VWD patients with extremely low levels of VWF:RCo, except in those with types 2A and 2B. PMID- 26843469 TI - F-actin cytoskeleton and the fate of organelles in chromaffin cells. AB - In addition to playing a fundamental structural role, the F-actin cytoskeleton in neuroendocrine chromaffin cells has a prominent influence on governing the molecular mechanism and regulating the secretory process. Performing such roles, the F-actin network might be essential to first transport, and later locate the cellular organelles participating in the secretory cycle. Chromaffin granules are transported from the internal cytosolic regions to the cell periphery along microtubular and F-actin structures. Once in the cortical region, they are embedded in the F-actin network where these vesicles experience restrictions in motility. Similarly, mitochondria transport is affected by both microtubule and F actin inhibitors and suffers increasing motion restrictions when they are located in the cortical region. Therefore, the F-actin cortex is a key factor in defining the existence of two populations of cortical and perinuclear granules and mitochondria which could be distinguished by their different location and mobility. Interestingly, other important organelles for controlling intracellular calcium levels, such as the endoplasmic reticulum network, present clear differences in distribution and much lower mobility than chromaffin vesicles and mitochondria. Nevertheless, both mitochondria and the endoplasmic reticulum appear to distribute in the proximity of secretory sites to fulfill a pivotal role, forming triads with calcium channels ensuring the fine tuning of the secretory response. This review presents the contributions that provide the basis for our current view regarding the influence that F-actin has on the distribution of organelles participating in the release of catecholamines in chromaffin cells, and summarizes this knowledge in simple models. In chromaffin cells, organelles such as granules and mitochondria distribute forming cortical and perinuclear populations whereas others like the ER present homogenous distributions. In the present review we discuss the role of transport systems and the existence of an F actin cortical structure as the main factors behind the formation of organelle subpopulations in this neuroendocrine cell model. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015). Cover image for this issue: doi: 10.1111/jnc.13322. PMID- 26843470 TI - Short- and long-term outcomes of pneumonectomy in a tertiary center. AB - BACKGROUND: Surgery is the most important therapeutic modality for lung cancer. Surgical outcomes are normally reported as 30-day or 90-day mortality or 5-year survival; 10-year survival is rarely mentioned in national data or international studies. METHODS: Three hundred and six patients (79% male) underwent pneumonectomy, mainly for lung cancer, from January 1998 to February 2013. Their short- and long-term outcomes up to September 2014 were analyzed retrospectively. The mean age was 64 years (range 22-82 years) and 24% were aged >=70 years. Thoracoscore was used to calculate the risk of hospital mortality. RESULTS: Operative mortality was 4.5% whereas predicted mortality was 8%. The operative mortality for cancer patients was 3.3%; the national mortality for lung cancer is 6.5%. Only 2 patients died in hospital after a pneumonectomy in the last 5 years. Half of the patients who died in hospital were >=70 years old; 29% (4 patients) died after urgent operations for nonmalignant disease. Overall 5- and 10-year survival was 32% and 20%. Median and mean survival was 26 and 57 months, respectively. Long-term survival was better in females aged <70 years, in left pneumonectomy patients, and in those with squamous cell lung cancer. CONCLUSION: Our mortality for pneumonectomy was 50% less than the national mortality rate and significantly lower than that predicted by the Thoracoscore for lung cancer. This confirms that pneumonectomy is still an effective modality for the treatment of lung cancer, with low operative mortality and good long-term survival, especially in younger patients. PMID- 26843471 TI - Identification, characterization, and high-performance liquid chromatography quantification of process-related impurities in vonoprazan fumarate. AB - High-performance liquid chromatography analysis of vonoprazan fumarate, a novel proton pump inhibitor drug revealed six impurities. These were identified by liquid chromatography with mass spectrometry. Further, the structures of the impurities were confirmed by synthesis followed by characterization by mass spectrometry, NMR spectroscopy, and infrared spectroscopy. On the basis of these data and knowledge of the synthetic scheme of vonoprazan fumarate, the previously unknown impurity was identified as 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl) 1H-pyrrol-3-yl]-N-methyldimethylamine, which is a new compound. The possible mechanisms by which these impurities were formed were also discussed. A high performance liquid chromatography method was optimized in order to separate, selectively detect, and quantify all process-related impurities of vonoprazan fumarate. The presented method has been validated in terms of linearity, limits of detection, and quantification, and response factors and, therefore, is highly suitable for routine analysis of vonoprazan fumarate related substances as well as stability studies. PMID- 26843473 TI - Effects of sustained release growth hormone treatment during the rehabilitation of adult severe burn survivors. AB - OBJECTIVES: The catabolic phase following burn injuries increases caloric imbalance and results in substantial weight loss because of hypermetabolism; energy expenditures as high as twice the normal limit have been documented during the first 3 weeks. Furthermore, the wound size and healing duration seem to be related to the length of stay in the intensive care unit, which results in the loss of muscle mass, the so-called sarcopenia; weakness; and physical frailty. Possible therapeutic strategies include exercises, use of anabolic steroids, or replacement with human growth hormone (hGH). To determine the clinical effects of hGH on sarcopenia after burn injuries, we compared patients who received subcutaneous hGH injections during rehabilitation with control patients who received placebo treatment. METHODS: A total of 33 patients with third degree burn injuries covering a total body surface area of >20% were randomly divided into a test group (n=18), which received 2-mg injections of sustained release hGH (SR-hGH) weekly for 3 months during rehabilitation, and a control group (n=15), which followed the same rehabilitation protocol with placebo injections. Muscular strength, cardiopulmonary function, body composition, and body weight were measured at baseline and 1 and 3 months after SR-hGH or placebo administration. RESULTS: The mean age of patients was 37.67 +/- 7.64 years in the SR-hGH group and 37.22 +/- 8.19 years in the control group, while the interval between injury and SR-hGH or placebo injection was 123.7 +/- 53.6 and 126.6 +/- 43.5 days, respectively. The oxygen consumption at the lactate threshold, maximum oxygen consumption, lean body mass, knee extensor peak torque, and insulin-like growth factor 1 (IGF-1) and adiponectin levels were significantly higher in the SR-hGH group than in the control group at 3 months. There were no differences in the body weight, systolic and diastolic blood pressure (BP), bone mineral content, percentage body fat, and burn scar characteristics between groups. CONCLUSION: Our results suggest that SR-hGH treatment during the rehabilitation of adult burn survivors positively affects physical fitness levels, muscle power, and metabolic processes, although further confirmation through research of metabolic pathways in burn survivors is required. PMID- 26843475 TI - A baby with low Apgar scores at birth. PMID- 26843472 TI - Does the GH/IGF-1 axis contribute to skeletal sexual dimorphism? Evidence from mouse studies. AB - The contribution of the gonadotropic axis to skeletal sexual dimorphism (SSD) was clarified in recent years. Studies with animal models of estrogen receptor (ER) or androgen receptor (AR) null mice, as well as mice with bone cell-specific ablation of ER or AR, revealed that both hormones play major roles in skeletal acquisition, and that estrogen regulates skeletal accrual in both sexes. The growth hormone (GH) and its downstream effector, the insulin-like growth factor-1 (IGF-1) are also major determinants of peak bone mass during puberty and young adulthood, and play important roles in maintaining bone integrity during aging. A few studies in both humans and animal models suggest that in addition to the differences in sex steroid actions on bone, sex-specific effects of GH and IGF-1 play essential roles in SSD. However, the contributions of the somatotropic (GH/IGF-1) axis to SSD are controversial and data is difficult to interpret. GH/IGF-1 are pleotropic hormones that act in an endocrine and autocrine/paracrine fashion on multiple tissues, affecting body composition as well as metabolism. Thus, understanding the contribution of the somatotropic axis to SSD requires the use of mouse models that will differentiate between these two modes of action. Elucidation of the relative contribution of GH/IGF-1 axis to SSD is significant because GH is approved for the treatment of normal children with short stature and children with congenital growth disorders. Thus, if the GH/IGF-1 axis determines SSD, treatment with GH may be tailored according to sex. In the following review, we give an overview of the roles of sex steroids in determining SSD and how they may interact with the GH/IGF-1 axis in bone. We summarize several mouse models with impaired somatotropic axis and speculate on the possible contribution of that axis to SSD. PMID- 26843474 TI - Growth hormone signaling in fibroblasts from newborn boys and prepubertal boys. AB - BACKGROUND/AIM: Responsiveness to GH in target cells is mediated by its receptor, which activates the Janus kinase-2 (JAK2) and STAT5 (signal transducers and activators of transcription 5) leading to the expression of IGF-1 and IGFALS. The aim of this study was to compare the GH signaling pathway in newborns and prepubertal boys. SUBJECTS AND METHODS: We determined the GHR protein content and the effect of stimulation with recombinant human GH (rhGH; 200ng/mL) on JAK2 and STAT5 phosphorylation in skin fibroblast cultures obtained from newborns and prepubertal boys. The transcript levels of IGFALS and IGF-I, were also studied and compared after 16h or 24h of stimulation with GH in both study groups. RESULTS: Newborn infants showed less GHR protein than the prepubertal boys. After rhGH stimulation, JAK2 and STAT5 phosphorylation was absent in skin fibroblasts from newborns, but was clearly detectable in prepubertal boys. After 16h of treatment with rhGH, IGFALS and IGF-I transcript levels increased in the prepubertal boys when compared to baseline. In newborns, however, we did not observe a response after 16 and 24h of rhGH stimulation. CONCLUSION: The significant attenuation of the GH signaling pathway observed in fibroblasts from newborn boys appears to be related to a reduction in GHR content and lack of phosphorylation of JAK2 and STAT5 in response to rhGH. This might impair STAT5 dimer formation, leading to a reduction in the transcript levels of IGFALS and IGF-I during the newborn period. PMID- 26843476 TI - The influence of a caveolin-1 mutant on the function of P-glycoprotein. AB - The genetic heterogeneity in cancer cells has an increased chance in the acquisition of new mutant such as drug-resistant phenotype in cancer cells. The phenotype of drug resistance in cancer cells could be evaluated by the number or function of drug transporters on cell membranes, which would lead to decreased intracellular anti-cancer drugs concentration. Caveolae are flask-shaped invaginations on cell membrane that function in membrane trafficking, endocytosis, and as a compartment where receptors and signaling proteins are concentrated. Caveolin-1 (CAV1) is the principal structural protein of caveolae and closely correlates with multidrug resistance in cancer cells. In a systematic study of the ubiquitin-modified proteome, lysine 176 of CAV1 was identified as a potential post-translational modification site for ubiquitination. In this article, we identified a mutation at lysine 176 to arginine (K176R) on CAV1 would interfere with the biogenesis of caveolae and broke the interaction of CAV1 with P-glycoprotein. Functional assays further revealed that K176R mutant of CAV1 in cancer cells increased the transport activity of P-glycoprotein and decreased the killing ability of anti-cancer drugs in non-small-cell lung cancer cell lines. PMID- 26843478 TI - Relationship Between Comorbid Conditions and Utilization Patterns of Immediate Breast Reconstruction Subtypes Post-mastectomy. AB - There is limited information on the influence of a patient's comorbid status on the type of immediate breast reconstruction (IBR) selected. Our aim was to provide a population-based review of the relationship between baseline comorbid conditions and IBR subtype selected. This is a retrospective cohort study using the National Surgical Quality Improvement Program database to identify IBR recipients. Multivariable regression analyses was performed to identify the association between comorbidity and IBR subtype selection (prosthetic, pedicled, and free autologous). A total of 48,096 mastectomy patients were identified, of which 17,404 patients received IBR. IBR patients were younger (51 +/- 10.4 versus 61.5 +/- 13.6 years) and had a lower body mass index (27.1 +/- 6.4 versus 28.9 +/ 7.3) relative to patients who did not pursue IBR (p < 0.001 for all). Overall, IBR patients had a significantly lower incidence of comorbid conditions. In adjusted models, patients aged 45-64 years were more likely to pursue pedicled autologous reconstruction (OR: 1.43, p < 0.001) and those older than 65 years were less likely to undergo free-autologous reconstruction (OR: 0.64, p = 0.02). Class I and II obesity was associated with pedicled (class I OR: 1.57, class II OR: 1.41) and free transfer (class I OR: 1.81, class II OR: 1.66) autologous IBR utilization (all p < 0.001). Also, smoking was related to increased chance of prosthetic reconstruction while preoperative radiotherapy was linked to free autologous IBR. IBR patients were noted to be healthier than their non-IBR counterparts, and each IBR subtype was associated with a particular comorbidity profile. This has significant implications with regard to creation of an IBR predictive model. Such a tool will improve preoperative counseling and decision making. PMID- 26843477 TI - Prognostic value of polarized macrophages in patients with hepatocellular carcinoma after curative resection. AB - As the most predominant tumour-infiltrating immune cells, tumour-associated macrophages (TAMs) are significant for fostering tumour growth, progression and metastasis. CD68-positive TAMs display dissimilarly polarized programmes comprising CD11c-positive pro-inflammatory macrophages (M1) and CD206-positive immunosuppressive macrophages (M2). The aim of this study is to determine the prognostic significance of diametrically polarized TAMs in hepatocellular carcinoma (HCC) and their application to risk stratification of patients according to their specific prognostic values. This study included 80 consecutive patients with HCC, and we evaluated diametrically polarized functional status of macrophages by immunohistochemical staining of CD68, CD11c and CD206. Prognostic values and clinicopathologic features were assessed in these patients. High versus low CD11c-positive TAM density (P = 0.005) and low versus high CD206 positive TAM density (P = 0.002) were associated with better overall survival, whereas CD68-positive TAM density had no prognostic significance (low versus high, P = 0.065). Furthermore, the presence of these positive staining macrophages did not show any prognostic significance for recurrence-free survival (all P > 0.05). Multivariate Cox regression analysis identified CD11c-positive and CD206-positive TAMs as an independent prognostic factor (P < 0.001, P = 0.031, respectively). Intratumoural infiltration of diametrically polarized TAMs, a novel identified independent prognostic factor for survival in patients with HCC, could be combined with the TNM stage and the Barcelona Clinic Liver Cancer stage to improve a risk stratification system. PMID- 26843479 TI - Erythrophagocytosis by plasmacytoid dendritic cells and monocytes is enhanced during inflammation. AB - BACKGROUND: Generation of antibodies against red blood cell (RBC) antigens can be a clinically significant problem. The underlying mechanisms that regulate the production of RBC antibodies are only partially understood; however, factors such as inflammation significantly increase the rates of RBC antibody generation. Humoral alloimmunization begins with consumption of transfused RBCs by antigen presenting cells (APCs). Recently, it has become appreciated that there are multiple different types of APCs. The relative contribution of APC subsets to RBC antibodies has not been described in either the quiescent or the inflamed states. STUDY DESIGN AND METHODS: To evaluate the types of APCs that consume RBCs, and how inflammation affects this process, C56Bl/6 mice were treated with polyinosinic-polycytidylic acid (poly(I:C)) to induce an inflammatory response and/or were transfused with 3,3'-dihexadecyloxacarbocyanine perchlorate-labeled syngeneic RBCs. Erythrophagocytosis (both at baseline and during inflammation) was analyzed for different subsets of macrophages (MPhi), dendritic cells (DCs), B cells, and monocytes, by a combined approach using flow cytometry and fluorescent microscopy technology. RESULTS: In four independent experiments, erythrophagocytosis at baseline was predominately performed by red pulp MPhi; however, during inflammation both plasmacytoid DCs (pDCs) and monocytes increased RBC consumption. Furthermore, pDCs up regulated MHC-II and activation markers CD80 and CD86. In addition to changing patterns of erythrophagocytosis, inflammation also led to a significant decrease in CD11c+ conventional DC populations and an increase in granulocytes. CONCLUSIONS: The nature of APCs that consume transfused RBCs is changed by inflammation. Given that APCs initiate humoral immune responses, these findings provide potential mechanistic insight into how inflammation regulates RBC alloimmunization. PMID- 26843480 TI - The Cost-Effectiveness of Real-Time Continuous Glucose Monitoring (RT-CGM) in Type 2 Diabetes. AB - BACKGROUND: This analysis models the cost-effectiveness of real-time continuous glucose monitoring (RT-CGM) using evidence from a randomized controlled trial (RCT) that demonstrated RT-CGM reduced A1C, for up to 9 months after using the technology, among patients with type 2 diabetes not on prandial insulin. RT-CGM was offered short-term and intermittently as a self-care tool to inform patients' behavior. METHOD: The analyses projected lifetime clinical and economic outcomes for RT-CGM versus self-monitoring of blood glucose by fingerstick only. The base case analysis was consistent with the RCT (RT-CGM for 2 weeks on/1 week off over 3 months). A scenario analysis simulated outcomes of an RT-CGM "refresher" after the active intervention of the RCT. Analyses used the IMS CORE Diabetes Model and were conducted from a US third-party payer perspective, including direct costs obtained from published sources and inflated to 2011 US dollars. Costs and health outcomes were discounted at 3% per annum. RESULTS: Life expectancy (LE) and quality-adjusted life expectancy (QALE) from RT-CGM were 0.10 and 0.07, with a cost of $653/patient over a lifetime. Incremental LE and QALE from a "refresher" were 0.14 and 0.10, with a cost of $1312/patient over a lifetime, and incremental cost-effectiveness ratios were $9319 and $13 030 per LY and QALY gained. CONCLUSIONS: RT-CGM, as a self-care tool, is a cost-effective disease management option in the US for people with type 2 diabetes not on prandial insulin. Repeated use of RT-CGM may result in additional cost-effectiveness. PMID- 26843481 TI - Treatment and survival of patients with insular thyroid carcinoma: 508 cases from the National Cancer Data Base. AB - BACKGROUND: Insular thyroid carcinoma (ITC) is a rare but aggressive thyroid malignancy. METHODS: Patients with ITC (n = 508) reported to the National Cancer Data Base from 1998 to 2012 were evaluated for patient, tumor, and treatment characteristics and outcomes. RESULTS: Compared to papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC), patients with ITC cancer were older, more often were men, had larger tumors, were more likely to present with distant metastasis, were less likely to have an R0 resection, more likely to receive external beam radiation and chemotherapy, and had significantly worse survival. Multivariate Cox regression identified age >65 years (hazard ratio [HR] = 1.53), presence of at least 1 comorbidity (HR = 1.80), positive lymph nodes (HR = 1.67), the presence of metastasis (HR = 2.73), positive margins (HR = 2.48), and radioactive iodine therapy (HR = 0.63) as significant and independent predictors of survival in ITC. CONCLUSION: Treatment recommendations should incorporate the use of radioactive iodine after complete surgical resection and clearance of involved nodal basins. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 906-912, 2016. PMID- 26843482 TI - Non-vitamin K antagonist oral anticoagulants and antiphospholipid syndrome. AB - The current treatment of thrombotic APS patients includes long-term anticoagulation with oral vitamin K antagonists (VKAs), with warfarin being the one most commonly used. However, the use of VKAs can be challenging, especially in patients with APS. VKAs monitoring in patients with aPL is complicated by the heterogeneous responsiveness to LAs of reagents used in the International Normalized Ratio test, potentially resulting in instability of anticoagulation. For decades, VKAs were the only available oral anticoagulants. However, non-VKA oral anticoagulants, including a direct thrombin inhibitor (dabigatran etexilate) and direct anti-Xa inhibitors (rivaroxaban, apixaban and edoxaban), are currently available. The use of these agents may represent a major step forward since, unlike VKAs, they have few reported drug interactions and they do not interact with food or alcohol intake, thereby resulting in more stable anticoagulant intensity. Most importantly, monitoring their anticoagulant intensity is not routinely required due to their predictable anticoagulant effects. In this review, we discuss the clinical and laboratory aspects of non-VKA oral anticoagulants, focusing on the available evidence regarding their use in patients with APS. PMID- 26843483 TI - An EULAR study group pilot study on reliability of simple capillaroscopic definitions to describe capillary morphology in rheumatic diseases. AB - OBJECTIVE: To propose simple capillaroscopic definitions for interpretation of capillaroscopic morphologies and to assess inter-rater reliability. METHODS: The simple definitions proposed were: normal--hairpin, tortuous or crossing; abnormal -not hairpin, not tortuous and not crossing; not evaluable--whenever rater undecided between normal and abnormal. Based upon an aimed kappa of 0.80 and default prevalences of normal (0.4), abnormal (0.4) and not evaluable (0.2) capillaries, 90 single capillaries were presented to three groups of raters: experienced independent raters, n = 5; attendees of the sixth EULAR capillaroscopy course, n = 34; novices after a 1-h course, n = 11. Inter-rater agreement was assessed by calculation of proportion of agreement and by kappa coefficients. RESULTS: Mean kappa based on 90 capillaries was 0.47 (95% CI: 0.39, 0.54) for expert raters, 0.40 (95% CI: 0.36, 0.44) for attendees and 0.46 (95% CI: 0.41, 0.52) for novices, with overall agreements of 67% (95% CI: 63, 71), 63% (95% CI: 60, 65) and 67% (95% CI: 63, 70), respectively. Comparing only normal vs the combined groups of abnormal and not evaluable capillaries did increase the kappa: 0.51 (95% CI: 0.37 ,: 0.65), 0.53 (95% CI: 0.49, 0.58) and 0.55 (95% CI: 0.49, 0.62). On the condition that the capillaries were classifiable, the mean kappa was 0.62 (95% CI: 0.50, 0.74) for expert raters (n = 65), 0.76 (95% CI: 0.69, 0.83) for attendees (n = 20) and 0.81 (95% CI: 0.74, 0.89) for novices (n = 44). CONCLUSION: This multicentre, international study showed moderate reliability of simple capillaroscopic definitions for describing morphology of capillaries by rheumatologists with varying levels of expertise. Novices were capable of distinguishing normal from abnormal capillaries by means of a 1-h training session. In future studies, the class not evaluable may be obsolete. PMID- 26843484 TI - Phase II multicenter study of gene-mediated cytotoxic immunotherapy as adjuvant to surgical resection for newly diagnosed malignant glioma. AB - BACKGROUND: Despite aggressive standard of care (SOC) treatment, survival of malignant gliomas remains very poor. This Phase II, prospective, matched controlled, multicenter trial was conducted to assess the safety and efficacy of aglatimagene besadenovec (AdV-tk) plus valacyclovir (gene-mediated cytotoxic immunotherapy [GMCI]) in combination with SOC for newly diagnosed malignant glioma patients. METHODS: Treatment cohort patients received SOC + GMCI and were enrolled at 4 institutions from 2006 to 2010. The preplanned, matched-control cohort included all concurrent patients meeting protocol criteria and SOC at a fifth institution. AdV-tk was administered at surgery followed by SOC radiation and temozolomide. Subset analyses were preplanned, based on prognostic factors: pathological diagnosis (glioblastoma vs others) and extent of resection. RESULTS: Forty-eight patients completed SOC + GMCI, and 134 met control cohort criteria. Median overall survival (OS) was 17.1 months for GMCI + SOC versus 13.5 months for SOC alone (P = .0417). Survival at 1, 2, and 3 years was 67%, 35%, and 19% versus 57%, 22%, and 8%, respectively. The greatest benefit was observed in gross total resection patients: median OS of 25 versus 16.9 months (P = .0492); 1, 2, and 3-year survival of 90%, 53%, and 32% versus 64%, 28% and 6%, respectively. There were no dose-limiting toxicities; fever, fatigue, and headache were the most common GMCI-related symptoms. CONCLUSIONS: GMCI can be safely combined with SOC in newly diagnosed malignant gliomas. Survival outcomes were most notably improved in patients with minimal residual disease after gross total resection. These data should help guide future immunotherapy studies and strongly support further evaluation of GMCI for malignant gliomas. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov NCT00589875. PMID- 26843485 TI - p38gamma and p38delta reprogram liver metabolism by modulating neutrophil infiltration. AB - Non-alcoholic fatty liver disease (NAFLD) is a major health problem and the main cause of liver disease in Western countries. Although NAFLD is strongly associated with obesity and insulin resistance, its pathogenesis remains poorly understood. The disease begins with an excessive accumulation of triglycerides in the liver, which stimulates an inflammatory response. Alternative p38 mitogen activated kinases (p38gamma and p38delta) have been shown to contribute to inflammation in different diseases. Here we demonstrate that p38delta is elevated in livers of obese patients with NAFLD and that mice lacking p38gamma/delta in myeloid cells are resistant to diet-induced fatty liver, hepatic triglyceride accumulation and glucose intolerance. This protective effect is due to defective migration of p38gamma/delta-deficient neutrophils to the damaged liver. We further show that neutrophil infiltration in wild-type mice contributes to steatosis development by means of inflammation and liver metabolic changes. Therefore, p38gamma and p38delta in myeloid cells provide a potential target for NAFLD therapy. PMID- 26843486 TI - The Secreted Protein Rv1860 of Mycobacterium tuberculosis Stimulates Human Polyfunctional CD8+ T Cells. AB - We previously reported that Rv1860 protein from Mycobacterium tuberculosis stimulated CD4(+)and CD8(+)T cells secreting gamma interferon (IFN-gamma) in healthy purified protein derivative (PPD)-positive individuals and protected guinea pigs immunized with a DNA vaccine and a recombinant poxvirus expressing Rv1860 from a challenge with virulent M. tuberculosis We now show Rv1860-specific polyfunctional T (PFT) cell responses in the blood of healthy latently M. tuberculosis-infected individuals dominated by CD8(+) T cells, using a panel of 32 overlapping peptides spanning the length of Rv1860. Multiple subsets of CD8(+) PFT cells were significantly more numerous in healthy latently infected volunteers (HV) than in tuberculosis (TB) patients (PAT). The responses of peripheral blood mononuclear cells (PBMC) from PAT to the peptides of Rv1860 were dominated by tumor necrosis factor alpha (TNF-alpha) and interleukin-10 (IL-10) secretions, the former coming predominantly from non-T cell sources. Notably, the pattern of the T cell response to Rv1860 was distinctly different from those of the widely studied M. tuberculosis antigens ESAT-6, CFP-10, Ag85A, and Ag85B, which elicited CD4(+) T cell-dominated responses as previously reported in other cohorts. We further identified a peptide spanning amino acids 21 to 39 of the Rv1860 protein with the potential to distinguish latent TB infection from disease due to its ability to stimulate differential cytokine signatures in HV and PAT. We suggest that a TB vaccine carrying these and other CD8(+) T-cell-stimulating antigens has the potential to prevent progression of latent M. tuberculosis infection to TB disease. PMID- 26843487 TI - Five-Antigen Fluorescent Bead-Based Assay for Diagnosis of Lyme Disease. AB - The systematically difficult task of diagnosing Lyme disease can be simplified by sensitive and specific laboratory tests. The currently recommended two-tier test for serology is highly specific but falls short in sensitivity, especially in the early acute phase. We previously examined serially collected serum samples from Borrelia burgdorferi-infected rhesus macaques and defined a combination of antigens that could be utilized for detection of infection at all phases of disease in humans. The five B. burgdorferi antigens, consisting of OspC, OspA, DbpA, OppA2, and the C6 peptide, were combined into a fluorescent cytometric bead based assay for the detection of B. burgdorferi antigen-specific IgG antibodies. Samples from Lyme disease patients and controls were used to determine the diagnostic value of this assay. Using this sample set, we found that our five antigen multiplex IgG assay exhibited higher sensitivity (79.5%) than the enzyme immunoassay (EIA) (76.1%), the two-tier test (61.4%), and the C6 peptide enzyme linked immunosorbent assay (ELISA) (77.2%) while maintaining specificity over 90%. When detection of IgM was added to the bead-based assay, the sensitivity improved to 91%, but at a cost of reduced specificity (78%). These results indicate that the rational combination of antigens in our multiplex assay may offer an improved serodiagnostic test for Lyme disease. PMID- 26843488 TI - RPGR-associated retinopathy: clinical features, molecular genetics, animal models and therapeutic options. AB - Retinitis pigmentosa GTPase regulator (RPGR) gene sequence variants account for the vast majority of X linked retinitis pigmentosa (RP), which is one of the most severe forms of RP. Symptoms of nyctalopia typically begin in childhood, with increasing loss of peripheral visual field during teenage years, and progressive central visual loss during the second to fourth decade of life. There is however marked intrafamilial and interfamilial phenotypic heterogeneity in affected males and carrier females. There is now a far greater understanding of the range of phenotypes associated with variants in this gene; including rod-cone dystrophy, cone-rod dystrophy, cone dystrophy, macular dystrophy and non-ocular phenotypes. There are also increasingly established genotype-phenotype associations and structure-function correlations. RPGR is involved in ciliary function, with ciliary dysfunction now recognised as the mechanism underlying a large proportion of inherited retinal disease. There has been significant progress in identifying naturally occurring animal models and developing novel models to define the underlying disease mechanisms and to test gene replacement therapy, in addition to advances in human retinal imaging, culminating in completed and planned clinical trials. These significant developments will be discussed. PMID- 26843489 TI - Mutations in EXOSC2 are associated with a novel syndrome characterised by retinitis pigmentosa, progressive hearing loss, premature ageing, short stature, mild intellectual disability and distinctive gestalt. AB - BACKGROUND: Retinitis pigmentosa in combination with hearing loss can be a feature of different Mendelian disorders. We describe a novel syndrome caused by biallelic mutations in the 'exosome component 2' (EXOSC2) gene. METHODS: Clinical ascertainment of three similar affected patients followed by whole exome sequencing. RESULTS: Three individuals from two unrelated German families presented with a novel Mendelian disorder encompassing childhood myopia, early onset retinitis pigmentosa, progressive sensorineural hearing loss, hypothyroidism, short stature, brachydactyly, recognisable facial gestalt, premature ageing and mild intellectual disability. Whole exome sequencing revealed homozygous or compound heterozygous missense variants in the EXOSC2 gene in all three patients. EXOSC2 encodes the 'ribosomal RNA-processing protein 4' (RRP4)-one of the core components of the RNA exosome. The RNA exosome is a multiprotein complex that plays key roles in RNA processing and degradation. Intriguingly, the EXOSC2-associated phenotype shows only minimal overlap with the previously reported diseases associated with mutations in the RNA exosome core component genes EXOSC3 and EXOSC8. CONCLUSION: We report a novel condition that is probably caused by altered RNA exosome function and expands the spectrum of clinical consequences of impaired RNA metabolism. PMID- 26843491 TI - Hospital pharmacies cope with surge in drug prices. PMID- 26843490 TI - Salt Intakes, Knowledge, and Behavior in Samoa: Monitoring Salt-Consumption Patterns Through the World Health Organization's Surveillance of Noncommunicable Disease Risk Factors (STEPS). AB - This project measured population salt intake in Samoa by integrating urinary sodium analysis into the World Health Organization's (WHO's) STEPwise approach to surveillance of noncommunicable disease risk factors (STEPS). A subsample of the Samoan Ministry of Health's 2013 STEPS Survey collected 24-hour and spot urine samples and completed questions on salt-related behaviors. Complete urine samples were available for 293 participants. Overall, weighted mean population 24-hour urine excretion of salt was 7.09 g (standard error 0.19) to 7.63 g (standard error 0.27) for men and 6.39 g (standard error 0.14) for women (P=.0014). Salt intake increased with body mass index (P=.0004), and people who added salt at the table had 1.5 g higher salt intakes than those who did not add salt (P=.0422). A total of 70% of the population had urinary excretion values above the 5 g/d cutoff recommended by the WHO. A reduction of 30% (2 g) would reduce average population salt intake to 5 g/d, in line with WHO recommendations. While challenging, integration of salt monitoring into STEPS provides clear logistical and cost benefits and the lessons communicated here can help inform future programs. PMID- 26843492 TI - Standards on handling hazardous drugs set for release. PMID- 26843494 TI - Medication safety pharmacy technician in a large, tertiary care, community hospital. PMID- 26843495 TI - Pembrolizumab and nivolumab: PD-1 inhibitors for advanced melanoma. AB - PURPOSE: The immunology of programmed cell death protein 1 (PD-1) inhibitors, as well as the clinical efficacy of pembrolizumab and nivolumab in the treatment of metastatic melanoma, is reviewed. SUMMARY: PD-1 inhibitors pembrolizumab and nivolumab are novel immunotherapies that were recently approved by the Food and Drug Administration for the treatment of unresectable or metastatic melanoma in treatment-refractory patients. Pembrolizumab and nivolumab are monoclonal antibodies that bind to the PD-1 receptor and prevent its interaction with its ligands programmed cell death receptor ligands 1 and 2. Inhibition of the PD-1 receptor allows for increased immune response and potentially increased anticancer immune activity. Clinical trials with pembrolizumab and nivolumab in patients with unresectable melanoma refractory to ipilimumab or targeted agents demonstrated objective response rates of 26-38% and 31-40%, respectively, and acceptable toxicity profiles. While most patients experienced some form of treatment-related adverse event, most of these effects were mild (grade 1 or 2) and were managed with treatment interruption or supportive care. Pembrolizumab is administered via continuous i.v. infusion over 30 minutes at a dose of 2 mg/kg of actual body weight every three weeks. Nivolumab is administered as a continuous i.v. infusion over 60 minutes. The recommended dose of nivolumab is 3 mg/kg of actual body weight administered every two weeks until disease progression or the development of intolerable toxicities. CONCLUSION: Pembrolizumab and nivolumab monotherapies are effective therapies in ipilimumab-refractory metastatic melanoma and present an overall favorable toxicity profile. PMID- 26843496 TI - Treatment of hemorrhagic acute disseminated encephalomyelitis with cyclophosphamide. AB - PURPOSE: Improvements in hemorrhagic and clinical symptoms in a patient with hemorrhagic acute disseminated encephalomyelitis (ADEM) treated with i.v. cyclophosphamide are reported. SUMMARY: A 49-year-old woman was hospitalized with progressively worsening left-sided weakness, dysphagia, diplopia, and vertigo. Shortly before hospital admission, the patient had been treated at another facility with corticosteroids and plasma exchanges. Brain magnetic resonance imaging (MRI) studies conducted at the time of admission showed demyelinating lesions of the pons consistent with ADEM; rapid progression of the patient's symptoms also suggested an autoimmune, demyelinating process, and viral studies ruled out an infectious etiology. Despite initial treatment with i.v. immune globulin and additional corticosteroid courses, the patient's condition continued to deteriorate over the next few weeks, with development of respiratory distress requiring intubation. Repeat MRI revealed a new brain lesion in the splenial region of the corpus callosum, prompting the initiation of i.v. cyclophosphamide therapy (180 mg daily). Approximately 19 days after cyclophosphamide therapy was initiated, an MRI scan revealed substantial reduction of the pontine hemorrhage and a normal splenium appearance, with no new lesion development. The use of cyclophosphamide for hemorrhagic ADEM refractory to other treatments has been previously reported. CONCLUSION: After approximately three weeks of daily i.v. cyclophosphamide therapy, a patient with hemorrhagic ADEM was noted to have stable to improved brain MRI findings along with limited improvement of mental status and movement symptoms. PMID- 26843497 TI - Predictive performance of glomerular filtration rate estimation equations based on cystatin C versus serum creatinine values in critically ill patients. AB - PURPOSE: The predictive performance of glomerular filtration rate (GFR) estimation equations based on cystatin C versus serum creatinine (SCr) values in critically ill patients was evaluated. METHODS: A retrospective observational study was performed in the medical intensive care unit (ICU) of a university hospital from October 2006 through September 2007. All consecutively admitted critically ill patients older than 18 years who stayed in the ICU for more than 48 hours with a urinary bladder catheter in place were included in the study. Data collected included SCr, cystatin C, serum albumin, blood urea nitrogen, and 24-hour urine creatinine clearance [Formula: see text] levels. The following equations were also used to determine the estimated GFR that was compared with the reference [Formula: see text] for all patients in the study: Arnal-Dade using cystatin C, Cockcroft-Gault using actual body weight, Cockcroft-Gault using ideal body weight, Jelliffe, Modification of Diet in Renal Disease (MDRD), and four variable version MDRD (MDRD-4). RESULTS: This study included 241 measurements corresponding to 131 critically ill patients. The cystatin C-based equation underestimated [Formula: see text], whereas overestimation by every SCr-based formula was observed in the whole cohort and in the [Formula: see text] subgroup; MDRD-4 was the most biased equation in every analysis. There were no significant differences in precision, except for great variability in the subgroup with a [Formula: see text] of <60 mL/min/1.73 m(2), where the MDRD equation showed better results than the cystatin C-based equation (33.5% versus 38.9%). No equations fulfilled concordance requirements with [Formula: see text]. CONCLUSION: A retrospective observational study showed no evidence of superiority of a cystatin C-based equation over SCr-based equations to estimate the GFR in an ICU population. PMID- 26843498 TI - Comparison of a pharmacist-hospitalist collaborative model of inpatient care with multidisciplinary rounds in achieving quality measures. AB - PURPOSE: Results of a study of hospitalization outcomes with the use of a pharmacist-hospitalist collaborative (PHC) model of care as an alternative to multidisciplinary rounds (MDR) are reported. METHODS: In a retrospective matched cohort study, data on more than 2000 adults discharged from two medical units of a community teaching hospital were analyzed to compare selected outcomes before and after the units augmented traditional hospitalist care (usual care) with either MDR or a PHC care model emphasizing pharmacist involvement in case review and medication management. The study cohorts were matched for primary diagnosis, severity of illness, and other variables. The outcomes were mean length of stay (LOS) and rates of all-cause readmission during designated preintervention and intervention periods. RESULTS: Among patients admitted to the unit that implemented the PHC care model, those admitted during the preintervention period had a longer mean LOS than matched intervention-phase patients: 5.5 days (95% confidence interval [CI], 5.0-6.0 days) versus 4.7 days (95% CI, 4.2-5.3 days); p = 0.002. Patients admitted to the MDR unit during the preintervention period also had a significantly longer mean LOS than those in the matched intervention-phase cohort. There were no significant between-group differences in all-cause readmissions. CONCLUSION: Systematic implementation of either the PHC or the MDR model of care was associated with a decreased mean hospital LOS relative to LOS values with usual care only. No significant differences in readmissions at 30, 60, and 90 days were attributable to implementation of the PHC or the MDR model. PMID- 26843499 TI - Outcomes of annual wellness visits provided by pharmacists in an accountable care organization associated with a federally qualified health center. AB - BACKGROUND: The clinical and financial outcomes of annual wellness visits (AWVs) conducted by clinical pharmacists working as part of an accountable care organization (ACO) in a federally qualified health center were evaluated. METHODS: In this retrospective, single-center, chart review study, patients seen for AWVs at El Rio Health Center between October and December 2013 were eligible for study inclusion. Data collected from patient charts included patient demographics, preventive screenings ordered by clinical pharmacists during the AWV and completed within one month after the visit, other screenings completed by clinical pharmacists during the visit, medication changes by clinical pharmacists, and revenues collected from the AWV and preventive screenings. Descriptive statistics were calculated and variables compared; p values were calculated using single-sample Student's t tests. RESULTS: Three hundred patient records were reviewed. Clinical pharmacists completed 1608 interventions, with a mean of 5.4 interventions per patient. A total of 272 referrals were made, 120 (45%) of which were completed within one month of the visit. Of the 183 laboratory tests ordered for diabetes and lipid screening, 152 (83%) were completed within one month of the AWV (p < 0.001). Of the 370 vaccinations offered during the visits, 182 (49%) were administered (p < 0.001). Twenty-four medication and dosage changes were made by clinical pharmacists during AWVs, and the total revenue for the AWVs conducted by pharmacists and services completed during the visits exceeded $22,000. CONCLUSION: Recommendations made by pharmacists during AWVs in an ACO associated with a federally qualified health center had a high acceptance rate and generated substantial revenue. PMID- 26843500 TI - Geriatric pharmacy training requirements: A survey of residency programs. AB - PURPOSE: Results of a survey assessing opportunities for geriatrics training currently available to pharmacy residents and residency directors' views on the concept of a defined slate of required geriatrics rotations are reported. METHODS: Directors of postgraduate year 1 (PGY1) pharmacy residency programs (n = 368) and postgraduate year 2 (PGY2) geriatric pharmacy residencies (n = 13) were surveyed regarding current training opportunities in geriatrics. PGY2 residency directors were invited to participate in a follow-up survey to identify high priority areas for possible standardization of residency requirements on clinical rotations in geriatric practice settings. RESULTS: About 21% of the PGY1 residency directors who responded to the survey indicated that their program required a geriatrics rotation, and 47% reported elective geriatrics rotations. All 13 PGY2 geriatric pharmacy residencies represented in the survey offered a long-term care rotation, with 12 offering rotations in mental health and outpatient geriatrics, 11 offering a hospice/palliative care rotation, and 10 offering a rotation in inpatient geriatrics. All 11 PGY2 directors who responded to the follow-up survey supported requiring a long-term care rotation in future revisions of the ASHP accreditation standard for geriatric pharmacy residencies; 10 supported required rotations in inpatient and outpatient geriatrics, and 9 supported requiring a hospice/palliative care rotation. CONCLUSION: Geriatrics oriented training in PGY1 pharmacy residencies is limited, with only about one in five programs requiring a geriatrics rotation. The survey results indicated broad support among PGY2 program heads for required rotations in various geriatric healthcare settings. PMID- 26843501 TI - Characteristics of FDA drug recalls: A 30-month analysis. AB - PURPOSE: The characteristics of drug recalls issued over 30 months by the Food and Drug Administration (FDA) were analyzed. METHODS: All FDA-issued recalls for drugs (prescription and nonprescription, including dietary supplements) and biological products issued from June 20, 2012, to December 31, 2014, were included in this retrospective analysis. Data for all drug recalls were downloaded and sorted by the inclusion criteria from weekly FDA enforcement reports. The following data were analyzed: product type, recall firm, type of recall firm (compounding or noncompounding), country, voluntary or involuntary recall, method of communication of recall, recall number, FDA recall classification (class I, II, or III), product availability (prescription or nonprescription), reason for recall, recall initiation date, and recall report date. RESULTS: A total of 21,120 products were recalled during the 30-month study period. Of these, 3,045 drug products (14.4%) met the inclusion criteria and were analyzed. A total of 348 total manufacturers were associated with recalled drug products. The 5 firms most frequently involved in recalls accounted for 299, 273, 212, 118, and 112 recalls. The most common reasons for recalls were contamination, mislabeling, adverse reaction, defective product, and incorrect potency. There was a significant association between FDA recall classification and the following outcomes: reasons for recall, product availability, type of recall firm, and form of communication. CONCLUSION: An investigation of FDA drug recalls revealed that the five most common recall reasons were contamination, mislabeling, adverse reaction, defective product, and incorrect potency. Compounding firms were associated more frequently with contamination than were noncompounding firms. PMID- 26843503 TI - ASHP Multihospital Health-System Pharmacy Executives Leadership Symposium: Forecasting the future of pharmacy: A five-year plan October 19, 2014. PMID- 26843502 TI - Visual and absorbance analyses of admixtures containing vancomycin and piperacillin-tazobactam at commonly used concentrations. AB - PURPOSE: The compatibility of vancomycin and piperacillin-tazobactam in concentrations typically used in extended-infusion dosing schemes was evaluated. METHODS: Piperacillin-tazobactam was reconstituted and diluted to concentrations of 33.75, 45, 50, 60, 67.5, 80, and 90 mg/mL. Vancomycin was diluted to concentrations of 4-8, 10, and 12 mg/mL. The resultant admixtures were visually observed after preparation against black and white backgrounds each hour between hours 1 through 4 and after 24 hours. Frozen products of each medication and brand-name Zosyn powder for reconstitution also were studied. Each combination of products and concentrations was tested for precipitation using simulated Y-site administration. Absorbance and microscopic analyses were performed to discern less perceptible incompatibilities in combinations that did not result in visual precipitation. Changes in absorbance were evaluated using two-way repeated measures analysis of variance with post hoc Bonferroni corrections. RESULTS: No tested concentrations of piperacillin-tazobactam showed precipitations with vancomycin up to concentrations of 7 mg/mL. Piperacillin-tazobactam 80-90 mg/mL formed reversible precipitation with vancomycin 8 mg/mL. All tested concentrations of piperacillin-tazobactam formed a reversible precipitate with vancomycin 10 mg/mL. Irreversible precipitation was noted with all combinations of piperacillin-tazobactam and vancomycin 12 mg/mL. No significant changes in absorbance analyses were identified for all tested piperacillin-tazobactam concentrations and vancomycin 4-10 mg/mL compared with 0.9% sodium chloride injection (p > 0.05). Similar results were observed using frozen preparations and brand-name Zosyn. CONCLUSION: Visual, microscopic, and absorbance analyses showed no evidence of incompatibility when piperacillin-tazobactam 33.75-90 mg/mL was combined with vancomycin <=7 mg/mL. Reversible and irreversible precipitates formed when piperacillin-tazobactam was combined with vancomycin >=8 mg/mL. PMID- 26843504 TI - Professional Policies Approved by the 2015 ASHP Virtual House of Delegates. PMID- 26843506 TI - Correspondence to: Morphological features in eyes with endophthalmitis after cataract surgery - histopathology and optical coherence tomography assessment by Yolcy et al. PMID- 26843505 TI - Do extra-articular manifestations influence outcome in ankylosing spondylitis? 12 year results from OASIS. AB - OBJECTIVES: To assess in patients with ankylosing spondylitis (AS) whether extra articular manifestations (EAMs) are associated with worse functioning, worse quality of life (QoL), and more radiographic damage over time. METHODS: 12-year follow-up data from the Outcome in Ankylosing Spondylitis International Study were used, complemented with data on EAMs extracted from medical charts. Functioning was assessed by the BASFI and physical component of the SF-36, QoL by ASQoL and EuroQoL, and radiographic damage by the mSASSS. Generalised estimating equations analyses were made to assess whether EAMs were associated with these outcomes over time. RESULTS: 216 patients were included (154 (71%) men, mean age 43.6 years (SD 12.7), mean symptom duration 20.5 years (SD 11.7), and mean follow up 8.3 years (SD 4.3). In total, 58 (26.9%) patients had acute anterior uveitis (AAU), 24 (11.1%) inflammatory bowel disease (IBD), and 14 (6.5%) psoriasis. Univariably, IBD was associated with worse BASFI over time (B=1.26, 95%-CI 0.13 to 2.39, p=0.03), but not in a multivariable model. Furthermore, in a multivariable model, IBD was associated with EuroQoL over time (B=2.93, 95%-CI 0.14 to 5.72, p=0.04). Univariably, psoriasis was associated with radiographic damage (B=-7.25, 95%-CI -14.38 to -0.12, p=0.05) and ASQoL (B= -1.94, 95%-CI 3.32 to -0.57, p<0.01) over time, but not in a multivariable model. AAU was not associated with any outcome over time. CONCLUSIONS: In this longstanding AS cohort, the presence of EAMs was not associated with functional disability, QoL or radiographic damage over time, except for IBD, which was associated with a better EuroQoL. PMID- 26843507 TI - Rituximab improved systemic lupus erythematosus-associated pulmonary alveolar proteinosis without decreasing anti-GM-CSF antibody levels. PMID- 26843509 TI - Dose-dependent fate of GFP-expressing Escherichia coli in the alimentary canal of adult house flies. AB - The adult house fly Musca domestica (L.) (Diptera: Muscidae) can disseminate bacteria from microbe-rich substrates to areas in which humans and domesticated animals reside. Because bacterial abundance fluctuates widely across substrates, flies encounter and ingest varying amounts of bacteria. This study investigated the dose-dependent survival of bacteria in house flies. Flies were fed four different 'doses' of green fluorescent protein (GFP)-expressing Escherichia coli (GFP E. coli) (very low, low, medium, high) and survival was determined at 1, 4, 10 and 22 h post-ingestion by culture and epifluorescent microscopy. Over 22 h, the decline in GFP E. coli was significant in all treatments (P < 0.04) except the very low dose treatment (P = 0.235). Change in survival (DeltaS) did not differ between flies fed low and very low doses of bacteria across all time points, although DeltaS in both treatments differed from that in flies fed high and medium doses of bacteria at several time-points. At 4, 10 and 22 h, GFP E. coli DeltaS significantly differed between medium and high dose-fed flies. A threshold dose, above which bacteria are detected and destroyed by house flies, may exist and is likely to be immune-mediated. Understanding dose-dependent bacterial survival in flies can help in predicting bacteria transmission potential. PMID- 26843508 TI - Fungal microbiota dysbiosis in IBD. AB - OBJECTIVE: The bacterial intestinal microbiota plays major roles in human physiology and IBDs. Although some data suggest a role of the fungal microbiota in IBD pathogenesis, the available data are scarce. The aim of our study was to characterise the faecal fungal microbiota in patients with IBD. DESIGN: Bacterial and fungal composition of the faecal microbiota of 235 patients with IBD and 38 healthy subjects (HS) was determined using 16S and ITS2 sequencing, respectively. The obtained sequences were analysed using the Qiime pipeline to assess composition and diversity. Bacterial and fungal taxa associated with clinical parameters were identified using multivariate association with linear models. Correlation between bacterial and fungal microbiota was investigated using Spearman's test and distance correlation. RESULTS: We observed that fungal microbiota is skewed in IBD, with an increased Basidiomycota/Ascomycota ratio, a decreased proportion of Saccharomyces cerevisiae and an increased proportion of Candida albicans compared with HS. We also identified disease-specific alterations in diversity, indicating that a Crohn's disease-specific gut environment may favour fungi at the expense of bacteria. The concomitant analysis of bacterial and fungal microbiota showed a dense and homogenous correlation network in HS but a dramatically unbalanced network in IBD, suggesting the existence of disease-specific inter-kingdom alterations. CONCLUSIONS: Besides bacterial dysbiosis, our study identifies a distinct fungal microbiota dysbiosis in IBD characterised by alterations in biodiversity and composition. Moreover, we unravel here disease-specific inter-kingdom network alterations in IBD, suggesting that, beyond bacteria, fungi might also play a role in IBD pathogenesis. PMID- 26843511 TI - Role of E-selectin for diagnosing myocardial injury in paediatric patients with mycoplasma pneumoniae pneumonia. AB - Backgrounds Effects of myocardial injury on E-selectin remain unclear. Thus, we investigated the diagnostic value of E-selectin for myocardial injury in paediatric patients with mycoplasma pneumoniae pneumonia. Methods In this prospective and blinded clinical study, plasma E-selectin, cardiac troponin I, creatine kinase isoenzyme MB, interleukin-6 and tumor necrosis factor alpha concentrations were measured in paediatric patients with mycoplasma pneumoniae pneumonia (MPP group, n = 138). The control group comprised 120 healthy children. The definition of cardiac injury was based on cardiac troponin I or CK-MB (with or possibly without abnormal electrocardiogram evidence). Diagnostic value of E selectin for myocardial injury was determined by analysing receiver operating characteristic curves. Results Among the 138 mycoplasma pneumoniae pneumonia patients, 40 patients were identified with myocardial injury, while 98 patients were identified without myocardial injury. Plasma E-selectin concentrations were: 40.22 +/- 4.80 ng/mL, in patients with myocardial injury; 18.55 +/- 2.16 ng/mL, in patients without myocardial injury and 12.39 +/- 3.27 ng/mL, in healthy children. For the 40 patients identified with myocardial injury, area under the receiver operating characteristic curve value for plasma E-selectin concentrations was 0.945 (95% CI: 0.899-0.991), and optimal diagnostic cut-off value was 29.93 ng/mL (positive likelihood ratio = 72.5). Conclusion E-selectin was shown to be an effective index for myocardial injury in paediatric patients with mycoplasma pneumoniae pneumonia, and its role in other causes of myocardial injury warrants further investigation. PMID- 26843510 TI - Pathways between stigma and suicidal ideation among people at risk of psychosis. AB - Mental illness stigma may contribute to suicidality and is associated with social isolation and low self-esteem among young people at risk of psychosis. However, it is unclear whether mental illness stigma contributes to suicidality in this population. We therefore examined the associations of self-labeling and stigma stress with suicidality among young people at risk. Self-labeling as "mentally ill", stigma stress, social isolation, self-esteem, symptoms and suicidal ideation were assessed in 172 individuals at risk of psychosis. Self-labeling and stigma stress were examined as predictors of suicidality by path analysis. Increased self-labeling as "mentally ill" was associated with suicidality, directly as well as indirectly mediated by social isolation. More stigma stress was related to social isolation which in turn was associated with low self esteem, depression and suicidal ideation. Social isolation fully mediated the link between stigma stress and suicidal ideation. Interventions to reduce the public stigma associated with risk of psychosis as well as programs to facilitate non-stigmatizing awareness of at-risk mental state and to reduce stigma stress among young people at risk of psychosis might strengthen suicide prevention in this population. PMID- 26843512 TI - Combination of modified mixing technique and low frequency ultrasound to control the elution profile of vancomycin-loaded acrylic bone cement. AB - OBJECTIVES: The objective of this study was to determine if combining variations in mixing technique of antibiotic-impregnated polymethylmethacrylate (PMMA) cement with low frequency ultrasound (LFUS) improves antibiotic elution during the initial high phase (Phase I) and subsequent low phase (Phase II) while not diminishing mechanical strength. METHODS: Three batches of vancomycin-loaded PMMA were prepared with different mixing techniques: a standard technique; a delayed technique; and a control without antibiotic. Daily elution samples were analysed using flow injection analysis (FIA). Beginning in Phase II, samples from each mix group were selected randomly to undergo either five, 15, 45, or 0 minutes of LFUS treatment. Elution amounts between LFUS treatments were analysed. Following Phase II, compression testing was done to quantify strength. A-priori t-tests and univariate ANOVAs were used to compare elution and mechanical test results between the two mix groups and the control group. RESULTS: The delayed technique showed a significant increase in elution on day one compared with the standard mix technique (p < 0.001). The transition point from Phase I to Phase II occurred on day ten. LFUS treatments significantly increased elution amounts for all groups above control. Delayed technique resulted in significantly higher elution amounts for the five-minute- (p = 0.004) and 45-minute- (p < 0.001) duration groups compared with standard technique. Additionally, the correlations between LFUS duration and total elution amount for both mix techniques were significant (p = 0.03). Both antibiotic-impregnated groups exhibited a significant decrease in offset yield stress compared with the control group (p < 0.001), however, their lower 95% confidence intervals were all above the 70 MPa limit defined by International Standards Organization (ISO) 5833-2 reference standard for acrylic bone cement. CONCLUSION: The combination of a delayed mix technique with LFUS treatments provides a reasonable means for increasing both short- and long-term antibiotic elution without affecting mechanical strength.Cite this article: Dr. T. McIff. Combination of modified mixing technique and low frequency ultrasound to control the elution profile of vancomycin-loaded acrylic bone cement. Bone Joint Res 2016;5:26-32. doi: 10.1302/2046-3758.52.2000412. PMID- 26843514 TI - Identification of the novel HLA-B*07:261 allele. PMID- 26843515 TI - The relationship between non-communicable disease occurrence and poverty-evidence from demographic surveillance in Matlab, Bangladesh. AB - In low-income countries, a growing proportion of the disease burden is attributable to non-communicable diseases (NCDs). There is little knowledge, however, of their impact on wealth, human capital, economic growth or household poverty. This article estimates the risk of being poor after an NCD death in the rural, low-income area of Matlab, Bangladesh. In a matched cohort study, we estimated the 2-year relative risk (RR) of being poor in Matlab households with an NCD death in 2010. Three separate measures of household economic status were used as outcomes: an asset-based index, self-rated household economic condition and total household landholding. Several estimation methods were used including contingency tables, log-binomial regression and regression standardization and machine learning. Households with an NCD death had a large and significant risk of being poor. The unadjusted RR of being poor after death was 1.19, 1.14 and 1.10 for the asset quintile, self-rated condition and landholding outcomes. Adjusting for household and individual level independent variables with log binomial regression gave RRs of 1.19 [standard error (SE) 0.09], 1.16 (SE 0.07) and 1.14 (SE 0.06), which were found to be exactly the same using regression standardization (SE: 0.09, 0.05, 0.03). Machine learning-based standardization produced slightly smaller RRs though still in the same order of magnitude. The findings show that efforts to address the burden of NCD may also combat household poverty and provide a return beyond improved health. Future work should attempt to disentangle the mechanisms through which economic impacts from an NCD death occur. PMID- 26843516 TI - Three-dimensional digital cast analysis of the effects produced by a passive self ligating system. AB - AIM: To evaluate maxillary and mandibular dental arch changes induced by a passive self-ligating system by analysing digital dental casts. SUBJECTS AND METHODS: A sample of 25 growing patients (16 females and 9 males, mean age 12.8 years) treated with passive self-ligating brackets was compared to a sample of 25 untreated controls (15 females and 10 males, mean age 13.4 years). Sixty three dimensional points were digitised on the maxillary and mandibular pre- and post treatment virtual models to evaluate differences in the transverse and antero posterior arch dimensions and in the torque values of representative anterior and posterior teeth. Statistical comparisons were performed with independent sample t tests with Holm-Bonferroni correction for multiple tests. RESULTS: The greatest increments in arch widths were found at the maxillary and mandibular premolar level (ranging from 2.0 to 2.2mm) and they were associated with significant increases in maxillary and mandibular arch perimeters (2.3 and 2.5mm, respectively), and in buccal crown torque of the upper premolars (with adequate torque control of all other teeth). CONCLUSIONS: The passive self-ligating system produced a modest but statistically significant widening of both maxillary and mandibular dental arches that were associated with significant net gains in maxillary and mandibular arch perimeters. PMID- 26843517 TI - Cytoskeletal architecture and cell motility remain unperturbed in mouse embryonic fibroblasts from Plk3 knockout mice. AB - Polo-like kinase 3 (Plk3) is best known for its involvement in cell cycle checkpoint regulation following exposure to cytotoxicants or induction of DNA damage. Yet, Plk3 has also been implicated in roles beyond those of cellular responses to DNA damage. Here, we have investigated the proposition, suggested by the Plk literature, that Plk3 regulates cytoskeletal architecture and cell functions mediated by the cytoskeleton. To this end, we have assayed mouse embryonic fibroblasts (MEFs) generated from both Plk3 knockout and wild-type mice. In particular, we asked whether Plk3 is involved in actin fiber and microtubule integrity, cell migration, cell attachment, and/or cell invasion. Our results demonstrate that functional Plk3 is not critical for the regulation of cytoskeletal integrity, cell morphology, cell adhesion, or motility in MEFs. PMID- 26843513 TI - Hypothesis: solid tumours behave as systemic metabolic dictators. AB - Current knowledge regarding mechanisms of carcinogenesis in human beings centres around the accumulation of genetic instability, amplified cellular signalling, disturbed cellular energy metabolism and microenvironmental regulation governed by complicated cell-cell interactions. In this article, we provide an alternative view of cancer biology. We propose that cancer behaves as a systemic dictator that interacts with tissues throughout the body to control their metabolism and eventually homeostasis. The mechanism of development of this endocrine organ-like tumour (EOLT) tissue might be the driving force for cancer progression. Here, we review the literature that led to the development of this hypothesis. The EOLT phenotype can be defined as a tumour that alters systemic homeostasis. The literature indicates that the EOLT phenotype is present throughout cancer progression. The feedback mechanism that governs the interaction between tumours and various organs is unknown. We believe that investigating the mechanism of EOLT development may advance the current knowledge of regulation within the tumour macroenvironment and consequently lead to new diagnostic methods and therapy. PMID- 26843519 TI - Epithelial discrimination of commensal and pathogenic Candida albicans. AB - All mucosal surfaces are lined by epithelial cells and are colonised by opportunistic microbes. In health, these opportunistic microbes remain commensal and are tolerated by the immune system. However, when the correct environmental conditions arise, these microbes can become pathogenic and need to be controlled or cleared by the immune system to prevent disease. The mechanisms that enable epithelial cells to initiate the 'danger' signals activated specifically by pathogenic microbes are critical to mucosal defence and homeostasis but are not well understood. Deciphering these mechanisms will provide essential understanding to how mucosal tissues maintain health and activate immunity, as well as how pathogens promote disease. This review focuses on the interaction of the human fungal pathogen Candida albicans with epithelial cells and the epithelial mechanisms that enable mucosal tissues to discriminate between the commensal and pathogenic state of this medically important fungus. PMID- 26843518 TI - Tantalum coating of porous carbon scaffold supplemented with autologous bone marrow stromal stem cells for bone regeneration in vitro and in vivo. AB - Porous tantalum metal with low elastic modulus is similar to cancellous bone. Reticulated vitreous carbon (RVC) can provide three-dimensional pore structure and serves as the ideal scaffold of tantalum coating. In this study, the biocompatibility of domestic porous tantalum was first successfully tested with bone marrow stromal stem cells (BMSCs) in vitro and for bone tissue repair in vivo. We evaluated cytotoxicity of RVC scaffold and tantalum coating using BMSCs. The morphology, adhesion, and proliferation of BMSCs were observed via laser scanning confocal microscope and scanning electron microscopy. In addition, porous tantalum rods with or without autologous BMSCs were implanted on hind legs in dogs, respectively. The osteogenic potential was observed by hard tissue slice examination. At three weeks and six weeks following implantation, new osteoblasts and new bone were observed at the tantalum-host bone interface and pores. At 12 weeks postporous tantalum with autologous BMSCs implantation, regenerated trabecular equivalent to mature bone was found in the pore of tantalum rods. Our results suggested that domestic porous tantalum had excellent biocompatibility and could promote new bone formation in vivo. Meanwhile, the osteogenesis of porous tantalum associated with autologous BMSCs was more excellent than only tantalum implantation. Future clinical studies are warranted to verify the clinical efficacy of combined implantation of this domestic porous tantalum associated with autologous BMSCs implantation and compare their efficacy with conventional autologous bone grafting carrying blood vessel in patients needing bone repairing. PMID- 26843521 TI - A Comprehensive Meta-analysis of Case-Control Association Studies to Evaluate Polymorphisms Associated with the Risk of Differentiated Thyroid Carcinoma. AB - BACKGROUND: Linkage analyses and association studies suggested that inherited genetic variations play a role in the development of differentiated thyroid carcinoma (DTC). METHODS: We combined the results from a genome-wide association study (GWAS) performed by our group and from published studies on DTC. With a first approach, we evaluated whether a SNP published as associated with the risk of DTC could replicate in our GWAS (using FDR as adjustment for multiple comparisons). With the second approach, meta-analyses were performed between literature and GWAS when both sources suggested an association, increasing the statistical power of the analysis. RESULTS: rs1799814 (CYP1A1), rs1121980 (FTO), and 3 SNPs within 9q22 (rs965513, rs7048394, and rs894673) replicated the associations described in the literature. In addition, the meta-analyses between literature and GWAS revealed 10 more SNPs within 9q22, six within FTO, two within SOD1, and single variations within HUS1, WDR3, UGT2B7, ALOX12, TICAM1, ATG16L1, HDAC4, PIK3CA, SULF1, IL11RA, VEGFA, and 1p31.3, 2q35, 8p12, and 14q13. CONCLUSION: This analysis confirmed several published risk loci that could be involved in DTC predisposition. IMPACT: These findings provide evidence for the role of germline variants in DTC etiology and are consistent with a polygenic model of the disease. Cancer Epidemiol Biomarkers Prev; 25(4); 700-13. (c)2016 AACR. PMID- 26843522 TI - Possible Selves and Self-Regulatory Beliefs: Exploring the Relationship Between Health Selves, Health Efficacy, and Psychological Well-Being. AB - The present study identified middle-aged (ages 40-64) and older individuals (ages 65-90) who reported a highly important possible self related to health. The relationship between age, physical health, health efficacy, and psychological well-being were examined among these individuals. We tested a model in which health efficacy predicted both positive and negative psychological well-being. For both age groups, self-reported health predicted health self-efficacy; however, the direct effects of health efficacy on both positive and negative psychological well-being were also significant. Higher levels of health efficacy were associated with higher levels of positive psychological well-being and lower levels of negative well-being, as predicted. Physical health indirectly predicted well-being through its impact on health self-efficacy for middle-aged and older individuals who valued their health highly. Overall, these results support the notion that health efficacy related to a most important health self is a predictor of psychological well-being in mid and late life. PMID- 26843520 TI - Time to Colonoscopy after Positive Fecal Blood Test in Four U.S. Health Care Systems. AB - BACKGROUND: To reduce colorectal cancer mortality, positive fecal blood tests must be followed by colonoscopy. METHODS: We identified 62,384 individuals ages 50 to 89 years with a positive fecal blood test between January 1, 2011 and December 31, 2012 in four health care systems within the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. We estimated the probability of follow-up colonoscopy and 95% confidence intervals (CI) using the Kaplan-Meier method. Overall differences in cumulative incidence of follow-up across health care systems were assessed with the log-rank test. HRs and 95% CIs were estimated from multivariate Cox proportional hazards models. RESULTS: Most patients who received a colonoscopy did so within 6 months of their positive fecal blood test, although follow-up rates varied across health care systems (P <0.001). Median days to colonoscopy ranged from 41 (95% CI, 40 41) to 174 (95% CI, 123-343); percent followed-up by 12 months ranged from 58.1% (95% CI, 51.6%-63.7%) to 83.8% (95% CI, 83.4%-84.3%) and differences across health care systems were also observed at 1, 2, 3, and 6 months. Increasing age and comorbidity score were associated with lower follow-up rates. CONCLUSION: Individual characteristics and health care system were associated with colonoscopy after positive fecal blood tests. Patterns were consistent across health care systems, but proportions of patients receiving follow-up varied. These findings suggest that there is room to improve follow-up of positive colorectal cancer screening tests. IMPACT: Understanding the timing of colonoscopy after positive fecal blood tests and characteristics associated with lack of follow-up may inform future efforts to improve follow-up. PMID- 26843523 TI - Artificial White Light vs Daylight Photodynamic Therapy for Actinic Keratoses: A Randomized Clinical Trial. AB - IMPORTANCE: Daylight photodynamic therapy using topical methyl 5-aminolevulinic acid (MAL) for actinic keratoses (AKs) is as effective as conventional photodynamic therapy but has the advantage of being almost pain free. Daylight photodynamic therapy, however, requires dry and warm weather conditions. OBJECTIVE: To establish if topical MAL photodynamic therapy using a white light light-emitting diode (LED) lamp is as effective and well-tolerated as daylight photodynamic therapy for the treatment of AKs. DESIGN, SETTING, AND PARTICIPANTS: Overall, 22 men with significant photodamage and a high number of AKs were enrolled in this prospective, randomized, single-blind study, employing a split scalp design, comparing the effectiveness and adverse effects of daylight photodynamic therapy and artificial white light (AWL) LED photodynamic therapy for the treatment of AKs on the forehead and scalp. Organ transplant recipients were excluded. Patients were treated and evaluated at an academic tertiary referral dermatology center. Treatment lasted from April 2014 to July 2014 and follow-up visits occurred for 9 months posttreatment. INTERVENTIONS: Two symmetrical treatment fields were defined and AKs counted, mapped, and photographed at baseline, 1, 3, 6, and 9 months. Patients had half of their scalp treated with daylight photodynamic therapy and the other half treated with AWL photodynamic therapy 1 week apart and randomly allocated. MAL was applied, and treatment commenced 30 minutes later and lasted 2 hours. Irradiance, illuminance, and light spectra measurements were performed. The integrated dose in J/cm2 was measured. The effective light dose, weighted to the absorption spectrum for protoporphyrin IX, was calculated. MAIN OUTCOMES AND MEASURES: The primary end point was the reduction in total AK count per treatment field. Secondary end points included adverse effects and patient satisfaction. RESULTS: We enrolled 22 men with a median age of 72 years (range, 47-85 years) at baseline, the total (median of AKs per field) were 469 (20.5) for the DPDT group and 496 (20.5) for the AWLPDT group (P = .34). The median number and percentage of reduction in AKs per field were 12 and 62.3% for DPDT and 14 and 67.7% for AWLPDT at 1 month (P = .21 and P = .13, respectively). There was no significant difference in the reduction percentage of AKs for either treatment at 1, 3, and 6 months. At 9 months, the median number and percentage of reduction in AKs per field was 9.0 and 48.4% for DPDT and 12.0 and 64.4% for AWLPDT (P = .13 and P = .05, respectively). Pain was reported by 14 patients with DPDT and 16 patients with AWLPDT (median maximum score [out of 100], 4 vs 6; P = .51). Moderate erythema was reported by 9 patients after DPDT and 14 patients after AWLPDT. On a scale of 0 (intolerable) to 10 (very tolerable) patients rated DPDT as 9.5 and AWLPDT as 9 (P = .37). CONCLUSIONS AND RELEVANCE: Photodynamic therapy using an AWL source was as effective and well-tolerated as daylight photodynamic therapy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02520700. PMID- 26843524 TI - Mapping immune cell infiltration using restricted diffusion MRI. AB - PURPOSE: Diffusion MRI provides a noninvasive way to assess tissue microstructure. Based on diffusion MRI, we propose a model-free method called restricted diffusion imaging (RDI) to quantify restricted diffusion and correlate it with cellularity. THEORY AND METHODS: An analytical relation between q-space signals and the density of restricted spins was derived to quantify restricted diffusion. A phantom study was conducted to investigate the performance of RDI, and RDI was applied to an animal study to assess immune cell infiltration in myocardial tissues with ischemia-reperfusion injury. RESULTS: Our phantom study showed a correlation coefficient of 0.998 between cell density and the restricted diffusion quantified by RDI. The animal study also showed that the high-value regions in RDI matched well with the macrophage infiltration areas in the H&E stained slides. In comparison with diffusion tensor imaging (DTI), RDI exhibited its outperformance to detect macrophage infiltration and delineate inflammatory myocardium. CONCLUSION: RDI can be used to reveal cell density and detect immune cell infiltration. RDI exhibits better specificity than the diffusivity measurement derived from DTI. Magn Reson Med 77:603-612, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26843525 TI - Chromatographic separation of simulants of nerve and blister agents by combining one- and two-channel columns with different stationary phases. AB - A two-channel gas chromatography column and a single-channel column were made by deep reactive-ion etching technology. The two short columns were coated with different stationary phases, and then linked without a modulator. This is to aim at increasing the sample capacity and achieving a higher separation efficiency in complex environments. The results show that the capacity of the connected column is approximately 4 and 1.5 times larger than that of the single- and two-channel columns, respectively. The linked column was utilized to separate a six-component mixture, composed of three simulants of nerve and blister agents and three interfering vapors. The results demonstrate that the combined column has a remarkably higher separation efficiency than the individual columns, and an acceptable resolution is achieved although the total length of the linked column is only 1.5 m. PMID- 26843526 TI - The yjdF riboswitch candidate regulates gene expression by binding diverse azaaromatic compounds. AB - The yjdF motif RNA is an orphan riboswitch candidate that almost exclusively associates with the yjdF protein-coding gene in many bacteria. The function of the YjdF protein is unknown, which has made speculation regarding the natural ligand for this putative riboswitch unusually challenging. By using a structure probing assay for ligand binding, we found that a surprisingly broad diversity of nitrogen-containing aromatic heterocycles, or "azaaromatics," trigger near identical changes in the structures adopted by representative yjdF motif RNAs. Regions of the RNA that undergo ligand-induced structural modulation reside primarily in portions of the putative aptamer region that are highly conserved in nucleotide sequence, as is typical for riboswitches. Some azaaromatic molecules are bound by the RNA with nanomolar dissociation constants, and a subset of these ligands activate riboswitch-mediated gene expression in cells. Furthermore, genetic elements most commonly adjacent to the yjdF motif RNA or to the yjdF protein-coding region are homologous to protein regulators implicated in mitigating the toxic effects of diverse phenolic acids or polycyclic compounds. Although the precise type of natural ligand sensed by yjdF motif RNAs remains unknown, our findings suggest that this riboswitch class might serve as part of a genetic response system to toxic or signaling compounds with chemical structures similar to azaaromatics. PMID- 26843527 TI - The Rtr1p CTD phosphatase autoregulates its mRNA through a degradation pathway involving the REX exonucleases. AB - Rtr1p is a phosphatase that impacts gene expression by modulating the phosphorylation status of the C-terminal domain of the large subunit of RNA polymerase II. Here, we show that Rtr1p is a component of a novel mRNA degradation pathway that promotes its autoregulation through turnover of its own mRNA. We show that the 3'UTR of the RTR1 mRNA contains a cis element that destabilizes this mRNA. RTR1 mRNA turnover is achieved through binding of Rtr1p to the RTR1 mRNP in a manner that is dependent on this cis element. Genetic evidence shows that Rtr1p-mediated decay of the RTR1 mRNA involves the 5'-3' DExD/H-box RNA helicase Dhh1p and the 3'-5' exonucleases Rex2p and Rex3p. Rtr1p and Rex3p are found associated with Dhh1p, suggesting a model for recruiting the REX exonucleases to the RTR1 mRNA for degradation. Rtr1p-mediated decay potentially impacts additional transcripts, including the unspliced BMH2 pre mRNA. We propose that Rtr1p may imprint its RNA targets cotranscriptionally and determine their downstream degradation mechanism by directing these transcripts to a novel turnover pathway that involves Rtr1p, Dhh1p, and the REX family of exonucleases. PMID- 26843528 TI - ATR-101 disrupts mitochondrial functions in adrenocortical carcinoma cells and in vivo. AB - Adrenocortical carcinoma (ACC) generally has poor prognosis. Existing treatments provide limited benefit for most patients with locally advanced or metastatic tumors. We investigated the mechanisms for the cytotoxicity, xenograft suppression, and adrenalytic activity of ATR-101 (PD132301-02), a prospective agent for ACC treatment. Oral administration of ATR-101 inhibited the establishment and impeded the growth of ACC-derived H295R cell xenografts in mice. ATR-101 induced H295R cell apoptosis in culture and in xenografts. ATR-101 caused mitochondrial hyperpolarization, reactive oxygen release, and ATP depletion within hours after exposure, followed by cytochrome c release, caspase 3/7 activation, and membrane permeabilization. The increase in mitochondrial membrane potential occurred concurrently with the decrease in cellular ATP levels. When combined with ATR-101, lipophilic free radical scavengers suppressed the reactive oxygen release, and glycolytic precursors prevented the ATP depletion, abrogating ATR-101 cytotoxicity. ATR-101 directly inhibited F1F0 ATPase activity and suppressed ATP synthesis in mitochondrial fractions. ATR-101 administration to guinea pigs caused oxidized lipofuscin accumulation in the zona fasciculate layer of the adrenal cortex, implicating reactive oxygen release in the adrenalytic effect of ATR-101. These results support the development of ATR 101 and other adrenalytic compounds for the treatment of ACC. PMID- 26843529 TI - Naturally Produced Defensive Alkenal Compounds Activate TRPA1. AB - (E)-2-alkenals are aldehydes containing an unsaturated bond between the alpha and beta carbons. 2-alkenals are produced by many organisms for defense against predators and secretions containing (E)-2-alkenals cause predators to stop attacking and allow the prey to escape. Chemical ecologists have described many alkenal compounds with 3-20 carbons common, having varied positions of double bonds and substitutions. How do these defensive alkenals act to deter predators? We have tested the effects of (E)-2-alkenals with 6-12 carbons on transient receptor potential channels (TRP) commonly found in sensory neurons. We find that (E)-2-alkenals activate transient receptor potential ankyrin subtype 1 (TRPA1) at low concentrations-EC50s 10-100 uM (in 0 added Ca(2+) external solutions). Other TRP channels were either weakly activated (TRPV1, TRPV3) or insensitive (TRPV2, TRPV4, TRPM8). (E)-2-alkenals may activate TRPA1 by modifying cysteine side chains. However, target cysteines include others beyond the 3 in the amino terminus implicated in activation, as a channel with cysteines at 621, 641, 665 mutated to serine responded robustly. Related chemicals, including the aldehydes hexanal and decanal, and (E)-2-hexen-1-ol also activated TRPA1, but with weaker potency. Rat trigeminal nerve recordings and behavioral experiments showed (E)-2 hexenal was aversive. Our results suggest that TRPA1 is likely a major target of these commonly used defensive chemicals. PMID- 26843530 TI - Gasping for answers. Focus on "Calpain activation by ROS mediates human ether-a go-go-related gene protein degradation by intermittent hypoxia". PMID- 26843531 TI - Nicotinic modulation of Ca2+ oscillations in rat cortical neurons in vitro. AB - The roles of nicotine on Ca(2+) oscillations [intracellular Ca(2+) ([Ca(2+)]i) oscillation] in rat primary cultured cortical neurons were studied. The spontaneous [Ca(2+)]i oscillations (SCO) were recorded in a portion of the neurons (65%) cultured for 7-10 days in vitro. Application of nicotine enhanced [Ca(2+)]i oscillation frequency and amplitude, which were reduced by the selective alpha4beta2-nicotinic acetylcholine receptors (nAChRs) antagonist dihydro-beta-erythroidine (DHbetaE) hydrobromide, and the selective alpha7-nAChRs antagonist methyllycaconitine citrate (MLA, 20 nM). DHbetaE reduced SCO frequency and prevented the nicotinic increase in the frequency. DHbetaE somewhat enhanced SCO amplitude and prevented nicotinic increase in the amplitude. MLA (20 nM) itself reduced SCO frequency without affecting the amplitude but blocked nicotinic increase in [Ca(2+)]i oscillation frequency and amplitude. Furthermore, coadministration of both alpha4beta2- and alpha7-nAChRs antagonists completely prevented nicotinic increment in [Ca(2+)]i oscillation frequency and amplitude. Thus, our results indicate that both alpha4beta2- and alpha7-nAChRs mediated nicotine-induced [Ca(2+)]i oscillations, and two nAChR subtypes differentially regulated SCO. PMID- 26843532 TI - Non-invasive imaging to identify susceptibility for ventricular arrhythmias in ischaemic left ventricular dysfunction. AB - OBJECTIVE: Non-invasive imaging of myocardial perfusion, sympathetic denervation and scar size contribute to enhanced risk prediction of ventricular arrhythmias (VA). Some of these imaging parameters, however, may be intertwined as they are based on similar pathophysiology. The aim of this study was to assess the predictive role of myocardial perfusion, sympathetic denervation and scar size on the inducibility of VA in patients with ischaemic cardiomyopathy in a head-to head fashion. METHODS: 52 patients with ischaemic heart disease and left ventricular ejection fraction (LVEF) <=35%, referred for primary prevention implantable cardioverter-defibrillator (ICD) implantation, were included. Late gadolinium-enhanced cardiovascular MRI was performed to assess LV volumes, function and scar size. Using [(15)O]H2O and [(11)C]hydroxyephedrine positron emission tomography, both resting and hyperaemic myocardial blood flow (MBF), and sympathetic innervation were assessed. After ICD implantation, an electrophysiological study (EPS) was performed and was considered positive in case of sustained VA. RESULTS: Patients with a positive EPS (n=25) showed more severely impaired global hyperaemic MBF (p=0.003), larger sympathetic denervation size (p=0.048) and tended to have larger scar size (p=0.07) and perfusion defect size (p=0.06) compared with EPS-negative patients (n=27). No differences were observed in LV volumes, LVEF and innervation-perfusion mismatch size. Multivariable analysis revealed that impaired hyperaemic MBF was the single best independent predictor for VA inducibility (OR 0.78, 95% CI 0.65 to 0.94, p=0.007). A combination of risk markers did not yield incremental predictive value over hyperaemic MBF alone. CONCLUSIONS: Of all previously validated approaches to evaluate the arrhythmic substrate, global impaired hyperaemic MBF was the only independent predictor of VA inducibility. Moreover, a combined approach of different imaging variables did not have incremental value. PMID- 26843533 TI - The incidence of chromosome abnormalities in neonates with structural heart disease. AB - OBJECTIVES: This study was conducted to determine the prevalence of chromosomal anomalies in newborns with structural heart disease admitted to the cardiac intensive care unit (CICU) at Nicklaus Children's Hospital (NCH). METHODS: A retrospective review identified newborns age 30 days or less admitted to NCH CICU between 2004 and 2010. Patients with structural heart disease who required admission to our CICU and received karyotype or karyotype and fluorescent in situ hybridization (FISH) testing were included in the study. All patients were examined for the presence of dysmorphic features. RESULTS: Four hundred and eighty-two patients met the criteria for the study; 405 (84%) received both karyotype and FISH. Chromosome abnormalities were present in 86 (17.8%) patients. Syndromes accounted for 20 (5.1%) of those with normal chromosomes. Dysmorphic features were seen in 79.1% of patients with abnormal chromosomes and 25.5% of those with normal chromosomes. All patients with syndromes were dysmorphic. Race and gender did not significantly affect the incidence of genetic abnormalities. CONCLUSIONS: Chromosome abnormalities, including syndromes, are prevalent in newborns with congenital heart disease. Further research is needed to evaluate the utility of cytogenetic screening in all children with congenital heart disease. PMID- 26843534 TI - Internal Medicine Residents' Beliefs, Attitudes, and Experiences Relating to Palliative Care: A Qualitative Study. AB - BACKGROUND: Internal medicine residents are frequently called upon to provide palliative care to hospitalized patients, but report feeling unprepared to do so effectively. Curricular development to enhance residents' palliative care skills and competencies requires an understanding of current beliefs, attitudes and learning priorities. METHODS: We conducted a qualitative study consisting of semi structured interviews with ten internal medicine residents to explore their understanding of and experiences with palliative care. RESULTS: All of the residents interviewed had a sound theoretical understanding of palliative care, but faced many challenges in being able to provide care in practice. The challenges described by residents were system-related, patient-related and provider-related. They identified several priority areas for further learning, and discussed ways in which their current education in palliative care could be enhanced. CONCLUSIONS: Our findings provide important insights to guide curricular development for internal medicine trainees. The top five learning priorities in palliative care that residents identified in our study were: 1) knowing how and when to initiate a palliative approach, 2) improving communication skills, 3) improving symptom management skills, 4) identifying available resources, and 5) understanding the importance of palliative care. Residents felt that their education in palliative care could be improved by having a mandatory rotation in palliative care, more frequent didactic teaching sessions, more case-based teaching from palliative care providers, opportunities to be directly observed, and increased support from palliative care providers after-hours. PMID- 26843535 TI - Evaluation of Pain, Dyspnea, and Goals of Care Among Adults With Cystic Fibrosis: A Comprehensive Palliative Care Survey. AB - BACKGROUND: Palliative care is increasingly important in the care of adults with cystic fibrosis (CF). Symptoms such as pain and dyspnea are prevalent, yet severity may be underestimated. Little information is available to describe patient preferences for end-of-life care (EOLC). The objective of this study was to describe patient perceptions about pain, dyspnea, and advance care planning. METHODS: We developed a survey to assess pain, dyspnea, and EOLC in adults with CF. Questions were compiled and adapted from existing tools. The survey was administered to all patients in a single adult CF care center. Descriptive data were compiled as counts (proportions) and median (25th and 75th percentile). Mann Whitney U test was used to determine differences between individuals who experienced pain and dyspnea. A P value of .05 was utilized to determine significance. RESULTS: Thirty-seven of 43 surveys were returned. Twenty-four percent reported chronic pain. Patients who reported pain with airway clearance had lower lung function (predicted forced expiratory volume in 1 [FEV1] 42% vs 65%, P < .05) and body mass index (19.6 vs 22.3, P < .05) than patients without pain. Those reporting dyspnea at rest had lower median FEV1 (28% vs 61%, P < .05). Patients with lower lung function are more likely to have considered end-of life decisions (73% vs 31%, P < .05). CONCLUSION: Pain and dyspnea are common among adults with CF. Few had an advance directive in place, but most are open to discussing EOLC issues. Results of this single-center study may not represent the entire population, thus a multicenter investigation should be pursued. PMID- 26843536 TI - Effects of aerobic and muscle strengthening exercise in adults with rheumatoid arthritis: a narrative review summarising a chapter in Physical activity in the prevention and treatment of disease (FYSS 2016). AB - BACKGROUND: Besides pharmacological treatment, regular exercise is one of the cornerstones of care in rheumatoid arthritis (RA). In many of the earlier studies of exercise in RA, the intensity of the exercise did not reach the current recommendations or is not described in satisfactory detail. This narrative review is based on randomised controlled trials with a detailed description of the exercise type, frequency, duration and intensity. RESULTS: There is moderate quality evidence that short-term land-based aerobic exercise of moderate to high intensity augments oxygen uptake but does not improve muscle strength. Short-term water-based aerobic exercise of moderate to high intensity augments oxygen uptake; short term land-based aerobic and muscle strengthening exercise of moderate to high intensity augments oxygen uptake and muscle strength. Long-term land-based aerobic and muscle strengthening exercise of moderate to high intensity reduces activity limitations and improves both oxygen uptake and muscle strength. CONCLUSIONS: Clinicians should recommend that patients with RA participate in various types of exercise. PMID- 26843537 TI - Time to bin the term 'overuse' injury: is 'training load error' a more accurate term? PMID- 26843538 TI - A combination of initial and follow-up physiotherapist examination predicts physician-determined time to return to play after hamstring injury, with no added value of MRI. AB - BACKGROUND: Previous studies investigating prediction of return to play after acute hamstring injury were limited by examining a single postinjury clinical and MRI evaluation. We evaluated the added value of including follow-up clinical evaluation when predicting return to play. METHODS: A range of clinical and MRI parameters were prospectively investigated for an association with the time to return to play in 90 athletes with MRI positive hamstring injuries undergoing a criteria-based rehabilitation programme. Clinical evaluation was performed within 5 days of injury and 7 days after this initial assessment (follow-up clinical evaluation). The association between possible prognostic parameters and the time to return to play was assessed with a multiple linear regression model. RESULTS: Data of 90 athletes were available for analysis. At the first physiotherapy appointment, a combination of three demographic and six clinical variables explained 50% of the variance (+/-19 days) in the time to return to play. At follow-up assessment (7 days), a combination of 10 clinical and demographic variables explained 97.0% of the variance (+/-5 days) in time to return to play. In order of importance, the variables were: change in strength during the first week for the 'mid-range' test, peak isokinetic knee flexion torque of the uninjured leg, maximum pain at the time of injury, number of days to walk pain free, playing the sport of football, strength performing the 'inner range' hamstring test at day 1, presence of pain on a single leg bridge at day 7 or its absence during a single leg bridge, delay in starting treatment and percentage of strength in the 'outer range' test compared to the healthy leg. No MRI variables were retained in any of these analyses. MRI variables alone explained 8.6% of the variance-which is unhelpful to players and coaches. SUMMARY: The combination of initial and 7-day follow-up clinical evaluation is clinically helpful in predicting time to return to play (+/-5 days) following acute hamstring injury. MRI offered no useful clinical information regarding return to play duration in this cohort. TRIAL REGISTRATION NUMBER: NCT01812564. PMID- 26843539 TI - Trends in 'poor responder' research: lessons learned from RCTs in assisted conception. AB - BACKGROUND: A substantial minority of women undergoing IVF will under-respond to controlled ovarian hyperstimulation. These women-so-called 'poor responders' suffer persistently reduced success rates after IVF. Currently, no single intervention is unanimously accepted as beneficial in overcoming poor ovarian response (POR). This has been supported by the available research on POR, which consists mainly of randomized controlled trials (RCTs ) with an inherent high risk of bias. The aim of this review was to critically appraise the available experimental trials on POR and provide guidance towards more useful-less wasteful future research. METHODS: A comprehensive review was undertaken of RCTs on 'poor responders' published in the last 15 years. Data on various methodological traits as well as important clinical characteristics were extracted from the included studies and summarized, with a view to identifying deficiencies from which lessons can be learned. Based on this analysis, recommendations were provided for further research in this field of assisted conception. RESULTS: We selected and analysed 75 RCTs. A valid, 'low-risk' randomization method was reported in three out of four RCTs. An improving trend in reporting concealment of patient allocation was also evident over the 15-year period. In contrast, <1 in 10 RCTs 'blinded' patients and <1 in 5 RCTs 'blinded' staff to the proposed intervention. Only 1 in 10 RCTs 'blinded' ultrasound practitioners to patient allocation, when assessing the outcome of early pregnancy. The majority of trials reported an intention-to-treat analysis for at least one of their outcomes, with an improving trend in the recent years. Substantial variation was noted in the definitions used for 'poor responders', the most popular being 'low ovarian response at previous stimulation'. The preferred cut-off value for defining previous low response has been 'less or equal to three retrieved oocytes'. The most popular tests used for diagnosing diminished ovarian reserve have been antral follicle count and FSH. Although the Bologna criteria for POR were only recently introduced, they are expected to become a popular definition in future 'poor responder' trials. Numerous interventions have been studied on 'poor responders'. Most of these have been applied before/during controlled ovarian hyperstimulation. The antagonist protocol, the microdose flare protocol and the long down-regulation protocol have been among the most popular interventions. The analysis of outcomes revealed a clear improving trend in reporting live birth. In contrast, only 10% of RCTs reported significant improvement in reproductive outcomes among tested interventions. Twelve 'significant' interventions were reported, each supported by a single 'positive' RCT. Finally, trials of higher methodological quality were more likely to have been published in a high-impact journal. CONCLUSIONS: Overall, the majority of published trials on POR suffer from methodological flaws and are, thus, regarded as being high-risk for bias. The same trials have used a variety of definitions for their poor responders and a variety of interventions for their head-to-head comparisons. Not surprisingly, discrepancies are also evident in the findings of trials comparing similar interventions. Based on the identified deficiencies, this novel type of 'methodology and clinical' review has introduced custom recommendations on how to improve future experimental research in the 'poor responder' population. PMID- 26843540 TI - Left Atrial Structure and Function Across the Spectrum of Cardiovascular Risk in the Elderly: The Atherosclerosis Risk in Communities Study. AB - BACKGROUND: Although left atrial (LA) enlargement is a recognized risk factor for adverse cardiovascular outcomes, emerging evidence supports the importance of LA function. We examined LA emptying fraction (LAEF) across the spectrum of cardiovascular disease burden in a large cohort of elderly adults living in the community. METHODS AND RESULTS: We studied 1142 participants in the Atherosclerosis Risk in Communities (ARIC) study who were in sinus rhythm, free of valvular disease, and had acceptable quality 3-dimensional echocardiograms (mean age, 76+/-5 years; 59% women). We determined the cross-sectional correlates of LAEF and compared LAEF among elderly adults without cardiovascular disease or cardiovascular risk factors (n=201), those with hypertension (n=734), and those with overt heart failure (HF; n=207). In multivariable analysis, lower LAEF was associated with higher LA volumes and worse left ventricular systolic and diastolic functions. Elderly participants free of cardiovascular disease or risk factors had smaller LA volumes than those with hypertension (LA volume max/ body surface area 30.2+/-6.6 versus 33.0+/-9.0 mL/m(2); P=0.001), but similar LAEF (55.2+/-10.3% versus 53.8+/-11.5%, respectively; P=0.357). Participants with HF had higher LA volume (39.8+/-13.3 mL/m(2)) and worse LAEF (47.6+/-14.6%) than participants with hypertension or participants free of cardiovascular disease or risk factors (all P<0.001). CONCLUSIONS: In a community-based cohort, LA function was impaired in participants with prevalent HF, but there were no significant differences in LA function between participants with hypertension and those with free of cardiovascular disease or risk factors, despite greater LA size in the former. PMID- 26843541 TI - Left Atrial Morphology and Function: The Other Side of Cardiovascular Risk. PMID- 26843543 TI - Characterization and Surgical Management of Achilles Tendon Sleeve Avulsions. AB - BACKGROUND: An Achilles sleeve avulsion occurs when the tendon ruptures distally from its calcaneal insertion as a continuous "sleeve." This relatively rare injury pattern may not be appreciated until the time of surgery and can be challenging to treat because, unlike a midsubstance rupture, insufficient tendon remains on the calcaneus to allow for end-to-end repair, and unlike a tuberosity avulsion fracture, any bony element avulsed with the tendon is inadequate for internal fixation. This study aimed to highlight the characteristics of Achilles sleeve avulsions and present the outcomes of operative repair using suture anchor fixation. METHODS: A retrospective analysis was conducted on 11 consecutive Achilles tendon sleeve avulsions (10 males, 1 female; mean age 44 years) that underwent operative repair between 2008 and 2014. Patient demographics, injury presentation, and operative details were reviewed. Postoperative outcomes were collected at a mean follow-up of 38.4 (range, 12-83.5) months, including the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot score, visual analog scale (VAS) for pain, plantarflexion strength, patient satisfaction, and complications. RESULTS: Eight patients (72.7%) had preexisting symptoms of insertional Achilles disease. Ten of 11 (90.9%) injuries were sustained during recreational athletic activity. An Achilles sleeve avulsion was recognized preoperatively in 7 of 11 (64%) cases, where lateral ankle radiographs demonstrated a small radiodensity several centimeters proximal to the calcaneal insertion. Intraoperatively, 90.9% of sleeve avulsions had a concomitant Haglund deformity and macroscopic evidence of insertional tendinopathy. All patients healed after suture anchor repair. The average AOFAS score was 92.8 and VAS score was 0.9. Ten patients (90.9%) were completely satisfied. One complication occurred, consisting of delayed wound healing. CONCLUSIONS: Achilles tendon sleeve avulsions predominantly occurred in middle-aged men with preexisting insertional disease, while engaged in athletic activity. Suture anchor fixation, combined with addressing concomitant insertional pathology, was a reliable and safe technique for the operative management of Achilles tendon sleeve avulsions. The majority of patients returned to their preinjury levels of work and recreational activity. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 26843542 TI - Copeptin Levels Do Not Correlate With Cross-Clamping Time in Patients Undergoing Carotid Endarterectomy Under General Anesthesia. AB - Copeptin is a sensitive and more stable surrogate marker for arginine vasopressin. In this study, we evaluated copeptin levels in carotid endarterectomy (CEA) patients, perioperatively, to determine whether copeptin levels can be related to carotid artery cross clamping (CC) time and to postoperative neurological outcomes. Copeptin, interleukin 6, C-reactive protein, cortisol, and brain natriuretic peptide were measured preoperatively (T1) and 3 hours postoperatively (T3) as well as intraoperatively (T2). We recruited 77 patients. Values of copeptin rose gradually over the observed times: T1 = 7.9 (6.4-9.6), T2 = 12.6 (9.3-16.8), and T3 = 72.3 (49.1-111.2) pmol/L. There was a significant difference for repeated measurement ( P = .000, P = .000, and P = .000). Duration of carotid artery CC during CEA does not affect postoperative copeptin level (CC <= 13 minutes: 106.8 +/- 93.6 pmol/L, CC > 13 minutes: 96.7 +/ 89.1 pmol/L; P = .634). Preoperative copeptin level was significantly higher in patients with ulcerated plaque morphology. Activation of the stress axis in patients undergoing CEA results in copeptin elevation. Duration of CC during CEA does not affect postoperative copeptin levels. PMID- 26843544 TI - Lesser Toe PIP Joint Resection Versus PIP Joint Fusion: A Randomized Clinical Trial. AB - BACKGROUND: It is unclear whether proximal interphalangeal joint (PIPJ) resection or fusion leads to superior clinical outcome in patients undergoing hammertoe surgery. The purpose of this study was to prospectively evaluate a series of patients undergoing this surgery. METHODS: Patients with one or more toes with rigid PIP flexion deformity were prospectively enrolled. These patients were randomly assigned to undergo either PIPJ resection or PIPJ fusion. In addition to the PIPJ procedure, a metatarsophalangeal joint (MTPJ) release was performed if deemed necessary. Follow-up was up to 1 year postoperatively. Twenty-six patients (39 toes) were included in the PIPJ resection group and 29 (50 toes) in the PIPJ fusion group. RESULTS: Thirty-four underwent an MTPJ release. No significant difference in foot outcome scores (American Orthopaedic Foot & Ankle Society scale, the Foot Function Index, and visual analog scale pain) could be detected after 1-year follow-up. A statistically significant difference was found regarding the toe alignment in the sagittal plane in favor of PIPJ fusion. CONCLUSIONS: Our randomized controlled study did not show any clinical outcome difference between PIPJ fusion and PIPJ resection. Both procedures resulted in good to excellent outcome in pain and activity scores. LEVEL OF EVIDENCE: Level II, lesser quality RCT or prospective comparative study. PMID- 26843545 TI - MRI Evaluation of Achilles Tendon Rotation and Sural Nerve Anatomy: Implications for Percutaneous and Limited-Open Achilles Tendon Repair. AB - BACKGROUND: Limited-open and percutaneous Achilles tendon (AT) repair techniques have limited visibility, which may result in sural nerve violation and poor tendon targeting. The goal of this study was to assess the in vivo rotation of the AT and its distance to the sural nerve in ruptured and nonruptured ATs to develop guidelines to aid in limited-open and percutaneous repair techniques. METHODS: A retrospective review was conducted to identify magnetic resonance imaging (MRI) studies of patients with ruptured and healthy (nonruptured) ATs. AT rotation and distance to the sural nerve in the anterior-posterior (A-P) and medial-lateral (M-L) planes were measured at the level of and proximal to the ankle. RESULTS: The AT was externally rotated in both ruptured and nonruptured cohorts. Ruptured ATs showed greater external rotation than nonruptured ATs at the ankle (15.8 +/- 16.2 degrees vs 5.9 +/- 9.0 degrees, P = .008) but not at 10 cm proximal to the tendon's insertion (10.9 +/- 10.9 degrees vs 6.1 +/- 8.4 degrees, P = .139). Proximal AT rotation was negatively correlated with rupture height (r = -0.477, P = .029). At 4 cm proximal to the AT insertion, the sural nerve was closer anteriorly to and farther laterally from the AT in ruptures than in nonruptures (P < .001). At 10 cm proximal to the AT insertion, the sural nerve was farther posteriorly and laterally from the AT in ruptures than in nonruptures (P = .027 and P < .001, respectively). CONCLUSION: We found that the AT was more externally rotated in ruptured than in nonruptured tendons at the ankle and that its distance to the sural nerve differed between the 2 cohorts in the A-P and M-L planes, likely due to increased AT rotation and swelling with ruptures. To minimize sural nerve injury and improve tendon targeting, we suggest an external rotation of 11 degrees at the proximal end of the rupture and 16 degrees at the distal end when using percutaneous and limited-open AT repair devices to try to minimize sural nerve violation and increase tendon capture, which can decrease rates of complication and rerupture. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 26843546 TI - Rate of Malunion Following Bi-plane Chevron Medial Malleolar Osteotomy. AB - BACKGROUND: Access to the medial half of the talus can be challenging even with an osteotomy. Although several techniques are presented in the literature, critical evaluation of fixation, union, and alignment is lacking. The chevron medial malleolar osteotomy provides advantages of perpendicular instrumentation access and wide exposure to the medial talus. Postoperative displacement resulting in malunion, and possibly provoking ankle osteoarthritis, is a known complication. The present study describes our experience with the osteotomy. METHODS: A consecutive series cohort of 50 bi-plane chevron osteotomies performed from 2004 to 2013 were evaluated. Forty-six were secured using 2 lag screws, and 4 were secured using 2 lag screws and a medial buttress plate. Radiographic studies performed at 2, 6, and 12 weeks and at final follow-up were analyzed for postoperative displacement, malunion, non-union, and hardware-related complications. RESULTS: At initial postoperative follow-up, 47 of 50 had adequate radiographs for review, and 18 of 47 (38.3%) showed some displacement when compared to the initial osteotomy fixation position. By final follow-up, 15 of 50 (30.0%) had measurable incongruence. Hardware removal was performed in 13 (26.0%) cases at an average of 2.4 years postoperation. CONCLUSION: Bi-plane medial malleolar chevron osteotomy fixed with 2 lag screws showed a 30.0% malunion rate with an average of 2 mm of incongruence on final follow-up radiographs, which is higher than what has been reported in the literature. In our practice, we now use a buttress plate and more recently have eliminated postoperative osteotomy displacement. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 26843547 TI - Computed Tomographic Evaluation of Joint Geometry in Patients With End-Stage Ankle Osteoarthritis. AB - BACKGROUND: Deformation of the talus and the distal tibia can be frequently observed during ankle joint osteoarthritis (OA). The aim of this study was to objectify these morphologic changes. We hypothesized that a flattening of the talus and a broadening of the distal tibia surface occurs in end-stage OA of the ankle joint. METHODS: Twenty-seven computed tomography (CT) ankle joint examinations of unilateral ankle OA were matched by sex and age with 27 CT examinations of healthy ankle joints. Three-dimensional reformatting and measurements were performed with geometry analysis software. The following parameters were assessed: sagittal radius of the talus, talus height, and mediolateral and anteroposterior width of the distal tibial joint surface. RESULTS: Medial, midsagittal, and lateral sagittal arc radii of osteoarthritic tali were significantly larger compared to tali of controls. There was a statistically significant difference in the height of the osteoarthritic talar dome in the medial and in the lateral frontal segment and in the medial central segment compared to tali of controls. The anteroposterior width and the sagittal curvature of the distal tibia was significantly larger in OA ankles than in the control group. The mediolateral measurements were comparable across both groups. CONCLUSION: Flattening of the talus appears to be more pronounced in the frontal aspect of the talus. The distal tibia broadens anteroposteriorly. These findings may contribute to better understanding of ankle OA development. LEVEL OF EVIDENCE: Level III, retrospective comparative cohort study. PMID- 26843548 TI - Nurse staffing and the work environment linked to readmissions among older adults following elective total hip and knee replacement. AB - OBJECTIVE: To examine the effect of nurse staffing and the work environment on 10 and 30-day unplanned readmissions for US Medicare patients following elective total hip and knee replacement. DESIGN: A cross-sectional analysis of secondary data. SETTING: Acute care hospitals in California, Florida, New Jersey and Pennsylvania, during 2006. PARTICIPANTS: Medicare patients (n = 112 017) admitted to an acute care hospital for an elective total hip or knee replacement. MAIN OUTCOME MEASURES: The adjusted odds ratio (OR) of experiencing an unplanned readmission within 10 and 30 days of discharge following an elective total hip or knee replacement. RESULTS: Our sample included 112 017 Medicare patients in 495 hospitals. Nearly 6% of the patients were readmitted within 30 days; more than half of whom were rehospitalized within 10 days. Adjusted for patient and hospital characteristics, patients had 8% higher odds of 30-day readmission and 12% higher odds of 10-day readmission, for each additional patient per nurse. Patients cared for in the best work environments had 12% lower odds of 30-day readmission. CONCLUSIONS: Readmission outcomes following major joint replacement are associated with hospital nursing care. Attention to nurse work conditions may be central to improving readmissions in this postoperative Medicare population. PMID- 26843549 TI - Re: A systematic review of patients' experiences of adverse events in health care. PMID- 26843550 TI - ILLNESS IS WORK: Revisiting the concept of illness careers and recognizing the identity work of patients with ME/CFS. AB - The concept of careers has an extensive history in the sociology of health and illness. Among other things, the notion of a career has been used to describe the changing identities of patients diagnosed with mental illness, to identify distinct stages in the progression of various illnesses, and to recognize the cooperative efforts of hospitalized patients. However, the career concept may be reanalyzed as part of an analytical metaphor that makes salient both the agency of people with illnesses and the social structures in which they are enmeshed. This metaphor, ILLNESS IS WORK, can valorize and aid understanding of the identity work and actions of patients with chronic illnesses, particularly illnesses with a low degree of social recognition and medical prestige such as myalgic encephalopathy and chronic fatigue syndrome. PMID- 26843551 TI - Considering all the evidence: a reply to Sefc and Koblmuller (2016). PMID- 26843552 TI - The dilemma of trade samples and the importance of museum vouchers--caveats from a study on the extinction of Steller's sea cow: a comment on Crerar et al. (2014). PMID- 26843553 TI - Serendipity in research--investigation into illegal wildlife trade discovers a new population of Steller's sea cows: a reply to Pyenson et al. (2016). PMID- 26843554 TI - Ancient hybrid origin of the eastern wolf not yet off the table: a comment on Rutledge et al. (2015). AB - A recent study of North American canids by Rutledge et al. (Biol. Lett. 11, 20150303 (doi:10.1098/rsbl.2015.0303)) refutes the hypothesized hybrid origin of the eastern wolf (EW) based on genomic evidence against very recent hybridization. However, the analyses do not rule out the possibility of more ancient hybridization. Claims to have resolved the evolutionary origin of the EW are therefore inappropriate. Importantly, though, we plead that uncertainty about the ancient history of the taxon should not affect current conservation policy. PMID- 26843555 TI - Does absolute brain size really predict self-control? Hand-tracking training improves performance on the A-not-B task. AB - Large-scale, comparative cognition studies are set to revolutionize the way we investigate and understand the evolution of intelligence. However, the conclusions reached by such work have a key limitation: the cognitive tests themselves. If factors other than cognition can systematically affect the performance of a subset of animals on these tests, we risk drawing the wrong conclusions about how intelligence evolves. Here, we examined whether this is the case for the A-not-B task, recently used by MacLean and co-workers to study self control among 36 different species. Non-primates performed poorly on this task; possibly because they have difficulty tracking the movements of a human demonstrator, and not because they lack self-control. To test this, we assessed the performance of New Caledonian crows on the A-not-B task before and after two types of training. New Caledonian crows trained to track rewards moved by a human demonstrator were more likely to pass the A-not-B test than birds trained on an unrelated choice task involving inhibitory control. Our findings demonstrate that overlooked task demands can affect performance on a cognitive task, and so bring into question MacLean's conclusion that absolute brain size best predicts self control. PMID- 26843556 TI - UV wavelengths experienced during development affect larval newt visual sensitivity and predation efficiency. AB - We experimentally investigated the influence of developmental plasticity of ultraviolet (UV) visual sensitivity on predation efficiency of the larval smooth newt, Lissotriton vulgaris. We quantified expression of SWS1 opsin gene (UV sensitive protein of photoreceptor cells) in the retinas of individuals who had developed in the presence (UV+) or absence (UV-) of UV light (developmental treatments), and tested their predation efficiency under UV+ and UV- light (testing treatments). We found that both SWS1 opsin expression and predation efficiency were significantly reduced in the UV- developmental group. Larvae in the UV- testing environment displayed consistently lower predation efficiency regardless of their developmental treatment. These results prove for the first time, we believe, functional UV vision and developmental plasticity of UV sensitivity in an amphibian at the larval stage. They also demonstrate that UV wavelengths enhance predation efficiency and suggest that the magnitude of the behavioural response depends on retinal properties induced by the developmental lighting environment. PMID- 26843557 TI - Conjugation is necessary for a bacterial plasmid to survive under protozoan predation. AB - Horizontal gene transfer by conjugative plasmids plays a critical role in the evolution of antibiotic resistance. Interactions between bacteria and other organisms can affect the persistence and spread of conjugative plasmids. Here we show that protozoan predation increased the persistence and spread of the antibiotic resistance plasmid RP4 in populations of the opportunist bacterial pathogen Serratia marcescens. A conjugation-defective mutant plasmid was unable to survive under predation, suggesting that conjugative transfer is required for plasmid persistence under the realistic condition of predation. These results indicate that multi-trophic interactions can affect the maintenance of conjugative plasmids with implications for bacterial evolution and the spread of antibiotic resistance genes. PMID- 26843559 TI - Neurofascin-155 IgG4 in chronic inflammatory demyelinating polyneuropathy. AB - OBJECTIVE: We report the clinical and serologic features of Japanese patients with chronic inflammatory demyelinating polyneuropathy (CIDP) displaying anti neurofascin-155 (NF155) immunoglobulin G4 (IgG4) antibodies. METHODS: In sera from 533 patients with CIDP, anti-NF155 IgG4 antibodies were detected by ELISA. Binding of IgG antibodies to central and peripheral nerves was tested. RESULTS: Anti-NF155 IgG4 antibodies were identified in 38 patients (7%) with CIDP, but not in disease controls or normal participants. These patients were younger at onset as compared to 100 anti-NF155-negative patients with CIDP. Twenty-eight patients (74%) presented with sensory ataxia, 16 (42%) showed tremor, 5 (13%) presented with cerebellar ataxia associated with nystagmus, 3 (8%) had demyelinating lesions in the CNS, and 20 of 25 (80%) had poor response to IV immunoglobulin. The clinical features of the antibody-positive patients were statistically more frequent as compared to negative patients with CIDP (n = 100). Anti-NF155 IgG antibodies targeted similarly central and peripheral paranodes. CONCLUSION: Anti NF155 IgG4 antibodies were associated with a subgroup of patients with CIDP showing a younger age at onset, ataxia, tremor, CNS demyelination, and a poor response to IV immunoglobulin. The autoantibodies may serve as a biomarker to improve patients' diagnosis and guide treatments. PMID- 26843561 TI - Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy. AB - OBJECTIVE: To investigate the histopathologic substrate of microbleeds detected on 7T postmortem MRI in autopsy cases with severe cerebral amyloid angiopathy (CAA) and Alzheimer pathology. METHODS: Five decedents (mean age at death 79.6 +/ 5.7 years) with documented severe CAA and Alzheimer pathology on standard neuropathologic examination were selected from a local database. Formalin-fixed coronal brain slices were scanned at 7T MRI, including high-resolution T2- and T2*-weighted sequences. Representative microbleeds from each case were sampled for histopathologic analysis, including the presence of blood, blood breakdown products, and markers of ischemic tissue injury. RESULTS: On MRI, we identified >300 cortical and 4 subcortical microbleeds. Two out of 15 sampled cortical microbleeds corresponded histologically to erythrocytes (suggestive of recent hemorrhages), 4 to vasculopathies (fibrinoid necrosis in 3 and a cavernoma) without substantial parenchymal tissue injury, and 9 to accumulations of iron positive siderophages without erythrocytes (suggestive of old hemorrhages) combined with mild to moderate degrees of chronic ischemic tissue injury. CONCLUSIONS: This study provides evidence for heterogeneous pathologic substrates and possibly different pathophysiologic mechanisms underlying MRI-observed cortical microbleeds in the context of advanced CAA and Alzheimer disease. PMID- 26843560 TI - Cutaneous adverse events in multiple sclerosis patients treated with daclizumab. AB - OBJECTIVE: To analyze the spectrum and mechanisms of cutaneous adverse events (AEs) in patients with multiple sclerosis treated with daclizumab high-yield process (DAC-HYP). METHODS: A total of 31 participants in an institutional review board-approved open-label phase I study of DAC-HYP (NCT01143441) were prospectively evaluated over 42 months for development of cutaneous AEs. Participants provided written informed consent. Fifteen participants were naive to anti-CD25 therapy (cohort B), while 16 had received daclizumab (Zenapax; Hoffmann-La Roche) IV for 4-9 years (mean 5.8 years) prior to enrollment (cohort A). Immunohistochemistry was performed on pretreatment and posttreatment skin biopsies of normal-appearing skin (cohort B only) and on lesional biopsies in participants presenting with rash (both cohorts). RESULTS: Cutaneous AEs occurred in 77% of patients, the majority presenting with patches of eczema requiring no treatment. Moderate to severe rash developed in 6 participants (19%) and required discontinuation of DAC-HYP in 4 (13%). More severe rashes presented psoriasiform phenotype, but lesional biopsies lacked features of either psoriasis or drug hypersensitivity eruptions. Instead, irrespective of clinical severity, lesional biopsies showed nonspecific features of eczematous dermatitis, but with prominent CD56+ lymphocytic infiltrates. Pretreatment and posttreatment biopsies of normal appearing skin demonstrated no histopathologic changes. CONCLUSIONS: Observed cutaneous AEs are likely related to the immunomodulatory effects DAC-HYP exerts on innate lymphoid cells, including natural killer cells. Vigilance and timely management of skin reactions may prevent treatment discontinuation in participants with severe rash. PMID- 26843563 TI - Close to the node but far enough: What nodal antibodies tell us about CIDP and its therapies. PMID- 26843562 TI - Amyloid pathology and axonal injury after brain trauma. AB - OBJECTIVE: To image beta-amyloid (Abeta) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Abeta are correlated, and compare the spatial distribution of Abeta to Alzheimer disease (AD). METHODS: Patients 11 months to 17 years after moderate-severe TBI underwent (11)C-Pittsburgh compound B ((11)C-PiB)-PET, structural and diffusion MRI, and neuropsychological examination. Healthy aged controls and patients with AD underwent PET and structural MRI. Binding potential (BPND) images of (11)C-PiB, which index Abeta plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy, was estimated and correlated with (11)C-PiB BPND. RESULTS: Twenty-eight participants (9 with TBI, 9 controls, 10 with AD) were assessed. Increased (11)C-PiB BPND was found in TBI vs controls in the posterior cingulate cortex and cerebellum. Binding in the posterior cingulate cortex increased with decreasing fractional anisotropy of associated white matter tracts and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions but increased in the cerebellum. CONCLUSIONS: Increased Abeta burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathologic features of dementia, which may relate to axonal damage produced by the injury. PMID- 26843564 TI - CSTB null mutation associated with microcephaly, early developmental delay, and severe dyskinesia. PMID- 26843565 TI - Comment: Outcomes of migraine therapy with IV dihydroergotamine. PMID- 26843566 TI - Referred facial sensation on the hand after full face transplantation. AB - OBJECTIVE: Using a single patient case study, we aimed to look at the interaction between full face transplantation and subsequent somatosensory representation in the cortex. METHODS: We present a patient with full face transplantation who has recovered primary sensory modalities. The patient also has facial sensations such as touch perception in sensory examinations of the hands and fingers. RESULTS: fMRI findings show interactions between the cortical representations of the face and hand. CONCLUSION: This phenomenon is one of the well-known referred sensations and reveals how face transplantation relates to cortical plasticity. PMID- 26843567 TI - Amyloid plaques in TBI: Incidental finding or precursor for what is to come? PMID- 26843568 TI - Comment: Reorganization alters sensory perception after full face transplantation. PMID- 26843569 TI - Exacerbation of headache during dihydroergotamine for chronic migraine does not alter outcome. AB - OBJECTIVE: To evaluate whether headache exacerbation associated with IV dihydroergotamine (DHE) infusion predicts medium-term headache outcome in patients with chronic migraine. METHODS: This was a retrospective chart review study of the UCSF Headache Center's use of IV DHE for chronic migraine from 2008 to 2012. Medium-term headache outcome was assessed at 6-week follow-up. Univariate and multivariate logistic regression models were used to assess for predictors of outcome. RESULTS: Patients with chronic migraine (n = 274) were treated with a course of IV DHE. Of 214 with 6-week follow-up, 78% had medium term headache benefit. In a univariate logistic regression model, headache exacerbation with DHE was associated with lower odds of a positive medium-term headache outcome (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.20-0.91). However, in the multivariate logistic regression model, headache exacerbation was no longer an independent predictor of treatment outcome (OR 0.65, 95% CI 0.28 1.51). Factors that independently predicted outcome were nausea (OR 0.12, 95% CI 0.02-1.00, p = 0.05), age (OR 1.68 for each decade increase in age, 95% CI 1.24 2.28), and medication overuse (OR 0.42, 95% CI 0.18-0.97). CONCLUSIONS: After controlling for nausea and other factors, headache exacerbation with DHE infusions is not an independent predictor of poor headache outcome and clinicians should not interpret its presence as a reason to stop treatment. The focus of management should be on controlling nausea as it is the most important modifiable factor in achieving a good headache outcome with an inpatient course of IV DHE for chronic migraine. PMID- 26843570 TI - Keep Your Scanners Peeled: Gaze Behavior as a Measure of Automation Trust During Highly Automated Driving. AB - OBJECTIVE: The feasibility of measuring drivers' automation trust via gaze behavior during highly automated driving was assessed with eye tracking and validated with self-reported automation trust in a driving simulator study. BACKGROUND: Earlier research from other domains indicates that drivers' automation trust might be inferred from gaze behavior, such as monitoring frequency. METHOD: The gaze behavior and self-reported automation trust of 35 participants attending to a visually demanding non-driving-related task (NDRT) during highly automated driving was evaluated. The relationship between dispositional, situational, and learned automation trust with gaze behavior was compared. RESULTS: Overall, there was a consistent relationship between drivers' automation trust and gaze behavior. Participants reporting higher automation trust tended to monitor the automation less frequently. Further analyses revealed that higher automation trust was associated with lower monitoring frequency of the automation during NDRTs, and an increase in trust over the experimental session was connected with a decrease in monitoring frequency. CONCLUSION: We suggest that (a) the current results indicate a negative relationship between drivers' self-reported automation trust and monitoring frequency, (b) gaze behavior provides a more direct measure of automation trust than other behavioral measures, and (c) with further refinement, drivers' automation trust during highly automated driving might be inferred from gaze behavior. APPLICATION: Potential applications of this research include the estimation of drivers' automation trust and reliance during highly automated driving. PMID- 26843572 TI - Pharmacoepidemiological comparisons between acenocoumarol and dabigatran: interpretation of data reflecting clinical practice. PMID- 26843571 TI - Effectiveness and safety of dabigatran versus acenocoumarol in 'real-world' patients with atrial fibrillation. AB - AIMS: Randomized trials showed non-inferior or superior results of the non vitamin-K-antagonist oral anticoagulants (NOACs) compared with warfarin. The aim of this study was to assess the effectiveness and safety of dabigatran (direct thrombin inhibitor) vs. acenocoumarol (vitamin K antagonist) in patients with atrial fibrillation (AF) in daily clinical practice. METHODS AND RESULTS: In this observational study, we evaluated all consecutive patients who started anticoagulation because of AF in our outpatient clinic from 2010 to 2013. Data were collected from electronic patient charts. Primary outcomes were stroke or systemic embolism and major bleeding. Propensity score matching was applied to address the non-randomized design. In total, 920 consecutive AF patients were enrolled (442 dabigatran, 478 acenocoumarol), of which 2 * 383 were available for analysis after propensity score matching. Mean follow-up duration was 1.5 +/- 0.56 year. The mean calculated stroke risk according to the CHA2DS2-VASc score was 3.5%/year in dabigatran vs. 3.7%/year acenocoumarol-treated patients. The actual incidence rate of stroke or systemic embolism was 0.8%/year [95% confidence interval (CI): 0.2-2.1] vs. 1.0%/year (95% CI: 0.4-2.1), respectively. Multivariable analysis confirmed this lower but non-significant risk in dabigatran vs. acenocoumarol after adjustment for the CHA2DS2-VASc score [hazard ratio (HR)dabigatran = 0.72, 95% CI: 0.20-2.63, P = 0.61]. According to the HAS BLED score, the mean calculated bleeding risk was 1.7%/year in both groups. Actual incidence rate of major bleeding was 2.1%/year (95% CI: 1.0-3.8) in the dabigatran vs. 4.3%/year (95% CI: 2.9-6.2) in acenocoumarol. This over 50% reduction remained significant after adjustment for the HAS-BLED score (HRdabigatran = 0.45, 95% CI: 0.22-0.93, P = 0.031). CONCLUSION: In 'real-world' patients with AF, dabigatran appears to be as effective, but significantly safer than acenocoumarol. PMID- 26843573 TI - Stakeholders in non-Vitamin K antagonist oral anticoagulants prescription: the case of Italy. PMID- 26843574 TI - Thoracoscopic epicardial left atrial ablation in symptomatic patients with atrial fibrillation. AB - AIMS: The low efficacy rates reported for conventional catheter ablation of longstanding persistent atrial fibrillation (LPAF) have led to the development of alternative techniques such as minimal invasive surgical ablation, aiming for durable and contiguous transmural lesions. The aim was to evaluate the efficacy and safety of total thoracoscopic epicardial left atrial ablation (TELA-AF) procedures in a prospective study of severely symptomatic patients with either drug-resistant AF and/or failed attempts of catheter ablation. METHODS AND RESULTS: The TELA-AF surgical technique includes pulmonary vein isolation, left atrial (LA) 'box lesion', and partial vagal denervation. The LA appendage was excluded if deemed safe. Patients were followed with clinical evaluations and 12 lead electrocardiograms at 3, 6, and 12 months after the surgical intervention, complemented with a 7-day Holter monitoring after 6 and 12 months. Sixty patients, of whom 38 (63%) suffered from LPAF, underwent TELA-AF between November 2008 and December 2010. One patient with LPAF was lost to follow-up. At 12-month follow-up, 55/59 patients (93%) were free from atrial fibrillation (AF), while 7/59 patients (12%) suffered from recurrent LA tachycardia. Among patients with LPAF, 32/37 (86%) maintained sinus rhythm after 12 months. Adverse events included four perioperative bleedings requiring conversion to sternotomy in three cases, two ischaemic strokes and one transient ischaemic attack. CONCLUSION: The total thoracoscopic surgical ablation procedure is highly effective even in patients with LPAF, and it seems safe. The high rate of iatrogenic LA re-entrant tachycardia, however, warrants further improvement of the technique. PMID- 26843575 TI - The electrocardiographic characteristics of septal flash in patients with left bundle branch block. AB - AIMS: In patients with systolic heart failure and left bundle branch block (LBBB), septal flash (SF) movement has been described by echocardiography. We evaluated the prevalence of SF in LBBB and non-LBBB patients and evaluated whether specific electrocardiographic (ECG) characteristics within LBBB are associated with the presence of SF on echocardiography. METHODS AND RESULTS: One hundred and four patients with probable LBBB on standard 12-lead ECG were selected, 40 patients with non-LBBB served as controls. Left bundle branch block and non-LBBB were defined, according to the most recent guidelines. The presence of SF was assessed by echocardiography. Strict LBBB criteria were met in 93.3% of the patients. Septal flash was present in 45.2% of LBBB patients and was not present in non-LBBB patients. This was more prevalent in patients without anterior ischaemic cardiomyopathy (ICMP) compared with those with anterior ICMP (P = 0.008). The duration of QRS was longer in SF patients compared with that of non-SF patients (P < 0.05). The presence of a mid-QRS notching in more than two consecutive leads was a good predictor for the presence of SF (P = 0.01), and when combined with an absent R-wave in lead V1, the presence of SF is very likely (P = 0.001). CONCLUSION: Our data show that SF is present in 45.2% of LBBB patients, whereas it was absent in patients with non-LBBB. Patients with SF fulfilled more LBBB criteria compared with LBBB patients without SF. Our findings raise the provocative question of whether the presence of SF identifies patients with 'true LBBB' and whether this echocardiographic finding might be considered as a selection parameter in cardiac resynchronization therapy. PMID- 26843576 TI - Stakeholders in NOACs prescription: authors' reply. PMID- 26843577 TI - Combining an subcutaneous ICD and a pacemaker with abdominal device location and bipolar epicardial left ventricular lead: first-in-man approach. PMID- 26843579 TI - Tim Bartness (1953-2015). PMID- 26843580 TI - Proton channels and renal hypertensive injury: a key piece of the Dahl salt sensitive rat puzzle? AB - Hv1 is a voltage-gated proton channel highly expressed in phagocytic cells, where it participates in the NADPH oxidase-dependent respiratory burst. We have recently identified Hv1 as a novel renal channel, expressed in the renal medullary thick ascending limb that appears to importantly contribute to the pathogenesis of renal hypertensive injury in the Dahl salt-sensitive rat model. The purpose of this review is to describe the experimental approaches that we have undertaken to identify the source of excess reactive oxygen species production in the renal outer medulla of Dahl salt-sensitive rats and the resulting evidence that the voltage-gated proton channel Hv1 mediates augmented superoxide production and contributes to renal medullary oxidative stress and renal injury. In addition, we will attempt to point out areas of current controversy, as well as propose areas in which further experimental studies are likely to move the field forward. The content of the following review was presented as part of the Water and Electrolyte Homeostasis Section New Investigator Award talk at Experimental Biology 2014. PMID- 26843582 TI - Electrical stimulation of the aortic depressor nerve in conscious rats overcomes the attenuation of the baroreflex in chronic heart failure. AB - Chronic heart failure (CHF) is characterized by autonomic dysfunction combined with baroreflex attenuation. The hypotensive and bradycardic responses produced by electrical stimulation of the aortic depressor nerve (ADN) were examined in conscious CHF and control male Wistar rats (12-13 wk old). Furthermore, the role of parasympathetic and sympathetic nervous system in mediating the cardiovascular responses to baroreflex activation was evaluated by selective beta1-adrenergic and muscarinic receptor antagonists. CHF was induced by myocardial infarction. After 6 wk, the subjects were implanted with electrodes for ADN stimulation. Twenty-four hours later, electrical stimulation of the ADN was applied for 20 s using five different frequencies (5, 15, 30, 60, and 90 Hz), while the arterial pressure was recorded by a catheter implanted into the femoral artery. Electrical stimulation of the ADN elicited progressive and similar hypotensive and bradycardic responses in control (n = 12) and CHF (n = 11) rats, while the hypotensive response was not affected by methylatropine. Nevertheless, the reflex bradycardia was attenuated by methylatropine in control, but not in CHF rats. Atenolol did not affect the hypotensive or bradycardic response in either group. The ADN function was examined under anesthesia through electroneurographic recordings. The arterial pressure-ADN activity relationship was attenuated in CHF rats. In conclusion, despite the attenuation of baroreceptor function in CHF rats, the electrical stimulation of the ADN elicited a stimulus-dependent hypotension and bradycardia of similar magnitude as observed in control rats. Therefore, electrical activation of the aortic baroreflex overcomes both the attenuation of parasympathetic function and the sympathetic overdrive. PMID- 26843581 TI - Genetic and pharmacological evidence for low-abundance TRPV3 expression in primary vagal afferent neurons. AB - Primary vagal afferent neurons express a multitude of thermosensitive ion channels. Within this family of ion channels, the heat-sensitive capsaicin receptor (TRPV1) greatly influences vagal afferent signaling by determining the threshold for action-potential initiation at the peripheral endings, while controlling temperature-sensitive forms of glutamate release at central vagal terminals. Genetic deletion of TRPV1 does not completely eliminate these temperature-dependent effects, suggesting involvement of additional thermosensitive ion channels. The warm-sensitive, calcium-permeable, ion channel TRPV3 is commonly expressed with TRPV1; however, the extent to which TRPV3 is found in vagal afferent neurons is unknown. Here, we begin to characterize the genetic and functional expression of TRPV3 in vagal afferent neurons using molecular biology (RT-PCR and RT-quantitative PCR) in whole nodose and isolated neurons and fluorescent calcium imaging on primary cultures of nodose ganglia neurons. We confirmed low-level TRPV3 expression in vagal afferent neurons and observed direct activation with putative TRPV3 agonists eugenol, ethyl vanillin (EVA), and farnesyl pyrophosphate (FPP). Agonist activation stimulated neurons also containing TRPV1 and was blocked by ruthenium red. FPP sensitivity overlapped with EVA and eugenol but represented the smallest percentage of vagal afferent neurons, and it was the only agonist that did not stimulate neurons from TRPV3(-/-1) mice, suggesting FPP has the highest selectivity. Further, FPP was predictive of enhanced responses to capsaicin, EVA, and eugenol in rats. From our results, we conclude TRPV3 is expressed in a discrete subpopulation of vagal afferent neurons and may contribute to vagal afferent signaling either directly or in combination with TRPV1. PMID- 26843583 TI - Dive, food, and exercise effects on blood microparticles in Steller sea lions (Eumetopias jubatus): exploring a biomarker for decompression sickness. AB - Recent studies of stranded marine mammals indicate that exposure to underwater military sonar may induce pathophysiological responses consistent with decompression sickness (DCS). However, DCS has been difficult to diagnose in marine mammals. We investigated whether blood microparticles (MPs, measured as number/MUl plasma), which increase in response to decompression stress in terrestrial mammals, are a suitable biomarker for DCS in marine mammals. We obtained blood samples from trained Steller sea lions (Eumetopias jubatus, 4 adult females) wearing time-depth recorders that dove to predetermined depths (either 5 or 50 meters). We hypothesized that MPs would be positively related to decompression stress (depth and duration underwater). We also tested the effect of feeding and exercise in isolation on MPs using the same blood sampling protocol. We found that feeding and exercise had no effect on blood MP levels, but that diving caused MPs to increase. However, blood MP levels did not correlate with diving depth, relative time underwater, and presumed decompression stress, possibly indicating acclimation following repeated exposure to depth. PMID- 26843584 TI - Catheter ablation of atrial fibrillation in patients with heart failure: impact of maintaining sinus rhythm on heart failure status and long-term rates of stroke and death. AB - AIMS: Catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) can improve left ventricular (LV) function and HF symptoms. We aimed to investigate whether long-term maintenance of sinus rhythm impacts on hard outcomes such as stroke and death. METHODS AND RESULTS: An international multicentre registry was compiled from seven centres for consecutive patients undergoing catheter ablation of AF. Long-term freedom from AF was examined in patients with and without HF. The impact of maintaining sinus rhythm on rates of stroke and death was also examined. A total of 1273 patients were included: 171 with HF and 1102 without. Median follow-up was 3.1 years (IQR 2.0-4.3). The final procedure success rate was no different for paroxysmal AF (PAF) (78.7 vs. 85.7%, P = 0.186), but significantly different for persistent AF (57.3 vs. 75.8%, P < 0.001). Multivariate analysis showed that HF independently predicted recurrent arrhythmia [hazard ratio (HR) 1.7, 95% confidence interval (CI) 1.2-2.4, P = 0.002]. New York Heart Association class decreased from 2.3 +/- 0.7 at baseline to 1.5 +/- 0.8 at follow-up (P < 0.001). Left ventricular ejection fraction (LVEF) increased from 34.3 +/- 9.0 to 45.8 +/- 12.8% (P < 0.001). Recurrent AF was strongly predictive of stroke or death in HF patients (HR 8.33, 95% CI 1.86 37.7, P = 0.001). CONCLUSION: Long-term success rates for persistent (but not paroxysmal) AF ablation are significantly lower in HF patients. Left ventricular function and HF symptoms were improved following ablation. In HF patients, recurrent arrhythmia strongly predicted stroke and death during follow-up. PMID- 26843585 TI - The Colonic Microbiome and Epithelial Transcriptome Are Altered in Rats Fed a High-Protein Diet Compared with a Normal-Protein Diet. AB - BACKGROUND: A high-protein diet (HPD) can produce hazardous compounds and reduce butyrate-producing bacteria in feces, which may be detrimental to gut health. However, information on whether HPD affects intestinal function is limited. OBJECTIVE: The aim of this study was to determine the impact of an HPD on the microbiota, microbial metabolites, and epithelial transcriptome in the colons of rats. METHODS: Adult male Wistar rats were fed either a normal-protein diet (20% protein, 56% carbohydrate) or an HPD (45% protein, 30% carbohydrate) for 6 wk (n = 10 rats per group, individually fed). After 6 wk, the colonic microbiome, microbial metabolites, and epithelial transcriptome were determined. RESULTS: Compared with the normal-protein diet, the HPD adversely altered the colonic microbiota by increasing (P < 0.05) Escherichia/Shigella, Enterococcus, Streptococcus, and sulfate-reducing bacteria by 54.9-fold, 31.3-fold, 5.36-fold, and 2.59-fold, respectively. However, the HPD reduced Ruminococcus (8.04-fold), Akkermansia (not detected in HPD group), and Faecalibacterium prausnitzii (3.5 fold) (P < 0.05), which are generally regarded as beneficial bacteria in the colon. Concomitant increases in cadaverine (4.88-fold), spermine (31.2-fold), and sulfide (4.8-fold) (P < 0.05) and a decrease in butyrate (2.16-fold) (P < 0.05) in the HPD rats indicated an evident shift toward the production of unhealthy microbial metabolites. In the colon epithelium of the HPD rats, transcriptome analysis identified an upregulation of genes (P < 0.05) involved in disease pathogenesis; these genes are involved in chemotaxis, the tumor necrosis factor signal process, and apoptosis. The HPD was also associated with a downregulation of many genes (P < 0.05) involved in immunoprotection, such as genes involved in innate immunity, O-linked glycosylation of mucin, and oxidative phosphorylation, suggesting there may be an increased disease risk in these rats. The abundance of Escherichia/Shigella, Enterococcus, and Streptococcus was positively correlated (Spearman's rho > 0.7, P < 0.05) with genes and metabolites generally regarded as being involved in disease pathogenesis, suggesting these bacteria may mediate the detrimental effects of HPDs on colonic health. CONCLUSION: Our findings suggest that the HPD altered the colonic microbial community, shifted the metabolic profile, and affected the host response in the colons of rats toward an increased risk of colonic disease. PMID- 26843586 TI - Common Phenolic Metabolites of Flavonoids, but Not Their Unmetabolized Precursors, Reduce the Secretion of Vascular Cellular Adhesion Molecules by Human Endothelial Cells. AB - BACKGROUND: Flavonoids have been implicated in the prevention of cardiovascular disease; however, their mechanisms of action have yet to be elucidated, possibly because most previous in vitro studies have used supraphysiological concentrations of unmetabolized flavonoids, overlooking their more bioavailable phenolic metabolites. OBJECTIVE: We aimed to explore the effects of phenolic metabolites and their precursor flavonoids at physiologically achievable concentrations, in isolation and combination, on soluble vascular cellular adhesion molecule-1 (sVCAM-1). METHOD: Fourteen phenolic acid metabolites and 6 flavonoids were screened at 1 MUM for their relative effects on sVCAM-1 secretion by human umbilical vein endothelial cells stimulated with tumor necrosis factor alpha (TNF-alpha). The active metabolites were further studied for their response at different concentrations (0.01 MUM-100 MUM), structure-activity relationships, and effect on vascular cellular adhesion molecule (VCAM)-1 mRNA expression. In addition, the additive activity of the metabolites and flavonoids was investigated by screening 25 unique mixtures at cumulative equimolar concentrations of 1 MUM. RESULTS: Of the 20 compounds screened at 1 MUM, inhibition of sVCAM-1 secretion was elicited by 4 phenolic metabolites, of which protocatechuic acid (PCA) was the most active (-17.2%, P = 0.05). Investigations into their responses at different concentrations showed that PCA significantly reduced sVCAM-1 15.2-36.5% between 1 and 100 MUM, protocatechuic acid-3-sulfate and isovanillic acid reduced sVCAM-1 levels 12.2-54.7% between 10 and 100 MUM, and protocatechuic acid-4-sulfate and isovanillic acid-3-glucuronide reduced sVCAM-1 secretion 27.6% and 42.8%, respectively, only at 100 MUM. PCA demonstrated the strongest protein response and was therefore explored for its effect on VCAM-1 mRNA, where 78.4% inhibition was observed only after treatment with 100 MUM PCA. Mixtures of the metabolites showed no activity toward sVCAM-1, suggesting no additive activity at 1 MUM. CONCLUSIONS: The present findings suggest that metabolism of flavonoids increases their vascular efficacy, resulting in a diversity of structures of varying bioactivity in human endothelial cells. PMID- 26843588 TI - Coffee Consumption Increases the Antioxidant Capacity of Plasma and Has No Effect on the Lipid Profile or Vascular Function in Healthy Adults in a Randomized Controlled Trial. AB - BACKGROUND: Coffee, a source of antioxidants, has controversial effects on cardiovascular health. OBJECTIVE: We evaluated the bioavailability of chlorogenic acids (CGAs) in 2 coffees and the effects of their consumption on the plasma antioxidant capacity (AC), the serum lipid profile, and the vascular function in healthy adults. METHODS: Thirty-eight men and 37 women with a mean +/- SD age of 38.5 +/- 9 y and body mass index of 24.1 +/- 2.6 kg/m(2) were randomly assigned to 3 groups: a control group that did not consume coffee or a placebo and 2 groups that consumed 400 mL coffee/d for 8 wk containing a medium (MCCGA; 420 mg) or high (HCCGA; 780 mg) CGA content. Both were low in diterpenes (0.83 mg/d) and caffeine (193 mg/d). Plasma caffeic and ferulic acid concentrations were measured by GC, and the plasma AC was evaluated with use of the ferric-reducing antioxidant power method. The serum lipid profile, nitric oxide (NO) plasma metabolites, vascular endothelial function (flow-mediated dilation; FMD), and blood pressure (BP) were evaluated. RESULTS: After coffee consumption (1 h and 8 wk), caffeic and ferulic acid concentrations increased in the coffee-drinking groups, although the values of the 2 groups were significantly different (P < 0.001); caffeic and ferulic acid concentrations were undetectable in the control group. At 1 h after consumption, the plasma AC in the control group was significantly lower than the baseline value (-2%) and significantly increased in the MCCGA (6%) and HCCGA (5%) groups (P < 0.05). After 8 wk, no significant differences in the lipid, FMD, BP, or NO plasma metabolite values were observed between the groups. CONCLUSIONS: Both coffees, which contained CGAs and were low in diterpenes and caffeine, provided bioavailable CGAs and had a positive acute effect on the plasma AC in healthy adults and no effect on blood lipids or vascular function. The group that did not drink coffee showed no improvement in serum lipid profile, FMD, BP, or NO plasma metabolites. This trial was registered at registroclinico.sld.cu as RPCEC00000168. PMID- 26843587 TI - Biomarkers of Dietary Intake Are Correlated with Corresponding Measures from Repeated Dietary Recalls and Food-Frequency Questionnaires in the Adventist Health Study-2. AB - BACKGROUND: Accurate assessment of diet in study populations is still a challenge. Some statistical strategies that use biomarkers of dietary intake attempt to compensate for the biasing effects of reporting errors. OBJECTIVE: The objective was to correlate biomarkers of dietary intake with 2 direct measures of dietary intake. METHODS: Subjects provided repeated 24-h dietary recalls and 2 food-frequency questionnaires (FFQs) separated by ~3 y. Correlations between biomarkers and reported dietary intakes as measured by the recalls and FFQs were de-attenuated for within-person variability. The Adventist Health Study-2 (AHS-2) has a large database of biomarkers of dietary intake (blood, urine, adipose tissue) from a calibration study (909 analytic subjects) representing the cohort. Participants were black and non-black Adventists in the United States and Canada. RESULTS: Dietary items with higher-valued de-attenuated correlations (>=0.50) between biomarkers and recalls included some fatty acids (FAs), the non-fish meats, fruit (non-black subjects), some carotenoids, vitamin B-12 (non-black subjects), and vitamin E. Moderately valued correlations (0.30-0.49) were found for very long chain omega-3 (n-3) FAs, some carotenoids, folate, isoflavones, cruciferous vegetables, fruit (black subjects), and calcium. The highest correlation values in non-black and black subjects were 0.69 (urinary 1-methyl histidine and meat consumption) and 0.72 (adipose and dietary 18:2 omega-6), respectively. Correlations comparing biomarkers with recalls were generally similar for black and non-black subjects, but correlations between biomarkers and the FFQ were slightly lower than corresponding recall correlations. Correlations between biomarkers and a single FFQ estimate (the usual cohort situation) were generally much lower. CONCLUSIONS: Many biomarkers that have relatively high valued correlations with dietary intake were identified and were usually of similar value in black and non-black subjects. These may be used to correct effects of dietary measurement errors in the AHS-2 cohort, and in some cases they also provide evidence supporting the validity of the dietary data. PMID- 26843590 TI - Young People and Drugs: a Better Long Term Strategy is Needed. PMID- 26843589 TI - Early Life Growth Predicts Pubertal Development in South African Adolescents. AB - BACKGROUND: Given global trends toward earlier onset of puberty and the adverse psychosocial consequences of early puberty, it is important to understand the childhood predictors of pubertal timing and tempo. OBJECTIVE: We examined the association between early growth and the timing and tempo of puberty in adolescents in South Africa. METHODS: We analyzed prospectively collected data from 1060 boys and 1135 girls participating in the Birth-to-Twenty cohort in Soweto, South Africa. Height-for-age z scores (HAZs) and body mass index-for-age z scores (BMIZs) were calculated based on height (centimeters) and body mass index (kilograms per meter squared) at ages 5 y and 8 y. The development of genitals, breasts, and pubic hair was recorded annually from 9 to 16 y of age with the use of the Tanner sexual maturation scale (SMS). We used latent class growth analysis to identify pubertal trajectory classes and also characterized children as fast or slow developers based on the SMS score at 12 y of age. We used multinomial logistic regression to estimate associations of HAZ and BMIZ at ages 5 and 8 y with pubertal development. RESULTS: We identified 3 classes for pubic hair development (for both girls and boys) and 4 classes for breast (for girls) and genital (for boys) development. In girls, both HAZ and BMIZ at age 5 y were positively associated with pubic hair development [relative risk ratio (RRR): 1.57, P < 0.001 and RRR: 1.51, P < 0.01, respectively], as was BMI at age 8 y (RRR: 2.06, P = 0.03); similar findings were observed for breast development. In boys, HAZ and BMIZ at age 5 y were positively associated with pubic hair development (RRR: 1.78, P < 0.001 and RRR: 1.43, P < 0.01, respectively); HAZ at age 5 y was associated with development of genitals (RRR: 2.19, P < 0.01). CONCLUSION: In boys and girls, both height and body mass index in early childhood predicted the trajectory of pubertal development. This may provide a tool to identify children at risk of early pubertal onset. PMID- 26843591 TI - Pain Psychology: "Psychosomatic Medicine, Behavioral Medicine, Just Plain Medicine". PMID- 26843592 TI - Building Capacity in Pain Medicine: The Novel Use of Group Assessment Methods to Enhance Patient Access to Care. PMID- 26843593 TI - A Study of the Reliability and Concurrent Validity of the Chinese Version of the Pain Medication Attitude Questionnaire (ChPMAQ) in a Sample of Chinese Patients with Chronic Pain. AB - OBJECTIVES: The Pain Medication Attitude Questionnaire (PMAQ) was designed to assess concerns about pain medication among patients with chronic nonmalignant pain. The instrument has been demonstrated to be a reliable measure with good psychometric properties, yet its validity among Chinese has not been evaluated. This study aimed to translate the English-language version of the PMAQ into Chinese (ChPMAQ) and to evaluate its reliability and concurrent validity. METHODS: A total of 201 Chinese patients with chronic pain attending two multidisciplinary pain clinics in Hong Kong completed the ChPMAQ, the Chronic Pain Grade (CPG) questionnaire, the mental health subscale of the SF-12 (QoL Mental), and questions assessing sociodemographic and pain characteristics. RESULTS: Our results showed that the seven ChPMAQ scales possessed good internal consistency. Except for the correlation between Withdrawal and Mistrust (r = 0.13), all ChPMAQ scales were significantly correlated with each other (all p < 0.01). The scales also correlated with two concurrent criterion measures, QoL Mental and Pain Disability, in a predictable direction. Results of hierarchical multiple regression analyses showed that the ChPMAQ scales predicted concurrent QoL-Mental (F(7,190) = 2.75, p < 0.05) and pain disability (F(7,188) = 3.00, p < 0.01). Need (std beta = -0.23, p<0.05) and Side effects (std beta = 0.27, p < 0.01) emerged as independent predictors of concurrent QoL-Mental and pain disability, respectively. CONCLUSION: Despite the current preliminary findings for the reliability and concurrent validity of the ChPMAQ, more research is needed to substantiate the reliability, validity and other psychometric properties of the instrument. PMID- 26843594 TI - A Rare Cause of Back Pain During Pregnancy and Lactation: Management and Treatment. PMID- 26843595 TI - Pooled, but not single-neuron, responses in macaque V4 represent a solution to the stereo correspondence problem. AB - Binocular disparity is an important cue for depth perception. To correctly represent disparity, neurons must find corresponding visual features between the left- and right-eye images. The visual pathway ascending from V1 to inferior temporal cortex solves the correspondence problem. An intermediate area, V4, has been proposed to be a critical stage in the correspondence process. However, the distinction between V1 and V4 is unclear, because accumulating evidence suggests that the process begins within V1. In this article, we report that the pooled responses in macaque V4, but not responses of individual neurons, represent a solution to the correspondence problem. We recorded single-unit responses of V4 neurons to random-dot stereograms of varying degrees of anticorrelation. To achieve gradual anticorrelation, we reversed the contrast of an increasing proportion of dots as in our previous psychophysical studies, which predicted that the neural correlates of the solution to correspondence problem should gradually eliminate their disparity modulation as the level of anticorrelation increases. Inconsistent with this prediction, the tuning amplitudes of individual V4 neurons quickly decreased to a nonzero baseline with small anticorrelation. By contrast, the shapes of individual tuning curves changed more gradually so that the amplitude of population-pooled responses gradually decreased toward zero over the entire range of graded anticorrelation. We explain these results by combining multiple energy-model subunits. From a comparison with the population-pooled responses in V1, we suggest that disparity representation in V4 is distinctly advanced from that in V1. Population readout of V4 responses provides disparity information consistent with the correspondence solution. PMID- 26843596 TI - Interleukin-1beta activates an Src family kinase to stimulate the plasma membrane Ca2+ pump in hippocampal neurons. AB - The plasma membrane Ca(2+) ATPase (PMCA) plays a major role in clearing Ca(2+) from the neuronal cytoplasm. The cytoplasmic Ca(2+) clearance rate affects neuronal excitability, synaptic plasticity, and neurotransmission. Here, we examined the modulation of PMCA activity by PTKs in hippocampal neurons. PMCA mediated Ca(2+) clearance slowed in the presence of pyrazolopyrimidine 2, an inhibitor of Src family kinases (SFKs), and accelerated in the presence of C2 ceramide, an activator of PTKs. Ca(2+) clearance kinetics were attenuated in cells expressing a dominant-negative Src mutant, suggesting that the pump is tonically stimulated by a PTK. Tonic stimulation was reduced in hippocampal neurons expressing short hairpin (sh)RNA directed to mRNA for Yes. shRNA-mediated knockdown of PMCA isoform 1 (PMCA1) removed tonic stimulation of Ca(2+) clearance, indicating that the kinase stimulates PMCA1. IL-1beta accelerated Ca(2+) clearance in a manner blocked by an IL-1beta receptor antagonist or by an inhibitor of neutral sphingomyelinase, the enzyme that produces ceramide. Thus IL 1beta activates an SFK to stimulate the plasma membrane Ca(2+) pump, decreasing the duration of Ca(2+) transients in hippocampal neurons. PMID- 26843597 TI - Perceiving and acting upon weight illusions in the absence of somatosensory information. AB - When lifting novel objects, individuals' fingertip forces are influenced by a variety of cues such as volume and apparent material. This means that heavy looking objects tend to be lifted with more force than lighter-looking objects, even when they weigh the same amount as one another. Expectations about object weight based on visual appearance also influence how heavy an object feels when it is lifted. For instance, in the "size-weight illusion," small objects feel heavier than equally weighted large objects. Similarly, in the "material-weight illusion," objects that seem to be made from light-looking materials feel heavier than objects of the same weight that appear to be made from heavy-looking materials. In this study, we investigated these perceptual and sensorimotor effects in IW, an individual with peripheral deafferentation (i.e., a loss of tactile and proprioception feedback). We examined his perceptions of heaviness and fingertip force application over repeated lifts of objects that varied in size or material properties. Despite being able to report real weight differences, IW did not appear to experience the size- or material-weight illusions. Furthermore, he showed no evidence of sensorimotor prediction based on size and material cues. The results are discussed in the context of forward models and their possible influence on weight perception and fingertip force control. PMID- 26843598 TI - Frequency-selective transmission of graded signals in large monopolar neurons of blowfly Calliphora vicina compound eye. AB - The functional roles of voltage-gated K(+)(Kv) channels in visual system interneurons remain poorly studied. We have addressed this problem in the large monopolar cells (LMCs) of the blowfly Calliphora vicina, using intracellular recordings and mathematical modeling methods. Intracellular recordings were performed in two cellular compartments: the synaptic zone, which receives input from photoreceptors, and the axon, which provides graded potential output to the third-order visual neurons. Biophysical properties of Kv conductances in the physiological voltage range were examined in the dark with injections of current in the discontinuous current-clamp mode. Putative LMC types 1/2 and 3 (L1/2 and L3, respectively) had dissimilar Kv channelomes: L1/2 displayed a prominent inactivating Kv conductance in the axon, while L3 cells were characterized by a sustained delayed-rectifier Kv conductance. To study the propagation of voltage signals, the data were incorporated into the previously developed mathematical model. We demonstrate that the complex interaction between the passive membrane properties, Kv conductances, and the neuronal geometry leads to a resonance-like filtering of signals with peak frequencies of transmission near 15 and 40 Hz for L3 and L1/2, respectively. These results point to distinct physiological roles of different types of LMCs. PMID- 26843600 TI - Neural timing signal for precise tactile timing judgments. AB - The brain can precisely encode the temporal relationship between tactile inputs. While behavioural studies have demonstrated precise interfinger temporal judgments, the underlying neural mechanism remains unknown. Computationally, two kinds of neural responses can act as the information source. One is the phase locked response to the phase of relatively slow inputs, and the other is the response to the amplitude change of relatively fast inputs. To isolate the contributions of these components, we measured performance of a synchrony judgment task for sine wave and amplitude-modulation (AM) wave stimuli. The sine wave stimulus was a low-frequency sinusoid, with the phase shifted in the asynchronous stimulus. The AM wave stimulus was a low-frequency sinusoidal AM of a 250-Hz carrier, with only the envelope shifted in the asynchronous stimulus. In the experiment, three stimulus pairs, two synchronous ones and one asynchronous one, were sequentially presented to neighboring fingers, and participants were asked to report which one was the asynchronous pair. We found that the asynchrony of AM waves could be detected as precisely as single impulse pair, with the threshold asynchrony being ~20 ms. On the other hand, the asynchrony of sine waves could not be detected at all in the range from 5 to 30 Hz. Our results suggest that the timing signal for tactile judgments is provided not by the stimulus phase information but by the envelope of the response of the high frequency-sensitive Pacini channel (PC), although they do not exclude a possible contribution of the envelope of non-PCs. PMID- 26843599 TI - Neural spike-timing patterns vary with sound shape and periodicity in three auditory cortical fields. AB - Mammals perceive a wide range of temporal cues in natural sounds, and the auditory cortex is essential for their detection and discrimination. The rat primary (A1), ventral (VAF), and caudal suprarhinal (cSRAF) auditory cortical fields have separate thalamocortical pathways that may support unique temporal cue sensitivities. To explore this, we record responses of single neurons in the three fields to variations in envelope shape and modulation frequency of periodic noise sequences. Spike rate, relative synchrony, and first-spike latency metrics have previously been used to quantify neural sensitivities to temporal sound cues; however, such metrics do not measure absolute spike timing of sustained responses to sound shape. To address this, in this study we quantify two forms of spike-timing precision, jitter, and reliability. In all three fields, we find that jitter decreases logarithmically with increase in the basis spline (B spline) cutoff frequency used to shape the sound envelope. In contrast, reliability decreases logarithmically with increase in sound envelope modulation frequency. In A1, jitter and reliability vary independently, whereas in ventral cortical fields, jitter and reliability covary. Jitter time scales increase (A1 < VAF < cSRAF) and modulation frequency upper cutoffs decrease (A1 > VAF > cSRAF) with ventral progression from A1. These results suggest a transition from independent encoding of shape and periodicity sound cues on short time scales in A1 to a joint encoding of these same cues on longer time scales in ventral nonprimary cortices. PMID- 26843601 TI - Weak signal amplification and detection by higher-order sensory neurons. AB - Sensory systems must extract behaviorally relevant information and therefore often exhibit a very high sensitivity. How the nervous system reaches such high sensitivity levels is an outstanding question in neuroscience. Weakly electric fish (Apteronotus leptorhynchus/albifrons) are an excellent model system to address this question because detailed background knowledge is available regarding their behavioral performance and its underlying neuronal substrate. Apteronotus use their electrosense to detect prey objects. Therefore, they must be able to detect electrical signals as low as 1 MUV while using a sensory integration time of <200 ms. How these very weak signals are extracted and amplified by the nervous system is not yet understood. We studied the responses of cells in the early sensory processing areas, namely, the electroreceptor afferents (EAs) and pyramidal cells (PCs) of the electrosensory lobe (ELL), the first-order electrosensory processing area. In agreement with previous work we found that EAs cannot encode very weak signals with a spike count code. However, PCs can encode prey mimic signals by their firing rate, revealing a huge signal amplification between EAs and PCs and also suggesting differences in their stimulus encoding properties. Using a simple leaky integrate-and-fire (LIF) model we predict that the target neurons of PCs in the midbrain torus semicircularis (TS) are able to detect very weak signals. In particular, TS neurons could do so by assuming biologically plausible convergence rates as well as very simple decoding strategies such as temporal integration, threshold crossing, and combining the inputs of PCs. PMID- 26843602 TI - Synaptic refinement during development and its effect on slow-wave activity: a computational study. AB - Recent evidence suggests that synaptic refinement, the reorganization of synapses and connections without significant change in their number or strength, is important for the development of the visual system of juvenile rodents. Other evidence in rodents and humans shows that there is a marked drop in sleep slow wave activity (SWA) during adolescence. Slow waves reflect synchronous transitions of neuronal populations between active and inactive states, and the amount of SWA is influenced by the connection strength and organization of cortical neurons. In this study, we investigated whether synaptic refinement could account for the observed developmental drop in SWA. To this end, we employed a large-scale neural model of primary visual cortex and sections of the thalamus, capable of producing realistic slow waves. In this model, we reorganized intralaminar connections according to experimental data on synaptic refinement: during prerefinement, local connections between neurons were homogenous, whereas in postrefinement, neurons connected preferentially to neurons with similar receptive fields and preferred orientations. Synaptic refinement led to a drop in SWA and to changes in slow-wave morphology, consistent with experimental data. To test whether learning can induce synaptic refinement, intralaminar connections were equipped with spike timing-dependent plasticity. Oriented stimuli were presented during a learning period, followed by homeostatic synaptic renormalization. This led to activity-dependent refinement accompanied again by a decline in SWA. Together, these modeling results show that synaptic refinement can account for developmental changes in SWA. Thus sleep SWA may be used to track noninvasively the reorganization of cortical connections during development. PMID- 26843603 TI - Model systems for studying cellular mechanisms of SCN1A-related epilepsy. AB - Mutations in SCN1A, the gene encoding voltage-gated sodium channel NaV1.1, cause a spectrum of epilepsy disorders that range from genetic epilepsy with febrile seizures plus to catastrophic disorders such as Dravet syndrome. To date, more than 1,250 mutations in SCN1A have been linked to epilepsy. Distinct effects of individual SCN1A mutations on neuronal function are likely to contribute to variation in disease severity and response to treatment in patients. Several model systems have been used to explore seizure genesis in SCN1A epilepsies. In this article we review what has been learned about cellular mechanisms and potential new therapies from these model systems, with a particular emphasis on the novel model system of knock in Drosophila and a look toward the future with expanded use of patient-specific induced pluripotent stem cell-derived neurons. PMID- 26843604 TI - Temporal accuracy of human cortico-cortical interactions. AB - The precision in space and time of interactions among multiple cortical sites was evaluated by examining repeating precise spatiotemporal patterns of instances in which cortical currents showed brief amplitude undulations. The amplitudes of the cortical current dipoles were estimated by applying a variant of synthetic aperture magnetometry to magnetoencephalographic (MEG) recordings of subjects tapping to metric auditory rhythms of drum beats. Brief amplitude undulations were detected in the currents by template matching at a rate of 2-3 per second. Their timing was treated as point processes, and precise spatiotemporal patterns were searched for. By randomly teetering these point processes within a time window W, we estimated the accuracy of the timing of these brief amplitude undulations and compared the results with those obtained by applying the same analysis to traces composed of random numbers. The results demonstrated that the timing accuracy of patterns was better than 3 ms. Successful classification of two different cognitive processes based on these patterns suggests that at least some of the repeating patterns are specific to a cognitive process. PMID- 26843605 TI - Primary motor cortex neurons classified in a postural task predict muscle activation patterns in a reaching task. AB - Primary motor cortex (M1) activity correlates with many motor variables, making it difficult to demonstrate how it participates in motor control. We developed a two-stage process to separate the process of classifying the motor field of M1 neurons from the process of predicting the spatiotemporal patterns of its motor field during reaching. We tested our approach with a neural network model that controlled a two-joint arm to show the statistical relationship between network connectivity and neural activity across different motor tasks. In rhesus monkeys, M1 neurons classified by this method showed preferred reaching directions similar to their associated muscle groups. Importantly, the neural population signals predicted the spatiotemporal dynamics of their associated muscle groups, although a subgroup of atypical neurons reversed their directional preference, suggesting a selective role in antagonist control. These results highlight that M1 provides important details on the spatiotemporal patterns of muscle activity during motor skills such as reaching. PMID- 26843606 TI - Galpha14 subunit-mediated inhibition of voltage-gated Ca2+ and K+ channels via neurokinin-1 receptors in rat celiac-superior mesenteric ganglion neurons. AB - The mechanisms by which G proteins modulate voltage-gated Ca(2+)channel currents (CaV), particularly CaV2.2 and CaV2.3, are voltage dependent (VD) or voltage independent (VI). VD pathways are typically mediated by Galphai/oand GalphaSsubfamilies. On the other hand, VI inhibition modulation is coupled to the Galphaqsubfamily and signaling pathways downstream of phospholipase C stimulation. In most studies, this latter pathway has been shown to be linked to Galphaqand/or Galpha11protein subunits. However, there are no studies that have examined whether natively expressed Galpha14subunits (Galphaqsubfamily member) couple G protein-coupled receptors (GPCR) with CaV2.2 channels. We report that Galpha14subunits functionally couple the substance P (SP)/neurokinin-1 (NK-1) receptor pathway to CaV2.2 channels in acutely dissociated rat celiac-superior mesenteric ganglion (CSMG) neurons. Exposure of CSMG neurons to SP blocked the CaV2.2 currents in a predominantly VD manner that was pertussis toxin and cholera toxin resistant, as well as Galphaq/11independent. However, silencing Galpha14subunits significantly attenuated the SP-mediated Ca(2+)current block. In another set of experiments, exposure of CSMG neurons to SP led to the inhibition of KCNQ K(+)M-currents. The SP-mediated M-current block was significantly reduced in neurons transfected with Galpha14small-interference RNA. Finally, overexpression of the GTP-bound Galphaq/11binding protein RGS2 did not alter the block of M-currents by SP but significantly abolished the oxotremorine methiodide mediated M-current inhibition. Taken together, these results provide evidence of a new Galpha14-coupled signaling pathway that modulates CaV2.2 and M-currents via SP-stimulated NK-1 receptors in CSMG neurons. PMID- 26843607 TI - Neural coding of image structure and contrast polarity of Cartesian, hyperbolic, and polar gratings in the primary and secondary visual cortex of the tree shrew. AB - We comprehensively characterize spiking and visual evoked potential (VEP) activity in tree shrew V1 and V2 using Cartesian, hyperbolic, and polar gratings. Neural selectivity to structure of Cartesian gratings was higher than other grating classes in both visual areas. From V1 to V2, structure selectivity of spiking activity increased, whereas corresponding VEP values tended to decrease, suggesting that single-neuron coding of Cartesian grating attributes improved while the cortical columnar organization of these neurons became less precise from V1 to V2. We observed that neurons in V2 generally exhibited similar selectivity for polar and Cartesian gratings, suggesting that structure of polar like stimuli might be encoded as early as in V2. This hypothesis is supported by the preference shift from V1 to V2 toward polar gratings of higher spatial frequency, consistent with the notion that V2 neurons encode visual scene borders and contours. Neural sensitivity to modulations of polarity of hyperbolic gratings was highest among all grating classes and closely related to the visual receptive field (RF) organization of ON- and OFF-dominated subregions. We show that spatial RF reconstructions depend strongly on grating class, suggesting that intracortical contributions to RF structure are strongest for Cartesian and polar gratings. Hyperbolic gratings tend to recruit least cortical elaboration such that the RF maps are similar to those generated by sparse noise, which most closely approximate feedforward inputs. Our findings complement previous literature in primates, rodents, and carnivores and highlight novel aspects of shape representation and coding occurring in mammalian early visual cortex. PMID- 26843608 TI - Neural correlates of behavioral amplitude modulation sensitivity in the budgerigar midbrain. AB - Amplitude modulation (AM) is a crucial feature of many communication signals, including speech. Whereas average discharge rates in the auditory midbrain correlate with behavioral AM sensitivity in rabbits, the neural bases of AM sensitivity in species with human-like behavioral acuity are unexplored. Here, we used parallel behavioral and neurophysiological experiments to explore the neural (midbrain) bases of AM perception in an avian speech mimic, the budgerigar (Melopsittacus undulatus). Behavioral AM sensitivity was quantified using operant conditioning procedures. Neural AM sensitivity was studied using chronically implanted microelectrodes in awake, unrestrained birds. Average discharge rates of multiunit recording sites in the budgerigar midbrain were insufficient to explain behavioral sensitivity to modulation frequencies <100 Hz for both tone- and noise-carrier stimuli, even with optimal pooling of information across recording sites. Neural envelope synchrony, in contrast, could explain behavioral performance for both carrier types across the full range of modulation frequencies studied (16-512 Hz). The results suggest that envelope synchrony in the budgerigar midbrain may underlie behavioral sensitivity to AM. Behavioral AM sensitivity based on synchrony in the budgerigar, which contrasts with rate correlated behavioral performance in rabbits, raises the possibility that envelope synchrony, rather than average discharge rate, might also underlie AM perception in other species with sensitive AM detection abilities, including humans. These results highlight the importance of synchrony coding of envelope structure in the inferior colliculus. Furthermore, they underscore potential benefits of devices (e.g., midbrain implants) that evoke robust neural synchrony. PMID- 26843609 TI - T-Cell-Mediated Inflammatory Myopathies in HIV-Positive Individuals: A Histologic Study of 19 Cases. AB - T cell-mediated inflammatory myopathies (polymyositis [PM] and inclusion body myositis [IBM]) sometimes arise in conjunction with HIV infection; however, it is not understood whether PM and IBM arising in the context of HIV (HIV-PM and HV IBM) differ from PM and IBM arising sporadically in HIV-negative individuals (sPM and sIBM). Here, we report the largest series of T cell-mediated inflammatory myopathies from HIV-infected patients (19 biopsies from 15 subjects); 5 cases were pathologically classified as PM (HIV-PM) and 14 as IBM (HIV-IBM). As with sporadic cases, quantitative immunohistochemistry for LC3, p62, and TDP-43 showed significantly greater percentage of stained fibers (% FS) in HIV-IBM compared to HIV-PM samples; however, there was no significant difference in % FS for any of the three markers between HIV-associated and sporadic cases. Despite histologic similarities between HIV-IBM and sIBM but in concordance with prior case reports, patients with HIV-IBM were significantly younger at diagnosis than patients with sIBM; in contrast, the mean age of HIV-PM and sPM patients was not significantly different. In summary, HIV-PM and HIV-IBM are morphologically similar to sPM and sIBM; thus, it remains unclear why patients with HIV-IBM, in contrast to patients with sIBM, sometimes show clinical improvement in response to immunosuppressive therapy. PMID- 26843610 TI - Persistent Fever and Skin Lesions Due to Histoplasmosis in a Boy from Rural Nepal. PMID- 26843611 TI - Enteroinvasive Escherichia coli May Account for Uncultured Shigella. PMID- 26843612 TI - In Response. PMID- 26843613 TI - Physalin A exerts anti-tumor activity in non-small cell lung cancer cell lines by suppressing JAK/STAT3 signaling. AB - The signal transducers and activators of transcription 3 (STAT3) signaling pathway plays critical roles in the pathogenesis and progression of various human cancers, including non-small cell lung cancer (NSCLC). In this study, we aimed to evaluate the therapeutic potential of physalin A, a bioactive withanolide derived from Physalis alkekengi var. francheti used in traditional Chinese medicine, was evaluated in human NSCLC cells. Its and determined whether it effect oninhibited both constitutive and induced STAT3 activity, through repressing the phosphorylation levels of JAK2 and JAK3, resulting in anti-proliferation and pro apoptotic effects on NSCLC cells was also determined, and. theThe antitumor effects of physalin A were also validated usingin an in vivo mouse xenograft models of NSCLC cells. Physalin A had anti-proliferative and pro-apoptotic effects in NSCLC cells with constitutively activated STAT3; it also suppressed both constitutive and induced STAT3 activity by modulating the phosphorylation of JAK2 and JAK3. Furthermore, physalin A abrogated the nuclear translocation and transcriptional activity of STAT3, thereby decreasing the expression levels of STAT3, its target genes, such as Bcl-2 and XIAP. Knockdown of STAT3 expression by small interfering RNA (siRNA) significantly enhanced the pro-apoptotic effects of physalin A in NSCLC cells. Moreover, physalin A significantly suppressed tumor xenograft growth. Thus, as an inhibitor of JAK2/3-STAT3 signaling, physalin A, has potent anti-tumor activities, which may facilitate the development of a therapeutic strategy for treating NSCLC. PMID- 26843614 TI - Inactivation of BRCA2 in human cancer cells identifies a subset of tumors with enhanced sensitivity towards death receptor-mediated apoptosis. AB - PURPOSE: DNA repair defects due to detrimental BRCA2-mutations confer increased susceptibility towards DNA interstrand-crosslinking (ICL) agents and define patient subpopulations for individualized genotype-based cancer therapy. However, due to the side effects of these drugs, there is a need to identify additional agents, which could be used alone or in combination with ICL-agents. Therefore, we investigated whether BRCA2-mutations might also increase the sensitivity towards TRAIL-receptors (TRAIL-R)-targeting compounds. EXPERIMENTAL DESIGN: Two independent model systems were applied: a BRCA2 gene knockout and a BRCA2 gene complementation model. The effects of TRAIL-R-targeting compounds and ICL-agents on cell viability, apoptosis and cell cycle distribution were compared in BRCA2 proficient versus-deficient cancer cells in vitro. In addition, the effects of the TRAIL-R2-targeting antibody LBY135 were assessed in vivo using a murine tumor xenograft model. RESULTS: BRCA2-deficient cancer cells displayed an increased sensitivity towards TRAIL-R-targeting agents. These effects exceeded and were mechanistically distinguishable from the well-established effects of ICL-agents. In vitro, ICL-agents expectedly induced an early cell cycle arrest followed by delayed apoptosis, whereas TRAIL-R-targeting compounds caused early apoptosis without prior cell cycle arrest. In vivo, treatment with LBY135 significantly reduced the tumor growth of BRCA2-deficient cancer cells in a xenograft model. CONCLUSIONS: BRCA2 mutations strongly increase the in vitro- and in vivo sensitivity of cancer cells towards TRAIL-R-mediated apoptosis. This effect is mechanistically distinguishable from the well-established ICL-hypersensitivity of BRCA2-deficient cells. Our study thus defines a new genetic subpopulation of cancers susceptible towards TRAIL-R-targeting compounds, which could facilitate novel therapeutic approaches for patients with BRCA2-deficient tumors. PMID- 26843615 TI - The correlation between microRNA490-3p and TGFalpha in endometrial carcinoma tumorigenesis and progression. AB - MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate the translation of messenger RNAs by binding their 3'-untranslated region (3' UTR). MiR-490-3p has been reported to be a suppressor in various human cancers; however, little is known about the biological functions of miR-490-3p in endometrial cancer (EC). In our study, we found that MiR-490-3p mRNA expression was significantly lower in ECs than in normal endometrial tissues. MiR-490-3p mRNA expression was also negatively associated with depth of invasion (mucosa vs. muscular and serosa) and lymph node metastasis (negative vs. positive) in EC. MiR 490-3p overexpression reduced proliferation; promoted G1 arrest and apoptosis; suppressed migration and invasion; and reduced TGFalpha, NF-kB, cyclin D1, survivin, matrix metalloproteinase 2 (MMP2) mRNA and protein expression, and improved Bax mRNA and protein expression. The dual-luciferase reporter assay indicated that miR-490-3p directly targeted TGFalpha by binding its 3' untranslated region. MiR-490-3P transfection also suppressed tumor development and TGFalpha expression (as determined by immunohistochemistry and western blotting) in vivo in the xenograft mouse model. This is the first demonstration that miR-490-3P might act as a suppressor in EC tumorigenesis and progression by targeting TGFalpha. Our results provide a theoretical basis for the further study on the molecular target for endometrial cancer. PMID- 26843616 TI - In vitro and in vivo inhibition of breast cancer cell growth by targeting the Hedgehog/GLI pathway with SMO (GDC-0449) or GLI (GANT-61) inhibitors. AB - Aberrant Hedgehog (Hh)/glioma-associated oncogene (GLI) signaling has been implicated in cancer progression. Here, we analyzed GLI1, Sonic Hedgehog (Shh) and NF-kappaB expression in 51 breast cancer (ductal carcinoma) tissues using immunohistochemistry. We found a positive correlation between nuclear GLI1 expression and tumor grade in ductal carcinoma cases. Cytoplasmic Shh staining significantly correlated with a lower tumor grade. Next, the in vitro effects of two Hh signaling pathway inhibitors on breast cancer cell lines were evaluated using the Smoothened (SMO) antagonist GDC-0449 and the direct GLI1 inhibitor GANT 61. GDC-0449 and GANT-61 exhibited the following effects: a) inhibited breast cancer cell survival; b) induced apoptosis; c) inhibited Hh pathway activity by decreasing the mRNA expression levels of GLI1 and Ptch and inhibiting the nuclear translocation of GLI1; d) increased/decreased EGFR and ErbB2 protein expression, reduced p21-Ras and ERK1/ERK2 MAPK activities and inhibited AKT activation; and e) decreased the nuclear translocation of NF-kappaB. However, GANT-61 exerted these effects more effectively than GDC-0449. The in vivo antitumor activities of GDC-0449 and GANT-61 were analyzed in BALB/c mice that were subcutaneously inoculated with mouse breast cancer (TUBO) cells. GDC-0449 and GANT-61 suppressed tumor growth of TUBO cells in BALB/c mice to different extents. These findings suggest that targeting the Hh pathway using antagonists that act downstream of SMO is a more efficient strategy than using antagonists that act upstream of SMO for interrupting Hh signaling in breast cancer. PMID- 26843617 TI - [68Ga]Pentixafor-PET/CT for imaging of chemokine receptor 4 expression in small cell lung cancer--initial experience. AB - Chemokine receptor CXCR4 is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4 directed imaging of small cell lung cancer (SCLC) with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine ligand [68Ga]Pentixafor. 10 patients with primarily diagnosed (n=3) or pre-treated (n=7) SCLC (n=9) or large cell neuroendocrine carcinoma of the lung (LCNEC, n=1) underwent [68Ga]Pentixafor-PET/CT. 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG, n=6) and/or somatostatin receptor (SSTR)-directed PET/CT with [68Ga]DOTATOC (n=5) and immunohistochemistry (n=10) served as standards of reference. CXCR4-PET was positive in 8/10 patients and revealed more lesions with significantly higher tumor-to-background ratios than SSTR-PET. Two patients who were positive on [18F]FDG-PET were missed by CXCR4-PET, in the remainder [68Ga]Pentixafor detected an equal (n=2) or higher (n=2) number of lesions. CXCR4 expression of tumor lesions could be confirmed by immunohistochemistry. Non-invasive imaging of CXCR4 expression in SCLC is feasible. [68Ga]Pentixafor as a novel PET tracer might serve as readout for confirmation of CXCR4 expression as prerequisite for potential CXCR4-directed treatment including receptor-radio(drug)peptide therapy. PMID- 26843618 TI - Extracorporeal Shock Wave Treatment (ESWT) enhances the in vitro-induced differentiation of human tendon-derived stem/progenitor cells (hTSPCs). AB - Extracorporeal shock wave therapy (ESWT) is a non-invasive and innovative technology for the management of specific tendinopathies. In order to elucidate the ESWT-mediated clinical benefits, human Tendon-derived Stem/Progenitor cells (hTSPCs) explanted from 5 healthy semitendinosus (ST) and 5 ruptured Achilles (AT) tendons were established. While hTSPCs from the two groups showed similar proliferation rates and stem cell surface marker profiles, we found that the clonogenic potential was maintained only in cells derived from healthy donors. Interestingly, ESWT significantly accelerated hTSPCs differentiation, suggesting that the clinical benefits of ESWT may be ascribed to increased efficiency of tendon repair after injury. PMID- 26843620 TI - Depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73-mediated DR5 upregulation. AB - Our previous study revealed that knockdown of CABYR-a/b increases the chemosensitivity of lung cancer cells through inactivation of Akt. Here, we demonstrated that depletion of CABYR-a/b significantly increased DR5 expression and sensitized lung cancer cells to TRAIL-induced apoptosis in vitro and/or in vivo. Importantly, treatment with AD5-10, a DR5-specific agonistic monoclonal antibody, was able to mimic TRAIL-induced apoptosis in CABYR-a/b-silenced cells. Strikingly, we identified that depletion of CABYR-a/b not only increased the expressions of p73 and DR5 but also decreased the phosphorylation of YAP S127. Loss- or gain-of-function studies of YAP and p73 revealed that double deletions of YAP and p73 effectively decreased the expression of DR5 and abolished TRAIL induced apoptosis in CABYR-a/b knockdown cells. Conversely, the co-overexpression of YAP and p73 promoted the expression of DR5 and sensitized cells to TRAIL induced apoptosis. Taken together, our results demonstrate that depletion of CABYR-a/b sensitizes lung cancer cells to TRAIL-induced apoptosis through YAP/p73 mediated DR5 upregulation. PMID- 26843621 TI - The energy sensor AMPK regulates Hedgehog signaling in human cells through a unique Gli1 metabolic checkpoint. AB - Hedgehog signaling controls proliferation of cerebellar granule cell precursors (GCPs) and its aberrant activation is a leading cause of Medulloblastoma, the most frequent pediatric brain tumor. We show here that the energy sensor AMPK inhibits Hh signaling by phosphorylating a single residue of human Gli1 that is not conserved in other species. Studies with selective agonists and genetic deletion have revealed that AMPK activation inhibits canonical Hh signaling in human, but not in mouse cells. Indeed we show that AMPK phosphorylates Gli1 at the unique residue Ser408, which is conserved only in primates but not in other species. Once phosphorylated, Gli1 is targeted for proteasomal degradation. Notably, we show that selective AMPK activation inhibits Gli1-driven proliferation and that this effect is linked to Ser408 phosphorylation, which represents a key metabolic checkpoint for Hh signaling. Collectively, this data unveil a novel mechanism of inhibition of Gli1 function, which is exclusive for human cells and may be exploited for the treatment of Medulloblastoma or other Gli1 driven tumors. PMID- 26843622 TI - A TET2 rs3733609 C/T genotype is associated with predisposition to the myeloproliferative neoplasms harboring JAK2(V617F) and confers a proliferative potential on erythroid lineages. AB - Common germline single-nucleotide polymorphisms (SNPs) at JAK2 locus have been associated with Myeloproliferative neoplasms (MPN). And, the germline sequence variant rs2736100 C in TERT is related to risk of MPN, suggesting a complex association between SNPs and the pathogenesis of MPN. Our previous study (unpublished data) showed that there was a high frequency distribution in rs3733609 C/T genotype at Ten-Eleven Translocation 2 (TET2) locus in one Chinese familial primary myelofibrosis. In the present study, we evaluate the role and clinical significance of rs3733609 C/T genotype in JAK2V617F-positive sporadic MPN (n = 181). TET2 rs3733609 C/T genotype had a higher incidence (13.81%; 25/181) in JAK2V617F-positive sporadic MPN patients than that in normal controls (n = 236) (6.35%; 15/236), which was predisposing to MPN (odds ratio(OR) = 2.361; P = 0.01). MPN patients with rs3733609 C/T genotype had increased leukocyte and platelets counts, elevated hemoglobin concentration in comparison with T/T genotype. Thrombotic events were more common in MPN patients with rs3733609 C/T than those with T/T genotype (P < 0.01). We confirmed that rs3733609 C/T genotype downregulated TET2 mRNA transcription, and the mechanism may be involved in a disruption of the interaction between CCAAT/enhancer binding protein alpha (C/EBPA) and TET2 rs3733609 C/T locus.TET2 rs3733609 C/T genotype stimulated the erythroid hematopoiesis in MPN patients. Altogether, we found a novel hereditary susceptible factor-TET2 rs3733609 C/T variant for the development of MPN, suggesting the variant may be partially responsible for the pathogenesis and accumulation of MPN. PMID- 26843619 TI - Evolving roles of circadian rhythms in liver homeostasis and pathology. AB - Circadian clock in mammals is determined by a core oscillator in the suprachiasmatic nucleus (SCN) of the hypothalamus and synchronized peripheral clocks in other tissues. The coherent timing systems could sustain robust output of circadian rhythms in response to the entrainment controlled environmentally. Disparate approaches have discovered that clock genes and clock-controlled genes (CCGs) exist in nearly all mammalian cell types and are essential for establishing the mechanisms and complexity of internal time-keeping systems. Accumulating evidence demonstrates that the control of homeostasis and pathology in the liver involves intricate loops of transcriptional and post-translational regulation of clock genes expression. This review will focus on the recent advances with great importance concerning clock rhythms linking liver homeostasis and diseases. We particularly highlight what is currently known of the evolving insights into the mechanisms underlying circadian clock . Eventually , findings during recent years in the field might prompt new circadian-related chronotherapeutic strategies for the diagnosis and treatment of liver diseases by coupling these processes. PMID- 26843623 TI - Distinguishing epigenetic features of preneoplastic testis tissues adjacent to seminomas and nonseminomas. AB - PIWI pathway proteins are expressed during spermatogenesis where they play a key role in germ cell development. Epigenetic loss of PIWI proteins expression was previously demonstrated in testicular germ cell tumors (TGCTs), implying their involvement in TGCT development. In this work, apart from studying only normal testis and TGCT samples, we also analyzed an intermediate stage, i.e. preneoplastic testis tissues adjacent to TGCTs. Importantly, in this study, we minimized the contribution of patient-to-patient heterogeneity by using matched preneoplastic/TGCT samples. Surprisingly, expression of germ cell marker DDX4 suggests that spermatogenesis is retained in premalignant testis tissues adjacent to nonseminoma, but not those adjacent to seminoma. Moreover, this pattern is followed by expression of PIWI pathway genes, which impacts one of their functions: DNA methylation level over LINE-1 promoters is higher in preneoplastic testis tissues adjacent to nonseminomas than those adjacent to seminomas. This finding might imply distinct routes for development of the two types of TGCTs and could be used as a novel diagnostic marker, possibly, noninvasively. Finally, we studied the role of CpG island methylation in expression of PIWI genes in patient samples and using in vitro experiments in cell line models: a more complex interrelation between DNA methylation and expression of the corresponding genes was revealed. PMID- 26843627 TI - Remediating Math Anxiety through Cognitive Training: Potential Roles for Math Ability and Social Context. PMID- 26843625 TI - The effects of aging and maternal protein restriction during lactation on thymic involution and peripheral immunosenescence in adult mice. AB - Environmental factors such as nutrition during early life can influence long-term health, a concept termed developmental programming. Initial research was focused towards the effects on metabolic health but more recent studies have demonstrated effects on parameters such as lifespan and immunity. In this study we report that maternal protein restriction during lactation in mice, that is known to prolong lifespan, slows aging of the central and peripheral immune systems. Offspring of dams fed a postnatal low-protein (PLP) diet during lactation had a significant increase in thymic cellularity and T cell numbers across their lifespan compared to controls, and a less marked age-associated decrease in thymocyte cluster of differentiation (CD) 3 expression. PLP animals also demonstrated increased relative splenic cellularity, increased naive: memory CD4+ and CD8+ T cell ratios, increased staining and density of germinal centres, and decreased gene expression of p16 in the spleen, a robust biomarker of aging. A slower rate of splenic aging in PLP animals would be expected to result in decreased susceptibility to infection and neoplasia. In conclusion nutritionally-induced slow postnatal growth leads to delayed aging of the adaptive immune system, which may contribute towards the extended lifespan observed in these animals. PMID- 26843628 TI - Lipid Raft-Excluded GFRalpha1/Ret Fails to Transmit GDNF Signaling In Vivo. PMID- 26843624 TI - Characterization and redox mechanism of asthma in the elderly. AB - Asthma is a chronic disease characterized by reversible airflow limitation, coughing, bronchial constriction, and an inflammatory immune response. While asthma has frequently been categorized as emerging in childhood, evidence has begun to reveal that the elderly population is certainly susceptible to late onset, or even long-standing asthma. Non-atopic asthma, most commonly found in elderly patients is associated with elevated levels of serum and sputum neutrophils and may be more detrimental than atopic asthma. The mortality of asthma is high in the elderly since these patients often possess more severe symptoms than younger populations. The redox mechanisms that mediate inflammatory reactions during asthma have not been thoroughly interpreted in the context of aging. Thus, we review the asthmatic symptoms related to reactive oxygen species (ROS) and reactive nitrogen species (RNS) in seniors. Moreover, immune status in the elderly is weakened in part by immunosenescence, which is broadly defined as the decline in functionality of the immune system that corresponds with increasing age. The effects of immunosenescence on the expression of biomarkers potentially utilized in the clinical diagnosis of asthma remain unclear. It has also been shown that existing asthma treatments are less effective in the elderly. Thus, it is necessary that clinicians approach the diagnosis and treatment of asthmatic senior patients using innovative methods. Asthma in the elderly demands more intentional diagnostic and therapeutic research since it is potentially one of the few causes of mortality and morbidity in the elderly that is largely reversible. PMID- 26843629 TI - An In Vivo Pharmacological Screen Identifies Cholinergic Signaling as a Therapeutic Target in Glial-Based Nervous System Disease. AB - The role that glia play in neurological disease is poorly understood but increasingly acknowledged to be critical in a diverse group of disorders. Here we use a simple genetic model of Alexander disease, a progressive and severe human degenerative nervous system disease caused by a primary astroglial abnormality, to perform an in vivo screen of 1987 compounds, including many FDA-approved drugs and natural products. We identify four compounds capable of dose-dependent inhibition of nervous system toxicity. Focusing on one of these hits, glycopyrrolate, we confirm the role for muscarinic cholinergic signaling in pathogenesis using additional pharmacologic reagents and genetic approaches. We further demonstrate that muscarinic cholinergic signaling works through downstream Galphaq to control oxidative stress and death of neurons and glia. Importantly, we document increased muscarinic cholinergic receptor expression in Alexander disease model mice and in postmortem brain tissue from Alexander disease patients, and that blocking muscarinic receptors in Alexander disease model mice reduces oxidative stress, emphasizing the translational significance of our findings. We have therefore identified glial muscarinic signaling as a potential therapeutic target in Alexander disease, and possibly in other gliopathic disorders as well. SIGNIFICANCE STATEMENT: Despite the urgent need for better treatments for neurological diseases, drug development for these devastating disorders has been challenging. The effectiveness of traditional large-scale in vitro screens may be limited by the lack of the appropriate molecular, cellular, and structural environment. Using a simple Drosophila model of Alexander disease, we performed a moderate throughput chemical screen of FDA approved drugs and natural compounds, and found that reducing muscarinic cholinergic signaling ameliorated clinical symptoms and oxidative stress in Alexander disease model flies and mice. Our work demonstrates that small animal models are valuable screening tools for therapeutic compound identification in complex human diseases and that existing drugs can be a valuable resource for drug discovery given their known pharmacological and safety profiles. PMID- 26843630 TI - A New Mechanism of Receptor Targeting by Interaction between Two Classes of Ligand-Gated Ion Channels. AB - The 5-HT3 receptors are serotonin-gated ion channels that physically couple with purinergic P2X2 receptors to trigger a functional cross-inhibition leading to reciprocal channel occlusion. Although this functional receptor-receptor coupling seems to serve a modulatory role on both channels, this might not be its main physiological purpose. Using primary cultures of rat hippocampal neurons as a quantitative model of polarized targeting, we show here a novel function for this interaction. In this model, 5-HT3A receptors did not exhibit by themselves the capability of distal targeting in dendrites and axons but required the presence of P2X2R for their proper subcellular localization. 5-HT3AR distal targeting occurred with a delayed time course and exhibited a neuron phenotype dependency. In the subpopulation of neurons expressing endogenous P2X2R, 5-HT3AR distal neuritic localization correlated with P2X2R expression and could be selectively inhibited by P2X2R RNA interference. Cotransfection of both receptors revealed a specific colocalization, cotrafficking in common surface clusters, and the axonal rerouting of 5-HT3AR. The physical association between the two receptors was dependent on the second intracellular loop of the 5-HT3A subunit, but not on the P2X2R C-terminal tail that triggers the functional cross-inhibition with the 5 HT3AR. Together, these data establish that 5-HT3AR distal targeting in axons and dendrites primarily depends on P2X2R expression. Because several P2XR have now been shown to functionally interact with several other members of the 4-TMD family of receptor channels, we propose to reconsider the real functional role for this receptor family, as trafficking partner proteins dynamically involved in other receptors targeting. SIGNIFICANCE STATEMENT: So far, receptor targeting mechanisms were found to involve intracellular partner proteins or supramolecular complexes that couple receptors to cytoskeletal elements and recruit them into cargo vesicles. In this paper, we describe a new trafficking mechanism for the neuronal serotonin 5-HT3A ionotropic channel receptor, in which the role of routing partner is endowed by a functionally interacting purinergic receptor: the P2X2 receptor. This work not only unveils the mechanism by which 5-HT3 receptors can reach their axonal localization required for the control of neurotransmitter release, but also suggests that, in addition to their modulatory role, the family of P2X receptors could have a previously undescribed functional role of trafficking partner proteins dynamically involved in the targeting of other receptors. PMID- 26843631 TI - Human Visual Cortex Responses to Rapid Cone and Melanopsin-Directed Flicker. AB - Signals from cones are recombined in postreceptoral channels [luminance, L + M; red-green, L - M; blue-yellow, S - (L + M)]. The melanopsin-containing retinal ganglion cells are also active at daytime light levels and recent psychophysical results suggest that melanopsin contributes to conscious vision in humans. Here, we measured BOLD fMRI responses to spectral modulations that separately targeted the postreceptoral cone channels and melanopsin. Responses to spatially uniform (27.5 degrees field size, central 5 degrees obscured) flicker at 0.5, 1, 2, 4, 8, 16, 32, and 64 Hz were recorded from areas V1, V2/V3, motion-sensitive area MT, and the lateral occipital complex. In V1 and V2/V3, higher temporal sensitivity was observed to L + M + S (16 Hz) compared with L - M flicker (8 Hz), consistent with psychophysical findings. Area MT was most sensitive to rapid (32 Hz) flicker of either L + M + S or L - M. We found S cone responses only in areas V1 and V2/V3 (peak frequency: 4-8 Hz). In addition, we studied an L + M modulation and found responses that were effectively identical at all temporal frequencies to those recorded for the L + M + S modulation. Finally, we measured the cortical response to melanopsin-directed flicker and compared this response with control modulations that addressed stimulus imprecision and the possibility of stimulation of cones in the shadow of retinal blood vessels (penumbral cones). For our stimulus conditions, melanopsin flicker did not elicit a cortical response exceeding that of the control modulations. We note that failure to control for penumbral cone stimulation could be mistaken for a melanopsin response. SIGNIFICANCE STATEMENT: The retina contains cone photoreceptors and ganglion cells that contain the photopigment melanopsin. Cones provide brightness and color signals to visual cortex. Melanopsin influences circadian rhythm and the pupil, but its contribution to cortex and perception is less clear. We measured the response of human visual cortex with fMRI using spectral modulations tailored to stimulate the cones and melanopsin separately. We found that cortical responses to cone signals vary systematically across visual areas. Differences in temporal sensitivity for achromatic, red-green, and blue-yellow stimuli generally reflect the known perceptual properties of vision. We found that melanopsin signals do not produce a measurable response in visual cortex at temporal frequencies between 0.5 and 64 Hz at daytime light levels. PMID- 26843632 TI - Estradiol-Mediated Spine Changes in the Dorsal Hippocampus and Medial Prefrontal Cortex of Ovariectomized Female Mice Depend on ERK and mTOR Activation in the Dorsal Hippocampus. AB - Dendritic spine plasticity underlies the formation and maintenance of memories. Both natural fluctuations and systemic administration of 17beta-estradiol (E2) alter spine density in the dorsal hippocampus (DH) of rodents. DH E2 infusion enhances hippocampal-dependent memory by rapidly activating extracellular signal regulated kinase (ERK)-dependent signaling of mammalian target of rapamycin (mTOR), a key protein synthesis pathway involved in spine remodeling. Here, we investigated whether infusion of E2 directly into the DH drives spine changes in the DH and other brain regions, and identified cell-signaling pathways that mediate these effects. E2 significantly increased basal and apical spine density on CA1 pyramidal neurons 30 min and 2 h after infusion. DH E2 infusion also significantly increased basal spine density on pyramidal neurons in the medial prefrontal cortex (mPFC) 2 h later, suggesting that E2-mediated activity in the DH drives mPFC spinogenesis. The increase in CA1 and mPFC spine density observed 2 h after intracerebroventricular infusion of E2 was blocked by DH infusion of an ERK or mTOR inhibitor. DH E2 infusion did not affect spine density in the dentate gyrus or ventromedial hypothalamus, suggesting specific effects of E2 on the DH and mPFC. Collectively, these data demonstrate that DH E2 treatment elicits ERK- and mTOR-dependent spinogenesis on CA1 and mPFC pyramidal neurons, effects that may support the memory-enhancing effects of E2. SIGNIFICANCE STATEMENT: Although systemically injected 17beta-estradiol (E2) increases CA1 dendritic spine density, the molecular mechanisms regulating E2-induced spinogenesis in vivo are largely unknown. We found that E2 infused directly into the dorsal hippocampus (DH) increased CA1 spine density 30 min and 2 h later. Surprisingly, DH E2 infusion also increased spine density in the medial prefrontal cortex (mPFC), suggesting that estrogenic regulation of the DH influences mPFC spinogenesis. Moreover, inhibition of ERK and mTOR activation in the DH prevented E2 from increasing DH and mPFC spines, demonstrating that DH ERK and mTOR activation is necessary for E2-induced spinogenesis in the DH and mPFC. These findings provide novel insights into the molecular mechanisms through which E2 mediates dendritic spine density in CA1 and mPFC. PMID- 26843633 TI - The Semantic Network at Work and Rest: Differential Connectivity of Anterior Temporal Lobe Subregions. AB - The anterior temporal lobe (ATL) makes a critical contribution to semantic cognition. However, the functional connectivity of the ATL and the functional network underlying semantic cognition has not been elucidated. In addition, subregions of the ATL have distinct functional properties and thus the potential differential connectivity between these subregions requires investigation. We explored these aims using both resting-state and active semantic task data in humans in combination with a dual-echo gradient echo planar imaging (EPI) paradigm designed to ensure signal throughout the ATL. In the resting-state analysis, the ventral ATL (vATL) and anterior middle temporal gyrus (MTG) were shown to connect to areas responsible for multimodal semantic cognition, including bilateral ATL, inferior frontal gyrus, medial prefrontal cortex, angular gyrus, posterior MTG, and medial temporal lobes. In contrast, the anterior superior temporal gyrus (STG)/superior temporal sulcus was connected to a distinct set of auditory and language-related areas, including bilateral STG, precentral and postcentral gyri, supplementary motor area, supramarginal gyrus, posterior temporal cortex, and inferior and middle frontal gyri. Complementary analyses of functional connectivity during an active semantic task were performed using a psychophysiological interaction (PPI) analysis. The PPI analysis highlighted the same semantic regions suggesting a core semantic network active during rest and task states. This supports the necessity for semantic cognition in internal processes occurring during rest. The PPI analysis showed additional connectivity of the vATL to regions of occipital and frontal cortex. These areas strongly overlap with regions found to be sensitive to executively demanding, controlled semantic processing. SIGNIFICANCE STATEMENT: Previous studies have shown that semantic cognition depends on subregions of the anterior temporal lobe (ATL). However, the network of regions functionally connected to these subregions has not been demarcated. Here, we show that these ventrolateral anterior temporal subregions form part of a network responsible for semantic processing during both rest and an explicit semantic task. This demonstrates the existence of a core functional network responsible for multimodal semantic cognition regardless of state. Distinct connectivity is identified in the superior ATL, which is connected to auditory and language areas. Understanding the functional connectivity of semantic cognition allows greater understanding of how this complex process may be performed and the role of distinct subregions of the anterior temporal cortex. PMID- 26843634 TI - Blockade of Astrocytic Calcineurin/NFAT Signaling Helps to Normalize Hippocampal Synaptic Function and Plasticity in a Rat Model of Traumatic Brain Injury. AB - Increasing evidence suggests that the calcineurin (CN)-dependent transcription factor NFAT (Nuclear Factor of Activated T cells) mediates deleterious effects of astrocytes in progressive neurodegenerative conditions. However, the impact of astrocytic CN/NFAT signaling on neural function/recovery after acute injury has not been investigated extensively. Using a controlled cortical impact (CCI) procedure in rats, we show that traumatic brain injury is associated with an increase in the activities of NFATs 1 and 4 in the hippocampus at 7 d after injury. NFAT4, but not NFAT1, exhibited extensive labeling in astrocytes and was found throughout the axon/dendrite layers of CA1 and the dentate gyrus. Blockade of the astrocytic CN/NFAT pathway in rats using adeno-associated virus (AAV) vectors expressing the astrocyte-specific promoter Gfa2 and the NFAT-inhibitory peptide VIVIT prevented the injury-related loss of basal CA1 synaptic strength and key synaptic proteins and reduced the susceptibility to induction of long term depression. In conjunction with these seemingly beneficial effects, VIVIT treatment elicited a marked increase in the expression of the prosynaptogenic factor SPARCL1 (hevin), especially in hippocampal tissue ipsilateral to the CCI injury. However, in contrast to previous work on Alzheimer's mouse models, AAV Gfa2-VIVIT had no effects on the levels of GFAP and Iba1, suggesting that synaptic benefits of VIVIT were not attributable to a reduction in glial activation per se. Together, the results implicate the astrocytic CN/NFAT4 pathway as a key mechanism for disrupting synaptic remodeling and homeostasis in the hippocampus after acute injury. SIGNIFICANCE STATEMENT: Similar to microglia, astrocytes become strongly "activated" with neural damage and exhibit numerous morphologic/biochemical changes, including an increase in the expression/activity of the protein phosphatase calcineurin. Using adeno-associated virus (AAV) to inhibit the calcineurin-dependent activation of the transcription factor NFAT (Nuclear Factor of Activated T cells) selectively, we have shown that activated astrocytes contribute to neural dysfunction in animal models characterized by progressive/chronic neuropathology. Here, we show that the suppression of astrocytic calcineurin/NFATs helps to protect synaptic function and plasticity in an animal model in which pathology arises from a single traumatic brain injury. The findings suggest that at least some astrocyte functions impair recovery after trauma and may provide druggable targets for treating victims of acute nervous system injury. PMID- 26843635 TI - Post-Movement Beta Activity in Sensorimotor Cortex Indexes Confidence in the Estimations from Internal Models. AB - Beta oscillations are a dominant feature of the sensorimotor system. A transient and prominent increase in beta oscillations is consistently observed across the sensorimotor cortical-basal ganglia network after cessation of voluntary movement: the post-movement beta synchronization (PMBS). Current theories about the function of the PMBS have been focused on either the closure of motor response or the processing of sensory afferance. Computational models of sensorimotor control have emphasized the importance of the integration between feedforward estimation and sensory feedback, and therefore the putative motor and sensory functions of beta oscillations may reciprocally interact with each other and in fact be indissociable. Here we show that the amplitude of sensorimotor PMBS is modulated by the history of visual feedback of task-relevant errors, and negatively correlated with the trial-to-trial exploratory adjustment in a sensorimotor adaptation task in young healthy human subjects. The PMBS also negatively correlated with the uncertainty associated with the feedforward estimation, which was recursively updated in light of new sensory feedback, as identified by a Bayesian learning model. These results reconcile the two opposing motor and sensory views of the function of PMBS, and suggest a unifying theory in which PMBS indexes the confidence in internal feedforward estimation in Bayesian sensorimotor integration. Its amplitude simultaneously reflects cortical sensory processing and signals the need for maintenance or adaptation of the motor output, and if necessary, exploration to identify an altered sensorimotor transformation. SIGNIFICANCE STATEMENT: For optimal sensorimotor control, sensory feedback and feedforward estimation of a movement's sensory consequences should be weighted by the inverse of their corresponding uncertainties, which require recursive updating in a dynamic environment. We show that post-movement beta activity (13-30 Hz) over sensorimotor cortex in young healthy subjects indexes the evaluation of uncertainty in feedforward estimation. Our work contributes to the understanding of the function of beta oscillations in sensorimotor control, and provides further insight into how aberrant beta activity can contribute to the pathophysiology of movement disorders. PMID- 26843636 TI - Goal-Directed Decision Making with Spiking Neurons. AB - Behavioral and neuroscientific data on reward-based decision making point to a fundamental distinction between habitual and goal-directed action selection. The formation of habits, which requires simple updating of cached values, has been studied in great detail, and the reward prediction error theory of dopamine function has enjoyed prominent success in accounting for its neural bases. In contrast, the neural circuit mechanisms of goal-directed decision making, requiring extended iterative computations to estimate values online, are still unknown. Here we present a spiking neural network that provably solves the difficult online value estimation problem underlying goal-directed decision making in a near-optimal way and reproduces behavioral as well as neurophysiological experimental data on tasks ranging from simple binary choice to sequential decision making. Our model uses local plasticity rules to learn the synaptic weights of a simple neural network to achieve optimal performance and solves one-step decision-making tasks, commonly considered in neuroeconomics, as well as more challenging sequential decision-making tasks within 1 s. These decision times, and their parametric dependence on task parameters, as well as the final choice probabilities match behavioral data, whereas the evolution of neural activities in the network closely mimics neural responses recorded in frontal cortices during the execution of such tasks. Our theory provides a principled framework to understand the neural underpinning of goal-directed decision making and makes novel predictions for sequential decision-making tasks with multiple rewards. SIGNIFICANCE STATEMENT: Goal-directed actions requiring prospective planning pervade decision making, but their circuit-level mechanisms remain elusive. We show how a model circuit of biologically realistic spiking neurons can solve this computationally challenging problem in a novel way. The synaptic weights of our network can be learned using local plasticity rules such that its dynamics devise a near-optimal plan of action. By systematically comparing our model results to experimental data, we show that it reproduces behavioral decision times and choice probabilities as well as neural responses in a rich set of tasks. Our results thus offer the first biologically realistic account for complex goal-directed decision making at a computational, algorithmic, and implementational level. PMID- 26843638 TI - Cyfip1 Regulates Presynaptic Activity during Development. AB - Copy number variations encompassing the gene encoding Cyfip1 have been associated with a variety of human diseases, including autism and schizophrenia. Here we show that juvenile mice hemizygous for Cyfip1 have altered presynaptic function, enhanced protein translation, and increased levels of F-actin. In developing hippocampus, reduced Cyfip1 levels serve to decrease paired pulse facilitation and increase miniature EPSC frequency without a change in amplitude. Higher resolution examination shows these changes to be caused primarily by an increase in presynaptic terminal size and enhanced vesicle release probability. Short hairpin-mediated knockdown of Cyfip1 coupled with expression of mutant Cyfip1 proteins indicates that the presynaptic alterations are caused by dysregulation of the WAVE regulatory complex. Such dysregulation occurs downstream of Rac1 as acute exposure to Rac1 inhibitors rescues presynaptic responses in culture and in hippocampal slices. The data serve to highlight an early and essential role for Cyfip1 in the generation of normally functioning synapses and suggest a means by which changes in Cyfip1 levels could impact the generation of neural networks and contribute to abnormal and maladaptive behaviors. SIGNIFICANCE STATEMENT: Several developmental brain disorders have been associated with gene duplications and deletions that serve to increase or decrease levels of encoded proteins. Cyfip1 is one such protein, but the role it plays in brain development is poorly understood. We asked whether decreased Cyfip1 levels altered the function of developing synapses. The data show that synapses with reduced Cyfip1 are larger and release neurotransmitter more rapidly. These effects are due to Cyfip1's role in actin polymerization and are reversed by expression of a Cyfip1 mutant protein retaining actin regulatory function or by inhibiting Rac1. Thus, Cyfip1 has a more prominent early role regulating presynaptic activity during a stage of development when activity helps to define neural pathways. PMID- 26843637 TI - Nonspatial Sequence Coding in CA1 Neurons. AB - The hippocampus is critical to the memory for sequences of events, a defining feature of episodic memory. However, the fundamental neuronal mechanisms underlying this capacity remain elusive. While considerable research indicates hippocampal neurons can represent sequences of locations, direct evidence of coding for the memory of sequential relationships among nonspatial events remains lacking. To address this important issue, we recorded neural activity in CA1 as rats performed a hippocampus-dependent sequence-memory task. Briefly, the task involves the presentation of repeated sequences of odors at a single port and requires rats to identify each item as "in sequence" or "out of sequence". We report that, while the animals' location and behavior remained constant, hippocampal activity differed depending on the temporal context of items-in this case, whether they were presented in or out of sequence. Some neurons showed this effect across items or sequence positions (general sequence cells), while others exhibited selectivity for specific conjunctions of item and sequence position information (conjunctive sequence cells) or for specific probe types (probe specific sequence cells). We also found that the temporal context of individual trials could be accurately decoded from the activity of neuronal ensembles, that sequence coding at the single-cell and ensemble level was linked to sequence memory performance, and that slow-gamma oscillations (20-40 Hz) were more strongly modulated by temporal context and performance than theta oscillations (4 12 Hz). These findings provide compelling evidence that sequence coding extends beyond the domain of spatial trajectories and is thus a fundamental function of the hippocampus. SIGNIFICANCE STATEMENT: The ability to remember the order of life events depends on the hippocampus, but the underlying neural mechanisms remain poorly understood. Here we addressed this issue by recording neural activity in hippocampal region CA1 while rats performed a nonspatial sequence memory task. We found that hippocampal neurons code for the temporal context of items (whether odors were presented in the correct or incorrect sequential position) and that this activity is linked with memory performance. The discovery of this novel form of temporal coding in hippocampal neurons advances our fundamental understanding of the neurobiology of episodic memory and will serve as a foundation for our cross-species, multitechnique approach aimed at elucidating the neural mechanisms underlying memory impairments in aging and dementia. PMID- 26843639 TI - Imaging Dopamine and Serotonin Systems on MPTP Monkeys: A Longitudinal PET Investigation of Compensatory Mechanisms. AB - It is now widely accepted that compensatory mechanisms are involved during the early phase of Parkinson's disease (PD) to delay the expression of motor symptoms. However, the neurochemical mechanisms underlying this presymptomatic period are still unclear. Here, we measured in vivo longitudinal changes of both the dopaminergic and serotonergic systems in seven asymptomatic 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-intoxicated monkeys (when motor symptoms are less apparent) using PET. We used the progressively MPTP-intoxicated monkey model that expresses recovery from motor symptoms to study the changes in dopamine synthesis ([(18)F]DOPA), dopamine D2/D3 receptors ([(11)C]raclopride), and serotonin transporter (11)C-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio) benzylamine ([(11)C]DASB) and serotonin 1A receptor ([(18)F]MPPF) levels between four different states (baseline, early symptomatic, full symptomatic and recovered). During the early symptomatic state, we observed increases of [(18)F]DOPA uptake in the anterior putamen, [(11)C]raclopride binding in the posterior striatum, and 2'-methoxyphenyl-(N-2'-pyridinyl)-p-[(18)F]fluoro benzamidoethylpiperazine [(18)F]MPPF uptake in the orbitofrontal cortex and dorsal ACC. After recovery from motor symptoms, the results mainly showed decreased [(11)C]raclopride binding in the anterior striatum and limbic ACC. In addition, our findings supported the importance of pallidal dopaminergic neurotransmission in both the early compensatory mechanisms and the functional recovery mechanisms, with reduced aromatic L-amino acid decarboxylase (AAAD) activity closely related to the appearance or perseveration of motor symptoms. In parallel, this study provides preliminary evidence of the role of the serotonergic system in compensatory mechanisms. Nonetheless, future studies are needed to determine whether there are changes in SERT availability in the early symptomatic state and if [(18)F]MPPF PET imaging might be a promising biomarker of early degenerative changes in PD. SIGNIFICANCE STATEMENT: The present research provides evidence of the potential of combining a multitracer PET imaging technique and a longitudinal protocol applied on a progressively 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine-intoxicated monkey model to further elucidate the nature of the compensatory mechanisms involved in the preclinical period of Parkinson's disease (PD). In particular, by investigating the dopaminergic and serotonergic changes both presynaptically and postsynaptically at four different motor states (baseline, early symptomatic, full symptomatic, and recovered), this study has allowed us to identify putative biomarkers for future therapeutic interventions to prevent and/or delay disease expression. For example, our findings suggest that the external pallidum could be a new target for cell-based therapies to reduce PD symptoms. PMID- 26843640 TI - Abeta-Induced Synaptic Alterations Require the E3 Ubiquitin Ligase Nedd4-1. AB - Alzheimer's disease (AD) is a neurodegenerative disease in which patients experience progressive cognitive decline. A wealth of evidence suggests that this cognitive impairment results from synaptic dysfunction in affected brain regions caused by cleavage of amyloid precursor protein into the pathogenic peptide amyloid-beta (Abeta). Specifically, it has been shown that Abeta decreases surface AMPARs, dendritic spine density, and synaptic strength, and also alters synaptic plasticity. The precise molecular mechanisms by which this occurs remain unclear. Here we demonstrate a role for ubiquitination in Abeta-induced synaptic dysfunction in cultured rat neurons. We find that Abeta promotes the ubiquitination of AMPARs, as well as the redistribution and recruitment of Nedd4 1, a HECT E3 ubiquitin ligase we previously demonstrated to target AMPARs for ubiquitination and degradation. Strikingly, we show that Nedd4-1 is required for Abeta-induced reductions in surface AMPARs, synaptic strength, and dendritic spine density. Our findings, therefore, indicate an important role for Nedd4-1 and ubiquitin in the synaptic alterations induced by Abeta. SIGNIFICANCE STATEMENT: Synaptic changes in Alzheimer's disease (AD) include surface AMPAR loss, which can weaken synapses. In a cell culture model of AD, we found that AMPAR loss correlates with increased AMPAR ubiquitination. In addition, the ubiquitin ligase Nedd4-1, known to ubiquitinate AMPARs, is recruited to synapses in response to Abeta. Strikingly, reducing Nedd4-1 levels in this model prevented surface AMPAR loss and synaptic weakening. These findings suggest that, in AD, Nedd4-1 may ubiquitinate AMPARs to promote their internalization and weaken synaptic strength, similar to what occurs in Nedd4-1's established role in homeostatic synaptic scaling. This is the first demonstration of Abeta-mediated control of a ubiquitin ligase to regulate surface AMPAR expression. PMID- 26843641 TI - Left Superior Temporal Gyrus Is Coupled to Attended Speech in a Cocktail-Party Auditory Scene. AB - Using a continuous listening task, we evaluated the coupling between the listener's cortical activity and the temporal envelopes of different sounds in a multitalker auditory scene using magnetoencephalography and corticovocal coherence analysis. Neuromagnetic signals were recorded from 20 right-handed healthy adult humans who listened to five different recorded stories (attended speech streams), one without any multitalker background (No noise) and four mixed with a "cocktail party" multitalker background noise at four signal-to-noise ratios (5, 0, -5, and -10 dB) to produce speech-in-noise mixtures, here referred to as Global scene. Coherence analysis revealed that the modulations of the attended speech stream, presented without multitalker background, were coupled at ~0.5 Hz to the activity of both superior temporal gyri, whereas the modulations at 4-8 Hz were coupled to the activity of the right supratemporal auditory cortex. In cocktail party conditions, with the multitalker background noise, the coupling was at both frequencies stronger for the attended speech stream than for the unattended Multitalker background. The coupling strengths decreased as the Multitalker background increased. During the cocktail party conditions, the ~0.5 Hz coupling became left-hemisphere dominant, compared with bilateral coupling without the multitalker background, whereas the 4-8 Hz coupling remained right hemisphere lateralized in both conditions. The brain activity was not coupled to the multitalker background or to its individual talkers. The results highlight the key role of listener's left superior temporal gyri in extracting the slow ~0.5 Hz modulations, likely reflecting the attended speech stream within a multitalker auditory scene. SIGNIFICANCE STATEMENT: When people listen to one person in a "cocktail party," their auditory cortex mainly follows the attended speech stream rather than the entire auditory scene. However, how the brain extracts the attended speech stream from the whole auditory scene and how increasing background noise corrupts this process is still debated. In this magnetoencephalography study, subjects had to attend a speech stream with or without multitalker background noise. Results argue for frequency-dependent cortical tracking mechanisms for the attended speech stream. The left superior temporal gyrus tracked the ~0.5 Hz modulations of the attended speech stream only when the speech was embedded in multitalker background, whereas the right supratemporal auditory cortex tracked 4-8 Hz modulations during both noiseless and cocktail-party conditions. PMID- 26843643 TI - The Effect of Early Visual Deprivation on the Neural Bases of Auditory Processing. AB - Transient congenital visual deprivation affects visual and multisensory processing. In contrast, the extent to which it affects auditory processing has not been investigated systematically. Research in permanently blind individuals has revealed brain reorganization during auditory processing, involving both intramodal and crossmodal plasticity. The present study investigated the effect of transient congenital visual deprivation on the neural bases of auditory processing in humans. Cataract-reversal individuals and normally sighted controls performed a speech-in-noise task while undergoing functional magnetic resonance imaging. Although there were no behavioral group differences, groups differed in auditory cortical responses: in the normally sighted group, auditory cortex activation increased with increasing noise level, whereas in the cataract reversal group, no activation difference was observed across noise levels. An auditory activation of visual cortex was not observed at the group level in cataract-reversal individuals. The present data suggest prevailing auditory processing advantages after transient congenital visual deprivation, even many years after sight restoration. SIGNIFICANCE STATEMENT: The present study demonstrates that people whose sight was restored after a transient period of congenital blindness show more efficient cortical processing of auditory stimuli (here speech), similarly to what has been observed in congenitally permanently blind individuals. These results underscore the importance of early sensory experience in permanently shaping brain function. PMID- 26843642 TI - Behaviorally Relevant Abstract Object Identity Representation in the Human Parietal Cortex. AB - The representation of object identity is fundamental to human vision. Using fMRI and multivoxel pattern analysis, here we report the representation of highly abstract object identity information in human parietal cortex. Specifically, in superior intraparietal sulcus (IPS), a region previously shown to track visual short-term memory capacity, we found object identity representations for famous faces varying freely in viewpoint, hairstyle, facial expression, and age; and for well known cars embedded in different scenes, and shown from different viewpoints and sizes. Critically, these parietal identity representations were behaviorally relevant as they closely tracked the perceived face-identity similarity obtained in a behavioral task. Meanwhile, the task-activated regions in prefrontal and parietal cortices (excluding superior IPS) did not exhibit such abstract object identity representations. Unlike previous studies, we also failed to observe identity representations in posterior ventral and lateral visual object processing regions, likely due to the greater amount of identity abstraction demanded by our stimulus manipulation here. Our MRI slice coverage precluded us from examining identity representation in anterior temporal lobe, a likely region for the computing of identity information in the ventral region. Overall, we show that human parietal cortex, part of the dorsal visual processing pathway, is capable of holding abstract and complex visual representations that are behaviorally relevant. These results argue against a "content-poor" view of the role of parietal cortex in attention. Instead, the human parietal cortex seems to be "content rich" and capable of directly participating in goal-driven visual information representation in the brain. SIGNIFICANCE STATEMENT: The representation of object identity (including faces) is fundamental to human vision and shapes how we interact with the world. Although object representation has traditionally been associated with human occipital and temporal cortices, here we show, by measuring fMRI response patterns, that a region in the human parietal cortex can robustly represent task-relevant object identities. These representations are invariant to changes in a host of visual features, such as viewpoint, and reflect an abstract level of representation that has not previously been reported in the human parietal cortex. Critically, these neural representations are behaviorally relevant as they closely track the perceived object identities. Human parietal cortex thus participates in the moment-to moment goal-directed visual information representation in the brain. PMID- 26843644 TI - Oncomodulin, an EF-Hand Ca2+ Buffer, Is Critical for Maintaining Cochlear Function in Mice. AB - Oncomodulin (Ocm), a member of the parvalbumin family of calcium binding proteins, is expressed predominantly by cochlear outer hair cells in subcellular regions associated with either mechanoelectric transduction or electromotility. Targeted deletion of Ocm caused progressive cochlear dysfunction. Although sound evoked responses are normal at 1 month, by 4 months, mutants show only minimal distortion product otoacoustic emissions and 70-80 dB threshold shifts in auditory brainstem responses. Thus, Ocm is not critical for cochlear development but does play an essential role for cochlear function in the adult mouse. SIGNIFICANCE STATEMENT: Numerous proteins act as buffers, sensors, or pumps to control calcium levels in cochlear hair cells. In the inner ear, EF-hand calcium buffers may play a significant role in hair cell function but have been very difficult to study. Unlike other reports of genetic disruption of EF-hand calcium buffers, deletion of oncomodulin (Ocm), which is predominately found in outer hair cells, leads to a progressive hearing loss after 1 month, suggesting that Ocm critically protects hearing in the mature ear. PMID- 26843645 TI - Chronic Ampakine Treatments Stimulate Dendritic Growth and Promote Learning in Middle-Aged Rats. AB - Positive allosteric modulators of AMPA-type glutamate receptors (ampakines) have been shown to rescue synaptic plasticity and reduce neuropathology in rodent models of cognitive disorders. Here we tested whether chronic ampakine treatment offsets age-related dendritic retraction in middle-aged (MA) rats. Starting at 10 months of age, rats were housed in an enriched environment and given daily treatment with a short half-life ampakine or vehicle for 3 months. Dendritic branching and spine measures were collected from 3D reconstructions of Lucifer yellow-filled CA1 pyramidal cells. There was a substantial loss of secondary branches, relative to enriched 2.5-month-old rats, in apical and basal dendritic fields of vehicle-treated, but not ampakine-treated, 13-month-old rats. Baseline synaptic responses in CA1 were only subtly different between the two MA groups, but long-term potentiation was greater in ampakine-treated rats. Unsupervised learning of a complex environment was used to assess treatment effects on behavior. Vehicle- and drug-treated rats behaved similarly during a first 30 min session in the novel environment but differed markedly on subsequent measures of long-term memory. Markov sequence analysis uncovered a clear increase in the predictability of serial movements between behavioral sessions 2 and 3 in the ampakine, but not vehicle, group. These results show that a surprising degree of dendritic retraction occurs by middle age and that this can be mostly offset by pharmacological treatments without evidence for unwanted side effects. The functional consequences of rescue were prominent with regard to memory but also extended to self-organization of behavior. SIGNIFICANCE STATEMENT: Brain aging is characterized by a progressive loss of dendritic arbors and the emergence of impairments to learning-related synaptic plasticity. The present studies show that dendritic losses are evident by middle age despite housing in an enriched environment and can be mostly reversed by long-term, oral administration of a positive allosteric modulator of AMPA-type glutamate receptors. Dendritic recovery was accompanied by improvements to both synaptic plasticity and the encoding of long-term memory of a novel, complex environment. Because the short half-life compound had no evident negative effects, the results suggest a plausible strategy for treating age-related neuronal deterioration. PMID- 26843646 TI - Higher-Order Sensory Cortex Drives Basolateral Amygdala Activity during the Recall of Remote, but Not Recently Learned Fearful Memories. AB - Negative experiences are quickly learned and long remembered. Key unresolved issues in the field of emotional memory include identifying the loci and dynamics of memory storage and retrieval. The present study examined neural activity in the higher-order auditory cortex Te2 and basolateral amygdala (BLA) and their crosstalk during the recall of recent and remote fear memories. To this end, we obtained local field potentials and multiunit activity recordings in Te2 and BLA of rats that underwent recall at 24 h and 30 d after the association of an acoustic conditioned (CS, tone) and an aversive unconditioned stimulus (US, electric shock). Here we show that, during the recall of remote auditory threat memories in rats, the activity of the Te2 and BLA is highly synchronized in the theta frequency range. This functional connectivity stems from memory consolidation processes because it is present during remote, but not recent, memory retrieval. Moreover, the observed increase in synchrony is cue and region specific. A preponderant Te2-to-BLA directionality characterizes this dialogue, and the percentage of time Te2 theta leads the BLA during remote memory recall correlates with a faster latency to freeze to the auditory conditioned stimulus. The blockade of this information transfer via Te2 inhibition with muscimol prevents any retrieval-evoked neuronal activity in the BLA and animals are unable to retrieve remote memories. We conclude that memories stored in higher-order sensory cortices drive BLA activity when distinguishing between learned threatening and neutral stimuli. SIGNIFICANCE STATEMENT: How and where in the brain do we store the affective/motivational significance of sensory stimuli acquired through life experiences? Scientists have long investigated how "limbic" structures, such as the amygdala, process affective stimuli. Here we show that retrieval of well-established threat memories requires the functional interplay between higher-order components of the auditory cortex and the amygdala via synchrony in the theta range. This functional connectivity is a result of memory consolidation processes and is characterized by a predominant cortical to amygdala direction of information transfer. This connectivity is predictive of the animals' ability to recognize auditory stimuli as aversive. In the absence of this necessary cortical activity, the amygdala is unable to distinguish between frightening and neutral stimuli. PMID- 26843647 TI - Persistent Electrical Activity in Primary Nociceptors after Spinal Cord Injury Is Maintained by Scaffolded Adenylyl Cyclase and Protein Kinase A and Is Associated with Altered Adenylyl Cyclase Regulation. AB - Little is known about intracellular signaling mechanisms that persistently excite neurons in pain pathways. Persistent spontaneous activity (SA) generated in the cell bodies of primary nociceptors within dorsal root ganglia (DRG) has been found to make major contributions to chronic pain in a rat model of spinal cord injury (SCI) (Bedi et al., 2010; Yang et al., 2014). The occurrence of SCI induced SA in a large fraction of DRG neurons and the persistence of this SA long after dissociation of the neurons provide an opportunity to define intrinsic cell signaling mechanisms that chronically drive SA in pain pathways. The present study demonstrates that SCI-induced SA requires continuing activity of adenylyl cyclase (AC) and cAMP-dependent protein kinase (PKA), as well as a scaffolded complex containing AC5/6, A-kinase anchoring protein 150 (AKAP150), and PKA. SCI caused a small but significant increase in the expression of AKAP150 but not other AKAPs. DRG membranes isolated from SCI animals revealed a novel alteration in the regulation of AC. AC activity stimulated by Ca(2+)-calmodulin increased, while the inhibition of AC activity by Galphai showed an unexpected and dramatic decrease after SCI. Localized enhancement of the activity of AC within scaffolded complexes containing PKA is likely to contribute to chronic pathophysiological consequences of SCI, including pain, that are promoted by persistent hyperactivity in DRG neurons. SIGNIFICANCE STATEMENT: Chronic neuropathic pain is a major clinical problem with poorly understood mechanisms and inadequate treatments. Recent findings indicate that chronic pain in a rat SCI model depends upon hyperactivity in dorsal root ganglia (DRG) neurons. Although cAMP signaling is involved in many forms of neural plasticity, including hypersensitivity of nociceptors in the presence of inflammatory mediators, our finding that continuing cAMP-PKA signaling is required for persistent SA months after SCI and long after isolation of nociceptors is surprising. The dependence of ongoing SA upon AKAP150 and AC5/6 was unknown. The discovery of a dramatic decrease in Galphai inhibition of AC activity after SCI is novel for any physiological system and potentially has broad implications for understanding chronic pain mechanisms. PMID- 26843648 TI - Sex Differences in GABAA Signaling in the Periaqueductal Gray Induced by Persistent Inflammation. AB - The ventrolateral periaqueductal gray (vlPAG) is a key structure in the descending pain modulatory circuit. Activation of the circuit occurs via disinhibition of GABAergic inputs onto vlPAG output neurons. In these studies, we tested the hypothesis that GABAergic inhibition is increased during persistent inflammation, dampening activation of the descending circuit from the vlPAG. Our results indicate that persistent inflammation induced by Complete Freund's adjuvant (CFA) modulates GABA signaling differently in male and female rats. CFA treatment results in increased presynaptic GABA release but decreased high affinity tonic GABAA currents in female vlPAG neurons. These effects are not observed in males. The tonic currents in the vlPAG are dependent on GABA transporter activity and are modulated by agonists that activate GABAA receptors containing the delta subunit. The GABAA delta agonist THIP (gaboxadol) induced similar amplitude currents in naive and CFA-treated rats. In addition, a positive allosteric modulator of the GABAA delta subunit, DS2 (4-chloro-N-[2-(2 thienyl)imidazo[1,2-a]pyridin-3-yl]benzamide), increased tonic currents. These results indicate that GABAA delta receptors remain on the cell surface but are less active in CFA-treated female rats. In vivo behavior studies showed that morphine induced greater antinociception in CFA-treated females that was reversed with microinjections of DS2 directly into the vlPAG. DS2 did not affect morphine antinociception in naive or CFA-treated male rats. Together, these data indicate that sex-specific adaptations in GABAA receptor signaling modulate opioid analgesia in persistent inflammation. Antagonists of GABAA delta receptors may be a viable strategy for reducing pain associated with persistent inflammation, particularly in females. SIGNIFICANCE STATEMENT: These studies demonstrate that GABA signaling is modulated in the ventrolateral periaqueductal gray by persistent inflammation differently in female and male rats. Our results indicate that antagonists or negative allosteric modulators of GABAA delta receptors may be an effective strategy to alleviate chronic inflammatory pain and promote opioid antinociception, especially in females. PMID- 26843649 TI - Color-Biased Regions of the Ventral Visual Pathway Lie between Face- and Place Selective Regions in Humans, as in Macaques. AB - The existence of color-processing regions in the human ventral visual pathway (VVP) has long been known from patient and imaging studies, but their location in the cortex relative to other regions, their selectivity for color compared with other properties (shape and object category), and their relationship to color processing regions found in nonhuman primates remain unclear. We addressed these questions by scanning 13 subjects with fMRI while they viewed two versions of movie clips (colored, achromatic) of five different object classes (faces, scenes, bodies, objects, scrambled objects). We identified regions in each subject that were selective for color, faces, places, and object shape, and measured responses within these regions to the 10 conditions in independently acquired data. We report two key findings. First, the three previously reported color-biased regions (located within a band running posterior-anterior along the VVP, present in most of our subjects) were sandwiched between face-selective cortex and place-selective cortex, forming parallel bands of face, color, and place selectivity that tracked the fusiform gyrus/collateral sulcus. Second, the posterior color-biased regions showed little or no selectivity for object shape or for particular stimulus categories and showed no interaction of color preference with stimulus category, suggesting that they code color independently of shape or stimulus category; moreover, the shape-biased lateral occipital region showed no significant color bias. These observations mirror results in macaque inferior temporal cortex (Lafer-Sousa and Conway, 2013), and taken together, these results suggest a homology in which the entire tripartite face/color/place system of primates migrated onto the ventral surface in humans over the course of evolution. SIGNIFICANCE STATEMENT: Here we report that color biased cortex is sandwiched between face-selective and place-selective cortex on the bottom surface of the brain in humans. This face/color/place organization mirrors that seen on the lateral surface of the temporal lobe in macaques, suggesting that the entire tripartite system is homologous between species. This result validates the use of macaques as a model for human vision, making possible more powerful investigations into the connectivity, precise neural codes, and development of this part of the brain. In addition, we find substantial segregation of color from shape selectivity in posterior regions, as observed in macaques, indicating a considerable dissociation of the processing of shape and color in both species. PMID- 26843651 TI - Principles Governing DNA Methylation during Neuronal Lineage and Subtype Specification. AB - Although comprehensively described during early neuronal development, the role of DNA methylation/demethylation in neuronal lineage and subtype specification is not well understood. By studying two distinct neuronal progenitors as they differentiate to principal neurons in mouse hippocampus and striatum, we uncovered several principles governing neuronal DNA methylation during brain development. (1) The program consists of three stages: an initial genome-wide methylation during progenitor proliferation is followed by loss of methylation during the transition of regional progenitors to "young" hippocampal/striatal neurons, which is then reversed by gain in methylation during maturation to subtype-specific neurons. (2) At the first two stages, gain and loss of methylation are limited to CpGs, whereas during the third maturation stage, methylation also occurs at non-CpG sites in both lineages. (3) Methylation/demethylation, similar to transcription, are initially highly similar in the two lineages, whereas diversification in methylation and transcription during maturation creates subtype-specific methylation differences. (4) Initially, methylation targets all genomic locations, whereas later, during early and late differentiation, the preferred targets are intronic/intergenic sequences with enhancer-like activity. (5) Differentially methylated genes are enriched in sequential neurodevelopmental functions (such as progenitor proliferation, migration, neuritogenesis, and synaptic transmission); upregulated genes represent current and consecutive stage-specific functions, and downregulated genes represent preceding functions that are no longer required. The main conclusion of our work is that the neuronal methylation/demethylation program is predominantly developmental with minimal lineage specificity, except in the final stage of development when neuron subtype-specific differences also emerge. SIGNIFICANCE STATEMENT: Our work is the first to describe a set of relatively simple rules that govern DNA methylation and demethylation in neuronal development in vivo. By dividing neurodevelopment to three major stages and applying rules to each of them, we created a matrix that comprehensively describes DNA methylation/demethylation events in two neuronal lineages, with a total of 10 cell types spanning the entire neurodevelopment. Beyond increasing our understanding of the epigenetic regulation of normal development, our work will be useful in deciphering how environmental perturbations, such as gestational toxins, drugs, stress, infection, and offspring neglect/maltreatment, interfere with the developmental methylation program. PMID- 26843650 TI - Remyelinating Oligodendrocyte Precursor Cell miRNAs from the Sfmbt2 Cluster Promote Cell Cycle Arrest and Differentiation. AB - Oligodendrocyte (OL) loss contributes to the functional deficits underlying diseases with a demyelinating component. Remyelination by oligodendrocyte progenitor cells (OPCs) can restore these deficits. To understand the role that microRNAs (miRNAs) play in remyelination, 2',3'-cyclic-nucleotide 3' phosphodiesterase-EGFP(+) mice were treated with cuprizone, and OPCs were sorted from the corpus callosum. Microarray analysis revealed that Sfmbt2 family miRNAs decreased during cuprizone treatment. One particular Sfmbt2 miRNA, miR-297c-5p, increased during mouse OPC differentiation in vitro and during callosal development in vivo. When overexpressed in both mouse embryonic fibroblasts and rat OPCs (rOPCs), cell cycle analysis revealed that miR-297c-5p promoted G1/G0 arrest. Additionally, miR-297c-5p transduction increased the number of O1(+) rOPCs during differentiation. Luciferase reporter assays confirmed that miR-297c 5p targets cyclin T2 (CCNT2), the regulatory subunit of positive transcription elongation factor b, a complex that inhibits OL maturation. Furthermore, CCNT2 specific knockdown promoted rOPC differentiation while not affecting cell cycle status. Together, these data support a dual role for miR-297c-5p as both a negative regulator of OPC proliferation and a positive regulator of OL maturation via its interaction with CCNT2. SIGNIFICANCE STATEMENT: This work describes the role of oligodendrocyte progenitor cell (OPC) microRNAs (miRNAs) during remyelination and development in vivo and differentiation in vitro. This work highlights the importance of miRNAs to OPC biology and describes miR-297c-5p, a novel regulator of OPC function. In addition, we identified CCNT2 as a functional target, thus providing a mechanism by which miR-297c-5p imparts its effects on differentiation. These data are important, given our lack of understanding of OPC miRNA regulatory networks and their potential clinical value. Therefore, efforts to understand the role of miR-297c-5p in pathological conditions and its potential for facilitating repair may provide future therapeutic strategies to treat demyelination. PMID- 26843652 TI - Metabotropic Glutamate Receptors Induce a Form of LTP Controlled by Translation and Arc Signaling in the Hippocampus. AB - Activity-dependent bidirectional modifications of excitatory synaptic strength are essential for learning and storage on new memories. Research on bidirectional synaptic plasticity has largely focused on long-term potentiation (LTP) and long term depression (LTD) mechanisms that rely on the activation of NMDA receptors. In principle, metabotropic glutamate receptors (mGluRs) are also suitable to convert synaptic activity into intracellular signals for synaptic modification. Indeed, dysfunction of a form of LTD that depends on Type I mGluRs (mGluR-LTD), but not NMDARs, has been implicated in learning deficits in aging and mouse models of several neurological conditions, including Fragile X syndrome and Alzheimer's disease. To determine whether mGluR activation can also induce LTP in the absence of NMDAR activation, we examined in hippocampal slices from rats and mice, an NMDAR-independent form of LTP previously characterized as dependent on voltage-gated Ca(2+) channels. We found that this form of LTP requires activation of Type I mGluRs and, like mGluR-LTD but unlike NMDAR-dependent plasticity, depends crucially on protein synthesis controlled by fragile X mental retardation protein and on Arc signaling. Based on these observations, we propose the coexistence of two distinct activity-dependent systems of bidirectional synaptic plasticity: one that is based on the activity of NMDARs and the other one based on the activation of mGluRs. SIGNIFICANCE STATEMENT: Bidirectional changes of synaptic strength are crucial for the encoding of new memories. Currently, the only activity-dependent mechanism known to support such bidirectional changes are long-term potentiation (LTP) and long-term depression (LTD) forms that relay on the activation of NMDA receptors. Metabotropic glutamate receptors (mGluRs) are, in principle, also suitable to trigger bidirectional synaptic modifications. However, only the mGluR-dependent form of LTD has been characterized. Here we report that an NMDAR-independent form of LTP, initially characterized as dependent on voltage-gated Ca(2+) channels, also requires the activation of mGluRs. These finding suggest the coexistence of two distinct activity-dependent systems of bidirectional synaptic plasticity: one that is based on the activity of NMDARs and the other one based on the activation of mGluRs. PMID- 26843653 TI - Single-Cell Detection of Secreted Abeta and sAPPalpha from Human IPSC-Derived Neurons and Astrocytes. AB - Secreted factors play a central role in normal and pathological processes in every tissue in the body. The brain is composed of a highly complex milieu of different cell types and few methods exist that can identify which individual cells in a complex mixture are secreting specific analytes. By identifying which cells are responsible, we can better understand neural physiology and pathophysiology, more readily identify the underlying pathways responsible for analyte production, and ultimately use this information to guide the development of novel therapeutic strategies that target the cell types of relevance. We present here a method for detecting analytes secreted from single human induced pluripotent stem cell (iPSC)-derived neural cells and have applied the method to measure amyloid beta (Abeta) and soluble amyloid precursor protein-alpha (sAPPalpha), analytes central to Alzheimer's disease pathogenesis. Through these studies, we have uncovered the dynamic range of secretion profiles of these analytes from single iPSC-derived neuronal and glial cells and have molecularly characterized subpopulations of these cells through immunostaining and gene expression analyses. In examining Abeta and sAPPalpha secretion from single cells, we were able to identify previously unappreciated complexities in the biology of APP cleavage that could not otherwise have been found by studying averaged responses over pools of cells. This technique can be readily adapted to the detection of other analytes secreted by neural cells, which would have the potential to open new perspectives into human CNS development and dysfunction. SIGNIFICANCE STATEMENT: We have established a technology that, for the first time, detects secreted analytes from single human neurons and astrocytes. We examine secretion of the Alzheimer's disease-relevant factors amyloid beta (Abeta) and soluble amyloid precursor protein-alpha (sAPPalpha) and present novel findings that could not have been observed without a single-cell analytical platform. First, we identify a previously unappreciated subpopulation that secretes high levels of Abeta in the absence of detectable sAPPalpha. Further, we show that multiple cell types secrete high levels of Abeta and sAPPalpha, but cells expressing GABAergic neuronal markers are overrepresented. Finally, we show that astrocytes are competent to secrete high levels of Abeta and therefore may be a significant contributor to Abeta accumulation in the brain. PMID- 26843654 TI - Orexin Neurons Respond Differentially to Auditory Cues Associated with Appetitive versus Aversive Outcomes. AB - Orexin (Orx) neurons are known to be involved in the promotion and maintenance of waking because they discharge in association with cortical activation and muscle tone during waking and because, in their absence, waking with muscle tone cannot be maintained and narcolepsy with cataplexy ensues. Whether Orx neurons discharge during waking in association with particular conditions, notably with appetitive versus aversive stimuli or positive versus negative emotions, is debated and considered important in understanding their role in supporting particular waking behaviors. Here, we used the technique of juxtacellular recording and labeling in head-fixed rats to characterize the discharge of Orx neurons during the performance of an associative discrimination task with auditory cues for appetitive versus aversive outcomes. Of 57 active, recorded, and neurobiotin labeled neurons in the lateral hypothalamus, 11 were immunohistochemically identified as Orx-positive (Orx(+)), whereas none were identified as melanin concentrating hormone-positive. Orx(+) neurons discharged at significantly higher rates during the tone associated with sucrose than during the tone associated with quinine delivered upon licking. They also discharged at high rates after the tone associated with sucrose. Across periods and outcomes, their discharge was positively correlated with EEG gamma activity and EMG activity, which is indicative of cortical activation and behavioral arousal. These results suggest that Orx neurons discharge in a manner characteristic of reward neurons yet also characteristic of arousal neurons. Accordingly, the Orx neurons may respond to and participate in reward processes while modulating cortical activity and muscle tone to promote and maintain arousal along with learned adaptive behavioral responses. SIGNIFICANCE STATEMENT: Orexin neurons play a critical role in promoting and maintaining a waking state because, in their absence, narcolepsy with cataplexy ensues. Known to discharge during waking and not during sleep, they have also been proposed to be selectively active during appetitive behaviors. Here, we recorded and labeled neurons in rats to determine the discharge of immunohistochemically identified orexin neurons during performance of an associative discrimination task. Orexin neurons responded differentially to auditory cues associated with appetitive sucrose versus aversive quinine, indicating that they behave like reward neurons. However, correlated discharge with cortical and muscle activity indicates that they also behave like arousal neurons and can thus promote cortical activation with behavioral arousal and muscle tone during adaptive waking behaviors. PMID- 26843657 TI - Swain-Scott Relationships for Nucleophile Addition to Ring-Substituted Phenonium Ions. AB - The products of the reactions of 2-(4-methoxyphenyl)ethyl tosylate (MeO-1-Ts) and 2-(4-methyphenyl)ethyl tosylate (Me-1-Ts) with nucleophilic anions were determined for reactions in 50/50 (v/v) trifluoroethanol/water at 25 degrees C. In many cases the nucleophile selectivity kNu/ks (M-1) for reactions of nucleophile and solvent, calculated from the ratio of product yields, depends upon [Nu-]. This demonstrates the existence of competing reaction pathways, which show different selectivities for reactions with nucleophiles. A carbon-13 NMR analysis of the products of the reactions of substrate enriched with carbon-13 at the alpha-carbon, X-1-[alpha-13C]Ts, (X = -OCH3, -Me) with nucleophilic anions in 50/50 (v/v) trifluoroethanol/water at 25 degrees C shows the formation of X-1 [beta-13C]OH, X-1-[beta-13C]OCH2CF3 and X-1-[beta-13C]Nu (Nu = Br, Cl, CH3CO2, Cl2CHCO2) from the trapping of symmetrical 4-substituted phenonium ion reaction intermediates X-2+ . The observation of excess label in the alpha-position, [alpha-13C]/[beta-13C] > 1.0, for both the water and nucleophile adducts, shows that water and anionic nucleophiles also react by direct substitution at X-1 [alpha-13C]Ts. The ratios of product yields, [alpha-13C]/[beta-13C], and observed nucleophile selectivity (kNu/ks)obs were used to dissect the contribution of direct nucleophile addition at Me-1-Ts and trapping of X-2+ to the product yields. The product yields from partitioning of the intermediate gave the nucleophile selectivity kNu/ks (M-1) for X-2+ . Swain-Scott plots of log (kNu/ks) are correlated by slopes of s = 0.78 and s = 0.73 for reactions of MeO-2+ and Me 2+ , respectively. This shows that the sensitivity of bimolecular substitution at X-2+ to changes in nucleophile reactivity is smaller than for nucleophilic substitution at the methyl iodide. Evidence is presented that nucleophile addition to X-2+ proceeds through an "exploded" transition state. PMID- 26843656 TI - On the Structure of Neuronal Population Activity under Fluctuations in Attentional State. AB - Attention is commonly thought to improve behavioral performance by increasing response gain and suppressing shared variability in neuronal populations. However, both the focus and the strength of attention are likely to vary from one experimental trial to the next, thereby inducing response variability unknown to the experimenter. Here we study analytically how fluctuations in attentional state affect the structure of population responses in a simple model of spatial and feature attention. In our model, attention acts on the neural response exclusively by modulating each neuron's gain. Neurons are conditionally independent given the stimulus and the attentional gain, and correlated activity arises only from trial-to-trial fluctuations of the attentional state, which are unknown to the experimenter. We find that this simple model can readily explain many aspects of neural response modulation under attention, such as increased response gain, reduced individual and shared variability, increased correlations with firing rates, limited range correlations, and differential correlations. We therefore suggest that attention may act primarily by increasing response gain of individual neurons without affecting their correlation structure. The experimentally observed reduction in correlations may instead result from reduced variability of the attentional gain when a stimulus is attended. Moreover, we show that attentional gain fluctuations, even if unknown to a downstream readout, do not impair the readout accuracy despite inducing limited-range correlations, whereas fluctuations of the attended feature can in principle limit behavioral performance. SIGNIFICANCE STATEMENT: Covert attention is one of the most widely studied examples of top-down modulation of neural activity in the visual system. Recent studies argue that attention improves behavioral performance by shaping of the noise distribution to suppress shared variability rather than by increasing response gain. Our work shows, however, that latent, trial-to-trial fluctuations of the focus and strength of attention lead to shared variability that is highly consistent with known experimental observations. Interestingly, fluctuations in the strength of attention do not affect coding performance. As a consequence, the experimentally observed changes in response variability may not be a mechanism of attention, but rather a side effect of attentional allocation strategies in different behavioral contexts. PMID- 26843655 TI - Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability. AB - Newborn neurons enter an extended maturation stage, during which they acquire excitability characteristics crucial for development of presynaptic and postsynaptic connectivity. In contrast to earlier specification programs, little is known about the regulatory mechanisms that control neuronal maturation. The Pet-1 ETS (E26 transformation-specific) factor is continuously expressed in serotonin (5-HT) neurons and initially acts in postmitotic precursors to control acquisition of 5-HT transmitter identity. Using a combination of RNA sequencing, electrophysiology, and conditional targeting approaches, we determined gene expression patterns in maturing flow-sorted 5-HT neurons and the temporal requirements for Pet-1 in shaping these patterns for functional maturation of mouse 5-HT neurons. We report a profound disruption of postmitotic expression trajectories in Pet-1(-/-) neurons, which prevented postnatal maturation of 5-HT neuron passive and active intrinsic membrane properties, G-protein signaling, and synaptic responses to glutamatergic, lysophosphatidic, and adrenergic agonists. Unexpectedly, conditional targeting revealed a postnatal stage-specific switch in Pet-1 targets from 5-HT synthesis genes to transmitter receptor genes required for afferent modulation of 5-HT neuron excitability. Five-HT1a autoreceptor expression depended transiently on Pet-1, thus revealing an early postnatal sensitive period for control of 5-HT excitability genes. Chromatin immunoprecipitation followed by sequencing revealed that Pet-1 regulates 5-HT neuron maturation through direct gene activation and repression. Moreover, Pet-1 directly regulates the 5-HT neuron maturation factor Engrailed 1, which suggests Pet-1 orchestrates maturation through secondary postmitotic regulatory factors. The early postnatal switch in Pet-1 targets uncovers a distinct neonatal stage specific function for Pet-1, during which it promotes maturation of 5-HT neuron excitability. SIGNIFICANCE STATEMENT: The regulatory mechanisms that control functional maturation of neurons are poorly understood. We show that in addition to inducing brain serotonin (5-HT) synthesis and reuptake, the Pet-1 ETS (E26 transformation-specific) factor subsequently globally coordinates postmitotic expression trajectories of genes necessary for maturation of 5-HT neuron excitability. Further, Pet-1 switches its transcriptional targets as 5-HT neurons mature from 5-HT synthesis genes to G-protein-coupled receptors, which are necessary for afferent synaptic modulation of 5-HT neuron excitability. Our findings uncover gene-specific switching of downstream targets as a previously unrecognized regulatory strategy through which continuously expressed transcription factors control acquisition of neuronal identity at different stages of development. PMID- 26843658 TI - Genetic diversity of the NE Atlantic sea urchin Strongylocentrotus droebachiensis unveils chaotic genetic patchiness possibly linked to local selective pressure. AB - We compared the genetic differentiation in the green sea urchin Strongylocentrotus droebachiensis from discrete populations on the NE Atlantic coast. By using eight recently developed microsatellite markers, genetic structure was compared between populations from the Danish Strait in the south to the Barents Sea in the north (56-79 degrees N). Urchins are spread by pelagic larvae and may be transported long distances by northwards-going ocean currents. Two main superimposed patterns were identified. The first showed a subtle but significant genetic differentiation from the southernmost to the northernmost of the studied populations and could be explained by an isolation by distance model. The second pattern included two coastal populations in mid-Norway (65 degrees N), NH and NS, as well as the northernmost population of continental Norway (71 degrees N) FV. They showed a high degree of differentiation from all other populations. The explanation to the second pattern is most likely chaotic genetic patchiness caused by introgression from another species, S. pallidus, into S. droebachiensis resulting from selective pressure. Ongoing sea urchin collapse and kelp forests recovery are observed in the area of NH, NS and FV populations. High gene flow between populations spanning more than 22 degrees in latitude suggests a high risk of new grazing events to occur rapidly in the future if conditions for sea urchins are favourable. On the other hand, the possibility of hybridization in association with collapsing populations may be used as an early warning indicator for monitoring purposes. PMID- 26843660 TI - Evidence of Support for Smoke-Free Public Housing Among New York City Residents. PMID- 26843662 TI - HRSA's Transformation of Public Health Training. PMID- 26843663 TI - The Shift to High-Impact HIV Prevention by Health Departments in the United States. PMID- 26843666 TI - Hepatitis A Infections Among Food Handlers in the United States, 1993-2011. AB - We reviewed news reports of hepatitis A virus (HAV)-infected food handlers in the United States from 1993 to 2011 using the LexisNexis(r) search engine. Using U.S. news reports, we identified 192 HAV-infected food handlers who worked while infectious; of these HAV-infected individuals, 34 (18%) transmitted HAV to restaurant patrons. News reports of HAV-infected food handlers declined from 1993 to 2011. This analysis suggests that universal childhood vaccination contributed to the decrease in reports of HAV-infected food handlers, but mandatory vaccination of this group is unlikely to be cost-effective. PMID- 26843665 TI - Overcoming Barriers to Low HPV Vaccine Uptake in the United States: Recommendations from the National Vaccine Advisory Committee: Approved by the National Vaccine Advisory Committee on June 9, 2015. PMID- 26843664 TI - A Call for Greater Consideration for the Role of Vaccines in National Strategies to Combat Antibiotic-Resistant Bacteria: Recommendations from the National Vaccine Advisory Committee: Approved by the National Vaccine Advisory Committee on June 10, 2015. PMID- 26843667 TI - Using a Handheld Device for Patient Data Collection: A Pilot for Medical Countermeasures Surveillance. AB - Medical countermeasures (MCMs) are medical products used during public health emergencies. This study, conducted within the Mini-Sentinel Initiative, sought to develop the patient identification and matching processes necessary to assess safety outcomes for MCMs. A handheld device was used to collect identifying information (e.g., name, birthdate, and sex) from the driver's licenses of 421 individuals presenting for routine care at their primary care medical office. Overall, 374 individuals (88.8%) could be linked to their electronic health data using driver's license information. The device was also pilot-tested at a seasonal influenza immunization clinic: detailed vaccine information (e.g., lot number and manufacturer) was captured with a high degree of accuracy. This investigation demonstrated that a handheld device is a feasible means of collecting patient identity and medical product receipt data. This capacity should be useful for safety surveillance of MCMs, particularly when dispensed in settings outside the traditional health-care delivery system. PMID- 26843668 TI - A Tool for Providing Data on Small Areas: Development of Neighborhood Profiles for Santa Clara County, California, 2014. AB - Data on small geographic areas that can be easily accessed and updated have become essential for targeting public health programs and services. Disaggregating data at the sub-county or sub-city level has the potential to reveal disparities not otherwise evident for large geographies. As important as such data are, the methods to produce data on small geographic areas are challenging and resource-intensive, and little description and analysis of such tools exists. We describe a tool--neighborhood profiles--that provides a way for public health agencies and their partners to define neighborhood boundaries, select indicators, and disseminate data in a user-friendly format. We also share lessons learned, including the importance of involving planning departments in boundary definition to ensure relevance to the community, selecting a framework that links indicators to broader conceptual categories that can highlight disparities, and forming a team with the diverse skills necessary for planning and developing the profiles. PMID- 26843669 TI - Integrating Public Health and Deliberative Public Bioethics: Lessons from the Human Genome Project Ethical, Legal, and Social Implications Program. AB - Public health policy works best when grounded in firm public health standards of evidence and widely shared social values. In this article, we argue for incorporating a specific method of ethical deliberation--deliberative public bioethics--into public health. We describe how deliberative public bioethics is a method of engagement that can be helpful in public health. Although medical, research, and public health ethics can be considered some of what bioethics addresses, deliberative public bioethics offers both a how and where. Using the Human Genome Project Ethical, Legal, and Social Implications program as an example of effective incorporation of deliberative processes to integrate ethics into public health policy, we examine how deliberative public bioethics can integrate both public health and bioethics perspectives into three areas of public health practice: research, education, and health policy. We then offer recommendations for future collaborations that integrate deliberative methods into public health policy and practice. PMID- 26843671 TI - A Critical Assessment of Officially Reported Chagas Disease Surveillance Data in Mexico. AB - OBJECTIVE: Chagas disease, a disease caused by Trypanosoma cruzi, disproportionately affects poor people throughout Latin America. In Mexico, assessments of officially reported burden have not been previously reported. To evaluate discontinuity between surveillance data and data from other sources, we used data from the Mexican Ministry of Health to describe the distribution of reported Chagas disease over time in Mexico and compare it with estimates from the literature. METHODS: We summarized age and sex differences for Chagas cases and mortality for 1995-2013 and 1982-2010, respectively. We examined the spatial distribution of Chagas disease over time with respect to disease burden. We further compared officially reported figures with estimates from the literature. RESULTS: Among 6,494 officially reported cases, rates of Chagas disease were highest in adults aged 25-44 years (47.3%). Mortality was highest in adults aged >=45 years (423/495, 85.5%). The data indicated increasing temporal trends for incidence and mortality. The greatest burden occurred in southern states, with increasing spatial distribution over time. Fewer than 900 cases and 40 deaths were officially reported annually, in contrast to estimates from the literature of approximately 69,000 new cases and 25,000 deaths annually. CONCLUSION: While increasing trends in officially reported data have been observed, large discrepancies in case estimates compromise our understanding of Chagas disease epidemiology. Reported cases based on current practices are not enough to correctly assess the Chagas disease burden and spatial distribution in Mexico. Understanding the true epidemiology of this disease will lead to more focused and successful control and prevention strategies to decrease disease burden. PMID- 26843672 TI - Evaluation Framework for HIV Prevention and Care Activities in the Enhanced Comprehensive HIV Prevention Planning Project, 2010-2013. AB - OBJECTIVE: The Enhanced Comprehensive HIV Prevention Planning (ECHPP) project was a demonstration project implemented by 12 U.S. health departments (2010-2013) to enhance HIV program planning in cities with high AIDS prevalence, in support of National HIV/AIDS Strategy goals. Grantees were required to improve their planning and implementation of HIV prevention and care programs to increase their impact on local HIV epidemics. A multilevel evaluation using multiple data sources, spanning multiple years (2008-2015), will be conducted to assess the effect of ECHPP on client outcomes (e.g., HIV risk behaviors) and impact indicators (e.g., new HIV diagnoses). METHODS: We designed an evaluation approach that includes a broad assessment of program planning and implementation, a detailed examination of HIV prevention and care activities across funding sources, and an analysis of environmental and contextual factors that may affect services. A data triangulation approach was incorporated to integrate findings across all indicators and data sources to determine the extent to which ECHPP contributed to trends in indicators. RESULTS: To date, data have been collected for 2008-2009 (pre-ECHPP implementation) and 2010-2013 (ECHPP period). Initial analysis of process data indicate the ECHPP grantees increased their provision of HIV testing, condom distribution, and partner services programs and expanded their delivery of prevention programs for people diagnosed with HIV. CONCLUSION: The ECHPP evaluation (2008-2015) will assess whether ECHPP programmatic activities in 12 areas with high AIDS prevalence contributed to changes in client outcomes, and whether these changes were associated with changes in longer-term, community-level impact. PMID- 26843670 TI - Shifting Resources and Focus to Meet the Goals of the National HIV/AIDS Strategy: The Enhanced Comprehensive HIV Prevention Planning Project, 2010-2013. AB - In September 2010, CDC launched the Enhanced Comprehensive HIV Prevention Planning (ECHPP) project to shift HIV-related activities to meet goals of the 2010 National HIV/AIDS Strategy (NHAS). Twelve health departments in cities with high AIDS burden participated. These 12 grantees submitted plans detailing jurisdiction-level goals, strategies, and objectives for HIV prevention and care activities. We reviewed plans to identify themes in the planning process and initial implementation. Planning themes included data integration, broad engagement of partners, and resource allocation modeling. Implementation themes included organizational change, building partnerships, enhancing data use, developing protocols and policies, and providing training and technical assistance for new and expanded activities. Pilot programs also allowed grantees to assess the feasibility of large-scale implementation. These findings indicate that health departments in areas hardest hit by HIV are shifting their HIV prevention and care programs to increase local impact. Examples from ECHPP will be of interest to other health departments as they work toward meeting the NHAS goals. PMID- 26843674 TI - Associations Between Social Determinants of Health and Pregnancy Among Young People: A Systematic Review of Research Published During the Past 25 Years. AB - OBJECTIVE: Major health disparities exist in pregnancy among young people. Although social determinant of health (SDH) approaches in interventions are promoted to reduce these disparities, little research exists that synthesizes empirical links between SDHs and pregnancy among young people. This systematic literature review utilized the Healthy People 2020 SDH framework to analyze and synthesize the empirical associations between SDHs and pregnancy among young people. METHODS: We included studies that were published in the past 25 years from PubMed, PsycINFO(r), and Academic Search" Premier databases. Twenty-two studies met all inclusion criteria and, following the Matrix Method, were assessed for methodological quality and empirical links between determinant areas and pregnancy. RESULTS: Seventeen studies reported an empirical association between at least one SDH and pregnancy among young people. Areas most represented were poverty and family structure. No studies examined the relationship between pregnancies among young people and quality of housing, access to healthy foods, access to health-care services and primary care, health technology, social cohesion, perceptions of discrimination/equity, access to employment, employment status, school policies that support health promotion, safe school environments, or higher education enrollment. CONCLUSION: This research indicates a need to expand the range of SDHs that are analyzed with pregnancy among young people and to focus interventions on areas that have been determined to have an empirical link with pregnancy. PMID- 26843673 TI - Systematic Review and Meta-Analysis of Inhaled Toxicants from Waterpipe and Cigarette Smoking. AB - OBJECTIVE: Waterpipe tobacco smoking (WTS) is an emerging trend worldwide. To inform public health policy and educational programming, we systematically reviewed the biomedical literature to compute the inhaled smoke volume, nicotine, tar, and carbon monoxide (CO) associated with a single WTS session and a single cigarette. METHODS: We searched seven biomedical bibliographic databases for controlled laboratory or natural environment studies designed to mimic human tobacco consumption. Included studies quantified the mainstream smoke of a single cigarette and/or single WTS session for smoke volume, nicotine, tar, and/or CO. We conducted meta-analyses to calculate summary estimates for the inhalation of each unique substance for each mode of tobacco consumption. We assessed between study heterogeneity using chi-squared and I-squared statistics. RESULTS: Sufficient data from 17 studies were available to derive pooled estimates for inhalation of each exposure via each smoking method. Two researchers working independently abstracted measurement of smoke volume in liters, and nicotine, tar, and CO in milligrams. All numbers included in meta-analyses matched precisely between the two researchers (100% agreement, Cohen's k=1.00). Whereas one WTS session was associated with 74.1 liters of smoke inhalation (95% confidence interval [CI] 38.2, 110.0), one cigarette was associated with 0.6 liters of smoke (95% CI 0.5, 0.7). One WTS session was also associated with higher levels of nicotine, tar, and CO. CONCLUSIONS: One WTS session consistently exposed users to larger smoke volumes and higher levels of tobacco toxicants compared with one cigarette. These computed estimates may be valuable to emphasize in prevention programming. PMID- 26843675 TI - Exposure to Suicide in the Community: Prevalence and Correlates in One U.S. State. AB - OBJECTIVE: Suicide has been identified as a major public health issue. Exposure to suicide (i.e., knowing someone who died by suicide) is far more pervasive than previously considered and might be associated with significant adverse outcomes. As suicide becomes more commonly discussed in the public arena, a compelling need exists to determine who is exposed to suicide and how this exposure affects those left behind. This study estimated the proportion of the population exposed to suicide and delineated factors that predict significant psychiatric and psychosocial morbidity following that exposure. METHODS: A dual-frame random digit-dial survey was conducted on a sample of 1,736 U.S. adults in the Commonwealth of Kentucky. Depression and anxiety were compared in suicide-exposed and suicide-unexposed individuals. Relationships were examined between psychiatric outcomes and perceptions of closeness to the decedent. RESULTS: Forty eight percent of weighted participants (n=816/1,687) reported lifetime exposure to suicide. Current depression and anxiety symptoms were higher in suicide exposed than in suicide-unexposed individuals. Suicide-exposed individuals were twice as likely as suicide-unexposed individuals to have diagnosable depression and almost twice as likely to have diagnosable anxiety. Suicide-exposed individuals were more likely than suicide-unexposed individuals to report suicide ideation (9% vs. 5%). Closeness to the decedent increased the odds of depression and anxiety and almost quadrupled the odds of posttraumatic stress disorder. CONCLUSION: Exposure to suicide is pervasive and occurs beyond family; as such, it is imperative to identify those with perceived closeness to the decedent. This hidden cohort of suicide-exposed people is at elevated risk for psychopathology and suicidal ideation. PMID- 26843676 TI - Needs Assessment for Patients with Sickle Cell Disease in South Carolina, 2012. AB - OBJECTIVE: We conducted a needs assessment for patients with sickle cell disease (SCD) in South Carolina using statewide administrative data to examine acute care utilization during a defined 12-month period. The data were collected to provide information for state and regional service providers, managed care companies, and policy makers to identify demographic gaps in care and inform policy and educational efforts to improve care. METHODS: We obtained records on emergency department visits and hospitalizations through patient-based uniform billing data. We stratified analyses of acute care utilization and 30-day readmission rates by patient age, region, and expected payer. RESULTS: Young adults, those with public insurance, and those who resided in a region with the largest number of patients had the highest rates of acute care utilization and 30-day readmissions. Patients who resided in a largely rural area without access to comprehensive care also had high rates of acute care utilization and readmissions. The pattern of readmissions data suggested that data on 7- or 14 day readmission rates, in addition to data on 30-day readmission rates, could be used as benchmarks of quality of care for adult patients with SCD. CONCLUSION: Administrative datasets can provide important information on demographic gaps in care for patients with SCD. The results highlight both national and regional issues in the provision of health-care services for patients with SCD. PMID- 26843677 TI - Evaluating Shared Laboratory Services: Detecting Mycobacterium Tuberculosis Complex and Drug Resistance Using Molecular and Culture-Based Methods. AB - OBJECTIVES: We explored sharing nucleic acid amplification testing (NAAT) for detection of Mycobacterium tuberculosis complex (MTBC) and molecular and phenotypic drug susceptibility testing between two state public health tuberculosis (TB) laboratories, and evaluated turnaround times and cost effectiveness. METHODS: From September 1, 2012, to May 30, 2013, the Wisconsin State Laboratory of Hygiene (Wisconsin Lab) submitted specimens to the Microbial Diseases Laboratory of the California Department of Public Health (California Lab) for NAAT and molecular drug susceptibility testing (MDST) by pyrosequencing, and culture-based TB drug susceptibility testing by the BACTEC(TM) MGIT(TM) 960 system. RESULTS: A total of 182 specimens were referred to the California Lab, and 47 TB cases and 12 drug-resistant cases were identified. The average time for specimen transport was two days, which included one day for processing and packaging in the submitting laboratory. The average turnaround time for NAAT was 0.3 days at the Wisconsin Lab and 3.8 days at the California Lab, including time for specimen transport. Turnaround time for culture-based drug susceptibility testing increased by a median of 16 days when specimens were sent to the California Lab, but MDST results were reported in fewer than four days, a median of 22 days sooner than any culture-based drug susceptibility testing results. CONCLUSION: This study revealed advantages and disadvantages associated with sharing services, and identified opportunities for improvement. Referral of specimens resulted in longer turnaround times for mycobacteriology test results and additional costs for transporting specimens. However, specialized testing such as pyrosequencing may not be available in low TB incidence areas, and these rapid results can have positive effects on patient management and TB control. PMID- 26843678 TI - Evaluating Early Case Capture of Pediatric Cancers in Seven Central Cancer Registries in the United States, 2013. AB - OBJECTIVE: Cancer is the second-leading cause of death in children, but incidence data are not available until two years after diagnosis, thereby delaying data dissemination and research. An early case capture (ECC) surveillance program was piloted in seven state cancer registries to register pediatric cancer cases within 30 days of diagnosis. We sought to determine the quality of ECC data and understand pilot implementation. METHODS: We used quantitative and qualitative methods to evaluate ECC. We assessed data quality by comparing demographic and clinical characteristics from the initial ECC submission to a resubmission of ECC pilot data and to the most recent year of routinely collected cancer data for each state individually and in aggregate. We conducted telephone focus groups with registry staff to determine ECC practices and difficulties in August and September 2013. Interviews were recorded, transcribed, and coded to identify themes. RESULTS: Comparing ECC initial submissions with submissions for all states, ECC data were nationally representative for age (9.7 vs. 9.9 years) and sex (673 of 1,324 [50.9%] vs. 42,609 of 80,547 [52.9%] male cases), but not for primary site (472 of 1,324 [35.7%] vs. 27,547 of 80,547 [34.2%] leukemia/lymphoma cases), behavior (1,219 of 1,324 [92.1%] vs. 71,525 of 80,547 [88.8%] malignant cases), race/ethnicity (781 of 1,324 [59.0%] vs. 64,518 of 80,547 [80.1%] white cases), or diagnostic confirmation (1,233 of 1,324 [93.2%] vs. 73,217 of 80,547 [90.9%] microscopically confirmed cases). When comparing initial ECC data with resubmission data, differences were seen in race/ethnicity (808 of 1,324 [61.1%] vs. 1,425 of 1,921 [74.2%] white cases), primary site (475 of 1,324 [35.9%] vs. 670 of 1,921 [34.9%] leukemia/lymphoma cases), and behavior (1,215 of 1,324 [91.8%] vs. 1,717 of 1,921 [89.4%] malignant cases). Common themes from focus group analysis included implementation challenges and facilitators, benefits of ECC, and utility of ECC data. CONCLUSIONS: ECC provided data rapidly and reflected national data overall with differences in several data elements. ECC also expanded cancer reporting infrastructure and increased data completeness and timeliness. Although challenges related to timeliness and increased work burden remain, indications suggest that researchers may reliably use these data for pediatric cancer studies. PMID- 26843679 TI - HIV Testing in Publicly Funded Settings, National Health Interview Survey, 2003 2010. AB - OBJECTIVE: We determined whether or not HIV testing in publicly funded settings in the United States increased after 2006, when CDC recommended expanded HIV screening in health-care settings for all people aged 13-64 years. METHODS: We analyzed 2003-2010 National Health Interview Survey data to estimate annual national percentages of people aged 18-64 years who were tested for HIV in the previous 12 months. Estimates were calculated by setting (publicly funded, yes/other) and stratified by sex. Test settings were categorized as publicly funded based on the contribution of public funds for HIV testing. We used logistic regression modeling to assess statistical significance in linear trends for 2003-2006 and 2006-2010, adjusting for age, race/ethnicity, and health insurance coverage. Using model parameters for survey year, we calculated the estimated annual percentage change (EAPC) in HIV testing as the difference in the model-predicted testing prevalence between baseline and first post-baseline years, divided by baseline prevalence. RESULTS: During 2006-2010, the percentage of women tested for HIV in publicly funded settings increased significantly from 1.9% in 2006 to 2.4% in 2010 (EAPC=6.9%, p=0.008) and the percentage tested in other settings remained fairly stable, from 9.7% in 2006 to 9.6% in 2010 (EAPC= 0.5%, p=0.708). During the same period, the percentage of men tested for HIV in publicly funded settings increased, but not significantly, from 1.5% in 2006 to 1.9% in 2010 (EAPC=5.3%, p=0.110) and the percentage tested in other settings decreased significantly from 7.5% in 2006 to 6.2% in 2010 (EAPC=-4.4%, p=0.001). CONCLUSION: Although HIV testing in publicly funded settings increased among women during 2006-2010, testing rates remained low, and no similar increase occurred among men. As such, all test settings should increase HIV screening, particularly for men. PMID- 26843680 TI - The Public Health Nurse Workforce in U.S. State and Local Health Departments, 2012. AB - OBJECTIVE: Public health nurses (PHNs) represent the single largest group of public health practitioners working in U.S. state and local health departments. Despite the important role of PHNs in the delivery and administration of public health services, little research has been conducted on this group and relatively little is known about PHN education, training, and retirement intentions. We describe the findings of a nationally representative survey of PHNs working in state and local health departments by characterizing their educational background and plans for retirement. METHODS: An advisory committee convened by the University of Michigan Center of Excellence in Public Health Workforce Studies developed the Public Health Nurse Workforce Survey and disseminated it in 2012 to 50 U.S. state and 328 local health departments. RESULTS: The 377 responding state and local health departments reported an estimated 34,521 full-time equivalent registered nurses in their employ, with PHNs or community health nurses as the largest group of workers (63%). Nearly 20% of state health department PHNs and 31% of local health department PHNs were educated at the diploma or associate's degree level. Approximately one-quarter of PHNs were determined to be eligible for retirement by 2016. Professional development and promotion opportunities, competitive benefits and salary, and hiring procedures were among the recruitment and retention issues reported by health departments. CONCLUSION: PHNs were reported to have highly variable occupational classifications and educational backgrounds in health departments. Additional training opportunities are needed for PHNs with diploma and associate's degrees. A shortage of PHNs is possible due to retirement eligibility and administrative barriers to recruitment and retention. PMID- 26843681 TI - Agreement Between Self-Reported and Confirmed Cancer Diagnoses in New York City Firefighters and EMS Workers, 2001-2011. AB - OBJECTIVES: Because of the delay in availability of cancer diagnoses from state cancer registries, self-reported diagnoses may be valuable in assessing the current cancer burden in many populations. We evaluated agreement between self reported cancer diagnoses and state cancer registry-confirmed diagnoses among 21,437 firefighters and emergency medical service workers from the Fire Department of the City of New York. We also investigated the association between World Trade Center (WTC) exposure and other characteristics in relation to accurate reporting of cancer diagnoses. METHODS: Participants self-reported cancer status in questionnaires from October 2, 2001, to December 31, 2011. We obtained data on confirmed cancer diagnoses from nine state cancer registries, which we used as our gold standard. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), comparing self-reported cancer diagnoses with confirmed cancer diagnoses. We used multivariable logistic regression models to assess the association between WTC exposure and correct self-report of cancer status, false-positive cancer reports, and false-negative cancer reports. RESULTS: Sensitivity and specificity for all cancers combined were 90.3% and 98.7%, respectively. Specificities and NPVs remained high in different cancer types, while sensitivities and PPVs varied considerably. WTC exposure was not associated with accurate reporting. CONCLUSION: We found high specificities, NPVs, and general concordance between self-reported cancer diagnoses and registry-confirmed diagnoses. Given the low population prevalence of cancer, self-reported cancer diagnoses may be useful for determining non-cancer cases. Because of the low sensitivities and PPVs for some individual cancers, however, case confirmation with state cancer registries or medical records remains critically important. PMID- 26843682 TI - The Impact of the Affordable Care Act on Funding for Newborn Screening Services. AB - OBJECTIVE: The Affordable Care Act requires most health plans to cover the federal Recommended Uniform Screening Panel of newborn screening (NBS) tests with no cost sharing. However, state NBS programs vary widely in both the number of mandated tests and their funding mechanisms, including a combination of state laboratory fees, third-party billing, and other federal and state funding. We assessed the potential impact of the Affordable Care Act coverage mandate on states' NBS funding. METHOD: We performed an extensive review of the refereed literature, federal and state agency reports, relevant organizations' websites, and applicable state laws and regulations; interviewed 28 state and federal officials from August to December 2014; and then assessed the interview findings manually. RESULTS: Although a majority of states had well-established systems for including laboratory-based NBS tests in bundled charges for newborn care, billing practices for critical congenital heart disease and newborn hearing tests were less uniform. Most commonly, birthing facilities either prepaid the costs of laboratory-based tests when acquiring the filter paper kits, or the facilities paid for the tests when the kits were submitted. Some states had separate arrangements for billing Medicaid, and smaller facilities sometimes contracted with hearing test vendors that billed families separately. CONCLUSION: Although the Affordable Care Act coverage mandate may offset some state NBS funding for the screenings themselves, federal support is still required to assure access to the full range of NBS program services. Limiting reimbursement to the costs of screening tests alone would undermine the common practice of using screening charges to fund follow-up services counseling, and medical food or formula, particularly for low-income families. PMID- 26843683 TI - Prevalence of Diabetes and Health-Related Quality of Life Among Rural-to-Urban Nong Zhuan Fei Migrants in an Urban Area of Northern China, 2013. AB - OBJECTIVE: In China's Nong Zhuan Fei (NZF) communities, farmers living in rural villages are uprooted and moved into newly constructed urban apartments when the government purchases their land for residential and commercial development. With their relocation from a traditional rural setting to a modern urban setting, residents of NZF communities face lifestyle-based risk factors for diabetes and other chronic diseases. We reported estimates of diabetes prevalence, risk factors, and health-related quality of life among adult Chinese NZF rural-to urban migrants. METHODS: We conducted a descriptive cross-sectional study through a U.S.-China partnership with an NZF community of 3,184 residents. Health and disease history, risk factors, and sociodemographic information were collected by questionnaire. Participants completed a 24-hour diet recall, three-day physical activity recall, a health-related quality of life Short-Form 36 (SF-36) health survey, the Beck Depression Inventory, and fasting blood glucose tests. RESULTS: We gathered complete data from 1,150 of 1,772 eligible participants. The prevalence of diabetes was 11.6% (95% confidence interval 9.8, 13.6). Diabetes risk increased significantly with age, income, obesity, and hypertension. Based on SF-36 scores, residents aged >=60 years with diabetes reported significantly greater physical (47.7 v. 70.2, p=0.001) and emotional (76.9 vs. 89.7, p=0.006) limitations, more bodily pain (79.7 vs. 84.9, p=0.021), and worse overall physical health (67.6 vs. 76.0, p=0.015) than those without diabetes. CONCLUSION: The Chinese government hopes to integrate an additional 250 million people into city living by 2025. As the NZF population increases, so may the prevalence of diabetes associated with the change from a rural to an urban lifestyle. Action is needed now by public health professionals to prevent a possible diabetes crisis in NZF communities in the future. PMID- 26843684 TI - Population-Based Estimates of Decreases in Quality-Adjusted Life Expectancy Associated with Unhealthy Body Mass Index. AB - OBJECTIVE: Being classified as outside the normal range for body mass index (BMI) has been associated with increased risk for chronic health conditions, poor health-related quality of life (HRQOL), and premature death. To assess the impact of BMI on HRQOL and mortality, we compared quality-adjusted life expectancy (QALE) by BMI levels. METHODS: We obtained HRQOL data from the 1993-2010 Behavioral Risk Factor Surveillance System and life table estimates from the National Center for Health Statistics national mortality files to estimate QALE among U.S. adults by BMI categories: underweight (BMI <18.5 kg/m(2)), normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25.0-29.9 kg/m(2)), obese (BMI 30.0-34.9 kg/m(2)), and severely obese (BMI >=35.0 kg/m(2)). RESULTS: In 2010 in the United States, the highest estimated QALE for adults at 18 years of age was 54.1 years for individuals classified as normal weight. The two lowest QALE estimates were for those classified as either underweight (48.9 years) or severely obese (48.2 years). For individuals who were overweight or obese, the QALE estimates fell between those classified as either normal weight (54.1 years) or severely obese (48.2 years). The difference in QALE between adults classified as normal weight and those classified as either overweight or obese was significantly higher among women than among men, irrespective of race/ethnicity. CONCLUSIONS: Using population-based data, we found significant differences in QALE loss by BMI category. These findings are valuable for setting national and state targets to reduce health risks associated with severe obesity, and could be used for cost-effectiveness evaluations of weight-reduction interventions. PMID- 26843685 TI - Health Department HIV Prevention Programs That Support the National HIV/AIDS Strategy: The Enhanced Comprehensive HIV Prevention Planning Project, 2010-2013. AB - OBJECTIVE: The Enhanced Comprehensive HIV Prevention Planning project was the first initiative of the Centers for Disease Control and Prevention (CDC) to address the goals of the National HIV/AIDS Strategy (NHAS). Health departments in 12 U.S. cities with a high prevalence of AIDS conducted comprehensive program planning and implemented cost-effective, scalable HIV prevention interventions that targeted high-risk populations. We examined trends in health department HIV prevention programs in these cities during the project. METHODS: We analyzed the number of people who received partner services, condoms distributed, and people tested for HIV, as well as funding allocations for selected HIV prevention programs by year and by site from October 2010 through September 2013. We assessed trends in the proportional change in services and allocations during the project period using generalized estimating equations. We also conducted thematic coding of program activities that targeted people living with HIV infection (PLWH). RESULTS: We found significant increases in funding allocations for HIV testing and condom distribution. All HIV partner services indicators, condom distribution, and HIV testing of African American and Hispanic/Latino populations significantly increased. HIV tests associated with a new diagnosis increased significantly among those self-identifying as Hispanic/Latino but significantly decreased among African Americans. For programs targeting PLWH, health department activities included implementing new program models, improving local data use, and building local capacity to enhance linkage to HIV medical care, retention in care, and treatment adherence. CONCLUSIONS: Overall, these findings indicate that health departments in areas with a high burden of AIDS successfully shifted their HIV prevention resources to scale up important HIV programs and make progress toward NHAS goals. PMID- 26843687 TI - Tax-Exempt Hospitals and Community Health Under the Affordable Care Act: Identifying and Addressing Unmet Legal Needs as Social Determinants of Health. PMID- 26843689 TI - Flipping the Classroom and the Pedagogy: Using Active Learning Principles to Bring Leadership Training in Affirmative Sexuality to Public Health Education. PMID- 26843690 TI - Mental Health Training in Schools of Public Health: History, Current Status, and Future Opportunities. PMID- 26843691 TI - Erratum. PMID- 26843694 TI - Microbiological Analyses of Traditional Alcoholic Beverage (Chhang) and its Starter (Balma) Prepared by Bhotiya Tribe of Uttarakhand, India. AB - Present article depicts microbiology of starter (Balma) used in traditional solid state fermentation of alcoholic beverage (Chhang) by Bhotiya tribe of Uttarakhand. It also highlights the importance of herbs in Balma preparation and kinetics of lactic acid and ethanol fermentation under Chhang preparation using Balma. Balma contains 214 * 10(6) cfu/g yeasts, 2.54 * 10(6) cfu/g lactic acid bacteria (LAB) and 1.4 * 10(6) cfu/g other mesophilic bacteria. ITS sequence analysis revealed a rich diversity of yeast comprising of Saccharomyces cerevisiae, Saccharomycopsis fibuligera and Saccharomycopsis malanga in Balma. 16S rDNA sequence analysis revealed Lactobacillus pentosus and Pediococcus pentosaceus among LAB, while amylolytic Bacillus subtilis and B. aerophilus among other bacteria in Balma. Based on the results, it is speculated that herbs such as Inula cuspidata, Micromeria biflora, Origanum vulgare, Rubus sp. and Thymus linearis used earlier by Bhotiya in Balma preparation contribute as a source of yeasts, LAB and amylolytic bacilli. Study also demonstrates that Bhotiya tribe is rational in preparation of starter as they have circumvented the need of plants by using previous year Balma as inoculum and possibility of deficient quality of Balma due to weak colonization of phyllosphere and rhizosphere microbiota. Results suggest that simultaneous saccharification and lactic acid-ethanol fermentation take place in traditional cereal based Chhang fermentation system of Bhotiya. PMID- 26843693 TI - Exploration of Modulated Genetic Circuits Governing Virulence Determinants in Staphylococcus aureus. AB - The expression of virulence genes in the human pathogen Staphylococcus aureus is strongly influenced by the multiple global regulators. The signal transduction cascade of these global regulators is accountable for recognizing and integrating the environmental cues to regulate the virulence regulon. While the production of virulent factors by individual global regulators are comparatively straightforward to define, auto-regulation of these global regulators and their impact on other regulators is more complex process. There are several reports on the production of virulent factors that are precisely regulated by switching processes of multiple global regulators including some prominent accessory regulators such as agr, sae and sar which allows S. aureus to coordinate the gene expression, and thus, provide organism an ability to act collectively. This review implicates the mechanisms involved in the global regulation of various virulence factors along with a comprehensive discussion on the differences between these signal transduction systems, their auto-induction and, coordination of classical and some comparatively new bacterial signal transduction systems. PMID- 26843692 TI - Potential Emergence of Multi-quorum Sensing Inhibitor Resistant (MQSIR) Bacteria. AB - Expression of certain bacterial genes only at a high bacterial cell density is termed as quorum-sensing (QS). Here bacteria use signaling molecules to communicate among themselves. QS mediated genes are generally involved in the expression of phenotypes such as bioluminescence, biofilm formation, competence, nodulation, and virulence. QS systems (QSS) vary from a single in Vibrio spp. to multiple in Pseudomonas and Sinorhizobium species. The complexity of QSS is further enhanced by the multiplicity of signals: (1) peptides, (2) acyl homoserine lactones, (3) diketopiperazines. To counteract this pathogenic behaviour, a wide range of bioactive molecules acting as QS inhibitors (QSIs) have been elucidated. Unlike antibiotics, QSIs don't kill bacteria and act at much lower concentration than those of antibiotics. Bacterial ability to evolve resistance against multiple drugs has cautioned researchers to develop QSIs which may not generate undue pressure on bacteria to develop resistance against them. In this paper, we have discussed the implications of the diversity and multiplicity of QSS, in acting as an arsenal to withstand attack from QSIs and may use these as reservoirs to develop multi-QSI resistance. PMID- 26843695 TI - Microbial Diversity in Soil, Sand Dune and Rock Substrates of the Thar Monsoon Desert, India. AB - A culture-independent diversity assessment of archaea, bacteria and fungi in the Thar Desert in India was made. Six locations in Ajmer, Jaisalmer, Jaipur and Jodhupur included semi-arid soils, arid soils, arid sand dunes, plus arid cryptoendolithic substrates. A real-time quantitative PCR approach revealed that bacteria dominated soils and cryptoendoliths, whilst fungi dominated sand dunes. The archaea formed a minor component of all communities. Comparison of rRNA defined community structure revealed that substrate and climate rather than location were the most parsimonious predictors. Sequence-based identification of 1240 phylotypes revealed that most taxa were common desert microorganisms. Semi arid soils were dominated by actinobacteria and alpha proteobacteria, arid soils by chloroflexi and alpha proteobacteria, sand dunes by ascomycete fungi and cryptoendoliths by cyanobacteria. Climatic variables that best explained this distribution were mean annual rainfall and maximum annual temperature. Substrate variables that contributed most to observed diversity patterns were conductivity, soluble salts, Ca(2+) and pH. This represents an important addition to the inventory of desert microbiota, novel insight into the abiotic drivers of community assembly, and the first report of biodiversity in a monsoon desert system. PMID- 26843697 TI - Augmentation of a Microbial Consortium for Enhanced Polylactide (PLA) Degradation. AB - Bioplastics are eco-friendly and derived from renewable biomass sources. Innovation in recycling methods will tackle some of the critical issues facing the acceptance of bioplastics. Polylactic acid (PLA) is the commonly used and well-studied bioplastic that is presumed to be biodegradable. Considering their demand and use in near future, exploration for microbes capable of bioplastic degradation has high potential. Four PLA degrading strains were isolated and identified as Penicillium chrysogenum, Cladosporium sphaerospermum, Serratia marcescens and Rhodotorula mucilaginosa. A consortium of above strains degraded 44 % (w/w) PLA in 30 days time in laboratory conditions. Subsequently, the microbial consortium employed effectively for PLA composting. PMID- 26843696 TI - A Genome-Wide Profiling Strategy as an Aid for Searching Unique Identification Biomarkers for Streptococcus. AB - The use of rrs (16S rRNA) gene is widely regarded as the "gold standard" for identifying bacteria and determining their phylogenetic relationships. Nevertheless, multiple copies of this gene in a genome is likely to give an overestimation of the bacterial diversity. In each of the 50 Streptococcus genomes (16 species, 50 strains), 4-7 copies of rrs are present. The nucleotide sequences of these rrs genes show high similarity within and among genomes, which did not allow unambiguous identification. A genome-wide search revealed the presence of 27 gene sequences common to all the Streptococcus species. Digestion of these 27 gene sequences with 10 type II restriction endonucleases (REs) showed that unique RE digestion in purH gene is sufficient for clear cut identification of 30 genomes belonging to 16 species. Additional gene-RE combinations allowed identification of another 15 strains belonging to S. pneumoniae, S. pyogenes, and S. suis. For the rest 5 strains, a combination of 2 genes was required for identifying them. The proposed strategy is likely to prove helpful in proper detection of pathogens like Streptococcus. PMID- 26843698 TI - Searching Biomarkers in the Sequenced Genomes of Staphylococcus for their Rapid Identification. AB - Bacterial identification using rrs (16S rRNA) gene is widely reported. Bacteria possessing multiple copies of rrs lead to overestimation of its diversity. Staphylococcus genomes carries 5-6 copies of rrs showing high similarity in their nucleotide sequences, which lead to ambiguous results. The genomes of 31 strains of Staphylococcus representing 7 species were searched for the presence of common genes. In silico digestion of 34 common genes using 10 restriction endonucleases (REs) lead to select gene-RE combinations, which could be used as biomarkers. RE digestion of recA allowed unambiguous identification of 13 genomes representing all the 7 species. In addition, a few more genes (argH, argR, cysS, gyrB, purH, and pyrE) and RE combinations permitted further identification of 12 strains. By employing additional RE and genes unique to a particular strain, it was possible to identify the rest 6 Staphylococcus aureus strains. This approach has the potential to be utilized for rapid detection of Staphylococcus strains. PMID- 26843699 TI - Preparation of Bacterial Cellulose/Inorganic Gel of Bentonite Composite by In Situ Modification. AB - To evaluate the possibility of Bacterial cellulose/Inorganic Gel of Bentonite (BC/IGB) composite production using in situ method, the BC/IGB composite was successfully produced by in situ modification of BC in both HS medium and corncob hydrolysate. The results showed that the BC/IGB composite obtained in HS medium (one classical medium for BC production) had a higher water holding capacity, but the water retention capacity of the BC/IGB composite obtained in corncob hydrolysate was better. The performance of BC/IGB composite depended on the environment of in situ modification. Using different media showed significant influence on the sugar utilization and BC yield. In addition, BC/IGB composite produced by in situ method was compared with that produced by ex situ method, and the results shows that water holding capacity of BC/IGB composite obtained through in situ method was better. XRD results showed the crystallinity of BC/IGB composite related little to its performance as water absorbent. Overall, in situ modification is appropriate for further production of BC composite and other clay materials. PMID- 26843701 TI - Thermostable Xanthine Oxidase Activity from Bacillus pumilus RL-2d Isolated from Manikaran Thermal Spring: Production and Characterization. AB - Xanthine oxidase is an important enzyme of purine metabolism that catalyzes the hydroxylation of hypoxanthine to xanthine and then xanthine to uric acid. A thermostable xanthine oxidase is being reported from a thermophilic organism RL 2d isolated from the Manikaran (Kullu) hot spring of Himachal Pradesh (India). Based on the morphology, physiological tests, and 16S rDNA gene sequence, RL-2d was identified as Bacillus pumilus. Optimization of physiochemical parameters resulted into 4.1-fold increase in the xanthine oxidase activity from 0.051 U/mg dcw (dry cell weight) to 0.209 U/mg dcw. The xanthine oxidase of B. pumilus RL-2d has exhibited very good thermostability and its t1/2 at 70 and 80 degrees C were 5 and 1 h, respectively. Activity of this enzyme was strongly inhibited by Hg(2+), Ag(+) and allopurinol. The investigation showed that B. pumilus RL-2d exhibited highest xanthine oxidase activity and remarkable thermostability among the other xanthine oxidases reported so far. PMID- 26843702 TI - Morphological and Molecular Characterization of Pomegranate Fruit Rot Pathogen, Chaetomella raphigera, and its Virulence Factors. AB - A new fungal pathogen was isolated from rotten pomegranates collected from the orchards of different parts of Maharashtra. The pathogen was morphologically identified as Chaetomella raphigera followed by sequencing of ITS and D1/D2 hypervariable region of LSU (28S) of rRNA gene. The pathogen produced pectinase, cellulase, xylanase and protease in liquid medium at a concentration of 71, 13.8, 54.3 and 7 U/ml respectively. Enzyme activity was also determined during pathogenesis in the tissues artificially infected by C. raphigera. Xylanase activity was maximum (25.1 U/g) followed by pectinase (19.2 U/g) and cellulase (1.5 U/g), whereas, protease activity was unnoticed. There was significant correlation (P < 0.05) between disease rating scale and pectinase, xylanase and cellulase activity in infected tissues. This indicates the simultaneous production of hydrolytic enzymes that aids in necrosis of fruit tissues. The elevated levels of these enzymes in infected tissues as compared with control suggest their possible role in pathogenesis. Thus, pectinase, cellulase and xylanase produced by C. raphigera acts as major virulence factors in the development of fruit rot in pomegranates. This is a first report of fungal fruit rot caused by C. raphigera in pomegranate. PMID- 26843700 TI - Factors Affecting Inducible Expression of Outer Membrane Protein A (OmpA) of Shigella dysenteriae Type-1 in Lactococcus lactis Using Nisin Inducible Controlled Expression (NICE). AB - Potential use of Lactococcus lactis (L. lactis) as a heterologous protein expression host as well as for delivery of multiple therapeutic proteins has been investigated extensively using Nisin Inducible Controlled Expression (NICE) system. Optimum inducible expression of heterologous protein by NICE system in L. lactis depends on multiple factors. To study the unexplored role of factors affecting heterologous protein expression in L. lactis using NICE, the present study outlines the optimization of various key parameters such as inducer concentration, host's proteases and precipitating agent using Outer membrane protein A (OmpA). For efficient expression and secretion of OmpA, pSEC:OmpA vector was successfully constructed. To circumvent the troubles encountered during detection of expressed OmpA, the precipitating agent was switched from TCA to methanol. Nevertheless, detection was achieved accompanied by degraded protein products. Speculating the accountability of observed degradation at higher inducer concentration, different nisin concentrations were evaluated. Lower nisin concentrations were found desirable for optimum expression of OmpA. Consistently observed degradation was eliminated by incorporation of protease inhibitor cocktail which inhibits intracellular proteases and expression in VEL1153 (NZ9000 DeltahtrA) strain which inhibits extracellular protease leading to optimum expression of OmpA. Versatility and complexity of NICE system in L. lactis requires fine-tuning of target protein specific parameters for optimum expression. PMID- 26843703 TI - Development of a Specific Diagnostic System for Detecting Turnip Yellow Mosaic Virus from Chinese Cabbage in Korea. AB - Turnip yellow mosaic virus (TYMV) is a plant pathogenic virus transmitted mainly through its host Brassica spp. TYMV is originated from Europe. Its infection cases have been reported in Australia, Brazil, Turkey, and Japan. Symptoms similar to those of TYMV infections were also reported in Korea in 2012. In this study, we developed RT-PCR primer pairs that were highly sensitive for detecting TYMV. The developed RT-PCR primer pairs offered about 10-100 times stronger detection sensitivity compared to primer pairs previously used in Korea. As a result, a 491 bp TYMV-specific band was identified. The specific band was confirmed to be TYMV based on sequencing results and phylogenetic analysis. The RT-PCR primer pairs developed in this study can be used to rapidly and precisely diagnose TYMV in agricultural products such as Chinese cabbage and other crops infected by TYMV. PMID- 26843704 TI - Development of Nested PCR-Based Specific Markers for Detection of Peach Rosette Mosaic Virus in Plant Quarantine. AB - The Peach rosette mosaic virus (PRMV) is a plant pathogen of the genus Nepovirus, and has been designated as a controlled quarantine virus in Korea. In this study, a specific reverse transcription (RT)-PCR marker set, nested PCR marker set, and modified-plasmid positive control were developed to promptly and accurately diagnose PRMV at plant-quarantine sites. The final selected PRMV-specific RT-PCR marker was PRMV-N10/C70 (967 bp), and the nested PCR product of 419 bp was finally amplified. The modified-plasmid positive control, in which the SalI restriction-enzyme region (GTCGAC) was inserted, verified PRMV contamination in a comparison with the control, enabling a more accurate diagnosis. It is expected that the developed method will continuously contribute to the plant-quarantine process in Korea. PMID- 26843706 TI - A tale of two contexts: U.S. migration and the labor force trajectories of Mexican women. AB - : Even though women have long participated in Mexico-U.S. migration studies assessing the labor market implications of international mobility for women are rare. Especially lacking are studies that follow a life-course approach and compare employment trajectories across contexts and in connection with other transitions. Using life-history data collected in Mexico and the United States, we explore the impact of migration on women's employment, focusing on how the determinants of employment vary across contexts. We show that U.S. residence eliminates or even reverses the employment returns to education found in Mexico, and that the constraints imposed on women's work by marriage are actually stronger in the U.S. CONTEXT: We also explicitly connect migration to other life course events, documenting how the impact of context varies not only by marital status but also by where women's unions were formed. PMID- 26843705 TI - The Effect of 9/11 on the Heritability of Political Trust. AB - Following the attacks of September 11, 2001, a rally effect led to a precipitous rise in political trust. However, the increase in political trust concealed a simultaneous decline among a smaller portion of the population. This paper examines the psychological mechanisms underlying these heterogeneous attitudes towards government and shows that a biosocial model best explains the observed patterns of response. The interplay of genetic and environmental factors of political trust reveals the stable but dynamic nature of heritability: genetic influences of political trust increased immediately following 9/11 but quickly decayed to pre-9/11 levels. PMID- 26843709 TI - Online pharmacies: a consumer perspective. PMID- 26843707 TI - Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients. AB - Celiac disease (CD), a gluten intolerance disorder, was implicated to have 57 genetic susceptibility loci for Europeans but not for culturally and geographically distinct ethnic populations like Saudi Arabian CD patients. Therefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Thr in MMEL1 genes. Single locus analysis identified that carriers of the 518 Thr/Thr (MMEL1) genotype conferred a 1.6-fold increased disease risk compared to the noncarriers (OR = 2.6; 95% CI: 1.22-5.54; P < 0.01). This significance persisted even under allelic (OR = 1.55; 95% CI: 1.05-2.28; P = 0.02) and additive (OR = 0.35; 95% CI: 0.17-0.71; P = 0.03) genetic models. However, frequencies for Trp262Arg (SH2B3) and Phe196Ser (IRAK1) polymorphisms were not significantly different between patients and controls. The overall best MDR model included Met518Thr and Trp262Arg polymorphisms, with a maximal testing accuracy of 64.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0156). Allelic distribution of the 518 Thr/Thr polymorphism in MMEL1 primarily suggests its independent and synergistic contribution towards CD susceptibility among Saudi patients. Lack of significant association of IRAK and SH2B3 gene polymorphisms in Saudi patients but their association in European groups suggests the genetic heterogeneity of CD. PMID- 26843708 TI - Online pharmacies: buyer beware. PMID- 26843710 TI - Concerns about quetiapine. PMID- 26843711 TI - Treating hepatitis C - what's new? AB - Chronic hepatitis C infection causes cirrhosis, liver failure and hepatocellular carcinoma, and is the most common indication for liver transplantation. Hepatitis C is curable and complications can be prevented. Until recently, treatment regimens involved peginterferon alfa. Although effective, their widespread use is limited by treatment-related toxicity. A number of direct-acting drugs for hepatitis C, such as sofosbuvir, have recently been developed and target multiple steps in the viral life cycle. These drugs are used in combination in interferon free regimens. Short courses are highly effective with minimal toxicity. PMID- 26843712 TI - Opioid prescribing pitfalls: medicolegal and regulatory issues. AB - Inappropriate opioid prescribing can lead to patient harm as well as a medicolegal risk to prescribers. Prescribers need to be familiar with the indications, contraindications and harms associated with opioids. When prescribing opioids, doctors must be aware of their clinical, ethical and legal responsibilities, particularly the legislative requirements in their state. Failure to comply with these can result in disciplinary action. To avoid potential conflict with differing state regulations on opioid prescribing, doctors should advise patients to get their prescription dispensed in the same state in which it was written. PMID- 26843713 TI - Updating the management of sexually transmitted infections. AB - The control of sexually transmitted infections relies on case-finding and treatment of sexual contacts to prevent further transmission. Screening for infections should be tailored to the demographic and sexual risk of the individual. For most sexually transmitted infections, screening is performed on self-collected, non-invasive samples using highly sensitive molecular assays. These are quick and inexpensive. Shorter courses of antivirals for genital herpes are now recommended. New chemoprophylactic strategies for preventing HIV transmission have emerged, including treatment to prevent transmission and the use of antiretrovirals for pre-exposure prophylaxis. PMID- 26843714 TI - Depression in dementia. AB - People with dementia of any type have a high incidence of major depression. The occurrence of a first major depressive episode in an older adult is a risk factor for developing dementia. Management of depression in a person with dementia should be enthusiastic with an aim to optimise quality of life. Non pharmacological and pharmacological strategies are both important in treating depression in dementia and management of these patients requires a collaborative approach. Selective serotonin reuptake inhibitors are the first-line pharmacotherapy for depression in dementia, although they are less likely to be effective in older people. PMID- 26843715 TI - Medicinal cannabis. AB - A number of therapeutic uses of cannabis and its derivatives have been postulated from preclinical investigations. Possible clinical indications include spasticity and pain in multiple sclerosis, cancer-associated nausea and vomiting, cancer pain and HIV neuropathy. However, evidence is limited, may reflect subjective rather than objective outcomes, and is not conclusive. Controversies lie in how to produce, supply and administer cannabinoid products. Introduction of cannabinoids therapeutically should be supported by a regulatory and educational framework that minimises the risk of harm to patients and the community. The Regulator of Medicinal Cannabis Bill 2014 is under consideration in Australia to address this. Nabiximols is the only cannabinoid on the Australian Register of Therapeutic Goods at present, although cannabidiol has been recommended for inclusion in Schedule 4. PMID- 26843716 TI - Medicines Australia Code of Conduct: breaches. PMID- 26843717 TI - Daclatasvir. PMID- 26843718 TI - Ledipasvir with sofosbuvir. PMID- 26843719 TI - Ponatinib. PMID- 26843720 TI - Tofacitinib. PMID- 26843721 TI - Vedolizumab. PMID- 26843722 TI - Australian Prescriber referees. PMID- 26843723 TI - Proximal Femoral Nail Antirotation in Treatment of Intertrochanteric Hip Fractures: a Retrospective Study in 113 Patients. AB - INTRODUCTION: The best treatment for intertrochanteric fractures remains controversial. Many methods have been recommended. AIM: We aimed to assess the results of osteosynthesis using the Proximal Femoral Nail Antirotation (PFNA) system. PATIENTS AND METHODS: We retrospectively analyzed 113 consecutive patients with intertrochanteric fractures treated with PFNA. Fractures were classified in accordance with the AO/OTA classification system into the groups A1, A2 and A3. The postoperative quality of fracture reduction was described as good, acceptable or poor. The location of the blade within the head was recorded as per the Cleveland method. Tip-apex distance (TAD) was used as a method for evaluating screw position. Pre-fracture and postoperative functional level were evaluated by the new mobility score (NMS). RESULTS: The average age at the time of surgery was 75.9 years. The majority, 75 (66.3 %), were unstable fracture types. The reduction was good in 67 (61.4 %) cases. Of the 24 deaths, 19 patients had comorbidities (p < 0.001). The number of deaths in the first 6 months was significantly higher than in the next 6 months (p = 0.001). The mean TAD was 25.6 mm. The Cleveland zone centre-centre was the most common placement of the blade, accounting for 33 (29 %) of the cases. Reoperation was required in four patients. There were four patients with cut-out. The pre-facture mean value NMS was 8.6 (SD 1.1) and the postoperative mean value was 4.3 (SD 3.6). CONCLUSION: We concluded that PFNA offers biomechanical advantages, but the best position of the blade is still unknown. PMID- 26843724 TI - The Effects of Drinking Coffee While Recovering from Colon and Rectal Resection Surgery. AB - AIM: Resection surgery on the colon and rectum are changing both anatomical and physiological relations within the abdominal cavity. Delayed functions of the gastrointestinal tract, flatulence, failure of peristalsis, prolonged spasms and pain, limited postoperative recovery of these patients increase the overall cost of treatment. Early consumption of coffee instead of tea should lead to faster restoration of normal function of the colon without unwanted negative repercussions. METHOD: This study is designed as a prospective-retrospective clinical study and was carried out at the Surgery Center Tuzla, during the year 2013/ 2014. Sixty patients were randomized in relation to the type of resection surgery, etiology of disease-malignant benign, and in relation to whether they were coffee users or not. Patients were divided into two groups. The first group of thirty patients was given 100 ml of instant coffee divided into three portions right after removing the nasogastric tube, first postoperative day, while the second group of thirty patients got 100 ml of tea. Monitored parameter was: time of first stool and the second group of monitored parameters was: whether there was returning of nasogastric tube or not, increased use of laxatives, whether there was anastomotic leak, radiologic and clinical dehiscence, audit procedures, or lethal outcomes in the treatment of patients. RESULTS: A total of 61 patients were randomized into two groups of 30 int he group of tea and coffee 29 in the group, two patients were excluded from the study because they did not consume coffee before surgery. Time of getting stool in the postoperative period after elective resection surgery on the colon and rectum is significantly shorter after drinking coffee for about 15h (p <0.01). Also, the length of hospital stay was significantly shorter after drinking coffee (p <0.01). Time of hospitalization in subjects/respondents coffee consumers on average lasted 8.6 days with consumers of tea for 16 days. The incidence of postoperative complications was significantly lower after consumption of coffee (p <0.05). CONCLUSION: Postoperative consumption of coffee is a safe and effective way to accelerate the establishment of the bowel function after colorectal resection surgery. PMID- 26843725 TI - Neurodevelopmental Follow Up After Therapeutic Hypothermia for Perinatal Asphyxia. AB - INTRODUCTION: Neuroprotective benefit of therapeutic hypothermia in term newborns with hypoxic-ischemic encephalopathy (HIE) was assessed by analyzing survival and neurodevelopmental outcome of neonates subjected to this procedure. MATERIAL AND METHODS: Newborns with gestational age > 36 weeks and < 6 hours of age with moderate to severe asphyxial encephalopathy underwent cooling protocol at a temperature of 33.5 degrees C for 72 hours and rewarming period of 6 hours. Outcome measures assessed were death and neurodevelopmental characteristics, which were compared at the different age using ASQ-3. Twenty-five children were assessed at age 3-6, 12-18 and 24-36 months. Median gestational age was 40 weeks, birth weight 3470 g, Apgar score 2/4 and pH on admission to the hospital 7.02. Four (16%) children died. RESULTS: At the first assessment developmental categories of communication were normal in 78.9%, problem solving in 63.2%, personal-social in 68.4%, gross motor in 68.4%, and fine motor in 42.1% with a high need of retesting in this area. Second assessment was done in 17 patients: developmental categories of communication normal in 58.8%, problem solving in 70.6%, personal-social in 64.7%, gross motor in 64.7%, and fine motor in 35.3%. Third evaluation was done in 14 patients: developmental categories of communication were normal in 64.3%, problem solving in 71.4%, personal-social in 57.1%, gross motor in 64.3%, and fine motor in 42.9%. CONCLUSION: There was no correlation between baseline parameters and outcome. Results of the study are showing that therapeutic hypothermia in term newborns can provide better survival and less neurologic sequels in HIE patients. PMID- 26843726 TI - Osteonecrosis of the Jaw After Bisphosphonates Treatment in Patients with Multiple Myeloma. AB - BACKGROUND: Bone lytic lesion in Multiple myeloma are the most commonly presented symptoms which require treatment with bisphosphonates (BPs). BPs are providing supportive care, reducing the rate of skeletal morbidity but evidently not abolishing it, the criteria for stopping their administration have to be different from those used for classic antineoplastic drugs, and they should not be stopped when metastatic bone disease is progressing. Osteonecrosis of the jaw (ONJ) has been associated recently with the use of BPs. AIM: The aim of these study is to evaluate the incidence of ONJ in patients with MM treated with mixed biphosphonates. PATIENTS AND METHODS: We analyzed total 296 myeloma patients (150 male and 146 female). Mostly effected age group with 58,1% is age more than 60 years up to 88 years, diagnosed in our institution in the period 2005-2015. We used intravenous or oral forms of biphosphonates such as pamidronate, ibandronate, clodronate and zolendronic acid. The patients were evaluated for ONJ. RESULTS: The incidence of ONJ in our group of patients treated with Bps was 4,6% from our group of 260 patients 87,8% received BPs therapy and patients which haven't received BPs 12,2%. From this group, 95,4% (248) didn't show ONJ, and 4,6% (12) showed ONJ. The period of this treatment with BPs is an important risk factor for development of ONJ, average duration of BPs therapy in patients which show adverse effects is 26.8+/-13.7 months, from the total number of 12 patients that developed ONJ adverse effects, we have 8 patients which received treatment with Zolendronic acid and the remaining 4 patients which were treated with other BPs combinations without Zolendronic acid. CONCLUSIONS: All patients treated for MM must continue with the therapy with Zolendronic acid and Pamidronate, each patient must be individually treated according to his response of the treatment (dose, frequency and duration of therapy). PMID- 26843727 TI - The Influence of Serum Cortisol Level Onto Perceptive Experience of Optimism in Patients with Newly Diagnosed Cancer. AB - THE AIM: The aim of this study is to investigate the correlation between the morning level of serum cortisol and perceptive experience of optimism in a selected group of 60 patients with newly diagnosed cancer who were treated at Mostar University Clinical Hospital during a one-month period. PATIENTS AND METHODS: The morning level of serum cortisol was measured in all patients following the verification of oncological disease. The patients also filled out a questionnaire of socio-demographic data, as well as the scales for optimism/pessimism assessment. RESULTS: The average morning serum cortisol level was within the reference values in the majority of patients, independently of their perceptive experience of optimism/pessimism. There was no significant difference in the morning level of serum cortisol among the subgroups of patients high and low on the scale of optimism, as well as the scale of pessimism. No correlation existed between the serum cortisol morning level and expressed optimism/pessimism, as well. The great majority of respondents had secondary and lower education, was retired or unemployed, and suffered lower socio-economic conditions of life. Therefore, their access to medical information and their knowledge of cancer modern treatment options and possibilities were restricted, what may also have an influence onto perceptive experience of optimism/pessimism. CONCLUSION: The results concerned with the perceptive experience of optimism/pessimism assessment were not a consequence of stress reaction but they were more correlated to general personal characteristics, the level of education, and socio-economic status of patients. The results do not confirm the impact of morning serum cortisol level onto physiological reactions to stressful conditions and situations in selected group of patients with de novo carcinoma. PMID- 26843728 TI - Assessment of Fatigue in End Stage Renal Disease Patients Undergoing Hemodialysis: Prevalence and Associated Factors. AB - BACKGROUND: Fatigue is a common symptom referred by many patients undergoing hemodialysis. Fatigue is associated with poor health-related quality of life (HRQoL) and is an important predictor for survival of hemodialysis patients. AIM: To assess the levels of fatigue and demographic factors affecting it among patients with End Stage Renal Disease undergoing hemodialysis. METHODS: This quantitative study was carried out in two Dialysis Units of Hospitals in Athens Region. Between January 2015 and June 2015, 129 hemodialysis patients completed the Greek Version of the Fatigue Assessment Scale (FAS). Demographic data of patients was recorded. For the statistical analysis IBM SPSS Statistics version 20 was used. RESULTS: The mean FAS score was 24.99. 49 patients (38.0%) were non fatigued, 61 patients (47.3%) were fatigued, and 19 patients (13.7%) were extremely fatigued. Higher levels of fatigue were reported among hemodialysis patients residing in urban areas, in those with low educational level and unemployed. CONCLUSION: The findings of this study can be used in the assessment of fatigue and early identification of high-risk patients (especially of the unemployed, those who occupy with domestic works, those with low educational level and of urban citizens). Use of this knowledge by hemodialysis nurses may lead to a better understanding of the factors of fatigue in ESRD, which in turn may lead to a more effective treatment. PMID- 26843729 TI - Does Early Post-operative Administration of Aspirin Influence the Risk of Bleeding After Coronary Artery Bypass Graft Surgery? A Prospective Observational Study. AB - BACKGROUND: Aspirin has a proven role in preventing thrombotic diseases. However, given its anti-platelet activity, it is often assumed that its early post operative administration significantly increase the amount of post-operative bleeding. AIM: The aim of this study was to determine whether early post operative administration of aspirin influence the risk of bleeding in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: In a prospective observational study, 100 consecutive patients undergoing first time elective CABG surgery were include in the study. Patients received a low dose of aspirin (75 150 mg per day) either 1 hours (the early aspirin group; n=43) or 6 hours after surgery (the late aspirin group; n=57). Total mediastinal blood drainage, blood drainage after 6 hours, incidences of re-operation for the control of bleeding and transfusion of red blood cells (RBCs) and blood products were recorded and followed until chest tube removal. RESULTS: The groups were found to be matched for the confounding variables and no significant differences were found between post-aspirin bleeding (p=0.37), RBCs and blood product usage (p=0.90) or incidences of re-operation for control of bleeding (p=1.00) between the two groups. CONCLUSIONS: Early administration (1 hour after surgery) of aspirin did not appear to increase the risk of post-operative bleeding in patients undergoing CABG. Thereby, its early administration in such cases may be considered. Although further well-designed randomized controlled trials to confirm the safety and efficacy of early administration of aspirin after CABG surgery are warranted. PMID- 26843730 TI - Can Subcision with the Cannula be an Acceptable Alternative Method in Treatment of Acne Scars? AB - BACKGROUND AND OBJECTIVES: Most people who experience the acne suffer from damage under the surface of their skin which causes saucer-like depressions or pits on their skin. Sometimes the skin loses its underlying support and develops fibrous bands of tissue between the skin and subcutaneous layer, which pull on the epidermis and cause a wavy texture called as rolling scar. Treatment of acne scars is a therapeutic challenge that may require multiple modalities. Subcision is a procedure that has been reported as a beneficial method in the treatment of rolling acne scars. Although Subcision is a valuable method, its efficacy is mild to moderate because of the high recurrence rate and patients dissatisfaction due to some side effects include post procedure inflammation. MATERIALS AND METHODS: This pilot study is a clinical trial. The 8 patients suffered from mild to severe rolling acne scars on their face with symmetrical distribution of lesions, underwent Subcision with the Cannula No 18 and 21 and followed-up for 3 months. Outcomes of Subcision procedures were assessed by 3 board certified dermatologists (blind) after 2 session of treatment. The patients' satisfaction was considered to compare with dermatologist's opinions. The degree of improvement and satisfaction of the treatment estimated with these points: poor: 0, fine: 1-3, good: 4-6, and very good: 7-9. The data were finally analyzed with SPSS-18 software. RESULTS: Subcision with the Cannula showed good and very good improvement in about 88% of patient with a satisfaction good and very good improvement in all of patients (100%). Assessment of photographic data showed 100% improvement in scar depth, topography and overall appearance of acne scars. The average numbers of lesions before the treatment were 24.8 +/- 12.1 and after treatment it was reduced to 12.8 +/- 2.1 (p<0.05). CONCLUSION: Subcision with the Cannula appears to be a safe method with high efficacy in the treatment and high satisfaction in patients as we observed an interesting cure rate (more than 50% after 2 sessions). It demonstrates to be a safe procedure because it performed by single perforation in each side instead of multiple perforations that helps to reduce the patients' pain and risk of scars. In other hand Cannula-based Subcision needs considerable fewer sessions of surgery and also less recovery time. PMID- 26843731 TI - The Effect of Hysterectomy on Women's Sexual Function: a Narrative Review. AB - BACKGROUND: Regarding the contradictions about positive and negative effects of hysterectomy on women's sexual functioning, this study was conducted to review the studies on the effect of hysterectomy on postoperative women's sexual function. METHOD: This study was a narrative review and performed in 5 steps: a) Determining the research questions, b) Search methods for identification of relevant studies, c) Choosing the studies, d) Classifying, sorting out, and summarizing the data, and e) reporting the results. FINDINGS: The review of the studies yielded 5 main categories of results as follows: The effect of hysterectomy on Sexual desire, the effect of hysterectomy on sexual arousal, the effect of hysterectomy on orgasm, the effect of hysterectomy on dyspareunia, and the effect of hysterectomy on sexual satisfaction. CONCLUSION: According to the studies reviewed in this study, most of the sexual disorders improve after hysterectomy for uterine benign diseases, and most of the patients who were sexually active before the surgery experienced the same or better sexual functioning after the surgery. An important solution for making these women ready to face with postoperative sexual complications is to train them on the basis of needs assessment in order that the patients undergoing hysterectomy be ready and capable of coping with the complications, and their sexual functioning improves after the surgery. PMID- 26843732 TI - The Effect of Nasal Packing Removal on Patients Anxiety. AB - AIM: We aimed to investigate the effect of removal of merocel nasal packings on patients anxiety after septoplasty using Hamilton Anxiety Scale. MATERIAL AND METHODS: Total amount of 50 patients who had septoplasty operation in the Department of Ear, Nose and Throat Clinic of our hospital were enrolled to the study. Patients anxiety determined using Hamilton Anxiety Scale. The patients anxiety levels were measured before 24 hours before the operation (Group 1), 48 hours after operation before nasal packing removal (Group 2) and 60 minutes after nasal packing removal (Group 3). RESULTS: Patients were evaluated according to the Hamilton Anxiety Scale; in Group 1 15.3 +/- 7.2, 19.3 +/- 7 in Group 2, 14.6 +/- 6,5 in Group 3 was measured. CONCLUSION: There was no statistically significant difference between Groups 1 and 3. There is a statistically significant difference on patients anxiety levels 48 hours after operation before nasal packing removal (p<0.001). There is an statistically significant increase of patients anxiety before packing removal. We recommend using soluble packings or sewing techniques without nasal packings after septoplasty because of patient comfort after operation. PMID- 26843733 TI - Differences Among Body Mass Index (BMI) Groups in Patients Undergoing First Elective Percutaneous Coronary Intervention. AB - BACKGROUND AND PURPOSE: Body Mass Index (BMI) is known to be an independent risk factor for hypertension, type 2 diabetes mellitus, dyslipidemia and various cardiovascular diseases. Our aim was to investigate the differences among BMI groups in patients undergoing first elective PCI. METHODS: 781 consecutive patients who underwent their first-time elective PCI from September 2011 to December 2013 in the Department of Cardiology were enrolled in the study. The patients with BMI < 18.5 kg/m(2) or > 50 kg/m(2) and those who had previously undergone revascularization were excluded from the study. Patients were categorized according to their BMI groups. BMI 18.5 - 24.9 kg/m(2) normal group, 25 - 29.9 kg/m(2) overweight group and > 30 kg/m(2) obese group. We studied the demographic, angiographic, and interventional differences between BMI groups. RESULTS: Compared with normal weight individuals, those obese were younger (61.9 +/-10.34 vs. 58.41 +/- 8.01 p = 0.0006), had higher prevalence of diabetes mellitus (46.4% vs. 26.6% p = 0.0001), dyslipidemia (77.5% vs. 65.4% p=0.0134) and hypertension (1.3% vs. 81.3% p=0.0067). There was a greater use of calcium channel blockers (CCBs) and Angiotensin Enzyme Inhibitors (ACEIs)/Angiotensin Receptor Blockers (ARBs) in obese individuals but it was not statistically significant. Obese individuals were associated with higher risk anatomy (3-Vessel CAD or LM) compared to normal individuals but not statistically significant (18.8% vs. 14.2% p=0.25). Obese patients were associated with a higher length of stents/person used (36.7 +/- 22.02 vs. 31.7 +/- 17.48 p=0.016) and also a larger diameter of stents/person used (3.14 +/- 0.4 vs. 2.98 +/- 0.33 p=0.0001) compared to normal individuals. CONCLUSIONS: Patients with a higher BMI are younger and have diabetes mellitus, hypertension and dyslipidemia more frequently. Patients with a higher BMI have a higher length and larger diameter of stents/person used, probably related to a more extensive coronary artery disease. PMID- 26843734 TI - Early Clinical Outcome of Acute Poisoning Cases Treated in Intensive Care Unit. AB - INTRODUCTION: A variety of factors have influenced the significant incidence of morbidity and mortality of acute poisoning and the timely recognition and properly management of critically ill poisoned patients is a key component. The aim of this study is to reveal the reasons for ICU admission of acutely poisoned patients, the main factors influencing the course and outcome of patients in relation with clinical approaches applied, available resources and infrastructure of treatment. MATERIALS AND METHODS: This is a retrospective study based on most reachable variables extracted from patients' medical records and ED registers of patients admitted at the medical ICU of "Mother Teresa" University Hospital in Tirana over two (2012-2013) years. Demography, time of exposure, etiology and circumstances of poisonings, assessment and treatment, reasons for ICU admission, course and outcome were duly obtained. RESULTS: The number of ICU treated patients was 118, consisting in 47.4% (56) males and 52.5% (62) females which represented 10.2% of poisoned patients admitted during this two-year-period in ED and 9.2% of other etiology ICU admitted patients. Mean was 42.6 years for males, and 38 years for females. About 55.9% were urban residents and 44% rural ones. The elapsed time from toxic exposure to treatment initiation had varied between 2 6 hours, 44% arrived in the hospital <4 hours. The toxic exposures were intentional in 87.2% of cases, with a male:female ratio was 0.8:1. Agrochemicals such as Aluminum phosphide and organophosphates were involved in 77.1% of cases. Cardiovascular collapse and respiratory failure were the main clinical syndromes encountered. Mechanical ventilation was required in 31.4% of patients. The length of ICU stay was 2.73 (0.96) days and the mortality was 54.2%. CONCLUSION: This study evidenced that highly lethal toxicants used in poisoning acts such as agrochemicals, high rate of suicide, notwithstanding the infrastructure and resources available employed for ICU patients' treatment, all had played a role in the very high rate of mortality in this cluster of patients. PMID- 26843735 TI - Evaluation of the Etiologies of Implant Fracture in Patients With Fractures of the Implants of Lower Limbs' Long Bones. AB - BACKGROUND: Orthopedics implants are important tools for treatment of bone fractures. Despite available recommendations for designing and making the implants, there are multiple cases of fracture of these implants in the body. Hence, in this study the frequency of failure of implants in long bones of lower extremities was evaluated. METHODS AND MATERIALS: In this cross-sectional study, two types of fractured implants in the body were analyzed and underwent metalogical, mechanical, and modeling and stress-bending analysis. RESULTS: The results revealed that the main cause of fractures was decreased mechanical resistance due to inappropriate chemical composition (especially decreased percentages of Nickel and Molybdenum). CONCLUSIONS: It may be concluded that following the standard chemical composition and use of optimal making method are the most important works for prevention of failure of implants. PMID- 26843736 TI - Risk Factors for Retinopathy of Prematurity in Premature Born Children. AB - INTRODUCTION: Retinopathy of Prematurity (ROP) represent disease of the eye in premature born children which affects immature blood vessels of the retina during their development. The emergence of retinopathy of prematurity depends on the interaction of multiple factors, such as: gestational age, low birth weight, hypoxia, duration of oxygen supplementation, respiratory distress syndrome, twin pregnancy, anemia, blood transfusions, sepsis, intraventricular hemorrhage, hypotension, hypothermia, etc. If remain unrecognized and untreated it can cause severe visual impairment and blindness in children, but can also be prevented with timely screening. GOALS: To establish the number of patients with development of retinopathy of prematurity active forms in the observed time period and examine which risk factors have most significant impact on its origin. MATERIAL AND METHODS: In a clinical, retrospective study we observed a total of 80 premature born children in the period from January to May 2015 with regard to listed risk factors identified for eye examination. RESULTS: From a total of 80 premature newborns sample included 48.8% male and 51.2% female children. The active form of ROP developed in 6.2% of cases, while in 93.8% of cases there was a spontaneous resolution. Patients who developed active form of ROP have significantly younger gestational age (26.4+/-1.5 weeks) and lower birth weight (874+/-181 grams), lower Apgar score in the first and fifth minute and were longer on oxygen therapy (20+/-3.4 days). CONCLUSION: Of the potential risk factors that could affect the development of ROP active form following factors have a statistically significant influence: early gestational age, low birth weight, lower Apgar score and prolonged oxygen therapy (p <0.05). PMID- 26843737 TI - Exfoliative Skin-peeling, Benefits from This Procedure and Our Experience. AB - The peeling procedure is a valuable method for the aged skin, photo aging, acne scars and melasma. It should be performed by dermatologist. Pre peeling preparation of the skin is very important to prepare the skin for this procedure. It can be archived by applying the mask with acids twice a week. The caring of the skin after procedure is also very important for the success of the treatment. Same cases may have complication but managing them is also a challenge for dermatologist. PMID- 26843738 TI - Genetic Profile of Patients with Familial Mediterranean Fever (FMF): Single Center Experience at King Hussein Medical Center (KHMC). AB - OBJECTIVE: To describe the spectrum of genetic mutations in patients with clinical diagnosis of Familial Mediterranean Fever. METHOD: This is a retrospective study of 3359 sera samples for patient with clinical diagnosis of FMF, over a period of 6 years. The samples were tested for 12 mutations of the MEFV gene by PCR& hybridization of the PCR product with Probes immobilized as an array of panel lines. RESULTS: A total of 1868 (55.6%) samples were found negative, and one or more mutations were detected in 1491 (44.4%) distributed along the mutations. Of the positive results, the Frequency of the mutations was as follows, the M694V was the most common mutation 30%, followed by E 148Q 21.5%, V 726 A 20%, M6801 G/C 9%, M6941 8.3%, P369s 3.7%, A744S 3.1% and 4.2% among the 4 remaining mutations. CONCLUSION: Frequency of common mutations in our study show similar results in comparisons with Mediterranean countries like Egypt, Turkey, and Syria with the most common mutation in our study being M694V followed by E148 Q. PMID- 26843739 TI - A Clinical Sign in Pediatric Sclerosis, Farhad's Sign. AB - The scleroderma group of diseases is characterized by the presence of hard skin. The pathogenesis of scleroderma include excessive production of collagen and extracellular matrix by fibroblasts, not only in the skin but also in vital organs and around blood vessels with endothelial cell injury. Systemic Sclerosis (SSc) usually constitutes less than 1% of most pediatric rheumatology clinic populations. Females are affected much more commonly than males. PMID- 26843740 TI - Anomalous Origin of Left Circumflex Artery. AB - INTRODUCTION: The coronary anatomic variation of the left circumflex artery (LCx) is considered as the most common anatomic variation with a separate ostium from the right sinus, and very unusual variation as a proximal branch of right coronary artery (RCA). CASE REPORT: We report two cases, the first case is a 64 year-old man with chest pain and with history of hypertension, obesity, dyslipidemia and current smoker, and the second case is a 67-year-old who presented to the emergency department with chest pain and with a past medical history of arterial hypertension and type 2 diabetes mellitus. In the coronarography of the first case is detected an ectopic left circumflex coronary artery from the right coronary sinus with stenotic changes in RCA and LCx. The second case in the coronary angiography revealed an ectopic left circumflex coronary artery from the proximal part of the right coronary artery with stenotic changes in LAD, RCA and LCx. Based on guidelines for revascularization our patients successfully underwent treatment procedures. We present two cases that because of the atherosclerotic coronary artery disease leads to the need of coronarography find out the presence of coronary artery anomalies. CONCLUSION: During the coronarography we should think about coronary artery anomaly or missing artery knowing that type of these anomalies, considering that may be a contributing factor in the development of the atherosclerosis determines the method of the treatment. PMID- 26843742 TI - Evaluation of flexural strength of resin interim restorations impregnated with various types of silane treated and untreated glass fibres. AB - BACKGROUND: Flexural strength is an important mechanical property that determines the long-term prognosis of interim restorations. Studies are lacking regarding the effect of silanation of the various types of glass fibre impregnation on the flexural strength of resin interim restorations. METHODS: A customized metal die was milled to simulate the prepared abutments of a three-unit fixed dental prosthesis. A total of seventy five samples of interim fixed dental prostheses were prepared using autopolymerizing tooth colour acrylic resin. Unidirectional and woven forms of glass fibres (Stick and Stick Net), which were silane treated and untreated were used to reinforce the resin matrix. Fifteen samples were prepared for each group along with unreinforced group serving as control. The flexural strength was evaluated with universal testing machine. RESULTS: The means and standard deviations of flexural strength for different groups were 13.90 +/- 2.96 (control), 61.58 +/- 5.26 (unidirectional fibres), 30.89 +/- 3.60 (woven fibres), 112.05 +/- 5.51 (silane treated unidirectional fibres) and 73.85 +/- 4.10 (silane treated woven fibres) respectively. The mean flexural strength of silane treated unidirectional fibres (112.05 MPa) was highest and statistically highly significant (P < 0.0001) compared to all other groups. CONCLUSIONS: Within the limitations of the current study, flexural strength of the reinforced PMMA interim fixed dental prosthesis was significantly higher (P < 0.0001) when compared to the unreinforced PMMA interim fixed dental prosthesis. The use of silane treated unidirectional glass fibres is an effective method of reinforcing interim fixed restorations made of PMMA resins. PMID- 26843741 TI - Short-gap Isolated Esophageal Atresia Causing Stridor Due to Compression of the Trachea. AB - Isolated esophageal atresias are reported always to be associated with long gap in the literature. In this manuscript, we aimed to discuss the imaging and surgical treatment methods of an isolated esophageal atresia case with 'short gap' who had stridor due to compression of the trachea by dilated upper esophageal pouch and had not identified previously in the literature. PMID- 26843743 TI - Evaluation of the effect of surface preparation using phosphoric acid and luting cement on the flexural strength of porcelain laminate veneering material. AB - BACKGROUND: Conventionally HF acid has been used for etching ceramic veneer restorations before their cementation. Studies are lacking regarding the effectiveness of phosphoric acid as a substitute for HF acid for etching the ceramic veneers. The purpose of this study was to evaluate the effectiveness of surface preparation of porcelain laminate veneers using phosphoric acid, as compared to HF acid etching in providing the necessary surface roughness conducive to development of an effective bond between the ceramic laminate and the resin luting cement. METHODS: 210 porcelain discs of 15 mm diameter and 0.9 mm thickness were prepared. These study samples were divided into seven groups of thirty samples each. Surfaces of the first (control) and the second group of samples were not prepared. The surfaces of other five groups were prepared with different surface treatments. Further all the groups of specimens were coated with a layer of resin luting cement. Flexural strength of each specimen was determined using universal testing machine and the results were compared. RESULTS: The combination surface treatment using alumina surface abrasion followed by etching with phosphoric acid provided the highest flexural strength with the mean flexural strength of 101.11 MPa, followed by alumina surface abrasion (95.41 MPa), and phosphoric acid surface etching (81.68 MPa). CONCLUSION: Laminate veneers surface treated using 50 MUm alumina abrasion followed by etching with phosphoric acid showed the highest flexural strengths after resin coating compared to other groups. PMID- 26843744 TI - Comparative clinical evaluation of removable partial dentures made of two different materials in Kennedy Applegate class II partially edentulous situation. AB - BACKGROUND: Cast Chromium Cobalt alloy has been the material of choice for fabricating Removable Partial Dentures (RPDs) but has certain drawbacks. Newer materials like the flexible Nylon based Super Polyamide have been introduced to overcome these drawbacks. The present study has compared the above two materials for nine clinical parameters. METHOD: The study was carried out on 30 patients presenting with a Kennedy Applegate class II partially edentulous situation who were divided into two equal groups and clinically assessed. RESULT: Statistically significant results were obtained in favor of flexible RPDs, in the parameters of 'aesthetics' and 'overall patient satisfaction'. Both groups showed more or less similar values for 'frequency of fracture of the prosthesis during usage' with the incidence being slightly higher for patients wearing the cast RPDs. The clinical parameters of 'oral soft tissue tolerance', 'gingival health', 'periodontal health' and 'adaptability in areas with undercut' were statistically at par for all the 30 patients thus suggesting the comparable biocompatibility of the two materials. The highlight of this study was the relative ease in fabrication of the flexible RPDs as compared to the cast RPDs. CONCLUSION: Based on the favorable clinical results of this study, it can be summarized that the flexible RPDs is a viable alternative to cast RPDs in Kennedy Applegate class II partially edentulous situation in the short term. PMID- 26843745 TI - Intrapulpal thermal changes during direct provisionalization using various autopolymerizing resins: Ex-vivo study. AB - BACKGROUND: Resin materials used in the fabrication of direct provisional restoration exhibit an exothermic reaction and the extent of damage may also depend on the remaining dentine thickness. An ex-vivo study was envisaged to compare the time related temperature changes in the pulp chamber during the fabrication of fixed partial denture provisional restorations using direct technique. The effect of differently prepared teeth (with varying remaining dentine thickness) on the above mentioned temperature changes were also evaluated. METHODS: Thermal changes were calculated in pulp chamber of three differently prepared tooth having different amount of remaining dentinal thickness (45 samples) and control with no tooth media (15 samples), using three different types of autopolymerizing provisional restorative materials using Cr/Al thermocouple connected to digital thermometer. RESULTS: The data for the mean peak temperature rise was subjected to one way ANOVA analysis for relative comparison among subgroups within each main group and across the main groups. The results showed a statistically significant difference across both the subgroups and the main groups (p < 0.001). Then Turkey HSD test was applied to determine the significance of statistical difference between the means, within the groups. The differences in temperature rise were statistically significant for the three resins (p < 0.001). CONCLUSION: Polymethylmethacrylate (DPI) showed the highest temperature rise value followed by polyethyl methacrylate (Tempron) and Bis acrylate composite (CoolTemp). The maximum temperature rise was found on molar full veneer preparation followed by molar three quarter preparation and premolar three quarter preparation. Data and results from current study may assist clinicians to select an autopolymerizing provisional restorative resin when employing direct technique of fabricating provisional restorations for a specific tooth preparation which would cause minimal thermal trauma to pulpal tissue. PMID- 26843746 TI - Dimensional accuracy of two rubber base impression materials as a function of spacer design and techniques in custom trays for fixed partial dentures. AB - BACKGROUND: A prostheses can't be better than the cast over which it has been fabricated. To make accurate casts, accurate impressions are mandatory. To get an accurate and dimensionally stable impression, various techniques and materials have been advocated. This study compares the most commonly used techniques and materials for dimensional accuracy. Two types of spacers were designed to compare the addition silicon and polyether and their techniques. METHODS: A metal die was used to make the impressions. A total of 60 impressions were made using multiple mix and monophasic techniques for addition silicon and polyether in custom trays. A travelling microscope was used to measure the dimensional accuracy of die stone casts retrieved from impressions. RESULTS: The results were compared using paired t test and SPSS software. The study was highly significant (p < 0.001). The polyether was more accurate than the addition silicon and spacer design I (adapted to the edentulous area) was more accurate than the design II (spacer over the abutments, not adapted to edentulous area). The multiple mix technique was more accurate than the monophasic for addition silicon. CONCLUSION: The combination of multiple mix technique with spacer design I for addition silicon gave the best accurate results. PMID- 26843747 TI - Evaluation of dental implant insertion torque using a manual ratchet. AB - BACKGROUND: Dental implant insertion torque is crucial for the success of the implant and the prosthesis. This in-vivo study was undertaken to determine the average insertion torque being applied to the dental implant while surgically placing it with a non-calibrated manual ratchet. METHODS: Three dental surgeons placed a total of 45 dental implants (Touareg, ADIN, Afula, Israel) in 42 selected patients. Each surgeon placed 15 implants. Standardised protocols were followed to prepare the site to place the dental implant. Each implant was placed using a manual non-calibrated implant ratchet first. Once the implant was nearly placed, a manual calibrated torque gauge ratchet was used to place the implant in its final position and at that instance, the maximum final torque applied was noted on the torque gauge scale. RESULTS: The mean dental implant insertion torque applied by three surgeons using a non-calibrated manual ratchet was estimated to be 63.26 Ncm with a standard error of 6.80 i.e. (63.26 + 6.8), which was significantly higher than the baseline of 35 Ncm (p < 0.0001). The mean dental implant torque applied by Surgeon 1, 2 and 3, respectively, was 65.93 Ncm, 62.60 Ncm and 62.13 Ncm and this difference amongst them was found to be statistically insignificant (p > 0.05) and each of them had reached more than the baseline level of 35 Ncm individually and significantly (p < 0.0001). CONCLUSION: Without the use of torque measuring devices, an average surgeon may achieve an average insertion torque of 63.26 + 6.8 Ncm. PMID- 26843748 TI - Comparative study of immediate functional loading and immediate non-functional loading of monocortical implants. AB - BACKGROUND: Attempts to shorten the overall length of treatment have focused on immediate loading, subsequent to implant placement. Prosthetic rehabilitation immediately after implant placement can be either functional or non-functional in nature. There is paucity of literature on the comparative evaluation of immediate functional and immediate non-functional loading of implants. This in-vivo study was undertaken to comparatively evaluate Immediate Functional Loading and Immediate Non-Functional Loading of monocortical implants with a follow-up period of 18 months. METHODS: 50 partially edentulous cases were selected for the study. The cases were divided into two groups. In first group (Group-1), 25 implants were subjected to immediate functional loading. In second group (Group-2), 25 implants were subjected to immediate non-functional loading. The crestal bone loss, clinical stability and degree of osseointegration of these two groups were comparatively evaluated. RESULTS: The crestal bone loss in both groups was within acceptable limits. The implant stability, which is a reflection of the status of bone-to-implant interface, was comparable in both the groups at different time intervals. Although, the ISQ values in Group-2 were slightly higher than those in Group-1, the results were not statistically significant. Radiodensity indicating degree of osseointegration at different time intervals in both groups was also comparable. CONCLUSION: Both the IFL and INFL protocols can be undertaken satisfactorily in rehabilitation using endosseous implants; however, the main factors for success in IFL and INFL are case selection, meticulous treatment planning and the precision of technique. PMID- 26843749 TI - Surface characterization of nickel titanium orthodontic arch wires. AB - BACKGROUND: Surface roughness of nickel titanium orthodontic arch wires poses several clinical challenges. Surface modification with aesthetic/metallic/non metallic materials is therefore a recent innovation, with clinical efficacy yet to be comprehensively evaluated. METHODS: One conventional and five types of surface modified nickel titanium arch wires were surface characterized with scanning electron microscopy, energy dispersive analysis, Raman spectroscopy, Atomic force microscopy and 3D profilometry. Root mean square roughness values were analyzed by one way analysis of variance and post hoc Duncan's multiple range tests. RESULTS: Study groups demonstrated considerable reduction in roughness values from conventional in a material specific pattern: Group I; conventional (578.56 nm) > Group V; Teflon (365.33 nm) > Group III; nitride (301.51 nm) > Group VI (i); rhodium (290.64 nm) > Group VI (ii); silver (252.22 nm) > Group IV; titanium (229.51 nm) > Group II; resin (158.60 nm). It also showed the defects with aesthetic (resin/Teflon) and nitride surfaces and smooth topography achieved with metals; titanium/silver/rhodium. CONCLUSIONS: Resin, Teflon, titanium, silver, rhodium and nitrides were effective in decreasing surface roughness of nickel titanium arch wires albeit; certain flaws. Findings have clinical implications, considering their potential in lessening biofilm adhesion, reducing friction, improving corrosion resistance and preventing nickel leach and allergic reactions. PMID- 26843750 TI - Evaluation of the hard and soft tissue changes after maxillary advancement with rigid external distractor in unilateral cleft lip and palate induced maxillary hypoplasia. AB - BACKGROUND: Midfacial growth retardation in cleft lip and palate (CLP) cases, is seen in all the three dimensions. Conventionally these cases are managed by orthographic surgery which has a high rate of relapse. The application of the distraction osteogenesis (DO) has revolutionized the management protocol. The aim of the study was to evaluate the efficacy of rigid external distractor (RED) in management of cleft induced maxillary hypoplasia. METHODS: Ten cases of unilateral CLP between 11 and 20 years of age having gross midfacial deficiency and those who have undergone presurgical orthodontic treatment were included in the study. The cases were operated for Le Fort 1 osteotomy and application of RED. DO was carried out through transnasal traction wires. Clinico-radiological evaluation of presurgical and 1, 6 and 12 months post distraction parameters were statistically analysed by application of paired 't'-test. RESULT: There were 4 males and 6 females with a mean age of 15.1 years. The mean distraction carried out was 14.95 mm. There was a significant improvement in all the hard and soft tissue parameters except SNB. Facial profile improvement and stable occlusion was achieved in all the cases. CONCLUSION: Midfacial DO using RED is a versatile procedure where the maxilla can be moved in multiple planes to achieve a functional, aesthetic and occlusal balance. Keeping in view of the significant relapse rate the clinicians are required to plan 15-20% excess amount of distraction. PMID- 26843751 TI - Comparative evaluation of anchorage loss between self-ligating appliance and Conventional pre-adjusted edgewise appliance using sliding mechanics - A retrospective study. AB - BACKGROUND: Although a number of studies have been undertaken to evaluate the friction characteristics of self-ligating brackets, there have been only few studies which have actually evaluated the clinical efficiency of these self ligating brackets. This study was done to evaluate the clinical efficiency of Passive SLB (Smart Clip) in terms of anchorage loss and total treatment duration by comparing it with a Conventional pre-adjusted edgewise (M.B.T.) bracket system. METHODS: This was a retrospective study in which the study sample comprised of ten patients treated with Passive SLB (Smart Clip, 0.022") and ten patients treated with Conventional pre-adjusted edgewise (M.B.T.) bracket system (0.022") who required therapeutic extraction of U/L first premolars as a part of their orthodontic treatment plan. Pretreatment and post treatment lateral cephalograms were taken to evaluate the amount of anchorage loss. The total time required to complete the treatment was also recorded. RESULTS: Anchorage loss observed with Passive SLB (Smart Clip) sagittally was 1.90 +/- 0.68 mm in the maxilla and 1.90 +/- 0.43 mm in the mandible and vertically was 0.52 +/- 0.53 mm in the maxilla and 0.70 +/- 0.69 mm in the mandible. Anchorage loss observed with Conventional pre-adjusted edgewise (M.B.T.) bracket system sagittally was 2.08 +/ 0.43 mm in the maxilla and 1.95 +/- 0.44 mm in the mandible and vertically was 0.50 +/- 0.49 mm in the maxilla and 0.68 +/- 0.53 mm in the mandible. The average time taken for the completion of treatment in Passive SLB (Smart Clip) and Conventional pre-adjusted edgewise (M.B.T.) bracket system was 14.0 +/- 2.4 and 17.2 +/- 2.6 months respectively. CONCLUSION: There was no statistically significant difference in the quantum of anchor loss between Smart Clip self ligating bracket system and Conventional pre-adjusted edgewise (M.B.T.) bracket system although Smart Clip self-ligating bracket system is efficient in reducing the overall treatment time. PMID- 26843753 TI - Determination of mesiodistal width of maxillary anterior teeth using inner canthal distance. AB - BACKGROUND: Selection of appropriately sized maxillary anterior teeth is one of the important aspects of complete denture prosthodontics. In the past several methods have been proposed, but little consensus on an effective method for anterior teeth selection has been reached. Inner canthal distance is one of the reliable anatomic dimension that may provide a valid approach to anterior teeth selection. This study was aimed to ascertain the co-relation between inner canthal distance (ICD) and combined mesiodistal width of maxillary anterior teeth. METHOD: This study was conducted in Army Dental Centre (R & R) Delhi Cantonment between Aug 2006 to Mar 2008. Eight hundred dentate Indian subjects of four different ethnic group; Such as Rajputs, Marathas, Sikh and Tamilian. 100 males and 100 females from each race under the age group of 18-30 years formed the subjects of study. The ICD and mesio-distal width of maxillary anteriors were measured using Digital Vernier Caliper. The Data obtained was statistically analyzed. RESULTS: A consistent ratio of 1.61 was found between ICD and combined mesiodistal width of maxillary anteriors in all four ethnic group. The mean value showed no statistically significant difference between sex. The variation in the ratio between the ethnic groups was negligible. CONCLUSION: The findings of the study indicated that, to select the combined mesiodistal width of maxillary anterior teeth, ICD of the required patient should be multiplied by 1.61. This ratio was consistent with all the four ethnic groups irrespective of sex. PMID- 26843752 TI - Pharyngeal airway analysis in obese and non-obese patients with obstructive sleep apnea syndrome. AB - BACKGROUND: Sleep disorders are a group of disorders characterized by abnormalities of respiration during sleep. OSA (Obstructive Sleep Apnea) is characterized by the repetitive episodes of complete or partial collapse of the upper airway during sleep, causing a cessation or a significant reduction of airflow. METHOD: The study population consisted of 30 control patients (AHI <= 5) events per hour, 74 patients with OSAS, including 34 Obese (BMI >= 27) and 40 non obese (BMI <= 27). Polysomnography and measurements of 21 cephalometric variables were carried out for all patients with OSAS. RESULTS: Obese patient with OSAS showed significant difference in following cephalometric parameters: (1) PAS (2) MPT (3) MPH (4) PNS-P (5) SAS. In addition, obese patient had longer tongue (TGL), more anteriorly displaced hyoid bones (H-VL) and more anterior displacement of mandible (G-VL) when compared with control groups. The findings of non-obese patients when compared to controls showed all the findings of obese patients and in addition to that narrow bony oropharynx were significant. Step wise regression analysis showed the significant predictors for all patients were MPH, PNS-P, bony nasopharynx (PNSBa), MPT, and palatal length (ANS-PNS) for AHI. The significant predictors for obese OSA (obstructive sleep apnea) group were MAS while for non-obese OSA group ANS-PNS was significant predictor for AHI (apnea hypopnea index). CONCLUSION: Craniofacial landmarks such as increase in hyoid distance, longer tongue and soft palate with increased thickness and narrowing of superior pharyngeal, oropharyngeal and hypopharyngeal airway space may be important risk factors for development of OSAS. PMID- 26843754 TI - Comparison of articulating paper markings and T Scan III recordings to evaluate occlusal force in normal and rehabilitated maxillofacial trauma patients. AB - BACKGROUND: Prosthodontic Rehabilitation of Treated Maxillofacial Trauma Cases by Evaluating Occlusal Force Distribution Using Computerized Occlusal Analysis. METHOD: 30 patients were selected for the study. 15 normal and 15 treated trauma patients were subjected to T Scan analysis and evaluated for the occlusal force distribution. RESULTS: The results take into consideration the two parameters. Firstly the largest articulating paper mark (photographed) and secondly the T scan of the same patient. Comparison was made between the largest articulating paper mark and highest force tooth in the quadrant using T Scan. The matches and no matches were then tabulated for statistical analysis assessing the frequency of the matches to the no matches. CONCLUSION: The ultimate advantage of a T Scan III analysis is that it can detect the amount of force as well as location of the highest intensity contacts of a single tooth which is very specific. PMID- 26843755 TI - Dermoid cysts of maxillofacial region. AB - The dermoid cyst is an uncommon clinicopathological lesion of developmental origin. The term dermoid cyst is used to describe 3 cysts that are closely related histologically: dermoid cyst, epidermoid cyst, and teratoma. Epidermoid and dermoid cysts are benign nature, which may occur anywhere in the body, but most predominantly in the ovary and scrotal regions. Only about 7% are found in the head and neck. The occurrence of such cysts in the oral cavity is extremely rare, with approximately 1.6% located in this area. The floor of the mouth is one of the most commonly affected area, however, these cysts can also be found in the tongue, lips, buccal mucosa and jaw bones. There is always a difficulty of making a correct diagnosis of these lesions with clinical examinations and conventional radiography. To achieve a diagnosis and to develop correct surgical strategy specialized imaging examinations such as ultrasonography (US), computed tomography (CT), Magnetic Resonance Imaging (MRI) and histopathological examination should be carried out. Treatment comprises total surgical excision the approach remains dictated logically by the cyst's location. Ample understanding and vigilance about this slow growing painless mass is essential not only because of the symptoms it produces but also due to its malignant potential. When dermoid cysts occur on the floor of the mouth, they may enlarge to such an extent that they can interfere with deglutition and produce respiratory obstruction. Early diagnosis and treatment are essential for these cystic entities. PMID- 26843757 TI - Self ligating lingual appliance. AB - Adult demand for orthodontics has grown considerably over the past 10 years propelling increased demand for Esthetic Orthodontics. Lingual appliances are a viable option toward providing Esthetic Orthodontics. The lingual surface of the teeth has a unique morphology that makes it difficult to place brackets in ideal positions. Indirect bonding has become the established methods of overcoming these discrepancies, along with the latest designs of self ligating brackets which offer more efficient mechanics and shorter treatment time. PMID- 26843756 TI - Obstructive sleep apnea (OSA): A prosthodontic perspective. AB - The subject of sleep medicine, for dental profession in general and prosthodontists in particular, continue to offer great challenges and opportunities in terms of diagnosis, treatment planning and treatment based on qualitative evidence. Although the role played by the prosthodontists is still in its infancy, there is much to learn and understand in the rapidly evolving field of sleep medicine as the recognition of co-managing patients with sleep disorders by the prosthodontists is fast becoming a reality. This article discusses at length the prosthodontic perspectives of the research in the field of sleep medicine, particularly on obstructive sleep apnea. PMID- 26843758 TI - Stabilisation of cleft maxilla using modified technique during bi-jaw orthognathic surgical procedures with simultaneous use of two stage surgical splints. PMID- 26843759 TI - Non surgical repair of iatrogenic furcal perforation of radix entomolaris. PMID- 26843760 TI - Full mouth rehabilitation of a case of rampant caries using a twin-stage procedure. PMID- 26843761 TI - Megaloblastic anemia in a teenage patient. PMID- 26843762 TI - Prosthodontic rehabilitation protocols for immediate implants. PMID- 26843763 TI - Managing prosthetic complication in implant-retained overdenture. PMID- 26843764 TI - A rare constellation of imaging findings in Wolman disease. PMID- 26843765 TI - Customizing the palatal contour of a complete denture using a Palatogram in a case of partial glossectomy. PMID- 26843766 TI - Rarest muscular imbalance, neutral zone shift and facial asymmetry. PMID- 26843767 TI - Single visit reattachment of fractured incisal edges using different post systems. PMID- 26843768 TI - Comprehensive rehabilitation of a worn out dentition with complete coverage ceramic restorations. PMID- 26843769 TI - Aesthetic and functional rehabilitation with pressable ceramics. PMID- 26843770 TI - Alveolar ridge split technique for implant placement. PMID- 26843771 TI - Aspiration of an endodontic file. PMID- 26843772 TI - Restoring smile: An integrated prosthodontic approach. PMID- 26843773 TI - Hypohidrotic Ectodermal Dysplasia. PMID- 26843774 TI - A rare case of epidermoid cyst of tongue. PMID- 26843775 TI - Reattachment of subgingival complicated fractures of anterior teeth. PMID- 26843776 TI - Conservative and esthetic management of diastema closure using porcelain laminate veneers. PMID- 26843777 TI - Salvaging a tooth with extensive invasive cervical resorption. PMID- 26843778 TI - Achieving aesthetics in deficient anterior maxillary ridge with a modified screw retained prosthesis for Kennedy's Class III situation. PMID- 26843779 TI - Assessment of Genetic Diversity in Secale cereale Based on SSR Markers. AB - The primary aim of this study was to estimate genetic diversity among Secale cereale L. accessions using 22 previously published simple sequence repeat (SSR) markers. The plant material included 367 rye accessions comprising historical and contemporary cultivars, cultivated materials, landraces, and breeding strains from the Polish breeding company Danko. The studied accessions represented a wide geographical diversity. Several methods were employed to analyze genetic diversity among the Secale cereale L. accessions and to determine population structure: principal coordinate analysis (PCoA), neighbor-joining (NJ), and Bayesian clustering. We also defined a core collection of 25 rye accessions representing over 93 % of SSR alleles. The results of these analyses showed that accessions from the rye gene bank are clearly divergent in comparison with materials received directly from European breeding companies. Our findings suggest also that the genetic pool of current rye cultivars is becoming narrower during breeding processes. The selected panel of SSR markers performed well in detection of genetic diversity patterns and can be recommended for future germplasm characterization studies in rye. PMID- 26843780 TI - Comparative Transcriptome Analysis of Isoetes Sinensis Under Terrestrial and Submerged Conditions. AB - Isoetes L. is an ancient genus of heterosporous lycopsids with a unique phylogenetic position. Repeated adaptations to environmental changes over time have contributed to occupying a variety of niches in Isoetes. However, we know little about how they adapt to the environmental changes, and the sequence resources are very limited in public databases. Isoetes sinensis is an amphibious plant in this genus, alternating frequently between terrestrial and aquatic environments. In this study, I. sinensis was applied to investigate the adaptations under terrestrial (TC) and submerged (ST) conditions using Illumina RNA-sequencing technology. Approximately 87 million high-quality reads were yielded and assembled into 31,619 unigenes with an average length of 1618 bp. Overall, 28,208 unigenes were annotated against the National Center of Biotechnology Information (NCBI), Non-redundant (Nr), Cluster of Orthologous Groups (COG), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Moreover, we identified 1740 differentially expressed genes with 1146 up-regulated and 594 down-regulated genes under TC. GO annotation revealed that stress-relevant categories were remarkably enriched, and KEGG enrichment analysis showed that the phytohormone signalings and carbohydrate metabolism were significantly influenced. Furthermore, a total of 1646 transcription factors (TF) were identified and classified into 54 TF families; among them, 180 TFs were dynamic between terrestrial and submerged conditions. This study is the first report for Isoetes to generate numerous sequences and establish general understandings about the adaptations in the changing environments. The dataset provides a foundation for novel gene discoveries, comparative genomics, functional genomics, and phylogenetics in Isoetes. PMID- 26843781 TI - Sexual aggression by intruders in hooded crow Corvus cornix. AB - The hooded crow Corvus cornix is a west Palaearctic, solitary nesting, monogamous corvid. In the breeding season, populations are characterized by a social organization wherein breeding pairs are territorial and non-breeding individuals, called floaters, live in flocks. During a study of the breeding ecology of the hooded crow, conducted in a protected flooded area, we monitored nests with video cameras. We recorded two separate incidents when intruders attacked a female at the nest. We believe that she remained in the nest in order to prevent the strangers cannibalizing the nestlings by mantling over the brood. The spatio temporal occurrence of these attacks suggests that the observed behaviour is intraspecific sexual aggression wherein non-breeding males mounted an immobilized female. PMID- 26843782 TI - Temporal Averaging Across Stimuli Signaling the Same or Different Reinforcing Outcomes in the Peak Procedure. AB - The present study examined factors that affect temporal averaging in rats when discriminative stimuli are compounded following separate training indicating the availability of reward after different fixed intervals (FI) on a peak procedure. One group of rats, Group Differential, learned that a flashing light stimulus signaled that one type of food pellet reward could be earned for lever pressing after an FI 5 s interval and that a second type of food pellet reward could be earned after an FI 20 s interval in the presence of a tone stimulus. A second group of rats, Group Non-Differential, was similarly trained except that both types of rewards were scheduled across flash and tone trials. When given non reinforced flash + tone compound test trials the interval containing the maximal response rate was no different than on flash alone test trials, although some responding also appeared near the long FI time. After these FI contingencies were reversed (flash signaled FI 20 s and tone signaled FI 5 s), however, further compound test trials more clearly revealed a temporal averaging pattern in both groups. The peak interval was shifted to the right of the FI 5 stimulus. Moreover, Group Differential rats acquired the reversed discrimination somewhat more rapidly than Group Non-Differential rats, and in a final selective satiation test Group Differential rats responded less in later intervals after they had been sated on the FI 20 s reward. These data suggest that temporal averaging in stimulus compound tests occurs even when the stimuli being combined signal qualitatively different rewards, but that decreasing the value of one of those rewards can shift responding away from the relevant time interval in a selective satiation test. However, when an especially salient stimulus (e.g., flashing light) signals a short FI, rats tend to process the compound stimulus more in terms of its individual elements. PMID- 26843783 TI - Intersectionality at Work: Determinants of Labor Supply among Immigrant Latinas. AB - This article borrows from the intersectionality literature to investigate how legal status, labor market position, and family characteristics structure the labor supply of immigrant Latinas in Durham, NC, a new immigrant destination. The analysis takes a broad view of labor force participation, analyzing the predictors of whether or not women work; whether and how the barriers to work vary across occupations; and variation in hours and weeks worked among the employed. I also explicitly investigate the extent to which family constraints interact with other social characteristics, especially legal status, in shaping women's labor market position. Results highlight that immigrant Latinas experience multiple, interrelated constraints on employment owing to their position as low-skill workers in a labor market highly segregated by gender and nativity, to their status as members of a largely undocumented population, and as wives and mothers in an environment characterized by significant work-family conflict. PMID- 26843784 TI - Spatial prioritisation for conserving ecosystem services: comparing hotspots with heuristic optimisation. AB - CONTEXT: The variation in spatial distribution between ecosystem services can be high. Hence, there is a need to spatially identify important sites for conservation planning. The term 'ecosystem service hotspot' has often been used for this purpose, but definitions of this term are ambiguous. OBJECTIVES: We review and classify methods to spatially delineate hotspots. We test how spatial configuration of hotspots for a set of ecosystem services differs depending on the applied method. We compare the outcomes to a heuristic site prioritisation approach (Marxan). METHODS: The four tested hotspot methods are top richest cells, spatial clustering, intensity, and richness. In a conservation scenario we set a target of conserving 10 % of the quantity of five regulating and cultural services for the forest area of Telemark county, Norway. RESULTS: Spatial configuration of selected areas as retrieved by the four hotspots and Marxan differed considerably. Pairwise comparisons were at the lower end of the scale of the Kappa statistic (0.11-0.27). The outcomes also differed considerably in mean target achievement, cost-effectiveness in terms of land-area needed per unit target achievement and compactness in terms of edge-to-area ratio. CONCLUSIONS: An ecosystem service hotspot can refer to either areas containing high values of one service or areas with multiple services. Differences in spatial configuration among hotspot methods can lead to uncertainties for decision-making. This also has consequences for analysing the spatial co-occurrence of hotspots of multiple services and of services and biodiversity. PMID- 26843785 TI - Selective Reduction of Halogenated Nitroarenes with Hydrazine Hydrate in the Presence of Pd/C. AB - A large variety of halogenated nitroarenes have been selectively reduced with hydrazine hydrate in the presence of Pd/C to give the corresponding (halogenated) anilines in good yield. PMID- 26843786 TI - STEADFAST: Psychotherapeutic Intervention Improves Postural Strategy of Somatoform Vertigo and Dizziness. AB - Patients with somatoform vertigo and dizziness (SVD) disorders often report instability of stance or gait and fear of falling. Posturographic measurements indeed indicated a pathological postural strategy. Our goal was to evaluate the effectiveness of a psychotherapeutic and psychoeducational short-term intervention (PTI) using static posturography and psychometric examination. Seventeen SVD patients took part in the study. The effects of PTI on SVD were evaluated with quantitative static posturography. As primary endpoint a quotient characterizing the relation between horizontal and vertical sway was calculated (Q H/V ), reflecting the individual postural strategy. Results of static posturography were compared to those of age- and gender-matched healthy volunteers (n = 28); baseline measurements were compared to results after PTI. The secondary endpoint was the participation-limiting consequences of SVD as measured by the Vertigo Handicap Questionnaire (VHQ). Compared to the healthy volunteers, the patients with SVD showed a postural strategy characterized by stiffening-up that resulted in a significantly reduced body sway quotient before PTI (patients: Q H/V = 0.31 versus controls: Q H/V = 0.38; p = 0.022). After PTI the postural behavior normalized, and psychological distress was reduced. PTI therefore appears to modify pathological balance behaviour. The postural strategy of patients with SVD possibly results from anxious anticipatory cocontraction of the antigravity muscles. PMID- 26843787 TI - Synthesis of enantiopure 1,2-azido and 1,2-amino alcohols via regio- and stereoselective ring-opening of enantiopure epoxides by sodium azide in hot water. AB - A practical and convenient method for the efficient and regio- and stereoselective ring-opening of enantiopure monosubstituted epoxides by sodium azide under hydrolytic conditions is reported. The ring-opening of enantiopure styryl and pyridyl (S)-epoxides by N3- in hot water takes place preferentially at the internal position with complete inversion of configuration to produce (R)-2 azido ethanols with up to 99% enantio- and regioselectivity, while the (S) adamantyl oxirane provides mainly the (S)-1-adamantyl-2-azido ethanol in excellent yield. In general, 1,2-amino ethanols were obtained in high yield and excellent enantiopurity by the reduction of the chiral 1,2-azido ethanols with PPh3 in water/THF, and then converted into the Boc or acetamide derivatives. PMID- 26843788 TI - Th17 Cells in Type 1 Diabetes: Role in the Pathogenesis and Regulation by Gut Microbiome. AB - Type 1 diabetes (T1D) is an autoimmune disease which is characterized by progressive destruction of insulin producing pancreatic islet beta cells. The risk of developing T1D is determined by both genetic and environmental factors. A growing body of evidence supports an important role of T helper type 17 (Th17) cells along with impaired T regulatory (Treg) cells in the development of T1D in animal models and humans. Alteration of gut microbiota has been implicated to be responsible for the imbalance between Th17 and Treg cells. However, there is controversy concerning a pathogenic versus protective role of Th17 cells in murine models of diabetes in the context of influence of gut microbiota. In this review we will summarize current knowledge about Th17 cells and gut microbiota involved in T1D and propose Th17 targeted therapy in children with islet autoimmunity to prevent progression to overt diabetes. PMID- 26843790 TI - Race/ethnic Differences in Post-stroke Depression (PSD): Findings from the Stroke Warning Information and Faster Treatment (SWIFT) Study. AB - OBJECTIVE: Post-stroke depression (PSD) is common and associated with poor stroke outcomes, but few studies have examined race/ethnic disparities in PSD. Given the paucity of work and inconsistent findings in this important area of research, our study aimed to examine race/ethnic differences in depression in a multi-ethnic cohort of stroke patients. DESIGN: Longitudinal. SETTING: Prospective trial of a post-stroke educational intervention. PARTICIPANTS: 1,193 mild/moderate ischemic stroke/transient ischemic attack (TIA) patients. MAIN OUTCOME MEASURES: We used the Center for Epidemiologic Studies Depression (CES-D) Scale to assess subthreshold (CES-D score 8-15) and full (CES-D score >= 16) depression at one month ("early") and 12 months ("late") following stroke. Multinomial logistic regression analyses examined the association between race/ethnicity and early and late PSD separately. RESULTS: The prevalence of subthreshold and full PSD was 22.5% and 32.6% in the early period and 22.0% and 27.4% in the late period, respectively. Hispanics had 60% lower odds of early full PSD compared with non Hispanic Whites after adjusting for other covariates (OR=.4, 95% CI: .2, .8). Race/ethnicity was not significantly associated with late PSD. CONCLUSIONS: Hispanic stroke patients had half the odds of PSD in early period compared with Whites, but no difference was found in the later period. Further studies comparing trajectories of PSD between race/ethnic groups may further our understanding of race/ethnic disparities in PSD and help identify effective interventions. PMID- 26843789 TI - Overexpression of Kinesin Associated Protein 3 (KIFAP3) in Breast Cancer. AB - Gene expression profiling studies on breast cancer have generated catalogs of differentially expressed genes. However, many of these genes have not been investigated for their expression at the protein level. It is possible to systematically evaluate such genes in a high-throughput fashion for their overexpression at the protein level using breast cancer tissue microarrays. Our strategy involved integration of information from publicly available repositories of gene expression to prepare a list of genes upregulated at the mRNA level in breast cancer followed by curation of the published literature to identify those genes that were not tested for overexpression at the protein level. We identified Kinesin Associated Protein 3 (KIFAP3) as one such molecule for further validation at the protein level. Immunohistochemical labeling of KIFAP3 using breast cancer tissue microarrays revealed overexpression of KIFAP3 protein in 84% (240/285) of breast cancers indicating the utility of our integrated approach of combining computational analysis with experimental biology. PMID- 26843792 TI - Neighborhood Characteristics are Associated with Racial and Gender Variation in Walking among Older Adults: the Cardiovascular Health Study. AB - OBJECTIVE: To examine variation by race and gender in the association between neighborhood socioeconomic status and walking among community-dwelling older adults. DESIGN: Cross-sectional. SETTING: Cardiovascular Health Study, a longitudinal population-based cohort. PARTICIPANTS: 4,849 adults, aged > 65 years. MEASUREMENTS: Participants reported the number of city blocks walked in the prior week. Neighborhood socioeconomic status (NSES) was measured at the level of the census tract. Negative binominal regression models were constructed to test the association between NSES and blocks walked. In the fully adjusted models, we included two-way and three-way interaction terms among race, gender, and NSES. RESULTS: In adjusted analyses, among White residents in the lowest NSES quartile (most disadvantaged), men walked 64% more than women (P<.001), while in the highest NSES (most advantaged), men walked 43% more than women (P<.001). Among African American residents in the lowest NSES quartile, men walked 196% more blocks than women (P<.001). CONCLUSIONS: Female gender is more strongly associated with walking for African Americans than for Whites in low SES neighborhoods but had a similar association with walking for both African Americans and Whites in high SES neighborhoods. PMID- 26843791 TI - Addressing Stroke Risk Factors in Black and White Americans: Findings from the National Health and Nutrition Examination Survey, 2009-2010. AB - OBJECTIVE: Recurrent stroke affects 5%-15% of stroke survivors, is higher among Blacks, and preventable with secondary stroke prevention medications. Our study aimed to examine racial differences in risk factors being addressed (defined as either on active treatment or within guideline levels) among stroke survivors and those at risk for stroke. METHODS: A cross-sectional study using NHANES 2009-2010 standardized interviews of Whites and Blacks aged >=18 years. Risk factors were defined as being addressed if: 1) for hypertension, SBP <140, DBP <90 (SBP<130, DBP<80 for diabetics) or using BP-lowering medications; 2) for current smoking, using cessation medications; and 3) for hyperlipidemia, LDL<100 (LDL<70 for stroke survivors) or using lipid-lowering medications. Participants were stratified by stroke history. Prevalence of addressed risk factors was compared by race. RESULTS: Among 4005 participants (mean age 48, 52% women, 15% Black), 4% reported a history of stroke. Among stroke survivors, there were no statistically significant differences in Blacks and Whites having their hypertension or hyperlipidemia addressed. Among stroke naive participants, the prevalence of addressed hypertension (P<.01) and hyperlipidemia (P<.01) was lower in Blacks compared with Whites. CONCLUSIONS: We found that addressed hypertension and hyperlipidemia in stroke naive participants were significantly lower in Blacks than Whites. Our observations call attention to areas that require further investigation, such as why Black Americans may not be receiving evidence-based pharmacologic therapy for hypertension and hyperlipidemia or why Black Americans are not at goal blood pressure or goal LDL. A better understanding of this information is critical to preventing stroke and other vascular diseases. PMID- 26843793 TI - A Brief, Multifaceted, Generic Intervention to Improve Blood Pressure Control and Reduce Disparities Had Little Effect. AB - BACKGROUND: Poor blood pressure (BP) control and racial disparities therein may be a function of clinical inertia and ineffective communication about BP care. METHODS: We compared two different interventions (electronic medical record reminder for BP care (Reminder only, [RO]), and clinician training on BP care related communication skills plus the reminder (Reminder + Training, [R+T]) with usual care in three primary care clinics, examining BP outcomes among 8,866 patients, and provider-patient communication and medication adherence among a subsample of 793. RESULTS: Clinician counseling improved most at R+T. BP improved overall; R+T had a small but significantly greater reduction in diastolic BP (DBP; -1.7 mm Hg). White patients at RO experienced greater overall improvements in BP control. Site and race disparities trends suggested that disparities decreased at R+T, either stayed the same or decreased at Control; and stayed the same or increased at RO. CONCLUSIONS: More substantial or racial/ethnically tailored interventions are needed. PMID- 26843794 TI - The Effects of Job Instability and Financial Strain on C-Reactive Protein in a Sample of Mexican Immigrants. AB - OBJECTIVE: Mexican immigrants have lower cardiovascular disease risk than US citizens, but risk increases with level of acculturation. Our study investigated whether job stress and financial strain would be related to inflammation (C reactive protein), lipids, and blood pressure, and if they would play a role in the acculturation process in Mexican immigrants. METHODS: A sample of 310 Mexican immigrants living in the United States were studied on measures of job stress, financial strain, acculturation, and cardiovascular disease risk factors (C reactive protein, lipids, and blood pressure). RESULTS: Job instability, financial strain, and acculturation, were related to inflammation, but psychological demands and decision latitude were not related. Lipids and blood pressure were not related to the variables of interest. Body mass index (BMI) was related to both increased acculturation and inflammation, and when controlling for BMI, acculturation was no longer a significant predictor of inflammation. Job instability and financial strain remained significant predictors of inflammation after controlling for BMI, sex, and age. Job instability and financial strain were not related to acculturation, suggesting that these factors are significant stressors for both newly arrived and more established immigrants. CONCLUSIONS: Job instability and financial strain predict increased inflammation in Mexican immigrants but they do not play a role in the relationship between acculturation and C-reactive protein. The effects of acculturation on inflammation in this study were mediated by BMI. PMID- 26843795 TI - Sex and Race-Ethnicity Secular Trends in Mean and Elevated Red Blood Cell Distribution Width Among Adults in the United States, 1999-2012. AB - OBJECTIVE: Red blood cell distribution width (RDW) has been shown to associate with increased risk of cardiovascular and non-cardiovascular death. To our knowledge, no study has examined secular trends in RDW over the last decade. DESIGN: Serial cross-sectional design. SETTING: Data from the National Health and Nutrition Examination Survey (NHANES), 1999-2012, were used. PATIENTS: 34,171 adults. MAIN OUTCOME MEASURES: RDW was assessed from a blood sample derived from the coefficient of variation of the red cell volume distribution histogram and reported as a percent. Elevated RDW was defined as an RDW > 14.6%. RESULTS: The overall age-adjusted mean RDW increased progressively and significantly (P<.05) from 12.59% in 1999-2000 to 12.89% in 2011-2012. The overall age-adjusted prevalence of elevated RDW increased progressively and significantly (P<.05) from 4.01% in 1999-2000 to 6.25% in 2011-2012. Statistically significant increases over this time period also occurred among non-Hispanic White women, non-Hispanic Black men and women, and Mexican American men and women. Across all sex and race ethnicity combinations, women, compared with men, had higher RDW and larger increases over time in mean and elevated RDW. CONCLUSIONS: Mean and elevated RDW has progressively increased from 1999-2012 among adults in the United States, with increases observed among non-Hispanic Whites, Blacks, and Mexican Americans. Future research is needed to describe the determinants and implications of this RDW rise, as well as explanations for why a greater RDW change has occurred among women. PMID- 26843796 TI - Results from the Trial Using Motivational Interviewing, Positive Affect, and Self Affirmation in African Americans with Hypertension (TRIUMPH). AB - OBJECTIVE: Our objective was to determine the effectiveness of combining positive affect and self-affirmation strategies with motivational interviewing in achieving blood pressure control among hypertensive African Americans (AA) compared with AA hypertensives in an education-only control group. DESIGN: Randomized trial. SETTING: Ambulatory practices in the South Bronx and Harlem, New York City. PARTICIPANTS: African American adults with uncontrolled hypertension. INTERVENTIONS: Participants were randomized to a positive affect and self-affirmation intervention or an education control group. The positive affect and self-affirmation intervention involved having participants think about things that made them happy and that reminded them of their core values on a daily basis. These strategies were reinforced every two months through motivational interviewing. The control arm received a workbook of strategies on blood pressure control. All participants were called every two months for one year. MAIN OUTCOMES: Blood pressure control rate. RESULTS: A total of 238 participants were randomized. The average age was 56 +/- 11 years, approximately 70% were female, 80% were not married, and up to 70% had completed high school. There was no difference in control rates between the intervention and the control group. However, at one year, female participants were more likely to be controlled. Participants with high depressive symptoms or high perceived stress at baseline were less likely to be controlled. CONCLUSIONS: While this study did not demonstrate an intervention effect, it does provide important insight into the psychosocial factors that may underlie blood pressure control in African Americans. Implications for future behavioral intervention trials are discussed. PMID- 26843798 TI - Ethnic Identity and Implicit Anti-fat Bias: Similarities and Differences between African American and Caucasian Women. AB - Research using self-report or explicit measures of body image suggests African American women have a more accepting view of larger figures than non-Hispanic White (NHW) women. However, increasing research indicates that explicit views may vary from those held at a deeper, implicit level. Our study examined whether African American women held an implicit negative bias toward overweight/fat individuals, despite a greater explicit acceptance of larger body size. Additionally, ethnic identity was measured to assess if strength of identity related to bias. Anti-fat bias was compared within and between ethnic groups using an Implicit Association Test (IAT), which measures the strength of automatic associations between two concepts. This online IAT measured spontaneous thoughts about figures of various body weights (underweight, overweight, obese) and positive and negative terms (eg, attractive and unattractive or healthy and unhealthy). A pervasive anti-fat bias was found in African American as well as NHW women. For both groups, this bias was related to ethnic identity when thinking about figure size and health. Specifically, African American women with lower ethnic identity were more negatively biased and NHW women with higher ethnic identity were more negatively biased. Findings from this study indicate that implicitly there are few differences in the way these two ethnicities classify heavy figures, and therefore African Americans may not be immune to weight stigma. Given the prevalence of obesity and the lack of research on weight stigma among African American women, there is need to address this issue and its impact on well-being. PMID- 26843797 TI - Race-specific Association of Caesarean-Section Delivery with Body Size at Age 2 Years. AB - OBJECTIVE: African American children are at higher risk of obesity than White children and African American women are more likely to undergo caesarean-section (CS) delivery than White women. CS is associated with childhood obesity; however, little is known whether this relationship varies by race. We examined if the association of CS with obesity at age 2 years varied by race. DESIGN: Longitudinal birth cohort. SETTING: Birth cohort conducted in a health care system in metropolitan Detroit, Michigan with follow-up at age 2 years. PARTICIPANTS: 639 birth cohort participants; 367 children (57.4%) were born to African American mothers and 230 (36.0%) children were born via CS. MAIN OUTCOME MEASURES: Obesity defined as body mass index >=95th percentile at age 2 years. RESULTS: Slightly more children of African American (n=37; 10.1%) than non African American mothers (n=18; 6.6%) were obese (P=.12). There was evidence of effect modification between race and delivery mode with obesity at age 2 years (interaction P=.020). In children of African American mothers, CS compared to vaginal birth was associated with a significantly higher odds of obesity (aOR=2.35 (95% CI: 1.16, 4.77), P=.017). In contrast, delivery mode was not associated with obesity at age 2 years in children of non-African American mothers (aOR=.47 (95% CI: .13, 1.71), P=.25). CONCLUSIONS: There is evidence for a race-specific effect of CS on obesity at age 2 years; potential underlying mechanisms may be racial differences in the developing gut microbiome or in epigenetic programming. Future research is needed to determine if this racial difference persists into later childhood. PMID- 26843799 TI - Higher Motivation for Weight Loss in African American than Caucasian Rural Patients with Hypertension and/or Diabetes. AB - OBJECTIVE: To examine the relationship between race/ethnicity and motivation for weight loss and motivation for exercise among patients with chronic disease. DESIGN: Cross-sectional. SETTING: Our study took place within a network of federally qualified health centers (FQHCs) in the rural southern United States. PATIENTS OR PARTICIPANTS: 463 active FQHC patients with diabetes and/or hypertension identifying as African American, White Hispanic, or non-Hispanic White participated in our study. MAIN OUTCOME MEASURES: Primary outcomes were assessed using standardized measures of motivation for a) weight loss; and b) hypertension per the Transtheoretical Model. RESULTS: Multivariate logistic regression revealed that, when controlling for age, sex, education status, employment status, poverty, comorbidity, and weight status, there were no significant differences in motivation for exercise among the different racial/ethnic groups (P=.361). However, when controlling for the same factors, there was a significant difference in motivation for weight loss, with African American participants more than twice as likely as non-Hispanic White participants to be motivated to lose weight (ORADJ = 2.430, P=.002). CONCLUSIONS: Our study suggests that, among rural patients with obesity-related chronic disease, there is a significant variation in motivation to lose weight between racial/ethnic groups. This underscores the importance of culturally tailoring interventions and in considering motivation for change when promoting weight loss behaviors. Additional implications for intervention development and delivery are discussed. PMID- 26843800 TI - Racial and Economic Disparities in Diabetes in a Large Primary Care Patient Population. AB - OBJECTIVE: We sought to determine if, after adjusting for economic status, race is an independent risk factor for glycemic control among diabetic patients in a large primary care patient population. DESIGN SETTING PARTICIPANTS: We performed a retrospective chart review of 264,000 primary care patients at our large, urban academic medical center to identify patients with a diagnosis of diabetes (n=25,123). Zip code was used to derive median income levels using US Census Bureau demographic information. Self-reported race was extracted from registration data. MAIN OUTCOME MEASURES: The prevalence of diabetes, average glycated hemoglobin (A1c), and prevalence of uncontrolled diabetes of White and Black patients at all income levels were determined. RESULTS: White patients had a lower average A1c level and a lower prevalence of diabetes than Black patients in all income quartiles (P<.001). Among White patients, the prevalence of diabetes (P<.001), uncontrolled diabetes (P<.001), and A1c level (P=.014) were inversely proportional to income level. No significant difference in the prevalence of diabetes (P=.214), A1c level (P=.282), or uncontrolled diabetes related to income was seen in Black patients (P=.094). CONCLUSIONS: Race had an independent association with diabetes prevalence and glycemic control. Our study does not support two prominent theories that economic and insurance status are the main factors in diabetes disparities, as we attempted to control for economic status and nearly every patient had insurance. It will be important for future analysis to explore how health care system factors affect these observed gaps in quality. PMID- 26843801 TI - Compliance with a New York State 2010 HIV Testing Law: Is There Racial/Ethnic Bias in HIV Testing? Experience of Monroe County, New York, 2012. AB - BACKGROUND: While routine HIV testing in the general population is a national recommendation, actual practice may vary. PURPOSE: To determine risk factors associated with HIV testing after the adoption of a New York State law in 2010 mandating that health care providers offer HIV testing in all clinical settings. METHODS: Survey data from Monroe County, New York, were collected in 2012 for adults aged 18-64 years and analyzed in 2014. Logistic regression was used to identify risk factors independently associated with HIV testing and high-risk behavior. RESULTS: Among adults aged 18-34, fewer Whites were offered HIV testing in the past year by their doctors compared with Blacks (34% vs 64%) despite having similar rates of any HIV high-risk behavior (20% overall). For adults aged 35-64 years, fewer Whites than Blacks were ever tested for HIV (42% vs 71%), offered HIV testing in past year (17% vs 40%), and reported any HIV high-risk behavior (3% vs 13%). Latinos showed intermediate levels. With logistic regression analysis, ever tested for HIV was independently associated with only race/ethnicity; offered HIV testing in the past year was associated with females, Blacks and Latinos, aged 18-34 years, and having a routine health checkup in past year; any HIV high-risk behavior was associated with only younger age. CONCLUSIONS: To improve HIV testing rates as well as compliance with state laws and national guidelines, targeted efforts should be considered that improve perceptions of risk and emphasize the value of routine HIV screening, including those directed at White adults and their health care providers. PMID- 26843802 TI - Prevalence of Metabolic Syndrome and its Related Risk Factors in the City of Oran, Algeria: the ISOR Study. AB - BACKGROUND: Aging and lifestyle changes had led to an epidemiological transition, with a significant impact on the incidence of cardiovascular diseases in North Africa. OBJECTIVE: The aim of this study was to determine the prevalence of metabolic syndrome and its associated factors, which were unknown, among an urban population in Algeria. METHODS: During 2007-2009, 787 individuals aged 30-64 years, randomly selected from the list of insured persons residing in the city of Oran, participated in a clinical, anthropometric and biological survey. Participants were classified according to the National Cholesterol Education Program - Adult Treatment Panel (NCEP-ATP) III definition of metabolic syndrome. RESULTS: The prevalence of metabolic syndrome was 20%, higher in women than men (25.9 vs 13.7%; P<.0001). Among the components of the syndrome, the most common risk factors observed in women were a low high-density lipoprotein (HDL) cholesterol concentration (60.4% vs 44.2% in men) and abdominal obesity (46.8% vs 30.1% in men) whereas men displayed more high blood pressure (42.5% vs 34.8% in women). In men, metabolic syndrome was more frequent in married and highly educated participants. In contrast, women with a high level of education and who had an intermediate level of physical activity seemed to be protected. CONCLUSIONS: Metabolic syndrome, prevalent in the urban population of North Algeria, is associated with a high proportion of low HDL-cholesterol and abdominal obesity, especially among women. There is a need for prevention strategies involving promotion of physical activity for the whole population and screening for hypertension among men. PMID- 26843803 TI - Waterpipe Tobacco Smoking among Arab Youth; a Cross-Country Study. AB - OBJECTIVE: Waterpipe tobacco smoking (WTS) is considered a global epidemic that is spreading among youth. Our analysis was conducted to compare the national baseline prevalence rate estimates of WTS among Arab boys and girls. DESIGN SETTING AND PARTICIPANTS: The Global Youth Tobacco Survey (GYTS) is a school based survey using standardized self-administered questionnaires; it employs a two-stage cluster sampling technique to obtain a representative sample of youth (13-15 years of age). We conducted a secondary data analysis of nationally representative GYTSs available from 16 Arab countries. MAIN MEASURES: Youth who self-reported smoking waterpipe at least once in the past 30 days were considered to be current waterpipe tobacco smokers. National weighted WTS prevalence rate estimates along with respective 95% confidence intervals were reported for boys and girls. RESULTS: Pooled GYTS data from 16 Arab countries yielded a total of 31,359 youth. Overall, 10.6% of the respondents were current waterpipe tobacco smokers, with boys (13.7%) having significantly higher estimates than girls (7.2%). Overall, current WTS prevalence rate estimates ranged from .9% in Oman to 34.2%, in Lebanon. The WTS epidemic was more predominant among boys and girls, respectively, in the West Bank (42.8% and 24.2%), Lebanon (38.6% and 30.5%) and Jordan (25.7% and 14.5%). CONCLUSION: Among Arab boys and girls, WTS represents a growing strain of the tobacco epidemic that requires immediate attention. PMID- 26843804 TI - Neighborhood and Individual Socioeconomic Status and Asthma Incidence in African American Women. AB - OBJECTIVE: Individual socioeconomic status (SES) has been associated with asthma incidence but whether neighborhood SES has an influence is unknown. We assessed the contributions of neighborhood socioeconomic status (SES), neighborhood housing density, neighborhood racial composition, and individual SES to the development of adult-onset asthma in Black women, accounting for other known or suspected risk factors. DESIGN AND PARTICIPANTS: Prospective cohort study conducted among 47,779 African American women followed with biennial health questionnaires from 1995 to 2011. METHODS AND MAIN OUTCOME MEASURES: Incident asthma was defined as new self-report of doctor-diagnosed asthma with concurrent use of asthma medication. We assessed neighborhood SES, indicated by census variables representing income, education, and wealth, and housing density and % African American population, as well as individual SES, indicated by highest education of participant/spouse. Cox proportional hazards models were used to derive multivariable hazard ratios (HRs) and 95% CIs for the association of individual SES and neighborhood variables with asthma incidence. RESULTS: During a 16-year follow-up period, 1520 women reported incident asthma. Neighborhood factors were not associated with asthma incidence after control for individual SES, body mass index, and other factors. Compared with college graduates, the multivariable HR for asthma was 1.13 (95% CI 1.00-1.28) for women with some college education and 1.23 (95% CI 1.05-1.44) for women with no more than a high school education. CONCLUSIONS: Individual SES, but not neighborhood SES or other neighborhood factors, was associated with the incidence of adult-onset asthma in this population of African American women. PMID- 26843806 TI - Commentary: Persistence and Health-Related Consequences of the Model Minority Stereotype for Asian Americans. AB - Fifty years ago, the term model minority was coined to describe the extraordinary ability of Asian Americans to overcome hardship to succeed in American society. Less well-known is how the model minority stereotype was cultivated within the context of Black-White race relations during the second half of the 20th century, and how this stereotype, in turn, has contributed to the understanding and prioritization of health disparities experienced by Asian Americans. The objectives of this article are to define the model minority stereotype, present its controversies, and provide examples of its social and health-related consequences (ie, implications for obesity and tobacco) across multiple levels of society and institutions. A salient theme throughout the examples provided is the limitation of data presented at the aggregate level across all Asian subgroups which masks meaningful disparities. The intent is to increase the visibility of Asian Americans as a racial/ethnic minority group experiencing chronic disease health disparities and deserving of health-related resources and consideration. PMID- 26843807 TI - Developing Interventions for Overweight and Obese Children using Electronic Health Records Data. AB - Childhood obesity and the resulting co-morbid conditions have become a massive burden for primary caregivers in West Virginia and across the United States. Building culturally sensitive clinical interventions to meet population health needs presents a multi-factorial challenge. Historically it has been is difficult to accurately assess the demographic characteristics of clinic populations. Fortunately, the use of electronic health records (EHR) has created a major shift in clinical documentation and ability to routinely collect essential demographic and clinical data. While data for Meaningful Use under the Centers for Medicare and Medicaid Services is increasingly used to evaluate clinical care and outcomes, use of EHR data outside of the Meaningful Use umbrella has not received sufficient attention. This study explores use of EHR data beyond Meaningful Use to obtain demographic characteristics of an obese and overweight pediatric population in a rural primary care center for the purpose of informing appropriate, locally relevant intervention strategies. We find that the breadth and depth of information recorded on each patient can collectively provide valuable information to describe and evaluate the clinic population, identify priority areas to address, and measure change over time. Application of EHR data to understand the demographic characteristics of this particular patient population highlights the ability to identify target patient populations, uncover critical patient-level and population-level outcomes, inform intervention development and implementation, and add value to efforts in quality improvement systems transformation. Use of EHR data outside of the Meaningful Use umbrella needs increased attention in primary care. PMID- 26843805 TI - The Healthy Community Neighborhood Initiative: Rationale and Design. AB - OBJECTIVE: To describe the design and rationale of the Healthy Community Neighborhood Initiative (HCNI), a multi-component study to understand and document health risk and resources in a low-income and minority community. DESIGN: A community-partnered participatory research project. SETTING: A low income, biethnic African American and Latino neighborhood in South Los Angeles. PARTICIPANTS: Adult community residents aged >18 years. MAIN OUTCOME MEASURES: Household survey and clinical data collection; neighborhood characteristics; neighborhood observations; and community resources asset mapping. RESULTS: We enrolled 206 participants (90% of those eligible), of whom 205 completed the household interview and examination, and 199 provided laboratory samples. Among enrollees, 82 (40%) were aged >50 years and participated in functional status measurement. We completed neighborhood observations on 93 street segments; an average of 2.2 (SD=1.6) study participants resided on each street segment observed. The community asset map identified 290 resources summarized in a Community Resource Guide given to all participants. CONCLUSIONS: The HCNI community-academic partnership has built a framework to assess and document the individual, social, and community factors that may influence clinical and social outcomes in a community at high-risk for preventable chronic disease. Our project suggests that a community collaborative can use culturally and scientifically sound strategies to identify community-centered health and social needs. Additional work is needed to understand strategies for developing and implementing interventions to mitigate these disparities. PMID- 26843808 TI - Contact Between Birth and Adoptive Families During the First Year Post-Placement: Perspectives of Lesbian, Gay, and Heterosexual Parents. AB - Despite growing visibility of lesbian- and gay-parent adoption, only one qualitative study has examined birth family contact among adoptive families with lesbian and gay parents (Goldberg, Kinkler, Richardson, & Downing, 2011). We studied adoptive parents' (34 lesbian, 32 gay, and 37 heterosexual; N = 103 families) perspectives of birth family contact across the first year post placement. Using questionnaire and interview data, we found few differences in openness dynamics by parental sexual orientation. Most reported some birth mother contact, most had legally finalized their adoption, and few described plans to withhold information from children. We discuss implications for clinical practice, policy, and research. PMID- 26843809 TI - Maximum Entropy Estimation of Probability Distribution of Variables in Higher Dimensions from Lower Dimensional Data. AB - A common statistical situation concerns inferring an unknown distribution Q(x) from a known distribution P(y), where X (dimension n), and Y (dimension m) have a known functional relationship. Most commonly, n <= m, and the task is relatively straightforward for well-defined functional relationships. For example, if Y1 and Y2 are independent random variables, each uniform on [0, 1], one can determine the distribution of X = Y1 + Y2; here m = 2 and n = 1. However, biological and physical situations can arise where n > m and the functional relation Y->X is non unique. In general, in the absence of additional information, there is no unique solution to Q in those cases. Nevertheless, one may still want to draw some inferences about Q. To this end, we propose a novel maximum entropy (MaxEnt) approach that estimates Q(x) based only on the available data, namely, P(y). The method has the additional advantage that one does not need to explicitly calculate the Lagrange multipliers. In this paper we develop the approach, for both discrete and continuous probability distributions, and demonstrate its validity. We give an intuitive justification as well, and we illustrate with examples. PMID- 26843810 TI - Beyond the Ribosome: Extra-translational Functions of tRNA Fragments. AB - High-throughput sequencing studies of small RNAs reveal a complex milieu of noncoding RNAs in biological samples. Early data analysis was often limited to microRNAs due to their regulatory nature and potential as biomarkers; however, many more classes of noncoding RNAs are now being recognized. A class of fragments initially excluded from analysis were those derived from transfer RNAs (tRNAs) because they were thought to be degradation products. More recently, critical cellular function has been attributed to tRNA fragments (tRFs), and their conservation across all domains of life has propelled them into an emerging area of scientific study. The biogenesis of tRFs is currently being elucidated, and initial studies show that a diverse array of tRFs are generated from all parts of a tRNA molecule. The goal of this review was to present what is currently known about tRFs and their potential as biomarkers for the earlier detection of disease. PMID- 26843811 TI - Parental Support, Mental Health, and Alcohol and Marijuana Use in National and High-Risk African-American Adolescent Samples. AB - African-American adolescents experience disproportionate rates of negative consequences of substance use despite using substances at average or below average rates. Due to underrepresentation of African-American adolescents in etiological literature, risk and protective processes associated with their substance use require further study. This study examines the role of parental support in adolescents' conduct problems (CPs), depressive symptoms (DSs), and alcohol and marijuana use in a national sample and a high-risk sample of African American adolescents. In both samples, parental support was inversely related to adolescent CPs, DSs, and alcohol and marijuana use. CPs, but not DSs, partially mediated the relation of parental support to substance use. Results were consistent across the national and high-risk samples, suggesting that the protective effect of parental support applies to African-American adolescents from a range of demographic backgrounds. PMID- 26843812 TI - Big Data Application in Biomedical Research and Health Care: A Literature Review. AB - Big data technologies are increasingly used for biomedical and health-care informatics research. Large amounts of biological and clinical data have been generated and collected at an unprecedented speed and scale. For example, the new generation of sequencing technologies enables the processing of billions of DNA sequence data per day, and the application of electronic health records (EHRs) is documenting large amounts of patient data. The cost of acquiring and analyzing biomedical data is expected to decrease dramatically with the help of technology upgrades, such as the emergence of new sequencing machines, the development of novel hardware and software for parallel computing, and the extensive expansion of EHRs. Big data applications present new opportunities to discover new knowledge and create novel methods to improve the quality of health care. The application of big data in health care is a fast-growing field, with many new discoveries and methodologies published in the last five years. In this paper, we review and discuss big data application in four major biomedical subdisciplines: (1) bioinformatics, (2) clinical informatics, (3) imaging informatics, and (4) public health informatics. Specifically, in bioinformatics, high-throughput experiments facilitate the research of new genome-wide association studies of diseases, and with clinical informatics, the clinical field benefits from the vast amount of collected patient data for making intelligent decisions. Imaging informatics is now more rapidly integrated with cloud platforms to share medical image data and workflows, and public health informatics leverages big data techniques for predicting and monitoring infectious disease outbreaks, such as Ebola. In this paper, we review the recent progress and breakthroughs of big data applications in these health-care domains and summarize the challenges, gaps, and opportunities to improve and advance big data applications in health care. PMID- 26843813 TI - Phospholipid Scramblases. AB - The distribution of phospholipid types between the two leaflets of a membrane bilayer is a controlled feature of membrane structure. One of the two membrane catalytic activities governing this distribution randomizes the composition of the two leaflets-the phospholipid scramblases. Two proteins (Xkr8 and TMEM16F) required for the activation of these activities have been identified. One of these proteins (TMEM16F) is quite clearly a scramblase itself and provides insight into the mechanism by which transbilayer phospholipid movement is facilitated. PMID- 26843815 TI - A Case of Nonfatal Ventricular Arrhythmia Due to Thyrotoxic Periodic Paralysis in a Saudi Patient as an Initial Presentation of Graves' Disease. AB - Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism characterized by recurrent muscle weakness and hypokalemia. It has been commonly reported in non-Asian populations. Four cases were reported in Saudis so far, and one had a life-threatening arrhythmia. We describe an additional case of a 28-year-old apparently healthy Saudi male patient, who presented with acute paraparesis associated with hypokalemia (K: 2.0 mmol/L), complicated by ventricular tachycardia and cardiac arrest. He was successfully resuscitated and his hypokalemia was corrected. A diagnosis of Graves' disease associated with TPP was made. He was initially treated with carbimazole and beta blockers and then given a definitive therapy with radioactive iodine, which showed a good response. This case highlights the importance of early recognition and prompt treatment of TPP as a differential diagnosis for muscle weakness. A brief review of TPP and associated arrhythmia is included. PMID- 26843816 TI - Effect of Korean Red Ginseng treatment on the gene expression profile of diabetic rat retina. AB - BACKGROUND: Korean Red Ginseng (KRG) is a herbal medicine used in Asian countries and is very popular for its beneficial biological properties. Diabetes mellitus (DM) and its complications are rapidly becoming a global public health concern. The literature on transcriptional changes induced by KRG in rat models of diabetic retinopathy is limited. Considering these facts, we designed this study to determine whether retinopathy-associated genes are altered in retinas of rats with DM and whether the induced changes are reversed by KRG. METHODS: Male Sprague-Dawley rats were intravenously injected with streptozotocin (50 mg/kg body weight) to induce DM, following which, KRG powder (200 mg/kg body weight) was orally administered to the KRG-treated DM rat group for 10 wks. The rats were then sacrificed, and their retinas were harvested for total RNA extraction. Microarray gene expression profiling was performed on the extracted RNA samples. RESULTS: From among > 31,000 genes investigated, the expression of 268 genes was observed to be upregulated and that of 58 genes was downregulated, with twofold altered expression levels in the DM group compared with those in the control group. Moreover, 39 genes were upregulated more than twofold and 84 genes were downregulated in the KRG-treated group compared to the DM group. The expression of the genes was significantly reversed by KRG treatment; some of these genes were analyzed further to verify the results of the microarray experiments. CONCLUSION: Taken together, our data suggest that reversed changes in the gene expression may mediate alleviating activities of KRG in rats with diabetic retinopathy. PMID- 26843817 TI - A UPLC/MS-based metabolomics investigation of the protective effect of ginsenosides Rg1 and Rg2 in mice with Alzheimer's disease. AB - BACKGROUND: Alzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated. METHODS: Ultra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively. RESULTS: The impaired cognitive function and increased hippocampal Abeta deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice. CONCLUSION: These results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G Rg1 and G-Rg2 on AD. PMID- 26843818 TI - Immunological benefits by ginseng through reciprocal regulation of Th17 and Treg cells during cyclosporine-induced immunosuppression. AB - BACKGROUND: It is not clear whether ginseng affects cyclosporine A (CsA)-induced desirable immunosuppressive action. In this study, we evaluated the immunological influence of combined treatment of ginseng with CsA. METHODS: Using CD4+ T cells from mouse spleens stimulated with the T cell receptor (TCR) or allogeneic antigen-presenting cells (APCs), we examined the differentiation of naive T cells into T helper 1 (Th1), Th2, Th17, and regulatory T cells (Tregs), and their cytokine production during treatment by Korean Red Ginseng extract (KRGE) and/or CsA. The influence of KRGE on the allogeneic T cell response was evaluated by mixed lymphocyte reaction (MLR). We also evaluated whether signal transducer and activator of transcription 3 (STAT3) and STAT5 are implicated in this regulation. RESULTS: Under TCR stimulation, KRGE treatment did not affect the population of CD4+interferon gamma (IFNgamma)+ and CD4+interleukin (IL)-4+ cells and their cytokine production compared with CsA alone. Under the Th17-polarizing condition, KRGE significantly reduced the number of CD4+IL-17+ cells and CD4+/phosphorylated STAT3 (p-STAT3)+ cells, but increased the number of CD4+CD25+forkhead box P3 (Foxp3)+ cells and CD4+/p-STAT5+ cells compared with CsA alone. In allogeneic APCs-stimulated CD4+ T cells, KRGE significantly decreased total allogeneic T cell proliferation. Consistent with the effects of TCR stimulation, KRGE reduced the number of CD4+IL-17+ cells and increased the number of CD4+CD25+Foxp3+ cells under the Th17-polarizing condition. CONCLUSION: KRGE has immunological benefits through the reciprocal regulation of Th17 and Treg cells during CsA-induced immunosuppression. PMID- 26843819 TI - Effects of cultivation ages and modes on microbial diversity in the rhizosphere soil of Panax ginseng. AB - BACKGROUND: Panax ginseng cannot be cultivated on the same land consecutively for an extended period, and the underlying mechanism regarding microorganisms is still being explored. METHODS: Polymerase chain reaction and denaturing gradient gel electrophoresis (PCR-DGGE) and BIOLOG methods were used to evaluate the microbial genetic and functional diversity associated with the P. ginseng rhizosphere soil in various cultivation ages and modes. RESULTS: The analysis of microbial diversity using PCR-DGGE showed that microbial communities were significantly variable in composition, of which six bacterial phyla and seven fungal classes were detected in P. ginseng soil. Among them, Proteobacteria and Hypocreales dominated. Fusarium oxysporum, a soilborne pathogen, was found in all P. ginseng soil samples except R0. The results from functional diversity suggested that the microbial metabolic diversity of fallow soil abandoned in 2003 was the maximum and transplanted soil was higher than direct-seeding soil and the forest soil uncultivated P. ginseng, whereas the increase in cultivation ages in the same mode led to decreases in microbial diversity in P. ginseng soil. Carbohydrates, amino acids, and polymers were the main carbon sources utilized. Furthermore, the microbial diversity index and multivariate comparisons indicated that the augmentation of P. ginseng cultivation ages resulted in decreased bacterial diversity and increased fungal diversity, whereas microbial diversity was improved strikingly in transplanted soil and fallow soil abandoned for at least one decade. CONCLUSION: The key factors for discontinuous P. ginseng cultivation were the lack of balance in rhizosphere microbial communities and the outbreak of soilborne diseases caused by the accumulation of its root exudates. PMID- 26843820 TI - Optimal fertilizer application for Panax notoginseng and effect of soil water on root rot disease and saponin contents. AB - BACKGROUND: Blind and excessive application of fertilizers was found during the cultivation of Panax notoginseng in fields, as well as increase in root rot disease incidence. METHODS: Both "3414" application and orthogonal test designs were performed at Shilin county, Yunnan province, China, for NPK (nitrogen, phosphorus, and potassium) and mineral fertilizers, respectively. The data were used to construct the one-, two-, and three-factor quadratic regression models. The effect of fertilizer deficiency on root yield loss was also analyzed to confirm the result predicted by these models. A pot culture experiment was performed to observe the incidence rate of root rot disease and to obtain the best range in which the highest yield of root and saponins could be realized. RESULTS: The best application strategy for NPK fertilizer was 0 kg/667 m(2), 17.01 kg/667 m(2), and 56.87 kg/667 m(2), respectively, which can produce the highest root yield of 1,861.90 g (dried root of 100 plants). For mineral fertilizers, calcium and magnesium fertilizers had a significant and positive effect on root yield and the content of four active saponins, respectively. The severity of root rot disease increased with the increase in soil moisture. The best range of soil moisture varied from 0.56 FC (field capacity of water) to 0.59 FC, when the highest yield of root and saponins could be realized as well as the lower incidence rate of root disease. CONCLUSION: These results indicate that the amount of nitrogen fertilizer used in these fields is excessive and that of potassium fertilizer is deficient. Higher soil moisture is an important factor that increases the severity of the root rot disease. PMID- 26843814 TI - Vitamin D and the Promotion of Long-Term Metabolic Health from a Programming Perspective. AB - Studies linking vitamin D and long-term metabolic health have generated much debate. Recommendations for the intake of vitamin D by the general public and by the health care professionals have been complicated by a number of inconsistencies in the literature. These caveats relate to the methodological approaches, differences in the populations (and the species) of study, and the definitions used for thresholds of vitamin D status. This review addresses current evidence available for assessing the potential programming of long-term metabolic health of offspring by maternal vitamin D status in pregnancy. It summarizes knowledge on the early origins of metabolic health and analyzes evidence for an association between the vitamin D status in pregnancy and maternal and fetal health status. In addition, we analyze the link between the regulation of inflammation and the vitamin D status in the general population to inform on the general mechanisms through which early vitamin D might affect the programming of long-term health. The evidence suggests an association between the vitamin D status in early life and the programming of long-term health. However, to the best of our knowledge, the current finding is insufficient to draw a final conclusion for evidence-based preventive actions. The data warrant replication in prospective studies and additional research substantiating the causal factors and pathways. PMID- 26843821 TI - Alteration of Panax ginseng saponin composition by overexpression and RNA interference of the protopanaxadiol 6-hydroxylase gene (CYP716A53v2). AB - BACKGROUND: The roots of Panax ginseng contain noble tetracyclic triterpenoid saponins derived from dammarenediol-II. Dammarene-type ginsenosides are classified into the protopanaxadiol (PPD) and protopanaxatriol (PPT) groups based on their triterpene aglycone structures. Two cytochrome P450 (CYP) genes (CYP716A47 and CYP716A53v2) are critical for the production of PPD and PPT aglycones, respectively. CYP716A53v2 is a protopanaxadiol 6-hydroxylase that catalyzes PPT production from PPD in P. ginseng. METHODS: We constructed transgenic P. ginseng lines overexpressing or silencing (via RNA interference) the CYP716A53v2 gene and analyzed changes in their ginsenoside profiles. RESULT: Overexpression of CYP716A53v2 led to increased accumulation of CYP716A53v2 mRNA in all transgenic roots compared to nontransgenic roots. Conversely, silencing of CYP716A53v2 mRNA in RNAi transgenic roots resulted in reduced CYP716A53v2 transcription. HPLC analysis revealed that transgenic roots overexpressing CYP716A53v2 contained higher levels of PPT-group ginsenosides (Rg1, Re, and Rf) but lower levels of PPD-group ginsenosides (Rb1, Rc, Rb2, and Rd). By contrast, RNAi transgenic roots contained lower levels of PPT-group compounds and higher levels of PPD-group compounds. CONCLUSION: The production of PPD- and PPT-group ginsenosides can be altered by changing the expression of CYP716A53v2 in transgenic P. ginseng. The biological activities of PPD-group ginsenosides are known to differ from those of the PPT group. Thus, increasing or decreasing the levels of PPT-group ginsenosides in transgenic P. ginseng may yield new medicinal uses for transgenic P. ginseng. PMID- 26843822 TI - Hippocampus-dependent cognitive enhancement induced by systemic gintonin administration. AB - BACKGROUND: A number of neurological and neurodegenerative diseases share impaired cognition as a common symptom. Therefore, the development of clinically applicable therapies to enhance cognition has yielded significant interest. Previously, we have shown that activation of lysophosphatidic acid receptors (LPARs) via gintonin application potentiates synaptic transmission by the blockade of K(+) channels in the mature hippocampus. However, whether gintonin may exert any beneficial impact directly on cognition at the neural circuitry level and the behavioral level has not been investigated. METHODS: In the current study, we took advantage of gintonin, a novel LPAR agonist, to investigate the effect of gintonin-mediated LPAR activation on cognitive performances. Hippocampus-dependent fear memory test, synaptic plasticity in the hippocampal brain slices, and quantitative analysis on synaptic plasticity-related proteins were used. RESULTS: Daily oral administration of gintonin for 1 wk significantly improved fear memory retention in the contextual fear-conditioning test in mice. We also found that oral administration of gintonin for 1 wk increased the expression of learning and memory-related proteins such as phosphorylated cyclic adenosine monophosphate-response element binding (CREB) protein and brain-derived neurotrophic factor (BDNF). In addition, prolonged gintonin administration enhanced long-term potentiation in the hippocampus. CONCLUSION: Our observations suggest that the systemic gintonin administration could successfully improve contextual memory formation at the molecular and synaptic levels as well as the behavioral level. Therefore, oral administration of gintonin may serve as an effective noninvasive, nonsurgical method of enhancing cognitive functions. PMID- 26843823 TI - Increase in apoptotic effect of Panax ginseng by microwave processing in human prostate cancer cells: in vitro and in vivo studies. AB - BACKGROUND: Ginseng, which is widely used in functional foods and as an herbal medicine, has been reported to reduce the proliferation of prostate cancer cells by mechanisms that are not yet fully understood. METHODS: This study was designed to investigate the changes in ginsenoside content in ginseng after treatment with a microwave-irradiation thermal process and to verify the anticancer effects of the extracts. To confirm the anticancer effect of microwave-irradiated processed ginseng (MG), it was tested in three human prostate cancer cell lines (DU145, LNCaP, and PC-3 cells). Involvements of apoptosis and autophagy were assessed using Western blotting. RESULTS: After microwave treatment, the content of ginsenosides Rg1, Re, Rb1, Rc, Rb2, and Rd in the extracts decreased, whereas the content of ginsenosides 20(S)-Rg3, 20(R)-Rg3, Rk1, and Rg5 increased. Antiproliferation results for the human cancer cell lines treated with ginseng extracts indicate that PC-3 cells treated with MG showed the highest activity with an half maximal inhibitory concentration of 48 MUg/mL. We also showed that MG suppresses the growth of human prostate cancer cell xenografts in athymic nude mice as an in vivo model. This growth suppression by MG is associated with the inductions of cell death and autophagy. CONCLUSION: Therefore, heat processing by microwave irradiation is a useful method to enhance the anticancer effect of ginseng by increasing the content of ginsenosides Rg3, Rg5, and Rk1. PMID- 26843824 TI - Comparative phenolic compound profiles and antioxidative activity of the fruit, leaves, and roots of Korean ginseng (Panax ginseng Meyer) according to cultivation years. AB - BACKGROUND: The study of phenolic compounds profiles and antioxidative activity in ginseng fruit, leaves, and roots with respect to cultivation years, and has been little reported to date. Hence, this study examined the phenolic compounds profiles and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free-radical-scavenging activities in the fruit, leaves, and roots of Korean ginseng (Panax ginseng Meyer) as a function of cultivation year. METHODS: Profiling of 23 phenolic compounds in ginseng fruit, leaves, and roots was investigated using ultra-high performance liquid chromatography with the external calibration method. Antioxidative activity of ginseng fruit, leaves, and roots were evaluated using the method of DPPH free-radical-scavenging activity. RESULTS: The total phenol content in ginseng fruit and leaves was higher than in ginseng roots (p < 0.05), and the phenol content in the ginseng samples was significantly correlated to the DPPH free-radical-scavenging activity (r = 0.928****). In particular, p-coumaric acid (r = 0.847****) and ferulic acid (r = 0.742****) greatly affected the DPPH activity. Among the 23 phenolic compounds studied, phenolic acids were more abundant in ginseng fruit, leaves, and roots than the flavonoids and other compounds (p < 0.05). In particular, chlorogenic acid, gentisic acid, p- and m coumaric acid, and rutin were the major phenolic compounds in 3-6-yr-old ginseng fruit, leaves, and roots. CONCLUSION: This study provides basic information about the antioxidative activity and phenolic compounds profiles in fruit, leaves, and roots of Korean ginseng with cultivation years. This information is potentially useful to ginseng growers and industries involved in the production of high quality and nutritional ginseng products. PMID- 26843825 TI - Total saponin from Korean Red Ginseng inhibits binding of adhesive proteins to glycoprotein IIb/IIIa via phosphorylation of VASP (Ser(157)) and dephosphorylation of PI3K and Akt. AB - BACKGROUND: Binding of adhesive proteins (i.e., fibrinogen, fibronectin, vitronectin) to platelet integrin glycoprotein IIb/IIIa (alphaIIb/beta3) by various agonists (thrombin, collagen, adenosine diphosphate) involve in strength of thrombus. This study was carried out to evaluate the antiplatelet effect of total saponin from Korean Red Ginseng (KRG-TS) by investigating whether KRG-TS inhibits thrombin-induced binding of fibrinogen and fibronectin to alphaIIb/beta3. METHODS: We investigated the effect of KRG-TS on phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and dephosphorylation of phosphatidylinositol 3-kinase (PI3K) and Akt, affecting binding of fibrinogen and fibronectin to alphaIIb/beta3, and clot retraction. RESULTS: KRG-TS had an antiplatelet effect by inhibiting the binding of fibrinogen and fibronectin to alphaIIb/beta3 via phosphorylation of VASP (Ser(157)), and dephosphorylation of PI3K and Akt on thrombin-induced platelet aggregation. Moreover, A-kinase inhibitor Rp-8-Br-cyclic adenosine monophosphates (cAMPs) reduced KRG-TS increased VASP (Ser(157)) phosphorylation, and increased KRG-TS-inhibited fibrinogen-, and fibronectin-binding to alphaIIb/beta3. These findings indicate that KRG-TS interferes with the binding of fibrinogen and fibronectin to alphaIIb/beta3 via cAMP-dependent phosphorylation of VASP (Ser(157)). In addition, KRG-TS decreased the rate of clot retraction, reflecting inhibition of alphaIIb/beta3 activation. In this study, we clarified ginsenoside Ro (G-Ro) in KRG-TS inhibited thrombin-induced platelet aggregation via both inhibition of [Ca(2+)]i mobilization and increase of cAMP production. CONCLUSION: These results strongly indicate that KRG-TS is a beneficial herbal substance inhibiting fibrinogen-, and fibronectin-binding to alphaIIb/beta3, and clot retraction, and may prevent platelet alphaIIb/beta3-mediated thrombotic disease. In addition, we demonstrate that G-Ro is a novel compound with antiplatelet characteristics of KRG-TS. PMID- 26843826 TI - Changes in the contents of prosapogenin in Red ginseng (Panax ginseng) depending on the extracting conditions. AB - This study compared the contents of prosapogenin depending on the extracting conditions of Red ginseng to provide basic information for developing Red ginseng based functional foods. The content of ginsenoside Rg3 reached their maximum value at 24 h of extraction, followed by 36 h and 72 h of extraction at 100 degrees C. PMID- 26843827 TI - Assessment of microclimate conditions under artificial shades in a ginseng field. AB - BACKGROUND: Knowledge on microclimate conditions under artificial shades in a ginseng field would facilitate climate-aware management of ginseng production. METHODS: Weather data were measured under the shade and outside the shade at two fields located in Gochang-gun and Jeongeup-si, Korea, in 2011 and 2012 seasons to assess temperature and humidity conditions under the shade. An empirical approach was developed and validated for the estimation of leaf wetness duration (LWD) using weather measurements outside the shade as inputs to the model. RESULTS: Air temperature and relative humidity were similar between under the shade and outside the shade. For example, temperature conditions favorable for ginseng growth, e.g., between 8 degrees C and 27 degrees C, occurred slightly less frequently in hours during night times under the shade (91%) than outside (92%). Humidity conditions favorable for development of a foliar disease, e.g., relative humidity > 70%, occurred slightly more frequently under the shade (84%) than outside (82%). Effectiveness of correction schemes to an empirical LWD model differed by rainfall conditions for the estimation of LWD under the shade using weather measurements outside the shade as inputs to the model. During dew eligible days, a correction scheme to an empirical LWD model was slightly effective (10%) in reducing estimation errors under the shade. However, another correction approach during rainfall eligible days reduced errors of LWD estimation by 17%. CONCLUSION: Weather measurements outside the shade and LWD estimates derived from these measurements would be useful as inputs for decision support systems to predict ginseng growth and disease development. PMID- 26843828 TI - Phylogenetic placement of the unusual jumping spider Depreissia Lessert, and a new synapomorphy uniting Hisponinae and Salticinae (Araneae, Salticidae). AB - The relationships of the unusual salticid spider Depreissia from central Africa and Borneo have been difficult to resolve, obscured by its highly modified ant like body. Phylogenetic analysis of the gene 28S strongly supports its placement outside the major clade Salticinae and within the clade of cocalodines, spartaeines and lapsiines, with weaker support for a relationship with the cocalodines in particular. Excluding the genus from the Salticinae is supported also by the presence of a median apophysis on the male palp, and by the lack of a cymbial apical groove cradling the tip of embolus, which is newly presented here as a synapomorphy of Hisponinae plus Salticinae. PMID- 26843829 TI - Review of the genus Laelaspisella Marais & Loots, with the description of a new species from Iran (Acari, Laelapidae). AB - A new species of mite is described from Iran, Laelaspisella elsae sp. n. (Acari: Laelapidae). The new species was collected from bark of elm trees in Isfahan province. A revised diagnosis for Laelaspisella, as well as a key to the world species of the genus, are presented. Two species groups of Laelaspisella are proposed: those with seta pd3 on genu I and those without pd3 on genu I. Pseudoparasitus (Gymnolaelaps) tonsilis Karg, 1989a is transferred to Laelaspisella, based on its hypertrichous holodorsal shield, metasternal setae st4 absent and genu IV with ten setae. The problems with Laelaspisella canestrinii are explained and Laelaspisella canestrinii sensu Berlese (1903), (1904) and Costa (1962) is provided with a new name, Laelaspisella berlesei Joharchi, nom. n. PMID- 26843830 TI - A new genus and species of Laelapidae from Iran with notes on Gymnolaelaps Berlese and Laelaspisella Marais & Loots (Acari, Mesostigmata). AB - Pogonolaelaps gen. n. a new genus of Laelapidae Berlese is erected and described based on Pogonolaelaps canestrinii (Berlese), comb. n. as well as on specimens which were collected from soil and ant nests in different parts of Iran. Also, a new species Pogonolaelaps beaulieui sp. n. is described based on specimens collected from soil, litter and ant nests in various parts of Chaharmahal va Bakhtiari province, Iran. The genus Gymnolaelaps is revised considering species with some morphological deviations. Gymnolaelaps reniculus (Karg, 1981) and Gymnolaelaps triquetrus (Karg, 2003) are removed from this genus and placed in their original genus Pseudoparasitus. The characters of Laelaspisella Marais & Loots, 1969 are discussed in a detail along with a proposal of a new definition. PMID- 26843831 TI - Mysmenidae, a spider family newly recorded from Tibet (Arachnida, Araneae). AB - The spider family Mysmenidae is reported from Tibet for the first time. Two new species, Chanea voluta sp. n. (male and female) and Mysmena lulanga sp. n. (male and female) are found in eastern Tibet in high altitude. Morphological descriptions, diagnoses and comparative photos are provided for the two new species. PMID- 26843832 TI - Thysanoptera-Terebrantia of the Hawaiian Islands: an identification manual. AB - An illustrated identification system is presented to 99 species and 49 genera in three families recorded from the Hawaiian Islands in the Thysanoptera suborder Terebrantia. Only seven (possibly eight) of these species are considered endemic, the remainder being adventive to these islands. The only previous study of Hawaiian Thysanoptera, by Zimmerman in 1948, included 47 Terebrantia species in 21 genera. PMID- 26843833 TI - A new species of Docosia Winnertz from Central Europe, with DNA barcoding based on four gene markers (Diptera, Mycetophilidae). AB - A new species of Docosia Winnertz, Docosia dentata sp. n., is described and illustrated, based on a single male specimen collected in Muranska planina National Park in Central Slovakia. DNA sequences (COI, COII, CytB, and ITS2) are included and compared for 13 species of Docosia. There was found only little congruence between the molecular results and previous scarce data about interspecific relationships based on morphology. The COI and CytB gene markers showed the highest interspecific gene distances while ITS2 showed the lowest ones. An updated key to the 23 Central European species of Docosia is also presented. PMID- 26843834 TI - Description of a new species of the genus Laelaspis Berlese (Acari, Mesostigmata, Laelapidae) from Iran. AB - A new species of the genus Laelaspis Berlese, Laelaspis elongatus sp. n. is described based on adult female and male specimens collected in association with Pheidole pallidula (Nylander) (Hym., Formicidae) in Ahwaz, Khuzestan Province, southwestern Iran, and also Acinopus (Acinopus) picipes (Olivier) (Col., Carabidae) in Bam, Kerman Province, southeastern Iran. PMID- 26843835 TI - Characteristics and Patterns of Metastatic Disease from Chordoma. AB - Chordoma is a rare, slow-growing malignant tumor arising from notochordal remnants. A retrospective review of patient records at two major referral centers was undertaken to assess the incidence, location, and prognostic factors of metastatic disease from chordoma. 219 patients with chordoma (1962-2009) were identified. 39 patients (17.8%) developed metastatic disease, most frequently to lung (>50%). Median survival from the time of initial diagnosis was 130.4 months for patients who developed metastatic disease and 159.3 months for those who did not (P = 0.05). Metastatic disease was most common in the youngest patients (P = 0.07), and it was 2.5 times more frequent among patients with local recurrence (26.3%) than in those without (10.8%) (P = 0.003). Patient survival with metastatic disease was highly variable, and it was dependent on both the location of the tumor primary and the site of metastasis. Metastasis to distal bone was the most rapid to develop and had the worst prognosis. PMID- 26843836 TI - Role of microRNAs in the resistance of prostate cancer to docetaxel and paclitaxel. AB - Taxanes, a group of cancer drugs that includes docetaxel and paclitaxel, have become a front-line therapy for a variety of metastatic cancers, but resistance can develop. There are several docetaxel resistance mechanisms in prostate cancer: unfavorable tumor microenvironment, drug efflux pump, alterations in microtubule structure and/or function, and apoptotic defects (e.g. up regulation of Bcl-2 and clusterin or activation of the PTEN/PI3K/mTOR pathway or activation of the MAPK/ERK pathway). MicroRNAs (miRNAs), small regulatory molecules, could also function as a contributor to the resistance of cancer cells to commonly used anti-cancer drugs. Aberrant expressions of miRNAs that can act as tumor suppressors or oncogenes are closely associated with the development, invasion and metastasis of various cancers including prostate cancer. Nearly 50 miRNAs have been reported to be differentially expressed in human prostate cancer so far, but knowledge concerning the effects of miRNAs on the sensitivity to anti cancer drugs is still limited. The author of the review focus on probable impact of miRNAs on the resistance to docetaxel and paclitaxel. Overexpression of miR-21 increased the resistance of prostate cancer cells to docetaxel by targeting PDCD4, PTEN, RECK, and BTG2. Nevertheless, decreased expressions of tumor suppressors: miR-34a, miR-143, miR-148a and miR-200 family are involved in resistance of anti-cancer drugs by inhibition of apoptosis and activation of signaling pathways. Conclude miRNAs become very attractive target for potential therapeutic interventions. PMID- 26843837 TI - Current trends in the treatment of primary mediastinal large B-cell lymphoma - an overview. AB - Primary mediastinal large B-cell lymphoma has been recognised as a distinct entity with unique clinical, pathologic, and genetic features. According to WHO 2008 classification it is marked as a variant of diffuse large B-cell lymphoma but shares characteristics with classic Hodgkin lymphoma. Genetic analysis has shown that amplification of the 9p24.1 region is the disease's specific structural alteration. Aggressive behaviour and a tendency to invade surrounding tissues of the thoracic cavity, often causing superior vena cava syndrome, or pleural or pericardial effusions, are the clinical hallmarks of this disease. For a long period of time it has been considered as a disease with poor prognosis, which responds poorly to the conventional treatment created for diffuse large B cell lymphoma. An elective treatment has not yet been established, but recently the situation has became much more favourable. After the introduction of rituximab the cure rates have risen to over 80%, and the most recent results have demonstrated a new insight with dose-adjusted intensified continuous treatments, in which the cure rates have exceeded 90%. Current trends have led to the introduction of dose-adjusted intensified protocols becoming a standard of care, whereas the use of radiotherapy remains controversial because of the questionable predictive value of post-treatment PET/CT validity. The relapse rate is very low after two years of sustained complete remission. If the disease relapses or is resistant the outcome is very poor regardless of the applied treatment modality. PMID- 26843838 TI - Potential use of histone deacetylase inhibitors in cancer therapy. AB - Epigenetics is a branch of science that focuses on mechanisms related to control and modification of expression of genetic material without any changes to its sequences. Such mechanisms include post-translational modifications of histones. It is widely known that carcinogenesis is related to hypoacetylation of genes that influence apoptosis, the cell cycle, cell signaling, the immunologic response, angiogenesis and occurrence of metastasis. Currently conducted research focuses on several strategies related to epigenetic therapy. One such strategy is based on the use of histone deacetylase inhibitors. This paper presents mechanisms through which these compounds work and a summary of their characteristics. It also includes a review of clinical tests related to histone deacetylase inhibitors, as well as their relationship with other chemotherapeutic methods. A better understanding of the involved mechanisms will provide a rational basis to improve the therapeutic outcome of available antitumor agents. PMID- 26843839 TI - Complement factor H polymorphism rs1061170 and the effect of cigarette smoking on the risk of lung cancer. AB - AIM OF THE STUDY: Complement factor H (CFH) has been known to inhibit the complement pathway and to contribute to tumour growth by suppressing the anti tumour cell mediated response in cell lines from several malignancies. We examined the association of Try402His single nucleotide polymorphism in CFH gene with lung cancer and the interaction with cigarette smoking. MATERIAL AND METHODS: This case-control study included 80 primary lung cancer patients and 106 control subjects who were genotyped for Try402His (rs1061170) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Variant genotypes (Tyr/His and His/His) were overpresented among patients compared to controls (p = 0.03, OR = 2.510, 95% CI: 1.068-5.899), and the frequency of variant H allele was significantly overexpressed in cases compared to controls (p = 0.021). Tyr/His genotype was identified in 100% of small cell lung cancer (SCLC) patients vs. 34.5% of non-SCLC (NSCLC), while 20.7% of NSCLC patients were homozygous for the variant allele (His/His) (p = 0.001). Binary logistic regression analysis revealed a 2.5 times greater estimated risk for NSCLC than for SCLC among variant allele carriers, and a 7.3-fold increased risk of lung cancer among variant allele smoking carriers vs. 1.3-fold increased risk among wild allele smoking carriers. Moreover, the stage of cancer positively correlated with smoking and pack-years in allele H carriers, and the correlation was stronger among those who were homozygous for it (His/His) than those who were heterozygous (Tyr/His). CONCLUSIONS: CFH 402H variant is a smoking-related risk factor for lung cancer, particularly the NSCLC. PMID- 26843840 TI - VEGF-C expression is not a prognostic factor in locally advanced colon adenocarcinoma. AB - AIM OF THE STUDY: Evaluation of the relationships between increased expression of VEGF-C (vascular endothelial growth factor-C) and vessel density in the tumour surrounding stroma, patient survival, and other conventional prognostic factors in patients with pT3-4 colon cancer. MATERIAL AND METHODS: Expression of VEGF-C and vessel density were immunohistochemically assessed in 104 specimens of primary, locally advanced (pT3-4) colon adenocarcinoma after surgical resection. RESULTS: A significant relationship was found between the expression of VEGF-C and increased vessel density in the tumour-surrounding stroma (p = 0.03). A relationship between VEGF-C expression and location of the tumour in the left side of the colon was also found (p = 0.003). Expression of VEGF-C was likely to occur in well-differentiated tumours. No relationship between patient overall survival and the expression level of VEGF-C in locally advanced colon cancer was observed. CONCLUSIONS: The study results indicate that expression of VEGF-C in cells of locally advanced pT3-4 adenocarcinoma of the colon does not affect the survival time of the patients. Increased expression of VEGF-C is accompanied by a significant increase in vessel density in the pT3-4 tumour stroma. Increased expression of VEGF-C in cancer cells is related to the tumour location in the left side of the colon and better tumour differentiation. PMID- 26843841 TI - Circulating tumour cells predict survival in gastric cancer patients: a meta analysis. AB - AIM OF THE STUDY: The prognostic value of the detection of circulating tumour cells (CTCs) in gastric cancer has been studied intensely in recent years. However, the application of different technologies led to inconsistent results between the studies. Here, we performed a meta-analysis of published studies to summarise the evidence. MATERIAL AND METHODS: Medline and ISI Web of Knowledge were searched up to March 2013 using "circulating tumor cells" and "gastric cancer" as search terms. Hazard ratio (HR) with 95% confidence intervals (CIs) for prognostic outcomes and clinical characteristics were extracted from each study. Pooled hazard ratios (HR) and odds ratios (OR) were calculated using random or fixed-effects models. RESULTS: Twelve studies enrolling 774 patients were included. The combined HR estimate for overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS) were 1.41 (95% CI: 1.28 1.62), 2.99 (95% CI: 2.01-4.45) and 1.64 (95% CI: 1.02-2.62), respectively. Subgroup analysis concerning detection methods and sampling time showed that results of RT-PCR for the OS group and RT-PCR for the DFS group suggest a prognostic significance of CTC detection (pooled HR [95% CI]: 1.45 [1.28-1.65], I(2) = 38%, p = 0.13; 2.99 [2.01-4.45], I(2) = 0%, p = 0.32). In addition, results of the baseline CTC detection group also indicated a significant prognostic value to predict OS and DFS (pooled HR [95% CI]: 1.47 [1.19-1.82], I(2) = 38%, p = 0.14; 2.99 [2.01-4.45], I(2) = 0%, p = 0.32). We simultaneously found that the detection of CTCs correlated with pathological stage (pooled OR [95% CI]: 2.95 [1.65-5.28], I(2) = 56%, p = 0.03), lymph node status (pooled OR [95% CI]: 2.26 [1.50-3.41], I(2) = 37%, p = 0.09), the depth of invasion (pooled OR [95% CI]: 3.21 [1.38-7.43], I(2) = 72%, p = 0.002), and distant metastasis (pooled OR [95% CI]: 2.68 [1.25-5.73], I(2) = 43%, p = 0.15). CONCLUSIONS: Detection of CTCs is associated with poorer prognosis in gastric cancer patients. PMID- 26843842 TI - Less aggressive disease in patients with primary squamous cell carcinomas of the thyroid gland and coexisting lymphocytic thyroiditis. AB - AIM OF THE STUDY: Primary squamous cell carcinoma (SCC) of the thyroid gland is extremely rare. Infrequently, primary SCC of the thyroid gland is accompanied by other thyroid diseases such as Hashimoto's thyroiditis (HT). Recently, studies have demonstrated that differentiated thyroid cancer with coexisting HT has a better prognosis. However, the prognosis of patients with primary SCC of the thyroid gland and coexistent HT has not been clearly identified. We compared the clinical characteristics and disease stages of patients with primary SCC with and without lymphocytic thyroiditis (LT). MATERIAL AND METHODS: We reviewed reports of primary SCC of the thyroid gland published in the English literature. RESULTS AND CONCLUSIONS: We identified 46 papers that included 17 cases of primary SCC of the thyroid gland with LT and 77 cases of primary SCC of the thyroid gland without LT. Lymph node metastasis and local invasion rates did not differ between these two groups. Distant metastases were absent in patients with LT, and were observed in 13 (16.9%) patients without LT. A greater proportion of patients without LT had advanced stage disease (stage IV A-B-C) than patients with LT (p < 0.05). Patients with primary SCC of the thyroid gland and coexisting LT had lower tumour-node-metastasis stage and frequency of distant metastasis than those without LT. Lymphocytic infiltration in patients with SCC appears to limit tumour growth and distant metastases. PMID- 26843843 TI - The association of subtypes of breast cancer with tumour characteristics and reproductive factors in 1326 Mexican women. AB - AIM OF THE STUDY: In breast cancer, oestrogen receptor (ER), progesterone receptor (PgR), and HER2 (HER2/Neu) expression status are used to classify neoplasms into subtypes: Luminal A, Luminal B, HER2/Neu type, and Basallike. The aim of the present study was to establish the molecular subtypes of breast cancers and their association with tumour characteristics and reproductive factors in Mexican women. MATERIAL AND METHODS: A total of 1326 biopsies of breast tumour tissues were analysed for ER, PR, and HER2/Neu by immunohistochemistry (IHC). Information regarding age, tumour characteristics, and node involvement profiles were collected. RESULTS: IHC established that the most common subtype of breast cancer was Luminal A (64.93%), followed by Basal Like (13.88%), Luminal B (12.52%), and HER2/Neu (8.67%). T2-size tumours (> 2 cm but < 5 cm) were present in 47.59% of all patients. Univariate analysis showed that lymph node positivity (p = 0.009), stage (p = 0.013), and placement of the tumour (p = 0.001) were factors associated with breast cancer subtype. CONCLUSIONS: Our data show that IHC is useful for distinguishing different subtypes of breast cancer and that Luminal A is the most common breast cancer subtype in the Mexican population. All subtypes were associated with unfavourable clinicopathological features, suggesting that late diagnosis is an important contributor to high mortality rates in the Mexican population. PMID- 26843844 TI - Azacitidine in outpatient treatment - single center experience. AB - AIM OF THE STUDY: Azacitidine is a hypomethylating agent which is used in the treatment of myelodysplastic syndromes, acute myeloid leukemia and chronic myelomonocytic leukemia. Because of good tolerance to the drug, azacitidine can be administered both during hospitalization and in an outpatient setting. The aim of our retrospective analysis was to assess the efficacy of azacitidine treatment in patients with a myelodysplastic syndrome and with acute myeloid leukemia who had received treatment in hospital and in an ambulatory care setting. Offsets in the course of azacitidine administration and discontinuations of treatment have a negative impact on patients' response to the therapy. MATERIAL AND METHODS: The study included 31 patients. Sixteen patients received azacitidine in an ambulatory care setting, 15 patients within their hospitalization. RESULTS: A hematologic response was achieved in 48% of the patients. Forty-one percent of the cycles were delayed. In an outpatient setting, 62% of the cycles were administered systematically, while during hospitalization the patients received 54% of cycles on time. Administrative problems caused the delay of 26% of the cycles. CONCLUSIONS: Azacitidine has a high tolerance level and a high safety profile which allows for its use in an outpatient care setting. Outpatient administration of azacitidine is feasible and safe without compromising efficacy. PMID- 26843845 TI - Gleason score stratification according to age at diagnosis in 1028 men. AB - AIM OF THE STUDY: Gleason score stratification according to age at diagnosis has been retrospectively evaluated in 1028 men with biopsy-proven prostate cancer (PCa). MATERIAL AND METHODS: From January 2006 to December 2014, 2435 Caucasian men aged between 37 and 92 years underwent transperineal prostate biopsy for suspicion of PCa. The indications were as follows: abnormal digital rectal examination (DRE), PSA values > 10 ng/ml or between 4.1-10 or 2.6-4 ng/ml, with free/total PSA < 25% and < 20%, respectively. RESULTS: In 1028 (42.2%) patients with median PSA of 9.6 ng/ml a PCa was found (median age 62.3 years; range: 42-92 years); 757 (73.7%) vs. 271 (26.3%) men had a T1c vs. T2 clinical stage, respectively. Median Gleason score was 7 (range: 6-10). The Gleason score progressively increased with the age of the patients at diagnosis, and a significantly correlation between Gleason score >= 8 and men older than 80 years was demonstrated (p = 0.0001). CONCLUSIONS: The detection rate of aggressiveness of PCa progressively increased with the age at diagnosis; Gleason score >= 8 was more frequently diagnosed in men older than 80 years with PSA values > 10 ng/ml (about 80% of the cases) and abnormal DRE (about 60% of the cases). PMID- 26843846 TI - An analysis of malignant tumour incidence in the male population of Poland in the period 2006-2010. AB - In the period 2006-2010, the National Cancer Registry indicated a gradual increase in the incidence of malignant tumours among men, from 64,092 thousand in 2006 to 70,024 thousand in 2010. In the reference period, the number of deaths due to malignant tumours among men oscillated around 52 thousand. The aim of this study was to analyse the incidence of malignant tumours in the male population of Poland in the period 2006-2010. The study material comprised data obtained from the National Cancer Registry and from the Central Statistical Office, available on the websites of these institutions. The malignant-tumour incidence rate among the male population in 2006-2010 showed a slow but steady growth, while the death rate dropped slightly at the end of 2010. The hypothesis that the cancer incidence risk grows with age has been proven, and a substantial increase in this risk is observed from the fourth decade of life. The most common malignant tumours in Poland in the analysed period included lung cancer, followed by prostate cancer and colorectal cancer. Future prophylactic and educational programmes should be addressed to men prior to reaching the age of increased cancer risk. PMID- 26843847 TI - Cost-effectiveness analysis of lung cancer screening with low-dose computerised tomography of the chest in Poland. AB - AIM OF THE STUDY: To determine the cost-effectiveness of lung cancer (LC) screening with low-dose computerised tomography of the chest, as compared to an approach without screening, reimbursed today by the National Health Fund (NHF) in Poland. MATERIAL AND METHODS: In order to analyse the current costs of diagnostic and therapeutic procedures of a model LC patient treated today, a model group consisting of 199 consecutive patients diagnosed and treated in the Oncology Centre in Bydgoszcz, Poland from January 2007 to April 2010 was used. The number and type of performed procedures in this group was obtained from the Polish Register of Neoplasms and the NHF. Only direct medical costs were analysed. To calculate the total costs of screening, diagnostics, and treatment of the hypothetical LC patient who would have cancer diagnosed with screening CT, data from the literature and costs calculated for the model group were used. Prices of procedures were obtained from the price list of the NHF on 30 April 2010 and did not change from that time until June 2014. One-way sensitivity analysis was performed. RESULTS: The average cost per LC patient, diagnosed and treated without screening, is 5567.50 EUR, and median LC-specific survival is one year. In the hypothetical LC patient with cancer diagnosed by screening, the average cost is 13689.35 EUR per LC patient, with a median LC-specific survival of at least seven years. A calculated incremental cost-effectiveness ratio (ICER) is 1353.64 EUR/year of life gained. CONCLUSIONS: Lung cancer screening with low-dose CT would be highly cost-effective in Poland. PMID- 26843848 TI - Perception and awareness of patients regarding ovarian cysts in Peshawar, Pakistan: a qualitative approach. AB - AIM OF THE STUDY: Women health is one of the key issues in developing countries including Pakistan. To improve the women's quality of life, awareness about health is necessary. The objective of this study is to evaluate the patient's perception regarding ovarian cyst and the awareness of the patients about the symptoms and health management in ovarian cyst. MATERIAL AND METHODS: A qualitative approach was used to conduct this study. An interview guide was prepared for the data collection. The interview guide had 29 questions which were asked from the patients. The duration of each interview was about 15-20 minutes and conducted in native language (Urdu) which was then translated to English language for the purpose of documentation. Snowball technique was adopted and the sample size was estimated from the point of saturation. RESULTS: All the interviews were conducted in the Gynecology ward of Hayatabad Medical Complex (HMC), Peshawar, Pakistan. Results were thematically analyzed. Thematic content analysis yielded 5 major themes: 1) Irregular menstrual cycle, 2) nausea and vomiting, 3) difficulty in emptying urinary bladder completely, 4) emergency due to severe pain, and 5) Physical works. CONCLUSIONS: There is a need of time that patients should be counseled at the time of discharge of the patient from the hospital. This is the right of the patient that they know about their disease and benefits of the successful treatment outcomes. Compliance can only be achieved through the counseling of the patients, resulting good quality of life and less economic burden over the patients. PMID- 26843849 TI - Dejection and self-assessment of quality of life in patients with lung cancer subjected to palliative care. AB - AIM OF THE STUDY: To evaluate the intensity of dejection and self-assessment of quality of life in patients with lung cancer from the start of palliative care until death. MATERIAL AND METHODS: The study included 63 patients with lung cancer from the start of care until death in palliative medicine centers in Bydgoszcz in 2012-2013. The visual-analogue scale constituting part of the ESAS scale was used to assess dejection, while question number 30 of the EORTC QLQ-C30 was used for self-assessment of quality of life. RESULTS: "Moderate" and "very" intense dejection initially occurred in 19 (30%) and 24 (38%), and in the 2(nd) assessment in as many as 23 (36%) and 30 (48%) patients. Average quality of life deteriorated in this respect by 0.09 in the two-step scale (p = 0.005). Increase in the intensity of "moderate" dejection occurred between the 1(st) and 3(rd) assessment. Initially it occurred in 2 (9%) patients and in 14 (66%) during the 3(rd) assessment. In contrast, the levels of "very" severe dejection did not change significantly between the 1(st) and the 3(rd) assessment. The average quality of life deteriorated by 0.23 points (p = 0.004). A significant relationship was found only between analgesic treatment and quality of life (p < 0.0005). Other factors such as age, time from diagnosis to start of treatment, place of residence, sex, or financial condition did not affect the quality of life. CONCLUSIONS: Self-assessment of the quality of life worsens with time. The intensity of dejection does not change in the last 3 weeks of life. In multivariate analysis, among the selected variables such as age, sex, place of residence, time from diagnosis to start of palliative care, financial condition, and type of painkillers used, only the latter has an impact on self-assessed quality of life. PMID- 26843850 TI - Quantitative succinylome analysis in the liver of non-alcoholic fatty liver disease rat model. AB - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a clinical frequent disease. However, its pathogenesis still needs further study, especially the mechanism at the molecular level. The recent identified novel protein post translational modification, lysine succinylation was reported involved in diverse metabolism and cellular processes. In this study, we performed the quantitative succinylome analysis in the liver of NAFLD model to elucidate the regulatory role of lysine succinylation in NAFLD progression. METHODS: Firstly, experimental model of NAFLD was induced by carbon tetrachloride injection and supplementary high-lipid and low-protein diet. Then series histochemical and biochemical variables were determined. For the quantitative succinylome analysis, tandem mass tags (TMT)-labeling, highly sensitive immune-affinity purification, liquid chromatography-tandem mass spectrometry techniques were applied. Bioinformatics analysis including gene ontology annotation based classification; Wolfpsort based subcellular prediction; function enrichment; protein-protein interaction network construction and conserved succinylation site motifs extraction were performed to decipher the differentially changed succinylated proteins and sites and p-value < 0.05 was selected as threshold. RESULTS: Totally, 815 succinylation sites on 407 proteins were identified, of which 243 succinylation acetylation sites on 178 proteins showed changed succinylation level with the threshold fold change > 1.5. Theses differentially changed succinylated proteins were involved in diverse metabolism pathways and cellular processes including carbon metabolism, amino acid metabolism, fat acid metabolism, binding and catalyzing, anti-oxidation and xenobiotics metabolism. Besides, these differentially changed succinylated proteins were prominently localized to cytoplasm and mitochondria. Moreover, 8 conserved succinylation site motifs were extracted around the succinylation sites. CONCLUSIONS: Protein succinylation was an extensive post-translation modification in rat. The changed succinylation level in diverse proteins may disturb multiple metabolism pathways and promote non-alcoholic fatty liver disease development. This study provided a basis for further characterization of the pathophysiological role of lysine succinylation in NAFLD progression, which laid a foundation for the innovation of novel NAFLD drugs and therapies. PMID- 26843852 TI - Stability Constants of Mixed Ligand Complexes of Nickel(II) with Adenine and Some Amino Acids. AB - Nickel is one of the essential trace elements found in biological systems. It is mostly found in nickel-based enzymes as an essential cofactor. It forms coordination complexes with amino acids within enzymes. Nickel is also present in nucleic acids, though its function in DNA or RNA is still not clearly understood. In this study, complex formation tendencies of Ni(II) with adenine and certain L amino acids such as aspartic acid, glutamic acid, asparagine, leucine, phenylalanine, and tryptophan were investigated in an aqueous medium. Potentiometric equilibrium measurements showed that both binary and ternary complexes of Ni(II) form with adenine and the above-mentioned L-amino acids. Ternary complexes of Ni(II)-adenine-L-amino acids are formed by stepwise mechanisms. Relative stabilities of the ternary complexes are compared with those of the corresponding binary complexes in terms of Deltalog10?K, log10?X, and % RS values. It was shown that the most stable ternary complex is Ni(II):Ade:L-Asn while the weakest one is Ni(II):Ade:L-Phe in aqueous solution used in this research. In addition, results of this research clearly show that various binary and ternary type Ni(II) complexes are formed in different concentrations as a function of pH in aqueous solution. PMID- 26843853 TI - A Delphi study for setting up tobacco research and practice network in India. AB - BACKGROUND: There are key gaps in the production and dissemination of evidence based tobacco control research in developing countries. In India, limited research has been made to address and understand the function, constitution, thematic areas of research of a research and practice network in tobacco control. This study aimed to identify priority areas that were agreed by stakeholders for building tobacco research and practice network in India. METHODS: This study used the well-established Delphi survey, which involves asking experts a recurring progression of questions through a series of questionnaires. The study was conducted in two rounds in the year 2013-14. Experts working in tobacco control participated in the study. In Round II, respondents rated agreement using a five point Likert scale. Interquartile Range (IQR) was used to calculate the strength of the consensus. RESULTS: Experts expressed strong consensus on tobacco cessation and economic research as a focus areas for tobacco research network in India. Lack of funding was stated as a barrier impeding formation of tobacco research network in India by majority of respondents. A strong consensus was achieved on the fact that network can be sustained financially by Government funds (IQR = 1). Information sharing and capacity building of young researchers were the two major benefits as stated by respondents which achieved strong consensus. CONCLUSIONS: This study produced the first national stakeholder informed priority area for developing tobacco research and practice network in India. The consensus priorities highlight the most important and urgent needs in developing research and practice network in tobacco control. PMID- 26843854 TI - Non-responders in a quitline evaluation are more likely to be smokers - a drop out and long-term follow-up study of the Swedish National Tobacco Quitline. AB - BACKGROUND: A previous randomized controlled trial (RCT) of the Swedish National Tobacco Quitline detected no significant differences in smoking cessation outcomes between proactive and reactive services at 12-month follow-up. However, the response rate was only 59 % and non-responders were over-represented in the proactive service. We performed a drop-out analysis to assess the smoking status of initial responders and non-responders. METHODS: At 29-48 months after the first call, a postal questionnaire with six questions was sent to 150 random clients from the RCT database, with equal numbers from the proactive and reactive services as well as responders and non-responders at 12-month follow-up. Clients who did not return the questionnaire were contacted by telephone. The outcome measures were point prevalence (PP) and 6-month continuous abstinence (CA), and their associations with response status at 12 months were assessed by logistic regression. RESULTS: The response rate was 74 % (111/150). Abstinence was significantly higher among initial responders than non-responders (PP 54 % vs. 32 %, p = .023 and CA 49 % vs. 21 %, p = .003). The odds ratios for initial responders vs. initial non-responders were, for PP = 2.5 (95 % CI 1.1-5.6, p = .024), and for CA = 3.7 (95 % CI 1.5-8.9, p = .004), after adjusting for proactive/reactive service. CONCLUSIONS: Non-responders to a 12-month follow-up smoking cessation questionnaire in a quitline setting were more likely to be smokers 1.5-3 years later. We propose a conservative correction factor of 0.8 for self-reported abstinence in telephone-based cessation studies if the response rate is approximately 55-65 %. PMID- 26843855 TI - Visual Tracking Based on an Improved Online Multiple Instance Learning Algorithm. AB - An improved online multiple instance learning (IMIL) for a visual tracking algorithm is proposed. In the IMIL algorithm, the importance of each instance contributing to a bag probability is with respect to their probabilities. A selection strategy based on an inner product is presented to choose weak classifier from a classifier pool, which avoids computing instance probabilities and bag probability M times. Furthermore, a feedback strategy is presented to update weak classifiers. In the feedback update strategy, different weights are assigned to the tracking result and template according to the maximum classifier score. Finally, the presented algorithm is compared with other state-of-the-art algorithms. The experimental results demonstrate that the proposed tracking algorithm runs in real-time and is robust to occlusion and appearance changes. PMID- 26843851 TI - Lambda Red-mediated Recombineering in the Attaching and Effacing Pathogen Escherichia albertii. AB - BACKGROUND: The ability to introduce site-specific mutations in bacterial pathogens is essential towards understanding their molecular mechanisms of pathogenicity. This has been greatly facilitated by the genetic engineering technique of recombineering. In recombineering, linear double- or single-stranded DNA molecules with two terminal homology arms are electroporated into hyperrecombinogenic bacteria that express a phage-encoded recombinase. The recombinase catalyzes the replacement of the endogenous allele with the exogenous allele to generate selectable or screenable recombinants. In particular, lambda red recombinase has been instrumental in engineering mutations to characterize the virulence arsenal of the attaching and effacing (A/E) pathogens enteropathogenic Escherichia coli (EPEC), enterohemorrhagic E. coli (EHEC), and Citrobacter rodentium. Escherichia albertii is another member of this taxon; however, the virulence of E. albertii remains cryptic despite accumulating evidence that E. albertii is an emerging pathogen. Multiple retrospective studies have reported that a substantial number of EPEC and EHEC isolates (~15 %) that were previously incriminated in human outbreaks actually belong to the E. albertii lineage. Thus, there is increased urgency to reliably identify and rapidly engineer mutations in E. albertii to systematically characterize its virulence determinants. To the best of our knowledge not a single chromosomal gene has been altered by targeted mutagenesis in E. albertii since it was first isolated almost 25 years ago. This is disconcerting because an E. albertii outbreak could cause significant morbidity and mortality owing to our inadequate understanding of its virulence program. RESULTS: In this report we describe a modified lambda red recombineering protocol to mutagenize E. albertii. As proof of principle, we successfully deleted three distinct virulence-associated genetic loci - ler, grlRA, and hfq - and replaced each wild type allele by a mutant allele with an encodable drug resistance cassette bracketed by FRT sites. Subsequently, the FRT-site flanked drug resistance marker was evicted by FLP dependent site-specific recombination to generate excisants containing a solitary FRT site. CONCLUSIONS: Our protocol will enable researchers to construct marked and unmarked genome-wide mutations in E. albertii, which, in turn, will illuminate its molecular mechanisms of pathogenicity and aid in developing appropriate preventative and therapeutic approaches to combat E. albertii outbreaks. PMID- 26843857 TI - Arginine Vasopressin Injected into the Dorsal Motor Nucleus of the Vagus Inhibits Gastric Motility in Rats. AB - Background. Until now, the effect of arginine vasopressin (AVP) in the DMV on gastric motility and the possible modulating pathway between the DMV and the gastrointestinal system remain poorly understood. Objectives. We aimed to explore the role of AVP in the DMV in regulating gastric motility and the possible central and peripheral pathways. Material and Methods. Firstly, we microinjected different doses of AVP into the DMV and investigated its effects on gastric motility in rats. Then, the possible central and peripheral pathways that regulate gastric motility were also discussed by microinjecting SR49059 (a specific AVP receptor antagonist) into the DMV and intravenous injection of hexamethonium (a specific neuronal nicotinic cholinergic receptor antagonist) before AVP microinjection. Results. Following microinjection of AVP (180 pmol and 18 pmol) into the DMV, the gastric motility (including total amplitude, total duration, and motility index of gastric contraction) was significantly inhibited (P < 0.05). Moreover, the inhibitory effect of AVP (180 pmol) on gastric motility could be blocked completely by both SR49059 (320 pmol) and hexamethonium (8 MUmol). Conclusions. It is concluded that AVP inhibits the gastric motility by acting on the specific AVP receptor in the DMV, with the potential involvement of the parasympathetic preganglionic cholinergic fibers. PMID- 26843856 TI - A Retrospective Evaluation of the Utility of Capsule Endoscopy and Double-Balloon Endoscopy in Crohn's Disease. AB - Background. Although the usefulness of capsule endoscopy (CE) and double-balloon endoscopy (DBE) for the evaluation of Crohn's disease (CD) is established, their capabilities in the differential diagnosis of small bowel stenosis have not been sufficiently addressed. The present study therefore aimed to retrospectively determine the types of patients for whom CE and DBE would confer the most benefit. Patients and Methods. We retrospectively reviewed data from 185 patients with established CD. A change of treatment based on CE or DBE results or successful DBE balloon dilation was defined as clinically useful indication. We then analyzed the factors significantly related to useful and poor indications. Results. CE results were assessed as useful indications in 28 (45%) of 62 patients. Multivariate analysis demonstrated that positive CRP and low IOIBD score are factors significantly related to a useful indication. DBE results were recognized as useful indications in 118 (77%) of 153 patients. Multivariate analysis indicated small bowel stenosis and abdominal pain as factors significantly associated with useful indications. All patients with a poor indication on CE had small bowel stenosis. Conclusions. CE was most useful for patients in clinical remission with positive CRP and without stenosis, whereas DBE was useful for patients with symptoms of stenosis. PMID- 26843858 TI - Elevated Preoperative Neutrophil-Lymphocyte Ratio Is Associated with Poor Prognosis in Hepatocellular Carcinoma Patients Treated with Liver Transplantation: A Meta-Analysis. AB - This study aims to investigate the prognostic value of neutrophil to lymphocyte ratio (NLR) in hepatocellular carcinoma (HCC) patients treated with liver transplantation (LT) through meta-analysis. Relevant articles were sought in PubMed, Embase, and Wangfang databases up to July 2015. A total of 1687 patients from 10 studies were included in this meta-analysis. Meta-analysis results showed that elevated NLR was significantly associated with poorer overall survival (OS) (HR = 2.71, 95% CI: 1.91-3.83) and poorer disease-free survival (DFS) (HR = 3.61, 95% CI: 2.23-5.84) in HCC patients treated with LT. Moreover, subgroup analysis showed the significant association between elevated preoperative NLR and poor prognosis was not altered by cutoff values of NLR or types of LT. Therefore, elevated preoperative NLR is associated with poor prognosis in HCC patients treated with LT. Preoperative NLR should be used to predict the prognosis of HCC after LT in our clinical work. PMID- 26843859 TI - Corrigendum to "An Increased Ratio of Glycated Albumin to HbA1c Is Associated with the Degree of Liver Fibrosis in Hepatitis B Virus-Positive Patients". AB - [This corrects the article DOI: 10.1155/2014/351396.]. PMID- 26843860 TI - Thread-Traction with a Sheath of Polypectomy Snare Facilitates Endoscopic Submucosal Dissection of Early Gastric Cancers. AB - Although the thread-traction (TT) method has been found useful during endoscopic submucosal dissection (ESD) for early gastric cancers, the movement of the thread interferes with the movement of the endoscope, and the lesion can only be pulled to the mouth side. We have developed the novel TT method using a sheath of polypectomy snare (TTSPS). The TTSPS method enables free and independent movement of the thread and the endoscope and allows pulling the lesion towards the anal as well as oral side. The median dissection times, numbers of instances of arterial bleeding, and numbers of local injections into the submucosal layer were significantly lower for ESD with TTSPS than for conventional ESD. Countertraction ESD using the TTSPS method is straightforward, safe, easy, noninvasive, and cost effective, and it uses instruments readily available in most hospitals to enhance visualization of cutting lines. Therefore, the TTSPS method can be universally applied in conventional ESD. PMID- 26843861 TI - A Cross-Sectional Study of Self-Rated Health among Older Adults: Association with Drinking Profiles and Other Determinants of Health. AB - This study compares the relationship between drinking profiles and self-rated health with and without adjusting for other determinants of health among a sample of older adults from the general population. Respondents were 1,494 men and 2,176 women aged between 55 and 74 from the GENACIS Canadian survey. The dependent variable was self-rated health, an individual's perception of his or her own general health, a measure used as a proxy for health status. The independent variables were drinking profiles (types of drinkers and nondrinkers) as well as other demographic, psychosocial, and health-related variables (control variables). After adjustment for other determinants of health, regression analyses showed that (1) frequent/moderate drinkers were more likely to have a better self-rated health compared with nondrinkers (lifetime abstainers and former drinkers) and (2) self-rated health did not differ significantly between frequent/moderate drinkers and other types of drinkers (frequent/nonmoderate and infrequent drinkers). Our results suggest that drinking is related to a better self-rated health compared with nondrinking regardless of the drinking profile. Drinking and healthy lifestyle guidelines specific to older adults should be studied, discussed, and integrated into public health practices. PMID- 26843862 TI - Elevated Systemic Neutrophil Count Is Associated with Diabetic Macroalbuminuria among Elderly Chinese. AB - Background. This study investigated an association between systemic absolute neutrophil count (ANC) and albuminuria in elderly Chinese people. Methods. A cross-sectional study was conducted on 2265 participants attending a routine medical examination in Minhang District as part of a Platform of Chronic Disease program. Their drug history, waist circumference, height, blood pressure, fasting blood glucose, ANC, and urine albumin levels were recorded. This study conformed to the requirements of the STROBE statement. Results. Of the 2265 subjects, 1254 (55.4%) were diabetic and 641 (28.3%) had albuminuria. The mean ANC of patients with diabetes comorbid with macroalbuminuria was significantly higher than that of both the nondiabetic patients and patients with diabetes with lower levels of albuminuria; the latter 2 groups had statistically similar ANC. ANC significantly and positively correlated with levels of urine albumin. Based on multivariate analysis, with each 10(9)/L increase in ANC, the increase in rates of macroalbuminuria was significant but not in rates of albuminuria positivity. Based on areas under the receiver operating characteristic curve, ANC was the strongest factor predicting macroalbuminuria. Conclusions. Elevated ANC was associated with macroalbuminuria in diabetes, indicating that neutrophil-mediated inflammation may be involved in the exacerbation of albuminuria. PMID- 26843863 TI - Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors. AB - We previously showed a decreased expression of vitamin D receptor (VDR) mRNA/protein in a small group of adrenocortical carcinoma (ACC) tissues, suggesting the loss of a protective role of VDR against malignant cell growth in this cancer type. Downregulation of VDR gene expression may result from epigenetics events, that is, methylation of cytosine nucleotide of CpG islands in VDR gene promoter. We analyzed methylation of CpG sites in the VDR gene promoter in normal adrenals and adrenocortical tumor samples. Methylation of CpG-rich 5' regions was assessed by bisulfite sequencing PCR using bisulfite-treated DNA from archival microdissected paraffin-embedded adrenocortical tissues. Three normal adrenals and 23 various adrenocortical tumor samples (15 adenomas and 8 carcinomas) were studied. Methylation in the promoter region of VDR gene was found in 3/8 ACCs, while no VDR gene methylation was observed in normal adrenals and adrenocortical adenomas. VDR mRNA and protein levels were lower in ACCs than in benign tumors, and VDR immunostaining was weak or negative in ACCs, including all 3 methylated tissue samples. The association between VDR gene promoter methylation and reduced VDR gene expression is not a rare event in ACC, suggesting that VDR epigenetic inactivation may have a role in adrenocortical carcinogenesis. PMID- 26843865 TI - Carbon Sources for Yeast Growth as a Precondition of Hydrogen Peroxide Induced Hormetic Phenotype. AB - Hormesis is a phenomenon of particular interest in biology, medicine, pharmacology, and toxicology. In this study, we investigated the relationship between H2O2-induced hormetic response in S. cerevisiae and carbon sources in yeast growth medium. In general, our data indicate that (i) hydrogen peroxide induces hormesis in a concentration-dependent manner; (ii) the effect of hydrogen peroxide on yeast reproductive ability depends on the type of carbon substrate in growth medium; and (iii) metabolic and growth rates as well as catalase activity play an important role in H2O2-induced hormetic response in yeast. PMID- 26843864 TI - Protein Kinase CK2: A Targetable BCR-ABL Partner in Philadelphia Positive Leukemias. AB - BCR-ABL-mediated leukemias, either Chronic Myeloid Leukemia (CML) or Philadelphia positive Acute Lymphoblastic Leukemia (ALL), are the paradigm of targeted molecular therapy of cancer due to the impressive clinical responses obtained with BCR-ABL specific tyrosine kinase inhibitors (TKIs). However, BCR-ABL TKIs do not allow completely eradicating both CML and ALL. Furthermore, ALL therapy is associated with much worse responses to TKIs than those observed in CML. The identification of additional pathways that mediate BCR-ABL leukemogenesis is indeed mandatory to achieve synthetic lethality together with TKI. Here, we review the role of BCR-ABL/protein kinase CK2 interaction in BCR-ABL leukemias, with potentially relevant implications for therapy. PMID- 26843866 TI - Early Stage Relapsing Polychondritis Diagnosed by Nasal Septum Biopsy. AB - Relapsing polychondritis is a rare inflammation of cartilaginous tissues, the diagnosis of which is usually delayed by a mean period of 2.9 years from symptom onset. We present the case of a 36-year-old man with nasal pain and fever. Physical examination of the nose was grossly unremarkable, but there was significant tenderness of the nasal bridge. Acute sinusitis was initially diagnosed due to thickened left frontal sinus mucosa on computed tomography (CT); however, there was no improvement after antibiotic intake. Repeat CT showed edematous inflammation of the nasal septum; biopsy of this site demonstrated erosion and infiltration of lymphocytes, plasma cells, eosinophils, and neutrophils in the hyaline cartilage. Relapsing polychondritis was confirmed by the modified McAdam's criteria and can be diagnosed at an early stage by nasal septum biopsy; it should be considered as a differential diagnosis in patients presenting with nasal symptoms alone or persistent sinus symptoms. PMID- 26843867 TI - Dabigatran Associated Leukocytoclastic Vasculitis. AB - Common side effects of dabigatran are bleeding, bruising, nausea, diarrhea, and abdomen discomfort. Skin reactions were not often noted (<0.1%). We report a case of 70-year-old male who developed dabigatran related skin reaction resistant to usual therapy. Skin biopsy revealed leukocytoclastic vasculitis. PMID- 26843868 TI - High Proteolytic Resistance of Spider-Derived Inhibitor Cystine Knots. AB - Proteolytic stability in gastrointestinal tract and blood plasma is the major obstacle for oral peptide drug development. Inhibitor cystine knots (ICKs) are linear cystine knot peptides which have multifunctional properties and could become promising drug scaffolds. ProTx-I, ProTx-II, GTx1-15, and GsMTx-4 were spider-derived ICKs and incubated with pepsin, trypsin, chymotrypsin, and elastase in physiological conditions to find that all tested peptides were resistant to pepsin, and ProTx-II, GsMTx-4, and GTx1-15 showed resistance to all tested proteases. Also, no ProTx-II degradation was observed in rat blood plasma for 24 hours in vitro and ProTx-II concentration in circulation decreased to half in 40 min, indicating absolute stability in plasma and fast clearance from the system. So far, linear peptides are generally thought to be unsuitable in vivo, but all tested ICKs were not degraded by pepsin and stomach could be selected for the alternative site of drug absorption for fast onset of the drug action. Since spider ICKs are selective inhibitors of various ion channels which are related to the pathology of many diseases, engineered ICKs will make a novel class of peptide medicines which can treat variety of bothering symptoms. PMID- 26843869 TI - Management of Root Resorption Using Chemical Agents: A Review. AB - Root resorption (RR) is defined as the loss of dental hard tissues because of clastic activity inside or outside of tooth the root. In the permanent dentition, RR is a pathologic event; if untreated, it might result in the premature loss of the affected tooth. Several hypotheses have been suggested as the mechanisms of root resorption such as absence of the remnants of Hertwig's epithelial root sheath (HERS) and the absence of some intrinsic factors in cementum and predentin such as amelogenin or osteoprotegerin (OPG). It seems that a barrier is formed by the less-calcified intermediate cementum or the cementodentin junction that prevents external RR. There are several chemical strategies to manage root resorption. The purpose of this paper was to review several chemical agents to manage RR such as tetracycline, sodium hypochlorite, acids (citric acid, phosphoric acid, ascorbic acid and hydrochloric acid), acetazolamide, calcitonin, alendronate, fluoride, Ledermix and Emdogain. PMID- 26843870 TI - Antibacterial Activity of Diode Laser and Sodium Hypochlorite in Enterococcus Faecalis-Contaminated Root Canals. AB - INTRODUCTION: The aim of the present in vitro study was to evaluate the disinfection ability of 980-nm diode laser in comparison with sodium hypochlorite (NaOCl) as a common root canal irrigant in canals infected with Enterococcus faecalis (E. faecalis). METHODS AND MATERIALS: The root canals of 18 extracted single-rooted premolars were prepared by rotary system. After decoronation, the roots were autoclaved. One specimen was chosen for the negative control, and the remaining teeth were incubated with E. faecalis suspension for two weeks. Subsequently, one specimen was selected as the positive control and the remaining samples were divided into two groups (n=8). The samples of the first group were irrigated with 5.25% NaOCl and the second group were treated with a 980-nm diode laser. Microbial samples were taken from the root canals and bacterial cultivation was carried out. The average value and the standard deviation of colony-forming units (CFU) of each specimen were measured using descriptive statistics. The student's t-test was used to compare the reduction in CFU in each group. The equality of variance of CFU was measured by the Levene's test. RESULTS: NaOCl resulted in 99.87% removal of the bacteria and showed significantly more antibacterial effect compared to the 980-nm diode laser which led to 96.56% bacterial reduction (P<0.05). CONCLUSION: Although 5.25% NaOCl seems to reduce E. faecalis more effectively, the diode laser also reduced the bacterial count. Therefore a 980-nm diode laser could be considered as a complementary disinfection method in root canal treatment. PMID- 26843871 TI - Tissue Reaction and Biocompatibility of Implanted Mineral Trioxide Aggregate with Silver Nanoparticles in a Rat Model. AB - INTRODUCTION: Biocompatibility and antimicrobial activity of endodontic materials are of utmost importance. Considering the extensive applications of mineral trioxide aggregate (MTA) in dentistry and antimicrobial properties of silver nanoparticles, this study aimed to evaluate the subcutaneous inflammatory reaction of rat connective tissues to white MTA with and without nanosilver (NS) particles. METHODS AND MATERIALS: Polyethylene tubes (1.1*8 mm) containing experimental materials (MTA and MTA+NS and empty control tubes) were implanted in subcutaneous tissues of seventy-five male rats. Animals were divided into five groups (n=15) according to the time of evaluation: group 1; after 7 days, group 2; after 15 days, group 3; after 30 days, group 4; after 60 days and group 5; after 90 days. The inflammatory reaction was graded and data was analyzed using the Kruskal-Wallis and Mann-Whitney U tests. Statistical significance was defined at 0.05. RESULTS: Comparison of cumulative inflammatory reaction at all intervals revealed that the mean grade of inflammatory reaction to MTA, MTA+NS and control samples were 3, 2 and 2, respectively. According to the Mann-Whitney analysis there were no significant differences between MTA+NS and MTA (P=0.42). CONCLUSION: Incorporation of 1% nanosilver to MTA does not affect the inflammatory reaction of subcutaneous tissue in rat models. PMID- 26843872 TI - Cytotoxicity of Various Endodontic Materials on Stem Cells of Human Apical Papilla. AB - INTRODUCTION: This in vitro study assessed and compared the cytotoxicity of mineral trioxide aggregate (MTA), calcium-enriched mixture (CEM) cement, Biodentine (BD) and octacalcium phosphate (OCP) on stem cells of the human apical papilla (SCAP). METHODS AND MATERIALS: SCAPs were isolated from two semi-impacted third molars. The cells were cultured in wells of an insert 24-well plate and were then incubated. The plates were then removed from the incubator and randomly divided into four experimental groups that were exposed to 1-mm discs of set MTA, CEM, BD or OCP, and one untreated control group. After 24, 48 and 168 h, the plates were removed from the incubator and 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyl tetrazolium bromide (MTT) solution was added to each well. Data were analyzed at different time points using the repeated measures ANOVA followed by Bonferroni test and the level of significance was set at 0.05. RESULTS: Cytotoxicity of the four materials was not significantly different from that of the control group at 24, 48 and 168 h (P>0.05). Two-by-two comparison revealed that cytotoxicity of MTA and CEM cement was significantly different from each other at 168 h (P<0.05) although the cytotoxicity of CEM was less than MTA. Cytotoxicity of OCP and MTA was also significantly different from each other at 48 h and OCP had more favorable biocompatibility than MTA (P<0.05). CONCLUSION: CEM, OCP, BD and MTA showed acceptable biocompatibility when exposed to SCAP. Over time, CEM showed the least cytotoxicity among the materials under study. PMID- 26843873 TI - Coronal Discoloration Induced by Calcium-Enriched Mixture, Mineral Trioxide Aggregate and Calcium Hydroxide: A Spectrophotometric Analysis. AB - INTRODUCTION: The aim of this study was to compare the discoloration potential of calcium-enriched mixture (CEM) cement, white mineral trioxide aggregate (WMTA) and calcium hydroxide (CH), after placement in pulp chamber. METHODS AND MATERIALS: Access cavities were prepared in 40 intact maxillary central incisors. Then, a 2*2 mm box was prepared on the middle third of the inner surface on the buccal wall of the access cavity. The specimens were randomly assigned into four groups; the boxes in the control group were left empty, in groups 1 to 3, the boxes were filled with CH, WMTA and CEM cement, respectively. The access cavities and the apical openings were sealed using resin modified glass ionomer (RMGI). The color measurement was performed with a spectrophotometer at the following intervals: before (T0), immediately after placement of the filling material (T1), one week (T2), 1 month (T3), 3 months (T4) and 5 months (T5) after filling of the box and finally immediately after removing the material from the boxes (T6). Color change (Delta E) values were calculated using the sample Kolmogorov-Smirnov test to determine the normal distribution of data, followed by ANOVA, repeated measured ANOVA and post-hoc Tukey's tests. RESULTS: All materials led to clinically perceptible crown discoloration after 1 week. The highest DeltaE value belonged to WMTA group. Discoloration induced by CEM cement was not significantly different from CH or the control group (P>0.05). CONCLUSION: CEM cement may be the material of choice in the esthetic region, specifically pertaining to its lower color changing potential compared to WMTA. PMID- 26843874 TI - Effect of Autoclave Cycles on Surface Characteristics of S-File Evaluated by Scanning Electron Microscopy. AB - INTRODUCTION: Presence of surface defects in endodontic instruments can lead to unwanted complications such as instrument fracture and incomplete preparation of the canal. The current study was conducted to evaluate the effect of autoclave cycles on surface characteristics of S-File by scanning electron microscopy (SEM). METHODS AND MATERIALS: In this experimental study, 17 brand new S-Files (#30) were used. The surface characteristics of the files were examined in four steps (without autoclave, 1 autoclave cycle, 5 autoclave cycles and 10 autoclave cycles) by SEM under 200* and 1000* magnifications. Data were analyzed using the SPSS software and the paired sample t-test, independent sample t-test and multifactorial repeated measures ANOVA. The level of significance was set at 0.05. RESULTS: New files had debris and pitting on their surfaces. When the autoclave cycles were increased, the mean of surface roughness also increased at both magnifications (P<0.05). Moreover, under 1000* magnification the multifactorial repeated measures ANOVA showed more surface roughness (P<0.001). CONCLUSION: Sterilization by autoclave increased the surface roughness of the files and this had was directly related to the number of autoclave cycles. PMID- 26843875 TI - Effects of Glide Path on the Centering Ability and Preparation Time of Two Reciprocating Instruments. AB - INTRODUCTION: The aim of this in vitro study was to evaluate the effects of establishing glide path on the centering ability and preparation time of two single-file reciprocating systems in mesial root canals of mandibular molars. METHODS AND MATERIALS: Sixty extracted mandibular molars with curvatures of 25-39 degrees and separate foramina for the mesiobuccal and mesiolingual canals, were divided into four groups (n=15); WaveOne+glide path; WaveOne; Reciproc+glide path and Reciproc. Non-patent canals were excluded and only one canal in each tooth was instrumented. A manual glide path was established in first and third groups with #10, 15 and 20 hand K-files. Preparation was performed with reciprocating in and-out motion, with a 3-4 mm amplitude and slight apical pressure. Initial and final radiographs were taken to analyze the amount of dentin removed in the instrumented canals. The radiographs were superimposed with an image editing software and examined to assess discrepancies at 3-, 6- and 9-mm distances from the apex. The Kruskal-Wallis test was used for statistical analysis. The level of significance was set at 0.05. RESULTS: Preparation in groups without glide paths was swifter than the other groups (P=0.001). However, no difference was observed regarding centering ability. CONCLUSION: Establishing a glide path increased the total instrumentation time for preparing curved canals with WaveOne and Reciproc instruments. Glide path had no influence on the centering ability of these systems. PMID- 26843876 TI - Postoperative Pain after Endodontic Treatment of Asymptomatic Teeth Using Rotary Instruments: A Randomized Clinical Trial. AB - INTRODUCTION: The aim of the present study was to compare the effect of two different rotary instruments on postoperative pain in teeth with asymptomatic irreversible pulpitis. METHODS AND MATERIALS: A total of 78 mandibular first and second molars were divided into two groups (n=39) and their root canal preparation was carried out with either RaCe or ProTaper rotary instruments. All the subjects underwent one-visit root canal treatment and the severity of postoperative pain was evaluated using visual analog scale (VAS) at 4-, 12-, 24-, 48- and 72-h and 1-week intervals. In addition, the need for taking analgesics was recorded. Data were analyzed with the repeated-measures ANOVA and the Mann Whitney U test was used for two-by-two comparison. Statistical significance was set at 0.05. RESULTS: Comparison of mean pain severity between the two groups at various postoperative intervals did not reveal any significant differences (P=0.10). The difference in amount of analgesics taken by each groups was not statistically significant (P=0.25). CONCLUSION: There were no significant differences in the postoperative pain reported between the two groups; which indicates the clinical acceptability of both systems. PMID- 26843877 TI - Antimicrobial and Cytotoxic Activity of Cuminum Cyminum as an Intracanal Medicament Compared to Chlorhexidine Gel. AB - INTRODUCTION: The aims of this study were i) to define the chemical constituents of Cuminum cyminum (cumin) essential oil, ii) to compare the antimicrobial activity of this oil to that of chlorhexidine (CHX) and co-trimoxazole on planktonic and biofilm forms of bacteria isolated from the teeth with persistent endodontic infection and iii ) to compare the cytotoxicity of these medicaments on L929 fibroblasts. METHODS AND MATERIALS: Three groups of microorganisms [aerobic bacterial mixture, anaerobic bacterial mixture and Enterococcus faecalis (E .faecalis)] were isolated from the teeth with persistent apical periodontitis. Zone of inhibition (ZOI), minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC) and time-kill tests were performed to assess the antimicrobial efficacy of the medicaments. Further, a cytocompatibility analysis of the medicaments was performed on L929 fibroblasts. The results obtained from disc diffusion test and mean cell viability values of the experimental medicaments were analyzed using two-way and one-way analysis of variance (ANOVA). RESULTS: Seventeen constituents were recognized in cumin oil (predominantly cumin aldehyde and gamma-terpinene). Co-trimoxazole showed the greatest ZOI followed by cumin and CHX. The smallest MIC and MBC belonged to co-trimoxazole followed by cumin and CHX for all groups of bacteria except for E. faecalis for which the MBC of cumin was smaller than co trimoxazole. The results of time-kill assay revealed that all medicaments totally inhibited the bacterial growth in all groups after 24 h. CHX was the most cytotoxic solution while there were no significant differences between the cytocompatibility of different concentrations of cumin essential oil and co trimoxazole. CONCLUSION: Cumin exhibited a strong antimicrobial efficiency against the microbial flora of the teeth with failed endodontic treatments and it was biocompatible for L929 mouse fibroblasts. PMID- 26843878 TI - Diagnostic Accuracy of Cone-Beam Computed Tomography and Periapical Radiography in Internal Root Resorption. AB - INTRODUCTION: The aim of this study was to compare the diagnostic value of cone beam computed tomography (CBCT) and periapical (PA) radiography in detecting internal root resorption. METHODS AND MATERIALS: Eighty single rooted human teeth with visible pulps in PA radiography were split mesiodistally along the coronal plane. Internal resorption like lesions were created in three areas (cervical, middle and apical) in labial wall of the canals in different diameters. PA radiography and CBCT images were taken from each tooth. Two observers examined the radiographs and CBCT images to evaluate the presence of resorption cavities. The data were statistically analyzed and degree of agreement was calculated using Cohen's kappa (k) values. RESULTS: The mean+/-SD of agreement coefficient of kappa between the two observers of the CBCT images was calculated to be 0.681+/ 0.047. The coefficients for the direct, mesial and distal PA radiography were 0.405+/-0.059, 0.421+/-0.060 and 0.432+/-0.056, respectively (P=0.001). The differences in the diagnostic accuracy of resorption of different sizes were statistically significant (P<0.05); however, the PA radiography and CBCT, had no statistically significant differences in detection of internal resorption lesions in the cervical, middle and apical regions. CONCLUSION: Though, CBCT has a higher sensitivity, specificity, positive predictive value and negative predictive value in comparison with conventional radiography, this difference was not significant. PMID- 26843881 TI - Bisphosphonate-Induced Osteonecrosis of the Maxilla Resembling a Persistent Endodontic Lesion. AB - A 52-year-old Caucasian woman suffering from pain in the anterior maxillary region, presented to the clinic. Examination revealed a draining sinus tract in the buccal vestibule of the maxilla in the left anterior segment and expansion in the middle of palate. On conventional radiographic examination the lesion was initially assumed to be a periapical problem related to the incisors but subsequently it was diagnosed to be a bisphosphonate osteonecrosis. CONCLUSION: Acquiring a comprehensive medical history from the patients, conducting the clinical vitality tests and most importantly being familiar with the non odontogenic lesions that can be side effects of specific medications are important requirements for reaching a correct diagnosis. PMID- 26843879 TI - Effect of Premedication with Indomethacin and Ibuprofen on Postoperative Endodontic Pain: A Clinical Trial. AB - INTRODUCTION: Post-endodontic pain is one of the main problems for both patients and dentists. The purpose of this study was to compare the effectiveness of premedication with indomethacin and ibuprofen for management of postoperative endodontic pain. METHODS AND MATERIALS: In this clinical trial, mandibular molars with irreversible pulpitis were endodontically treated in 66 patients. The medicines were prepared similarly in the form of capsules containing 400 mg ibuprofen (group A), 25 mg indomethacin (group B) and placebo (group C). The patients were given one capsule 1 h before the start of treatment. Patients recorded their pain measured by a visual analogue scale (VAS) at medication time, during treatment and 8, 12 and 24 h after treatment. The data were analyzed using the chi-square, repeated measures ANOVA, paired t-test, Tamhane and Pearson correlation coefficient. RESULTS: Ibuprofen and indomethacin significantly reduced the postoperative pain in comparison with placebo during treatment and 8 h after treatment; however, there were no significant differences between them 12 and 24 h after treatment. CONCLUSION: Premedication with ibuprofen and indomethacin can effectively control short term post-operative pain; the lower incidence of side effects and greater analgesic power of ibuprofen make it a superior choice. PMID- 26843880 TI - The Impact of Apical Patency in the Success of Endodontic Treatment of Necrotic Teeth with Apical Periodontitis: A Brief Review. AB - Accumulation of soft tissue or dentinal remnants in the apical region is a common event that can cause blockage of root canals. This event can be avoided if apical patency is performed during the root canal shaping procedures. However, there is no consensus on the role of apical patency in relation to the success of endodontic treatment of necrotic teeth with apical periodontitis. Therefore, the purpose of this paper was to conduct a brief review on the role of apical patency in guaranteeing the success of endodontic treatments of necrotic teeth with apical periodontitis considering two other key points; the root canal anatomy and microbiology. PMID- 26843882 TI - Interdisciplinary Approach for Management of Iatrogenic Internal Root Resorption: A Case Report. AB - For management of a symptomatic maxillary lateral incisor with dull pain on chewing, suppurative sinus tract, defective metal-ceramic crown and iatrogenic internal root resorption, an interdisciplinary approach was taken. Two-visit nonsurgical treatment with calcium-enriched mixture (CEM) cement, replacement of metal-ceramic crown with all-ceramic crown and corrective periodontal plastic surgery were included in the treatment plan. Six-month and one-year follow-ups revealed complete resolution of signs and symptoms and radiographic healing. This case report highlights the importance of adequate cooling during crown preparation to preserve the pulp vitality and prevent internal resorptive lesions and also the profound sealing ability and biocompatibility of CEM cement. PMID- 26843884 TI - Computational models of heart disease. PMID- 26843883 TI - Miniature Pulpotomy of Symptomatic Mature Permanent Teeth: A Report of Two Cases. AB - Human dental pulp inflammation can progress to periapical lesion formation and conventional root canal treatment (RCT) has been the traditional method for disease management. This observational study presents two cases of vital pulp therapy in mature molars diagnosed with irreversible pulpitis and associated with apical periodontitis. In these two clinical cases, the involved teeth had deep carious lesions with a history of spontaneous/lingering pain and radiographic examinations revealed the presence of apical radiolucencies. A conservative miniature pulpotomy (MP) using calcium-enriched mixture (CEM) was performed and the teeth were permanently restored with amalgam. Clinical evaluations indicated resolution of pain 24 hours after treatment; the teeth showed normal vitality, remained asymptomatic and maintained normal function after recall examinations. Furthermore, the 18-month radiographic evaluation showed healing of the apical lesions. Vital pulp therapy using the MP technique with CEM appeared successful in avoiding RCT intervention. These two reports of case outcome suggest that simple MP using a CEM bioregenerative technique may provide a favorable outcome for permanent teeth diagnosed with irreversible pulpitis and associated with apical periodontitis. PMID- 26843885 TI - Oleanolic Acid Attenuates Insulin Resistance via NF-kappaB to Regulate the IRS1 GLUT4 Pathway in HepG2 Cells. AB - The aim of our study is to elucidate the mechanisms of oleanolic acid (OA) on insulin resistance (IR) in HepG2 cells. HepG2 cells were induced with FFA as the insulin resistance model and were treated with OA. Then the glucose content and the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were analyzed. Moreover, protein expression of nuclear factor kappa B (NF kappaB), insulin receptor substrate 1(IRS1), and glucose transporter 4 (GLUT4) in cells treated with OA were measured by Western blot analysis. Additionally, IRS1 protein expression exposed to OA was detected after using pyrrolidine dithiocarbamate (PDTC).Our results revealed that OA decreased the glucose content in HepG2 cells in vitro. Moreover, OA reduced the levels of TNF-alpha and IL-6 and upregulated IRS1 and GLUT4 protein expression. Furthermore, OA also reduced NF-kappaB protein expression in insulin-resistant HepG2 cells. After blocking NF kappaB, the expression of IRS1 protein had no obvious changes when treated with OA. OA attenuated insulin resistance and decreased the levels of TNF-alpha and IL 6. Meanwhile, OA decreased NF-kappaB protein expression and upregulated IRS1 and GLUT4 protein expression. Therefore, regulating the IRS1-GLUT4 pathway via NF kappaB was the underlying mechanism of OA on insulin resistance. PMID- 26843887 TI - Scientific Evidence for Korean Medicine and Its Integrative Medical Research. PMID- 26843886 TI - Acupuncture for Lateral Epicondylitis: A Systematic Review. AB - Objective. This systematic review aimed to assess the effectiveness and safety of acupuncture for lateral epicondylitis (LE). Methods. Seven databases and the WHO International Clinical Trials Registry Platform Search Portal were searched to identify relevant studies. The data were extracted and assessed by two independent authors, and Review Manager Software (V.5.3) was used for data synthesis with effect estimate presented as standard mean difference (SMD) and mean difference (MD) with a 95% confidence interval. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the level of evidence. Results. Four RCTs with 309 participants were included with poor methodological quality. Participants who received acupuncture and acupuncture plus moxibustion with material insulation were likely to have an improvement in elbow functional status and/or myodynamia. The overall quality rated by GRADE was from very low to low. Two studies reported that the needle pain would be the main reason for the dropout. Conclusion. For the small number of included studies with poor methodological quality, no firm conclusion can be drawn regarding the effect of acupuncture of elbow functional status and myodynamia for LE. This trial is registered with CRD42015016199. PMID- 26843888 TI - Spatial compartmentalization of free radical formation and mitochondrial heterogeneity in bivalve gills revealed by live-imaging techniques. AB - BACKGROUND: Reactive oxygen (ROS) and nitrogen (RNS) species are produced during normal unstressed metabolic activity in aerobic tissues. Most analytical work uses tissue homogenates, and lacks spatial information on the tissue specific sites of actual ROS formation. Live-imaging techniques (LIT) utilize target specific fluorescent dyes to visualize biochemical processes at cellular level. RESULTS: Together with oxidative stress measurements, here we report application of LIT to bivalve gills for ex-vivo analysis of gill physiology and mapping of ROS and RNS formation in the living tissue. Our results indicate that a) mitochondria located in the basal parts of the epithelial cells close to the blood vessels are hyperpolarized with high Deltapsim, whereas b) the peripheral mitochondria close to the cilia have low (depolarized) Deltapsim. These mitochondria are densely packed (mitotracker Deep Red 633 staining), have acidic pH (Ageladine-A) and collocate with high formation of nitric oxide (DAF-2DA staining). NO formation is also observed in the endothelial cells surrounding the filament blood sinus. ROS (namely H2O2, HOO(*) and ONOO(-) radicals, assessed through C-H2DFFDA staining) are mainly formed within the blood sinus of the filaments and are likely to be produced by hemocytes as defense against invading pathogens. On the ventral bend of the gills, subepithelial mucus glands contain large mucous vacuoles showing higher fluorescence intensities for O2 (*-) than the rest of the tissue. Whether this O2 (*-) production is instrumental to mucus formation or serves antimicrobial protection of the gill surface is unknown. Cells of the ventral bends contain the superoxide forming mucocytes and show significantly higher protein carbonyl formation than the rest of the gill tissue. CONCLUSIONS: In summary, ROS and RNS formation is highly compartmentalized in bivalve gills under unstressed conditions. The main mechanisms are the differentiation of mitochondria membrane potential and basal ROS formation in inner and outer filament layers, as well as potentially antimicrobial ROS formation in the central blood vessel. Our results provide new insight into this subject and highlight the fact that studying ROS formation in tissue homogenates may not be adequate to understand the underlying mechanism in complex tissues. PMID- 26843890 TI - Neuro-ophthalmology of type 1 Chiari malformation. AB - Chiari malformation is a congenital deformity leading to herniation of cerebellar tonsils. Headache is a typical symptom of this condition, but patients with Chiari malformation often present with double vision and vertigo. Examination of eye movements in such patients often reveals nystagmus and strabismus. Eye movement deficits in the context of typical symptomatic presentation are critical clinical markers for the diagnosis of Chiari malformation. We will review eye movement deficits that seen in patients with type 1 Chiari malformation. We will then discuss the underlying pathophysiology and therapeutic options for such deficits. PMID- 26843889 TI - EBV glycoproteins: where are we now? AB - Glycoproteins are critical to virus entry, to spread within and between hosts and can modify the behavior of cells. Many viruses carry only a few, most found in the virion envelope. EBV makes more than 12, providing flexibility in how it colonizes its human host. Some are dedicated to getting the virus through the cell membrane and on toward the nucleus of the cell, some help guide the virus back out and on to the next cell in the same or a new host. Yet others undermine host defenses helping the virus persist for a lifetime, maintaining a presence that is mostly tolerated and serves to perpetuate EBV as one of the most common infections of man. PMID- 26843892 TI - Enzyme disintegration with spatial resolution reveals different distributions of sludge extracellular polymer substances. AB - BACKGROUND: To understand the intrinsic role of hydrolytic enzymes in sludge treatment, particularly their effect on the digestibility and dewaterability of sludge, activated sludge flocs were disintegrated using various techniques that included different enzymes (amylase, cellulase, proteinase, DNase, and polygalacturonase), pH adjustment, and temperature adjustment. The effectiveness of each enzyme treatment was pinpointed by quantifying the spatial distribution of each type of organic matters (protein, polysaccharide, DNA, fluorescent organics) in outer layer extracellular polymeric substances (EPS), inner layer EPS, and cells. RESULTS: Most hydrolytic enzymes functioned only owing to a temperature or pH effect. The release of organic matter from the interior fraction of EPS to the exterior fraction was prompted under high pH and temperature even without enzyme addition. The effectiveness of enzyme addition was only significant for cellulase and polygalacturonase treatments. Polygalacturonase unexpectedly increased the total EPS polysaccharides up to seven times, accompanied with improved dewaterability, while the amount of EPS proteins was almost unchanged. Combining chemical and morphological evidence, a new conceptual model considering the spatial distribution of polygalacturonic acid-like matter, proteins, cellulose, and other organics in EPS was proposed. CONCLUSIONS: Polygalacturonic acid-like matter hydrolysis caused significant release of polysaccharides. Polygalacturonase released polysaccharides while keeping proteins unreleased. Temperature and pH adjustment were as effective as enzyme at sludge disintegration. Cellulose hydrolysis led to massive release of all kinds of organic matters. A new conceptual sludge structure model regarding organic components is proposed. PMID- 26843891 TI - Molecular identification of Uncaria (Gouteng) through DNA barcoding. AB - BACKGROUND: While DNA barcoding is an important technology for the authentication of the botanical origins of Chinese medicines, the suitable markers for DNA barcoding of the genus Uncaria have not been reported yet. This study aims to determine suitable markers for DNA barcoding of the genus Uncaria (Gouteng). METHODS: Genomic DNA was extracted from the freshly dried leaves of Uncaria plants by a Bioteke's Plant Genomic DNA Extraction Kit. Five candidate DNA barcode sites (ITS2, rbcL, psbA-trnH, ITS, and matK) were amplified by PCR with established primers. The purified PCR products were bidirectionally sequenced with appropriate amplification primers in an ABI-PRISM3730 instrument. The candidate DNA barcodes of 257 accessions of Uncaria in GenBank were aligned by ClustalW. Sequence assembly and consensus sequence generation were performed with CodonCode Aligner 3.7.1. The identification efficiency of the candidate DNA barcodes was evaluated with BLAST and nearest distance methods. The interspecific divergence and intraspecific variation were assessed by the Kimura 2-Parameter model. Genetic distances were computed with Molecular Evolutionary Genetics Analysis 6.0. RESULTS: The accessions of the five candidate DNA barcodes from 11 of 12 species of Uncaria in China and four species from other countries were included in the analysis, while 54 of total accessions were submitted to GenBank. In a comparison of the interspecific genetic distances of the five candidate barcodes, psbA-trnH exhibited the highest interspecific divergence based on interspecific distance, theta prime, and minimum interspecific distance, followed by ITS2. The distribution of the interspecific distance of ITS2 and psbA-trnH was higher than the corresponding intraspecific distance. Additionally, psbA-trnH showed 95.9 % identification efficiency by both the BLAST and nearest distance methods regardless of species or genus level. ITS2 exhibited 92.2 % identification efficiency by the nearest distance method, but 87 % by the BLAST method. CONCLUSION: While psbA-trnH and ITS2 (used alone) were applicable barcodes for species authentication of Uncaria, psbA-trnH was a more suitable barcode for authentication of Uncaria macrophylla. PMID- 26843893 TI - Erratum to: BioDB extractor: customized data extraction system for commonly used bioinformatics databases. AB - [This corrects the article DOI: 10.1186/s13040-015-0067-z.]. PMID- 26843894 TI - Delivering telemedicine interventions in chronic respiratory disease. PMID- 26843895 TI - Post-reconstitution Stability of Telavancin with Commonly Used Diluents and Intravenous Infusion Solutions. AB - OBJECTIVE: The post-reconstitution chemical stability and microbial challenge hold time of nonpreserved telavancin for injection was determined using common reconstitution diluents and intravenous (IV) infusion solutions stored at room temperature with light (ambient) or at 2 degrees C to 8 degrees C without light (refrigeration). METHODS: Telavancin was reconstituted with 5% dextrose, 0.9% normal saline, or sterile water (15 mg/mL). Infusion solutions at 0.6 and 8.0 mg/mL were prepared in ViaFlex (polyvinyl chloride) IV bags (Baxter International Inc, Deerfield, Illinois) using 5% dextrose, 0.9% normal saline, or lactated Ringer's solution. Chemical stability was evaluated for up to 14 days under refrigeration and for up to 3 days under ambient conditions. Telavancin concentration and degradant levels were determined using a stability-indicating HPLC method. Solutions were subjected to microbial-challenge testing for up to 48 hours (ambient) or for up to 6 days (refrigeration). RESULTS: All reconstituted or infused telavancin solutions met the prespecified stability acceptance criteria after 2 days under ambient and minimum 7 days under refrigeration. Following inoculation with gram-positive and gram-negative microorganisms, telavancin infusion solutions stored under ambient conditions reduced or inhibited populations of all organisms up to 48 hours, except for Serratia marcescens, which exhibited growth of >0.5 log10 after 12 hours. All refrigerated samples inhibited or reduced bacterial populations up to 6 days. CONCLUSIONS: These results are supportive of a total hold time for reconstituted telavancin in vials plus the time in IV infusion solutions in polyvinyl chloride bags to not exceed 12 hours under ambient conditions and 7 days under refrigeration. PMID- 26843896 TI - Investigating the Glucagon Receptor and Glucagon-Like Peptide 1 Receptor Activity of Oxyntomodulin-Like Analogues in Male Wistar Rats. AB - AIMS: To investigate the effect of Glu-3 OXM-like analogues on food intake and bodyweight in male rats. BACKGROUND: Oxyntomodulin (OXM) is a natural agonist at both the glucagon receptor (GCGr) and the glucagon-like peptide 1 receptor (GLP 1r), and peripheral administration reduces food intake and increases energy expenditure in rodents and humans. Substituting the native glutamine (Gln) at amino acid position 3 of OXM for glutamate (Glu) has previously been shown to diminish GCGr activity without affecting GLP-1r activity. The effects of Glu-3 OXM analogues have not been investigated in rats. METHODS: The effect of 2 Glu-3 substituted OXM-like analogues (eg, OXM14E3 and OXM15E3) on food intake and body weight was investigated in male Wistar rats during 6 days of daily subcutaneous (SC) administration. The effects of Glu-3 substitution on analogue binding and activity at the rat GCGr and rat GLP-1 receptor were investigated in vitro using Chinese hamster ovary or Chinese hamster lung cells. RESULTS: We report the novel finding that 2 5-nmol/kg Glu-3 OXM-like analogues (OXM14E3 and OXM15E3) significantly increased rat body weight by up to 4% compared with the equivalent non-Glu-3 analogues (OXM14 and OXM15), without affecting food intake. The effect of OXM15E3 on body weight was dose-dependent. Glu-3 analogues, including Glu-3 OXM, decreased glucagon-mediated cyclic adenosine monophosphate accumulation in Chinese hamster ovary cells expressing the rat GCGr, suggesting they may be acting as antagonists. CONCLUSIONS: The results indicate Glu-3 OXM-like analogues might not be suitable tools to investigate the mechanism of OXM analogue action in a rat model because they significantly increase body weight independent of food intake. Glu-3 OXM analogues are partial agonists at the rat GCGr and may also act as antagonists, possibly resulting in the observed increase in body weight. PMID- 26843897 TI - Bioequivalence of Alendronate and Vitamin D3 in a Combination Tablet Versus Corresponding-Dose Individual Tablets in Healthy Taiwanese Volunteers, Determined Using a Novel Plasma Alendronate Assay. AB - OBJECTIVE: This study was designed to demonstrate that alendronate (ALN)/vitamin D3 combination tablets (ALN/D5600) are bioequivalent to corresponding doses of ALN and vitamin D3 as individual tablets in healthy Taiwanese volunteers. METHODS: In this open-label, randomized, 2-period, crossover study, 68 volunteers were randomized to a single ALN/D5600 combination tablet or corresponding doses of 70 mg ALN + 5600 IU vitamin D3 (2 * 2800 IU), followed by a 12-day washout period and administration of the alternate formulation. Plasma ALN levels were measured using a newly developed assay. Geometric mean ratios of ALN AUC0-last, AUC0-infinity, and Cmax, and unadjusted vitamin D3 AUC0-80h and Cmax were compared and considered bioequivalent if the 90% CI was within 0.8 to 1.25. RESULTS: The geometric mean ratios were: AUC0-last, 1.084 (90% CI, 0.937-1.253); AUC0-infinity, 1.081 (90% CI, 0.935-1.249); and Cmax, 1.112 (90% CI, 0.959-1.289) for ALN, and AUC0-80h 0.953 (90% CI, 0.827-1.098) and Cmax, 0.982 (90% CI, 0.854 1.130) for vitamin D3 unadjusted for endogenous levels. CONCLUSIONS: The combination tablet was considered bioequivalent to coadministration based on ALN AUC0-infinity and unadjusted vitamin D3 parameters. Slight differences for ALN AUC0-last and Cmax (upper 90% CIs outside the bounds) were not considered clinically significant. The combination tablet was well tolerated. No serious adverse experiences were reported. (c) 2015. The Authors. Published by Elsevier Inc. All rights reserved. PMID- 26843899 TI - Educating the Psychology Workforce in the Age of the Affordable Care Act: A Graduate Course Modeled after the Priorities of the Patient-Centered Outcomes Research Institute (PCORI). AB - The Affordable Care Act (ACA) represents a paradigm shift in the U.S. healthcare system, which has implications for psychology programs producing the next generation of trainees. In particular, the ACA has established the Patient Centered Outcomes Research Institute (PCORI), which has been tasked with developing national priorities and funding research aimed at improving healthcare quality by helping patients and providers to make informed healthcare decisions. PCORI's national priorities span five broad domains: person-centered outcomes research, health disparities research, healthcare systems research, communication and dissemination research, and methodologic research. As these national priorities overlap with the knowledge and skills often emphasized in psychology training programs, initiatives by training programs to bolster strengths in these domains could place trainees at the forefront of this emerging research paradigm. As a part of a new Masters program in behavioral health, our program developed a health psychology course modeled around PCORI's five national priorities, and an initial evaluation in a small sample supported student learning in the five PCORI domains. In summary, the current report has implications for familiarizing readers with PCORI's national priorities for U.S. healthcare, stimulating debate surrounding psychology's response to the largest healthcare paradigm shift in recent U.S. history, and providing a working model for programs seeking to implement PCORI-related changes to their curricula. PMID- 26843898 TI - Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland. AB - BACKGROUND: Mutations in the BRCA1, BRCA2 and PALB2 genes are well-established risk factors for the development of breast and/or ovarian cancer. The frequency and spectrum of mutations in these genes has not yet been examined in the population of Southern Poland. METHODS: We examined the entire coding sequences of the BRCA1 and BRCA2 genes and genotyped a recurrent mutation of the PALB2 gene (c.509_510delGA) in 121 women with familial and/or early-onset breast or ovarian cancer from Southern Poland. RESULTS: A BRCA1 mutation was identified in 11 of 121 patients (9.1 %) and a BRCA2 mutation was identified in 10 of 121 patients (8.3 %). Two founder mutations of BRCA1 accounted for 91 % of all BRCA1 mutation carriers (c.5266dupC was identified in six patients and c.181 T > G was identified in four patients). Three of the seven different BRCA2 mutations were detected in two patients each (c.9371A > T, c.9403delC and c.1310_1313delAAGA). Three mutations have not been previously reported in the Polish population (BRCA1 c.3531delT, BRCA2 c.1310_1313delAAGA and BRCA2 c.9027delT). The recurrent PALB2 mutation c.509_510delGA was identified in two patients (1.7 %). CONCLUSIONS: The standard panel of BRCA1 founder mutations is sufficiently sensitive for the identification of BRCA1 mutation carriers in Southern Poland. The BRCA2 mutations c.9371A > T and c.9403delC as well as the PALB2 mutation c.509_510delGA should be included in the testing panel for this population. PMID- 26843900 TI - Impact of Psychiatric Information on Potential Jurors in Evaluating High Functioning Autism Spectrum Disorder (hfASD). AB - During a trial involving an offender with a mental disorder, jurors are often required to evaluate information on the disorder and its characteristics. This evaluation relies on how jurors understand and synthesize psychiatric and other evidence on the disorder and this information's impact on the case, an offender's culpability, and the rendered verdict. The importance of this evaluation is further highlighted when jurors are faced with evaluating a disorder that may be associated with criminal actions of diagnosed offenders, such as high-functioning autism spectrum disorder (hfASD). We designed a three-part survey to assess potential jurors' attitudes concerning an offender's diagnosis with hfASD in terms of perceptions and decisions surrounding legal and moral responsibility, personal characteristics of the offender, the introduction of psychiatric and genetic information, and the condition's influence on the facts of the case. A sample of 623 jury-eligible U.S. adults completed the survey. We found the majority of participants were influenced by the information provided on hfASD. Most respondents indicated that hfASD diagnosis should generally not affect the legal responsibility of an offender, but many reported the disorder as a mitigating factor when evaluating moral responsibility and legal consequences for criminal actions. Respondents reported favorable and sympathetic perceptions of individuals with autism and associated characteristics but were unsure, even after the presentation of psychiatric information on hfASD, if these disorders should be classified as "mental illness." Further, the majority reported their views were in some way influenced by the fact that hfASD has potential genetic origins. PMID- 26843901 TI - Foliar endophytic fungi as potential protectors from pathogens in myrmecophytic Acacia plants. AB - In defensive ant-plant interactions myrmecophytic plants express reduced chemical defense in their leaves to protect themselves from pathogens, and it seems that mutualistic partners are required to make up for this lack of defensive function. Previously, we reported that mutualistic ants confer plants of Acacia hindsii protection from pathogens, and that the protection is given by the ant-associated bacteria. Here, we examined whether foliar endophytic fungi may potentially act as a new partner, in addition to mutualistic ants and their bacteria inhabitants, involved in the protection from pathogens in myrmecophytic Acacia plants. Fungal endophytes were isolated from the asymptomatic leaves of A. hindsii plants for further molecular identification of 18S rRNA gene. Inhibitory effects of fungal endophytes were tested against Pseudomonas plant pathogens. Our findings support a potential role of fungal endophytes in pathogen the protection mechanisms against pathogens in myrmecophytic plants and provide the evidence of novel fungal endophytes capable of biosynthesizing bioactive metabolites. PMID- 26843902 TI - Reaching for far-flung antigen: How solid-core podosomes of dendritic cells transform into protrusive structures. AB - We recently identified a novel role for podosomes in antigen sampling. Podosomes are dynamic cellular structures that consist of point-like concentrations of actin surrounded by integrins and adaptor proteins such as vinculin and talin. Podosomes establish cellular contact with the extracellular matrix (ECM) and facilitate cell migration via ECM degradation. In our recent paper, we studied podosomes of human dendritic cells (DCs), major antigen presenting cells (APC) that take-up, process, and present foreign antigen to naive T-cells. We employed gelatin-impregnated porous polycarbonate filters to demonstrate that the mechanosensitive podosomes of DCs selectively localize to regions of low-physical resistance such as the filter pores. After degradation of the gelatin, podosomes increasingly protrude into the lumen of these pores. These protrusive podosome derived structures contain several endocytic and early endosomal markers such as clathrin, Rab5, and VAMP3, and, surprisingly, also contain C-type lectins, a type of pathogen recognition receptors (PRRs). Finally, we performed functional uptake experiments to demonstrate that these PRRs facilitate uptake of antigen from the opposite side of the filter. Our data provide mechanistic insight in how dendritic cells sample for antigen across epithelial barriers for instance from the lumen of the lung and gut. PMID- 26843903 TI - A role for fascin in preventing filopodia breakage in Drosophila tracheal cells. AB - Filopodia are long and thin finger-like protrusions essential for cell migration. They are formed by parallel actin bundles tightly packed by cell type and context dependent actin-bundling proteins. Our recent work analyzing the role of Fascin during tracheal development in Drosophila has shown that Singed (the Drosophila Fascin homolog) acts as a molecular link between the Branchless (FGF)/Breathless (FGFR) pathway and the actin cytoskeleton. We have reported that the lack of Singed (Sn) leads to wavy and flaccid filopodia due to the disorganization of the tracheal actin cytoskeleton. Here we describe for the first time filopodia breakage in Drosophila, and show that Fascin plays a role in this event. We propose that actin filaments in sn mutant filopodia buckle under membrane pressure due to lower bending stiffness, eventually undergoing breakage. Both Filopodia buckling and breakage would impair correct cell navigation and migration. PMID- 26843904 TI - A new V-ATPase regulatory mechanism mediated by the Rab interacting lysosomal protein (RILP). AB - Progressive luminal acidification of intracellular compartments is important for their functions. Proton transport into the organelle's lumen is mediated by vacuolar ATPases (V-ATPases) large multi-subunit proton pumps organized into 2 domains, V0 and V1, working together as a rotary machine. The interaction of each subunit with specific partners plays a crucial role in controlling V-ATPase activity. Recently, we have shown that RILP, a Rab7 effector regulating late endocytic traffic and biogenesis of multivesicular bodies (MVBs), is a specific interactor of the V-ATPase subunit V1G1, a fundamental component of the peripheral stalk for correct V-ATPase assembly. RILP controls V1G1 stability and localization affecting V-ATPase assembly and function at the level of endosomes and lysosomes. The discovery of this new regulatory mechanism for V-ATPase opens new scenario to the comprehension of organelle's pH regulation and reveals a key role of RILP in controlling different aspects of endosome to lysosome transport. PMID- 26843905 TI - Expression of the voltage-sensing phosphatase gene in the chick embryonic tissues and in the adult cerebellum. AB - Voltage-sensing phosphatase (VSP) consists of a transmembrane voltage sensor domain (VSD) and the cytoplasmic domain with phosphoinositide-phosphatase activities. It operates as the voltage sensor and directly translates membrane potential into phosphoinositide turnover by coupling VSD to the cytoplasmic domain. VSPs are evolutionarily conserved from marine invertebrate up to humans. Recently, we demonstrated that ectopic expression of the chick ortholog of VSP, Gg-VSP, in a fibroblast cell line caused characteristic cell process outgrowths. Co-expression of chick PTEN suppressed such morphological change, suggesting that VSP regulates cell shape by increasing PI(3,4)P2. However, the in vivo function of Gg-VSP remains unclear. Here, we showed that in chick embryos Gg-VSP is expressed in the stomach, mesonephros, pharyngeal arch, limb bud, somites, floor plate of neural tube, and notochord. In addition, both Gg-VSP transcripts and the protein were found in the cerebellar Purkinje neurons. These findings provide an insight into the physiological functions of VSP. PMID- 26843906 TI - The Potential Health Benefits of Polyphenol-Rich Extracts from Cichorium intybus L. Studied on Caco-2 Cells Model. AB - Phytochemicals can exert their bioactivity without reaching the systemic circulation; scarcely absorbed antioxidants might reach the large bowel contributing to protection from oxidative damage-induced gastrointestinal diseases. In the present work, we aimed to study the relationship between potential activity of polyphenol-rich extracts from Cichorium intybus L. and changes in morphological characteristics on Caco-2 cells. Phytochemicals content (carotenoids and flavonoids) and total antioxidant activity of Red Chicory of Treviso and Variegated Chicory of Castelfranco were evaluated. The bioactivity of polyphenol-rich extracts from chicories was studied in in vitro Caco-2 cell monolayers model. Morphological characteristics changes to test the antioxidant and/or prooxidant effect were verified by histological analysis and observed by Electronic Scansion Microscopy (SEM). On Caco-2 cell model, the polyphenols fractions from chicories have indicated a moderate antioxidant behavior until 17 MUM concentration, while 70 MUM and 34 MUM exert cytotoxic effects for Treviso's and Castelfranco's Chicory, respectively, highlighted by TEER decreasing, increased permeability, and alteration of epithelium. Our findings support the beneficial effects of these products in counteracting the oxidative stress and cellular damage, induced in vitro on Caco-2 cell model, through interaction with the mucopolysaccharide complexes in the glycocalyx, maintaining in vivo a healthy and effective intestinal barrier. PMID- 26843908 TI - Cell Line-Dependent Variability of Coordinate Expression of p75NTR and CRABP1 and Modulation of Effects of Fenretinide on Neuroblastoma Cells. AB - Neuroblastoma is a childhood neural crest tumor. Fenretinide, a retinoic acid analogue, induces accumulation of mitochondrial reactive oxygen species and consequent apoptosis in neuroblastoma cells. The p75 neurotrophin receptor (p75NTR) enhances the antineuroblastoma cell efficacy of fenretinide in vitro. We examined the role of the retinoid binding protein, CRABP1, in p75NTR-mediated potentiation of the efficacy of fenretinide. Knockdown and overexpression, respectively, of either p75NTR or CRABP1 were effected in neuroblastoma cell lines using standard techniques. Expression was determined by qRT-PCR and confirmed at the protein level by Western blot. Metabolic viability was determined by Alamar blue assay. While protein content of CRABP1 correlated roughly with that of p75NTR in the three neuroblastoid or epithelioid human neuroblastoma cell lines studied, manipulation of p75NTR expression resulted in cell line-dependent, variable change in CRABP1 expression. Furthermore, in some cell lines, induced expression of CRABP1 in the absence of p75NTR did not alter cell sensitivity to fenretinide treatment. The effects of manipulation of p75NTR expression on CRABP1 expression and the effects of CRABP1 expression on fenretinide efficacy are therefore neuroblastoma cell line-dependent. Potentiation of the antineuroblastoma cell effects of fenretinide by p75NTR is not mediated solely through CRABP1. PMID- 26843907 TI - Oxidative Stress in Intracerebral Hemorrhage: Sources, Mechanisms, and Therapeutic Targets. AB - Intracerebral hemorrhage (ICH) is associated with the highest mortality and morbidity despite only constituting approximately 10-15% of all strokes. Complex underlying mechanisms consisting of cytotoxic, excitotoxic, and inflammatory effects of intraparenchymal blood are responsible for its highly damaging effects. Oxidative stress (OS) also plays an important role in brain injury after ICH but attracts less attention than other factors. Increasing evidence has demonstrated that the metabolite axis of hemoglobin-heme-iron is the key contributor to oxidative brain damage after ICH, although other factors, such as neuroinflammation and prooxidases, are involved. This review will discuss the sources, possible molecular mechanisms, and potential therapeutic targets of OS in ICH. PMID- 26843909 TI - Advantages and limits of hemorrhoidal dearterialization in the treatment of symptomatic hemorrhoids. AB - In the last two decades, hemorrhoidal dearterialization has become universally accepted as a treatment option for symptomatic hemorrhoids. The rationale for this procedure is based on the assumption that arterial blood overflow is mainly responsible for dilatation of the hemorrhoidal plexus due to the absence of capillary interposition between the arterial and venous systems within the anal canal. Dearterialization, with either suture ligation (Doppler-guided hemorrhoid artery ligation/transanal hemorrhoidal dearterialization) or laser (hemorrhoidal laser procedure), may be successfully performed alone or with mucopexy. Although the added value of Doppler-guidance in association with dearterialization has recently been challenged, this imaging method still plays an important role in localizing hemorrhoidal arteries and, therefore, minimizing the effect of anatomic variation among patients. However, it is important to employ the correct Doppler transducer. Some Doppler transducers may not easily detect superficial arteries due to inadequate frequency settings. All techniques of dearterialization have the advantage of preserving the anatomy and physiology of the anal canal, when compared to other surgical treatments for hemorrhoids. This advantage cannot be underestimated as impaired anal function, including fecal incontinence and other defecation disorders, may occur following surgical treatment for hemorrhoids. Furthermore, this potentially devastating problem can occur in patients of all ages, including younger patients. PMID- 26843911 TI - Role of frailty and sarcopenia in predicting outcomes among patients undergoing gastrointestinal surgery. AB - According to the United States census bureau 20% of Americans will be older than 65 years in 2030 and half of them will need an operation - equating to about 36 million older surgical patients. Older adults are prone to complications during gastrointestinal cancer treatment and therefore may need to undergo special pretreatment assessments that incorporate frailty and sarcopenia assessments. A focused, structured literature review on PubMed and Google Scholar was performed to identify primary research articles, review articles, as well as practice guidelines on frailty and sarcopenia among patients undergoing gastrointestinal surgery. The initial search identified 450 articles; after eliminating duplicates, reports that did not include surgical patients, case series, as well as case reports, 42 publications on the impact of frailty and/or sarcopenia on outcome of patients undergoing gastrointestinal surgery were included. Frailty is defined as a clinically recognizable state of increased vulnerability to physiologic stressors resulting from aging. Frailty is associated with a decline in physiologic reserve and function across multiple physiologic systems. Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. Unlike cachexia, which is typically associated with weight loss due to chemotherapy or a general malignancy-related cachexia syndrome, sarcopenia relates to muscle mass rather than simply weight. As such, while weight reflects nutritional status, sarcopenia - the loss of muscle mass - is a more accurate and quantitative global marker of frailty. While chronologic age is an important element in assessing a patient's peri-operative risk, physiologic age is a more important determinant of outcomes. Geriatric assessment tools are important components of the pre-operative work-up and can help identify patients who suffer from frailty. Such data are important, as frailty and sarcopenia have repeatedly been demonstrated among the strongest predictors of both short- and long-term outcome following complicated surgical procedures such as esophageal, gastric, colorectal, and hepato-pancreatico-biliary resections. PMID- 26843910 TI - Laparoscopic liver resection: Experience based guidelines. AB - Laparoscopic liver resection (LLR) has been progressively developed along the past two decades. Despite initial skepticism, improved operative results made laparoscopic approach incorporated to surgical practice and operations increased in frequency and complexity. Evidence supporting LLR comes from case-series, comparative studies and meta-analysis. Despite lack of level 1 evidence, the body of literature is stronger and existing data confirms the safety, feasibility and benefits of laparoscopic approach when compared to open resection. Indications for LLR do not differ from those for open surgery. They include benign and malignant (both primary and metastatic) tumors and living donor liver harvesting. Currently, resection of lesions located on anterolateral segments and left lateral sectionectomy are performed systematically by laparoscopy in hepatobiliary specialized centers. Resection of lesions located on posterosuperior segments (1, 4a, 7, 8) and major liver resections were shown to be feasible but remain technically demanding procedures, which should be reserved to experienced surgeons. Hand-assisted and laparoscopy-assisted procedures appeared to increase the indications of minimally invasive liver surgery and are useful strategies applied to difficult and major resections. LLR proved to be safe for malignant lesions and offers some short-term advantages over open resection. Oncological results including resection margin status and long-term survival were not inferior to open resection. At present, surgical community expects high quality studies to base the already perceived better outcomes achieved by laparoscopy in major centers' practice. Continuous surgical training, as well as new technologies should augment the application of laparoscopic liver surgery. Future applicability of new technologies such as robot assistance and image-guided surgery is still under investigation. PMID- 26843912 TI - Anal cancer and intraepithelial neoplasia screening: A review. AB - This review focuses on the early diagnosis of anal cancer and its precursor lesions through routine screening. A number of risk-stratification strategies as well as screening techniques have been suggested, and currently little consensus exists among national societies. Much of the current clinical rationale for the prevention of anal cancer derives from the similar tumor biology of cervical cancer and the successful use of routine screening to identify cervical cancer and its precursors early in the disease process. It is thought that such a strategy of identifying early anal intraepithelial neoplasia will reduce the incidence of invasive anal cancer. The low prevalence of anal cancer in the general population prevents the use of routine screening. However, routine screening of selected populations has been shown to be a more promising strategy. Potential screening modalities include digital anorectal exam, anal Papanicolaou testing, human papilloma virus co-testing, and high-resolution anoscopy. Additional research associating high-grade dysplasia treatment with anal cancer prevention as well as direct comparisons of screening regimens is necessary to develop further anal cancer screening recommendations. PMID- 26843913 TI - Esophageal surgery in minimally invasive era. AB - The widespread popularity of new surgical technologies such as laparoscopy, thoracoscopy and robotics has led many surgeons to treat esophageal diseases with these methods. The expected benefits of minimally invasive surgery (MIS) mainly include reductions of postoperative complications, length of hospital stay, and pain and better cosmetic results. All of these benefits could potentially be of great interest when dealing with the esophagus due to the potentially severe complications that can occur after conventional surgery. Moreover, robotic platforms are expected to reduce many of the difficulties encountered during advanced laparoscopic and thoracoscopic procedures such as anastomotic reconstructions, accurate lymphadenectomies, and vascular sutures. Almost all esophageal diseases are approachable in a minimally invasive way, including diverticula, gastro-esophageal reflux disease, achalasia, perforations and cancer. Nevertheless, while the limits of MIS for benign esophageal diseases are mainly technical issues and costs, oncologic outcomes remain the cornerstone of any procedure to cure malignancies, for which the long-term results are critical. Furthermore, many of the minimally invasive esophageal operations should be compared to pharmacologic interventions and advanced pure endoscopic procedures; such a comparison requires a difficult literature analysis and leads to some confounding results of clinical trials. This review aims to examine the evidence for the use of MIS in both malignancies and more common benign disease of the esophagus, with a particular emphasis on future developments and ongoing areas of research. PMID- 26843915 TI - Gastroesophageal reflux disease: A review of surgical decision making. AB - Gastroesophageal reflux disease (GERD) is a very common disorder with increasing prevalence. It is estimated that up to 20%-25% of Americans experience symptoms of GERD weekly. Excessive reflux of acidic often with alkaline bile salt gastric and duodenal contents results in a multitude of symptoms for the patient including heartburn, regurgitation, cough, and dysphagia. There are also associated complications of GERD including erosive esophagitis, Barrett's esophagus, stricture and adenocarcinoma of the esophagus. While first line treatments for GERD involve mainly lifestyle and non-surgical therapies, surgical interventions have proven to be effective in appropriate circumstances. Anti reflux operations are aimed at creating an effective barrier to reflux at the gastroesophageal junction and thus attempt to improve physiologic and mechanical issues that may be involved in the pathogenesis of GERD. The decision for surgical intervention in the treatment of GERD, moreover, requires an objective confirmation of the diagnosis. Confirmation is achieved using various preoperative evaluations including: ambulatory pH monitoring, esophageal manometry, upper endoscopy (esophagogastroduodenoscopy) and barium swallow. Upon confirmation of the diagnosis and with appropriate patient criteria met, an anti reflux operation is a good alternative to prolonged medical therapy. Currently, minimally invasive gastro-esophageal fundoplication is the gold standard for surgical intervention of GERD. Our review outlines the many factors that are involved in surgical decision-making. We will review the prominent features that reflect appropriate anti-reflux surgery and present suggestions that are pertinent to surgical practices, based on evidence-based studies. PMID- 26843916 TI - How to decide on stent insertion or surgery in colorectal obstruction? AB - Colorectal cancer is one of the most common cancers in western society and malignant obstruction of the colon accounts for 8%-29% of all large bowel obstructions. Conventional treatment of these patients with malignant obstruction requiring urgent surgery is associated with a greater physiological insult on already nutritionally replete patients. Of late the utility of colonic stents has offered an option in the management of these patients in both the palliative and bridge to surgery setting. This has been the subject of many reviews which highlight its efficacy, particulary in reducing ostomy rates, allowing quicker return to oral diet, minimising extended post-operative recovery as well as some quality of life benefits. The uncertainity in managing patients with malignant colonic obstructions has lead to a more cautious use of stenting technology as community equipoise exists. Decision making analysis has demonstrated that surgeons' favored the use of stents in the palliative setting preferentially when compared to the curative setting where surgery was preferred. We aim to review the literature regarding the use of stent or surgery in colorectal obstruction, and then provide a discourse with regards to the approach in synthesising the data and applying it when deciding the appropriate application of stent or surgery in colorectal obstruction. PMID- 26843914 TI - Gallstone ileus, clinical presentation, diagnostic and treatment approach. AB - Gallstone ileus is a mechanical intestinal obstruction due to gallstone impaction within the gastrointestinal tract. Less than 1% of cases of intestinal obstruction are derived from this etiology. The symptoms and signs of gallstone ileus are mostly nonspecific. This entity has been observed with a higher frequency among the elderly, the majority of which have concomitant medical illness. Cardiovascular, pulmonary, and metabolic diseases should be considered as they may affect the prognosis. Surgical relief of gastrointestinal obstruction remains the mainstay of operative treatment. The current surgical procedures are: (1) simple enterolithotomy; (2) enterolithotomy, cholecystectomy and fistula closure (one-stage procedure); and (3) enterolithotomy with cholecystectomy performed later (two-stage procedure). Bowel resection is necessary in certain cases after enterolithotomy is performed. Large prospective laparoscopic and endoscopic trials are expected. PMID- 26843917 TI - Lymphatic spreading and lymphadenectomy for esophageal carcinoma. AB - Esophageal carcinoma (EC) is a highly lethal malignancy with a poor prognosis. One of the most important prognostic factors in EC is lymph node status. Therefore, lymphadenectomy has been recognized as a key that influences the outcome of surgical treatment for EC. However, the lymphatic drainage system of the esophagus, including an abundant lymph-capillary network in the lamina propria and muscularis mucosa, is very complex with cervical, mediastinal and celiac node spreading. The extent of lymphadenectomy for EC has always been controversial because of the very complex pattern of lymph node spreading. In this article, published literature regarding lymphatic spreading was reviewed and the current lymphadenectomy trends for EC are discussed. PMID- 26843918 TI - Single-incision laparoscopic surgery for colorectal cancer. AB - AIM: To determine the effect of single-incision laparoscopic colectomy (SILC) for colorectal cancer on short-term clinical and oncological outcomes by comparison with multiport conventional laparoscopic colectomy (CLC). METHODS: A systematic review was performed using MEDLINE for the time period of 2008 to December 2014 to retrieve all relevant literature. The search terms were "laparoscopy", "single incision", "single port", "single site", "SILS", "LESS" and "colorectal cancer". Publications were included if they were randomized controlled trials, case matched controlled studies, or comparative studies, in which patients underwent single-incision (SILS or LESS) laparoscopic colorectal surgery. Studies were excluded if they were non-comparative, or not including surgery involving the colon or rectum. A total of 15 studies with 589 patients who underwent SILC for colorectal cancer were selected. RESULTS: No significant differences between the groups were noted in terms of mortality or morbidity. The benefit of the SILC approach included reduction in conversion rate to laparotomy, but there were no significant differences in other short-term clinical outcomes between the groups. Satisfactory oncological surgical quality was also demonstrated for SILC for the treatment of colorectal cancer with a similar average lymph node harvest and proximal and distal resection margin length as multiport CLC. CONCLUSION: SILC can be performed safely with similar short-term clinical and oncological outcomes as multiport CLC. PMID- 26843919 TI - Successful living donor intestinal transplantation in cross-match positive recipients: Initial experience. AB - Sensitized patients tend to have longer waiting times on the deceased donor list and are at increased risk of graft loss from acute or chronic rejection compared to non-sensitized candidates. Desensitization protocols are utilized to decrease the levels of alloantibodies and to convert an initial positive cross-match to prospective donors into a negative crossmatch. These procedures are mostly available in the setting of living donation. Due to the elective nature of the procedure, desensitization protocols can be extended until the desire result is obtained prior to transplantation. We present two cases of successful desensitization protocol applied to living donor intestinal transplant candidates that converted to negative cross-match to their donors. We present two cases of intestinal transplant candidates with a potential living donor to whom they are sensitized. Both cases underwent successful transplantation after desensitization protocol. No evidence of humoral rejection has occurred in either recipient. Living donor intestinal transplantation in sensitized recipients against the prospective donors provides the ability to implement a desensitization protocol to convert to negative cross-match. PMID- 26843920 TI - Erratum to: Cytoplasm-predominant Pten associates with increased region-specific brain tyrosine hydroxylase and dopamine D2 receptors in mouse model with autistic traits. AB - [This corrects the article DOI: 10.1186/s13229-015-0056-6.]. PMID- 26843921 TI - Identification of pyrazine-based TrkA inhibitors: design, synthesis, evaluation, and computational modeling studies. AB - Trk receptors play a key role in the development and maintenance of neuronal networks. Recent evidence suggests that the Trk family, specifically TrkA, is an important driver for tumour growth, inflammatory and neuropathic pain, and chemoresistance. Through a computational screen, a novel Trk active pharmacophore was identified and a series of pyrazine-based inhibitors were developed, which potently inhibited TrkA. Inhibitors displayed the highest activity on TrkA when screened against a small, tyrosine kinase panel and also exhibited a non-linear SAR. Predicted binding modes of the inhibitors were examined, which identified exploitable regions for future development of more advanced inhibitors. PMID- 26843922 TI - The protective or damaging effect of Tumor necrosis factor-alpha in acute liver injury is concentration-dependent. AB - BACKGROUND: Inflammatory cytokine is important in modulating injured diseases. Tumor necrosis factor-alpha (TNF-alpha), one of potent inflammatory cytokines, plays a dominant role in host defense reaction. However, the concrete effect of TNF-alpha on acute liver injury is totally unclear. Here we reported the concrete effect and possible mechanisms of TNF-alpha on acute liver injury induced by carbon tetrachloride (CCl4). METHODS: SD male rats were equally divided into nine groups. CCl4 (1 ml/kg) was subcutaneously injected into the rats. Enbrel, a TNF alpha inhibitor, were intraperitoneally injected at dose of 0, 0.25, 0.5, 1, 2, 4 or 8 mg/kg 15 min before the CCl4 injection. 24 h later, rats were sacrificed. Serum ALT and AST were measured with an autoanalyzer. Serum TNF-alpha were measured by ELISA. HE staining was used to observe the liver tissue morphology. Hepatocellular apoptosis were tested by immunochemistry and Tunnel kit. Inflammatory factors, involve IL-4, IL-6, IL-8, IL-beta and IFN-gamma were detected by RT-PCR. The NF-kappaB signal pathway and anti-apoptotic genes include Bcl-XL, FHC, XIAP and Bcl-2 were measured by western-blotting and RT-PCR. RESULTS: The change of liver function presented an obvious "V" shape in the whole process of persistently increased Enbrel. As Enbrel was increased gradually from 0 to 1 mg/kg, serum TNF-alpha were blocked, ALT and AST were gradually decreased as TNF-alpha as well as the numbers of hepatocellular apoptosis, and were declined to the minimum at 1 mg/kg Enbrel. As Enbrel was increased gradually from 1 to 8 mg/kg, ALT, AST and hepatocellular apoptosis were increased instead, and reached to the maximum at 8 mg/kg Enbrel. HE showed that the seriousness of hepatocellular steatosis was the most at 8 mg/kg Enbrel, and second at 0 mg/kg, the weakest at 1 mg/kg in the acute liver injury. Western-blotting and RT-PCR showed NF-kappaB, p-IkappaBalpha and antiapoptotic genes include Bcl-XL, FHC, XIAP, Bcl-2 were decreased as TNF-alpha was blocked by increased Enbrel. CONCLUSION: Our results suggested that TNF-alpha had a dual role in acute liver injury. It was regulated might via the corporate effect of NF-kappaB signal pawahway and anti-apoptosis. Meanwhile, our findings provide a reference for clinical treatment of acute liver injury. PMID- 26843923 TI - Loss of genetic integrity and biological invasions result from stocking and introductions of Barbus barbus: insights from rivers in England. AB - Anthropogenic activities, including the intentional releases of fish for enhancing populations (stocking), are recognized as adversely impacting the adaptive potential of wild populations. Here, the genetic characteristics of European barbel Barbus barbus were investigated using 18 populations in England, where it is indigenous to eastern-flowing rivers and where stocking has been used to enhance these populations. Invasive populations are also present in western flowing rivers following introductions of translocated fish. Two genetic clusters were evident in the indigenous range, centered on catchments in northeast and southeast England. However, stocking activities, including the release of hatchery-reared fish, have significantly reduced the genetic differentiation across the majority of this range. In addition, in smaller indigenous rivers, populations appeared to mainly comprise fish of hatchery origin. In the nonindigenous range, genetic data largely aligned to historical stocking records, corroborating information that one particular river (Kennet) in southeast England was the original source of most invasive B. barbus in England. It is recommended that these genetic outputs inform management measures to either restore or maintain the original genetic diversity of the indigenous rivers, as this should help ensure populations can maintain their ability to adapt to changing environmental conditions. Where stocking is considered necessary, it is recommended that only broodstock from within the catchment is used. PMID- 26843925 TI - Assessing models of speciation under different biogeographic scenarios; an empirical study using multi-locus and RNA-seq analyses. AB - Evolutionary biology often seeks to decipher the drivers of speciation, and much debate persists over the relative importance of isolation and gene flow in the formation of new species. Genetic studies of closely related species can assess if gene flow was present during speciation, because signatures of past introgression often persist in the genome. We test hypotheses on which mechanisms of speciation drove diversity among three distinct lineages of desert tortoise in the genus Gopherus. These lineages offer a powerful system to study speciation, because different biogeographic patterns (physical vs. ecological segregation) are observed at opposing ends of their distributions. We use 82 samples collected from 38 sites, representing the entire species' distribution and generate sequence data for mtDNA and four nuclear loci. A multilocus phylogenetic analysis in *BEAST estimates the species tree. RNA-seq data yield 20,126 synonymous variants from 7665 contigs from two individuals of each of the three lineages. Analyses of these data using the demographic inference package ?a?i serve to test the null hypothesis of no gene flow during divergence. The best-fit demographic model for the three taxa is concordant with the *BEAST species tree, and the ?a?i analysis does not indicate gene flow among any of the three lineages during their divergence. These analyses suggest that divergence among the lineages occurred in the absence of gene flow and in this scenario the genetic signature of ecological isolation (parapatric model) cannot be differentiated from geographic isolation (allopatric model). PMID- 26843926 TI - Maternal adjustment or constraint: differential effects of food availability on maternal deposition of macro-nutrients, steroids and thyroid hormones in rock pigeon eggs. AB - In oviparous species like birds, eggs provide the direct environment in which embryos are developing. Mothers may adjust different egg components in different ways in reaction to environmental cues either to adjust offspring development or because of constraints. In this study, we investigated the effects of food quality and quantity before and during egg laying on three different aspects of egg quality: macro-nutrients (egg and yolk mass), androgens (testosterone and androstenedione), and thyroid hormones (3,5,3'-triiodothyronine, T3 and l thyroxine, T4), using the rock pigeon (Columba livia). As expected, egg and yolk mass were significantly reduced for the eggs laid under the poor-food condition, indicating a maternal trade-off between offspring and self in allocating important resources. We did not find any significant change in yolk testosterone or their within-clutch pattern over the laying sequence. This is consistent with the fact that, in contrast with nutrients, these hormones are not costly to produce, but does not support the hypothesis that they play a role in adjusting brood size to food conditions. In contrast, we found that T3 levels were higher in the egg yolks under the poor-food condition whereas the total T4 content was lower. This change could be related to the fact that iodine, the critical constituent of thyroid hormones, might be a limiting factor in the production of this hormone. Given the knowledge that food restriction usually lead to reduction of circulating T3 levels, our results suggested that avian mothers can independently regulate its concentrations in their eggs from their own circulation. The study demonstrates that environmentally induced maternal effects via the egg can be a result of a combination of constrained resources and unconstrained signals and that thyroid hormones might be an interesting case of both. Therefore, this hormone and the interplay of different maternal effects on the offspring phenotype deserve much more attention. PMID- 26843927 TI - Inter-assemblage facilitation: the functional diversity of cavity-producing beetles drives the size diversity of cavity-nesting bees. AB - Inter-specific interactions are important drivers and maintainers of biodiversity. Compared to trophic and competitive interactions, the role of non trophic facilitation among species has received less attention. Cavity-nesting bees nest in old beetle borings in dead wood, with restricted diameters corresponding to the body size of the bee species. The aim of this study was to test the hypothesis that the functional diversity of cavity-producing wood boring beetles - in terms of cavity diameters - drives the size diversity of cavity nesting bees. The invertebrate communities were sampled in 30 sites, located in forested landscapes along an elevational gradient. We regressed the species richness and abundance of cavity nesting bees against the species richness and abundance of wood boring beetles, non-wood boring beetles and elevation. The proportion of cavity nesting bees in bee species assemblage was regressed against the species richness and abundance of wood boring beetles. We also tested the relationships between the size diversity of cavity nesting bees and wood boring beetles. The species richness and abundance of cavity nesting bees increased with the species richness and abundance of wood boring beetles. No such relationship was found for non-wood boring beetles. The abundance of wood boring beetles was also related to an increased proportion of cavity nesting bee individuals. Moreover, the size diversity of cavity-nesting bees increased with the functional diversity of wood boring beetles. Specifically, the mean and dispersion of bee body sizes increased with the functional dispersion of large wood boring beetles. The positive relationships between cavity producing bees and cavity nesting bees suggest that non-trophic facilitative interactions between species assemblages play important roles in organizing bee species assemblages. Considering a community-wide approach may therefore be required if we are to successfully understand and conserve wild bee species assemblages in forested landscapes. PMID- 26843924 TI - Iberian red deer: paraphyletic nature at mtDNA but nuclear markers support its genetic identity. AB - Red deer populations in the Iberian glacial refugium were the main source for postglacial recolonization and subspecific radiation in north-western Europe. However, the phylogenetic history of Iberian red deer (Cervus elaphus hispanicus) and its relationships with northern European populations remain uncertain. Here, we study DNA sequences at the mitochondrial control region along with STR markers for over 680 specimens from all the main red deer populations in Spain and other west European areas. Our results from mitochondrial and genomic DNA show contrasting patterns, likely related to the nature of these types of DNA markers and their specific processes of change over time. The results, taken together, bring support to two distinct, cryptic maternal lineages for Iberian red deer that predated the last glacial maximum and that have maintained geographically well differentiated until present. Haplotype relationships show that only one of them contributed to the northern postglacial recolonization. However, allele frequencies of nuclear markers evidenced one main differentiation between Iberian and northern European subspecies although also supported the structure of both matrilines within Iberia. Thus, our findings reveal a paraphyletic nature for Iberian red deer but also its genetic identity and differentiation with respect to northern subspecies. Finally, we suggest that maintaining the singularity of Iberian red deer requires preventing not only restocking practices with red deer specimens belonging to other European populations but also translocations between both Iberian lineages. PMID- 26843928 TI - Genetic variation and population structure in a threatened species, the Utah prairie dog Cynomys parvidens: the use of genetic data to inform conservation actions. AB - The Utah prairie dog (Cynomys parvidens), listed as threatened under the United States Endangered Species Act, was the subject of an extensive eradication program throughout its range during the 20th century. Eradication campaigns, habitat destruction/fragmentation/conversion, and epizootic outbreaks (e.g., sylvatic plague) have reduced prairie dog numbers from an estimated 95,000 individuals in the 1920s to approximately 14,000 (estimated adult spring count) today. As a result of these anthropogenic actions, the species is now found in small isolated sets of subpopulations. We characterized the levels of genetic diversity and population genetic structure using 10 neutral nuclear microsatellite loci for twelve populations (native and transplanted) representative of the three management designated "recovery units," found in three distinct biogeographic regions, sampled across the species' range. The results indicate (1) low levels of genetic diversity within colonies (H e = 0.109 0.357; H o = 0.106- 0.313), (2) high levels of genetic differentiation among colonies (global F ST = 0.296), (3) very small genetic effective population sizes, and (4) evidence of genetic bottlenecks. The genetic data reveal additional subdivision such that colonies within recovery units do not form single genotype clusters consistent with recovery unit boundaries. Genotype cluster membership support historical gene flow among colonies in the easternmost West Desert Recovery Unit with the westernmost Pausaugunt colonies and among the eastern Pausaugunt colonies and the Awapa Recovery unit to the north. In order to maintain the long-term viability of the species, there needs to be an increased focus on maintaining suitable habitat between groups of existing populations that can act as connective corridors. The location of future translocation sites should be located in areas that will maximize connectivity, leading to maintenance of genetic variation and evolutionary potential. PMID- 26843929 TI - Pine invasions in treeless environments: dispersal overruns microsite heterogeneity. AB - Understanding biological invasions patterns and mechanisms is highly needed for forecasting and managing these processes and their negative impacts. At small scales, ecological processes driving plant invasions are expected to produce a spatially explicit pattern driven by propagule pressure and local ground heterogeneity. Our aim was to determine the interplay between the intensity of seed rain, using distance to a mature plantation as a proxy, and microsite heterogeneity in the spreading of Pinus contorta in the treeless Patagonian steppe. Three one-hectare plots were located under different degrees of P. contorta invasion (Coyhaique Alto, 45 degrees 30'S and 71 degrees 42'W). We fitted three types of inhomogeneous Poisson models to each pine plot in an attempt for describing the observed pattern as accurately as possible: the "dispersal" models, "local ground heterogeneity" models, and "combined" models, using both types of covariates. To include the temporal axis in the invasion process, we analyzed both the pattern of young and old recruits and also of all recruits together. As hypothesized, the spatial patterns of recruited pines showed coarse scale heterogeneity. Early pine invasion spatial patterns in our Patagonian steppe site is not different from expectations of inhomogeneous Poisson processes taking into consideration a linear and negative dependency of pine recruit intensity on the distance to afforestations. Models including ground cover predictors were able to describe the point pattern process only in a couple of cases but never better than dispersal models. This finding concurs with the idea that early invasions depend more on seed pressure than on the biotic and abiotic relationships seed and seedlings establish at the microsite scale. Our results show that without a timely and active management, P. contorta will invade the Patagonian steppe independently of the local ground-cover conditions. PMID- 26843930 TI - Influence of geography and environment on patterns of genetic differentiation in a widespread submerged macrophyte, Eurasian watermilfoil (Myriophyllum spicatum L., Haloragaceae). AB - The effects of geographic and environmental variables on the pattern of genetic differentiation have been thoroughly studied, whereas empirical studies on aquatic plants are rare. We examined the spatial genetic differentiation of 58 Myriophyllum spicatum populations distributed throughout China with 12 microsatellite loci, and we analyzed its association with geographic distance, geographic barriers, and environmental dissimilarity using causal modeling and multiple matrix regression with randomization (MMRR) analysis. Two genetic clusters were identified, and their geographic distribution suggested mountain ranges as a barrier to gene flow. The causal modeling revealed that both climate and geographic barriers significantly influenced genetic divergence among M. spicatum populations and that climate had the highest regression coefficient according to the MMRR analysis. This study showed that geography and environment together played roles in shaping the genetic structure of M. spicatum and that the influence of environment was greater. Our findings emphasized the potential importance of the environment in producing population genetic differentiation in aquatic plants at a large geographic scale. PMID- 26843931 TI - Phylogenetic analysis suggests that sociality is associated with reduced effectiveness of selection. AB - The evolution of sociality in spiders is associated with female bias, reproductive skew and an inbreeding mating system, factors that cause a reduction in effective population size and increase effects of genetic drift. These factors act to decrease the effectiveness of selection, thereby increasing the fixation probability of deleterious mutations. Comparative studies of closely related species with contrasting social traits and mating systems provide the opportunity to test consequences of low effective population size on the effectiveness of selection empirically. We used phylogenetic analyses of three inbred social spider species and seven outcrossing subsocial species of the genus Stegodyphus, and compared dN/dS ratios and codon usage bias between social Inbreeding and subsocial outcrossing mating systems to assess the effectiveness of selection. The overall results do not differ significantly between the social inbreeding and outcrossing species, but suggest a tendency for lower codon usage bias and higher dN/dS ratios in the social inbreeding species compared with their outcrossing congeners. The differences in dN/dS ratio and codon usage bias between social and subsocial species are modest but consistent with theoretical expectations of reduced effectiveness of selection in species with relatively low effective population size. The modest differences are consistent with relatively recent evolution of social mating systems. Additionally, the short terminal branches and lack of speciation of the social lineages, together with low genetic diversity lend support for the transient state of permanent sociality in spiders. PMID- 26843932 TI - Quantitative and qualitative shifts in defensive metabolites define chemical defense investment during leaf development in Inga, a genus of tropical trees. AB - Selective pressures imposed by herbivores are often positively correlated with investments that plants make in defense. Research based on the framework of an evolutionary arms race has improved our understanding of why the amount and types of defenses differ between plant species. However, plant species are exposed to different selective pressures during the life of a leaf, such that expanding leaves suffer more damage from herbivores and pathogens than mature leaves. We hypothesize that this differential selective pressure may result in contrasting quantitative and qualitative defense investment in plants exposed to natural selective pressures in the field. To characterize shifts in chemical defenses, we chose six species of Inga, a speciose Neotropical tree genus. Focal species represent diverse chemical, morphological, and developmental defense traits and were collected from a single site in the Amazonian rainforest. Chemical defenses were measured gravimetrically and by characterizing the metabolome of expanding and mature leaves. Quantitative investment in phenolics plus saponins, the major classes of chemical defenses identified in Inga, was greater for expanding than mature leaves (46% and 24% of dry weight, respectively). This supports the theory that, because expanding leaves are under greater selective pressure from herbivores, they rely more upon chemical defense as an antiherbivore strategy than do mature leaves. Qualitatively, mature and expanding leaves were distinct and mature leaves contained more total and unique metabolites. Intraspecific variation was greater for mature leaves than expanding leaves, suggesting that leaf development is canalized. This study provides a snapshot of chemical defense investment in a speciose genus of tropical trees during the short, few-week period of leaf development. Exploring the metabolome through quantitative and qualitative profiling enables a more comprehensive examination of foliar chemical defense investment. PMID- 26843933 TI - Context-dependent female preference for multiple ornaments in the bearded reedling. AB - While it is well established that females prefer to mate with well-ornamented males, the influence of perceptive and cognitive processes on the expression of female mate choice is still poorly known. It has been suggested that the female perception of a male's attractiveness is not absolute, but depends on the other males with which he is compared that have been previously encountered (comparative evaluation). We investigated whether mate preference in bearded reedlings (Panurus biarmicus) is dependent on or independent of social context in relation to two different traits: beard and tail lengths. Each female had a choice between two to three males with different modifications of beard and tail. For each female, three different experiments were conducted (one binary and two trinary tests). We found that when females are presented with options that vary antagonistically with respect to two ornaments (binary test), some individuals prefer one trait while others the other trait. This indicates that in our bearded reedlings population exists a mate preference polymorphisms. Moreover, we found that the presence of a third stimulus, irrespective of the initial preference, reduced the strength of the initial preference - what we can call a "preference dilution effect." Our results suggest that the female's choice may be constrained by her cognitive abilities when she is simultaneously presented with several options varying for two uncorrelated traits. PMID- 26843934 TI - When can we measure stress noninvasively? Postdeposition effects on a fecal stress metric confound a multiregional assessment. AB - Measurement of stress hormone metabolites in fecal samples has become a common method to assess physiological stress in wildlife populations. Glucocorticoid metabolite (GCM) measurements can be collected noninvasively, and studies relating this stress metric to anthropogenic disturbance are increasing. However, environmental characteristics (e.g., temperature) can alter measured GCM concentration when fecal samples cannot be collected immediately after defecation. This effect can confound efforts to separate environmental factors causing predeposition physiological stress in an individual from those acting on a fecal sample postdeposition. We used fecal samples from American pikas (Ochotona princeps) to examine the influence of environmental conditions on GCM concentration by (1) comparing GCM concentration measured in freshly collected control samples to those placed in natural habitats for timed exposure, and (2) relating GCM concentration in samples collected noninvasively throughout the western United States to local environmental characteristics measured before and after deposition. Our timed-exposure trials clarified the spatial scale at which exposure to environmental factors postdeposition influences GCM concentration in pika feces. Also, fecal samples collected from occupied pika habitats throughout the species' range revealed significant relationships between GCM and metrics of climate during the postdeposition period (maximum temperature, minimum temperature, and precipitation during the month of sample collection). Conversely, we found no such relationships between GCM and metrics of climate during the predeposition period (prior to the month of sample collection). Together, these results indicate that noninvasive measurement of physiological stress in pikas across the western US may be confounded by climatic conditions in the postdeposition environment when samples cannot be collected immediately after defecation. Our results reiterate the importance of considering postdeposition environmental influences on this stress metric, especially in multiregional comparisons. However, measurements of fecal GCM concentration should prove useful for population monitoring within an eco-region or when postdeposition exposure can be minimized. PMID- 26843935 TI - The influence of simulated exploitation on Patella vulgata populations: protandric sex change is size-dependent. AB - Grazing mollusks are used as a food resource worldwide, and limpets are harvested commercially for both local consumption and export in several countries. This study describes a field experiment to assess the effects of simulated human exploitation of limpets Patella vulgata on their population ecology in terms of protandry (age-related sex change from male to female), growth, recruitment, migration, and density regulation. Limpet populations at two locations in southwest England were artificially exploited by systematic removal of the largest individuals for 18 months in plots assigned to three treatments at each site: no (control), low, and high exploitation. The shell size at sex change (L 50: the size at which there is a 50:50 sex ratio) decreased in response to the exploitation treatments, as did the mean shell size of sexual stages. Size dependent sex change was indicated by L 50 occurring at smaller sizes in treatments than controls, suggesting an earlier switch to females. Mean shell size of P. vulgata neuters changed little under different levels of exploitation, while males and females both decreased markedly in size with exploitation. No differences were detected in the relative abundances of sexual stages, indicating some compensation for the removal of the bigger individuals via recruitment and sex change as no migratory patterns were detected between treatments. At the end of the experiment, 0-15 mm recruits were more abundant at one of the locations but no differences were detected between treatments. We conclude that sex change in P. vulgata can be induced at smaller sizes by reductions in density of the largest individuals reducing interage class competition. Knowledge of sex-change adaptation in exploited limpet populations should underpin strategies to counteract population decline and improve rocky shore conservation and resource management. PMID- 26843936 TI - Mapping species abundance by a spatial zero-inflated Poisson model: a case study in the Wadden Sea, the Netherlands. AB - The objective of the study was to provide a general procedure for mapping species abundance when data are zero-inflated and spatially correlated counts. The bivalve species Macoma balthica was observed on a 500*500 m grid in the Dutch part of the Wadden Sea. In total, 66% of the 3451 counts were zeros. A zero inflated Poisson mixture model was used to relate counts to environmental covariates. Two models were considered, one with relatively fewer covariates (model "small") than the other (model "large"). The models contained two processes: a Bernoulli (species prevalence) and a Poisson (species intensity, when the Bernoulli process predicts presence). The model was used to make predictions for sites where only environmental data are available. Predicted prevalences and intensities show that the model "small" predicts lower mean prevalence and higher mean intensity, than the model "large". Yet, the product of prevalence and intensity, which might be called the unconditional intensity, is very similar. Cross-validation showed that the model "small" performed slightly better, but the difference was small. The proposed methodology might be generally applicable, but is computer intensive. PMID- 26843937 TI - Exclusion of introduced deer increases size and seed production success in an island-endemic plant species. AB - The presence of extra-local invaders, such as the southern California mule deer (Odocoileus hemionus) on Santa Catalina Island, may contribute to more selective and insidious effects within the unique ecosystems that have evolved in their absence. Studies at the species level may detect effects not noticed in broader, community level vegetation monitoring or help tease apart differences in the level of effect among the various ecological components of an invaded system. In this initial study, we measured the impacts of herbivory by mule deer, a species native to analogous habitats on the adjacent mainland, on size and seed production success for Crocanthemum greenei (island rush-rose), a federally listed sub-shrub that is not present on mainland California. We found deer exclusion resulted in an overall increase in stem measurement of 18.8 cm. Exclosure populations exhibited complete seed production success, whereas control populations showed significantly reduced success and exhibited complete failure within 58% of populations. These results show that the introduced mule deer on Santa Catalina Island are negatively affecting a federally threatened plant species. This strongly implies that the current deer management strategy is insufficient, if one of its goals is biodiversity and endemic species conservation. PMID- 26843938 TI - Effects of food variability on growth and reproduction of Aedes aegypti. AB - Despite a large body of knowledge about the evolution of life histories, we know little about how variable food availability during an individual's development affects its life history. We measured the effects of manipulating food levels during early and late larval development of the mosquito Aedes aegypti on its growth rate, life history and reproductive success. Switching from low to high food led to compensatory growth: individuals grew more rapidly during late larval development and emerged at a size close to that of mosquitoes consistently reared at high food. However, switching to high food had very little effect on longevity, and fecundity and reproductive success were considerably lower than in consistently well-fed mosquitoes. Changing from high to low food led to adults with similar size as in consistently badly nourished mosquitoes, but even lower fecundity and reproductive success. A rapid response of growth to changing resources can thus have unexpected effects in later life and in lifetime reproductive success. More generally, our study emphasizes the importance of varying developmental conditions for the evolutionary pressures underlying life history evolution. PMID- 26843939 TI - Symbiodinium clades A and D differentially predispose Acropora cytherea to disease and Vibrio spp. colonization. AB - Coral disease outbreaks have increased over the last three decades, but their causal agents remain mostly unclear (e.g., bacteria, viruses, fungi, protists). This study details a 14-month-long survey of coral colonies in which observations of the development of disease was observed in nearly half of the sampled colonies. A bimonthly qPCR method was used to quantitatively and qualitatively evaluate Symbiodinium assemblages of tagged colonies, and to detect the presence of Vibrio spp. Firstly, our data showed that predisposition to disease development in general, and, more specifically, infection by Vibrio spp. in Acropora cytherea depended on which clades of Symbiodinium were harbored. In both cases, harboring clade D rather than A was beneficial to the coral host. Secondly, the detection of Vibrio spp. in only colonies that developed disease strongly suggests opportunistic traits of the bacteria. Finally, even if sporadic cases of switching and probably shuffling were observed, this long-term survey does not suggest specific-clade recruitment in response to stressors. Altogether, our results demonstrate that the fitness of the coral holobiont depends on its initial consortium of Symbiodinium, which is distinct among colonies, rather than a temporary adaptation achieved through acquiring different Symbiodinium clades. PMID- 26843940 TI - How fast is fast? Eco-evolutionary dynamics and rates of change in populations and phenotypes. AB - It is increasingly recognized that evolution may occur in ecological time. It is not clear, however, how fast evolution - or phenotypic change more generally - may be in comparison with the associated ecology, or whether systems with fast ecological dynamics generally have relatively fast rates of phenotypic change. We developed a new dataset on standardized rates of change in population size and phenotypic traits for a wide range of species and taxonomic groups. We show that rates of change in phenotypes are generally no more than 2/3, and on average about 1/4, the concurrent rates of change in population size. There was no relationship between rates of population change and rates of phenotypic change across systems. We also found that the variance of both phenotypic and ecological rates increased with the mean across studies following a power law with an exponent of two, while temporal variation in phenotypic rates was lower than in ecological rates. Our results are consistent with the view that ecology and evolution may occur at similar time scales, but clarify that only rarely do populations change as fast in traits as they do in abundance. PMID- 26843941 TI - Mean reproductive traits of fungal assemblages are correlated with resource availability. AB - Organisms have evolved a fascinating variety of strategies and organs for successful reproduction. Fruit bodies are the reproductive organ of fungi and vary considerably in size and shape among species. Our understanding of the mechanisms underlying the differences in fruit body size among species is still limited. Fruit bodies of saprotrophic fungi are smaller than those of mutualistic ectomycorrhizal fungi. If differences in fruit body size are determined by carbon acquisition, then mean reproductive traits of saprotrophic and ectomycorrhizal fungi assemblages should vary differently along gradients of resource availability as carbon acquisition seems more unpredictable and costly for saprotrophs than for ectomycorrhizal fungi. Here, we used 48 local inventories of fungal fruit bodies (plot size: 0.02 ha each) sampled along a gradient of resource availability (growing stock) across 3 years in the Bavarian Forest National Park in Germany to investigate regional and local factors that might influence the distribution of species with different reproductive traits, particularly fruit body size. As predicted, mean fruit body size of local assemblages of saprotrophic fungi was smaller than expected from the distribution of traits of the regional species pool across central and northern Europe, whereas that of ectomycorrhizal fungi did not differ from random expectation. Furthermore and also as expected, mean fruit body size of assemblages of saprotrophic fungi was significantly smaller than for assemblages of ectomycorrhizal species. However, mean fruit body sizes of not only saprotrophic species but also ectomycorrhizal species increased with resource availability, and the mean number of fruit bodies of both assemblages decreased. Our results indicate that the differences in carbon acquisition between saprotrophs and ectomycorrhizal species lead to differences in basic reproductive strategies, with implications for the breadth of their distribution. However, the differences in resource acquisition cannot explain detailed species distribution patterns at a finer, local scale based on their reproductive traits. PMID- 26843942 TI - Utility of internally transcribed spacer region of rDNA (ITS) and beta-tubulin gene sequences to infer genetic diversity and migration patterns of Colletotrichum truncatum infecting Capsicum spp. AB - Anthracnose is among the most economically important diseases affecting pepper (Capsicum spp.) production in the tropics and subtropics. Of the three species of Colletotrichum implicated as causal agents of pepper anthracnose, C. truncatum is considered to be the most destructive in agro-ecosystems worldwide. However, the genetic variation and the migration potential of C. truncatum infecting pepper are not known. Five populations were selected for study and a two-locus (internally transcribed spacer region, ITS1-5.8S-ITS2, and beta-tubulin, beta TUB) sequence data set was generated and used in the analyses. Sequences of the ITS region were less informative than beta -tubulin gene sequences based on comparisons of DNA polymorphism indices. Trinidad had the highest genetic diversity and also had the largest effective population size in pairwise comparisons with the other populations. The Trinidad population also demonstrated significant genetic differentiation from the other populations. AMOVA and STRUCTURE analyses both suggested significant genetic variation within populations more so than among populations. A consensus Maximum Likelihood tree based on beta-TUB gene sequences revealed very little intraspecific diversity for all isolates except for Trinidad. Two clades consisting solely of Trinidad isolates may have diverged earlier than the other isolates. There was also evidence of directional migration among the five populations. These findings may have a direct impact on the development of integrated disease management strategies to control C. truncatum infection in pepper. PMID- 26843943 TI - Extremely high proportions of male flowers and geographic variation in floral ratios within male figs of Ficus tikoua despite pollinators displaying active pollen collection. AB - Most plants are pollinated passively, but active pollination has evolved among insects that depend on ovule fertilization for larval development. Anther-to ovule ratios (A/O ratios, a coarse indicator of pollen-to-ovule ratios) are strong indicators of pollination mode in fig trees and are consistent within most species. However, unusually high values and high variation of A/O ratios (0.096 10.0) were detected among male plants from 41 natural populations of Ficus tikoua in China. Higher proportions of male (staminate) flowers were associated with a change in their distribution within the figs, from circum-ostiolar to scattered. Plants bearing figs with ostiolar or scattered male flowers were geographically separated, with scattered male flowers found mainly on the Yungui Plateau in the southwest of our sample area. The A/O ratios of most F. tikoua figs were indicative of passive pollination, but its Ceratosolen fig wasp pollinator actively loads pollen into its pollen pockets. Additional pollen was also carried on their body surface and pollinators emerging from scattered-flower figs had more surface pollen. Large amounts of pollen grains on the insects' body surface are usually indicative of a passive pollinator. This is the first recorded case of an actively pollinated Ficus species producing large amounts of pollen. Overall high A/O ratios, particularly in some populations, in combination with actively pollinating pollinators, may reflect a response by the plant to insufficient quantities of pollen transported in the wasps' pollen pockets, together with geographic variation in this pollen limitation. This suggests an unstable scenario that could lead to eventual loss of wasp active pollination behavior. PMID- 26843944 TI - Stoichiometrical regulation of soil organic matter decomposition and its temperature sensitivity. AB - The decomposition of soil organic matter (SOM) can be described by a set of kinetic principles, environmental constraints, and substrate supply. Here, we hypothesized that SOM decomposition rates (R) and its temperature sensitivity (Q 10) would increase steadily with the N:C ratios of added substrates by alleviating N limitation on microbial growth. We tested this hypothesis by investigating SOM decomposition in both grassland and forest soils after addition of substrates with a range of N:C ratios. The results showed that Michaelis Menten equations well fit the response of R to the N:C ratio variations of added substrates, and their coefficients of determination (R (2)) ranged from 0.65 to 0.89 (P < 0.01). Moreover, the maximal R, Q 10, and cumulative C emission of SOM decomposition increased exponentially with the N:C ratios of added substrates, and were controlled interactively by incubation temperature and the N:C ratios of the added substrates. We demonstrated that SOM decomposition rate and temperature sensitivity were exponentially correlated to substrate stoichiometry (N:C ratio) in both grassland and forest soils. Therefore, these correlations should be incorporated into the models for the prediction of SOM decomposition rate under warmer climatic scenarios. PMID- 26834976 TI - Nutrition transition in South Asia: the emergence of non-communicable chronic diseases. AB - OVERVIEW: South Asian countries have experienced a remarkable economic growth during last two decades along with subsequent transformation in social, economic and food systems. Rising disposable income levels continue to drive the nutrition transition characterized by a shift from a traditional high-carbohydrate, low-fat diets towards diets with a lower carbohydrate and higher proportion of saturated fat, sugar and salt. Steered by various transitions in demographic, economic and nutritional terms, South Asian population are experiencing a rapidly changing disease profile. While the healthcare systems have long been striving to disentangle from the vicious cycle of poverty and undernutrition, South Asian countries are now confronted with an emerging epidemic of obesity and a constellation of other non-communicable diseases (NCDs). This dual burden is bringing about a serious health and economic conundrum and is generating enormous pressure on the already overstretched healthcare system of South Asian countries. OBJECTIVES: The Nutrition transition has been a very popular topic in the field of human nutrition during last few decades and many countries and broad geographic regions have been studied. However there is no review on this topic in the context of South Asia as yet. The main purpose of this review is to highlight the factors accounting for the onset of nutrition transition and its subsequent impact on epidemiological transition in five major South Asian countries including Bangladesh, India, Nepal, Pakistan and Sri Lanka. Special emphasis was given on India and Bangladesh as they together account for 94% of the regional population and about half world's malnourished population. METHODS: This study is literature based. Main data sources were published research articles obtained through an electronic medical databases search. PMID- 26834981 TI - Case Report: A case report of unstable Hangman fracture in a eighty year old male. AB - Herein we discuss a rare variant of hangman's fracture in an eighty year old male with good Karnofsky performance score. We performed X-ray and magnetic resonance imaging (MRI) of the cervical spine to confirm the diagnosis. The patient was placed on a gentle cervical traction which showed good reduction. Despite being on a resource limited setup, we performed posterior occipitocervical fusion with bone graft fusion followed by early mobilization. A postoperative scan showed good reduction and purchase of the screws. This case highlights the importance of choosing the correct therapeutic attitude for the management of the geriatric population especially in those who do not have any significant co-morbid conditions. PMID- 26834978 TI - Is MTHFD1 polymorphism rs 2236225 (c.1958G>A) associated with the susceptibility of NSCL/P? A systematic review and meta-analysis. AB - AIMS: To investigate the association between the methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) polymorphism rs 2236225 (c.1958G>A) and susceptibility to non-syndromic cleft of the lip and/or palate (NSCL/P). METHODS: An extensive literature review has been conducted using PubMed, Web of Science, Cochrane Library, Google Scholar, the China National Knowledge Infrastructure (CNKI), and Wanfang Database for eligible researches. The terms for searching were "cleft lip OR cleft palate OR CLP OR CL/P OR oral facial cleft OR OFC" AND "methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 OR methenyltetrahydrofolate cyclohydrolase formyltetrahydrofolate synthetase OR MTHFD1 OR MTHFD". Two independent researchers screened, evaluated and extracted the data of included studies. The pooled odds ratios (OR) with 95% confidence intervals (95% CI) were calculated by random effects model under five gene models. Subgroup, sensitivity analysis and publication bias were also assessed. RESULTS: Ten case-control studies have been included in the systematic review and eight studies have been considered for the meta-analysis. Overall, the MTHFD1 polymorphism rs2236225 and the risk of NSCL/P showed pooled OR (95% CI) of 1.02 (0.86-1.21) under allelic model. A higher degree of heterogeneity was observed in Asian countries (I (2) = 75.6%) compared to non-Asian countries (I (2) = 48.9%). Similar consequence appeared in the subgroup of children (I (2) = 78.6%) compared with that of mothers (I (2) = 0.0%). There was no significant difference in the publication bias by the Begg's funnel plot (P = 0.711) and Egger's regression test (P = 0.746). CONCLUSION: Our assessment suggested there was no significant association between the MTHFD1 polymorphism rs 2236225 (c.1958G>A) and the susceptibility to NSCL/P. Further investigations using a large sample size and a more advanced technique should be adopted to reach a more precise conclusion in the future. PMID- 26834982 TI - Discovering, Indexing and Interlinking Information Resources. AB - The social media revolution is having a dramatic effect on the world of scientific publication. Scientists now publish their research interests, theories and outcomes across numerous channels, including personal blogs and other thematic web spaces where ideas, activities and partial results are discussed. Accordingly, information systems that facilitate access to scientific literature must learn to cope with this valuable and varied data, evolving to make this research easily discoverable and available to end users. In this paper we describe the incremental process of discovering web resources in the domain of agricultural science and technology. Making use of Linked Open Data methodologies, we interlink a wide array of custom-crawled resources with the AGRIS bibliographic database in order to enrich the user experience of the AGRIS website. We also discuss the SemaGrow Stack, a query federation and data integration infrastructure used to estimate the semantic distance between crawled web resources and AGRIS. PMID- 26834983 TI - Effect of sex in the MRMT-1 model of cancer-induced bone pain. AB - An overwhelming amount of evidence demonstrates sex-induced variation in pain processing, and has thus increased the focus on sex as an essential parameter for optimization of in vivo models in pain research. Mammary cancer cells are often used to model metastatic bone pain in vivo, and are commonly used in both males and females. Here we demonstrate that compared to male rats, female rats have an increased capacity for recovery following inoculation of MRMT-1 mammary cells, thus potentially causing a sex-dependent bias in interpretation of the data. PMID- 26834983 TI - Effect of sex in the MRMT-1 model of cancer-induced bone pain. AB - An overwhelming amount of evidence demonstrates sex-induced variation in pain processing, and has thus increased the focus on sex as an essential parameter for optimization of in vivo models in pain research. Mammary cancer cells are often used to model metastatic bone pain in vivo, and are commonly used in both males and females. Here we demonstrate that compared to male rats, female rats have an increased capacity for recovery following inoculation of MRMT-1 mammary cells, thus potentially causing a sex-dependent bias in interpretation of the data. PMID- 26834985 TI - iCTNet2: integrating heterogeneous biological interactions to understand complex traits. AB - iCTNet (integrated Complex Traits Networks) version 2 is a Cytoscape app and database that allows researchers to build heterogeneous networks by integrating a variety of biological interactions, thus offering a systems-level view of human complex traits. iCTNet2 is built from a variety of large-scale biological datasets, collected from public repositories to facilitate the building, visualization and analysis of heterogeneous biological networks in a comprehensive fashion via the Cytoscape platform. iCTNet2 is freely available at the Cytoscape app store. PMID- 26834989 TI - Twittering About Research: A Case Study of the World's First Twitter Poster Competition. AB - The Royal Society of Chemistry held, to our knowledge, the world's first Twitter conference at 9am on February 5 (th), 2015. The conference was a Twitter-only conference, allowing researchers to upload academic posters as tweets, replacing a physical meeting. This paper reports the details of the event and discusses the outcomes, such as the potential for the use of social media to enhance scientific communication at conferences. In particular, the present work argues that social media outlets such as Twitter broaden audiences, speed up communication, and force clearer and more concise descriptions of a researcher's work. The benefits of poster presentations are also discussed in terms of potential knowledge exchange and networking. This paper serves as a proof-of-concept approach for improving both the public opinion of the poster, and the enhancement of the poster through an innovative online format that some may feel more comfortable with, compared to face-to-face communication. PMID- 26834990 TI - The Antibody Two-Step Solution. AB - Problems with antibody quality have been described in numerous recent publications. In the present commentary it is argued that these quality problems are due primarily to issues of antibody variability and antibody validation. Further it is argued that the problem of antibody variability must be solved before validation can be useful. A two-step solution to the antibody problem is thus proposed. PMID- 26834995 TI - Quality of histone modification antibodies undermines chromatin biology research. AB - Histone post-translational modification (PTM) antibodies are essential research reagents in chromatin biology. However, they suffer from variable properties and insufficient documentation of quality. Antibody manufacturers and vendors should provide detailed lot-specific documentation of quality, rendering further quality checks by end-customers unnecessary. A shift from polyclonal antibodies towards sustainable reagents like monoclonal or recombinant antibodies or histone binding domains would help to improve the reproducibility of experimental work in this field. PMID- 26834994 TI - Machine learning models identify molecules active against the Ebola virus in vitro. AB - The search for small molecule inhibitors of Ebola virus (EBOV) has led to several high throughput screens over the past 3 years. These have identified a range of FDA-approved active pharmaceutical ingredients (APIs) with anti-EBOV activity in vitro and several of which are also active in a mouse infection model. There are millions of additional commercially-available molecules that could be screened for potential activities as anti-EBOV compounds. One way to prioritize compounds for testing is to generate computational models based on the high throughput screening data and then virtually screen compound libraries. In the current study, we have generated Bayesian machine learning models with viral pseudotype entry assay and the EBOV replication assay data. We have validated the models internally and externally. We have also used these models to computationally score the MicroSource library of drugs to select those likely to be potential inhibitors. Three of the highest scoring molecules that were not in the model training sets, quinacrine, pyronaridine and tilorone, were tested in vitro and had EC 50 values of 350, 420 and 230 nM, respectively. Pyronaridine is a component of a combination therapy for malaria that was recently approved by the European Medicines Agency, which may make it more readily accessible for clinical testing. Like other known antimalarial drugs active against EBOV, it shares the 4 aminoquinoline scaffold. Tilorone, is an investigational antiviral agent that has shown a broad array of biological activities including cell growth inhibition in cancer cells, antifibrotic properties, alpha7 nicotinic receptor agonist activity, radioprotective activity and activation of hypoxia inducible factor-1. Quinacrine is an antimalarial but also has use as an anthelmintic. Our results suggest data sets with less than 1,000 molecules can produce validated machine learning models that can in turn be utilized to identify novel EBOV inhibitors in vitro. PMID- 26843956 TI - alpha-synuclein-lanthanide metal ions interaction: binding sites, conformation and fibrillation. AB - BACKGROUND: The pathological hallmark of Parkinson's disease is the deposition of cytoplasmic neuronal inclusions termed Lewy bodies. The major component of Lewy bodies is amyloid fibrils of alpha-synuclein. To investigate what causes alpha synuclein aggregation is essential to understand its pathological roles in Parkinson's disease. Various metal ions, including iron and copper, have been implicated in the pathogenesis of Parkinson's disease. Divalent metal ions can regulate alpha-synuclein fibrillation rate, however, few studies have been performed to investigate how trivalent metal ions interact with alpha-synuclein and their effect on alpha-synuclein fibrillation. The study of the interaction between divalent and trivalent metal ions with alpha-synuclein is of vital importance to realize the mechanism of alpha-synuclein fibrillation. RESULTS: Here we used nuclear magnetic resonance spectroscopy to determine the trivalent metal ions (lanthanides) binding sites in alpha-synuclein. We found that lanthanide metal ions not only bind non-specifically to the C-terminal domain of alpha-synuclein, but also transiently interact with residues contain carboxyl groups in the N-terminal and NAC regions, the latter binding sites were not found for divalent cations. In addition, lanthanide ions bound alpha-synuclein exhibits slower conformational exchange rate. Compare to divalent cations, lanthanide ions accelerate alpha-synuclein fibrillation much faster. CONCLUSIONS: We identified the lanthanide metal ions binding sites in alpha-synuclein and found a hierarchal effect for lanthanide ions binding to alpha-synuclein, driven by the interaction with aspartic acids and glutamic acids residues. Lanthanide ions binding also induced conformational dynamics change of alpha-synuclein. Compared to divalent cations, lanthanide metal ions significantly accelerated alpha-synuclein fibrillation, possibly due to the different inherent properties such as charge, binding sites and coordination modes. PMID- 26843960 TI - Estradiol: micrograms or milligrams. AB - Estrogen is used to induce puberty in peripubertal girls with hypogonadism. Although both synthetic and natural forms are available, along with different routes of administration, in the UK oral ethinyl estradiol and the low-dose oral contraceptive pill are commonly used as hormone replacement therapy for practical reasons. We present five peripubertal girls (aged 12.5-14.9 years) with hypogonadism (two with primary hypogonadism due to Turner syndrome and three with central (secondary) hypogonadism as part of multiple pituitary hormone deficiency) who for a variety of reasons have received milligram doses of estradiol (E2) in error for between 6 weeks and 6 months, instead of the expected microgram doses of ethinyl estradiol. Although there are no direct comparisons in peripubertal girls between synthetic and natural estrogens, all girls had vaginal bleeding whilst receiving the milligram doses and have ended up with reduced final heights, below the 9th centile in 1 and below the 2nd centile in 4. Whilst reduction in final height may be part of the underlying condition (especially in Turner syndrome) the two girls with height predictions performed prior to receiving the estrogen overdose have not achieved their predicted height. Estrogen is one of the few drugs which is available in both milligram and microgram formulations. Clinicians need to be alert to the possibility of patients receiving the wrong formulation and dosage in error. LEARNING POINTS: Girls with primary and secondary gonadal failure require assistance with pubertal induction.Although several different formulations and route of administration are available, for practical reasons, the majority of girls in the UK receive oral ethinyl estradiol.Estrogen preparations are available in both milligram and microgram formulations, with potential for receiving the wrong dose.Girls receiving milligram rather than microgram preparations all had vaginal bleeding and a short final height. PMID- 26843957 TI - Genotype-phenotype correlations of amyotrophic lateral sclerosis. AB - Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by progressive neuronal loss and degeneration of upper motor neuron (UMN) and lower motor neuron (LMN). The clinical presentations of ALS are heterogeneous and there is no single test or procedure to establish the diagnosis of ALS. Most cases are diagnosed based on symptoms, physical signs, progression, EMG, and tests to exclude the overlapping conditions. Familial ALS represents about 5 ~ 10 % of ALS cases, whereas the vast majority of patients are sporadic. To date, more than 20 causative genes have been identified in hereditary ALS. Detecting the pathogenic mutations or risk variants for each ALS individual is challenging. However, ALS patients carrying some specific mutations or variant may exhibit subtly distinct clinical features. Unraveling the respective genotype phenotype correlation has important implications for the genetic explanations. In this review, we will delineate the clinical features of ALS, outline the major ALS-related genes, and summarize the possible genotype-phenotype correlations of ALS. PMID- 26843958 TI - Common ground in Attention Deficit Hyperactivity Disorder (ADHD) and Borderline Personality Disorder (BPD)-review of recent findings. AB - Considerable overlap in diagnostic criteria and shared psychopathologic symptoms in attention deficit hyperactivity disorder (ADHD) and borderline personality disorder (BPD) have stimulated research activities in this field. Longitudinal studies have shown that BPD is frequently diagnosed in adult patients who had been diagnosed with ADHD in childhood. The question of whether ADHD and BPD randomly co-occur as comorbidities, have similar origins or share common pathological mechanisms remains unresolved. Some authors suggest that ADHD contributes to the development of BPD via various mechanisms, and therefore consider it a risk factor for later BPD development. In this article the evidence for the co-occurrence of these disorders will be reviewed as well as studies on their common genetic and environmental influences. Temperamental and developmental issues will be reviewed, and shared features such as impulsivity and emotion dysregulation discussed. From a therapeutic perspective, few studies have investigated psychotherapeutic treatment of the comorbid condition, though the issue is highly important to the management of patients suffering from both disorders. Some thought is given to how therapeutic methods and approaches can be modified to benefit patients, and to their possible succession. PMID- 26843961 TI - Somatic RET mutation in a patient with pigmented adrenal pheochromocytoma. AB - Pheochromocytomas (PCC) and paraganglioma (PGL) are rare neuroendocrine tumors arising from chromaffin cells of the neural crest. Mutations in the RET-proto oncogene are associated with sporadic pheochromocytoma, familial or sporadic medullary thyroid carcinoma (MTC) and multiple endocrine neoplasia type 2. In the past, only few cases of pigmented PCCs, PGLs, and one case of pigmented MTC have been reported in the literature. Herein, we present the case of a 77-year old woman with a history of Tako-tsubo-cardiomyopathy and laboratory, as well as radiological, high suspicion of pheochromocytoma, who underwent left-sided adrenalectomy. The 3 cm tumor, which was located on the upper pole of the left adrenal, appeared highly pigmented with dark red to black color. Histologic examinations revealed highly pleomorphic cells with bizarre, huge hyperchromatic nuclei, that immunohistochemically were positive for chromogranin A and synaptophysin, focally positive for HMB45 and negative for melan A. These clinical and pathological features led to the diagnosis of the rare variant of a melanotic 'black' pheochromocytoma. In our case a somatic RET mutation in exon 16 (RET c.2753T>C, p.Met918Thy) was detected by targeted next generation sequencing. In summary, this case represents a rare variant of catecholamine-producing tumor with distinct histological features. A potential relationship between the phenotype, the cellular origin and the genetic alterations is discussed. LEARNING POINTS: Pheochromocytoma is a rare neuroendocrine tumor.Pigmentation is seen in several types of tumors arising from the neural crest. The macroscopic black aspect can mislead to the diagnosis of a metastasis deriving from a malignant melanoma.RET mutation are seen in catecholamine and non-catecholamine producing tumors of the same cellular origin. PMID- 26843963 TI - An economic analysis of varicella immunization in the Singapore military. AB - BACKGROUND: Varicella outbreaks occur frequently in closed environments such as those of militaries. This paper compares the economic outcomes of varicella vaccination in enlisted servicemen without prior reported varicella infection or vaccination. METHODS: We analyzed the economic outcomes of a varicella vaccination program on all enlisted servicemen without prior reported varicella infection or vaccination in the Singapore Armed Forces (SAF) between December 11, 2010 - December 20, 2013, compared with the previous program of varicella vaccination only for selected personnel between December 1, 2007 - December 10, 2010. RESULTS: In the at-risk population of all active SAF servicemen, the program of varicella vaccination for all servicemen without prior reported varicella infection or vaccination upon enlistment would save 72.0 work days per 1000 (95 % CI: 61.2 - 82.9), valued at SG$6,544 per 1000 (95 % CI: 6,524 - 6,564), i.e., costing SG$91.5 per work day saved (95 % CI: 78.7 - 107.3). This also results in a reduction of 2.7 varicella cases per 1000 and 5.43 outbreaks per 10000, or a total savings of SG$1,695 per 1000 (95 % CI: -2,730 - 6,834), taking into account the cost of work days lost over a three-year period, compared with the previous regime of vaccinations only for selected individuals. CONCLUSION: The varicella vaccination strategy targeting all enlisted servicemen without prior reported varicella infection or vaccination is able to prevent varicella infections and outbreaks, thus reducing absenteeism and days lost. PMID- 26843962 TI - Design of and rationale for the Japan Diabetes Optimal Integrated Treatment study for 3 major risk factors of cardiovascular diseases (J-DOIT3): a multicenter, open-label, randomized, parallel-group trial. AB - OBJECTIVE: Multifactorial intervention including the management of levels of blood glucose (BG), blood pressure (BP), and lipids has been suggested to decrease cardiovascular disease (CVD) risk. However, the target ideal and feasible levels for these individual parameters have not been fully evaluated. In this study, we examine the hypothesis that stricter control compared with the current targets in the Japanese guideline for BG, BP, and lipids could efficiently and safely reduce CVD risk. RESEARCH DESIGN AND METHODS: We screened patients with type 2 diabetes and hypertension and/or dyslipidemia among 81 hospitals in Japan and allocated them into 2 groups: the intensive therapy group (ITG) and the conventional therapy group (CTG). For the 2 respective groups, the target for glycated hemoglobin (HbA1c) is <6.2% (44 mmol/mol) and <6.9% (52 mmol/mol), for BP it is <120/75 mm Hg and <130/80 mm Hg, and for low-density lipoprotein cholesterol it is <80 mg/dL (<70 mg/dL in the presence of CVD history) and <120 mg/dL (<100 mg/dL in the presence of CVD history). The primary end point is the occurrence of CVD events or death by any cause. These patients are scheduled for stepwise intensifications of medication for BG, BP, and lipid control in the ITG, until the number of primary end point events reaches 250. RESULTS: We recruited 2542 patients and randomly allocated 1271 into the ITG and 1271 into the CTG between June 2006 and March 2009. The mean HbA1c was 8.0% (64 mmol/mol) and the mean duration of diabetes was 8.3 years. CONCLUSIONS: This randomized controlled study will test the hypothesis that strict multifactorial intervention therapy is effective for the prevention of CVDs in patients with type 2 diabetes who are at high CVD risk. TRIAL REGISTRATION NUMBER: NCT00300976. PMID- 26843964 TI - Developments in Diagnosis of Visceral Leishmaniasis in the Elimination Era. AB - Visceral leishmaniasis (VL) is the most devastating parasitic infection worldwide causing high morbidity and mortality. Clinical presentation of VL ranges from asymptomatic or subclinical infection to severe and complicated symptomatic disease. A major challenge in the clinical management of VL is the weakness of health systems in disease endemic regions. People affected by VL mostly present to primary health care centers (PHCs), often late in their therapeutic itinerary. PHC physicians face a major challenge: they do not deal with a single disease issue but with patients presenting with complaints pointing to several diagnostic possibilities. Risk exists when some patients having less clinical manifestations are misdiagnosed. Therefore, field based accurate, sensitive, and cost effective rapid diagnostic tools that can detect disease in its mildest form are essential for effective control and reaching the goal of VL elimination. In this review, we discuss the current status and challenges of various diagnostic tools for the diagnosis of VL and assess their application in resource poor settings. PMID- 26843967 TI - Ion transport properties of magnesium bromide/dimethyl sulfoxide non-aqueous liquid electrolyte. AB - Nonaqueous liquid electrolyte system based dimethyl sulfoxide DMSO and magnesium bromide (MgBr2) is synthesized via 'Solvent-in-Salt' method for the application in magnesium battery. Optimized composition of MgBr2/DMSO electrolyte exhibits high ionic conductivity of 10(-2) S/cm at ambient temperature. This study discusses different concentrations from 0 to 5.4 M of magnesium salt, representing low, intermediate and high concentrations of magnesium salt which are examined in frequency dependence conductivity studies. The temperature dependent conductivity measurements have also been carried out to compute activation energy (Ea ) by least square linear fitting of Arrhenius plot: 'log sigma - 1/T. The transport number of Mg(2+) ion determined by means of a combination of d.c. and a.c. techniques is ~0.7. A prototype cell was constructed using nonaqueous liquid electrolyte with Mg anode and graphite cathode. The Mg/graphite cell shows promising cycling. PMID- 26843965 TI - Identification of rheumatoid arthritis biomarkers based on single nucleotide polymorphisms and haplotype blocks: A systematic review and meta-analysis. AB - Genetics of autoimmune diseases represent a growing domain with surpassing biomarker results with rapid progress. The exact cause of Rheumatoid Arthritis (RA) is unknown, but it is thought to have both a genetic and an environmental bases. Genetic biomarkers are capable of changing the supervision of RA by allowing not only the detection of susceptible individuals, but also early diagnosis, evaluation of disease severity, selection of therapy, and monitoring of response to therapy. This review is concerned with not only the genetic biomarkers of RA but also the methods of identifying them. Many of the identified genetic biomarkers of RA were identified in populations of European and Asian ancestries. The study of additional human populations may yield novel results. Most of the researchers in the field of identifying RA biomarkers use single nucleotide polymorphism (SNP) approaches to express the significance of their results. Although, haplotype block methods are expected to play a complementary role in the future of that field. PMID- 26843966 TI - A review on plants extract mediated synthesis of silver nanoparticles for antimicrobial applications: A green expertise. AB - Metallic nanoparticles are being utilized in every phase of science along with engineering including medical fields and are still charming the scientists to explore new dimensions for their respective worth which is generally attributed to their corresponding small sizes. The up-and-coming researches have proven their antimicrobial significance. Among several noble metal nanoparticles, silver nanoparticles have attained a special focus. Conventionally silver nanoparticles are synthesized by chemical method using chemicals as reducing agents which later on become accountable for various biological risks due to their general toxicity; engendering the serious concern to develop environment friendly processes. Thus, to solve the objective; biological approaches are coming up to fill the void; for instance green syntheses using biological molecules derived from plant sources in the form of extracts exhibiting superiority over chemical and/or biological methods. These plant based biological molecules undergo highly controlled assembly for making them suitable for the metal nanoparticle syntheses. The present review explores the huge plant diversity to be utilized towards rapid and single step protocol preparatory method with green principles over the conventional ones and describes the antimicrobial activities of silver nanoparticles. PMID- 26843968 TI - The Egyptian clinical trials' registry profile: Analysis of three trial registries (International Clinical Trials Registry Platform, Pan-African Clinical Trials Registry and clinicaltrials.gov). AB - Registering clinical trials (CTs) in public domains enhances transparency, increases trust in research, improves participation and safeguards against publication bias. This work was done to study the profile of clinical research in Egypt in three CT registries with different scopes: the WHO International CT Registry Platform (ICTRP), the continental Pan-African CT Registry (PACTR) and the US clinicaltrials.gov (CTGR). In March 2014, ICTRP, PACTR and CTGR were searched for clinical studies conducted in Egypt. It was found that the number of studies conducted in Egypt (percentage) was 686 (0.30%) in ICTRP, 56 (11.3%) in PACTR and 548 (0.34%) in CTGR. Most studies were performed in universities and sponsored by university/organization, industry or individual researchers. Inclusion of adults from both genders predominated. The median number of participants per study in the three registries ranged between 63 and 155. The conditions researched differed among the three registries and study purpose was mostly treatment followed by prevention. Endpoints were mostly efficacy followed by safety. Observational:Interventional studies (i.e. clinical trials) represented 15.5%:84.5% in ICTRP, 0%:100% in PACTR and 16.4%:83.6% in CTGR. Most interventions were drugs or procedures. Observational studies were mostly prospective and cohort studies. Most CTs were phase 3 and tested drugs or procedures. Parallel group assignment and random allocation predominated. Blinding was implemented in many of trials and was mostly double-blind. We conclude that CTs from Egypt in trial registries are apparently low and do not accurately reflect clinical research conducted in Egypt or its potential. Development of an Egyptian CT registry is eagerly needed. Registering all Egyptian CTs in public domains is highly recommended. PMID- 26843969 TI - Effect of leaching with 5-6 N H2SO4 on thermal kinetics of rice husk during pure silica recovery. AB - Rice husk is a potential source for renewable energy and silica. To extract the maximum amount of silica, usually the rice husk is treated with strong acids that burn the organic part leaving behind a black residue. In this research, sulfuric acid is used as an oxidizing agent. Efforts are focused to find out more about the behavior of acid-treated rice husk by using thermal exposure, and results are compared with results for raw rice husk which is thermally exposed but not acid treated. Reaction ratio of rice husk combustion and energy of activation were calculated using the thermogravimetric data. Acid treatment was found influential in initiating degradation earlier compared to raw husk and an overall increase in value of activation energy was observed when heating rate was increased. PMID- 26843970 TI - Selective determination of dimenhydrinate in presence of six of its related substances and potential impurities using a direct GC/MS method. AB - A novel simple, direct and selective gas chromatography-mass spectrometry (GC/MS) procedure was developed for the determination of the antihistamine drug dimenhydrinate (DMH) in presence of six of its related substances and potential impurities, namely, diphenylmethane, diphenylmethanol, benzophenone, orphenadrine, caffeine and 8-chlorocaffeine. The method involved resolution of the underivatized compounds using a trifluoropropylmethyl polysiloxane (Rtx-200) capillary column and the mass spectrometric detection was carried out in the electron-impact (EI) mode. Excellent baseline separation of DMH and the cited related substances was achieved in less than 15 min. Quantification of the parent drug DMH was based on measuring its peak area. The reliability and analytical performance of the proposed method were validated with respect to linearity, range, precision, accuracy, specificity, robustness, detection and quantification limits. Calibration curve of DMH was linear over the range 50-500 MUg/mL with determination coefficient (R (2)) = 0.9982. The proposed method was successfully applied for the assay of DMH in tablets dosage form with recoveries >96.80%. PMID- 26843971 TI - On non-negative estimation of variance components in mixed linear models. AB - Alternative estimators have been derived for estimating the variance components according to Iterative Almost Unbiased Estimation (IAUE). As a result two modified IAUEs are introduced. The relative performances of the proposed estimators and other estimators are studied by simulating their bias, Mean Square Error and the probability of getting negative estimates under unbalanced nested factorial model with two fixed crossed factorial and one nested random factor. Finally the Empirical Quantile Dispersion Graph (EQDG), which provides a comprehensive picture of the quality of estimation, is depicted corresponding to all the studied methods. PMID- 26843972 TI - N-succinyl chitosan-dialdehyde starch hybrid hydrogels for biomedical applications. AB - A new class of injectable, biocompatible and biodegradable hydrogel is reported. This hydrogel is derived from N-succinyl chitosan (SCS) mixed with water-soluble dialdehyde starch (DAS) without using a conventional chemical crosslinker. The hybrid hydrogel is formed owing to the Schiff's base reaction between amine groups of SCS and dialdehyde groups of DAS to form -CH 000000000000 000000000000 000000000000 111111111111 000000000000 111111111111 000000000000 000000000000 000000000000 N- group. SCS, DAS, and SCS-DAS hybrid hydrogels were synthesized and then characterized by FTIR analysis spectroscopy. The influence of SCS:DAS ratio in hybrid polymers solution on physicochemical properties of resultant hydrogels (e.g. gelation time, gel fraction (%) and equilibrium swelling ratio), surface morphology, in vitro weight loss (%), and mechanical stability was examined. The results demonstrated that SCS content has a profound role for forming tighter crosslinked hybrid hydrogels, where the increase of SCS content reduces the time for hydrogel forming. Also, the water uptake and hydrolytic weight loss decrease. Meanwhile, the DAS content increases, and mechanical properties of SCS-DAS hybrid hydrogels decrease. Curcumin release profile and adhered HGF cells on hydrogel surface sharply influenced the SCS portion in hybrid hydrogel composition. The SCS-DAS hybrid hydrogel properties afforded a possible opportunity to be used as a covalent in situ forming hybrid hydrogels in biomedical applications such as, tissue engineering and cartilage repair. PMID- 26843973 TI - Kinetics studies of uranium sorption by powdered corn cob in batch and fixed bed system. AB - Sorption of uranium (VI) from aqueous solution onto powdered corn cob has been carried out using batch and fixed-bed technique. The experimental results in batch technique were fitted well with pseudo second-order kinetics model. In the fixed bed technique, Thomas and Bohart-Adams models were evaluated by linear regression analysis for U(VI) uptake in different flow rates, bed heights and initial concentrations. The column experimental data were fitted well with Thomas mode (r (2) = 0.999), but the Bohart-Adams model (r (2) = 0.911), predicted poor performance of fixed-bed column. PMID- 26843974 TI - Accurate dynamic power estimation for CMOS combinational logic circuits with real gate delay model. AB - Dynamic power estimation is essential in designing VLSI circuits where many parameters are involved but the only circuit parameter that is related to the circuit operation is the nodes' toggle rate. This paper discusses a deterministic and fast method to estimate the dynamic power consumption for CMOS combinational logic circuits using gate-level descriptions based on the Logic Pictures concept to obtain the circuit nodes' toggle rate. The delay model for the logic gates is the real-delay model. To validate the results, the method is applied to several circuits and compared against exhaustive, as well as Monte Carlo, simulations. The proposed technique was shown to save up to 96% processing time compared to exhaustive simulation. PMID- 26843975 TI - Power conditioning using dynamic voltage restorers under different voltage sag types. AB - Voltage sags can be symmetrical or unsymmetrical depending on the causes of the sag. At the present time, one of the most common procedures for mitigating voltage sags is by the use of dynamic voltage restorers (DVRs). By definition, a DVR is a controlled voltage source inserted between the network and a sensitive load through a booster transformer injecting voltage into the network in order to correct any disturbance affecting a sensitive load voltage. In this paper, modelling of DVR for voltage correction using MatLab software is presented. The performance of the device under different voltage sag types is described, where the voltage sag types are introduced using the different types of short-circuit faults included in the environment of the MatLab/Simulink package. The robustness of the proposed device is evaluated using the common voltage sag indices, while taking into account voltage and current unbalance percentages, where maintaining the total harmonic distortion percentage of the load voltage within a specified range is desired. Finally, several simulation results are shown in order to highlight that the DVR is capable of effective correction of the voltage sag while minimizing the grid voltage unbalance and distortion, regardless of the fault type. PMID- 26843976 TI - Assessment of antibody level and avidity against Bordetella pertussis in a cohort of Egyptian individuals aged 1-18 years. AB - Pertussis specific antibodies were studied with respect to quality and quantity in a cohort of apparently healthy Egyptian children and adolescents, with their age range between 1 and 18 years, in an attempt to get a close and clear insight into the current humoral immunization status in this specified group and to try find a relation between the antibody levels and their avidities in eradication of this devastating infectious disease. Our results showed that avidity increase was most marked in young school children (6-8 years) where it seemed to reach a plateau in older children and adolescents. Antibody titer was highest in toddlers (1-2 years) and young school children (6-8 years) groups, most probably following vaccination and/or booster doses. Among children aged 1-5 years, 28% had highly avid and 50% had high titer antibodies, whereas in adolescents aged 13-18 years, 70% had highly avid antibodies and only 30% had high titer antibodies. The results clearly demonstrated that while levels of anti-Bordetella pertussis (B. pertussis) antibodies wane with growing age, the avidity seems to increase, to a plateau, irrespective of further antigen exposure in a pattern showing complete independence of avidity on concentration. The present study draws attention to the importance of avidity measurements, together with conventional ELISAs, for evaluating immunity against pertussis. Being based on a limited sample size, it could open doors for larger-scale surveys to be possible indicators for the need and timing of booster vaccination doses among Egyptians. PMID- 26843977 TI - Adsorption of Methylene Blue, Bromophenol Blue, and Coomassie Brilliant Blue by alpha-chitin nanoparticles. AB - Expelling of dyestuff into water resource system causes major thread to the environment. Adsorption is the cost effective and potential method to remove the dyes from the effluents. Therefore, an attempt was made to study the adsorption of dyestuff (Methylene Blue (MB), Bromophenol Blue (BPB) and Coomassie Brilliant Blue (CBB)) by alpha-chitin nanoparticles (CNP) prepared from Penaeus monodon (Fabricius, 1798) shell waste. On contrary to the most recognizable adsorption studies using chitin, this is the first study using unique nanoparticles of ?50 nm used for the dye adsorption process. The results showed that the adsorption process increased with increase in the concentration of CNP, contact time and temperature with the dyestuff, whereas the adsorption process decreased with increase in the initial dye concentration and strong acidic pH. The results from Fourier transform infrared (FTIR) spectroscopy confirmed that the interaction between dyestuff and CNP involved physical adsorption. The adsorption process obeys Langmuir isotherm (R (2) values were 0.992, 0.999 and 0.992 for MB, BPB and CBB, and RL value lies between 0 and 1 for all the three dyes) and pseudo second order kinetics (R (2) values were 0.996, 0.999 and 0.996 for MB, BPB and CBB) more effectively. The isotherm and kinetic models confirmed that CNP can be used as a suitable adsorbent material for the removal of dyestuff from effluents. PMID- 26843978 TI - A new multiobjective performance criterion used in PID tuning optimization algorithms. AB - In PID controller design, an optimization algorithm is commonly employed to search for the optimal controller parameters. The optimization algorithm is based on a specific performance criterion which is defined by an objective or cost function. To this end, different objective functions have been proposed in the literature to optimize the response of the controlled system. These functions include numerous weighted time and frequency domain variables. However, for an optimum desired response it is difficult to select the appropriate objective function or identify the best weight values required to optimize the PID controller design. This paper presents a new time domain performance criterion based on the multiobjective Pareto front solutions. The proposed objective function is tested in the PID controller design for an automatic voltage regulator system (AVR) application using particle swarm optimization algorithm. Simulation results show that the proposed performance criterion can highly improve the PID tuning optimization in comparison with traditional objective functions. PMID- 26843979 TI - Structural, electrical conductivity and dielectric behavior of Na2SO4-LDT composite solid electrolyte. AB - A series of composite materials of general molecular formula (1 - x) Na2SO4 - (x) LDT was prepared by solid state reaction method. The phase structure and functionalization of these materials were defined by X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) respectively. Differential thermal analysis (DTA) revealed that the hump of phase transition at 250 degrees C has decreased while its thermal stability was enhanced. Scanning electron microscopy signifies the presence of improved rigid surfaces and interphases that are accountable for the high ionic conduction due to dispersion of LDT particles in the composite systems. Arrhenius plots of the conductance show the maximum conductivity, sigma = 4.56 * 10(-4) S cm(-1) at 500 degrees C for the x = 0.4 composition with the lowest activation energy 0.34 eV in the temperature range of 573-773 K. The value of dielectric constant was decreased with increasing frequency and follows the usual trend. PMID- 26843982 TI - On the boundedness and integration of non-oscillatory solutions of certain linear differential equations of second order. AB - In this paper, certain system of linear homogeneous differential equations of second-order is considered. By using integral inequalities, some new criteria for bounded and [Formula: see text]-solutions, upper bounds for values of improper integrals of the solutions and their derivatives are established to the considered system. The obtained results in this paper are considered as extension to the results obtained by Kroopnick (2014) [1]. An example is given to illustrate the obtained results. PMID- 26843980 TI - Efficiency of calcium phosphate composite nanoparticles in targeting Ehrlich carcinoma cells transplanted in mice. AB - The present study aimed to investigate the mode of action of nano-CaPs in vivo as a therapy for solid tumor in mice. To achieve this goal, Ehrlich Ascites Carcinoma (EAC) was transplanted into 85 Swiss male albino mice. After nine days, the mice were divided into 9 groups. Groups 1 and 2 were allocated as the EAC control. Groups 3 and 4 were injected once intratumorally (IT) by nano-calcium phosphate (nano-CaP). Groups 5 and 6 received once intraperitoneal injection (IP) of nano-CaP. Groups 7, 8, and 9 received nano-CaP (IP) weekly. Blood samples and thigh skeletal muscle were collected after three weeks from groups 1, 3, 5, and 7 and after four weeks from groups 2, 4, 6, and 8. On the other hand, group 9 received nano-CaP (IP) for four weeks and lasted for three months to follow up the recurrence of tumor and to ensure the safety of muscle by histopathological analysis. Tumor growth was monitored twice a week throughout the experiment. DNA fragmentation of tumor cells was evaluated. In thigh tissue, noradrenaline, dopamine, serotonin (5HT), and gamma-aminobutyric acid (GABA) were measured. In serum, 8-Hydroxy-deoxyguanosine (8-OHDG), adenosine triphosphate (ATP), and vascular endothelial growth factor (VEGF) were analyzed. Histopathological and biochemical results showed a significant therapeutic effect of nano-CaP on implanted solid tumor and this effect was more pronounced in the animals treated IP for four weeks. This improvement was evident from the repair of fragmented DNA, the significant decrease of caspase-3, 8-OHDG, myosin, and VEGF, and the significant increase of neurotransmitters (NA, DA, 5HT, and GABA). Additionally, histopathological examination showed complete recovery of cancer cells in the thigh muscle after three months. PMID- 26843981 TI - Phenotypic and genotypic characterization of peptidoglycan hydrolases of Lactobacillus sakei. AB - Lactobacillus sakei, a lactic acid bacterium naturally found in fresh meat and sea products, is considered to be one of the most important bacterial species involved in meat fermentation and bio-preservation. Several enzymes of Lb. sakei species contributing to microbial safeguarding and organoleptic properties of fermented-meat were studied. However, the specific autolytic mechanisms and associated enzymes involved in Lb. sakei are not well understood. The autolytic phenotype of 22 Lb. sakei strains isolated from Tunisian meat and seafood products was evaluated under starvation conditions, at pH 6.5 and 8.5, and in the presence of different carbon sources. A higher autolytic rate was observed when cells were grown in the presence of glucose and incubated at pH 6.5. Almost all strains showed high resistance to mutanolysin, indicating a minor role of muramidases in Lb. sakei cell lysis. Using Micrococcus lysodeikticus cells as a substrate in activity gels zymogram, peptidoglycan hydrolase (PGH) patterns for all strains was characterized by two lytic bands of ~80 (B1) and ~70 kDa (B2), except for strain BMG.167 which harbored two activity signals at a lower MW. Lytic activity was retained in high salt and in acid/basic conditions and was active toward cells of Lb. sakei, Listeria monocytogenes, Listeria ivanovii and Listeria innocua. Analysis of five putative PGH genes found in the Lb. sakei 23 K model strain genome, indicated that one gene, lsa1437, could encode a PGH (N acetylmuramoyl-L-alanine amidase) containing B1 and B2 as isoforms. According to this hypothesis, strain BMG.167 showed an allelic version of lsa1437 gene deleted of one of the five LysM domains, leading to a reduction in the MW of lytic bands and the high autolytic rate of this strain. Characterization of autolytic phenotype of Lb. sakei should expand the knowledge of their role in fermentation processes where they represent the dominant species. PMID- 26843983 TI - The Cost-Effectiveness of Continuous Erythropoiesis Receptor Activator Once Monthly versus Epoetin Thrice Weekly for Anaemia Management in Chronic Haemodialysis Patients. AB - Introduction. The aim of this study was to compare the cost-effectiveness of continuous erythropoietin receptor activator (CERA) once monthly to epoetin beta (EpoB) thrice weekly to maintain haemoglobin (Hb) within the range 10.5-12 g/dL. Methods. Prospective cohort study and cost-effectiveness analysis. Chronic haemodialysis patients (CHP), being treated with EpoB, were selected for two periods of follow-up: period 1, maintaining prior treatment with EpoB, and period 2, conversion to CERA once monthly. Hb concentrations and costs were measured monthly. Health care payer perspective for one year was adopted. Results. 75 CHP completed the study, with a mean age of 52.9 +/- 14.3 years. Baseline Hb was 11.14 +/- 1.18 g/dL in EpoB phase and 11.46 +/- 0.79 g/dL in CERA phase; we observed a significant increase in the proportion of patients successfully treated (Hb within the recommended range), 65.3% versus 70.7%, p: 0.008, and in the average effectiveness by 4% (0.55 versus 0.59). Average cost-effectiveness ratios were 6013.86 and 5173.64$, with an ICER CERA to EpoB at -6457.5$. Conclusion. Our health economic evaluation of ESA use in haemodialysis patients suggests that the use of CERA is cost-effective compared with EpoB. PMID- 26843984 TI - Transcriptional Activation of p53 during Cold Induced Torpor in the 13-Lined Ground Squirrel Ictidomys tridecemlineatus. AB - The transcription factor p53 is located at the centre of multiple pathways relating the cellular response to stress. Commonly known as a tumor suppressor, it is responsible for initiating diverse actions to protect the integrity of the genome, ranging from cell cycle arrest to apoptosis. This study investigated the regulation of p53 protein in hibernating 13-lined ground squirrel Ictidomys tridecemlineatus during multiple stages of the torpor-arousal cycle. Transcript and protein levels of p53 were both elevated in the skeletal muscle during early and late torpor stages of the hibernation cycle. Nuclear localization of p53 was also increased during late torpor, and this is associated with an increase in its DNA binding activity and expression of p53 transcriptional targets p21CIP, gadd45alpha, and 14-3-3sigma. The increase in p53 transcriptional activity appears to be independent of its phosphorylation at Ser-15, Ser-46, and Ser-392, consistent with an absence of checkpoint kinase activation during torpor. Sequence analysis revealed unique amino acid substitutions in the ground squirrel p53 protein, which may contribute to an increase in protein stability compared to nonhibernators. Overall, the study results provided evidences for a potential role of p53 in the protection of the skeletal muscle during torpor. PMID- 26843985 TI - Comparative In Vitro Binding Studies of TiCl2(dpme)2, Ti(ada)2(bzac)2, and TiCl2(bzac)(bpme) Titanium Complexes with Calf-Thymus DNA. AB - The binding of TiCl2(dpme)2 (1), (dpme = 6,6'-dimethyl-2,2'-bipyridine), Ti(ada)2(bzac)2 (2), (ada = adamantylamine; bzac = benzoylacetone), and TiCl2(bzac)(bpme) (3), (bpme = 4,4'-dimethyl-2,2'-bipyrdine) with calf thymus (ct) DNA has been studied by UV-visible spectroscopy, thermal denaturation, and circular dichroism spectroscopy. In UV-visible study complexes 1, 2, and 3 showed red, blue, and red shifts, respectively, upon the addition of ct-DNA along with a significant hyperchromism. The intrinsic binding constants (K b ) calculated from UV-visible absorption studies were 2.3 * 10(3) M(-1), 3.3 * 10(3) M(-1) and, 7.1 * 10(3) M(-1) for complexes 1, 2, and 3, respectively. The change in melting temperature (DeltaT m ) was calculated to be 2-3 degrees C for each complex. Circular dichroism (CD) study showed blue shift for complex 2 and red shift for complexes 1 and 3 along with rise in molecular ellipticity upon the addition of complexes. Results suggest a binding mode of complex 2 different than 1 and 3. PMID- 26843987 TI - Isolation and Antibiotic Susceptibility of the Microorganisms Isolated from Diabetic Foot Infections in Nemazee Hospital, Southern Iran. AB - Background. Diabetic foot infections (DFIs) are a major public health issue and identification of the microorganisms causing such polymicrobial infections is useful to find out appropriate antibiotic therapy. Meanwhile, many reports have shown antibiotic resistance rising dramatically. In the present study, we sought to determine the prevalence of microorganisms detected on culture in complicated DFIs in hospitalized patients and their antibiotic sensitivity profiles. Methods. A cross-sectional study was conducted for a period of 24 months from 2012 to 2014 in Nemazee Hospital, Shiraz, Iran. The demographic and clinical features of the patients were obtained. Antimicrobial susceptibility testing to different agents was carried out using the disc diffusion method. Results. During this period, 122 aerobic microorganisms were isolated from DFIs. Among Gram-positive and Gram negative bacteria, Staphylococcus spp. and E. coli were the most frequent organisms isolated, respectively. Of the isolates, 91% were multidrug while 78% of S. aureus isolates were methicillin resistant. 53% of Gram-negative bacteria were positive for extended-spectrum beta-lactamase. Conclusion. Given the involvement of different microorganisms and emergence of multidrug resistant strains, clinicians are advised to consider culture before initiation of empirical therapy. PMID- 26843986 TI - Stride-Time Variability and Fall Risk in Persons with Multiple Sclerosis. AB - Gait variability is associated with falls in clinical populations. However, gait variability's link to falls in persons with Multiple Sclerosis (PwMS) is not well established. This investigation examined the relationship between stride-time variability, fall risk, and physiological fall risk factors in PwMS. 17 PwMS (62.8 +/- 7.4 years) and 17 age-matched controls (62.8 +/- 5.9 years) performed the 6-minute walk test. Stride-time was assessed with accelerometers attached to the participants' shanks. Stride-time variability was measured by interstride coefficient of variation (CV) of stride-time. The participant's fall risk was measured by the short form physiological profile assessment (PPA). A Spearman correlation analysis was used to determine the relationship between variables. Increased fall risk was strongly associated with increased stride-time CV in both PwMS (rho = 0.71, p < 0.01) and the controls (rho = 0.67, p < 0.01). Fall risk was not correlated with average stride-time (p > 0.05). In PwMS, stride-time CV was related to postural sway (rho = 0.74, p < 0.01) while in the control group, it was related to proprioception (rho = 0.61, p < 0.01) and postural sway (rho = 0.78, p < 0.01). Current observations suggest that gait variability is maybe more sensitive marker of fall risk than average gait parameters in PwMS. It was also noted that postural sway may be potentially targeted to modify gait variability in PwMS. PMID- 26843988 TI - Quality of Life and Volume Reduction in Women with Secondary Lymphoedema Related to Breast Cancer. AB - Purpose. To assess the quality of life (QOL) as a predictor of volume reduction in women undergoing complex physical therapy (CPT) for lymphoedema following breast cancer. Methods. Clinical trial in 57 women undergoing CPT. Results. At baseline, in measuring quality of life for the EORTC QLQ-C30 questionnaire subscale of functionality, the worst scores for emotional function (55 points) and better social function (89 points) were observed. The symptom scales showed the worst pain averaged (66 points). The overall quality of life showed a low score (40 points). In the BR 23 module, low scores were observed in the field of future perspective (47 points). After treatment of lymphoedema, absolute reduction of excess volume between the upper limbs of 282 mL was observed, representing a reduction of 15%. No association was observed between the domains of quality of life and response to treatment of lymphoedema. Conclusion. This study included 57 women with advanced and chronic lymphoedema in early treatment with CPT and low scores for quality of life. The lymphoedema therapeutic response was not influenced by the QOL at the beginning of treatment. PMID- 26843989 TI - Identification and Characterization of the V(D)J Recombination Activating Gene 1 in Long-Term Memory of Context Fear Conditioning. AB - An increasing body of evidence suggests that mechanisms related to the introduction and repair of DNA double strand breaks (DSBs) may be associated with long-term memory (LTM) processes. Previous studies from our group suggested that factors known to function in DNA recombination/repair machineries, such as DNA ligases, polymerases, and DNA endonucleases, play a role in LTM. Here we report data using C57BL/6 mice showing that the V(D)J recombination-activating gene 1 (RAG1), which encodes a factor that introduces DSBs in immunoglobulin and T-cell receptor genes, is induced in the amygdala, but not in the hippocampus, after context fear conditioning. Amygdalar induction of RAG1 mRNA, measured by real time PCR, was not observed in context-only or shock-only controls, suggesting that the context fear conditioning response is related to associative learning processes. Furthermore, double immunofluorescence studies demonstrated the neuronal localization of RAG1 protein in amygdalar sections prepared after perfusion and fixation. In functional studies, intra-amygdalar injections of RAG1 gapmer antisense oligonucleotides, given 1 h prior to conditioning, resulted in amygdalar knockdown of RAG1 mRNA and a significant impairment in LTM, tested 24 h after training. Overall, these findings suggest that the V(D)J recombination activating gene 1, RAG1, may play a role in LTM consolidation. PMID- 26843993 TI - Autoextraction of Permanent Incisors and Self-Inflicted Orodental Trauma in a Severely Burned Child. AB - Autoextraction is one type of self-injurious behaviour. In the literature, self injurious behaviours are observed in syndromes and genetic conditions. However, to the best of our knowledge, SIB and autoextraction in a severely burned patient have not been reported to date. This report describes the self-inflicted trauma and autoextraction in a severely burned child, and the management of the child during and after burn treatment. PMID- 26843994 TI - Early Morphokinetic Monitoring of Embryos after Intracytoplasmic Sperm Injection with Fresh Ejaculate Sperm in Nonmosaic Klinefelter Syndrome: A Different Presentation. AB - The patient was diagnosed with nonmosaic 47, XXY Klinefelter Syndrome with the AZF deletion absent and SRY+. The nonmosaic 47, XXY karyotype was confirmed on a skin biopsy chromosomal analysis. Using only ejaculate motile sperms, 11 oocytes underwent ICSI and were placed rapidly in a time lapse (Embryoscope (c)) with a specific culture dish. Biopsies were performed on six embryos on the 3rd day, and numerical chromosomal abnormalities were observed using the FISH test before transfer. PGS results were normal in only two embryos with normal morphokinetics in the Embryoscope. For clinical confirmation of pregnancy, ultrasonographic examination was performed during the 7th week of pregnancy, and two gestational sacs and fetal heart beat were observed. PMID- 26843992 TI - Upper Limb Immobilisation: A Neural Plasticity Model with Relevance to Poststroke Motor Rehabilitation. AB - Advances in our understanding of the neural plasticity that occurs after hemiparetic stroke have contributed to the formulation of theories of poststroke motor recovery. These theories, in turn, have underpinned contemporary motor rehabilitation strategies for treating motor deficits after stroke, such as upper limb hemiparesis. However, a relative drawback has been that, in general, these strategies are most compatible with the recovery profiles of relatively high functioning stroke survivors and therefore do not easily translate into benefit to those individuals sustaining low-functioning upper limb hemiparesis, who otherwise have poorer residual function. For these individuals, alternative motor rehabilitation strategies are currently needed. In this paper, we will review upper limb immobilisation studies that have been conducted with healthy adult humans and animals. Then, we will discuss how the findings from these studies could inspire the creation of a neural plasticity model that is likely to be of particular relevance to the context of motor rehabilitation after stroke. For instance, as will be elaborated, such model could contribute to the development of alternative motor rehabilitation strategies for treating poststroke upper limb hemiparesis. The implications of the findings from those immobilisation studies for contemporary motor rehabilitation strategies will also be discussed and perspectives for future research in this arena will be provided as well. PMID- 26843991 TI - Abnormal Resting-State Functional Connectivity Strength in Mild Cognitive Impairment and Its Conversion to Alzheimer's Disease. AB - Individuals diagnosed with mild cognitive impairment (MCI) are at high risk of transition to Alzheimer's disease (AD). However, little is known about functional characteristics of the conversion from MCI to AD. Resting-state functional magnetic resonance imaging was performed in 25 AD patients, 31 MCI patients, and 42 well-matched normal controls at baseline. Twenty-one of the 31 MCI patients converted to AD at approximately 24 months of follow-up. Functional connectivity strength (FCS) and seed-based functional connectivity analyses were used to assess the functional differences among the groups. Compared to controls, subjects with MCI and AD showed decreased FCS in the default-mode network and the occipital cortex. Importantly, the FCS of the left angular gyrus and middle occipital gyrus was significantly lower in MCI-converters as compared with MCI nonconverters. Significantly decreased functional connectivity was found in MCI converters compared to nonconverters between the left angular gyrus and bilateral inferior parietal lobules, dorsolateral prefrontal and lateral temporal cortices, and the left middle occipital gyrus and right middle occipital gyri. We demonstrated gradual but progressive functional changes during a median 2-year interval in patients converting from MCI to AD, which might serve as early indicators for the dysfunction and progression in the early stage of AD. PMID- 26843995 TI - A Case of Idiopathic Acute Pancreatitis in the First Trimester of Pregnancy. AB - Acute pancreatitis is rare in pregnancy, with an estimated incidence of approximately 1 in 1000 to 1 in 10,000 pregnancies. Acute pancreatitis in pregnancy usually occurs in the third trimester. Here, we report a case of acute pancreatitis in the first trimester. A 36-year-old primigravida at 11 weeks of gestation complained of severe lower abdominal pain. The pain gradually worsened and migrated toward the epigastric region. She had no history of chronic alcoholism. Blood investigations showed elevated level of C-reactive protein (9.58 mg/dL), pancreatic amylase (170 IU/L), and lipase (332 IU/L). There was no gallstone and no abnormality in the pancreatic and biliary ducts on ultrasonography. Antinuclear antibody and IgG4 were negative and no evidence of hyperlipidemia or diabetes was found. There was also no evidence of viral infection. On the third day of hospitalization, she was diagnosed with severe acute pancreatitis on magnetic resonance imaging. Medical interventions were initiated with nafamostat mesilate and ulinastatin, and parenteral nutrition was administered through a central venous catheter. On the eighth day of hospitalization, her condition gradually improved with a decreased level of pancreatic amylase and the pain subsided. After conservative management, she did not have any recurrence during her pregnancy. PMID- 26843996 TI - Avoidance Behaviours and Missed Opportunities in a Case of Metastatic Squamous Cell Carcinoma. AB - We describe the case of a 96-year-old woman who presented with a large fungating squamous cell carcinoma on her neck. In the Western hemisphere, it is rare to see patients with advanced tumours at their first presentation. We summarise the events leading to her late presentation to the hospital and explore the contributing factors. These may have included avoidance behaviour secondary to fears and misconceptions about cancer treatment. We conclude that healthcare professionals should be aware of these factors, and every effort should be made to address hidden fears and misconceptions when caring for patients with terminal illnesses. This will allay the patients' anxiety, thereby enabling them to make an informed choice about their future care. PMID- 26843997 TI - Simultaneous Low- and High-Grade Primary Leiomyosarcomas in Two Separate Organs in a Thirty-Year Survivor of Hereditary Retinoblastoma. AB - Patients with hereditary retinoblastoma have a heightened risk of developing subsequent bone and soft tissue sarcomas, exacerbated by radiation and alkylating chemotherapy. Secondary leiomyosarcomas are rare. A 29-year-old patient with bilateral retinoblastoma history presented with concurrent, independent malignancies found to be Rb-suppressed uterine and Rb-positive bladder leiomyosarcomas. She had undergone both ifosfamide chemotherapy and radiation therapy but demonstrated rare simultaneous primary leiomyosarcomas not previously described in association with ifosfamide. This rare case underlines the protean genetic predisposition to malignancy in this patient population, heightening awareness of lifelong malignancy potential, and the necessity for continuous periodic screening. PMID- 26843990 TI - Emerging Roles of Filopodia and Dendritic Spines in Motoneuron Plasticity during Development and Disease. AB - Motoneurons develop extensive dendritic trees for receiving excitatory and inhibitory synaptic inputs to perform a variety of complex motor tasks. At birth, the somatodendritic domains of mouse hypoglossal and lumbar motoneurons have dense filopodia and spines. Consistent with Vaughn's synaptotropic hypothesis, we propose a developmental unified-hybrid model implicating filopodia in motoneuron spinogenesis/synaptogenesis and dendritic growth and branching critical for circuit formation and synaptic plasticity at embryonic/prenatal/neonatal period. Filopodia density decreases and spine density initially increases until postnatal day 15 (P15) and then decreases by P30. Spine distribution shifts towards the distal dendrites, and spines become shorter (stubby), coinciding with decreases in frequency and increases in amplitude of excitatory postsynaptic currents with maturation. In transgenic mice, either overexpressing the mutated human Cu/Zn superoxide dismutase (hSOD1(G93A)) gene or deficient in GABAergic/glycinergic synaptic transmission (gephyrin, GAD-67, or VGAT gene knockout), hypoglossal motoneurons develop excitatory glutamatergic synaptic hyperactivity. Functional synaptic hyperactivity is associated with increased dendritic growth, branching, and increased spine and filopodia density, involving actin-based cytoskeletal and structural remodelling. Energy-dependent ionic pumps that maintain intracellular sodium/calcium homeostasis are chronically challenged by activity and selectively overwhelmed by hyperactivity which eventually causes sustained membrane depolarization leading to excitotoxicity, activating microglia to phagocytose degenerating neurons under neuropathological conditions. PMID- 26843999 TI - Paliperidone Palmitate Associated with Necrotizing Deep Tissue Infection and Sepsis Requiring Surgical Intervention. AB - Long-acting injectable antipsychotics provide the delivery of medication over an extended period of time requiring administration typically only every 2 to 4 weeks. The side effect profile of a long-acting injectable antipsychotic is predictable and similar to the oral formulation. However, injection site reactions may occur with this novel delivery system. The risk of an injection site reaction may be greater with the repeated administration of a lipophilic decanoate formulation and include pain, development of indurations, and fibrosis. Severe complications from injection site reactions have rarely been described in the literature with newer agents. We report the first case of a patient prescribed paliperidone palmitate every 3 weeks that developed severe sepsis requiring vasopressors and intubation due to delayed relayed recognition of a necrotizing infection at an injection site. Clinicians should be alerted to screen for injection site reactions when there is an unknown source infection in a patient receiving a long-acting injectable antipsychotic. PMID- 26843998 TI - Fracture of the Tibial Baseplate in Bicompartmental Knee Arthroplasty. AB - Introduction. Bicompartmental knee arthroplasty (BKA) addresses combined medial and patellofemoral compartment osteoarthritis, which is relatively common, and has been proposed as a bridge between unicompartmental and total knee arthroplasty (TKA). Case Presentation. We present the case report of a young active man treated with BKA after unsuccessful conservative therapy. Four years later, loosening with fracture of the tibial baseplate was identified and the patient was revised to TKA. Discussion. Although our case is only the second fractured tibial baseplate to be reported, we believe that the modular titanium design, with two fixation pegs, is too thin to withstand daily cyclic loading powers. Light daily routine use, rather than high-impact sports, is therefore advised. Failures may also be related to the implant being an early generation and known to be technically complex, with too few implant sizes. We currently use TKA for the treatment of medial and patellofemoral compartment osteoarthritis. PMID- 26844000 TI - Polyarteritis Nodosa Presenting as Digital Gangrene and Breast Lesion following Exposure to Silicone Breast Implants. AB - Polyarteritis nodosa (PAN) is a rare systemic necrotizing vasculitis of small and medium sized arteries. We report a case of a 49-year old woman who presented with PAN following exposure to silicone breast implants. Although the relationship between silicone implants and connective tissue diseases has been investigated in the literature, no prior reports were found documenting PAN after silicone mammoplasty. While the pathogenesis of idiopathic PAN is not known yet, responsiveness to immunosuppressive therapy may suggest an immunologic mechanism. More robust research is needed to understand the connection between silicone breast implants and autoimmunity. PMID- 26844001 TI - Enucleation of a Giant Hemangioma of Liver: Old School Revisited. AB - Hemangiomas are the most frequent benign hepatic tumours and are usually found in patients aged between 40 and 60 years, more frequently in women. In 30-35% of patients, the lesions are multiple. If the lesions are larger than 4-10 cm, they are coined as "giant" hemangioma. Here, we present a case of giant hemangioma treated with enucleation of the lesion and the advantages of the procedure. PMID- 26844002 TI - Abscess Formation after Septic Arthritis in the Sternoclavicular Joint of Two Healthy Men. AB - Abscess formation after septic arthritis in the sternoclavicular joint is a rare phenomenon in healthy people without immune suppression, intravenous drug abuse, or diabetes. Here we report two cases with formation of abscess in two middle aged men, with no relevant comorbidities and no obvious sites of infection. The abscesses were both treated surgically with debridement followed by negative pressure wound therapy and antibiotics. The cases differ in diagnostic procedures and delay of diagnosis and broach the issues of handling a rare disease. PMID- 26844003 TI - Advanced Mesodermal (Mullerian) Adenosarcoma of the Ovary: Metastases to the Lungs, Mouth, and Brain. AB - Background. A malignant mixed Mullerian tumor (MMMT) is a malignant neoplasm found in the uterus, the ovaries, the fallopian tubes, and other parts of the body that contains both carcinomatous (epithelial tissue) and sarcomatous (connective tissue) components. Outcome of MMMTs is determined primarily by depth of invasion and stage. The metastatic background of these lesions is controversial and unknown. Case Report. A 75-year-old woman was admitted to the hospital with anorexia, weakness, and persistent coughing. The imaging exams revealed a solid, promiscuous lesion of 16 * 14 cm in dimensions located into the small pelvis, surrounding the uterus and the ovaries. The patient underwent exploratory laparotomy. The mass was removed and the histological examination of the specimen revealed an advanced mesodermal adenocarcinoma of the ovary (MMMT). Nine days after the operation the patient presented with metastatic lesions in the mouth as well as the lungs. Within a month after the discharge from the hospital metastatic lesions of the MMMT were also depicted in the CT brain scan. Conclusion. Despite the fact that sarcomas have a long-term metastatic potential, to our knowledge this is the first case of Mullerian adenosarcoma presenting with such extraperitoneal metastases. PMID- 26844004 TI - Presentation and Surgical Management of Duodenal Duplication in Adults. AB - Duodenal duplications in adults are exceedingly rare and their diagnosis remains difficult as symptoms are largely nonspecific. Clinical presentations include pancreatitis, biliary obstruction, gastrointestinal bleeding from ectopic gastric mucosa, and malignancy. A case of duodenal duplication in a 59-year-old female is presented, and her treatment course is reviewed with description of combined surgical and endoscopic approach to repair, along with a review of historic and current recommendations for management. Traditionally, gastrointestinal duplications have been treated with surgical resection; however, for duodenal duplications, the anatomic proximity to the biliopancreatic ampulla makes surgical management challenging. Recently, advances in endoscopy have improved the clinical success of cystic intraluminal duodenal duplications. Despite these advances, surgical resection is still recommended for extraluminal tubular duplications although combined techniques may be necessary for long tubular duplications. For duodenal duplications, a combined approach of partial excision combined with mucosal stripping may offer advantage. PMID- 26844005 TI - A Case of In-Bore Transperineal MRI-Guided Prostate Biopsy of a Patient with Ileal Pouch-Anal Anastomosis. AB - Ulcerative colitis (UC) is an inflammatory disease that specifically affects the colon. Ulcerative colitis is primarily treated medically and refractory disease is treated with proctocolectomy and ileal pouch-anal anastomosis (IPAA). Gastroenterologists advise against digital rectal exams, pelvic radiation therapy, and transrectal ultrasound (TRUS) biopsies of the prostates of ileal pouch-anal anastomosis patients. Any form of pouch manipulation can lead to severe bleeding, inflammation, and pain. Urologists are therefore faced with the challenge of doing a prostate biopsy without a transrectal ultrasound. We report the rare case of a patient with an ileal pouch-anal anastomosis who underwent in bore transperineal MRI-guided biopsy of the prostate. PMID- 26844007 TI - Collaborative Data Analytics with DataHub. AB - While there have been many solutions proposed for storing and analyzing large volumes of data, all of these solutions have limited support for collaborative data analytics, especially given the many individuals and teams are simultaneously analyzing, modifying and exchanging datasets, employing a number of heterogeneous tools or languages for data analysis, and writing scripts to clean, preprocess, or query data. We demonstrate DataHub, a unified platform with the ability to load, store, query, collaboratively analyze, interactively visualize, interface with external applications, and share datasets. We will demonstrate the following aspects of the DataHub platform: (a) flexible data storage, sharing, and native versioning capabilities: multiple conference attendees can concurrently update the database and browse the different versions and inspect conflicts; (b) an app ecosystem that hosts apps for various data processing activities: conference attendees will be able to effortlessly ingest, query, and visualize data using our existing apps; (c) thrift-based data serialization permits data analysis in any combination of 20+ languages, with DataHub as the common data store: conference attendees will be able to analyze datasets in R, Python, and Matlab, while the inputs and the results are still stored in DataHub. In particular, conference attendees will be able to use the DataHub notebook - an IPython-based notebook for analyzing data and storing the results of data analysis. PMID- 26844008 TI - Smart Drill-Down: A New Data Exploration Operator. AB - We present a data exploration system equipped with smart drill-down, a novel operator for interactively exploring a relational table to discover and summarize "interesting" groups of tuples. Each such group of tuples is represented by a rule. For instance, the rule (a, b, ?, 1000) tells us that there are a thousand tuples with value a in the first column and b in the second column (and any value in the third column). Smart drill-down presents an analyst with a list of rules that together describe interesting aspects of the table. The analyst can tailor the definition of interesting, and can interactively apply smart drill-down on an existing rule to explore that part of the table. In the demonstration, conference attendees will be able to use the data exploration system equipped with smart drill-down, and will be able to contrast smart drill-down to traditional drill down, for various interestingness measures, and resource constraints. PMID- 26844009 TI - Clomiphene Citrate Effectively Increases Testosterone in Obese, Young, Hypogonadal Men. AB - BACKGROUND: Obesity has been associated with low testosterone (T) in adult males and in pubertal boys. Therapy for hypogonadism with exogenous T may lead to testicular atrophy and later infertility. Only a few studies have demonstrated that the Selective Estrogen Receptor Modulator (SERM) clomiphene citrate (CC), an estrogen receptor antagonist, increases T in obese hypogonadal men while preventing testicular atrophy. No studies to date using CC have been done in younger obese post-pubertal hypogonadal males. OBJECTIVE: To determine whether CC therapy is effective in increasing serum T levels in hypogonadal post-pubertal obese males 18-21 years. MATERIALS AND METHODS: A retrospective chart analysis of records in obese men aged 18-21 years was done. Patients with early morning T level <350 ng/dl were given 25 mg CC on alternate days. Out of 18 patients found to have low T, 11 were analyzed. Baseline serum T, LH, FSH, weight and BMI were compared at baseline and after 3 months of CC treatment. RESULTS: Baseline T level was 233 +/- 66 ng/dl and increased to 581 +/- 161 ng/dl (p<0.0001) after 3 months of CC treatment. Baseline LH levels increased from 3.3 +/- 1.6 mIU/mL to 5.7 +/- 1.7 mIU/mL (p=0.027). Similarly, baseline FSH levels increased from 2.8 +/- 1.5 mIU/mL to 6.2 +/- 3 mIU/mL after CC treatment (p=0.026). There was no correlation between baseline or post treatment weight or BMI and the T level, LH, or FSH level. CONCLUSION: This is the first study reporting on CC therapy in obese, hypogonadal post-pubertal men 18-21 years. The SERM CC increased T in obese post-pubertal hypogonadal men, similar to efficacy of CC in adult hypogonadal men over the age 21 years. Larger randomized controlled studies to study the safety and potential use of CC to improve T in young obese HG men are needed. PMID- 26844010 TI - A Tutorial on RxODE: Simulating Differential Equation Pharmacometric Models in R. AB - This tutorial presents the application of an R package, RxODE, that facilitates quick, efficient simulations of ordinary differential equation models completely within R. Its application is illustrated through simulation of design decision effects on an adaptive dosing regimen. The package provides an efficient, versatile way to specify dosing scenarios and to perform simulation with variability with minimal custom coding. Models can be directly translated to Rshiny applications to facilitate interactive, real-time evaluation/iteration on simulation scenarios. PMID- 26844006 TI - Recent advances in biosynthesis of bioactive compounds in traditional Chinese medicinal plants. AB - Plants synthesize and accumulate large amount of specialized (or secondary) metabolites also known as natural products, which provide a rich source for modern pharmacy. In China, plants have been used in traditional medicine for thousands of years. Recent development of molecular biology, genomics and functional genomics as well as high-throughput analytical chemical technologies has greatly promoted the research on medicinal plants. In this article, we review recent advances in the elucidation of biosynthesis of specialized metabolites in medicinal plants, including phenylpropanoids, terpenoids and alkaloids. These natural products may share a common upstream pathway to form a limited numbers of common precursors, but are characteristic in distinct modifications leading to highly variable structures. Although this review is focused on traditional Chinese medicine, other plants with a great medicinal interest or potential are also discussed. Understanding of their biosynthesis processes is critical for producing these highly value molecules at large scale and low cost in microbes and will benefit to not only human health but also plant resource conservation. PMID- 26844011 TI - Weight-HbA1c-insulin-glucose model for describing disease progression of type 2 diabetes. AB - A previous semi-mechanistic model described changes in fasting serum insulin (FSI), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) in patients with type 2 diabetic mellitus (T2DM) by modeling insulin sensitivity and beta cell function. It was later suggested that change in body weight could affect insulin sensitivity, which this study evaluated in a population model to describe the disease progression of T2DM. Nonlinear mixed effects modeling was performed on data from 181 obese patients with newly diagnosed T2DM managed with diet and exercise for 67 weeks. Baseline beta-cell function and insulin sensitivity were 61% and 25% of normal, respectively. Management with diet and exercise (mean change in body weight = -4.1 kg) was associated with an increase of insulin sensitivity (30.1%) at the end of the study. Changes in insulin sensitivity were associated with a decrease of FPG (range, 7.8-7.3 mmol/L) and HbA1c (6.7-6.4%). Weight change as an effector on insulin sensitivity was successfully evaluated in a semi-mechanistic population model. PMID- 26844013 TI - Elucidating Differences in the Hepatotoxic Potential of Tolcapone and Entacapone With DILIsym((r)), a Mechanistic Model of Drug-Induced Liver Injury. AB - Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors developed as adjunct therapies for treating Parkinson's disease. While both drugs have been shown to cause mitochondrial dysfunction and inhibition of the bile salt export protein (BSEP), liver injury has only been associated with the use of tolcapone. Here we used a multiscale, mechanistic model (DILIsym((r))) to simulate the response to tolcapone and entacapone. In a simulated population (SimPopsTM) receiving recommended doses of tolcapone (200 mg t.i.d.), increases in serum alanine transaminase (ALT) >3* the upper limit of normal (ULN) were observed in 2.2% of the population. In contrast, no simulated patients receiving recommended doses of entacapone (200 mg 8* day) experienced serum ALT >3* ULN. Further, DILIsym((r)) analyses revealed patient-specific risk factors that may contribute to tolcapone-mediated hepatotoxicity. In summary, the simulations demonstrated that differences in mitochondrial uncoupling potency and hepatic exposure primarily account for the difference in hepatotoxic potential for tolcapone and entacapone. PMID- 26844012 TI - Semiphysiologically based pharmacokinetic model for midazolam and CYP3A mediated metabolite 1-OH-midazolam in morbidly obese and weight loss surgery patients. AB - This study aimed to describe the pharmacokinetics of midazolam and its cytochrome P450 3A (CYP3A) mediated metabolite 1-OH-midazolam in morbidly obese patients receiving oral and i.v. midazolam before (n = 20) and one year after weight loss surgery (n = 18), thereby providing insight into the influence of weight loss surgery on CYP3A activity in the gut wall and liver. In a semiphysiologically based pharmacokinetic (semi-PBPK) model in which different blood flow scenarios were evaluated, intrinsic hepatic clearance of midazolam (CLint,H) was 2 (95% CI 1.40-1.64) times higher compared to morbidly obese patients before surgery (P < 0.01). Midazolam gut wall clearance (CLint,G) was slightly lower in patients after surgery (P > 0.05), with low values for both groups. The results of the semi-PBPK model suggest that, in patients after weight loss surgery, CYP3A hepatic metabolizing capacity seems to recover compared to morbidly obese patients, whereas CYP3A mediated CLint,G was low for both populations and showed large interindividual variability. PMID- 26844014 TI - Designing conservation strategies to preserve the genetic diversity of Astragalus edulis Bunge, an endangered species from western Mediterranean region. AB - Astragalus edulis (Fabaceae) is an endangered annual species from the western Mediterranean region that colonized the SE Iberian Peninsula, NE and SW Morocco, and the easternmost Macaronesian islands (Lanzarote and Fuerteventura). Although in Spain some conservation measures have been adopted, it is still necessary to develop an appropriate management plan to preserve genetic diversity across the entire distribution area of the species. Our main objective was to use population genetics as well as ecological and phylogeographic data to select Relevant Genetic Units for Conservation (RGUCs) as the first step in designing conservation plans for A. edulis. We identified six RGUCs for in situ conservation, based on estimations of population genetic structure and probabilities of loss of rare alleles. Additionally, further population parameters, i.e. occupation area, population size, vulnerability, legal status of the population areas, and the historical haplotype distribution, were considered in order to establish which populations deserve conservation priority. Three populations from the Iberian Peninsula, two from Morocco, and one from the Canary Islands represent the total genetic diversity of the species and the rarest allelic variation. Ex situ conservation is recommended to complement the preservation of A. edulis, given that effective in situ population protection is not feasible in all cases. The consideration of complementary phylogeographic and ecological data is useful for management efforts to preserve the evolutionary potential of the species. PMID- 26844015 TI - Assessing conservation status of resident and migrant birds on Hispaniola with mist-netting. AB - We analyzed temporal trends in mist-net capture rates of resident (n = 8) and overwintering Nearctic-Neotropical migrant (n = 3) bird species at two sites in montane broadleaf forest of the Sierra de Bahoruco, Dominican Republic, with the goal of providing quantitative information on population trends that could inform conservation assessments. We conducted sampling at least once annually during the winter months of January-March from 1997 to 2010. We found evidence of declines in capture rates for three resident species, including one species endemic to Hispaniola. Capture rate of Rufous-throated Solitaire (Myadestes genibarbis) declined by 3.9% per year (95% CL = 0%, 7.3%), Green-tailed Ground-Tanager (Microligea palustris) by 6.8% (95% CL = 3.9%, 8.8%), and Greater Antillean Bullfinch (Loxigilla violacea) by 4.9% (95% CL = 0.9%, 9.2%). Two rare and threatened endemics, Hispaniolan Highland-Tanager (Xenoligea montana) and Western Chat-Tanager (Calyptophilus tertius), showed statistically significant declines, but we have low confidence in these findings because trends were driven by exceptionally high capture rates in 1997 and varied between sites. Analyses that excluded data from 1997 revealed no trend in capture rate over the course of the study. We found no evidence of temporal trends in capture rates for any other residents or Nearctic-Neotropical migrants. We do not know the causes of the observed declines, nor can we conclude that these declines are not a purely local phenomenon. However, our findings, along with other recent reports of declines in these same species, suggest that a closer examination of their conservation status is warranted. Given the difficulty in obtaining spatially extensive, long term estimates of population change for Hispaniolan birds, we suggest focusing on other metrics of vulnerability that are more easily quantified yet remain poorly described, such as extent of occurrence. PMID- 26844016 TI - Mining integrated semantic networks for drug repositioning opportunities. AB - Current research and development approaches to drug discovery have become less fruitful and more costly. One alternative paradigm is that of drug repositioning. Many marketed examples of repositioned drugs have been identified through serendipitous or rational observations, highlighting the need for more systematic methodologies to tackle the problem. Systems level approaches have the potential to enable the development of novel methods to understand the action of therapeutic compounds, but requires an integrative approach to biological data. Integrated networks can facilitate systems level analyses by combining multiple sources of evidence to provide a rich description of drugs, their targets and their interactions. Classically, such networks can be mined manually where a skilled person is able to identify portions of the graph (semantic subgraphs) that are indicative of relationships between drugs and highlight possible repositioning opportunities. However, this approach is not scalable. Automated approaches are required to systematically mine integrated networks for these subgraphs and bring them to the attention of the user. We introduce a formal framework for the definition of integrated networks and their associated semantic subgraphs for drug interaction analysis and describe DReSMin, an algorithm for mining semantically-rich networks for occurrences of a given semantic subgraph. This algorithm allows instances of complex semantic subgraphs that contain data about putative drug repositioning opportunities to be identified in a computationally tractable fashion, scaling close to linearly with network data. We demonstrate the utility of our approach by mining an integrated drug interaction network built from 11 sources. This work identified and ranked 9,643,061 putative drug-target interactions, showing a strong correlation between highly scored associations and those supported by literature. We discuss the 20 top ranked associations in more detail, of which 14 are novel and 6 are supported by the literature. We also show that our approach better prioritizes known drug target interactions, than other state-of-the art approaches for predicting such interactions. PMID- 26844017 TI - Non-native species in the vascular flora of highlands and mountains of Iceland. AB - The highlands and mountains of Iceland are one of the largest remaining wilderness areas in Europe. This study aimed to provide comprehensive and up-to date data on non-native plant species in these areas and to answer the following questions: (1) How many non-native vascular plant species inhabit highland and mountainous environments in Iceland? (2) Do temporal trends in the immigration of alien species to Iceland differ between highland and lowland areas? (3) Does the incidence of alien species in the disturbed and undisturbed areas within Icelandic highlands differ? (4) Does the spread of non-native species in Iceland proceed from lowlands to highlands? and (5) Can we detect hot-spots in the distribution of non-native taxa within the highlands? Overall, 16 non-native vascular plant species were detected, including 11 casuals and 5 naturalized taxa (1 invasive). Results showed that temporal trends in alien species immigration to highland and lowland areas are similar, but it is clear that the process of colonization of highland areas is still in its initial phase. Non-native plants tended to occur close to man-made infrastructure and buildings including huts, shelters, roads etc. Analysis of spatio-temporal patterns showed that the spread within highland areas is a second step in non-native plant colonization in Iceland. Several statically significant hot spots of alien plant occurrences were identified using the Getis-Ord Gi* statistic and these were linked to human disturbance. This research suggests that human-mediated dispersal is the main driving force increasing the risk of invasion in Iceland's highlands and mountain areas. PMID- 26844018 TI - Analysis of five complete genome sequences for members of the class Peribacteria in the recently recognized Peregrinibacteria bacterial phylum. AB - Five closely related populations of bacteria from the Candidate Phylum (CP) Peregrinibacteria, part of the bacterial Candidate Phyla Radiation (CPR), were sampled from filtered groundwater obtained from an aquifer adjacent to the Colorado River near the town of Rifle, CO, USA. Here, we present the first complete genome sequences for organisms from this phylum. These bacteria have small genomes and, unlike most organisms from other lineages in the CPR, have the capacity for nucleotide synthesis. They invest significantly in biosynthesis of cell wall and cell envelope components, including peptidoglycan, isoprenoids via the mevalonate pathway, and a variety of amino sugars including perosamine and rhamnose. The genomes encode an intriguing set of large extracellular proteins, some of which are very cysteine-rich and may function in attachment, possibly to other cells. Strain variation in these proteins is an important source of genotypic variety. Overall, the cell envelope features, combined with the lack of biosynthesis capacities for many required cofactors, fatty acids, and most amino acids point to a symbiotic lifestyle. Phylogenetic analyses indicate that these bacteria likely represent a new class within the Peregrinibacteria phylum, although they ultimately may be recognized as members of a separate phylum. We propose the provisional taxonomic assignment as 'Candidatus Peribacter riflensis', Genus Peribacter, Family Peribacteraceae, Order Peribacterales, Class Peribacteria in the phylum Peregrinibacteria. PMID- 26844019 TI - Cross-platform normalization of microarray and RNA-seq data for machine learning applications. AB - Large, publicly available gene expression datasets are often analyzed with the aid of machine learning algorithms. Although RNA-seq is increasingly the technology of choice, a wealth of expression data already exist in the form of microarray data. If machine learning models built from legacy data can be applied to RNA-seq data, larger, more diverse training datasets can be created and validation can be performed on newly generated data. We developed Training Distribution Matching (TDM), which transforms RNA-seq data for use with models constructed from legacy platforms. We evaluated TDM, as well as quantile normalization, nonparanormal transformation, and a simple log 2 transformation, on both simulated and biological datasets of gene expression. Our evaluation included both supervised and unsupervised machine learning approaches. We found that TDM exhibited consistently strong performance across settings and that quantile normalization also performed well in many circumstances. We also provide a TDM package for the R programming language. PMID- 26844020 TI - Rupture of distal anterior cerebral artery aneurysm presenting only subdural hemorrhage without subarachnoid hemorrhage: a case report. AB - Intracranial aneurysm rupture usually manifests with subarachnoid hemorrhage, often combined with intracerebral hemorrhage with intraventricular hemorrhage extension. In rare cases, however, these aneurysms present only as subdural hematomas. Recently, we treated a 48-years-old female patient who presented only with subdural hematoma. Interestingly, she did not have a history of trauma. Computed tomography angiography and digital subtraction angiography revealed a 5 * 3 mm sized aneurysm at the A3-A4 junction of the left anterior cerebral artery. On admission, emergency operation (clipping and hematoma evacuation) was performed to protect against re-bleeding. Along with postoperative intensive care, the patient returned to normal daily life with only a mild headache. Given that patients may present with atraumatic acute subdural hematoma, the clinician must bear in mind the possibility of intracranial vascular pathology and obtain angiographic scans to evaluate for any underlying conditions to prevent patient deaths. PMID- 26844021 TI - Analysis of bacterial communities associated with potting media. AB - BACKGROUND: Potting media are commonly used by growers in different parts of the world for potted plants, raising seedlings and for improving soil characteristics. This study was conducted to characterize bacterial communities occurring in 13 commercial potting media products originating from seven countries. FINDINGS: Bacteria were isolated using serial dilution. Identification to the species level was based on phylogenetic analysis of the 16S rRNA gene. The analysis showed the association of 13 bacterial species with the different potting media samples, namely Arthrobacter livingstonensis, Kocuria flava, Leifsonia lichenia, Bacillus vallismortis, Bacillus pumilus, Staphylococcus warneri, Burkholderia phenazinium, Burkholderia sp., Ralstonia pickettii, Rhodanobacter spathiphylli, Rhodanobacter sp., Pseudomonas thivervalensis and Chryseobacterium gallinarum. Bacterial densities in the samples ranged from 8 * 10(7) to 1.2 * 10(9) colony forming units per gram of substrate. CONCLUSIONS: The study shows the isolation of some potential plant and human bacterial pathogens. However, most of the isolated species were either biocontrol species or saprophytes. The study questions the ways by which these bacterial species were introduced into potting media. To the best of our knowledge, this appears to be the first report of most of the isolated bacteria from potting media, except B. pumilus. PMID- 26844022 TI - Short-term assessment of BCR repertoires of SLE patients after high dose glucocorticoid therapy with high-throughput sequencing. AB - We analyze and assess BCR repertoires of SLE patients before and after high dose glucocorticoid therapy to address two fundamental questions: (1) After the treatment, how the BCR repertoire of SLE patient change on the clone level? (2) How to screen putative autoantibody clone set from BCR repertoire of SLE patients? The PBMCs of two SLE patients (P1 and P2) at different time points were collected, and DNA of these samples were extracted. High-throughput sequencing technology was applied in detection of BCR repertoire. Finally, we used bioinformatic methodology to analyse sequence data. We found that these two patients lost some IGHV3 family genes usage after treatment compared with before treatment. For pairing of IGHV-IGHJ gene, no significant change was shown for each patient. In addition, analyses of the composition of H-CDR3 showed overall AA compositions of H-CDR3 at three time points in each SLE patients were very similar, and the results of H-CDR3 AA usage that had the same length (14 AA) and the same position were similar. Antinuclear antibody tests of SLE patients showed that level of some antinuclear antibodies reduced after treatment; however, there was no sign that the percentage of autoantibody clones in BCR repertoires would reduce. High dose glucocorticoid treatment in short term will have little impact on composition of BCR repertoire of SLE patient. Treatment can reduce the amount of autoantibody in the protein level, but may not reduce the percentage of autoantibody clones in BCR repertoire in the clonal level. PMID- 26844024 TI - More results on Simpson's type inequality through convexity for twice differentiable continuous mappings. AB - Our aim in this article is to incorporate the notion of "strongly s-convex function" and prove a new integral identity. Some new inequalities of Simpson type for strongly s-convex function utilizing integral identity and Holder's inequality are considered. PMID- 26844023 TI - Half-marathoners are younger and slower than marathoners. AB - Age and performance trends of elite and recreational marathoners are well investigated, but not for half-marathoners. We analysed age and performance trends in 508,108 age group runners (125,894 female and 328,430 male half marathoners and 10,205 female and 43,489 male marathoners) competing between 1999 and 2014 in all flat half-marathons and marathons held in Switzerland using single linear regression analyses, mixed-effects regression analyses and analyses of variance. The number of women and men increased across years in both half marathons and marathons. There were 12.3 times more female half-marathoners than female marathoners and 7.5 times more male half-marathoners than male marathoners. For both half-marathons and marathons, most of the female and male finishers were recorded in age group 40-44 years. In half-marathons, women (10.29 +/- 3.03 km/h) were running 0.07 +/- 0.06 km/h faster (p < 0.001) than men (10.22 +/- 3.06 km/h). Also in marathon, women (14.77 +/- 4.13 km/h) were running 0.28 +/- 0.16 km/h faster (p < 0.001) than men (14.48 +/- 4.07 km/h). In marathon, women (42.18 +/- 10.63 years) were at the same age than men (42.06 +/- 10.45 years) (p > 0.05). Also in half-marathon, women (41.40 +/- 10.63 years) were at the same age than men (41.31 +/- 10.30 years) (p > 0.05). However, women and men marathon runners were older than their counterpart half-marathon runners (p < 0.001). In summary, (1) more athletes competed in half-marathons than in marathons, (2) women were running faster than men, (3) half-marathoners were running slower than marathoners, and (4) half-marathoners were younger than marathoners. PMID- 26844025 TI - Evolutionary approach to violating group anonymity using third-party data. AB - In the era of Big Data, it is almost impossible to completely restrict access to primary non-aggregated statistical data. However, risk of violating privacy of individual respondents and groups of respondents by analyzing primary data has not been reduced. There is a need in developing subtler methods of data protection to come to grips with these challenges. In some cases, individual and group privacy can be easily violated, because the primary data contain attributes that uniquely identify individuals and groups thereof. Removing such attributes from the dataset is a crude solution and does not guarantee complete privacy. In the field of providing individual data anonymity, this problem has been widely recognized, and various methods have been proposed to solve it. In the current work, we demonstrate that it is possible to violate group anonymity as well, even if those attributes that uniquely identify the group are removed. As it turns out, it is possible to use third-party data to build a fuzzy model of a group. Typically, such a model comes in a form of a set of fuzzy rules, which can be used to determine membership grades of respondents in the group with a level of certainty sufficient to violate group anonymity. In the work, we introduce an evolutionary computing based method to build such a model. We also discuss a memetic approach to protecting the data from group anonymity violation in this case. PMID- 26844026 TI - On bounds in Poisson approximation for distributions of independent negative binomial distributed random variables. AB - Using the Stein-Chen method some upper bounds in Poisson approximation for distributions of row-wise triangular arrays of independent negative-binomial distributed random variables are established in this note. PMID- 26844027 TI - Electron mobility in semi-metal HgCdTe quantum wells: dependence on the well width. AB - Energy spectra, carrier concentration and electron mobility are numerically modeled in intrinsic and n-type semi-metal HgCdTe quantum wells at T = 77 K. We present results for the electron mobility calculated in a model incorporating electron scattering on longitudinal optical phonons, charged impurities, and holes, and including the 2D electron gas screening for all mentioned scattering mechanisms. Inelasticity of electron-phonon scattering is treated by means of a direct iterative solution of Boltzmann transport equation. Comparison with the experimental data at liquid helium temperature is provided. PMID- 26844028 TI - Evaluating a decision making system for cardiovascular dysautonomias diagnosis. AB - Autonomic nervous system (ANS) is the part of the nervous system that is involved in homeostasis of the whole body functions. A malfunction in this system can lead to a cardiovascular dysautonomias. Hence, a set of dynamic tests are adopted in ANS units to diagnose and treat patients with cardiovascular dysautonomias. The purpose of this study is to develop and evaluate a decision tree based cardiovascular dysautonomias prediction system on a dataset collected from the ANS unit of the Moroccan university hospital Avicenne. We collected a dataset of 263 records from the ANS unit of the Avicenne hospital. This dataset was split into three subsets: training set (123 records), test set (55 records) and validation set (85 records). C4.5 decision tree algorithm was used in this study to develop the prediction system. Moreover, Java Enterprise Edition platform was used to implement a prototype of the developed system which was deployed in the Avicenne ANS unit so as to be clinically validated. The performance of the decision tree-based prediction system was evaluated by means of the error rate criterion. The error rates were measured for each classifier and have achieved an average value of 1.46, 2.24 and 0.89 % in training, test, and validation sets respectively. The results obtained were encouraging but further replicated studies are still needed to be performed in order to confirm the findings of this study. PMID- 26844030 TI - In-service teachers' perceptions of project-based learning. AB - The study analyses teachers' perceptions of methods, teacher roles, success and evaluation in PBL and traditional classroom instruction. The analysis is based on empirical data collected in primary schools and vocational secondary schools. An analysis of 109 questionnaires revealed numerous differences based on degree of experience and type of school. In general, project-based methods were preferred among teachers, who mostly perceived themselves as facilitators and considered motivation and transmission of values central to their work. Teachers appeared not to capitalize on the use of ICT tools or emotions. Students actively participated in the evaluation process via oral evaluation. PMID- 26844029 TI - Risk of cancer-specific, cardiovascular, and all-cause mortality among Asian and Pacific Islander breast cancer survivors in the United States, 1991-2011. AB - Asian and Pacific Islander (API) women in the United States (U.S.) are a heterogeneous group reported to have better prognosis after breast cancer (BC) compared to their Non-Hispanic White (NHW) counterparts. Few studies have examined differences in BC survival between individual API ethnic groups. We conducted a retrospective cohort study of 462,005 NHW and 44,531 API women diagnosed with incident, stage I-III BC between 1991 and 2011 in the Surveillance, Epidemiology and End Results (SEER) 18 registries. SEER-reported API ethnicity was grouped as Chinese, Japanese, Filipino, Hawaiian, Korean, Vietnamese, Asian Indian and Pakistani, and Pacific Islander. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for risk of BC-specific, cardiovascular and all-cause mortality comparing API to NHW women. We also estimated mortality risk comparing U.S.-born to non-U.S.-born women. Compared to NHW women, API women overall had lower BC-specific, cardiovascular and all-cause mortality. BC-specific mortality risk was lowest among Japanese women (HR 0.69, 95 % CI 0.63-0.77). Other women had similar (Filipino, HR 0.93, 0.86-1.00; Hawaiian, HR 1.01, 0.89-1.17) or greater (Pacific Islander, HR 1.44, 1.17-1.78) risk of BC-specific death. Compared to non-U.S. born API women, findings were suggestive of increased cardiovascular (HR 1.12, 1.03-1.20) and all-cause mortality (HR 1.29, 1.08-1.54) among U.S.-born API women. Mortality risk varies greatly between BC survivors from different API backgrounds. Further research is warranted to understand these disparities in BC survivorship and the social and cultural factors that possibly contribute to greater mortality among later-generation API women born in the United States. PMID- 26844031 TI - Development and feasibility of a mobile experience sampling application for tracking program implementation in youth well-being programs. AB - Well-being program evaluations mostly focus on identifying effective outcomes rather than measuring the actual extent to which program participants may apply learned skills in subsequent everyday lives. This study examined the feasibility of using a newly developed mobile experience sampling app called Wuzzup to study program implementation in young people participating in well-being programs. Ninety-six participants (60 females; 36 males) between the ages of 13 and 15 years (M = 13.87, SD = 0.71) were recruited to respond to two random prompts each day, for 7 days, at each of the three data collection time-points. Responses from 69 participants (72 % of initial sample) that met study criteria were retained for analysis. The average response rate was 92.89 %, with an average of 85.92 s to complete each ESM survey. Significant associations between first and second halves of the ESM week, and their respective positive affect and negative affect survey responses, demonstrate internal reliability and construct validity of the Wuzzup app to capture momentary affect and activation states of young people. This study also demonstrated the feasibility and practical utility of the Wuzzup app to profile and track an individual's learning over time. PMID- 26844032 TI - Is there a need for a new journal devoted to preventive medicine? PMID- 26844033 TI - Safety vs. efficacy assessment of pharmaceuticals: Epistemological rationales and methods. AB - In their comparative analysis of Randomised Clinical Trials and observational studies, Papanikoloau et al. (2006) assert that "it may be unfair to invoke bias and confounding to discredit observational studies as a source of evidence on harms". There are two kinds of answers to the question why this is so. One is based on metaphysical assumptions, such as the problem of causal sufficiency, modularity and other statistical assumptions. The other is epistemological and relates to foundational issues and how they determine the constraints we put on evidence. I will address here the latter dimension and present recent proposals to amend evidence hierarchies for the purpose of safety assessment of pharmaceuticals; I then relate these suggestions to a case study: the recent debate on the causal association between paracetamol and asthma. The upshot of this analysis is that different epistemologies impose different constraints on the methods we adopt to collect and evaluate evidence; thus they grant "lower level" evidence on distinct grounds and at different conditions. Appreciating this state of affairs illuminates the debate on the epistemic asymmetry concerning benefits and harms and sets the basis for a foundational, as opposed to heuristic, justification of safety assessment based on heterogeneous evidence. PMID- 26844034 TI - Relationship between the objectively-assessed neighborhood area and activity behavior in Swiss youth. AB - BACKGROUND: Neighborhood attributes are modifiable determinants of physical activity (PA) and sedentary behavior (SB). We tested whether the objectively assessed built and social environment was associated with PA and SB in Swiss youth and whether sex, age and the socioeconomic position (Swiss-SEP) modified such associations. METHODS: We combined data of 1742 youth (ages 4 to 17) from seven studies conducted within Switzerland between 2005-2010. All youth provided accelerometer data and a home address, which was linked to objective environmental data and the Swiss-SEP-index. Associations between neighborhood attributes and PA were analyzed by multivariable multilevel regression analyses. RESULTS: The extent of green areas and building density was positively associated with PA in the total sample (p < 0.05). Factors representing centrally located areas, and more schoolchildren living nearby tended to increase PA in secondary schoolchildren, boys and those from lower-ranked socioeconomic areas. In primary schoolchildren, the extent of green areas was positively associated with PA (p = 0.05). Associations between neighborhood attributes and PA were more pronounced in youth from low socioeconomic areas. CONCLUSIONS: The results indicate that some associations between neighborhood attributes and PA differ by age, sex and socioeconomic area. This should be taken into account when planning interventions to increase childhood PA. PMID- 26844035 TI - Social determinants of HPV vaccination delay rationales: Evidence from the 2011 National Immunization Survey-Teen. AB - OBJECTIVE: To examine social variations in parental rationales for delaying or forgoing human papillomavirus vaccination in their U.S. adolescent children. METHODS: Using data from the 2011 National Immunization Survey-Teen, we estimated a series of binary logistic regression models to predict the odds of reporting (1) any vaccine delay (n = 25,229) and (2) specific rationales among parents who reported that they were "not likely at all" to vaccinate their teen (n = 9,964). RESULTS: The odds of not receiving a recommendation to vaccinate were higher in parents of boys (OR = 2.57; CI = 2.20-3.01). The odds of reporting a lack of knowledge were higher in parents who identified as Hispanic (OR = 1.39; CI = 1.11 1.72), Black (OR = 1.49; CI = 1.19-1.85), and other races (OR = 1.43; CI = 1.13 1.80) than parents who identified as non-Hispanic White. Socioeconomic disparities in parental rationales for delaying human papillomavirus vaccination in their teen children were sporadic and inconsistent. CONCLUSION: Our results suggest that interventions should focus on increasing information about the benefits of the human papillomavirus vaccine among parents of minority youth. Our findings also suggest that interventions targeting health care providers may be a useful strategy for improving vaccine uptake among adolescent males. PMID- 26844036 TI - Internet use associated with HIV testing in adults in a national sample: Findings from the National Health Interview Survey, 2009. AB - BACKGROUND: Routine Human Immunodeficiency Virus (HIV) testing is a CDC recommendation. Little is known about health information technology (HIT) use and HIV testing. PURPOSE: To assess the relationship between HIT use and HIV screening and determine whether self-perceived HIV risk modifies this association. METHODS: Data from the National Health Interview Survey were analyzed. The survey response rate was 65.4%. The outcome was self-report of HIV testing (Y/N). Independent variables were HIT use, self-perceived HIV risk, and socio-demographics. HIT use is defined as internet or chat room use for health information. Logistic regression tested the association between HIV testing and HIT. Crude and adjusted models are reported. RESULTS: Of participants with data on HIV testing (n = 26,745), 40% reported being HIV tested, 52% used internet, and 4.2% used chat rooms. Internet and chat users had greater odds ratios for HIV testing (OR 1.8 95% CI (1.7, 1.9) and OR 1.7 95% CI (1.4, 2.0), respectively). Adjusting for covariates, internet use remained associated with HIV testing OR 1.4 95% CI (1.2, 1.7), but chat use did not. Self-perceived HIV risk did not modify this model. CONCLUSION: Internet use was associated with higher odds of HIV testing in the general population. Promotion of HIV testing via online sources may benefit screening efforts. PMID- 26844038 TI - Association between number of doses per day, number of medications and patient's non-compliance, and frequency of readmissions in a multi-ethnic Asian population. AB - OBJECTIVE: To investigate whether number of doses per day and number of medications are significantly associated with the number of readmissions and to study the association of readmission frequency with other medical and socio demographic variables. METHODS: Retrospective cross-sectional study involving 432 patients who were readmitted within 15 days of previous hospital discharge between January 1, 2013 and March 31, 2013. Relevant medical records were collected from the national electronic databases of every public tertiary hospital in Singapore. Significant variables (p < 0.05) were identified using forward selection and modeled using generalized linear mixed models. RESULTS: A total of 649 unplanned readmissions were reviewed. At a multivariable level, number of readmission was significantly associated with the number of medications (p = 0.002) and number of doses per day (p = 0.003) after adjusting for race, liver disease, schizophrenia and non-compliance. CONCLUSION: Complex medication regimen (i.e. multiple medications and multiple doses per day) is a statistically significant predictor of number of readmissions. Simplifying therapeutic regimens with alternatives such as longer-acting or fixed-dose combination drugs may facilitate better patient adherence and reduce costly readmissions. PMID- 26844037 TI - Low socio-economic environmental determinants of children's physical activity in Coventry, UK: A Qualitative study in parents. AB - BACKGROUND: Children's physical activity (PA) is affected by socio-economic status (SES) and the environment. Children are not fully autonomous in their decision making; parental decisions thus affect how children utilise their surrounding environments for PA. The aim was to examine environmental influences on children's PA from a qualitative perspective in parents from low SES wards in Coventry, UK. METHOD: 59 parents of children in year 4 (aged 8-9years) completed the ALPHA environmental questionnaire. 16 of these parents took part in focus group discussions examining environmental facilitators and barriers to their child's PA (March-April, 2013). RESULTS: Emerging themes related to physical (i.e. poor access, safety and quality of the neighbourhood) and social environment (i.e. 'rough' neighbourhood due to crime and anti-social behaviour) influences on the PA behaviour of children. The parents believed these environmental factors resulted in the children engaging in greater sedentary activity (watching TV) indoors. The school environment was perceived as a supportive physical environment for children's PA behaviour. CONCLUSION: Parent's perceptions of an unsupportive physical and social environment restrict children's opportunities to play outside and be physically active and may lead to increased body fat (BF). Schools provide a supportive environment for children from low SES to be physically active in. PMID- 26844039 TI - Validity and reliability of questionnaires measuring physical activity self efficacy, enjoyment, social support among Hong Kong Chinese children. AB - BACKGROUND: Physical activity (PA) correlates have not been extensively studied in Hong Kong children. OBJECTIVE: The aim of this study is to assess the validity and reliability of translated scales to measure PA related self-efficacy, enjoyment and social support in Hong Kong Chinese children. METHODS: Sample 1 (n = 273, aged 8-12 years) was recruited (May-June, 2013) from two primary schools. Confirmatory factor analyses (CFA) were conducted to assess factorial validity. Criterion validity was assessed by correlating measured constructs with self reported PA. Cronbach's alpha was computed to assess scale internal consistency. The intraclass correlation coefficient (ICC) was performed to assess scale test retest reliability. Criterion validity was further examined in Sample 2 (n = 84, aged 8-12 years) from a third school by correlating measured constructs with objectively measured PA collected in September 2013 and February 2014. RESULTS: The CFA results supported the one-factor structure of the scales. All PA correlates were significantly (p < 0.01) associated with self-reported PA in Sample 1. Self-efficacy and enjoyment were significantly (p < 0.05) correlated with objectively measured PA in Sample 2. All the scales demonstrated acceptable internal consistency. All ICC values of the scales suggested acceptable test retest reliability. CONCLUSION: The results provide psychometric support for using the scales to measure PA correlates among Hong Kong Chinese children. PMID- 26844040 TI - Softening of monthly cigarette use in youth and the need to harden measures in surveillance. AB - OBJECTIVE: To assess changes in monthly smoking in its relationship to daily smoking and heavier smoking in high school seniors. Public health agencies often report only "current use" of cigarettes among youth as any use in the past 30 days, even though additional measures are collected. Monthly use is a crude and changing indicator. METHODS: Results from 1975 to 2013 from Monitoring The Future Project were plotted and analyzed by linear regression. RESULTS: From 1975 to 2013, the percentage of monthly smokers who smoked daily decreased by 29% (21.2 percentage points) and monthly smokers who smoked 10 + cigarettes/day dropped by 57% (28 percentage points); the percentage of daily smokers who smoked 10 + cigarettes/day decreased by 40% (26.5 percentage points). CONCLUSION: Additional measures of frequency and intensity of use of cigarettes and other tobacco/nicotine products need to be more regularly reported. These results indicate softening rather than hardening of "current smoking" and have important implications for tobacco surveillance and for tobacco research because of a) increased likelihood of quitting smoking, b) health effects of cigarette smoking, and c) similar and interacting issues related to measuring the use of all tobacco/nicotine products. PMID- 26844041 TI - Impact of tobacco control policies in hospitals: Evaluation of a national smoke free campus ban in Spain. AB - INTRODUCTION: On January 2, 2011, the Spanish government passed a new smoking law that banned smoking in hospital campuses. The objective of this study was to evaluate the implementation of smoke-free campuses in the hospitals of Catalonia based on both airborne particulate matter and observational data. METHODS: This cross-sectional study included the hospitals registered in the Catalan Network of Smoke-free Hospitals. We measured the concentration of particulate matter < 2.5 um in MUg/m(3) at different locations, both indoors and outdoors before (2009) and after (2011) the implementation of the tobacco law. During 2011, we also assessed smoke-free zone signage and indications of smoking in the outdoor areas of hospital campuses. RESULTS: The overall median particulate matter < 2.5 um concentration fell from 12.22 MUg/m(3) (7.80-19.76 MUg/m(3)) in 2009 to 7.80 MUg/m(3) (4.68-11.96 MUg/m(3)) in 2011. The smoke-free zone signage within the campus was moderately implemented after the legislation in most hospitals, and 55% of hospitals exhibited no indications of tobacco consumption around the grounds. CONCLUSIONS: After the law, particulate matter < 2.5 um concentrations were much below the values obtained before the law and below the annual guideline value recommended by the World Health Organization for outdoor settings (10 MUg/m(3)). Our data showed the feasibility of implementing a smoke-free campus ban and its positive effects. PMID- 26844042 TI - Association between leg length-to-height ratio and metabolic syndrome in Chinese children aged 3 to 6 years. AB - OBJECTIVE: The aim of this study is to investigate the association between leg length-to-height ratio (LLHR) and metabolic syndrome (MetS) among Chinese children. METHODS: 1236 children (619 obese and 617 nonobese children) aged 3-6 years participated in a cross-sectional survey in 2005 in Tianjin, China. Information on body adiposity, metabolic traits, and related covariates was obtained using a standardized protocol. LLHR was calculated as the ratio of leg length to stature. RESULTS: In the multivariable logistic regression analyses, compared with those in the lowest quartile, odds ratios (OR) and 95% confidence intervals (CI) of MetS among children in the second through the highest quartiles of LLHR Z-score were 0.89 (95% CI, 0.64-1.25), 0.45 (95% CI, 0.32-0.63), and 0.37 (95% CI, 0.26-0.53), respectively, (P for trend < 0.0001 across LLHR Z-score quartiles). Compared with children with both higher levels of LLHR and lower levels of adipose indices, the corresponding ORs of MetS for those with both lower levels of LLHR and higher levels of anthropometric indices were 4.51 (95% CI, 3.08-6.62) for BMI Z-score, 3.86 (95% CI, 2.60-5.73) for waist circumference, and 2.75 (95% CI, 1.85-4.10) for waist-to-hip ratio, respectively. CONCLUSIONS: Greater LLHR is inversely associated with MetS in Chinese children. PMID- 26844043 TI - Using the risk behaviour diagnosis scale to understand Australian Aboriginal smoking - A cross-sectional validation survey in regional New South Wales. AB - OBJECTIVE: To validate, for the first time, the Risk Behaviour Diagnosis (RBD) Scale for Aboriginal Australian tobacco smokers, based on the Extended Parallel Process Model (EPPM). Despite high smoking prevalence, little is known about how Indigenous peoples assess their smoking risks. METHODS: In a cross-sectional study of 121 aboriginal smokers aged 18-45 in regional New South Wales, in 2014, RBD subscales were assessed for internal consistency. Scales included measures of perceived threat (susceptibility to and severity of smoking risks) and perceived efficacy (response efficacy and self-efficacy for quitting). An Aboriginal community panel appraised face and content validity. EPPM constructs of danger control (protective motivation) and fear control (defensive motivation) were assessed for cogency. RESULTS: Scales had acceptable to good internal consistency (Cronbach's alpha = 0.65-1.0). Most participants demonstrated high-perceived threat (77%, n = 93); and half had high-perceived efficacy (52%, n = 63). High perceived efficacy with high-threat appeared consistent with danger control dominance; low-perceived efficacy with high-threat was consistent with fear control dominance. CONCLUSIONS: In these Aboriginal smokers of reproductive age, the RBD Scale appeared valid and reliable. Further research is required to assess whether the RBD Scale and EPPM can predict quit attempts and assist with tailored approaches to counselling and targeted health promotion campaigns. PMID- 26844044 TI - The relevance of positive approaches to health for patient-centered care medicine. AB - Over the last centuries, the field of medicine has evolved from a disease oriented model where individuals were seen as simple hosts for diseases, to a patient-centered approach where health professionals actively try to engage their patients in treatment decision-making. This deep change in models of care acknowledges that patients are important actors in health fulfillment. Even though this change in models of care was a major step forward for medical practices and treatment success, patient-centered care medicine (PCCM) has brought its own limitations. In this brief comment, the concept of PCCM will be defined and the benefits of this model of care will be highlighted. The limitations inherent to PCCM will also be summarized. A discussion on how PCCM can move forward will be undertaken using evidence-based knowledge on positive approaches to health. Finally, an encompassing perspective (i.e. the salutogenic perspective) will il lustrate how the PCCM model of care can help to operationalize major health conceptual frameworks worldwide. PMID- 26844045 TI - What we might accomplish by engaging in our local communities. AB - OBJECTIVE: To describe the potential benefits of a clinician engaging in the same community in which her/his patients live. METHODS: Using a commentary format, the author describes the potential benefits of having clinicians engage in the same community in which her/his patients live. RESULTS: When we, clinicians, spend time in the same communities where our patients live, we have the opportunity to enhance our patients' lives and our teaching in three key ways. For one, we bring our medical expertise into the community. Secondly, we bring our expertise back to our practice and research inquiries. Finally, we teach trainees, who tend to be transient, about community assets and challenges. CONCLUSION: As we learn more about the importance of social determinants of health-describing how poverty, neighborhood, access to healthy food, and education, all play important roles in health-having an educator who can teach about the specific local community assets and influences on health may be as important as teaching which antibiotic to use. Academia and funders could increase this kind of knowledge acquisition and dissemination by rewarding and valuing these clinicians. PMID- 26844046 TI - Cancer screening among a population-based sample of insured women. AB - PURPOSE: Screening has been shown to lower the morbidity and mortality for breast, cervical, and colorectal cancers. Despite the availability of cancer screening, nearly 70,000 women die each year from these cancers. We conducted a study in 2008 within a privately-insured patient population of women who were members of an integrated health care system in Southeastern Michigan, for whom information on ovarian cancer risk as well as personal and family history of cancer was available. METHODS: We used a population-based, weighted stratified random sample of women from a single health care institution to assess the proportion with up-to-date breast, cervical, and colorectal screening. Multivariable analyses were conducted to identify predictors of screening behavior. RESULTS: In our study, women reported cervical and breast cancer screening above 90% and colorectal cancer screening above 75%. CONCLUSIONS: The results of our study hold promise that Healthy People 2020 cancer screening objectives might be obtainable as access to health insurance is expanded among US residents. PMID- 26844048 TI - The economic burden of eating disorders and related mental health comorbidities: An exploratory analysis using the U.S. Medical Expenditures Panel Survey. AB - BACKGROUND: Very little is known about the economic burden of eating disorders (ED) and related mental health comorbidities. METHODS: Using 5 years of data from the U.S. Medical Expenditures Panel Survey, we estimated the difference in annual health care costs, employment status, and earned income (2011 US$) between individuals with current ED compared to those without ED. We further estimated the contribution of mental health comorbidities to these disparities in health care costs, employment and earnings. RESULTS: Individuals with ED had greater annual health care costs ($1869, p = 0.012), lower but borderline significant employment rates (OR = 0.67, 95% CIs [0.41, 1.09]), and lower but not statistically significant earnings among those who were employed ($2093, p = 0.48), compared to individuals without ED. Among individuals with ED, the presence of mental health comorbidities was associated with higher but not statistically significant health care costs ($1993, p = 0.17), lower borderline significant odds of employment (OR = 0.41, 95% CIs [0.14, 1.20]), and significantly lower earnings ($19,374, p < 0.01). CONCLUSIONS: Treatment and prevention of ED may have broader economic benefits in terms of heath care savings and gains in work productivity than previously recognized. This exploratory study justifies large scale evaluations of the societal economic impact of eating disorders and comorbidities. PMID- 26844047 TI - Demographic and psychographic associations of consumer intentions to purchase healthier food products. AB - OBJECTIVE: This study investigated the associations of nutrition concerns, demographics, universalism (community oriented) values, perceived control over personal health and food buying, and perceived influence over the food system with intentions to purchase low fat, sugar and salt (LFSS) food products. METHODS: A national online survey of 2204 Australian consumers administered in November 2011. Structural equation modeling was used to examine associations of LFSS purchasing intentions with demographic, values, perceived control, and influence factors. RESULTS: Nutrition concern, perceived influence over the food system, and universalism values were key predictors of LFSS purchasing intentions. Almost two thirds (64.6%) of the variance associated with LFSS purchasing was explained by the structural equation model. CONCLUSION: Communication programs which focus on universalism values, nutrition concern and perceived influence over the food system are likely to increase LFSS purchasing and perhaps reduce the demand for energy dense, nutrient poor foods. PMID- 26844049 TI - Fresh produce consumption and the association between frequency of food shopping, car access, and distance to supermarkets. AB - BACKGROUND: Fresh fruit and vegetables are important components of a healthy diet. Distance to a supermarket has been associated with the ability to access fresh produce. METHODS: A randomly sampled telephone survey was conducted with the main shopper for 3000 households in New Orleans, Louisiana in 2011. Individuals were asked where and how often they shopped for groceries, frequency of consumption of a variety of foods, and whether they had access to a car. Bivariate models assessed the relationship between four outcomes: car access, distance to the store patronized by the respondent, number of monthly shopping trips, and daily servings of produce. Structural equation modeling (SEM) was used to distinguish direct and indirect effects. RESULTS: In bivariate models, car access was positively associated with number of shopping trips and produce consumption while distance was inversely associated with shopping trips. In SEM models, produce consumption was not associated with car access or distance, but to the number of monthly shopping trips. CONCLUSION: The frequency of shopping is associated with car access but a further distance deters it. Access to stores closer to the shopper may promote more frequent shopping and consumption of produce. PMID- 26844051 TI - Adult physical inactivity prevalence in the Muslim world: Analysis of 38 countries. AB - OBJECTIVE: Physical inactivity surveillance informs policy and treatment options toward meeting the World Health Organization's (WHO) goal of a 10% reduction in its prevalence by 2025. We currently do not know the aggregate prevalence for Muslim-majority countries, many of which have extremely high rates of comorbidities associated with physical inactivity. METHOD: Based on data for 163, 556 persons in 38 Muslim countries that were collected by the Global Physical Activity Questionnaire and the International Physical Activity Questionnaire, unweighted and weighted physical inactivity prevalence estimates were calculated. I used two-proportion Z tests to determine gender and ethnic differences within the sample and between the sample and 94 non-Muslim countries and odds ratios to determine the magnitude of significant differences. RESULTS: Total physical inactivity prevalence was 32.3% (95% CI: 31.9, 32.7). Prevalence among males and females was 28.8% and 35.5%, respectively. Prevalence among non-Arabs and Arabs was 28.6% and 43.7%, respectively. Females and Arabs were more likely physically inactive than their respective counterparts [OR = 1.36 (1.33, 1.39) and OR = 1.94 (1.90, 1.98)]. Muslim countries were more likely physically inactive [OR = 1.23 (1.22, 1.25)] than non-Muslim ones, which was primarily due to the influence of Arabs [OR = 2.01 (1.97, 2.04)], and in particular female Arabs [OR = 2.22 (2.17, 2.27)]. CONCLUSION: Physical inactivity prevalence in the Muslim world is higher than non-Muslim countries and the difference is primarily due to higher rates among Arabs. PMID- 26844050 TI - Medical marijuana programs - Why might they matter for public health and why should we better understand their impacts? AB - OBJECTIVE: Although cannabis is an illegal drug, 'medical marijuana programs' (MMPs) have proliferated (e.g., in Canada and several US states), allowing for legal cannabis use for therapeutic purposes. While both health risks and potential therapeutic benefits for cannabis use have been documented, potential public health impacts of MMPs - also vis-a-vis other psychoactive substance use - remain under-explored. METHODS: We briefly reviewed the emerging evidence on MMP participants' health status, and specifically other psychoactive substance use behaviors and outcomes. RESULTS: While data are limited in amount and quality, MMP participants report improvements in overall health status, and specifically reductions in levels of risky alcohol, prescription drug and - to some extent - tobacco or other illicit drug use; at the same time, increases in cannabis use and risk/problem patterns may occur. CONCLUSION: MMP participation may positively impact - for example, by way of possible 'substitution effects' from cannabis use - other psychoactive substance use and risk patterns at a scale relevant for public health, also influenced by the increasing population coverage of MMPs. Yet, net overall MMP-related population health effects need to be more rigorously and comprehensively assessed, including potential increases in cannabis use related risks and harms. PMID- 26844052 TI - Decreases in tanning behaviors following a short online survey: Potential for prevention? AB - OBJECTIVES: To date, tanning prevention programs have led to limited success. The aim of the present study was to investigate potential unexpected prevention effects of completing an online survey focused on tanning attitudes, behaviors, and knowledge among female college tanners. METHODS: A sample of 92 female undergraduate students from the USA, mean age = 20.09, SD = 1.41 years, who engaged in indoor tanning completed an online survey assessing awareness of tanning-related health risks, appearance-based motivations to tan and not to tan, media literacy related to tanning marketing, and tanning behaviors in 2013. Four months later, participants were invited to complete a follow-up survey assessing tanning intentions and behaviors since completing the initial survey. RESULTS: Fifty-one participants (55%) completed the follow-up questions, of whom 43 (84.3%) reported having decreased or ceased engaging in indoor tanning. In addition participants provided comments indicating that completing the survey had lead to decreases in their tanning behaviors. CONCLUSIONS: Our study presents novel and compelling support for using brief online surveys for decreasing health risk behaviors such as sunbed use. Such measures are extremely cost-effective and easy to disseminate and implement. Replication and extension of these findings are warranted. PMID- 26844053 TI - High school females and those with other vaccinations most likely to complete the Human Papillomavirus vaccine. AB - OBJECTIVE: Adolescent females' HPV vaccine completion in the U.S. is low. More recent research is needed to investigate factors that relate to HPV vaccine completion among female adolescents in the United States. METHODS: Provider validated data from the 2012 National Immunization Survey-Teen for females ages 13-17 years (N = 9058) were analyzed from February-May 2014 using survey sample weighted statistics. A multivariable Poisson regression estimated prevalence ratios (PR) for factors influencing HPV vaccine completion: mother's education, poverty status, adolescent's grade, facility type, and receipt of other adolescent vaccinations. RESULTS: In multivariable models, 9-12th grade daughters were more likely to complete HPV vaccination than 6-8th grade daughters (PR = 1.81, 95% CI = 1.58-2.06). Those seen in hospital facilities completed HPV vaccination 1.3 times more (PR = 1.29, 95% CI = 1.02-1.62) and those seen in private facilities were 1.2 times more likely to complete (PR = 1.22, 95% CI = 1.01-1.48), than those seen in public facilities, respectively. Compared to those without recommended adolescent vaccinations, receipt of seasonal influenza vaccination related to HPV vaccine completion (PR = 1.71, 95% CI = 1.54-1.89), as did receipt of TDAP vaccination (PR = 1.17, 95% CI = 1.03-1.33) and Meningitis vaccination (PR = 2.74, 95% CI = 2.20-3.42). CONCLUSIONS: Adolescent females in high school, seen in private/hospital facilities, and up to date on other recommended adolescent vaccinations are most likely to complete the HPV vaccine. PMID- 26844054 TI - Associations between rule-based parenting practices and child screen viewing: A cross-sectional study. AB - BACKGROUND: Child screen viewing (SV) is positively associated with poor health indicators. Interventions addressing rule-based parenting practices may offer an effective means of limiting SV. This study examined associations between rule based parenting practices (limit and collaborative rule setting) and SV in 6-8 year old children. METHODS: An online survey of 735 mothers in 2011 assessed: time that children spent engaged in SV activities; and the use of limit and collaborative rule setting. Logistic regression was used to examine the extent to which limit and collaborative rule setting were associated with SV behaviours. RESULTS: 'Always' setting limits was associated with more TV viewing, computer, smartphone and game-console use and a positive association was found between 'always' setting limits for game-console use and multi-SV (in girls). Associations were stronger in mothers of girls compared to mothers of boys. 'Sometimes' setting limits was associated with more TV viewing. There was no association between 'sometimes' setting limits and computer, game-console or smartphone use. There was a negative association between collaborative rule setting and game-console use in boys. CONCLUSIONS: Limit setting is associated with greater SV. Collaborative rule setting may be effective for managing boys' game-console use. More research is needed to understand rule-based parenting practices. PMID- 26844056 TI - Patient-physician communication regarding electronic cigarettes. AB - INTRODUCTION: Smokers are likely asking their physicians about the safety of e cigarettes and their potential role as a cessation tool; however, the research literature on this communication is scant. A pilot study of physicians in the United States was conducted to investigate physician-patient communication regarding e-cigarettes. METHODS: A total of 158 physicians were recruited from a direct marketing e-mail list and completed a short, web-based survey between January and April 2014. The survey addressed demographics, physician specialty, patient-provider e-cigarette communication, and attitudes towards tobacco harm reduction. RESULTS: Nearly two-thirds (65%) of physicians reported being asked about e-cigarettes by their patients, and almost a third (30%) reported that they have recommended e-cigarettes as a smoking cessation tool. Male physicians were significantly more likely to endorse a harm reduction approach. DISCUSSION: Physician communication about e-cigarettes may shape patients' perceptions about the products. More research is needed to explore the type of information that physicians share with their patients regarding e-cigarettes and harm reduction. PMID- 26844055 TI - Objectively measured and self-reported sedentary time in older Canadians. AB - OBJECTIVE: The aim of this study was to examine objectively measured total and self-reported leisure sedentary time among older Canadians by work status. METHODS: The analysis was based on 1729 older adults (60-79 years) from the 2007/09 and 2010/11 Canadian Health Measures Survey. Work status, functional limitations, smoking, and perceived health were assessed by self-report and waist circumference (WC) was measured. Total sedentary time (ST) and physical activity (PA) were objectively measured by accelerometer and leisure sedentary activities were assessed by questionnaire. RESULTS: 93.6% of individuals were sedentary for 8 or more hours per day. Measured ST did not differ by work status, while self reported leisure ST was higher in those not working compared to those working (239 vs. 207 minutes/day, p < 0.05). Correlates of measured ST were fair/poor perceived health (beta: 28.76, p < 0.01), smoking (beta: 17.12, p < 0.05), high risk WC (beta: 13.14, p < 0.05), and not meeting PA guidelines (beta: 35.67, p < 0.001). For self-reported leisure ST, working status (beta: 33.80, p < 0.001) and functional limitations (beta: 16.31, p < 0.05) were significant correlates. CONCLUSIONS: Older adults accumulate substantial ST regardless of their working status and ST is correlated with indicators of health risk. Older adults are an important target population for interventions to reduce ST. PMID- 26844057 TI - The relationship between children's physical activity and family income in rural settings: A cross-sectional study. AB - OBJECTIVE: To examine potential differences in children's physical activity and parent support of their children's physical activity based on family income within the rural setting. METHODS: A cross-sectional survey of 566 parents of children (5-15 years-old; mean = 7.7 years; standard deviation = 2.4) living in rural West Virginia from 2010 to 2011 was conducted. Children were recruited and had participated in a school-based health screening program. RESULTS: Overall, parents from a rural setting reported that their children engaged in an average of five days of physical activity for at least 60 min. Upon closer examination, children from lower-income families engaged in more physical activity, on average, than children from higher income families per parent report (mean = 6.6 days, confidence interval 95% = 4.9-6.0 vs. middle-income mean = 5.0, confidence interval 95% = 4.4-5.3 and highest-income mean = 4.5, confidence interval 95% = 4.1-4.7; p = .01). Rural parents supported their children's physical activity in numerous ways. Parents with the lowest incomes were more likely than parents from higher income families to encourage their children to be active and use their immediate environment for play and to be directly involved in physical activity with their children. More affluent parents were more likely to transport their children to other activity opportunities than parents from the lower income brackets. CONCLUSIONS: Lower income families may utilize their immediate environment and encourage activity among their children whereas more affluent families focus on organized opportunity more often than lower income families. These findings emphasize the need to conceptualize the role family income plays in physical activity patterns and the potential benefit it provides to some families. PMID- 26844059 TI - Are the correlates of sport participation similar to those of screen time? AB - OBJECTIVE: To explore longitudinal and cross-sectional correlates of sport participation and screen time in a nationally representative sample of Australian children. METHODS: The sample included 3956 child participants taken from the Longitudinal Study of Australian Children. Data were collected in 2004 (age range = 4-5 years) and 2012 (age range = 12-13 years) and included parental estimates of sport participation and total screen time (electronic gaming and television viewing) in addition to demographic, socioeconomic and environmental factors. RESULTS: Sport participation and total screen time were inversely correlated (r = - .10). Child demographics (sex, pubertal status, general health, and body mass index [BMI]), socioeconomic (neighborhood socioeconomic position, household income, parental education, and parental BMI) and environmental (neighborhood belonging, neighborhood safety, and neighborhood facilities) factors were related to both outcomes - in most cases a positive [negative] correlation with sport participation yielded a corresponding negative [positive] correlation with total screen time. CONCLUSION: Our findings show that demographic, socioeconomic and environmental factors measured at age 4 predict sport participation and screen time at age 12, and that the correlates of childhood sport participation and childhood sedentary behavior may be more similar than previously estimated. PMID- 26844058 TI - Nutrition knowledge, diet quality and hypertension in a working population. AB - OBJECTIVE: To examine if employees with higher nutrition knowledge have better diet quality and lower prevalence of hypertension. METHOD: Cross-sectional baseline data were obtained from the complex workplace dietary intervention trial, the Food Choice at Work Study. Participants included 828 randomly selected employees (18-64 years) recruited from four multinational manufacturing workplaces in Ireland, 2013. A validated questionnaire assessed nutrition knowledge. Food Frequency Questionnaires (FFQ) measured diet quality from which a DASH (Dietary Approaches to Stop Hypertension) score was constructed. Standardised digital blood pressure monitors measured hypertension. RESULTS: Nutrition knowledge was positively associated with diet quality after adjustment for age, gender, health status, lifestyle and socio-demographic characteristics. The odds of having a high DASH score (better diet quality) were 6 times higher in the highest nutrition knowledge group compared to the lowest group (OR = 5.8, 95% CI 3.5 to 9.6). Employees in the highest nutrition knowledge group were 60% less likely to be hypertensive compared to the lowest group (OR = 0.4, 95% CI 0.2 to 0.87). However, multivariate analyses were not consistent with a mediation effect of the DASH score on the association between nutrition knowledge and blood pressure. CONCLUSION: Higher nutrition knowledge is associated with better diet quality and lower blood pressure but the inter-relationships between these variables are complex. PMID- 26844060 TI - Failure to pay for social health insurance premiums: Acts of protest or desperation? AB - BACKGROUND: In Switzerland, basic health insurance is mandatory for all inhabitants, but a rising number of insured have arrears in premium payments, potentially leading to coverage suspension. We aimed at characterizing insured with debt enforcement proceedings with respect to socio-demographic and health utilization aspects. METHODS: Cross-sectional analysis of 508.000 insured with basic health insurance contracts in 2013, of whom 14,000 (2.8%) with debt enforcement proceedings, from 11 Swiss cantons. Groups were characterized using logistic regression and latent class analysis. RESULTS: Insured with debt enforcement proceedings were more likely to be young, male and without dependents (partner, kids). Having no supplementary insurance and receiving partial premium subsidies was associated with an increased debt enforcement proceedings risk. Within the debt enforcement proceedings group, three subgroups were identified: 60% were young and seemingly healthy, with a below-average fraction of premium subsidy recipients (18%) and low out-of-pocket payments in prior year (median Swiss Francs 0). Two groups consisted of relatively ill elderly persons (22%, 99% of whom with chronic illnesses) or families (18%), many of whom (29% and 51%) were recipients of premium subsidies. Median out-of-pocket payments in the prior year were high (Swiss Francs 625 and 688, respectively). CONCLUSIONS: Sixty percent of premium arrears derive from young insured without apparent financial problems; 40% are owed by elderly and families, which are potentially hurt by coverage loss. PMID- 26844061 TI - A feasibility study of a randomised controlled trial comparing fall prevention using exercise with or without the support of motivational interviewing. AB - OBJECTIVE: The aim of this investigation was to study the feasibility of a randomised controlled trial (RCT) based on a multicentre fall prevention intervention including exercise with or without motivational interviewing compared to standard care in community-living people 75 years and older. METHOD: The feasibility of a three-armed, randomised controlled trial was evaluated according to the following: process, resources, management by questionnaire, and treatment outcomes. The outcome measures were fall frequency, physical performance and falls self-efficacy evaluated after three months. Twelve physiotherapists conducted the measurements and treatments and responded to the questionnaire. The first 45 participants recruited to the ongoing RCT were included: 16 individuals in the Otago Exercise Program group (OEP), 16 individuals in the OEP combined with motivational interviewing group (MI), and 13 individuals in the control group. The study was conducted from November 2012 to December 2013. RESULTS: The feasibility of the study process, resources and management reached the set goals in most aspects; however, the set goal regarding the MI guide and planned exercise for the participating older people was not completely reached. No significant differences were found between the groups regarding the outcome measures. CONCLUSION: This study confirmed the acceptable feasibility for the study protocol in the ongoing RCT. PMID- 26844062 TI - Body image emotions, perceptions, and cognitions distinguish physically active and inactive smokers. AB - OBJECTIVES: To determine if body image emotions (body-related shame and guilt, weight-related stress), perceptions (self-perceived overweight), or cognitions (trying to change weight) differ between adolescents characterized by smoking and physical activity (PA) behavior. METHODS: Data for this cross-sectional analysis were collected in 2010-11 and were available for 1017 participants (mean (SD) age = 16.8 (0.5) years). Participants were categorized according to smoking and PA status into four groups: inactive smokers, inactive non-smokers, active smokers and active non-smokers. Associations between body image emotions, perceptions and cognitions, and group membership were estimated in multinomial logistic regression. RESULTS: Participants who reported body-related shame were less likely (OR (95% CI) = 0.52 (0.29-0.94)) to be in the active smoker group than the inactive smoker group; those who reported body-related guilt and those trying to gain weight were more likely (2.14 (1.32-3.48) and 2.49 (1.22-5.08), respectively) to be in the active smoker group than the inactive smoker group; those who were stressed about weight and those perceiving themselves as overweight were less likely to be in the active non-smoker group than the inactive smoker group (0.79 (0.64-0.97) and 0.41 (0.19-0.89), respectively). CONCLUSION: Body image emotions and cognitions differentiated the active smoker group from the other three groups. PMID- 26844063 TI - Predictive validity of the attitudes toward medical help-seeking scale. AB - OBJECTIVE: This study examines the predictive validity of the action/intention subscale of the attitudes toward seeking medical help scale in a college sample. PARTICIPANTS: Participants were 51 female undergraduates recruited from psychology classes. Data were collected at two time points between January and April, 2011. METHODS: Students completed the attitudes subscale and a measure of medical contacts twice, over a two month interval. RESULTS: Internal consistency and test-retest reliability of the measure were supported. Correlations between time one attitudes and medical contacts/intentions at time two provide evidence for predictive validity of the measure. CONCLUSION: This relatively brief, psychometrically sound measure of attitudes toward medical help seeking can be used to identify individuals who may be reluctant to seek health care and to assess the effectiveness of health education programs. PMID- 26844064 TI - Prevalence and correlates of cell phone use among Texas drivers. AB - INTRODUCTION: Cell phone use while driving restricts peripheral awareness and impairs reaction time. This study assessed the 3-year prevalence of cell phone use (CPU) of drivers and characteristics associated with its use in six cities across Texas, 2011-2013. METHODS: CPU and driver characteristics were observed among motor vehicles (n = 1280) stopped at major intersections in medical and academic campuses. A multivariable logistic regression model described the association between driver characteristics and CPU. RESULTS: The overall prevalence of any CPU was 18.7%. Any type of CPU and talking tended to decline, while texting seemed to increase from 2011 to 2013. CPU was more likely among female drivers (OR = 1.63; 95% CI = 1.21, 2.20), drivers < 25 years of age (OR = 4.12; 95% CI = 2.29, 7.39), and drivers without passengers (OR = 4.40; 95% CI = 2.82, 6.88). CONCLUSION: Despite its dangers, CPU remains popular among Texas drivers. CPU and texting bans should target public health campaigns towards female and younger drivers. PMID- 26844065 TI - The role of health literacy and communication habits on previous colorectal cancer screening among low-income and uninsured patients. AB - OBJECTIVE: To determine the association between health literacy, communication habits and colorectal cancer (CRC) screening among low-income patients. METHODS: Survey responses of patients who received financial assistance for colonoscopy between 2011 and 2014 at a family medicine residency clinic were analyzed using multivariate logistic regression (n = 456). There were two dependent variables: (1) previous CRC screening and (2) CRC screening adherence. Our independent variables of interest were health literacy and communication habits. RESULTS: Over two-thirds (67.13%) of respondents had not been previously screened for CRC. Multivariate analysis showed a decreased likelihood of previous CRC screening among those who had marginal (OR = 0.52; 95% CI = 0.29-0.92) or inadequate health literacy (OR = 0.49; 95% CI = 0.27-0.87) compared to those with adequate health literacy. Controlling for health literacy, the significant association between educational attainment and previous CRC screening was eliminated. Thus, health literacy mediated the relationship between educational attainment and previous CRC screening. There was no significant association between communication habits and previous CRC screening. There was no significant association between screening guideline adherence, and health literacy or communication. CONCLUSION: Limited health literacy is a potential barrier to CRC screening. Suboptimal CRC screening rates reported among those with lower educational attainment may be mediated by limited health literacy. PMID- 26844066 TI - Examining food purchasing patterns from sales data at a full-service grocery store intervention in a former food desert. AB - BACKGROUND: The Good Food Junction Grocery Store was opened in a former food desert in the inner city of Saskatoon, Canada. OBJECTIVE: The purpose of this research was to examine, using grocery store sales data, healthy and less healthful food purchasing over a one-year period beginning eight months after opening by shoppers' neighborhood of residence. DESIGN: A multilevel cross sectional design was used. The sample consisted of members of the Good Food Junction with a valid address in Saskatoon, Saskatchewan. All purchases made by members who reported their postal code of residence from May 15, 2013 to April 30, 2014 were analyzed. The outcome variable was the total amount spent on foods in 11 food groups. Linear random intercept models with three levels were fit to the data. RESULTS: Shoppers who were residents of former food desert neighborhoods spent $0.7 (95% CI: 0.2 to 1.2) more on vegetables, and $1.2 (95% CI: - 1.8 to - 0.6) less on meat, and $1.1 (95% CI: - 2.0 to - 0.3) less on prepared foods than shoppers who did not reside in those neighborhoods. CONCLUSIONS: When given geographical access to healthy food, people living in disadvantaged former food desert neighborhoods will take advantage of that access. PMID- 26844067 TI - Differences in adolescents' physical activity from school-travel between urban and suburban neighbourhoods in Metro Vancouver, Canada. AB - OBJECTIVE: To investigate differences in moderate-to-vigorous physical activity (MVPA) from school-travel between adolescents in urban and suburban neighbourhoods and to describe its relative contribution to MVPA on school days. METHODS: We measured 243 adolescents (51% male, grades 8-10) from Vancouver's walkable downtown core and its largely car-dependent suburb Surrey (fall 2011, 2013). We estimated mean school-travel MVPA from accelerometry (hour before/after school on >= 2 days; n = 110, 39% male) and compared school-travel MVPA by neighbourhood type and school-travel mode. The influence of mean school-travel MVPA on mean school-day MVPA (>= 600 min valid wear time on >= 2 days) was examined by linear regression. RESULTS: Over half of students used active modes (urban: 63%, suburban: 53%). Those using active travel and living in the urban neighbourhood obtained the most school-travel MVPA (22.3 +/- 8.0 min). Urban passive travellers used public transit and obtained more school-travel MVPA than suburban students (16.9 +/- 6.2 vs. 8.0 +/- 5.3, p < 0.001), who were primarily driven. Regardless of mode or neighbourhood type, over one-third of school-day MVPA was explained by school-travel MVPA (R (2) = 0.38, p < 0.001). CONCLUSION: Urban dwelling may facilitate greater school-travel MVPA in adolescents. School travel MVPA is an important contributor to adolescents' school-day MVPA. Where feasible, physically active options for school-travel should be promoted, including public transit. PMID- 26844068 TI - A comparison of adolescent smoking initiation measures on predicting future smoking behavior. AB - OBJECTIVES: Evidence suggests that age at smoking initiation has implications for tobacco use, nicotine dependence, and resulting long-term health and chronic disease outcomes. The objective of the current study was to examine two different measures of smoking onset and to compare their validity in predicting future adolescent smoking survey. METHODS: Data from grades 9-12 students who participated in the 2012/2013 Youth Smoking Survey, a nationally-generalizable Canadian survey, and who had ever tried a cigarette, even a few puffs (n = 8126) were used in a multivariable logistic regression analysis to examine the association between age at smoking onset and current smoking behavior. RESULTS: Both "age at first puff" and "age at first whole cigarette" were significantly associated with current smoking status. Specifically, a delay of one year in the age at first puff was associated with lower odds of being a current smoker by 24% (AOR = 0.76, 95% CI = 0.73-0.79). Similarly, high school students who smoked their first whole cigarette at old age were less likely to report being a current smoker (AOR = 0.66, 95% CI = 0.62-0.71). CONCLUSION: Efforts to prevent smoking uptake among youth, especially younger youth, are especially important in tobacco control efforts. PMID- 26844069 TI - Maintenance of physical activity: Do we know what we are talking about? AB - OBJECTIVE: Physical activity has to be performed regularly in order to achieve long-term health benefits. Studying the maintenance of physical activity and comparing study results requires a shared descriptive definition and a derived operationalization. Both are still lacking. The goal of this article is to briefly summarize how "maintenance of physical activity" is used in the scientific literature. Further, a descriptive definition and its operational application are introduced. METHOD: A rapid literature search was completed in order to summarize the different concepts and usages of the term "maintenance of physical activity." RESULTS: "Maintenance of physical activity" is used and defined in different ways. All of them have strengths and weaknesses. An approach that respects the volatility of physical activity is lacking. That's why the lapse-recovery relationship is introduced. CONCLUSION: People's physical activity volume is often volatile, which is crucial for defining and assessing "maintenance of physical activity". The lapse-recovery relationship is an individual-centered approach respecting this volatility. It refers to an intentionally changed behavior and uses lapses and recoveries as indicators to operationalize the maintenance of physical activity. PMID- 26844070 TI - Assessing effective smoking cessation intervention in primary care. PMID- 26844071 TI - Impact of travel mode shift and trip distance on active and non-active transportation in the Sao Paulo Metropolitan Area in Brazil. AB - BACKGROUND: Changes in urban mobility play a major role in transforming metropolitan areas into healthier places. This study quantified the impact of changes in travel mode shift and trip distance on active and non-active transportation of working age adult population of Sao Paulo. METHODS AND FINDINGS: Through different scenarios, we estimated the daily time spent in transportation per inhabitant (divided in active and non-active transportation time) and the proportion of inhabitants accumulating 30 min or more of daily active transportation. The replacement of individual for collective motorized modes in long distance trips (> 1000 m) in combination with the substitution of long for short trips positively impacted all outcomes. Compared to the current situation, there was an increase in the active transportation time (from 19.4 to 26.7 min/inhabitant), which also increased the proportion of adults active for transportation (from 27.6% to 35.4%). Additionally, the non-active transportation time decreased (from 67.0 to 26.2 min/inhabitant), which helped to reduce the total time spent in transportation (from 86.4 to 52.9 min/inhabitant). CONCLUSION: Transport and urban planning policies to reduce individual motorized trips and the number of long trips might produce important health benefits, both by increasing population levels of active transportation and reducing the non active and the total time of daily trips. PMID- 26844072 TI - Cost-effectiveness of retreatment with varenicline after failure with or relapse after initial treatment for smoking cessation. AB - OBJECTIVES: A recent trial showed the clinical benefit of retreatment with varenicline in subjects failing on the initial treatment, or relapsing after initial success. The objective of this study was to evaluate the cost effectiveness of retreatment with varenicline compared with other smoking cessation interventions. METHODS: A published Markov model was adapted to compare one quit attempt of varenicline followed by retreatment to treatment/retreatment with nicotine replacement therapy (NRT), bupropion or placebo, and with only 1 quit attempt of varenicline. Efficacy was obtained from clinical trials. Incidence of smoking-related diseases was based on published data. Cost of therapies and complications was obtained from databases and literature. RESULTS: For 1000 smokers willing to quit, varenicline retreatment saves 275,000?, 118,000?, 316,000? and 237,000? compared to NRT, bupropion, placebo, or one single varenicline quit attempt respectively at lifetime and from the healthcare payer perspective. The number of quality adjusted life years gained is 74, 63, 193 and 111 respectively. Sensitivity analyses showed the robustness of these findings. CONCLUSION: This analysis suggests that in the long term, varenicline retreatment is a dominant intervention, meaning both greater health gains and greater costs saved, over other possible interventions and therefore should be considered as a standard option. PMID- 26844073 TI - Nicotine replacement therapy to aid gradual cessation in smokers with no intention to quit: Association between reduction quantity and later abstinence. AB - OBJECTIVE: We examined how quantity and trajectory of smoking reduction influence later abstinence in smokers without intention to quit and being prescribed free nicotine replacement therapy (NRT). METHOD: We conducted an a posteriori analysis from a data archive of adult smokers in a randomized controlled trial of smoking reduction using counseling and free NRT (n = 928). Reduction was analyzed as the absolute and percentage decrease in self-reported daily cigarette consumption at three follow-ups (1 week, 1 and 3 months) compared with the baseline. Logistic regression model and multiple imputation were used to examine the association between early reduction and abstinence at 6 months. RESULTS: Reducing 10% of cigarette consumption at the three follow-ups was associated with 16% (95% CI 5 28%), 23% (95%CI 11-36%) and 27% (95% CI 13-42%) increase in abstinence, respectively. Greater reduction predicted abstinence when the percentage reduction was more than one-third (above 31.4%). Progressive increase in the percentage reduction predicted more abstinence (OR = 1.90, 95%CI 1.01-3.58). CONCLUSIONS: Greater percentage reduction by at least one-third and progressive reduction predicted abstinence in those who reduced smoking. Such new evidence can guide the improvement of clinical service for tobacco dependency treatment and support further studies on smoking reduction and cessation. PMID- 26844074 TI - A self-regulation resource model of self-compassion and health behavior intentions in emerging adults. AB - OBJECTIVE: This study tested a self-regulation resource model (SRRM) of self compassion and health-promoting behavior intentions in emerging adults. The SRRM posits that positive and negative affect in conjunction with health self-efficacy serve as valuable self-regulation resources to promote health behaviors. METHODS: An online survey was completed by 403 emerging adults recruited from the community and a Canadian University in late 2008. Multiple meditation analyses with bootstrapping controlling for demographics and current health behaviors tested the proposed explanatory role of the self-regulation resource variables (affect and self-efficacy) in linking self-compassion to health behavior intentions. RESULTS: Self-compassion was positively associated with intentions to engage in health-promoting behaviors. The multiple mediation model explained 23% of the variance in health behavior intentions, with significant indirect effects through health self-efficacy and low negative affect. CONCLUSION: Interventions aimed at increasing self-compassion in emerging adults may help promote positive health behaviors, perhaps through increasing self-regulation resources. PMID- 26844075 TI - Adherence to the Mediterranean diet among employees in South West England: Formative research to inform a web-based, work-place nutrition intervention. AB - OBJECTIVE: The aim of this study is to assess internet usage patterns and adherence to the Mediterranean diet among employees in South West England, UK and their differences by personal characteristics. METHOD: A cross-sectional survey was conducted in 2014 among 590 adults (428 women, 162 men, mean age 43.8 years), employees of four work-place settings. Mediterranean diet adherence was assessed using a validated food frequency questionnaire. Adherence differences were assessed by gender, marital status, education, number of children and food shopping and preparation responsibility. RESULTS: On average, participants reported moderate adherence to the Mediterranean diet. Higher adherence was reported for alcohol, vegetables, cereals and fruit. Few participants achieved high adherence to the Mediterranean diet recommendations for legumes (5.3%), fish (3.2%), dairy products (4.8%), red meat (11.9%), poultry (11.1%) and olive oil (18.2%). A higher Mediterranean diet score was reported among participants who were married/cohabiting, those with higher education attainment and shared responsibility for food preparation. CONCLUSION: Improvement in the consumption of several Mediterranean diet components is needed to increase adherence in this sample of adults. The findings have the potential to inform the development of a web-based intervention that will focus on these foods to promote the Mediterranean diet in work-place settings in South West England. PMID- 26844076 TI - Weight gain in freshman college students and perceived health. AB - BACKGROUND: We determined body weight increase in first year Dutch college students. We had the objective to determine whether the awareness of the unhealthy lifestyle raised concerns and willingness to change habits. METHODS: Body weight, heartbeat, BMI, body fat percentages, and blood pressure values were collected from 1095 students. Comprehensive statistical analysis was performed on the data. RESULTS: The students had a mean weight gain of 1.1 kg and an average BMI gain of 0.35. Members of a student corps gained significantly more weight (1.6 +/- 3.1 kg) than non-members (1.0 +/- 2.5 kg), while students who are living independently gained an average of 0.5 kg more than students living with their parents (p < 0.05). Approximately 40% of the students changed their eating patterns and 30.7% of the students consumed more alcohol. CONCLUSIONS: Students experienced hindrance in physical exercise and mental well-being. Students with a high BMI without irregular eating habits were willing to change their lifestyle. However, students who had irregular lifestyles exhibited the lowest willingness to change their eating behaviors and to lose weight. Our study provides insight into means by which adolescents at high risk for weight gain can be approached to improve experienced quality of life. PMID- 26844077 TI - Mobility disability and the pattern of accelerometer-derived sedentary and physical activity behaviors in people with multiple sclerosis. AB - OBJECTIVE: Low physical activity and high sedentary behavior levels are major concerns in persons with multiple sclerosis (MS) and these differ depending on the level of mobility disability. However, the manner in which daily activity is accumulated is currently unknown in this population. METHODS: A secondary analysis was performed on a combined data set of persons with MS from two previous investigations of physical activity and symptomatic or quality of life outcomes in the United States over a two year period (2007-2009). Mobility disability status was determined using the Patient Determined Disease Steps (PDDS) while activity behavior was objectively monitored using an ActiGraph accelerometer for 7 days. RESULTS: Persons with MS who have mobility disability were involved in sedentary behavior, light and moderate intensity activity for 65%, 34% and 1% of the day, respectively compared to 60%, 37%, and 3%, respectively in those without mobility disability (p < 0.05). Breaks in sedentary time did not differ by mobility disability status. Compared to those without mobility disability, the average number of sedentary bouts longer than 30 min was greater in those with mobility disability (p = 0.016). CONCLUSION: Persons with MS with mobility disability are less active, engage in more sedentary behavior and accumulate prolonged sedentary bouts. PMID- 26844078 TI - Relationships between sitting time and health indicators, costs, and utilization in older adults. AB - OBJECTIVE: To examine whether self-reported sitting time is related to various health indicators, health costs, and utilization in adults over age 65. METHODS: A retrospective cross-sectional cohort study was conducted using the electronic health record (EHR) from an integrated health system in Washington State. Members who completed an online health risk assessment (HRA) between 2009 and 2011 (N = 3538) were eligible. The HRA assessed sitting time, physical activity, and health status. Diagnosis codes for diabetes and cardiovascular disease (CVD), height and weight for body mass index (BMI) calculations, health care utilization and health costs were extracted from the EHR. Linear regression models with robust standard errors tested differences in sitting time by health status, BMI category, diabetes and CVD, health costs, and utilization adjusting for demographic variables, BMI, physical activity, and health conditions. RESULTS: People classified as overweight and obese, that had diabetes or CVD, and with poorer self-rated health had significantly higher sitting time (p < .05). Total annual adjusted health care costs were $126 higher for each additional hour of sitting (p < .05; not significant in final models including health conditions). CONCLUSION: Sitting time may be an important independent health indicator among older adults. PMID- 26844079 TI - An educational strategy for improving knowledge about breast and cervical cancer prevention among Mexican middle school students. AB - INTRODUCTION: Prevention programs have not achieved the expected results in preventing mortality from breast and cervical cancer in Mexico. Therefore, we propose a complementary strategy. METHODOLOGY: An educational strategy for high school students in Mexico (2011-2013) was designed (longitudinal design, two measurements and a single intervention). The postintervention assessment included: 1) knowledge acquired by students about cancer prevention and 2) The performance of the student as a health promoter in their household. The strategy was based on analysis of cases and developed in three sessions. An assessment tool was designed and validated (Test-Retest). The levels of knowledge according to the qualifications expected by chance were determined. Wilcoxon test compared results before and after intervention. RESULTS: An assessment instrument with 0.80 reliability was obtained. 831 high school students were analyzed. Wilcoxon rank-sum test showed a significant learning after the intervention (Z = - 2.64, p = 0.008) with improvement of levels of knowledge in a 154.5%. 49% of students had a good performance as health promoters. CONCLUSIONS: The learning in preventive measures is important to sensitize individuals to prevention campaigns against cancer. This strategy proved to improve the level of knowledge of students in an easy and affordable way. PMID- 26844080 TI - The remarkable decrease in cigarette smoking by American youth: Further evidence. AB - OBJECTIVE: To examine decreases over time in cigarette smoking prevalence and intensity among American students in 8th, 10th, and 12th grades. METHODS: Data from Monitoring the Future on students' smoking, across four measures of differing intensity of smoking, are compared over time and across grade levels. Data are available since 1975 for 12th graders and since 1991 for 8th and 10th graders. RESULTS: For all three grade levels, all four measures decreased substantially. The decreases became larger as the measures moved from least to most intensive (respectively, lifetime (ever) smoking and >= 1/2 pack of cigarettes per day). Decreases exceeded three-quarters for every grade for the two most intensive measures of smoking: daily smoking and >= 1/2 pack per day. For every measure, 8th graders' percentage decreases were the largest and 12th graders' the smallest. 12th graders' absolute (percentage-point) decreases were the largest for every measure. CONCLUSION: Cigarette smoking, the most dangerous form of tobacco use, has decreased dramatically among American students. The fact that decreases are larger for more intensive measures of smoking indicates that simply tracking 30-day prevalence, often labeled "current smoking," significantly understates the decrease in youth smoking over time. PMID- 26844081 TI - Knowledge and risk perceptions of the Ebola virus in the United States. AB - OBJECTIVES: The Ebola epidemic has received extensive media coverage since the first diagnosed cases of the virus in the US. We investigated risk perceptions of Ebola among individuals living in the US and measured their knowledge of the virus. METHOD: US residents completed an online survey (conducted 14-18 November 2014) that assessed their Ebola knowledge and risk perceptions. RESULTS: Respondents who were more knowledgeable of Ebola perceived less risk of contracting the virus and were less worried about the virus, but also regarded Ebola as more serious than less knowledgeable respondents. The internet served as a major source of additional information among knowledgeable respondents. CONCLUSION: The findings suggest that the provision of health information about Ebola may be effective in informing the public about Ebola risks and of preventive measures without curtailing the seriousness of the virus. Policymakers may seek to further exploit the internet as a means of delivering information about Ebola in the US and worldwide. PMID- 26844082 TI - Screen time is associated with dietary intake in overweight Canadian children. AB - OBJECTIVES: To describe the relationship between screen time and dietary intake among children, and to examine this association in relation to body weight. METHODS: A cross-sectional analysis of 630 Canadian children aged 8-10 years with at least one obese biological parent. Measurements included body mass index (BMI), screen time (television, video game, computer), physical activity (accelerometer over 7 days), and diet (three 24-hour recalls for the calculation of the Canadian Healthy Eating Index (HEI-C)). Multivariate linear regression models were used to describe the relationship between screen time (>= 2 h/d vs. < 2 h/d) and intake of nutrients and foods among healthy weight and overweight/obese children. RESULTS: The overall median [interquartile range] daily screen time was 2.2 [2.4] hours and 43% of children had a BMI of >= 85th percentile. Longer screen time above the recommendation (>= 2 h/d) was associated with higher intake of energy (74 kcal, SE = 35), lower intake of fiber (- 0.6 g/1000 kcal, SE = 0.2) and vegetables & fruit (- 0.3 serving/1000 kcal, SE = 0.1) among all participants and with higher estimates in the overweight subgroup. An overall lower HEI-C (- 1.6, SE = 0.8) was also observed among children with screen time of >= 2 h/d. Among children of < 85th BMI percentile, longer screen time was associated with lower intake of vegetables & fruit (- 0.3 serving/1000 kcal, SE = 0.1) only. CONCLUSION: Screen time is associated with less desirable food choices, particularly in overweight children. PMID- 26844083 TI - Predicting intentions and behaviours in populations with or at-risk of diabetes: A systematic review. AB - PURPOSE: To systematically review the Theory of Planned Behaviour studies predicting self-care intentions and behaviours in populations with and at-risk of diabetes. METHODS: A systematic review using six electronic databases was conducted in 2013. A standardised protocol was used for appraisal. Studies eligibility included a measure of behaviour for healthy eating, physical activity, glucose monitoring, medication use (ii) the TPB variables (iii) the TPB tested in populations with diabetes or at-risk. RESULTS: Sixteen studies were appraised for testing the utility of the TPB. Studies included cross-sectional (n = 7); prospective (n = 5) and randomised control trials (n = 4). Intention (18% 76%) was the most predictive construct for all behaviours. Explained variance for intentions was similar across cross-sectional (28-76%); prospective (28-73%); and RCT studies (18-63%). RCTs (18-43%) provided slightly stronger evidence for predicting behaviour. CONCLUSIONS: Few studies tested predictability of the TPB in populations with or at-risk of diabetes. This review highlighted differences in the predictive utility of the TPB suggesting that the model is behaviour and population specific. Findings on key determinants of specific behaviours contribute to a better understanding of mechanisms of behaviour change and are useful in designing targeted behavioural interventions for different diabetes populations. PMID- 26844084 TI - Shopper marketing nutrition interventions: Social norms on grocery carts increase produce spending without increasing shopper budgets. AB - OBJECTIVES: We assessed the efficacy of an easy-to-implement shopper marketing nutrition intervention in a pilot and two additional studies to increase produce demand without decreasing store profitability or increasing shopper budgets. METHODS: We created grocery cart placards that detailed the number of produce items purchased (i.e., descriptive norm) at particular stores (i.e., provincial norm). The effect of these placards on produce spending was assessed across 971,706 individual person grocery store transactions aggregated by day. The pilot study designated a baseline period (in both control and intervention store) followed by installation of grocery cart placards (in the intervention store) for two weeks. The pilot study was conducted in Texas in 2012. In two additional stores, we designated baseline periods followed by 28 days of the same grocery cart placard intervention as in the pilot. Additional interventions were conducted in New Mexico in 2013. RESULTS: The pilot study resulted in a significant difference between average produce spending per day per person across treatment periods (i.e., intervention versus same time period in control) (16%) and the difference between average produce spending per day per person across stores in the control periods (4%); Furthermore, the same intervention in two additional stores resulted in significant produce spending increases of 12.4% and 7.5% per day per person respectively. In all stores, total spending did not change. CONCLUSIONS: Descriptive and provincial social norm messages (i.e., on grocery cart placards) may be an overlooked tool to increase produce demand without decreasing store profitability and increasing shopper budgets. PMID- 26844086 TI - Intensive lifestyle intervention including high-intensity interval training program improves insulin resistance and fasting plasma glucose in obese patients. AB - OBJECTIVES: To analyze the effects of a long-term intensive lifestyle intervention including high-intensity interval training (HIIT) and Mediterranean diet (MedD) counseling on glycemic control parameters, insulin resistance and beta-cell function in obese subjects. METHODS: The glycemic control parameters (fasting plasma glucose, glycated hemoglobin), insulin resistance, and beta-cell function of 72 obese subjects (54 women; mean age = 53 +/- 9 years) were assessed at baseline and upon completion of a 9-month intensive lifestyle intervention program conducted at the cardiovascular prevention and rehabilitation center of the Montreal Heart Institute, from 2009 to 2012. The program included 2-3 weekly supervised exercise training sessions (HIIT and resistance exercise), combined to MedD counseling. RESULTS: Fasting plasma glucose (FPG) (mmol/L) (before: 5.5 +/- 0.9; after: 5.2 +/- 0.6; P < 0.0001), fasting insulin (pmol/L) (before: 98 +/- 57; after: 82 +/- 43; P = 0.003), and insulin resistance, as assessed by the HOMA IR score (before: 3.6 +/- 2.5; after: 2.8 +/- 1.6; P = 0.0008) significantly improved, but not HbA1c (%) (before: 5.72 +/- 0.55; after: 5.69 +/- 0.39; P = 0.448), nor beta-cell function (HOMA-beta, %) (before: 149 +/- 78; after: 144 +/- 75; P = 0.58). CONCLUSION: Following a 9-month intensive lifestyle intervention combining HIIT and MedD counseling, obese subjects experienced significant improvements of FPG and insulin resistance. This is the first study to expose the effects of a long-term program combining HIIT and MedD on glycemic control parameters among obese subjects. PMID- 26844085 TI - Prediction of bone mineral density and content from measures of physical activity and sedentary behavior in younger and older females. AB - BACKGROUND: Little is known regarding the extent to which physical activity (PA) and sedentary behavior (SB) influence bone mineral content (BMC) and bone mineral density (BMD) in females across the lifespan. METHODS: Data from 2232 females aged 12 years and older collected as part of the 2007-2008 National Health and Nutrition Examination Survey were analyzed. Categories of PA and SB were used to predict femoral and spinal BMD and BMC in four age groups (G1: 12-17; G2: 18-39; G3: 40-64; G4: >= 65 years). Self-reported PA categories included sufficient moderate-to-vigorous recreational PA (S-MVRPA) and insufficient MVRPA (I-MVRPA). RESULTS: G1 females who accumulated S-MVRPA displayed greater femoral and spinal BMC and BMD compared to G1 females who displayed I-MVRPA. For G4 females, higher levels of SB were associated with lower femoral BMC and BMD. CONCLUSIONS: These findings highlight the importance of engaging in sufficient moderate-to-vigorous physical activity during adolescence and reducing sedentary behavior in older adults to improve bone health in females. PMID- 26844087 TI - Derivation of indices of socioeconomic status for health services research in Asia. AB - BACKGROUND: Environmental contexts have been shown to predict health behaviours and outcomes either directly or via interaction with individual risk factors. In this paper, we created indexes of socioeconomic disadvantage (SEDI) and socioeconomic advantage (SAI) in Singapore to test the applicability of these concepts in an Asian context. These indices can be used for health service resource allocation, research and advocacy. METHODS: We used principal component analysis (PCA) to create SEDI and SAI using a structured and iterative process to identify and include influential variables in the final index. Data at the master plan geographical level was obtained from the most recent Singapore census 2010. RESULTS: The 3 areas with highest SEDI scores were Outram (120.1), followed by Rochor (111.0) and Downtown Core (110.4). The areas with highest SAI scores were Tanglin, River Valley and Newton. The SAI had 89.6% of variation explained by the final model, as compared to 67.1% for SEDI, and we recommend using both indices in any analysis. CONCLUSION: These indices may prove useful for policy-makers to identify spatially varying risk factors, and in turn help identify geographically targeted intervention programs, which can be more cost effective to conduct. PMID- 26844088 TI - Pregnant women's attitudes toward influenza vaccination while breastfeeding. AB - OBJECTIVE: The goal of this study was to assess the concerns pregnant women have about influenza vaccination while breastfeeding and to determine if having these concerns represents a barrier to vaccination uptake. METHODS: The Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) conducted a prospective cohort study in the US and Canada of influenza vaccine safety among pregnant women, oversampling vaccinated women. Data for the present paper are from an additional cross-sectional telephone survey completed during the 2010-2011 and 2012-2013 influenza seasons. RESULTS: We surveyed 431 pregnant women about their attitudes regarding influenza vaccination while breastfeeding. Almost half of the participants identified one or two concerns and 4% reported three or more concerns. About one quarter reported that they would be unlikely to have an influenza vaccination while breastfeeding. In the multivariate model, those reporting 1-2 concerns (OR = 0.16, 95% CI 0.09-0.28) and those reported 3 or more concerns (OR = 0.07, 95% CI 0.02-0.22) had lower odds of being likely to vaccinate. CONCLUSIONS: Pregnant women and postpartum women who are breastfeeding could benefit from receiving information and recommendations specific to vaccination from their healthcare providers, with a focus on discussing known risks and benefits to the baby's health. PMID- 26844089 TI - Neighbourhood environments and obesity among adults: A multilevel analysis of an urban Brazilian context. AB - Objective. This study identified environmental variables associated with obesity in the adult population of a city in Brazil. Methods. It was conducted using the Surveillance System for Risk and Protective Factors for Chronic Diseases by Telephone Survey from 2008 to 2010. The body mass index (BMI) was calculated from the participants' self-reported weight and height. Obesity was defined as a BMI >= 30 kg/m2. The food establishments, georeferenced areas conducive to physical activity, total income of the neighbourhood, homicide rate and population density were used to characterise the environment. In addition, individual variables were considered. A multilevel logistic regression was performed. Results. A total of 5273 individuals were evaluated. The odds of obesity was found to be significantly decreased with increases in the number of establishments that sell healthy food, number of restaurants, number of places for physical activity and total income - in different models. In addition, these associations remained significant after adjustment for age, gender, education and consumption of meat with visible fat. Conclusions. This study contributes to a better understanding of the complex interaction between environmental and individual determinants of obesity and may aid in the development of effective interventions, such as the expansion of obesity control programmes. PMID- 26844090 TI - Radon potential, geologic formations, and lung cancer risk. AB - OBJECTIVE: Exposure to radon is associated with approximately 10% of U.S. lung cancer cases. Geologic rock units have varying concentrations of uranium, producing fluctuating amounts of radon. This exploratory study examined the spatial and statistical associations between radon values and geological formations to illustrate potential population-level lung cancer risk from radon exposure. METHOD: This was a secondary data analysis of observed radon values collected in 1987 from homes (N = 309) in Kentucky and geologic rock formation data from the Kentucky Geological Survey. Radon value locations were plotted on digital geologic maps using ArcGIS and linked to specific geologic map units. Each map unit represented a package of different types of rock (e.g., limestone and/or shale). Log-transformed radon values and geologic formation categories were compared using one-way analysis of variance. RESULTS: Observed radon levels varied significantly by geologic formation category. Of the 14 geologic formation categories in north central Kentucky, four were associated with median radon levels, ranging from 8.10 to 2.75 pCi/L. CONCLUSION: Radon potential maps that account for geologic factors and observed radon values may be superior to using observed radon values only. Knowing radon-prone areas could help target population-based lung cancer prevention interventions given the inequities that exist related to radon. PMID- 26844091 TI - Assessing implementation of evidence-based childhood obesity prevention strategies in schools. AB - OBJECTIVE: Research suggests that schools can play a key role in obesity prevention by implementing evidence-based strategies promoting student health. This study explores school climate factors underlying implementation of evidence based health and wellness policies and practices in Kindergarten-8th grade programs in the Southwestern United States. METHOD: Utilizing a participatory research survey approach conducted in December 2011 with school health professionals (N = 62) and a multiple regression design, a moderated predictive model of implementation climate (i.e., attitudes and beliefs about prevention, school commitment to prevention, barriers, and stakeholder collaboration) was tested. RESULTS: Barriers to obesity prevention efforts, such as lack of resources, support, or strategy clarity, hinder implementation of healthy food policies despite strong school commitment to prevention. Along with the commitment to prevention, stakeholder collaboration predicts physical education strategies, specifically reducing restricted access to physical education as a punishment for student misconduct. CONCLUSION: Obesity prevention strategy implementation relies on the supportiveness and structure of school climates. Barriers to prevention can impede efforts despite school commitment toward prevention, while stakeholder collaboration can enhance the likelihood that practices are in place. PMID- 26844092 TI - Determinants of healthcare provider recommendations for influenza vaccinations. AB - OBJECTIVE: Investigate determinants of receiving healthcare provider (HCP) recommendations for seasonal and H1N1 influenza vaccinations. METHODS: Using a United States national sample of adults 18 + from the National 2009 H1N1 Flu Survey, multivariate regression models estimated the likelihood of receiving a HCP recommendation. Covariates included demographics, socioeconomic status, and Advisory Committee on Immunization Practices (ACIP) priority groups. RESULTS: Adults age 55-64 and 65 + were more likely to report a HCP recommendation when compared to adults age 18-34 (OR: 1.483, 95%CI: 1.237-1.778 and OR: 1.738, 95%CI: 1.427-2.116, respectively). Chronically ill adults had 58.0% (95%CI: 1.414-1.765) higher odds of receiving a HCP recommendation than non-chronically ill adults. Patients visiting a doctor once and twice had 28.7% (95%CI: 0.618-0.821) and 17.1% (95%CI: 0.721-0.952) lower odds of receiving a HCP recommendation when compared to adults visiting their doctor at least four times. And, compared to Non-Hispanic Whites, Non-Hispanic Blacks had 28.4% (95%CI: 1.064-1.549) higher odds of receiving a recommendation. CONCLUSIONS: ACIP priority groups experienced higher rates of recommendations compared to non-ACIP groups. Racial differences in HCP recommendations cannot explain racial disparities in flu vaccination rates. PMID- 26844094 TI - Preventable hospitalizations among adult Medicaid beneficiaries with concurrent substance use disorders. AB - OBJECTIVE: We aim to examine the relationships between substance use disorders and preventable hospitalizations for Ambulatory Care Sensitive Conditions among adult Medicaid beneficiaries. METHODS: Cross-sectional analysis using de identified Medicaid claims data in 2012 from 177,568 beneficiaries in Missouri was conducted. Logistic regression models were estimated for the associations of substance use disorder status with Ambulatory Care Sensitive Conditions, demographics, chronic physical and mental illnesses. Zero-inflated negative binomial regressions assessed substance use disorders, hospitalization for Ambulatory Care Sensitive Conditions, and length of hospital stay for Ambulatory Care Sensitive Conditions adjusting for co-morbid physical illnesses, mental illnesses and demographics. RESULTS: Over 12% of the sample had been diagnosed for substance use disorder. Beneficiaries with substance use disorder were more likely than Nonsubstance use disorder beneficiaries to have admissions for chronic conditions including short/long-term complications of diabetes, uncontrolled diabetes, hypertension, chronic obstructive pulmonary disease/asthma, but not for acute conditions. While substance use disorder beneficiaries were more likely than Nonsubstance use disorder beneficiaries to be hospitalized for any Ambulatory Care Sensitive Conditions; there were no statistical differences between the two groups in terms of length of hospital stays. CONCLUSIONS: Substance use disorder is statistically associated with hospitalizations for most Ambulatory Care Sensitive Conditions but not with length of hospital stay for Ambulatory Care Sensitive Conditions, after adjusting for covariates. The significant associations between substance use disorder and Ambulatory Care Sensitive Condition admissions suggest unmet primary health care needs for substance use disorder beneficiaries and a need for integrated primary/behavioral healthcare. PMID- 26844093 TI - Association between depressive symptoms in adolescence and birth outcomes in early adulthood using a population-based sample. AB - BACKGROUND: Adolescent female depressive symptomatology is an unrecognized mood disorder that impairs health in adolescence or adulthood. However, the long-term effects of pre-pregnancy depressive symptoms on birth outcomes in adulthood have not been given adequate empirical assessments. METHOD: In this study, we assessed the relationship between the life time duration of depressive symptoms over a 14 year period and birth outcomes (LBW and PTB) among a sample of 6023 female respondents who took part in the National Longitudinal Study of Adolescent to Adult Health (Add Health). We used the generalized estimating equation (GEE) models to assess these relationships. RESULTS: Exposure to elevated depressive symptoms in late adolescence, but not in adulthood, was associated with increased odds of LBW by more than 2-fold in early and young adulthoods (adjusted odds ratio [aOR] = 2.19; 95% confidence interval, CI: 1.56, 3.08). Depressive symptoms in early adulthood were independently associated with increased odds of PTB and were higher for black mothers. Maternal race modified the relationship between consistent reporting of depressive symptoms in adolescence and LBW or PTB in adulthood. CONCLUSION: This study provides compelling evidence that effects of elevated depressive symptomatology on LBW or PTB appear to be linked to a specific development period in adolescence. National policies to address social inequalities and stratification particularly in health at all stages of human development, will provide an important step in reducing depressive symptoms prior to early adulthood and in pregnancy and childbirth. PMID- 26844095 TI - The use of periodization in exercise prescriptions for inactive adults: A systematic review. AB - BACKGROUND: Periodization of exercise is a method typically used in sports training, but the impact of periodized exercise on health outcomes in untrained adults is unclear. PURPOSE: This review aims to summarize existing research wherein aerobic or resistance exercise was prescribed to inactive adults using a recognized periodization method. METHODS: A search of relevant databases, conducted between January and February of 2014, yielded 21 studies published between 2000 and 2013 that assessed the impact of periodized exercise on health outcomes in untrained participants. RESULTS: Substantial heterogeneity existed between studies, even under the same periodization method. Compared to baseline values or non-training control groups, prescribing periodized resistance or aerobic exercise yielded significant improvements in health outcomes related to traditional and emerging risk factors for cardiovascular disease, low-back and neck/shoulder pain, disease severity, and quality of life, with mixed results for increasing bone mineral density. CONCLUSIONS: Although it is premature to conclude that periodized exercise is superior to non-periodized exercise for improving health outcomes, periodization appears to be a feasible means of prescribing exercise to inactive adults within an intervention setting. Further research is necessary to understand the effectiveness of periodizing aerobic exercise, the psychological effects of periodization, and the feasibility of implementing flexible non-linear methods. PMID- 26844097 TI - Motivated to walk but nowhere to walk to: Differential effect of a mass media campaign by mix of local destinations. AB - OBJECTIVE: Built environment attributes are associated with walking but little is known about how the impact of walking campaigns varies across different environments. The objective of this study was to compare the impact of a campaign on changes in walking between respondents with a high versus low mix of local destinations. METHODS: Pre- and post-campaign data from a quasi-experimental study were used to compare changes in walking for residents aged 40-65 with high and low destination mix in a West Virginia community campaign (March-May 2005). RESULTS: Overall samples consisted of 777 intervention community respondents and 388 comparison community respondents with pre- and post-campaign data. Among insufficiently active intervention respondents, those with high destination mix increased their walking by 0.64 days more than those with low mix (p < 0.05). No significant differences were observed among the comparison community. CONCLUSION: The walking response to campaigns in those insufficiently active may be influenced by neighborhood attributes. PMID- 26844096 TI - Racial differences in parental perceptions of the neighborhood as predictors of children's physical activity and sedentary behavior. AB - OBJECTIVE: Most U.S. children engage in insufficient physical activity (PA) and spend too much time in sedentary behaviors (SBs), leading to increased risk of obesity and chronic disease. Evidence remains inconsistent on relationships between parental perceptions of the neighborhood and children's PA and SB. This study examines parental neighborhood perceptions, stratified by race, as predictors of children's PA and SB. METHODS: Relationships were tested with regressions stratified by parental race. The sample included 196 parents, residing in St. Louis, Missouri with a child at home. Participants responded to a mailed survey in 2012. Parental neighborhood perceptions were examined by mean composite scores and individual items. RESULTS: For parents of all races, perceived barriers negatively predicted the number of days in a week children engaged in >= 60 min of PA. Examining parental neighborhood perceptions by individual item, the perception that drivers exceed neighborhood speed limits was a positive predictor of their children's SB only among white parents. Only among minority-race parents was perceived neighborhood crime rate a positive predictor of their children's SB. CONCLUSIONS: While predictors of children's PA did not differ widely, several distinct predictors of children's SB by parental race lend support toward further examination of this topic. PMID- 26844098 TI - Characteristics associated with non-participation in 7-day accelerometry. AB - OBJECTIVE: To assess levels of physical activity the use of objective physical activity measures like accelerometers is promising. We investigated characteristics associated with non-participation in accelerometry within an apparently healthy sample. METHODS: Among German participants of a cardiovascular examination program (CEP; 2012-2013), 470 participants aged 40-75 years were invited to wear an accelerometer for 7 days. We used multivariate logistic regression to estimate the association between non-participation and the following characteristics of participants: sex, age, education, smoking, setting of recruitment for the CEP (general medical practices, job agencies, statutory health insurance), self-reported general health, and objective health criteria such as cardiorespiratory fitness and absolute number of cardiometabolic risk factors (elevated waist circumference, blood pressure, triglycerides, blood glucose, and reduced high-density lipoprotein). Subsequently, we stratified this analysis by sex. RESULTS: Among all invited individuals, N = 235 (60.0% women) gave consent to participate in accelerometry. Women were more likely to decline participation (odds ratio, 1.7; 95% confidence interval, 1.1-2.7) compared to men. Stratified analyses revealed the absolute number of risk factors as predictor of non-participation for men (1.4; 1.01-2.0), while there was no predictor found in women. CONCLUSION: We found a self-selection bias in participation in accelerometry. Women declined study participation more likely than men. The number of cardiometabolic risk factors decreased compliance only in men. Future studies should consider strategies to reduce this bias. PMID- 26844099 TI - Overweight and obesity among U.S. adults with and without disability, 1999-2012. AB - OBJECTIVE: Examine the relationship between disability and overweight/obesity among U.S. adults. METHODS: Study sample (N = 30,363) came from the National Health and Nutrition Examination Survey 1999-2012 waves. Disability was classified into five domains using standardized indices. Any disability was defined as having any difficulty in performing at least one of the activities in any of the five disability domains. Logistic regressions were conducted to estimate the association between disability and overweight/obesity, adjusted by individual characteristics and multiyear complex sampling design. RESULTS: Over a quarter (25.99%) of U.S. adults 20 years and older reported having any disability. The overweight/obesity rates across all disability domains were substantially higher than their nondisabled counterparts. The rate of overweight and obesity combined (BMI >= 25 kg/m(2)), obesity (BMI >= 30 kg/m(2)), grade 2 and 3 obesity combined (BMI >= 35 kg/m(2)), and grade 3 obesity (BMI >= 40 kg/m(2)) among people with any disability were 1.14 (73.54% versus 64.50%), 1.38 (41.37% versus 29.99%), 1.71 (19.81% versus 11.60%), and 1.94 (8.60% versus 4.43%) times the corresponding rate among people without disability, respectively. Compared with their nondisabled counterparts, the adjusted odds of overweight and obesity combined, obesity, grade 2 and 3 obesity combined, and grade 3 obesity were 24% (95% confidence interval [CI]: 14%-36%), 32% (95% CI: 22%-44%), 49% (95% CI: 35%-64%), and 55% (95% CI: 27%-89%) higher among people with any disability, respectively. CONCLUSION: People with disabilities have substantially higher risk of obesity compared to their nondisabled peers. PMID- 26844100 TI - Health behaviors of mandated and voluntary students in a motivational intervention program. AB - College students engage in many unhealthy behaviors, one of these, heavy alcohol use, is a major global public health problem. OBJECTIVE: This longitudinal study examined whether students' mandated/voluntary status in a program to reduce college drinking was associated with overall health, ethnicity, gender, and personality traits. Both mandated and voluntary groups participated in the Motivational Intervention (MI) program to prevent high risk drinking. METHODS: Freshmen (710 voluntary, 190 mandated, n = 900) between the ages of 18 and 21, received the MI at baseline and again at 2 weeks, with boosters at 3, 6 and 12 months. Participants completed three measures: the Daily Drinking Questionnaire (DDQ); the Substance Use Risk Profile Scale (SURPS), and the Health Promoting Lifestyle Profile II (HPLPII). Mandated and voluntary participants were compared at baseline and following the intervention using two sample t-tests for continuous variables (overall health, personality traits, drinking measures), and chi-square for categorical variables (gender, ethnicity). Linear mixed models were used to identify associations between HPLP II scores and mandated/voluntary status, time, ethnicity gender and SURPS scale scores. RESULTS: In both groups, alcohol consumption dropped significantly by 12 months. Overall health-promoting behaviors, physical activity, stress management, and interpersonal relations improved in both groups between baseline and 12 months. Associations were found between alcohol consumption, personality traits, gender, and lifestyle health promoting behaviors. In particular, impulsivity and hopelessness were associated with poor health behaviors. CONCLUSIONS: Intervention programs to reduce drinking by college students need to address developmental dynamics of freshmen students, including gender, psychosocial factors, personality, and lifestyle health promoting behaviors. PMID- 26844101 TI - Changes in mode of transportation to work or school from pre-pregnancy to early pregnancy in the Norwegian Fit for Delivery study. AB - OBJECTIVE: To describe changes in mode of transportation to work or school from pre-pregnancy to early pregnancy, to describe levels of physical activity related to mode of transportation to work or school, and to examine associations between changes in mode of transportation to work or school and educational level, body mass index (BMI) and age. METHODS: Between September 2009 and February 2013, 575 healthy pregnant nulliparous women were included into the Norwegian Fit for Delivery (NFFD) trial. At inclusion they reported their current and their pre pregnancy mode of transportation to work or school. Data were analysed by multilevel mixed models with dichotomized modes of transportation as dependent variables. RESULTS: There was a significant change towards less active transportation to work or school and a decrease in level of physical activity from pre-pregnancy to early pregnancy. Pre-pregnancy, 58% used private transportation to work or school, compared to 64% in early pregnancy (p = 0.001). The percentage of women who biked (11% v. 5%, p < 0.001) decreased significantly from pre-pregnancy to early pregnancy. CONCLUSIONS: In this sample of Norwegian women there was a significant change towards less active transportation to work or school and lower levels of physical activity from pre-pregnancy to early pregnancy. PMID- 26844102 TI - Lifestyle interventions for type 2 diabetes prevention in women with prior gestational diabetes: A systematic review and meta-analysis of behavioural, anthropometric and metabolic outcomes. AB - PURPOSE: To systematically review lifestyle interventions for women with prior Gestational Diabetes Mellitus (GDM) to report study characteristics, intervention design and study quality and explore changes in 1) diet, physical activity and sedentary behaviour; 2) anthropometric outcomes and; 3) glycaemic control and diabetes risk. METHODS: Databases (Web of Science, CCRCT, EMBASE and Science DIRECT) were searched (1980 to April 2014) using keywords for controlled or pre post design trials of lifestyle intervention targeting women with previous GDM reporting at least one behavioural, anthropometric or diabetes outcome. Selected studies were narratively synthesized with anthropometric and glycaemic outcomes synthesized using meta-analysis. RESULTS: Three of 13 included studies were rated as low bias risk. Recruitment rates were poor but study retention good. Six of 11 studies reporting on physical activity reported favourable intervention effects. All six studies reporting on diet reported favourable intervention effects. In meta-analysis, significant weight-loss was attributable to one Chinese population study (WMD = - 1.06 kg (95% CI = - 1.68, - 0.44)). Lifestyle interventions did not change fasting blood glucose (WMD = - 0.05 mmol/L, 95% CI = - 0.21, 0.11) or type 2 diabetes risk. CONCLUSIONS: Lack of methodologically robust trials gives limited evidence for the success of lifestyle interventions in women with prior GDM. Recruitment into trials is challenging. PMID- 26844103 TI - Association between self-reported and objectively measured physical fitness level in a middle-aged population in primary care. AB - AIM: To investigate the association between self-reported physical fitness level obtained by a single-item question and objectively measured fitness level in 30- to 49-year-old men and women. METHODS: From the Danish 'Check Your Health Preventive Program' 2013-2014 fitness level was assessed in 2316 participants using the Aastrand test. Additionally, participants rated their physical fitness as high, good, average, fair or low. The association of self-reported- with objectively measured fitness level was analyzed by linear regression. Categories of self-reported- and objectively measured fitness level were cross-tabulated and agreement was quantified by Kappa statistics. Gender differences within categories were investigated by Poisson regression. RESULTS: Data from 996 men and 1017 women were analyzed (excluded, n = 303). In both men and women a higher self-reported fitness level was associated with a higher objectively measured fitness level (Rall = 0.42). Kappa agreement was 0.25. Poisson regression revealed that women rated their fitness level significantly lower than men (p < 0.001). CONCLUSION: A single-item question is a cost-effective way of measuring physical fitness level, but the method has low association and fair agreement when compared to the Aastrand test. Men tend to overestimate physical fitness more than women, which should be accounted for if using the question in primary care settings. PMID- 26844104 TI - Physicians', nurses' and community health workers' knowledge about physical activity in Brazil: A cross-sectional study. AB - OBJECTIVES: To measure knowledge of current recommendations of physical activity and consequences of physical inactivity among healthcare providers throughout Brazil. METHODS: A phone survey of 1600 randomly selected primary healthcare units in Brazil was conducted between January and July 2011. At each unit, a physician, nurse or community healthcare worker (n = 798) responded to a 40 minute survey, eliciting information about demographics, knowledge, and health behaviors pertaining to physical activity. RESULTS: Among nurses and community healthcare workers, > 95% reported needing more information on physical activity guidelines. Among physicians this proportion was 80%. Nearly 40% of the professionals incorrectly believed 90-min of moderate-intensity physical activity per week is the recommended amount for health benefits; nearly 30% believed that 90-min of vigorous-intensity activity per week is needed for the same purpose. More than 75% of all groups reported that type II diabetes, hypertension, depression, and coronary heart disease might result from physical inactivity, but on average only 60% from each group are aware of osteoporosis as a possible consequence of physical inactivity. CONCLUSIONS: Training health professionals in how to convey all relevant information about physical activity to their patients is critical for health promotion within the primary care system in Brazil. PMID- 26844109 TI - An Australian survey of cognitive health beliefs, intentions, and behaviours through the adult life course. AB - OBJECTIVE: Information is required regarding cognitive health beliefs and behaviours from across the life in order to inform the design of interventions to optimise cognitive health and reduce the risk of cognitive impairment. METHODS: A survey of Australian adults aged 20-89 was administered via Computer Assisted Telephone Interviewing (CATI) software to respondents recruited by random digit dialling (N = 900). Socio-demographic and self-reported health information was collected to investigate associations with cognitive health responses. RESULTS: Alcohol abuse was nominated by the highest proportion of respondents (34.3%) as detrimental for brain health. Fewer than 5% nominated elevated cholesterol, blood pressure, obesity, poor education, or ageing. The most frequently endorsed protective activity was socialising (70%). Socio-demographic factors predicted responses. Age-group differences were apparent in the proportions nominating alcohol (X(2) = 24.2; p < .001), drugs (X(2) = 56.8; p < .001), smoking (X(2) = 13.1; p = .001), nutrition (X(2) = 20.4; p < .001), and mental activity (X(2) = 12.8; p = .002) as relevant to brain health. Activities undertaken for cognitive benefit also differed by age. Across all ages the perceived benefit of activities was not supported by intentions to undertake activities. CONCLUSIONS: Interventions are needed to inform and motivate people across the life-course to undertake behaviours specifically to optimise their cognitive health. PMID- 26844108 TI - Exercise is MedicineTM: A pilot study linking primary care with community physical activity support. AB - INTRODUCTION: Exercise is MedicineTM (EIM) is an approach to clinic-based physical activity (PA) promotion. Study aims were to 1) assess the acceptability of current EIM protocols among healthcare providers (providers) and health and fitness professionals (fitness professionals); and 2) pilot test the resultant modified EIM protocols comparing patients referred to community PA programming with patients exposed to the EIM protocols alone. METHODS: During 2012-2013 in Chattanooga, Tennessee, USA, 30/80 invited providers and 15/25 invited fitness professionals received training and provided feedback in the use of the EIM protocols. Following EIM use, feedback from providers and fitness professionals about acceptability of EIM protocols resulted in the adaptation of EIM protocols into the electronic health record. Subsequently, 50 providers and 8 fitness professionals participated in the intervention phase of the pilot study. Healthy and/or disease managed adults 18 years and older were enrolled with a sample of patients exposed to both the EIM protocols and community PA programming (EIM +) while another sample was exposed to the EIM protocols only (EIM). All patients were assessed for physical activity and Health-related Quality of Life. Measures were repeated ~ 3 months later for each patient. RESULTS: Eighteen EIM + and 18 EIM participants were studied. The EIM + participants had a greater net increase in total PA (?[Formula: see text] = + 250 min/week) vs. EIM participants (?[Formula: see text] = - 38.6 min/week) (p = 0.0002). CONCLUSIONS: EIM + participation significantly increased PA levels among participants, suggesting this approach significantly impacts the PA of inactive adults more than just EIM only. PMID- 26844106 TI - Physical activity levels and obesity status of Oregon Rural Elementary School children. AB - OBJECTIVE: To evaluate the relationship between physical activity (PA, min/school day) at school and body mass index (BMI, kg/m(2)) among rural elementary-aged children. METHODS: Height (cm), weight (kg), and PA were measured for 1767 children (5-12 years) enrolled in six rural Oregon elementary schools in fall, 2013. PA at school was measured over four days using Walk4Life pedometers. Children with >= 3 valid monitoring days (n = 1482) were included in analyses. Means (min/d) were calculated for wear time, total PA (TPA: combined light, moderate, vigorous PA), and moderate to vigorous PA (MVPA: step count > 120/min). BMI z-scores were calculated and regression models were run to examine the relationship between PA and BMI z-scores, adjusting for wear time, sex, and grade. RESULTS: Overweight (38.1%: BMI >= 85(th) percentile for age and sex) and obesity (19.4%: BMI >= 95(th) percentile) prevalence was similar for boys (n = 782) and girls (n = 700). More MVPA was associated with lower BMI (P < 0.001), independent of sex, wear time or grade. Mean MVPA was 18.9 +/- 8 min/d, versus 15.2 +/- 6.7 min/d for healthy-weight and obese children, respectively. CONCLUSIONS: Children are not meeting minimum MVPA recommendations (60 min/d) during school hours. Efforts to promote PA for obesity prevention in rural elementary schools should focus on increasing opportunities for MVPA. PMID- 26844105 TI - Associations between parenting partners' objectively-assessed physical activity and Body Mass Index: A cross-sectional study. AB - OBJECTIVE: Family members have the capacity to influence each other's health behaviours. This study examined whether there were associations in the objectively assessed physical activity and Body Mass Index (BMI) of mothers and fathers. METHODS: Recruitment took place in Bristol (UK) during 2012/13. Participants were 272 pairs of parents (dyads) that wore an accelerometer for at least 500 min on 3 or more days. Parents provided demographic information and self-reported height and weight. Multi-variable linear and logistic regression models examined the relationships between parents' moderate-to-vigorous physical activity (MVPA) and BMI. RESULTS: MVPA minutes (r = 0.26, p < 0.001) and Body Mass Index (r = 0.20, p = 0.002) of parents were correlated. Logistic regression analysis showed that mothers were almost twice (OR 1.87, p < 0.05) as likely to be overweight or obese when fathers were. Linear regression models showed that at the weekend every 9 min of paternal MVPA was associated with 3 min of maternal MVPA (r = 0.34, p < 0.001). CONCLUSIONS: Both physical activity and BMI of parenting partners were associated. Since parents tend to share home environments and often perform activities together or as a family, then behavioural changes in one parent may have a ripple effect for other family members. PMID- 26844110 TI - Small area-level socioeconomic status and all-cause mortality within 10 years in a population-based cohort of women: Data from the Geelong Osteoporosis Study. AB - BACKGROUND: The social gradient of health and mortality is well-documented. However, data are scarce regarding whether differences in mortality are observed across socio-economic status (SES) measured at the small area-level. We investigated associations between area-level SES and all-cause mortality in Australian women aged >= 20 years. METHODS: We examined SES, obesity, hypertension, lifestyle behaviors and all-cause mortality within 10 years post baseline (1994), for 1494 randomly-selected women. Participants' residential addresses were matched to Australian Bureau of Statistics Census data to identify area-level SES, and deaths were ascertained from the Australian National Deaths Index. Logistic regression models were adjusted for age, and subsequent adjustments made for measures of weight status and lifestyle behaviors. RESULTS: We observed 243 (16.3%) deaths within 10 years post-baseline. Females in SES quintiles 2-4 (less disadvantaged) had lower odds of mortality (0.49-0.59) compared to SES quintile 1 (most disadvantaged) under the best model, after adjusting for age, smoking status and low mobility. CONCLUSIONS: Compared to the lowest SES quintile (most disadvantaged), females in quintiles 2 to 5 (less disadvantaged) had significantly lower odds ratio of all-cause mortality within 10 years. Associations between extreme social disadvantage and mortality warrant further attention from research, public health and policy arenas. PMID- 26844107 TI - Trends in cigarette, cigar, and smokeless tobacco use among New York City public high school youth smokers, 2001-2013. AB - OBJECTIVE: This study aimed to describe the recent trends in youth smoking behaviors, and examine cigar and smokeless tobacco use patterns among youth smokers in New York City. METHODS: Data, analyzed in 2014, were from the New York City Youth Risk Behavior Survey, a cross-sectional survey conducted bi-annually since 1997 in a representative sample of New York City public high school students (2001-2013), n = 59,122. RESULTS: Cigarette smoking declined 53%, from 17.6% in 2001 to 8.2% in 2013 (p < 0.001). The proportion of cigar use among smokers doubled, from 22.2% in 2001 to 45.9% in 2013 (p < 0.001), while the proportion of smokeless tobacco use among smokers increased by 400% between 2001 and 2013 (4.2% vs. 21.2%, p < 0.001). CONCLUSIONS: Youth cigarette smoking rates in New York City decreased, while cigar smoking and smokeless tobacco use among smokers increased considerably. These data highlight trends in youth smoking behaviors within the context of New York City's comprehensive tobacco control program and stress the need for additional activity to spur further declines in cigarette smoking and reverse the trends in cigar and smokeless tobacco use among New York City youth. Results demonstrate the need for continuous surveillance and action by the public health community to counteract tobacco industry promotion of other products. PMID- 26844111 TI - Correlates of mobile phone use in HIV care: Results from a cross-sectional study in South Africa. AB - OBJECTIVE: Human Immunodeficiency Virus (HIV) is a major disease burden worldwide. Challenges include retaining patients in care and optimizing adherence to Antiretroviral Therapy (ART). One possible solution is using mobile phones as reminder tools. The main aim of our study was to identify patient demographic groups least likely to use mobile phones as reminder tools in HIV care. DESIGN: The data came from a cross-sectional study at the Chris Hani Baragwanath Hospital, Soweto Township, South Africa. METHODS: A comprehensive questionnaire was used to interview 883 HIV infected patients receiving ART. Logistic regression analysis was performed to identify the influence of age, gender, education level, marital status, number of sexual partners in the last three months, income level, and employment status on the use of mobile phone as reminders for clinic appointments and taking medication. RESULTS: Patient groups significantly associated with being less likely to use mobile phones as clinic appointment reminders were: a) patients 45 years or older, b) women, and c) patients with only primary or no schooling level. Patient groups significantly associated with being less likely to use mobile phones as medication reminders were: a) patients 35 years or older and b) patients with a lower monthly income. CONCLUSIONS: In this setting being a woman, of older age, lower education, and socio-economic level were risk factors for the low usage of mobile phones as reminder aids. Future studies should assimilate reasons for this, such that patient-specific barriers to implementation are identified and interventions can be tailored. PMID- 26844113 TI - Choosing between stairs and escalators in China: The impact of location, height and pedestrian volume. AB - OBJECTIVE: This research examines whether Beijing residents are more or less likely than Montreal residents to avoid stair climbing, by replicating a study in Montreal, Canada that measured the impacts of distance between stairs and escalator, height between floors and pedestrian volume on stair climbing rate. METHOD: 15 stairways, 14 up-escalators and 13 down-escalators were selected in 13 publicly accessible settings in Beijing. Distance between the bottom or top of nearest stair and escalator combinations varied from 2.1 m to 114.1 m with height between floors varying from 3.3 m to 21.7 m. Simultaneous counts were conducted on stair and escalator pairs, for a total of 37,081 counted individuals. RESULTS: In the ascent model, pedestrian volume accounted for 16.3% of variance in stair climbing, 16.4% when height was added and 45.1% when distance was added. In the descent model, 40.9% of variance was explained by pedestrian volume, 41.5% when height was added and 45.5% when distance was added. CONCLUSION: Separating stairs and escalator is effective in increasing stair climbing in Beijing, accounting for 29% of the variance in stair climbing, compared with 43% in Montreal. As in the Montreal case, distance has less effect on stair use rate when descending. Overall, 25.4% of Beijingers opted for stairs when ascending compared with 20.3% of Montrealers, and for descending 32.8% and 31.1% respectively. PMID- 26844112 TI - The role of knowledge, language, and insurance in endorsement of cancer screening in women of African origin. AB - BACKGROUND: African women have lower use of cancer screening services compared to women born in the United States yet empirical data are limited about their cancer screening attitudes. OBJECTIVE: To examine factors that are associated with higher endorsement of screening. METHOD: We conducted a cross-sectional study of 200 women of African origin recruited via community-based outreach activities in Washington, DC. Endorsement of screening was assessed via self-report. The primary independent variables were cancer knowledge and English-language proficiency. Information was also collected about access, cancer-related beliefs, and prior breast screening behaviors. RESULTS: Most participants (60%) were >= 40 years of age, 54% were married, and 77% were insured. Participants more likely to endorse breast cancer screening were insured (vs. uninsured) (odds ratio = 3.37; 95% confidence interval: 1.24, 9.17) and married (odds ratio = 3.23; 95% confidence interval: 1.14, 9.10) controlling for other factors. The likelihood of endorsing screening was higher among participants with English as a primary language (odds ratio = 3.83; 95% confidence interval: 1.24, 11.87) and those with greater breast cancer knowledge (odds ratio = 1.04; 95% confidence interval: 1.01, 1.08, per 1 point increase). CONCLUSIONS: Average cancer knowledge in the sample was low as were non-conventional causes of cancer. Study results highlight the importance of improving cancer knowledge and reducing barriers related to language and insurance. Future studies are needed to consider nuances among diverse women of African origin. PMID- 26844114 TI - The relationship between interviewer-respondent race match and reporting of energy intake using food frequency questionnaires in the rural South United States. AB - OBJECTIVE: The purpose of the observational study was to determine whether interviewer race influences food frequency questionnaire (FFQ) reporting accuracy in a Deep South, largely African American cohort. METHODS: A secondary analysis was conducted to investigate the influence of interviewer race on energy reporting of 319 African Americans who participated in the Mississippi Communities for Healthy Living intervention in May-June 2011, a community-based and USDA-funded project. Reported energy intake was compared to total energy expenditure to identify normal (ENR), under-(EUR) and over-reporters (EOR). Multivariate logistic regression models determined the relationship between race match and energy misreporting, accounting for confounding variables (educational level, health status perception, BMI, gender, and age) identified using chi square/correlation analyses. RESULTS: The sample included 278 African Americans with 165 EURs, 26 EORs, and 87 ENRs identified. Logistic regression analyses revealed that there was no relationship between race-matched participants and EUR or EOR; controlling factors, BMI and perceived health status were significant in the model. CONCLUSION: This study is the first to our knowledge to examine whether race influences dietary intake reporting which may influence assessment data used for comparison with health outcomes. This may have important implications for research conducted in health disparate populations, particularly rural, Southern populations. PMID- 26844115 TI - Effects of walking on low-grade inflammation and their implications for Type 2 Diabetes. AB - OBJECTIVE: Inflammatory cytokines released by hypertrophic adipocytes contribute to low-grade inflammation, a characteristic of Type 2 Diabetes. Skeletal muscle contraction during physical activity stimulates the secretion of anti inflammatory cytokines able to counteract this inflammatory status. The aim of this study was to review the evidence of the effectiveness of walking as a physical activity intervention to reduce inflammation. The interplay between adipose tissue and skeletal muscle contributions was also investigated. METHOD: A structured literature review of papers available up to December 2014 was carried out within the PubMed, Scopus and ISI Web of Science databases using the keywords "walking" and "inflammation" in order to identify the studies involving healthy subjects and subjects diagnosed with, or at increased risk of, Type 2 Diabetes. RESULTS: Thirty-two studies were reviewed, five investigating the acute effects of walking and twenty-seven its chronic effects (n = 21 interventional and n = 6 observational). Acute effects of walking bouts led to an increase of interleukin 6 in one study, although without any increase in the concentration of the anti inflammatory marker interleukin-1 receptor antagonist. Eight interventional studies showed a significant reduction of inflammation. A reduction in tumour necrosis factor-alpha concentration was often associated with an adiposity reduction. The observational studies showed that individuals who walk more present a lower inflammatory status. CONCLUSION: There is no consensus regarding the efficacy of walking in the reduction of low-grade systemic inflammation, even though a relationship cannot be excluded. In each walking bout, no anti inflammatory effect due to the IL-6-stimulated myokine cascade can be demonstrated. PMID- 26844116 TI - Are children's activity levels determined by their genes or environment? A systematic review of twin studies. AB - CONTEXT: The importance of physical activity to paediatric health warrants investigation into its determinants. Objective measurement allows a robust examination of genetic and environmental influences on physical activity. OBJECTIVE: To systematically review the evidence on the extent of genetic and environmental influence on children's objectively-measured activity levels from twin studies. DATA SOURCES AND SEARCH TERMS: Medline, EMBASE, PsycINFO, Health and Psychosocial Instruments and all Ovid Databases. Search terms: "accelerometer" OR "actometer" OR "motion sensor" OR "heart rate monitor" OR "physical activity energy expenditure" AND "twin". Limited to Human, English language and children (0-18 years). RESULTS: Seven sets of analyses were included in the review. Six analyses examined children's daily-life activity and found that the shared environment had a strong influence on activity levels (weighted mean 60%), with a smaller contribution from genetic factors (weighted mean 21%). Two analyses examined short-term, self-directed activity in a standard environment and found a smaller shared environment effect (weighted mean 25%) and a larger genetic estimate (weighted mean 45%). CONCLUSIONS: Although genetic influences may be expressed when children have brief opportunities for autonomous activity, activity levels in daily-life are predominantly explained by environmental factors. Future research should aim to identify key environmental drivers of childhood activity. PMID- 26844117 TI - Parental education and text messaging reminders as effective community based tools to increase HPV vaccination rates among Mexican American children. AB - OBJECTIVE: Latino populations, particularly Mexican-Americans who comprise 65% of the Latinos in the U.S., are disproportionately affected by HPV-related diseases. The HPV vaccination completion rates remain low, well below the Healthy People 2020 goal. In this study we assessed the effect of parental education and a text messaging reminder service on HPV vaccine completion rates among eligible children of Mexican American parents. STUDY DESIGN: Nonequivalent group study of Mexican parents of HPV vaccine eligible children attended the Health Window program at the Mexican Consulate in New York City, a non-clinical, trusted community setting, during 2012-2013. 69 parents received HPV education onsite, 45 of whom also received a series of text message vaccination reminders. We measured HPV vaccination completion of the youngest eligible children of Mexican parents as the main outcome. RESULTS: 98% of those in the education plus text messaging group reported getting the first dose of the vaccine for their child and 87% among those in the educational group only (p = 0.11). 88% of those receiving the 1st dose in the text messaging group reported completing the three doses versus 40% in the educational group only (p = 0.004). CONCLUSIONS: Parental text messaging plus education, implemented in a community based setting, was strongly associated with vaccine completion rates among vaccine-eligible Mexican American children. Although pilot in nature, the study achieved an 88% series completion rate in the children of those who received the text messages, significantly higher than current vaccination levels. PMID- 26844118 TI - Screening mammography uptake within Australia and Scotland in rural and urban populations. AB - OBJECTIVE: To test the hypothesis that rural populations had lower uptake of screening mammography than urban populations in the Scottish and Australian setting. METHOD: Scottish data are based upon information from the Scottish Breast Screening Programme Information System describing uptake among women residing within the NHS Highland Health Board area who were invited to attend for screening during the 2008 to 2010 round (N = 27,416). Australian data were drawn from the 2010 survey of the 1946-51 cohort of the Australian Longitudinal Study on Women's Health (N = 9890 women). RESULTS: Contrary to our hypothesis, results indicated that women living in rural areas were not less likely to attend for screening mammography compared to women living in urban areas in both Scotland (OR for rural = 1.17, 95% CI = 1.06-1.29) and Australia (OR for rural = 1.15, 95% CI = 1.01-1.31). CONCLUSIONS: The absence of rural-urban differences in attendance at screening mammography demonstrates that rurality is not necessarily an insurmountable barrier to screening mammography. PMID- 26844119 TI - Patterns of folic acid use in pregnant Saudi women and prevalence of neural tube defects - Results from a nested case-control study. AB - BACKGROUND: Although the role of folic acid (FA) in preventing neural tube defects (NTDs) is well documented, its optimal intake in pregnant women is still low in many countries. Here, we prospectively studied the prevalence of NTDs in the newborns and the patterns of FA intake in pregnant Saudi mothers. METHODS: This case-control study was nested within a 3-year project (July 2010 to June 2013) to study the patterns of birth defects in the offspring of Saudi women who received their antenatal care and delivered at Prince Sultan Military Medical City, Riyadh-Saudi Arabia. Enrolled mothers were divided into 4 groups: group 1 (FA taken before pregnancy and continued regularly after conception), group 2 (FA taken post-conception), group 3 (no FA intake), and group 4 (did not remember or were unsure of taking FA). Control mothers were randomly selected from those with normal first obstetrical ultrasound scan at 18-22 weeks of gestation. RESULTS: The cohort included 30,531 mothers giving birth to 28,646 infants. We studied 1179 mothers of babies with birth defects (BDs) and 1262 control mothers. There were 237 (9.7%) mothers in-group 1; 2001 (82%) in-group 2; 154 (6.3%) in-group 3; and 49 (2%) in-group 4. There were 49 babies with NTDs, a prevalence of 1.7/1000 total births. Among the studied mothers 2274 (93%) took FA either full or partial course. CONCLUSION: The high prevalence of NTDs and the low optimal FA intake highlight the need for a strict implementation of staple food fortification and health education program for Saudi women. PMID- 26844120 TI - Patient-provider discussions about lung cancer screening: Results from the 2012/2013 Kansas Adult Tobacco Survey. AB - OBJECTIVE: Prior to the 2013 US Preventive Services Task Force (USPSTF) guidelines for lung cancer screening, the American Cancer Society released interim guidance recommending physicians discuss lung cancer screening with high risk patients. We included a question on patient-provider discussions about lung cancer screening on a statewide population-based survey to establish baseline prevalence for surveillance and to identify subpopulation disparities. METHODS: We analyzed the 2012/2013 Kansas Adult Tobacco Survey to assess patient-provider discussions about lung cancer screening. Weighted prevalence estimates and adjusted odds ratios were calculated to examine characteristics associated with discussing screening. RESULTS: The prevalence of patient-provider discussions about lung cancer screening among current and former smokers aged 55 to 74 years was 31.0% (95% CI 27.0-35.0). The adjusted prevalence odds of having these discussions was higher among males, adults aged 65 to 74 years, adults living with a disability, as well as those who saw a health professional in the past year and had their smoking status assessed or were advised to quit. CONCLUSIONS: The current study is unique as it is the first to assess patient-provider discussions about lung cancer screening using a statewide survey. These results may inform strategies to increase patient-provider discussions about lung cancer screening among high risk Kansans. PMID- 26844121 TI - Rationale, design and respondent characteristics of the 2013-2014 New York City Health and Nutrition Examination Survey (NYC HANES 2013-2014). AB - PURPOSE: Capacity to monitor non-communicable diseases (NCDs) at state or local levels is limited. Emerging approaches include using biomeasures and electronic health record (EHR) data. In 2004, New York City (NYC) performed a population based health study on adult residents using biomeasures (NYC Health and Nutrition Examination Study, or NYC HANES), modeled after NHANES. A second NYC HANES was launched in 2013 to examine change over time, evaluate municipal policies, and validate a proposed EHR-based surveillance system. We describe the rationale and methods of NYC HANES 2013-2014. METHODS: NYC HANES was a population-based, cross sectional survey of NYC adults using three-stage cluster sampling. Between August 2013 and June 2014, selected participants completed a health interview and physical exam (blood pressure, body mass index, and waist circumference). Fasting biomeasures included diabetes, lipid profiles, kidney function, environmental biomarkers, and select infectious diseases. RESULTS: Of the 3065 households approached, 2742 were eligible and 1827 were successfully screened (67%). A total of 1524 of eligible participants completed the survey (54%), for an overall response rate of 36%. CONCLUSION: Completing a second NYC HANES a decade after the first study affords an opportunity to understand changes in prevalence, awareness and control of NCDs and evaluate municipal efforts to manage them. PMID- 26844123 TI - Concurrent healthy behavior adoption and diabetic retinopathy in the United States. AB - OBJECTIVE: Emerging work suggests an independent association of physical activity and healthy eating on diabetic retinopathy. No study, however, has examined whether physical activity and healthy eating have an additive and/or additive interaction effect on diabetic retinopathy. METHODS: Data from 2005-2006 NHANES were used (N = 223). Physical activity was assessed via accelerometry; healthy eating was assessed from an interview with the Healthy Eating Index calculated to represent healthy eating; and diabetic retinopathy was assessed from the Canon Non-Mydratic Retinal Camera CR6-45NM. RESULTS: Physical activity (OR = 0.70, p = 0.42) and healthy eating (OR = 0.36, p = 0.16) were not independently associated with moderate-to-severe retinopathy. However, individuals with both health behaviors, compared to none, had a reduced odds of moderate-to-severe retinopathy (OR = 0.03, p = 0.02). Further, the attributable proportion (AR = 0.57, 95% CI 0.02-1.12, p < 0.05) was significant, suggesting that a significant proportion of retinopathy may be attributed to the additive interaction between inactivity and unhealthy eating. CONCLUSION: The concurrent presence of physical activity and healthy eating was associated with reduced odds of diabetic retinopathy, with the additive interaction effects suggesting that this observed association is more than summation. PMID- 26844122 TI - Impact of a chronic disease self-management program on healthcare utilization in eastern Ontario, Canada. AB - This study aims to examine patients' patterns of health care utilization before and after participation in a Chronic Disease Self-Management Program (CDSMP). We conducted a pre-post study using health care administrative data from 186 individuals in the Ottawa region who participated in our CDSMP between September 2009 and January 2011. We collected the number of general practitioner/specialist visits, planned/unplanned emergency department visits, and hospitalizations, measured 6 months and 1 year before and after participation in the CDSMP. Multivariate analysis was performed to identify associations between patient characteristics and pre-post CDSMP health care utilization. CDSMP participation showed no effect on number of physician visits, hospitalizations, or emergency department visits. Individuals with > 5 chronic conditions were more likely to visit a physician and the emergency department following the CDSMP than those with 1 chronic condition. Among individuals > 61 years of age, those with the marital status widowed were more likely to visit their physician and the emergency department following the CDSMP than married individuals. To conclude, the CDSMP appeared not to decrease health care utilization. Low baseline utilization rates, short-term follow-ups, and a relatively healthy patient population may have contributed to the program's low impact. PMID- 26844124 TI - A novel approach to the issue of physical inactivity in older age. AB - OBJECTIVE: Well-designed exercise can prevent falls in older people but previous research indicates that promoting general physical activity may increase falls. This study aimed to evaluate uptake and adherence to a physical activity promotion and fall prevention intervention among community-dwelling people aged 60 + years. METHODS: This was a process evaluation of intervention group data from an ongoing randomised controlled trial. Participants were 38 Australian community-dwelling older people assigned to intervention group who had completed 3 months of a physical activity and fall prevention intervention. Study measures included baseline daily step count assessed by Actigraph accelerometers, 12 week follow-up step count assessed by Fitbit pedometers and rating of participant engagement with the health coaching intervention. RESULTS: 35 participants remained in the study at week 12 and were analysed. Mean daily steps significantly increased in week 12 compared with steps at baseline (change in mean = 1101 steps, 95% CI: 285-1917, p = 0.01). Health coaching engagement was rated as high for 19 people (54%), medium for 12 (34%) and low for 4 people (12%). All participants used the Fitbit to provide feedback about daily activity. CONCLUSION: The excellent intervention compliance and promising physical activity results demonstrate the acceptability and feasibility of this novel intervention. PMID- 26844125 TI - Temperament and Objectively Measured Physical Activity and Sedentary Time among Canadian Preschoolers. AB - This study sought to assess the influence of preschoolers' temperament on their objectively measured physical activity and sedentary time. ActicalTM accelerometers were used to measure preschoolers' from London, Canada's (n = 216; 2.5-5 years) physical activity and sedentary levels during childcare hours (5 consecutive days; 15 s epoch). The Child Temperament Questionnaire (CTQ) was used to assess child temperament via parent/guardian report. The six subscales of the CTQ (i.e., reaction to food, soothability, attention span, activity, sociability, and emotionality) were correlated with Actical data (i.e., sedentary time, moderate-to-vigorous physical activity, and total physical activity). The five items of the activity subscale were correlated with these three measures of sedentary time and physical activity. Pearson product-moment correlation coefficients were employed for both sets of analyses. Of the correlations examined, few had an absolute value greater than 0.10, and none were statistically significant after taking multiple comparison bias into account. The results of this work might provide additional indirect support for the conclusion that the childcare environment should be a primary focus with regard to the promotion of increased physical activity and decreased sedentary time among preschoolers. Additional research is required to confirm the relationship between preschoolers' temperament and levels of physical activity and sedentary time. PMID- 26844126 TI - Farmers sun exposure, skin protection and public health campaigns: An Australian perspective. AB - Non-melanoma skin cancer is a common and costly cancer in agricultural populations. Prevention and early detection are an effective way to decrease the burden of disease and associated costs. To examine sun exposure and skin protection practices in agricultural workers and farmers a thematic review of the literature between 1983 and 2014 was undertaken. Comparison between studies was complicated by differences in study design, definitions of skin protection, and analytic methods used. Farmers are the most exposed to harmful ultraviolet (UV) radiation of all outdoor workers and the level of reported skin protection by farmers is suboptimal. Years of public health campaigns have failed to adequately address farmers' specific needs. Increased rates of skin cancer and subsequent higher costs are expected. Estimates of sun exposure and skin protection practice indicate that protective clothing is the most promising avenue to improve on farmers' skin protection. Early detection needs to be part of public health campaigns. This review explores the quantitative data about Australian farmers and their skin protective behaviours. We investigate what the documented measurable effect of the public health campaign Slip!Slop!Slap! has had on agricultural workers and farmers and make recommendations for future focus. PMID- 26844127 TI - Perceived discrimination in U.S. healthcare: Charting the effects of key social characteristics within and across racial groups. AB - This article employs an original empirical analysis to contribute to scientific understandings of the relationship between social characteristics and perceptions of discrimination in healthcare encounters within and across racial categories in the U.S. Our analysis focuses on a diverse sample of 43,020 adults aged 18 to 85 drawn from the California Health Interview Survey (CHIS). We use a series of weighted descriptive statistics and logistic regression models to parse out factors associated with perceived discrimination and chart how they vary by race and ethnicity. Members of racial minorities were more likely to report perceptions of discrimination, and while the effect was somewhat mitigated by introducing patient and health-care system factors into our models, the race effects remained both statistically significant and of substantial magnitude (particularly for African Americans and Native Americans). Poor self-reported health and communication difficulties in the clinical encounter were associated with increased perceptions of discrimination across all groups. Further, among non-whites, increased education was associated with increased perceptions of discrimination net of other factors. These findings suggest efforts to reduce disparities in medical care should continue to focus on expanding the depth and quality of patient-provider interactions for disadvantaged racial groups, while also being attentive to other factors that affect perceived racial discrimination in healthcare encounters within and across racial groups. PMID- 26844128 TI - Effect of wrist-worn activity monitor feedback on physical activity behavior: A randomized controlled trial in Finnish young men. AB - The purpose of this study is to evaluate whether the use of an activity monitor providing feedback has an effect on physical activity (PA) in young men. A population-based sample of 276 conscription-aged (mean = 17.9, SD = 0.7 years) men participated in a 3-month randomized controlled trial in Oulu in 2012. Participants were randomized to an intervention group (INT, N = 137) and a control group (CON, N = 139). INT received a wrist-worn monitor (Polar Active) showing daily activity, and CON received identical monitors without feedback. Main outcome was the change from baseline in objectively measured weekly time spent in moderate-to-vigorous PA (MVPA) and sedentary activity (SED), as assessed by generalized estimation equations (GEE). Other lifestyle factors were assessed by a questionnaire at baseline and at 3 months. Weekly physical activity data (>= 4 days with >= 8 h each) were obtained from 72 (53%) and 90 (65%) men in the INT and CON, respectively. Based on GEE, time spent in MVPA increased (p = 0.012) and SED decreased (p = 0.032) in the INT compared with the CON. During the first 7 weeks, the INT spent on average 1 h less sedentary than the CON (t-test, p < 0.05). During the first week, the INT showed 12 minutes more MVPA compared to the CON (t-test, p = 0.034). Based on questionnaire data, the proportion of the most sedentary men decreased in the INT (Wilcoxon test, 28% vs. 10%, p = 0.029), with no change in the CON (20% vs. 19%, p = 0.546). To conclude, a wrist-worn activity monitor providing feedback had a short-term positive effect on PA and SED in young men. TRIAL REGISTRATION: This is a pilot study for a larger randomized controlled trial registered to the clinical trials register NCT01376986. PMID- 26844129 TI - Agreement of objectively measured physical activity and sedentary time in preschool children. AB - OBJECTIVE: To determine the intra-individual agreement for objectively measured physical activity (PA) and sedentary behavior (SED) over two subsequent weeks in preschool children. METHOD: Ninety-one children aged 3 to 5 years (49% boys) from three preschools in Sogn og Fjordane, Norway, provided 14 consecutive days of accelerometer data (Actigraph GT3X +) during the autumn of 2014. Week-by-week reliability was assessed using intraclass correlation (ICC), Bland-Altman plots and 95% limits of agreement for different wear time criteria (>= 6, 8 and 10 h/day and >= 3 and 5 days/week). RESULTS: The week-by-week ICC was >= 0.75 for all variables across all wear criteria applied, except for absolute sedentary time (ICC 0.61-0.81). Using a >= 8 h/day and >= 3 days/week criterion (n = 78), limits of agreement were +/- 209.5 cpm for overall PA, +/- 68.6 min/day for SED, +/- 43.8 min/day for light PA, +/- 20.2 min/day for moderate-to-vigorous PA, and +/- 55.9 min/day for light-to-vigorous PA, equaling 1.0-1.6 standard deviation units. CONCLUSION: Considerable week-by-week variability was found for all variables. Researchers need to be aware of substantial intra-individual variability in accelerometer-measurements and take necessary actions according to the hypothesis under study, as noise in any measurement will preclude researchers' ability to arrive at valid conclusions in epidemiology. PMID- 26844130 TI - Effect of mobile reminders on screening yield during opportunistic screening for type 2 diabetes mellitus in a primary health care setting: A randomized trial. AB - Objective. We wanted to study whether mobile reminders increased follow-up for definitive tests resulting in higher screening yield during opportunistic screening for diabetes. Methods. This was a facility-based parallel randomized controlled trial during routine outpatient department hours in a primary health care setting in Puducherry, India (2014). We offered random blood glucose testing to non-pregnant non-diabetes adults with age >30 years (667 total, 390 consented); eligible outpatients (random blood glucose >= 6.1 mmol/l, n = 268) were requested to follow-up for definitive tests (fasting and postprandial blood glucose). Eligible outpatients either received (intervention arm, n = 133) or did not receive mobile reminder (control arm, n = 135) to follow-up for definitive tests. We measured capillary blood glucose using a glucometer to make epidemiological diagnosis of diabetes. The trial was registered with Clinical Trial Registry of India (CTRI/2014/10/005138). Results. 85.7% of outpatients in intervention arm returned for definitive test when compared to 53.3% in control arm [Relative Risk = 1.61, (0.95 Confidence Interval - 1.35, 1.91)]. Screening yield in intervention and control arm was 18.6% and 10.2% respectively. Etiologic fraction was 45.2% and number needed to screen was 11.9. Conclusion. In countries like India, which is emerging as the diabetes capital of the world, considering the wide prevalent use of mobile phones, and real life resource limited settings in which this study was carried out, mobile reminders during opportunistic screening in primary health care setting improve screening yield of diabetes. PMID- 26844131 TI - How much will we pay to increase steps per day? Examining the cost-effectiveness of a pedometer-based lifestyle program in primary care. AB - We previously demonstrated the Healthy Eating and Active Living for Diabetes (HEALD) intervention was effective for increasing daily steps. Here, we consider the cost-effectiveness of the HEALD intervention implemented in primary care. HEALD was a pedometer-based program for adults with type-2 diabetes in Alberta, Canada completed between January 2010 and September 2012. The main outcome was the change in pedometer-determined steps/day compared to usual care. We estimated total costs per participant for HEALD, and total costs of health care utilization through linkage with administrative health databases. An incremental cost effectiveness ratio (ICER) was estimated with regression models for differences in costs and effects between study groups. The HEALD intervention cost $340 per participant over the 6-month follow-up. The difference in total costs (intervention plus health care utilization) was $102 greater per HEALD participant compared to usual care. The intervention group increased their physical activity by 918 steps/day [95% CI 116, 1666] compared to usual care. The resulting ICER was $111 per 1000 steps/day, less than an estimated cost effectiveness threshold. Increasing daily steps through an Exercise Specialist led group program in primary care may be a cost-effective approach towards improving daily physical activity among adults with type-2 diabetes. Alternative delivery strategies may be considered to improve the affordability of this model for primary care. PMID- 26844132 TI - Efficacy and causal mechanism of an online social media intervention to increase physical activity: Results of a randomized controlled trial. AB - OBJECTIVE: To identify what features of social media - promotional messaging or peer networks - can increase physical activity. METHOD: A 13-week social media based exercise program was conducted at a large Northeastern university in Philadelphia, PA. In a randomized controlled trial, 217 graduate students from the University were randomized to three conditions: a control condition with a basic online program for enrolling in weekly exercise classes led by instructors of the University for 13 weeks, a media condition that supplemented the basic program with weekly online promotional media messages that encourage physical activity, and a social condition that replaced the media content with an online network of four to six anonymous peers composed of other participants of the program, in which each participant was able to see their peers' progress in enrolling in classes. The primary outcome was the number of enrollments in exercise classes, and the secondary outcomes were self-reported physical activities. Data were collected in 2014. RESULTS: Participants enrolled in 5.5 classes on average. Compared with enrollment in the control condition (mean = 4.5), promotional messages moderately increased enrollment (mean = 5.7, p = 0.08), while anonymous social networks significantly increased enrollment (mean = 6.3, p = 0.02). By the end of the program, participants in the social condition reported exercising moderately for an additional 1.6 days each week compared with the baseline, which was significantly more than an additional 0.8 days in the control condition. CONCLUSION: Social influence from anonymous online peers was more successful than promotional messages for improving physical activity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02267369. PMID- 26844133 TI - Community-identified strategies to increase physical activity during elementary school recess on an American Indian reservation: A pilot study. AB - The aim of this study was to determine the effect of an 8-week recess intervention on physical activity levels in children attending elementary school on an American Indian reservation during fall 2013. Physical activity was measured with direct observation in three zones on the playground. Lines were painted on existing pavement in zone 1. Zone 2 had permanent playground equipment and was unchanged. Zone 3 contained fields where bi-weekly facilitators led activities and provided equipment. Pre- to post-changes during recess in sedentary, moderate physical activity, moderate-to-vigorous, and vigorous physical activities were compared within zones. Females physical activity increased in Zone 1 (moderate: 100% increase; moderate-to-vigorous: 83%; vigorous: 74%, p < 0.01 for all) and Zone 3 (moderate: 54% increase, p < 0.01; moderate-to-vigorous: 48%, p < 0.01; vigorous: 40%, p < 0.05). Male sedentary activity decreased in Zone 2 (161%, p < 0.01). Physical activity changes in Zone 3 were not dependent upon the presence of a facilitator. Simple and low-cost strategies were effective at increasing recess physical activity in females. The findings also suggest that providing children games that are led by a facilitator is not necessary to increase physical activity as long as proper equipment is provided. PMID- 26844134 TI - Navigating to health: Evaluation of a community health center patient navigation program. AB - Patient Navigators are trained, lay health care workers who guide patients in overcoming barriers to health care access and utilization. Little evidence exists regarding reach and impact of Patient Navigators for chronic disease management. This study evaluated a Patient Navigator program aimed at optimizing health care utilization among ethnically diverse patients with diabetes and/or hypertension at a community health center (CHC). Trained Patient Navigators contacted eligible patients who had not seen a primary care provider (PCP) for >= 6 months. Outcomes included number of patients reached by Patient Navigators and seen by PCPs after Patient Navigator contact. Distributions and frequencies of outcomes pre- and post-call were compared. A total of 215 patients had >= 1 call attempt from Patient Navigators. Of these, 74 were additionally contacted via mailed letters or at the time of a CHC visit. Among the 45 patients reached, 77.8% scheduled an appointment through the Patient Navigator. These patients had higher rates of PCP visits 6 months post-call (90%) than those not reached (42.2%) (p < 0.0001). Findings emphasize the value of direct telephone contact in patient health care re-engagement and may inform the development of future Patient Navigator programs to improve reach and effectiveness. PMID- 26844135 TI - Acceptability of mobile health interventions to reduce inactivity-related health risk in central Pennsylvania adults. AB - Insufficient physical activity and excessive sedentary behavior elevate health risk. Mobile applications (apps) provide one mode for delivering interventions to modify these behaviors and reduce health risk. The purpose of this study was to characterize the need for and acceptability of health behavior interventions among rural adults and evaluate the interest in and the value of app-based interventions in this population. Central Pennsylvania adults with smartphones (N = 258) completed a brief web survey in October-November 2012. Most adults report one or both inactivity-related behavioral risk factors, would use a free app to modify those risk behaviors, and would pay a small amount for that app. Low-cost, efficacious apps to increase physical activity or reduce sedentary behavior should be promoted in public health practice. User experience should be at the forefront of this process to increase value and minimize burden in the service of long-term engagement, behavior change, and health risk reduction. PMID- 26844136 TI - Playing Active Video Games may not develop movement skills: An intervention trial. AB - BACKGROUND: To investigate the impact of playing sports Active Video Games on children's actual and perceived object control skills. METHODS: Intervention children played Active Video Games for 6 weeks (1 h/week) in 2012. The Test of Gross Motor Development-2 assessed object control skill. The Pictorial Scale of Perceived Movement Skill Competence assessed perceived object control skill. Repeated measurements of object control and perceived object control were analysed for the whole sample, using linear mixed models, which included fixed effects for group (intervention or control) and time (pre and post) and their interaction. The first model adjusted for sex only and the second model also adjusted for age, and prior ball sports experience (yes/no). Seven mixed-gender focus discussions were conducted with intervention children after programme completion. RESULTS: Ninety-five Australian children (55% girls; 43% intervention group) aged 4 to 8 years (M 6.2, SD 0.95) participated. Object control skill improved over time (p = 0.006) but there was no significant difference (p = 0.913) between groups in improvement (predicted means: control 31.80 to 33.53, SED = 0.748; intervention 30.33 to 31.83, SED = 0.835). A similar result held for the second model. Similarly the intervention did not change perceived object control in Model 1 (predicted means: control: 19.08 to 18.68, SED = 0.362; intervention 18.67 to 18.88, SED = 0.406) or Model 2. Children found the intervention enjoyable, but most did not perceive direct equivalence between Active Video Games and 'real life' activities. CONCLUSIONS: Whilst Active Video Game play may help introduce children to sport, this amount of time playing is unlikely to build skill. PMID- 26844137 TI - What distinguishes successful from unsuccessful tobacco smoking cessation? Data from a study of young adults (TEMPO). AB - INTRODUCTION: Smoking prevalence rates among young people are high in many countries. Although attempts to quit smoking increasingly occur in young adulthood, many former smokers relapse. We compared individuals who successfully quit smoking from those who relapsed on socio-demographic, psychological and health factors. METHODS: Data come from telephone interviews conducted in 2011 with participants of the TEMPO community-based study (ages 18-37 years, France). To study the likelihood of successful cessation vs. smoking relapse, we restricted the study sample to current or former smokers (n = 600) and conducted multinomial logistic regression analyses. RESULTS: 43% of participants were current smokers who never quit for an extended period and, 33% former smokers and 24% current smokers who relapsed after extended cessation. In multivariate analyses female sex, parental status and illegal drug use were associated with both successful and unsuccessful smoking cessation. Factors specifically associated with a low probability of smoking cessation were job strain and symptoms of hyperactivity/inattention, while occupational grade was associated with smoking relapse. CONCLUSIONS: Work and family circumstances, co-occurring substance use and psychological difficulties may influence smoking cessation in young adults. These characteristics should be considered by individual and collective interventions aiming to help young smokers quit successfully. PMID- 26844138 TI - Community food environment measures in the Alabama Black Belt: Implications for cancer risk reduction. AB - In-store measures were utilized to evaluate the availability of healthy food choices and nutrition/health promotion messages for cancer risk reduction in the selected Alabama Black Belt counties/cities. Sixty one retail food outlets (RFOs) were audited in 12 Alabama Black Belt cities. Store types included convenience stores (49.2%), restaurants (19.7%), fast food restaurants (16.4%), small supermarkets (8.2%), and large supermarket and farmers' markets (3.3 %), respectively. Although there were low numbers of farmers' markets/street stands and large supermarkets, these had significantly (p < 0.0001) higher health scores than the other store types. A few health promotion messages were highly visible or obscurely positioned in some RFOs. The Alabama Black Belt food environment had limited opportunities for healthy food choices. PMID- 26844139 TI - Socioeconomic inequalities of cardiovascular risk factors among manufacturing employees in the Republic of Ireland: A cross-sectional study. AB - OBJECTIVES: To explore socioeconomic differences in four cardiovascular disease risk factors (overweight/obesity, smoking, hypertension, height) among manufacturing employees in the Republic of Ireland (ROI). METHODS: Cross sectional analysis of 850 manufacturing employees aged 18-64 years. Education and job position served as socioeconomic indicators. Group-specific differences in prevalence were assessed with the Chi-squared test. Multivariate regression models were explored if education and job position were independent predictors of the CVD risk factors. Cochran-Armitage test for trend was used to assess the presence of a social gradient. RESULTS: A social gradient was found across educational levels for smoking and height. Employees with the highest education were less likely to smoke compared to the least educated employees (OR 0.2, [95% CI 0.1-0.4]; p < 0.001). Lower educational attainment was associated with a reduction in mean height. Non-linear differences were found in both educational level and job position for obesity/overweight. Managers were more than twice as likely to be overweight or obese relative to those employees in the lowest job position (OR 2.4 [95% CI 1.3-4.6]; p = 0.008). CONCLUSION: Socioeconomic inequalities in height, smoking and overweight/obesity were highlighted within a sub-section of the working population in ROI. PMID- 26844140 TI - Neighborhood walkability, fear and risk of falling and response to walking promotion: The Easy Steps to Health 12-month randomized controlled trial. AB - In older adults the relationships between health, fall-related risk factors, perceived neighborhood walkability, walking behavior and intervention impacts are poorly understood. To determine whether: i) health and fall-related risk factors were associated with perceptions of neighborhood walkability; ii) perceived environmental attributes, and fall-related risk factors predicted change in walking behavior at 12 months; and iii) perceived environmental attributes and fall-related risk factors moderated the effect of a self-paced walking program on walking behavior. Randomized trial on walking and falls conducted between 2009 and 2012 involving 315 community-dwelling inactive adults >= 65 years living in Sydney, Australia. Measures were: mobility status, fall history, injurious fall and fear of falling (i.e., fall-related risk factors), health status, walking self-efficacy and 11 items from the neighborhood walkability scale and planned walking >= 150 min/week at 12 months. Participants with poorer mobility, fear of falling, and poor health perceived their surroundings as less walkable. Walking at 12 months was significantly greater in "less greenery" (AOR = 3.3, 95% CI: 1.11-9.98) and "high traffic" (AOR = 1.98, 95% CI: 1.00-3.91) neighborhoods. The intervention had greater effects in neighborhoods perceived to have poorer pedestrian infrastructure (p for interaction = 0.036). Low perceived walkability was shaped by health status and did not appear to be a barrier to walking behavior. There appears to be a greater impact of, and thus, need for, interventions to encourage walking in environments perceived not to have supportive walking infrastructure. Future studies on built environments and walking should gather information on fall-related risk factors to better understand how these characteristics interact. PMID- 26844141 TI - Adherence to cervical cancer screening varies by human papillomavirus vaccination status in a high-risk population. AB - Cervical cancer screening has reduced the incidence of cervical cancer over the past 75 years. The primary aim of this study was to determine if women receiving GardasilTM (HPV4 vaccine) participated in future cervical cancer screening at the same rate as that observed for unvaccinated women matched on birth year and health care campus. This is a retrospective cohort study of subjects selected from 27,786 females born from 1980 to 1992 who received health care in the Truman Medical Center safety net health system in Kansas City Missouri, USA. 1154 women 14-26 years old who received at least one dose of HPV4 vaccine between 2006 and 2009 were chosen at random from the vaccine records. 1154 randomly chosen unvaccinated women were age and health campus matched to the vaccinated women and all were followed until July 1, 2013. Women who were screened after 21 years and received three vaccine doses before 21 years, had the lowest screening rate of 24%. Their only predictive factor for screening, compared to the unvaccinated, was being closer to 21 years than 14 years at vaccination (aOR = 1.71 95% CI: 1.45, 2.00). Women vaccinated with three doses and screened at or after 21 years had the highest screening rate of 84% predicting a six-fold increase in screening participation over no vaccine received (aOR = 5.94 95% CI: 3.77, 9.35). Our results suggest that women who receive HPV4 vaccination closer to 21 years, not 14, are more likely to participate in cervical cancer screening in an underserved US population. PMID- 26844142 TI - Readiness of primary care clinicians to implement lung cancer screening programs. AB - We examined the readiness of primary care clinicians to implement lung cancer screening programs in their practice settings in light of recent policy changes in the U.S. Attendees of two large continuing medical education events in Texas held in October and November of 2014 completed surveys about their current lung cancer screening practices and implementation needs. Surveys were completed by 350 participants (57.2% of registered attendees). Although 89.5% of participants routinely screened their patients for tobacco use, only 10.1% had a formal lung cancer screening program in their practice. More than half (56.0%) planned to refer eligible patients for lung cancer screening, 35.6% were not sure, and 8.3% did not plan to refer. Priority areas for implementing lung cancer screening programs in their settings included 1) greater clarity about coverage by private insurance and Medicare, 2) information about available screening centers offering low-dose computed tomography, 3) patient education and shared decision-making tools, 4) implementation toolkits and training for clinic staff, 5) integrating screening programs in electronic health records, and 6) more clarity about clinical guidelines. Practical needs related to identifying eligible patients, referral to screening centers, and tools for shared decision-making must be addressed before lung cancer screening can be implemented on a national scale. PMID- 26844143 TI - Physical activity and sedentary behavior among children and adolescents living in an area affected by the 2011 Great East Japan earthquake and tsunami for 3 years. AB - The purpose of this study is to examine the change in physical activity levels among children and adolescents living in the area affected by the 2011 earthquake and tsunami for 3 years immediately following the disaster. Children and adolescents graded four to nine and attending school in the Pacific coastal area of northern Japan were included in a total of four serial prevalence investigations: the first at 6 months after the earthquake/tsunami (I, n = 434) and additional surveys at 1 year (II, n = 437), 2 years (III, n = 401), and 3 years (IV, n = 365) after the earthquake. Students were also required to undergo assessment of their accelerometer-determined daily steps and sedentary time using a self-administrated questionnaire. Accelerometer-determined median daily steps of children and adolescents were significantly different (p < 0.05) on both weekdays and weekends over 3 years. The median daily steps of children of both genders on weekdays and those of girls on weekends at period IV were significantly lower than those at period I. In addition, the median daily steps of adolescents on weekdays among girls and weekends among boys at period IV were significantly lower than those at period I. It appears that children and adolescents who survive the earthquake and tsunami experience a decrease in physical activity levels. Future research should elucidate longitudinal demographic and sociocultural factors that contribute to changes in physical activity levels among children and adolescents living in the areas affected by these disasters. PMID- 26844144 TI - Improvement in the estimation of cardiovascular risk by carotid intima-medial thickness: A report from the Dublin Cardiohealth station study. AB - BACKGROUND: The 5th Joint Task Force European guidelines on cardiovascular disease (CVD) prevention recommend the measurement of carotid intima-media thickness (CIMT) in asymptomatic individuals at moderate risk (Class IIa). We aimed to evaluate the ability of CIMT to further risk stratify patients. DESIGN: Cross-sectional study. METHODS: Patients aged over 18 years free of known CVD at moderate, high, or very high risk of CVD were included. The Panasonic Cardiohealth station, a semi-automated ultrasound system, was used to detect carotid plaque and measure CIMT. Elevated CIMT was defined as =/> 0.9 mm. We analyzed the percentage of those at moderate risk reclassified after addition of CIMT. RESULTS: Two hundred patients were included (55% women, mean age 57 years, 12% diabetic); 64%, 23% and 13% were classified as moderate, high, and very high risk, respectively. Across these risk categories, 17%, 33%, and 46% had elevated IMT, p for trend < 0.001. With the addition of CIMT, 13.9% (95% CI: 5.7% to 22.1%) of women and 20.4% (95% CI: 8.7% to 32.1%) of men initially moderate risk were reclassified. CONCLUSIONS: CIMT measurement reclassifies a considerable percentage of those at moderate risk based on traditional risk factors alone. PMID- 26844146 TI - Effect of telephone follow-up on retention and balance in an alcohol intervention trial. AB - OBJECTIVES: Telephone follow-up is not currently recommended as a strategy to improve retention in randomized trials. The aims of this study were to estimate the effect of telephone follow-up on retention, identify participant characteristics predictive of questionnaire completion during or after telephone follow-up, and estimate the effect of including participants who provided follow up data during or after telephone follow-up on balance between randomly allocated groups in a trial estimating the effect of electronic alcohol screening and brief intervention on alcohol consumption in hospital outpatients with hazardous or harmful drinking. METHOD: Trial participants were followed up 6 months after randomization (June-December 2013) using e-mails containing a hyperlink to a web based questionnaire when possible and by post otherwise. Telephone follow-up was attempted after two written reminders and participants were invited to complete the questionnaire by telephone when contact was made. RESULTS: Retention before telephone follow-up was 62.1% (520/837) and 82.8% (693/837) afterward: an increase of 20.7% (173/837). Therefore, 55% (95% CI 49%-60%) of the 317 participants who had not responded after two written reminders responded during or after the follow-up telephone call. Age < 55 years, a higher AUDIT-C score and provision of a mobile/cell phone number were predictive of questionnaire completion during or after telephone follow-up. Balance between randomly allocated groups was present before and after inclusion of participants who completed the questionnaire during or after telephone follow-up. CONCLUSION: Telephone follow-up improved retention in this randomized trial without affecting balance between the randomly allocated groups. PMID- 26844147 TI - Food and beverage promotions in Vancouver schools: A study of the prevalence and characteristics of in-school advertising, messaging, and signage. AB - The purpose of this study was to provide a descriptive profile of food-related advertising, messaging, and signage in Vancouver schools and to examine differences in the prevalence and characteristics of promotions between elementary and secondary schools. All food-related promotions were photographed in 23 diverse Vancouver public schools between November 2012 and April 2013. Key attributes, including the location, size, and main purpose of each promotion, as well as the type of food and/or beverage advertised and compliance with provincial school nutrition guidelines, were coded. Descriptive statistics assessed the prevalence and characteristics of promotions. Cross-tabulations examined whether the promotional landscape differed between elementary and secondary schools. All secondary and 80% of elementary schools contained food or beverage promotions (median = 17, range = 0-57 promotions per school). Of the 493 promotions documented, approximately 25% depicted "choose least" or "not recommended" items, prohibited for sale by provincial school nutrition guidelines. Nearly 1/3 of promotions advertised commercial items (e.g., brand name beverages such as Pepsi), in violation of the Board of Education's advertising policies and only 13% conveyed nutrition education messages. Close to half of all promotions were created by students for class projects, many of which marketed minimally nutritious items. In Vancouver schools, food-related promotions are common and are more prevalent in secondary than elementary schools. Students are regularly exposed to messaging for nutritionally poor items that are not in compliance with provincial school nutrition guidelines and which violate school board advertising policies. Stronger oversight of food-related promotional materials is needed to ensure that schools provide health promoting food environments. PMID- 26844145 TI - From built environment to health inequalities: An explanatory framework based on evidence. AB - OBJECTIVE: The Health in All Policies strategy aims to engage every policy domain in health promotion. The more socially disadvantaged groups are usually more affected by potential negative impacts of policies if they are not health oriented. The built environment represents an important policy domain and, apart from its housing component, its impact on health inequalities is seldom assessed. METHODS: A scoping review of evidence on the built environment and its health equity impact was carried out, searching both urban and medical literature since 2000 analysing socio-economic inequalities in relation to different components of the built environment. RESULTS: The proposed explanatory framework assumes that key features of built environment (identified as density, functional mix and public spaces and services), may influence individual health through their impact on both natural environment and social context, as well as behaviours, and that these effects may be unequally distributed according to the social position of individuals. CONCLUSION: In general, the expected links proposed by the framework are well documented in the literature; however, evidence of their impact on health inequalities remains uncertain due to confounding factors, heterogeneity in study design, and difficulty to generalize evidence that is still very embedded to local contexts. PMID- 26844148 TI - Profiles of resistance training behavior and sedentary time among older adults: Associations with health-related quality of life and psychosocial health. AB - BACKGROUND: The primary objective of this study was to gain a better understanding of the associations of health-related quality of life (HRQoL) and psychosocial factors (e.g., satisfaction with life, level of self-esteem, anxiety, depression) with resistance training and sedentary behavior profiles. METHODS: For this cross-sectional study, 358 older adults (>= 55 years of age) across Alberta, Canada, completed self-reported measures of resistance training behavior, sedentary time, HRQoL, and psychosocial health (e.g., depression, anxiety, self-esteem, satisfaction with life). Participants were placed into one of four profiles with respect to their sedentary and resistance training behaviors. Data were collected in Alberta, Canada between August 2013 and January 2014. RESULTS: Pairwise comparisons indicated that those in the low SED/low RT group had a higher mental health composite (MHC) score compared to those in the high SED/low RT group (M diff = 3.9, p = 0.008). Compared to those in the high SED/low RT group, those in the low SED/high RT groups had significantly higher MHC scores (M diff = 4.8, p < 0.001). Those in the low SED/high RT group reported significantly higher physical health composite scores (PHC) (M diff = 3.7, p = 0.019), compared to the high SED/low RT group. Lower depression symptom scores were observed in the low SED/high RT groups compared to the high SED/low RT group, (M diff = - 0.60, p < 0.001). CONCLUSION: Resistance training, regardless of sedentary time, was significantly associated with HRQoL and psychosocial health. PMID- 26844149 TI - Does proximity to physical activity infrastructures predict maintenance of organized and unorganized physical activities in youth? AB - Physical activity (PA) infrastructures can provide youth chances to engage in PA. As determinants of organized and unorganized PA (OPA and UPA) may differ, we investigated if proximity to PA infrastructures (proximity) was associated with maintenance of OPA and UPA over 3 years. Youth from New Brunswick, Canada (n = 187; 10-12 years at baseline) reported participation in OPA and UPA every 4 months from 2011 to 2014 as part of the MATCH study. Proximity data were drawn from parent's questionnaires. Proximity scores were divided into tertiles. Kaplan Meier and Cox proportional hazard models were used to assess associations between proximity and maintenance of OPA and UPA. There were no crude or adjusted differences in average maintenance of participation in OPA [mean number of survey cycle participation (95%CI) was 6.6 (5.7-7.5), 6.3 (5.5-7.1), and 5.8 (5.1-6.6)] or UPA [6.8 (6.2-7.4), 5.9 (5.3-6.5), and 6.6 (5.9-7.3)] across low, moderate, and high tertiles of proximity, respectively. Findings suggest that proximity does not affect maintenance of participation in OPA or UPA during adolescence. Other environmental aspects may have a greater effect. Further research is needed before conclusions can be made. PMID- 26844150 TI - The association between cardiorespiratory fitness and abdominal adiposity in postmenopausal, physically inactive South Asian women. AB - In South Asians, a unique obesity phenotype of high abdominal fat is associated with increased cardiovascular risk. Low cardiorespiratory fitness (CRF) is associated with abdominal fat and an increased risk of cardiovascular disease. The purpose of this paper is to determine whether CRF as assessed by VO2 peak, in post-menopausal South Asian women, was associated with body fat distribution and abdominal fat. Physically inactive post-menopausal South Asian women (n = 55) from the Greater Vancouver area were recruited and assessed from January to August 2014. At baseline, VO2 peak was measured with the Bruce Protocol, abdominal fat with CT imaging, and body composition with dual energy X-ray absorptiometry. ANOVA was used to assess differences in subcutaneous abdominal adipose tissue (SAAT), visceral adipose tissue (VAT) and total abdominal adipose tissue (TAAT) between tertiles of CRF. Bivariate correlation and multiple linear regression analyses explored the association between VO2 peak with SAAT, VAT, TAAT and body composition. Models were further adjusted for body fat and body mass index (BMI). Compared to women in the lowest tertile of VO2 peak (13.8-21.8 mL/kg/min), women in the highest tertile (25.0-27.7 mL/kg/min) had significantly lower waist circumference, BMI, total body fat, body fat percentage, lean mass, SAAT, VAT and TAAT (p < 0.05). We found VO2 peak to be negatively associated with SAAT, VAT and TAAT, independent of age and body fatness but not independent of BMI. Further research is necessary to assess whether exercise and therefore improvements in CRF would alter SAAT, VAT and TAAT in post-menopausal South Asian women. PMID- 26844151 TI - Non-therapist identification of falling hazards in older adult homes using digital photography. AB - Evaluation and removal of home hazards is an invaluable method for preventing in home falls and preserving independent living. Current processes for conducting home hazard assessments are impractical from a whole population standpoint given the substantial resources required for implementation. Digital photography offers an opportunity to remotely evaluate an environment for falling hazards. However, reliability of this method has only been tested under the direction of skilled therapists. Ten community dwelling adults over the age of 65 were recruited from local primary care practices between July, 2009 and February, 2010. In-home (IH) assessments were completed immediately after a photographer, blinded to the assessment form, took digital photographs (DP) of the participant home. A different non-therapist assessor then reviewed the photographs and completed a second assessment of the home. Kappa statistic was used to analyze the reliability between the two independent assessments. Home assessments completed by a non-therapist using digital photographs had a substantial agreement (Kappa = 0.61, p < 0.001) with in-home assessments completed by another non-therapist. Additionally, the DP assessments agreed with the IH assessments on the presence or absence of items 96.8% of the time. This study showed that non-therapists can reliably conduct home hazard evaluations using digital photographs. PMID- 26844152 TI - High mercury seafood consumption associated with fatigue at specialty medical clinics on Long Island, NY. AB - We investigated the association between seafood consumption and symptoms related to potential mercury toxicity in patients presenting to specialty medical clinics at Stony Brook Medical Center on Long Island, New York. We surveyed 118 patients from April-August 2012 about their seafood consumption patterns, specifically how frequently they were eating each type of fish, to assess mercury exposure. We also asked about symptoms associated with mercury toxicity including depression, fatigue, balance difficulties, or tingling around the mouth. Of the 118 adults surveyed, 14 consumed high mercury seafood (tuna steak, marlin, swordfish, or shark) at least weekly. This group was more likely to suffer from fatigue than other patients (p = 0.02). Logistic regression confirmed this association of fatigue with frequent high mercury fish consumption in both unadjusted analysis (OR = 5.53; 95% CI: 1.40-21.90) and analysis adjusted for age, race, sex, income, and clinic type (OR = 7.89; 95% CI: 1.63-38.15). No associations were observed between fish intake and depression, balance difficulties, or tingling around the mouth. Findings suggest that fatigue may be associated with eating high mercury fish but sample size is small. Larger studies are needed to determine whether fish intake patterns or blood mercury tests warrant consideration as part of the clinical work-up in coastal regions. PMID- 26844153 TI - Household characteristics and influenza vaccination uptake in the community dwelling elderly: a cross-sectional study. AB - Elderly people are at higher risk of influenza diseases. The morbidity benefit of vaccination is often offset by its low and variable coverage in elderly people in the community. To assess household and individual factors associated with influenza vaccination uptake in the community-dwelling elderly of age >= 65, data from a cross-sectional Thematic Household Survey conducted in 2011/12 in Hong Kong were analysed, using vaccination in the past 12 months as the outcome variable. Households comprising an elderly person living with non-elderly member(s) of age <= 64 were also evaluated. Data fields included socio demographics, household structures, health status, eligibility to financial subsidy, and subscription to health insurance. The influenza vaccination rate was 27% in 4204 elderly persons from 3224 households. Being male, being economically active, attaining primary education, having smoking behaviours were negatively associated with vaccination, while chronic illness and age >= 70 were positively associated factors. Elderly people living alone gave a variable rate of vaccination ranging from 16.4% in males of age 65-69 to 36.3% in females >= 70. Household size per se was not associated with vaccination, but a positive correlation could be seen if the household was composed of vaccinated non-elderly member(s). Influenza vaccination uptake in the community-dwelling elderly is dependent on both individual and household characteristics, the latter including the influence of vaccinated non-elderly member(s). The low vaccination coverage of "younger" (age 65-69) elderly men living alone is particularly worrisome. Interventions focusing on vulnerable elderly people and their social networks would be desirable. PMID- 26844154 TI - Now or later? Understanding the etiologic period of suicide. AB - Previous research shows that the announcement of austerity measures leads to an immediate and short-lived increase in behaviour that demonstrates anxiety, stress, frustration and other mental effects. This paper uses evidence from the same natural experiment to study whether, for a given decision to commit suicide (as documented by the overall increase over the study period), suicides follow immediately after the announcement of austerity measures in Greece; or whether this is an effect that matures in peoples' minds before being transformed into action. We use evidence from a natural experiment and follow an econometric approach. Our findings show that, despite an overall sharp increase in suicides over the study period, the increase does not follow immediately in the first few days after each such negative event. This suggests that suicides are not spontaneous. They are rather decisions that take time to mature. This time lag implies that suicides arguably attributed to recessions are, in principle, preventable and underlines the importance of mental health services. PMID- 26844155 TI - Co-occurrence of protective health behaviours and perceived psychosocial job characteristics. AB - Little is known about the association between positive job characteristics of older workers and the co-occurrence of protective health behaviours. This study aims to investigate the association between perceived psychosocial job characteristics and the adoption of protective health behaviours. A population based cross-sectional study was performed on a sample of 1025 males and females (age-range 50-69-years) attending a primary healthcare clinic. Perceived job characteristics (job demands: quantitative and cognitive demands; resources: possibility for development and influence at work) were determined using the Copenhagen Psychosocial Questionnaire. Each scale is presented in tertiles. Protective health behaviours were; consumption of five or more portions of fruit and vegetables a day, moderate alcohol, non/ex-smoker, and high and moderate physical activity. Each participant was scored 0-4 protective health behaviours. The majority of the sample had three protective health behaviours. Higher levels of influence at work and cognitive demands were associated with higher self reported physical activity, but not with any number of protective health behaviours. Conversely, higher quantitative and higher cognitive demands were associated with reporting any number of protective health behaviours or above average number of protective health behaviours respectively. The findings on protective health behaviours were inconsistent in relation to the different measures of perceived psychosocial job characteristics and were largely confined to physical activity and diet. PMID- 26844156 TI - Active living environment assessments in four rural Latino communities. AB - OBJECTIVE: Latinos and rural residents are less active and have a greater prevalence of overweight/obesity compared with their non-Latino white and urban counterparts. The objective of this study was to assess the active living environment in four rural, predominantly Latino communities. METHODS: Assessments were taken using the Rural Active Living Assessment (RALA) in four rural predominantly Latino communities in Central Washington from September-November 2013. Street Segment Assessments of town center, thoroughfare, neighborhood and school zones were assessed for features related to walkability. Physical activity amenities, programs and policies in each town were assessed. Scores were generated for amenities, programs and policies. Data were analyzed with descriptive statistics and logistic regression. RESULTS: A total of 103 segments were assessed. Sidewalks in good condition were present in 32% of segments and shoulders in 44% of segments. Half of street segments were rated as walkable. Parks and playgrounds were available; however, half of these were rated in poor condition. All four districts offered after school physical activity programming but only two had a late bus option. CONCLUSIONS: These four rural towns have some policies, programming and infrastructure in place that support active living. The information from the RALA can be used to inform program and policy development to enhance physical activity in these rural communities. PMID- 26844157 TI - Early motor skill competence as a mediator of child and adult physical activity. AB - OBJECTIVE: In order to effectively promote physical activity (PA) during childhood, and across the lifespan, a better understanding of the role of early motor skill development on child and adult PA is needed. METHODS: Here, we propose a conceptual model delineating the hypothesized influence of motor skill development on child and adult PA, while providing an overview of the current empirical research related to this model. RESULTS: There is consistent and emerging evidence showing that adequate motor skill competence, particularly locomotor and gross motor skills, is associated with increased PA levels during the preschool, child, and adolescent years, with early motor skill development also influencing enjoyment of PA as well as long-term PA and motor skill performance. The physical education setting appears to be a well-suited environment for motor skill development. CONCLUSION: Employing appropriate strategies to target motor skill development across the childhood years is of paramount interest in helping shape children's PA behavior, their experiences related to PA, as well as maintain their PA. PMID- 26844158 TI - Perceived health status associated with transport choice for short distance trips. AB - BACKGROUND: This study examines the association between active transport and perceived general health, perceived psychological wellbeing and a healthy body weight in the Netherlands. METHODS: Data were collected by an online questionnaire (N = 3663) in the Netherlands. Data collection was conducted over a period of one calendar year starting July 2012. Logistic regression analyses were used to investigate the association between choice of transport mode (bicycling vs car use and walking vs car use) and perceived general health, perceived psychological wellbeing and having a healthy weight respectively. The presented OR's may be interpreted as the likelihood of an average person in our dataset to have a better perceived health or body weight when choosing active transport (either bicycling or walking) over using the car for trips up to 7.5 km. RESULTS: Cycling was found to be significantly associated with a better perceived general health (OR = 1.35, 95%CI:1.07-1.70) and having a healthy body weight (OR = 1.52, 95%CI:1.28-1.79), but not with a better perceived psychological wellbeing (OR = 1.12, 95%CI:0.93-1.34). Walking was found to be significantly associated with having a healthy body weight (OR = 1.35, 95%CI:1.09-1.69), but not with a better perceived general (OR = 1.12, 95%CI:0.84-1.51) or psychological wellbeing (OR = 0.85, 95%CI:0.67-1.08). CONCLUSION: Our results suggest that active transport use has been associated with a better perceived general health and a healthy body weight. However, more research is needed to be able to elucidate which factors cause this better health. No associations were observed between transport choice and perceived psychological wellbeing. PMID- 26844159 TI - Accelerometer-measured sedentary time among Hispanic adults: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). AB - Excessive sedentary behavior is associated with negative health outcomes independent of physical activity. Objective estimates of time spent in sedentary behaviors are lacking among adults from diverse Hispanic/Latino backgrounds. The objective of this study was to describe accelerometer-assessed sedentary time in a large, representative sample of Hispanic/Latino adults living in the United States, and compare sedentary estimates by Hispanic/Latino background, sociodemographic characteristics and weight categories. This study utilized baseline data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) that included adults aged 18-74 years from four metropolitan areas (N = 16,415). Measured with the Actical accelerometer over 6 days, 76.9% (n = 12,631) of participants had > 10 h/day and > 3 days of data. Participants spent 11.9 h/day (SD 3.0), or 74% of their monitored time in sedentary behaviors. Adjusting for differences in wear time, adults of Mexican background were the least (11.6 h/day), whereas adults of Dominican background were the most (12.3 h/day), sedentary. Women were more sedentary than men, and older adults were more sedentary than younger adults. Household income was positively associated, whereas employment was negatively associated, with sedentary time. There were no differences in sedentary time by weight categories, marital status, or proxies of acculturation. To reduce sedentariness among these populations, future research should examine how the accumulation of various sedentary behaviors differs by background and region, and which sedentary behaviors are amenable to intervention. PMID- 26844160 TI - Building the field of population health intervention research: The development and use of an initial set of competencies. AB - Population health intervention research (PHIR) is a relatively new research field that studies interventions that can improve health and health equity at a population level. Competencies are one way to give legitimacy and definition to a field. An initial set of PHIR competencies was developed with leadership from a multi-sector group in Canada. This paper describes the development process for these competencies and their possible uses. Methods to develop the competencies included key informant interviews; a targeted review of scientific and gray literature; a 2-round, online adapted Delphi study with a 24-member panel; and a focus group with 9 international PHIR experts. The resulting competencies consist of 25 items grouped into 6 categories. They include principles of good science applicable though not exclusive to PHIR, and more suitable for PHIR teams rather than individuals. This initial set of competencies, released in 2013, may be used to develop graduate student curriculum, recruit trainees and faculty to academic institutions, plan non-degree professional development, and develop job descriptions for PHIR-related research and professional positions. The competencies provide some initial guideposts for the field and will need to be adapted as the PHIR field matures and to meet unique needs of different jurisdictions. PMID- 26844161 TI - Prevalence of substance use and abuse in late childhood and early adolescence: What are the implications? AB - The aim of the present study was to assess the prevalence by gender of substance use and misuse in late childhood and early adolescence. A survey was conducted in 2013-2014 at primary and secondary schools of Padova, Veneto region, North-East Italy, on a sample of 171 pupils in 5th grade and 1325 in 6th to 8th grade. Among the 8th graders, more than one in three males and one in four females had experimented with smoking, and more than half the boys and nearly half the girls had experience of alcohol. In this same age group, almost two in three males and one in three females had used energy drinks, and nearly 5% of the boys had experience of marijuana and/or stimulant drugs. In addition, almost one in four of the male students in 8th grade had experimented with three of these substances. The middle school years should be identified as the first period at risk concerning the use of these drugs. Prevention programs should begin in early adolescence, focusing on delaying the use or abuse of any of the "gateway drugs." PMID- 26844162 TI - Predictors and grade level trends of school day physical activity achievement in low-income children from the U.S. AB - The achievement of recommended levels (>= 30 min/day) of school moderate-to vigorous physical activity (MVPA) is paramount to decrease risk of chronic disease in children from low-income families. The purpose of this study was to examine the predictors and grade-level trends of school day MVPA achievement in low-income children. Data were collected during the Fall of 2014 on 1232 children (Mean age = 8.8 +/- 1.6 years; 625 girls, 607 boys) recruited from three low income schools from the state of Utah in the U.S. Children wore pedometers for one school week and a stratified random subsample (n = 533) also wore accelerometers to record sedentary time and MVPA. Generalized linear mixed models were employed to calculate odds ratios for achieving school MVPA standards (>= 30 min/day) from various predictors and to determine odds of achievement across grade levels, accounting for school and classroom clustering. Odds of meeting MVPA standards were 3 times greater if a student achieved at least 6000 steps during the school day (p < 0.01), and were 55% lower for every 1% increase in sedentary time (p < 0.001). Older children had 26% lower odds of meeting the recommended levels of MVPA compared to children in an immediately younger grade level (p < 0.05). A significant proportion of MVPA variance was explained by classroom and school affiliation (Rho = 0.09 to 0.54, p < 0.001). Daily steps, sedentary times, grade level, and classroom and school affiliation associate with school MVPA achievement in low-income children. PMID- 26844163 TI - Impacts of public transit improvements on ridership, and implications for physical activity, in a low-density Canadian city. AB - Public transit ridership offers valuable opportunities for modest amounts of daily physical activity (PA). Transit is a more feasible option for most Canadian commuters who live too far from work to walk or cycle, yet public transit usage in midsized Canadian cities has historically remained low due to inefficient transit service. The objectives of this longitudinal study were threefold: to assess whether the introduction of express transit service in the low-density city of Kingston, Ontario, has translated to greater transit use among a targeted employee group; to document the characteristics of those employees that have shifted to transit; and to examine the PA levels of employees using transit compared to other commute modes. An online survey was administered in October 2013 and October 2014 to all non-student employees at Queen's University. 1356 employees completed the survey in 2013, and 1123 in 2014; 656 of these employees completed the survey both years, constituting our longitudinal sample. Year-round transit ridership increased from 5.5% in 2013 to 8.5% in 2014 (p < 0.001). Employees who shifted to transit had fewer household-level opportunities to drive to work and more positive attitudes toward transit. Transit commuters accrued an average of 80 minutes/week of commute-related PA, and 50 minutes/week more total PA than those that commuted entirely passively. Kingston Transit's express service has stimulated an increase in transit ridership among one of their target employers, Queen's University. The findings from this study suggest that shifting to transit from entirely passive commuting can generate higher overall PA levels. PMID- 26844164 TI - Determinants of changes in sedentary time and breaks in sedentary time among 9 and 12 year old children. AB - The current study aimed to identify the determinants of objectively measured changes in sedentary time and sedentary fragmentation from age 9- to age 12 years. Data were collected as part of the Gateshead Millennium Birth Cohort study from September 2008 to August 2009 and from January 2012 to November 2012. Participants were 9.3 (+/- 0.4) years at baseline (n = 508) and 12.5 (+/- 0.3) years at follow-up (n = 427). Sedentary behaviour was measured using an ActiGraph GT1M accelerometer. Twenty potential determinants were measured, within a socio ecological model, and tested for their association with changes in sedentary time and the extent to which sedentary behaviour is prolonged or interrupted (fragmentation index). Univariate and multivariate linear regression analyses were conducted. Measurements taken during winter and a greater decrease in moderate-to-vigorous intensity physical activity (MVPA) over time were associated with larger increases in sedentary time (seasonality beta: - 3.03; 95% CI: - 4.52, - 1.54; and change in MVPA beta: - 1.68; 95% CI: - 1.94, - 1.41). Attendance at sport clubs was associated with smaller increases in sedentary time (- 1.99; - 3.44, - 0.54). Girls showed larger decreases in fragmentation index (- 0.52; - 1.01, - 0.02). Interventions aimed at decreasing the decline in MVPA and increasing/maintaining sport club attendance may prevent the rise in sedentary time as children grow older. In addition, winter could be targeted to prevent an increase in sedentary time and reduction in sedentary fragmentation during this season. PMID- 26844165 TI - Colorectal cancer screening at community health centers: A survey of clinicians' attitudes, practices, and perceived barriers. AB - OBJECTIVE: Colorectal cancer (CRC) screening rates remain lower among some racial/ethnic groups and individuals with low income or educational attainment who are often cared for within community health centers (CHCs). We surveyed clinicians in a network of CHCs to understand their attitudes, practice patterns, and perceived barriers to CRC screening. METHODS: A clinician survey was conducted in 2013 within the Community Health Applied Research Network (CHARN). RESULTS: 180 clinicians completed the survey (47.9% response rate). Participants had an average of 11.5 (SD: 9.8) years in practice, 62% were female, and 57% were physicians. The majority of respondents somewhat agreed (30.2%) or strongly agreed (57.5%) that colonoscopy was the best screening test. However, only 15.8% of respondents strongly agreed and 32.2% somewhat agreed that colonoscopy was readily available for their patients. Fecal immunochemical testing (FIT), a type of fecal occult blood test (FOBT), was viewed less favorably; 24.6% rated FIT as very effective. CONCLUSIONS: Although there are no data showing that screening colonoscopy is superior to FIT, CHC clinicians believe colonoscopy is the best CRC screening test for their patients, despite the high prevalence of financial barriers to colonoscopy. These attitudes could be due to lack of knowledge about the evidence supporting long-term benefits of fecal occult blood testing (FOBT), lack of awareness about the improved test characteristics of FIT compared to older guaiac-based FOBT, or the absence of systems to ensure adherence to regular FOBT screening. Interventions to improve CRC screening at CHCs must address clinicians' negative attitudes towards FIT. PMID- 26844166 TI - Randomized controlled trial of a Wellness Action Plan to promote healthy diet and activity in pediatric primary care. AB - INTRODUCTION: Diet and activity counseling is recommended during all well child visits to promote optimal health and prevent childhood obesity. The objective of this study was to determine the effectiveness of a novel Wellness Action Plan aimed at: 1) improving parent recall of diet and activity plans made during routine well child visits 2) increasing adherence with plans, and 3) enhancing parents' identification of their child's weight category. METHODS: Parents of children 2.5 to 14 years (n = 181) seen at a pediatric primary care clinic in Milwaukee, Wisconsin between March and August of 2013 received standard diet and activity counseling from their physician (both control and intervention groups). In addition, parents randomized to the intervention group were asked to complete a Wellness Action Plan, where established diet and activity goals were documented. Parents completed surveys about BMI identification, plan creation, and plan adherence pre visit, post visit, and at 1 and 3 months. RESULTS: Intervention parents were significantly more likely to recall diet (p = 0.003) and activity (p = 0.03) plans at 3 months and were also more likely to report adherence with diet (p = 0.006) and activity (p = 0.08) plans at three months. There was no difference between groups in their ability to correctly identify children's weight categories (p > 0.05). CONCLUSION: The Wellness Action Plan was associated with higher parent diet and activity plan recall and self-reported adherence. The Wellness Action Plan is a potentially important counseling tool that can be used to help parents make lifestyle modifications for their children. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT02185248. PMID- 26844167 TI - Associations between smoking behaviors and financial stress among low-income smokers. AB - OBJECTIVE: Many American households struggle to bring in sufficient income to meet basic needs related to nutrition, housing, and healthcare. Nicotine addiction and consequent expenditures on cigarettes may impose extra financial strain on low-income households. We examine how cigarette use behaviors relate to self-reported financial stress/strain among low-income smokers. METHODS: At baseline in 2011/12, OPT-IN recruited adult smokers age 18-64 from the administrative databases of the state-subsidized Minnesota Health Care Programs (N = 2406). We tested whether nicotine dependency, type of cigarettes used, and smoking intensity were associated with self-reported difficulty affording food, healthcare, housing, and living within one's income. All regression models were adjusted for race, education, income, age, and gender. RESULTS: Difficulty living on one's income (77.4%), paying for healthcare (33.6%), paying for housing (38.4%), and paying for food (40.8%) were common conditions in this population. Time to first cigarette and cigarettes smoked per day predicted financial stress related to affording food, housing, and living within one's income (all p < 0.05). For instance, those whose time to first cigarette was greater than 60 minutes had about half the odds of reporting difficulty paying for housing compared to those who had their first cigarette within five minutes of waking (adjusted odds ratio = 0.55 [95% CI: 0.41, 0.73]). Type of cigarette used was not associated with any type of financial stress/strain. CONCLUSIONS: Smoking and particularly heavy smoking may contribute in an important way to the struggles that low-income households with smokers face in paying for necessities. PMID- 26844168 TI - Physical performance deterioration of temporary housing residents after the Great East Japan Earthquake. AB - Disaster has a negative impact on health conditions, especially on those of temporary housing residents. Health status has a close relationship with physical activity and performance. However, few reports have assessed physical performance among residents living in temporary housing. In this study, we compared physical capabilities between the elderly who evacuated to temporary housing and those who stayed in their own homes after the Great East Japan Earthquake. Subjects were recruited from those over 65 years of age who participated in the medical check ups for temporary housing residents (TH group) or check-ups for residents of downtown areas (control group) in Soma City, Fukushima, in 2012. The subjects underwent grip strength, one-leg standing (OLS), and timed up and go tests (TUG). In total, 1890 participants were recruited. The TH group showed significantly stronger grip strength than that of the control group. On the other hand, the TH group showed weaker standing stability, according to decreased OLS and increased TUG scores. We revealed that standing stability was impaired among elderly temporary housing residents 1.5 years after the disaster. Disaster responders should take into account the health risks associated with living in temporary housing. PMID- 26844169 TI - Occupational exposure to asbestos and cardiovascular related diseases: A meta analysis. AB - Asbestos has become one of the leading causes of death among occupational workers in the world. The association between asbestos and cardiovascular disease is less reported. We performed a meta-analysis to quantify the association between asbestos exposure and the mortality of cardiovascular related diseases. We performed a systematic review in the PubMed database before December 2014. All cohort studies citing the standardized mortality ratio (SMR) of cardiovascular related diseases in workers exposed to asbestos were collected. We then calculated the pooled standardized mortality ratios of such diseases. Sixteen studies were included. The combined results from all studies indicated the pooled SMR estimate for cardiovascular related diseases was 1.11 (95% CI, 1.01-1.22). This meta-analysis showed that asbestos exposure significantly increased the risk of cardiovascular related diseases in exposed workers. PMID- 26844170 TI - Engagement in muscular strengthening activities is associated with better sleep. AB - Few studies have examined whether engagement in muscular strengthening activities is associated with sleep duration, which was the purpose of this study. Data from the population-based 2005-2006 National Health and Nutrition Examination Survey were used, which included an analytic sample of 4386 adults (20-85 yrs). Sleep duration and engagement in muscle strengthening activities was self-reported. After adjustments (including aerobic-based physical activity), those engaging in muscular strength activities, compared to those not engaging in muscular strengthening activities, had an 19% increased odds of meeting sleep guidelines (7-8 h/night) (Odds Ratio = 1.19, 95% Confidence Interval: 1.01-1.38, P = 0.04). Promotion of muscular strengthening activities by clinicians should occur not only for improvements in other aspects of health (e.g., cardiovascular benefits), but also to help facilitate optimal sleep duration. PMID- 26844171 TI - Insights from an observational assessment of park-based physical activity in Nanchang, China. AB - Internationally, parks have been shown to be an important community asset for physical activity (PA), but little is known about the relationship between park usage and physical activity in China. The purpose of this study was to determine the association between park user characteristics and PA in Nanchang, China. In June 2014, 75,678 people were observed in eight parks over 12 days using SOPARC, a validated systematic observation tool. A logistic regression analysis was used to determine the association between PA and park user characteristics. Most park users were older adults (53.5%) or adults (34.6%). Overall, 55% of park users engaged in moderate-to-vigorous physical activity (MVPA). Fewer women were observed in parks than men, but were 66% more likely to be engaged in MVPA than men. Park users were more likely to be observed in MVPA between 6-9 am and when the temperature was below 30 degrees C. Chinese park users were more active (55%) than US studies in Tampa (30%), Chicago (49%), and Los Angeles (34%). More research is necessary to identify features of parks that are associated with greater PA so that effective interventions can be developed to promote active park use in Chinese citizens. PMID- 26844172 TI - Better movers and thinkers (BMT): A quasi-experimental study into the impact of physical education on children's cognition-A study protocol. AB - This study will extend on a pilot study and will evaluate the impact of a novel approach to PE, Better Movers and Thinkers (BMT), on students' cognition, physical activity habits, and gross motor coordination (GMC). The study will involve six mainstream state schools with students aged 9-11 years. Three schools will be allocated as the intervention condition and three as the control condition. The design of the study is a 16-week intervention with pre-, post- and 6 month follow-up measurements taken using the 'Cognitive Assessment System (CAS)' GMC tests, and the 'Physical Activity Habits Questionnaire for Children (PAQ-C).' Qualitative data will be gathered using student focus groups and class teacher interviews in each of the six schools. ANCOVA will be used to evaluate any effect of intervention comparing pre-test scores with post-test scores and then pre-test scores with 6 month follow-up scores. Qualitative data will be analysed through an iterative process using grounded theory. This protocol provides the details of the rationale and design of the study and details of the intervention, outcome measures, and the recruitment process. The study will address gaps within current research by evaluating if a change of approach in the delivery of PE within schools has an effect on children's cognition, PA habits, and GMC within a Scottish setting. PMID- 26844174 TI - Joint associations of objectively-measured sedentary behavior and physical activity with health-related quality of life. AB - No studies, to my knowledge, have examined the joint effects of physical activity and sedentary behavior on health-related quality of life (HRQOL), which was the purpose of this study. Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used (N = 5,536). Moderate-to-vigorous physical activity (MVPA) and sedentary behavior were assessed using an ActiGraph 7164 accelerometer, with HRQOL assessed using the Centers for Disease Control and Prevention 4-item HRQOL index. MVPA (betaadjusted = - 0.01; 95% CI: - 0.01 to - 0.004; P < 0.001), but not sedentary behavior (betaadjusted = - 0.0003; 95% CI: - 0.001-0.0001; P = 0.37), was associated with HRQOL. MVPA was associated with HRQOL among those above the median (>= 487.5 min/day) level of sedentary behavior (betaadjusted = - 0.02; 95% CI: - 0.03 to - 0.01; P = 0.006; N = 2769). The results of this brief report do not demonstrate that sedentary behavior, independent of MVPA, is associated with HRQOL. The independent association of MVPA on HRQOL confirms previous work that used self-report measures of MVPA. PMID- 26844173 TI - Menthol cigarette smoking and obesity in young adult daily smokers in Hawaii. AB - This study investigates 1) the relationship between menthol cigarette smoking and obesity and 2) the association of body mass index with the nicotine metabolite ratio among menthol and non-menthol daily smokers aged 18-35 (n = 175). A brief survey on smoking and measures of height and weight, carbon monoxide, and saliva samples were collected from participants from May to December 2013 in Honolulu, Hawaii. Multiple regression was used to estimate differences in body mass index among menthol and non-menthol smokers and the association of menthol smoking with obesity. We calculated the log of the nicotine metabolite ratio to examine differences in the nicotine metabolite ratio among normal, overweight, and obese smokers. Sixty-eight percent of smokers used menthol cigarettes. Results showed that 62% of normal, 54% of overweight, and 91% of obese smokers used menthol cigarettes (p = .000). The mean body mass index was significantly higher among menthol compared with non-menthol smokers (29.4 versus 24.5, p = .000). After controlling for gender, marital status, educational attainment, employment status, and race/ethnicity, menthol smokers were more than 3 times as likely as non-menthol smokers to be obese (p = .04). The nicotine metabolite ratio was significantly lower for overweight menthol smokers compared with non-menthol smokers (.16 versus .26, p = .02) in the unadjusted model, but was not significant after adjusting for the covariates. Consistent with prior studies, our data show that menthol smokers are more likely to be obese compared with non menthol smokers. Future studies are needed to determine how flavored tobacco products influence obesity among smokers. PMID- 26844175 TI - Sodium content of popular commercially processed and restaurant foods in the United States. AB - PURPOSE: The purpose of this study was to provide baseline estimates of sodium levels in 125 popular, sodium-contributing, commercially processed and restaurant foods in the U.S., to assess future changes as manufacturers reformulate foods. METHODS: In 2010-2013, we obtained ~ 5200 sample units from up to 12 locations and analyzed 1654 composites for sodium and related nutrients (potassium, total dietary fiber, total and saturated fat, and total sugar), as part of the U.S. Department of Agriculture-led sodium-monitoring program. We determined sodium content as mg/100 g, mg/serving, and mg/kcal and compared them against U.S. Food and Drug Administration's (FDA) sodium limits for "low" and "healthy" claims and to the optimal sodium level of < 1.1 mg/kcal, extrapolating from the Healthy Eating Index-2010. RESULTS: Results from this study represent the baseline nutrient values to use in assessing future changes as foods are reformulated for sodium reduction. Sodium levels in over half (69 of 125) of the foods, including all main dishes and most Sentinel Foods from fast-food outlets or restaurants (29 of 33 foods), exceeded the FDA sodium limit for using the claim "healthy". Only 13 of 125 foods had sodium values below 1.1 mg/kcal. We observed a wide range of sodium content among similar food types and brands. CONCLUSIONS: Current sodium levels in commercially processed and restaurant foods in the U.S. are high and variable. Targeted benchmarks and increased awareness of high sodium content and variability in foods would support reduction of sodium intakes in the U.S. PMID- 26844176 TI - Role of PCP referral and weight loss in the Hopkins POWER trial. AB - PURPOSE: Primary care providers (PCPs) play an important role in identifying and counseling obese patients to lose weight, but it is unknown whether PCP referral of patients into a weight loss intervention is associated with greater weight loss. The objectives are to determine if PCP referral is associated with greater 1) weight loss, 2) end of study patient-provider relationship quality, and 3) satisfaction and participation rates in the intervention. METHODS: 415 obese patients enrolled in the Hopkins POWER trial from six primary care practices in the Baltimore area. We conducted a secondary analysis of results from the trial using longitudinal mixed-effects model and generalized linear model, adjusting for clinic, sex, age, and race. The primary outcome was absolute weight change from baseline to 24 months. Secondary outcomes were patient-provider relationship quality and satisfaction and participation rates in the intervention. RESULTS: Participants in both PCP and non-PCP referral groups lost a similar amount of weight from baseline to 24 months. PCP referral was not significantly associated with percentage of completed coach contacts, web logins, and satisfaction with trial, but was associated with higher end of study patient-provider relationship quality (p = 0.007). CONCLUSIONS: Our study represents the first of its kind to examine the role of PCP referral of patients into a weight loss trial. While we did not find evidence that PCP referral is associated with increased weight loss, further research is needed to determine how PCPs can use their relationship with patients to promote weight loss and enhance intervention effects. PMID- 26844177 TI - Preliminary efficacy and feasibility of embedding high intensity interval training into the school day: A pilot randomized controlled trial. AB - Current physical activity and fitness levels among adolescents are low, increasing the risk of chronic disease. Although the efficacy of high intensity interval training (HIIT) for improving metabolic health is now well established, it is not known if this type of activity can be effective to improve adolescent health. The primary aim of this study is to assess the effectiveness and feasibility of embedding HIIT into the school day. A 3-arm pilot randomized controlled trial was conducted in one secondary school in Newcastle, Australia. Participants (n = 65; mean age = 15.8(0.6) years) were randomized into one of three conditions: aerobic exercise program (AEP) (n = 21), resistance and aerobic exercise program (RAP) (n = 22) and control (n = 22). The 8-week intervention consisted of three HIIT sessions per week (8-10 min/session), delivered during physical education (PE) lessons or at lunchtime. Assessments were conducted at baseline and post-intervention to detect changes in cardiorespiratory fitness (multi-stage shuttle-run), muscular fitness (push-up, standing long jump tests), body composition (Body Mass Index (BMI), BMI-z scores, waist circumference) and physical activity motivation (questionnaire), by researchers blinded to treatment allocation. Intervention effects for outcomes were examined using linear mixed models, and Cohen's d effect sizes were reported. Participants in the AEP and RAP groups had moderate intervention effects for waist circumference (p = 0.024), BMI z (p = 0.037) and BMI (not significant) in comparison to the control group. A small intervention effect was also evident for cardiorespiratory fitness in the RAP group. PMID- 26844178 TI - Correlates of longitudinal changes in the waist-to-height ratio of primary school children: Implications for prevention. AB - OBJECTIVE: To investigate correlates of changes in waist-to-height ratio (WHtR) in primary school children in order to identify modifiable factors usable for prevention. METHODS: Outcome evaluation of a statewide health promotion program in Baden-Wurttemberg, Germany. Baseline (2010) and follow-up (2011) measurements provided data for the calculation of changes in WHtR. Further information on the health and living conditions of the children were assessed in parental questionnaires. Anthropometric measures were taken in 1733 (50.8% male) first and second grade children (age at baseline 7.1 +/- 0.6 years) by staff trained according to ISAK-standards. Stepwise linear regression analysis was applied to identify variables with influence on changes in WHtR. RESULTS: According to the resulting regression model, changes in WHtR towards an increase were influenced by at least one parent being overweight/obese, at least one parent who smoked, low household income, higher age of the child and the skipping of breakfast. There was no clustering effect in schools observed. CONCLUSION: A promising target for prevention of gain in WHtR in primary school children is to ensure the regularity of breakfast. Smoking cessation as well as dietary improvements would not only help children's health but also the health of their parents. The socioeconomic influence on the development of an unhealthy weight status has already been acknowledged and should be extensively targeted by all of society and policy makers. PMID- 26844179 TI - Increasing physical activity levels in primary school physical education: The SHARP Principles Model. AB - OBJECTIVES: To evaluate the effectiveness of a one-year teaching intervention to increase moderate to vigorous physical activity (MVPA) during primary school physical education (PE). METHODS: A quasi-experimental, non-equivalent group design involving four classes from two primary schools in the West Midlands, UK. In March 2014 schools were selected through purposive sampling to match schools in terms of size and demographics (baseline, n = 111: post-intervention, n = 95); data were collected from children in school years 3 and 4 (aged 7 to 9 years). The intervention involved developing teacher effectiveness through the SHARP Principles Model which was grounded in the Self Determination Theory (SDT), the Social Ecological Model (SEM) and three key ingredients from the Behaviour Change Taxonomy (BCT). MVPA was assessed at baseline and four weeks post-intervention using the System for Observing Fitness and Instruction Time (SOFIT). Four individual teacher interviews were conducted with the intervention school, to explore teachers' perceptions of the intervention. RESULTS: A two-way ANOVA (Analysis of Variance) indicated large interaction effect sizes for time spent in MVPA (F(1, 27) = 11.07, p = 0.003, etap (2) = .316) and vigorous activity (VPA) (F = (1,27) = 8.557, p = .007, etap (2) = .263). PA in the intervention school increased significantly whereas in the control school MVPA remained relatively constant and VPA decreased. The qualitative findings revealed two main emergent themes: a paradigm shift and teacher's developing pedagogy. CONCLUSIONS: The intervention was effective in increasing MVPA in PE. Recommendations based on this evaluation would be for the SHARP Principles Model to be replicated and evaluated on a wider scale across a variety of contexts. PMID- 26844180 TI - Adherence to Canadian physical activity and sedentary behaviour guidelines among children 2 to 13 years of age. AB - Active living is relevant for healthy child development and disease prevention. In 2011-2012 new Canadian Physical Activity and Sedentary Behaviour Guidelines were developed for children under four and 5-17 years of age. This cross sectional study assessed children's adherence to the national guidelines, using a large sample of Alberta children ages 2-4 and 5-13 years in 2013. The proportions of children achieving the average daily duration of physical activity and screen time recommended were determined, and child and parental predictors of non achievement were identified. Participants were 631 parent and child dyads. Data were collected by parental reports of physical activity and screen time during weekdays, and analysed using univariate and multivariate techniques (p < 0.05). Logistic regression models were used to examine factors associated with children's non-achievement of physical activity and screen time recommendations while adjusting for covariates. Sixty-two percent of children aged 2-4 and 26% of children aged 5-13 did not meet physical activity time recommendations, and 64% of children aged 2-4 and 23% of children aged 5-13 exceeded the maximum screen time recommendation. Several associations between parental age and education with non-achievement were observed but associations were not consistent across age groups or behaviours. Among preschoolers, those with middle-age parents were more likely to not achieve physical activity recommendations. Evidence of high non achievement of the recommendations among children 2-4 years highlights the need for increased programming targeting preschool children. Further research is required to identify modifiable risk factors that may inform future health promotion efforts. PMID- 26844181 TI - Cost of accidental carbon monoxide poisoning: A preventable expense. AB - Carbon monoxide (CO) poisoning is common in the United States, accounting for hundreds of deaths and thousands of emergency department visits annually. It is believed that most accidental CO poisoning is preventable through public education, warning labels on consumer products, and uniform use of residential CO alarms. However, cost effectiveness of these prevention strategies has not been demonstrated in the United States to date. It was the objective of this study to estimate societal cost of accidental CO poisoning and evaluate the cost effectiveness of universal installation of residential CO alarms. Published studies and data from the English language literature were used in to estimate direct hospital costs and lost earnings resulting from accidental CO poisoning. The study was performed in the US in 2015. Approximately 6600 individuals are estimated to sustain long-term cognitive sequela annually, with total loss in earnings of approximately $925 million, 334 individuals die from accidental, non fire related CO poisoning with an average loss of 26 years of productivity accounting for $355 million, and 2800 are hospitalized with acute medical care costs of $33 million. Available data indicate that accidental CO poisoning in the US conservatively costs society over $1.3 billion, resulting from direct hospital costs and lost earnings. Further, it demonstrates a positive cost-benefit ratio for the uniform use of residential CO alarms. PMID- 26844182 TI - Generation status as a determinant of influenza vaccination among Mexican identified adults in California, 2011-12. AB - First generation Latinos often have better health behaviors and outcomes than second and third generation Latinos. This study examined the correlates of seasonal influenza vaccinations among Mexican-identified (Mexican) adults, who make up the largest Latino subgroup in California. A sample of Mexican adults (N = 7493) from the 2011-12 California Interview Health Survey was used to compare the odds of first, second, and third generation Mexicans receiving influenza vaccinations in the past year. We performed a logistic regression taking into account socio-demographic characteristics, health status, and access to care. We repeated the analysis after stratifying for nativity, and then age. Being a second (odds ratio (OR) = 0.74, confidence interval (CI): 0.59, 0.92) and third generation or higher (OR = 0.66, CI: 0.51, 0.86) Mexican was associated with lower odds of getting an influenza vaccination compared to first generation Mexicans. Having a chronic disease, and access to care was associated with higher odds of vaccination, while lower age was associated with lower odds of vaccination among both US-, and foreign-born Mexicans. Given that the majority of Mexicans in California are US-born, the fact that being second- and third generation Mexicans was associated with lower influenza vaccination rates is of significant concern. PMID- 26844183 TI - Physical activity of workers with and without chronic diseases. AB - OBJECTIVE: To contribute to the development of measures that increase physical activity (PA) levels in workers with and without chronic diseases, insight into workers' PA level is needed. Therefore, this study examined the association between the number of chronic diseases and PA in a Dutch working population. METHODS: Data of 131,032 workers from the Dutch Public Health Monitor 2012 were used in this cross-sectional study conducted in 2015 in the Netherlands. PA was operationalized as adherence (yes/no) to three PA guidelines. One of these was the American College of Sports Medicine (ACSM) guideline (>= 3 days/week, >= 20 min/day of vigorous-intensity activities). Also, the amount of moderate- and vigorous-intensity PA in min/week for those who were physically active for > 0 min/week was calculated. Associations between chronic diseases (0, 1, >= 2 chronic diseases) and PA were examined using logistic regression and Generalized Estimating Equations stratified for age (19-54 years/55-64 years). RESULTS: Workers aged 19-54 years with one (OR = 0.90 (99% CI = 0.84-0.95)) and multiple chronic diseases (OR = 0.76 (99% CI = 0.69-0.83)) had lower odds of adhering to the ACSM-guideline than workers without chronic diseases. Similar patterns were found for older workers. Younger workers with one (B = 24.44 (99% CI = 8.59 40.30)) and multiple chronic diseases (B = 49.11 (99% CI = 26.61-71.61)) had a higher amount of moderate PA than workers without chronic diseases. CONCLUSION: Workers with chronic diseases adhered less often to the ACSM-guideline, but among workers aged 19-54 years who were physically active for > 0 min/week, those with chronic diseases spent more time in moderate-intensity PA than those without chronic diseases. PMID- 26844184 TI - Time spent sitting during and outside working hours in bus drivers: A pilot study. AB - This cross-sectional pilot study objectively measured sedentary and non-sedentary time in a sample of bus drivers from the East Midlands, United Kingdom. Participants wore an activPAL3 inclinometer for 7 days and completed a daily diary. Driver's blood pressure, heart rate, waist circumference and body composition were measured objectively at the outset. The proportions of time spent sedentary and non-sedentary were calculated during waking hours on workdays and non-workdays and during working-hours and non-working-hours on workdays. 28 (85% of those enrolled into the study) provided valid objective monitoring data (89.3% male, [median +/- IQR] age: 45.2 +/- 12.8 years, BMI 28.1 +/- 5.8 kg/m(2)). A greater proportion of time was spent sitting on workdays than non workdays (75% [724 +/- 112 min/day] vs. 62% [528 +/- 151 min/day]; p < 0.001), and during working-hours than non-working-hours (83% [417 +/- 88 min/day] vs. 68% [307 +/- 64 min/day]; p < 0.001) on workdays. Drivers spent less than 3% of their overall time stepping. Bus drivers accumulate high levels of sitting time during working-hours and outside working-hours. Interventions are urgently needed in this at-risk group, which should focus on reducing sitting and increasing movement during breaks and increasing physical activity during leisure time to improve cardiovascular health. PMID- 26844185 TI - Human development, occupational structure and physical inactivity among 47 low and middle income countries. AB - This study aimed to (a) assess the relationship between a person's occupational category and their physical inactivity, and (b) analyze the association among country-level variables and physical inactivity. The World Health Survey (WHS) was administered in 2002-2003 among 47 low- and middle-income countries (n = 196,742). The International Physical Activity Questionnaire (IPAQ) was used to collect verbal reports of physical activity and convert responses into measures of physical inactivity. Economic development (GDP/c), degree of urbanization, and the Human Development Index (HDI) were used to measure country-level variables and physical inactivity. Multilevel logistic regression analysis was used to examine the association among country-level factors, individual occupational status, and physical inactivity. Overall, the worldwide prevalence of physical inactivity in 2002-2003 was 23.7%. Individuals working in the white-collar industry compared to agriculture were 84% more likely to be physically inactive (OR: 1.84, CI: 1.73-1.95). Among low- and middle-income countries increased HDI values were associated with decreased levels of physical inactivity (OR: 0.98, CI: 0.97-0.99). This study is one of the first to adjust for within-country differences, specifically occupation while analyzing physical inactivity. As countries experience economic development, changes are also seen in their occupational structure, which result in increased countrywide physical inactivity levels. PMID- 26844186 TI - Bouted and non-bouted moderate-to-vigorous physical activity with health-related quality of life. AB - Examine the association between bouted (10 + minutes in duration) and non-bouted (< 10 minutes in duration) moderate-to-vigorous physical activity (MVPA) with health-related quality of life (HRQOL). Data from the 2003-2006 NHANES were used (20 + years; N = 5530). Participants wore an ActiGraph 7164 accelerometer over a period of up to 7 days to assess accumulation in bouted and non-bouted MVPA. From 4 self-reported items, HRQOL was assessed using the CDC HRQOL-4 questionnaire, with a higher HRQOL-4 score indicating worse HRQOL. In a single multivariable ordinal regression analysis, both non-bout (betaadjusted = - 0.01; 95% CI: - 0.01 to - 0.003; P = 0.006) and bouted (betaadjusted = - 0.08; 95% CI: - 0.15 to - 0.01; P = 0.01) MVPA were associated with HRQOL. Greater accumulation in both bouted and non-bouted MVPA was associated with better perceived HRQOL. PMID- 26844187 TI - Breakfast and fast food consumption are associated with selected biomarkers in adolescents. AB - OBJECTIVE: Skipping breakfast and consuming fast food are related to the risk of obesity and are common adolescent behaviors. The relationship between these behaviors and biomarkers related to diabetes and CVD is understudied in this population. METHODS: Data are from a study of the etiologic factors related to obesity risk in adolescents. Breakfast and fast food consumption were assessed using a self-report survey. Anthropometrics, fasting lipids, glucose, insulin, and homeostatic model assessment for insulin resistance (HOMA-IR) were assessed. Multivariate analyses were used to examine the relationship between dietary behaviors and selected biomarkers, controlling for calories consumed, body mass index (BMI), and demographic covariates. RESULTS: 367 adolescents (11 to 18 years; mean 14.7 +/- 1.8 years) were assessed at the University of Minnesota-Twin Cities from 2006-2008. Breakfast consumption was significantly associated with lower BMI, body fat, insulin, HOMA-IR, and metabolic syndrome (MetS) cluster score, while fast food consumption was associated with higher BMI, body fat, low density lipoprotein cholesterol, triglycerides, glucose, insulin, HOMA-IR, and MetS cluster score. Some gender differences were observed. CONCLUSION: Breakfast and fast food consumption appear to be related to important metabolic syndrome biomarkers for chronic disease in a sample of healthy adolescents. The importance of this finding needs to be validated by examining the stability of this pattern over time and to assess the pattern in other populations. PMID- 26844188 TI - Features of the UK childcare environment and associations with preschooler's in care physical activity. AB - OBJECTIVE: Features of the childcare environment may influence children's in-care physical activity (PA). We assessed the association between UK preschool care provider, environmental and policy factors and 3-4-year-olds' average daily in care sedentary behaviour (SED) and PA. METHODS: In 2013, we used accelerometers to measure the in-care SED/ PA of 201 3-4-year-old children (51% female) in 30 preschools in Cambridgeshire, UK, (average wear time: (mean +/- SD) 4.2 +/- 1.3 week-days). We assessed the childcare environment using the Environment and Policy Assessment and Observation tool; demographic and carer information was taken from questionnaires. We used three-level mixed-effects regression analyses (adjusted for sex, in-care time and travel mode to care) to determine the association between childcare factors and children's in-care average daily minutes/hour spent SED, in light PA (LPA) and in moderate-to-vigorous PA (MVPA). RESULTS: Children spent 5.6 +/- 2.5 h in care per day on average; clustering of PA within preschools was limited (ICCs: 0.003-0.05). Fully adjusted models showed that active opportunities were positively associated with children's in-care SED. No associations with in-care LPA and MVPA were observed. CONCLUSION: Few care provider, environmental and policy factors were associated with children's in care activity. UK childcare policies advocating child-driven play, moving freely indoors and outdoors, may be more conducive to individual children's PA. PMID- 26844189 TI - Association between accelerometer-determined physical activity and flavonoid-rich fruit and vegetable consumption among a national sample of U.S. adults. AB - Few population studies have examined the association between accelerometer assessed physical activity and dietary behavior. Further, no studies have systematically examined the association between accelerometer-assessed physical activity and flavonoid rich fruits and vegetables in a national sample. As a result, the purpose of this study was to examine the association between objectively measured physical activity and consumption of flavonoid rich fruits and vegetables among a national sample of U.S. adults. Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used (N = 2949). Physical activity was measured via accelerometry and fruit and vegetable consumption was measured from the NHANES Food Frequency Questionnaire. After adjustments, moderate-to-vigorous physical activity was positively associated (p < 0.05) with apples (beta = 0.30), grapes (beta = 0.27), strawberries (beta = 0.32), oranges (beta = 0.35), raw greens (beta = 0.19), carrots (beta = 0.23), peppers (beta = 0.29) and an overall flavonoid index variable (beta = 2.34). Future studies employing a longitudinal design are needed to better understand the direction of the observed associations. If future studies do indeed support the possibility that physical activity may help to foster changes in dietary behavior, then this will have strong implications for health behavior interventions, particularly among individuals finding it difficult to change multiple health behaviors concurrently. PMID- 26844190 TI - Unmet needs for dental care in children with special health care needs. AB - OBJECTIVE: The unmet need for dental care is one of the greatest public health problems facing U.S. children. This issue is particularly concerning for children with special health care needs (CSHCN), who experience higher prevalence of unmet dental care needs. The primary purpose of this study was to investigate regional differences in unmet dental care needs for CSHCN. Using the Social Ecological Model as a framework, additional variables were analyzed for regional differences. It was hypothesized that (H1) unmet dental care needs would be high in the CSHCN population, (H2) there would be regional differences in unmet dental care needs in CSHCN, and (H3) there would be differences in specific individual, interpersonal (family), community (state), and policy level factors by region. METHODS: Data were obtained from the 2009-2010 National Survey of CSHCN. SPSS was used for data management and analysis. RESULTS: Each of the study hypotheses was supported for the sample of 40,242 CSHCN. The West region was more likely to have more unmet needs for preventive and specialized dental care in CSHCN than the reference region (Northeast). The South region followed the West region in unmet dental care needs. Statistically significant differences in individual, interpersonal (family), community (state) and policy factors were found by region. CONCLUSION: Further research is recommended. Effective strategies that include policy to address unmet dental care needs at multiple levels of intervention are suggested. PMID- 26844191 TI - More standing and just as productive: Effects of a sit-stand desk intervention on call center workers' sitting, standing, and productivity at work in the Opt to Stand pilot study. AB - This study evaluated the effects of sit-stand desks on workers' objectively and subjectively assessed sitting, physical activity, and productivity. This quasi experimental study involved one intervention group (n = 16) and one comparison group (n = 15). Participants were call center employees from two job-matched teams at a large telecommunications company in Sydney, Australia (45% female, 33 +/- 11 years old). Intervention participants received a sit-stand desk, brief training, and daily e-mail reminders to stand up more frequently for the first 2 weeks post-installation. Control participants carried out their usual work duties at seated desks. Primary outcomes were workday sitting and physical activity assessed using ActivPAL or ActiGraph devices and self-report questionnaires. Productivity outcomes were company-specific objective metrics (e.g., hold time, talking time, absenteeism) and subjective measures. Measurements were taken at baseline, 1, 4, and 19 weeks post-installation. Intervention participants increased standing time after 1 week (+ 73 min/workday (95% CI: 22, 123)) and 4 weeks (+ 96 min/workday (95% CI: 41, 150)) post-intervention, while control group showed no changes. Between-group differences in standing time at one and 4 weeks were + 78 (95% CI: 9, 147) and + 95 min/workday (95% CI: 15, 174), respectively. Sitting time in the intervention group changed by - 64 (95% CI: - 125, - 2), - 76 (95% CI: - 142, - 11), and - 100 min/workday (95% CI: - 172, - 29) at 1, 4, and 19 weeks post-installation, respectively, while the control group showed no changes. No changes were observed in productivity outcomes from baseline to follow-up in either group. Sit-stand desks can increase standing time at work in call center workers without reducing productivity. PMID- 26844192 TI - The impact of body mass index on the associations of lipids with the risk of coronary heart disease in the Asia Pacific region. AB - OBJECTIVE: To assess whether body mass index (BMI) modifies the associations of lipids with coronary heart disease (CHD). METHODS: In the Asia Pacific Cohort Studies Collaboration, total cholesterol (TC), high density lipoprotein cholesterol (HDLC) and triglycerides (TG) were measured for 333,297, 71,777 and 84,015 participants, respectively. All participants had measured BMI, categorized into underweight, normal, high-normal, overweight and obese, using standard definitions. For each BMI subgroup the effects of lipids on CHD were estimated per 1 standard deviation (SD) increase using Cox proportional hazard models, stratified by study and sex, adjusted for age and smoking. They were compared across the BMI groups, testing for interactions. RESULTS: In the analyses for TC, HDLC and TG, there were 3121, 714 and 808 CHD events during a mean follow-up of 6.7 years. The risk of CHD increased monotonically with increasing TC and decreasing HDLC in all BMI subgroups without evidence of heterogeneity (p for interaction > 0.4). In contrast, the hazard ratio for CHD for a one SD increase in log-transformed TG increased from 1.07 (95%CI 0.72-1.59) in underweight, 1.26 (1.10-1.44) in normal weight, 1.27 (1.08-1.49) in high-normal weight, 1.37 (1.22 1.55) in overweight, to 1.61(1.30-1.99) in obesity (p = 0.01 for interaction trend). These associations were attenuated (p = 0.07 for interaction) but remained significant in the overweight and obese after further adjustment for TC and HDLC. CONCLUSIONS: Greater excess body weight exacerbated the effects of TG, but not TC or HDLC, on CHD, suggesting that additional effort is required to reduce TG in the overweight and obese. PMID- 26844193 TI - Effectiveness of a drinking-motive-tailored emergency-room intervention among adolescents admitted to hospital due to acute alcohol intoxication - A randomized controlled trial. AB - The aim of this study is to develop and test the effectiveness of a drinking motive-tailored intervention for adolescents hospitalized due to alcohol intoxication in eight cities in Germany between December 2011 and May 2012 against a similar, non-motive-tailored intervention. In a randomized controlled trial, 254 adolescents received a psychosocial intervention plus motive-tailored (intervention group; IG) or general exercises (control group; CG). Adolescents in the IG received exercises in accordance with their drinking motives as indicated at baseline (e.g. alternative ways of spending leisure time or dealing with stress). Exercises for the CG contained alcohol-related information in general (e.g. legal issues). The data of 81 adolescents (age: M = 15.6, SD = 1.0; 42.0% female) who participated in both the baseline and the follow-up were compared using ANOVA with repeated measurements and effect sizes (available case analyses). Adolescents reported lower alcohol use at the four-week follow-up independently of the kind of intervention. Significant interaction effects between time and IG were found for girls in terms of drinking frequency (F = 7.770, p < 0.01) and binge drinking (F = 7.0005, p < 0.05) but not for boys. For the former, the proportional reductions and corresponding effect sizes of drinking frequency (d = - 1.18), binge drinking (d = - 1.61) and drunkenness (d = - 2.87) were much higher than the .8 threshold for large effects. Conducting psychosocial interventions in a motive-tailored way appears more effective for girls admitted to hospital due to alcohol intoxication than without motive tailoring. Further research is required to address the specific needs of boys in such interventions. (German Clinical Trials Register, DRKS ID: DRKS00005588). PMID- 26844194 TI - Age-related comparisons by sex in the domains of aerobic physical activity for adults in Scotland. AB - OBJECTIVE: To investigate the age-related differences in the contributions of the domains of physical activity (PA) for men and women in Scotland who met the current PA guidelines or who were insufficiently active. METHODS: We analysed data from the 2013 Scottish Health Survey (4885 adults (>= 16 years)). Average weekly minutes of moderate or vigorous PA (MVPA) and the relative contributions to total MVPA were calculated for the domains of: walking, cycling, domestic, leisure, occupational, outdoor, non-team sport, team sport, and exercise & fitness. We performed linear regression analyses to assess differences by 10-year age group, stratified by sex and activity status (1-149 or >= 150 min of MVPA per week). These were repeated excluding occupational activity due to concerns with its measurement. RESULTS: For the 64.3% of the sample that met the guidelines, occupational activity was the most prevalent domain accounting for 18-26% of all MVPA for those under 65 years. When excluded, there was no age-related decline in total MVPA (p > 0.05). For the 18.6% of the sample that reported 1-149 min of MVPA per week, domestic activity was the most prevalent domain. Across both sexes and activity statuses, exercise & fitness declined with age and walking was most prevalent in the oldest age group. CONCLUSION: The domains in which adults in Scotland undertake MVPA vary by age group. Policies designed to increase PA should take this into account. Our findings challenge current thinking on age related changes in activity, with the exclusion of occupational activity mitigating any age-related decline in MVPA. PMID- 26844195 TI - Individual, family, and neighborhood correlates of independent mobility among 7 to 11-year-olds. AB - Objective. Independent mobility refers to the freedom that children have to move around their neighborhood without adult supervision. It is related to their physical activity and health. We examined the intrapersonal, family, and neighborhood correlates of independent mobility within children. Methods. 497 American parents of 6.9-11.9 year olds completed a survey (November, 2014) that assessed their child's independent mobility range, several intrapersonal characteristics of their child (gender, age, race, etc.), several characteristics of their family (family structure, socioeconomic status, parental physical activity, etc.), and their perceptions of the safety of their neighborhood (18 questions reduced to 4 components). Associations were determined using ordinal logistic regression. Results. Children's age, parent's perception that their neighborhood is safe for children, and parent's fear of neighborhood crime were the independent correlates of independent mobility. Compared to 6.9-7.9 year olds, the odds ratio (95% CI) for increasing independent mobility were 2.31 (1.47 3.64) in 8.0-9.9 year olds and 3.38 (2.13-5.36) in 10.0-11.9 year olds. Compared to children whose parents who did not perceive that their neighborhood was safe for children, the odds ratio for increasing independent mobility was 4.24 (2.68 6.70) for children whose parents perceived their neighborhood was safe for children. Compared to children whose parents had the lowest fear of neighborhood crime, the odds ratio for increasing independent mobility was 0.41 (0.27-0.62) for children whose parents had the highest fear of crime. Conclusions. Children's independent mobility was associated with their age, their parent's perception that their neighborhood was safe for children, and their parent's fear of crime. PMID- 26844196 TI - A systematic review of the health benefits of Tai Chi for students in higher education. AB - BACKGROUND: The poor health consequences of stress are well recognized, and students in higher education may be at particular risk. Tai Chi integrates physical exercise with mindfulness techniques and seems well suited to relieve stress and related conditions. METHODS: We conducted a systematic review of the health benefits of Tai Chi for students in higher education reported in the English and Chinese literature, using an evidence hierarchy approach, allowing the inclusion of studies additional to randomized controlled trials. RESULTS: Sixty eight reports in Chinese and 8 in English were included - a combined study sample of 9263 participants. Eighty one health outcomes were extracted from reports, and assigned evidence scores according to the evidence hierarchy. Four primary and eight secondary outcomes were found. Tai Chi is likely to benefit participants by increasing flexibility, reducing symptoms of depression, decreasing anxiety, and improving interpersonal sensitivity (primary outcomes). Secondary outcomes include improved lung capacity, balance, 800/1000m run time, quality of sleep, symptoms of compulsion, somatization and phobia, and decreased hostility. CONCLUSIONS: Our results show Tai Chi yields psychological and physical benefits, and should be considered by higher education institutions as a possible means to promote the physical and psychological well-being of their students. PMID- 26844197 TI - Physical activity counseling in overweight and obese primary care patients: Outcomes of the VA-STRIDE randomized controlled trial. AB - The purpose of this 2-arm randomized clinical trial was to evaluate the effectiveness of a 12-month, expert system-based, print-delivered physical activity intervention in a primary care Veteran population in Pittsburgh, Pennsylvania. Participants were not excluded for many health conditions that typically are exclusionary criteria in physical activity trials. The primary outcome measures were physical activity reported using the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire and an accelerometer based activity assessment at baseline, 6, and 12 months. Of the 232 Veterans enrolled in the study, 208 (89.7%) were retained at the 6-month follow-up and 203 (87.5%) were retained at 12 months. Compared to the attention control, intervention participants had significantly increased odds of meeting the U.S. recommended guideline of >= 150 min/week of at least moderate-intensity physical activity at 12 months for the modified CHAMPS (odds ratio [OR] = 2.86; 95% CI: 1.03-7.96; p = 0.04) but not at 6 months (OR = 1.54; 95% CI: 0.56-4.23; p = 0.40). Based on accelerometer data, intervention participants had significantly increased odds of meeting >= 150 min/week of moderate-equivalent physical activity at 6 months (OR = 6.26; 95% CI: 1.26-31.22; p = 0.03) and borderline significantly increased odds at 12 months (OR = 4.73; 95% CI: 0.98-22.76; p = 0.053). An expert system physical activity counseling intervention can increase or sustain the proportion of Veterans in primary care meeting current recommendations for moderate-intensity physical activity. Trial Registration Clinical trials.gov identifier: NCT00731094 URL: http://www.clinicaltrials.gov/ct2/show/NCT00731094. PMID- 26844198 TI - Combined effects of maternal age and parity on successful initiation of exclusive breastfeeding. AB - Maternal age at first childbirth has increased in most developed countries in the past 20 years. The purpose of this study is to investigate effects of maternal age at delivery and parity on successful initiation of exclusive breastfeeding (EBF). This retrospective study investigated 1193 singleton dyads with vaginal delivered at 37-42 gestational weeks during January and December in 2011 at one large "Baby-Friendly" certified hospital in Japan. A multivariate logistic regression model was used to evaluate individual and combined effects of maternal age and parity on successful initiation of EBF after adjusted for pre-pregnancy body mass index, gestational weight gain, pregnancy complications, mothers' underlying illness, smoking and alcohol drinking habits, gestational week at delivery, child's sex and nurturing support from grandparents. Success rates of EBF at one month after child delivery was 69.4% in primiparous aged >= 35 (group A: n = 284), 73.5% in multiparous aged >= 35 (group B: n = 268), 74.3% in primiparous aged < 35 (group C: n = 432), and 82.3% in multiparous aged < 35 (group D: n = 209). Older maternal age and primiparous became independently associated with EBF initiation. The combined effect for successful initiation of EBF was the lowest in group A referent to group D both at discharge and at one month (odds ratio (OR) 5.9, 95% confidence interval (CI): 3.0-11.9, and OR 2.2, 95% CI: 1.4-3.4, respectively). Primiparous mothers in late child-bearing aged 35 years or older are at the greatest risk of EBF initiation. PMID- 26844199 TI - Survival effects of physical activity on mortality among persons with liver disease. AB - Physical activity is protective of premature mortality and those with liver disease are at an increased risk of early mortality. It is thus plausible to suggest that physical activity may have survival benefits among those with liver disease, but this has yet to be investigated. In a national sample, we examine the prospective association of objectively-measured physical activity on all cause mortality among those with liver disease. Data from the 2003-2006 National Health and Nutrition Examination Survey (with follow-up through 2011) were evaluated (analyzed in 2015). Physical activity was assessed via accelerometry over 7 days. Liver disease was assessed via self-report of physician diagnosis. Covariates included age, gender, race-ethnicity, serum cotinine, income-to poverty ratio, C-reactive protein, cholesterol medication use, blood pressure medication use, alcohol behavior, self-reported liver disease status, serum alanine aminotransferase (ALT), serum gamma-glutamyltransferase (GGT) and comorbid illness. The sample included 162 adults who self-reported a physician diagnosis of liver disease. The unweighted median follow-up period was 80.0 months (IQR = 68-91; SD = 18.0). In the sample, 12,815 person-months occurred with a mortality incidence rate of 1.09 deaths per 1000 person-months. After adjustments, for every 10 min/day increase in moderate-to-vigorous physical activity (MVPA), participants had an 89% reduced risk of all-cause mortality (HRadjusted = 0.11; 95% CI: 0.02-0.47; P = 0.004). There was no evidence of moderation by alcohol behavior, ALT, GGT or Hepatitis C virus status. These findings demonstrate that modest increases in MVPA may have survival benefits among those with a self-reported liver condition. PMID- 26844200 TI - Validation of self-rated overall diet quality by Healthy Eating Index-2010 score among New York City adults, 2013. AB - OBJECTIVE: Chronic conditions such as cardiovascular disease and cancer can result from a number of diet-related environmental and behavioral factors. Screening for poor diet is helpful in developing interventions to prevent chronic disease, but measuring dietary behavior can be costly and time-consuming. The purpose of this study was to test the ability of a self-rated, single-item measure for evaluating diet quality among individuals and populations. METHODS: A 24-h dietary recall and single-item self-rated diet quality measure were collected for 485 adults. From dietary recalls, Healthy Eating Index-2010 (HEI) scores were computed and compared with self-rated diet quality. Data were collected in 2013 among adult (18 years and older) New York City residents. RESULTS: The study sample was 57% female, 47% white, 56% college educated, and 45% in the highest income tertile. The mean HEI score was 56.5 out of a possible 100. Women averaged higher HEI scores compared to men (58.1 vs 54.3, p = .01). There was a modest yet significant correlation between HEI scores and self-rated diet quality (rho = 0.29, p < .01). Overall, mean HEI score increased as self rated diet quality improved (from 48.2 for "poor" to 63.0 for "excellent"). CONCLUSIONS: The single-item measure of self-rated diet quality may provide a simple method of identifying those with the worst diet quality. Further investigation of this measure's validity is needed with alternative measures of dietary intake and with health outcomes. PMID- 26844201 TI - Hunger: The carrot and the stick. PMID- 26844202 TI - Chewing the fat for better insulin secretion. PMID- 26844204 TI - Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis. AB - BACKGROUND: Stress-associated conditions such as psychoemotional reactivity and depression have been paradoxically linked to either weight gain or weight loss. This bi-directional effect of stress is not understood at the functional level. Here we tested the hypothesis that pre-stress level of adaptive thermogenesis and brown adipose tissue (BAT) functions explain the vulnerability or resilience to stress-induced obesity. METHODS: We used wt and triple beta1,beta2,beta3 Adrenergic Receptors knockout (beta-less) mice exposed to a model of chronic subordination stress (CSS) at either room temperature (22 degrees C) or murine thermoneutrality (30 degrees C). A combined behavioral, physiological, molecular, and immunohistochemical analysis was conducted to determine stress induced modulation of energy balance and BAT structure and function. Immortalized brown adipocytes were used for in vitro assays. RESULTS: Departing from our initial observation that betaARs are dispensable for cold-induced BAT browning, we demonstrated that under physiological conditions promoting low adaptive thermogenesis and BAT activity (e.g. thermoneutrality or genetic deletion of the betaARs), exposure to CSS acted as a stimulus for BAT activation and thermogenesis, resulting in resistance to diet-induced obesity despite the presence of hyperphagia. Conversely, in wt mice acclimatized to room temperature, and therefore characterized by sustained BAT function, exposure to CSS increased vulnerability to obesity. Exposure to CSS enhanced the sympathetic innervation of BAT in wt acclimatized to thermoneutrality and in beta-less mice. Despite increased sympathetic innervation suggesting adrenergic-mediated browning, norepinephrine did not promote browning in betaARs knockout brown adipocytes, which led us to identify an alternative sympathetic/brown adipocytes purinergic pathway in the BAT. This pathway is downregulated under conditions of low adaptive thermogenesis requirements, is induced by stress, and elicits activation of UCP1 in wt and beta-less brown adipocytes. Importantly, this purinergic pathway is conserved in human BAT. CONCLUSION: Our findings demonstrate that thermogenesis and BAT function are determinant of the resilience or vulnerability to stress-induced obesity. Our data support a model in which adrenergic and purinergic pathways exert complementary/synergistic functions in BAT, thus suggesting an alternative to betaARs agonists for the activation of human BAT. PMID- 26844203 TI - Adipose tissue glycogen accumulation is associated with obesity-linked inflammation in humans. AB - OBJECTIVE: Glycogen metabolism has emerged as a mediator in the control of energy homeostasis and studies in murine models reveal that adipose tissue might contain glycogen stores. Here we investigated the physio(patho)logical role of glycogen in human adipose tissue in the context of obesity and insulin resistance. METHODS: We studied glucose metabolic flux of hypoxic human adipoctyes by nuclear magnetic resonance and mass spectrometry-based metabolic approaches. Glycogen synthesis and glycogen content in response to hypoxia was analyzed in human adipocytes and macrophages. To explore the metabolic effects of enforced glycogen deposition in adipocytes and macrophages, we overexpressed PTG, the only glycogen associated regulatory subunit (PP1-GTS) reported in murine adipocytes. Adipose tissue gene expression analysis was performed on wild type and homozygous PTG KO male mice. Finally, glycogen metabolism gene expression and glycogen accumulation was analyzed in adipose tissue, mature adipocytes and resident macrophages from lean and obese subjects with different degrees of insulin resistance in 2 independent cohorts. RESULTS: We show that hypoxia modulates glucose metabolic flux in human adipocytes and macrophages and promotes glycogenesis. Enforced glycogen deposition by overexpression of PTG re-orients adipocyte secretion to a pro-inflammatory response linked to insulin resistance and monocyte/lymphocyte migration. Furthermore, glycogen accumulation is associated with inhibition of mTORC1 signaling and increased basal autophagy flux, correlating with greater leptin release in glycogen-loaded adipocytes. PTG-KO mice have reduced expression of key inflammatory genes in adipose tissue and PTG overexpression in M0 macrophages induces a pro-inflammatory and glycolytic M1 phenotype. Increased glycogen synthase expression correlates with glycogen deposition in subcutaneous adipose tissue of obese patients. Glycogen content in subcutaneous mature adipocytes is associated with BMI and leptin expression. CONCLUSION: Our data establish glycogen mishandling in adipose tissue as a potential key feature of inflammatory-related metabolic stress in human obesity. PMID- 26844205 TI - Skeletal muscle salt inducible kinase 1 promotes insulin resistance in obesity. AB - OBJECTIVE: Insulin resistance causes type 2 diabetes mellitus and hyperglycemia due to excessive hepatic glucose production and inadequate peripheral glucose uptake. Our objectives were to test the hypothesis that the proposed CREB/CRTC2 inhibitor salt inducible kinase 1 (SIK1) contributes to whole body glucose homeostasis in vivo by regulating hepatic transcription of gluconeogenic genes and also to identify novel SIK1 actions on glucose metabolism. METHODS: We created conditional (floxed) SIK1-knockout mice and studied glucose metabolism in animals with global, liver, adipose or skeletal muscle Sik1 deletion. We examined cAMP-dependent regulation of SIK1 and the consequences of SIK1 depletion on primary mouse hepatocytes. We probed metabolic phenotypes in tissue-specific SIK1 knockout mice fed high fat diet through hyperinsulinemic-euglycemic clamps and biochemical analysis of insulin signaling. RESULTS: SIK1 knockout mice are viable and largely normoglycemic on chow diet. On high fat diet, global SIK1 knockout animals are strikingly protected from glucose intolerance, with both increased plasma insulin and enhanced peripheral insulin sensitivity. Surprisingly, liver SIK1 is not required for regulation of CRTC2 and gluconeogenesis, despite contributions of SIK1 to hepatocyte CRTC2 and gluconeogenesis regulation ex vivo. Sik1 mRNA accumulates in skeletal muscle of obese high fat diet-fed mice, and knockout of SIK1 in skeletal muscle, but not liver or adipose tissue, improves insulin sensitivity and muscle glucose uptake on high fat diet. CONCLUSIONS: SIK1 is dispensable for glycemic control on chow diet. SIK1 promotes insulin resistance on high fat diet by a cell-autonomous mechanism in skeletal muscle. Our study establishes SIK1 as a promising therapeutic target to improve skeletal muscle insulin sensitivity in obese individuals without deleterious effects on hepatic glucose production. PMID- 26844208 TI - A method for assessing chemically-induced paralysis in headless mosquito larvae. AB - There is a growing interest in studies of mosquito physiology and toxicology due to the heightened need for controlling this group of human disease vectors. In the process of testing a group of polar compounds on mosquito muscles, a novel headless larva bioassay was developed. The heads were removed from fourth instar Aedes aegypti larvae, which permitted access of pharmacological agents to the hemocoel while maintaining larval viability. The method allowed effective quantification of the paralytic actions of water soluble compounds that could not ordinarily penetrate the mosquito larva integument and was more easily performed than injection when studying small, soft-bodied aquatic organisms. The summary of the method is: *Heads of A. aegypti larvae were detached with two pairs of forceps, and the larvae remained responsive for at least 5 h.*The responsiveness of the larvae was assessed by using a microscope to observe movement after the larvae were probed with an insect pin.*Drug effects were quantified using either a binary paralysis determination (paralyzed vs. not paralyzed), or by counting movement units after probing. PMID- 26844206 TI - Incretin-like effects of small molecule trace amine-associated receptor 1 agonists. AB - OBJECTIVE: Type 2 diabetes and obesity are emerging pandemics in the 21st century creating worldwide urgency for the development of novel and safe therapies. We investigated trace amine-associated receptor 1 (TAAR1) as a novel target contributing to the control of glucose homeostasis and body weight. METHODS: We investigated the peripheral human tissue distribution of TAAR1 by immunohistochemistry and tested the effect of a small molecule TAAR1 agonist on insulin secretion in vitro using INS1E cells and human islets and on glucose tolerance in C57Bl6, and db/db mice. Body weight effects were investigated in obese DIO mice. RESULTS: TAAR1 activation by a selective small molecule agonist increased glucose-dependent insulin secretion in INS1E cells and human islets and elevated plasma PYY and GLP-1 levels in mice. In diabetic db/db mice, the TAAR1 agonist normalized glucose excursion during an oral glucose tolerance test. Sub chronic treatment of diet-induced obese (DIO) mice with the TAAR1 agonist resulted in reduced food intake and body weight. Furthermore insulin sensitivity was improved and plasma triglyceride levels and liver triglyceride content were lower than in controls. CONCLUSIONS: We have identified TAAR1 as a novel integrator of metabolic control, which acts on gastrointestinal and pancreatic islet hormone secretion. Thus TAAR1 qualifies as a novel and promising target for the treatment of type 2 diabetes and obesity. PMID- 26844207 TI - EBF2 promotes the recruitment of beige adipocytes in white adipose tissue. AB - OBJECTIVE: The induction of beige/brite adipose cells in white adipose tissue (WAT) is associated with protection against high fat diet-induced obesity and insulin resistance in animals. The helix-loop-helix transcription factor Early B Cell Factor-2 (EBF2) regulates brown adipose tissue development. Here, we asked if EBF2 regulates beige fat cell biogenesis and protects animals against obesity. METHODS: In addition to primary cell culture studies, we used Ebf2 knockout mice and mice overexpressing EBF2 in the adipose tissue to study the necessity and sufficiency of EBF2 to induce beiging in vivo. RESULTS: We found that EBF2 is required for beige adipocyte development in mice. Subcutaneous WAT or primary adipose cell cultures from Ebf2 knockout mice did not induce Uncoupling Protein 1 (UCP1) or a thermogenic program following adrenergic stimulation. Conversely, over-expression of EBF2 in adipocyte cultures induced UCP1 expression and a brown like/beige fat-selective differentiation program. Transgenic expression of Ebf2 in adipose tissues robustly stimulated beige adipocyte development in the WAT of mice, even while housed at thermoneutrality. EBF2 overexpression was sufficient to increase mitochondrial function in WAT and protect animals against high fat diet-induced weight gain. CONCLUSIONS: Taken together, our results demonstrate that EBF2 controls the beiging process and suggest that activation of EBF2 in WAT could be used to reduce obesity. PMID- 26844209 TI - Simple solutions to false results with plate/slide agglutination tests in diagnosis of infectious diseases of man and animals. AB - We have developed a new Superagglutination test for serodiagnosis of infectious diseases. It differs from conventional plate/slide agglutination tests (PAT/SAT) by three additional steps: prior staining of serum antibody by adding a dye and addition of diluted biotinylated antiglobulin and avidin in sequence after mixing the antigen with the test serum. The new steps circumvent the problems of false positive and false negative results of PAT/SAT. In serodiagnosis of brucellosis, Superagglutination test had higher positive predictive value and specificity than Rose Bengal Plate Test (RBPT) and Standard Tube Agglutination Test (STAT) and higher negative predictive value and sensitivity than RBPT, STAT, ELISA and Complement Fixation Test (CFT).*Superagglutination is a simple, accurate and economic screening test for infections.*More specificity, sensitivity, positive & negative predictive value than RBPT, STAT.*More sensitivity, negative predictive value than ELISA and Complement Fixation Test. PMID- 26844210 TI - Extension of the standard addition method by blank addition. AB - Standard addition involves adding varying amounts of the analyte to sample portions of fixed mass or fixed volume and submitting those portions to the sample preparation procedure. After measuring the final extract solutions, the observed signals are linearly regressed on the spiked amounts. The original unknown amount is estimated by the opposite of the abscissa intercept of the fitted straight line [1]. A limitation of this method is that only data points with abscissa values equal to and greater than zero are available so that there is no information on whether linearity holds below the spiking level zero. An approach to overcome this limitation is introduced.*Standard addition is combined with blank addition.*Blank addition means that defined mixtures of blank matrix and sample material are subjected to sample preparation to give final extract solutions.*Equations are presented to estimate the original unknown amount and to calculate the 1-2alpha confidence interval about this estimate using the combined data set. PMID- 26844211 TI - Preparation of inocula for experimental infection of blood with Streptococcus pneumoniae. AB - Experimental infections of either cells or animals require the preparation of good quality inocula. Unfortunately, the important pulmonary pathogen Streptococcus pneumoniae is a fastidious microorganism that suffers an autolysis process when cultured in vitro. Supplementation of Todd-Hewitt broth with a biological buffer (20 mM Tris-HCl, pH = 7.8) promotes a six hours delay in the beginning of the autolysis process. Additional improvements include washing bacteria before freezing, avoiding manipulations after thawing, and the use of glycerol (<18%) as a cryoprotectant, instead of reagents like skimmed milk that may affect cell cultures. With the proposed protocol >70% of the frozen bacteria was viable after 28 weeks at -80 degrees C, and aliquots were highly homogeneous. We have tested their utility in a whole blood infection model and have found that human plasma exhibits a higher microbicidal activity than whole blood, a result that we have not found previously reported. Additionally, we have also observed significant variations in the antimicrobial activity against different strains, which might be related to their virulence.*Media culture buffering extends S. pneumoniae viability for 6 h.*Washing before freezing of single use aliquots minimizes manipulation after thawing.*Experimental infection with the frozen inocula has shown that plasma has higher bactericidal activity than blood. PMID- 26844212 TI - Expression and phosphorylation state analysis of intracellular protein kinases using Multi-PK antibody and Phos-tag SDS-PAGE. AB - Protein kinase expression and activity play important roles in diverse cellular functions through regulation of phosphorylation signaling. The most commonly used tools for detecting the protein kinase are protein kinase-specific antibodies, and phosphorylation site-specific antibodies were used for detecting activated protein kinase. Using these antibodies, only one kinase was analyzed at a time, however, a method for analyzing the expression and activation of a panel of protein kinases in cells is not established. Therefore, we developed a combined method using Multi-PK antibody and Phos-tag SDS-PAGE for profiling the expression and phosphorylation state of intracellular protein kinases. Using the new method, changes in the expression and phosphorylation state of various protein kinases were detected in cells treated with anticancer agent which inhibit multiple tyrosine kinase activities. Therefore, the new method is a useful technique for analysis of intracellular protein kinases.*Multi-PK antibody recognizes a wide variety of protein kinases in various species.*Using Phos-tag SDS-PAGE, phosphorylated proteins are visualized as slower migration bands compared with corresponding non-phosphorylated proteins.*This combined method can be used for detecting changes in the expression and phosphorylation state of various intracellular protein kinases. PMID- 26844214 TI - Asia Pacific Allergy: it's been five years! PMID- 26844213 TI - Cell Fate Decision Making through Oriented Cell Division. AB - The ability to dictate cell fate decisions is critical during animal development. Moreover, faithful execution of this process ensures proper tissue homeostasis throughout adulthood, whereas defects in the molecular machinery involved may contribute to disease. Evolutionarily conserved protein complexes control cell fate decisions across diverse tissues. Maintaining proper daughter cell inheritance patterns of these determinants during mitosis is therefore a fundamental step of the cell fate decision-making process. In this review, we will discuss two key aspects of this fate determinant segregation activity, cortical cell polarity and mitotic spindle orientation, and how they operate together to produce oriented cell divisions that ultimately influence daughter cell fate. Our focus will be directed at the principal underlying molecular mechanisms and the specific cell fate decisions they have been shown to control. PMID- 26844215 TI - Pharmacotherapy in the management of asthma in the elderly: a review of clinical studies. AB - Asthma in the elderly is a disease with emerging concern. Despite some recent advances in our understanding of epidemiology and pathophysiology, there is a considerable lack of clinical evidence specific to elderly patients. Currently available high quality clinical evidence has been mostly obtained from younger adults, but rarely from elderly patients. Under-representation of elderly patients in previous randomized trials may have been due to being, old age, or having comorbidities. Thus, a question may be raised whether current clinical evidence could be well generalized into elderly patients. Further clinical trials should address clinical issues raised in elderly population. In this review, we aimed to overview the efficacy and safety of pharmacological management, and also to summarize the literature relevant to elderly asthma. PMID- 26844216 TI - A stepwise approach in the management of chronic spontaneous urticaria in children. AB - BACKGROUND: There is limited literature in the management of chronic urticaria in children. Treatment algorithms are generally extrapolated from adult studies. OBJECTIVE: Utility of a weight and age-based algorithm for antihistamines in management of chronic spontaneous urticaria (CSU) in childhood. To document associated factors that predict for step of control of CSU and time taken to attain control of symptoms in children. METHODS: A workgroup comprising of allergists, nurses, and pharmacists convened to develop a stepwise treatment algorithm in management of children with CSU. Sequential patients presenting to the paediatric allergy service with CSU were included in this observational, prospective study. RESULTS: Ninety-eight patients were recruited from September 2012 to September 2013. Majority were male, Chinese with median age 4 years 7 months. A third of patients with CSU had a family history of acute urticaria. Ten point two percent had previously resolved CSU, 25.5% had associated angioedema, and 53.1% had a history of atopy. A total of 96.9% of patients achieved control of symptoms, of which 91.8% achieved control with cetirizine. Fifty percent of all the patients were controlled on step 2 or higher. Forty-seven point eight percent of those on step 2 or higher were between 2 to 6 years of age compared to 32.6% and 19.6% who were 6 years and older and lesser than 2 years of age respectively. Eighty percent of those with previously resolved CSU required an increase to step 2 and above to achieve chronic urticaria control. CONCLUSION: We propose a weight- and age-based titration algorithm for different antihistamines for CSU in children using a stepwise approach to achieve control. This algorithm may improve the management and safety profile for paediatric CSU patients and allow for review in a more systematic manner for physicians dealing with CSU in children. PMID- 26844217 TI - Anaphylaxis audit in a busy metropolitan Emergency Department: a review of real life management compared to best practice. AB - BACKGROUND: Deficiencies in anaphylaxis management in Emergency Departments is well recognised despite established guidelines for its treatment. OBJECTIVE: To identify deficiencies in the management of anaphylaxis in a busy metropolitan Emergency Department and determine if an education intervention could correct these. METHODS: Paediatric and adult admissions to the Emergency Department of a busy hospital were tracked over a 10-month period with a targeted educational program being instituted at 5 months. The electronic records were retrospectively reviewed looking for cases of anaphylaxis and milder forms of immediate type allergic reactions presenting with a combination of urticaria and nonairway threatening angioedema. Anaphylaxis presentation was graded using the Brown grading system. Use of all medication during resuscitation was documented. Observation period before discharge and referral to specialist unit for follow-up was noted. RESULTS: In the first 5 months, 38 patients fulfilled our criteria. Three had severe anaphylaxis, 13 had moderately severe anaphylaxis and 12 had urticaria and angioedema without anaphylaxis. Anaphylaxis was not always recognised or graded leading to inappropriate management with adrenaline often being withheld. Promethazine, usually given in parenteral form, was frequently administered. Observation time was often inadequate. Referral to an immunologist was not universally followed through. Following the educational intervention 58 patients fulfilled our criteria over the next 5 months. The appropriate use of adrenaline increased by 21% and the use of sedating antihistamines decreased by 16%, while the number of referrals to an immunologist increased by 24%. There was an 11% reduction in the number of patients who were observed for at least 4 hours. CONCLUSION: A number of deficiencies in the management of anaphylaxis presentations have been identified. Targeted educational activities aimed at the Emergency Department hospital staff may improve outcomes. PMID- 26844219 TI - Stevens-Johnson syndrome and toxic epidermal necrolysis in Dr. Hasan Sadikin General Hospital Bandung, Indonesia from 2009-2013. AB - BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions (SCAR) with high mortality and have a significant public health impact because of high mortality and morbidity. OBJECTIVE: To describe data the epidemiological features, etiology, and treatment of retrospectively reviewed data of all patients with SJS and TEN. METHODS: Retrospective study was conducted in patients with SJS and TEN treated from January 1, 2009 to December 31, 2013 in Dr. Hasan Sadikin General Hospital Bandung, Indonesia. RESULTS: A total of 57 patients were enrolled in the study. Thirty-nine cases of SJS (21 males and 18 females), 7 cases of SJS overlapping TEN (4 males and 3 females), and 11 cases of TEN (5 males and 6 females) were reported. All cases of SJS and TEN were caused by drugs, such as paracetamol (16.56%), carbamazepine (7%), amoxicillin (5.73%), ibuprofen (4.46%), rifampicin (3.18%), and trihexyphenidyl (3.18%). All cases were treated systemically with corticosteroid alone (100%). Seven from 57 patients (12,28%) died; 5 cases developed sepsis and 2 cases developed respiratory failure. The mortality rate was 7.69% in SJS, 0% in SJS/TEN overlap, and 36.36% in TEN. CONCLUSION: The role of systemic corticosteroids in SJS and TEN are still controversial, but with a prompt and earlier treatment reduces mortality and improves outcomes of SJS and TEN patients. PMID- 26844218 TI - Ultrarush schedule of subcutaneous immunotherapy with modified allergen extracts is safe in paediatric age. AB - BACKGROUND: Traditional subcutaneous immunotherapy up dosing with allergenic extracts has been shown to be associated with frequent adverse reactions. In recent studies it has been demonstrated that using modified extracts, namely allergoids, it is a safe and effective procedure particularly on accelerated schedules. However data assessing its safety in paediatric age is scarce. OBJECTIVE: To evaluate the safety profile in paediatric population of using modified allergen extracts, in an ultrarush schedule, to reach the maintenance dose in the first day. METHODS: We included children undergoing treatment with subcutaneous immunotherapy during a five-year period, using modified aeroallergen extracts, depigmented, polymerized with glutaraldehyde and adsorbed on aluminium hydroxide using an ultrarush induction phase. The type of adverse reactions during the ultrarush protocol was recorded. RESULTS: We studied 100 paediatric patients (57 males) with a mean age of 11.6 years (5 to 18 years; standard deviation, 3.3), all with moderate to severe persistent rhinitis, with or without allergic conjunctivitis, asthma and atopic eczema, sensitized to mites and/or pollens. All reached the maintenance dose of 0.5 mL in the first day, except 1 child. During the ultrarush protocol the total number of injections was 199. There were 21 local adverse reactions in 11 patients, 11 immediate and 10 delayed; from those, had clinical relevance 1 immediate and 4 delayed. Systemic reactions were recorded in 2 cases, both immediate and mild. CONCLUSION: The ultrarush protocol, without premedication, was a safe alternative to be used in paediatric age during the induction phase of subcutaneous immunotherapy using allergoid depigmented extracts. PMID- 26844220 TI - Acute and chronic exposure to Tyrophagus putrescentiae induces allergic pulmonary response in a murine model. AB - BACKGROUND: Tyrophagus putrescentiae (Tp) is a source of aeroallergen that causes allergic diseases. OBJECTIVE: To describe an acute and chronic murine model of allergic asthma with Tp extract with no systemic sensitization and no use of adjuvant. METHODS: Mites from dust sample were cultured and a raw extract was produced. Female BALB/c mice (6-8 weeks) were challenged intranasally with Tp extract or Dulbecco's phosphate-buffered saline, for 10 consecutive days (acute protocol) or for 6 weeks (chronic protocol). Twenty-four hours after the last intranasal challenge, bronchoalveolar lavage fluid (BALF) was performed for total and differential cells count, cytokine analysis, and eosinophil peroxidase activity. Lung tissue was also removed for histopathologic analysis. RESULTS: Tp extract has shown a significant increase in total cells count from BALF as well as an increase in absolute eosinophils count, eosinophil peroxidase activity, interleukin (IL)-5 and IL-13 levels, in both acute and chronic protocols. Peribronchovascular infiltrate, goblet cells hyperplasia and collagen deposition were shown in the airways of acute and chronic Tp-exposed mice. CONCLUSION: Our data suggest that the intranasal exposure to Tp extract, with no systemic sensitization and no use of adjuvants, induces a robust allergic inflammation in the lungs of mice, in both acute and chronic models. Our Tp extract seems to be a potent allergen extract which may be used in asthma model studies. PMID- 26844222 TI - Childhood allergic bronchopulmonary aspergillosis presenting as a middle lobe syndrome. AB - Allergic bronchopulmonary aspergillosis (ABPA) is infrequently documented in children with asthma. Although collapse is not uncommon, middle lobe syndrome (MLS) as a presentation of ABPA is rather a rarity. A 9-year-old female child with asthma presented with increase in intensity of symptoms along with a right midzone patchy consolidation on a chest radiograph. In addition, an ill-defined opacity abutting the right cardiac border with loss of cardiac silhouette was noted. A right lateral view confirmed a MLS, which was further corroborated by high resolution computed tomography. Central bronchiectasis was also observed, which prompted a work-up for ABPA. The child met 7/8 major diagnostic criteria for ABPA. She was then initiated on oral prednisolone that resulted in a marked clinical improvement within a fortnight. Radiological clearance occurred at 3 months with inflation of the middle lobe. ABPA presenting with MLS in a child is yet to be reported. A high index of suspicion is required to establish the diagnosis of ABPA in a child presenting with MLS. This would obviate the invasive investigations usually done to ascertain the cause of MLS. PMID- 26844223 TI - Ibuprofen induced Stevens-Johnson syndrome - toxic epidermal necrolysis in Nepal. AB - Despite the fact that any drug can be an impending cause of hypersensitivity reactions, Ibuprofen, an over-the-counter drug used extensively as an analgesic and antipyretic in Asia, is considered to be relatively safe. But herein we report a rare extremely 'rapid onset' occurrence of a severe case of Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in a 22-year-old male, induced by 3 doses of 400 mg of Ibuprofen taken at 8-hour interval for eye pain, probably the first case report of rapid onset of TEN by nonsteroidal antiinflammatory drugs in Nepal. SJS and TEN are idiosyncratic, delayed hypersensitivity inflammatory adverse drug reactions that are severe adverse cutaneous drug reactions which predominantly involve the skin and mucous membranes and are linked with high morbidity and mortality. Nevertheless, removal of ibuprofen and its metabolites with plasma exchange and treatment with antibiotics and intravenous corticosteroids along with supportive therapy improved the course of the disorder. This rare case report addresses the fact that severe hypersensitivity reactions can occur with Ibuprofen, which can be potentially dangerous and life threatening. It is thus important for the clinicians to be alert to such severe hypersensitivity reactions even with drugs which are deemed to be probably safe. PMID- 26844221 TI - Role of bilastine in the management of allergic rhinitis and urticaria: an Asia Pacific consensus statement. AB - The prevalence of allergic diseases is increasing globally, most particularly in middle- to low-income countries. This article examines the burden of allergic rhinitis and chronic urticaria in the Asia-Pacific region, unmet clinical needs, and the potential role of bilastine in the management of these conditions. An International Advisory Group meeting was convened in association with the Asian Pacific Society of Respirology Annual Congress in November 2014, followed by a literature review, and consensus-based outcomes from the meeting and literature review are described. Regional estimates of the prevalence of allergic rhinitis range from 10% to 50%, while little is known regarding the burden of urticaria in the Asia-Pacific region. A survey of allergy patients in the region identified fast, complete, and long-lasting symptom relief as the medication attributes most important to patients. International treatment guidelines for allergic rhinitis and urticaria advocate the first-line use of second-generation, no-sedating H1 antihistamines, such as bilastine, over their first-generation counterparts and a range of these agents are available to Asia-Pacific patients. The newer agents possess many of the properties of an "ideal" antihistamine (once daily administration, rapid and complete symptom relief, limited potential for drug drug interactions, minimal side effects). The burgeoning prevalence of allergic diseases in the Asia-Pacific region and the uncontrolled symptoms that these patients experience demand a new antihistamine that offers the highest number of positive features according to the international guidelines. PMID- 26844224 TI - Clinical Performance and Safety of 108 SpineJack Implantations: 1-Year Results of a Prospective Multicentre Single-Arm Registry Study. AB - This prospective, consecutive, multicentre observational registry aimed to confirm the safety and clinical performance of the SpineJack system for the treatment of vertebral compression fractures (VCF) of traumatic origin. We enrolled 103 patients (median age: 61.6 years) with 108 VCF due to trauma, or traumatic VCF with associated osteoporosis. Primary outcome was back pain intensity (VAS). Secondary outcomes were Oswestry Disability Index (ODI), EuroQol VAS, and analgesic consumption. 48 hours after surgery, a median relative decrease in pain intensity of 81.5% was observed associated with a significant reduction in analgesic intake. Improvements in disability (91.3% decrease in ODI score) and in quality of life (increase 21.1% of EQ-VAS score) were obtained 3 months after surgery. All results were maintained at 12 months. A reduction in the kyphotic angulation was observed postoperatively (-5.4 +/- 6.3 degrees ; p < 0.001), remained at 12 months (-4.4 +/- 6.0 degrees , p = 0.002). No adverse events were implant-related and none required device removal. Three patients (2.9%) experienced procedure-related complications. The overall adjacent fracture rate up to 1 year after surgery was 2.9%. The SpineJack procedure is an effective, low-risk procedure for patients with traumatic VCF allowing a fast and sustained improvement in quality of life over 1 year after surgery. PMID- 26844225 TI - New Trends in Instrumentation and Complex Techniques in Spine Surgery. PMID- 26844227 TI - The Prognosis of IVF in Poor Responders Depending on the Bologna Criteria: A Large Sample Retrospective Study from China. AB - OBJECTIVE: To analyze the treatment outcomes of patients who accepted IVF/ICSI ET, diagnosed POR according to Bologna criteria. STUDY DESIGN: Retrospective cohort study of one reproductive medical center, from 1st Jan., 2009, to 31st Dec., 2014. All patients fulfilled the Bologna criteria and accept IVF/ICSI-ET treatment with stimulation cycle. The main outcome measures were clinical pregnancy rate (CPR) and live birth rate (LBR). RESULTS: There were 5770 eligible cycles included in this study. The incidence of POR was 10.3% (6286/62194). The overall CPR was 18.7%, IR was 11.6%, LBR/ET was 11.5%, and LBR/OPU was 8.3%. The cycle cancellation for no available oocyte or embryo was 4.9% and 18.6%, respectively. The subgroup of younger POR patients got highest CPR and LBR/ET, which decreased while increasing maternal age. Within three attempts, the patients got similar CPR and LBR. CONCLUSION: In conclusion, our study supports the Bologna criteria that defined women with poor IVF outcomes. But those younger than 42 years old with the first 3 attempts of IVF could got acceptable CPR and LBR. PMID- 26844226 TI - After Myocardial Ischemia-Reperfusion, miR-29a, and Let7 Could Affect Apoptosis through Regulating IGF-1. AB - Cardiovascular and cerebrovascular ischemic disease is a large class of diseases that is harmful to human health. The primary treatment for the ischemic disease is to recover the blood perfusion and relieve the tissue hypoxia and the shortage of the nutrients in the supply of nutrients. In recent years, investigations found that IGF-1 has a protective effect on cardiovascular disease, especially in myocardial ischemia-reperfusion injury. Investigation into molecular mechanism of ischemia-reperfusion injury may offer potential targets for the development of novel diagnostic strategies. In this study we defined IGF-1 was differentially expressed in the I/R model of the Mus musculus and IGF-1 was the target gene of miR-29a and Let7f. After ischemia-reperfusion, the expression of miR-29a and Let7f increased, while the expression of IGF-1 decreased significantly in the animal model assay. Further studies have found that IGF-1 could inhibit cell apoptosis signaling pathway, thus protecting the reperfusion injury. These results provide new understanding of ischemia-reperfusion injury, with the hope of offering theoretical support for future therapeutic studies. PMID- 26844228 TI - Effect of Tyrosol and Farnesol on Virulence and Antibiotic Resistance of Clinical Isolates of Pseudomonas aeruginosa. AB - Mixed-species biofilms could create a protected environment that allows for survival to external antimicrobials and allows different bacterial-fungal interactions. Pseudomonas aeruginosa-Candida albicans coexistence is an example for such mixed-species community. Numerous reports demonstrated how P. aeruginosa or its metabolites could influence the growth, morphogenesis, and virulence of C. albicans. In this study, we investigated how the C. albicans quorum sensing compounds, tyrosol and farnesol, might affect Egyptian clinical isolates of P. aeruginosa regarding growth, antibiotic sensitivity, and virulence. We could demonstrate that tyrosol possesses an antibacterial activity against P. aeruginosa (10 uM inhibited more than 50% of growth after 16 h cultivation). Moreover, we could show for the first time that tyrosol strongly inhibits the production of the virulence factors hemolysin and protease in P. aeruginosa, whereas farnesol inhibits, to lower extent, hemolysin production in this bacterial pathogen. Cumulatively, tyrosol is expected to strongly affect P. aeruginosa in mixed microbial biofilm. PMID- 26844229 TI - 15d-PGJ2 Reduced Microglia Activation and Alleviated Neurological Deficit of Ischemic Reperfusion in Diabetic Rat Model. AB - To investigate the effect of PPARgamma agonist 15d-PGJ2 treatment on the microglia activation and neurological deficit of ischemia reperfusion in diabetic rat model, adult Sprague-Dawley rats were sacrificed for the research. The rats were randomly categorized into four groups: (1) sham-operated group; (2) standard ischemia group; (3) diabetic ischemia group; (4) diabetic ischemia group with diabetes and treated with 15d-PGJ2. Compared to the sham-operated group, all the ischemic groups have significantly severer neurological deficits, more TNF-alpha and IL-1 expression, increased labeling of apoptotic cells, increased CD68 positive staining of brain lesion, and increased volume of infarct and cerebral edema in both 24 hours and 7 days after reperfusion. Interestingly, reduced neurological deficits, decreased TNF-alpha and IL-1 expression, less apoptotic cells and CD68 positive staining, and alleviated infarct and cerebral edema volume were observed when 15d-PGJ2 was intraperitoneally injected after reperfusion in diabetic ischemia group, suggesting its neuroprotective role in regulating microglia activation, which may have a therapeutic application in the future. PMID- 26844230 TI - Coupling of the Functional Stability of Rat Myocardium and Activity of Lipid Peroxidation in Combined Development of Postinfarction Remodeling and Diabetes Mellitus. AB - Coupling of the functional stability of rat myocardium and activity of lipid peroxidation processes in combined development of postinfarction remodeling and diabetes mellitus has been studied. The functional stability of myocardium was studied by means of the analysis of inotropic reaction on extrasystolic stimulus, the degree of left ventricular hypertrophy, and the size of scar zone. It was shown that in combined development of postinfarction cardiac remodeling of heart (PICR) with diabetes mellitus (DM) animal body weight decreased in less degree than in diabetic rats. Animals with combined pathology had no heart hypertrophy. The amplitude of extrasystolic contractions in rats with PICR combined with DM had no differences compared to the control group. In myocardium of rats with PICR combined with DM postextrasystolic potentiation was observed in contrast with the rats with PICR alone. The rats with combined pathology had the decreased value of TBA-active products. Thus, the results of study showed that induction of DM on the stage of the development of postinfarction remodeling increases adaptive ability of myocardium. It is manifested in inhibition of increase of LPO processes activity and maintaining of force-interval reactions of myocardium connected with calcium transport systems of sarcoplasmic reticulum of cardiomyocytes. PMID- 26844232 TI - Advances in Computational Immunology. PMID- 26844231 TI - Prevalence of Urinary Tract Infection and Antimicrobial Susceptibility among Diabetic Patients with Controlled and Uncontrolled Glycemia in Kuwait. AB - Diabetic patients have higher risk of urinary tract infection (UTI). In the present study, we investigated the impact of glycemic control in diabetic patients on UTI prevalence, type of strains, and their antimicrobial drugs susceptibility. This study was conducted on urine samples from 722 adult diabetic patients from which 252 (35%) samples were positive for uropathogens. Most UTI cases occurred in the uncontrolled glycemic group (197 patients) versus 55 patients with controlled glycemia. Higher glycemic levels were measured in uncontrolled glycemia group (HbA1c = 8.3 +/- 1.5 and 5.4 +/- 0.4, resp., P < 0.0001). Females showed much higher prevalence of UTI than males in both glycemic groups (88.5% and 11.5%, resp., P < 0.0001). In the uncontrolled glycemia group 90.9% of the UTI cases happened at ages above 40 years and a clear correlation was obtained between patient age ranges and number of UTI cases (r = 0.94; P = 0.017), whereas in the group with controlled glycemia no trend was observed. Escherichia coli was the predominant uropathogen followed by Klebsiella pneumoniae and they were together involved in 76.2% of UTI cases. Those species were similarly present in both diabetic groups and displayed comparable antibiotic resistance pattern. These results highlight the importance of controlling glycemia in diabetic patients to reduce the UTI regardless of age and gender. PMID- 26844233 TI - Mutanome Engineered RNA Immunotherapy: Towards Patient-Centered Tumor Vaccination. AB - Advances in nucleic acid sequencing technologies have revolutionized the field of genomics, allowing the efficient targeting of mutated neoantigens for personalized cancer vaccination. Due to their absence during negative selection of T cells and their lack of expression in healthy tissue, tumor mutations are considered as optimal targets for cancer immunotherapy. Preclinical and early clinical data suggest that synthetic mRNA can serve as potent drug format allowing the cost efficient production of highly efficient vaccines in a timely manner. In this review, we describe a process, which integrates next generation sequencing based cancer mutanome mapping, in silico target selection and prioritization approaches, and mRNA vaccine manufacturing and delivery into a process we refer to as MERIT (mutanome engineered RNA immunotherapy). PMID- 26844234 TI - mHealth Tool for Alcohol Use Disorders Among Latinos in Emergency Department. AB - Latino drinkers experience a disparate number of negative health and social consequences. Emergency Department Alcohol Screening Brief Intervention and Referral to Treatment (ED-SBIRT) is viable and effective at reducing harmful and hazardous drinking. However, barriers (e.g. readily available language translators, provider time burden, resources) to broad implementation remain and account for a major lag in adherence to national guidelines. We describe our approach to the design of a patient-centered bilingual Web-based mobile health ED SBIRT App that could be integrated into a clinically complex ED environment and used regularly to provide ED-SBIRT for Spanish speaking patients. PMID- 26844235 TI - Volume estimation of multidensity nodules with thoracic computed tomography. AB - This work focuses on volume estimation of "multidensity" lung nodules in a phantom computed tomography study. Eight objects were manufactured by enclosing spherical cores within larger spheres of double the diameter but with a different density. Different combinations of outer-shell/inner-core diameters and densities were created. The nodules were placed within an anthropomorphic phantom and scanned with various acquisition and reconstruction parameters. The volumes of the entire multidensity object as well as the inner core of the object were estimated using a model-based volume estimator. Results showed percent volume bias across all nodules and imaging protocols with slice thicknesses [Formula: see text] ranging from [Formula: see text] to 6.6% for the entire object (standard deviation ranged from 1.5% to 7.6%), and within [Formula: see text] to 5.7% for the inner-core measurement (standard deviation ranged from 2.0% to 17.7%). Overall, the estimation error was larger for the inner-core measurements, which was expected due to the smaller size of the core. Reconstructed slice thickness was found to substantially affect volumetric error for both tasks; exposure and reconstruction kernel were not. These findings provide information for understanding uncertainty in volumetry of nodules that include multiple densities such as ground glass opacities with a solid component. PMID- 26844239 TI - Response to neuropeptide Y: Biomarker and intervention for surgical recovery. PMID- 26844237 TI - Negative allosteric modulation of the mGlu7 receptor reduces visceral hypersensitivity in a stress-sensitive rat strain. AB - Glutamate, the main excitatory neurotransmitter in the central nervous system, exerts its effect through ionotropic and metabotropic receptors. Of these, group III mGlu receptors (mGlu 4, 6, 7, 8) are among the least studied due to a lack of pharmacological tools. mGlu7 receptors, the most highly conserved isoform, are abundantly distributed in the brain, especially in regions, such as the amygdala, known to be crucial for the emotional processing of painful stimuli. Visceral hypersensitivity is a poorly understood phenomenon manifesting as an increased sensitivity to visceral stimuli. Glutamate has long been associated with somatic pain processing leading us to postulate that crossover may exist between these two modalities. Moreover, stress has been shown to exacerbate visceral pain. ADX71743 is a novel, centrally penetrant, negative allosteric modulator of mGlu7 receptors. Thus, we used this tool to explore the possible involvement of this receptor in the mediation of visceral pain in a stress-sensitive model of visceral hypersensitivity, namely the Wistar Kyoto (WKY) rat. ADX71743 reduced visceral hypersensitivity in the WKY rat as exhibited by increased visceral sensitivity threshold with concomitant reductions in total number of pain behaviours. Moreover, AD71743 increased total distance and distance travelled in the inner zone of the open field. These findings show, for what is to our knowledge, the first time, that mGlu7 receptor signalling plays a role in visceral pain processing. Thus, negative modulation of the mGlu7 receptor may be a plausible target for the amelioration of stress-induced visceral pain where there is a large unmet medical need. PMID- 26844238 TI - Summary cortisol reactivity indicators: Interrelations and meaning. AB - Research on the hypothalamic pituitary adrenal (HPA) axis has involved a proliferation of cortisol indices. We surveyed recently published HPA-related articles and identified 15 such indices. We sought to clarify their biometric properties, specifically, how they interrelate and what they mean, because such information is rarely offered in the articles themselves. In the present article, the primary samples consist of community mothers and their infants (N = 297), who participated in two challenges, the Toy Frustration Paradigm and the Strange Situation Procedure. We sought to cross-validate findings from each of these samples against the other, and also against a clinically depressed sample (N = 48) and a sample of healthy older adults (N = 51) who participated in the Trier Social Stress Test. Cortisol was collected from all participants once before and twice after the challenges. These heterogenous samples were chosen to obtain the greatest possible range in cortisol levels and stress response regulation. Using these data, we computed the 15 summary cortisol indices identified in our literature survey. We assessed inter-relations amongst indices and determined their underlying dimensions via principal component analysis (PCA). The PCAs consistently extracted two components, accounting for 79%-93% of the variance. These components represent "total cortisol production" and "change in cortisol levels." The components were highly congruent across challenge, time, and sample. High variable loadings and explained factor variance suggest that all indices represent their underlying dimensions very well. Thus the abundance of summary cortisol indices currently represented in the literature appears superfluous. PMID- 26844240 TI - Neuropeptide Y: Biomarker and intervention for surgical recovery. PMID- 26844241 TI - Biomarkers of post-deployment resilience among military service members. AB - The development of PTSD after military deployment is influenced by a combination of biopsychosocial risk and resilience factors. In particular, physiological factors may mark risk for symptom progression or resiliency. Research in civilian populations suggests elevated catecholamines after trauma are associated with PTSD months following the trauma. However, less is known regarding physiological markers of PTSD resilience among post-deployment service members (SM). We therefore assessed whether catecholamines obtained shortly after deployment were associated with combat-related PTSD symptoms three months later. Eighty-seven SMs completed the Clinician-Administered PTSD Scale for DSM-IV and blood draws within two months after return from deployment to Iraq or Afghanistan ("Time 1" or "T1") and three months later ("Time 2" or "T2"). Linear regression analyses demonstrated that lower norepinephrine at T1 was associated with lower PTSD symptoms at T2. In particular, T1 norepinephrine was positively associated with T2 symptom intensity and avoidance symptoms. The present findings represent a biologically-informed method of assessing PTSD resilience after deployment, which may aid clinicians in providing tailored treatments for those in the greatest need. Further research is needed to validate these findings and incorporate physiological measures within an assessment battery. PMID- 26844236 TI - Stress as a one-armed bandit: Differential effects of stress paradigms on the morphology, neurochemistry and behavior in the rodent amygdala. AB - Neuroplasticity may be defined as the ability of the central nervous system (CNS) to respond to changes in the internal and external environment and it is well established that some stimuli have the ability to facilitate or impair neuroplasticity depending on the pre-existing milieu. A classic example of a stimulus that can both facilitate and impair neuroplasticity is stress. Indeed, the ability of CNS to respond to acute stress is often dependent upon the prior stress history of the individual. While responses to acute stress are often viewed as adaptive in nature, stress reactivity in subjects with prior chronic stress experiences are often linked to neuropsychiatric disorders, including major depressive disorder, post-traumatic stress disorder (PTSD) and anxiety. In rodent studies, chronic stress exposure produces structural and functional alterations in the hippocampus and medial prefrontal cortex that are consistent across different types of stress paradigms. Conversely, the amygdala appears to exhibit differential structural and functional responses to stress that are dependent on a variety of factors, including the type of stressor performed and the duration of the stress paradigm. This is most evident in output measures including morphological analysis of amygdala neurons, measurement of glutamatergic tone in amygdalar subdivisions and the analysis of amygdala-centric behaviors. Accordingly, this review will provide an overview of the effects of stress on the structural and functional plasticity of the rodent amygdala, especially in relation to the differential effects of repeated or chronic stress paradigms on dendritic architecture, neurochemistry of the glutamatergic system and behavior. PMID- 26844242 TI - BA11 FKBP5 expression levels correlate with dendritic spine density in postmortem PTSD and controls. AB - Genetic variants of the immunophilin FKBP5 have been implicated in susceptibility to post-traumatic stress disorder (PTSD) and other stress-related disorders. We examined the relationship between mushroom, stubby, thin and filopodial spine densities measured with Golgi staining and FKBP5 gene expression in the medial orbitofrontal cortex (BA11) in individuals diagnosed with PTSD and normal controls (n = 8/8). ANCOVA revealed PTSD cases had a significantly elevated density of stubby spines (29%, P < 0.037) and a trend for a reduction in mushroom spine density (25%, p < 0.082). Levels of FKBP5 mRNA were marginally elevated in the PTSD cases (z = 1.94, p = 0.053) and levels correlated inversely with mushroom (Spearman's rho = -0.83, p < 0.001) and overall spine density (rho = 0.75, p < 0.002) and directly with stubby spine density (rho = 0.55, p < 0.027). These data suggest that FKBP5 may participate in a cellular pathway modulating neuronal spine density changes in the brain, and that this pathway may be dysregulated in PTSD. PMID- 26844243 TI - Paraquat and psychological stressor interactions as pertains to Parkinsonian co morbidity. AB - A number of epidemiological and experimental studies have implicated the non selective herbicide, paraquat, in the development of sporadic Parkinson's disease (PD). While preclinical research has focused mainly on elucidating the nigrostriatal effects of paraquat, relatively little data are available concerning non-motor brain systems and inflammatory immune processes (which have been implicated in PD). Hence, in the present study, we sought to take a multi system approach to characterize the influence of paraquat upon extra nigrostriatal brain regions, as well ascertain whether the impact of the pesticide might be enhanced in the context of chronic intermittent stressor exposure. Our findings support the contention that paraquat itself acted as a systemic stressor, with the pesticide increasing plasma corticosterone, as well as altering neurochemical activity in the locus coeruleus, paraventricular nucleus of the hypothalamus, nucleus accumbens, dorsal striatum, and central amygdala. However, with the important exception striatal dopamine turnover, the stressor treatment did not further augment these effects. Additionally, paraquat altered inter-cytokine correlations and, to a lesser extent, circulating cytokine levels, and concomitant stress exposure modulated some of these effects. Finally, paraquat provoked significant (albeit modest) reductions of sucrose preference and weight gain, hinting at possible anhendonic-like or sickness responses. These data suggest that, in addition to being a well known oxidative stress generator, paraquat can act as a systemic stressor affecting hormonal and neurochemical activity, but largely not interacting with a concomitant stressor regimen. PMID- 26844244 TI - Maternal restraint stress delays maturation of cation-chloride cotransporters and GABAA receptor subunits in the hippocampus of rat pups at puberty. AB - The GABAergic synapse undergoes structural and functional maturation during early brain development. Maternal stress alters GABAergic synapses in the pup's brain that are associated with the pathophysiology of neuropsychiatric disorders in adults; however, the mechanism for this is still unclear. In this study, we examined the effects of maternal restraint stress on the development of Cation Chloride Cotransporters (CCCs) and the GABAA receptor alpha1 and alpha5 subunits in the hippocampus of rat pups at different postnatal ages. Our results demonstrate that maternal restraint stress induces a transient but significant increase in the level of NKCC1 (Sodium-Potassium Chloride Cotransporter 1) only at P14, followed by a brief, yet significant increase in the level of KCC2 (Potassium-Chloride Cotransporter 2) at P21, which then decreases from P28 until P40. Thus, maternal stress alters NKCC1 and KCC2 ratio in the hippocampus of rat pups, especially during P14 to P28. Maternal restraint stress also caused biphasic changes in the level of GABAA receptor subunits in the pup's hippocampus. GABAA receptor alpha1 subunit gradually increased at P14 then decreased thereafter. On the contrary, GABAA receptor alpha5 subunit showed a transient decrease followed by a long-term increase from P21 until P40. Altogether, our study suggested that the maternal restraint stress might delay maturation of the GABAergic system by altering the expression of NKCC1, KCC2 and GABAA receptor alpha1 and alpha5 subunits in the hippocampus of rat pups. These changes demonstrate the dysregulation of inhibitory neurotransmission during early life, which may underlie the pathogenesis of psychiatric diseases at adolescence. PMID- 26844246 TI - Corticosterone exposure augments sensitivity to the behavioral and neuroplastic effects of fluoxetine in C57BL/6 mice. AB - Both genetic background and pre-existing stress play critical roles in the effects of antidepressant drugs. The current studies showed this principal by demonstrating that exposure to the stress hormone corticosterone (CORT) allowed behavioral and neurogenic effects to emerge following chronic treatment with fluoxetine of C57BL/6 mice, a strain ordinarily resistant to these effects. Adult male mice were implanted subcutaneously with 21-day slow-release CORT pellets (10 mg) or placebo and then co-treated with 5 mg/kg fluoxetine (b.i.d., i.p.) or saline for 14 days. Animals were then assessed for approach behavior in the novelty-induced hypophagia (NIH) test, hippocampal cell proliferation, corticosteroid receptor expression, and CORT plasma levels. Co-treatment of CORT with fluoxetine significantly reduced approach behavior in the novel environment of the NIH test and increased hippocampal cell proliferation whereas fluoxetine given alone was ineffective. CORT given alone did not alter approach behavior in the novel environment and caused a smaller increase of cell proliferation. The CORT effect was blocked by adrenalectomy and was likely due to increased adrenal feedback. Cell proliferation in CORT-treated animals was associated with reduced mineralocorticoid, but not glucocorticoid, receptor mRNA expression. Although the pellets were advertised to release CORT for 21 days, plasma CORT levels were increased at 1 day after implantation but were not sustained when measured at 7 days or longer intervals. Nevertheless, the transient CORT increase was sufficient to induce long-lasting behavioral and molecular changes when followed by fluoxetine treatment. These studies warrant further investigation into the role of glucocorticoids and environmental stress as adjunctive facilitators of the response to antidepressants, especially for treatment-resistant patients. PMID- 26844245 TI - Alterations in neuronal morphology in infralimbic cortex predict resistance to fear extinction following acute stress. AB - Dysfunction in corticolimbic circuits that mediate the extinction of learned fear responses is thought to underlie the perseveration of fear in stress-related psychopathologies, including post-traumatic stress disorder. Chronic stress produces dendritic hypertrophy in basolateral amygdala (BLA) and dendritic hypotrophy in medial prefrontal cortex, whereas acute stress leads to hypotrophy in both BLA and prelimbic cortex. Additionally, both chronic and acute stress impair extinction retrieval. Here, we examined the effects of a single elevated platform stress on extinction learning and dendritic morphology in infralimbic cortex, a region considered to be critical for extinction. Acute stress produced resistance to extinction, as well as dendritic retraction in infralimbic cortex. Spine density on apical and basilar terminal branches was unaffected by stress. However, animals that underwent conditioning and extinction had decreased spine density on apical terminal branches. Thus, whereas dendritic morphology in infralimbic cortex appears to be particularly sensitive to stress, changes in spines may more sensitively reflect learning. Further, in stressed rats that underwent conditioning and extinction, the level of extinction learning was correlated with spine densities, in that rats with poorer extinction retrieval had more immature spines and fewer thin spines than rats with better extinction retrieval, suggesting that stress may have impaired learning-related spine plasticity. These results may have implications for understanding the role of medial prefrontal cortex in learning deficits associated with stress-related pathologies. PMID- 26844247 TI - PCSK9 Inhibitors: What Lies Beyond Monoclonal Antibodies? PMID- 26844248 TI - The Action Duchenne 13th International Annual Conference, November 6-7, 2015, London, UK. PMID- 26844250 TI - The Influence of Brain State on Functional Connectivity in Autism. PMID- 26844249 TI - Perspectives on the Evolution of Stem Cell Therapy for Heart Failure. PMID- 26844251 TI - Do We Have a Channel Solution for ALS? PMID- 26844252 TI - Penetrating enemy territory: Soluble PCNA-peptides stress out MYCN-overexpressing neuroblastomas. PMID- 26844253 TI - Tuning WNT-beta-catenin signaling via BCL9 proteins for targeting colorectal cancer cells. PMID- 26844254 TI - PP2A Level in Colorectal Cancer Cells Predicts the Response of p38 Targeted Therapy. PMID- 26844255 TI - Distinct Genomic Alterations in Prostate Tumors from African American Men. PMID- 26844256 TI - Radiation Induced Lymphocyte Apoptosis: An Effective Way of "Tailoring" Radiotherapy to the Right Patients Only? PMID- 26844257 TI - Organic Pollutants and Telomere Length: A New Facet of Carcinogenesis. PMID- 26844258 TI - Polychlorinated Biphenyls and Cancer: Are Telomeres to Blame? PMID- 26844259 TI - Familial Pancreatic Cancer: To Screen or not to Screen? PMID- 26844260 TI - Alcohol Misuse and Pancreatitis: A Lesson from Meta-Analysis. PMID- 26844261 TI - Exercise Makes More than an Energy Deficit: Toward Improved Protocols for the Management of Obesity? PMID- 26844262 TI - Genetic Susceptibility to Oxidative Stress and Cardiovascular Disease. PMID- 26844263 TI - Intestinal Alkaline Phosphatase in Stool: A Novel Biomarker for Metabolic Diseases. PMID- 26844264 TI - Using the Tools we Have: Low-efficacy Vaccines and HIV. PMID- 26844265 TI - Beyond Biology: Impact of Center- and Country-specific Economic Factors on Outcomes After Hematopoietic Cell Transplantation. PMID- 26844266 TI - The Evolution of the Stem Cell Theory for Heart Failure. AB - Various stem cell-based approaches for cardiac repair have achieved encouraging results in animal experiments, often leading to their rapid proceeding to clinical testing. However, freewheeling evolutionary developments of the stem cell theory might lead to dystopian scenarios where heterogeneous sources of therapeutic cells could promote mixed clinical outcomes in un-stratified patient populations. This review focuses on the lessons that should be learnt from the first generation of stem cell-based strategies and emphasizes the absolute requirement to better understand the basic mechanisms of stem cell biology and cardiogenesis. We will also discuss about the unexpected "big bang" in the stem cell theory, "blasting" the therapeutic cells to their unchallenged ability to release paracrine factors such as extracellular membrane vesicles. Paradoxically, the natural evolution of the stem cell theory for cardiac regeneration may end with the development of cell-free strategies with multiple cellular targets including cardiomyocytes but also other infiltrating or resident cardiac cells. PMID- 26844267 TI - Muscle A-Kinase Anchoring Protein-alpha is an Injury-Specific Signaling Scaffold Required for Neurotrophic- and Cyclic Adenosine Monophosphate-Mediated Survival. AB - Neurotrophic factor and cAMP-dependent signaling promote the survival and neurite outgrowth of retinal ganglion cells (RGCs) after injury. However, the mechanisms conferring neuroprotection and neuroregeneration downstream to these signals are unclear. We now reveal that the scaffold protein muscle A-kinase anchoring protein-alpha (mAKAPalpha) is required for the survival and axon growth of cultured primary RGCs. Although genetic deletion of mAKAPalpha early in prenatal RGC development did not affect RGC survival into adulthood, nor promoted the death of RGCs in the uninjured adult retina, loss of mAKAPalpha in the adult increased RGC death after optic nerve crush. Importantly, mAKAPalpha was required for the neuroprotective effects of brain-derived neurotrophic factor and cyclic adenosine-monophosphate (cAMP) after injury. These results identify mAKAPalpha as a scaffold for signaling in the stressed neuron that is required for RGC neuroprotection after optic nerve injury. PMID- 26844269 TI - State-Dependent Differences in Functional Connectivity in Young Children With Autism Spectrum Disorder. AB - BACKGROUND: While there is increasing evidence of altered brain connectivity in autism, the degree and direction of these alterations in connectivity and their uniqueness to autism has not been established. The aim of the present study was to compare connectivity in children with autism to that of typically developing controls and children with developmental delay without autism. METHODS: We assessed EEG spectral power, coherence, phase lag, Pearson and partial correlations, and epileptiform activity during the awake, slow wave sleep, and REM sleep states in 137 children aged 2 to 6 years with autism (n = 87), developmental delay without autism (n = 21), or typical development (n = 29). FINDINGS: We found that brain connectivity, as measured by coherence, phase lag, and Pearson and partial correlations distinguished children with autism from both neurotypical and developmentally delayed children. In general, children with autism had increased coherence which was most prominent during slow wave sleep. INTERPRETATION: Functional connectivity is distinctly different in children with autism compared to samples with typical development and developmental delay without autism. Differences in connectivity in autism are state and region related. In this study, children with autism were characterized by a dynamically evolving pattern of altered connectivity. PMID- 26844268 TI - White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease. AB - White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical. PMID- 26844270 TI - Flecainide in Amyotrophic Lateral Sclerosis as a Neuroprotective Strategy (FANS): A Randomized Placebo-Controlled Trial. AB - BACKGROUND: Abnormalities in membrane excitability and Na(+) channel function are characteristic of amyotrophic lateral sclerosis (ALS). We aimed to examine the neuroprotective potential, safety and tolerability of the Na(+) channel blocker and membrane stabiliser flecainide in ALS. METHODS: A double-blind, placebo controlled, randomised clinical trial of flecainide (200 mg/day) for 32-weeks with a 12-week lead-in phase was conducted in participants with probable or definite ALS recruited from multiple Australian centres (ANZCT Registry number ACTRN12608000338369). Patients were reviewed by a cardiologist to rule out cardiac contraindications. Participants were randomly assigned (1:1) to flecainide or placebo using stratified permuted blocks by a central pharmacy. The primary outcome measure was the slope of decline of the ALS Functional Rating Scale-revised (ALS FRS-r) during the treatment period. FINDINGS: Between March 11, 2008 and July 1, 2010, 67 patients were screened, 54 of whom were randomly assigned to receive flecainide (26 patients) or placebo (28 patients). Four patients in the flecainide group and three patients in the placebo group withdrew from the study. One patient in the flecainide group died during the study, attributed to disease progression. Flecainide was generally well tolerated, with no serious adverse events reported in either group. There was no significant difference in the rate of decline in the primary outcome measure ALS-FRS-r between placebo and flecainide treated patients (Flecainide 0.65 [95% CI 0.49 to 0.98]; Placebo 0.81 [0.49 to 2.12] P = 0.50). However, the rate of decline of the neurophysiological index was significantly reduced in the flecainide group (Flecainide 0.06 [0.01 to 0.11]; Placebo 0.14 [0.09 to 0.19], P = 0.02). Placebo treated patients demonstrated greater CMAP amplitude reduction during the course of the study in the subset of patients with a reduced baseline CMAP amplitude (Flecainide: - 15 +/- 12%; Placebo - 59 +/- 12%; P = 0.03). Flecainide-treated patients maintained stabilized peripheral axonal excitability over the study compared to placebo. INTERPRETATION: This pilot study indicated that flecainide was safe and potentially biologically effective in ALS. There was evidence that flecainide stabilized peripheral axonal membrane function in ALS. While the study was not powered to detect evidence of benefit of flecainide on ALS-FRS-r decline, further studies may demonstrate clinical efficacy of flecainide in ALS. PMID- 26844271 TI - The Mechanism by Which MYCN Amplification Confers an Enhanced Sensitivity to a PCNA-Derived Cell Permeable Peptide in Neuroblastoma Cells. AB - Dysregulated expression of MYC family genes is a hallmark of many malignancies. Unfortunately, these proteins are not amenable to blockade by small molecules or protein-based therapeutic agents. Therefore, we must find alternative approaches to target MYC-driven cancers. Amplification of MYCN, a MYC family member, predicts high-risk neuroblastoma (NB) disease. We have shown that R9-caPep blocks the interaction of PCNA with its binding partners and selectively kills human NB cells, especially those with MYCN amplification, and we now show the mechanism. We found elevated levels of DNA replication stress in MYCN-amplified NB cells. R9 caPep exacerbated DNA replication stress in MYCN-amplified NB cells and NB cells with an augmented level of MYC by interfering with DNA replication fork extension, leading to Chk1 dependence and susceptibility to Chk1 inhibition. We describe how these effects may be exploited for treating NB. PMID- 26844272 TI - BCL9/9L-beta-catenin Signaling is Associated With Poor Outcome in Colorectal Cancer. AB - BCL9/9L proteins enhance the transcriptional output of the beta-catenin/TCF transcriptional complex and contribute critically to upholding the high WNT signaling level required for stemness maintenance in the intestinal epithelium. Here we show that a BCL9/9L-dependent gene signature derived from independent mouse colorectal cancer (CRC) models unprecedentedly separates patient subgroups with regard to progression free and overall survival. We found that this effect was by and large attributable to stemness related gene sets. Remarkably, this signature proved associated with recently described poor prognosis CRC subtypes exhibiting high stemness and/or epithelial-to-mesenchymal transition (EMT) traits. Consistent with the notion that high WNT signaling is required for stemness maintenance, ablating Bcl9/9l-beta-catenin in murine oncogenic intestinal organoids provoked their differentiation and completely abrogated their tumorigenicity, while not affecting their proliferation. Therapeutic strategies aimed at targeting WNT responses may be limited by intestinal toxicity. Our findings suggest that attenuating WNT signaling to an extent that affects stemness maintenance without disturbing intestinal renewal might be well tolerated and prove sufficient to reduce CRC recurrence and dramatically improve disease outcome. PMID- 26844273 TI - PP2AC Level Determines Differential Programming of p38-TSC-mTOR Signaling and Therapeutic Response to p38-Targeted Therapy in Colorectal Cancer. AB - The p38 MAP kinase is a promising cancer drug target but its therapeutic effect is not fully understood. Here we report that the response of colorectal cancer (CRC) to p38 inhibitors (p38i) is highly variable: while p38i induces regression of one subgroup of CRCs, it stimulates growth of another subgroup. We further show that PP2AC is differentially expressed in the two different CRC subgroups, which determines the programing of p38-TSC-mTORC1 signaling through differential TSC2 phosphorylation at S664, 1254 and 1798, and the antitumor activity by p38i. Remarkably, modulation of PP2AC level is sufficient to reprogram p38-to-mTORC1 signaling and antitumor response. PP2AC expression accurately predicts therapeutic response to p38i in several CRC models, including a large cohort of patient-derived xenografts (PDXs). Moreover, we demonstrate that combination of p38 and mTOR kinase inhibitors effectively overcomes resistance to either inhibitor in single agent therapy. These results demonstrate that alternative routing of signal transduction underlies differential response to p38 and mTOR targeted therapies. The biomarker-guided therapeutic strategies described herein provide a compelling reason for testing in metastatic CRC patients who suffer very poor prognosis due to lack of efficacious drug therapies. PMID- 26844274 TI - A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men. AB - Evaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP) incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA) and Caucasian American (CA) CaP genomes. We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients). Notably, carriers of this deletion experienced more rapid disease progression. In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somatic mutations in CaP across ancestral groups, which have implications for precision medicine strategies. PMID- 26844275 TI - Radiation-induced CD8 T-lymphocyte Apoptosis as a Predictor of Breast Fibrosis After Radiotherapy: Results of the Prospective Multicenter French Trial. AB - BACKGROUND: Monocentric cohorts suggested that radiation-induced CD8 T-lymphocyte apoptosis (RILA) can predict late toxicity after curative intent radiotherapy (RT). We assessed the role of RILA as a predictor of breast fibrosis (bf +) after adjuvant breast RT in a prospective multicenter trial. METHODS: A total of 502 breast-cancer patients (pts) treated by conservative surgery and adjuvant RT were recruited at ten centers. RILA was assessed before RT by flow cytometry. Impact of RILA on bf + (primary endpoint) or relapse was assessed using a competing risk method. Receiver-operator characteristic (ROC) curve analyses were also performed in intention to treat. This study is registered with ClinicalTrials.gov, number NCT00893035 and final analyses are presented here. FINDINGS: Four hundred and fifty-six pts (90.8%) were included in the final analysis. One hundred and eight pts (23.7%) received whole breast and node irradiation. A boost dose of 10-16 Gy was delivered in 449 pts (98.5%). Adjuvant hormonotherapy was administered to 349 pts (76.5%). With a median follow-up of 38.6 months, grade >= 2 bf + was observed in 64 pts (14%). A decreased incidence of grade >= 2 bf + was observed for increasing values of RILA (p = 0.012). No grade 3 bf + was observed for patients with RILA >= 12%. The area under the ROC curve was 0.62. For cut-off values of RILA >= 20% and < 12%, sensitivity and specificity were 80% and 34%, 56% and 67%, respectively. Negative predictive value for grade >= 2 bf + was equal to 91% for RILA >= 20% and positive predictive value was equal to 22% for RILA < 12% where the overall prevalence of grade >= 2 bf + was estimated at 14%. A significant decrease in the risk of grade >= 2 bf + was found if patients had no adjuvant hormonotherapy (sHR = 0.31, p = 0.007) and presented a RILA >= 12% (sHR = 0.45, p = 0.002). INTERPRETATION: RILA significantly predicts the risk of breast fibrosis. This study validates the use of RILA as a rapid screening test before RT delivery and will change definitely our daily clinical practice in radiation oncology. FUNDING: The French National Cancer Institute (INCa) through the "Program Hospitalier de Recherche Clinique (PHRC)". PMID- 26844276 TI - Polychlorinated Biphenyls and Leukocyte Telomere Length: An Analysis of NHANES 1999-2002. AB - Polychlorinated biphenyls (PCBs) induce the expression of the proto-oncogene c myc which has a role in cellular growth and proliferation programs. The c-myc up regulates the telomerase reverse transcriptase which adds the telomeres repeating sequences to the chromosomal ends to compensate for the progressive loss of telomeric sequence. We performed multivariate linear regression to analyze the association of PCBs, polychlorinated dibenzo-p-dioxins, and 1,2,3,4,6,7,8 heptachlorodibenzofuran with leukocyte telomere length (LTL) in the adult population (n = 2413) of the National Health and Nutrition Examination Survey 1999-2002. LTL was natural log-transformed and the results were re-transformed and presented as percent differences. Individuals in the 3rd and 4th quartiles of the sum of PCBs were associated with 8.33% (95% CI: 4.08-13.88) and 11.63% (95% CI: 6.18-17.35) longer LTLs, respectively, compared with the lowest quartile, with evidence of a dose-response relationship (p-trend < 0.01). The association of the sum PCBs with longer LTL was found in both sexes. Additionally, 1,2,3,4,6,7,8-heptachlorodibenzofuran and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin were associated with longer LTL. The age independent association between longer LTL and environmental exposures to PCBs, 1,2,3,4,6,7,8-heptachlorodibenzofuran and 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin may support a role as tumor promoter of these compounds. Further studies to evaluate the effect of these compounds on LTL are needed to more fully understand the implications of our finding. PMID- 26844277 TI - Screening for Pancreatic Adenocarcinoma in BRCA2 Mutation Carriers: Results of a Disease Simulation Model. AB - BACKGROUND: BRCA2 mutation carriers are at increased risk for multiple cancers including pancreatic adenocarcinoma (PAC). Our goal was to compare the effectiveness of different PAC screening strategies in BRCA2 mutation carriers, from the standpoint of life expectancy. METHODS: A previously published Markov model of PAC was updated and extended to incorporate key aspects of BRCA2 mutation carrier status, including competing risks of breast- and ovarian-cancer specific mortality. BRCA2 mutation carriers were modeled and analyzed as the primary cohort for the analysis. Additional higher risk BRCA2 cohorts that were stratified according to the number of first-degree relatives (FDRs) with PAC were also analyzed. For each cohort, one-time screening and annual screening were evaluated, with screening starting at age 50 in both strategies. The primary outcome was net gain in life expectancy (LE) compared to no screening. Sensitivity analysis was performed on key model parameters, including surgical mortality and MRI test performance. FINDINGS: One-time screening at age 50 resulted in a LE gain of 3.9 days for the primary BRCA2 cohort, and a gain of 5.8 days for those with BRCA2 and one FDR. Annual screening resulted in LE loss of 12.9 days for the primary cohort and 1.3 days for BRCA2 carriers with 1 FDR, but resulted in 20.6 days gained for carriers with 2 FDRs and 260 days gained for those with 3 FDRs. For patients with >= 3 FDRs, annual screening starting at an earlier age (i.e. 35-40) was optimal. INTERPRETATION: Among BRCA2 mutation carriers, aggressive screening regimens may be ineffective unless additional indicators of elevated risk (e.g., 2 or more FDRs) are present. More clinical studies are needed to confirm these findings. FUNDING: American Cancer Society - New England Division - Ellison Foundation Research Scholar Grant (RSG-15-129-01 CPHPS). PMID- 26844279 TI - Alcohol Consumption as a Risk Factor for Acute and Chronic Pancreatitis: A Systematic Review and a Series of Meta-analyses. AB - BACKGROUND: Pancreatitis is a highly prevalent medical condition associated with a spectrum of endocrine and exocrine pancreatic insufficiencies. While high alcohol consumption is an established risk factor for pancreatitis, its relationship with specific types of pancreatitis and a potential threshold have not been systematically examined. METHODS: We conducted a systematic literature search for studies on the association between alcohol consumption and pancreatitis based on PRISMA guidelines. Non-linear and linear random-effect dose response meta-analyses using restricted cubic spline meta-regressions and categorical meta-analyses in relation to abstainers were conducted. FINDINGS: Seven studies with 157,026 participants and 3618 cases of pancreatitis were included into analyses. The dose-response relationship between average volume of alcohol consumption and risk of pancreatitis was monotonic with no evidence of non-linearity for chronic pancreatitis (CP) for both sexes (p = 0.091) and acute pancreatitis (AP) in men (p = 0.396); it was non-linear for AP in women (p = 0.008). Compared to abstention, there was a significant decrease in risk (RR = 0.76, 95%CI: 0.60-0.97) of AP in women below the threshold of 40 g/day. No such association was found in men (RR = 1.1, 95%CI: 0.69-1.74). The RR for CP at 100 g/day was 6.29 (95%CI: 3.04-13.02). INTERPRETATION: The dose-response relationships between alcohol consumption and risk of pancreatitis were monotonic for CP and AP in men, and non-linear for AP in women. Alcohol consumption below 40 g/day was associated with reduced risk of AP in women. Alcohol consumption beyond this level was increasingly detrimental for any type of pancreatitis. FUNDING: The work was financially supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (R21AA023521) to the last author. PMID- 26844278 TI - A Phase I Safety, Pharmacokinetic, and Pharmacodynamic Presurgical Trial of Vitamin E delta-tocotrienol in Patients with Pancreatic Ductal Neoplasia. AB - BACKGROUND: Vitamin E delta-tocotrienol (VEDT), a natural vitamin E from plants, has shown anti-neoplastic and chemoprevention activity in preclinical models of pancreatic cancer. Here, we investigated VEDT in patients with pancreatic ductal neoplasia in a window-of-opportunity preoperative clinical trial to assess its safety, tolerability, pharmacokinetics, and apoptotic activity. METHODS: Patients received oral VEDT at escalating doses (from 200 to 3200 mg) daily for 13 days before surgery and one dose on the day of surgery. Dose escalation followed a three-plus-three trial design. Our primary endpoints were safety, VEDT pharmacokinetics, and monitoring of VEDT-induced neoplastic cell apoptosis (ClinicalTrials.gov number NCT00985777). FINDINGS: In 25 treated patients, no dose-limiting toxicity was encountered; thus no maximum-tolerated dose was reached. One patient had a drug-related adverse event (diarrhea) at a 3200-mg daily dose level. The effective half-life of VEDT was ~ 4 h. VEDT concentrations in plasma and exposure profiles were quite variable but reached levels that are bioactive in preclinical models. Biological activity, defined as significant induction of apoptosis in neoplastic cells as measured by increased cleaved caspase-3 levels, was seen in the majority of patients at the 400-mg to 1600-mg daily dose levels. INTERPRETATION: VEDT from 200 to 1600 mg daily taken orally for 2 weeks before pancreatic surgery was well tolerated, reached bioactive levels in blood, and significantly induced apoptosis in the neoplastic cells of patients with pancreatic ductal neoplasia. These promising results warrant further clinical investigation of VEDT for chemoprevention and/or therapy of pancreatic cancer. PMID- 26844280 TI - Exercise Increases 24-h Fat Oxidation Only When It Is Performed Before Breakfast. AB - BACKGROUND: As part of the growing lifestyle diversity in modern society, there is wide variation in the time of day individuals choose to exercise. Recent surveys in the US and Japan have reported that on weekdays, more people exercise in the evening, with fewer individuals exercising in the morning or afternoon. Exercise performed in the post-prandial state has little effect on accumulated fat oxidation over 24 h (24-h fat oxidation) when energy intake is matched to energy expenditure (energy-balanced condition). The present study explored the possibility that exercise increases 24-h fat oxidation only when performed in a post-absorptive state, i.e. before breakfast. METHODS: Indirect calorimetry using a metabolic chamber was performed in 10 young, non-obese men over 24 h. Subjects remained sedentary (control) or performed 60-min exercise before breakfast (morning), after lunch (afternoon), or after dinner (evening) at 50% of VO2max. All trials were designed to be energy balanced over 24 h. Time course of energy and substrate balance relative to the start of calorimetry were estimated from the differences between input (meal consumption) and output (oxidation). FINDINGS: Fat oxidation over 24 h was increased only when exercise was performed before breakfast (control, 456 +/- 61; morning, 717 +/- 64; afternoon, 446 +/- 57; and evening, 432 +/- 44 kcal/day). Fat oxidation over 24 h was negatively correlated with the magnitude of the transient deficit in energy and carbohydrate. INTERPRETATION: Under energy-balanced conditions, 24-h fat oxidation was increased by exercise only when performed before breakfast. Transient carbohydrate deficits, i.e., glycogen depletion, observed after morning exercise may have contributed to increased 24-h fat oxidation. PMID- 26844281 TI - Genetically Low Antioxidant Protection and Risk of Cardiovascular Disease and Heart Failure in Diabetic Subjects. AB - BACKGROUND: Hyperglycemia-induced oxidative stress is one mechanism believed to underlie diabetic vascular disease. We tested the hypothesis that diabetic subjects heterozygous for extracellular superoxide dismutase (SOD3) R213G, which entails lower antioxidant capacity in tissues, have increased risk of cardiovascular disease and heart failure. METHODS: We used the prospective Copenhagen General Population Study and Copenhagen City Heart Study and genotyped 95,871 individuals for the rs1799895 R213G variation in the SOD3 gene, of which 4498 had diabetes. We used national hospitalization and death registers to assess cardiovascular disease and heart failure. FINDINGS: Out of 95,871 individuals, we identified 93,521 R213G non-carriers (213RR, 97.5%), 2336 heterozygotes (213RG, 2.4%) and 14 homozygotes (213GG, 0.01%). In diabetic subjects, the hazard ratio for cardiovascular disease in R213G heterozygotes compared to non-carriers was 2.32 (95% CI 1.44-3.75), with a corresponding hazard ratio in non-diabetic subjects of 0.97 (0.80-1.19) (p for interaction 0.002). For heart failure, the hazard ratios in R213G heterozygotes compared to non-carriers were 2.19 (1.28 3.76) in diabetic and 0.68 (0.49-0.92) in non-diabetic subjects (p for interaction < 0.001). INTERPRETATION: Risk of cardiovascular disease and heart failure was higher in R213G heterozygotes versus non-carriers in diabetic subjects, but not in non-diabetic subjects. PMID- 26844282 TI - A High Level of Intestinal Alkaline Phosphatase Is Protective Against Type 2 Diabetes Mellitus Irrespective of Obesity. AB - Mice deficient in intestinal alkaline phosphatase (IAP) develop type 2 diabetes mellitus (T2DM). We hypothesized that a high level of IAP might be protective against T2DM in humans. We determined IAP levels in the stools of 202 diabetic patients and 445 healthy non-diabetic control people. We found that compared to controls, T2DM patients have approx. 50% less IAP (mean +/- SEM: 67.4 +/- 3.2 vs 35.3 +/- 2.5 U/g stool, respectively; p < 0.000001) indicating a protective role of IAP against T2DM. Multiple logistic regression analyses showed an independent association between the IAP level and diabetes status. With each 25 U/g decrease in stool IAP, there is a 35% increased risk of diabetes. The study revealed that obese people with high IAP (approx. 65 U/g stool) do not develop T2DM. Approx. 65% of the healthy population have < 65.0 U/g stool IAP, and predictably, these people might have 'the incipient metabolic syndrome', including 'incipient diabetes', and might develop T2DM and other metabolic disorders in the near future. In conclusion, high IAP levels appear to be protective against diabetes irrespective of obesity, and a 'temporal IAP profile' might be a valuable tool for predicting 'the incipient metabolic syndrome', including 'incipient diabetes'. PMID- 26844283 TI - Modulation of Autoimmune T-Cell Memory by Stem Cell Educator Therapy: Phase 1/2 Clinical Trial. AB - BACKGROUND: Type 1 diabetes (T1D) is a T cell-mediated autoimmune disease that causes a deficit of pancreatic islet beta cells. The complexities of overcoming autoimmunity in T1D have contributed to the challenges the research community faces when devising successful treatments with conventional immune therapies. Overcoming autoimmune T cell memory represents one of the key hurdles. METHODS: In this open-label, phase 1/phase 2 study, Caucasian T1D patients (N = 15) received two treatments with the Stem Cell Educator (SCE) therapy, an approach that uses human multipotent cord blood-derived multipotent stem cells (CB-SCs). SCE therapy involves a closed-loop system that briefly treats the patient's lymphocytes with CB-SCs in vitro and returns the "educated" lymphocytes (but not the CB-SCs) into the patient's blood circulation. This study is registered with ClinicalTrials.gov, NCT01350219. FINDINGS: Clinical data demonstrated that SCE therapy was well tolerated in all subjects. The percentage of naive CD4(+) T cells was significantly increased at 26 weeks and maintained through the final follow-up at 56 weeks. The percentage of CD4(+) central memory T cells (TCM) was markedly and constantly increased at 18 weeks. Both CD4(+) effector memory T cells (TEM) and CD8(+) TEM cells were considerably decreased at 18 weeks and 26 weeks respectively. Additional clinical data demonstrated the modulation of C-C chemokine receptor 7 (CCR7) expressions on naive T, TCM, and TEM cells. Following two treatments with SCE therapy, islet beta-cell function was improved and maintained in individuals with residual beta-cell function, but not in those without residual beta-cell function. INTERPRETATION: Current clinical data demonstrated the safety and efficacy of SCE therapy in immune modulation. SCE therapy provides lasting reversal of autoimmune memory that could improve islet beta-cell function in Caucasian subjects. FUNDING: Obra Social "La Caixa", Instituto de Salud Carlos III, Red de Investigacion Renal, European Union FEDER Funds, Principado de Asturias, FICYT, and Hackensack University Medical Center Foundation. PMID- 26844284 TI - Collagen Specific T-Cell Repertoire and HLA-DR Alleles: Biomarkers of Active Refractory Rheumatoid Arthritis. AB - Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and associates with HLA-DRB1*04. The Collagen IIp261-273-specific T cell repertoire in the peripheral blood of DR4 + patients at the onset of the disease shows a restricted TCR-beta chain usage among which the most frequent is TRBV25. To define whether this group of DR4-restricted collagen-specific shared T cell could represent markers of active-severe disease and response to therapy, 90 subjects affected by early-RA were enrolled in the study; peripheral blood mononuclear cells were cultured with or without the human collagen II peptide p261-273 and were examined by immunoscope analysis for the usage of the previously identified shared TCR-beta chains. We report that the presence of T cells carrying rearrangement TRBV25 associated with HLA-DR haplotype and disease activity. HLA DRB1* haplotypes 04-04, 04-01 and 04-11 were significantly associated with usage of TRBV25, higher disease activity at the onset of disease and poor response to DMARDs. Finally, the HLA-DRB1* haplotype appeared complementary with current serologic tools to predict good and poor responders in a treat to target strategy. The data reported here offer clues to predict the course of the disease and to foresee personalized treatments in RA patients. PMID- 26844285 TI - Lansoprazole Upregulates Polyubiquitination of the TNF Receptor-Associated Factor 6 and Facilitates Runx2-mediated Osteoblastogenesis. AB - The transcription factor, runt-related transcription factor 2 (Runx2), plays a pivotal role in the differentiation of the mesenchymal stem cells to the osteochondroblast lineages. We found by the drug repositioning strategy that a proton pump inhibitor, lansoprazole, enhances nuclear accumulation of Runx2 and induces osteoblastogenesis of human mesenchymal stromal cells. Systemic administration of lansoprazole to a rat femoral fracture model increased osteoblastogenesis. Dissection of signaling pathways revealed that lansoprazole activates a noncanonical bone morphogenic protein (BMP)-transforming growth factor-beta (TGF-beta) activated kinase-1 (TAK1)-p38 mitogen-activated protein kinase (MAPK) pathway. We found by in cellulo ubiquitination studies that lansoprazole enhances polyubiquitination of the TNF receptor-associated factor 6 (TRAF6) and by in vitro ubiquitination studies that the enhanced polyubiquitination of TRAF6 is attributed to the blocking of a deubiquitination enzyme, cylindromatosis (CYLD). Structural modeling and site-directed mutagenesis of CYLD demonstrated that lansoprazole tightly fits in a pocket of CYLD where the C-terminal tail of ubiquitin lies. Lansoprazole is a potential therapeutic agent for enhancing osteoblastic differentiation. PMID- 26844286 TI - Are Clade Specific HIV Vaccines a Necessity? An Analysis Based on Mathematical Models. AB - As HIV-1 envelope immune responses are critical to vaccine related protection, most candidate HIV vaccines entering efficacy trials are based upon a clade specific design. This need for clade specific vaccine prototypes markedly reduces the implementation of potentially effective HIV vaccines. We utilized a mathematical model to determine the effectiveness of immediate roll-out of a non clade matched vaccine with reduced efficacy compared to constructing clade specific vaccines, which would take considerable time to manufacture and test in safety and efficacy trials. We simulated the HIV epidemic in San Francisco (SF) and South Africa (SA) and projected effectiveness of three vaccination strategies: i) immediate intervention with a 20-40% vaccine efficacy (VE) non matched vaccine, ii) delayed intervention by developing a 50% VE clade-specific vaccine, and iii) immediate intervention with a non-matched vaccine replaced by a clade-specific vaccine when developed. Immediate vaccination with a non-clade matched vaccine, even with reduced efficacy, would prevent thousands of new infections in SF and millions in SA over 30 years. Vaccination with 50% VE delayed for five years needs six and 12 years in SA to break-even with immediate 20 and 30% VE vaccination, respectively, while not able to surpass the impact of immediate 40% VE vaccination over 30 years. Replacing a 30% VE with a 50% VE vaccine after 5 years reduces the HIV acquisition by 5% compared to delayed vaccination. The immediate use of an HIV vaccine with reduced VE in high risk communities appears desirable over a short time line but higher VE should be the pursued to achieve strong long-term impact. Our analysis illustrates the importance of developing surrogate markers (correlates of protection) to allow bridging types of immunogenicity studies to support more rapid assessment of clade specific vaccines. PMID- 26844287 TI - Analysis of B Cell Repertoire Dynamics Following Hepatitis B Vaccination in Humans, and Enrichment of Vaccine-specific Antibody Sequences. AB - Generating a diverse B cell immunoglobulin repertoire is essential for protection against infection. The repertoire in humans can now be comprehensively measured by high-throughput sequencing. Using hepatitis B vaccination as a model, we determined how the total immunoglobulin sequence repertoire changes following antigen exposure in humans, and compared this to sequences from vaccine-specific sorted cells. Clonal sequence expansions were seen 7 days after vaccination, which correlated with vaccine-specific plasma cell numbers. These expansions caused an increase in mutation, and a decrease in diversity and complementarity determining region 3 sequence length in the repertoire. We also saw an increase in sequence convergence between participants 14 and 21 days after vaccination, coinciding with an increase of vaccine-specific memory cells. These features allowed development of a model for in silico enrichment of vaccine-specific sequences from the total repertoire. Identifying antigen-specific sequences from total repertoire data could aid our understanding B cell driven immunity, and be used for disease diagnostics and vaccine evaluation. PMID- 26844288 TI - Hepatitis E Virus Superinfection and Clinical Progression in Hepatitis B Patients. AB - Hepatitis E virus (HEV) infection may cause acute hepatitis and lead to hepatic failure in developing and developed countries. We studied HEV seroprevalences in patients with hepatitis B virus (HBV) infection to understand the consequences of HEV superinfection in a Vietnamese population. This cross-sectional study was conducted from 2012 to 2013 and included 1318 Vietnamese patients with HBV related liver diseases and 340 healthy controls. The case group included patients with acute (n = 26) and chronic hepatitis B (n = 744), liver cirrhosis (n = 160), hepatocellular carcinoma (n = 166) and patients with both liver cirrhosis and hepatocellular carcinoma (n = 222). Anti-HEV IgG and IgM antibodies were assessed in patients and controls by ELISA. HEV-RNA was identified by PCR assays and sequencing. Seroprevalences of anti-HEV IgG among hepatitis B patients and controls were 45% and 31%, respectively (adjusted P = 0.034). Anti-HEV IgM seroprevalences were 11.6% and 4.7% in patients and controls, respectively (adjusted P = 0.005). Seroprevalences were higher among the elder individuals. When stratifying for patient groups, those with liver cirrhosis had the highest anti-HEV IgG (52%) and anti-HEV IgM (19%) seroprevalences. Hepatitis B patients with current HEV infection had abnormal liver function tests compared to patients with past or without HEV infection. One HEV isolate was retrieved from a patient with both liver cirrhosis and hepatocellular carcinoma and identified as HEV genotype 3. This study indicates high prevalences of HEV infection in Vietnamese HBV patients and among healthy individuals and shows that HEV superinfection may influence the outcome and progression of HBV-related liver disease. PMID- 26844290 TI - Absence of a Socioeconomic Gradient in Older Adults' Survival with Multiple Chronic Conditions. AB - BACKGROUND: Individuals of low socioeconomic status experience a disproportionate burden of chronic conditions; however it is unclear whether chronic condition burden affects survival differently across socioeconomic strata. METHODS: This retrospective cohort study used health administrative data from all residents of Ontario, Canada aged 65 to 105 with at least one of 16 chronic conditions on April 1, 2009 (n = 1,518,939). Chronic condition burden and unadjusted mortality were compared across neighborhood income quintiles. Multivariable Cox proportional hazards models were used to examine the effect of number of chronic conditions on two-year survival across income quintiles. FINDINGS: Prevalence of five or more chronic conditions was significantly higher among older adults in the poorest neighborhoods (18.2%) than the wealthiest (14.3%) (Standardized difference > 0.1). There was also a socioeconomic gradient in unadjusted mortality over two years: 10.1% of people in the poorest neighborhoods died compared with 7.6% of people in the wealthiest neighborhoods. In adjusted analyses, having more chronic conditions was associated with a statistically significant increase in hazard of death over two years, however the magnitude of this effect was comparable across income quintiles. Individuals in the poorest neighborhoods with four chronic conditions had 2.07 times higher hazard of death (95% CI: 1.97-2.19) than those with one chronic condition, but this was comparable to the hazard associated with four chronic conditions in the wealthiest neighborhoods (HR: 2.29, 95% CI: 2.16-2.43). INTERPRETATION: Among older adults with universal access to health care, the deleterious effect of increasing chronic condition burden on two-year hazard of death was consistent across neighborhood income quintiles once baseline differences in condition burden were accounted for. This may be partly attributable to equal access to, and utilization of, health care. Alternate explanations for these findings, including study limitations, are also discussed. PMID- 26844289 TI - Prospective Testing and Redesign of a Temporal Biomarker Based Risk Model for Patients With Septic Shock: Implications for Septic Shock Biology. AB - The temporal version of the pediatric sepsis biomarker risk model (tPERSEVERE) estimates the risk of a complicated course in children with septic shock based on biomarker changes from days 1 to 3 of septic shock. We validated tPERSEVERE performance in a prospective cohort, with an a priori plan to redesign tPERSEVERE if it did not perform well. Biomarkers were measured in the validation cohort (n = 168) and study subjects were classified according to tPERSEVERE. To redesign tPERSEVERE, the validation cohort and the original derivation cohort (n = 299) were combined and randomly allocated to training (n = 374) and test (n = 93) sets. tPERSEVERE was redesigned using the training set and CART methodology. tPERSEVERE performed poorly in the validation cohort, with an area under the curve (AUC) of 0.67 (95% CI: 0.58-0.75). Failure analysis revealed potential confounders related to clinical characteristics. The redesigned tPERSEVERE model had an AUC of 0.83 (0.79-0.87) and a sensitivity of 93% (68-97) for estimating the risk of a complicated course. Similar performance was seen in the test set. The classification tree segregated patients into two broad endotypes of septic shock characterized by either excessive inflammation or immune suppression. PMID- 26844292 TI - Associations between Inadequate Parenting Practices and Behavioral Problems in Children and Adolescents with Attention Deficit Hyperactivity Disorder. AB - Children and adolescents with ADHD present behaviors such as impulsiveness, inattention, and difficulties with personal organization that represent an overload for parents. Moreover, it also increases their level of stress and leads them to resort to inadequate educational strategies. The present study verifies associations between inadequate parenting practices and behavioral profiles of children and adolescents with ADHD. The sample was composed of 22 children with ADHD (age range 6-16 years) and their mothers. Spearman correlation analyses were made with the scores of Parenting Style Inventory (PSI) and Child Behavior Checklist for ages 6-18 (CBCL/6-18). Results indicate statistically significant associations between behavioral problems and the use of punishment practices and negligence. When assessing a child with ADHD, it is important to verify the predominant types of parenting practices that can influence both immediate interventions and the prognosis of the disorder. PMID- 26844291 TI - Economics and Outcome After Hematopoietic Stem Cell Transplantation: A Retrospective Cohort Study. AB - Hematopoietic stem cell transplantation (HSCT) is a lifesaving expensive medical procedure. Hence, more transplants are performed in more affluent countries. The impact of economic factors on patient outcome is less defined. We analyzed retrospectively a defined cohort of 102,549 patients treated with an allogeneic (N = 37,542; 37%) or autologous (N = 65,007; 63%) HSCT. They were transplanted by one of 404 HSCT centers in 25 European countries between 1999 and 2006. We searched for associations between center-specific microeconomic or country specific macroeconomic factors and outcome. Center patient-volume and center program-duration were significantly and systematically associated with improved survival after allogeneic HSCT (HR 0.87; 0.84-0.91 per 10 patients; p < 0.0001; HR 0.90;0.85-0.90 per 10 years; p < 0.001) and autologous HSCT (HR 0.91;0.87-0.96 per 10 patients; p < 0.001; HR 0.93;0.87-0.99 per 10 years; p = 0.02). The product of Health Care Expenditures by Gross National Income/capita was significantly associated in multivariate analysis with all endpoints (R(2) = 18%; for relapse free survival) after allogeneic HSCT. Data indicate that country- and center-specific economic factors are associated with distinct, significant, systematic, and clinically relevant effects on survival after HSCT. They impact on center expertise in long-term disease and complication management. It is likely that these findings apply to other forms of complex treatments. PMID- 26844293 TI - Environmental changes bridge evolutionary valleys. AB - In the basic fitness landscape metaphor for molecular evolution, evolutionary pathways are presumed to follow uphill steps of increasing fitness. How evolution can cross fitness valleys is an open question. One possibility is that environmental changes alter the fitness landscape such that low-fitness sequences reside on a hill in alternate environments. We experimentally test this hypothesis on the antibiotic resistance gene TEM-15 beta-lactamase by comparing four evolutionary strategies shaped by environmental changes. The strategy that included initial steps of selecting for low antibiotic resistance (negative selection) produced superior alleles compared with the other three strategies. We comprehensively examined possible evolutionary pathways leading to one such high fitness allele and found that an initially deleterious mutation is key to the allele's evolutionary history. This mutation is an initial gateway to an otherwise relatively inaccessible area of sequence space and participates in higher-order, positive epistasis with a number of neutral to slightly beneficial mutations. The ability of negative selection and environmental changes to provide access to novel fitness peaks has important implications for natural evolutionary mechanisms and applied directed evolution. PMID- 26844294 TI - Costs of migratory decisions: A comparison across eight white stork populations. AB - Annual migratory movements can range from a few tens to thousands of kilometers, creating unique energetic requirements for each specific species and journey. Even within the same species, migration costs can vary largely because of flexible, opportunistic life history strategies. We uncover the large extent of variation in the lifetime migratory decisions of young white storks originating from eight populations. Not only did juvenile storks differ in their geographically distinct wintering locations, their diverse migration patterns also affected the amount of energy individuals invested for locomotion during the first months of their life. Overwintering in areas with higher human population reduced the stork's overall energy expenditure because of shorter daily foraging trips, closer wintering grounds, or a complete suppression of migration. Because migrants can change ecological processes in several distinct communities simultaneously, understanding their life history decisions helps not only to protect migratory species but also to conserve stable ecosystems. PMID- 26844295 TI - Seasonal reproductive endothermy in tegu lizards. AB - With some notable exceptions, small ectothermic vertebrates are incapable of endogenously sustaining a body temperature substantially above ambient temperature. This view was challenged by our observations of nighttime body temperatures sustained well above ambient (up to 10 degrees C) during the reproductive season in tegu lizards (~2 kg). This led us to hypothesize that tegus have an enhanced capacity to augment heat production and heat conservation. Increased metabolic rates and decreased thermal conductance are the same mechanisms involved in body temperature regulation in those vertebrates traditionally acknowledged as "true endotherms": the birds and mammals. The appreciation that a modern ectotherm the size of the earliest mammals can sustain an elevated body temperature through metabolic rates approaching that of endotherms enlightens the debate over endothermy origins, providing support for the parental care model of endothermy, but not for the assimilation capacity model of endothermy. It also indicates that, contrary to prevailing notions, ectotherms can engage in facultative endothermy, providing a physiological analog in the evolutionary transition to true endothermy. PMID- 26844297 TI - An iron-iron hydrogenase mimic with appended electron reservoir for efficient proton reduction in aqueous media. AB - The transition from a fossil-based economy to a hydrogen-based economy requires cheap and abundant, yet stable and efficient, hydrogen production catalysts. Nature shows the potential of iron-based catalysts such as the iron-iron hydrogenase (H2ase) enzyme, which catalyzes hydrogen evolution at rates similar to platinum with low overpotential. However, existing synthetic H2ase mimics generally suffer from low efficiency and oxygen sensitivity and generally operate in organic solvents. We report on a synthetic H2ase mimic that contains a redox active phosphole ligand as an electron reservoir, a feature that is also crucial for the working of the natural enzyme. Using a combination of (spectro)electrochemistry and time-resolved infrared spectroscopy, we elucidate the unique redox behavior of the catalyst. We find that the electron reservoir actively partakes in the reduction of protons and that its electron-rich redox states are stabilized through ligand protonation. In dilute sulfuric acid, the catalyst has a turnover frequency of 7.0 * 10(4) s(-1) at an overpotential of 0.66 V. This catalyst is tolerant to the presence of oxygen, thereby paving the way for a new generation of synthetic H2ase mimics that combine the benefits of the enzyme with synthetic versatility and improved stability. PMID- 26844296 TI - A novel persulfide detection method reveals protein persulfide- and polysulfide reducing functions of thioredoxin and glutathione systems. AB - Hydrogen sulfide signaling involves persulfide formation at specific protein Cys residues. However, overcoming current methodological challenges in persulfide detection and elucidation of Cys regeneration mechanisms from persulfides are prerequisites for constructing a bona fide signaling model. We here establish a novel, highly specific protein persulfide detection protocol, ProPerDP, with which we quantify 1.52 +/- 0.6 and 11.6 +/- 6.9 MUg/mg protein steady-state protein persulfide concentrations in human embryonic kidney 293 (HEK293) cells and mouse liver, respectively. Upon treatment with polysulfides, HEK293 and A549 cells exhibited increased protein persulfidation. Deletion of the sulfide producing cystathionine-gamma-lyase or cystathionine-beta-synthase enzymes in yeast diminished protein persulfide levels, thereby corroborating their involvement in protein persulfidation processes. We here establish that thioredoxin (Trx) and glutathione (GSH) systems can independently catalyze reductions of inorganic polysulfides and protein persulfides. Increased endogenous persulfide levels and protein persulfidation following polysulfide treatment in thioredoxin reductase-1 (TrxR1) or thioredoxin-related protein of 14 kDa (TRP14) knockdown HEK293 cells indicated that these enzymes constitute a potent regeneration system of Cys residues from persulfides in a cellular context. Furthermore, TrxR1-deficient cells were less viable upon treatment with toxic amounts of polysulfides compared to control cells. Emphasizing the dominant role of cytosolic disulfide reduction systems in maintaining sulfane sulfur homeostasis in vivo, protein persulfide levels were markedly elevated in mouse livers where hepatocytes lack both TrxR1 and glutathione reductase (TR/GR-null). The different persulfide patterns observed in wild-type, GR-null, and TR/GR-null livers suggest distinct roles for the Trx and GSH systems in regulating subsets of protein persulfides and thereby fine-tuning sulfide signaling pathways. PMID- 26844298 TI - Environmentally-friendly aqueous Li (or Na)-ion battery with fast electrode kinetics and super-long life. AB - Current rechargeable batteries generally display limited cycle life and slow electrode kinetics and contain environmentally unfriendly components. Furthermore, their operation depends on the redox reactions of metal elements. We present an original battery system that depends on the redox of I(-)/I3 (-) couple in liquid cathode and the reversible enolization in polyimide anode, accompanied by Li(+) (or Na(+)) diffusion between cathode and anode through a Li(+)/Na(+) exchange polymer membrane. There are no metal element-based redox reactions in this battery, and Li(+) (or Na(+)) is only used for charge transfer. Moreover, the components (electrolyte/electrode) of this system are environment friendly. Both electrodes are demonstrated to have very fast kinetics, which gives the battery a supercapacitor-like high power. It can even be cycled 50,000 times when operated within the electrochemical window of 0 to 1.6 V. Such a system might shed light on the design of high-safety and low-cost batteries for grid-scale energy storage. PMID- 26844299 TI - Tunable light emission by exciplex state formation between hybrid halide perovskite and core/shell quantum dots: Implications in advanced LEDs and photovoltaics. AB - We report the first observation of exciplex state electroluminescence due to carrier injection between the hybrid lead halide perovskite (MAPbI3-xClx) and quantum dots (core/shell PbS/CdS). Single layers of perovskite (PS) and quantum dots (QDs) have been produced by solution processing methods, and their photoluminescent properties are compared to those of bilayer samples in both PS/QD and QD/PS configurations. Exciplex emission at lower energies than the band gap of both PS and QD has been detected. The exciplex emission wavelength of this mixed system can be simply tuned by controlling the QD size. Light-emitting diodes (LEDs) have been fabricated using those configurations, which provide light emission with considerably low turn-on potential. The "color" of the LED can also be tuned by controlling the applied bias. The presence of the exciplex state PS and QDs opens up a broad range of possibilities with important implications not only in tunable LEDs but also in the preparation of intermediate band gap photovoltaic devices with the potentiality of surpassing the Shockley Queisser limit. PMID- 26844300 TI - Metainference: A Bayesian inference method for heterogeneous systems. AB - Modeling a complex system is almost invariably a challenging task. The incorporation of experimental observations can be used to improve the quality of a model and thus to obtain better predictions about the behavior of the corresponding system. This approach, however, is affected by a variety of different errors, especially when a system simultaneously populates an ensemble of different states and experimental data are measured as averages over such states. To address this problem, we present a Bayesian inference method, called "metainference," that is able to deal with errors in experimental measurements and with experimental measurements averaged over multiple states. To achieve this goal, metainference models a finite sample of the distribution of models using a replica approach, in the spirit of the replica-averaging modeling based on the maximum entropy principle. To illustrate the method, we present its application to a heterogeneous model system and to the determination of an ensemble of structures corresponding to the thermal fluctuations of a protein molecule. Metainference thus provides an approach to modeling complex systems with heterogeneous components and interconverting between different states by taking into account all possible sources of errors. PMID- 26844302 TI - Feasibility of Imaging Tissue Electrical Conductivity by Switching Field Gradients with MRI. AB - Tissue conductivity is a biophysical marker of tissue structure and physiology. Present methods of measuring tissue conductivity are limited. Electrical impedance tomography, and magnetic resonance electrical impedance tomography rely on passing external current through the object being imaged, which prevents its use in most human imaging. Recently, the RF field used for MR excitation has been used to non-invasively measure tissue conductivity. This technique is promising, but conductivity at higher frequencies is less sensitive to tissue structure. Measuring tissue conductivity non-invasively at low frequencies remains elusive. It has been proposed that eddy currents generated during the rise and decay of gradient pulses could act as a current source to map low-frequency conductivity. This work centers on a gradient echo pulse sequence that uses large gradients prior to excitation to create eddy currents. The electric and magnetic fields during a gradient pulse are simulated by a finite-difference time-domain simulation. The sequence is also tested with a phantom and an animal MRI scanner equipped with gradients of high gradient strengths and slew rate. The simulation demonstrates that eddy currents in materials with conductivity similar to biological tissue decay with a half-life on the order of nanoseconds and any eddy currents generated prior to excitation decay completely before influencing the RF signal. Gradient-induced eddy currents can influence phase accumulation after excitation but the effect is too small to image. The animal scanner images show no measurable phase accumulation. Measuring low-frequency conductivity by gradient-induced eddy currents is presently unfeasible. PMID- 26844301 TI - Quantitative Susceptibility Mapping: Contrast Mechanisms and Clinical Applications. AB - Quantitative susceptibility mapping (QSM) is a recently developed MRI technique for quantifying the spatial distribution of magnetic susceptibility within biological tissues. It first uses the frequency shift in the MRI signal to map the magnetic field profile within the tissue. The resulting field map is then used to determine the spatial distribution of the underlying magnetic susceptibility by solving an inverse problem. The solution is achieved by deconvolving the field map with a dipole field, under the assumption that the magnetic field is a result of the superposition of the dipole fields generated by all voxels and that each voxel has its unique magnetic susceptibility. QSM provides improved contrast to noise ratio for certain tissues and structures compared to its magnitude counterpart. More importantly, magnetic susceptibility is a direct reflection of the molecular composition and cellular architecture of the tissue. Consequently, by quantifying magnetic susceptibility, QSM is becoming a quantitative imaging approach for characterizing normal and pathological tissue properties. This article reviews the mechanism generating susceptibility contrast within tissues and some associated applications. PMID- 26844303 TI - The impact of beat-to-beat variability in optimising the acute hemodynamic response in cardiac resynchronisation therapy. AB - BACKGROUND: Acute indicators of response to cardiac resynchronisation therapy (CRT) are critical for developing lead optimisation algorithms and evaluating novel multi-polar, multi-lead and endocardial pacing protocols. Accounting for beat-to-beat variability in measures of acute haemodynamic response (AHR) may help clinicians understand the link between acute measurements of cardiac function and long term clinical outcome. METHODS AND RESULTS: A retrospective study of invasive pressure tracings from 38 patients receiving an acute pacing and electrophysiological study was performed. 602 pacing protocols for left ventricle (LV) (n = 38), atria-ventricle (AV) (n = 9), ventricle-ventricle (VV) (n = 12) and endocardial (ENDO) (n = 8) optimisation were performed. AHR was measured as the maximal rate of LV pressure development (dP/dtMx) for each beat. The range of the 95% confidence interval (CI) of mean AHR was ~ 7% across all optimisation protocols compared with the reported CRT response cut off value of 10%. A single clear optimal protocol was identifiable in 61%, 22%, 25% and 50% for LV, AV, VV and ENDO optimisation cases, respectively. A level of service (LOS) optimisation that aimed to maximise the expected AHR 5th percentile, minimising variability and maximising AHR, led to distinct optimal protocols from conventional mean AHR optimisation in 34%, 78%, 67% and 12.5% of LV, AV, VV and ENDO optimisation cases, respectively. CONCLUSION: The beat-to-beat variation in AHR is significant in the context of CRT cut off values. A LOS optimisation offers a novel index to identify the optimal pacing site that accounts for both the mean and variation of the baseline measurement and pacing protocol. PMID- 26844305 TI - Message from the Editor-in-Chief. PMID- 26844304 TI - Surpassing Humans and Computers with JellyBean: Crowd-Vision-Hybrid Counting Algorithms. AB - Counting objects is a fundamental image processisng primitive, and has many scientific, health, surveillance, security, and military applications. Existing supervised computer vision techniques typically require large quantities of labeled training data, and even with that, fail to return accurate results in all but the most stylized settings. Using vanilla crowd-sourcing, on the other hand, can lead to significant errors, especially on images with many objects. In this paper, we present our JellyBean suite of algorithms, that combines the best of crowds and computer vision to count objects in images, and uses judicious decomposition of images to greatly improve accuracy at low cost. Our algorithms have several desirable properties: (i) they are theoretically optimal or near optimal, in that they ask as few questions as possible to humans (under certain intuitively reasonable assumptions that we justify in our paper experimentally); (ii) they operate under stand-alone or hybrid modes, in that they can either work independent of computer vision algorithms, or work in concert with them, depending on whether the computer vision techniques are available or useful for the given setting; (iii) they perform very well in practice, returning accurate counts on images that no individual worker or computer vision algorithm can count correctly, while not incurring a high cost. PMID- 26844306 TI - Message from the Paper Chairs and Guest Editors. PMID- 26844307 TI - How to learn most about your patients. PMID- 26844308 TI - An integrating perspective. PMID- 26844361 TI - Transformations of Conjugated Enynones in the Superacid CF3SO3H. Synthesis of Butadienyl Triflates, Indanones, and Indenes. AB - Conjugated 1,5-diarylpent-2-en-4-yn-1-ones add the superacid CF3SO3H to the acetylenic bond with formation of the corresponding butadienyl triflates. Under superacidic reaction conditions, these triflates are transformed into indanone or indene derivatives depending on which substituents on the aromatic ring are conjugated with the butadiene fragment. In a less acidic system (10% vol pyridine in CF3SO3H) only the formation of butadienyl triflates takes place. Cationic reaction intermediates were studied by means of NMR and DFT calculations. PMID- 26844309 TI - Reply to Nellen et al's comment on the classification of clinical/genetic variants of Mal de Meleda. PMID- 26844362 TI - Syntheses, Structures, and Nonlinear Optical Properties of Two Sulfides Na2In2MS6 (M = Si, Ge). AB - The first two new Na-containing sulfides Na2In2MS6 (M = Si (1), Ge (2)) in the Na2Q-B2Q3-CQ2 (B = Ga, In; C = Si, Ge, Sn; Q = S, Se) system were prepared for the first time through conventional high-temperature solid-state reaction. They are isostructural with space group Cc (No. 9) in monoclinic phases and feature three-dimensional frameworks built by the (infinity)1[In2MS6]2- (M = Si, Ge) chains through corner-sharing InS4 tetrahedra and MS4 (M = Si, Ge) tetrahedra, with Na+ cation located in the cavities. They display moderate second harmonic generation (SHG) conversion efficiencies compared with commercial AgGaS2, with phase-matching behavior at 1800 nm and laser-induced damage thresholds 6.9 and 4.0 times higher than that of AgGaS2, respectively. Therefore, the output SHG intensities of 1 and 2 will be ~4.3 and 4.0 times larger than that of AgGaS2, when the intensity of incident laser increased to close the damage energy of 1 and 2, indicating their potential for high-power nonlinear optical application. PMID- 26844364 TI - Liver Fibrosis Staging with MR Elastography: Comparison of Diagnostic Performance between Patients with Chronic Hepatitis B and Those with Other Etiologic Causes. AB - Purpose To evaluate the diagnostic performance of magnetic resonance (MR) elastography in staging liver fibrosis in patients with chronic hepatitis B (CHB) and other etiologic causes. Materials and Methods This retrospective study was institutional review board-approved and the requirement for informed consent was waived. Before surgery, MR elastographic imaging was performed in 352 patients with chronic liver diseases (281 patients with CHB, 71 patients without CHB) and hepatocellular carcinomas and 64 living liver donor candidates. Liver stiffness (LS) values were measured on quantitative shear-stiffness maps of MR elastography, and the diagnostic performance of MR elastography in staging liver fibrosis was evaluated by using receiver operating characteristic curve analysis and the Obuchowski measure with the histopathologic analysis of liver fibrosis in the CHB group and in the group composed of other etiologic causes. In 120 patients (97 with CHB, 23 without CHB) and 51 donors, diagnostic performance of MR elastography was validated. Results Areas under the curve of LS values for the diagnosis of significant fibrosis (>=stage F2), severe fibrosis (>=stage F3), and cirrhosis (stage F4) in the CHB group were 0.972 (95% confidence interval: 0.948, 0.987), 0.946 (95% confidence interval: 0.916, 0.968), and 0.920 (95% confidence interval: 0.885, 0.947), respectively. Obuchowski measures were similarly high in the CHB group and in the group composed of other etiologic causes (0.970 vs 0.977). However, the estimated cutoff value for stage F4 in the group with CHB was substantially lower than in the participants with other etiologic causes: 3.67 kPa versus 4.65 kPa. In the validation study for stage F1 or greater, stage F2 or greater, stage F3 or greater, and stage F4, the Youden indexes were 0.807, 0.842, 0.806, and 0.639, respectively, in the group with CHB, and 0.783, 0.900, 1.000, and 0.917, respectively, in the group without CHB. Conclusion The diagnostic performance of MR elastography in liver fibrosis staging was similarly high in the groups with and without CHB, but the cutoff LS values for diagnosing liver cirrhosis differed between the groups with and without CHB. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26844363 TI - An Electrocorticography Grid with Conductive Nanoparticles in a Polymer Thick Film on an Organic Substrate Improves CT and MR Imaging. AB - Purpose To develop an electrocorticography (ECoG) grid by using deposition of conductive nanoparticles in a polymer thick film on an organic substrate (PTFOS) that induces minimal, if any, artifacts on computed tomographic (CT) and magnetic resonance (MR) images and is safe in terms of tissue reactivity and MR heating. Materials and Methods All procedures were approved by the Animal Care and Use Committee and complied with the Public Health Services Guide for the Care and Use of Animals. Electrical functioning of PTFOS for cortical recording and stimulation was tested in two mice. PTFOS disks were implanted in two mice; after 30 days, the tissues surrounding the implants were harvested, and tissue injury was studied by using immunostaining. Five neurosurgeons rated mechanical properties of PTFOS compared with conventional grids by using a three-level Likert scale. Temperature increases during 30 minutes of 3-T MR imaging were measured in a head phantom with no grid, a conventional grid, and a PTFOS grid. Two neuroradiologists rated artifacts on CT and MR images of a cadaveric head specimen with no grid, a conventional grid, and a PTFOS grid by using a four level Likert scale, and the mean ratings were compared between grids. Results Oscillatory local field potentials were captured with cortical recordings. Cortical stimulations in motor cortex elicited muscle contractions. PTFOS implants caused no adverse tissue reaction. Mechanical properties were rated superior to conventional grids (chi(2) test, P < .05). The temperature increase during MR imaging for the three cases of no grid, PTFOS grid, and conventional grid was 3.84 degrees C, 4.05 degrees C, and 10.13 degrees C, respectively. PTFOS induced no appreciable artifacts on CT and MR images, and PTFOS image quality was rated significantly higher than that with conventional grids (two-tailed t test, P < .05). Conclusion PTFOS grids may be an attractive alternative to conventional ECoG grids with regard to mechanical properties, 3-T MR heating profile, and CT and MR imaging artifacts. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26844366 TI - Taming temptation: Visual perspective impacts consumption and willingness to pay for unhealthy foods. AB - While thinking about food is a ubiquitous facet of daily life, the perils of imaginary eating are well documented; food-related mental imagery elevates both cravings and consumption. Given the serious health issues that often arise from overeating and obesity, identifying strategies that can be used to combat the link between imagination and consumption is, therefore, of considerable theoretical and practical importance. Here we explored the possibility that a fundamental property of mental imagery-the visual perspective from which an event is viewed-may alter the appraisal of unhealthy foods. Specifically, because it is accompanied by attenuated sensorimotor activity, third-person (cf. first-person) imagery was expected to weaken the link between imagination and consumption. The results of 3 studies supported this prediction showing that third-person (cf. first-person) simulations decreased the mental representation, actual consumption, and willingness to pay for desirable items. Driving these effects was the natural reduction of sensory components furnished by third-person imagery. Together, these findings suggest that adoption of a third-person vantage point during mental imagery may be a viable and effective tactic for curbing consumption in everyday life. PMID- 26844367 TI - Vigilance in a dynamic environment. AB - Advances in technology have led to increasing levels of automation in modern work environments, moving people to the position of a passive monitor. When persons are in passive monitoring states, they are often subject to overall deficits in performance that become worse as time on task increases (i.e., vigilance decrements). Although many factors have been shown to influence whether or not a vigilance decrement will occur in a monitoring task (e.g., event rate), it is not clear how laboratory experiments translate to operational environments (Hancock, 2013). Four experiments were conducted that examined the effects of signal rate, event rate, cognitive load, training, and the presence of a dual task on performance during an air traffic control (ATC) automation failure detection task. Both failure detection and detection time were analyzed. Results from a meta-analysis revealed that cognitive load placed on participants through the use of task-relevant complex instructions produced a reliable vigilance decrement. However, other types of cognitive load did not produce any reliable vigilance decrements. The relationship of the cognitive load to the vigilance task may be an important factor in determining if the cognitive load will produce a vigilance decrement in a dynamic operational environment like air traffic control. PMID- 26844365 TI - Nanotopographical Modulation of Cell Function through Nuclear Deformation. AB - Although nanotopography has been shown to be a potent modulator of cell behavior, it is unclear how the nanotopographical cue, through focal adhesions, affects the nucleus, eventually influencing cell phenotype and function. Thus, current methods to apply nanotopography to regulate cell behavior are basically empirical. We, herein, engineered nanotopographies of various shapes (gratings and pillars) and dimensions (feature size, spacing and height), and thoroughly investigated cell spreading, focal adhesion organization and nuclear deformation of human primary fibroblasts as the model cell grown on the nanotopographies. We examined the correlation between nuclear deformation and cell functions such as cell proliferation, transfection and extracellular matrix protein type I collagen production. It was found that the nanoscale gratings and pillars could facilitate focal adhesion elongation by providing anchoring sites, and the nanogratings could orient focal adhesions and nuclei along the nanograting direction, depending on not only the feature size but also the spacing of the nanogratings. Compared with continuous nanogratings, discrete nanopillars tended to disrupt the formation and growth of focal adhesions and thus had less profound effects on nuclear deformation. Notably, nuclear volume could be effectively modulated by the height of nanotopography. Further, we demonstrated that cell proliferation, transfection, and type I collagen production were strongly associated with the nuclear volume, indicating that the nucleus serves as a critical mechanosensor for cell regulation. Our study delineated the relationships between focal adhesions, nucleus and cell function and highlighted that the nanotopography could regulate cell phenotype and function by modulating nuclear deformation. This study provides insight into the rational design of nanotopography for new biomaterials and the cell-substrate interfaces of implants and medical devices. PMID- 26844368 TI - The effect of instructor fluency on students' perceptions of instructors, confidence in learning, and actual learning. AB - Students' judgments of their own learning are often misled by perceptions of fluency-the ease with which information is presented during learning. Lectures represent important learning experiences that contain variations in fluency, but have not been extensively studied. In the current study, students watched a 22 min videotaped lecture that was delivered by the same instructor in either a fluent (strong, confident, and deliberate) manner, or in a disfluent (uncertain, hesitant, and disengaged) manner. Students then predicted their score on an upcoming test on the information, rated the instructor on traditional evaluation measures, and took a multiple-choice test on the information immediately (Experiment 1), after 10 min (Experiment 2), or after 1 day (Experiment 3). The fluent instructor was rated significantly higher than the disfluent instructor, but test scores did not consistently differ between the 2 conditions. Though students did not indicate higher confidence overall in learning from a fluent instructor, Experiment 3 found that when participants base their confidence on the instructor, those in the fluent condition were more likely to be overconfident. These findings indicate that instructor fluency leads to higher ratings of instructors and can lead to higher confidence, but it does not necessarily lead to better learning. (PsycINFO Database Record PMID- 26844369 TI - Evidence accumulation in a complex task: Making choices about concurrent multiattribute stimuli under time pressure. AB - Evidence accumulation models transform observed choices and associated response times into psychologically meaningful constructs such as the strength of evidence and the degree of caution. Standard versions of these models were developed for rapid (~1 s) choices about simple stimuli, and have recently been elaborated to some degree to address more complex stimuli and response methods. However, these elaborations can be difficult to use with designs and measurements typically encountered in complex applied settings. We test the applicability of 2 standard accumulation models-the diffusion (Ratcliff & McKoon, 2008) and the linear ballistic accumulation (LBA) (Brown & Heathcote, 2008)-to data from a task representative of many applied situations: the detection of heterogeneous multiattribute targets in a simulated unmanned aerial vehicle (UAV) operator task. Despite responses taking more than 2 s and complications added by realistic features, such as a complex target classification rule, interruptions from a simultaneous UAV navigation task, and time pressured choices about several concurrently present potential targets, these models performed well descriptively. They also provided a coherent psychological explanation of the effects of decision uncertainty and workload manipulations. Our results support the wider application of standard evidence accumulation models to applied decision-making settings. PMID- 26844371 TI - Metallic 1T-LixMoS2 Cocatalyst Significantly Enhanced the Photocatalytic H2 Evolution over Cd0.5Zn0.5S Nanocrystals under Visible Light Irradiation. AB - In the present work, metallic 1T-LixMoS2 is utilized as a novel cocatalyst for Cd0.5Zn0.5S photocatalyst. The obtained LixMoS2/Cd0.5Zn0.5S hybrids show excellent photocatalytic performance for H2 generation from aqueous solution containing Na2S and Na2SO3 under splitting visible light illumination (lambda >= 420 nm) without precious metal cocatalysts. It turns out that a certain amount of intercalating Li(+) ions ultimately drives the transition of MoS2 crystal from semiconductor triagonal phase (2H phase) to metallic phase (1T phase). The distinct properties of 1T-LixMoS2 promote the efficient separation of photoexcited electrons and holes when used as cocatalyst for Cd0.5Zn0.5S photocatalyst. As compared to 2H-MoS2 nanosheets only having edge active sites, photoinduced electrons not only transfer to the edge sites of 1T-LixMoS2, but also to the plane active sites of 1T-LixMoS2 nanosheets. The content of LixMoS2 in hybrid photocatalysts influences the photocatalytic activity. The optimal 1T LixMoS2 (1.0 wt %)/Cd0.5Zn0.5S nanojunctions display the best activity for hydrogen production, achieving a hydrogen evolution rate of 769.9 MUmol h(-1), with no use of noble metal loading, which is about 3.5 times higher than that of sole Cd0.5Zn0.5S, and 2 times higher than that of 2H-MoS2 (1.0 wt %)/Cd0.5Zn0.5S samples. Our results demonstrate that Li(+)-intercalated MoS2 nanosheets with high conductivity, high densities of active sites, low cost, and environmental friendliness are a prominent H2 evolution cocatalyst that might substitute for noble metal for potential hydrogen energy applications. PMID- 26844370 TI - Epidemiology of human leptospirosis in Malaysia, 2004-2012. AB - Leptospirosis is an emerging disease, especially in countries with a tropical climate such as Malaysia. A dramatic increase in the number of cases has been reported over the last decade; however, information on the epidemiological trends of this disease is lacking. The objective of this study is to provide an epidemiological description of human leptospirosis cases over a 9-year period (2004-2012) and disease relationship with meteorological, geographical, and demographical information. A retrospective study was undertaken to describe the patterns of human leptospirosis cases and their association with intrinsic (sex, age, and ethnicity) and extrinsic (location, rainfall, and temperature) factors. Data was grouped according to age, sex, ethnicity, seasonality and geographical distribution, and analyzed using statistical tools to understand the influence of all the different factors on disease incidence. A total of 12,325 cases of leptospirosis were reported between 2004 and 2012 with an upward trend in disease incidence, with the highest in 2012. Three hundred thirty-eight deaths were reported with an overall case fatality rate of 2.74%, with higher incidence in males (9696; 78.7%) compared with female patients (2629; 21.3%), and overall male to female ratio of 3.69:1. Patients aged cohorts between 30-39 years old (16.22 per 100,000 population) had the highest disease incidence while the lowest incidence occurred between <1 to 9 years old (3.44 per 100,000 population). The average incidence was highest amongst Malays (10.97 per 100,000 population), followed by Indians (7.95 per 100,000 population). Stratification according to geographical distribution showed that the state of Malacca had the highest average disease incidence (11.12 per 100,000 population) followed by Pahang (10.08 per 100,000 population). The states of Terengganu, Kelantan, and Perak recorded similar rates of incidence (~8.00 per 100,000 population), while Johor with the least number of reported cases (1.80 per 100,000 population). Positive relationships were recorded between the number of reported cases with the number of raining days per month and monthly average temperature (p-value<0.05). However, no significant association was noted between rainfall volume and number of reported Leptospirosis cases. This collaborative efforts between medical, academic and governmental institutions has enabled the construction of this comprehensive database that is essential to understand the disease trends in Malaysia and add insights into the prevention and control of this disease. PMID- 26844372 TI - Polyvinylpyrrolidone-Poly(ethylene glycol) Modified Silver Nanorods Can Be a Safe, Noncarrier Adjuvant for HIV Vaccine. AB - One of the biggest obstacles for the development of HIV vaccines is how to sufficiently trigger crucial anti-HIV immunities via a safe manner. We herein integrated surface modification-dependent immunostimulation against HIV vaccine and shape-dependent biosafety and designed a safe noncarrier adjuvant based on silver nanorods coated by both polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG). Such silver nanorods can significantly elevate crucial immunities of HIV vaccine and overcome the toxicity, which is a big problem for other existing adjuvants. This study thus provided a principle for designing a safe and high efficacy material for an adjuvant and allow researchers to really have a safe and effective prophylaxis against HIV. We expect this material approach to be applicable to other types of vaccines, whether they are preventative or therapeutic. PMID- 26844373 TI - Assessment of Predictive Response Factors to Intragastric Balloon Therapy for the Treatment of Obesity. AB - BACKGROUND: Obesity is a worldwide epidemic that is difficult to control with non invasive treatments, which usually present poor results. In this context, the intragastric balloon (IGB) is an important tool that presents a mean body weight loss (BWL) estimated at approximately 12%, although individual responses are highly variable. OBJECTIVES: This study assesses whether there are factors that can predict responses to IGB therapy either before or early after placement of the device. MATERIALS AND METHODS: A total of 50 obese patients underwent insertion of IGB placed endoscopically, and patients were monitored for 6 months. The evaluated predictive factors involved general characteristics and psychological, social, and dyspeptic aspects, and the preliminary results obtained in the first month after balloon placement. RESULTS: The mean weight loss was 11.5%, and 48% of the participants presented BWL >10%. Among the factors analyzed before IGB placement, only advanced age (P = .04) and higher scores obtained in the social relationships domain of a shorter version of the World Health Organization's Quality of Life questionnaire (P = .02) were significant. Analysis of the factors evaluated after IGB placement revealed that the BWL amounts observed in week 2 (P = .001) and week 4 (P < .001) and the intensity of dyspeptic symptoms in week 2 (P < .001) were positive predictive factors. CONCLUSIONS: The assessment of predictive factors may help to manage patients with IGB. PMID- 26844374 TI - Microglia: A Unique Versatile Cell in the Central Nervous System. AB - Microglia are the resident monocytic cells in the central nervous system (CNS), where they constitute the complex tissue structure together with a diverse set of cell-types, including neurons, glial cells, and vasculature. Different from other cells, microglia have distinct features, including not only their origin but functions in the CNS, and serve multiple roles within healthy and diseased CNS tissue. The present review highlights the latest advance in our understanding of the nature of microglia in the CNS, from their origin to both the physiological and pathological roles throughout their whole life. PMID- 26844376 TI - Directly Insight Into the Inter- and Intramolecular Interactions of CL-20/TNT Energetic Cocrystal through the Theoretical Simulations of THz Spectroscopy. AB - Compared with cocrystal coformers, an explosive cocrystal has distinctive packing arrangements and complex intermolecular interactions. Identifying the spectral signatures of an explosive cocrystal and understanding the molecular low frequency modes by means of the spectrum in the terahertz range are of great worth to the explicit mechanism of cocrystal formation. In this work, on the basis of the joint molecular dynamics (MD) simulations and solid-state density functional theory (DFT) calculations, we have investigated the terahertz (THz) absorption spectra of the CL-20/TNT cocrystal and its different directions as well as cocrystal coformers and determined the systematic and all-sided assignments of corresponding THz vibration modes. The THz spectral comparison of the cocrystal with different directions and the cocrystal coformers indicates that the CL-20/TNT cocrystal has five fresh low-frequency absorption features as unique and discernible peaks for identification, in which 0.25, 0.73, and 0.87 THz are attributed to intensive crystalline vibrations; 0.87 THz is also caused by C-H...O hydrogen-bonding bending vibrations; 1.60 and 1.85 THz features originate from C-H...O hydrogen-bond stretching vibrations. Additionally, the THz spectrum of the (001) direction of the CL-20/TNT cocrystal verifies that the molecular conformation of the CL-20 is the same as that in the beta-polymorph, other than the initial conformation of raw material epsilon-CL-20. PMID- 26844375 TI - Gonadal Hormones Rapidly Enhance Spatial Memory and Increase Hippocampal Spine Density in Male Rats. AB - 17beta-estradiol (E2) rapidly, within minutes, activates behaviors and cognition by binding to membrane estrogen receptors, activating cell signaling cascades and increasing dendritic spines. In female rodents, E2 enhances spatial memory within 2-4 hours, and spine density is increased in the CA1 area of the hippocampus within 30-60 minutes. Although chronic gonadal hormone treatments in male rats alter cognition and spines/spine synapses and acute hormone effects occur in hippocampal slices, effects of acute, in vivo hormone administration in males are unknown. Therefore, we assessed rapid effects of E2 (20 MUg/kg) and testosterone (T) (750 MUg/kg) on spatial memory using the object placement task and on hippocampal spine density using Golgi impregnation. Orchidectomized rats received hormones immediately after the training trial and were tested for retention 2 hours later. Vehicle-injected orchidectomized males spent equal time exploring objects in the old and new locations, but E2- or T-treated subjects spent more time exploring objects at the new location, suggesting enhanced memory. Both hormones also increased spine density in CA1, but not the dentate gyrus, by 20% 40% at 30 minutes and 2 hours after injections. This report is the first, to our knowledge, to show E2 and T enhancements of memory and spine density within such a short time frame in male rats. PMID- 26844377 TI - Nongenomic actions of neurosteroid pregnenolone and its metabolites. AB - Steroids have been widely used in the clinical setting. They bind and activate nuclear receptors to regulate gene expression. In addition to activating genomic transcription, steroids also exert nongenomic actions. The current article focuses on the nongenomic actions of neurosteroids, including pregnenolone (P5), 7alpha-hydroxypregnenolone, pregnenolone sulfate and allopregnanolone. Pregnenolone and its derivatives promote neuronal activity by enhancing learning and memory, relieving depression, enhancing locomotor activity, and promoting neuronal cell survival. They exert these effects by activating various target proteins located in the cytoplasm or cell membrane. Pregnenolone and its metabolites bind to receptors such as microtubule-associated proteins and neurotransmitter receptors to elicit a series of reactions including stabilization of microtubules, increase of ion flux into cells, and dopamine release. The wide actions of neurosteroids indicate that pregnenolone derivatives have great potential in future treatment of neurological diseases. PMID- 26844378 TI - Metabolic, enzymatic and gene involvement in cerebral glucose dysmetabolism after traumatic brain injury. AB - In this study, the metabolic, enzymatic and gene changes causing cerebral glucose dysmetabolism following graded diffuse traumatic brain injury (TBI) were evaluated. TBI was induced in rats by dropping 450g from 1 (mild TBI; mTBI) or 2m height (severe TBI; sTBI). After 6, 12, 24, 48, and 120h gene expressions and enzymatic activities of glycolysis and pentose phosphate pathway (PPP) enzymes, and levels of lactate, ATP, ADP, ATP/ADP (indexing mitochondrial phosphorylating capacity), NADP(+), NADPH and GSH were determined in whole brain extracts (n=9 rats at each time for both TBI levels). Sham-operated animals (n=9) were used as controls. Results demonstrated that mTBI caused a late increase (48-120h post injury) of glycolytic gene expression and enzymatic activities, concomitantly with mitochondrial functional recovery (ATP and ATP/ADP normalization). No changes in lactate and PPP genes and enzymes, were accompanied by transient decrease in GSH, NADP(+), NADPH and NADPH/NADP(+). Animals following sTBI showed early increase (6-24h post injury) of glycolytic gene expression and enzymatic activities, occurring during mitochondrial malfunctioning (50% decrease in ATP and ATP/ADP). Higher lactate and lower GSH, NADP(+), NADPH, NADPH/NADP(+) than controls were recorded at anytime post injury (p<0.01). Both TBI levels caused metabolic and gene changes affecting glucose metabolism. Following mTBI, increased glucose flux through glycolysis is coupled to mitochondrial glucose oxidation. "True" hyperglycolysis occurs only after sTBI, where metabolic changes, caused by depressed mitochondrial phosphorylating capacity, act on genes causing net glycolytic flux increase uncoupled from mitochondrial glucose oxidation. PMID- 26844379 TI - Adaptation within mitochondrial oxidative phosphorylation supercomplexes and membrane viscosity during degeneration of dopaminergic neurons in an animal model of early Parkinson's disease. AB - In Parkinson's disease (PD) motor symptoms are not observed until loss of 70% of dopaminergic neurons in substantia nigra (SN), preventing early diagnosis. Mitochondrial dysfunction was indicated in neuropathological process already at early PD stages. Aging and oxidative stress, the main factors in PD pathogenesis, cause membrane stiffening, which could influence functioning of membrane-bound oxidative phosphorylation (OxPhos) complexes (Cxs) in mitochondria. In 6-OHDA rat model, medium-sized dopaminergic lesion was used to study mitochondrial membrane viscosity and changes at the level of OxPhos Cxs and their higher assembled states-supercomplexes (SCxs), during the early degeneration processes and after it. We observed loss of dopaminergic phenotype in SN and decreased dopamine level in striatum (STR) before actual death of neurons in SN. Behavioural deficits induced by lesion were reversed despite progressing neurodegeneration. Along with degeneration process in STR, mitochondrial Cx I performance and amount decreased in almost all forms of SCxs. Also, progressing decrease of Cx IV performance in SCxs (I1III2IV3-1, I1IV2-1) in STR was observed during degeneration. In SN, SCxs containing Cx I increased protein amount and a shifted individual Cx I1 into superassembled states. Importantly, mitochondrial membrane viscosity changed in parallel with altered SCxs performance. We show for the first time changes at the level of mitochondrial membrane viscosity influencing SCxs function after dopaminergic system degeneration. It implicates that altered mitochondrial membrane viscosity could play an important role in regulation of mitochondria functioning and pathomechanisms of PD. The data obtained are also discussed in relation to compensatory processes observed. PMID- 26844380 TI - pTop 1.0: A High-Accuracy and High-Efficiency Search Engine for Intact Protein Identification. AB - There has been tremendous progress in top-down proteomics (TDP) in the past 5 years, particularly in intact protein separation and high-resolution mass spectrometry. However, bioinformatics to deal with large-scale mass spectra has lagged behind, in both algorithmic research and software development. In this study, we developed pTop 1.0, a novel software tool to significantly improve the accuracy and efficiency of mass spectral data analysis in TDP. The precursor mass offers crucial clues to infer the potential post-translational modifications co occurring on the protein, the reliability of which relies heavily on its mass accuracy. Concentrating on detecting the precursors more accurately, a machine learning model incorporating a variety of spectral features was trained online in pTop via a support vector machine (SVM). pTop employs the sequence tags extracted from the MS/MS spectra and a dynamic programming algorithm to accelerate the search speed, especially for those spectra with multiple post-translational modifications. We tested pTop on three publicly available data sets and compared it with ProSight and MS-Align+ in terms of its recall, precision, running time, and so on. The results showed that pTop can, in general, outperform ProSight and MS-Align+. pTop recalled 22% more correct precursors, although it exported 30% fewer precursors than Xtract (in ProSight) from a human histone data set. The running speed of pTop was about 1 to 2 orders of magnitude faster than that of MS Align+. This algorithmic advancement in pTop, including both accuracy and speed, will inspire the development of other similar software to analyze the mass spectra from the entire proteins. PMID- 26844381 TI - Self-Assembly of Tetraphenyldibenzoperiflanthene (DBP) Films on Ag(111) in the Monolayer Regime. AB - Tetraphenyldibenzoperiflanthene (DBP) is a promising candidate as a component of highly efficient organic photovoltaic cells and organic light-emitting diodes. The structural properties of thin films of this particular lander-type molecule on Ag(111) were investigated by complementary techniques. Highly ordered structures were obtained, and their mutual alignment was characterized by means of low-energy electron diffraction (LEED). Scanning tunneling microscopy (STM) images reveal two slightly different arrangements within the first monolayer (ML), both describable as specific herringbone patterns with two molecules per unit cell whose dibenzoperiflanthene framework is parallel to the surface. In contrast, single DBP molecules in the second ML were imaged with much higher intramolecular resolution, resembling the shape of the frontier orbitals in the gas phase as calculated by means of density functional theory (DFT). Further deposition leads to the growth of highly ordered bilayer islands on top of the first ML with identical unit cell dimensions and orientation but slightly inclined molecules. This suggests that the first ML acts as a template for the epitaxial growth of further layers. Simultaneously, a significant number of second-layer molecules mainly located at step edges or scattered over narrow terraces do not form highly ordered aggregates. PMID- 26844383 TI - Correction to Tetraphenylhexaazaanthracenes: 16pi Weakly Antiaromatic Species with Singlet Ground States. PMID- 26844382 TI - Determining Factors of Lipophilic Micronutrient Bioaccessibility in Several Leafy Vegetables. AB - Micronutrient deficiencies are still a public health issue in least developed countries. Promoting diet diversification is a promising strategy. Numerous fruits and vegetables are rich in micronutrients, but some of these compounds are poorly bioaccessible. The objective of this study was to identify the biochemical determinants of the micronutrient bioaccessibility in leaves. The contents in cell walls, pectins, tannins, and proteins of the leafy vegetables were assessed, and correlations with the micronutrient bioaccessibitity were explored. The leafy vegetables have interesting nutritional profiles with noticeable amounts in protein, provitamin A (beta-carotene), and alpha-tocopherol for some species. Their cell wall contents greatly varied from 3.4 to 8.7 g/100 g as well as their pectin percentages. Only the perilla and drumstick leaves contained condensed tannins. In fresh leaves, the contents in bioaccessible carotenoids were low. The correlation study highlighted that the carotenoid bioaccessibility was negatively correlated to the pectin contents of the leaves. PMID- 26844384 TI - Cyclosporine-A mimicked the ischemic pre- and postconditioning-mediated cardioprotection in hypertensive rats: Role of PKCepsilon. AB - Our aim was to assess the action of cyclosporine-A (CsA) against reperfusion injury in spontaneously hypertensive rats (SHR) compared to the effects of ischemic pre- (IP) and postconditioning (IPC), examining the role played by PKCepsilon. Isolated hearts were submitted to the following protocols: IC: 45 min global ischemia (GI) and 1h reperfusion (R); IP: a cycle of 5 min GI and 10 min of R prior to 45 min-GI; and IPC: three cycles of 30s-GI/30s-R at the start of R. Other hearts of the IC, IP and IPC groups received CsA (mitochondrial permeability transition pore inhibitor) or chelerythrine (Che, non-selective PKC inhibitor). Infarct size (IS) was assessed. TBARS and reduced glutathione (GSH) content - as parameters of oxidative damage, the expression of P-Akt, P-GSK 3beta, P-PKCepsilon and cytochrome c (Cyc) release - as an index of mitochondrial permeability and the response of isolated mitochondria to Ca(2+) were also measured. IS similarly decreased in preconditioned, postconditioned and CsA treated heart showing the highest values in the combinations IP+CsA and IPC+CsA. TBARS decreased and GSH was partially preserved after all interventions. The content of P-Akt, P-GSK-3beta and P-PKCepsilon increased in cytosol and decreased in mitochondria after IP and IPC. In CsA treated hearts these enzymes increased in both fractions reaching the highest values. Cyc release was attenuated and the response of mitochondria to Ca(2+) was improved by the interventions. The beneficial effects of IP and IPC were annulled when PKC was inhibited with Che. A PKCepsilon/VDAC association was also detected. These data show that, in SHR, the CsA treatment mimicked and reinforced the cardioprotective action afforded by IP and IPC in which PKCepsilon-mediated attenuation of mitochondrial permeability appears as the main mechanism involved. PMID- 26844385 TI - Case Report of an Hepatoid Adenocarcinoma of the Stomach. AB - Hepatoid adenocarcinoma (HAC) is a rare but important type of extrahepatic tumor that has a morphologic similarity to hepatocellular carcinoma, with production of alpha-fetoprotein in high amounts and a poor prognosis. Stomach is one of the organs in which HAC has been most commonly identified. We report a case of an old man with a polypoid mass in the prepyloric region. The microscopical aspects were suggestive for an undifferentiated adenocarcinoma, but the positive immunohistochemical staining for alpha-fetoprotein, alpha-1-antitrypsin, alpha-1 antichymotrypsin, and Hep Par1 were crucial for the final diagnosis of hepatoid adenocarcinoma of the stomach. Because of the poor prognosis for this type of tumor, correct and early-stage diagnosis of HAC is essential and long-term follow up is required. PMID- 26844386 TI - Expression of MUC1 by Merkel Cell Carcinoma is not Dependent on Merkel Cell Polyomavirus Infection. PMID- 26844387 TI - Strategies in probabilistic feedback learning in Parkinson patients OFF medication. AB - Studies on classification learning suggested that altered dopamine function in Parkinson's Disease (PD) specifically affects learning from feedback. In patients OFF medication, enhanced learning from negative feedback has been described. This learning bias was not seen in observational learning from feedback, indicating different neural mechanisms for this type of learning. The present study aimed to compare the acquisition of stimulus-response-outcome associations in PD patients OFF medication and healthy control subjects in active and observational learning. 16 PD patients OFF medication and 16 controls were examined with three parallel learning tasks each, two feedback-based (active and observational) and one non feedback-based paired associates task. No acquisition deficit was seen in the patients for any of the tasks. More detailed analyses on the learning strategies did, however, reveal that the patients showed more lose-shift responses during active feedback learning than controls, and that lose-shift and win-stay responses more strongly determined performance accuracy in patients than controls. For observational feedback learning, the performance of both groups correlated similarly with the performance in non-feedback-based paired associates learning and with the accuracy of observed performance. Also, patients and controls showed comparable evidence of feedback processing in observational learning. In active feedback learning, PD patients use alternative learning strategies than healthy controls. Analyses on observational learning did not yield differences between patients and controls, adding to recent evidence of a differential role of the human striatum in active and observational learning from feedback. PMID- 26844388 TI - CRTC1 nuclear localization in the hippocampus of the pilocarpine-induced status epilepticus model of temporal lobe epilepsy. AB - cAMP response-element binding protein (CREB)-dependent genes are differentially expressed in brains of temporal lobe epilepsy (TLE) patients and also in animal models of TLE. Previous studies have demonstrated the importance of CREB regulated transcription in TLE. However, the role of the key regulator of CREB activity, CREB-regulated transcription coactivator 1 (CRTC1), has not been explored in epilepsy. In the present study the pilocarpine-induced status epilepticus (SE) model of TLE was used to study the regulation of CRTC1 during and following SE. Nuclear translocation of CRTC1 is critical for its transcriptional activity, and dephosphorylation at serine 151 residue via calcineurin phosphatase regulates cytoplasmic to nuclear transit of CRTC1. Here, we examined the localization and phosphorylation (Ser151) of CRTC1 in SE-induced rat hippocampus at two different time points after SE onset. One hour after SE onset, we found that CRTC1 translocates to the nucleus of CA1 neurons but not CA3 or dentate granule neurons. We further found that this CRTC1 nuclear localization is independent of Ser151 dephosphorylation since we did not detect any difference in dephosphorylation of Ser151 between control and SE animals at this time point. In contrast, 48 h after SE CRTC1 shows increased nuclear localization in the dentate gyrus (DG) of the SE-induced rats. At 48 h after SE, FK506 treatment blocked CRTC1 nuclear localization and dephosphorylation of Ser151. Our results provide evidence that CREB cofactor CRTC1 translocates into the nucleus of a distinct subset of hippocampal neurons during and following SE and this translocalization is regulated by calcineurin at a later time point following SE. Nuclear CRTC1 can bind to CREB possibly altering transcription during epileptogenesis. PMID- 26844390 TI - Age-related audiovisual interactions in the superior colliculus of the rat. AB - It is well established that multisensory integration is a functional characteristic of the superior colliculus that disambiguates external stimuli and therefore reduces the reaction times toward simple audiovisual targets in space. However, in a condition where a complex audiovisual stimulus is used, such as the optical flow in the presence of modulated audio signals, little is known about the processing of the multisensory integration in the superior colliculus. Furthermore, since visual and auditory deficits constitute hallmark signs during aging, we sought to gain some insight on whether audiovisual processes in the superior colliculus are altered with age. Extracellular single-unit recordings were conducted in the superior colliculus of anesthetized Sprague-Dawley adult (10-12 months) and aged (21-22 months) rats. Looming circular concentric sinusoidal (CCS) gratings were presented alone and in the presence of sinusoidally amplitude modulated white noise. In both groups of rats, two different audiovisual response interactions were encountered in the spatial domain: superadditive, and suppressive. In contrast, additive audiovisual interactions were found only in adult rats. Hence, superior colliculus audiovisual interactions were more numerous in adult rats (38%) than in aged rats (8%). These results suggest that intersensory interactions in the superior colliculus play an essential role in space processing toward audiovisual moving objects during self-motion. Moreover, aging has a deleterious effect on complex audiovisual interactions. PMID- 26844391 TI - Critical assessment of the pH of children's soap. AB - OBJECTIVE: To evaluate the pH value of children's antibacterial soaps and syndets used in children's baths and verify whether there is information regarding pH on the product label. METHODS: Quantitative, cross-sectional, analytical observational study that included ninety soap samples, both in bar and liquid presentations, as follows: 67 children's soap (group 1), 17 antibacterial soaps (group 2), and 6 syndets (group 3). Each sample had its pH measured after 1% dilution. In addition to descriptive statistics, the Pearson-Yates chi-squared test and Student's t-tests were applied, considering the minimal significance level of 5%. The Wilcoxon-Mann-Whitney test, Fisher's exact test, and the Kruskal Wallis test were used for inferential statistics. RESULTS: The pH levels varied considerably between liquid and bar presentations, with lower levels (4.4-7.9) found for the liquids (p<0.05). Syndets showed pH levels close to the ideal (slightly acid) and the antibacterial soaps showed the highest pH levels (up to 11.34) (p<0.05). Only two of the soaps included in the study had information about their pH levels on the product packaging. CONCLUSIONS: Knowledge of the pH of children's soap by doctors and users is important, considering the great pH variability found in this study. Moreover, liquid soaps, and especially syndets, are the most recommended for the sensitive skin of neonates and infants, in order to guarantee skin barrier efficacy. PMID- 26844392 TI - Nutritional management and postoperative prognosis of newborns submitted to primary surgical repair of gastroschisis. AB - OBJECTIVE: Gastroschisis is a defect of the abdominal wall, resulting in congenital evisceration and requiring neonatal intensive care, early surgical correction, and parenteral nutrition. This study evaluated newborns with gastroschisis, seeking to associate nutritional characteristics with time of hospital stay. METHODS: This was a retrospective cohort study of 49 newborns undergoing primary repair of gastroschisis between January 1995 and December 2010. The newborns' characteristics were described with emphasis on nutritional aspects, correlating them with length of hospital stay. RESULTS: The characteristics that influenced length of hospital stay were: (1) newborn small for gestational age (SGA); (2) use of antibiotics; (3) day of life when enteral feeding was started; (4) day of life when full diet was reached. SGA infants had longer length of hospital stay (24.2%) than other newborns. The length of hospital stay was increased by 2.1% for each additional day taken to introduce enteral feeding. However, slower onset of full enteral feeding acted as a protective factor, decreasing length of stay by 3.6%. The volume of waste drained by the stomach catheter in the 24h prior the start of enteral feeding was not associated with the timing of diet introduction or length of hospital stay. CONCLUSION: Early start of enteral feeding and small, gradual increase of volume can shorten the use of parenteral nutrition. This management strategy contributes to reduce the incidence of infection and length of hospital stay of newborns with gastroschisis. PMID- 26844393 TI - Nanocellulose/nanobentonite composite anchored with multi-carboxyl functional groups as an adsorbent for the effective removal of Cobalt(II) from nuclear industry wastewater samples. AB - A novel adsorbent, poly(itaconic acid/methacrylic acid)-grafted nanocellulose/nanobentonite composite [P(IA/MAA)-g-NC/NB] with multi carboxyl functional groups for the effective removal of Cobalt(II) [Co(II)] from aqueous solutions. The adsorbent was characterized using FTIR, XRD, SEM-EDS, AFM and potentiometric titrations before and after adsorption of Co(II) ions. FTIR spectra revealed that Co(II) adsorption on to the polymer may be due to the involvement of COOH groups. The surface morphological changes were observed by the SEM images. The pH was optimized as 6.0. An adsorbent dose of 2.0g/L found to be sufficient for the complete removal of Co(II) from 100mg/L at room temperature. Pseudo-first-order and pseudo-second-order models were tested to describe kinetic data and adsorption of Co(II) follows pseudo-second-order model. The equilibrium attained at 120min. Isotherm studies were conducted and data were analyzed using Langmuir, Freundlich and Sips isotherm models and best fit was Sips model. Thermodynamic study confirmed endothermic and physical nature of adsorption of the Co(II) onto the adsorbent. Desorption experiments were done with 0.1MHCl proved that without significant loss in performance adsorbent could be reused for six cycles. The practical efficacy and effectiveness of the adsorbent were tested using nuclear industrial wastewater. A double stage batch adsorption system was designed from the adsorption isotherm data of Co(II) by constructing operating lines. PMID- 26844389 TI - Sex-dependent programming effects of prenatal glucocorticoid treatment on the developing serotonin system and stress-related behaviors in adulthood. AB - Prenatal stress and overexposure to glucocorticoids (GC) during development may be associated with an increased susceptibility to a number of diseases in adulthood including neuropsychiatric disorders, such as depression and anxiety. In animal models, prenatal overexposure to GC results in hyper-responsiveness to stress in adulthood, and females appear to be more susceptible than males. Here, we tested the hypothesis that overexposure to GC during fetal development has sex specific programming effects on the brain, resulting in altered behaviors in adulthood. We examined the effects of dexamethasone (DEX; a synthetic GC) during prenatal life on stress-related behaviors in adulthood and on the tryptophan hydroxylase-2 (TpH2) gene expression in the adult dorsal raphe nucleus (DRN). TpH2 is the rate-limiting enzyme for serotonin (5-HT) synthesis and has been implicated in the etiology of human affective disorders. Timed-pregnant rats were treated with DEX from gestational days 18-22. Male and female offspring were sacrificed on the day of birth (postnatal day 0; P0), P7, and in adulthood (P80 84) and brains were examined for changes in TpH2 mRNA expression. Adult animals were also tested for anxiety- and depressive- like behaviors. In adulthood, prenatal DEX increased anxiety- and depressive- like behaviors selectively in females, as measured by decreased time spent in the center of the open field and increased time spent immobile in the forced swim test, respectively. Prenatal DEX increased TpH2 mRNA selectively in the female caudal DRN at P7, whereas it decreased TpH2 mRNA selectively in the female caudal DRN in adulthood. In animals challenged with restraint stress in adulthood, TpH2 mRNA was significantly lower in rostral DRN of prenatal DEX-treated females compared to vehicle-treated females. These data demonstrated that prenatal overexposure to GC alters the development of TpH2 gene expression and these alterations correlated with lasting behavioral changes found in adult female offspring. PMID- 26844394 TI - Biosynthesis of the Metalloclusters of Nitrogenases. AB - Nitrogenase is a versatile metalloenzyme that is capable of catalyzing two important reactions under ambient conditions: the reduction of nitrogen (N2) to ammonia (NH3), a key step in the global nitrogen cycle; and the reduction of carbon monoxide (CO) and carbon dioxide (CO2) to hydrocarbons, two reactions useful for recycling carbon waste into carbon fuel. The molybdenum (Mo)- and vanadium (V)-nitrogenases are two homologous members of this enzyme family. Each of them contains a P-cluster and a cofactor, two high-nuclearity metalloclusters that have crucial roles in catalysis. This review summarizes the progress that has been made in elucidating the biosynthetic mechanisms of the P-cluster and cofactor species of nitrogenase, focusing on what is known about the assembly mechanisms of the two metalloclusters in Mo-nitrogenase and giving a brief account of the possible assembly schemes of their counterparts in V-nitrogenase, which are derived from the homology between the two nitrogenases. PMID- 26844395 TI - Macrodomains: Structure, Function, Evolution, and Catalytic Activities. AB - Recent developments indicate that macrodomains, an ancient and diverse protein domain family, are key players in the recognition, interpretation, and turnover of ADP-ribose (ADPr) signaling. Crucial to this is the ability of macrodomains to recognize ADPr either directly, in the form of a metabolic derivative, or as a modification covalently bound to proteins. Thus, macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response. Their importance is further indicated by the fact that dysregulation or mutation of a macrodomain is associated with several diseases, including cancer, developmental defects, and neurodegeneration. In this review, we summarize the current insights into macrodomain evolution and how this evolution influenced their structural and functional diversification. We highlight some aspects of macrodomain roles in pathobiology as well as their emerging potential as therapeutic targets. PMID- 26844397 TI - Novobiocin binding to NalD induces the expression of the MexAB-OprM pump in Pseudomonas aeruginosa. AB - NalD was reported to be the secondary repressor of the MexAB-OprM multidrug efflux pump, the major system contributing to intrinsic multidrug resistance in Pseudomonas aeruginosa. Here, we show that novobiocin binds directly to NalD, which leads NalD to dissociate from the DNA promoter, and thus de-represses the expression of the MexAB-OprM pump. In addition, we have solved the crystal structure of NalD at a resolution of 2.90 A. The structural alignment of NalD to its homologue TtgR reveals that the residues N129 and H167 in NalD are involved in its novobiocin-binding ability. We have confirmed the function of these two amino acids by EMSA and plate assay. The results presented here highlight the importance and diversity of regulatory mechanism in bacterial antibiotic resistance, and provide further insight for novel antimicrobial development. PMID- 26844398 TI - Death in a legal poppy field in Spain. AB - Opium is a substance extracted from Papaver somniferum L. Opium latex contains morphine, codeine, and thebaine and non-analgesic alkaloids such as papaverine and noscapine. In Spain opium growing is allowed only for scientific or pharmaceutical purposes and harvest is supervised by the Spanish Health Ministry. This work describes a sudden fatality involving opium consumption in a legal poppy field. The toxicological and autopsy findings, previous disease, paraphernalia, and scenario are discussed in order to clarify cause and manner of death. A 32-year-old white caucasian male was found unresponsive in a legal poppy field in the South of Spain. The emergency medical services responded to the scene where he was pronounced dead. The friends explained that the deceased had presented with about 30min of convulsions; in spite of trying to keep his airway tract open they noted that "he stayed airless". According to them the victim suffered from epilepsy. Tools found beside his body consisted of plain wood sticks with a blade razor, a fabric handle, and paper. A comprehensive toxicological screening for abuse and psychoactive drugs was performed in the deceased samples. This included ethanol and volatile analysis by HS-GC-FID in peripheral blood and urine, enzyme immunoassay in urine by CEDIA, and a basic drug screening in all samples (including paraphernalia) by GC-MS using modes full scan for screening/confirmation and selected ion monitoring for quantitation. The peripheral blood, urine, vitreous, and gastric content contained the following concentrations of opiates expressed in mg/L (gastric content additionally also expressed in mg total): 0.10, 7.12, 0.23, and 14.80 (2.81mg total) of thebaine, 0.13, 4.50, 0.13, and 6.60 (1.25mg total) of morphine (free), 0.48, 0.88, 0.17, and 1.50 (0.28mg total) of codeine. These tree opiates were also detected in the tools (paraphernalia) used by the deceased for opium consumption. Other toxicological findings were metabolites of cocaine and cannabis. Apparently the victim stole poppy capsules and ingested an unknown quantity of the latex with the goal to obtain euphoric effects. The cause of death was considered poly-drug toxicity with a preponderant role of thebaine and morphine. In addition, the epileptic condition of the deceased could have played a role. As far as we know, there are no previous reports of fatalities occurring in legal poppy fields. PMID- 26844399 TI - Clinical prospective evaluation of zirconia-based three-unit posterior fixed dental prostheses: Up-to ten-year results. AB - OBJECTIVES: Only a few studies exist, which assess the clinical long-term behavior of all-ceramic FDPs in the posterior region. The aim of the present prospective clinical study was to evaluate the clinical performance of posterior three-unit FDPs manufactured from Y-TZP after a service period up to 10 years. METHODS: 55 patients received 59 three-unit FDPs in the posterior region of the maxilla or mandible. Abutment teeth were prepared and full-arch impressions were taken. Definitive casts were fabricated and optically scanned. Frameworks were fabricated with computer-aided design (CAD) and manufacturing (CAM) technology. Y TZP frameworks were veneered and adhesively luted to the abutment teeth. Baseline and follow-up examinations (service time: >= 48 months) were recorded by applying modified United States Public Health Services (USPHS) rating criteria. Cumulative survival rate was analyzed with Kaplan-Meier. Percentage of biological and technical complication was calculated. RESULTS: Fifty-three patients with 57 FDPs attended the last follow-up visit and a mean observation period of the remaining was 6.3 +/- 1.9 years was calculated. Biological complications occurred in 17.5%, technical complications in 28% of the FDPs. The 10-year cumulative survival rate amounted 85.0%. Three FDPs failed to survive, two due to a root fracture of the abutment tooth and one due to secondary caries. CONCLUSIONS: Three-unit FDPs made from Y-TZP, veneered with ceramic offer a treatment option with a high rate of chipping. However, the manufacturing processes nowadays are modified in order to avoid this complication. CLINICAL SIGNIFICANCE: The results of the present investigation suggest that three-unit Y-TZP posterior FDPs may are a possible treatment option. However, a high rate of chipping can be expected. PMID- 26844400 TI - Artesunate demonstrates in vitro synergism with several antiviral agents against human cytomegalovirus. AB - BACKGROUND: Human cytomegalovirus (HCMV) infections remain a major problem in immunocompromised patients. Three antiviral agents, ganciclovir (GCV), foscarnet (FOS) and cidofovir (CDV), are currently approved for the treatment of HCMV infections. They all target the viral DNA polymerase and are associated with significant side effects. Combinations of novel antiviral compounds acting on different targets such as artesunate (ART) with currently approved drugs or eventually letermovir or maribavir (MBV) may result in synergistic effects. Here, we evaluated the in vitro activity of a series of two-drug combinations against a wild-type recombinant HCMV strain by the Gaussia luciferase (GLuc) reporter assay. METHODS: The in vitro activity of each drug was first tested individually against HCMV by using the GLuc reporter assay. The activity of two-drug combinations consisting of ART and currently approved drugs, as well as letermovir or MBV, was then analysed by the Chou-Talalay method. RESULTS: The concentrations of GCV, FOS, CDV and ART that reduced the GLuc activity by 50% (EC50 values) were 3.92 +/-1.64 uM, 62.45 +/-8.39 uM, 0.68 +/-0.19 uM and 3.86 +/ 1.25 uM, respectively, whereas those of MBV and letermovir were 64 +/-22 nM and 2.50 +/-0.83 nM, respectively. The combination of ART with GCV, CDV or MBV was associated with synergism, whereas combination of ART with FOS or letermovir resulted in moderate synergism. As expected, the combination of MBV with GCV was antagonistic. CONCLUSIONS: These results suggest that the combination of ART with the antiviral agents tested in this study could be an interesting strategy for the treatment of HCMV infections to reduce toxicity and drug-resistance development. PMID- 26844402 TI - Continuous reduction of cyclic adsorbed and desorbed NO(x) in diesel emission using nonthermal plasma. AB - Considering the recent stringent regulations governing diesel NO(x) emission, an aftertreatment system for the reduction of NO(x) in the exhaust gas has been proposed and studied. The proposed system is a hybrid method combining nonthermal plasma and NOx adsorbent. The system does not require precious metal catalysts or harmful chemicals such as urea and ammonia. In the present system, NO(x) in diesel emission is treated by adsorption and desorption by adsorbent as well as nonthermal plasma reduction. In addition, the remaining NO(x) in the adsorbent is desorbed again in the supplied air by residual heat. The desorbed NO(x) in air recirculates into the intake of the engine, and this process, i.e., exhaust gas components' recirculation (EGCR) achieves NO(x) reduction. Alternate utilization of two adsorption chambers in the system can achieve high-efficiency NO(x) removal continuously. An experiment with a stationary diesel engine for electric power generation demonstrates an energy efficiency of 154 g(NO2)/kWh for NO(x) removal and continuous NO(x) reduction of 70.3%. Considering the regulation against diesel emission in Japan, i.e., the new regulation to be imposed on vehicles of 3.5-7.5 ton since 2016, the present aftertreatment system fulfills the requirement with only 1.0% of engine power. PMID- 26844401 TI - A Modified Preauricular Approach for Treating Intracapsular Condylar Fractures to Prevent Facial Nerve Injury: The Supratemporalis Approach. AB - PURPOSE: The facial nerve remains at risk of injury with the preauricular approach; thus, preservation of the functional integrity of the facial nerve is considered an important factor in the success of temporomandibular joint surgery. The aim of this study was to prevent facial nerve injury using the supratemporalis approach in the treatment of intracapsular condylar fractures. MATERIALS AND METHODS: In this prospective cohort study, the population consisted of patients diagnosed with intracapsular condylar fractures who received surgical treatment from July 2005 to May 2014. Patients in the experimental group were treated with the supratemporalis approach, and patients in the control group were treated with the traditional preauricular surgical technique. The primary outcome variable was facial never injury. The continuity correction chi(2) and test Student t test were used. RESULTS: Eighty-four patients (112 sides) with intracapsular condylar fractures were treated surgically (56 men, 28 women; mean age, 29.85 yr; range, 4 to 70 yr); 44 patients (64 sides) were treated with the supratemporalis approach and 40 patients (48 sides) were treated with the traditional preauricular approach. Facial contours and functions recovered well postoperatively in all 84 patients. Seven cases of facial nerve injury, 2 of which were permanent, were observed in the group treated with the traditional preauricular approach, and no facial nerve injuries were observed in the group treated with the supratemporalis approach. None of the patients sustained auriculotemporal syndrome or wound infection complications. CONCLUSIONS: The supratemporalis approach prevented facial nerve injury and did not increase the frequency of other complications. PMID- 26844403 TI - Selective adsorption of lead on grafted and crosslinked chitosan nanoparticles prepared by using Pb(2+) as template. AB - Poly(acrylic acid) grafted and glutaraldehyde-crosslinked chitosan nano adsorbent (PAACS) was synthesized by using Pb(2+) as a template ion. The structure and morphology of PAACS were characterized by FT-IR, XRD, SEM and elemental analyses. The adsorption of PAACS for different heavy metal ions was compared and the effects of various variables for adsorption of Pb(2+) were systematically studied. The results indicated that the PAACS was the aggregates of nanoparticles with the diameter of about 50-200 nm and had selectivity for Pb(2+) adsorption. The adsorption for Pb(2+) showed a maximum adsorption capacity of 734.3 mg g(-1) at pH 5.0 and 303 K, which was higher than in a study previously reported on ion imprinted adsorbents. The adsorption followed the pseudo-second-order kinetics and Langmuir isotherm models. The adsorption was spontaneous and changed from chemical process into physical process when the temperature exceeded 303 K. The adsorbent could be recycled with EDTA. Therefore, PAACS would be useful as a selective and high uptake nano adsorbent in the removal of Pb(2+) from effluents. PMID- 26844404 TI - Mechanisms of mercury removal by biochars produced from different feedstocks determined using X-ray absorption spectroscopy. AB - Thirty-six biochars produced from distinct feedstocks at different temperatures were evaluated for their potential to remove mercury (Hg) from aqueous solution at environmentally relevant concentrations. Concentrations of total Hg (THg) decreased by >90% in batch systems containing biochars produced at 600 and 700 degrees C and by 40-90% for biochars produced at 300 degrees C. Elevated concentrations of SO4(2-) (up to 1000 mg L(-1)) were observed in solutions mixed with manure-based biochars. Sulfur X-ray absorption near edge structure (XANES) analyses indicate the presence of both reduced and oxidized S species in both unwashed and washed biochars. Sulfur XANES spectra obtained from biochars with adsorbed Hg were similar to those of washed biochars. Micro-X-ray fluorescence mapping results indicate that Hg was heterogeneously distributed across biochar particles. Extended X-ray absorption fine structure modeling indicates Hg was bound to S in biochars with high S content and to O and Cl in biochars with low S content. The predominant mechanisms of Hg removal are likely the formation of chemical bonds between Hg and various functional groups on the biochar. This investigation provides information on the effectiveness and mechanisms of Hg removal that is critical for evaluating biochar applications for stabilization of Hg in surface water, groundwater, soils, and sediments. PMID- 26844405 TI - Estimation of arsenic in agricultural soils using hyperspectral vegetation indices of rice. AB - This study systematically analyzed the performance of multivariate hyperspectral vegetation indices of rice (Oryza sativa L.) in estimating the arsenic content in agricultural soils. Field canopy reflectance spectra was obtained in the jointing booting growth stage of rice. Newly developed and published multivariate vegetation indices were initially calculated to estimate soil arsenic content. The well-performing vegetation indices were then selected using successive projections algorithm (SPA), and the SPA selected vegetation indices were adopted to calibrate a multiple linear regression model for estimating soil arsenic content. Results showed that a three-band vegetation index (R716-R568)/(R552 R568) performed best in the newly developed vegetation indices in estimating soil arsenic content. The photochemical reflectance index (PRI) and red edge position (REP) performed well in the published vegetation indices. Moreover, the linear combination of two vegetation indices ((R716-R568)/(R552-R568) and REP) selected using SPA improved the estimation of soil arsenic content. These results indicated that the newly developed three-band vegetation index (R716-R568)/(R552 R568) might be recommended as an indicator for estimating soil arsenic content in the study area. PRI and REP could be used as universal vegetation indices for monitoring soil arsenic contamination. PMID- 26844406 TI - Effects of particle size and coating on decomposition of alumina-extracted residue from high-alumina fly ash. AB - The effective removal of alkali in the alumina-extracted reside (AER) obtained by extracting alumina from high-alumina fly ash is the premise for realizing the utilization of the silicon component in the fly ash. Sodium was removed from the AER by a decomposition reaction. The effects of the particle size and reactant coating on the decomposition reaction of AER were studied, and the results showed that by decreasing the particle size, the decomposition reaction rate of AER could be enhanced obviously and the Na2O content of the products could be decreased effectively. In addition, the process and mechanism of the decomposition reaction of AER and the reaction kinetics were investigated. The results revealed that the decomposition reaction of AER started from the outer surface of the AER particles. The reaction kinetics corresponded with shrinking unreacted core models. Furthermore, the decomposition reaction rate of AER could be enhanced obviously by decreasing the particle size because the effect of product layer diffusion was weakened when the particle size of AER was decreased. PMID- 26844407 TI - Anaphylaxis to pneumococcal vaccine; CRM(197): Novel cause of vaccine allergy. PMID- 26844408 TI - Validation and utility of the PhysioTelTM Digital M11 telemetry implant for cardiovascular data evaluation in cynomolgus monkeys and Beagle dogs. AB - INTRODUCTION: The cardiovascular liability of candidate compounds can be evaluated by a number of methods including implanted telemetry, jacketed telemetry and surface lead electrocardiogram (ECG). The utility of the new PhysioTelTM Digital M11 cardiovascular telemetry implant was evaluated in monkeys and dogs. METHODS: Eight monkeys and dogs (4 males and 4 females per species) were implanted with the M11 device utilizing a femoral blood pressure catheter and periosteal ECG leads. The signal quality of the ECGs was determined as a percentage of software-matched waveforms and as a percentage of signal loss during the recording periods. To investigate sensitivity for detecting changes in QT/QTc and HR/BP, moxifloxacin and doxazosin were administered to monkeys and dogs implanted with the M11 device. Additionally, histopathological evaluation of the implant site was completed. RESULTS: For both monkey and dog, the percentage of recognizable waveforms was high (65% and 85%, respectively), while the average amount of signal loss was low (1% and 3%, respectively), indicating that the M11 implants delivered data of sufficient quality. In monkeys, moxifloxacin (90mg/kg) induced QT and QTc prolongation up to 22 and 12ms, respectively, while at 30mg/kg in dogs, the maximal increases in QT and QTc were 13 and 16ms, respectively. Doxazosin (1.5 and 1.0mg/kg) produced HR increases up to 35 and 29bpm with decreases in blood pressure up to -14 and -26mmHg in monkeys and dogs, respectively. The histopathological impact of the implant, catheter and biopotential leads was limited to expected minor local inflammatory changes as assessed at necropsy and with microscopic examination. DISCUSSION: Based upon the results of this study, the PhysioTelTM Digital M11 is a suitable technology for assessing cardiovascular parameters in monkeys and dogs, and because of the size and limited invasiveness of the implant, is well positioned for use on toxicology studies. PMID- 26844409 TI - Re: Thyroid Cancer Among Young People in Fukushima. PMID- 26844410 TI - Commentary: Fertility Behavior and Studies of Fecundity Trends. PMID- 26844411 TI - Re: Thyroid Cancer Among Young People in Fukushima. PMID- 26844412 TI - Rejoinder: The Authors Respond. PMID- 26844413 TI - The Authors Respond. PMID- 26844414 TI - Human innate lymphoid cells. AB - The interest in innate lymphoid cells (ILC) has rapidly grown during the last decade. ILC include distinct cell types that are collectively involved in host protection against pathogens and tumor cells and in the regulation of tissue homeostasis. Studies in mice enabled a broad characterization of ILC function and of their developmental requirements. In humans all mature ILC subsets have been characterized and their role in the pathogenesis of certain disease is emerging. Nonetheless, still limited information is available on human ILC development. Indeed, only the cell precursors committed toward NK cells or ILC3 have been described. Here, we review the most recent finding on human mature ILC, discussing their tissue localization and function. Moreover, we summarize the available data regarding human ILC development. PMID- 26844416 TI - Comparative Effectiveness of Conservative Interventions for Nonspecific Chronic Spinal Pain: Physical, Behavioral/Psychologically Informed, or Combined? A Systematic Review and Meta-Analysis. AB - Nonspecific chronic spinal pain (NSCSP) is highly disabling. Current conservative rehabilitation commonly includes physical and behavioral interventions, or a combination of these approaches. Physical interventions aim to enhance physical capacity by using methods such as exercise, manual therapy, and ergonomics. Behavioral/psychologically informed interventions aim to enhance behaviors, cognitions, or mood by using methods such as relaxation and cognitive behavioral therapy. Combined interventions aim to target physical and also behavioral/psychological factors contributing to patients' pain by using methods such as multidisciplinary pain management programs. Because it remains unclear whether any of these approaches are superior, this review aimed to assess the comparative effectiveness of physical, behavioral/psychologically informed, and combined interventions on pain and disability in patients with NSCSP. Ten electronic databases were searched for randomized controlled trials (RCTs) including participants reporting NSCSP. Studies were required to have an "active" conservative treatment control group for comparison. Studies were not eligible if the interventions were from the same domain (eg, if the study compared 2 physical interventions). Study quality was assessed used the Cochrane Back Review Group risk of bias criteria. The treatment effects of physical, behavioral/psychologically informed, and combined interventions were assessed using meta-analyses. Twenty-four studies were included. No clinically significant differences were found for pain and disability between physical, behavioral/psychologically informed, and combined interventions. The simple categorization of interventions into physical, behavioral/psychologically informed, and combined could be considered a limitation of this review, because these interventions may not be easily differentiated to allow accurate comparisons to be made. Further work should consider investigating whether tailoring rehabilitation to individual patients and their perceived risk of chronicity, as seen in recent RCTs for low back pain, can enhance outcomes in NSCSP. PERSPECTIVE: In this systematic review of RCTs in NSCSP, only small differences in pain or disability were observed between physical, behavioral/psychologically informed, and combined interventions. PMID- 26844417 TI - Brain Areas Involved in Anticipation of Clinically Relevant Pain in Low Back Pain Populations With High Levels of Pain Behavior. AB - The purpose of this study was to identify neural correlates of pain anticipation in people with nonspecific low back pain (NSLBP) that correlated with pain related distress and disability, thus providing evidence for mechanisms underlying pain behavior in this population. Thirty NSLBP sufferers, with either high levels of pain behavior or low levels on the basis of Waddell signs, were scanned with functional magnetic resonance imaging while a straight-leg raise (of the side deemed to cause moderate pain in the lower back) was performed. On each trial colored stimuli were presented and used to indicate when the leg definitely would be raised (green; 100% certainty), might be raised (yellow; 50% certainty), or would definitely not be raised (red; 100% certainty). In response to expected versus unexpected pain the group difference in activation between patients with high levels of pain behavior and low levels of pain behavior covaried as a function of anxiety scores in the right insula and pregenual anterior cingulate cortex and as a function of catastrophizing in prefrontal and parietal cortex and hippocampus. The results suggest NSLBP populations with the highest levels of pain-related distress are more likely to attend to and infer threat from innocuous cues, which may contribute to the maintenance of pain behavior associated with some chronic pain states. PERSPECTIVE: This article shows a likely neural network for exacerbating pain anticipation in NSLBP contributing to high levels of pain behavior in some people. This information could potentially help clinicians and patients to understand how anticipation of pain may contribute to patient pain and disability. PMID- 26844418 TI - Histone Acetylation in Microglia Contributes to Exercise-Induced Hypoalgesia in Neuropathic Pain Model Mice. AB - Physical exercise can attenuate neuropathic pain (NPP), but the exact mechanism underlying exercise-induced hypoalgesia (EIH) remains unclear. Recent studies have shown that histone hyperacetylation via pharmacological inhibition of histone deacetylases in the spinal cord attenuates NPP, and that histone acetylation may lead to the production of analgesic factors including interleukin 10. We intended to clarify whether histone acetylation in microglia in the spinal dorsal horn contributes to EIH in NPP model mice. C57BL/6J mice underwent partial sciatic nerve ligation (PSL) and PSL- and sham-runner mice ran on a treadmill at a speed of 7 m/min for 60 min/d, 5 days per week, from 2 days after the surgery. PSL-sedentary mice developed mechanical allodynia and heat hyperalgesia, but such behaviors were significantly attenuated in PSL-runner mice. In immunofluorescence analysis, PSL surgery markedly increased the number of histone deacetylase 1 positive/CD11b-positive microglia in the ipsilateral superficial dorsal horn, and they were significantly decreased by treadmill-running. Moreover, the number of microglia with nuclear expression of acetylated H3K9 in the ipsilateral superficial dorsal horn was maintained at low levels in PSL-sedentary mice, but running exercise significantly increased them. Therefore, we conclude that the epigenetic modification that causes hyperacetylation of H3K9 in activated microglia may play a role in producing EIH. PERSPECTIVE: This article presents the importance of epigenetic modification in microglia in producing EIH. The current research is not only helpful for developing novel nonpharmacological therapy for NPP, but will also enhance our understanding of the mechanisms and availability of exercise in our daily life. PMID- 26844419 TI - High-Definition Transcranial Direct Current Stimulation Enhances Conditioned Pain Modulation in Healthy Volunteers: A Randomized Trial. AB - Transcranial direct current stimulation (tDCS) is a form of brain stimulation that allows for the selective increase or decrease in the cortical excitability of a targeted region. When applied over the motor cortex it has been shown to induce changes in cortical and subcortical brain regions involved in descending pain inhibition or conditioned pain modulation (CPM). The aim of the current study was to assess whether activation of pain inhibitory pathways via tDCS of the motor cortex facilitates the CPM response. Elevated CPM after active tDCS of the motor cortex was hypothesized. Thirty healthy male volunteers attended 2 experimental sessions separated by 7 days. Both sessions consisted of CPM assessment after 20 minutes of either active or sham (placebo) tDCS over the motor cortex. CPM capacity was assessed via the pain-inhibits-pain protocol; CPM responses were shown to be elevated after active compared with sham tDCS. This report concludes that tDCS of the motor cortex enhances the CPM response in healthy men. This finding supports the potential utility of tDCS interventions in clinical pain treatment. PERSPECTIVE: The use of noninvasive brain stimulation over the motor cortex was shown to enhance the CPM effect. This finding supports the use of tDCS in the treatment of chronic pain, particularly in sufferers exhibiting maladaptive CPM. PMID- 26844415 TI - Fatty Acids and Breast Cancer: Make Them on Site or Have Them Delivered. AB - Brisk fatty acid (FA) production by cancer cells is accommodated by the Warburg effect. Most breast and other cancer cell types are addicted to fatty acids (FA), which they require for membrane phospholipid synthesis, signaling purposes, and energy production. Expression of the enzymes required for FA synthesis is closely linked to each of the major classes of signaling molecules that stimulate BC cell proliferation. This review focuses on the regulation of FA synthesis in BC cells, and the impact of FA, or the lack thereof, on the tumor cell phenotype. Given growing awareness of the impact of dietary fat and obesity on BC biology, we will also examine the less-frequently considered notion that, in addition to de novo FA synthesis, the lipolytic uptake of preformed FA may also be an important mechanism of lipid acquisition. Indeed, it appears that cancer cells may exist at different points along a "lipogenic-lipolytic axis," and FA uptake could thwart attempts to exploit the strict requirement for FA focused solely on inhibition of de novo FA synthesis. Strategies for clinically targeting FA metabolism will be discussed, and the current status of the medicinal chemistry in this area will be assessed. J. Cell. Physiol. 231: 2128-2141, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26844420 TI - Associations among environmental exposure to manganese, neuropsychological performance, oxidative damage and kidney biomarkers in children. AB - Environmental exposure to manganese (Mn) results in several toxic effects, mainly neurotoxicity. This study investigated associations among Mn exposure, neuropsychological performance, biomarkers of oxidative damage and early kidney dysfunction in children aged 6-12 years old. Sixty-three children were enrolled in this study, being 43 from a rural area and 20 from an urban area. Manganese was quantified in blood (B-Mn), hair (H-Mn) and drinking water using inductively coupled plasma mass spectrometry (ICP-MS). The neuropsychological functions assessed were attention, perception, working memory, phonological awareness and executive functions - inhibition. The Intelligence quotient (IQ) was also evaluated. The biomarkers malondialdehyde (MDA), protein carbonyls (PCO), delta aminolevulinate dehydratase (ALA-D), reactivation indexes with dithiothreitol (ALA-RE/DTT) and ZnCl2 (ALA-RE/ZnCl2), non-protein thiol groups, as well as microalbuminuria (mALB) level and N-acetyl-beta-D-glucosaminidase (NAG) activity were assessed. The results demonstrated that Mn levels in blood, hair and drinking water were higher in rural children than in urban children (p<0.01). Adjusted for potential confounding factors, IQ, age, gender and parents' education, significant associations were observed mainly between B-Mn and visual attention (beta=0.649; p<0.001). Moreover, B-Mn was negatively associated with visual perception and phonological awareness. H-Mn was inversely associated with working memory, and Mn levels from drinking water with written language and executive functions - inhibition. Rural children showed a significant increase in oxidative damage to proteins and lipids, as well as alteration in kidney function biomarkers (p<0.05). Moreover, significant associations were found between B-Mn, H-Mn and Mn levels in drinking water and biomarkers of oxidative damage and kidney function, besides between some oxidative stress biomarkers and neuropsychological tasks (p<0.05). The findings of this study suggest an important association between environmental exposure to Mn and toxic effects on neuropsychological function, oxidative damage and kidney function in children. PMID- 26844421 TI - Synthesis of Natural and Unnatural Cyclooligomeric Depsipeptides Enabled by Flow Chemistry. AB - Flow chemistry has been successfully integrated into the synthesis of a series of cyclooligomeric depsipeptides of three different ring sizes including the natural products beauvericin (1 a), bassianolide (2 b) and enniatin C (1 b). A reliable flow chemistry protocol was established for the coupling and macrocyclisation to form challenging N-methylated amides. This flexible approach has allowed the rapid synthesis of both natural and unnatural depsipeptides in high yields, enabling further exploration of their promising biological activity. PMID- 26844422 TI - Detection of C-reactive protein using nanoparticle-enhanced surface plasmon resonance using an aptamer-antibody sandwich assay. AB - High affinity DNA aptamers against C-reactive protein (CRP) were obtained using a microfluidic chip. The aptamers were then used for the construction of an Au nanoparticle enhanced surface plasmon resonance biosensor, which was introduced for the detection of CRP at concentrations ranging from 10 pM to 100 nM in diluted human serum. PMID- 26844423 TI - Undetected Dural Leaks Complicated by Accidental Drainage of Cerebrospinal Fluid (CSF) can Lead to Severe Neurological Deficits. AB - PURPOSE: Intracranial hypotension has been reported as a complication of accidental drainage after surgical treatment in several cases. Application of negative pressure systems (wound drains, VAC((r))-therapy, chest tube drainage) had typically led to severe intracranial hypotension including intracranial hemorrhage and tonsillar herniation. In the last year the authors observed 2 cases of accidental spinal drainage of CSF in patients with neurological deficits, regressing after reduction of the device suction. MATERIAL AND METHODS: We conducted a systematic PubMed-based research of the literature to study the variety and frequency of the reported symptoms from 1st of January 1980 until 1st of October 2015. RESULTS: Reviewing the literature 24 relevant citations including 27 reported cases of posttraumatic or postoperative loss of CSF leading to neurological symptoms were identified. All 15 reported cases in which a negative pressure suction device had been applied showed severe neurological and radiological symptoms such as coma or brain herniation and intracranial hemorrhage. In all cases patients recovered rapidly after removal of the suction device. Milder symptoms were observed in the patients without negative pressure suction, mainly only presenting with headaches or cranial nerve involvement.Additionally, we give an overview about current recommendations regarding cranial and spinal imaging to rule out dural laceration and cranial hypotension. CONCLUSION: Patients with dural laceration complicated by accidental drainage of CSF can present with life-threatening conditions. Increasing use of negative pressure suction devices makes the reported condition an important differential diagnosis. A precise radiological examination can help to rule out dural laceration and intracranial hypotension. KEY POINTS: * Undetected dural laceration complicated by negative pressure suction drains can induce life threatening symptoms.* Increasing use of negative pressure suction devices makes the reported condition an important differential diagnosis for radiologists Citation Format: * Sporns PB, Schwindt W, Cnyrim CD et al. Undetected Dural Leaks Complicated by Accidental Drainage of Cerebrospinal Fluid (CSF) can Lead to Severe Neurological Deficits. Fortschr Rontgenstr 2016; 188: 451 - 458. PMID- 26844424 TI - Concise Review: Cell Therapies for Stroke and Traumatic Brain Injury: Targeting Microglia. AB - We present a model hypothesis of how several types of cell therapies may target microglia as one of the principal cell types contributing to the inflammatory response after brain injury and discuss how imaging of brain inflammation could potentially be applied to develop biomarkers in patients with stroke and TBI enrolled into stem cell clinical trials. PMID- 26844427 TI - Bridging the gap: Using Veerman and Van Yperen's (2007) framework to conceptualise and develop evidence informed practice in an Irish youth work organisation. AB - While there is considerable support among the policy, practice and academic communities for the idea that practice in youth work should be based on evidence, Veerman and Van Yperen (2007) highlight the fact that little practice in the area of youth care is actually evidence based due to the paucity of experimental studies in the field and the difficulties associated with evaluation of non standardised interventions such as youth work. They propose a model consisting of levels of evidence, the aim of which is to 'bridge the gap between evidence based and evidence informed practice' (p. 218). In order to address the dearth of examples in the international literature of how organisations have dealt with these complexities in practice, this article provides a case study of how a large Irish youth organisation, Foroige, has endeavoured to adopt an inclusive approach to evidence, working towards both evidence based and evidence informed practice. Drawing on Veerman and Van Yperen's (2007) framework, the case study shows that Foroige committed itself to gathering different types of evidence, including logic models and theoretical understandings at the foundation level and experimental design studies of key programmes at the advanced level. The case study focuses in detail on the intermediate level, whereby practitioners were trained to evaluate aspects of their own work, with a view to embedding evaluation and reflection in day to day practice. The process is described and key lessons emerging are discussed. PMID- 26844425 TI - B Cell-Activating Transcription Factor Plays a Critical Role in the Pathogenesis of Anti-Major Histocompatibility Complex-Induced Obliterative Airway Disease. AB - Antibodies (Abs) against major histocompatibility complex (MHC) results in T helper-17 (Th17)-mediated immunity against lung self-antigens (SAgs), K-alpha1 tubulin and collagen V and obliterative airway disease (OAD). Because B cell activating transcription factor (BATF) controls Th17 and autoimmunity, we proposed that BATF may play a critical role in OAD. Anti-H2K(b) was administered intrabronchially into Batf (-/-) and C57BL/6 mice. Histopathology of the lungs on days 30 and 45 after Ab administration to Batf (-/-) mice resulted in decreased cellular infiltration, epithelial metaplasia, fibrosis, and obstruction. There was lack of Abs to SAgs, reduction of Sag-specific interleukin (IL)-17 T cells, IL-6, IL-23, IL-17, IL-1beta, fibroblast growth factor-6, and CXCL12 and decreased Janus kinase 2, signal transducer and activator of transcription 3 (STAT3), and retinoid-related orphan receptor gammaT. Further, micro-RNA (miR) 301a, a regulator of Th17, was reduced in Batf (-/-) mice in contrast to upregulation of miR-301a and downregulation of protein inhibitor of activated STAT3 (PIAS3) in anti-MHC-induced OAD animals. We also demonstrate an increase in miR-301a in the bronchoalveolar lavage cells from lung transplant recipients with Abs to human leukocyte antigen. This was accompanied by reduction in PIAS3 mRNA. Therefore, we conclude that BATF plays a critical role in the immune responses to SAgs and pathogenesis of anti-MHC-induced rejection. Targeting BATF should be considered for preventing chronic rejection after human lung transplantation. PMID- 26844426 TI - Extracellular matrix mediators of metastatic cell colonization characterized using scaffold mimics of the pre-metastatic niche. AB - Metastatic tumor cells colonize the pre-metastatic niche, which is a complex microenvironment consisting partially of extracellular matrix (ECM) proteins. We sought to identify and validate novel contributors to tumor cell colonization using ECM-coated poly(epsilon-caprolactone) (PCL) scaffolds as mimics of the pre metastatic niche. Utilizing orthotopic breast cancer mouse models, fibronectin and collagen IV-coated scaffolds implanted in the subcutaneous space captured colonizing tumor cells, showing a greater than 2-fold increase in tumor cell accumulation at the implant site compared to uncoated scaffolds. As a strategy to identify additional ECM colonization contributors, decellularized matrix (DCM) from lungs and livers containing metastatic tumors were characterized. In vitro, metastatic cell adhesion was increased on DCM coatings from diseased organs relative to healthy DCM. Furthermore, in vivo implantations of diseased DCM coated scaffolds had increased tumor cell colonization relative to healthy DCM coatings. Mass-spectrometry proteomics was performed on healthy and diseased DCM to identify candidates associated with colonization. Myeloperoxidase was identified as abundantly present in diseased organs and validated as a contributor to colonization using myeloperoxidase-coated scaffold implants. This work identified novel ECM proteins associated with colonization using decellularization and proteomics techniques and validated candidates using a scaffold to mimic the pre-metastatic niche. STATEMENT OF SIGNIFICANCE: The pre metastatic niche consists partially of ECM proteins that promote metastatic cell colonization to a target organ. We present a biomaterials-based approach to mimic this niche and identify ECM mediators of colonization. Using murine breast cancer models, we implanted microporous PCL scaffolds to recruit colonizing tumor cells in vivo. As a strategy to modulate colonization, we coated scaffolds with various ECM proteins, including decellularized lung and liver matrix from tumor-bearing mice. After characterizing the organ matrices using proteomics, myeloperoxidase was identified as an ECM protein contributing to colonization and validated using our scaffold. Our scaffold provides a platform to identify novel contributors to colonization and allows for the capture of colonizing tumor cells for a variety of downstream clinical applications. PMID- 26844428 TI - Targeted in vivo genetic manipulation of the mouse or rat brain by in utero electroporation with a triple-electrode probe. AB - This protocol is an extension to:Nat. Protoc. 1, 1552-1558 (2006); doi:10.1038/nprot.2006.276; published online 9 November 2006This article describes how to reliably electroporate with DNA plasmids rodent neuronal progenitors of the hippocampus; the motor, prefrontal and visual cortices; and the cerebellum in utero. As a Protocol Extension article, this article describes an adaptation of an existing Protocol and offers additional applications. The earlier protocol describes how to electroporate mouse embryos using two standard forceps-type electrodes. In the present protocol, additional electroporation configurations are possible because of the addition of a third electrode alongside the two standard forceps-type electrodes. By adjusting the position and polarity of the three electrodes, the electric field can be directed with great accuracy to different neurogenic areas. Bilateral transfection of brain hemispheres can be achieved after a single electroporation episode. Approximately 75% of electroporated embryos survive to postnatal ages, and depending on the target area, 50-90% express the electroporated vector. The electroporation procedure takes 1 h 35 min. The protocol is suitable for the preparation of animals for various applications, including histochemistry, behavioral studies, electrophysiology and in vivo imaging. PMID- 26844429 TI - Mammalian NET-seq analysis defines nascent RNA profiles and associated RNA processing genome-wide. AB - The transcription cycle of RNA polymerase II (Pol II) correlates with changes to the phosphorylation state of its large subunit C-terminal domain (CTD). We recently developed Native Elongation Transcript sequencing using mammalian cells (mNET-seq), which generates single-nucleotide-resolution genome-wide profiles of nascent RNA and co-transcriptional RNA processing that are associated with different CTD phosphorylation states. Here we provide a detailed protocol for mNET-seq. First, Pol II elongation complexes are isolated with specific phospho CTD antibodies from chromatin solubilized by micrococcal nuclease digestion. Next, RNA derived from within the Pol II complex is size fractionated and Illumina sequenced. Using mNET-seq, we have previously shown that Pol II pauses at both ends of protein-coding genes but with different CTD phosphorylation patterns, and we have also detected phosphorylation at serine 5 (Ser5-P) CTD specific splicing intermediates and Pol II accumulation over co-transcriptionally spliced exons. With moderate biochemical and bioinformatic skills, mNET-seq can be completed in ~6 d, not including sequencing and data analysis. PMID- 26844431 TI - Diagnostic performance of [18F] FDG PET-CT compared to bone scintigraphy for the detection of bone metastases in lung cancer patients. AB - BACKGROUND: Accurate staging of lung cancer is essential for effective patient management and selection of appropriate therapeutic strategy. The aim of this paper was to compare the value of bone scintigraphy and FDG PET-CT for detecting bone metastases in lung cancer patients and the impact of these modalities in disease staging. METHODS: One hundred sixty-four lung cancer patients who had undergone both FDG PET-CT and bone scintigraphy within 14 days were included into this study. The analysis of FDG PET-CT and bone scintigraphy was carried out patient- and lesion-based. RESULTS: One hundred twenty-one patients were negative and 43 patients positive for bone metastases. FDG PET-CT found bone metastases in 42/43 patients and bone scintigraphy in 38/43 patients. Sensitivity, specificity and accuracy of FDG PET-CT and bone scintigraphy for detecting bone metastases were 97.7%, 100% and 99.4%, and 87.8%, 97.5% and 94.2%, respectively. FDG PET-CT identified 430 bone metastases and bone scintigraphy 246 bone metastases. Skull was the only region where bone scintigraphy identified more lesions than FDG PET CT. Based on both scintigraphic modalities disagreement concerning disease stage was found in 3 patients. CONCLUSION: FDG PET-CT yielded a higher sensitivity, specificity and accuracy than bone scintigraphy for identifying bone metastases in lung cancer patients. FDG PET-CT thus can be recommended for initial staging of lung cancer patients without applying bone scintigraphy for the detection of bone metastases. PMID- 26844432 TI - [Nanotechnology and nanomedicine: advances and promises for human health]. PMID- 26844430 TI - Ultra-high-throughput sequencing of the immune receptor repertoire from millions of lymphocytes. AB - High-throughput sequencing of the variable domains of immune receptors (antibodies and T cell receptors (TCRs)) is of key importance in the understanding of adaptive immune responses in health and disease. However, the sequencing of both immune receptor chains (VH+VL or TCRbeta/delta+TCRalpha/gamma) at the single-cell level for typical samples containing >10(4) lymphocytes is problematic, because immune receptors comprise two polypeptide chains that are encoded by separate mRNAs. Here we present a technology that allows rapid and low cost determination of a paired immune receptor repertoire from millions of cells with high precision (>97%). Flow focusing is used to encapsulate single cells in emulsions containing magnetic beads for mRNA capture. The mRNA transcripts are then reverse-transcribed, physically linked to their partners by overlap extension PCR, and interrogated by high-throughput paired-end Illumina sequencing. This protocol describes the construction and operation of the flow focusing device in detail, as well as the bioinformatics pipeline used to interpret the data. The entire procedure can be performed by a single researcher in under 12 h of effort per sample. PMID- 26844434 TI - [Cutaneous gnathostomiasis, first confirmed case in Colombia]. AB - Gnathostomiasis is a parasitic zoonosis caused by some species of helminthes belonging to the genus Gnathostoma . It has a wide clinical presentation and its diagnosis is a challenge. Tropical and subtropical countries are endemic, and its transmission is associated with eating raw or undercooked meat from fresh water animals. Increasing global tourism and consuming exotic foods have produced a noticeable rise in cases of the disease in the last decades. However, in our country, there has not been any confirmed case of gnathostomiasis previously reported. We present the case of a 63-year-old Colombian man with an international travel history, who presented with gastrointestinal symptoms. During the hospital stay, he developed a cutaneous lesion on the upper right abdominal quadrant, where later, a larva was found. A morphological study allowed us to identify it as Gnathostoma spinigerum . As such, this is the first report of an imported case of gnathostomiasis confirmed in Colombia. This article describes the principles, etiology, pathogenic cycle and treatment of this disease with special considerations to our patient's particular features. PMID- 26844433 TI - [Pott's disease in a Colombian indigenous man]. AB - Approximately 2 million people die each year from tuberculosis. One third of the world's population is estimated to be infected with the tuberculosis bacillus, although only 5-10% will develop the disease in their lifetime. The disease progression risk depends on endogenous and exogenous factors. Indigenous communities are a high-risk group for infection and development of tuberculosis. In addition to factors such as geographical isolation, social and cultural neglect and malnutrition, susceptibility to genetic polymorphisms has been identified in them. Spinal tuberculosis is the most destructive form of the disease, which represents approximately half of all cases of skeletal tuberculosis. The case of an HIV negative, indigenous Colombian man is presented. His diagnosis was done based on clinical and image findings, and it was confirmed with the rapid molecular assay Genotype MTBDRplus(r) and IS6110 PCR.The culture in solid media was negative after 16 weeks. We briefly discuss the pathogenesis, diagnosis and treatment. Finally, we comment on some aspects of the situation of tuberculosis among indigenous Colombian communities. PMID- 26844435 TI - [Osteomyelitis due to Yokenella regensburgei following craniotomy in an immunocompetent patient]. AB - The gram-negative bacillus Yokenella regensburgei (of the Enterobacteriaceae family) can be found in groundwater and foodstuffs, as well as the digestive tracts of insects and reptiles. Although it has been isolated from humans since its original description, it has rarely been reported as a cause of infection, and then, only in immunosuppressed patients. We report the first case of post surgical secondary osteomyelitis due to Y. regensburgei in an immunocompetent woman who had undergone a craniotomy. PMID- 26844436 TI - [Symptoms of myasthenia gravis in a patient with a history of thymectomy for invasive thymoma]. AB - INTRODUCTION: Myasthenia gravis is an antibody-mediated autoimmune disease. Approximately 10-15% of patients present with a thymoma, the presence of which is associated with greater severity of symptoms, myasthenic crisis, and irresponsiveness to front-line therapy. A thymectomy is recommended in young patients with generalized myasthenia gravis and in all patients presenting with thymoma. CLINICAL CASE: The patient was a 43-year-old woman, who first showed symptoms of myasthenic crisis in 2005 and presented with invasive thymoma managed with thymectomy and radiotherapy. In the subsequent three years, the patient presented with severe symptoms and two myasthenic crises that required mechanical ventilation and immunoglobulin treatment. Contrast chest computed tomography examinations showed no recurrence. Between 2009 and 2012, the patient experienced decreased symptom severity. In 2013, the patient presented with an exacerbation of symptoms; a contrast chest magnetic resonance scan showed a lesion in the anterior mediastinum, previously observed in 2011, suggestive of residual tissue as opposed to fibrosis. Regular management was started with immunoglobulins; a positron emission tomography scan was inconclusive, requiring a new resection, which showed no evidence of tumor recurrence. CONCLUSIONS: Patients with myasthenia gravis and those with myasthenia-related thymoma both share thymectomy as an element of treatment. However, following the procedure, exacerbation or reappearance of symptoms does not necessarily represent new alterations in the thymus. PMID- 26844437 TI - [Knowledge, attitudes and practices regarding malaria in the indigenous Guna population of the Madungandi region, Panama, 2012]. AB - INTRODUCTION: Knowledge, attitudes and practices surveys allow to determine the degree of knowledge on the management of malaria in a given population, as well as the attitudes and practices that contribute or not to its transmission. OBJECTIVE: To identify the knowledge, attitudes and practices that favor or not the transmission of malaria in the indigenous Guna population of Madungandi. MATERIALS AND METHODS: A cross-sectional study was conducted by applying a survey to the heads of the families in a sample of 40% of households in three communities with high malaria incidence. Local Guna residents and translators were part of the research team that applied the questionnaires. The statistical analysis was performed in Epi-Info 6.04. RESULTS: The age range of those surveyed was between 20 and 70 years. All responders indicated that they belonged to and spoke the language of the Guna ethnic group, 64% were male and 30% were illiterate. Half (51%) of the responders declared they had suffered malaria at least once in the last eight years, and 89% accepted that malaria was a health problem. Sixty-three per cent responded that their traditional doctors, ?inadule?, cured malaria and 7.0 % practiced the ?pipe smoking? and ?cocoa burn? rituals to prevent the disease. CONCLUSION: Considering the limited knowledge about malaria and its vector, as well as the willingness to collaborate shown by the Guna population, it is essential to initiate educational and participative programs to improve control and prevention activities in the communities aimed at achieving a reduction in malaria incidence in the Madungandi indigenous region. PMID- 26844438 TI - [Molecular characterization of an outbreak of carbapenem-resistant Klebsiella pneumoniae in a tertiary care hospital in Medellin, Colombia]. AB - INTRODUCTION: Resistance to carbapenems is considered to represent a serious threat to public health at the global level, since these antibiotics are one of the last therapeutic options for the treatment of multidrug-resistant bacteria. Molecular characterization of outbreaks due to resistant bacteria provides information that can be used in the design of infection control strategies. OBJECTIVE: To describe the molecular characteristics of an outbreak of carbapenem resistant Klebsiella pneumoniae that occurred in a tertiary care hospital in Medellin in 2010-2011. MATERIALS AND METHODS: Eighty-four isolates were obtained from a collection of strains associated with the hospital outbreak, of which 32 were from patients infected at that time and 52 were carriers. Identification and susceptibility of the isolates was performed using Vitek2(r). Carbapenemases were detected using a modified Hodge test and polymerase chain reaction. Genetic relationships between the isolates were evaluated using pulsed field gel electrophoresis and multiple locus sequence typing. RESULTS: All the isolates analyzed were multidrug resistant; molecular analysis revealed that all harbored bla KPC-3 . The genetic analysis showed that 58/64 of the isolates from both infected and colonized patients were closely related (Dice similarity index >80%) and belonged to the ST258 lineage. CONCLUSION: Using molecular typing techniques it was possible to confirm the occurrence of an outbreak caused by K. pneumoniae ST258, a carrier of bla KPC-3 with a multidrug-resistant profile which had been associated with a previous outbreak in another hospital in the city of Medellin. ST258 is a high risk clone at the global level, demonstrating the potential for dissemination of resistance in this country. Implementation of molecular tools in support of epidemiological surveillance is useful for evaluating the spread of microorganisms of public health significance. PMID- 26844439 TI - [Factors associated with the timely treatment of women with breast cancer supported by a non-governmental organization in Bogota, Colombia]. AB - INTRODUCTION: The prognosis for a woman with breast cancer is related to the time that elapses before diagnosis and integral treatment. Colombian women face barriers that determine effective access to the health system. OBJECTIVE: To establish the determinants of timely treatment for breast cancer in a group of women supported by a non-governmental organization in Bogota. MATERIALS AND METHODS: An observational analytical study was carried out on 136 women with breast cancer supported by the non-governmental organization. The cut-off point for timely treatment was defined as 90 days, calculated as the time between the appearance of symptoms and the initiation of treatment. Predictors of timely treatment were explored by means of multivariate analysis. RESULTS: Although 96% of the women had health insurance only 26.4% received timely treatment, and 36 of them reported being denied medical services. Of these women, 23% took legal action to gain access to their healthcare rights. Significant associations were established by multivariate analysis for timely treatment among women belonging to socioeconomic strata IV and V (OR=3.39), as well as those with higher education (OR=2.72). CONCLUSIONS: According to the international literature, the prognosis for women with breast cancer improves when they are able to access opportune treatment. In this group of women socioeconomic factors appeared to determine effective access to treatment, revealing the existence of inequalities that may be socially determined. PMID- 26844440 TI - [Impact of the flipped classroom strategy in the learning environment in surgery: A comparison with the lectures]. AB - INTRODUCTION: The Facultad de Medicina of the Universidad de La Sabana routinely uses lectures as the major educational strategy in clinical areas. Since 2012, a curriculum in context and a flipped classroom were introduced in the surgery course. OBJECTIVE: To compare the impact of lectures versus the flipped classroom model in the learning environment in surgery. MATERIALS AND METHODS: The Dundee Ready Education Environment Measure (DREEM) questionnaire was administered to four cohorts of students. The five domains and the overall scores for both strategies were analyzed, and ANOVA was used to determine the differences among the domains (p<0.05). The internal consistency was assessed using Cronbach's alpha coefficient. RESULTS: There were 207 participants (men: 36%) that completed the questionnaire (age: 21.9 +/- 1.49 years old). The overall DREEM score and the subscales were higher with the flipped classroom, which suggests that this environment had a higher level of excellence. The ANOVA for each domain and the overall scores showed no differences with a flipped classroom. However, significant differences were identified in all domains and the overall scores with lectures (p<0.01). There were high levels of reliability (Cronbach>0.90) for all measurements in both environments, and there was consistency across all cohorts. CONCLUSIONS: The flipped classroom strategy showed a higher score than the lecture-based approach according to the DREEM questionnaire. Identifying factors with a negative score is crucial to improving the learning environment. It is necessary to conduct further measurements over time to ensure the quality and success of the strategy. PMID- 26844441 TI - [Carbapenem-resistant Acinetobacter baumannii causing osteomyelitis and infections of skin and soft tissues in hospitals of Medellin, Colombia]. AB - INTRODUCTION: Acinetobacter baumannii is an opportunistic bacterium which infects seriously ill patients, particularly those with ventilator-associated pneumonia and bacteremia. The emergence of resistance to carbapenem limits the options for the treatment of infections caused by this bacterium. OBJECTIVE: To describe the clinical and molecular characteristics of infections caused by carbapenem resistant A. baumannii in Medellin hospitals. MATERIALS AND METHODS: A cross sectional descriptive study was carried out in five Medellin hospitals over a 2 year period. Clinical information was obtained from medical histories of patients. The presence of carbapenemases was evaluated by three-dimensional test and PCR. Molecular typing was performed using PFGE and MLST. RESULTS: The study included 32 patients, 13 of whom presented skin and soft tissue infections (n=7, 21.9%) or osteomyelitis (n=6, 18.7%). Resistance rates of the isolates exceeded 80% for all the antibiotics evaluated except colistin and tigecycline. Carbapenemases OXA-23 and OXA-51, as well as the insertion sequence IS Aba1 , were detected in all the isolates. PFGE revealed high genetic diversity in the isolates and MLST showed clones ST229 and ST758 are circulating in the city. CONCLUSION: In contrast to previous reports, the results of the present study showed osteomyelitis and infections of skin and soft tissues to be the main infections caused by carbapenem-resistant A. baumannii in Medellin hospitals and revealed its importance as an etiological agent for this type of infections. PMID- 26844442 TI - Cost-effectiveness analysis of ticagrelor compared to clopidogrel for the treatment of patients with acute coronary syndrome in Colombia. AB - INTRODUCTION: Acute coronary syndrome is one of the most frequent medical emergencies in developing countries. OBJECTIVE: To determine, from the perspective of the Colombian health system, the cost-effectiveness of ticagrelor compared to clopidogrel for the treatment of patients with acute coronary syndrome. MATERIALS AND METHODS: We conducted a cost-effectiveness analysis from the perspective of the Colombian health system comparing ticagrelor and clopidogrel for the treatment of patients with acute coronary syndrome. To estimate the expected costs and outcomes, a Markov model was constructed in which patients could remain stable without experiencing new cardiovascular events, suffer from a new event, or die. For the baseline case, a 10-year time horizon and a discount ratio of 3% for costs and benefits were adopted. The transition probabilities were extracted from the PLATO (Platelet Inhibition and Patient Outcomes) clinical trial. Vital statistics were drawn from the Departmento Administrativo Nacional de Estadistica (DANE) and additional information from Colombian patients included in the Access registry. To identify and measure resource use, a standard case was built by consulting guidelines and protocols. Unit costs were obtained from Colombian rate lists. A probabilistic sensitivity analysis was conducted in which costs were represented by a triangular distribution, and the effectiveness through a beta distribution. RESULTS: In the base case, the additional cost per quality-adjusted life-year gained with ticagrelor was COP$ 28,411,503. The results were sensitive to changes in the time horizon and the unit cost of clopidogrel. For a willingness-to-pay equivalent to three times the Colombian per capita gross domestic product, the probability of ticagrelor being cost-effective was 75%. CONCLUSIONS: Ticagrelor is a cost effective strategy for the treatment of patients with acute coronary syndrome in Colombia. PMID- 26844443 TI - [GenoType MTBDR plus 1.0(r) for the detection of cross-resistance between isoniazide and ethionamide in isolates of multidrug-resistant Mycobacterium tuberculosis]. AB - INTRODUCTION: A variable proportion of isolates of multidrug-resistant Mycobacterium tuberculosis also presents resistance to ethionamide. It is important to determine whether resistance to isoniazid is independent or crossed with resistance to ethionamide, given that this could lead to the re-evaluation of second-line anti-tuberculosis treatment. The GenoType MTBDR plus (r) molecular test is used for the detection of MDR-MTB, as it identifies mutations associated with resistance to isoniazide and could detect cross-resistance with ethionamide. OBJECTIVE: To evaluate the performance of GenoType MTBDR plus (r) in comparison with sequencing in the detection of mutations in gene katG and promotor inhA in clinical isolates of multidrug-resistant M. tuberculosis . MATERIALS AND METHODS: The GenoType MTBDR plus 1.0(r) commercial kit and sequencing were used to evaluate mutations in gene katG and promotor inhA in 30 multidrug-resistant M. tuberculosis isolates that were resistant to ethionamide. The laboratory strain H37Rv and three pan-sensitive isolates acted as controls. RESULTS: The kappa index for the comparison between the results of sequencing and GenoType MTBDR plus(r) was 1. All the isolates resistant to isoniazid and ethionamide had the mutations detected by GenoTypeMTBDR plus(r) in the katG gene and 40% of them in promotor inhA. Sequencing also revealed katG mutations in positions different to those detected by GenoType MTBDR plus(r). CONCLUSION: GenoType MTBDR plus (r) is able to detect resistance to isoniazid rapidly. Our results suggest that it could also be used to screen for cross-resistance with ethionamide. PMID- 26844444 TI - [Cost-effectiveness of consolidation treatments for acute myeloid leukemia in high-risk pediatric patients within the Colombian healthcare system]. AB - INTRODUCTION: Acute myeloid leukemia represents about 20% of leukemias in minors under 18 years old. At present, there are only two consolidation treatment alternatives: Chemotherapy and stem-cell transplantation. OBJECTIVE: To evaluate the cost-effectiveness of unrelated and related hematopoietic stem cell transplantations, versus chemotherapy consolidation in pediatric patients with high-risk acute myeloid leukemia. MATERIALS AND METHODS: A decision tree was constructed with life-years gained as the outcome. Costs and probabilities were extracted from the literature. Probabilistic sensitivity analyses and acceptability curves were computed. The cost-effectiveness threshold was three times the 2010 per capita gross domestic product. RESULTS: When compared to consolidation chemotherapy cycles, related and unrelated hematopoietic stem-cell transplantation had incremental cost-effectiveness ratios of COP$ 9,226,421 (USD$ 4,820) and COP$ 6,544,116 (USD$ 3,419) respectively, which are lower than the per capita gross domestic product (COP$ 12,047,418, USD$ 6,294). Transplant proved to be cost-effective in 70% of the simulations and had a higher probability of the willingness to pay being over than COP$ 7,200,000 (USD$ 3,762). CONCLUSION: In Colombia, related and unrelated hematopoietic stem-cell transplants are cost effective alternatives to consolidation treatment for high-risk acute myeloid leukemia in pediatric patients. PMID- 26844445 TI - Serological evidence of leptospirosis in patients with a clinical suspicion of dengue in the State of Ceara, Brazil. AB - INTRODUCTION: Dengue and leptospirosis are two febrile illnesses of great clinical and epidemiological importance in Brazil. Their significant degree of symptomatic similarity makes clinical diagnosis difficult. OBJECTIVE: To diagnose leptospirosis differentially in patients with clinically suspected dengue. MATERIALS AND METHODS: In this study, 86 patients with clinically suspected dengue underwent virological and serological diagnostic evaluations for dengue (reverse transcriptase polymerase chain reaction, NS1 immunochromatographic test, and NS1 enzyme-linked immunosorbent assay, ELISA), as well as tests to detect immunoglobulin M (IgM; IgM/IgG Rapid Test and IgM ELISA). The same patients were subsequently evaluated for leptospirosis using Rapid Test IgG/IgM (Bioeasy(r)) and Leptospira IgM ELISA (PanBio(r)). RESULTS: Of the 86 patients, 48 (55.8%) had positive results for dengue in at least one of the tests and five (7.35%) showed positive reactions for leptospirosis. CONCLUSION: During dengue epidemics, this disease may be misdiagnosed as other infections, including leptospirosis, when diagnosis is based on nonspecific clinical and laboratory criteria alone. PMID- 26844446 TI - Novel cerebrotendinous xanthomatosis mutation causes familial early dementia in Colombia. AB - INTRODUCTION: Cerebrotendinous xanthomatosis is an infrequent cause of dementia. It is an autosomal recessive disorder with clinical and molecular heterogeneity. OBJECTIVE: To identify the presence of a possible mutation in a Colombian family with several affected siblings and clinical characteristics compatible with cerebrotendinous xanthomatosis associated to early dementia. MATERIALS AND METHODS: We studied a series of cases with longitudinal follow-up and genetic analysis. RESULTS: These individuals had xanthomas, mental retardation, psychiatric disorders, behavioral changes, and multiple domains cognitive impairment with dysexecutive dominance that progressed to early dementia. CYP27A1 gene coding region sequencing revealed a novel mutation (c.1183_1184insT). CONCLUSION: The mutation found in this family is responsible for the described dementia features. Early identification of familial history with mental retardation, xanthomas and cognitive impairment might prevent the progression to this treatable type of dementia. Even though this mutation lies in the most frequently mutated codon of CYP27A1 gene, it has not been reported previously. PMID- 26844447 TI - Aedes aegypti anti-salivary gland antibody concentration and dengue virus exposure history in healthy individuals living in an endemic area in Colombia. AB - INTRODUCTION: Mosquito salivary proteins are able to induce an antibody response that reflects the level of human-vector contact. IgG antibodies against dengue virus (DENV-IgG) are indicators of previous exposure. The risk of DENV transmission is not only associated to mosquito or dengue factors, but also to socioeconomic factors that may play an important role in the disease epidemiology. OBJECTIVE: To determine the effect of the presence of Aedes aegypti mosquitos in different stages in households and the history of dengue exposure on vector-human contact determined by the level of anti-salivary protein antibodies in people living in a Colombian endemic area. MATERIALS AND METHODS: A pilot study of 58 households and 55 human subjects was conducted in Norte de Santander, Colombia. A questionnaire for socioeconomic factors was administered and houses were examined for the presence of Ae. aegypti specimens in the aquatic stages. The level of DENV-IgG antibodies (DENV-IgG), in addition to IgG and IgM anti- Ae. aegypti salivary gland extract (SGE) antibodies (SGE-IgG, SGE-IgM) were evaluated by ELISA using blood collected in filter paper. RESULTS: We found a significant higher level of SGE-IgG antibodies in subjects living in houses with Ae. aegypti in aquatic stages. We also found a higher concentration of SGE-IgG antibodies in people exposed to DENV, a positive correlation between IgM-SGE and IgG-DENV and a negative correlation with IgG-SGE. CONCLUSION: Anti-salivary proteins antibodies are consistent with the presence of Ae. aegypti aquatic stages inside houses and DENV-IgG antibodies concentrations. PMID- 26844448 TI - [Performance assessment employing slide sets: A tool for the classification of senior microscopists from Colombia's Malaria Control Program]. AB - INTRODUCTION: One of the most important activities for quality assurance of malaria diagnosis is performance assessment. In Colombia, performance assessment of malaria microscopists has been done through the external performance assessment and indirect external performance assessment programs. OBJECTIVES: To assess the performance of malaria microscopists of public reference laboratories using slide sets, and to describe the methodology used for this purpose. MATERIALS AND METHODS: This was a retrospective study to evaluate the concordance of senior microscopists regarding parasite detection, species identification and parasite count based on the results of the assessment of competences using two sets, one comprising 40 slides, and another one with 17 slides. RESULTS: The concordance for parasite detection was 96.9% (95% CI: 96.0-97.5) and 88.7% (95% CI: 86.6-90.5) for species identification. The average percentage of concordant slides in the group evaluated was 89.7% (95% CI: 87.5-91.6). CONCLUSIONS: Most of the senior microscopists in Colombia were classified in the two top categories in the performance assessment using slide sets. The most common difficulty encountered was the identification of parasite species. The use of this tool to assess individual performance of microscopists in the evaluation of samples with different degrees of difficulty allows for characterizing the members of the malaria diagnosis network and strengthening the abilities of those who require it. PMID- 26844449 TI - The Diagnostic Performance of Stool DNA Testing for Colorectal Cancer: A Systematic Review and Meta-Analysis. AB - This meta-analysis was designed to evaluate the diagnostic performance of stool DNA testing for colorectal cancer (CRC) and compare the performance between single-gene and multiple-gene tests.MEDLINE, Cochrane, EMBASE databases were searched using keywords colorectal cancers, stool/fecal, sensitivity, specificity, DNA, and screening. Sensitivity analysis, quality assessments, and performance bias were performed for the included studies.Fifty-three studies were included in the analysis with a total sample size of 7524 patients. The studies were heterogeneous with regard to the genes being analyzed for fecal genetic biomarkers of CRC, as well as the laboratory methods being used for each assay. The sensitivity of the different assays ranged from 2% to 100% and the specificity ranged from 81% to 100%. The meta-analysis found that the pooled sensitivities for single- and multigene assays were 48.0% and 77.8%, respectively, while the pooled specificities were 97.0% and 92.7%. Receiver operator curves and diagnostic odds ratios showed no significant difference between both tests with regard to sensitivity or specificity.This meta-analysis revealed that using assays that evaluated multiple genes compared with single gene assays did not increase the sensitivity or specificity of stool DNA testing in detecting CRC. PMID- 26844450 TI - Dopaminergic Therapy Modulates Cortical Perfusion in Parkinson Disease With and Without Dementia According to Arterial Spin Labeled Perfusion Magnetic Resonance Imaging. AB - Arterial spin labeling (ASL) magnetic resonance imaging analyses allow for the quantification of altered cerebral blood flow, and provide a novel means of examining the impact of dopaminergic treatments. The authors examined the cerebral perfusion differences among 17 Parkinson disease (PD) patients, 17 PD with dementia (PDD) patients, and 17 healthy controls and used ASL-MRI to assess the effects of dopaminergic therapies on perfusion in the patients. The authors demonstrated progressive widespread cortical hypoperfusion in PD and PDD and robust effects for the dopaminergic therapies. Specifically, dopaminergic medications further decreased frontal lobe and cerebellum perfusion in the PD and PDD groups, respectively. These patterns of hypoperfusion could be related to cognitive dysfunctions and disease severity. Furthermore, desensitization to dopaminergic therapies in terms of cortical perfusion was found as the disease progressed, supporting the concept that long-term therapies are associated with the therapeutic window narrowing. The highly sensitive pharmaceutical response of ASL allows clinicians and researchers to easily and effectively quantify the absolute perfusion status, which might prove helpful for therapeutic planning. PMID- 26844451 TI - Inverse Association of Serum Docosahexaenoic Acid With Newly Diagnosed Hypertension: A Community-based Case-control Study. AB - Observational studies on circulating fatty acid (FA) and primary prevention of hypertension have yielded inconsistent results, and the association among the Chinese population is not fully clear. The aim of the study was to discern important FAs that can discriminate hypertensive patients from normotensive persons, and investigate associations between the important FAs and risk of hypertension.We conducted a case-control study nested within a community-based cohort of 2447 Chinese participants aged 35 to 79 years who completed a baseline assessment between October 2012 and April 2013. In all, 480 patients with newly diagnosed hypertension were identified at baseline and 480 normotensive individuals were randomly selected as matched normotensive controls. Controls were individually matched to cases by age (+/-2 y), sex, and recruitment center, with a 1:1 case-to-control ratio. Serum FA profile was compared between cases and controls by orthogonal partial least squares-discriminant analyses. Odds ratio (OR) with 95% confidence interval (CI) for newly diagnosed hypertension was estimated by a conditional logistical analysis.After adjustment for body mass index, education, profession, family history of hypertension, salt intake, heart rate, blood lipids, and fasting glucose levels, serum FA profile in hypertensive patients was typically characterized by higher 16:0 and 16:1n-7, and lower 18:2n 6 and 22:6n-3, compared with normotensive controls. Docosahexaenoic acid (22:6n 3) and palmitoleic acid (16:1n-7) were identified as the important FA contributing most to the intergroup separations. When comparing the highest and lowest quartile of FA composition, newly diagnosed hypertension was negatively associated with 22:6n-3 (OR 0.65; 95% CI, 0.45-0.93; P for trend = 0.02), but positively associated with 16:1n-7 (OR 2.14; 95% CI, 1.46-3.12; P for trend < 0.001). The associations remained pronounced after multiple adjustments and in further stratified analyses.In distinguishing hypertensive patients and normotensive persons, 22:6n-3 was considered as an important n-3 FA. Increased serum proportion of 22:6n-3 was associated with decreased odds of newly diagnosed hypertension, which suggests that high levels of 22:6n-3 in serum or perhaps in diet may be beneficial for prevention of hypertension in the Chinese population. PMID- 26844452 TI - Function of Treg Cells Decreased in Patients With Systemic Lupus Erythematosus Due To the Effect of Prolactin. AB - Prolactin has different functions, including cytokine secretion and inhibition of the suppressor effect of regulatory T (Treg) cells in healthy individuals. Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by defects in the functions of B, T, and Treg cells. Prolactin plays an important role in the physiopathology of SLE. Our objective was to establish the participation of prolactin in the regulation of the immune response mediated by Treg cells from patients with SLE. CD4CD25CD127 cells were purified using magnetic beads and the relative expression of prolactin receptor was measured. The functional activity was evaluated by proliferation assay and cytokine secretion in activated cells, in the presence and absence of prolactin. We found that both percentage and function of Treg cells decrease in SLE patients compared to healthy individuals with statistical significance. The prolactin receptor is constitutively expressed on Treg and effector T (Teff) cells in SLE patients, and this expression is higher than in healthy individuals. The expression of this receptor differs in inactive and active patients: in the former, the expression is higher in Treg cells than in Teff cells, similar to healthy individuals, whereas there is no difference in the expression between Treg and Teff cells from active patients. In Treg:Teff cell cocultures, addition of prolactin decreases the suppressor effect exerted by Treg cells and increases IFNgamma secretion. Our results suggest that prolactin plays an important role in the activation of the disease in inactive patients by decreasing the suppressor function exerted by Treg cells over Teff cells, thereby favoring an inflammatory microenvironment. PMID- 26844453 TI - Comparison of 1-Site and 2-Site Phacotrabeculectomy in the Small Adult Eyes With Concomitant Cataract and Glaucoma. AB - The aim of this study was to compare the outcomes after phacotrabeculectomy at 1 or 2 sites in the small adult eyes with concomitant cataract and glaucoma.Patients who had 1-site (n = 26) or 2-site (n = 14) phacotrabeculectomy over a 4-year period at an eye surgery center were included. Eighteen eyes of 18 patients with glaucoma using any 1 prostaglandin analogue (latanoprost, travoprost, or bimatoprost) were compared with 8 normal control patients. The records of patients were reviewed, and intraocular pressure, best-corrected visual acuity, axial length, anterior chamber depth, corneal endothelial cell (CEC) density, Diopter were measured. The outcome was compared with postoperative and preoperative measurements for 3-month follow-ups.The follow-up time was 3 months. There was no difference between the operations in improving best corrected visual acuity, lowering intraocular pressure, shortening axial length, and deepening anterior chamber depth. However, 2-site surgery was associated with significantly more CEC loss and refractive error. Postoperative complications were not different between the 2 groups.The CEC loss and the refractive error in 2-site group were higher than that of 1-site group. One-site surgery seems to cause less CEC damage and refractive error than the 2-site operation during the follow-up time of 3 months. PMID- 26844454 TI - Carvedilol, Bisoprolol, and Metoprolol Use in Patients With Coexistent Heart Failure and Chronic Obstructive Pulmonary Disease. AB - Beta (beta)-blockers are under-prescribed in patients with heart failure (HF) and concurrent chronic obstructive pulmonary disease (COPD) due to concerns about adverse pulmonary effects and a poor understanding of the effects of these drugs. We aimed to evaluate the survival effects of beta-blockers in patients with coexistent HF and COPD. Using the Taiwan National Health Insurance Research Database, we conducted a nationwide population-based study. Patients with coexistent HF and COPD diagnosed between 2000 and 2009 were enrolled. Doses of the 3 beta-blockers proven to be beneficial to HF (carvedilol, bisoprolol, and metoprolol) during the study period were extracted. The primary endpoint was cumulative survival. Patients were followed until December 31, 2009. The study included 11,558 subjects, with a mean follow-up period of 4.07 years. After adjustment for age, sex, comorbidities, and severity of HF and COPD, bisoprolol use showed a dose-response survival benefit [low dose: adjusted hazard ratio (HR) = 0.76, 95% confidence interval (CI) = 0.59-0.97, P = 0.030; high dose: adjusted HR = 0.40, 95% CI = 0.26-0.63, P < 0.001] compared with nonusers, whereas no survival difference was observed for carvedilol or metoprolol. Compared with patients with HF alone, this special HF + COPD cohort received significantly fewer targeted beta-blockers (108.8 vs 137.3 defined daily doses (DDDs)/person year, P < 0.001) and bisoprolol (57.9 vs 70.8 DDDs/person-year, P < 0.001). In patients with coexisting HF and COPD, this study demonstrated a dose-response survival benefit of bisoprolol use, but not of carvedilol or metoprolol use. PMID- 26844456 TI - Anemia on Admission Is an Independent Predictor of Long-Term Mortality in Hip Fracture Population: A Prospective Study With 2-Year Follow-Up. AB - Anemia is a disputable factor for long-term mortality in hip fracture population in previous studies. Previous studies indicated that the level of hemoglobin (Hb) might fluctuate due to various factors, such as comorbidities and in-hospital interventions, and the changing level of Hb, may lead to discordance diagnosis of anemia and thus to the conflicting conclusions on prognostic value of anemia. So in this study, we aim to compare factors affecting the diagnosis of anemia at different time-points, admission, postoperation, and discharge, and to determine which the time point is most suitable for mortality prediction.This prospective cohort study included 1330 hip fracture patients from 1 January 2000 to 18 November 2012. Hb levels at 3 different time points, such as admission, postoperation, and discharge, were collected and used to stratify the cohort into anemia and nonanemia groups. Candidate factors including commodities, perioperative factors, blood transfusion, and other in-hospital interventions were collected before discharge. Logistic regression analyses were performed to detect risk factors for anemia for the 3 time points separately. Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the association between anemia and 2-year mortality.Factors affecting the diagnosis of anemia were different for the 3 time points. Age, female sex, American Society of Anesthesiologists score (ASA), and intertrochanteric fracture were associated with admission anemia, while surgical procedure, surgical duration, blood transfusion, blood loss during the operation, and drainage volume were major risk factors for postoperation anemia. Cox proportional-hazards regression analysis suggested that the risk of all-cause mortality was higher in the anemia group on admission (1.680, 95%CI: 1.201-2.350, P < 0.01), but not postoperation or on discharge, after adjustment for confounding factors.Our study showed that risk factors for anemia varied at different time points, and therapy interventions would greatly affect the status of postoperation and discharge anemia in hip fracture patients. The take-home message is when anemia is used for mortality prediction in these patients, a specific time point should be chosen. We suggest that only admission anemia should be used for mortality prediction, but not postoperation nor discharge anemia. PMID- 26844455 TI - Interventions That Affect Gastrointestinal Motility in Hospitalized Adult Patients: A Systematic Review and Meta-Analysis of Double-Blind Placebo Controlled Randomized Trials. AB - Gastrointestinal (GI) dysmotility is a common complication in acute, critically ill, postoperative, and chronic patients that may lead to impaired nutrient delivery, poor clinical, and patient-reported outcomes. Several pharmacological and nonpharmacological interventions to treat GI dysmotility were investigated in dozens of clinical studies. However, they often yielded conflicting results, at least in part, because various (nonstandardized) definitions of GI dysmotility were used and methodological quality of studies was poor. While a universally accepted definition of GI dysmotility is yet to be developed, a systematic analysis of data derived from double-blind placebo-controlled randomized trials may provide robust data on absolute and relative effectiveness of various interventions as the study outcome (GI motility) was assessed in the least biased manner.To systematically review data from double-blind placebo-controlled randomized trials to determine and compare the effectiveness of interventions that affect GI motility.Three electronic databases (MEDLINE, SCOPUS, and EMBASE) were searched. A random effects model was used for meta-analysis. The summary estimates were reported as mean difference (MD) with the corresponding 95% confidence interval (CI).A total of 38 double-blind placebo-controlled randomized trials involving 2371 patients were eligible for inclusion in the systematic review. These studies investigated a total of 20 different interventions, of which 6 interventions were meta-analyzed. Of them, the use of dopamine receptor antagonists (MD, -8.99; 95% CI, -17.72 to -0.27; P = 0.04) and macrolides (MD, 26.04; 95% CI, -51.25 to -0.82; P = 0.04) significantly improved GI motility compared with the placebo group. The use of botulism toxin significantly impaired GI motility compared with the placebo group (MD, 5.31; 95% CI, -0.04 to 10.67; P = 0.05). Other interventions (dietary factors, probiotics, hormones) did not affect GI motility.Based on the best available data and taking into account the safety profile of each class of intervention, dopamine receptor antagonists and macrolides significantly improve GI motility and are medications of choice in treating GI dysmotility. PMID- 26844457 TI - Changes in Socioeconomic Inequality of Low Birth Weight and Macrosomia in Shaanxi Province of Northwest China, 2010-2013: A Cross-sectional Study. AB - Socioeconomic disparities in birth weights (BWs) are associated with lifelong differences in health and productivity. Understanding socioeconomic disparities in BW is presently of concern to develop public health interventions that promote a good start in life in Northwest China. In the study, our objective is to investigate the socioeconomic disparities in low and high BW from 2010 to 2013 in this region.Those single live births were recruited using a stratified multistage sampling method in Shaanxi province from August to December 2013. Data were collected with a structured questionnaire and a review of birth certificates. Socioeconomic status (SES) was stratified based on the calculated household wealth index. Prevalence differences (PDs) and concentration indices (CIs) were used to depict the SES inequality of low BW (LBW) and macrosomia.Information for 28722 single live births born were obtained in Shaanxi province. From 2010 to 2013, the overall rates of LBW decreased, and the difference in LBW across differing SES groups decreased by 0.7% (boys, 0.4%; girls, 0.8%). From 2010 to 2013, the overall rates of macrosomia increased by 14.3% (boys, 17.5%; girls, 7.8%), whereas the PDs in macrosomia across various SES groups remained unchanged. From 2010 to 2013, concentration indices for SES inequalities in LBW and macrosomia confirmed the results shown by differences in prevalence. Compared with mothers of high SES, those in low SES group were significantly older, less educated, engaged in farming with less availabile healthcare, and engaged in unhealthy lifestyles (eg, exposure to secondhand smoke) during pregnancy, regardless of the baby's sex.From 2010 to 2013, in Shaanxi province, the negative association between socioeconomic status and LBW weakened. Rates of macrosomia were higher in those of high SES, but the SES disparities varied insignificantly over the same time. Our findings may provide valuable insights to direct healthcare policies for pregnant women to reduce inequalities in health, quality of life, and productivity for their children as they age into adulthood. PMID- 26844458 TI - Outcomes Between Elderly and Young Hepatocellular Carcinoma Living Donor Liver Transplantation Recipients: A Single-Center Experience. AB - Although older age theoretically might be a negative risk factor for liver transplantation (LT) outcomes, age alone should not exclude a patient from waiting list. This study is to investigate the outcomes of elderly hepatocellular carcinoma (HCC) living donor liver transplantation (LDLT) recipients which meet Milan criteria.A retrospective study was performed in a single liver transplantation center. Demographic and clinical data of 110 HCC LDLT recipients from January 2004 to December 2012 were collected and analyzed, including 31 elderly recipients in group E (>= 60 years) and 79 younger recipients in group Y (<60 years).Recipients' age between 2 groups were significantly different (65.4 +/- 4.8 vs 49.9 +/- 5.9, P = 0.000). There was no significant difference in preoperative demographic data as well as postoperative liver function. Complication rates, length of ICU and hospital stay, graft loss, and mortality were similar in both groups, as well as the 1-, and 3-year overall and disease free survival rates (77.4%, and 64.5% vs 82.8%, and 44.6%, P = 0.458; 94.7%, and 80.7% vs 98.6%, and 85.9%, P = 0.661). When recipients were further stratified into group E1, E2, Y1, and Y2, no significant difference was found in 1-, and 3 year overall and disease-free survival rates. In multivariate analysis, recipients' age was not a predictor for long-term survival.Following rigorous listing criteria, if overall clinical conditions and comorbidities allowed, elderly HCC recipients achieved similar LDLT outcomes and survival rates with the younger HCC recipients. PMID- 26844459 TI - Investigation of the Existence of Supplier-Induced Demand in use of Gastrostomy Among Older Adults: A Retrospective Cohort Study. AB - The aim of this study is to clarify whether there is small area variation in the use of gastrostomy that is explained by hospital physician density, so as to detect the existence of supplier-induced demand (SID).The study design is a retrospective cohort using claim data of Fukuoka Late Elders' Health Insurance, submitted from 2010 to 2013. Study participants included 51,785 older adults who had been diagnosed with eating difficulties. We designated use of gastrostomy as an event. Multilevel logistic analyses were then used to investigate the existence of SID.After controlling for patient factors, we found significant regional level variance in gastrectomy use (median odds ratio [MOR]: 1.72, 1.37 2.51). Hospital physician density was significantly positively related with gastrostomy (adjusted OR of hospital physician density: 1.75, 1.25-2.45; P < 0.001). MORs were largely reduced for the input variable of hospital physician density.We found that the small area variation in use of gastrostomy among older adults could be explained by hospital physician density, which might indicate the existence of SID. PMID- 26844460 TI - Bullying, Depression, and Suicidal Ideation Among Adolescents in the Fujian Province of China: A Cross-sectional Study. AB - The relationship of bullying with suicidal ideation among adolescents is controversial. Although depression has been related to bullying and suicidal ideation, little is known about the combined impacts of depression and bullying on suicidal ideation.A sample of 20,509 high school students from Fujian Province were selected randomly by multistage stratified sampling. All participants completed an adolescent health status questionnaire. Three categories of bullying were assessed: perpetration, victimization, and both (victimization and perpetration). The associations of these 3 categories of bullying with depression and their interaction with suicidal ideation were examined in logistic models.After adjustment for potential confounders, all 3 categories of bullying (perpetration, victimization, and both) were related to increased risk of suicidal ideation with odds ratios (ORs) of 1.66 (95% confidence interval [CI] 1.20-2.30), 2.74 (95% CI 2.29-3.29), and 2.83 (95% CI 2.27-3.52), respectively. There was an interaction between depression and bullying (P = 0.001). Subgroup analyses showed a stronger association between perpetration and suicidal ideation in students with depression (odds ratio [OR] 2.97; 95% CI 1.44-6.09) than in those without depression (OR 1.65; 95% CI 1.19-2.28). The association between victimization and suicidal ideation was weaker in students with depression (OR 1.49; 95% CI 1.07-2.07) than in those without (OR 2.69; 95% CI 2.24-3.23). The association of both victimization and perpetration with suicidal ideation was weaker in students with depression (OR 2.22, 95% CI 1.43-3.47) than those without (OR 2.78; 95% CI 2.23-3.47).We observed an independent association of bullying with increased risk of suicidal ideation among adolescent students, and this association was affected by depression. Prospective studies should be conducted to confirm these findings. PMID- 26844461 TI - Hospitalization for Pneumonia is Associated With Decreased 1-Year Survival in Patients With Type 2 Diabetes: Results From a Prospective Cohort Study. AB - Diabetes mellitus is a frequent comorbid conditions among patients with pneumonia living in the community.The aim of our study is to evaluate the impact of hospitalization for pneumonia on early (30 day) and late mortality (1 year) in patients with type 2 diabetes mellitus.Prospective comparative cohort study of 203 patients with type 2 diabetes hospitalized for pneumonia versus 206 patients with diabetes hospitalized for other noninfectious causes from January 2012 to December 2013 at Policlinico Umberto I (Rome). Enrolled patients were followed up to discharge and up to 1 year after initial hospital admission or death.Overall, 203 patients with type 2 diabetes admitted to hospital for pneumonia were compared to 206 patients with type 2 diabetes admitted for other causes (39.3% decompensated diabetes, 21.4% cerebrovascular diseases, 9.2% renal failure, 8.3% acute myocardial infarction, and 21.8% other causes). Compared to control patients, those admitted for pneumonia showed a higher 30-day (10.8% vs 1%, P < 0.001) and 1-year mortality rate (30.3% vs 16.8%, P < 0.001). Compared to survivors, nonsurvivor patients with pneumonia had a higher incidence of moderate to severe chronic kidney disease, hemodialysis, and malnutrition were more likely to present with a mental status deterioration, and had a higher number of cardiovascular events during the follow-up period. Cox regression analysis found age, Charlson comorbidity index, pH < 7.35 at admission, hemodialysis, and hospitalization for pneumonia as variables independently associated with mortality.Hospitalization for pneumonia is associated with decreased 1-year survival in patients with type 2 diabetes, and appears to be a major determinant of long-term outcome in these patients. PMID- 26844462 TI - Systematic Review and Meta-Analysis of Pancreatic Amylase Value on Postoperative Day 1 After Pancreatic Resection to Predict Postoperative Pancreatic Fistula. AB - Early detection of postoperative pancreatic fistula (POPF) may help to improve the outcome following pancreatic surgery, and exclusion of POPF may allow early drain removal which can accelerate recovery. The aim of this study was to evaluate the diagnostic accuracy of drain/plasma pancreatic amylase values on postoperative day 1 (DPA1/PPA1) in POPF by means of a systemic review and meta analysis.Online journal databases and a manual search up to March 2015 were used. Studies clearly documenting DPA1 or PPA1 in predicting overall POPF (Grade 0 vs A+B+C) or clinically relevant POPF (Grade 0+A vs B+C) following pancreatic surgery were selected. Pooled predictive parameters were performed using STATA 12.0.Fifteen studies were finally identified with a total of 4331 patients. The pooled sensitivity and specificity of DPA1 were 0.92 (95% confidence interval (CI) 0.81-0.96) and 0.77 (95% CI 0.64-0.86) for predicting overall POPF and 0.79 (95% CI 0.61-0.90) and 0.83 (95% CI 0.74-0.89) for predicting clinically relevant POPF. The pooled sensitivity and specificity of PPA1 were 0.74 (95% CI 0.63-0.82) and 0.62 (95% CI 0.55-0.70) for overall POPF. After the DPA1 at/over cutoff values for overall POPF or clinically relevant POPF, corresponding post-test probability (Post-test (+)) (if pretest probability was 50%) was 80% and 82% respectively, while, if values were below the cutoff values, the post-test probability (Post-test (-)) was 10% and 20% respectively. Post-test (+) and Post test (-) of PPA1 for overall POPF were 66% and 30% respectively. In subgroup analysis, the summary sensitivities of cutoff <1000 group and cutoff >1000 group were 0.96 (0.92-0.98) and 0.85 (0.64-0.95), respectively; the summary specificities were 0.59 (0.44-0.72) and 0.86 (0.80-0.91) respectively. Positive LR were 2.3 (1.7-3.3) and 6.2 (3.7-10.2) respectively. Negative LR were 0.06 (0.03-0.14) and 0.18 (0.07-0.47) respectively.DPA1 is a useful predictive test for overall POPF and clinically relevant POPF which has good sensitivity and specificity based on the current studies. Meanwhile, it should be cautiously applied to clinical practice because cutoffs had a wide range between studies. PMID- 26844463 TI - Management of Heterotopic Pregnancy: Experience From 1 Tertiary Medical Center. AB - The objective of this study is to summarize the experiences of our department in the management of heterotopic pregnancy (HP) and to analyze the influence of different treatment modality on the viable intrauterine pregnancy.There were 64 patients diagnosed as HP in the Department of Gynecology and Obstetrics in our hospital between January 2003 and June 2014, 52 HP patients with viable intrauterine pregnancy were included and analyzed in our study. Interventions included expectant management, surgical management and transabdominal sonographic guided transvaginal aspiration of ectopic gestational embryo (embryo aspiration) management.Main outcome measures are maternal outcome and pregnancy outcome.In expectant management group, 4 patients suffered rupture of ectopic pregnancy, 6 patients transferred to surgical management, 1 patient suffered a fever of 40.4 degrees C, the abortion rate was 5% (1/20). In surgical management group, emergency surgery was performed in 9 patients with unstable hemodynamics and 3 patients with stable hemodynamics, 1 patient suffered uterine rupture 5 weeks later and dead fetus was demonstrated, 1 patient suffered urinary retention postoperative, the abortion rate was 14.8% (4/27). In embryo aspiration management group, 1 patient needed another embryo aspiration, all patients were eventful and no abortion was observed.In our retrospective study, transabdominal sonographic guided aspiration of ectopic gestational embryo has the best maternal outcome and the lowest abortion rate, surgical management group shows the highest abortion rate, and expectant management presents the worst maternal outcome. PMID- 26844464 TI - Auscultation of Velcro Crackles is Associated With Usual Interstitial Pneumonia. AB - Auscultation of Velcro crackles has been proposed as a key finding in physical lung examination in patients with interstitial lung diseases (ILDs), especially in idiopathic pulmonary fibrosis (IPF). However, no studies have been carried out to assess the association of Velcro crackles with other clinical variables.We evaluated a cohort of 132 patients, prospectively and consecutively included in our ILD diagnostic program at a tertiary referral center. All patients were auscultated during the physical examination. The patients were divided into 2 groups: "presence" or "nonpresence" of bilateral Velcro crackles.Of all patients assessed, 83 (63%) presented Velcro crackles in the respiratory auscultation. Patients with Velcro crackles usually had more frequently cough and dyspnea at the moment of diagnosis. Forced vital capacity (P = 0.002) and lung diffusion capacity for carbon monoxide (P = 0.04) was lower in these patients. The ILD-GAP index was higher in the group with Velcro crackles (P = 0.01). All patients with usual interstitial pneumonia (UIP) in high-resolution computed tomography and all patients with final IPF diagnosis presented Velcro crackles. In multivariate analysis, the presence of Velcro crackles was independently associated with an UIP pattern.In patients suspected of having ILD, the auscultation of Velcro crackles was associated with UIP, a possibility which must be taken into consideration in early ILD detection in primary care. PMID- 26844465 TI - Impact of Chronic Kidney Disease on Short-Term Cardiac Implantable Electronic Device Related Infection: A Nationwide Population-Based Cohort Study. AB - Chronic kidney disease (CKD) increased the incident cardiac implantable electronic device (CIED) infection, but risk factors of CIED infection in CKD patients remain unclear.Patients who received new CIED implantation between January 1, 1997 and December 31, 2011 were selected from the Taiwan National Health Insurance Database and were divided into 3 groups: patients with normal renal function, CKD patients without dialysis, and CKD patient with dialysis. Two outcomes, CIED infection during index hospitalization and within 1 year after discharge, were evaluated.This study included 38,354 patients, 35,060 patients in normal renal function group, 1927 patients in CKD without dialysis group, and 1367 patients in CKD with dialysis group. CKD patients without dialysis (adjusted odds ratio [aOR], 2.14, 95% confidence interval [CI], 1.32-3.46) and CKD patients with dialysis (aOR, 3.78, 95% CI, 2.37-6.02) increased incident CIED infection during index hospitalization compared to patients with normal renal function. Use of steroid (aOR: 2.74, 95% CI, 1.08-6.98) increased the risk of CIED infection in CKD patients without dialysis while chronic obstructive pulmonary disease (COPD) (aOR: 2.76, 95% CI, 1.06-7.16) increased the risk of CIED infection in CKD patient with dialysis during index hospitalization.CKD is a risk of CIED infection during index hospitalization. Use of steroid and COPD are important risks factors for CIED infection in CKD patients. PMID- 26844466 TI - Influenza Vaccination is Associated with Lower Risk of Acute Coronary Syndrome in Elderly Patients with Chronic Kidney Disease. AB - Elderly patients with chronic kidney disease (CKD) are at a higher risk of hospitalization for cardiovascular diseases (CVD). Previous studies have showed that influenza vaccination could reduce the risk of recurrent major cardiovascular events in patients with CVD. However, the effects of influenza vaccination on the reduction of first hospitalizations for acute coronary syndrome (ACS) in elderly patients with CKD remain unknown.We conducted a cohort study using data from the Taiwan Longitudinal Health Insurance Database 1997 to 2008. This cohort study comprised elderly patients (ages >=55 years) with a recorded diagnosis of CKD (n = 4406) between January 1, 1999, and December 31, 2007. Each patient was followed up until the end of 2008. To minimize the selection bias of vaccine therapy, a propensity score adjustment was applied. The hazard ratio (HR) and 95% confidence interval (CI) for the association between the influenza vaccination and the occurrence of first hospitalization for ACS was evaluated by Cox proportional hazards regression. We further categorized the patients into 4 groups according to their vaccination status (unvaccinated, and total number of vaccinations: 1, 2-3, and >=4).We found that elderly CKD patients without prior CVD history receiving influenza vaccination exhibited a lower risk of hospitalization for ACS (adjusted HR = 0.35, 95% CI 0.30-0.42; P < 0.001). We observed consistent protective effects regardless of age groups (55-64, 65-74, and >=75), gender, and seasonality of influenza. When the patients were stratified according to the total number of vaccinations, the adjusted HRs for first ACS hospitalization were 0.62 (95% CI 0.52-0.81), 0.35 (95% CI 0.28-0.45), and 0.13 (95% CI 0.09-0.19) for patients who received 1, 2 to 3, and >=4 vaccinations. There was a significant trend of decreasing risk of ACS hospitalization with an increasing number of vaccinations.The results of our observational study could strengthen the annual vaccination policy and physicians should be aware of missed opportunities to vaccinate elderly patients with CKD against influenza. The potential public health impact of influenza vaccination, particularly in the elderly CKD patients without a history of CVD, who are at risk for ACS, should be further explored. PMID- 26844467 TI - Clinical Characteristics and Surgical Outcomes in Patients With Intermittent Exotropia: A Large Sample Study in South China. AB - The clinical characteristics and surgical outcomes in a large sample of patients with intermittent exotropia (IXT) as well as an analysis of risk factors associated with surgical failures are presented in this article. Data from IXT patients who received surgical management at the Eye Hospital, in the Zhongshan Ophthalmic Center, of Sun Yat-Sen University, China from January 2009 to December 2013 were reviewed retrospectively. Included within this analysis were data from pre- and postoperative ocular motility, primary alignment, and binocular vision.A total of 1228 patients with IXT were reviewed. Males (50.4%) and females (49.6%) were nearly equally represented in this sample. Thirty-two patients (2.6%) had a family history of strabismus. The mean age at onset was 6.77 +/- 6.43 years (range 7 months -48.5 years), mean duration at presentation was 7.35 +/- 6.68 years (range 6 months-47 years), and mean age at surgery was 13.7 +/- 8.8 years (range 3-49 years). The mean refractive error was -0.84 +/- 2.69 diopter in the right eye and -0.72 +/- 2.58 diopter in the left eye. Amblyopia (4.2%), oblique muscle dysfunction (7.0%), and dissociated vertical deviation (4.7%) were also present in these patients. The most common subtype of IXT was the basic type (88.1%). Orthophoria was observed in 80.5% of patients and the ratios of surgical undercorrection and overcorrection were 14.7% and 4.8%, respectively, as determined with a mean follow-up time of 7.8 +/- 3.7 months. When combining ocular alignment with binocular vision as the success criteria, the success rate decreased to 35.6%. Multivariate risk factor analysis showed that only the loss of stereoacuity (P = 0.002) was associated with a poor outcome. There were no differences in the long-term results between bilateral lateral rectus recession and unilateral lateral rectus recession with medial rectus resection.Most IXT patients displayed normal vision, with few having positive family histories, amblyopia, oblique muscle dysfunction, and dissociated vertical deviation. The most common subtype of IXT was the basic type. Long-term surgical results were less favorable when sensory status was included in the criteria for success. Patients with stereoacuity loss were at an increased risk for poor outcomes. PMID- 26844468 TI - Complete Response and Fatigue Improvement With the Combined Use of Cyclophosphamide and Quercetin in a Patient With Metastatic Bladder Cancer: A Case Report. AB - Bladder cancer is a major cause of cancer-related mortality, with an estimated 74,000 new cases and 16,000 deaths in the United States in 2015. In patients with metastatic disease, vinflunine and taxanes are the most widely used chemotherapy agents in the second-line setting after failure of platinum-based treatment. Cyclophosphamide has been used in combination with paclitaxel in urothelial carcinoma of the bladder, but there are no data about the effectiveness of cyclophosphamide administered as a single agent.We here describe the first case of an advanced bladder cancer patient suffering from grade 2 fatigue.He benefited from administration of third-line single-agent metronomic oral cyclophosphamide plus oral doses of quercetin. A complete, prolonged radiologic response according to the RECIST criteria 1.1 was achieved with minimal toxicity and an improvement in fatigue.Further studies are required to assess the potential benefits associated with the combined use of cyclophosphamide plus quercetin in advanced bladder cancer patients. PMID- 26844469 TI - Time-Dependent Serum Brain-Derived Neurotrophic Factor Decline During Methamphetamine Withdrawal. AB - Methamphetamine (METH) is a widely abused illegal psychostimulant, which is confirmed to be neurotoxic and of great damage to human. Studies on the role of brain-derived neurotrophic factor (BDNF) in human METH addicts are limited and inconsistent. The purposes of this study are to compare the serum BDNF levels between METH addicts and healthy controls during early withdrawal, and explore the changes of serum BDNF levels during the first month after METH withdrawal.179 METH addicts and 90 age- and gender-matched healthy controls were recruited in this study. We measured serum BDNF levels at baseline (both METH addicts and healthy controls) and at 1 month after abstinence of METH (METH addicts only).Serum BDNF levels of METH addicts at baseline were significantly higher than controls (1460.28 +/- 490.69 vs 1241.27 +/- 335.52 pg/mL; F = 14.51, P < 0.001). The serum BDNF levels of 40 METH addicts were re-examined after 1 month of METH abstinence, which were significantly lower than that at baseline (1363.70 +/- 580.59 vs 1621.41 +/- 591.07 pg/mL; t = 2.26, P = .03), but showed no differences to the controls (1363.70 +/- 580.59 vs 1241.27 +/- 335.52 pg/mL; F = 2.29, P = 0.13).Our study demonstrated that serum BDNF levels were higher in METH addicts than controls during early withdrawal, and were time dependent decreased during the first month of abstinence. These findings may provide further evidence that increased serum BDNF levels may be associated with the pathophysiology of METH addiction and withdrawal and may be a protective response against the subsequent METH-induced neurotoxicity. Besides, these findings may also promote the development of medicine in the treatment of METH addiction and withdrawal. PMID- 26844470 TI - Severe Infection With Avian Influenza A Virus is Associated With Delayed Immune Recovery in Survivors. AB - Human infection with avian influenza A virus (H7N9) is a concern because of the mortality rate. Previously, we characterized immunological responses during active infection with it and reported evidence of impaired antigen-presenting capability, particularly in severely affected individuals. Here we describe an investigation of immunological responses during a 1-year follow-up of survivors of H7N9 infection. Survivors of H7N9 infection were classified as having had mild (n = 42) or severe infection (n = 26). Their immune status, including human leukocyte antigen-DR expression on monocytes, and their ability to mount cytokine responses were assessed at 1, 3, and 12 months postinfection.The total lymphocyte count and the percentages of different types of lymphocytes had normalized by 1 month postinfection. However, there was evidence of ongoing impairment of immune responses in those who had had severe infection. This included reduced human leukocyte antigen-DR expression on CD14 monocytes, reduced interferon-gamma production by T cells, and higher plasma levels of the matrix metalloproteinases 2, 3, and 9. By 3 months postinfection, these had all normalized.After severe H7N9 infection, recovery of the antigen-presenting capability of monocytes and T cell responses are delayed. This may lead to an increased vulnerability to secondary bacterial infections. PMID- 26844471 TI - Development and Validation of an HIV Risk Exposure and Indicator Conditions Questionnaire to Support Targeted HIV Screening. AB - The aim of our study was to develop a Spanish-structured HIV risk of exposure and indicator conditions (RE&IC) questionnaire. People attending to an emergency room or to a primary clinical care center were offered to participate in a prospective, 1 arm, open label study, in which all enrolled patients filled out our developed questionnaire and were HIV tested. Questionnaire accuracy, feasibility, and reliability were evaluated.Valid paired 5329 HIV RE&IC questionnaire and rapid HIV tests were performed, 69.3% in the primary clinical care center, 49.6% women, median age 37 years old, 74.9% Spaniards, 20.1% Latin Americans. Confirmed hidden HIV infection was detected in 4.1%, while HIV RE&IC questionnaire was positive in 51.2%. HIV RE&IC questionnaire sensitivity was 100% to predict HIV infection, with a 100% negative predictive value. When considered separately, RE or IC items sensitivity decreases to 86.4% or 91%, and similarly their negative predictive value to 99.9% for both of them. The majority of people studied, 90.8% self-completed HIV RE&IC questionnaire. Median time to complete was 3 minutes. Overall HIV RE&IC questionnaire test-retest Kappa agreement was 0.82 (almost perfect), likewise for IC items 0.89, while for RE items was lower 0.78 (substantial).A feasible and reliable Spanish HIV RE&IC self questionnaire accurately discriminated all non-HIV-infected people without missing any HIV diagnoses, in a low prevalence HIV infection area. The best accuracy and reliability were obtained when combining HIV RE&IC items. PMID- 26844472 TI - Thoracolumbar Scoliosis Due to Cryptococcal Osteomyelitis: A Case Report and Review of the Literature. AB - Cryptococcus neoformans causes opportunistic infections in immunocompromised patients, with vertebral osteomyelitis being a very rare involvement.This study is to present a case of thoracolumbar scoliosis occurring in the setting of cryptococcal osteomyelitis.Pharmacological intervention with anticryptococcal medicine and medical management of immune hemolytic anemia were administered. After initial acute stabilization, she underwent spinal debridement and fusion on October 29, 2008. She eventually recovered fully from this episode with no subsequent mechanical instability or neurological deficits on subsequent clinic follow-ups.To the best of our knowledge, there have been no reports describing the onset of spinal cryptococcal osteomyelitis along with immune hemolytic anemia. We suggest a comprehensive algorithm for the diagnosis of vertebral cryptococcal osteomyelitis. PMID- 26844473 TI - Differential Effects of Bariatric Surgery Versus Exercise on Excessive Visceral Fat Deposits. AB - The aim of the present study was to compare differential impacts of bariatric surgery and exercise-induced weight loss on excessive abdominal and cardiac fat deposition.Excessive fat accumulation around the heart may play an important role in the pathogenesis of cardiovascular disease. Recent evidences have suggested that bariatric surgery results in relatively less decrease in epicardial fat compared with abdominal visceral fat and paracardial fat.Sixty-four consecutive overweight or obese subjects were enrolled in the study. Clinical characteristics and metabolic profiles were recorded. The volumes of abdominal visceral adipose tissue (AVAT), abdominal subcutaneous adipose tissue (ASAT), epicardial (EAT), and paracardial adipose tissue (PAT) were measured by computed tomography in the bariatric surgery group (N = 25) and the exercise group (N = 39) at baseline and 3 months after intervention. Subjects in both the surgery and exercise groups showed significant reduction in body mass index (15.97%, 7.47%), AVAT (40.52%, 15.24%), ASAT (31.40, 17.34%), PAT (34.40%, 12.05%), and PAT + EAT (22.31%, 17.72%) (all P < 0.001) after intervention compared with baseline. In both the groups, the decrease in EAT was small compared with the other compartments (P < 0.01 in both groups). Compared with the exercise group, the surgery group had greater loss in abdominal and cardiac visceral adipose tissue (AVAT, ASAT, PAT, EAT+PAT) (P < 0.001), but lesser loss in EAT (P = 0.037).Compared with the exercise group, bariatric surgery results in significantly greater percentage loss of excessive fat deposits except for EAT. EAT, but not PAT, was relatively preserved despite weight reduction in both the groups. The physiological impact of persistent EAT deserves further investigation. PMID- 26844474 TI - Risk Factors Predictive of Recurrence and Progression for Patients Who Suffered Initial Recurrence After Transurethral Resection of Stage pT1 Bladder Tumor in Chinese Population: A Retrospective Study. AB - Bladder cancer is one of the most common malignancies worldwide and the stage pT1nonmuscle invasive bladder cancer (NMIBC) has a high probability of recurrence after initial diagnosis and treatment. However, risk factors predictive of repeated recurrence and progression of pT1 bladder tumors after primary relapse have not been uncovered. Thus, we conducted the retrospective study.A total of 418 patients who suffered initial recurrence after transurethral resection (TUR) of pT1 bladder tumor were selected for the analyses. Clinic information of the patients was retrieved from their medical records. Recurrence-free survival (RFS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using a Cox proportional hazards regression model. The probability of recurrence and progression by multivariate analyses was used as a surrogate marker to construct receiver operating curve (ROC).Results showed that variables including time to prior recurrence time, prior treatment, number of tumor, tumor size, tumor grade, and time of instillation after surgery were associated with the repeated recurrence of pT1 bladder tumor (P < 0.05). The variables including time to prior recurrence time, tumor size, tumor grade, carcinoma in situ (CIS), and time of instillation after surgery were associated with progression of pT1 bladder tumor (P < 0.05). In the present study, the multivariate model showed an area under ROC (AUC) value of 0.754 and 0.798 for tumor recurrence and progression, respectively, which was more effective in prediction than a single risk factor.In conclusion, we have identified several risk factors relevant to RFS and PFS for patients who have had a history of recurrence of pT1 bladder tumor after TUR. These predictive factors may help urologists to stratify patients into distinct risk groups of recurrence and progression, which probably contributes to the individualized treatment for patients. PMID- 26844475 TI - Distribution of Fatal Vibrio Vulnificus Necrotizing Skin and Soft-Tissue Infections: A Systematic Review and Meta-Analysis. AB - Vibrio vulnificus necrotizing skin and soft tissue infections (VNSSTIs), which have increased significantly over the past few decades, are still highly lethal and disabling diseases despite advancing antibiotic and infection control practices. We, therefore, examined the spatiotemporal distribution of worldwide reported episodes and associated mortality rates of VNSSTIs between 1966 and 2014. The PubMed and Cochrane Library databases were systematically searched for observational studies on patients with VNSSTIs. The primary outcome was all-cause mortality. We did random-effects meta-analysis to obtain estimates for primary outcomes; the estimates are presented as means plus a 95% confidence interval (CI). Data from the selected studies were also extracted and pooled for correlation analyses.Nineteen studies of 2227 total patients with VNSSTIs were analyzed. More than 95% of the episodes occurred in the subtropical western Pacific and Atlantic coastal regions of the northern hemisphere. While the number of cases and the number of deaths were not correlated with the study period (rs = 0.476 and 0.310, P = 0.233 and 0.456, respectively), the 5-year mortality rate was significantly negatively correlated with them (rs = -0.905, P = 0.002). Even so, the pooled estimate of total mortality rates from the random-effects meta analysis was as high as 37.2% (95% CI: 0.265-0.479).These data suggest that VNSSTIs are always an important public health problem and will become more critical and urgent because of global warming. Knowing the current distribution of VNSSTIs will help focus education, policy measures, early clinical diagnosis, and appropriate medical and surgical treatment for them. PMID- 26844476 TI - Prediction of Nonalcoholic Fatty Liver Disease Via a Novel Panel of Serum Adipokines. AB - Considering limitations of liver biopsy for diagnosis of nonalcoholic liver disease (NAFLD), biomarkers' panels were proposed. The aims of this study were to establish models based on serum adipokines for discriminating NAFLD from healthy individuals and nonalcoholic steatohepatitis (NASH) from simple steatosis.This case-control study was conducted in patients with persistent elevated serum aminotransferase levels and fatty liver on ultrasound. Individuals with evidence of alcohol consumption, hepatotoxic medication, viral hepatitis, and known liver disease were excluded. Liver biopsy was performed in the remaining patients to distinguish NAFLD/NASH. Histologic findings were interpreted using "nonalcoholic fatty liver activity score." Control group consisted of healthy volunteers with normal physical examination, liver function tests, and liver ultrasound. Binary logistic regression analysis was applied to ascertain the effects of independent variables on the likelihood that participants have NAFLD/NASH.Decreased serum adiponectin and elevated serum visfatin, IL-6, TNF-a were associated with an increased likelihood of exhibiting NAFLD. NAFLD discriminant score was developed as the following: [(-0.298 * adiponectin) + (0.022 * TNF-a) + (1.021 * Log visfatin) + (0.709 * Log IL-6) + 1.154]. In NAFLD discriminant score, 86.4% of original grouped cases were correctly classified. Discriminant score threshold value of (-0.29) yielded a sensitivity and specificity of 91% and 83% respectively, for discriminating NAFLD from healthy controls. Decreased serum adiponectin and elevated serum visfatin, IL-8, TNF-a were correlated with an increased probability of NASH. NASH discriminant score was proposed as the following: [(-0.091 * adiponectin) + (0.044 * TNF-a) + (1.017 * Log visfatin) + (0.028 * Log IL-8) - 1.787] In NASH model, 84% of original cases were correctly classified. Discriminant score threshold value of (-0.22) yielded a sensitivity and specificity of 90% and 66% respectively, for separating NASH from simple steatosis.New discriminant scores were introduced for differentiating NAFLD/NASH patients with a high accuracy. If verified by future studies, application of suggested models for screening of NAFLD/NASH seems reasonable. PMID- 26844477 TI - Comparison of the Pentax Airwayscope, Glidescope Video Laryngoscope, and Macintosh Laryngoscope During Chest Compression According to Bed Height. AB - We aimed to investigate whether bed height affects intubation performance in the setting of cardiopulmonary resuscitation and which type of laryngoscope shows the best performance at each bed height.A randomized crossover manikin study was conducted. Twenty-one participants were enrolled, and they were randomly allocated to 2 groups: group A (n = 10) and group B (n = 11). The participants underwent emergency endotracheal intubation (ETI) using the Airwayscope (AWS), Glidescope video laryngoscope, and Macintosh laryngoscope in random order while chest compression was performed. Each ETI was conducted at 2 levels of bed height (minimum bed height: 68.9 cm and maximum bed height: 101.3 cm). The primary outcomes were the time to intubation (TTI) and the success rate of ETI. The P value for statistical significance was set at 0.05 and 0.017 in post-hoc test.The success rate of ETI was always 100% regardless of the type of laryngoscope or the bed height. TTI was not significantly different between the 2 bed heights regardless of the type of laryngoscope (all P > 0.05). The time for AWS was the shortest among the 3 laryngoscopes at both bed heights (13.7 +/- 3.6 at the minimum bed height and 13.4 +/- 4.7 at the maximum bed height) (all P < 0.017). The TTI of Glidescope video laryngoscope was not significantly shorter than that of Macintosh laryngoscope at the minimum height (17.6 +/- 4.0 vs 19.6 +/- 4.8; P = 0.02).The bed height, whether adjusted to the minimum or maximum setting, did not affect intubation performance. In addition, regardless of the bed height, the intubation time with the video laryngoscopes, especially AWS, was significantly shorter than that with the direct laryngoscope during chest compression. PMID- 26844478 TI - Predictors of High Motivation Score for Performing Research Initiation Fellowship, Master 1, Research Master 2, and PhD Curricula During Medical Studies: A Strobe-Compliant Article. AB - Translational research plays a crucial role in bridging the gap between fundamental and clinical research. The importance of integrating research training into medical education has been emphasized. Predictive factors that help to identify the most motivated medical students to perform academic research are unknown. In a cross-sectional study on a representative sample of 315 medical students, residents and attending physicians, using a comprehensive structured questionnaire we assessed motivations and obstacles to perform academic research curricula (ie, research initiation fellowship, Master 1, Research Master 2, and PhD). Independent predictive factors associated with high "motivation score" (top quartile on motivation score ranging from 0 to 10) to enroll in academic research curricula were derived using multivariate logistic regression analysis. Independent predictors of high motivation score for performing Master 1 curriculum were: "considering that the integration of translational research in medical curriculum is essential" (OR, 3.79; 95% CI, 1.49-9.59; P = 0.005) and "knowledge of at least 2 research units within the university" (OR, 3.60; 95% CI, 2.01-6.47; P < 0.0001). Independent predictors of high motivation score for performing Research Master 2 curriculum were: "attending physician" (OR, 4.60; 95% CI, 1.86-11.37; P = 0.001); "considering that the integration of translational research in medical curriculum is essential" (OR, 4.12; 95% CI, 1.51-11.23; P = 0.006); "knowledge of at least 2 research units within the university" (OR, 3.51; 95% CI, 1.91-6.46; P = 0.0001); and "male gender" (OR, 1.82; 95% CI, 1.02-3.25; P = 0.04). Independent predictors of high motivation score for performing PhD curriculum were: "considering that the integration of translational research in medical curriculum is essential" (OR, 5.94; 95% CI, 2.33-15.19; P = 0.0002) and "knowledge of at least 2 research units within the university" (OR, 2.63; 95% CI, 1.46-4.77; P = 0.001). This is the first study that has identified factors determining motivations and barriers to carry out academic research curricula among undergraduate and postgraduate medical students. Improving these 2 areas will certainly have an impact on a better involvement of the next generation of physicians in translational medicine. PMID- 26844479 TI - Desensitization Using Bortezomib and High-dose Immunoglobulin Increases Rate of Deceased Donor Kidney Transplantation. AB - Combination therapy of intravenous immunoglobulin (IVIG) and rituximab showed a good transplant rate in highly sensitized wait-listed patients for deceased donor kidney transplantation (DDKT), but carried the risk of antibody-mediated rejection. The authors investigated the impact of a new combination therapy of bortezomib, IVIG, and rituximab on transplantation rate.This study was a prospective, open-labeled clinical trial. The desensitization regimen consisted of 2 doses of IVIG (2 g/kg), a single dose of rituximab (375 mg/m), and 4 doses of bortezomib (1.3 mg/m). The transplant rate was analyzed. Anti-Human leukocyte antigen (HLA) DRB antibodies were determined by a Luminex solid-phase bead assay at baseline and after 2, 3, and 6 months in the desensitized patients.There were 19 highly sensitized patients who received desensitization and 17 patients in the control group. Baseline values of class I and II panel reactive antibody (%, peak mean fluorescence intensity) were 83 +/- 16.0 (14952 +/- 5820) and 63 +/- 36.0 (10321 +/- 7421), respectively. Deceased donor kidney transplantation was successfully performed in 8 patients (42.1%) in the desensitization group versus 4 (23.5%) in the control group. Multivariate time-varying covariate Cox regression analysis showed that desensitization increased the probability of DDKT (hazard ratio, 46.895; 95% confidence interval, 3.468-634.132; P = 0.004). Desensitization decreased mean fluorescence intensity values of class I panel reactive antibody by 15.5% (20.8%) at 2 months. In addition, a liberal mismatch strategy in post hoc analysis increased the benefit of desensitization in donor specific antibody reduction. Desensitization was well tolerated, and acute rejection occurred only in the control group.In conclusion, a desensitization protocol using bortezomib, high-dose IVIG, and rituximab increased the DDKT rate in highly sensitized, wait-listed patients. PMID- 26844480 TI - Altered Spontaneous Brain Activity in Betel Quid Dependence: A Resting-state Functional Magnetic Resonance Imaging Study. AB - It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration.Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate.In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate.The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals. PMID- 26844481 TI - Prognostic Value and Clinicopathological Significance of p-stat3 Among Gastric Carcinoma Patients: A Systematic Review and Meta-Analysis. AB - The overexpression of phosphorylated signal transducer and activator of transcription 3 (p-stat3) was detected in a variety of human tumors. The published studies on p-stat3 expression among gastric carcinoma patients remain controversial.In order to clarify the prognosis value of p-stat3 with overall survival and its association with clinicopathological characteristics in gastric carcinoma, we performed a systematic review and meta-analysis.Eligible studies were retrieved by searching PubMed, Embase, Cochrane library, and Chinese biomedical literature service system databases.Studies described the association between p-stat3 expression and clinicopathological characteristics and overall survival in gastric carcinoma patients; p-stat3 expression was detected by immunohistochemistry (IHC).Odds ratio (OR) and hazard ratio (HR) were considered as a measure of evaluating the association in meta-analysis; I was used to assess the heterogeneity across studies; publication bias was assessed with funnel plot, Egger test, and Begg test.Twenty-three studies including 2872 patients which evaluated the p-stat3 expression by IHC in gastric carcinoma were included. The pooled HR (HR = 2.02, 95% CI: 1.49-2.73, P < 0.00001) indicated that the increased p-stat3 expression was significantly associated with poor overall survival. In addition, when we investigated the association between p-stat3 overexpression and clinicopathological characteristics of gastric carcinoma, we found that the increased p-stat3 expression was significantly associated with tumor differentiation (poorly vs well-moderately: OR = 3.70, 95% CI: 1.98-6.93, P < 0.0001) and lymph node metastasis (present vs absent: OR = 2.40, 95% CI: 1.28 4.50, P = 0.007).The different type of primary antibody was used; the assessment methods of p-stat3 positive expression were defined differently; the locations of p-stat3 expression were different; the method of extrapolating HR from Kaplan Meier survival curves did seem to be less reliable than when HR was extracted directly from literatures; sample sizes, the age of patients, and the follow-up durations are different.In conclusion, our meta-analysis indicates that the increased p-stat3 expression may be not only predict poor prognosis, but also be associated with worse tumor differentiation and lymph node metastasis in patients with gastric carcinoma. PMID- 26844482 TI - Prognostic Value of Plasma Epstein-Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era. AB - This study aimed to evaluate the prognostic value of plasma Epstein-Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level < 4000 copies/mL, patients with an EBV DNA >= 4000 copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68 84]) versus (93%, 95% CI [90-96], P < 0.001), DMFS (83%, 95% CI [76-89]) versus (97%, 95% CI [94-99], P < 0.001), and OS (85%, 95% CI [78-92]) versus (98%, 95% CI [95-100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80-6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036-3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647-14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701-8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252-5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients. PMID- 26844483 TI - Economic Evaluation Study (Cheer Compliant) Laser Prostatectomy for Benign Prostatic Hyperplasia: Outcomes and Cost-effectiveness. AB - To determine which surgical treatment for lower urinary tract symptoms, which is suggestive of benign prostatic hyperplasia (BPH), is more cost-effective and yields a better patient's preference. Treatment outcome, cost, and perioperative complications to assess the treatment effectiveness of using laser prostatectomy as a treatment for BPH were investigated in this study.This retrospective study included 100 patients who underwent transurethral resection of prostate (TUR-P) and another 100 patients who received high-powered 120 W (GreenLight HPS) laser prostatectomy between 2005 and 2011.International Prostate Symptom Score and uroflow parameters were collected before the surgery and the uroflow and postvoiding residual volumes were evaluated before treatment and at 3, 6, 12, and 24 months after treatment. The results of 100 treatments after HPS laser prostatectomy were compared with the results of 100 patients who received TUR-P from the same surgeon. Complication rates and admission costs were analyzed.From 2005 to 2011, 200 consecutive patients underwent endoscopic surgery. Study participants were men with BPH with mean age of 71.3 years old. The peak flow rate went from 8.47 to 15.83 mL/s for 3 months after laser prostatectomy. Laser therapy groups showed better improvement in symptom score, shortened length of stay, and quality of life score when compared with those of TUR-P procedures. The estimated cost for laser prostatectomy was high when compared with cost of any other TUR-P procedural option at Chang Gung Hospital (P = 0.001). All admission charges were similar except for the cost of the laser equipment and accessories (mainly the laser fiber) (P = 0.001). Due to this cost of equipment, it increased the total admission charges for the laser group and therefore made the cost for the laser group higher than that of the TUR-P group.Perioperative complications, such as the need for checking for bleeding, urinary retention rate or urosepsis rate within 30 days after the surgery, held no significant differences between both groups.Compared with alternative treatment options, laser prostatectomy of the prostate is clinically effective but yields a high cost of treatment for symptomatic BPH. PMID- 26844484 TI - Increased Risk of Restless Legs Syndrome in Patients With Migraine: A Nationwide Population-Based Cohort Study. AB - Previous studies suggest that an association between restless legs syndrome (RLS) and migraine exists. However, population-based data are unavailable in Asian cohorts. Our study thus aims to evaluate the association between migraine and RLS in a nationwide, population-based cohort in Taiwan and to examine the effects of age, sex, migraine subtype, and comorbidities on RLS development.Data from the Taiwan National Health Insurance Research Database were used. Patients aged 20 years or older with newly diagnosed migraine from 2000 to 2008 were included; 23,641 patients with newly diagnosed migraine and 94,564 subjects without migraine were randomly selected and followed until RLS development, withdrawal from the National Health Insurance, or until the end of 2011. A multivariate Cox proportional hazards regression model was used to explore the risk of RLS in patients with migraine after adjustment for demographic characteristics and comorbidities.Both cohorts were followed for a mean of 7.38 years. After adjustment for covariates, the risk of RLS was 1.42-fold higher (95% confidence interval = 1.13-1.79) in the migraine cohort than in the nonmigraine cohort (7.19 versus 3.42 years per 10,000 person-years). The increased risk was more prominent in males in the migraine cohort (1.87-fold increased risk, 95% confidence interval 1.22-2.85). Neither comorbidity status nor migraine subtype influenced the RLS risk.This population-based study demonstrated that migraine is associated with an increased risk of RLS compared with those without migraine, particularly in male patients with migraine and regardless of the comorbidity status. PMID- 26844485 TI - Antiphospholipids Syndrome Complicated by a Systemic Capillary Leak-Like Syndrome Treated With Steroids and Intravenous Immunoglobulins: A Case Report. AB - This report describes the onset of systemic capillary leak (SCL)-like syndrome in a 30-year-old woman with antiphospholipids syndrome (APS) during puerperium.Twelve hours after a cesarean section, she presented a sudden fever and abdominal pains followed by dyspnea, severe edema of the limbs and pelvis.Computer tomography shows congestion of interstitial pulmonary parenchyma, pericardial and pleural effusion, edema of intestinal wall and of perivisceral adipose tissue, and periportal lymphedema. Laboratory tests showed neutrophilic leukocytosis, hypoalbuminemia, and an increase of erythrocyte sedimentation rate and C-reactive protein. Because fever and raised inflammation parameters are not observed in idiopathic capillary leak syndrome (SCLS; Clarkson disease), a diagnosis of SCL-like syndrome was made.Albumin solution, high-dose methylprednisolone and intravenous immunoglobulins (IVIG) infusion were administered with a rapid improvement of her clinical condition.The prompt treatment with steroids and IVIG likely prevented the life-threatening shock syndrome that can occur in SCLS, with acute hypotensive attacks, and severe limbs edema requiring fasciotomy.All clinical and laboratory findings supported autoinflammation as the underlying pathogenic mechanism of the syndrome. The data indicate that SCL-like syndrome can be considered a novel clinical syndrome, which can complicate APS. PMID- 26844486 TI - Comparison of Acute Kidney Injury After Robot-Assisted Laparoscopic Radical Prostatectomy Versus Retropubic Radical Prostatectomy: A Propensity Score Matching Analysis. AB - Acute kidney injury (AKI) is associated with extended hospital stay, a high risk of progressive chronic kidney diseases, and increased mortality. Patients undergoing radical prostatectomy are at increased risk of AKI because of intraoperative bleeding, obstructive uropathy, older age, and preexisting chronic kidney disease. In particular, robot-assisted laparoscopic radical prostatectomy (RALP), which is in increasing demand as an alternative surgical option for retropubic radical prostatectomy (RRP), is associated with postoperative renal dysfunction because pneumoperitoneum during RALP can decrease cardiac output and renal perfusion. The objective of this study was to compare the incidence of postoperative AKI between RRP and RALP.We included 1340 patients who underwent RRP (n = 370) or RALP (n = 970) between 2013 and 2014. Demographics, cancer related data, and perioperative laboratory data were evaluated. Postoperative AKI was determined according to the Kidney Disease: Improving Global Outcomes criteria. Operation and anesthesia time, estimated blood loss, amounts of administered fluids and transfused packed red blood cells, and the lengths of the postoperative intensive care unit and hospital stays were evaluated. Propensity score matching analysis was performed to reduce the influence of possible confounding variables and adjust for intergroup differences between the RRP and RALP groups.After performing 1:1 propensity score matching, the RRP and RALP groups included 307 patients, respectively. The operation time and anesthesia time in RALP were significantly longer than in the RRP group (both P < 0.001). However, the estimated blood loss and amount of administered fluids in RALP were significantly lower than in RRP (both P < 0.001). Also, RALP demonstrated a significantly lower incidence of transfusion and smaller amount of transfused packed red blood cells than RRP (both P < 0.001). Importantly, the incidence of AKI in RALP was significantly lower than in RRP (5.5% vs 10.4%; P = 0.044). Furthermore, the length of hospital stay in RALP was also significantly shorter (P < 0.001).The incidence of AKI after RALP is significantly lower than after RRP. RALP can therefore be a better surgical option than RRP in terms of decreasing the frequency of postoperative AKI. PMID- 26844487 TI - Is There Any Significant Difference in Stent Thrombosis Between Sirolimus and Paclitaxel Eluting Stents?: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. AB - Several meta-analyses have shown no significant difference in stent thrombosis (ST) between sirolimus eluting stents (SES) and paclitaxel eluting stents (PES). However, other meta-analyses have found SES to be superior to PES. Therefore, to solve this issue, we aim to compare the clinical outcomes between SES and PES during a follow-up period of about 1 or more years.We have searched Medline and EMBASE for randomized controlled trials (RCTs) comparing SES with PES. These RCTs have been carefully analyzed and then different types of ST including ST defined by the Academic Research Consortium (ARC), acute ST, late and very late ST have all been considered as the clinical endpoints in this study. A follow-up period of about 1 year, between 1 and 2 years as well as a longer follow-up period between 1 and 5 years have been considered. Data were retrieved and combined by means of a fixed-effect model because of a lower heterogeneity observed among the results. Odd ratios (OR) and 95% confidence intervals (CIs) were calculated and the pooled analyses were performed with RevMan 5.3 software.Twenty-nine studies from 19 RCTs comprising of 16,724 patients (8115 patients in the SES group and 8609 patients in the PES group) satisfied the inclusion criteria and were included in this meta-analysis. No significant differences in ST have been observed between SES and PES. Results were as follow: definite ST with OR: 0.87; 95% CI: 0.64-1.18, P = 0.36; probable ST with OR:0.72; 95% CI: 0.42-1.21, P = 0.21; definite, probable and/or possible ST with OR: 0.94; 95% CI: 0.75-1.17, P = 0.57; acute ST with OR: 0.99; 95% CI: 0.38-2.56, P = 0.98; subacute ST with OR: 0.72; 95% CI: 0.41-1.25, P = 0.25; early ST with OR: 0.81; 95% CI: 0.53-1.25, P = 0.34; late ST with OR: 0.72; 95% CI: 0.39-1.34, P = 0.30; very late ST with OR: 1.02; 95% CI: 0.72-1.44, P = 0.92; and any ST with OR: 0.86; 95% CI: 0.69-1.07, P = 0.18. Long-term ST between 1 and 5 years with OR: 0.93; 95% CI: 0.71-1.22, P = 0.60 was also not significantly different.No significant difference in ST has been observed between patients treated with either SES or PES. Hence SES and PES can both be considered almost equally effective. PMID- 26844488 TI - Prognostic Value of Cardiovascular Disease Risk Factors Measured in the First Trimester on the Severity of Preeclampsia. AB - Recent studies have suggested that preeclampsia and cardiovascular disease may share common mechanisms. The purpose of this prospective nested case-controlled study was to characterize a variety of cardiovascular disease risk factors measured during the first trimester of pregnancy in predicting subsequent outcomes and the severity of preeclampsia.We ascertained the severity of preeclampsia at the onset of the disease, and the presence of intrauterine growth restriction (IUGR). We compared first trimester maternal serum cardiovascular disease risk factors in preeclampsia subjects versus normal pregnancies, early onset versus late-onset preeclampsia, and preeclampsia with IUGR versus without IUGR. To identify the prognostic value of independent predictors on the severity of preeclampsia, we calculated the area under the receiver operating characteristics curve (AUC) using logistic regression analysis.There were 134 cases of preeclampsia and 150 uncomplicated pregnancies, and preeclampsia cases were classified as early-onset (53 cases) or late-onset (81 cases), or as with IUGR (44 cases) or without IUGR (90 cases). Among the cardiovascular disease risk factors, maternal serum high-sensitive C-reactive protein (hsCRP) and homocysteine were predictors of both early-onset preeclampsia and preeclampsia with IUGR. For the detection of early onset preeclampsia or preeclampsia with IUGR, the AUC for the combination model (0.943 and 0.952, respectively) was significantly higher than with serum hsCRP or serum homocysteine only.Patients with preeclampsia can be subdivided into different severities according to time of onset and fetal weight. Cardiovascular risk factors distinguish a subgroup of these patients. PMID- 26844489 TI - Role of Educational Status in Explaining the Association between Body Mass Index and Cognitive Function. AB - Preserving physical and cognitive function becomes an important issue as people age. A growing number of studies have found that the correlation between body mass index (BMI) and cognitive function changes in different age groups. It is obvious that higher educational status is linked to higher cognitive function in terms of numerous risk factors that influence cognitive function. This study aimed to investigate the interplay between obesity and cognitive function categorized by different educational status.This study included 5021 participants aged 20 to 59 years who completed 3 neurocognitive function tests, including a simple reaction time test (SRTT), a symbol digit substitution test (SDST), and a serial digit learning test (SDLT) as reported in the National Health and Nutrition Examination Survey (NHANES) III database. The associations between neurocognitive function and BMI were analyzed using multivariate linear regression while controlling for confounders.After adjusting for pertinent covariates in mode 3, the beta coefficients in the female participants with more than 12 years of education (interpreted as change of 3 neurocognitive function tests for each increment in BMI) comparing obesity groups to those with normal BMI were 16.2 (P < 0.001 for SRTT), 0.14 (P < 0.05 for SDST), and 0.9 (P < 0.05 for SDLT). Male participants with more than 12 years of education and female participants with fewer than 12 years of education demonstrated increased impairment as their BMI increased. However, this association was not significant after adjustments.Obese individuals had worse neurocognitive function than those of normal weight or overweight, especially in women with a high educational level. PMID- 26844490 TI - Mutation Changes in the preC/Core Promoter in HBeAg-Positive Patients With Chronic Hepatitis B During Interferon Therapy. AB - To study the changes in 3 mutations related with hepatitis B e antigen (HBeAg) in patients with HBeAg-positive chronic hepatitis B (CHB) during interferon therapy.HBeAg seroconversion is a major therapeutic milestone for patients with HBeAg-positive CHB. The precore mutation G1896A and the basal core promoter mutations A1762T/G1764A are 3 important mutations that affect the expression of HBeAg; however, the change of these 3 mutations in CHB patients during interferon therapy has not yet been evaluated.Sixty-four treatment-naive patients with HBeAg positive CHB were treated with interferon for 48 weeks and followed up for 24 weeks. Serum samples were collected from all of the participants at different time points and then subjected to viral DNA extraction. The precore and basal core promoter sequences were determined using nested PCR and direct sequencing. The treatment outcomes were confirmed both at the end of therapy and the follow up period, and the results were compared between patients with mutant and wild type virus.No significant difference in HBeAg loss and HBeAg seroconversion was observed between patients with mutant versus wild-type virus although the portion of patients who achieved HBeAg loss/seroconversion with mutant virus was a little higher than in patients with wild-type virus. Once a mutation exists, it is not replaced with the wild-type sequence during interferon therapy and follow-up; moreover, our results show that mutants stably coexist with the wild-type virus during interferon therapy.This study shows the changes in 3 mutations affecting the expression of HBeAg during interferon therapy. However, additional studies with a larger sample size and more sensitive detection methods are needed to uncover the underlying mechanism and clinical significance of these results. PMID- 26844491 TI - Clinical Uses of Probiotics. AB - Probiotics are live nonpathogenic microorganisms. Many of these microorganisms are part of the normal human gut flora, where they live in a symbiotic relationship. Probiotics have been used to treat gastrointestinal (GI) and non-GI medical conditions. However, the data supporting their use are often conflicting, especially for non-GI-associated illnesses. The strongest evidence supporting the use of probiotics is related to the treatment of acute diarrhea and pouchitis. Atopic eczema in children and genitourinary infections are the only non-GI related medical conditions where probiotics may have some beneficial effects. Product selection and dosing are not the same in all conditions, and the beneficial effects of each probiotic strain cannot be generalized.The purpose of this article is to provide most recent information about probiotics and its uses. In contrast with previously published reviews on probiotics, we also discuss the composition of various products (Table 1), indications for their use (Table 2), product selection, and dosing of probiotics.Probiotics are safe and appear to exert some beneficial effects in GI-related illnesses. The use of probiotics in non-GI illnesses is not sufficiently supported by current data. PMID- 26844492 TI - Incidence and Risks of Congenital Anomalies of Kidney and Urinary Tract in Newborns: A Population-Based Case-Control Study in Taiwan. AB - Congenital anomalies of the kidney and urinary tract (CAKUT) are 1 of the major factors in young adults needing renal replacement therapy, but there is little extensive assessment of their incidence and risk factors. This study aimed to evaluate trends in the incidence of and risk factors for CAKUT among all births in Taiwan.This population-based case-control study design was conducted using the Taiwan national births registry, which contains detailed information about maternal health and characteristics of newborns, supplied by health professionals. Of 1,603,794 newborns registered between 2004 and 2014, 668 infants were reported to have CAKUT. Newborns without congenital anomalies were matched with CAKUT cases by birth year, month, and Apgar score in a ratio of 5:1. Odds ratio (OR) and 95% confidence interval (CI) for developing CAKUT were calculated using a conditional multivariate logistic regression model.The incidence of CAKUT was approximately 4.2 per 10,000 births. The adjusted ORs for CAKUT in newborns associated with maternal age of 20 to 29 (OR, 2.18; 95% CI, 1.11-4.28), or 30 to 39 (OR, 2.29; 95% CI, 1.17-4.51), maternal gestational diabetes (OR, 2.22, 95% CI, 1.06-4.67), maternal thalassemia/hemochromatosis (OR, 2.67; 95% CI, 1.35-5.27), polyhydramnios or oligohydramnios (OR, 9.16; 95% CI, 5.46-15.37), birth parity >1 (OR, 0.27; 95% CI, 0.15-0.50), having a gestational age <37 weeks (OR, 1.48; 95% CI, 1.23-1.78), and being a boy (OR, 1.83; 95% CI, 1.53-2.19). Infants of mother with gestational diabetes were more likely to have congenital anomalies, small gestational age (<37 weeks) and low birth weight.CAKUT are associated with several maternal health risk factors. As Taiwan has the highest prevalence and incidence rates of end-stage renal disease in the world, these findings strongly support the need to develop professional guidelines for prenatal counseling and management of women at risk of adverse birth outcomes, to prevent kidney disease progression and reduce complications. PMID- 26844493 TI - Combination Antiretroviral Therapy Is Associated With Reduction in Liver Fibrosis Scores in HIV-1-Infected Subjects. AB - HIV increases the risk of liver disease as do two common coinfections, hepatitis B and C viruses (HBV and HCV). However, whether combination antiretroviral therapy (cART) reverses or exacerbates hepatic fibrosis remains unclear.This was an observational retrospective study. cART-naive HIV-infected subjects without a history of substance abuse (including alcohol) had liver disease stage determined by aspartate aminotransferase-to-platelet ratio indices (APRIs) and fibrosis-4 (FIB-4) before and 24 and 48 weeks after cART. All the data were retrieved from previously established cohorts. Values before and after cART were compared using Wilcoxon test for paired samples. Regression analyses were used to determine factors associated with moderate-to-severe liver disease.Of the 1105 HIV-infected subjects, 120 were HBV coinfected and 64 were HCV coinfected. About 20% of HIV monoinfected participants had APRI and FIB-4 scores consistent with moderate-to significant fibrosis compared to ~36% of HIV-HBV coinfected and 67% to 77% of HIV HCV coinfected participants. In adjusted analyses compared with HIV monoinfection, HBV coinfection was associated with 1.18-fold higher APRI (P < 0.001) and a 1.12-fold higher FIB-4 (P = 0.007) prior to cART; while HCV coinfection was associated with 1.94-fold higher APRI (P < 0.001) and a 1.43-fold higher FIB-4 (P < 0.001). After 48 weeks of cART, both fibrosis scores decreased in all subjects; however, HCV coinfection was still associated with higher fibrosis scores at week 48 compared to HIV monoinfection.cART was associated with improvement in hepatic fibrosis scores in the majority of HIV-hepatitis coinfected and HIV-monoinfected Chinese participants. PMID- 26844494 TI - Serum Levels of Follistatin Are Positively Associated With Serum-Free Thyroxine Levels in Patients With Hyperthyroidism or Euthyroidism. AB - Follistatin is a glycoprotein with various biologic functions that plays a role in adipocyte differentiation, muscle stimulation, anti-inflammation, and energy homeostasis. Thyroid hormones influence energy expenditure, glucose, and lipid metabolism. The association between serum follistatin level and thyroid function statuses has seldom been evaluated.The objectives of this study were to compare serum follistatin concentrations in different thyroid function statuses and to evaluate the associations between serum follistatin and free thyroxine (fT4) levels.In this study, 30 patients with hyperthyroidism (HY group) and 30 euthyroid individuals (EU group) were recruited. The patients of HY group were treated with antithyroid regimens as clinically indicated, whereas no medication was given to EU group. The demographic and anthropometric characteristics, biochemical data, serum levels of follistatin, and thyroid function of both groups at baseline and at the 6th month were compared. Data of all patients were pooled for the analysis of the associations between the levels of follistatin and fT4.At baseline, the HY group had significantly higher serum follistatin levels than the EU group (median [Q1, Q3]: 1.81 [1.33, 2.78] vs 1.13 [0.39, 1.45] ng/mL, P < 0.001). When treated with antithyroid regimens, the follistatin serum levels in HY group decreased to 1.54 [1.00, 1.88] ng/mL at the 6th month. In all patients, the serum levels of follistatin were positively associated with fT4 levels at baseline (beta = 0.54, P = 0.005) and at the 6th month (beta = 0.59, P < 0.001). The association between follistatin and fT4 levels remained significant in the stepwise multivariate regression analysis, both initially and at the 6th month.In comparison to the EU group, patients with hyperthyroidism had higher serum follistatin levels, which decreased after receiving antithyroid treatment. In addition, the serum follistatin concentrations were positively associated with serum fT4 levels in patients with hyperthyroidism or euthyroidism. PMID- 26844495 TI - CT Imaging Biomarkers Predict Clinical Outcomes After Pancreatic Cancer Surgery. AB - This study aimed to determine whether changes in contrast-enhanced computed tomography (CT) parameters could predict postsurgery overall and progression-free survival (PFS) in pancreatic cancer patients. Seventy-nine patients with a final pathological diagnosis of pancreatic adenocarcinoma were included in this study from June 2008 to August 2012. Dynamic contrast-enhanced (DCE) CT of tumors was obtained before curative-intent surgery. Absolute enhancement change (AEC) and relative enhancement change (REC) were evaluated on DCE-CT. PFS and overall survival (OS) were compared based on CT enhancement patterns. The markers of fibrogenic alpha-smooth muscle antigen (alpha-SMA) and periostin in tumor specimens were evaluated by immunohistochemical staining. The chi test was performed to determine whether CT enhancement patterns were associated with alpha SMA-periostin expression levels (recorded as positive or negative). Lower REC (<0.9) was associated with shorter PFS (HR 0.51, 95% CI: 0.31-0.89) and OS (HR 0.44, 95% CI: 0.25-0.78). The alpha-SMA and periostin expression level were negatively correlated with REC (both P = 0). Among several CT enhancement parameters, REC was the best predictor of patient postsurgery survival. Low REC was associated with a short progression-free time and poor survival. The pathological studies suggested that REC might be a reflection of cancer fibrogenic potential. PMID- 26844496 TI - Adjuvant Cytokine-Induced Killer Cell Therapy Improves Disease-Free and Overall Survival in Solitary and Nonmicrovascular Invasive Hepatocellular Carcinoma After Curative Resection. AB - Cytokine-induced killer (CIK) cell therapy has recently been used as an adjuvant setting following resection of hepatocellular carcinoma (HCC), while its benefit remains unclear. This study aimed to evaluate the efficacy of adjuvant CIK application in solitary HCC patients undergoing curative resection with stratification of microvascular invasion (MVI).In total, specimens and data from 307 solitary HCC patients undergoing curative resection between January 2007 and December 2010 were included. Of these, 102 patients received CIK treatment after surgery (CIK group), whereas 205 patients did not (control group). Pathological evaluation was used to retrospectively determine MVI status. The CIK group had 60 MVI-negative and 42 MVI-positive patients, while the numbers in control group were 124 and 81. Kaplan-Meier and Cox regression analyses were used to validate possible effects of CIK treatment on disease free survival (DFS) and overall survival (OS) as appropriate.For all patients, the CIK group exhibited significantly higher OS than the control group (log-rank test; PDFS = 0.055, POS = 0.020). Further analysis based on MVI stratification showed that for patients with MVI, DFS and OS did not differ between the 2 groups (PDFS = 0.439, POS = 0.374). For patients without MVI, the CIK group exhibited better DFS and OS than the control group (PDFS = 0.042, POS = 0.007), and multivariate analyses demonstrated that CIK treatment was an independent prognostic factor both for DFS and OS.For solitary HCC, CIK cell therapy after curative resection improves DFS and OS for patients without MVI, but has no statistically significant survival benefit for patients with MVI. PMID- 26844497 TI - Vaginal Mucosal Homeostatic Response May Determine Pregnancy Outcome in Women With Bacterial Vaginosis: A Pilot Study. AB - Bacterial vaginosis (BV) is considered as a trigger for an inflammatory response that could promote adverse pregnancy outcome (APO). We hypothesized that BV related inflammation could be counterbalanced by anti-inflammatory and mucosal homeostatic responses that could participate in pregnancy outcomes.A total of 402 vaginal self-samples from pregnant women in their first trimester were screened by Nugent score. In this population, we enrolled 23 pregnant women with BV but without APO, 5 pregnant women with BV and developing APO, 21 pregnant women with intermediate flora, and 28 random control samples from pregnant women without BV or APO.BV without APO in pregnant women was associated with 28-fold interleukin 8, 5-fold interleukin-10, and 40-fold interleukin-22 increases in expression compared to controls. BV associated with APO in pregnant women shared 4-fold increase in tumor necrosis factor, 100-fold decrease in interleukin-10, and no variation in interleukin-22 expressions compared to controls. Next-generation sequencing of vaginal microbiota revealed a shift from obligate anaerobic bacteria dominance in BV without APO pregnant women to Lactobacillus dominance microbiota in BV with APO.Our results show that the anti-inflammatory and mucosal homeostatic responses to BV may determine outcome of pregnancy in the setting of BV possibly through effects on the vaginal microbiota. PMID- 26844498 TI - Sparing Sphincters and Laparoscopic Resection Improve Survival by Optimizing the Circumferential Resection Margin in Rectal Cancer Patients. AB - The goal of rectal cancer treatment is to minimize the local recurrence rate and extend the disease-free survival period and survival. For this aim, obtainment of negative circumferential radial margin (CRM) plays an important role. This study evaluated predictive factors for positive CRM status and its effect on patient survival in mid- and distal rectal tumors.Patients who underwent curative resection for rectal cancer were included. The main factors were demographic data, tumor location, surgical technique, neoadjuvant therapy, tumor diameter, tumor depth, lymph node metastasis, mesorectal integrity, CRM, the rate of local recurrence, distant metastasis, and overall and disease-free survival. Statistical analyses were performed by using the Chi-squared test, Fisher exact test, Student t test, Mann-Whitney U test and the Mantel-Cox log-rank sum test.A total of 420 patients were included, 232 (55%) of whom were male. We observed no significant differences in patient characteristics or surgical treatment between the patients who had positive CRM and who had negative CRM, but a higher positive CRM rate was observed in patients undergone abdominoperineal resection (APR) (P < 0.001). Advanced T-stage (P < 0.001), lymph node invasion (P = 0.001) and incomplete mesorectum (P = 0.007) were encountered significantly more often in patients with positive CRM status. Logistic regression analysis revealed that APR (P < 0.001) and open resection (P = 0.046) were independent predictors of positive CRM status. Moreover, positive CRM was associated with decreased 5-year overall and disease-free survival (P = 0.002 and P = 0.004, respectively).This large single-institution series demonstrated that APR and open resection were independent predictive factors for positive CRM status in rectal cancer. Positive CRM independently decreased the 5-year overall and disease-free survival rates. PMID- 26844499 TI - Vertebral Compression Fracture Related to Pancreatic Cancer With Osteoblastic Metastasis: A Case Report and Literature Review. AB - Compression fracture of the vertebral body is common in the older patients. The possible etiology like osteoporosis or cancer metastasis should be included as a possibility in the differential diagnosis for severe back pain, to prevent delays in diagnosis and treatment. More severe fractures can cause significant pain, leading to inability to perform activities of daily living, and life-threatening in the older patient.We report a rare case of a 61-year-old man suffering from severe lower back pain and intermittent abdominal fullness. He came to our clinic, where muscle power was normal, but could not stand up or change posture because of severe back pain. Plain film and magnetic resonance imaging of lumbar spine both revealed osteoblastic lesion at L2 spine. Abdomen computed tomography showed a mass at the pancreatic body. The pancreatic cancer with osteoblastic metastasis was diagnosed. After receiving multimodality therapy such as percutaneous vertebroplasty and pain controlling, we provided effective palliation of symptoms, aggressive rehabilitation program, and better quality of life.Our case highlights the benefits of multidisciplinary cancer treatment for such patient, preventing the complications such as immobilization accompanied with adverse effects like musculoskeletal, respiratory, and cardiovascular systems. All clinicians should be informed of the clinical findings to provide patients with suitable therapies and surveys. PMID- 26844500 TI - Invasive Haemophilus influenzae Serotype f Case Reports in Mazovia Province, Poland. AB - After successful introduction of anti-Haemophilus influenzae (Hi) serotype b vaccination program in Poland, invasive non-b or nontypeable H. influenzae infections have been reported more frequently alike in other countries all over the world. In this paper, we report 2 cases of H. influenzae serotype f (Hif) meningitis with severe clinical presentations which are rarely seen in previously healthy children.The first case is a 6-year-old girl who was admitted to pediatric ward with signs of meningitis. Laboratory tests confirmed bacteremic meningitis caused by Hif. The girl responded very well to administered treatment and recovered without any further complications. No underlying comorbidities were found. The second patient was a 4-year-old boy who, in course of Hif bacteremic meningitis, developed rapid septicemia and, despite aggressive treatment, died within a few hours of hospitalization. The child's past history was unremarkable.By presenting these cases, we would like to remind clinicians that invasive non-b Hi infections can become fatal not only in the group of the youngest children or children with coexisting comorbidities, as most commonly reported in the worldwide literature. At the same time, we want to emphasize the legitimacy of constant monitoring Hi epidemiology in order to take accurate actions if necessary. PMID- 26844501 TI - Associations of Matrix Metalloproteinase-9 and Tissue Inhibitory Factor-1 Polymorphisms With Parkinson Disease in Taiwan. AB - Matrix metalloproteinases (MMPs) function in the degradation of extracellular matrix and are considered to play a role in the pathogenesis of neurodegenerative diseases including Parkinson disease (PD). MMPs activities are modulated by tissue inhibitors of metalloproteinases (TIMPs). This study examined whether the genetic polymorphisms of MMP-3, gelatinase (MMP-2 and MMP-9), TIMP-2, and TIMP-1 were associated with PD in Taiwan.A total of 359 PD patients and 332 controls were enrolled. The candidate genetic variants included MMP-2 rs2285053 (-735 C > T), MMP-3 rs3025058 (-1171 5A > 6A), MMP-9 rs3918241 (-1831 T > A), rs17576 (G > A, R279Q), and rs3787268 (G > A, intron), TIMP-1 rs4898 (T > C, F124F), and TIMP 2 rs7503607 (-269 G > T). Associations were tested by logistic regression, adjusted with gender and age at onset.Minor allele frequency of TIMP-1 rs4898 (36.0%) was significantly lower in the male PD patients than in the male controls (51.2%) (chi test, P = 0.004). When adjusted with gender and age at onset, MMP-9 rs17576 AA genotype was associated with PD susceptibility in a recessive fashion (odds ratios [OR] = 2.28, 95% confidence intervals [95% CI] = 1.12-4.62, P = 0.02). In males, TIMP-1 rs4898 C allele was associated with a protective effect on PD (OR = 0.75, 95% CI = 0.60-0.94, P = 0.014). We did not find association between the examined genetic variants of MMP-2, MMP-3, and TIMP-2 and PD susceptibility.This is the first study that demonstrated a protective effect of TIMP-1 rs4898 C allele on male PD and a modest association of MMP-9 rs17576 AA genotype with PD susceptibility in the Taiwan population. Further replication is needed for confirmation. PMID- 26844502 TI - Epstein-Barr Virus-Positive T/NK-Cell Lymphoproliferative Disorders Manifested as Gastrointestinal Perforations and Skin Lesions: A Case Report. AB - Systemic Epstein-Barr virus (EBV)-positive T-cell lymphoproliferative disorders (LPDs) of childhood is a highly aggressive EBV-positive T/natural killer (NK) cell LPD, which emerges in the background of chronic active EBV infection (CAEBV) or shortly after primary acute EBV infection. The clinical presentations of CAEBV are varied; patients with atypical manifestations are easily misdiagnosed. We described a 14-year-old boy suffering from digestive disorders and intermittent fever for 1 year and 9 months, whose conditions worsened and skin lesions occurred 2 months before hospitalization. He was diagnosed as inflammatory bowel diseases (IBD) and treated accordingly. His other clinical features, hepatosplenomegaly, lymphadenopathy, anemia, hypoalbuminemia, and elevated inflammatory marks, were found in hospitalization. The boy suffered from repeatedly spontaneous intestinal perforations shortly after hospitalization and died of intestinal hemorrhea. The pathological results of intestine and skin both showed EBV-positive T/NK-cell LPD (lymphoma stage).There are rare studies reporting gastrointestinal perforations in EBV-positive T/NK-cell LPD, let alone repeatedly spontaneous perforations. Based on the clinical features and pathological results of this patient, the disease progressed from CAEBV (T-cell type) to systemic EBV-positive T-cell LPD of childhood (lymphoma). Not all the patients with CAEBV could have unusual patterns of anti-EBV antibodies. However, the presence of high EBV loads (EBV-encoded early small ribonucleic acid (RNA) (EBER) in affected tissues and/or EBV deoxyribonucleic acid (DNA) in peripheral blood) is essential for diagnosing CAEBV. Maybe because of his less common clinical features for CAEBV and negative anti-EBV antibodies, the boy was not diagnosed correctly. We should have emphasized the test for EBER or EBV-DNA. Meanwhile, for the IBD patients whose manifestations were not typical, and whose conditions were not improved by suitable therapies against IBD, infectious and malignant diseases should be considered. PMID- 26844503 TI - Recent Trends in Hospitalization for Acute Myocardial Infarction in Beijing: Increasing Overall Burden and a Transition From ST-Segment Elevation to Non-ST Segment Elevation Myocardial Infarction in a Population-Based Study. AB - Comparable data on trends of hospitalization rates for ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) remain unavailable in representative Asian populations.To examine the temporal trends of hospitalization for acute myocardial infarction (AMI) and its subtypes in Beijing.Patients hospitalized for AMI in Beijing from January 1, 2007 to December 31, 2012 were identified from the validated Hospital Discharge Information System. Trends in hospitalization rates, in-hospital mortality, length of stay (LOS), and hospitalization costs were analyzed by regression models for total AMI and for STEMI and NSTEMI separately. In total, 77,943 patients were admitted for AMI in Beijing during the 6 years, among whom 67.5% were males and 62.4% had STEMI. During the period, the rate of AMI hospitalization per 100,000 population increased by 31.2% (from 55.8 to 73.3 per 100,000 population) after age standardization, with a slight decrease in STEMI but a 3-fold increase in NSTEMI. The ratio of STEMI to NSTEMI decreased dramatically from 6.5:1.0 to 1.3:1.0. The age-standardized in-hospital mortality decreased from 11.2% to 8.6%, with a significant decreasing trend evident for STEMI in males and females (P < 0.001) and for NSTEMI in males (P = 0.02). The rate of percutaneous coronary intervention increased from 28.7% to 55.6% among STEMI patients. The total cost for AMI hospitalization increased by 56.8% after adjusting for inflation, although the LOS decreased by 1 day.The hospitalization burden for AMI has been increasing in Beijing with a transition from STEMI to NSTEMI. Diverse temporal trends in AMI subtypes from the unselected "real-world" data in Beijing may help to guide the management of AMI in China and other developing countries. PMID- 26844504 TI - Contribution of Hepatitis B to Long-Term Outcome Among Patients With Acute Myocardial Infarction: A Nationwide Study. AB - Although a possible association between hepatitis B and cardiovascular disease has been identified, the impact of viral hepatitis B on long-term prognosis after an acute myocardial infarction (AMI) is uncertain. Therefore, the aim of our study was to evaluate the specific impact of viral hepatitis B on survival after a first AMI through a retrospective analysis of data from the Taiwan National Health Insurance Research Database.This was a nationwide, propensity score matched case-control study of patients admitted to hospitals between January 2000 and December 2012 with a primary diagnosis of a first AMI. Among the 7671 prospective patients, 244 patients with a confirmed diagnosis of viral hepatitis B infection were identified. A propensity score, one-to-one matching technique was used to match 244 controls to the AMI group for analysis. Controls were matched on the following variables: sex, age, hypertension, dyslipidemia, diabetes, peripheral vascular disease, heart failure, cerebrovascular accidents, end-stage renal disease, chronic obstructive pulmonary disease, and percutaneous coronary intervention (PCI).Overall, viral hepatitis B infection did not influence the 12-year survival rate (P = 0.98). However, survival was lower in female patients with viral hepatitis B infection compared to those without (P = 0.03; hazard ratio, 1.79; 95% confidence interval, 1.08-2.94). Inclusion of percutaneous coronary management improved survival, independent of sex, age, or hepatitis B status.Hepatitis B infection might increase the mortality risk of female patients after a first AMI. PCI may improve the long-term survival of patients after a first AMI, regardless of sex, age, and hepatitis B status. PMID- 26844505 TI - Efficacy and Safety of Bisphosphonates for Low Bone Mineral Density After Kidney Transplantation: A Meta-Analysis. AB - In patients with low bone mineral density (BMD) after kidney transplantation, the role of bisphosphonates remains unclear. We performed a systematic review and meta-analysis to investigate the efficacy and safety of bisphosphonates.We retrieved trials from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception through May 2015. Only randomized controlled trials that compared bisphosphonate-treated and control groups of patients with low bone mineral density after kidney transplantation were included. The primary outcomes were the percent change in BMD, the absolute change in BMD, and the BMD at the end of study at the lumbar spine. The results were expressed as the mean difference (MD) or relative risk (RR) with the 95% confidence interval (CI). We used a random-effects model to pool the outcomes.We included 17 randomized controlled trials with 1067 patients. Only 1 included trial was found to be at low risk of bias. The rest of the included studies were found to have high to uncertain risk of bias. Compared with the control group, those who received bisphosphonates had a significant increase in percent change in BMD (mean difference [MD] = 5.51, 95% confidence interval [CI] 3.22-7.79, P < 0.00001) and absolute change in BMD (MD = 0.05, 95% CI 0.04-0.05, P < 0.00001), but a nonsignificant increase in BMD at the end of the study (MD = 0.02, 95% CI 0.01 to 0.05, P = 0.25) at the lumbar spine. Bisphosphonates resulted in a significant improvement in percent change in BMD (MD = 4.95, 95% CI 2.57-7.33, P < 0.0001), but a nonsignificant improvement in absolute change in BMD (MD = 0.03, 95% CI -0.00 to 0.06, P = 0.07) and BMD at the end of the study (MD = -0.01, 95% CI -0.04 to 0.02, P = 0.40) at the femoral neck. No significant differences were found in vertebral fractures, nonvertebral fractures, adverse events, and gastrointestinal adverse events.Bisphosphonates appear to have a beneficial effect on BMD at the lumbar spine and do not significantly decrease fracture events in recipients. However, the results should be interpreted cautiously due to the lack of robustness and the heterogeneity among studies. PMID- 26844506 TI - Magnetic Resonance Imaging of Patients With Chronic Lateral Epicondylitis: Is There a Relationship Between Magnetic Resonance Imaging Abnormalities of the Common Extensor Tendon and the Patient's Clinical Symptom? AB - The aim of the study is to determine the inter-reliability and intra-observer reliability of magnetic resonance imaging (MRI) for lateral epicondylitis and investigate whether there is a potential relationship between MRI abnormalities of the common extensor tendon (CET) and its clinical symptom.The study group comprised 96 consecutive patients (46 men and 50 women) with a clinical diagnosis of chronic lateral epicondylitis, which were examined on 3.0 T MR. An MRI scoring system was used to grade the degree of tendinopahty. Three independent musculoskeletal radiologists, who were blinded to the patients' clinical information, scored images separately. Clinical symptoms were assessed using the Patient-Rated Tennis Elbow Evaluation (PRTEE).Of all the patients, total 96 elbows had MRI-assessed tendinopathy, including 38 (39.6%) with grade 1, 31 (32.3%) with grade 2, and 27 (28.1%) with grade 3. Inter-observer reliability and intra-observer agreement for MRI interpretation of the grades of tendinopathy was good, and a positive correlation between the grades of tendinopathy and PRTEE was determined.MRI is a reliable tool in determining radiological severity of chronical lateral epicondylitis. The severity of MR signal changes positively correlate with the patient's clinical symptom. PMID- 26844507 TI - Pregnancy Outcome After I-131 Therapy for Patients With Thyroid Cancer: A Nationwide Population-Based Cohort Study. AB - The aim of this study was to evaluate the influence of I-131 therapy on pregnancy outcome in patients that received therapeutic I-131 doses for thyroid cancer in Taiwan.This nationwide population-based cohort study was based on data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database. We identified 11,708 women with thyroid cancer (>= 15 and <= 50 years of age) by International Classification of Diseases, Ninth Revision, Clinical Modification codes. Patients were divided into 2 cohorts: I-131 therapy cohort and non-I-131 therapy cohort. The mean follow-up period was 6.08 years for the I-131 cohort and 6.87 years for the non-I-131 cohort. The case cohort and the control cohort comprised 775 and 716 pregnant patients, respectively.The overall incidence of pregnancy was significantly lower in the I-131 cohort (adjusted HR = 0.77, 95% CI = 0.70-0.86) and it was also observed when the patients were stratified according to age (HR = 0.73, 95% CI = 0.64-0.83 in 25-34 years; HR = 0.63, 95% CI = 0.49 0.82 in 35-44 years). Patients in the I-131 cohort had a lower successful delivery rate, particularly among patients in 25 to 34 years (OR = 0.60, 95% CI = 0.45-0.80). No significant difference was observed for adverse pregnancy conditions between 2 cohorts.I-131 therapy is associated with decreased pregnancy and successful delivery rates. The underlying mechanism likely involves physician recommendation, patient's psychological issue, and potential impact of I-131 treatment on reproductive health. Further investigation is needed. PMID- 26844508 TI - A Systematic Review and Meta-Analysis of the Relationship Between Hospital Volume and the Outcomes of Percutaneous Coronary Intervention. AB - Previous reviews have suggested that hospital volume is inversely related to in hospital mortality. However, percutaneous coronary intervention (PCI) practices have changed substantially in recent years, and whether this relationship persists remains controversial.A systematic search was performed using PubMed, Embase, and the Cochrane Library to identify studies that describe the effect of hospital volume on the outcomes of PCI. Critical appraisals of the methodological quality and the risk of bias were conducted independently by 2 authors. Fourteen of 96 potentiality relevant articles were included in the analysis. Twelve of the articles described the relationship between hospital volume and mortality and included data regarding odds ratios (ORs); 3 studies described the relationship between hospital volume and long-term survival, and only 1 study included data regarding hazard ratios (HRs). A meta-analysis of postoperative mortality was performed using a random effects model, and the pooled effect estimate was significantly in favor of high volume providers (OR: 0.79; 95% confidence interval [CI], 0.72-0.86; P < 0.001). A systematic review of long-term survival was performed, and a trend toward better long-term survival in high volume hospitals was observed.This meta-analysis only included studies published after 2006 and revealed that postoperative mortality following PCI correlates significantly and inversely with hospital volume. However, the magnitude of the effect of volume on long-term survival is difficult to assess. Additional research is necessary to confirm our findings and to elucidate the mechanism underlying the volume-outcome relationship. PMID- 26844509 TI - Optimal Cut-Off Values of Lymph Node Ratio Predicting Recurrence in Papillary Thyroid Cancer. AB - Regional lymph node (LN) metastasis has a significant impact for prediction of recurrence in patients with papillary thyroid cancers (PTC); however, the prognostic value of the lymph node ratio (LNR), which is defined as the ratio of the number of metastatic LNs to the total number of investigated LNs, is controversial. In this study, we determined the optimal cut-off values of LNRs for the prediction of recurrence in PTC patients.This large cohort study retrospectively evaluated 2294 patients who had undergone total thyroidectomy for PTC at a single institution from October 1985 to June 2009. The prediction probability of central LNR (cLNR, level VI) and total LNR (tLNR, levels II-VI) were estimated by binominal logistic regression analysis. Hazard ratios of the cut-off LNR values for cancer recurrence were calculated for relevant covariates using multivariate Cox regression analyses. Kaplan-Meier analyses were also utilized to assess the effects of estimated LNR cut-off values on recurrence-free survival (RFS).Of the 2294 patients, 138 (6.0%) presented cancer recurrence during the follow-up period (median duration = 107.1 months). The prediction probability indicated that LNRs of 0.4 and 0.5 for central LN and total LN, respectively, are optimal cut-off values for precise prediction with minimization of outliers. Multivariate Cox regression analyses revealed that cLNR >=0.4 was independently predictive of recurrence in patients with N0 and N1a PTCs (hazard ratio [HR]: 7.016, 95% confidence interval [CI]: 3.72-12.986, P < 0.001) and that tLNR >=0.5 indicated a significantly increased risk of recurrence in patients with N1b PTCs (HR: 2.372, 95% CI: 1.458-3.860, P < 0.001). In addition, Kaplan Meier analyses clearly demonstrated that these LNR cut-off values are precisely operational in RFS estimation.The cut-off LNR values of 0.4 and 0.5 for cLNR and tLNR, respectively, were identified. Risk stratification combined with these LNR cut-off values may prove useful to determine treatment and follow-up strategies for PTC patients. PMID- 26844510 TI - A Case Report of Locked-in Syndrome Due to Bilateral Vertebral Artery Dissection After Cervical Spine Manipulation Treated by Arterial Embolectomy. AB - Cervical spine manipulation (CSM) is a commonly spinal manipulative therapies for the relief of cervical spine-related conditions worldwide, but its use remains controversial. CSM may carry the potential for serious neurovascular complications, primarily due to vertebral artery dissection (VAD) and subsequent vertebrobasilar stroke. Here, we reported a rare case of locked-in syndrome (LIS) due to bilaterial VAD after CSM treated by arterial embolectomy.A 36-year-old right-handed man was admitted to our hospital with numbness and weakness of limbs after treating with CSM for neck for half an hour. Gradually, although the patient remained conscious, he could not speak but could communicate with the surrounding by blinking or moving his eyes, and turned to complete quadriplegia, complete facial and bulbar palsy, dyspnea at 4 hours after admission. He was diagnosed with LIS. Then, the patient was received cervical and brain computed tomography angiography that showed bilateral VAD. Aortocranial digital subtraction angiography showed vertebrobasilar thrombosis, blocking left vertebral artery, and stenosis of right vertebral artery. The patient was treated by using emergency arterial embolectomy and followed by antiplatelet therapy and supportive therapy in the intensive care unit and a general ward. Twenty-seven days later, the patient's physical function gradually improved and discharged but still left neurological deficit with muscle strength grade 3/5 and hyperreflexia of limbs.Our findings suggested that CSM might have potential severe side-effect like LIS due to bilaterial VAD, and arterial embolectomy is an important treatment choice. The practitioner must be aware of this complication and should give the patients informed consent to CSM, although not all stroke cases temporally related to SCM have pre-existing craniocervical artery dissection. PMID- 26844511 TI - Predictive Mortality Index for Community-Dwelling Elderly Koreans. AB - There are very few predictive indexes for long-term mortality among community dwelling elderly Asian individuals, despite its importance, given the rapid and continuous increase in this population. We aimed to develop 10-year predictive mortality indexes for community-dwelling elderly Korean men and women based on routinely collected clinical data.We used data from 2244 elderly individuals (older than 60 years of age) from the southwest Seoul Study, a prospective cohort study, for the development of a prognostic index. An independent longitudinal cohort of 679 elderly participants was selected from the Korean Genome Epidemiology Study in Ansan City for validation.During a 10-year follow-up, 393 participants (17.5%) from the development cohort died. Nine risk factors were identified and weighed in the Cox proportional regression model to create a point scoring system: age, male sex, smoking, diabetes, systolic blood pressure, triglyceride, total cholesterol, white blood cell count, and hemoglobin. In the development cohort, the 10-year mortality risk was 6.6%, 14.8%, 18.2%, and 38.4% among subjects with 1 to 4, 5 to 7, 8 to 9, and >=10 points, respectively. In the validation cohort, the 10-year mortality risk was 5.2%, 12.0%, 16.0%, and 16.0% according to these categories. The C-statistic for the point system was 0.73 and 0.67 in the development and validation cohorts, respectively.The present study provides valuable information for prognosis among elderly Koreans and may guide individualized approaches for appropriate care in a rapidly aging society. PMID- 26844512 TI - Circulating MicroRNA223 is a New Biomarker for Inflammatory Bowel Disease. AB - Endoscopy is an important tool in screening and monitoring inflammatory bowel disease (IBD); however, it is invasive, costly, and associated with risks to the patients. Recently, circulating microRNAs (miRNAs) have emerged as promising noninvasive biomarkers. We proposed that the expression of serum microRNA223 (miR 223) could be a biomarker for IBD.Studies were conducted using serum samples from 100 patients with IBD (50 with Crohn's disease [CD] and 50 with ulcerative colitis [UC]) and 50 healthy controls. The expression of serum miR-223 was measured by quantitative reverse transcription-polymerase chain reaction. The clinical disease activity was assessed by measurement of the Crohn's disease activity index for CD and the Mayo score for UC. Endoscopies were performed and graded according to the simple endoscopic score for CD and the ulcerative colitis endoscopic index of severity scores for UC. Blood samples for the measurement of high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were taken within 1 week before or after endoscopy.Serum miR-223 expression increased 2.2 times in patients with CD and 2.8 times in patients with UC compared with the control group. Most importantly, the level of serum miR-223 was correlated with several indicators of disease activity both in CD and UC. Serum miR-223 demonstrated a higher Spearman r value than ESR and hs-CRP in detecting the disease activity of patients with IBD.Serum miR-223 might be a promising biomarker for monitoring disease activity in IBD patients. PMID- 26844513 TI - Forensic Pathological Study of 1656 Cases of Sudden Cardiac Death in Southern China. AB - Sudden cardiac death (SCD) is progressively threatening the lives of young people throughout the world. We conducted a retrospective study of SCD cases identified among sudden death cases based on comprehensive autopsies and pathological examinations in the Center for Medicolegal Expertise of Sun Yat-Sen University to investigate the exact etiological distribution and epidemiological features of SCD. One thousand six hundred fifty-six cases were identified, and SCD accounted for 43.0% of these sudden death cases. The mean age of the SCD cases-where the data of definite ages were accessible-was 38.2 years, and the highest incidence occurred among the 31- to 40-year-old cases (25.6%). The male-to-female ratio among SCD cases was 4.3:1, and this ratio peaked in the 41- to 50-year-old group (7.7:1). The places of death were confirmed in 1411 cases, and predominantly in hospitals (46.3%) and at home (33.8%). SCD occurred throughout the year with a marginally increase in April and May. The major causes of SCD were coronary atherosclerotic disease (CAD, 41.6%), unexplained sudden death (15.1%), and myocarditis (11.8%). Our data indicated that in the age group of younger affected persons (below 35 years old), sudden unexplained death and myocarditis were much more prevalent than CAD. According to anatomical examinations of the CAD-related SCD cases, the proportion of cases with coronary artery stenosis exceeding 75% (grade IV) was 67.2%. Moreover, the percentages of higher grades of coronary atherosclerosis increased with age. Among all branches of the coronary arteries, the left anterior descending branch was the most prone to atherosclerosis; atherosclerosis was present in this branch in 95.4% of the cases with atherosclerosis. Additionally, lesions of multiple branches of the coronary artery were associated with ageing. This is the first study to report the causes of death and basic epidemiological data related to SCD in Southern China. PMID- 26844514 TI - Influence of Whole-Body Vibration Training Without Visual Feedback on Balance and Lower-Extremity Muscle Strength of the Elderly: A Randomized Controlled Trial. AB - The purpose of this study was to investigate the influence of whole-body vibration (WBV) training without visual feedback on balance and lower-extremity muscle strength in the elderly.Elderly subjects who did not exercise regularly participated in this study. Subjects were randomly divided into a WBV with eyes open group, a visual feedback-deprived plus WBV (VFDWBV) group, and a control group (0 Hz, eyes open). WBV training was provided over a 3-month period, 3 times per week for 5 min each session. Balance performance was measured with the limits of stability test, and muscle strength was measured with an isokinetic dynamometer.A total of 45 elderly subjects with an average age of 69.22 +/- 3.97 years, divided into a WBV group (n = 14), a VFDWBV group (n = 17), and a control group (n = 14), completed the trial. Statistically significant differences were found in the balance performance of the 3 groups at different time points (time * group interaction: F = 13.213, P < 0.001), and the VFDWBV group had more improvement in balance than the WBV and control groups. The strength of the knee extensor and flexor muscles had time * group interactions: F = 29.604, P < 0.001 and F = 4.684, P = 0.015, respectively; the VFDWBV group had more improvement on lower-extremity muscle strength than the WBV and control groups. The 6-month follow-up showed that the rates of hospital visits for medical services due to falls were 0% in the WBV group (0/14), 0% in the VFDWBV group (0/17), and 28.57% in the control group (4/14).Results showed that WBV training at 20 Hz without visual feedback can significantly improve the balance performance and lower-extremity muscle strength of the elderly. PMID- 26844515 TI - Influence of H. pylori CagA Coupled with Alcohol Consumption on Cytokine Profiles in Men. AB - The aim of this study was to evaluate the effect of Helicobacter pylori (H pylori) cytotoxin-associated gene A (CagA) coupled with chronic alcohol ingestion on cytokine profiles.A total of 215 male subjects were divided into the following 4 groups: 130 alcohol H pylori CagA-negative consumers (CagA-) (group A), 50 alcohol H pylori CagA-positive consumers (CagA+) (group B), 24 nonalcohol H pylori CagA-negative consumers (group C), and 11 nonalcohol H pylori CagA positive consumers (group D). The serum CagA, C-reactive protein (CRP), interleukin (IL)-6, IL-10, E-selectin, adiponectin (ADP), and tumor necrosis factor-alpha (TNF-alpha) levels were measured through enzyme-linked immunosorbent assays (ELISAs).After adjusting for age and mean alcohol drinking history, a multivariable linear regression analysis revealed that the mean daily alcohol consumption, IL-6, TNF-alpha, and ADP levels were significantly increased with increases in the serum CagA concentrations (P = 0.008, P = 0.000, P = 0.000, and P = 0.006, respectively). The serum IL-6 and IL-10 levels of group A were significantly lower than those of group B (all P = 0.000). Furthermore, the serum IL-6 and IL-10 levels of groups A and C were significantly lower than those of group D (all P = 0.000), and the serum IL-6 and IL-10 levels of group C were significantly lower than those of group B (all P = 0.000). The serum ADP and E selectin levels of groups B and D were significantly higher than those of group A (P = 0.000). The serum ADP levels of group B were significantly higher than those of group C (P = 0.000), and the serum ADP and E-selectin levels of group C were significantly lower than those of group D (P = 0.000 and P = 0.005, respectively). Finally, the serum TNF-alpha levels of groups B, C, and D were significantly higher than those of group A (all P = 0.000), and the serum TNF alpha levels of group C were significantly higher than those of group D (P = 0.005).In conclusion, H pylori CagA may result in significantly higher levels of several inflammatory markers in both alcohol consumers and nonalcohol consumers. However, chronic alcohol ingestion coupled with H pylori CagA positivity does not result in significant changes in cytokine profiles. PMID- 26844516 TI - Preoperative Ratio of Neutrophils to Lymphocytes Predicts Postresection Survival in Selected Patients With Early or Intermediate Stage Hepatocellular Carcinoma. AB - This study aims to clarify the prognostic value of the preoperative neutrophil-to lymphocyte ratio (NLR) for patients with hepatocellular carcinoma (HCC) after potentially curative hepatic resection (HR). The prognostic value of the NLR for HCC patients has not been definitely reviewed by large studies, especially for those with different Barcelona Clinic Liver Cancer (BCLC) stages.A consecutive sample of 963 HCC patients who underwent potentially curative HR was classified as having low or high NLR using a cut-off value of 2.81. Overall survival (OS) and tumor recurrence were compared for patients with low or high NLR across the total population, as well as in subgroups of patients in BCLC stages 0/A, B, or C. Clinicopathological parameters, including NLR, were evaluated to identify risk factors of OS and tumor recurrence after potentially curative hepatic resection. Multivariate analyses were performed using the Cox proportional hazards model or subdistribution hazard regression model.Multivariate analyses showed that NLR (>2.81), tumor number (>3), incomplete capsule, serum albumin (<=35 g/L), alanine transaminase activity (>40 U/L), and macrovascular invasion were risk factors for low OS, whereas NLR (>2.81), tumor size (>5 cm), alpha fetal protein concentration (>400 ng/L), and macrovascular invasion were risk factors for low tumor recurrence. NLR > 2.81 was significantly associated with poor OS and tumor recurrence in the total patient population (both P < 0.001), as well as in the subgroups of patients in BCLC stages 0/A or B (all P < 0.05). Moreover, those with high NLR were associated with low OS (P = 0.027), and also with slightly higher tumor recurrence than those with low NLR for the subgroups in BCLC stage B (P = 0.058). Neither association, however, was observed among patients with BCLC stage C disease.NLR may be an independent predictor of low OS and tumor recurrence after potentially curative HR in HCC patients in BCLC stages 0/A or B. PMID- 26844517 TI - Association Between Reduced Risk of Intracerebral Hemorrhage and Pelvic Inflammatory Disease. AB - This study examines whether pelvic inflammatory disease (PID) facilitates the development of intracerebral hemorrhage (ICH).By using outpatient claims data from the National Health Insurance Research Database (NHIRD) of Taiwan, we included the data of 25,508 patients who were newly diagnosed with PID between 1999 and 2004, and also from the Taiwan NHIRD, we randomly selected 102,032 women without PID, who were frequency-matched by age and entry-year and with 4 times the number of the PID patients, as the control cohort. We measured ICH risks associated with PID and comorbidities, including hyperlipidemia, diabetes, hypertension, ischemic heart disease, and atrial fibrillation, by the end of 2011.In comparison with the controls, the ICH hazard was less in the PID group with an adjusted hazard ratio (aHR) of 0.67 (95% confidence interval [CI]:0.50 0.90), which was noted by calculation with the Cox proportional regression model. The ICH risk in the PID patients reduced progressively with the advance of age, with aHRs of 0.75 (95% CI:0.41-1.39) and 0.50 (95% CI:0.29-0.88), respectively, in the age <35-year and age >=50-year groups. ICH risk lowered gradually with the progress of PID severity, from mild PID with an aHR of 0.72 (95% CI:0.53-0.98) to severe PID with that of 0.30 (95% CI:0.10-0.92). PID patients without any comorbidites had lower ICH risk (aHR = 0.63, 95% CI:0.42-0.94) than the controls without any comorbidites did.Our findings revealed that PID is associated with reduced ICH development, especially for older patients. PMID- 26844518 TI - Incidence of Avascular Necrosis of the Femoral Head After Intramedullary Nailing of Femoral Shaft Fractures: A Multicenter Retrospective Analysis of 542 Cases. AB - The goal of this study was to determine the incidence of avascular necrosis of the femoral head (AVNFH) after intramedullary nailing of femoral shaft fractures and to identify risk factors for developing AVNFH.We retrospectively reviewed all patients with femoral shaft fractures treated with antegrade intramedullary nailing at 10 institutions. Among the 703 patients enrolled, 161 patients were excluded leaving 542 patients in the study. Average age was 42.1 years with average follow-up of 26.3 months. Patient characteristics and fracture patterns as well as entry point of femoral nails were identified and the incidence of AVNFH was investigated. Patients were divided into 2 groups according to open versus closed physis, open versus closed fractures, and age (<20 versus >=20 years).Overall incidence of AVNFH was 0.2% (1 of 542): the patient was 15-year old boy. Of 25 patients with open physis, the incidence of AVNFH was 4%, whereas none of 517 patients with closed physis developed AVNFH (P < 0.001). The incidence of AVNFH in patients aged < 20 versus >=20 years was 1.1% (1 of 93) and 0.0% (0 of 449), respectively (P = 0.172), which meant that the incidence of AVNFH was 0% in adult with femur shaft fracture. Of 61 patients with open fractures, the incidence of AVNFH was 0%. The number of cases with entry point at the trochanteric fossa or tip of the greater trochanter (GT) was 324 and 218, respectively, and the incidence of AVNFH was 0.3% and 0.0%, respectively (P = 0.412).In patients aged >=20 years with isolated femoral shaft fracture, there was no case of AVNFH following antegrade intramedullary nailing regardless of the entry point. Therefore, our findings suggest that the risk of AVNFH following antegrade femoral nailing is extremely low in adult patients. PMID- 26844519 TI - Performance of the Existing Classification Criteria for Gout in Thai Patients Presenting With Acute Arthritis. AB - Currently, there are 5 existing classification criteria for gout: the Rome, New York, American Rheumatism Association (ARA), Mexico, and Netherlands criteria. This study was carried out to determine the performance of these classification criteria in Thai patients presenting with acute arthritis.All consecutive patients presenting with acute arthritis and being consulted at the Rheumatology Unit, Chiang Mai University Hospital from January 2013 to May 2015 were invited to join the study. Gout was defined by the presence of monosodium urate crystals in the synovial fluid or tissue examined by experienced rheumatologists. The 5 existing gout classification criteria were performed and evaluated in all of the patients, who were divided in subgroups of early disease (<=2 years), established disease (>2 years), and those without tophus.There were 136 gout and 97 nongout patients. Sensitivity and specificity across all criteria ranged from 75.7% to 97.1% and 68.0% to 84.5%, respectively. Overall, the Mexico criteria had the highest sensitivity (97.1%), and the ARA survey criteria the highest specificity (84.5%), whereas the Mexico criteria performed well in early disease with sensitivity and specificity of 97.1% and 81.7%, respectively. All 5 criteria showed high sensitivity (from 76.4% to 99.1%) but low specificity (from 30.8% to 65.4%) in established disease. In patients without tophus, the sensitivity and specificity ranged from 64.1% to 95.7% and 68.8% to 85.4%, respectively. The ARA survey criteria across all groups showed consistently high specificity for gout.The 5 existing classification criteria for gout had limited sensitivity and specificity in Thai patients presenting with acute arthritis. The ARA survey criteria are the most suitable for diagnosing gout in Thai people when crystal identification is not available. PMID- 26844520 TI - Long-Term Single and Joint Effects of Excessive Daytime Napping on the HOMA-IR Index and Glycosylated Hemoglobin: A Prospective Cohort Study. AB - This prospective cohort study was conducted to assess the duration of daytime napping and its effect combined with night sleep deprivation on the risk of developing high HOMA-IR (homeostasis model assessment of insulin resistance) index and disadvantageous changes in glycosylated hemoglobin (HbA1c) levels.A total of 5845 diabetes-free subjects (2736 women and 3109 men), 30 to 65 years of age, were targeted for this cohort study since 2008. Multiple adjusted Cox regression models were performed to evaluate the single and joint effects of daytime napping on the risk of an elevated HbA1c level and high HOMA-IR index.After an average of 4.5 years of follow-up, >30 minutes of daytime napping was significantly associated with an increased risk of an elevated HbA1c level (>6.5%) in men and women (all P trend < 0.05). Hazard ratios (HRs) for an HbA1c level between 5.7% and 6.4% were also significant in the entire cohort and women, but nonsignificant in men. HRs (95% confidence interval, CIs) for the high HOMA IR index in the entire cohort, men, and women were 1.33 (1.10-1.62), 1.46 (1.08 1.98), and 1.47 (1.12-1.91), respectively. The combination of sleep deprivation with no naps or >30 minutes napping and the combination of no sleep deprivation with >30 minutes daytime napping were all associated with an HbA1c level >6.5% (HR = 2.08, 95% CI = 1.24-3.51; HR = 4.00, 95% CI = 2.03-7.90; and HR = 2.05, 95% CI = 1.29-3.27, respectively). No sleep deprivation combined with >30 minutes daytime napping correlated with a high risk of an HbA1c level between 5.7% and 6.4% and high HOMA-IR index (HR = 2.12, 95% CI = 1.48-3.02; and HR = 1.35, 95% CI = 1.10-1.65, respectively).Daytime napping >30 minutes was associated with a high risk of an elevated HbA1c level and high HOMA-IR index. No sleep deprivation combined with napping >30 minutes carries a risk of abnormal glucose metabolism. Sleep deprivation combined with brief daytime napping <30 minutes was not associated with a risk for an elevated HbA1c level and high HOMA-IR index. PMID- 26844521 TI - Exome Sequencing in a Family Identifies RECQL5 Mutation Resulting in Early Myocardial Infarction. AB - Coronary artery disease (CAD) including myocardial infarction (MI) is the leading cause of death worldwide and is commonly caused by the interaction between genetic factors and environmental risks. Despite intensive efforts using linkage and candidate gene approaches, the genetic etiology for the majority of families with a multigenerational early CAD /MI predisposition is unknown.In this study, we used whole-exome sequencing of 10 individuals from 1 early MI family, in which 4 siblings were diagnosed with MI before the age of 55, to identify potential predisposing genes.We identified a mutation in the RECQL5 gene, 1 of the 5 members of the RECQ family which are involved in the maintenance of genomic stability. This novel mutation, which is a TG insert at position 73,626,918 on the 13 chromosome and occurs before the last nucleotide of the introns 11 acceptor splice site affecting splicing of RECQL5. RT-PCR suggested the control subject had a full-length mRNA including exon 12, but the patients with RECQL5 mutation had a shorter mRNA form involving splicing of exons 11 to 13 directly, with skipping of exon 12. Quantitative RT-PCR analysis of RECQL5 exon 12 demonstrated that individuals whose genotype is mutant homozygote had only trace amounts of mRNA containing this exon and the family members who carry the heterozygous genotype had a level at 48% to 55% of the control's level.These findings provide insight into both the pathogenesis of MI and the role of RECQL5 gene in human disease. PMID- 26844522 TI - Neisseria meningitidis Serogroup C Causing Primary Arthritis in a Child: Case Report. AB - INTRODUCTION: Neisseria meningitidis (N. meningitidis) is associated with severe invasive infections such as meningitis and fulminant septicemia. Septic arthritis due to N. meningitidis is rare and bone infections have been reported exceptionally. We report the case of a 1-year old girl who presented with a painful, swollen right knee, accompanied by fever and agitation. Arthrocentesis of the right knee, while patient was under anesthesia, yielded grossly purulent fluid, so we made arthrotomy and drainage. The culture from synovial fluid revealed N. meningitidis, sensitive to Ceftriaxone. The patient received intravenous antibiotherapy with Ceftriaxone. The status of the patient improved after surgical drainage and intravenous antibiotic therapy. She recovered completely after 1 month. CONCLUSION: This observation illustrates an unusual presentation of invasive meningococcal infection and the early identification of the bacteria, combined with the correct treatment, prevent the complications and even death. PMID- 26844523 TI - A 7-Year Retrospective Multisource Analysis on the Incidence of Anesthesia Awareness With Recall in Cancer Patients: A Chance of Collaboration Between Anesthesiologists and Psycho-Oncologists for Awareness Detection. AB - Although randomized controlled studies reported an incidence of anesthesia awareness with recall ~1 to 2 per 1000 (0.1-0.2%), recent data from the NAP5 study showed an incidence of only 1:19,600. Although in a prospective study many tools for anesthesia awareness detection can be used, a retrospective analysis requires a careful collection of information.The aim of the study was to evaluate the incidence of anesthesia awareness with recall in a cohort of cancer patients through a multisource retrospective analysis, and the clinical description, including the psychological outcome, of the cases detected. We also tested whether our retrospective analysis would be improved by a routinely psycho oncological assessment. As secondary endpoints we evaluated the use of depth of anesthesia monitoring over a large cohort of patients, and the correlation between the brain monitoring and the incidence of awareness.We have carried out a 7-year retrospective analysis in a large cohort of cancer patients on the incidence of awareness with recall during general anesthesia. Of 35,595 patients assessed for eligibility, 21,099 were studied. We analyzed all data from the operative rooms' database, the anesthesia records, and from the database of the surgical divisions. In addition we examined reports from psychologists and spontaneous reports to the quality team of the hospital.Two certain cases of awareness were detected, with an incidence of 1:10,550 (0.0095%). They occurred during elective surgery, in female patients without other risk factors. One case came from the report of a psychologist. In both episodes, brain monitoring was not applied and no long-term psychological sequelae were reported.Despite the limitations, our investigation suggests that the incidence of anesthesia awareness is very low, also in a specific cohort of patients, such as the cancer patients, and even when the depth of anesthesia monitoring is rarely used. The limitations caused by both the retrospective analysis and the absence of specific tools for direct awareness detection, such as structured interviews, can be filled with an effective postoperative psychological assessment which is often of routine in a cancer center. This observation could suggest the usefulness of inserting specific questions within the psychological tools commonly used by psycho-oncologists. PMID- 26844525 TI - A novel zinc(II) and hydrogen sulphate selective fluorescent "turn-on" chemosensor based on isonicotiamide: INHIBIT type's logic gate and application in cancer cell imaging. AB - We have developed a novel isonicotiamide-based fluorescent "turn-on" chemosensor 1 for the selective detection of Zn(2+) and HSO4(-). The sensor 1 can detect Zn(2+) and HSO4(-) with a detection limit down to the nanomolar level by forming a complex in 1 : 1 stoichiometry in the presence of other anions and 2 : 1 in presence of cations in aqueous solution. Density functional theory calculations on 1 and the 1-Zn(2+)/HSO4(-) complexes are consistent with the experimental results. We have successfully utilized the above cation and anion for the fabrication of INHIBIT molecular logic gates. Furthermore the receptor 1 successfully detected the Zn(2+) and HSO4(-) ions in HeLa cells cultured in Zn(2+) and HSO4(-) enriched medium. PMID- 26844524 TI - The Highest Metabolic Activity on FDG PET Is Associated With Overall Survival in Limited-Stage Small-Cell Lung Cancer. AB - We evaluated the prognostic value of F-fluorodeoxyglucose positron emission tomography (FDG PET) parameters for limited-stage small-cell lung cancer (LS SCLC).We retrospectively enrolled 59 LS-SCLC patients who underwent pretreatment FDG PET/CT. Various PET parameters were measured in all malignant lesions, and we recorded the highest maximum standardized uptake value (SUVmax), and sum of metabolic tumor volume (MTVsum) and total lesion glycolysis (TLGsum). The relationship between the highest SUVmax and volumetric PET parameters was evaluated. The prognostic significances of PET parameters and clinical variables were assessed using Cox's proportional hazard regression analysis. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan Meier method.The SUVmax of the highest metabolic lesion had a significant positive correlation with MTVsum and TLGsum (P < 0.001). Upon multivariate analysis, the highest SUVmax was an independent predictor of OS (1 unit increase, hazard ratio [HR]: 1.133, P = 0.003) and MTVsum was a significant prognostic factor of PFS (10-cm increase, HR: 1.027, P = 0.034) after adjusting for age, sex, performance status, tumor stage, and treatment modality. The highest SUVmax was a prognostic factor for PFS with marginal significance (1 unit increase, HR: 1.078, P = 0.053). Patients with higher SUVmax (>=11) were also characterized by a significantly shorter median OS (P < 0.001) and PFS (P = 0.002) compared with patients with lower SUVmax.The highest SUVmax is an independent prognostic factor for survival in LS-SCLC patients. Therefore, the highest SUVmax might be a possible imaging biomarker for risk stratification in LS-SCLC. A further study in a large cohort is needed to validate the prognostic significance of the parameter. PMID- 26844526 TI - What can we learn about lipoprotein metabolism and coronary heart disease from studying rare variants? AB - PURPOSE OF REVIEW: Rare variant association studies (RVAS) target the class of genetic variation with frequencies less than 1%. Recently, investigators have used exome sequencing in RVAS to identify rare alleles responsible for Mendelian diseases but have experienced greater difficulty discovering such alleles for complex diseases. In this review, we describe what we have learned about lipoprotein metabolism and coronary heart disease through the conduct of RVAS. RECENT FINDINGS: Rare protein-altering genetic variation can provide important insights that are not as easily attainable from common variant association studies. First, RVAS can facilitate gene discovery by identifying novel rare protein-altering variants in specific genes that are associated with disease. Second, rare variant associations can provide supportive evidence for putative drug targets for novel therapies. Finally, rare variants can uncover new pathways and reveal new biologic mechanisms. SUMMARY: The field of human genetics has already made tremendous progress in understanding lipoprotein metabolism and the causes of coronary heart disease in the context of rare variants. As next generation sequencing becomes more cost-effective, RVAS with larger sample sizes will be conducted. This will lead to more novel rare variant discoveries and the translation of genomic data into biological knowledge and clinical insights for cardiovascular disease. PMID- 26844527 TI - Trimetazidine does not alter metabolic substrate oxidation in cardiac mitochondria of target patient population. AB - BACKGROUND AND PURPOSE: Trimetazidine, known as a metabolic modulator, is an anti anginal drug used for treatment of stable coronary artery disease (CAD). It is proposed to act via modulation of cardiac metabolism, shifting the mitochondrial substrate utilization towards carbohydrates, thus increasing the efficiency of ATP production. This mechanism was recently challenged; however, these studies used indirect approaches and animal models, which made their conclusions questionable. The goal of the current study was to assess the effect of trimetazidine on mitochondrial substrate oxidation directly in left ventricular myocardium from CAD patients. EXPERIMENTAL APPROACH: Mitochondrial fatty acid (palmitoylcarnitine) and carbohydrate (pyruvate) oxidation were measured in permeabilized left ventricular fibres obtained during coronary artery bypass grafting surgery from CAD patients, which either had trimetazidine included in their therapy (TMZ group) or not (Control). KEY RESULTS: There was no difference between the two groups in the oxidation of either palmitoylcarnitine or pyruvate, and in the ratio of carbohydrate to fatty acid oxidation. Activity and expression of pyruvate dehydrogenase, the key regulator of carbohydrate metabolism, were also not different. Lastly, acute in vitro exposure of myocardial tissue to different concentrations of trimetazidine did not affect myocardial oxidation of fatty acid. CONCLUSION AND IMPLICATIONS: Using myocardial tissue from CAD patients, we found that trimetazidine (applied chronically in vivo or acutely in vitro) had no effect on cardiac fatty acid and carbohydrate oxidation, suggesting that the clinical effects of trimetazidine are unlikely to be due to its metabolic effects, but rather to an as yet unidentified intracardiac mechanism. PMID- 26844529 TI - Can Social Cognitive Theories Help Us Understand Nurses' Use of Electronic Health Records? AB - Electronic health record implementations have accelerated in clinical settings around the world in an effort to improve patient safety and enhance efficiencies related to care delivery. As the largest group of healthcare professionals globally, nurses play an important role in the use of these records and ensuring their benefits are realized. Social cognitive theories such as the Theory of Reasoned Action, Theory of Planned Behaviour, and the Technology Acceptance Model have been developed to explain behavior. Given that variation in nurses' electronic health record utilization may influence the degree to which benefits are realized, the aim of this article is to explore how the use of these social cognitive theories may assist organizations implementing electronic health records to facilitate deeper-level adoption of this type of clinical technology. PMID- 26844530 TI - Erratum to "Changing channels in pain and epilepsy: Exploiting ion channel gene therapy for disorders of neuronal hyperexcitability" [FEBS Lett. 589 (2015) 1620 1634]. PMID- 26844528 TI - Oncogenic driver genes and the inflammatory microenvironment dictate liver tumor phenotype. AB - The majority of hepatocellular carcinoma develops in the background of chronic liver inflammation caused by viral hepatitis and alcoholic or nonalcoholic steatohepatitis. However, the impact of different types of chronic inflammatory microenvironments on the phenotypes of tumors generated by distinct oncogenes is largely unresolved. To address this issue, we generated murine liver tumors by constitutively active AKT-1 (AKT) and beta-catenin (CAT), followed by induction of chronic liver inflammation by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride. Also, the impact of DDC-induced chronic liver inflammation was compared between two liver tumor models using a combination of AKT-CAT or AKT-NRAS(G12V) . Treatment with DDC and carbon tetrachloride significantly facilitated the adenoma-to-carcinoma conversion and accelerated the growth of AKT-CAT tumors. Furthermore, DDC treatment altered the morphology of AKT-CAT tumors and caused loss of lipid droplets. Transcriptome analysis of AKT CAT tumors revealed that cellular growth and proliferation were mainly affected by chronic inflammation and caused up-regulation of Cxcl16, Galectin-3, and Nedd9, among others. Integration with transcriptome profiles from human hepatocellular carcinomas further demonstrated that AKT-CAT tumors generated in the context of chronic liver inflammation showed enrichment of poor prognosis gene sets or decrease of good prognosis gene sets. In contrast, DDC had a more subtle effect on AKT-NRAS(G12V) tumors and primarily enhanced already existent tumor characteristics as supported by transcriptome analysis. However, it also reduced lipid droplets in AKT-NRAS(G12V) tumors. CONCLUSION: Our study suggests that liver tumor phenotype is defined by a combination of driving oncogenes but also the nature of chronic liver inflammation. (Hepatology 2016;63:1888-1899). PMID- 26844532 TI - RNA recognition by Roquin in posttranscriptional gene regulation. AB - Posttranscriptional regulation of gene expression plays a central role in the initiation of innate and adaptive immune responses. This is exemplified by the protein Roquin, which has attracted great interest during the past decade owing to its ability to prevent autoimmunity. Roquin controls T-cell activation and T helper cell differentiation by limiting the induced expression of costimulatory receptors on the surface of T cells. It does so by recognizing cis regulatory RNA hairpin elements in the 3' UTR of target transcripts via its ROQ domain-a novel RNA-binding fold-and triggering their degradation through recruitment of factors that mediate deadenylation and decapping. Recent structural studies have revealed molecular details of the recognition of RNA hairpin structures by the ROQ domain. Surprisingly, it was found that Roquin mainly relies on shape-specific recognition of the RNA. This observation implies that a much broader range of RNA motifs could interact with the protein, but it also complicates systematic searches for novel mRNA targets of Roquin. Thus, large-scale approaches, such as crosslinking and immunoprecipitation or systematic evolution of ligands by exponential enrichment experiments coupled with next-generation sequencing, will be required to identify the complete spectrum of its target RNAs. Together with structural analyses of their binding modes, this will enable us to unravel the intricate complexity of 3' UTR regulation by Roquin and other trans-acting factors. Here, we review our current understanding of Roquin-RNA interactions and their role for Roquin function. WIREs RNA 2016, 7:455-469. doi: 10.1002/wrna.1333 For further resources related to this article, please visit the WIREs website. PMID- 26844533 TI - The H3F3 K36M mutant antibody is a sensitive and specific marker for the diagnosis of chondroblastoma. AB - AIMS: We recently reported that 95% of chondroblastomas harbour a p.K36M mutation in either H3F3A (chromosome 1) or H3F3B (chromosome 17), with the majority involving H3F3B. The aim of this study was to assess the expression of the K36M mutated protein by immunohistochemistry in a large group of tumours. METHODS AND RESULTS: One thousand eight hundred and ninety-four tumours, including 85 chondroblastomas and 10 clear-cell chondrosarcomas, were studied; of these, 82 chondroblastomas and one clear-cell chondrosarcoma known to harbour the H3F3 p.K36M mutation expressed the mutated protein. Three chondroblastomas and nine clear-cell chondrosarcomas wild type for H3F3A/H3F3B were negative for p.K36M immunoexpression. The remaining 1799 cases tested, 545 of which were known to be wild type for the H3F3A and H3F3B p.K36M mutations, included 1047 primary bone tumours, and 507 soft tissue and joint tumours. Two hundred and forty-five other tumour types not expected to harbour the mutation were negative for p.K36M immunoexpression. CONCLUSIONS: Our data demonstrate the specificity and sensitivity of this immunomarker, and will be a useful adjunct for reaching a diagnosis of chondroblastoma. PMID- 26844534 TI - Weight Loss, Xanthine Oxidase, and Serum Urate Levels: A Prospective Longitudinal Study of Obese Patients. AB - OBJECTIVE: The mechanisms by which weight loss decreases serum uric acid (SUA) levels are poorly known. We aimed to investigate the role played by xanthine oxidase (XOD), metabolic status, and low-grade inflammation in decreased SUA levels induced by weight loss in obese patients. METHODS: Data were from a series of consecutive patients with severe obesity involved in a bariatric surgery program. Measurements of body composition and biologic samples were obtained before surgery and 6 months after surgery. RESULTS: Among the 154 patients (mean +/- SD age 41.0 +/- 12.3 years, body mass index [BMI] 47.8 +/- 7.2 kg/m(2) , 81% female), the mean +/- SD weight loss at 6 months was 31.3 +/- 7.8 kg. Reduction in SUA levels was modest (-10%): 4.98 +/- 1.21 mg/dl at 6 months versus 5.52 +/- 1.33 mg/dl at baseline (P < 0.001). The decrease in SUA levels was greatest ( 18%) in hyperuricemic patients (n = 48). In these patients, circulating XOD activity decreased with weight loss (P < 0.0001). Multiple linear regression analysis revealed decreased SUA levels associated with decreased triglyceride levels (P = 0.0001) and BMI (P = 0.02) but not XOD activity, adipokine levels (leptin and adiponectin), insulin resistance, or levels of inflammatory variables (interleukin 6, orosomucoid, fibrinogen, and high-sensitivity C-reactive protein). CONCLUSION: In obese patients, weight loss was associated with a decrease in both SUA levels and XOD activity. Our findings suggest that reduced SUA levels are not mediated by decreased XOD activity or improved insulin resistance but could be partly due to a reduction in triglyceride levels. PMID- 26844535 TI - Development of a Two-Photon Fluorescent Probe for Imaging of Endogenous Formaldehyde in Living Tissues. AB - Investigation of the physiological and pathological functions of formaldehyde (FA) are largely restricted by a lack of useful FA imaging agents, in particular, those that allow detection of FA in the context of living tissues. Herein, we present the rational design, synthesis, and photophysical property studies of the first two-photon fluorescent FA probe, Na-FA. Importantly, the highly desirable attributes of the probe Na-FA (such as a very large turn-on signal (up to 900 fold), a low detection limit, and a very fast onset imparted by the unique design aspects of the probe), make it possible to monitor endogenous FA in living tissues for the first time. Furthermore, sodium bisulfite was identified as a simple and convenient inhibitor of FA within biological environments. PMID- 26844536 TI - Synthesis and in silico investigation of thiazoles bearing pyrazoles derivatives as anti-inflammatory agents. AB - Searching novel, safe and effective anti-inflammatory agents has remained an evolving research enquiry in the mainstream of inflammatory disorders. In the present investigation series of thiazoles bearing pyrazole as a possible pharmacophore were synthesized and assessed for their anti inflammatory activity using in vitro and in vivo methods. In order to decipher the possible anti inflammatory mechanism of action of the synthesized compounds, cyclooxygenase I and II (COX-I and COX-II) inhibition assays were also carried out. The results obtained clearly focus the significance of compounds 5d, 5h and 5i as selective COX-II inhibitors. Moreover, compound 5h was also identified as a lead molecule for inhibition of the carrageenin induced rat paw edema in animal model studies. Molecular docking results revealed significant interactions of the test compounds with the active site of COX-II, which perhaps can be explored for design and development of novel COX-II selective anti-inflammatory agents. PMID- 26844537 TI - Are leeches effective in local/regional skin flap salvage? PMID- 26844538 TI - Systematic Literature Review and Meta-Analysis of the Association of Sarcopenia With Mortality. AB - BACKGROUND: The World Health Organization (2002) indicates that the prevention of frailty is a key indicator of successful aging, and the assessment of the muscular system is the core for determining the frailty syndrome in older adults. Sarcopenia in older adults will affect more than 50 million people and will affect more than 200 million people after 40 years. Systematic literature reviews have yet to focus on the association between sarcopenia and mortality. AIMS: The aims of this study were to determine the correlation between sarcopenia and mortality by using various evaluation methods and to analyze any differences among the resulting correlations of the different assessment tools. METHODS: This study conducted a systematic review of relevant studies in four databases (Cochrane Library, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and Ovid). The inclusion criteria were prospective research, the results included mortality or death, and risk estimates included risk ratio or hazard ratio estimates and 95% confidence intervals. Exclusion criteria included studies that provided no sarcopenia data, the risk of mortality or death, or data indicating deaths from cancers and in hospitals. RESULTS: This study identified 10 studies that have investigated the association between sarcopenia and mortality with an average follow up of 4.17 years. In total, these studies have sampled 3,797 people and recorded 1,010 deaths. The result suggested that the risk of mortality in the sarcopenia group was higher than that in the nonsarcopenia group. LINKING EVIDENCE TO ACTION: Although the results of evidence based studies have suggested that sarcopenia is a geriatric syndrome associated with increased mortality, few studies have focused on decreasing sarcopenia mortality. Therefore, nurse practitioners must be aware of the correlation between sarcopenia and the mortality rate and become actively involved in developing intervention methods for reducing the mortality risk of sarcopenia. PMID- 26844539 TI - Beyond Conventional Quantum Dots. PMID- 26844540 TI - Extended epigenotype in a Rattus novergicus - Toxoplasma gondii association. AB - Several studies demonstrate that rats (Rattus novergicus) infected with protozoan parasite Toxoplasma gondii exhibit lesser fear to cat odors. This is thought to increase transmission of the parasite to its definitive hosts, i.e. cats. This is an example of extended phenotype where a gene of an organism allegedly creates a phenotype in another organism. We examined a possible proximate mechanism for this phenotype, describing an epigenetic change in arginine vasopressin gene in medial amygdala of male rats. Exogenously mimicking medial amygdala DNA hypomethylation resulted in reduction of fear to cat odors in uninfected animals, thus suggesting sufficiency. Systemic blockade of infection-induced DNA hypomethylation countermanded infection-induced behavioral change, thus suggesting necessity. This leads us to propose an epigenetic basis for this extended phenotype. PMID- 26844541 TI - Designing a new type of neutron detector for neutron and gamma-ray discrimination via GEANT4. AB - Design of a new type of neutron detector, consisting of a fast neutron converter, plastic scintillator, and Cherenkov detector, to discriminate 14-MeV fast neutrons and gamma rays in a pulsed n-gamma mixed field and monitor their neutron fluxes is reported in this study. Both neutrons and gamma rays can produce fluorescence in the scintillator when they are incident on the detector. However, only the secondary charged particles of the gamma rays can produce Cherenkov light in the Cherenkov detector. The neutron and gamma-ray fluxes can be calculated by measuring the fluorescence and Cherenkov light. The GEANT4 Monte Carlo simulation toolkit is used to simulate the whole process occurring in the detector, whose optimum parameters are known. Analysis of the simulation results leads to a calculation method of neutron flux. This method is verified by calculating the neutron fluxes using pulsed n-gamma mixed fields with different n/gamma ratios, and the results show that the relative errors of all calculations are <5%. PMID- 26844542 TI - Analysis of the radiation shielding of the bunker of a 230MeV proton cyclotron therapy facility; comparison of analytical and Monte Carlo techniques. AB - The neutron ambient dose equivalent outside the radiation shield of a proton therapy cyclotron vault is estimated using the unshielded dose equivalent rates and the attenuation lengths obtained from the literature and by simulations carried out with the FLUKA Monte Carlo radiation transport code. The source terms derived from the literature and that obtained from the FLUKA calculations differ by a factor of 2-3, while the attenuation lengths obtained from the literature differ by 20-40%. The instantaneous dose equivalent rates outside the shield differ by a few orders of magnitude, not only in comparison with the Monte Carlo simulation results, but also with the results obtained by line of sight attenuation calculations with the different parameters obtained from the literature. The attenuation of neutrons caused by the presence of bulk iron, such as magnet yokes is expected to reduce the dose equivalent by as much as a couple of orders of magnitude outside the shield walls. PMID- 26844543 TI - Effect of Pattern and Duration of Breastfeeding on the Consumption of Fruits and Vegetables among Preschool Children. AB - BACKGROUND: The duration and pattern of breastfeeding can influence the consumption of fruits and vegetables in later childhood. OBJECTIVE: To investigate the association between pattern and duration of breastfeeding and consumption of fruits and vegetables in children aged between 4 and 7 years. METHODS: We conducted a secondary analysis using data from a former randomized clinical trial with 323 adolescent mothers, their children, and maternal grandmothers, when they cohabited. Information on infant feeding was collected monthly during the first 6 months of life, every two months until the child was 1 year old over and when children were between 4 and 7 years old. The associations between duration of breastfeeding and exclusive breastfeeding and consumption of fruits and vegetables were tested by a logistic regression model. RESULTS: Approximately 60% and 45% of children consumed fruits and vegetables, respectively, five or more times a week. Consumption of vegetables among 4-7-year old children was higher in children who were breastfed for 12 months or longer (OR 2.7; 95%CI 1.49-4.93); however, exclusive breastfeeding duration did not have a significant association with consumption of vegetables (OR 1.5; 95%CI 0.70 3.04). There was no association between weekly consumption of fruits and duration of breastfeeding (OR 1.3; 95%CI 0.71-2.30) or exclusive breastfeeding (OR 0.7; 95%CI 0.34-1.44). CONCLUSIONS: Longer duration of breastfeeding was positively associated with consumption of vegetables in children aged 4-7 years; however, there was no association with consumption of fruits. Exclusive breastfeeding duration did not have influence on consumption of fruits or vegetables. PMID- 26844545 TI - Semaphorins and Plexins in Kidney Disease. AB - Semaphorins are soluble or membrane-bound cues, which control multiple aspects of cell-cell communication, differentiation, morphology and function. Most of their effects are mediated by a family of transmembrane receptors called plexins. Semaphorins and plexins have emerged as central regulators of diverse physiological and pathophysiological processes in various organs. This review summarizes the role of semaphorins and plexins in renal pathophysiology and their potential use as biomarkers of kidney disease. PMID- 26844544 TI - Convolution Comparison Pattern: An Efficient Local Image Descriptor for Fingerprint Liveness Detection. AB - We present a new type of local image descriptor which yields binary patterns from small image patches. For the application to fingerprint liveness detection, we achieve rotation invariant image patches by taking the fingerprint segmentation and orientation field into account. We compute the discrete cosine transform (DCT) for these rotation invariant patches and attain binary patterns by comparing pairs of two DCT coefficients. These patterns are summarized into one or more histograms per image. Each histogram comprises the relative frequencies of pattern occurrences. Multiple histograms are concatenated and the resulting feature vector is used for image classification. We name this novel type of descriptor convolution comparison pattern (CCP). Experimental results show the usefulness of the proposed CCP descriptor for fingerprint liveness detection. CCP outperforms other local image descriptors such as LBP, LPQ and WLD on the LivDet 2013 benchmark. The CCP descriptor is a general type of local image descriptor which we expect to prove useful in areas beyond fingerprint liveness detection such as biological and medical image processing, texture recognition, face recognition and iris recognition, liveness detection for face and iris images, and machine vision for surface inspection and material classification. PMID- 26844547 TI - Threshold Games and Cooperation on Multiplayer Graphs. AB - OBJECTIVE: The study investigates the effect on cooperation in multiplayer games, when the population from which all individuals are drawn is structured-i.e. when a given individual is only competing with a small subset of the entire population. METHOD: To optimize the focus on multiplayer effects, a class of games were chosen for which the payoff depends nonlinearly on the number of cooperators-this ensures that the game cannot be represented as a sum of pair wise interactions, and increases the likelihood of observing behaviour different from that seen in two-player games. The chosen class of games are named "threshold games", and are defined by a threshold, M > 0, which describes the minimal number of cooperators in a given match required for all the participants to receive a benefit. The model was studied primarily through numerical simulations of large populations of individuals, each with interaction neighbourhoods described by various classes of networks. RESULTS: When comparing the level of cooperation in a structured population to the mean-field model, we find that most types of structure lead to a decrease in cooperation. This is both interesting and novel, simply due to the generality and breadth of relevance of the model-it is likely that any model with similar payoff structure exhibits related behaviour. More importantly, we find that the details of the behaviour depends to a large extent on the size of the immediate neighbourhoods of the individuals, as dictated by the network structure. In effect, the players behave as if they are part of a much smaller, fully mixed, population, which we suggest an expression for. PMID- 26844546 TI - A Missense LRRK2 Variant Is a Risk Factor for Excessive Inflammatory Responses in Leprosy. AB - BACKGROUND: Depending on the epidemiological setting, a variable proportion of leprosy patients will suffer from excessive pro-inflammatory responses, termed type-1 reactions (T1R). The LRRK2 gene encodes a multi-functional protein that has been shown to modulate pro-inflammatory responses. Variants near the LRRK2 gene have been associated with leprosy in some but not in other studies. We hypothesized that LRRK2 was a T1R susceptibility gene and that inconsistent association results might reflect different proportions of patients with T1R in the different sample settings. Hence, we evaluated the association of LRRK2 variants with T1R susceptibility. METHODOLOGY: An association scan of the LRRK2 locus was performed using 156 single-nucleotide polymorphisms (SNPs). Evidence of association was evaluated in two family-based samples: A set of T1R-affected and a second set of T1R-free families. Only SNPs significant for T1R-affected families with significant evidence of heterogeneity relative to T1R-free families were considered T1R-specific. An expression quantitative trait locus (eQTL) analysis was applied to evaluate the impact of T1R-specific SNPs on LRRK2 gene transcriptional levels. PRINCIPAL FINDINGS: A total of 18 T1R-specific variants organized in four bins were detected. The core SNP capturing the T1R association was the LRRK2 missense variant M2397T (rs3761863) that affects LRRK2 protein turnover. Additionally, a bin of nine SNPs associated with T1R were eQTLs for LRRK2 in unstimulated whole blood cells but not after exposure to Mycobacterium leprae antigen. SIGNIFICANCE: The results support a preferential association of LRRK2 variants with T1R. LRRK2 involvement in T1R is likely due to a pathological pro-inflammatory loop modulated by LRRK2 availability. Interestingly, the M2397T variant was reported in association with Crohn's disease with the same risk allele as in T1R suggesting common inflammatory mechanism in these two distinct diseases. PMID- 26844548 TI - Expression and Prognostic Significance of Human Epidermal Growth Factor Receptors 1 and 3 in Gastric and Esophageal Adenocarcinoma. AB - BACKGROUND: Gastric and esophageal adenocarcinomas are major global cancer burdens. These cancer forms are characterized by a poor prognosis and a modest response to chemo- radio- and targeted treatment. Hence there is an obvious need for further enhanced diagnostic and treatment strategies. The aim of this study was to examine the expression and prognostic impact of human epidermal growth factor receptor 1 (HER1/EGFR) and 3 (HER3), as well as the occurrence of EGFR and KRAS mutations in gastric and esophageal adenocarcinoma. METHODS: Immunohistochemical expression of EGFR and HER3 was analysed in all primary tumours and a subset of lymph node metastases in a consecutive cohort of 174 patients with adenocarcinoma of the stomach, cardia and esophagus. The anti-HER3 antibody used was validated by siRNA-mediated knockdown, immunohistochemistry and quantitative real-time PCR. EGFR and KRAS mutation status was analysed by pyrosequencing tecchnology. RESULTS AND DISCUSSION: High EGFR expression was an independent risk factor for shorter overall survival (OS), whereas high HER3 expression was associated with a borderline significant trend towards a longer OS. KRAS mutations were present in only 4% of the tumours and had no prognostic impact. All tumours were EGFR wild-type. These findings contribute to the ongoing efforts to decide on the potential clinical value of different HERs and druggable mutations in gastric and esophageal adenocarcinomas, and attention is drawn to the need for more standardised investigational methods. PMID- 26844549 TI - Evolutionary Genomics Suggests That CheV Is an Additional Adaptor for Accommodating Specific Chemoreceptors within the Chemotaxis Signaling Complex. AB - Escherichia coli and Salmonella enterica are models for many experiments in molecular biology including chemotaxis, and most of the results obtained with one organism have been generalized to another. While most components of the chemotaxis pathway are strongly conserved between the two species, Salmonella genomes contain some chemoreceptors and an additional protein, CheV, that are not found in E. coli. The role of CheV was examined in distantly related species Bacillus subtilis and Helicobacter pylori, but its role in bacterial chemotaxis is still not well understood. We tested a hypothesis that in enterobacteria CheV functions as an additional adaptor linking the CheA kinase to certain types of chemoreceptors that cannot be effectively accommodated by the universal adaptor CheW. Phylogenetic profiling, genomic context and comparative protein sequence analyses suggested that CheV interacts with specific domains of CheA and chemoreceptors from an orthologous group exemplified by the Salmonella McpC protein. Structural consideration of the conservation patterns suggests that CheV and CheW share the same binding spot on the chemoreceptor structure, but have some affinity bias towards chemoreceptors from different orthologous groups. Finally, published experimental results and data newly obtained via comparative genomics support the idea that CheV functions as a "phosphate sink" possibly to off-set the over-stimulation of the kinase by certain types of chemoreceptors. Overall, our results strongly suggest that CheV is an additional adaptor for accommodating specific chemoreceptors within the chemotaxis signaling complex. PMID- 26844550 TI - The Influence of a Metal Stent on the Distribution of Thermal Energy during Irreversible Electroporation. AB - PURPOSE: Irreversible electroporation (IRE) uses short duration, high-voltage electrical pulses to induce cell death via nanoscale defects resulting from altered transmembrane potential. The technique is gaining interest for ablations in unresectable pancreatic and hepatobiliary cancer. Metal stents are often used for palliative biliary drainage in these patients, but are currently seen as an absolute contraindication for IRE due to the perceived risk of direct heating of the metal and its surroundings. This study investigates the thermal and tissue viability changes due to a metal stent during IRE. METHODS: IRE was performed in a homogeneous tissue model (polyacrylamide gel), without and with a metal stent placed perpendicular and parallel to the electrodes, delivering 90 and 270 pulses (15-35 A, 90 MUsec, 1.5 cm active tip exposure, 1.5 cm interelectrode distance, 1000-1500 V/cm, 90 pulses/min), and in-vivo in a porcine liver (4 ablations). Temperature changes were measured with an infrared thermal camera and with fiber optic probes. Tissue viability after in-vivo IRE was investigated macroscopically using 5-triphenyltetrazolium chloride (TTC) vitality staining. RESULTS: In the gel, direct stent-heating was not observed. Contrarily, the presence of a stent between the electrodes caused a higher increase in median temperature near the electrodes (23.2 vs 13.3 degrees C [90 pulses]; p = 0.021, and 33.1 vs 24.8 degrees C [270 pulses]; p = 0.242). In-vivo, no temperature difference was observed for ablations with and without a stent. Tissue examination showed white coagulation 1mm around the electrodes only. A rim of vital tissue remained around the stent, whereas ablation without stent resulted in complete tissue avitality. CONCLUSION: IRE in the vicinity of a metal stent does not cause notable direct heating of the metal, but results in higher temperatures around the electrodes and remnant viable tissue. Future studies should determine for which clinical indications IRE in the presence of metal stents is safe and effective. PMID- 26844552 TI - Cytogenetic Biomonitoring in Buccal Mucosa Cells from Young Smokers. AB - OBJECTIVE: Nowadays, much attention has been focused on the search for new non invasive methodologies able to predict malignant transformation of oral mucosa cells. The aim of the present study was to comparatively evaluate DNA damage (micronucleus) and cellular death (pyknosis, karyolysis and karyorrhexis) in exfoliated oral mucosa cells from smokers and non-smokers in buccal mucosa cells. STUDY DESIGN: A total of 24 young, healthy smokers and 14 non-smokers were included in this setting. Individuals had epithelial cells from the cheek mechanically exfoliated, placed in fixative and dropped in clean slides which were checked for the above nuclear phenotypes. RESULTS: Smokers presented more (p < 0.05) micronucleated oral mucosa cells than non-smokers. Tobacco smoke was not able to increase other nuclear alterations closely related to cytotoxicity such as karyorrhexis, pyknosis and karyolysis. CONCLUSION: In summary, these data indicate that the cigarette is able to induce micronuclei in oral mucosa cells, so the micronucleus test is a suitable method for predicting oral cancer risk. PMID- 26844551 TI - A TCRbeta Repertoire Signature Can Predict Experimental Cerebral Malaria. AB - Cerebral Malaria (CM) is associated with a pathogenic T cell response. Mice infected by P. berghei ANKA clone 1.49 (PbA) developing CM (CM+) present an altered PBL TCR repertoire, partly due to recurrently expanded T cell clones, as compared to non-infected and CM- infected mice. To analyse the relationship between repertoire alteration and CM, we performed a kinetic analysis of the TRBV repertoire during the course of the infection until CM-related death in PbA infected mice. The repertoires of PBL, splenocytes and brain lymphocytes were compared between infected and non-infected mice using a high-throughput CDR3 spectratyping method. We observed a modification of the whole TCR repertoire in the spleen and blood of infected mice, from the fifth and the sixth day post infection, respectively, while only three TRBV were significantly perturbed in the brain of infected mice. Using multivariate analysis and statistical modelling, we identified a unique TCRbeta signature discriminating CM+ from CTR mice, enriched during the course of the infection in the spleen and the blood and predicting CM onset. These results highlight a dynamic modification and compartmentalization of the TCR diversity during the course of PbA infection, and provide a novel method to identify disease-associated TCRbeta signature as diagnostic and prognostic biomarkers. PMID- 26844554 TI - Normative Nasalance Scores for Brazilian Portuguese Using New Speech Stimuli. AB - OBJECTIVE: Normative data were established for newly developed speech materials for nasalance assessment in Brazilian Portuguese. MATERIALS AND METHODS: Nasalance scores of preexisting passages (oral ZOO-BR, low-pressure oral ZOO-BR2 and NASAL-BR), new nasalance passages (oral Dudu no zoologico, oral Dudu no bosque, oral-nasal O caozinho Toto and nasal O nene) and Brasilcleft articulation screening sentences were collected from 245 speakers of Brazilian Portuguese, including 121 males and 124 females, divided into 4 groups: children (5-9 years), adolescents (10-19 years), young adults (20-24 years) and adults (25-35 years). RESULTS: Across all nasalance passages, adult females scored on average 2 percentage points higher than males. Children scored 2-4 percentage points lower than older groups for the preexisting nasalance passages ZOO-BR and ZOO-BR2. Nasalance scores for the new nasalance passages were not significantly different from the preexisting passages. Scores for high-pressure sentences did not differ significantly from the oral nasalance passage Dudu no bosque. CONCLUSION: The nasalance scores for the new nasalance passages were equivalent to the preexisting materials. The new shortened and simplified nasalance passages will be useful for assessing young children. Normative scores for the Brasilcleft high pressure sentences were equivalent to the new oral passage Dudu no bosque. PMID- 26844553 TI - Flagellin Encoded in Gene-Based Vector Vaccines Is a Route-Dependent Immune Adjuvant. AB - Flagellin has been tested as a protein-based vaccine adjuvant, with the majority of studies focused on antibody responses. Here, we evaluated the adjuvant activity of flagellin for both cellular and humoral immune responses in BALB/c mice in the setting of gene-based immunization, and have made several novel observations. DNA vaccines and adenovirus (Ad) vectors were engineered to encode mycobacterial protein Ag85B, with or without flagellin of Salmonella typhimurium (FliC). DNA-encoded flagellin given IM enhanced splenic CD4+ and CD8+ T cell responses to co-expressed vaccine antigen, including memory responses. Boosting either IM or intranasally with Ad vectors expressing Ag85B without flagellin led to durable enhancement of Ag85B-specific antibody and CD4+ and CD8+ T cell responses in both spleen and pulmonary tissues, correlating with significantly improved protection against challenge with pathogenic aerosolized M. tuberculosis. However, inclusion of flagellin in both DNA prime and Ad booster vaccines induced localized pulmonary inflammation and transient weight loss, with route-dependent effects on vaccine-induced T cell immunity. The latter included marked reductions in levels of mucosal CD4+ and CD8+ T cell responses following IM DNA/IN Ad mucosal prime-boosting, although antibody responses were not diminished. These findings indicate that flagellin has differential and route dependent adjuvant activity when included as a component of systemic or mucosally delivered gene-based prime-boost immunization. Clear adjuvant activity for both T and B cell responses was observed when flagellin was included in the DNA priming vaccine, but side effects occurred when given in an Ad boosting vector, particularly via the pulmonary route. PMID- 26844555 TI - Biotechnological Fluorescent Ligands of the Bradykinin B1 Receptor: Protein Ligands for a Peptide Receptor. AB - The bradykinin (BK) B1 receptor (B1R) is a peculiar G protein coupled receptor that is strongly regulated to the point of being inducible in immunopathology. Limited clinical evidence suggests that its expression in peripheral blood mononuclear cells is a biomarker of active inflammatory states. In an effort to develop a novel imaging/diagnostic tool, we report the rational design and testing of a fusion protein that is a ligand of the human B1R but not likely to label peptidases. This ligand is composed of a fluorescent protein (FP) (enhanced green FP [EGFP] or mCherry) prolonged at its N-terminus by a spacer peptide and a classical peptide agonist or antagonist (des-Arg9-BK, [Leu8]des-Arg9-BK, respectively). The design of the spacer-ligand joint peptide was validated by a competition assay for [3H]Lys-des-Arg9-BK binding to the human B1R applied to 4 synthetic peptides of 18 or 19 residues. The labeling of B1R-expressing cells with EGFP or mCherry fused with 7 of such peptides was performed in parallel (microscopy). Both assays indicated that the best design was FP-(Asn-Gly)n-Lys des-Arg9-BK; n = 15 was superior to n = 5, suggesting benefits from minimizing steric hindrance between the FP and the receptor. Cell labeling concerned mostly plasma membranes and was inhibited by a B1R antagonist. EGFP-(Asn-Gly)15-Lys-des Arg9-BK competed for the binding of [3H]Lys-des-Arg9-BK to human recombinant B1R, being only 10-fold less potent than the unlabeled form of Lys-des-Arg9-BK to do so. The fusion protein did not label HEK 293a cells expressing recombinant human BK B2 receptors or angiotensin converting enzyme. This study identifies a modular C-terminal sequence that can be adapted to protein cargoes, conferring high affinity for the BK B1R, with possible applications in diagnostic cytofluorometry, histology and drug delivery (e.g., in oncology). PMID- 26844557 TI - Drug Target Validation Methods in Malaria - Protein Interference Assay (PIA) as a Tool for Highly Specific Drug Target Validation. AB - BACKGROUND: The validation of drug targets in malaria and other human diseases remains a highly difficult and laborious process. In the vast majority of cases, highly specific small molecule tools to inhibit a proteins function in vivo are simply not available. Additionally, the use of genetic tools in the analysis of malarial pathways is challenging. These issues result in difficulties in specifically modulating a hypothetical drug target's function in vivo. OBJECTIVE: The current "toolbox" of various methods and techniques to identify a protein's function in vivo remains very limited and there is a pressing need for expansion. New approaches are urgently required to support target validation in the drug discovery process. METHOD: Oligomerisation is the natural assembly of multiple copies of a single protein into one object and this self-assembly is present in more than half of all protein structures. Thus, oligomerisation plays a central role in the generation of functional biomolecules. A key feature of oligomerisation is that the oligomeric interfaces between the individual parts of the final assembly are highly specific. However, these interfaces have not yet been systematically explored or exploited to dissect biochemical pathways in vivo. RESULTS AND CONCLUSION: This mini review will describe the current state of the antimalarial toolset as well as the potentially druggable malarial pathways. A specific focus is drawn to the initial efforts to exploit oligomerisation surfaces in drug target validation. As alternative to the conventional methods, Protein Interference Assay (PIA) can be used for specific distortion of the target protein function and pathway assessment in vivo. PMID- 26844558 TI - Immunotherapy and Hormone-therapy in Metastatic Breast Cancer: A Review and an Update. AB - Historically, antiestrogen is the first targeted therapy used in breast cancer treatment. In fact, its rationale lies in the molecular pathways elucidated by basic research. In estrogen receptor (ER)-alpha positive metastatic breast cancer patients, hormone-therapy remains the first option of treatment. While tamoxifen concomitant with suppression of ovarian function with luteinizing hormone releasing hormone (LHRH) agonists is the standard first line treatment in premenopausal, third generation aromatase inhibitors (AIs) are the first line standard hormone therapy in postmenopausal. However, the development of acquired resistance during antiestrogen therapy continues to be a central clinical problem. This review provides an update on the antiestrogen action and report on immunological treatment of the advanced disease by some cytokines. Interleukin-2, interleukin-12 and interferons used alone or in combination demonstrated an anti tumor action directly and/or through synergism with antiestrogens. A rationale for the addition of interferon-beta and interleukin-2 to antiestrogens is described. Furthermore, we summarize and interpret the clinical and laboratory data of a recent long-term hormone- immunotherapy study in metastatic endocrine dependent breast cancer patients. Prospective randomized trials are necessary to confirm some recent promising results based on an immunological approach in addition to antiestrogens to overcome or delay acquired hormone resistance. PMID- 26844559 TI - Elastin-Like Recombinamers As Smart Drug Delivery Systems. AB - BACKGROUND: Drug delivery systems that are able to control the release of bioactive molecules and designed to carry drugs to target sites are of particular interest for tissue therapy. Moreover, systems comprising materials that can respond to environmental stimuli and promote self-assembly and higher order supramolecular organization are especially useful in the biomedical field. Objetive: This review focuses on biomaterials suitable for this purpose and that include elastin-like recombinamers (ELRs), a class of proteinaceous polymers bioinspired by natural elastin, designed using recombinant technologies. The self assembly and thermoresponsive behaviour of these systems, along with their biodegradability, biocompatibility and well-defined composition as a result of their tailormade design, make them particularly attractive for controlled drug delivery. RESULTS: ELR-based delivery systems that allow targeted delivery are reviewed, especially ELR-drug recombinant fusion constructs, ELR-drug systems chemically bioconjugated in their monomeric and soluble forms, and drug encapsulation by nanoparticle-forming ELRs. Subsequently, the review focuses on those drug carriers in which smart release is triggered by pH or temperature with a particular focus on cancer treatments. Systems for controlled drug release based on depots and hydrogels that act as both a support and reservoir in which drugs can be stored will be described, and their applications in drug delivery discussed. Finally, smart drug-delivery systems not based on ELRs, including those comprising proteins, synthetic polymers and non-polymeric systems, will also be briefly discussed. CONCLUSION: Several different constructions based on ELRs are potential candidates for controlled drug delivery to be applied in advanced biomedical treatments. PMID- 26844556 TI - Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment. AB - Cytosolic NADPH-dependent reductase AKR1B10 is a member of the aldo-keto reductase (AKR) superfamily. This enzyme is normally expressed in the gastrointestinal tract. However, it is overexpressed in many solid tumors, such as hepatocarcinoma, lung cancer and breast cancer. AKR1B10 may play a role in the formation and development of carcinomas through multiple mechanisms including detoxification of cytotoxic carbonyls, modulation of retinoic acid level, and regulation of cellular fatty acid synthesis and lipid metabolism. Studies have suggested that AKR1B10 may be a useful biomarker for cancer diagnosis and a potential target for cancer treatment. Over the last decade, a number of AKR1B10 inhibitors including aldose reductase inhibitors (ARIs), endogenous substances, natural-based derivatives and synthetic compounds have been developed, which could be novel anticancer drugs. This review provides an overview on related articles and patents about AKR1B10 inhibitors, with a focus on their inhibition selectivity and mechanism of function. PMID- 26844560 TI - Therapeutic Targeting of CD6 in Autoimmune Diseases: A Review of Cuban Clinical Studies with the Antibodies IOR-T1 and Itolizumab. AB - The CD6 molecule is a pan T cell marker involved in T cell regulation. Although CD6 expression has been correlated with human autoimmune diseases, only a few therapeutic approaches are exploring this molecule as target in the clinic. The biological functions and mechanisms of actions of CD6 have not been definitively established. It is probable that this molecule plays a dual role as a modulator of intracellular signaling. Itolizumab is a humanized monoclonal antibody specific for human CD6, developed at the Center of Molecular Immunology in Havana, Cuba. Its parent murine antibody, the IOR-T1 mAb, had been obtained in the 80's at the Institute of Oncology and Radiology, also in Havana. This article provides an overview of the clinical data obtained in Cuban patients with autoimmune diseases who have been treated with IOR-T1 mAb or itolizumab. Furthermore, we discuss the possible mechanism of action of itolizumab basing the analysis on recent site mutagenesis and structural data, which, contrary to previous interpretations, points to a steric blocking of the CD6-CD166 interaction in the cellular context. Overall, the conducted clinical studies have demonstrated that itolizumab has favorable clinical effects and a safety profile when used as monotherapy in patients with rheumatoid arthritis and psoriasis. So far, in vitro and in vivo evidences indicate that itolizumab has immunomodulatory and anti-inflammatory effects. Hence, itolizumab represents a new therapeutic option for autoimmune diseases such as rheumatoid arthritis and psoriasis. PMID- 26844561 TI - Soft Computing Techniques for the Protein Folding Problem on High Performance Computing Architectures. AB - The protein-folding problem has been extensively studied during the last fifty years. The understanding of the dynamics of global shape of a protein and the influence on its biological function can help us to discover new and more effective drugs to deal with diseases of pharmacological relevance. Different computational approaches have been developed by different researchers in order to foresee the threedimensional arrangement of atoms of proteins from their sequences. However, the computational complexity of this problem makes mandatory the search for new models, novel algorithmic strategies and hardware platforms that provide solutions in a reasonable time frame. We present in this revision work the past and last tendencies regarding protein folding simulations from both perspectives; hardware and software. Of particular interest to us are both the use of inexact solutions to this computationally hard problem as well as which hardware platforms have been used for running this kind of Soft Computing techniques. PMID- 26844563 TI - Withdrawn: Review on efficacy and complications of granulocyte transfusions in neutropenic patients. AB - Withdrawn by the publisher. PMID- 26844562 TI - Can microRNAs be Biomarkers or Targets for Therapy of Ischemic Coronary Artery Disease in Metabolic Syndrome? AB - BACKGROUND: Due to their exceptional stability in the circulation, microRNAs (miRs) are being identified as promising biomarkers. On the other hand, their propensity to regulate networks of functionally closely related genes and relative ease of delivery makes them attractive targets for therapy. However, neither application is without challenges, especially as it applies to ischemic coronary artery disease (CAD). OBJECTIVE: This review will: 1) describe miRs which have been most consistently found to be associated with the most common manifestations of CAD, including atherosclerosis, angina pectoris, myocardial infarction and myocardial reperfusion through arteriogenesis, 2) emphasize those miRs which are also altered in metabolic syndrome and its component pathologies, 3) discuss challenges which currently prevent clinical application related to inconsistencies between findings in cell culture, animal models and among human studies, as well as technical challenges, and 4) offer some suggestions towards resolutions of these discrepancies. CONCLUSION: While miRs can be used as reliable biomarkers for myocardial infarction, their use as biomarkers for other forms of ischemic CAD, as well as therapy for CAD await further investigation. PMID- 26844564 TI - Role of Interferons in Chronic Hepatitis C Infection. AB - It is known that the production of and/or response to interferon (IFN) are deregulated during chronic hepatitis C virus (HCV) infection. In particular, several studies have shown that patients with chronic HCV infection who have a high natural level of IFN-stimulated genes (ISGs) do not achieve viral clearance and have a poor response to treatment with pegylated IFNalpha and ribavirin. The viral and/or host factors that are responsible for the higher endogenous ISGs expression in some HCV infected patients compared to others remain to be determined. However, type III IFNs, and in particular the new discovered IFN lambda (L) 4 Gene, appear to play a dominant role in driving ISGs response and in contributing to the establishment of HCV persistence. This review focuses on recent studies on how the ISGs response and the IFNlambda genetic factors (interleukin-28B and IFNL4) affect the clinical outcome of HCV infection highlighting their impact in the current antiviral therapies with direct acting antiviral agents. PMID- 26844565 TI - Hepatitis C Virus-Associated B-Cell Non-Hodgkin's Lymphoma: Clinical and Therapeutic Challenges. AB - Hepatitis C virus (HCV) is a major cause of liver-related morbidity and is strongly associated with B-cell lymphoproliferative disorders. Data from epidemiological, biological and clinical investigations support the hypothesis of a pathogenetic role of HCV in at least a subgroup of patients with B-cell non Hodgkin's lymphoma (B-NHL). Morphologically, HCV-associated B-NHL represents a variety of histological subtypes. The comprehension of the mechanisms of HCV persistence and of its role in the lymphomagenesis will be useful to set new strategies with the aim to prevent and treat HCV-associated B-NHLs. This hypothesis of a virus-induced mechanism of lymphomagenesis arises from the growing evidence that successful antiviral treatment is often linked to regression of some types of HCV-related indolent B-NHLs. PMID- 26844566 TI - Nuclear Factor Kappa B: A Potential Target to Persecute Head and Neck Cancer. AB - Despite the consistent and significant advancements made in the treatment of head and neck cancer (HNSCC), it remains one of the most devastating cancers globally killing approximately 350,000 people every year. Both clinical and basic research revealed that the transcription factor NF-kappaB, is constitutively expressed in HNSCC and this persistent expression of NF-kappaB is the root cause of this disease resulting in cancer cell proliferation, survival, invasion, metastases and poor survival of patients. Activation of NF-kappaB is pragmatic in most of the premalignant dysplastic lesions indicating it as an early episode in malignant transformation of this disease. Therefore, therapies designed to inhibit or block the activity of NF-kappaB, would result in downregulation of key cellular processes involved in tumor growth and its dissemination to metastatic sites. In addition, substantial evidences have revealed that NF-kappaB plays an indispensable role in the development of both chemo and radiation resistance in HNSCC which is identified to be a primary cause for the failure of therapies. This shows the potential of targeting NF- kappaB in developing therapies against this disease. This review summarises the role of NF-kappaB in the development of HNSCC and the potential of using NF-kappaB as a target to develop novel highly effective therapies for this disease. PMID- 26844567 TI - Neuroinflammation is Associated with Brain Extracellular TAU-Protein Release After Spontaneous Subarachnoid Hemorrhage. AB - INTRODUCTION: Animal data suggest an association between neuroinflammation and secondary brain injury including axonal injury after aneurysmal subarachnoid hemorrhage (aSAH). We sought to study the association between brain extracellular interleukin (IL)-6 and TAU-protein levels as a surrogate marker for neuroinflammation and axonal injury in patients with poor grade aSAH. METHODS: Prospectively collected data from 26 consecutive poor-grade aSAH patients with multimodal neuromonitoring including cerebral microdialysis (CMD) were retrospectively analyzed. IL-6 and TAU-protein levels were analyzed using ELISA from a single CMD-sample every 24 hours and correlated with brain metabolic and hemodynamic parameters. Patients were dichotomized to highgrade (N=10) or low grade (N=16) neuroinflammation according to their median CMD-IL-6 levels. Data were analyzed using generalized estimating equations to account for multiple within-subject measurements. RESULTS: Perilesional probe location (P=0.02) and aSAH related intracerebral hemorrhage (aICH) volume (P=0.003) at admission were associated with high-grade neuroinflammation. Brain extracellular TAU-protein levels (P=0.001), metabolic distress and delayed cerebral infarction (DCI; P=0.001) were linked to high-grade neuroinflammation. Relative or absolute phosphor-TAU levels were not correlated with CMD-IL-6 levels. High-grade neuroinflammation was a predictor for worse outcome three months after ictus, independently from probe location, initial Hunt&Hess grade and age (P=0.01). CONCLUSION: Neuroinflammation after aSAH is associated with intraparenchymal bleeding, deranged cerebral metabolism and TAU-protein release. The impact of potential anti-inflammatory treatment strategies on secondary brain injury after aSAH has to be investigated in future studies. PMID- 26844568 TI - Biophysical Screening for Identifying Pharmacological Chaperones and Inhibitors Against Conformational and Infectious Diseases. AB - Experimental and computational screenings are currently widespread tools for identifying either potential ligands for a given target or potential targets for a given chemical compound. In particular, ligand-induced stabilization against thermal denaturation (or thermal shift assay) is an easy and convenient experimental procedure for finding compounds able to control the activity of a protein target (e.g., allosteric or competitive inhibitors interfering with its activity, allosteric activators enhancing its activity, or pharmacological chaperones avoiding aggregation, unfolding or degradation). Despite its simplicity the thermal shift assay does not lack some important drawbacks. Here we describe this methodology, its application to structured and unstructured protein targets, and we discuss successful cases of identification of bioactive compounds for conformational disorders associated to loss of function (phenylketonuria) and infectious diseases (gastric ulcer and hepatitis C). PMID- 26844569 TI - The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations. AB - The cell surface glycoprotein CD6 is expressed on leukocytes and mediates T cell trafficking across endothelial cell barriers. There is evidence suggesting that CD6 is implicated in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and rheumatoid arthritis (RA). CD166, the physiological ligand of CD6, is expressed on endothelial cells in the central nervous system and in the collagen tissue of joints as well as on the cell surface of synovial fibroblasts. Animal models and in vitro experiments have shown that CD166 facilitates leukocyte trafficking into the central nervous system and mediates interactions of synovial cells with T lymphocytes, thereby representing a possible common mechanism of pathogenesis in MS and RA. In recent years, genome-wide association studies (GWAS) have established a genetic link between CD6 and MS. The single nucleotide polymorphism (SNP) rs17824933 in the CD6 gene has been identified and validated as a genetic risk factor for the development of MS. The SNP is associated with altered CD4+ T cell functions and with the expression of alternative CD6 splice variants in T cells. Several other independent CD6 gene polymorphisms have been associated with disease susceptibility or with clinical features such as worse attack recovery in MS. In addition to the genetic associations found in MS, an allelic variant of the CD6 gene correlates with clinical response to tumor necrosis factor-alpha (TNF-alpha) inhibitors in patients with RA. Preliminary data indicate that anti-CD6 blockade may be a promising tool for the treatment of RA and psoriasis. Taken together, genetic associations and clinical observations provide new evidence for a role of CD6 in autoimmunity. PMID- 26844570 TI - Portals and Web-Based Resources for Virtual Screening. AB - Virtual screening for active compounds has become an essential step within the drug development pipeline. The computer based prediction of compound binding modes is one of the most time and cost efficient methods for screening ligand libraries and enrich results of potential drugs. Here we present an overview about currently available online resources regarding compound databases, docking applications, and science gateways for drug discovery and virtual screening, in order to help structural biologists in choosing the best tools for their analysis. The appearance of the user interface, authentication and security aspects, data management, and computational performance will be discussed. We anticipate a broad overview about currently available solutions, guiding computational chemists and users from related fields towards scientifically reliable results. PMID- 26844571 TI - AMPK as a New Attractive Therapeutic Target for Disease Prevention: The Role of Dietary Compounds AMPK and Disease Prevention. AB - AMPK is a serine/threonine protein kinase that has the function of maintaining the balance between ATP production and consumption in most eukaryotic cells. It plays a relevant role in regulating cellular metabolism, preserving cellular energy homeostasis, and is involved in many other cellular processes as well as metabolic ones, including cell cycle regulation and endothelial and vascular relaxation. Recently, the effects of naturally occurring compounds able to prevent and treat diseases through AMPK activation have attracted the attention of many researchers. Among such compounds, flavonoids found in natural sources, like quercetin, genistein, epigallocatechins, resveratrol, have been proposed as AMPK activators. This review summarizes and updates the most recent findings concerning the mechanisms through which different dietary compounds, from plant foods, affect the AMPK pathway in healthy and pathological in vitro and in vivo models, paying particular attention to molecular mechanisms involved in diabetes, obesity, metabolic syndrome, cardiovascular disease and cancer. PMID- 26844572 TI - Emerging Immunotargets in Bladder Cancer. AB - Bladder cancer treatment, namely systemic therapy, was dominated in the last three decades due to the absence of newer therapeutic options other than chemotherapy regimens. Chemotherapy, by itself, both in first and second-line seems to have achieved the modest plateau of its possibilities at the cost of non negligible toxicity. Targeted therapies, which changed the therapy of many different tumors, seem rather ineffective in bladder cancer. More recently, a new generation of Immunotherapy based regimens represent the most promising avenue for the future systemic treatment of bladder cancer. Checkpoint inhibition, namely PD1/PD-L1 pathway inhibition, showed impressive results in many other tumor types and are expected to become a major player in the treatment of bladder cancer. Other immunotherapy strategies such as fusion proteins represent distant, although promising, options. A brief overview of the current status of bladder cancer immunotherapy is presented. PMID- 26844573 TI - Review of the Third Domain Receptor Binding Fragment of Alphafetoprotein (AFP): Plausible Binding of AFP to Lysophospholipid Receptor Targets. AB - Alpha-fetoprotein (AFP) is a 69 kD fetal- and tumor-associated single-chain glycoprotein belonging to the albuminoid gene family. AFP functions as a carrier/transport molecule as well as a growth regulator and has been utilized as a clinical biomarker for both fetal defects and cancer growth. Lysophospholipids (LPLs) are plasma membrane-derived bioactive lipid signaling mediators composed of a small molecular weight single acyl carbon chain (palmitic, oleic acid) attached to a polar headgroup; they range in molecular mass from 250-750 daltons. The LPLs consist of either sphingosine-1-phosphate or lysophosphatidic acid, and mostly their choline, ethanolamine, serine or inositol derivatives. They are present only in vertebrates. These bioactive paracrine lipid mediators are ubiquitously distributed in tissues and are released from many different cell types (platelets, macrophages, monocytes, etc.) involved in developmental, physiological, and pathological processes. The LPLs bind to four different classes of G-protein coupled receptors described herein which transduce a multiple of cell effects encompassing activities such as morphogenesis, neural development, angiogenesis, and carcinogenesis. The identification of potential binding sites of LPL receptors on the AFP third domain receptor binding fragment was derived by computer modeling analysis. It is conceivable, but not proven, that AFP might bind not only to the LPL receptors, but also to LPLs themselves since AFP binds medium and long chain fatty acids. It is proposed that some of the activities ascribed to AFP in the past might be due in part to the presence of bound LPLs and/or their receptors. PMID- 26844574 TI - Similar task features shape judgment and categorization processes. AB - The distinction between similarity-based and rule-based strategies has instigated a large body of research in categorization and judgment. Within both domains, the task characteristics guiding strategy shifts are increasingly well documented. Across domains, past research has observed shifts from rule-based strategies in judgment to similarity-based strategies in categorization, but limited these comparisons to 1 prototypical environment, a linear task structure, and a restricted set of strategies. To systematically compare the 2 domains, we considered several instantiations of rule-based and similarity-based strategies and examined strategy choice across different types of judgment and categorization tasks. Between participants, we varied task characteristics from a 1-dimensional linear to a multidimensional linear and to 2 multidimensional nonlinear tasks. Irrespective of domain, strategies considered, or model comparison technique used, we find that more participants relied on similarity based strategies when the functional relationship between the cues and the criterion was nonlinear. Shifts from rule-based strategies in judgment to similarity-based strategies in categorization, however, were rare and most pronounced in 1-dimensional environments. These results support the hypothesis that the cognitive strategies people select to solve a judgment or categorization task depend less on the domain but more on the complexity of the task. (PsycINFO Database Record PMID- 26844575 TI - Memory for recently accessed visual attributes. AB - Recent reports have suggested that the attended features of an item may be rapidly forgotten once they are no longer relevant for an ongoing task (attribute amnesia). This finding relies on a surprise memory procedure that places high demands on declarative memory. We used intertrial priming to examine whether the representation of an item's identity is lost completely once it becomes task irrelevant. If so, then the identity of a target on one trial should not influence performance on the next trial. In 3 experiments, we replicated the finding that a target's identity is poorly recognized in a surprise memory test. However, we also observed location and identity repetition priming across consecutive trials. These data suggest that, although explicit recognition on a surprise memory test may be impaired, some information about a particular target's identity can be retained after it is no longer needed for a task. (PsycINFO Database Record PMID- 26844576 TI - Forgetting the literal: The role of inhibition in metaphor comprehension. AB - In order for a person to comprehend metaphoric expressions, do metaphor irrelevant aspects of literal information need to be inhibited? Previous research using sentence-verification paradigms has found that literal associates take longer to process after reading metaphorical sentences; however, it is problematic to infer inhibition from this research. Moreover, previous work has not distinguished between familiar and novel metaphor processing. To test more directly for when inhibition may be required during metaphor processing, we performed 3 experiments using a metaphor-induced lexical forgetting paradigm. Participants initially learned word pairs where the cues were potential metaphoric vehicles and the targets were literal associates (e.g., SHARK-swim). Then, participants read half the vehicles as part of metaphorical sentences, which they interpreted (The lawyer for the defense is a shark). Subsequent forgetting of the literal associates was greater when vehicles had appeared in metaphorical sentences (Experiment 1) and was observed for both familiar and novel metaphors when participants were instructed to interpret the metaphors (Experiment 2) but was observed for only novel metaphors when participants were instructed to simply read the metaphors (Experiment 3). These results suggest that forgetting occurs as a result of inhibitory mechanisms that are engaged to alter activation of irrelevant literal information during metaphor processing, and that these mechanisms are most relevant for the processing demands associated with novel metaphors. PMID- 26844578 TI - Picture-perfect is not perfect for metamemory: Testing the perceptual fluency hypothesis with degraded images. AB - The perceptual fluency hypothesis claims that items that are easy to perceive at encoding induce an illusion that they will be easier to remember, despite the finding that perception does not generally affect recall. The current set of studies tested the predictions of the perceptual fluency hypothesis with a picture generation manipulation. Participants identified mixed lists of intact images and images whose certain parts were deleted (generate condition) and made predictions about their subsequent memory performance, followed by a recall test. The intact condition always produced higher memory predictions and shorter identification latencies than the generate condition, consistent with the perceptual fluency hypothesis (Experiments 1 to 3). The actual memory performance for generate images was higher than intact images when aggregate judgments of learning (JOLs) were used (Experiment 1) and equivalent to intact images when item-by-item JOLs were used (Experiment 2 to 3). In Experiment 3, introducing a manipulation that facilitates naming latency for generate images did not increase JOL ratings, providing evidence that not all manipulations that facilitate the ease of perception produce higher JOLs. In Experiment 4, the role of a priori beliefs for the picture generation manipulation was assessed through an online questionnaire. Reading a scenario about the manipulation produced no JOL differences for intact and generate images. The results of the 4 experiments reported here are generally consistent with the perceptual fluency hypothesis of metamemory, and are discussed in terms of experience-based and theory-based processes in metamemory judgments and Koriat's (1997) cue utilization framework. (PsycINFO Database Record PMID- 26844577 TI - Sound-symbolism boosts novel word learning. AB - The existence of sound-symbolism (or a non-arbitrary link between form and meaning) is well-attested. However, sound-symbolism has mostly been investigated with nonwords in forced choice tasks, neither of which are representative of natural language. This study uses ideophones, which are naturally occurring sound symbolic words that depict sensory information, to investigate how sensitive Dutch speakers are to sound-symbolism in Japanese in a learning task. Participants were taught 2 sets of Japanese ideophones; 1 set with the ideophones' real meanings in Dutch, the other set with their opposite meanings. In Experiment 1, participants learned the ideophones and their real meanings much better than the ideophones with their opposite meanings. Moreover, despite the learning rounds, participants were still able to guess the real meanings of the ideophones in a 2-alternative forced-choice test after they were informed of the manipulation. This shows that natural language sound-symbolism is robust beyond 2 alternative forced-choice paradigms and affects broader language processes such as word learning. In Experiment 2, participants learned regular Japanese adjectives with the same manipulation, and there was no difference between real and opposite conditions. This shows that natural language sound-symbolism is especially strong in ideophones, and that people learn words better when form and meaning match. The highlights of this study are as follows: (a) Dutch speakers learn real meanings of Japanese ideophones better than opposite meanings, (b) Dutch speakers accurately guess meanings of Japanese ideophones, (c) this sensitivity happens despite learning some opposite pairings, (d) no such learning effect exists for regular Japanese adjectives, and (e) this shows the importance of sound-symbolism in scaffolding language learning. (PsycINFO Database Record PMID- 26844579 TI - Using mental transformation strategies for spatial scaling: Evidence from a discrimination task. AB - Spatial scaling, or an understanding of how distances in different-sized spaces relate to each other, is fundamental for many spatial tasks and relevant for success in numerous professions. Previous research has suggested that adults use mental transformation strategies to mentally scale spatial input, as indicated by linear increases in response times and accuracies with larger scaling magnitudes. However, prior research has not accounted for possible difficulties in encoding spatial information within smaller spaces. Thus, the present study used a discrimination task in which we systematically pitted absolute size of the spaces against scaling magnitude. Adults (N = 48) were presented with 2 pictures, side by-side on a computer display, each of which contained a target. Adults were asked to decide whether the targets were in the same position or not, by pressing the respective computer key. In the constant-large condition, the constant space was kept large, whereas the size of the other space was variable and smaller. In the constant-small condition, the constant space was small, whereas the size of the other space was variable and larger. Irrespective of condition, adults' discrimination performance (d-primes) and response times were linear functions of scaling magnitude, supporting the notion that analog imagery strategies are used in spatial scaling. (PsycINFO Database Record PMID- 26844580 TI - Parafoveal processing in silent and oral reading: Reading mode influences the relative weighting of phonological and semantic information in Chinese. AB - We examined how reading mode (i.e., silent vs. oral reading) influences parafoveal semantic and phonological processing during the reading of Chinese sentences, using the gaze-contingent boundary paradigm. In silent reading, we found in 2 experiments that reading times on target words were shortened with semantic previews in early and late processing, whereas phonological preview effects mainly occurred in gaze duration or second-pass reading. In contrast, results showed that phonological preview information is obtained early on in oral reading. Strikingly, in oral reading, we observed a semantic preview cost on the target word in Experiment 1 and a decrease in the effect size of preview benefit from first- to second-pass measures in Experiment 2, which we hypothesize to result from increased preview duration. Taken together, our results indicate that parafoveal semantic information can be obtained irrespective of reading mode, whereas readers more efficiently process parafoveal phonological information in oral reading. We discuss implications for notions of information processing priority and saccade generation during silent and oral reading. (PsycINFO Database Record PMID- 26844581 TI - Spatiotemporal proximity effects in visual short-term memory examined by target nontarget analysis. AB - Visual short-term memory (VSTM) is a limited-capacity system that holds a small number of objects online simultaneously, implying that competition for limited storage resources occurs (Phillips, 1974). How the spatial and temporal proximity of stimuli affects this competition is unclear. In this 2-experiment study, we examined the effect of the spatial and temporal separation of real-world memory targets and erroneously selected nontarget items examined during location recognition and object-recall tasks. In Experiment 1 (the location-recognition task), our test display comprised either the picture or name of 1 previously examined memory stimulus (rendered above as the stimulus-display area), together with numbered square boxes at each of the memory-stimulus locations used in that trial. Participants were asked to report the number inside the square box corresponding to the location at which the cued object was originally presented. In Experiment 2 (the object-recall task), the test display comprised a single empty square box presented at 1 memory-stimulus location. Participants were asked to report the name of the object presented at that location. In both experiments, nontarget objects that were spatially and temporally proximal to the memory target were confused more often than nontarget objects that were spatially and temporally distant (i.e., a spatiotemporal proximity effect); this effect generalized across memory tasks, and the object feature (picture or name) that cued the test-display memory target. Our findings are discussed in terms of spatial and temporal confusion "fields" in VSTM, wherein objects occupy diffuse loci in a spatiotemporal coordinate system, wherein neighboring locations are more susceptible to confusion. (PsycINFO Database Record PMID- 26844582 TI - Superior cognitive mapping through single landmark-related learning than through boundary-related learning. AB - Cognitive mapping is assumed to be through hippocampus-dependent place learning rather than striatum-dependent response learning. However, we proposed that either type of spatial learning, as long as it involves encoding metric relations between locations and reference points, could lead to a cognitive map. Furthermore, the fewer reference points to specify individual locations, the more accurate a cognitive map of these locations will be. We demonstrated that participants have more accurate representations of vectors between 2 locations and of configurations among 3 locations when locations are individually encoded in terms of a single landmark than when locations are encoded in terms of a boundary. Previous findings have shown that learning locations relative to a boundary involve stronger place learning and higher hippocampal activation whereas learning relative to a single landmark involves stronger response learning and higher striatal activation. Recognizing this, we have provided evidence challenging the cognitive map theory but favoring our proposal. (PsycINFO Database Record PMID- 26844583 TI - Beginning at the beginning: Recall order and the number of words to be recalled. AB - When participants are asked to recall a short list of words in any order that they like, they tend to initiate recall with the first list item and proceed in forward order, even when this is not a task requirement. The current research examined whether this tendency might be influenced by varying the number of items that are to be recalled. In 3 experiments, participants were presented with short lists of between 4 and 6 words and instructed to recall 1, 2, 3, or all of the items from the lists. Data were collected using immediate free recall (IFR, Experiment 1), immediate serial recall (ISR, Experiment 2), and a variant of ISR that we call ISR-free (Experiment 3), in which participants had to recall words in their correct serial positions but were free to output the words in any order. For all 3 tasks, the tendency to begin recall with the first list item occurred only when participants were required to recall as many items from the list as they could. When participants were asked to recall only 1 or 2 items, they tended to initiate recall with end-of-list items. It is argued that these findings show for the first time a manipulation that eliminates the initial tendency to recall in forward order, provide some support for recency-based accounts of IFR and help explain differences between single-response and multiple-response immediate memory tasks. (PsycINFO Database Record PMID- 26844585 TI - Mechanism for Forming B,C,N,O Rings from NH3BH3 and CO2 via Reaction Discovery Computations. AB - This study employs computational reaction finding tools to probe the unique biphilic reactivity between ammonia-borane (AB) and CO2. The results show that sequential reactions involving multiple equivalents of AB and CO2 can lead to the formation of stable nonplanar B,C,N,O-heterocycles (Cy-BCN). Cy-BCN is shown to emerge through boron-oxygen bond formation, hydroboration, dative bond formation, and single- or double-hydrogen transfers. The most kinetically facile reactions (computed at the coupled cluster singles and doubles with perturbative triples (CCSD(T)) level of theory) result from polarized nitrogen-boron double bonds whereas thermodynamic stability results from formation of covalent boron-oxygen bonds. An important structure, HCOOBHNH2 (DHFAB), contains both of these features and is the key intermediate involved in generation of Cy-BCN. Crucially, it is shown that favorable boron-oxygen bond formation results in production of Cy-BCN species that are more stable than polyaminoboranes. These types of reaction intermediates could serve as building blocks in the formation of B,N-codoped graphene oxide (BCN). PMID- 26844586 TI - Characterization of Matured Vermicompost Derived from Valorization of Palm Oil Mill Byproduct. AB - The valorization process involves transforming low-value materials such as wastes into high-value-added products. The current study aims to determine the potential of using a valorization process such as vermicomposting technology to convert palm oil mill byproduct, namely, decanter cake (DC), into organic fertilizer or vermicompost. The maturity of the vermicompost was characterized through various chemical and instrumental characterization to ensure the end product was safe and beneficial for agricultural application. The vermicomposting of DC showed significantly higher nutrient recovery and decreases in C:N ratio in comparison with the controls, particularly in the treatment with 2 parts DC and 1 part rice straw (w/w) (2DC:1RS). 2DC:1RS vermicompost had a final C:N ratio of 9.03 +/- 0.12 and reasonably high levels of calcium (1.13 +/- 0.05 g/kg), potassium (25.47 +/- 0.32 g/kg), magnesium (4.87 +/- 0.19 g/kg), sodium (7.40 +/- 0.03 g/kg), and phosphorus (3.62 +/- 0.27 g/kg). In addition, instrumental characterization also revealed a higher degree of maturity in the vermicompost. Ratios of 2921:1633 and DTG2:DTG3 also showed significant linear correlations with the C:N ratio, implying that those ratios could be used to characterize the progression of vermicompost maturity during the valorization process of DC. PMID- 26844584 TI - Diurnal salivary cortisol patterns prior to pregnancy predict infant birth weight. AB - OBJECTIVE: Elevated maternal psychosocial stress during pregnancy and accompanying changes in stress hormones may contribute to risk of adverse birth outcomes such as low birth weight and preterm birth. Relatedly, research on fetal programming demonstrates intriguing associations between maternal stress processes during pregnancy and outcomes in offspring that extend into adulthood. The purpose of this study was to test whether hypothalamic-pituitary-adrenal (HPA) patterns in mothers during the period between 2 pregnancies (i.e., the interpregnancy interval) and during the subsequent pregnancy predict infant birth weight, a key birth outcome. METHOD: This study sampled salivary cortisol before and during pregnancy in a diverse community sample of 142 women enrolled in the Community Child Health Network study. RESULTS: Using multilevel modeling, we found that flatter diurnal cortisol slopes in mothers during the interval between one birth and a subsequent pregnancy predicted lower infant birth weight of the subsequent child. This interpregnancy cortisol pattern in mothers also correlated with significantly shorter interpregnancy intervals, such that women with flatter cortisol slopes had more closely spaced pregnancies. After adding demographic covariates of household income, cohabitation with partner, and maternal race to the model, these results were unchanged. For participants who provided both interpregnancy and pregnancy cortisol data (n = 73), we found that interpregnancy cortisol slopes predicted infant birth weight independent of pregnancy cortisol slopes. CONCLUSIONS: These novel findings on interpregnancy HPA axis function and subsequent pregnancy outcomes strongly support life course health approaches and underscore the importance of maternal stress physiology between pregnancies. (PsycINFO Database Record PMID- 26844588 TI - Self-Healing Spongy Coating for Drug "Cocktail" Delivery. AB - Optimized ratio in the codelivery of therapeutics is of crucial importance to promote the synergism rather than the antagonistic effects. In this study, a self healing spongy coating was described to facilitate the surface-mediated delivery of drug "cocktails" proportionally. The formation of spongy structures within the coating was achieved by acidic treatment and freeze-drying. Various drug combinations can be readily integrated through wicking method and subsequent micropore self-healing. The ratio of drug loading can be precisely regulated by the composition of loading solution and the embedded drugs were released in proportion according to the initial ratio of drug combination. PMID- 26844587 TI - Helquat Dyes: Helicene-like Push-Pull Systems with Large Second-Order Nonlinear Optical Responses. AB - Helquat dyes combine a cationic hemicyanine with a helicene-like motif to form a new blueprint for chiral systems with large and tunable nonlinear optical (NLO) properties. We report a series of such species with characterization, including determination of static first hyperpolarizabilities beta0 via hyper-Rayleigh scattering and Stark spectroscopy. The measured beta0 values are similar to or substantially larger than that of the commercial chromophore E-4'-(dimethylamino) N-methyl-4-stilbazolium. Density functional theory (DFT) and time-dependent DFT calculations on two of the new cations are used to probe their molecular electronic structures and optical properties. Related molecules are expected to show bulk second-order NLO effects in even nonpolar media, overcoming a key challenge in developing useful materials. PMID- 26844589 TI - Poly(ethylene oxide) Mushrooms Adsorbed at Silica-Ionic Liquid Interfaces Reduce Friction. AB - The adsorbed layer conformation and lubricity of 35, 100, and 300 kDa PEO adsorbed to ionic liquid (IL)-silica interfaces from 0.01 wt % solutions have been investigated using colloid probe atomic force microscopy. The ILs used were propylammonium nitrate (PAN) and 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]), which are protic and aprotic ILs, respectively. Normal force curves reveal steric interactions consistent with adsorbed polymer layers which are best fit using the mushroom model. Friction measurements show that the adsorbed polymer layer markedly reduces friction compared to surfaces sliding in the pure ILs and that lubricity increases with polymer length. When polymer is adsorbed to the sliding surfaces, friction is controlled by the creation and disruption of intermolecular interactions between entangled chains and the dragging of polymer chains through the interpenetration region. These experiments show that added polymer can reduce friction while maintaining the useful properties of ILs as lubricants. PMID- 26844590 TI - Amyloid Plaque in the Human Brain Can Decompose from Abeta(1-40/1-42) by Spontaneous Nonenzymatic Processes. AB - The degradation of long-lived proteins in the body is an important aspect of aging, and much of the breakdown is due to the intrinsic instability of particular amino acids. In this study, peptides were examined to discover if spontaneous nonenzymatic reactions could be responsible for the composition of Alzheimer's (AD) plaque in the human brain. The great majority of AD plaque consists of N-terminally truncated versions of Abeta(1-40/1-42), with the most abundant peptide commencing with Glu (residue 3 in Abeta1-40/1-42) that is present as pyroGlu. Several Asp residues are racemized in Abeta plaque, with residue 1 being predominantly l-isoAsp and peptide bond cleavage next to Ser 8 is also evident. In peptides, loss of the two N-terminal amino acids as a diketopiperazine was demonstrated at pH 7. For the Abeta N-terminal hexapeptide, AspAlaGluPheArgHis, this resulted in the removal of AspAla diketopiperazine and the generation of Glu as the new N-terminal residue. The Glu cyclized readily to pyroGlu. This pathway was altered significantly by zinc, which promoted pyroGlu formation but decreased AspAla diketopiperazine release. Zinc also facilitated cleavage on the N-terminal side of Ser 8. Racemization of the original N-terminal Asp to l-isoAsp was also detected and loss of one amino acid from the N-terminus. These data are therefore entirely consistent with plaque in the human brain forming from deposition of Abeta(1-40/1-42) and, over time, decomposing spontaneously. Since amyloid plaque is present in the human brain for years prior to the onset of AD, gradual spontaneous changes to the polypeptides within it will alter its properties and those of the oligomers that can diffuse from it. Such incremental changes in composition may therefore contribute to the origin of AD-associated cytotoxicity. PMID- 26844591 TI - Synthesis of Azacyclic Nucleoside Analogues via Asymmetric [3 + 2] Cycloaddition of 9-(2-Tosylvinyl)-9H-purines. AB - With 9-(2-tosylvinyl)-9H-purines as the dipolarophiles, a series of chiral azacyclic nucleosides with four continuous stereocenters were obtained in 86-99% yields, >20:1 dr, and 94 -> 99% ee via the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition. Both (E)- and (Z)-9-(2-tosylvinyl)-9H-purines were suitable dipolarophiles, enriching the structure diversity of azacyclic nucleosides. Furthermore, when alpha-methyl imino ester was explored, the corresponding azacyclic nucleoside with a chiral quaternary stereocenter could also be afforded with excellent results. PMID- 26844592 TI - Mitochondria-Targeting Ceria Nanoparticles as Antioxidants for Alzheimer's Disease. AB - Mitochondrial oxidative stress is a key pathologic factor in neurodegenerative diseases, including Alzheimer's disease. Abnormal generation of reactive oxygen species (ROS), resulting from mitochondrial dysfunction, can lead to neuronal cell death. Ceria (CeO2) nanoparticles are known to function as strong and recyclable ROS scavengers by shuttling between Ce(3+) and Ce(4+) oxidation states. Consequently, targeting ceria nanoparticles selectively to mitochondria might be a promising therapeutic approach for neurodegenerative diseases. Here, we report the design and synthesis of triphenylphosphonium-conjugated ceria nanoparticles that localize to mitochondria and suppress neuronal death in a 5XFAD transgenic Alzheimer's disease mouse model. The triphenylphosphonium conjugated ceria nanoparticles mitigate reactive gliosis and morphological mitochondria damage observed in these mice. Altogether, our data indicate that the triphenylphosphonium-conjugated ceria nanoparticles are a potential therapeutic candidate for mitochondrial oxidative stress in Alzheimer's disease. PMID- 26844593 TI - Introducing Dimensionality to the Archetypical Mn12 Single-Molecule Magnet: a Family of [Mn12]n Chains. AB - The [Mn12O12(O2CR)16(L4)] family (R = various; L = terminal ligand) of clusters holds a special place in molecular magnetism; they are the most well-studied single-molecule magnets (SMMs). Targeted linkage of these SMMs has now been achieved for the first time. The resulting chain structures have been confirmed crystallographically, and the magnetic properties, up to 1.14 GPa, and high-field electron paramagnetic resonance spectra have been collected and analyzed. PMID- 26844594 TI - Bottom-up Electrosynthesis of Highly Active Tungsten Sulfide (WS3-x) Films for Hydrogen Evolution. AB - Transition metal dichalcogenides have been extensively studied as promising earth abundant electrocatalysts for hydrogen evolution reaction (HER). However, despite the intention to achieve sustainable energy generation, conventional syntheses typically use environmentally damaging reagents and energy-demanding preparation conditions. Hence, we present electrochemical synthesis as a green and versatile alternative to traditional methods. In this fundamental study, we demonstrated the bottom-up synthesis of a mixed WS2/WS3 film-like material via cyclic voltammetry (CV). The film-like material can be directly electrosynthesized on any conductive substrates and renders the catalyst immobilization step redundant. Through stepwise analysis of deposition voltammograms facilitated by straightforward modification of CV conditions, and characterization using X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS), a two-step mechanism involving the initial WS3 deposition and subsequent partial reduction to WS2 was proposed. The WS2/WS3 material was determined to possess composition of WS2.64. Compared to non electrosynthesized WSx materials, its predominantly basal orientation limited the heterogeneous electron transfer rate toward surface-sensitive redox couples. However, WS2.64 demonstrated excellent HER activity, with the lowest Tafel slope of 43.7 mV dec(-1) to date; this was attributed to different metal-chalcogen binding strengths within WS2.64. Fundamental understanding of the electrosynthesis process is crucial for green syntheses of inexpensive and highly electrocatalytically active materials for sustainable energy production. Albeit, the process may be different for a myriad of nanomaterials, this study can be exploited for its analyses from which the conclusions were made, to empower electrochemical synthesis as the prime fabrication approach for HER electrocatalyst development. PMID- 26844595 TI - Influence of C-H...O Hydrogen Bonds on Macroscopic Properties of Supramolecular Assembly. AB - For CH...O hydrogen bonds in assembled structures and the applications, one of the critical issues is how molecular spatial structures affect their interaction modes as well as how to translate the different modes into the macroscopic properties of materials. Herein, coumarin-derived isomeric hydrogelators with different spatial structures are synthesized, where only nitrogen atoms locate at the ortho, meso, or para position in the pyridine ring. The gelators can self assemble into single crystals and nanofibrous networks through CH...O interactions, which are greatly influenced by nitrogen spatial positions in the pyridine ring, leading to the different self-assembly mechanisms, packing modes, and properties of the nanofibrous networks. Typically, different cell proliferation rates are obtained on the different CH...O bonds driving nanofibrous structures, implying that tiny variation of the stereo-position of nitrogen atoms can be sensitively detected by cells. The study paves a novel way to investigate the influence of isomeric molecular assembly on macroscopic properties and functions of materials. PMID- 26844596 TI - Surveillance of Vaccination Coverage Among Adult Populations - United States, 2014. AB - PROBLEM/CONDITION: Overall, the prevalence of illness attributable to vaccine preventable diseases is greater among adults than among children. Adults are recommended to receive vaccinations based on their age, underlying medical conditions, lifestyle, prior vaccinations, and other considerations. Updated vaccination recommendations from CDC are published annually in the U.S. Adult Immunization Schedule. Despite longstanding recommendations for use of many vaccines, vaccination coverage among U.S. adults is low. REPORTING PERIOD: August 2013-June 2014 (for influenza vaccination) and January-December 2014 (for pneumococcal, tetanus and diphtheria [Td] and tetanus and diphtheria with acellular pertussis [Tdap], hepatitis A, hepatitis B, herpes zoster, and human papillomavirus [HPV] vaccination). DESCRIPTION OF SYSTEM: The National Health Interview Survey (NHIS) is a continuous, cross-sectional national household survey of the noninstitutionalized U.S. civilian population. In-person interviews are conducted throughout the year in a probability sample of households, and NHIS data are compiled and released annually. The survey objective is to monitor the health of the U.S. population and provide estimates of health indicators, health care use and access, and health-related behaviors. RESULTS: Compared with data from the 2013 NHIS, increases in vaccination coverage occurred for Tdap vaccine among adults aged >=19 years (a 2.9 percentage point increase to 20.1%) and herpes zoster vaccine among adults aged >=60 years (a 3.6 percentage point increase to 27.9%). Aside from these modest improvements, vaccination coverage among adults in 2014 was similar to estimates from 2013 (for influenza coverage, similar to the 2012-13 season). Influenza vaccination coverage among adults aged >=19 years was 43.2%. Pneumococcal vaccination coverage among high-risk persons aged 19-64 years was 20.3% and among adults aged >=65 years was 61.3%. Td vaccination coverage among adults aged >=19 years was 62.2%. Hepatitis A vaccination coverage among adults aged >=19 years was 9.0%. Hepatitis B vaccination coverage among adults aged >=19 years was 24.5%. HPV vaccination coverage among adults aged 19-26 years was 40.2% for females and 8.2% for males. Racial/ethnic differences in coverage persisted for all seven vaccines, with higher coverage generally for whites compared with most other groups. Adults without health insurance were significantly less likely than those with health insurance to report receipt of influenza vaccine (aged >=19 years), pneumococcal vaccine (aged 19-64 years with high-risk conditions and aged >=65 years), Td vaccine (aged >=19 years), Tdap vaccine (aged >=19 years and 19-64 years), hepatitis A vaccine (aged >=19 years overall and among travelers), hepatitis B vaccine (aged >=19 years, 19-49 years, and 19-59 years with diabetes), herpes zoster vaccine (aged >=60 years and 60-64 years), and HPV vaccine (females aged 19-26 years and males aged 19-26 years). Adults who reported having a usual place for health care generally were more likely to receive recommended vaccinations than those who did not have a usual place for health care, regardless of whether they had health insurance. Vaccination coverage was significantly higher among those reporting one or more physician contacts in the past year compared with those who had not visited a physician in the past year, regardless of whether they had health insurance. Even among adults who had health insurance and >=10 physician contacts within the past year, 23.8%-88.8% reported not having received vaccinations that were recommended either for all persons or for those with some specific indication. Overall, vaccination coverage among U.S.-born respondents was significantly higher than that of foreign-born respondents with few exceptions (influenza vaccination [adults aged 19-49 years], hepatitis A vaccination [adults aged >=19 years], hepatitis B vaccination [adults with diabetes aged >=60 years], and HPV vaccination [males aged 19-26 years]). INTERPRETATION: Overall, increases in adult vaccination coverage are needed. Although modest gains occurred in Tdap vaccination coverage among adults aged >=19 years and herpes zoster vaccination coverage among adults aged >=60 years, coverage for other vaccines and risk groups did not improve, and racial/ethnic disparities persisted for routinely recommended adult vaccines. Coverage for all vaccines for adults remained low, and missed opportunities to vaccinate adults continued. Although having health insurance coverage and a usual place for health care are associated with higher vaccination coverage, these factors alone do not assure optimal adult vaccination coverage. PUBLIC HEALTH ACTIONS: Assessing associations with vaccination is important for understanding factors that contribute to low coverage rates and to disparities in vaccination, and for implementing strategies to improve vaccination coverage. Practices that have been demonstrated to improve vaccination coverage should be used. These practices include assessment of patients' vaccination indications by health care providers and routine recommendation and offer of needed vaccines to adults, implementation of reminder-recall systems, use of standing-order programs for vaccination, and assessment of practice-level vaccination rates with feedback to staff members. For vaccination to be improved among those least likely to be up-to-date on recommended adult vaccines, efforts also are needed to identify adults who do not have a regular provider or insurance and who report fewer health care visits. PMID- 26844597 TI - Three-dimensional bioprinting of multilayered constructs containing human mesenchymal stromal cells for osteochondral tissue regeneration in the rabbit knee joint. AB - The use of cell-rich hydrogels for three-dimensional (3D) cell culture has shown great potential for a variety of biomedical applications. However, the fabrication of appropriate constructs has been challenging. In this study, we describe a 3D printing process for the preparation of a multilayered 3D construct containing human mesenchymal stromal cells with a hydrogel comprised of atelocollagen and supramolecular hyaluronic acid (HA). This construct showed outstanding regenerative ability for the reconstruction of an osteochondral tissue in the knee joints of rabbits. We found that the use of a mechanically stable, host-guest chemistry-based hydrogel was essential and allowed two different types of extracellular matrix (ECM) hydrogels to be easily printed and stacked into one multilayered construct without requiring the use of potentially harmful chemical reagents or physical stimuli for post-crosslinking. To the best of our knowledge, this is the first study to validate the potential of a 3D printed multilayered construct consisting of two different ECM materials (atelocollagen and HA) for heterogeneous tissue regeneration using an in vivo animal model. We believe that this 3D printing-based platform technology can be effectively exploited for regeneration of various heterogeneous tissues as well as osteochondral tissue. PMID- 26844599 TI - A spiritual arm for community nurses. PMID- 26844598 TI - High-Frequency Ultrasound-Guided Injection for the Generation of a Novel Orthotopic Mouse Model of Human Thyroid Carcinoma. AB - BACKGROUND: Thyroid carcinoma is the most common endocrine malignancy and has an increasing incidence. High-frequency ultrasound (HFUS) has a spatial resolution of 30 MUm, which is a property that has been exploited for thyroid visualization and analysis in mice. The aim of this study was to generate a novel orthotopic mouse model of human follicular thyroid carcinoma (FTC) using an HFUS-guided injection system. METHODS: Twenty Balb/C nude mice were injected in the right lobe of the thyroid with 2 * 10(6) FTC-133 cells using the microinjection HFUS guided system, and 20 mice, used as a control, underwent surgical orthotopic implantation of 2 * 10(6) FTC-133 cells in the right lobe of the thyroid. All mice underwent HFUS imaging two weeks after cell injection; HFUS examinations and tumor volume (TV) measurements were repeated weekly. Micro-computed tomography was performed at different time points to determine whether lung metastasis had occurred. TVs were compared between the two models (surgical vs. HFUS-guided) using the Mann-Whitney U-test, and the Mantel-Cox log-rank test was applied to evaluate the death hazard. Hematoxylin and eosin analysis of formalin-fixed, paraffin-embedded mouse tissue was performed to validate the in vivo imaging results. RESULTS: Of the HFUS-guided injected mice, 9/18 survived up to 40 days after the injection of tumor cells. Mice injected surgically had 100% mortality at day 29. Of 38 mice, 29 (14/18 HFUS, 15/20 surgical) showed metastasis in the salivary glands and lymph nodes, and 13 (10/18 HFUS, 3/20 surgical) also showed metastasis in the lungs, which was confirmed by histological analysis. In the surgical group, there was an evident, frequent (12/20 mice) involvement of the contralateral lobe of the thyroid, whereas this feature was only detected in 1/18 mice in the HFUS group. Statistical analysis showed the same pattern of growth in the two groups, and a significant hazard in the mice in the surgical group (p = 0.03). CONCLUSIONS: This study demonstrated the technical feasibility of an HFUS guided orthotopic mouse model of FTC. The HFUS-guided orthotopic model is easily reproducible and allows prolonged monitoring of the disease because the animals showed an increased survival rate. PMID- 26844600 TI - Parish nursing: a unique resource for community and district nurses. AB - This paper examines the effect of parish nursing as a faith community initiative to support the work of district and community nurses and improve health outcomes. It discusses the reasons why faith communities might embark upon health initiatives, and describes the practice of parish nursing and its history and development in the UK. With reference to both quantitative and qualitative outcomes, the relevance of the practice in the UK health scene is assessed. The paper suggests that connecting with the third sector through parish nursing could enhance the work of community and district nurses; this would present additional sources of holistic care and health promotion and can be offered in an optional but complementary manner to the care provided through the NHS. PMID- 26844601 TI - Use of emollients in the management of atopic eczema. PMID- 26844602 TI - Factors enabling implementation of integrated health and social care: a systematic review. AB - BACKGROUND: In spite of ongoing UK Government recommendations for integrated health and social care, the implementation has been slow. While there are pockets of integration happening across England, many services remain isolated and fragmented. AIM: This review aims to critically review existing evidence to identify if there are any factors enabling successful implementation of integrated health and social care for people with long-term conditions in the community. METHOD: A review was conducted following the principles of a systematic review. Relevant data was extracted from the identified papers and the papers were quality appraised. RESULTS: A total of seven studies were included in the review. Data analysis and synthesis identified a number of themes in relation to enablers of integrated care, including co-location of teams, communication, integrated organisations, management and leadership, capacity and resources, and information technology. CONCLUSION: There is a limited amount of evidence regarding integrated health and social care teams. Although there are some consistencies within the findings, further research is needed to enhance the validity of the body of evidence available. PMID- 26844603 TI - Practical guidance for nurses caring for stoma patients with long-term conditions. AB - As the population ages and the number of people living with a long-term condition grows, it is likely that community nurses may be presented with increasing numbers of people requiring assessment, support, and advice for complex needs. Many of the long-term conditions affect the patient's ability to live and manage aspects of daily life independently and may affect the ability to manage a stoma. The purpose of this article is to consider how long-term conditions affect daily living and stoma care, and make practical suggestions for stoma management. Sources of further help and information for people living with a stoma (ostomates) and a long-term condition have also been included. It is hoped that by reading this article, the nurse will become more familiar with the difficulties with dexterity associated with long-term conditions experienced by ostomates, and how they can be assisted in managing and living as independently as possible. PMID- 26844604 TI - Use of mobile devices in community health care: barriers and solutions to implementation. AB - Mobile devices allow clinicians to access electronic clinical systems away from traditional base locations. They have contributed to increased productivity and efficiency, and clinical staff also cite benefits to patient care. A selection of NHS trusts have participated in a national pilot to explore the benefits and drawbacks of this technology. Clinical engagement with frontline staff is essential to ensure the staff feel valued, listened to, and fully involved to ensure any change to existing practice is successful. Moreover, the training needs of the workforce require careful consideration. The provision of information technology (IT) support services is fundamental to ensure that staff receive the necessary assistance with any functionality issues they may experience with mobile devices to minimise the effect on clinical practice. Variability in internet connectivity may present as a challenge to clinical staff, and the benefits of complimentary offline working solutions should be considered. Barriers to the successful use of mobile devices should be reported as this may have a negative clinical effect on the safe delivery of patient care. Clinical staff need to be mindful of their obligations in relation to information governance, and should appreciate that the same consideration needs to be given to both paper and electronic records. PMID- 26844605 TI - NHSBT consideration to ignore family override of consent to organ donation. AB - NHS Blood and Transplant (NHSBT), the agency responsible for allocating donated organs and maintaining the organ donor register, is considering proceeding with harvesting organs from a registered donor in spite of objections from the deceased's family, in order to raise the number of available organs. District nurses are witness to the need for an increase in the number of donated organs, given the care they provide to those waiting for transplant, and it is essential that district nurses inform this debate. In this article, the author discusses the NHSBT proposal and reviews the law of consent in relation to organ donation. PMID- 26844606 TI - Challenges of loss and grief in palliative care nursing. PMID- 26844607 TI - Community management and pioneering treatments in MS. PMID- 26844608 TI - Improving transitions from hospital to home. PMID- 26844609 TI - Tools of the Trade: Point-of-Care Ultrasonography as a Stethoscope. AB - Since the advent of portable ultrasonography machines, many providers, including intensivists and pulmonologists, have been trained in point-of-care ultrasonography. When point-of-care ultrasonography is performed with focused clinical question and goal in mind, it serves as a valuable adjunct to physical examination and facilitates patient care and disease management. Its clinical application is now wider than that of a stethoscope in the intensive care unit where the noise level is high. In this review article, crucial ultrasonographic findings, their clinical implication, and their limitations are discussed in the most commonly targeted organ systems: cardiac, thoracic, abdominal, and vascular. In addition, recent studies on the use of multiorgan system point-of-care ultrasonography in diagnoses and management of acutely ill patients are described. As new clinical applications have been identified, a conventional approach to the critical illness must be modified to a new approach that incorporates ultrasonographic information. Clinicians should not only be trained in image acquisition and interpretation but also be up to date on the new ultrasonography-guided diagnosis, therapy, and management. PMID- 26844610 TI - Health-related quality of life after laparoscopic sleeve gastrectomy. A multicentric experience. AB - BACKGROUND: Obesity has an impact on health-related quality of life (HRQoL) and bariatric surgery may improve HRQoL in addition to severe obesity-related comorbidities. Aim of the study was to evaluate HRQoL following sleeve gastrectomy and the sensitivity of two HRQoL questionnaires: the Impact of Weight on Quality Of Life-Lite (IWQOL-Lite) and the World Health Organization-Quality Of Life-Bref (WHOQOL-Bref) scales. METHODS: Data were prospectively collected from 149 adult patients submitted to laparoscopic sleeve gastrectomy, before, at 6 and 12 months post-operatively. HRQoL was measured using both the WHOQOL-Bref and the IWQOL-Lite questionnaires. RESULTS: Mean age was 40.5+/-11.9 years, mean initial weight 118.7+/-30.3 kg and mean preoperative Body Mass Index (BMI) was 44.1+/-6.3 kg/m2. Excess weight loss (EWL) was 53.1% and 68.8% respectively at 6 and 12 months postoperatively. Both questionnaires showed significant improvement of HRQoL 12 months after the procedure. Two over 4 domains (physical and psychological health) of the WHOQOL-Bref improved at 6 months whereas all of the 5 domains of the IWQOL-Lite did. The IWQOL-Lite questionnaire pointed out a significant enhancement both at 6 and 12 months. CONCLUSIONS: HRQoL is improved after sleeve gastrectomy. The specific obesity questionnaire IWQOL-Lite seems to be more sensitive than the generic WHOQOL-Bref to detect amelioration of HRQoL. PMID- 26844611 TI - Carcinoma of the Bartholin Gland: A Review of 33 Cases. AB - OBJECTIVE: Primary carcinoma of the Bartholin gland is a rare malignancy that accounts for approximately 5% of vulvar carcinomas. The aim of the study was to compare the outcomes of women with primary Bartholin gland carcinoma (BGC) with those with non-Bartholin gland-related vulvar carcinoma. MATERIALS AND METHODS: A retrospective chart review of 429 patients with invasive vulvar carcinoma evaluated at a single institution between 1993 and 2011 was performed. Medical records were reviewed for demographic data, pathologic information, treatment type, and recurrence/outcome information. These variables were compared between patients with primary BGC and patients with non-Bartholin gland-related vulvar carcinoma. RESULTS: Thirty-three (7.7%) of the 429 patients with invasive vulvar carcinoma had primary carcinoma of the Bartholin gland. Twenty-nine patients (87.9%) had squamous cell histology and 4 patients (12.1%) had adenocarcinoma. When compared with non-Bartholin gland-related vulvar carcinoma, patients with primary BGC had a younger age at diagnosis (median, 57 vs 63 years; P = 0.045), had a higher rate of stage III/IV disease (60.6% vs 35.8%; P = 0.008), and were more likely to receive radiation therapy (78.8% vs 43.9%; P < 0.001). However, there were no significant differences between the 2 groups with regard to histologic subtype, lymphovascular space involvement, perineural invasion, positive margins, recurrence-free survival, or overall survival. CONCLUSIONS: Despite being diagnosed at a more advanced stage, patients with primary carcinoma of the Bartholin gland seem to have similar oncologic outcomes and survival rates to patients with non-Bartholin gland-related vulvar carcinoma. PMID- 26844612 TI - Heated IntraPEritoneal Chemotherapy (HIPEC) for Patients With Recurrent Ovarian Cancer: A Systematic Literature Review. AB - BACKGROUND: Despite advances in surgical oncology, most patients with primary ovarian cancer develop a recurrence that is associated with a poor prognosis. The aim of this review was to establish the impact of Heated IntraPEritoneal Chemotherapy (HIPEC) in the overall survival of patients with recurrent ovarian cancer. METHODS: A search of PubMed/MEDLINE databases was performed in February 2015 using the terms "recurrent ovarian cancer," "cytoreductive surgery/cytoreduction," and "heated/hyperthermic intraperitoneal chemotherapy." Only English articles with available abstracts assessing the impact of HIPEC in patients with recurrent ovarian cancer were examined. The primary outcome measure was overall survival, whereas secondary outcomes included disease-free survival and HIPEC-related morbidity. RESULTS: Sixteen studies with 1168 patients were analyzed. Most studies were Level IV, with 4 studies graded as Level III and 1 Level II. Cisplatin was the main chemotherapeutic agent used, but variations were observed in the actual technique, temperature of perfusate, and duration of treatment. In patients undergoing cytoreductive surgery and HIPEC, the overall survival ranged between 26.7 and 35 months, with disease-free survival varying between 8.5 and 48 months. Heated IntraPEritoneal Chemotherapy seems to confer survival benefits to patients with recurrent disease, with a randomized controlled study reporting that the overall survival is doubled when cytoreductive surgery is compared with cytoreductive surgery and chemotherapy (13. 4 vs 26.7 months). Heated IntraPEritoneal Chemotherapy-related morbidity ranged between 13.6% and 100%, but it was mainly minor and not significantly different from that experienced by patients who only underwent cytoreduction. CONCLUSIONS: Cytoreductive surgery and HIPEC seem to be associated with promising results in patients with recurrent ovarian cancer. Large international prospective studies are required to further quantify the true efficacy of HIPEC and identify the optimal treatment protocol for a maximum survival benefit. PMID- 26844613 TI - Correlations Between Radiation Dose in Bone Marrow and Hematological Toxicity in Patients With Cervical Cancer: A Comparison of 3DCRT, IMRT, and RapidARC. AB - OBJECTIVE: To comparatively evaluate the hematological toxicity (HT) associated with 3 concurrent chemoradiotherapies that are routinely used to treat cervical cancer, including 3-dimensional conformal radiotherapy (3DCRT), intensity modulated radiation therapy (IMRT), and RapidARC and to establish a new normal tissue complication probability model of bone marrow (BM) to predict HT in cervical cancer patients undergoing concurrent chemoradiotherapy. METHODS: Patients with cervical cancer (N = 100) who received concurrent cisplatin and whole-pelvic radiotherapy were enrolled in this study. Dosimetric parameters (including V10, V20, V30, and V40 and mean doses to the pelvic bone) and HT were analyzed. RESULTS: The V20, V30, and V40 and mean doses to the BM were lower in the IMRT and RapidARC groups than in the 3DCRT group, and the RapidARC group had higher V10 and V40 and mean values than the IMRT group. The V20, V30, and V40 and the mean dose to the pelvic bone were positively correlated with HT. Generalized linear normal tissue complication probability models of white blood cell (WBC) and absolute neutrophil cell (ANC) nadirs and BM V20 were established as follows: WBC nadir = 3.382 - 4.056 * V20 + 0.295 * baseline of WBC (adjusted R = 0.246, F = 15.847) and ANC nadir = 2.438 - 2.780 * V20 + 0.233 * baseline of ANC (adjusted R = 0.236, F = 16.282). CONCLUSIONS: This study suggests that IMRT results in milder hematological toxicity than either 3DCRT or RapidARC. Dosimetric parameters were associated with the incidence of HT in cervical cancer patients who received concurrent chemoradiotherapies. PMID- 26844614 TI - Cutaneous Cellular Pseudoglandular Schwannoma: An Unusual Histopathologic Variant. AB - Cellular schwannoma and pseudoglandular schwannoma are both previously described rare variants of schwannoma. The authors present an unusual case of a cellular spindle cell neoplasm with prominent gland-like structures, having features of both variants. The nature of this lesion was confirmed by histology and immunohistochemistry, with diffuse and strong S100 and membranous collagen type IV staining. The gland-like structures were lined by S100 + cells and contained proteinaceous, mucicarmine-negative material, supporting a degenerative, not true glandular, phenomenon. This is the first case of a cutaneous schwannoma demonstrating both marked cellularity and pseudoglandular formation, which the authors have designated cutaneous cellular pseudoglandular schwannoma. Recognition of this extremely rare variant will help avoid diagnostic confusion and overtreatment of this benign entity. PMID- 26844615 TI - Kikuchi-Fujimoto Disease Associated With Subcutaneous Panniculitis-Like T-Cell Lymphoma. AB - Subcutaneous panniculitis-like T-cell lymphoma (SPTL) is a variant of cutaneous T cell lymphoma that can mimic inflammatory panniculitis, particularly lupus erythematosus panniculitis, clinically and histologically. Patients with SPTL generally have a benign course, though SPTL can be complicated by hemophagocytic syndrome, which can negatively impact prognosis. We report a patient with recurrent SPTL and hemophagocytic syndrome accompanied by a necrotizing lymphadenitis consistent with Kikuchi-Fujimoto disease. SPTL and Kikuchi-Fujimoto disease have not previously been reported to occur together, but share many overlapping features. The relationship between these disorders, LE-associated panniculitis, and lupus lymphadenitis deserves further exploration. PMID- 26844616 TI - Hair Follicle Nevus With Features of Comedo Nevus: An Expanding Spectrum. AB - Hair follicle nevus (HFN) is a rare hamartomatous lesion of the folliculosebaceous unit, with or without admixed fibroadipose or muscular tissue. It typically has a congenital presentation in the preauricular area of infants and is frequently confused with an accessory tragus. Acquired tumors with similar histopathologic features have been described infrequently during adolescence and adult life. We report yet another unique presentation of this unusual lesion in a 4-year-old girl who had a long-standing tumor of the nasal columella that started growing rapidly after trauma. Histopathologic examination revealed increased numbers of hair follicles, some of which were associated with diminutive sebaceous glands, with no associated central cystic structure. In addition, the infundibula of the follicles were dilated and filled with keratinous debris. Although these hamartomas are common in the head and neck region, to our knowledge, this is the first report of a HFN at this anatomic location. In addition, this tumor has an overall architecture of a HFN but is accompanied by features of a comedo nevus. We also present a review of the literature and summarize the current diagnostic criteria for HFN. PMID- 26844617 TI - Intralymphatic Proliferation of T-cell Lymphoid Blasts in the Setting of Hidradenitis Suppurativa. AB - Intralymphatic proliferation of T-cell lymphoid blasts (IPTCLBs) is a rare, recently described entity, associated with cutaneous inflammatory conditions and characterized by intralymphatic proliferation of highly proliferating, blastoid T lymphocytes expressing CD30, thus mimicking an intravascular lymphoma. In all reported cases, the intralymphatic proliferation was associated with an underlying inflammatory condition, with no clonal T-cell receptor rearrangement, no signs of systemic or cutaneous lymphoma, and excellent prognosis. The authors present a new case of IPTCLB arising in a patient with hidradenitis suppurativa. Histological examination revealed a dilated follicle embedded within a fibrotic stroma surrounded by a dense lymphoid infiltrate characterized by the presence of dilated small vessels filled with atypical medium-to-large sized blastoid lymphocytes expressing a CD4 T phenotype. There was also expression of CD30, but negativity for cytotoxic markers and Epstein-Barr virus. The proliferation index was high and the vessels showed expression of D2-40, confirming their lymphatic nature. No signs of systemic lymphoma could be detected after routine investigations, and the patient is alive and in good general health. IPTCLB is a rare benign entity that presents with worrying, potentially misleading histopathological features that mimic those observed in intravascular lymphoma. Careful histological and phenotypic investigations and correlation with the clinical features are necessary for a proper diagnosis. PMID- 26844618 TI - Alterations in Hair Follicle Morphology and Hair Shaft Production After Follicular Unit Transplantation. AB - Follicular unit transplantation is the most commonly performed technique in modern restorative hair transplantation surgery. It relies on the acquisition of intact follicular units from microdissected scalp skin strips and their subsequent transplantation into the recipient regions affected by alopecia. Ideally, the translocation of follicular units from the balding-resistant areas of the scalp (usually the occipital region) to the recipient site should not result in any morphological change in the grafts. Nevertheless, the insults associated with surgical intervention present grafted follicles to mechanical and chemical cues differently from those of the physiological steady-state conditions in undamaged skin. This disruption of the normal follicular microenvironment might alter important aspects of hair biology in grafts, for example, hair cycle and pigmentation, and, in turn, could lead to differences in hair appearance, eventually culminating in a diminished esthetical outcome of the surgery. In this study, the authors analyzed native and grafted scalp hair follicles (HFs) from 2 patients who had undergone follicular unit transplantation surgeries formerly. Scanning electron microscopy and light microscopy-based histomorphometry revealed a marked enlargement of follicular structures in the grafts with a concomitant increase in hair shaft diameter. Immunohistological staining confirmed a thickening of the dermal sheath in transplanted HFs that also harbored a denser vascular network. Taken together, these results show that the grafted HFs analyzed were subjected to marked morphological changes during their residence in the recipient site and that this phenomenon is associated with a modulation of follicular vascularization. PMID- 26844619 TI - Hemosiderotic Fibrolipomatous Tumor. PMID- 26844620 TI - Ulcerated Postirradiation Panniculitis After Cardiac Catheterization. PMID- 26844621 TI - Considerations in biomarker development for neurodevelopmental disorders. AB - PURPOSE OF REVIEW: Despite significant progress in recognizing the biological bases of autism spectrum disorder, diagnosis and treatment rely primarily on subjective evaluation of behavior. This review highlights the challenges unique to neurodevelopmental disorders that have limited biomarker development. RECENT FINDINGS: The field of neurodevelopmental disorders requires objective quantification of biological processes to enable designation of subgroups likely to benefit from specific treatments, index diagnostic status/risk, demonstrate engagement of targeted systems, and provide more rapid assessment of change than traditional clinical observation and caregiver report measures. SUMMARY: Useful biomarkers for neurodevelopmental disorders must be reliable across development, evident at the individual level, and specific to a unit of analysis, be it diagnostic status or functional process. The ultimate value of biomarkers for neurodevelopmental disorders will relate to their ease of use, cost, scalability, sensitivity, and methodological objectivity. PMID- 26844622 TI - Doping Status of DHEA Treatment for Female Athletes with Adrenal Insufficiency. AB - OBJECTIVE: To review the doping status of dehydroepiandrosterone (DHEA) for female athletes with adrenal insufficiency within the framework of Therapeutic Use Exemption (TUE) applications for this proandrogen, which is included on the World Anti-Doping Agency (WADA)'s Prohibited List. DATA SOURCES AND MAIN RESULTS: Current knowledge of adrenal pathophysiology with a focus on the physiological role and pharmacological effects of DHEA in female athletes including placebo controlled clinical trials of DHEA and consensus clinical practice and prescribing guidelines. CONCLUSIONS: Because there is no convincing clinical evidence to support the use of DHEA replacement therapy in women with adrenal failure, a TUE for DHEA is not justified by definite health benefit for either secondary or primary adrenal failure. This is consistent with the 2014 update of the US Endocrine Society guidelines, meta-analyses of DHEA treatment in women with or without adrenal failure, current WADA TUE guidance document for adrenal insufficiency and recent case law of WADA's Court of Arbitration for Sport. PMID- 26844623 TI - Iconic gesturing in bonobos. AB - We comment on a recent behavioral study in which we describe a human-like beckoning gesture in 2 groups of bonobos, used in combination with sexual solicitation postures. The beckoning gesture fulfils key criteria of deixis and iconicity, in that it communicates to a distant recipient the desired travel path in relation to a specific social intention, i.e., to have sex at another location. We discuss this finding in light of the fact that, despite the documented great ape capacity and obvious communicative advantage, referential gestures are still surprisingly rare in their natural communication. We address several possibilities for this peculiar underuse and are most compelled by the notion that non-human primates are generally not very motivated to share their experiences of external objects or events with others, which removes most reasons for referential signaling. PMID- 26844624 TI - Direct communication of the spinal subarachnoid space with the rat dorsal root ganglia. AB - The anatomical position of the subarachnoid space (SAS) in relation to dorsal root ganglia (DRG) and penetration of tracer from the SAS into DRG were investigated. We used intrathecal injection of methylene blue to visualize the anatomical position of the SAS in relation to DRG and immunostaining of dipeptidyl peptidase IV (DPP-IV) for detecting arachnoid limiting the SAS. Intrathecal administration of fluorescent-conjugated dextran (fluoro-emerald; FE) was used to demonstrate direct communication between the SAS and DRG. Intrathecal injection of methylene blue and DPP-IV immunostaining revealed that SAS delimited by the arachnoid was extended up to the capsule of DRG in a fold-like recess that may reach approximately half of the DRG length. The arachnoid was found in direct contact to the neuronal body-rich area in the angle between dorsal root and DRG as well as between spinal nerve roots at DRG. Particles of FE were found in the cells of DRG capsule, satellite glial cells, interstitial space, as well as in small and medium-sized neurons after intrathecal injection. Penetration of FE from the SAS into the DRG induced an immune reaction expressed by colocalization of FE and immunofluorescence indicating antigen-presenting cells (MHC-II+), activated (ED1+) and resident (ED2+) macrophages, and activation of satellite glial cells (GFAP+). Penetration of lumbar-injected FE into the cervical DRG was greater than that into the lumbar DRG after intrathecal injection of FE into the cisterna magna. Our results demonstrate direct communication between DRG and cerebrospinal fluid in the SAS that can create another pathway for possible propagation of inflammatory and signaling molecules from DRG primary affected by peripheral nerve injury into DRG of remote spinal segments. PMID- 26844625 TI - Vasa vasorum in the tunica media and tunica adventitia of the porcine aorta. AB - Vasa vasorum supply both the tunica adventitia and the tunica media of major arteries with nutrients and oxygen. We estimated the density of von Willebrand factor-positive profiles of vasa vasorum visible in transversal histological sections of 123 tissue samples collected from five anatomical positions in the porcine aortae of growing pigs (n=25). The animals ranged in age from 0 to 230 days. The tunica media of the thoracic aorta had a greater vasa vasorum density, with microvessels penetrating deeper towards the lumen than in the abdominal aorta. The density of vasa vasorum gradually decreased with age in both the media and the adventitia. The relative depth into which the vasa vasorum penetrated and where they branched remained constant during the ageing and growth of the media. The ratio of the tunica media and tunica adventitia thicknesses did not change in the single aortic segments during ageing. The media of older animals received fewer but equally distributed vasa vasorum. A greater density of vasa vasorum in the media was correlated with greater media thickness and a greater elastin fraction (data on elastin taken from another study on the same samples). Immunohistochemical quantification revealed deeper penetration of vasa vasorum towards the adluminal layers of the tunica media that were hitherto reported to be avascular. The complete primary morphometric data, in the form of continuous variables, have been made available as a supplement. Mapping of the vasa vasorum profile density and position has promising illustrative potential for studies on atherosclerotic and inflammatory neovascularization, aortic aneurysms, and drug distribution from arterial stents in experimental porcine models. PMID- 26844626 TI - Somatostatin supports corneal wound healing in vivo. AB - PURPOSE: To evaluate the influence of somatostatin (SST) and its analog octreotid (Oct) on corneal wound healing processes. METHODS: The wound healing rate in C57BL/6 mice eyes under SST and Oct treatment was analyzed using an alkali induced corneal wounding model. Effects of SST and Oct on cell proliferation, migration and quantified protein expression of vascular endothelial growth factor (VEGF) on human corneal epithelial cells (HCE, cell line) were evaluated by means of electric cell-substrate impedance sensing, scratch migration assays and ELISA. ERK1/2 and p38 phosphorylation was investigated by semi-quantitative western blot analysis. RESULTS: Ten nanograms per microliters of SST significantly accelerated the wound closure rate of corneal defects in vivo. SST and Oct had no influence on HCE cell proliferation and migration and did not activate ERK1/2 or p38 signaling in HCE cells. However, there was increased VEGF protein expression in cytosolic proteins and medium supernatants of HCE upon Oct stimulation for 24h. One and 10ng/ml Oct led to a 2.5-fold and 100ng/ml Oct to a 4-fold upregulation of VEGF protein expression. CONCLUSION: The data implicate that SST promotes corneal wound healing in a mouse model. However, using a HCE cell line in vitro, the wound healing mechanism does not seem to be supported by proliferation and migration processes or by activation of ERK1/2 and p38 signaling pathways. Other possible mechanisms could be the activation of other pathways and the induction of growth factors such as VEGF that modulate the observed corneal wound healing process. PMID- 26844627 TI - Methods of Evidence-Based Anatomy: a guide to conducting systematic reviews and meta-analysis of anatomical studies. AB - Evidence-Based Anatomy (EBA) is the concept of applying evidence-based principles and research methods to the anatomical sciences. While narrative reviews are common in the anatomical sciences, true systematic reviews (SR) and meta-analysis (MA) are only beginning to grow in popularity. In order to enhance the quality of future EBA studies, and ensure the clinical reliability of their results, a uniform methodology is needed. In this paper, we present a step-by-step methodological guide for performing SRs and MAs of anatomical studies. We address the EBA-specific challenges in each step of the SR and MA process, and discuss methods and strategies to overcome these difficulties. Furthermore, we discuss in detail the statistical methods used in MA of anatomical data, including multi categorical and single-categorical pooled prevalence estimates, as well as pooled means of one group. Lastly, we discuss the major limitations of EBA, including the lack of a proper quality assessment tool for anatomical studies. The methods described in this paper present a uniform road map for future EBA studies. PMID- 26844628 TI - Characterization of a beta-catenin nuclear localization defect in MCF-7 breast cancer cells. AB - Beta-catenin plays a key role in transducing Wnt signals from the plasma membrane to the nucleus. Here we characterize an unusual subcellular distribution of beta catenin in MCF-7 breast cancer cells, wherein beta-catenin localizes to the cytoplasm and membrane but atypically did not relocate to the nucleus after Wnt treatment. The inability of Wnt or the Wnt agonist LiCl to induce nuclear localization of beta-catenin was not due to defective nuclear transport, as the transport machinery was intact and ectopic GFP-beta-catenin displayed rapid nuclear entry in living cells. The mislocalization is explained by a shift in the retention of beta-catenin from nucleus to cytoplasm. The reduced nuclear retention is caused by unusually low expression of lymphoid enhancer factor/T cell factor (LEF/TCF) transcription factors. The reconstitution of LEF-1 or TCF4 expression rescued nuclear localization of beta-catenin in Wnt treated cells. In the cytoplasm, beta-catenin accumulated in recycling endosomes, golgi and beta COP-positive coatomer complexes. The peripheral association with endosomes diminished after Wnt treatment, potentially releasing beta-catenin into the cytoplasm for nuclear entry. We propose that in MCF-7 and perhaps other breast cancer cells, beta-catenin may contribute to cytoplasmic functions such as ER golgi transport, in addition to its transactivation role in the nucleus. PMID- 26844629 TI - Inhibition of the myostatin/Smad signaling pathway by short decorin-derived peptides. AB - Myostatin, also known as growth differentiation factor 8, is a member of the transforming growth factor-beta superfamily that has been shown to play a key role in the regulation of the skeletal muscle mass. Indeed, while myostatin deletion or loss of function induces muscle hypertrophy, its overexpression or systemic administration causes muscle atrophy. Since myostatin blockade is effective in increasing skeletal muscle mass, myostatin inhibitors have been actively sought after. Decorin, a member of the small leucine-rich proteoglycan family is a metalloprotein that was previously shown to bind and inactivate myostatin in a zinc-dependent manner. Furthermore, the myostatin-binding site has been shown to be located in the decorin N-terminal domain. In the present study, we investigated the anti-myostatin activity of short and soluble fragments of decorin. Our results indicate that the murine decorin peptides DCN48-71 and 42-65 are sufficient for inactivating myostatin in vitro. Moreover, we show that the interaction of mDCN48-71 to myostatin is strictly zinc-dependent. Binding of myostatin to activin type II receptor results in the phosphorylation of Smad2/3. Addition of the decorin peptide 48-71 decreased in a dose-dependent manner the myostatin-induced phosphorylation of Smad2 demonstrating thereby that the peptide inhibits the activation of the Smad signaling pathway. Finally, we found that mDCN48-71 displays a specificity towards myostatin, since it does not inhibit other members of the transforming growth factor-beta family. PMID- 26844630 TI - Intronic miR-932 targets the coding region of its host gene, Drosophila neuroligin2. AB - Despite great progress for two decades in microRNAs (miRNAs), the direct regulation of host gene by intragenic (mostly intronic) miRNA is conceptually plausible but evidence-limited. Here, we report that intronic miR-932 could target its host gene via binding with coding sequence (CDS) region rather than regular 3'UTR. The conserved miR-932 is embedded in the fourth intron of Drosophila neuroligin2 (dnlg2), which encodes a synaptic cell adhesion molecule, DNlg2. In silico analysis predicted two putative miR-932 target sites locate in the CDS region of dnlg2 instead of regular 3'-UTR miRNA binding sites. Employing luciferase reporter assay, we further proved that the miR-932 regulates expression of its host gene dnlg2 via the binding CDS region of dnlg2. Consistently, we observed miR-932 downregulated expression of dnlg2 in S2 cell, and the repression of dnlg2 by miR-932 at both protein and RNA level. Furthermore, we found CDS-located site1 is dominant for regulating expression of host dnlg2 by miR-932. In addition to providing thorough examination of one intronic miRNA targeting the CDS region of its host gene, our genome-wide analysis indicated that nearly half of fruitfly and human intronic miRNAs may target their own host gene at coding region. This study would be valuable in elucidating the regulation of intronic miRNA on host gene, and provide new information about the biological context of their genomic arrangements and functions. PMID- 26844631 TI - CTRP3 promotes energy production by inducing mitochondrial ROS and up-expression of PGC-1alpha in vascular smooth muscle cells. AB - C1q/tumor necrosis factor-related protein-3 (CTRP3) is an adipokine with modulation effects on metabolism and inflammation. Adenosine triphosphate (ATP) exerts multiple biological effects in vascular smooth muscle cells (VSMCs) and energy imbalance is involved in vascular diseases. This study aimed to explore the effect of CTRP3 on energy production and its underlying mechanism in VSMCs. Our results indicated that exogenous CTRP3 increased ATP synthesis and the protein expression of oxidative phosphorylation (OXPHOS)-related molecules, including peroxisome proliferator-activated receptor-gamma coactivator (PGC) 1alpha, sirtuin-3 (SIRT3), complex I, II, III, and V in cultured VSMCs. Depletion of endogenous CTRP3 by small interfering RNA (siRNA) reduced ATP synthesis and the expression of those molecules. PGC-1alpha knockdown abrogated CTRP3-induced ATP production and OXPHOS-related protein expression. Furthermore, CTRP3 increased mitochondrial reactive oxygen species (ROS) production and mitochondrial membrane potential level. Pretreatment with N-acetyl-L-cysteine, a reactive oxygen species scavenger, and cyanidem-chlorophenylhydrazone, an uncoupler of OXPHOS, suppressed CTRP3-induced ROS production, PGC-1alpha expression and ATP synthesis. In conclusion, CTRP3 modulates mitochondrial energy production through targets of ROS and PGC-1alpha in VSMCs. PMID- 26844632 TI - Male Breast: Clinical and Imaging Evaluations of Benign and Malignant Entities with Histologic Correlation. AB - Breast cancer is an uncommon disease in men. As a result, the diagnosis may not initially be considered. Understanding the common benign and malignant entities affecting the male breast is critical for timely and accurate diagnosis in the primary care setting. Most patients present with a palpable breast mass or pain. The usual etiology is gynecomastia, the most common breast condition in males, but breast cancer must always be excluded through careful imaging evaluation when physical examination findings are suspicious or inconclusive. Imaging of the male breast generally relies on mammography and ultrasound, with mammography employed as the initial imaging modality of choice and ultrasound when a mass is detected or suspected. Here we describe the normal male breast anatomy and present an evaluation algorithm for the male patient with breast signs or symptoms. The most common benign and malignant entities are described. PMID- 26844633 TI - Objectively Measured Physical Activity and Symptoms Change in Knee Osteoarthritis. AB - OBJECTIVE: The study objective was to quantify the association between daily physical activity measured by accelerometer and 1-year changes in symptoms among people with knee osteoarthritis. METHODS: Participants from the Osteoarthritis Initiative had knee radiographs and physical activity assessed using GT1M ActiGraph (Pensacola, FL) uniaxial accelerometers at the 48-month visit. Physical activity was calculated and categorized as tertiles of average daily minutes in light and moderate-to-vigorous activity. Outcomes were 1-year change in symptoms measured by Western Ontario and McMaster Universities scales, including pain, stiffness, and physical function. Adjusted multivariable linear models estimated the relationship between tertiles of light or moderate-to-vigorous physical activity and changes in knee symptoms. RESULTS: Among 1059 participants (55% were women; mean age, 66 +/- 9 years), greater time in light activity was associated with a trend toward declined physical function (P = .01). Greater time in daily moderate-to-vigorous activity also was associated with declined physical function (P = .01) and increased pain (P = .08). None of these average changes in symptoms reached minimally important clinical differences. However, greater daily time in both activities was associated with a higher probability of worsening symptoms among persons with Kellgren-Lawrence grade 4 osteoarthritis. CONCLUSIONS: Objectively measured daily activity was not associated with 1-year symptom improvements among community-dwelling adults with knee osteoarthritis. In those with advanced disease (Kellgren-Lawrence grade 4), greater daily minutes in physical activity were associated with worsening symptoms. How best to implement exercise regimens in persons with advanced knee osteoarthritis to reduce the deleterious impact on symptoms needs to be explored. PMID- 26844634 TI - Orthopedic Manifestations of Ochronosis: Pathophysiology, Presentation, Diagnosis, and Management. AB - Ochronotic arthropathy occurs in patients with alkaptonuria, manifesting first in the intervertebral discs of the lumbar spine, with subsequent degeneration most often observed in the knee, hip, and shoulder joints. Efforts at treatment are targeted at minimizing the damaging effects of the underlying metabolic disorder on the articular cartilage. Vitamin E and N-acetyl cysteine are potential therapies because of their scavenging of free radicals and consequent limitation of oxidative damage to joint tissue. Arthroscopy has been found to be an effective diagnostic tool in cases of suspected ochronosis. Arthroplasty performed in patients with ochronotic arthropathy suggests that the procedure is effective in the alleviation of joint pain and the improvement of mobility. Perioperative management of these patients may require more careful consideration pertinent to the associated comorbidities of this disorder. PMID- 26844635 TI - Biomarkers for Heart Failure: An Update for Practitioners of Internal Medicine. AB - Biomarkers have become an integral part of practicing medicine, especially in heart failure. The natriuretic peptides are commonly used in the evaluation of heart failure, but their role extends beyond diagnosis and includes risk stratification and management of heart failure patients. Newer biomarkers have arrived and are becoming part of routine care of heart failure patients. Both ST2 and high-sensitivity troponin have significant prognostic value for mortality, but also may assist in the titration of medical therapy. Procalcitonin can help guide appropriate antibiotic use in patients with heart failure. The ability to appropriately use and interpret these biomarkers is imperative to the care of heart failure patients, especially as these newer biomarkers become widely used. PMID- 26844636 TI - Exercise Heart Rate Reserve and Recovery as Predictors of Incident Type 2 Diabetes. AB - BACKGROUND: We tested the hypothesis that selected exercise heart rate responses, specifically those providing indices of autonomic dysfunction, may be associated with incident type 2 diabetes in 2231 apparently healthy men with normal baseline fasting glucose levels. METHODS: Heart rate reserve was calculated as the difference between the maximal attained heart rate and the supine resting heart rate, whereas heart rate recovery was defined as the maximal heart rate minus the heart rate measured at 2 minutes of recovery after peak or symptom-limited cardiopulmonary exercise testing. Type 2 diabetes was defined as glycated hemoglobin >6.5% or fasting plasma glucose >126 mg/dL at the follow-up examination. RESULTS: During a median follow-up interval of 5 years, 90 of the 2231 men (4.0%) developed type 2 diabetes. The relative risks of incident type 2 diabetes in men within the lowest quartiles of heart rate reserve and heart rate recovery versus men comprising the highest quartiles of heart rate reserve and heart rate recovery were 2.71 (95% confidence interval, 1.20-6.11) and 2.81 (95% confidence interval, 1.36-5.78) after adjusting for potential confounding variables. Each unit increment (1 beat/min) in heart rate reserve and heart rate recovery was associated with a 2% to 3% decreased incidence of type 2 diabetes. CONCLUSIONS: Exercise heart rate reserve and recovery predicted incidence of type 2 diabetes in healthy men, suggesting that autonomic dysfunction may be associated with an increased likelihood for the development of this cardiometabolic risk factor. PMID- 26844638 TI - Magnetic controlled growing rods for early-onset scoliosis: a 4-year follow-up. AB - BACKGROUND CONTEXT: There have been no studies with medium-term follow-up of magnetic controlled growing rods (MCGRs). PURPOSE: This study aimed to report our single center experience of a magnetic growing rod system with an average of 4 years' follow-up. STUDY DESIGN/SETTING: A retrospective case series was carried out. PATIENT SAMPLE: The sample comprised patients with early-onset scoliosis treated with magnetic controlled growth rods who were operated in 2011. OUTCOME MEASURES: Cobb angle, spinal growth rate, complications, and revision were the outcome measures. METHODS: Clinical case notes and radiographs were reviewed. RESULTS: There were 8 patients (5 dual-rod construct, 3 single-rod construct) who had a minimum of 44 months' follow-up and average of 48 months (44-55 months). Mean age at surgery was 8.2 years (range 3-10). Mean preoperative Cobb angle was 60 degrees (34-94), whereas mean postoperative Cobb angle was 42 degrees (32 63). The average number of extensions was 13.8 (range: 12-20). There were 6 patients (75%) who required 8 revision surgeries: rod problems (N=4), proximal screw pull-out (N=3), and development of proximal junction kyphosis (N=1). All three patients who had single-rod construct underwent revision procedure. Currently, four patients (50%) still have the magnetic rods in situ. The mean duration of MCGR in the patient in the removed group was 39 months (range: 34 46). CONCLUSIONS: Medium-term results of MCGR are not as promising as previously reported early results. Hence, MCGRs should be used with caution. Single-rod constructs should definitely be avoided. The role of MCGRs in revision cases still remains unknown. PMID- 26844637 TI - Nelfinavir targets multiple drug resistance mechanisms to increase the efficacy of doxorubicin in MCF-7/Dox breast cancer cells. AB - Development of multidrug resistance (MDR) remains a significant problem in cancer chemotherapy and underscores the importance of using chemosensitizers. Well known MDR mechanisms include: (i) upregulation of drug-efflux; (ii) increased signaling via AKT; and (iii) decreased apoptosis. Therefore, chemosensitizers should target multiple resistance mechanisms. We investigated the efficacy of nelfinavir (NFV), a clinically approved anti-HIV drug, in increasing doxorubicin (DOX) toxicity in a MDR breast cancer cell line, MCF-7/Dox. As compared to parental MCF-7 cells, the MCF-7/Dox were 15-20 fold more resistant to DOX-induced cytotoxicity at 48 h post-exposure (DOX IC50 = 1.8 MUM vs. 32.4 MUM). Coexposures to NFV could significantly (p < 0.05) decrease DOX-IC50 in MCF-7/Dox cells. Multiple exposures to physiologic concentrations of NFV (2.25 MUM or 6.75 MUM) decreased DOX-IC50 by 21-fold and 50-fold, respectively. Interestingly, although single exposure to NFV transiently induced P-glycoprotein (P-gp) levels, multiple treatments with NFV inhibited both P-gp expression and efflux function, which increased intracellular DOX concentrations. Single exposure to NFV augmented the markers of cell-survival (AKT) and autophagy (LC3-II), whereas multiple exposures enabled suppression of both total AKT (t-AKT) and insulin like growth factor-1 (IGF-1)-induced phosphorylated AKT (p-AKT) levels. Multiple exposures to NFV also resulted in increased unfolded protein response (UPR) transducers, e.g. Grp78, p-PERK, p eIF2alpha, and ATF-4; and endoplasmic reticulum (ER) stress induced death sensors, e.g. CHOP & TRIB-3. Multiple exposures to NFV also abrogated the mitogenic effects of IGF-1. In mice carrying MCF-7/Dox tumor xenografts, intraperitoneal (i.p.) injection of NFV (20 mg/kg/day) and DOX (2 mg/kg/twice/wk) decreased tumor growth more significantly (p < 0.01) than either agent alone. Immunohistochemical (IHC) analysis revealed decreased p-AKT and Ki-67 levels. Thus, NFV overcomes MDR in breast cancer cells and should be tested as an adjunct to chemotherapy. PMID- 26844639 TI - Comparison of different microbial laccases as tools for industrial uses. AB - Laccases from different sources are employed in a number of biotechnological processes, each characterized by specific reaction constraints and thus requiring an enzyme with suitable properties. In order to avoid the bias generated by different assay methodologies, in this work we investigated the main properties of ten laccases from fungi and bacteria under identical conditions. As a general rule, the optimal activity was apparent at pH 3-4 and was lost at pH>=7.0 (all laccases were stable at pH>=7.0); enzymes active at neutral pH values were also identified. For all tested laccases, activity increased with temperature up to 80 degrees C and stability was good at 25 degrees C. Interestingly, laccases insensitive to high salt concentration were identified, this favoring their use in treating waste waters. Indeed, bacterial laccases retained a significant activity in the presence of DMSO (up to 40% final concentration) and of surfactants, suggesting that they can be applied in lignin degradation processes requiring solvents. The available laccases are versatile and satisfy requirements related to different processes. Notably, the recombinant laccase from Bacillus licheniformis favorably compares with the tested enzymes, indicating that it is well suited for different biotechnological applications. PMID- 26844640 TI - Comparative pain reduction of oral non-steroidal anti-inflammatory drugs and opioids for knee osteoarthritis: systematic analytic review. AB - OBJECTIVE: Summarize the comparative effectiveness of oral non-steroidal anti inflammatory drugs (NSAIDs) and opioids in reducing knee osteoarthritis (OA) pain. METHODS: Two reviewers independently screened reports of randomized controlled trials (RCTs), published in English between 1982 and 2015, evaluating oral NSAIDs or opioids for knee OA. Included studies were at least 8 weeks duration, conducted in Western Europe, the Americas, New Zealand, or Australia, and reported baseline and follow-up pain using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain subscale (0-100, 100-worst). Effectiveness was evaluated as reduction in pain, accounting for study dropout and heterogeneity. RESULTS: Twenty-seven treatment arms (nine celecoxib, four non selective NSAIDs [diclofenac, naproxen, piroxicam], eleven less potent opioids [tramadol], and three potent opioids [hydromorphone, oxycodone]) from 17 studies were included. NSAID and opioid studies reported similar baseline demographics and efficacy withdrawal rates; NSAID studies reported lower baseline pain and toxicity withdrawal rates. Accounting for efficacy-related withdrawals, all drug classes were associated with similar pain reductions (NSAIDs: -18; less potent opioids: -18; potent opioids: -19). Meta-regression did not reveal differential effectiveness by drug class but found that study cohorts with a higher proportion of male subjects and worse mean baseline pain had greater pain reduction. Similarly, results of the network meta-analysis did not find a significant difference in WOMAC Pain reduction for the three analgesic classes. CONCLUSION: NSAIDs and opioids offer similar pain relief in OA patients. These data could help clinicians and patients discuss likely benefits of alternative analgesics. PMID- 26844641 TI - Integrating ribosomal promoter vectors that offer a choice of constitutive expression profiles in Leishmania donovani. AB - We have designed a novel series of integrating ribosomal RNA promoter vectors with five incrementally different constitutive expression profiles, covering a 250-fold range. Differential expression was achieved by placing different combinations of synthetic or leishmanial DNA sequences upstream and downstream of the transgene coding sequence in order to modulate pre-mRNA processing efficiency and mRNA stability, respectively. All of the vectors have extensive multiple cloning sites, and versions are available for producing N- or C- terminal GFP fusions at each of the possible relative expression levels. In addition, the modular configuration of the vectors allows drug resistance cassettes and other components to be readily exchanged. In toto, these vectors should be useful additions to the toolkit available for molecular and genetic studies of Leishmania donovani. PMID- 26844643 TI - Comparative analysis of microRNA in schistosomula isolated from non-permissive host and susceptible host. AB - The reed vole Microtus fortis is the only known mammal in which the schistosome is naturally prevented from maturing and schistosome infection does not cause significant pathogenesis. However, the mechanism behind this phenomenon remains unknown. In the present study, Solexa deep sequencing technology was used to carry out high-throughput sequencing and comparative analysis of microRNA (miRNA) between small RNA libraries isolated from 10 days oldschistosomula of M. fortis and BALB/c mice.In total, 10d schistosomula from M. fortis and BALB/c mice yielded 13.37 and 10.84 million reads, respectively, and nearly 39% and 40% of reads could be mapped to selected miRNAs in miRbase. Based on a bioinformatic analysis, we found that most of the miRNAs identified in Schistosoma japonicum were detected in our study. Further analysis revealed that 24 miRNAs were differentially expressed between the schistosomula from the two rodents, of which 21 were down-regulated and three were up-regulated in schistosomula from M. fortis. Also, six novel miRNAs were predicted and identified in this study. Target genes were mapped and filtered by correlating them with differentially expressed genes obtained from S. japonicum oligonucleotide microarray analyses performed in previous studies. miRNAs such as miR-10-3p, miR-10-5p, and miR-2b-5p may affect the growth, differentiation, and metabolism of worms via regulation of the expression of target genes such as enolase, aquaporin, TGF-beta-inducible nuclear protein, and paramyosin. Gene Ontology analysis of the predicted target genes of these six differentially expressed miRNAs revealed that some important biological pathways, such as metabolic processes,glycolysis, and catalytic activity, were involved. The results of this study highlight the function of miRNAs in the development and survival of the schistosome, and provide valuable information to increase our understanding of the regulatory function of miRNAs in schistosome development and host-parasite interactions in a differentially susceptible host environment. PMID- 26844642 TI - Vacuolar protein sorting mechanisms in apicomplexan parasites. AB - The phylum Apicomplexa comprises more than 5000 species including pathogens of clinical and economical importance. These obligate intracellular parasites possess a highly complex endomembrane system to build amongst others three morphologically distinct secretory organelles: rhoptries, micronemes and dense granules. Proteins released by these organelles are essential for invasion and hijacking of the host cell. Due to the complexity of the internal organization of these parasites, a wide panoply of trafficking factors was expected to be required for the correct sorting of proteins towards the various organelles. However, Toxoplasma gondii and other apicomplexan parasites contain only a core set of these factors and several of the vacuolar protein sorting (VPS) homologues found in most eukaryotes have been lost in this phylum. In this review, we will summarise our current knowledge about the role of trafficking complexes in T. gondii, highlighting recent studies focused on complexes formed by VPS proteins. We also present a novel, hypothetical model, suggesting the recycling of parasite membrane and micronemal proteins. PMID- 26844644 TI - Sorafenib and gadolinium co-loaded liposomes for drug delivery and MRI-guided HCC treatment. AB - To improve the poor water solubility of sorafenib and to monitor its distribution and the early feedback effects on its in vivo treatment efficacy in a precise manner, sorafenib (SF) and gadolinium (Gd) co-loaded liposomes (SF/Gd-liposomes) were prepared. The simultaneous imaging and therapy efficacies of the SF/Gd liposomes were tested. The solubility of SF in SF/Gd-liposomes was significantly increased from 0.21 MUg/mL to 250 MUg/mL. The imaging capability of SF/Gd liposomes were tested by in-vitro and the in-vivo imaging ability tests and the results confirmed that SF/Gd-liposomes could be served as an effective contrast agent. The design of SF/Gd-liposomes allowed the MRI-guided in vivo visualization of the delivery and biodistribution of liposome. In the in vivo antitumor studies, SF/Gd-liposomes had better antitumor effects in H22 tumor-bearing mice than SF solution (oral or i.v. administration) (P<0.05). These findings indicated that the SF/Gd-liposomes could be used as the promising nano-carriers for the MRI guided in vivo visualization of the delivery and HCC treatment. PMID- 26844645 TI - Assembly of designed protein scaffolds into monolayers for nanoparticle patterning. AB - The controlled assembly of building blocks to achieve new nanostructured materials with defined properties at different length scales through rational design is the basis and future of bottom-up nanofabrication. This work describes the assembly of the idealized protein building block, the consensus tetratricopeptide repeat (CTPR), into monolayers by oriented immobilization of the blocks. The selectivity of thiol-gold interaction for an oriented immobilization has been verified by comparing a non-thiolated protein building block. The physical properties of the CTPR protein thin biomolecular films including topography, thickness, and viscoelasticity, are characterized. Finally, the ability of these scaffolds to act as templates for inorganic nanostructures has been demonstrated by the formation of well-packed gold nanoparticles (GNPs) monolayer patterned by the CTPR monolayer. PMID- 26844646 TI - In vitro studies on human periodontal ligament stem cell sheets enhanced by enamel matrix derivative. AB - Numerous preclinical and clinical studies have focused on the periodontal regenerative functions of enamel matrix derivative (EMD), a heat-treated preparation derived from enamel matrix proteins (EMPs) of developing porcine teeth. In this study, periodontal ligament (PDL) stem cells (PDLSCs) were isolated, and the effects of EMD on the extracorporeal induction process and the characteristics of PDLSC sheets were investigated for their potential as a more effective stem-cell therapy. EMD-enhanced cell sheets could be induced by complete medium supplemented with 50 MUg/mL vitamin C and 100 MUg/mL EMD. The EMD enhanced cell sheets appeared thicker and more compact than the normal PDLSC sheets, demonstrated more layers of cells (3-7 layers), secreted richer extracellular matrix (ECM), showed varying degrees of increases in mRNA expression of periodontal tissue-specific genes (COL I, POSTN), calcification related genes (RUNX2, OPN, OCN) and a cementum tissue-specific gene (CAP), and possessed a better mineralization ability in terms of osteogenic differentiation in vitro. These EMD-enhanced cell sheets may represent a potential option for stem-cell therapy for PDL regeneration. PMID- 26844647 TI - Socialization characteristics in patients with psychogenic nonepileptic seizures (PNES). AB - OBJECTIVE: The purpose of this study was to describe social behaviors and preferences in adults with psychogenic nonepileptic seizures (PNES) including self-reported use of various socialization mediums (face-to-face and indirect communication) as well as perceived social barriers. METHODS: One hundred forty one consecutive patients with a diagnosis of PNES that was later confirmed through inpatient video-EEG monitoring were administered a questionnaire on the day of their first outpatient appointment. The questionnaire was designed to assess preferences in socialization practices, frequency of interpersonal contact, use of social media, and perceived barriers to socialization. The survey was developed to gain a better understanding of the socialization behaviors and preferences of our patients for the future development of customized activities in our wellness program. RESULTS: Contrary to prevalent assumptions that patients with PNES tend to be socially isolated, our responders reported that they were in fact quite socially connected (72.2% reported daily communication with friends and family via telephone, 68.54% saw relatives in person weekly, 65.28% saw friends weekly, and 51.2% reported using the computer daily to socialize). Facebook was the preferred online social media. Indoor/solitary activities were most common with 57.44% stating that they watch TV/read/use the computer. The primary barriers to socialization that respondents endorsed were driving prohibition and medication side effects. Respondents expressed the greatest interest in online support groups or educational programs (29.46%), office-based support groups (28.57%), and volunteering (23.21%). CONCLUSION: Although it has been speculated that social isolation is a significant problem for patients with PNES, considerable participation in social activities was reported. Characteristics of socialization practices may be more nuanced than first believed. When addressing therapeutic interventions with this group of patients in the future, it might be beneficial to offer both distance-based options as well as face-to-face options for treatment and support depending on age and personal preference. PMID- 26844648 TI - History of psychology. AB - The editor of History of Psychology discusses her plan to vary the journal's content and expand its scope in specific ways. The first is to introduce a "Spotlight" feature, a relatively brief, provocative thought piece that might take one of several forms. Along with this new feature, she hopes further to broaden the journal's coverage and its range of contributors. She encourages submissions on the history of the psy-sciences off the beaten path. Finally, she plans to continue the journal's tradition of special issues, special sections, and essay reviews of two or more important recently published books in the field. (PsycINFO Database Record PMID- 26844649 TI - From secure dependency to attachment: Mary Ainsworth's integration of Blatz's security theory into Bowlby's attachment theory. AB - John Bowlby is generally regarded as the founder of attachment theory, with the help of Mary Ainsworth. Through her Uganda and Baltimore studies Ainsworth provided empirical evidence for attachment theory, and she contributed the notion of the secure base and exploratory behavior, the Strange Situation Procedure and its classification system, and the notion of maternal sensitivity. On closer scrutiny, many of these contributions appear to be heavily influenced by William Blatz and his security theory. Even though Blatz's influence on Ainsworth has been generally acknowledged, this article, partly based on understudied correspondence from several personal archives, is the first to show which specific parts of attachment theory can be traced back directly to Blatz and his security theory. When Ainsworth started working with Bowlby in the 1950s, around the time he turned to evolutionary theory for an explanation of his findings, she integrated much of Blatzian security theory into Bowlby's theory in the making and used her theoretical and practical experience to enrich attachment theory. Even though Blatz is hardly mentioned nowadays, several of his ideas live on in attachment theory. PMID- 26844650 TI - Individual perception and cultural development: Foucault's 1954 approach to mental illness and its history. AB - In his 1954 book Mental Illness and Personality Foucault combines the subjective experience of the mentally ill person with a sociocultural historical approach to mental illness and suggests that there exists a reciprocal connection between individual perception and sociocultural development. This article examines the ramifications of these connections in Foucault's 1954 works and the connection with his later historical works. The article also examines the similarities between Foucault's 1954 thoughts and contemporary intellectual thought, such as those outlined in Maurice Merleau-Ponty's existential phenomenology and in Gaston Bachelard and Georges Canguilhem's historical epistemology. In sum, my study shows that Foucault's historical analysis began long before his 1961 dissertation History of Madness. It also shows that, more than announcing the "death" of the subject, Foucault's historical analysis may have contributed to saving it. PMID- 26844651 TI - Cyclical swings: The bete noire of psychiatry. AB - Progress in psychiatry in the West has been retarded by the proclivity of the discipline to swing violently between 2 approaches to viewing mental illness; that is, emphasizing-to the exclusion of the other-the material-somatic vs the psychical-experiential avenues to knowledge. Each time a shift occurs, the leaders of the new dominant approach emotionally denounce the principles and ideas that came before. We can examine this phenomenon historically by looking at Romantic psychiatry, mid-/late-19th century empirical psychiatry, psychoanalysis, and modern biological psychiatry. Looking at the 2 approaches in treatment today, the gold standard of patient care involves combining empirical/psychological care in 1 person (the psychiatrist) or shared between 2 clinicians working intimately with each other (psychiatrist with psychologist or social worker.) Yet as regards psychiatrists, they are discouraged from paying full attention to the psychological side by the way managed care and third-party payment have combined to remunerate them. Finally, how do we account for the intense swings and denunciations in psychiatry? The author speculates on possible explanations but leaves the question open for her readers. PMID- 26844652 TI - Entrenched reductionisms: The bete noire of psychiatry. AB - Like Hannah Decker, I too deplore the destructive battle of psychosocial and biological reductionisms that has bedeviled psychiatry. When I started my psychiatric training almost 50 years ago, the prevailing model for understanding mental disorders was broadly bio/psycho/social in the grand tradition of Pinel and Freud, brought to and adapted in America by Adolph Meyer. When psychiatry is practiced well, it integrates insights from all the different ways of understanding human nature. Unfortunately, the mental health field has since degenerated into a civil war between the biomedical and psychosocial models with little room for compromise or finding middle ground. The inflexible biological reductionists assume that genes are destiny and that there is a pill for every problem: they take a "mindless" position. The inflexible psychosocial reductionists assume that mental health problems all arise from unpleasant experience: They take a "brainless" position. I have spent a good deal of frustrating time trying to open the minds of extremists at both ends, though rarely making much headway. In my view, however, and where I differ from Decker, the reductionisms do not sort so neatly into alternating historical periods. PMID- 26844653 TI - Comments on "cyclical swings" by Professor Hannah Decker: The underappreciated "solid center" of psychiatry. AB - The history of psychiatry is characterized by some deep ideological and conceptual divisions, as adumbrated in Professor Hannah Decker's essay. However, the schism between "biological" and "psychosocial" models of mental illness and its treatment represents extreme positions among some psychiatrists-not the model propounded by academic psychiatry or its affiliated professional organizations. Indeed, the "biopsycho-social model" (BPSM) developed by Dr. George L. Engel has been, and remains, the foundational model for academic psychiatry, notwithstanding malign market forces that have undermined the BPSM's use in clinical practice. The BPSM is integrally related to "centralizing" and integrative trends in American psychiatry that may be traced to Franz Alexander, Karl Jaspers, and Engel himself, among others. This "Alexandrian-Jaspersian Engelian" tradition is explored in relation to Professor Decker's "cyclical swing" model of psychiatry's history. PMID- 26844654 TI - Professor Decker replies. AB - Replies to comments by Allen Frances (see record 2016-05673-005) and Ronald W. Pies (see record 2016-05673-006) on the article by Hannah Decker (see record 2016 05673-004). Frances' sophisticated fine-tuning of Decker's dichotomies is most welcome. Nevertheless, the impact of reductionism on an era does persist. As for Pies, Decker wishes she could share Pies' hopes for the future of an integrated psychiatry, but we are in a biological period that shows little evidence of becoming inclusive of the psychological and the social. (PsycINFO Database Record PMID- 26844656 TI - The archive of the History of Psychology at the University of Rome, Sapienza. AB - The History of Psychology Archive at the University of Rome, Sapienza was founded in 2008 in the Department of Dynamic and Clinical Psychology. The archive aspires to become an indispensable tool to (a) understand the currents, schools, and research traditions that have marked the path of Italian psychology, (b) focus on issues of general and applied psychology developed in each university, (c) identify experimental and clinical-differential methodologies specific to each lab, (d) reconstruct the genesis and consolidation of psychology institutions and, ultimately, (e) write a "story," set according to the most recent historiographical criteria. The archive is designed according to scholarship on the history of Italian psychology from the past two decades. The online archive is divided into five sections for ease of access. The Sapienza archive is a work in progress and it has plans for expansion. (PsycINFO Database Record PMID- 26844657 TI - Digital methods for the history of psychology: Introduction and resources. AB - At the York University Digital History of Psychology Laboratory, we have been working on projects that explore what digital methodologies have to offer historical research in our field. This piece provides perspective on the history and theory of digital history, as well as introductory resources for those who are curious about incorporating these methods into their own work. (PsycINFO Database Record PMID- 26844658 TI - Interleukin-35 is upregulated in response to influenza virus infection and secondary bacterial pneumonia. AB - Postinfluenza pneumococcal pneumonia is an important cause of global morbidity and mortality. What causes this increased susceptibility is not well elucidated. IL-35 is a newly described cytokine in infectious tolerance. A murine model was established to study postinfluenza pneumococcal pneumonia and evaluate the role of IL-35 in host defense against postinfluenza pneumococcal pneumonia. Pulmonary IL-35 was rapidly up-regulated during murine influenza infection, which was partially mediated by type I IFN-alpha/beta receptor signaling pathway. Secondary pneumococcal infection led to a synergistic IL-35 response in influenza-infected mice. Clinical analysis showed that IL-35 levels were significantly elevated in the patients with influenza infection compared with healthy individuals and influenza infection could induce IL-35 production from human peripheral blood mononuclear cells. These data suggest that IL-35 contributes to the increased susceptibility to secondary pneumococcal pneumonia at least in part by inhibiting the early immune response. PMID- 26844659 TI - Reverse kinetics of angiopoietin-2 and endotoxins in acute pyelonephritis: Implications for anti-inflammatory treatment? AB - Based on former studies showing an antagonism between angiopoietin-2 (Ang-2) and bacterial endotoxins (LPS), we investigated the role of Ang-2 as immunomodulatory treatment. At first, kinetics of circulating LPS in Gram-negative pyelonephritis developing after urinary obstruction was studied. Serum LPS, interleukin (IL)-6 and Ang-2 were measured in 25 patients with acute pyelonephritis and sepsis before and after removal of the obstruction performed either with insertion of a pigtail catheter (n=12) or percutaneous drainage (n=13). At a second stage, Ang-2 was given as anti-inflammatory treatment in 40 rabbits one hour after induction of acute pyelonephritis by ligation of the ureter at the level of pelvo-ureteral junction and upstream bacterial inoculation. Survival was recorded; blood mononuclear cells were isolated and stimulated for the production of tumour necrosis factor-alpha (TNFalpha). The decrease in circulating LPS was significantly greater among patients undergoing drainage than pigtail insertion. This was accompanied by reciprocal changes of Ang-2 and IL-6. Treatment with Ang 2 prolonged survival from Escherichia coli pyelonephritis despite high levels of circulating LPS. When Ang-2 was given as treatment of Pseudomonas aeruginosa pyelonephritis, sepsis-induced decrease of TNFalpha production by circulating mononuclear cells was reversed without an effect on tissue bacterial overgrowth. It is concluded that Ang-2 and LPS follow reverse kinetics in acute pyelonephritis. When given as experimental treatment, Ang-2 prolongs survival through an effect on mononuclear cells. PMID- 26844660 TI - Big data and ophthalmic research. AB - Large population-based health administrative databases, clinical registries, and data linkage systems are a rapidly expanding resource for health research. Ophthalmic research has benefited from the use of these databases in expanding the breadth of knowledge in areas such as disease surveillance, disease etiology, health services utilization, and health outcomes. Furthermore, the quantity of data available for research has increased exponentially in recent times, particularly as e-health initiatives come online in health systems across the globe. We review some big data concepts, the databases and data linkage systems used in eye research-including their advantages and limitations, the types of studies previously undertaken, and the future direction for big data in eye research. PMID- 26844661 TI - Suitability of Tillandsia usneoides and Aechmea fasciata for biomonitoring toxic elements under tropical seasonal climate. AB - Aechmea fasciata was evaluated for the first time as a biomonitor of toxic elements, in comparison to the biomonitoring capacity of Tillandsia usneoides, a well-established biomonitor bromeliad species. Plants of both species were exposed to air pollutants from industrial, urban, and agricultural sources, under the tropical seasonal climate, from June/2011 to April/2013, in five sites of Sao Paulo State, Brazil, for 8 consecutive exposure periods of 12 weeks each. The levels of essential and non-essential elements, including trace metals, were quantified at the end of each exposure. T. usneoides and A. fasciata indicated N, Fe, Zn, Co, Cr, and V as air contaminants in the studied sites, during wet and dry seasons and both species were recommended for qualitative biomonitoring. Concentration levels of N, Ca, S, Fe, Zn, Cu, B, Co, and Ni were significantly higher in T. usneoides than in A. fasciata. However, A. fasciata showed a higher effective retention capacity of Ni, Pb, V, Cu, Fe, Cr, and Co during field exposure, as indicated by the estimate of enrichment factor relative to basal concentrations. This species is more suitable for detecting the atmospheric pollution level of those metals than the T. usneoides. Both species indicated adequately the seasonal differences in the pollution levels of several elements, but T. usneoides presented higher ability for biomonitoring the spatial variations and for indicating more properly the sources of each element in the studied region than the A. fasciata. PMID- 26844662 TI - Evaluation of the effect of tetraethylammonium bromide and chloride on the growth and development of terrestrial plants. AB - Quaternary ammonium salts (QAS), which also include ionic liquids, constitute a vast group of chemical compounds that are increasingly common in the commercial use. This situation may lead to the contamination of the natural environment and may constitute a potential threat to all its elements, including terrestrial higher plants. This paper presents the effect of tetraethylammonium chloride [TEA][Cl] and tetraethylammonium bromide [TEA][Br] on the growth and development of spring barley and common radish. The applied QAS were characterized with phytotoxicity dependent on the concentration of compound and characteristics of the study plants. Spring barley turned out to be highly susceptible plant to the analyzed compounds, which was confirmed by % inhibition of length of plants, root length and fresh weight of plants and by calculated values for EC50, NOEC as well as LOEC. On the contrary, a common radish revealed the resistance to QAS used in the study; although, phytotoxic symptoms were still observed when high concentrations of dry weight of soil were applied (1000, 3000 and 5000 mg/kg). The applied QAS caused oxidative stress symptoms, mainly in spring barley seedlings, which were manifested by decreased assimilation of pigments content, increased hydrogen peroxide (H2O2) and malondialdehyde (MDA) content in plant cells and with a changed activity of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD). PMID- 26844663 TI - The immunotoxicity of aluminum trichloride on rat peritoneal macrophages via beta2-adrenoceptors/cAMP pathway acted by norepinephrine. AB - The previous research found that norepinephrine (NE) enhanced the immunotoxicity of aluminum trichloride (AlCl3) on rat peritoneal macrophages in vitro through activating the beta2-adrenoceptors (beta2-AR)/cAMP pathway. On that basis, the experiment in vivo was conducted in this experiment. Eighty Wistar rats were orally exposed to 0 (control group); 0.4 mg/mL (low-dose group); 0.8 mg/mL (mid dose group) and 1.6 mg/mL (high-dose group) AlCl3 for 120 days, respectively. Aluminum (Al), NE, macrophage migration inhibitory factor (MIF) and tumor necrosis factor-alpha (TNF-alpha) contents in serum, cAMP content, beta2-AR density, mRNA expressions of TNF-alpha, MIF and beta2-AR in rat peritoneal macrophages were examined. These results showed that AlCl3 increased serum Al and NE contents, peritoneal macrophages cAMP content, the density and mRNA expression of the beta2-AR, and decreased serum MIF and TNF-alpha contents, peritoneal macrophages mRNA expressions of MIF and TNF-alpha. Serum NE content was negatively correlated with serum TNF-alpha and MIF contents and peritoneal macrophages mRNA expressions of TNF-alpha and MIF, but positively correlated with cAMP content, density of beta2-AR and mRNA expression of beta2-AR of peritoneal macrophages. It indicated that AlCl3 suppresses peritoneal macrophages function of rats through beta2-AR/cAMP pathway acted by NE. PMID- 26844664 TI - Delay and probability discounting among payday and title loan recipients. AB - Payday and title loans are short-term loans associated with significant economic impact. Behavioral theories of impulsive choice may provide insight into behavioral processes that underlie the propensity to take out payday and title loans. Adults between the ages of 18 and 30 recruited from the community completed delay and probability discounting tasks for hypothetical money as well as measures of substance use. Patterns of discounting were characterized using a hyperbolic decay model and area under the curve. Participants who took out a payday and/or title loan in the past (n=41) exhibited more impulsive choice patterns on the delay discounting task than did those who did not (n=255). Substance use mediated this relationship between payday and title loan retention and delay discounting. These findings suggest potentially important relationships between payday/title loan borrowing, substance use, and delay discounting. PMID- 26844665 TI - IonWorks Barracuda Assay for Assessment of State-Dependent Sodium Channel Modulators. AB - Voltage-gated sodium channels represent important drug targets. The implementation of higher throughput electrophysiology assays is necessary to characterize the interaction of test compounds with several conformational states of the channel, but has presented significant challenges. We describe a novel high throughput approach to assess the effects of test agents on voltage-gated sodium currents. The multiple protocol mode of the automated electrophysiology instrument IonWorks Barracuda was used to control the level of inactivation and monitor current stability. Good temporal stability of currents and spatial uniformity of inactivation were obtained by optimizing the experimental conditions. The resulting assay allowed for robust assessment of state-dependent effects of test agents and enabled direct comparison of compound potency across several sodium channel subtypes at equivalent levels of inactivation. PMID- 26844667 TI - Total Synthesis of the 7,10-Epimer of the Proposed Structure of Amphidinolide N, Part I: Synthesis of the C1-C13 Subunit. AB - Amphidinolide N, the structure of which has been recently revised, is a 26 membered macrolide featuring allyl epoxide and tetrahydropyran moieties with 13 chiral centers. Due to its challenging structure and extraordinary potent cytotoxicity, amphidinolide N is a highly attractive target of total synthesis. During our total synthesis studies of the 7,10-epimer of the proposed structure of amphidinolide N, we have synthesized the C1-C13 subunit enantio- and diastereoselectively. Key reactions include an l-proline catalyzed enantioselective intramolecular aldol reaction, Evans aldol reaction, Sharpless asymmetric epoxidation and Tamao-Fleming oxidation. To aid late-stage manipulations, we also developed the 4-(N-benzyloxycarbonyl-N-methylamino)butyryl group as a novel ester protective group for the C9 alcohol. PMID- 26844668 TI - Synthesis of Enantioenriched Indolines by a Conjugate Addition/Asymmetric Protonation/Aza-Prins Cascade Reaction. AB - A conjugate addition/asymmetric protonation/aza-Prins cascade reaction has been developed for the enantioselective synthesis of fused polycyclic indolines. A catalyst system generated from ZrCl4 and 3,3'-dibromo-BINOL enables the synthesis of a range of polycyclic indolines in good yields and with high enantioselectivity. A key finding is the use of TMSCl and 2,6-dibromophenol as a stoichiometric source of HCl to facilitate catalyst turnover. This transformation is the first in which a ZrCl4 ?BINOL complex serves as a chiral Lewis-acid assisted Bronsted acid. PMID- 26844666 TI - Physical exercise increases adult hippocampal neurogenesis in male rats provided it is aerobic and sustained. AB - KEY POINTS: Aerobic exercise, such as running, enhances adult hippocampal neurogenesis (AHN) in rodents. Little is known about the effects of high intensity interval training (HIT) or of purely anaerobic resistance training on AHN. Here, compared with a sedentary lifestyle, we report a very modest effect of HIT and no effect of resistance training on AHN in adult male rats. We found the most AHN in rats that were selectively bred for an innately high response to aerobic exercise that also run voluntarily and increase maximal running capacity. Our results confirm that sustained aerobic exercise is key in improving AHN. ABSTRACT: Aerobic exercise, such as running, has positive effects on brain structure and function, such as adult hippocampal neurogenesis (AHN) and learning. Whether high-intensity interval training (HIT), referring to alternating short bouts of very intense anaerobic exercise with recovery periods, or anaerobic resistance training (RT) has similar effects on AHN is unclear. In addition, individual genetic variation in the overall response to physical exercise is likely to play a part in the effects of exercise on AHN but is less well studied. Recently, we developed polygenic rat models that gain differentially for running capacity in response to aerobic treadmill training. Here, we subjected these low-response trainer (LRT) and high-response trainer (HRT) adult male rats to various forms of physical exercise for 6-8 weeks and examined the effects on AHN. Compared with sedentary animals, the highest number of doublecortin-positive hippocampal cells was observed in HRT rats that ran voluntarily on a running wheel, whereas HIT on the treadmill had a smaller, statistically non-significant effect on AHN. Adult hippocampal neurogenesis was elevated in both LRT and HRT rats that underwent endurance training on a treadmill compared with those that performed RT by climbing a vertical ladder with weights, despite their significant gain in strength. Furthermore, RT had no effect on proliferation (Ki67), maturation (doublecortin) or survival (bromodeoxyuridine) of new adult-born hippocampal neurons in adult male Sprague Dawley rats. Our results suggest that physical exercise promotes AHN most effectively if the exercise is aerobic and sustained, especially when accompanied by a heightened genetic predisposition for response to physical exercise. PMID- 26844669 TI - Surgical treatment strategy for diabetic forefoot osteomyelitis. AB - The aim of this study was to propose an appropriate surgical treatment for diabetic forefoot osteomyelitis (DFO) involving ischemia or moderate to severe soft tissue infection. The records of 28 patients with osteomyelitis from 2009 to 2015 were retrospectively studied. All patients had undergone surgery based on preoperative magnetic resonance imaging examinations and histopathological or culture analyses confirming the surgical bone margin. The appropriate surgical margin, crucial factors for early healing, and prognosis after complete resection of osteomyelitis were examined. After healing, patients were followed up to assess prognosis (range 32-1,910 days, median 546 days). The healing rate of nonischemic cases of DFO with negative surgical margins was 100% and that of ischemic cases was 84.6%; the ambulatory rates for both types of cases were 100%. No wound (and/or osteomyelitis) recurrence was observed. Nine new cases of DFO developed in six patients (21.4%; eight were due to vascular stenosis, and one was due to biomechanical changes in the foot. After complete resection of osteomyelitis, preoperative and postoperative C-reactive protein levels and the size of the ulcer were significant predictors of early healing (p < 0.05, 0.01, and 0.05, respectively). The appropriate surgical margin should be set in the area of bone marrow edema, based on magnetic resonance imaging examinations after revascularization. In cases with high preoperative or postoperative C-reactive protein levels, long-term antibiotic therapy is recommended, and surgery should be planned after the C-reactive protein levels decrease, except in emergencies. PMID- 26844671 TI - Editorial: Transforming biotechnology with synthetic biology. AB - Synthetic biology has advanced to contain not only whole cell systems but also cell-free systems. Combined with minimized genome and promoter engineering, synthetic biology can be used to engineer living systems or biomolecular components for production of chemicals, materials or pharmaceutics. The future looks bright! PMID- 26844672 TI - Meeting Report: Cold Spring Harbor Asia Synthetic Biology Meeting. PMID- 26844673 TI - Lung Quality and Utilization in Controlled Donation After Circulatory Determination of Death Within the United States. AB - Although controlled donation after circulatory determination of death (cDCDD) could increase the supply of donor lungs within the United States, the yield of lungs from cDCDD donors remains low compared with donation after neurologic determination of death (DNDD). To explore the reason for low lung yield from cDCDD donors, Scientific Registry of Transplant Recipient data were used to assess the impact of donor lung quality on cDCDD lung utilization by fitting a logistic regression model. The relationship between center volume and cDCDD use was assessed, and the distance between center and donor hospital was calculated by cDCDD status. Recipient survival was compared using a multivariable Cox regression model. Lung utilization was 2.1% for cDCDD donors and 21.4% for DNDD donors. Being a cDCDD donor decreased lung donation (adjusted odds ratio 0.101, 95% confidence interval [CI] 0.085-0.120). A minority of centers have performed cDCDD transplant, with higher volume centers generally performing more cDCDD transplants. There was no difference in center-to-donor distance or recipient survival (adjusted hazard ratio 1.03, 95% CI 0.78-1.37) between cDCDD and DNDD transplants. cDCDD lungs are underutilized compared with DNDD lungs after adjusting for lung quality. Increasing transplant center expertise and commitment to cDCDD lung procurement is needed to improve utilization. PMID- 26844675 TI - Signaling by the heavy-metal sensor CusS involves rearranged helical interactions in specific transmembrane regions. AB - Two-component systems (TCSs) play important roles in the adaptation of bacteria to stress. Despite their increasingly well understood mechanistic features, it remains poorly understood how TCSs transduce signals across membranes. Here, we use the E. coli Cu/Ag-responsive CusSR TCS as a model to investigate the roles of CusS transmembrane (TM) residues. Proline scanning of TM1 domain led to identification of the T17P, F18P, and S21P variants, which display higher kinase activities relative to wild type. A single point mutation, V202G, in the adjacent TM2 domain specifically suppresses the hyperactivities of these mutants. Disulfide crosslinking analysis demonstrated that T17 and V202 are situated in close proximity, and Cys residues substituted at those two positions form exclusive intramolecular crosslinks when CusS is in the signaling-inactive state. In the signaling-active variant of CusS, however, only intermolecular crosslinking between the two Cys residues could be observed, suggesting that destabilization of an intramolecular constraint and a subsequent rearrangement of helical interactions in this TM region is involved in the activation of CusS. An analogous TM helical interface in the P. aeruginosa heavy metal sensor kinase CzcS is also observed. Together, these results suggested a conserved transmembrane signal transduction mechanism in the heavy metal sensing TCSs. PMID- 26844674 TI - Protease-activated receptor 4: from structure to function and back again. AB - Protease-activated receptors are a family of four GPCRs (PAR1-PAR4) with a number of unique attributes. Nearly two and a half decades after the discovery of the first PAR, an antagonist targeting this receptor has been approved for human use. The first-in-class PAR1 antagonist, vorapaxar, was approved for use in the USA in 2014 for the prevention of thrombotic cardiovascular events in patients with a history of myocardial infarction or with peripheral arterial disease. These recent developments indicate the clinical potential of manipulating PAR function. While much work has been aimed at uncovering the function of PAR1 and, to a lesser extent, PAR2, comparatively little is known regarding the pharmacology and physiology of PAR3 and PAR4. Recent studies have begun to develop the pharmacological and genetic tools required to study PAR4 function in detail, and there is now emerging evidence for the function of PAR4 in disease settings. In this review, we detail the discovery, structure, pharmacology, physiological significance and therapeutic potential of PAR4. Linked Articles This article is part of a themed section on Molecular Pharmacology of G Protein-Coupled Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc. PMID- 26844676 TI - Xp11 neoplasm with melanocytic differentiation of the prostate harbouring the novel NONO-TFE3 gene fusion: report of a unique case expanding the gene fusion spectrum. AB - Recently, an increasing number of TFE3 rearrangement-associated tumours have been reported, such as TFE3 rearrangement-associated perivascular epithelioid cell tumours (PEComas), melanotic Xp11 translocation renal cancers and melanotic Xp11 neoplasms. We have suggested that these tumours belong to a single clinicopathological spectrum. 'Xp11 neoplasm with melanocytic differentiation' or 'melanotic Xp11 neoplasm' have been proposed to designate this unique neoplasm. Herein, we describe the first case of an Xp11 neoplasm with melanocytic differentiation to be described in the prostate, bearing the novel NONO-TFE3 gene fusion. This study both adds to the spectrum regarding melanotic Xp11 neoplasms and expands its gene fusion spectrum. Moreover, we discuss the relationship of these rare tumours to neoplasms such as conventional PEComas, alveolar soft part sarcomas, malignant melanomas, clear cell sarcomas and Xp11 translocation renal cancers. PMID- 26844683 TI - Clues to management of neonatally diagnosed BTK deficiency. PMID- 26844684 TI - Composite System of Graphene Oxide and Polypeptide Thermogel As an Injectable 3D Scaffold for Adipogenic Differentiation of Tonsil-Derived Mesenchymal Stem Cells. AB - As two-dimensional (2D) nanomaterials, graphene (G) and graphene oxide (GO) have evolved into new platforms for biomedical research as biosensors, imaging agents, and drug delivery carriers. In particular, the unique surface properties of GO can be an important tool in modulating cellular behavior and various biological sequences. Here, we report that a composite system of graphene oxide/polypeptide thermogel (GO/P), prepared by temperature-sensitive sol-to-gel transition of a GO suspended poly(ethylene glycol)-poly(L-alanine) (PEG-PA) aqueous solution significantly enhances the expression of adipogenic biomarkers, including PPAR gamma, CEBP-alpha, LPL, AP2, ELOVL3, and HSL, compared to both a pure hydrogel system and a composite system of G/P, graphene-incorporated hydrogel. We prove that insulin, an adipogenic differentiation factor, preferentially adhered to GO, is supplied to the incorporated stem cells in a sustained manner over the three dimensional (3D) cell culture period. On the other hand, insulin is partially denatured in the presence of G and interferes with the adipogenic differentiation of the stem cells. The study suggests that a 2D/3D composite system is a promising platform as a 3D cell culture matrix, where the surface properties of 2D materials in modulating the fates of the stem cells are effectively transcribed in a 3D culture system. PMID- 26844685 TI - Technology Access and Smartphone App Preferences for Medication Adherence in Adolescents and Young Adults With Sickle Cell Disease. AB - BACKGROUND: Hydroxyurea is the only Food and Drug Administration approved medication for sickle cell disease (SCD) with short- and long-term benefits for both morbidity and mortality. However, hydroxyurea underutilization and adherence remain challenges for patients with SCD. The objectives of this study were to determine access to technology among adolescents and young adults (AYA) with SCD and to identify their preferred technology-based strategies for improving medication adherence. PROCEDURE: A cross-sectional survey was administered in a variety of clinical settings from October 2014 through May 2015 to AYA (12-22 years) with SCD (all genotypes) followed in a Comprehensive Sickle Cell Program. RESULTS: Eighty of 107 eligible participants completed the survey for a 75% response rate. Participants (51% female, 94% Black) had a mean age of 15.3 +/- 2.8 years. Most participants (75%) were on a daily medication with about half on hydroxyurea. Forgetfulness (67%) was the most common barrier to medication adherence. The majority of participants (85%) owned smartphones and either owned or had access to electronic tablets (83%), laptops (72%), or desktops (70%). Of the proposed smartphone app features, daily medication reminders were ranked first most frequently, followed by education about SCD, adherence text prompts, education about SCD medications, and medication log. CONCLUSIONS: The majority of our AYA with SCD owned smartphones and had access to other electronic devices. Our survey results provided valuable insight into the preferred app features and optimal strategies for developing technology-based interventions, such as a multicomponent app, to increase medication adherence for AYA with SCD or other chronic conditions. PMID- 26844686 TI - Exacerbation of macular oedema associated with hyperbaric oxygen therapy. PMID- 26844687 TI - Orthovoltage for basal cell carcinoma of the head and neck: Excellent local control and low toxicity profile. AB - OBJECTIVES/HYPOTHESIS: Evaluation of treatment results of orthovoltage X-rays for a selection of previously untreated favorable basal cell carcinomas (BCC) in the head and neck area concerning local control, cosmetic and functional outcome, and toxicity profile. METHODS: A consecutive series of patients with primarily treated BCCs who were irradiated by means of orthovoltage X-rays in the Netherlands Cancer Institute in Amsterdam between January 2000 and February 2015 were retrospectively evaluated. RESULTS: Two hundred fifty-three BCCs in 232 patients were primarily treated with orthovoltage X-rays. The local control rates at 1, 3, and 5 years for this selection of basal cell carcinomas were 98.9%, 97.5%, and 96.3%, respectively. Tumor size was the only significant predictor for local control because BCCs < 20 mm had a significantly higher 5-year local control rate than lesions >= 20 mm (96.8% vs. 89.4%, P = 0.041). Acute toxicity healed spontaneously without medical intervention, and late toxicity rates were low. Functional impairments were negligible, and the cosmetic outcome was excellent. CONCLUSION: Orthovoltage therapy for well-selected favorable BCCs in the head and neck area resulted in excellent local control rates, a low toxicity profile, and apparently satisfactory functional and cosmetic outcomes. Orthovoltage irradiation is a good alternative for surgery for BCCs with favorable histologic prognosis at locations that are at risk for postoperative functional or cosmetic changes, such as the nose or canthus. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1796-1802, 2016. PMID- 26844688 TI - Effect of Low Dose Oral Vitamin-D and Calcium Replacement in HIV Patients. AB - BACKGROUND: There is high prevalence of vitamin-D deficiency and abnormal bone mineral density (BMD) in HIV patients. Our aim is to find out the effect of replacement of low dose oral vitamin-D (800 International unit) with calcium (500mg) as a once daily regimen along with antiretroviral (ARV) on serum vitamin D and parathyroid hormone (PTH) level and bone mineral density (BMD) changes on patients with HIV infection who have vitamin- D deficiency. METHODS: This is a non-randomised, open label study. We collected information about demography, viral load, CD-4 count, fracture risk factors. We measured serum 25(OH)D, parathyroid hormone (intact PTH), inorganic phosphate, corrected calcium, alkaline phosphatase (ALP) and BMD of hip and spine at baseline and after 12 months of routine follow up. Patients were treatment experienced and were divided into tenofovir containing, efavirenz containing, and protease Inhibitor (PI) containing regimens. RESULTS: The study included 87 treatment experienced HIV patients with mean age 42.8 (+/-7.8) years, 55 (63%) females, 73 (84%) black African ethnicity, CD4 count 451.7 (+/-184.6) cells/dL, plasma VL 1.6 log (+/ 0.03) copies/mL, exposure to antiretroviral therapy 43.2 (+/-30.2) months and duration of illness 58.4 (+/- 24.1) months. Forty four patients agreed to take vitamin-D with calcium replacement and 43 patients did not agree to take the replacement. After 12 months of follow up patients on vitamin D and calcium replacement (n=44) had significant increase in vitamin-D level (15.4+/-6.2 vs. 55.9+/-22.6, p=0.0001), reduction in PTH (8.04 +/-7.5, vs. 4.7 +/-1.8, p=0.005), alkaline phosphatase (111.1 +/-79.1 vs. 90.2+/-42.2, p=0.038) and increase in corrected calcium (2.18 +/-0.09 vs. 2.19 +/-0.09 p=0.001). In patients not on vitamin-D replacement (n=43), there was increase in vitamin-D (16.9 +/-12.1 vs. 49.4 +/-29.2, p=0.001) and corrected calcium (2.12 +/-0.09 vs. 2.16 +/-0.08 p=0.0001) level, but PTH and ALP did not change. BMD of hip and spine did not show any significant change in either of the two groups. In multivariate analysis that included all significant variables, vitamin-D and calcium replacement independently was associated with increase in vitamin-D level (OR 1.07, CI 1.02, 1.12, p=0.005), decrease in PTH level (OR 0.53, CI 0.35, 0.82, p=0.004), but not with change in corrected calcium, alkaline phosphatase, BMD of hip or spine. CONCLUSION: After 12 months of follow up, replacement of low dose once daily oral vitamin-D with calcium in treatment experienced HIV patients with vitamin-D deficiency can increase vitamin-D level, reduce PTH level without any change in BMD of hip and spine. PMID- 26844689 TI - Development of Heat Shock Protein (Hsp90) Inhibitors To Combat Resistance to Tyrosine Kinase Inhibitors through Hsp90-Kinase Interactions. AB - Heat shock protein 90 (Hsp90) is a ubiquitous chaperone of all of the oncogenic tyrosine kinases. Many Hsp90 inhibitors, alone or in combination, have shown significant antitumor efficacy against the kinase-positive naive and mutant models. However, clinical trials of these inhibitors are unsuccessful due to insufficient clinical benefits and nonoptimal safety profiles. Recently, much progress has been reported on the Hsp90-cochaperone-client complex, which will undoubtedly assist in the understanding of the interactions between Hsp90 and its clients. Meanwhile, Hsp90 inhibitors have shown promise against patients' resistance caused by early generation tyrosine kinase inhibitors (TKIs), and at least 13 Hsp90 inhibitors are being reevaluated in the clinic. In this regard, the objectives of the current perspective are to summarize the structure and function of the Hsp90-cochaperone-client complex, to analyze the structural and functional insights into the Hsp90-client interactions to address several existing unresolved problems with Hsp90 inhibitors, and to highlight the preclinical and clinical studies of Hsp90 inhibitors as an effective treatment against resistance to tyrosine kinase inhibitors. PMID- 26844690 TI - What is your diagnosis? Hepatomegaly in a cat. PMID- 26844691 TI - Synthesis of alpha-C-Galactosylceramide via Diastereoselective Aziridination: The New Immunostimulant 4'-epi-C-Glycoside of KRN7000. AB - A new immunostimulant, the 4'-epimer of alpha-C-GalCer, was synthesized from a C2 symmetric dienediol and alpha-C-allyl galactoside. The intramolecular aziridination and the following reductive ring opening provided the core of the aliphatic amino alcohol with excellent regio- and stereocontrol. The new immunostimulants 3d and 3e gave a better polarized Th1-type cytokine response in murine NKT cells than the benchmarked alpha-C-GalCer. PMID- 26844692 TI - Polyamine/Nucleotide Coacervates Provide Strong Compartmentalization of Mg2+, Nucleotides, and RNA. AB - Phase separation of aqueous solutions containing polyelectrolytes can lead to formation of dense, solute-rich liquid droplets referred to as coacervates, surrounded by a dilute continuous phase of much larger volume. This type of liquid-liquid phase separation is thought to help explain the appearance of polyelectrolyte-rich intracellular droplets in the cytoplasm and nucleoplasm of extant biological cells and may be relevant to protocellular compartmentalization of nucleic acids on the early Earth. Here we describe complex coacervates formed upon mixing the polycation poly(allylamine) (PAH, 15 kDa) with the anionic nucleotides adenosine 5'-mono-, di-, and triphosphate (AMP, ADP, and ATP). Droplet formation was observed over a wide range of pH and MgCl2 concentrations. The nucleotides themselves as well as Mg(2+) and RNA oligonucleotides were all extremely concentrated within the coacervates. Nucleotides present at just 2.5 mM in bulk solution had concentrations greater than 1 M inside the coacervate droplets. A solution with a total Mg(2+) concentration of 10 mM had 1-5 M Mg(2+) in the coacervates, and RNA random sequence (N54) partitioned ~10,000-fold into the coacervates. Coacervate droplets are thus rich in nucleotides, Mg(2+), and RNA, providing a medium favorable for generating functional RNAs. Compartmentalization of nucleotides at high concentrations could have facilitated their polymerization to form oligonucleotides, which preferentially accumulate in the droplets. Locally high Mg(2+) concentrations could have aided folding and catalysis in an RNA world, making coacervate droplets an appealing platform for exploring protocellular environments. PMID- 26844693 TI - Spectroscopic Evidence for a 3d(10) Ground State Electronic Configuration and Ligand Field Inversion in [Cu(CF3)4](1-). AB - The contested electronic structure of [Cu(CF3)4](1-) is investigated with UV/visible/near IR spectroscopy, Cu K-edge X-ray absorption spectroscopy, and 1s2p resonant inelastic X-ray scattering. These data, supported by density functional theory, multiplet theory, and multireference calculations, support a ground state electronic configuration in which the lowest unoccupied orbital is of predominantly trifluoromethyl character. The consensus 3d(10) configuration features an inverted ligand field in which all five metal-localized molecular orbitals are located at lower energy relative to the trifluoromethyl-centered sigma orbitals. PMID- 26844694 TI - "My Life Needs Editing" (Mort Sahl) and Genome Editing Needs Ethics. PMID- 26844695 TI - Janus Silver-Mesoporous Silica Nanocarriers for SERS Traceable and pH-Sensitive Drug Delivery in Cancer Therapy. AB - A facile and cheap strategy was used to fabricate the novel Janus silver mesoporous silica nanoparticles with excellent SPR and mesoporous properties for simultaneous SERS imaging and pH-responsive drug release, leading to the efficient cancer theranostic with less toxic effects. PMID- 26844696 TI - FGF1 C-terminal domain and phosphorylation regulate intracrine FGF1 signaling for its neurotrophic and anti-apoptotic activities. AB - Fibroblast growth factor 1 (FGF1) is a prototypic member of the FGFs family overexpressed in various tumors. Contrarily to most FGFs, FGF1 lacks a secretion peptide signal and acts mainly in an intracellular and nuclear manner. Intracellular FGF1 induces cell proliferation, differentiation and survival. We previously showed that intracellular FGF1 induces neuronal differentiation and inhibits both p53- and serum-free-medium-induced apoptosis in PC12 cells. FGF1 nuclear localization is required for these intracellular activities, suggesting that FGF1 regulates p53-dependent apoptosis and neuronal differentiation by new nuclear pathways. To better characterize intracellular FGF1 pathways, we studied the effect of three mutations localized in the C-terminal domain of FGF1 (i.e., FGF1(K132E), FGF1(S130A) and FGF1(S130D)) on FGF1 neurotrophic and anti-apoptotic activities in PC12 cells. The change of the serine 130 to alanine precludes FGF1 phosphorylation, while its mutation to aspartic acid mimics phosphorylation. These FGF1 mutants kept both a nuclear and cytosolic localization in PC12 cells. Our study highlights for the first time the role of FGF1 phosphorylation and the implication of FGF1 C-terminal domain on its intracellular activities. Indeed, we show that the K132E mutation inhibits both the neurotrophic and anti-apoptotic activities of FGF1, suggesting a regulatory activity for FGF1 C terminus. Furthermore, we observed that both FGF1(S130A) and FGF1(S130D) mutant forms induced PC12 cells neuronal differentiation. Therefore, FGF1 phosphorylation does not regulate FGF1-induced differentiation of PC12 cells. Then, we showed that only FGF1(S130A) protects PC12 cells against p53-dependent apoptosis, thus phosphorylation appears to inhibit FGF1 anti-apoptotic activity in PC12 cells. Altogether, our results show that phosphorylation does not regulate FGF1 neurotrophic activity but inhibits its anti-apoptotic activity after p53 dependent apoptosis induction, giving new insight into the poorly described FGF1 intracrine/nuclear pathway. The study of nuclear pathways could be crucial to identify key regulators involved in neuronal differentiation, tumor progression and resistances to radio- and chemo-therapy. PMID- 26844697 TI - ANP32B deficiency impairs proliferation and suppresses tumor progression by regulating AKT phosphorylation. AB - The acidic leucine-rich nuclear phosphoprotein 32B (ANP32B) is reported to impact normal development, with Anp32b-knockout mice exhibiting smaller size and premature aging. However, its cellular and molecular mechanisms, especially its potential roles in tumorigenesis, remain largely unclear. Here, we utilize 'knockout' models, RNAi silencing and clinical cohorts to more closely investigate the role of this enigmatic factor in cell proliferation and cancer phenotypes. We report that, compared with Anp32b wild-type (Anp32b(+/+)) littermates, a broad panel of tissues in Anp32b-deficient (Anp32b(-/-)) mice are demonstrated hypoplasia. Anp32b(-/-) mouse embryo fibroblast cell has a slower proliferation, even after oncogenic immortalization. ANP32B knockdown also significantly inhibits in vitro and in vivo growth of cancer cells by inducing G1 arrest. In line with this, ANP32B protein has higher expression in malignant tissues than adjacent normal tissues from a cohort of breast cancer patients, and its expression level positively correlates with their histopathological grades. Moreover, ANP32B deficiency downregulates AKT phosphorylation, which involves its regulating effect on cell growth. Collectively, our findings suggest that ANP32B is an oncogene and a potential therapeutic target for breast cancer treatment. PMID- 26844698 TI - Constitutive p53 heightens mitochondrial apoptotic priming and favors cell death induction by BH3 mimetic inhibitors of BCL-xL. AB - Proapoptotic molecules directly targeting the BCL-2 family network are promising anticancer therapeutics, but an understanding of the cellular stress signals that render them effective is still elusive. We show here that the tumor suppressor p53, at least in part by transcription independent mechanisms, contributes to cell death induction and full activation of BAX by BH3 mimetic inhibitors of BCL xL. In addition to mildly facilitating the ability of compounds to derepress BAX from BCL-xL, p53 also provides a death signal downstream of anti-apoptotic proteins inhibition. This death signal cooperates with BH3-induced activation of BAX and it is independent from PUMA, as enhanced p53 can substitute for PUMA to promote BAX activation in response to BH3 mimetics. The acute sensitivity of mitochondrial priming to p53 revealed here is likely to be critical for the clinical use of BH3 mimetics. PMID- 26844699 TI - Unfolded protein response-induced dysregulation of calcium homeostasis promotes retinal degeneration in rat models of autosomal dominant retinitis pigmentosa. AB - The molecular mechanism of autosomal dominant retinitis pigmentosa (ADRP) in rats is closely associated with a persistently activated unfolded protein response (UPR). If unchecked, the UPR might trigger apoptosis, leading to photoreceptor death. One of the UPR-activated cellular signaling culminating in apoptotic photoreceptor cell death is linked to an increase in intracellular Ca(2+). Therefore, we validated whether ADRP retinas experience a cytosolic Ca(2+) overload, and whether sustained UPR in the wild-type retina could promote retinal degeneration through Ca(2+)-mediated calpain activation. We performed an ex vivo experiment to measure intracellular Ca(2+) in ADRP retinas as well as to detect the expression levels of proteins that act as Ca(2+) sensors. In separate experiments with the subretinal injection of tunicamycin (UPR inducer) and a mixture of calcium ionophore (A231278) and thapsigargin (SERCA2b inhibitor) we assessed the consequences of a sustained UPR activation and increased intracellular Ca(2+) in the wild-type retina, respectively, by performing scotopic ERG, histological, and western blot analyses. Results of the study revealed that induced UPR in the retina activates calpain-mediated signaling, and increased intracellular Ca(2+) is capable of promoting retinal degeneration. A significant decline in ERG amplitudes at 6 weeks post treatment was associated with photoreceptor cell loss that occurred through calpain-activated CDK5-pJNK Csp3/7 pathway. Similar calpain activation was found in ADRP rat retinas. A twofold increase in intracellular Ca(2+) and up- and downregulations of ER membrane-associated Ca(2+)-regulated IP3R channels and SERCA2b transporters were detected. Therefore, sustained UPR activation in the ADRP rat retinas could promote retinal degeneration through increased intracellular Ca(2+) and calpain mediated apoptosis. PMID- 26844700 TI - MicroRNA-222 regulates muscle alternative splicing through Rbm24 during differentiation of skeletal muscle cells. AB - A number of microRNAs have been shown to regulate skeletal muscle development and differentiation. MicroRNA-222 is downregulated during myogenic differentiation and its overexpression leads to alteration of muscle differentiation process and specialized structures. By using RNA-induced silencing complex (RISC) pulldown followed by RNA sequencing, combined with in silico microRNA target prediction, we have identified two new targets of microRNA-222 involved in the regulation of myogenic differentiation, Ahnak and Rbm24. Specifically, the RNA-binding protein Rbm24 is a major regulator of muscle-specific alternative splicing and its downregulation by microRNA-222 results in defective exon inclusion impairing the production of muscle-specific isoforms of Coro6, Fxr1 and NACA transcripts. Reconstitution of normal levels of Rbm24 in cells overexpressing microRNA-222 rescues muscle-specific splicing. In conclusion, we have identified a new function of microRNA-222 leading to alteration of myogenic differentiation at the level of alternative splicing, and we provide evidence that this effect is mediated by Rbm24 protein. PMID- 26844701 TI - Low levels of Caspase-3 predict favourable response to 5FU-based chemotherapy in advanced colorectal cancer: Caspase-3 inhibition as a therapeutic approach. AB - Colorectal cancer (CRC) is one of the most common cancers in the Western world. 5 Fluorouracil (5FU)-based chemotherapy (CT) remains the mainstay treatment of CRC in the advanced setting, and activates executioner caspases in target cells. Executioner caspases are key proteins involved in cell disassembly during apoptosis. Activation of executioner caspases also has a role in tissue regeneration and repopulation by stimulating signal transduction and cell proliferation in neighbouring, non-apoptotic cells as reported recently. Tissue microarrays (TMAs) consisting of tumour tissue from 93 stage II and III colon cancer patients were analysed by immunohistochemistry. Surprisingly, patients with low levels of active Caspase-3 had an increased disease-free survival time. This was particularly pronounced in patients who received 5FU-based adjuvant CT. In line with this observation, lower serum levels of active Caspase-3 were found in patients with metastasised CRC who revealed stable disease or tumour regression compared with those with disease progression. The role of Caspase-3 in treatment responses was explored further in primary human tumour explant cultures from fresh patient tumour tissue. Exposure of explant cultures to 5FU-based CT increased the percentage of cells positive for active Caspase-3 and Terminal Deoxynucleotidyl Transferase dUTP Nick end Labelling (TUNEL), but also the expression of regeneration and proliferation markers beta-Catenin and Ki-67, as well as cyclooxygenase-2 (COX-2). Of note, selective inhibition of Caspase-3 with Ac-DNLD-CHO, a selective, reversible inhibitor of Caspase-3, significantly reduced the expression of proliferation markers as well as COX-2. Inhibition of COX-2 with aspirin or celecoxib did not affect Caspase-3 levels but also reduced Ki-67 and beta-Catenin levels, suggesting that Caspase-3 acted via COX-2 to stimulate cell proliferation and tissue regeneration. This indicates that low levels of active Caspase-3 may represent a new predictor of CT responsiveness, and inhibition of Caspase-3, or antagonising downstream effectors of Caspase-3 paracrine signalling, such as COX-2 may improve patient outcomes following CT in advanced CRC. PMID- 26844704 TI - Mn concentration-dependent tuning of Mn(2+) d emission of Zn1-xMnxTe nanocrystals grown in a glass system. AB - We studied the effect of Mn concentration on the optical, morphological and magnetic properties of Zn1-xMnxTe NCs grown in a glass matrix produced by the fusion method. The physical properties of these materials were determined by optical absorption (OA), transmission electron microscopy (TEM), atomic/magnetic force microscopy (AFM/MFM) and photoluminescence (PL). An analysis of the OA spectra, based on the crystal field theory (CFT), showed strong evidence that Mn(2+) ions were substitutionally incorporated into the Zn1-xMnxTe NCs until reaching the solubility limit (concentration, x = 0.100). Above this nominal concentration, TEM showed the onset of Mn-related phases, such as MnO and alpha MnO2, in the PZABP glass system. AFM images showed that NC density on the surface of the glass matrix decreased as x-content increased. It is probable that MnO and MnO2 NCs would outnumber Zn1-xMnxTe NCs at higher concentrations - a conclusion that was corroborated by the OA spectra and TEM images. MFM images revealed that samples with Mn(2+) ions responded to magnetization from an MFM probe. This implied that Mn(2+) ions were incorporated within the Zn1-xMnxTe NCs and gave rise to the diluted magnetic semiconductor (DMS) structure. The PL spectra not only confirmed the evidence obtained by OA, CFT, TEM and AFM/MFM, but also showed that Mn(2+) concentration could be used to tune (4)T1((4)G) -> (6)A1((6)S) emission energy. PMID- 26844702 TI - c-Met and CREB1 are involved in miR-433-mediated inhibition of the epithelial mesenchymal transition in bladder cancer by regulating Akt/GSK-3beta/Snail signaling. AB - Emerging evidence has suggested that microRNAs (miRNAs) have an important role in tumor development and progression by regulating diverse cellular pathways. Here we describe the function and regulation network of miR-433 in bladder cancer (BCa). miR-433 is frequently downregulated in BCa tissues compared with adjacent non-cancerous tissues. Epigenetic mechanisms may be involved in the regulation of miR-433 expression. Enforced expression of miR-433 significantly inhibits proliferation, colony formation, migration, and invasion in BCa cells. In addition, miR-433 inhibits the epithelial-mesenchymal transition (EMT) in BCa cells by regulating c-Met/Akt/GSK-3beta/Snail signaling pathway. Both c-Met and CREB1 are downstream target genes of miR-433. CREB1 can also indirectly regulate c-Met/Akt/GSK-3beta/Snail signaling via MITF. Furthermore, CREB1 expression is an independent prognostic factor for overall survival in patients with BCa. Finally, there appears to exist a reciprocal regulation between c-Met and miR-433/miR-409 3p. Taken together, this study reveals that miR-433-c-MET/CREB1-Akt/GSK 3beta/Snail signaling is critical to EMT in BCa. Targeting the pathway described here may open up new prospects to restrict metastatic progression of BCa. PMID- 26844705 TI - The cost of managing severe hypoglycemic episodes in Type 2 diabetic patients. AB - INTRODUCTION: Hypoglycemia is an acute complication of diabetes that increases morbidity, mortality and disease costs. We aim to estimate healthcare resource consumption and costs associated with severe hypoglycemia using the societal perspective. METHODS: A cross-sectional, observational, nationwide, multicenter, hospital-based study was conducted in seven centers of Portuguese mainland with a 1-year enrolment period. Unit costs were extracted from official/public data sources. Patient-level data were used to quantify healthcare resource use related to emergency transportation, emergency-department care and hospitalization. Productivity loss was calculated based on the Human Capital Approach. RESULTS: The study enrolled 238 Type-2 diabetic patients and the proportion of hypoglycemic episodes among all emergency events during the study period was 0.075% (95% CI: 0.067-0.083%). Mean patient age was 76 years and 57.6% were female. At time of the emergency department admission, 55% of patients were using insulin, 31.5% were being treated with secretagogues, 6.7% were on a combination of both, and 6.7% were on other oral antihyperglycemic agents. Estimated mean costs in the emergency department were: emergency transportation ?33, medication ?4, laboratory workup ?56, other exams ?72, physician and nurse time ?30 and ?13, respectively. Mean hospitalization cost was ?1271. Indirect cost averaged ?15. Overall cost per hypoglycemic episode averaged ?1493 (standard deviation: ?2962; range: ?34-26,818). Patients treated with secretagogues had the highest rates of hospitalizations and mean costs. CONCLUSION: We conclude that severe hypoglycemic events represent a substantial cost for society and in particular for the hospitals of the National Health Service. PMID- 26844706 TI - A portable SERS method for the determination of uric acid using a paper-based substrate and multivariate curve resolution. AB - This paper presents a portable quantitative method for the on-site determination of uric acid in urine using surface-enhanced Raman spectroscopy (SERS) and gold nanoparticle-coated paper as a substrate. A procedure was developed for the rapid preparation of cost-effective SERS substrates that enabled the adequate control of a homogeneous active area and the use of small quantities of gold nanoparticles per substrate. The standard addition method and multivariate curve resolution-alternating least squares (MCR-ALS) were applied to compensate for the matrix effect and to address overlapping bands between uric acid and interference SERS spectra. The proposed methodology demonstrated better performance than conventional univariate methods (in terms of linearity, accuracy and precision), a wide linear range (0-3.5 mmol L(-1)) and an adequate limit of detection (0.11 mmol L(-1)). For the first time, a portable SERS method coupled with chemometrics was developed for the routine analysis of uric acid at clinically relevant concentrations with minimal sample preparation and easy extension for the on-site determination of other biomarkers in complex sample matrices. PMID- 26844707 TI - Prevalence and Correlates of Disruptive Mood Dysregulation Disorder Among Adolescents with Bipolar Disorder. AB - OBJECTIVE: The purpose of this study was to examine the prevalence and correlates of disruptive mood dysregulation disorder phenotype (DMDDP) in a clinical population of adolescents with bipolar disorder (BD). METHODS: DMDD criteria were modified and applied to a sample of 116 adolescents with BD-I (n = 30), BD-II (n = 46) or BD-not otherwise specified (NOS) (n = 40) from a tertiary teaching hospital. Diagnoses were determined via the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children, Present and Lifetime version (KSADS-PL). Diagnostic and Statistical Manual of Mental Disorders (DSM-5) DMDD Criteria A-G were derived from the KSADS oppositional defiant disorder (ODD) screening interview and supplement, as well as narrative summaries. Chi-square analyses or t tests (p < 0.05) were conducted as appropriate, followed by logistic regression. P values were adjusted using the false discovery rate (FDR) approach. RESULTS: DMDDP criteria could not be determined for 8 adolescents because of missing data from the ODD supplement. Twenty-five percent of the remainder (27/108) met criteria for DMDDP. DMDDP was not associated with BD subtype or with family history of BD. In univariate analyses, after controlling for age, sex, and race, DMDDP was associated with lower functioning, increased family conflict, assault history, and attention deficit and/or hyperactivity disorder (ADHD) (FDR adjusted p values: <0.0001, < 0.0001, 0.007, and 0.007, respectively). Lifetime substance use disorder and medication use approached significance (adjusted p = 0.05). In logistic regression, DMDDP was independently associated with greater parent-reported family conflict (odds ratio [OR] 1.17; confidence interval [CI- 1.06-1.30; p = 0.001) and greater functional impairment (OR 0.89; CI 0.82-0.97; p = 0.006). DMDDP was also associated with a threefold increase in ADHD, although ADHD was only marginally significant (OR 3.3; CI 0.98 10.94; p = 0.05). CONCLUSIONS: Despite the positioning of DMDD as phenotypically and biologically distinct from BD, these phenotypes commonly overlap in clinical settings. This overlap is not explained by BD-NOS or by nonfamilial BD. The association of ADHD with DMDDP in this sample draws into question whether arousal symptoms should have been retained as originally elaborated in the severe mood dysregulation phenotype. Strategies to mitigate the excessive functional impairment of this comorbidity are warranted. PMID- 26844708 TI - Risk-reducing surgery on the uterine adnexa: timing and type of surgical treatment, and pathology report. AB - Inherited mutations in BRCA1 and BRCA2 increase significantly the risk of developing breast and ovarian cancers, and they have been associated with increased risks of developing other types of cancer. Although screening programs have been implemented in order to detect cancers at the early stage, they resulted ineffective. To date, risk-reducing bilateral salpingo-oophorectomy represents the only procedure allowing reducing the incidence of ovarian cancer and increasing survival among BRCA1 and -2 mutation carriers. In the present review we will discuss the advantages and disadvantages related to the execution of prophylactic surgery, thus underlying possible beneficial and detrimental effects of this kind of surgery in premenopausal women. Additionally, we will investigate further therapeutic strategies aimed to reduce the risk of developing ovarian cancer, without affected patients' hormonal status. PMID- 26844709 TI - Breast Ultrasonography: Findings in Pediatric Patients. AB - Purpose To analyze referral indications, imaging findings and diagnoses in breast sonography in a division of pediatric radiology. Materials and Methods Breast ultrasound examinations of 270 patients were analyzed for referral reasons, imaging findings and final diagnoses (152 females, 118 males). The mean age of the patients was 8.8 years (range, 6 days-18 years). Each breast was examined systematically in two orthogonal probe orientations. Pathological findings were documented on two orthogonal imaging planes. Color Doppler ultrasonography was used additionally. Images and clinical data were reviewed in all cases. Results The most frequent referral reasons in female patients were breast enlargement (104 patients), palpable mass (24 patients) and mastodynia (23 patients). The most frequent diagnoses were normal gland tissue (101 patients), cysts (9 patients), augmented adipose tissue (7 patients) and hemangiomas (7 patients). The most frequent referral reasons in male patients were breast enlargement (106 patients), palpable mass (13 patients) and mastodynia (9 patients). The most frequent diagnoses were gland tissue (79 patients), augmented adipose tissue (24 patients) and cysts (10 patients). Only 2 malignant masses were diagnosed: A Burkitt lymphoma and a relapsed ALL. Conclusion Fear of breast cancer and permanent damage to the breast leads to low-threshold medical consultations and referrals. Sensitive handling is required especially in adolescent patients. Most disorders arise due to the variability of breast development. Ultrasound serves as a means to exclude significant diseases of the breast. PMID- 26844710 TI - Color Tissue Doppler to Analyze Fetal Cardiac Time Intervals: Normal Values and Influence of Sample Gate Size. AB - PURPOSE: To assess the time intervals of the cardiac cycle in healthy fetuses in the second and third trimester using color tissue Doppler imaging (cTDI) and to evaluate the influence of different sizes of sample gates on time interval values. MATERIALS AND METHODS: Time intervals were measured from the cTDI derived Doppler waveform using a small and large region of interest (ROI) in healthy fetuses. RESULTS: 40 fetuses were included. The median gestational age at examination was 26 + 1 (range: 20 + 5 - 34 + 5) weeks. The median frame rate was 116/s (100 - 161/s) and the median heart rate 143 (range: 125 - 158) beats per minute (bpm). Using small and large ROIs, the second trimester right ventricular (RV) mean isovolumetric contraction times (ICTs) were 39.8 and 41.4 ms (p = 0.17), the mean ejection times (ETs) were 170.2 and 164.6 ms (p < 0.001), the mean isovolumetric relaxation times (IRTs) were 52.8 and 55.3 ms (p = 0.08), respectively. The left ventricular (LV) mean ICTs were 36.2 and 39.4 ms (p = 0.05), the mean ETs were 167.4 and 164.5 ms (p = 0.013), the mean IRTs were 53.9 and 57.1 ms (p = 0.05), respectively. The third trimester RV mean ICTs were 50.7 and 50.4 ms (p = 0.75), the mean ETs were 172.3 and 181.4 ms (p = 0.49), the mean IRTs were 50.2 and 54.6 ms (p = 0.03); the LV mean ICTs were 45.1 and 46.2 ms (p = 0.35), the mean ETs were 175.2 vs. 172.9 ms (p = 0.29), the mean IRTs were 47.1 and 50.0 ms (p = 0.01), respectively. CONCLUSION: Isovolumetric time intervals can be analyzed precisely and relatively independent of ROI size. In the near future, automatic time interval measurement using ultrasound systems will be feasible and the analysis of fetal myocardial function can become part of the clinical routine. PMID- 26844711 TI - Investigation of thermal degradation with extrusion-based dispensing modules for 3D bioprinting technology. AB - Recently, numerous three-dimensional (3D) bioprinting systems have been introduced for the artificial regeneration of tissues. Among them, the extrusion based dispensing module is the most widely used because of the processability it gives various biomaterials. The module uses high forces and temperature to dispense materials through a micro-nozzle. Generally, the harsh conditions induce thermal degradation of the material in the dispensing procedure. The thermal degradation affects the properties of the materials, and the change of the properties should be carefully controlled, because it severely affects the regeneration of tissues. Therefore, in this research, the relationship between the dispensing module and the thermal degradation of material was investigated. Extrusion-based dispensing modules can be divided into the syringe type (ST) and filament type (FT) based on working principles. We prepared a poly lactic-co glycolic acid (PLGA) scaffold with the two methods at various time points. Then, the characteristics of the printed scaffolds were assessed by measuring molecular weight (M w), glass transition temperature (T g), in vitro degradation, compressive modulus, and cytocompatibility. The results showed that the PLGA scaffold with the FT dispensing module maintained its properties regardless of printing time points. In contrast, severe thermal degradation was observed in the scaffold group prepared by the ST dispensing module. Consequentially, it was obvious that the FT dispensing module was more suitable for producing scaffolds without severe thermal degradation. PMID- 26844712 TI - Mindfulness, Multitasking, and You. AB - The ability to multitask has been typically worn like a badge of honor for all case managers. Mindfulness, on the contrary, is the new kid on the block and is proving to increase resilience and decrease stress. Research shows that multitasking lowers IQ, shrinks the gray matter, and lowers productivity by 40%. Conversely, mindfulness increases gray matter and improves regions involved with learning and memory processes, modulation of emotional control, and the process of awareness. The research leaves more questions than answers but may be a key to engaged, focused, and less-stressed staff. PMID- 26844713 TI - Employer Satisfaction With an Injured Employee's Health Care: How Does It Affect the Selection of an Occupational Health Care Provider? AB - PURPOSE/OBJECTIVES: The purpose of this article is to explore the most important factors that an employer utilizes in selecting an occupational health care provider for their employees injured on the job. PRIMARY PRACTICE SETTING(S): The primary practice setting is the attending physician's office who is an occupational health care provider. FINDINGS/CONCLUSIONS: The responding employers deemed "work restrictions given after each office visit" as their most important factor in selecting an occupational health care provider, with a score of 43. This was followed in order in the "very important" category by communication, appointment availability, employee return to work within nationally recognized guidelines, tied were medical provider professionalism and courtesy with diagnostics ordered timely, next was staff professionalism and courtesy, and tied with 20 responses in the "very important" category were wait time and accurate billing by the provider.The selection of an occupational health care provider in the realm of workers' compensation plays a monumental role in the life of a claim for the employer. Safe and timely return to work is in the best interest of the employer and their injured employee. For the employer, it can represent hard dollars saved in indemnity payments and insurance premiums when the employee can return to some form of work. For the injured employee, it can have a positive impact on their attitude of going back to work as they will feel they are a valued asset to their employer. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: The case managers, who are the "eyes and ears" for the employer in the field of workers' compensation, have a valuable role in a successful outcome of dollars saved and appropriate care rendered for the employees' on the job injury. The employers in the study were looking for case managers who could ensure their employees received quality care but that this care is cost-effective. The case manager can be instrumental in assisting the employer in developing and monitoring a "stay-at-work" program, thereby reducing the financial exposure for the employer. PMID- 26844714 TI - Avoidable Technical and Clinical Denial Write-Off Management in Hospitals, Physician Offices, and Clinics. AB - PURPOSE/OBJECTIVES: This article reviews the various types of technical and clinical denials that are usually "written off" and proposes strategies to prevent this loss. For purposes of this writing, avoidable technical and clinical denial write-offs are defined as revenue lost from "first-pass" denials rejections. For example, a procedure that requires an authorization is performed without having had an authorization obtained. After appeals and attempts to recoup the revenue, often unsuccessful, the organization ultimately "writes off" the revenue as not collectable. The question to ask is: Are these claims really not collectable or can actionable steps be taken to conserve these dollars and improve the bottom line? PRIMARY PRACTICE SETTING: Acute care hospitals, physician offices, and clinics. FINDINGS AND CONCLUSIONS: In today's environment, the need to manage costs is ubiquitous. Cost management is on the priority list of all savvy health care executives, even if margins are healthy, revenue is under pressure, and the magnitude of cost reduction needed is greater than what past efforts have achieved. As hospitals and physician clinics prioritize areas for improvement, reduction in lost revenue-especially avoidable lost revenue should be at the top of the list. Attentively managing claim denial write-offs will significantly reduce lost revenue. IMPLICATIONS FOR CASE MANAGEMENT: There is significant interface between case management and the revenue cycle. Developing core competencies for reducing clinical and technical denials should be a critical imperative in overall cost management strategy. Case managers are well placed to prevent these unnecessary losses through accurate status determination and clinical documentation review. These clinical professionals can also provide insight into work flow and other processes inherent in the preauthorization process. PMID- 26844715 TI - Case Management Promotion of Social Media for the Elderly Who Live Alone. AB - PURPOSE: Professional case managers advocate patient access to necessary and appropriate services, while educating the patient and family and/or caregiver about resource availability within practice settings. The purpose of this article is to explain the role case managers can have to promote the use of social media by the elderly, as a means to decrease their loneliness and isolation. PRIMARY PRACTICE SETTINGS: The promotion of the use of social media will take place in the community setting, involving willing and competent elderly patients who live alone. It is framed as one strategy to help combat loneliness. The primary target audiences for this initiative are case managers who work in the community, as they are the ones who have contact with this population. However, hospital case managers could also benefit, as they need to be aware of ways to help discharged elderly patients feel more connected to their community; the use of social media is one way to achieve this outcome. FINDINGS: The elderly population experience changes brought on by their longer life. One of those changes or undesirable effects is an increase in social isolation and experiencing loneliness. There are many factors that contribute to loneliness and social isolation in the elderly such as a change in financial situations, death, divorce, or migration. Utilizing the capabilities of the internet, coupled with the use of social media (e.g., Facebook), can facilitate opening up a virtual world where the elderly can communicate with family and friends, make new friends, or occupy their time with the many interactive games that are available online. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Case managers should increase their awareness to identify patients who are socially isolated; the outcome is to decrease the risk of developing a major depressive disorder. Community case managers might at times be the only professional health care givers who are visiting patients in their home; therefore, they should also be aware of the signs and symptoms of depression so they can encourage patients to get the necessary help needed as soon as possible. This article identifies key case management strategies to promote the use of social media by isolated elderly clients that include assessment of their learning needs and capabilities, devising a plan of action, implementation of technology, and evaluation and follow-up of the implementation. PMID- 26844716 TI - Medical Ethics Made Easy. AB - PURPOSE/OBJECTIVES: Case managers (CMs) today are involved in many different care scenarios. They collaborate with many professionals in the multidisciplinary care team. CMs work to facilitate improved patient outcomes and help patients, family members, and providers establish and work toward similar goals. Often these involve end-of-life and critical care, which can call ethics consultations or utilization of other resources to help facilitate communication toward these goals. The objective of this article was to help increase CMs comfort level with starting to apply the 4 basic ethical principles to practice in basic concept. PRIMARY PRACTICE SETTING(S): Inpatient acute care as well as outpatient settings, such as physician offices, and home health care settings. FINDINGS/CONCLUSIONS: Knowledge and a comfort level in applying the 4 ethical principles can help establish the CM role in facilitating communication among care providers, as they work toward a common goal in the treatment plan. Understanding the principles and applying them in basic concept can help CMs participate in conflict resolution or appropriate referrals to ethics committees. IMPLICATIONS FOR CASE MANAGEMENT PRACTICE: Complex medical situations and care issues can lead to conflicts. Knowledge of basic ethical principles and core concepts may be a useful tool for CMs as they collaborate and communicate with patients, family members, and health care providers. Facilitating communication about the treatment plan, and acting as patient advocate, can optimize outcomes and potentially reduce length of stay. PMID- 26844717 TI - Why Care Coordination Matters! PMID- 26844718 TI - The Business of Case Management. PMID- 26844719 TI - Educating Case Managers: Will On-the-Job Training Be Enough? PMID- 26844720 TI - Health IT Collaboration and Coordination. PMID- 26844723 TI - Phase III Study on Efficacy and Safety of Triple Combination (Exenatide/Metformin/Biphasic Insulin Aspart) Therapy for Type 2 Diabetes Mellitus. AB - Exenatide, metformin (MET), and biphasic insulin aspart 30 (BIA30) have been widely used in the treatment of patients with type 2 diabetes mellitus (T2DM); however, each of these medications has significant adverse effects, which limit their utilization. This study aimed to evaluate the efficacy and safety of triple combination (exenatide/metformin/biphasic insulin aspart) therapy for T2DM. Two hundred patients with poorly controlled T2DM were randomly divided into the low dose (0.5 MUg exenatide, 0.05 U.kg.d BIA30, and 0.01 g MET twice daily) and normal-dose (2 MUg exenatide, 0.2 U.kg.d BIA30, and 0.05 g MET twice daily) groups for 48 weeks of treatment. Of note, 82 and 90 individuals from the low dose and normal-dose groups, respectively, completed the study. The levels of adiponectin, C-reactive protein, tumor necrosis factor-alpha, and resistin were measured. The normal-dose treatment was more effective at lowering hemoglobin A1c levels than the low-dose therapy (HbA1c changes of -2.5 +/- 0.19% and -0.8 +/- 0.07%, respectively) after 48 weeks. The maximum weight decrease was 0.9 kg in the low-dose group and 4.0 kg in the normal-dose group. The triple combination therapy increased the levels of insulin sensitivity and adiponectin and reduced the levels of C-reactive protein, resistin, and tumor necrosis factor-alpha. No significant difference in the adverse effects was found between the low-dose and normal-dose groups (P > 0.05). In conclusion, the investigated triple combination therapy for T2MD is therefore an effective and safe therapeutic strategy. PMID- 26844727 TI - An Anthology of Epileptology. PMID- 26844728 TI - Diagnosis of Epilepsy and Related Episodic Disorders. AB - PURPOSE OF REVIEW: This review identifies the diverse and variable clinical presentations associated with epilepsy that may create challenges in diagnosis and treatment. RECENT FINDINGS: Epilepsy has recently been redefined as a disease characterized by one or more seizures with a relatively high recurrence risk (ie, 60% or greater likelihood). The implication of this definition for therapy is that antiepileptic drug therapy may be initiated following a first seizure in certain situations.EEG remains the most commonly used study in the evaluation of people with epilepsy. Routine EEG may assist in diagnosis, classification of seizure type(s), identification of treatment, and monitoring the efficacy of therapy. Video-EEG monitoring permits seizure classification, assessment of psychogenic nonepileptic seizures, and evaluation of candidacy for epilepsy surgery. MRI is pivotal in elucidating the etiology of the seizure disorder and in suggesting the localization of seizure onset. SUMMARY: This article reviews the new International League Against Epilepsy practical clinical definition for epilepsy and the differential diagnosis of other physiologic paroxysmal spells, including syncope, parasomnias, transient ischemic attacks, and migraine, as well as psychogenic nonepileptic seizures. The initial investigational approaches to new-onset epilepsy are considered, including neuroimaging and neurophysiologic investigations with interictal and ictal video-EEG. Neurologists should maintain a high index of suspicion for epilepsy when children or adults present with a single paroxysmal spell or recurrent episodic events. PMID- 26844729 TI - Management of a First Seizure. AB - PURPOSE OF REVIEW: Assessment of the patient with a first seizure is a common and important neurologic issue. Less than 50% of patients who have a first unprovoked seizure have a second seizure; thus, the evaluation should focus on determining the patient's risk of seizure recurrence. RECENT FINDINGS: A number of population studies, including some classic reports, have identified the relative risk factors for subsequent seizure recurrence. The 2014 update of the International League Against Epilepsy definition of epilepsy incorporates these findings, and in 2015, the American Academy of Neurology published a guideline that analyzed the available data. SUMMARY: Provoked or acute symptomatic seizures do not confer increased risk for subsequent unprovoked seizure recurrence. Multiple seizures in a given 24-hour period do not increase the risk of seizure recurrence. Remote symptomatic seizures, an epileptiform EEG, a significant brain imaging abnormality, and nocturnal seizures are risk factors for seizure recurrence. Antiepileptic drug therapy delays the time to second seizure but may not influence long-term remission. PMID- 26844730 TI - Febrile Seizures. AB - PURPOSE OF REVIEW: This article provides an update on the current understanding and management of febrile seizures. Febrile seizures are one of the most common age-related epileptic convulsions that lead to outpatient consultations, emergency department visits, and hospital or intensive care admissions. RECENT FINDINGS: The Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT) study, an ongoing multicenter prospective longitudinal study, is providing valuable insights into the subset of patients who develop febrile status epilepticus, the most life-threatening type of febrile seizures with potential long-term consequences. Mutations in voltage-gated ion channels and neurotransmitter receptor genes have been shown to result in familial occurrence of febrile seizures and epilepsy. Acute abortive treatment of febrile seizures using a commercially available rectal delivery kit has gained widespread use by nonmedical caregivers as a first-line treatment at home. SUMMARY: Most febrile seizures are self-limiting episodes with low risk of injury, death, and long-term neurologic consequences. Most fevers and infections that cause febrile seizures are relatively benign and do not require extensive testing or procedures. Long term management requires thorough assessment and risk stratification to devise a customized plan for each child, paying attention to the caregiver situation at home and day care. Most important treatment efforts are directed at caregiver education and, when appropriate, on effective use of abortive seizure treatment at home. PMID- 26844731 TI - Infantile, Childhood, and Adolescent Epilepsies. AB - PURPOSE OF REVIEW: Infantile, childhood, and adolescent epilepsies comprise a diverse group of entities. Careful characterization of epilepsy into a specific electroclinical syndrome or etiology assists greatly in understanding both the natural history of the seizure disorder (pharmacoresistant versus pharmacoresponsive and self-limited versus lifelong) and the best therapeutic options for the child. RECENT FINDINGS: Tremendous growth has been seen in the understanding of both genetic factors predisposing to epilepsy and neuroimaging techniques. Additionally, a number of studies have focused on the efficacy of certain therapies in specific syndromes or etiologies. SUMMARY: This article reviews both common epilepsy syndromes (including benign focal epilepsy of childhood, absence epilepsy, and juvenile myoclonic epilepsy) and the rarer syndromes with associated management implications (eg, Dravet syndrome, progressive myoclonic epilepsy, and mitochondrial disorders) and addresses genetic and metabolic investigations. PMID- 26844732 TI - Adult Focal Epilepsies. AB - PURPOSE OF REVIEW: Focal epilepsy is the most common type of epilepsy in adulthood. This article discusses the seizure symptomatology, EEG findings, and imaging findings of the various forms of focal epilepsy. The majority of the article focuses on temporal and frontal lobe epilepsy as these represent the majority of focal epilepsies. RECENT FINDINGS: While significant overlap exists in the clinical symptomatology of the focal epilepsies, detailed seizure descriptions can often provide useful clinical evidence to help establish an accurate diagnosis. EEG and MRI continue to serve as the main diagnostic tools for the diagnosis of focal epilepsy. SUMMARY: The various forms of focal epilepsy generate seizure presentations that are dependent on the anatomic structures that are involved in the seizure. By understanding the symptoms typically generated in each region of the brain, a better understanding of the possible seizure localizations can be made. Most forms of epilepsy have clear changes on EEG that permit accurate localization, but several pitfalls exist, which are discussed in this article. Imaging has revolutionized our ability to accurately identify lesions associated with epilepsy and increased our ability to localize seizures in the brain. PMID- 26844733 TI - Diagnosis and Treatment of Nonepileptic Seizures. AB - PURPOSE OF REVIEW: This article details the evaluation process involved in the diagnosis of psychogenic nonepileptic seizures (PNES). The psychological underpinnings, prognostic factors, and recent treatment advances of PNES are also reviewed. RECENT FINDINGS: The diagnosis of PNES is determined based on concordance of the composite evidence available, including historical and physical examination findings, seizure symptoms and signs, and ictal/interictal EEG. No single clinical data point is definitively diagnostic of PNES. The diagnosis of PNES can be challenging at times, such as when seizure documentation on video-EEG cannot be readily obtained. Yet, delayed diagnosis of PNES portends poor outcome. A multicomponent approach to the diagnosis of PNES, with use of an aggregate of available evidence, may facilitate diagnosis and then care of patients with PNES. Emerging evidence supports the effectiveness of cognitive behavioral-based therapy in the treatment of these patients. SUMMARY: The diagnosis of PNES can be made reliably, and evidence-based treatment now exists. Continued efforts remain necessary to enhance prompt recognition and interdisciplinary management for patients with PNES. PMID- 26844734 TI - Antiepileptic Drugs. AB - PURPOSE OF REVIEW: Treatment of epilepsy starts with antiepileptic drug (AED) monotherapy. Knowledge of the spectrum of efficacy, clinical pharmacology, and modes of use for individual AEDs is essential for optimal treatment for epilepsy. This article addresses AEDs individually, focusing on key pharmacokinetic characteristics, indications, and modes of use. RECENT FINDINGS: Older-generation AEDs are effective but have tolerability and pharmacokinetic disadvantages. Several newer-generation AEDs have undergone comparative trials demonstrating efficacy equal to and tolerability at least equal to or better than older AEDs as first-line therapy. The list includes lamotrigine, oxcarbazepine, levetiracetam, topiramate, and, more recently, zonisamide. Pregabalin was found to be less effective than lamotrigine. Lacosamide, pregabalin, and eslicarbazepine have undergone successful trials of conversion to monotherapy. Other newer-generation AEDs with a variety of mechanisms of action are suitable for adjunctive therapy. Rational AED combinations should avoid AEDs with unfavorable pharmacokinetic interactions or pharmacodynamic interactions related to mechanism of action. SUMMARY: Knowledge of AED pharmacokinetics, efficacy, and tolerability profiles facilitates the choice of appropriate AED therapy for patients with epilepsy. PMID- 26844735 TI - Management of Drug-Resistant Epilepsy. AB - PURPOSE OF REVIEW: This review discusses the definition, evaluation, and management of patients with drug-resistant epilepsy. RECENT FINDINGS: Drug resistant epilepsy is defined as a failure of two or more appropriately selected and adequately tried anticonvulsant medications to achieve seizure freedom for a sustained period of time in either monotherapy or polytherapy. Once this definition has been met, the likelihood that further medication trials will lead to seizure freedom is in the range of 5% to 10%. Reasons for pseudoresistance to anticonvulsant therapy include wrong diagnosis, wrong drug, wrong dose, or poor compliance. Patients with epilepsy who are drug resistant should be referred to an epilepsy center for a surgical evaluation or more specialized care. The odds of being seizure free following epilepsy surgery versus continued medications are around 4 to 3. Currently, surgical referrals occur late in the disease. SUMMARY: Determination of drug-resistant epilepsy and referral to an epilepsy surgical center can be expedited to avoid exposing patients to continued seizures and the resultant morbidity. PMID- 26844736 TI - Epilepsy Emergencies. AB - PURPOSE OF REVIEW: Epilepsy emergencies include acute repetitive seizures and status epilepticus. Their prognosis depends on the etiology of the seizures and the time spent in status epilepticus. This review discusses the current perspective on the diagnosis and treatment of status epilepticus and acute repetitive seizures in the intensive care unit. RECENT FINDINGS: Current data on the treatment of status epilepticus emphasize early treatment over the choice of antiepileptic drug. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) data support the efficacy of prehospital treatment using faster routes of benzodiazepine administration. As additional antiepileptic drugs have become available in an IV formulation, their use in status epilepticus has increased, with little data to guide their administration. Recent publications have also stressed the changing epidemiology of status epilepticus in the United States, with a rise in incidence without much change in overall mortality. This rise is likely related to improved diagnostic capabilities with better availability and usage of continuous EEG in the intensive care unit and to the aging of the patient population. SUMMARY: Acute repetitive seizures and status epilepticus are neurologic emergencies that are being increasingly diagnosed and treated in the modern era. Rapid treatment may influence patient prognosis, future cognitive outcomes, and the long-term potential for developing epilepsy. However, little is known about the mechanisms that perpetuate seizure activity, and our ability to intervene and prevent this condition remains limited. Preventing complications during the treatment of status epilepticus plays a large role in prognosis and the chance of treatment success. PMID- 26844737 TI - Management of Epilepsy Comorbidities. AB - PURPOSE OF REVIEW: Many comorbid conditions occur among people with epilepsy. These comorbid conditions can be divided into physical, psychiatric, and cognitive groups. This article examines the common comorbid conditions associated with epilepsy and identifies management strategies to mitigate these health concerns. RECENT FINDINGS: Sudden unexpected death in epilepsy (SUDEP) is an important and common cause of epilepsy-related mortality, with the most important identified predictor being recurrent seizures. Psychiatric and cognitive comorbidities of epilepsy are also particularly common. Individuals with epilepsy need to be screened and treated for psychiatric comorbidities. SUMMARY: This article explains common comorbid conditions such as depression, anxiety, and memory difficulties; outlines treatment approaches; and discusses functional restrictions such as driving. SUDEP and the risk factors that contribute to it are also discussed. PMID- 26844738 TI - Managing Epilepsy in Women. AB - PURPOSE OF REVIEW: Caring for a woman with epilepsy requires familiarity with the implications of antiepileptic drugs (AEDs) for pregnancy and contraception as well as an understanding of the effects of female hormones on epilepsy. RECENT FINDINGS: AED pregnancy registries and prospective studies of cognitive development continue to confirm that valproate poses a significantly increased risk of structural and cognitive teratogenesis. In contrast, data thus far suggest that lamotrigine and levetiracetam are associated with a relatively low risk for both anatomic and developmental adverse effects, although further studies are needed for these and other AEDs. The intrauterine device is a good contraceptive option for many women with epilepsy as it is highly effective and not subject to the drug-drug interactions seen between hormonal contraception and many AEDs. Hormonal-sensitive seizures are common among women with epilepsy; however, highly effective treatments for refractory catamenial seizures are limited. SUMMARY: Women with epilepsy should be counseled early and regularly about reproductive health as it relates to epilepsy. AED selection for women of childbearing age should take future pregnancies and contraceptive needs into consideration. PMID- 26844739 TI - Autoimmune Epilepsy. AB - PURPOSE OF REVIEW: This review presents recent developments in the clinical features, immunologic basis, and treatment options for autoimmune encephalitis, seizures, and epilepsy. RECENT FINDINGS: In addition to the expansion of our knowledge on classic paraneoplastic limbic encephalitis with onconeural antibodies, recent years have witnessed the development of the category of encephalitis associated with antibodies directed toward neuronal surface antigens. Antibodies against the voltage-gated potassium channel are, in fact, directed toward an array of targets within a large molecular complex. The most common target, leucine-rich, glioma inactivated 1 (LGI1), is associated with a syndrome of limbic encephalitis, sometimes preceded by disease-specific faciobrachial dystonic seizures, which could allow early diagnosis and treatment. Encephalitis with N-methyl-D-aspartate (NMDA) receptor antibodies, only discovered a few years ago, has emerged as the leading syndrome of this new category. Its clinical features and EEG signature are well defined, which should allow prompt recognition and treatment. The list of antibodies is still growing as new antibodies are identified that recognize other synaptic proteins, such as the gamma-aminobutyric acid (GABA), alpha-amino-3-hydroxy-5-methylisoxazole-4 propionic acid (AMPA), and glycine receptors. The role of glutamic acid decarboxylase 65 (GAD65) antibodies is still a controversy, as is the cause of Rasmussen encephalitis and syndromes of cryptogenic refractory status epilepticus and the mechanisms of seizures in systemic autoimmune diseases. A link between autoimmunity and epilepsy has been substantiated by large epidemiologic studies, but the nature of the causality requires more research. SUMMARY: Autoimmune encephalitis is an important cause of seizures to recognize as it entails a specific therapeutic approach. Paraneoplastic limbic encephalitis and NMDA receptor and LGI1 encephalitis are well-characterized immunoclinical associations. Other syndromes and antibodies are being actively identified and described. A concept of autoimmune epilepsy is emerging and, if confirmed, is likely to alter the therapeutic approach and improve the outcome of some patients with pharmacoresistant epilepsy. PMID- 26844740 TI - Special Issues in Epilepsy: The Elderly, the Immunocompromised, and Bone Health. AB - PURPOSE OF REVIEW: This article discusses targeted special issues in epilepsy, including epilepsy in the elderly and immuncompromised populations and bone health in epilepsy. Although this is a broad and diverse set of topics, common themes can be identified by focusing on elderly patients and patients who are immunocompromised that provide a valuable framework for other groups. RECENT FINDINGS: An increasing incidence of epilepsy has been reported in patients 65 years of age and older. As people age, physiologic changes can alter antiepileptic drug metabolism, which can significantly impact dosing requirements and tolerability. Side effects of antiepileptic drugs may pose a significant challenge given the relatively high frequency of comorbid illnesses. When evaluating and treating immunocompromised patients, a broad range of potential etiologies for new-onset or worsening seizures must be considered. When choosing an antiepileptic drug, drug-drug interactions, the potential for increased side effects, and the overall impact of treatments on the underlying illness must be considered. The most recent findings and recommendations pertaining to bone health assessment and maintenance in various populations with epilepsy are summarized. SUMMARY: Treating epilepsy and seizures in special populations requires taking a broad view of patients' overall health status, including potentially complex treatment regimens and a unique predisposition to adverse events. PMID- 26844741 TI - Ethical Considerations in Balancing Parental Autonomy With Protecting a Child With Epilepsy From Harm. AB - Neurologists are expected to accommodate parental decisions in the medical care for their child, unless the parental decision places the child at an unnecessary risk of serious harm. Sometimes, respect for parental autonomy is in conflict with the physician's professional obligation to protect the patient from harm and to optimize treatment for a particular disease or condition. This case illustrates an ethical dilemma created when the neurologist and parent disagree about the most appropriate medical treatment for a child with epilepsy. Viewing the disagreement within an ethical framework, however, provides the parties to the disagreement with an opportunity to understand the beliefs and motivations of everyone involved and creates the potential for an outcome based upon the child's best interest. PMID- 26844742 TI - Cultural Barriers to Medication Adherence in Epilepsy. AB - Antiepileptic drugs can prevent seizures in most patients; however, nonadherence is frequently reported. Nonadherence is associated with a higher incidence of emergency department visits, increased hospital admissions, and an increased risk of mortality. Misconceptions about epilepsy, level of education, and language barriers are contributors to nonadherence. Misconceptions about epilepsy and antiepileptic drugs are prevalent among economically disadvantaged predominantly minority persons with epilepsy. Educational interventions may improve adherence. PMID- 26844743 TI - Diagnostic Coding for Epilepsy. AB - Accurate coding is an important function of neurologic practice. This contribution to Continuum is part of an ongoing series that presents helpful coding information along with examples related to the issue topic. Tips for diagnosis coding, Evaluation and Management coding, procedure coding, or a combination are presented, depending on which is most applicable to the subject area of the issue. PMID- 26844744 TI - Appendix A: Summary of Evidence-Based Guideline for Clinicians: Management of an Unprovoked First Seizure in Adults. PMID- 26844745 TI - Appendix B: AAN Summary of Evidence-Based Guideline for Clinicians: Management Issues for Women With Epilepsy--Focus on Pregnancy: Obstetrical Complications and Change in Seizure Frequency. PMID- 26844746 TI - Appendix C: AAN Summary of Evidence-Based Guideline for Clinicians: Management Issues for Women With Epilepsy--Focus on Pregnancy: Vitamin K, Folic Acid, Blood Levels, and Breastfeeding. PMID- 26844747 TI - Appendix D. Summary of Evidence-based Guideline for CLINICIANS: ANTIEPILEPTIC DRUG SELECTION FOR PEOPLE WITH HIV/AIDS. PMID- 26844750 TI - Patient Management Problem. PMID- 26844753 TI - Worldwide trends in incidence in occupational allergy and asthma. AB - PURPOSE OF REVIEW: Recent improvements in the methods for analyzing trends in occupational health surveillance and the prospect of future improvements in the collecting and sharing of electronic data alongside increasing availability of linked datasets make this a good time to review the existing literature on trends in occupational allergy and asthma (OAA). RECENT FINDINGS: There is a notable lack of reports of recent trends in OAA in the academic literature and much of the published work comes from European countries. The incidence of OAA appears to be declining based on physician-reporting or recognized compensation claims for the countries with published data. However, we need to be cautious in interpreting this as a decline in the 'true' incidence of OAA. Few of the studies adjusted appropriately for changes in the population at risk and one of the most robust study designs showed no change in the incidence of allergic contact dermatitis in contrast to the other studies. SUMMARY: Many existing datasets have the potential to be used to examine trends, and studies from Canada show the potential of using linked databases for surveillance. We hope that this review will encourage improvements in the analysis, and more dissemination, of trends. PMID- 26844754 TI - Assembly mechanism of Trypanosoma brucei BILBO1 at the flagellar pocket collar. AB - The flagellar pocket is a bulb-like invagination of the plasma membrane that encloses the base of the single flagellum in trypanosomes. It is the site of all endo- and exocytic activity in the parasite and has thus been proposed to be a therapeutic target. At the neck of the flagellar pocket is an electron-dense cytoskeletal structure named the flagellar pocket collar. The protein BILBO1 was the first characterized and remains the only known component of the flagellar pocket collar, with essential functions in the biogenesis of both the flagellar pocket and flagellar pocket collar. We recently reported that the filamentous assembly of Trypanosoma brucei BILBO1 (TbBILBO1) is mediated by its central coiled coil domain and C-terminal leucine zipper. Here, we discuss how TbBILBO1 might assemble at the flagellar pocket collar in T. brucei. PMID- 26844755 TI - In vitro activity of 3beta-O-tigloylmelianol from Guarea kunthiana A. Juss (Meliaceae) on oogenesis and ecdysis of the cattle tick Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae). AB - We evaluated the effects of 3beta-O-tigloylmelianol from Guarea kunthiana A. Juss (Meliaceae) on oogenesis, as a larvicide and on ecdysis of the larvae and the nymphs of the cattle tick Rhipicephalus (Boophilus) microplus (Canestrini) (Acari: Ixodidae). On the oogenesis' test, 48 engorged females were divided into three groups, evaluated at 24, 48 and 72 h post-treatment. Half of the females were treated with 0.01% 3beta-O-tigloylmelianol diluted in distilled water and 5% dimethyl sulfoxide (DMSO), while the other half (controls) were exposed to distilled water and 5% DMSO. After treatment, the ovaries were weighed in order to measure the gonadosomatic index (GSI) and were also subjected to standard histological technical tests. On the larvicide and ecdysis' tests, 3beta-O tigloylmelianol was tested at concentrations of 0.01, 0.005, 0.0025 and 0.00125%. Compared with the controls, there was a reduction of GSI of approximately 50% on the treated group, which started at 48 h post treatment. Overall, the protolimonoid 3beta-O-tigloylmelianol has caused a significant reduction in the number of oocytes. It has also caused alteration of the cytoplasmic and germinal vesicle diameters. Morphological changes, such as vacuolization, chorion irregularity which has modified the oocytes' morphology as well as alterations on the yolk's granules were also observed. The compound was not larvicide, however, interfered in the ecdysis of the larvae and the nymphs. This study shows that the protolimonoid 3beta-O-tigloylmelianol from G. kunthiana acts on oogenesis and ecdysis of R. (B.) microplus, but not as larvicide, indicating that it acts on the endocrine system of the tick. PMID- 26844757 TI - Effectiveness of doxylamine-pyridoxine for morning sickness. PMID- 26844756 TI - Keloids: The paradigm of skin fibrosis - Pathomechanisms and treatment. AB - Keloids, fibroproliferative dermal tumors with effusive accumulation of extracellular matrix (ECM) components, particularly collagen, result from excessive expression of growth factors and cytokines. The etiology of keloids is unknown but they occur after dermal injury in genetically susceptible individuals, and they cause both physical and psychological distress for the affected individuals. Several treatment methods for keloids exist, including the combination therapy of surgical excision followed by intralesional steroid therapy, however, they have high recurrence rate regardless of the current treatment method. Improved understanding of the pathomechanisms leading to keloid formation will hopefully identify pathways that serve as specific targets to improve therapy for this devastating, currently intractable, disorder. PMID- 26844758 TI - Clinical management of medications in pregnancy and lactation. AB - Prescription and over-the-counter medication use during pregnancy and lactation is exceedingly common. There are many available resources to gather information and guide patient counseling. These include primary literature, online resources, professional society recommendations, and drug labels. One must consider both disease and drug characteristics when making decisions on medication use during pregnancy and lactation. Providers can then use this information to balance the risks of fetal or neonatal exposure against the potential benefits of maternal treatment and the risks of untreated disease. PMID- 26844760 TI - Developing EHR-driven heart failure risk prediction models using CPXR(Log) with the probabilistic loss function. AB - Computerized survival prediction in healthcare identifying the risk of disease mortality, helps healthcare providers to effectively manage their patients by providing appropriate treatment options. In this study, we propose to apply a classification algorithm, Contrast Pattern Aided Logistic Regression (CPXR(Log)) with the probabilistic loss function, to develop and validate prognostic risk models to predict 1, 2, and 5year survival in heart failure (HF) using data from electronic health records (EHRs) at Mayo Clinic. The CPXR(Log) constructs a pattern aided logistic regression model defined by several patterns and corresponding local logistic regression models. One of the models generated by CPXR(Log) achieved an AUC and accuracy of 0.94 and 0.91, respectively, and significantly outperformed prognostic models reported in prior studies. Data extracted from EHRs allowed incorporation of patient co-morbidities into our models which helped improve the performance of the CPXR(Log) models (15.9% AUC improvement), although did not improve the accuracy of the models built by other classifiers. We also propose a probabilistic loss function to determine the large error and small error instances. The new loss function used in the algorithm outperforms other functions used in the previous studies by 1% improvement in the AUC. This study revealed that using EHR data to build prediction models can be very challenging using existing classification methods due to the high dimensionality and complexity of EHR data. The risk models developed by CPXR(Log) also reveal that HF is a highly heterogeneous disease, i.e., different subgroups of HF patients require different types of considerations with their diagnosis and treatment. Our risk models provided two valuable insights for application of predictive modeling techniques in biomedicine: Logistic risk models often make systematic prediction errors, and it is prudent to use subgroup based prediction models such as those given by CPXR(Log) when investigating heterogeneous diseases. PMID- 26844761 TI - mTORC1 alters the expression of glycolytic genes by regulating KPNA2 abundances. AB - Mammalian target of rapamycin complex 1 (mTORC1) plays important roles in regulating cell growth and proliferation, and the aberrant activation of mTORC1 has been observed in many human diseases. However, the proteins regulated by mTORC1 activation and their roles in mTORC1 downstream functions are still poorly understood. Using proteomic analysis, we found that proteins regulated by mTORC1 in MEFs could be categorized into eight functional groups including protein nuclear import and glycolysis. The positive regulation of Karyopherin subunit alpha-2 (KPNA2), an importer protein involved in protein nuclear import, by mTORC1 was verified in several other mouse and human cell lines. The regulation occurred at the transcriptional level, rather than at the level of S6K1- and 4E BP1-dependent protein synthesis. KPNA2 knockdown partially blocked upregulation of glycolytic genes by mTORC1 activation, indicating that mTORC1 activation enhanced expression of glycolytic genes by increasing KPNA2 abundances. Furthermore, KPNA2 knockdown had no effects on the expression and subcellular localization of HIF1alpha, a transcription factor involved in regulating glycolytic genes downstream of mTORC1. In conclusion, our results proved that KPNA2 regulated the expression of glycolytic genes downstream of mTORC1 in a HIF1alpha-independent manner. SIGNIFICANCE: Identifying mTORC1-regulated proteins through proteomic method is a feasible way to study the downstream functions of mTORC1. In this study, we identified many mTORC1-regulated proteins using proteomic analysis by overlapping two different high vs low/no mTORC1 activity comparisons, TSC2(-/-) vs WT MEFs and TSC2(-/-) with/without rapamycin treatment. We found the abundances of many enzymes in glycolysis pathway and several proteins involved in protein nuclear import were positively regulated by mTORC1. More importantly, we first discovered that mTORC1 positively regulated the importer protein KPNA2, which participated in glycolysis regulation downstream of mTORC1 in a HIF1alpha-independent manner, indicating that mTORC1 regulates glycolysis through multiple ways. PMID- 26844762 TI - Epigenetic Activation of Antibacterial Property of an Endophytic Streptomyces coelicolor Strain AZRA 37 and Identification of the Induced Protein Using MALDI TOF MS/MS. AB - The endophytic Streptomyces coelicolor strain AZRA 37 was isolated from the surface sterilized root of Azadirachta indica A. Juss., commonly known as neem plant in India. Since only a few reports are available regarding epigenetic modulations of microbial entities, S. coelicolor was treated with different concentrations of 5-azacytidine for this purpose and evaluated for its antibacterial potential against five human pathogenic bacteria (Aeromonas hydrophila IMS/GN11, Enterococcus faecalis IMS/GN7, Salmonella typhi MTCC 3216, Shigella flexneri ATCC 12022 and Staphylococcus aureus ATCC 25923). The crude extract obtained from cultures treated with 25 MUM concentration of 5 azacytidine, was found effective against all five pathogenic bacteria tested while the untreated control was only active against 3 pathogenic bacteria. HPLC analysis of crude compounds from treated cultures showed a greater number of compounds than that of the control. Extraction of whole cell protein and its SDS PAGE analysis showed an additional major protein band in 25 MUM 5-azacytidine treated culture and MALDI TOF MS/MS analysis revealed that this protein belongs to the porin family. PMID- 26844763 TI - ErbB4 Gene Polymorphism Is Associated With the Risk and Prognosis of Congestive Heart Failure in a Northern Han Chinese Population. AB - BACKGROUND: There has been no research evaluating the association between human Neuregulin (NRG) 1/ErbB2/ErbB4 gene polymorphisms and heart failure risk. METHODS AND RESULTS: Genotyping of 13 single nucleotide polymorphisms (SNPs) in the NRG 1/ErbB2/ErbB4 genes was performed in 569 unrelated heart failure patients and 682 healthy controls from a Northern Han Chinese population with the use of iPlex SNP Genotyping analysis on a Sequenom Massarray System. In the ErbB4 gene, the variants rs10932374 and rs1595064 were associated with reduced risk of heart failure under allelic, recessive and additive genetic models, and the variants rs13003941 and rs1595065 were associated with increased risk of heart failure under allelic, dominant, and additive models. The G-G-C-C-T haplotype of rs10932374-rs13003941-rs1595064-rs1595065-rs3748960 in the ErbB4 gene increased the risk of heart failure (odd ratio 1.35, 95% confidence interval [CI] 1.06 1.70; P = .014). The T variant of rs13003941 was associated with larger left ventricle (dominant model, P = .014; additive model, P = .048), and increased risk of overall death (relative risk [RR] 1.48, 95% CI 1.01-2.18; P = .045) and cardiovascular death (RR 1.56, 95% CI 1.04-2.33; P = .03) after adjusting for age and sex. NRG-1/ErbB2 gene polymorphisms were not associated with heart failure risk or prognosis. CONCLUSION: ErbB4 gene polymorphisms were associated with the risk, severity, and prognosis of heart failure in a Northern Han Chinese population. PMID- 26844759 TI - The therapeutic potential of cell identity reprogramming for the treatment of aging-related neurodegenerative disorders. AB - Neural cell identity reprogramming strategies aim to treat age-related neurodegenerative disorders with newly induced neurons that regenerate neural architecture and functional circuits in vivo. The isolation and neural differentiation of pluripotent embryonic stem cells provided the first in vitro models of human neurodegenerative disease. Investigation into the molecular mechanisms underlying stem cell pluripotency revealed that somatic cells could be reprogrammed to induced pluripotent stem cells (iPSCs) and these cells could be used to model Alzheimer disease, amyotrophic lateral sclerosis, Huntington disease, and Parkinson disease. Additional neural precursor and direct transdifferentiation strategies further enabled the induction of diverse neural linages and neuron subtypes both in vitro and in vivo. In this review, we highlight neural induction strategies that utilize stem cells, iPSCs, and lineage reprogramming to model or treat age-related neurodegenerative diseases, as well as, the clinical challenges related to neural transplantation and in vivo reprogramming strategies. PMID- 26844765 TI - The Added Value of Exercise Variables in Heart Failure Prognosis. AB - INTRODUCTION: Diminished exercise capacity is a key symptom in heart failure (HF). Exercise predictors (peak VO2, VE/VCO2 slope, and oxygen uptake efficiency slope [OUES]) are prognostic markers but studied in isolation. We evaluated if these exercise variables offer additional prognostic value to clinical predictors in HF. METHODS AND RESULTS: This was a single-institution retrospective cohort study of 517 consecutive HF patients. We used Cox proportional hazards modeling to determine the additional prognostic value of exercise variables on mortality, HF hospital admissions, and a composite outcome of ventricular assistance device (VAD) implantation, heart transplantation (HT), and death. During a mean follow up of 2.7 years, 52 deaths, 47 HTs, and 19 VAD implantations occurred. After adjusting for age, New York Heart Association functional class, ejection fraction, body mass index, creatinine, and B-type natriuretic peptide, peak VO2 (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.85-0.96), OUES (HR 0.92, 95% CI 0.87-0.97), and VE/VCO2 (HR 1.03, 95% CI 1.01-1.05) were independent predictors of the composite outcome. Similar discriminatory capacity existed between the exercise variables (c-statistics 0.77, 0.78, and 0.78, respectively). Only VE/VCO2 was an independent predictor of admissions (HR 1.04, 95% CI 1.01 1.07), and only peak VO2 was an independent predictor of mortality (HR 0.90, 95% CI 0.84-0.98). CONCLUSIONS: Peak VO2, OUES, and VE/VCO2 are independent predictors of HF prognosis over recognized clinical variables. However, no single exercise variable was superior. PMID- 26844764 TI - Clinical Implications of Serum Albumin Levels in Acute Heart Failure: Insights From DOSE-AHF and ROSE-AHF. AB - BACKGROUND: Hypoalbuminemia is common in patients with chronic heart failure and, as a marker of disease severity, is associated with an adverse prognosis. Whether hypoalbuminemia contributes to (or is associated with) worse outcomes in acute heart failure (AHF) is unclear. We sought to determine the implications of low serum albumin in patients receiving decongestive therapies for AHF. METHODS AND RESULTS: Baseline serum albumin levels were measured in 456 AHF subjects randomized in the DOSE-AHF and ROSE-AHF trials. We assessed the relationship between admission albumin levels (both as a continuous variable and stratified by median albumin [>=3.5 g/dL]) and worsening renal function (WRF), worsening heart failure (WHF), and clinical decongestion by 72 hours; 7-day cardiorenal biomarkers; and post-discharge outcomes. The mean baseline albumin level was 3.5 +/- 0.5 g/dL. Albumin was not associated with WRF, WHF, or clinical decongestion by 72 hours. Furthermore, there was no association between continuous albumin levels and symptom change according to visual analog scale or weight change by 72 hours. Albumin was not associated with 60-day mortality, rehospitalization, or unscheduled emergency room visits. CONCLUSIONS: Baseline serum albumin levels were not associated with short-term clinical outcomes for AHF patients undergoing decongestive therapies. These data suggest that serum albumin may not be a helpful tool to guide decongestion strategies. PMID- 26844766 TI - Cell Death in the Epithelia of the Intestine and Hepatopancreas in Neocaridina heteropoda (Crustacea, Malacostraca). AB - The endodermal region of the digestive system in the freshwater shrimp Neocaridina heteropoda (Crustacea, Malacostraca) consists of a tube-shaped intestine and large hepatopancreas, which is formed by numerous blind-ended tubules. The precise structure and ultrastructure of these regions were presented in our previous studies, while here we focused on the cell death processes and their effect on the functioning of the midgut. We used transmission electron microscopy, light and confocal microscopes to describe and detect cell death, while a quantitative assessment of cells with depolarized mitochondria helped us to establish whether there is the relationship between cell death and the inactivation of mitochondria. Three types of the cell death were observed in the intestine and hepatopancreas-apoptosis, necrosis and autophagy. No differences were observed in the course of these processes in males and females and or in the intestine and hepatopancreas of the shrimp that were examined. Our studies revealed that apoptosis, necrosis and autophagy only involves the fully developed cells of the midgut epithelium that have contact with the midgut lumen-D-cells in the intestine and B- and F-cells in hepatopancreas, while E-cells (midgut stem cells) did not die. A distinct correlation between the accumulation of E-cells and the activation of apoptosis was detected in the anterior region of the intestine, while necrosis was an accidental process. Degenerating organelles, mainly mitochondria were neutralized and eventually, the activation of cell death was prevented in the entire epithelium due to autophagy. Therefore, we state that autophagy plays a role of the survival factor. PMID- 26844768 TI - Correction: Human Milk Warming Temperatures Using a Simulation of Currently Available Storage and Warming Methods. PMID- 26844767 TI - Acute Systemic Infection with Dengue Virus Leads to Vascular Leakage and Death through Tumor Necrosis Factor-alpha and Tie2/Angiopoietin Signaling in Mice Lacking Type I and II Interferon Receptors. AB - Severe dengue is caused by host responses to viral infection, but the pathogenesis remains unknown. This is, in part, due to the lack of suitable animal models. Here, we report a non-mouse-adapted low-passage DENV-3 clinical isolate, DV3P12/08, derived from recently infected patients. DV3P12/08 caused a lethal systemic infection in type I and II IFN receptor KO mice (IFN alpha/beta/gammaR KO mice), which have the C57/BL6 background. Infection with DV3P12/08 induced a cytokine storm, resulting in severe vascular leakage (mainly in the liver, kidney and intestine) and organ damage, leading to extensive hemorrhage and rapid death. DV3P12/08 infection triggered the release of large amounts of TNF-alpha, IL-6, and MCP-1. Treatment with a neutralizing anti-TNF alpha antibody (Ab) extended survival and reduced liver damage without affecting virus production. Anti-IL-6 neutralizing Ab partly prolonged mouse survival. The anti-TNF-alpha Ab suppressed IL-6, MCP-1, and IFN-gamma levels, suggesting that the severe response to infection was triggered by TNF-alpha. High levels of TNF alpha mRNA were expressed in the liver and kidneys, but not in the small intestine, of infected mice. Conversely, high levels of IL-6 mRNA were expressed in the intestine. Importantly, treatment with Angiopoietin-1, which is known to stabilize blood vessels, prolonged the survival of DV3P12/08-infected mice. Taken together, the results suggest that an increased level of TNF-alpha together with concomitant upregulation of Tie2/Angiopoietin signaling have critical roles in severe dengue infection. PMID- 26844770 TI - A Dual Tracer 18F-FCH/18F-FDG PET Imaging of an Orthotopic Brain Tumor Xenograft Model. AB - Early diagnosis of low grade glioma has been a challenge to clinicians. Positron Emission Tomography (PET) using 18F-FDG as a radio-tracer has limited utility in this area because of the high background in normal brain tissue. Other radiotracers such as 18F-Fluorocholine (18F-FCH) could provide better contrast between tumor and normal brain tissue but with high incidence of false positives. In this study, the potential application of a dual tracer 18F-FCH/18F-FDG-PET is investigated in order to improve the sensitivity of PET imaging for low grade glioma diagnosis based on a mouse orthotopic xenograft model. BALB/c nude mice with and without orthotopic glioma xenografts from U87 MG-luc2 glioma cell line are used for the study. The animals are subjected to 18F-FCH and 18F-FDG PET imaging, and images acquired from two separate scans are superimposed for analysis. The 18F-FCH counts are subtracted from the merged images to identify the tumor. Micro-CT, bioluminescence imaging (BLI), histology and measurement of the tumor diameter are also conducted for comparison. Results show that there is a significant contrast in 18F-FCH uptake between tumor and normal brain tissue (2.65 +/- 0.98), but with a high false positive rate of 28.6%. The difficulty of identifying the tumor by 18F-FDG only is also proved in this study. All the tumors can be detected based on the dual tracer technique of 18F-FCH/18F-FDG-PET imaging in this study, while the false-positive caused by 18F-FCH can be eliminated. Dual tracer 18F-FCH/18F-FDG PET imaging has the potential to improve the visualization of low grade glioma. 18F-FCH delineates tumor areas and the tumor can be identified by subtracting the 18F-FCH counts. The sensitivity was over 95%. Further studies are required to evaluate the possibility of applying this technique in clinical trials. PMID- 26844769 TI - MicroRNAs Form Triplexes with Double Stranded DNA at Sequence-Specific Binding Sites; a Eukaryotic Mechanism via which microRNAs Could Directly Alter Gene Expression. AB - MicroRNAs are important regulators of gene expression, acting primarily by binding to sequence-specific locations on already transcribed messenger RNAs (mRNA) and typically down-regulating their stability or translation. Recent studies indicate that microRNAs may also play a role in up-regulating mRNA transcription levels, although a definitive mechanism has not been established. Double-helical DNA is capable of forming triple-helical structures through Hoogsteen and reverse Hoogsteen interactions in the major groove of the duplex, and we show physical evidence (i.e., NMR, FRET, SPR) that purine or pyrimidine rich microRNAs of appropriate length and sequence form triple-helical structures with purine-rich sequences of duplex DNA, and identify microRNA sequences that favor triplex formation. We developed an algorithm (Trident) to search genome wide for potential triplex-forming sites and show that several mammalian and non mammalian genomes are enriched for strong microRNA triplex binding sites. We show that those genes containing sequences favoring microRNA triplex formation are markedly enriched (3.3 fold, p<2.2 * 10(-16)) for genes whose expression is positively correlated with expression of microRNAs targeting triplex binding sequences. This work has thus revealed a new mechanism by which microRNAs could interact with gene promoter regions to modify gene transcription. PMID- 26844771 TI - Substantial Downregulation of Myogenic Transcripts in Skeletal Muscle of Atlantic Cod during the Spawning Period. AB - Gonadal maturation is an extremely energy consuming process for batch spawners and it is associated with a significant decrease in growth and seasonal deterioration in flesh quality. Our knowledge about the molecular mechanisms linking sexual maturation and muscle growth is still limited. In the present study, we performed RNA-Seq using 454 GS-FLX pyrosequencing in fast skeletal muscle sampled from two-year-old Atlantic cod (Gadus morhua) at representative time points throughout the reproductive cycle (August, March and May). In total, 126,937 good quality reads were obtained, with 546 nucleotide length and 52% GC content on average. RNA-Seq analysis using the CLC Genomics Workbench with the Atlantic cod reference UniGene cDNA data revealed 59,581 (46.9%) uniquely annotated reads. Pairwise comparison for expression levels identified 153 differentially expressed UniGenes between time points. Notably, we found a significant suppression of myh13 and myofibrillar gene isoforms in fast skeletal muscle during the spawning season. This study uncovered a large number of differentially expressed genes that may be influenced by gonadal maturation, thus representing a significant contribution to our limited understanding of the molecular mechanisms regulating muscle wasting and regeneration in batch spawners during their reproductive cycle. PMID- 26844772 TI - Current Perspectives on Plague Vector Control in Madagascar: Susceptibility Status of Xenopsylla cheopis to 12 Insecticides. AB - Plague is a rodent disease transmissible to humans by infected flea bites, and Madagascar is one of the countries with the highest plague incidence in the world. This study reports the susceptibility of the main plague vector Xenopsylla cheopis to 12 different insecticides belonging to 4 insecticide families (carbamates, organophosphates, pyrethroids and organochlorines). Eight populations from different geographical regions of Madagascar previously resistant to deltamethrin were tested with a World Health Organization standard bioassay. Insecticide susceptibility varied amongst populations, but all of them were resistant to six insecticides belonging to pyrethroid and carbamate insecticides (alphacypermethrin, lambdacyhalothrin, etofenprox, deltamethrin, bendiocarb and propoxur). Only one insecticide (dieldrin) was an efficient pulicide for all flea populations. Cross resistances were suspected. This study proposes at least three alternative insecticides (malathion, fenitrothion and cyfluthrin) to replace deltamethrin during plague epidemic responses, but the most efficient insecticide may be different for each population studied. We highlight the importance of continuous insecticide susceptibility surveillance in the areas of high plague risk in Madagascar. PMID- 26844773 TI - Redox cycling metals: Pedaling their roles in metabolism and their use in the development of novel therapeutics. AB - Essential metals, such as iron and copper, play a critical role in a plethora of cellular processes including cell growth and proliferation. However, concomitantly, excess of these metal ions in the body can have deleterious effects due to their ability to generate cytotoxic reactive oxygen species (ROS). Thus, the human body has evolved a very well-orchestrated metabolic system that keeps tight control on the levels of these metal ions. Considering their very high proliferation rate, cancer cells require a high abundance of these metals compared to their normal counterparts. Interestingly, new anti-cancer agents that take advantage of the sensitivity of cancer cells to metal sequestration and their susceptibility to ROS have been developed. These ligands can avidly bind metal ions to form redox active metal complexes, which lead to generation of cytotoxic ROS. Furthermore, these agents also act as potent metastasis suppressors due to their ability to up-regulate the metastasis suppressor gene, N myc downstream regulated gene 1. This review discusses the importance of iron and copper in the metabolism and progression of cancer, how they can be exploited to target tumors and the clinical translation of novel anti-cancer chemotherapeutics. PMID- 26844774 TI - Roads to melanoma: Key pathways and emerging players in melanoma progression and oncogenic signaling. AB - Melanoma has markedly increased worldwide during the past several decades in the Caucasian population and is responsible for 80% of skin cancer deaths. Considering that metastatic melanoma is almost completely resistant to most current therapies and is linked with a poor patient prognosis, it is crucial to further investigate potential molecular targets. Major cell-autonomous drivers in the pathogenesis of this disease include the classical MAPK (i.e., RAS-RAF-MEK ERK), WNT, and PI3K signaling pathways. These pathways play a major role in defining the progression of melanoma, and some have been the subject of recent pharmacological strategies to treat this belligerent disease. This review describes the latest advances in the understanding of melanoma progression and the major molecular pathways involved. In addition, we discuss the roles of emerging molecular players that are involved in melanoma pathogenesis, including the functional role of the melanoma tumor antigen, p97/MFI2 (melanotransferrin). PMID- 26844775 TI - IgG Expression upon Oral Sensitization in Association with Maternal Exposure to Ovalbumin. AB - The role of maternal allergen exposure in the allergenicity of the offspring remains controversial. Some studies have shown that maternal exposure is a risk factor for allergy in the offspring, whereas other studies have shown that maternal exposure induces immune tolerance and protects offspring from allergy disease. Therefore, we utilized maternal rat allergen exposure model to evaluate the offspring immune reactions to ovalbumin protein and to determine whether the Brown Norway (BN) rat model is a suitable animal model for studying the allergenicity of food proteins. For three generations, rats received an allergens or non-allergens by gavage during the pregnancy and lactation periods. After weaning, the offspring rats were used for oral sensitization experiment. In the sensitization experiment, the control rat, which had maternal exposure to phosphate-buffered saline (PBS), exhibited full response of IgG to oral exposure to OVA. The IgG level was significantly lower in F1 rats that were sensitized by maternal exposure to ovalbumin(OVA). Moreover, the lowest IgG level was found for the F3b sensitized by maternal rats exposed to OVA allergen for three continuous generations. Compared with maternal OVA exposure prior to postnatal sensitization, the sensitization via maternal PBS led to a higher serum level of OVA-specific IgG. However, the OVA-specific IgG levels for the two generations of maternal PBS exposure prior to postnatal sensitization was not higher than that for the one generation of maternal rats exposed to PBS prior to postnatal sensitization. Our studies demonstrate that maternal OVA exposure during the pregnancy and lactation can affect the results of oral sensitization studies using ovalbumin protein. BN rats must be bred in non-allergen conditions for at least one generation to avoid problems in rat models for studying the allergenicity of food proteins. PMID- 26844777 TI - Renal Biopsy in 2015--From Epidemiology to Evidence-Based Indications. AB - BACKGROUND: Although the number of patients reaching end-stage kidney disease without a biopsy-proven diagnosis is increasing, the utility of renal biopsy is still an object of debate. We analyzed epidemiological data and the main indications for renal biopsy with a systematic, evidence-based review at current literature. SUMMARY: There is a high discrepancy observed in biopsy rates and in the epidemiology of glomerular diseases worldwide, related to the different time frame of the analyzed reports, lack of data collection, the different reference source population and the heterogeneity of indications. The evidence-based analysis of indications showed that renal biopsy should be crucial in adults with nephrotic syndrome or urinary abnormalities as coexistent hematuria and proteinuria and in corticosteroid resistant-children with severe proteinuria. The knowledge of renal histology can change the clinical management in patients with acute kidney injury significantly, after the exclusion of pre-renal or obstructive causes of kidney damage. Scarce evidence indicates that renal biopsy can be useful in patients with advanced chronic kidney disease and its use should always be considered after weighing the benefits and potential risks. Renal biopsy should be crucial in patients with renal involvement due to systemic disease. In patients with diabetes with atypical features, renal biopsy may be fundamental to diagnose an unexpected parenchymal disease mislabeled as diabetic nephropathy. Finally, in elderly patients, the indications and the risks are not different from those in the general population. KEY MESSAGE: Renal biopsy still remains a concrete approach for managing a substantial percentage of renal diseases. PMID- 26844776 TI - The Enzymatic Paradox of Yeast Arginyl-tRNA Synthetase: Exclusive Arginine Transfer Controlled by a Flexible Mechanism of tRNA Recognition. AB - Identity determinants are essential for the accurate recognition of transfer RNAs by aminoacyl-tRNA synthetases. To date, arginine determinants in the yeast Saccharomyces cerevisiae have been identified exclusively in vitro and only on a limited number of tRNA Arginine isoacceptors. In the current study, we favor a full cellular approach and expand the investigation of arginine determinants to all four tRNA Arg isoacceptors. More precisely, this work scrutinizes the relevance of the tRNA nucleotides at position 20, 35 and 36 in the yeast arginylation reaction. We built 21 mutants by site-directed mutagenesis and tested their functionality in YAL5, a previously engineered yeast knockout deficient for the expression of tRNA Arg CCG. Arginylation levels were also monitored using Northern blot. Our data collected in vivo correlate with previous observations. C35 is the prominent arginine determinant followed by G36 or U36 (G/U36). In addition, although there is no major arginine determinant in the D loop, the recognition of tRNA Arg ICG relies to some extent on the nucleotide at position 20. This work refines the existing model for tRNA Arg recognition. Our observations indicate that yeast Arginyl-tRNA synthetase (yArgRS) relies on distinct mechanisms to aminoacylate the four isoacceptors. Finally, according to our refined model, yArgRS is able to accommodate tRNA Arg scaffolds presenting N34, C/G35 and G/A/U36 anticodons while maintaining specificity. We discuss the mechanistic and potential physiological implications of these findings. PMID- 26844779 TI - Validation and Cultural Adaptation of the Arabic Version of the Eating Assessment Tool (EAT-10). AB - BACKGROUND AND OBJECTIVES: The Eating Assessment Tool (EAT-10) is a 10-item self administered questionnaire. It is a noninvasive tool to measure patients' perception of their swallowing problems. The purposes of the present study were to develop an Arabic version of the EAT-10 and to evaluate its validity, consistency, and reliability in the Arabic-speaking population with oropharyngeal dysphagia. SETTING AND DESIGN: This was a prospective study carried out at the Communication and Swallowing Disorders Unit, King Saud University, Riyadh, Saudi Arabia. SUBJECTS AND METHODS: The Arabic EAT-10 was administered to 138 patients with oropharyngeal dysphagia and 83 control subjects. Internal consistency and test-retest reliability were evaluated. Content and clinical validity were studied, and the EAT-10 results were compared across patients and control groups. RESULTS: The Arabic EAT-10 showed excellent internal consistency (Cronbach's alpha = 0.92). Also, good test-retest reliability was found for the total scores of the Arabic EAT-10 (intraclass correlation = 0.73). There was a significant difference in Arabic EAT-10 scores between the oropharyngeal dysphagia group and the control group (p < 0.001). CONCLUSION: This study demonstrated that the Arabic EAT-10 is a valid tool that can be used for screening of dysphagia-related problems in an Arabic-speaking population. PMID- 26844778 TI - Interferon-Stimulated Gene 15, a Type I Interferon-Dependent Transcript, Is Involved in a Negative Feedback Loop in Innate Immune Reactions in Human Mesangial Cells. AB - BACKGROUND: Since innate immunity plays a pivotal role in the pathogenesis of glomerulonephritis, the activation of toll-like receptor (TLR) 3/type I interferon (IFN) cascades is important in glomerular inflammation. However, the role of IFN-stimulated gene 15 (ISG15), a type IFN-dependent transcript, in glomerular inflammation is unclear. We, therefore, examined the role of ISG15 in innate immune reactions induced by TLR3 signaling in cultured human mesangial cells (MCs). METHODS: We treated MCs with polyinosinic-polycytidylic acid (poly IC), an authentic double-stranded RNA, and analyzed the ISG15 expression by reverse transcription-polymerase chain reaction and western blotting. To examine the regulation of ISG15 expression, we subjected MCs to RNA interference (siRNA) against TLR3, IFN-beta, ISG56, and melanoma differentiation-associated gene 5 (MDA5). RESULTS: ISG15 expression induced by poly IC in MCs was inhibited by siRNA against TLR3 and IFN-beta, whereas silencing of ISG56 or MDA5 had no effect. A knockdown of ISG15 upregulated the expression of ISG56, MDA5, CXCL10 and phosphorylated signal transducers and activators of transcription protein 1 (P-STAT1), while a knockdown of ubiquitin-like modifier activating enzyme 7, a key enzyme that conjugates ISG15 to target proteins, did not affect the expression. Knockdown of ubiquitin specific protease 18, an ISG15 isopeptidase, also upregulated P-STAT1, ISG56, MDA5 and CXCL10. CONCLUSION: Since unconjugated free ISG15 negatively regulates the phosphorylation of STAT1 and its downstream reactions, ISG15 dysregulation may be involved in the pathogenesis of glomerular inflammation. We believe that suitable interventions in these innate immune cascades is desirable for the future therapeutic strategies for glomerulonephritis. PMID- 26844780 TI - Differential proteomic response of Sydney rock oysters (Saccostrea glomerata) to prolonged environmental stress. AB - Exposure to prolonged environmental stress can have impacts on the cellular homeostasis of aquatic organisms. The current study employed two-dimensional electrophoresis (2-DE) to test whether exposure to impaired water quality conditions in the Sydney Harbour estuary has significantly altered the proteomes of the resident Sydney rock oyster (Saccostrea glomerata). Adult S. glomerata were sampled from four bays in the estuary. Each bay consisted of a "high-impact" site adjacent to point sources of chemical contamination (e.g., storm drains/canals or legacy hotspots) and a "low-impact" site located ~5km away from point sources. A mixture of environmental stressors differed significantly between high- and low-impact sites. Specifically, PAHs, PCBs, tributyltin, Pb, and Zn were significantly elevated in oyster tissues from high-impact sites, together with depleted dissolved oxygen and low pH in the water column. A 2-DE proteomics analysis subsequently identified 238 protein spots across 24 2-DE gels, of which 27-50 spots differed significantly in relative intensity between high- and low-impact sites per bay. Twenty-five percent of the differential spots were identified in more than one bay. The identities of 80 protein spots were determined by mass spectrometry. HSP 70, PPIB, and radixin were the three most highly expressed differential proteins. Despite the largely unique proteomes evident in each bay, functional annotations revealed that half of the differentially expressed proteins fell into just two subcellular functional categories-energy metabolism and the cytoskeleton. These findings provide a framework to further investigate adaptation of cellular mechanisms to prolonged stress in S. glomerata. PMID- 26844781 TI - High cryptic soil ciliate (Ciliophora, Hypotrichida) diversity in Australia. AB - The diversity and distribution of soil ciliates from Australia is poorly known. Thus, we studied eight taxa, using the non-flooded Petri dish culture method, live observation, silver impregnation, detailed morphometrics, ontogenesis, and reinvestigation of type slides. At first glance, the Australian taxa looked very similar to described species, however, detailed investigations resulted in the identification of six cryptic species: Afroamphisiella multinucleata minima nov. subspec., Cladotricha similis nov. spec., Erimophrya similis nov. spec., Heterogonostomum salinarum nov. gen., nov. spec., Pseudohemisincirra arabica australiensis nov. subspec., and Pattersoniella (Pattersoniellides) australiensis nov. subgen., nov. spec. This new subgenus is unique among all described hypotrichs in having reduced some anterior paroral dikinetids the fibrillar associates of which are, however, still present. Only two of the eight taxa are possibly cosmopolitans: Apourosomoida halophilaFoissner et al., 2002 and Urosoma karinaeFoissner, 1987. This supports the moderate endemicity model, i.e., that a third of protists have a restricted distribution (Foissner, Chao and Katz 2008). PMID- 26844782 TI - Effect through inhalation on human health of PM1 bound polycyclic aromatic hydrocarbons collected from foggy days in northern part of India. AB - We investigated the health risk from 16 polycyclic aromatic hydrocarbons (PAHs) adsorbed on submicron particles and also reported their concentrations, spatial distribution and possible sources during foggy days at Kanpur. Twenty-four urban foggy day's samples gathered from Kanpur, an urban center in North India and most densely populated city in the Indo-Gangetic plain of India, were examined for 16 PAHs (2-6 rings).The mean concentration of PM1 was found to be 160.16+/ 37.70MUg/m(3). ?16PAHs concentrations were 529.17ng/m(3) with a mean of 33.07ng/m(3). The compounds of higher molecular weight (4-6 rings) added to 70.67% of ?PAHs mass concentration in the foggy day's samples. The results of source identification by using principle component analysis (PCA) and diagnostic ratios proposed that the primary sources of PAHs were vehicular emission (primarily driven by diesel fuel) and coal combustion and the secondary source. Exposure to total PAHs in the ambient air resulted in, 95% probability total Incremental Lifetime Cancer Risk (TILCR) 3.57*10(-5) for adults and 2.08*10(-5) for children or (~35 cancer case per million in adults and ~20 cancer case per million in children) due to inhalation in terms of ILCR were higher than the baseline value of acceptable risk (one cancer case per million people) suggesting moderate health risk to resident human population. PMID- 26844783 TI - Silylation of leached-vermiculites following reaction with imidazole and copper sorption behavior. AB - Organically modified vermiculites were synthesized by previous silylation of three leached vermiculites, V0.3Cl, V0.5Cl and V0.8Cl, under anhydrous conditions following reaction with imidazole (Im), which acted as chelating agent for copper retention. Elemental analysis, X-ray diffraction, infrared spectroscopy, scanning electronic microscopy, transmission electron microscopy, (29)Si and (13)C NMR and nitrogen adsorption/desorption measurements were used to characterize pristine, leached and organofunctionalized solids. X-ray photoelectron spectroscopy (XPS) was used to evaluate the surface after copper sorption. Parameters such as contact time, pH and initial cation concentration for the adsorption of Cu(II) ions were investigated. The adsorption equilibrium data were fitted using the Langmuir isotherm model and the monolayer adsorption capacities were 2.38, 2.52 and 2.69mmolg(-1) for V0.5Cl-Im, V0.3Cl-Im and V0.8Cl-Im, respectively, at pH 6.0 and 298K for a time reaction of 80min. The sorption rates were described by pseudo-second-order kinetics. The chloropropyl imidazole vermiculites are promising adsorbents for the rapid removal of Cu(II) ions from aqueous solution. PMID- 26844784 TI - Role of miR-155 in fluorooctane sulfonate-induced oxidative hepatic damage via the Nrf2-dependent pathway. AB - Studies demonstrated that perfluorooctane sulfonate (PFOS) tends to accumulate in the liver and is capable to cause hepatomegaly. In the present study, we investigated the roles of miR-155 in PFOS-induced hepatotoxicity in SD rats and HepG2 cells. Male SD rats were orally administrated with PFOS at 1 or 10mg/kg/day for 28 days while HepG2 cells were treated with 0-50 MUM of PFOS for 24h or 50 MUM of PFOS for 1, 3, 6, 12 or 24h, respectively. We found that PFOS significantly increased the liver weight and serum alanine transaminase (ALT) and aspartate amino transferase (AST) levels in rats. Morphologically, PFOS caused actin filament remodeling and endothelial permeability changes in the liver. Moreover, PFOS triggered reactive oxygen species (ROS) generation and induced apoptosis in both in vivo and in vitro assays. Immunoblotting data showed that NF E2-related factor-2 (Nrf2) expression and activation and its target genes were all suppressed by PFOS in the liver and HepG2 cells. However, PFOS significantly increased miR-155 expression. Further studies showed that pretreatment of HepG2 cells with catalase significantly decreased miR-155 expression and substantially increased Nrf2 expression and activation, resulting in reduction of PFOS-induced cytotoxicity and oxidative stress. Taken together, these results indicated that miR-155 plays an important role in the PFOS-induced hepatotoxicity by disrupting Nrf2/ARE signaling pathway. PMID- 26844785 TI - Pulmonary targeting potential of rosuvastatin loaded nanostructured lipid carrier: Optimization by factorial design. AB - Rosuvastatin (RSVS), an anti-lipidemic agent suggested for the treatment of airway remodeling in chronic obstructive pulmonary disease (COPD). It shows a pleiotropic effect on airway smooth muscles and inhibits proliferative activities of physiological mitogens. The aim of the present study was to develop and investigate the targeting potential of rosuvastatin (RSVS) to lung as loaded in nanostructured lipid carrier dry powder for inhalation (RNLC-DPI). RNLC dispersion was converted into respirable particle by lyophilization using 5% mannitol as cryoprotectant-carrier. Targeting efficiency of RNLC-DPI was evaluated in vitro for aerosol performance using 8-stage cascade impactor as well in vivo in Wistar rats for pulmokinetics. In vitro aerosol performance demonstrated mass median aerodynamic diameter of <3 MUm with fine particle fraction of >90% at 60 L/min. Improved aerosol performance was observed for RNLC DPI prepared using l-leucin as anti-static agent. Modified in vivo performance with higher Cmax (1.14-fold), improvement in t1/2 (5-fold) and 35-fold improvement in AUC0-infinity indicated significant improvement in bioavailability of RNLC-DPI. Lipidic nature and smaller size of particles helped in bypassing macrophage clearance leading to higher targeting factor. Thus, study demonstrated potential of RNLC-DPI for lung targeting and further for COPD treatment. PMID- 26844786 TI - Biopharmaceutical profile of hydrogels containing pranoprofen-loaded PLGA nanoparticles for skin administration: In vitro, ex vivo and in vivo characterization. AB - Pranoprofen (PF)-loaded nanoparticles (PF-F1NPs and PF-F2NPs) have been formulated into blank hydrogels (HG_PF-F1NPs and HG_PF-F1NPs) or into hydrogels composed of 3% azone (HG_PF-F1NPs-Azone and HG_PF-F2NPs-Azone), as innovative strategy to improve the biopharmaceutical profile of the selected non-steroidal anti-inflammatory drug (Pranoprofen, PF) for topical application. The purpose of this approach has been to increase the contact of PF with the skin, improve its retention in deeper layers, thus enhancing its anti-inflammatory and analgesic effects. The physicochemical characterization of the developed hydrogels showed a non-Newtonian behaviour, typical of semi-solid formulations for skin administration, with sustained release profile. The results obtained from ex vivo skin human permeation and in vivo anti-inflammatory efficacy studies suggest that topical application of HG_PF-F2NPs has been more effective in the treatment of oedema on the skin' surface in comparison to other hydrogels. No signs of skin irritancy have been detected for all the semi-solid formulations containing 0% or 3% azone. PMID- 26844787 TI - Quantification of vehicle fleet PM10 particulate matter emission factors from exhaust and non-exhaust sources using tunnel measurement techniques. AB - Road tunnels act like large laboratories; they provide an excellent environment to quantify atmospheric particles emission factors from exhaust and non-exhaust sources due to their known boundary conditions. Current work compares the High Volume, Dichotomous Stacked Filter Unit and Partisol Air Sampler for coarse, PM10 and PM2.5 particle concentration measurement and found that they do not differ significantly (p = 95%). PM2.5 fraction contributes 66% of PM10 proportions and significantly influenced by traffic (turbulence) and meteorological conditions. Mass emission factors for PM10 varies from 21.3 +/- 1.9 to 28.8 +/- 3.4 mg/vkm and composed of Motorcycle (0.0003-0.001 mg/vkm), Cars (26.1-33.4 mg/vkm), LDVs (2.4-3.0 mg/vkm), HDVs (2.2-2.8 mg/vkm) and Buses (0.1 mg/vkm). Based on Lawrence et al. (2013), source apportionment modelling, the PM10 emission of brake wear (3.8-4.4 mg/vkm), petrol exhaust (3.9-4.5 mg/vkm), diesel exhaust (7.2-8.3 mg/vkm), re-suspension (9-10.4 mg/vkm), road surface wear (3.9-4.5 mg/vkm), and unexplained (7.2 mg/vkm) were also calculated. The current study determined that the combined non-exhaust fleet PM10 emission factor (16.7-19.3 mg/vkm) are higher than the combined exhaust emission factor (11.1-12.8 mg/vkm). Thus, highlight the significance of non-exhaust emissions and the need for legislation and abatement strategies to reduce their contributions to ambient PM concentrations. PMID- 26844788 TI - Maternal Defense Mechanisms Influence Infant Development. PMID- 26844789 TI - Mothers, Babies, Depression, and Medications: Understanding the Complex Interplay of Illness and Treatment on Neonatal Symptoms. PMID- 26844790 TI - Community Evidence of Clozapine's Effectiveness. PMID- 26844791 TI - Dose Response for SSRIs. PMID- 26844792 TI - Clinical Experience With High-Dosage Pramipexole in Patients With Treatment Resistant Depressive Episodes in Unipolar and Bipolar Depression. PMID- 26844793 TI - A 39-Year-Old "Adultolescent": Understanding Social Withdrawal in Japan. PMID- 26844794 TI - Paul Gauguin, 1848-1903. PMID- 26844795 TI - Response to Rifkin. PMID- 26844796 TI - Reflections on "Addressing Patients' Psychic Pain". PMID- 26844797 TI - Outcome Variation in the Randomized Trial of Cognitive-Behavioral Therapy Versus Light Therapy for Seasonal Affective Disorder. PMID- 26844798 TI - Twitter Article Mentions and Citations: An Exploratory Analysis of Publications in the American Journal of Psychiatry. PMID- 26844802 TI - CORRECTION. PMID- 26844805 TI - Total Synthesis of the 7,10-Epimer of the Proposed Structure of Amphidinolide N, Part II: Synthesis of C17-C29 Subunit and Completion of the Synthesis. AB - The total synthesis of 7,10-epimer of the proposed structure of amphidinolide N was accomplished. The requisite chiral C17-C29 subunit was assembled stereoselectively via Keck allylation, Shi epoxidation, diastereoselective 1,3 reduction, and a later oxidative synthesis of the THF framework. The C1-C13 and C17-C29 subunits were successfully coupled using a Enders RAMP "linchpin" as the C14-C16 three carbon unit, thereby controlling the chirality at C14 and C16. The labile allyl epoxy moiety was successfully constructed by Grieco-Nishizawa olefination at a final stage of the synthesis. PMID- 26844804 TI - Unlocking neural complexity with a robotic key. AB - Complex brains evolved in order to comprehend and interact with complex environments in the real world. Despite significant progress in our understanding of perceptual representations in the brain, our understanding of how the brain carries out higher level processing remains largely superficial. This disconnect is understandable, since the direct mapping of sensory inputs to perceptual states is readily observed, while mappings between (unknown) stages of processing and intermediate neural states is not. We argue that testing theories of higher level neural processing on robots in the real world offers a clear path forward, since (1) the complexity of the neural robotic controllers can be staged as necessary, avoiding the almost intractable complexity apparent in even the simplest current living nervous systems; (2) robotic controller states are fully observable, avoiding the enormous technical challenge of recording from complete intact brains; and (3) unlike computational modelling, the real world can stand for itself when using robots, avoiding the computational intractability of simulating the world at an arbitrary level of detail. We suggest that embracing the complex and often unpredictable closed-loop interactions between robotic neuro-controllers and the physical world will bring about deeper understanding of the role of complex brain function in the high-level processing of information and the control of behaviour. PMID- 26844806 TI - Boosted Charge Transfer in SnS/SnO2 Heterostructures: Toward High Rate Capability for Sodium-Ion Batteries. AB - Constructing heterostructures can endow materials with fascinating performance in high-speed electronics, optoelectronics, and other applications owing to the built-in charge-transfer driving force, which is of benefit to the specific charge-transfer kinetics. Rational design and controllable synthesis of nano heterostructure anode materials with high-rate performance, however, still remains a great challenge. Herein, ultrafine SnS/SnO2 heterostructures were successfully fabricated and showed enhanced charge-transfer capability. The mobility enhancement is attributed to the interface effect of heterostructures, which induces an electric field within the nanocrystals, giving them much lower ion-diffusion resistance and facilitating interfacial electron transport. PMID- 26844807 TI - A Call for Consensus on Methodology and Terminology to Improve Comparability in the Study of Preventable Prehospital Trauma Deaths: A Systematic Literature Review. AB - OBJECTIVES: The study of preventable deaths is essential to trauma research for measuring service quality and highlighting avenues for improving care and as a performance indicator. However, variations in the terminology and methodology of studies on preventable prehospital trauma death limit the comparability and wider application of data. The objective of this study was to describe the heterogeneity in terminology and methodology. METHODS: We performed a systematic literature review and report this using the PRISMA guidelines. Searches were conducted using PubMed (including Medline), Ovid, and Embase databases. Studies, with a full text available in English published between 1990 and 2015, meeting the following inclusion criteria were included: analysis of 1) deaths from trauma, 2) occurring in the prehospital phase of care, and 3) application of criteria to ascertain whether deaths were preventable. One author screened database results for relevance by title and abstract. The full text of identified papers was reviewed for inclusion. The reference list of included papers was screened for studies not identified by the database search. Data were extracted on predefined core elements relating to preventability reporting and definitions using a standardized form. RESULTS: Twenty-seven studies meeting the inclusion criteria were identified: 12 studies used two categories to assess the preventability of death while 15 used three categories. Fifteen variations in the terminology of these categories and combination with death descriptors were found. Eleven different approaches were used in defining what constituted a preventable death. Twenty-one included survivability of injuries as a criterion. Methods used to determine survivability differed and eight variations in parameters for categorization of deaths were used. Nineteen used panel review in determining preventability with six implementing panel blinding. Panel composition varied greatly by expertise of personnel. Separation of prehospital deaths differed with 10 separating those dead at scene (DAS) and dead on arrival, three excluding those DAS, three excluding deaths prior to EMS arrival, and 11 not separating prehospital deaths. CONCLUSIONS: The heterogeneity in methodology, terminology, and definitions of "preventable" between studies render data incomparable. To facilitate common understanding, comparability, and analysis, a commonly agreed ontology by the prehospital research community is required. PMID- 26844808 TI - Microalgal bioengineering for sustainable energy development: Recent transgenesis and metabolic engineering strategies. AB - Exploring the efficiency of algae to produce remarkable products can be directly benefitted by studying its mechanism at systems level. Recent advents in biotechnology like flux balance analysis (FBA), genomics and in silico proteomics minimize the wet lab exertion. It is understood that FBA predicts the metabolic products, metabolic pathways and alternative pathway to maximize the desired product, and these are key components for microalgae bio-engineering. This review encompasses recent transgenesis techniques and metabolic engineering strategies applied to different microalgae for improving different traits. Further it also throws light on RNAi and riboswitch engineering based methods which may be advantageous for high throughput microalgal research. A valid and optimally designed microalga can be developed where every engineering strategies meet each other successfully and will definitely fulfill the market needs. It is also to be noted that Omics (viz. genetic and metabolic manipulation with bioinformatics) should be integrated to develop a strain which could prove to be a futuristic solution for sustainable development for energy. PMID- 26844809 TI - Lungs From the Controlled Donation After Circulatory Determination of Death Donor: Perspectives From the United States and Beyond. PMID- 26844810 TI - Pancreatic polypeptide and its central Y4 receptors are essential for cued fear extinction and permanent suppression of fear. AB - BACKGROUND AND PURPOSE: Avoiding danger and finding food are closely related behaviours that are essential for surviving in a natural environment. Growing evidence supports an important role of gut-brain peptides in modulating energy homeostasis and emotional-affective behaviour. For instance, postprandial release of pancreatic polypeptide (PP) reduced food intake and altered stress-induced motor activity and anxiety by activating central Y4 receptors. EXPERIMENTAL APPROACH: We characterized [K(30) (PEG2)]hPP2-36 as long-acting Y4 receptor agonist and injected it peripherally into wildtype and Y4 receptor knockout (Y4KO) C57Bl/6NCrl mice to investigate the role of Y4 receptors in fear conditioning. Extinction and relapse after extinction was measured by spontaneous recovery and renewal. KEY RESULTS: The Y4KO mice showed impaired cued and context fear extinction without affecting acquisition, consolidation or recall of fear. Correspondingly, peripheral injection of [K(30) (PEG2)]hPP2-36 facilitated extinction learning upon fasting, an effect that was long-lasting and generalized. Furthermore, peripherally applied [K(30) (PEG2)]hPP2-36 before extinction inhibited the activation of orexin-expressing neurons in the lateral hypothalamus in WT, but not in Y4KO mice. CONCLUSIONS AND IMPLICATIONS: Our findings suggests suppression of excessive arousal as a possible mechanism for the extinction-promoting effect of central Y4 receptors and provide strong evidence that fear extinction requires integration of vegetative stimuli with cortical and subcortical information, a process crucially depending on Y4 receptors. Importantly, in the lateral hypothalamus two peptide systems, PP and orexin, interact to generate an emotional response adapted to the current homeostatic state. Detailed investigations of feeding-relevant genes may thus deliver multiple intervention points for treating anxiety-related disorders. PMID- 26844811 TI - Inter-hemispheric connectivity in the fusiform gyrus supports memory consolidation for faces. AB - This study investigated how changes of functional connectivity over time accompany consolidation of face memories. Based on previous research, it was hypothesized that connectivity changes in networks initially active during face perception and face encoding would be associated with individual recognition memory performance. Resting-state functional connectivity was examined shortly before, shortly after and about 40 min after incidental learning of faces. Memory performance was assessed in a surprise recognition test shortly after the last resting-state session. Results reveal that memory performance-related connectivity between the left fusiform face area and other brain areas gradually changed over the course of the experiment. Specifically, the increase in connectivity with the contralateral fusiform gyrus, the hippocampus, the amygdala and the inferior frontal gyrus correlated with recognition memory performance. As the increase in connectivity in the two final resting-state sessions was associated with memory performance, the present results demonstrate that memory formation is not restricted to the incidental learning phase but continues and increases in the following 40 min. It is discussed that the delayed increase in inter-hemisphere connectivity between the left and right fusiform gyrus is an indicator for memory formation and consolidation processes. PMID- 26844812 TI - Spatial and temporal variation in microcystin occurrence in wadeable streams in the southeastern United States. AB - Despite historical observations of potential microcystin-producing cyanobacteria (including Leptolyngbya, Phormidium, Pseudoanabaena, and Anabaena species) in 74% of headwater streams in Alabama, Georgia, South Carolina, and North Carolina (USA) from 1993 to 2011, fluvial cyanotoxin occurrence has not been systematically assessed in the southeastern United States. To begin to address this data gap, a spatial reconnaissance of fluvial microcystin concentrations was conducted in 75 wadeable streams in the Piedmont region (southeastern USA) during June 2014. Microcystins were detected using enzyme-linked immunosorbent assay (limit = 0.10 ug/L) in 39% of the streams with mean, median, and maximum detected concentrations of 0.29 ug/L, 0.11 ug/L, and 3.2 ug/L, respectively. Significant (alpha = 0.05) correlations were observed between June 2014 microcystin concentrations and stream flow, total nitrogen to total phosphorus ratio, and water temperature; but each of these factors explained 38% or less of the variability in fluvial microcystins across the region. Temporal microcystin variability was assessed monthly through October 2014 in 5 of the streams where microcystins were observed in June and in 1 reference location; microcystins were repeatedly detected in all but the reference stream. Although microcystin concentrations in the present study did not exceed World Health Organization recreational guidance thresholds, their widespread occurrence demonstrates the need for further investigation of possible in-stream environmental health effects as well as potential impacts on downstream lakes and reservoirs. Environ Toxicol Chem 2016;35:2281-2287. Published 2016 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and, as such, is in the public domain in the United States of America. PMID- 26844813 TI - ssDNA-Functionalized Nanoceria: A Redox-Active Aptaswitch for Biomolecular Recognition. AB - Quantification of biomolecular binding events is a critical step for the development of biorecognition assays for diagnostics and therapeutic applications. This paper reports the design of redox-active switches based on aptamer conjugated nanoceria for detection and quantification of biomolecular recognition. It is shown that the conformational transition state of the aptamer on nanoceria, combined with the redox properties of these particles can be used to create surface based structure switchable aptasensing platforms. Changes in the redox properties at the nanoceria surface upon binding of the ssDNA and its target analyte enables rapid and highly sensitive measurement of biomolecular interactions. This concept is demonstrated as a general applicable method to the colorimetric detection of DNA binding events. An example of a nanoceria aptaswitch for the colorimetric sensing of Ochratoxin A (OTA) and applicability to other targets is provided. The system can sensitively and selectivity detect as low as 0.15 * 10(-9) m OTA. This novel assay is simple in design and does not involve oligonucleotide labeling or elaborate nanoparticle modification steps. The proposed mechanism discovered here opens up a new way of designing optical sensing methods based on aptamer recognition. This approach can be broadly applicable to many bimolecular recognition processes and related applications. PMID- 26844815 TI - Highly Sensitive and Selective Ethanol Sensor Fabricated with In-Doped 3DOM ZnO. AB - ZnO is an important n-type semiconductor sensing material. Currently, much attention has been attracted to finding an effective method to prepare ZnO nanomaterials with high sensing sensitivity and excellent selectivity. A three dimensionally ordered macroporous (3DOM) ZnO nanostructure with a large surface area is beneficial to gas and electron transfer, which can enhance the gas sensitivity of ZnO. Indium (In) doping is an effective way to improve the sensing properties of ZnO. In this paper, In-doped 3DOM ZnO with enhanced sensitivity and selectivity has been synthesized by using a colloidal crystal templating method. The 3DOM ZnO with 5 at. % of In-doping exhibits the highest sensitivity (~88) to 100 ppm ethanol at 250 degrees C, which is approximately 3 times higher than that of pure 3DOM ZnO. The huge improvement to the sensitivity to ethanol was attributed to the increase in the surface area and the electron carrier concentration. The doping by In introduces more electrons into the matrix, which is helpful for increasing the amount of adsorbed oxygen, leading to high sensitivity. The In-doped 3DOM ZnO is a promising material for a new type of ethanol sensor. PMID- 26844814 TI - Infrared A radiation promotes survival of human melanocytes carrying ultraviolet radiation-induced DNA damage. AB - The link between solar radiation and melanoma is still elusive. Although infrared radiation (IR) accounts for over 50% of terrestrial solar energy, its influence on human skin is not well explored. There is increasing evidence that IR influences the expression patterns of several molecules independently of heat. A previous in vivo study revealed that pretreatment with IR might promote the development of UVR-induced non-epithelial skin cancer and possibly of melanoma in mice. To expand on this, the aim of the present study was to evaluate the impact of IR on UVR-induced apoptosis and DNA repair in normal human epidermal melanocytes. The balance between these two effects is a key factor of malignant transformation. Human melanocytes were exposed to physiologic doses of IR and UVR. Compared to cells irradiated with UVR only, simultaneous exposure to IR significantly reduced the apoptotic rate. However, IR did not influence the repair of UVR-induced DNA damage. IR partly reversed the pro-apoptotic effects of UVR via modification of the expression and activity of proteins mainly of the extrinsic apoptotic pathway. In conclusion, IR enhances the survival of melanocytes carrying UVR-induced DNA damage and thereby might contribute to melanomagenesis. PMID- 26844816 TI - Spinal Epidural Hematoma Following Cupping Glass Treatment in an Infant With Hemophilia A. AB - A 6 months old infant, diagnosed with a rare mutation causing severe hemophilia A, presented with spinal epidural hematoma. Parents later admitted the infant had glass cupping therapy performed within 2 weeks of the onset of symptoms. The rare mutation, rare bleeding complication, and the eventual course of therapy applied in this case will be discussed in our case report. PMID- 26844817 TI - Bleb compression and autologous blood for relief of bleb dysaesthesia. Does it work? PMID- 26844819 TI - Variable selection for distribution-free models for longitudinal zero-inflated count responses. AB - Zero-inflated count outcomes arise quite often in research and practice. Parametric models such as the zero-inflated Poisson and zero-inflated negative binomial are widely used to model such responses. Like most parametric models, they are quite sensitive to departures from assumed distributions. Recently, new approaches have been proposed to provide distribution-free, or semi-parametric, alternatives. These methods extend the generalized estimating equations to provide robust inference for population mixtures defined by zero-inflated count outcomes. In this paper, we propose methods to extend smoothly clipped absolute deviation (SCAD)-based variable selection methods to these new models. Variable selection has been gaining popularity in modern clinical research studies, as determining differential treatment effects of interventions for different subgroups has become the norm, rather the exception, in the era of patent centered outcome research. Such moderation analysis in general creates many explanatory variables in regression analysis, and the advantages of SCAD-based methods over their traditional counterparts render them a great choice for addressing this important and timely issues in clinical research. We illustrate the proposed approach with both simulated and real study data. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26844820 TI - Site-Selective Intermolecular Oxidative C-3 Alkenylation of 7-Azaindoles at Room Temperature. AB - A previously unexplored palladium-catalyzed C-3 selective alkenylation of 7 azaindoles, performed in the presence of Pd(OAc)2 as the catalyst, PPh3 as the ligand, Cu(OTf)2 as an oxidative cocatalyst, and molecular oxygen (O2) as the terminal oxidant at room temperature, has been reported. This direct alkenylation strategy offers a new approach in functionalizing pharmaceutically important 7 azaindoles. PMID- 26844821 TI - Structure of Rigid Polymers Confined to Nanoparticles: Molecular Dynamics Simulations Insight. AB - Nanoparticles (NPs) grafted with organic layers form hybrids able to retain their unique properties through integration into the mesoscopic scale. The organic layer structure and response often determine the functionality of the hybrids on the mesoscopic length scale. Using molecular dynamics (MD) simulations, we probe the conformation of luminescent rigid polymers, dialkyl poly(p-phenylene ethynylene)s (PPE), end-grafted onto a silica nanoparticle in different solvents as the molecular weights and polymer coverages are varied. We find that, in contrast to NP-grafted flexible polymers, the chains are fully extended independent of the solvent. In toluene and decane, which are good solvents, the grafted PPEs chains assume a similar conformation to that observed in dilute solutions. In water, which is a poor solvent for the PPEs, the polymer chains form one large cluster but remain extended. The radial distribution of the chains around the core of the nanoparticle is homogeneous in good solvents, whereas in poor solvents clusters are formed independent of molecular weights and coverages. The clustering is distinctively different from the response of grafted flexible and semiflexible polymers. PMID- 26844818 TI - Transcript level coordination of carbon pathways during silicon starvation induced lipid accumulation in the diatom Thalassiosira pseudonana. AB - Diatoms are one of the most productive and successful photosynthetic taxa on Earth and possess attributes such as rapid growth rates and production of lipids, making them candidate sources of renewable fuels. Despite their significance, few details of the mechanisms used to regulate growth and carbon metabolism are currently known, hindering metabolic engineering approaches to enhance productivity. To characterize the transcript level component of metabolic regulation, genome-wide changes in transcript abundance were documented in the model diatom Thalassiosira pseudonana on a time-course of silicon starvation. Growth, cell cycle progression, chloroplast replication, fatty acid composition, pigmentation, and photosynthetic parameters were characterized alongside lipid accumulation. Extensive coordination of large suites of genes was observed, highlighting the existence of clusters of coregulated genes as a key feature of global gene regulation in T. pseudonana. The identity of key enzymes for carbon metabolic pathway inputs (photosynthesis) and outputs (growth and storage) reveals these clusters are organized to synchronize these processes. Coordinated transcript level responses to silicon starvation are probably driven by signals linked to cell cycle progression and shifts in photophysiology. A mechanistic understanding of how this is accomplished will aid efforts to engineer metabolism for development of algal-derived biofuels. PMID- 26844822 TI - Glucocorticoid-induced changes in glucocorticoid receptor mRNA and protein expression in the human placenta as a potential factor for altering fetal growth and development. AB - Glucocorticoids (GCs) control essential metabolic processes in virtually every cell in the body and play a vital role in the development of fetal tissues and organ systems. The biological actions of GCs are mediated via glucocorticoid receptors (GRs), the cytoplasmic transcription factors that regulate the transcription of genes involved in placental and fetal growth and development. Several experimental studies have demonstrated that fetal exposure to high maternal GC levels early in gestation is associated with adverse fetal outcomes, including low birthweight, intrauterine growth restriction and anatomical and structural abnormalities that may increase the risk of cardiovascular, metabolic and neuroendocrine disorders in adulthood. The response of the fetus to GCs is dependent on gender, with female fetuses becoming hypersensitive to changes in GC levels whereas male fetuses develop GC resistance in the environment of high maternal GCs. In this paper we review GR function and the physiological and pathological effects of GCs on fetal development. We propose that GC-induced changes in the placental structure and function, including alterations in the expression of GR mRNA and protein levels, may play role in inhibiting in utero fetal growth. PMID- 26844823 TI - Actinide-Catalyzed Intermolecular Addition of Alcohols to Carbodiimides. AB - The unprecedented actinide-catalyzed addition of alcohols to carbodiimides is presented. This represents a rare example of thorium-catalyzed transformations of an alcoholic substrate and the first example of uranium complexes showing catalytic reactivity with alcohols. Using the uranium and thorium amides U[N(SiMe3)2]3 and [(Me3Si)2N]2An[kappa(2)-(N,C)-CH2Si(CH3)2N(SiMe3)] (An = Th or U), alcohol additions to unsaturated carbon-nitrogen bonds are achieved in short reaction times with excellent selectivities and high to excellent yields. Computational studies, supported by experimental thermodynamic data, suggest plausible models of the profile of the reaction which allow the system to overcome the high barrier of scission of the actinide-oxygen bond. Accompanied by experimentally determined kinetic parameters, a plausible mechanism is proposed for the catalytic cycle. PMID- 26844824 TI - Fly Dscams Can Also Help You Find the Right Partners. AB - The modular reiterative pattern of the fly visual system makes it an ideal model to study axon guidance and synaptogenesis. In this issue of Neuron, Tadros et al. (2016) show that Dscam2/4 promote the anchoring of dendrites to their targets. PMID- 26844825 TI - Can You Hear Me Now? AB - Auditory communication is central to the social interactions of many animals. In fruit flies, males sing to court females. Coen et al. (2016) demonstrate that males can dynamically adjust the loudness of their songs according to the distance to a female. PMID- 26844826 TI - Recurrent Feedback Loops in Associative Learning. AB - In this issue of Neuron, Gao et al. (2016) report on a little-studied feedback pathway from the cerebellar nuclei back to the cerebellar cortex. They find that it contributes to associative conditioning and execution of learned movements, highlighting a role for local feedback loops in the brain. PMID- 26844827 TI - Reducing Speed and Sight: How Adaptive Is Post-Error Slowing? AB - After errors, decision boundaries change, which results in post-error slowing of decisions. Purcell and Kiani (2016) report simultaneously decreased sensitivity to sensory information counteracts post-error increases in accuracy. Early post error adjustments reflect a general orienting reflex rather than goal-directed adaptation. PMID- 26844830 TI - Dynein Regulator NDEL1 Controls Polarized Cargo Transport at the Axon Initial Segment. AB - The development and homeostasis of neurons relies heavily on the selective targeting of vesicles into axon and dendrites. Microtubule-based motor proteins play an important role in polarized transport; however, the sorting mechanism to exclude dendritic cargo from the axon is unclear. We show that the dynein regulator NDEL1 controls somatodendritic cargo transport at the axon initial segment (AIS). NDEL1 localizes to the AIS via an interaction with the scaffold protein Ankyrin-G. Depletion of NDEL1 or its binding partner LIS1 results in both cell-wide and local defects, including the non-polarized trafficking of dendritic cargo through the AIS. We propose a model in which LIS1 is a critical mediator of local NDEL1-based dynein activation at the AIS. By localizing to the AIS, NDEL1 facilitates the reversal of somatodendritic cargos in the proximal axon. PMID- 26844829 TI - Axon Self-Destruction: New Links among SARM1, MAPKs, and NAD+ Metabolism. AB - Wallerian axon degeneration is a form of programmed subcellular death that promotes axon breakdown in disease and injury. Active degeneration requires SARM1 and MAP kinases, including DLK, while the NAD+ synthetic enzyme NMNAT2 prevents degeneration. New studies reveal that these pathways cooperate in a locally mediated axon destruction program, with NAD+ metabolism playing a central role. Here, we review the biology of Wallerian-type axon degeneration and discuss the most recent findings, with special emphasis on critical signaling events and their potential as therapeutic targets for axonopathy. PMID- 26844828 TI - Prions and Protein Assemblies that Convey Biological Information in Health and Disease. AB - Prions derived from the prion protein (PrP) were first characterized as infectious agents that transmit pathology between individuals. However, the majority of cases of neurodegeneration caused by PrP prions occur sporadically. Proteins that self-assemble as cross-beta sheet amyloids are a defining pathological feature of infectious prion disorders and all major age-associated neurodegenerative diseases. In fact, multiple non-infectious proteins exhibit properties of template-driven self-assembly that are strikingly similar to PrP. Evidence suggests that like PrP, many proteins form aggregates that propagate between cells and convert cognate monomer into ordered assemblies. We now recognize that numerous proteins assemble into macromolecular complexes as part of normal physiology, some of which are self-amplifying. This review highlights similarities among infectious and non-infectious neurodegenerative diseases associated with prions, emphasizing the normal and pathogenic roles of higher order protein assemblies. We propose that studies of the structural and cellular biology of pathological versus physiological aggregates will be mutually informative. PMID- 26844831 TI - Dscam Proteins Direct Dendritic Targeting through Adhesion. AB - Cell recognition molecules are key regulators of neural circuit assembly. The Dscam family of recognition molecules in Drosophila has been shown to regulate interactions between neurons through homophilic repulsion. This is exemplified by Dscam1 and Dscam2, which together repel dendrites of lamina neurons, L1 and L2, in the visual system. By contrast, here we show that Dscam2 directs dendritic targeting of another lamina neuron, L4, through homophilic adhesion. Through live imaging and genetic mosaics to dissect interactions between specific cells, we show that Dscam2 is required in L4 and its target cells for correct dendritic targeting. In a genetic screen, we identified Dscam4 as another regulator of L4 targeting which acts with Dscam2 in the same pathway to regulate this process. This ensures tiling of the lamina neuropil through heterotypic interactions. Thus, different combinations of Dscam proteins act through distinct mechanisms in closely related neurons to pattern neural circuits. PMID- 26844832 TI - Early Somatostatin Interneuron Connectivity Mediates the Maturation of Deep Layer Cortical Circuits. AB - The precise connectivity of somatostatin and parvalbumin cortical interneurons is generated during development. An understanding of how these interneuron classes incorporate into cortical circuitry is incomplete but essential to elucidate the roles they play during maturation. Here, we report that somatostatin interneurons in infragranular layers receive dense but transient innervation from thalamocortical afferents during the first postnatal week. During this period, parvalbumin interneurons and pyramidal neurons within the same layers receive weaker thalamocortical inputs, yet are strongly innervated by somatostatin interneurons. Further, upon disruption of the early (but not late) somatostatin interneuron network, the synaptic maturation of thalamocortical inputs onto parvalbumin interneurons is perturbed. These results suggest that infragranular somatostatin interneurons exhibit a transient early synaptic connectivity that is essential for the establishment of thalamic feedforward inhibition mediated by parvalbumin interneurons. PMID- 26844833 TI - A Transient Translaminar GABAergic Interneuron Circuit Connects Thalamocortical Recipient Layers in Neonatal Somatosensory Cortex. AB - GABAergic activity is thought to influence developing neocortical sensory circuits. Yet the late postnatal maturation of local layer (L)4 circuits suggests alternate sources of GABAergic control in nascent thalamocortical networks. We show that a population of L5b, somatostatin (SST)-positive interneuron receives early thalamic synaptic input and, using laser-scanning photostimulation, identify an early transient circuit between these cells and L4 spiny stellates (SSNs) that disappears by the end of the L4 critical period. Sensory perturbation disrupts the transition to a local GABAergic circuit, suggesting a link between translaminar and local control of SSNs. Conditional silencing of SST+ interneurons or conversely biasing the circuit toward local inhibition by overexpression of neuregulin-1 type 1 results in an absence of early L5b GABAergic input in mutants and delayed thalamic innervation of SSNs. These data identify a role for L5b SST+ interneurons in the control of SSNs in the early postnatal neocortex. PMID- 26844834 TI - Bidirectional Synaptic Structural Plasticity after Chronic Cocaine Administration Occurs through Rap1 Small GTPase Signaling. AB - Dendritic spines are the sites of most excitatory synapses in the CNS, and opposing alterations in the synaptic structure of medium spiny neurons (MSNs) of the nucleus accumbens (NAc), a primary brain reward region, are seen at early versus late time points after cocaine administration. Here we investigate the time-dependent molecular and biochemical processes that regulate this bidirectional synaptic structural plasticity of NAc MSNs and associated changes in cocaine reward in response to chronic cocaine exposure. Our findings reveal key roles for the bidirectional synaptic expression of the Rap1b small GTPase and an associated local synaptic protein translation network in this process. The transcriptional mechanisms and pathway-specific inputs to NAc that regulate Rap1b expression are also characterized. Collectively, these findings provide a precise mechanism by which nuclear to synaptic interactions induce "metaplasticity" in NAc MSNs, and we reveal the specific effects of this plasticity on reward behavior in a brain circuit-specific manner. PMID- 26844835 TI - Sensorimotor Transformations Underlying Variability in Song Intensity during Drosophila Courtship. AB - Diverse animal species, from insects to humans, utilize acoustic signals for communication. Studies of the neural basis for song or speech production have focused almost exclusively on the generation of spectral and temporal patterns, but animals can also adjust acoustic signal intensity when communicating. For example, humans naturally regulate the loudness of speech in accord with a visual estimate of receiver distance. The underlying mechanisms for this ability remain uncharacterized in any system. Here, we show that Drosophila males modulate courtship song amplitude with female distance, and we investigate each stage of the sensorimotor transformation underlying this behavior, from the detection of particular visual stimulus features and the timescales of sensory processing to the modulation of neural and muscle activity that generates song. Our results demonstrate an unanticipated level of control in insect acoustic communication and uncover novel computations and mechanisms underlying the regulation of acoustic signal intensity. PMID- 26844836 TI - Excitatory Cerebellar Nucleocortical Circuit Provides Internal Amplification during Associative Conditioning. AB - Closed-loop circuitries between cortical and subcortical regions can facilitate precision of output patterns, but the role of such networks in the cerebellum remains to be elucidated. Here, we characterize the role of internal feedback from the cerebellar nuclei to the cerebellar cortex in classical eyeblink conditioning. We find that excitatory output neurons in the interposed nucleus provide efference-copy signals via mossy fibers to the cerebellar cortical zones that belong to the same module, triggering monosynaptic responses in granule and Golgi cells and indirectly inhibiting Purkinje cells. Upon conditioning, the local density of nucleocortical mossy fiber terminals significantly increases. Optogenetic activation and inhibition of nucleocortical fibers in conditioned animals increases and decreases the amplitude of learned eyeblink responses, respectively. Our data show that the excitatory nucleocortical closed-loop circuitry of the cerebellum relays a corollary discharge of premotor signals and suggests an amplifying role of this circuitry in controlling associative motor learning. PMID- 26844838 TI - Antineoplastic Effects of PPARgamma Agonists, with a Special Focus on Thyroid Cancer. AB - Peroxisome Proliferator-Activated Receptor-gamma (PPARgamma) is a ligand activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARgamma is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARgamma in tumor development and/or progression. PPARgamma is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARgamma agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARgamma that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARgamma agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re activating blocked terminal differentiation programs. PPARgamma agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARgamma agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients. PMID- 26844837 TI - Kartogenin-Incorporated Thermogel Supports Stem Cells for Significant Cartilage Regeneration. AB - Recently, cartilage tissue engineering (CTE) attracts increasing attention in cartilage defect repair. In this work, kartogenin (KGN), an emerging chondroinductive nonprotein small molecule, was incorporated into a thermogel of poly(L-lactide-co-glycolide)-poly(ethylene glycol)-poly(L-lactide-co-glycolide) (PLGA-PEG-PLGA) to fabricate an appropriate microenvironment of bone marrow mesenchymal stem cells (BMSCs) for effective cartilage regeneration. More integrative and smoother repaired articular surface, more abundant characteristic glycosaminoglycans (GAGs) and collagen II (COL II), and less degeneration of normal cartilage were obtained in the KGN and BMSCs coloaded thermogel group in vivo. In conclusion, the KGN-loaded PLGA-PEG-PLGA thermogel can be utilized as an alternative support for BMSCs to regenerate damaged cartilage in vivo. PMID- 26844839 TI - Long-Term Teduglutide for the Treatment of Patients With Intestinal Failure Associated With Short Bowel Syndrome. AB - OBJECTIVES: In the pivotal 24-week, phase III, placebo-controlled trial, teduglutide significantly reduced parenteral support (PS) requirements in patients with short bowel syndrome (SBS). STEPS-2 was a 2-year, open-label extension of that study designed to evaluate long-term safety and efficacy of teduglutide. METHODS: Enrolled patients had completed 24 weeks of either teduglutide (TED/TED) or placebo (PBO/TED) in the initial placebo-controlled study or qualified for that study, but were not treated (NT/TED) because of full enrollment. Patients received subcutaneous teduglutide 0.05 mg/kg/day for up to 24 months (NT/TED and PBO/TED) or up to 30 months (TED/TED). Clinical response was defined as 20-100% reduction from baseline in weekly PS volume; baseline was considered the beginning of teduglutide treatment in the initial placebo controlled study (TED/TED) or STEPS-2 (NT/TED and PBO/TED). Descriptive statistics summarized changes in efficacy and safety variables. RESULTS: Of 88 enrolled patients, 65 (74%) completed STEPS-2. The most common treatment-emergent adverse events were abdominal pain (34%), catheter sepsis (28%), and decreased weight (25%). Mean weight, body mass index, and serum albumin remained stable. In patients who completed the study, clinical response was achieved in 28/30 (93%) TED/TED, 16/29 (55%) PBO/TED, and 4/6 (67%) NT/TED patients. Mean PS volume reductions from baseline were 7.6 (66%), 3.1 (28%), and 4.0 (39%) l/week in the TED/TED, PBO/TED, and NT/TED groups, respectively. Thirteen patients achieved full enteral autonomy. CONCLUSIONS: In patients with SBS, long-term teduglutide treatment resulted in sustained, continued reductions in PS requirements. Overall health and nutritional status was maintained despite PS reductions. PMID- 26844840 TI - A Randomized Trial Comparing Skin Antiseptic Agents at Cesarean Delivery. AB - BACKGROUND: Preoperative skin antisepsis has the potential to decrease the risk of surgical-site infection. However, evidence is limited to guide the choice of antiseptic agent at cesarean delivery, which is the most common major surgical procedure among women in the United States. METHODS: In this single-center, randomized, controlled trial, we evaluated whether the use of chlorhexidine alcohol for preoperative skin antisepsis was superior to the use of iodine alcohol for the prevention of surgical-site infection after cesarean delivery. We randomly assigned patients undergoing cesarean delivery to skin preparation with either chlorhexidine-alcohol or iodine-alcohol. The primary outcome was superficial or deep surgical-site infection within 30 days after cesarean delivery, on the basis of definitions from the Centers for Disease Control and Prevention. RESULTS: From September 2011 through June 2015, a total of 1147 patients were enrolled; 572 patients were assigned to chlorhexidine-alcohol and 575 to iodine-alcohol. In an intention-to-treat analysis, surgical-site infection was diagnosed in 23 patients (4.0%) in the chlorhexidine-alcohol group and in 42 (7.3%) in the iodine-alcohol group (relative risk, 0.55; 95% confidence interval, 0.34 to 0.90; P=0.02). The rate of superficial surgical-site infection was 3.0% in the chlorhexidine-alcohol group and 4.9% in the iodine-alcohol group (P=0.10); the rate of deep infection was 1.0% and 2.4%, respectively (P=0.07). The frequency of adverse skin reactions was similar in the two groups. CONCLUSIONS: The use of chlorhexidine-alcohol for preoperative skin antisepsis resulted in a significantly lower risk of surgical-site infection after cesarean delivery than did the use of iodine-alcohol. (Funded by the National Institutes of Health and Washington University School of Medicine in St. Louis; ClinicalTrials.gov number, NCT01472549.). PMID- 26844842 TI - The origin of grain boundary capacitance in highly doped ceria. AB - The origin of a grain-boundary capacitance in mixed oxide-ion/electronic conductors has been investigated for the case of Ce0.8Sm0.2O1.9-delta using a.c. impedance spectroscopy under low pO2 from 250 to 400 degrees C. The observed capacitance is interpreted in terms of Ce(III):4f(1) electrons first introduced into the grains and not into the grain boundaries. PMID- 26844845 TI - Anger and depression levels of mothers with premature infants in the neonatal intensive care unit. AB - BACKGROUND: The aim of this study was to examine anger and depression levels of mothers who had a premature infant in the NICU, and all factors affecting the situation. METHODS: This descriptive study was performed in the level I and II units of NICU at three state hospitals in Turkey. The data was collected with a demographic questionnaire, "Beck Depression Inventory" and "Anger Expression Scale". Descriptive statistics, parametric and nonparametric statistical tests and Pearson correlation were used in the data analysis. RESULTS: Mothers whose infants are under care in NICU have moderate depression. It has also been determined that mothers' educational level, income level and gender of infants were statistically significant (p <0.05). A positive relationship between depression and trait anger scores was found to be statistically significant. A negative relationship existed between depression and anger-control scores for the mothers, which was statistically significant (p <0.05). CONCLUSIONS: Due to the results of research, recommended that mothers who are at risk of depression and anger in the NICU evaluated by nurses and these nurses to develop their consulting roles. PMID- 26844844 TI - Non-invasive spectroscopy of transfusable red blood cells stored inside sealed plastic blood-bags. AB - After being separated from (donated) whole blood, red blood cells are suspended in specially formulated additive solutions and stored (at 4 degrees C) in polyvinyl chloride (PVC) blood-bags until they are needed for transfusion. With time, the prepared red cell concentrate (RCC) is known to undergo biochemical changes that lower effectiveness of the transfusion, and thus regulations are in place that limit the storage period to 42 days. At present, RCC is not subjected to analytical testing prior to transfusion. In this study, we use Spatially Offset Raman Spectroscopy (SORS) to probe, non-invasively, the biochemistry of RCC inside sealed blood-bags. The retrieved spectra compare well with conventional Raman spectra (of sampled aliquots) and are dominated by features associated with hemoglobin. In addition to the analytical demonstration that SORS can be used to retrieve RCC spectra from standard clinical blood-bags without breaking the sterility of the system, the data reveal interesting detail about the oxygenation-state of the stored cells themselves, namely that some blood-bags unexpectedly contain measurable amounts of deoxygenated hemoglobin after weeks of storage. The demonstration that chemical information can be obtained non invasively using spectroscopy will enable new studies of RCC degeneration, and points the way to a Raman-based instrument for quality-control in a blood-bank or hospital setting. PMID- 26844843 TI - Prevalence of Malignancies in Patients With Primary Aldosteronism. AB - CONTEXT: Primary aldosteronism (PA) is the most common cause of secondary hypertension. Aldosterone excess can cause DNA damage in vitro and in vivo. Single case reports have indicated a coincidence of PA with renal cell carcinoma and other tumors. However, the prevalence of benign and malignant neoplasms in patients with PA has not yet been studied. PATIENTS AND DESIGN: In the multicenter MEPHISTO study, the prevalence of benign and malignant tumors was investigated in 335 patients with confirmed PA. Matched hypertensive subjects from the population-based Study of Health in Pomerania cohort served as controls. RESULTS: Of the 335 PA patients, 119 (35.5%) had been diagnosed with a tumor at any time, and 30 had two or more neoplasms. Lifetime malignancy occurrence was reported in 9.6% of PA patients compared to 6.0% of hypertensive controls (P = .08). PA patients with a history of malignancy had higher baseline aldosterone levels at diagnosis of PA (P = .009), and a strong association between aldosterone levels and the prevalence of malignancies was observed (P = .03). In total, 157 neoplasms were identified in the PA patients; they were benign in 61% and malignant in 25% of the cases (14% of unknown dignity). Renal cell carcinoma was diagnosed in five patients (13% of all malignancies) and was not reported in controls CONCLUSION: Compared to hypertensive controls, the prevalence of malignancies was positively correlated with aldosterone levels, tended to be higher in PA patients, but did not differ significantly. PMID- 26844846 TI - Prediction of Recurrence and Mortality of Locally Advanced Esophageal Cancer Patients Using Pretreatment F-18 FDG PET/CT Parameters: Intratumoral Heterogeneity, SUV, and Volumetric Parameters. AB - OBJECTIVE: This study was aimed to define the predictive values of preoperative Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (F-18 FDG PET/CT) parameters and compared to define effective parameters for prediction of overall survival (OS) and recurrent free survival (RFS) in locally advanced esophageal cancer (LAEC). MATERIALS AND METHODS: This study included 44 patients with LAEC who received F-18 FDG PET/CT. Univariate and multivariate analyses were used to calculate survival, and the survival curves were estimated by clinical factors and F-18 FDG PET/CT-derived parameters. RESULTS: Higher values of F-18 FDG PET/CT parameters (SUVmax, SUVmean, metabolic tumor volume [MTV], total lesion glycolysis [TLG]) and advanced tumor-node-metastasis (TNM) staging showed higher mortality. The Cox proportional hazard regression model demonstrated advanced TNM stage and high MTV as poor OS factors. The early TNM stage, lower MTV, lower TLG, lymph node (LN) (-), and lower heterogeneity factor (HF) were also associated with better RFS. The MTV was the potent predictor for RFS. CONCLUSIONS: In conclusion, although the newly described parameter of HF measured by F-18 FDG PET/CT could be a prognostic factor, the MTV is the most potent prognostic predictor in LAEC. PMID- 26844847 TI - Tectonic 1 Is a Key Regulator of Cell Proliferation in Pancreatic Cancer. AB - Pancreatic cancer is notoriously becoming one of the most devastating human cancers leading to death. However, clinical challenges still remain in diagnosis and treatment of this ticklish cancer. In the present study, the authors identified a new gene, Tectonic 1 (TCTN1), as a key regulator of cell proliferation in pancreatic cancer. Lentivirus-mediated short hairpin RNA (shRNA) was employed to knock down endogenous TCTN1 expression in PANC-1 pancreatic cancer cells. Knockdown of TCTN1 expression potently inhibited cell viability and proliferation, as determined by MTT and colony formation assays. Western blotting analysis also showed that knockdown of TCTN1 suppressed the expression of cdc2, while it induced that of p21 and p27. Flow cytometry analysis showed that depletion of TCTN1 in PANC-1 cells led to cell cycle arrest in the G2/M phase as well as apoptosis. Besides, depletion of TCTN1 led to the increase of Bax and cleavage of PARP-1, but the decrease of bcl2 by western blotting. The data indicate that TCTN1 is indispensable for pancreatic cancer cell proliferation, which provides a novel alternative to targeted therapy of pancreatic cancer and deserves further investigation. PMID- 26844848 TI - In Vitro/In Vivo Evaluation of Radiolabeled [(99m)Tc(CO)3](+)-Hydroxyurea and Fluorescein Isothiocyanate-Hydroxyurea. AB - The aim of current study is to examine hydroxyurea (HU), which is an antineoplastic drug used for the treatment of leukemia, sickle-cell disease, HIV, psoriasis, thrombocythemia, and various neoplastic diseases in two aspects. The active ingredient hydroxyurea was obtained by purification of the capsule form drug, commercially named as HYDREA. Then, [(99m)Tc(CO)3](+)core radiolabeling with HU was performed as first aspect. Quality control studies of (99m)Tc(CO)3-HU complex were performed by thin-layer radiochromatography and high-performance liquid radiochromatography methods. The results demonstrated that the radiolabeling yield was quite high (98.43% +/- 2.29%). Also, (99m)Tc(CO)3-HU complex has good stability during the 24-hour period. Biological behavior of (99m)Tc(CO)3-HU complex is evaluated by biodistribution studies on Wistar Albino rats. Fluorescein isothiocyanate (FITC) labeling of HU was performed as second aspect. Fluorometric evaluation of binding efficacy and fluorescence imaging studies on MCF7 and Hela cell lines were carried out. It was thought that the knowledge achieved in this study would contribute to using (99m)Tc(CO)3-HU complex as an imaging agent, which inhibits the DNA synthesis selectively, by inhibiting ribonucleotide reductase enzyme. It was observed that FITC-HU has noteworthy incorporation on both cell lines. PMID- 26844849 TI - Improving the In Vivo Profile of Minigastrin Radiotracers: A Comparative Study Involving the Neutral Endopeptidase Inhibitor Phosphoramidon. AB - Minigastrin radiotracers, such as [(111)In-DOTA]MG0 ([(111)In-DOTA DGlu(1)]minigastrin), have been considered for diagnostic imaging and radionuclide therapy of CCK2R-positive human tumors, such as medullary thyroid carcinoma. However, the high kidney retention assigned to the pentaGlu(2-6) repeat in the peptide sequence has compromised their clinical applicability. On the other hand, truncated des(Glu)(2-6)-analogs, such as [(111)In-DOTA]MG11 ([(111)In-DOTA-DGlu(10),desGlu(2-6)]minigastrin), despite their low renal uptake, show poor bioavailability and tumor targeting. [(111)In]CP04 ([(111)In-DOTA DGlu(1-6)]minigastrin) acquired by Glu(2-6)/DGlu(2-6) substitution showed promising tumor-to-kidney ratios in rodents. In the present study, we compare the biological profiles of [(111)In]CP04, [(111)In-DOTA]MG11, and [(111)In-DOTA]MG0 during in situ neutral endopeptidase (NEP) inhibition, recently shown to improve the bioavailability of several peptide radiotracers. After coinjection of the NEP inhibitor, phosphoramidon (PA), the stability of [(111)In]CP04 and [(111)In DOTA]MG0 in peripheral mouse blood increased, with an exceptional >14-fold improvement monitored for [(111)In-DOTA]MG11. In line with these findings, PA treatment increased the uptake of [(111)In]CP04 (8.5 +/- 0.4%ID/g to 16.0 +/- 2.3%ID/g) and [(111)In-DOTA]MG0 (11.9 +/- 2.2%ID/g to 17.2 +/- 0.9%ID/g) in A431 CCK2R(+) tumors at 4 hours postinjection, whereas the respective increase for [(111)In-DOTA]MG11 was >6-fold (2.5 +/- 0.9%ID/g to 15.1 +/- 1.7%ID/g). Interestingly, kidney uptake remained lowest for [(111)In-DOTA]MG11, but unfavorably increased by PA treatment for [(111)In-DOTA]MG0. Thus, overall, the most favorable in vivo profile was displayed by [(111)In-DOTA]MG11 during NEP inhibition, highlighting the need to validate this promising concept in the clinic. PMID- 26844851 TI - [Bilateral Ischiofemoral Impingement: A Case Report]. AB - Ischiofemoral impingement (IFI) is a rare cause of hip pain and was first described in 1977. While it can be related to trauma, it may also be idiopathic. We report a case of IFI in a 22-year old female, who was successfully treated by resection of the lesser trochanter. However, 8 months later, symptoms recurred on the contralateral side. Surgical intervention was required to alleviate the patient's symptoms. This case report discusses the clinical, diagnostic and therapeutic features of IFI. PMID- 26844850 TI - Evaluation of a PACAP Peptide Analogue Labeled with (68)Ga Using Two Different Chelating Agents. AB - OBJECTIVE: The authors have conjugated chelating agents (DOTA and NODAGA) with a peptide (pituitary adenylate cyclase-activating peptide [PACAP] analogue) that has a high affinity for VPAC1 receptors expressed on cancer cells. To determine a suitable chelating agent for labeling with (68)Ga, they have compared the labeling kinetics and stability of these peptide conjugates. METHODS: For labeling, (68)GaCl3 was eluted in 0.1 M HCl from a [(68)Ge-(68)Ga] generator. The influences of peptide concentration, pH, and temperature on the radiolabeling efficiency were studied. The stability was evaluated in saline, human serum, DTPA, transferrin, and metallic ions (FeCl3, CaCl2, and ZnCl2). Cell binding assay was performed using human breast cancer cells (T47D). Tissue biodistribution was studied in normal athymic nude mice. RESULTS: Optimal radiolabeling (>95.0%) of the DOTA-peptide conjugates required a higher (50 degrees C-90 degrees C) temperature and 10 minutes of incubation at pH 2-5. The NODAGA-peptide conjugate needed incubation only at 25 degrees C for 10 minutes. Both radiocomplexes were stable in saline, serum, as well as against transchelation and transmetallation. Cell binding at 37 degrees C for 15 minutes of incubation with (68)Ga-NODAGA-peptide was 34.0% compared to 24.5% for (68)Ga DOTA-peptide. Tissue biodistribution at 1 hour postinjection of both (68)Ga labeled peptide conjugates showed clearance through the kidneys. CONCLUSIONS: NODAGA-peptide showed more convenient radiolabeling features than that of DOTA peptide. PMID- 26844853 TI - [Possible Instrument Contamination in the Operating Room During Implantation of Knee and Hip Arthroplasty]. AB - Integrated ventilation systems with low turbulence displacement flow (TAV) are generally legally required in the architectural structure of operating theatres. However, it seems that the instruments laid out on sterile covered tables do not have the best possible protection from bacteria. Within an operating theatre, different bacteria counts are possible on the instruments. This prospective controlled study was conducted to demonstrate the influence of instrument tables with integrated horizontal flow on contamination with pathogens in comparison with conventional tables. In an operating theatre (OT) with a ceiling legally appropriate for TAV (2.40 m * 1.20 m), microbiological samples were placed on a table with integrated TAV flow (n = 100) and on a conventional instrument table (n = 100). The routine qualification of the OT was on an ongoing basis and was in accordance with DIN 1946-4: 1999 standards (in accordance with DIN measurement of recovery time 1946-4: 12-2008). This corresponds to the OT of the room class Ib. The results show significant differences between the two tables. The bacteria count and the percentage of contamination were many times higher on the conventional table. It is important to understand that the instruments are not completely protected against contamination after opening the pack and during the operation. Remedial measures are possible to optimise the sterility the instrument table. PMID- 26844852 TI - [Effects of Surgically Treated Pelvic Ring and Acetabular Fractures on Postural Control]. AB - BACKGROUND: The aim of surgical treatment of pelvic ring and acetabular fractures is to allow rapid mobilisation of patients in order to restore stance and gait stability (postural control), as this significantly correlates with a positive outcome. The regulation of postural stability is mainly controlled by transmission of proprioceptive stimuli. In addition, the pelvis serves as a connection between the legs and the spine and thus is also of great importance for mechanical stabilisation. It remains unclear whether surgical treatment of pelvic ring and acetabular fractures affects the regulation of postural control. Therefore, the aim of this study was to examine the impact of surgically treated pelvic ring and acetabular fractures on postural stability by means of computerised dynamic posturography (CDP) after a mean of 35 months and to compare the results with a healthy control group. PATIENTS AND METHODS: A retrospective case control study of 38 patients with surgically treated pelvic ring and acetabular fractures and 38 healthy volunteers was carried out using CDP. The average time of follow-up was 35 (12-78) months. The most important outcome parameter in this investigation was the overall stability index (OSI). Hip joint mobility, the health-related quality of life (SF-12) and pain were supplementary outcome parameters. RESULTS: It was found that surgically treated pelvic ring and acetabular fractures had no influence on postural stability. The OSI was 2.1 degrees in the patient group and 1.9 degrees in the control group. There was no significant difference between the groups in hip joint mobility. A total of 52 % of patients showed no or only mild pain. Mean health-related quality of life was the same as in the total population. CONCLUSION: Surgically treated pelvic ring and acetabular fractures do not lead to deterioration in postural control in the mid term. This is of high prognostic importance for rapid mobilisation of the patients. Therefore no increase in the risk of falling is expected after successfully treatment of fractures. PMID- 26844854 TI - [Osteoporosis: Diagnostics and Therapy According to the German Guidelines]. AB - The S3 guideline on the diagnosis and therapy of osteoporosis has existed since 2003. This was last updated in 2014. The aim of the present article is to present the knowledge needed for the diagnosis and therapy in men aged 60 or more and in postmenopausal women. The contexts of the updated guideline 1 are presented, together with comments on recent literature that has appeared since the last version. Both abbreviated and long versions of the guideline are available in the Internet under "www.dv-osteologie.org". PMID- 26844855 TI - [Negative Pressure Wound Therapy with Instillation in the Treatment of Critical Wounds]. AB - BACKGROUND: In recent decades, negative pressure wound therapy (NPWT) has become the gold standard in the treatment of infected wounds. Negative pressure wound therapy with instillation (NPWTi) is a new development, that combines conventional NPWT with instillation of fluids. OBJECTIVES: The purpose of this study was to review the results of current literature on the clinical use of NPWTi in acute and chronic wounds. MATERIAL AND METHODS: A literature search was performed using Pubmed and the Cochrane Library, including articles in English and German. RESULTS: The data suggest that NPWTi is a promising therapeutic option in the treatment of wounds, and applicable in various fields. CONCLUSIONS: NPWTi appears to be a useful adjunct in the treatment of critical wounds. However, data from prospective randomised trials to support the validity of the results are sparse. PMID- 26844856 TI - [Long-term Application of Opioids for Non-Tumor Associated Pain--Impact of the S3 Guidelines for the Field of Orthopaedic Surgery and Trauma Surgery]. AB - BACKGROUND: The S3 guidelines for long-term application of opioids for non-tumour associated pain, the so-called "LONTS", have recently been updated. German health insurance data indicated that over the last 3 to 4 years an increasing number of patients have been treated with opioids for non-tumour-associated pain. Many patients with somatoform pain disorder were treated with opioids. The S3 guidelines have therefore been modified after 5 years on the basis of a systematic literature search. METHODS: Seventeen experts in the field were appointed. In addition, among 25 medical societies, one psychological society, two patient support groups, and the DGOOC and IGOST were involved in the decision making process. RESULTS: According to the updated S3 guidelines "LONTS", opioids are a valuable treatment option in the field of orthopaedics and trauma surgery for patients suffering from chronic arthritis or back pain. One third of the patients suffering from chronic arthritis or knee pain benefit from long-term application (< 26 weeks) and show pain relief, as well as improved range of motion without severe drug-induced side effects. Patients suffering from fibromyalgia syndrome benefited from treatment with tramadol, but no other opioid is recommended for fibromyalgia. Opioids are contraindicated in primary headaches, as well as in functional and psychological disorders with pain as the leading symptom. Treatment with opioids is associated with considerable risks, among them substance abuse, sexual dysfunction and an increased mortality rate. Supportive measures, such as physical therapy, physiotherapy and/or psychotherapy, are always recommended. DISCUSSION: Opioid analgetics are a treatment option for particular pain syndromes (arthritis, back pain). However, the latest S3 guidelines emphasise patient education and therapy. The indication, effects, side effects and therapeutic objectives should be regularly assessed, both before and during treatment. Once therapeutic goals have been achieved, measures such as physical therapy, physiotherapy or psychotherapy should be continued, whereas opioid dosage should be gradually reduced. PMID- 26844857 TI - Biochip-based study of unidirectional mitochondrial transfer from stem cells to myocytes via tunneling nanotubes. AB - Tunneling nanotubes (TNTs) are small membranous tubes of 50-1000 nm diameter observed to connect cells in culture. Transfer of subcellular organelles through TNTs was observed in vitro and in vivo, but the formation and significance of these structures is not well understood. A polydimethylsiloxane biochip-based coculture model was devised to constrain TNT orientation and explore both TNT formation and TNT-mediated mitochondrial transfer. Two parallel microfluidic channels connected by an array of smaller microchannels enabled localization of stem cell and cardiomyocyte populations while allowing connections to form between them. Stem cells and cardiomyocytes were deposited in their respective microfluidic channels, and stem cell-cardiomyocyte pairs were formed via the microchannels. Formation of TNTs and transfer of stained mitochondria through TNTs was observed by 24 h real-time video recording. The data show that stem cells are 7.7 times more likely to initiate contact by initial extension of filopodia. By 24 h, 67% of nanotube connections through the microchannels are composed of cardiomyocyte membrane. Filopodial extension and retraction by stem cells draws an extension of TNTs from cardiomyocytes. MitoTracker staining shows that unidirectional transfer of mitochondria between stem cell-cardiomyocyte pairs invariably originates from stem cells. Control experiments with cardiac fibroblasts and cardiomyocytes show little nanotube formation between homotypic or mixed cell pairs and no mitochondrial transfer. These data identify a novel biological process, unidirectional mitochondrial transfer, mediated by heterotypic TNT connections. This suggests that the enhancement of cardiomyocyte function seen after stem-cell injection may be due to a bioenergetic stimulus provided by mitochondrial transfer. PMID- 26844859 TI - A Celebration of Gastro 2015: AGW-WGO International Congress! Save the Date: Gastro 2016 Abu Dhabi! PMID- 26844858 TI - The Influence of Gastric Cancer Screening on the Stage at Diagnosis and Survival: A Meta-Analysis of Comparative Studies in the Far East. AB - Gastric cancer is the fifth most common cancer and the second most common cause of cancer-related death worldwide. The aim of this review was to evaluate the effect of gastric cancer screening on the stage at diagnosis and survival from disease. A systematic review of the literature between January 1995 and December 2014 was performed. Studies that compared screened versus nonscreened populations for the diagnosis of gastric cancer and included the stage at diagnosis were analyzed. The QUADAS-2 and the ROBANS tools were used to assess the quality of the studies. A total of 11 studies from the Far East comprising 4039 participants in the screened and 6635 in the nonscreened groups were included. Screening was associated with a significant increase in the detection of early gastric cancer (EGC) [pooled odds ratio (POR)=3.90; 95% confidence interval (CI), 3.01-5.06; P<0.0001] and reduction in the incidence of advanced gastric cancer (POR=0.27; 95% CI, 0.20-0.35; P<0.0001). Furthermore, screening improved the 5-year survival significantly (hazard ratio=0.56; 95% CI, 0.48-0.66; P<0.0001). About 73% of the screened patients were found to have EGC compared with 43% of the nonscreened patients. About 8% of the screened patients were found to have advanced gastric cancer compared with 54% of the nonscreened patients. Screening for gastric cancer is useful in detecting asymptomatic patients with EGC in high-prevalence areas. This in turn increases the number of treatable cancers and improves the 5 year survival. There is a need for the development and the validation of alternative risk-stratification tools in low-incidence areas to allow for similar benefits. PMID- 26844860 TI - Current controversies in traditional and expanded carrier screening. AB - PURPOSE OF REVIEW: Expanded carrier screening, which detects carriers for a large number of autosomal recessive and X-linked diseases, is increasing in clinical utilization. A recent joint statement from multiple professional societies, in addition to a growing literature base, offers perspective on rationale, decision points, and reasonable methods of implementation. RECENT FINDINGS: Current literature addresses three areas: pre- and posttest education, including optimal use of formal genetic counseling, and differing characteristics of laboratory tests. Surveys of obstetricians and genetics providers also offer insight into optimal practice methods. SUMMARY: We review the carrier screening process in chronological sequence - pretest, test selection, and posttest results disclosure - and points to be considered, recommending possible practice protocols based on available literature and our combined laboratory and clinical practice experience. PMID- 26844861 TI - Effects of Coenzyme Q10 Supplementation on Exercise Performance and Markers of Oxidative Stress in Hemodialysis Patients: A Double-Blind Placebo-Controlled Crossover Trial. AB - Coenzyme Q10 (CoQ10) supplementation has been shown to decrease oxidative stress in a number of clinical settings. However, there are mixed results regarding the role of CoQ10 supplementation on exercise performance. Chronic kidney disease is recognized as an inflammatory state, and hemodialysis patients have low level of exercise performance. We aimed to evaluate the effect of CoQ10 supplementation on oxidative stress markers and exercise performance measures. This was a prospective, double-blind, placebo-controlled, crossover study in which all patients received placebo and oral CoQ10 200 mg/d. Participants underwent 6 minute walking test and cycle ergometer. Blood samples were drawn to determine malondialdehyde, oxidized low-density lipoprotein, superoxide dismutase, and glutathione peroxidase. Walking distance in 6-minute walking test and estimated maximal oxygen consumption (VO2max) were recorded. Twenty-eight patients were randomized, but 23 patients completed the study protocol. Serum CoQ10 level significantly increased with supplementation compared with basal values (P < 0.05). Neither walking distance nor estimated VO2max was different between the placebo and CoQ10 groups (P > 0.05). Serum malondialdehyde levels significantly increased in both groups compared with baseline values just after the exercise (P < 0.05). There was no difference in markers of oxidative stress and antioxidant system between placebo and CoQ10 supplementation with exercise (P > 0.05). The results of this study showed no significant effect of CoQ10 supplementation on exercise performance measures and oxidative system markers compared with placebo in maintenance hemodialysis patients. PMID- 26844862 TI - Robots Learn to Recognize Individuals from Imitative Encounters with People and Avatars. AB - Prior to language, human infants are prolific imitators. Developmental science grounds infant imitation in the neural coding of actions, and highlights the use of imitation for learning from and about people. Here, we used computational modeling and a robot implementation to explore the functional value of action imitation. We report 3 experiments using a mutual imitation task between robots, adults, typically developing children, and children with Autism Spectrum Disorder. We show that a particular learning architecture--specifically one combining artificial neural nets for (i) extraction of visual features, (ii) the robot's motor internal state, (iii) posture recognition, and (iv) novelty detection--is able to learn from an interactive experience involving mutual imitation. This mutual imitation experience allowed the robot to recognize the interactive agent in a subsequent encounter. These experiments using robots as tools for modeling human cognitive development, based on developmental theory, confirm the promise of developmental robotics. Additionally, findings illustrate how person recognition may emerge through imitative experience, intercorporeal mapping, and statistical learning. PMID- 26844863 TI - Airway management and training in obstetric anaesthesia. AB - PURPOSE OF REVIEW: Airway management and failed intubation in the pregnant woman requires unique considerations, which differ from the nonpregnant patient. Factors that influence airway management in this setting include anatomical and physiological changes in pregnancy, environmental factors as well as training matters. In addition, surgery is often being performed with extreme urgency, which requires rapid decision-making process that takes into account safe outcome of mother and baby. The purpose of this review is to focus on recent developments that address these exceptional airway challenges in obstetrics. RECENT FINDINGS: The first national UK obstetric difficult airway guidelines that have been recently published, are based around algorithms that deal with induction of general anaesthesia, failed intubation and front-of-the-neck access. As well as emphasising good practice in planning, preparation, and rapid sequence induction (RSI) technique, they outline how to make a provisional plan prior to the induction of general anaesthesia, on whether to awaken or continue general anaesthesia, should failed intubation occur. Current recommendations aim to move away from the traditional and outdated obstetric RSI technique to introduce changes, which are in keeping with anaesthetic practice in the nonpregnant patients. Such changes include the choice of induction agent and muscle relaxant, preoxygenation techniques, and mask ventilation during RSI; and the early release of cricoid pressure should failed intubation occur. SUMMARY: Recent advances and recommendations in the management of the obstetric airway should help to bring consistency of clinical practice, reduce adverse events, and standardize teaching by providing a structure for teaching and training on failed tracheal intubation in obstetrics. Opportunities during elective caesarean sections and simulation should be used as teaching tools to improve anaesthetists' and team performance during a crisis. PMID- 26844864 TI - Perioperative bleeding management in pediatric patients. AB - PURPOSE OF REVIEW: Managing the bleeding pediatric patient perioperatively can be extremely challenging. The primary goals include avoiding hypotension, maintaining adequate tissue perfusion and oxygenation, and maintaining hemostasis. Traditional bleeding management has consisted of transfusion of autologous blood products, however, there is strong evidence that transfusion related side-effects are associated with increased morbidity and mortality in children. Especially concerning is the increased reported incidence of noninfectious adverse events such as transfusion-related acute lung injury, transfusion-related circulatory overload and transfusion-related immunomodulation. The current approach in perioperative bleeding management of the pediatric patient should focus on the diagnosis and treatment of anemia and coagulopathy with the transfusion of blood products only when clinically indicated and guided by goal-directed strategies. RECENT FINDINGS: Current guidelines recommend that a comprehensive multimodal patient blood management strategy is critical in optimizing patient care, avoiding unnecessary transfusion of blood and blood product and limiting transfusion-related side-effects. SUMMARY: This article will highlight current guidelines in perioperative bleeding management for our most vulnerable pediatric patients with emphasis on individualized targeted intervention using point-of-care testing and specific coagulation products. PMID- 26844865 TI - Developmental fluoxetine exposure increases behavioral despair and alters epigenetic regulation of the hippocampal BDNF gene in adult female offspring. AB - A growing number of infants are exposed to selective serotonin reuptake inhibitor (SSRI) medications during the perinatal period. Perinatal exposure to SSRI medications alter neuroplasticity and increase depressive- and anxiety-related behaviors, particularly in male offspring as little work has been done in female offspring to date. The long-term effects of SSRI on development can also differ with previous exposure to prenatal stress, a model of maternal depression. Because of the limited work done on the role of developmental SSRI exposure on neurobehavioral outcomes in female offspring, the aim of the present study was to investigate how developmental fluoxetine exposure affects anxiety and depression like behavior, as well as the regulation of hippocampal brain-derived neurotrophic factor (BDNF) signaling in the hippocampus of adult female offspring. To do this female Sprague-Dawley rat offspring were exposed to prenatal stress and fluoxetine via the dam, for a total of four groups of female offspring: 1) No Stress+Vehicle, 2) No Stress+Fluoxetine, 3) Prenatal Stress+Vehicle, and 4) Prenatal Stress+Fluoxetine. Primary results show that, in adult female offspring, developmental SSRI exposure significantly increases behavioral despair measures on the forced swim test, decreases hippocampal BDNF exon IV mRNA levels, and increases levels of the repressive histone 3 lysine 27 tri-methylated mark at the corresponding promoter. There was also a significant negative correlation between hippocampal BDNF exon IV mRNA levels and immobility in the forced swim test. No effects of prenatal stress or developmental fluoxetine exposure were seen on tests of anxiety-like behavior. This research provides important evidence for the long-term programming effects of early-life exposure to SSRIs on female offspring, particularily with regard to affect related behaviors and their underlying molecular mechanisms. PMID- 26844866 TI - Effects of early pubertal exposure to di-(2-ethylhexyl) phthalate on social behavior of mice. AB - Di-(2-ethylhexyl) phthalate (DEHP), a main member of phthalates used as plasticizer in PVC plastics, is an environmental endocrine disrupter. The present study investigated the effect of DEHP on social behavior of mice following pubertal exposure (1, 10, 50, and 200mg/kg/d) from postnatal day 28 through postnatal day 42. The results showed that, in pubertal females, DEHP reduced the time spent in social play and social investigation and inhibited sociability, but a contrary effect was found in pubertal males, suggesting that the effect of DEHP on pubertal social behavior displays sex differences. In adults, DEHP reduced sociability in females and inhibited social play and social investigation in males, suggesting that early pubertal exposure to DEHP not only plays a significant role in puberty but also alters social behavior in adults. In addition, the present study showed that the higher dose of DEHP (50, 200mg/kg/d) reduced the relative weight of bilateral testis and anogenital distance of pubertal or adult males, suggesting an anti-androgenic activity of DEHP. These results suggest that early pubertal exposure to DEHP sex- and age- specifically affected the social behaviors of pubertal and even adult mice. PMID- 26844867 TI - Floral thermogenesis: An adaptive strategy of pollination biology in Magnoliaceae. AB - Floral thermogenesis plays a crucial role in pollination biology, especially in plant-pollinator interactions. We have recently explored how thermogenesis is related to pollinator activity and odour release in Magnolia sprengeri. By analyzing flower temperatures, emission of volatiles, and insect visitation, we found that floral blends released during pistillate and staminate stages were similar and coincided with sap beetle visitation. Thus, odour mimicry of staminate-stage flowers may occur during the pistillate stage and may be an adaptive strategy of Magnolia species to attract pollinators during both stages, ensuring successful pollination. In addition to the biological significance of floral thermogenesis in Magnolia species, we explored the underlying regulatory mechanisms via profiling miRNA expression in M. denudata flowers during thermogenic and non-thermogenic stages. We identified 17 miRNAs that may play regulatory roles in floral thermogenesis. Functional annotation of their target genes indicated that these miRNAs regulate floral thermogenesis by influencing cellular respiration and light reactions. These findings increase our understanding of plant-pollinator interactions and the regulatory mechanisms in thermogenic plants. PMID- 26844869 TI - Task relevance of emotional information affects anxiety-linked attention bias in visual search. AB - Task relevance affects emotional attention in healthy individuals. Here, we investigate whether the association between anxiety and attention bias is affected by the task relevance of emotion during an attention task. Participants completed two visual search tasks. In the emotion-irrelevant task, participants were asked to indicate whether a discrepant face in a crowd of neutral, middle aged faces was old or young. Irrelevant to the task, target faces displayed angry, happy, or neutral expressions. In the emotion-relevant task, participants were asked to indicate whether a discrepant face in a crowd of middle-aged neutral faces was happy or angry (target faces also varied in age). Trait anxiety was not associated with attention in the emotion-relevant task. However, in the emotion-irrelevant task, trait anxiety was associated with a bias for angry over happy faces. These findings demonstrate that the task relevance of emotional information affects conclusions about the presence of an anxiety-linked attention bias. PMID- 26844871 TI - Micromorphological characterization and label-free quantitation of small rubber particle protein in natural rubber latex. AB - Commercial natural rubber is traditionally supplied by Hevea brasiliensis, but now there is a big energy problem because of the limited resource and increasing demand. Intensive study of key rubber-related substances is urgently needed for further research of in vitro biosynthesis of natural rubber. Natural rubber is biosynthesized on the surface of rubber particles. A membrane protein called small rubber particle protein (SRPP) is a key protein associated closely with rubber biosynthesis; however, SRPP in different plants has been only qualitatively studied, and there are no quantitative reports so far. In this work, H. brasiliensis was chosen as a model plant. The microscopic distribution of SRPP on the rubber particles during the washing process was investigated by transmission electron microscopy-immunogold labeling. A label-free surface plasmon resonance (SPR) immunosensor was developed to quantify SRPP in H. brasiliensis for the first time. The immunosensor was then used to rapidly detect and analyze SRPP in dandelions and prickly lettuce latex samples. The label-free SPR immunosensor can be a desirable tool for rapid quantitation of the membrane protein SRPP, with excellent assay efficiency, high sensitivity, and high specificity. The method lays the foundation for further study of the functional relationship between SRPP and natural rubber content. PMID- 26844870 TI - Biased relevance filtering in the auditory system: A test of confidence-weighted first-impressions. AB - Although first-impressions are known to impact decision-making and to have prolonged effects on reasoning, it is less well known that the same type of rapidly formed assumptions can explain biases in automatic relevance filtering outside of deliberate behavior. This paper features two studies in which participants have been asked to ignore sequences of sound while focusing attention on a silent movie. The sequences consisted of blocks, each with a high probability repetition interrupted by rare acoustic deviations (i.e., a sound of different pitch or duration). The probabilities of the two different sounds alternated across the concatenated blocks within the sequence (i.e., short-to long and long-to-short). The sound probabilities are rapidly and automatically learned for each block and a perceptual inference is formed predicting the most likely characteristics of the upcoming sound. Deviations elicit a prediction error signal known as mismatch negativity (MMN). Computational models of MMN generally assume that its elicitation is governed by transition statistics that define what sound attributes are most likely to follow the current sound. MMN amplitude reflects prediction confidence, which is derived from the stability of the current transition statistics. However, our prior research showed that MMN amplitude is modulated by a strong first-impression bias that outweighs transition statistics. Here we test the hypothesis that this bias can be attributed to assumptions about predictable vs. unpredictable nature of each tone within the first encountered context, which is weighted by the stability of that context. The results of Study 1 show that this bias is initially prevented if there is no 1:1 mapping between sound attributes and probability, but it returns once the auditory system determines which properties provide the highest predictive value. The results of Study 2 show that confidence in the first impression bias drops if assumptions about the temporal stability of the transition-statistics are violated. Both studies provide compelling evidence that the auditory system extrapolates patterns on multiple timescales to adjust its response to prediction-errors, while profoundly distorting the effects of transition-statistics by the assumptions formed on the basis of first impressions. PMID- 26844868 TI - The putative role of Rhipicephalus microplus salivary serpins in the tick-host relationship. AB - Inflammation and hemostasis are part of the host's first line of defense to tick feeding. These systems are in part serine protease mediated and are tightly controlled by their endogenous inhibitors, in the serpin superfamily (serine protease inhibitors). From this perspective ticks are thought to use serpins to evade host defenses during feeding. The cattle tick Rhipicephalus microplus encodes at least 24 serpins, of which RmS-3, RmS-6, and RmS-17 were previously identified in saliva of this tick. In this study, we screened inhibitor functions of these three saliva serpins against a panel of 16 proteases across the mammalian defense pathway. Our data confirm that Pichia pastoris-expressed rRmS 3, rRmS-6, and rRmS-17 are likely inhibitors of pro-inflammatory and pro coagulant proteases. We show that rRmS-3 inhibited chymotrypsin and cathepsin G with stoichiometry of inhibition (SI) indices of 1.8 and 2.0, and pancreatic elastase with SI higher than 10. Likewise, rRmS-6 inhibited trypsin with SI of 2.6, chymotrypsin, factor Xa, factor XIa, and plasmin with SI higher than 10, while rRmS-17 inhibited trypsin, cathepsin G, chymotrypsin, plasmin, and factor XIa with SI of 1.6, 2.6, 2.7, 3.4, and 9.0, respectively. Additionally, we observed the formation of irreversible complexes between rRmS-3 and chymotrypsin, rRmS-6/rRmS-17 and trypsin, and rRmS-3/rRmS-17 and cathepsin G, which is consistent with typical mechanism of inhibitory serpins. In blood clotting assays, rRmS-17 delayed plasma clotting by 60 s in recalcification time assay, while rRmS-3 and rRmS-6 did not have any effect. Consistent with inhibitor function profiling data, 2.0 MUM rRmS-3 and rRmS-17 inhibited cathepsin G activated platelet aggregation in a dose-responsive manner by up to 96% and 95% respectively. Of significant interest, polyclonal antibodies blocked inhibitory functions of the three serpins. Also notable, antibodies to Amblyomma americanum, Ixodes scapularis, and Rhipicephalus sanguineus tick saliva proteins cross reacted with the three R. microplus saliva serpins, suggesting the potential of these proteins as candidates for universal anti-tick vaccines. PMID- 26844872 TI - Renal sinus fat volume on computed tomography in middle-aged patients at risk for cardiovascular disease and its association with coronary artery calcification. AB - OBJECTIVE: Renal sinus fat (RSF) behaves as one of the perivascular fats, however RSF volume (RSFV) is considerably affected by visceral adipose tissue volume (VTAV). The ratio of RSFV to VATV (RSFV/VATV ratio) can be an index of regional perivascular fat accumulation corrected for the influence of VATV. The aim of this study was to investigate the relation between RSFV/VATV ratio and coronary artery calcium (CAC) in patients with suspected coronary artery disease. METHODS: One hundred and eighty-nine patients (mean age 66.7 +/- 10.2; 72% men) underwent ECG-gated cardiac computed tomography (CT) and unenhanced abdominal CT. CAC score (CACS) was assessed using axial CT images. RSFV was measured by partially manipulated segmentation of the right kidney. VATV was automatically quantified in the upper abdomen. Logistic and correlation analyses were performed to examine the correlations between CAC, RSFV/VATV ratio, and risk factors of cardiovascular diseases in total and subgroups classified by the patients' age. RESULTS: Log transformed RSFV/VATV ratio was associated with CAC presence in 112 middle-aged patients less than 69 years of age as well as total. This association remained significant after multivariate adjustment only in the middle-aged patients (OR 15.9, 95% CI 1.15-218.8). In total, RSFV/VATV ratio (r = 0.228, p = 0.002) and age (r = 0.316, p < 0.001) correlated with CACS on univariate analyses, but only age correlated on multivariate analyses. RSFV/VATV ratio correlated with CACS in the middle-aged patients (r = 0.418, p < 0.001), as well as on multivariate analyses. CONCLUSIONS: We demonstrated that RSFV/VATV could be an independent risk indicator of CAC in the middle-aged patients. PMID- 26844873 TI - Long-term Effects of Octreotide on Liver Volume in Patients With Polycystic Kidney and Liver Disease. AB - BACKGROUND & AIMS: Short-term studies have shown that somatostatin analogues are effective in patients with polycystic kidney and liver disease. We evaluated the long-term effects of long-acting release octreotide (octreotide LAR), a somatostatin inhibitor, vs placebo in these patients. METHODS: We performed a controlled study of adults with polycystic kidney and liver disease (estimated glomerular filtration rate, 40 mL/min/1.73m(2) or more) at a single center in Italy. We analyzed data from 27 patients randomly assigned to groups given octreotide LAR (40 mg, n = 14) or placebo (n = 13) each month for 3 years. The primary outcome was absolute and percentage change in total liver volume (TLV), which was measured by magnetic resonance imaging at baseline, after 3 years of treatment, and then 2 years after treatment ended. RESULTS: Baseline characteristics were similar between groups. After 3 years, TLV decreased by 130.2 +/- 133.2 mL in patients given octreotide LAR (7.8% +/- 7.4%) (P = .003) but increased by 144.3 +/- 316.8 mL (6.1% +/- 14.1%) in patients given placebo. Change vs baseline differed significantly between groups (P = .004). Two years after treatment ended, TLV had decreased 14.4 +/- 138.4 mL (0.8% +/- 9.7%) from baseline in patients given octreotide LAR but increased by 224.4 +/- 331.7 mL (11.0% +/- 14.4%) in patients given placebo. Changes vs baseline still differed significantly between groups (P = .046). Decreases in TLV were similar in each sex; the change in TLV was greatest among subjects with larger baseline TLV. No patient withdrew because of side effects. CONCLUSIONS: In a placebo-controlled study of patients with polycystic kidney and liver disease, 3 years of treatment with octreotide LAR significantly reduced liver volume; reductions were maintained for 2 years after treatment ended. Octreotide LAR was well-tolerated. ClinicalTrials.gov number: NCT02119052. PMID- 26844874 TI - Association Between Circulating Levels of C-Reactive Protein and Interleukin-6 and Risk of Inflammatory Bowel Disease. AB - BACKGROUND & AIMS: There is evidence that immune dysfunction precedes symptoms of inflammatory bowel disease (IBD) by several years. Characterization of preclinical systemic inflammation could contribute to the understanding of the biology of IBD and, ultimately, facilitate development of strategies for early disease detection and intervention. We evaluated associations between circulating levels of interleukin-6 (IL6) and high-sensitivity C-reactive protein (hsCRP) and diagnosis of incident Crohn's disease (CD) or ulcerative colitis (UC). METHODS: We conducted a nested case-control study of participants enrolled in 2 population based, nationwide, prospective cohort studies (the Nurses' Health Study and the Nurses' Health Study II). We analyzed blood specimens, collected before diagnosis, from 83 persons with CD, 90 persons with UC, and 344 matched individuals without IBD (control subjects). Plasma levels of hsCRP and IL6 were measured. We investigated associations between each inflammatory marker and IBD risk using multivariable logistic regression models to adjust for potential confounding exposures. RESULTS: Compared with the lowest quintile of IL6 level, the highest quintile was associated with an odds ratio (OR) of 4.68 (95% confidence interval, 1.91-11.46) for CD (Ptrend < .001) and an OR of 3.43 (95% confidence interval, 1.44-8.15) for UC (Ptrend = .004). The highest quintile of hsCRP level, compared with the lowest quintile, was associated with an OR of 2.82 (95% confidence interval, 1.15-6.87) for CD (Ptrend = .019) and an OR of 1.79 (95% confidence interval, 0.80-3.99) for UC (Ptrend = .015). CONCLUSIONS: Plasma levels of IL6 and hsCRP before diagnosis are associated with risk of incident CD and UC. Subclinical levels of systemic inflammation may be a feature of an early disease state that precedes the development of symptomatic IBD. PMID- 26844875 TI - Endoscope Holders in Cranial Neurosurgery: Part I-Technology, Trends, and Implications. AB - OBJECTIVE: Cranial neuroendoscopy is becoming increasingly popular. Endoscopes may be used free-hand or with endoscope holders (EH). The aim of this paper is to summarize the evolution of EH and attempt an overview of currently available devices, features, and usage, identifying weaknesses and focusing on feasibility. METHODS: A systematic review was conducted on Pubmed, OvidSP, Ebsco, and Google Scholar. Targeted search through cross-references was also implemented, followed by personal contacts, interviews, company websites, and operating manuals. A pilot survey was performed to acquire an impression of the current state of usage. This was conducted by approaching surgeons from several countries via e mail and online through a neurosurgical exchange forum. A more extensive survey will follow as Part II. RESULTS: EH may be divided into manual and pneumatic. The use of micromanipulators is sometimes implemented. Different characteristics have been described, such as pneumatic, mechanical, friction, micromanipulator, robotic, hybrid, air-locking, and voice-control. Twenty eight surgeons responded. The majority (75%) do not routinely use EH. The rest use EH mainly for intraventricular rather than skull base procedures. Nearly all surgeons (96%) stated using a second surgeon regularly. Reported weaknesses included crude movements, downward drift, loss of depth perception, lack of flexibility, iatrogenic injury, cost, and bulky construction. CONCLUSIONS: Although EH have a role in neuroendoscopy, their use seems to be limited and their features regarded as suboptimal. There are no clear indications regarding the procedures that should be performed using EH. Many factors affect the implication of EH, including safety, type of surgery, surgeon's preference, and mechanical properties. PMID- 26844877 TI - Gamma Knife Surgery for Metastatic Brain Tumors from Gynecologic Cancer. AB - OBJECTIVE: The incidences of metastatic brain tumors from gynecologic cancer have increased. The results of Gamma Knife surgery (GKS) for the treatment of patients with brain metastases from gynecologic cancer (ovarian, endometrial, and uterine cervical cancers) were retrospectively analyzed to identify the efficacy and prognostic factors for local tumor control and survival. METHODS: The medical records were retrospectively reviewed of 70 patients with 306 tumors who underwent GKS for brain metastases from gynecologic cancer between January 1995 and December 2013 in our institution. RESULTS: The primary cancers were ovarian in 33 patients with 147 tumors and uterine in 37 patients with 159 tumors. Median tumor volume was 0.3 cm(3). Median marginal prescription dose was 20 Gy. The local tumor control rates were 96.4% at 6 months and 89.9% at 1 year. There was no statistically significant difference between ovarian and uterine cancers. Higher prescription dose and smaller tumor volume were significantly correlated with local tumor control. Median overall survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and solitary brain metastasis were significantly correlated with satisfactory overall survival. Median activities of daily living (ADL) preservation survival time was 8 months. Primary ovarian cancer, controlled extracranial metastases, and higher Karnofsky Performance Status score were significantly correlated with better ADL preservation. CONCLUSIONS: GKS is effective for control of tumor progression in patients with brain metastases from gynecologic cancer, and may provide neurologic benefits and preservation of the quality of life. PMID- 26844876 TI - Moyamoya Disease in a Patient with VACTERL Association. AB - BACKGROUND: VACTERL association is characterized by a group of congenital malformations that tend to occur together. Rarely, concurrent cerebrovascular abnormalities have been reported. In this article, we present the first reported case of moyamoya disease in a patient with VACTERL association. CASE DESCRIPTION: The patient presented in the neonatal period with esophageal atresia with distal tracheoesophageal fistula as well as an imperforate anus. He also had a ventricular septal defect and persistent foramen ovale. At age 11 years, he developed seizures and was diagnosed with moyamoya disease, for which he underwent bilateral pial synagiosis. CONCLUSIONS: Our report adds moyamoya disease to the spectrum of rare diseases that may occur in the context of VACTERL association. Further studies may reveal whether a common pathophysiology exists between the 2 conditions. Our patient's congenital heart disease and the association between renovascular and cardiac disease with moyamoya may suggest a systemic vasculopathy. Moyamoya should be considered in children with VACTERL association who present with neurologic deficits or seizures. PMID- 26844878 TI - Surgical Management of Dural Arteriovenous Fistula After Craniotomy: Case Report and Review of Literature. AB - BACKGROUND: Development of dural arteriovenous fistula (dAVF) with cortical venous drainage at the site of previous craniotomy is a rare manifestation of nontraumatic subarachnoid hemorrhage (SAH). The authors present a case of postcraniotomy dAVF formation and discuss plausible underlying mechanisms of fistula formation and treatment options as well as review the literature. CASE DESCRIPTION: A 62-year-old man, who had undergone craniotomy 2 decades previously, presented with SAH. Workup revealed a low-flow dAVF with leptomeningeal venous drainage at the posterior margin of the craniotomy. Surgical resection of fistula was undertaken that resulted in cure. CONCLUSIONS: Spontaneous SAH in patients with a previous history of an intracranial procedure (e.g., craniotomy, ventriculostomy) should prompt detailed imaging evaluation. In the absence of vascular disease, meticulous review of the angiogram must be undertaken to rule out dAVF at the procedure site and it should be treated definitively. PMID- 26844879 TI - Perineural Spread of Renal Cell Carcinoma: A Case Illustration with a Proposed Anatomic Mechanism and a Review of the Literature. AB - INTRODUCTION: Perineural spread (PNS) is an unusual mechanism of tumor extension and has been typically reported in squamous cell carcinoma, adenocystic carcinoma, and desmoplastic melanoma. Our group has previously demonstrated PNS in rectal, prostate, bladder, and cervical cancer from the primary site along the autonomic nerves to the major somatic nerves and even intradurally. We believe similar principles apply to renal cell carcinoma (RCC) as well, despite the different anatomy. CASE DESCRIPTION: We performed a retrospective search to identify cases of intradural-extramedullary metastases of RCC caused by PNS. Strict anatomic and imaging inclusion criteria were defined: only lesions located between T6 and L3 were included, and PNS as a potential cause had to be supported by imaging evidence. Although 3 cases of spinal intradural metastases were identified, only one met our strict inclusion criteria. A 61-year-old woman developed a late intradural-extramedullary metastasis of RCC 16 years after the original diagnosis that we believe represents an example of visceral organ PNS. CONCLUSIONS: RCC can propagate via PNS from the primary tumor along the autonomic nerves to the aorticorenal, celiac, and mesenteric ganglia and then along the thoracic and lumbar splanchnic nerves to the corresponding spinal nerves and intradurally. We present radiologic evidence together with the review of the literature to support the premise that PNS of RCC not only occurs but goes unrecognized. PMID- 26844880 TI - Expression of polysialyltransferases (STX and PST) in adult rat olfactory bulb after an olfactory associative discrimination task. AB - Neuronal plasticity and neurogenesis occur in the adult hippocampus and in other brain structures such as the olfactory bulb and often involve the neural cell adhesion molecule NCAM. During an olfactory associative discrimination learning task, NCAM polysialylation triggers neuronal plasticity in the adult hippocampus. The PST enzyme likely modulates this polysialylation, but not STX, a second sialyltransferase. How the two polysialyltransferases are involved in the adult olfactory bulb remains unknown. We addressed this question by investigating the effect of olfactory associative learning on plasticity and neurogenesis. After a hippocampo-dependent olfactory associative task learning, we measured the expression of both PST and STX polysialyltransferases in the olfactory bulbs of adult rats using quantitative PCR. In parallel, immunohistochemistry was used to evaluate both NCAM polysialylation level and newly-born cells, with or without learning. After learning, no changes were observed neither in the expression level of PST and NCAM polysialylation, nor in STX gene expression level and newly born cells number in the olfactory bulb. PMID- 26844881 TI - Bringing to Light Hidden Elasticity in the Liquid State Using In-Situ Pretransitional Liquid Crystal Swarms. AB - The present work reveals that at the sub-millimeter length-scale, molecules in the liquid state are not dynamically free but elastically correlated. It is possible to "visualize" these hidden elastic correlations by using the birefringent properties of pretransitional swarms persistent in liquids presenting a weak first order transition. The strategy consists in observing the optical response of the isotropic phase of mesogenic fluids to a weak (low energy) mechanical excitation. We show that a synchronized optical response is observable at frequencies as low as 0.01Hz and at temperatures far away from any phase transition (up to at least 15 degrees C above the transition). The observation of a synchronized optical signal at very low frequencies points out a collective response and supports the existence of long-range elastic (solid-like) correlations existing at the sub-millimeter length-scale in agreement to weak solid-like responses already identified in various liquids including liquid water. This concept of elastically linked molecules differs deeply with the academic view of molecules moving freely in the liquid state and has profound consequences on the mechanisms governing collective effects as glass formation, gelation and transport, or synchronized processes in physiological media. PMID- 26844882 TI - Novel Roles for Kv7 Channels in Shaping Histamine-Induced Contractions and Bradykinin-Dependent Relaxations in Pig Coronary Arteries. AB - Voltage-gated Kv7 channels are inhibited by agonists of Gq-protein-coupled receptors, such as histamine. Recent works have provided evidence that inhibition of vascular Kv7 channels may trigger vessel contractions. In this study, we investigated how Kv7 activity modulates the histamine-induced contractions in "healthy" and metabolic syndrome (MetS) pig right coronary arteries (CAs). We performed isometric tension and immunohistochemical studies with domestic, lean Ossabaw, and MetS Ossabaw pig CAs. We found that neither the Kv7.2/Kv7.4/Kv7.5 activator ML213 nor the general Kv7 inhibitor XE991 altered the tension of CA rings under preload, indicating that vascular Kv7 channels are likely inactive in the preloaded rings. Conversely, ML213 potently dilated histamine-pre-contracted CAs, suggesting that Kv7 channels are activated during histamine applications and yet partially inhibited by histamine. Immunohistochemistry analysis revealed strong Kv7.4 immunostaining in the medial and intimal layers of the CA wall, whereas Kv7.5 immunostaining intensity was strong in the intimal but weak in the medial layers. The medial Kv7 immunostaining was significantly weaker in MetS Ossabaw CAs as compared to lean Ossabaw or domestic CAs. Consistently, histamine pre-contracted MetS Ossabaw CAs exhibited attenuated ML213-dependent dilations. In domestic pig CAs, where medial Kv7 immunostaining intensity was stronger, histamine-induced contractions spontaneously decayed to ~31% of the peak amplitude within 4 minutes. Oppositely, in Ossabaw CAs, where Kv7 immunostaining intensity was weaker, the histamine-induced contractions were more sustained. XE991 pretreatment significantly slowed the decay rate of histamine-induced contractions in domestic CAs, supporting the hypothesis that increased Kv7 activity correlates with a faster rate of histamine-induced contraction decay. Alternatively, XE991 significantly decreased the amplitude of bradykinin dependent dilations in pre-contracted CAs. We propose that in CAs, a decreased expression or a loss of function of Kv7 channels may lead to sustained histamine induced contractions and reduced endothelium-dependent relaxation, both risk factors for coronary spasm. PMID- 26844884 TI - Correction: Shifting Milestones of Natural Sciences: The Ancient Egyptian Discovery of Algol's Period Confirmed. PMID- 26844883 TI - Fear of Movement and Low Self-Efficacy Are Important Barriers in Physical Activity after Renal Transplantation. AB - BACKGROUND: Physical activity (PA) and exercise are commonly used as preventive measures for cardiovascular disease in the general population, and could be effective in the management of post-transplantation cardiovascular risk. PA levels are low after renal transplantation and very few renal transplant recipients (RTR) meet the PA guidelines. Identification of barriers to regular PA is important to identify targets for intervention to improve PA levels after renal transplantation. We investigated fear of movement and physical self efficacy as barriers to PA in RTR. METHODS: RTR were investigated between 2001 2003. The Tampa Score of Kinesiophobia-Dutch Version (TSK-11) was used to assess fear of movement. Physical self-efficacy was measured with the LIVAS-scale. PA was assessed using validated questionnaires (Tecumseh Occupational Activity Questionnaire and the Minnesota Leisure Time Physical Activity Questionnaire). RESULTS: A total of 487 RTR (age 51+/-12 years, 55% men) were studied. Median score [interquartile range] on TSK-11 was 22 [17-26]. Low physical self-efficacy (Exp B:0.41[0.31-0.54], p<0.001) and history of myocardial infarction, transient ischemic attack and cerebrovascular accident (Exp B:1.30[1.03-1.63],p = 0.03) were independent determinants for fear of movement. Fear of movement was associated with lower daily PA, occupational, sports and leisure time PA. Mediation-analysis showed that a large part (73%) of the effect of fear of movement on PA was explained by low physical self-efficacy. CONCLUSIONS: This study was the first to examine fear of movement and self-efficacy in relation to PA in RTR. Fear of movement was associated with a low PA level, and the larger part of this relation was mediated by low physical self-efficacy. Both fear of movement and physical self-efficacy level are important targets for intervention during rehabilitation after renal transplantation. PMID- 26844885 TI - Evaluation of two methods for direct detection of Fusarium spp. in water. AB - Fusarium is a waterborne fungus that causes severe infections especially in patients with prolonged neutropenia. Traditionally, the detection of Fusarium in water is done by culturing which is difficult and time consuming. A faster method is necessary to prevent exposure of susceptible patients to contaminated water. The objective of this study was to develop a molecular technique for direct detection of Fusarium in water. A direct DNA extraction method from water was developed and coupled to a genus-specific PCR, to detect 3 species of Fusarium (verticillioides, oxysporum and solani). The detection limits were 10 cells/L and 1 cell/L for the molecular and culture methods, respectively. To our knowledge, this is the first method developed to detect Fusarium directly from water. PMID- 26844886 TI - Multi-laboratory survey of qPCR enterococci analysis method performance in U.S. coastal and inland surface waters. AB - Quantitative polymerase chain reaction (qPCR) has become a frequently used technique for quantifying enterococci in recreational surface waters, but there are several methodological options. Here we evaluated how three method permutations, type of mastermix, sample extract dilution and use of controls in results calculation, affect method reliability among multiple laboratories with respect to sample interference. Multiple samples from each of 22 sites representing an array of habitat types were analyzed using EPA Method 1611 and 1609 reagents with full strength and five-fold diluted extracts. The presence of interference was assessed three ways: using sample processing and PCR amplifications controls; consistency of results across extract dilutions; and relative recovery of target genes from spiked enterococci in water sample compared to control matrices with acceptable recovery defined as 50 to 200%. Method 1609, which is based on an environmental mastermix, was found to be superior to Method 1611, which is based on a universal mastermix. Method 1611 had over a 40% control assay failure rate with undiluted extracts and a 6% failure rate with diluted extracts. Method 1609 failed in only 11% and 3% of undiluted and diluted extracts analyses. Use of sample processing control assay results in the delta-delta Ct method for calculating relative target gene recoveries increased the number of acceptable recovery results. Delta-delta tended to bias recoveries from apparent partially inhibitory samples on the high side which could help in avoiding potential underestimates of enterococci--an important consideration in a public health context. Control assay and delta-delta recovery results were largely consistent across the range of habitats sampled, and among laboratories. The methodological option that best balanced acceptable estimated target gene recoveries with method sensitivity and avoidance of underestimated enterococci densities was Method 1609 without extract dilution and using the delta-delta calculation method. The applicability of this method can be extended by the analysis of diluted extracts to sites where interference is indicated but, particularly in these instances, should be confirmed by augmenting the control assays with analyses for target gene recoveries from spiked target organisms. PMID- 26844887 TI - EEPD1: Breaking and Rescuing the Replication Fork. PMID- 26844888 TI - Truthful Channel Sharing for Self Coexistence of Overlapping Medical Body Area Networks. AB - As defined by IEEE 802.15.6 standard, channel sharing is a potential method to coordinate inter-network interference among Medical Body Area Networks (MBANs) that are close to one another. However, channel sharing opens up new vulnerabilities as selfish MBANs may manipulate their online channel requests to gain unfair advantage over others. In this paper, we address this issue by proposing a truthful online channel sharing algorithm and a companion protocol that allocates channel efficiently and truthfully by punishing MBANs for misreporting their channel request parameters such as time, duration and bid for the channel. We first present an online channel sharing scheme for unit-length channel requests and prove that it is truthful. We then generalize our model to settings with variable-length channel requests, where we propose a critical value based channel pricing and preemption scheme. A bid adjustment procedure prevents unbeneficial preemption by artificially raising the ongoing winner's bid controlled by a penalty factor lambda. Our scheme can efficiently detect selfish behaviors by monitoring a trust parameter alpha of each MBAN and punish MBANs from cheating by suspending their requests. Our extensive simulation results show our scheme can achieve a total profit that is more than 85% of the offline optimum method in the typical MBAN settings. PMID- 26844889 TI - Community Resilience throughout the Lifespan--The Potential Contribution of Healthy Elders. AB - An increase in the exposure and predisposition of civilian populations to disasters has been recorded in the last decades. In major disasters, as demonstrated recently in Nepal (2015) and previously in Haiti (2010), external aid is vital, yet in the first hours after a disaster, communities must usually cope alone with the challenge of providing emergent lifesaving care. Communities therefore need to be prepared to handle emergency situations. Mapping the needs of the populations within their purview is a trying task for decision makers and community leaders. In this context, the elderly are traditionally treated as a susceptible population with special needs. The current study aimed to explore variations in the level of community resilience along the lifespan. The study was conducted in nine small to mid-size towns in Israel between August and November 2011 (N = 885). The Conjoint Community Resiliency Assessment Measure (CCRAM), a validated instrument for community resilience assessment, was used to examine the association between age and community resilience score. Statistical analysis included spline and logistic regression models that explored community resiliency over the lifespan in a way that allowed flexible modeling of the curve without prior constraints. This innovative statistical approach facilitated identification of the ages at which trend changes occurred. The study found a significant rise in community resiliency scores in the age groups of 61-75 years as compared with younger age bands, suggesting that older people in good health may contribute positively to building community resiliency for crisis. Rather than focusing on the growing medical needs and years of dependency associated with increased life expectancy and the resulting climb in the proportion of elders in the population, this paper proposes that active "young at heart" older people can be a valuable resource for their community. PMID- 26844890 TI - Laparoscopic Pectopexy: A Biomechanical Analysis. AB - INTRODUCTION: Pectopexy, a laparoscopic method for prolapse surgery, showed promising results in recent literature. Further improving this approach by reducing surgical time may decrease complication rates and patient morbidity. Since laparoscopic suturing is a time consuming task, we propose a single suture /mesh ileo-pectineal ligament fixation as opposed to the commonly used continues approach. METHODS: Evaluation was performed on human non-embalmed, fresh cadaver pelves. A total of 33 trials was performed. Eight female pelves with an average age of 75, were used. This resulted in 16 available ligaments. Recorded parameters were ultimate load, displacement at failure and stiffness. RESULTS: The ultimate load for the mesh + simplified single "interrupted" suture (MIS) group was 35 (+/- 12) N and 48 (+/- 7) N for the mesh + continuous suture (MCS) group. There was no significant difference in the ultimate load between both groups (p> 0.05). This was also true for displacement at failure measured at 37 (+/- 12) mm and 36 (+/-5) mm respectively. There was also no significant difference in stiffness and failure modes. CONCLUSION: Given the data above we must conclude that a continuous suture is not necessary in laparoscopic mesh / ileo-pectineal ligament fixation during pectopexy. Ultimate load and displacement at failure results clearly indicate that a single suture is not inferior to a continuous approach. The use of two single sutures may improve ligamental fixation. However, overall stability should not benefit since the surgical mesh remains the limiting factor. PMID- 26844891 TI - Primates in Human-Modified and Fragmented Landscapes: The Conservation Relevance of Modelling Habitat and Disturbance Factors in Density Estimation. AB - Accurate density estimations of threatened animal populations is essential for management and conservation. This is particularly critical for species living in patchy and altered landscapes, as is the case for most tropical forest primates. In this study, we used a hierarchical modelling approach that incorporates the effect of environmental covariates on both the detection (i.e. observation) and the state (i.e. abundance) processes of distance sampling. We applied this method to already published data on three arboreal primates of the Udzungwa Mountains of Tanzania, including the endangered and endemic Udzungwa red colobus (Procolobus gordonorum). The area is a primate hotspot at continental level. Compared to previous, 'canonical' density estimates, we found that the inclusion of covariates in the modelling makes the inference process more informative, as it takes in full account the contrasting habitat and protection levels among forest blocks. The correction of density estimates for imperfect detection was especially critical where animal detectability was low. Relative to our approach, density was underestimated by the canonical distance sampling, particularly in the less protected forest. Group size had an effect on detectability, determining how the observation process varies depending on the socio-ecology of the target species. Lastly, as the inference on density is spatially-explicit to the scale of the covariates used in the modelling, we could confirm that primate densities are highest in low-to-mid elevations, where human disturbance tend to be greater, indicating a considerable resilience by target monkeys in disturbed habitats. However, the marked trend of lower densities in unprotected forests urgently calls for effective forest protection. PMID- 26844893 TI - Filaggrin and Skin Barrier Function. AB - The skin barrier function is greatly dependent on the structure and composition of the uppermost layer of the epidermis, the stratum corneum (SC), which is made up of flattened anucleated cells surrounded by highly organized and continuous lipid matrix. The interior of the corneocytes consists mainly of keratin filaments aggregated by filaggrin (FLG) protein. Next, together with several other proteins, FLG is cross-linked into a mechanically robust cornified cell envelope providing a scaffold for the extracellular lipid matrix. In addition to its role for the SC structural and mechanical integrity, FLG degradation products account in part for the water-holding capacity and maintenance of acidic pH of the SC, both crucial for the epidermal barrier homoeostasis by regulating activity of multiple enzymes that control desquamation, lipid synthesis and inflammation. The major determinant of FLG expression in the skin are loss-of function mutations in FLG, the strongest genetic risk factor for atopic dermatitis (AD), an inflammatory skin disease characterized by a reduced skin barrier function. The prevalence of FLG mutations varies greatly among different populations and ranges from about 10% in Northern Europeans to less than 1% in the African populations. An impaired skin barrier facilitates absorption of potentially hazardous chemicals, which might cause adverse effects in the skin, such as contact dermatitis, or systemic toxicity after their passage into blood. In another direction, a leaky epidermal barrier will lead to enhanced loss of water from the skin. A recent study has shown that even subtle increase in epidermal water loss in newborns increases the risk for AD. Although there are multiple modes of action by which FLG might affect skin barrier it is still unclear whether and how FLG deficiency leads to the reduced skin barrier function. This chapter summarizes the current knowledge in this field obtained from clinical studies, and animal and in vitro models of FLG deficiency. PMID- 26844892 TI - Early Life Conditions and Physiological Stress following the Transition to Farming in Central/Southeast Europe: Skeletal Growth Impairment and 6000 Years of Gradual Recovery. AB - Early life conditions play an important role in determining adult body size. In particular, childhood malnutrition and disease can elicit growth delays and affect adult body size if severe or prolonged enough. In the earliest stages of farming, skeletal growth impairment and small adult body size are often documented relative to hunter-gatherer groups, though this pattern is regionally variable. In Central/Southeast Europe, it is unclear how early life stress, growth history, and adult body size were impacted by the introduction of agriculture and ensuing long-term demographic, social, and behavioral change. The current study assesses this impact through the reconstruction and analysis of mean stature, body mass, limb proportion indices, and sexual dimorphism among 407 skeletally mature men and women from foraging and farming populations spanning the Late Mesolithic through Early Medieval periods in Central/Southeast Europe (~7100 calBC to 850 AD). Results document significantly reduced mean stature, body mass, and crural index in Neolithic agriculturalists relative both to Late Mesolithic hunter-gatherer-fishers and to later farming populations. This indication of relative growth impairment in the Neolithic, particularly among women, is supported by existing evidence of high developmental stress, intensive physical activity, and variable access to animal protein in these early agricultural populations. Among subsequent agriculturalists, temporal increases in mean stature, body mass, and crural index were more pronounced among Central European women, driving declines in the magnitude of sexual dimorphism through time. Overall, results suggest that the transition to agriculture in Central/Southeast Europe was challenging for early farming populations, but was followed by gradual amelioration across thousands of years, particularly among Central European women. This sex difference may be indicative, in part, of greater temporal variation in the social status afforded to young girls, in their access to resources during growth, and/or in their health status than was experienced by men. PMID- 26844894 TI - Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic Dermatitis Patients. AB - Human skin acts as a primary barrier between the body and its environment. Crucial for this skin barrier function is the lipid matrix in the outermost layer of the skin, the stratum corneum (SC). Two of its functions are (1) to prevent excessive water loss through the epidermis and (2) to avoid that compounds from the environment permeate into the viable epidermal and dermal layers and thereby provoke an immune response. The composition of the SC lipid matrix is dominated by three lipid classes: cholesterol, free fatty acids and ceramides. These lipids adopt a highly ordered, 3-dimensional structure of stacked densely packed lipid layers (lipid lamellae): the lateral and lamellar lipid organization. The way in which these lipids are ordered depends on the composition of the lipids. One very common skin disease in which the SC lipid barrier is affected is atopic dermatitis (AD). This review addresses the SC lipid composition and organization in healthy skin, and elaborates on how these parameters are changed in lesional and nonlesional skin of AD patients. Concerning the lipid composition, the changes in the three main lipid classes and the importance of the carbon chain lengths of the lipids are discussed. In addition, this review addresses how these changes in lipid composition induce changes in lipid organization and subsequently correlate with an impaired skin barrier function in both lesional and nonlesional skin of these patients. Furthermore, the effect of filaggrin and mutations in the filaggrin gene on the SC lipid composition is critically discussed. Also, the breakdown products of filaggrin, the natural moisturizing factor molecules and its relation to SC-pH is described. Finally, the paper discusses some major changes in epidermal lipid biosynthesis in patients with AD and other related skin diseases, and how inflammation has a deteriorating effect on the SC lipids and SC biosynthesis. The review ends with perspectives on future studies in relation to other skin diseases. PMID- 26844895 TI - Importance of Tight Junctions in Relation to Skin Barrier Function. AB - Tight junctions (TJs) are complex cell-cell junctions that form a barrier in the stratum granulosum of mammalian skin. Besides forming a barrier themselves, TJs influence other skin barriers, e.g. the stratum corneum barrier, and are influenced by other skin barriers, e.g. by the chemical, the microbiome, or the immunological barrier and likely by the basement membrane. This review summarizes the dynamic interaction of the TJ barrier with other barriers in the skin and the central role of TJs in skin barrier function. PMID- 26844896 TI - Antimicrobial Peptides, Infections and the Skin Barrier. AB - The skin serves as a strong barrier protecting us from invading pathogens and harmful organisms. An important part of this barrier comes from antimicrobial peptides (AMPs), which are small peptides expressed abundantly in the skin. AMPs are produced in the deeper layers of the epidermis and transported to the stratum corneum, where they play a vital role in the first line of defense against potential pathogens. Numerous AMPs exist, and they have a broad antibiotic-like activity against bacteria, fungi and viruses. They also act as multifunctional effector molecules, linking innate and adaptive immune responses. AMPs play an essential part in maintaining an optimal and functional skin barrier - not only by direct killing of pathogens, but also by balancing immune responses and interfering in wound healing, cell differentiation, reepithelialization and their synergistic interplay with the skin microflora. PMID- 26844897 TI - Biological Variation in Skin Barrier Function: From A (Atopic Dermatitis) to X (Xerosis). AB - The skin barrier, formed by the stratum corneum, envelops our bodies and provides an essential protective function. However, this barrier function differs between individuals due to biological variation. This variation arises as a result of inherited genetic variants, negative environmental or extrinsic factors, and age. A multitude of genetic changes determine a person's predisposition to a skin barrier defect and consequently their risk of developing a dry skin condition, such as atopic dermatitis. Extrinsic factors, including the weather and detrimental skin care practices, interact with these genetic changes to determine the severity of the defect and additively increase the risk of developing dry skin conditions. How these dry skin conditions present clinically, and how they persist and progress depends very much on a person's age. Understanding how the skin barrier varies between individuals, how it differs based on clinical presentation, and how it alters with age is important in developing optimum therapies to maintain healthy skin that provides the best protection. PMID- 26844898 TI - Methods for the Assessment of Barrier Function. AB - Due to the ease of skin accessibility, a large variety of invasive and noninvasive in vitro and in vivo methods have been developed to study barrier function. The measurement of the transepidermal water loss (TEWL) is most widely used in clinical studies. The different methods of determining TEWL, as well as skin hydration, skin pH, tape stripping and other modern less widely used methods to assess skin barrier function, are reviewed, including Raman spectroscopy and imaging methods such as optical coherence tomography and laser scanning microscopy. The modern imaging methods are important developments in the last decades which, however, determine the structure and, hence, cannot replace the measurement of TEWL in questions related to function. PMID- 26844899 TI - In vivo Raman Confocal Spectroscopy in the Investigation of the Skin Barrier. AB - The epidermal barrier, predominantly attributed to the stratum corneum (SC), is the outermost part of our body that comprises multiple defensive functions against exogenous attacks and the loss of body substances, e.g. water. A novel investigative method, in vivo Raman confocal spectroscopy (RCS), is employed to study the composition of the epidermal barrier and compounds penetrating the epidermis both in a space-resolved manner. By using this method, a semiquantitative analysis of skin barrier constituents can be evaluated, namely SC lipids, natural moisturizing factor components and sweat constituents. The technique enables to examine epidermal barrier impairment in experimental settings as well as the penetration of exogenous substances into the epidermis, e.g. retinol. RCS can reveal microcompositional changes in the skin barrier as a function of age. We also review the use of RCS in studying antioxidant defense components. This chapter discusses the application of in vivo RCS in the investigation of the epidermal barrier. PMID- 26844900 TI - Irritants and Skin Barrier Function. AB - The barrier response to irritant challenge involves complex biologic events and can be modulated by various environmental, exposure and host-related factors. Irritant damage to the epidermal barrier elicits a cascade of homeostatic or pathologic responses that could be investigated by both in vitro and in vivo methods providing different information at biochemical and functional level. The present chapter summarizes the changes in key barrier function parameters following irritant exposure with focus on experimental controlled in vivo human skin studies. PMID- 26844901 TI - Skin Barrier Function and Allergens. AB - The skin is an important barrier protecting us from mechanical insults, microorganisms, chemicals and allergens, but, importantly, also reducing water loss. A common hallmark for many dermatoses is a compromised skin barrier function, and one could suspect an elevated risk of contact sensitization (CS) and allergy following increased penetration of potential allergens. However, the relationship between common dermatoses such as psoriasis, atopic dermatitis (AD) and irritant contact dermatitis (ICD) and the development of contact allergy (CA) is complex, and depends on immunologic responses and skin barrier status. Psoriasis has traditionally been regarded a Th1-dominated disease, but the discovery of Th17 cells and IL-17 provides new and interesting information regarding the pathogenesis of the disease. Research suggests an inverse relationship between psoriasis and CA, possibly due to increased levels of Th17 cells and its associated cytokines. As for AD, a positive association to CS has been established in epidemiological studies, but is still unresolved. Experimental studies show, however, an inverse relationship between AD and CS. The opposing and antagonistic influences of Th1 (CS) and Th2 (AD) have been proposed as an explanation. Finally, there is convincing evidence that exposure to irritants increases the risk of CS, and patients with ICD are, therefore, at great risk of developing CA. Skin irritation leads to the release of IL-1 and TNF alpha, which affects the function of antigen-presenting cells and promotes their migration to local lymph nodes, thus increasing the probability of CS and ultimately the development of CA. PMID- 26844902 TI - Penetration through the Skin Barrier. AB - The skin is a strong and flexible organ with barrier properties essential for maintaining homeostasis and thereby human life. Characterizing this barrier is the ability to prevent some chemicals from crossing the barrier while allowing others, including medicinal products, to pass at varying rates. During recent decades, the latter has received increased attention as a route for intentionally delivering drugs to patients. This has stimulated research in methods for sampling, measuring and predicting percutaneous penetration. Previous chapters have described how different endogenous, genetic and exogenous factors may affect barrier characteristics. The present chapter introduces the theory for barrier penetration (Fick's law), and describes and discusses different methods for measuring the kinetics of percutaneous penetration of chemicals, including in vitro methods (static and flow-through diffusion cells) as well as in vivo methods (microdialysis and microperfusion). Then follows a discussion with examples of how different characteristics of the skin (age, site and integrity) and of the penetrants (size, solubility, ionization, logPow and vehicles) affect the kinetics of percutaneous penetration. Finally, a short discussion of the advantages and challenges of each method is provided, which will hopefully allow the reader to improve decision making and treatment planning, as well as the evaluation of experimental studies of percutaneous penetration of chemicals. PMID- 26844903 TI - Treatments Improving Skin Barrier Function. AB - Moisturizers affect the stratum corneum architecture and barrier homeostasis, i.e. topically applied ingredients are not as inert to the skin as one might expect. A number of different mechanisms behind the barrier-influencing effects of moisturizers have been suggested, such as simple deposition of lipid material outside the skin. Ingredients in the moisturizers may also change the lamellar organization and the packing of the lipid matrix and thereby skin permeability. Topically applied substances may also penetrate deeper into the skin and interfere with the production of barrier lipids and the maturation of corneocytes. Furthermore, moisturizing creams may influence the desquamatory proteases and alter the thickness of the stratum corneum. PMID- 26844904 TI - Standards for the Protection of Skin Barrier Function. AB - The skin is a vital organ, and through our skin we are in close contact with the entire environment. If we lose our skin we lose our life. The barrier function of the skin is mainly driven by the sophisticated epidermis in close relationship with the dermis. The epidermal epithelium is a mechanically, chemically, biologically and immunologically active barrier submitted to continuous turnover. The barrier function of the skin needs to be protected and restored. Its own physiology allows its recovery, but many times this is not sufficient. This chapter is focused on the standards to restore, treat and prevent barrier function disruption. These standards were developed from a scientific, academic and clinical point of view. There is a lack of standardized administrative recommendations. Still, there is a walk to do that will help to reduce the social and economic burden of diseases characterized by an abnormal skin barrier function. PMID- 26844905 TI - The Role of the Skin Barrier in Occupational Skin Diseases. AB - Occupational skin diseases (OSDs) are the second most common occupational diseases worldwide. Occupational contact dermatitis (OCD) is the most frequent OSD, and comprises irritant contact dermatitis (ICD), allergic contact dermatitis (ACD), contact urticaria and protein contact dermatitis. There are many endogenous and exogenous factors which affect the development of OCD, including age, sex, ethnicity, atopic skin diathesis, certain occupations and environmental factors. One of the most important contributing causes is skin barrier dysfunction. The skin provides a first-line defense from environmental assaults and incorporates physical, chemical and biological protection. Skin barrier disturbance plays a crucial role in various skin diseases such as atopic dermatitis (AD), ichthyosis, ICD and ACD. Genetic factors, such as filaggrin gene (FLG) mutations, and external factors, such as skin irritants interfering with stratum corneum structure and composition, may lead to abnormalities in skin barrier function and increased vulnerability to skin diseases. FLG encodes the cornified envelope protein, filaggrin, which is involved in skin barrier function. FLG mutation is associated with the development of OCD. High-risk occupations for OCD include health care workers, hairdressers and construction workers. There are often multiple contributing causes to OCD, as workers are exposed to both irritants and allergens. AD is also associated with skin barrier disruption and plays an important role in OCD. ICD often precedes and facilitates the development of ACD, with impairment of the skin barrier contributing to the concurrence of ICD and ACD in many workers with OCD. PMID- 26844906 TI - Wet Work and Barrier Function. AB - Wet work defined as unprotected exposure to humid environments/water; high frequencies of hand washing procedures or prolonged glove occlusion is believed to cause irritant contact dermatitis in a variety of occupations. This review considers the recent studies on wet-work exposure and focuses on its influence on barrier function. There are different methods to study the effect of wet work on barrier function. On the one hand, occupational cohorts at risk can be monitored prospectively by skin bioengineering technology and clinical visual scoring systems; on the other hand, experimental test procedures with defined application of water, occlusion and detergents are performed in healthy volunteers. Both epidemiological studies and the results of experimental procedures are compared and discussed. A variety of epidemiological studies analyze occupational cohorts at risk. The measurement of transepidermal water loss, an indicator of the integrity of the epidermal barrier, and clinical inspection of the skin have shown that especially the frequencies of hand washing and water contact/contact to aqueous mixtures seem to be the main factors for the occurrence of barrier alterations. On the other hand, in a single cross-sectional study, prolonged glove wearing (e.g. occlusion for 6 h per shift in clean-room workers) without exposure to additional hazardous substances seemed not to affect the skin negatively. But regarding the effect of occlusion, there is experimental evidence that previously occluded skin challenged with sodium lauryl sulfate leads to an increased susceptibility to the irritant with an aggravation of the irritant reaction. These findings might have relevance for the real-life situation in so far as after occupational glove wearing, the skin is more susceptible to potential hazards to the skin even during leisure hours. PMID- 26844907 TI - Saving the Barrier by Prevention. AB - One third of all occupation-related diseases are diseases of the skin, and in most of these cases the skin barrier is involved. Professions such as metalworkers, hairdressers, and health care and construction workers are mainly affected. Among them, contact dermatitis is the leading skin disease. It usually presents as hand eczema caused by or leading to impaired barrier function. All this significantly impacts the function of the hands, reduces the ability to work and especially impairs the patient's quality of life. Diagnostics and therapy are of great importance; in addition, prevention programs are meanwhile an important mainstay of the overall therapeutic concept. They comprise measures of secondary (outpatient) and tertiary (inpatient) prevention. Secondary prevention measures include occupation-tailored teaching and prevention programs, and the dermatologist's examination and report. In severe cases or if therapy is not successful in the long term, or if the diagnosis is not clear, measures of tertiary prevention may come into action. They are offered as an inpatient treatment and prevention program. The aims are prevention of the job loss, but especially to reach a long-term healing up and getting back to normal occupational and leisure life in the sense of attaining full quality of life. During the last years, research in Germany has shown that the different measures of prevention in occupational dermatology are very effective. This integrated concept of an in-/outpatient disease management reveals remarkable pertinent efficacy for patients with severe occupational dermatoses in at-risk professions. PMID- 26844908 TI - Simultaneous immunoassay of phosphorylated proteins based on apoferritin templated metallic phosphates as voltammetrically distinguishable signal reporters. AB - A novel electrochemical immunosensor has been developed to detect phosphorylated proteins, phospho-p53(15) and phospho-p53(392), simultaneously. Different apoferritin templated metal phosphates were used as distinguishable signal reporters (apoferritin templated cadmium phosphates (ATCP) and apoferritin templated lead phosphates (ATLP)) to enhance the detection sensitivity. Here, magnetic Fe3O4 nanoparticles functionalized phospho-p53(15) capture antibody (MP p53(15)c-Ab) and phospho-p53(392) capture antibody (MP-p53(392)c-Ab), respectively, were used to specifically capture phospho-p53(15) and phospho p53(392) antigens, followed by immunorecognition with p53(15) detection antibody (p53(15)d-Ab) and p53(392) detection antibody (p53(392)d-Ab) to form sandwich like immunocomplexes. SiO2@Au nanocomposites served as nanocarriers for co immobilization of both d-Ab and signal reporters (ATCP/SiO2@Au/p53(15)d-Ab, ATLP/SiO2@Au/p53(392)d-Ab), which greatly amplified the detection signal. The distinguished current responses were achieved by electrochemical detection of cadmium ions and lead ions with square wave voltammetry (SWV) after dissolution with acid. The proposed immunoassay exhibited high sensitivity and selectivity for the detection of phospho-p53(15) and phospho-p53(392) simultaneously. The linear relationships between electrochemical responses and the concentrations of phospho-p53(15) and phospho-p53(392) were obtained in the range of 0.1-20 ng/mL and 0.05-20 ng/mL, respectively. The detection limits were 0.05 and 0.02 ng/mL (S/N=3), respectively. This strategy provides a new platform for simultaneous immunoassay of multiple protein biomarkers. PMID- 26844909 TI - Talking past each other: Interviewer and child verbal exchanges in forensic interviews. AB - We used sequential analysis to examine the relationship between interviewer question types, child responsiveness, and subsequent interviewer prompting in 103 forensic interviews investigating sexual abuse allegations with children (6-16 years old). Broad open-ended prompts were more likely to elicit responses (83%) than nonresponses (17%) from children, but nonresponding was more highly associated with this type of prompt than expected by chance. Closed-ended prompts elicited more responses (96%) than nonresponses (4%) from children, and these prompts were more likely to elicit a response than expected by chance. Interviewers did not consistently engage in "pairing" and generally did not alter their questioning style in response to children's behavior. As expected, more frequent use of pairing was positively associated with open-ended prompting and negatively associated with focused prompting. Similarly, children's responding style remained consistent irrespective of the questions posed to them. Thus, much of the interviews seemed to be composed of interviewers and children talking past one another. Interviewing training and supervision of interviewing practice may benefit by including a focus on the pairing principle. PMID- 26844910 TI - The habitual female offender inside: How psychopathic traits predict chronic prison violence. AB - Psychopathy is considered one of the best predictors of violence and prison misconducts and is arguably an important clinical construct in the correctional setting. However, we tested whether psychopathy can be used to predict misconducts in prison environments for women as has been done for men. To date, few studies exist that examine and validate this association in female offender samples. The present study included 182 ethnically diverse female offenders. The aim was to prospectively predict violent and nonviolent misconducts over a 9 month period using official records of prior violent criminal history (e.g., homicide, manslaughter, assault), and self-report measures of psychopathy, impulsivity, and empathy. Using negative binomial regression, we found that past violent criminal history, and callous and antisocial psychopathic traits were predictors of violent misconducts, whereas antisocial psychopathic traits and impulsivity best predicted nonviolent misconducts. Although empathy was negatively associated with psychopathy it was not a significant predictor of violent or nonviolent misconducts. Statistical models, which included impulsivity, were considered the most parsimonious at predicting misconducts. Our findings demonstrate how risk-factors found to be reliable in male offender samples, such as psychopathic traits, impulsivity, and past violent criminal history, generalize to female offenders for predicting nonviolent and violent misconducts. One notable difference is the importance of callous psychopathic traits when predicting chronic violent misconducts by female offenders. In sum, there are more similarities in psychopathy and impulsivity than differences in the prediction of misconducts among men and women. (PsycINFO Database Record PMID- 26844911 TI - Boldness and its relation to psychopathic personality: Prototypicality analyses among forensic mental health, criminal justice, and layperson raters. AB - Research on psychopathic personality has been dominated by a focus on criminality and social deviance, but some theoretical models argue that certain putatively adaptive features are important components of this construct. In 3 samples (forensic mental health practitioners, probation officers and a layperson community sample), we investigated adaptive traits as conceptualized in the Triarchic model of psychopathy (Patrick et al., 2009), specifically the relevance of boldness to construals of psychopathic personality. Participants completed prototypicality ratings of psychopathic traits, including 3 items created to tap components of boldness (Socially bold, Adventurous, Emotionally stable), and they also rated a series of attitudinal statements (e.g., perceived correlates of being psychopathic, moral judgments about psychopaths). The composite Boldness scale was rated as moderately to highly prototypical among forensic mental health practitioners and probation officers and positively associated with other theoretically relevant domains of psychopathy. Across samples, higher composite Boldness ratings predicted greater endorsement of adaptive traits (e.g., social skills) as characteristic of psychopathy. For the individual items, Socially bold was rated as highly prototypical and was associated with theoretically relevant correlates. Adventurous also was seen as prototypical, though to a lesser degree. Only forensic mental health practitioners endorsed Emotionally stable as characteristic of psychopathy. Our results provide partial support for the contention that the boldness concept is viewed as an important component of psychopathy, particularly among professionals who work directly with offender populations. (PsycINFO Database Record PMID- 26844912 TI - Experienced and novice officers' generalized communication suspicion and veracity judgments. AB - Deception detection research has shown that police officers are less truth-biased and make their veracity judgments with greater confidence than do nonofficers. Here we examined nonofficers, novice officers, and experienced officers' response bias, confidence, and generalized communicative suspicion. In Experiment 1, novice officers aligned with nonofficers in terms of both generalized communicative suspicion scores and confidence, with both these groups scoring lower than experienced officers. Generalized communicative suspicion scores and veracity judgments were not significantly related for either sample. However, novice officers aligned with experienced officers in terms of judgments: both police groups were lie-biased, whereas nonofficers were truth-biased. These findings suggest that unlike experienced officers, who have embraced the police culture to a greater degree, novice officers are not dispositionally suspicious (generalized communicative suspicion); however, they are able to mirror the prototypical police behavior (deception judgments) in police-related contexts. Experiment 2 supported these notions. PMID- 26844913 TI - Quality of life in relation to future mental health problems and offending: Testing the good lives model among detained girls. AB - Detained girls bear high levels of criminal behavior and mental health problems that are likely to persist into young adulthood. Research with these girls began primarily from a risk management perspective, whereas a strength-based empowering perspective may increase knowledge that could improve rehabilitation. This study examines detained girls' quality of life (QoL) in relation to future mental health problems and offending, thereby testing the strength-based good lives model of offender rehabilitation (GLM). At baseline, 95 girls (Mage = 16.25) completed the World Health Organization QoL instrument to assess their QoL prior to detention in the domains of physical health, psychological health, social relationships, and environment. Six months after discharge, mental health problems and offending were assessed by self-report measures. Structural equation models were conducted to test GLM's proposed (in)direct pathways from QoL (via mental health problems) toward offending. Although we could not find support for GLM's direct negative pathway from QoL to offending, our findings did provide support for GLM's indirect negative pathway via mental health problems to future offending. In addition, we found a direct positive pathway from detained girls' satisfaction with their social relationships to offending after discharge. The current findings support the potential relevance of addressing detained girls' QoL, pursuing the development of new skills, and supporting them to build constructive social contacts. Our findings, however, also show that clinicians should not only focus on strengths but that detecting and modifying mental health problems in this vulnerable group is also warranted. (PsycINFO Database Record PMID- 26844914 TI - Estimated Glomerular Filtration Rate: Fit for What Purpose? AB - There is important nosologic utility in staging chronic kidney disease (CKD) based on estimates of glomerular filtration rate (GFR). These equations have been optimized for estimating GFR at a single point in time. Risk assessment models used for prognosis of specified outcome events have commonly incorporated estimated GFR (eGFR), but the validity of this approach has not been evaluated. The current objective is to evaluate the risk of all-cause mortality over a 10 year follow-up period with multivariable-adjusted Cox regression analysis, comparing CKD stages based on eGFR to Cockcroft-Gault estimated creatinine clearance (eCrCl). There were significant differences between Stage 3A and Stage 3B-5 hazard ratios for all-cause mortality (p = 0.003) using eCrCl categories, but not for the same eGFR categories (p = 0.241). Discrimination analysis showed that a clinically significant difference (relative integrated discrimination improvement 778.6%; p = 0.001) was observed between the 2 models for the age strata <=64. While eGFR is more precise and accurate than the Cockcroft Gault equation for estimating measured GFR at a single point in time, eGFR does not perform as well as eCrCl for assessing risk of all-cause mortality over 10-year follow-up intervals. PMID- 26844916 TI - Age-Dependent Impact of Medication Underuse and Strategies for Improvement. AB - BACKGROUND: Medication underuse is common in aging populations and, because of the growing risk for competing deaths, the benefit of preventive medicines gradually vanishes with advancing age, thus limiting their success. OBJECTIVE: To estimate the optimum time of initiation of the secondary prevention of cardiovascular events, we examined the impact of appropriate pharmacotherapy for different starting ages at which it is implemented. METHODS: In the competing risk framework, we obtained the population's life course from life tables, combined it with effect estimates quantifying the real-world effectiveness of secondary prevention, and compared the outcome of patients not receiving appropriate treatment (underuse) with those receiving preventive medicines that have demonstrated a reduction in the transition to serious cardiovascular events (START criteria). Starting at the age of 55 years, the population proportions of the distinct states of the framework were calculated for each year of chronological age in subgroups of appropriate treatment and underuse. These proportions were used over a follow-up period to estimate measures of treatment effectiveness and risks of underuse. RESULTS: Despite increasing relative effectiveness with advancing age, benefits measured by patient-relevant endpoints, such as life years gained (LYG) or gained quality-adjusted life years (QALYs), markedly dropped after the starting age of 75 years, but even at an initiation age of 85 years, QALYs gained exceeded 1 year. CONCLUSION: Interventions targeting medication underuse may achieve considerable benefits at any stage of later life, while the benefit is probably largest if appropriate treatment is started before 75 years. PMID- 26844915 TI - Beneficial effects of nilotinib, tyrosine kinase inhibitor on cyclosporine-A induced renal damage in rats. AB - Nilotinib is a known tyrosine kinase inhibitor that has been approved for treatment of leukemia. The possible protective effect of nilotinib on cyclosporine A-induced nephropathy was investigated in this study and the possible underlying mechanism was explored. Nilotinib (25mg/kg, orally) and cyclosporine A (15 mg/kg/day, subcutaneous) were given to male SD rats for 28 days. Cyclosporine A alone was found to significantly increase serum creatinine, blood urea nitrogen, lactate dehydrogenase, urinary micrototal protein, renal thiobarbituric acid reactive substance, Bax, cytosol cytochrome c release and nuclear factor kappa B activation. Moreover, cyclosporine A significantly reduced serum albumin, creatinine clearance, urinary total antioxidant, superoxide dismutase, glutathione and Bcl2 protein levels. Pathological results showed that in the model group; there was an obvious shrinkage and congestion of the glomeruli and widening of urinary spaces of renal corpuscles, in addition to marked renal tubular injury and fibrosis, while in the group pretreated with nilotinib all measured serum, renal and pathological changes were significantly reduced. This protective effect of nilotinib is linked to the enhanced antioxidant status and reduced inflammation and apoptosis induced by cyclosporine A. PMID- 26844917 TI - Massively parallel sequencing of the entire control region and targeted coding region SNPs of degraded mtDNA using a simplified library preparation method. AB - The application of next-generation sequencing (NGS) to forensic genetics is being explored by an increasing number of laboratories because of the potential of high throughput sequencing for recovering genetic information from multiple markers and multiple individuals in a single run. A cumbersome and technically challenging library construction process is required for NGS. In this study, we propose a simplified library preparation method for mitochondrial DNA (mtDNA) analysis that involves two rounds of PCR amplification. In the first-round of multiplex PCR, six fragments covering the entire mtDNA control region and 22 fragments covering interspersed single nucleotide polymorphisms (SNPs) in the coding region that can be used to determine global haplogroups and East Asian haplogroups were amplified using template-specific primers with read sequences. In the following step, indices and platform-specific sequences for the MiSeq((r)) system (Illumina) were added by PCR. The barcoded library produced using this simplified workflow was successfully sequenced on the MiSeq system using the MiSeq Reagent Nano Kit v2. A total of 0.4 GB of sequences, 80.6% with base quality of >Q30, were obtained from 12 degraded DNA samples and mapped to the revised Cambridge Reference Sequence (rCRS). A relatively even read count was obtained for all amplicons, with an average coverage of 5200 * and a less than three-fold read count difference between amplicons per sample. Control region sequences were successfully determined, and all samples were assigned to the relevant haplogroups. In addition, enhanced discrimination was observed by adding coding region SNPs to the control region in in silico analysis. Because the developed multiplex PCR system amplifies small-sized amplicons (<250 bp), NGS analysis using the library preparation method described here allows mtDNA analysis using highly degraded DNA samples. PMID- 26844918 TI - A molecular exploration of human DNA/RNA co-extracted from the palmar surface of the hands and fingers. AB - "Touch DNA" refers to the DNA that is left behind when a person touches or comes into contact with an item. However, the source of touch DNA is still debated and the large variability in DNA yield from casework samples suggests that, besides skin, various body fluids can be transferred through contact. Another important issue concerning touch DNA is the possible occurrence of secondary transfer, but the data published in the literature in relation to the background levels of foreign DNA present on the hand surfaces of the general population are very limited. As the present study aimed at better understanding the nature and characteristics of touch DNA, samples were collected from the palmar surface of the hands and fingers ("PHF" samples) of 30 male and 30 female donors by tape lifting/swabbing and subjected to DNA/RNA co-extraction. Multiplex mRNA profiling showed that cellular material different from skin could be observed in 15% of the PHF samples. The total amount of DNA recovered from these samples (median 5.1 ng) was significantly higher than that obtained from samples containing skin cells only (median 1.6 ng). The integrity of the DNA isolated from the donors' hands and fingers as well as the prevalence of DNA mixtures were evaluated by STR typing and compared with reference STR profiles from buccal swabs. DNA integrity appeared significantly higher in the male rather than in the female subsample, as the average percentage of the donors' alleles effectively detected in PHF profiles was 75.1% and 60.1%, respectively. The prevalence of mixtures with a foreign DNA contribution >=20% was 19.2% (30.0% in the female PHF samples and 8.3% in the male PHF samples). The obtained results support the hypothesis that transfer of cellular material different from skin may underlie the occasional recovery of quality STR profiles from handled items. These results also suggest that gender may represent an important factor influencing the propensity of individuals to carry and transfer DNA through hand contact, possibly because of the differences in personal and hygiene habits between males and females. PMID- 26844919 TI - Massively parallel sequencing of forensic STRs: Considerations of the DNA commission of the International Society for Forensic Genetics (ISFG) on minimal nomenclature requirements. AB - The DNA Commission of the International Society for Forensic Genetics (ISFG) is reviewing factors that need to be considered ahead of the adoption by the forensic community of short tandem repeat (STR) genotyping by massively parallel sequencing (MPS) technologies. MPS produces sequence data that provide a precise description of the repeat allele structure of a STR marker and variants that may reside in the flanking areas of the repeat region. When a STR contains a complex arrangement of repeat motifs, the level of genetic polymorphism revealed by the sequence data can increase substantially. As repeat structures can be complex and include substitutions, insertions, deletions, variable tandem repeat arrangements of multiple nucleotide motifs, and flanking region SNPs, established capillary electrophoresis (CE) allele descriptions must be supplemented by a new system of STR allele nomenclature, which retains backward compatibility with the CE data that currently populate national DNA databases and that will continue to be produced for the coming years. Thus, there is a pressing need to produce a standardized framework for describing complex sequences that enable comparison with currently used repeat allele nomenclature derived from conventional CE systems. It is important to discern three levels of information in hierarchical order (i) the sequence, (ii) the alignment, and (iii) the nomenclature of STR sequence data. We propose a sequence (text) string format the minimal requirement of data storage that laboratories should follow when adopting MPS of STRs. We further discuss the variant annotation and sequence comparison framework necessary to maintain compatibility among established and future data. This system must be easy to use and interpret by the DNA specialist, based on a universally accessible genome assembly, and in place before the uptake of MPS by the general forensic community starts to generate sequence data on a large scale. While the established nomenclature for CE-based STR analysis will remain unchanged in the future, the nomenclature of sequence-based STR genotypes will need to follow updated rules and be generated by expert systems that translate MPS sequences to match CE conventions in order to guarantee compatibility between the different generations of STR data. PMID- 26844920 TI - Clinical course and potential complications of small ventricular septal defects in adulthood: Late development of left ventricular dysfunction justifies lifelong care. AB - BACKGROUND: Patients with small ventricular septal defects (VSDs) are thought to have excellent long-term survival, although complications may not be uncommon. METHODS: We identified all patients aged >= 16 years with native isolated VSD between January 2000 and September 2013. Clinical outcomes were retrospectively reviewed. Transthoracic echocardiograms performed within 2 years of last assessment were reviewed for hemodynamic sequelae. RESULTS: Two-hundred-and thirty-one patients, 100 (43%) male, mean age at last follow-up 34 +/- 13 years were studied. During the recorded period there were no deaths. The majority (224/231; 97%) were asymptomatic. Documented arrhythmias occurred in 7 patients (3%), double-chamber right ventricle (DCRV) in 29 (13%), more than mild aortic regurgitation in 6 (3%) and infective endocarditis in 24 (10%) patients. Surgery due to complications associated with VSD was performed in 26 (11%) patients at a median age of 27.6 years (IQR: 16.1-38.7) due to DCRV (n=17, 65%), infective endocarditis (n=6, 23%), progression of left-right shunt (n=2, 8%) and aortic regurgitation (n=1, 4%). At most recent echocardiography (n=164), 10 (6%), had reduced LVEF, 34 (21%) had increased LVEDD and 17 (10%) had LVESD >4.0 cm. Thirty two patients (25%) with normal LV dimensions had LA enlargement suggesting LV diastolic dysfunction. CONCLUSIONS: We report a non-negligible incidence of major complications or clinical events during late follow-up of adult patients with restrictive VSDs. Furthermore, we show co-existing LV dysfunction, systolic or diastolic in a subset of patients. Indication for VSD closure in childhood may be recognized, whereas lifelong follow-up for adult with restrictive VSDs is clearly warranted. PMID- 26844921 TI - Prime time for 25-hydroxycholestrol treatment against inflammation and viral infections? PMID- 26844922 TI - Pulmonary and hepatic injury after sub-chronic exposure to sublethal doses of microcystin-LR. AB - We had previously shown that microcystin-LR (MCLR) could induce lung and liver inflammation after acute exposure. The biological outcomes following prolonged exposure to MCLR, although more frequent, are still poorly understood. Thus, we aimed to verify whether repeated doses of MCLR could damage lung and liver and evaluate the dose-dependence of the results. Male Swiss mice received 10 intraperitoneal injections (i.p.) of distilled water (60 MUL, CTRL) or different doses of MCLR (5 MUg/kg, TOX5), 10 MUg/kg (TOX10), 15 MUg/kg (TOX15) and 20 MUg/kg (TOX20) every other day. On the tenth injection respiratory mechanics (lung resistive and viscoelastic/inhomogeneous pressures, static elastance, and viscoelastic component of elastance) was measured. Lungs and liver were prepared for histology (morphometry and cellularity) and inflammatory mediators (KC and MIP-2) determination. All mechanical parameters and alveolar collapse were significantly higher in TOX5, 10, 15 and 20 than CTRL, but did not differ among them. Lung inflammatory cell content increased dose-dependently in all TOX groups in relation to CTRL, being TOX20 the largest. The production of KC was increased in lung and liver homogenates. MIP-2 increased in the liver of all TOX groups, but in lung homogenates it was significantly higher only in TOX20 group. All TOX mice livers showed steatosis, necrosis, inflammatory foci and a high degree of binucleated hepatocytes. In conclusion, sub-chronic exposure to MCLR damaged lung and liver in all doses, with a more important lung inflammation in TOX20 group. PMID- 26844923 TI - Ethnomedicinal uses, phytochemistry and pharmacological properties of the genus Boerhavia. AB - ETHNOPHARMACOLOGICAL RELEVANCE: The genus Boerhavia is widely distributed in tropical, subtropical and temperate regions of the world including Mexico, America, Africa, Asia, Indian Ocean Islands, Pacific Islands and Australia. The genus Boerhavia is extensively used by local peoples and medicinal practitioners for treatments of hepatitis, urinary disorders, gastro intestinal diseases, inflammations, skin problems, infectious diseases and asthma. Present review focused on traditional uses, phytochemistry, pharmacology and toxicology of Boerhavia genus to support potential scope for advance ethnopharmacological study. MATERIALS AND METHODS: Information on the Boerhavia species was collected from classical books on medicinal plants, pharmacopoeias and scientific databases like PubMed, Scopus, GoogleScholar, Web of Science and others. Also scientific literatures based on ethnomedicinal surveys, Ph.D. and M.Sc. dissertations, published papers from Elsevier, Taylor and Francis, Springer, ACS as well as Wiley publishers and reports by government bodies and documentations were assessed. RESULTS: A total of 180 compounds from Boerhavia genus were isolated of which B. diffusa alone shared around 131 compounds and for most of which it is currently an exclusive source. In the genus, phenolic glycosides and flavonoids contribute approximately 97 compounds. These includes eupalitin, rotenoids like boeravinones, coccineons, alkaloid i.e. betanin and punarnavine etc., showing vital pharmaceutical activities such as anticancer, anti-inflammatory, antioxidant and immunomodulatory. CONCLUSION: Boerhavia is an important genus with wide range of medicinal uses. However, most of the available scientific literatures have lacked relevant doses, duration and positive controls for examining bioefficacy of extracts and its active compounds. In some studies, taxonomic errors were encountered. Moreover, there is need for accurate methods in testing the safety and ethnomedicinal validity of Boerhavia species. PMID- 26844924 TI - Mechanical and Transport Properties of Poly(propylene-co-1-heptene) Copolymers and Their Dependence on Monoclinic and/or Mesomorphic Polymorphs. AB - Poly(propylene-co-1-heptene) copolymers have been evaluated in a wide 1-heptene content range. Two different polymorphs can be observed in this interval under the processing conditions imposed: monoclinic crystallites and mesomorphic entities. The unique presence of one or the other lattice at specific content or the coexistence of both of them at the intermediate composition interval is a key factor affecting some of the exhibited properties. The influence is observed in characteristics mainly dependent on either crystalline structure, like rigidity, or the amorphous regions, as location and intensity of glass transition. To get a deeper understanding, the transition from mesophase to monoclinic crystallites has also been studied by DSC and by WAXS and SAXS experiments using synchrotron radiation. It is observed that this transformation is only partial and just involves one-third of the initial ordered mesomorphic entities. Permeability to different gases is mainly dependent on amorphous content and hindrance that monoclinic or mesomorphic entities impose on those disordered regions. PMID- 26844925 TI - Evaluation of different strategies to mask boar taint in cooked sausage. AB - The use of smoking and/or spices was evaluated for their ability to mask boar taint in frankfurters manufactured from entire pigs with high levels of androstenone. Five frankfurter types were considered: control, smoked, flavouring+smoked, spicy and spicy+smoked. A trained panel in androstenone perception carried out a sensory profile on the different sausages. The highest scores for androstenone perception (odour, flavour and aftertaste) were found in frankfurters that included no masking strategy which indicated the effectiveness of the evaluated strategies. Regarding masking strategies, the contribution of spices and smoking to sensory perception of frankfurters was detected by the panellists. Smoking was the best strategy to mask androstenone odour, while the use of spices masked androstenone odour to a greater extent than androstenone flavour. Only the combined use of spices and smoking was able to eliminate the perception of androstenone. The application of this strategy in frankfurters could be an alternative in the commercialization of entire pigs. PMID- 26844926 TI - Allergen-induced Changes in Bone Marrow and Airway Dendritic Cells in Subjects with Asthma. AB - RATIONALE: Dendritic cells (DCs) are antigen-presenting cells essential for the initiation of T-cell responses. Allergen inhalation increases the number of airway DCs and the release of epithelial-derived cytokines, such as IL-33 and thymic stromal lymphopoietin (TSLP), that activate DCs. OBJECTIVES: To examine the effects of inhaled allergen on bone marrow production of DCs and their trafficking into the airways in subjects with allergic asthma, and to examine IL 33 and TSPL receptor expression on DCs. METHODS: Bone marrow, peripheral blood, bronchoalveolar lavage (BAL), and bronchial biopsies were obtained before and after inhalation of diluent and allergen from subjects with asthma that develop allergen-induced dual responses. Classical DCs (cDCs) were cultured from bone marrow CD34(+) cells. cDC1s, cDC2s, and plasmacytoid DCs were measured in bone marrow aspirates, peripheral blood, and BAL by flow cytometry, and cDCs were quantified in bronchial biopsies by immunofluorescence staining. MEASUREMENTS AND MAIN RESULTS: Inhaled allergen increased the number of cDCs grown from bone marrow progenitors, and cDCs and plasmacytoid DCs in bone marrow aspirates 24 hours after allergen. Allergen also increased the expression of the TSLP receptor, but not the IL-33 receptor, on bone marrow DCs. Finally, inhaled allergen increased the percentage of cDC1s and cDC2s in BAL but only cDC2s in bronchial tissues. CONCLUSIONS: Inhaled allergen increases DCs in bone marrow and trafficking of DCs into the airway, which is associated with the development airway inflammation in subjects with allergic asthma. Inhaled allergen challenge also increases expression of TSLP, but not IL-33, receptors on bone marrow DCs. PMID- 26844928 TI - Synthesis and Aggregation Behavior of Chiral Naphthoquinoline Petroporphyrin Asphaltene Model Compounds. AB - The synthesis of structurally relevant compounds that model the chemical behavior and supramolecular aggregation of the asphaltenes, the most polar and metal-rich fraction of heavy petroleum, has been extended to include fusions of important petroleum biomarkers. The synthetic protocol features a multicomponent reaction to form a dyad composed of a fused steroidal naphthoquinoline, followed by a pyrrole cyclocondensation reaction to incorporate the dyad into a chiral triad containing a NiII -porphyrin substituent. This synthetic protocol has been used to prepare large molecules that represent both "continental" and "archipelago" models of asphaltene composition. The steroid-naphthoquinoline-porphyrin triads have been studied by UV/Vis and circular dichroism (CD) spectroscopies, and the results suggest that the naphthoquinoline core, a tetrahydro[4]helicene, adopts a helical conformation, producing a CD signal electronically related to the characteristic Soret absorption band of the porphyrin subunit. Finally, supramolecular aspects of asphaltene aggregation have been examined on a molecular level through analysis of axial coordination of pyridine to the Ni porphyrin. The relative affinity of pyridine for binding to the Ni center of the porphyrin is evaluated by comparing binding propensities in a series of sterically differentiated substituted porphyrins. PMID- 26844927 TI - Primary visual cortex shows laminar-specific and balanced circuit organization of excitatory and inhibitory synaptic connectivity. AB - KEY POINTS: Using functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory neurons in layers 2/3-6 of the mouse visual cortex (V1). Laminar specific synaptic wiring diagrams of excitatory neurons were constructed on the basis of circuit mapping. The present study reveals that that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks in V1. ABSTRACT: In the mammalian neocortex, excitatory neurons provide excitation in both columnar and laminar dimensions, which is modulated further by inhibitory neurons. However, our understanding of intracortical excitatory and inhibitory synaptic inputs in relation to principal excitatory neurons remains incomplete, and it is unclear how local excitatory and inhibitory synaptic connections to excitatory neurons are spatially organized on a layer-by-layer basis. In the present study, we combined whole cell recordings with laser scanning photostimulation via glutamate uncaging to map excitatory and inhibitory synaptic inputs to single excitatory neurons throughout cortical layers 2/3-6 in the mouse primary visual cortex (V1). We find that synaptic input sources of excitatory neurons span the radial columns of laminar microcircuits, and excitatory neurons in different V1 laminae exhibit distinct patterns of layer specific organization of excitatory inputs. Remarkably, the spatial extent of inhibitory inputs of excitatory neurons for a given layer closely mirrors that of their excitatory input sources, indicating that excitatory and inhibitory synaptic connectivity is spatially balanced across excitatory neuronal networks. Strong interlaminar inhibitory inputs are found, particularly for excitatory neurons in layers 2/3 and 5. This differs from earlier studies reporting that inhibitory cortical connections to excitatory neurons are generally localized within the same cortical layer. On the basis of the functional mapping assays, we conducted a quantitative assessment of both excitatory and inhibitory synaptic laminar connections to excitatory cells at single cell resolution, establishing precise layer-by-layer synaptic wiring diagrams of excitatory neurons in the visual cortex. PMID- 26844929 TI - Fluorescent Rhodamines and Fluorogenic Carbopyronines for Super-Resolution STED Microscopy in Living Cells. AB - A range of bright and photostable rhodamines and carbopyronines with absorption maxima in the range of lambda=500-630 nm were prepared, and enabled the specific labeling of cytoskeletal filaments using HaloTag technology followed by staining with 1 MUm solutions of the dye-ligand conjugates. The synthesis, photophysical parameters, fluorogenic behavior, and structure-property relationships of the new dyes are discussed. Light microscopy with stimulated emission depletion (STED) provided one- and two-color images of living cells with an optical resolution of 40-60 nm. PMID- 26844930 TI - Structural Re-engineering of the alpha-Helix Mimetic JY-1-106 into Small Molecules: Disruption of the Mcl-1-Bak-BH3 Protein-Protein Interaction with 2,6 Di-Substituted Nicotinates. AB - The disruption of aberrant protein-protein interactions (PPIs) with synthetic agents remains a challenging goal in contemporary medicinal chemistry but some progress has been made. One such dysregulated PPI is that between the anti apoptotic Bcl-2 proteins, including myeloid cell leukemia-1 (Mcl-1), and the alpha-helical Bcl-2 homology-3 (BH3) domains of its pro-apoptotic counterparts, such as Bak. Herein, we describe the discovery of small-molecule inhibitors of the Mcl-1 oncoprotein based on a novel chemotype. Particularly, re-engineering of our alpha-helix mimetic JY-1-106 into 2,6-di-substituted nicotinates afforded inhibitors of comparable potencies but with significantly decreased molecular weights. The most potent inhibitor 2-(benzyloxy)-6-(4-chloro-3,5 dimethylphenoxy)nicotinic acid (1 r: Ki =2.90 MUm) likely binds in the p2 pocket of Mcl-1 and engages R263 in a salt bridge through its carboxylic acid, as supported by 2D (1) H-(15) N HSQC NMR data. Significantly, inhibitors were easily accessed in just four steps, which will facilitate future optimization efforts. PMID- 26844931 TI - Ultra high performance liquid chromatography with mass spectrometry for the rapid analysis and global characterization of multiple constituents from Zibu Piyin Recipe. AB - Zibu Piyin Recipe is a traditional Chinese medicine that has been used for the clinical treatment of memory loss in China. However, the chemical components have not been thoroughly studied so far. To quickly identify the chemical components and understand the chemical profiles related to cognition improvement activity, ultra high performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry has been applied. The analysis was performed on an Agilent 1290 ultra-high performance liquid chromatography system with a Poroshell 120 EC-C18 column (3.0 * 150 mm, 2.7 MUm) using gradient elution. Using the optimized method, 155 chemical components in Zibu Piyin Recipe were tentatively identified. Among them, 112 components in negative ion mode, 73 constituents in positive ion mode, and 30 compounds in both modes could be detected. The major components were identified from Red Ginseng, Dan shen Root, White Paeony Root, liquorice root, Radix Polygalae, Tangerine Red Epicarp, Grassleaf Sweetflag Rhizome, Indian Buead, and lotus seed. These results suggest that the established rapid and robust method will be useful for identifying multiple constituents of traditional Chinese medicine prescriptions. This method could provide helpful chemical information for further in vivo pharmacological mechanism research of Zibu Piyin Recipe and new drug development for cognition improvement. PMID- 26844934 TI - The Relationship of Cerebral Vessel Pathology to Brain Microinfarcts. AB - The relationship of cerebral vessel pathology to brain microinfarcts is not fully understood. We examined associations of cerebral vessel pathology with microinfarcts among community-dwelling persons who came to autopsy. Brain specimens were derived from 1,066 deceased subjects (mean age-at-death = 88 years, 65% women) participating in a cohort study of aging. Microinfarcts were classified by number, age and location. Severity of vessel pathologies was graded semi-quantitatively. Almost a third of subjects (n = 300; 28%) had at least one chronic microinfarct, including 128 cortical only, 120 subcortical only, and 47 with both. Moderate-to-severe atherosclerosis was present in 430 (41%) subjects, arteriolosclerosis in 382 (36%), and amyloid angiopathy in 374 (35%). The odds of one or multiple microinfarct(s) was increased for more severe atherosclerosis (OR =1.22; 95%CI: 1.03-1.45), arteriolosclerosis (OR =1.18; 95%CI: 1.02-1.37) and amyloid angiopathy (OR =1.13; 95%CI: 1.00-1.28). Separately, the odds of subcortical microinfarct(s) was increased for atherosclerosis (OR =1.49; 95%CI: 1.20-1.84) and arteriolosclerosis (OR =1.39; 95%CI: 1.16-1.67) but not amyloid angiopathy; whereas the odds of cortical microinfarct(s) was increased for amyloid angiopathy (OR =1.26; 95%CI: 1.09-1.46) only. While cerebral vessel pathologies are associated with microinfarct burden, atherosclerosis and arteriolosclerosis are associated with subcortical microinfarcts, and amyloid angiopathy with cortical microinfarcts. PMID- 26844935 TI - Stair dimension affects knee kinematics and kinetics in patients with good outcome after TKA similarly as in healthy subjects. AB - Joint biomechanics during stair walking may contain important information on functional deficits in patients with orthopaedic conditions but depend on the stair dimension. The goal of this study was to compare knee kinematics and kinetics between patients with good outcome 2 years after total knee arthroplasty (TKA) and age-matched controls during stair ascent and descent at two different stair heights. Principal component analysis was used to detect differences in gait mechanics between 15 patients and 15 controls at different stair conditions. Linear mixed models showed differences in knee kinematic and kinetic patterns (in flexion/extension and abduction/adduction) between stair heights. The knee adduction angle was more affected by stair heights in stair ascending whereas knee adduction moment and knee power were more affected during stair descent. Some stair by height and subject effects were small but not significant. Overall, good outcome after TKA is reflected in close-to-normal knee biomechanics during stair walking. Specific stair configuration must be considered when comparing joint biomechanics between subject groups and studies. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1753-1761, 2016. PMID- 26844936 TI - NCI seeks to speed drug development for pediatric cancers: New initiative aims to help prioritize agents with most potential. PMID- 26844942 TI - Different biological effects of a constant dose for single UVB irradiation with different intensities and exposure times. PMID- 26844943 TI - SU-8-Induced Strong Bonding of Polymer Ligands to Flexible Substrates via in Situ Cross-Linked Reaction for Improved Surface Metallization and Fast Fabrication of High-Quality Flexible Circuits. AB - On account of in situ cross-linked reaction of epoxy SU-8 with poly(4 vinylpyridine) (P4VP) and its strong reactive bonding ability with different pretreated substrates, we developed a simple universal one-step solution-based coating method for fast surface modification of various objects. Through this method, a layer of P4VP molecules with controllable thickness can be tethered tightly onto substrates with the assistance of SU-8. P4VP molecules possess a lot of pyridine ligands to immobilize transitional metal ions that can behave as the catalyst of electroless copper plating for surface metallization while functioning as the adhesion-promoting layer between the substrate and deposited metal. Attributed to interpenetrated entanglement of P4VP molecules and as deposited metal, ultrathick (>7 MUm) strongly adhesive high-quality copper layer can be formed on flexible substrates without any delamination. Then through laser printer to print toner mask, a variety of designed circuits can be easily fabricated on modified flexible PET substrate. PMID- 26844944 TI - Impaired Left Ventricular Reserve in Childhood Cancer Survivors Treated With Anthracycline Therapy. AB - BACKGROUND: Childhood cancer survivors show evidence of diffuse myocardial fibrosis that is related to exercise capacity. The mechanism of reduced exercise tolerance in anthracycline cardiotoxicity remains unclear. We explored the determinants of exercise intolerance by evaluating left ventricular (LV) distensibility and functional reserve. METHODS: Patients (n = 22) and healthy controls (n = 10) underwent two-dimensional echocardiography while supine, upright, and during cycle exercise. LV distensibility was measured as the change in end-diastolic cavity area (EDCA) from supine to the upright position. LV functional reserve was assessed during peak exercise, and measured as the exercise-induced change in systolic circumferential strain rate (SR) and early diastolic SR (EDSR). The peak rate of oxygen consumption was measured by indirect calorimetry. RESULTS: Median age of patients was 16 years (range 8-19) and controls 14 years (range 8-19). Median time since anthracycline therapy was 6 years (range 2-16). Peak oxygen consumption was significantly lower in patients compared to controls (35 ml/kg/min [28-60] vs. 45 ml/kg/min [44-53], P = 0.005). Transitioning from the supine position to the upright position caused a similar reduction in LV EDCA, suggesting similar LV distensibility between patients (-22% [-46 to -4]) and controls (-20% [-46 to -3], P = 0.3). However, during exercise, both systolic SR and EDSR reserve were significantly impaired in patients (?SR: 93% [14-308], ?EDSR: -4.5% [-88 to 121]) compared to controls (?SR: 128% [54 230], P = 0.046; ?EDSR: 74% [22-234], P = 0.02). CONCLUSIONS: Our findings suggest that impaired LV contractility and functional reserve play a role in the reduced exercise capacity in anthracycline cardiotoxicity rather than LV distensibility. PMID- 26844941 TI - Development of 3D Microvascular Networks Within Gelatin Hydrogels Using Thermoresponsive Sacrificial Microfibers. AB - A 3D microvascularized gelatin hydrogel is produced using thermoresponsive sacrificial poly(N-isopropylacrylamide) microfibers. The capillary-like microvascular network allows constant perfusion of media throughout the thick hydrogel, and significantly improves the viability of human neonatal dermal fibroblasts encapsulated within the gel at a high density. PMID- 26844945 TI - Cataract surgery practices and endophthalmitis prophylaxis by New Zealand Ophthalmologists. PMID- 26844946 TI - 6-sulpho LacNAc(+) dendritic cells accumulate in various inflammatory, but not ischaemic conditions of the central nervous system. PMID- 26844948 TI - Incidental detection of familial APP duplication: an unusual reason for a false positive NIPT result of trisomy 21. PMID- 26844947 TI - Preparation of Enantiomerically Pure Perfluorobutanesulfinamide and Its Application to the Asymmetric Synthesis of alpha-Amino Acids. AB - A high yielding and practical two-step synthesis of enantiomerically pure perfluorobutanesulfinamide from Senanayake's 2-aminoindanol-derived sulfinyl transfer reagent was developed and carried out on a multigram scale. Straightforward condensation of this sulfinamide with ethyl glyoxylate provided the N-perfluorobutanesulfinyl imino ester. The utility of this activated N sulfinyl imino ester was demonstrated for reactions that gave either no product or very low yields with the corresponding less electrophilic N-tert butanesulfinyl derivative. Specifically, the Rh(III)-catalyzed C-H bond addition of aromatic compounds to the N-perfluorobutanesulfinyl imino ester provided arylglycines with very high diastereoselectivities for a range of directing groups including pyrrolidine amide, azo, sulfoximine, 1-pyrazole, and 1,2,3 triazole functionalities. Thermal asymmetric aza-Diels-Alder reactions also proceeded in good yields and with high selectivity, including for the substituted dienes (E)-1,3-pentadiene and (2E,4E)-2,4-hexadiene. PMID- 26844949 TI - Tribochemistry of Carbon Films in Oxygen and Humid Environments: Oxidative Wear and Galvanic Corrosion. AB - The effects of oxidation on wear of carbon/steel tribological interfaces were studied. When mechanical wear was small, the oxidation behavior of hydrogenated diamond-like carbon (H-DLC) and stainless steel (SS) sliding interface varied depending on the nature of the oxidizing environment. In dry air or oxygen, both H-DLC and SS wore readily. The wear debris of SS did not form iron oxide in dry air and oxygen. In humid nitrogen, however, the wear of H-DLC diminished with increasing humidity, and the SS surface showed mild wear and iron oxide debris accumulated around the sliding contact region. These results revealed that different tribochemical reactions occur in dry oxygen and humid environments. In the absence of water, oxygen oxidizes the H-DLC surface, making it susceptible to wear, creating debris, and inducing wear on both H-DLC and SS. In contrast, adsorbed water molecules at less than 40% RH act as a molecular lubricant of the oxidized DLC surface, while multiwater layers adsorbed at near-saturation act as electrolyte inducing electrochemical galvanic corrosion reactions on the SS surface. When hydrogen-free amorphous carbon (a-C) was used in tribo-tests, severe wear of the SS surface occurs, in addition to the tribochemical wear observed for H-DLC, due to the high hardness of the a-C film. PMID- 26844950 TI - Substrate-Controlled, One-Pot Synthesis: Access to Chiral Chroman-2-one and Polycyclic Derivatives. AB - Based on the appropriate choice of electrophiles, one-pot, multicomponent, enantioselective domino reactions have been realized which contain a five-step sequence and provide highly efficient access to potentially bioactive chroman-2 one derivatives as a single diastereoisomer with excellent enantioselectivities and in high yields. This new strategy could significantly improve the previous protocol by directly starting from commercial 2-hydroxybenzaldehydes rather than preformed lactols, which have to be synthesized in several additional steps. PMID- 26844951 TI - Comment on "Metal Semiconductor Field-Effect Transistor with MoS2/Conducting NiOx van der Waals Schottky Interface for Intrinsic High Mobility and Photoswitching Speed". PMID- 26844953 TI - Growth and Structure of the First Layers of Ice on Ru(0001) and Pt(111). AB - Scanning tunneling microscopy was used to probe the structure and growth of the first few layers of water on Ru(0001) and Pt(111) at the molecular level. The surface-bound first layer is composed of a mixture of water molecules forming hexagonal structures, both in registry and out-of-registry with the substrate atoms. The hexagons are connected by pentagonal and heptagonal units. At temperatures below 140 K, this layer structure gives rise to the growth of metastable amorphous structures in the second and higher layers. We found that in the transition from amorphous to crystalline ice the structure of the original bottom layer changes to one in perfect local registry with the hexagonal surfaces of Ru(0001) and Pt(111). We further discovered structural defects in the form of extended one-dimensional lines of five- and eight-membered rings that are domain boundaries and stacking faults in the growing ice layers, which lead to the formation of metastable cubic ice. PMID- 26844954 TI - Low-Resistance 2D/2D Ohmic Contacts: A Universal Approach to High-Performance WSe2, MoS2, and MoSe2 Transistors. AB - We report a new strategy for fabricating 2D/2D low-resistance ohmic contacts for a variety of transition metal dichalcogenides (TMDs) using van der Waals assembly of substitutionally doped TMDs as drain/source contacts and TMDs with no intentional doping as channel materials. We demonstrate that few-layer WSe2 field effect transistors (FETs) with 2D/2D contacts exhibit low contact resistances of ~0.3 kOmega MUm, high on/off ratios up to >10(9), and high drive currents exceeding 320 MUA MUm(-1). These favorable characteristics are combined with a two-terminal field-effect hole mobility MUFE ~ 2 * 10(2) cm(2) V(-1) s(-1) at room temperature, which increases to >2 * 10(3) cm(2) V(-1) s(-1) at cryogenic temperatures. We observe a similar performance also in MoS2 and MoSe2 FETs with 2D/2D drain and source contacts. The 2D/2D low-resistance ohmic contacts presented here represent a new device paradigm that overcomes a significant bottleneck in the performance of TMDs and a wide variety of other 2D materials as the channel materials in postsilicon electronics. PMID- 26844955 TI - Influence of Climate Extremes and Land Use on Fecal Contamination of Shallow Tubewells in Bangladesh. AB - Climate extremes in conjunction with some land use practices are expected to have large impacts on water quality. However, the impacts of land use and climate change on fecal contamination of groundwater has not been well characterized. This work quantifies the influences of extreme weather events and land use practices on Escherichia coli presence and concentration in groundwater from 125 shallow wells, a dominant drinking water resource in rural Bangladesh, monitored over a 17 month period. The results showed that E. coli presence was significantly associated with the number of heavy rain days, developed land and areas with more surface water. These variables also had significant impacts on E. coli concentration, with risk ratios of 1.38 (95% CI = 1.16, 1.65), 1.07 (95% CI: 1.05, 1.09), and 1.02 (95% CI = 1.01, 1.03), respectively. Significant synergistic effects on E. coli presence and concentration were observed when land use and weather variables were combined. The findings suggest that climate extremes and land use practices, particularly urbanization, might promote fecal contamination of shallow well water, thus increasing the risk of diarrheal diseases. PMID- 26844956 TI - Control of Protein Affinity of Bioactive Nanocellulose and Passivation Using Engineered Block and Random Copolymers. AB - We passivated TEMPO-oxidized cellulose nanofibrils (TOCNF) toward human immunoglobulin G (hIgG) by modification with block and random copolymers of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA). The block copolymers reversibly adsorbed on TOCNF and were highly effective in preventing nonspecific interactions with hIgG, especially if short PDMAEMA blocks were used. In such cases, total protein rejection was achieved. This is in contrast to typical blocking agents, which performed poorly. When an anti-human IgG biointerface was installed onto the passivated TOCNF, remarkably high affinity antibody-antigen interactions were observed (0.90 +/- 0.09 mg/m(2)). This is in contrast to the nonpassivated biointerface, which resulted in a significant false response. In addition, regeneration of the biointerface was possible by low pH aqueous wash. Protein A from Staphylococcus aureus was also utilized to successfully increase the sensitivity for human IgG recognition (1.28 +/- 0.11 mg/m(2)). Overall, the developed system based on TOCNF modified with multifunctional polymers can be easily deployed as bioactive material with minimum fouling and excellent selectivity. PMID- 26844957 TI - Thiophene Scaffold as Prospective Central Nervous System Agent: A Review. AB - BACKGROUND: Heterocyclic compounds are extensively dispersed in nature and are vital for life. Various investigational approaches towards Structural Activity Relationship that focus upon the exploration of optimized candidates have become vastly important. METHOD: Literature studies tell that for a series of compounds that are imperative in industrial and medicinal chemistry, thiophene acts as parent. Among various classes of heterocyclic compounds that have potential central nervous system activity, thiophene is the most important one. In the largely escalating chemical world of heterocyclic compounds showing potential pharmacological character, thiophene nucleus has been recognized as the budding entity. RESULT: Seventeen Papers were included in this review article to define the central nervous system potential of thiophene. This review article enlightens the rationalized use and scope of thiophene scaffold as novel central nervous system activity such as anticonvulsant, acetylcholinesterase inhibitor, cyclin dependent kinase 5 (cdk5/p25) inhibitors, CNS depressant, capability to block norepinephrine, serotonin and dopamine reuptake by their respective transporters etc. CONCLUSION: The Finding of this review confirm the importance of thiophene scaffold as potential central nervous system agents. From this outcome, ideas for future molecular modifications leading to the novel derivatives with better constructive pharmacological potential may be derived. PMID- 26844959 TI - Editor Emeritus of The Journal of Neuropsychiatry and Clinical Neurosciences: Stuart C. Yudofsky, M.D. PMID- 26844958 TI - Red blood cell complement receptor one level varies with Knops blood group, alpha(+)thalassaemia and age among Kenyan children. AB - Both the invasion of red blood cells (RBCs) by Plasmodium falciparum parasites and the sequestration of parasite-infected RBCs in the microvasculature are mediated in part by complement receptor one (CR1). RBC surface CR1 level can vary between individuals by more than 20-fold and may be associated with the risk of severe malaria. The factors that influence RBC CR1 level variation are poorly understood, particularly in African populations. We studied 3535 child residents of a malaria-endemic region of coastal Kenya and report, for the first time, that the CR1 Knops blood group alleles Sl2 and McC(b), and homozygous HbSS are positively associated with RBC CR1 level. Sickle cell trait and ABO blood group did not influence RBC CR1 level. We also confirm the previous observation that alpha(+)thalassaemia is associated with reduced RBC CR1 level, possibly due to small RBC volume, and that age-related changes in RBC CR1 expression occur throughout childhood. RBC CR1 level in malaria-endemic African populations is a complex phenotype influenced by multiple factors that should be taken into account in the design and interpretation of future studies on CR1 and malaria susceptibility. PMID- 26844960 TI - Working Memory Models: Insights From Neuroimaging. PMID- 26844961 TI - Depressive Disorder After Pontine Ischemic Stroke: Clinicoradiologic Correlates. PMID- 26844962 TI - Coexistence of Delusional Parasitosis and Complex Visual Hallucinations With Micropsia. PMID- 26844963 TI - Transient Prosopagnosia With Right Temporal Astrocytoma. PMID- 26844964 TI - Corticobasal Syndrome Due to Superficial Siderosis Caused by Thalamic Cavernoma. PMID- 26844965 TI - Influenza-Induced Mania. PMID- 26844966 TI - A Case of Neuropsychiatric Lupus With Severe Malignant Catatonia that Improved With Daily Electroconvulsive Therapy. PMID- 26844967 TI - Acute Mania Induced by Hypothyroidism in a Male Patient After Thyroidectomy. PMID- 26844968 TI - Differential Response to ECT of Psychotic and Affective Symptoms in Huntington's Disease: A Case Report. PMID- 26844969 TI - Probable Ketamine-Induced Hypomanic-Like Episode in a Child With Cerebral Palsy. PMID- 26844970 TI - Through the Eyes of Neglect Patients: A Preliminary Eye-Tracking Study of Unilateral Spatial Neglect. PMID- 26844971 TI - Sympathetic Skin Response in Amyotrophic Lateral Sclerosis. AB - PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive loss of motor neurons, but it is increasingly recognized to be a more disseminated disease. The literature on the involvement of the sympathetic skin response (SSR) in ALS is few. METHODS: We reviewed the literature with specific emphasis on SSR in ALS and investigated SSR in 120 patients with sporadic ALS and in 130 age-matched healthy subjects to determine the effects of SSR in ALS patients. The SSR was conducted in all ALS patients and healthy subjects. RESULTS: We found prolonged mean SSR latency in ALS patients, and the mean SSR amplitude is reduced compared with that of control subjects, especially in their low extremities (P < 0.05). The disease duration seems to have little impact on the SSR latency and amplitude (P > 0.05). Yet, whichever arm or leg involved, the overall difference in lower extremity SSR measurements between the two groups is significant (P < 0.05). And there is no correlation between initial manifestation of autonomic nervous impairment and amplitude and latency of SSR (P > 0.05). CONCLUSIONS: The SSR impairment occurs mainly in lower extremities, which is earlier than clinical manifestation of autonomic nervous impairment in ALS. This may be a subclinical manifestation of ALS. We hypothesize that these results are caused by damage to the unmyelinated postganglionic fibers in ALS patients. PMID- 26844972 TI - Highly Epileptiform Bursts Are Associated With Seizure Recurrence. AB - PURPOSE: Pharmacologic sedation is often used to induce burst suppression in cases of refractory status epilepticus, but there is little evidence to guide the weaning of sedation. Similarly, the morphologic feature of bursts is of unknown clinical relevance. Recently, the standardized American Clinical Neurophysiology Society terminology of critical care EEG introduced the term highly epileptiform bursts (HEBs). Knowing the association of HEBs with seizure may direct the therapy for refractory status epilepticus. METHODS: Consecutive adult patients classified as having burst suppression were identified in our EEG database. Those of an anoxic etiology were excluded. Available EEG records were reviewed, both visually and quantitatively, for the presence of burst suppression. Using the American Clinical Neurophysiology Society terminology, burst suppression was dichotomized into HEBs or nonepileptiform bursts. Periods of transition out of burst suppression were identified, and whether burst suppression was followed by seizure or a continuous slow EEG within 24 hours was determined. RESULTS: Twenty four patients were identified with a burst suppression pattern followed by either seizure or a continuous slow EEG within 24 hours, with some patients having multiple (maximal 5) transitions out of burst suppression, for a total of 33 examples of burst suppression. HEBs were associated with subsequent seizure (P = 0.0001), independent of medication exposure. CONCLUSIONS: Whether or not HEBs are indeed predictive of recurrent seizure or may be used to direct the therapy for status epilepticus, specifically the weaning of anesthetic medications, requires further prospective study in a larger cohort of patients. PMID- 26844973 TI - Rapid discrimination of bacteria using a miniature mass spectrometer. AB - Bacteria colonies were analyzed using paper spray ionization coupled with a portable mass spectrometer. The spectra were averaged and processed using multivariate analysis to discriminate between different species of bacteria based on their unique phospholipid profiles. Full scan mass spectra and product ion MS/MS data were compared to those recorded using a benchtop linear ion trap mass spectrometer. PMID- 26844974 TI - ET-1 Stimulates Superoxide Production by eNOS Following Exposure of Vascular Endothelial Cells to Endotoxin. AB - It has been shown that microcirculation is hypersensitized to endothelin1 (ET-1) following endotoxin (lipopolysaccharide [LPS]) treatment leading to an increased vasopressor response. This may be related in part to decreased activation of endothelial nitric oxide synthase (eNOS) by ET-1. eNOS can also be uncoupled to produce superoxide (O2). This aberrant eNOS activity could further contribute to the hyperconstriction and injury caused by ET-1 following LPS. We therefore tested whether LPS affects ROS production by vascular endothelial cells and whether and how this effect is altered by ET-1. Human umbilical vein endothelial cells (HUVEC) or human microvascular endothelial cells (HMEC) were subjected to a 6-h treatment with LPS (250 ng/mL) or LPS and sepiapterin (100 MUM) followed by a 30-min treatment with 100 MUM L-Iminoethyl Ornithine (L-NIO) an irreversible eNOS inhibitor and 30-min treatment with ET-1 (10 nM). Conversion of [H]L-arginine to [H]L-citrulline was used to measure eNOS activity. Superoxide dismutase (SOD) inhibitable reduction of Cytochrome-C, dihydro carboxy fluorescein (DCF), and Mitosox was used to estimate ROS. LT-SDS PAGE was used to assess the degree of monomerization of the eNOS homodimer. Stimulation of HUVECs with ET-1 significantly increased NO synthesis by 1.4-fold (P < 0.05). ET-1 stimulation of LPS-treated HUVECs failed to increase NO production. Western blot for eNOS protein showed no change in eNOS protein levels. LPS alone resulted in an insignificant increase in ROS production as measured by cytochrome C that was increased 4.6-fold by ET-1 stimulation (P < 0.05). L-NIO significantly decreased ET-1-induced ROS production (P < 0.05). Sepiapterin significantly decreased ROS production in both; unstimulated and ET-1-stimulated LPS-treated groups, but did not restore NO production. DCF experiments confirmed intracellular ROS while Mitosox suggested a non-mitochondrial source. ET-1 treatment following a chronic LPS stress significantly monomerized the eNOS homodimer that was inhibited by sepiapterin loading. The two concomitant phenomena of decreased NO production and increased ROS formation seem to be multifactorial in nature with ROS production dependent upon pterin availability. PMID- 26844976 TI - Protective Effects of Ultramicronized Palmitoylethanolamide (PEA-um) in Myocardial Ischaemia and Reperfusion Injury in VIVO. AB - Myocardial infarction is the leading cause of death, occurs after prolonged ischemia of the coronary arteries. Restore blood flow is the first intervention help against heart attack. However, reperfusion of the arteries leads to ischemia/reperfusion injury (I/R). The fatty acid amide palmitoylethanolamide (PEA) is an endogenous compound widely present in living organisms, with analgesic and anti-inflammatory properties. The present study evaluated the effect of ultramicronized palmitoylethanolamide (PEA-um) treatment on the inflammatory process associated with myocardial I/R. Myocardial ischemia reperfusion injury was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 2 h of reperfusion. PEA-um, was administered (10 mg/kg) 15 min after ischemia and 1 h after reperfusion. In this study, we demonstrated that PEA-um treatment reduces myocardial tissue injury, neutrophil infiltration, adhesion molecules (ICAM-1, P-selectin) expression, proinflammatory cytokines (TNF-alpha, IL-1beta) production, nitrotyrosine and PAR formation, nuclear factor kB expression, and apoptosis (Fas-L, Bcl-2) activation. In addition to study whether the protective effect of PEA-um on myocardial ischemia reperfusion injury is also related to the activation of PPAR-alpha, in a separate set of experiments it has been performed myocardial I/R in PPARalpha mice. Genetic ablation of peroxisome proliferator activated receptor (PPAR)-alpha in PPAR-alphaKO mice exacerbated Myocardial ischemia reperfusion injury when compared with PPAR-alphaWT mice. PEA-um induced cardioprotection in PPAR-alpha wild-type mice, but the same effect cannot be observed in PPAR-alphaKO mice. Our results have clearly shown a modulation of the inflammatory process, associated with myocardial ischemia reperfusion injury, following administration of PEA-um. PMID- 26844977 TI - Effects of Stomach Inflation on Cardiopulmonary Function and Survival During Hemorrhagic Shock: A Randomized, Controlled, Porcine Study. AB - BACKGROUND: Ventilation of an unprotected airway may result in stomach inflation. The purpose of this study was to evaluate the effect of clinically realistic stomach inflation on cardiopulmonary function during hemorrhagic shock in a porcine model. METHODS: Pigs were randomized to a sham control group (n = 9), hemorrhagic shock (35 mL kg over 15 min [n = 9]), and hemorrhagic shock combined with stomach inflation (35 mL kg over 15 min and 5 L stomach inflation [n = 10]). RESULTS: When compared with the control group, hemorrhagic shock (n = 9) increased heart rate (103 +/- 11 vs. 146 +/- 37 beats min; P = 0.002) and lactate (1.4 +/- 0.5 vs. 4.0 +/- 1.9 mmol L; P < 0.001), and decreased mean arterial blood pressure (81.3 +/- 12.8 vs. 35.4 +/- 8.1 mmHg; P < 0.001) and stroke-volume index (38.1 +/- 6.4 vs. 13.6 +/- 4.8 mL min m; P < 0.001). Hemorrhagic shock combined with stomach inflation (n = 10) versus hemorrhagic shock only (n = 9) increased intra-abdominal pressure (27.0 +/- 9.3 vs. 1.1 +/- 1.0 mmHg; P < 0.001), and decreased stroke-volume index (9.9 +/- 6.0 vs. 20.8 +/- 8.5 mL min m; P = 0.007), and dynamic respiratory system compliance (10.8 +/- 4.5 vs. 38.1 +/- 6.1 mL cmH2O; P < 0.001). Before versus after stomach evacuation during hemorrhagic shock, intra-abdominal pressure decreased (27.0 +/- 9.3 vs. 9.8 +/- 5.4 mmHg; P = 0.042). Survival in the sham control and hemorrhagic shock group was 9 of 9, respectively, and 3 of 10 after hemorrhagic shock and stomach inflation (P < 0.001). CONCLUSIONS: During hemorrhagic shock stomach inflation caused an abdominal compartment syndrome and thereby impaired cardiopulmonary function and aerobic metabolism, and increased mortality. Subsequent stomach evacuation partly reversed adverse stomach-inflation triggered effects. PMID- 26844975 TI - Choice of Fluid Therapy in the Initial Management of Sepsis, Severe Sepsis, and Septic Shock. AB - Sepsis results in disruption of the endothelial glycocalyx layer and damage to the microvasculature, resulting in interstitial accumulation of fluid and subsequently edema. Fluid resuscitation is a mainstay in the initial treatment of sepsis, but the choice of fluid is unclear. The ideal resuscitative fluid is one that restores intravascular volume while minimizing edema; unfortunately, edema and edema-related complications are common consequences of current resuscitation strategies. Crystalloids are recommended as first-line therapy, but the type of crystalloid is not specified. There is increasing evidence that normal saline is associated with increased mortality and kidney injury; balanced crystalloids may be a safer alternative. Albumin is similar to crystalloids in terms of outcomes in the septic population but is costlier. Hydroxyethyl starches appear to increase mortality and kidney injury in the critically ill and are no longer indicated in these patients. In the trauma population, the shift to plasma-based resuscitation with decreased use of crystalloid and colloid in the treatment of hemorrhagic shock has led to decreased inflammatory and edema-mediated complications. Studies are needed to determine if these benefits also occur with a similar resuscitation strategy in the setting of sepsis. PMID- 26844978 TI - Disparities in Consistent Retention in HIV Care--11 States and the District of Columbia, 2011-2013. AB - In 2013, 45% of new human immunodeficiency virus (HIV) infection diagnoses occurred in non-Hispanic blacks/African Americans (blacks) (1), who represent 12% of the U.S. POPULATION: * Antiretroviral therapy (ART) improves clinical outcomes and reduces transmission of HIV, which causes acquired immunodeficiency syndrome (AIDS) (2). Racial/ethnic disparities in HIV care limit access to ART, perpetuating disparities in survival and reduced HIV transmission. National HIV Surveillance System (NHSS) data are used to monitor progress toward reaching the National HIV/AIDS Strategy goals to improve care among persons living with HIV and to reduce HIV-related disparities.(?) CDC used NHSS data to describe retention in HIV care over 3 years and describe differences by race/ethnicity. Among persons with HIV infection diagnosed in 2010 who were alive in December 2013, 38% of blacks with HIV infection were consistently retained in care during 2011-2013, compared with 50% of Hispanics/Latinos (Hispanics) and 49% of non Hispanic whites (whites). Differences in consistent retention in care by race/ethnicity persisted when groups were stratified by sex or transmission category. Among blacks, 35% of males were consistently retained in care compared with 44% of females. Differences in HIV care retention by race/ethnicity were established during the first year after diagnosis. Efforts to establish early HIV care among blacks are needed to mitigate racial/ethnic disparities in HIV outcomes over time. PMID- 26844979 TI - Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents. AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric conditions affecting children and adolescents. Amphetamines are among the most commonly prescribed medications to manage ADHD. There are three main classes of amphetamines: dexamphetamine, lisdexamphetamine and mixed amphetamine salts, which can be further broken down into short- and long-acting formulations. A systematic review assessing their efficacy and safety in this population has never been conducted. OBJECTIVES: To assess the efficacy and safety of amphetamines for ADHD in children and adolescents. SEARCH METHODS: In August 2015 we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, ProQuest Dissertation and Theses, and the Networked Digital Library of Theses and Dissertations. We also searched ClinicalTrials.gov, and checked the reference lists of relevant studies and reviews identified by the searches. No language or date restrictions were applied. SELECTION CRITERIA: Parallel-group and cross-over randomized controlled trials (RCTs) comparing amphetamine derivatives against placebo in a pediatric population (< 18 years) with ADHD. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data on participants, settings, interventions, methodology, and outcomes for each included study. For continuous outcomes, we calculated the standardized mean difference (SMD) and for dichotomous outcomes we calculated the risk ratio (RR). Where possible, we conducted meta-analyses using a random-effects model. We also performed a meta analysis of the most commonly reported adverse events in the primary studies. MAIN RESULTS: We included 23 trials (8 parallel-group and 15 cross-over trials), with 2675 children aged three years to 17 years. All studies compared amphetamines to placebo. Study durations ranged from 14 days to 365 days, with the majority lasting less than six months. Most studies were conducted in the United States; three studies were conducted across Europe. We judged 11 included studies to be at a high risk of bias due to insufficient blinding methods, failing to account for dropouts and exclusions from the analysis, and failing to report on all outcomes defined a priori. We judged the remaining 12 studies to be at unclear risk of bias due to inadequate reporting.Amphetamines improved total ADHD core symptom severity according to parent ratings (SMD -0.57; 95% confidence interval (CI) -0.86 to -0.27; 7 studies; 1247 children/adolescents; very low quality evidence), teacher ratings (SMD -0.55; 95% CI -0.83 to -0.27; 5 studies; 745 children/adolescents; low quality evidence), and clinician ratings (SMD 0.84; 95% CI -1.32 to -0.36; 3 studies; 813 children/adolescents; very low quality evidence). In addition, the proportion of responders as rated by the Clinical Global Impression - Improvement (CGI-I) scale was higher when children were taking amphetamines (RR 3.36; 95% CI 2.48 to 4.55; 9 studies; 2207 children/adolescents; very low quality evidence).The most commonly reported adverse events included decreased appetite, insomnia/trouble sleeping, abdominal pain, nausea/vomiting, headaches, and anxiety. Amphetamines were associated with a higher proportion of participants experiencing decreased appetite (RR 6.31; 95% CI 2.58 to 15.46; 11 studies; 2467 children/adolescents), insomnia (RR 3.80; 95% CI 2.12 to 6.83; 10 studies; 2429 children/adolescents), and abdominal pain (RR 1.44; 95% CI 1.03 to 2.00; 10 studies; 2155 children/adolescents). In addition, the proportion of children who experienced at least one adverse event was higher in the amphetamine group (RR 1.30; 95% CI 1.18 to 1.44; 6 studies; 1742 children/adolescents; low quality evidence).We performed subgroup analyses for amphetamine preparation (dexamphetamine, lisdexamphetamine, mixed amphetamine salts), amphetamine release formulation (long acting versus short acting), and funding source (industry versus non industry). Between-group differences were observed for proportion of participants experiencing decreased appetite in both the amphetamine preparation (P < 0.00001) and amphetamine release formulation (P value = 0.008) subgroups, as well as for retention in the amphetamine release formulation subgroup (P value = 0.03). AUTHORS' CONCLUSIONS: Most of the included studies were at high risk of bias and the overall quality of the evidence ranged from low to very low on most outcomes. Although amphetamines seem efficacious at reducing the core symptoms of ADHD in the short term, they were associated with a number of adverse events. This review found no evidence that supports any one amphetamine derivative over another, and does not reveal any differences between long-acting and short-acting amphetamine preparations. Future trials should be longer in duration (i.e. more than 12 months), include more psychosocial outcomes (e.g. quality of life and parent stress), and be transparently reported. PMID- 26844980 TI - Recent advances in superhydrophobic surfaces and their relevance to biology and medicine. AB - By mimicking naturally occurring superhydrophobic surfaces, scientists can now realize artificial surfaces on which droplets of a few microliters of water are forced to assume an almost spherical shape and an extremely high contact angle. In recent decades, these surfaces have attracted much attention due to their technological applications for anti-wetting and self-cleaning materials. Very recently, researchers have shifted their interest to investigate whether superhydrophobic surfaces can be exploited to study biological systems. This research effort has stimulated the design and realization of new devices that allow us to actively organize, visualize and manipulate matter at both the microscale and nanoscale levels. Such precise control opens up wide applications in biomedicine, as it allows us to directly manipulate objects at the typical length scale of cells and macromolecules. This progress report focuses on recent biological and medical applications of superhydrophobicity. Particular regard is paid to those applications that involve the detection, manipulation and study of extremely small quantities of molecules, and to those that allow high throughput cell and biomaterial screening. PMID- 26844981 TI - Continuing Education- "The Action Level"(r). AB - Access "The Action Level,"(r) Questions online at: http://www.acgih.org/products/joeh/alquestions.htm Access "The Action Level,"(r) Answers online at: http://www.acgih.org/products/joeh/alanswers.htm Access "The Action Level,"(r) Registration Form online at: http://www.acgih.org/products/joeh/alregfrm.htm "The Action Level,"(r) a self study, continuing education program, provides a convenient and interesting opportunity for individuals to expand their knowledge in relevant areas of industrial hygiene, as well as occupational and environmental safety and health. The program is approved by both the American Board of Industrial Hygiene, and the Board of Certified Safety Professionals, which award Certification Maintenance (CM) points and Continuance of Certification (COC) points, respectively, for successful participation. Participants must read each issue of the Journal, answer "The Action Level"(r) questions, and return the completed answer sheet at the end of that issue's "The Action Level"(r) column. To earn the designated CM or COC credit, a score of 70 percent or better is required within a 12-month period. Certified Industrial Hygienists and Certified Associate Industrial Hygienists may earn 2 points per year. Certified Safety Professionals may earn 1.2 points per year. Enrollment is possible each month, but points are awarded only four times each year-in March, June, September, and December-to participants who score an average of 70 percent or better within each three-month period. If you register in March 2010, you will not receive CM points and/or COC points until the following quarter. In the next quarter, you'll receive 0.5 CM points and/or 0.3 COC points after satisfactorily completing answer sheets for the April, May, and June 2010 issues, and so on. To enroll, complete the registration form and the answer sheet at the end of this "The Action Level"(r) column. The cost is $199 (ACGIH(r)/AIHA members)/$219 (nonmembers) for one year. Nonmembers are encouraged to become members to take advantage of the member discount. For more information regarding ACGIH(r) membership, call 513-742-2020, or apply on line at http://www.acgih.org/members/memberform.htm . Checks must be in U.S. currency, drawn on a U.S. bank, and payable to ACGIH(r). We also accept AmEx, MasterCard, Discover, and VISA. This continuing education program fee is separate from the Journal subscription cost. The fee covers administration costs and is nonrefundable. Submissions must be received by the date listed on each answer sheet. PMID- 26844982 TI - Comparative effectiveness research in the U.S.A.: when will there be an impact on healthcare decision-making? AB - Five annual surveys of healthcare decision-makers potentially affected by comparative effectiveness research (CER) indicate sustained recognition of its importance and potential impact. Initial expectations of immediate CER impact have over time turned to stakeholder assessments of little short-term impact. In successive surveys, they project a continuous horizon of 3-5 years for CER to have a moderate or substantial improvement in decision making. The prominence of Patient-Centered Outcomes Research Institute in CER is highlighted by stakeholders, but greater emphasis on translating and disseminating research findings is needed, a role in which Agency for Healthcare Research and Quality is expected to contribute. Stakeholders, including patients, must be engaged throughout to ensure that findings provide the flexibility for decision makers to apply them to their patient populations. PMID- 26844983 TI - Active performance of tetrahedral groups to SHG response: theoretical interpretations of Ge/Si-containing borate crystals. AB - As potential candidates for deep-UV nonlinear optical (NLO) crystals, borosilicates and borogermanates, which contain NLO-active groups such as B-O, Si O and Ge-O, have fascinated many scientists. The crystal structures, electronic structures and optical properties of seven borates in different B/R (R = Si, Ge) ratios have been studied using DFT methods. Through the SHG-density, we find that besides the recognized contribution of the pi-conjugation configuration of BO3 to second harmonic generation (SHG), the tetrahedra have a non-negligible influence. This is because the non-bonding p orbitals of the bridging oxygen in the tetrahedra are observably closer to the Fermi level than those in BO3, which is observed in the PDOS of Rb4Ge3B6O17 and RbGeB3O7. This conclusion would be very meaningful in the understanding of the relationship between the crystal structure and nonlinear optical properties. PMID- 26844984 TI - New and emerging developments in extensive-stage small cell lung cancer therapeutics. AB - PURPOSE OF REVIEW: Extensive-stage small cell lung cancer (ES-SCLC) remains a disease with a dismal prognosis, with median survival of approximately 8-10 months. Despite many attempts to develop effective systemic therapies, very little progress has been made in the last several decades. Platinum-based combination chemotherapy remains the standard of care in the first-line setting and is associated with high response rates albeit short-lived. However, there have been recent advances in the use of radiation therapy, as well as new insights into the biology of SCLC. RECENT FINDINGS: Some of the most appreciable advances in the last decade have involved the use of local radiation therapy. With the use of new laboratory techniques such as genomic sequencing, there remains promise of rationally targeted drug development. Circulating tumor cell research may also provide insights to SCLC biology and further refine treatment. SUMMARY: Systemic therapy for SCLC has changed little over the past 30 years with the most significant advances in ES-SCLC relating to radiotherapy rather than systemic therapy. The effectiveness of prophylactic cranial irradiation and thoracic radiotherapy has renewed interest in therapeutics focused on the modulation of DNA damage or repair. Recent developments in genomic sequencing and immunotherapy may translate to new treatment paradigms for SCLC. PMID- 26844985 TI - Experimental treatment strategies in primary cutaneous T-cell lymphomas. AB - PURPOSE OF REVIEW: Cutaneous T-cell lymphoma (CTCL) comprises a heterogeneous group of malignancies derived from skin-homing or resident T cells. Effective treatments are limited, thus new therapies are in development to address the unmet medical need. RECENT FINDINGS: Recent studies uncovering the genetic alteration in cutaneous T-cell lymphoma have enhanced our understanding of the importance of the T-cell activation/survival pathways, dysregulated immune system, and the relevance of chromatin modification in the pathogenesis of CTCL. New advances in cancer immunomodulation such as with PD1/PD-L1 inhibitors and novel targeted antitumor therapies such as brentuximab vedotin and mogamulizumab as well as potential combination strategies are promising for improving clinical efficacy with manageable toxicity profile. SUMMARY: All these new therapeutic approaches have resulted in broadening the treatment landscape and a potential paradigm shift in the management of CTCL. PMID- 26844986 TI - The role of mitogen-activated protein targeting in melanoma beyond BRAFV600. AB - PURPOSE OF REVIEW: Targeted therapy in melanoma is well established for patients with tumors harboring BRAF mutations, but less so for other molecularly defined subsets. In this review, emerging preclinical, genomic, and early clinical data are discussed regarding the use of mitogen-activated protein (MAPK) pathway inhibitors in other molecular subsets of melanoma. RECENT FINDINGS: There are now four well defined subsets of melanoma based on The Cancer Genome Atlas: BRAF driven, NRAS driven, NF1 mutant, and 'triple wild type'. The former three subtypes predict signaling through the MAPK pathway and sensitivity to inhibitors of this pathway's mediators. With ongoing translation of preclinical findings into clinical trials, there is great hope that these strategies will improve the care of patients who fall into these other molecular subsets. SUMMARY: A more comprehensive understanding of genetically defined subtypes of melanoma is emerging. Efforts in the clinic are already underway, but additional, well designed trials of MAPK-targeted therapy planned and needed. PMID- 26844988 TI - Informatics in neurocritical care: new ideas for Big Data. AB - PURPOSE OF REVIEW: Big data is the new hype in business and healthcare. Data storage and processing has become cheap, fast, and easy. Business analysts and scientists are trying to design methods to mine these data for hidden knowledge. Neurocritical care is a field that typically produces large amounts of patient related data, and these data are increasingly being digitized and stored. This review will try to look beyond the hype, and focus on possible applications in neurointensive care amenable to Big Data research that can potentially improve patient care. RECENT FINDINGS: The first challenge in Big Data research will be the development of large, multicenter, and high-quality databases. These databases could be used to further investigate recent findings from mathematical models, developed in smaller datasets. Randomized clinical trials and Big Data research are complementary. Big Data research might be used to identify subgroups of patients that could benefit most from a certain intervention, or can be an alternative in areas where randomized clinical trials are not possible. SUMMARY: The processing and the analysis of the large amount of patient-related information stored in clinical databases is beyond normal human cognitive ability. Big Data research applications have the potential to discover new medical knowledge, and improve care in the neurointensive care unit. PMID- 26844989 TI - Increased pressure within the abdominal compartment: intra-abdominal hypertension and the abdominal compartment syndrome. AB - PURPOSE OF REVIEW: This article reviews recent developments related to intra abdominal hypertension (IAH)/abdominal compartment syndrome (ACS) and clinical practice guidelines published in 2013. RECENT FINDINGS: IAH/ACS often develops because of the acute intestinal distress syndrome. Although the incidence of postinjury ACS is decreasing, IAH remains common and associated with significant morbidity and mortality among critically ill/injured patients. Many risk factors for IAH include those findings suggested to be indications for use of damage control surgery in trauma patients. Medical management strategies for IAH/ACS include sedation/analgesia, neuromuscular blocking and prokinetic agents, enteral decompression tubes, interventions that decrease fluid balance, and percutaneous catheter drainage. IAH/ACS may be prevented in patients undergoing laparotomy by leaving the abdomen open where appropriate. If ACS cannot be prevented with medical or surgical management strategies or treated with percutaneous catheter drainage, guidelines recommend urgent decompressive laparotomy. Use of negative pressure peritoneal therapy for temporary closure of the open abdomen may improve the systemic inflammatory response and patient-important outcomes. SUMMARY: In the last 15 years, investigators have better clarified the pathogenesis, epidemiology, diagnosis, and appropriate prevention of IAH/ACS. Subsequent study should be aimed at understanding which treatments effectively lower intra abdominal pressure and whether these treatments ultimately affect patient important outcomes. PMID- 26844990 TI - Light sheet fluorescence microscopy for in situ cell interaction analysis in mouse lymph nodes. AB - Reactive lymph nodes (LNs) are sites where pMHC-loaded dendritic cells (DCs) interact with rare cognate T cells, leading to their clonal expansion. While DC interactions with T cell subsets critically shape the ensuing immune response, surprisingly little is known on their spatial orchestration at physiologically T cell low precursor frequencies. Light sheet fluorescence microscopy and one of its implementations, selective plane illumination microscopy (SPIM), is a powerful method to obtain precise spatial information of entire organs of 0.5 10mm diameter, the size range of murine LNs. Yet, its usefulness for immunological research has thus far not been comprehensively explored. Here, we have tested and defined protocols that preserve fluorescent protein function during lymphoid tissue clearing required for SPIM. Reconstructions of SPIM generated 3D data sets revealed that calibrated numbers of adoptively transferred T cells and DCs are successfully detected at a single cell level within optically cleared murine LNs. Finally, we define parameters to quantify specific interactions between antigen-specific T cells and pMHC-bearing DCs in murine LNs. In sum, our studies describe the successful application of light sheet fluorescence microscopy to immunologically relevant tissues. PMID- 26844992 TI - Masters of complexity. PMID- 26844991 TI - Science Educational Outreach Programs That Benefit Students and Scientists. AB - Both scientists and the public would benefit from improved communication of basic scientific research and from integrating scientists into education outreach, but opportunities to support these efforts are limited. We have developed two low cost programs--"Present Your PhD Thesis to a 12-Year-Old" and "Shadow a Scientist"--that combine training in science communication with outreach to area middle schools. We assessed the outcomes of these programs and found a 2-fold benefit: scientists improve their communication skills by explaining basic science research to a general audience, and students' enthusiasm for science and their scientific knowledge are increased. Here we present details about both programs, along with our assessment of them, and discuss the feasibility of exporting these programs to other universities. PMID- 26844993 TI - I will click those boxes, but first, I will care for my patient. PMID- 26844994 TI - Prolotherapy: Can it help your patient? PMID- 26844995 TI - Home apnea monitors--when to discontinue use. PMID- 26844996 TI - Weight loss . fatigue . joint pain . Dx? PMID- 26844997 TI - ACIP weighs in on meningococcal B vaccines. PMID- 26844998 TI - Young man with unexplained hair loss. PMID- 26844999 TI - Help Desk Answers: Is prazosin effective for PTSD-associated nightmares? PMID- 26845000 TI - Erratum. PMID- 26845001 TI - Causes of peripheral neuropathy: Diabetes and beyond. PMID- 26845002 TI - PURLs: Should you bypass anticoagulant "bridging" before and after surgery? PMID- 26845003 TI - Help Desk Answers: What is the optimal duration of PPI therapy for healing an ulcer? PMID- 26845004 TI - When it's beneficial to defer dialysis. PMID- 26845005 TI - Clinical Inquiry: What's the best way to predict the success of a trial of labor after a previous C-section? AB - Seven validated prospective scoring systems, and one unvalidated system, predict a successful TOLAC based on a variety of clinical factors. The systems use different outcome statistics, so their predictive accuracy can't be directly compared. PMID- 26845006 TI - The use of dual antiplatelet therapy in high-risk patients with acute coronary syndromes. PMID- 26845007 TI - Hot Topics in Primary Care: Colorectal Cancer Screening. AB - Colorectal cancer is a generally slow-growing cancer that is highly curable when detected at an early, localized stage. Dueto the lack of symptoms, even with advanced disease, screening is required to ensure cancers are detected early. Currently,however, only 3 in 5 people eligible for CRC screening undergo screening. Barriers vary somewhat by screening test and may differ in individual patients. Screening tests are generally more affordable due to recent changes in Medicare and private insurance coverage. Discussion with patients to identify barriers to screening makes it possible to select among the currently available invasive and noninvasive screening tests to determine the test that best meets the patient's health needs with the overall goal of increasing screening for a preventable disease. PMID- 26845008 TI - Hot Topics in Primary Care: Individualizing Pharmacologic Management of Irritable Bowel Syndrome. AB - Irritable bowel syndrome is a common gastrointestinal disorder with constipation, diarrhea, and mixed subtypes. The diagnosis is generally based on a detailed history utilizing the Rome III criteria. Alarm signals necessitate more extensive diagnostic evaluation. Nonpharmacologic options and over-the-counter remedies (e.g., loperamide) might not be supported by strong evidence, but are often chosen as initial treatment for their safety and tolerability. Psychological interventions may be beneficial. Newer pharmacologic agents such as alosetron, eluxadoline, linaclotide, lubiprostone, and rifaximin are supported by higher quality evidence than older agents such as antispasmodics and laxatives. Patients with IBS commonly report that clinicians offer insufficient empathy and validation of their symptoms. Physicians therefore should strive to improve communication methods that specifically provide such reassurance. Individualizing treatment based on patient values and preferences is essential. PMID- 26845009 TI - Hot Topics in Primary Care: Familial Hypercholesterolemia in Youth. AB - Worldwide, guidelines support early identification, aggressive lifestyle management, and pharmacologic lipid lowering therapies when appropriate in youth with FH. These guidelines are aimed at improving the unending cycle of premature CHD in families despite the vast body of knowledge regarding the natural history of undiagnosed and untreated FH. Although valid concerns have been raised about treating youth other than those with FH with lipid-lowering pharmaceuticals, we believe the preponderance of the evidence laid forth by multiple professional societies from the United States and abroad is clearly weighted in favor of early diagnosis and treatment with lifestyle modification, to prevent the acquisition of other risk factors, and habituation to lifelong low-fat diet and adequate physical activity. We can think of no other instance where providers in the field of family medicine could have such a profound impact on the current and future health of child and parent and even future generations. PMID- 26845010 TI - Hot Topics in Primary Care: Update on the Recognition and Management of Gout: More Than the Great Toe. AB - Gout is a chronic inflammatory condition that is increasing in prevalence and commonly associated with other chronic diseases such as obesity, diabetes mellitus, hypertension, hypercholesterolemia, chronic kidney disease, cardiovascular disease, and thromboembolic disorders. These associations make the management of patients with gout more complex. Although identification of MSU crystals in synovial fluid is diagnostic, a presumptive diagnosis of gout can be made clinically based on the presence of hyperuricemia, rapid development of pain, tenderness, and swelling in a single toe (male) or elbow or finger joint (female), and family history. Gout is increasingly recognized as a heterogeneous disease requiring individualized treatment. A healthy lifestyle is always recommended and patient education is critical to support self-management and long term adherence. Antiinflammatory therapy, typically colchicine or an NSAID, is recommended for management of an acute gout flare, while ULT may be used in patients with frequent or severe acute gout, tophi, urolithiasis, renal function impairment, or other complications of gout. Allopurinol is first-line ULT for most patients, although febuxostat and probenecid are effective options and pegloticase is useful in selected patients. New medications, such as lesinurad, are on the horizon. PMID- 26845011 TI - Hot Topics in Primary Care: Pharmacologic Approach to Obesity. PMID- 26845012 TI - Hot Topics in Primary Care: Management of Opioid-induced Constipation. AB - Constipation is a common complication of opioid therapy that contributes to substantial patient morbidity, decreased productivity, and opioid nonadherence. Other causes of constipation may occur concomitantly and should be investigated. Although evidence supporting their use is limited, the use of fiber, water, laxatives, and/or exercise is recommended in current guidelines as initial management. Peripherally acting MU-opioid receptor antagonists are important treatment options, are well-tolerated, and improve many signs and symptoms of OIC in patients taking an opioid for chronic noncancer pain. PMID- 26845013 TI - Hot Topics in Primary Care: Ambulatory Glucose Profiling. PMID- 26845014 TI - Hot Topics in Primary Care: Innovations in Insulin for Type 2 Diabetes Mellitus. AB - Insulin formulations have undergone significant improvements in recent decades. While insulin is a recommended treatment option across the spectrum of treatment for patients with T2DM, unmet clinical needs remain. Three insulin formulations were recently approved in the United States and others are in late-stage development with features that address one or more of these unmet clinical needs. PMID- 26845015 TI - Hot Topics in Primary Care: Role of the Kidney and SGLT-2 Inhibition in Type 2 Diabetes Mellitus. AB - SGLT-2 inhibitors provide a complementary mechanism of glucose lowering and can be used as monotherapy or in combination with other medications, including insulin. In addition to improved glycemic control, which generally is maintained over 2 years, SGLT-2 inhibitors provide reductions in body weight and systolic blood pressure. Increases in LDL-C and HDL-C also have been observed. A requirement for adequate renal function is a limitation in patients with CKD. A low incidence of hypoglycemia, ability to promote weight loss, and availability as an oral formulation diminish common barriers to glucose-lowering therapy. PMID- 26845016 TI - Hot Topics in Primary Care: Considerations in the Selection of Antihyperglycemic Therapy for Older Patients With Type 2 Diabetes Mellitus: A Focus on Newer Therapies. AB - Treatment of type 2 diabetes mellitus (T2DM) in older patients is complicated by a variety of factors and requires an individualized approach. Benefits of intensive glycemic control must be weighed against associated risks. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, and sodium glucose cotransporter-2 inhibitors are newer antihyperglycemic agents that effectively lower glycated hemoglobin levels, with a low risk of hypoglycemia, and have a neutral or beneficial effect on weight. The purpose of this review is to discuss challenges in treating older patients with T2DM, and the efficacy and safety of these newer classes based on clinical trials in older populations. PMID- 26845017 TI - Hot Topics in Primary Care: Nonsteroidal Anti- inflammatory Drugs and Cardiovascular Risk: Where Are We Today? PMID- 26845018 TI - Hot Topics in Primary Care: Individualizing Inhaled Medications for Asthma and Allergic Rhinitis. AB - Inhaled medications are important treatment options for asthma and allergic rhinitis. Selecting among the different formulations and delivery devices is important as it impacts adherence and proper use, both of which affect health related outcomes. The wide variety of inhalers now available allows individualizing inhaler selection. PMID- 26845019 TI - Soluble tumor necrosis factor receptors as predictors of 1-year mortality and renal dysfunction after liver transplantation. AB - BACKGROUND: Several risk factors influence survival after liver transplantation (LT). Some research has demonstrated a relationship between soluble tumor necrosis factor receptors (sTNFRs) and worse clinical liver disease outcomes, but there are no data showing an association between sTNFRs and outcomes after LT. The primary aim of this study was to determine whether an association exists between perioperative sTNFRs and renal dysfunction or mortality after LT. METHODS: Data were collected prospectively from 122 patients submitted to deceased-donor orthotopic LT. Blood samples were collected at seven different perioperative times and analyzed by ELISA. The statistical analysis included univariate analysis followed by logistic regression. The predictive value of significant variables was assessed using ROC curves. RESULTS: One-month and 1 year LT survivals were 91% and 81%, respectively. Increased levels of soluble tumor necrosis factor receptor 1 (sTNF-R1) after 24h of graft perfusion were associated with postoperative Renal Replacement Therapy (RRT) (OR 1.25) and 1 year mortality (OR 1.1). RRT was associated with 30-day and 1-year LT mortality, with OR 19.78 and 45.45, respectively. CONCLUSION: A higher sTNF-R1 level measured 24h after graft perfusion is an independent predictor of RRT and 1-year mortality after LT. PMID- 26845020 TI - Monitoring efficiency of humoral rejection episode therapy in liver transplantation: any role for complement binding Luminex Single Antigen assays? AB - Humoral rejection and its relationship with anti HLA antibodies have been extensively studied in organ transplantation with the exception of liver transplantation (LT). Recently, association between donor specific anti HLA antibodies (DSA) and increased risk of rejection and graft loss has been suggested in LT. When such antibodies appear, adequate treatment and monitoring are needed to avoid or delay allograft loss. We report here three cases of probable antibody-mediated rejection developed after pregnancy in liver transplanted women. Sera at the time of rejection and during follow-up have been retrospectively tested for the ability of DSA to bind complement components. These cases display different outcomes depending on the complement binding DSA capacity and titers after treatment of the rejection episodes. Thus, they highlight the potential interest of complement binding Luminex Single Antigen assays to monitor the efficiency of anti-rejection therapy. PMID- 26845021 TI - Expression of surface-associated 82kDa-proMMP-9 in primary acute leukemia blast cells inversely correlates with patients' risk. AB - With its ability to degrade extracellular matrix proteins and activate growth factors and cytokines, matrix metalloproteinase (MMP)-9 is an important regulator of cell function. Previously, we reported that myeloid leukemic cells express a unique 82kDa-proMMP-9 variant on their cell surface that is not affected by its natural inhibitor. In this study, we generated monoclonal antibodies that specifically recognize 82kDa-proMMP-9. Flow cytometry analysis using these antibodies revealed significant surface expression of 82kDa-proMMP-9 in monocytes, but minimal amounts in T and B cells isolated from peripheral blood of nine healthy donors and 22 patients with acute myeloid leukemia (AML). In all AML patients, blasts expressed 82kDa-proMMP-9 at levels of 4%-46%, with significantly higher levels in patients with a better risk defined according to National Comprehensive Cancer Network (NCCN) guidelines (rho = -0.748, p < 0.001) and favorable phenotype according to the French-American-British classification (p = 0.02) compared with patients with adverse prognoses. Receiver operating characteristic curve analysis confirmed the diagnostic accuracy of 82kDa-proMMP-9 measurement in AML blasts (area under the curve: 0.893 [0.739-1.000], p = 0.019). It led us to define a cutoff value of 11.5% for identifying patients with lower NCCN risk (p = 0.005) and with a tendency toward a higher probability of response to anthracycline-based therapy (p = 0.109) and increased event-free survival (p = 0.24). Thus, 82kDa-proMMP-9 expression on blasts may represent a novel independent marker of prognosis in patients with AML. PMID- 26845022 TI - Glutamate cysteine ligase and the age-related decline in cellular glutathione: The therapeutic potential of gamma-glutamylcysteine. AB - A consistent underlying index of aging is a decline in the cellular levels of the tripeptide glutathione (GSH). GSH is an essential thiol antioxidant produced in the cytosol of all cells and plays a key role in protecting against oxidative stress by neutralising free radicals and reactive oxygen species (ROS). The decline in GSH has been associated with changes in the expression and activity of the rate-limiting enzyme glutamate cysteine ligase (GCL), which produces the intermediate dipeptide gamma-glutamylcysteine (gamma-GC). The molecular mechanisms that affect these age-related changes remain unclear due to the complexity of GCL regulation. Impairment of the transcriptional activity of Nrf2 has been demonstrated to contribute to GCL dysregulation in aged rats. However, considering the complex nature of GCL regulation, relatively little research has been conducted to investigate the age-associated post-transcriptional controls of the enzyme. Defining these unknown mechanisms may inform our understanding of the aetiology of many age-related diseases and assist in formulating appropriate therapeutic strategies. This review focuses on the suitability of treatment with exogenous gamma-GC to raise GSH levels by circumventing the age-related dysregulation of the rate-limiting step of GSH, providing promise for future research for the treatment of chronic oxidative stress-related diseases. PMID- 26845023 TI - Properties and catalytic activities of MICAL1, the flavoenzyme involved in cytoskeleton dynamics, and modulation by its CH, LIM and C-terminal domains. AB - MICAL1 is a cytoplasmic 119 kDa protein participating in cytoskeleton dynamics through the NADPH-dependent oxidase and F-actin depolymerizing activities of its N-terminal flavoprotein domain, which is followed by calponin homology (CH), LIM domains and a C-terminal region with Pro-, Glu-rich and coiled-coil motifs. MICAL1 and truncated forms lacking the C-terminal, LIM and/or CH regions have been produced and characterized. The CH, LIM and C-terminal regions cause an increase of Km,NADPH exhibited by the NADPH oxidase activity of the flavoprotein domain, paralleling changes in the overall protein charge. The C-terminus also determines a ~ 10-fold decrease of kcat, revealing its role in establishing an inactive/active conformational equilibrium, which is at the heart of the regulation of MICAL1 in cells. F-actin lowers Km,NADPH (10-50 MUM) and increases kcat (10-25 s(-1)) to similar values for all MICAL forms. The apparent Km,actin of MICAL1 is ~ 10-fold higher than that of the other forms (3-5 MUM), reflecting the fact that F-actin binds to the flavoprotein domain in the MICAL's active conformation and stabilizes it. Analyses of the reaction in the presence of F actin indicate that actin depolymerization is mediated by H2O2 produced by the NADPH oxidase reaction, rather than due to direct hydroxylation of actin methionine residues. PMID- 26845024 TI - Microtubules Inhibit E-Cadherin Adhesive Activity by Maintaining Phosphorylated p120-Catenin in a Colon Carcinoma Cell Model. AB - Tight regulation of cadherin-mediated intercellular adhesions is critical to both tissue morphogenesis during development and tissue homeostasis in adults. Cell surface expression of the cadherin-catenin complex is often directly correlated with the level of adhesion, however, examples exist where cadherin appears to be inactive and cells are completely non-adhesive. The state of p120-catenin phosphorylation has been implicated in regulating the adhesive activity of E cadherin but the mechanism is currently unclear. We have found that destabilization of the microtubule cytoskeleton, independent of microtubule plus end dynamics, dephosphorylates p120-catenin and activates E-cadherin adhesion in Colo 205 cells. Through chemical screening, we have also identified several kinases as potential regulators of E-cadherin adhesive activity. Analysis of several p120-catenin phosphomutants suggests that gross dephosphorylation of p120 catenin rather than that of specific amino acids may trigger E-cadherin adhesion. Uncoupling p120-catenin binding to E-cadherin at the membrane causes constitutive adhesion in Colo 205 cells, further supporting an inhibitory role of phosphorylated p120-catenin on E-cadherin activity. PMID- 26845026 TI - Correction: Structural Changes and Lack of HCN1 Channels in the Binaural Auditory Brainstem of the Naked Mole-Rat (Heterocephalus glaber). PMID- 26845025 TI - Evidence of Alternative Cystatin C Signal Sequence Cleavage Which Is Influenced by the A25T Polymorphism. AB - Cystatin C (Cys C) is a small, potent, cysteine protease inhibitor. An Ala25Thr (A25T) polymorphism in Cys C has been associated with both macular degeneration and late-onset Alzheimer's disease. Previously, studies have suggested that this polymorphism may compromise the secretion of Cys C. Interestingly, we found that untagged A25T, A25T tagged C-terminally with FLAG, or A25T FLAG followed by green fluorescent protein (GFP), were all secreted as efficiently from immortalized human cells as their wild-type (WT) counterparts (e.g., 112%, 100%, and 88% of WT levels from HEK-293T cells, respectively). Supporting these observations, WT and A25T Cys C variants also showed similar intracellular steady state levels. Furthermore, A25T Cys C did not activate the unfolded protein response and followed the same canonical endoplasmic reticulum (ER)-Golgi trafficking pathway as WT Cys C. WT Cys C has been shown to undergo signal sequence cleavage between residues Gly26 and Ser27. While the A25T polymorphism did not affect Cys C secretion, we hypothesized that it may alter where the Cys C signal sequence is preferentially cleaved. Under normal conditions, WT and A25T Cys C have the same signal sequence cleavage site after Gly26 (referred to as 'site 2' cleavage). However, in particular circumstances when the residues around site 2 are modified (such as by the presence of an N-terminal FLAG tag immediately after Gly26, or by a Gly26Lys (G26K) mutation), A25T has a significantly higher likelihood than WT Cys C of alternative signal sequence cleavage after Ala20 ('site 1') or even earlier in the Cys C sequence. Overall, our results indicate that the A25T polymorphism does not cause a significant reduction in Cys C secretion, but instead predisposes the protein to be cleaved at an alternative signal sequence cleavage site if site 2 is hindered. Additional N-terminal amino acids resulting from alternative signal sequence cleavage may, in turn, affect the protease inhibition function of Cys C. PMID- 26845027 TI - Tankyrases Promote Homologous Recombination and Check Point Activation in Response to DSBs. AB - DNA lesions are sensed by a network of proteins that trigger the DNA damage response (DDR), a signaling cascade that acts to delay cell cycle progression and initiate DNA repair. The Mediator of DNA damage Checkpoint protein 1 (MDC1) is essential for spreading of the DDR signaling on chromatin surrounding Double Strand Breaks (DSBs) by acting as a scaffold for PI3K kinases and for ubiquitin ligases. MDC1 also plays a role both in Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR) repair pathways. Here we identify two novel binding partners of MDC1, the poly (ADP-ribose) Polymerases (PARPs) TNKS1 and 2. We find that TNKSs are recruited to DNA lesions by MDC1 and regulate DNA end resection and BRCA1A complex stabilization at lesions leading to efficient DSB repair by HR and proper checkpoint activation. PMID- 26845028 TI - Exploring the Ecological Validity of Thinking on Demand: Neural Correlates of Elicited vs. Spontaneously Occurring Inner Speech. AB - Psychology and cognitive neuroscience often use standardized tasks to elicit particular experiences. We explore whether elicited experiences are similar to spontaneous experiences. In an MRI scanner, five participants performed tasks designed to elicit inner speech (covertly repeating experimenter-supplied words), inner seeing, inner hearing, feeling, and sensing. Then, in their natural environments, participants were trained in four days of random-beep-triggered Descriptive Experience Sampling (DES). They subsequently returned to the scanner for nine 25-min resting-state sessions; during each they received four DES beeps and described those moments (9 * 4 = 36 moments per participant) of spontaneously occurring experience. Enough of those moments included spontaneous inner speech to allow us to compare brain activation during spontaneous inner speech with what we had found in task-elicited inner speech. ROI analysis was used to compare activation in two relevant areas (Heschl's gyrus and left inferior frontal gyrus). Task-elicited inner speech was associated with decreased activation in Heschl's gyrus and increased activation in left inferior frontal gyrus. However, spontaneous inner speech had the opposite effect in Heschl's gyrus and no significant effect in left inferior frontal gyrus. This study demonstrates how spontaneous phenomena can be investigated in MRI and calls into question the assumption that task-created phenomena are often neurophysiologically and psychologically similar to spontaneously occurring phenomena. PMID- 26845029 TI - Oxygen functional groups in graphitic carbon nitride for enhanced photocatalysis. AB - Metal-free semiconductors offer a new opportunity for environmental photocatalysis toward a potential breakthrough in high photo efficiency with complete prevention of metal leaching. In this study, graphitic carbon nitride (GCN) modified by oxygen functional groups was synthesized by a hydrothermal treatment of pristine GCN at different temperatures with H2O2. Insights into the emerging characteristics of the modified GCN in photocatalysis were obtained by determining the optical properties, band structure, electrochemical activity and pollutant degradation efficiency. It was found that the introduction of GCN with oxygen functional groups can enhance light absorption and accelerate electron transfer so as to improve the photocatalytic reaction efficiency. The photoinduced reactive radicals and the associated photodegradation were investigated by in situ electron paramagnetic resonance (EPR). The reactive radicals, O2(-) and OH, were responsible for organic degradation. PMID- 26845031 TI - Network Scale Modeling of Lymph Transport and Its Effective Pumping Parameters. AB - The lymphatic system is an open-ended network of vessels that run in parallel to the blood circulation system. These vessels are present in almost all of the tissues of the body to remove excess fluid. Similar to blood vessels, lymphatic vessels are found in branched arrangements. Due to the complexity of experiments on lymphatic networks and the difficulty to control the important functional parameters in these setups, computational modeling becomes an effective and essential means of understanding lymphatic network pumping dynamics. Here we aimed to determine the effect of pumping coordination in branched network structures on the regulation of lymph flow. Lymphatic vessel networks were created by building upon our previous lumped-parameter model of lymphangions in series. In our network model, each vessel is itself divided into multiple lymphangions by lymphatic valves that help maintain forward flow. Vessel junctions are modeled by equating the pressures and balancing mass flows. Our results demonstrated that a 1.5 s rest-period between contractions optimizes the flow rate. A time delay between contractions of lymphangions at the junction of branches provided an advantage over synchronous pumping, but additional time delays within individual vessels only increased the flow rate for adverse pressure differences greater than 10.5 cmH2O. Additionally, we quantified the pumping capability of the system under increasing levels of steady transmural pressure and outflow pressure for different network sizes. We observed that peak flow rates normally occurred under transmural pressures between 2 to 4 cmH2O (for multiple pressure differences and network sizes). Networks with 10 lymphangions per vessel had the highest pumping capability under a wide range of adverse pressure differences. For favorable pressure differences, pumping was more efficient with fewer lymphangions. These findings are valuable for translating experimental measurements from the single lymphangion level to tissue and organ scales. PMID- 26845030 TI - Study protocol: Hybrid Type I cost-effectiveness and implementation study of interpersonal psychotherapy (IPT) for men and women prisoners with major depression. AB - PURPOSE: This article describes the protocol for a Hybrid Type I cost effectiveness and implementation study of interpersonal psychotherapy (IPT) for men and women prisoners with major depressive disorder (MDD). The goal is to promote uptake of evidence-based treatments in criminal justice settings by conducting a randomized effectiveness study that collects implementation data, including a full cost-effectiveness analysis. BACKGROUND: More than 2.3 million people are incarcerated in the United States on any given day. MDD is the most common severe mental illness among incarcerated individuals. Despite the prevalence and consequences of MDD among incarcerated populations, this study will be the first fully-powered randomized trial of any treatment for MDD in an incarcerated population. DESIGN: Given the politically charged nature of the justice system, advantageous health outcomes are often not enough to get an intervention implemented in prisons. To increase the policy impact of this trial, we sought advice from prison providers and administrators about outcomes that would be persuasive to policy-makers and defensible to the public. In this trial, effectiveness questions will be answered using a randomized clinical trial design comparing IPT plus prison treatment as usual (TAU) to TAU alone, with outcomes including depressive symptoms (primary), suicidality, and in prison functioning (enrollment and completion of correctional programs; disciplinary and incident reports; aggression/victimization; social support). Implementation outcomes will include cost-effectiveness; feasibility and acceptability of IPT to clients, providers, and administrators; prison provider intervention fidelity, attitudes, and competencies; and barriers and facilitators of implementation assessed through surveys, interviews, and process notes. PMID- 26845032 TI - Comparing the Effects of Different Smoothing Algorithms on the Assessment of Dimensionality of Ordered Categorical Items with Parallel Analysis. AB - The analysis of polychoric correlations via principal component analysis and exploratory factor analysis are well-known approaches to determine the dimensionality of ordered categorical items. However, the application of these approaches has been considered as critical due to the possible indefiniteness of the polychoric correlation matrix. A possible solution to this problem is the application of smoothing algorithms. This study compared the effects of three smoothing algorithms, based on the Frobenius norm, the adaption of the eigenvalues and eigenvectors, and on minimum-trace factor analysis, on the accuracy of various variations of parallel analysis by the means of a simulation study. We simulated different datasets which varied with respect to the size of the respondent sample, the size of the item set, the underlying factor model, the skewness of the response distributions and the number of response categories in each item. We found that a parallel analysis and principal component analysis of smoothed polychoric and Pearson correlations led to the most accurate results in detecting the number of major factors in simulated datasets when compared to the other methods we investigated. Of the methods used for smoothing polychoric correlation matrices, we recommend the algorithm based on minimum trace factor analysis. PMID- 26845033 TI - A Reduced-Intensity Conditioning Regimen for Patients with Dyskeratosis Congenita Undergoing Hematopoietic Stem Cell Transplantation. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option for progressive marrow failure, myelodysplastic syndrome, or leukemia associated with dyskeratosis congenita (DC). HSCT for DC is limited by a high incidence of treatment-related mortality, thought to be related to underlying chromosomal instability and sensitivity to chemotherapy and radiation. We report our experience in 7 patients with DC who underwent allogeneic transplantation using a reduced-intensity conditioning (RIC) preparative regimen that contained chemotherapy only (no radiation). This RIC regimen, designed specifically for patients with DC, contained alemtuzumab, fludarabine, and melphalan (with melphalan at 50% reduced dosing), with the goal of decreasing toxicity and improving outcome. All 7 patients engrafted, with none developing mixed chimerism or rejection. Two patients experienced acute graft-versus-host disease (GVHD) and 1 went on to develop limited chronic GVHD of the skin. Five patients remain alive and well at a median follow-up of 44 months (range, 14 to 57 months). We conclude that a radiation-free RIC regimen results in durable engraftment, acceptable toxicity, and improved overall survival in patients with DC undergoing allogeneic HSCT. PMID- 26845034 TI - Keep in Mind Quality of Life: Outcome of a Ten-Year Series of Post Transplantation Early Relapses in Childhood Acute Lymphoblastic Leukemia-A Report from the Grand Ouest Oncology Study Group for Children in France. AB - Relapses of acute lymphoblastic leukemia (ALL) early after hematopoietic stem cell transplantations in children are uncommon but associated with a very poor prognosis. Whereas there are no current recommendations for the management of these relapses, the children's quality of life is an important issue. We studied the outcomes, including 1-year overall survival, complete remission, and quality of life, of 19 children with ALL who relapsed within the first year after their transplantation treated in the 5 participating centers between 2000 and 2011 Patients were distributed as follows: supportive care only (group A), outpatient treatment (mainly steroid and vincristine, group B), or intensive inpatient treatment (group C). There were no significant differences in 1-year overall survival (31.5% for the entire cohort) or remission rate for time between transplantation and relapse (< 6 months or 6 to 12 months), transplantation or disease characteristics, or treatment group. However, time spent in hospital (for treatment and complications) significantly differed between treatment groups B and C (20.8% +/- 13.0 versus 59.1% +/- 32.9, respectively; P < .05). No differences in organ toxicities, school attendance, or Lansky scores were found between treatment groups. Our sample size-limited data indicate, in a prepersonalized medicine era, that children treated with steroid and vincristine have the same prognosis as those treated with intensive therapy, but they may benefit from improved quality of life. Nevertheless, new therapeutic strategies are required and future prospective trials would help to establish recommendations. PMID- 26845036 TI - Keep the sick from harm in spontaneous bacterial peritonitis: Dose of beta blockers matters. PMID- 26845037 TI - Reply to 'Is single portal vein perfusion the best approach for machine preservation of liver grafts?'. PMID- 26845039 TI - Limited cooperativity in protein folding. AB - Theory and simulations predict that the structural concert of protein folding reactions is relatively low. Experimentally, folding cooperativity has been difficult to study, but in recent years we have witnessed major advances. New analytical procedures in terms of conformational ensembles rather than discrete states, experimental techniques with improved time, structural, or single molecule resolution, and combined thermodynamic and kinetic analysis of fast folding have contributed to demonstrate a general scenario of limited cooperativity in folding. Gradual structural disorder is already apparent on the unfolded and native states of slow, two-state folding proteins, and it greatly increases in magnitude for fast folding domains. These results demonstrate a direct link between how fast a single-domain protein folds and unfolds, and how cooperative (or structurally diverse) is its equilibrium unfolding process. Reducing cooperativity also destabilizes the native structure because it affects unfolding more than folding. We can thus define a continuous cooperativity scale that goes from the 'pliable' two-state character of slow folders to the gradual unfolding of one-state downhill, and eventually to intrinsically disordered proteins. The connection between gradual unfolding and intrinsic disorder is appealing because it suggests a conformational rheostat mechanism to explain the allosteric effects of folding coupled to binding. PMID- 26845038 TI - Usefulness of a New Three-Dimensional Simulator System for Radiofrequency Ablation. AB - Multipuncture radiofrequency ablation is expected to produce a large ablated area and reduce intrahepatic recurrence of hepatocellular carcinoma; however, it requires considerable skill. This study evaluated the utility of a new simulator system for multipuncture radiofrequency ablation. To understand positioning of multipuncture electrodes on three-dimensional images, we developed a new technology by expanding real-time virtual ultrasonography. We performed 21 experimental punctures in phantoms. Electrode insertion directions and positions were confirmed on computed tomography, and accuracy and utility of the simulator system were evaluated by measuring angles and intersections for each electrode. Moreover, to appropriately assess placement of the three electrodes, puncture procedures with or without the simulator were performed by experts and non experts. Technical success was defined as maximum angle and distance ratio, as calculated by maximum and minimum distances between electrodes. In punctures using 2 electrodes, correlations between angles on each imaging modality were strong (ultrasound vs. simulator: r = 0.991, p<0.001, simulator vs. computed tomography: r = 0.991, p<0.001, ultrasound vs. computed tomography: r = 0.999, p<0.001). Correlations between distances in each imaging modality were also strong (ultrasound vs. simulator: r = 0.993, p<0.001; simulator vs. computed tomography: r = 0.994, p<0.001; ultrasound vs. computed tomography: r = 0.994, p<0.001). In cases with 3 electrodes, distances between each electrode correlated strongly (yellow-labeled vs. red-labeled: r = 0.980, p<0.001; red-labeled vs. blue-labeled: r = 0.953, p<0.001; yellow-labeled vs. blue-labeled: r = 0.953, p<0.001). Both angle and distance ratio (expert with simulator vs. without simulator; p = 0.03, p = 0.02) were significantly smaller in procedures performed by experts using the simulator system. The new simulator system appears to accurately guide electrode positioning. This simulator system could allow multipuncture radiofrequency ablation to be performed more effectively and comfortably. PMID- 26845035 TI - Behavioural Risk Factors in Mid-Life Associated with Successful Ageing, Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review. AB - BACKGROUND: Smoking, alcohol consumption, poor diet and low levels of physical activity significantly contribute to the burden of illness in developed countries. Whilst the links between specific and multiple risk behaviours and individual chronic conditions are well documented, the impact of these behaviours in mid-life across a range of later life outcomes has yet to be comprehensively assessed. This review aimed to provide an overview of behavioural risk factors in mid-life that are associated with successful ageing and the primary prevention or delay of disability, dementia, frailty and non-communicable chronic conditions. METHODS: A literature search was conducted to identify cohort studies published in English since 2000 up to Dec 2014. Multivariate analyses and a minimum follow up of five years were required for inclusion. Two reviewers screened titles, abstracts and papers independently. Studies were assessed for quality. Evidence was synthesised by mid-life behavioural risk for a range of late life outcomes. FINDINGS: This search located 10,338 individual references, of which 164 are included in this review. Follow-up data ranged from five years to 36 years. Outcomes include dementia, frailty, disability and cardiovascular disease. There is consistent evidence of beneficial associations between mid-life physical activity, healthy ageing and disease outcomes. Across all populations studied there is consistent evidence that mid-life smoking has a detrimental effect on health. Evidence specific to alcohol consumption was mixed. Limited, but supportive, evidence was available relating specifically to mid-life diet, leisure and social activities or health inequalities. CONCLUSIONS: There is consistent evidence of associations between mid-life behaviours and a range of late life outcomes. The promotion of physical activity, healthy diet and smoking cessation in all mid-life populations should be encouraged for successful ageing and the prevention of disability and chronic disease. PMID- 26845041 TI - Insulin Stimulates Goose Liver Cell Growth by Activating PI3K-AKT-mTOR Signal Pathway. AB - BACKGROUND/AIMS: Recent studies have suggested a crucial role for PI3K-Akt-mTOR pathway in regulating cell proliferation, so we hypothesize that insulin acts goose hepatocellular growth by PI3K-Akt-mTOR signal pathway. Because the physiological status of liver cells in vitro is different from that in vivo, a simplified cell model in vitro was established. METHODS: Goose primary hepatocytes were isolated and incubated in either no addition as a control or insulin or PI3K-Akt-mTOR pathway inhibitors or co-treatment with glucose and PI3K Akt-mTOR pathway inhibitors; Then, cell DNA synthesis and cell cycle analysis were detected by BrdU-incorporation Assay and Flow cytometric analysis; the mRNA expression and protein expression of factors involved in the cell cycle were determined by Real-Time RT-PCR, ELISA, and western blot. RESULTS: Here we first showed that insulin evidently increased the cell DNA synthesis, the mRNA level and protein content of factors involved in the cell proliferation of goose primary hepatocytes. Meanwhile, insulin evidently increased the mRNA level and protein content of factors involved in PI3K-Akt-mTOR pathway. However, the up regulation of insulin on cell proliferation was decreased significantly by the inhibitors of PBK-Akt-mTOR pathway, LY294002, rapamycin or NVP-BEZ235. CONCLUSION: These findings suggest that PI3K-Akt-mTOR pathway plays an essential role in insulin-regulated cell proliferation of goose hepatocyte. PMID- 26845040 TI - Adiponectin Upregulates MiR-133a in Cardiac Hypertrophy through AMPK Activation and Reduced ERK1/2 Phosphorylation. AB - Adiponectin and miR-133a are key regulators in cardiac hypertrophy. However, whether APN has a potential effect on miR-133a remains unclear. In this study, we aimed to investigate whether APN could regulate miR-133a expression in Angiotensin II (Ang II) induced cardiac hypertrophy in vivo and in vitro. Lentiviral-mediated adiponectin treatment attenuated cardiac hypertrophy induced by Ang II infusion in male wistar rats as determined by reduced cell surface area and mRNA levels of atrial natriuretic peptide (ANF) and brain natriuretic peptide (BNP), also the reduced left ventricular end-diastolic posterior wall thickness (LVPWd) and end-diastolic interventricular septal thickness (IVSd). Meanwhile, APN elevated miR-133a level which was downregulated by Ang II. To further investigate the underlying molecular mechanisms, we treated neonatal rat ventricular myocytes (NRVMs) with recombinant rat APN before Ang II stimulation. Pretreating cells with recombinant APN promoted AMP-activated protein kinase (AMPK) phosphorylation and inhibited ERK activation. By using the inhibitor of AMPK or a lentiviral vector expressing AMPK short hairpin RNA (shRNA) cancelled the positive effect of APN on miR-133a. The ERK inhibitor PD98059 reversed the downregulation of miR-133a induced by Ang II. These results indicated that the AMPK activation and ERK inhibition were responsible for the positive effect of APN on miR-133a. Furthermore, adiponectin receptor 1 (AdipoR1) mRNA expression was inhibited by Ang II stimulation. The positive effects of APN on AMPK activation and miR-133a, and the inhibitory effect on ERK phosphorylation were inhibited in NRVMs transfected with lentiviral AdipoR1shRNA. In addition, APN depressed the elevated expression of connective tissue growth factor (CTGF), a direct target of miR-133a, through the AMPK pathway. Taken together, our data indicated that APN reversed miR-133a levels through AMPK activation, reduced ERK1/2 phosphorylation in cardiomyocytes stimulated with Ang II, revealing a previously undemonstrated and important link between APN and miR-133a. PMID- 26845042 TI - Replication origins: determinants or consequences of nuclear organization? AB - Chromosome replication, gene expression and chromatin assembly all occur on the same template, necessitating a tight spatial and temporal coordination to maintain genomic stability. The distribution of replication initiation events is responsive to local and global changes in chromatin structure and is affected by transcriptional activity. Concomitantly, replication origin sequences, which determine the locations of replication initiation events, can affect chromatin structure and modulate transcriptional efficiency. The flexibility observed in the replication initiation landscape might help achieve complete and accurate genome duplication while coordinating the DNA replication program with transcription and other nuclear processes in a cell-type specific manner. This review discusses the relationships among replication origin distribution, local and global chromatin structures and concomitant nuclear metabolic processes. PMID- 26845044 TI - Masculine and family honor and youth violence: The moderating role of ethnic cultural affiliation. AB - This study examines the involvement in violent behavior of at-risk Arab and Jewish male youth from a large city in Israel. It explores the role masculine and family honor plays in predicting youth involvement in violence and tests whether this association is moderated by ethnic-cultural affiliation. A total of 282 males (59.2% Arab), aged 15-21, filled out a self-report closed-ended questionnaire. We found that among both Jewish and Arab youth a greater concern with masculine honor was positively associated with involvement in violence. We also found that Arab youth are significantly more involved in violent behavior than Jewish youth, and that Arab participants were more concerned with masculine and family honor. However, contrary to what was expected, greater concern with family honor was associated with lower levels of Arab youth involvement in violence. (PsycINFO Database Record PMID- 26845043 TI - Mediating and moderating effects of social support in the study of child abuse and adult physical and mental health. AB - A number of cross-sectional and a few longitudinal studies have shown a developmental relationship between child abuse and adult physical and mental health. Published findings also suggest that social support can lessen the risk of adverse outcomes for some abused children. However, few studies have investigated whether social support mediates or moderates the relationship between child abuse and adult physical and mental health. Structural equation modeling was used to examine data on these topics from a longitudinal study of more than 30 years. While a latent construct of physical and emotional child abuse did not predict adult health outcomes directly, child abuse did predict outcomes indirectly through social support. A test of variable moderation for child abuse and social support was nonsignificant. Results suggest that social support may help explain the association between child abuse and health outcomes at midlife. Implications of the findings for prevention and treatment are discussed. (PsycINFO Database Record PMID- 26845045 TI - Navigating in murky waters: How multiracial Black individuals cope with racism. AB - Multiracial people are often lauded as evidence of the waning significance of race and racism in the United States. In reality, the experiences of multiracial people illuminate the ways that racism still exists and efforts to classify people based on assumed racial characteristics for the purposes of inclusion and exclusion are alive and well. Multiracial individuals experience racism from multiple sources and in various forms, which has the potential to negatively impact their development and well-being. Thus, scholars and practitioners must better understand how the growing population of multiracial individuals learns to cope with such racism. The central aim of this qualitative interview study was to shed light on the ways in which multiracial individuals of African descent in the United States cope with and respond to racism. Findings are organized around 5 broad conceptual themes for coping with and addressing racism: avoidance and internalization, anger and violence, education and advocacy, seeking culture and community, and chameleon identities. Findings of this study speak to the dynamic nature of strategies used to cope with racism and hold implications for practices and programs designed to support positive racial identity development among multiracial individuals of African descent. (PsycINFO Database Record PMID- 26845046 TI - Characteristics, correlates and outcomes of perceived stigmatization in bipolar disorder patients. AB - BACKGROUND: The aim of this study was to elucidate the characteristics, correlates and outcomes of perceived stigmatization in patients with Bipolar Disorder (BD). METHODS: At baseline 50 remitted BD patients completed the Stigma Questionnaire (SQ), the Work and Social Adjustment Scale (WSAS), and the Temperament Evaluation of the Memphis, Pisa, Paris and San Diego Auto Questionnaire - Short Version (TEMPS-A). The BD patients were followed for 24 months as part of their ongoing treatment. Information on illness course and treatments was obtained at baseline and at follow-up through medical records and interviews. RESULTS: The prevalence of perceived stigmatization ranged from 37% to 57% across the areas measured by the SQ. The areas with most perceived stigmatization were work-ability and psychiatric hospitalization. Psychoeducation and affective temperaments emerged as significant independent predictors of perceived stigmatization. Perceived stigmatization was not related to affective recurrences. LIMITATIONS: The follow-up period might have been too short to measure the long-term impact of perceived stigmatization. CONCLUSIONS: The findings suggest that BD patients consider issues concerning work-ability and psychiatric hospitalizations to be particularly affected by stigmatization. Psychoeducation and affective temperaments were, furthermore, identified as factors implicated in perceived stigmatization in this population. PMID- 26845047 TI - The Evaluation and Management of Tall Stature. AB - Tall stature is a common reason for consultation of a paediatric endocrinologist. It is important to always consider underlying pathology. We propose a diagnostic flowchart based on five questions. (1) Does the child have tall stature? (2) Is there evidence of a syndrome? (3) Has there been growth acceleration? (4) Are there signs of puberty? (5) Does the child grow within the target height range? Diagnostic tests can then be ordered targeted to the suspected disorder. The Bayley-Pinneau and Tanner-Whitehouse methods are reasonably accurate in predicting adult height based on bone age in girls, but neither method performs well in boys. Tall stature is not a pathological condition and generally does not need treatment. However, adolescents with a strong treatment wish and their parents should be counselled on the effectivity and safety of available treatments including surgery and high-dose sex steroids. Surgical epiphysiodesis has the advantage that a reasonable height reduction can be achieved at a more advanced bone age, allowing a more accurate adult height prediction to base any treatment decision on. We feel that high-dose oestrogen treatment should no longer be used because of its association with reduced fecundity and imminent ovarian failure. PMID- 26845048 TI - Utilizing Genomics through Family Health History with the Theory of Planned Behavior: Prediction of Type 2 Diabetes Risk Factors and Preventive Behavior in an African American Population in Florida. AB - AIM: African Americans are disproportionately affected by type 2 diabetes. The purpose of this study was to assess to what extent African Americans' knowledge and awareness of family health history and related risk factors for developing type 2 diabetes influence their likelihood of adopting a preventive behavior. METHODS: This study employed an anonymous pencil-and-paper, self-administered survey consisting of two sections. Section 1 was a modified version of the US Surgeon General's Family Health History Initiative and the American Diabetes Association Diabetes Risk Factor Survey. Section 2 of the survey was based on the constructs of the theory of planned behavior. Over 394 African American participants completed the survey. RESULTS: 'Perceived behavioral control' was the strongest predictor of 'likelihood of adopting preventive behavior'. Participants were aware of their family history as a risk factor for type 2 diabetes, but it was not a significant predictor of behavior modifications based on that knowledge. CONCLUSION: The lack of perceived risk in this population shows the importance of not only knowing one's risk factors but translating those risk factors to a more personalized form that fits into the current lifestyle of the individual in a meaningful way. PMID- 26845049 TI - Long working hours and use of psychotropic medicine: a follow-up study with register linkage. AB - OBJECTIVE: This study aimed to investigate the possibility of a prospective association between long working hours and use of psychotropic medicine. METHODS: Survey data drawn from random samples of the general working population of Denmark in the time period 1995-2010 were linked to national registers covering all inhabitants. The participants were followed for first occurrence of redeemed prescriptions for psychotropic medicine. The primary analysis included 25,959 observations (19,259 persons) and yielded a total of 2914 new cases of psychotropic drug use in 99,018 person-years at risk. Poisson regression was used to model incidence rates of redeemed prescriptions for psychotropic medicine as a function of working hours (32-40, 41-48, >48 hours/week). The analysis was controlled for gender, age, sample, shift work, and socioeconomic status. A likelihood ratio test was used to test the null hypothesis, which stated that the incidence rates were independent of weekly working hours. RESULTS: The likelihood ratio test did not reject the null hypothesis (P=0.085). The rate ratio (RR) was 1.04 [95% confidence interval (95% CI) 0.94-1.15] for the contrast 41-48 versus 32-40 work hours/week and 1.15 (95% CI 1.02-1.30) for >48 versus 32-40 hours/week. None of the rate ratios that were estimated in the present study were statistically significant after adjustment for multiple testing. However, stratified analyses, in which 30 RR were estimated, generated the hypothesis that overtime work (>48 hours/week) might be associated with an increased risk among night or shift workers (RR=1.51, 95% CI 1.15-1.98). CONCLUSION: The present study did not find a statistically significant association between long working hours and incidence of psychotropic drug usage among Danish employees. PMID- 26845050 TI - The Artificial Urinary Sphincter in the Management of Incontinence. AB - Despite the emergence of different devices in the treatment of postprostatectomy urinary incontinence, the AMS 800 (American Medical Systems, Minnetonka, MN) remains the gold standard for the treatment of stress urinary incontinence in men. We reviewed the current literature regarding the indications, surgical principles, outcomes, and complications of artificial urinary sphincter placement for stress urinary incontinence after prostatectomy. Despite all the available information, heterogeneous data, different success definitions, and the lack of high-quality prospective studies with long-term follow-up, it is difficult to compare outcomes between studies. In spite of these, the perineal implantation of a single cuff artificial urinary sphincter has withstood the test of time. PMID- 26845052 TI - The Efficacy of Congenital Penile Curvature Repair in Preadolescent Males: Early Outcomes. AB - OBJECTIVE: To characterize the spectrum of congenital penile curvature without hypospadias evaluated at our institution, and to assess the efficacy of surgical repair in prepubescent boys. METHODS: The study group included 82 boys with a diagnosis of congenital penile curvature without hypospadias who elected for surgical repair from 2008 to 2010. We retrospectively reviewed clinical and operative characteristics and recorded surgical outcomes during the length of patients' follow-up at our institution. RESULTS: Of the patients electing surgery, 32 of 82 (39%) underwent penile degloving alone for class I (skin) chordee. Ten of 82 patients (12.2%) required further excision of class II (dysgenic fascial) chordee, and 40 of 82 (48.8%) patients required some combination of techniques to correct varying degrees of class III (dysgenic fascial) chordee. A total of 22.2% of patients returning for follow-up with corporal disproportion had persistent penile curvature compared with 14.3% of boys with fascial chordee and 11.5% of boys with skin chordee. Those children treated with tunical plications and incisions alone fared worse than those children treated with some combination of the Nesbit or modified Nesbit procedure. CONCLUSION: Our study shows not only that the proportion of patients with a hyposplastic urethra may be smaller than previously reported but also that corporal disproportion may be more prevalent. Attention should be paid to this later group as plication without the use of Nesbit techniques may not be enough to ensure an appropriate repair. PMID- 26845051 TI - Pelvic Organ Prolapse Surgery in Academic Female Pelvic Medicine and Reconstructive Surgery Urology Practice in the Setting of the Food and Drug Administration Public Health Notifications. AB - OBJECTIVE: To understand the effect of the Food and Drug Administration (FDA) public health notifications regarding transvaginal placement of surgical mesh for pelvic organ prolapsed (POP) on surgeon practice patterns in tertiary care academic medical centers. MATERIALS AND METHODS: Surgical volume for procedures performed primarily by fellowship trained Female Pelvic Medicine and Reconstructive Surgery at a sampling of 8 academic institutions across the US were collected using current procedural technology codes for POP repair and revision surgeries from 2007 to 2013. SAS statistical software was used to analyze data for trends and to assess differences in number of procedures across years by performing Spearman correlation analysis and Pearson's chi-squared test. Significance of trend was defined as P <.05 for both analysis methods. RESULTS: There has been a substantial reduction in transvaginal mesh-augmented repair of POP since the FDA warning statements of 2008 and 2011. Mesh revision surgery has increased over this same period. However, the total number of interventions for POP has remained stable over the study period. Abdominal sacrocolpopexy has increased as a whole but represents only a small percentage of total cases. CONCLUSION: Surgical correction of POP comprises a large portion of Female Pelvic Medicine and Reconstructive Surgery practice that continues to evolve in the aftermath of the FDA public health notifications. The utilization of transvaginal placement of surgical mesh augmented POP repair has decreased among practicing urologists at a sampling of academic institutions across the United States. Indications for surgery, complications, and outcomes were not evaluated during this retrospective study; however, such data may provide alternative insights into the reasons for the observed trends. PMID- 26845053 TI - Scrotal Cooling to Protect Against Cisplatin-induced Spermatogenesis Toxicity: Preliminary Outcome of an Experimental Controlled Trial. AB - OBJECTIVE: To investigate the protective effects of scrotal cooling on cisplatin induced gonadal toxicity in an animal model. METHODS: Twenty-one male BALB/c mice were divided into 3 groups. The cisplatin group received 2 cycles of cisplatin (2.5 mg/kg/day for 5 days with 16 days of recovery) intraperitoneally, and the cisplatin + cooling group received the same regimen of cisplatin with a cooling protocol: cooling induction for 30 minutes before injection and cooling for 60 minutes after injection. Mice in control group were given an injection of 2 mL normal saline intraperitoneally. After 35 days of recovery (1 cycle of spermatogenesis), the volume of the testes (Cavalieri method), volume density of the tubules and epithelium (point-counting method), and number of cells (optical dissector method) were estimated. RESULTS: The volume of the testes, tubules, and epithelium was reduced between 61% and 66%, and the number of the spermatogonia, spermatocytes, round spermatids, and long spermatids was reduced between 70% and 93% in cisplatin group compared with that of control mice. Cisplatin affected spermatids to a greater extent, and Sertoli cells to a lesser extent than the other cells. The volume and number of the cells were reduced in the cisplatin + cooling group but to a lesser extent compared with those of mice in the cisplatin group. Sertoli cells were more intact in the cisplatin + cooling group compared with those of the control group. CONCLUSION: Scrotal cooling during cisplatin administration seems to have beneficial effects on spermatogenesis. Scrotal cooling may hold promise as a way to protect fertility. PMID- 26845054 TI - Transurethral Resection of the Prostate Biopsy of Suspected Anterior Prostate Cancers Identified by Multiparametric Magnetic Resonance Imaging: A Pilot Study of a Novel Technique. AB - OBJECTIVE: To describe a novel biopsy technique that involves performing a cognitively directed transurethral resection of the prostate (TURP) to diagnose suspected anterior prostate cancers (APCs) detected by multiparametric magnetic resonance imaging (mpMRI) in patients with prior negative transrectal ultrasound (TRUS)-guided biopsies. METHODS: This is a prospective study in which participants aged 50-75 were offered inclusion if they had an elevated prostate specific antigen level, a lesion suspicious for APC on mpMRI, and at least one prior negative TRUS-guided prostate biopsy. Prostatic mpMRI was acquired with a 3 Tesla machine without endorectal coil. Preoperative review of the mpMRI images was used to target the suspected APC on TURP biopsy. The primary outcome was the detection rate of clinically significant prostate cancer, defined as the presence of any Gleason pattern >= 4 in the specimen. Secondary outcomes included biopsy related complications including 30-day readmissions. RESULTS: A total of 16 consecutive participants were enrolled. Median age was 64 years, median prostate specific antigen was 12.4 ng/mL, and participants had a median of 2 prior negative TRUS-guided biopsies. Thirteen (81.3%) participants had clinically significant APCs detected by TURP biopsy. One participant was readmitted within 30-days postprocedure for continuous bladder irrigation. Seven participants (43.8%) underwent radical prostatectomy that confirmed clinically significant disease in all 7 participants. CONCLUSION: Among participants with anterior prostate lesions on mpMRI and prior negative TRUS-guided biopsy, TURP biopsy does detect some clinically significant cancers. This study serves as a proof of concept and further comparative trials are needed prior to widespread adoption. PMID- 26845055 TI - Serum concentrations of TNF-alpha, sTNF-R p55 and p75 and post-traumatic stress in German soldiers. AB - Growing evidence suggests involvement of the tumor necrosis factor (TNF)-alpha system in the pathophysiology of psychiatric disorders. Research into post traumatic stress disorder (PTSD) has investigated serum levels of TNF-alpha, but not to date its soluble receptors sTNF-R p55 and sTNF-R p75. We examined serum levels of TNF-alpha, sTNF-R p55 and sTNF-R p75 in 135 male German soldiers 70 of whom had been deployed abroad and 65 in Germany only. Post-traumatic stress symptoms were measured using the Post-traumatic Stress Diagnostic Scale (PDS) and the Trier Inventory for the Assessment of Chronic Stress (TICS). Correlational analysis controlling for multiple testing, showed no significant Spearman rank correlations between PDS or TICS scores and serum levels of TNF-alpha, sTNF-R p55 or sTNF-R p75, either in the full sample or in the group of soldiers who had been deployed abroad. ANCOVAs showed no significant differences between soldiers with or without a PDS-derived diagnosis of PTSD, or between soldiers with or without deployment abroad, after controlling for age, smoking and body mass index (BMI). These results suggest that the TNF-alpha system, as reflected by TNF-alpha, sTNF R p55 and sTNF-R p75 serum levels, does not play a major role in the pathophysiology and development of PTSD symptoms as measured by the PDS and the TICS. However, several methodological and contextual issues have to be considered. PMID- 26845056 TI - Disease-specific signature of serum miR-20b and its targets IL-8 and IL-25, in myasthenia gravis patients. AB - Myasthenia gravis (MG) is an autoimmune disorder characterized by antibodies directed against components of the neuromuscular junction. Currently, the diagnosis and therapeutic evaluation rely on the serum acetylcholine receptor (AchR) antibody titer, which is not reliable for monitoring. The disruption of the menus had been implicated in many immunological disorders, including MG. A quantitative PCR was used to evaluate the miR-20b level. ELISA was used to determine the levels of IL-8 and IL-25 in serum. Quantitative MG scores (QMGS) were used to examine the clinical manifestations. Here, we report that miR-20b, an immune- and cancer-related miRNA, is decreased in the serum of MG patients and correlates negatively with QMGSs in the pretreatment stage. Furthermore, after treatment with prednisone acetate, levels of miR-20b recover but remain negatively correlated with the QMGS. We also identified that IL-8 and IL-25 are targets of miR-20b via the luciferase reporter system. Both of these are increased in MG and correlate negatively with miR-20b. Furthermore, IL-8 and IL 25 levels are decreased following treatment with prednisone acetate. Our data suggest that miR-20b might be a potential biomarker for MG. PMID- 26845057 TI - MicroRNA-761 is upregulated in hepatocellular carcinoma and regulates tumorigenesis by targeting Mitofusin-2. AB - Hepatocellular carcinoma (HCC) is the sixth most prevalent cancer and the third leading cause of cancer-related deaths worldwide. The fate of a cell is determined by the balance between the processes of fission and fusion that constantly occur in the mitochondria of cells. We previously showed that overexpression of Mitofusin-2 can induce apoptosis in HCC cells by triggering an influx of Ca(2+) into the mitochondria from the ER. The function of Mitofusin-2 has been studied extensively, but the mechanism underlying the post transcriptional regulation of Mitofusin-2 has not been elucidated. In the present study, we aimed to identify the mechanism of Mitofusin-2 regulation in HCC. We demonstrated that Mitofusin-2 is a direct target of miR-761, which was found to be upregulated in HCC tissues. Furthermore, a miR-761 inhibitor impaired mitochondrial function by upregulating Mitofusin-2 and effectively repressed tumor growth and metastasis both in vivo and in vitro. Our findings provide new insight into the mechanism underlying Mitofusin-2 regulation and the potential role of miR-761 in HCC, making it a potential candidate for use in HCC therapy in the future. PMID- 26845059 TI - Electronic Characterization of Reaction Intermediates: The Fluorenylium, Phenalenylium, and Benz[f]indenylium Cations and Their Radicals. AB - Three vibrationally resolved absorption systems commencing at 538, 518, and 392 nm were detected in a 6 K neon matrix after mass-selected deposition of C13 H9 (+) ions (m/z=165) produced from fluorene in a hot-cathode discharge ion source. The benz[f]indenylium (BfI(+) : 538 nm), fluorenylium (FL9(+) : 518 nm), and phenalenylium (PHL(+) : 392 nm) cations are the absorbing molecules. Two electronic systems corresponding to neutral species are apparent at 490 and 546 nm after irradiation of the matrix with lambda<260 nm photons and were assigned to the FL9 and BfI radicals, respectively. The strongest peak at 518 nm is the origin of the 2 (1) B2 <-X (1) A1 absorption of FL9(+) , and the 490 nm band is the 2 (2) A2 <-X (2) B1 origin of FL9. The electronic systems commencing at 538 nm and 546 nm were assigned to the 1 (1) A1 <-X (1) A1 and 1 (2) A2 <-X (2) A2 transitions of BfI(+) and BfI. The 392 nm band is the 1 (1) E'<-X (1) A1 ' transition of PHL(+). The electronic spectra of C13 H9 (+) /C13 H9 were assigned on the basis of the vertical excitation energies calculated with SAC-CI and MS CASPT2 methods. PMID- 26845058 TI - Paired vehicle occupant analysis indicates age and crash severity moderate likelihood of higher severity injury in second row seated adults in frontal crashes. AB - The majority of advances in occupant protection systems for motor vehicle occupants have focused on occupants seated in the front row of the vehicle. Recent studies suggest that these systems have resulted in lower injury risk for front row occupants as compared to those in the second row. However, these findings are not universal. In addition, some of these findings result from analyses that compare groups of front and second row occupants exposed to dissimilar crash conditions, raising questions regarding whether they might reflect differences in the crash rather than the front and second row restraint systems. The current study examines factors associated with injury risk for pairs of right front seat and second row occupants in frontal crashes in the United States using paired data analysis techniques. These data indicate that the occupant seated in the front row frequently experiences the more severe injury in the pair, however there were no significant differences in the rate of occurrence of these events and events where the more severe injury occurs in the second row occupant of the pair. A logistic regression indicated that the likelihood of the more severe injury occurring in the second row seated occupant of the pair increased as crash severity increased, consistent with data from anatomic test dummy (ATD) tests. It also indicated that the second row occupant was more likely to have the more severe injury in the pair if that occupant was the older occupant of the pair. These findings suggest that occupant protection systems which focus on providing protection specifically for injuries experienced by older occupants in the second row in higher severity crash conditions might provide the greatest benefit. PMID- 26845060 TI - Nanomaterial based electrochemical sensors for in vitro detection of small molecule metabolites. AB - Small molecule metabolites secreted by pathological processes can act as molecular biomarkers for clinical diagnosis. In vitro detection of the metabolites such as glucose and reactive oxygen species is of great significance for precise screening, monitoring and prognosis of metabolic disorders and relevant diseases such as cancer, and has been under intense research and development in clinical chemistry and molecular diagnostics. In this review, we summarize recent developments in nanomaterial based electrochemical (bio)sensors for in vitro detection of glucose and reactive oxygen species and the progress in utilizing lightweight and flexible electrodes and micro/nanoscale electrodes for flexible and miniaturized sensors. PMID- 26845061 TI - Sperm processing for advanced reproductive technologies: Where are we today? AB - Assisted reproductive technologies (ARTs) utilize sperm sorting methods to select viable sperm from the semen samples. Conventional sperm sorting techniques in current use are density gradient centrifugation, direct swim-up, and conventional swim-up. These methods use multiple centrifugation steps, which have been shown to generate reactive oxygen species (ROS) that decrease DNA integrity and damage sperm. Newer technologies, such as microfluidics, electrophoresis, motile sperm organelle morphology examination (MSOME), and birefringence eliminate the centrifugation steps and can improve the selection of sperm with higher DNA integrity, normal morphology, and motility as well as improved artificial insemination outcomes. In this review, we discuss some recent research in centrifugation and non-centrifugation based techniques and their effect on sperm quality and ART outcomes. PMID- 26845062 TI - Facilely Tuning Porous NiCo2 O4 Nanosheets with Metal Valence-State Alteration and Abundant Oxygen Vacancies as Robust Electrocatalysts Towards Water Splitting. AB - Great efforts in developing clean electrochemical water splitting technology leads to the rational design and synthesis of highly efficient oxygen evolution reaction (OER) catalysts with low overpotential and fast reaction kinetics. Herein, we focus on the role that morphology and composition play in the OER performance to rationally design freestanding 3D porous NiCo2O4 nanosheets with metal valence states alteration and abundant oxygen vacancies as robust electrocatalysts towards water splitting. Besides metal valence-state alteration, surface modification regarding the evolution of oxygen vacancies is facilely realized upon the sodium borohydride treatment, which is beneficial for the enhanced OER performance. Taking advantage of the porous nanostructures and abundant surface activity sites with high reactivity, the resultant nanostructures exhibit excellent OER activity and stability in alkaline electrolytes that outperform that of pristine NiCo2O4 and commercial RuO2, thus holding great potential for the water splitting. PMID- 26845063 TI - A Longitudinal Regional Educational Model for Pulmonary and Critical Care Fellows Emphasizing Small Group- and Simulation-based Learning. AB - Recent trends have necessitated a renewed focus on how we deliver formal didactic and simulation experiences to pulmonary and critical care medicine (PCCM) fellows. To address the changing demands of training PCCM fellows, as well as the variability in the clinical training, fund of knowledge, and procedural competence of incoming fellows, we designed a PCCM curriculum that is delivered regionally in the Baltimore/Washington, DC area in the summer and winter. The educational curriculum began in 2008 as a collaboration between the Critical Care Medicine Department at the National Institutes of Health and the Pulmonary and Critical Care Section of the Department of Medicine at MedStar Washington Hospital Center and now includes 13 individual training programs in PCCM, critical care medicine, and pulmonary diseases in Baltimore and Washington, DC. Informal and formal feedback from the fellows who participated led to substantial changes to the course curriculum, allowing for continuous improvement. The educational consortium has helped build a local community of educators to share ideas, support each other's career development, and collaborate on other endeavors. In this article, we describe how we developed and deliver this curriculum and report on lessons learned. PMID- 26845065 TI - Substrate Activity Screening (SAS) and Related Approaches in Medicinal Chemistry. AB - Substrate activity screening (SAS) was presented a decade ago by Ellman and co workers as a straightforward methodology for the identification of fragment-sized building blocks for enzyme inhibitors. Ever since, SAS and variations derived from it have been successfully applied to the discovery of inhibitors of various families of enzymatically active drug targets. This review covers key achievements and challenges of SAS and related methodologies, including the modified substrate activity screening (MSAS) approach. Special attention is given to the kinetic and thermodynamic aspects of these methodologies, as a thorough understanding thereof is crucial for successfully transforming the identified fragment-sized hits into potent inhibitors. PMID- 26845064 TI - Role of voltage-gated calcium channels in the regulation of aldosterone production from zona glomerulosa cells of the adrenal cortex. AB - Zona glomerulosa cells (ZG) of the adrenal gland constantly integrate fluctuating ionic, hormonal and paracrine signals to control the synthesis and secretion of aldosterone. These signals modulate Ca2+ levels, which provide the critical second messenger to drive steroid hormone production. Angiotensin II is a hormone known to modulate the activity of voltage-dependent L- and T-type Ca2+ channels that are expressed on the plasma membrane of ZG cells in many species. Because the ZG cell maintains a resting membrane voltage of approximately -85 mV and has been considered electrically silent, low voltage-activated T-type Ca2+ channels are assumed to provide the primary Ca2+ signal that drives aldosterone production. However, this view has recently been challenged by human genetic studies identifying somatic gain-of-function mutations in L-type CaV 1.3 channels in aldosterone-producing adenomas of patients with primary hyperaldosteronism. We provide a review of these assumptions and challenges, and update our understanding of the state of the ZG cell in a layer in which native cellular associations are preserved. This updated view of Ca2+ signalling in ZG cells provides a unifying mechanism that explains how transiently activating CaV 3.2 channels can generate a significant and recurring Ca2+ signal, and how CaV 1.3 channels may contribute to the Ca2+ signal that drives aldosterone production. PMID- 26845066 TI - Quantitative Evaluation of Cancer Cell Adhesion to Self-Assembled Monolayer Patterned Substrates by Reflection Interference Contrast Microscopy. AB - Adhesion of cancer cells with different metastatic potential and anticancer drug resistance has been quantitatively evaluated by using self-assembled monolayer (SAM)-patterned substrates and reflection interference contrast microscopy (RICM). Cell-adhesive SAM spots with optimized diameter could prevent cell-cell adhesion and thus allowed the systematic evaluation of statistically reliable numbers of contact area between single cancer cells and substrates by RICM. The statistical image analysis revealed that highly metastatic mouse melanoma cells showed larger contact area than lowly metastatic cells. We also found that both cancer cell types exhibited distinct transition from the "strong" to "weak" adhesion states with increase in the concentration of (-)-epigallocatechin gallate (EGCG), which is known to exhibit cancer preventive activity. Mathematical analysis of the adhesion transition revealed that adhesion of the highly metastatic mouse melanoma cells showed more EGCG tolerance than that of lowly metastatic cells. Moreover, time-lapse RICM observation revealed that EGCG weakened cancer cell adhesion in a stepwise manner, probably via focal adhesion complex. These results clearly indicate that contact area can be used as a quantitative measure for the determination of cancer phenotypes and their drug resistance, which will provide physical insights into the mechanism of cancer metastasis and cancer prevention. PMID- 26845067 TI - Downfield-NOE-suppressed amide-CEST-MRI at 7 Tesla provides a unique contrast in human glioblastoma. AB - PURPOSE: The chemical exchange saturation transfer (CEST) effect observed in brain tissue in vivo at the frequency offset 3.5 ppm downfield of water was assigned to amide protons of the protein backbone. Obeying a base-catalyzed exchange process such an amide-CEST effect would correlate with intracellular pH and protein concentration, correlations that are highly interesting for cancer diagnosis. However, recent experiments suggested that, besides the known aliphatic relayed-nuclear Overhauser effect (rNOE) upfield of water, an additional downfield rNOE is apparent in vivo resonating as well around +3.5 ppm. In this study, we present further evidence for the underlying downfield-rNOE signal, and we propose a first method that suppresses the downfield-rNOE contribution to the amide-CEST contrast. Thus, an isolated amide-CEST effect depending mainly on amide proton concentration and pH is generated. METHODS: The isolation of the exchange mediated amide proton effect was investigated in protein model-solutions and tissue lysates and successfully applied to in vivo CEST images of 11 glioblastoma patients. RESULTS: Comparison with gadolinium contrast enhancing longitudinal relaxation time-weighted images revealed that the downfield-rNOE-suppressed amide-CEST contrast forms a unique contrast that delineates tumor regions and show remarkable overlap with the gadolinium contrast enhancement. CONCLUSION: Thus, suppression of the downfield rNOE contribution might be the important step to yield the amide proton CEST contrast originally aimed at. Magn Reson Med 77:196-208, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26845068 TI - Discharge timeliness and its impact on hospital crowding and emergency department flow performance. AB - OBJECTIVE: The objective of this research is to identify optimal inpatient discharge time targets to help hospitals reduce crowding, improve patient flow through the ED and balance staff workload. METHODS: Fifteen months of emergency and inpatient records from a large quaternary teaching hospital were used to reconstruct patient pathways from hospital presentation to discharge. Discrete event simulation was used to assess operationally realistic discharge scenarios on flow performance. Main output measures included National Emergency Access Target (NEAT) performance (an ED performance metric), time spent waiting for a bed, hospital length of stay (LOS) and occupancy. RESULTS: Similar levels of improvement in NEAT performance (16%), and reductions in average bed occupancy (1.5%) and inpatient bed wait time (25%) were observed across the simulation that discharged 80% patients before 11 a.m. and one that spread the target between 10 a.m. and 2 p.m. Individual inpatient wards returned potential improvements in NEAT performance (median 10%, interquartile range (IQR) 7%), and reductions in hospital LOS (median 1%, IQR 1%) and average occupancy (median 1%, IQR 2%) across the discharge scenarios. CONCLUSIONS: Conventional discharge targets like '80% by 11 a.m.' and others that spread targets across the day to balance staff workload freed up the equivalent of nine available beds for incoming patient flow, significantly reducing time spent waiting for an inpatient bed, hospital LOS and occupancy, and delivering much needed improvements in NEAT performance. While different strategies and workload distributions may suit individual hospital services, the study makes a strong case for improving 'early in the day' discharge timeliness to deliver better ED flow. PMID- 26845070 TI - Gas-Phase Reactions of Methoxyphenols with NO3 Radicals: Kinetics, Products, and Mechanisms. AB - Methoxyphenols, a group of important tracers for wood smoke, are emitted to the atmosphere in large quantities, but their transformations are rarely studied. In this study, the kinetics and products of the gas-phase reactions of eugenol and 4 ethylguaiacol with NO3 radicals were investigated online using a vacuum ultraviolet photoionization gas time-of-flight mass spectrometer. The rate coefficients of the gaseous reactions of eugenol and 4-ethylguaiacol with NO3 radicals were (1.6 +/- 0.4) * 10(-13) and (1.1 +/- 0.2) * 10(-12) cm(3) molecule( 1) s(-1) (at 298 K), indicating that the atmospheric lifetimes of the NO3 radicals were 3.5 and 0.5 h, respectively. With the aid of gas-chromatography mass-spectrometry analysis, several types of degradation products were identified with nitro derivatives as the major products. The configurations of the nitro product isomers and their formation mechanisms were determined via theoretical calculations. On the basis of these products, degradation pathways of the methoxyphenols with NO3 radicals were proposed. This study determines the degradation rates and mechanisms of the methoxyphenols at night and implies the significant NO3 nighttime chemistry. PMID- 26845069 TI - Distinct neural mechanisms for remembering when an event occurred. AB - Events are often remembered as having occurred in a specific order, but almost nothing is known about how the brain encodes this temporal information. It is commonly assumed that temporal information is encoded via a single mechanism, based either on the temporal context in which the event occurred or inferred from the strength of the memory trace itself. By analyzing time-dependent changes in activity patterns, we show that the distinctiveness of contextual representations in the hippocampus and anterior and medial prefrontal cortex was associated with accurate recency memory. In contrast, overall activation in the perirhinal and lateral prefrontal cortices predicted whether an object would be judged more recent, regardless of accuracy. These results demonstrate that temporal information was encoded through at least two complementary neural mechanisms. PMID- 26845073 TI - Impaired Neurite Contact Guidance in Ubiquitin Ligase E3a (Ube3a)-Deficient Hippocampal Neurons on Nanostructured Substrates. AB - Recent discoveries indicate that during neuronal development the signaling processes that regulate extracellular sensing (e.g., adhesion, cytoskeletal dynamics) are important targets for ubiquitination-dependent regulation, in particular through E3 ubiquitin ligases. Among these, Ubiquitin E3a ligase (UBE3A) has a key role in brain functioning, but its function and how its deficiency results in the neurodevelopmental disorder Angelman syndrome is still unclear. Here, the role of UBE3A is investigated in neurite contact guidance during neuronal development, in vitro. The microtopography sensing of wild-type and Ube3a-deficient hippocampal neurons is studied by exploiting gratings with different topographical characteristics, with the aim to compare their capabilities to read and follow physical directional stimuli. It is shown that neuronal contact guidance is defective in Ube3a-deficient neurons, and this behavior is linked to an impaired activation of the focal adhesion signaling pathway. Taken together, the results suggest that the neuronal contact sensing machinery might be affected in Angelman syndrome. PMID- 26845074 TI - Reduced NF-kappaB activity is observed in dermal fibroblasts from black-skinned African individuals. PMID- 26845075 TI - Anti-Fogging/Self-Healing Properties of Clay-Containing Transparent Nanocomposite Thin Films. AB - Highly transparent antifogging films were successfully prepared on various substrates, including glass slides, silicon, copper and PMMA, by spin-coating a mixture of polyvinylpyrrolidone and aminopropyl-functionalized, nanoscale clay platelets. The resulting films were superhydrophilic and showed more than 90% transmission of visible light, as well as excellent antifogging and self-healing properties. PMID- 26845076 TI - Improved cell infiltration of electrospun nanofiber mats for layered tissue constructs. AB - While achieving the spatial organization of cells within 3D assembled nanofiber/cell constructs via nanofiber-enabled cell layering, the small sizes of inter-fiber pores of the electrospun nanofiber mats could significantly limit cell penetration across the layers for rapid formation of an integrated tissue construct. To address this challenge, efforts were made to improve cell infiltration of electrospun nanofiber mats by modulating the density distribution and spatial organization of the fibers during electrospinning. Collection of collagen-containing electrospun nanofibers (300-600 nm in diameter) onto the surface of a stainless steel metal mesh (1 mm * 1 mm in mesh size) led to the periodic alternation of fiber density from densely packed to loosely arranged distribution within the same mat, in which the densely packed fibers maintained the structural integrity while the region of loose fibers allowed for cell penetration. Along with improved cell infiltration, the distinct fiber organization between dense and loose fiber regions also induced different morphology of fibroblasts (stellate vs. elongated spindle-like). Assembly of cell seeded nanofiber sheets into 3D constructs with such periodically organized nanofiber mats further demonstrated their advantages in improving cell penetration across layers in comparison to either random or aligned nanofiber mats. Taken together, modulation of nanofiber density to enlarge the pore size is effective to improve cell infiltration through electrospun mats for better tissue formation. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1479 1488, 2016. PMID- 26845077 TI - Teaching hospital cataract surgical outcomes in Adelaide, Australia. PMID- 26845078 TI - Characterization of relaxant mechanism of H2 S in mouse corpus cavernosum. AB - The aim of this study was to investigate the mechanism of H2 S-induced relaxation in mouse corpus cavernosal tissue. l-cysteine (10(-6) * 10(-3) mol/L) and exogenous H2 S (NaHS; 10(-6) to 10(-3) mol/L) induced concentration-dependent relaxation. l-cysteine-induced relaxations was reduced by d,l-propargylglycine, a cystathionine gamma lyase (CSE) inhibitor but not influenced by aminooxyacetic acid, a cystathionine beta synthase (CBS) inhibitor. l-cysteine induced relaxations, but not of those of H2 S diminished in endothelium-denuded tissues. N(omega) -nitro-l-arginine (l-NA; 10(-4) mol/L), a nitric oxide synthase inhibitor, and ODQ (10(-4) mol/L), a guanylyl cyclase inhibitor, increased the H2 S-induced relaxation. Zaprinast (5 * 10(-6) mol/L) and sildenafil (10(-6) mol/L), phosphodiesterase inhibitors, inhibited H2 S-induced relaxation. Adenylyl cyclase inhibitors N-ethylmaleimide (2.5 * 10(-5) mol/L) and SQ22536 (10(-4) mol/L) reduced relaxation to H2 S. Also, H2 S-induced relaxation was reduced by KCl (50 mmol/L), 4-aminopyridine (10(-3) mol/L), a Kv inhibitor, glibenclamide (10(-5) mol/L), a KATP inhibitor or barium chloride (10(-5) mol/L), a KIR inhibitor. However, H2 S-induced relaxation was not influenced by apamin (10(-6) mol/L), a SKC a (2+) inhibitor, charybdotoxin (10(-7) mol/L), an IKC a (2+) and BKC a (2+) inhibitor or combination of apamin and charybdotoxin. Nifedipine (10(-6) mol/L), an L-type calcium channel blocker and atropine (10(-6) mol/L), a muscarinic receptor blocker, inhibited H2 S-induced relaxation. However, H2 S-induced relaxation was not influenced by ouabain (10(-4) mol/L), a Na(+) /K(+) -ATPase inhibitor. This study suggests that H2 S endogenously synthesizes from l-cysteine by CSE endothelium-dependent in mouse corpus cavernosum tissue, and exogenous H2 S may cause endothelium-independent relaxations via activation of K channels (KATP channel, KV channels, KIR channels), L-type voltage-gated Ca(2+) channels, adenylyl cyclase/cAMP pathway and muscarinic receptor, and there is the interaction between H2 S and NO/cGMP. PMID- 26845079 TI - Gas-Phase Dopant-Induced Conformational Changes Monitored with Transversal Modulation Ion Mobility Spectrometry. AB - The potential of a Transversal Modulation Ion Mobility Spectrometry (TMIMS) instrument for protein analysis applications has been evaluated. The Collision Cross Section (CCS) of cytochrome c measured with the TMIMS is in agreement with values reported in the literature. Additionally, it enables tandem IMS-IMS prefiltration in dry gas and in vapor doped gas. The chemical specificity of the different dopants enables interesting studies on the structure of proteins as CCS changed strongly depending on the specific dopant. Hexane produced an unexpectedly high CCS shift, which can be utilized to evaluate the exposure of hydrophobic parts of the protein. Alcohols produced higher shifts with a dual behavior: an increase in CCS due to vapor uptake at specific absorption sites, followed by a linear shift typical for unspecific and unstable vapor uptake. The molten globule +8 shows a very specific transition. Initially, its CCS follows the trend of the compact folded states, and then it rapidly increases to the levels of the unfolded states. This strong variation suggests that the +8 charge state undergoes a dopant-induced conformational change. Interestingly, more sterically demanding alcohols seem to unfold the protein more effectively also in the gas phase. This study shows the capabilities of the TMIMS device for protein analysis and how tandem IMS-IMS with dopants could provide better understanding of the conformational changes of proteins. PMID- 26845080 TI - Reply. PMID- 26845081 TI - Pyrrole as a Directing Group: Regioselective Pd(II)-Catalyzed Alkylation and Benzylation at the Benzene Core of 2-Phenylpyrroles. AB - Pyrrole has been employed for the first time as a directing group in the Pd(II) catalyzed ortho-functionalization of C(sp(2))-H bonds. A variety of substituted 2 phenylpyrroles were successfully methylated, alkylated, or benzylated in the ortho-position of the benzene ring, yielding the respective 2-substituted pyrrol 2-yl benzenes (36 examples, 51-93% yield). Neither additives nor additional ligands were required to perform the reaction, which was routinely conducted with PdBr2 as the catalyst and Li2CO3 as the base. Mechanistically, there is evidence that precoordination of palladium to the pyrrole enables the regioselective ortho attack. PMID- 26845083 TI - Reply to "Comment on 'Metal Semiconductor Field-Effect Transistor with MoS2/Conducting NiOx van der Waals Schottky Interface for Intrinsic High Mobility and Photoswitching Speed'". PMID- 26845082 TI - All the O2 Consumed by Thermus thermophilus Cytochrome ba3 Is Delivered to the Active Site through a Long, Open Hydrophobic Tunnel with Entrances within the Lipid Bilayer. AB - Cytochrome ba3 is a proton-pumping heme-copper oxygen reductase from the extreme thermophile Thermus thermophilus. Despite the fact that the enzyme's active site is buried deep within the protein, the apparent second order rate constant for the initial binding of O2 to the active-site heme has been experimentally found to be 10(9) M(-1) s(-1) at 298 K, at or near the diffusion limit, and 2 orders of magnitude faster than for O2 binding to myoglobin. To provide quantitative and microscopic descriptions of the O2 delivery pathway and mechanism in cytochrome ba3, extensive molecular dynamics simulations of the enzyme in its membrane embedded form have been performed, including different protocols of explicit ligand sampling (flooding) simulations with O2, implicit ligand sampling analysis, and in silico mutagenesis. The results show that O2 diffuses to the active site exclusively via a Y-shaped hydrophobic tunnel with two 25-A long membrane-accessible branches that coincide with the pathway previously suggested by the crystallographically identified xenon binding sites. The two entrances of the bifurcated tunnel of cytochrome ba3 are located within the lipid bilayer, where O2 is preferentially partitioned from the aqueous phase. The largest barrier to O2 migration within the tunnel is estimated to be only 1.5 kcal/mol, allowing O2 to reach the enzyme active site virtually impeded by one-dimensional diffusion once it reaches a tunnel entrance at the protein surface. Unlike other O2-utilizing proteins, the tunnel is "open" with no transient barriers observed due to protein dynamics. This unique low-barrier passage through the protein ensures that O2 transit through the protein is never rate-limiting. PMID- 26845084 TI - Predicting the Risk of Clostridium difficile Infection upon Admission: A Score to Identify Patients for Antimicrobial Stewardship Efforts. AB - INTRODUCTION: Increasing morbidity and health care costs related to Clostridium difficile infection (CDI) have heightened interest in methods to identify patients who would most benefit from interventions to mitigate the likelihood of CDI. OBJECTIVE: To develop a risk score that can be calculated upon hospital admission and used by antimicrobial stewards, including pharmacists and clinicians, to identify patients at risk for CDI who would benefit from enhanced antibiotic review and patient education. METHODS: We assembled a cohort of Kaiser Permanente Northwest patients with a hospital admission from July 1, 2005, through December 30, 2012, and identified CDI in the six months following hospital admission. Using Cox regression, we constructed a score to identify patients at high risk for CDI on the basis of preadmission characteristics. We calculated and plotted the observed six-month CDI risk for each decile of predicted risk. RESULTS: We identified 721 CDIs following 54,186 hospital admissions-a 6-month incidence of 13.3 CDIs/1000 patient admissions. Patients with the highest predicted risk of CDI had an observed incidence of 53 CDIs/1000 patient admissions. The score differentiated between patients who do and do not develop CDI, with values for the extended C-statistic of 0.75. Predicted risk for CDI agreed closely with observed risk. CONCLUSION: Our risk score accurately predicted six-month risk for CDI using preadmission characteristics. Accurate predictions among the highest-risk patient subgroups allow for the identification of patients who could be targeted for and who would likely benefit from review of inpatient antibiotic use or enhanced educational efforts at the time of discharge planning. PMID- 26845085 TI - Stark Effect Spectroscopy of Mono- and Few-Layer MoS2. AB - We demonstrate electrical control of the A-exciton interband transition in mono- and few-layer MoS2 crystals embedded into photocapacitor devices via the DC Stark effect. Electric field-dependent low-temperature photoluminescence spectroscopy reveals a significant tuneability of the A-exciton transition energy up to ~ 16 meV from which we extract the mean DC exciton polarizability ?betaN? = (0.58 +/- 0.25) * 10(-8) Dm V(-1). The exciton polarizability is shown to be layer independent, indicating a strong localization of both electron and hole wave functions in each individual layer. PMID- 26845087 TI - Misdiagnosis of Behcet Disease: Should We Examine the Patient's Tongue? PMID- 26845089 TI - Ridge Expansion by Flapless Split Crest and Immediate Implant Placement: Evolution of the Technique. AB - Various treatment strategies and techniques have been proposed to perform alveolar bone augmentation; most common are guided bone regeneration, split crest, and autologous bone grafting. All of these techniques are reported to possess bone regenerative properties of osteoinduction and osteoconduction in relation to regenerated bone survival. Split crest resulted to be one of the most reliable bone augmentation techniques. In this study, we describe a new flapless modified split crest technique on 4 patients to optimize the bone regeneration with bone augmentation implant insertion in 1 single stage. The rationale of this technique is to obtain a proper buccal cortex expansion preserving its vascular supply and avoiding periosteal elevation for better cortical bone preservation. The main advantages of this technique consist in a single surgical stage without donor sites, vascular periosteal preservation of vestibular cortical walls, preservation of alveolar bone height avoiding bone loss after implant kit drilling, and preservation of proper cortical thickness on both sides, thereby saving periosteal nourishment on the vestibular side. Indication for this technique could be extended to almost every implant insertion for alveolar height saving at drilling time for implant insertion, because of the alveolar crest shape. PMID- 26845090 TI - Evaluation of Oxygen Saturation and Heart Rate During Intraoral Impression Taking in Infants With Cleft Lip and Palate. AB - OBJECTIVE: The aim of the study was to evaluate the changes in oxygen saturation and heart pulse during intraoral impression taking from infants with cleft lip and palate (CLP) at onset of presurgical orthopedic therapy. SUBJECTS AND METHODS: In our study, 21 uni- and bilateral infants with CLP (9 female, 12 males, mean age 5.90 +/- 2.46 days) were monitored and heart pulse and oxygen saturation were measured under operating conditions before any intervention (T1), after delivery of 50% supplemental oxygen (T2), during impression taking with oxygen support (T3), and immediately before the discharge from the operating room (T4). RESULTS: Statistically significant differences were found in the average oxygen saturation levels (P < 0.01), but not in heart rates (P > 0.05) between T1, T2, T3, and T4. Decreases in the oxygen levels from T2 to T3 were noted (P < 0.01). Overall, oxygen levels increased from T1 to T4 (P < 0.01). CONCLUSIONS: Oxygen saturation levels may decrease during intraoral impression taking in infants with CLP despite the supplemental oxygen under operating conditions. No changes in the heart rate during the procedure showed that the cardiac output was sufficient, whereas the decrease in oxygen saturation demonstrated hypoventilation because of the anatomic structure and impression-taking process. It may be advised that the impression should be taken under the supervision of the anesthetist, with monitoring of, and supplying oxygen to, the infant with CLP. PMID- 26845091 TI - Swiveling a Single Expanded Forehead Flap: A Novel Effective Economical Approach to Total Bilateral Upper and Lower Eyelid Reconstruction. AB - In our novel approach, a single expanded forehead flap was used to reconstruct bilateral upper and lower eyelids in orbital trauma. A 40-year-old man sustained blast injury resulting in bilateral orbital exenteration and need for bilateral socket and eyelid reconstruction. The sockets were each resurfaced with a temporalis flap. A subgaleal forehead tissue expander was expanded during several weeks until enough tissue was obtained. The single expanded forehead flap was swiveled in stages to reconstruct both upper and lower eyelids beginning with the left eye then the right. With this method, the authors recreated the bilateral upper and lower eyelids with a single pedicled flap and ensured secure retention of prostheses to give an acceptable appearance. The novel approach of swiveling a single expanded pedicled forehead flap to reconstruct bilateral upper and lower eyelids is easy and effective providing adequate like for like autologous tissue, and economical requiring only 1 donor site. PMID- 26845086 TI - Sequestering survivin to functionalized nanoparticles: a strategy to enhance apoptosis in cancer cells. AB - Survivin belongs to the family of inhibitor of apoptosis proteins (IAP) and is present in most cancers while being below detection limits in most terminally differentiated adult tissues, making it an attractive protein to target for diagnostic and, potentially, therapeutic roles. Sub-100 nm poly(propargyl acrylate) (PA) particles were surface modified through the copper-catalyzed azide/alkyne cycloaddition of an azide-terminated survivin ligand derivative (azTM) originally proposed by Abbott Laboratories and speculated to bind directly to survivin (protein) at its dimer interface. Using affinity pull-down studies, it was determined that the PA/azTM nanoparticles selectively bind survivin and the particles can enhance apoptotic cell death in glioblastoma cell lines and other survivin over-expressing cell lines such as A549 and MCF7 relative to cells incubated with the original Abbott-derived small molecule inhibitor. PMID- 26845092 TI - The Coexistence of Rathke Cleft Cyst and Pituitary Adenoma. AB - Both of Pituitary adenoma (PA) and Rathke cleft cyst (RCC) are the most common and benign sellar lesions. Generally, the origin of RCC is considered to be derived from remnants of Rathke punch, while PA is formed by proliferation of the anterior wall of Rathke pouch. Although they have a possibility to share a common embryological origin, the coexistence of PA and RCC is extremely rare. Here, the authors report a 50-year-old male patient who was found to have a large cystic sellar lesion, and surgical resection revealed components of a RCC coexisting with a PA. This collision reminded us of the possibility of RCC coexisting with PA. Furthermore, a clinicopathologic relation of them were reviewed and investigated. PMID- 26845093 TI - Coexistence of Wormian Bones With Metopism, and Vice Versa, in Adult Skulls. AB - OBJECTIVE: The aim of the study is to investigate coexistence of Wormian bones with metopism, and vice versa, in adult skulls. MATERIALS AND METHODS: A total of 160 dry adult human skulls of unknown sex and ages were randomly selected from the Gross Anatomy Laboratory of Medical School of Dokuz Eylul University. The skulls were examined for presence of metopism, Wormian bones (WB), and coexistence of WBs with metopism and vice versa. Topographic distribution of the WBs was macroscopically evaluated within the skulls including metopism. The photographs were being taken with Canon 400B (55 mm objective). RESULTS: The frequency of metopism and WBs in 160 skulls is 7.50% (12/160) and 59.3% (95/160), respectively, P < 0.05 (). The incidence of coexistence of WBs with metopism was found as 11 of 12 skulls (91.66%), whereas the incidence of coexistence of metopism with WBs was found as 11 of 95 skulls (11.58%), P < 0.05 (). There were totally 23 sutures including WBs in 11 skulls, which had metopism (). The number (%) of metopic skulls for each specific suture including WBs were found as: 11 lamdoid sutures in 7/11 (63.63%) skulls, 4 lambda in 4/11 (36.36%) skulls, 2 asterion in 2/11 (18.18%) skulls, 1 squamous in 1/11 (9.09%) skull, 2 sagittal in 2/11 (18.18%) skulls, and 3 parieromsatoid sutures in 2/11 (18.18%) skulls (). The distribution of these 23 WBs in sutures of 11 skulls including metopisms is determined as follows: 11/23 (47.82%) WBs at lambdoid sutures [5/23 (21.74%) at the right lambdoid sutures and 6/23 (26.08%) at the left lambdoid sutures, and 4 pair of 11 WBs bilaterally located]; 4 (17.39%) WBs at lambda; 2/23 (8.69%) WBs at asterion [1/23 (4.34%) at the right asterion and 1/23 (4.34%) at the left asterion of 2 diverse skulls]; 2/23 (8.69%) WBs at sagittal sutures; 1/23 (4.34%) WBs at the left squamous suture; 3/23 (13.04%) WBs at parietomastoid sutures [2/23 (8.69%) at the right parietomastoid sutures and 1/23 (4.34%) at the left parietomastoid suture and 1 pair of them bilaterally located; , ].(Figure is included in full-text article.)(Table is included in full-text article.)(Table is included in full-text article.) CONCLUSIONS: : There was a significant difference in rates between coexistence of WBs with metopism (11/12, 91.66%) and coexistence of metopism with WBs (11/95, 11.58%). The factors leading to metopism may also lead to WBs, whereas that the factors leading to WBs may not lead to metopism. PMID- 26845094 TI - Shape and Height of Tarsal Plates. AB - The aim of this study is to elucidate the anatomic detail of the shape and height of the tarsal plates in Koreans.Fifty-four eyelids from Korean adult cadavers were used. Skin, subcutaneous tissue, and the orbicularis oculi muscle were all removed and the tarsal plates were exposed. The shapes of the tarsal plates were observed and the vertical heights of the tarsal plates were measured at its 1/4 (medial), 2/4 (central), and 3/4 (lateral) horizontal length.Tarsal plates were semilunar shaped and classified into 3 types: symmetric, medially skewed, and laterally skewed. For the upper eyelids, the laterally skewed type was the most frequent (42, 77.8%), followed by the medially skewed (8, 14.9%), and symmetric (4, 7.4%). For the lower eyelids, the laterally skewed type (20, 36.7%), the medially skewed (18, 33.3%), and symmetric type (16, 30.0%) had similar ratios. The vertical height of the upper tarsal plate was greatest at the central point (9.3 +/- 0.9 mm), followed by the lateral point (7.1 +/- 1.0 mm), and the medial point (6.2 +/- 0.8 mm). The height of the lower tarsal plate was also greatest at the central point (4.6 +/- 0.6 mm), followed by the medial point (3.9 +/- 0.5 mm), and the lateral point (3.8 +/- 0.5 mm). The base-height ratio of the upper tarsal plate was approximately 7:3 (2.344).Caucasians have wider (25-30 mm) and higher (10-12 mm) upper tarsal plates than those of Asians (21.8 mm, 9.3 mm). The vertical height of the lower tarsal plate, however, is similar both in Caucasians (4-5 mm) and in Asians (4.6 mm). Our results would be helpful for supratarsal fixation in Asian blepharoplasties. PMID- 26845095 TI - Functional Assessments in Patients Undergoing Radial Forearm Flap Following Hemiglossectomy. AB - Our goal was to evaluate the functional outcomes following radial forearm free flap reconstruction with a focus on radiotherapy. A 2-year prospective study was performed. A total of 47 patients were enrolled finally. They were asked to complete the swallowing, chewing, speech domains of the University of Washington Quality of Life questionnaire preoperatively and at 2 years postoperatively. Swallowing capacity was apparently affected after surgery, but no patients reported there was chokes cough during eating, the mean score was 51.1 (SD: 21.3). Most patients (70.2%) presented their articulation was good enough for everyday life, and the mean score was 60.0 (SD: 21.1). As for chewing, only 7 (14.9%) patients complained there was negative effect, and the mean score was as high as 92.6 (SD: 18.0). Compared to patients with surgery only, patients with postoperative radiotherapy only had significantly worse swallowing and speech capacity. Compared with patients with postoperative radiotherapy only, patients with both preoperative and postoperative radiotherapy tended to have better swallowing and speech. No significant differences were found between chewing and radiotherapy. In most patients, the results of swallowing, speech, and chewing are favorable. Postoperative radiotherapy has an apparent impact on functional impairment, but preoperative tends to preserve the original tongue function. PMID- 26845096 TI - A New Designed Expander Supported by Spike Miniscrews With Enhanced Stability. AB - INTRODUCTION: This article represents a new design of expander-spike expander-to correct transverse maxillary deficiency. This new type appliance is easy to fabricate, more hygienic, and less soft-tissue irritation because of elimination of acrylic plate. In addition, because of the position of mini-implant, it can provide a relatively parallel alveolar expansion, compared with other types of expander. MATERIALS AND METHODS: The spike expander consists of 2 parts: 4 spike screws and an expansion screw. Four spike screws were placed on the palatal slope. After installation of the spike screws, based on the position of spike screw, the extension arms of expansion screw were bended on the cast model, and connected to the spike screws by adding resin. The expansion screw was turned once a day (0.25 mm/d), and the process was terminated at 6 weeks. RESULTS: The stability and design of the spike screw enable widening of maxilla easier. Compared with other expander, spike expander reduces the forces being placed directly on teeth, which can maximize skeletal expansion, minimize dental tipping, produce a relatively parallel expansion, and reduce soft-tissue irritation caused by acrylic pads. Furthermore, the teeth can be aligned and leveled simultaneously using the fixed appliance because teeth are free of contact by the expander. And the best point for spike expander is that it is simply fabricated and removed. CONCLUSIONS: The design of spike expander is combining spike screws and an expansion screw, which can provide a good and easy treatment method for transverse maxillary deficiency. PMID- 26845097 TI - Pathologic Mandibular Fracture as First Sign of Multiple Myeloma. AB - Multiple myeloma (MM) is a neoplasia characterized by the proliferation of plasmacytoid cells, which produce abnormal immunoglobulins. It frequently creates local and systemic complications such as pathologic fractures and renal disease. This article reports the case of a 70-year-old man presenting a pathologic fracture of the right mandibular angle secondary to a plasmocytoma. He had a history of a previous pathologic fracture of the left mandibular angle 13 years before that was treated elsewhere, but no documentation was available. Investigation revealed the disease to be a MM and evolution led to renal failure and death. Differential diagnosis is necessary for this kind of pathologic presentation because MM presents a survival rate of 5.7% in 5 years and mandibular involvement happens in the advanced stage of the disease. PMID- 26845098 TI - Does Vitamin D3 Have an Impact on Clinical and Biochemical Parameters Related to Third Molar Surgery. AB - The purpose of this study was to evaluate the clinical effect on the biochemical inflammatory markers of a single oral high dose of cholecalciferol in vitamin D deficient patients undergoing the surgical removal of lower third molars.A randomized, split-mouth, single-blind study was conducted on 25 vitamin D deficient patients ranging between 18 and 40 years of age requiring lower third molars extraction and referred at the Oral Surgery Unit of the School of Dentistry of the University of Messina.All patients, with vitamin D3 blood levels ?30 ng/mL, underwent bilateral surgical removal. The first extraction (control group) being conducted with the administration of a placebo, the second one (test group) being conducted with the preliminary administration of 300,000 IU of cholecalciferol 4 days before the procedure.At each surgery, clinical indexes, such as pain, edema and any functional limitation have been recorded. Clinical and biochemical parameters were registered 4 days before, immediately after, 3 and 7 days after the surgical procedure. The data obtained were processed using paired t-test. The clinical outcome parameters showed a slight to moderate improvement between the control and the vitamin-D treatment group, with statistical significance being obtained regarding the edema at defined time points. Interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha values were significantly lower (P < 0.01) for the test group after the surgery. The increase of vitamin D serum levels showed an impact on the outcome of the third molar surgery, eliciting a reduced inflammatory response and leading to a more favorable clinical course. PMID- 26845099 TI - Management of a Rare Case of Invasive Fungal Sinusitis. PMID- 26845100 TI - Infratemporal Fossa Abscess of Dental Origin: A Rare, Severe, and Misdiagnosed Infection. PMID- 26845101 TI - HIV Testing and Service Delivery Among Black Females--61 Health Department Jurisdictions, United States, 2012-2014. AB - A primary goal of the national human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) Strategy is to reduce HIV-related health disparities (1). Among all HIV diagnoses among women in the United States in 2014, non-Hispanic black or African American (black) women accounted for an estimated 62% of diagnoses, despite constituting only 13% of the female population (2,3). Although HIV diagnoses continue to occur disproportionately among black women, HIV surveillance data indicate a 13.5% decrease in diagnoses from 2012 to 2014 (2,4). However, widespread HIV testing and early linkage to care are critical for persons with HIV to achieve viral suppression and improved health outcomes, and to reduce transmission of HIV to others (5). Analysis of CDC funded program data on HIV testing services provided to black females and submitted by 61 state and local health departments during 2012-2014 revealed that the number of new HIV diagnoses among black females decreased 17% from 2,177 in 2012 to 1,806 in 2014. Among black females with newly diagnosed HIV infection, the percentage who were linked to HIV medical care within 90 days of diagnosis increased 48.2%, from 33.8% in 2012 to 50.1% in 2014. However, in 2010 the National HIV/AIDS Strategy established a goal to link 85% of persons with newly diagnosed HIV infection to HIV medical care (1). Enhanced efforts to diagnose HIV infection among black females and link them to HIV medical care are critical to address HIV infections in the United States. PMID- 26845102 TI - Probing Chromatin-modifying Enzymes with Chemical Tools. AB - Chromatin is the universal template of genetic information in all eukaryotic organisms. Chemical modifications of the DNA-packaging histone proteins and the DNA bases are crucial signaling events in directing the use and readout of eukaryotic genomes. The enzymes that install and remove these chromatin modifications as well as the proteins that bind these marks govern information that goes beyond the sequence of DNA. Therefore, these so-called epigenetic regulators are intensively studied and represent promising drug targets in modern medicine. We summarize and discuss recent advances in the field of chemical biology that have provided chromatin research with sophisticated tools for investigating the composition, activity, and target sites of chromatin modifying enzymes and reader proteins. PMID- 26845103 TI - New targets for monitoring and therapy in Barth syndrome. AB - PURPOSE: Barth syndrome (BTHS), an X-linked disorder caused by defects in TAZ, is the only known single-gene disorder of cardiolipin remodeling. We hypothesized that through analysis of affected individuals, we would gain a better understanding of the range of clinical features and identify targets for monitoring and therapy. METHODS: We conducted a multidisciplinary investigation involving 42 patients with BTHS, including echocardiograms, muscle strength testing, functional exercise capacity testing, physical activity assessments, cardiolipin analysis, 3-methylglutaconic acid analysis, and review of genotype data. We analyzed data points to provide a quantitative spectrum of disease characteristics and to identify relationships among phenotype, genotype, and relevant metabolites. RESULTS: Echocardiography revealed considerable variability in cardiac features. By contrast, almost all patients had significantly reduced functional exercise capacity. Multivariate analysis revealed significant relationships between cardiolipin ratio and left ventricular mass and between cardiolipin ratio and functional exercise capacity. We additionally identified genotypes associated with a less severe metabolic and clinical profile. CONCLUSION: We defined previously unrecognized metabolite/phenotype/genotype relationships, established targets for therapeutic monitoring, and validated avenues for clinical assessment. In addition to providing insight into BTHS, these studies also provide insight into the myriad of multifactorial disorders that converge on the cardiolipin pathway.Genet Med 18 10, 1001-1010. PMID- 26845105 TI - Should states adopt newborn screening for early infantile Krabbe disease? AB - The published experience to date regarding implementing NBS for EIKD has been dramatically enhanced by the data presented in this issue by Orsini et al. Although much has been written about the potential harms to individuals with an abnormal NBS for EIKD who do not have EIKD, several commentators have also asked whether screening provides a benefit when it leads to early identification of the disorder. Orsini and colleagues' data suggest that the state-mandated, multimillion-dollar NBS program for EIKD in New York has failed to provide significant benefit to children with EIKD. Indeed, in addition to the potential harm to families receiving false-positive test results, NBS for EIKD appears to have resulted in a reduction in survival in individuals who have the disease. The data from the New York program suggest that NBS for EIKD should be abandoned, pending the development of improved screening or therapies shown to confer both survival and quality-of-life benefits over supportive care. The results of this experience suggest that research efforts should be focused on improving presymptomatic treatment outcomes in children identified by NBS prior to the redeployment of mandatory presymptomatic screening. PMID- 26845104 TI - Improving performance of multigene panels for genomic analysis of cancer predisposition. AB - PURPOSE: Screening multiple genes for inherited cancer predisposition expands opportunities for cancer prevention; however, reports of variants of uncertain significance (VUS) may limit clinical usefulness. We used an expert-driven approach, exploiting all available information, to evaluate multigene panels for inherited cancer predisposition in a clinical series that included multiple cancer types and complex family histories. METHODS: For 1,462 sequential patients referred for testing by BROCA or ColoSeq multigene panels, genomic DNA was sequenced and variants were interpreted by multiple experts using International Agency for Research on Cancer guidelines and incorporating evolutionary conservation, known and predicted variant consequences, and personal and family cancer history. Diagnostic yield was evaluated for various presenting conditions and family-history profiles. RESULTS: Of 1,462 patients, 12% carried damaging mutations in established cancer genes. Diagnostic yield varied by clinical presentation. Actionable results were identified for 13% of breast and colorectal cancer patients and for 4% of cancer-free subjects, based on their family histories of cancer. Incidental findings explaining cancer in neither the patient nor the family were present in 1.7% of subjects. Less than 1% of patients carried VUS in BRCA1 or BRCA2. For all genes combined, initial reports contained VUS for 10.5% of patients, which declined to 7.5% of patients after reclassification based on additional information. CONCLUSIONS: Individualized interpretation of gene panels is a complex medical activity. Interpretation by multiple experts in the context of personal and family histories maximizes actionable results and minimizes reports of VUS.Genet Med 18 10, 974-981. PMID- 26845107 TI - Interactions in Ternary Mixtures of MnO2, Al2O3, and Natural Organic Matter (NOM) and the Impact on MnO2 Oxidative Reactivity. AB - Our previous work reported that Al2O3 inhibited the oxidative reactivity of MnO2 through heteroaggregation between oxide particles and surface complexation of the dissolved Al ions with MnO2 (S. Taujale and H. Zhang, "Impact of interactions between metal oxides to oxidative reactivity of manganese dioxide" Environ. Sci. Technol. 2012, 46, 2764-2771). The aim of the current work was to investigate interactions in ternary mixtures of MnO2, Al2O3, and NOM and how the interactions affect MnO2 oxidative reactivity. For the effect of Al ions, we examined ternary mixtures of MnO2, Al ions, and NOM. Our results indicated that an increase in the amount of humic acids (HAs) increasingly inhibited Al adsorption by forming soluble Al-HA complexes. As a consequence, there was less inhibition on MnO2 reactivity than by the sum of two binary mixtures (MnO2+Al ions and MnO2+HA). Alginate or pyromellitic acid (PA)-two model NOM compounds-did not affect Al adsorption, but Al ions increased alginate/PA adsorption by MnO2. The latter effect led to more inhibition on MnO2 reactivity than the sum of the two binary mixtures. In ternary mixtures of MnO2, Al2O3, and NOM, NOM inhibited dissolution of Al2O3. Zeta potential measurements, sedimentation experiments, TEM images, and modified DLVO calculations all indicated that HAs of up to 4 mg-C/L increased heteroaggregation between Al2O3 and MnO2, whereas higher amounts of HAs completely inhibited heteroaggregation. The effect of alginate is similar to that of HAs, although not as significant, while PA had negligible effects on heteroaggregation. Different from the effects of Al ions and NOMs on MnO2 reactivity, the MnO2 reactivity in ternary mixtures of Al2O3, MnO2, and NOM was mostly enhanced. This suggests MnO2 reactivity was mainly affected through heteroaggregation in the ternary mixtures because of the limited availability of Al ions. PMID- 26845108 TI - The role of iron in the management of chemotherapy-induced anemia in cancer patients receiving erythropoiesis-stimulating agents. AB - BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are commonly used to treat chemotherapy-induced anemia (CIA). However, about half of patients do not benefit. OBJECTIVES: To evaluate the benefits and harms related to the use of iron as a supplement to ESA and iron alone compared with ESA alone in the management of CIA. SEARCH METHODS: We searched for relevant trials from the Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1 January 2016), MEDLINE (1950 to February 2016), and www.clinicaltrials.gov without using any language limits. SELECTION CRITERIA: All randomized controlled trials (RCTs) comparing 'iron plus ESA' or 'iron alone' versus 'ESA alone' in people with CIA were eligible for inclusion. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included eight RCTs (12 comparisons) comparing ESA plus iron versus ESA alone enrolling 2087 participants. We did not find any trial comparing iron alone versus ESAs alone in people with CIA. None of the included RCTs reported overall survival. There was a beneficial effect of iron supplementation to ESAs compared with ESAs alone on hematopoietic response (risk ratio (RR) 1.17, 95% confidence interval (CI) 1.09 to 1.26; P < 0.0001; 1712 participants; 11 comparisons; high-quality evidence). Assuming a baseline risk of 35% to 80% for hematopoietic response without iron supplementation, between seven and 16 patients should be treated to achieve hematopoietic response in one patient. In subgroup analyses, RCTs that used intravenous (IV) iron favored ESAs and iron (RR 1.20 (95% CI 1.10 to 1.31); P < 0.00001; 1321 participants; eight comparisons), whereas we found no evidence for a difference in hematopoietic response in RCTs using oral iron (RR 1.04 (95% CI 0.87 to 1.24); P = 0.68; 391 participants; three comparisons). There was no evidence for a difference between the subgroups of IV and oral iron (P = 0.16). There was no evidence for a difference between the subgroups of types of iron (P = 0.31) and types of ESAs (P = 0.16) for hematopoietic response.The iron supplementation to ESAs might be beneficial as fewer participants treated with iron supplementation required red blood cell (RBC) transfusions compared to the number of participants treated with ESAs alone (RR 0.74 (95% CI 0.60 to 0.92); P = 0.007; 1719 participants; 11 comparisons; moderate-quality evidence). Assuming a baseline risk of 7% to 40% for RBC transfusion without iron supplementation, between 10 and 57 patients should be treated to avoid RBC transfusion in one patient.We found no evidence for a difference in the median time to hematopoietic response with addition of iron to ESAs (hazard ratio (HR) 0.93 (95% CI 0.67 to 1.28); P = 0.65; 1042 participants; seven comparisons; low-quality evidence). In subgroup analyses, RCTs in which dextran (HR 0.95 (95% CI 0.36 to 2.52); P = 0.92; 340 participants; three comparisons), sucrose iron (HR 1.15 (95% CI 0.60 to 2.21); P = 0.67; 102 participants; one comparison) and sulfate iron (HR 1.24 (95% CI 0.99 to 1.56); P = 0.06; 55 participants; one comparison) were used showed no evidence for difference between iron supplementation versus ESAs alone compared with RCTs in which gluconate (HR 0.78 (95% CI 0.65 to 0.94); P = 0.01; 464 participants; two comparisons) was used for median time to hematopoietic response (P = 0.02). There was no evidence for a difference between the subgroups of route of iron administration (P = 0.13) and types of ESAs (P = 0.46) for median time to hematopoietic response.Our results indicated that there could be improvement in the hemoglobin (Hb) levels with addition of iron to ESAs (mean difference (MD) 0.48 (95% CI 0.10 to 0.86); P = 0.01; 827 participants; seven comparisons; low quality evidence). In RCTs in which IV iron was used there was evidence for a difference (MD 0.84 (95% CI 0.21 to 1.46); P = 0.009; 436 participants; four comparisons) compared with oral iron (MD 0.07 (95% CI -0.19 to 0.34); P = 0.59; 391 participants; three comparisons) for mean change in Hb level (P = 0.03). RCTs in which dextran (MD 1.55 (95% CI 0.62 to 2.47); P = 0.001; 102 participants; two comparisons) was used showed evidence for a difference with iron supplementation versus ESAs alone compared with RCTs in which gluconate (MD 0.54 (95% CI -0.15 to 1.22); P = 0.12; 334 participants; two comparisons) and sulfate iron (MD 0.07 (95% CI -0.19 to 0.34); P = 0.59; 391 participants; three comparisons) were used for mean change in Hb level (P = 0.007). RCTs in which epoetin was used showed evidence for a difference with iron supplementation versus ESAs alone (MD 0.77 (95% CI 0.25 to 1.29); P = 0.004; 337 participants; five comparisons) compared with darbepoetin use (MD 0.10 (95% CI -0.13 to 0.33); P = 0.38; 490 participants; two comparisons) for mean change in Hb level (P = 0.02).We found no evidence for a difference in quality of life with addition of iron to ESAs (standardized mean difference 0.01 (95% CI -0.10 to 0.12); P = 0.88; 1124 participants; three RCTs; high-quality evidence).We found no evidence for a difference in risk of grade III IV thromboembolic events (RR 0.95 (95% CI 0.54 to 1.65); P = 0.85; 783 participants; three RCTs; moderate-quality evidence). The incidence of treatment related mortality (TRM) was 0% (997 participants; four comparisons; high-quality evidence).Other common adverse events included vomiting, asthenia, and leukopenia, and were similar in both arms.Overall the risk of bias across outcomes was high to low. Since the included RCTs had shorter follow-up duration (up to 20 weeks), the long-term effects of iron supplementation are unknown. Our main reasons for downgrading the quality of evidence were inconsistency across the included studies and imprecision of results. AUTHORS' CONCLUSIONS: Our systematic review shows that addition of iron to ESAs offers superior hematopoietic response, reduces the risk of RBC transfusions, and improves Hb levels, and appears to be well tolerated. None of the included RCTs reported overall survival. We found no evidence for a difference in quality of life with iron supplementation. PMID- 26845106 TI - Effectiveness of whole-exome sequencing and costs of the traditional diagnostic trajectory in children with intellectual disability. AB - PURPOSE: This study investigated whole-exome sequencing (WES) yield in a subset of intellectually disabled patients referred to our clinical diagnostic center and calculated the total costs of these patients' diagnostic trajectory in order to evaluate early WES implementation. METHODS: We compared 17 patients' trio-WES yield with the retrospective costs of diagnostic procedures by comprehensively examining patient records and collecting resource use information for each patient, beginning with patient admittance and concluding with WES initiation. We calculated cost savings using scenario analyses to evaluate the costs replaced by WES when used as a first diagnostic tool. RESULTS: WES resulted in diagnostically useful outcomes in 29.4% of patients. The entire traditional diagnostic trajectory average cost was $16,409 per patient, substantially higher than the $3,972 trio-WES cost. WES resulted in average cost savings of $3,547 for genetic and metabolic investigations in diagnosed patients and $1,727 for genetic investigations in undiagnosed patients. CONCLUSION: The increased causal variant detection yield by WES and the relatively high costs of the entire traditional diagnostic trajectory suggest that early implementation of WES is a relevant and cost-efficient option in patient diagnostics. This information is crucial for centers considering implementation of WES and serves as input for future value based research into diagnostics.Genet Med 18 9, 949-956. PMID- 26845110 TI - Assessing the Neural Correlates of Task-unrelated Thoughts during Episodic Encoding and Their Association with Subsequent Memory in Young and Older Adults. AB - Recent evidence indicates that young adults frequently exhibit task-unrelated thoughts (TUTs) such as mind-wandering during episodic encoding tasks and that TUTs negatively impact subsequent memory. In the current study, we assessed age related differences in the frequency and neural correlates of TUTs during a source memory encoding task, as well as age-related differences in the relationship between the neural correlates of TUTs and subsequent source forgetting effects (i.e., source misses). We found no age-related differences in frequency of TUTs during fMRI scanning. Moreover, TUT frequency at encoding was positively correlated with source misses at retrieval across age groups. In both age groups, brain regions including bilateral middle/superior frontal gyri and precuneus were activated to a greater extent during encoding for subsequent source misses versus source hits and during TUTs versus on-task episodes. Overall, our results reveal that, during a source memory encoding task in an fMRI environment, young and older adults exhibit a similar frequency of TUTs and that experiencing TUTs at encoding is associated with decreased retrieval performance. In addition, in both age groups, experiencing TUTs at encoding is associated with increased activation in some of the same regions that exhibit subsequent source forgetting effects. PMID- 26845111 TI - Energetic analysis and experiments of earthworm-like locomotion with compliant surfaces. AB - The energy consumption of worm robots is composed of three parts: heat losses in the motors, internal friction losses of the worm device and mechanical energy locomotion requirements which we refer to as the cost of transport (COT). The COT, which is the main focus of this paper, is composed of work against two types of external factors: (i) the resisting forces, such as weight, tether force, or fluid drag for robots navigating inside wet environments and (ii) sliding friction forces that may result from sliding either forward or backward. In a previous work, we determined the mechanical energy requirement of worm robot locomotion over compliant surfaces, independently of the efficiency of the worm device. Analytical results were obtained by summing up the external work done on the robot and alternatively, by integrating the actuator forces over the actuator motions. In this paper, we present experimental results for an earthworm robot fitted with compliant contacts and these are post-processed to estimate the energy expenditure of the device. The results show that due to compliance, the COT of our device is increased by up to four-fold compared to theoretical predictions for rigid-contact worm-like locomotion. PMID- 26845109 TI - Decisions Made with Less Evidence Involve Higher Levels of Corticosubthalamic Nucleus Theta Band Synchrony. AB - The switch between automatic action selection and more controlled forms of decision-making is a dynamic process thought to involve both cortical and subcortical structures. During sensory conflict, medial pFC oscillations in the theta band (<8 Hz) drive those of the subthalamic nucleus (STN), and this is thought to increase the threshold of evidence needed for one competing response to be selected over another. Here, we were interested in testing whether STN activity is also altered by the rate at which evidence is presented during a congruent dot motion task absent of any explicit sensory conflict. By having a series of randomly moving dots gradually transform to congruent motion at three different rates (slow, medium, fast), we were able to show that a slower rate increased the time it took participants to make a response but did not alter the total amount of evidence that was integrated before the response. Notably, this resulted in a decision being made with a lower amount of instantaneous evidence during the slow and medium trials. Consistent with the idea that medial pFC-STN activity is involved in executing cognitive control, the higher levels of ambiguity during these trials were associated with increased theta band synchrony between the cortex and the STN, with the cortical oscillations Granger-causal to those of the STN. These results further confirm the involvement of the STN in decision-making and suggest that the disruption of this network may underlie some of the unwanted cognitive deficits associated with STN deep brain stimulation. PMID- 26845112 TI - Voriconazole Therapeutic Drug Monitoring Practices in Intensive Care. AB - BACKGROUND: Routine therapeutic drug monitoring of voriconazole seems to be beneficial. This study investigated the therapeutic drug monitoring practices in intensive care to derive possible recommendations for improvement. METHODS: A retrospective chart review was performed for patients aged >=18 years who started treatment with voriconazole, which lasted for at least 3 days while being admitted to an intensive care unit to assess possible differences between the patients with and without voriconazole trough concentrations measured. RESULTS: In 64 (76%) of the 84 patients, voriconazole trough concentrations were measured. The groups differed significantly with respect to the duration of voriconazole treatment and intensive care unit admission. Time of sampling was very early and therefore inappropriate for 49% of the first measured voriconazole trough concentrations and in 48% of the subsequent measured concentrations. Of the 349 trough concentrations measured, 129 (37%) were outside the therapeutic window. In 11% of these cases, no recommendation was provided without identifiable reason. In addition, 27% of recommended dose adjustments were not implemented, probably because the advice was not suited for the specific clinical situation. CONCLUSIONS: The performance of voriconazole therapeutic drug monitoring can still be improved although voriconazole concentrations were monitored in most patients. A multidisciplinary approach-for instance by means of antifungal stewardship-will probably be able to overcome problems encountered such as timing of sampling, incompleteness of data in clinical context, and lack of implementation of recommendations. PMID- 26845113 TI - Membrane Desalination: Where Are We, and What Can We Learn from Fundamentals? AB - Although thermal desalination technology provides potable water in arid regions (e.g., Israel and the Gulf), its relatively high cost has limited application to less arid regions with large populations (e.g., California). Energy-intensive distillation is currently being replaced with less costly pressure- and electrically driven membrane-based processes. Reverse osmosis (RO) is a preferred membrane technology owing to process and pre- and posttreatment improvements that have significantly reduced energy requirements and cost. Further technical advances will require a deeper understanding of the fundamental science underlying RO. This includes determining the mechanism for water selectivity; elucidating the behavior of molecular water near polar and apolar surfaces, as well as the advantages and limitations of hydrophobic versus hydrophilic pores; learning the rules of selective water transport from nature; and designing synthetic analogs for selective water transport. Molecular dynamics simulations supporting experiments will play an important role in advancing these efforts. Finally, future improvements in RO are limited by inherent technical mass transfer limitations. PMID- 26845114 TI - Strategies to Improve Outcomes of Patients with EGRF-Mutant Non-Small Cell Lung Cancer: Review of the Literature. AB - Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) monotherapy has been regarded as the standard first-line treatment of advanced non-small cell lung cancer (NSCLC) in patients with sensitive epidermal growth factor receptor gene (EGFR) mutations. Acquired resistance is inevitable, however, which presents a challenge in the management of patients with such mutations. Here, we summarize the clinical evidence on treatment strategies for both EGFR TKI-naive and acquired EGFR TKI-resistant NSCLC. We reviewed the published literature and abstracts of oral and poster presentations from international conferences addressing treatment strategies that are in use or in clinical development to improve the survival of patients who are EGFR TKI naive and EGFR TKI resistant. Various strategies have been explored to manage EGFR TKI resistance with the aim of prolonging the survival of patients with EGFR-mutant NSCLC. Combination strategies in the first-line treatment have been studied most to improve the benefit from EGFR TKI monotherapy and delay the occurrence of resistance. After failure of EGFR TKI monotherapy, continuation of EGFR TKI therapy combined with chemotherapy, immunotherapy, or targeted agents has been used to overcome the development of resistance. In addition, novel compounds designed to act on specific targets associated with EGFR TKI resistance have been in continued clinical development. Treatment regimens that are superior to EGFR TKI monotherapy in the first-line or to overcome acquired EGFR TKI resistance in patients with NSCLC and EGFR mutations still need to be developed. Results of ongoing studies will provide more insight into effective treatment strategies for patients with EGFR mutations. PMID- 26845115 TI - Screening with Low-Dose Computed Tomography Does Not Improve Survival of Small Cell Lung Cancer. AB - INTRODUCTION: Small cell lung cancer (SCLC) constitutes a distinct component of symptomatic or advanced-stage lung cancers in clinical practice and in lung cancer screening trials. The purpose of this study was to describe the outcome of SCLC in lung cancer screening trials and compare the frequency of SCLC in our cohort with that in the major lung cancer screening trials. METHODS: Subjects with a diagnosis of SCLC were selected from two lung cancer screening trials by low-dose computed tomography (LDCT), and their demographic characteristics, clinical parameters, tumor stage at diagnosis, therapy, and survival times were recorded. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Ten cases of SCLC were reported in 45,141 person-years (22 in 100,000 person years), representing the 6% of all lung cancer cases. Cumulative tobacco consumption was 82 pack-years compared with 39 and 46 pack-years for the overall study population and subjects with non-SCLC, respectively. Most of the neoplasms were in an advanced stage (seven in stage IV and one each in stages IIIb, IIIa, and Ia). Two subjects were treated with lobectomy for curative purposes and died of diffuse metastasis within 2 years of diagnosis. The median overall survival time in the LDCT arms was 20.6 months, with no survivors remaining at 3 years. CONCLUSIONS: Subjects in whom SCLC develops are a subgroup of smokers with extremely high cumulative tobacco consumption. Consequently, the frequency of SCLC in our population was lower than in other screening populations, with higher cumulative tobacco consumption. Screening for lung cancer by LDCT does not improve survival of SCLC, with no survivors remaining at 3 years after diagnosis. PMID- 26845116 TI - Multiplex Diagnosis of Oncogenic Fusion and MET Exon Skipping by Molecular Counting Using Formalin-Fixed Paraffin Embedded Lung Adenocarcinoma Tissues. AB - INTRODUCTION: Fusions of the anaplastic lymphoma receptor tyrosine kinase gene (ALK), ret proto-oncogene (RET), ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS1), B-Raf proto-oncogene, serine/threonine kinase gene (BRAF), and neuregulin 1 gene (NRG1) and intronic MMNG HOS Transforming gene (MET) mutations are druggable oncogene alterations in lung adenocarcinoma that cause expression of aberrant transcripts. Because these aberrant transcripts are both infrequent (incidence <5%) and mutually exclusive, multiplex assays are required to detect them in tumor samples. METHODS: Aberrant transcripts of the six aforementioned oncogenes (36 transcripts in total) were examined in a molecular counting (MC) assay, which counts RNA molecules by simultaneous hybridization of several probes. Forty-one samples of surgically resected lung adenocarcinoma tissue found to express one of these aberrant oncogenic transcripts upon whole transcriptome sequencing (test cohort: n = 22) or reverse transcription polymerase chain reaction (validation cohort: n = 19) analyses were subjected to MC, after which biopsies were performed on tumor tissue samples. RESULTS: Threshold values for the diagnosis of each of the 36 transcripts were determined in frozen and formalin-fixed paraffin-embedded samples from the test cohort. On the basis of these threshold values, the MC assay diagnosed expression of oncogenic transcripts in the validation cohort samples with 100% accuracy. The assay also accurately detected oncogenic fusions in bronchial lavage fluid and transbronchial biopsy samples. CONCLUSIONS: The MC assay allows multiplex detection of oncogenic fusion and exon-skipped transcripts in tumor samples, including in formalin-fixed paraffin-embedded samples obtained in the clinic. PMID- 26845117 TI - Assessing the Impact of Postoperative Radiation Therapy for Completely Resected Limited-Stage Small Cell Lung Cancer Using the National Cancer Database. AB - INTRODUCTION: Surgical resection is being increasingly used for early-stage small cell lung cancer (SCLC). However, there are sparse data regarding the role of adjuvant therapies, particularly postoperative radiation therapy (PORT). We investigated the impact of PORT on survival after complete surgical resection for SCLC using the National Cancer Database. METHODS: There were 3017 patients diagnosed with nonmetastatic SCLC between 1998 and 2011 who underwent R0 sublobar resection, lobectomy, or pneumonectomy. Patients were stratified by the use of PORT, and only those who received a minimum dose of 45 Gy were included. The overall survival (OS) of patients based on PORT use were analyzed by Kaplan-Meier analysis and compared using the log-rank test. Multivariate Cox regression analysis was used to identify factors associated with survival. RESULTS: For the entire study population, the 5-year OS was significantly poorer with the addition of PORT (33.9% versus 40.6%; p = 0.005). When analyzed by subgroup, patients with pN0 stage had significantly decreased OS with PORT (39.3% versus 46.3%; p = 0.07) and patients with pN2 stage had significantly improved OS with PORT (29.0% versus 18.6%; p < 0.001). No differences in OS were observed in patients with pN1 stage. On multivariate analysis, the hazard ratio for PORT in pN0 disease was 1.36 (95% confidence interval, 1.09-1.70; p < 0.001) and the hazard ratio for PORT in pN2 disease was 0.60 (95% confidence interval, 0.45-0.80; p < 0.001). CONCLUSION: The use of PORT was associated with a deleterious effect on OS in patients with pN0 disease but significantly improved OS in patients with pN2 disease. PMID- 26845118 TI - Contemporary Analysis of Prognostic Factors in Patients with Unresectable Malignant Pleural Mesothelioma. AB - INTRODUCTION: Previous prognostic scoring systems for malignant pleural mesothelioma (MPM) included patients managed surgically and predated the use of pemetrexed. We analyzed prognostic factors in a contemporary cohort of patients with unresectable MPM who received pemetrexed-based chemotherapy. METHODS: This single-institution analysis included patients with MPM who were managed nonsurgically from 2000 to 2013. Variables correlated with overall survival (OS) included sex, performance status (PS), asbestos exposure, tumor laterality, histology, clinical stage, initial positron emission tomography maximum standardized uptake value, hemoglobin level, platelet count, lymphocyte count, white cell and neutrophil counts, treatment type, and clinical benefit from treatment. OS was analyzed by the Kaplan-Meier method, and significance (p < 0.05) of prognostic factors was analyzed by the log-rank test and Cox regression. RESULTS: A total of 191 patients met the study criteria: median age 71 years (range 46-90), 147 men (77%), 128 epithelioid tumors (67%), and 157 cases of stage III or IV MPM (82%). Median OS for all patients was 13.4 months. According to a univariate analysis, histology (p < 0.001), platelet count (< or = 450,000 versus >450,000, p < 0.001), initial PS (0-1 versus > or = 2), maximum standardized uptake value (< or = 8.1 versus >8.1, p = 0.037), and lymphocyte counts (p = 0.019) were associated with OS. According to a multivariable analysis, only histology, platelet count, and PS were independent prognostic factors. Epithelioid histology, PS, and elevated lymphocyte count at diagnosis were significantly associated with clinical benefit from first-line chemotherapy. CONCLUSIONS: Our results confirm the significance of elements of the Cancer and Leukemia Group B and European Organisation for Research and Treatment of Cancer prognostic scoring systems, identify factors associated with clinical benefit from chemotherapy, and emphasize the impact of histology and clinical benefit of chemotherapy on outcomes. PMID- 26845120 TI - Large Bronchopleural Fistula After Surgical Resection: Secret to Success. PMID- 26845119 TI - Alectinib Dose Escalation Reinduces Central Nervous System Responses in Patients with Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer Relapsing on Standard Dose Alectinib. AB - The central nervous system (CNS) is an important and increasingly recognized site of treatment failure in anaplastic lymphoma kinase (ALK)-positive, non-small cell lung cancer (NSCLC) patients receiving ALK inhibitors. In this report, we describe two ALK-positive patients who experienced initial improvements in CNS metastases on standard dose alectinib (600 mg twice daily), but who subsequently experienced recurrences with symptomatic leptomeningeal metastases. Both patients were dose-escalated to alectinib 900 mg twice daily, resulting in repeat clinical and radiographic responses. Our results suggest that dose intensification of alectinib may be necessary to overcome incomplete ALK inhibition in the CNS and prolong the durability of responses in patients with CNS metastases, particularly those with leptomeningeal carcinomatosis. PMID- 26845121 TI - Acquired EGFR Mutation as the Potential Resistance Driver to Crizotinib in a MET Mutated Tumor. PMID- 26845122 TI - Genetic Basis of Mesothelioma--More Than Asbestos Exposure. PMID- 26845123 TI - Neuronal Acetylcholine Nicotinic Receptors as New Targets for Lung Cancer Treatment. AB - Lung cancer is the leading cause of cancer-related deaths worldwide. Smoking accounts for approximately 70% of the cases of non- small cell lung cancer (NSCLC) and 90% of the cases of small-cell lung cancer (SCLC), although some patients develop lung cancer without a history of smoking. Nicotine is the most active addictive component of tobacco smoke. It does not initiate tumorigenesis in humans and rodents, but it alters the pathophysiology of lung cells by inducing the secretion of growth factors, neurotransmitters and cytokines, and promotes tumour growth and metastases by inducing cell cycle progression, migration, invasion, angiogenesis and the evasion of apoptosis. Most of these effects are a result of nicotine binding and activation of cell-surface neuronal nicotinic acetylcholine receptors (nAChRs) and downstream intracellular signalling cascades, and many are blocked by nAChR subtype-selective antagonists. Recent genome-wide association studies have revealed single nucleotide polymorphisms of nAChR subunits that influence nicotine dependence and lung cancer. This review describes the molecular basis of nAChR structural and functional diversity in normal and cancer lung cells, and the genetic alterations facilitating smoking-induced lung cancers. It also summarises current knowledge concerning the intracellular pathways activated by nicotine and other compounds present in tobacco smoke. PMID- 26845124 TI - Biomimetic Approach to Stimulate Osteogenesis on Titanium Implant Surfaces Using Fibronectin Derived Oligopeptide. AB - Our previous studies demonstrated that a recombinant fibronectin (FN)-derived oligopeptide that we named F20 stimulated osteoblast adhesion, proliferation, and differentiation in vitro and in vivo. In the present study, we used a synthetic oligopeptide and investigated the osteogenic potential of F20 coating on titanium discs, to stimulate superior osseointegration for dental implant surface modification. Surface characteristic analysis of titanium was performed by confocal laser scanning microscopy (CLSM) observation. Synthetic F20 was coated onto the machined or SLA titanium discs by an adsorption procedure. ST2 cells were seeded on the titanium discs. We evaluated cell adhesion with SEM and CLSM observation, cell proliferation with picogreen assay, and osteoblast differentiation with real-time PCR, ALP activity assay, immunoblot assay and ALP staining. FITC-labeled F20 coating on the discs was detected by fluorescence, showing good F20 adsorption and different coating patterns according to the surface roughness. In the SEM and CLSM observations, cells were well attached on the machined surface and greater stress fiber formation was seen on discs coated with F20 than on other discs. F20 stimulated cellular proliferation, as well as osteoblast differentiation through the extracellular signalregulated kinase (Erk) signaling pathway. These cellular responses to F20 were slightly better on the machined titanium surface than the SLA surface. These results suggest that F20 promotes osteogenesis through the Erk pathway and is a suitable biomolecule for surface modification of dental implants for improved osseointegration. PMID- 26845125 TI - Aptamers to Hemagglutinin: A Novel Tool for Influenza Virus Recognition and Neutralization. AB - Influenza virus can cause epidemics and pandemics of flu. A highly variable virus genome is responsible for the existence of different viral strains and acquired resistance to antiviral drugs. Today, only one class of therapeutics, neuraminidase inhibitors, is efficient and proved for influenza prophylaxis and treatment; whereas M2 protein inhibitors became inefficient due to evolving drug resistance. Therefore, there is an urgent need for the development of novel therapeutics. Aptamers are promising molecular recognition elements of high specificity and low toxicity, but only a few of them are under development as therapeutics. After selection of primary aptamers, there are sophisticated steps of further adjustments to the target and meeting requirements for therapeutics. In the last decade, dozens of DNA and RNA aptamers to various influenza types have been selected, but no comparative analyses have been performed yet. Most of aptamers were selected to hemagglutinin, a viral surface protein, which supports the first stages of virus invasion into the host cell. In the review, all available data on aptamers to hemagglutinin are analyzed. Aptamer specificity and affinity are discussed, as well as examples of aptamer applications for virus detection and virus infection inhibition. In summary, aptamers can be selected for hemagglutinin recognition, aptamers to hemagglutinin can recognize viruses with different specificity, and some aptamers can neutralize virus in vitro, ex vivo and in vivo. Special sections of the review are dedicated to the original structural analyses. Some structural similarities among different aptamers have been revealed suggesting involvement into the target recognition. PMID- 26845127 TI - Dendritic Cells in Colorectal Cancer and a Potential for their Use in Therapeutic Approaches. AB - Multiple pathogenic mechanisms contribute to the development of colorectal cancer. This tumor is characterized by high chemoresistance and low immunogenicity due to the effective mechanisms of immunosuppression. Dendritic cells (DCs) play a key role in recognition of tumor antigens and induction of T cell-primed anticancer response. However, in cancer microenvironment, the function of tumor-infiltrating DCs becomes impaired and switched from the immunostimulation to the immunosuppression. Colorectal cancer cells express anti inflammatory cytokines such as IL-10 and TGF-beta that could affect DC phenotype and support tumor escape from the immune surveillance. As a result, tumor associated DCs display numerous defects in antigen-presenting capacity and have an altered pattern of expression of immune costimulatory molecules towards the immunoregulatory phenotype. Indeed, understanding of mechanisms, such as how tumor could impair activity of DCs, would help in the development of new DC-based vaccines against colorectal cancer. PMID- 26845126 TI - Pharmacotherpy and Alzheimer's Disease: The M-Drugs (Melatonin, Minocycline, Modafinil, and Memantine) Approach. AB - Despite advances in understanding the pathophysiology of Alzheimer's disease (AD), its therapy remains largely symptomatic and supportive. Acetylcholinesterase inhibitors - the first-line drugs used today do not prevent and treat AD. So far, over 90 Phase 3 trials of AD have been unsuccessful with 99.0% failure rate. There is, therefore, an urgent need to find effective new therapies for AD. Owing to the multifactorial nature of AD pathogenesis, polypharmacy with drugs that target heterogeneous pathophysiological pathways, needs to be considered. Fortunately, several drugs used currently in clinical use as monotherapies can be exploited in AD. This article, therefore, presents a novel pharmacological treatment paradigm and recommends the use of valuable diseasemodifying approved drugs, viz. melatonin, minocycline, modafinil, and memantine (the "M" Drugs). Melatonin - a neuroprotector is an antioxidant and anti-inflammatory. Minocycline is also neuroprotective, it reduces neuroinflammation and CNS pathology and prevents cell death. Sleep deprivation leads to decreased hippocampal neurogenesis, increased amyloid beta generation, and causes memory dysfunction. Modafinil - a wake-promoting agent is approved for use in narcolepsy and obstructive sleep apnea. It improves global mental status, hippocampal neurogenesis, attention, and cognition. Memantine is an uncompetitive N-methyl-d-aspartic acid receptor antagonist and is approved for the management of moderate-to-severe AD. The paramount possible beneficial effects of the M drugs may include significant memory and cognitive enhancement in aging, mild cognitive impairment, and AD. The M drugs-centric pharmacotherapy strategy is comprehensive and pragmatic and is meant to combat multiple pathological targets and ameliorate cognitive dysfunction/AD. PMID- 26845128 TI - Scaffolds for Bone Regeneration: State of the Art. AB - Nowadays, millions of people worldwide are affected by problems of bones and articulations. These conditions represent about a half of the chronic diseases developed in individuals over 50 years, leading to problems of prolonged pain and physical inability, which usually require surgery, where bone grafts or implants are used. Nonetheless, despite the success of these therapeutic solutions, some drawbacks have been pointed out, related with the risk of developing infections after implant application within the body. Moreover, grafts are associated to pain, infection, tissue death at the donor site and immunological rejection. To overcome these limitations, tissue engineering has an important role that constitutes a promising area for repair and rebuild bone lesions, through the development of three-dimensional (3D) porous matrices, commonly known as scaffolds. Associated with these structures are mesenchymal stem cells and growth factors, which lead to the formation of new bone by stimulating the natural regeneration ability of the patient's tissue. In this review, we address the most important methodologies and concepts regarding tissue engineering for the replacement of bone tissue. The concept of scaffold, and examples of different types of scaffolds and their respective production methods are presented. In vitro and in vivo techniques to evaluate the suitability of scaffolds for human use are discussed. In addition, some of the most recent studies regarding the application of scaffolds for bone tissue engineering are described. PMID- 26845129 TI - The Heat Stress Response and Diabetes: More Room for Mitochondrial Implication. AB - Heat preconditioning is a rapid cellular adaptive mechanism shared by many cells/ organs / organisms that results in synthesis and accumulation of heat shock proteins (HSPs), which are responsible for increased tolerance and survival of animals during and after heat stress (HS). HSPs function as molecular chaperones by restoring cellular homeostasis and promoting cell survival, and their major functions include protection of cells from injury by preventing protein damage and aggregation. Abundant evidence points to the ability of one kind of stress caused by external factors that induce primary adaptations in the organism to provide protection against additional stress of the same or another type, a phenomenon known as cross-tolerance. Diabetes mellitus (DM) is one of the diseases which have been associated with increased tissue sensitivity and vulnerability due to incorrect protein folding. Thus, HSPs may play an important role in minimizing the protein damage that can occur under the stressful conditions created by the disease. By increasing HSP production, heat preconditioning may be a promising therapy for patients with lifestylerelated diseases such as hypercholesterolemia, hypertension, DM and obesity. Also, pancreatic beta-cells exposed to acute HS activate defence mechanisms which include HSP synthesis and are less sensitive to the effects of cytotoxic agents such as NO, oxygen radicals and beta-cytotoxic diabetogenic agents, such as streptozotocin (STZ). Mitochondrial dysfunction and mitochondria-specific cell stress are associated and can even be a primary abnormality caused by DMinduced hyperglycaemia and oxidative stress. There are an increasing number of genetic and/or pharmacological modulations of HSPs that have revealed the connection between HSPs, mitochondria and diabetes. HSPs may affect mitochondrial function in multiple ways, but the influence on skeletal muscle and adipose tissue, as well as on the pancreas, has attracted most interest as a key element in the development of novel pharmacological approaches to treating DM and associated metabolic conditions. PMID- 26845130 TI - Synthesis of New Benzimidazole and Benzothiazole Disulfide Metal Complexes as G quadruplex Binding Ligands. AB - Compounds that can bind and stabilize non-canonical DNA structures are named quadruplex and are of interest in anticancer drug design due to their selective inhibitions of telomerase and consequent effects on cell proliferation. In this study, we report novel Co/Cu [II] complex compounds as G-quadruplex DNA binding ligands. The results from the preliminary assay indicated that the introduction of a positively charged 6-membered tail to the aromatic terminal group of benzimidazole significantly enhanced the binding affinity with the quadruplex and exhibited anti-telomerase activity. These derivatives showed significant selectivities for the telomeric quadruplex over duplex nucleic acids. The stabilization of non-canonical forms estimated with the FRET DNA technology using different sequences, such as F21T, c-kit1 and c-kit2, in cancer cell lines were assessed. Three members of this family showed to be very selective in stabilizing one particular G-quadruplex. PMID- 26845131 TI - Synthesis of Arylamino-1,3,5-triazines Functionalized with Alkylatin 2 chloroethylamine Fragments and Studies of their Cytotoxicity on the Breast Cancer MCF-7 Cell Line. AB - Dual action alkyl(aryl)amino-1,3,5-triazines functionalized with nitrogen mustards were obtained by treating 2-alkyl(aryl) amino-4-chloro-6-methoxy-1,3,5 triazines with amines or amino acid methyl esters, followed by reactions with 1,4 diazabicyclo[2.2.2]octane (DABCO) and rearrangement with an opening diazabicyclic fragment, leading to the formation of 2-chloroethylamino moiety. In vitro antitumor activity was tested in the standard human breast cancer MCF-7 and MDA MB-231cell lines using flow cytometry, based on the detection of apoptosis through qualitative analysis of morphological changes, DNA fragmentation, DNA loss and membrane changes. For all the compounds studied, induced apoptosis was substantially stronger than necrosis at concentrations of both 5 MUM and 50 MUM, and in some cases there was no increase in necrotic cell death for the estrogen dependent MCF-7 cell line. The most active compounds were derivatives of triazine substituted with phenylamine (IC50 = 12.30 MUM) and/or p-tolylamine fragments (IC50 = 7.40 MUM). PMID- 26845132 TI - Docking Studies of Glutamine Valproic Acid Derivative (S)-5- amino-2-(heptan-4 ylamino)-5-oxopentanoic Acid (Gln-VPA) on HDAC8 with Biological Evaluation in HeLa Cells. AB - In this contribution, we focused on evaluating a novel compound developed by our group. This molecule, derived from glutamine (Gln) and valproic acid (VPA), denominated (S)- 5-amino-2-(heptan-4-ylamino)-5-oxopentanoic acid (Gln-VPA), was submitted to docking studies on histone deacetylase 8 (HDAC8) to explore its non bonded interactions. The theoretical results were validated in HeLa cells as a cancer cell model and in human dermal fibroblasts as a normal cell model. The effects of Gln-VPA on HeLa and normal fibroblasts in terms of cell survival and the ability to inhibit HDAC activity in nude nuclear proteins and in nuclear proteins of whole cells treated for 24 h were analyzed. The HeLa cell cycle was analyzed after 24 and 48 h of treatment with Gln-VPA. The docking studies show that Gln-VPA can reach the catalytic site of HDAC8. Gln-VPA was organically synthesized with a purity greater than 97%, and its structure was validated using mass spectrometry, nuclear magnetic resonance and infrared spectroscopy. Gln-VPA showed a similar effect to VPA as an HDAC inhibitor but with less toxicity to fibroblasts. Although Gln-VPA was less efficient than VPA in reducing the survival of HeLa cells, it could be studied for use as a cancer cell sensitizer. PMID- 26845133 TI - Naphthoflavones as Antiproliferative Agents: Design, Synthesis and Biological Evaluation. AB - The present study involves the design and synthesis of naphthoflavones as antiproliferative agents. The strategy presents naphthoflavones as hybrids of naphthyl based chalcones and flavones. A panel of human cancer cell lines were employed for the cytotoxicity studies. DK-13 exhibited significant cytoxicity against MiaPaCa-2 cell lines with IC50 value of 1.93 MUM and 5.63 MUM against MCF 7 cell lines. The compound DK-13 was found to induce apoptosis evidenced through phase contrast microscopy, DAPI staining, and mitochondrial membrane potential loss. The cell phase distribution studies indicated an increase from 11.26 % (control sample) to 55.19 % (sample treated with 20 MUM compound DK-13) in the apoptotic population. PMID- 26845134 TI - Juglone Exerts Cytotoxic, Anti-proliferative and Anti-invasive Effects on Glioblastoma Multiforme in a Cell Culture Model. AB - In this study we evaluated the impact of juglone on rat glioma C6 cell culture viability, proliferation and invasiveness in vitro. Juglone induced C6 cell death with EC50 concentrations equal to 10.4 +/- 1.6 uM after 24h incubation. At relatively low concentrations juglone significantly decreased cell proliferation, reduced spheroid invasiveness and suppressed "wound" healing. In addition, generation of intracellular reactive oxygen and nitrogen species (RS) was detected in cells treated with juglone. Noteworthy, juglone was relatively stable in cell culture medium and levels of H2O2 generated from juglone due to its probable reaction with medium components were not sufficient to affect the viability of glioma cells. Moreover, addition of catalase to the cell medium did not reduce the cytotoxicity of juglone. Therefore, we propose that cell death may be induced through the action of RS other than H2O2, However the direct effect of juglone on the cellular targets could not be excluded either. In conclusion, juglone exerted cytotoxic, anti-proliferative and anti-invasive effects on C6 rat glioma cells in vitro. PMID- 26845135 TI - Peroxisome Proliferator-Activated Receptors and their Ligands in Cancer Drug- Resistance: Opportunity or Challenge. AB - Development of resistance in cancer cells results in a high failure rate in cancer chemotherapy in the clinic. Therefore, investigating the mechanisms by which cancer cells acquire the capability to avoid cell death upon exposure to antineoplastic agents is of great significance in cancer research. In this review article, we will provide an overview of the mechanisms and molecular machinery of drug resistance in cancer cells which include but may not be limited to altered membrane transport and drug metabolizing enzymes, genetic response, enhanced DNA repair and alternation in the target molecules. A special focus will be on describing the strategies and the rationale for exploitation of peroxisome proliferator-activated receptors for overcoming the observed resistance in cancer cells. PMID- 26845136 TI - 8-bromo-7-methoxychrysin Reversed M2 Polarization of Tumor-associated Macrophages Induced by Liver Cancer Stem-like Cells. AB - BACKGROUND: Hepatocellular carcinoma (HCC) is related to chronic liver inflammation. M2 polarization of tumor-associated macrophages (TAMs) in the tumor microenvironment promotes liver cancer stem-like cell (LCSLC) self-renewal capability and carcinogenicity. Therefore, reversing M2 polarization of TAMs could be an effective approach to cure HCC. OBJECTIVE: To evaluate whether 8 bromo-7-methoxychrysin (BrMC) has an effect on M2 polarization of TAMs. METHOD: LCSLC and conditional medium were obtained by sphere forming assay. Identification of LCSLC were analyzed by sphere forming, wound-healing and invasion assay. TAM and effects of BrMC on it were validated by immunofluorescence staining, ELISA and griess assay. Expressions of cancer stem cell and macrophage marker were analyzed by western blotting. RESULTS: Our results showed that BrMC significantly suppressed the expression of the M2 macrophage marker CD163. Furthermore, BrMC influenced the secretion profile of cytokines of TAMs. Mechanistically, BrMC reversed M2 polarization of TAMs due to inhibition of NF-kappaB activation. CONCLUSION: BrMC may be a potentially novel flavonoid agent that can be applied for disrupting the interaction of LCSLCs and TAMs. PMID- 26845138 TI - Synthesis of Combretastatin A-4 Analogs and their Biological Activities. AB - Combretastatin A-4 (CA-4) is a natural product, which consists of two phenyl rings, linked by an ethylene bridge. CA-4, inhibitor of polymerization of tubulin to microtubules, possesses a strong antitumor and anti-vascular properties both in vitro and in vivo. Previous studies showed that disodium phosphate salt of CA 4, a water-soluble prodrug is well tolerated at therapeutically useful doses. However, it should be noted that the cis-configuration of the double bond and the 3,4,5-trimethoxy group on ring A is necessary for the biological activity of CA 4. Structure of CA-4 renders the compound readily susceptible to isomerization, which reduces the potency and bioavailability. To circumvent this problem, a lot of scientists in the world synthesized a series of cis-restricted CA-4 analogs, where the double bond has been replaced by introduction of non-heterocyclic groups or heterocyclic groups like beta -lactam and oxadiazole. This paper reviews the most important approaches in analogs of combretastatin synthesis and presents structure-reactivity relationships for these compounds. PMID- 26845137 TI - Fibroblast Growth Factor Receptor (FGFR): A New Target for Non-small Cell Lung Cancer Therapy. AB - Lung cancer is still the leading cause of cancer related death worldwide. Fibroblast growth factor receptor (FGFR) is a tirosine-kinase receptor that is seen to be amplified or mutated in non-small cell lung cancer (NSCLC) and it plays a crucial role in tumour development and maintenance. The authors analyzed the state of the art of FGFR by reviewing the current literature. Fibroblast growth factor (FGF)-FGFR pathway and their aberrations are described, with the evaluation of their possible prognostic role in NSCLC and in particular in squamous cell carcinomas, in which FGFR is more often amplified. New therapeutic agents targeting FGFR signaling have been developed and are now in clinical evaluation. Dysregulation of FGF signaling in tumour cells is related to FGFR gene amplification or mutation, although it is still uncertain which of these aberrations represents a real predictor of response to specific inhibitors. However, recent evidence has questioned whether FGFR is a real target in squamous cell histology. The effectiveness of FGFR inhibitors is also still unclear since there are no clinical data on selected patients. Moreover, the management of specific side effects related to inhibition of the physiological role of FGF should be more thorough. PMID- 26845139 TI - A Human Factors Engineering Study of the Medication Delivery Process during an Anesthetic: Self-filled Syringes versus Prefilled Syringes. AB - BACKGROUND: Prefilled syringes (PFS) have been recommended by the Anesthesia Patient Safety Foundation. However, aspects in PFS systems compared with self filled syringes (SFS) systems have never been explored. The aim of this study is to compare system vulnerabilities (SVs) in the two systems and understand the impact of PFS on medication safety and efficiency in the context of anesthesiology medication delivery in operating rooms. METHODS: This study is primarily qualitative research, with a quantitative portion. A work system analysis was conducted to analyze the complicated anesthesia work system using human factors principles and identify SVs. Anesthesia providers were shadowed: (1) during general surgery cases (n = 8) exclusively using SFS and (2) during general surgery cases (n = 9) using all commercially available PFS. A proactive risk assessment focus group was followed to understand the risk of each identified SV. RESULTS: PFS are superior to SFS in terms of the simplified work processes and the reduced number and associated risk of SVs. Eight SVs were found in the PFS system versus 21 in the SFS system. An SV example with high risk in the SFS system was a medication might need to be "drawn-up during surgery while completing other requests simultaneously." This SV added cognitive complexity during anesthesiology medication delivery. However, it did not exist in the PFS system. CONCLUSIONS: The inclusion of PFS into anesthesiology medication delivery has the potential to improve system safety and work efficiency. However, there were still opportunities for further improvement by addressing the remaining SVs and newly introduced complexity. PMID- 26845140 TI - Cardiac Slo2.1 Is Required for Volatile Anesthetic Stimulation of K+ Transport and Anesthetic Preconditioning. AB - BACKGROUND: Anesthetic preconditioning (APC) is a clinically important phenomenon in which volatile anesthetics (VAs) protect tissues such as heart against ischemic injury. The mechanism of APC is thought to involve K channels encoded by the Slo gene family, and the authors showed previously that slo-2 is required for APC in Caenorhabditis elegans. Thus, the authors hypothesized that a slo-2 ortholog may mediate APC-induced cardioprotection in mammals. METHODS: A perfused heart model of ischemia-reperfusion injury, a fluorescent assay for K flux, and mice lacking Slo2.1 (Slick), Slo2.2 (Slack), or both (double knockouts, Slo2.x dKO) were used to test whether these channels are required for APC-induced cardioprotection and for cardiomyocyte or mitochondrial K transport. RESULTS: In wild-type (WT) hearts, APC improved post-ischemia-reperfusion functional recovery (APC = 39.5 +/- 3.7% of preischemic rate * pressure product vs. 20.3 +/- 2.3% in controls, means +/- SEM, P = 0.00051, unpaired two-tailed t test, n = 8) and lowered infarct size (APC = 29.0 +/- 4.8% of LV area vs. 51.4 +/- 4.5% in controls, P = 0.0043, n = 8). Protection by APC was absent in hearts from Slo2.1 mice (% recovery APC = 14.6 +/- 2.6% vs. 16.5 +/- 2.1% in controls, P = 0.569, n = 8 to 9, infarct APC = 52.2 +/- 5.4% vs. 53.5 +/- 4.7% in controls, P = 0.865, n = 8 to 9). APC protection was also absent in Slo2.x dKO hearts (% recovery APC = 11.0 +/- 1.7% vs. 11.9 +/- 2.2% in controls, P = 0.725, n = 8, infarct APC = 51.6 +/- 4.4% vs. 50.5 +/- 3.9% in controls, P = 0.855, n = 8). Meanwhile, Slo2.2 hearts responded similar to WT (% recovery APC = 41.9 +/- 4.0% vs. 18.0 +/- 2.5% in controls, P = 0.00016, n = 8, infarct APC = 25.2 +/- 1.3% vs. 50.8 +/- 3.3% in controls, P < 0.000005, n = 8). Furthermore, VA-stimulated K transport seen in cardiomyocytes or mitochondria from WT or Slo2.2 mice was absent in Slo2.1 or Slo2.x dKO. CONCLUSION: Slick (Slo2.1) is required for both VA-stimulated K flux and for the APC-induced cardioprotection. PMID- 26845141 TI - Microbiological Contamination of Drugs during Their Administration for Anesthesia in the Operating Room. AB - BACKGROUND: The aseptic techniques of anesthesiologists in the preparation and administration of injected medications have not been extensively investigated, but emerging data demonstrate that inadvertent lapses in aseptic technique may be an important contributor to surgical site and other postoperative infections. METHODS: A prospective, open, microbiological audit of 303 cases in which anesthesiologists were asked to inject all bolus drugs, except propofol and antibiotics, through a 0.2-um filter was performed. The authors cultured microorganisms, if present, from the 0.2-um filter unit and from the residual contents of the syringes used for drawing up or administering drugs. Participating anesthesiologists rated ease of use of the filters after each case. RESULTS: Twenty-three anesthesiologists each anesthetized up to 25 adult patients. The authors isolated microorganisms from filter units in 19 (6.3%) of 300 cases (3 cases were excluded), including Staphylococcus capitis, Staphylococcus warneri, Staphylococcus epidermidis, Staphylococcus haemolyticus, Micrococcus luteus/lylae, Corynebacterium, and Bacillus species. The authors collected used syringes at the end of each case and grew microorganisms from residual drug in 55 of these 2,318 (2.4%) syringes including all the aforementioned microorganisms and also Kocuria kristinae, Staphylococcus aureus, and Staphylococcus hominus. Participants' average rating of ease of use of the filter units was 3.5 out of 10 (0 being very easy and 10 being very difficult). CONCLUSIONS: Microorganisms with the potential to cause infection are being injected (presumably inadvertently) into some patients during the administration of intravenous drugs by bolus during anesthesia. The relevance of this finding to postoperative infections warrants further investigation. PMID- 26845142 TI - A Slick Way Volatile Anesthetics Reduce Myocardial Injury. PMID- 26845143 TI - Injection Rhymes with Infection? PMID- 26845144 TI - Reporting of Preclinical Research in Anesthesiology: Transparency and Enforcement. PMID- 26845145 TI - Multielemental bioimaging of tissues in children's environmental health research. AB - PURPOSE OF REVIEW: Metals play major roles in children's health and are associated with negative health outcomes via deficiency, overload, or toxicity. Constantly evolving analytical technology can provide new insight into how metal metabolism and exposure biology are intertwined in a range of biological matrices. RECENT FINDINGS: Exposure can occur prenatally as many metals cross the placental barrier. The placenta is permeable to many metal species, some through tightly regulated transporters, and others because of a limited capacity for detoxification. Postbirth, metal exposure continues to exert long-term health effects, ranging from exposure to exogenous heavy metals, such as lead, to overload of otherwise essential metals, including manganese. Increasing evidence supports the existence of critical developmental windows when susceptibility to toxicants and nutritional deficiencies is highest. Elemental imaging technology provides microspatial information on metal uptake and retention across tissue architecture, which provides important insights into exposure and biologic response. SUMMARY: Imaging the spatial distribution of elements, both essential and toxic, provides information that bulk measures cannot, including cell specific distributions and timing of exposure. PMID- 26845147 TI - Gas phase equilibrium structure of histamine. AB - The first gas electron diffraction (GED) experiment for histamine was carried out. The equilibrium structure of histamine in the gas phase was determined on the basis of the data obtained. The refinement was also supported by the rotational constants obtained in previous studies [B. Vogelsanger, et al., J. Am. Chem. Soc., 1991, 113, 7864-7869; P. Godfrey, et al., J. Am. Chem. Soc., 1998, 120, 10724-10732] and quantum chemical calculations. The proposed mechanism of tautomerization by simultaneous intermolecular transfer of hydrogens in a histamine dimer helps to explain the distribution of tautomers in different experiments. The estimations of the conformational interconversion times provided the explanation for the absence of some conformers in the rotational spectroscopy experiments. PMID- 26845146 TI - Proteinuria and hematuria in the neonate. AB - PURPOSE OF REVIEW: Neonatal proteinuria and hematuria while not common can have potentially devastating consequences if left undiagnosed and untreated. It is important to distinguish between inherited and acquired causes of proteinuria to initiate appropriate and timely treatment. With regards to hematuria, it is critical to identify true hematuria from pseudo-hematuria to balance between thorough investigation and unnecessary laboratory work up. This review provides an overview of the common causes of hematuria and proteinuria in a neonate. RECENT FINDINGS: The identification of genetic mutations in nephrotic syndrome has improved our understanding of the role of various proteins that play an important role in maintaining the glomerular filtration barrier. With the advancement in our ability to provide care for extreme premature neonates, the incidence of acute kidney injury has increased in these neonates along with proteinuria and hematuria. SUMMARY: Persistent proteinuria after neonatal acute kidney injury would be of interest in regards to the risk of developing future chronic kidney disease and hypertension. PMID- 26845148 TI - MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma. AB - OBJECTIVE: Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases. METHODS: We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE) tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real time PCR. RESULTS: All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01). MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01). No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01). CONCLUSION: In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases. PMID- 26845149 TI - End of Life Care for Patients Dying of Stroke: A Comparative Registry Study of Stroke and Cancer. AB - BACKGROUND: Although stroke is a significant public health challenge and the need for palliative care has been emphasized for these patients, there is limited data on end-of-life care for patients dying from stroke. OBJECTIVE: To study the end of-life care during the last week of life for patients who had died of stroke in terms of registered symptom, symptom management, and communication, in comparison with patients who had died of cancer. DESIGN: This study is a retrospective, comparative registry study. METHODS: A retrospective comparative registry study was performed using data from a Swedish national quality register for end-of-life care based on WHO's definition of Palliative care. Data from 1626 patients who had died of stroke were compared with data from 1626 patients who had died of cancer. Binary logistic analyses were used to calculate odds ratios, with 95% CI. RESULTS: Compared to patients who was dying of cancer, the patients who was dying of stroke had a significantly higher prevalence of having death rattles registered, but a significantly lower prevalence of, nausea, confusion, dyspnea, anxiety, and pain. In addition, the stroke group had significantly lower odds ratios for health care staff not to know whether all these six symptoms were present or not. Patients who was dying of stroke had significantly lower odds ratio of having informative communication from a physician about the transition to end-of-life care and of their family members being offered bereavement follow up. CONCLUSIONS: The results indicate on differences in end-of-life care between patients dying of stroke and those dying from cancer. To improve the end-of-life care in clinical practice and ensure it has consistent quality, irrespective of diagnosis, education and implementation of palliative care principles are necessary. PMID- 26845151 TI - When the Fight against Fungi Goes Wrong. PMID- 26845150 TI - Regulation of Stem Cell Proliferation and Cell Fate Specification by Wingless/Wnt Signaling Gradients Enriched at Adult Intestinal Compartment Boundaries. AB - Intestinal stem cell (ISC) self-renewal and proliferation are directed by Wnt/beta-catenin signaling in mammals, whereas aberrant Wnt pathway activation in ISCs triggers the development of human colorectal carcinoma. Herein, we have utilized the Drosophila midgut, a powerful model for ISC regulation, to elucidate the mechanisms by which Wingless (Wg)/Wnt regulates intestinal homeostasis and development. We provide evidence that the Wg signaling pathway, activation of which peaks at each of the major compartment boundaries of the adult intestine, has essential functions. Wg pathway activation in the intestinal epithelium is required not only to specify cell fate near compartment boundaries during development, but also to control ISC proliferation within compartments during homeostasis. Further, in contrast with the previous focus on Wg pathway activation within ISCs, we demonstrate that the primary mechanism by which Wg signaling regulates ISC proliferation during homeostasis is non-autonomous. Activation of the Wg pathway in absorptive enterocytes is required to suppress JAK-STAT signaling in neighboring ISCs, and thereby their proliferation. We conclude that Wg signaling gradients have essential roles during homeostasis and development of the adult intestine, non-autonomously controlling stem cell proliferation inside compartments, and autonomously specifying cell fate near compartment boundaries. PMID- 26845153 TI - The need to differentiate fear for energy overfeeding from future benefits of protein feeding: so much to gain! PMID- 26845152 TI - The Development of Computational Biology in South Africa: Successes Achieved and Lessons Learnt. AB - Bioinformatics is now a critical skill in many research and commercial environments as biological data are increasing in both size and complexity. South African researchers recognized this need in the mid-1990s and responded by working with the government as well as international bodies to develop initiatives to build bioinformatics capacity in the country. Significant injections of support from these bodies provided a springboard for the establishment of computational biology units at multiple universities throughout the country, which took on teaching, basic research and support roles. Several challenges were encountered, for example with unreliability of funding, lack of skills, and lack of infrastructure. However, the bioinformatics community worked together to overcome these, and South Africa is now arguably the leading country in bioinformatics on the African continent. Here we discuss how the discipline developed in the country, highlighting the challenges, successes, and lessons learnt. PMID- 26845155 TI - Growth Type and Functional Trajectories: An Empirical Study of Urban Expansion in Nanjing, China. AB - Drawing upon the Landsat satellite images of Nanjing from 1985, 1995, 2001, 2007, and 2013, this paper integrates the convex hull analysis and common edge analysis at double scales, and develops a comprehensive matrix analysis to distinguish the different types of urban land expansion. The results show that Nanjing experienced rapid urban expansion, dominated by a mix of residential and manufacturing land from 1985 to 2013, which in turn has promoted Nanjing's shift from a compact mononuclear city to a polycentric one. Spatial patterns of three specific types of growth, namely infilling, extension, and enclave were quite different in four consecutive periods. These patterns result primarily from the existing topographic constraints, as well as government-oriented urban planning and policies. By intersecting the function maps, we also reveal the functional evolution of newly-developed urban land. Moreover, both self-enhancing and mutual promotion of the newly developed functions are surveyed over the last decade. Our study confirms that the integration of a multi-scale method and multi-perspective analysis, such as the spatiotemporal patterns and functional evolution, helps us to better understand the rapid urban growth in China. PMID- 26845157 TI - Where Two Are Fighting, the Third Wins: Stronger Selection Facilitates Greater Polymorphism in Traits Conferring Competition-Dispersal Tradeoffs. AB - A major conundrum in evolution is that, despite natural selection, polymorphism is still omnipresent in nature: Numerous species exhibit multiple morphs, namely several abundant values of an important trait. Polymorphism is particularly prevalent in asymmetric traits, which are beneficial to their carrier in disruptive competitive interference but at the same time bear disadvantages in other aspects, such as greater mortality or lower fecundity. Here we focus on asymmetric traits in which a better competitor disperses fewer offspring in the absence of competition. We report a general pattern in which polymorphic populations emerge when disruptive selection increases: The stronger the selection, the greater the number of morphs that evolve. This pattern is general and is insensitive to the form of the fitness function. The pattern is somewhat counterintuitive since directional selection is excepted to sharpen the trait distribution and thereby reduce its diversity (but note that similar patterns were suggested in studies that demonstrated increased biodiversity as local selection increases in ecological communities). We explain the underlying mechanism in which stronger selection drives the population towards more competitive values of the trait, which in turn reduces the population density, thereby enabling lesser competitors to stably persist with reduced need to directly compete. Thus, we believe that the pattern is more general and may apply to asymmetric traits more broadly. This robust pattern suggests a comparative, unified explanation to a variety of polymorphic traits in nature. PMID- 26845159 TI - Finally, an extra set of hands. PMID- 26845156 TI - Gastroprotective Effects of Astragaloside IV against Acute Gastric Lesion in Rats. AB - BACKGROUND: Protection of the gastric mucosa from acute lesions induced by various irritants is a pertinent issue in the field of critical care medicine. In this study, we investigated the gastroprotective effects of astragaloside IV on acute gastric lesions in rats under stressful conditions. METHODS: Rats were randomized into six groups. Group 1 and 2 received 10% Tween 80 (vehicle). Group 3 received 20 mg/kg of omeprazole, a proton pump inhibitor. Groups 4, 5 and 6 received astragaloside IV at concentration of 1, 10, and 50 mg/kg, respectively. As a means to induce gastric lesions, Groups 2-6 were subjected to water immersion and restraint stress for 12 hours after treatment. RESULTS: Our present studies show that compared to rats in group 2, treatment with 1 to 50 mg/kg astragaloside IV significantly decreased the size of gastric lesions, MDA, TNFalpha and MCP1 levels, in addition to normalizing gastric pH, gastric mucus and SOD levels (P<0.05). Histomorphological examination confirmed that treatment with astragaloside IV elicited a dosage-dependent protective effect on the gastric mucosa. Furthermore, pretreatment with astragaloside IV resulted in significant elevations in HSP70 and reduction in Bax, along with over-expression of PLCgamma response level, which was further confirmed via immunohistochemical analysis. CONCLUSIONS: The acute gastric lesions induced are attenuated by pretreatment with astragaloside IV which is possibly due to the enhancing of the expression of HSP70 with concomitant antioxidant, anti-inflammatory and anti apoptotic capacity. PMID- 26845160 TI - HIV prevention: A 3-pronged approach. AB - HIV infection may not command the headlines it once did, but the public health threat it poses is still formidable. These steps can help us get ahead of it. PMID- 26845158 TI - Female Gender and Differences in Outcome after Isolated Coronary Artery Bypass Graft Surgery: Does Age Play a Role? AB - INTRODUCTION: Female gender is a known risk factor for early and late mortality after coronary artery bypass graft surgery (CABG). Higher age of women at operation may influence outcome, since age per se is also an important risk factor. The purpose of our study was to analyze possible gender differences in outcome after isolated CABG in different age groups to delineate the impact of female gender and age. METHODS: All patients over 60 years of age undergoing isolated CABG at our department during 2001 and 2011 were included and categorized by age into sexagenarians (2266, 16.6% women), septuagenarians (2332, 25.4% women) and octogenarians (374, 32% women) and assessed by gender for 30-day and 180-day mortality. RESULTS: Thirty-day mortality was significantly higher in women only amongst septuagenarians (7.1 vs. 4.7%, p = 0.033). Same differences apply for 180-day mortality (12.3 vs. 8.2%, p = 0.033) and estimated one-year survival (81.6 +/- 4.2 vs. 86.9 +/- 2.2%, p = 0.001). Predictive factors for 30 day mortality of septuagenarian were logistic EuroSCORE (ES) (p = 0.003), perioperative myocardial infarction (MI) (p<0.001), pneumonia (p<0.001), abnormal LV-function (p<0.04) and use of LIMA graft (p<0.001), but not female gender. However, female gender was found to be an independent predictor for 180-day mortality (HR 1.632, p = 0.001) in addition to ES, use of LIMA graft, perioperative MI, pneumonia and abnormal LV function (HR 1.013, p = 0.004; HR 0.523, p<0.001; HR 2.710, p<0.001; HR 3.238, p<0.001; HR 2.013, p<0.001). CONCLUSION: Women have a higher observed probability of early death after CABG in septuagenarians. However, female gender was not found to be an independent risk factor for 30-day, but for 180-day survival. Therefore, reduction of high impact risk factors such as perioperative MI and enhancement of LIMA use should be future goals. In view of our findings, decision for surgical revascularization should not be based on gender. PMID- 26845161 TI - Smoking cessation: What should you recommend? AB - Fifty years after a landmark report on its perils, smoking remains a major public health problem. Here's the latest on how best to help patients quit. PMID- 26845162 TI - Targeting gut flora to treat and prevent disease. AB - There's evidence to suggest that probiotics, prebiotics, and a high-fiber diet can help mange various illnesses. Here's how to translate gut flora research into practice. PMID- 26845163 TI - Severe anal pain . perianal swelling . no history of injury to the area . Dx? PMID- 26845164 TI - USPSTF urges extra step before treating hypertension. AB - Use ambulatory or at-home blood pressure measuring to confirm high readings found in the office. Vary screening intervals according to patient age and risk factors. PMID- 26845165 TI - PURLs: Aneuploidy screening: Newer noninvasive test gains traction. AB - Favorable results from the 2 studies reviewed here have prompted ACOG to recommend that cell-free DNA screening be discussed with all pregnant patients. PMID- 26845166 TI - Hard nodular lesions over the chest wall. AB - Thirteen years after undergoing a mastectomy for breast cancer, this patient developed lesions near the scar. PMID- 26845167 TI - Help Desk Answer: Is there an increased risk of GI bleeds with SSRIs? PMID- 26845169 TI - Pruritic postpartum eruption. AB - Our patient initially blamed the lesions on the surgical tape used after her C section; a skin biopsy told another story. PMID- 26845168 TI - Pulmonary Practice Pearls for Primary Care Physicians 13-part eNewsletter series. AB - The aim of this supplement is to provide an introduction to recent advances in the understanding of the impact of microorganisms on the normal and diseased lung for patients with asthma and COPD. PMID- 26845170 TI - The Histaminergic Tuberomamillary Nucleus Is Involved in Appetite for Sex, Water and Amphetamine. AB - The histaminergic system is one component of the ascending arousal system which is involved in wakefulness, neuroendocrine control, cognition, psychiatric disorders and motivation. During the appetitive phase of motivated behaviors the arousal state rises to an optimal level, thus giving proper intensity to the behavior. Previous studies have demonstrated that the histaminergic neurons show an earlier activation during the appetitive phase of feeding, compared to other ascending arousal system nuclei, paralleled with a high increase in arousal state. Lesions restricted to the histaminergic neurons in rats reduced their motivation to get food even after 24 h of food deprivation, compared with intact or sham lesioned rats. Taken together, these findings indicate that the histaminergic system is important for appetitive behavior related to feeding. However, its role in other goal-directed behaviors remains unexplored. In the present work, male rats rendered motivated to obtain water, sex, or amphetamine showed an increase in Fos-ir of histaminergic neurons in appetitive behaviors directed to get those reinforcers. However, during appetitive tests to obtain sex, or drug in amphetamine-conditioned rats, Fos expression increased in most other ascending arousal system nuclei, including the orexin neurons in the lateral hypothalamus, dorsal raphe, locus coeruleus and laterodorsal tegmental neurons, but not in the ventral tegmental area, which showed no Fos-ir increase in any of the 3 conditions. Importantly, all these appetitive behaviors were drastically reduced after histaminergic cell-specific lesion, suggesting a critical contribution of histamine on the intensity component of several appetitive behaviors. PMID- 26845171 TI - TGF-beta Type I Receptor Kinase Inhibitor EW-7197 Suppresses Cholestatic Liver Fibrosis by Inhibiting HIF1alpha-Induced Epithelial Mesenchymal Transition. AB - BACKGROUND/AIMS: Hypoxia is an environmental factor that aggravates liver fibrosis. HIF1alpha activates hepatic stellate cells (HSCs) and increases transforming growth factor-beta (TGF-beta) signaling and the epithelial mesenchymal transition (EMT), accelerating the progression of fibrosis. We evaluated the anti-fibrotic therapeutic potential of a small-molecule inhibitor of TGF-beta type I receptor kinase, EW-7197, on HIF1alpha-derived TGF-beta signaling in cholestatic liver fibrosis. METHODS: We used a bile duct ligation (BDL)-operated rat model to characterize the role of HIF1alpha-derived TGF-beta signaling in liver fibrosis. Cellular assays were performed in LX-2 cells (human immortalized HSCs). The anti-fibrotic effects of EW-7197 in liver tissues and HSCs were investigated via biochemical assays, immunohistochemistry (IHC), immunofluorescence (IF), chromatin immunoprecipitation (ChIP) assays, real-time PCR, and western blotting. RESULTS: In our BDL rat model, orally administered EW 7197 inhibited fibrosis and attenuated HIF1alpha-induced activation of HSCs and EMT in vivo. In addition, EW-7197 inhibited HIF1alpha-derived HSC activation and expression of EMT markers in LX-2 cells in vitro. CONCLUSION: This study suggests that EW-7197 exhibits potential as a treatment for liver fibrosis because it inhibits HIF1alpha-induced TGF-beta signaling. PMID- 26845173 TI - Organization principles of biological networks: An explorative study. AB - The definition of general topological principles allowing for graph characterization is an important pre-requisite for investigating structure function relationships in biological networks. Here we approached the problem by means of an explorative, data-driven strategy, building upon a size-balanced data set made of around 200 distinct biological networks from seven functional classes and simulated networks coming from three mathematical graph models. A clear link between topological structure and biological function did emerge in terms of class membership prediction (average 67% of correct predictions, p<0.0001) with a varying degree of 'peculiarity' across classes going from a very low (25%) recognition efficiency for neural and brain networks to the extremely high (80%) peculiarity of amino acid-amino acid interaction (AAI) networks. We recognized four main dimensions (principal components) as main organization principles of biological networks. These components allowed for an efficient description of network architectures and for the identification of 'not-physiological' (in this case cancer metabolic networks acting as test set) wiring patterns. We highlighted as well the need of developing new theoretical generative models for biological networks overcoming the limitations of present mathematical graph idealizations. PMID- 26845174 TI - Chemoradiotherapy with FOLFOX plus cetuximab in locally advanced oesophageal cancer: The GERCOR phase II trial ERaFOX. AB - BACKGROUND: To determine efficacy and toxicity of radiation therapy combined with oxaliplatin, 5-fluorouracil, and folinic acid (FOLFOX) and cetuximab in patients with locally advanced oesophageal cancer. PATIENTS AND METHODS: Patients with stage III oesophageal or gastro-oesophageal junction cancer were enrolled in a Simon's two-stage phase II study. Patients received FOLFOX and weekly cetuximab on week 1-10 with concurrent radiotherapy (50.4 Gy in 30 fractions) on week 5-10. Primary end-point was clinical overall response rate (ORR). An ORR rate of more than 50% was expected. RESULTS: Among the 79 included patients, clinical ORR was 77% with 40% complete responses. Median overall survival and progression-free survival were 21.6 and 11.3 months, respectively. The most common grade III-IV toxicities observed during experimental chemoimmunotherapy followed by chemoradiation included neutropenia (28%), oesophagitis (12%), rash (11%), and allergy (9%). There was one treatment-related death due to oesophagitis with gastrointestinal bleeding. CONCLUSIONS: Cetuximab-FOLFOX regimen combined with radiotherapy demonstrated its efficacy and was well tolerated. Unfortunately, these results were not confirmed in two recent phase III studies. PMID- 26845172 TI - Estrogen Enhances the Cell Viability and Motility of Breast Cancer Cells through the ERalpha-DeltaNp63-Integrin beta4 Signaling Pathway. AB - Estrogen induces ERalpha-positive breast cancer aggressiveness via the promotion of cell proliferation and survival, the epithelial-mesenchymal transition, and stem-like properties. Integrin beta4 signaling has been implicated in estrogen/ERalpha-induced tumorigenicity and anti-apoptosis; however, this signaling cascade poorly understood. DeltaNp63, an N-terminally truncated isoform of the p63 transcription factor, functions as a transcription factor of integrinbeta4 and therefore regulates cellular adhesion and survival. Therefore, the aim of the present study was to investigate the estrogen-induced interaction between ERalpha, DeltaNp63 and integrin beta4 in breast cancer cells. In ERalpha positive MCF-7 cells, estrogen activated ERalpha transcription, which induced DeltaNp63 expression. And DeltaNp63 subsequently induced integrin beta4 expression, which resulted in AKT phosphorylation and enhanced cell viability and motility. Conversely, there was no inductive effect of estrogen on DeltaNp63 integrinbeta4-AKT signaling or on cell viability and motility in ERalpha-negative MDA-MB-231 cells. DeltaNp63 knockdown abolishes these estrogen-induced effects and reduces cell viability and motility in MCF-7 cells. Nevertheless, DeltaNp63 knockdown also inhibited cell migration in MDA-MB-231 cells through reducing integrin beta4 expression and AKT phosphorylation. In conclusion, estrogen enhances ERalpha-positive breast cancer cell viability and motility through activating the ERalpha-DeltaNp63-integrin beta4 signaling pathway to induce AKT phosphorylated activation. Those findings should be useful to elucidate the crosstalk between estrogen/ER signaling and DeltaNp63 signaling and provide novel insights into the effects of estrogen on breast cancer progression. PMID- 26845175 TI - Retrospective inter- and intra-patient evaluation of trabectedin after best supportive care for patients with advanced translocation-related sarcoma after failure of standard chemotherapy. AB - AIM: Our randomised phase II study showed the clinical benefit of trabectedin compared with best supportive care (BSC) in patients with advanced translocation related sarcomas after the failure of standard chemotherapy. The aim of the present study was to evaluate efficacy and safety of trabectedin in the identical patients crossed over to trabectedin after disease progression in the BSC arm of the randomised study. PATIENTS AND METHODS: This was a single-arm study of the BSC patients of the randomised study in whom disease progressed. Trabectedin (1.2 mg/m(2)) was administered over 24 h on day 1 of a 21-d treatment cycle. The efficacy and safety of trabectedin after BSC were evaluated and retrospectively compared with the results of the randomised study. RESULTS: Thirty patients crossed over to trabectedin. Median progression-free survival (PFS) was 7.3 months (95% confidence interval [CI]: 2.9-9.1) after crossover compared with 0.9 months (95% CI: 0.9-1.0) at BSC in the randomised study. PFS in the present study was comparable to that of the trabectedin arm in the randomised study. The number of patients with growth modulation index >=1.33 was 25 (86%). Individual tumour volume was decreased in 11 patients after crossover. Adverse drug reactions (ADRs) were observed in 27 patients (96.4%). ADRs of grade III-IV were mainly bone marrow suppression and abnormal liver functions. CONCLUSION: Trabectedin was revealed to be effective and well tolerated in the identical patients crossed over to trabectedin after disease progression in BSC. The present study is registered with the Japan Pharmaceutical Information Center, number JapicCTI 121853. PMID- 26845177 TI - Thyroid endocrine status of wild European eels (Anguilla anguilla) in the Loire (France). Relationships with organic contaminant body burdens. AB - In teleost fish, thyroid function is involved in various critical physiological processes. Given the complexity of the hypothalamo-pituitary-thyroid (HPT) axis, a large number of genes and proteins can be the potential target of endocrine disrupting compounds (EDCs). The aim of this study was to evaluate, in yellow and silver European eels (Anguilla anguilla), potential effects of EDCs on thyroid status by analyzing the associations between EDC body burdens and thyroid hormones (THs). In yellow individuals, greater free T3/T4 ratios (FT3/FT4) and lower plasma FT4 levels were associated with greater concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as highlighted by significant correlations with many congeners. Few positive relationships with alkylphenols were noticed. In contrast, silver eels usually exhibited less significant correlations between THs and contaminant loads. Expression of a series of genes involved in the HPT axis was also investigated in the silver individuals. Concerning mRNA expression in silver females, some main correlations were noticed: thyroid-stimulating hormone (TSHbeta) gene expression was significantly correlated to numerous PCBs, and hepatic mRNA levels of deiodinase 2 (Deio 2) were negatively correlated to 2-hydroxyfluorene (2-OHF) and 2-naphtol (2-OHNa). Thyroid receptor (TRalpha and TRbeta) mRNA levels exhibited weak negative correlations with some PBDEs in silver females and males. Hepatic vitellogenin (Vtg) mRNA levels were detected in all silver males but at lower levels than in silver females. In males, Vtg mRNA levels were positively associated to FT4/TT4. In silver females, strong positive correlations were found between congeners of PCBs, PBDEs and PFAS suggesting potential estrogenic effects. Overall, the observed results indicate that several organic contaminants, mainly dl-, ndl-PCBs and PBDEs, could be associated with changes in thyroid homeostasis in these fish, via direct or indirect interactions with peripheral deiodination, metabolism of T4 and mechanisms involved in TSHbeta, Deio 2 and Vtg gene transcription. PMID- 26845178 TI - Regional reconstruction of flash flood history in the Guadarrama range (Central System, Spain). AB - Flash floods are a common natural hazard in Mediterranean mountain environments and responsible for serious economic and human disasters. The study of flash flood dynamics and their triggers is a key issue; however, the retrieval of historical data is often limited in mountain regions as a result of short time series and the systematic lack of historical data. In this study, we attempt to overcome data deficiency by supplementing existing records with dendrogeomorphic techniques which were employed in seven mountain streams along the northern slopes of the Guadarrama Mountain range. Here we present results derived from the tree-ring analysis of 117 samples from 63 Pinus sylvestris L. trees injured by flash floods, to complement existing flash flood records covering the last ~200years and comment on their hydro-meteorological triggers. To understand the varying number of reconstructed flash flood events in each of the catchments, we also performed a comparative analysis of geomorphic catchment characteristics, land use evolution and forest management. Furthermore, we discuss the limitations of dendrogeomorphic techniques applied in managed forests. PMID- 26845176 TI - Central HIV-1 Tat exposure elevates anxiety and fear conditioned responses of male mice concurrent with altered mu-opioid receptor-mediated G-protein activation and beta-arrestin 2 activity in the forebrain. AB - Co-exposure to opiates and HIV/HIV proteins results in enhanced CNS morphological and behavioral deficits in HIV(+) individuals and in animal models. Opiates with abuse liability, such as heroin and morphine, bind preferentially to and have pharmacological actions through MU-opioid-receptors (MORs). The mechanisms underlying opiate-HIV interactions are not understood. Exposure to the HIV-1 transactivator of transcription (Tat) protein causes neurodegenerative outcomes that parallel many aspects of the human disease. We have also observed that in vivo exposure to Tat results in apparent changes in morphine efficacy, and thus have hypothesized that HIV proteins might alter MOR activation. To test our hypothesis, MOR-mediated G-protein activation was determined in neuroAIDS relevant forebrain regions of transgenic mice with inducible CNS expression of HIV-1 Tat. G-protein activation was assessed by MOR agonist-stimulated [(35)S]guanosine-5'-O-(3-thio)triphosphate ([(35)S]GTPgammaS) autoradiography in brain sections, and in concentration-effect curves of MOR agonist-stimulated [(35)S]GTPgammaS binding in membranes isolated from specific brain regions. Comparative studies were done using the MOR-selective agonist DAMGO ([D-Ala(2), N MePhe(4), Gly-ol]-enkephalin) and a more clinically relevant agonist, morphine. Tat exposure reduced MOR-mediated G-protein activation in an agonist, time, and regionally dependent manner. Levels of the GPCR regulatory protein beta-arrestin 2, which is involved in MOR desensitization, were found to be elevated in only one affected brain region, the amygdala; amygdalar beta-arrestin-2 also showed a significantly increased association with MOR by co-immunoprecipitation, suggesting decreased availability of MOR. Interestingly, this correlated with changes in anxiety and fear-conditioned extinction, behaviors that have substantial amygdalar input. We propose that HIV-1 Tat alters the intrinsic capacity of MOR to signal in response to agonist binding, possibly via a mechanism involving altered expression and/or function of beta-arrestin-2. PMID- 26845179 TI - Environmental contamination due to shale gas development. AB - Shale gas development potentially contaminates both air and water compartments. To assist in governmental decision-making on future explorations, we reviewed scattered information on activities, emissions and concentrations related to shale gas development. We compared concentrations from monitoring programmes to quality standards as a first indication of environmental risks. Emissions could not be estimated accurately because of incomparable and insufficient data. Air and water concentrations range widely. Poor wastewater treatment posed the highest risk with concentrations exceeding both Natural Background Values (NBVs) by a factor 1000-10,000 and Lowest Quality Standards (LQSs) by a factor 10-100. Concentrations of salts, metals, volatile organic compounds (VOCs) and hydrocarbons exceeded aquatic ecotoxicological water standards. Future research must focus on measuring aerial and aquatic emissions of toxic chemicals, generalisation of experimental setups and measurement technics and further human and ecological risk assessment. PMID- 26845180 TI - Assessment of methods for simplified traffic noise mapping of small cities: Casework of the city of Valdivia, Chile. AB - In many countries such as Chile, there is scarce official information for generating accurate noise maps. Therefore, specific simplification methods are becoming a real need for the acoustic community in developing countries. Thus, the main purpose of this work was to evaluate and apply simplified methods to generate a cost-effective traffic noise map of a small city of Chile. The experimental design involved the simplification of the cartographic information on buildings by clustering the households within a block, and the classification of the vehicular traffic flows into categories to generate an inexpensive noise map. The streets have been classified according to the official road classification of the country. Segregation of vehicles from light, heavy and motorbikes is made to account for traffic flow. In addition, a number of road traffic noise models were compared with noise measurements and consequently the road traffic model RLS-90 was chosen to generate the noise map of the city using the Computer Aided Noise Abatement (CadnaA) software. It was observed a direct dependence between noise levels and traffic flow versus each category of street used. The methodology developed in this study appears to be convenient in developing countries to obtain accurate approximations to develop inexpensive traffic noise maps. PMID- 26845181 TI - Dissipation of a commercial mixture of polyoxyethylene amine surfactants in aquatic outdoor microcosms: Effect of water depth and sediment organic carbon. AB - This study optimized existing analytical approaches and characterized the effect of sediment total organic carbon (0.05-2.05% TOC), and water depth (15, 30, and 90cm) on the fate of MON 0818, a commercial mixture of polyoxyethylene amine surfactants (POEAs), in outdoor microcosms. Mixtures of POEAs are commonly used as adjuvants in commercial herbicide formulations containing glyphosate. Until recently, analytical methods sensitive enough to monitor environmental concentrations of POEAs in aquatic systems were not available. After optimizing recently developed analytical methods, we found that the combined use of accelerated solvent extraction (ASE) and liquid chromatography-tandem mass spectrometry provided a reliable approach for determining the concentration of sediment-adsorbed POEAs. The surfactant showed strong affinity for sediment materials, with low maximum recoveries by ASE of 52%. Under microcosm conditions, water depth or sediment characteristics did not significantly affect the water column half-life of POEA, which ranged from 3.2 to 5.3h. Binding of POEAs to suspended solids was observed, which dissipated via one- or two-phase exponential decay; when two-phase decay occurred, fast phase half-life values ranged from 0.71 to 1.3h and slow-phase values ranged from 18 to 44h. Concentrations of POEA increased in sediment shortly after application and decreased over the study period with a half-life of 5.8 to 71d. The concentrations of POEAs in the sediment of the shallow (15cm) ponds dissipated following a two-phase exponential decay model with an initial fast-phase half-life of 1.1 to 8.9d and a slower second-phase half-life of 21d. Our results suggest that aquatic organisms are unlikely to be exposed to POEAs in aqueous phase for periods of more than a few hours following an over-water application, and that sediment is a significant sink for POEAs in aquatic systems. PMID- 26845182 TI - Soil properties, greenhouse gas emissions and crop yield under compost, biochar and co-composted biochar in two tropical agronomic systems. AB - The addition of organic amendments to agricultural soils has the potential to increase crop yields, reduce dependence on inorganic fertilizers and improve soil condition and resilience. We evaluated the effect of biochar (B), compost (C) and co-composted biochar (COMBI) on the soil properties, crop yield and greenhouse gas emissions from a banana and a papaya plantation in tropical Australia in the first harvest cycle. Biochar, compost and COMBI organic amendments improved soil properties, including significant increases in soil water content, CEC, K, Ca, NO3, NH4 and soil carbon content. However, increases in soil nutrient content and improvements in physical properties did not translate to improved fruit yield. Counter to our expectations, banana crop yield (weight per bunch) was reduced by 18%, 12% and 24% by B, C and COMBI additions respectively, and no significant effect was observed on the papaya crop yield. Soil efflux of CO2 was elevated by addition of C and COMBI amendments, likely due to an increase in labile carbon for microbial processing. Our data indicate a reduction in N2O flux in treatments containing biochar. The application of B, C and COMBI amendments had a generally positive effect on soil properties, but this did not translate into a crop productivity increase in this study. The benefits to soil nutrient content, soil carbon storage and N2O emission reduction need to be carefully weighed against potentially deleterious effects on crop yield, at least in the short-term. PMID- 26845183 TI - Using stable isotopes to determine seasonal variations in water uptake of summer maize under different fertilization treatments. AB - Fertilization and water both affect root water uptake in the nutrient and water cycle of the Soil-Plant-Atmosphere-Continuum (SPAC). In this study, dual stable isotopes (D and (18)O) were used to determine seasonal variations in water uptake patterns of summer maize under different fertilization treatments in Beijing, China during 2013-2014. The contributions of soil water at different depths to water uptake were quantified by the MixSIAR Bayesian mixing model. Water uptake was mainly sourced from soil water in the 0-20cm depth at the seeding (67.7%), jointing (60.5%), tasseling (47.5%), dough (41.4%), and harvest (43.9%) stages, and the 20-50cm depth at the milk stage (32.8%). Different levels of fertilization application led to considerable differences in the proportional contribution of soil water at 0-20cm (6.0-58.5%) and 20-50cm (6.1-26.3%). There was little difference of contributions in the deep layers (50-200cm) among treatments in 2013, whereas differences were observed in 50-90cm at the milk stage and 50-200cm at the dough stage during 2014. The main water uptake depth was concentrated in the upper soil layers (0-50cm) during the wet season (2013), whereas a seasonal drought in 2014 promoted the contribution of soil water in deep layers. The contribution of soil water was significantly and positively correlated with the proportions of root length (r=0.753, p<0.01). The changes of soil water distribution were consistent with the seasonal variation in water uptake patterns. The present study identified water sources for summer maize under varying fertilization treatments and provided scientific implications for fertilization and irrigation management. PMID- 26845184 TI - Inexistence of permafrost at the top of the Veleta peak (Sierra Nevada, Spain). AB - A 114.5m deep drilling was carried out in August 2000 in the bedrock of the Veleta peak, at 3380m in the massif of Sierra Nevada, Southern Spain. The objective of this work is to analyse temperatures at the first 60m depth of this drilling from September 2002 to August 2013 based on 11 UTL-1 thermal loggers located at different depths, together with air temperatures at the summit of the Veleta peak. Permanent negative temperatures have not been detected in the borehole, which shows evidence of the absence of widespread permafrost conditions nowadays in the highest lands of this massif. Bedrock temperatures oscillated between 3.2 degrees C at 0.6m depth and 2 degrees C at 20m below the surface. The largest temperature ranges were recorded on the most external sensors until 1.2m depth, where values reached 22.3 degrees C. Seasonal temperature variations were significant until 10m depth. The thickness of the seasonal frozen layer was highly variable (0.6-2m) and dependent on annual climate conditions. The mean air temperature at the Veleta peak increased by 0.12 degrees C during the study period. Bedrock temperatures followed diverging trends: a drop of 0.3-0.4 degrees C down to 0.6m depth, a decrease of up to 0.7 degrees C between 4 and 10m, thermal stability at 20m and a rise of 0.2 degrees C that occurred in 2009 at the deepest sensor at 60m. The calculation of the thermal wave damping in the subsoil of the Veleta peak has allowed for quantifying the thermal diffusivity of the rock as (7.05+/-0.03)10(-7)m(2)/s, which means that the external climate signal arrives with an 8.5-year lag to the sensor at 60m deep. This allows to deduce a trend change in the climate of the area, moving from warmer conditions towards a trend of cooling from 2006 to 2007. PMID- 26845185 TI - Effect of different rates of spent mushroom substrate on the dissipation and bioavailability of cymoxanil and tebuconazole in an agricultural soil. AB - Physicochemical methods to immobilize pesticides in vulnerable soils are currently being developed to prevent water contamination. Some of these methods include the use of different organic residues to modify soils because they could limit the transport of pesticides and/or facilitate their dissipation. Spent mushroom substrate (SMS) may be used for these purposes. Accordingly a study was conducted under laboratory conditions to know the dissipation and bioavailability of the fungicides cymoxanil and tebuconazole over time in a vineyard soil amended with two rates of spent mushroom substrate (SMS) (5% and 50% (w/w)), selected to prevent the diffuse or point pollution of soil. The dissipation of cymoxanil was more rapid than that of tebuconazole in the different soils studied. The dissipation rate was higher in the amended soil than in the unamended one for both compounds, while no significant differences were observed between the amended soils in either case. An apparent dissipation occurred in the amended soil due to the formation of non-extractable residues. Bound residues increased with incubation time for tebuconazole, although a proportion of this fungicide was bioavailable after 303days. The major proportion of cymoxanil was tightly bound to the amended soil from the start, although an increasing fraction of bound fungicide was bioavailable for mineralization. Soil dehydrogenase activity was significantly affected by SMS application and incubation time; however, it was not significantly modified by fungicide application. The significance of this research suggests that SMS applied at a low or high rate to agricultural soil can be used to prevent both the diffuse or point pollution of soil through the formation of non-extractable residues, although more research is needed to discover the time that fungicides remain adsorbed into the soil decreasing either bioavailability (tebuconazole) or mineralization (cymoxanil) in SMS-amended soils. PMID- 26845186 TI - Properties of biochar-amended soils and their sorption of imidacloprid, isoproturon, and atrazine. AB - Biochars produced from rice straw, wheat straw and swine manure at 300, 450 and 600 degrees C were added to soil at 1, 5, 10, or 20% levels to determine whether they would predictably reduce the pore water concentration of imidacloprid, isoproturon, and atrazine. The sorption capacity of the mixtures increased with increasing biochar amounts. The enhanced sorption capacity could be attributed to the increased organic carbon (OC) content and surface area (SA) as well as the decreased hydrophobicity. Biochar dominated the overall sorption when its content was above 5%. The OC contents of the mixtures with 10% and 20% biochar were generally lower than the predicted values. This implies possible interaction between soil components and biochar and/or the effect of biochar oxidation. For soils amended with biochars produced at 300 degrees C, the N2 SA (N2-SA) values were underestimated. The predicted CO2 SA (CO2-SA) values of the mixtures at the biochar content of 10% and 20% were generally higher than the experimental values. Sorption of imidacloprid to the soils amended with biochar at 10% and 20% levels, excluding the soils amended with rice (SR300) and wheat (SW300) straw derived biochar produced at 300 degrees C, was lower than the predicted value. For SR300 and SW300, the intrinsic sorption capacity of biochar was enhanced by 1.3-5.6 times, depending on the biochar, solute concentration, and biochar dose. This study indicates that biochars would be helpful to stabilize the soil contaminated with imidacloprid, isoproturon, and atrazine, but the sorption capacity of the mixtures could exceed or fall short of predicted values without assuming a cross-effect between soil and biochar. PMID- 26845187 TI - Pressure of non-professional use of pesticides on operators, aquatic organisms and bees in Belgium. AB - Various studies focus on professional pesticide use, whereas pressure of non professional use on human and the environment is often neglected. In this study, an attempt was made to estimate the pressure of non-professional use of pesticides on operators, aquatic organisms and bees in Belgium based on sales figures and by using three exposure models. A classification in non-professional use was made based on type of pesticide, application method and on intensity of non-professional use. Pressure of non-professional use on operators is highest for intensive operators, caused by the use of insecticides in an aerosol spray can. Pressure of non-professional pesticides on aquatic life is mainly generated by the use of herbicides. The aerosol spray induces the highest pressure whereas the trigger application hardly affects operator and environmental exposure. The ordinary non-professional user generates most pressure on aquatic organisms. Pressure of non-professional pesticides on bees is mainly caused by the use of insecticides, especially the active substance imidacloprid in combination with the aerosol spray can application method applied by an intensive operator. In general, both total usage (kg) and pressure of pesticides decreased for the period 2005 to 2012 due to efforts made by the government and industry. The results of this study suggest to pay special attention to aerosol spray applications and the non-professional use of insecticides. PMID- 26845188 TI - Bioaccumulation and human health risk assessment of DDT and other organochlorine pesticides in an apex aquatic predator from a premier conservation area. AB - With the second highest gross domestic product in Africa, South Africa is known to have a high pesticide usage, including the highly persistent and banned group of organochlorine pesticides (OCPs). South Africa is also one of few countries to still actively spray DDT as malaria vector control. The aim of the study was to determine the degree to which aquatic biota in selected rivers of the world renowned Kruger National Park (KNP) are exposed to by use of OCPs in the catchments outside the KNP and how this exposure relates to human health. Tigerfish (Hydrocynus vittatus) are economically important apex predators and was selected as bioindicator for this study. Fish were sampled from the KNP sections of the Luvuvhu, Letaba and Olifants rivers during the high and low flow periods from 2010 to 2011 within the KNP and 19 OCPs were determined in muscle tissue using GC-ECD techniques. Significant flow related and spatial OCP bioaccumulation was observed. Tigerfish from the Luvuvhu River displayed the highest OCP bioaccumulation. Concentrations of the majority of the OCPs including the DDTs were the highest levels ever recorded from South African freshwater systems and in many cases the concentrations were higher than most contaminated areas from around the world. The concentrations found in H. vittatus muscle also exceeded maximum residue levels in edible fat as set by the European Union. The health risk assessment also demonstrated that the levels of OCPs pose very high cancer risks to the local populations consuming tigerfish, as high as 2 in 10 increased risk factor. This is of concern not only when managing the water resources of the conservation area but also for surrounding communities consuming freshwater fish. Contaminants enter the park from outside the borders and pose potential risks to the mandated conservation of aquatic biota within the KNP. PMID- 26845189 TI - An insight into the drinking-water access in the health institutions at the Saharawi refugee camps in Tindouf (Algeria) after 40years of conflict. AB - Drinking water access in the Saharawi refugee camps located in the Algerian desert is a challenge that is still an on-going problem after 40years of conflict. This work presents an analysis of the situation with emphasis on the water supply in health institutions (quantity and quality) including both sanitary inspections and a comprehensive water quality study. Results from sanitary inspections show that only half of the water supply installations at the hospitals are in adequate conditions and the rest present high risk of microbiological contamination. Water access in small medical community centres on the other hand present issues related to the non-availability of food-grade water tanks for the institutions (70%), the use of small 10l containers as the main water supply (40%), poor maintenance (60% under antihygienic conditions and 30% with damaged covers), and insufficient chlorine levels that prevent microbiological contamination. Regarding water quality analyses, raw water supply in Smara, El Aiun and Awserd camps present high conductivity and high levels of fluoride, chloride, nitrate and sulphate, but dropping to normal levels within the drinking-water standards after water treatment via reverse osmosis plants. But for the case of El Aiun and Awserd, the reverse osmosis plant only provides treated water to the population each 20days, so the population receives raw water directly and health risks should be evaluated. Finally, Dakhla water supply is the best in terms of physico-chemical parameters quality, currently providing safe drinking water after a chlorination stage. In summary, drinking water access has improved dramatically in the last years due to the efforts of local and international authorities but several issues remain to be solved: access to treated water for all the population, improved water quality controls (especially in Dakhla), expansion of distribution networks, and adequate storage systems and maintenance. PMID- 26845190 TI - Multicenter Study of Sexual Functioning in Spouses/Partners of Persons With Traumatic Brain Injury. AB - OBJECTIVE: To investigate sexual functioning and its predictors in spouses/partners of persons with traumatic brain injury (TBI). DESIGN: Inception cohort survey. SETTING: Community. PARTICIPANTS: Persons (N=70) with complicated mild to severe TBI admitted to 1 of 6 participating TBI Model Systems inpatient rehabilitation units and their spouses/partners who were both living in the community and assessed 1 year after injury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Derogatis Interview for Sexual Functioning Self-Report; Global Sexual Satisfaction Index. RESULTS: Twenty percent of spouses/partners of persons with TBI reported sexual dysfunction, and 44% reported dissatisfaction with sexual functioning. Sixty-two percent of spouses/partners reported a decrease in sexual activity during the year postinjury, 34% reported a decrease in sexual drive or desire, and 34% indicated that sexuality was less important in comparison to preinjury. The sexual functioning of spouses/partners of persons with TBI was highly associated with the sexual functioning of the person with TBI. Age of spouses/partners and sexual functioning in persons with the TBI were significant predictors of spouses'/partners' sexual functioning, even after controlling for sex of partners and the physical, cognitive, participation, and sexual functioning of the persons with injury. CONCLUSIONS: Greater sexual dysfunction in spouses/partners was associated with older age and with poorer sexual functioning in the person with injury. Rehabilitation professionals should provide education on the potential impact of TBI on sexual functioning for both persons with TBI and their spouses/partners, and integrate the assessment of sexual functioning into their clinical assessment, making appropriate referrals for therapy. PMID- 26845191 TI - A Randomized Phase II Study Adding Axitinib to Pemetrexed-Cisplatin in Patients with Malignant Pleural Mesothelioma: A Single-Center Trial Combining Clinical and Translational Outcomes. AB - INTRODUCTION: Mesothelioma often presents with a high vessel count and increased vascular growth factors levels. Interference with angiogenesis may therefore improve outcome. This study reports on clinical and translational parameters in patients treated with the small molecule tyrosine kinase inhibitor axitinib and chemotherapy. METHODS: Chemonaive patients with mesothelioma were eligible. Patients received pemetrexed (500 mg/m(2) every 3 weeks) and cisplatin (75 mg/m(2) every 3 weeks) and were randomized to receive axitinib daily (two 5-mg tablets on days 2-19) or observation. Before treatment and after three cycles of chemotherapy, a thoracoscopy was performed to evaluate vascular changes. RESULTS: Twenty-five patients were randomized after a successful lead-in with six patients who received axitinib. Median follow-up was 45 months. In all but one patient, it was feasible to perform a second thoracoscopy. However, there was more grade 3 or 4 neutropenia leading to pneumonia in the axitinib group. The rates of partial response and stable disease in the axitinib arm were 36% and 43% compared with 18% and 73% in the chemotherapy-only arm. Median progression-free survival and overall survival (5.8 and 18.9 months versus 8.3 and 18.5 months) were not different between the two groups. Axitinib reduced vessel number and vessel immaturation. Yet, the mRNA levels of a number of vascular growth factors, their receptors, serum VEGF levels, and activation of tissue vascular endothelial growth factor receptor 2 were increased. Gene expression of platelet-derived growth factor receptor beta, fms-related tyrosine kinase 1, and fms-related tyrosine kinase 4 even correlated with outcome. CONCLUSIONS: Axitinib was well tolerated in combination with cisplatin and pemetrexed. Despite the lack of a clinical benefit, axitinib reduced angiogenesis. Whether changes in differentially expressed growth factors in tissue and serum may serve as a biomarker needs further investigation. PMID- 26845192 TI - The Role of Tumor-Infiltrating Lymphocytes in Development, Progression, and Prognosis of Non-Small Cell Lung Cancer. AB - A malignant tumor is not merely an accumulation of neoplastic cells, but constitutes a microenvironment containing endothelial cells, fibroblasts, structural components, and infiltrating immune cells that impact tumor development, invasion, metastasis, and outcome. Hence, the evolution of cancers reflects intricate cellular and molecular interactions between tumor cells and constituents of the tumor microenvironment. Recent studies have shed new light on this complex interaction between tumor and host immune cells and the resulting immune response. The composition of the immune microenvironment differs across patients as well as in cancers of the same type, including various populations of T cells, B cells, dendritic cells, natural killer cells, myeloid-derived suppressor cells, neutrophils, and macrophages. The type, density, location, and organization of immune cells within solid tumors define the immune contexture, which has proved to be a major determinant of tumor characteristics and patient outcome. Lung cancer consists mostly of non-small cell lung cancer (85%); it is our most deadly malignant disease, with the 5-year survival rate being merely 15%. This review focuses on the immune contexture; the tumor-suppressing roles of tumor-infiltrating lymphocytes; and the relevance of this immune contexture for cancer diagnostics, prognostication, and treatment allocation, with an emphasis on non-small cell lung cancer. PMID- 26845193 TI - Successful Immunotherapy against a Transplantable Mouse Squamous Lung Carcinoma with Anti-PD-1 and Anti-CD137 Monoclonal Antibodies. AB - INTRODUCTION: Anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (PD-L1) antagonist monoclonal antibodies (mAbs) against metastatic non-small cell lung cancer with special efficacy in patients with squamous cell lung cancer are being developed in the clinic. However, robust and reliable experimental models to test immunotherapeutic combinations in squamous lung tumors are still lacking. METHODS: We generated a transplantable squamous cell carcinoma cell line (UN-SCC680AJ) from a lung tumor induced by chronic N-nitroso tris-chloroethylurea mutagenesis in A/J mice. Tumor cells expressed cytokeratins, overexpressed p40, and lacked thyroid transcription factor 1, confirming the squamous lineage reported by histological analysis. More than 200 mutations found in its exome suggested potential for antigenicity. Immunocompetent mice subcutaneously implanted with this syngeneic cell line were treated with anti CD137 and/or anti-PD-1 mAbs and monitored for tumor growth/progression or assessed for intratumoral leukocyte infiltration using immunohistochemical analysis and flow cytometry. RESULTS: In syngeneic mice, large 12-day-established tumors derived from the transplantable cell line variant UN-SCC680AJ were amenable to curative treatment with anti-PD-1, anti-PD-L1, or anti-CD137 immunostimulatory mAbs. Single-agent therapies lost curative efficacy when treatment was started beyond day +17, whereas a combination of anti-PD-1 plus anti-CD137 achieved complete rejections. Tumor cells expressed weak baseline PD L1 on the plasma membrane, but this could be readily induced by interferon-gamma. Combined treatment efficacy required CD8 T cells and induced a leukocyte infiltrate in which T lymphocytes co-expressing CD137 and PD-1 were prominent. CONCLUSIONS: These promising results advocate the use of combined anti-PD-1/PD-L1 plus anti-CD137 mAb immunotherapy for the treatment of squamous non-small cell lung cancer in the clinical setting. PMID- 26845194 TI - Lazarus-Type Response to Crizotinib in a Patient with Poor Performance Status and Advanced MET Exon 14 Skipping Mutation-Positive Lung Adenocarcinoma. PMID- 26845195 TI - Molecular and cellular mechanisms involved in leg joint morphogenesis. AB - In summary, the patterning of the presumptive leg depends on gradients of Dpp and Wg morphogens, which lead to the establishment of the proximo-distal axis marked by the expression of Hth, Dac and Dll in broad domains along the leg. Then, EGFR signaling specifies the tarsal region by regulating the expression of tarsal gap genes in different tarsal segments. This patterning is closely linked to the formation of rings of Notch activation in the distal part of each leg segment. These rings of Notch activation are further regulated by different mechanisms: (1) the maintenance of a sharp border of Dl expression, (2) the inhibition of N activation in cells located proximally to the ligands, thus restricting N activity specifically to the distal part of cells. This localised activation of Notch induces the expression of Dysfusion which controls the expression of both pro-apoptotic genes and RhoGTPase regulators. Finally, apoptotic cells appear within the pro-apoptotic domain, and while dying, generate a transient pulling force. This force constitutes a mechanical signal that propagates to the rest of the tissue and triggers cytoskeleton reorganisation specifically in the presumptive fold, where RhoGTPase regulators are expressed. Altogether, this complex array of patterning and signaling leads to precise cellular mapping of the developing leg to correctly position local cell shape modifications, inducing tissue folding. PMID- 26845197 TI - The functional interaction between abaecin and pore-forming peptides indicates a general mechanism of antibacterial potentiation. AB - Long-chain proline-rich antimicrobial peptides such as bumblebee abaecin show minimal activity against Gram-negative bacteria despite binding efficiently to specific intracellular targets. We recently reported that bumblebee abaecin interacts with Escherichia coli DnaK but shows negligible antibacterial activity unless it is combined with sublethal doses of the pore-forming peptide hymenoptaecin. These two bumblebee peptides are co-expressed in vivo in response to a bacterial challenge. Here we investigated whether abaecin interacts similarly with pore-forming peptides from other organisms by replacing hymenoptaecin with sublethal concentrations of cecropin A (0.3 MUM) or stomoxyn (0.05 MUM). We found that abaecin increased the membrane permeabilization effects of both peptides, confirming that it can reduce the minimal inhibitory concentrations of pore-forming peptides from other species. We also used atomic force microscopy to show that 20 MUM abaecin combined with sublethal concentrations of cecropin A or stomoxyn causes profound structural changes to the bacterial cell surface. Our data indicate that the potentiating functional interaction between abaecin and pore-forming peptides is not restricted to specific co-expressed peptides from the same species but is likely to be a general mechanism. Combination therapies based on diverse insect-derived peptides could therefore be used to tackle bacteria that are recalcitrant to current antibiotics. PMID- 26845198 TI - Improving the quantity, quality and transparency of data used to derive radionuclide transfer parameters for animal products. 1. Goat milk. AB - Under the MODARIA (Modelling and Data for Radiological Impact Assessments Programme of the International Atomic Energy Agency), there has been an initiative to improve the derivation, provenance and transparency of transfer parameter values for radionuclides. The approach taken for animal products is outlined here and the first revised table for goat milk is provided. Data from some references used in TRS 472 were removed and reasons given for removal. Particular efforts were made to improve the number of CR (concentration ratio) values which have some advantages over transfer coefficients. There is little difference in most of the new CR and Fm (transfer coefficient) values for goat milk compared with those in TRS 472. In TRS 472, 21 CR values were reported for goat milk. In the 2015 dataset for goat milk CR values for a further 14 elements are now included. The CR and Fm values for only one element (Co) were removed. PMID- 26845196 TI - Actomyosin ring driven cytokinesis in budding yeast. AB - Cytokinesis is the final process in the cell cycle that physically divides one cell into two. In budding yeast, cytokinesis is driven by a contractile actomyosin ring (AMR) and the simultaneous formation of a primary septum, which serves as template for cell wall deposition. AMR assembly, constriction, primary septum formation and cell wall deposition are successive processes and tightly coupled to cell cycle progression to ensure the correct distribution of genetic material and cell organelles among the two rising cells prior to cell division. The role of the AMR in cytokinesis and the molecular mechanisms that drive AMR constriction and septation are the focus of current research. This review summarizes the recent progresses in our understanding of how budding yeast cells orchestrate the multitude of molecular mechanisms that control AMR driven cytokinesis in a spatio-temporal manner to achieve an error free cell division. PMID- 26845199 TI - Construction and characterization of human oral mucosa equivalent using hyper-dry amniotic membrane as a matrix. AB - BACKGROUND: Human amniotic membrane(HAM) as a graft material has been used in various fields. Hyper-dry amniotic membrane (HD-AM) is a novel dried amniotic membrane that is easy to handle and can be preserved at room temperature without time limitation. The purpose of this study was to investigate the useful properties of HD-AM in reconstruction of the oral mucosa. METHODS: Human oral keratinocytes were isolated and seeded on HD-AM in serum-free culture system. Oral mucosa equivalent (OME) was developed and transplanted onto full-thickness wound on athymic mice. The wound healing was analyzed and the OME both before and after transplantation was analyzed with hematoxylin-eosin staining and immunohistochemical staining for Cytokines 10 (CK10), Cytokines 16 (CK16), and Ivolucrin (IVL). RESULTS: Oral keratinocytes spread and proliferated well on HD AM. Two weeks after air-lifting, OME had formed with good differentiation and morphology. We confirmed immunohistochemically that the expression of CK10 was positive in all suprabasal layers, as was CK16 in the upper layers, while IVL was present in all cell layers. Three weeks after transplantation to athymic mice, the newly generated tissue had survived well with the smallest contraction. The epithelial cells of newly generated tissue expressed CK10 throughout in all suprabasal layers, IVL was mainly in the granular layer, and CK16 positive cells were observed in all spinous layer and granular layer but were not expressed in the mouse skin, all of which were similar to native gingival mucosa. CONCLUSIONS: The OME with HD-AM as a matrix revealed a good morphology and stable wound healing. This study demonstrates that HD-AM is a useful and feasible biomaterial for oral mucosa reconstruction. PMID- 26845200 TI - A chiral LC-MS/MS method for the stereospecific determination of efonidipine in human plasma. AB - Efonidipine hydrochloride is a new generation dihydropyridine Ca(2+) channel blocker designed to inhibit both T-type and L-type Ca(2+) channels. Efonidipine possesses a chiral carbon and is clinically administered as a racemate. In the present study, an enantioselective and sensitive LC-MS/MS method of determining efonidipine enantiomers in human plasma was developed and validated to characterize the stereoselective pharmacokinetics. Plasma samples were processed by liquid-liquid extraction (LLE). Chiral separation was optimized on a CHIRALPAK((r)) ID column using an isocratic mobile phase of acetonitrile/water (60:40, v/v). Detection was using MS in multiple reaction monitoring (MRM) mode, using the transitions of m/z 632.3->91.1 for efonidipine enantiomers, and m/z 493.3->117.2 for cilnidipine (internal standard). The calibration curves were linear over 0.100-20.0 ng/mL for each enantiomer. The lower limit of quantification (LLOQ) for each enantiomer was established at 0.100 ng/mL. Intra- and inter-day precisions were less than 12.1% for each enantiomer in terms of relative standard deviation (RSD), and accuracies were between -5.0% and 5.0% in terms of relative error (RE) for each enantiomer. No chiral inversion was observed during sample storage, preparation procedure and analysis. The validated method was successfully applied to a stereoselective pharmacokinetic study of efonidipine in healthy subjects after oral administration of 40 mg (20 mg * 2) efonidipine hydrochloride tablets. PMID- 26845201 TI - Simultaneous quantification of neuroactive dopamine serotonin and kynurenine pathway metabolites in gender-specific youth urine by ultra performance liquid chromatography tandem high resolution mass spectrometry. AB - Neuroactive metabolites in dopamine, serotonin and kynurenine metabolic pathways play key roles in several physiological processes and their imbalances have been implicated in the pathophysiology of a wide range of disorders. The association of these metabolites' alterations with various pathologies has raised interest in analytical methods for accurate quantification in biological fluids. However, simultaneous measurement of various neuroactive metabolites represents great challenges due to their trace level, high polarity and instability. In this study, an analytical method was developed and validated for accurately quantifying 12 neuroactive metabolites covering three metabolic pathways in youth urine by ultra performance liquid chromatography coupled to electrospray tandem high resolution mass spectrometry (UPLC-ESI-HRMS/MS). The strategy of dansyl chloride derivatization followed by solid phase extraction on C18 cartridges were employed to reduce matrix interference and improve the extraction efficiency. The reverse phase chromatographic separation was achieved with a gradient elution program in 20 min. The high resolution mass spectrometer (Q Exactive) was employed, with confirmation and quantification by Target-MS/MS scan mode. Youth urine samples collected from 100 healthy volunteers (Female:Male=1:1) were analyzed to explore the differences in metabolite profile and their turnover between genders. The results demonstrated that the UPLC-ESI-HRMS/MS method is sensitive and robust, suitable for monitoring a large panel of metabolites and for discovering new biomarkers in the medical fields. PMID- 26845202 TI - Feasibility of wavelength dispersive X-ray fluorescence spectrometry for the determination of metal impurities in pharmaceutical products and dietary supplements in view of regulatory guidelines. AB - The aim of this study was to investigate the feasibility of Wavelength Dispersive X-ray Fluorescence (WDXRF) spectrometry for the measurement of As, Cd, Cr, Cu, Hg, Ir, Mn, Mo, Ni, Os, Pb, Pd, Pt, Rh, Ru and V impurities in pharmaceuticals and dietary supplements, in view of the requirements by EMA and USP for the measurement of elemental impurities in drug products and according to the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH guidelines). For that purpose, a 4 kW WDXRF spectrometer (S4 Pioneer, Bruker AXS) was used after system calibration. The linearity of the method was demonstrated by correlation coefficients in excess of 0.9 and by appropriate test of lack of fit, except for Cd, Hg, Pd, V and As, which were excluded from analysis. The calculated limits of detection and quantification were in the ranges 0.6-5.4 MUg/g and 1.7-16.4 MUg/g meeting defined acceptance criteria, except for Pb. The accuracy of the method, determined by the percent recovery (R) of known amounts of each element added to a selected drug, at 3 different concentration levels, was in the acceptance range 70-150% except for Os and Pt, in which case R was marginally outside that range. The repeatability of the method, assessed as the % residual standard deviation (%RSD) of 3 replicate measurements at 3 concentration levels, produced %RSD values lower than 20%, as required. These results show that the WDXRF method complies with the validation requirements defined by the European Pharmacopeia for Cu, Cr, Ir, Mn, Mo, Ni, Os, and Pt, and by the United States Pharmacopeia for Ir, Ni, Os and Pt. Therefore, it may be an alternative to the compendial analytical procedures recommended for such elements. The novelty of the present work is the application of WDXRF to final medicines and not only to active pharmaceutical ingredients and/or excipients. PMID- 26845203 TI - Rapid characterization of Ziziphi Spinosae Semen by UPLC/Qtof MS with novel informatics platform and its application in evaluation of two seeds from Ziziphus species. AB - A strategy for rapid identification of target and non-target components from traditional Chinese medicines (TCMs) extracts were proposed by utilizing the UNIFI informatics platform for the computer-assisted UPLC/Qtof MS data analyses. Ziziphi Spinosae Semen (ZSS) contains various bioactive chemical ingredients, such as flavonoids, saponins, alkaloids and terpenes. Currently, there is no method that allows rapid and comprehensive identification of these multiple components. The rapid identification of chemical components in ZSS was successfully achieved with this strategy. As a result, 60 target components were identified and 53 non-target components were characterized. Among them, chemical structures of 40 new components were deduced based on their characteristic MS fragmentation patterns. In addition, the chemical ingredients of Ziziphi Mauritianae Semen (ZMS), which is often used as substitution of ZSS, were also investigated with the same strategy. A total of 132 chemical components were identified from these two plants, including 7 additional non-target new components. It demonstrated that this strategy not only facilitated an efficient protocol for the screening and identification of target components, but also offered a new perspective on discovering non-target components in TCMs or other herbal medicines. Furthermore, 48 components were selected for semi-quantitative analyses to evaluate the difference in chemical ingredients between these two seeds of Ziziphus species. The results showed that ZSS enriched many saponins, while ZMS contained few saponins. On the contrary, many cyclopeptide alkaloids could be detected in ZMS with high content, but rare in ZSS. These results can be used for the differentiation between ZSS and its adulterant (ZMS), and also to set a scientific foundation for the establishment of quality control of ZSS. PMID- 26845204 TI - 13C solid-state NMR analysis of the most common pharmaceutical excipients used in solid drug formulations, Part I: Chemical shifts assignment. AB - Solid-state NMR is an excellent and useful method for analyzing solid-state forms of drugs. In the (13)C CP/MAS NMR spectra of the solid dosage forms many of the signals originate from the excipients and should be distinguished from those of active pharmaceutical ingredient (API). In this work the most common pharmaceutical excipients used in the solid drug formulations: anhydrous alpha lactose, alpha-lactose monohydrate, mannitol, sucrose, sorbitol, sodium starch glycolate type A and B, starch of different origin, microcrystalline cellulose, hypromellose, ethylcellulose, methylcellulose, hydroxyethylcellulose, sodium alginate, magnesium stearate, sodium laurilsulfate and Kollidon((r)) were analyzed. Their (13)C CP/MAS NMR spectra were recorded and the signals were assigned, employing the results (R(2): 0.948-0.998) of GIPAW calculations and theoretical chemical shifts. The (13)C ssNMR spectra for some of the studied excipients have not been published before while for the other signals in the spectra they were not properly assigned or the assignments were not correct. The results summarize and complement the data on the (13)C ssNMR analysis of the most common pharmaceutical excipients and are essential for further NMR studies of API excipient interactions in the pharmaceutical formulations. PMID- 26845206 TI - [The mercy in the health care relationship]. AB - In this article, the author discusses the topic of mercy, trying to focus on the ethical-practical aspects in the health care relationship. The limits of the medical paternalism and of the health care model based on the person's autonomy are discussed in order to propose mercy as the new dimension of the health care alliance. PMID- 26845205 TI - [Incremental approach to hemodialysis: twice a week, or once weekly hemodialysis combined with low-protein low-phosphorus diet?]. AB - The start of dialysis treatment is a critical step in the care management of chronic renal failure patients. When hemodialysis is performed three times a week, rapid loss of kidney function and of urine volume output generally occur and this represents an unfavorable prognostic factor. Instead, reducing frequency of hemodialysis sessions, as well as peritoneal dialysis, can contribute to a lesser decrease of residual renal function. Unfortunately, the existing protocols for an incremental hemodialysis approach are not particularly common and they are generally limited to a twice a week hemodialysis schedule. In addition to clinical and economic reasons, an incremental approach to ESRD also contributes to better social and psychological adaptation by the patients to the dramatic change in living conditions linked to the maintenance dialysis treatment. In patients who have attitude for low-protein nutritional therapy, a once weekly dialysis schedule combined with low-protein, low-phosphorus, normal to high energy diet in the remaining six days of the week can be implemented in selected patients. In our experience, this kind of program produced important clinical results and reduction in costs and hospitalization. When compared with a three times a week dialysis schedule, a greater protection of residual renal function and of urine volume output, lower increase in 2 microglobulin, better control of phosphorus and less consumption of phosphate binders and erythropoietin were observed. Careful clinical monitoring and nutrition is essential for the safety and optimization of infrequent hemodialysis. Long-term follow-up analysis shows favorable effects on the overall survival. Furthermore, twice a week hemodialysis is not the only option for an incremental approach of dialysis commencing. In patients who have a good attitude for low-protein nutritional therapy, its arrangement with a program of once weekly dialysis represents a real and effective alternative. PMID- 26845207 TI - [Management of antirheumatic drugs in kidney failure]. AB - The nephrologist deals with the management of patients with rheumatic disease, both diagnostically and therapeutically. He must determine whether the renal pathology is related to the rheumatologic disease, mostly through the use of the renal biopsy. In the second case, he must know the nephrotoxic potential of the drugs prescribed and adjust their use to the degree of renal impairment. This task is made difficult by the absence of controlled clinical trials regarding their use on patients with renal insufficiency or on chronic dialysis. For this reason, the prescription will have to take into account the pharmacokinetics of the drugs. Kidney failure can affect the metabolism of antirheumatic drugs determining their accumulation, which can lead to increased toxicity, either renal or systemic. On the other hand, dialysis can cause excessive drug removal, leading to sub-therapeutic pharmacological effects and to the need for additional doses. In this brief review, we will consider the nephrotoxic effects of some important drugs used in rheumatology and examined individually, with specific reference to rheumatoid arthritis: methotrexate, leflunamide, hydroxychloroquine, cyclosporine, biological DMARDs. In the past, therapeutic success in rheumatic diseases associated with kidney impairment was severely limited by the well- known nephrotoxicity of drugs such as gold salts, D-penicillamine, NSAIDs, COX-2 inhibitors. Although generally effective, they are contraindicated in case of kidney failure. Biologic therapies have recently opened new therapeutic perspectives. Nevertheless, it is worth stressing how our knowledge of their action is still incomplete and this may result in exposure to immune-mediated renal disease. PMID- 26845208 TI - [Technological advances and micro-inflammation in dialysis patients]. AB - As currently performed, on line hemodiafiltration reduces, but does not normalize, the micro-inflammation of uremic patients. Recent technological advances make it possible to further reduce the inflammation connected to the dialysis treatment. ?Short bacterial DNA fragments are pro-inflammatory and can be detected in the dialysis fluids. However, their determination is not currently within normal controls of the quality of the dialysate. The scenario may change once the analysis of these fragments yields reliable, inexpensive, quick and easy to evaluate the results. At variance with standard bicarbonate dialysate, Citrate dialysate induces far less inflammation both for the well-known anti-inflammatory effect of such buffer and also because it is completely acetate free, e.g. a definitely pro-inflammatory buffer. However, the extensive use of citrate dialysate in chronic dialysis is prevented because of concerns about its potential calcium lowering effect. In our view, high convective exchange on line hemodiafiltration performed with dialysate, whose sterility and a-pirogenicity is guaranteed by increasingly sophisticated controls and with citrate buffer whose safety is certified, can serve as the gold standard of dialysis treatments in future. PMID- 26845209 TI - [Use of rituximab in primary and secondary glomerulonephritis]. AB - Primary and secondary glomerulonephritis are a heterogeneous group of disorders characterized by "glomerular inflammation" with an immune-mediated pathogenesis. Considering the severe side effects of the immunosuppressive drugs, the therapeutic approach remains a challenge for the nephrologists. Corticosteroids, cytotoxic agents such as cyclophosphamide, or calcineurin inhibitors such as cyclosporine and tacrolimus, azathioprine and mycophenolate mofetil can all be used for the treatment of glomerulonephritis. Several studies has been published to better understand the pathogenesis of these diseases and to identify the drugs with lower toxicity. Different mechanisms involve, directly or indirectly, the B cells in the pathogenesis of glomerulonephritis. For this reason, the attention of the nephrologists has been focused on the identification of drugs that act at this level, such as chimeric monoclonal antibodies. Rituximab, binding to the CD20 receptor expressed on the surface of B cells, induces their apoptosis and persistent depletion for 6-9 months. B cells contribute to the immune response by the maturation into plasma cells with consequent antibody production, the processing and presentation of the antigen to T cells and the production of various cytokines. For these reasons, the potential role of these drugs in the treatment of primitives and secondary glomerulonephritis is clear. In this review, we aimed to evaluate the use of rituximab in the treatment of these diseases, by focusing on the results of the most recent clinical trials. PMID- 26845210 TI - [An unusual case of acute aminophylline intoxication]. AB - Theophylline/aminophylline use for asthma and chronic obstructive pulmonary disease has declined over time, as new and safer therapies developed. However, theophylline/aminophylline overdose can occur. Hereby it is described an unusual case of severe aminophylline intoxication due to mesodermic injections treated with CVVHDF session. PMID- 26845211 TI - [Candida peritonitis and sepsis due to Acinetobacter baumannii in peritoneal dialysis: an association with prognosis not always unfavourable]. AB - Fungal infections have a high incidence in patients receiving peritoneal dialysis. (1)?Peritoneal dialysis is often complicated by peritonitis which has only minimally mycotic etiology, but nonetheless it is associated with 15-45% mortality (8).? The opportunistic pathogens such as Candida can cause infection in immunocompromised conditions. Even the Acinetobacter tends to infect immunocompromised individuals and it has the same risk factors for infection as Candida: immunosuppression, malignancy, HIV positivity and all the other conditions of immunosuppression, central venous catheterization, mechanical ventilation and prolonged antibiotic therapy. The sepsis by Acinetobacter predicts a negative prognosis with the mortality rate between 20 to 60% (12), especially in cases of isolation of multi-resistant germs.? We present a case report of a CKD patient undergoing peritoneal dialysis therapy who was hospitalized for acute pancreatitis, later complicated by the development of pancreatic pseudocysts, C. albicans peritonitis with hematologic spread of the fungus, superimposed Acinetobacter baumannii sepsis and pneumonia. She has been subjected to percutaneous drainage of pseudocysts, to switch from peritoneal dialysis to hemodialysis, to various evacuative thoracentesis, and to polymicrobial therapy (meropenem, teicoplanina, tigeciclina, linezolid, colimicina, fluconazolo, etc.) that allowed the resolution of sepsis. The peculiarity of this case is represented by the numerous morbidity that the patient developed simultaneously, with the genesis of a complex clinical picture, by the combination of infections due to Candida albicans and Acinetobacter baumannii. Successful treatment strategies allowed to fight and cure a medical condition associated with a high mortality rate. PMID- 26845212 TI - [Membranous glomerulonephritis with crescent overlapping]. AB - Acute crescentic transformation is a rare but well described event in patients with membranous glomerulonephritis. We report our experience with a 66-year-old Caucasian man presented for rapid decline in renal function. For nearly 10 years, he was suffering from hypertension and mixed sensori-motor polyneuropathy. He performed therapy with prednisone and azathioprine, suspended 1 year before presentation. Moreover, six months before presentation, laboratory tests showed a serum creatinine concentration 220 mol/L and a 24-h protein excretion 0,75 g/d. The physical examination showed oedema and severe hypertension; the 24-h protein excretion was 1,1 gr/d and creatinine concentration was 550.8 mol/L; ANCA and other immunological tests were negative. There was no evidence of SLE, infection or malignancy. The kidney biopsy highlighted a membranous GN with crescentic overlap. The patient was treated with steroid and cyclophosphamide. Because there was no sign of improvement after 2 months, we stopped the cyclophosphamide therapy and the patient started chronic haemodialysis treatment. Unlike membranous nephropathy, patients with superimposed crescentic glomerulonephritis appear to have a more aggressive clinical course. The importance of recognizing this group of patients with membranous nephropathy and crescentic glomerulonephritis is that immunosuppressive therapy may ameliorate the progression of renal damage and in some cases early treatment was associated with useful recovery of renal function. PMID- 26845213 TI - [Cardiovascular Disease In Children With Ckd]. AB - Cardiovascular disease (CVD) is the most important risk factor for morbidity and mortality in patients with chronic kidney disease (CKD). Aim of this study was to evaluate cardiac and vascular geometry in children with CKD stages 2, 3 and 4.Twenty-seven patients (18 males and 9 females) mean age 10.9 +/- 5.4 years with CKD and 30 children (control group) were enrolled with comparable age and sex. Weight, height, systolic and diastolic blood pressure were evaluated. We also analyzed biochemical assessments and proteinuria. We performed echocardiography with Philips iE33 and pulse wave velocity (PWV) with Vicorder PWS system. We documented significantly higher level of left ventricular mass index (LVMI) (30.3 +/- 7.6 g/m2.7) and PWV (4.7 +/- 1.6 m/sec) in CKD patients. Left ventricular hypertrophy (LVH) was present in 12 % and concentric remodelling in 36% of our patients. PWV values were significantly correlated with interventricular septal thickness (p<0.01) and with LVMI (p<0.05). In this study we documented the alterations of cardiac and vascular geometry since the early stages of CKD. PWV and echocardiographic measurements must be considered to assess cardiovascular risk in children with CKD stages 2-4. PMID- 26845214 TI - Nephroprotection with saxagliptin. AB - The nephroprotective effect of the new anti-diabetic drugs acting on incretin system is suggested by preclinical studies. However, no study evaluating kidney effects of these drugs as primary outcome on the long term has been conducted in patients followed in diabetes centers. We designed a pilot observational study involving two diabetes clinics to evaluate the effect of prolonged treatment with saxagliptin on renal function in type 2 diabetics. Patients were enrolled if treated for at least 12 months with saxagliptin without concurrent changes to anti-hypertensive and lipid-lowering therapy. Primary outcome was to evaluate the effect of saxagliptin on albuminuria and estimated glomerular filtration rate (eGFR). Secondary outcomes were the effects of treatment on common clinical and laboratory parameters. Sixty-three patients were enrolled. After 12 months of treatment with saxagliptin, albuminuria declined from a mean (95%CI) of 39 (25 52) to 22 (14-30) mg/l (P<0.001), and the prevalence of increased albuminuria (>20 mg/L) diminished by 27% versus baseline. The anti-albuminuric effect was independent of glycemic and blood pressure control. The eGFR remained unchanged after treatment in the presence of decreased glycated hemoglobin (from 7.1 to 6.7%). Therefore, this pilot study suggests that saxagliptin treatment in diabetic patients at high renal risk is associated with a reduction in albuminuria and GFR stability. Prospective trials are required to confirm the potential nephroprotective effects of saxagliptin. PMID- 26845215 TI - [Epilepsy, vertigo, dizziness, headache, emesis as neurological manifestation in a Giteleman's Sindrome case]. AB - We report the case of a woman presenting the recent onset of multiple seizure and epilepsy episodes combined with other neurological symptoms (e.g. vertigo, dizziness, vomiting, headache). She was resistant to antiepileptic and symptomatic therapy, having been first admitted to the neurology ward and subsequently to the general medicine ward. In this case, several patient assessments and imaging exams were not conclusive evidence of specific etiopathogenesis, or definitive neurological illness; however, the patient showed laboratory indexes compatible with Gitelmans Syndrome. The correction of the electrolytic imbalances of tubulopathy (including low magnesium and potassium levels) led to the progressive improvement of clinical manifestations and the eventual interruption of the antiepileptic therapy. PMID- 26845216 TI - Effect of a magnetic field on the adsorptive removal of methylene blue onto wheat straw biochar. AB - Biochar pyrolyzed from wheat straw was innovatively used for the adsorptive removal of cationic dye methylene blue through exposure to a magnetic field. The adsorption capability of the biochar pyrolyzed at 200 degrees C exceeded that of samples pyrolyzed at higher temperatures. The surface acidic functional groups of wheat straw biochar were deduced to be more sensitive to the effects of the external magnetic field. The enhancement of the magnetic field achieved by increases in the initial dye concentration, and a decrease in the biochar dosage and solution pH, were more significant compared with those caused by other conditions. Kinetic experiments indicated that chemisorption occurred during adsorption. The qmax values for dye adsorption without, and with, an external magnetic field were found to be 46.6 and 62.5mg/g, respectively. These demonstrated that wheat straw biochar could be used for the efficient adsorption of pollutants when assisted by an external magnetic field. PMID- 26845218 TI - Efficient removal of zinc by multi-stress-tolerant yeast Pichia kudriavzevii A16. AB - Heavy metal bioaccumulation by growing microorganisms is a potential technique for treating the heavy metal pollution in food materials, e.g. fishery processing wastes. In this study, a multi-stress-tolerant yeast with high Zn tolerance and efficient Zn removal ability was screened and renamed as Pichia kudriavzevii A16 after identification. High salinity and low pH obviously increased the Zn bioaccumulation capacity of P. kudriavzevii A16, contributing to the increasing Zn removal rate of P. kudriavzevii A16 at 0.5 mmol/L Zn from 67.69% to 77.03% and 96.09%, respectively. P. kudriavzevii A16 displayed high specificity of Zn removal at high concentrations of Cu, while high concentrations of Cd significantly inhibited the Zn removal by restraining the yeast growth. P. kudriavzevii A16 possessed more powerful Zn removal ability than Saccharomyces cerevisiae CICC1211 under various environmental stresses. The multi-stress tolerant P. kudriavzevii A16 can be developed into a potential Zn removal agent using in complex food environments. PMID- 26845217 TI - Potential application of Alcaligenes faecalis strain No. 4 in mitigating ammonia emissions from dairy wastewater. AB - This research examined the potential mitigation of NH3 emissions from dairy manure via an enhanced aerobic bio-treatment with bacterium Alcaligenes faecalis strain No. 4. The studies were conducted in aerated batch reactors using air and pure oxygen. Aeration with air and oxygen removed approximately 40% and 100% total ammoniacal nitrogen (TAN), respectively. Intermittent oxygenation (every 2 or 4 h) reduced oxygen consumption by 95%, while attaining nearly identical TAN removal to continuous aeration. The results revealed that adequate oxygen supply and supplementing dairy wastewater with carbon are essential for this bioprocess. Based on the nitrogen mass balance, only 4% of TAN was released as NH3 gas, while the majority was retained in either the microbial biomass (58%) or converted to nitrogen gas (36%). The mass balance results reveal high potential for environmentally friendly bio-treatment of dairy wastewater using A. faecalis strain No. 4 with respect to NH3 emissions. PMID- 26845219 TI - Low pressure steam expansion pretreatment as a competitive approach to improve diosgenin yield and the production of fermentable sugar from Dioscorea zingiberensis C.H. Wright. AB - Development of efficient pretreatment methods which can disrupt the peripheral lignocellulose and even the parenchyma cells is of great importance for production of diosgenin from turmeric rhizomes. It was found that low pressure steam expansion pretreatment (LSEP) could improve the diosgenin yield by more than 40% compared with the case without pretreatment, while simultaneously increasing the production of fermentable sugar by 27.37%. Furthermore, little inhibitory compounds were produced in LSEP process which was extremely favorable for the subsequent biotransformation of fermentable sugar to other valuable products such as ethanol. Preliminary study showed that the ethanol yield when using the fermentable sugar as carbon source was comparable to that using glucose. The liquid residue of LSEP treated turmeric tuber after diosgenin production can be utilized as a quality fermentable carbon source. Therefore, LSEP has great potential in industrial application in diosgenin clean production and comprehensive utilization of turmeric tuber. PMID- 26845220 TI - Effects of aluminum chloride-catalyzed hydrothermal pretreatment on the structural characteristics of lignin and enzymatic hydrolysis. AB - In this study, Eucalyptus camaldulensis was pretreated with 0.02 M aluminum chloride (AlCl3) at 140-180 degrees C to obtain digestible substrates for glucose and lignin. The effects of AlCl3-catalyzed hydrothermal pretreatment on the degradation of carbohydrates, structural changes of lignin, crystallinity, morphologic changes, and cellulose conversion of the pretreated biomass have been investigated by HAPEC, HPLC, FT-IR, XRD, CP/MAS NMR, SEM, and 2D-HSQC NMR. Results showed that the pretreatment significantly removed hemicelluloses and cleaved beta-O-4 linkages of lignin at high temperatures. Under an optimum condition (at 170 degrees C for 1 h), almost all of hemicelluloses were removed and most of beta-O-4 linkages in lignin were cleaved, and 77.8% cellulose conversion of the pretreated biomass was achieved, which was 7.3-fold higher than that of the original biomass. In short, this process was regarded as a promising approach to achieve an efficient conversion of lignocellulosic biomass to fermentable glucose and residual lignin. PMID- 26845222 TI - Cardiopulmonary Exercise Testing in Systemic Sclerosis: 'Ars longa, vita brevis'. PMID- 26845221 TI - Clinical Significance of Viral Genome Persistence in the Myocardium of Patients with Dilated Cardiomyopathy. AB - BACKGROUND: The impact of myocardial viral persistence on the clinical outcome of patients with dilated cardiomyopathy (DCM) is still open to question. METHODS: Fifty-two patients with DCM were enrolled and followed for a median of 3.8 years with respect to death or heart transplantation. Studied patients were clinically stable for at least 6 months before hospitalization. They underwent coronary angiography and endomyocardial biopsy. Specimens were examined by histo- and immunohistochemistry, and the viral genomes of parvovirus B19, cytomegalovirus (CMV), Coxsackie B virus (CVB), and hepatitis B and C viruses were studied by real-time polymerase chain reaction. RESULTS: Forty-two out of 52 patients were available for clinical follow-up. The viral genome was detected in the myocardium of 32 out of 42 patients. Among the viruses studied, CMV and CVB were the most frequently found. Nine out of 42 patients achieved the predefined study end point. No statistically significant correlation was found between the presence of a persistent viral genome and study end point. No statistically significant relationship between viral genomes studied and immunohistology results was detected. CONCLUSIONS: High prevalence of a viral genome in the myocardium of patients with DCM did not have an influence on their long-term clinical outcome. PMID- 26845223 TI - Determining appropriate screening tools and cut-points for cognitive impairment in an elderly Chinese sample. AB - The establishment of normative data and screening cut-points for cognitive tasks is important to ensure the effective and timely detection of mild cognitive impairment (MCI) and Alzheimer's disease (AD). These need to be culturally relevant and account for known factors that impact on cognition such as age, education, and gender. In this study, 1,068 elderly Chinese residents of Shanghai completed a comprehensive series of cognitive tasks as part of a community screening study with 1027 meeting criteria for analysis, age M(SD) = 72.54 (8.40). MCI was detected in 267 individuals, AD in 50, and 710 had normal cognition. Receiver Operator Characteristic curve analysis indicated that the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) best differentiated normal cognition from MCI and AD. We present suggested cut points to differentiate between normal cognition and MCI and AD for the total sample, and when split according to education levels, age, and gender. Trends suggest that the MoCA was better suited to detecting MCI, and the MMSE was better for detecting AD. For younger and more educated participants, only a slight impairment was necessary to meet screening criteria, while a larger impairment was necessary for older and less educated participants. Both tasks had a high negative predictive values for MCI and AD, and variable positive predictive values. The cut-points presented can be used to inform future work using the MMSE and MoCA to screen for MCI and AD in older Chinese people. (PsycINFO Database Record PMID- 26845224 TI - The Reinforcement Sensitivity Theory of Personality Questionnaire (RST-PQ): Development and validation. AB - We report the development and validation of a questionnaire measure of the revised reinforcement sensitivity theory (rRST) of personality. Starting with qualitative responses to defensive and approach scenarios modeled on typical rodent ethoexperimental situations, exploratory and confirmatory factor analyses (CFAs) revealed a robust 6-factor structure: 2 unitary defensive factors, fight flight-freeze system (FFFS; related to fear) and the behavioral inhibition system (BIS; related to anxiety); and 4 behavioral approach system (BAS) factors (Reward Interest, Goal-Drive Persistence, Reward Reactivity, and Impulsivity). Theoretically motivated thematic facets were employed to sample the breadth of defensive space, comprising FFFS (Flight, Freeze, and Active Avoidance) and BIS (Motor Planning Interruption, Worry, Obsessive Thoughts, and Behavioral Disengagement). Based on theoretical considerations, and statistically confirmed, a separate scale for Defensive Fight was developed. Validation evidence for the 6 factor structure came from convergent and discriminant validity shown by correlations with existing personality scales. We offer the Reinforcement Sensitivity Theory of Personality Questionnaire to facilitate future research specifically on rRST and, more broadly, on approach-avoidance theories of personality. (PsycINFO Database Record PMID- 26845225 TI - Does the self-report Inventory of Callous-Unemotional Traits predict recidivism? AB - Callous-unemotional (CU) traits, that is, a lack of guilt or empathy and poverty of emotion, are believed to be the developmental precursor to psychopathy in adulthood, capturing its emotional detachment dimension. Similar to psychopathic adults, research shows that children and adolescents with high CU traits represent an important population at heightened risk for criminal behavior. The present study is the first to examine whether a self-report measure of CU traits, the Inventory of Callous-Unemotional Traits (ICU), predicts general and violent recidivism postinstitutional release among a sample of 227 juvenile justice involved adolescent boys (M age = 15.73, SD = 1.27). Results indicated that boys high on CU traits were faster to reoffend postrelease both nonviolently (Hazard Ratio [HR] = 1.27, p < .01) and violently (HR = 1.54, p < .05). Further, the Uncaring subscale of the ICU predicted faster time to general recidivism (HR = 1.21, p < .05), whereas the Callousness subscale (i.e., "I do not care who I hurt to get what I want") predicted faster time to violent recidivism (HR = 1.39, p < .05). The present study provides preliminary support for the predictive validity of a brief, yet comprehensive self-report measure of CU traits. Findings inform youth risk assessment by offering possibilities within the domain of self-report for screening high-risk youth in need of intensive, comprehensive, and individualized intervention. (PsycINFO Database Record PMID- 26845226 TI - Correction: "Childhood intussusception: 17-year experience at a tertiary referral centre in Hong Kong. AB - [This corrects the article DOI: 10.12809/hkmj144456]. PMID- 26845227 TI - A rare case of familial multiple subcutaneous lipomatosis with novel PALB2 mutation and increased predilection to cancers. AB - We describe the association of familial multiple subcutaneous lipomatosis with a PALB2 gene mutation (c.2716delT) and its increased predilection to cancers. PMID- 26845228 TI - Reproductive and oncologic outcome following robot-assisted laparoscopic radical trachelectomy for early stage cervical cancer. AB - OBJECTIVE: To investigate the reproductive and oncologic outcome following robotic radical trachelectomy for early stage cervical cancer. METHODS: All women with early stage cervical cancer planned for fertility-sparing robotic trachelectomy between December 2007 and April 2015 at two tertiary referral centers in Sweden were identified. Perioperative- and follow-up data was retrieved from prospective databases used for all robotic procedures at the respective institution and an additional review of computerized patient files was performed. Reproductive outcome evaluation was restricted to women with >=12months follow-up and an active wish to conceive. Oncological outcome was evaluated for all patients. RESULTS: Fifty-six women (3 stage IA1, 14 stage IA2 and 39 stage IB1) were included. The median age was 29years (range 23-41). Median follow-up was 24months (range 1-89). Seven trachelectomies were aborted in favor of a radical hysterectomy and/or chemoradiation due to nodal metastases or insufficient margins; two distant recurrences occurred in these women. A local recurrence was seen in two of the 49 women (4%) in whom the procedure was completed as planned. Seventeen of the 21 women (81%) in the reproductive follow up group conceived - 16 naturally and one following IVF. Sixteen women (94%) delivered in the third trimester, 12 women (71%) in gestational week >=36. One (6%) second trimester delivery occurred. CONCLUSION: The high fertility rate, low rate of premature deliveries and an acceptable rate of recurrence support the feasibility of robotic fertility-sparing radical trachelectomy in women with early stage cervical cancer. PMID- 26845229 TI - Distribution and characteristics of slow-cycling cells in rat vocal folds. AB - OBJECTIVES/HYPOTHESIS: Stem cells are known to proliferate at a slow rate in adult organs, and thus slow-cycling cells exhibiting pluripotency are considered tissue-specific stem cells in some organs. Slow-cycling cells in the vocal fold (VF) have not been well documented. Here we sought to clarify the distributions and characteristics of slow-cycling cells in rat VFs. METHODS: We applied double labeling technique to detect the distribution of slow-cycling cells. We injected the exogenous proliferation marker 5-bromo-2'-deoxyuridine (BrdU) into Sprague Dawley rats. After a chasing period, VFs were immunostained with antibodies to BrdU and the second endogenous proliferation marker, Ki-67. BrdU (+) Ki-67(+) cells were regarded as slow-cycling cells and counted by VF regions. To reveal slow-cycling cells' characteristic, their immunophenotypes were histologically investigated and their kinetics in injured VFs were evaluated. RESULTS: Most slow cycling cells were detected in the basal layer of the epithelium. Slow-cycling cells in the epithelium displayed a low positive ratio of E-cadherin and CK5 and a high positive ratio of vimentin and CD31 as compared with the other epithelial cells. The expression of S100A4 was low in slow-cycling cells of the lamina propria and the macula flava. FGFR1, HAS1, HAS2, and HAS3 were not detected in the slow-cycling cells. A time-dependent reduction of slow-cycling cells was observed in injured VFs. CONCLUSION: Most slow-cycling cells resided in the epithelium, exhibiting various phenotypes in a relatively undifferentiated condition, and they are suspected to contribute to the tissue repair of the injured VFs. LEVEL OF EVIDENCE: N/A. PMID- 26845231 TI - Total Synthesis of (+/-)-Strictamine. AB - The total synthesis of strictamine has been achieved in nine steps from a known enol triflate. Characteristic features of our approach included: a) creation of a C7 all-carbon quaternary stereocenter at an early synthetic stage; b) use of an N,N-dimethyl tertiary amine as a surrogate of the primary amine for the rapid build-up of a functionalized 2-azabicyclo[3,3,1]nonan-9-one skeleton (achieved by using a reaction sequence of alpha-bromination of the ketone, followed by a stereoconvergent intramolecular nucleophilic substitution reaction); and c) a late-stage construction of the indolenine unit. PMID- 26845232 TI - Shear dispersion in a capillary tube with a porous wall. AB - An analytical expression is presented for the shear dispersion during solute transport in a coupled system comprised of a capillary tube and a porous medium. The dispersion coefficient is derived in a capillary tube with a porous wall by considering an accurate boundary condition, which is the continuity of concentration and mass flux, at the interface between the capillary tube and porous medium. A comparison of the obtained results with that in a non-coupled system identifies three regimes including: diffusion-dominated, transition, and advection-dominated. The results reveal that it is essential to include the exchange of solute between the capillary tube and porous medium in development of the shear dispersion coefficient for the last two regimes. The resulting equivalent transport equation revealed that due to mass transfer between the capillary tube and the porous medium, the dispersion coefficient is decreased while the effective velocity in the capillary tube increases. However, a larger effective advection term leads to faster breakthrough of a solute and enhances mass delivery to the porous medium as compared with the classical double-porosity model with a non-coupled dispersion coefficient. The obtained results also indicate that the finite porous medium gives faster breakthrough of a solute as compared with the infinite one. These results find applications in solute transport in porous capillaries and membranes. PMID- 26845230 TI - Oncogene swap as a novel mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor in lung cancer. AB - Mutant selective epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as rociletinib and AZD9291, are effective for tumors with T790M secondary mutation that become refractory to first-generation EGFR-TKI. However, acquired resistance to these prospective drugs is anticipated considering the high adaptability of cancer cells and the mechanisms remain largely obscure. Here, CNX-2006 (tool compound of rociletinib) resistant sublines were established by chronic exposure of HCC827EPR cells harboring exon 19 deletion and T790M to CNX-2006. Through the analyses of these resistant subclones, we identified two resistant mechanisms accompanied by MET amplification. One was bypass signaling by MET amplification in addition to T790M, which was inhibited by the combination of CNX-2006 and MET-TKI. Another was loss of amplified EGFR mutant allele including T790M while acquiring MET amplification. Interestingly, MET-TKI alone was able to overcome this resistance, suggesting that oncogenic dependence completely shifted from EGFR to MET. We propose describing this phenomenon as an "oncogene swap." Furthermore, we analyzed multiple lesions from a patient who died of acquired resistance to gefitinib, then found a clinical example of an oncogene swap in which the EGFR mutation was lost and a MET gene copy was gained. In conclusion, an "oncogene swap" from EGFR to MET is a novel resistant mechanism to the EGFR-TKI. This novel mechanism should be considered in order to avoid futile inhibition of the original oncogene. PMID- 26845233 TI - Fe(0) Nanomotors in Ton Quantities (10(20) Units) for Environmental Remediation. AB - Despite demonstrating potential for environmental remediation and biomedical applications, the practical environmental applications of autonomous self propelled micro-/nanorobots have been limited by the inability to fabricate these devices in large (kilograms/tons) quantities. In view of the demand for large scale environmental remediation by micro-/nanomotors, which are easily synthesized and powered by nontoxic fuel, we have developed bubble-propelled Fe(0) Janus nanomotors by a facile thermally induced solid-state procedure and investigated their potential as decontamination agents of pollutants. These Fe(0) Janus nanomotors, stabilized by an ultrathin iron oxide shell, were fuelled by their decomposition in citric acid, leading to the asymmetric bubble propulsion. The degradation of azo-dyes was dramatically increased in the presence of moving self-propelled Fe(0) nanomotors, which acted as reducing agents. Such enhanced pollutant decomposition triggered by biocompatible Fe(0) (nanoscale zero-valent iron motors), which can be handled in the air and fabricated in ton quantities for low cost, will revolutionize the way that environmental remediation is carried out. PMID- 26845234 TI - Teaching at the Bedside. Maximal Impact in Minimal Time. AB - Academic physicians encounter many demands on their time including patient care, quality and performance requirements, research, and education. In an era when patient volume is prioritized and competition for research funding is intense, there is a risk that medical education will become marginalized. Bedside teaching, a responsibility of academic physicians regardless of professional track, is challenged in particular out of concern that it generates inefficiency, and distractions from direct patient care, and can distort physician-patient relationships. At the same time, the bedside is a powerful location for teaching as learners more easily engage with educational content when they can directly see its practical relevance for patient care. Also, bedside teaching enables patients and family members to engage directly in the educational process. Successful bedside teaching can be aided by consideration of four factors: climate, attention, reasoning, and evaluation. Creating a safe environment for learning and patient care is essential. We recommend that educators set expectations about use of medical jargon and engagement of the patient and family before they enter the patient room with trainees. Keep learners focused by asking relevant questions of all members of the team and by maintaining a collective leadership style. Assess and model clinical reasoning through a hypothesis-driven approach that explores the rationale for clinical decisions. Focused, specific, real-time feedback is essential for the learner to modify behaviors for future patient encounters. Together, these strategies may alleviate challenges associated with bedside teaching and ensure it remains a part of physician practice in academic medicine. PMID- 26845235 TI - Fragment Screening of Soluble Epoxide Hydrolase for Lead Generation-Structure Based Hit Evaluation and Chemistry Exploration. AB - Soluble epoxide hydrolase (sEH) is involved in the regulation of many biological processes by metabolizing the key bioactive lipid mediator, epoxyeicosatrienoic acids. For the development of sEH inhibitors with improved physicochemical properties, we performed both a fragment screening and a high-throughput screening aiming at an integrated hit evaluation and lead generation. Followed by a joint dose-response analysis to confirm the hits, the identified actives were then effectively triaged by a structure-based hit-classification approach to three prioritized series. Two distinct scaffolds were identified as tractable starting points for potential lead chemistry work. The oxoindoline series bind at the right-hand side of the active-site pocket with hydrogen bonds to the protein. The 2-phenylbenzimidazole-4-sulfonamide series bind at the central channel with significant induced fit, which has not been previously reported. On the basis of the encouraging initial results, we envision that a new lead series with improved properties could be generated if a vector is found that could merge the cyclohexyl functionality of the oxoindoline series with the trifluoromethyl moiety of the 2-phenylbenzimidazole-4-sulfonamide series. PMID- 26845237 TI - Corrigendum to "High-speed atomic force microscopy: Imaging and force spectroscopy" [FEBS Lett. 588 (19) (2014) 3631-3638]. PMID- 26845236 TI - Diffuse alveolar hemorrhage in IgA nephropathy: case series and systematic review of the literature. AB - OBJECTIVES: To describe the spectrum of pulmonary involvement in immunoglobulin A nephropathy (IgAN). METHODS: We describe two patients with pulmonary renal syndrome related to IgAN and a systematic review of previously reported cases of IgAN and lung involvement. RESULTS: We identified 23 reports of IgAN-related pulmonary disease, including 19 reports of alveolar hemorrhage and two cases of organizing pneumonia. Dyspnea (84%), hemoptysis (74%), cough (53%) and fever (47%) were common presenting complaints. Simultaneous involvement of kidneys and lung was the most common presentation (42%) but alveolar hemorrhage occurred independent of renal disease in one-fifth (21%). Azotemia was seen in 55.5% at presentation. Mesangio-proliferative glomerulonephritis was the most common biopsy finding and crescentic glomerulonephritis was seen in 27.7%. Among patients undergoing lung biopsy, capillaritis was seen in 72.7%; 37.5% of these had IgA deposits. Steroids with cyclophosphamide, followed by maintenance with methotrexate or azathioprine was used in 44%. Mechanical ventilation, dialysis and plasmapheresis were other adjunctive therapies used. IgAN-related alveolar hemorrhage was associated with a mortality of 26.3% and significant morbidity, with 52.7% having end-stage kidney disease despite immunosuppression. Organizing pneumonia with pulmonary IgA deposition is a well-described association of IgAN. CONCLUSION: These findings are similar to our previous observations of Henoch Schonlein purpura (HSP)-related alveolar hemorrhage, highlighting the similarities of these related syndromes. Multicentric studies of IgAN and HSP related pulmonary renal syndrome with a standard protocol are needed to define their similarities and differences, optimum suppression and its role in preventing renal progression in this setting. PMID- 26845239 TI - The Dimerization of H2NO. AB - H2NO is the prototype of aminoxyls, kinetically persistent free radicals. The potential dimerization and reaction modes of H2NO are examined. The dimer potential energy surface features a barely metastable O-O bound species and several locally bound dimeric structures. One of these, a rectangular or rhomboid O-N-O-N ring, is a characteristic structural feature of more stable aminoxyls in the solid state. Its electronic structure is related to other four-center six electron systems. A general picture of the weak dimer binding is constructed for these and other H2NO dimers from a balance of four-electron repulsions between NO pi electrons, and two-electron attractive interaction between the singly occupied pi* orbitals of the diradical. The most stable diradical structure is a surprisingly strongly hydrogen bonded dimer diradical. The barriers separating the other isomers from this global minimum are calculated to be small. PMID- 26845240 TI - Observation of potentially troublesome (2) JCC correlations in 1,1-ADEQUATE spectra. AB - Despite the tremendous usage of HMBC to establish long-range (1) H-(13) C and (1) H-(15) N heteronuclear correlations, an inherent drawback of the experiment is the indeterminate nature of the (n) JXH correlations afforded by the experiment. A priori there is no reliable way of determining whether a given (n) JCH correlation is, for example, via two-, three-, or sometimes even four-bonds. This limitation of the HMBC experiment spurred the development of the ADEQUATE family of NMR experiments that rely on, in the case of 1,1-ADEQUATE, an out-and-back transfer of magnetization via the (1) JCC homonuclear coupling constant, which is significantly larger than (n) JCC (where n = 2-4) couplings in most cases. Hence, the 1,1-ADEQUATE experiment has generally been assumed to unequivocally provide the equivalent of (2) JCH correlations. The recent development of the 1,1- and 1,n-HD-ADEQUATE experiments that can provide homodecoupling for certain (1) JCC and (n) JCC correlations has increased the sensitivity of the ADEQUATE experiments significantly and can allow acquisition of these data in a fraction of the time required for the original iterations of this pulse sequence. With these gains in sensitivity, however, there occasionally come unanticipated consequences. We have observed that the collapse of proton multiplets, in addition to providing better s/n for the desired (1) JCC correlations can facilitate the observation of typically weaker (2) JCC correlations across intervening carbonyl resonances in 1,1-HD-ADEQUATE spectra. Several examples are shown, with the results supported by the measurement of the (2) JCC coupling constants in question using J-modulated-HD-ADEQUATE and DFT calculations. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26845241 TI - Fibronectin assembly during early embryo development: A versatile communication system between cells and tissues. AB - BACKGROUND: Fibronectin extracellular matrix is essential for embryogenesis. Its assembly is a cell-mediated process where secreted fibronectin dimers bind to integrin receptors on receiving cells, which actively assemble fibronectin into a fibrillar matrix. During development, paracrine communication between tissues is crucial for coordinating morphogenesis, typically being mediated by growth factors and their receptors. Recent reports of situations where fibronectin is produced by one tissue and assembled by another, with implications on tissue morphogenesis, suggest that fibronectin assembly may also be a paracrine communication event in certain contexts. RESULTS: Here we addressed which tissues express fibronectin (Fn1) while also localizing assembled fibronectin matrix and determining the mRNA expression and/or protein distribution pattern of integrins alpha5 and alphaV, alpha chains of the major fibronectin assembly receptors, during early chick and mouse development. We found evidence supporting a paracrine system in fibronectin matrix assembly in several tissues, including immature mesenchymal tissues, components of central and peripheral nervous system and developing muscle. CONCLUSIONS: Thus, similarly to growth factor signaling, fibronectin matrix assembly during early development can be both autocrine and paracrine. We therefore propose that it be considered a cell-cell communication event at the same level and significance as growth factor signaling during embryogenesis. PMID- 26845242 TI - Isotretinoin treatment reduces acne lesions but not directly lesional acne inflammation. PMID- 26845244 TI - The Role of Surface Nanotopography and Chemistry on Primary Neutrophil and Macrophage Cellular Responses. AB - Synthetic materials employed for enhancing, replacing, or restoring biological functionality may be compromised by the host immune responses that they evoke. Surface modification has attracted substantial attention as a tool to modulate the host response to synthetic materials; however, how surface nanotopography combined with chemistry affects immune effector cell responses is still poorly understood. To address this open question, a unique set of model surfaces with controlled surface nanotopography in the range of 16, 38, and 68 nm has been generated. Tailored outermost surface chemistry that was amine, carboxyl, or methyl group rich has been provided. The combinations of these properties yield 12 surface types that are subject to functional assays assessing key immune effector cells, namely, primary neutrophil and macrophage responses in vitro. The data demonstrate that surface nanotopography leads to enhanced matrix metalloproteinase-9 production from primary neutrophils, and a decrease in pro inflammatory cytokine secretion from primary macrophages. Together, these results are the first to directly compare the immunomodulatory effects of the cooperative interplay between surface nanotopography and chemistry. PMID- 26845245 TI - Surface bound VEGF mimicking peptide maintains endothelial cell proliferation in the absence of soluble VEGF in vitro. AB - Continuous glucose monitoring is an efficient method for the management of diabetes and in limiting the complications induced by large fluctuations in glucose levels. For this, intravascular systems may assist in producing more reliable and accurate devices. However, neovascularization is a key factor to be addressed in improving their biocompatibility. In this scope, the perennial modification of the surface of an implant with the proangiogenic Vascular Endothelial Growth Factor mimic peptide (SVVYGLR peptide sequence) holds great promise. Herein, we report on the preparation of gold substrates presenting the covalently grafted SVVYGLR peptide sequence and their effect on HUVEC behavior. Effective coupling was demonstrated using XPS and PM-IRRAS. The produced surfaces were shown to be beneficial for HUVEC adhesion. Importantly, surface bound SVVYGLR is able to maintain HUVEC proliferation even in the absence of soluble VEGF. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1425 1436, 2016. PMID- 26845247 TI - Effect of Conjugation on Electron Distributions. Separation of sigma and pi Terms. AB - The ground states of unsaturated molecules with C(s) symmetry have separate sigma and pi molecular orbitals. This makes it possible to separately calculate the sigma and pi Hirshfeld populations and to analyze the effect of structural changes in more detail. A number of types of compounds have been studied: vinyl derivatives, 1-substituted hexatrienes, phenyl derivatives, and six-membered ring heterocycles. The results are shown as plots of changes in population vs atoms. The sigma and pi components vary widely, depending on pi conjugation, sigma inductive effects, and sigma/pi polarization. When an electron withdrawing group is attached to an alkene carbon, significant sigma density is transferred to it, and to compensate pi density is transferred to the substituent. Such interactions are similar to those found when a carbonyl or other ligands are attached to a metal. PMID- 26845246 TI - Diffusion-Weighted Magnetic Resonance Imaging for Therapy Response Monitoring and Early Treatment Prediction of Photothermal Therapy. AB - Photothermal therapy (PTT) as a relatively new cancer treatment method has attracted worldwide attention. Previous research on PTT has focused on its therapy efficiency and selectivity. The early prognosis of PTT, which is pivotal for the assessment of the treatment and the therapy stratification, however, has been rarely studied. In the present study, we investigated diffusion-weighted magnetic resonance imaging (DW-MRI) as a tool for therapy monitoring and early prognosis of PTT. To this end, we injected PEGylated graphene oxide (GO-PEG) or iron oxide deposited graphene oxide (GO-IONP-PEG) to 4T1 tumor models and irradiated the tumors at different drug-light intervals to induce PTT. For GO IONP-PEG injected animals, we also included therapy arms where an external magnetic field was applied to the tumors to improve the delivery of the nanoparticle transducers. DW-MRI was performed at different time points after PTT and the tumor apparent diffusion coefficients (ADCs) were analyzed and compared. Our studies show that photothermal agents, magnetic guidance, and drug-light intervals can all affect PTT treatment efficacy. Impressively, ADC value changes at early time points after PTT (less than 48 h) were found to be well-correlated with tumor growth suppression that was apparent days or weeks later. The changes were most sensitive to conditions that can extend the survival for more than 4 weeks, in which cases the 48 h ADC values were increased by more than 80%. These studies demonstrate for the first time that DW-MRI can be an accurate prognosis tool for PTT, suggesting an important role it can play in the future PTT evaluation and clinical translation of the modality. PMID- 26845248 TI - Role of alpha1D -adrenoceptors in vascular wall hypertrophy during angiotensin II induced hypertension. AB - The in vivo effect of continuous angiotensin II (Ang II) infusion on arterial blood pressure, vascular hypertrophy and alpha1 -adrenoceptors (alpha1 -ARs) expression was explored. Alzet((r)) minipumps filled with Ang II (200 ng kg(-1) min(-1) ) were subcutaneously implanted in male Wistar rats (3 months-old). Groups of rats were also treated with losartan, an AT1 R antagonist, or with BMY 7378, a selective alpha1D -AR antagonist. Blood pressure was measured by tail cuff; after 2 or 4 weeks of treatment, vessels were isolated for functional and structural analyses. Angiotensin II increased systolic blood pressure. Phenylephrine-induced contraction in aorta was greater (40% higher) in Ang II treated rats than in the controls, and similar effect occurred with KCl 80 mm. Responses in tail arteries were not significantly different among the different groups. Angiotensin II decreased alpha1D -ARs without modifying the other alpha1 ARs and induced an increase in media thickness (hypertrophy) in aorta, while no structural change occurred in tail artery. Losartan prevented and reversed hypertension and hypertrophy, while BMY 7378 prevented and reversed the aorta's hypertrophic response, without preventing or reversing hypertension. Findings indicate that Ang II-induced aortic hypertrophic response involves Ang II-AT1 Rs and alpha1D -ARs. Angiotensin II-induced alpha1D -AR-mediated vascular remodeling occurs independently of hypertension. Findings identify a alpha1D -AR-mediated process whereby Ang II influences aortic hypertrophy independently of blood pressure elevation. PMID- 26845249 TI - Increased ratio of ICOS(+) /PD-1(+) follicular helper T cells positively correlates with the development of human idiopathic membranous nephropathy. AB - To identify the frequencies of different subsets of peripheral blood follicular helper T (Tfh) cells in human idiopathic membranous nephropathy (IMN), 39 patients with new onset IMN and 18 age- and gender-matched healthy controls (HC) were enrolled for this study. The frequency of Tfh cells in venous blood were measured by flow cytometry, while concentration of serum IL-21 was detected by enzyme-linked immunosorbent assay. Correlation between the clinical features of IMN and Tfh cells was assessed by Spearman's rank correlation test. Overall, the frequencies of total, ICOS(+) , and PD-1(+) Tfh cells were increased in IMN patients, while the ratio of ICOS(+) /PD-1(+) Tfh cells positively correlated with IMN progression. However, the elevated serum IL-21 level in three subgroups of IMN patients, stratified based on 24-h urine protein levels, was not statistically significant compared to HC. Nonetheless, intracellular IL-21 in Tfh cells was generally increased in all IMN patients, and closely correlated with IMN development. Finally, the frequency of IL-21(+) Tfh cells and the ratio of ICOS(+) /PD-1(+) Tfh cells were positively correlated with the estimated 24-h urine protein of IMN patients. The data indicated that Tfh cells contribute to the pathogenicity of IMN. The ratio of ICOS(+) /PD-1(+) Tfh cells and the frequency of IL-21(+) Tfh cells may be indicators for evaluating the IMN development. PMID- 26845250 TI - High-Throughput and Label-Free Blood-on-a-Chip for Malaria Diagnosis. AB - The malaria parasite Plasmodium falciparum (Pf) changes the structure and mechanical properties of red blood cells (RBCs). These changes decrease deformability and increase cytoadherence of Pf-infected RBCs to the vascular endothelium, eventually leading to flow occlusions in capillary vessels. In this study, to detect Pf-infected RBCs effectively, deformability and viscosity of blood sample are measured simultaneously and indirectly by quantifying blood flow in a microfluidic device. The microfluidic device is designed by mimicking a Wheatstone-bridge electric circuit. To measure RBC deformability, a deformability assessment chamber (DAC) at the left lower side channel has parallel microfluidic filters. After delivering blood sample and 1* PBS solution at the same flow rate, hemodynamic properties are measured using a time-resolved microparticle image velocimetry technique. Blood volume delivered into the DAC for 200 s is evaluated as a deformability index. Subsequently, blood viscosity is quantified by monitoring blood-filled width of parallel flows in the microfluidic device. The proposed method is applied to evaluate variations in biophysical properties of blood samples partially mixed with normal RBCs and hardened RBCs. As a result, RBC deformability is more effective than blood viscosity in the detection of blood samples with hardened RBC volume fraction of 5%. The microfluidic device is also applied to detect Pf-infected RBCs. When parasitemia is greater than 0.515% for ring stage, 0.0544% for trophozoite stage, and 0.0054% for schizont stage, the measured velocity fields show unstable behavior because of cytoadherence of Pf-infected RBCs. Blood volume delivered into the DAC significantly decreases with increasing parasitemia. The experimental method proposed in this study can detect Pf-infected RBCs with good accuracy. PMID- 26845251 TI - Indomethacin-Kollidon VA64 Extrudates: A Mechanistic Study of pH-Dependent Controlled Release. AB - Because of its weakly acidic nature (pKa of 4.5), indomethacin presents an aqueous solubility that significantly increases when changing from acidic to neutral/alkaline pH (1.5 MUg/mL at pH 1.2 and 105.2 MUg/mL at pH 7.4). We have therefore investigated the impact of the dissolution medium pH on the dissolution performance of indomethacin:Kollidon VA64 extrudates. The impact of the drug loading on the dissolution properties of these systems was also examined (5%, 15%, 30%, 50%, 70%, and 90% drug loading). Time-resolved Raman spectroscopy along with in-line UV-vis spectrophotometry was employed to directly relate changes in dissolution behavior to physicochemical changes that occur to the extrudate during the test. The dissolution tests were performed in pH 2 HCl (to mimic the stomach conditions), and this was then switched during the experiment to pH 6.8 phosphate buffer (to simulate the poststomach conditions). The rotating disc dissolution rate test was also used to simultaneously measure the dissolution rate of both the drug and the polymer. We found that in pH 2 HCl buffer, for the 15% or higher drug-loaded extrudates, Kollidon VA64 preferentially dissolves from the exterior of the compact leaving an amorphous drug-rich hydrophobic shell, which, similarly to an enteric coating, inhibits the drug release. The in situ formation of an enteric coating has been previously hypothesized, and this has been the first time that is directly observed in a pH-variable dissolution test. The dissolution medium switch to pH 6.8 phosphate buffer, due to the large increase of the aqueous solubility of indomethacin at this pH, leads to rapid dissolution of the material forming the coating and therefore total drug release. In contrast, the 5% extrudate is fully hydrated and quickly dissolves at low pH pointing to a dissolution performance dependent on highly water-soluble Kollidon VA64. PMID- 26845252 TI - Acute hepatitis E virus infection in human immunodeficiency virus-positive men and women in Nepal: Not quite a rare entity. PMID- 26845253 TI - Anomer-Specific Recognition and Dynamics in a Fucose-Binding Lectin. AB - Sugar binding by a cell surface ~29 kDa lectin (RSL) from the bacterium Ralstonia solanacearum was characterized by NMR spectroscopy. The complexes formed with four monosaccharides and four fucosides were studied. Complete resonance assignments and backbone dynamics were determined for RSL in the sugar-free form and when bound to l-fucose or d-mannose. RSL was found to interact with both the alpha- and the beta-anomer of l-fucose and the "fucose like" sugars d-arabinose and l-galactose. Peak splitting was observed for some resonances of the binding site residues. The assignment of the split signals to the alpha- or beta-anomer was confirmed by comparison with the spectra of RSL bound to methyl-alpha-l fucoside or methyl-beta-l-fucoside. The backbone dynamics of RSL were sensitive to the presence of ligand, with the protein adopting a more compact structure upon binding to l-fucose. Taking advantage of tryptophan residues in the binding sites, we show that the indole resonance is an excellent reporter on ligand binding. Each sugar resulted in a distinct signature of chemical shift perturbations, suggesting that tryptophan signals are a sufficient probe of sugar binding. PMID- 26845254 TI - Self-pathology, the five-factor model, and bloated specific factors: A cautionary tale. AB - The five-factor model (FFM) is widely regarded as a useful model for the structure of both normal and maladaptive personality traits. However, recent factor analytic studies have suggested that deficits in the sense of self fall outside the FFM. The current study replicates and extends these findings, illustrating that factors can be situated outside a higher-order domain by including a relatively large number of closely related scales, forming what is known as a bloated specific factor. A total of 1,553 participants (M age = 37.8 years, SD = 13.1) were recruited across 3 studies. One measure of self-pathology (including 15 scales) and 2 measures of the FFM were administered, along with 17 measures of anxiousness and 12 measures of social withdrawal/sociability. Across 2 independent samples and 2 different measures of the FFM, deficits in the sense of self separated from neuroticism when all 15 scales of self-pathology were included. However, self-pathology loaded with FFM neuroticism when only a subset of the self-pathology scales was included. This finding was replicated with measures of social withdrawal/sociability, although only partially replicated with measures of anxiousness. Implications of these findings for past and future factor analytic studies of the structure of psychopathology are discussed. PMID- 26845255 TI - Characterizing and predicting trajectories of disordered eating over adolescence. AB - This study sought to identify distinct trajectory classes of growth of disordered eating (DE), and their respective correlates and risk factors. Females ages 12-19 years (Australian Twin Registry) were interviewed by telephone with the Eating Disorder Examination on 3 occasions (Wave 1: N = 699; Wave 2: N = 669; Wave 3: N = 499). Each participant also completed self-report measures across all waves, and their parents at Waves 1 and 2. Growth mixture modeling determined the optimal classes representing DE growth trajectories over 3 data-points. The best fit was a 3-class solution constituting: (a) no growth in DE over time (90%; low static) where 10% reported a lifetime eating disorder (ED); (b) a high intercept but decreasing over time (7%; 53% had a lifetime ED; attenuating); (c) an increasing level of DE (3%; 80% experiencing a lifetime ED; escalating). The majority (64%) of EDs in the attenuating group were diagnosed at Wave 1, whereas 84% of EDs in the escalating group were diagnosed at subsequent waves. The low static group had fewest significant correlates/risk factors for DE. A multivariable GEE identified that over adolescence, internalization of the thin ideal was 2.5 times more likely characterize an escalating rather than low-static DE symptom trajectory. These findings underscore the fundamental importance of concentrating efforts on reducing the potency of the thin ideal message, and strategies directed toward resolving life stressors by effective management of emotion and problem resolution, in order to prevent the development of DE. PMID- 26845256 TI - The role of interpersonal conflict and perceived social support in nonsuicidal self-injury in daily life. AB - Although accumulating microlongitudinal research has examined emotion regulatory models of nonsuicidal self-injury (NSSI), few studies have examined how interpersonal contingencies influence daily NSSI behavior. Participants with repeated NSSI (N = 60) provided daily ratings of perceived social support, interpersonal conflict, and NSSI urges and behaviors for 14 days. Consistent with interpersonal models of NSSI, we hypothesized that participants would be more likely to engage in NSSI on days when they experienced high levels of interpersonal conflict, that NSSI acts that were revealed to others would be followed by desirable interpersonal changes (i.e., greater support, less conflict), and that these interpersonal changes would, in turn, predict stronger NSSI urges and more frequent NSSI behavior. Consistent with hypotheses, daily conflict was associated with stronger same-day NSSI urges and greater likelihood of NSSI acts. Perceived support increased following NSSI acts that had been revealed to others, but not unrevealed NSSI acts. This perceived support was, in turn, associated with a stronger NSSI urges and greater likelihood of engaging in NSSI on the following day. Moreover, participants whose NSSI was revealed to others engaged in more total NSSI acts during the diary period than those whose NSSI was not revealed to others. Inconsistent with hypotheses, interpersonal conflict did not decrease following NSSI, regardless of whether or not these acts were revealed to others. Together, these results provide preliminary support for interpersonal reinforcement models of NSSI and highlight the importance of expanding research in this area to include interpersonal contingencies that may influence this behavior. (PsycINFO Database Record PMID- 26845257 TI - Frontal-striatum dysfunction during reward processing: Relationships to amotivation in schizophrenia. AB - Schizophrenia is characterized by deficits of context processing, thought to be related to dorsolateral prefrontal cortex (DLPFC) impairment. Despite emerging evidence suggesting a crucial role of the DLPFC in integrating reward and goal information, we do not know whether individuals with schizophrenia can represent and integrate reward-related context information to modulate cognitive control. To address this question, 36 individuals with schizophrenia (n = 29) or schizoaffective disorder (n = 7) and 27 healthy controls performed a variant of a response conflict task (Padmala & Pessoa, 2011) during fMRI scanning, in both baseline and reward conditions, with monetary incentives on some reward trials. We used a mixed state-item design that allowed us to examine both sustained and transient reward effects on cognitive control. Different from predictions about impaired DLPFC function in schizophrenia, we found an intact pattern of increased sustained DLPFC activity during reward versus baseline blocks in individuals with schizophrenia at a group level but blunted sustained activations in the putamen. Contrary to our predictions, individuals with schizophrenia showed blunted cue related activations in several regions of the basal ganglia responding to reward predicting cues. Importantly, as predicted, individual differences in anhedonia/amotivation symptoms severity were significantly associated with reduced sustained DLPFC activation in the same region that showed overall increased activity as a function of reward. These results suggest that individual differences in motivational impairments in schizophrenia may be related to dysfunction of the DLPFC and striatum in motivationally salient situations. PMID- 26845258 TI - Course of depression in a 10-year prospective study: Evidence for qualitatively distinct subgroups. AB - The course of depressive disorders can vary considerable, with some individuals exhibiting a chronic course and poor outcomes, while others have a more episodic course and better outcomes. However, it is unclear whether degree of chronicity is continuous or reflects qualitatively distinct subgroups. Using data from a 5 wave, 10-year, naturalistic study of 127 depressed outpatients, we examined whether depression chronicity lies on a continuum or manifests natural boundaries. Spline regression was used to test 7 continuous and discontinuous models of the relationship between depression during the first follow-up interval and multiple outcomes at subsequent follow-ups. In order to further validate the findings, we also created empirically derived subgroups based on the results of the spline regression analyses and compared them on baseline clinical characteristics and long-term outcomes. There was a clear and consistent discontinuity indicating that for higher levels of chronicity during the first 30 month period, depression was linearly related to outcome; in contrast, for lower levels of chronicity, depression in the initial interval was unrelated to subsequent outcomes. The findings were strikingly consistent across the 4 follow up evaluations using multiple outcomes and goodness-of-fit indices. In addition, the chronic group--as defined by the first follow-up period--exhibited more baseline chronic depression, anxiety and personality disorders, family history of dysthymia, and childhood adversity, and was more likely to attempt suicide and be hospitalized during follow-up, than the nonchronic group. Results suggest that there are qualitatively distinct classes of patients with more and less chronic depressions, and support the utility of longitudinal course as a means of parsing depression into more homogeneous subgroups. PMID- 26845259 TI - Top-down attention and selection history in psychopathy: Evidence from a community sample. AB - Psychopathy is a severe personality disorder, the core of which pertains to callousness, an entitled and grandiose interpersonal style often accompanied by impulsive and reckless endangerment of oneself and others. The response modulation theory of psychopathy states that psychopathic individuals have difficulty modulating top-down attention to incorporate bottom-up stimuli that may signal important information but are irrelevant to current goals. However, it remains unclear which particular aspects of attention are impaired in psychopathy. Here, we used 2 visual search tasks that selectively tap into bottom up and top-down attention. In addition, we also looked at intertrial priming, which reflects a separate class of processes that influence attention (i.e., selection history). The research group consisted of 65 participants that were recruited from the community. Psychopathic traits were measured with the Psychopathic Personality Inventory (PPI; Uzieblo, Verschuere, & Crombez, 2007). We found that bottom-up attention was unrelated to psychopathic traits, whereas elevated psychopathic traits were related to deficits in the use of cues to facilitate top-down attention. Further, participants with elevated psychopathic traits were more strongly influenced by their previous response to the target. These results show that attentional deficits in psychopathy are largely confined to top-down attention and selection history. PMID- 26845260 TI - Temperament and externalizing behavior as mediators of genetic risk on adolescent substance use. AB - Understanding how specific genes contribute to risk for addiction remains challenging. This study tests whether childhood temperament and externalizing behavior in early adolescence account for a portion of the association between specific genetic variants and substance use problems in late adolescence. The sample consisted of 487 adolescents from the Michigan Longitudinal Study, a high risk sample (70.2% male, 81.7% European American ancestry). Polymorphisms across serotonergic (SLC6A4, 5-HTTLPR), dopaminergic (DRD4, u-VNTR), noradrenergic (SLC6A2, rs36021), and GABAergic (GABRA2, rs279858; GABRA6, rs3811995) genes were examined given prior support for associations with temperament, externalizing behavior, and substance use problems. The temperament traits behavioral control and resiliency were assessed using interviewer ratings (ages 9-11), and externalizing behavior (ages 12-14) was assessed using teacher ratings. Self reported substance use outcomes (ages 15-17) included maximum alcoholic beverages consumed in 24 hours, and frequency of past year cigarette and marijuana use. Behavioral control, resiliency, and externalizing behavior accounted for the associations between polymorphisms in noradrenergic and GABAergic genes and substance use in late adolescence. Individual differences in emotional coping and behavioral regulation represent nonspecific neurobiological underpinnings for an externalizing pathway to addiction. (PsycINFO Database Record PMID- 26845263 TI - A case of olfactory groove meningioma misdiagnosed as schizophrenia. AB - Olfactory groove meningiomas are relatively uncommon slow-growing tumors which can produce symptoms that progress insidiously. Often, patients present with personality changes and cognitive disturbances. These changes may not become apparent until the tumors become quite large, although other factors, eg, peritumoral edema and resultant brain tissue compression, influence clinical presentation. PMID- 26845261 TI - Distinct patterns of dysfunctional appetitive and aversive motivation in bipolar disorder versus schizophrenia: An event-related potential study. AB - Schizophrenia and bipolar disorder are associated with different clinical profiles of disturbances in motivation, yet few studies have compared the neurophysiological correlates of such disturbances. Outpatients with schizophrenia (n = 34), or bipolar disorder I (n = 33), and healthy controls (n = 31) completed a task in which the late positive potential (LPP), an index of motivated attention, was assessed along motivational gradients determined by apparent distance from potential rewards or punishments. Sequences of cues signaling possible monetary gains or losses appeared to loom progressively closer to the viewer; a reaction time (RT) task after the final cue determined the outcome. Controls showed the expected pattern with LPPs for appetitive and aversive cues that were initially elevated, smaller during intermediate positions, and escalated just prior to the RT task. The clinical groups showed different patterns in the final positions just prior to the RT task: the bipolar group's LPPs to both types of cues peaked relatively early during looming sequences and subsequently decreased, whereas the schizophrenia group showed relatively small LPP escalations, particularly for aversive cues. These distinct patterns suggest that the temporal unfolding of attentional resource allocation for motivationally significant events may qualitatively differ between these disorders. (PsycINFO Database Record PMID- 26845264 TI - Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness): a pragmatic 6-month trial of lithium versus quetiapine for bipolar disorder. AB - BACKGROUND: Bipolar disorder is among the 10 most disabling medical conditions worldwide. While lithium has been used extensively for bipolar disorder since the 1970s, second-generation antipsychotics (SGAs) have supplanted lithium since 1998. To date, no randomized comparative-effectiveness study has compared lithium and any SGA. METHOD: Within the duration of the study (September 2010-September 2013), participants with bipolar I or II disorder (DSM-IV-TR) were randomized for 6 months to receive lithium (n = 240) or quetiapine (n = 242). Lithium and quetiapine were combined with other medications for bipolar disorder consistent with typical clinical practice (adjunctive personalized treatment [APT], excluding any SGA for the lithium + APT group and excluding lithium or any other SGA for the quetiapine + APT group). Coprimary outcome measures included Clinical Global Impressions-Efficacy Index (CGI-EI) and necessary clinical adjustments, which measured number of changes in adjunctive personalized treatment. Secondary measures included a full range of symptoms, cardiovascular risk, functioning, quality of life, suicidal ideation and behavior, and adverse events. RESULTS: Participants improved across all measures, and over 20% had a sustained response. Primary (CGI-EI, P = .59; necessary clinical adjustments, P = .15) and secondary outcome changes were not statistically significantly different between the 2 groups. For participants with greater manic/hypomanic symptoms, CGI-EI changes were significantly more favorable with quetiapine + APT (P = .02). Among those with anxiety, the lithium + APT group had fewer necessary clinical adjustments per month (P = .02). Lithium was better tolerated than quetiapine in terms of the burden of side effects frequency (P = .05), intensity (P = .01), and impairment (P = .01). CONCLUSIONS: Despite adequate power to detect clinically meaningful differences, we found outcomes with lithium + APT and quetiapine + APT were not significantly different across 6 months of treatment for bipolar disorder. TRIAL REGISTRATION: ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304. PMID- 26845265 TI - Baseline disability and poor functioning in bipolar disorder predict worse outcomes: results from the Bipolar CHOICE study. AB - OBJECTIVE: To examine the effects of treatment on functioning impairments and quality of life and assess baseline functioning and employment status as predictors of treatment response in symptomatic individuals from the Bipolar Clinical Health Outcomes Initiative in Comparative Effectiveness (Bipolar CHOICE) study. METHOD: Bipolar CHOICE was an 11-site, 6-month randomized effectiveness study comparing lithium to quetiapine, each with adjunctive personalized treatments (APTs). We examined post hoc (1) the effects of treatment on functioning, (2) how changes in functioning differed between treatment responders and nonresponders, and (3) whether functioning and employment status mediated treatment response in 482 participants with DSM-IV-TR bipolar I or II disorder from September 2010 to September 2013. RESULTS: Treatment was associated with significant improvements in functioning and quality of life, regardless of treatment group (P values < .0001). Responders showed greater improvements in quality of life (Quality of Life Enjoyment and Satisfaction Questionnaire P values < .05) and functioning (Longitudinal Interval Follow-up Evaluation-Range of Impaired Functioning Tool P values < .05) than nonresponders. Unemployed or disabled participants at baseline had significantly greater illness severity at baseline than employed participants (P values < .05). Over the study duration, employed participants reported greater improvements in physical health and quality of life in leisure activities than both unemployed and disabled participants (P values < .05). Individuals who saw greater improvement in functioning and quality of life tended to show greater improvements in depressive and anxiety symptoms (P values <= .0001), as well as overall illness severity (P values < .001). Early (8 weeks) and very early (4 weeks) clinical changes in mood symptoms predicted changes in functioning and quality of life at 6 months (P values < .001). CONCLUSIONS: Prior disability status was associated with a worse treatment response and prospective illness course. Results implicate functioning and employment status as important markers of illness severity and likelihood of recovery in bipolar disorder, suggesting that interventions that target functional impairment may improve outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304. PMID- 26845266 TI - The effect of cariprazine on hostility associated with schizophrenia: post hoc analyses from 3 randomized controlled trials. AB - OBJECTIVE: Although most patients with schizophrenia are not aggressive, individuals with the disorder have increased risk of hostile behavior. Cariprazine, a dopamine D3 and D2 receptor partial agonist antipsychotic with preferential binding to D3 receptors, was evaluated for antihostility effects in patients with schizophrenia. METHOD: Post hoc analyses were conducted using pooled data from 3 positive randomized, placebo-controlled, phase 2/3 studies in inpatients (18-60 years) with acute exacerbation of schizophrenia according to DSM-IV-TR criteria; data were collected between 2008 and 2011. The principal post hoc outcome was mean change from baseline to week 6 on the Positive and Negative Syndrome Scale (PANSS) hostility item (P7); separate analyses adjusted for certain PANSS positive symptoms and sedation covariates. Analyses were based on the pooled intent-to-treat population (N = 1,466) using a mixed-effects model for repeated measures approach; separate analyses were conducted in subgroups categorized by baseline hostility item scores (P7: >= 2, >= 3, >= 4). RESULTS: The least squares mean difference (LSMD) in change from baseline to week 6 was statistically significant on all PANSS hostility item analyses in favor of cariprazine versus placebo: unadjusted (-0.28; P < .0001), adjusted for PANSS positive symptoms (-0.12; P < .05), adjusted for positive symptoms plus sedation (-0.12; P < .05). The magnitude of change for cariprazine increased with greater baseline hostility (LSMD vs placebo for >= 2, >= 3, >= 4 subgroups: -0.32, -0.37, -0.51, respectively; P < .01 all). CONCLUSIONS: Significant improvement on the hostility item was seen in cariprazine- versus placebo-treated patients with schizophrenia; the effect of cariprazine increased with greater levels of baseline hostility. TRIALS REGISTRATION: ClinicalTrials.gov identifiers: NCT00694707, NCT01104766, and NCT01104779. PMID- 26845267 TI - Introduction. PMID- 26845268 TI - Antidepressant treatment and risk of dementia: a population-based, retrospective case-control study. AB - OBJECTIVE: We investigated the relationship between antidepressant use and the risk of subsequent dementia development. METHOD: A population-based retrospective case-control analysis was conducted using the Taiwan National Health Insurance Research Database. From patients enrolled in the National Health Insurance program between 2005 and 2011, we identified 2 subsets: 5,394 cases, who had major depression in 1997-2004 and subsequently were diagnosed with dementia (ICD 9-CM code 290) in 2005-2011, and 5,232 controls, who had major depression in 2005 2011 but no dementia history. The proportional distributions of antidepressant use and comorbidities in the dementia case and nondementia control groups were compared. Univariable and multivariable logistic regression analyses were used to estimate the odds ratios (ORs) and 95% CIs for the association between dementia and antidepressant use. RESULTS: The dementia patients were more likely to have diabetes, hypertension, stroke, and head injury. The adjusted OR for dementia was 0.24 (95% CI, 0.22-0.27) in patients using tricyclics . By contrast, the use of selective serotonin reuptake inhibitors (SSRIs) (OR = 2.48; 95% CI, 2.27-2.71), monoamine oxidase inhibitors (MAOIs) (OR = 1.86; 95% CI, 1.47-2.36), heterocyclic antidepressants (OR = 1.44; 95% CI, 1.32-1.57), and other antidepressants (OR = 2.05; 95% CI, 1.85-2.27) was associated with an increased risk of dementia. Furthermore, as the cumulative dose was increased, tricyclic antidepressants reduced the risk of dementia, whereas SSRIs, MAOIs, heterocyclic antidepressants, and other antidepressants increased the risk of dementia. CONCLUSIONS: The incidence of dementia in patients is associated with antidepressant medication use. Treatment with tricyclic antidepressants was associated with a reduced risk of dementia, whereas treatment with SSRIs, MAOIs, heterocyclic antidepressants, and other antidepressants was associated with an increased risk of dementia. PMID- 26845269 TI - Altered topological patterns of brain networks in remitted late-onset depression: a resting-state fMRI study. AB - OBJECTIVE: We aimed to investigate the topological organization of whole-brain networks in patients with remitted late-onset depression (rLOD) and to examine the relationship between topological aberrations and performances on neuropsychological tests. METHOD: A total of 33 patients with DSM-IV-diagnosed rLOD and 31 healthy control subjects underwent resting-state functional magnetic resonance imaging scans. The whole-brain functional networks were constructed by thresholding Pearson correlation matrices of 90 brain regions, and their topological properties (ie, small-worldness, network efficiency, and nodal efficiency) were analyzed using graph theory-based approaches. Nonparametric permutation tests were further used for group comparisons of topological metrics. The patients were recruited from January to December 2007. RESULTS: Both the rLOD and control groups showed small-world architecture in the functional brain networks, suggesting a balance between functional segregation and integration. Importantly, the rLOD patients exhibited abnormal global topology in their functional brain networks (ie, increased shortest path length and decreased network efficiency) compared with the healthy controls, implying a less optimal topological organization in rLOD. Moreover, the rLOD patients showed decreased nodal efficiencies, predominantly in the frontal-striatal-occipital regions that are closely associated with the neuropathological changes in LOD. Intriguingly, we showed that the topological aberrations correlated with the neuropsychological performances in the rLOD patients. CONCLUSIONS: These results demonstrate that the topological organization of functional brain networks is disrupted in rLOD and that this disruption may contribute to disturbance in cognitive function in rLOD patients. PMID- 26845270 TI - Elevated serum levels of high-sensitivity C-reactive proteins are associated with severe delusional symptoms in a subgroup of patients with schizophrenia. PMID- 26845271 TI - Long-term deep-brain stimulation treatment for obsessive-compulsive disorder. PMID- 26845272 TI - Comparison of the effects of serotonin-norepinephrine reuptake inhibitors versus selective serotonin reuptake inhibitors on cerebrovascular events. AB - BACKGROUND: Use of selective serotonin reuptake inhibitors (SSRIs) has been associated with an increased risk of intracranial hemorrhage. However, little is known about cerebrovascular risk in users of serotonin-norepinephrine reuptake inhibitors (SNRIs). Our aim was to determine the differential risk of cerebrovascular events between SSRIs and SNRIs. METHOD: A nationwide population based cohort study was conducted in adult patients who started taking SSRIs or SNRIs during the time period 2005 through 2009. The outcome of interest was defined by the first hospitalization diagnosis for ischemic stroke (ICD-9-CM codes 433, 434, 436) or intracranial hemorrhage (ICD-9-CM codes 430, 431, 432). We used a Cox regression model with time-varying medication use and adjusted for stroke risk factors to estimate the hazard ratios (HRs) of ischemic stroke and intracranial hemorrhage associated with SNRI use, using SSRI use as a reference. RESULTS: Among 582,650 SSRI and 76,920 SNRI initiators with an average follow-up period of 3.2 years, there was a nonsignificantly increased trend toward intracranial hemorrhage (adjusted HR = 1.24 [95% CI, 0.97-1.58]) in SNRI users compared to SSRI users. The risk of ischemic stroke was comparable between the 2 treatment groups (adjusted HR = 1.01 [0.90-1.12]). Similar results were obtained in sensitivity analyses, considering a dose-response relation, allowance of a 7 day grace period between study drug discontinuation and outcome occurrence, and restriction to exclusive users, who remained on the initial treatment. In the subgroup analysis, there was an increased incidence of intracranial hemorrhages in SNRI users compared to SSRI users in patients without prior depression (adjusted HR = 1.63 [1.14-2.32]). CONCLUSIONS: Use of SNRIs is not associated with an increased risk of either ischemic stroke or intracranial hemorrhage as compared to use of SSRIs in adult patients with depression or anxiety. However, SNRIs should be used cautiously in patients without depression. PMID- 26845273 TI - Switching from 2 antipsychotics to 1 antipsychotic in schizophrenia: a randomized, double-blind, placebo-controlled study. AB - OBJECTIVE: Antipsychotic polypharmacy (APP) is employed routinely, although it remains controversial because robust evidence supporting its efficacy is lacking. In addition, it is associated with increased costs, higher antipsychotic dosing, and greater risk of side effects. Surprisingly, no prospective, randomized, double-blind studies have addressed this issue; the present investigation set out to fill this gap in knowledge. METHOD: A 12-week, double-blind, randomized, placebo-controlled, single-site study was carried out in individuals with schizophrenia or schizoaffective disorder (DSM-IV) receiving a designated primary antipsychotic plus a secondary antipsychotic, with doses stabilized for each. Individuals were randomly assigned to APP (N = 17), reflecting current treatment, or antipsychotic monotherapy (APM) (N = 18), in which the secondary antipsychotic was discontinued. Assessments occurred weekly during month 1 and every 2 weeks during months 2 and 3; the primary outcome measure was the Brief Psychiatric Rating Scale (BPRS) total score. Other measures included the Clinical Global Impressions (CGI) scale, Simpson-Angus Scale, and Barnes Akathisia Scale. The study was carried out between August 2006 and March 2011. RESULTS: Withdrawal due to clinical deterioration occurred in 1 individual receiving APP (5.8%) and in 4 individuals in the APM group (22.2%). Overall, however, there was no indication of clinical worsening with APM, as measured using BPRS and CGI scale. CONCLUSIONS: Almost 80% (n = 14) of individuals with schizophrenia or schizoaffective disorder currently receiving APP could be safely transitioned to APM with no clinical deterioration. For those who do deteriorate, risk appears greatest in the first several months. From another perspective, results also indicate that a minority of individuals benefit from APP, and research focusing on identifying this group may represent the best strategy to curb excessive use of APP. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00493233. PMID- 26845274 TI - Cigarette smoking and the onset and persistence of panic attacks during mid adulthood in the United States: 1994-2005. AB - OBJECTIVE: The current study examined the relationship between cigarette smoking (daily) and risk of onset and persistence of panic attacks over a 10-year period among adults in mid-adulthood in the United States and whether quitting smoking reduced the risk for panic attacks. METHOD: Data were drawn from the Midlife Development in the United States Survey (N = 2,101), a nationally representative sample of adults aged 25 to 74 years at baseline (wave 1, 1994-1995) who were followed up 10 years later at wave 2 (2004-2006). Psychiatric diagnoses were based on the Composite International Diagnostic Interview Short-Form (CIDI-SF [based on DSM-III-R criteria]) scales. Logistic regressions were used to evaluate the associations between smoking status and the onset and persistence of panic attack after controlling for demographic characteristics and substance use problems. RESULTS: Daily smoking in 1994 (OR = 1.9 [95% CI, 1.1-3.3]) and persistent daily smoking in 1994 and 2005 (OR = 2.6 [95% CI, 1.4-4.8]) were associated with a significantly increased likelihood of panic attacks in 2005. Moreover, smoking abstinence significantly reduced the risk of new-onset panic attacks (OR = 0.6 [95% CI, 0.4-0.97]) and persistence of panic attacks (OR = 0.2 [95% CI, 0.1-0.5]). CONCLUSIONS: The present data provide novel evidence that smoking is associated with an increased risk of panic attacks and that quitting smoking helps reduce such risk. PMID- 26845275 TI - A method for deciding about the possible safety of modafinil and armodafinil in patients with seizure disorder. AB - Modafinil or armodafinil (ar/mod) may be considered for patients with approved or unapproved indications, including excessive daytime drowsiness, fatigue, attention-deficit/hyperactivity disorder (ADHD), or addictions. Ar/mod is classified as a psychostimulant, and psychostimulants have been associated with a small risk of seizures. There is no guidance about the use of ar/mod in patients who are at risk of seizures. This article suggests how a physician may explore the safety of ar/mod if indicated in a patient at such risk. In summary, reading the prescribing information, writing to the drug manufacturer, and searching research databases suggest the following: Ar/mod and its metabolites and derivatives have dose-dependent anticonvulsant action in animal models; ar/mod is not associated with seizures as an adverse event in populations at risk, such as those with ADHD, head injury, and brain tumors; it is not associated with worsening of seizure disorder in patients with current seizure disorder; and it is not associated with seizures in overdose. These findings are reassuring. However, not all the data are of high quality, and potential ar/mod interactions with antiepileptic drugs (and other concurrent medications that affect the seizure threshold) need to be considered because ar/mod can induce the metabolism of some drugs and inhibit the metabolism of others. Decisions should be individualized, and decision-making should be a shared effort between patient and physician. PMID- 26845276 TI - Genome-wide environment interaction between depressive state and stressful life events. PMID- 26845278 TI - Communicating with colleagues and patients about acute bipolar disorder. AB - Patients with bipolar disorder require a collaborative care approach involving primary care doctors, psychiatrists, nurses, social workers, therapists, and other support to manage their illness. Psychiatric mental health nurses and advanced practice nurses provide important psychoeducation to patients regarding their diagnosis, medications, and other treatment strategies. Communication among the care team is critical to ensure that patients are adhering to treatment, being monitored for symptoms and adverse effects, and receiving follow-up and support to improve their functioning. PMID- 26845277 TI - The identification and resolution of residual symptoms in depressed primary care patients. AB - Follow the case of Mrs J, an 86-year-old patient who presents to a psychiatrist requesting a benzodiazepine for her insomnia. Like many patients who are being treated for depression, Mrs J does not recognize the residual symptoms she is experiencing, but her psychiatrist uses several approaches including metrics and collateral information to identify her continuing symptoms. Once identified, pharmacologic and nonpharmacologic treatment strategies are considered based on her symptoms and age. PMID- 26845279 TI - Functional impairment and improvement in depression. AB - Functional impairment is inherent to depression, but frequently these impairments are more resistant to treatment than the actual symptoms of depression. Unfortunately, a patient cannot truly overcome depression until these impairments are addressed. A number of validated instruments are available to help clinicians assess functional impairment and monitor it throughout treatment. Clinicians must work with patients to develop personalized short-term and long-term functional goals and determine whether pharmacologic, nonpharmacologic, or rehabilitative treatment is needed. PMID- 26845280 TI - Selective serotonin reuptake inhibitors and congenital heart anomalies: comparative cohort studies of women treated before and during pregnancy and their children. AB - BACKGROUND: Large databases and population registers are increasingly used to examine adverse birth outcomes, congenital heart anomalies, in particular, following antidepressant exposures in pregnancy. Yet many studies have failed to account for other characteristics of the women who were prescribed antidepressants. OBJECTIVE: To examine the characteristics of women who are prescribed selective serotonin reuptake inhibitors (SSRIs) in pregnancy and women who are not, associations between SSRIs prescribed in pregnancy and congenital heart anomalies, and the association between social and lifestyle characteristics of pregnant women and congenital heart anomalies. METHOD: Using data from The Health Improvement Network primary care database in the United Kingdom between January 1, 1990, and January 31, 2011, we set up a comparative study including 4 cohorts of children of women with and without different antidepressant exposures before and during pregnancy. 5,154 women were receiving SSRIs before pregnancy, 2,776 were receiving SSRIs during pregnancy, 992 were receiving other antidepressants during pregnancy, and 200,213 were receiving no antidepressants before or during pregnancy. Our primary outcome was congenital heart anomalies. RESULTS: Less than 1% of children had a record of congenital heart anomalies within 5 years of birth, and there were no significant differences related to antidepressant exposure in pregnancy (women not prescribed antidepressants versus women prescribed SSRIs in first trimester: odds ratio [OR] = 1.00; 95% CI, 0.65 1.52); however, independent of antidepressant prescribing, diabetes (OR = 2.23; 95% CI, 1.79-2.77), increasing age (OR = 1.01; 95% CI, 1.00-1.02), alcohol problem (OR = 2.58; 95% CI, 1.55-4.29, illicit drug problems (OR = 1.89; 95% CI, 1.09-3.25), and obesity (OR = 1.38; 95% CI, 1.13-1.69) were associated with an increased risk of having a child with congenital heart anomalies. CONCLUSIONS: There was no difference in congenital heart anomalies in children born to women with different antidepressant prescribing exposure status. However, we confirmed an increased risk of congenital heart anomalies in children of older women and in children of women with diabetes, a body mass index above 30 kg/m(2), and a history of alcohol and illicit drug problems independent of the prescription of antidepressants. Future research in this field must account for these characteristics. On the basis of existing evidence, advising women to stop antidepressant treatment in pregnancy may be counterproductive. PMID- 26845281 TI - A brief commentary on the Bipolar CHOICE study. PMID- 26845282 TI - Gray matter volumes and treatment response of psychotic symptoms to risperidone in antipsychotic-naive Alzheimer's disease patients. AB - OBJECTIVE: The purpose of this study was to determine whether gray matter volumes are associated with treatment response of psychotic symptoms in Alzheimer's disease (AD) patients. METHOD: Risperidone, which is commonly used as an atypical antipsychotic drug, was administered in a clinical setting for 6 weeks from April 2012 to February 2013 to 25 antipsychotic-naive AD patients with psychosis, diagnosed according to Jeste and Finkel's proposed diagnostic criteria for psychosis of Alzheimer's disease. Psychotic symptoms were rated with the Korean version of the Neuropsychiatric Inventory (K-NPI) at baseline and at 6 weeks, and treatment response was defined as the change in K-NPI score from baseline to 6 weeks. Gray matter volumes were measured with magnetic resonance imaging and voxel-based morphometry at baseline. Age, gender, years of education, total intracranial volume, apolipoprotein E genotype, dosage of risperidone, the baseline scores on the Korean version of the Mini-Mental State Examination, and the baseline psychotic and nonpsychotic symptoms scores on the K-NPI were measured as covariates of no interest. RESULTS: We found that treatment response of psychotic symptoms to risperidone in antipsychotic-naive AD patients was positively associated with both left and right putamina, left parahippocampal gyrus, and left amygdala volume after controlling covariates of no interest (uncorrected P < .001, KE > 100 voxels). CONCLUSIONS: Therefore, we conclude that gray matter volumes of putamina, left parahippocampal gyrus, and left amygdala are associated with treatment response of psychotic symptoms after 6 weeks of treatment with risperidone in antipsychotic-naive AD patients with psychosis. These results suggest that the volumes of specific gray matter regions probably contribute to treatment response of psychotic symptoms in AD patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01198093. PMID- 26845283 TI - Advisory Committee on Immunization Practices Recommended Immunization Schedules for Persons Aged 0 Through 18 Years--United States, 2016. AB - Each year, the Advisory Committee on Immunization Practices (ACIP)* reviews the recommended immunization schedules for persons aged 0 through 18 years to ensure that the schedules reflect current recommendations for Food and Drug Administration-licensed vaccines. In October 2015, ACIP approved the recommended immunization schedules for persons aged 0 through 18 years for 2016; the 2016 schedules include several changes from the 2015 immunization schedules. For 2016, the figures, footnotes, and tables will be published on the CDC immunization schedule website (http://www.cdc.gov/vaccines/schedules/index.html). This provides readers electronic access to the most current version of the schedules and footnotes on the CDC website. Health care providers are advised to use figures, tables, and the combined footnotes together. Printable versions of the 2016 immunization schedules for persons aged 0 through 18 years in several formats (e.g., portrait, landscape, and pocket-sized versions) and ordering instructions for laminated versions and "parent-friendly" schedules are available at the immunization schedule website. PMID- 26845284 TI - Digital interventions to promote self-management in adults with hypertension systematic review and meta-analysis. AB - OBJECTIVE: To synthesize the evidence for using interactive digital interventions (IDIs) to support patient self-management of hypertension, and to determine their impact on control and reduction of blood pressure. METHOD: Systematic review with meta-analysis was undertaken with a search performed in MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, Cochrane Library, DoPHER, TROPHI, Social Science Citation Index and Science Citation Index. The population was adults (>18 years) with hypertension, intervention was an IDI and the comparator was usual care. Primary outcomes were change in SBP and DBP. Only randomized controlled trials and studies published in journals and in English were eligible. Eligible IDIs included interventions accessed through a computer, smartphone or other hand-held device. RESULTS: Four out of seven studies showed a significantly greater reduction for intervention compared to usual care for SBP, with no difference found for three. Overall, IDIs significantly reduced SBP, with the weighted mean difference being -3.74 mmHg [95% confidence interval (CI) -2.19 to -2.58] with no heterogeneity observed (I-squared = 0.0%, P = 0.990). For DBP, four out of six studies indicated a greater reduction for intervention compared to controls, with no difference found for two. For DBP, a significant reduction of -2.37 mmHg (95% CI -0.40 to -4.35) was found, but considerable heterogeneity was noted (I-squared = 80.1%, P = <0.001). CONCLUSION: IDIs lower both SBP and DBP compared to usual care. Results suggest these findings can be applied to a wide range of healthcare systems and populations. However, sustainability and long-term clinical effectiveness of these interventions remain uncertain. PMID- 26845285 TI - Sex-specific vascular responses of the rat aorta: effects of moderate term (intermediate stage) streptozotocin-induced diabetes. AB - Hyperglycemia affects male and female vascular beds differently. We have previously shown that 1 week after the induction of diabetes with streptozotocin (STZ), male and female rats exhibit differences in aortic endothelial function. To examine this phenomenon further, aortic responses were studied in male and female rats 8 weeks after the induction of diabetes (intermediate stage). Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh) was measured in phenylephrine (PE) pre-contracted rat aortic rings. Concentration response curves to PE were generated before and after L-NAME, a nitric oxide synthase (NOS) inhibitor. Furthermore, mRNA expression of endothelial nitric oxide synthase (eNOS) and NADPH oxidase subunit (Nox1) were determined. At 8 weeks, diabetes impaired EDV to a greater extent in female than male aortae. Furthermore, the responsiveness to PE was significantly enhanced only in female diabetic rats, and basal NO, as indicated by the potentiation of the response to PE after L-NAME, was reduced in female diabetic rat aortae to the same levels as in males. In addition, eNOS mRNA expression was decreased, while the Nox1 expression was significantly enhanced in diabetic female rats. These results suggest that aortic function in female diabetic rats after 8 weeks exhibits a more prominent impairment and that NO may be involved. PMID- 26845286 TI - Animal-to-robot social attachment: initial requisites in a gallinaceous bird. AB - Animal-Robot Interaction experiments have demonstrated their usefulness to understand the social behaviour of a growing number of animal species. In order to study the mechanisms of social influences (from parents and peers) on behavioural development, we design an experimental setup where young quail chicks, after hatching, continuously live with autonomous mobile robots in mixed triadic groups of two chicks and one robot. As precocial birds are subject to imprinting, we compare groups where chicks meet the robot as their very first social partner, on their first day after hatching (R chicks), with groups where chicks meet a real conspecific first (C chicks), and the robot later (on the second day after hatching). We measured the behavioural synchronization between chicks and robot over three days. Afterwards, we directly tested the existence of a possible social bond between animal and robot, by performing separation-reunion behavioural tests. R chicks were more synchronized with the robot in their daily feeding-resting activities than C chicks. Moreover, R chicks emitted numerous distress calls when separated from the robot, even in the presence of another chick, whereas C chicks emitted calls only when separated from the other chick. Whether the observed chick-robot attachment bond reflects filial, or sibling imprinting of chicks towards the robot remains unclear, as the latter process is not fully understood in natural familial groups. Still, these results reveal the necessary initial conditions for stable, cohesive mixed groups of chicks and robots, a promising tool to experiment on the long-term dynamics of social behaviour. PMID- 26845287 TI - Unprecedented Solvent-Dependent Sensitivities in Highly Efficient Detection of Metal Ions and Nitroaromatic Compounds by a Fluorescent Barium Metal-Organic Framework. AB - The assembly of a fluorescent dicarboxylate ligand with a barium ion resulted in the formation of a 3D metal-organic framework, Ba5(ADDA)5(EtOH)2(H2O)3.5DMF (UPC 17), based on a 1D rod-shaped secondary building unit. The unprecedented solvent dependent sensitivities of UPC-17 for the detection of Fe(3+)/Al(3+) ions and 4 nitrophenol with high efficiency were observed for the first time. Significantly, UPC-17 exhibits superior "turn-off" detection for the Fe(3+) ion in methanol and acetone emulsions but shows "turn-on" detection in tetrahydrofuran emulsion. Furthermore, the visible color changes in the detection process make them easy to distinguish by the naked eye, which further increases its application potential. PMID- 26845288 TI - Enzyme replacement therapy with idursulfase for mucopolysaccharidosis type II (Hunter syndrome). AB - BACKGROUND: Mucopolysaccharidosis II, also known as Hunter syndrome, is a rare, X linked disease caused by a deficiency of the lysosomal enzyme iduronate-2 sulfatase, which catalyses a step in the catabolism of glycosaminoglycans. The glycosaminoglycans accumulate within tissues affecting multiple organs and physiologic systems. The clinical manifestations include neurologic involvement, severe airways obstruction, skeletal deformities and cardiomyopathy. The disease has a variable age of onset and variable rate of progression. In those with severe disease, death usually occurs in the second decade of life, whereas those individuals with less severe disease may survive into adulthood. Enzyme replacement therapy with intravenous infusions of idursulfase has emerged as a new treatment for mucopolysaccharidosis type II. This is an update of a previously published version of this review. OBJECTIVES: To evaluate the effectiveness and safety of enzyme replacement therapy with idursulfase compared to other interventions, placebo or no intervention, for treating mucopolysaccharidosis type II. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register (date of last search 23 November 2015).We also searched Embase, PubMed and the Literature Latino Americana e do Caribe em Ciencias da Saude (LILACS) (date of last search 28 November 2015). SELECTION CRITERIA: Randomised and quasi-randomised controlled trials of enzyme replacement therapy with idursulfase compared to no intervention, placebo or other options (e.g. behavioral strategies, transplantation). DATA COLLECTION AND ANALYSIS: Two authors independently screened the trials identified, appraised quality of papers and extracted data. MAIN RESULTS: One study (96 male participants) met the inclusion criteria, although the primary outcome of this review - z score for height and weight, was not assessed in the study. This trial was considered to be of overall good quality. Following 53 weeks of treatment, participants in the weekly idursulfase 0.5 mg/kg group demonstrated a significant improvement rate compared with placebo for the primary outcome: distance walked in six minutes on the basis of the sum of ranks of change from baseline, mean difference 37.00 (95% confidence interval 6.52 to 67.48). The every-other-week idursulfase 0.5 mg/kg group also showed an improvement, which was not significant compared with placebo, mean difference 23.00 (95% confidence interval -4.49 to 50.49). After 53 weeks, there was no statistical significance difference in per cent predicted forced vital capacity between the three groups and absolute forced vital capacity was significantly increased from baseline in the weekly dosing group compared to placebo, mean difference 0.16 (95% confidence interval CI 0.05 to 0.27). No difference was observed between the every-other-week idursulfase 0.5 mg/kg group and placebo.In addition, liver and spleen volumes and urine glycosaminoglycan excretion were significantly reduced from baseline by both idursulfase dosing regimens. Idursulfase was generally well tolerated, but infusion reactions did occur. Idursulfase antibodies were detected in 31.7% of participants at the end of the study and they were related to a smaller reduction in urine glycosaminoglycan levels. AUTHORS' CONCLUSIONS: The current evidence is limited. While the randomised clinical trial identified was considered to be of good quality, it failed to describe important outcomes. It has been demonstrated that enzyme replacement therapy with idursulfase is effective in relation to functional capacity (distance walked in six minutes and forced vital capacity), liver and spleen volumes and urine glycosaminoglycan excretion in people with mucopolysaccharidosis type II compared with placebo. There is no available evidence in the included study and in the literature on outcomes such as improvement in growth, sleep apnoea, cardiac function, quality of life and mortality. More studies are needed to obtain more information on the long-term effectiveness and safety of enzyme replacement therapy. PMID- 26845290 TI - Imaging Cyclotron Orbits of Electrons in Graphene. AB - Electrons in graphene can travel for several microns without scattering at low temperatures, and their motion becomes ballistic, following classical trajectories. When a magnetic field B is applied perpendicular to the plane, electrons follow cyclotron orbits. Magnetic focusing occurs when electrons injected from one narrow contact focus onto a second contact located an integer number of cyclotron diameters away. By tuning the magnetic field B and electron density n in the graphene layer, we observe magnetic focusing peaks. We use a cooled scanning gate microscope to image cyclotron trajectories in graphene at 4.2 K. The tip creates a local change in density that casts a shadow by deflecting electrons flowing nearby; an image of flow can be obtained by measuring the transmission between contacts as the tip is raster scanned across the sample. On the first magnetic focusing peak, we image a cyclotron orbit that extends from one contact to the other. In addition, we study the geometry of orbits deflected into the second point contact by the tip. PMID- 26845289 TI - A Strategy for Direct Chemical Activation of the Retinoblastoma Protein. AB - The retinoblastoma (Rb) tumor suppressor protein negatively regulates cell proliferation by binding and inhibiting E2F transcription factors. Rb inactivation occurs in cancer cells upon cyclin-dependent kinase (Cdk) phosphorylation, which induces E2F release and activation of cell cycle genes. We present a strategy for activating phosphorylated Rb with molecules that bind Rb directly and enhance affinity for E2F. We developed a fluorescence polarization assay that can detect the effect of exogenous compounds on modulating affinity of Rb for the E2F transactivation domain. We found that a peptide capable of disrupting the compact inactive Rb conformation increases affinity of the repressive Rb-E2F complex. Our results demonstrate the feasibility of discovering novel molecules that target the cell cycle and proliferation through directly targeting Rb rather than upstream kinase activity. PMID- 26845291 TI - A Proactive Response to Prescription Opioid Abuse. PMID- 26845292 TI - Bulk nanostructure of the prototypical 'good' and 'poor' solvate ionic liquids [Li(G4)][TFSI] and [Li(G4)][NO3]. AB - The bulk nanostructures of a prototypical 'good' solvate ionic liquid (SIL) and 'poor' SIL have been examined using neutron diffraction and empirical potential structure refinement (EPSR) simulated fits. The good SIL formed by a 1 : 1 mixture of lithium bis(trifluoromethylsulfonyl)imide (Li[TFSI]) in tetraglyme (G4), denoted [Li(G4)][TFSI], and the poor SIL formed from a 1 : 1 mixture of lithium nitrate (Li[NO3]) in G4, denoted [Li(G4)][NO3], have been studied. In both SILs there are strong Lewis acid-base interactions between Li(+) and ligating O atoms. However, the O atoms coordinated to Li(+) depend strongly on the counter anion present. LiO coordination numbers with G4 are 2-3 times higher for [Li(G4)][TFSI] than [Li(G4)][NO3], and conversely the LiO anion coordination number is 2-3 times higher in [Li(G4)][NO3]. In both solvates the local packing of Li around G4 O atoms are identical but these interactions are less frequent in [Li(G4)][NO3]. In both SILs, Li(+) has a distribution of coordination numbers and a wide variety of different complex structures are present. For [Li(G4)][NO3], there is a significant proportion uncoordinated G4 in the bulk; ~37% of glyme molecules have no LiO contacts and each G4 molecule coordinates to an average of 0.5 Li(+) cations. Conversely, in [Li(G4)][TFSI] only ~5% of G4 molecules lack LiO contacts and G4 molecules coordinates to an average of 1.3 Li(+) cations. Li(+) and G4 form polynuclear complexes, of the form [Lix(G4)y](x+), in both solvates. For [Li(G4)][TFSI] ~35% of Li(+) and G4 form 1 polynuclear complexes, while only ~10% of Li(+) and G4 form polynuclear complexes in [Li(G4)][NO3]. PMID- 26845293 TI - PREFACE TO AND ACKNOWLEDGMENTS FOR THE JOURNAL OF WILDLIFE DISEASES SPECIAL SUPPLEMENT: ADVANCES AND IMPROVEMENTS IN WILDLIFE WELFARE. PMID- 26845294 TI - EFFECTS OF "SWIM WITH THE TURTLES" TOURIST ATTRACTIONS ON GREEN SEA TURTLE (CHELONIA MYDAS) HEALTH IN BARBADOS, WEST INDIES. AB - Along the West Coast of Barbados a unique relationship has developed between endangered green sea turtles (Chelonia mydas) and humans. Fishermen began inadvertently provisioning these foraging turtles with fish offal discarded from their boats. Although initially an indirect supplementation, this activity became a popular attraction for visitors. Subsequently, demand for this activity increased, and direct supplementation or provisioning with food began. Food items offered included raw whole fish (typically a mixture of false herring [Harengula clupeola] and pilchard [Harengula humeralis]), filleted fish, and lesser amounts of processed food such as hot dogs, chicken, bread, or various other leftovers. Alterations in behavior and growth rates as a result of the provisioning have been documented in this population. The purpose of this study was to determine how tourism-based human interactions are affecting the overall health of this foraging population and to determine what potential health risks these interactions may create for sea turtles. Juvenile green sea turtles (n=29) were captured from four sites off the coast of Barbados, West Indies, and categorized into a group that received supplemental feeding as part of a tour (n=11) or an unsupplemented group (n=18) that consisted of individuals that were captured at sites that did not provide supplemental feeding. Following capture, a general health assessment of each animal was conducted. This included weight and morphometric measurements, a systematic physical examination, determination of body condition score and body condition index, epibiota assessment and quantification, and clinical pathology including hematologic and biochemical testing and nutritional assessments. The supplemented group was found to have changes to body condition, vitamin, mineral, hematologic, and biochemical values. Based on these results, recommendations were made to decrease negative behaviors and health impacts for turtles as a result of this provisioning. PMID- 26845295 TI - USING TAILORED TRANQUILIZER COMBINATIONS TO REDUCE STRESS ASSOCIATED WITH LARGE UNGULATE CAPTURE AND TRANSLOCATION. AB - Capture and translocation are important tools for managing and studying large ungulates. Although widely used, many established field practices cause fear and stress in subject animals that can hamper overall effectiveness and safety. Over the last 10 years we have been exploring uses of tranquilizer combinations as adjuncts to wild ungulate capture and translocation work in Colorado, USA. Our approaches have been tailored to various field applications to reduce fear and stress, facilitate handling, and improve the overall success of capture and translocation for research or management purposes. For physical capture (drop net or helicopter-net gunning) with local release, combinations of midazolam and azaperone administered immediately upon capture provide transient tranquilization and muscle relaxation during manual restraint and handling to prevent hyperthermia and capture myopathy. For extended tranquilization (during transport and overnight holding), adding a sustained-release haloperidol formulation provides calming effects for at least 24-48 h. In our assessment, appropriate and adaptive use of these tranquilizer combinations benefits captured animals without impeding management or research goals. PMID- 26845296 TI - BEST-PRACTICE GUIDELINES FOR FIELD-BASED SURGERY AND ANESTHESIA OF FREE-RANGING WILDLIFE. I. ANESTHESIA AND ANALGESIA. AB - Field anesthesia is often necessary for both invasive and noninvasive procedures on wild animals. We describe basic principles of safe anesthetic delivery, monitoring, and recovery for application in procedures involving free-ranging wildlife. For invasive procedures, the potential for immediate and lasting pain must be addressed and appropriate analgesia provided. In situations where the minimum standard of safe anesthesia and effective analgesia cannot be provided, the investigator and approving bodies should rigorously evaluate the risk to the patient against the value of the data obtained. This document is intended to serve as a resource for Institutional Animal Care and Use Committees, biologists, veterinarians, and other researchers planning projects that involve free-ranging wildlife in field conditions. PMID- 26845297 TI - BEST-PRACTICE GUIDELINES FOR FIELD-BASED SURGERY AND ANESTHESIA ON FREE-RANGING WILDLIFE. II. SURGERY. AB - The principles of surgical asepsis apply to field surgeries with few exceptions. The minimum level for performance of surgeries in the field on free-ranging animals should be the same as for domestic animals undergoing surgery in animal hospitals. Surgeries in the field are typically done as part of research and management projects and usually involve a combination of biologists and veterinarians with the possibility of conflicts in scientific cultures. This article outlines a minimum standard of care for field surgeries and will serve as a resource for Institutional Animal Care and Use Committees and biologists and veterinarians planning projects that involve surgeries on free-ranging wildlife in field conditions. PMID- 26845298 TI - ADVANCES IN ANIMAL WELFARE FOR FREE-LIVING ANIMALS. AB - Over several decades, animal welfare has grown into its own free-standing field of scientific study, from its early beginnings in laboratory animal research to eventually include exhibited animals and farm animals. While it has always been present to some degree, consideration of animal welfare for free-ranging animals has lagged behind, developing as a field of study in the last 20 yr or so. Part of that increase was that animal welfare legislation was finally applied to studies being done on free-ranging animals. But it is the appreciation by the biologists and veterinarians working on wild animals, in which the quality of their results is largely controlled by the quality of the animals they use in their studies, which has resulted in increased attention to the well-being or welfare of the animals that they use. Other important influences driving the recognition of wildlife welfare have been changes in the public's expectations of how wild animals are dealt with, a shift in focus of wildlife professionals from managing animals that can be hunted or angled to include nongame species, the decrease in participation in hunting and fishing by members of the public, and the entry of large numbers of women into fish and wildlife agencies and departments and into veterinary medicine. Technical improvements have allowed the safe capture and handling of large or dangerous animals as immobilization drugs and equipment have been developed. The increasing use of sedating drugs allows for handling of animals with reduced stress and other impacts. A number of topics, such as toe-clipping, branding, defining which taxa can or cannot feel pain, catch-and-release fishing, and more, remain controversial within wildlife science. How we treat the wild animals that we deal with defines who we are as wildlife professionals, and animal welfare concerns and techniques for free ranging animals will continue to develop and evolve. PMID- 26845299 TI - LEUKOCYTE COPING CAPACITY AS A TOOL TO ASSESS CAPTURE- AND HANDLING-INDUCED STRESS IN SCANDINAVIAN BROWN BEARS (URSUS ARCTOS). AB - Brown bears (Ursus arctos) are often captured and handled for research and management purposes. Although the techniques used are potentially stressful for the animals and might have detrimental and long-lasting consequences, it is difficult to assess their physiological impact. Here we report the use of the leukocyte coping capacity (LCC) technique to quantify the acute stress of capture and handling in brown bears in Scandinavia. In April and May 2012 and 2013, we collected venous blood samples and recorded a range of physiological variables to evaluate the effects of capture and the added impact of surgical implantation or removal of transmitters and sensors. We studied 24 brown bears, including 19 that had abdominal surgery. We found 1) LCC values following capture were lower in solitary bears than in bears in family groups suggesting capture caused relatively more stress in solitary bears, 2) ability to cope with handling stress was better (greater LCC values) in bears with good body condition, and 3) LCC values did not appear to be influenced by surgery. Although further evaluation of this technique is required, our preliminary results support the use of the LCC technique as a quantitative measure of stress. PMID- 26845300 TI - BLOOD GAS, LACTATE, AND HEMATOLOGY EFFECTS OF VENIPUNCTURE TIMING AND LOCATION AFTER MIST-NET CAPTURE OF MOURNING DOVES (ZENAIDA MACROURA), BOAT-TAILED GRACKLES (QUISCALUS MAJOR), AND HOUSE SPARROWS (PASSER DOMESTICUS). AB - Venous blood gas partial pressures, pH, bicarbonate and lactate concentrations, packed cell volume, white blood cell differential counts, and heterophil/lymphocyte ratios were measured from Mourning Doves (Zenaida macroura), Boat-tailed Grackles (Quiscalus major), and House Sparrows (Passer domesticus). Birds were bled promptly after mist-net capture and banding or following a targeted delay of 45-60 min, in order to assess the impacts of a brief holding period commonly practiced in large-scale bird banding operations. Additionally, effects of venipuncture location (basilic [=ulnar] vein versus jugular vein) were evaluated in male Boat-tailed Grackles sampled promptly after capture and banding. All comparisons were with unpaired samples; no birds were subjected to more than one venipuncture. All three species exhibited moderate improvements in blood gas and acid-base status after the delay, with reductions in lactate concentrations with or without concurrent increases in pH and bicarbonate. Boat-tailed Grackles exhibited an increased proportion of heterophils in the differential white blood cell count following a delay in sampling, suggestive of a stress leukogram. There were no significant differences between basilic and jugular venipuncture results from male Boat-tailed Grackles. Most metabolic, respiratory, and acid-base alterations were minor, but a small number of birds exhibited values (e.g., temperature-corrected pH <7.3, lactate >10 mmol/L) that could be of concern if combined with other adverse conditions. For such birds, a short delay between capture and processing could benefit their blood gas and acid-base status, although loss of time foraging or feeding young and greater activation of the hypophyseal-pituitary-adrenal axis are additional considerations. PMID- 26845301 TI - ANIMAL WELFARE FROM MOUSE TO MOOSE--IMPLEMENTING THE PRINCIPLES OF THE 3RS IN WILDLIFE RESEARCH. AB - The concept of the 3Rs (replacement, reduction, and refinement) was originally developed for improving laboratory animal welfare and is well known in biomedical and toxicologic research. The 3Rs have so far gained little attention in wildlife research, and there could be several reasons for this. First, researchers may prioritize the welfare of populations and ecosystems over the welfare of individual animals. The effects of research on individual animals can, however, impact welfare and research quality at group and population levels. Second, researchers may find it difficult to apply the 3Rs to studies of free-living wildlife because of the differences between laboratory and wild animals, species, research environment, and purpose and design of the studies. There are, however, several areas where it is possible to transfer the 3R principles to wildlife research, including replacement with noninvasive research techniques, reduction with optimized experimental design, and refinement with better methods of capture, anesthesia, and handling. Third, researchers may not have been trained in applying the 3Rs in wildlife research. This training is needed since ethics committees, employers, journal publishers, and funding agencies increasingly require researchers to consider the welfare implications of their research. In this paper, we compare the principles of the 3Rs in various research areas to better understand the possibilities and challenges of the 3Rs in wildlife research. We emphasize the importance of applying the 3Rs systematically throughout the research process. Based on experiences from laboratory research, we suggest three key factors to enhance implementation of the 3Rs in wildlife research: 1) organizational structure and management, 2) 3R awareness, and 3) research innovation, validation, and implementation. Finally, we encourage an interdisciplinary approach to incorporate the 3R principles in wildlife research. For improved animal welfare and increased research quality, researchers have moral obligations to include the 3Rs into all research areas, including wildlife research. PMID- 26845302 TI - A SCORING SYSTEM TO IMPROVE DECISION MAKING AND OUTCOMES IN THE ADAPTATION OF RECENTLY CAPTURED WHITE RHINOCEROSES (CERATOTHERIUM SIMUM) TO CAPTIVITY. AB - Ninety-four subadult and adult white rhinoceroses (Ceratotherium simum) were captured between February and October, 2009-11, in Kruger National Park and placed in holding bomas prior to translocation to other locations within South Africa. A simple three-category system was developed based on appetite, fecal consistency/volume, and behavior to assess adaptation to bomas. Individual animal and group daily median scores were used to determine trends and when rhinoceroses had successfully adapted to the boma. Seventeen rhinoceroses did not adapt to boma confinement, and 16 were released (1 mortality). No differences in boma scores were observed between rhinoceroses that adapted and those that did not, until day 8, when the first significant differences were observed (adapted score=13 versus nonadapted score=10). The time to reach a boma score determined as successful adaptation (median 19 d) matched subjective observations, which was approximately 3 wk for most rhinoceroses. Unsuccessful adaptation was indicated by an individual boma score of less than 15, typically during the first 2 wk, or a declining trend in scores within the first 7-14 d. This scoring system can be used for most locations and could also be easily adapted to other areas in which rhinoceroses are held in captivity. This tool also provides important information for assessing welfare in newly captured rhinoceroses. PMID- 26845303 TI - ASSESSMENT OF THE RATES OF INJURY AND MORTALITY IN WATERFOWL CAPTURED WITH FIVE METHODS OF CAPTURE AND TECHNIQUES FOR MINIMIZING RISKS. AB - Swan pipes, duck decoys, cage traps, cannon netting, and roundups are widely used to capture waterfowl in order to monitor populations. These methods are often regulated in countries with national ringing or banding programs and are considered to be safe, and thus justifiable given the benefits to conservation. However, few published studies have addressed how frequently injuries and mortalities occur, or the nature of any injuries. In the present study, rates of mortality and injury during captures with the use of these methods carried out by the Wildfowl & Wetlands Trust as part of conservation programs were assessed. The total rate of injury (including mild dermal abrasions) was 0.42% across all species groups, whereas total mortality was 0.1% across all capture methods. Incidence of injury varied among species groups (ducks, geese, swans, and rails), with some, for example, dabbling ducks, at greater risk than others. We also describe techniques used before, during, and after a capture to reduce stress and injury in captured waterfowl. Projects using these or other capture methods should monitor and publish their performance to allow sharing of experience and to reduce risks further. PMID- 26845304 TI - EFFECTIVENESS OF THE ANESTHETIC AQUI-S(r) 20E IN MARINE FINFISH AND ELASMOBRANCHS. AB - Immersion anesthetics are used in hatchery settings by veterinarians, field biologists, and laboratory researchers to aid in handling finfish for medical procedures, research purposes, and moderating perceived stress responses. The only Food and Drug Administration- (FDA) approved anesthetic for food fish, tricaine methanesulfonate, requires a 21-d withdrawal period prior to harvest. Ten percent eugenol (AQUI-S(r) 20E) has been gaining momentum for FDA approval because of its 0-d withdrawal time if fish are not of harvestable size within 72 h of exposure. We performed two trials to determine appropriate anesthetic doses for two cultured marine finfish: Atractoscion nobilis (white seabass, WSB) and Seriola lalandi (California yellowtail, YT). Fish were held in a treated water bath for 10 min or until opercular beat rate slowed to a rate of <2 beats/min. Based on these results, we conducted a field trial with wild Paralabrax maculatofasciatus (spotted bay bass), Paralabrax nebulifer (barred sand bass), Paralichthys californicus (California halibut), Triakis semifasciata (leopard shark), and Mustelus californicus (grey smooth-hound) at a single dosing regime, with animals held 5-10 min in anesthetic baths. Anesthetic dosing of 35-55 mg L( 1) provided relatively fast induction and good anesthetic maintenance in cultured and wild finfish. Anesthetic induction times were comparable among S. lalandi and A. nobilis at 35-mg L(-1) to 75-mg L(-1) doses, but recovery times were variable. Mortality rates of 20-90% were observed at higher doses (75 mg L(-1) and 100 mg L(-1), A. nobilis; 55 mg L(-1) and 75 mg L(-1), S. lalandi). The apparent increase in sensitivity of S. lalandi may have been associated with nutritional stress in the fish tested. There were no differences in time to anesthesia or recovery among wild finfish species tested at a single dose. Anesthetic induction, maintenance, and recovery were less predictable in the elasmobranch species tested and additional trials are needed to determine optimal dosing. PMID- 26845305 TI - B Cells and Antibodies in Transplantation. AB - Overlooked for decades, the humoral alloimmune response is increasingly recognized as a leading cause of graft loss after transplantation. However, improvement in the diagnosis of antibody-mediated rejection has not yet translated into better outcomes for transplanted patients. After an update on B cell physiology and antibody generation, the 2015 Beaune Seminar in Transplant Research challenged the conventional view of antibody-mediated rejection pathophysiology and discussed the latest promising therapeutic approaches. PMID- 26845306 TI - Prognostic Value of Preoperative Brain Natriuretic Peptide Serum Levels in Liver Transplantation. AB - BACKGROUND: Brain natriuretic peptide (BNP) serum concentration has been shown to be a preoperative predictor of postoperative outcome in high risk surgery. Whether it is able to predict early post-liver transplantation (LT) mortality in cirrhotic patients is unanswered. METHODS: Prospective monocenter observational study including all consecutive patients who received LT for cirrhosis and for whom a preoperative BNP serum dosage was available between January 2011 and December 2014. RESULTS: During the period, 207 cirrhotic patients among 525 LT were studied. The ICU and 180-day mortality rates were, respectively, 6% and 8%. Pre-LT BNP concentration, adjusted on model of end-stage liver disease (MELD) score, was an independent factor of ICU and 180-day mortality rates (for each 50 pg/mL increase; hazard ratio, 1035 [1.022-1.049]; P < 0.001 and 1.035 [1.014 1057]; P = 0.001). According to the receiver operator characteristic curve with an accuracy of 0.79 (0.66-0.93), the optimal cutoff value of pre-LT BNP serum level to predict ICU mortality was 155 pg/mL with a negative predictive value of 99%. All patients with MELD score exceeding 25 and pre-LT serum BNP level less than 155 pg/mL survived, whereas patients combining MELD score exceeding 25 and pre-LT BNP concentration exceeding 155 pg/mL had a 27% ICU mortality rate (P = 0.03). CONCLUSIONS: In cirrhotic patients, pre-LT BNP serum level was an independent predictor of post-LT ICU mortality. With its excellent negative predictive value, the use of this biomarker in combination with MELD score could be useful to better predict post-LT early outcome. PMID- 26845307 TI - Racial/Ethnic Differences in the Association Between Hospitalization and Kidney Transplantation Among Waitlisted End-Stage Renal Disease Patients. AB - BACKGROUND: Even after placement on the deceased donor waitlist, there are racial disparities in access to kidney transplant. The association between hospitalization, a proxy for health while waitlisted, and disparities in kidney transplant has not been investigated. METHODS: We used United States Renal Data System Medicare-linked data on waitlisted end-stage renal disease patients between 2005 and 2009 with continuous enrollment in Medicare Parts A & B (n = 24 581) to examine the association between annual hospitalization rate and odds of receiving a deceased donor kidney transplant. We used multilevel mixed effects models to estimate adjusted odds ratios, controlling for individual-, transplant center-, and organ procurement organization-level clustering. RESULTS: Blacks and Hispanics were more likely than whites to be hospitalized for circulatory system or endocrine, nutritional, and metabolic diseases (P < 0.001). After adjustment, compared with individuals not hospitalized, patients who were hospitalized frequently while waitlisted were less likely to be transplanted (>2 vs 0 hospitalizations/year adjusted odds ratios = 0.57; P < 0.001). Though blacks and Hispanics were more likely to be hospitalized than whites (P < 0.001), adjusting for hospitalization did not change estimated racial/ethnic disparities in kidney transplantation. CONCLUSIONS: Individuals hospitalized while waitlisted were less likely to receive a transplant. However, hospitalization does not account for the racial disparity in kidney transplantation after waitlisting. PMID- 26845309 TI - Florigen distribution determined by a source-sink balance explains the diversity of inflorescence structures in Arabidopsis. AB - The ability to continue flowering after loss of inductive environmental cues that trigger flowering is termed floral commitment. Reversible transition involving a switch from floral development back to vegetative development has been found in Arabidopsis mutants and many plant species. Although the molecular basis for floral commitment remains unclear, recent studies suggest that the persistent activity of FLOWERING LOCUS T (FT) at inflorescences is required for floral commitment in Arabidopsis thaliana. Because FT encodes a mobile signal, florigen, which is generally transported from leaves to meristems through the phloem, understanding the transportation dynamics of FT is required to explore the role of FT on floral commitment. Here we developed a transportation model of leaf- and inflorescence-derived florigen and sucrose based on pressure-flow hypothesis. Depending on the demanded level of florigen supply for floral commitment of each floral meristem, the model predicted the change in inflorescence pattern from stable commitment to flower, transient flowering, and complete reversion. FT activity in inflorescence partly suppressed floral reversion, but complete suppression was achieved only when inflorescence became a source of sucrose. This finding highlights the importance of monitoring the spatio-temporal sucrose distribution and floral stimulus to understand inflorescence development mechanism. PMID- 26845308 TI - Prolonged Mouse Cardiac Graft Cold Storage via Attenuating Ischemia-Reperfusion Injury Using a New Antioxidant-Based Preservation Solution. AB - BACKGROUND: One of the major events in ischemia-reperfusion (I/R)-induced heart injury in cardiac transplantation is the generation of reactive oxygen species. We hypothesized that a novel preservation solution called SBI-SEIIKU II (SS-II) contains 3 antioxidant reagents: L-cysteine, glycine, ascorbic acid/ascorbic acid 2-phosphate magnesium, which can block the generation of reactive oxygen species to result in a prolongation of the cold storage time via attenuating I/R injury. METHODS: C57BL/6CrSlc(B6) mice underwent syngeneic mice heterotopic heart transplantation, and the animals were derived into 3 groups: recipients with nonpreserved grafts (control group), recipients with grafts preserved in histidine-tryptophan-ketoglutarate (HTK) for 24 and 48 hours (HTK group), and recipients with grafts preserved in SS-II for 24 and 48 hours (SS-II group). RESULTS: After 48 hours of preservation, there were no grafts that survived in the HTK group; however, the SS-II group had a high survival rate. After 24 hours of preservation, SS-II decreased the oxidative damage, myocardial apoptosis, and the infiltration of macrophages and neutrophils in the cardiac grafts in the early phase and suppressed the development of myocardial fibrosis in long-term grafts compared with HTK. CONCLUSIONS: The SS-II prolongs the acceptable cold storage time and protects the myocardium from I/R injury via inhibiting oxidative stress-associated damage. We believe that this novel preservation solution may be simple and safe for use in the clinical transplantation field. PMID- 26845310 TI - Conditions for eradicating hepatitis C in people who inject drugs: A fibrosis aware model of hepatitis C virus transmission. AB - It is estimated that 80% of new hepatitis C virus (HCV) infections occur among people who inject drugs (PWID). Eradicating HCV from this population is key for the complete eradication of the disease, and the advent of simple to use, high efficacy treatments could conceivably make this scenario possible. This paper presents a mathematical model where transmission of HCV is studied in a simulated population of PWID where fibrosis progression is explicitly tracked. The stability thresholds that determine whether HCV will remain endemic or become eradicated were established numerically, and analytically on a reduced version of the model. Conditions on testing and treatment rates for eradication to occur were determined, within the context of the new high efficacy therapies. The results show that HCV eradication in the PWID population of the Vancouver, BC test scenario is achievable, but testing and especially treatment rates will need to increase significantly from current rates. Parameter estimates were drawn from published data. PMID- 26845311 TI - The Appropriate Surgical Approach to Frontotemporal Dermoid Cysts in Adult Patients. AB - Because frontotemporal dermoid cysts are superficial masses on the zygomaticofrontal suture, they are usually removed by simple direct excision in pediatric patients. Adult patients, however, require a more involved treatment approach because these cysts may be large and extend deeply into the surrounding tissue. From 2008 to 2015, 33 adult patients with frontotemporal dermoid cysts were treated in our clinic under a new treatment algorithm. Patients with a cyst smaller than 2 cm in diameter were treated using a direct excisional approach without a preoperative computed tomography (CT) evaluation. Patients with a cyst larger than 2 cm in diameter underwent a preoperative CT evaluation to determine the exact location of the cyst. If the cyst invaded the temporal fossa, a hemicoronal approach was used for excision. Cysts that did not cross the lateral orbital rim were removed using a direct excisional approach. Among the 33 patients in the study, 6 patients had cysts smaller than 2 cm in diameter, and 27 patients had cysts larger than 2 cm in diameter. Of the 27 patients with large dermoid cysts, 17 cysts showed temporal fossa invasion and 10 showed no signs of temporal fossa invasion. In all cases, the cyst was completely excised without rupture, and no instances of complications or recurrence were observed. In adults with frontotemporal dermoid cysts larger than 2 cm in diameter, preoperative CT evaluations should be performed. If the evidence suggests that a cyst has invaded the temporal fossa, a hemicoronal approach is required for complete excision. PMID- 26845312 TI - Keratopigmentation to Change the Apparent Color of the Human Eye: A Novel Indication for Corneal Tattooing. AB - BACKGROUND: Recently developed surgical techniques of keratopigmentation, assisted by femtosecond laser technology, using adequately developed micronized mineral pigments, have been reported to be efficient and conveniently safe as they are not associated with significant sight-threatening complications for changing the apparent color of the eye in cases of cosmetic therapeutic and functional keratopigmentation. We report the use of intrastromal keratopigmentation for electively changing the apparent color of the eyes, for purely cosmetic reasons. METHODS: In a case series, 7 patients underwent purely cosmetic keratopigmentation to change the apparent color of the eye. The indication was compassionate and the procedure was conducted under the tenets of the Helsinki Declaration. Superficial automated keratopigmentation, manual intralamellar keratopigmentation, and femtosecond-assisted keratopigmentation were used. In this study cosmetic outcome, patient satisfaction, visual outcomes, stability of pigmentation, and presence of any related complications are reported. RESULTS: In this study 42.8% were females, with a mean age of 40 years (27-63). In 4 patients, pigment retouch was done to improve the cosmetic outcome. Results were monitored by an independent observer with follow-up ranging from 6 months to 2.5 years. All patients expressed high satisfaction with the cosmetic outcomes, with no complications and stable visual acuity during the period of follow-up. CONCLUSIONS: As a novel indication, purely cosmetic keratopigmentation demonstrated stable pigmentation with no visual disability, high patient satisfaction, and favorable outcomes in all patients. Elective keratopigmentation seems to be a viable and convenient modality for changing the apparent color of the eye in selected cases. PMID- 26845313 TI - Matrix Regeneration Therapy: A Case Series of Corneal Neurotrophic Ulcers. AB - PURPOSE: Treating corneal neurotrophic ulcers is challenging. Topical application of matrix regeneration therapy (RGTA), which is a dextran derivative polymer and heparan sulfate analog, is a promising regenerative therapy and an alternative or additional therapeutic regimen when corneal healing is compromised. The aim of this study was to evaluate the efficacy of RGTA (Cacicol) in the treatment of 6 patients with severe neurotrophic ulcers. METHODS: We present an uncontrolled prospective case series of 6 patients (6 eyes) with severe corneal neurotrophic ulcers. Patients were treated with topical RGTA at a dose of 1 drop every second day. The main outcome measure was complete corneal epithelialization. We measured corneal thickness by anterior segment swept-source optical coherence tomography. RESULTS: Two patients (33%) showed complete corneal healing, one at 6 weeks and the other at 10 weeks. Treatment was considered failure in 4 patients (67%), and 1 patient had corneal perforation. None of the patients showed improvement in best-corrected visual acuity. There were no RGTA-related local or systemic side effects. CONCLUSIONS: Based on previous studies, RGTA seems to be a promising therapeutic agent for controlling ocular surface inflammation and promoting corneal healing. In this study, the efficacy of RGTA did not match the encouraging results from previous reports. PMID- 26845314 TI - Relationship Between Tissue Unscrolling Time and Endothelial Cell Loss. AB - PURPOSE: To assess the relationship between intraoperative unscrolling time of the donor Descemet membrane endothelial keratoplasty (DMEK) tissue and 6-month postoperative endothelial cell loss (ECL), and to determine whether donor age, scroll tightness, and the presence of an S stamp are related to unscrolling time. METHODS: Ninety-three consecutive uncomplicated DMEK surgeries performed on eyes with Fuchs endothelial dystrophy using our standardized technique (ie, prestripped tissue with or without a premarked S stamp from our eye bank, overstripping the recipient, Straiko glass injector, no-touch tap technique, and bubble of 20% SF6 gas) were evaluated. Intraoperative unscrolling times and 6 month endothelial cell densities were measured and analyzed. RESULTS: Sixty-nine cases comprised the study cohort. The median unscrolling time was 4 minutes (range: 0.8-17.5 minutes), and the median ECL was 26.9% (range: -4.3% to 80.0%). There was no relationship between unscrolling time and ECL at 6 months by the Pearson correlation coefficient (r = -0.02, P = 0.89). Younger donor age, tighter scrolls, and absence of an S stamp had no correlation with longer unscrolling times (all P > 0.05). Only 2 of 4 cases of iatrogenic primary graft failure had unscrolling times available for analysis; in this limited sample, there was no association between iatrogenic primary graft failure and unscrolling time. CONCLUSIONS: Once the DMEK tissue is safely in the anterior chamber, surgeons need not rush the "DMEK dance" because longer unscrolling times may not endanger the endothelium. PMID- 26845315 TI - Punctiform and Polychromatophilic Dominant Pre-Descemet Corneal Dystrophy. AB - PURPOSE: To describe the slit-lamp appearance and corneal confocal microscopy of autosomal dominant punctiform and polychromatophilic pre-Descemet corneal dystrophy in 3 members of the same family. METHODS: Slit-lamp examination of a 9 year-old boy showed bilateral polychromatophilic corneal opacities in a pre Descemet membrane location evenly deposited limbus to limbus, both horizontally and vertically, with an intervening clear cornea. The corneal endothelium was normal on corneal confocal microscopy, with hyperreflective opacities of various sizes located pre-Descemet membrane. Slit-lamp examination of the patient's father and brother revealed identical crystalline deposition in the pre-Descemet corneal stroma. The remainders of the eye examinations were otherwise normal in all 3 individuals, and all were asymptomatic. RESULTS: The general physical examination and laboratory investigations of the patient were all normal, as were the laboratory investigations of the other 2 family members. There was no progression in the corneal findings over 6 months of follow-up. CONCLUSIONS: These patients likely illustrate a rare autosomal dominant pre-Descemet crystalline keratopathy that has been reported only once previously. PMID- 26845316 TI - Mutational Analysis of Pre-miR-184 and hsa-mir-568 in Greek Patients With Sporadic Keratoconus. AB - PURPOSE: Despite numerous studies, the causes of keratoconus (KC) remain indefinable. Recently, polymorphisms in the seed region of miR-184 have been identified in familial severe KC and stromal thinning (endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning [EDICT]) syndrome. In this study, we conducted genotyping of microRNA genes localized in the reported KC loci, in a well-defined cohort of Greek sporadic KC patients. METHODS: A case control panel with 61 KC patients and 120 healthy controls was surveyed. DNA from each individual was genotyped for the rs41280052, located within the pre-miR-184 sequence, and hsa-mir-568 rs149509568 polymorphisms, by allele-specific polymerase chain reaction and direct sequencing. RESULTS: Regarding rs41280052, no significant association with KC was observed. The T allele of the rs41280052 was present in 5.74% of KC patients and in 8.75% of healthy controls [P = 1.00, odds ratio (OR): 1.82, 95% confidence interval: 0.11-29.66]. However, the minus allele (G) of the rs149509568 polymorphism was found to be overrepresented in KC patients (P = 0.04, odds ratio: 5.08, 95% confidence interval: 0.97-26.61). CONCLUSIONS: Our results demonstrated a significant association between sporadic KC and hsa-mir-568 rs149509568 polymorphism, suggesting a potential role of the has-mir-568 in KC pathogenesis. PMID- 26845317 TI - Cross-Linking Biomechanical Effect in Human Corneas by Same Energy, Different UV A Fluence: An Enzymatic Digestion Comparative Evaluation. AB - PURPOSE: To evaluate ex vivo the possible difference in corneal cross-linking (CXL) biomechanical effect of different ultraviolet-A (UV-A) irradiances. METHODS: The study involved 25 human donor corneas, randomly allocated to 5 groups (n = 5 each). CXL was applied with UV-A irradiances of 3, 9, 18, 30, and 45 mW/cm2, maintaining equal cumulative energy dose of 5.4 J/cm2. UV-A was delivered on half of the cornea. The nonirradiated halves served as controls. Specimens were subjected to collagenase-A enzymatic digestion. The time to complete dissolution in each specimen was recorded. RESULTS: Time to dissolution in group-A (3 mW/cm2 for 30 minutes) was 321 +/- 13.4 minutes (range: 300-330) compared with 171 +/- 8.2 (range: 165-180) for their control. In group-B (9 mW/cm2 for 10 minutes), it was 282 +/- 19.6 minutes (range: 270-315) compared with 177 +/- 6.7 (165-180) for their control. In group-C (18 mW/cm2 for 5 minutes), it was 267 +/- 19.6 minutes (range: 240-285) compared with 177 +/- 7.7 (range: 165-180) for their control. In group-D (30 mW/cm2 for 3 minutes), it was 252 +/- 12.5 minutes (range: 240-270) compared with 180 +/- 10.6 minutes (range: 165-195) for their control. In group-E (45 mW/cm2 for 2 minutes), it was 204 +/- 17.1 minutes (range: 180-225) compared with 186 +/- 8.2 minutes (range: 180-195) for their control. CONCLUSIONS: The data in this ex vivo human corneal study indicate that the biomechanical effect of CXL studied by resistance to enzymatic digestion in human corneas is comparable between irradiances of 9, 18 and 30 mW/cm and seems to be reduced at a fluence of 45 mW/cm2. PMID- 26845318 TI - Risk Factors Associated With Corneal Nerve Alteration in Type 1 Diabetes in the Absence of Neuropathy: A Longitudinal In Vivo Corneal Confocal Microscopy Study. AB - PURPOSE: The aim of this study was to determine alterations to the corneal subbasal nerve plexus (SNP) over 4 years using in vivo corneal confocal microscopy in participants with type 1 diabetes and to identify significant risk factors associated with these alterations. METHODS: A cohort of 108 individuals with type 1 diabetes and no evidence of peripheral neuropathy at enrollment underwent laser-scanning in vivo corneal confocal microscopy, ocular screening, and health and metabolic assessment at baseline, and the examinations continued for 4 subsequent annual visits. At each annual visit, 8 central corneal images of the SNP were selected and analyzed to quantify corneal nerve fiber density, corneal nerve branch density and corneal nerve fiber length. Linear mixed model approaches were fitted to examine the relationship between risk factors and corneal nerve parameters. RESULTS: A total of 96 participants completed the final visit and 91 participants completed all visits. No significant relationships were found between corneal nerve parameters and time, sex, duration of diabetes, smoking, alcohol consumption, blood pressure, or body mass index. However, corneal nerve fiber density was negatively associated with glycated hemoglobin (beta = -0.76, P < 0.01) and age (beta = -0.13, P < 0.01) and positively related to high-density lipids (beta = 2.01, P = 0.03). Higher glycated hemoglobin (beta = -1.58, P = 0.04) and age (beta = -0.23, P < 0.01) also negatively impacted corneal nerve branch density. Corneal nerve fiber length was only affected by higher age (beta = -0.06, P < 0.01). CONCLUSIONS: Glycemic control, high-density lipid, and age have significant effects on SNP structure. These findings highlight the importance of diabetic management to prevent corneal nerve damage and the capability of in vivo corneal confocal microscopy for monitoring subclinical alterations in the corneal SNP in diabetes. PMID- 26845319 TI - Serologic Markers and Ocular Staining Score in Primary Sjogren Syndrome. PMID- 26845320 TI - Ultrathin Grafts for DSAEK With a Single Microkeratome Pass. PMID- 26845321 TI - Reply to Letter to the Editor: Ultrathin Grafts for DSAEK With a Single Microkeratome Pass. PMID- 26845322 TI - The stacking dependent electronic structure and optical properties of bilayer black phosphorus. AB - By employing density-functional theory, the G0W0 method and Bethe-Salpter equation, we explore quasi-particle energy bands, optical responses and excitons of bilayer black phosphorus (BBP) with four different stacking patterns. All the structures are direct band gap semiconductors and the band gap is highly dependent on the stacking pattern, with a maximum of 1.31 eV for AB-stacking and a minimum of 0.92 eV for AD-stacking. Such dependence can be well understood by the tight-binding model in terms of the interlayer hopping. More interestingly, stacking sensitive optical absorption and exciton binding energy are observed in BBPs. For x-polarized light, more red-shift of optical adsorption appears in AA stacking and the strong exciton binding energy in the AA-stacking bilayer can be as large as 0.82 eV, that is ~1.7 times larger than that of AD-stacking bilayer. PMID- 26845323 TI - Natural Polymeric Nanoparticles for Brain-Targeting: Implications on Drug and Gene Delivery. AB - There is a broad range of biological, chemical and physical hurdles for drugs to reach the brain. Nanoparticulate drug delivery systems hold tremendous potential for diagnosis and treatment of brain disorders, including the capacity of crossing the blood-brain barrier and accessing to the brain after systemic administration. Thus, nanoparticles enable the delivery of a great variety of drugs including anticancer drugs, analgesics, anti- Alzheimer's drugs, protease inhibitors, and several macromolecules into the brain. Moreover, nanoparticles may importantly reduce the drug's toxicity and adverse effects due to an alteration of the body distribution. A very critical and important requirement for nanoparticulate brain delivery is that the employed nanoparticles are biocompatible and, moreover, rapidly biodegradable. Therefore, nanocarriers fabricated from natural polymers including polysaccharides and proteins are particularly interesting. Meeting requirements such as low cytotoxicity, abundant surface functional groups, high drug binding capacity and significant uptake into the targeted cells, natural polymer-based nanocarriers represent promising candidates for efficient drug and gene delivery to the brain. The current review highlights the latest advances achieved in developing drug-loaded polysaccharide and protein nanocarriers for brain delivery. The nanoparticles are discussed with respect to their formulation aspects, advantages, limitations, as well as the major outcomes of the in vitro and in vivo investigations. Modification of the nanoparticle surface with specific brain targeting ligands or by coating with certain surfactants for enhanced brain delivery is also reviewed. In addition, the mechanisms of the nanoparticle-mediated drug transport across the BBB are also discussed in this review. PMID- 26845324 TI - The Prominent Role of Protein-Based Delivery Systems on the Development of Cancer Treatment. AB - Nanotherapeutics has the potential of providing limitless opportunities in the area of drug and gene delivery for treatment of cancer. Although the path toward commercialization of nanoparticulate oncology drugs is long and carries significant risks, there is still considerable excitement for utilizing nanoparticle technologies in cancer drug development. Recently, there has been a significant growth in the number of nanoparticle delivery systems, used in clinical trials. Several incorporations have been established between pharmaceutical and nanotechnology companies striving to understand, develop and utilize effective interactions between nanomaterials and biological systems for cancer treatment by means of colloidal delivery systems. Protein-based nanoparticles, with one already approved and several under-development products in the commercial market, are of the pioneers of the successful employment of nanoparticulate systems in improving the cancer treatment techniques. The main reason behind the widely tendency to the usage of protein-based systems is their possibility of functionalization, biocompatibility, nonimmunogenicity, and high loading capacity for both hydrophobic and hydrophilic therapeutics. The aim of this review is to provide a comprehensive overview on the most recent findings in the area of utilization of protein-based nanoparticles for delivery of anticancer agents, as well as interpretation of the challenges encountered in the field. PMID- 26845326 TI - Endoplasmic Reticulum and Mitochondria: Independent Roles and Crosstalk in Fatty Liver Diseases and Hepatic Inflammation. AB - Proper function of the endoplasmic reticulum (ER) and mitochondria is essential for cellular homeostasis and the regulation of metabolic pathways. Perturbation of their function has been linked to pathophysiological states, including metabolic and liver diseases. Fatty liver diseases are a major health problem whose prevalence is dramatically increasing, may be induced by several factors (mainly chronic alcohol consumption, drugs or metabolic alterations), and share common features as lipid deposition, inflammation, oxidative stress and progression to more severe clinical stages, such as fibrosis, cirrhosis or even hepatocellular carcinoma. Besides their independent contributions to metabolic and hepatic pathologies, mitochondria and ER directly interact regulating each other's function, and ER-mitochondria interface is involved in several molecular pathways, as induction of autophagy and triggering of inflammatory cascades. Disturbances in these interactions have already been implicated in different human diseases, and increasing interest is arising in their role on liver illnesses. This review summarizes the current understanding regarding mitochondrial and ER implication in fatty liver diseases, focusing on lipid accumulation and inflammation, and the relevance of both the individual functions of these organelles and of ER-mitochondria interactions in such processes. In addition, it describes the clinical implications and the available therapeutic options targeting directly these organelles or associated molecular mechanisms. PMID- 26845325 TI - Site-Specific Thiol-mediated PEGylation of Streptokinase Leads to Improved Properties with Clinical Potential. AB - Streptokinase (SK) is an efficient thrombolytic agent that dissolves fibrin blood clots with clinical efficiency comparable to the high priced drug, tissue plasminogen activator (tPA). However, being of bacterial origin, its major drawbacks are its potentially high antigenicity, and relatively short circulating half-life (approximately 10-15 min). In the present investigation, an attempt has been made to address both these shortcomings by site-specific pegylation, and to obtain longer lasting thrombolytics, which are consistent with clinical requirements. Therefore, we employed available three-dimensional structural information on SK to carry out site-specific cysteine incorporation at 'optimal' surfaceexposed sites within all the three domains in streptokinase followed by pegylation with 20KDa PEG groups, and screening for biologically active variants. Interestingly, some of these SK PEG-conjugates exhibited considerably subdued immunereactivity along with enhanced in-vitro proteolytic stability profiles and extended circulating in-vivo half-lives (2 to 20-fold compared to that of native unconjugated SK) depending upon location and number of PEG-groups per molecule obtained in homogeneous form. The obtained results are a promising approach for favorably modulating immune-reactivity and half-life by cysteine- specific PEGylation of SK to achieve therapeutic attributes desirable for the treatment of different circulatory disorders, such as ischemic stroke, myocardial infarction and pulmonary embolism. PMID- 26845327 TI - Macrocyclic Compounds: Emerging Opportunities for Current Drug Discovery. AB - The macrocycles representing a unique chemical structure bridging conventional small molecules and large biomolecules, have attracted more and more attention in drug discovery over the past decade, and tremendous progress has been made toward the macrocyclization synthesis and structure diversification recently. Because of their favored size, flexibility and complexity, macrocycles can engage previously undruggable targets through numerous and spatially distributed binding interactions, and offer many privileged features including high potency, prominent selectivity, as well as favorable pharmacokinetics properties, and unique intellectual property(IP) space, and even safety profiles, etc. Currently around 70 macrocyclic molecules have been approved for clinical therapy, over 76 macrocycles are being evaluated in clinical trials from phase I to phase III. It is believed that the macrocycles will play more and more important role in the future, and provide very distinctive and promising opportunities for drug discovery along with the development of synthetic methodology, phenotypical screening, and computational studies. PMID- 26845328 TI - Thermodynamic and Kinetic Aspects Involved in the Development of Nanocarriers and Drug Delivery Systems Based on Cationic Biopolymers. AB - During the last years we have seen an increasing number of reports describing new properties and potential applications of cationic polymers and derived nanostructures. This review gives a summary of their applications in drug delivery, the preparation methods for nano and microstructures and will attempt to give a glimpse on how their structure, chemical composition and properties may be affected or modulated as to make them suitable for an intended application as drug delivery nanocarriers. The compositional complexity with the existence of several reacting groups makes cationic nanostructures critically sensitive to the contribution of thermodynamic and kinetic parameters in the determination of the type and stability of a particular structure and its ability to respond to changes in environmental conditions in the right time frame. Curiously, and contrarily to what could be expected, despite the fact that cationic polymers can form strong electrostatic interactions the contribution of the entropic component has been often found to be very important for their association with negatively charged supramolecular structures. Some general considerations indicate that when considering a complex multimolecular system like a nanocarrier containing an active ingredient it is frequently possible to find conditions under which enthalpic and entropic contributions are compensated leading to stable structures with a marginal thermodynamic stability (free energy change close to zero) which make them able to respond relatively fast to changes in the environmental conditions and therefore suitable for the design of smart drug delivery systems. Like with other nanocarriers, it should always be kept in mind that the properties of cationic nanocarriers will depend not only on their chemical composition but also on the properties of the structures formed by them. PMID- 26845329 TI - Structure-Guided Design of Antibodies. AB - Monoclonal antibodies capable of recognizing antigens with high affinity and specificity represent a wellestablished class of biological agents. Since the development of hybridoma technology in 1975, advances in recombinant DNA technologies and computational and biophysical methods have allowed us to develop a better understanding of the relationships between antibody sequence, structure, and function. These advances enable us to manipulate antibody sequences with the goal of improving upon, or creating new biological or biophysical properties. In this review we will focus on recent successes in using structure-guided computational methods to design antibodies and antibody-like molecules with optimized affinity and specificity to antigen and for enhancing protein stability. PMID- 26845330 TI - Canopy Apparent Photosynthetic Characteristics and Yield of Two Spike-Type Wheat Cultivars in Response to Row Spacing under High Plant Density. AB - In northern China, large-spike wheat (Triticum aestivum L) is considered to have significant potential for increasing yields due to its greater single-plant productivity despite its lower percentage of effective tillers, and increasing the plant density is an effective means of achieving a higher grain yield. However, with increases in plant density, the amount of solar radiation intercepted by lower strata leaves is decreased and the rate of leaf senescence is accelerated. Row spacing can be manipulated to optimize the plant spatial distribution under high plant density, therefore improving light conditions within the canopy. Consequently, field experiments were conducted from 2010 to 2012 to investigate whether changes in row spacing under high plant density led to differences in canopy apparent photosynthesis (CAP), individual leaf photosynthesis and grain yield. Two different spike-type winter wheat cultivars, Jimai22 (a small-spike cultivar as a control cultivar) and Wennong6 (a large spike cultivar), were grown at a constant plant density of 3,600,000 plants ha( 1) (a relatively higher plant density) over a wide range of row spacing as follows: 5-cm row spacing (R0), 15-cm row spacing (R1), 25-cm conventional row spacing (R2), and 35-cm row spacing (R3). The two-year investigations revealed that increased row spacing exhibited a significantly higher light transmission ratio (LT), which improved light conditions within the canopy; however, excessive light leakage losses in R2 and R3 treatments were not favorable to improved irradiation energy utilization efficiency. Aboveground biomass accumulation was influenced by row spacing. Two spike-type wheat accumulated greater biomass under 15-cm row spacing compared to other row spacing treatments, although a markedly improved photosynthetic rate (PN), effective quantum yield of photosystem II (PhiPSII) and maximal efficiency of photosystem II photochemistry (Fv/Fm) in the penultimate and third leaves were observed in R2 and R3 treatments. At the same time, a longer duration of CAP and green leaf area was maintained in R1 during grain filling. Compared with conventional row spacing, Wennong6 in R1 treatment obtained 21.0% and 19.1% higher grain yield in 2011 and 2012, respectively, while for Jimai22 it increased by 11.3% and 11.4%, respectively. A close association of yield with CAP and LAI at mid-grain filling was observed. In conclusion, for the tested growing conditions, decreasing the row spacing to an optimal distance (15 cm) maintained a longer duration of LAI and CAP during grain filling, made a better coordination of group and individual leaf photosynthesis, and accumulated higher aboveground biomass, leading to a greater grain yield. In addition, Wennong6 had a more rational canopy architecture than Jimai22 (improved LT and higher LAI) and CAP under 15-cm row spacing, leading to a higher grain yield, which indicated that the large-spike type cultivar has the potential to obtain higher yields by increasing plant density through optimum row spacing allocation (15 cm). PMID- 26845331 TI - Advancing methods for US transgender health research. AB - PURPOSE OF REVIEW: This article describes methodological challenges, gaps, and opportunities in US transgender health research. RECENT FINDINGS: Lack of large prospective observational studies and intervention trials, limited data on risks and benefits of sex affirmation (e.g., hormones and surgical interventions), and inconsistent use of definitions across studies hinder evidence-based care for transgender people. Systematic high-quality observational and intervention testing studies may be carried out using several approaches, including general population-based, health systems-based, clinic-based, venue-based, and hybrid designs. Each of these approaches has its strength and limitations; however, harmonization of research efforts is needed. Ongoing development of evidence based clinical recommendations will benefit from a series of observational and intervention studies aimed at identification, recruitment, and follow-up of transgender people of different ages, from different racial, ethnic, and socioeconomic backgrounds and with diverse gender identities. SUMMARY: Transgender health research faces challenges that include standardization of lexicon, agreed upon population definitions, study design, sampling, measurement, outcome ascertainment, and sample size. Application of existing and new methods is needed to fill existing gaps, increase the scientific rigor and reach of transgender health research, and inform evidence-based prevention and care for this underserved population. PMID- 26845332 TI - Transcriptional Profiling the 150 kb Linear Megaplasmid of Borrelia turicatae Suggests a Role in Vector Colonization and Initiating Mammalian Infection. AB - Adaptation is key for survival as vector-borne pathogens transmit between the arthropod and vertebrate, and temperature change is an environmental signal inducing alterations in gene expression of tick-borne spirochetes. While plasmids are often associated with adaptation, complex genomes of relapsing fever spirochetes have hindered progress in understanding the mechanisms of vector colonization and transmission. We utilized recent advances in genome sequencing to generate the most complete version of the Borrelia turicatae 150 kb linear megaplasmid (lp150). Additionally, a transcriptional analysis of open reading frames (ORFs) in lp150 was conducted and identified regions that were up regulated during in vitro cultivation at tick-like growth temperatures (22 degrees C), relative to bacteria grown at 35 degrees C and infected murine blood. Evaluation of the 3' end of lp150 identified a cluster of ORFs that code for putative surface lipoproteins. With a microbe's surface proteome serving important roles in pathogenesis, we confirmed the ORFs expression in vitro and in the tick compared to spirochetes infecting murine blood. Transcriptional evaluation of lp150 indicates the plasmid likely has essential roles in vector colonization and/or initiating mammalian infection. These results also provide a much needed transcriptional framework to delineate the molecular mechanisms utilized by relapsing fever spirochetes during their enzootic cycle. PMID- 26845333 TI - Four and a Half LIM Domains 1b (Fhl1b) Is Essential for Regulating the Liver versus Pancreas Fate Decision and for beta-Cell Regeneration. AB - The liver and pancreas originate from overlapping embryonic regions, and single cell lineage tracing in zebrafish has shown that Bone morphogenetic protein 2b (Bmp2b) signaling is essential for determining the fate of bipotential hepatopancreatic progenitors towards the liver or pancreas. Despite its pivotal role, the gene regulatory networks functioning downstream of Bmp2b signaling in this process are poorly understood. We have identified four and a half LIM domains 1b (fhl1b), which is primarily expressed in the prospective liver anlage, as a novel target of Bmp2b signaling. fhl1b depletion compromised liver specification and enhanced induction of pancreatic cells from endodermal progenitors. Conversely, overexpression of fhl1b favored liver specification and inhibited induction of pancreatic cells. By single-cell lineage tracing, we showed that fhl1b depletion led lateral endodermal cells, destined to become liver cells, to become pancreatic cells. Reversely, when fhl1b was overexpressed, medially located endodermal cells, fated to differentiate into pancreatic and intestinal cells, contributed to the liver by directly or indirectly modulating the discrete levels of pdx1 expression in endodermal progenitors. Moreover, loss of fhl1b increased the regenerative capacity of beta-cells by increasing pdx1 and neurod expression in the hepatopancreatic ductal system. Altogether, these data reveal novel and critical functions of Fhl1b in the hepatic versus pancreatic fate decision and in beta-cell regeneration. PMID- 26845336 TI - Presentation of Various Tactile Sensations Using Micro-Needle Electrotactile Display. AB - Tactile displays provoke tactile sensations by artificially stimulating tactile receptors. While many types of tactile displays have been developed, electrotactile displays that exploit electric stimulation can be designed to be thin, light, flexible and thus, wearable. However, the high voltages required to stimulate tactile receptors and limited varieties of possible sensations pose problems. In our previous work, we developed an electrotactile display using a micro-needle electrode array that can drastically reduce the required voltage by penetrating through the high-impedance stratum corneum painlessly, but displaying various tactile sensations was still a challenge. In this work, we demonstrate presentation of tactile sensation of different roughness to the subjects, which is enabled by the arrangement of the electrodes; the needle electrodes are on the fingertip and the ground electrode is on the fingernail. With this arrangement, the display can stimulate the tactile receptors that are located not only in the shallow regions of the finger but also those in the deep regions. It was experimentally revealed that the required voltage was further reduced compared to previous devices and that the roughness presented by the display was controlled by the pulse frequency and the switching time, or the stimulation flow rate. The proposed electrotactile display is readily applicable as a new wearable haptic device for advanced information communication technology. PMID- 26845334 TI - Unbiased Rare Event Sampling in Spatial Stochastic Systems Biology Models Using a Weighted Ensemble of Trajectories. AB - The long-term goal of connecting scales in biological simulation can be facilitated by scale-agnostic methods. We demonstrate that the weighted ensemble (WE) strategy, initially developed for molecular simulations, applies effectively to spatially resolved cell-scale simulations. The WE approach runs an ensemble of parallel trajectories with assigned weights and uses a statistical resampling strategy of replicating and pruning trajectories to focus computational effort on difficult-to-sample regions. The method can also generate unbiased estimates of non-equilibrium and equilibrium observables, sometimes with significantly less aggregate computing time than would be possible using standard parallelization. Here, we use WE to orchestrate particle-based kinetic Monte Carlo simulations, which include spatial geometry (e.g., of organelles, plasma membrane) and biochemical interactions among mobile molecular species. We study a series of models exhibiting spatial, temporal and biochemical complexity and show that although WE has important limitations, it can achieve performance significantly exceeding standard parallel simulation--by orders of magnitude for some observables. PMID- 26845335 TI - Gliding Associated Proteins Play Essential Roles during the Formation of the Inner Membrane Complex of Toxoplasma gondii. AB - The inner membrane complex (IMC) of apicomplexan parasites is a specialised structure localised beneath the parasite's plasma membrane, and is important for parasite stability and intracellular replication. Furthermore, it serves as an anchor for the myosin A motor complex, termed the glideosome. While the role of this protein complex in parasite motility and host cell invasion has been well described, additional roles during the asexual life cycle are unknown. Here, we demonstrate that core elements of the glideosome, the gliding associated proteins GAP40 and GAP50 as well as members of the GAPM family, have critical roles in the biogenesis of the IMC during intracellular replication. Deletion or disruption of these genes resulted in the rapid collapse of developing parasites after initiation of the cell cycle and led to redistribution of other glideosome components. PMID- 26845337 TI - Estimates and Predictions of Coal Workers' Pneumoconiosis Cases among Redeployed Coal Workers of the Fuxin Mining Industry Group in China: A Historical Cohort Study. AB - This research was aimed at estimating possible Coal workers' pneumoconiosis (CWP) cases as of 2012, and predicting future CWP cases among redeployed coal workers from the Fuxin Mining Industry Group. This study provided the scientific basis for regulations on CWP screening and diagnosis and labor insurance policies for redeployed coal workers of resource-exhausted mines. The study cohort included 19,116 coal workers. The cumulative incidence of CWP was calculated by the life table method. Possible CWP cases by occupational category were estimated through the average annual incidence rate of CWP and males' life expectancy. It was estimated that 141 redeployed coal workers might have suffered from CWP as of 2012, and 221 redeployed coal workers could suffer from CWP in the future. It is crucial to establish a set of feasible and affordable regulations on CWP screening and diagnosis as well as labor insurance policies for redeployed coal workers of resource-exhausted coal mines in China. PMID- 26845340 TI - Circulating Insulin-Like Growth Factor-1 Level and Ovarian Cancer Risk. AB - BACKGROUND/AIMS: Insulin-like growth factor-1 (IGF-1) has an important role in cells' proliferation, differentiation and apoptosis, and it may be involved in carcinogenesis. Several epidemiological studies assessed the association between circulating IGF-1 level and ovarian cancer risk, but there was still no conclusive finding. METHODS: A meta-analysis of published studies was performed to assess the association between circulating IGF-1 level and ovarian cancer risk. The summary odds ratio (OR) with 95% confidence interval (95%CI) was calculated through meta-analysis to evaluate the strength of the association. RESULTS: Five eligible studies were included into the meta-analysis, which involved a total of 2,028 cases of ovarian cancer and 4,625 controls. Meta analysis of total 5 studies showed that high circulating IGF-1 level was correlated with decreased risk of ovarian cancer (OR = 0.84, 95%CI 0.74-0.97, P = 0.013). After adjusting for heterogeneity, high circulating IGF-1 level was still correlated with decreased risk of ovarian cancer (OR = 0.83, 95%CI 0.72-0.95, P = 0.007). Subgroup analysis by age showed that circulating IGF-1 level was not correlated with ovarian cancer risk in women both less than 55 years and more than 55 years. However, after adjusting for heterogeneity, high circulating IGF-1 level was correlated with decreased ovarian cancer risk in women less than 55 years (OR = 0.82, 95%CI 0.72-0.94, P = 0.004). CONCLUSION: Our meta-analysis suggests that high circulating IGF-1 level may be correlated with decreased ovarian cancer risk, especially in women less than 55 years. More studies are needed to further assess the association between circulating IGF-1 level and ovarian cancer risk in the future. PMID- 26845339 TI - Effector Polymorphisms of the Sunflower Downy Mildew Pathogen Plasmopara halstedii and Their Use to Identify Pathotypes from Field Isolates. AB - The obligate biotroph oomycete Plasmopara halstedii causes downy mildew on sunflower crop, Helianthus annuus. The breakdown of several Pl resistance genes used in sunflower hybrids over the last 25 years came along with the appearance of new Pl. halstedii isolates showing modified virulence profiles. In oomycetes, two classes of effector proteins, key players of pathogen virulence, are translocated into the host: RXLR and CRN effectors. We identified 54 putative CRN or RXLR effector genes from transcriptomic data and analyzed their genetic diversity in seven Pl. halstedii pathotypes representative of the species variability. Pl. halstedii effector genes were on average more polymorphic at both the nucleic and protein levels than random non-effector genes, suggesting a potential adaptive dynamics of pathogen virulence over the last 25 years. Twenty two KASP (Competitive Allele Specific PCR) markers designed on polymorphic effector genes were genotyped on 35 isolates belonging to 14 Pl. halstedii pathotypes. Polymorphism analysis based on eight KASP markers aims at proposing a determination key suitable to classify the eight multi-isolate pathotypes into six groups. This is the first report of a molecular marker set able to discriminate Pl. halstedii pathotypes based on the polymorphism of pathogenicity effectors. Compared to phenotypic tests handling living spores used until now to discriminate Pl. halstedii pathotypes, this set of molecular markers constitutes a first step in faster pathotype diagnosis of Pl. halstedii isolates. Hence, emerging sunflower downy mildew isolates could be more rapidly characterized and thus, assessment of plant resistance breakdown under field conditions should be improved. PMID- 26845338 TI - Serum Vascular Adhesion Protein-1 Predicts End-Stage Renal Disease in Patients with Type 2 Diabetes. AB - BACKGROUND: Diabetes is the leading cause of end-stage renal disease (ESRD) worldwide. Vascular adhesion protein-1 (VAP-1) participates in inflammation and catalyzes the deamination of primary amines into aldehydes, hydrogen peroxide, and ammonia, both of which are involved in the pathogenesis of diabetic complications. We have shown that serum VAP-1 is higher in patients with diabetes and in patients with chronic kidney disease (CKD), and can predict cardiovascular mortality in subjects with diabetes. In this study, we investigated if serum VAP 1 can predict ESRD in diabetic subjects. METHODS: In this prospective cohort study, a total of 604 type 2 diabetic subjects were enrolled between 1996 to 2003 at National Taiwan University Hospital, Taiwan, and were followed for a median of 12.36 years. The development of ESRD was ascertained by linking our database with the nationally comprehensive Taiwan Society Nephrology registry. Serum VAP-1 concentrations at enrollment were measured by time-resolved immunofluorometric assay. RESULTS: Subjects with serum VAP-1 in the highest tertile had the highest incidence of ESRD (p<0.001). Every 1-SD increase in serum VAP-1 was associated with a hazard ratio of 1.55 (95%CI 1.12-2.14, p<0.01) for the risk of ESRD, adjusted for smoking, history of cardiovascular disease, body mass index, hypertension, HbA1c, duration of diabetes, total cholesterol, use of statins, ankle-brachial index, estimated GFR, and proteinuria. We developed a risk score comprising serum VAP-1, HbA1c, estimated GFR, and proteinuria, which could predict ESRD with good performance (area under the ROC curve = 0.9406, 95%CI 0.8871-0.9941, sensitivity = 77.3%, and specificity = 92.8%). We also developed an algorithm based on the stage of CKD and a risk score including serum VAP-1, which can stratify these subjects into 3 categories with an ESRD risk of 0.101%/year, 0.131%/year, and 2.427%/year, respectively. CONCLUSIONS: In conclusion, serum VAP-1 can predict ESRD and is a useful biomarker to improve risk stratification in type 2 diabetic subjects. PMID- 26845341 TI - Johnny Depp, Reconsidered: How Category-Relative Processing Fluency Determines the Appeal of Gender Ambiguity. AB - Individuals that combine features of both genders-gender blends-are sometimes appealing and sometimes not. Heretofore, this difference was explained entirely in terms of sexual selection. In contrast, we propose that part of individuals' preference for gender blends is due to the cognitive effort required to classify them, and that such effort depends on the context in which a blend is judged. In two studies, participants judged the attractiveness of male-female morphs. Participants did so after classifying each face in terms of its gender, which was selectively more effortful for gender blends, or classifying faces on a gender irrelevant dimension, which was equally effortful for gender blends. In both studies, gender blends were disliked when, and only when, the faces were first classified by gender, despite an overall preference for feminine features in all conditions. Critically, the preferences were mediated by the effort of stimulus classification. The results suggest that the variation in attractiveness of gender-ambiguous faces may derive from context-dependent requirements to determine gender membership. More generally, the results show that the difficulty of resolving social category membership-not just attitudes toward a social category-feed into perceivers' overall evaluations toward category members. PMID- 26845342 TI - Correction: Facilitative Effect of a Generalist Herbivore on the Recovery of a Perennial Alga: Consequences for Persistence at the Edge of Their Geographic Range. PMID- 26845343 TI - Pharmacokinetics of indacaterol and mometasone furoate delivered alone or in a free or fixed dose combination in healthy subjects. AB - PURPOSE: QMF149 is a fixed-dose combination of the long-acting beta2 agonist, indacaterol and the corticosteroid, mometasone furoate that is currently under development for treatment of patients with asthma and chronic obstructive pulmonary disease. We describe here a study designed to assess any pharmacokinetic (PK) and/or biopharmaceutical interaction between indacaterol and mometasone furoate when administered via the Breezhaler((r)) device, either alone or in a free or fixed combination (QMF149) in healthy adult subjects. METHODS: In this randomized, open-label, four-way crossover study, subjects were randomized to receive indacaterol acetate 150 MUg, mometasone furoate 320 MUg, alone and as free combination of the individual components, or QMF149 (indacaterol acetate 150 MUg/mometasone furoate 320 MUg) once daily for 14 days in each period, followed by a 7-day washout between periods. PK profiles were characterized on Day 14 up to 168 h post-dose. RESULTS: Indacaterol AUC0-24h,ss and Cmax,ss after administration of QMF149 were 13% [ratio: 1.13; 90%CI: 1.09, 1.17] and 18% [ratio: 1.18; 90%CI: 1.12, 1.25] higher, respectively, than indacaterol monotherapy. Mometasone furoate AUC0-24h,ss and Cmax,ss after administration of QMF149 were 14% [ratio: 1.14; 90%CI: 1.09, 1.20] and 19% [ratio: 1.19; 90%CI: 1.13, 1.26], higher, respectively than mometasone furoate monotherapy. The majority (three of four comparisons between QMF149 and monotherapy) of the 90% confidence intervals of the between-treatment ratios for AUC0-24h,ss and Cmax,ss were within the 0.80 to 1.25 interval and therefore fulfilled bioequivalence criteria. The 90% confidence interval for Cmax,ss for MF for the QMF149 vs. monotherapy comparison was [1.13, 1.26]. Although no definitive data can be provided on the basis of the present study results, it is unlikely that the small observed differences in expsoure are clinically meaningful. Multiple inhaled doses of indacaterol and mometasone furoate, when administered alone, in free combination or as QMF149 were well tolerated. CONCLUSIONS: The QMF149 fixed dose combination treatment showed comparable systemic exposure to the free combination and monotherapy treatments in terms of AUC0-24h,ss and Cmax,ss for both indacaterol and mometasone furoate, indicating an absence of clinically relevant PK or biopharmaceutical interactions. These data support further development of QMF149 without dose adjustment. PMID- 26845345 TI - Urethral Balloon Dilatation: Factors Affecting Outcomes. AB - Background/Aims/Objectives: The study aims to review our experience with balloon dilatation of urethral strictures and retrospectively analyze predictors of improved success rates. METHODS: One hundred and forty-four cases were analyzed from January 2011 to December 2012. Patients underwent balloon dilatation using 6 Fr Balloon dilator set (Cook Urological, Spencer, Ind., USA). Patients analyzed with respect to demography, uroflowmetry (Qmax) and need for auxiliary procedures in the immediate postoperative period, at 6 months and at 1 year. Comparisons were made between those who performed self-calibration against those who did not. RESULTS: Overall success rate of balloon dilatation in our study was 84.4%. Procedural failure was observed with 3 patients (2.1%). Auxiliary procedure was required in 21 cases (15.6%) during follow-up. The mean Qmax (ml/s) in those who regularly performed self-calibration (n = 73) and in those who did not perform self-calibration (n = 39) in the immediate postoperative period, at 6 months and at 1 year were 24.2 +/- 10.5, 16.5 +/- 7.5, 14.4 +/- 6.3 and 21.2 +/- 10.6, 14.5 +/- 7, 10.8 +/- 5.6, respectively. Statistical significance was noted at 1 year (p = 0.003). Lesser re-treatments were required in those who performed self calibration (12.3 vs. 20.5%). Improved success rates were noted with focal and bulbar strictures. Iatrogenic strictures and pan-anterior urethral strictures had poor outcomes despite self-calibration. CONCLUSIONS: Balloon dilation with self calibration significantly improves flow rates at 1 year and lessens auxiliary procedures required. It is simple, easy to perform under local anesthesia and repeatable in case of re-strictures. PMID- 26845344 TI - HMGB1 binds to the rs7903146 locus in TCF7L2 in human pancreatic islets. AB - The intronic SNP rs7903146 in the T-cell factor 7-like 2 gene (TCF7L2) is the common genetic variant most highly associated with Type 2 diabetes known to date. The risk T-allele is located in an open chromatin region specific to human pancreatic islets of Langerhans, thereby accessible for binding of regulatory proteins. The risk T-allele locus exhibits stronger enhancer activity compared to the non-risk C-allele. The aim of this study was to identify transcriptional regulators that bind the open chromatin region in the rs7903146 locus and thereby potentially regulate TCF7L2 expression and activity. Using affinity chromatography followed by Edman sequencing, we identified one candidate regulatory protein, i.e. high-mobility group protein B1 (HMGB1). The binding of HMGB1 to the rs7903146 locus was confirmed in pancreatic islets from human deceased donors, in HCT116 and in HEK293 cell lines using: (i) protein purification on affinity columns followed by Western blot, (ii) chromatin immunoprecipitation followed by qPCR and (iii) electrophoretic mobility shift assay. The results also suggested that HMGB1 might have higher binding affinity to the C-allele of rs7903146 compared to the T-allele, which was supported in vitro using Dynamic Light Scattering, possibly in a tissue-specific manner. The functional consequence of HMGB1 depletion in HCT116 and INS1 cells was reduced insulin and TCF7L2 mRNA expression, TCF7L2 transcriptional activity and glucose stimulated insulin secretion. These findings suggest that the rs7903146 locus might exert its enhancer function by interacting with HMGB1 in an allele dependent manner. PMID- 26845346 TI - MicroRNA transcriptome profiling of mice brains infected with Japanese encephalitis virus by RNA sequencing. AB - Japanese encephalitis (JE) is a mosquito borne viral disease, caused by Japanese encephalitis virus (JEV) infection producing severe neuroinflammation in the central nervous system (CNS) with the associated disruption of the blood brain barrier. MicroRNAs (miRNAs) are a family of 21-24 nt small non-coding RNAs that play important post-transcriptional regulatory roles in gene expression and have critical roles in virus pathogenesis. We examined the potential roles of miRNAs in JEV-infected suckling mice brains and found that JEV infection changed miRNA expression profiles when the suckling mice began showing nervous symptoms. A total of 1062 known and 71 novel miRNAs were detected in JEV-infected group, accompanied with 1088 known and 75 novel miRNAs in mock controls. Among these miRNAs, one novel and 25 known miRNAs were significantly differentially expressed, including 18 up-regulated and 8 down-regulated miRNAs which were further confirmed by real-time PCR. Gene ontology (GO) and signaling pathway analysis of the predicted target mRNAs of the modulated miRNAs showed that they are correlated with the regulation of apoptosis, neuron differentiation, antiviral immunity and infiltration of mouse brain, and the validated targets of 12 differentially expressed miRNAs were enriched for the regulation of cell programmed death, proliferation, transcription, muscle organ development, erythrocyte differentiation, gene expression, plasma membrane and protein domain specific binding. KEGG analysis further reveals that the validated target genes were involved in the Pathways in cancer, Neurotrophin signaling pathway, Toll like receptor signaling pathway, Endometrial cancer and Jak-STAT signaling pathway. We constructed the interaction networks of miRNAs and their target genes according to GO terms and KEGG pathways and the expression levels of several target genes were examined. Our data provides a valuable basis for further studies on the regulatory roles of miRNAs in JE pathogenesis. PMID- 26845347 TI - Reconsideration of the seven discrete typing units within the species Trypanosoma cruzi, a new proposal of three reliable mitochondrial clades. AB - It is generally acknowledged that Trypanosoma cruzi, responsible for Chagas disease, is structured into six or seven distinct discrete typing units (DTUs), and termed TcI through TcVI and TcBat for the seventh, by a collective of researchers. However, such structuring can be validated only when the species is analyzed over its entire distribution area with the same genetic markers. Many works have dealt with several DTUs in limited areas, generally one country, others have dealt with only one DTU over the endemic area, but no work has reported data of all DTUs over the entire endemic area. Hence, the aim of this minireview was to analyze three gene sequences, already deposited in GenBank by others, over the entire geographical distribution of Chagas disease. Two mitochondrial (CytB and COII) and one nuclear gene (Gpi) were selected (i) among those most widely used in the field, (ii) of single copy for the nuclear one, and (iii) presenting common sequences of sufficient size for applying phylogenetic tools. They were analyzed using maximum likelihood trees and phylogenetic networks. Remarkably, only three significant clusters instead of seven were found with the mitochondrial genes. With the nuclear gene, surprisingly, all seven expected clusters did not have significant bootstrap values. Moreover, DTUs TcV and TcVI were indistinguishable as were TcIII and TcIV. Additionally, we have undertaken a minireview of seventy-five publications presenting phylogenetic trees with identifiable DTUs that allowed us, together with our own results, to seriously question the structuring of T. cruzi into six or seven separated DTUs. We propose that mitochondrial typing in three clusters currently named mtTcI, mtTcII, and mtTcIII is robust whereas nuclear typing may lead to a questionable clustering but it is valuable for detecting mitochondrial introgression, heterozygous states and allelic composition. PMID- 26845348 TI - The epidemiology of the human papillomavirus related to oropharyngeal head and neck cancer. AB - OBJECTIVE: To summarize the epidemiology of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinomas (OSCC). DATA SOURCES: Articles in the English language referenced in MEDLINE/PubMed from the year 2000 onward. REVIEW METHODS: Relevant articles pertaining to the epidemiology of HPV-related OSCC were selected for review, with a particular preference for articles from 2008 onward. RESULTS: The incidence of HPV-related OSCC continues to increase in North America and Western Europe, with up to 70% of new oropharyngeal cancer cases being attributed to HPV, whereas data from the developing world remain lacking. There is evidence to support distinct risk factors for HPV-related OSCC as compared with HPV-unrelated OSCC. The long-term natural history of HPV infections remains unknown. HPV-related OSCC are associated with an improved prognosis both at the time of primary diagnosis and disease progression. There is preliminary evidence to show that HPV vaccination initiatives are effective in preventing HPV cervical infections, although data related to oral HPV infections are lacking. CONCLUSION: The epidemiology of HPV-related OSCC is evolving. Further efforts are needed to characterize the natural history of oral HPV infection and its relationship with the eventual development of HPV-associated OSCC to develop effective tools for secondary prevention. LEVEL OF EVIDENCE: NA. PMID- 26845349 TI - Cannabidiol, neuroprotection and neuropsychiatric disorders. AB - Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa. It has possible therapeutic effects over a broad range of neuropsychiatric disorders. CBD attenuates brain damage associated with neurodegenerative and/or ischemic conditions. It also has positive effects on attenuating psychotic-, anxiety- and depressive-like behaviors. Moreover, CBD affects synaptic plasticity and facilitates neurogenesis. The mechanisms of these effects are still not entirely clear but seem to involve multiple pharmacological targets. In the present review, we summarized the main biochemical and molecular mechanisms that have been associated with the therapeutic effects of CBD, focusing on their relevance to brain function, neuroprotection and neuropsychiatric disorders. PMID- 26845350 TI - MicroRNA-187-3p mitigates non-small cell lung cancer (NSCLC) development through down-regulation of BCL6. AB - Hsa-microRNA-187-3p (miR-187-3p) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-187-3p on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-187-3p on the development of NSCLC. The results indicated that miR-187-3p was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-187-3p in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay and colony formation assay, through inhibition of BCL6. In addition, miR-187-3p induced apoptosis, as indicated by concomitantly with up-regulation of the activities of caspase-3 and caspase-7, and inhibited cellular migration and invasiveness through inhibition of BCL6. Further, oncogene BCL6 was revealed to be a putative target of miR-187-3p, which was inversely correlated with miR-187 3p expression in NSCLC. Taken together, our results demonstrated that miR-187-3p played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic BCL6. PMID- 26845351 TI - G-quadruplex ligand-induced DNA damage response coupled with telomere dysfunction and replication stress in glioma stem cells. AB - Glioblastoma (GBM) is an invariably fatal brain tumor in which a small subpopulation of self-renewable glioma stem cells (GSCs) contributes to tumor propagation and relapse. Targeting GSCs could therefore have a significant clinical impact for GBM. Telomestatin is a naturally-occurring compound that preferentially impairs GSC growth by perturbing transcription and inducing a DNA damage response. Telomestatin stabilizes G-quadruplexes (G4s), which are guanine rich four-strand nucleic acid structures observed in vitro and in vivo. However, the mechanism underlying the GSC-selective nature of the DNA damage response remains unknown. Here we demonstrate that GSCs are more susceptible to telomestatin-induced telomere dysfunction and replication stress when compared with GSC-derived non-stem glioma cells (NSGCs). Telomestatin induced dissociation of the telomere-capping protein TRF2 from telomeres, leading to telomeric DNA damage in GSCs-but not in NSGCs. BIBR1532, a telomerase catalytic inhibitor, did not preferentially inhibit GSC growth, suggesting that telomestatin promotes telomere dysfunction in a telomerase-independent manner. GSCs and NSGCs had comparable levels of G4s in their nuclei, and both responded to telomestatin with phosphorylation of RPA2 at Ser33-a hallmark of replication stress. However, activation of the checkpoint kinase Chk1, induction of a DNA damage response, and subsequent growth inhibition occurred only in telomestatin-treated GSCs. These observations suggest that telomestatin impairs GSC growth through removal of TRF2 from telomeres and potent activation of the replication stress response pathway. Therefore, a novel G4-directed therapeutic strategy could specifically target cancer stem cells in GBM. PMID- 26845352 TI - Daphnetin inhibits invasion and migration of LM8 murine osteosarcoma cells by decreasing RhoA and Cdc42 expression. AB - Daphnetin, 7,8-dihydroxycoumarin, present in main constituents of Daphne odora var. marginatai, has multiple pharmacological activities including anti proliferative effects in cancer cells. In this study, using a Transwell system, we showed that daphnetin inhibited invasion and migration of highly metastatic murine osteosarcoma LM8 cells in a dose-dependent manner. Following treatment by daphnetin, cells that penetrated the Transwell membrane were rounder than non treated cells. Immunofluorescence analysis revealed that daphnetin decreased the numbers of intracellular stress fibers and filopodia. Moreover, daphnetin treatment dramatically decreased the expression levels of RhoA and Cdc42. In summary, the dihydroxycoumarin derivative daphnetin inhibits the invasion and migration of LM8 cells, and therefore represents a promising agent for use against metastatic cancer. PMID- 26845353 TI - The systemic effects of sclerostin overexpression using PhiC31 integrase in mice. AB - Sclerostin, encoded by the Sost gene, is mainly produced by osteocytes in bone and antagonizes the Wnt/beta-catenin signaling pathway, which is a requisite for bone formation. Currently, human anti-sclerostin antibodies are being tested in phase III clinical trials. In addition, serum sclerostin levels are reported to be associated with bone mineral density and fracture risk in normal individuals; however, the correlation between serum sclerostin and bone mass remains controversial. To study the effects of the continuous exposure of exogenous sclerostin on bone, a PhiC31 integrase system, which has the characteristics of site-specificity and efficiency, was applied for the delivery of the Sost gene in this study. We injected Sost-attB plasmid with or without PhiC31 integrase plasmid into the mouse tail vein using a hydrodynamic-based method. The site specific integration of the Sost gene into the mouse genome was confirmed by examining a pseudo-attP site on the hepatic genomic DNA. Sclerostin was expressed in the hepatocytes, secreted into the blood flow, and maintained at high concentrations in the mice with both Sost-attB plasmid and PhiC31 integrase plasmid injections, which was observed by serial measurement. Moreover, the mice with long-term high levels of serum sclerostin showed trabecular bone loss on micro-CT analysis. Peripheral B cell populations were not affected. Our results suggested that sclerostin could be expressed in the liver and sustained successfully at high levels in the blood by using the PhiC31 integrase system, leading to trabecular bone loss. These findings may help to further ascertain the effects of sclerostin introduced exogenously on the skeleton. PMID- 26845354 TI - The role of stabilization centers in protein thermal stability. AB - The definition of stabilization centers was introduced almost two decades ago. They are centers of noncovalent long range interaction clusters, believed to have a role in maintaining the three-dimensional structure of proteins by preventing their decay due to their cooperative long range interactions. Here, this hypothesis is investigated from the viewpoint of thermal stability for the first time, using a large protein thermodynamics database. The positions of amino acids belonging to stabilization centers are correlated with available experimental thermodynamic data on protein thermal stability. Our analysis suggests that stabilization centers, especially solvent exposed ones, do contribute to the thermal stabilization of proteins. PMID- 26845355 TI - Inhibition of MAPK and NF-kappaB signaling pathways alleviate carbon tetrachloride (CCl4)-induced liver fibrosis in Toll-like receptor 5 (TLR5) deficiency mice. AB - Current researches showed that TLR family plays an important role in liver fibrosis, yet the molecular mechanism by which this occurs is not fully explained. In this study, we investigated the role of TLR5 in carbon tetrachloride-induced liver fibrosis, and further examined wether TLR5 knockout attenuated tetrachloride-induced liver fibrosis by inhibiting hepatic stellate cells activation via modulating NF-kappaB and MAPK signaling pathways. Our results found that carbon tetrachloride induced liver function injury in WT mice with a inflammatory responses through the activation of NF-kappaB and MAPK signaling pathways, resulting in hepatic stellate cells activation. In contrast, TLR5 deficiency mice after carbon tetrachloride administration reduced NF-kappaB and MAPK signaling pathways activation, which down regulated hepatic stellate cells activation. In addition, alpha smooth muscle-actin as marker of hepatic stellate cells further indicated that TLR5 knockout mice have a lower collagen accumulation in liver tissue than WT mice after carbon tetrachloride administration, resulting in inhibition of NF-kappaB and MAPK signaling pathways activation. Moreover, in vitro experiment of hepatic stellate cells challenged with LPS or TGF-beta, further indicated that NF-kappaB and MAPK were involved in liver fibrosis development, leading to alpha-SMA expression and inflammation infiltration. However, cells from TLR5(-)(/-) may weaken phosphorylation levels of signal pathways, finally suppress progress of collagen accumulation and inflammatory responses. These results suggest a new therapeutic approach or target to protect against fibrosis caused by chronic liver diseases. PMID- 26845356 TI - Inducible CYP4F12 enhances Hepatitis C virus infection via association with viral nonstructural protein 5B. AB - Hepatitis C virus (HCV) nonstructural protein 5B (NS5B) functions as an RNA dependent RNA polymerase in the HCV replication complex derived from the endoplasmic reticulum in hepatic cells. In this study, NS5B was used as bait in a yeast two-hybrid assay to screen a human liver cDNA library. We confirmed that CYP4F12, a member of the cytochrome P450 superfamily, interacted with NS5B. Furthermore, overexpression of CYP4F12 facilitated HCV replication. In contrast, knockdown of CYP4F12 by specific shRNA decreased HCV replication and viral protein expression. Moreover, our results demonstrated that HCV infection increased the binding of the transcription factor SREBP1 to the CYP4F12 promoter and activated the promoter activity, which indicated that HCV infection increased the expression of CYP4F12 through the SREBP1 pathway. Our results showed that HCV infection induced expression of CYP4F12 protein, which bound to the HCV replication complex to facilitate viral replication. PMID- 26845357 TI - Genetic deletion of Rab27B in pancreatic acinar cells affects granules size and has inhibitory effects on amylase secretion. AB - Small G protein Rab27B is expressed in various secretory cell types and plays a role in mediating secretion. In pancreatic acinar cells, Rab27B was found to be expressed on the zymogen granule membrane and by overexpression to regulate the secretion of zymogen granules. However, the effect of Rab27B deletion on the physiology of pancreatic acinar cells is unknown. In the current study, we utilized the Rab27B KO mouse model to better understand the role of Rab27B in the secretion of pancreatic acinar cells. Our data show that Rab27B deficiency had no obvious effects on the expression of major digestive enzymes and other closely related proteins, e.g. similar small G proteins, such as Rab3D and Rab27A, and putative downstream effectors. The overall morphology of acinar cells was not changed in the knockout pancreas. However, the size of zymogen granules was decreased in KO acinar cells, suggesting a role of Rab27B in regulating the maturation of secretory granules. The secretion of digestive enzymes was moderately decreased in KO acini, compared with the WT control. These data indicate that Rab27B is involved at a different steps of zymogen granule maturation and secretion, which is distinct from that of Rab3D. PMID- 26845358 TI - Long noncoding RNA-MEG3 is involved in diabetes mellitus-related microvascular dysfunction. AB - Microvascular dysfunction is an important characteristic of diabetic retinopathy. Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes. In this study, we investigated the role of lncRNA-MEG3 in diabetes related microvascular dysfunction. We show that MEG3 expression level is significantly down-regulated in the retinas of STZ-induced diabetic mice, and endothelial cells upon high glucose and oxidative stress. MEG3 knockdown aggravates retinal vessel dysfunction in vivo, as shown by serious capillary degeneration, and increased microvascular leakage and inflammation. MEG3 knockdown also regulates retinal endothelial cell proliferation, migration, and tube formation in vitro. The role of MEG3 in endothelial cell function is mainly mediated by the activation of PI3k/Akt signaling. MEG3 up-regulation may serve as a therapeutic strategy for treating diabetes-related microvascular complications. PMID- 26845359 TI - Circular RNA expression alterations are involved in OGD/R-induced neuron injury. AB - Cerebral ischemia-reperfusion injury (IRI) is a common clinical pathological process, and it is a key step in causing further ischemic organ damage. The mechanism of cerebral IRI is still not fully understood, leading to a lack of effective treatment. It has been demonstrated that circular RNAs (circRNAs) can act as miRNA sponges and play an important role in regulating gene expression through a circRNA-miRNA-gene pathway. The specific role of circRNAs in the pathogenesis of cerebral IRI, however, is still unclear. Thus, in the present study, we investigated circRNA expression differences in HT22 cells with oxygen glucose deprivation/reoxygenation (OGD/R) versus normal controls. The results from circRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model (p < 0.05) compared with the control group. Among them, 3 were significantly up-regulated, and the other 12 were down-regulated. Furthermore, the up-regulated expression of mmu-circRNA-015947 was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analysis revealed that up-regulated expression of mmu-circRNA-015947 could interact with miRNAs (mmu-miR-188-3p, mmu-miR-329-5p, mmu-miR-3057-3p, mmu-miR-5098 and mmu-miR-683) and thereby enhance target gene expression. KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in apoptosis-related, metabolism-related and immune-related pathways, which are known to be involved in the pathogenesis of IRI. This research suggests that the overlapping expression of mmu-circRNA-015947 might be involved in the process of cerebral IRI and presents a novel molecular target for clinical therapy. PMID- 26845360 TI - Rheumatoid arthritis: past, present and future approaches to treating the disease. PMID- 26845361 TI - Source apportionment and health effect of NOx over the Pearl River Delta region in southern China. AB - As one of the most notorious atmospheric pollutants, NOx not only promotes the formation of ozone but also has adverse health effects on humans. It is therefore of great importance to study the sources of NOx and its effects on human health. The Comprehensive Air Quality Model (CAMx) modeling system and ozone source apportionment technology (OSAT) were used to study the contribution of NOx from different emission sources over southern China. The results indicate that heavy duty diesel vehicles (HDDVs) and industrial point sources are the two major local NOx sources, accounting for 30.8% and 18.5% of local NOx sources, respectively. In Hong Kong, marine emissions contributed around 43.4% of local NOx in 2011. Regional transport is another important source of this pollutant, especially in February and November, and it can contribute over 30% of ambient NOx on average. Power plant point emission is an significant regional source in Zhuhai, Zhongshan and Foshan. The total emission sources are estimated to cause 2119 (0-4405) respiratory deaths and 991 (0-2281) lung cancer deaths due to long-term exposure to NOx in the Pearl River Delta region. Our results suggest that local governments should combine their efforts and vigorously promote further reduction of NOx emissions, especially for those sources that make a substantial contribution to NOx emissions and affect human health: HDDV, LDGV, industrial point sources and marine sources. PMID- 26845362 TI - Occurrence and levels of polybrominated diphenyl ethers in surface sediments from the Yellow River Estuary, China. AB - A total of 21 surface sediments collected from the Yellow River Estuary, China were analyzed for 40 kinds of polybrominated diphenyl ethers (PBDEs) using gas chromatography-mass spectrometry (GC-MS). Their levels, spatial distribution, congener profiles and possible sources were investigated. Only ten congeners were detected in the sediments. The total concentrations of the lower brominated BDEs (?PBDEslow, PBDEs excluding BDE 209) and BDE 209 ranged from 0.482 ng/g to 1.07 ng/g and 1.16-5.40 ng/g, with an average value of 0.690 and 2.79 ng/g, respectively, which were both at the low end of the global contamination level. The congener profiles were dominated by BDE 209, with the average value accounting for 79.2% of the total PBDEs in the sediment samples. Among the nine lower brominated BDE congeners, BDE 47, 99 and 183 had high abundances. Although the commercial Penta/Octa-BDE products have been banned in most countries, the residual commercial Penta/Octa/Deca-BDE products and the debromination of highly brominated BDE compounds such as BDE 209 were still found to be the possible sources for the trace level of PBDEs in the present study area. In spite of the gradual removal of the commercial PBDEs in the world, the present research results further suggested that scientific attention should not be reduced on the issue of environmental contamination caused by these outdated chemical compounds. PMID- 26845363 TI - Acute phenanthrene toxicity to juvenile diploid and triploid African catfish (Clarias gariepinus): Molecular, biochemical, and histopathological alterations. AB - Information on the biological responses of polyploid animals towards environmental contaminants is scarce. This study aimed to compare reproductive axis-related gene expressions in the brain, plasma biochemical responses, and the liver and gill histopathological alterations in diploid and triploid full-sibling juvenile African catfish (Clarias gariepinus). Fish were exposed for 96 h to one of the two waterborne phenanthrene (Phe) concentrations [mean measured (SD): 6.2 (2.4) and 76 (4.2) MUg/L]. In triploids, exposure to 76 MUg/L Phe increased mRNA level of fushi tarazu-factor 1 (ftz-f1). Expression of tryptophan hydroxylase2 (tph2) was also elevated in both ploidies following the exposure to 76 MUg/L Phe compared to the solvent control. In triploids, 76 MUg/L Phe increased plasma alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) levels compared to the other Phe-exposed group. It also elevated lactate and glucose contents relative to the other groups. In diploids, however, biochemical biomarkers did not change. Phenanthrene exposures elevated glycogen contents and the prevalence of histopathological lesions in the liver and gills of both ploidies. This study showed substantial differences between diploids and triploids on biochemical and molecular biomarker responses, but similar histopathological alterations following acute Phe exposures. PMID- 26845365 TI - Effect of UV irradiation on the aggregation of TiO2 in an aquatic environment: Influence of humic acid and pH. AB - The behavior of photoactive TiO2 nanoparticles in an aquatic environment under UV irradiation was investigated. When there was no UV light irradiation, the attachment of humic acid (HA) onto the TiO2 nanoparticles improved their stability due to an increase in the electrostatic and steric repulsions between the particles. However, our study demonstrated that UV light clearly influenced the aggregation of TiO2 nanoparticles. Half an hour of UV irradiation caused the particles to aggregate from 331.0 nm to 1505.0 nm at a pH of 3.0. Similarly, the particles aggregated from 533.2 nm to 1037.0 nm at a pH of 6.5 and from 319.0 nm to 930.0 nm at a pH of 9.0. The aggregation continued with increased irradiation time, except for the condition at pH 3.0, which demonstrated disaggregation. Furthermore, we determined that the photocatalytic degradation of the HA dominated the behavior of TiO2 in our study. From the results of HA removal and 3DEEM fluorescence spectra data for the solution, a change in the HA was in accordance with the size change of the TiO2. The results illustrated that the UV irradiation affected the behavior of light-active nanomaterial (such as TiO2) in an aquatic system, thus influencing their bioavailability and reactivity. PMID- 26845364 TI - Forensic assessment of polycyclic aromatic hydrocarbons at the former Sydney Tar Ponds and surrounding environment using fingerprint techniques. AB - Polycyclic aromatic hydrocarbons (PAHs) were assessed spatially and temporally within and adjacent to a former coking and steel manufacturing facility in Sydney, Nova Scotia, Canada. Concentrations of PAHs were measured in surface soils, marine and estuary sediments prior to and during remediation of the Sydney Tar Ponds (STPs) site which was contaminated by nearly a century of coking and steel production. Previous studies identified PAHs in surficial marine sediments within Sydney Harbour, which were considered to be derived from STP discharges. Numerous PAH fingerprint techniques (diagnostic ratios, principal component analysis, quantitative and qualitative analysis) were applied to soil and sediment samples from the STPs and surrounding area to identify common source apportionment of PAHs. Results indicate coal combustion (from historical residential, commercial and industrial uses) and coal handling (from historic on site stockpiling and current coal transfer and shipment facilities) are likely the principal source of PAHs found in urban soils and marine sediments, consistent with current and historical activities near these sites. However, PAH fingerprints associated with STP sediments correlated poorly with those of urban soils and marine sediments, but were similar to coal tar, historically consistent with by-products produced by the former coking operations. This study suggests PAH contamination of Sydney Harbour sediments and urban soils is largely unrelated to historic coking operations or recent remediation of the STPs site, but rather a legacy of extensive use of coal for a variety of activities. PMID- 26845366 TI - Mercury in terrestrial forested systems with highly elevated mercury deposition in southwestern China: The risk to insects and potential release from wildfires. AB - Forests are considered a pool of mercury in the global mercury cycle. However, few studies have investigated the distribution of mercury in the forested systems in China. Tieshanping forest catchment in southwest China was impacted by mercury emissions from industrial activities and coal combustions. Our work studied mercury content in atmosphere, soil, vegetation and insect with a view to estimating the potential for mercury release during forest fires. Results of the present study showed that total gaseous mercury (TGM) was highly elevated and the annual mean concentration was 3.51 +/- 1.39 ng m(-2). Of the vegetation tissues, the mercury concentration follows the order of leaf/needle > root > bark > branch > bole wood for each species. Total ecosystem mercury pool was 103.5 mg m(-2) and about 99.4% of the mercury resides in soil layers (0-40 cm). The remaining 0.6% (0.50 mg m(-2)) of mercury was stored in biomass. The large mercury stocks in the forest ecosystem pose a serious threat for large pluses to the atmospheric mercury during potential wildfires and additional ecological stress to forest insect: dung beetles, cicada and longicorn, with mercury concentration of 1983 +/ 446, 49 +/- 38 and 7 +/- 5 ng g(-1), respectively. Hence, the results obtained in the present study has implications for global estimates of mercury storage in forests, risks to forest insect and potential release to the atmosphere during wildfires. PMID- 26845367 TI - A proteomic study on liver impairment in rat pups induced by maternal microcystin LR exposure. AB - There is mounting evidence indicating that microcystins (MCs) are heptapeptide toxins. Recent studies have also shown that MCLR can transfer from mother to offspring, but it is unclear whether maternal MCLR can influence the liver of offspring or not. In this study, pregnant SD rats were injected intraperitoneally with a saline solution (control) or 10 MUg/kg MCLR per day from gestational day 8 (GD8) to postnatal day 15 (PD15) for a total of 4 weeks. 2-DE and MALDI-TOF-TOF mass spectrometry were used to screen for MCLR target proteins in the livers of rat pups. Our results demonstrated that MCLR could accumulate in the livers of neonatal rats. Proteomics studies also showed that MCLR significantly influenced many proteins, including those involved in the cytoskeleton, metabolism and particularly oxidative stress. In addition, MCLR induced cellular structural damage and resulted in the production of intracellular reactive oxygen species (ROS) and lipid peroxidation. Moreover, protein phosphatase (PP) activity was inhibited and some serum biochemistry parameters were altered. These results suggest an early molecular mechanism behind the hepatotoxicity induced by maternal MC exposure and highlight the importance of monitoring MC concentrations in new-born mammals. PMID- 26845368 TI - Nutrients versus emerging contaminants-Or a dynamic match between subsidy and stress effects on stream biofilms. AB - Freshwater ecosystems are threatened by multiple anthropogenic stressors, which might be differentiated into two types: those that reduce biological activity at all concentrations (toxic contaminants), and those that subsidize biological activity at low concentrations and reduce it at high concentrations (assimilable contaminants). When occurring in mixtures, these contaminants can have either antagonistic, neutral or synergistic effects; but little is known on their joint effects. We assessed the interaction effects of a mixture of assimilable and toxic contaminants on stream biofilms in a manipulative experiment using artificial streams, and following a factorial design with three nutrient levels (low, medium or high) and either presence or absence of a mixture of emerging contaminants (ciprofloxacin, erythromycin, diclofenac, methylparaben, and sulfamethoxazole). We measured biofilm biomass, basal fluorescence, gross primary production and community respiration. Our initial hypotheses were that biofilm biomass and activity would: increase with medium nutrient concentrations (subsidy effect), but decrease with high nutrient concentrations (stress effect) (i); decrease with emerging contaminants, with the minimum decrease at medium nutrient concentrations (antagonistic interaction between nutrients subsidy and stress by emerging contaminants) and the maximum decrease at high nutrient concentrations (synergistic interaction between nutrients and emerging contaminants stress) (ii). All the measured variables responded linearly to the available nutrients, with no toxic effect at high nutrient concentrations. Emerging contaminants only caused weak toxic effects in some of the measured variables, and only after 3-4 weeks of exposure. Therefore, only antagonistic interactions were observed between nutrients and emerging contaminants, as medium and high nutrient concentrations partly compensated the harmful effects of emerging contaminants during the first weeks of the experiment. Our results show that contaminants with a subsidy effect can alleviate the effects of toxic contaminants, and that long term experiments are required to detect stress effects of emerging contaminants at environmentally relevant concentrations. PMID- 26845370 TI - Simulation study of a chaotic cavity transducer based virtual phased array used for focusing in the bulk of a solid material. AB - In acoustic and ultrasonic non-destructive testing techniques, it is sometimes beneficial to concentrate sound energy at a chosen location in space and at a specific instance in time, for example to improve the signal-to-noise ratio or activate the nonlinearity of damage features. Time Reversal (TR) techniques, taking advantage of the reversible character of the wave equation, are particularly suited to focus ultrasonic waves in time and space. The characteristics of the energy focusing in solid media using principles of time reversed acoustics are highly influenced by the nature and dimensions of the medium, the number of transducers and the length of the received signals. Usually, a large number of transducers enclosing the domain of interest is needed to improve the quality of the focusing. However, in the case of highly reverberant media, the number of transducers can be reduced to only one (single channel TR). For focusing in a non-reverberant medium, which is impossible when using only one source, an adaptation of the single-channel reciprocal TR procedure has been recently suggested by means of a Chaotic Cavity Transducer (CCT), a single element transducer glued on a cavity of chaotic shape. In this paper, a CCT is used to focus elastic energy, at different times, in different points along a predefined line on the upper surface of a thick solid sample. Doing so, all focusing points can act as a virtual phased array transducer, allowing to focus in any point along the depth direction of the sample. This is impossible using conventional reciprocal TR, as you need to have access to all points in the bulk of the material for detecting signals to be used in the TR process. To asses and provide a better understanding of this concept, a numerical study has been developed, allowing to verify the basic concepts of the virtual phased array and to illustrate multi-component time reversal focusing in the bulk of a solid material. PMID- 26845369 TI - Impact of chloride on denitrification potential in roadside wetlands. AB - Developed landscapes are exposed to changes in hydrology and water chemistry that limit their ability to mitigate detrimental impacts to coastal water bodies, particularly those that result from stormwater runoff. The elevated level of impervious cover increases not only runoff but also contaminant loading of nutrients, metals, and road salt used for deicing to water bodies. Here we investigate the impact that road salt has on denitrification in roadside environments. Sediments were collected from a series of forested and roadside wetlands and acclimated with a range of Cl(-) concentrations from 0 to 5000 mg L( 1) for 96 h. Denitrification rates were measured by the isotope pairing technique using (15)N-NO3(-), while denitrifying community structures were compared using terminal restriction fragment length polymorphism (T-RFLP) of nitrous oxide reductase genes (nosZ). Chloride significantly (p < 0.05) inhibited denitrification in forested wetlands at a Cl(-) dosage of 2500 or 5000 mg L(-1), but the decrease in denitrification rates was less and not significant for the roadside wetlands historically exposed to elevated concentrations of Cl(-). The difference could not be attributed to other significant changes in conditions, such as DOC concentrations, N species concentrations, or pH levels. Denitrifying communities, as measured by T-RFs of the nosZ gene, in the roadside wetlands with elevated concentration of Cl(-) were distinctly different and more diverse compared to forested wetlands, and also different in roadside wetlands after 96 h exposures to Cl(-). The shifts in denitrifying communities seem to minimize the decrease in denitrification rates in the wetlands previously exposed to Cl. As development results in more Cl(-) use and exposure to a broad range of natural or manmade wetland structures, an understanding of the seasonal effect of Cl on denitrification processes in these systems would aid in design or mitigation of the effects on N removal rates. PMID- 26845372 TI - SMFM 2016: Meeting highlights-Thursday (Podcast). PMID- 26845371 TI - Tomoelastography by multifrequency wave number recovery from time-harmonic propagating shear waves. AB - Palpation is one of the most sensitive, effective diagnostic practices, motivating the quantitative and spatially resolved determination of soft tissue elasticity parameters by medical ultrasound or MRI. However, this so-called elastography often suffers from limited anatomical resolution due to noise and insufficient elastic deformation, currently precluding its use as a tomographic modality on its own. We here introduce an efficient way of processing wave images acquired by multifrequency magnetic resonance elastography (MMRE), which relies on wave number reconstruction at different harmonic frequencies followed by their amplitude-weighted averaging prior to inversion. This results in compound maps of wave speed, which reveal variations in tissue elasticity in a tomographic fashion, i.e. an unmasked, slice-wise display of anatomical details at pixel-wise resolution. The method is demonstrated using MMRE data from the literature including abdominal and pelvic organs such as the liver, spleen, uterus body and uterus cervix. Even in small regions with low wave amplitudes, such as nucleus pulposus and spinal cord, elastic parameters consistent with literature values were obtained. Overall, the proposed method provides a simple and noise-robust strategy of in-plane wave analysis of MMRE data, with a pixel-wise resolution producing superior detail to MRE direct inversion methods. PMID- 26845373 TI - The Role of MgCl2 as a Lewis Base in ROMgCl-MgCl2 Electrolytes for Magnesium-Ion Batteries. AB - A series of strong Lewis acid-free alkoxide/siloxide-based Mg electrolytes were deliberately developed with remarkable oxidative stability up to 3.5 V (vs. Mg/Mg(2+)). Despite the perception of ROMgCl (R=alkyl, silyl) as a strong base, ROMgCl acts like Lewis acid, whereas the role of MgCl2 in was unambiguously demonstrated as a Lewis base through the identification of the key intermediate using single crystal X-ray crystallography. This Lewis-acid-free strategy should provide a prototype system for further investigation of Mg-ion batteries. PMID- 26845374 TI - Youth access to cigarettes in six sub-Saharan African countries. AB - OBJECTIVE: Tobacco smoking is initiated and established mostly during adolescence. The World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) Article 16 outlines the obligation of parties to prohibit the sale of tobacco products to minors. This study examined where and how student smokers obtain cigarettes. METHODS: We examined Global Youth Tobacco Survey (GYTS) data from 2009 to 2011 on cigarette access among students aged 13-15 in six sub Saharan African countries. RESULTS: In all countries analyzed, over 20% of student smokers obtained their cigarettes in a store or shop (52.6% in South Africa, 37.7% in Republic of Congo, 28.2% in Swaziland, 27.4% in Cote d'Ivoire, 26.9% in Ghana, and 22.6% in Uganda). In Cote d'Ivoire and South Africa, 68.9% and 68.7% of student cigarette smokers, respectively, were not refused the sale of cigarettes because of age. The percentage of students who were offered free cigarettes by a tobacco company representative ranged from 4.7% in Cote d'Ivoire to 12.1% in South Africa. CONCLUSIONS: The method of obtaining cigarettes and access to cigarettes among students varies among sub-Saharan African countries. Adopting and enforcing interventions that prevent youth from accessing tobacco products could be an effective strategy for reducing smoking initiation among youth in sub-Saharan African countries. PMID- 26845375 TI - Online smoking cessation program for Korean Americans: Randomized trial to test effects of incentives for program completion and interim surveys. AB - INTRODUCTION: Smoking is prevalent among Korean American men. Quitting is Winning, an Internet-based, cognitive-behavioral smoking cessation program, was developed using community-based participatory research principles. METHODS: A randomized controlled trial was used to evaluate whether participants were more likely to complete the program and quit smoking at 6-months of follow-up with additional reinforcement. The main outcomes were the proportion of participants who completed the online program and the proportion who quit smoking for at least 30days, 26weeks after enrollment, among those randomized into the high reinforcement (HR) condition compared with those in the low-reinforcement (LR) condition. RESULTS: The study achieved a final enrollment of 403 participants including 56 women. Program completion was greater for the HR as compared to the LR condition (17% vs. 10%, p=.035). There was no significant difference in 30-day smoking cessation (intent-to-treat [ITT]) between the HR and LR conditions (9% vs. 8%, ns). Smoking cessation was greater among program completers as compared to those who did not complete the program (28% vs. 5%, p<.001). CONCLUSIONS: The addition of interim surveys and financial incentives for interim survey completion and program completion significantly increased the likelihood of program completion. Moreover, program completers were significantly more likely to quit smoking. Although smoking cessation rates did not significantly differ between the HR and LR conditions, the results suggest that future studies should explore the efficacy of larger financial incentives for program completion (Clinical Trial #NCT02584127). PMID- 26845376 TI - Biocontrol of fouling pests: Effect of diversity, identity and density of control agents. AB - Augmentative biocontrol, using native natural enemies, has been suggested as a promising tool to control marine biofouling pests on artificial structures. However, there are still important knowledge gaps to be addressed before biocontrol can be considered as a management tool. In a field experiment on floating marine structures we examined intra- and interspecific consumer interactions among biocontrol agents on different surface orientations. We tested the effect of identity, density and diversity of three invertebrates (the 11-arm seastar Coscinasterias muricata, the sea urchin Evechinus chloroticus and the gastropod Cook's turban Cookia sulcata) to reduce established biofouling and to prevent fouling growth on defouled surfaces. High densities of biocontrol agents were not more effective at fouling control (cover and biomass) than low densities. Nor did multi-species treatments function more effectively than mono specific ones. However, biocontrol agent identity was important, with the 11-arm seastar and Cook's turban being the most effective at fouling reduction and prevention, respectively. Surface orientation had a strong effect on the effectiveness of control agents, with the best results obtained on vertical compared to diagonal and underside surfaces. This study confirmed the potential of biocontrol as a management tool for marine pest, indicating that identity is more important than richness and density of control agents. It also highlighted the limitations of this approach on diagonal and underside surfaces, where control agents have limited retention ability. PMID- 26845377 TI - Functions of flavonoids in the central nervous system: Astrocytes as targets for natural compounds. AB - In the last decade, there have been major advances in the understanding of the role of glial cells as key elements in the formation, maintenance and refinement of synapses. Recently, the discovery of natural compounds capable of modulating nervous system function has revealed new perspectives on the restoration of the injured brain. Among these compounds, flavonoids stand out as molecules easily obtainable in the diet that have remarkable effects on cognitive performance and behavior. Nevertheless, little is known about the cellular and molecular mechanisms underlying the actions of flavonoids in the nervous system. The present review presents recent advances in the effects of natural compounds, particularly flavonoids, in the nervous system. We shed light on astrocytes as targets of flavonoids and discuss how this interaction might contribute to the effects of flavonoids on neuronal survival, differentiation and function. Finally, we discuss how the effects of flavonoids on astrocytes might contribute to the development of alternative therapeutic approaches to the treatment of neural diseases. PMID- 26845378 TI - From facilitation to competition: temperature-driven shift in dominant plant interactions affects population dynamics in seminatural grasslands. AB - Biotic interactions are often ignored in assessments of climate change impacts. However, climate-related changes in species interactions, often mediated through increased dominance of certain species or functional groups, may have important implications for how species respond to climate warming and altered precipitation patterns. We examined how a dominant plant functional group affected the population dynamics of four co-occurring forb species by experimentally removing graminoids in seminatural grasslands. Specifically, we explored how the interaction between dominants and subordinates varied with climate by replicating the removal experiment across a climate grid consisting of 12 field sites spanning broad-scale temperature and precipitation gradients in southern Norway. Biotic interactions affected population growth rates of all study species, and the net outcome of interactions between dominants and subordinates switched from facilitation to competition with increasing temperature along the temperature gradient. The impacts of competitive interactions on subordinates in the warmer sites could primarily be attributed to reduced plant survival. Whereas the response to dominant removal varied with temperature, there was no overall effect of precipitation on the balance between competition and facilitation. Our findings suggest that global warming may increase the relative importance of competitive interactions in seminatural grasslands across a wide range of precipitation levels, thereby favouring highly competitive dominant species over subordinate species. As a result, seminatural grasslands may become increasingly dependent on disturbance (i.e. traditional management such as grazing and mowing) to maintain viable populations of subordinate species and thereby biodiversity under future climates. Our study highlights the importance of population-level studies replicated under different climatic conditions for understanding the underlying mechanisms of climate change impacts on plants. PMID- 26845380 TI - Chebyshev Expansion Applied to Dissipative Quantum Systems. AB - To determine the dynamics of a molecular aggregate under the influence of a strongly time-dependent perturbation within a dissipative environment is still, in general, a challenge. The time-dependent perturbation might be, for example, due to external fields or explicitly treated fluctuations within the environment. Methods to calculate the dynamics in these cases do exist though some of these approaches assume that the corresponding correlation functions can be written as a weighted sum of exponentials. One such theory is the hierarchical equations of motion approach. If the environment, however, is described by a complex spectral density or if its temperature is low, these approaches become very inefficient. Therefore, we propose a scheme based on a Chebyshev decomposition of the bath correlation functions and detail the respective quantum master equations within second-order perturbation theory in the environmental coupling. Similar approaches have recently been proposed for systems coupled to Fermionic reservoirs. The proposed scheme is tested for a simple two-level system and compared to existing results. Furthermore, the advantages and disadvantages of the present Chebyshev approach are discussed. PMID- 26845382 TI - Diamagnetic Raman Optical Activity of Chlorine, Bromine, and Iodine Gases. AB - Magnetic Raman optical activity of gases provides unique information about their electric and magnetic properties. Magnetic Raman optical activity has recently been observed in a paramagnetic gas (Angew. Chem. Int. Ed. 2012, 51, 11058; Angew. Chem. 2012, 124, 11220). In diamagnetic molecules, it has been considered too weak to be measurable. However, in chlorine, bromine and iodine vapors, we could detect a significant signal as well. Zeeman splitting of electronic ground state energy levels cannot rationalize the observed circular intensity difference (CID) values of about 10(-4). These are explicable by participation of paramagnetic excited electronic states. Then a simple model including one electronic excited state provides reasonable spectral intensities. The results suggest that this kind of scattering by diamagnetic molecules is a general event observable under resonance conditions. The phenomenon sheds new light on the role of excited states in the Raman scattering, and may be used to probe molecular geometry and electronic structure. PMID- 26845383 TI - Pillar[5]arene-Based Glycoclusters: Synthesis and Multivalent Binding to Pathogenic Bacterial Lectins. AB - The synthesis of pillar[5]arene-based glycoclusters has been readily achieved by CuAAC conjugations of azido- and alkyne-functionalized precursors. The lectin binding properties of the resulting glycosylated multivalent ligands have been studied by at least two complementary techniques to provide a good understanding. Three lectins were selected from bacterial pathogens based on their potential therapeutic applications as anti-adhesives, namely LecA and LecB from Pseudomonas aeruginosa and BambL from Burkholderia ambifaria. As a general trend, multivalency improved the binding to lectins and a higher affinity can be obtained by increasing to a certain limit the length of the spacer arm between the carbohydrate subunits and the central macrocyclic core. PMID- 26845384 TI - Routine biliary cannulation techniques. PMID- 26845379 TI - Expression of gp120 in mice evokes anxiety behavior: Co-occurrence with increased dendritic spines and brain-derived neurotrophic factor in the amygdala. AB - Human immunodeficiency virus type 1 (HIV) infection of the brain produces cognitive and motor disorders. In addition, HIV positive individuals exhibit behavioral alterations, such as apathy, and a decrease in spontaneity or emotional responses, typically seen in anxiety disorders. Anxiety can lead to psychological stress, which has been shown to influence HIV disease progression. These considerations underscore the importance of determining if anxiety in HIV is purely psychosocial, or if by contrast, there are the molecular cascades associated directly with HIV infection that may mediate anxiety. The present study had two goals: (1) to determine if chronic exposure to viral proteins would induce anxiety-like behavior in an animal model and (2) to determine if this exposure results in anatomical abnormalities that could explain increased anxiety. We have used gp120 transgenic mice, which display behavior and molecular deficiencies similar to HIV positive subjects with cognitive and motor impairments. In comparison to wild type mice, 6 months old gp120 transgenic mice demonstrated an anxiety like behavior measured by open field, light/dark transition task, and prepulse inhibition tests. Moreover, gp120 transgenic mice have an increased number of spines in the amygdala, as well as higher levels of brain-derived neurotrophic factor and tissue plasminogen activator when compared to age-matched wild type. Our data support the hypothesis that HIV, through gp120, may cause structural changes in the amygdala that lead to maladaptive responses to anxiety. PMID- 26845385 TI - Vigilant care: An integrative reformulation regarding parental monitoring. AB - Parental monitoring was once considered to be the approved way for preventing risk behaviors by children and adolescents. In the last years, however, the concept has been the target of cogent criticism questioning the interpretation of findings which support the traditional view of monitoring. After reviewing the various criticisms and the resulting fragmentation of theory and practice, we propose the model of vigilant care as an integrative solution. Vigilant care is a flexible framework within which parents adjust their level of involvement to the warning signals they detect. By justifying moves to higher levels of vigilance with safety considerations and expressing their duty to do so in a decided but noncontrolling manner, parents legitimize their increased involvement both to the child and to themselves. The model offers a unified solution to the ongoing controversy and generates theoretical hypotheses as well as a practice-oriented research program. PMID- 26845386 TI - Antibody-Mediated Rejection in Lung Transplantation: Clinical Outcomes and Donor Specific Antibody Characteristics. AB - In the context of lung transplant (LT), because of diagnostic difficulties, antibody-mediated rejection (AMR) remains a matter of debate. We retrospectively analyzed an LT cohort at Foch Hospital to demonstrate the impact of AMR on LT prognosis. AMR diagnosis requires association of clinical symptoms, donor specific antibodies (DSAs), and C4d(+) staining and/or histological patterns consistent with AMR. Prospective categorization split patients into four groups: (i) DSA positive, AMR positive (DSA(pos) AMR(pos) ); (ii) DSA positive, AMR negative (DSA(pos) AMR(neg) ); (iii) DSA limited, AMR negative (DSA(Lim) ; equal to one specificity, with mean fluorescence intensity of 500-1000 once); and (iv) DSA negative, AMR negative (DSA(neg) ). AMR treatment consisted of a combination of plasmapheresis, intravenous immunoglobulin and rituximab. Among 206 transplanted patients, 10.7% were DSA(pos) AMR(pos) (n = 22), 40.3% were DSA(pos) AMR(neg) (n = 84), 6% were DSA(Lim) (n = 13) and 43% were DSA(neg) (n = 88). Analysis of acute cellular rejection at month 12 showed higher cumulative numbers (mean plus or minus standard deviation) in the DSA(pos) AMR(pos) group (2.1 +/- 1.7) compared with DSA(pos) AMR(neg) (1 +/- 1.2), DSA(Lim) (0.75 +/- 1), and DSA(neg) (0.7 +/- 1.23) groups. Multivariate analysis demonstrated AMR as a risk factor for chronic lung allograft dysfunction (hazard ratio [HR] 8.7) and graft loss (HR 7.56) for DSA(pos) AMR(pos) patients. Our results show a negative impact of AMR on LT clinical course and advocate for an early active diagnostic approach and evaluation of therapeutic strategies to improve prognosis. PMID- 26845387 TI - Generic applications of (13) C-detected NMR diffusion to formulated systems with suppression of thermal convection induced by proton decoupling. AB - Fast and effective structural/compositional analysis on formulated systems represents one of the major challenges encountered in analytical science. (13) C detected diffusion represents a promising tool to tackle the aforementioned challenges, particularly in industry. Toward exploring the generic applications of (13) C-detected diffusion, thermal convection induced by (1) H decoupling has been identified as a key factor that resulted in significantly reduced resolution in the diffusion dimension. Optimization of experimental parameters and utilization of double-stimulated echo-based pulse sequence both can effectively suppress the thermal convection caused by the (1) H decoupling, the success of which allows robust and generic applications of (13) C-detected diffusion to systems from mixtures of small molecules, polymer blends, and copolymers to actual complex formulated systems. The method is particularly powerful in differentiating small molecules from polymers, polymer blends from copolymers, and end-group analysis. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26845388 TI - Notochord morphogenesis in mice: Current understanding & open questions. AB - The notochord is a structure common to all chordates, and the feature that the phylum Chordata has been named after. It is a rod-like mesodermal structure that runs the anterior-posterior length of the embryo, adjacent to the ventral neural tube. The notochord plays a critical role in embryonic tissue patterning, for example the dorsal-ventral patterning of the neural tube. The cells that will come to form the notochord are specified at gastrulation. Axial mesodermal cells arising at the anterior primitive streak migrate anteriorly as the precursors of the notochord and populate the notochordal plate. Yet, even though a lot of interest has centered on investigating the functional and structural roles of the notochord, we still have a very rudimentary understanding of notochord morphogenesis. The events driving the formation of the notochord are rapid, taking place over the period of approximately a day in mice. In this commentary, we provide an overview of our current understanding of mouse notochord morphogenesis, from the initial specification of axial mesendodermal cells at the primitive streak, the emergence of these cells at the midline on the surface of the embryo, to their submergence and organization of the stereotypically positioned notochord. We will also discuss some key open questions. Developmental Dynamics 245:547-557, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26845392 TI - Mid-Infrared Spectroscopy Platform Based on GaAs/AlGaAs Thin-Film Waveguides and Quantum Cascade Lasers. AB - The performance and versatility of GaAs/AlGaAs thin-film waveguide technology in combination with quantum cascade lasers for mid-infrared spectroscopy in comparison to conventional FTIR spectroscopy is presented. Infrared radiation is provided by a quantum cascade laser (QCL) spectrometer comprising four tunable QCLs providing a wavelength range of 5-11 MUm (1925-885 cm(-1)) within a single collimated beam. Epitaxially grown GaAs slab waveguides serve as optical transducer for tailored evanescent field absorption analysis. A modular waveguide mounting accessory specifically designed for on-chip thin-film GaAs waveguides is presented serving as a flexible analytical platform in lieu of conventional attenuated total reflection (ATR) crystals uniquely facilitating macroscopic handling and alignment of such microscopic waveguide structures in real-world application scenarios. PMID- 26845390 TI - Tools for DNA adenine methyltransferase identification analysis of nuclear organization during C. elegans development. AB - C. elegans has recently emerged as a valuable model to understand the link between nuclear organization and cell fate, by combining microscopy approaches, genome-wide mapping techniques with advanced genetics. Crucial to these analyses are techniques to determine the genome-wide interaction pattern of proteins with DNA. Chromatin immunoprecipitation has proven valuable but it requires considerable amounts of starting material. This is sometimes difficult to achieve, in particular for specific genotypes (balanced strains, different sexes, severe phenotypes...). As an alternative to ChIP, DNA adenine methyltransferase identification by sequencing (DamID-seq) was recently shown to be able to characterize binding sites in single mammalian cells. Additionally, DamID can be achieved for cell-type specific analysis by expressing Dam fusion proteins under tissue specific promoters in a controlled manner. In this report, we present a user-friendly pipeline to analyse DamID-seq data in C. elegans. Based upon this pipeline, we provide a comparative analysis of libraries generated with different starting material and discuss important library features. Moreover, we introduce an adaptation of an imaging based tool to visualize in vivo the cell-specific tridimensional binding pattern of any protein of interest. PMID- 26845389 TI - Vitamin D Concentrations and Obstructive Sleep Apnea in a Multicenter Cohort of Older Males. AB - RATIONALE: Seasonal nadirs in 25-hydroxyvitamin D (25[OH]D) concentrations overlap with increased incidence and severity of obstructive sleep apnea (OSA) in winter. We hypothesized that, because lower 25(OH)D concentrations might lead to upper airway muscle dysfunction, low 25(OH)D would be associated with higher apnea-hypopnea index (AHI), a measure of OSA severity. OBJECTIVES: To determine if lower 25(OH)D concentration is associated with greater prevalence and increased severity of OSA, independent of established OSA risk factors. METHODS: Using unconditional logistic regression, we performed a cross-sectional analysis in the Outcomes of Sleep Disorders in Older Men study, which included in-home overnight polysomnography, serum 25(OH)D measurement, and collection of demographic and comorbidity data. The primary outcome was severe sleep apnea, as defined by AHI of 30/h or more. MEASUREMENTS AND MAIN RESULTS: Among 2,827 community-dwelling, largely white (92.2%), elderly (aged 76.4 +/- 5.5 yr [mean+/ SD]) males, mean 25(OH)D concentration was 28.8 (+/-8.8) ng/ml. Subjects within the lowest quartile of 25(OH)D (6-23 ng/ml) had greater odds of severe sleep apnea in unadjusted analyses (odds ratio = 1.45; 95% confidence interval = 1.02 2.07) when compared with the highest 25(OH)D quartile (35-84 ng/ml). However, further adjustment for established OSA risk factors strongly attenuated this association (multivariable adjusted odds ratio = 1.05; 95% confidence interval = 0.72-1.52), with body mass index and neck circumference as the main confounders. There was also no evidence of an independent association between lower 25(OH)D levels and increased odds of mild (AHI = 5.0-14.9/h) or moderate (AHI = 15.0 29.9/h) sleep apnea. CONCLUSIONS: Among community-dwelling older men, the association between lower 25(OH)D and sleep apnea was largely explained by confounding by larger body mass index and neck circumference. PMID- 26845393 TI - pH-Responsive Fe(III)-Gallic Acid Nanoparticles for In Vivo Photoacoustic-Imaging Guided Photothermal Therapy. AB - pH-responsive biocompatible Fe(III)-gallic acid nanoparticles with strong near infrared absorbance are very stable in mild acidic conditions, but easily decomposed in neutral conditions, which enables the nanoparticles to be stable in a tumor and easily metabolized in other organs, thus providing a safe nanoplatform for in vivo photoacoustic imaging/photothermal therapy theranostic applications. PMID- 26845394 TI - Stressors among Hispanic adults from immigrant families in the United States: Familismo as a context for ambivalence. AB - OBJECTIVES: Ongoing exposure to social stressors is widely believed to undermine the health of Hispanic immigrant families. The current work aims to explore and interpret expressions of familismo as a framework through which postimmigration experiences are interpreted and potentially given meaning. METHOD: Qualitative data were obtained from 16 focus groups in California and Massachusetts (N = 93). Fifty-two percent of the participants identified as male and 59% primarily spoke Spanish. RESULTS: Analyses revealed 3 distinct forms of ambivalence specific to familismo among Hispanic adults from immigrant families. Give and take described experiences wherein immigrants turn their backs on family in the short term to realize a better long-term future for the family. Negative change explained family misfortunes that arise in the pursuit of a better future for the family and creates doubts about the vision that motivated migration. Forced shifts suggests the navigation of daily life necessitates the inversion or abandonment of culturally idealized family roles and responsibilities. CONCLUSION: Hispanic adults from immigrant families described several situations in which competing views of familismo likely influenced the interpretation of unanticipated stressors. (PsycINFO Database Record PMID- 26845395 TI - Biomass-Swelling Assisted Synthesis of Hierarchical Porous Carbon Fibers for Supercapacitor Electrodes. AB - The preparation of porous materials from renewable energy sources is attracting intensive attention due to in terms of the application/economic advantage, and pore structural design is core in the development of efficient supercapacitors or available porous media. In this work, we focused on the transformation of natural biomass, such as cotton, into more stable porous carbonaceous forms for energy storage in practical applications. Biomorphic cotton fibers are pretreated under the effect of NaOH/urea swelling on cellulose and are subsequently used as a biomass carbon source to mold the porous microtubule structure through a certain degree of calcining. As a merit of its favorable structural features, the hierarchical porous carbon fibers exhibit an enhanced electric double layer capacitance (221.7 F g-1 at 0.3 A g-1) and excellent cycling stability (only 4.6% loss was observed after 6000 cycles at 2 A g-1). A detailed investigation displays that biomass-swelling behavior plays a significant role, not only in improving the surface chemical characteristics of biomorphic cotton fibers but also in facilitating the formation of a hierarchical porous carbon fiber structure. In contrast to traditional methods, nickel foams have been used as the collector for supercapacitor that requiring no additional polymeric binders or carbon black as support or conductive materials. Because of the absence of additive materials, we can further enhance capacitance. This remarkable capacitive performance can be due to sufficient void space within the porous microstructure. By effectively increasing the contact area between the carbon surface and the electrolyte, which can reduce the ion diffusion pathway or buffer the volume change during cycling. This approach opens a novel route to produce the abundantly different morphology of porous biomass-based carbon materials and proposes a green alternative method to meet sustainable development needs. PMID- 26845396 TI - Physical Properties, Exciton Analysis, and Visualization of Core-Excited States: An Intermediate State Representation Approach. AB - The theoretical simulation of X-ray absorption spectra is in general a challenging task. However, for small and medium-sized organic molecules, the algebraic diagrammatic construction scheme (ADC) for the polarization operator in combination with the core-valence separation approximation (CVS) has proven to yield core-excitation energies and transition moments with almost quantitative accuracy allowing for reliable construction of X-ray absorption spectra. Still, to understand core-excitation processes in detail, it is not sufficient to only compute energies, but also properties like static dipole moments and state densities are important as they provide deeper insight into the nature of core excited states. Here, we present for the first time an implementation of the intermediate state representation (ISR) approach in combination with the CVS approximation (CVS-ISR), which gives, in combination with the CVS-ADC method, direct access to core-excited state properties. The performance of the CVS ADC/CVS-ISR approach is demonstrated by means of small- and medium-sized organic molecules. Besides the calculation of core-excited state dipole moments, advanced analyses of core-excited state densities are performed using descriptors like exciton sizes and distances. Plotting electron and hole densities helps to determine the character of the state, and in particular, the investigation of detachment/attachment densities provides information about orbital relaxation effects that are crucial for understanding core excitations. PMID- 26845397 TI - Big Data: Challenges and opportunities for clinical pharmacology. PMID- 26845398 TI - Thiol-Mediated Controlled Ring-Opening Polymerization of Cysteine-Derived beta Thiolactone and Unique Features of Product Polythioester. AB - The controlled ring-opening polymerization of the beta-thiolactone derived from N Boc cysteine was achieved using N-Boc-L-cysteine methyl ester as the initiator in NMP at room temperature. The propagating end is the thiol group, which attacks the carbonyl to open the monomer ring by the C(?O)-S bond scission. A thiol-ene click reaction demonstrated the utility of the thiol group at the propagating terminal. The block copolymer was efficiently produced by the terminal coupling of the polythioester with the norbornene terminated PEG. As another interesting reaction, the polythioester underwent the main chain transformation to polycysteine through the intramolecular S-to-N acyl migration, triggered by the deprotection of the pendant Boc groups. The polythioester from L-cysteine showed Cotton effects between 200 and 300 nm in the circular dichroism (CD) spectrum. Although the CD pattern resembled that produced by the alpha-helix of polypeptide, it was ascribable not to the second structure but to the relative orientation of the thioester and carbamate carbonyls in the repeating unit. PMID- 26845399 TI - A windfall for US biomedical science. PMID- 26845400 TI - An eye to the future: Researchers debate best path for stem cell-derived therapies. PMID- 26845402 TI - Mutations as munitions: Neoantigen vaccines get a closer look as cancer treatment. PMID- 26845403 TI - Targeted stimulation of the spinal cord to restore locomotor activity. PMID- 26845404 TI - Oxidation and mitochondrial origin of NET DNA in the pathogenesis of lupus. PMID- 26845406 TI - Erratum: Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease. PMID- 26845407 TI - Erratum: Cardiac RKIP induces a beneficial beta-adrenoceptor-dependent positive inotropy. PMID- 26845409 TI - Erratum: Genomic landscape of carcinogen-induced and genetically induced mouse skin squamous cell carcinoma. PMID- 26845408 TI - Corrigendum: KLF4-dependent phenotypic modulation of smooth muscle cells has a key role in atherosclerotic plaque pathogenesis. PMID- 26845405 TI - Targeting EZH2 in cancer. AB - Recent genomic studies have resulted in an emerging understanding of the role of chromatin regulators in the development of cancer. EZH2, a histone methyl transferase subunit of a Polycomb repressor complex, is recurrently mutated in several forms of cancer and is highly expressed in numerous others. Notably, both gain-of-function and loss-of-function mutations occur in cancers but are associated with distinct cancer types. Here we review the spectrum of EZH2 associated mutations, discuss the mechanisms underlying EZH2 function, and synthesize a unifying perspective that the promotion of cancer arises from disruption of the role of EZH2 as a master regulator of transcription. We further discuss EZH2 inhibitors that are now showing early signs of promise in clinical trials and also additional strategies to combat roles of EZH2 in cancer. PMID- 26845410 TI - Corrigendum: Metformin activates a duodenal Ampk-dependent pathway to lower hepatic glucose production in rats. PMID- 26845411 TI - Heteroanionic Materials Based on Copper Clusters, Bisphosphonates, and Polyoxometalates: Magnetic Properties and Comparative Electrocatalytic NO(x) Reduction Studies. AB - Three compounds associating for the first time polyoxotungstates, bisphosphonates, and copper ions were structurally characterized. They consist in heteropolyanionic monodimensional materials where [Cu6(Ale)4(H2O)4](4-) (Ale = alendronate = [O3PC(O)(C3H6NH3)PO3](4-)) complexes alternate with polyoxometalate (POM) units. In Na12[{SiW9O34Cu3(Ale)(H2O)}{Cu6(Ale)4(H2O)4}].50H2O (SiW9CuAle), the polyoxometalate core consists in a {SiW9Cu3} monomer capped by a pentacoordinated Ale ligand, while sandwich-type Keggin {(SbW9O33)2Cu3(H2O)(2.5)Cl(0.5)} and Dawson {(P2W15O56)2Cu4(H2O)2} complexes are found in Na8Li29[{(SbW9O33)2Cu3(H2O)(2.5)Cl(0.5)}2{Cu6(Ale)4(H2O)4}3].163H2O (SbW9CuAle) and Na20[{(P2W15O56)2Cu4(H2O)2}{Cu6(Ale)4(H2O)4}].50H2O (P2W15CuAle), respectively. A comparative magnetic study of the SiW9CuAle and SbW9CuAle compounds enabled full quantification of the Cu(II) superexchange interactions both for the POM and non-POM subunits, evidencing that, while the paramagnetic centers are anti-ferromagnetically coupled in the polyoxometalate units, both anti-ferromagnetic and ferromagnetic interactions coexist in the {Cu6(Ale)4(H2O)4} cluster. All the studied compounds present a good efficiency upon the reduction of HNO2 or NO2(-), the POM acting as a catalyst. However, it has been found that SbW9CuAle is inactive toward the reduction of nitrates, highlighting that both the {(SbW9O33)2Cu3} unit and the {Cu6(Ale)4(H2O)4} cluster do not act as electrocatalysts for this reaction. In contrast, SiW9CuAle and P2W15CuAle have shown a significant activity upon the reduction of NO3(-) and thus both at pH 1 and pH 5, evidencing that the chemical nature of the polyoxometalate is a crucial parameter even if it acts as precatalyst. Moreover, comparison of the activities of P2W15CuAle and [(P2W15O56)2Cu4(H2O)2](16-) evidenced that if the [Cu6(Ale)4(H2O)4](4-) cluster does not act as electrocatalyst, it acts as a cofactor, significantly enhancing the catalytic efficiency of the active POM. PMID- 26845412 TI - Inflammatory fibroid polyp (Vanek's tumor) of the gastric antrum: is treatment always mandatory? AB - INTRODUCTION: Inflammatory fibroid polyp (IFP), also known as Vanek's tumor, is a rare polypoid lesion of the gastrointestinal tract. A recently observed case led us to review the literature, with the aim to discuss the management of asymptomatic gastric IFPs. CASE REPORT: A 71-year-old man was endoscopically diagnosed as having a polypoid lesion located in the gastric antrum. Histopathological and himmunoistochemical studies of endoscopic biopsies revealed an IFP. Endoscopic resection was proposed, but the patient refused such a treatment because he was asymptomatic for his polyp. After three years the patient is asymptomatic and the endoscopic surveillance follow-up has showed no evidence of growth nor other modifications of the gastric IFP. DISCUSSION: Gastric IFPs are benign polyps of unknown etiology which sometimes pose problems of differential diagnosis with GISTs, and various mesenchymal tumors. Although gastric IFPs are benign lesions usually asymptomatic, most of the cases reported in the literature have been treated by endoscopic or surgical excision. In the case described herein, no modifications of the polyp were observed at endoscopic follow-up. CONCLUSION: This case description suggests that removal of gastric IFPs, either by endoscopic or surgical approach, may not be mandatory in asymptomatic patients. KEY WORDS: Inflammatory Fibroid Polyp, Stomach, Vanek's tumor. PMID- 26845413 TI - Leveraging Large-scale Behavioral Profiling in Zebrafish to Explore Neuroactive Polypharmacology. AB - Many psychiatric drugs modulate the nervous system through multitarget mechanisms. However, systematic identification of multitarget compounds has been difficult using traditional in vitro screening assays. New approaches to phenotypic profiling in zebrafish can help researchers identify novel compounds with complex polypharmacology. For example, large-scale behavior-based chemical screens can rapidly identify large numbers of structurally diverse and phenotype related compounds. Once these compounds have been identified, a systems-level analysis of their structures may help to identify statistically enriched target pathways. Together, systematic behavioral profiling and multitarget predictions may help researchers identify new behavior-modifying pathways and CNS therapeutics. PMID- 26845414 TI - Controlling Self-Assembly Kinetics of DNA-Functionalized Liposomes Using Toehold Exchange Mechanism. AB - The selectivity of Watson-Crick base pairing has allowed the design of DNA-based functional materials bearing an unprecedented level of accuracy. Examples include DNA origami, made of tiles assembling into arbitrarily complex shapes, and DNA coated particles featuring rich phase behaviors. Frequently, the realization of conceptual DNA-nanotechnology designs has been hampered by the lack of strategies for effectively controlling relaxations. In this article, we address the problem of kinetic control on DNA-mediated interactions between Brownian objects. We design a kinetic pathway based on toehold-exchange mechanisms that enables rearrangement of DNA bonds without the need for thermal denaturation, and test it on suspensions of DNA-functionalized liposomes, demonstrating tunability of aggregation rates over more than 1 order of magnitude. While the possibility to design complex phase behaviors using DNA as a glue is already well recognized, our results demonstrate control also over the kinetics of such systems. PMID- 26845415 TI - GNPAT variant is associated with iron phenotype in healthy Taiwanese women: A population without the HFE C282Y mutation. PMID- 26845416 TI - Carnosic acid attenuates acute ethanol-induced liver injury via a SIRT1/p66Shc mediated mitochondrial pathway. AB - Ethanol-induced liver injury is associated with oxidative stress and hepatocyte apoptosis. We previously demonstrated that SIRT1/p66Shc pathway activation attenuates hepatocyte apoptosis in liver ischemia/reperfusion. The current study aimed to investigate whether carnosic acid (CA), a natural antioxidant, can inhibit acute ethanol-induced apoptosis of hepatocytes and to determine the effect of SIRT1/p66Shc on this process. Our results showed that CA pretreatment significantly reduced ethanol-induced histologic damage, serum aminotransferase activity, and oxidative stress in rats. Importantly, CA pretreatment increased SIRT1 expression following ethanol exposure. Furthermore, p66Shc expression was negatively correlated with SIRT1 expression. Consistent with the results demonstrating p66Shc inhibition, CA pretreatment inhibited the release of cytochrome C and apoptosis-inducing factor (AIF) from mitochondria. After exposing L02 cells to ethanol, the increased SIRT1 expression induced by CA was abrogated by pharmacologic SIRT1 inhibition or the use of siRNA against SIRT1. Additionally, SIRT1 inhibition significantly abrogated the suppression of p66Shc expression and mitochondrial translocation induced by CA. Accordingly, CA-induced decreases in the release of cytochrome C and AIF and in mitochondrial apoptosis were nearly abolished by SIRT1 knockdown. These data indicated that CA-activated SIRT1 is protective against ethanol treatment. In summary, CA attenuates acute ethanol-induced liver injury via a SIRT1/p66Shc-mediated mitochondrial pathway. PMID- 26845417 TI - Advisory Committee on Immunization Practices Recommended Immunization Schedule for Adults Aged 19 Years or Older--United States, 2016. AB - In October 2015, the Advisory Committee on Immunization Practices (ACIP)* approved the Recommended Immunization Schedule for Adults Aged 19 Years or Older, United States, 2016. This schedule provides a summary of ACIP recommendations for the use of vaccines routinely recommended for adults aged 19 years or older in two figures, footnotes for each vaccine, and a table that describes primary contraindications and precautions for commonly used vaccines for adults. Although the figures in the adult immunization schedule illustrate recommended vaccinations that begin at age 19 years, the footnotes contain information on vaccines that are recommended for adults that may begin at age younger than age 19 years. The footnotes also contain vaccine dosing, intervals between doses, and other important information and should be read with the figures. PMID- 26845418 TI - Unveiling in Vivo Subcutaneous Thermal Dynamics by Infrared Luminescent Nanothermometers. AB - The recent development of core/shell engineering of rare earth doped luminescent nanoparticles has ushered a new era in fluorescence thermal biosensing, allowing for the performance of minimally invasive experiments, not only in living cells but also in more challenging small animal models. Here, the potential use of active-core/active-shell Nd(3+)- and Yb(3+)-doped nanoparticles as subcutaneous thermal probes has been evaluated. These temperature nanoprobes operate in the infrared transparency window of biological tissues, enabling deep temperature sensing into animal bodies thanks to the temperature dependence of their emission spectra that leads to a ratiometric temperature readout. The ability of active core/active-shell Nd(3+)- and Yb(3+)-doped nanoparticles for unveiling fundamental tissue properties in in vivo conditions was demonstrated by subcutaneous thermal relaxation monitoring through the injected core/shell nanoparticles. The reported results evidence the potential of infrared luminescence nanothermometry as a diagnosis tool at the small animal level. PMID- 26845419 TI - Reducing Pediatric Readmissions: Using a Discharge Bundle Combined With Teach back Methodology. AB - The authors describe a quality improvement initiative aimed at decreasing unplanned 7- and 30-day readmission rates in an urban, pediatric, tertiary care hospital. A stepwise approach was used to disseminate the pilot initiative across 16 inpatient units. Use of a teach-back methodology combined with a discharge bundle resulted in an 8% reduction in 7-day readmission and 10% reduction in 30 day readmission over 16 months. PMID- 26845420 TI - Standardizing Handoff Communication: Content Analysis of 27 Handoff Mnemonics. AB - This study synthesizes information contained in 27 mnemonics to identify what information should be communicated during a handoff. Clustering and content analysis resulted in 12 primary information clusters that should be communicated. Given the large amount of information identified, it would be beneficial to use a structured handoff communication tool developed using a participatory approach. In addition, we recommend local standardization of information communicated during handoffs with variation across settings. PMID- 26845421 TI - No-Pass Zone: Multidisciplinary Approach to Responding to Patient Needs. AB - A nurse's need to juggle multiple priorities often leads to delays in responses to patient call lights, which may result in the patient's needs not being met quickly. Low patient satisfaction scores related to hospital staff responding to patient needs created urgency for this system to implement the No-Pass Zone, a multidisciplinary team approach to responding to call lights. A successful implementation of this intervention resulted in patients' needs being met more quickly as indicated by improved Hospital Consumer Assessment of Health Care Providers and Systems performance postimplementation. PMID- 26845422 TI - Transformational Teamwork: Exploring the Impact of Nursing Teamwork on Nurse Sensitive Quality Indicators. AB - The purpose of this research was to investigate the relationship between nursing teamwork and NDNQI outcomes including pressure ulcers, falls, and catheter associated urinary tract infections. Correlational analysis resulted in statistically significant relationships. Improving teamwork in medical-surgical acute care units can transform care and impact the occurrence of preventable adverse outcomes. PMID- 26845423 TI - Oxidatively-induced aromatic cyanation mediated by Ni(iii). AB - A Ni(ii) complex with two t-butylisocyanide ligands supported by a N3C(-) type tetradentate ligand was synthesized and characterized. Quantitative generation of the aromatic cyanation product, (tBu)N3C-CN, is observed by reacting this Ni(ii) complex with 1 equiv. of an oxidant. Reactivity studies suggest that this oxidatively-induced cyanation involves a heterolytic cleavage of the N-(t)Bu bond and is mediated by Ni(iii). PMID- 26845424 TI - Marital Status and Frailty in Older People: Gender Differences in the Progetto Veneto Anziani Longitudinal Study. AB - OBJECTIVES: Marital status has been associated with disability and mortality, but its potential role as a factor influencing frailty has yet to be thoroughly investigated. The analysis of gender-related differences in the relationship between marital status and frailty is another interesting matter that remains to be fully elucidated. The aim of our study was to examine the association between marital status and the incidence of frailty in a cohort of older men and women over a 4.4-year follow-up. MATERIALS AND METHODS: A sample of 1887 subjects older than 65 years, enrolled under the Progetto Veneto Anziani (Pro.V.A.) and with no evidence of frailty at baseline, were grouped by marital status. The incidence of frailty after 4.4 years was measured as the presence of at least three of the Fried criteria. RESULTS: After the follow-up period, 414 (21.9%) new cases of frailty were identified. Multivariate logistic regression models demonstrated that male gender carried a higher risk of developing frailty among men who had never married (odds ratio [OR] = 3.84, 95% confidence interval [95% CI] = 2.76 5.35; p < 0.0001) and were widowed (OR = 1.43, 95% CI = 1.06-1.95, p = 0.02) than among married participants. For female gender, widows had significantly lower odds of becoming frail than married women (OR = 0.77, 95% CI = 0.66-0.91, p = 0.002). The determinants of frailty more influenced by marital status were unintentional weight loss, low daily energy expenditure, and exhaustion. CONCLUSIONS: Marital status seems to significantly influence the onset of frailty, with some gender-specific differences. Unmarried men were at higher risk of frailty, while widowed women carried a lower risk of becoming frail than married women. PMID- 26845426 TI - Sequential bacillus Calmette-Guerin/Electromotive Drug Administration of Mitomycin C as the Standard Intravesical Regimen in High Risk Nonmuscle Invasive Bladder Cancer: 2-Year Outcomes. AB - PURPOSE: Sequential bacillus Calmette-Guerin/electromotive drug administration of mitomycin C is reported to be superior to bacillus Calmette-Guerin alone but it has not been widely adopted. We aimed to determine the efficacy and tolerability of sequential bacillus Calmette-Guerin/electromotive drug administration of mitomycin C in high risk, nonmuscle invasive bladder cancer. MATERIALS AND METHODS: Starting in 2009 bacillus Calmette-Guerin/electromotive drug administration of mitomycin C was introduced as the standard induction regime in patients with high risk, nonmuscle invasive bladder cancer undergoing bladder conservation. As induction bacillus Calmette-Guerin was administered in weeks 1 and 2. Mitomycin C was administered in electromotive fashion (40 mg and 20 mA current for 30 minutes) in week 3 and repeated thrice for a total of 9 weeks. As maintenance 3 doses of bacillus Calmette-Guerin were given 3 months after induction and then every 6 months for 3 years. Outcome measures were disease recurrence at first check, 1 and 2-year cystoscopy, and treatment tolerability. RESULTS: Of the 151 patients with high risk, nonmuscle invasive bladder cancer treated between June 2009 and 2013, 44 underwent primary cystectomy and 107 received sequential bacillus Calmette-Guerin/electromotive drug administration of mitomycin C. Disease was high grade Ta/T1 in 86 patients (80%), of whom 34 (32%) also had carcinoma in situ. A total of 19 patients (18%) had primary carcinoma in situ and 2 had recurrent large volume, low grade disease. Of 107 patients 104 underwent first check cystoscopy, including 90 (87%) who were clear. Of the 90 complete responders 86 underwent 1-year cystoscopy, including 74 (86%) who were recurrence-free. Of the 74 patients 71 underwent 2-year cystoscopy, of whom 66 (93%) remained recurrence-free. The full induction schedule was not completed in 30 patients (28%), including 16 and 14 with minor and major schedule alterations, respectively. There was no difference in recurrence between patients who received a full vs a reduced induction schedule. CONCLUSIONS: This study confirms the excellent oncologic efficacy of sequential bacillus Calmette-Guerin/electromotive drug administration of mitomycin C in cases of high risk, nonmuscle invasive bladder cancer. Tolerability is a challenge but alterations to the 9-week schedule appeared to have a negligible impact on outcomes. PMID- 26845425 TI - Intraoperative Combined Use of Somatosensory Evoked Potential, Microvascular Doppler Sonography, and Indocyanine Green Angiography in Clipping of Intracranial Aneurysm. AB - BACKGROUND The aim of this study was to evaluate the effect of combining application of somatosensory evoked potential (SEP), microvascular Doppler sonography (MDS), and indocyanine green angiography (ICGA) in intracranial aneurysm clipping surgery. MATERIAL AND METHODS A total of 158 patients undergoing an intracranial aneurysm clipping operation were recruited. All patients were evaluated with intraoperative SEP and MDS monitoring, and 28 of them were evaluated with intraoperative combined monitoring of SEP, MDS, and ICGA. RESULTS The SEP waves dropped during temporary occlusion of arteries in 19 cases (12.0%), and returned to normal after the clips were repositioned. After aneurysms were clipped, the vortex flow signals were detected by MDS in 6 cases. The aneurysm neck remnants were detected by ICGA in 2 cases of olfactory artery (OA) and in 1 case of middle cerebral artery (MCA), which disappeared after the clips were repositioned. Postoperative CTA or DSA showed that aneurysms were clipped completely and parent arteries and perforating vessels were patent. GOS at 1 month after the surgery was good in 111 cases (70.3%), mild disability in 22 cases (13.9%), severe disability in 14 cases (8.9%), vegetative state in 5 cases (3.2%), and death in 6 cases (3.8%). CONCLUSIONS Intraoperative combining application of SEP, MDS, and ICGA can reduce brain tissue ischemia and damage and disability and mortality rate after effective clipping of intracranial aneurysms, thereby improving surgical outcomes. PMID- 26845427 TI - Effect of iron and carbon monoxide on fibrinogenase-like degradation of plasmatic coagulation by venoms of four Crotalus species. AB - Annually, thousands suffer poisonous snake bite, often from defibrinogenating species. Iron and carbon monoxide (CO) improve coagulation kinetics by modulation of fibrinogen as demonstrated in various Agkistrodon species and Crotalus atrox. Thus, we sought to determine whether pretreatment of plasma with iron and CO could attenuate venom-mediated catalysis of fibrinogen obtained from four common Crotalus species with known fibrinogenase activity. Human plasma was pretreated with ferric chloride (0-10 MUmol/l) and CO-releasing molecule-2 (0-100 MUmol/l) prior to exposure to venom from a Northern Pacific rattlesnake, Arizona black rattlesnake, prairie rattlesnake, or red diamond rattlesnake. The concentration of venom used decreased coagulation function of one or more kinetic parameters by at least 50% of normal values. Coagulation kinetics were determined with thrombelastography.Three snake venoms significantly degraded plasmatic coagulation kinetics, prolonging the onset to clot formation, diminishing velocity of clot growth and decreasing clot strength. However, red diamond rattlesnake venom exposure resulted in mixed coagulation kinetics, significantly decreasing the time to onset of coagulation without decreasing the velocity of clot growth. Iron and CO attenuated these coagulation kinetic changes in a species-specific manner. Further in vitro investigation of other fibrinogenolytic venoms is indicated to determine if iron and CO can attenuate venom compromised coagulation. PMID- 26845429 TI - Fullerene and corannulene derivatives acting as insulators of Cl(-) and BeH2. AB - The capacity of corannulene and its benzo-derivatives CxH10 (x = 20-60) as prototypes of non-planar pi-aromatic systems which mimic the end of carbon nanotubes to act as insulators between BeH2 and Cl(-) chemical entities has been explored by means of M06-2x/cc-pVDZ and M06-2x/6-311+G(d) calculations. For the sake of completeness, the set investigated includes also fullerene, C60. All these aromatic derivatives lead to stable binary complexes either with BeH2 or halogen (Cl(-)) anions. For BeH2, however, only the complexes in which the interaction involves the convex face of the aromatic system are stable. No significant changes are observed when the binding energies (BEs) of the BeH2 complexes are compared to those involving planar aromatic compounds, but the ones involving Cl(-) with the concave face of the aromatic moiety can be very large, because its curvature favors many contacts of the anion with the carbon atoms of the pi-aromatic system. The formation of these binary complexes changes to a large extent the electrostatic potential on the free face of the aromatic system leading to a mutual reinforcement of both interactions, the beryllium bond and the interaction with Cl(-), when the ternary complexes are formed. As a result, the BEs for the triads are larger than the sum of the BEs of the corresponding binary complexes and the distances between the aromatic subunit and BeH2 or Cl(-) become shorter in the triads than in the binary complexes. A MBIE analysis also indicates that the enhanced stability of ternary complexes arises mainly from the reinforcement of the beryllium bonds as well as from the three-body terms. An exploration of all the minima for BeH2:C60H10:Cl(-) shows that BeH2 binds preferentially to the peripheral aromatic rings than those in the more curved region. PMID- 26845428 TI - Ultrasonic propulsion of kidney stones. AB - PURPOSE OF REVIEW: Ultrasonic propulsion is a novel technique that uses short bursts of focused ultrasonic pulses to reposition stones transcutaneously within the renal collecting system and ureter. The purpose of this review is to discuss the initial testing of effectiveness and safety, directions for refinement of technique and technology, and opinions on clinical application. RECENT FINDINGS: Preclinical studies with a range of probes, interfaces, and outputs have demonstrated feasibility and consistent safety of ultrasonic propulsion with room for increased outputs and refinement toward specific applications. Ultrasonic propulsion was used painlessly and without adverse events to reposition stones in 14 of 15 human study participants without restrictions on patient size, stone size, or stone location. The initial feasibility study showed applicability in a range of clinically relevant situations, including facilitating passage of residual fragments following ureteroscopy or shock wave lithotripsy, moving a large stone at the ureteropelvic junction with relief of pain, and differentiating large stones from a collection of small fragments. SUMMARY: Ultrasonic propulsion shows promise as an office-based system for transcutaneously repositioning kidney stones. Potential applications include facilitating expulsion of residual fragments following ureteroscopy or shock wave lithotripsy, repositioning stones prior to treatment, and repositioning obstructing ureteropelvic junction stones into the kidney to alleviate acute renal colic. PMID- 26845430 TI - Agkistrodon piscivorus spermatogenesis addendum: The effect of Hurricane Katrina on spermatogenesis of the western cottonmouth snake. AB - Recent studies detailed the spermatogenic cycle of the Western Cottonmouth Snake, Agkistrodon piscivorus and noted that spermatogenesis is bimodal, with active periods during March-June and August-October in southeastern Louisiana. However, only spermatogonia were present in September in the only specimen that was captured and the authors state that the individual "should have a high testis volume and also show spermiogenic activity." The specimen in their study was caught immediately following Hurricane Katrina outside of its normal habitat. Therefore, in order to verify their assumption, individuals were captured during September of 2008 and the testes were spermatogenically active with spermatogonia, spermatocytes, and mature spermatozoa being present in the seminiferous epithelium of the testes. These data indicate that Hurricane Katrina could have had an impact on the spermatogenic cycle in Cottonmouths, resulting in stress-induced testicular regression. PMID- 26845431 TI - Impact of Canopy Openness on Spider Communities: Implications for Conservation Management of Formerly Coppiced Oak Forests. AB - Traditional woodland management created a mosaic of differently aged patches providing favorable conditions for a variety of arthropods. After abandonment of historical ownership patterns and traditional management and the deliberate transformation to high forest after World War II, large forest areas became darker and more homogeneous. This had significant negative consequences for biodiversity. An important question is whether even small-scale habitat structures maintained by different levels of canopy openness in abandoned coppiced forest may constitute conditions suitable for forest as well as open habitat specialists. We investigated the effect of canopy openness in former traditionally coppiced woodlands on the species richness, functional diversity, activity density, conservation value, and degree of rareness of epigeic spiders. In each of the eight studied locations, 60-m-long transect was established consisting of five pitfall traps placed at regular 15 m intervals along the gradient. Spiders were collected from May to July 2012. We recorded 90 spider species, including high proportions of xeric specialists (40%) and red-listed threatened species (26%). The peaks of conservation indicators, as well as spider community abundance, were shifted toward more open canopies. On the other hand, functional diversity peaked at more closed canopies followed by a rapid decrease with increasing canopy openness. Species richness was highest in the middle of the canopy openness gradient, suggesting an ecotone effect. Ordinations revealed that species of conservation concern tended to be associated with sparse and partly opened canopy. The results show that the various components of biodiversity peaked at different levels of canopy openness. Therefore, the restoration and suitable forest management of such conditions will retain important diversification of habitats in formerly coppiced oak forest stands. We indicate that permanent presence of small-scale improvements could be suitable conservation tools to prevent the general decline of woodland biodiversity in the intensified landscape of Central Europe. PMID- 26845432 TI - miR-137 Suppresses the Phosphorylation of AKT and Improves the Dexamethasone Sensitivity in Multiple Myeloma Cells Via Targeting MITF. AB - BACKGROUND: Multiple myeloma (MM), a clonal B cell malignancy characterized by the proliferation of plasma cells within the bone marrow, is still an incurable disease, and therefore, finding new therapeutic targets is urgently required. Although microRNA-137 (miR-137), which is involved in a variety of cellular processes, has been reported to be under-expressed in many types of solid tumors, its role in MM is less known. METHODS: In this study, the target gene and the potential effect of miR-137 in MM were investigated. . RESULTS: The results showed significantly down regulated expression of miR-137 in MM cell lines and in the CD138+ bone marrow mononuclear cells of MM patients. A dual luciferase reporter gene analysis revealed that MITF is a direct target of miR-137. The overexpression of miR-137 or transfection of MITF-shRNA had no significant effect on the expression of serine/ threonine protein kinase (AKT), but the expression of MITF, c-MET, p-AKT, and its phosphorylated substrate protein decreased significantly, which was accompanied by an increase in p53 expression. In addition, the overexpression of miR-137 or MITF-shRNA significantly improved the 36-hour inhibition rate and apoptosis rate in multiple myeloma cells treated with dexamethasone. The overexpression of MITF could counteract the biological effect of miR-137 in multiple myeloma cells. CONCLUSION: We conclude that MITF is a direct target of miR-137. The miR-137 can improve the dexamethasone sensitivity in multiple myeloma cells by reducing the c-MET expression and further decreasing the AKT phosphorylation via targeting MITF. PMID- 26845433 TI - BRCA1-Associated Triple-Negative Breast Cancer and Potential Treatment for Ruthenium-Based Compounds. AB - Triple-negative breast cancer (TNBC) is defined by the absence of expression of estrogen receptor (ER), progesterone receptor (PR), and a lack of overexpression or amplification of human epidermal growth factor receptor 2 (HER2). The clinicopathological characteristics of TNBC include a high grading, a high rate of cell proliferation and a greater degree of chromosomal rearrangement. Patients with triple-negative breast cancer are more likely to be drug resistant and more difficult to treat, and are also frequently BRCA1 mutants. Methylation of the BRCA1 promoter region is associated with a reduction of the BRCA1 mRNA level. TNBC patients with a methylated BRCA1 had a better disease-free survival compared with those with non-methylated BRCA1. From a therapeutic perspective, the expression level of BRCA1 has been a major determinant of the responses to different classes of chemotherapy. BRCA1-dysfunctional tumors are hypersensitive to DNA damaging chemotherapeutic agents like platinum drugs. Although platinum based drugs are currently widely used as conventional chemotherapeutic drugs in breast cancer chemotherapy, their use has several disadvantages. It is therefore of interest to seek out alternative therapeutic metal-based compounds that could overcome the limitations of these platinum based drugs. Ruthenium-based compounds could be the most promising alternative to the platinum drugs. This review highlights the use of BRCA1 as a predictive marker as well as for a potential drug target for anticancer ruthenium compounds. PMID- 26845434 TI - Proteomic and Metabolic Signatures of Esophageal Squamous Cell Carcinoma. AB - Esophageal squamous cell carcinoma (ESCC), which is the most common subtype of esophageal cancers, is the sixth leading cause of cancer death worldwide with a five-year survival rate of 19%. Identification of efficient biomarkers for early detection and better understanding of the molecular mechanisms of ESCC may offer reduced mortality. However, proper biomarkers for clinical diagnosis and prognosis have not been defined yet. In the presented study, we employed a systematic and integrative 'omics' strategy to reconstruct networks of transcriptional regulation and protein-protein interaction to identify novel biomarkers, potential molecular targets, and mechanisms of transcriptional control in ESCC. Towards this end, we revealed 30 down-regulated and 21 up regulated genes as ESCC specific biomarkers since these were differentially expressed between 91 ESCC tumor samples compared to normal tissues in five different datasets. We report the association of ACPP, C2orf54, DYNLT3, ENDOU, FMO2, and KANK1 (down-regulated genes) and COL10A1, FNDC3B, HOMER3, MARCKSL1, and RFC4 (up-regulated genes) to ESCC for the first time. Further, the ESCC driven molecular pathways were also constructed to elucidate the molecular mechanism of the disease; specifically several metabolic pathways were down-regulated while the signaling pathways were up-regulated. Additionally, reporter metabolites for ESCC were analyzed and metabolic dysfunction was ascertained in arachidonic acid metabolism and steroid hormone biosynthesis pathways. The multi-omics network strategy presented here may enable discovery of novel biomarkers and targets for personalized medicine in ESCC patients. PMID- 26845435 TI - Receptive Field Vectors of Genetically-Identified Retinal Ganglion Cells Reveal Cell-Type-Dependent Visual Functions. AB - Sensory stimuli are encoded by diverse kinds of neurons but the identities of the recorded neurons that are studied are often unknown. We explored in detail the firing patterns of eight previously defined genetically-identified retinal ganglion cell (RGC) types from a single transgenic mouse line. We first introduce a new technique of deriving receptive field vectors (RFVs) which utilises a modified form of mutual information ("Quadratic Mutual Information"). We analysed the firing patterns of RGCs during presentation of short duration (~10 second) complex visual scenes (natural movies). We probed the high dimensional space formed by the visual input for a much smaller dimensional subspace of RFVs that give the most information about the response of each cell. The new technique is very efficient and fast and the derivation of novel types of RFVs formed by the natural scene visual input was possible even with limited numbers of spikes per cell. This approach enabled us to estimate the 'visual memory' of each cell type and the corresponding receptive field area by calculating Mutual Information as a function of the number of frames and radius. Finally, we made predictions of biologically relevant functions based on the RFVs of each cell type. RGC class analysis was complemented with results for the cells' response to simple visual input in the form of black and white spot stimulation, and their classification on several key physiological metrics. Thus RFVs lead to predictions of biological roles based on limited data and facilitate analysis of sensory-evoked spiking data from defined cell types. PMID- 26845436 TI - Adaptive Remodeling of the Bacterial Proteome by Specific Ribosomal Modification Regulates Pseudomonas Infection and Niche Colonisation. AB - Post-transcriptional control of protein abundance is a highly important, underexplored regulatory process by which organisms respond to their environments. Here we describe an important and previously unidentified regulatory pathway involving the ribosomal modification protein RimK, its regulator proteins RimA and RimB, and the widespread bacterial second messenger cyclic-di-GMP (cdG). Disruption of rimK affects motility and surface attachment in pathogenic and commensal Pseudomonas species, with rimK deletion significantly compromising rhizosphere colonisation by the commensal soil bacterium P. fluorescens, and plant infection by the pathogens P. syringae and P. aeruginosa. RimK functions as an ATP-dependent glutamyl ligase, adding glutamate residues to the C-terminus of ribosomal protein RpsF and inducing specific effects on both ribosome protein complement and function. Deletion of rimK in P. fluorescens leads to markedly reduced levels of multiple ribosomal proteins, and also of the key translational regulator Hfq. In turn, reduced Hfq levels induce specific downstream proteomic changes, with significant increases in multiple ABC transporters, stress response proteins and non-ribosomal peptide synthetases seen for both DeltarimK and Deltahfq mutants. The activity of RimK is itself controlled by interactions with RimA, RimB and cdG. We propose that control of RimK activity represents a novel regulatory mechanism that dynamically influences interactions between bacteria and their hosts; translating environmental pressures into dynamic ribosomal changes, and consequently to an adaptive remodeling of the bacterial proteome. PMID- 26845437 TI - Persistent Chaos of Measles Epidemics in the Prevaccination United States Caused by a Small Change in Seasonal Transmission Patterns. AB - Epidemics of infectious diseases often occur in predictable limit cycles. Theory suggests these cycles can be disrupted by high amplitude seasonal fluctuations in transmission rates, resulting in deterministic chaos. However, persistent deterministic chaos has never been observed, in part because sufficiently large oscillations in transmission rates are uncommon. Where they do occur, the resulting deep epidemic troughs break the chain of transmission, leading to epidemic extinction, even in large cities. Here we demonstrate a new path to locally persistent chaotic epidemics via subtle shifts in seasonal patterns of transmission, rather than through high-amplitude fluctuations in transmission rates. We base our analysis on a comparison of measles incidence in 80 major cities in the prevaccination era United States and United Kingdom. Unlike the regular limit cycles seen in the UK, measles cycles in US cities consistently exhibit spontaneous shifts in epidemic periodicity resulting in chaotic patterns. We show that these patterns were driven by small systematic differences between countries in the duration of the summer period of low transmission. This example demonstrates empirically that small perturbations in disease transmission patterns can fundamentally alter the regularity and spatiotemporal coherence of epidemics. PMID- 26845438 TI - A Computationally Designed Hemagglutinin Stem-Binding Protein Provides In Vivo Protection from Influenza Independent of a Host Immune Response. AB - Broadly neutralizing antibodies targeting a highly conserved region in the hemagglutinin (HA) stem protect against influenza infection. Here, we investigate the protective efficacy of a protein (HB36.6) computationally designed to bind with high affinity to the same region in the HA stem. We show that intranasal delivery of HB36.6 affords protection in mice lethally challenged with diverse strains of influenza independent of Fc-mediated effector functions or a host antiviral immune response. This designed protein prevents infection when given as a single dose of 6.0 mg/kg up to 48 hours before viral challenge and significantly reduces disease when administered as a daily therapeutic after challenge. A single dose of 10.0 mg/kg HB36.6 administered 1-day post-challenge resulted in substantially better protection than 10 doses of oseltamivir administered twice daily for 5 days. Thus, binding of HB36.6 to the influenza HA stem region alone, independent of a host response, is sufficient to reduce viral infection and replication in vivo. These studies demonstrate the potential of computationally designed binding proteins as a new class of antivirals for influenza. PMID- 26845439 TI - Reassortment of Human and Animal Rotavirus Gene Segments in Emerging DS-1-Like G1P[8] Rotavirus Strains. AB - The emergence and rapid spread of novel DS-1-like G1P[8] human rotaviruses in Japan were recently reported. More recently, such intergenogroup reassortant strains were identified in Thailand, implying the ongoing spread of unusual rotavirus strains in Asia. During rotavirus surveillance in Thailand, three DS-1 like intergenogroup reassortant strains having G3P[8] (RVA/Human-wt/THA/SKT 281/2013/G3P[8] and RVA/Human-wt/THA/SKT-289/2013/G3P[8]) and G2P[8] (RVA/Human wt/THA/LS-04/2013/G2P[8]) genotypes were identified in fecal samples from hospitalized children with acute gastroenteritis. In this study, we sequenced and characterized the complete genomes of strains SKT-281, SKT-289, and LS-04. On whole genomic analysis, all three strains exhibited unique genotype constellations including both genogroup 1 and 2 genes: G3-P[8]-I2-R2-C2-M2-A2-N2 T2-E2-H2 for strains SKT-281 and SKT-289, and G2-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 for strain LS-04. Except for the G genotype, the unique genotype constellation of the three strains (P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2) is commonly shared with DS-1 like G1P[8] strains. On phylogenetic analysis, nine of the 11 genes of strains SKT-281 and SKT-289 (VP4, VP6, VP1-3, NSP1-3, and NSP5) appeared to have originated from DS-1-like G1P[8] strains, while the remaining VP7 and NSP4 genes appeared to be of equine and bovine origin, respectively. Thus, strains SKT-281 and SKT-289 appeared to be reassortant strains as to DS-1-like G1P[8], animal derived human, and/or animal rotaviruses. On the other hand, seven of the 11 genes of strain LS-04 (VP7, VP6, VP1, VP3, and NSP3-5) appeared to have originated from locally circulating DS-1-like G2P[4] human rotaviruses, while three genes (VP4, VP2, and NSP1) were assumed to be derived from DS-1-like G1P[8] strains. Notably, the remaining NSP2 gene of strain LS-04 appeared to be of bovine origin. Thus, strain LS-04 was assumed to be a multiple reassortment strain as to DS-1-like G1P[8], locally circulating DS-1-like G2P[4], bovine-like human, and/or bovine rotaviruses. Overall, the great genomic diversity among the DS-1-like G1P[8] strains seemed to have been generated through reassortment involving human and animal strains. To our knowledge, this is the first report on whole genome-based characterization of DS-1-like intergenogroup reassortant strains having G3P[8] and G2P[8] genotypes that have emerged in Thailand. Our observations will provide important insights into the evolutionary dynamics of emerging DS-1-like G1P[8] strains and related reassortant ones. PMID- 26845442 TI - The spectrum of respiratory pathogens among returning Hajj pilgrims: myths and reality. AB - Enhanced surveillance systems have been implemented recently in many countries in order to rapidly detect and investigate any possible cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection among travellers returning from the Middle East, including notably Hajj pilgrims. According to the available surveillance data, only a few sporadic travel-associated MERS-CoV cases have been reported outside the Arabian Peninsula so far, mainly in Europe, North Africa, and Asia. These have resulted in no cases, or limited numbers of secondary cases except in Korea. The vast majority of viral respiratory infections in pilgrims returning home have been due to seasonal influenza viruses, rhinoviruses, and other known coronaviruses distinct from the MERS coronavirus. Influenza vaccination should be a priority for all Hajj pilgrims, as recommended by experts. PMID- 26845443 TI - Aspergillus mediastinitis after cardiac surgery. AB - BACKGROUND: Mediastinitis is a serious complication after cardiac surgery. While bacteria are the more common pathogens, fungal infections are rare. In particular, several cases of postoperative Aspergillus mediastinitis have been reported, the majority of which had an extremely poor outcome. METHODS: A case of mediastinitis in a 42-year-old patient due to Aspergillus fumigatus after cardiac surgery is described. Two main risk factors were found: cardiogenic shock requiring veno-arterial extracorporeal life support and failure of primary closure of the sternum. A full recovery was attained after surgical drainage and antifungal therapy with liposomal amphotericin B, followed by a combination of voriconazole and caspofungin. The patient was followed for 18 months without relapse. RESULTS: This is an extremely rare case of postoperative Aspergillus mediastinitis exhibiting a favourable outcome. Based on a systematic review of the literature, previous cases were examined with a focus on risk factors, antifungal therapies, and outcomes. CONCLUSION: The clinical features of postoperative Aspergillus mediastinitis may be paucisymptomatic, emphasizing the need for a low index of suspicion in cases of culture-negative mediastinitis or in indolent wound infections. In addition to surgical debridement, the central component of antifungal therapy should include amphotericin B or voriconazole. PMID- 26845440 TI - Discovery of Novel Hepatitis C Virus NS5B Polymerase Inhibitors by Combining Random Forest, Multiple e-Pharmacophore Modeling and Docking. AB - The NS5B polymerase is one of the most attractive targets for developing new drugs to block Hepatitis C virus (HCV) infection. We describe the discovery of novel potent HCV NS5B polymerase inhibitors by employing a virtual screening (VS) approach, which is based on random forest (RB-VS), e-pharmacophore (PB-VS), and docking (DB-VS) methods. In the RB-VS stage, after feature selection, a model with 16 descriptors was used. In the PB-VS stage, six energy-based pharmacophore (e-pharmacophore) models from different crystal structures of the NS5B polymerase with ligands binding at the palm I, thumb I and thumb II regions were used. In the DB-VS stage, the Glide SP and XP docking protocols with default parameters were employed. In the virtual screening approach, the RB-VS, PB-VS and DB-VS methods were applied in increasing order of complexity to screen the InterBioScreen database. From the final hits, we selected 5 compounds for further anti-HCV activity and cellular cytotoxicity assay. All 5 compounds were found to inhibit NS5B polymerase with IC50 values of 2.01-23.84 MUM and displayed anti-HCV activities with EC50 values ranging from 1.61 to 21.88 MUM, and all compounds displayed no cellular cytotoxicity (CC50 > 100 MUM) except compound N2, which displayed weak cytotoxicity with a CC50 value of 51.3 MUM. The hit compound N2 had the best antiviral activity against HCV, with a selective index of 32.1. The 5 hit compounds with new scaffolds could potentially serve as NS5B polymerase inhibitors through further optimization and development. PMID- 26845444 TI - Nodding syndrome--we can now prevent it. PMID- 26845441 TI - The Malarial Exported PFA0660w Is an Hsp40 Co-Chaperone of PfHsp70-x. AB - Plasmodium falciparum, the human pathogen responsible for the most dangerous malaria infection, survives and develops in mature erythrocytes through the export of proteins needed for remodelling of the host cell. Molecular chaperones of the heat shock protein (Hsp) family are prominent members of the exportome, including a number of Hsp40s and a Hsp70. PFA0660w, a type II Hsp40, has been shown to be exported and possibly form a complex with PfHsp70-x in the infected erythrocyte cytosol. However, the chaperone properties of PFA0660w and its interaction with human and parasite Hsp70s are yet to be investigated. Recombinant PFA0660w was found to exist as a monomer in solution, and was able to significantly stimulate the ATPase activity of PfHsp70-x but not that of a second plasmodial Hsp70 (PfHsp70-1) or a human Hsp70 (HSPA1A), indicating a potential specific functional partnership with PfHsp70-x. Protein binding studies in the presence and absence of ATP suggested that the interaction of PFA0660w with PfHsp70-x most likely represented a co-chaperone/chaperone interaction. Also, PFA0660w alone produced a concentration-dependent suppression of rhodanese aggregation, demonstrating its chaperone properties. Overall, we have provided the first biochemical evidence for the possible role of PFA0660w as a chaperone and as co-chaperone of PfHsp70-x. We propose that these chaperones boost the chaperone power of the infected erythrocyte, enabling successful protein trafficking and folding, and thereby making a fundamental contribution to the pathology of malaria. PMID- 26845446 TI - MicroRNA-133a Inhibits Osteosarcoma Cells Proliferation and Invasion via Targeting IGF-1R. AB - BACKGROUND/AIMS: MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate gene expression by repressing translation or cleaving RNA transcripts in a sequence-specific manner. Downregulated microRNAs and their roles in cancer development have attracted much attention. A growing body of evidence showed that microRNA-133a (miR-133a) has inhibitory effects on cell proliferation, migration, invasion, and metastasis of osteosarcoma. METHODS: MiR-133a expression in human osteosarcoma cell lines and human normal osteoblastic cell line hFOB was investigated by real-time PCR (RT-PCR). The role of miR-133a in human osteosarcoma growth and invasion was assessed in cell lines in vitro and in vivo. Then, luciferase reporter assay validated IGF-1R as a downstream and functional target of miR-133a, and functional studies revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of IGF-1R expression. RESULTS: MiR-133a was lower expressed in human osteosarcoma cell lines than human normal osteoblastic cell line hFOB and its effect on inhibiting proliferation, invasion and metastasis is mediated by its direct interaction with the IGF-1R. Furthermore, the tumour-suppressive function of miR-133a probably contributed to inhibiting the activation AKT and ERK signaling pathway. CONCLUSION: MiR-133a suppresses osteosarcoma progression and metastasis by targeting IGF-1R in human osteosarcoma cells, providing a novel candidate prognostic factor and a potential anti-metastasis therapeutic target in osteosarcoma. PMID- 26845445 TI - Structure-Function Modeling of Optical Coherence Tomography and Standard Automated Perimetry in the Retina of Patients with Autosomal Dominant Retinitis Pigmentosa. AB - PURPOSE: To assess relationships between structural and functional biomarkers, including new topographic measures of visual field sensitivity, in patients with autosomal dominant retinitis pigmentosa. METHODS: Spectral domain optical coherence tomography line scans and hill of vision (HOV) sensitivity surfaces from full-field standard automated perimetry were semi-automatically aligned for 60 eyes of 35 patients. Structural biomarkers were extracted from outer retina b scans along horizontal and vertical midlines. Functional biomarkers were extracted from local sensitivity profiles along the b-scans and from the full visual field. These included topographic measures of functional transition such as the contour of most rapid sensitivity decline around the HOV, herein called HOV slope for convenience. Biomarker relationships were assessed pairwise by coefficients of determination (R2) from mixed-effects analysis with automatic model selection. RESULTS: Structure-function relationships were accurately modeled (conditional R(2)>0.8 in most cases). The best-fit relationship models and correlation patterns for horizontally oriented biomarkers were different than vertically oriented ones. The structural biomarker with the largest number of significant functional correlates was the ellipsoid zone (EZ) width, followed by the total photoreceptor layer thickness. The strongest correlation observed was between EZ width and HOV slope distance (marginal R(2) = 0.85, p<10(-10)). The mean sensitivity defect at the EZ edge was 7.6 dB. Among all functional biomarkers, the HOV slope mean value, HOV slope mean distance, and maximum sensitivity along the b-scan had the largest number of significant structural correlates. CONCLUSIONS: Topographic slope metrics show promise as functional biomarkers relevant to the transition zone. EZ width is strongly associated with the location of most rapid HOV decline. PMID- 26845447 TI - Downregulation of tumor suppressing STF cDNA 3 promotes epithelial-mesenchymal transition and tumor metastasis of osteosarcoma by the Wnt/GSK-3beta/beta catenin/Snail signaling pathway. AB - Epithelial to mesenchymal transition (EMT) has received considerable attention as a conceptual paradigm for explaining the invasive and metastatic behavior of cells during cancer progression. Our previous study showed that loss of expression of TSSC3 is positively associated with osteosarcoma malignancy and progression. However, whether TSSC3 mediates EMT in osteosarcoma is poorly understood. In the present study, we determined that TSSC3 downregulation induced cell migration and invasion ability and promoted mesenchymal transition of osteosarcoma cells by upregulating mesenchymal markers and inhibiting the epithelial markers. Furthermore, TSSC3 downregulation elicited a signaling cascade that included increased levels of Wnt3a and LRP5, inactivation of GSK 3beta, accumulation of nuclear beta-catenin and Snail, the augmented binding of beta-catenin to TCF-4, and accordingly increased the expression of Wnt target genes (CD44, MMP7). The gene knockdown of these signaling proteins could inhibit TSSC3 downregulation-promoted EMT, migration, and invasion in osteosarcoma. Finally, TSSC3 overexpression obviously inhibited cell migration, invasion, and repressed mesenchymal phenotypes, reducing lung metastasis through GSK-3beta activation. Collectively, TSSC3 downregulation promotes the EMT of osteosarcoma cells by regulating EMT markers via a signal transduction pathway that involves Snail, Wnt-beta-catenin/TCF, and GSK-3beta. PMID- 26845448 TI - VNN1, a potential biomarker for pancreatic cancer-associated new-onset diabetes, aggravates paraneoplastic islet dysfunction by increasing oxidative stress. AB - In our previous clinical microarray analysis, we were the first to report on Vanin-1 (VNN1) as a novel clinically derived biomarker of pancreatic cancer associated new-onset diabetes (PCAND). The functional mechanisms of VNN1 in the pathogenesis of PCAND, however, are not completely understood. In the present study, we further extend our previous clinical study to include laboratory research. The functions and mechanisms of neoplastic overexpressed VNN1 in PCAND have been explored using a co-culture model. Furthermore, the serum concentrations and discrimination power of downstream molecules of VNN1 were tested in a PCAND cohort. Pancreatic ductal adenocarcinoma (PDA) overexpressed VNN1 further aggravates paraneoplastic islet dysfunction; decreases in GSH/PPAR gamma concentrations and increases in ROS/cysteamine might be primary cause of this effect. Clinical serum analyses revealed that the expression profiles of these molecules were aberrant in the PCAND group. Our results further demonstrated that PCAND is a type of paraneoplastic diabetes. As the only clinically derived biomarker for PCAND screening available today, the biological role of VNN1 in triggering oxidative stress within the pancreatic microenvironment is important. The molecules downstream of VNN1 are also potential biomarkers for PCAND screening. PMID- 26845449 TI - Tumor microenvironment and therapeutic response. AB - The tumor microenvironment significantly influences therapeutic response and clinical outcome. Microenvironment-mediated drug resistance can be induced by soluble factors secreted by tumor or stromal cells. The adhesion of tumor cells to stromal fibroblasts or to components of the extracellular matrix can also blunt therapeutic response. Microenvironment-targeted therapy strategies include inhibition of the extracellular ligand-receptor interactions and downstream pathways. Immune cells can both improve and obstruct therapeutic efficacy and may vary in their activation status within the tumor microenvironment; thus, re programme of the immune response would be substantially more beneficial. The development of rational drug combinations that can simultaneously target tumor cells and the microenvironment may represent a solution to overcome therapeutic resistance. PMID- 26845450 TI - Gender differences in emotion experience perception under different facial muscle manipulations. AB - According to embodied emotion theory, facial manipulations should modulate and initiate particular emotions. However, whether there are gender differences in emotion experience perception under different facial muscle manipulations is not clear. Therefore, we conducted two behavioral experiments to examine gender differences in emotional perception in response to facial expressions (sad, neutral, and happy) under three conditions: (1) holding a pen using only the teeth (HPT), which facilitates the muscles typically associated with smiling; (2) holding a pen using only the lips (HPL), which inhibits the muscles typically associated with smiling; and (3) a control condition--hold no pen (HNP). We found that HPT made the emotional feelings more positive, and that the change degree of female's ratings of sad facial expressions between conditions (HPL to HPT) was larger than males'. These results suggested cognition can be affected by the interaction of the stimuli and the body, especially the female. PMID- 26845451 TI - Effects of Protection and Sediment Stress on Coral Reefs in Saint Lucia. AB - The extent to which Marine Protected Areas (MPAs) benefit corals is contentious. On one hand, MPAs could enhance coral growth and survival through increases in herbivory within their borders; on the other, they are unlikely to prevent disturbances, such as terrestrial runoff, that originate outside their boundaries. We examined the effect of spatial protection and terrestrial sediment on the benthic composition of coral reefs in Saint Lucia. In 2011 (10 to 16 years after MPAs were created), we resurveyed 21 reefs that had been surveyed in 2001 and analyzed current benthic assemblages as well as changes in benthic cover over that decade in relation to protection status, terrestrial sediment influence (measured as the proportion of terrigenous material in reef-associated sediment) and depth. The cover of all benthic biotic components has changed significantly over the decade, including a decline in coral and increase in macroalgae. Protection status was not a significant predictor of either current benthic composition or changes in composition, but current cover and change in cover of several components were related to terrigenous content of sediment deposited recently. Sites with a higher proportion of terrigenous sediment had lower current coral cover, higher macroalgal cover and greater coral declines. Our results suggest that terrestrial sediment is an important factor in the recent degradation of coral reefs in Saint Lucia and that the current MPA network should be complemented by measures to reduce runoff from land. PMID- 26845452 TI - Comprehensive, Population-Based Sensitivity Analysis of a Two-Mass Vocal Fold Model. AB - Previous vocal fold modeling studies have generally focused on generating detailed data regarding a narrow subset of possible model configurations. These studies can be interpreted to be the investigation of a single subject under one or more vocal conditions. In this study, a broad population-based sensitivity analysis is employed to examine the behavior of a virtual population of subjects and to identify trends between virtual individuals as opposed to investigating a single subject or model instance. Four different sensitivity analysis techniques were used in accomplishing this task. Influential relationships between model input parameters and model outputs were identified, and an exploration of the model's parameter space was conducted. Results indicate that the behavior of the selected two-mass model is largely dominated by complex interactions, and that few input-output pairs have a consistent effect on the model. Results from the analysis can be used to increase the efficiency of optimization routines of reduced-order models used to investigate voice abnormalities. Results also demonstrate the types of challenges and difficulties to be expected when applying sensitivity analyses to more complex vocal fold models. Such challenges are discussed and recommendations are made for future studies. PMID- 26845453 TI - Diaphragmatic fatigue during inspiratory muscle loading in normoxia and hypoxia. AB - INTRODUCTION: Diaphragmatic fatigue (DF) occurs during strenuous loading of respiratory muscles (e.g., heavy-intensity whole-body exercise, normocapnic hyperpnea, inspiratory resistive breathing). DF develops early on during normoxia, without further decline toward task failure; however, its progression during inspiratory muscle loading in during hypoxia remains unclear. Therefore, the present study used volume-corrected transdiaphragmatic pressures during supramaximal magnetic phrenic nerve stimulation (Pdi,twc) to investigate the effect of hypoxia on the progression of diaphragmatic fatigue during inspiratory muscle loading. METHODS: Seventeen subjects completed two standardized rounds of inspiratory muscle loading (blinded, randomized) under the following conditions: (i) normoxia, and (ii) normobaric hypoxia (SpO2 80%), with Pdi,twc assessment every 45 s. RESULTS: In fatiguers (i.e., Pdi,twc reduction >10%, n=10), biometric approximation during normoxia is best represented by Pdi,twc=4.06+0.83 exp(-0.19 * x), in contrast to Pdi,twc=4.38-(0.05 * x) during hypoxia. CONCLUSION: Progression of diaphragmatic fatigue during inspiratory muscle loading assessed by Pdi,tw differs between normoxia and normobaric hypoxia: in the former, Pdi,tw follows an exponential decay, whereas during hypoxia, Pdi,tw follows a linear decline. PMID- 26845454 TI - Interactive effects of hypoxia, carbon monoxide and acute lung injury on oxygen transport and aerobic capacity. AB - This study determined how breathing hypoxic gas, reducing circulatory capacitance for O2 by breathing CO, and impairing pulmonary gas exchange by acutely injuring the lungs interact to limit cardiopulmonary O2 delivery, O2 extraction and maximal aerobic capacity (VO2max). Five goats ran on a treadmill at VO2max following oleic-acid induced acute lung injury that impaired pulmonary gas exchange, after partial recovery or with no acute lung injury. Goats breathed normoxic or hypoxic inspired gas fractions (FIO2 0.21 or 0.12) with and without small amounts of CO to maintain carboxyhemoglobin fractions (FHbCO) of 0.02 or 0.30. With the exception of elevated FHbCO with acute lung injury (P=0.08), all combinations of hypoxia, elevated FHbCO and acute lung injury attenuated the reduction in VO2max by 15-27% compared to the sum of each treatment's individual reduction in VO2max when administered separately. Simultaneous administration of two treatments attenuated the reduction in VO2max by attenuating the decrease in cardiopulmonary O2 delivery, not synergistically increasing O2 extraction. PMID- 26845455 TI - Multi-walled carbon nanotubes with selected properties for dynamic filtration of pharmaceuticals and personal care products. AB - In this study, multi-walled carbon nanotubes (MWCNT) with selected properties, including pristine MWCNT, hydroxylated MWCNT (H-MWCNT), thin-walled MWCNT with large inner diameter (L-MWCNT), aminated MWCNT, and high-purity MWCNT were investigated for dynamic removal of eight pharmaceuticals and personal care products (PPCP). The removal ratios of different PPCP by the pristine MWCNT followed a decreasing order of triclosan (0.93) > prometryn (0.71) > 4 acetylamino-antipyrine (0.67) > carbendazim (0.65) > caffeine (0.42) > ibuprofen (0.34) > acetaminophen (0.29) at 100 min of filtration. Similar or even higher PPCP removals were obtained for all PPCP as the influent concentration decreased, suggesting potential consistent PPCP removals at environmental PPCP concentrations. The removal ratio of acetaminophen was increased to 0.74 by using H-MWCNT. SRFA (Suwannee River fulvic acid) suppressed PPCP adsorption to MWCNT, to greater extents with increasing SRFA concentrations. The L-MWCNT, despite a large inner diameter of 52 +/- 3 nm, did not provide better resistance to the competitive adsorption of SRFA than MWCNT with a small inner diameter of 10 +/- 2 nm. Future research will be conducted to minimize the effect of SRFA and facilitate application of MWCNT to the treatment of PPCP-contaminated water. PMID- 26845456 TI - Hydrophobicity of biofilm coatings influences the transport dynamics of polystyrene nanoparticles in biofilm-coated sand. AB - Engineered nanoparticles (ENPs) are used in the manufacture of over 2000 industrial and consumer products to enhance their material properties and functions or to enable new nanoparticle-dependent functions. The widespread use of ENPs will result in their release to the subsurface and aquatic environments, where they will interact with indigenous biota. Laboratory column experiments were designed to understand the influence of two different Pseudomonas aeruginosa biofilms on the mobility of polystyrene latex nanoparticles in granular porous media representative of groundwater aquifers or riverbank filtration settings. The transport behavior of 20 nm carboxylate-modified (CLPs) and sulfate (SLPs) polystyrene latex ENPs suspended in NaCl or CaCl2 (1 and 10 mM ionic strength, pH 7) was studied in columns packed with quartz sand coated with biofilms formed by two P. aeruginosa strains that differed in cell surface hydrophobicity (P. aeruginosa 9027TM, relatively hydrophilic and P. aeruginosa PAO1, relatively hydrophobic). Biofilm-coated quartz sand retained more of the electrostatically stabilized latex ENPs than clean, uncoated sand, regardless of the serotype. As IS increased, clear differences in the shape of the ENP breakthrough curves were observed for each type of biofilm coating. ENP breakthrough in the P. aeruginosa PAO1 biofilm-coated sand was generally constant with time whereby breakthrough in the P. aeruginosa 9027 biofilm-coated sand showed dynamic behavior. This indicates a fundamental difference in the mechanisms of ENP deposition onto hydrophilic or hydrophobic biofilm coatings due to the hydration properties of these biofilms. The results of this study demonstrate the importance of considering the surface properties of aquifer grain coatings when evaluating ENP fate in natural subsurface environments. PMID- 26845457 TI - Racial, ethnic, and socioeconomic disparities in pituitary surgery outcomes. AB - OBJECTIVES/HYPOTHESIS: To investigate the association of race, ethnicity, socioeconomic status, and hospital volume with outcomes in pituitary surgery. STUDY DESIGN: Retrospective cross-sectional study of the 2008-2012 National (Nationwide) Inpatient Sample. METHODS: Patient demographics, hospital characteristics, postoperative complications, and in-hospital mortality for patients undergoing pituitary surgery were compared between white, black, and Hispanic patients. Hierarchal logistic regression analysis was used to assess the association of patient and hospital variables on complication rates. RESULTS: A total of 8,812 patients met the inclusion criteria, and 5,924 (67.2%) patients were white, 1,590 (18.0%) were black, and 1,296 (14.7%) were Hispanic. Black and Hispanic patients were more likely to live in the poorest income areas, be insured with Medicaid, and be treated at lower-volume pituitary surgery centers. Patients with Medicaid had a higher likelihood of complications compared to Medicare patients, whereas patients with private insurance were significantly less likely to experience any complications. Likelihood of complications was significantly higher for patients treated at lower-volume pituitary surgery centers. When controlled for patient and hospital characteristics, regression analysis showed that the likelihood of postoperative complications was higher in black and Hispanic patients compared to white patients. CONCLUSIONS: Racial, ethnic, and socioeconomic disparities exist for outcomes after pituitary surgery. Black and Hispanic patients have worse postoperative outcomes compared to white patients, as well as disproportionate utilization of Medicaid and low-volume pituitary surgery centers. Further investigations are necessary to uncover the sources of these disparities in an effort to provide safer and more affordable care to all patients. LEVEL OF EVIDENCE: 2c. PMID- 26845458 TI - High Testosterone Preoperative Plasma Levels Independently Predict Biopsy Gleason Score Upgrading in Men with Prostate Cancer Undergoing Radical Prostatectomy. AB - PURPOSE: The study aims to investigate the potential associations between preoperative plasma levels of total testosterone (TT) and biopsy Gleason score (bGS) upgrading in prostate cancer (PCA) patients undergoing radical prostatectomy (RP). MATERIALS AND METHODS: Exclusion criteria were treatment with 5alpha-reductase inhibitors, LH-releasing hormone analogues or testosterone replacement. Criteria of bGS upgrading were as follows: (i) bGS 6 to pathological Gleason score (pGS) >6, (ii) bGS 7 with pattern 3 + 4 to pGS 7 with pattern 4 + 3 or to pGS >7, (iii) bGS 7 with pattern 4 + 3 to pGS >7. Patients who showed bGS >7 were excluded from the cohort. RESULTS: The study included 209 patients. Tumor upgrading was assessed in 76 (36.4%) cases of the entire cohort, in 51 out of 130 cases (39.2%) of the bGS 6 group and 25 out of 79 patients (31.6%) in the bGS 7 cluster. Logistic regression models showed that independent clinical covariates predicting the risk of bGS upgrading included TT (OR 1.058; p = 0.027) and prostate-specific antigen (PSA) density (OR 23.3; p = 0.008) as well as TT (OR 1.057; p = 0.029) with PSA (OR 1.061; p = 0.023). The model suggests that 1 unit increase in TT plasma levels increases the odds of bGS upgrading by 5.8 or 5.7%. CONCLUSIONS: In summary, we have determined that high TT preoperative plasma levels independently predict bGS upgrading in men with PCA undergoing RP. Preoperative plasma levels of TT might be included as a potential marker for assessing the risk bGS upgrading. PMID- 26845459 TI - Temporal changes in the response of SVZ neural stem cells to intraventricular administration of growth factors. AB - In vivo growth factor (GF) treatment is a promising approach to enhance the regenerative capacity of neural stem cells (NSCs) for brain repair. However, how exogenous GFs affect endogenous NSCs is not well understood. This study investigated the impact of intraventricular administration of fibroblast growth factor 2 and epidermal growth factor on NSCs in the subventricular zone of intact adult mice. GFs were administered for various periods (3, 7, 10, and 14 days), and the proliferation and neuronal production of NSCs were assessed during and after GF treatment. We found that proliferation of NSCs and their progeny is markedly augmented during the first 7 days after the initiation of GF treatment. GF treatment for longer periods, however, did not lead to further increases in the NSC pool, but rather attenuated such proliferation and inhibited neurogenesis. As a result, the production of new olfactory bulb neurons was increased in animals treated with GFs for 7 days but decreased in animals treated for 14 days. These results show time-dependent changes in the response of NSCs to exogenous GFs and demonstrate that precise control of the duration of GF treatment is important for significant enhancement of neuronal production by NSCs in vivo for brain repair. PMID- 26845460 TI - Knowledge of evidence-based guidelines in Ventilator-Associated Pneumonia prevention. AB - OBJECTIVE: The purpose of this study was to assess the intensive care unit nurses' knowledge of evidence-based guidelines for ventilator-associated pneumonia (VAP) prevention at Guilan University of Medical Sciences (GUMS) hospitals, Guilan Province, northern Iran. METHODS: This cross-sectional study included 219 nurses working in 14 intensive care units at 11 Guilan hospitals. The questionnaire consisted of three parts of demographic information, nurses' knowledge of evidence-based guidelines for the prevention of VAP, and the barrier for the implementation of these guidelines. RESULTS: Of the 219 nurses, 171 (response rate 78.1%) participated in this study, and their mean knowledge score was 4.6. There was no significant relation between nurses' knowledge score and their work experience (P = 0.327), education degree (P = 0.189), and their position (P = 0.168). CONCLUSION: The level of knowledge regarding VAP prevention seems inadequate in the present study. Although having knowledge about the principles of evidence-based care cannot guarantee the implementation of these principles, lack of knowledge may be a potential barrier to adherence to evidence based guidelines for the prevention of VAP. This article is protected by copyright. All rights reserved. PMID- 26845461 TI - Structural variation detection using next-generation sequencing data: A comparative technical review. AB - Structural variations (SVs) are mutations in the genome of size at least fifty nucleotides. They contribute to the phenotypic differences among healthy individuals, cause severe diseases and even cancers by breaking or linking genes. Thus, it is crucial to systematically profile SVs in the genome. In the past decade, many next-generation sequencing (NGS)-based SV detection methods have been proposed due to the significant cost reduction of NGS experiments and their ability to unbiasedly detect SVs to the base-pair resolution. These SV detection methods vary in both sensitivity and specificity, since they use different SV property-dependent and library-property-dependent features. As a result, predictions from different SV callers are often inconsistent. Besides, the noises in the data (both platform-specific sequencing error and artificial chimeric reads) impede the specificity of SV detection. Poorly characterized regions in the human genome (e.g., repeat regions) greatly impact the reads mapping and in turn affect the SV calling accuracy. Calling of complex SVs requires specialized SV callers. Apart from accuracy, processing speed of SV caller is another factor deciding its usability. Knowing the pros and cons of different SV calling techniques and the objectives of the biological study are essential for biologists and bioinformaticians to make informed decisions. This paper describes different components in the SV calling pipeline and reviews the techniques used by existing SV callers. Through simulation study, we also demonstrate that library properties, especially insert size, greatly impact the sensitivity of different SV callers. We hope the community can benefit from this work both in designing new SV calling methods and in selecting the appropriate SV caller for specific biological studies. PMID- 26845462 TI - MALDI MSI analysis of lipid changes in living skin equivalents in response to emollient creams containing palmitoylethanolamide. AB - Mass spectrometry imaging (MSI) is a powerful tool for the study of intact tissue sections. The use of matrix-assisted laser desorption/ionisation (MALDI) MSI for the study of the distribution and effect of emollient treatment on sections of reconstructed living skin equivalents during their development and maturation is described. Living skin equivalent (LSE) samples were obtained at 14days development, re-suspended in maintenance medium and incubated for 24h after delivery. The medium was changed, the LSE treated with either Physiogel A.I.(r) or Oilatum Junior(r) emollients and then re-incubated and samples taken at 4, 6 and 24h time points. Mass spectra and mass spectral images were recorded from 12MUm sections of the LSE taken at each time point for comparison using MALDI mass spectrometry (MS). It was possible to detect ions characteristic of each emollient in the LSE. In addition a number of lipid species previously reported as being significant in the maturation of the LSE were observable. At the 24h time point, the images revealed what appeared to be differences in the organisation of the skin cells observed across the Physiogel A.I.(r) treatment group tissue sections when directly compared to the untreated tissue group. PMID- 26845463 TI - Introducing smoking cessation to Indonesian males treated for tuberculosis: The challenges of low-moderate level smoking. AB - There is a dearth of information about the smoking habits of people currently and formerly treated for tuberculosis (TB) in low- and middle-income countries (LMICs). In this paper we describe research carried out in Indonesia between 2007 and 2011 designed to investigate both the impact of TB-specific quit smoking messages in the TB clinic and at home, and shifts in patterns of smoking among those formerly treated for TB who continue to smoke. The results of a modest two arm smoking cessation trial involving 87 patients undergoing Directly Observed Therapy Short course treatment (DOTS) for TB are presented. In one arm patients received a TB-specific quit smoking message delivered by doctors and a TB and smoking educational booklet and quit smoking guide. In the second, family support arm, patients also received on-going cessation messages delivered by family members trained to be DOTS supporters. The study followed patients twice during their six months of DOTS treatment and twice six months post treatment. Both arms of the study reduced rates of smoking during and following TB treatment significantly with 73% of patients in the doctor arm and 71% in the family support arm remaining quit at the end of the treatment (month 6). When complete abstinence at six months after treatment was taken as a primary outcome measure, no statistical difference was found in the effectiveness of the two arms of the intervention. Notably, 67% of higher-level smokers at baseline and 33% of low moderate level smokers at baseline quit entirely. Many of those who resumed smoking did so at low-moderate levels (<6 cigarettes a day). Eighty-four percent of patients who quit during treatment maintained their abstinence six months after treatment, 13% resumed smoking at a low-moderate level (<6 cigarettes), and only 3% resumed smoking at a higher level. A purposeful sample of 15 patients who shifted from heavy smoking (20-40 cigarettes per day) to low-moderate levels of smoking post treatment were followed for an additional 12 months. We report on their ability to sustain lower levels of smoking and self-perceived smoking status given their dramatic reduction in cigarette consumption. This is the first study of low-moderate level smoking among patients formerly treated for TB conducted anywhere in South-East Asia. PMID- 26845464 TI - Nitrogen removal properties in a continuous marine anammox bacteria reactor under rapid and extensive salinity changes. AB - Salinity tolerance is one of the most important factors for the application of bioreactors to high-salinity wastewater. Although marine anammox bacteria (MAB) might be expected to tolerate higher salinities than freshwater anammox bacteria, there is little information on the effects of salinity on MAB activity. This study aimed to reveal the nitrogen removal properties in a continuous MAB reactor under conditions of rapid and extensive salinity changes. The reactor demonstrated stable nitrogen removal performance with a removal efficiency of over 85% under salinity conditions ranging from 0 to 50 g/L NaCl. The reactor performance was also well maintained, even though the salinity was rapidly changed from 30 to 50 g/L and from 30 to 0 g/L. Other evidence suggested that the seawater medium used contained components essential for effective MAB performance. Bacterial community analysis using polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE) showed that planctomycete UKU 1, the dominant MAB species in the inoculum, was the main contributor to anammox activity under all conditions. The PCR-DGGE using a universal bacterial primer set showed different DNA band patterns between the reactor biomass sample collected under conditions of 75 g/L NaCl and all other conditions (0, 30, 50 and freshwater-medium). All DNA sequences determined were very similar to those of bacterial species from marine environments, anaerobic environments, or wastewater treatment facilities. PMID- 26845465 TI - Biodegradation of sulfamethoxazole photo-transformation products in a water/sediment test. AB - Occurrence of the antibiotic sulfamethoxazole (SMX) in the aquatic environment is of concern due to its potential to induce antibiotic resistance in pathogenic bacteria. While degradation of SMX can occur by numerous processes, the environmental fate of its transformation products (TPs) remains poorly understood. In the present work, biodegradation of SMX photo-TPs was investigated in a water/sediment system. Photo-TPs were produced by exposing SMX to artificial sunlight for 48 h. The resulting mixture of 8 photo-TPs was characterized using a combination of ultra-high performance liquid chromatography coupled to high resolution mass spectrometry and tandem mass spectrometry, and then used in biodegradation experiments. Significant differences in transformation among SMX photo-TPs were observed in the water/sediment system, with four photo-TPs displaying evidence of biodegradation (dissipation half-lives [DT50] of 39.7 d for 3-amino-5-methylisoxazole, 12.7 d for 4-nitro-sulfamethxoazole, 7.6 d for an SMX isomer and 2.4 d for [C10H13N3O4S]), two displaying primarily abiotic degradation (DT50 of 31 d for sulfanilic acid and 74.9 d for 5-methylisoxazol-3 yl-sulfamate), and two photo-TPs behaving largely recalcitrantly. Remarkably, TPs previously reported to be photo-stable also were persistent in biodegradation experiments. The most surprising observation was an increase in SMX concentrations when the irradiated solution was incubated, which we attribute to back-transformation of certain photo-TPs by sediment bacteria (85% from 4-nitro sulfamethoxazole). This process could contribute to exposure to SMX in the aquatic environment that is higher than one would expect based on the fate of SMX alone. The results highlight the importance of considering TPs along with their parent compounds when characterizing environmental risks of emerging contaminants. PMID- 26845466 TI - To improve the quality of life in elderly people. PMID- 26845467 TI - Robotic left hepatectomy and Roux-en-Y right hepatico-jejunostomy for biliary papillomatosis. PMID- 26845468 TI - Trampoline-related injuries in Hong Kong. PMID- 26845469 TI - Please please me. PMID- 26845470 TI - Ability to detect hypoglycaemic symptoms. PMID- 26845471 TI - De novo transcriptome sequencing and analysis of Rapana venosa from six different developmental stages using Hi-seq 2500. AB - The carnivorous whelk Rapana venosa is regarded as a biological invader with strong ecological fitness in the United States, Argentina, France and other countries. R. venosa may seriously damage bivalve resources. Nonetheless, in China, R. venosa is an important commercial species. Larval development, especially metamorphosis, influences the natural population and industrial breeding. However, there are few studies on the early development of R. venosa, and our understanding is further limited by a lack of genomic information. In this study, de novo sequencing was performed to obtain a comprehensive transcriptome profile during early development. A Hi-seq 2500 sequencing run produced 148,737,902 raw reads that were assembled into 1,137,556 unigenes (average length of 619 nucleotides, of which 49,673 could be annotated). The unigenes were assigned to biological processes and functions after annotation in Gene Ontology, eukaryotic Ortholog Groups and Kyoto Encyclopedia of Genes and Genomes. We also identified 93,196 simple sequence repeats among the unigenes. Six unique sequences associated with neuroendocrine function were analyzed by quantitative real-time PCR. Our data represent the first comprehensive transcriptomic resource for R. venosa. Functional annotation of the unigenes involved in various biological processes could stimulate research on the mechanisms of early development in this species. Understanding the mechanism of early development and metamorphosis would benefit antifouling research and aquaculture of R. venosa. PMID- 26845472 TI - Investigation of flow characteristics in regions of nasal polypoid change. AB - We used computational fluid dynamics to study the airflow characteristics in the ostiomeatal complex/middle turbinate of the human upper airway, where clinically relevant nasal polypoid changes occur (designated Regions A1-A4). We assessed six different flow rates representing one full period of respiration, based on realistic human respiration data, in an anatomically correct numerical model of a patient with a history of polypectomy. The simulation results showed that Regions A1-A4 were not correlated with the local stagnation points where a locally high level of wall pressure was achieved. They, however, exhibited a very distinctive feature in that the positive wall-normal pressure gradients evaluated at the epithelial surface were persistent at six different flow rates spanning the whole respiration period in these areas. Therefore, the regions where polypoid changes developed were thought to be subject to mechanical irritation of the epithelium constantly via locally accelerating airflow moving towards the surface from the airway. On the contrary, relatively large or small values for local wall shear stress were not correlated with Regions A1-A4. PMID- 26845474 TI - Can major laparoscopic liver and pancreas surgery become standard practices? PMID- 26845475 TI - Extraction of Angelica sinensis polysaccharides using ultrasound-assisted way and its bioactivity. AB - In the present article, ultrasound-assisted extraction (UAE) of polysaccharides from Angelica sinensis were investigated. The aim of the study is to examine the extraction parameters such as ultrasound power (140-180W), the ratio of liquid to solid (5-7), extraction time (40-50min) and extraction temperature (80-100 degrees C) and to obtain the best possible combinations of these parameters through response surface methodology (RSM). Based on contour plots and variance analysis, optimum operational conditions for maximizing polysaccharides yield were found to be 180w, 7, 45min and 90 degrees C. Under the optimum operating conditions determined, 6.96% polysaccharides were achieved. In addition, the results showed that A. sinensis polysaccharides (ASP) could increase antioxidant enzymes activities and decrease the MDA levels in the skeletal muscle of exhaustive exercise rats. This study provides strong evidence that A. sinensis polysaccharides supplementation possessed protective effects against exhaustive exercise-induced oxidative stress. PMID- 26845476 TI - Investigation of three lignin complexes with antioxidant and immunological capacities from Inonotus obliquus. AB - Mushroom Inonotus obliquus (I. obliquus), a folk medicine, has been widely used to treat several human malicious tumors since 16th century. In this study, three homogenous biomolecules (designated IOA1, IOA2 and IOA3) were prepared from the alkali extract of I. obliquus. Their molecular weights were measured to be 6.1 * 10(4), 2.9 * 10(4) and 3.5 * 10(4) g/mol respectively and all of them were characterized as lignin-carbohydrate complexes mainly comprised lignin as well as -25% carbohydrates. Antioxidant assays indicated that all of them exhibited pronounced reductive power and strong scavenging activities on DPPH and hydroxyl radicals in vitro. Immunological tests showed that they could also significantly stimulate nitric oxide production and phagocytic activity in RAW 264.7 macrophages. These results implied that the lignin-carbohydrate complexes extracted from I. obliquus might be used as novel natural antioxidants or immunostimulants in functional foods or pharmaceutical candidates. PMID- 26845477 TI - Optimization and development of Nisoldipine nano-bioenhancers by novel orthogonal array (L27 array). AB - Our key objective was an attempt to apply a novel statistical method intended for designing, optimizing and developing Nisoldipine nano-bioenhancers using Taguchi (3 * 3=L27) design. This quality improvement orthogonal design array (L27) was used as a mathematical tool to find and study the response prediction of independent as well as significant variables (A=poly-concentration; B=bio enhancer and C=ratio of organic medium). The array orthogonal (3 * 3=L27) at each level/spaces has been studied with respect to responses changeable (dependent factors); entrapment enhancement (X; evaluated using particle size; Y). All through experimentally performed runs, the results showed independent variables effect individually or simultaneously on changeable (dependent) variables. It also predicted significant variable via its "better to best" optimized spaces (independent level) and would be considered as novel statistically advanced oral drug delivery vehicle for anti-hypertensive agents. PMID- 26845478 TI - Supramolecular inclusion complexation of simvastatin with methylated beta cyclodextrins for promoting osteogenic differentiation. AB - Statins are recognized as a potential candidate to induce the regeneration of bone. However, statins are a strongly hydrophobic drug and it is difficult to administer at the local sites. In this study, the inclusion complexes of simvastatin (SV) with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and randomly methylated beta-cyclodextrin (RM-beta-CD) were prepared to improve the water solubility and the osteogenic differentiation ability of the inclusion complexes in MC3T3-E1 cells was investigated. The water-solubility of SV increased linearly upon the addition of both HP-beta-CD and RM-beta-CD, due to the formation of inclusion complexes. The osteogenic differentiation ability of the inclusion complexes were evaluated by the production of alkaline phosphatase (ALP) and late stage osteogenetic gene expression in MC3T3-E1 cells after 14 days of culture. As a result, the RM-beta-CD/SV inclusion complexes showed significantly higher ALP production and the expression of bone sialoprotein (BSP) and osteocalcin (OCN) than the untreated and free SV-treated cells. Additionally, the production of bone morphogenetic protein-2 (BMP-2) from MC3T3-E1 cells after the treatment with RM-beta-CD/SV inclusion complexes was significantly higher than the untreated and free SV-treated cells. Accordingly, it is concluded that the inclusion complexation of SV with RM-beta-CD is a potential formulation for bone regenerative therapy to improve water-solubility and osteodifferentiation efficiency. PMID- 26845479 TI - Preparation and physical properties of tara gum film reinforced with cellulose nanocrystals. AB - Cellulose nanocrystals (CNC) prepared from microcrystalline cellulose were blended in tara gum solution to prepare nanocomposite films. The morphology, crystallinity, and thermal properties of the CNC and films were evaluated by using transmission electron microscopy, X-ray diffractometry, and thermogravimetric analysis, respectively. The resultant CNC was rod-shaped with diameters of around 8.6 nm. The effect of CNC content on physical and thermal properties of films was studied. The composite film tensile strength increased from 27.86 to 65.73 MPa, elastic modulus increased from 160.98 MPa to 882.49 MPa and the contact angle increased from 55.8 degrees to 98.7 degrees with increasing CNC content from 0 to 6 wt%. However, CNC addition increased the thermal stability slightly and CNC content above 6 wt% decreased the tensile strength by CNC aggregation in the matrix. The nanocomposite film containing 6 wt% CNC possessed the highest light transmittance, mechanical properties, and lowest oxygen permeability. CNC addition is a suitable method to modify tara gum matrix polymer properties. PMID- 26845480 TI - Sodium alginate: An efficient biopolymeric catalyst for green synthesis of 2 amino-4H-pyran derivatives. AB - Sodium alginate, a naturally occurring macromolecule, in its granular form and without any post-modification was found to be an efficient and recoverable bifunctional heterogeneous organocatalyst for the domino synthesis of various 2 amino-3-cyano-4H-pyran annulated derivatives through three-component condensation of different aldehydes, malononitrile and diverse 1,3-dicarbonyl compounds under mild conditions. Corresponding 4H-pyran derivatives were obtained in high to excellent yields after 25-150min stirring in 2mL EtOH under reflux conditions in the presence of 10mol% of sodium alginate, equimolar amounts of aldehydes, malononitrile and 1,3-dicarbonyl compounds. The catalyst was easily separated from the reaction mixture to obtain desired products in excellent purity as shown by FTIR and (1)H NMR spectroscopic methods. Avoiding the use of any transition metal, one-pot and multi-component procedure catalyzed by a renewable biopolymer, the reusability of the catalyst, broad substrate scope and operational simplicity are important features of this methodology for preparation of medicinally important compounds. PMID- 26845481 TI - Chitosan based biocomposite scaffolds for bone tissue engineering. AB - The clinical demand for scaffolds and the diversity of available polymers provide freedom in the fabrication of scaffolds to achieve successful progress in bone tissue engineering (BTE). Chitosan (CS) has drawn much of the attention in recent years for its use as graft material either as alone or in a combination with other materials in BTE. The scaffolds should possess a number of properties like porosity, biocompatibility, water retention, protein adsorption, mechanical strength, biomineralization and biodegradability suited for BTE applications. In this review, CS and its properties, and the role of CS along with other polymeric and ceramic materials as scaffolds for bone tissue repair applications are highlighted. PMID- 26845473 TI - Endoscopist characteristics that influence the quality of colonoscopy. AB - BACKGROUND AND STUDY AIM: Several factors have been shown to be related to colonoscopy quality; however, little is known about the effects of endoscopist factors. This study analyzed the influence of endoscopist-related characteristics on quality indicators for colonoscopy. PATIENTS AND METHODS: The study included 48 endoscopists who each performed at least 20 colonoscopies in the colonoscopy arm of a randomized controlled trial comparing fecal immunochemical test vs. colonoscopy in colorectal cancer screening. These endoscopists performed a total of 3838 procedures in the trial. The following were calculated for each endoscopist: adenoma detection rate (ADR), advanced ADR, proximal ADR, distal ADR, and adenoma per colonoscopy rate (APCR). The characteristics of endoscopists were assessed with regard to colonoscopy quality using multivariate regression analysis. Endoscopist characteristics included age, sex, exclusive endoscopy practice, years as a physician, years as a specialist, specialty, total (life long) number of colonoscopies performed, annual colonoscopy volume, number of hours/week dedicated to endoscopy and number of educational activities in the previous year. RESULTS: Factors associated with ADR were age of the endoscopist (odds ratio [OR] 1.11, 95 % confidence interval [CI] 1.01 - 1.21; P = 0.01) and life-long number of colonoscopies (OR 1.06, 95 %CI 1.01 - 1.11; P = 0.01). Only exclusive dedication to endoscopy practice was found to be independently related to proximal ADR (OR 1.71, 95 %CI 1.15 - 2.74; P = 0.001). Life-long number of colonoscopies was independently related to detection of distal adenomas (OR 1.07, 95 %CI 1.01 - 1.13; P = 0.01). None of the analyzed endoscopist characteristics was associated with advanced ADR or APCR. CONCLUSIONS: This study found that the experience of the endoscopist and exclusive dedication to endoscopy practice, but not annual colonoscopy volume, were associated with better colonoscopy quality. PMID- 26845482 TI - Hydrophilicity improvement of mercerized bacterial cellulose films by polyethylene glycol graft. AB - In this work, polyethylene glycol (PEG), of tree distinct molar masses (200, 300 and 400 g mol(-1)), was grafted onto mercerized bacterial nanocellulose (BNCm) and applied to produce nanofilms (BNCm-PEG). The products BNCm-PEG were characterized by NMR and thermal analysis. Solid-state NMR and X-ray diffraction analyses exhibited no significant differences in index of BNCm-PEG derivatives compared to BNCm, indicating that grafting reaction did not modify the BNCm crystalline structure. The apparent contact angle of the films showed that BNCm PEG films exhibited a pronounced increase in the polar components (BNCm: 8.1 mN m(-1) vs BNCm-PEG400: 29.4 mN m(-1)), and a decrease in dispersive components (BNCm: 41.7 mN m(-1) vs BNCm-PEG400: 35.2 mN m(-1)) of the surface free energy. The BNCm-PEG films were more hydrophilic than BNCm and retained the biocompatibility with L929 fibroblast cells culture. PMID- 26845483 TI - Characterization and safety evaluation of a Deinococcus member as feed additive for hens. AB - As previous studies mainly focus on understanding the mechanisms of radioresistance in Deinococcus bacteria, the present study aimed at characterizing and verifying the safety use of the GKB-Aid 1995 strain, a member of the radiation-resistant bacterial genus Deinococcus, as an ingredient in feed supplements. Using Vitek 2 system and 16S rRNA gene sequencing, GKB-Aid 1995 most resembles Deinococcus grandis. The Ames test, in vitro chromosomal test, in vivo micronucleus test and acute toxicity test were performed subsequently for its safety evaluation. As there is a possibility that the pigment of GKB-Aid 1995 can pass from feed to eggs intended for human consumption, an acute toxicity test was also carried out in pigmented egg yolk. The results confirmed that GKB-Aid 1995 was non-genotoxic in three genotoxicity experiments, and the LD50 of GKB-Aid 1995 and the pigmented egg yolk in ICR mice was greater than 10 and 12 g kg(-1) body weight, respectively. Overall, these data indicate that GKB-Aid 1995 is a non toxic substance with no genotoxicity and is therefore safe to be used as a feed supplement or feed additive. This study suggests there is potential in developing GKB-Aid 1995 as an animal feed additive intended to enhance yolk coloration to meet the demand of consumers. PMID- 26845484 TI - Early signs of range disjunction of submountainous plant species: an unexplored consequence of future and contemporary climate changes. AB - Poleward and upward species range shifts are the most commonly anticipated and studied consequences of climate warming. However, these global responses to climate change obscure more complex distribution change patterns. We hypothesize that the spatial arrangement of mountain ranges and, consequently, climatic gradients in Europe, will result in range disjunctions. This hypothesis was investigated for submountainous forest plant species at two temporal and spatial scales: (i) under future climate change (between 1950-2000 and 2061-2080 periods) at the European scale and (ii) under contemporary climate change (between 1914 1987 and 1997-2013 periods) at the French scale. We selected 97 submountainous forest plant species occurring in France, among which distribution data across Europe are available for 25 species. By projecting future distribution changes for the 25 submountainous plant species across Europe, we demonstrated that range disjunction is a likely consequence of future climate change. To assess whether it is already taking place, we used a large forest vegetation-plot database covering the entire French territory over 100 years (1914-2013) and found an average decrease in frequency (-0.01 +/- 0.004) in lowland areas for the 97 submountainous species - corresponding to a loss of 6% of their historical frequency - along with southward and upward range shifts, suggesting early signs of range disjunctions. Climate-induced range disjunctions should be considered more carefully since they could have dramatic consequences on population genetics and the ability of species to face future climate changes. PMID- 26845485 TI - Mycotic Aneurysm Due to Leclercia Adecarboxylata: A Complication of Vertebral Osteomyelitis. AB - Leclercia adecarboxylata is a gram-negative bacterium and member of Enterobacteriaceae family. It has most frequently been isolated from lower wounds as a part of mixed flora. Mycotic aneurysms were first described by Osler and were mostly associated with infective endocarditis. We present the case of a male who presented with limb vein thrombosis, fatigue, and a history of back pain. The computed tomography scan revealed a saccular aneurysm and combined vertebral osteomyelitis of the third lumbar vertebra. An endovascular aneurysm repair with a tubed endograft was performed. Two years after the initial therapeutic management, he developed buttock claudication because of ostial stenosis of both common iliac arteries and a "kissing-stent" technique was performed. This is the first case described regarding Leclercia adecarboxylata as an etiologic factor of infected aneurysm development, its management and the short-term outcome. PMID- 26845486 TI - Time-Sliced Thawed Gaussian Propagation Method for Simulations of Quantum Dynamics. AB - A rigorous method for simulations of quantum dynamics is introduced on the basis of concatenation of semiclassical thawed Gaussian propagation steps. The time evolving state is represented as a linear superposition of closely overlapping Gaussians that evolve in time according to their characteristic equations of motion, integrated by fourth-order Runge-Kutta or velocity Verlet. The expansion coefficients of the initial superposition are updated after each semiclassical propagation period by implementing the Husimi Transform analytically in the basis of closely overlapping Gaussians. An advantage of the resulting time-sliced thawed Gaussian (TSTG) method is that it allows for full-quantum dynamics propagation without any kind of multidimensional integral calculation, or inversion of overlap matrices. The accuracy of the TSTG method is demonstrated as applied to simulations of quantum tunneling, showing quantitative agreement with benchmark calculations based on the split-operator Fourier transform method. PMID- 26845488 TI - Catalytic SN2'- and Enantioselective Allylic Substitution with a Diborylmethane Reagent and Application in Synthesis. AB - A catalytic method for the site- and enantioselective addition of commercially available di-B(pin)-methane to allylic phosphates is introduced (pin=pinacolato). Transformations may be facilitated by an NHC-Cu complex (NHC=N-heterocyclic carbene) and products obtained in 63-95 % yield, 88:12 to >98:2 S(N)2'/S(N)2 selectivity, and 85:15-99:1 enantiomeric ratio. The utility of the approach, entailing the involvement of different catalytic cross-coupling processes, is highlighted by its application to the formal synthesis of the cytotoxic natural product rhopaloic acid A. PMID- 26845489 TI - A Nitroxide-Tagged Platinum(II) Complex Enables the Identification of DNA G Quadruplex Binding Mode. AB - We reported a novel strategy for investigating small molecule binding to G quadruplexes (GQs). A newly synthesized dinuclear platinum(II) complex (Pt2L) containing a nitroxide radical was shown to selectively bind a GQ-forming sequence derived from human telomere (hTel). Using the nitroxide moiety as a spin label, electron paramagnetic resonance (EPR) spectroscopy was carried out to investigate binding between Pt2L and hTel GQ. Measurements indicated that two molecules of Pt2L bind with one molecule of hTel GQ. The inter-spin distance measured between the two bound Pt2L, together with molecular docking analyses, revealed that Pt2L predominately binds to the neighboring narrow and wide grooves of the G-tetrads as hTel adopts the antiparallel conformation. The design and synthesis of nitroxide tagged GQ binders, and the use of spin-labeling/EPR to investigate their interactions with GQs, will aid the development of small molecules for manipulating GQs involved in crucial biological processes. PMID- 26845490 TI - Self-expanding metal stents for acute refractory esophageal variceal bleeding: A systematic review and meta-analysis. AB - BACKGROUND AND AIM: Esophageal variceal bleeding is a severe complication of portal hypertension with significant morbidity and mortality. A substantial portion of cirrhotics fail to respond to conventional medical therapy and band ligation, necessitating alternative treatments including self-expanding metal stent (SEMS) placement for acute refractory esophageal variceal bleeding. In the present study, we carried out a systematic review and structured meta-analysis of all eligible studies to evaluate the technical feasibility, safety, clinical efficacy, and survival advantage of SEMS placement for the treatment of of acute esophageal variceal bleeding. METHODS: Searches of PubMed, EMBASE, Web of Science, and the Cochrane Library databases were carried out through December 2015. Individual study proportions were transformed into a quantity using the Freeman-Tukey variant of the arcsine square root transformed proportion. Combined weighted proportions, and meta-regression were then determined. RESULTS: The search yielded 12 studies involving n = 155 patients included in our meta analysis. Pooled clinical success rate in achieving hemostasis within 24 h was 96% (95% CI, 0.90-1.00). Technical success for SEMS deployment endoscopically was achieved in 97% of patients (95% CI, 0.91-1.00). Total adverse events (including rebleeding after 48 h, ulceration, and stent migration) were shown in 36% of patients after SEMS placement (95% CI, 0.23-0.50). Pooled 30-day and 60-day survival rates were 68% (95% CI, 0.56-0.80) and 64% (95% CI, 0.48-0.78), respectively. CONCLUSION: This study demonstrated that esophageal SEMS placement is a technically feasible modality and highly efficacious in achieving hemostasis in acute esophageal variceal hemorrhage. PMID- 26845491 TI - Meeting the mental health needs of children and youth through integrated care: A systems and policy perspective. AB - The health home program established under the Affordable Care Act (2010) is derived from the medical home concept originated by the American Academy of Pediatrics in 1968 to provide a care delivery model for children with special health care needs. As applied to behavioral health, health homes or medical homes have become increasingly adult-focused models, with a primary goal of coordinating physical and behavioral health care. For children and youth with serious emotional disorders, health homes must go beyond physical and behavioral health care to connect with other child-focused sectors, such as education, child welfare, and juvenile justice. Each of these systems have a significant role in helping children meet health and developmental goals, and should be included in integrated approaches to care for children and youth. Health homes for young people should incorporate a continuum of care from health promotion to the prevention and treatment of disorders. The challenge for child- and youth-focused health homes is to integrate effective services and supports into the settings where young people naturally exist, drawing on the best evidence from mental health, physical medicine, and other fields. What may be needed is not a health home as currently conceptualized for adults, nor a traditional medical home, but a family- and child-centered coordinated care and support delivery system supported by health homes or other arrangements. This article sets out a health home framework for children and youth with serious mental health conditions and their families, examining infrastructure and service delivery issues. PMID- 26845493 TI - Substance use disorder patient privacy and comprehensive care in integrated health care settings. AB - The Affordable Care Act (ACA) expands health insurance coverage for substance use disorder (SUD) treatment, underscoring the value of improving SUD service integration in primarily physical health care settings. It is not yet known to what degree specialized privacy regulations-Code of Federal Regulations Title 42, Part 2 (42 CFR Part 2), in particular-will affect access to or the utilization and delivery of SUD treatment in primary care. In addition to exploring the emerging benefits and barriers that specialized confidentiality regulations pose to treatment in early adopting integrated health care settings, this article introduces and explicates 42 CFR Part 2 to support provider and administrator implementation of SUD privacy regulations in integrated settings. The authors also argue that, although intended to protect patients with SUD, special SUD information protection may inadvertently reinforce stigma against patients by purporting the belief that SUD is different from other health problems and must be kept private. In turn, this stigma may inhibit the delivery of comprehensive integrated care. PMID- 26845494 TI - Limits on same-day billing in Medicaid hinders integration of behavioral health into the medical home model. AB - The potential expansion of insurance coverage through the Patient Protection and Affordable Care Act of 2010 can facilitate the reduction of access barriers and improved quality for behavioral health care. More than 5 million of the newly insured are expected to have mental health and substance use disorders. In addition, state and federal efforts to integrate behavioral and medical health needs through patient-centered medical home models and innovations in payment strategies provide an unprecedented opportunity to use federal financial support to improve not only access to care, but also improve quality through active care coordination, use of interdisciplinary teams, colocating services, and engaging in warm hand-offs between providers in the same setting. These potential advances are hindered in 24 different states because of Medicaid payment policy, with 7 explicitly limiting the ability to reimburse for physical health and behavioral health services on the same day for all providers. Without the ability for providers to be reimbursed for different services on the same day to improve behavioral and medical health care coordination, these states could be limited in their ability to improve care via patient-centered approaches and interdisciplinary team-based care that would involve physicians, clinical psychologists, psychiatrists, and other mental health professionals. Limits on same-day billing in Medicaid programs could impact up to 36.7 million people in 24 states, which is approximately 52.6% of all Medicaid enrollees. PMID- 26845492 TI - Faith-based organizations and the Affordable Care Act: Reducing Latino mental health care disparities. AB - The Patient Protection and Affordable Care Act (ACA; 2010) is expected to increase access to mental health care through provisions aimed at increasing health coverage among the nation's uninsured, including 10.2 million eligible Latino adults. The ACA will increase health coverage by expanding Medicaid eligibility to individuals living below 138% of the federal poverty level, subsidizing the purchase of private insurance among individuals not eligible for Medicaid, and requiring employers with 50 or more employees to offer health insurance. An anticipated result of this landmark legislation is improvement in the screening, diagnosis, and treatment of mental disorders in racial/ethnic minorities, particularly for Latinos, who traditionally have had less access to these services. However, these efforts alone may not sufficiently ameliorate mental health care disparities for Latinos. Faith-based organizations (FBOs) could play an integral role in the mental health care of Latinos by increasing help seeking, providing religion-based mental health services, and delivering supportive services that address common access barriers among Latinos. Thus, in determining ways to eliminate Latino mental health care disparities under the ACA, examining pathways into care through the faith-based sector offers unique opportunities to address some of the cultural barriers confronted by this population. We examine how partnerships between FBOs and primary care patient centered health homes may help reduce the gap of unmet mental health needs among Latinos in this era of health reform. We also describe the challenges FBOs and primary care providers need to overcome to be partners in integrated care efforts. PMID- 26845495 TI - Marginal Gap of Milled versus Cast Gold Restorations. AB - PURPOSE: This in vitro study evaluated and compared the vertical marginal gap of cast and milled full coverage gold copings using two margin designs (chamfer and chamfer bevel) before and after fitting adjustments. MATERIALS AND METHODS: Ten impressions were made of two metal master dies (one chamfer margin, one chamfer bevel margin) and poured twice in Type IV stone. The 20 subsequent casts with 40 dies were split into four groups (n = 10); cast gold bevel, cast gold chamfer, milled gold bevel, and milled gold chamfer groups. The cast specimens received approximately 40 MUm die relief no closer than 1 mm from the finish line. Cast copings were hand waxed, cast in a high noble gold alloy, chemically divested, and the sprues were removed. For milled gold copings, casts were scanned and copings designed using 3shape D900 scanner and software. Parameters were set to approximate analog fabrication (cement gap = 0.01 mm; extra cement gap = 0.04 mm, drill radius = 0.65 mm). Copings were milled from the same high noble alloy. All copings were seated on their respective master die in a custom scanning jig and measured using a measuring microscope at 90* (60 measurements per specimen, 15 per surface). Following initial measurements, all copings were adjusted on stone dies. The number of adjustment cycles was recorded and post-adjustment measurements were made using the same method. Data were analyzed using independent and paired t-tests. RESULTS: Milled gold copings with a beveled margin (11.7 +/- 20.4 MUm) had a significantly (p < 0.05) smaller marginal gap than cast gold copings with a beveled margin (43.6 +/- 46.8 MUm) after adjustment. Cast gold copings with a chamfer margin (22.7 +/- 24.7 MUm) had a significantly (p < 0.05) smaller marginal gap than milled gold copings with a chamfer margin (27.9 +/- 31.6 MUm) following adjustments. Adjustments significantly decreased marginal gap for both cast groups (p < 0.05) and the milled chamfer bevel group (p < 0.05) but had no significant effect on the milled chamfer group. CONCLUSIONS: Within the limitations of this study, results indicate that gold restorations milled with the tested parameters provide a vertical marginal gap that is an acceptable alternative to traditional gold crown casting techniques. PMID- 26845496 TI - Recurrent Proximal Femur Fractures in a Teenager With Osteogenesis Imperfecta on Continuous Bisphosphonate Therapy: Are We Overtreating? AB - Long-term bisphosphonate (BP) therapy in adults with osteoporosis is associated with atypical femoral fractures, caused by increased material bone density and prolonged suppression of bone remodeling which may reduce fracture toughness. In children with osteogenesis imperfecta (OI), long-term intravenous BP therapy improves bone structure and mass without further increasing the already hypermineralized bone matrix, and is generally regarded as safe. Here we report a teenage girl with OI type IV, who was started on cyclical intravenous pamidronate therapy at age 6 years because of recurrent fractures. Transiliac bone biopsy revealed classical structural features of OI but unusually low bone resorption surfaces. She made substantial improvements in functional ability, bone mass, and fracture rate. However, after 5 years of pamidronate therapy she started to develop recurrent, bilateral, nontraumatic, and proximal femur fractures, which satisfied the case definition for atypical femur fractures. Some fractures were preceded by periosteal reactions and prodromal pain. Pamidronate was discontinued after 7 years of therapy, following which she sustained two further nontraumatic femur fractures, and continued to show delayed tibial osteotomy healing. Despite rodding surgery, and very much in contrast to her affected, untreated, and normally mobile mother, she remains wheelchair-dependent. The case of this girl raises questions about the long-term safety of BP therapy in some children, in particular about the risk of oversuppressed bone remodeling with the potential for microcrack accumulation, delayed healing, and increased stiffness. The principal concern is whether there is point at which benefit from BP therapy could turn into harm, where fracture risk increases again. This case should stimulate debate whether current adult atypical femoral fracture guidance should apply to children, and whether low-frequency, low-dose cyclical, intermittent, or oral treatment maintenance regimens should be considered on a case-by-case basis. (c) 2016 American Society for Bone and Mineral Research. PMID- 26845497 TI - What Is the Price of Altruism? PMID- 26845498 TI - Socioeconomic gradients between locally transplanted and exported liver donors and recipients. PMID- 26845500 TI - Time vs. Money: A Quantitative Evaluation of Monitoring Frequency vs. Monitoring Duration. AB - The National Research Council has estimated that over 126,000 contaminated groundwater sites are unlikely to achieve low ug/L clean-up goals in the foreseeable future. At these sites, cost-effective, long-term monitoring schemes are needed in order to understand the long-term changes in contaminant concentrations. Current monitoring optimization schemes rely on site-specific evaluations to optimize groundwater monitoring frequency. However, when using linear regression to estimate the long-term zero-order or first-order contaminant attenuation rate, the effect of monitoring frequency and monitoring duration on the accuracy and confidence for the estimated attenuation rate is not site specific. For a fixed number of monitoring events, doubling the time between monitoring events (e.g., changing from quarterly monitoring to semi-annual monitoring) will double the accuracy of estimated attenuation rate. For a fixed monitoring frequency (e.g., semi-annual monitoring), increasing the number of monitoring events by 60% will double the accuracy of the estimated attenuation rate. Combining these two factors, doubling the time between monitoring events (e.g., quarterly monitoring to semi-annual monitoring) while decreasing the total number of monitoring events by 38% will result in no change in the accuracy of the estimated attenuation rate. However, the time required to collect this dataset will increase by 25%. Understanding that the trade-off between monitoring frequency and monitoring duration is not site-specific should simplify the process of optimizing groundwater monitoring frequency at contaminated groundwater sites. PMID- 26845499 TI - Triacylglycerol Metabolism, Function, and Accumulation in Plant Vegetative Tissues. AB - Oils in the form of triacylglycerols are the most abundant energy-dense storage compounds in eukaryotes, and their metabolism plays a key role in cellular energy balance, lipid homeostasis, growth, and maintenance. Plants accumulate oils primarily in seeds and fruits. Plant oils are used for food and feed and, increasingly, as feedstocks for biodiesel and industrial chemicals. Although plant vegetative tissues do not accumulate significant levels of triacylglycerols, they possess a high capacity for their synthesis, storage, and metabolism. The development of plants that accumulate oil in vegetative tissues presents an opportunity for expanded production of triacylglycerols as a renewable and sustainable bioenergy source. Here, we review recent progress in the understanding of triacylglycerol synthesis, turnover, storage, and function in leaves and discuss emerging genetic engineering strategies targeted at enhancing triacylglycerol accumulation in biomass crops. Such plants could potentially be modified to produce oleochemical feedstocks or nutraceuticals. PMID- 26845501 TI - Hydrogen-rich water ameliorates bronchopulmonary dysplasia (BPD) in newborn rats. AB - Bronchopulmonary dysplasia (BPD) is characterized by developmental arrest of the alveolar tissue. Oxidative stress is causally associated with development of BPD. The effects of hydrogen have been reported in a wide range of disease models and human diseases especially caused by oxidative stress. We made a rat model of BPD by injecting lipopolysaccharide (LPS) into the amniotic fluid at E16.5. The mother started drinking hydrogen-rich water from E9.5 and also while feeding milk. Hydrogen normalized LPS-induced abnormal enlargement of alveoli at P7 and P14. LPS increased staining for nitrotyrosine and 8-OHdG of the lungs, and hydrogen attenuated the staining. At P1, LPS treatment decreased expressions of genes for FGFR4, VEGFR2, and HO-1 in the lungs, and hydrogen increased expressions of these genes. In contrast, LPS treatment and hydrogen treatment had no essential effect on the expression of SOD1. Inflammatory marker proteins of TNFalpha and IL-6 were increased by LPS treatment, and hydrogen suppressed them. Treatment of A549 human lung adenocarcinoma epithelial cells with 10% hydrogen gas for 24 hr decreased production of reactive oxygen species in both LPS-treated and untreated cells. Lack of any known adverse effects of hydrogen makes hydrogen a promising therapeutic modality for BPD. Pediatr Pulmonol. 2016; 51:928-935. (c) 2016 Wiley Periodicals, Inc. PMID- 26845502 TI - A New Robust Estimator of Polydispersity from Dynamic Light Scattering Data. AB - We introduce a new estimator of particle size polydispersity for dynamic light scattering data, which quantifies the relative width of the intensity-weighted distribution of diffusion coefficients. Simulated dynamic light scattering data are analyzed to (i) compare the accuracy and precision of the new polydispersity indicator to polydispersity measurements from standard cumulant and moment analysis (MA) fits and (ii) establish for each method the optimum data range for fitting. Although MA is preferable at low polydispersity, the new estimator is the most accurate and precise at intermediate and large polydispersities. Finally, we successfully apply the method proposed here to real data from colloidal particles, microgels, and polymer solutions. PMID- 26845503 TI - Infants' generalizations about other people's emotions: Foundations for trait like attributions. AB - Adults often attribute internal dispositions to other people and down-play situational factors as explanations of behavior. A few studies have addressed the origins of this proclivity, but none has examined emotions, which rank among the more important dispositions that we attribute to others. Two experiments (N = 270) explored 15-month-old infants' predictive generalizations about other people's emotions. In exposure trials, infants watched an adult (Experimenter) perform actions on a series of objects and observed another adult (Emoter) react with either anger or neutral affect. Infants were then handed the objects to test whether they would imitate the Experimenter's actions. One chief novelty of the study was the inclusion of a generalization trial, in which the Experimenter performed a novel act on a novel object. We systematically manipulated whether the Emoter did or did not respond angrily to this novel demonstration, and whether the Emoter watched the infant's response. Even when no further emotional information was presented in the generalization trial, infants were still hesitant to perform the act when the previously angry Emoter was watching them. Infants tracked the Emoter's affective behavior and, based on her emotional history, they predicted that she would become angry again if she saw them perform a novel act. Making predictive generalizations of this type may be a precursor to more mature trait-like attributions about another person's emotional dispositions. PMID- 26845504 TI - Theory of mind and executive function in Chinese preschool children. AB - Cross-cultural research on children's theory of mind (ToM) understanding has raised questions about its developmental sequence and relationship with executive function (EF). The current study examined how ToM develops (using the tasks from Wellman & Liu, 2004) in relation to 2 EF skills (conflict inhibition, working memory) in 997 Chinese preschoolers (ages 3, 4, 5) in Chengdu, China. Compared with prior research with other Chinese and non-Chinese children, some general patterns in development were replicated in this sample. However, the children showed culture-specific reversals in the developmental sequence of ToM. For example, Chengdu children performed differently on the 2 false-belief tasks that were thought to be equivalent. Furthermore, conflict inhibition as well as working memory uniquely predicted ToM performance. We discuss the issues of ToM development as they relate to test items and cross-cultural--and subcultural- differences. PMID- 26845505 TI - Statistical treatment of looking-time data. AB - Looking times (LTs) are frequently measured in empirical research on infant cognition. We analyzed the statistical distribution of LTs across participants to develop recommendations for their treatment in infancy research. Our analyses focused on a common within-subject experimental design, in which longer looking to novel or unexpected stimuli is predicted. We analyzed data from 2 sources: an in-house set of LTs that included data from individual participants (47 experiments, 1,584 observations), and a representative set of published articles reporting group-level LT statistics (149 experiments from 33 articles). We established that LTs are log-normally distributed across participants, and therefore, should always be log-transformed before parametric statistical analyses. We estimated the typical size of significant effects in LT studies, which allowed us to make recommendations about setting sample sizes. We show how our estimate of the distribution of effect sizes of LT studies can be used to design experiments to be analyzed by Bayesian statistics, where the experimenter is required to determine in advance the predicted effect size rather than the sample size. We demonstrate the robustness of this method in both sets of LT experiments. PMID- 26845506 TI - Children's reasoning about distributive and retributive justice across development. AB - Research on distributive justice indicates that preschool-age children take issues of equity and merit into account when distributing desirable items, but that they often prefer to see desirable items allocated equally in third-party tasks. By contrast, less is known about the development of retributive justice. In a study with 4- to 10-year-old children (n = 123) and adults (n = 93), we directly compared the development of reasoning about distributive and retributive justice. We measured the amount of rewards or punishments that participants allocated to recipients who differed in the amount of good or bad things they had done. We also measured judgments about collective rewards and punishments. We found that the developmental trajectory of thinking about retributive justice parallels that of distributive justice. The 4- to 5-year-olds were the most likely to prefer equal distributions of both rewarding and aversive consequences; older children and adults preferred deservingness-based allocations. The 4- to 5 year-olds were also most likely to judge collective rewards and punishments as fair; this tendency declined with increasing age. Our results also highlight the extent to which the notion of desert influences thinking about distributive and retributive justice; desert was considered equally when participants allocated reward and punishments, but in judgments about collective discipline, participants focused more on desert in cases of punishment compared with reward. We discuss our results in relation to theories about preferences for equality versus equity, theories about how desert is differentially weighed across distributive and retributive justice, and the literature on moral development and fairness. PMID- 26845507 TI - Developmental regulation with progressive vision loss: Use of control strategies and affective well-being. AB - The present study addresses older adults' developmental regulation when faced with progressive and irreversible vision loss. We used the motivational theory of life span development as a conceptual framework and examined changes in older adults' striving for control over everyday goal achievement, and their association with affective well-being, in a sample of 364 older adults diagnosed with age-related macular degeneration. Using longitudinal data from 5 occasions at 6-month intervals, we examined intraindividual change in control strategies, and how it was related to change in affective well-being, in terms of self-rated happiness and depressive symptoms. Mixed model analyses confirmed our hypotheses that (a) intraindividual change, particularly in selective primary control and in compensatory secondary control (CSC), predict change toward higher happiness ratings and lower depression; and (b) as functional abilities (instrumental activities of daily living) declined, CSC became increasingly predictive of better affective well-being. Overall, the findings suggest that CSC strategies are essential for maintaining affective well-being when physical functioning declines. Intensified selective primary control striving may be effective to achieve goals that have become difficult to reach but are not associated with affective well-being, possibly because struggling with difficulties undermines the experience of enjoyable mastery. In contrast, goal adjustments and self protective thinking may help to find pleasure even from restricted daily activities. PMID- 26845508 TI - Forster Resonance Energy Transfer-Based Self-Assembled Nanoprobe for Rapid and Sensitive Detection of Postoperative Pancreatic Fistula. AB - Postoperative pancreatic fistula (POPF) is the most serious and challenging complication following gastroenterological surgery. Activated pancreatic juice leaking from the organ remnant contains proteases that attack the surrounding tissue, potentially leading to severe inflammation, tissue necrosis, and fistula formation. However, it is difficult to observe pancreatic leakage during surgery and to evaluate the protease activity of leaked fluid at the patient's bedside. This report describes a protein nanocage-based protease ratiometric sensor comprising a pancreatic protease-sensitive small heat-shock protein (HSP) 16.5, which is a naturally occurring protein in Methanococcus jannaschii that forms a spherical structure by self-assembly of 24 subunits, and a chemically conjugated donor-acceptor dye pair for Forster resonance energy transfer (FRET). The HSP FRET probe was constructed by subunit exchange of each dye-labeled engineered HSP, resulting in a spherical nanocage of approximately 10 nm in diameter, which exhibited very high stability against degradation in blood plasma and no remarkable toxicity in mice. The efficiency of FRET was found to depend on both the dye orientation and the acceptor/donor ratio. Pancreatic proteases, including trypsin, alpha-chymotrypsin, and elastase, were quantitatively analyzed by fluorescence recovery with high specificity using the HSP-FRET nanoprobe. Furthermore, the HSP-FRET nanoprobe was sufficiently sensitive to detect POPF in the pancreatic juice of patients using only the naked eye within 10 min. Thus, this novel nanoprobe is proposed as an effective and convenient tool for the detection of POPF and the visualization of activated pancreatic juice during gastroenterological surgery. PMID- 26845509 TI - Meta-analysis requires independent observations and freedom from bias. PMID- 26845510 TI - Implicit Time Integration for Multiscale Molecular Dynamics Using Transcendental Pade Approximants. AB - Molecular dynamics systems evolve through the interplay of collective and localized disturbances. As a practical consequence, there is a restriction on the time step imposed by the broad spectrum of time scales involved. To resolve this restriction, multiscale factorization was introduced for molecular dynamics as a method that exploits the separation of time scales by coevolving the coarse grained and atom-resolved states via Trotter factorization. Developing a stable time-marching scheme for this coevolution, however, is challenging because the coarse-grained dynamical equations depend on the microstate; therefore, these equations cannot be expressed in closed form. The objective of this paper is to develop an implicit time integration scheme for multiscale simulation of large systems over long periods of time and with high accuracy. The scheme uses Pade approximants to account for both the stochastic and deterministic features of the coarse-grained dynamics. The method is demonstrated for a protein either undergoing a conformational change or migrating under the influence of an external force. The method shows promise in accelerating multiscale molecular dynamics without a loss of atomic precision or the need to conjecture the form of coarse-grained governing equations. PMID- 26845511 TI - Electrophilicities and Protein Covalent Binding of Demethylation Metabolites of Colchicine. AB - Colchicine, an alkaloid existing in plants of Liliaceous colchicum, has been widely used in the treatment of gout and familial Mediterranean fever. The administration of colchicine was found to cause liver injury in humans. The mechanisms of colchicine-induced liver toxicity remain unknown. The objectives of this study were to determine the electrophilicities of demethylation metabolites of colchicine and investigate the protein adductions derived from the reactive metabolites of colchicine. Four demethylated colchicine (1-, 2-, 3-, and 10 DMCs), namely, M1-M4, were detected in colchicine-fortified microsomal incubations. Four N-acetyl cysteine (NAC) conjugates (M5-M8) derived from colchicine were detected in the microsomes in the presence of NAC. M5 and M6 were derived from 10-DMC. M7 resulted from the reaction of 2-DMC or 3-DMC with NAC, and M8 originated from 10-DMC. Microsomal protein covalent binding was observed after exposure to colchicine. Two cysteine adducts (CA-1 and CA-2) derived from 10-DMC were found in proteolytically digested microsomal protein samples after incubation with colchicine. The findings allow us to define the chemical property of demethylation metabolites of colchicine and the interaction between protein and the reactive metabolites of colchicine generated in situ. PMID- 26845512 TI - The Effect of Substituents at Lewis Acidic Bismuth(III) Centers on Its Propensity to Bind a Noble Metal Donor. AB - To investigate the effect of X in ambiphilic compounds BiX(o-PPh2-C6H4)2, PBiP-X, on metallophilic Pt-Bi interactions in its PtCl2 complexes two new derivatives PBiP-Me and PBiP-C6F5 were synthesized. Reaction with dichloro(1,5 cyclooctadiene)platinum(II) led to the platinum(II) complexes [PtCl2(PBiP-Me)], 3, and [PtCl2(PBiP-C6F5)], 4, which together with the halide [PtCl2(PBiP-Cl)], 2, reported previously, establish a series of related PBiP-X complexes differing only in X. This could be complemented by accessing [PtCl2(PBiP-OTf)], 5, through the reaction of 2 with AgOTf. Analysis of the geometrical and electronic structures of these complexes revealed that in all cases the platinum(II) centers act as donors (through their filled d(z(2)) orbitals) to the bismuth(III) centers (possessing sigma*(Bi-X)/6p acceptor orbitals). The strength of these interactions increases with increasing electron-withdrawing character of X, which supports the conceptual approach in constructing this new class of compounds. PMID- 26845513 TI - TOTALL: high cost of allergic rhinitis-a national Swedish population-based questionnaire study. AB - Allergic rhinitis is a global illness with a well-recognised impact on quality of life and work performance. Comparatively little is known about the extent of its economic impact on society. The TOTALL study estimates the total cost of allergic rhinitis using a sample representing the entire Swedish population of working age. A questionnaire focused on allergic rhinitis was mailed out to a random population of Swedish residents, aged 18-65 years. Health-care contacts, medications, absenteeism (absence from work) and presenteeism (reduced working capacity at work) were assessed, and the direct and indirect costs of allergic rhinitis were calculated. Medication use was evaluated in relation to the ARIA guidelines. In all, 3,501 of 8,001 (44%) answered the questionnaire, and 855 (24%) of these reported allergic rhinitis. The mean annual direct and indirect costs because of allergic rhinitis were ?210.3 and ?750.8, respectively, resulting in a total cost of ?961.1 per individual/year. Presenteeism represented 70% of the total cost. Antihistamines appear to be used in excess in relation to topical steroids, and the use of nasal decongestants was alarmingly high. The total cost of allergic rhinitis in Sweden, with a population of 9.5 million, was estimated at ?1.3 billion annually. These unexpectedly high costs could be related to the high prevalence of disease, in combination with the previously often underestimated indirect costs. Improved adherence to guidelines might ease the economic burden on society. PMID- 26845515 TI - Self-Assembled Gold Nanoclusters for Bright Fluorescence Imaging and Enhanced Drug Delivery. AB - Nanoparticles combining enhanced cellular drug delivery with efficient fluorescence detection are important tools for the development of theranostic agents. Here, we demonstrate this concept by a simple, fast, and robust protocol of cationic polymer-mediated gold nanocluster (Au NCs) self-assembly into nanoparticles (NPs) of ca. 120 nm diameter. An extensive characterization of the monodisperse and positively charged NPs revealed pH-dependent swelling properties, strong fluorescence enhancement, and excellent colloidal and photostability in water, buffer, and culture medium. The versatility of the preparation is demonstrated by using different Au NC surface ligands and cationic polymers. Steady-state and time-resolved fluorescence measurements give insight into the aggregation-induced emission phenomenon (AIE) by tuning the Au NC interactions in the self-assembled nanoparticles using the pH-dependent swelling. In vitro studies in human monocytic cells indicate strongly enhanced uptake of the NPs compared to free Au NCs in endocytic compartments. The NPs keep their assembly structure with quite low cytotoxicity up to 500 MUg Au/mL. Enhanced drug delivery is demonstrated by loading peptides or antibodies in the NPs using a one pot synthesis. Fluorescence microscopy and flow cytometry confirmed intracellular colocalization of the biomolecules and the NP carriers with a respective 1.7-fold and 6.5-fold enhanced cellular uptake of peptides and antibodies compared to the free biomolecules. PMID- 26845516 TI - Hepatic mitochondrial dysfunction in nonalcoholic steatohepatitis: Read-out or reason? PMID- 26845517 TI - Diffuse Malignant Peritoneal Mesothelioma Presenting with Psammomatous Calcification on a Cervical Smear. AB - BACKGROUND: Psammoma bodies in cervical smears are rare but may be associated with benign and malignant diseases of the female genital tract. CASE: A 52-year old nulliparous woman presented with a 2-month history of intermittent vaginal spotting and post-coital bleeding. A cervical smear showed an inconclusive high grade glandular lesion with psammomatous calcification. Previous cervical smears had been normal. This smear contained papillary tissue fragments, occasional spheres of gland-like cells and frequent psammoma bodies. The patient underwent a laparoscopic hysterectomy, bilateral salpingo-oophorectomy and omentectomy. The surface of the omentum and both ovaries contained psammoma bodies with groups of cells identical to those in the cervical smear. Within the omentum, there were invasive malignant epithelioid cells positive for CK7, CK5/6, calretinin, D2-40, WT-1, CK5/6, p16 and EMA. Desmin and PAX-8 immunostains were negative. There was also evidence of BRCA1-associated protein 1 (BAP1) dysfunction compatible with diffuse malignant peritoneal mesothelioma (DMPM). CONCLUSION: We describe the first reported case of DMPM presenting with an abnormal cervical smear, a rare but important differential diagnosis to consider in abnormal cervical smears showing psammomatous calcification. PMID- 26845518 TI - A complete inorganic colour converter based on quantum-dot-embedded silicate glasses for white light-emitting-diodes. AB - A complete inorganic quantum dot color converter for a white LED is achieved using silicate-based quantum-dot-embedded glasses (QDEGs). The white LED exhibits a high CRI of 90 and highly improved thermal stability up to 200 degrees C, demonstrating its robustness and practicality. The CdSe/CdS core/shell structure within the silicate glass is expected to enhance the colour converting efficiency. PMID- 26845514 TI - Therapeutics Targeting Protein Acetylation Perturb Latency of Human Viruses. AB - Persistent viral infections are widespread and represent significant public health burdens. Some viruses endure in a latent state by co-opting the host epigenetic machinery to manipulate viral gene expression. Small molecules targeting epigenetic pathways are now in the clinic for certain cancers and are considered as potential treatment strategies to reverse latency in HIV-infected individuals. In this review, we discuss how drugs interfering with one epigenetic pathway, protein acetylation, perturb latency of three families of pathogenic human viruses-retroviruses, herpesviruses, and papillomaviruses. PMID- 26845519 TI - Clashing Diagnostic Approaches: DSM-ICD Versus RDoC. AB - Since at least the middle of the past century, one overarching model of psychiatric classification has reigned supreme, namely, that of the Diagnostic and Statistical Manual of Mental Disorders and the International Statistical Classification of Diseases and Related Health Problems (herein referred to as DSM ICD). This DSM-ICD approach embraces an Aristotelian view of mental disorders as largely discrete entities that are characterized by distinctive signs, symptoms, and natural histories. Over the past several years, however, a competing vision, namely, the Research Domain Criteria (RDoC) initiative launched by the National Institute of Mental Health, has emerged in response to accumulating anomalies within the DSM-ICD system. In contrast to DSM-ICD, RDoC embraces a Galilean view of psychopathology as the product of dysfunctions in neural circuitry. RDoC appears to be a valuable endeavor that holds out the long-term promise of an alternative system of mental illness classification. We delineate three sets of pressing challenges--conceptual, methodological, and logistical/pragmatic--that must be addressed for RDoC to realize its scientific potential. We conclude with a call for further research, including investigation of a rapprochement between Aristotelian and Galilean approaches to psychiatric classification. PMID- 26845521 TI - Synthetic Method for Oligonucleotide Block by Using Alkyl-Chain-Soluble Support. AB - A straightforward method for the synthesis of oligonucleotide blocks using a Cbz type alkyl-chain-soluble support (Z-ACSS) attached to the 3'-OH group of 3' terminal nucleosides was developed. The Z-ACSS allowed for the preparation of fully protected deoxyribo- and ribo-oligonucleotides without chromatographic purification and released dimer- to tetramer-size oligonucleotide blocks via hydrogenation using a Pd/C catalyst without significant loss or migration of protective groups such as 5'-end 4,4'-dimethoxtrityl, 2-cyanoethyl on internucleotide bonds, or 2'-TBS. PMID- 26845520 TI - Vital Signs: Alcohol-Exposed Pregnancies--United States, 2011-2013. AB - BACKGROUND: Alcohol is a teratogen.* Prenatal alcohol exposure is associated with a range of adverse reproductive outcomes and can cause fetal alcohol spectrum disorders (FASDs) characterized by lifelong physical, behavioral, and intellectual disabilities. FASDs are completely preventable if a woman does not drink alcohol while pregnant. METHODS: CDC analyzed data from the 2011-2013 National Survey of Family Growth to generate U.S. prevalence estimates of risk for an alcohol-exposed pregnancy for 4,303 nonpregnant, nonsterile women aged 15 44 years, by selected demographic and behavioral factors. A woman was considered at risk for an alcohol-exposed pregnancy during the past month if she had sex with a male, drank any alcohol, and did not (and her partner did not with her) use contraception in the past month; was not sterile; and had a partner (or partners) not known to be sterile. RESULTS: The weighted prevalence of alcohol exposed pregnancy risk among U.S. women aged 15-44 years was 7.3%. During a 1 month period, approximately 3.3 million women in the United States were at risk for an alcohol-exposed pregnancy. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Alcohol use in pregnancy is associated with low birthweight, preterm birth, birth defects, and developmental disabilities. Women of reproductive age should be informed of the risks of alcohol use during pregnancy, and contraception should be recommended, as appropriate, for women who do not want to become pregnant. Women wanting a pregnancy should be advised to stop drinking at the same time contraception is discontinued. Health care providers should advise women not to drink at all if they are pregnant or there is any chance they might be pregnant. Alcohol misuse screening and behavioral counseling (also known as alcohol screening and brief intervention) is recommended for all adults in primary care, including reproductive-aged and pregnant women, as an evidenced based approach to reducing alcohol consumption among persons who consume alcohol in excess of the recommended guidelines. PMID- 26845522 TI - Recombinational branch migration by the RadA/Sms paralog of RecA in Escherichia coli. AB - RadA (also known as 'Sms') is a highly conserved protein, found in almost all eubacteria and plants, with sequence similarity to the RecA strand exchange protein and a role in homologous recombination. We investigate here the biochemical properties of the E. coli RadA protein and several mutant forms. RadA is a DNA-dependent ATPase, a DNA-binding protein and can stimulate the branch migration phase of RecA-mediated strand transfer reactions. RadA cannot mediate synaptic pairing between homologous DNA molecules but can drive branch migration to extend the region of heteroduplex DNA, even without RecA. Unlike other branch migration factors RecG and RuvAB, RadA stimulates branch migration within the context of the RecA filament, in the direction of RecA-mediated strand exchange. We propose that RadA-mediated branch migration aids recombination by allowing the 3' invading strand to be incorporated into heteroduplex DNA and to be extended by DNA polymerases. PMID- 26845523 TI - Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling. AB - Endothelial cells respond to molecular and physical forces in development and vascular homeostasis. Deregulation of endothelial responses to flow-induced shear is believed to contribute to many aspects of cardiovascular diseases including atherosclerosis. However, how molecular signals and shear-mediated physical forces integrate to regulate vascular patterning is poorly understood. Here we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/Wnt11 renders endothelial cells more sensitive to shear, resulting in axial polarization and migration against flow at lower shear levels. Integration of flow modelling and polarity analysis in entire vascular networks demonstrates that polarization against flow is achieved differentially in artery, vein, capillaries and the primitive sprouting front. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus. PMID- 26845524 TI - Repetitive transcranial magnetic stimulation and transcranial direct-current stimulation in neuropathic pain due to radiculopathy: a randomized sham controlled comparative study. AB - No study has directly compared the effectiveness of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in neuropathic pain (NP). In this 2-centre randomised double-blind sham-controlled study, we compared the efficacy of 10-Hz rTMS and anodal 2-mA tDCS of the motor cortex and sham stimulation contralateral to the painful area (3 daily sessions) in patients with NP due to lumbosacral radiculopathy. Average pain intensity (primary outcome) was evaluated after each session and 5 days later. Secondary outcomes included neuropathic symptoms and thermal pain thresholds for the upper limbs. We used an innovative design that minimised bias by randomly assigning patients to 1 of 2 groups: active rTMS and tDCS or sham rTMS and tDCS. For each treatment group (active or sham), the order of the sessions was again randomised according to a crossover design. In total, 51 patients were screened and 35 (51% women) were randomized. Active rTMS was superior to tDCS and sham in pain intensity (F = 2.89 and P = 0.023). Transcranial direct-current stimulation was not superior to sham, but its analgesic effects were correlated to that of rTMS (P = 0.046), suggesting common mechanisms of action. Repetitive transcranial magnetic stimulation lowered cold pain thresholds (P = 0.04) and its effect on cold pain was correlated with its analgesic efficacy (P = 0.006). However, rTMS had no impact on individual neuropathic symptoms. Thus, rTMS is more effective than tDCS and sham in patients with NP due to lumbosacral radiculopathy and may modulate the sensory and affective dimensions of pain. PMID- 26845526 TI - Construction of tetranuclear metallacycles based on half-sandwich Ir, Rh fragments and pyridyl-substituted ligands with different coordinate vectors. AB - A series of organometallic macrocycles have been constructed by two-step reactions of [Cp*M(MU-Cl)Cl]2 (M = Ir, Rh), firstly with AgOTf to abstract chloride ions and then with simple pyridyl-substituted ligands pyridyldipyrromethene (HL(1)), pyridin-4-yl (1H-pyrrol-2-yl)methanone (HL(2)) and pyridine-4-carbohydrazide (HL(3))-resulting in the formation of the tetranuclear 32-membered metallacycles [(Cp*Ir)(L(1))]4(OTf)4 (2a) and [(Cp*Rh)(L(1))]4(OTf)4 (2b), and the 28-membered metallacycles [(Cp*Ir)(L(2))]4 (OTf)4 (3a), [(Cp*Rh)(L(2))]4(OTf)4 (3b), [(Cp*Ir)(L(3))]4(OTf)4 (4a) and [(Cp*Rh)(L(3))]4(OTf)4 (4b). Four target complexes were characterised by single crystal X-ray analyses, revealing that these metallacycles, constructed from half sandwich metal corners and pyridyl-substituted linkers, form large ring structures. The observed variation in the metallacyclic geometries was explained on the basis of the structural flexibility of the corner fragments, subtle changes in coordination geometries, and changes in the orientation of the coordinate vectors in the given ligands, as well as different dihedral angles between the two binding fragments in the nonplanar ligands. PMID- 26845525 TI - Problem-solving skills training for parents of children with chronic pain: a pilot randomized controlled trial. AB - This pilot randomized controlled trial aimed to determine the feasibility, acceptability, and preliminary efficacy of parental problem-solving skills training (PSST) compared with treatment as usual on improving parental mental health symptoms, physical health and well-being, and parenting behaviors. Effects of parent PSST on child outcomes (pain, emotional, and physical functioning) were also examined. Participants included 61 parents of children aged 10 to 17 years with chronic pain randomized to PSST (n = 31) or treatment as usual (n = 30) groups. Parents receiving PSST participated in 4 to 6 individual sessions of training in problem-solving skills. Outcomes were assessed at pretreatment, immediately after treatment, and at a 3-month follow-up. Feasibility was determined by therapy session attendance, therapist ratings, and parent treatment acceptability ratings. Feasibility of PSST delivery in this population was demonstrated by high compliance with therapy attendance, excellent retention, high therapist ratings of treatment engagement, and high parent ratings of treatment acceptability. PSST was associated with posttreatment improvements in parental depression (d = -0.68), general mental health (d = 0.64), and pain catastrophizing (d = -0.48), as well as in child depression (d = -0.49), child general anxiety (d = -0.56), and child pain-specific anxiety (d = -0.82). Several effects were maintained at the 3-month follow-up. Findings demonstrate that PSST is feasible and acceptable to parents of youths with chronic pain. Treatment outcome analyses show promising but mixed patterns of effects of PSST on parent and child mental health outcomes. Further rigorous trials of PSST are needed to extend these pilot results. PMID- 26845527 TI - Unbiased estimation of biomarker panel performance when combining training and testing data in a group sequential design. AB - Motivated by an ongoing study to develop a screening test able to identify patients with undiagnosed Sjogren's Syndrome in a symptomatic population, we propose methodology to combine multiple biomarkers and evaluate their performance in a two-stage group sequential design that proceeds as follows: biomarker data is collected from first stage samples; the biomarker panel is built and evaluated; if the panel meets pre-specified performance criteria the study continues to the second stage and the remaining samples are assayed. The design allows us to conserve valuable specimens in the case of inadequate biomarker panel performance. We propose a nonparametric conditional resampling algorithm that uses all the study data to provide unbiased estimates of the biomarker combination rule and the sensitivity of the panel corresponding to specificity of 1-t on the receiver operating characteristic curve (ROC). The Copas and Corbett (2002) correction, for bias resulting from using the same data to derive the combination rule and estimate the ROC, was also evaluated and an improved version was incorporated. An extensive simulation study was conducted to evaluate finite sample performance and propose guidelines for designing studies of this type. The methods were implemented in the National Cancer Institutes Early Detection Network Urinary PCA3 Evaluation Trial. PMID- 26845528 TI - Don't Praise Me, Don't Chase Me: Emotional Reactivity to Positive and Negative Social-Evaluative Videos in Patients With Borderline Personality Disorder. AB - Diagnostic criteria for borderline personality disorder (BPD) include interpersonal problems and high reactivity to negative social interactions. However, experimental studies on these symptoms are scarce, and it remains unclear whether reactivity is also altered in response to positive social interactions. To simulate such situations, the present study used videographic stimuli (E.Vids; Blechert, Schwitalla, & Wilhelm, 2013) in which actors express rejecting, neutral, or appreciating sentences. Twenty BPD patients and 20 healthy controls rated their emotional responses to these on pleasantness, arousal, and 11 specific emotions. In addition to elevated reactivity to negative E.Vids, patients with BPD showed marked reduction in pleasantness responses to positive E.Vids. Furthermore, they exhibited less pride, happiness, feelings of approval, and attraction/love in response to positive videos and more anger, anxiety, embarrassment, contempt, guilt, feelings of disapproval/rejection, and sadness to negative videos. Interestingly, BPD patients also reported negative emotions in response to positive videos. Implications for psychotherapy and research are discussed. PMID- 26845529 TI - Psychopathic Personality in the General Population: Differences and Similarities Across Gender. AB - This study aimed to identify distinct subgroups of adults in a general population sample (N = 2,500; 52.6% females) based on their scores on three psychopathy dimensions. Using latent profile analysis, five groups were identified among males and females separately, including a psychopathic personality group. Multivariate analyses of variance showed that this latter group had higher levels of aggression, offending, substance use, attention-deficit/hyperactivity symptoms, internalizing problems, and maltreatment than most of the other groups. Associated features of males and females with a psychopathic personality were very similar; however, salient gender differences did emerge. Specifically, females with a psychopathic personality were more frequently exposed to sexual abuse, expressed more emotional difficulties, and engaged in higher levels of relational aggression. In conclusion, person-oriented analyses identified adults with a personality that looks like psychopathy, and furthered our understanding of gender similarities and differences in these adults. PMID- 26845530 TI - A Multi-method Examination of the Links Between ADHD and Personality Disorder. AB - An existing relationship between attention-deficit/hyperactivity disorder (ADHD) and personality disorder (PD) has been well documented, yet research has been limited by possible selection and self-report biases as well as PD models of questionable validity. This study examined the relationship of ADHD with adult personality traits and disorders in a sample that included individuals prescreened for elevated childhood ADHD symptoms. Four hundred thirty-nine undergraduates completed retrospective reports of childhood ADHD symptoms as well as current ratings of ADHD symptoms, traditional PD categories, and the DSM-5 alternative PD trait model. To overcome potential biases in self-report, 161 parents of the participants provided ratings of childhood and current functioning. Results suggest that while self-report of ADHD was significantly correlated with several PDs, parent reports obtained somewhat more specific links with adult dependent, borderline, and paranoid PDs. Most importantly, the DSM-5 Section III dimensional trait model provided greater specificity, as the trait of distractibility consistently emerged as a unique predictor, and thus appeared more useful for understanding the developmental pathways of ADHD. PMID- 26845531 TI - The Mask of Sanity: Facial Expressive, Self-Reported, and Physiological Consequences of Emotion Regulation in Psychopathic Offenders. AB - This study investigated the physiological, self-reported, and facial correlates of emotion regulation in psychopathy. Specifically, we compared psychopathic offenders (n = 42), nonpsychopathic offenders (n = 42), and nonoffender controls (n = 26) in their ability to inhibit and express emotion while watching affective films (fear, happy, and sad). Results showed that all participants were capable of drastically diminishing facial emotions under inhibition instructions. Contrary to expectation, psychopaths were not superior in adopting such a "poker face." Further, the inhibition of emotion was associated with cardiovascular changes, an effect that was also not dependent on psychopathy (or its factors), suggesting emotion inhibition to be an effortful process in psychopaths as well. Interestingly, psychopathic offenders did not differ from nonpsychopaths in the capacity to show content-appropriate facial emotions during the expression condition. Taken together, these data challenge the view that psychopathy is associated with either superior emotional inhibitory capacities or a generalized impairment in showing facial affect. PMID- 26845533 TI - The Factor Structure of the Schizotypal Personality Questionnaire in Undergraduate and Community Samples. AB - The prevailing theoretical model of the Schizotypal Personality Questionnaire (SPQ) is a three-factor model based on subscale-level analyses. However, recent item-level factor analyses of the SPQ suggest a four- or five-factor model. To examine the factor structure of the SPQ and how this structure may differ between undergraduate and community samples, the authors conducted exploratory and confirmatory item-level factor analyses of this measure on undergraduate (N = 1,850) and community participants (N = 1,464). A clear three-factor solution was found in the community sample, whereas a somewhat equivocal four-factor solution was found in the undergraduate sample. Both structures displayed gender invariance. This is the first study to address the issues of undergraduate sample generalizability and gender invariance in an item-level exploratory factor analysis of the SPQ. Given the disparate findings in the samples, this study indicates the importance of using both community and undergraduate samples when examining the factor structure of the SPQ. PMID- 26845532 TI - Negative Urgency Accounts for the Association Between Borderline Personality Features and Intimate Partner Violence in Young Men. AB - Many studies have demonstrated that borderline personality disorder (BPD) is associated with aggression and, in particular, intimate partner violence; however, the mechanisms underlying this association have been less clearly identified. The present study examines the hypothesis that negative urgency (impulsive behavior in response to intense, negative emotions) may explain the specific association between BPD and intimate partner violence. Cross-sectional self-report measures of BPD, violent behavior, and multiple dimensions of impulsivity were administered to 193 undergraduate men. BPD profile scores were associated with both general violence behaviors and intimate partner violence; however, an indirect path via negative urgency existed only with intimate partner violence. No indirect paths from BPD scores were demonstrated via any other factors of impulsivity, although sensation seeking was an independent predictor of general violence. Clinical implications and directions for future research are discussed. PMID- 26845535 TI - Minilaparoscopic Versus Conventional Laparoscopic Sacrocolpopexy: A Comparative Study. AB - INTRODUCTION AND AIMS: We aim to compare clinical and surgical outcomes between minilaparoscopic sacrocolpopexy (MLSC) and conventional laparoscopic sacrocolpopexy (LSC). As far as we know, no comparative study exists between these two minimal invasive procedures to correct vaginal prolapse. DESIGN AND SETTING: An observational and comparative study with 20 individuals submitted to vaginal vault prolapse correction between June and December of 2014 in our tertiary referral unit. Nine women were submitted to 3-mm MLSC and the others were approached by a standard 5-mm laparoscopic technique. MATERIALS AND METHODS: Women's demographic data and prolapse grade were evaluated preoperatively using the Pelvic Organ Prolapse Quantification score. Operative parameters (surgical time, blood loss, and complications under Satava and Clavien-Dindo classification) and length of hospitalization were also compared. Postoperative pain and surgical scar satisfaction were measured using Visual Analog Pain Scale and Patient and Observer Scar Assessment Questionnaire, respectively. RESULTS: MLSC took approximately the same time as LSC (P > .05). No significant differences in operative time, blood loss, length of hospitalization, and complications (Satava, Clavien-Dindo) were observed between both groups. Pain score after surgery was similar in MLSC and LSC (P > .05). Surgical scar monitoring at 3 months established that MLSC produced better overall results than LSC (P < .05). Anatomic cure rate was 100%. CONCLUSION: Minilaparoscopy is a feasible and attractive approach for sacrocolpopexy as it enhances cosmetics, keeping the low morbidity associated with the classical laparoscopic approaches. PMID- 26845534 TI - Wildtype adult stem cells, unlike tumor cells, are resistant to cellular damages in Drosophila. AB - Adult stem cells or residential progenitor cells are critical to maintain the structure and function of adult tissues (homeostasis) throughout the lifetime of an individual. Mis-regulation of stem cell proliferation and differentiation often leads to diseases including cancer, however, how wildtype adult stem cells and cancer cells respond to cellular damages remains unclear. We find that in the adult Drosophila midgut, intestinal stem cells (ISCs), unlike tumor intestinal cells, are resistant to various cellular damages. Tumor intestinal cells, unlike wildtype ISCs, are easily eliminated by apoptosis. Further, their proliferation is inhibited upon autophagy induction, and autophagy-mediated tumor inhibition is independent of caspase-dependent apoptosis. Interestingly, inhibition of tumorigenesis by autophagy is likely through the sequestration and degradation of mitochondria, as compromising mitochondria activity in these tumor models mimics the induction of autophagy and increasing the production of mitochondria alleviates the tumor-suppression capacity of autophagy. Together, these data demonstrate that wildtype adult stem cells and tumor cells show dramatic differences in sensitivity to cellular damages, thus providing potential therapeutic implications targeting tumorigenesis. PMID- 26845536 TI - Resveratrol induces intracellular Ca(2+) rise via T-type Ca(2+) channels in a mesothelioma cell line. AB - AIMS: Intracellular calcium (Ca(2+)) is known to play an important role in cancer development and growth. Resveratrol (Res) is a stilbene polyphenol occurring in several plant species and known for various possible beneficial effects, including its ability to inhibit proliferation and to induce apoptosis in cancer cells. This study was designed to determine whether Res affects Ca(2+) signaling in cancer cells. MAIN METHODS: We used the REN human mesothelioma cell line, as an in vitro cancer cell model, and the non-malignant human mesothelial MeT5A cell line, as normal cell model. Cytosolic Ca(2+) concentration was measured by the fluorescent indicator Fura-2. Immunofluorescence, Western blot, and siRNA technique were employed to assess the involvement of T-type Ca(2+) channels. Cell viability was determined by the calcein assay. KEY FINDINGS: REN cells transiently exposed to 1-10MUM Res showed increasing peaks of Ca(2+) that were absent in Ca(2+)-free medium and were reduced by non-selective (Ni(2+)), and highly selective (NNC 55-0396) T-type Ca(2+) channels antagonist, and by siRNA knockout of Cav3.2T-type Ca(2+) channel gene. Dose-dependent curve of Res-induced Ca(2+) peaks showed a rightward shift in normal MeT-5A mesothelial cells (EC50=4.9MUM) with respect to REN cells (EC50=2.7MUM). Moreover, incubation with 3 and 10MUM Res for 7days resulted in cell growth inhibition for REN, but not for MeT-5A cells. SIGNIFICANCE: Res induces Ca(2+) influx, possibly mediated through T-type Ca(2+) channels, with significant selectivity towards mesothelioma cells, suggesting a possible use as an adjuvant to chemotherapy drugs for mesothelioma clinical treatment. PMID- 26845537 TI - Endovascular treatment of complex abdominal and thoracoabdominal type IV aortic aneurysms with fenestrated technology. AB - The establishment use of fenestrated and branched devices to treat complex aortic aneurysms as a first-line management option has been previously reported. This article reviews the current literature of the use of fenestrated devices to treat complex abdominal and thoracoabdominal type IV aortic aneurysms as a first-line management option. A literature search was performed. This review particularly focuses on all the aspects of the use and results of fenestrated stent-grafts (SGs) in patients with complex abdominal and type IV thoracoabdominal aortic aneurysms and summarizes the available evidence. The use of fenestrated SGs for complex aortic aneurysm disease has grown enormously the last years. SGs with fenestrations, scallops and occasionally branches have to be customized to each patient's anatomy and precisely deployed in vivo. Bridging covered stents between the main graft and the target vessels eventually exclude the aneurysm preserving blood flow to vital organs. Multiple device morphologies have been used incorporating the visceral arteries in various combinations. High technical success rates and satisfactory perioperative outcomes are described as well as mid- and long-term success and durability including target vessel and branch stent perfusion, data emerging mainly from high volume specialized centers. Percentage of target vessel successfully perfused was reported between 90.5 and 100%. 30-day mortality is reported between 0% and 4.1% while the lowest type 1 or type 3 endoleak rates were 2.5% and 1.3% respectively. Migration rates are kept below 3%. Renal failure was the most frequent complication reported. Advances in SG technology have reduced but not eliminated secondary interventions. Outcomes depend mostly on proximal extension of the disease which increases also the complexity of the repair. High level of expertise and organizational facilities are required for better mid- and long-term outcomes. Fenestrated EVAR (fEVAR) has been shown to be safe and effective in the short and mid-term follow-up. Remaining issues including secondary interventions and the need for follow-up are still within the range of those reported for EVAR. These, continue to plague fEVAR for complex abdominal or type IV thoracoabdominal aortic aneurysms. PMID- 26845539 TI - Comparison of Nonablative Fractional Erbium Laser 1,340 nm and Microneedling for the Treatment of Atrophic Acne Scars: A Randomized Clinical Trial. AB - BACKGROUND: The efficacy and safety of nonablative fractional laser for acne scars treatment has been described in several studies. Recently, microneedling treatment has been showing promising results with lower costs, quick healing time, and low risk of postinflammatory hyperpigmentation (PIH). OBJECTIVE: To compare the effectiveness and safety of nonablative fractional erbium laser 1,340 nm and microneedling for the treatment of facial atrophic acne scars. METHODS: Forty-six patients with atrophic facial acne scars were randomized to microneedling and laser groups, receiving 3 sessions performed monthly. Two blinded dermatologists applied the validated "Quantitative Global Grading System for Postacne Scarring" scale, before, 2 months, and 6 months after the treatment. Side effects were recorded at each follow-up visit and patient's satisfaction was evaluated. RESULTS: Both groups showed a significant improvement, and there was no statistically significant difference between results of both therapies (p = .264). The erythema after each session was longer in the laser group and 13.6% subjects experienced PIH. No PIH was observed in the microneedling group. CONCLUSION: This study shows that both nonablative fractional laser 1,340 nm and microneedling are comparable and effective in the treatment of atrophic acne scars. Microneedling is well tolerated, with fewer side effects and lower down time. PMID- 26845538 TI - Reassessing Melanonychia Striata in Phototypes IV, V, and VI Patients. AB - BACKGROUND: Racial melanonychia striata is a nail plate dyschromia described as a gray coloration of the background in dermatoscopy and hypermelanosis in histology. However, many cases with brown or black coloration of the background in the dermatoscopic examination have been followed. OBJECTIVE: Evaluate racial melanonychia striata dermatoscopical patterns and histological diagnosis in Fitzpatrick skin Types IV, V, or VI population. MATERIALS AND METHODS: 482 Fitzpatrick skin Types IV, V, or VI patients, between 19 and 72 years of age, were clinically evaluated and underwent nail plate dermatoscopic examination. Fifty-eight patients presenting melanonychia striata and dermatoscopic patterns with brown or black coloration of the background were submitted to a nail matrix biopsy. When occurring in more than 1 digit, biopsy was performed in the lesion with the darkest coloration presented in dermatoscopy. RESULTS: All skin Types IV, V, or VI patients who had melanonychia striata, with brown or black coloration of the background in the dermatoscopic examination, revealed histopathological analysis compatible with hypermelanosis. CONCLUSION: Racial melanonychia in skin Types IV, V, or VI patients, resulting from hypermelanosis, may present brown or black coloration of the background in the dermatoscopic examination. PMID- 26845540 TI - Creating and Editing Video to Accompany Manuscripts. AB - BACKGROUND: The use of video can enhance the learning experience by demonstrating procedural techniques that are difficult to relay in writing. Several peer reviewed journals allow publication of videos alongside articles to complement the written text. OBJECTIVE: The purpose of this article is to instruct the dermatologic surgeon on how to create and edit a video using a smartphone, to accompany a article. METHODS: The authors describe simple tips to optimize surgical videography. The video that accompanies this article further demonstrates the techniques described. RESULTS: Creating a surgical video requires little experience or equipment and can be completed in a modest amount of time. CONCLUSION: Making and editing a video to accompany a article can be accomplished by following the simple recommendations in this article. In addition, the increased use of video in dermatologic surgery education can enhance the learning opportunity. PMID- 26845541 TI - Carbon Dioxide Laser: A Therapeutic Approach for Multiple Vulvar Epidermoid Cysts. PMID- 26845542 TI - Use of an Injectable Diphenhydramine Solution as the Local Anesthetic for Mohs Surgery. PMID- 26845543 TI - Ribavirin use in pediatric patients with Crimean Congo Hemorrhagic Fever: is it really necessary? PMID- 26845544 TI - Integration of endothelial protease-activated receptor-1 inflammatory signaling by ubiquitin. AB - PURPOSE OF REVIEW: The maintenance and integrity of the endothelial barrier is essential for vascular homeostasis. Endothelial barrier dysfunction is mediated by various inflammatory factors, many of which act through G protein-coupled receptors including protease-activated receptors (PARs). PARs are expressed in multiple cell types in the vasculature and mediate cellular responses to thrombin, the key effector protease of the coagulation cascade. Thrombin activation of PAR1 induces endothelial barrier permeability through multiple pathways. Here, we discuss the mechanism by which thrombin activation of PAR1 promotes endothelial barrier breakdown and highlight recent advances that have provided new insight into molecular mechanisms that control endothelial barrier integrity. RECENT FINDINGS: Although the signal transduction pathways induced by thrombin activation of PAR1 in endothelial cells have been extensively studied, the key regulatory mechanisms remain poorly understood. Posttranslational modifications are integral to the regulation of PAR1 signaling and recent studies suggest a novel function for ubiquitination of PAR1 in regulation of endothelial barrier permeability. SUMMARY: An understanding of how endothelial barrier permeability is regulated by thrombin activation of PAR1 is important for the discovery of new drug targets that can be manipulated to control endothelial barrier permeability and prevent progression of vascular inflammation. PMID- 26845545 TI - Brain size is controlled by the mammalian target of rapamycin (mTOR) in mice. AB - The number of neurons in the brain is mostly determined by neural progenitor proliferation and neurogenesis during embryonic development. Increase in postnatal brain size is largely dependent on cellular volume changes. The mammalian target of rapamycin (mTOR) signaling has been associated with cell proliferation and size determination in a variety of cell types. The role of mTOR signaling in neural development has been increasingly pursued due to its association with neurodevelopmental disorders and cancers. Surprisingly, however, there has been lack of in vivo genetic evidence that defines mTOR functions in neural progenitors during progenitor self-renewal and subsequent brain formation. Here, we discuss our recent evidence that mTOR signaling is required for the establishment of normal brain size during development. Mice lacking mTOR show smaller brain and reduced numbers of neural progenitors and neurons. Additionally, mTOR interacts with the Wnt signaling pathway in the control of neural progenitors. Our study establishes the mTOR signal as a key regulator of an evolutionarily conserved cascade that is responsible for vertebrate brain size. PMID- 26845546 TI - The Impact of Integrated Community Case Management of Childhood Diseases Interventions to Prevent Malaria Fever in Children Less than Five Years Old in Bauchi State of Nigeria. AB - BACKGROUND: Malaria accounts for about 300,000 childhood deaths and 30% of under five year old mortality in Nigeria annually. We assessed the impact of intervention strategies that integrated Patent Medicines Vendors into community case management of childhood-diseases, improved access to artemisinin combination therapy (ACT) and distributed bed nets to households. We explored the influence of household socioeconomic characteristics on the impact of the interventions on fever in the under-five year olds in Bauchi State Nigeria. METHODS: A cross sectional case-controlled, interventional study, which sampled 3077 and 2737 under-5 year olds from 1,588 and 1601 households in pre- and post-intervention periods respectively, was conducted from 2013 to 2015. Difference-in-differences and logistic regression analyses were performed to estimate the impact attributable to the interventions: integrated community case management of childhood illness which introduced trained public and private sector health providers and the possession of nets on the prevalence of fever. RESULTS: Two week prevalence of fever among under-fives declined from 56.6% at pre intervention to 42.5% at post-intervention. Fever-prevention fraction attributable to nets was statistically significant (OR = 0.217, 95% CI: 0.08 0.33). Children in the intervention group had significantly fewer incidence of fever than children in the control group had (OR = 0.765, 95% CI: 0.67-0.87). Although being in the intervention group significantly provided 23.5% protection against fever (95% CI: 0.13-0.33), the post-intervention likelihood of fever was also significantly less than at pre-intervention (OR = 0.57, 95% CI: 0.50-0.65). The intervention protection fraction against fever was statistically significant at 43.4% (OR = 0.434, 95% CI: 0.36-0.50). Logistic regression showed that the odds of fever were lower in households with nets (OR = 0.72, 95% CI: 0.60-0.88), among children whose mothers had higher education, in the post-intervention period (OR = 0.39, 95% CI: 0.33-0.46) and in the intervention group (OR = 0.52, 95% CI: 0.48-0.66). The odds of fever increased with higher socio-economic status of households (17.9%-19.5%). Difference-in-differences showed that the interventions significantly reduced occurrence of fever in the intervention group (OR = 1.70, 95% CI: 1.36-2.14). CONCLUSION: The interventions were effective in reducing the prevalence and the likelihood of childhood malaria fever. Taken to scale, these can significantly reduce the burden of malaria fever in the under five year old children. PMID- 26845547 TI - Identification of Male- and Female-Specific Olfaction Genes in Antennae of the Oriental Fruit Fly (Bactrocera dorsalis). AB - The oriental fruit fly (Bactrocera dorsalis) is a species of tephritid fruit fly, endemic to Southeast Asia but also introduced to many regions of the US, and it is one of the major pest species with a broad host range of cultivated and wild fruits. Although males of B. dorsalis respond strongly to methyl eugenol and this is used for monitoring and estimating populations, the molecular mechanism of the oriental fruit fly olfaction has not been elucidated yet. Therefore, in this project, using next generation sequencing technologies, we sequenced the transcriptome of the antennae of male and female adults of B. dorsalis. We identified a total of 20 candidate odorant binding proteins (OBPs), 5 candidate chemosensory proteins (CSPs), 35 candidate odorant receptors (ORs), 12 candidate ionotropic receptors (IRs) and 4 candidate sensory neuron membrane proteins (SNMPs). The sex-specific expression of these genes was determined and a subset of 9 OR genes was further characterized by qPCR with male and female antenna, head, thorax, abdomen, leg and wing samples. In the male antennae, 595 genes showed a higher expression, while 128 genes demonstrated a higher expression in the female antennae. Interestingly, 2 ORs (BdorOR13 and BdorOR14) were highly and specifically expressed in the antennae of males, and 4 ORs (BdorOR13, BdorOR16, BdorOR18 and BdorOR35) clustered with DmOR677, suggesting pheromone reception. We believe this study with these antennae-enriched OBPs, CSPs, ORs, IRs and SNMPs can play an important role in the detection of pheromones and general odorants, and so in turn our data improve our current understanding of insect olfaction at the molecular level and provide important information for disrupting the behavior of the oriental fruit fly using chemical communication methods. PMID- 26845549 TI - Omega-3 Fatty Acids in the Management of Epilepsy. AB - Omega-3 and omega-6 fatty acids are polyunsaturated fatty acids (PUFAs) with multiple double bonds. Linolenic and alpha-linolenic acids are omega-6 and omega 3 PUFAs, precursors for the synthesis of long-chain PUFAs (LC-PUFAs), such as arachidonic acid (omega-6 PUFA), and eicosapentaenoic and docosahexaenoic acids (omega-3 PUFAs). The three most important omega-3 fatty acids are alpha linolenic, eicosapentaenoic and docosahexaenoic acids, which cannot be synthesized in enough amounts by the body, and therefore they must be supplied by the diet. Omega-3 fatty acids are essential for the correct functioning of the organism and participate in many physiological processes in the brain. Epilepsy is a common and heterogeneous chronic brain disorder characterized by recurrent epileptic seizures leading to neuropsychiatric disabilities. The prevalence of epilepsy is high achieving about 1% of the general population. There is evidence suggesting that omega-3 fatty acids may have neuroprotective and anticonvulsant effects and, accordingly, may have a potential use in the treatment of epilepsy. In the present review, the potential use of omega-3 fatty acids in the treatment of epilepsy, and the possible proposed mechanisms of action are discussed. The present article summarizes the recent knowledge of the potential protective role of dietary omega-3 fatty acids in epilepsy. PMID- 26845550 TI - Aporphines and Parkinson's Disease: Medical Tools for the Future. AB - Parkinson's disease is a motor dysfunction that has been widely studied but many of the reports on commercial drugs for the treatment of this disease have afforded some undesirable side effects that generate an extensive and unviable treatment by economic costs and due to the bioavailability of the assayed compounds. At present, some molecules are used as L-DOPA agonists or can change the dopamine concentrations in the CNS. Thus, the use of aporphine-type alkaloids has given a real alternative due to the diverse natural sources where can be isolated or to obtain them by means of conventional syntheses. Isoquinoline alkaloids as liriodenine, phenanthrene-type alkaloids, alkoxy-hydroxyaporphine, aminothiazole-aporphine or lipoic ester aporphine derivatives are some of the examples to be considered in this mini-review, wherein the applied pharmacological effects to reduce the motor disorders and the possible medical properties of these alkaloids on the dopaminergic receptors are analyzed. PMID- 26845548 TI - Repeat-Associated Fission Yeast-Like Regional Centromeres in the Ascomycetous Budding Yeast Candida tropicalis. AB - The centromere, on which kinetochore proteins assemble, ensures precise chromosome segregation. Centromeres are largely specified by the histone H3 variant CENP-A (also known as Cse4 in yeasts). Structurally, centromere DNA sequences are highly diverse in nature. However, the evolutionary consequence of these structural diversities on de novo CENP-A chromatin formation remains elusive. Here, we report the identification of centromeres, as the binding sites of four evolutionarily conserved kinetochore proteins, in the human pathogenic budding yeast Candida tropicalis. Each of the seven centromeres comprises a 2 to 5 kb non-repetitive mid core flanked by 2 to 5 kb inverted repeats. The repeat associated centromeres of C. tropicalis all share a high degree of sequence conservation with each other and are strikingly diverged from the unique and mostly non-repetitive centromeres of related Candida species--Candida albicans, Candida dubliniensis, and Candida lusitaniae. Using a plasmid-based assay, we further demonstrate that pericentric inverted repeats and the underlying DNA sequence provide a structural determinant in CENP-A recruitment in C. tropicalis, as opposed to epigenetically regulated CENP-A loading at centromeres in C. albicans. Thus, the centromere structure and its influence on de novo CENP-A recruitment has been significantly rewired in closely related Candida species. Strikingly, the centromere structural properties along with role of pericentric repeats in de novo CENP-A loading in C. tropicalis are more reminiscent to those of the distantly related fission yeast Schizosaccharomyces pombe. Taken together, we demonstrate, for the first time, fission yeast-like repeat-associated centromeres in an ascomycetous budding yeast. PMID- 26845551 TI - Neuroprotective Role of Natural Polyphenols. AB - Neurodegenerative diseases cause a progressive functional alteration of neuronal systems, resulting in a state of dementia which is considered one of the most common psychiatric disorders of the elderly. Dementia implies an irreversible impairment of intellect that increases with age causing alteration of memory, language and behavioral problems. The most common form, which occurs in more than half of all cases, is Alzheimer's disease, characterized by accumulation of amyloid plaques and neurofibrillary tangles. Neuroinflammation and oxidative stresses have been considered as a hallmark of Alzheimer disease, playing a crucial role in neurotoxicity. For this reason, an adequate antioxidant strategy may improve the treatment of neurodegenerative diseases and dementia. Several studies support the neuroprotective abilities of polyphenolic compounds resulting in neuronal protection against injury induced by neurotoxins, ability to suppress neuroinflammation and the potential to promote memory, learning and cognitive functions. We critically reviewed here the therapeutic potential of pure herbal compounds (e.g., green tea polyphenol (-)- epigallocatechin-3-gallate, resveratrol, curcumin, quercetin and others) and extracts enriched in polyphenols showing the most promising neuroprotective effects. We are also presenting data on the ability of an extract derived from elderberry, Sambucus nigra, possessing elevated polyphenolic content and antioxidant capacity to protect neuronal cells against oxidizing agents. PMID- 26845552 TI - Cannabinoids for the Treatment of Schizophrenia: An Overview. AB - Cannabinoids are found to be very useful in psychiatry because of their antipsychotic properties suggesting a therapeutic use as neuroleptic agents in limiting psychotic diseases. Cannabinoids treatments are both able to reduce the typical symptoms of schizophrenia and to slow down the disease aggravation. In the present review, we reported recent studies supporting the idea that the cannabinoid system may modulate the activity of the striatum and temporal cortex linked to psychosis and schizophrenia. Furthermore, anatomical, electrophysiological, pharmacological and biochemical data suggest that the psychotic disorders related to the impaired cannabinoid system may lead to the development of novel compounds that selectively target specific elements of the cannabinoid system. PMID- 26845553 TI - Designing Multi-Targeted Therapeutics for the Treatment of Alzheimer's Disease. AB - Due to multi-faceted pathology of AD; no drug can seize the progress of the disease, whereas only the symptomatic treatment is available at the moment. Several drug classes to treat AD are available in clinical use, AChEIs being the most prescribed. In addition to AChEIs, secretase enzymes and iron chelators have turned out to be the focus of research and the popular targets in drug discovery against AD. The latest approaches such as immunotherapy, multi-targeted drug ligand design, AChE inhibitors, antioxidants, metal chelators, monoamine oxidase (MAO) inhibitors, antiinflammatory drugs, and N-methyl-D-aspartate (NMDA) inhibitors are currently in use to cure this disease to some extent. But, there is a certain need to develop new drugs to fight with AD, particularly acting on multi-targets or with dual mechanisms of action. In this review, a particular emphasis will be focused on multitargets aiming at AD to design new drug molecules with respect to treatment strategies and preventive measures. Since the underlying pathogenesis of AD is complicated and still under investigation, the attempts to design highly selective and potent agents to treat AD are quite intensively continuing. In this respect, designing novel drugs with dual/multi acting mechanisms seems to be more rational. PMID- 26845554 TI - Neuroprotective Effects of Fisetin in Alzheimer's and Parkinson's Diseases: From Chemistry to Medicine. AB - According to the epidemiological reports published by the World Health Organization, the proportion of elderly people (over 60 years) will increase from 11% to 22% by 2050 worldwide. This increase will be associated with a growing rate of morbidity and mortality of age-related diseases. Mental and neurodegenerative diseases are important health problems in elderly people. Therefore, recent research has been focused on finding effective neuroprotective agents with low adverse effects. Over the last two decades, much attention has been drawn to plant-derived bioactive compounds as novel therapeutic agents for treatment of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Among them, flavonoid chemical class is known as one of the most bioactive and non-toxic phytochemicals, which are widely found in different herbal medicines and edible plants. Fisetin is one of the most common and bioactive flavonoids which possesses potential neuroprotective effects. Fisetin also enhances learning and memory, decreases neuronal cell death, and suppresses oxidative stress. The present paper aims to critically evaluate the available literature regarding the beneficial effects of fisetin on neurodegenerative diseases, especially AD and PD. In addition, we provide information regarding the chemistry, sources, bioavailability and clinical impacts of fisetin to provide a broad spectrum for the use of this compound as a new approach to the treatment of AD and PD. PMID- 26845555 TI - Resveratrol as a Potential Therapeutic Candidate for the Treatment and Management of Alzheimer's Disease. AB - Resveratrol (3,4',5-trihydroxystilbene) is a naturally occurring phytochemical present in red wine, grapes, berries, chocolate and peanuts. Clinically, resveratrol has exhibited significant antioxidant, anti-inflammatory, anti-viral, and anti-cancer properties. Although resveratrol was first isolated in 1940, it was not until the last decade that it was recognised for its potential therapeutic role in reducing the risk of neurodegeneration, and Alzheimer's disease (AD) in particular. AD is the primary cause of progressive dementia. Resveratrol has demonstrated neuroprotective effects in several in vitro and in vivo models of AD. Apart from its potent antioxidant and anti-inflammatory roles, evidence suggests that resveratrol also facilitates non-amyloidogenic breakdown of the amyloid precursor protein (APP), and promotes removal of neurotoxic amyloid beta (Abeta) peptides, a critical step in preventing and slowing down AD pathology. Resveratrol also reduces damage to neuronal cells via a variety of additional mechanisms, most notably is the activation of NAD(+)-dependent histone deacetylases enzymes, termed sirtuins. However in spite of the considerable advances in clarifying the mechanism of action of resveratrol, it is unlikely to be effective as monotherapy in AD due to its poor bioavailability, biotransformation, and requisite synergism with other dietary factors. This review summarizes the relevance of resveratrol in the pathophysiology of AD. It also highlights why resveratrol alone may not be an effective single therapy, and how resveratrol coupled to other compounds might yet prove an effective therapy with multiple targets. PMID- 26845556 TI - A Systematic Review of Plant-Derived Natural Compounds for Anxiety Disorders. AB - Anxiety disorders are the most common mental illnesses affecting human beings. They range from panic to generalized anxiety disorders upsetting the well-being and psychosocial performance of patients. Several conventional anxiolytic drugs are being used which in turn results in several adverse effects. Therefore, studies to find suitable safe medicines from natural sources are being conducted by researchers. The aim of the present study is to comprehensively review phytochemical compounds with well-established anxiolytic activities and their structure-activity relationships as well as neuropsychopharmacological aspects. Results showed that phytochemicals like; alkaloids, flavonoids, phenolic acids, lignans, cinnamates, terpenes and saponins possess anxiolytic effects in a wide range of animal models of anxiety. The involved mechanisms include interaction with gamma-aminobutyric acid (GABA)A receptors at benzodiazepine (BZD) and non BZD sites with various affinity to different subunits, serotonergic 5 hydrodytryptamine (5-HT)1A and 5-HT2A/C receptors, noradrenergic and dopaminergic systems, glycine and glutamate receptors, and kappa-opioid receptor as well as cannabinoid (CB)1 and CB2 receptors. Phytochemicals also modulate the hypothalamo pituitary-adrenal (HPA) axis, the levels of pro-inflammatory cytokines like interleukin (IL)-2, IL-6, IL-1beta and tumor necrosis factor (TNF)-alpha, and improve brain derived neurotrophic factor (BDNF) levels. Transient receptor potential cation channel subfamily V (TRPV)3, nitric oxide cyclic guanosine monophosphate (NOcGMP) pathway and monoamine oxidase enzymes are other targets of phytochemicals with anxiolytic activity. Taking together, these phytochemicals may be considered as supplements to conventional anxiolytic therapies in order to improve efficacy and reduce adverse effects. Further preclinical and clinical studies are still needed in order to recognize the structure-activity relationships, metabolism, absorption, and neuropsychopharmacological mechanisms of plantderived natural agents. PMID- 26845557 TI - Differentiation of Aedes aegypti and Aedes notoscriptus (Diptera: Culicidae) eggs using scanning electron microscopy. AB - Aedes notoscriptus and Aedes aegypti are both peri-domestic, invasive container breeding mosquitoes. While the two potential arboviral vectors are bionomically similar, their sympatric distribution in Australia is limited. In this study, analyses of Ae. aegypti and Ae. notoscriptus eggs were enabled using scanning electron microscopy. Significant variations in egg length to width ratio and outer chorionic cell field morphology between Ae. aegypti and Ae. notoscriptus enabled distinction of the two species. Intraspecific variations in cell field morphology also enabled differentiation of the separate populations of both species, highlighting regional and global variation. Our study provides a comprehensive comparative analysis of inter- and intraspecific egg morphological and morphometric variation between two invasive container-breeding mosquitoes. The results indicate a high degree of intraspecific variation in Ae. notoscriptus egg morphology when compared to the eggs of Ae. aegypti. Comparative morphological analyses of Ae. aegypti and Ae. notoscriptus egg attributes using SEM allows differentiation of the species and may be helpful in understanding egg biology in relation to biotope of origin. PMID- 26845559 TI - Understanding the Role of Poloxamer 407 based Thermoreversible In Situ Gelling Hydrogel for Delivery of PEGylated Melphalan Conjugate. AB - BACKGROUND: Hydrogels are the polymeric network, which can retain large amount of water. Thus, these delivery systems always remained an issue of intensive research among the scientist fraternity. OBJECTIVE: In this piece of work, we have reconnoitered the significance of the PEGylated anticancer loaded drug onto poloxamer based thermoresponsive injectable hydrogel to understand the role of delivery system. METHOD: To accomplish the objective, firstly it was necessary to improve the solubility of the melphalan, achieved by PEGylation of the drug with two grades of linear methoxy poly ethylene glycol (M-PEG), viz. M-PEG 2000 and 5000 Da to form a PEGylated melphalan conjugate (MLPEG). In our previous study, we have found that the prepared conjugates were efficiently enhanced the solubility of the melphalan and significantly reduced the hemolytic effect due to the presence of the PEG chains. Thus, in the present work, the prepared conjugates (MLPEG 5000 and 2000) were loaded to the thermosensitive Poloxamer 407 (P407) gel to produce an injectable hydrogel (MPX). To underline the reduction of the initial burst of the drug at the site of action, one of the hydrogels was prepared in the presence of the NaCl salt. RESULTS: This in turn, tightened the PEO chains and remarkably reduced the drug's initial burst from the delivery system as only 43 % of drug was released during 2 hours from MPX-CG hydrogel. Moreover, a lower diffusion coefficient (D) was noticed for MPX-CG gel as compared with MPX-7.4 gel. To confirm the depot formation, prepared hydrogels were administered to Wistar rats via subcutaneous and intramuscular routes. CONCLUSION: Thus, P407 based injectable hydrogel could play an important role for the delivery of a low dose-alkylating agent with reduced host cytotoxicity. PMID- 26845558 TI - Ensemble Tractography. AB - Tractography uses diffusion MRI to estimate the trajectory and cortical projection zones of white matter fascicles in the living human brain. There are many different tractography algorithms and each requires the user to set several parameters, such as curvature threshold. Choosing a single algorithm with specific parameters poses two challenges. First, different algorithms and parameter values produce different results. Second, the optimal choice of algorithm and parameter value may differ between different white matter regions or different fascicles, subjects, and acquisition parameters. We propose using ensemble methods to reduce algorithm and parameter dependencies. To do so we separate the processes of fascicle generation and evaluation. Specifically, we analyze the value of creating optimized connectomes by systematically combining candidate streamlines from an ensemble of algorithms (deterministic and probabilistic) and systematically varying parameters (curvature and stopping criterion). The ensemble approach leads to optimized connectomes that provide better cross-validated prediction error of the diffusion MRI data than optimized connectomes generated using a single-algorithm or parameter set. Furthermore, the ensemble approach produces connectomes that contain both short- and long-range fascicles, whereas single-parameter connectomes are biased towards one or the other. In summary, a systematic ensemble tractography approach can produce connectomes that are superior to standard single parameter estimates both for predicting the diffusion measurements and estimating white matter fascicles. PMID- 26845560 TI - A New Glabrous Gene (csgl3) Identified in Trichome Development in Cucumber (Cucumis sativus L.). AB - Spines or trichomes on the fruit of cucumbers enhance their commercial value in China. In addition, glabrous mutants exhibit resistance to aphids and therefore their use by growers can reduce pesticide residues. Previous studies have reported two glabrous mutant plants containing the genes, csgl1 and csgl2. In the present study, a new glabrous mutant, NCG157, was identified showing a gene interaction effect with csgl1 and csgl2. This mutant showed the glabrous character on stems, leaves, tendrils, receptacles and ovaries, and there were no spines or tumors on the fruit surface. Inheritance analysis showed that a single recessive gene, named csgl3, determined the glabrous trait. An F2 population derived from the cross of two inbred lines 9930 (a fresh market type from Northern China that exhibits trichomes) and NCG157 (an American processing type with glabrous surfaces) was used for genetic mapping of the csgl3 gene. By combining bulked segregant analysis (BAS) with molecular markers, 18 markers, including two simple sequence repeats (SSR), nine insertion deletions (InDel) and seven derived cleaved amplified polymorphism sequences (dCAPs), were identified to link to the csgl3 gene. All of the linked markers were used as anchor loci to locate the csgl3 gene on cucumber chromosome 6. The csgl3 gene was mapped between the dCAPs markers dCAPs-21 and dCAPs-19, at genetic distances of 0.05 cM and 0.15 cM, respectively. The physical distance of this region was 19.6 kb. Three markers, InDel-19, dCAPs-2 and dCAPs-11, co-segregated with csgl3. There were two candidate genes in the region, Csa6M514860 and Csa6M514870. Quantitative real time PCR showed that the expression of Csa6M514870 was higher in the tissues of 9930 than that of NCG157, and this was consistent with their phenotypic characters. Csa6M514870 is therefore postulated to be the candidate gene for the development of trichomes in cucumber. This study will facilitate marker-assisted selection (MAS) of the smooth plant trait in cucumber breeding and provide for future cloning of csgl3. PMID- 26845561 TI - Numerical distance effect in patients with schizophrenia. AB - There is growing evidence showing that mental representation of numbers is impaired in patients with schizophrenia. Yet, no study has examined the distance effect in the patients. We assessed the distance effect using two number size comparison tasks, with different number references (5 and 7) in 23 patients and 28 healthy individuals. Response times and error rates significantly increased when the distances between the centered references and the targets decreased in both groups. However, patients responded significantly slower and had more error rates compared to controls. Our finding indicates distance effect in patients is similar to the controls, indicating an automatic numerical processing is preserved in patients with schizophrenia. PMID- 26845562 TI - Developmental expression of Kv1 voltage-gated potassium channels in the avian hypothalamus. AB - Specialized hypothalamic neurons integrate the homeostatic balance between food intake and energy expenditure, processes that may become dysregulated during the development of diabetes, obesity, and other metabolic disorders. Shaker family voltage-gated potassium channels (Kv1) contribute to the maintenance of resting membrane potential, action potential characteristics, and neurotransmitter release in many populations of neurons, although hypothalamic Kv1 channel expression has been largely unexplored. Whole-cell patch clamp recordings from avian hypothalamic brain slices demonstrate a developmental shift in the electrophysiological properties of avian arcuate nucleus neurons, identifying an increase in outward ionic current that corresponds with action potential maturation. Additionally, RT-PCR experiments identified the early expression of Kv1.2, Kv1.3, and Kv1.5 mRNA in the embryonic avian hypothalamus, suggesting that these channels may underlie the electrophysiological changes observed in these neurons. Real-time quantitative PCR analysis on intact microdissections of embryonic hypothalamic tissue revealed a concomitant increase in Kv1.2 and Kv1.5 gene expression at key electrophysiological time points during development. This study is the first to demonstrate hypothalamic mRNA expression of Kv1 channels in developing avian embryos and may suggest a role for voltage-gated ion channel regulation in the physiological patterning of embryonic hypothalamic circuits governing energy homeostasis. PMID- 26845563 TI - The impact of childhood maltreatment on redox state: Relationship with oxidative damage and antioxidant defenses in adolescents with no psychiatric disorder. AB - Early life stress (ELS) has been associated with biological and psychosocial alterations due to developmental reprogramming. Here, we investigated whether childhood maltreatment is associated with an imbalance between the production of oxidative markers and antioxidant defenses. Thirty adolescents with no psychiatric disorder but reporting childhood maltreatment and twenty-seven adolescents with no psychiatric disorder and no history of ELS were recruited for the study. Childhood maltreatment was investigated by the Childhood Trauma Questionnaire (CTQ). Redox state was estimated by plasma levels of protein carbonylation, total thiol content (SH), superoxide dismutase (SOD), glutathione peroxidase (GPx), as well as total reactive antioxidant potential (TRAP). Childhood maltreatment was associated with oxidative stress as shown by increased protein carbonylation. Interestingly, adolescents exposed to maltreatment also displayed higher SOD levels, TRAP kinetics and reduced GPx levels when compared with adolescents who had not undergone childhood maltreatment. No significant differences were observed for SH levels. Taken together, we provide novel evidence indicating that childhood maltreatment is associated with increased oxidative stress markers in otherwise healthy adolescents. PMID- 26845564 TI - The ubiquitination of serotonin transporter in lymphoblasts derived from fluvoxamine-resistant depression patients. AB - There is insufficient serotonergic neuronal function in the pathophysiology of major depressive disorder (MDD). Serotonin transporter (SERT) plays a critical role in terminating the function of serotoninergic neurons. SERT is linked to vulnerability to MDD and is an important target for antidepressants. The expression of SERT in lymphocytes and platelets is associated with their expression in central nervous system. Most of the clinical studies that have analyzed the role of SERT in depression have focused on absolute expression of SERT in the brain or peripheral tissue. Our study has shown that the SERT protein is ubiquitinated, which has been implicated through the SERT stability and depressive behaviors in mice. In our study, we have used lymphoblasts derived from the peripheral blood lymphocytes to quantitatively examine SERT protein expression and ubiquitination in fluvoxamine-responsive and fluvoxamine-resistant MDD patients. We found that the protein levels of SERT were higher in the fluvoxamine-resistant MDD patients. Ubiquitinated protein levels of SERT were lower in the fluvoxamine-resistant MDD patients. The proteasome inhibitor failed to increase the protein levels of SERT in both fluvoxamine-responsive and fluvoxamine-resistant MDD patients. In sum, these findings suggest that the downregulation of the ubiquitination of SERT protein induces insufficient degradation of SERT by proteasome, which resulted in the upregulation of SERT protein in fluvoxamine-resistant MDD patients. Although further studies with various populations will be required to generalize results, SERT protein expression, ubiquitination, and the responsiveness of SERT expression to proteasome inhibitor are potential biomarkers for the diagnosis of MDD and antidepressant efficacy. PMID- 26845566 TI - The Circulating Treg/Th17 Cell Ratio Is Correlated with Relapse and Treatment Response in Pulmonary Sarcoidosis Patients after Corticosteroid Withdrawal. AB - OBJECTIVES: Pulmonary sarcoidosis is an immune-mediated disease, and some patients can be effectively treated with corticosteroids. However, nearly half of all sarcoidosis patients relapse after corticosteroid withdrawal. Different subsets of CD4+ helper T cells participate in the immunopathogenesis of sarcoidosis. Thus, the aims of our study were to investigate whether the circulating subsets of CD4+ helper T cells were associated with sarcoidosis relapse and with its remission after retreatment. Additionally, we identified a useful biomarker for predicting the relapse and remission of sarcoidosis patients. METHODS: Forty-two patients were enrolled in the present study who had previously been diagnosed with pulmonary sarcoidosis and treated with corticosteroids. The patients were allocated into either a stable group if they exhibited sustained remission (n = 22) or a relapse group if they experienced clinical or radiological recurrence after treatment withdrawal (n = 20). Peripheral blood cells were collected from these patients and analyzed to determine the frequencies of subsets of circulating CD4+ helper T cells by flow cytometry. The patients in the relapse group were retreated with corticosteroids and immunosuppressive agents and were then reevaluated to determine the frequencies of dynamic subsets of circulating CD4+ helper T cells after remission. RESULTS: The frequencies of circulating Tregs were significantly increased concomitant with a decrease in the circulating Th17 cell frequency in the relapsed patients compared with the stable patients. The Treg/Th17 ratio was negatively correlated with sarcoidosis activity and was sensitive to retreatment. In addition, the percentage of isolated CD45RO+Ki67+ Tregs was higher in the patients who were stable and in those who recovered after retreatment than in those who relapsed. CONCLUSIONS: An imbalance between Tregs and Th17 cells is associated with pulmonary sarcoidosis relapse after corticosteroid withdrawal. The circulating Treg/Th17 ratio could serve as an alternative marker for monitoring pulmonary sarcoidosis relapse after the end of corticosteroid treatment and for rapidly predicting the response to retreatment. PMID- 26845568 TI - Structural remodeling during amyloidogenesis of physiological Nalpha-acetylated alpha-synuclein. AB - The misfolding and aggregation of the presynaptic protein alpha-synuclein (AS) into amyloid fibrils is pathognomonic of Parkinson's disease, though the mechanism by which this structural conversion occurs is largely unknown. Soluble oligomeric species that accumulate as intermediates in the process of fibril formation are thought to be highly cytotoxic. Recent studies indicate that oligomer-to-fibril AS transition plays a key role in cell toxicity and progression of neurodegeneration. We previously demonstrated that a subgroup of oligomeric AS species are ordered assemblies possessing a well-defined pattern of intermolecular contacts which are arranged into a distinctive antiparallel beta sheet structure, as opposed to the parallel fibrillar fold. Recently, it was demonstrated that the physiological form of AS is N-terminally acetylated (Ac AS). Here, we first showed that well-characterized conformational ensembles of Ac AS, namely monomers, oligomers and fibrils, recapitulate many biophysical features of the nonacetylated protein, such as hydrodynamic, tinctorial, structural and membrane-leakage properties. Then, we relied on ATR-FTIR spectroscopy to explore the structural reorganization during Ac-AS fibrillogenesis. We found that antiparallel beta-sheet transient intermediates are built-up at early stages of aggregation, which then evolve to parallel beta sheet fibrils through helix-rich/disordered species. The results are discussed in terms of regions of the protein that might participate in this structural rearrangement. Our work provides new insights into the complex conformational reorganization occurring during Ac-AS amyloid formation. PMID- 26845567 TI - Effect of Erythropoietin, Iron Deficiency and Iron Overload on Liver Matriptase-2 (TMPRSS6) Protein Content in Mice and Rats. AB - Matriptase-2 (TMPRSS6) is an important negative regulator of hepcidin expression; however, the effects of iron overload or accelerated erythropoiesis on liver TMPRSS6 protein content in vivo are largely unknown. We determined TMPRSS6 protein content in plasma membrane-enriched fractions of liver homogenates by immunoblotting, using a commercial antibody raised against the catalytic domain of TMPRSS6. Plasma membrane-enriched fractions were obtained by centrifugation at 3000 g and washing. TMPRSS6 was detected in the 3000 g fraction as a 120 kDa full length protein in both mice and rats. Feeding of iron-deficient diet as well as erythropoietin treatment increased TMPRSS6 protein content in rats and mice by a posttranscriptional mechanism; the increase in TMPRSS6 protein by erythropoietin was also observed in Bmp6-mutant mice. Administration of high doses of iron to mice (200, 350 and 700 mg/kg) decreased TMPRSS6 protein content. Hemojuvelin was detected in the plasma membrane-enriched fractions of control animals as a full length protein of approximately 52 kDa; in iron deficient animals, the full length protein was partially cleaved at the N-terminus, resulting in an additional weak band of approximately 47 kDa. In livers from hemojuvelin-mutant mice, TMPRSS6 protein content was strongly decreased, suggesting that intact hemojuvelin is necessary for stable TMPRSS6 expression in the membrane. Overall, the results demonstrate posttranscriptional regulation of liver TMPRSS6 protein by iron status and erythropoietin administration, and provide support for the interaction of TMPRSS6 and hemojuvelin proteins in vivo. PMID- 26845565 TI - BS69/ZMYND11 C-Terminal Domains Bind and Inhibit EBNA2. AB - Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) plays an important role in driving immortalization of EBV-infected B cells through regulating the expression of many viral and cellular genes. We report a structural study of the tumor suppressor BS69/ZMYND11 C-terminal region, comprised of tandem coiled-coil-MYND domains (BS69CC-MYND), in complex with an EBNA2 peptide containing a PXLXP motif. The coiled-coil domain of BS69 self-associates to bring two separate MYND domains in close proximity, thereby enhancing the BS69 MYND-EBNA2 interaction. ITC analysis of BS69CC-MYND with a C-terminal fragment of EBNA2 further suggests that the BS69CC-MYND homodimer synergistically binds to the two EBNA2 PXLXP motifs that are respectively located in the conserved regions CR7 and CR8. Furthermore, we showed that EBNA2 interacts with BS69 and down-regulates its expression at both mRNA and protein levels in EBV-infected B cells. Ectopic BS69CC-MYND is recruited to viral target promoters through interactions with EBNA2, inhibits EBNA2-mediated transcription activation, and impairs proliferation of lymphoblastoid cell lines (LCLs). Substitution of critical residues in the MYND domain impairs the BS69-EBNA2 interaction and abolishes the BS69 inhibition of the EBNA2-mediated transactivation and LCL proliferation. This study identifies the BS69 C-terminal domains as an inhibitor of EBNA2, which may have important implications in development of novel therapeutic strategies against EBV infection. PMID- 26845569 TI - Ferrous iron and alpha-ketoglutarate-dependent dioxygenases in the biosynthesis of microbial natural products. AB - Apart from its vital role as the terminal electron acceptor in oxidative phosphorylation in nature, dioxygen also serves as a universal agent which diversifies natural products by oxidative transformations. Ferrous iron and alpha ketoglutarate (alphaKG)-dependent dioxygenases (alphaKGDs) are versatile enzymes that use dioxygen as an oxidant to catalyse various reactions via CH bond activation, including hydroxylation, dealkylation, desaturation, epoxidation, epimerisation, halogenation, cyclisation, peroxide formation, and ring expansion/contraction reactions. This review updates the reported alphaKGDs that catalyse reactions related to microbial natural product biosynthesis in the past 10 years. We hope that the versatility of alphaKGDs shown here can serve as an inspiration for future engineering and catalyst design, which could provide alternative methods to meet the on-going demand for fine chemicals and pharmaceutics. PMID- 26845571 TI - Intraductal pneumatic lithotripsy for salivary stones with the StoneBreaker: Preliminary experience. AB - OBJECTIVES/HYPOTHESIS: To test the effectiveness of a newly approved pneumatic lithotripter for fragmentation of salivary stones. STUDY DESIGN: Retrospective study in a tertiary referral center. METHODS: In 44 patients, 49 stones were primarily treated with direct endoscopic guidance using the StoneBreaker. Twenty three stones were located in the parotid gland and 26 in the submandibular gland. RESULTS: Complete fragmentation was achieved combined extracorporeal in 97.7% of the stones. All of the patients became symptom free, and 97.7% were stone free. Three patients underwent lithotripsy procedures. Altogether additional treatment was necessary in five cases to achieve stone clearance. The reason for residual sialolithiasis was intraparenchymal repulsion of a residual fragment (n = 1). The glands were preserved in all cases. CONCLUSIONS: Endoscopically guided intraductal pneumatic lithotripsy using the StoneBreaker is an effective and promising procedure for the treatment of sialolithiasis. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:1545-1550, 2016. PMID- 26845572 TI - The Effect of Hippocampal Cognitive Impairment and XIAP on Glucose and Lipids Metabolism in Rats. AB - BACKGROUND/AIMS: To investigate the effect of cognitive impairment and X-linked inhibitor of apoptosis protein (XIAP) on glucolipid metabolism. MATERIALS AND METHODS: beta-amyloid (Abeta 1-42) was injected into the hippocampus of rats to establish a cognitive impairment model. Trans-activator of transcription (TAT) XIAP fusion protein (the TAT-XIAP group), PBS (the model group), or XIAP antisense oligonucleotides (the ASODN group) was injected into the lateral ventricles of the rats to increase and decrease the activity of XIAP in the hippocampus. To determine the level of blood glucose and lipids, adenosine monophosphate-activated protein kinase (AMPK) expression of liver and hipppocamual neuronal apoptosis. RESULTS: The levels of FPG, TG, TC and LDL were significantly higher in the TAT-XIAP group, the model group and the ASODN group than in the blank group (P < 0.05); however, the HDL level showed no significant change in all groups of rats. The apoptosis indexes of the rat hippocampal CA1 neuron were 68.44 +/- 4.31%, 13.21 +/- 2.30%, 56.68 +/- 4.771%, and 87.51 +/- 6.63% in the model group, the blank group, the TAT-XIAP group and the ASODN group, respectively. Gastrointestinal motility was less frequent (per time unit) in the model group, the ASODN group and the TAT-XIAP group than in the blank group. Compared with the model group, gastrointestinal motility was significantly less frequent in the ASODN group and was significantly more frequent in the TAT XIAP group. Compared with the blank group, the model group had a significantly lower gastric emptying rate and intestinal propulsive rate. Compared with the model group, the gastric emptying rate and intestinal propulsive rate were significantly lower in the ASODN group and were significantly higher in the TAT XIAP group. Compared with the blank group, the expressions of AMPK mRNA, and AMPK protein were significantly reduced in the model group, the TAT-XIAP group, and the ASODN group. AMPK expression was significantly increased in the TAT-XIAP group and was significantly decreased in the ASODN group than in the model group. CONCLUSION: Cognitive impairment and hippocampal neuron apoptosis can cause glucose and lipids metabolic abnormalities, possibly by regulating gastrointestinal motility and AMPK expression in the liver. The changes in the function of XIAP, which is an anti-apoptotic protein in the hippocampus, may affect the metabolism of glucose and lipids. PMID- 26845573 TI - Systematic reviews in oral health: a quality imperative. AB - Systematic reviews must be conducted responsibly, eliminating any scope for error and bias. The reporting quality of a systematic review should follow and conform to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta Analyses) guidelines. AMSTAR (Assessment of Multiple Systematic Reviews) is an assessment tool, which has been developed specifically to assess the quality of the process used in conducting the review. There has been a significant increase in the number of systematic reviews in oral health and several reports have been published stating low AMSTAR ratings of systematic reviews in dentistry. Systematic reviews answer key clinical questions objectively, and are often used to underpin clinical guidelines in oral health. If the quality of these reviews is compromised, this can result in inadequate or inappropriate clinical guidelines. Consequently, ensuring consistent high quality is a key imperative for systematic reviews in oral health. PMID- 26845574 TI - Using Win-Win Strategies to Implement Health in All Policies: A Cross-Case Analysis. AB - BACKGROUND: In spite of increasing research into intersections of public policy and health, little evidence shows how policy processes impact the implementation of Health in All Policies (HiAP) initiatives. Our research sought to understand how and why strategies for engaging partners from diverse policy sectors in the implementation of HiAP succeed or fail in order to uncover the underlying social mechanisms contributing to sustainable implementation of HiAP. METHODS: In this explanatory multiple case study, we analyzed grey and peer-review literature and key informant interviews to identify mechanisms leading to implementation successes and failures in relation to different strategies for engagement across three case studies (Sweden, Quebec and South Australia), after accounting for the role of different contextual conditions. FINDINGS: Our results yielded no support for the use of awareness-raising or directive strategies as standalone approaches for engaging partners to implement HiAP. However, we found strong evidence that mechanisms related to "win-win" strategies facilitated implementation by increasing perceived acceptability (or buy-in) and feasibility of HiAP implementation across sectors. Win-win strategies were facilitated by mechanisms related to several activities, including: the development of a shared language to facilitate communication between actors from different sectors; integrating health into other policy agendas (eg., sustainability) and use of dual outcomes to appeal to the interests of diverse policy sectors; use of scientific evidence to demonstrate the effectiveness of HiAP; and using health impact assessment to make policy coordination for public health outcomes more feasible and to give credibility to policies being developed by diverse policy sectors. CONCLUSION: Our findings enrich theoretical understanding in an under-unexplored area of intersectoral action. They also provide policy makers with examples of HiAP across wealthy welfare regimes, and improve understanding of successful HiAP implementation practices, including the win-win approach. PMID- 26845570 TI - Extracellular Vesicles from BOEC in In Vitro Embryo Development and Quality. AB - To evaluate the effect of conditioned media (CM) and Extracellular Vesicles (EVs) derived from bovine oviduct epithelial cell (BOEC) lines on the developmental capacity of bovine zygotes and the quality of embryos produced in vitro, presumptive zygotes were cultured under specific conditions. In experiment 1, zygotes were cultured either on monolayers from BOEC extended culture (E), together with fresh BOEC suspension cells, or with BOEC-CM from fresh or E monolayers. In experiment 2, EVs were isolated from BOEC-CM and characterized (150-200 nm) by Nanosight(r) and electron microscopy. Zygotes were cultured in the presence of 3x10(5) EVs/mL, 1.5x10(5) EVs/mL or 7.5x10(4) EVs/mL of fresh or frozen BOEC-EVs. In experiment 3, zygotes were cultured in absence of FCS but with EVs from BOEC-E that had been cultured in different culture media. In experiment 4, zygotes were cultured in SOF+5% normal-FCS, or EV-depleted-FCS. In all cases, cleavage rate (Day 2) and blastocyst development (Day 7-9) was assessed. Blastocysts on Days 7/8 were used for quality evaluation through differential cell count, cryotolerance and gene expression patterns. No differences were found among all FCS-containing groups in cleavage rate or blastocyst yield. However, embryos derived from BOEC-CM had more trophectoderm cells, while embryos derived from BOEC-EVs, both fresh and frozen, has more trophectoderm and total cells. More embryos survived vitrification in the BOEC-CM and BOEC-EV groups. In contrast, more embryos survived in the EV-depleted-FCS than in normal-FCS group. Gene expression patterns were modified for PAG1 for embryos cultured with EVs in the presence of FCS and for IFN-T, PLAC8, PAG1, CX43, and GAPDH in the absence of FCS. In conclusion, EVs from FCS have a deleterious effect on embryo quality. BOEC-CM and EVs during in vitro culture had a positive effect on the quality of in vitro produced bovine embryos, suggesting that EVs have functional communication between the oviduct and the embryo in the early stages of development. PMID- 26845575 TI - Genome-Wide Analysis of Acute Endurance Exercise-Induced Translational Regulation in Mouse Skeletal Muscle. AB - Exercise dynamically changes skeletal muscle protein synthesis to respond and adapt to the external and internal stimuli. Many studies have focused on overall protein synthesis to understand how exercise regulates the muscular adaptation. However, despite the probability that each gene transcript may have its own unique translational characteristics and would be differentially regulated at translational level, little attention has been paid to how exercise affects translational regulation of individual genes at a genome-wide scale. Here, we conducted a genome-wide translational analysis using ribosome profiling to investigate the effect of a single bout of treadmill running (20 m/min for 60 min) on mouse gastrocnemius. Global translational profiles largely differed from those in transcription even at a basal resting condition as well as immediately after exercise. As for individual gene, Slc25a25 (Solute carrier family 25, member 25), localized in mitochondrial inner membrane and maintaining ATP homeostasis and endurance performance, showed significant up-regulation at translational level. However, multiple regression analysis suggests that Slc25a25 protein degradation may also have a role in mediating Slc25a25 protein abundance in the basal and early stages after acute endurance exercise. PMID- 26845576 TI - Eric, evolution and bodyplans. PMID- 26845578 TI - Potential of Synechocystis PCC 6803 as a novel cyanobacterial chassis for heterologous expression of enzymes in the trans-resveratrol biosynthetic pathway. AB - Selected model strains of phototrophic cyanobacteria have been genetically engineered for heterologous expression of numerous enzymes. In the present study, we initially explored the heterologous expression of enzymes involved in trans resveratrol production, namely, the production of tyrosine ammonia-lyase, coumaroyl CoA-ligase, and stilbene synthase, in the unicellular cyanobacterium Synechocystis PCC 6803. Under the promoters Ptrc1Ocore and Ptrc1O, the respective genes were transcribed and translated into the corresponding soluble proteins at concentrations of 16-34 MUg L(-1). The expression levels of these enzymes did not affect the growth rate of the cyanobacterial cells. Interestingly, coumaroyl CoA ligase expression slightly increased the chlorophyll a content of the cells. Overall, our results suggest that the complete pathway of trans-resveratrol production can be engineered in Synechocystis PCC 6803. PMID- 26845579 TI - Intracavernosal Prostaglandin Injection Prior to Circumcision Allows More Precise Removal of Foreskin. AB - OBJECTIVES: The study aims to evaluate the outcomes of adult circumcision with the use of intracavernosal injection (ICI) of prostaglandin to induce an erection at time of operation. METHODS: Twenty patients undergoing circumcision received ICI with prostaglandin prior to surgery. Demographics of all patients along with outcomes and complications at 2-week and 3-month follow-up were recorded. RESULTS: No complications were evident at 2-week and 3-month follow-up. All 20 patients were satisfied with cosmetic result. CONCLUSIONS: Circumcisions performed with ICI is a novel technique that allows accurate removal of foreskin and can be safely applied to current surgical technique for improved cosmetic results. PMID- 26845577 TI - An ancient dental gene set governs development and continuous regeneration of teeth in sharks. AB - The evolution of oral teeth is considered a major contributor to the overall success of jawed vertebrates. This is especially apparent in cartilaginous fishes including sharks and rays, which develop elaborate arrays of highly specialized teeth, organized in rows and retain the capacity for life-long regeneration. Perpetual regeneration of oral teeth has been either lost or highly reduced in many other lineages including important developmental model species, so cartilaginous fishes are uniquely suited for deep comparative analyses of tooth development and regeneration. Additionally, sharks and rays can offer crucial insights into the characters of the dentition in the ancestor of all jawed vertebrates. Despite this, tooth development and regeneration in chondrichthyans is poorly understood and remains virtually uncharacterized from a developmental genetic standpoint. Using the emerging chondrichthyan model, the catshark (Scyliorhinus spp.), we characterized the expression of genes homologous to those known to be expressed during stages of early dental competence, tooth initiation, morphogenesis, and regeneration in bony vertebrates. We have found that expression patterns of several genes from Hh, Wnt/beta-catenin, Bmp and Fgf signalling pathways indicate deep conservation over ~450 million years of tooth development and regeneration. We describe how these genes participate in the initial emergence of the shark dentition and how they are redeployed during regeneration of successive tooth generations. We suggest that at the dawn of the vertebrate lineage, teeth (i) were most likely continuously regenerative structures, and (ii) utilised a core set of genes from members of key developmental signalling pathways that were instrumental in creating a dental legacy redeployed throughout vertebrate evolution. These data lay the foundation for further experimental investigations utilizing the unique regenerative capacity of chondrichthyan models to answer evolutionary, developmental, and regenerative biological questions that are impossible to explore in classical models. PMID- 26845580 TI - Selective colorimetric and fluorescent quenching determination of uranyl ion via its complexation with curcumin. AB - Under pH4.0 HAc-NaAc buffer medium, curcumin alone possesses extraordinary weak fluorescence emission. Nevertheless, the introduction of Triton X-100 micelles can largely enhance the fluorescence intensity of curcumin. Uranyl ions can complex with micelles-capped curcumin, along with the slight red shift of curcumin fluorescence (about 1-7 nm), a clear decrement of absorbance (424 nm) and fluorescence (507 nm) intensities, and a distinct color change from bright yellow to orange. The fluorescence decrements (DeltaF, 507 nm) are positively correlated to the amount of uranyl ions in the concentration range of 3.7*10(-6) 1.4*10(-5) mol L(-1). The detection limit of this fluorescence quenching methods is 3.7*10(-6) mol L(-1), which is nearly 9000 times lower than the maximum allowable level in drinking water proposed by World Health Organization. Good selectivity is achieved because of a majority of co-existing substances (such as Ce(4+), La(3+), and Th(4+)) do not affect the detection. The content of uranyl ions in tap water samples was determined by the proposed method with satisfactory results. PMID- 26845581 TI - Simultaneous detection of trace metal ions in water by solid phase extraction spectroscopy combined with multivariate calibration. AB - Solid Phase Extraction Spectroscopy (SPES) developed in this paper is a technique to measure spectrum directly on the solid phase material where the analytes are concentrated in SPE process. Membrane enrichment and UV-Visible spectroscopy were utilized to fulfill SPES, and multivariate calibration method of partial least squares (PLS) was used to simultaneously detect the concentrations of trace cobalt (II) and zinc (II) in water samples. The proposed method is simple, sensitive and selective. The complexes of analyte ions were collected on the cellulose acetate membranes via membrane filtration after the complexation reaction with 1-2-pyridylazo 2-naphthol (PAN). The spectra of the membranes which contained the complexes of metal ions and PAN were measured directly without eluting. The analytical conditions including pH, reaction time, sample volume, the amount of PAN, and flow rates were optimized. Nonionic surfactant Brij-30 was absorbed on the membranes prior to SPES to modify the membranes for improving the enrichment and spectrum measurement. The interference from other ions to the determination was investigated. Under the optimal condition, the absorbance was linearly related to the concentration at the range of 0.1-3.0 MUg/L and 0.1-2.0 MUg/L, with the correlation coefficients (R(2)) of 0.9977 and 0.9951 for Co (II) and Zn (II), respectively. The limits of detection were 0.066 MUg/L for cobalt (II) and 0.104 MUg/L for zinc (II). PLS regression with leave-one-out cross validation was utilized to build models to detect cobalt (II) and zinc (II) in drinking water samples simultaneously. The correlation coefficient between ion concentration and spectrum of calibration set and independent prediction set were 1.0000 and 0.9974 for cobalt (II) and 1.0000 and 0.9956 for zinc (II). For cobalt (II) and zinc (II), the errors of the prediction set were in the range 0.0406 0.1353 MUg/L and 0.0025-0.1884 MUg/L. PMID- 26845582 TI - Novel pyridyl based azo-derivative for the selective and colorimetric detection of nickel(II). AB - A highly sensitive and selective pyridyl based colorimetric chemosensor (H2L) for the efficient detection of Ni(2+) has been reported. The synthesized chemosensor H2L is highly efficient in detecting Ni(2+) even in the presence of other metal ions that commonly co-exist with Ni(2+). H2L also shows distinct color change from green to deep red visible under naked eye due to specific binding with Ni(2+). This color change is due to formation of a new band at 510 nm upon gradual addition of Ni(2+). The association constant has been found to be 1.27*10(5) M(-1) with limit of detection (LOD) of 8.3*10(-7) M. Electronic structure of the H2L-Ni(2+) complex and sensing mechanism have been interpreted theoretically by DFT and TDDFT calculations. PMID- 26845583 TI - Miniaturized ionic liquid dispersive liquid-liquid microextraction in a coupled syringe system combined with UV for extraction and determination of danazol in danazol capsule and mice serum. AB - In this study, for the first time, a coupled 1-mL microsyringe system was utilized to perform a miniaturized ionic liquid dispersive liquid-liquid microextraction (IL-DLLME) method. Danazol was extracted and determined via the developed method followed by micro-volume ultraviolet spectroscopy (UV). The extraction process was carried out by the injection of extraction solvent ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate [C8mimPF6] into sample solution (syringe A), and then rapid shoot the solution into syringe B. After that the shooting was repeated several times at a rate of 1 cycle/s. The extraction procedure was induced by the formation of cloudy solution, which was composed of fine drops of [C8mimPF6] dispersed entirely into sample solution with the help of shooting without any dispersive solvent, ultrasonication or high temperature. Several important parameters affecting the extraction efficiency were studied and optimized. Under the optimized conditions, the limit of detection (LOD) was 0.055 MUg/mL (capsule) or 0.054 MUg/mL (serum) at a signal-to noise ratio of 3. The calibration curve was linear over the range of 0.62-25 MUg/mL. The proposed method was successfully applied to danazol capsule and the real mice serum samples and good spiked recoveries in the range of 90.5-103.4% were obtained. The obtained results of this work were in good agreement with the results of HPLC. PMID- 26845584 TI - Symmetrical N-acylsubstituted dihydrazones containing bithiophene core- Photophysical, electrochemical and thermal characterization. AB - Four symmetrical N-acylsubstituted dihydrazones containing bithiophene core were synthesized from condensation of 2,2'-bithiophene-5,5'-dicarboxyaldehyde with benzoic, isonicotinoyl, 2-thiophenic and 2-furoic hydrazide. The obtained compounds were characterized through the data from (1)H nuclear magnetic resonance spectroscopy (NMR), infrared spectroscopy (IR), elemental analysis, UV vis absorption spectroscopy, photoluminescence (PL), cyclic voltammetry (CV) and differential pulse voltammetry (DPV) measurements. Additionally, the electronic properties including orbital energies and resulting energy gaps were calculated by density functional theory (DFT). Their thermal behavior was investigated by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). They were thermal sable up to 320 degrees C. The prepared N-acylsubstituted dihydrazones emitted light with lambda(em) in the range of 499-530 nm in solution, whereas, in solid state as blend with PMMA blue emission was observed. They undergo quasi-reversible and irreversible electrochemical reduction and oxidation processes, respectively. Additionally, the selected compounds were tested preliminary as component of active layer in organic photovoltaic cells. The highest value of power conversion efficiency, equal to 1.68% under simulated 100 mW/cm(2) AM 1.5G irradiation was found for device with the architecture ITO/PEDOT:PSS/P3HT:PCBM:FBTH (1:2:2)/Al. PMID- 26845585 TI - Effect of Ar ion on the surface properties of low density polyethylene. AB - In this paper, low-density polyethylene (LDPE) was irradiated by argon ion with different fluences up to 10(15) ions/cm(2). The optical, chemical and hardness properties have been investigated using UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM) and micro indentation tester, respectively. The results showed the ion beam bombardment induced decreases in the transmittance of the irradiated polymer samples. This change in transmittance can be attributed to the formation of conjugated bonds i.e. possible formation of defects and/or carbon clusters. The indirect optical band gap decreased from 3.0 eV for the pristine sample to 2.3 eV for that sample irradiated with the highest fluence of the Ar ion beam. Furthermore, the number of carbon atoms and clusters increased with increasing Ar ion fluences. FTIR spectra showed the formation of new bands of the bombarded polymer samples. Furthermore, polar groups were created on the surface of the irradiated samples which refer to the increase of the hydrophilic nature of the surface of the irradiated samples. The Vicker's hardness increased from 4.9 MPa for the pristine sample to 17.9 MPa for those bombarded at the highest fluence. This increase is attributed to the increase in the crosslinking and alterations of the bombarded surface into hydrogenated amorphous carbon, which improves the hardness of the irradiated samples. The bombarded LDPE surfaces may be used in special applications to the field of the micro-electronic devices and shock absorbers. PMID- 26845586 TI - One pot synthesis, molecular structure and spectroscopic studies (X-ray, IR, NMR, UV-Vis) of novel 2-(4,6-dimethoxy-1,3,5-triazin-2-yl) amino acid ester derivatives. AB - Novel series of 2-(4,6-dimethoxy,1,3,5-triazin-2-yl) amino acid ester derivatives were synthesized using simple one pot method in methanol. The products were obtained in high yields and purities as observed from their spectral data, elemental analyses, GC-MS and X-ray crystallographic analysis. The B3LYP/6 311G(d,p) calculated molecular structures are well correlated with the geometrical parameters obtained from the X-ray analyses. The spectroscopic properties such as IR vibrational modes, NMR chemical shifts and UV-Vis electronic transitions were discussed both experimentally and theoretically. The IR vibrational frequencies showed good correlations with the experimental data (R(2)=0.9961-0.9995). The electronic spectra were assigned based on the TD-DFT results. Intense electronic transition band is calculated at 198.1 nm (f=0.1389), 204.2 nm (f=0.2053), 205.0 (f=0.1704) and 205.7 (0.2971) for compounds 6a-i, respectively. The molecular orbital energy levels contributed in the longest wavelength transition band were explained. For all compounds, the experimental wavelengths showed red shifts compared to the calculations due to the solvent effect. The NMR chemical shifts were calculated using GIAO method. The NBO analyses were performed to predict the stabilization energies due to the electron delocalization processes occur in the studied systems. PMID- 26845587 TI - Paul Ehrlich (1854-1915) and His Contributions to the Foundation and Birth of Translational Medicine. AB - Translational research and precision medicine are based on a profound knowledge of cellular and molecular mechanisms contributing to various physiologic processes and pathologic reactions in diverse organs. Whereas specific molecular interactions and mechanisms have been identified during the past 5 decades, the underlying principles were defined much earlier and originate from to the seminal observations made by outstanding researchers between 1850 and 1915. One of the most outstanding exponents of these scientists is Paul Ehrlich. His work resulted not only in the foundation and birth of modern hematology and immunology, but also led to the development of chemotherapy and specific targeted treatment concepts. In 2015, the Medical University of Vienna organized a memorial meeting, with the aim of honoring Paul Ehrlich's contributions to science, and to commemorate the 100th anniversary of his death. The authors of the current review served as faculty members and dedicate this paper to Paul Ehrlich and his remarkable contributions to medicine. PMID- 26845588 TI - Association Study of 60 Candidate Genes with Antipsychotic-induced Weight Gain in Schizophrenia Patients. AB - INTRODUCTION: This study aimed to investigate the association of multiple candidate genes with weight gain and appetite change during antipsychotic treatment. METHODS: A total of 233 single nucleotide polymorphisms (SNPs) within 60 candidate genes were genotyped. BMI changes for up to 8 weeks in 84 schizophrenia patients receiving antipsychotic medication were analyzed using a linear mixed model. In addition, we assessed appetite change during antipsychotic treatment in a different group of 46 schizophrenia patients using the Drug Related Eating Behavior Questionnaire. RESULTS: No SNP showed a statistically significant association with BMI or appetite change after correction for multiple testing. We observed trends of association (P<0.05) between 19 SNPs of 11 genes and weight gain, and between 7 SNPs of 5 genes and appetite change. In particular, rs696217 in GHRL showed suggestive evidence of association with not only weight gain (P=0.001) but also appetite change (P=0.042). Patients carrying the GG genotype of rs696217 exhibited higher increase in both BMI and appetite compared to patients carrying the GT/TT genotype. DISCUSSION: Our findings suggested the involvement of a GHRL polymorphism in weight gain, which was specifically mediated by appetite change, during antipsychotic treatment in schizophrenia patients. PMID- 26845589 TI - Comparing Nalmefene and Naltrexone in Alcohol Dependence: Are there any Differences? Results from an Indirect Meta-Analysis. AB - BACKGROUND: The mu-opioid antagonist naltrexone is one of the few approved pharmacotherapies for the treatment of alcohol dependence. Recently, the mu opioid antagonist and partial kappa agonist nalmefene was approved by the European Medicines Agency for the reduction of alcohol consumption in adult patients with alcohol dependence. To date, no head-to-head studies have compared the efficacy and safety of naltrexone and nalmefene in reducing alcohol consumption. METHODS: An indirect meta-analysis of randomized controlled studies on these 2 medications was conducted. A random effects model was used to measure effects and compare the 2 medications. 4 placebo-controlled studies with nalmefene and 13 with naltrexone were included. RESULTS: A statistically significant advantage of nalmefene towards naltrexone in the 2 patient-relevant outcome efficacy criteria, quantity and frequency of drinking, was found. Both drugs had a benign safety profile. CONCLUSIONS: This indirect meta-analysis indicates an advantage of nalmefene over naltrexone. Nalmefene is an effective and well-tolerated medication for the reduction of alcohol consumption. Additional data are necessary to demonstrate possible advantages of nalmefene over naltrexone in the treatment of alcohol dependence. PMID- 26845590 TI - Association between learning style preferences and anatomy assessment outcomes in graduate-entry and undergraduate medical students. AB - An improved understanding of the relationship between anatomy learning performance and approaches to learning can lead to the development of a more tailored approach to delivering anatomy teaching to medical students. This study investigated the relationship between learning style preferences, as measured by Visual, Aural, Read/write, and Kinesthetic (VARK) inventory style questionnaire and Honey and Mumford's learning style questionnaire (LSQ), and anatomy and clinical skills assessment performance at an Irish medical school. Additionally, mode of entry to medical school [undergraduate/direct-entry (DEM) vs. graduate entry (GEM)], was examined in relation to individual learning style, and assessment results. The VARK and LSQ were distributed to first and second year DEM, and first year GEM students. DEM students achieved higher clinical skills marks than GEM students, but anatomy marks did not differ between each group. Several LSQ style preferences were shown to be weakly correlated with anatomy assessment performance in a program- and year-specific manner. Specifically, the "Activist" style was negatively correlated with anatomy scores in DEM Year 2 students (rs = -0.45, P = 0.002). The "Theorist" style demonstrated a weak correlation with anatomy performance in DEM Year 2 (rs = 0.18, P = 0.003). Regression analysis revealed that, among the LSQ styles, the "Activist" was associated with poorer anatomy assessment performance (P < 0.05), while improved scores were associated with students who scored highly on the VARK "Aural" modality (P < 0.05). These data support the contention that individual student learning styles contribute little to variation in academic performance in medical students. Anat Sci Educ 9: 391-399. (c) 2016 American Association of Anatomists. PMID- 26845592 TI - Concordance of sustained virologic response at weeks 4, 12 and 24 post-treatment of hepatitis c in the era of new oral direct-acting antivirals: A concise review. AB - The goal of treatment for chronic hepatitis C viral (HCV) infection is to cure the infection rather than suppress the virus. Historically, a sustained virological response (SVR) defined as undetectable HCV RNA at 24 weeks following the completion of treatment was considered the gold standard to define successful eradication of the virus as a primary endpoint in clinical trials. SVR measured at 12 weeks post-treatment has been shown to be highly concordant with SVR24 in trials of pegylated interferon and ribavirin. The appropriateness and durability of SVR12 as the efficacy endpoint with new oral direct-acting antivirals is less established. A literatura search was performed using PubMed, EMBASE and CENTRAL databases to identify any studies that examined the concordance between SVR24 and earlier time points. Two studies and 4 abstracts were found that performed concordance analyses using positive and negative predictive values. Overall, SVR4 and SVR12 were highly concordant with SVR24 with high positive (> 97%) and negative (> 94%) predictive values; however there was a higher risk of HCV relapse occurring after post-treatment week 4. The majority of the data focused on SVR12 and demonstrated that SVR12 reliably predicted SVR24 in several populations infected with HCV (treatment-naive, prior null responders, different genotypes) using various new oral direct-acting antiviral regimens. In conclusion, the available data suggests that SVR12 is a reliable assessment of HCV eradication and could be used instead of SVR24 for drug development clinical trials assessing efficacy of new direct-acting antivirals. Data on the long-term durability of SVR12 is still needed. PMID- 26845593 TI - Redox state and methods to evaluate oxidative stress in liver damage: From bench to bedside. AB - Oxidative stress is importantly involved in the pathophysiology of various liver diseases. The redox state participates on the course of the inflammatory, metabolic and proliferative liver diseases. The main sources of the reactive oxygen species (ROS) are represented by the mitochondria and cytochrome P450 enzymes in the hepatocyte, Kupffer cells and neutrophils. Cells are provided with efficient molecular strategies to strictly control the intracellular ROS level and to maintain the balance between oxidant and antioxidant molecules. Hepatocyte's proteins, lipids and DNA are among the cellular structures to be affected primarily by ROS and reactive nitrogen species (RNS). This process disrupts at cellular and molecular level the structure-function relationship on liver cells at different sites. Therefore, further studies on the molecular mechanisms of the oxidative stress pathways on liver diseases are urgently required, because they could explain the pathogenesis of various liver disorders. Moreover, new methods to evaluate oxidative stress like the oxidative markers among hepatocytes offers the potential to diagnose the degree of liver injury and ultimately to assess the response to pharmacological therapies. In this review, we discuss the molecular, metabolic and aging aspects of the oxidative stress, and the methods to evaluate oxidative stress on liver damage. PMID- 26845594 TI - Effect of entecavir on CD4+ T-cell subpopulations in patients with chronic hepatitis B. AB - Background and aims. CD4+ T cells play an important role in response to hepatitis B virus (HBV) infection. We investigated the change in CD4+ T-cell subpopulations and viral load in patients with chronic HBV infection who were treated with entecavir. MATERIAL AND METHODS: Thirty patients with chronic HBV infection were enrolled according to the criteria recommended by the Chinese Society of Infectious Diseases and the Chinese Society of Hepatology. The expressions of signature transcription factors and cytokines of CD4+ T-cell subpopulations were measured in chronic hepatitis B (CHB) patients treated with entecavir treatment. RESULTS: Entecavir treatment significantly attenuated hepatitis B virus DNA load and affected the CD4+ T-cell subsets in CHB patients. A dramatic decrease in the Th17 and Treg cell frequencies and expressions of their related cytokines were found in CHB patients with entecavir treatment. In contrast, entecavir treatment caused a remarkable increase in the Th2 cell frequencies and expressions of their related cytokines. CONCLUSION: Our results suggested that Th17 and Treg cells were the more sensitive subtypes to entecavir- induced inhibition of HBV replication compared to Th1 and Th2 cells in chronic HBV patients. PMID- 26845595 TI - Alcoholic liver disease presents at advanced stage and progresses faster compared to non-alcoholic fatty liver diseas. AB - BACKGROUND AND OBJECTIVE: Steatohepatitis is a common cause of liver disease due to alcohol (ALD) or non-alcoholic fatty liver disease (NAFLD). We performed this study to compare natural history of ALD and NAFLD. MATERIAL AND METHODS: Retrospective analysis of ALD or NAFLD patients managed at our center (2007 2011). ALD diagnosed by excluding other liver diseases (except HCV) and alcohol abuse of > 40 g/d in women and > 60 g/d in men for > 5 years. NAFLD diagnosed by excluding other liver diseases and a history of alcohol use of < 10 g/d. Cirrhosis was diagnosed using biopsy for uncertain clinical diagnosis. RESULTS: Compared to patients with NAFLD (n = 365; mean age 50 yrs; 43% males; 53% diabetic), ALD patients (n = 206; mean age 51 yrs; 68% males; 24% diabetic) presented more often with cirrhosis or complications(46vs. 12%; P< 0.0001) with a higher MELD score (13 +/- 7 vs. 8 +/- 8; P<0.0001). On logistic regression, ALD diagnosis was associated with presence of cirrhosis by over 4-fold (4.1 [1.8 9.1]) even after excluding 23 patients with concomitant HCV. Over median follow up of about 3 and 4 yrs among ALD and NAFLD patients respectively, ALD patients more frequently developed cirrhosis or its complications including HCC with worse transplant free survival (90 vs. 95%; P = 0.038). CONCLUSIONS: Compared to NAFLD, ALD patients present at an advanced stage of liver disease with a faster progression on follow-up. Prospective multicenter studies are needed to identify potential barriers to early referral of ALD patients as basis for development of strategies to improve outcome of patients with ALD. PMID- 26845596 TI - Gene expression profiling reveals key genes and pathways related to the development of non-alcoholic fatty liver disease. AB - Background. This study aims to identify key genes and pathways involved in non alcoholic fatty liver disease (NAFLD). MATERIAL AND METHODS: The dataset GSE48452 was downloaded from Gene Expression Omnibus, including 14 control liver samples, 27 healthy obese samples, 14 steatosis samples and 18 nonalcoholic steatohepatitis (NASH) samples. Differentially expressed genes (DEGs) between controls and other samples were screened through LIMMA package. Then pathway enrichment analysis for DEGs was performed by using DAVID, and alterations of enriched pathways were determined. Furthermore, protein-protein interaction (PPI) networks were constructed based on the PPI information from HPRD database, and then, networks were visualized through Cytoscape. Additionally, interactions between microRNAs (miRNAs) and pathways were analyzed via Fisher's exact test. RESULTS: A total of 505, 814 and 783 DEGs were identified for healthy obese, steatosis and NASH samples in comparison with controls, respectively. DEGs were enriched in ribosome (RPL36A, RPL14, etc.), ubiquitin mediated proteolysis (UBE2A, UBA7, etc.), focal adhesion (PRKCA, EGFR, CDC42, VEGFA, etc.), Fc?R mediated phagocytosis (PRKCA, CDC42, etc.), and so on. The 27 enriched pathways gradually deviated from baseline (namely, controls) along with the changes of obese-steatosis-NASH. In PPI networks, PRKCA interacted with EGFR and CDC42. Besides, hsa-miR-330-3p and hsa-miR-126 modulated focal adhesion through targeting VEGFA and CDC42. CONCLUSIONS: The identified DEGs (PRKCA, EGFR, CDC42, VEGFA), disturbed pathways (ribosome, ubiquitin mediated proteolysis, focal adhesion, Fc?R-mediated phagocytosis, etc.) and miRNAs (hsa-miR-330-3p, hsa-miR 126, etc.) might be closely related to NAFLD progression. These results might contribute to understanding NAFLD mechanism, conducting experimental researches, and designing clinical practices. PMID- 26845598 TI - Good outcomes of liver transplantation for hepatitis C at a low volume centre. AB - BACKGROUND AND AIMS: Concerns exist about outcomes of liver transplantation (LT) from low volume centres, especially for hepatitis C (HCV) patients. The aim of the study was to assess patient outcomes as well as their predictors post LT for HCV in a small volume Australian unit (< 25 LTs/year), comparing these with the average outcomes obtained from national and international transplant registries. Patients transplanted for HCV at the South Australian Liver Transplant Unit between 1992 and 2012 were studied. Outcomes assessed were patient and graft survival at 1,3, and 5 years. Factors independently associated with the outcomes were assessed using Cox regression model. RESULTS: 1, 3, and 5-year patient survival for HCV patients was 95.2, 82.9, and 78.2%, graft survival were 93.7, 80.1, and 75.5% respectively. The total follow-up time observed was 299.9 years amongst 61 patients in which there were 16 deaths. The expected number of deaths was 40.4 and the standardized mortality ratio 0.40 (95% CI = 0.24, 0.65). These results compared favourably to those obtained from the SRTR registry. Variables independently associated with lower patient survival: donor age (HR = 1.06, 95% CI 1.02 - 1.11; P = 0.003), and post LT cytomegalovirus (CMV) disease requiring treatment (HR = 4.03, 95% CI 1.48 - 10.92;P = 0.06). CONCLUSION: In conclusion, high rates of patient and graft survival for HCV liver transplantation can be obtained in a small volume unit. Young donor age and lack of CMV disease post transplant were associated with better outcomes. Institutional factors may be influential determinants of outcomes. PMID- 26845597 TI - Usefulness of acoustic radiation force impulse and fibrotest in liver fibrosis assessment after liver transplant. AB - Background and rationale. Acoustic radiation force impulse (ARFI) is a non invasive tool used in the evaluation of liver fibrosis in HCV positive immune competent patients. This study aimed to assess the accuracy of ARFI in discriminating liver transplanted patients with different graft fibrosis severity and to verify whether ARFI, eventually combined with non-invasive biochemical tests, could spare liver biopsies. This prospective study included 51 HCV positive liver transplanted patients who consecutively underwent to annual liver biopsy concomitantly with ARFI and blood chemistry tests measurements needed to calculate several non-invasive liver fibrosis tests. RESULTS: Overall ARFI showed an AUC of 0.885 in discriminating between patients without or with significant fibrosis (Ishak score 0-2vs. 3-6). Using a cut-off of 1.365 m/s, ARFI possesses a negative predictive value of 100% in identifying patients without significant fibrosis. AUC for Fibrotest was 0.848 in discriminating patients with Ishak fibrosis score 0-2 vs. 3-6. The combined assessment of ARFI and Fibro-test did not improve the results obtained by ARFI alone. CONCLUSION: ARFI measurement in HCV positive liver transplanted patients can be considered an easy and accurate non-invasive tool in identify patients with a benign course of HCV recurrence. PMID- 26845599 TI - Hepatic immunohistochemistry of bile transporters in progressive familial intrahepatic cholestasis. AB - Background. Diagnosis of progressive familial intrahepatic cholestasis (PFIC) is a challenging matter that involves the summation of clinical, laboratory, radiological, and liver histological parameters; in addition to specific investigations to exclude other causes of neonatal cholestasis. The aim of this study was to evaluate liver tissue immunohistochemistry of bile salt export pump (BSEP) and multidrug resistance 3 (MDR3) proteins in differentiating PFIC from other causes of neonatal cholestasis, particularly, when genotyping is unavailable. MATERIAL AND METHODS: The study included 25 patients diagnosed phenotypically as PFIC including 2 with PFIC1, 17 with PFIC2 and 6 with PFIC3. A second group of 25 cholestatic newborns with confirmed etiologies other than PFIC, termed as non-PFIC, included as controls. Liver biopsies from all patients were obtained and immunostained for BSEP and MDR3. RESULTS: Negative immunoreaction of BSEP and MDR3 was found in the majority of PFIC group (76 and 64% respectively). Nonetheless, the negative immunoreaction was demonstrated in a considerable number of the non-PFIC group. BSEP immunoreaction was negative in the majority (82.4%) of PFIC2 but in none of the two patients with PFIC1. In addition, negative MDR3 immunoreaction was more frequently associated with PFIC3 compared to non-PFIC group. CONCLUSION: MDR3 and BSEP immunostaining would be a helpful tool in supporting the phenotypic diagnosis of PFIC subtypes and in differentiating PFIC from other causes of neonatal cholestasis. PMID- 26845600 TI - What constitutes liver failure after transjugular intrahepatic portosystemic shunt creation? A proposed definition and grading system. AB - Background and rationale for the study. There is currently no definition of post transjugular intrahepatic portosystemic shunt (TIPS) liver failure (PTLF), which constitutes a barrier to standardization of TIPS results reporting and limits the ability to compare liver failure incidence across clinical studies. Thisdescriptive study proposes and preliminarily tests the performance of a PTLF definition and grading system. RESULTS: PTLF was defined by >= 3-fold bilirubin and/or >= 2-fold INR elevation associated with clinical outcomes of prolonged hospitalization/increase in care level (grade 1), TIPS reduction or liver transplantation (grade 2), or death (grade 3) within 30-days of TIPS. PTLF incidence was 20% (grades 1, 2, 3: 10%, 3%, 8%) among 270 TIPS cases, and the scheme identified patients at increased risk for morbidity and mortality with a statistically significant difference in clinical outcomes between PTLF and non PTLF groups (P<0.0001). CONCLUSIONS: In conclusion, the PTLF definition and classification scheme put forth distributes patients into unique risk groups. PTLF grading may thus be useful for standardization of TIPS results reporting. PMID- 26845601 TI - External validation and comparison of six prognostic models in a prospective cohort of HBV-ACLF in China. AB - Background. Acute-on-chronic liver failure has high mortality. Currently, robust models for predicting the outcome of hepatitis B virus (HBV)-associated ACLF are lacking. AIM: To assess and compare the performance of six prevalent models for short- and longterm prognosis in patients with HBV-ACLF. MATERIAL AND METHODS: The model for end-stage liver disease (MELD), MELD sodium (MELD-Na), MELD to sodium ratio (MESO), integrated MELD, Child-Turcotte-Pugh (CTP), and modified CTP (mCTP) were validated in a prospective cohort of 232 HBV-ACLF patients. The six models were evaluated by determining discrimination, calibration and overall performance at 3 months and 5 years. RESULTS: According to the Hosmer-Lemeshow tests and calibration plots, all models could adequately describe the data except CTP at 3 months. Discrimination analysis showed that the iMELD score had the highest AUC of 0.76 with sensitivity of 62.6% and specificity of 80.2% for an optimal cut-off value of 52 at 3 months. It also had the highest AUC of 0.80 with sensitivity of 89.9% and specificity of 48.2% for an optimal cut-off value of 43 at 5 years. The overall performance of iMELD, assessed with Nagelkerke's R2 and the Brier score, was also the best among the six models. CONCLUSION: Integrated MELD may be the best model to predict short- and long-term prognosis in patients with HBV-ACLF. PMID- 26845602 TI - Alkaline phosphatase normalization is a biomarker of improved survival in primary sclerosing cholangitis. AB - Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis. MATERIAL AND METHODS: This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses. RESULTS: Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint free survival. CONCLUSIONS: Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis. PMID- 26845603 TI - Clinical characteristics of liver failure from a systemic cause: A report from an advanced critical care center. AB - Background/Purpose. In Japan, acute liver failure (ALF) has generally been described using the diagnostic term, "fulminant hepatitis", because of the fact that most cases of ALF has been thought to occur in association with hepatitis mainly due to a hepatitis virus infection. New diagnostic criteria for ALF, including ALF other than fulminant hepatitis, were established in 2011. We therefore examined the prognostic factors of patients with liver failure from a systemic cause, including warfarin users. MATERIAL AND METHODS: Sixty-six patients with ALF that were diagnosed according to the Japanese diagnostic criteria for ALF between 2009 and 2013 were divided into a survivor group and a non-survivor group. The data regarding demography, liver tests, coagulation tests, Sequential Organ Failure Assessment (SOFA) scores, and the use of oral warfarin or aspirin were compared between the two groups. RESULTS: The SOFA score was significantly higher in the non-survivor group (p = 0.025). The proportion of oral warfarin users was significantly higher in the survivor group (p = 0.013) (58.1% vs. 26.1%). A multivariate logistic regression analysis showed the SOFA score (odds ratio: 0.851, 95% confidence interval (CI): 0.728-0.995, p = 0.043) and warfarin use (odds ratio: 3.261, 95% CI: 1.028-10.347, p = 0.045) to be significant factors that were negatively and positively associated with the prognosis, respectively. CONCLUSION: In this study, among the patients with ALF other than fulminant hepatitis, those with a high SOFA score on admission exhibited a poor prognosis. In addition, oral warfarin use prior to disease onset was found to be a factor which indicated a good prognosis. PMID- 26845604 TI - IL-1beta siRNA adenovirus benefits liver regeneration by improving mesenchymal stem cells survival after acute liver failure. AB - BACKGROUND: Uncontrolled hapatic inflammatory response is regarded as the primary pathological mechanism of acute liver failure and impairs the regeneration of hepatocytes and stem cell grafts. Interleukin-1 plays a key role for activating immune and inflammatory response. Recently, siRNA has made quite a few progresses in treating inflammatory response. AIM: To assess the effect of IL 1? siRNA adenovirus on MSC and the therapeutic effect of MSC combined with IL-1? siRNA adenovirus in ALF. MATERIAL AND METHODS: We implanted MSC or/and IL-1? siRNA adenovirus via the tail vein, using CCl4-induced ALF in a mice model. Mice were sacrificed at different time points. Blood samples and liver tissues were collected. Hepatic injury, liver regeneration, cytokines (CXCL1, IL-1?, IL-10, IL 6, VEGF and HGF), animal survival and vital MSC were assessed after cell transplantation. RESULTS: MSC combined with IL-1? siRNA reduced the inflammatory levels and prevented liver failure. These animals administrated with MSC and IL 1? siRNA also exhibited improved liver regeneration and increased survival rates. Immunohistochemistry and fluorescence microscopy revealed the number of vital MSC in ALF + MSC + IL-1? siRNA group were significantly more than that in ALF + MSC group. CONCLUSION: IL-1? siRNA adenovirus could enhance MSC ability of tissue regeneration through increasing its survival rate. Accordingly, combination of IL 1? siRNA adenovirus and MSC had a synergistic effect on acute liver failure. PMID- 26845605 TI - Ectopic varices: Hidden challenges in the vascular anatomy. PMID- 26845606 TI - Tenofovir-induced Fanconi syndrome in a patient with chronic hepatitis B monoinfection. AB - Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor indicated for treatment of patients with chronic hepatitis B virus (CHB) and human immunodeficiency virus (HIV) infections. Despite the good safety profile of the drug, Fanconi syndrome is a possible adverse reaction of TDF treatment, especially in HIV-infected patients. Only a few cases have been reported in patients with CHB-monoinfections. This report presents a case of a 58 year-old man with mild HBeAg-negative CHB who was exposed to TDF and developed drug-induced Fanconi syndrome. Renal dysfunction reverted after TDF discontinuation and a switch to entecavir, and viral replication remained suppressed. A literature review yielded six additional cases of TDF-induced Fanconi syndrome, all with risk factors for renal dysfunction despite the patients having normal glomerular filtration rates. We discuss the overall risk for Fanconi syndrome in CHB-monoinfected patients exposed to TDF and the importance of careful monitoring of glomerular and tubular functions even when pre-existing kidney disease is not present. PMID- 26845607 TI - Monozygotic twins with NASH cirrhosis: cumulative effect of multiple single nucleotide polymorphisms? AB - Multiple genetic and environmental factors interact to determine an individual's predisposition to non-alcoholic fatty liver disease and its phenotypic characteristics. Association studies have found a number of alleles associated with the development of non-alcoholic steatohepatitis. Our aim was to investigate whether multiple risk-associated alleles may be present in affected monozygotic twins, indicating underlying genetic predisposition to non-alcoholic steatohepatitis. We determined the genotype of 14 candidate gene polymorphisms (at 11 unlinked loci) in a set of monozygotic twins who presented with cirrhosis within 18 months of each other. Genotyping revealed multiple single nucleotide polymorphisms at 9 independent loci in genes PNPLA3, APOC3, GCKR, TRIB1, LYPLAL1, PPP1R3B, COL13A1, and EFCAB4B, previously implicated in contributing to non alcoholic steatohepatitis pathogenesis. In conclusion, this case series illustrates the potential cumulative effect of multiple polymorphisms in the development and potential progression of a complex trait such as NASH cirrhosis. PMID- 26845608 TI - Cystic angiosarcoma of the liver. A previously undescribed neoplasm. AB - We report an example of a cystic hepatic angiosarcoma that to our knowledge has not been previously described. The patient was a 70 year old woman who was admitted to the emergency room because of hypovolemic shock. A computed tomography showed four heterogeneous hepatic cystic masses varying from 2.5 to 11.2 cm; one of these with rupture and formation of a subcapsular hematoma. The cyst wall was lined by several layers of neoplastic epithelioid and spindle shaped endothelial cells that in some areas extended to the underlying stroma. They expressed CD31 and CD34, and were negative for cytokeratin. The patient is alive with residual hepatic cystic angiosarcoma. However, follow up is too short to be significant. PMID- 26845609 TI - Insulin treatment of people with diabetes mellitus and chronic liver disease. PMID- 26845610 TI - Report of the Baveno VI Consensus Workshop. PMID- 26845611 TI - Dual oxidases participate in the regulation of intestinal microbiotic homeostasis in the kuruma shrimp Marsupenaeus japonicus. AB - The metazoan gut lumen harbors numerous microbial communities. Tolerance for high bacterial counts and maintenance of microbiota homeostasis remain insufficiently studied. In this study, we identified a novel dual oxidase (MjDUOX2) involved in reactive oxygen species (ROS) production in the kuruma shrimp Marsupenaeus japonicus. MjDUOX2 is a transmembrane protein with an N-signal peptide region (19 aa) and a peroxidase homology domain (PHD, 554 aa) in the extracellular region; seven transmembrane regions; and three EF (calcium-binding region) domains (110 aa), a FAD-binding domain (104 aa), and a NAD-binding domain (156 aa) in the intracellular region. The novel MjDUOX2 exhibits a relatively low similarity (26.84% identity) to a previously reported DUOX in the shrimp (designated as MjDUOX1). The mRNA of MjDUOXs was widely distributed in the hemocytes, heart, hepatopancreas, gills, stomach, and intestine. Oral infection of the shrimp with pathogenic bacteria upregulated the mRNA expression of MjDUOXs and increased the ROS level in the intestine. However, High ROS level could inhibit the expression of MjDUOXs in shrimp after Vibrio anguillarum infection. Knockdown of MjDUOXs by RNA interference (RNAi) decreased the ROS level, increased the bacterial count in the intestine, and decreased the survival rate of the MjDUOX-RNAi shrimp infected with V. anguillarum. These results suggest that MjDUOXs play an important role for microbiota homeostasis in intestine of shrimp. PMID- 26845613 TI - Burden of disease of dietary exposure to acrylamide in Denmark. AB - Acrylamide (AA) is a process-contaminant that potentially increases the risk of developing cancer in humans. AA is formed during heat treatment of starchy foods and detected in a wide range of commonly consumed products. Increased focus on risk ranking and prioritization of major causes of disease makes it relevant to estimate the impact that exposure to chemical contaminants and other hazards in food have on health. In this study, we estimated the burden of disease (BoD) caused by dietary exposure to AA, using disability adjusted life years (DALY) as health metric. We applied an exposure-based approach and proposed a model of three components: an exposure, health-outcome, and DALY-module. We estimated BoD using two approaches for estimating cancer risk based on toxicological data and two approaches for estimating DALY. In Denmark, 1.8 healthy life years per 100.000 inhabitants are lost each year due to exposure to AA through foods, as estimated by the most conservative approach. This result should be used to inform risk management decisions and for comparison with BoD of other food-borne hazards for prioritizing policies. However, our study shows that careful evaluation of methodological choices and assumptions used in BoD studies is necessary before use in policy making. PMID- 26845612 TI - Anti-obesity effects of seaweeds of Jeju Island on the differentiation of 3T3-L1 preadipocytes and obese mice fed a high-fat diet. AB - The seaweeds were collected from the coast of Jeju Island, South Korea. We investigated ethanol extracts from seaweed as potential antiobesity agents by testing their effect on adipogenic differentiation in 3T3-L1 cells. Among the red algae extracts tested, the Plocamium telfairiae extract (PTE) showed the highest inhibitory effect on lipogenesis in adipocytes and, thus, was selected as a potential antiobesity agent. PTE treatment significantly decreased the expression of the adipogenic-specific proteins peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein-alpha, sterol regulatory element-binding protein 1, and fatty acid-binding protein 4 compared with that in the untreated 3T3-L1 cells. PTE also inhibited high-fat diet (HFD)-induced obesity in male C57BL/6 mice. Oral administration of PTE significantly reduced the body weight, fatty liver, amount of white adipose tissue, and levels of triglyceride and glucose in the tested animals. Taken together, these data demonstrate that PTE can be developed as a therapeutic agent for obesity. PMID- 26845614 TI - Development and maturation of natural killer cells. AB - Natural killer (NK) cells are innate lymphocytes that are critical for host protection against pathogens and cancer due to their ability to rapidly release inflammatory cytokines and kill infected or transformed cells. In the 40 years since their initial discovery, much has been learned about how this important cellular lineage develops and functions. We now know that NK cells are the founding members of an expanded family of lymphocyte known as innate lymphoid cells (ILC). Furthermore, we have recently discovered that NK cells can possess features of adaptive immunity such as antigen specificity and long-lived memory responses. Here we will review our current understanding of the molecular mechanisms driving development of NK cells from the common lymphoid progenitor (CLP) to mature NK cells, and from activated effectors to long-lived memory NK cells. PMID- 26845616 TI - Do glutathione levels decline in aging human brain? AB - For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. PMID- 26845615 TI - AID hits the jackpot when missing the target. AB - Activation induced deaminase is the single B cell specific factor mediating class switch recombination and somatic hypermutation. Numerous studies have shown that AID preferentially targets Ig substrates and also attacks non-Ig substrates to create DNA damage that contributes to lymphomagenesis. AID targeting to Ig loci is linked to transcription but the mechanism governing this process has been obscure. Here we discuss research that illustrates the connection between AID targeting to DNA substrates and transcription processes to reveal rules governing the specificity of AID attack. These observations are woven together to provide a integrated view of AID function and a surprising linkage with global regulation of gene expression. PMID- 26845617 TI - Lipoxin A4 attenuates LPS-induced mouse acute lung injury via Nrf2-mediated E cadherin expression in airway epithelial cells. AB - A fundamental element of acute lung injury (ALI) is the inflammation that is part of the body's immune response to a variety of local or systemic stimuli. Lipoxins (LXs) are important endogenous lipids that mediate resolution of inflammation. Previously, we demonstrated that LXA4 reduced the LPS inhalation-induced pulmonary edema, neutrophil infiltration and TNF-alpha production in mice. With the same model, the current investigation focused on the role of the airway epithelium, a first-line barrier and a prime target of inhaled toxicants. We report that LXA4 strongly inhibited LPS-induced ALI in mice, in part by protecting the airway epithelium and preserving the E-cadherin expression and airway permeability. Using a cryo-imaging assay and fluorescence detection, LXA4 was shown to block LPS-induced ROS generation and preserve mitochondrial redox status both in vivo and in vitro. To further assess whether and how NF-E2-related factor 2 (Nrf2) was involved in the protective effect of LXA4, fluorescence resonance energy transfer (FRET) analysis was employed in human epithelial cell line (16HBE), to determine the relative distance between Nrf2 and its negative regulator or cytosolic inhibitor, Kelch-like ECH-associated protein 1 (Keap1). It provided us the evidence that LXA4 further promoted the dissociation of Nrf2 and Keap1 in LPS-treated 16HBE cells. The results also showed that LXA4 activates Nrf2 by phosphorylating it on Ser40 and triggering its nuclear translocation. Moreover, when the plasmid expression dominant negative mutation of Nrf2 was transfected as an inhibitor of wild-type Nrf2, the protective effect of LXA4 on E cadherin expression was almost completely blocked. These results provide a new mechanism by which LXA4 inhibits LPS-induced ALI through Nrf2-mediated E-cadherin expression. PMID- 26845618 TI - Fogarty and Charge of Moral Imperialism: A Response to Hellmann et al. PMID- 26845620 TI - Product Channels in the Reaction of the Hydroxymethyl Radical with Nitric Oxide. AB - The products of the reaction of CH2OH with NO were studied by infrared diode laser spectroscopy. Products were detected to determine the branching ratios of the CH2OH + NO reaction. HNCO was detected in 10.3 +/- 2% yields. No other products were detected in significant quantities, indicating that adduct formation is the primary reaction pathway. Ab initio calculations of the potential energy surface show a low energy pathway to HNCO + H2O, but no other bimolecular channels, in agreement with the experiments. PMID- 26845619 TI - Moral Imperialism in NIH Fogarty Training Program and the Continuing Unethical Trials in Poor Countries: A Rejoinder. PMID- 26845621 TI - Corrigendum to "The cytochrome c peroxidase and cytochrome c encounter complex: The other side of the story" [FEBS Lett. 588 (2014) 1873-1878]. PMID- 26845624 TI - Male non-gonococcal urethritis: From microbiological etiologies to demographic and clinical features. AB - OBJECTIVES: To detect microorganisms responsible for male acute urethritis and to define the microbiology of non-gonococcal urethritis. METHODS: The present study comprised 424 men with symptoms and signs compatible with acute urethritis. Their urethral swabs and first-voided urine underwent detection of the microorganisms. Demographic characteristics and clinical features of Mycoplasma genitalium-, Ureaplasma urealyticum-, Haemophilus influenza-, adenovirus- or Herpes simplex virus-positive monomicrobial non-gonococcal urethritis, or all-examined microorganism-negative urethritis in heterosexual men were compared with urethritis positive only for Chlamydia trachomatis. RESULTS: Neisseria gonorrhoeae was detected in 127 men (30.0%). In 297 men with non-gonococcal urethritis, C. trachomatis was detected in 143 (48.1%). In 154 men with non chlamydial non-gonococcal urethritis, M. genitalium (22.7%), M. hominis (5.8%), Ureaplasma parvum (9.1%), U. urealyticum (19.5%), H. influenzae (14.3%), Neisseria meningitidis (3.9%), Trichomonas vaginalis (1.3%), human adenovirus (16.2%), and Herpes simplex virus types 1 (7.1%) and 2 (2.6%) were detected. Although some features of monomicrobial non-chlamydial non-gonococcal urethritis or all-examined microorganism-negative urethritis were significantly different from those of monomicrobial chlamydial non-gonococcal urethritis, most features were superimposed. CONCLUSIONS: Predicting causative microorganisms in men with non-gonococcal urethritis based on demographic and clinical features is difficult. However, the present study provides useful information to better understand the microbiological diversity in non-gonococcal urethritis, and to manage patients with non-gonococcal urethritis appropriately. PMID- 26845625 TI - Mast cells and their activation in lung disease. AB - Mast cells and their activation contribute to lung health via innate and adaptive immune responses to respiratory pathogens. They are also involved in the normal response to tissue injury. However, mast cells are involved in disease processes characterized by inflammation and remodeling of tissue structure. In these diseases mast cells are often inappropriately and chronically activated. There is evidence for activation of mast cells contributing to the pathophysiology of asthma, pulmonary fibrosis, and pulmonary hypertension. They may also play a role in chronic obstructive pulmonary disease, acute respiratory distress syndrome, and lung cancer. The diverse mechanisms through which mast cells sense and interact with the external and internal microenvironment account for their role in these diseases. Newly discovered mechanisms of redistribution and interaction between mast cells, airway structural cells, and other inflammatory cells may offer novel therapeutic targets in these disease processes. PMID- 26845626 TI - Contribution of glutaredoxin-1 to S-glutathionylation of endothelial nitric oxide synthase for mesenteric nitric oxide generation in experimental necrotizing enterocolitis. AB - Endothelial nitric oxide synthase (eNOS) is critical for intestinal microcirculatory perfusion and therefore plays a key role in the development of necrotizing enterocolitis (NEC). eNOS-derived nitric oxide (NO) is inhibited by S glutathionylation of eNOS (eNOS-SSG), which can be reversed by glutaredoxin-1 (Grx1). Therefore, the objective of this study was to investigate the interplay between Grx1 and eNOS in regulating the following inflammation signal during the development of NEC. Primary mouse intestinal microvascular endothelial cells (MIMECs) and peritoneal macrophages were subjected to lipopolysaccharide treatment, and Grx1-/- mice were subjected to an NEC-inducing regimen of formula feeding in combination with hypoxia and hypothermia. The eNOS-SSG level and its activity were assessed using immunoprecipitated assay and NO production evaluation. NO-mediated Toll-like receptor 4 (TLR4) signaling and inflammation injury were further defined. NEC severity was significantly increased in Grx1-/- mice. Grx1-/- mice with NEC showed significantly decreased NO and increased O2*- production with increases in eNOS-SSG. Furthermore, TLR4 signaling, which is required for the development of NEC, was enhanced in the Grx1-deficient mice. These results suggest that eNOS-SSG within the MIMECs inhibited NO production and enhanced TLR4 activity, which were implicated in the pathogenesis of NEC. Grx1 deficiency increases the severity of NEC in association with eNOS-SSG. PMID- 26845627 TI - Effects of Hot Chemical Etching and 10-Metacryloxydecyl Dihydrogen Phosphate (MDP) Monomer on the Bond Strength of Zirconia Ceramics to Resin-Based Cements. AB - PURPOSE: The purpose of this in vitro study was to evaluate the hot chemical etching method on the shear bond strength between zirconia and two resin cements. MATERIALS AND METHODS: Sixty zirconia specimens (13 * 7.5 * 2.5 mm3 ) were prepared and treated as follows: (1) airborne-particle abrasion with 50 MUm Al2 O3 particles; (2) hot chemical etching for 10 minutes; (3) hot chemical etching for 30 minutes. Sixty composite cylinders of 3 mm diameter and height were prepared and bonded to zirconia specimens, which were divided into subgroups A and B. Group A: cemented with conventional resin cement (Variolink II); group B: cemented with 10-metacryloxydecyl dihydrogen phosphate (MDP) monomer containing resin cement (Panavia SA) after the application of surface treatments. Next, the specimens were stored in 37oC distilled water for 24 hours. Following water storage, shear bond strength test was performed at a 1 mm/min crosshead speed in a universal testing machine. The statistical analyses were performed with one-way ANOVA and post hoc Tukey tests. p < 0.05 was considered statistically significant. RESULTS: The results from all of the tested groups exhibited lower shear bond strength values than group II-B and higher shear bond strength values than group I-A (p < 0.05). CONCLUSION: The use of the hot chemical etching method for 10 minutes increased the shear bond strength of zirconia ceramics to both conventional and resin cements and seems to be an effective method. The MDP monomer-containing resin cement, Panavia SA, improved the resin bonding of zirconia ceramics when combined with airborne-particle abrasion. PMID- 26845628 TI - Adherence to the guidelines for adrenaline auto-injector prescription should be improved. PMID- 26845629 TI - Athletic Trainers' Beliefs About and Implementation of Evidence-Based Practice. AB - CONTEXT: Understanding the beliefs about and use of evidence-based practice (EBP) among athletic trainers (ATs) will help to determine appropriate strategies to improve implementation. OBJECTIVE: To examine the ATs' beliefs about and use of EBP. DESIGN: Cross-sectional study. SETTING: Online survey instrument. PATIENTS OR OTHER PARTICIPANTS: A total of 467 ATs responded to the survey request, a response rate of 11.67%. A total of 385 (9.6%) completed the EBP Beliefs Scale and 342 (8.5%) completed the EBP Implementation Scale. MAIN OUTCOME MEASURE(S): The EBP Beliefs Scale and EBP Implementation Scale were administered. The surveys collected demographic information in addition to information about participants' beliefs regarding EBP and implementation of EBP in clinical practice. RESULTS: The ATs demonstrated a level of neither agree nor disagree (56.00 +/- 7.86) on the EBP Beliefs Scale. Belief scores were higher among those ATs required to document for third-party reimbursement (P = .001), those with access to current research through professional journals other than the Journal of Athletic Training (P = .02), and those with a doctoral degree (P = .01). A low level of implementation (9.00 +/- 11.38), representing the implementation of EBP approximately 0 times in the previous 8 weeks, was found on the EBP Implementation Scale. Implementation scores were higher among preceptors (P = .01), those required to document for third-party reimbursement (P < .001), those with access to current research through professional journals (P = .002), and those with a doctoral degree (P = .01). CONCLUSIONS: Participants had a positive attitude toward EBP; however, they were not implementing EBP concepts when providing patient care. This suggests that additional information and EBP resources are needed so ATs can better implement EBP in practice. To provide the best patient care and to promote EBP within the profession, clinicians should make EBP a priority and advocate for EBP implementation. PMID- 26845630 TI - Direct and Indirect Costs Following Living Kidney Donation: Findings From the KDOC Study. AB - Some living kidney donors (LKDs) incur costs associated with donation, although these costs are not well characterized in the United States. We collected cost data in the 12 mo following donation from 182 LKDs participating in the multicenter prospective Kidney Donor Outcomes Cohort (KDOC) Study. Most LKDs (n = 167, 92%) had one direct cost or more following donation, including ground transportation (86%), health care (41%), meals (53%), medications (36%), lodging (23%), and air transportation (12%). LKDs missed 33 072 total work hours, 40% of which were unpaid and led to $302 175 in lost wages (mean $1660). Caregivers lost $68 655 in wages (mean $377). Although some donors received financial assistance, 89% had a net financial loss in the 12-mo period, with one-third (33%) reporting a loss exceeding $2500. Financial burden was higher for those with greater travel distance to the transplant center (Spearman's rho = 0.26, p < 0.001), lower household income (Spearman's rho = -0.25, p < 0.001), and more unpaid work hours missed (Spearman's rho = 0.52, p < 0.001). Achieving financial neutrality for LKDs must be an immediate priority for the transplant community, governmental agencies, insurance companies, nonprofit organizations, and society at large. PMID- 26845631 TI - Knowledge, Beliefs, Behaviors, and Social Norms Related to Use of Alternative Tobacco Products Among Undergraduate and Graduate Nursing Students in an Urban U.S. University Setting. AB - PURPOSE: The purpose of the study was to assess nursing students' knowledge, beliefs, behaviors, and social norms regarding use of alternative tobacco products (ATPs). DESIGN AND METHODS: This anonymous online survey was conducted with all students enrolled in a college of nursing. The survey utilized measures from several national tobacco studies to assess knowledge and beliefs about ATPs (hookahs, cigars or cigarillos, bidis, kreteks, smokeless tobacco, electronic cigarettes) compared to cigarettes, health effects of ATPs, personal use of ATPs, and social norms. Data were analyzed in SPSS 22.0 (SPSS Inc., Chicago, IL, USA). Descriptive statistics and frequencies were performed for basic sociodemographic data. Paired samples t tests were performed to determine differences for scaled measures. FINDINGS: Nursing students demonstrated very low levels of knowledge about ATPs and their health consequences, despite high rates of ATP personal use. About 76% of participants reported use of one or more ATPs once or more in their lifetimes. A greater proportion of students had used hookahs or waterpipes (39.6%) compared to cigarettes (32.7%). CONCLUSIONS: Nurses' lack of knowledge about the emerging use and health threats associated with ATPs may undermine their ability to provide appropriate tobacco cessation counseling. Research is needed to identify gaps in nurses' education regarding tobacco cessation counseling and to develop new counseling approaches specific to use of ATPs. CLINICAL RELEVANCE: Nurses play critical roles in counseling their patients for tobacco cessation. Further research and education about the risks presented by ATPs are critical to reducing excess tobacco-related mortality. PMID- 26845633 TI - Hypervalent Iodine as a Terminal Oxidant in Wacker-Type Oxidation of Terminal Olefins to Methyl Ketones. AB - A mimic of the Wacker process for C?O bond formation in terminal olefins can be initiated by a combination of the Pd(II) and hypervalent iodine reagent, Dess Martin periodinane to generate methyl ketones. This operationally simple and scalable method offers Markovnikov selectivity, has good functional group compatibility, and is mild and high yielding. PMID- 26845632 TI - Use of HPV testing for cervical screening in vaccinated women--Insights from the SHEVa (Scottish HPV Prevalence in Vaccinated Women) study. AB - The management of cervical disease is changing worldwide as a result of HPV vaccination and the increasing use of HPV testing for cervical screening. However, the impact of vaccination on the performance of HPV based screening strategies is unknown. The SHEVa (Scottish HPV Prevalence in Vaccinated women) projects are designed to gain insight into the impact of vaccination on the performance of clinically validated HPV assays. Samples collated from women attending for first cervical smear who had been vaccinated as part of a national "catch-up" programme were tested with three clinically validated HPV assays (2 DNA and 1 RNA). Overall HR-HPV and type specific positivity was assessed in total population and according to underlying cytology and compared to a demographically equivalent group of unvaccinated women. HPV prevalence was significantly lower in vaccinated women and was influenced by assay-type, reducing by 23-25% for the DNA based assays and 32% for the RNA assay (p = 0.0008). All assays showed over 75% reduction of HPV16 and/or 18 (p < 0.0001) whereas the prevalence of non 16/18 HR HPV was not significantly different in vaccinated vs unvaccinated women. In women with low grade abnormalities, the proportion associated with non 16/18 HR-HPV was significantly higher in vaccinated women (p < 0.0001). Clinically validated HPV assays are affected differentially when applied to vaccinated women, dependent on assay chemistry. The increased proportion of non HPV16/18 infections may have implications for clinical performance, consequently, longitudinal studies linking HPV status to disease outcomes in vaccinated women are warranted. PMID- 26845634 TI - Single-Cell Metabolite Profiling of Stalk and Glandular Cells of Intact Trichomes with Internal Electrode Capillary Pressure Probe Electrospray Ionization Mass Spectrometry. AB - In this report, we developed the pressure probe electrospray ionization-mass spectrometry with internal electrode capillary (IEC-PPESI-MS) which enables high spatial-resolution cell sampling, precise postsampling manipulation, and high detection sensitivity. Using this technique, a comparative in situ single-cell metabolite profiling of stalk and glandular cells, the two adjacent cell types comprising a trichome unit in tomato plants (Solanum lycopersicum L.), were performed to clarify the extent of metabolic differentiation between two cell types as well as among different types of trichomes. Owing to high sensitivity of the system, less than a picoliter cell sap from a single stalk cell sufficiently yielded a number of peaks of amino acids, organic acids, carbohydrates, and flavonoids. The minimal cell sap removal from a stalk cell without severe disturbance of trichome structure enabled sequential analysis of adjacent glandular cell on the same trichome, which showed the presence of striking differences in metabolite compositions between two adjacent cell types. Comparison among different types of trichome also revealed significant variations in metabolite profiles, particularly in flavonoids and acyl sugars compositions. Some metabolites were found only in specific cell types or particular trichome types. Although extensive metabolomics analysis of glandular cells of tomato trichomes has been previously documented, this is the first report describing cell-to-cell variations in metabolite compositions of stalk and glandular cells as well as in different trichome types. Further application of this technique may provide new insights into distinct metabolism in plant cells displaying variations in shape, size, function and physicochemical properties. PMID- 26845635 TI - Advancing family psychology. AB - To realize the broad and complex nature of the field of family psychology, I have slightly revised the mission statement of the Journal of Family Psychology (JFP) to capture contemporary scholarship in family psychology and to advance systems perspectives in this top-tier scientific journal. Over the next 6 years, I hope that authors will consider JFP as an outlet for their best work in the following areas: (1) JFP addresses societal challenges faced by families today; (2) JFP publishes important studies on what makes couple and family relationships work; (3) JFP is a leader in publishing reports that use cutting-edge sophisticated approaches to research design and data analysis; and (4) JFP imparts knowledge about effective therapy and prevention programs relevant to couples and families. The journal is also expanding its publication rate to eight issues per year. PMID- 26845636 TI - A Unified AMBER-Compatible Molecular Mechanics Force Field for Thiolate-Protected Gold Nanoclusters. AB - We present transferable AMBER-compatible force field parameters for thiolate protected gold nanoclusters. Five different sized clusters containing both organo soluble and water-soluble thiolate ligands served as test systems in MD simulations, and parameters were validated against DFT and experimental results. The cluster geometries remain intact during the MD simulations in various solvents, and structural fluctuations and energetics showed agreement with DFT calculations. Experimental diffusion coefficients and crystal structures were also reproduced with sufficient accuracy. The presented parameter set contains the minimum number of cluster-specific parameters enabling the use of these parameters for several different gold nanoclusters. The parameterization of ligands can also be extended to different types of ligands. PMID- 26845638 TI - 1,8-Naphthalimide-Based Planar Small Molecular Acceptor for Organic Solar Cells. AB - Four small molecular acceptors (SM1-4) comprising a central benzene core, two thiophene bridges and two 1,8-naphthalimide (NI) terminal groups were designed and synthesized by direct C-H activation. SM1 has a planar chemical structure and forms H-aggregation as films. By attachment of different substituents on the central benzene ring, the dihedral angles between the two NI end groups of SM1-4 gradually increased, leading to a gradual decrease of planarity. SM1-4 all possess a high-lying LUMO level, matching with wide band gap (WBG) polymer donors which usually have a high-lying LUMO level. When used in OSCs, devices based on SM1 and WBG donor PCDTBT-C12 gave higher electron mobility, superior film morphology and better photovoltaic performance. After optimization, a PCE of 2.78% with a V(oc) of 1.04 V was achieved for SM1 based devices, which is among the highest PCEs with a V(oc) higher than 1 V. Our results have demonstrated that NI based planar small molecules are potential acceptors for WBG polymer based OSCs. PMID- 26845637 TI - Histological spectrum of angiofibroma of soft tissue: histological and genetic analysis of 13 cases. AB - AIMS: Angiofibroma of soft tissue (AFST) is a rare soft tissue neoplasm characterized by a fibroblastic cytomorphology and a prominent vascular structure. AFSTs possess a novel fusion gene, i.e. NCOA2-AHRR/AHRR-NCOA2 or GTF2I NCOA2, providing a useful approach to diagnosing AFST. Morphologically, AFSTs span a wide spectrum, making diagnosis a challenge. The aim of this study was to review AFST cases and to report previously unknown histological features, which we confirmed by genetic analysis. METHODS AND RESULTS: We reviewed 276 cases diagnosed as solitary fibrous tumours/haemangiopericytomas (232 cases), unclassified tumours of fibroblastic differentiation (36 cases), and recently diagnosed AFSTs (eight cases), and retrieved 13 cases compatible with AFST. Immunohistochemical staining was performed for these cases, all 13 of which were analysed by reverse transcription polymerase chain reaction and fluorescence in situ hybridization. The histological findings were as follows: amianthoid fibres, extravasation of red blood cells, haemosiderin deposition, aggregates of foamy histiocytes, cystic change, necrosis, and haemorrhage. Immunohistochemically, the tumour cells were positive for epithelial membrane antigen (four of 13 cases), desmin (six of 13 cases), CD163 (13 of 13 cases), CD68 (seven of 13 cases), oestrogen receptor (13 of 13 cases), progesterone receptor (three of 13 cases), and STAT6 (one of 13 cases, weak nuclear staining), but they were negative for CD34, alpha-smooth muscle actin, muscle-specific actin, S100, pan-cytokeratin, MDM2, and CDK4. The AHRR-NCOA2 fusion gene was detected in eight cases, and NCOA2 gene rearrangement in nine cases. CONCLUSION: We revealed the previously unreported histological variation and immunohistochemical findings of AFST, and confirmed them by using genetic methods. The results suggested that AFST should be considered in the diagnosis of fibrous or fibrohistiocytic tumours with the above histological features. PMID- 26845639 TI - Synthesis and Characterization of [(OH)TeNb5O18](6-) in Water Solution, Comparison with [Nb6O19](8-). AB - Reaction of [Nb6O19](8-) with H6TeO6 in water gives telluropentaniobate [(OH)TeNb5O18](6-) (1) as single product, which was isolated as Na(+) and mixed Na(+)/K(+) salts. Crystal structures were determined for Na6[(OH)TeNb5O18].15H2O (Na6-1) and K6Na[Nb(5.5){Te(OH)}(0.5)O(18.5)].26H2O (K6Na-1). Formation of 1 was monitored with electrospray ionization mass spectrometry (ESI-MS) and (125)Te NMR techniques. Capillary electrophoresis was used to calculate electrophoretic mobilities and radii of the anionic species in solutions of [(OH)TeNb5O18](6-) and [Nb6O19](8-) in borate buffer. No condensation or degradation products were detected. Reactions of 1 with {Cp*Rh}(2+) sources gives 1:1 and 2:1 hybrid polyoxometalate, which are present in solution as a mixture of isomers, as detected by (125)Te NMR. The isomerism is related to various possibilities of coordination of {Cp*Rh}(2+) to different {M3O3} faces, relative to the unique Te atom. According to ESI-MS experiments in water and methanol, rapid redistribution of the organometallic fragments between the 1:1 and 2:1 complexes takes place. The 1:1 complexes are more stable in water, while 2:1 complexes dominate in methanol. X-ray structural analysis of the crystals isolated from 2:1 reaction mixture allowed identification of Na3[{Cp*Rh}2TeNb5O19].24H2O (Cp*2Rh2-1) with two {Cp*Rh}(2+) fragments capping the opposing faces of the Lindqvist anion. PMID- 26845640 TI - Reducing antibiotic prescriptions for respiratory tract infections in family practice: results of a cluster randomized controlled trial evaluating a multifaceted peer-group-based intervention. AB - Irrational antibiotic use for respiratory tract infections (RTI) is a major driver of bacterial resistance. The aim of this study was to evaluate the effect of a multifaceted peer-group based intervention aiming to reduce RTI-related antibiotic prescriptions in family practice. This was a cluster randomized controlled trial with pre- and follow-up measurement. The intervention was implemented through PharmacoTherapy Audit Meetings (PTAM) in which family physicians (FPs) and pharmacists collaborate. Four PTAM groups received the intervention consisting of: (1) FP communication skills training, including communication about delayed prescribing; (2) implementation of antibiotic prescribing agreements in FPs' Electronic Prescribing Systems; (3) quarterly feedback figures for FPs. Four other PTAM groups were matched controls. Primary outcome measure was the number of RTI-related antibiotic prescriptions after the intervention, assessed with multilevel linear regression analyses. Total number and number of prescriptions stratified by age (under/over 12 years) were analysed. At baseline, the average total number of RTI-related antibiotic prescriptions per 1,000 patients was 207.9 and 176.7 in the intervention and control PTAM groups, respectively. At follow-up, FPs in both the intervention and control groups prescribed significantly less antibiotics. For adolescents and adults, the drop in number of antibiotic prescription was significantly larger in the intervention groups (-27.8 per 1,000 patients) than the control groups (-7.2 per 1,000 patients; P<0.05). This multifaceted peer-group-based intervention was effective in reducing the number of RTI-related antibiotic prescriptions for adolescents and adults. To affect antibiotic prescribing in children other methods are needed. PMID- 26845641 TI - Programmably Shaped Carbon Nanostructure from Shape-Conserving Carbonization of DNA. AB - DNA nanostructures are versatile templates for low cost, high resolution nanofabrication. However, due to the limited chemical stability of pure DNA structures, their applications in nanofabrication have long been limited to low temperature processes or solution phase reactions. Here, we demonstrate the use of DNA nanostructure as a template for high temperature, solid-state chemistries. We show that programmably shaped carbon nanostructures can be obtained by a shape conserving carbonization of DNA nanostructures. The DNA nanostructures were first coated with a thin film of Al2O3 by atomic layer deposition (ALD), after which the DNA nanostructure was carbonized in low pressure H2 atmosphere at 800-1000 degrees C. Raman spectroscopy and atomic force microscopy (AFM) data showed that carbon nanostructures were produced and the shape of the DNA nanostructure was preserved. Conductive AFM measurement shows that the carbon nanostructures are electrically conductive. PMID- 26845642 TI - Reply. PMID- 26845643 TI - Correction to "2-(4,5,6,7-Tetrafluorobenzimidazol-2-yl)-4,4,5,5-tetramethyl-4,5 dihydro-1H-imidazole-3-oxide-1-oxyl, A Hydrogen-Bonded Organic Quasi-1D Ferromagnet". PMID- 26845644 TI - Gate-opening effect in ZIF-8: the first experimental proof using inelastic neutron scattering. AB - The gate-opening phenomenon in ZIFs is of paramount importance to understand their behavior in industrial molecular separations. Here we show for the first time using in situ inelastic neutron scattering (INS) the swinging of the -CH3 groups and the imidazolate linkers in the prototypical ZIF-8 and ZIF-8@AC hybrid materials upon exposure to mild N2 pressure. PMID- 26845646 TI - Announcement: Congenital Heart Defect Awareness Week--February 7-14, 2016. PMID- 26845645 TI - miR-450b-5p Suppresses Stemness and the Development of Chemoresistance by Targeting SOX2 in Colorectal Cancer. AB - To investigate the role of miR-450b-5p, a newly identified microRNA, located in the Xq26 region, in development of chemoresistance in colorectal cancer (CRC), and to explore the underlying mechanism by which miR-450b-5p regulates this process. In this study, we demonstrated that expression of miR-450b-5p was downregulated in recurrent CRC tissues. We found that expression of miR-450b-5p was significantly inhibited in response to 5-fluorouracil (5-FU) treatment in HT 29 cells and HCT-116 cells. Importantly, overexpression of miR-450b-5p in 5-FU resistant HT-29 cells reduced cell viability, but elevated DNA fragmentation levels and caspase-3 activity were induced by treatment with 5-FU. Conversely, inhibition of miR-450b-5p enhanced resistance to 5-FU, and promoted cell viability in HCT-116 cells. Mechanistically, we found that miR-450b-5p directly targeted SOX2, an essential factor in stem cells. Expression of miR-450b-5p was negatively correlated to the expression of SOX2, the percentages of CD133(+) cells present, and sphere-forming capacity in CRC cells. Finally, depletion of SOX2 abolished the effects of suppression of miR-450b-5p on stemness and chemoresistance in HT29 cells. We have demonstrated that miR-450b-5p inhibits stemness and development of chemoresistance to 5-FU in CRC cells. These results indicate that miR-450b-5p may be a key determinant of 5-FU sensitivity, and may represent a novel therapeutic target to facilitate chemotherapy for CRC. PMID- 26845647 TI - Pyroacm Resin: An Acetamidomethyl Derived Resin for Solid Phase Synthesis of Peptides through Side Chain Anchoring of C-Terminal Cysteine Residues. AB - The design, synthesis and utilization of an efficient acetamidomethyl derived resin for the peptide synthesis is presented using established Fmoc and Boc protocols via side chain anchoring. Cleavage of the target peptide from the resin is performed using carboxymethylsulfenyl chloride under mild conditions which gave in situ thiol-sulfenyl protection of the cysteine residues. The utility of the resin is successfully demonstrated through applications to the syntheses of model peptides and natural products Riparin 1.1 and Riparin 1.2. PMID- 26845649 TI - Nonsteroidal Anti-Inflammatory Drugs Cause Inhibition of the Growth Plate in Cultured Rat Metatarsal Bones: Retraction. AB - At the request of the authors, the Editors and Publisher retract the article "Nonsteroidal Anti-Inflammatory Drugs Cause Inhibition of the Growth Plate in Cultured Rat Metatarsal Bones" by Park et al, published ahead of print on July 2, 2015 in the Journal of Pediatric Orthopaedics. The corresponding author, Hyun Woo Kim, MD, has requested retraction of this report due to unresolvable issues regarding authorship. The veracity of the content has not been questioned. PMID- 26845651 TI - [Interventions compared: the pill and case report]. PMID- 26845648 TI - Protection against cardiac hypertrophy by geniposide involves the GLP-1 receptor / AMPKalpha signalling pathway. AB - BACKGROUND AND PURPOSE: Activation of glucagon-like peptide-1 (GLP-1) receptor exerts a range of cardioprotective effects. Geniposide is an agonist of GLP-1 receptor, but its role in cardiac hypertrophy remains completely unknown. Here, we have investigated its protective effects and clarified the underlying molecular mechanisms. EXPERIMENTAL APPROACH: The transverse aorta was constricted in C57/B6 mice and then geniposide was given orally for 7 weeks. Morphological changes, echocardiographic parameters, histological analyses and hypertrophic markers were used to evaluate hypertrophy. KEY RESULTS: Geniposide inhibited the hypertrophic response induced by constriction of the transverse aorta or by isoprenaline. Activation of 5'-AMP-activated protein kinase-alpha (AMPKalpha) and inhibition of mammalian target of rapamycin, ERK and endoplasmic reticulum stress were observed in hypertrophic hearts that were treated with geniposide. Furthermore, Compound C (CpC) or knock-down of AMPKalpha restricted protection of geniposide against cell hypertrophy and activation of mammalian target of rapamycin and ERK induced by hypertrophic stimuli. CpC or shAMPKalpha also abolished the protection of geniposide against endoplasmic reticulum stress induced by thapsigargin or dihtiothreitol. The cardio-protective effects of geniposide were ablated in mice subjected to CpC. GLP-1receptor blockade counteracted the anti-hypertrophic response and activation of AMPKalpha by geniposide. Knock-down of GLP-1 receptor also offset the inhibitory effects of geniposide on cardiac hypertrophy in vivo. CONCLUSIONS AND IMPLICATIONS: Geniposide protected against cardiac hypertrophy via activation of the GLP-1 receptor/AMPKalpha pathway. Geniposide is a potential therapeutic drug for cardiac hypertrophy. PMID- 26845650 TI - Cytological Diagnosis of T Lymphoblastic Leukemia/Lymphoma in Patients with Pleural Effusion as an Initial Clinical Presentation: Two Case Reports of an Algorithmic Approach Using Complete Immunohistochemical Phenotyping. AB - BACKGROUND: T cell lymphoblastic leukemia/lymphoma with the initial symptom of effusion is an uncommon condition. It may present a diagnostic challenge as lymphoblastic cells mimic normal lymphocytes under a low-power microscopic view. CASES: Two cases are presented, both male, with the first aged 31 years and the second aged 54 years. Both initially presented with chest pain and shortness of breath, and CT scans found an anterior mediastinal mass and left pleural effusion in both subjects. Cytological smears of pleural fluid in each case showed monotonous small-to-medium-sized lymphoid cells with moderate chromatin condensation and round-to-convoluted nuclei. There were prominent apoptotic bodies and mitosis in both cases. Immunohistochemistry of cell blocks demonstrated their T cell lineage and lymphoblastic nature. Diagnosis of T cell lymphoblastic leukemia/lymphoma was determined by a 3-step algorithmic approach using complete panels of immunohistochemical markers (CD3, CD20, Ki-67, CD10, CD5, CD99, CD1a, CD34, CD4, CD8, TDT, CD7, CD2 and CD68). CONCLUSION: An algorithmic approach based on cytological morphology and immunophenotyping is an effective way to diagnose T cell lymphoblastic leukemia/lymphoma in patients with an initial symptom of pleural effusion and insidious cytological morphology. PMID- 26845652 TI - [Development of a set of nursing-sensitive indicators for Swiss practice]. AB - BACKGROUND: The SwissDRG prospective payment system is known to inadequately account for nursing intensity due to the DRG group criteria insufficiently describing the variability of nursing intensity within individual diagnosis related groups. In order to allow for appropriate reimbursement and resource allocation, nursing intensity must be able to be explicitly quantified and accounted for. The aim of this project was to develop a set of nursing-sensitive indicators intended to reduce the variation within individual diagnosis-related groups, supplementary to existing SwissDRG group criteria. METHODS: The approach comprised a variety of methods. A systematic literature review, input from an advisory board and an expert panel, as well as three focus group interviews with nurses and nurse managers formed the basis for the synthesis of data and information gathered from these sources. RESULTS: A set of 14 nursing-sensitive indicators was developed. The indicators are intended to improve the homogeneity of nursing intensity within SwissDRG diagnosis-related groups. Before these nursing indicators can be adopted as group criteria, they must be formulated to conform with SwissDRG and tested empirically. CONCLUSION: This set of indicators can be seen at as a first step towards nursing intensity being adequately represented in SwissDRG diagnosis-related groups. The next challenge to be met is operationalising the indicators in codable form. PMID- 26845653 TI - [Mouthrinse in oral mucositis in the context of allogeneic stem cell transplantation: a qualitative study]. AB - BACKGROUND: Oral mucositis is a common side effect of allogeneic stem cell transplantation and can lead to increased morbidity, mortality and higher costs. It also has an impact on the quality of patients' lives. In the stem cell transplantation ward of a Swiss university hospital, patients are instructed according to current guidelines for mouthwash and their mouth status is evaluated daily. RESEARCH QUESTION: How do patients experience oral mucositis and what factors influence their behaviour to perform the mouth rinsing regularly? METHOD: In this qualitative part of a concurrent nested mixed methods research, 14 patients were interviewed using an interview guide. Data was analysed using content analysis methods. RESULTS: The results showed that, oral mucositis cannot be viewed separately from illness, isolation and care. The mucositis was only a heavy burden for patients with a severe occurrence. For patients with lower grade occurrences, other symptoms were more important. The research identified motivating and debilitating factors for a regular mouth rinsing, which is one of the most important preventive procedures. CONCLUSIONS: This study highlights how important it is to view oral mucositis in the context of the transplantation and that knowledge about motivating and hindering factors can support the nurses in caring for the patients. Improvement of patient self-management is a key aspect. PMID- 26845655 TI - [The construction of professional images of healthcare assistants and registered nurses]. AB - BACKGROUND: In the field of nursing in Switzerland, educations have experienced a fundamental reorganization with the implementation of the new law on Vocational and Professional Education and Training (2004). Among other things, this change affects professional images. PURPOSE: To show how the different professional images in the field of nursing are being constructed in the descriptions of professions by graduates after the reshaping of the educations and the occupational field in general. METHODS: In 110 semi-structured interviews, healthcare assistants and registered nurses (college diploma and Bachelor of Science) in their early careers were asked to explain their professional image. The participant's answers were analysed based on a qualitative content analysis and considering the theoretical background of Berger and Luckmann (1977). RESULTS: The interviews show that professional images emerge on the interaction of societal attributes and individual processes of adoption and revision. Graduates are challenged to adjust stereotypes and to achieve a balance between their own professional image and a missing or inappropriately perceived societal image. CONCLUSION: There should be further emphasis on the differentiation between the professions and the different educations in the field of nursing in order to achieve a better public perception of the different professions. PMID- 26845654 TI - [Nurses' Attitudes toward the "Advanced Nursing Process" before and after an educational intervention - a quasi-experimental study]. AB - BACKGROUND: The attitude of nurses influences their application of the Advanced Nursing Process. Studies reveal deficits in the application of the Advanced Nursing Process that is based on valid assessments and nursing classifications. These deficits affect decision-making and - as a result - nursing care quality. In German speaking countries nurses' attitudes towards nursing diagnoses as part of the Advanced Nursing Process were not yet measured. OBJECTIVE: The aim of this study was to evaluate the effects of an educational intervention on nurses' attitude. METHOD: A quasi-experimental intervention study was carried out in Austria and Germany. Before and after a standardised educational intervention 51 nurses estimated their attitude with the instrument Positions on Nursing Diagnosis (PND). Analyses were performed by Wilcoxon- and U-tests. RESULTS: Before the educational intervention the average attitude score of the Austrian nurses was more positive than in the German group. After the study intervention both groups regarded nursing diagnostics statistically significant more convincing and better understandable. However, both groups still described the application of the Advanced Nursing Process as difficult and demanding to perform. IMPLICATIONS: In the future, more attention should be given to the reflexion and development of nurses' attitude towards the Advanced Nursing Process because attitudes lead nurses' actions. In further studies influencing organizational and structural factors in diverse settings will be analysed. PMID- 26845656 TI - [Prioritizing research]. PMID- 26845661 TI - The challenge of embryonic mosaicism in preimplantation genetic screening. PMID- 26845662 TI - Laparoscopic Heller Myotomy for Non-Dilated Esophageal Achalasia in Children with Intraoperative Stepped Dilation Under Image Guidance: Attempting Complete Myotomy. AB - This study presents a modified surgical approach to laparoscopic myotomy for achalasia using stepped dilation with a Rigiflex balloon and contrast medium under image guidance. A 10-year-old boy with persistent dysphagia and vomiting had ingested only liquids for 3 months, losing >10 kg in body weight. Barium swallow and esophageal manometry diagnosed esophageal achalasia with mild esophageal dilatation. After failed pneumatic dilatation, laparoscopic Heller myotomy with Dor fundoplication was performed. Prior to surgery, a Rigiflex balloon dilator was placed within the esophagus near the diaphragmatic hiatus. A four-port technique was used, and mobilization of the esophagus was limited to the anterior aspect. A 5-cm Heller myotomy was performed, extending another 2 cm onto the anterior gastric wall. During myotomy, the Rigiflex balloon was serially dilated from 30 to 50 mL, and filled with contrast medium under fluoroscopic image guidance in order to maintain appropriate tension on the esophagus to facilitate myotomy, and to confirm adequate myotomy with sufficient release of lower esophageal sphincter by resecting residual circular muscle fibers. Residual circular muscle fibers can be simultaneously visualized under both fluoroscopic image guidance and direct observation through the laparoscope, and they were cut precisely until the residual notch fully disappeared. Dor fundoplication was completed. The operative time was 180 minutes, and oral intake was started after esophagography on postoperative day 1. As of the 12-month follow-up, the patient has not shown any symptoms, and his postoperative course appeared satisfactory. PMID- 26845663 TI - Reproduction numbers for epidemic models with households and other social structures II: Comparisons and implications for vaccination. AB - In this paper we consider epidemic models of directly transmissible SIR (susceptible -> infective -> recovered) and SEIR (with an additional latent class) infections in fully-susceptible populations with a social structure, consisting either of households or of households and workplaces. We review most reproduction numbers defined in the literature for these models, including the basic reproduction number R0 introduced in the companion paper of this, for which we provide a simpler, more elegant derivation. Extending previous work, we provide a complete overview of the inequalities among these reproduction numbers and resolve some open questions. Special focus is put on the exponential-growth associated reproduction number Rr, which is loosely defined as the estimate of R0 based on the observed exponential growth of an emerging epidemic obtained when the social structure is ignored. We show that for the vast majority of the models considered in the literature Rr >= R0 when R0 >= 1 and Rr <= R0 when R0 <= 1. We show that, in contrast to models without social structure, vaccination of a fraction 1-1/R0 of the population, chosen uniformly at random, with a perfect vaccine is usually insufficient to prevent large epidemics. In addition, we provide significantly sharper bounds than the existing ones for bracketing the critical vaccination coverage between two analytically tractable quantities, which we illustrate by means of extensive numerical examples. PMID- 26845664 TI - Adaptive evolution of foraging-related trait in intraguild predation system. AB - This paper considers a tri-trophic food chain in which the top predator (intraguild predator) also feeds on the basal resource. We refer to the model as intraguild predation. We analyze its dynamics from an evolutionary perspective. The attack rate or foraging effort of the middle species (intraguild prey) for the basal resources is assumed to be evolvable and is also assumed to be traded off with the vulnerability to being attacked by the top predator. We focus on the analysis of the evolutionary dynamics of the attack rate using the adaptive dynamics approximation of mutation limited evolution. In particular, the critical function analysis is applied. This study reveals that the evolutionary dynamics of the intraguild predation system is completely characterized by the concavity of the trade-off function and admits trichotomous dynamic scenarios: (1) when the trade-off function is more concave than the critical function, an evolutionary singular strategy exists and is a repeller; (2) when the trade-off function is less concave than the critical function, the evolutionary singular strategy is convergence stable and turns into an evolutionary branching point, in which case the monomorphic intraguild prey will split into two different types; (3) when the trade-off function is convex, the evolutionary singular strategy turns into a continuous stable strategy and is uninvadable. Our theoretical analysis suggests that the adaptive foraging behavior may strongly influence the community stability. Consequently, it may promote the diversity of intraguild prey and the persistence of the system on the evolutionary timescale, which highlight a more comprehensive mechanistic understanding of the intricate interplay between ecological and evolutionary force. This modeling approach provides a venue for research on indirect effects from an evolutionary perspective. PMID- 26845665 TI - Clinical Care Classification System Mobile-Friendly Web Tool. PMID- 26845666 TI - NI 2016 Geneva eHealth for all. PMID- 26845668 TI - Effect of body-weight suspension training versus treadmill training on gross motor abilities of children with spastic diplegic cerebral palsy. AB - BACKGROUND: Suspension training and treadmill training are commonly used for promoting functional gross motor skills in children with cerebral palsy. AIM: The aim of this study was to compare the effect of body-weight suspension training versus treadmill training on gross motor functional skills. DESIGN: Assessor blinded, randomized, controlled intervention study. SETTING: Outpatient rehabilitation facility. POPULATION: Twenty children with spastic diplegia (7 boys and 13 girls) in the age ranged from 6 to 8 years old were randomly allocated into two equal groups. All children were assessed at baseline, after 18 session and after 36-session. METHODS: During the twelve-week outpatient rehabilitation program, both groups received traditional therapeutic exercises. Additionally, one group received locomotor training using the treadmill while the other group received locomotor training using body-weight suspension through the dynamic spider cage. Assessment included dimensions "D" standing and "E" walking of the gross motor function measure, in addition to the 10-m Walking Test and the five times sit to stand test. Training was applied three times per week for twelve consecutive weeks. RESULTS: No significant difference was found in standing or walking ability for measurements taken at baseline or after 18 session of therapy. Measurements taken at 36-session showed that suspension training achieved significantly (P<0.05) higher average score than treadmill training for dimension D as well as for dimension E. No significant difference was found between suspension training and treadmill training regarding walking speed or sit to stand transitional skills. CONCLUSIONS: Body-weight suspension training is effective in improving walking and locomotor capabilities in children with spastic diplegia. After three month suspension training was superior to treadmill training. CLINICAL REHABILITATION IMPACT: Body-weight suspension training promotes adequate postural stability, good balance control, and less exertion which facilitates efficient and safe gait. PMID- 26845670 TI - Behavioral Pure-Tone Threshold Shifts Caused by Tympanic Membrane Electrodes. AB - OBJECTIVE: To determine whether tympanic membrane (TM) electrodes induce behavioral pure-tone threshold shifts. DESIGN: Pure-tone thresholds (250 to 8000 Hz) were measured twice in test (n = 18) and control (n = 10) groups. TM electrodes were placed between first and second threshold measurements in the test group, whereas the control group did not receive electrodes. Pure-tone threshold shifts were compared between groups. The effect of TM electrode contact location on threshold shifts was evaluated in the test group. RESULTS: TM electrodes significantly increased average low-frequency thresholds, 7.5 dB at 250 Hz and 4.2 dB at 500 Hz, and shifts were as large as 25 dB in individual ears. Also, threshold shifts did not appear to vary at any frequency with TM electrode contact location. CONCLUSIONS: Low-frequency threshold shifts occur when using TM electrodes and insert earphones. These findings are relevant to interpreting electrocochleographic responses to low-frequency stimuli. PMID- 26845671 TI - Polyoxovanadate-based organic-inorganic hybrids: from {V5O9Cl} clusters to nanosized octahedral cages. AB - Three polyoxovanadate-based metal-organic polyhedra (denoted as VMOP-1, -2, and 3), adopting isostructural discrete octahedral cage geometries, were successfully synthesized under solvothermal conditions. These structures are all built up from the same pentavanadate {V5O9Cl} cluster connected by linear bidentate ligands (H2L1 = H2BDC, H2L2 = H2BDC-NH2, H2L3 = H2BDC-Br), respectively. PMID- 26845672 TI - Immune activation and HIV: an enduring relationship. PMID- 26845673 TI - Immune activation in HIV infection: what can the natural hosts of simian immunodeficiency virus teach us? AB - PURPOSE OF REVIEW: The review summarizes studies in natural hosts, with a particular focus on the control of immune activation and new insights into viral reservoirs. We discuss why these findings are relevant for HIV research today. RECENT FINDINGS: AIDS resistance in natural hosts is characterized by a rapid control of inflammatory processes in response to simian immunodeficiency virus infection despite persistent viremia. Although CD4 T cells are dramatically depleted in the intestine in primary infection, interleukin 17-producing T helper cells (Th17) are preserved and natural hosts lack microbial translocation. Thus, viral replication in the gut is not sufficient to explain mucosal damage, but additional factors are necessary. Natural hosts also display a lower infection rate of stem-cell memory, central memory and follicular helper T cells. The follicles are characterized by a lack of viral trapping and the viral replication in secondary lymphoid organs is rapidly controlled. Hence, the healthy status of natural hosts is associated with preserved lymphoid environments. SUMMARY: Understanding the underlying mechanisms of preservation of Th17 and of the low contribution of stem-cell memory, central memory and follicular helper T cells to viral reservoirs could benefit the search for preventive and curative approaches of HIV. Altogether, the complementarity of the model helps to identify strategies aiming at restoring full capacity of the immune system and decreasing the size of the viral reservoirs. PMID- 26845675 TI - Immune activation and immune aging in HIV infection. AB - PURPOSE OF REVIEW: The development of serious non-AIDS-related pathologies typically associated with aging, and the premature immune aging that characterizes HIV-1-infected patients, even with suppressive antiretroviral therapy, have raised increasing concerns in recent years. Deciphering the causes of these phenomena is key for our understanding of HIV pathogenesis and for the clinical care of patients living with the virus. RECENT FINDINGS: An important basis for the immune parallels between HIV infection and aging lies in the exhaustion of the lymphopoietic capacity of infected individuals, which eventually affects all compartments of the immune system. The alleged cause for these immune alterations, and the onset of age-related comorbidities, is the systemic chronic immune activation that is established in patients. However, there is a multiplicity of contributors to this immune activation. SUMMARY: Our understanding of the precise link between immune activation and aging in HIV infection is complicated by the influence of coinfections and life style factors. Developing rational interventions to reduce the hyper-inflammatory status of HIV 1-infected patients requires a clearer delineation of the factors contributing to the increased levels of systemic immune activation. PMID- 26845674 TI - Sex differences in HIV-1-mediated immunopathology. AB - PURPOSE OF REVIEW: The article reviews our current knowledge regarding the role of sex and sex hormones in regulating innate immune responses to viral infections, which may account for the described sex differences in immunity to HIV-1. RECENT FINDINGS: Prominent sex differences exist in various infectious and autoimmune diseases. Biological mechanisms underlying these differences include the modulation of immunological pathways by sex hormones and gene dosage effects of immunomodulatory genes encoded by the X chromosome. During HIV-1 infections, women have been shown to present with lower viral load levels in primary infection, although their progression to AIDS is faster in comparison with men when accounting for viral load levels in chronic infection. HIV-1-infected women furthermore tend to have higher levels of immune activation and interferon stimulated gene expression in comparison with men for the same viral load, which has been associated to innate sensing of HIV-1 by Toll-like receptor 7 and the consequent interferon-alpha production by plasmacytoid dendritic cells. SUMMARY: Improvement in understanding the mechanisms associated with sex differences in HIV-1-mediated immunopathology will be critical to take sex differences into consideration when designing experimental and clinical studies in HIV-1-infected populations. PMID- 26845677 TI - Observational natural history and morphological taxonomy are indispensable for future challenges in biodiversity and conservation. AB - Global biodiversity is rapidly declining, leading inevitably to a loss of ecosystem functionality when species and their associated life-history traits vanish. Unfortunately, even in the 21(st) century, a large proportion of Earth's species are yet unknown and also for most described species science lacks a deeper understanding of the functional role of species and thus of ecosystems. In this Addendum we use the recent discovery of a new spider wasp with a unique natural history as an example to emphasize the importance to conduct basic observational natural history and traditional taxonomic research. We aim to encourage such 'old-fashioned' research and biologists from various research fields to report the many fascinating phenomena holding valuable natural history information they may encounter. Such detailed knowledge on species, their life history traits, and their trophic interactions will be crucial to reliably address the challenges global change brings to the persistence of ecosystems. PMID- 26845678 TI - MiR-15a contributes abnormal immune response in myasthenia gravis by targeting CXCL10. AB - MiR-15a is likely to be associated with autoimmunity. Here, we aimed to examine the expression of miR-15 cluster in PBMCs from myasthenia gravis (MG) patients and investigate the potential roles of miR-15a in MG. We found that the expression of all miR-15 cluster was decreased in MG, furthermore, miR-15a levels in ocular MG (oMG) were much lower, while CXCL10 production was increased in MG. We display that CXCL10 was a functional target gene of miR-15a in MG. Increasing miR-15a expression could reduce CXCL10 expression and alleviate the abnormal T cells activation in immune response, while decreasing miR-15a expression could activate immune response abnormally. Moreover, miR-15a expression was significantly decreased after stimulation, and prednisone treatment could upregulate miR-15a expression in steroid-responsive MG patients. Take together, our data suggest that decreased miR-15a expression facilitates proinflammatory cytokines production and contributes to immune response at least in part via regulating CXCL10 expression in MG. PMID- 26845679 TI - Free-Ranging Frigates (Fregata magnificens) of the Southeast Coast of Brazil Harbor Extraintestinal Pathogenic Escherichia coli Resistant to Antimicrobials. AB - Seabirds may be responsible for the spread of pathogenic/resistant organisms over great distances, playing a relevant role within the context of the One World, One Health concept. Diarrheagenic E. coli strains, known as STEC (shiga toxin producing E. coli), and the extraintestinal pathogenic E. coli (ExPEC and the subpathotype APEC), are among the E. coli pathotypes with zoonotic potential associated with the birds. In order to identify health threats carried by frigates and to evaluate the anthropic influence on the southern coast of Brazil, the aim of this work was to characterize E. coli isolated from free-ranging frigates in relation to virulence genotypes, serotypes, phylogenetic groups and antimicrobial resistance. Cloacal and choanal swabs were sampled from 38 Fregata magnificens from two oceanic islands and one rescue center. Forty-three E. coli strains were recovered from 33 out of the 38 birds (86.8%); 88.4% of strains showed some of the virulence genes (VGs) searched, 48.8% contained three or more VGs. None of the strains presented VGs related to EPEC/STEC. Some of the isolates showed virulence genotypes, phylogenetic groups and serotypes of classical human ExPEC or APEC (O2:H7, O1:H6, ONT:H7, O25:H4). Regarding antimicrobial susceptibility, 62.8% showed resistance, and 11.6% (5/43) were multidrug resistant. The E. coli present in the intestines of the frigates may reflect the environmental human impact on southeast coast of Brazil; they may also represent an unexplored threat for seabird species, especially considering the overlap of pathogenic potential and antimicrobial resistance present in these strains. PMID- 26845680 TI - Immunogenicity and Safety of Influenza Vaccination in Systemic Lupus Erythematosus Patients Compared with Healthy Controls: A Meta-Analysis. AB - OBJECTIVE: To assess the immunogenicity and safety of influenza vaccine in patients with systemic lupus erythematosus (SLE). METHODS: Relevant articles were retrieved from electronic databases. Seroprotection rate, seroconversion rate and factors that increase antibody geometric mean titer (GMT) were used as indices to measure the immunogenicity. The safety of vaccine was assessed through monitoring adverse events, which included side effects and SLE exacerbations. We performed a meta-analysis of influenza vaccine seroprotection, seroconversion and adverse effects. SLE exacerbation after vaccination was comprehensively described. We used the Committee for Proprietary Medicinal Products (CPMP) guidelines to determine whether influenza can induce adequate immunogenicity in patients with SLE. RESULTS: Eighteen studies with 1966 subjects met the inclusion criteria. At least 565 of the subjects were patients with low-to-moderate SLE Disease Activity Index (SLEDAI) score or stable SLE disease. Compared with the general population, seroprotection rate in SLE patients was significantly decreased in patients with H1N1 [odds ratio (OR) = 0.36, 95% confidence interval (CI): 0.27-0.50] and H3N2 vaccination (OR = 0.48, 95% CI: 0.24-0.93), but not influenza B vaccination (OR = 0.55, 95% CI: 0.24-1.25). Seroconversion rate also significantly decreased in patients with H1N1 (OR = 0.39, 95% CI: 0.27-0.57) and influenza B (OR = 0.47, 95% CI: 0.29-0.76) vaccination, but not H3N2 vaccination (OR = 0.62, 95% CI: 0.21 1.79). However, the immunogenicity of influenza vaccine in SLE patients almost reached that of the CPMP guidelines. The OR for side effects (patients versus healthy controls) was 3.24 (95% CI: 0.62-16.76). Among 1966 patients with SLE, 32 experienced mild exacerbation of SLE and five had serious side effects for other reasons. CONCLUSION: Influenza vaccine has moderate effect on protecting patients with SLE. The side effects of influenza vaccine are not serious and are manageable. With consideration of a higher risk of SLE exacerbation and a more severe course of infection among SLE patients, influenza vaccination should be promoted among SLE patients with a low-to-moderate SLEDAI score or stable disease. PMID- 26845682 TI - Do cell-autonomous and non-cell-autonomous effects drive the structure of tumor ecosystems? AB - By definition, a driver mutation confers a growth advantage to the cancer cell in which it occurs, while a passenger mutation does not: the former is usually considered as the engine of cancer progression, while the latter is not. Actually, the effects of a given mutation depend on the genetic background of the cell in which it appears, thus can differ in the subclones that form a tumor. In addition to cell-autonomous effects generated by the mutations, non-cell autonomous effects shape the phenotype of a cancer cell. Here, we review the evidence that a network of biological interactions between subclones drives cancer cell adaptation and amplifies intra-tumor heterogeneity. Integrating the role of mutations in tumor ecosystems generates innovative strategies targeting the tumor ecosystem's weaknesses to improve cancer treatment. PMID- 26845683 TI - Cellular senescence and tumor promotion: Is aging the key? AB - The senescence response is a potent tumor suppressor mechanism characterized by an irreversible growth arrest in response to potentially oncogenic signals to prevent the proliferation of damaged cells. Late in life, some of the features of senescent cells seem to mediate the development of age-related pathologies, including cancer. In the present review, we present a summary of the current knowledge regarding the causes, effector pathways and cellular features of senescence. We also discuss how the senescence response, initially a tumor suppressor mechanism, turns into a tumor promoter apparently as a consequence of aging. We argue that three age-related phenomena--senescence-associated secretory phenotype (SASP) dysregulation, decline in the immune system function and genomic instability--could contribute, independently or synergistically, to deteriorate the efficacy of the senescence response in stopping cancer. As a consequence, senescent cells could be considered premalignant cells, and targeting senescent cells could be a preventive and therapeutic strategy against cancer. PMID- 26845684 TI - Editorial: Cocaine and Cerebral Small Vessel: Is it a Negative Factor for Intravenous Thrombolysis? PMID- 26845685 TI - Editorial: Cardiovascular Disease Mortality Rates are Plateauing in Certain Age Groups and Regions. Can we Keep them Declining? PMID- 26845681 TI - Vibrio cholerae Biofilms and Cholera Pathogenesis. AB - Vibrio cholerae can switch between motile and biofilm lifestyles. The last decades have been marked by a remarkable increase in our knowledge of the structure, regulation, and function of biofilms formed under laboratory conditions. Evidence has grown suggesting that V. cholerae can form biofilm-like aggregates during infection that could play a critical role in pathogenesis and disease transmission. However, the structure and regulation of biofilms formed during infection, as well as their role in intestinal colonization and virulence, remains poorly understood. Here, we review (i) the evidence for biofilm formation during infection, (ii) the coordinate regulation of biofilm and virulence gene expression, and (iii) the host signals that favor V. cholerae transitions between alternative lifestyles during intestinal colonization, and (iv) we discuss a model for the role of V. cholerae biofilms in pathogenicity. PMID- 26845686 TI - Ruthenium porphyrin-induced photodamage in bladder cancer cells. AB - Photodynamic therapy (PDT) is a noninvasive treatment for solid malignant and flat tumors. Light activated sensitizers catalyze photochemical reactions that produce reactive oxygen species which can cause cancer cell death. In this work we investigated the photophysical properties of the photosensitizer ruthenium(II) porphyrin (RuP), along with its PDT efficiency onto rat bladder cancer cells (AY27). Optical spectroscopy verified that RuP is capable to activate singlet oxygen via blue and red absorption bands and inter system crossing (ISC) to the triplet state. In vitro experiments on AY27 indicated increased photo-toxicity of RuP (20MUM, 18h incubation) after cell illumination (at 435nm), as a function of blue light exposure. Cell survival fraction was significantly reduced to 14% after illumination of 20MUM RuP with 15.6J/cm(2), whereas the "dark toxicity" of 20MUM RuP was 17%. Structural and morphological changes of cells were observed, due to RuP accumulation, as well as light-dependent cell death was recorded by confocal microscopy. Flow cytometry verified that PDT-RuP (50MUM) triggered significant photo-induced cellular destruction with a photoxicity of (93%+/ 0.9%). Interestingly, the present investigation of RuP-PDT showed that the dominating mode of cell death is necrosis. RuP "dark toxicity" compared to the conventional chemotherapeutic drug cisplatin was higher, both evaluated by the MTT assay (24h). In conclusion, the present investigation shows that RuP with or without photoactivation induces cell death of bladder cancer cells. PMID- 26845688 TI - Attitudes towards Addressing Medical Absenteeism of Students: A Qualitative Study among Principals and Special Education Needs Coordinators in Dutch Secondary Schools. AB - BACKGROUND: Reducing school absenteeism benefits the health and educational opportunities of young people. The Dutch intervention Medical Advice for Sick reported Students (abbreviated as MASS) was developed to address school absenteeism due to sickness reporting, also called medical absenteeism. This study is part of a research project on the effectiveness of MASS and explores factors that influence the implementation and dissemination of the intervention, from schools' perspectives. The research questions include reasons schools have to implement MASS, their experiences in the implementation of MASS and their views on what is needed to ensure sustainable implementation. METHODS: A qualitative research method was used. Semi-structured interviews were held with nine principals and eight special education needs coordinators, working in nine secondary schools that apply MASS. Inductive content analysis was carried out. FINDINGS: The main reasons for schools to address medical absenteeism were their concerns about students' well-being and future prospects and their wish to share these concerns with students' parents. Participants also mentioned the wish to raise the threshold for reporting sick. According to the participants, MASS makes it easier for teachers to enter into conversation with students and their parents about medical absence. MASS prevents damage to the relationship with parents and medical problems being missed. In implementing MASS the main obstacles are teachers' dialogue about medical absence with students and their parents, teachers' follow-up of the feedback of the youth health care physicians (YHCPs), and correct registration. The participants were convinced that MASS also improves collaboration with parents regarding the optimization of care for students. CONCLUSIONS: MASS allows schools to identify students at risk of dropout at an early stage and to optimise guidance of these students. The intervention matches schools' need to address medical absenteeism by providing a clear framework, an approach from concern rather than control, and socio-medical expertise through the collaboration with YHCPs. MASS can support schools to maximize the number of students graduating and to improve parental involvement in school. These outcomes may help to put the subject of addressing medical absenteeism on the agenda of all schools, and contribute to prioritization, support adoption and secure sustainable implementation and dissemination of MASS. PMID- 26845689 TI - Two-stage autotransplantation of the human submandibular gland: First long-term results. AB - OBJECTIVES/HYPOTHESIS: Xerostomia is still one of the predominant side effects of radiotherapy (RT). This study investigates long-term results of a new surgical method that spares the submandibular gland from radiation. STUDY DESIGN: Eleven patients with head and neck carcinoma were enrolled in the study. In five patients 6-month follow-up testing, and in two of these patients 12-month follow up testing was performed. METHODS: The submandibular gland was transplanted to the patients forearm for the time of radiation. Two months after completion of RT, the gland was retransplanted to the neck. Patients saliva flow was tested via the Saxon test, and patients had to answer the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Head and Neck 35 and visual analog scale. RESULTS: Following the two-stage autotransplantation, xerostomia was reduced in the long term due to improved saliva production of the reimplanted gland. CONCLUSIONS: Whether this promising novel approach is a reliable treatment option for RT patients in general should be evaluated in further studies. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1551-1555, 2016. PMID- 26845687 TI - Erosion of Conserved Binding Sites in Personal Genomes Points to Medical Histories. AB - Although many human diseases have a genetic component involving many loci, the majority of studies are statistically underpowered to isolate the many contributing variants, raising the question of the existence of alternate processes to identify disease mutations. To address this question, we collect ancestral transcription factor binding sites disrupted by an individual's variants and then look for their most significant congregation next to a group of functionally related genes. Strikingly, when the method is applied to five different full human genomes, the top enriched function for each is invariably reflective of their very different medical histories. For example, our method implicates "abnormal cardiac output" for a patient with a longstanding family history of heart disease, "decreased circulating sodium level" for an individual with hypertension, and other biologically appealing links for medical histories spanning narcolepsy to axonal neuropathy. Our results suggest that erosion of gene regulation by mutation load significantly contributes to observed heritable phenotypes that manifest in the medical history. The test we developed exposes a hitherto hidden layer of personal variants that promise to shed new light on human disease penetrance, expressivity and the sensitivity with which we can detect them. PMID- 26845692 TI - Effects of problem-based learning in paediatric education in China: A meta analysis. AB - OBJECTIVE: To evaluate the efficiency of Problem-Based Learning (PBL) in paediatric education. METHODS: The research articles on the application of PBL to Chinese paediatric education published in from 1989 to 2014 in the Cochrane library, PubMed/MEDLINE, EBSCO (Elton B. Stephens Company Database), OVID (Ovid Technologies Database), Web of Science, CNKI (China National Knowledge Infrastructure Database), VIP (Wei Pu Database), WF (WanFang Database) and other databases were retrieved by two independent evaluators according to the inclusion and exclusion criteria. The heterogeneity of the retrieved data was analysed and a meta-analysis was performed using the RevMan 5.3 software. RESULTS: The articles were initially retrieved, and 11 randomized controlled trials (RCTs) were included for the meta-analysis. The PBL group was significantly superior to the Lecture-Based Learning (LBL) group for the paediatrics theoretical test score, case analysis score and overall student satisfaction, and the differences were statistically significant (P<0.05). CONCLUSIONS: PBL is superior to LBL method for Chinese paediatric education. This article is protected by copyright. All rights reserved. PMID- 26845690 TI - Genomic Modifiers of Natural Killer Cells, Immune Responsiveness and Lymphoid Tissue Remodeling Together Increase Host Resistance to Viral Infection. AB - The MHC class I D(k) molecule supplies vital host resistance during murine cytomegalovirus (MCMV) infection. Natural killer (NK) cells expressing the Ly49G2 inhibitory receptor, which specifically binds D(k), are required to control viral spread. The extent of D(k)-dependent host resistance, however, differs significantly amongst related strains of mice, C57L and MA/My. As a result, we predicted that relatively small-effect modifier genetic loci might together shape immune cell features, NK cell reactivity, and the host immune response to MCMV. A robust D(k)-dependent genetic effect, however, has so far hindered attempts to identify additional host resistance factors. Thus, we applied genomic mapping strategies and multicolor flow cytometric analysis of immune cells in naive and virus-infected hosts to identify genetic modifiers of the host immune response to MCMV. We discovered and validated many quantitative trait loci (QTL); these were mapped to at least 19 positions on 16 chromosomes. Intriguingly, one newly discovered non-MHC locus (Cmv5) controlled splenic NK cell accrual, secondary lymphoid organ structure, and lymphoid follicle development during MCMV infection. We infer that Cmv5 aids host resistance to MCMV infection by expanding NK cells needed to preserve and protect essential tissue structural elements, to enhance lymphoid remodeling and to increase viral clearance in spleen. PMID- 26845691 TI - A Development of Nucleic Chromatin Measurements as a New Prognostic Marker for Severe Chronic Heart Failure. AB - BACKGROUND: Accurate prediction of both mortality and morbidity is of significant importance, but it is challenging in patients with severe heart failure. It is especially difficult to detect the optimal time for implanting mechanical circulatory support devices in such patients. We aimed to analyze the morphometric ultrastructure of nuclear chromatin in cardiomyocytes by developing an original clinical histopathological method. Using this method, we developed a biomarker to predict poor outcome in patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: As a part of their diagnostic evaluation, 171 patients underwent endomyocardial biopsy (EMB). Of these, 63 patients diagnosed with DCM were included in this study. We used electron microscopic imaging of cardiomyocyte nuclei and an automated image analysis software program to assess whether it was possible to detect discontinuity of the nuclear periphery. Twelve months after EMB, all patients with a discontinuous nuclear periphery (Group A, n = 11) died from heart failure or underwent left ventricular assist device (VAD) implantation. In contrast, in patients with a continuous nuclear periphery (Group N, n = 52) only 7 patients (13%) underwent VAD implantation and there were no deaths (p<0.01). We then evaluated chromatin particle density (Nuc-CS) and chromatin thickness in the nuclear periphery (Per-CS) in Group N patients; these new parameters were able to identify patients with poor prognosis. CONCLUSIONS: We developed novel morphometric methods based on cardiomyocyte nuclear chromatin that may provide pivotal information for early prediction of poor prognosis in patients with DCM. PMID- 26845694 TI - Bootstrapping Q Methodology to Improve the Understanding of Human Perspectives. AB - Q is a semi-qualitative methodology to identify typologies of perspectives. It is appropriate to address questions concerning diverse viewpoints, plurality of discourses, or participation processes across disciplines. Perspectives are interpreted based on rankings of a set of statements. These rankings are analysed using multivariate data reduction techniques in order to find similarities between respondents. Discussing the analytical process and looking for progress in Q methodology is becoming increasingly relevant. While its use is growing in social, health and environmental studies, the analytical process has received little attention in the last decades and it has not benefited from recent statistical and computational advances. Specifically, the standard procedure provides overall and arguably simplistic variability measures for perspectives and none of these measures are associated to individual statements, on which the interpretation is based. This paper presents an innovative approach of bootstrapping Q to obtain additional and more detailed measures of variability, which helps researchers understand better their data and the perspectives therein. This approach provides measures of variability that are specific to each statement and perspective, and additional measures that indicate the degree of certainty with which each respondent relates to each perspective. This supplementary information may add or subtract strength to particular arguments used to describe the perspectives. We illustrate and show the usefulness of this approach with an empirical example. The paper provides full details for other researchers to implement the bootstrap in Q studies with any data collection design. PMID- 26845693 TI - Modification of Caffeic Acid with Pyrrolidine Enhances Antioxidant Ability by Activating AKT/HO-1 Pathway in Heart. AB - Overproduction of free radicals during ischemia/reperfusion (I/R) injury leads to an interest in using antioxidant therapy. Activating an endogenous antioxidant signaling pathway is more important due to the fact that the free radical scavenging behavior in vitro does not always correlate with a cytoprotection effect in vivo. Caffeic acid (CA), an antioxidant, is a major phenolic constituent in nature. Pyrrolidinyl caffeamide (PLCA), a derivative of CA, was compared with CA for their antioxidant and cytoprotective effects. Our results indicate that CA and PLCA exert the same ability to scavenge DPPH in vitro. In response to myocardial I/R stress, PLCA was shown to attenuate lipid peroxydation and troponin release more than CA. These responses were accompanied with a prominent elevation in AKT and HO-1 expression and a preservation of mnSOD expression and catalase activity. PLCA also improved cell viability and alleviated the intracellular ROS level more than CA in cardiomyocytes exposed to H2O2. When inhibiting the AKT or HO-1 pathways, PLCA lost its ability to recover mnSOD expression and catalase activity to counteract with oxidative stress, suggesting AKT/HO-1 pathway activation by PLCA plays an important role. In addition, inhibition of AKT signaling further abolished HO-1 activity, while inhibition of HO-1 signaling attenuated AKT expression, indicating cross-talk between the AKT and HO-1 pathways. These protective effects may contribute to the cardiac function improvement by PLCA. These findings provide new insight into therapeutic approaches using a modified natural compound against oxidative stress from myocardial injuries. PMID- 26845695 TI - The protective effect of lycopene on hypoxia/reoxygenation-induced endoplasmic reticulum stress in H9C2 cardiomyocytes. AB - Nowadays, drugs protecting ischemia/reperfusion (I/R) myocardium become more suitable for clinic. It has been confirmed lycopene has various protections, but lacking the observation of its effect on endoplasmic reticulum stress (ERS) mediated apoptosis caused by hypoxia/reoxygenation (H/R). This study aims to clarify the protective effect of lycopene on ERS induced by H/R in H9C2 cardiomyocytes. Detect the survival rate, lactic dehydrogenase (LDH) activity, apoptosis ratio, glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP), c-Jun-N-terminal protein Kinase (JNK) and Caspase-12 mRNA and protein expression and phosphorylation of JNK (p-JNK) protein expression. LDH activity, apoptosis ratio and GRP78 protein expression increase in the H/R group, reduced by lycopene. The survival rate reduces in the H/R and thapsigargin (TG) groups; lycopene and 4-phenyl butyric acid (4-PBA) can improve it caused by H/R, lycopene also can improve it caused by TG. The apoptosis ratio, the expression of GRP78, CHOP and Caspase-12 mRNA and protein and p-JNK protein increase in the H/R and TG groups, weaken in the lycopene+H/R, 4-PBA+H/R and lycopene+TG groups. There is no obvious change in the expression of JNK mRNA or protein. Hence, our results provide the evidence that 10 MUM lycopene plays an obviously protective effect on H/R H9C2 cardiomyocytes, realized through reducing ERS and apoptosis. The possible mechanism may be related to CHOP, p-JNK and Caspase-12 pathways. PMID- 26845696 TI - TGF-beta1 prevents rat retinal insult induced by amyloid-beta (1-42) oligomers. AB - To set up a retinal degenerative model in rat that mimics pathologic conditions such as age-related macular degeneration (AMD) using amyloid-beta (Abeta) oligomers, and assess the effect of TGF-beta1. Sprague-Dawley male rats were used. Human Abeta1-42 oligomers were intravitreally (ITV) injected (10uM) in the presence or in the absence of recombinant human TGF-beta1 (1ng/MUl ITV injected). After 48h, the animals were sacrificed and the eyes removed and dissected. The apoptotic markers Bax and Bcl-2 were assessed by western blot analysis in retina lysates. Gene-pathway network analysis was carried out in order to identify pathways involved in AMD. Treatment with Abeta oligomers induced a strong increase in Bax protein level (about 4-fold; p<0.01) and a significant reduction in Bcl-2 protein level (about 2-fold; p<0.05). Co-injection of TGF-beta1 triggered a significant reduction of Bax protein induced by Abeta oligomers. Bioinformatic analysis revealed that Bcl-2 and PI3K-Akt are the most connected nodes, for genes and pathways respectively, in the enriched gene-pathway network common to AMD and Alzheimer disease (AD). Overall, these data indicate that ITV injection of Abeta1-42 oligomers in rat induces molecular changes associated with apoptosis in rat retina, highlighting a potential pathogenetic role of Abeta oligomers in AMD. Bioinformatics analysis confirms that apoptosis pathways can take part in AMD. Furthermore, these findings suggest that human recombinant TGF beta1 can prevent retinal damage elicited by Abeta oligomers. PMID- 26845697 TI - Two hepcidins from spotted scat (Scatophagus argus) possess antibacterial and antiviral functions in vitro. AB - Hepcidins are small cysteine-rich antimicrobial peptides that play an important role in host immunity against pathogenic organisms. In this study, two hepcidins, SA-hepcidin1 and SA-hepcidin2, were cloned from spotted scat (Scatophagus argus), and the tissue distributions of SA-hepcidins were determined. In addition, mature SA-hepcidin peptides were synthesized to allow evaluation of their antimicrobial and antiviral functions in vitro. SA-hepcidin1 belongs to the HAMP1 class and is widely expressed in all tested tissues from spotted scat, whereas SA-hepcidin2 belongs to the HAMP2 class and present only in the liver. The synthetic SA hepcidins had similar levels of antibacterial activity against Gram-positive and Gram-negative bacteria; however, the antibacterial activity of SA-hepcidin1 was stronger than that of SA-hepcidin2. The antiviral activities of the synthetic SA hepcidins were assessed against Siniperca chuatsi rhabdovirus (SCRV) and largemouth bass Micropterus salmoides reovirus (MsReV) in epithelioma papulosum cyprini (EPC) and grass carp fin (GCF) cells. SA-hepcidin2 had antiviral activity, but SA-hepcidin1 did not. The results of this study suggest that SA hepcidins are important multifunctional proteins in the spotted scat immune system that are involved in resistance to various pathogens. PMID- 26845698 TI - Proteomic analysis by iTRAQ in red claw crayfish, Cherax quadricarinatus, hematopoietic tissue cells post white spot syndrome virus infection. AB - To elucidate proteomic changes of Hpt cells from red claw crayfish, Cherax quadricarinatus, we have carried out isobaric tags for relative and absolute quantitation (iTRAQ) of cellular proteins at both early (1 hpi) and late stage (12 hpi) post white spot syndrome virus (WSSV) infection. Protein database search revealed 594 protein hits by Mascot, in which 17 and 30 proteins were present as differentially expressed proteins at early and late viral infection, respectively. Generally, these differentially expressed proteins include: 1) the metabolic process related proteins in glycolysis and glucogenesis, DNA replication, nucleotide/amino acid/fatty acid metabolism and protein biosynthesis; 2) the signal transduction related proteins like small GTPases, G protein-alpha stimulatory subunit, proteins bearing PDZ- or 14-3-3-domains that help holding together and organize signaling complexes, casein kinase I and proteins of the MAP-kinase signal transduction pathway; 3) the immune defense related proteins such as alpha-2 macroglobulin, transglutaminase and trans activation response RNA-binding protein 1. Taken together, these protein information shed new light on the host cellular response against WSSV infection in a crustacean cell culture. PMID- 26845699 TI - Publication Rate of Abstracts Presented at the Annual Congress of the European Society for Surgical Research during 2008-2011. AB - BACKGROUND/PURPOSE: The presentation of scientific studies at major meetings serves to rapidly share study results with the scientific community. On the other hand, full-text publication of abstracts in peer-reviewed journals ensures the dissemination of science. This study examines the publication rate (PR) of meeting abstracts presented at the European Society for Surgical Research (ESSR) congresses and determines/compares the factors affecting the PRs. METHODS: All presentations at the ESSR congresses held during 2008-2011 were retrospectively assessed. Manuscripts indexed in PubMed were included. The meeting year, journal impact factor (IF) in the publication year, study type, presentation type, time to publication and geographic origin of studies were assessed. RESULTS: Among a total of 1,368 oral and poster abstracts, 48.7% (n = 391) of the oral presentations (OPs) and 29.7% (n = 168) of the poster presentations (PPs) were published in medical journals indexed in PubMed. The mean IF of the journals was 2.696 (0.17-14.95). The journals that published OPs had a higher IF than the journals in which PPs were published (2.944 vs. 2.118; p < 0.001). The PR was also higher in the OP group than in the PP group of journals (p < 0.001). The time to publication was 17.5 months (-166 to 82) and was shorter for PPs than for OPs (14.02 vs. 19.09 months; p = 0.01). According to the study type, experimental studies had a significantly higher PR (53.7%; p < 0.001); however, there was no significant difference in PR in terms of the prospective or retrospective nature of clinical studies. The clinical studies were also compared according to the IF values of the journals in terms of the prospective or retrospective nature of the study, and no significant difference was found (p = 0.62). CONCLUSION: The ESSR congress is an efficient meeting for researchers from varied surgical disciplines and has a PR equivalent to that of similar scientific meetings. The congress has achieved a PR of 40.9% over 4 years with an average IF of 2.696 and a mean time to publication of 17.5 months, which is equivalent to that of similar scientific meetings. OPs have a higher PR in journals with greater IF values as compared with PPs. PMID- 26845700 TI - A Feedback Loop between Inflammation and Zn Uptake. AB - OBJECTIVE: Zinc (Zn) has major effects on the immune system and inflammation is associated with systemic Zn deficiency. The aim of this work was to investigate how inflammation modifies Zn metabolism at the cellular level. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as a model of chronic inflammation. Osteoarthritis (OA) synoviocytes were used as control. METHODS: Zn levels were measured in medium and inside cells by Induced Coupled Plasma-Mass Spectrometry (ICP-MS), in the presence of minute quantities of stable spike 70Zn isotope and the addition or not of the pro-inflammatory cytokines interleukin-17 (IL-17) and tumor necrosis factor alpha (TNF-alpha). Gene expression of ZIP-8 importer, ZnT1 exporter and the homeostasis regulators metallothioneins (MTs) was evaluated after pre-exposure to cytokines, with or without exogenous Zn addition at increasing concentrations. IL-6 production was used as a marker of inflammation and measured by ELISA. RESULTS: Exposure to IL-17 and TNF-alpha enhanced expression of the Zn-importer ZIP-8, regardless of the concentration of Zn in the culture medium. In contrast, the expression of the Zn-exporter ZnT1 and of the MTs was primarily dependent on Zn levels. Addition of Zn also increased the production of IL-6, thus further stimulating the inflammatory response. CONCLUSION: IL-17/TNF-mediated inflammation enhanced the intracellular Zn uptake by synoviocytes, further increasing inflammation. These observations document the existence of a feedback loop between inflammation and Zn uptake. Based on these results, a mathematical model was developed to represent the cytokine-mediated Zn homeostasis alterations. PMID- 26845701 TI - Prevalence and Correlates of Elopement in a Nationally Representative Sample of Children with Developmental Disabilities in the United States. AB - Despite increased awareness and concern about children with developmental disabilities wandering away from adult supervision, there is a paucity of research about elopement. This is the first study to examine and report the prevalence and correlates of elopement in a nationally representative sample of school-age children in the United States with an autism spectrum disorder (ASD) and/or cognitive impairment. Data were obtained from the CDC's "Pathways" Survey, a follow-up telephone survey of the parents of 4,032 children with a developmental condition. 3,518 children that had ASD, intellectual disability (ID), and/or developmental delay (DD) at the time of survey administration were included for analysis. Children were divided into three condition groups: ASD only; ID/DD-only; ASD+ID/DD. Logistic regression analyses were used to compare the prevalence of elopement and rates of preventive measure use (barriers and/or electronic devices) across condition groups, and to examine the clinical and demographic correlates of elopement. T-tests were also performed to compare scores on the Children's Social Behavior Questionnaire (CSBQ) between wanderers and non-wanderers. Overall, 26.7% of children had reportedly eloped within the previous year, most commonly from public places. Children with ASD-only and ASD+ID/DD were more likely to have eloped than those with ID/DD-only. Across all groups, wanderers scored higher than non-wanderers on five out of six CSBQ subscales; they were more likely not to realize when there is danger, to have difficulty distinguishing between strangers and familiar people, to show sudden mood changes, to over-react to everything/everyone, to get angry quickly, to get lost easily, and to panic in new situations or if change occurs. Even after controlling for elopement history, parents of children in the ASD+ID/DD group were more likely than those in the other condition groups to report using physical or electronic measures to prevent wandering. PMID- 26845702 TI - Posterior Reversible Encephalopathy Syndrome Associated with Sorafenib and Successful Retreatment. AB - Posterior reversible encephalopathy syndrome (PRES) is a clinical and radiological syndrome characterized by acute hypertension, headache, decreased level of consciousness, visual disturbances and seizures associated with characteristic neuroimaging changes indicative of vasogenic edema of the posterior cerebral white matter. Several medical conditions have been associated with PRES including hypertensive encephalopathy and eclampsia. The use of cytotoxic and immunosuppressant drugs, such as those which target vascular endothelial growth factor (VEGF), have also been implicated. We report here the case of a 71-year-old woman with metastatic clear cell renal carcinoma who developed PRES 3 months after commencing sorafenib. Elevated blood pressure (BP) was recorded, and MRI of the brain) of the brain showed asymmetric areas of increased signal intensity within the supratentorial white matter suggestive of PRES. Clinical and radiological features rapidly improved with BP control and discontinuation of sorafenib. Sorafenib was resumed with no sign of PRES recurrence. The present case report supports the hypothesis that, in selected patients, the re-introduction of anti-VEGF therapies after PRES is feasible. PMID- 26845703 TI - Structure and gene cluster of the O-antigen of Escherichia coli O137. AB - The O-polysaccharide (O-antigen) was isolated from the lipopolysaccharide of Escherichia coli O137 and studied by sugar analysis and NMR spectroscopy. The following structure of the branched tetrasaccharide repeating unit was established: Formula: see text] Both structure and gene cluster of the E. coli O137 polysaccharide are related to those of the E. coli K40 polysaccharide (Amor et al., 1999), which lacks the side-chain glucosylation but contains serine that is amide-linked to GlcA. Functions of genes in the O137-antigen gene cluster were assigned by a comparison with those in K40 and sequences in the available databases. Particularly, predicted glycosyltransferases encoded in the gene cluster were assigned to the formation of three glycosidic linkages in the O polysaccharide repeating unit. PMID- 26845704 TI - Comparison of the simulations of cellulosic crystals with three carbohydrate force fields. AB - Three independently developed molecular mechanics force fields for carbohydrates have been used to simulate a suite of small molecule analogs of cellulose for which crystal structures have been reported, as a test to determine which might be best for simulations of cellulose itself. Such evaluation is necessary since the reported cellulose crystal structure is not stable in molecular dynamics simulations with any available force field. The present simulations found that all three resulted in small deviations from the reported crystal structures, but that all were reasonably accurate and none was clearly superior to the others for the entire suite of structures examined. PMID- 26845705 TI - Standardization of a Patella spp. (Mollusca, Gastropoda) embryo-larval bioassay and advantages of its use in marine ecotoxicology. AB - The use of three limpet species, Patella vulgata Linnaeus, 1758, Patella depressa Pennant, 1777 and Patella ulyssiponensis Gmelin, 1791 as model organisms in marine ecotoxicology has been evaluated. Initial laboratory experiments were aimed to standardize a biological test with embryos and larvae of Patella spp, establishing the percentage of normal trochophore larvae as endpoint. Before conducting in vitro fertilization, oocytes must be maturated artificially by incubation in an alkaline solution; therefore, alkalinizing agent, pH and time of eggs alkalinization were evaluated. Moreover, time of sperm activation, optimum sperm and oocytes concentration during fertilization, gamete contact time, use of stirring during the fertilization, egg concentration and incubation temperature were examined. Minimum sample size per treatment was also estimated. Exposure of oocytes for 10min to FSW alkalinized with NH4OH at pH 9.0, the use of undiluted sperm pre-activated during 45min and a concentration of 200 oocytesmL(-1), a gamete-contact time of 180min and egg incubation at 18 degrees C during 24h at a concentration of 80 eggsmL(-1) were the conditions allowing maximal embryo-larval development success. With an error of 0.05, a sampling size >=320 allows a 95% confidence in the estimate. This Patella spp. acute bioassay fulfills a number of important a priori requirements to be used in ecotoxicological studies. Nevertheless, in vitro fertilization requires considerable handling, which may lead to failure in fecundation. Such difficulties are also addressed, in order to facilitate the routine use of this protocol by other laboratories. PMID- 26845706 TI - Genetic Interaction between HOG1 and SLT2 Genes in Signalling the Cellular Stress Caused by Sulphuric Acid in Saccharomyces cerevisiae. AB - In fuel ethanol production, recycling of yeast biomass includes treatment of cells with diluted sulphuric acid in order to control bacterial population. However, this strategy might lead to a loss of cell viability, with potential negative consequences to the fermentation yield. In a recent paper we showed that the proteins Slt2 and Hog1 are essential for yeast tolerance to sulphuric acid. As a complement of the aforementioned work, we used DNA microarray technology to search for differentially expressed genes in hog1Delta and slt2Delta deletion mutants after treatment with sulphuric acid. Our results show how Slt2p and Hog1p could coordinate the interplay among protein kinase A (PKA), protein kinase C and high-osmolarity glycerol pathways. Moreover, the SSK22 and KDX1 genes may be part of this network, although their proteins were shown to be non-essential for cell growth/survival at low pH. These proteins might work by enhancing the signal which downregulates the PKA pathway leading to cell cycle arrest, in order to regenerate the integrity of yeast cell wall and cell homeostasis under acid shock. PMID- 26845708 TI - The Steroidal Glycoalkaloids from Solanaceae: Toxic Effect, Antitumour Activity and Mechanism of Action. AB - Steroidal glycoalkaloids present in Solanaceae are toxic compounds biosynthesised for the protection of the plants. However, many health benefits of these compounds have been reported so far. One of their promising targets might be cancer, as demonstrated in a large number of studies. However, the main mechanism of action seems to be unclear. It could include the induction of apoptosis or trigger a necrosis with a subsequent inflammatory response. The relatively high systemic toxicity of steroidal compounds is another effect that must be taken into account in anticancer research. The main aim of this work was to summarise the recent progress in the investigation of the mechanisms of their antitumour action and to discuss their potential. PMID- 26845707 TI - Comprehensive molecular testing in patients with high functioning autism spectrum disorder. AB - Autism spectrum disorders (ASD) include a range of complex neurodevelopmental disorders with extreme genetic heterogeneity. Exome and target sequencing studies have shown to be an effective tool for the discovery of new ASD genes. The aim of this study was to design an ASD candidate gene panel that covers 44 of the top ASD candidate genes. As a pilot study we performed comprehensive molecular diagnostic testing, including the study of the FMR1 and FMR2 repeat regions, copy number variant analysis in a collection of 50 Spanish ASD cases and mutation screening using targeted next generation sequencing-based techniques in 44 out of the total cohort. We evaluated and clinically selected our cohort, with most of the cases having high functioning ASD without facial dysmorphic features. The results of the present study allowed the detection of copy number and single nucleotide variants not yet identified. In addition, our results underscore the difficulty of the molecular diagnosis of ASD and confirm its genetic heterogeneity. The information gained from this and other genetic screenings is necessary to unravel the clinical interpretation of novel variants. PMID- 26845709 TI - A First Step in the Quest for the Active Constituents in Filipendula ulmaria (Meadowsweet): Comprehensive Phytochemical Identification by Liquid Chromatography Coupled to Quadrupole-Orbitrap Mass Spectrometry. AB - Filipendula ulmaria (meadowsweet) is traditionally used for the treatment of inflammatory diseases and as a diuretic and antirheumatic. Extracts of Filipendulae herba are on the market in the European Union as food supplements. Nevertheless, its active constituents remain to be revealed. During this study, the phytochemical composition of Filipendulae Ulmariae Herba was comprehensively characterised for the first time with two complementary generic ultrahigh performance liquid chromatography-photodiode array-accurate mass mass spectrometry methods. Selective ion fragmentation experiments with a hybrid quadrupole-orbital trap mass spectrometer significantly contributed to compound identification: a total of 119 compounds were tentatively identified, 69 new to F. ulmaria. A rich diversity of phenolic constituents was detected and only a few non-phenolic phytochemicals were observed. Metabolisation and pharmacological studies should be conducted to investigate which of these constituents or metabolites there of contribute to the activity of F. ulmaria after oral intake. PMID- 26845710 TI - Cratoxylum formosum Extract Protects against Amyloid-Beta Toxicity in a Caenorhabditis elegans Model of Alzheimer's Disease. AB - Amyloid-beta, one of the hallmarks of Alzheimer's disease, is toxic to neurons and causes cell death in the brain. Oxidative stress is known to play an important role in Alzheimer's disease, and there is strong evidence linking oxidative stress to amyloid-beta. The herbal plant "Tiew kon" (Cratoxylum formosum ssp. pruniflorum) is an indigenous vegetable that is grown in Southeast Asia. Many reports suggested that the twig extract from C. formosum possesses an antioxidant property. The purpose of this study was to investigate the protective effect of the twig extract from C. formosum against amyloid-beta toxicity using the transgenic Caenorhabditis elegans model. This study demonstrated that the extract significantly delayed amyloid-beta-induced paralysis in the C. elegans model of Alzheimer's disease. Using a genetic approach, we found that DAF-16/FOXO transcription factor, heat shock factor 1, and SKN-1 (Nrf2 in mammals) were required for the extract-mediated delayed paralysis. The extract ameliorated oxidative stress by reducing the level of H2O2, which appeared to account for the protective action of the extract. The extract possesses antioxidant activity against juglone-induced oxidative stress as it was shown to increase survival of the stressed worms. In addition, C. formosum decreased the expression of the heat shock protein-16.2 gene which was induced by thermal stress, indicating its ability to reduce cellular stress. The results from this study support the C. elegans model in the search for disease-modifying agents to treat Alzheimer's disease and indicate the potential of the extract from C. formosum ssp. pruniflorum as a source for the development of anti-Alzheimer's drugs. PMID- 26845711 TI - New Alkyl Phloroglucinol Derivatives from Rhus trichocarpa Roots and Their Cytotoxic Effects on Human Gastric Adenocarcinoma AGS Cells. AB - The phytochemical investigation of the roots of Rhus trichocarpa led to this isolation of five new alkyl phloroglucinol derivatives, characterized as (Z)-15 hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol A, 1), (Z)-15-hydroxy-1-(2,6-dihydroxy-4-methoxyphenyl)-9-octadecen-1-one (named trichocarpol B, 2), (Z)-17-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen-1-one (named trichocarpol C, 3), (Z)-18-hydroxy-1-(2,4,6-trihydroxyphenyl)-9-octadecen 1-one (named trichocarpol D, 4), and (9Z,12Z)-18-hydroxy-1-(2,4,6 trihydroxyphenyl)-9,12-octadecadien-1-one (named trichocarpol E, 5), together with a known compound, 4-(2,6-dihydroxy-4-methoxyphenyl)-4-oxobutanoic acid (6). In vitro cytotoxic activity of compounds 1-6 was evaluated in the human gastric adenocarcinoma AGS cell line and compounds 1-5 showed significant cytotoxicity. Our results indicate that R. trichocarpa, especially the alkyl phloroglucinol derivatives in it, is a good source of promising natural agents for the treatment of gastric cancer. PMID- 26845712 TI - Rosmarinic Acid--Pharmaceutical and Clinical Aspects. AB - The biosynthesis and biotechnological production of Rosmarinic acid, a phenolic ester that is widespread in the plant kingdom, has been widely investigated. This compound has shown many remarkable biological and pharmacological activities, which have led to its pharmaceutical and analytical development, as well as clinical studies, which are summarized and analyzed here for the first time. This review compiles data from the Pubmed, Scopus, Scifinder, Web Of Science, and Science Direct databases published between 1990 and 2015, restricting the search to works with the keywords "Rosmarinic acid" in the title. The initial search identified more than 800 articles; after an initial screening and removal of duplicate works, the search was further refined, resulting in approximately 300 articles that were scrutinized and comprise this review. The articles were organized to describe extraction and isolation, analytical methods, pharmaceutical development, and biological and pharmacological activities [divided into nonclinical (in vitro, in vivo) and clinical studies], pharmacokinetic studies, and stability studies. PMID- 26845713 TI - Development and verification of a mathematical model to quantify the joint spaces of the elbow. AB - The purpose of the study was a development and verification of a model to quantify elbow joint spaces focusing on posterolateral rotatory instability. The model was tested for feasibility and applied to open and arthroscopic surgeries. A mathematical kinematic model was created, consisting of two segments representing the humerus and radius and ulna. Model calculations of the joint opening were compared with direct measurements on a mechanical model with attached marker arrays, and compared with values determined by a digital sliding caliper in order to evaluate the mathematical kinematic rigid body model of the elbow joint. Joint angles predicted by the mathematical model were compared with values determined by a two axis goniometer. The evaluation showed significant accordance (intercorrelation coefficient >=0.8). The highest difference was 1.54 degrees (root mean square: 0.46 degrees ) for all movement conditions. Ligament transaction at the open surgery situation affected an increase in joint opening (maximum joint opening: 10.9 mm+/-0.3). Distances in the ulnohumeral joint space (ligaments intact) under arthroscopic surgery situation varied between 4.0 and 6.8 mm (mean: 5.2 mm+/-1.0). Thus a possibility is created to achieve an objective assessment of joint space opening to provide a more complete description of the elbow kinematics using this approach. PMID- 26845714 TI - Vertically transmitted cytomegalovirus infection in newborn preterm infants. AB - OBJECTIVE: To determine the epidemiology of congenital and acquired cytomegalovirus (CMV) infections in preterm infants and to analyze the efficacy of breast milk freezing in decreasing the vertical transmission rate of CMV. STUDY DESIGN: During 2013 and 2014, preterm newborns who weighed <=1500 g and were admitted to 22 Spanish neonatal units were included and screened for CMV infection according to the Spanish Neonatology Society recommendations. Each hospital treated the breast milk according to its own protocols. RESULTS: Among the 1236 preterm neonates included, 10 had a congenital infection (0.8%) and 49 had an acquired infection (4.0%) (82% demonstrated positive PCR-CMV in breast milk). The neonates who received only frozen milk presented less frequently with acquired infection (1.2%) than those fed fresh milk (5.5%) (RR=0.22; 95% CI 0.05 0.90; P=0.017). The newborns who received bank milk followed by frozen or fresh breast milk more frequently had an acquired infection (2.1% or 2.2%, respectively) than those fed only frozen breast milk. CONCLUSIONS: The incidence of congenital CMV infection in our sample is low, as described in the literature. To reduce acquired CMV infection, freezing breast milk might be an advisable procedure for preterm neonates born from seropositive mothers, either from the beginning of lactation or after a period of bank milk administration. PMID- 26845715 TI - Oral propranolol in early stages of retinopathy of prematurity. AB - OBJECTIVE: To assess the effect of oral propranolol on the progression of early stages of retinopathy of prematurity (ROP) in very low birth weight (VLBW) infants. METHODS: We analyzed VLBW infants with ROP (stages 2-3, zones II-III). Newborns received oral propranolol (0.5 mg/kg/dose q8h), and were monitored throughout the treatment period for possible side effects. Propranolol was administered until regression of ROP. A historic control group of patients with equivalent ROP was used. We compared characteristics of both groups and the progression of retinopathy. RESULTS: Forty-seven newborns were included, 20 in the propranolol group and 27 in the control group. There were no significant differences in gestational age, birthweight or gender. The mean duration of treatment with propranolol was 58.2+/-17.6 days. Most patients started treatment with stage 2 disease (65.0%), and had zone III involvement (55.0%). In the treated group, 90.0% (18/20) of patients did not require intervention with laser or bevacizumab, compared to 51.8% in the control group (P<0.005). No cases of bradycardia, hypotension or hypoglycemia were observed. CONCLUSIONS: Oral propranolol in early stages of ROP could prevent disease progression and reduce the need for invasive rescue therapy with laser or bevacizumab. No significant side effects were reported. PMID- 26845716 TI - Computerized vital signs analysis and late onset infections in extremely low gestational age infants. AB - AIM: Current clinical and laboratory diagnostics for neonatal infection are inadequate. An infant's systemic inflammatory response may be identified earlier than clinical suspicion by a computerized algorithm (RALIS) incorporating multiple vital signs (VS). We tested the ability of RALIS to detect late onset infection (LOI) earlier than clinically suspected. METHODS: We conducted a retrospective review of infants enrolled in a birth cohort study at Prentice Women's Hospital. VS data (heart rate, respirations, temperature, desaturation, bradycardia) were extracted from electronic records of 73 premature infants (born <=28 weeks' gestation; survived first month). RALIS generated a continuous output for the first 28 days of life. A score >=5 for 6 h triggered an alert. The time of RALIS alert to time of clinical suspicion of infection (time culture sent) was measured for each episode of suspected and/or confirmed LOI. RESULTS: Among the 73 infants followed with RALIS, there were 34 episodes of culture-positive LOI, seven culture-negative but treated episodes, and 13 false-positive culture (untreated) episodes. Twenty-five infants had no culture-positive or treated sepsis events during the observation period. There was a positive linear association between alert and culture (beta=0.88, P<0.001). Mean absolute time difference between alert and culture was 59.4 h before culture. Sensitivity and specificity of RALIS for LOI were 0.82 and 0.44. CONCLUSION: The RALIS algorithm is a sensitive indicator for early detection of infection in preterm infants. Further modifications to improve the specificity of the algorithm are needed prior to application of VS modeling to patient antibiotic treatment decisions. PMID- 26845717 TI - Antiproliferative effects of triterpenoidal derivatives, obtained from the marine sponge Siphonochalina sp., on human hepatic and colorectal cancer cells. AB - Three triterpenoidal derivatives [Sipholenol A (1), sipholenol L (2) and sipholenone A (3)] were isolated from the Red Sea sponge Siphonochalina sp. The structures were determined based on spectroscopic measurements (NMR, UV, IR and MS). The isolated compounds were evaluated for their cytotoxic activity against three cancer cell lines; HepG2, Caco-2 and HT-29. Moreover, the effects of these metabolites on cell cycle progression as well as cell cycle regulating proteins were assessed. Compounds 1, 2 and 3 showed moderate activity against HepG2 cells with IC(50) values of 17.18 +/- 1.18, 24.01 +/- 0.59 and 35.06 +/- 1.10 MUM, respectively. Compounds 1 and 2 exerted a considerable antiproliferative effect with IC(50) values of 4.80 +/- 0.18 and 26.64 +/- 0.30 MUM, respectively, against Caco-2 cells. Finally, 1 and 2 exhibited antiproliferative activity against colorectal cancer cells (HT-29) with IC(50) values of 24.65 +/- 0.80 and 4.48 +/- 0.1 MUM, respectively. Cell cycle analysis indicated that these compounds induced cell cycle arrest particularly in G0/G1 and S phases. Furthermore, the triterpenoids increased the expression of cyclin-B1, cyclin-D1 and cleaved caspase-3, as determined by immunofluorescence, indicating an important role of apoptosis in cell death induced by these compounds. PMID- 26845718 TI - Professor Peter Boger (23.03.1935 - 22.10.2015). PMID- 26845719 TI - Two new isoforms of the human hepatoma-derived growth factor interact with components of the cytoskeleton. AB - Hepatoma-derived growth factor (HDGF) is involved in diverse, apparently unrelated processes, such as cell proliferation, apoptosis, DNA-repair, transcriptional control, ribosome biogenesis and cell migration. Most of the interactions of HDGF with diverse molecules has been assigned to the hath region of HDGF. In this study we describe two previously unknown HDGF isoforms, HDGF-B and HDGF-C, generated via alternative splicing with structurally unrelated N terminal regions of their hath region, which is clearly different from the well described isoform, HDGF-A. In silico modeling revealed striking differences near the PHWP motif, an essential part of the binding site for glycosaminoglycans and DNA/RNA. This observation prompted the hypothesis that these isoforms would have distinct interaction patterns with correspondingly diverse roles on cellular processes. Indeed, we discovered specific associations of HDGF-B and HDGF-C with cytoskeleton elements, such as tubulin and dynein, suggesting previously unknown functions of HDGF in retrograde transport, site directed localization and/or cytoskeleton organization. In contrast, the main isoform HDGF-A does not interact directly with the cytoskeleton, but via RNA with messenger ribonucleoprotein (mRNP) complexes. In summary, the discovery of HDGF splice variants with their discrete binding activities and subcellular distributions opened new avenues for understanding its biological function and importance. PMID- 26845720 TI - Monitoring free light chains in serum using mass spectrometry. AB - BACKGROUND: Serum immunoglobulin free light chains (FLC) are secreted into circulation by plasma cells as a by-product of immunoglobulin production. In a healthy individual the population of FLC is polyclonal as no single cell is secreting more FLC than the total immunoglobulin secreting cell population. In a person with a plasma cell dyscrasia, such as multiple myeloma (MM) or light chain amyloidosis (AL), a clonal population of plasma cells secretes a monoclonal light chain at a concentration above the normal polyclonal background. METHODS: We recently showed that monoclonal immunoglobulin rapid accurate mass measurement (miRAMM) can be used to identify and quantify a monoclonal light chain (LC) in serum and urine above the polyclonal background. This was accomplished by reducing immunoglobulin disulfide bonds releasing the LC to be analyzed by microLC-ESI-Q-TOF mass spectrometry. Here we demonstrate that the methodology can also be applied to the detection and quantification of FLC by analyzing a non reduced sample. RESULTS: Proof of concept experiments were performed using purified FLC spiked into normal serum to assess linearity and precision. In addition, a cohort of 27 patients with AL was analyzed and miRAMM was able to detect a monoclonal FLC in 23 of the 27 patients that had abnormal FLC values by immunonephelometry. CONCLUSIONS: The high resolution and high mass measurement accuracy provided by the mass spectrometry based methodology eliminates the need for kappa/lambda ratios as the method can quantitatively monitor the abundance of the kappa and lambda polyclonal background at the same time it measures the monoclonal FLC. PMID- 26845721 TI - Validation of the "Vacutainer(r) urinalysis preservative plus urine tube" for the determination of albumin and protein. PMID- 26845722 TI - Quantitative nucleic acid amplification by digital PCR for clinical viral diagnostics. AB - In the past few years, interest in the development of digital PCR (dPCR) as a direct nucleic acid amplification technique for clinical viral diagnostics has grown. The main advantages of dPCR over qPCR include: quantification of nucleic acid concentrations without a calibration curve, comparable sensitivity, superior quantitative precision, greater resistance to perturbations by inhibitors, and increased robustness to the variability of the target sequence. In this review, we address the application of dPCR to viral nucleic acid quantification in clinical applications and for nucleic acid quantification standardization. Further development is required to overcome the current limitations of dPCR in order to realize its widespread use for viral load measurements in clinical diagnostic applications. PMID- 26845723 TI - Performance evaluation of a novel automated HIV Ag/Ab chemiluminescence immunoassay. PMID- 26845724 TI - Adipocytes in venipunctures cause falsely elevated S-100B serum values. PMID- 26845726 TI - Serum delipidation but not high-speed centrifugation is effective in clearing lipemia interference in serum lipase activity measurement. PMID- 26845725 TI - A relationship between absolute monocyte count and C-reactive protein in patients with migraine undergoing no pharmacological therapy. PMID- 26845727 TI - Macroprolactin: searching for a needle in a haystack? PMID- 26845728 TI - Preventive effect of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed obese rats. AB - BACKGROUND: The present study investigated the beneficial effects of curcumin on inflammation, oxidative stress and insulin resistance in high-fat fed male Wistar rats. METHODS: Five-month-old male Wistar rats (n=20) were divided into two groups (10 rats in each group). Among the two groups, one group received 30 % high-fat diet (HFD) and another group received 30 % HFD with curcumin (200 mg/kg body weight). Food intake, body weight and biochemical parameters were measured at the beginning and at the end of the study. After 10 weeks, oxidative stress parameters in skeletal muscle and hepatic triacylglycerol (TAG) content were estimated. Histological examinations of the liver samples were performed at the end of the experiment. RESULTS: High-fat feeding caused increase in body weight, liver and adipose tissue mass. Rats fed with HFD showed increased levels of fasting plasma glucose, insulin, Homeostasis Model Assessment for Insulin resistance (HOMA-IR), total cholesterol (TC), TAG, very low density lipoprotein cholesterol (VLDL-c) and decreased high-density lipoprotein cholesterol (HDL-c). There was also increase in the plasma inflammatory markers [tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP)] and skeletal muscle oxidative stress parameters [malondialdehyde (MDA), total oxidant status (TOS)] in these rats. In addition, high-fat feeding increased liver TAG content and caused fat accumulation in the liver. Treatment with curcumin significantly reduced body weight, relative organ weights (liver, adipose tissue), glucose, insulin and HOMA IR. Curcumin supplementation decreased plasma levels of TC, TAG, VLDL-c, TNF alpha and increased HDL-c. Administration of curcumin also reduced MDA, TOS in skeletal muscle, hepatic TAG content and liver fat deposition. CONCLUSIONS: Curcumin supplementation improved HFD-induced dyslipidemia, oxidative stress, inflammation and insulin resistance. PMID- 26845729 TI - Involvement of MTHFR and TPMT genes in susceptibility to childhood acute lymphoblastic leukemia (ALL) in Mexicans. AB - BACKGROUND: Folate metabolism plays an essential role in the processes of DNA synthesis and methylation. Deviations in the folate flux resulting from single nucleotide polymorphisms in genes encoding folate-dependent enzymes may affect the susceptibility to leukemia. This case-control study aimed to assess associations among MTHFR (C677T, A1298C) and TPMT (*2, *3A) mutations as well as to evaluate the synergistic effects of combined genotypes for both genes. Therefore, these genetic variants may lead to childhood acute lymphoblastic leukemia (ALL) susceptibility, in a Mexican population study. METHODS: DNA samples obtained from 70 children with ALL and 152 age-matched controls (range, 1 15 years) were analyzed by real-time reverse transcription polymerase chain reaction (RT-qPCR) to detect MTHFR C677T and A1298C and TPMT*2 and TPMT*3A genotypes. RESULTS: The frequency of the MTHFR A1298C CC genotype was statistically significant (odds ratio [OR], 6.48; 95% 95% confidence intervals [CI], 1.26-33.2; p=0.025). In addition, the combined 677CC+1298AC genotype exhibited a statistically significant result (OR, 0.23; 95% CI, 0.06-0.82; p=0.023). No significant results were obtained from the MTHFR (C677T CT, C677T TT) or TPMT (*2, *3A) genotypes. More importantly, no association between the synergistic effects of either gene (MTHFR and/or TPMT) and susceptibility to ALL was found. CONCLUSIONS: The MTHFR A1298C CC genotype was associated with an increased risk of developing childhood ALL. However, a decreased risk to ALL with the combination of MTHFR 677CC+1298AC genotypes was found. PMID- 26845730 TI - Endocrine and molecular investigations in a cohort of 25 adolescent males with prominent/persistent pubertal gynecomastia. AB - Pubertal gynecomastia is a common condition observed in up to 65% of adolescent males. It is usually idiopathic and tends to regress within 1-2 years. In this descriptive cross-sectional study, we investigated 25 adolescent males with prominent (>B3) and/or persistent (>2 years) pubertal gynecomastia (P/PPG) to determine whether a hormonal/genetic defect might underline this condition. Endocrine investigation revealed the absence of hormonal disturbance for 18 boys (72%). Three patients presented Klinefelter syndrome and three a partial androgen insensitivity syndrome (PAIS) as a result of p.Ala646Asp and p.Ala45Gly mutations of the androgen receptor gene. The last patient showed a 17alpha hydroxylase/17,20-lyase deficiency as a result of a compound heterozygous mutation of the CYP17A1 gene leading to p.Pro35Thr(P35T) and p.Arg239Stop(R239X) in the P450c17 protein. Enzymatic activity was analyzed: the mutant protein bearing the premature stop codon R239X showed a complete loss of 17alpha hydroxylase and 17,20-lyase activity. The mutant P35T seemed to retain 15-20% of 17alpha-hydroxylase and about 8-10% of 17,20-lyase activity. This work demonstrates that P/PPG had an endocrine/genetic cause in 28% of our cases. PAIS may be expressed only by isolated gynecomastia as well as by 17alpha hydroxylase/17,20-lyase deficiency. Isolated P/PPG is not always a 'physiological' condition and should thus be investigated through adequate endocrine and genetic investigations, even though larger studies are needed to better determine the real prevalence of genetic defects in such patients. PMID- 26845731 TI - The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults. AB - Bacterial meningitis and meningococcal sepsis are rare conditions with high case fatality rates. Early recognition and prompt treatment saves lives. In 1999 the British Infection Society produced a consensus statement for the management of immunocompetent adults with meningitis and meningococcal sepsis. Since 1999 there have been many changes. We therefore set out to produce revised guidelines which provide a standardised evidence-based approach to the management of acute community acquired meningitis and meningococcal sepsis in adults. A working party consisting of infectious diseases physicians, neurologists, acute physicians, intensivists, microbiologists, public health experts and patient group representatives was formed. Key questions were identified and the literature reviewed. All recommendations were graded and agreed upon by the working party. The guidelines, which for the first time include viral meningitis, are written in accordance with the AGREE 2 tool and recommendations graded according to the GRADE system. Main changes from the original statement include the indications for pre-hospital antibiotics, timing of the lumbar puncture and the indications for neuroimaging. The list of investigations has been updated and more emphasis is placed on molecular diagnosis. Approaches to both antibiotic and steroid therapy have been revised. Several recommendations have been given regarding the follow-up of patients. PMID- 26845732 TI - Partial body weight support treadmill training speed influences paretic and non paretic leg muscle activation, stride characteristics, and ratings of perceived exertion during acute stroke rehabilitation. AB - BACKGROUND: Intensive task-specific training is promoted as one approach for facilitating neural plastic brain changes and associated motor behavior gains following neurologic injury. Partial body weight support treadmill training (PBWSTT), is one task-specific approach frequently used to improve walking during the acute period of stroke recovery (<1month post infarct). However, only limited data have been published regarding the relationship between training parameters and physiologic demands during this early recovery phase. OBJECTIVE: To examine the impact of four walking speeds on stride characteristics, lower extremity muscle demands (both paretic and non-paretic), Borg ratings of perceived exertion (RPE), and blood pressure. DESIGN: A prospective, repeated measures design was used. METHODS: Ten inpatients post unilateral stroke participated. Following three familiarization sessions, participants engaged in PBWSTT at four predetermined speeds (0.5, 1.0, 1.5 and 2.0mph) while bilateral electromyographic and stride characteristic data were recorded. RPE was evaluated immediately following each trial. RESULTS: Stride length, cadence, and paretic single limb support increased with faster walking speeds (p?0.001), while non-paretic single limb support remained nearly constant. Faster walking resulted in greater peak and mean muscle activation in the paretic medial hamstrings, vastus lateralis and medial gastrocnemius, and non-paretic medial gastrocnemius (p?0.001). RPE also was greatest at the fastest compared to two slowest speeds (p<0.05). CONCLUSIONS: During the acute phase of stroke recovery, PBWSTT at the fastest speed (2.0mph) promoted practice of a more optimal gait pattern with greater intensity of effort as evidenced by the longer stride length, increased between-limb symmetry, greater muscle activation, and higher RPE compared to training at the slowest speeds. PMID- 26845734 TI - Remote-Controlled Release of Singlet Oxygen by the Plasmonic Heating of Endoperoxide-Modified Gold Nanorods: Towards a Paradigm Change in Photodynamic Therapy. AB - The photodynamic therapy of cancer is contingent upon the sustained generation of singlet oxygen in the tumor region. However, tumors of the most metastatic cancer types develop a region of severe hypoxia, which puts them beyond the reach of most therapeutic protocols. More troublesome, photodynamic action generates acute hypoxia as the process itself diminishes cellular oxygen reserves, which makes it a self-limiting method. Herein, we describe a new concept that could eventually lead to a change in the 100 year old paradigm of photodynamic therapy and potentially offer solutions to some of the lingering problems. When gold nanorods with tethered endoperoxides are irradiated at 808 nm, the endoperoxides undergo thermal cycloreversion, resulting in the generation of singlet oxygen. We demonstrate that the amount of singlet oxygen produced in this way is sufficient for triggering apoptosis in cell cultures. PMID- 26845733 TI - Induction of cytochromes P450 1A1 and 1A2 suppresses formation of DNA adducts by carcinogenic aristolochic acid I in rats in vivo. AB - Aristolochic acid I (AAI) is a natural plant alkaloid causing aristolochic acid nephropathy, Balkan endemic nephropathy and their associated urothelial malignancies. One of the most efficient enzymes reductively activating AAI to species forming AAI-DNA adducts is cytosolic NAD(P)H: quinone oxidoreductase 1. AAI is also either reductively activated or oxidatively detoxified to 8 hydroxyaristolochic acid (AAIa) by microsomal cytochrome P450 (CYP) 1A1 and 1A2. Here, we investigated which of these two opposing CYP1A1/2-catalyzed reactions prevails in AAI metabolism in vivo. The formation of AAI-DNA adducts was analyzed in liver, kidney and lung of rats treated with AAI, Sudan I, a potent inducer of CYP1A1/2, or AAI after pretreatment with Sudan I. Compared to rats treated with AAI alone, levels of AAI-DNA adducts determined by the (32)P-postlabeling method were lower in liver, kidney and lung of rats treated with AAI after Sudan I. The induction of CYP1A1/2 by Sudan I increased AAI detoxification to its O demethylated metabolite AAIa, thereby reducing the actual amount of AAI available for reductive activation. This subsequently resulted in lower AAI-DNA adduct levels in the rat in vivo. Our results demonstrate that CYP1A1/2-mediated oxidative detoxification of AAI is the predominant role of these enzymes in rats in vivo, thereby suppressing levels of AAI-DNA adducts. PMID- 26845735 TI - Dendritic cell function and antigen presentation in malaria. AB - Due to the diverse roles T cells play in protection against malaria as well as pathogenesis it is critical to know which cells present antigen and the nature of the antigens they present. During pre-erythrocytic stages of infection, cutting edge imaging studies have shown how Plasmodium antigens are presented during both the priming and effector phases of the protective CD8+ T cell response. During blood stages, pathology is in part due to the loss of DC function and the action of pathogenic T cells in the brain. Recently endothelial cells presenting malaria antigen to cognate T cells have emerged as critical players in malaria pathogenesis. Manipulating these processes may inform both vaccine design and the development of therapies for cerebral malaria. PMID- 26845736 TI - A novel liposome adjuvant DPC mediates Mycobacterium tuberculosis subunit vaccine well to induce cell-mediated immunity and high protective efficacy in mice. AB - Tuberculosis (TB) is a serious disease around the world, and protein based subunit vaccine is supposed to be a kind of promising novel vaccine against it. However, there is no effective adjuvant available in clinic to activate cell mediated immune responses which is required for TB subunit vaccine. Therefore, it is imperative to develop new adjuvant. Here we reported an adjuvant composed of dimethyl dioctadecylammonium (DDA), Poly I:C and cholesterol (DPC for short). DDA can form a kind of cationic liposome with the ability to deliver and present antigen and can induce Th1 type cell-mediated immune response. Poly I:C, a ligand of TLR3 receptor, could attenuate the pathologic reaction induced by following Mycobacterium tuberculosis challenge. Cholesterol, which could enhance rigidity of lipid bilayer, is added to DDA and Poly I:C to improve the stability of the adjuvant. The particle size and Zeta-potential of DPC were analyzed in vitro. Furthermore, DPC was mixed with a TB fusion protein ESAT6-Ag85B-MPT64(190-198) Mtb8.4-Rv2626c (LT70) to construct a subunit vaccine. The subunit vaccine-induced immune responses and protective efficacy against M. tuberculosis H37Rv infection in C57BL/6 mice were investigated. The results showed that the DPC adjuvant with particle size of 400 nm and zeta potential of 40 mV was in good stability. LT70 in the adjuvant of DPC generated strong antigen-specific humoral and cell mediated immunity, and induced long-term higher protective efficacy against M. tuberculosis infection (5.41 +/- 0.38log10CFU) than traditional vaccine Bacillus Calmette-Guerin (BCG) (6.01 +/- 0.33log10CFU) and PBS control (6.53 +/- 0.26log10CFU) at 30 weeks post-vaccination. In conclusion, DPC would be a promising vaccine adjuvant with the ability to stimulate Th1 type cell-mediated immunity, and could be used in TB subunit vaccine. PMID- 26845737 TI - The potential role of 13-valent pneumococcal conjugate vaccine in preventing respiratory complications in bacteraemic pneumococcal community-acquired pneumonia. AB - INTRODUCTION: Pneumococcal 13-valent vaccine (PCV-13) has a potential role in preventing bacteraemic pneumococcal pneumonia and its complications, but little is known about its ability to specifically prevent respiratory complications. Our aim were to analyse the pneumococcal serotypes associated with the development of respiratory complications and the potential role of PCV-13 in preventing respiratory complications in bacteraemic pneumococcal pneumonia. MATERIAL AND METHODS: We analysed demographic characteristics, comorbidities, antibiotic resistances and the outcomes of a cohort of 65 vaccine-naive bacteraemic pneumococcal pneumonias, stratified by the pneumococcal serotypes included in PCV13 vs. those not included. Complications were clustered as follows: respiratory complications (hypoxemic respiratory failure; mechanical ventilation), systemic complications (septic shock; multiorgan failure), suppurative complications (empyema; pleural effusion; lung abscess). RESULTS: From a population of 65 CAP-SP, 47.7% of the isolates belonged to PCV-13 serotypes group. No differences in comorbidities or clinical manifestations were found between groups. With regard to biochemical parameters, we found more profound hypoxemia levels in PCV-13 serotypes group comparing to non-vaccine group [PaO2/FiO2 209 (63) vs. 268 (57); p=0.007]. Global complications were identified in 69.2% (45 patients), and the most frequent were respiratory complications, found in 47.7%. Respiratory complications were detected more frequently in PCV-13 groups compared to non-vaccine groups (61.3% vs. 35.3%; p=0.036). Overall 30-day mortality was 30.8%. Mortality was similar between both groups (25.8% vs. 35.3%; p=0.408). CONCLUSIONS: Pneumococcal 13-valent conjugate vaccine includes the serotypes which cause more respiratory complications in our series; these serotypes were not associated with higher mortality in our series. PCV-13 may have a potential role in preventing respiratory complications due to bacteraemic pneumonoccal pneumonia. PMID- 26845738 TI - Evaluation of the non-toxic mutant of the diphtheria toxin K51E/E148K as carrier protein for meningococcal vaccines. AB - Diphtheria toxin mutant CRM197 is a common carrier protein for glycoconjugate vaccines, which has been proven an effective protein vector for, among others, meningococcal carbohydrates. The wide-range use of this protein in massive vaccine production requires constant increase of production yields and adaptability to an ever-growing market. Here we compare CRM197 with the alternative diphtheria non-toxic variant DT-K51E/E148K, an inactive mutant that can be produced in the periplasm of Escherichia coli. Biophysical characterization of DT-K51E/E148K suggested high similarity with CRM197, with main differences in their alpha-helical content, and a suitable purity for conjugation and vaccine preparation. Meningococcal serogroup A (MenA) glycoconjugates were synthesized using CRM197 and DT-K51E/E148K as carrier proteins, obtaining the same conjugation yields and comparable biophysical profiles. Mice were then immunized with these CRM197 and DT-K51E/E148K conjugates, and essentially identical immunogenic and protective effects were observed. Overall, our data indicate that DT-K51E/E148K is a readily produced protein that now allows the added flexibility of E. coli production in vaccine development and that can be effectively used as protein carrier for a meningococcal conjugate vaccine. PMID- 26845740 TI - Knowledge, attitude and awareness among healthcare professionals about influenza vaccination in Peshawar, Pakistan. AB - A cross-sectional study was carried out among HCPs in Northwest General Hospital & Research Centre, Hayatabad Peshawar, Pakistan. The purpose of this study was to investigate knowledge, awareness and attitude of HCPs towards influenza vaccination. A total of N=170 questionnaires were distributed among the staff. There was a 97% response rate to this survey (n=165). The median age of the respondents was 30 years and most of them, 98 (59.0%), were from age group of 24 30 years. The majority of the HCPs that participated in this study were male 106 (64.2%), and by profession, the majority were physicians 77 (46.7%), followed by pharmacists and nurses. A majority 114 (69.1%) believed that it was not compulsory for HCPs to get vaccinated for influenza. Top three identified barriers to vaccination were: not everyone is familiar with the availability of the influenza vaccination at their institution (Relative importance weight factors (RIWF)=0.71), due to needle fear I do not like to get vaccinated (RIWF=0.70) and it is not compulsory for healthcare professionals to get vaccinated for influenza (RIWF=0.64). The logistic regression analysis has revealed association for job experience and profession with the most of the eleven knowledge item. However, when overall sum of eleven items were tested to identify the factors affecting the knowledge score, along with profession (-0.215 [-0.389 to 0.040]; p=0.016) and job experience (0.823 [0.521-1.125]; p<0.001) HCPs age (-0.409 [-0.755 to -0.064]; p=0.020) was found to be another significant factor affecting the total knowledge score of HCPs. Overall, scoring of the correct responses revealed that nurses have better knowledge and understanding about influenza and the influenza vaccination (6.5 +/- 0.8, p<0.001*), followed by pharmacists (6.3 +/- 1.14) and physicians. In spite of the published guidelines and recommendations, a very low percentage of the healthcare professionals in our hospital were vaccinated against influenza, and the barriers to vaccination were prevalent. Various strategies, including arranging seminars regarding awareness about vaccinations, are required to improve the knowledge and overall outcomes. PMID- 26845739 TI - A phase 3, randomized, active-controlled study to assess the safety and tolerability of meningococcal serogroup B vaccine bivalent rLP2086 in healthy adolescents and young adults. AB - BACKGROUND: Neisseria meningitidis serogroup B (MnB) is an important cause of invasive meningococcal disease (IMD). A MnB vaccine (bivalent rLP2086, Trumenba((r))) consisting of 2 factor H binding protein variants received accelerated approval in the United States for the prevention of IMD caused by MnB in individuals 10-25 years of age. This randomized, active-controlled, observer blind study further assessed the safety and tolerability of bivalent rLP2086. METHODS: Eligible subjects >= 10 to < 26 years were randomized (2:1) to receive bivalent rLP2086 at months 0, 2, and 6, or hepatitis A virus vaccine (HAV, Havrix((r))) at months 0 and 6, and saline at month 2. The primary endpoints were serious adverse events (SAEs) throughout the study and medically-attended adverse events (MAEs) within 30 days after vaccination. Additional safety assessments included SAEs at other study intervals and adverse events (AEs) during the vaccination phase. RESULTS: Of 5712 subjects randomized, 84.6% (n = 3219) of bivalent rLP2086 recipients and 87.2% (n = 1663) of HAV/saline recipients completed the study. Throughout the study, SAEs were reported for 1.6% and 2.5% of bivalent rLP2086 and HAV/saline recipients, respectively. SAEs related to either vaccine were rare. MAEs occurred in 7.0% and 6.1% of subjects after vaccination 1; 5.5% and 6.1% after vaccination 2; and 5.3% and 5.5% after vaccination 3 in the bivalent rLP2086 and HAV/saline groups, respectively. A greater proportion of subjects reported AEs during the vaccination phase after bivalent rLP2086 compared with HAV/saline recipients; however, when reactogenicity events were excluded, the proportion between groups was similar. CONCLUSION: This safety study, the largest randomized, active-controlled trial evaluating a recombinant MnB vaccine, demonstrated that bivalent rLP2086 is safe and tolerable in healthy individuals >= 10 to < 26 years of age. PMID- 26845741 TI - High-throughput characterization of virus-like particles by interlaced size exclusion chromatography. AB - The development and manufacturing of safe and effective vaccines relies essentially on the availability of robust and precise analytical techniques. Virus-like particles (VLPs) have emerged as an important and valuable class of vaccines for the containment of infectious diseases. VLPs are produced by recombinant protein expression followed by purification procedures to minimize the levels of process- and product-related impurities. The control of these impurities is necessary during process development and manufacturing. Especially monitoring of the VLP size distribution is important for the characterization of the final vaccine product. Currently used methods require long analysis times and tailor-made assays. In this work, we present a size-exclusion ultra-high performance liquid chromatography (SE-UHPLC) method to characterize VLPs and quantify aggregates within 3.1min per sample applying interlaced injections. Four analytical SEC columns were evaluated for the analysis of human B19 parvo-VLPs and murine polyoma-VLPs. The optimized method was successfully used for the characterization of five recombinant protein-based VLPs including human papillomavirus (HPV) VLPs, human enterovirus 71 (EV71) VLPs, and chimeric hepatitis B core antigen (HBcAg) VLPs pointing out the generic applicability of the assay. Measurements were supported by transmission electron microscopy and dynamic light scattering. It was demonstrated that the iSE-UHPLC method provides a rapid, precise and robust tool for the characterization of VLPs. Two case studies on purification tools for VLP aggregates and storage conditions of HPV VLPs highlight the relevance of the analytical method for high-throughput process development and process monitoring of virus-like particles. PMID- 26845742 TI - Comparison of the PRNT and an immune fluorescence assay in yellow fever vaccinees receiving immunosuppressive medication. AB - BACKGROUND: The 17D-yellow fever (YF) vaccination is considered contraindicated in immune-compromised patients; however, accidental vaccination occurs. In this population, measuring the immune response is useful in clinical practice. METHODS: In this study we compare two antibody tests (the Immune Fluorescence Assay and the Plaque Reduction Neutralization Test) in a group of Dutch immune compromised travellers with a median of 33 days (IQR [28-49]) after primary YF vaccination. RESULTS: We collected samples of 15 immune-compromised vaccinees vaccinated with the 17D yellow fever vaccine between 2004 and 2012. All samples measured in the plaque reduction neutralization test yielded positive results (>80% virus neutralization with a 1:10 serum dilution). Immune Fluorescence Assay sensitivity was 28% (95% CI [0.12-0.49]). No adverse events were reported. CONCLUSIONS: All immune-compromised patients mounted an adequate response with protective levels of virus neutralizing antibodies to the 17-D YF vaccine. No adverse effects were reported. Compared to the plaque reduction neutralization test, the sensitivity of the Immune Fluorescence Assay test was low. Further research is needed to ascertain that 17D vaccination in immune-compromised patients is safe. PMID- 26845743 TI - There is no hierarchy in the first place-a comment on Jurgen Windeler. PMID- 26845744 TI - A new classification of spin in systematic reviews and meta-analyses was developed and ranked according to the severity. AB - OBJECTIVES: We aimed to (1) identify and classify spin (i.e., a description that overstates efficacy and/or understates harm) in systematic reviews and (2) rank spin in abstracts of systematic reviews according to their severity (i.e., the likelihood of distorting readers' interpretation of the results). STUDY DESIGN: First, we used a four-phase consensus process to develop a classification of different types of spin. Second, we ranked the types of spin in abstracts according to their severity using a Q-sort survey with members of the Cochrane Collaboration. RESULTS: We identified 39 types of spin, 28 from the main text and 21 from the abstract; 13 were specific to the systematic review design. Spin was classified into three categories: (1) misleading reporting, (2) misleading interpretation, and (3) inappropriate extrapolation. Spin ranked as the most severe by the 122 people who participated in the survey were (1) recommendations for clinical practice not supported by findings in the conclusion, (2) misleading title, and (3) selective reporting. CONCLUSION: This study allowed for identifying spin that is likely to distort interpretation. Our classification could help authors, editors, and reviewers avoid spin in reports of systematic reviews. PMID- 26845745 TI - GRADE guidelines system is reproducible when instructions are clearly operationalized even among the guidelines panel members with limited experience with GRADE. AB - OBJECTIVES: The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) is a widely used methodology for the development of clinical practice guideline. Although its reproducibility is good for evaluating the quality of evidence, it has not been tested in context of developing recommendations. The objective of this study was to assess the reproducibility of all GRADE factors that determine the direction and strength of a recommendation among the guideline panel members with limited exposure to GRADE methodology. STUDY DESIGN AND SETTING: The study was conducted as part of the clinical practice guideline development process of American Association of Blood Banking for the use of prophylactic vs. therapeutic platelet transfusion in patients with thrombocytopenia. The results from the systematic review and meta-analysis for each question were summarized as a GRADE evidence profile. Interrater agreement for all GRADE factors and strength of recommendations was summarized using a weighted kappa statistic with 95% confidence intervals (CI). RESULTS: Eighteen members of the panel participated in the deliberation of making recommendations and completed the online questionnaire. They were given two 1-hour lectures about GRADE. The agreement for all domains was better than chance. The interrater agreement for the domain of quality of evidence was good (kappa value: 0.68; 95% CIs: 0.54, 0.84), and fair for balance of benefit and harms (kappa value: 0.4; 95% CIs: 0.25, 0.57) and use of resources (kappa value: 0.28: 95% CIs: 0.12, 0.42). The interrater agreement was moderate for the GRADE domain of patients' values and preferences (kappa value: 0.44; 95% CI: 0.31, 0.56). The interrater agreement for making a for/against recommendation was good (kappa value: 0.74; 95% CIs: 0.33, 0.91) and fair for strong/weak recommendation (kappa value: 0.39; 95% CIs: 0.18, 0.68). CONCLUSIONS: Although not all elements of GRADE system had good agreement, the interrater agreement for assessing the quality of evidence and issuing a recommendation of for vs. against among panel members who had limited exposure to GRADE methodology was good. This is probably because GRADE has operationalized these two areas in more detail than other domains. Further operationalization of all GRADE domains such as with the GRADE evidence to decision frameworks would likely improve its reproducibility. PMID- 26845746 TI - There is no reverse hierarchy (letter commenting: J Clin Epidemiol. 2015;68(11):1251--1260.). PMID- 26845747 TI - The exchangeability of self-reports and administrative health care resource use measurements: assessement of the methodological reporting quality. AB - OBJECTIVE: To assess the exchangeability of self-reported and administrative health care resource use measurements for cost estimation. STUDY DESIGN AND SETTING: In a systematic review (NHS EED and MEDLINE), reviewers evaluate, in duplicate, the methodological reporting quality of studies comparing the validation evidence of instruments measuring health care resource use. The appraisal tool Methodological Reporting Quality (MeRQ) is developed by merging aspects form the Guidelines for Reporting Reliability and Agreement Studies and the Standards for Reporting Diagnostic Accuracy. RESULTS: Out of 173 studies, 35 full-text articles are assessed for eligibility. Sixteen articles are included in this study. In seven articles, more than 75% of the reporting criteria assessed by MERQ are considered "good." Most studies score at least "fair" on most of the reporting quality criteria. In the end, six studies score "good" on the minimal criteria for reporting. Varying levels of agreement among the different data sources are found, with correlations ranging from 0.14 up to 0.93 and with occurrences of both random and systematic errors. CONCLUSION: The validation evidence of the small number of studies with adequate MeRQ cautiously supports the exchangeability of both the self-reported and administrative resource use measurement methods. PMID- 26845749 TI - Deciphering the Conformational Choreography of Zinc Coordination Complexes with Standard and Novel Proton NMR Techniques Combined with DFT Methods. AB - The presence of water has been shown to deeply impact the stability and geometry of Zn complexes in solution. Evidence for tetra- and penta-coordinated species in a pyridylmethylamine-Zn(II) model complex is presented. Novel (1) H NMR tools such as T1 -filtered selective exchange spectroscopy and pure shifted gradient encoded selective refocusing as well as classical 2D ((1) H-(1) H) exchange spectroscopy, diffusion-ordered spectroscopy and T1 ((1) H) measurements, in combination with density functional theory methods allow the full conformational dynamics of a pyridylmethylamine-Zn(II) complex to be revealed. Four conformers and two families of complexes depending on the hydration states are elucidated. PMID- 26845750 TI - Alarmone (p)ppGpp regulates the transition from pathogenicity to mutualism in Photorhabdus luminescens. AB - The enteric gamma-proteobacterium Photorhabdus luminescens kills a wide range of insects, whilst also maintaining a mutualistic relationship with soil nematodes from the family Heterorhabditis. Pathogenicity is associated with bacterial exponential growth, whilst mutualism is associated with post-exponential (stationary) phase. During post-exponential growth, P. luminescens also elaborates an extensive secondary metabolism, including production of bioluminescence, antibiotics and pigment. However, the regulatory network that controls the expression of this secondary metabolism is not well understood. The stringent response is a well-described global regulatory system in bacteria and mediated by the alarmone (p)ppGpp. In this study, we disrupted the genes relA and spoT, encoding the two predicted (p)ppGpp synthases of P. luminescens TTO1, and we showed that (p)ppGpp is required for secondary metabolism. Moreover, we found the (p)ppGpp is not required for pathogenicity of P. luminescens, but is required for bacterial survival within the insect cadaver. Finally, we showed that (p)ppGpp is required for P. luminescens to support normal nematode growth and development. Therefore, the regulatory network that controls the transition from pathogenicity to mutualism in P. luminescens requires (p)ppGpp. This is the first report outlining a role for (p)ppGpp in controlling the outcome of an interaction between a bacteria and its host. PMID- 26845751 TI - Influence of Inert and Oxidizing Atmospheres on the Physical and Optical Properties of Luminescent Carbon Dots Prepared through Pyrolysis of a Model Molecule. AB - This work used L-tartaric acid as a model molecule to evaluate how the use of inert and oxidizing atmospheres during pyrolysis affected the physical and optical properties of the resulting carbon dots (CDs). Pyrolysis revealed to be a simple procedure that afforded CDs in a single step, dismissed the addition of organic solvents, and involved only one extraction stage that employed water. By X-ray diffraction a dependency between the structure of the CDs and the atmosphere (oxidizing or inert) used during the pyrolysis was found. Potentiometric titration demonstrated that the CDs were largely soluble in water; it also aided characterization of the various groups that contained sp(3) hybridized carbon atoms on the surface of the dots. Raman spectroscopy suggested that different amounts of sp(2)- and sp(3)-hybridized carbon atoms emerged on the CDs depending on the pyrolysis atmosphere. In conclusion, the pyrolysis atmosphere influenced the physical properties, such as the composition and the final structure. PMID- 26845752 TI - Effects of the Addition of Titanium Dioxide and Silaned Silica Nanoparticles on the Mechanical Properties of Maxillofacial Silicones. AB - PURPOSE: Silicone-based elastomeric materials are commonly used to fabricate maxillofacial prostheses. The aim of this study was to evaluate the effect of different types of silica and nanosized titanium dioxide addition on the mechanical properties of two RTV silicone elastomers. MATERIALS AND METHODS: A 2000 and A-2006 silicone elastomers were used, and each was divided into four subgroups (n = 5). The first group was the control without additives. Other groups were titanium dioxide, fumed silica, and silaned silica. Each specimen was prepared in compliance with the manufacturer's instructions for the tensile strength, percent elongation, tear resistance, and the hardness tests according to ISO and ASTM standards. A factorial ANOVA with pairwise interaction indicated that the pattern for all four outcomes of the materials was different for A-2000 and A-2006 (p < 0.05). Therefore, the average outcome values for the materials within silicone elastomers were then analyzed by Tukey HSD. For the hardness test results, Kruskal-Wallis and Mann-Whitney U test methods were used. The level of statistical significance was p < 0.05. RESULTS: There was a statistically significant interaction (p < 0.05) between materials and silicone type for all four tests (tensile strength, tear, hardness, percent elongation). The hydrophobic silica group had significantly higher tensile strength than TiO2 for A-2000. The fumed hydrophilic silica group had significantly higher tensile strength than TiO2 for A-2006. Most of silica specimens had higher tensile strength when compared with the control and TiO2 groups for A-2000 and A-2006 silicones. The TiO2 group had the highest hardness value for A-2000 while the lowest hardness value for A-2006 (p < 0.05). There was no significant difference of tear strength among the type of additives (p > 0.05) for A-2000. The fumed silica and TiO2 groups had significantly higher tear strength than the control group for A-2006. The fumed silica and the hydrophobic silica groups had significantly higher percent elongation than the control group (p < 0.05) for A 2000. The TiO2 group had the lowest percent elongation for A-2006. CONCLUSIONS: Results in this in vitro study may clarify future studies about the effect of different additives on the physical and mechanical properties of maxillofacial elastomers. There is a great interest in the effect of a new-generation hydrophobic silica incorporation into A-2000 silicone as well as the effect of fumed hydrophilic silica incorporation into A-2006 silicone. Future research should be supported with more in vitro trials in different percentages of such additives used in this study. PMID- 26845753 TI - Vitamin D3 for uncontrolled childhood asthma: A pilot study. AB - BACKGROUND: Observational and mechanistic data suggest a role for vitamin D in childhood asthma. However, subsequent interventional trials have been inconsistent. We aimed to assess the effect of 15 weeks of vitamin D3 supplementation compared with placebo (PL) in Irish children with asthma. METHODS: We conducted a double-blind, randomized, PL-controlled trial of vitamin D supplementation (2000 IU/day) in 44 urban, Caucasian children at high latitude. Assessments were completed at baseline and after 15 weeks of supplementation. Outcome measures were lung function, subjective asthma control and biochemical parameters of total vitamin D, allergy, immunity, airway inflammation, and systemic inflammation. Finally, parents/guardians completed a weekly diary during the trial. RESULTS: There was no significant difference in baseline 25(OH)D levels, but there was a significant increase in median 25(OH)D in the vitamin D3 group (57.5-105 nmol/l) compared with the PL group (52.5-57.5 nmol/l) (p < 0.0001). There was no significant difference between groups regarding subjective asthma control. Compared with PL, there was a significant decrease in school days missed due to asthma (1 vs. 5 days, p = 0.04) and alkaline phosphatase (-3.4 vs. +16; p = 0.037) in the vitamin D3 group, but there were no beneficial effects regarding several other secondary end-points. However, there were non significant, advantageous changes in the PL group compared with the vitamin D3 group in subjective asthma control and lung function, particularly percentage of predicted forced expiratory volume in 1 s (+2.5 vs. -4; p = 0.06). CONCLUSION: Vitamin D3 supplementation led to a significant increase in serum 25(OH)D and decreased school days missed (p = 0.04), but no other advantageous changes in asthma parameters compared with PL. The potential adverse effect of vitamin D deficiency on growth and the potential negative effect of high serum 25(OH)D on pulmonary function warrant further investigation. PMID- 26845754 TI - Prevalence of deep vein thrombosis and pulmonary embolism in patients with superficial vein thrombosis: a systematic review and meta-analysis. AB - Essentials The association of superficial vein thrombosis (SVT) with venous thromboembolism (VTE) is variable. We performed a meta-analysis to assess the prevalence of concomitant VTE in patients with SVT. Deep vein thrombosis was found in 18.1%, and pulmonary embolism in 6.9%, of SVT patients. Screening for VTE may be worthy in some SVT patients to plan adequate anticoagulant treatment. SUMMARY: Background Some studies have suggested that patients with superficial vein thrombosis (SVT) have a non-negligible risk of concomitant deep vein thrombosis (DVT) or pulmonary embolism (PE) at the time of SVT diagnosis. Unfortunately, the available data on this association are widely variable. Objectives To perform a systematic review and meta-analysis of the literature in order to evaluate the prevalence of concomitant DVT/PE in patients with SVT of the lower limbs. Methods Studies reporting on the presence of DVT/PE in SVT patients were systematically searched for in the PubMed, Web of Science, Scopus and EMBASE databases. The weighted mean prevalence (WMP) of DVT and PE was calculated by use of the random effect model. Results Twenty-one studies (4358 patients) evaluated the prevalence of DVT and 11 studies (2484 patients) evaluated the prevalence of PE in patients with SVT. The WMP of DVT at SVT diagnosis was 18.1% (95%CI: 13.9%, 23.3%) and the WMP of PE was 6.9% (95%CI: 3.9%, 11.8%). Heterogeneity among the studies was substantial. Selection of studies including outpatients only gave similar results (WMP of DVT, 18.2%, 95% CI 12.2-26.3%; and WMP of PE, 8.2%, 95% CI 3.3-18.9%). Younger age, female gender, recent trauma and pregnancy were inversely associated with the presence of DVT/PE in SVT patients. Conclusions The results of our large meta-analysis suggest that the prevalence of DVT and PE in patients presenting with SVT is not negligible. Screening for a major thromboembolic event may be worthwhile in some SVT patients, in order to allow adequate anticoagulant treatment to be planned. Other high-quality studies are warranted to confirm our findings. PMID- 26845755 TI - Underutilization of Timely Kidney Transplants in Those With Living Donors. AB - Preemptive kidney transplant (PKTx) and kidney transplant (KTx) within 1 year of dialysis initiation have been associated with superior outcomes. Wait times should be minimal for transplants with living donors; however, there is lack of literature studying utilization of timely KTx in this population. We designed this retrospective study using data from United Network for Organ Sharing Standard Transplant Analysis and Research files from 2000 to 2012 to assess the trends in utilization of PKTx and Early KTx (combination of PKTx or transplant within 1 year of dialysis initiation) in recipients of living donor KTx. Only 32.6% transplants were PKTx, and 61.9% were Early KTx. A significant improvement in proportion of PKTx was seen from 27.5% in 2000 to 35.4% in 2006, with no change since. Similarly, the proportion of Early KTx increased from 61.4% in 2000 to 63.6% in 2006, with no increase since. Similar results were seen after adjusted analysis and were independent of living donor type. Although there was some improvement in utilization of timely transplants in the early part of the last decade, there has been no improvement since. Considering the benefits of timely kidney transplant, it is important to understand the reasons behind the same and to improve utilization. PMID- 26845756 TI - Integrating the pace-of-life syndrome across species, sexes and individuals: covariation of life history and personality under pesticide exposure. AB - The pace-of-life syndrome (POLS) hypothesis integrates covariation of life history traits along a fast-slow continuum and covariation of behavioural traits along a proactive-reactive personality continuum. Few studies have investigated these predicted life-history/personality associations among species and between sexes. Furthermore, whether and how contaminants interfere with POLS patterns remains unexplored. We tested for covariation patterns in life history and in behaviour, and for life-history/personality covariation among species, among individuals within species and between sexes. Moreover, we investigated whether pesticide exposure affects covariation between life history and behaviour and whether species and sexes with a faster POLS strategy have a higher sensitivity to pesticides. We reared larvae of four species of Ischnura damselflies in a common garden experiment with an insecticide treatment (chlorpyrifos absent/present) in the final instar. We measured four life-history traits (larval growth rate during the pesticide treatment, larval development time, adult mass and life span) and two behavioural traits (larval feeding activity and boldness, each before and after the pesticide treatment). At the individual level, life history traits and behavioural traits aligned along a fast-slow and a proactive reactive continuum, respectively. Species-specific differences in life history, with fast-lived species having a faster larval growth and development, a lower mass at emergence and a shorter life span, suggested that time constraints in the larval stage were predictably driving life-history evolution both in the larval stage and across metamorphosis in the adult stage. Across species, females were consistently more slow-lived than males, reflecting that a large body size and a long life span are generally more important for females. In contrast to the POLS hypothesis, there was only little evidence for the expected positive coupling between life-history pace and proactivity. Pesticide exposure decreased larval growth rate and affected life-history/personality covariation in the most fast lived species. Our study supports the existence of life-history and behavioural continua with limited support for life-history/personality covariation. Variation in digestive physiology may explain this decoupling of life history and behaviour and provide valuable mechanistic insights to understand and predict the occurrence of life-history/personality covariation patterns. PMID- 26845757 TI - Mesenchymal/radioresistant traits in granular astrocytomas: evidence from a combined clinical and molecular approach. AB - AIMS: Granular-cell astrocytomas (GCAs) are morphologically characterized by a prominent component of granular periodic acid-Schiff-positive cells, and show increased aggressiveness as compared with 'ordinary' astrocytomas. The aim of this study was to investigate, in a small series of three GCAs, the expression of mesenchymal/radioresistance-associated biomarkers [such as chitinase-3-like protein 1 (YKL-40), hepatocyte growth factor receptor (c-Met), and caveolin 1 (Cav1)] that could contribute to the poor outcome associated with this glioma subgroup. METHODS AND RESULTS: Our results show that GCAs, according to the new molecular glioma classifications, consistently show a prognostically negative molecular trait (IDH1wt-ATRX noloss-1p/19q nocodeletion). Furthermore, GCAs significantly differed from a control series of 33 'conventional' astrocytomas, because of diffuse and strong immunohistochemical coexpression of YKL-40, c-Met, and Cav1. CONCLUSIONS: Our findings show that specific morphological traits, such as a granular-cell component, could represent useful features in guiding the search for prognostic and predictive biomarkers that could eventually be therapy targetable (e.g. Met inhibitors aimed at reducing radioresistance). PMID- 26845759 TI - Drug-drug co-crystallization presents a new opportunity for the development of stable vitamins. AB - Drug-drug co-crystallization could realize combination drugs at a molecular level. Two polymorphic co-crystals between VD2 and VD3 were successfully designed and synthesized. These enantiotropic polymorphs exhibit significantly different physicochemical stabilities. PMID- 26845758 TI - c-Jun N-terminal kinase mediates mouse liver injury through a novel Sab (SH3BP5) dependent pathway leading to inactivation of intramitochondrial Src. AB - Sustained c-Jun N-terminal kinase (JNK) activation has been implicated in many models of cell death and tissue injury. Phosphorylated JNK (p-JNK) interacts with the mitochondrial outer membrane SH3 homology associated BTK binding protein (Sab, or SH3BP5). Using knockdown or liver-specific deletion of Sab, we aimed to elucidate the consequences of this interaction on mitochondrial function in isolated mitochondria and liver injury models in vivo. Respiration in isolated mitochondria was directly inhibited by p-JNK + adenosine triphosphate. Knockdown or liver-specific knockout of Sab abrogated this effect and markedly inhibited sustained JNK activation and liver injury from acetaminophen or tumor necrosis factor/galactosamine. We then elucidated an intramitochondrial pathway in which interaction of JNK and Sab on the outside of the mitochondria released protein tyrosine phosphatase, nonreceptor type 6 (SHP1, or PTPN6) from Sab in the inside of the mitochondrial outer membrane, leading to its activation and transfer to the inner membrane, where it dephosphorylates P-Y419Src (active), which required a platform protein, docking protein 4 (DOK4), on the inner membrane. Knockdown of mitochondrial DOK4 or SHP1 inhibited the inactivation of mitochondrial p-Src and the effect of p-JNK on mitochondria. CONCLUSIONS: The binding to and phosphorylation of Sab by p-JNK on the outer mitochondrial membrane leads to SHP1 dependent and DOK4-dependent inactivation of p-Src on the inner membrane; inactivation of mitochondrial Src inhibits electron transport and increases reactive oxygen species release, which sustains JNK activation and promotes cell death and organ injury. (Hepatology 2016;63:1987-2003). PMID- 26845760 TI - A New Approach for Deep Gray Matter Analysis Using Partial-Volume Estimation. AB - INTRODUCTION: The existence of partial volume effects in brain MR images makes it challenging to understand physio-pathological alterations underlying signal changes due to pathology across groups of healthy subjects and patients. In this study, we implement a new approach to disentangle gray and white matter alterations in the thalamus and the basal ganglia. The proposed method was applied to a cohort of early multiple sclerosis (MS) patients and healthy subjects to evaluate tissue-specific alterations related to diffuse inflammatory or neurodegenerative processes. METHOD: Forty-three relapsing-remitting MS patients and nineteen healthy controls underwent 3T MRI including: (i) fluid attenuated inversion recovery, double inversion recovery, magnetization-prepared gradient echo for lesion count, and (ii) T1 relaxometry. We applied a partial volume estimation algorithm to T1 relaxometry maps to gray and white matter local concentrations as well as T1 values characteristic of gray and white matter in the thalamus and the basal ganglia. Statistical tests were performed to compare groups in terms of both global T1 values, tissue characteristic T1 values, and tissue concentrations. RESULTS: Significant increases in global T1 values were observed in the thalamus (p = 0.038) and the putamen (p = 0.026) in RRMS patients compared to HC. In the Thalamus, the T1 increase was associated with a significant increase in gray matter characteristic T1 (p = 0.0016) with no significant effect in white matter. CONCLUSION: The presented methodology provides additional information to standard MR signal averaging approaches that holds promise to identify the presence and nature of diffuse pathology in neuro inflammatory and neurodegenerative diseases. PMID- 26845761 TI - Long-Term Benefits of Smoking Cessation on Gastroesophageal Reflux Disease and Health-Related Quality of Life. AB - OBJECTIVE: Smoking is associated with gastroesophageal reflux disease (GERD). Varenicline, a nicotinic receptor partial agonist, is used to aid smoking cessation. The purpose of this study was to prospectively examine the long-term benefits of smoking cessation on GERD and health-related quality of life (HR QOL). METHODS: Patients treated with varenicline were asked to fill out a self report questionnaire about their smoking habits, gastrointestinal symptoms, and HR-QOL before and 1 year after smoking cessation. The prevalence of GERD, frequency of symptoms, and HR-QOL scores were compared. We also investigated associations between clinical factors and newly-developed GERD. RESULTS: A total of 141 patients achieved smoking cessation (success group) and 50 did not (failure group) at 1 year after the treatment. The GERD improvement in the success group (43.9%) was significantly higher than that in the failure group (18.2%). The frequency of reflux symptoms significantly decreased only in the success group. There were no significant associations between newly developed GERD and clinical factors including increased body mass index and successful smoking cessation. HR-QOL significantly improved only in the success group. CONCLUSIONS: Smoking cessation improved both GERD and HR-QOL. Smoking cessation should be recommended for GERD patients. PMID- 26845762 TI - Incidence of Dengue Virus Infection in Adults and Children in a Prospective Longitudinal Cohort in the Philippines. AB - BACKGROUND: The mean age of dengue has been increasing in some but not all countries. We sought to determine the incidence of dengue virus (DENV) infection in adults and children in a prospective cohort study in the Philippines where dengue is hyperendemic. METHODOLOGY/PRINCIPAL FINDINGS: A prospective cohort of subjects >=6 months old in Cebu City, Philippines, underwent active community based surveillance for acute febrile illnesses by weekly contact. Fever history within the prior seven days was evaluated with an acute illness visit followed by 2, 5, and 8-day, and 3-week convalescent visits. Blood was collected at the acute and 3-week visits. Scheduled visits took place at enrolment and 12 months that included blood collections. Acute samples were tested by DENV PCR and acute/convalescent samples by DENV IgM/IgG ELISA to identify symptomatic infections. Enrolment and 12-month samples were tested by DENV hemagglutination inhibition (HAI) assay to identify subclinical infections. Of 1,008 enrolled subjects, 854 completed all study activities at 12 months per-protocol undergoing 868 person-years of surveillance. The incidence of symptomatic and subclinical infections was 1.62 and 7.03 per 100 person-years, respectively. However, in subjects >15 years old, only one symptomatic infection occurred whereas 27 subclinical infections were identified. DENV HAI seroprevalence increased sharply with age with baseline multitypic HAIs associated with fewer symptomatic infections. Using a catalytic model, the historical infection rate among dengue naive individuals was estimated to be high at 11-22%/year. CONCLUSIONS/SIGNIFICANCE: In this hyperendemic area with high seroprevalence of multitypic DENV HAIs in adults, symptomatic dengue rarely occurred in individuals older than 15 years. Our findings demonstrate that dengue is primarily a pediatric disease in areas with high force of infection. However, the average age of dengue could increase if force of infection decreases over time, as is occurring in some hyperendemic countries such as Thailand. PMID- 26845765 TI - Mechanism of a Mutation in Non-Structural Protein 1 Inducing High Pathogenicity of Avian Influenza Virus H5N1. AB - Avian influenza H5N1 has shown high mortality rate in human. Non-structural protein 1 (NS1) is a virulence factor of H5N1. Mutation at the 42nd residue within the RNA-binding domain (RBD) of NS1 dramatically changes the degree of pathogenicity of H5N1 in mice. We here studied the impact of this mutation on the function of RBD, and found that RBD with serine at the 42th residue binds double stranded RNA (dsRNA), whereas that with proline at the 42th residue does not. Analysis of structural models of the RBD proteins with S42 and P42 suggested remarkable difference in the structure of the dsRNA-binding interface, whereas structural analysis by analytical gel filtration and CD measurements did not indicate difference between those RBD proteins. Our results suggest that the single amino acid replacement induces a minor, but global structural change leading to the loss of function of NS1 thereby the change in the degree of pathogenicity. PMID- 26845763 TI - Computational Cancer Biology: An Evolutionary Perspective. PMID- 26845764 TI - Genomic Signatures for Avian H7N9 Viruses Adapting to Humans. AB - An avian influenza A H7N9 virus emerged in March 2013 and caused a remarkable number of human fatalities. Genome variability in these viruses may provide insights into host adaptability. We scanned over 140 genomes of the H7N9 viruses isolated from humans and identified 104 positions that exhibited seven or more amino acid substitutions. Approximately half of these substitutions were identified in the influenza ribonucleoprotein (RNP) complex. Although PB2 627K of the avian virus promotes replication in humans, 45 of the 147 investigated PB2 sequences retained the E signature at this position, which is an avian characteristic. We discovered 10 PB2 substitutions that covaried with K627E. An RNP activity assay showed that Q591K, D701N, and M535L restored the polymerase activity in human cells when 627K transformed to an avian-like E. Genomic analysis of the human-isolated avian influenza virus is crucial in assessing genome variability, because relationships between position-specific variations can be observed and explored. In this study, we observed alternative positions that can potentially compensate for PB2 627K, a well-known marker for cross species infection. An RNP assay suggested Q591K, D701N, and M535L as potential markers for an H7N9 virus capable of infecting humans. PMID- 26845766 TI - Polymorphism of the Cysteine Protease YopT from Yersinia pestis. AB - Antibiotic therapy of plague is hampered by the recent isolation of Yersinia pestis strain resistant to all of antibiotics recommended for cure. This has constrained a quest for new antimicrobials taking aim at alternative targets. Recently Y. pestis cysteine protease YopT has been explored as a potential drug target. Targets conserved in the pathogen populations should be more efficacious; therefore, we evaluated intraspecies variability in yopT genes and their products. 114 Y. pestis isolates were screened. Only two YopT full-size isoforms were found among them. The endemic allele (N149) was present in biovar caucasica from Dagestan-highland natural plague focus # 39. The biovar caucasica strains from Transcaucasian highland (# 4-6) and Pre-Araks (# 7) plague foci also contained the N149 allele. These strains from foci # 4 7 possessed a truncated version of YopT that was a consequence of a frame-shift due to the deletion of a single nucleotide at position 71 bp. Computational analyses showed that although the SNP at the position 149 has a very minimal effect of the intrinsic disorder propensity of YopT proteins, whereas the N-terminal truncations of the YopT detected in bv. caucasica strains Pestoides F_YopT1 and F_YopT2, and Pestoides G generated isoforms with the significantly modified intrinsic disorder propensities and with reduced capability to interact with lost ability to utilize their N-terminal tail for the disorder-based interactions with biological partners. Considering that representatives of biovar caucasica were reported to be the reason of sporadic cases of human plague, this study supports the necessity of additional testing of globally disseminated YopT (S149) isoform as a potential target for treatment of plague caused by the strains producing different YopT isoforms. PMID- 26845767 TI - Novel Application of Peptidyl-Lys Metallopeptidase as a C-Terminal Processing Protease. AB - Adding fusion partners to proteins or peptides can aid or be a necessity to facilitate recombinant expression, folding, or purification. Independent of the reason it is desirable to remove the fusion partner to restore native functionality. Processing proteases catalyze the removal of fusion partners, however, most of these proteases have substrate specificity for the N-terminal of the scissile bond, leaving non-native termini if fusions are added to the C terminal. The peptidyl-lys metallopeptidease of Armillaria mellea (Am-LysN) is unusual by having substrate specificity for the C-terminal side of the scissile peptide bond, allowing it to generate native C-termini. Am-LysN has strict specificity for lysine in P1', making all lysines of a protein or peptide a potential degradation site, however there are a number of amino acid side chains which lower hydrolysis significantly when located adjacent to the lysine. In this study we show that Am-LysN can be used as a processing protease to remove C terminal extensions of peptides with no internal lysine to generate native Ctermini. Furthermore we show that removal of C-terminal extensions on peptides containing internal lysines can be achieved with little degradation of the product depending on the adjacent amino acids. These results demonstrate the utility of LysN allowing for novel ways to use fusion technology in the production of recombinant proteins. PMID- 26845768 TI - Obestatin and Ghrelin May Have a Complementary Function During Acute and Chronic Period in Mice. AB - Obestatin is described as an anorexigenic peptide, and has adverse effects of ghrelin. It has no inhibitory effects on acute/chronic food intake, and it has been reported by several researchers. The role of obestatin in metabolism is still not clear. In the present study, the purpose is to determine the effects of chronically administrated obestatin. For this purpose, (1 umol/kg; i.p.) or ghrelin (1 umol/kg; i.p.) and food restriction (24h fast:24h fed) on plasma obestatin, ghrelin, leptin, insulin, cholecystokinin (CCK) and glucose levels, and body weight gain were investigated for 14 days in mice. Additionally, mice were treated with acute ip (100 nmol/kg) injections of obestatin or ghrelin to investigate the food consumptions, plasma obestatin and ghrelin levels to determine unknown acute effects of obestatin. Plasma ghrelin levels increased significantly in obestatin administered mice when compared with the control group for chronic treatment. This increase is consistent with immunohistochemical findings which claim that the number of ghrelin and obestatin immunopositive cells in fundus tissue of stomach are considerably high in obestatin treated animals. Plasma obestatin and ghrelin levels has shown an increase endogenously in food restricted mice, but plasma leptin and insulin levels have been found to be lower compared to the control group. Acute administration of obestatin caused a decrease in plasma obestatin level at 60 min after injection and had no effect on the reduction of food intake in each treatment time. These results imply that obestatin may not itself be involved in the metabolism regulation; however, obestatin accompanied by ghrelin may play a role in the long-term regulation of metabolism. PMID- 26845769 TI - On the Interaction Between Human IQGAP1 and Actin. AB - IQGAPs are eukaryotic proteins which integrate signals from various sources and pass these on the cytoskeleton. Understanding how they do this requires information on the interfaces between the proteins. Here, it is shown that the calponin homology domain of human IQGAP1 (CHD1) can be crosslinked with alpha actin. The stoichiometry of the interaction was 1:1. A molecular model was built of the complex and associated bioinformatics analyses predicted that the interaction is likely to involve an electrostatic interaction between Lys-240 of alpha-actin and Glu-30 of CHD1. These residues are predicted to be accessible and are not involved in many intra-protein interactions; they are thus available for interaction with binding partners. They are both located in regions of the proteins which are predicted to be flexible and disordered; interactions between signalling molecules often involve flexible, disordered regions. The predicted binding region in CHD1 is well conserved in many eukaryotic IQGAP-like proteins. In some cases (e.g Dictyostelium discoideum and Saccharomyces cerevisiae) protein sequence conservation is weak, but molecular modelling reveals that a region of charged, polar residues in a flexible N-terminus is structurally well conserved. Therefore we conclude that the calponin homology domains of IQGAP1-like proteins interact initially through the electrostatic interaction identified here and that there may be subsequent conformational changes to form the final complex. PMID- 26845770 TI - The Symbiotic Performance of Chickpea Rhizobia Can Be Improved by Additional Copies of the clpB Chaperone Gene. AB - The ClpB chaperone is known to be involved in bacterial stress response. Moreover, recent studies suggest that this protein has also a role in the chickpea-rhizobia symbiosis. In order to improve both stress tolerance and symbiotic performance of a chickpea microsymbiont, the Mesorhizobium mediterraneum UPM-Ca36T strain was genetically transformed with pPHU231 containing an extra-copy of the clpB gene. To investigate if the clpB-transformed strain displays an improved stress tolerance, bacterial growth was evaluated under heat and acid stress conditions. In addition, the effect of the extra copies of the clpB gene in the symbiotic performance was evaluated using plant growth assays (hydroponic and pot trials). The clpB-transformed strain is more tolerant to heat shock than the strain transformed with pPHU231, supporting the involvement of ClpB in rhizobia heat shock tolerance. Both plant growth assays showed that ClpB has an important role in chickpea-rhizobia symbiosis. The nodulation kinetics analysis showed a higher rate of nodule appearance with the clpB-transformed strain. This strain also induced a greater number of nodules and, more notably, its symbiotic effectiveness increased ~60% at pH5 and 83% at pH7, compared to the wild-type strain. Furthermore, a higher frequency of root hair curling was also observed in plants inoculated with the clpB-transformed strain, compared to the wild-type strain. The superior root hair curling induction, nodulation ability and symbiotic effectiveness of the clpB-transformed strain may be explained by an increased expression of symbiosis genes. Indeed, higher transcript levels of the nodulation genes nodA and nodC (~3 folds) were detected in the clpB-transformed strain. The improvement of rhizobia by addition of extra-copies of the clpB gene may be a promising strategy to obtain strains with enhanced stress tolerance and symbiotic effectiveness, thus contributing to their success as crop inoculants, particularly under environmental stresses. This is the first report on the successful improvement of a rhizobium with a chaperone gene. PMID- 26845771 TI - Parvovirus B19 Replication and Expression in Differentiating Erythroid Progenitor Cells. AB - The pathogenic Parvovirus B19 (B19V) is characterized by a strict adaptation to erythroid progenitor cells (EPCs), a heterogeneous population of differentiating cells with diverse phenotypic and functional properties. In our work, we studied the dynamics of B19V infection in EPCs in dependence on the cell differentiation stage, in terms of distribution of infected cells, synthesis of viral nucleic acids and production of infectious virus. EPCs at early differentiation stage led to an abortive infection, without viral genome replication and a very low transcriptional activity. EPCs at later stages were permissive, with highest levels of viral replicative activity at day 9 (+3.0 Log from 2 to 48 hpi) and lower levels at day 18 (+1.5 Log from 2 to 48 hpi). B19V DNA increment was in accordance with the percentage of cells positive to flow-FISH assay (41.4% at day 9, 1.1% at day 18). Quantitation of total RNA indicated a close association of genome replication and transcription with viral RNA accumulation within infected cells related to viral DNA increase during the course of infection. Analysis of the different classes of mRNAs revealed two distinct pattern of genome expression profile with a fine regulation in the frequency utilization of RNA processing signals: an early phase, when cleavage at the proximal site leading to a higher relative production of mRNA for NS protein, and a late phase, when cleavage at the distal site was more frequent leading to higher relative abundance of mRNA for VP and 11 kDA proteins. Infectious virus was released from cells at day 6-15, but not at day 18. Our results, providing a detailed description of B19V replication and expression profile in differentiating EPCs, highlight the very tight adaptation of B19V to a specific cellular target defined both by its erythroid lineage and its differentiation stage. PMID- 26845773 TI - Measuring Stuttering in Preschool-Aged Children across Different Languages: An International Study. AB - BACKGROUND/AIMS: Many speech-language pathologists (SLPs) are working in linguistically diverse communities and have to identify and measure stuttering in a language other than their own. The aim of the present study was to extend our understanding of how well SLPs can measure stuttering in other languages and to encourage collaboration between SLPs across cultures. METHODS: Speech samples consisted of seven preschool-aged children each speaking one of the following languages: Danish, English, French, German, Greek, Italian, and Persian (Farsi). The judges were classified in seven groups of SLPs (n = 170) each speaking one of the seven languages of the children and two more English-speaking groups. Each judge rated the severity of stuttering in each child using a 10-point scale. The study was conducted over the Internet. RESULTS: Overall, the judges' proficiency in a child's language was not systematically related to the variability and agreement of the severity ratings, accounting for maximally 4.6% of the variance. CONCLUSION: SLPs should not be overly concerned about the appropriateness of their severity ratings if they feel less proficient in the native language of the stuttering children. It may also be encouraging for beginning clinicians that the severity ratings were not systematically related to professional experience. PMID- 26845772 TI - The Many Organisational Factors Relevant to Planning Change in Emergency Care Departments: A Qualitative Study to Inform a Cluster Randomised Controlled Trial Aiming to Improve the Management of Patients with Mild Traumatic Brain Injuries. AB - BACKGROUND: The Neurotrauma Evidence Translation (NET) Trial aims to design and evaluate the effectiveness of a targeted theory-and evidence-informed intervention to increase the uptake of evidence-based recommended practices for the management of patients who present to an emergency department (ED) with mild head injuries. When designing interventions to bring about change in organisational settings such as the ED, it is important to understand the impact of the context to ensure successful implementation of practice change. Few studies explicitly use organisational theory to study which factors are likely to be most important to address when planning change processes in the ED. Yet, this setting may have a unique set of organisational pressures that need to be taken into account when implementing new clinical practices. This paper aims to provide an in depth analysis of the organisational context in which ED management of mild head injuries and implementation of new practices occurs, drawing upon organisational level theory. METHODS: Semi-structured interviews were conducted with ED staff in Australia. The interviews explored the organisational context in relation to change and organisational factors influencing the management of patients presenting with mild head injuries. Two researchers coded the interview transcripts using thematic content analysis. The "model of diffusion in service organisations" was used to guide analyses and organisation of the results. RESULTS: Nine directors, 20 doctors and 13 nurses of 13 hospitals were interviewed. With regard to characteristics of the innovation (i.e. the recommended practices) the most important factor was whether they were perceived as being in line with values and needs. Tension for change (the degree to which stakeholders perceive the current situation as intolerable or needing change) was relatively low for managing acute mild head injury symptoms, and mixed for managing longer-term symptoms (higher change commitment, but relatively low change efficacy). Regarding implementation processes, the importance of (visible) senior leadership for all professions involved was identified as a critical factor. An unpredictable and hectic environment brings challenges in creating an environment in which team-based and organisational learning can thrive (system antecedents for innovation). In addition, the position of the ED as the entry point of the hospital points to the relevance of securing buy-in from other units. CONCLUSIONS: We identified several organisational factors relevant to realising change in ED management of patients who present with mild head injuries. These factors will inform the intervention design and process evaluation in a trial evaluating the effectiveness of our implementation intervention. PMID- 26845774 TI - Screening of Drug Metabolizing Enzymes for the Ginsenoside Compound K In Vitro: An Efficient Anti-Cancer Substance Originating from Panax Ginseng. AB - Ginsenoside compound K (CK), a rare ginsenoside originating from Panax Ginseng, has been found to possess unique pharmacological activities specifically as anti cancers. However, the role of cytochrome P450s (CYPs) in the metabolism of CK is unclear. In this study, we screened the CYPs for the metabolism of CK in vitro using human liver microsomes (HLMs) or human recombinant CYPs. The results showed that CK inhibited the enzyme activities of CYP2C9 and CYP3A4 in the HLMs. The Km and Vmax values of CK were 84.20+/-21.92 MUM and 0.28+/-0.04 nmol/mg protein/min, respectively, for the HLMs; 34.63+/-10.48 MUM and 0.45+/-0.05 nmol/nmol P450/min, respectively, for CYP2C9; and 27.03+/-5.04 MUM and 0.68+/-0.04 nmol/nmol P450/min, respectively, for CYP3A4. The IC50 values were 16.00 MUM and 9.83 MUM, and Ki values were 14.92 MUM and 11.42MUM for CYP2C9 and CYP3A4, respectively. Other human CYP isoforms, including CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP2C19, showed minimal or no effect on CK metabolism. The results suggested that CK was a substrate and also inhibitors for both CYP2C9 and CYP3A4. Patients using CK in combination with therapeutic drugs that are substrates of CYP2C9 and CYP3A4 for different reasons should be careful, although the inhibiting potency of CK is much poorer than that of enzyme-specific inhibitors. PMID- 26845776 TI - Presence of Atrial Fibrillation at the Time of Dialysis Initiation Is Associated with Mortality and Cardiovascular Events. AB - BACKGROUND: Death in dialysis patients results mainly from cardiovascular and cerebrovascular diseases. To our knowledge, no prospective study has compared the rates of mortality or cardiovascular events between patients with and without atrial fibrillation (AF) at the time of dialysis initiation. METHODS: This study included 1,516 patients who were initiated into dialysis between October 2011 and August 2013. Rates of mortality and cardiovascular events were compared between patients with and without AF, and between AF patients with and without warfarin (WF) treatment. RESULTS: The study comprised 1,025 men and 491 women with a mean age of 67.5 +/- 13.1. Of these patients, 93 had AF, while 1,423 did not; 22.6% of the former group and 9.7% of the latter group died by March 2014 (p < 0.01). Cardiovascular events occurred in 34.4% of patients with AF and 15.1% of patients without (p < 0.01). Even after adjustments for various factors, AF remained an independent risk factor for mortality (hazard ratio (HR) 1.873, 95% CI 1.168 3.002, p < 0.01). It was also an independent risk factor for cardiovascular events (HR 1.872, 95% CI 1.262-2.778, p < 0.01). No difference in any parameter was noted between the groups that did and did not receive WF treatment. CONCLUSION: Patients with AF at the time of dialysis initiation show a poor prognosis and are at high risk of cardiovascular events. Therefore, AF should be taken into consideration in dialysis patients. PMID- 26845775 TI - Di (2-ethylhexyl) Phthalate Exposure Impairs Growth of Antral Follicle in Mice. AB - Di (2-ethylhexyl) phthalate (DEHP) is a widely used plastic additive. As an environmental endocrine disruptor, it has been shown to be harmful to the mammalian reproductive system. Previous studies indicated that DEHP inhibited the development of mouse ovarian follicles. However, the mechanisms by which DEHP affects ovarian antral follicle development during the pre-puberty stage are poorly understand. Thus, we investigated the effects of direct DEHP exposure on antral follicle growth in pre-pubescent mice by use of intraperitoneal injection. Our results demonstrated that the percentage of large antral follicles was significantly reduced when mice were exposed to 20 or 40 MUg/kg DEHP every 5 days from postnatal day 0 (0 dpp) to 15 dpp. In 20 dpp, we performed microarray of these ovaries. The microarray results indicated that mRNA levels of apoptosis related genes were increased. The mRNA levels of the apoptosis and cell proliferation (negative) related genes Apoe, Agt, Glo1 and Grina were increased after DEHP exposure. DEHP induced the differential gene expression of Hsp90ab1, Rhoa, Grina and Xdh which may play an important role in this process. In addition, TUNEL staining and immunofluorescence showed that DEHP exposure significantly increased the number of TUNEL, Caspase3 and gammaH2AX positive ovarian somatic cells within the mouse ovaries. Flow cytometer analyses of redox sensitive probes showed that DEHP caused the accumulation of reactive oxygen species. Moreover, the mRNA expression of ovarian somatic cell antioxidative enzymes was down-regulated both in vivo and in vitro. In conclusion, our data here demonstrated that DEHP exposure induced oxidative stress and ovarian somatic cell apoptosis, and thus may impact antral follicle enlargement during the pre pubertal stage in mice. PMID- 26845777 TI - How do medical educators design a curriculum that facilitates student learning about professionalism? AB - OBJECTIVE: This study analyses the ways in which curriculum reform facilitated student learning about professionalism. METHODS: Design-based research provided the structure for an iterative approach to curriculum change which we undertook over a 3 year period. The learning environment of the Personal and Professional Development Theme (PPD) was analysed through the sociocultural lens of Activity Theory. Lave and Wenger's and Mezirow's learning theories informed curriculum reform to support student development of a patient-centred and critically reflective professional identity. The renewed pedagogical outcomes were aligned with curriculum content, learning and teaching processes and assessment, and intense staff education was undertaken. We analysed qualitative data from tutor interviews and free-response student surveys to evaluate the impact of curriculum reform. RESULTS: Students' and tutors' reflections on learning in PPD converged on two principle themes--'Developing a philosophy of medicine' and 'Becoming an ethical doctor'--which corresponded to the overarching PPD theme aims of communicative learning. Students and tutors emphasised the importance of the unique learning environment of PPD tutorials for nurturing personal development and the positive impact of the renewed assessment programme on learning. CONCLUSIONS: A theory-led approach to curriculum reform resulted in student engagement in the PPD curriculum and facilitated a change in student perspective about the epistemological foundation of medicine. PMID- 26845778 TI - Failure or Success?. PMID- 26845779 TI - Addendum: Diet, Drugs, and Surgery for Weight Loss. PMID- 26845780 TI - Facing the facts. PMID- 26845781 TI - Response. PMID- 26845782 TI - When saying no means no. PMID- 26845783 TI - Terms and conditions. PMID- 26845784 TI - Sharps rules not followed. PMID- 26845785 TI - NHS "hourglass" structure holds back development of support workforce. PMID- 26845786 TI - Vulnerability in perioperative patients: a qualitative study. AB - The study aimed to explore perioperative practitioners' knowledge, awareness and experiences of perioperative vulnerability in clinical practice. A qualitative descriptive design was used; data was obtained by conducting semi-structured interviews with ten perioperative practitioners over a two week period in July 2014. The study found that perioperative practitioners were aware of the concept of perioperative vulnerability and had varied experience of it in practice. Data analysis identified three main themes in relation to vulnerability: labels, recognition and management. We conclude that the concept of perioperative vulnerability exists in practice and that perioperative practitioners manage the concept effectively using strategies that promote positive outcomes. PMID- 26845787 TI - Awake and unable to move: what can perioperative practitioners do to avoid accidental awareness under general anaesthesia? AB - I thought the last thing I would remember about my surgery was counting up to 10 ... but that didn't happen... I could hear people talking, instruments banging, the sound of my heart beat coming from the anaesthetic machine and all of a sudden, that horrible pain digging inside my body. Oh my God! I thought. I'm awake! I tried to tell someone but no sound came out of my mouth. I tried to kick my legs, shake my arms, blink, breathe... Nothing!! I couldn't move a muscle. I was paralysed and awake during my operation... I thought I was going to die!!! PMID- 26845788 TI - Perioperative management of traumatic limb amputations due to civilian trauma: current practice and future directions. AB - Traumatic limb amputations are serious injuries. They require urgent multidisciplinary management and emergency surgical intervention to save life and, where possible, preserve limb function. It is therefore vital that perioperative management follows established evidence-based principles to optimise outcomes. In recent years a vast quantity of research on traumatic amputations in the military setting has been published, but civilian injuries, which often have strikingly different mechanisms, have been neglected. This article reviews existing information on epidemiology, pathophysiology, perioperative management strategies, outcomes and future directions in the field. PMID- 26845789 TI - The effect of anaemia on hospital length of stay in lumbar decompression and fusion procedures. AB - Ways of reducing the length of hospital stay have received increased attention in recent years. Both preoperative and postoperative anaemia have been implicated as causative agents in increasing postoperative length of stay (LOS). In a retrospective study, 317 patients that underwent lumbar decompression and fusion surgery were assessed. Two separate block multivariate linear regression analyses were performed to evaluate the impact of preoperative anaemia, postoperative anaemia, and the degree of perioperative haemoglobin drop on LOS. Other anaemia related factors were also assessed. Preoperative anaemia, postoperative anaemia, and the amount of perioperative haemoglobin drop were all shown to prolong the length of hospitalisation and therefore to increase overall healthcare costs. Following strict anaemia corrective maneuvers could reasonably be expected to reduce expenditure. PMID- 26845790 TI - Let's get to work. PMID- 26845791 TI - The emotional connection in the patient-caregiver relationship. PMID- 26845792 TI - How to moderate the home dialysis diet. PMID- 26845793 TI - PRESIDENTIAL TIMBER. PMID- 26845794 TI - Transplant community looks for ways to incentivize living organ donation. PMID- 26845795 TI - KDIGO releases living kidney donor guideline for public review. PMID- 26845797 TI - Is the new organ allocation system fair? PMID- 26845796 TI - A level playing field for patient access to transplant. PMID- 26845798 TI - The merits of using a staffing agency. PMID- 26845799 TI - Successful mentoring equals a bright future. PMID- 26845800 TI - CORRELATION OF ORAL HEALTH HOME-CARE PRACTICES, SNACKING HABITS AND DENTAL CARIES EXPERIENCE AMONG HIV-POSITIVE CHILDREN IN NAIROBI, KENYA. AB - OBJECTIVE: To determine the correlation of oral health home-care practices, snacking habits and dental caries experience among 3-15 year-old-HIV-positive children attending out-patient clinic at the Kenyatta National Hospital, Kenya. DESIGN: Cross-sectional descriptive study. SETTING: Kenyatta National Hospital comprehensive care centre out-patient clinic. SUBJECTS: Two hundred and twenty participants were selected by consecutive sampling. The children's socio demographic characteristics and oral health home-care practices were obtained from parent or guardian interviews. Oral examination of the children was carried out to determine the presence of dental caries. RESULTS: Of the 220 children in the study, 126 (57.3%) brushed their teeth at least once a day. Forty one (18.6%) children regularly consumed sweetened snacks daily. Almost all children (75.5%) were taking medication in the form of tablets and capsules. One hundred and seventy nine (81.4%) children had never had a dental visit. The prevalence of dental caries was 65% while the mean dmft and DMFT scores were 1.75 and 1.08 respectively. Caries experience was significantly higher for those children who frequently consumed sweetened snacks and those who took their medication in the form of sweetened syrups while it was lowest in those who brushed their teeth at least twice a day. CONCLUSION: Dental caries experience was significantly higher among HIV-infected children who had increased frequency of consumption of sweetened snacks and those who used syrupy medication. There was poor attendance for dental treatment among the children. PMID- 26845801 TI - DILEMMA OF MANAGING MULTI-SURFACE DENTAL CARIES IN THE PRIMARY DENTITION USING THE ATRAUMATIC RESTORATIVE TREATMENT: RENAISSANCE OR DIMMING HOPE. AB - BACKGROUND: A lot of research work has been carried out to determine the effectiveness of using a traumatic restorative treatment (ART) in the management of dental caries, but there are still unresolved issues surrounding the use of the technique particularly in very large carious lesions. OBJECTIVE: To determine the current survival rates of multi-surface ART restorations placed in the primary dentition and any consequences to the restored tooth after premature loss of the restoration. STUDY SELECTION: Using a set of specific key words, a Pubmed/Medline search was carried out to retrieve all publications on ART restorations placed in primary teeth in the period January 2000 to December 2011. Only publications whose studies had multi-surface ART restorations as an item of study were retrieved and relevant data extracted. DATA SYNTHESIS: Twelve studies contained in 12 publications fulfilled the selection criteria and were included in the study. The selected publications were analysed by the author to establish the study follow-up period and the survival rate of the multi-surface ART restorations for the different follow-up periods. Further information was adduced on any other effects of restoration on the tooth after premature loss of the restoration. RESULTS: The search findings indicated that the survival rate for most of the multi-surface restorations were generally very low. Further, there were indications that even after the premature loss of the ART restorations, most of the affected teeth survived for the period of the study with a number of them having shown no signs of secondary caries or associated dental abscessees. CONCLUSION: While the survival rates of multi-surface ART restorations in the studies documented in the review were low, the ART restorations appeared to provide some beneficial effects to the retention-longevity of the restored tooth even after their premature loss. PMID- 26845802 TI - OUTCOME OF FOAM VERSUS GAUZE DRESSINGS IN NEGATIVE PRESSURE WOUND THERAPY FOR THE MANAGEMENT OF ACUTE TRAUMATIC WOUNDS WITH SOFT TISSUE LOSS AT KENYATTA NATIONAL HOSPITAL. AB - BACKGROUND: Wounds have provided a challenge to the clinicians for centuries and this scenario persists to the 21st century. Negative pressure wound therapy (NPWT) is one of the latest additions in wound management. It has been widely adopted in developed countries with foam as the default wound dressing although it has some limitations. OBJECTIVE: To determine the difference in outcomes between the use of gauze versus foam as wound dressing in NPWT for the management of acute traumatic wounds with soft tissue loss. DESIGN: Prospective randomised comparative interventional study. SETTING: Kenyatta National Hospital Orthopaedic and Surgical wards. SUBJECTS: All patients aged above 12 years with Class III and Class IV acute traumatic wounds. OUTCOME MEASURES: The main outcome measure is the time taken to achieve 100% wound granulation. Comparisons were also made on the mean pain scores during dressing change and the percentage change in wound surface area. RESULTS: Wounds took an average of 8.4 days in the gauze group and 8.1 days in the foam group (p = 0.698) to achieve full granulation. The percentage change in wound surface area was 5.3 versus 5.5 (P = 0.769) in the gauze and foam groups respectively. The infection rates were comparable between the two groups (28% for gauze and 23.1% for foam, p = 0.697) and there was no significant difference in the median pain scores (gauze = 4.5, foam = 4.8 with p = 0.174). However, outcomes with gauze dressing were influenced significantly by the time to application of NPWT, initial wound surface area and wound infection while with foam dressing outcomes tended to be affected less so by the above factors. CONCLUSION: In the use of NPWT for the management of acute traumatic wounds, there is no difference in terms of time to full wound granulation, change in wound surface area, wound infection and pain during dressing change whether gauze or foam is used as the wound dressing material. PMID- 26845803 TI - SURGICAL MANAGEMENT OF BPH IN GHANA: A NEED TO IMPROVE ACCESS TO TRANSURETHRAL RESECTION OF THE PROSTATE. AB - BACKGROUND: Open prostatectomy for benign prostate hyperplasia (BPH) is widely practiced in Ghana and Africa. Some of the reasons include lack of expertise and facilities for Transurethral Resection of the Prostate (TURP) and digital rectal examination assessment of prostates as greater than 50 grams. OBJECTIVES: To assess the prostate volumes of patients for surgical management of BPH by transrectal ultrasound (TRUS) and to determine, on the basis of prostatic volume, what percentage of those who had open prostatectomy could have been managed by TURP. DESIGN: Prospective cohort study. SETTING: The Korle Bu Teaching Hospital, Accra, Ghana. SUBJECTS: Patients for elective surgical management of BPH from March to September 2010 were studied. RESULTS: Fifty-eight. patients had surgical management of BPH. Forty-six of them (79.3%) had open prostatectomy whilst twelve (20.7%) had TURP with a mean age of 70.4 and 65.2 years respectively. The most common reason for the open prostatectomy was refractory retention of urine (76.0%) while that for TURP was lower urinary tract symptoms (58.3%). The mean prostate volume for the patients who had open prostatectomy was 64.2ml +/- 28.7mls (range 23.0-121.0ml) while that of the TURP group was 40.1g +/- 16.2mls (range 18.5-70.0mls). Of the open prostatectomy group, 67.4% of them had prostate volumes 75 mls or less. The blood transfusion and peri-operative complication rates for the open prostatectomy and TURP groups were 13% versus 8.3% and 8.7% versus 8.3% respectively. There was no mortality. CONCLUSION: Access to TURP in the surgical management of BPH in Ghana is low (20.7%). With improved facilities including routine use of TRUS for assessing prostate size and availability of expertise for TURP, 67.4% of patients offered open prostatectomy presently could benefit from TURP, using prostate volumes 75mls (75g) or less as indication for TURP. PMID- 26845804 TI - OESOPHAGEAL CANDIDIASIS IN AN IMMUNOCOMPETENT ADULT, AN ADVERSE EFFECT OF ANTIBIOTIC THERAPY FOLLOWING CARDIAC SURGERY, CASE REPORT AND REVIEW OF LITERATURE. AB - Dysphagia following cardiac surgery is a frequently encountered problem, being most commonly due to the sternotomy incision and/or prolonged intubation. Oesophageal candidiasis is an increasing problem that is usually associated with immunosuppression or immunodeficiency. We report a 59 years age, immunocompetent lady whom had developed dysphagia and odynophagia following open cardiac surgery and long term course of antibiotics. Diagnosis of Candida oesophagitis was established after radiological, endoscopic and microbiological evidence, and successful treatment with combined topical and systemic antifungal therapy was achieved. Possibility of immunodeficiency was excluded. We believe that this lady developed oesophageal candidiasis due to a long-term course of broad spectrum antibiotics. We discuss the various diagnostic modalities and treatment options. PMID- 26845805 TI - FACTORS ASSOCIATED WITH INTERNALISING PROBLEMS IN ORPHANS AND THEIR CAREGIVERS IN RURAL MOZAMBIQUE. AB - OBJECTIVES: To compare internalising problems reported by orphans and their caregivers with that of non-orphans and their caregivers. DESIGN: Case control study. SETTING: Cahora-Bassa District of Tete, Mozambique SUBJECTS: Seventy-six maternal or double orphans (aged 10-14 years) and their caregivers were compared with seventy-four non-orphans and their caregivers living in the same neighbourhood. MAIN OUTCOME MEASURES: children were interviewed with a semi structured questionnaire concerning their internalising problems, family structure, school attendance, daily experiences and perceived problems. The children's primary caregivers were also interviewed concerning their depressive symptoms, available social support, socio-economic conditions and perceived problems. RESULTS: Orphans lived in poorer households than non-orphans and reported more internalising symptoms and more economic and psychosocial disadvantages. Orphan caregivers were more depressed and had less social support than non-orphan caregivers. Child internalising symptoms were independently associated with bullying (B = 8.04, 95% CI: 0.24,15.85), perceived undeserved punishment (B = 11.98, 95% CI: S.98,17.98) and orphan status (B = 33.36, 95% CI: 26.67, 40.05). The effect of punishment was stronger for orphans than non orphans. Frequency of hunger affected internalising symptoms only in orphans. Caregiver depression was independently associated with low social support (B = 0.35, 95% CI: -0.51, -0.18), few possessions (B = -2.10, 95% CI: -3.42, -0.79) an orphan status (B = 4.54, 95% CI: 3.30, 5.78) and possessions had a stronger effect in orphan caregivers. Quality of housing caused depression only in caregivers of orphans. CONCLUSION: Both orphans and their caregivers were more depressed than the non-orphans and their caregivers. They were exposed to more economic and psychosocial disadvantages and were more vulnerable to risks. PMID- 26845806 TI - CRYPTOSPORIDIOSIS AND ITS GENOTYPES AMONG CHILDREN ATTENDING MOI TEACHING AND REFERRAL HOSPITAL IN ELDORET, KENYA. AB - OBJECTIVES: To determine the prevalence of cryptosporidiosis and the associated factors, and characterise the Cryptosporidium isolates from children aged five years and less with diarrhoea. DESIGN: A prospective cross-sectional study. SETTING: This was a health facility and laboratory based study. Screening for Cryptosporidium oocysts was done at the Microbiology laboratory, School of Medicine, Moi University, Eldoret and genotyping and sub-genotyping at the Kenya Medical Research Institute, Nairobi, Kenya. SUBJECTS: Children aged five years and less seen at the outpatient clinic and those admitted in the pediatric wards at MTRH were recruited into the study upon obtaining assent and written consent from the parents or guardians. RESULTS: The prevalence of cryptosporidiosis was 9.8% (N = 317). A duration of diarrhoea of more than two weeks was associated with cryptosporidiosis (OR = 1.8301) compared to those with diarrhoea for less than one week. There were no sex related differences in the cryptosporidiosis prevalence (P = 0.9752). Waste disposal, water sources and treatment, and livestock in homesteads were not associated with cryptosporidiosis. About 82% of the isolates were C. hominis and 18% were C. parvum. There were 6 subtypes of C. hominis and 4 subtypes of C. parvum in circulation. CONCLUSION: The prevalence of cryptosporidiosis is comparable to other regions of the worldwith C. hominis being the most common followed by C. parvum. Human-to-human transmission is the mainmode of spread of cryptosporidiosis. All the Cryptosporidium isolates were from children residing in peri-urban and rural areas. PMID- 26845807 TI - TYPES OF ALBINISM IN THE BLACK SOUTHERN AFRICA POPULATION. AB - BACKGROUND: Oculocutaneous albinism (OCA) is the most common inherited disorder in Southern African blacks and several types have been described. Molecular techniques, where available, can be used to confirm a clinical diagnosis and the type of OCA, if necessary, and for prenatal diagnosis. OBJECTIVES: To investigate and classify the different types of albinism commonly found and to determine the clinical implications for each type. DESIGN: A descriptive survey. SETTING: Gauteng province, South Africa, and Lesotho. SUBJECTS: Three groups of subjects with OCA (96 from a genetics clinic, 62 from a dermatology clinic, and 31 from community surveys) from the black African population participated. MAIN OUTCOME MEASURES: Subjects underwent clinical and/or dermatological examinations and were then classified according to type of OCA. RESULTS: Four forms of OCA were identified: most (82%) subjects had OCA2 (a tyrosinase- positive type) with three sub-types: those without large freckles (ephelides) on exposed areas (named OCA 2a in this study), those with such freckles (named OCA 2b), and those with brown albinism (BOCA); the remainder had red/rufous albinism, ROCA (OCA 3). The four forms could be distinguished from each other clinically without using molecular genetic testing. CONCLUSION: The most common types of albinism found in the black population of Southern Africa are OCA2 and OCA3. Given the high prevalence of the disorder, together with the high risk of skin cancer, and the recent persecution of affected individuals in certain East African countries, these findings and their clinical implications have significance in terms of both education and awareness for health professionals and lay people caring for those with albinism. PMID- 26845808 TI - BRUCELLOSIS IN TEREKEKA COUNTY, CENTRAL EQUATORIA STATE, SOUTHERN SUDAN. AB - OBJECTIVES: To identify factors associated with Brucellosis in patients attending Terekeka Health Facility, Terekeka County, Central Equatoria State, Southern Sudan and to evaluate the utility of the rapid test kit Euracil(r). DESIGN: A facility based case-control study. SETTING: Terekeka Health Facility, Terekeka County, Central Equatoria State, Southern Sudan. SUBJECTS: Cases were patients presenting at the Terekeka Health Facility with clinical symptoms suggestive of Brucellosis and tested positive for Brucellosis by rapid antigen test while controls were selected from individuals attending Terekeka Health facility with health problems unrelated to brucellosis or febrile illness. RESULTS: A total of fifty eight cases with clinical symptoms suggestive of and tested positive for Brucellosis by rapid antigen test presented. A total of 116 consented controls were recruited into the study. Males accounted for 52% of the cases and 53% of the controls. The mean age was 31 years for both groups. Cases without formal education were 84% while 40% had no source of income, 20% of the cases and 14% of the controls were cattle keepers while 5% of the cases and 13% of the controls were students. In multivariate analysis there were many factors associated with Brucellosis like consumption of raw meat, living with animals at the same place, raising of goats, farm cleaning contact, eating of aborted and wild animals. Logistic regression revealed two factors associated with the disease; consumption of raw milk (OR=3.9, P-value 0.001, 95% CI 1.6666-9.0700) was a risk factor while drinking boiled milk was protective (OR = 0.09, p-value 0.000, 95% CI, 0.1-0.2). CONCLUSIONS: The main age-groups affected were 20-30 years with males being affected more than females. Drinking of raw milk was significantly associated with Brucellosis while drinking boiled milk was protective. There should be active public health education on the benefits of boiling milk before consumption. Further studies to elucidate the extent and epidemiology of brucellosis in humans and animals in Southern Sudan are recommended. PMID- 26845809 TI - GIANT SOLITARY NEUROFIBROMA IN THE GLUTEAL AREA OF A PATIENT WITHOUT NEUROFIBROMATOSIS. AB - Neurofibromas are benign tumours arising from neurons andperineural cells. Although they are common inneurofibromatosis, occasionally solitary neurofibromas may occur. A rare case of solitary neurofibroma presenting as a giant gluteal mass in a male patient without a personal or family history of neurofibromatosis is presented. Pre-operative imaging gave useful information about the extent of the mass which was then totally excised with histology revealing a non-plexiform neurofibroma. Distinguishing between isolated neurofibromas and those associated with neurofibromatosis is important because the treatment and prognosis differ greatly with the former having a good prognosis after total excision. PMID- 26845810 TI - MALOCCLUSION AND ORTHODONTIC TREATMENT NEED AMONG 12-15-YEAR-OLD CHILDREN IN NAIROBI. AB - OBJECTIVE: To describe the pattern of occurrence of malocclusion and orthodontic treatment need. DESIGN: A descriptive cross-sectional survey. SETTING: Six public primary schools in Nairobi, Kenya. SUBJECTS: A randomly selected sample of 1382 children aged 12 to 15 years. Clinical examination for malocclusion was conducted using the Dental Aesthetic Index (DAI). Orthodontic treatment need was derived using the regression equation stated in the DAI. RESULTS: Among the 1382 (672 males and 710 females) children examined, 70 children (5.1%) had missing teeth. Crowding and spacing in the incisal segments occurred in 652 (47.2%) and 644 (46.6%) children respectively. Anterior irregularities were found in 533 (38.6%) of the subjects in the maxilla and 430 (31.1%) in the mandible. Anterior crossbite was found in 86 (6.2%) of the children. The anterior open-bite occurred in 194 (14%) of the children with significantly more open-bite in females than males (p=0007). The maxillary median diastema and antero -posterior molar relation discrepancies were found in 289 (20.2%) and 344 (24.9%) of the sample respectively. The sample mean DAI score was 26.6 (SD 7.8). Seven hundred and thirty two (53.0%) of the children examined had either no need or slight need for treatment whereas 650 (47%) were found with orthodontic treatment needs ranging from elective 318 (23%), highly desireable 176 (12.7%) to mandatory 156 (11.3%). CONCLUSION: There was an overall high prevalence of malocclusion with 11.3% of the sample exhibiting handicapping malocclusion. Notably, there were no significant gender differences for most of the traits except for anterior open bite which was found to occur more in females than males. PMID- 26845811 TI - GLOMERULAR FILTRATION RATE PROFILES IN PAEDIATRIC PATIENTS ON CANCER CHEMOTHERAPY AT THE KENYATTA NATIONAL HOSPITAL, KENYA. AB - BACKGROUND: An accurate estimation of renal function in children is important in optimising the dose of many drugs used in paediatric oncology for allowing clinical monitoring of the nephrotoxic effects of cytotoxic agents such as cisplatin. The glomerular filtration rate (GFR) is widely accepted as the best index of renal function in patients. Chemotherapy is the mainstay of treatment in the paediatric oncology unit at the Kenyatta National Hospital. OBJECTIVES: To determine the glomerular filtration rate profiles of paediatric oncology patients and to assess changes that had occured over a period of at least six months of continuing cancer chemotherapy. DESIGN: Cross-sectional hospital based survey. SETTING: General Paediatric wards, including Paediatric Oncology and Paediatric Ophthalmology ward. Kenyatta National Hospital, Nairobi, Kenya. Subjects: Paediatric patients who had an established diagnosis of cancer and had been on chemotherapy for at least six months. RESULTS: Out of the 115 children enrolledin the study 43 had abnormal kidney function, This gave a prevalence of 37% (95% CI 28-46).The other 72 children had normal kidney function. Patients aged less than five years and those with solid tumors had a higher likelihood of having an abnormal GFR compared to their older counterparts and thosc with-lymphomas and leukemias. CONCLUSIONS: Monitoring of GFR should be done regularly as decline occurs as one continues on chemotherapy especially for the ones below five years and those witl solid malignancies. PMID- 26845812 TI - IMPACT OF PARTIAL KANGAROO MOTHER CARE ON GROWTH RATES AND DURATION OF HOSPITAL STAY OF LOW BIRTH WEIGHT INFANTS AT THE KENYATTA NATIONAL HOSPITAL, NAIROBI. AB - OBJECTIVE: To determine the effect of partial Kangaroo Mother Care (KMC) on growth rates and duration of hospital stay of Low Birth Weight (LBW) infants. DESIGN: Unblinded, randomised clinical controlled trial. SETTING: Kenyatta National Hospital, Nairobi, Kenya. SUBJECTS: Over a nine month period, consecutive recruitment of eligible LBW infants weighing 1000 g to 1750 g was done until a sample of 166 infants was reached. INTERVENTION: Kangaroo mother care was practised over an eight hour period per day for the intervention group while the controls remained in incubators or cots. Weight, head circumference, and mid upper arm circumference were monitored for all infants till discharge at 1800 g. RESULTS: Of the 166 infants recruited 157 were followed up to discharge. Baseline characteristics were similar for the two groups except for mother's age, with the KMC group mothers having a mean age of 26.5 years while the control group mothers had a mean age of 24 years, (p = 0.04). The KMC group had significantly higher growth rates as shown by the higher mean weight gain of 22.5 g/kg/day compared with 16.7g/kg/day for the control group, (p < 0.001); higher mean head circumference gain of 0.91 cm/week compared with 0.54 cm/week for the control group, (p < 0.001) and higher mean mid upper arm circumference gain of 0.76 cm/week compared with 0.48 cm/week for the control group, (p = 0.002). Although overall duration of stay was similar between study arms, when infants were stratified into those above or below 1500 g KMC infants' duration of stay was significantly shorter than those in regular care. Using logistic regression, KMCwas the strongest predictor formeanweight, meanhead circumference and mean MUAC gain while mother's age (older) was the strongest predictor for mean duration of stay with KMC being an independent predictor of duration of stay. CONCLUSION: Low birth weight infants in this cohort achieved rates of growth within the recommended intrauterine growth but babies managed using partial KMC grew faster and were thus discharged earlier than those on standard of care. Since partial KMC was beneficial, it should be fully implemented for all eligible infants. PMID- 26845813 TI - AN APPRAISAL OF RABIES OCCURRENCE AND CONTROL IN KISUMU MUNICIPALITY, KENYA. AB - BACKGROUND: Rabies is a serious neglected disease which occurs worldwide. In urban areas, the control of the diseaseis expected to be hampered by several unique constraints. OBJECTIVE: To appraise the occurrence and control of rabies. STUDY DESIGN: The tools used in the study included key informant interviews with senior veterinary and medical officers and a questionnaire survey on 15 veterinary officers and 9 human physicians. The occurrence of animal bites and costs involved in treatment was also investigated using retrospective hospital data for the year 2007. SETTING: Kisumu Municipality, Kenya. RESULTS: The control of rabies was under the Veterinary Department through dog vaccinations and baiting, and also under the Department of Public Health (DPH) through people vaccinations and post exposure treatments. The constraints observed were poor coordination in rabies control efforts, understaffing and limited resources. Animal bites were common with 1270 cases reported during 2007. The post-bite rabies vaccines were mainly purchased from local chemists at KES 7,500 per full dose. This amounted to an annual total cost of KES 9,525,000 (136,071 USD). The bites were mainly from domestic dogs (89%) and occurred commonly in highly populated areas. The mean age of people with bites was 21 (2.5 - 78) years, showing that young people had a higher risk. Males (59%) were at higher risk of bites than females (41%). CONCLUSIONS: It would be important for the relevant departments to harmonise their rabies control strategies and also address the prevalent constraints by using local networks. The incidence of rabies and the associated epidemiology needs proper updated documentation with a view of carrying out mass vaccination of dogs at times free of cost to the economically disadvantaged owners. PMID- 26845814 TI - PSYCHIATRIC MORBIDITY IN A NIGERIAN NEUROLOGY CLINIC. AB - OBJECTIVE: The objective of the study was to determine the prevalence and nature of psychiatric morbidity among patients attending a neurology outpatient clinic. DESIGN: A two-stage screening procedure with General Health Questionnaire (GHQ 12) and Schedules for Clinical Assessment in Neuropsychiatry (SCAN) was used to assess psychological disorders over a one year period. Psychiatric diagnosis was based on ICD-10 criteria. SETTING: University of Ilorin Teaching Hospital (UITH), Ilorin-Nigeria SUBJECTS: Two hundred and thirty-five (235) patients aged 18 years and above attending the neurology outpatient clinic. RESULTS: Overall prevalence of psychiatric morbidity was 26.0% (61/235). The most frequent diagnoses were depression (14.9%), generalised anxiety disorder (5.5%), dementia (2.6%) and substance use disorder (1.3%). Significantly more patients with stroke had psychiatric morbidity. CONCLUSION: The study supports previous reports that psychiatric disorders are quite common among patients with neurological disorders. Efforts should, therefore, be directed at identifying and treating neurological patients with psychiatric morbidity since this will ensure improved outcome. In this regard, mental health professionals would need to provide liaison services for the neurologists and train them in the use of simple screening instruments for detecting associated psychiatric disorders with appropriate referral where necessary. PMID- 26845816 TI - They Trust Us, But Do They Know Us? PMID- 26845815 TI - CENTRAL NERVOUS SYSTEM LIGNOCAINE TOXICITY IN AN INFANT FOLLOWING VENTRICULO PERITONEAL SHUNT AND SPINA BIFIDA REPAIR: A CASE REPORT. AB - A 3.7 kg one-month-old male infant with Spina Bifida Cystica with Hydrocephalus had Ventriculo-Peritoneal (VP) Shunting and repair of the Spina Bifida Cystica done. Lignocaine with Adrenaline 1:100,000 was infiltrated intra-operatively to reduce blood loss. Overenthusiastic infiltration, an oversight, led to Lignocaine toxicity. In Pediatrics, prior calculation of maximum dosage, based on child's weight, and use of dilute solutions for multiple sites could have prevented this. PMID- 26845817 TI - Nurse Practitioner Care Model: Meeting the Health Care Challenges With a Collaborative Team. AB - In today's environment, organizational delivery systems must produce high quality, efficient, and cost-effective services. Central to restructuring care delivery is the evolving role of the nurse practitioner (NP) and the integration of the role as part of the health care workforce. The NP Care Model was designed and introduced to the organizational workforce in a medical center to coordinate, manage, and monitor the outcomes of high-risk patients with chronic disease efficiently. This program focused specifically on patients with heart failure who were discharged to home and identified to be at high-risk for early readmissions. The Healthy Heart Initiative prograrr coordinated by the NP addressed targeted causes of rehospitalization (lifestyle, medication and diet noncompliance, and lack of self-care disease management). The program objective of improved financial performance were met by reducing the 30-day readmission rate. Operational effectiveness and quality patient outcomes were met through the design and implementa tion of the NP Care Model, and overall patient reported satisfaction. PMID- 26845819 TI - Successful Shared Governance Through Education. AB - Shared governance is one way nurses can attain a healthy work environment. Having direct-care nurses involved in raising relevant clinical and operational issues and creating systematic approaches has been linked to greater levels of empowerment which is often transposed into shared governance. Nurse leaders at one hospital used a comprehensive educational strategy to implement shared governance in less than 2 years. An authoritative style of leadership and decision making does not meet the needs of today's complex health care environment; nor does it meet the needs of today's employees. The focus on a very deliberate and educational strategy for shared governance was successful in building the structures and processes needed to take a unit and division from traditional governance to shared governance in less than 2 years. PMID- 26845818 TI - Comparing Aging in Place to Home Health Care: Impact of Nurse Care Coordination On Utilization and Costs. AB - The goal of this study was to compare utilization and cost outcomes of patients who received long-term care coordination in an Aging in Place program to patients who received care coordination as a routine service in home health care. This research offered the unique opportunity to compare two groups of patients who received services from a single home health care agency, using the same electronic health record, to identify the impact of long-term and routine care coordination on utilization and costs to Medicare and Medicaid programs. This study supports that long-term care coordination supplied by nurses outside of a primary medical home can positively influence functional, cognitive, and health care utilization for frail older people. The care coordinators in this study practiced nursing by routinely assessing and educating patients and families, assuring adequate service delivery, and communicating with the multidisciplinary health care team. Care coordination managed by registered nurses can influence utilization and cost outcomes, and impact health and functional abilities. PMID- 26845820 TI - Chasing Zero: A Nurse-Driven Process For Catheter-Associated Urinary Tract Infection Reduction in a Community Hospital. AB - Due to treatment costs and lack of reimbursement, community hospitals are charged with implementing innovative strategies that will reduce the incidence of hospital-acquired catheter-associated urinary tract infections (CAUTI). A nurse driven system for decreasing the number of hospital-acquired CAUTI is effective and useful for a community hospital. One nurse with accountability for implementing a simple evidence-based protocol can dramatically decrease the total incidence of hospital-acquired CAUTI. The basis for the success of this initiative relied heavily on the ease of using the eight-point Question the Foley criteria, the availability of the electronic medical record, interdisciplinary collaboration, and support from nursing and physician administration. With collaboration and support from nursing leadership, the goals for patient safety by reducing hospital-acquired CAUTI can become a reality in a short period of time. PMID- 26845821 TI - Patient Engagement in Hospital Fall Prevention. AB - Injurious falls are the most prevalent in-hospital adverse event, and hospitalized patients are at a greater risk of falling than the general population. Patient engagement in hospital fall prevention could be a possible approach to reducing falls and fall-related injuries. To engage patients, bedside nursing staff must first understand the concept of patient centeredness and then incorporate patient centeredness in clinical practice. Clinicians should move from being experts to being enablers. To conceptualize the knowledge gaps identified, a conceptual model was developed to guide future research and quality improvement efforts in hospital settings. This model could be used as a guide to advance nursing leadership in hospital fall prevention via promoting patient engagement (e.g., developing patient-centered fall prevention interventions with patients' input). PMID- 26845822 TI - California Collaborative Model For Nursing Education: Building A Higher-Educated Nursing Workforce. AB - The California Collaborative Model for Nursing Education (CCMNE) promotes seamless ADN-BSN academic progression as the most effective means by which the state can educate the numbers of BSN-prepared nurses needed in the future. Accelerated by state legislation and a national commitment to a higher-educated nursing workforce, the framework is sufficiently flexible to accommodate a variety of strategies that meet the intent of each Core Component, and can be implemented at local, regional, or state levels. Six percent of all current ADN students in California are dual enrolled in CCMNE BSN programs. CCMNE has a positive effect on ADN-BSN completions and will support increasing nursing workforce diversity in California. PMID- 26845823 TI - Intelligently Managed Data: Achieving Excellence In Nursing Care. AB - Much information and clinical data are available in health care. Unfortunately, much of it is not available for clinical decision making and management support. Analytics within the context of health information technology (HIT) will provide a framework to bring better reasoning and intelligence to HIT and nursing care. The missing link is the people who will bring this forward into the everyday lives of clinical nurses and nurse executives. With better competencies among staff and leaders in nursing and more credentialed nursing informatics leaders in influential positions, nursing will be a full participant in the digital revolution which, along with analytics, will lead to intelligent and effective systems. PMID- 26845824 TI - Oral and Maxillofacial Pathology. Case of Month. Keratitic Psoriasiform Mucositis. PMID- 26845825 TI - CAT OF THE MONTH. Critically Appraised Topics. The Cardiovascular Health Benefits of Oral Appliance Therapy for Obstructive Sleep Apnea Typically Outweigh the Risk of Tooth Movement and Malocclusion (UT CAT #2808). PMID- 26845826 TI - The 2015 Gold Medal for Distinguished Service--DR MICHAEL L. STUART. PMID- 26845827 TI - Comparison of shear bond strength of self-etch and self-adhesive cements bonded to lithium disilicate, enamel and dentin. AB - Comparison of shear bond strength of self-etch and self-adhesive cements bonded to lithium disilicate, enamel and dentin. AIMS: With several self-adhesive resin cements currently available, there is confusion about which product and technique is optimal for bonding ceramic restorations to teeth. The objective of this study was to compare the shear bond strength of lithium disilicate cemented to enamel and dentin using 5 adhesive cements. MATERIALS AND METHODS: 100 lithium disilicate rods were pretreated with 5% hydrofluoric acid, silane, and cemented to 50 enamel and 50 dentin surfaces using five test cements: Variolink II (etch and-rinse) control group, Clearfil Esthetic (two step self-etch), RelyX Unicem, SpeedCEM, and BifixSE (self-adhesive). All specimens were stored (37 degrees C, 100% humidity) for 24 hours before testing their shear bond strength using a universal testing machine (Instron). Debonded surfaces were observed under a low power microscope to assess the location and type of failure. RESULTS: The highest bond strength for both enamel and dentin were recorded for Variolink II, 15.1MPa and 20.4MPa respectively, and the lowest were recorded for BifixSE, 0.6MPa and 0.9MPa respectively. Generally, higher bond strengths were found for dentin (7.4MPa) than enamel (5.3MPa). Tukey's post hoc test showed no significant difference between Clearfil Esthetic and SpeedCem (p = 0.059), Unicem and SpeedCem (p = 0.88), and Unicem and BifixSE (p = 0.092). All cements bonded better to lithium disilicate than to enamel or dentin, as all bond failures occurred at the tooth/adhesive interface except for Variolink II. CONCLUSIONS: Bond strengths recorded for self-adhesive cements were very low compared to the control "etch and rinse" and self-etch systems. Further improvements are apparently needed in self-adhesive cements for them to replace multistep adhesive systems. CLINICAL IMPLICATIONS: The use of conventional etch and rinse cements such as Veriolink II should be preferred for cementing all ceramic restorations over self-adhesive cements until the bond strengths are improved. PMID- 26845828 TI - Permission Marketing: WHAT IT IS AND WHY IT'S BETTER (THAN THE OTHER KIND OF MARKETING). PMID- 26845830 TI - THE FRONT LINES OF PATIENT SAFETY. Multilevel efforts improve the care environment. PMID- 26845829 TI - Ensuring safe hospitals through interior design. PMID- 26845831 TI - Creating a culture of safety. Facilities professionals play bigger role in maintaining patient welfare. PMID- 26845832 TI - Building a safe environment. Health care designers prioritize patient safety while crews limit construction effects. PMID- 26845833 TI - Bundle up to fight infections. Patients safety efforts widen to help hospitals combat antibiotic-resistant bacteria. PMID- 26845834 TI - Infrastructures to improve safety. Technology and engineering systems help to boost environment of care. PMID- 26845835 TI - Linking patient safety and the supply chain. Health care systems are integrating new patient-centered processes into delivery. PMID- 26845836 TI - Improving patient satisfaction through front-line leaders. PMID- 26845837 TI - Design standards for imaging spaces. Complying with new Joint Commission safety requirements. PMID- 26845838 TI - [BRAIN FOCAL ISCHEMIA-REPERFUSION CAUSES A DECREASED RESISTANCE OF ERYTHROCYTES FROM VENOUS BLOOD TO ACID HEMOLYSIS, WHICH IS PREVENTED BY ECDYSTERONE]. AB - We investigated the resistance of erythrocytes from rat brain venous blood to acid hemolysis in the dynamics of brain ischemic period (15, 30, 45 and 60 min), as well as in the early (5 min) and distant (24h) period of brain reperfusion. Brain ischemia-reperfusion was made in rats that received ecdysterone (standartized extract of Serratula coronata) within 18 days (per os, 1 mg/kg). Analysis of the kinetic curves of acid hemolysis showed a pronounced (60 times, from 1.45 to 85.85% at 60 min of brain ischemia and at 5 min of brain reperfusion, respectively) increase of unstable erythrocytes that hemolyzed easily (< 2.5 min). In the preconditioned rats, this increase was only 8-fold. During the period of brain ischemia, with a maximum at 15th minute, in the venous blood from brain the diene conjugates (DK) pools increased from 2.40 to 9.48 ng/mg protein and LTC4 pools increased from 1.49 to 5.98 pmol/mg protein. Even more pools of DC and LTC4 were increased at 5th min of brain reperfusion. In animals received ecdysterone, during ischemia and early reperfusion period, both pools of DC and LTC4 in venous blood were lower than that in the controls. The latter implies a possible antiradical mechanism of the protective effect of ecdysterone. PMID- 26845839 TI - Proteasomal activity in brain tissue following ischemic stroke in Wistar rats. AB - Functional as well as structural reorganization of brain tissues takes place in the surrounding and remotes brain areas after focal ischemic lesions. In particular, reactive or regenerative processes have been described to occur in the infarction areas and the contralateral hemisphere. Experiments were performed on 63 rats, divided into 3 groups (each consisted of 21 animals): sham operated, short-term occlusion of the right middle cerebral artery (MCAO) group, and long term MCAO group. We have studied changes in proteasome proteolysis during transient occlusion of the middle cerebral artery using method of Koizumi J., duration 2 and 60 min and made the comparison between changes in different types of proteasome activity and severity of ischemic injury and showed three types of decrease inproteolytic activity (trypsin-, chymotrypsin-like, peptidylglutamyl peptide-hydrolyzing) in the brain tissues. Chymotrypsin-like activity of ischemic areas of the brain for short-term MCAO decreased 4.1 times compared with controls (P > 0.05), for long-term MCAO decreased 5.8 times compared with controls (P < 0.05). Trypsin-like activity of ischemic areas of brain for short-term MCAO decreased 7.1 times compared with controls (P > 0.05), for long-term MCAO decreased 12.5 times compared with controls (P < 0.05). PGPH activity of ischemic areas for short-term MCAO decreased 8 times compared with controls (P > 0.05), for long-term MCAO decreased 2.8 times compared with controls (P < 0.05). The similar dynamics was observed also in the penumbra and the core zone of the brain at 6 h of reperfusion, in the long run there is no significant difference between the core and contralateral zones. Our results suggest that proteasome activity may play also a role in contralateral cortical plasticity occurring after focal cerebral ischemia. PMID- 26845840 TI - Influence of single nucleotide polymorphisms of vitamin D receptor-gene on the level of osteoassociated hormones linkage with postmenopausal osteoporosis. AB - The levels of osteoassociated hormones, macroelements, interleukines, cyclic nucleotides and activity of alkaline phosphatase were being detected in the blood plasma of 74 postmenopausal women with and without osteoporosis (OP). Bone mineral density (BMD) and the metacarpal index were being assessed according to the results of densitometry. The allele polymorphisms vitamin D receptor gene (VDR) Cdx2 (rs11568820) and TaqI (rs731236) were being identified with the help of the polymerase chain reaction. The major genotype CC TaqI was found in the group without OP 3.4 times more often than with OP, while the minor genotype TT was found 3.4 times more often with the presence of OP. The presence of the genotype CC TaqI decreased the risk of OP progress by 5.5 times, and the genotype TT TaqI increased by 5.4 times. The presence of the minor allele T was associated with the higher levels of interleukin 1beta, BMD and lower testosterone blood level. The major homozygote AA Cdx2 was found in women without OP 2.9 times more often, while the minor genotype GG - 5.4 times more often with the presence of OP. The presence of the major homozygote decreased the risk of OP progress by more than 5.3 times, while the minor homozygote increased the risk by 8 times. The presence of the minor allele G in the genotype was associated with the increase of parathyroid hormone, phosphorus, magnesium, alkaline phosphatase activity in blood, BMD and with the decrease of testosterone, progesterone and calcium blood levels. PMID- 26845841 TI - [BIOELECTRIC ACTIVITY OF INTERNEURONES OF SPINAL CORD IN THE EXPERIMENTAL MENOPAUSE IN FEMAL RATS]. AB - We analyzed the amplitude-time characteristics of the components of the potential dorsal surface of the spinal cord (PDS SC) in experimental menopause. The excitation threshold increased at 102.14% and the latent period at 94.12% in animals with experimental menopause. In the context of supramaximal stimulation of dorsal root L5 identified N1 amplitude growth at 10.14%, N2 at 11.82%, N3 at 48.28%, and P-wave 31.58% and to increase component N3 26.54% in the experimental group. At condition of paired stimulation pulses on the time interval from 2 to 3 ms there was a significant increase, and from 6 to 30 ms--a depression of N1 component of the second PDS SC in the group of animals with experimental menopause. Thus, our results suggest the presence of changes in nerve structures of the posterior horn of the spinal cord at conditions of estrogen deficiency. PMID- 26845842 TI - [THYMIC HORMONES, ANTIOXIDANT ENZYMES AND NEUROGENESIS OF BULBUS OLFACTORIUS IN RATS WITH PARKINSONISM: THE EFFECT OF MELATONIN]. AB - The adult rats received both neurotoxin 6-hidroxidophamine and neurotoxin and melatonin. It was investigated a link between the disturbances of the brain antioxidant enzymes activity and thymic endocrine function, as possible pathogenic factors of parkinsonism, with changes in the number of neural stem cells (NSC) in the bulbus olfactorius. Rats with motor asymmetry in the apomorphine test and significant damage of the dopaminergic neurons in the substantia nigra have decreased levels of superoxide dismutase, catalase and glutathione peroxidase activities in striatum (1.3-1.4 times) and blood thymulin content (8 times) compared to control group. On the contrary, examined indices were not changed in rats without motor asymmetry and correspondingly partly damaged neurons. The number of nestin(+)-cells in the bulbus olfactorius of rats without motor asymmetry increased from 91.2% to 99.3% and remained unchanged after melatonin administration course (10 mg/kg during 18 days). Melatonin administration resulted in the decrease in the number of nestin(+)-cells along with significant elevation of the decreased antioxidant enzymes activity and blood thymulin content in rats with circulatory movements. Possibilities of the enhancement of NSC differentiation in bulbus olfactorius into neuronal direction in such animals has been discussed. The conclusion about the potential use of melatonin as a neuroprotector in parkinsonism therapy has been made. PMID- 26845843 TI - [MORPHOFUNCTIONAL STATE OF THE THYROID GLAND AFTER EXPOSURE TO MELATONIN]. AB - Morphofunctional state of the thyroid gland (TG) of young rats after exposure of exogenous melatonin in the spring and autumn periods was investigated. Exogenous melatonin (Unipharm Inc., USA) was administered to experimental group of animals daily at a dose 5 mg/kg. The duration of the experiment was 28 days. It was shown an increase of the cross-section area of follicles by 31% and colloid by 30% (in spring), reduction of the area of follicle epithelium by 12% (in autumn), an increase in the follicle internal diameter and a decline in the thyroid epithelium height by 12% (in autumn) in TG of experimental groups rats. Also it was shown a decline of follicle-colloid index and growth of colloid accumulation index, reduction amount of interfollicular islets. The introduction of melatonin in the spring period brought down the amount of connecting tissue elements. Melatonin introduction in the autumn period reduced the thickness of connective tissue trabecules in TG. The introduction of melatonin in the spring period resulted in more substantial changes in the structure of TG, as compared to an autumn experiment. Thus, melatonin administered both in the spring and in the autumn periods reduces the functional activity and physiological regeneration of TG. PMID- 26845844 TI - [THE ROLE OF NO AND MEXIDOL IN CONTRACTILITY OF OVARIAN AND CERVICAL PARTS OF UTERUS UNDER THE CONDITION OF IMMUNE-MEDIATED INJURY IN MICE]. AB - Contractility of ovarian (OP) and cervical parts (CP) of uterus under the condition of immune-mediated injury which was induced by immunization with bovine serum albumin (BSA) was investigated. It was shown that under the activation of energy-synthesizing function of mitochondria with Mexidol the frequency of reductions in both uterine parts decreased, the amplitude and contractility index in the OP and CP as well as the duration of the active state in CP increased. Mexidol under the condition of immunization with BSA leads to the decrease in amplitude in 2,6 time and contractility index in 2,2 time in OP and to the increase of them in CP. It was shown that contractility features of ovarian and cervical parts of uterine under the condition of BSA- induced immunization were caused by changes of mitochondria functional state and were associated with nitric oxide. PMID- 26845845 TI - Expression of aryl hydrocarbon receptor and ATG16L1 protein in experimental oxazolone-induced colitis in rats. AB - We studied the expression of AhR and ATG16L1 protein in experimental oxazolone induced colitis in rats and anti-inflammatory action of recombinant antagonist of IL-1 receptors (ARIL-1) and simvastatin. The immunopositive cells were determined using an indirect immunofluorescence technique with using a monoclonal rat antibody. It has been established that development of colitis was accompanied by an increase of total number of ATG16L1-lymphocytes (by 30%, P < 0.05) in lymphoid structures of the colon. However the amount of AhR(+)-lymphocytes has not changed. At the same time has increased the concentration of ATG16L1 protein (by 4-11%, P < 0.05) in immunopositive cells. Administration of simvastatin and ARIL 1 during the development of experimental pathology was accompanied by decrease of total number of AhR(+) (by 24-38%, P < 0.05) and ATG16L1(+)-lymphocytes (by 43% - 2 fold, P < 0.05) in the colon. PMID- 26845846 TI - [DYNAMICS OF GLUTAMINE SYNTHASE ACTIVITY IN RAT BRAIN IN PRENATAL HYPOXIA MODEL]. AB - Prenatal ontogenesis is a period of high sensitivity to stressful impact, so any stressor can lead to changes of physiological, biochemical indicators, behavioral and cognitive functions. The most common and clinically significant stress factor, which the embryo may be exposed during embryonic development, is hypoxia. In this case pathological changes in the central nervous system depend on the duration and severity of hypoxic exposure, individual tolerance and the stage of prenatal development, at each of which in the brain take place the basic histogenetic processes. By activating energetically disadvantageous anaerobic glycolysis hypoxia leads to excess of glutamate emission and cell apoptosis. Glutamine synthase is a basic enzyme that regulates metabolism of glutamate, catalyzing conversion of glutamate to glutamine with ammonia detoxification. The aim of the presented work was to reveal changes in the activity of one of the key enzyme of glutamate metabolism- glutamine synthetase in the brain of offspring of white rats undergone to hypoxia at different stages of prenatal ontogenesis. Hypoxia was created by placing female rats at stages of the pregnancy, corresponding to progestation period of organogenesis and fetal period of prenatal development, in the hypobaric chamber with exposure to 5% oxygen and 95% nitrogen gas mixture during 30 minutes per day. The offspring obtained from females of control and experimental groups were used for biochemical determinations in the age of 1 and 3 month. It has been established that hypoxia exposed to pregnant females during embryonic organogenesis causes significant changes in enzyme activity, particularly pronounced in the cerebral cortex and cerebellum, as compared with progestational and fetal hypoxia. Enzyme activity decreased in a greater degree in one-month-old rats undergone to prenatal hypoxia, than three- month-old animals. Thus, stress during intensive processes of proliferation and migration of cells of the forming brain violates glutamate metabolism of the brain. PMID- 26845847 TI - [FUNCTIONING PROTEASES IN THE ESOPHAGUS MUCOSA AFTER CHEMICAL BURNS]. AB - The main result of esophagus burn is the formation of scars, that caused by excessive synthesis of collagen and changes the balance of metalloproteinases and their tissue inhibitors. It was studied the activity of proteolytic enzymes, participation of MMP (metalloproteinase) and their tissue inhibitors (TIMP) in alkali burns of the esophagus 1st and 2nd degrees. We have shown a significant increase of TIMP level in homogenate after alkali burns of the esophagus (an average of 31-56% depend on of burn degree). We observed a reduced activity of serine proteinase after 1st degree burns on 15th, 21st day 35 and 18% respectively, after burns 2nd degree on 15th, 21st day 54 and 50%. The decrease of activity MMP after 1st degree burns on 15th and 21st day 30, 19%, respectively, in conditions of chemical burns 2nd degree on 15th and 21st day 30, 37%. These data may indicate the development of scarring after burn simulation of 2nd degree. Further investigation of the MMP and TIMP in the process of wound healing can be useful in creating effective approaches to prevent formation of post scarring of the esophagus. PMID- 26845848 TI - [INFLUENCE OF INTERMITTENT NORMOBARIC HYPOXIA ON THE VEGETATIVE HOMEOSTASIS IN CHILDREN FROM RADIOECOLOGICALLY AFFECTED REGIONS]. AB - The effect of intermittent normobaric hypoxia (INH) of sanogenic level on children living in radioactively contaminated territories has been investigated. Children divided into three groups: 37 patients were included in the main group (the 1st group--medical therapy according to the protocols and INH sessions), 35 persons--in the comparison group (the 2nd group--medical therapy), 30 persons--in the control group (the 3rd group--healthy persons). A significant increase in RMSSD index by 36% in phone registration was established in children aged 6-11 years of the main group after combined treatment with INH sessions (10-12% oxygen in nitrogen), and by 27% under the use of orthoclinostatic test in children aged 12-17 years. A decrease of the sympathovagal index by 23% in children aged 6-11 years was demonstrated concerning the group of comparison. The tension index of regulatory systems was decreased in children of both groups, that is indicative of the decrease in the central contour of cardiac rhythm control. PMID- 26845849 TI - [DOXORUBICIN-INDUCED ALTERATIONS IN PRO-AND ANTIOXIDANT BALANCE AND THEIR CORRECTION BY CURCUMIN IN THE NEONATAL RAT CARDIOMYOCYTES CULTURE]. AB - It was studied the effect of doxorubicin on the HIF system and the pro antioxidant balance of neonatal cardiomyocytes as well as the possibility of the oxidative stress correcting using curcumin. It has been revealed that the expression of mRNA HIF-1alpha using doxorubicin at a dose of 0.5 MUM was 2.9 +/- 0.8 cu, so it decreased by 20% compared to control--3.6 +/- 0.7 cu (P < 0.05). The level of expression of the HIF target gene PDK-1 also significantly decreased (4 times). During the incubation with doxorubicin, the number of live cells decreased by 50.4% relative to control. And after using doxorubicin and curcumin together, the percentage of dead cells decreased by 7,7 compared to doxorubicin only. Doxorubicin intoxication led to a significant increase in the secondary products of lipid peroxidation (TBARS) in cardiomyocytes by 3.6 times and hydrogen peroxide by 64%. Prolonged incubation with doxorubicin reduced the enzymatic activity of Mn-SOD by 32%, while catalase activity increased by 72% compared to control. Adding of curcumin to the cardiomyocyte cell culture contributed to increasing of the Mn-SOD activity by 14%, catalase--by 23%. The level of TBARS increased by 1,4 times compared with the control, and the level of H2O2 increased by 20%. The joint use of doxorubicin and curcumin resulted in a significant reduction of free radical oxidation unlike effect of doxorubicin per se. Specifically, there was lessening of TBARS and H2O2 (at 56.7 and 18.4% respectively), while decreasing of the catalase hyperactivation (19%) and rising of the Mn-SOD activity (35%). PMID- 26845850 TI - [FEATURES OF ADAPTIVE REACTIONS IN HUMANS UNDER POWER FITNESS]. AB - We studied the features of adaptive reactions of human body under conditions of power loads of different volume and intensity. It was found that an increase in the testosteron concentration in blood plasma of untrained young men to 23.2% (P < 0.05) after exercise, compared with the state of rest takes place in response to the high power loads intensity. At the same time, medium intensity work with large amount of workload reduced the concentration of these hormones by 14.3% (P < 0.05). During long-time training an increase in maximum parameters of muscle force (by 32.5% in control and 53.1% in test group) was observed. Thus, adaptive changes in the process of sustained power fitness are characterized by a slowdown of muscle strength and body size in both groups compared with baseline values, which were established after the first month of training. At the same time it was found that the hormonal response to acute power load becomes more pronounced with each subsequent month of classes in fitness force only under the conditions of use during the training sessions of high-intensity physical exercise for a small amount of work. PMID- 26845851 TI - [GLYCINE RECEPTOR: MOLECULAR ORGANIZATION AND PATHOLOGY]. AB - Glycine receptor is the anion-selective channel, providing fast synaptic transmission in the central nervous system of vertebrates. Together with the nicotinic acetylcholine, GABA and serotonin (5-HT3R) receptors, it belongs to the superfamily of pentameric cys-loop receptors. In this review we briefly describe main functions of these transmembrane proteins, their distribution and molecular architecture. Special attention is paid to recent studies on the molecular physiology of these receptors, as well as on presenting of molecular domains responsible for their dysfunction. PMID- 26845853 TI - [The Role of Su(Hw) Protein in Transcription Regulation in Drosophila melanogaster]. AB - Insulators are regulatory DNA elements that modulate the effect of enhancers and silencers on gene transcription. However, the role of the insulator complex proteins in the expression of specific genes remains scarcely studied. In the present study, we examined the role of the Su(Hw)-dependent insulator complex in transcription of the rap, CG32810, and RpS15Aa genes. It was demonstrated that the interaction of Su(Hw) and Mod(mdg4)-67.2 insulator proteins with the terminator regions of the selected genes was dependent on the Su(Hw) factor. At the same time, the CP190 protein also interacts with the promoter and terminator regions in the absence of Su(Hw). In addition, the Su(Hw) protein does not affect the level of transcription and silencing efficiency of the gene models. A possible explanation for these results is the existence of another transcription factor, a protein that is able to recruit CP190 and functionally compensate for the lack of the Su(Hw) protein. PMID- 26845852 TI - [Master Transcription Regulators Specifying Cell-Lineage Fates in Development As Possible Therapeutic Targets in Oncology]. AB - The transformation of normal precursors into cancer cells is an intricately regulated, multistep process. The master regulatory genes that play a crucial role in the process of organism development may also play a key role in carcinogenesis. From such a point of view, cancer is not simply a genetic disease that is due to a progressive accumulation of mutation--it is also a disorder of the developmental system of the tissue in which cancer emerges. Master regulators and their genes disturb stem cell differentiation upon mutation and thus may serve as targets for cancer therapy, in addition to the classic oncogenes and suppressors of tumor formation. This review is an attempt to give a modern concept of master genes and their functions in adult stem cells of the organism and in carcinogenesis, with pancreatic cancer as an example. PMID- 26845854 TI - [Sorbitol-6-Phosphate Dehydrogenase Gene Polymorhism in Malus Mill. (Rosaceae)]. AB - The sorbitol-6-phosphate dehydrogenase gene (S6PDH) sequences of six representatives of the genus Malus, which belong to five different taxonomic sections, were examined for the first time. The exon-intron structure and polymorphism of the nucleotide and amino acid sequences of these genes was characterized. The intraspecific polymorphism of the S6PDH gene was assessed for the first time in 40 Russian and foreign apple (Malus domestica) cultivars. It was demonstrated that the interspecific polymorphism level of the S6PDH coding sequences in the studied. representatives of the genus Malus was 4%, and the intraspecific polymorphism level of M. domestica cultivars was very low, constituting 0.96%. PMID- 26845855 TI - [Analysis of mtDNA and Nuclear Markers Points to Homoploid Hybrid Origin of the New Species of Far Eastern Redfins of the Genus Tribolodon (Pisces, Cyprinidae)]. AB - The nucleotide sequences of two mitochondrial genes (cytochrome c oxidase subunit I, COI, and cytochrome b, cyt b) and four nuclear genes (growth hormone gene GH1, ribosomal protein S7 gene RP1, recombination activating gene RAG1, and rhodopsin gene RH) from the Far Eastern redfins of the genus Tribolodon were examined to clarify the status of the southern form of T. hakonensis. Nucleotide sequence analysis of the mitochondrial genes showed differences of 2.6% between individuals of T. hakonensis inhabiting the north and south of the range. Analysis of the nuclear genes showed that Tribolodon sp. (southern form of T. hakonensis) has a mosaic of nuclear genes received from the Pacific redfin T. brandtii and big-scaled redfin T. hakonensis. It is suggested that the new species could have formed as a result of homoploid hybridization between the true T. hakonensis (by original description) and T. brandtii, which probably made it possible for this species to occupy a new ecological niche. PMID- 26845856 TI - INVESTIGATION OF STAT5A, FSHR AND LHR GENE POLYMORPHISMS IN TURKISH INDIGENOUS CATTLE BREEDS (EAST ANATOLLAN RED, SOUTH ANATOLIAN RED, TURKISH GREY, ANATOLIAN BLACK AND ZAVOT). AB - The objective of this study was to examine the allelic and genotypic profiles of the Signal Transducer and Activator of Transcription 5A (STAT5A), Follicle Stimulating Hormone Receptors (FSHR), and Luteinizing Hormone Receptor (LHR) genes in five indigenous cattle breeds in Turkey. For this purpose, a total of 329 cattle from East Anatolian Red (EAR), South Anatolian Red (SAR), Turkish Grey (TG), Anatolian Black (AB), and Zavot were genotyped using by PCR-RFLP method. A215 bp fragment of STAT5A, a 306bp fragment of FSHR, and a 303 bp fragment of LHR were amplified and digested with AvaI, AluI, and HhaI restriction enzymes, respectively. In this study two types of alleles C and Tfor STAT5A, C and G for FSHR and C and T for LHR were observed. The highest frequencies for STAT5A-C and STAT5A-T alleles were estimated for the Zavot and TG breeds (0.86) and the EAR breed (0.29), respectively. The highest frequency for FSHR-C and FSHR-G alleles was estimated for the Zavot breed (0.72) and the AB and SARbreeds (0.35), respectively. The highest frequency for LHR-C and LHR-T alleles was estimated for the EAR breed (0.75) and the AB breed (0.39), respectively. According to FT values, a small level of genetic diversity was found among five cattle breeds. The F(ST) value was calculated 0.019 between AB and Zavot. And, the value was significant (p < 0.001), while the other F(ST) values were not significant. According to the genetic distance values (Nei), the highest genetic distance was found between AB and TG while the smallest genetic distance was found between Zavot and TG. The chi-square test showed that the TG and Zavot breeds were in Hardy-Weinberg equilibrium (HWE) for STAT5A gene; the EAR, SAR, TG, and Zavot breeds were in HWE for FSHR gene and the EAR, SAR, and TG breeds were in HWE for LHR gene. In conclusion, further investigation is required to determine the correlation of the FSHR and LHR genes with early puberty for the improvement of sexual precocity, and it is considered that the STAT5A gene may be used to improve the milk yield and milk yield traits of local cattle breeds, including those indigenous to Turkey. PMID- 26845857 TI - [The System of the Suborder Zoarcoidei (Pisces, Perciformes) as Inferred from Molecular Genetic Data]. AB - Based on an analysis of sequence variation in mitochondrial and nuclear markers, the levels of divergence, relationships, and system of the suborder Zoarcoidei was defined. It was demonstrated that DNA lineages of the families Bathymasteridae and Cebidichthyidae were positioned at the bottom ofthe suborder phylogenetic tree. The family Zoarcidae is a monophyletic group, the youngest in the evolutionary terms. Zoarcidae, Anarhichadidae, Neozorcidae, and Eulophiidae form a group of related families. The family Stichaeidae is heterogeneous and has a polyphyletic origin; within this family, the subfamilies Chirolophinae, Alectgiinae, Xiphisterinae, and Stichaeinae are sister taxa. The subfamilies Opisthocentrinae and Lumpeninae are isolated from Stichaedae; Opisthocentrinae is closely associated with the families Pholidae and Ptilichthyidae, and Lumpeninae is closely associated with Zaproridae and Cryptacanthodidae. It is suggested that the rank of subfamilies Opisthocentrinae and Lumpeninae should be raised. PMID- 26845858 TI - [Mitochondrial Genome Variability in the Wolverine (Gulo gulo)]. AB - The nucleotide sequence of an extended mitochondrial genome segment (11473 base pairs in size) was determined in the wolverine (Gulo gulo) from Magadan oblast. Phylogenetic and statistical analyses of mitochondrial DNA (mtDNA) sequences of mustelids showed that the separation of the Gulo phylogenetic branch occurred at the Miocene--early Pliocene (about 5.6 million years ago (MYA)), while the formation of the species G. gulo took place in the Middle Pleistocene (181 and 234 thousand years ago (KYA), according to the results of molecular dating based on the variability of the extended mtDNA segment and the mitochondrial cytochrome b gene, respectively). The molecular data were in agreement with the fossil records for wolverines. PMID- 26845859 TI - POLYMORPHISM IN THE CODING REGION SEQUENCE OF GDF8 GENE IN INDIAN SHEEP. AB - The present study was undertaken to identify polymorphism in the coding sequence of GDF8gene across indigenous meat type sheep breeds. A 1647 bp sequence was generated, encompassing 208 bp of the 5'UTR, 1128 bp of coding region (exon1, 2 and 3) as well as 311 bp of 3'UTR. The sheep and goat GDF8 gene sequences were observed to be highly conserved as compared to cattle, buffalo, horse and pig. Several nucleotide variations were observed across coding sequence of GDF8 gene in Indian sheep. Three polymorphic sites were identified in the 5'UTR, one in exon 1 and one in the exon 2 regions. Both SNPs in the exonic region were found to be non-synonymous. The mutations c.539T > G and c.821T > A discovered in this study in the exon 1 and exon 2, respectively, have not been previously reported. The information generated provides preliminary indication of the functional diversity present in Indian sheep at the coding region of GDF8gene. The novel as well as the previously reported SNPs discovered in the Indian sheep warrant further analysis to see whether they affect the phenotype. Future studies will need to establish the affect of reported SNPs in the expression of the GDF8 gene in Indian sheep population. PMID- 26845860 TI - [Molecular Karyotyping of Cell-Free DNA from Blastocoele Fluid as a Basis for Noninvasive Preimplantation Genetic Screening of Aneuploidy]. AB - The discovery of DNA fragments in the blastocoele fluid is promising for the development of new noninvasive methods for the preimplantation genetic diagnosis of chromosomal diseases. However, to date there are no data confirming the concordance between the molecular karyotype of cell-free DNA from blastocoele fluid and the blastocyst cells per se. This paper reports on this concordance according to the results of molecular-cytogenetic analysis of the chromosomal set with the use of comparative genomic hybridization. PMID- 26845861 TI - [Comparative Analysis of Polymorphisms of the Serotonin Receptor Genes HTR1A, HTR2A, and HTR1B in Hadza and Datoga Males]. AB - The distribution of the allele and genotype frequencies of polymorphic loci of serotonin receptor genes (HTR1A, rs6295; HTR2A, rs6311; HTR1B, rs6296) in Hadza (n = 197) and Datoga males (n = 230) living in Tanzania was determined. It was shown that the populations significantly differ by the frequencies of alleles and genotypes of the rs6295 locus of the HTR1A gene. The G-allele (0.779) and the genotype G/G (0.590), which are markers of increased risk of suicidal and impulsive behavior, respectively, are revealed in Hadza with high frequency. It was found that the frequency of homozygous G/G of the rs6296 locus of the HTR1B gene, which is a marker of increased risk of outward directed aggression, is higher in Datoga (0.563) than in Hadza (0.457). The allele and genotype frequencies of the rs6311 locus of the HTR2A gene do not differ among the Hadza and Datoga males. The data on the distribution of allele and genotype frequencies of the HTR1A, HTR2A, and HTR1B genes can be used to determine the associations of the identified markers with various forms of human aggressive behavior. PMID- 26845863 TI - [A Simple and Efficient Method of Inducing Targeted Deletions in the Drosophila Genome]. AB - Deletion mutagenesis is one of the most efficient approaches to studying gene function. However, conventional methods of inducing targeted mutations in the drosophila genome are time- and labor-consuming. This work proposes a new, simple, and effective method of producing drosophila mutants with gene deletions. The method involves the insertion of I-Scel and I-CreI recognition sites and a fragment homologous to the target sequence into the chromosome region of interest by means of an attB-containing construct, the induction of double-strand DNA breaks by the appropriate meganuclease, and their repair by homologous recombination. The procedure results in a deletion extending from the attP-site to the target locus. A cassette was designed to enable single-step construct production for the deletion of any given genomic region. A set of markers facilitates the selection of recombination events. The efficacy of the proposed technique was confirmed by the induction of a 47-kb deletion containing the qtc gene. PMID- 26845862 TI - [Association of Polymorphic Variants of Gene MUC19 with Asthma in Russians According to the Results of a Genome-Wide Study]. AB - Asthma is a heterogeneous multifactorial disease that is characterized in most cases by chronic respiratory tract inflammation. We carried out a GWAS in order to identify susceptibility genes for asthma in individuals of different ethnic backgrounds. The study sample consisted of 358 unrelated patients with asthma (160 Russians, 125 Tatars, and 73 Bashkirs) and 369 individuals of a control group (152 Russians, 117 Tatars, and 100 Bashkirs). DNA samples were genotyped with an Illumina human610 quad array (Illumina) as part of the project GABRIEL. Replication of the results of genome-wide analysis was carried out on an additional independent sample of 310 asthma patients (132 Russians, 105 Tatars, and 73 Bashkirs) and 310 individuals in a control group (131 Russians, 106 Tatars, and Bashkirs 77). Genome-wide analysis showed an association of asthma in Russians with the polymorphic loci of gene MUC19 (12q12) encoding gel-forming mucin 19. The highest level of association with asthma was found in rs2933346, which is located in intron 52 of this gene (p = 2.59 x 10(-6)). Seven polymorphic loci of gene MUC19 (rs1492313, rs2588401, rs2588402, rs2638863, rs2638864, rs1352940, and rs2933373), which are in close linkage disequilibrium among themselves and rs2933346, are associated with asthma with the same p-value (p = 4.96 x 10(-6)). The replicative study of rs1492313 in the independent sample of individuals confirmed the presence of the association of the polymorphic loci of this gene with the development of asthma in Russians. According to our data, the association of polymorphic variants of gene MUC19 with asthma has not been previously identified in any study. Our results indicate the important role of polymorphic variants of gene MUC19 in the formation of a predisposition to the development of asthma in individuals of Russian ethnicity. PMID- 26845864 TI - [Intraspecific Variability of ITS Sequences in the Parasitic Plant Monotropa hypopitys L. from the European Russian Populations]. AB - Intraspecific sequence polymorphism in the ITS region of the nuclear ribosomal operon was examined in ten populations of the parasitic plant Monotropa hypopitys from Belgorod oblast, Vologda oblast, and Kaluga oblast of Russia. Based on an analysis of the identified nucleotide substitutions and indels in the ITS regions, the M. hypopitys populations were divided into two groups (A and B). Four new ITS haplotypes of M. hypopitys were identified. PMID- 26845865 TI - [Bleaching of Baikalian Sponge Affects The Taxonomic Composition of Symbiotic Microorganisms]. AB - The diversity of 16S rRNA genes in the microbial community of endemic sponge Lubomirskia baicalensis with bleached patches of tissue was studied. Eight bacterial phyla were identified in the sponge microbiome: Cyanobacteria (27.3%; n = 36; 2 OTU, operational taxonomic unit), Proteobacteria (22.7%; n = 30; 5 OTU), Actinobacteria (16.7%; n = 22; 7 OTU, operation taxonomic unit), Verrucomicrobia (15.2%; n = 20; 4 OTU), Plactomycetes (9%; n = 12; 3 OTU), Bacteroidetes (4.5%; n = 6; 3 OTU), WS5 (3%; n = 4; 1 OTU), and TM7 (1.5%; n = 2; 1 OTU). The basic phyla typical of freshwater sponge microbiomes are present in the community. However, in contrast to previously studied L. baicalensis bacterial associations, a dominance of Cyanobacteria and a low number of representatives of the Bacteroidetes and Betaproteobacteria were observed in the bleached sponge community. Phylotypes exhibiting a high percentage of similarity with the microorganisms inhabiting substrates rich in organic matter were also found. Clearly, the bleaching processes of Baikal sponges affect the composition and the ratio of the major taxonomic groups of sponge-associated bacteria. PMID- 26845866 TI - [Optical coherence tomography angiography in the diagnosis of neovascular age related macular degeneration]. AB - AIM: to determine optical coherence tomography (OCT) angiography signs of classic and occult choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) and evaluate their information value in monitoring the effect of anti-VEGF therapy. MATERIAL AND METHODS: The study enrolled 76 patients (87 eyes), including 68 patients (72 eyes) with wet AMD and 8 patients (15 eyes) with no signs of neovascularization. All patients underwent spectral-domain OCT, OCT angiography, and fluorescein angiography (FA). OCT angiography was used to evaluate neovascular networks in terms of their location, shape, size, and extent of visualization. Sensitivity and specificity of the method were assessed separately in a group of 37 CNV eyes and 15 unsuspicious eyes, specific findings at FA being the main diagnostic criteria. To determine the information value of OCT angiography in monitoring the effect of intravitreal ranibizumab therapy, 9 patients (9 eyes) were selected, in whom the exam was performed the day before the injection and then at days 3, 10, 17, 24, and 31. RESULTS: The patients were divided into two groups. Group 1 consisted of 43 eyes with occult CNV, group 2- of 29 eyes with classic CNV. Neovascular loops underneath the retinal pigment epithelium were found in 76.74% of occult CNV cases. In patients with classic CNV, the neovasculature was clearly visible in 82.76% of eyes, loop-like and tree like networks occurring with similar frequency (51.72% and 42.28% respectively). OCT angiography results obtained prior to and following ranibizumab injection revealed a change in not only the size of neovascularization, but also the density, thickness, and branching pattern of newly formed blood vessels. Sensitivity and specificity of OCT angiography has been shown to be 89.2% and 93.3% respectively. CONCLUSION: OCT angiography enables diagnosis of both classic and occult choroidal neovascularization in patients with AMD as well as dynamic assessment of the size of the neovascular complex during anti-VEGF treatment. The method has high sensitivity and specificity. PMID- 26845867 TI - [Ocular blood flow and retinal electrogenesis in retinitis pigmentosa]. AB - AIM: to investigate correlations between changes in ocular hemodynamics revealed by color Doppler flow mapping (CDFM) and pulsed-wave (PW) Doppler imaging, one the one hand, and electrical activity of the retina, on the other, in patients with early, moderate, and severe retinitis pigmentosa (RP). MATERIAL AND METHODS: A total of 20 patients (40 eyes) aged from 16 to 40 years (28.4 +/- 8.2 years on average) with retinitis pigmentosa were enrolled. The control group consisted of 20 healthy volunteers of the same age range. All participants underwent full field electroretinography (ERG), flicker ERG, and macular ERG as well as blood flow assessment in the ophthalmic artery (OA), central retinal artery (CRA), and short posterior ciliary arteries (SPCA) by means of CDFM and PW-Doppler. RESULTS: Ocular blood flow in CRA and SPCA appeared disturbed in patients with early RP. In cases of moderate and severe RP, the peak systolic velocity of CRA and SPCA blood flow was significantly decreased. Systolic and end diastolic blood flow velocities in CRA and SPCA has been shown to be directly related to full-field ERG a-wave and b-wave amplitudes, correspondingly, but negatively correlated with their implicit times. CONCLUSION: The revealed decrease in CRA and SPCA blood flow indices proves retinal and choroidal circulation deficit in patients with advanced RP. As shown, moderate blood flow changes are already present in early RP and progress as retinal photoreceptors and bipolar cells become suppressed, which may be useful for RP diagnosis and monitoring. PMID- 26845868 TI - [Variability in biomechanical properties of the fibrous tunic of the eye in a healthy population]. AB - Studying biomechanical properties of the fibrous tunic of the eye meets current clinical demands. Previous studies have proved bidirectional corneal applanation suitable for this purpose. The so called corneal elasticity coefficient is more informative in terms of corneal elastance than the two other parameters measured during bidirectional corneal applanation, namely, corneal resistance factor and corneal hysteresis. All three are known to have wide normal ranges. The aim of the present study was to determine the range of corneal resistance factor, corneal hysteresis, and corneal elasticity coefficient in a normal population. MATERIAL AND METHODS: This work summarizes data from 2205 patients (4410 eyes) with no ophthalmic pathology who got their ocular biomechanics examined with an Ocular Response Analyzer. RESULTS: Normal ranges of biomechanical parameters of the fibrous tunic have been determined. Considerable variation has been demonstrated in central corneal thickness (from 448 to 685 um, with the mean of 563 +/- 37 um). Moreover, the corneal resistance factor, corneal hysteresis, and corneal elasticity coefficient have been shown to have almost equal means and to decrease with age. PMID- 26845869 TI - [Intraocular lens power calculation in silicone-filled eyes]. AB - AIM: to evaluate the accuracy of different modified methods for axial length (AL) measurement in silicone-filled eyes. MATERIAL AND METHODS: The study was conducted in a group of 60 patients (60 eyes) with silicone oil tamponade (Oxane 1300 cst). Axial length measurements were taken using IOL Master optical coherence biometry ('silicone-filled eye' mode) and modified A-scan ultrasound biometry (velocity of ultrasound passing through the vitreous body set at 980 m/s and 1000 m/s). After phacoemulsification and silicone oil removal, AL measurements were repeated on same devices switched to standard pseudophakia modes. The results were then compared to those obtained in modified modes before the surgery. RESULTS: Preoperative axial lengths measured by A-scan at 980 m/s tended to be 0-1.5 mm (the median of 0.52 mm) shorter than those obtained after silicone oil removal. With 1000 m/s ultrasound velocity the error was much less- from 0 to 0.5 mm (the median of 0.15 mm). As for preoperative ALs by IOL Master in the 'silicone-filled eye' mode, they were 0-1.2 mm (the median of 0.3 mm) longer than postoperative ones. CONCLUSIONS: In cases of impossibility or inaccessibility of optical biometry, measurements taken with an A-scan device set at 1000 m/s are sufficient. The true AL of an eye with silicone oil tamponade falls somewhere between the values obtained with 1000 m/s ultrasound and IOL Master in the 'silicone-filled eye' mode. PMID- 26845870 TI - [Anatomical parameters of emmetropic and varyingly myopic eyes]. AB - This article summarizes the results of a study on ocular anatomy in emmetropia and different degrees of myopia conducted in the Smolensk State Medical Academy. Data of 233 patients (408 eyes) is presented. Five size parameters were measured in all cases. A mathematical model of an emmetropic eye has been developed. The results obtained allow to judge the dimensions of a normal eyeball and their changes in case of myopia progression. PMID- 26845871 TI - [Long-term efficacy of corneal collagen cross-linking in patients with progressive keratoconus]. AB - AIM: to study the efficacy of corneal collagen cross-linking in patients with progressive keratoconus over longer (up to 2 years) follow-up periods. MATERIAL AND METHODS: A total of 52 patients (104 eyes) aged 23-34 years with stage I-III progressive keratoconus were enrolled. Besides routine examinations (automatic refractometry, uncorrected and best corrected visual acuity (UCVA and BCVA) evaluation, pneumatic tonometry), Pentacam keratotopography and pachymetry ("Oculus", Germany) were performed in all cases. Corneal biomechanical properties were assessed with an Ocular Response Analyzer ("Reichert", USA). In all patients cross-linking procedure was carried out in the eye with more advanced keratoconus, the fellow eye being used as the control. RESULTS: Judging from the results of UCVA and BCVA evaluation, keratotopography, and pachymetry obtained 2 years after the standard corneal cross-linking procedure, stabilization has been achieved in 97% of cases. In the remaining 3% of eyes corresponding parameters declined, although to a lesser extent than in the controls. Indices describing biomechanical properties of the cornea, such as corneal hysteresis, corneal resistance factor, as well as elastonometry results did not differ significantly throughout the whole observation period, which agrees with literature data. CONCLUSION: Corneal collagen cross-linking has been proved capable of stopping keratoconus progression in most of the patients (97%). Further studies with even longer follow-up periods are needed. PMID- 26845872 TI - [Study of common cytotoxicity of aminoglycoside and fluoroquinolone antibiotics in cell cultures]. AB - The aim of the study was to identify the overall cytotoxicity of aminoglycosides netilmicin and tobramycin, and fluoroquinolone ciprofloxacin. MATERIAL AND METHODS: We used three types of the cells: constantly transformed cell line CHO K1, normal human skin fibroblasts and cells of normal human conjunctiva Clone 1 5C-4. Antibiotics activity was detected by their influence on cell viability. Quantitative and qualitative methods of evaluation have used to determine viability of the cells (quantitative assessment: a method of cloning cells and colorimetric method for assessing cell proliferation; qualitative assessment: lifetime visual observation under an inverted microscope for morphological status of cells in culture with photofixing). RESULTS: The most toxic effect for all types of the cells was shown in tobramycin. The least degree of toxicity for all types of the cells was determined in netilmicin. CONCLUSION: Studied antibiotics exert a cytotoxic effect in vitro and differ in their cytotoxic potential. PMID- 26845873 TI - [Epidemiology of traumatic eye injuries among the population of Azerbaijan Republic]. AB - The aim of the present study was to examine the main trends in traumatic injuries of the eye and eye socket among the population of Azerbaijan Republic. Absolute and intensive (per 100,000 population) indices, gender and age-related differences over the period of 2006-2011 have been studied. As shown, the occurrence of traumatic injuries of the eye and eye socket per 100,000 population has been increasing over the said time frame being generally higher in big cities. Injuries of this kind are characterized by age- and gender-related differences. Household injury accounts for the most of them. PMID- 26845874 TI - [Influence of antihypertensive therapy on morphofunctional and biomechanical parameters of eyes]. AB - SHORTHEADER: biomechanical parameters of the eye on antihypertensive therapy. PURPOSE: to establish correlation of main biomechanical parameters of cornea depends on conducted antihyperthensive therapy and morphofunctional condition of cornea. MATERIAL AND METHODS: 58 patients (62 eyes) with POAG were included in the dynamic study in the period from 36 to 42 months. Patients were divided into two groups depending on the values of corneal hysteresis (CH) in the first part of the study. The value of CH in the first group (37 eyes) was in normal ranges 8,3-12,4 mm of mercury, in the second group (25 eyes) CH value has been reduced to 5.6-8.2 mm of mercury. In the second part of the study brimonidine/ timolol fixed combination (Combigan, Allergan) was prescribed as adjunctive therapy for the patients from the group 2 with low CH level. The following scheme of instillations was recommended--1 drop 2 times a day with interval of 12 hours. We evaluated the subjective and objective measures of structural and functional condition of the eye after 1, 3, 6, 12 and 18 months. RESULTS: In the first part of the study of the dynamics of morphological and functional parameters of the optic nerve at different values of the CH, it was found that if CH < 8.2 mm of mercury structural and functional changes of optic nerve are more pronounced and significantly increases the risk of progression of glaucomatous process that requires correction of antihypertensive treatment. In the second part of the study in a group of dynamic observation with low CH level considering the negative structural and functional dynamics of antihypertensive therapy was corrected by Combigan(r) administration. Add-on therapy (Combigan) had a statistically significant effect on IOP, lowering it at average on 4.6 mm of mercury, and on the CH level, increasing it at average on 2.3 mm of mercury. Analysis of changes in perimeter sLV index showed a reduction of numbers of relative defects of various depths (from 8.9 dB to 6.9 dB). Analysis of optical coherent retinotomography data with brimonidine/timolol instillation on the background showed a tendency to increase the average thickness of retinal nerve fibers (from 0.11 to 0.18 mm). Dynamic observation for 18 months showed the stability of structural and functional parameters of the optic nerve disc, i.e. the target pressure for these patients has been achieved. CONCLUSION: Administration of fixed combination brimonidine/timolol (Combigan) in combined therapy for the patients with POAG and low level of CH leads to normalization of biomechanical parameters of the eye and stabilization of glaucomatous process. PMID- 26845875 TI - [Therapeutic methods of scar prevention at the site of endonasal dacryocystorhinostomy]. AB - Success rate of endonasal dacryocystorhinostomy (DCR) varies from 82% to 91%. The bulk of unsatisfactory results is due to excessive scarring at the site of the created opening (dacryostoma, DS). Mitomycin C is the most extensively studied drug of those affecting regeneration processes, however, the data on its efficacy at DS site is contradictory. Despite ongoing search for new agents able to interfere in the physiological process of scarring, the number of relevant studies is yet insufficient. Thus, development of methods of scarring prevention after endonasal DCR takes the highest priority in dacryology. PMID- 26845876 TI - [Review of approaches to cell therapy in ophthalmology]. AB - The review covers global trends in cell therapy research and clinical trials aimed at the treatment of ophthalmic diseases. Some definitions are provided and mechanisms of action of cell products studied to date are listed. PMID- 26845877 TI - [Ophthalmic manifestations of Huntington's disease]. AB - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutation in the huntingtin gene. The whole nervous system, including visual analyzer, is involved in the pathogenesis of the disease. Various ocular sings can be found in both preclinical and clinical stages of HD. Specific retinal damage, namely, abnormal proteins formation, photoreceptor degeneration and retinal remodeling, has been studied in animal models. Functional changes in occipital lobe activity and its atrophy as well as degeneration of visual pathways can already be present in the early stages of the disease. Oculomotor symptoms of HD include disturbed visual fixation, slower tracking eye movements and saccades, and suppressed vestibulo-ocular reflex. Visual perceptual disorders, such as visuospatial difficulties, problems of stimulus identification and motion perception, along with decreased contrast sensitivity, have also been described. The possibility of using certain ophthalmic parameters as biomarkers of HD is being discussed. PMID- 26845878 TI - [Purulent corneal ulcers: etiology, pathogenesis, classification]. AB - Advanced purulent corneal ulcer, as well as abscess, is a serious vision threatening condition notable for its fulminant course and possible loss of the eye due to endophthalmitis. Its leading causes, pathogenesis, and classifications are described and analyzed in this paper. PMID- 26845879 TI - [Corneal damage in patients with thyroid eye disease]. AB - This is a review of literature on etiology, pathogenesis, risk factors, and treatment of thyroid-associated keratopathy. Both Russian and foreign sources have been thoroughly examined. PMID- 26845880 TI - [Current data on the role of anthocyanosides and flavonoids in the treatment of eye diseases]. AB - Anthocyanins are known to have antioxidant, anti-inflammatory, neuroprotective, and anticarcinogenic activity as well as positive effect on the cardiovascular system. Because of bilberry anthocyanosides (Vaccinium myrtillus L.), Mirtilene forte promotes rhodopsin synthesis and regeneration, increases retinal sensitivity to changes in light intensity, improves visual acuity and dark adaptation as well as blood supply of the retina. Studies conducted in Russia are aimed at evaluating the use of Mirtilene forte in age-related macular degeneration, diabetic retinopathy, primary open-angle glaucoma, and other diseases. This article provides an analysis of foreign and Russian publications on the effects of anthocyanins and flavonoids in different diseases. PMID- 26845881 TI - [Electrophysiological evaluation of retinal function after systemic and superselective intra-arterial chemotherapy for retinoblastoma]. AB - Since the prognosis for visual acuity after polychemotherapy or superselective intra-arterial chemotherapy (SIACT) is doubtful, studying retinal function in children with retinoblastoma by means of clinical electroretinography (ERG) is a relevant issue. The latter enables objective post-treatment assessment of retinal function and evaluation of possible infusion-related retinal toxicity. This review analyzes ERG findings in children with retinoblastoma treated with chemotherapy, including SIACT. PMID- 26845882 TI - [New data on the contribution of F. Hiltebrandt to the establishment and development of ophthalmology at the Imperial Moscow University]. AB - The article provides F. Hiltebrandt's biography and analyzes his contribution to the establishment of ophthalmology service at the Imperial Moscow University and its further development. PMID- 26845883 TI - [ROLE OF FRAILTY ASSESSMENT IN PATIENTS UNDERGOING SURGERY]. PMID- 26845884 TI - [HISTORY OF JOURNAL OF JAPAN SURGICAL SOCIETY]. PMID- 26845885 TI - [NONCODING RNA: SIGNIFICANCE IN SURGICAL ONCOLOGY]. PMID- 26845886 TI - [CANCER REPROGRAMMING AND ITS CLINICAL APPLICABILITY]. AB - Although cancer is a genetic disease, epigenetic alterations are involved in its initiation and progression. Previous studies showed that the introduction of endogenous small-sized, noncoding ribonucleotides including microRNA200c, -302s, and -369 resulted in the induction of cellular reprogramming. MicroRNA200c inhibits the epithelial-mesenchymal transition. MicroRNA302s induces the demethylation of the tumor suppressor gene promoter region, while microRNA369 changes cancer cell metabolism. These three types of microRNA induce cancer cellular reprogramming and modulate malignant phenotypes of human cancer cells. These results suggest that the appropriate delivery of functional small-sized ribonucleotides may be a novel approach to the treatment of human cancer. PMID- 26845887 TI - [SIGNIFICANCE OF NONCODING RNAS IN COLORECTAL CANCER: REVIEW]. AB - Recent advances in the field of RNA research have shown that microRNAs (MiRNAs) are among noncoding RNAs that function in posttranscriptional regulation of target gene expression via base-pairing with complementary sequences in mRNAs to induce mRNA degradation and translational inhibition. Together with several causes of colorectal cancer (CRC) initiation and progression which are regulated by both genetic and epigenetic modifications, aberrant expression of oncogenic and tumor suppressor MiRNAs in cancer cells was found to be up- or downregulated by targeted mRNAs specific to tumor promoter or inhibitor genes. In particular, the study of MiRNAs as CRC biomarkers utilizes expression profiling methods from tissue samples along with newly introduced noninvasive samples of feces and body fluids, since MiRNAs are known to be extremely stable under several conditions. Additionally, MiRNAs could be employed to predict chemo- and radiotherapy responses and be manipulated in order to alleviate CRC characteristics. This article introduces progress in the utilization of MiRNAs as noninvasive biomarkers for cancer detection, estimation of recurrence and prognosis, and prediction of chemotherapeutic agent response in CRC. It also discusses the obstacles that have limited the routine use of MiRNA biomarkers in the clinical setting. PMID- 26845888 TI - [CLINICAL SIGNIFICANCE OF NONCODING RNA IN HEPATOCELLULAR CARCINOMA]. AB - RNAs lacking protein-coding ability are called "noncoding RNAs" (ncRNAs). ncRNAs include microRNA (19-24 nucleotides in length) and long ncRNA (lncRNA). MicroRNA binds to the 3'-untranslated regions of target mRNAs and regulates target genes at a posttranscriptional level. In hepatocellular carcinoma (HCC), the roles of microRNAs in hepatocarcinogenesis and microRNAs that can determine the nature of HCC have been reported. Because microRNA is stable in the bloodstream or formalin fixed specimens, it can be used as a tumor marker. MicroRNAs as therapeutic targets for HCC are being intensively investigated. A phase I clinical study using miR-34 is currently in progress. On the other hand, the investigation of lncRNAs has only recently begun. Because lncRNAs are also involved in hepatocarcinogenesis and can determine the nature of cancers, many researchers are now working on these RNAs. PMID- 26845889 TI - [SIGNIFICANCE OF NONCODING RNA IN BREAST CANCER]. AB - Noncoding RNA (ncRNA) has a crucial role in the molecular mechanisms of malignant features of breast cancer. This review outlines the biological and clinical significance of well-investigated microRNAs including let-7, miR-21, miR-200, miR 15/16, miR-155, and miR-221/222, and long ncRNAs such as H19, LSINCT5, HOTAIR, and GAS5. The biological roles of microRNAs secreted in the exosome are also described. Combined analysis of mRNA and ncRNA will help to develop the field of genetic diagnosis of breast cancer. PMID- 26845890 TI - [SIGNIFICANCE OF NONCODING RNA IN SURGERY: NONCODING RNA IN LUNG CANCER]. AB - Recent advances in cancer research have revealed that noncoding RNAs such as microRNAs and long noncoding (lnc) RNAs play important roles in various cancers including lung cancer. Noncoding RNAs have the potential to become new biomarkers of cancer in the clinical setting, that is, they may be useful for the early detection, prognostic prediction, and prediction of sensitivity to chemotherapy and radiotherapy. It is also expected that noncoding RNAs can become new therapeutic targets. Aberrant expression of several microRNAs and lncRNAs has been reported in lung cancer, and there is a possibility of the identification of new therapeutic targets in the near future. To contribute to improved outcomes of lung cancer treatment, it is necessary to detect patients who are candidates for surgery in an earlier stage to increase the number undergoing radical surgery and to select those who are at high risk of recurrence postoperatively to increase opportunities for treatment to prevent it. Thus, it is important to discover new biomarkers for lung cancer. Surgeons can take the initiative in research, as they have easy access to specimens from lung cancer patients. PMID- 26845891 TI - [THERAPEUTIC POTENTIAL OF MICRORNA IN THE FIELD OF CARDIOVASCULAR SURGERY]. AB - Because the number of heart failure patients increases every year, improved prevention and treatment for damaged hearts are needed. Many investigators have explored new approaches to improve cardiac function, including cell transplantation and gene therapy. MicroRNAs comprise a novel class of endogenous, small, noncoding RNAs that negatively regulate gene expression via degradation or translational inhibition of their target mRNAs. Recent studies have described microRNAs as fine-tuners of gene expression. New therapeutic strategies for heart failure using microRNAs such as cardiac reprogramming therapy by overexpression of microRNAs in murine infarcted hearts and prevention of cardiac remodeling using antagomirs in hypertensive rat models are promising technologies for future clinical application. Moreover, microRNAs could possibly function as biomarkers of heart failure. MicroRNA-145 is a specific mediator of the regulation of the vascular smooth muscle cell phenotype. We reported that transduction of microRNA 145 into vein grafts may be a novel option for preventing vein graft disease after surgical revascularization, since its transduction reduced neointimal thickness in the rabbit model of vein graft disease. Although several issues regarding microRNAs need to be overcome, their therapeutic potential holds considerable promise, and they will hopefully be combined with surgical strategies in the near future. PMID- 26845892 TI - [STRATEGY FOR THE TREATMENT OF UNRESECTABLE LUNG CANCER]. PMID- 26845893 TI - [WHAT WE CAN LEARN FROM A CASE OF MEDICAL MALPRACTICE--MEDICAL INSTITUTION IS HELD LIABLE FOR NEGLIGENCE INVOLVING A PHLEBOTOMY ACCIDENT]. PMID- 26845894 TI - [EXTENDED PROFUNDAPLASTY]. PMID- 26845895 TI - [WHAT SHOULD JAPAN SURGICAL SOCIETY DO FOR GENDER EQUALITY TO IMPROVE WORK-LIFE BALANCE?]. PMID- 26845896 TI - [ATTEMPTS TO INCREASE SURGEON'S MOTIVATION IN A REMOTE AND SMALL HOSPITAL]. PMID- 26845897 TI - [THE ADVERSE EFFECTS OF CURRENT SUPPORT POLICIES ON THE CAREERS OF FEMALE SURGEONS]. PMID- 26845898 TI - [History of the discovery of viral hepatitis]. PMID- 26845899 TI - [Classification of viral hepatitis]. PMID- 26845900 TI - [The process of development on analysis and diagnosis of hepatitis viruses]. PMID- 26845901 TI - [History and the future on teatment of HCV/HBV hepatitis]. PMID- 26845902 TI - [Hepatitis virus related viruses]. PMID- 26845903 TI - [Final stage in antivirus therapy for HCV patients with chronic liver disease]. PMID- 26845904 TI - [Pathology of viral hepatitis: general remarks]. PMID- 26845905 TI - [HCV replicon]. PMID- 26845906 TI - [Hepatitis virus culture and anti-viral development]. PMID- 26845907 TI - [Development of new therapies using an animal model of hepatitis virus infection]. PMID- 26845908 TI - [Hepatocellular carcinoma animal models]. PMID- 26845909 TI - [Serologic and virologic markers of viral hepatitis]. PMID- 26845910 TI - [Hepatitis C virus infection, its burden and countermeasures from the epidemiological point of view]. PMID- 26845911 TI - [Molecular mechanism of infectious HCV particle production]. PMID- 26845912 TI - [Nucleotide and amino acid polymorphisms associated with efficient replication of Hepatitis C virus]. PMID- 26845913 TI - [Immuno-pathogenesis of HCV infection]. PMID- 26845914 TI - [The mechanism of hepatitis C virus replication]. PMID- 26845915 TI - [Antiviral effect of carnitine for chronic hepatitis or liver cirrhosis patients]. PMID- 26845916 TI - [Inhibitory effect of HCV-NS4B on IFN-lambda induction]. PMID- 26845917 TI - [HCV persistence and HLA-DQB1]. PMID- 26845918 TI - [Rapid automated genotyping of HLA class II gene in patients with hepatitis C virus-related liver disease]. PMID- 26845919 TI - [Impact of IL28B genetic variation on HCV-induced liver fibrosis, inflammation, and steatosis]. PMID- 26845920 TI - [Diagnosis of liver fibrosis in patients with chronic hepatitis using serum enhanced liver fibrosis (ELF)]. PMID- 26845921 TI - [Assessment of the progression grade of liver fibrosis of hepatitis C patients]. PMID- 26845922 TI - [Molecular mechanisms underlying iron metabolic disorder in hepatitis C]. PMID- 26845923 TI - [Mechanism of regulation of HCV replication by miR-122]. PMID- 26845924 TI - [Hepatitis C treatment in consideration of the carcinogenic risk and drug resistant mutations]. PMID- 26845925 TI - [Analysis of interferon-stimulated genes expression associated with early elimination of HCV RNA]. PMID- 26845926 TI - [IL28B genetic variation and hepatic ISGs expression predict treatment efficacy of IFN-based anti-viral therapy for chronic hepatitis C]. PMID- 26845927 TI - [Prediction of anti-viral therapy and host factors]. PMID- 26845928 TI - [Predictive factors of response to Direct Acting Antivirals therapy Drug resistance hepatitis C virus]. PMID- 26845929 TI - [Telaprevir, PEG-IFNalpha-2b and ribavirin combination therapy for difficult to treat patients with genotype 2 chronic hepatitis C]. PMID- 26845930 TI - [Effects of telaprevir (TVR) on cholesterol metabolism]. PMID- 26845931 TI - [Vitamin D supplementation on IFN-based therapy]. PMID- 26845932 TI - [Treatment efficacy and safety in elderly genotype 1b chronic hepatitis C patients with high viral load]. PMID- 26845933 TI - [Diagnosis of hepatitis C with laboratory examinations]. PMID- 26845934 TI - [Non-invasive assessment of liver fibrosis: Ultrasound elastography and MR elastography]. PMID- 26845935 TI - [Management of hepatitis C virus marker]. PMID- 26845936 TI - [Human Mac-2 binding protein glycosylation isomer (M2BPGi), a glycomarker, as a predictor of liver fibrosis for the patients with HCV]. PMID- 26845937 TI - [Pegylated interferon plus ribavirin combination therapy for chronic hepatitis C]. PMID- 26845938 TI - [Telaprevir, peginterferon and ribavirin therapy for chronic hepatitis C]. PMID- 26845939 TI - [A triple combination therapy of simeprevir (SM), pegylated-interferon and ribavirin (PR) with chronic hepatitis C virus genotype 1 infection]. PMID- 26845941 TI - [Daclatasvir plus asunaprevir combination therapy for patients with chronic hepatitis C]. PMID- 26845940 TI - [Vaniprevir with pegylated interferon and ribavirin in treatment for chronic hepatitis C]. PMID- 26845942 TI - [Development status of DAA against hepatitis C]. PMID- 26845943 TI - [Treatment choice of the antiviral agent for the hepatitis C]. PMID- 26845944 TI - [Liver supportive therapy]. PMID- 26845945 TI - [Phlebotomy for chronic hepatitis C]. PMID- 26845946 TI - [Prolonged maintenance therapy by low dose interferon for HCV patients with chronic liver disease]. PMID- 26845947 TI - [Impact of diet & exercise on HCV-infected patients]. PMID- 26845948 TI - [Treatment for hepatitis C under hemodialysis]. PMID- 26845949 TI - [Coinfection of HCV and HIV]. PMID- 26845950 TI - [Treatment for hepatitis C before and after liver transplantation]. PMID- 26845951 TI - [Prevention of recurrence of hepatocellular carcinoma with anti-viral therapy for hepatitis C virus]. PMID- 26845952 TI - [Management of extra-hepatic diseases in chronic viral hepatitis]. PMID- 26845953 TI - [Hepatitis B virus infection, its burden and countermeasures from the epidemiological point of view]. PMID- 26845954 TI - [Introduction to acute hepatitis B]. PMID- 26845955 TI - [Overview and introduction of chronic hepatitis B]. PMID- 26845956 TI - [Fulminant hepatitis B]. PMID- 26845957 TI - [HBV; genes and replication]. PMID- 26845958 TI - [Persistent infection factor of HBV]. PMID- 26845959 TI - [Immunopathogenesis of hepatitis B virus infection]. PMID- 26845960 TI - [Mechanisms of hepatitis B virus replication]. PMID- 26845962 TI - [Hepatitis B virus genotype and the mutation related to clinical outcome]. PMID- 26845961 TI - [HBV entry and its application to the drug development]. PMID- 26845963 TI - [Basic research for HBV-related hepatocarcinogenesis]. PMID- 26845964 TI - [In vivo and in vitro HBV infection model using chimeric mice with humanized livers]. PMID- 26845965 TI - [Nucleic acid pattern recognition for innate sensing of hepatitis B virus (HBV)]. PMID- 26845966 TI - [Immune responses to HBV infection]. PMID- 26845967 TI - [Heterogeneity of HBV genome and its impact on disease progression--Next generation sequencing analysis focusing on preS region and HBsAg titer]. PMID- 26845968 TI - [Integration of hepatitis B virus genome into the host gene: its significance to hepatocarcinogenesis]. PMID- 26845969 TI - [Effects of various soluble factors on the immunopathogenesis of HBV infection]. PMID- 26845970 TI - [Methodology in innate immunity to viral HCC]. PMID- 26845971 TI - [Natural history and prognosis of type B hepatitis]. PMID- 26845972 TI - [Pathogenesis and disease state in hepatitis B virus infection]. PMID- 26845973 TI - [Clinical manifestations of HBV genotypes]. PMID- 26845974 TI - [Genetic factors in HLA-DP associated with pathology, therapeutic outcome, and prognosis of chronic hepatitis B]. PMID- 26845975 TI - [Hepatitis B virus management to prevent reactivation]. PMID- 26845976 TI - [Novel therapeutic drugs GSK548470 (Tenofovir)]. PMID- 26845977 TI - [Long-term administration of nucleos (t) ide analogues and HBV-DNA negativity]. PMID- 26845978 TI - [Seroclearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in hepatitis B virus patients during nucleoside/nucleotide analog therapy]. PMID- 26845979 TI - [Peg-interferon monotherapy and sequential therapy for chronic hepatitis B]. PMID- 26845980 TI - [Efficacy and safety of pegylated-IFN alpha sequential therapy at stopping nucleotide or nucleoside analogues in patients with hepatitis B under the analogue therapy]. PMID- 26845981 TI - [Usefulness of monitoring of M2BPGi during natural course and therapy]. PMID- 26845982 TI - [Basic diagnostic tests and diagnosis]. PMID- 26845983 TI - [HBV related molecular and its clinical significance]. PMID- 26845984 TI - [Clinical utility of hepatitis B virus test marker]. PMID- 26845985 TI - [Management of hepatitis B virus marker]. PMID- 26845986 TI - [Natural course and treatment guideline for chronic HBV infection]. PMID- 26845987 TI - [Peg-interferon therapy for chronic hepatitis B]. PMID- 26845989 TI - [Nucleos (t) ide analogue/interferon sequential therapy for chronic hepatitis B]. PMID- 26845988 TI - [Nucleoside/nucleotide analogue treatment]. PMID- 26845990 TI - [Immunotherapy for chronic hepatitis B]. PMID- 26845991 TI - [Hepatitis B virus e antigen plays an important role in the treatment for chronic hepatitis B]. PMID- 26845992 TI - [Treatments of chronic hepatitis B aiming to HBs seroclearance]. PMID- 26845993 TI - [New antivirals for hepatitis B virus infection]. PMID- 26845994 TI - [Reactivation of HBV due to immunosuppressive and/or anticancer therapies]. PMID- 26845995 TI - [HBV reactivation after liver transplantation and the management strategies]. PMID- 26845996 TI - [Coinfection of HBV and HIV]. PMID- 26845997 TI - [Primary and secondary prevention of HBV-related hepatocellular carcinoma by antiviral treatment]. PMID- 26845998 TI - [Hepatitis B virus infection and its prevention]. PMID- 26845999 TI - [Epidemiology of hepatitis A virus]. PMID- 26846000 TI - [Virological and molecular characteristics of hepatitis A virus]. PMID- 26846001 TI - [Clinical feature of viral hepatitis A]. PMID- 26846003 TI - [Prevention for hepatitis A]. PMID- 26846002 TI - [Diagnosis & treatment for hepatitis A]. PMID- 26846004 TI - [Epidemiology of hepatitis delta]. PMID- 26846005 TI - [Hepatitis D in the past, present and future]. PMID- 26846006 TI - [Diagnosis and treatment of hepatitis D]. PMID- 26846007 TI - [Epidemiology of hepatitis E]. PMID- 26846008 TI - [Virological characteristics of hepatitis E virus]. PMID- 26846009 TI - [Clinical feature in hepatitis E]. PMID- 26846010 TI - [A diagnosis and treatment of the hepatitis E]. PMID- 26846011 TI - [Prevention of hepatitis E virus]. PMID- 26846012 TI - [Hepatitis F virus]. PMID- 26846013 TI - [Hepatitis G virus]. PMID- 26846014 TI - [Etiology and clinical characteristics of hepatitis caused by non-hepatotropic virus]. PMID- 26846015 TI - [Herpes simplex virus]. PMID- 26846016 TI - [EB virus]. PMID- 26846017 TI - [Cytomegalovirus]. PMID- 26846018 TI - [Significance of zinc in hepatitis C]. PMID- 26846019 TI - [Prognostic significance of fibrosis markers in hepatocellular carcinoma among patients with IFN-based therapy]. PMID- 26846020 TI - [Issues of picking up hepatitis virus carriers]. PMID- 26846021 TI - [Vertical transmission]. PMID- 26846022 TI - [IFN therapy in children with chronic hepatitis B]. PMID- 26846023 TI - [Consumption of raw or undercooked meat and hepatitis E]. PMID- 26846024 TI - [Strategy for the prevention of transfusion-transmitted hepatitis--current state of blood donor screening test]. PMID- 26846025 TI - States have the power to solve licensure dilemma. PMID- 26846026 TI - Foul air and (un)fair play? PMID- 26846027 TI - BUILD A BETTER DENTAL TEAM. PMID- 26846028 TI - CDS FOUNDATION CLINIC GETS BACK TO WORK. PMID- 26846029 TI - GUN VIOLENCE. PMID- 26846031 TI - A short brief on conflicts of interest. PMID- 26846030 TI - Having a real estate attorney is a good insurance policy. PMID- 26846032 TI - 'What a Diff'rence a Day Makes'. PMID- 26846033 TI - Changes are coming to the Illinois Dental Practice Act. PMID- 26846034 TI - Try to keep up with Sharon Horwitz. PMID- 26846035 TI - If you have no plan, you have a plan to fail. PMID- 26846036 TI - Surface properties of resin-based composite materials and biofilm formation: A review of the current literature. AB - PURPOSE: To evaluate the state of art on the relations between surface properties (surface roughness, topography, surface free energy and chemistry) of resin-based composite materials and microbial adhesion and biofilm formation. METHODS: An electronic search using Scopus and PubMed (until May 2015) was conducted applying the following search items: "Plaque OR Biofilm AND Surface chemistry", "Plaque OR Biofilm AND Surface-free energy", "Plaque OR Biofilm AND Roughness", "Surface characteristics AND Composites", "Biofilm AND Surface characteristics". RESULTS: Surface properties of resin-based composite materials as well as surface treatments can strongly affect bacterial adhesion and biofilm formation, although the "ideal" surface features have not been identified yet. Moreover, investigations highlighted that cariogenic biofilm formation may alter materials' surface properties, thus encouraging bacterial adhesion and biofilm formation, starting a "vicious cycle" which might compromise restoration longevity. PMID- 26846037 TI - Adhesive sealing of dentin surfaces in vitro: A review. AB - PURPOSE: This review describes the evolution of the use of dental adhesives to form a tight seal of freshly prepared dentin to protect the pulp from bacterial products, during the time between crown preparation and final cementation of full crowns. The evolution of these "immediate dentin sealants" follows the evolution of dental adhesives, in general. That is, they began with multiple-step, etch-and rinse adhesives, and then switched to the use of simplified adhesives. METHODS: Literature was reviewed for evidence that bacteria or bacterial products diffusing across dentin can irritate pulpal tissues before and after smear layer removal. Smear layers can be solubilized by plaque organisms within 7-10 days if they are directly exposed to oral fluids. It is likely that smear layers covered by temporary restorations may last more than 1 month. As long as smear layers remain in place, they can partially seal dentin. Thus, many in vitro studies evaluating the sealing ability of adhesive resins use smear layer-covered dentin as a reference condition. Surprisingly, many adhesives do not seal dentin as well as do smear layers. RESULTS: Both in vitro and in vivo studies show that resin- covered dentin allows dentin fluid to cross polymerized resins. The use of simplified single bottle adhesives to seal dentin was a step backwards. Currently, most authorities use either 3-step adhesives such as Scotchbond Multi Purpose or OptiBond FL or two-step self-etching primer adhesives, such as Clearfil SE, Unifil Bond or AdheSE. PMID- 26846038 TI - Dentin wear after simulated toothbrushing with water, a liquid dentifrice or a standard toothpaste. AB - PURPOSE: To investigate the influence of dentifrices with and without abrasives on the wear and surface topography of human dentin following simulated toothbrushing in vitro. METHODS: 24 dentin specimens were prepared and randomly allocated to a liquid dentifrice (Garglin Gum-Guard), conventional dentifrice (333 Clinic Total Care), and control (distilled water) groups. Specimens were subjected to simulated toothbrushing of 50,000 repeated strokes under a 150 g load. The dentin surface was profiled in each specimen using a profilometer before and after toothbrushing. The mean surface roughness (Ra) of the specimens was calculated and compared by one-way ANOVA and Tukey's post-hoc test (alpha = 0.05). The dentin surfaces were further examined by scanning electron microscopy (SEM). RESULTS: The Ra values were similar between the liquid dentifrice and control groups (P > 0.05), and was significantly higher in the conventional dentifrice group (P < 0.001). On SEM examination, patent dentin tubules were observed in the conventional dentifrice and liquid dentifrice groups, but were not observed in the control group. PMID- 26846039 TI - Evaluation of two disinfection/sterilization methods on silicon rubber-based composite finishing instruments. AB - PURPOSE: To evaluate the effectiveness of disinfection/sterilization methods and their effects on polishing capacity, micomorphology, and composition of two different composite fiishing and polishing instruments. METHODS: Two brands of finishing and polishing instruments (Jiffy and Optimize), were analyzed. For the antimicrobial test, 60 points (30 of each brand) were used for polishing composite restorations and submitted to three different groups of disinfection/sterilization methods: none (control), autoclaving, and immersion in peracetic acid for 60 minutes. The in vitro tests were performed to evaluate the polishing performance on resin composite disks (Amelogen) using a 3D scanner (Talyscan) and to evaluate the effects on the points' surface composition (XRF) and micromorphology (MEV) after completing a polishing and sterilizing routine five times. RESULTS: Both sterilization/disinfection methods were efficient against oral cultivable organisms and no deleterious modification was observed to point surface. PMID- 26846040 TI - Efficacy of different "in-office" desensitizing treatment methods: An in vitro SEM analysis. AB - PURPOSE: To evaluate, in vitro, the obliteration of dentin tubules promoted by different desensitizing methods, before and after pH cycling. METHODS: Human dentin blocks of 4x4 mm were randomly divided into: control group (n = 20): no treatment; Group GH (n = 20): surface treatment with a solution containing glutaraldehyde (5.1%), HEMA (36.1%), sodium fluoride (NaF), and deionized water; Group NP (n = 20): surface treatment with a calcium phosphate gel containing nanostructured hydroxyapatite crystals, NaF and NK; and Group ARG (n = 20): surface treatment with a paste containing CaCO3 and 8% arginine. After treatment, 10 samples of each group were evaluated in scanning electron microscopy (SEM) while another 10 were included in a pH cycling procedure for 48 hours, and then analyzed in the SEM. All SEM images were evaluated by three calibrated examiners regarding dentin tubular obliteration. Mann-Whitney and Kruskal-Wallis tests were used for data analysis (P < 0.05). RESULTS: The GH, NP, and ARG groups promoted immediate obliteration higher than the control group (P < 0.05) with NP and ARG groups superior to GH group (P < 0.05). After pH cycling, an increase in tubular obliteration in the GH group was observed, which was similar to the NP and ARG groups (P > 0.05), even though all groups promoted higher obliteration than the control group (P < 0.05). All treatments were effective in a tubular obliteration. PMID- 26846041 TI - Effect of sonic vibration of an ultrasonic toothbrush on the removal of Streptococcus mutans biofilm from enamel surface. AB - PURPOSE: To evaluate in vitro the effect of sonic vibration of an ultrasonic toothbrush in the removal of Streptococcus mutans (S. mutans) biofilm from human enamel. METHODS: S. mutans dental biofilm was formed in vitro on human enamel blocks coated by salivary pellicle. The blocks were incubated with a suspension of S. mutans at 37 degrees C for 24 or 72 hours. The blocks were divided to one of three conditions according to the different toothbrush action modes: ultrasound plus sonic vibration (U+SV), ultrasound-only (U) and no ultrasound and no sonic vibration (control). Samples were exposed to each mode for 3 minutes with the toothbrush bristles placed 5 mm away from the enamel block surface. The samples were observed by scanning electron microscopy (SEM) and quantification of S. mutans was performed. RESULTS: U+SV showed lower bacterial counts compared to U and control on the 72 hour-biofilm (P < 0.05). The SEM analysis revealed that U+SV and U disrupted the S. mutans chains in the 24- and 72-hour biofilm. PMID- 26846042 TI - Randomized controlled trial comparing a powered toothbrush with distinct multi directional cleaning action to a manual flat trim toothbrush. AB - PURPOSE: To compare the plaque and gingivitis efficacy of a power toothbrush with distinct multi-directional cleaning action (Colgate(r) ProClinical(r) A1500 Power Toothbrush) against a manual flat-trim toothbrush (Oral-B Indicator). METHODS: This randomized control trial was a single-center, examiner-blind, parallel group, design and assessed plaque removal after a single brushing, as well as plaque removal and gingivitis reduction after 4 weeks and 12 weeks of brushing. Qualifying subjects used their assigned toothbrush to brush their teeth under supervision after which they were evaluated for plaque (post-brushing). Over the next 12 weeks, subjects brushed unsupervised at home with their assigned toothbrush. After 4 weeks and 12 weeks, subjects returned to the center for plaque and gingivitis examinations. RESULTS: 80 subjects were screened for eligibility and randomized into the study. 79 subjects completed the study. Both toothbrushes provided statistically significant reductions in all plaque index scores at all time points in comparison to the pre-brushing scores. After 4 weeks and 12 weeks, statistically significant reductions in gingivitis and gingivitis severity scores were observed for subjects using the power toothbrush, whereas statistically significant increases in gingivitis and gingivitis severity were observed for subjects using the manual toothbrush. In conclusion, relative to the manual toothbrush, the power toothbrush provided statistically significantly (P < 0.05) greater removal of plaque: whole-mouth (131%), gumline (97.4%), and interproximal (220%), as well as reductions in gingivitis (400%), and gingivitis severity (320%) after 12 weeks of use. Compared to the manual flat-trim toothbrush, the power toothbrush with distinct multi-directional cleaning action demonstrates statistically and clinically significantly greater levels of plaque removal and gingivitis reduction at all time points. PMID- 26846044 TI - Influence of organic acids present in oral biofilm on the durability of the repair bond strength, sorption and solubility of resin composites. AB - PURPOSE: To evaluate the repair bond strength after storage in water, lactic and propionic acid after 7 days and 6 months and the sorption and solubility of resin composites used. METHODS: Five cylinders of each resin composite (microhybrid, nanofilled and silorane-based composite) were prepared. Specimens were aged with thermocycling (5 and 55 degrees C) 5,000 times. A repair procedure was performed using intraoral sandblasting with 50-um aluminum oxide, application of an adhesive system and cylinder of composite was fabricated. Specimens were sectioned into beams and stored in three immersion media: water, propionic acid and lactic acid. The microtensile bond strength was measured after periods of 7 days and 6 months. Sorption and solubility were evaluated using 15 specimens (0 = 6 mm; h = 1 mm) of each resin composite, which were prepared and assigned into three groups (n = 5) according to the immersion media (water, propionic acid and lactic acid). Data were analyzed using one-way/two-way/three-way ANOVA and Tukey's test (alpha = 0.05). RESULTS: The resin composites, immersion media and time of immersion did not affect the repair bond strength (microhybrid 38.3 to 40.9 MPa; nanofilled 38.7 to 42.2 MPa; silorane 41.2 to 51.1 MPa). Additionally, the immersion media did not affect the sorption and solubility. The silorane based composite presented the lowest sorption (10.5 to 12.1 ug/mm3) and solubility (-2.4 to -2.7 ug/mm3), while the nanofilled methacrylate-based composite showed the highest sorption (32.1 to 33.6 ug/mm3). Regarding solubility, the nanofilled and microhybrid methacrylate-based composites did not present statistically significant differences. PMID- 26846045 TI - Kicking Off Our 35th Year. PMID- 26846043 TI - Two pre-treatments for bonding to non-carious cervical root dentin. AB - PURPOSE: To investigate the effect of airborne-particle abrasion or diamond bur preparation as pre-treatment steps of non-carious cervical root dentin regarding substance loss and bond strength. METHODS: 45 dentin specimens-produced from crowns of extracted human incisors by grinding the labial surfaces with silicon carbide papers (control) were treated with one of three adhesive systems (Group 1A-C; A: OptiBond FL, B: Clearfil SE Bond, or C: Scotchbond Universal; n= 15/adhesive system). Another 135 dentin specimens (n = 15/group) produced from the labial, non-carious cervical root part of extracted human incisors were treated with one of the adhesive systems after either no pre-treatment (Group 2A C), pre-treatment with airborne-particle abrasion (CoJet Prep and 50 um aluminum oxide powder; Group 3A-C), or pre-treatment with diamond bur preparation (40 um grit size; Group 4A-C). Substance loss caused by the pre-treatment was measured in Groups 3 and 4. After treatment with the adhesive systems, resin composite was applied and all specimens were stored (37 degrees C, 100% humidity, 24 hours) until measurement of micro-shear bond strength (uSBS). Data were analyzed with a nonparametric ANOVA followed by Kruskal-Wallis and Wilcoxon rank sum tests (level of significance: alpha = 0.05). RESULTS: Overall substance loss was significantly lower in Group 3 (median: 19 um) than in Group 4 (median: 113 um; P < 0.0001). There were no significant differences in uSBS between the adhesive systems (A-C) in Group 1, Group 3, and Group 4 (P 0.133). In Group 2, OptiBond FL (Group 2A) and Clearfil SE Bond (Group 2B) yielded significantly higher uSBS than Scotchbond Universal (Group 2C; P <= 0.032). For OptiBond FL and Clearfil SE Bond, there were no significant differences in uSBS between the ground crown dentin and the non-carious cervical root dentin regardless of any pre-treatment of the latter (both P = 0.661). For Scotchbond Universal, the uSBS to non-carious cervical root dentin without pre-treatment was significantly lower than to ground crown dentin and to non-carious cervical root dentin pre-treated with airborne-particle abrasion or diamond bur preparation (P <= 0.014). PMID- 26846046 TI - Focus On: Implants. PMID- 26846048 TI - Comfortably Numb. PMID- 26846047 TI - Innovations in Patient Relationships and Communication: "Changing the Story, One Patient at a Time". PMID- 26846049 TI - Evolution of Comprehensive Care, Part 6: Aesthetics, Veneers, and Whitening. PMID- 26846050 TI - "My Best Handpiece". PMID- 26846051 TI - To Sugar or Not to Sugar: With Soft Drinks, It Makes No Difference; They Are All Bad. PMID- 26846052 TI - Study: Cognitive Behavioral Therapy Helps Reduce Patients' Dental Phobia. PMID- 26846053 TI - Australia Considers a Future of "No-Drill" Dentistry: Results of Seven-Year Study Confirm Benefits of Preventative Oral Care. PMID- 26846055 TI - Delight Your Patients With a 45-Minute Smile Rehab. PMID- 26846056 TI - Single-File Shaping Technique: Achieving a Gold Medal Result. PMID- 26846057 TI - Dental Implants in the Aesthetic Zone. PMID- 26846058 TI - Guided Gingival Growth: Improving Aesthetics During Second-Stage Surgery. AB - GGG is a conservative, efficient, and relatively straightforward treatment for mild soft-tissue deficits. When applied within its limitations, it may be a valuable tool for aesthetic refinement around dental implants. PMID- 26846059 TI - Technology to Control Excessive Occlusal Contact Force: Enhancing Implant Restoration Longevity. PMID- 26846060 TI - Achieving Anterior Aesthetics in a Full-Arch Implant Case. AB - The proper approach to achieving the best possible smile for any aesthetic case must start with a full-smile analysis. Only when the practitioner determines the ideal final position of the teeth can the restorative phase begin. In this case, using provisional restorations and a transferable wax-up resulted in a final restoration that yielded optimal aesthetics, excellent function, and a very satisfied patient. PMID- 26846061 TI - Digital Design: Predictability, Profitability, and Efficiency. PMID- 26846062 TI - Vhy GPs Should Pursue Orthodontic Training. PMID- 26846063 TI - Composite Versus Ceramics, Part I: Young Patients and Fractures. PMID- 26846064 TI - The Relationship Between Periodontics and Cardiovascular Disease. PMID- 26846066 TI - Coordinating advocacy efforts for hospitals. PMID- 26846065 TI - Diesel Emissions and Lung Cancer: An Evaluation of Recent Epidemiological Evidence for Quantitative Risk Assessment. PMID- 26846067 TI - Alert system improves staff assistance. PMID- 26846068 TI - ECONOMIES OF SCALE. Large hospital projects aim for increased efficiency and consolidated services. PMID- 26846069 TI - Unlocking- facilities data. Measuring building performance over a real-estate portfolio. PMID- 26846070 TI - Ambulatory environments. Eight ways hospitals are reaching out into their communities. PMID- 26846071 TI - Barriers to entry. Advanced access-control technologies protect against external threats. PMID- 26846072 TI - Hot topics in codes and standards. Physical environment issues to monitor in the new year. PMID- 26846073 TI - Facility-specific pest management. Tailoring procedures for different off-site health care facilities. PMID- 26846074 TI - [Psychosomatic Aspects of Bronchial Asthma in Children]. AB - Bronchial asthma is the most common chronic disease in children affecting 30% of the child population. The purpose of this review was to analyze and summarize the works offoreign and Russian authors who evaluated the impact of mental disorders on the course of asthma in children. The article presents the definition of asthma as a psychosomatic disease and relevance of the study against this background. The authors adduce the results of research studies which allow us to estimate the interaction between the degree of anxiety, accentuation of the nature, severity of asthma, and the duration of the disease. The existing publications demonstrate that the researchers' opinions are polarized regarding the cause-and-effect relationship between psychological disorders and controlled asthma. The authors came to a conclusion that early detection ofpsychopathological symptoms and appropriate psychotherapeutic administration would improve the efficacy of treatment in children with bronchial asthma and the social adaptation, adjust the system offamily relations, and have a positive effect on the course of the disease. PMID- 26846075 TI - [Thyroid Adenomas in Children]. AB - According to the papers thyroid nodules are quite rare in the first two decades of life. However, there are some exceptions, relating to areas with an iodine deficiency or affected by radioactive fallout, where the risk of nodules and carcinomas is increased. Therefore, it is a great challenge for the physician to distinguish between benign and malignant lesions preoperatively, and not only in these areas of greater risk. The authors analyzed current works, which are devoted to diagnostics and treatment of adenomas of thyroid gland in children. This literature review is based on works dedicated to epidemiology, histotypes study, and methods of diagnostics, surgical treatment, prognosis and complications of this pathology. The current tendencies in surgical approaches, intraoperative monitoring of recurrent laryngeal nerve are also discussed. The actuality of this problem is connected with last decade increase of adenomas in structure of thyroid gland nodules, increase of number of patients with multiple adenomas and with polypathias: adenomas with nodular goiter, autoimmune thyroiditis and cancer in children. The difficulties of diagnostic of adenomas are related to the similar clinical symptoms, cytogenetic characteristics of growth of benign and malignant lesions of thyroid gland. Additionally there is no systematic review about thyroid adenomas in children recent years. PMID- 26846076 TI - [The Study of Psychological Characteristics of Children and Adolescents with Digestive Diseases]. AB - OBJECTIVE: The present study was aimed at the psychological characteristics of children with different chronic diseases of the digestive system and the identification of key factors influencing the formation of their personality. METHODS: The continuous prospective study of psychological peculiarities of 125 patients (7-17 y.o.) with diseases of the digestive system who have been monitored at Scientific Centre of Children's Health (Moscow) was performed. As research methods were used: analysis of medical and pedagogical documentation, participant observation, educational experiment, interview, questionnaires and projective methods. RESULTS: The study involved 125 patients aged 7-17 years (12.4 averagely) with diseases of the digestive system including teens--68 (54%), primary school pupil--57 (46%). The number of boys significantly prevailed over the number of girls (2:1). The study confirmed the existence of a close relationship and mutual influence of three factors: the physical condition, social situation of development, and individual psychological characteristics of children. According to the psychological characteristics the children can be combined in three groups: Group I (47 of 125 people; 37.6%) - children with bad psychological status. This is most typicalfor children with active form of chronic diseases requiring intensive medical assistance (37 of 47people; 78.7%). Group II (59 of 125 people; 47.2%)--children with instable psychological condition, with risk of neurotization. This group mainly comprises patients with chronic diseases at the stage of unstable clinical remission with preserved or compensated functions of organism bodies and systems or with incomplete compensation of functions requiring long term supportive treatment (45 of 59 people; 76.3%). Group III--patients with rather stable psychological condition (19 of 125 people; 15.2%). It comprises patients with rather stable psychological condition, anyway, with expressed psychological vulnerability in stress situation. Most children suffer from chronic diseases of different etiology at the stage of clinical remission with rare aggravations, with preserved or compensated functions, provided there are no aggravations of the basic disease (17of 19 people; 89.5%). CONCLUSION: Most children with diseases of the digestive system have the psychological difficulties, while their identity is often formed in the distorted social conditions. Therefore, these children need psychological and pedagogical support, as well the special psychological and pedagogical conditions for the realization of their mental and cognitive capacities. To put together a program of psychological and educational assistance we should take into account the child's age at the moment of occurrence of the disease, etiology, duration and severity of the illness, the nature and degree of non compliance of social environmental. PMID- 26846077 TI - [Vitamin D--A New Vector of Cancer Prevention?]. AB - Currently, a great number of research projects are focused on finding new treatment methods for cancer and carcinogenesis predictors, as well as the ways to dicrease cancer development risks. This article provides an overview of research on vitamin D as cancer prevention factor. The results of independent experiments and in vitro tests explaining the mechanisms of protective effect of vitamin D and its derivatives on cancer are illustrated. The review of epidemiological survey results obtained from different countries and various populations that were focused on the association of vitamin D use with various cancer pathologies incidence was performed. PMID- 26846078 TI - [Clinical and Immunological Features of Infectious Complications in Patients with Multiple Myeloma]. AB - BACKGROUND: Infectious complications--the leading cause of mortality in patients with multiple myeloma (MM), their appearance is regarded as an adverse prognostic factor in the course of the disease. OBJECTIVE: The aim of our study was to evaluate the clinical and immunological features of infectious complications in patients with G-immunochemical MM to find the most informative indicators in their forecasting. METHODS: A randomized controlled trial was made. All patients were divided into 3 groupsfor comparison: Group 1 (n = 47)--MM patients, G immunochemical variant with infection, Group 2 (n = 54)--MM patients, G immunochemical option no infectious complications, and Group 3 (n = 125)--healthy volunteers. Research material was deoxygenated blood taken on admission of a patient to the hematology department before the pathogenetic treatment. Identification of G-variant was carried by immunofixation and electrophoresis. The immune status was assessed by indirect immunofluorescence. The concentration of IgA, M, E and G, and the levels of IL 2, IL 4, IL 8, TNFalpha, IFNgamma in serum was determined by enzyme immunoassay. The activity of neutrophil granulocytes (NG) was studied by chemiluminescent analysis of spontaneous and induced production of reactive oxygen species. Statistical analysis was performed using the software STATISTICA v. 8.0 (USA), RESULTS: We analyzed data from 101 patients with MM and 125 healthy volunteers. The average age of MM patients was 60.53 +/- 6.78 years. The group of healthy volunteers was similar in sex and age to groups of patients with MM. In patients with MM in the presence of infectious complications the researchers detected combined secondary development of T and B cell immunodeficiency, changes in non-specific immunity depended on the stage of the disease, unidirectional irregularities in spontaneous and induced chemiluminescence activity NG in II stage disease and multidirectional irregularities in stage III (p = 0.045). Prevalence of the content of proinflammatory cytokines on inflammatory (p < 0.001) and the deviation of the immune response to Th1-type were detected. CONCLUSION: the set of 6 informative indicators (the content of IL 4, IL 2, TNF alpha, IgG, the absolute number of CD4+ and CD19+ cells) enables the development of prediction method of infectious complications in patients with MM. PMID- 26846079 TI - [Epigenetic Aspects of Osteoporosis]. AB - This review describes the epigenetic regulation of osteoblastogenesis and osteoclastogenesis and its future implementation in the diagnosis and treatment of osteoporosis. A considerable part of the review is dedicated to the microRNAs (miRNAs). miRNAs are small regulatory factors that regulate gene expression, by post-transcriptional regulation of genes playing an important role in numerous cellular processes, including cell differentiation and apoptosis. Recently, a number of studies have revealed that miRNAs participate in bone homeostasis and their role in the pathogenesis of osteoporosis is practically evident. In this review, we highlight the miRNAs involved in bone remodelling and their roles in osteoporosis. miRNAs are stable molecules which make them promising potential markers for bone remodeling and osteoporosis. PMID- 26846080 TI - [Mathematical Modeling of the Blood Glucose Regulation System in Diabetes Mellitus Patients]. AB - Interest in the mathematical modeling of the carbohydrate metabolism regulation system increases in recent years. This is associated with a "closed loop" insulin pump development (it controls an insulin infusion depending on the blood glucose level). To create an algorithm for the automatic control of insulin (and other hormones) infusion using an insulin pump it is necessary to accurately predict glycaemia level. So, the primary objective of mathematical modeling is to predict the blood glucose level changes, caused by the wide range of external factors. This review discusses the main mathematical models of blood glucose level control physiological system (simplified insulin-glucose system). The two major classes of models--empirical and theoretical--are described in detail. The ideal mathematical model of carbohydrate metabolism regulatory system is absent. However, the success in the field of blood glucose level control modeling and simulating is essentialfor the further development of diabetes prevention and treatment technologies, and creating an artificial pancreas in particular. PMID- 26846081 TI - [In vitro Cultivation of Functioning Passaged Ciliated Epithelium for Trachea Tissue Engineering]. AB - BACKGROUND: Currently all tissue engineered trachea transplants had no ciliated epithelium until transplantation, and long-term temporary lack of mucociliary clearance leads to patients' condition decline and reduced life quality in postoperative period. So, the need for a better cultivation method and studying ciliated epithelium growth characteristics in cell culture increased rapidly. OBJECTIVE: The aim of our study was to investigate cultivation offunctionally complete passaged ciliated epitheliumfor trachea tissue engineering. METHODS: Human ciliated epithelium isolated from intraoperative bioptate was used for culturing in the special complex medium with morphological and functional characteristics evaluation. RESULTS: Ciliated epithelial cell-groups were obtained by culturing in the special complex medium. Generated cell-groups had ciliary activity and showed well-coordinated movement with functional characteristics similar to native epithelial tissue. The basic parameters of cell activity were studied. CONCLUSION: Thus our study provides a new insight for the problem of ciliated epithelium in vitro culturing as well as developing the optimal laboratory method. PMID- 26846082 TI - [Natriuretic Peptides: Role in Current Cardiology]. AB - Natriuretic peptides were discovered in 50-70s of the XX century. BNP was more diagnostically and prognostically significant, as it is secreted directly into the ventricles of the heart. The studies demonstrated a high predictive value of increasing the level of BNP in acute decompensation of heart failure and in patients with chronic heart failure in a study of Val-HeFT It was demonstrated that monitoring the level of NT-proBNP can be used for the selection of optimal therapy, affect the course and outcome of the disease, and reduce the cost of treatment. The next step in learning BNP was to undertake attempts of their use in the therapy of heart failure. Long-term therapy BNP (drug nesiritide) improved left ventricular remodelling in patients with stable heart failure. Currently the definition of the levels of BNP and NT-proBNP is used for the diagnosis and management of patients with heart failure. PMID- 26846083 TI - [Phylodynamic of HCV Populations]. AB - Hepatitis C virus is an actual public health problem worldwide since its discovering in 1989. It is explained not only by the wide spreading and frequent adverse outcomes of disease, the lack of effective preventive vaccine, but also by the high genetic variability of the virus. The current review summarizes the results of phylodynamic and phylogeographic studies of different HCV populations that allowed to characterize epidemic processes, to analyze the divergence of HCV into genotypes and subtypes, and to determine the geographic origin of the current HCV epidemic variants. PMID- 26846084 TI - [Causes and Factors of Male Infertility]. AB - The preservation of reproductive health of the population is an important factor of demographic policy of the state. According to some authors from 14 to 30% of couples of reproductive age suffer from infertility, malefactor in such marriages is detected in more than half of the cases. As you know, in recent years there has been a significant deterioration in the main indicators of reproductive function of men. Increased the number of andrological diseases, morphological disorders of the male reproductive system, almost halved the production of sperm in men of reproductive age. The reason probably lies behind a whole range ofstressfactors, such as medical ignorance, uncontrolled and inappropriate use of medication, metabolic disturbances, lack of vitamins and minerals, the impact of industrial pollutants, as well as the growth of addictive disorders (alcoholism, smoking and drug addiction). The forms of infertility differ according to its etiology and severity from minor changes to complete spermatogenesis dysfunction of the gonads, and can also occur due to genetic disorders. The lack of analysis of the relationship between clinical and genetic-biochemical components in men with infertility makes it impossible to understand the pathogenesis of infertility and to assess the risks of male infertility. High level of current medicine does not always guarantee an identification of the cause of male infertility. The article analyzes data from the review of specialized literature on the diagnosis and etiopathogenesis of male infertility. Frequency and clinical signs of pathology of the male reproductive system depend on the combinatorial effects of environmental influences, manifested most often in mutually reinforcing effect. A combination of several, seemed to be imperceptible factors makes the risk of development of male reproductive pathology very high. This situation compels specialists to conduct comprehensive studies on the men reproductive potential. PMID- 26846085 TI - [Gender Differences of Behavioral Risk Factors in Saint-Petersburg Inhabitants]. AB - BACKGROUND: In developed countries there are significant gender differences in lifetime expectancy that can be explained by behavioral risk factors (RF). OBJECTIVE: The aim of our study was to estimate gender features of behavioral RF in general population of Saint-Petersburg, Russia. METHODS: As a part of all Russian epidemiology survey ESSE-RF a random sampling of 1600 Saint-Petersburg inhabitants (25-64 y.o.) stratified by age and sex was performed. All participants filled in the questionnaire. Anthropometry (weight, height, body mass index (BMI), waist circumference (WC) and fasting blood-tests (lipids, glucose by Abbott Architect 8000 (USA)) were performed. RESULTS: There were examined 573 (36%) men and 1027 (64%) women. No gender differences in obesity were found according to BMI criteria--in 178 (31.2%) women and 352 (35.1%) men. Obesity was more often detected in females according to WC criteria: ATPIII--44.1 vs 30.3%; IDF 51.2 vs 66.4% (p < 0.001 for both). Linear regression analysis was performed and age was associated with BMI--1.6 kg/m2/decade, WC in women--5.2 cm/decade and WC in men--2.8 cm/decade, p < 0.001 for all anthropometric parameters. Optimal level of physical activity was equally documented in both genders--540 (61.2%) women and 286 (58.9%) men. Daily intake of sweets was lower in men--228 (39.8%) vs 539 (52.5%) in women (p < 0.001). 810 (50.6%) of trial subjects were non-smokers, 395 (24.7%) were former smokers, and 395 (24.7%) were smokers at the moment of trial. The higher number of female smokers was observed- 194 (19.1%). CONCLUSION: A high prevalence of obesity is observed in sample of Saint-Petersburg inhabitants--it is higher among women according to WC criteria regardless of menopause, possibly due to bigger sweets consumption. Males smoke more often and consume less fresh fruits and vegetables which is accompanied by a higher prevalence of hyperglycemia and hypertriglyceridemia. PMID- 26846086 TI - [Morphofunctional Changes of Spleen After Hemostasis by Nonequilibrium Plasma]. AB - BACKGROUND: Heavy bleeding is developed in case of spleen injury. It often leads to death. At present the search and development of new methods for hemostasis of spleen bleeding continues. An innovative method is coagulation of nonequilibrium plasma. OBJECTIVE: Our aim was to study the effect of nonequilibrium plasma on the morphofunctional state of the spleen. METHODS: The non-randomized study by type of "case-control" was conducted. The experiment was carried out on 45 male rabbits weighing 3000-3200 g. 1st group (control; n = 5)--intact animals without surgery; 2nd group (experimental, n = 40)--animals after atypical resection of the spleen and hemostasis by nonequilibrium plasma. The volume of blood loss, FBC, histological data, splenogram analysis data were assessed at defined periods (60 min, 3rd, 5th, 7th, 14th, 30th, 90th, 180th days) after surgery. They were compared with data of the control group. RESULTS: The volume of blood loss during the resection of the spleen with hemostasis by nonequilibrium plasma was 16.6 [15.98; 17.22] ml. Increase of neutrophil to 38 [24; 39] (control group 17[13, 18], p = 0.009), monocytes to 15 [14, 18] (control group 8 [6, 11], p = 0.036) is revealed in the FBC in the early period after hemostasis with nonequilibrium plasma. It is reduced to the norm on 30 day. Histological examination revealed leukocyte infiltration, edema, microvascular stasis, dilatation of vessels in the early period. At long-term period structure of the organ is normalized. Splenogramm analysis revealed a statistically significant (p = 0.023) decrease in the relative number of small lymphocytes by 28% in animals after hemostasis with nonequilibrium plasma as compared to control (23.3 [179; 26.7] versus 30.8 [29.25; 34.3] respectively). CONCLUSION: treatment of bleeding surface by plasma flow for 1.5-2 min is required order to achieve effective hemostasis during surgery of spleen injuries in the experiment. After coagulation there is minimal damage of the spleen parenchyma, which manifests itself as activation reaction. At long-term period parenchyma ofthe spleen completely regenerates with theformation of cicatrical tissue that does not affect thefunctioning of organ. PMID- 26846087 TI - [Pathogenetic Relationship between Endothelial Dysfunction and Disorders of Blood Coagulation Potential in Pregnancy Complicated by Pre-Eclampsia]. AB - Until now, there is no systematic information on the role of endothelial dysfunction in the mechanisms of disorders of blood coagulation potential and microcirculation in different organs and tissues in preeclampsia. OBJECTIVE: Our aim was to extend the existing principles of diagnosis of pre-eclampsia by establishing the role of endothelial dysfunction in the mechanisms of blood coagulation potential violations. METHODS: A prospective comparative study was performed. Condition of coagulation processes studied by conventional techniques, parameters of a functional endothelium (nitric oxide metabolites, endothelin 1, thrombospondin, thrombomodulin and intercellular adhesion molecules in blood plasma)--by ELISA. RESULTS: The study group included 55 patients with moderate preeclampsia and 49 pregnant women with severe pre-eclampsia, in the control group--40 women with physiological pregnancy. In patients with pre-eclampsia moderate observed increase in plasma endothelin-1 (p < 0.001), thrombospondin (p < 0.001), intercellular adhesion molecules (p < 0.001) while reducing the level of nitrogen oxide (p < 0.001), increase in time of fibrinolysis (p < 0.050) and decreased international normalized ratio (p < 0.050) compared with the control group. With increasing severity of preeclampsia the researchers detected in blood plasma of patients a progressive increase in endothelin 1 (p1 < 0.020), thrombospondin (p1 < 0.001), intercellular adhesion molecules (p1 < 0.001) and decrease of nitric oxide metabolites (p1 < 0.001) and thrombomodulin (p1 < 0.001); the last combined with the activation of procoagulant hemostasis. CONCLUSION: There is a pathogenetic relationship between the development of endothelial dysfunction, impaired blood coagulation potential and the severity of clinical signs ofpreeclampsia. To widen the number of existing techniques to diagnose the severity of pre-eclampsia we recommende to mesure endothelin 1, thrombomodulin, thrombospondin, intercellular adhesion molecules and nitric oxide metabolites in the blood plasma, and use traditional indicators to assess the hemostatic system. PMID- 26846088 TI - [Condition of State and Trait Anxiety in Pregnant Women with Fetal Malformations]. AB - OBJECTIVE: Our aim was to assess the level of state and trait anxiety, and the level of tolerated stress in pregnant women with fetus malformations. METHODS: A controlled non-randomized clinical study with sequential inclusion of participants was carried out. Psychoemotional status of pregnant women was assessed by Spielberger anxiety scale, with identification of state and trait anxiety, as well as on the basis of medical history data. Pregnant women were divided into 2 groups. Control group--20 women with physiological gestation course without any fetus malformations and absence of stress situations in medical history. Main group--40 women with fetus malformations, presence of long stressful situations in medical history, starting from early gestation period. RESULTS: 60 women aged 20-37 years old, at the pregnancy age of 20-38 weeks were examined by ultrasound with assessment anatomy of thefetus. Comparative analysis of the psychological and emotional status of pregnant women from both groups indicated significant increase of the state and trait anxiety level in the main group of women compared to the control in the average grew from 30.80 +/- 1.47 to 48.13 +/- 3.84 (p < 0.001) and from 32.35 +/- 1.45 to 50.25 +/- 3.40 (p < 0.001) respectively. CONCLUSION: The identified high level of state and trait anxiety in pregnant women with fetus malformations allows concluding that maternal stress is a potential risk factorfor generation of intrauterine malformations of the fetus. This serves as a basis to recommend corresponding prophylactic, anti-stress measures should be taken during such pregnancy, especially at early stages, when fetus tissues formation process is taking place. PMID- 26846089 TI - [Interneurons Brainstem of the Human]. AB - OBJECTIVE: To conduct a comparative study of the structural organization of internuclear interneurons involved in the metabolism of nitrogen monoxide, hydrogen sulphide and carbon monoxide in the caudal brain stem humans. METHODS: The cross-sectional study was performed. We used histochemical and immunohistochemical methods to study the internuclear interneurons expressing neuronal nitric oxide synthase, cystathionine beta-synthase and heme oxygenase-2 which are located between the giant and small cell reticular nuclei (cell group 1), small cell reticular nucleus and the nucleus of the solitary tract (cell group 2) or is surrounded by reticular lateral nucleus (cell group 3). RESULTS: The work was carried out on the corpses of 6 men 18-44 years old who died from causes unrelated to the damage of the central nervous system. We revealed the differences between internuclear organization and intranuclear interneurons and local structural features of internuclear interneurons that are more clearly visible between the cell group 1 including a relatively large number of large neurons and cell groups 2 and 3 (p < 0.001). In the latter two groups small cells with high concentrations of the neuronal nitric oxide synthase and heme oxygenase 2 dominated. CONCLUSION: Despite the fact that the number of internuclear interneurons significantly is less than the number of intranuclear cells, they have structural prerequisites to control integration processes in the brain. Internuclear interneurons produce gasotransmitters and classical mediators of nerve impulse, form a local chain of interneurons between vasomotor nuclei, share many links with the above and the lower parts of the brain. PMID- 26846090 TI - Gualou Xiebai decoction inhibits cardiac dysfunction and inflammation in cardiac fibrosis rats. AB - BACKGROUND: Gualou Xiebai Decoction (GXD) is a well-known traditional Chinese recipe. It has been used to treat cardiovascular disorders for nearly two thousand years. But there is a lack of reports on cardiac fibrosis and underlying mechanism. METHODS: Myocardial infarction was performed by ligation of left anterior descending coronary artery (LAD) in male Wistar rats. Rats with myocardial infarction were treated with GXD (1.14 g/kg, 4.53 g/kg) daily for 4 weeks. Cardiac function was evaluated by echocardiography. Hemodynamic parameters and infarct size were measured in each group. Myocardial enzymes were examined by biochemical tests. Inflammatory cytokines were assessed by ELISA, and interrelated proteins were detected by western blot. RESULTS: Cardiac function was significantly improved in GXD-treatment rats after myocardial infarction (MI), which was accompanied with decreased infarct size. Administration of GXD to myocardial fibrosis rats significantly ameliorated the activities of AST, LDH and CK-MB in serum. The increase in inflammatory factors (TNF-alpha, IL-1beta) were markedly reduced upon GXD treatment. Furthermore, the inflammatory mediators (NF kappaB p65, TNF-alpha, MCP-1) were down-regulated by GXD in the myocardial fibrosis rats. CONCLUSIONS: Treatment with GXD improved cardiac function induced by myocardial fibrosis by inhibiting expression of inflammatory mediators associated with NF-kappaB. PMID- 26846092 TI - Circulation of avian paramyxoviruses in wild birds of Kazakhstan in 2002-2013. AB - BACKGROUND: Screening wild birds for avian paramyxoviruses is of increasing importance. 6913 samples of tracheal and cloacal swabs were collected during 2002 2013 and tested to study the prevalence of APMVs in wild avifauna of Kazakhstan. As a result, 45 isolates were obtained during this period and their ecological niches and genetic relationships were defined. METHODS: Tracheal and cloacal samples from wild birds were collected using sterile swabs placed in viral transport medium and kept in liquid nitrogen until delivery to the laboratory. Samples were inoculated into 10-day-old embryonated chicken eggs and reverse transcription PCR (RT-PCR) assays were performed via a one-step protocol. The PCR products were sequenced and phylogenetic trees were constructed using the 'Neighbour Joining' method. RESULTS: Six thousand nine hundred thirteen samples from 183 bird species were investigated and 45 isolates belonging to four different serotypes APMV-1, APMV-4, APMV-6 and APMV-8 were identified. All APMVs were isolated predominantly from birds belonging to Anatidae family (ducks and geese) and only one APMV-4 isolate was obtained from shorebird (Curlew) on the Caspian seashore. Genetic studies showed that the recovered APMV-1 strains had highest homology with European isolates. APMV-4 strains isolated in 2003, and APMV-6 and APMV-8 isolated in 2013 were 99 % identical to isolates from Far East. CONCLUSION: This is the first reported characterization of avian paramyxoviruses from wild birds isolated in Kazakhstan. These data confirm the wide distribution of APMV-1, APMV-4 and APMV-6 in the Asian subcontinent. The obtained data contribute to the accumulation of knowledge on the genetic diversity and prevalence of APMVs in wild bird populations. PMID- 26846091 TI - Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly. AB - BACKGROUND: Clinical and genetic heterogeneity in monogenetic disorders represents a major diagnostic challenge. Although the presence of particular clinical features may aid in identifying a specific cause in some cases, the majority of patients remain undiagnosed. Here, we investigated the utility of whole-exome sequencing as a diagnostic approach for establishing a molecular diagnosis in a highly heterogeneous group of patients with varied intellectual disability and microcephaly. METHODS: Whole-exome sequencing was performed in 38 patients, including three sib-pairs, in addition to or in parallel with genetic analyses that were performed during the diagnostic work-up of the study participants. RESULTS: In ten out of these 35 families (29 %), we found mutations in genes already known to be related to a disorder in which microcephaly is a main feature. Two unrelated patients had mutations in the ASPM gene. In seven other patients we found mutations in RAB3GAP1, RNASEH2B, KIF11, ERCC8, CASK, DYRK1A and BRCA2. In one of the sib-pairs, mutations were found in the RTTN gene. Mutations were present in seven out of our ten families with an established etiological diagnosis with recessive inheritance. CONCLUSIONS: We demonstrate that whole-exome sequencing is a powerful tool for the diagnostic evaluation of patients with highly heterogeneous neurodevelopmental disorders such as intellectual disability with microcephaly. Our results confirm that autosomal recessive disorders are highly prevalent among patients with microcephaly. PMID- 26846093 TI - Comparative transcriptome analysis of wheat embryo and endosperm responses to ABA and H2O2 stresses during seed germination. AB - BACKGROUND: Wheat embryo and endosperm play important roles in seed germination, seedling survival, and subsequent vegetative growth. ABA can positively regulate dormancy induction and negatively regulates seed germination at low concentrations, while low H2O2 concentrations promote seed germination of cereal plants. In this report, we performed the first integrative transcriptome analysis of wheat embryo and endosperm responses to ABA and H2O2 stresses. RESULTS: We used the GeneChip(r) Wheat Genome Array to conduct a comparative transcriptome microarray analysis of the embryo and endosperm of elite Chinese bread wheat cultivar Zhengmai 9023 in response to ABA and H2O2 treatments during seed germination. Transcriptome profiling showed that after H2O2 and ABA treatments, the 64 differentially expressed genes in the embryo were closely related to DNA synthesis, CHO metabolism, hormone metabolism, and protein degradation, while 121 in the endosperm were involved mainly in storage reserves, transport, biotic and abiotic stresses, hormone metabolism, cell wall metabolism, signaling, and development. Scatter plot analysis showed that ABA treatment increased the similarity of regulated patterns between the two tissues, whereas H2O2 treatment decreased the global expression similarity. MapMan analysis provided a global view of changes in several important metabolism pathways (e.g., energy reserves mobilization, cell wall metabolism, and photosynthesis), as well as related functional groups (e.g., cellular processes, hormones, and signaling and transport) in the embryo and endosperm following exposure of seeds to ABA and H2O2 treatments during germination. Quantitative RT-PCR analysis was used to validate the expression patterns of nine differentially expressed genes. CONCLUSIONS: Wheat seed germination involves regulation of a large number of genes involved in many functional groups. ABA/H2O2 can repress/promote seed germination by coordinately regulating related gene expression. Our results provide novel insights into the transcriptional regulation mechanisms of embryo and endosperm in response to ABA and H2O2 treatments during seed germination. PMID- 26846094 TI - Investigation of blood flow in the external carotid artery and its branches with a new 0D peripheral model. AB - BACKGROUND: Patient-specific modelling in clinical studies requires a realistic simulation to be performed within a reasonable computational time. The aim of this study was to develop simple but realistic outflow boundary conditions for patient-specific blood flow simulation which can be used to clarify the distribution of the anticancer agent in intra-arterial chemotherapy for oral cancer. METHODS: In this study, the boundary conditions are expressed as a zero dimension (0D) resistance model of the peripheral vessel network based on the fractal characteristics of branching arteries combined with knowledge of the circulatory system and the energy minimization principle. This resistance model was applied to four patient-specific blood flow simulations at the region where the common carotid artery bifurcates into the internal and external carotid arteries. RESULTS: Results of these simulations with the proposed boundary conditions were compared with the results of ultrasound measurements for the same patients. The pressure was found to be within the physiological range. The difference in velocity in the superficial temporal artery results in an error of 5.21 +/- 0.78 % between the numerical results and the measurement data. CONCLUSIONS: The proposed outflow boundary conditions, therefore, constitute a simple resistance-based model and can be used for performing accurate simulations with commercial fluid dynamics software. PMID- 26846095 TI - Bilateral orbital myeloid sarcoma preceding acute myeloid leukemia in an adult: a case report and review of the literature. AB - BACKGROUND: Acute myeloid leukemia is typically a disease of the older population and presents mostly in the fifth decade of life. Myeloid sarcoma is a rare initial presentation of acute myeloid leukemia. Previously it has only been documented in children and younger patients. CASE PRESENTATION: We present an unusual case of retro-orbital myeloid sarcoma as an initial presentation of acute myeloid leukemia in a 43-year-old Caucasian man, with rearrangement of chromosome 11q23 involving the MLL gene. CONCLUSIONS: We present an unusual case of retro orbital myeloid sarcoma as an initial presentation of acute myeloid leukemia in a 43-year-old man, with rearrangement of chromosome 11q23 involving the MLL gene. PMID- 26846096 TI - Homozygosity mapping identified a novel protein truncating mutation (p.Ser100Leufs*24) of the BBS9 gene in a consanguineous Pakistani family with Bardet Biedl syndrome. AB - BACKGROUND: Bardet Biedl Syndrome (BBS) is a rare condition of multi-organ dysfunction with characteristic clinical features of retinal degeneration, truncal obesity, postaxial polydactyly, genital anomaly, intellectual disability and renal dysfunction. It is a hetero-genetic disorder and nineteen BBS genes have been discovered so far. METHODS: Whole genome SNP genotyping was performed by using CytoScan(r) 750 K array (Affymetrix). Subsequently, the segregation of the disease locus in the whole family was carried out by genotyping STS markers within the homozygous interval. Finally, the mutation analysis was performed by Sanger DNA sequencing. RESULTS: In the present molecular study a consanguineous Pakistani family, with autosomal recessive BBS, was analyzed. The clinical analysis of affected individuals presented with synpolydactyly, obesity, intellectual disability, renal abnormality and retinitis pigmentosa. The presented phenotype was consistent with the major features of BBS syndrome. Homozygosity mapping identified a common homozygous interval within the known BBS9 locus. Sequence analysis of BBS9/PTHB1 gene revealed a single base deletion of c.299delC (p.Ser100Leufs*24) in exon 4. This frame-shift mutation presumably leads to a 122 amino acid truncated protein with complete loss of its C-terminal PTHB1 domain in combination with a partial loss of the N-terminal PTHB1 domain as well. BBS9/PTHB1 gene mutations have been shown to be associated with BBS syndrome and to the best of our knowledge this study reports the first Pakistani family linked to the BBS9 gene. CONCLUSION: Our molecular findings expand the mutational spectrum of BBS9 gene and also explain the genetic heterogeneity of Pakistan families with BBS syndrome. The growing number of mutations in BBS genes in combination with a detailed phenotypical description of patients will be helpful for genotype-phenotype correlation, targeted genetic diagnosis, prenatal screening and carrier testing of familial and non-familial BBS patients. PMID- 26846097 TI - Overexpression of the non-coding SOX2OT variants 4 and 7 in lung tumors suggests an oncogenic role in lung cancer. AB - Despite the advances in cancer therapy, lung cancer still remains the most leading cause of cancer death worldwide. The long non-coding RNAs (lncRNAs) are recently introduced as novel regulators of human cancers. SOX2 overlapping transcript (SOX2OT) is a cancer-associated lncRNA gene that encodes different alternatively spliced transcripts. Here, we investigated the alterations in the preferential expression of different SOX2OTs in twenty non-small cell lung cancer (NSCLC) patients by real-time quantitative reverse transcription PCR (qRT-PCR) method. We observed preferential expression of SOX2OT4 and SOX2OT7 in lung tumor tissues. The quantitative gene expression analysis revealed that >30 % of NSCLC tumors express SOX2OT4 (mean = 7.6 times) and SOX2OT7 (mean = 5.9 times) more than normal tissues, with higher expression in squamous cell carcinoma. Further, we observed overexpression of pluripotency-associated transcription factor, SOX2 in 47 % of our samples concordant with SOX2OT (R = 0.62, P value <0.05). Overexpression of OCT4A gene was also observed in 36.8 % of tumor tissues. Then, we investigated the effects of SOX2OT suppression in lung adenocarcinoma cell line, by means of RNAi. Cell characteristics of colony formation, apoptosis, 2-D mobility, and cell cycle progression were measured in control and treated A549 cells. The SOX2OT knockdown significantly reduced the colony formation ability of cancer cells; however, no alterations in the rate of apoptosis were detected. On the other hand, SOX2OT-suppressed cells had elevated accumulation in G2/M phase of cell cycle and exhibited limited mobility. Altogether, our findings support a potential oncogenic role for SOX2OT in non-small cell lung cancer tumor genesis and SOX2OT seems a promising therapeutic candidate for NSCLC. PMID- 26846098 TI - Clinical characteristics and prognostic indicators for metastatic melanoma: data from 446 patients in north China. AB - Melanoma is an extremely rare tumor in Asia. This retrospective study aimed to identify the clinical characteristics and prognostic factors of metastatic melanoma patients at Tianjin Medical University Cancer Hospital over the last 30 years. Survival analysis was performed with Kaplan-Meier, log-rank test, and multivariate Cox regression method using SPSS 19.0 software. The 1-, 2-, and 5 year survival rates of metastatic melanoma patients were 52, 32, and 16 %, respectively. Median overall survival (OS) was 13.5 months, median progression free survival (PFS) 9.0 months, and median disease-free survival 20.3 months. Furthermore, patients with a single metastatic site achieved better OS and PFS than those with two or more metastatic lesions (OS 21.6 vs. 8.9 months, P < 0.001; PFS 11.3 vs. 7.1 months, P < 0.001). Survival times of patients with visceral metastases were the shortest (OS 8.5 months; PFS 7.5 months). Specifically, patients with primary mucosal lesions had a worse OS (9.7 months) and PFS (6.8 months) than those with acral (19.2 and 15.6 months, respectively) or non-acral primary lesions (11.8 and 11.1 months, respectively). The treatment of advanced melanoma was unitary, and prognoses of patients with metastatic melanoma in China were poor. Visceral metastasis, multiple metastatic sites, and primary mucosal lesions were significant predictors of survival of patients with metastatic melanoma. Those with primary mucosal lesions had significantly worse survivals than those with primary cutaneous lesions. More active involvement in clinical studies and more feedback on various treatment options are required. PMID- 26846099 TI - Prognostic significance of nuclear or cytoplasmic nucleolin expression in human non-small cell lung cancer and its relationship with DNA-PKcs. AB - This study investigated the expression of nucleolin in tissue samples in patients with non-small cell lung cancer (NSCLC). Nucleolin was studied to determine whether it has a prognostic value and if its levels correlate with various clinicopathologic parameters. The relationship between nucleolin and expression of DNA-PKcs was also evaluated. Immunohistochemistry was used for detecting the expression levels of nucleolin and DNA-PKcs in tissues from 225 stage IA to IIIB NSCLC patients who underwent lung surgery. Nucleolin was observed predominantly in the cytoplasm, and some levels were observed in the nucleus. Nucleolin expression was higher in NSCLC tissues than adjacent normal lung tissues. Among 225 NSCLC patients, 117 (52.0 %) had high expression of nucleolin. The expression of nucleolin was significantly associated with pathologic stage (P = 0.013) and T status (P = 0.043). Multivariate analysis revealed that nucleolin, cytoplasmic nucleolin, and nuclear nucleolin expression were independent prognostic factors for both overall survival (OS) (P < 0.001) and disease-free survival (DFS) (P < 0.001). A high level of nuclear nucleolin served as an independent prognostic factor for better survival, while a high level of cytoplasmic nucleolin was closely associated with worse prognosis in NSCLC patients. The expression of nucleolin and cytoplasmic nucleolin positively correlated with DNA-PKcs (P < 0.001). These data suggest that nucleolin could be an effective treatment target and prognostic factor for patients with NSCLC. PMID- 26846100 TI - Manganese-superoxide dismutase (Mn-SOD) overexpression is a common event in colorectal cancers with mitochondrial microsatellite instability. AB - Mitochondrial displacement loop (D-loop) is a hot spot for mitochondrial DNA (mtDNA) alterations that effects cellular reactive oxygen species (ROS) generation. Manganese-superoxide dismutase (Mn-SOD) is a major antioxidant enzyme that protects cells from ROS-mediated damage. In the present study, we investigated the relationship between sequence alterations of mitochondrial D loop and Mn-SOD expression in colorectal cancer (CRC). Genotyping of entire mitochondrial D-loop (1124 bp) was carried out on mtDNA of analogous tumor and normal tissues from 35 CRC patients of south Indian origin by PCR-sequencing analysis. Tumor-specific large-scale mtDNA deletions and Mn-SOD expression was analyzed by PCR and Western blot analysis, respectively. We identified 87 polymorphisms in the D-loop region of tumor and/or control tissues. Polymorphisms were predominantly located in hypervariable region I (67.9 %) than in II (32.1 %) of D-loop. Significantly increased mtDNA microsatellite instability (mtMSI) [310'C' insertion (P = 0.00001) and T16189C (P = 0.0007)] and elevated Mn-SOD expression was observed in tumor tissues compared with controls. Interestingly, mtMSI was significantly high in tumors with Mn-SOD overexpression. Tumor-specific large-scale mtDNA deletions were not observed in CRC tissues. In conclusion, mtMSI and Mn-SOD overexpression are a common event in CRC. The analysis of mtMSI and/or Mn-SOD expression might help to identify patients at high risk for disease outcome, thereby helping to refine therapeutic decisions in CRC. PMID- 26846101 TI - Silencing Bag-1 gene via magnetic gold nanoparticle-delivered siRNA plasmid for colorectal cancer therapy in vivo and in vitro. AB - Apoptosis disorder is generally regarded as an important mechanism of carcinogenesis. Inducement of tumor cell apoptosis can be an effectual way to treat cancer. Bcl-2-associated athanogene 1 (Bag-1) is a positive regulator of Bcl-2 which is an anti-apoptotic gene. Bag-1 is highly expressed in colorectal cancer, which plays a critical role in promoting metastasis, poor prognosis, especially in anti-apoptotic function, and is perhaps a valuable gene target for colorectal cancer therapy. Recently, we applied a novel non-viral gene carrier, magnetic gold nanoparticle, and mediated plasmid pGPH1/GFP/Neo-Bag-1-homo-825 silencing Bag-1 gene for treating colorectal cancer in vivo and in vitro. By mediating with magnetic gold nanoparticle, siRNA plasmid was successfully transfected into cell. In 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, magnetic gold nanoparticle had no significant cytotoxicity and by which delivered RNA plasmid inhibited cell viability significantly (P < 0.05). Downregulation of Bag-1 promoted cell apoptosis (~47.0 %) in vitro and significantly decreased tumor growth when the cells were injected into nude mice. Based on the studies in vivo, the relative expression of Bag-1 was 0.165 +/- 0.072 at mRNA level and ~60 % at protein level. In further study, C-myc and beta catenin, mainly molecules of Wnt/beta-catenin pathway, were decreased notably when Bag-1 were silenced in nanoparticle plasmid complex-transfected Balb c/nude tumor xenograft. In conclusion, Bag-1 is confirmed an anti-apoptosis gene that functioned in colorectal cancer, and the mechanism of Bag-1 gene causing colorectal cancer may be related to Wnt/beta-catenin signaling pathway abnormality and suggested that magnetic gold nanoparticle-delivered siRNA plasmid silencing Bag-1 is an effective gene therapy method for colorectal cancer. PMID- 26846102 TI - Hepatitis B virus X protein reduces the stability of Nrdp1 to up-regulate ErbB3 in hepatocellular carcinoma cells. AB - Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) is the most widespread type of liver cancer. However, the underlying mechanism of HCC tumorigenesis is very intricate and HBV-encoded X protein (HBx) has been reported to play a key role in this process. It has been reported that HBx up-regulates the transcription of ErbB3. However, it remains unclear whether HBx can regulate ErbB3 expression at post-translational modification level. In this study, we showed that HBx interacts with ubiquitin ligase Nrdp1 (neuregulin receptor degradation protein 1) and decreases its stability, which results in the up regulation of ErbB3 and promotion of HCC cells. Moreover, the expression of ErbB3 was almost undetectable in normal liver tissues but was relative abundant in HCC tissues, and the level of ErbB3 and Nrdp1 significantly showed a negative correlation in HCC tissues. Taken together, these findings suggest that HBx promotes the progression of HCC by decreasing the stability of Nrdp1, which results in up-regulation of ErbB3, suggesting that ErbB3 may be a target for HCC therapy. PMID- 26846103 TI - A novel derivative of tetrandrine (H1) induces endoplasmic reticulum stress mediated apoptosis and prosurvival autophagy in human non-small cell lung cancer cells. AB - H1, a bromized derivative of tetrandrine, has been reported to induce apoptosis in human cancer cells. But, the underlying mechanism of apoptosis triggered by H1 is unclear. In the present study, we found that H1 triggered death receptor 5 (DR5)-dependent apoptosis in non-small cell lung cancer (NSCLC) cells. Further study showed that H1 activated ER stress through enforcing the expression of Bip/GRP78, IRE1alpha, p-eIF2alpha, and CHOP. Moreover, abrogating CHOP expression blocked DR5 upregulation and subsequent apoptosis, indicating that CHOP was essential for DR5-dependent apoptosis induced by H1. In addition, H1 greatly downregulated cellular FLICE-inhibitory protein (c-FLIP), and enhanced expression of c-FLIP protected cancer cells from apoptosis in spite of H1 therapy. Furthermore, we discovered that H1 induced autophagy in human NSCLC cells. Interestingly, the autophagy induced by H1 played a protective function in NSCLC cells and effectively weakened caspase-mediated apoptosis. In summary, these findings suggest that H1 induces DR5-dependent apoptosis in human NSCLC cells via stimulating ER stress signaling pathway, and pharmacologically inhibiting autophagy will be an efficient approach to synergize H1-caused apoptosis in lung cancer cells. PMID- 26846104 TI - DPYD gene polymorphisms are associated with risk and chemotherapy prognosis in pediatric patients with acute lymphoblastic leukemia. AB - We aimed to investigate the association between dihydropyrimidine dehydrogenase (DPYD) gene polymorphisms and the risk of pediatric acute lymphoblastic leukemia (ALL) and its prognosis after chemotherapy. A total of 147 pediatric ALL patients diagnosed by our hospital between January 2011 and December 2014 were included in the case group, and 102 healthy people who received a physical examination during the same time frame in our hospital were included in the control group. DNA sequencing was applied for site determination and genotyping of the DPYD 85T > C, 2194G > A, 1156G > T, and IVS14 + 1G > A polymorphisms. The genotype and allele frequencies of the two groups were compared. A significant difference was found in the comparison of the mutant gene and allele frequencies of the 85T > C polymorphism between the case and control groups (P < 0.05). The CT and CC genotypes in the 85T > C polymorphism were associated with the risk of the disease (OR = 1.592, 95 % CI = 1.010-2.509), suggesting that the recessive gene (85C) was more likely to lead to the occurrence of ALL compared with the dominant gene (85T) (P < 0.05). Patients carrying the C allele of the 85T > C polymorphism presented higher damage of their liver functions and higher infection rates compared with patients carrying the non-C allele (P < 0.05). A higher proportion of liver function damage and a higher infection rate were found in patients with the GA genotype in the IVS14 + 1G > A polymorphism compared with the GG genotype (P < 0.05). The complete remission (CR) rate in patients with the GG genotype in the IVS14 + 1G > A polymorphism was higher than in patients with the GA genotype (P = 0.020). After 5-fluorouracil/calcium folinate (5-FU/CF)-based chemotherapy, the event-free survival (EFS) rate of patients with the TT genotype was higher than patients with the CT and CC genotypes (P < 0.05). Our results revealed that the C allele of the 85T > C polymorphism might be associated with susceptibility to pediatric ALL. Patients carrying the C allele may have an increased risk of ALL. Thus, the 85T > C polymorphism may be a predictor of CR for pediatric ALL patients. PMID- 26846105 TI - The effects and mechanisms of SLC34A2 on tumorigenicity in human non-small cell lung cancer stem cells. AB - A novel paradigm in tumor biology suggests that non-small cell lung cancer (NSCLC) growth is driven by lung cancer stem cell-like cells (LCSCs), but molecular mechanisms regulating tumorigenic and self-renewal potential of LCSCs are still unclear. Here, we aim to investigate biological function of SLC34A2 in regulating tumorigenicity of LCSCs and its underlying mechanisms. Our findings testified that CD166(+) cells which were derived from fresh primary NSCLC samples displayed stem cell-like features. Fluorescence-activated cell sorting (FACS) analysis showed the presence of a variable fraction of CD166 cells in 15 out of 15 NSCLC samples. Significantly, CD166(+) LCSCs from primary NSCLC tumors expressed high level of SLC34A2 which was required for CD166(+) LCSCs tumorigenic and self-renewal potential. In NSCLC patient cohort, increased SLC34A2 expression correlated with histology, which suggests a potential role of SLC34A2 in CD166(+) LCSCs. Furthermore, Wnt/beta-catenin pathway and Bmi1 were found necessary for tumorigenicity and self-renewal capacity of CD166(+) LCSCs by a series in vitro and in vivo experiments. Then, our study indicated that SLC34A2 regulated Bmi1 to promote tumorigenic and self-renewal potential of CD166(+) LCSCs through Wnt/beta catenin pathway. In this study, the characterization of molecular basis of SLC34A2 in CD166(+) LCSCs not only allows for better understanding of the mechanisms regulating tumorigenicity of this specific population of NSCLC cells but also provides insight into the gradual improvement of more effective cancer therapies against this disease. PMID- 26846107 TI - The clinical and prognostic significance of CD14(+)HLA-DR(-/low) myeloid-derived suppressor cells in hepatocellular carcinoma patients receiving radiotherapy. AB - Myeloid-derived suppressor cells (MDSCs) are key player in mediating systemic immunosuppression, and their accumulation and expansion in the periphery and tumor have been iteratively observed in patients with various types of cancer. It has been reported that CD14(+)HLA-DR(-/low) MDSCs are increased in hepatocellular carcinoma (HCC) patients; however, the clinical significance of MDSC alteration in HCC patients after treatment is poorly studied. In this study, we examined the frequency of MDSCs in 92 HCC patients, 14 chronic liver disease patients without HCC, and 22 healthy controls by flow cytometric analysis. The associations between the clinical features and the frequency of MDSCs were analyzed. In particular, we further examined the prognostic impact of MDSCs on the overall survival of HCC patients receiving radiation therapy. The frequency of MDSCs in HCC patients was significantly increased and correlated with tumor stage, size, burden, and Child-Pugh classification but not with biochemical parameters of liver function. In HCC patients who received radiation therapy, the frequency of MDSCs after treatment significantly decreased and was inversely correlated with overall survival time. In multivariate analysis, only post-treatment MDSC ratio and Child-Pugh classification were correlated with the prognosis of HCC patients. Patients with a high frequency of MDSCs after radiotherapy should be closely followed, and the inhibition of MDSCs may improve the prognosis of patients. PMID- 26846106 TI - Hyperthermotherapy enhances antitumor effect of 5-aminolevulinic acid-mediated sonodynamic therapy with activation of caspase-dependent apoptotic pathway in human glioma. AB - Sonodynamic therapy (SDT) has shown great potential as an approach for cancer treatment, and hyperthermotherapy (HT) is also a promising cancer therapy. Here, we investigate whether HT could improve the efficacy of SDT and to make a preliminary exploration on potential mechanism. Xenograft tumor was established in nude mice model, and SNB19 and U87MG glioma cell lines were utilized for in vitro experiment. Alamar blue assay was performed to assess cell viability. Optical microscope was used to characterize the morphology changes of the glioma cells induced by SDT and HT treatments. Apoptotic rate, mitochondrial membrane potential (MMP), and intracellular production of reactive oxygen species (ROS) were examined by flow cytometer. The cell apoptosis of tumor tissues were detected by TUNEL assay. Furthermore, the expression of apoptosis-related proteins was detected with Western blot in vitro and immunohistochemistry in vivo. SDT plus HT group could significantly reduce the cell viability with circular-cell morphological change, compared with SDT group, and cell viability was decreased depending on raise of 5-ALA concentration, ultrasound exposure time, and temperature. The results also indicate that HT increased a conspicuous apoptosis, ROS production, and a remarkable loss in MMP induced by 5-ALA-SDT in vitro. Meanwhile, our data also demonstrated that the combined treatment could significantly induce apoptosis and delay tumor growth in vivo. Furthermore, in both in vitro and in vivo experiments, SDT plus HT group expressed significantly higher protein levels of Bax and cleaved caspase-3, 8, and 9 compared to SDT, HT, and control groups and significantly lower protein level of bcl-2 than the other three groups, while the expression of these proteins was unchanged between HT and control groups. HT may provide an important promotion on 5-ALA-SDT and further propose that SDT in combination with HT is a new potential application for the treatment of human glioma. PMID- 26846108 TI - Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells. AB - The tumour protein D52 isoform 1 (PC-1), a member of the tumour protein D52 (TPD52) protein family, is androgen-regulated and prostate-specific expressed. Previous studies confirmed that PC-1 contributes to malignant progression in prostate cancer with an important role in castration-resistant stage. In the present work, we identified its impact in mechanisms leading to neuroendocrine (NE) transdifferentiation. We established for long-term PC-1 overexpression an inducible expression system derived from the prostate carcinoma cell line LNCaP. We observed that PC-1 overexpression itself initiates characteristics of neuroendocrine cells, but the effect was much more pronounced in the presence of the cytokine interleukin-6 (IL-6). Moreover, to our knowledge, this is the first report that treatment with IL-6 leads to a significant upregulation of PC-1 in LNCaP cells. Other TPD52 isoforms were not affected. Proceeding from this result, we conclude that PC-1 overexpression enhances the IL-6-mediated differentiation of LNCaP cells into a NE-like phenotype, noticeable by morphological changes and increased expression of typical NE markers, like chromogranin A, synaptophysin or beta-3 tubulin. Immunofluorescent staining of IL-6-treated PC-1-overexpressing LNCaP cells indicates a considerable PC-1 accumulation at the end of the long branched neuron-like cell processes, which are typically formed by NE cells. Additionally, the experimentally initiated NE transdifferentiation correlates with the androgen receptor status, which was upregulated additively. In summary, our data provide evidence for an involvement of PC-1 in NE transdifferentiation, frequently associated with castration resistance, which is a major therapeutic challenge in the treatment of advanced prostate cancer. PMID- 26846109 TI - Low expression of PIDD is associated with cell proliferation and apoptosis in hepatocellular carcinoma. AB - p53-induced death domain protein (PIDD) facilitates p53-dependent apoptosis through the interaction with components of the death receptor signaling pathways. However, the role of PIDD in hepatocellular carcinoma (HCC) development remains unknown. In this study, we investigated the expression pattern of PIDD in clinical HCC samples and adjacent non-cancerous tissues using immunohistochemistrical and Western blot analyses. The results showed that PIDD was lowly expressed in HCC tissues and HCC cell lines, compared with the adjacent non-tumorous tissues and LO2 normal hepatocytes. In addition, clinicopathological analysis showed that the expression of PIDD was closely related with multiple clinicopathological variables, such as American Joint Committee on Cancer (AJCC) stage, AFP, and poor prognosis of HCC. Univariate and multivariate survival analyses demonstrated that PIDD could serve as an independent prognostic factor to predict the survival of HCC patients. We used serum starvation-refeeding experiment to explore the involvement of PIDD in HCC cell cycle regulation. We found that PIDD was accumulated in growth-arrested HCC cells and was progressively decreased when cells entered into S phase. Moreover, flow cytometry and cell counting kit-8 (CCK-8) assays indicated that depleting the expression of PIDD could facilitate cell cycle progression and accelerate cell proliferation in HepG2 cells, while overexpression of PIDD could result in cell cycle arrest at G1 phase and hinder the cell proliferation in Hep3B cells. Finally, flow cytometry revealed that overexpression of PIDD slightly increased the apoptosis of HCC cells. Taken together, we concluded that PIDD may be a valuable prognostic marker and promising therapeutic target of HCC. PMID- 26846111 TI - Erratum to: Regional brain dysregulation of Ca2+-handling systems in ketamine induced rat model of experimental psychosis. PMID- 26846110 TI - Angiopoietins Modulate Survival, Migration, and the Components of the Ang-Tie2 Pathway of Chronic Lymphocytic Leukaemia (CLL) Cells In Vitro. AB - In actuality, chronic lymphocytic leukaemia (CLL) remains an incurable haematopoietic malignancy of high prevalence amongst elderly populations in the West. Malignant CLL cells characteristically accumulate in the peripheral blood, bone marrow, lymph nodes, and spleen of CLL patients. There is evidence that CLL cells express Ang2 and Tie1, two central components of the Ang-Tie2 pro angiogenic pathway. Central to blood vessel development and maintenance, at present it remains unclear how the Ang-Tie2 pathway modulates CLL pathophysiology. Here we evaluate the status of the Ang-Tie2 pathway in CLL cells and assess Ang1 levels in plasma/cell medium from CLL samples. To understand how angiopoietins in the microenvironment regulate the components of Ang-Tie2 pathway, survival, migration, and metabolic fitness of CLL cells, we exposed CLL cells to recombinant angiopoietins. CLL plasma and CLL cells in culture present significant lower levels of Ang1. CLL cells simultaneously express Ang1, Ang2, and Tie1 mRNA, but lack that of Tie2 and its regulator, VE-PTP. Exposure to Ang1 confers survival advantage in the long-term, whereas Ang2 and trebananib, an angiopoietin blocker, proved detrimental. Angiopoietins differentially modulate expression of Ang1, Ang2, and Tie1 transcripts. Ang2, but not Ang1, induces the concomitant and transient expression of Tie2 and VE-PTP mRNA. Both angiopoietins, particularly Ang2, increase CLL-Tie1 expression and Ang1 clearly induces chemotaxis and transendothelial-like migration of CLL cells. Besides, changes in caspase and ATP content corroborate the sensitivity of CLL cells to angiopoietin exposure. Altogether, this work shows that angiopoietins regulate the fate of CLL cells in a Tie2-independent manner and highlights the potential of the Ang-Tie2 pathway as a therapeutic target in CLL research. PMID- 26846112 TI - Sox2 contributes to tooth development via Wnt signaling. AB - The transcription factor Sox2 is a stem cell marker that dictates cell lineage. It has been shown to mark the epithelial stem cells of the continuously growing mouse incisors. Sox2 also interferes with Wnt signaling by binding to beta catenin, a central mediator of the Wnt pathway. We show that these functions of Sox2 are essential for mouse molar development. Sox2 has previously been shown to play a role in the formation of new teeth from the existing dental epithelium. To assess Sox2 function related to cell migration within a tooth, we monitored cell movement by using a DiI system and observed that DiI moves from molar 1 to molar 2 during tooth development. However, upon temporal knockdown of Sox2, DiI remains in the molar 1 region. This study also provides novel insights into the role of Sox2 and the important validation of Sox2 as a potent target in Wnt signaling during tooth development. Our data reveal that the degradation of Wnt signaling caused by the knockdown of Sox2 results in a lack of cell migration during tooth development. PMID- 26846113 TI - Anti-GAPDHS antibodies: a biomarker of immune infertility. AB - Numerous investigations have focused on the detection of antisperm antibodies, which have a naturally occurring impact on male and female fertility. In this study, spermatogenic glyceraldehyde-3-phosphate dehydrogenase (GAPDHS) was considered to be a candidate biomarker of immune infertility. The concentrations of anti-GAPDHS antibodies in the sera of sterile individuals and fertile couples were measured by enzyme-linked immunosorbent assay. Sera were collected from immune infertile (n = 175) and fertile (n = 237) individuals and were screened by tray agglutination tests (TAT). Infertile sera were further divided into two groups according to the serum titers obtained by TAT (titers <= 1:8, n = 58; titers > 1:8, n = 117). The concentrations of anti-GAPDHS antibodies were significantly higher in the immune infertile group than in the fertile group and were much higher with regard to the increased degrees of sperm agglutination (titers > 1:8). Surprisingly, we found statistically significantly higher concentrations of antibodies in the sera of infertile men than in those of infertile women, and a similar statistical result was obtained in the sera when primary infertility was compared with secondary infertility. Thus, anti-GAPDHS antibodies seem to be a sensitive parameter in immune infertile detection and might be one of the main factors causing immune infertility. This factor might be valuable as an indicator in the clinical diagnosis and monitoring treatment of infertility. PMID- 26846114 TI - This I Believe: Random Thoughts on the Practice of Gastroenterology. PMID- 26846115 TI - Ipilimumab-Induced Gastrointestinal Toxicities: A Management Algorithm. AB - Ipilimumab is a cytotoxic T-lymphocyte-associated antigen-4-blocking monoclonal antibody, which has shown a significant survival benefit in metastatic melanoma patients. Despite being a promising therapy for a disease with an otherwise rather dismal prognosis, it is associated with several immune-related adverse effects (IRAE) mainly targeted toward the digestive tract, skin, liver, and hypothalamic-pituitary axis. Ipilimumab-induced gastrointestinal toxicity (IGT) include diarrhea (~44 %), colitis (~18 %), bowel perforation (<1 %), and pancreatitis (<1.5 %). Early recognition of IRAE and treatment initiation are critical to decrease the risk of further complications. Management included steroids as initial therapy, followed by infliximab (anti-tumor necrosis factor alpha antibody) and/or surgical option for complications like bowel perforation. We present a series of three patients with metastatic melanoma, who received treatment with ipilimumab, and presented with varying gastrointestinal clinical manifestations and complications. Through this case series, our attempt is to make practicing gastroenterologists cognizant about the wide spectrum of gastrointestinal toxicity of this rather new clinical entity, as well as to discuss management algorithm for IGT. PMID- 26846116 TI - The Initial Management and Endoscopic Outcomes of Dyspepsia in a Low-Risk Patient Population. AB - BACKGROUND AND AIMS: Dyspepsia is frequently encountered by primary care providers (PCP) and gastroenterologists (GI). While esophagogastroduodenoscopy (EGD) may be useful, current guidelines suggest a proton pump inhibitor (PPI) trial and H. pylori (HP) test-and-treat before EGD for low-risk patients. This study aimed to evaluate pre-EGD management and endoscopic outcomes in this population. METHODS: This was a retrospective cohort study of low-risk dyspepsia patients (age <=55, no alarm features) undergoing EGD at an ambulatory endoscopy center from January 2011 to March 2012. Adherences to initial management guidelines (PPI trial and HP test-and-treat strategy before EGD) were compared between PCP and GI. Endoscopic and pathologic outcomes were assessed for all patients. Statistical analyses were performed using Chi-squared test (categorical variables) and Student's t test (continuous variables). This study received IRB approval (2011P001715). RESULTS: A total of 309 low-risk patients underwent EGD for dyspepsia. Only 202 (65.4 %) had HP testing, and 220 (71.2 %) were trialed on any dose/length PPI pre-EGD, with no differences between PCP and GI. PPI exposure was similar between groups for all dose/duration except for trials >=8 weeks of any dose (46.9 % GI vs 34.3 % PCP, p = 0.03) and high dose (32 % GI vs 18.7 % PCP, p = 0.01). Overall, only 178 (57.6 %) patients had both HP testing and any PPI exposure pre-EGD (56.6 % GI vs 59 % PCP, p = 0.73). Significant pathology was rare, with gastritis (46.6 %) and HP (17.2 %) being most common. No malignancy was found. CONCLUSIONS: A significant proportion of low-risk dyspepsia patients did not receive any PPI trial or HP testing before EGD. Within this population, significant finding on EGD was rare, supporting the current noninvasive initial management guidelines for dyspepsia. PMID- 26846117 TI - When Should Antiplatelet Agents Be Resumed After Successful Endoscopic Hemostasis in Patients with Peptic Ulcer Bleeding? AB - BACKGROUND: During treatment for peptic ulcer bleeding (PUB), it is imperative to determine the effect of antiplatelet agents on recurrent bleeding in order to balance risks and benefits. AIMS: We compared the rate of recurrent bleeding in antiplatelet users and non-users. METHODS: This retrospective study analyzed prospectively collected data from PUB patients treated by endoscopic modalities between August 2007 and December 2014. We evaluated and compared the rate of recurrent bleeding within 30 days in antiplatelet users and non-users; we also categorized antiplatelet users into continuation (<=3 days) and withdrawal (>3 days) groups. RESULTS: A total of 490 patients were enrolled in the study, 302 (61.6 %) and 188 (38.4 %) in the non-user and antiplatelet user groups, respectively. The recurrent bleeding rate among antiplatelet users (10.1 %) was significantly higher than that among non-users (5.0 %; p = 0.029). Among 188 antiplatelet users, 51 (27.1 %) and 137 (72.9 %) were assigned to the continuation and withdrawal groups, respectively. The rate of recurrent bleeding did not differ significantly between groups (11.7 vs. 5.9 %, p = 0.241). Multivariate analysis revealed chronic kidney disease as a risk factor [odds ratio (OR) 2.890, 95 % confidence interval (CI) 1.079-7.742, p = 0.035]. However, antiplatelet use (OR 1.691, 95 % CI 0.813-3.517, p = 0.160) was not. CONCLUSIONS: This study highlights the need for clinicians to consider underlying diseases in antiplatelet users under the appropriate antiplatelet therapy during the post hemostasis period. Furthermore, the optimal time to resume antiplatelet agents may be 3 days after successful endoscopic hemostasis in patients with PUB. PMID- 26846118 TI - Impact of Colonoscopy Insertion Techniques on Adenoma Detection. AB - BACKGROUND: Low adenoma detection rate (ADR) predicts development of interval cancers, found mainly in the right (cecum-ascending) colon, where poor bowel preparation is an associated factor. Single-site studies reported increased detection of adenomas in the proximal colon segments by water exchange (WE). Data about colon cleansing revealed that WE had the greatest impact in the right colon. AIMS: To test the hypothesis that WE had the greatest impact on ADR in colon segments with the most favorable bowel cleanliness scores, namely the right colon. METHODS: We pooled right colon and overall ADR data of three similarly designed colonoscopy trials that compared WE, water immersion (WI) and insufflation of air or carbon dioxide (AICD) in a mixed gender European population. RESULTS: In this study, 1200 (704 males) subjects and were included. 288 were screening cases. Demographic and procedural data were comparable. Water exchange achieved significantly higher right colon <10 mm ADR (11.9 %, vs WI 6.9 %, p = 0.016; vs AICD 7.2 %, p = 0.025). Water exchange achieved the lowest proportions of poor bowel preparation and the highest right colon and overall Boston bowel preparation scale scores (p range 0.003, <0.0005). In patients with right colon excellent bowel cleanliness, water exchange was the only method significantly associated with right colon adenoma detection. One of the limitations is unblinded colonoscopists. CONCLUSIONS: In a mixed gender European population, water exchange is confirmed to be a superior insertion technique showing a significant increase in <10 mm right colon adenoma detection, achieving the cleanest colon and lowest proportions of poor bowel preparation requiring repeat procedures. CLINICALTRIALS. GOV NO: NCT01781650, 01954862, 01780818. PMID- 26846119 TI - GRG Profiles: John M. Carethers. PMID- 26846120 TI - Beneficial Effects of Fecal Microbiota Transplantation on Ulcerative Colitis in Mice. AB - BACKGROUND: Ulcerative colitis (UC) is a chronic condition and the most common form of inflammatory bowel disease. The goal of standard treatment is mainly to induce and maintain remission with anti-inflammatory, immunosuppressive agents, and/or colectomy. Fecal microbiota transplantation (FMT) has been used successfully to treat relapsing or refractory Clostridium difficile infection. The alteration of microbiota in mouse models of UC as well as in patients suggested the possibility of treating UC with FMT. AIMS: To study the effects of FMT on dextran sodium sulfate (DSS)-induced UC model in mice. METHODS: Littermates of BALB/c and C57BL/6J were randomized into four groups: normal control , treatment with DSS for 7 days (DSS - FMT), treatment with DSS followed by FMT for another 8 days (DSS + FMT), and treatment with DSS and FMT followed by another 5 days for recovery (remission). Body weight, survival rate, and DAI scores of mice in each group were recorded. Changes in distal colon were studied by histopathology. Alterations of spleen and lamina propria regulatory lymphocytes, major bacterial species in feces and inflammatory cytokines in colon were also studied. RESULTS: C57BL/6J mice experienced more significant weight loss than BALB/c mice after DSS treatment, regardless of whether the two strains of mice were co-housed or not. FMT caused reversal of DAI scores in BALB/c but not in C57BL/6J mice. In BALB/c mice, FMT also reduced colon inflammation that was paralleled by decreased inflammatory cytokine levels, altered bacterial microbiota, and regulatory lymphocyte proportions. CONCLUSIONS: FMT is effective in a mouse model of UC through its modulation on gut microbiota and the host immune system. PMID- 26846122 TI - Randomized trial of acupoints herbal patching in Sanfu Days for asthma in clinical remission stage. AB - BACKGROUND: Although China has a long history of using acupoints herbal patching (acupoints herbal patching means applying herbal patch on special acupoints to stimulate skin to form blisters, hyperemia, and even suppuration) in Sanfu Days (Sanfu Days are supposed to be the three hottest days in a year which is calculated by the ancient calendar) for the treatment of asthma, there is insufficient evidence to support its effectiveness and safety issues. This study investigated the efficacy and safety of acupoints herbal patching compared with placebo in participants with asthma in clinical remission stage. METHODS: We enrolled participants with asthma in clinical remission stage, above 13 years old and both genders in a randomized, double-blind and placebo-control trial at clinical center, School of Chinese Medicine, The University of Hong Kong to assess the effectiveness and safety of acupoints herbal patching, as compared with placebo, when added to guidelines-based therapy. The trial was conducted for three times (these three times were 19 July, 29 July and 8 August 2010), and the primary outcome was pulmonary function test. Secondary outcome was self-made questionnaire which were designed based on Traditional Chinese Medicine theory and clinical experience summary. RESULTS: Three hundred and twenty three eligible participants were enrolled, they were randomly assigned to acupoints herbal patching group (n = 165), placebo control group (n = 158). There was no significant difference in primary and secondary outcome as compared with placebo group at the end of 3rd treatment and four times follow ups. But sub-analysis of secondary outcome in four times follow ups showed that acupoints herbal patching significantly reduced the proportion of participants who didn't need medical treatment when they had a small rise in asthma-related symptoms increased from 6 15 % at 1st follow up and 0-7 % at 3rd follow up (P < 0.05). It indicated that the proportion of participants who can spontaneous resolution of an asthma attack increased through acupoints herbal patching. In addition, acupoints herbal patching was significantly superior to placebo in reducing the percentage of participants who were susceptibly waken up by asthma symptoms from 27-14 %, and the percentage of participants who had the symptom of running nose and sneezing before onset from 18-8 % at 2nd follow up (P < 0.05). Improvements also occurred with treatment group, it reduced the proportion of participants who were spontaneous sweating at 3rd follow up (P < 0.05). CONCLUSIONS: There was no significant difference between acupoints herbal patching and placebo in pulmonary function test in this study. Self-made questionnaire showed that the lasting effect of acupoints herbal patching was significantly better than placebo in reducing the need for medications to control asthma and the proportion of susceptible symptoms in participants with asthma in clinical remission stage. It showed that the low quality of life caused by asthma-related symptoms was significantly improved through acupoints herbal patching in Sanfu Days. Besides, acupoints herbal patching was as safe as placebo for chronic stable asthma. TRIAL REGISTRATION NUMBER: HKUCTR-1128, Registration date 22 Jul 2010. PMID- 26846121 TI - Insulinoma After Bariatric Surgery: Diagnostic Dilemma and Therapeutic Approaches. AB - Hypoglycemia is increasingly recognized as a complication of bariatric surgery. Typically, hypoglycemia does not appear immediately postoperatively, but rather more than 1 year later, and usually occurs 1-3 h after meals. While rare, insulinoma has been reported after bariatric surgery. Clinical factors which should raise suspicion for insulinoma and the need for comprehensive clinical and biochemical evaluation include hypoglycemia occurring in the fasting state, predating bariatric surgery, and/or worsening immediately postoperatively, and lack of response to conservative therapy. Localization and successful resection of insulinoma can be achieved using novel endoscopic ultrasound and surgical approaches. In summary, hypoglycemia presenting shortly after gastric bypass or with a dominant fasting pattern should be fully evaluated to exclude insulinoma. Additionally, evaluation prior to gastric bypass should include screening for history of hypoglycemia symptoms. PMID- 26846123 TI - Dual-Axis Rotational Angiography is Safe and Feasible to Detect Coronary Allograft Vasculopathy in Pediatric Heart Transplant Patients: A Single-Center Experience. AB - Coronary allograft vasculopathy (CAV) is the leading cause of graft failure in pediatric heart transplant recipients, also adding to mortality in this patient population. Coronary angiography is routinely performed to screen for CAV, with conventional single-plane or bi-plane angiography being utilized. Dual-axis rotational coronary angiography (RA) has been described, mostly in the adult population, and may offer reduction in radiation dose and contrast volume. Experience with this in the pediatric population is limited. This study describes a single-institution experience with RA for screening for CAV in pediatric patients. The catheterization database at our institution was used to identify pediatric heart transplant recipients having undergone RA to screen for CAV. Procedural data including radiation dose, fluoroscopy time, contrast volume, and procedure time were collected for each catheterization. The number of instances in which RA was not successful, ECG changes were present, and CAV was detected were also collected for each catheterization. A total of 97 patients underwent 345 catheterizations utilizing RA. Median radiation dose-area product per kilogram was found to be 341.7 (mGy cm(2)/kg), total air kerma was 126.8 (mGy), procedure time was 69 min, fluoroscopy time was 9.9 min, and contrast volume was 13 ml. A total of 17 (2 %) coronary artery injections out of 690 could not be successfully imaged using RA. A total of 14 patients had CAV noted at any point, 10 of whom had progressive CAV. Electrocardiographic changes were documented in a total of 10 (3 %) RA catheterizations. Procedural characteristics did not differ between serial catheterizations. RA is safe and feasible for CAV screening in pediatric heart transplant recipients while offering coronary imaging in multiple planes compared to conventional angiography. PMID- 26846124 TI - Combinations of Histone Modifications for Pattern Genes. AB - Histone post-translational modifications play important roles in transcriptional regulation. It is known that multiple histone modifications can act in a combinatorial manner. In this study, we investigated the effects of multiple histone modifications on expression levels of five gene categories (four kinds of pattern genes and non-pattern genes) in coding regions. The combinatorial patterns of modifications for the five gene categories were also studied in the regions. Our results indicated that the differences in the expression levels between any two gene categories were significant. There were some corresponding differences in multiple histone modification levels among the five gene categories. Multiple histone modifications jointly impacted expression levels of every gene category. Four mutual combinations of histone modifications were found and analyzed. PMID- 26846125 TI - Are pit latrines in urban areas of Sub-Saharan Africa performing? A review of usage, filling, insects and odour nuisances. AB - BACKGROUND: A pit latrine is the most basic form of improved sanitation which is currently used by a number of people around the globe. In spite of the wide spread use, known successes and advantages associated with pit latrines, they have received little attention in form of research and development. This review focuses on the usage and performance (filling, smell and insect nuisance) of pit latrines in urban areas of sub-Saharan Africa (SSA) and proposes approaches for their improvements and sustainability. METHODS: Current pit latrine usage within urban SSA was calculated from Joint Monitoring Programme (JMP) water and sanitation country-files. We conducted a literature search and review of documents on pit latrine usage, filling, smell and insect nuisances in urban areas of SSA. Findings of the review are presented and discussed in this paper. RESULTS AND DISCUSSION: Pit latrines are in use by more than half the urban population in SSA and especially among low income earners. An additional 36 million people in urban areas of SSA have adopted the pit latrine since 2007. However, their performance is unsatisfactory. Available literature shows that contributions have been made to address shortfalls related to pit latrine use in terms of science and technological innovations. However, further research is still needed. CONCLUSION: Any technology and process management innovations to pit latrines should involve scientifically guided approaches. In addition, development, dissemination and enforcement of minimum pit latrine design standards are important while the importance of hygienic latrines should also be emphasized. PMID- 26846126 TI - Key successes and challenges in providing mental health care in an urban male remand prison: a qualitative study. AB - PURPOSE: This study aimed to describe the workings of an urban male remand prison mental health service exploring the key challenges and successes, levels of integration and collaboration with other services. METHOD: A purposive sampling was used to recruit key prison and healthcare professionals for in-depth interviews. A thematic analysis was used to analyse transcripts based on an initial coding frame of several predefined themes. Other key themes were also identified. RESULTS: Twenty-eight interviews were conducted. Prisoners referred to the service had complex, sometimes acute mental illness requiring specialist assessment and treatment. Key successes of the in-reach service included the introduction of an open referral system, locating a mental health nurse at reception to screen all new prisoners and a zoning system to prioritise urgent or non-urgent cases. Achieving an integrated system of healthcare was challenging because of the numerous internal and external services operating across the prison, a highly transient population, limited time and space to deliver services and difficulties with providing inpatient care (e.g., establishing the criteria for admission and managing patient flow). Collaborative working between prison and healthcare staff was required to enable best care for prisoners. CONCLUSIONS: The prison mental health in-reach service worked well in assessing and prioritising those who required specialist mental health care. Although the challenges of working within the prison context limited what the in-reach team could achieve. Further work was needed to improve the unit environment and how best to target and deliver inpatient care within the prison. PMID- 26846127 TI - Ethnicity and cardiovascular health inequalities in people with severe mental illnesses: protocol for the E-CHASM study. AB - PURPOSE: People with severe mental illnesses (SMI) experience a 17- to 20-year reduction in life expectancy. One-third of deaths are due to cardiovascular disease. This study will establish the relationship of SMI with cardiovascular disease in ethnic minority groups (Indian, Pakistani, Bangladeshi, black Caribbean, black African and Irish), in the UK. METHODS: E-CHASM is a mixed methods study utilising data from 1.25 million electronic patient records. Secondary analysis of routine patient records will establish if differences in cause-specific mortality, cardiovascular disease prevalence and disparities in accessing healthcare for ethnic minority people living with SMI exist. A nested qualitative study will be used to assess barriers to accessing healthcare, both from the perspectives of service users and providers. RESULTS: In primary care, 993,116 individuals, aged 18+, provided data from 186/189 (98 %) practices in four inner-city boroughs (local government areas) in London. Prevalence of SMI according to primary care records, ranged from 1.3-1.7 %, across boroughs. The primary care sample included Bangladeshi [n = 94,643 (10 %)], Indian [n = 6086 (6 %)], Pakistani [n = 35,596 (4 %)], black Caribbean [n = 45,013 (5 %)], black African [n = 75,454 (8 %)] and Irish people [n = 13,745 (1 %)]. In the secondary care database, 12,432 individuals with SMI over 2007-2013 contributed information; prevalent diagnoses were schizophrenia [n = 6805 (55 %)], schizoaffective disorders [n = 1438 (12 %)] and bipolar affective disorder [n = 4112 (33 %)]. Largest ethnic minority groups in this sample were black Caribbean [1432 (12 %)] and black African (1393 (11 %)). CONCLUSIONS: There is a dearth of research examining cardiovascular disease in minority ethnic groups with severe mental illnesses. The E-CHASM study will address this knowledge gap. PMID- 26846128 TI - Synthesis and Evaluation of a Zr-89-Labeled Monoclonal Antibody for Immuno-PET Imaging of Amyloid-beta Deposition in the Brain. AB - PURPOSE: The aim of this study was to evaluate the in vitro and in vivo characteristics of [(89)Zr]JRF/AbetaN/25, a radiolabeled monoclonal antibody directed against amyloid-beta (Abeta). PROCEDURES: JRF/AbetaN/25 was labeled with (89)Zr following modification with desferal. The affinity of the tracer for Abeta1-40 was determined in a saturation binding assay. In vitro stability was evaluated, and in vivo plasma stability and biodistribution of [(89)Zr]Df-Bz JRF/AbetaN/25 were determined in wild-type mice. To evaluate whether the antibody can cross the blood-brain barrier, brain uptake in wild-type mice was additionally assessed by ex vivo autoradiography. RESULTS: [(89)Zr]Df-Bz JRF/AbetaN/25 was obtained in an average radiochemical yield of 50 % and a radiochemical purity of >97 %. A saturation binding assay demonstrated specific binding of [(89)Zr]Df-Bz-JRF/AbetaN/25 to Abeta1-40 with nanomolar affinity. The tracer was stable in buffer and proved to be stable in vivo with >92 % intact monoclonal antibody (mAb) remaining in the plasma at 48 h post injection. A biodistribution study showed a slow blood clearance with no significant accumulation of activity in any of the organs. Furthermore, [(89)Zr]Df-Bz JRF/AbetaN/25 demonstrated modest brain penetration, which slowly decreased in time. This cerebral uptake was confirmed by ex vivo autoradiography. CONCLUSIONS: [(89)Zr]Df-Bz-JRF/AbetaN/25 binds with high affinity to Abeta1-40. The tracer displays an acceptable in vivo stability and is able to cross the blood-brain barrier. [(89)Zr]Df-Bz-JRF/AbetaN/25 might therefore be a potential candidate for in vivo imaging of Abeta deposition in the brain. PMID- 26846130 TI - Multilevel Resistance Switching Memory in La2/3Ba1/3MnO3/0.7Pb(Mg1/3Nb2/3)O3 0.3PbTiO3 (011) Heterostructure by Combined Straintronics-Spintronics. AB - We demonstrate a memory device with multifield switchable multilevel states at room temperature based on the integration of straintronics and spintronics in a La2/3Ba1/3MnO3/0.7Pb(Mg1/3Nb2/3)O3-0.3PbTiO3 (PMN-PT) (011) heterostructure. By precisely controlling the electric field applied on the PMN-PT substrate, multiple nonvolatile resistance states can be generated in La2/3Ba1/3MnO3 films, which can be ascribed to the strain-modulated metal-insulator transition and phase separation of Manganite. Furthermore, because of the strong coupling between spin and charge degrees of freedom, the resistance of the La2/3Ba1/3MnO3 film can be readily modulated by magnetic field over a broad temperature range. Therefore, by combining electroresistance and magnetoresistance effects, multilevel resistance states with excellent retention and endurance properties can be achieved at room temperature with the coactions of electric and magnetic fields. The incorporation of ferroelastic strain and magnetic and resistive properties in memory cells suggests a promising approach for multistate, high density, and low-power consumption electronic memory devices. PMID- 26846129 TI - Bioluminescence Imaging of Colonization and Clearance Dynamics of Brucella Suis Vaccine Strain S2 in Mice and Guinea Pigs. AB - PURPOSE: The goal of this study was to develop a plasmid-based lux bio-reporter for use to obtain in vivo images of Brucella suis vaccine strain 2 (B.suis S2) infection with high resolution and good definition. PROCEDURES: The pBBR-lux (pBBR1MCS-2-lxCDABE) plasmid that carries the luxCDABE operon was introduced into B. suis S2 by electroporation yielding B. suis S2-lux. The spatial and temporal transit of B. suis S2 in mice and guinea pigs was monitored by bioluminescence imaging. RESULTS: The plasmid pBBR-lux is stable in vivo and does not appear to impact the virulence or growth of bacteria. This sensitive luciferase reporter could represent B. suis S2 survival in real time. B. suis S2 mainly colonized the lungs, liver, spleen, and uterus in mice and guinea pigs as demonstrated by bioluminescence imaging. CONCLUSION: The plasmid-based lux bioreporter strategy can be used to obtain high resolution in vivo images of B. suis S2 infection in mice and guinea pigs. PMID- 26846131 TI - Survey of ankle-brachial pressure index use and its perceived barriers by general practitioners in the UK. AB - BACKGROUND: Peripheral arterial disease (PAD) is often undetected until complications arise, despite it being a major healthcare burden and an independent risk factor for cardiovascular death and systemic atherosclerosis. Appropriate diagnostic tools are as important as clinical knowledge and skill to investigate patients for PAD. Currently, the ankle-brachial pressure index (ABPI) is the recommended diagnostic tool for PAD. PURPOSE: We explore current opinions on ABPI by general practitioners (GPs) and the limitations to its implementation in primary care practice. METHODS: GPs attending a regional 1-day study event, were surveyed in October 2014. Survey questionnaires were placed at the top of each conference pack for each attendee. The survey questionnaire was modelled from the ankle-brachial index (ABI) usage survey questionnaire used in the PAD Awareness, Risk and Treatment: New Resources for Survival (PARTNERS) preceptorship study. RESULTS: All respondents were GPs, with a survey response rate of 77.1%. All respondents regarded ABPI as an important test, that is primarily performed by nursing staff (79.5%) in their respective GP surgeries. 70% and 97% of GPs found ABPI useful for the diagnosis of asymptomatic and symptomatic PAD, respectively. 69% of GPs regarded ABPI as a feasible test in primary care practice. Time constraints (84%), staff availability (89%) and staff training (72%) were cited as the main limitations to its use. CONCLUSIONS: Targeted training of nursing staff may improve ABPI usage, although a less time consuming test for PAD may be another option. PMID- 26846132 TI - Numerical determination of non-Langmuirian adsorption isotherms of ibuprofen enantiomers on Chiralcel OD column using ultraviolet-circular dichroism dual detector. AB - Competitive adsorption isotherm of ibuprofen enantiomers on Chiralcel OD stationary phase at 298K was determined by the application of inverse method. Transport dispersive (TD) chromatography model was used to describe mass balances of the enatiomers. Axial dispersion and mass transfer coefficients were estimated from a series of linear pulse experiments. It was found that the overloaded elution profile of total concentration of racemic ibuprofen cannot be satisfactorily fitted by substituting bi-Langmuir model, the most widely used isotherm model for enantiomers, into TD model and tuning the isotherm parameters. UV-CD dual detector setup was then applied to obtain the individual overloaded elution profiles of both enantiomers. The more informative experimental data revealed non-Langmuirian adsorption behavior of ibuprofen enantiomers on chiralcel OD stationary phase. Two analytical binary isotherm models, both accounting for adsorbate-adsorbate interactions and having the feature of inflection points, were then evaluated. A comparison between quadratic model and Moreau model showed that the former gives better fitting results. The six parameters involved in quadratic model were determined stepwisely. Three of them were first obtained by fitting overloaded elution profiles of S-ibuprofen. The other three were then acquired by fitting overloaded elution profiles of both enantiomers recorded by UV-CD dual detector for racemic ibuprofen. A further attempt was also made at reducing the number of quadratic model parameters. PMID- 26846134 TI - Spiritual wellbeing predicting depression: Is it relevant? PMID- 26846133 TI - Lifestyle modification and weight reduction among low-income patients with the metabolic syndrome: the CHARMS randomized controlled trial. AB - Although weight is an important intervention target among patients with metabolic syndrome, few trials have recruited low-income minority populations. The Community Health and Risk-reduction for Metabolic Syndrome randomized controlled trial aimed to examine the effects of a lifestyle intervention on weight and metabolic syndrome components among low-income minority adults. We randomized 120 adults with metabolic syndrome to standard medical care (N = 60) or a lifestyle intervention (N = 60). Using an intent-to-treat approach, we found significant intervention effects on weight [B = -0.452; SE = 0.122; 95 % confidence intervals (CI) -0.653 to -0.251) and glucose levels at 6-months (B = -0.522, SE = 0.234, 95 % CI -0.907 to -0.138). These changes were maintained through the 12-month assessment. No significant effects were observed on insulin resistance or other metabolic syndrome components. Our intervention was successful in achieving modest but significant weight loss and reduction in fasting glucose among low income minority subjects with metabolic syndrome. PMID- 26846135 TI - Improved safety of biologic therapy for rheumatoid arthritis over the 8-year period since implementation in Japan: long-term results from a multicenter observational cohort study. AB - This study aimed to compare the long-term safety of biologics by initiation year of treatment in patients with rheumatoid arthritis (RA) in Japan. RA patients who started their first biologics including infliximab, etanercept, adalimumab, and tocilizumab between 2003 and 2008 were identified in the Tsurumai Biologics Communication Registry (TBCR), multicenter observational cohort, and followed for 2 years or until discontinuation of the drugs. We identified baseline predictors for adverse events (AEs) resulting in discontinuation of the first TNFI using Cox proportional hazards regression analysis. A total of 874 cases (1,340 person years) were observed. During the observation period, 96 AEs (4.7 events/100 person-years) occurred. From 2003 to 2008, there were significant changes in disease duration, Steinbrocker stage, and disease activity in those aged <=64 years with no increase of incidence of AEs, whereas those aged >64 years had no significant changes in these variables. In the later initiation year of treatment with biologics, the fewer AEs were observed (log-rank, p = 0.017, 2008 vs. 2003 2005). Multivariate analysis showed that the initiation year significantly impacted the incidence of AEs 6 months into the observation period [initiation at 2008 (vs. 2003-2005): OR: 0.30, 95 % CI: (0.14-0.68)] after adjusting for variables at baseline. The decrease of AEs in the later initiation year was evident in those aged >64 years. The safety of biologic therapy improved over the course of the 8 years from its implementation in Japan. PMID- 26846136 TI - Anatomical and computed tomography study of the eighth costochondral junction: topography for costochondral graft harvesting. AB - INTRODUCTION: Costochondral grafts have long been used in maxillofacial reconstruction, but have been little used in trauma and orthopedic cases. This surgical technique requires that a graft be harvested from the thorax in the area of the eighth rib. Pleuropulmonary complications are very rare. Although the harvesting technique is simple, it needs to be demystified. GOAL OF STUDY: This study was performed to define anatomical relationships in the eighth costochondral junction and identify topographical and anatomical landmarks that will make it easier to harvest this structure. METHOD: This was a two-part study. First, an anatomical study was carried out on human cadaver thoraxes to define topographical landmarks and study the anatomical surroundings of the eighth costochondral junction. Second, an imaging study was performed using a database of existing patient computed tomography (CT) scans of the chest and abdomen to confirm the topographical landmarks defined in the first part of the study. The spine was used as a reference for both studies. The location of the eighth costochondral junction was defined relative to the spinal processes along with its location on the lower rib cage hemiperimeter in the transverse plane starting at the corresponding spinous process. RESULTS: The eighth costochondral junction was in line with the spinal process of the twelfth thoracic vertebra in the vast majority of cases and located at two-thirds of the lower rib cage hemiperimeter from the posterior median sulcus, regardless of the patient's chest shape, age and gender. This junction was always located under a single muscle (external oblique) and protected by a thick perichondrium layer, which separates it from the intercostal pedicles, endothoracic fascia and parietal pleura. DISCUSSION: This two-part study has identified reliable landmarks for harvesting of an osteochondral graft at the eighth costochondral junction and, by describing its anatomical surroundings, helps take the mystery out of its harvesting. These landmarks were identified in supine cadavers and in free-breathing patients lying in supine for the CT portion. This position must be used when identifying these landmarks in a patient undergoing costochondral autograft harvesting for cartilage reconstruction. PMID- 26846137 TI - The styloauricular muscle: clinical relevance and literature review of this rare muscle. AB - PURPOSE: In humans, the styloauricularis is a rare muscle extending from the tragal cartilage of the auricle to the styloid process. When it contracts, by bearing on the styloid process, it increases the cephalo-auricular angle. It can be a landmark for the facial nerve. We report a case with bilateral presence of the styloauricularis. METHODS: Bilateral presence of the styloauricularis was discovered during routine dissection of the head and neck. RESULTS: In the presented case, styloauricularis muscles arose from the cartilage of the external acoustic meatus on both sides of the head, crossing halfway along the facial nerve trunk and inserting the styloid process. Both muscles were vascularized by a branch of the posterior auricular artery, and innervated by the facial nerve. CONCLUSIONS: The ventral auricular muscle, formed by the auricular parotid and the styloauricular muscles, is a muscle that lowers and abducts the auricle in animals. There is generally considered to be no equivalent for these muscles in humans, however, this bilateral case reveals evidence to the contrary. There is a dearth of scientific literature about the styloauricularis. The study of this muscle demonstrated the usefulness of comparative anatomy in understanding its action in increasing the cephalo-auricular angle. PMID- 26846138 TI - Associations of dietary diversity scores and micronutrient status in adolescent Mozambican girls. AB - PURPOSE: In low-income settings, dietary diversity scores (DDSs) often predict the micronutrient adequacy of diets, but little is known about whether they predict levels of biochemical indicators of micronutrient status. METHODS: In 2010, we studied two samples of non-pregnant 14- to 19-year-old girls in central Mozambique, the first in January-February ('hunger season'; n = 227) and the second in May-June (harvest season; n = 223). In this paper, we examined whether a low Women's Dietary Diversity Score (WDDS) predicts a low concentration of haemoglobin, serum ferritin, zinc, and folate, and plasma retinol in adolescent Mozambican girls. We constructed three scores: WDDS based on 24-h recalls, WDDS15g based on 24-h recall and employing a 15 g limit, and 7dWDDS based on 7 day food frequency questionnaires. Logistic regression models, stratified by season, were used to estimate the odds of having a low concentration of a status indicator (<=25th percentile of the season-specific distribution or cut-off from the literature) in those with a low score compared to those with a higher score. RESULTS: In January-February, after adjusting for confounders, a low (<=3) WDDS and a low (<=5) 7dWDDS were each associated with higher odds of having low serum zinc compared to having a higher score, regardless of which of the two types of cut-offs for serum zinc was used. These associations were not present in May June. CONCLUSIONS: Our data from Mozambique suggest that dietary diversity is associated with serum zinc, but this association seems to be limited to the hunger season. PMID- 26846139 TI - Reperfusion in non-occlusive mesenteric ischaemia (NOMI): effectiveness of CT in an emergency setting. AB - OBJECTIVE: To investigate the CT features of reperfusion (presence/absence) in non-occlusive mesenteric ischaemia (NOMI) and their prognostic value in an emergency setting. METHODS: A revision was undertaken of imaging from 20 patients (16 males/4 females) with a dismissal summary of NOMI. All patients had previously undergone a minimum of one multidetector CT examination, and consequently underwent surgery (n = 8), autopsy (n = 2), angiography (n = 1) or endoscopy (n = 9). An evaluation of the CT scans was conducted to determine vessels, mesentery, bowel and peritoneal cavity features. The superior mesenteric artery (SMA) average diameter of NOMI cases were compared with 30 controlled cases. Kappa, Kolmogorov-Smirnov (K-S) and Fisher's exact tests were used for statistical analysis. RESULTS: A mean SMA diameter significantly smaller than that of the controlled cases was found for patients with NOMI (K-S test: D = 0.75, p = 3.7 * 10-08). Fisher's exact tests showed a strong connection between the presence of reperfusion and mesenteric fat stranding (p = 0.026), bowel wall thickening (p = 3.2 * 10-05) and a high attenuation of the bowel wall on unenhanced CT images (p = 2.8 * 10-04). A reduction in mortality was significantly linked to the combination of normal mesenteric vessels and wall thickening (p = 0.034). CONCLUSION: Analysis of not only vessels findings but also mesentery and bowel CT features will support the identification of NOMI with or without a reperfusion event in an emergency setting. A strong correlation between some CT features and lower mortality exists. ADVANCES IN KNOWLEDGE: CT features of NOMI with or without reperfusion are demonstrated. Correctly assessing the presence of reperfusion in NOMI, may allow better management of these conditions in the emergency setting. PMID- 26846141 TI - Induction of S-Phase Arrest in Human Glioma Cells by Selenocysteine, a Natural Selenium-Containing Agent Via Triggering Reactive Oxygen Species-Mediated DNA Damage and Modulating MAPKs and AKT Pathways. AB - Selenocysteine (SeC) a natural available selenoamino acid exhibits novel anticancer activities against human cancer cell lines. However, the growth inhibitory effect and mechanism of SeC in human glioma cells remain unclear. The present study reveals that SeC time- and dose-dependently inhibited U251 and U87 human glioma cells growth by induction of S-phase cell cycle arrest, followed by the marked decrease of cyclin A. SeC-induced S-phase arrest was achieved by inducing DNA damage through triggering generation of reactive oxygen species (ROS) and superoxide anion, with concomitant increase of TUNEL-positive cells and induction of p21waf1/Cip1 and p53. SeC treatment also caused the activation of p38MAPK, JNK and ERK, and inactivation of AKT. Four inhibitors of MAPKs and AKT pathways further confirmed their roles in SeC-induced S-phase arrest in human glioma cells. Our findings advance the understanding on the molecular mechanisms of SeC in human glioma management. PMID- 26846140 TI - The Effects of Ellagic Acid upon Brain Cells: A Mechanistic View and Future Directions. AB - Ellagic acid (EA, 2,3,7,8-tetrahydroxy-chromeno; C14H6O8) is a polyphenol derived from fruits (pomegranates, berries) and nuts. EA exhibits antioxidant capacity and induces anti-inflammatory actions in several mammalian tissues. EA has been characterized as a possible neuroprotective agent, but the number of reports is still limited to conclude whether and how EA exerts neuroprotection in humans. In this regard, performing additional studies considering the potential beneficial and/or toxicological roles for EA on brain cells would be an important step towards fully understanding of when and how EA may be securely utilized by humans as a neuroprotective agent. The aim of the present work is to discuss data related to the neuronal and glial effects of EA and the mechanisms underlying such events. Moreover, future directions are suggested as a potential guide to be utilized by researchers interested in investigating the neuronal and glial actions of EA hereafter. PMID- 26846142 TI - Intranasal Delivery of Recombinant NT4-NAP/AAV Exerts Potential Antidepressant Effect. AB - The present study was designed to construct a recombinant adeno-associated virus (rAAV) which can express NAP in the brain and examine whether this virus can produce antidepressant effects on C57 BL/6 mice that had been subjected to open field test and forced swimming test, via nose-to-brain pathway. When the recombinant plasmid pGEM-T Easy/NT4-NAP was digested by EcoRI, 297 bp fragments can be obtained and NT4-NAP sequence was consistent with the designed sequence confirmed by DNA sequencing. When the recombinant plasmid pSSCMV/NT4-NAP was digested by EcoRI, 297 bp fragments is visible. Immunohistochemical staining of fibroblasts revealed that expression of NAP was detected in NT4-NAP/AAV group. Intranasal delivery of NT4-NAP/AAV significantly reduced immobility time when the FST was performed after 1 day from the last administration. The effects observed in the FST could not be attributed to non-specific increases in activity since intranasal delivery of NT4-NAP/AAV did not alter the behavior of the mice during the open field test. The results indicated that a recombinant AAV vector which could express NAP in cells was successfully constructed and NAP may be a potential target for therapeutic action of antidepressant treatment. PMID- 26846143 TI - Applying Dataflow Architecture and Visualization Tools to In Vitro Pharmacology Data Automation. AB - The pace and complexity of modern drug discovery places ever-increasing demands on scientists for data analysis and interpretation. Data flow programming and modern visualization tools address these demands directly. Three different requirements-one for allosteric modulator analysis, one for a specialized clotting analysis, and one for enzyme global progress curve analysis-are reviewed, and their execution in a combined data flow/visualization environment is outlined. PMID- 26846145 TI - The impact of an educational pain management booklet intervention on postoperative pain control after cardiac surgery. AB - BACKGROUND: Relevant discharge information about the use of analgesic medication and other strategies may help patients to manage their pain more effectively and prevent postoperative persistent pain. AIMS: To examine patients' pain characteristics, analgesic intake and the impact of an educational pain management booklet intervention on postoperative pain control after cardiac surgery. Concerns about pain and pain medication prior to surgery will also be described. METHODS: From March 2012 to September 2013, 416 participants (23% women) were consecutively enrolled in a randomized controlled trial. The intervention group received usual care plus an educational booklet at discharge with supportive telephone follow-up on postoperative day 10, and the control group received only usual care. The primary outcome was worst pain intensity (The Brief Pain Inventory - Short Form). Data about pain characteristics and analgesic use were collected at 2 weeks and at 1, 3, 6 and 12 months post-surgery. General linear mixed models were used to determine between-group differences over time. RESULTS: Twenty-nine percent of participants reported surgically related pain at rest and 9% reported moderate to severe pain at 12 months post-surgery. Many participants had concerns about pain and pain medication, and analgesic intake was insufficient post-discharge. No statistically significant differences between the groups were observed in terms of the outcome measures following surgery. CONCLUSION: Postoperative pain and inadequate analgesic use were problems for many participants regardless of group allocation, and the current intervention did not reduce worst pain intensity compared with control. Further examination of supportive follow-up monitoring and/or self-management strategies post-discharge is required. PMID- 26846146 TI - Achieving universal testing for malaria. PMID- 26846147 TI - Distribution of Petrosavia sakuraii (Petrosaviaceae), a rare mycoheterotrophic plant, may be determined by the abundance of its mycobionts. AB - Petrosavia sakuraii (Petrosaviaceae) is a rare, mycoheterotrophic plant species that has a specific symbiotic interaction with a narrow clade of arbuscular mycorrhizal (AM) fungi. In the present study, we tested the hypothesis that the distribution and abundance of mycobionts in two P. sakuraii habitats, Nagiso and Sengenyama (central Honshu, Japan), determine the distribution pattern of this rare plant. Nagiso is a thriving habitat with hundreds of P. sakuraii individuals per 100 m(2), whereas Sengenyama is a sparsely populated habitat with fewer than 10 individuals per 100 m(2). AM fungal communities associated with tree roots were compared at 20-cm distances from P. sakuraii shoots between the two habitats by molecular identification of AM fungal partial sequences of the small subunit ribosomal RNA gene. The percentage of AM fungal sequences showing over 99 % identity with those of the dominant P. sakuraii mycobionts was high (54.9 %) in Nagiso, but low (13.2 %) in Sengenyama. Accordingly, the abundance of P. sakuraii seems to reflect the proportion of potential mycobionts. It is likely that P. sakuraii mycobionts are not rare in Japanese warm temperate forests since 11.2 % of AM fungal sequences previously obtained from a deciduous broad-leaved forest devoid of P. sakuraii in Mizuho, central Honshu, Japan, were >99 % identical to those of the dominant P. sakuraii mycobionts. Thus, results suggest that the abundant mycobionts may be required for sufficient propagation of P. sakuraii, and this quantitative trait of AM fungal communities required for P. sakuraii may explain the rarity of this plant. PMID- 26846144 TI - 14-3-3 Proteins regulate Akt Thr308 phosphorylation in intestinal epithelial cells. AB - Akt activation has been associated with proliferation, differentiation, survival and death of epithelial cells. Phosphorylation of Thr308 of Akt by phosphoinositide-dependent kinase 1 (PDK1) is critical for optimal stimulation of its kinase activity. However, the mechanism(s) regulating this process remain elusive. Here, we report that 14-3-3 proteins control Akt Thr308 phosphorylation during intestinal inflammation. Mechanistically, we found that IFNgamma and TNFalpha treatment induce degradation of the PDK1 inhibitor, 14-3-3eta, in intestinal epithelial cells. This mechanism requires association of 14-3-3zeta with raptor in a process that triggers autophagy and leads to 14-3-3eta degradation. Notably, inhibition of 14-3-3 function by the chemical inhibitor BV02 induces uncontrolled Akt activation, nuclear Akt accumulation and ultimately intestinal epithelial cell death. Our results suggest that 14-3-3 proteins control Akt activation and regulate its biological functions, thereby providing a new mechanistic link between cell survival and apoptosis of intestinal epithelial cells during inflammation. PMID- 26846149 TI - Central and peripheral pathogenetic forms of type 2 diabetes: a proof-of-concept study. AB - HYPOTHESIS: Previous studies provide evidence that glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) should not be considered as interchangeable alternatives in the diagnosis of the same type 2 diabetes, but as indicators of its different pathogenetic subtypes. This study was conducted to determine whether a particularly high amount of glucose in either HbA1c form or in fasting plasma would be found in diabetic patients genetically predisposed for either intensive cognitive or intensive muscle metabolic activity, respectively. METHODS: HbA1c and FPG levels, polymorphisms of genes indicating the predisposition to different cognitive activity (the dopamine D2 receptor (DRD2/ANKK1)), muscle activity (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC1A(PPARGC1A))), and vascular regulation of general metabolic activity (the angiotensin 1 converting enzyme (ACE)) were assessed in diabetic patients and nondiabetic controls. RESULTS: DRD2/ANKK1 polymorphism that affects baseline central arousal determined HbA1c variations uncorrelated with FPG in total and clinical groups. The mutation of PGC1A mainly affecting peripheral glucose metabolism had an effect on FPG correlated or uncorrelated with HbA1c depending on the effect assessment in the total sample or in the nondiabetic group, respectively. ACE insertion/deletion (I/D) gene polymorphism was associated with both HbA1c and FPG fluctuations, but only in diabetic patients. CONCLUSION: The findings provide evidence that the HbA1c and FPG may predict the risks for different subtypes of type 2 diabetes associated with either brain or muscle metabolic activity in genetically vulnerable people. PMID- 26846148 TI - Is the root-colonizing endophyte Acremonium strictum an ericoid mycorrhizal fungus? AB - In previous investigations, we found that Acremonium strictum (strain DSM 100709) developed intracellular structures with similarity to mycelia of ericoid mycorrhizal fungi in the rhizodermal cells of flax plants and in hair roots of Rhododendron plantlets. A. strictum had also been isolated from roots of ericaceous salal plants and was described as an unusual ericoid mycorrhizal fungus (ERMF). As its mycorrhizal traits were doubted, we revised the hypothesis of a mycorrhizal nature of A. strictum. A successful synthesis of mycorrhiza in hair roots of inoculated ericaceous plants was a first step of evidence, followed by fluorescence microscopy with FUN((r))1 cell stain to observe the vitality of the host cells at the early infection stage. In inoculation trials with in vitro raised mycorrhiza-free Rhododendron plants in axenic liquid culture and in greenhouse substrate culture, A. strictum was never observed in living hair root cells. As compared to the ERMF Oidiodendron maius and Rhizoscyphus ericae that invaded metabolically active host cells and established a symbiotic unit, A. strictum was only found in cells that were dead or in the process of dying and in the apoplast. In conclusion, A. strictum does not behave like a common ERMF-if it is one at all. A comparison of A. strictum isolates from ericaceous and non ericaceous hosts could reveal further identity details to generalize or specify our findings on the symbiotic nature of A. strictum. At least, the staining method enables to discern between true mycorrhizal and other root endophytes-a tool for further studies. PMID- 26846150 TI - Giant Cell Arteritis as a Cause of Myocarditis and Atrial Fibrillation. PMID- 26846152 TI - Benzimidazole resistance in Nematodirus spathiger and N. filicollis in New Zealand. AB - AIM: To determine the prevalence of benzimidazole resistance in Nematodirus spathiger and N. filicollis from a sample of New Zealand farms. METHODS: The efficacy of albendazole (ABZ) against Nematodirus spp. was assessed by faecal nematode egg count reduction (FECR) tests undertaken in lambs aged 3-8 months old on 27 sheep farms throughout New Zealand. On each farm, groups of 10-16 lambs were either treated with ABZ (4.75 mg/kg) or remained as untreated controls. Faecal samples were collected from all animals at the time of treatment and 7-10 days later. Faecal nematode egg counts (FEC) were performed using a modified McMaster technique. Larvae were cultured from pooled faecal samples, collected 7 10 days after treatment from each group, by incubation at 20 degrees C for 6 weeks, 4 degrees C for 26 weeks then 13 degrees C for 2 weeks. The resulting third stage larvae were identified to species using a multiplex PCR assay, that identified species-specific sequences in the second internal transcribed spacer region of ribosomal DNA. The efficacy of ABZ for N. spathiger and N. filicollis was calculated from the proportion of the two species in culture and the group mean FEC before and after treatment. Only farms with a mean of 10 epg for each species in untreated samples were included for analysis. Resistance was defined as an efficacy <95%. RESULTS: On farms that met the threshold of 10 epg in faecal samples, benzimidazole resistance was found on 20/21 (95%) farms for N. spathiger compared with 4/10 (40%) farms for N. filicollis (p<0.05). In samples collected following treatment, a mean of 83 (min 46, max 100)% of Nematodirus spp. larvae recovered from the untreated groups were N. spathiger, compared with 94 (min 45, max 100)% in the ABZ treated groups (p=0.03). This change in percentage was not influenced by the overall efficacy of treatment based on the FECR test (p=0.324). CONCLUSION: The results confirm the high level of resistance in N. spathiger in New Zealand and that benzimidazole resistance was more common in N. spathiger than N. filicollis. While resistance to benzimidazole anthelmintics has been reported previously in New Zealand, this is the first report of N. filicollis being resistant to benzimidazole anthelmintics. PMID- 26846151 TI - High prevalence of extra-genital chlamydial or gonococcal infections among men who have sex with men and transgender women in Lima, Peru. AB - Chlamydia trachomatis and Neisseria gonorrhoeae are among the most common sexually transmitted bacterial infections in the world. Data are limited, however, on the burden of extra-genital chlamydial and gonococcal infections among men who have sex with men and transgender women in Lima, Peru. Data were gathered from self-collected anal or pharyngeal swabs from participants in Lima, Peru, and analyzed via cross-sectional methods. Prevalence ratios for the association between extra-genital infection with socio-demographic and sexual behaviors were determined. Overall, 127 (32.8%) participants had anal or pharyngeal infections. On multivariate modeling, anal infection was positively associated with practicing both receptive and insertive anal sex, when compared to insertive alone (PR = 2.49; 95% CI = 1.32-4.71), and negatively associated with any antibiotic use in the prior three months (PR = 0.60; 95% CI = 0.39 0.91). Pharyngeal infection was negatively associated with age greater than 30 years compared to 18-30 years (PR = 0.54; 95% CI = 0.30-0.96), and positively associated with gender identity of transgender women (PR = 2.12; 95% CI = 1.20 3.73). This study demonstrates considerable burden of extra-genital chlamydial and gonococcal infections among men who have sex with men and transgender women in Lima, Peru. PMID- 26846154 TI - Synthesis and Cytotoxic Evaluation of Monocarbonyl Analogs of Curcumin as Potential Anti-Tumor Agents. AB - Preclinical Research A series of mono-carbonyl curcumin analogs with different substituents at the 4/4'-position of the phenyl group were synthesized and screened for in vitro cytotoxicity against a panel of human cancer cell lines using a methyl thiazolyl tetrazolium assay. Several of the curcumin analogs, especially B114, exhibited a wide-spectrum of anti-tumor properties in all tested cell lines, indicating their potential in as anti-cancer lead compounds. Further toxicity testing in the NRK-52E kidney cell line revealed that the analogs A111, A113, and B114 had comparable or higher safety than curcumin. These data suggested that the introduction of appropriate substituents in the 4/4'-positions could be a promising approach for curcumin-based drug design. PMID- 26846153 TI - Norcantharidin Suppresses Colon Cancer Cell Epithelial-Mesenchymal Transition by Inhibiting the alphavbeta6-ERK-Ets1 Signaling Pathway. AB - Norcantharidin (NCTD) is an efficacious anti-cancer drug that has been used in China for many years, but its underlying mechanism of action is still not fully understood. In the present study, we found that NCTD could induce morphological changes in colon cancer cells, causing a transition from a spindle-shaped morphology to a typical round or oval shape, which was indicative of a mesenchymal-epithelial transition (MET) process. Next, we investigated the mechanism by which NCTD induced the MET process. Using a transwell assay, we found that NCTD could suppress the migratory and invasive ability of colon cancer cells in a dose-dependent manner. Moreover, NCTD suppressed the expression of integrin alphavbeta6, MMP-3, and MMP-9 as well as the polymerization of F-actin, further supporting its suppressive effect on migratory and invasive ability. Furthermore, the expression of alphavbeta6, N-cadherin, vimentin and phosphorylated ERK was decreased, while the expression of E-cadherin was up regulated. We verified that phosphorylated Ets1 was down-regulated substantially after treatment with NCTD. Taken together, our data demonstrated that NCTD could inhibit the EMT process of colon cancer cells by inhibiting the alphavbeta6-ERK Ets1 signaling pathway. This study revealed part of the mechanism through which NCTD could reverse the EMT process in colon cancer. PMID- 26846156 TI - The natural history of growth in patients with Hunter syndrome: Data from the Hunter Outcome Survey (HOS). AB - Hunter syndrome (mucopolysaccharidosis type II) affects growth but the overall impact is poorly understood. This study investigated the natural history of growth and related parameters and their relationship with disease severity (as indicated by cognitive impairment). Natural history data from males followed prospectively in the Hunter Outcome Survey registry and not receiving growth hormone or enzyme replacement therapy, or before treatment start, were analysed (N=676; January 2014). Analysis of first-reported measurements showed short stature by 8years of age; median age-corrected standardized height score (z score) in patients aged 8-12years was -3.1 (1st, 3rd quartile: -4.3, -1.7; n=68). Analysis of growth velocity using consecutive values found no pubertal growth spurt. Patients had large head circumference at all ages, and above average body weight and body mass index (BMI) during early childhood (median z-score in patients aged 2-4years, weight [n=271]: 1.7 [0.9, 2.4]; BMI [n=249]: 2.0 [1.1, 2.7]). Analysis of repeated measurements over time found greater BMI in those with cognitive impairment than those without, but no difference in height, weight or head circumference. Logistic regression modelling (data from all time points) found that increased BMI was associated with the presence of cognitive impairment (odds ratio [95% CI], 3.329 [2.313-4.791]), as were increased weight (2.365 [1.630-3.433]) and head circumference (1.749 [1.195-2.562]), but not reduced height. Unlike some other MPS disorders, there is no evidence at present for predicting disease severity in patients with Hunter syndrome based on changes in growth characteristics. PMID- 26846158 TI - What drives operational performance in clinical R&D? PMID- 26846159 TI - Radiation recall pneumonitis induced by erlotinib after palliative thoracic radiotherapy for lung cancer: Case report and literature review. AB - Radiation lung injury usually develops 1-6 months after cessation of radiation therapy to the lung. Acute change in the previously irradiated lung after administration of antineoplastic agent is known as radiation recall pneumonitis. Erlotinib is a reversible epidemal growth factor receptor tyrosine kinase inhibitor, which is effective for patients with advanced lung cancer with epidermal growth factor receptor mutations. Here we report a rare case of radiation recall pneumonitis following treatment with erlotinib 4 months after palliative radiotherapy to the lung. A 76-year-old man with non-small cell lung cancer was treated with polychemotherapy, palliative thoracic irradiation (30 Gy in 12 fractions) and erlotinib thereafter. Two months after administration of erlotinib he developed of severe dyspnea, cough, anorexia and lack of energy. CT chest revealed extensive radiation pneumonitis. Erlotinib was ceased and high dose steroids were started. The symptoms ultimately resolved and erlotinib was resumed cautiously after 11 weeks. On dosimetric analysis, lung V20 and the mean lung dose were 20.33% and 10.7 Gy, respectively, and hence, the risk of radiation pneumonitis is very low. These data indicate that systemic administration of erlotinib after low-dose palliative radiation therapy can be associated with unexpected toxicity when visceral organs are within the radiation field. PMID- 26846157 TI - The NIH Undiagnosed Diseases Program and Network: Applications to modern medicine. AB - INTRODUCTION: The inability of some seriously and chronically ill individuals to receive a definitive diagnosis represents an unmet medical need. In 2008, the NIH Undiagnosed Diseases Program (UDP) was established to provide answers to patients with mysterious conditions that long eluded diagnosis and to advance medical knowledge. Patients admitted to the NIH UDP undergo a five-day hospitalization, facilitating highly collaborative clinical evaluations and a detailed, standardized documentation of the individual's phenotype. Bedside and bench investigations are tightly coupled. Genetic studies include commercially available testing, single nucleotide polymorphism microarray analysis, and family exomic sequencing studies. Selected gene variants are evaluated by collaborators using informatics, in vitro cell studies, and functional assays in model systems (fly, zebrafish, worm, or mouse). INSIGHTS FROM THE UDP: In seven years, the UDP received 2954 complete applications and evaluated 863 individuals. Nine vignettes (two unpublished) illustrate the relevance of an undiagnosed diseases program to complex and common disorders, the coincidence of multiple rare single gene disorders in individual patients, newly recognized mechanisms of disease, and the application of precision medicine to patient care. CONCLUSIONS: The UDP provides examples of the benefits expected to accrue with the recent launch of a national Undiagnosed Diseases Network (UDN). The UDN should accelerate rare disease diagnosis and new disease discovery, enhance the likelihood of diagnosing known diseases in patients with uncommon phenotypes, improve management strategies, and advance medical research. PMID- 26846160 TI - Analysis of 2013 European LeukaemiaNet (ELN) responses in chronic phase CML across four frontline TKI modalities and impact on clinical outcomes. AB - This study assessed the relevance of 2013 European LeukaemiaNet (ELN) response categories on patients treated with common frontline tyrosine kinase inhibitors (TKI) in chronic myeloid leukaemia in chronic phase (CML-CP). Four hundred and eighty-seven patients treated with imatinib (400 mg; IM 400, n = 70; 800 mg; IM800, n = 201), dasatinib (n = 107) or nilotinib (n = 109) were analysed. Intention to treat (ITT) analysis indicated that the proportion of patients falling into optimal, warning and failure ELN categories were 89%, 6%, 6% at 3 months, 78%, 17% and 6% at 6 months, and 75%, 13% and 13% at 12 months, respectively. Rates of optimal response at 3 months were 75% for IM400, 90% for IM800, 89% for dasatinib and 97% for nilotinib; 41%, 80%, 86% and 89% at 6 months; and 47%, 77%, 76% and 87% at 12 months, respectively. Patients achieving optimal response had longer eventfree (EFS), failurefree (FFS), transformationfree (TFS) and overall survival (OS) compared to warning and failure responses at all-time points. Treatment with imatinib 800, dasatinib or nilotinib predicted for achieving an optimal response. Optimal response predicted for significantly longer EFS, FFS, TFS and OS at 3, 6 and 12 months, irrespective of the TKI modality used. ELN response categories reliably predicted outcomes in CML patients receiving commonly used TKIs. PMID- 26846161 TI - Polymeric Nanoparticles Amenable to Simultaneous Installation of Exterior Targeting and Interior Therapeutic Proteins. AB - Effective delivery of therapeutic proteins is a formidable challenge. Herein, using a unique polymer family with a wide-ranging set of cationic and hydrophobic features, we developed a novel nanoparticle (NP) platform capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside by a self-assembly procedure. The loaded therapeutic proteins (e.g., insulin) within the NPs exhibited sustained and tunable release, while the surface-coated protein ligands (e.g., transferrin) were demonstrated to alter the NP cellular behaviors. In vivo results revealed that the transferrin-coated NPs can effectively be transported across the intestinal epithelium for oral insulin delivery, leading to a notable hypoglycemic response. PMID- 26846162 TI - What Predicts Patients' Willingness to Undergo Online Treatment and Pay for Online Treatment? Results from a Web-Based Survey to Investigate the Changing Patient-Physician Relationship. AB - BACKGROUND: Substantial research has focused on patients' health information seeking behavior on the Internet, but little is known about the variables that may predict patients' willingness to undergo online treatment and willingness to pay additionally for online treatment. OBJECTIVE: This study analyzed sociodemographic variables, psychosocial variables, and variables of Internet usage to predict willingness to undergo online treatment and willingness to pay additionally for online treatment offered by the general practitioner (GP). METHODS: An online survey of 1006 randomly selected German patients was conducted. The sample was drawn from an e-panel maintained by GfK HealthCare. Missing values were imputed; 958 usable questionnaires were analyzed. Variables with multi-item measurement were factor analyzed. Willingness to undergo online treatment and willingness to pay additionally for online treatment offered by the GP were predicted using 2 multiple regression models. RESULTS: Exploratory factor analyses revealed that the disposition of patients' personality to engage in information-searching behavior on the Internet was unidimensional. Exploratory factor analysis with the variables measuring the motives for Internet usage led to 2 separate factors: perceived usefulness (PU) of the Internet for health related information searching and social motives for information searching on the Internet. Sociodemographic variables did not serve as significant predictors for willingness to undergo online treatment offered by the GP, whereas PU (B=.092, P=.08), willingness to communicate with the GP more often in the future (B=.495, P<.001), health-related information-seeking personality (B=.369, P<.001), actual use of online communication with the GP (B=.198, P<.001), and social motive (B=.178, P=.002) were significant predictors. Age, gender, satisfaction with the GP, social motive, and trust in the GP had no significant impact on the willingness to pay additionally for online treatment, but it was predicted by health-related information-seeking personality (B=.127, P=.07), PU (B=-.098, P=.09), willingness to undergo online treatment (B=.391, P<.001), actual use of online communication with the GP (B=.192, P=.001), highest education level (B=.178, P<.001), monthly household net income (B=.115, P=.01), and willingness to communicate with the GP online more often in the future (B=.076, P=.03). CONCLUSIONS: Age, gender, and trust in the GP were not significant predictors for either willingness to undergo online treatment or to pay additionally for online treatment. Willingness to undergo online treatment was partly determined by the actual use of online communication with the GP, willingness to communicate online with the GP, health information-seeking personality, and social motivation for such behavior. Willingness to pay extra for online treatment was influenced by the monthly household net income category and education level. The results of this study are useful for online health care providers and physicians who are considering offering online treatments as a viable number of patients would appreciate the possibility of undergoing an online treatment offered by their GP. PMID- 26846163 TI - Combining multiple features for error detection and its application in brain computer interface. AB - BACKGROUND: Brain-computer interface (BCI) is an assistive technology that conveys users' intentions by decoding various brain activities and translating them into control commands, without the need of verbal instructions and/or physical interactions. However, errors existing in BCI systems affect their performance greatly, which in turn confines the development and application of BCI technology. It has been demonstrated viable to extract error potential from electroencephalography recordings. METHODS: This study proposed a new approach of fusing multiple-channel features from temporal, spectral, and spatial domains through two times of dimensionality reduction based on neural network. 26 participants (13 males, mean age = 28.8 +/- 5.4, range 20-37) took part in the study, who engaged in a P300 speller task spelling cued words from a 36-character matrix. In order to evaluate the generalization ability across subjects, the data from 16 participants were used for training and the rest for testing. RESULTS: The total classification accuracy with combination of features is 76.7 %. The receiver operating characteristic (ROC) curve and area under ROC curve (AUC) further indicate the superior performance of the combination of features over any single features in error detection. The average AUC reaches 0.7818 with combined features, while 0.7270, 0.6376, 0.7330 with single temporal, spectral, and spatial features respectively. CONCLUSIONS: The proposed method combining multiple-channel features from temporal, spectral, and spatial domain has better classification performance than any individual feature alone. It has good generalization ability across subject and provides a way of improving error detection, which could serve as promising feedbacks to promote the performance of BCI systems. PMID- 26846164 TI - Label-free detection and manipulation of single biological nanoparticles. AB - In the past several years, there have been significant advances in the field of nanoparticle detection for various biological applications. Of considerable interest are synthetic nanoparticles being designed as potential drug delivery systems as well as naturally occurring or biological nanoparticles, including viruses and extracellular vesicles. Many infectious diseases and several human cancers are attributed to individual virions. Because these particles likely display different degrees of heterogeneity under normal physiological conditions, characterization of these natural nanoparticles with single-particle sensitivity is necessary for elucidating information on their basic structure and function as well as revealing novel targets for therapeutic intervention. Additionally, biodefense and point-of-care clinical testing demand ultrasensitive detection of viral pathogens particularly with high specificity. Consequently, the ability to perform label-free virus sensing has motivated the development of multiple electrical-, mechanical-, and optical-based detection techniques, some of which may even have the potential for nanoparticle sorting and multi-parametric analysis. For each technique, the challenges associated with label-free detection and measurement sensitivity are discussed as are their potential contributions for future real-world applications. WIREs Nanomed Nanobiotechnol 2016, 8:717-729. doi: 10.1002/wnan.1392 For further resources related to this article, please visit the WIREs website. PMID- 26846165 TI - Comparative transcriptomics and comprehensive marker resource development in mulberry. AB - BACKGROUND: High potential of Morus laevigata and Morus serrata has been proposed in the breeding programs for Morus sp. However, due to the lack of dense molecular markers this goal is still in its nascent stage and not yet realized. We thus, sequenced the transcriptomes of these two wild Morus species and utilized the data for marker development. RESULTS: We generated 87.0 and 80.3 Mb of transcriptome data from M. laevigata and M. serrata, respectively. The transcriptomes from M. laevigata and M. serrata, were assembled into 95,181 and 85,269 transcripts, respectively, and annotated. We identified around 24,049 Simple Sequence Repeats (SSRs), 1,201,326 Single Nucleotide Polymorphisms (SNPs) and 67,875 Insertion-Deletions (InDels). The variants having a higher impact were also identified and their effect was further investigated. CONCLUSIONS: The transcriptome resource from the wildly growing mulberry species developed in this study can find wide applicability in gene identification and/or characterization. It can also contribute immensely in the existing mulberry improvement programs. PMID- 26846166 TI - Patients Receiving Integrative Medicine Effectiveness Registry (PRIMIER) of the BraveNet practice-based research network: study protocol. AB - BACKGROUND: Integrative medicine (IM) provides patient-centered care and addresses the full range of physical, emotional, mental, social, spiritual, and environmental influences that affect a person's health. IM is a "whole systems" approach that employs multiple modalities as opposed to an isolated complementary therapy. Thus, studying outcomes of IM is more challenging than evaluating an isolated intervention. Practice-based research networks (PBRNs) allow for clinicians/investigators at multiple diverse sites using common methodology to pool their data, increase participant sample size and increase generalizability of results. To conduct real-world, practice-based research, the Bravewell Collaborative founded BraveNet in 2007 as the first national integrative medicine PBRN. METHODS AND DESIGN: Patients Receiving Integrative Medicine Effectiveness Registry (PRIMIER) is a prospective, non-randomized, observational evaluation conducted at fourteen clinical sites. Participants receive a non-standardized, personalized, multimodal IM approach for various medical conditions. Using the REDCap electronic platform, an anticipated 10,000 study participants will complete patient-reported outcome measures including Patient Reported Outcomes Measurement Information System (PROMIS)-29, Perceived Stress Scale-4, and the Patient Activation Measure at baseline, 2, 4, 6, 12, 18 and 24 months. Extractions from participants' electronic health records include IM services received, as well as ICD diagnostic codes, and CPT billing codes associated with each IM visit. Repeated-measures analyses will be performed on data to assess change from baseline through 24 months with planned subgroup analyses to include specific clinical population and specific IM intervention or combinations. DISCUSSION: As the PRIMIER registry grows, we anticipate that our results would provide an indication of the promise of PBRN research efforts in IM. Analyses will incorporate a large sample of participants and an expected 10-year observation period and will provide the ability to evaluate the effect of IM on outcomes for specific clinical populations and specific IM interventions or combinations. As such, PRIMIER will serve as a national platform for future evaluations of IM best practices. TRIAL REGISTRATION: Clinical Trials.gov NCT01754038. PMID- 26846168 TI - Asymmetric Hydrogenation of Vinylthioethers: Access to Optically Active 1,5 Benzothiazepine Derivatives. AB - A novel asymmetric hydrogenation of vinylthioethers was developed using a ruthenium(II) NHC complex. This method provides an efficient approach to optically active 1,5-benzothiazepines featuring stereocenters with C-S bonds. Excellent enantioselectivities (up to 95 % ee) and high yields (up to 99 %) were obtained for a variety of substrates bearing a range of useful functional groups. Moreover, this methodology could be directly applied to the synthesis of the antidepressant drug R-(-)-thiazesim. PMID- 26846169 TI - Investigating the Heterogeneous Interaction of VOCs with Natural Atmospheric Particles: Adsorption of Limonene and Toluene on Saharan Mineral Dusts. AB - The heterogeneous interaction of limonene and toluene with Saharan dusts was investigated under dark conditions, pressure of 1 atm, and temperature 293 K. The mineral dust samples were collected from six different regions along the Sahara desert, extending from Tunisia to the western Atlantic coastal areas of Morocco, and experiments were carried out with the smallest sieved fractions, that is, inferior to 100 MUm. N2 sorption measurements, granulometric analysis, and X-ray fluorescence and diffraction (XRF and XRD) measurements were conducted to determine the physicochemical properties of the particles. The chemical characterization showed that dust originating from mideastern Sahara has a significantly higher SiO2 content (~ 82%) than dust collected from the western coastal regions where the SiO2 relative abundance was ~ 50%. A novel experimental setup combining diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), selected-ion flow-tube mass spectrometry (SIFT-MS), and long path transmission Fourier transform infrared spectroscopy (FTIR) allowed us to follow both the adsorbed and gas phases. The kinetic adsorption/desorption measurements were performed using purified dry air as bath gas, exposing each dust surface to 10 ppm of the selective volatile organic compound (VOC). The adsorption of limonene was independent of the SiO2 content, given the experimental uncertainties, and the coverage measurements ranged between (10 and 18) * 10(13) molecules cm(-2). Experimental results suggest that other metal oxides that could possibly influence dust acidity may enhance the adsorption of limonene. On the contrary, in the case of toluene, the adsorption capacities of the Saharan samples increased with decreasing SiO2 content; however, the coverage measurements were significantly lower than those of limonene and ranged between (2 and 12) * 10(13) molecules cm(-2). Flushing the surface with purified dry air showed that VOC desorption is not a completely reversible process at room temperature. The reversibly adsorbed fraction and the rate coefficients of desorption, kdes, depended inversely on the SiO2 relative abundance for both VOCs. PMID- 26846167 TI - Establishment of feeder-free culture system for human induced pluripotent stem cell on DAS nanocrystalline graphene. AB - The maintenance of undifferentiated human pluripotent stem cells (hPSC) under xeno-free condition requires the use of human feeder cells or extracellular matrix (ECM) coating. However, human-derived sources may cause human pathogen contamination by viral or non-viral agents to the patients. Here we demonstrate feeder-free and xeno-free culture system for hPSC expansion using diffusion assisted synthesis-grown nanocrystalline graphene (DAS-NG), a synthetic non biological nanomaterial which completely rule out the concern of human pathogen contamination. DAS-NG exhibited advanced biocompatibilities including surface nanoroughness, oxygen containing functional groups and hydrophilicity. hPSC cultured on DAS-NG could maintain pluripotency in vitro and in vivo, and especially cell adhesion-related gene expression profile was comparable to those of cultured on feeders, while hPSC cultured without DAS-NG differentiated spontaneously with high expression of somatic cell-enriched adhesion genes. This feeder-free and xeno-free culture method using DAS-NG will facilitate the generation of clinical-grade hPSC. PMID- 26846170 TI - Atorvastatin in improvement of cognitive impairments caused by amyloid beta in mice: involvement of inflammatory reaction. AB - BACKGROUND: The production of inflammatory cytokines resulting from amyloid beta (Abeta) is associated with the initiation of Alzheimer's disease (AD). Atorvastatin (ATV) has been reported to improve AD, however, it is unclear how the anti-inflammatory mechanism is linked with its protection against the impairment of spatial cognitive function in AD. The present study was designed to explore what mechanism was possibly involved in the anti-inflammatory pathway in regard to the ATV treatment of AD. METHODS: We used an AD model induced by the administration of Abeta(25-35) in male C57BL/6 mice and an in vitro culture system to study the protective effects of ATV on the spatial cognitive deficits, hippocampal long-term potentiation (LTP) impairment and inflammatory reaction. RESULTS: The intragastric administration of ATV (5 mg/kg) in Abeta(25-35)-treated mice significantly ameliorated the spatial cognitive deficits and prevented the LTP impairment in hippocampal CA1. The increased Iba-1 positive cells and inflammatory components in the hippocampus were reduced after the ATV treatment. The anti-inflammatory and LTP protection of ATV were abolished using the replenishment of farnesyl pyrophosphate by the administration of farnesol (FOH). The hippocampal slices culture showed Abeta(25-35)-induced neurotoxicity in the absence of the presence of ATV. Treatment with ATV (0.5, 1, 2.5 MUmol/L) dose dependently prevented the cell damage in hippocampus induced by Abeta25-35. CONCLUSION: The administration of ATV ameliorated the cognitive deficits, depressed the inflammatory responses, improved the LTP impairment, and prevents Abeta25-35-induced neurotoxicity in cultured hippocampal neurons. These protective functions of ATV involved the pathway of reducing farnesyl pyrophosphate (FPP). PMID- 26846171 TI - SEPT7 overexpression inhibits glioma cell migration by targeting the actin cytoskeleton pathway. AB - Glioma cell metastasis is a serious obstacle for surgical treatment and prognosis, of which locomotion of the cytoskeleton is a key contributor of cancer cell spreading. SEPT7 is documented as a cytoskeletal protein with GTPase activity and involved in glioma progression. However, the underlying mechanism of SEPT7 in glioma invasion remains unresolved. Our study investigated whether SEPT7 influences glioma cell migration involved in cytoskeleton modulation. The SEPT7 expression in various glioma cell lines was markedly decreased compared to in normal human brain cells. It was demonstrated that SEPT7 overexpression significantly inhibits LN18 cell migration and chemotaxis induced by IGF-1 (P<0.01 and P<0.01). Moreover, MMP-2 and MMP-9 were dramatically depressed after SEPT7 upregulation. To understand the mechanisms by which SEPT7 modulates homeostasis of the actin cytoskeleton, the F-actin/G-actin ratio and cofilin expression were determined. The data revealed that the F-actin/G-actin ratio and cofilin were reduced, and p-cofilin increased conversely in cells with SEPT7 overexpression, indicating that SEPT7 reduced glioma cell migration by promoting cofilin phosphorylation and depolymerizing actin. Then, to understand the role of cofilin in SEPT7-mediated actin dynamic equilibrium and cell migration, cofilin siRNA was transfected into cells. Surprisingly, cell migration and actin polymerization which had been improved by SEPT7 siRNA were significantly reversed, and the accompanying cofilin phosphorylation increased, indicating that cofilin phospho-regulation played an important role in SEPT7-mediated cytoskeleton locomotion and glioma cell migration. In conclusion, SEPT7 is involved in glioma cell migration with the assistance of cofilin phospho-mediated cytoskeleton locomotion. PMID- 26846173 TI - Modelling end-of-life care practices: Factors associated with critical care nurse engagement in care provision. AB - OBJECTIVE: To identify factors associated with critical care nurses' engagement in end-of-life care practices. METHODS: Multivariable regression modelling was undertaken on 392 responses to an online self-report survey of end-of-life care practices and factors influencing practice by Australian critical care nurses'. Univariate general linear models were built for six end-of-life care practice areas. RESULTS: Six statistically significant (p<0.001) models were developed: Information sharing F(3, 377)=40.53, adjusted R(2) 23.8%; Environmental modification F(5, 380)=19.55, adjusted R(2) 19.4%; Emotional support F(10, 366)=12.10, adjusted R(2) 22.8%; Patient and family centred decision making F(8, 362)=17.61 adjusted R(2) 26.4%; Symptom management F(8, 376)=7.10, adjusted R(2) 11.3%; and Spiritual support F(9, 367)=14.66, adjusted R(2) 24.6%. Stronger agreement with values consistent with a palliative approach, and greater support for patient and family preferences were associated with higher levels of engagement in end-of-life care practices. Higher levels of preparedness and access to opportunities for knowledge acquisition were associated with engagement in the interpersonal practices of patient and family centred decision making and emotional support. CONCLUSION: This study provides evidence for interventions to address factors associated with nurse engagement to increase participation in all end-of-life care practice areas. PMID- 26846174 TI - Models and Data Sources Used in Systems Medicine. A Systematic Literature Review. AB - BACKGROUND: Systems medicine is a new approach for the development and selection of treatment strategies for patients with complex diseases. It is often referred to as the application of systems biology methods for decision making in patient care. For systems medicine computer applications, many different data sources have to be integrated and included into models. This is a challenging task for Medical Informatics since the approach exceeds traditional systems like Electronic Health Records. To prioritize research activities for systems medicine applications, it is necessary to get an overview over modelling methods and data sources already used in this field. OBJECTIVES: We performed a systematic literature review with the objective to capture current use of 1) modelling methods and 2) data sources in systems medicine related research projects. METHODS: We queried the MEDLINE and ScienceDirect databases for papers associated with the search term systems medicine and related terms. Papers were screened and assessed in full text in a two-step process according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. RESULTS: The queries returned 698 articles of which 34 papers were finally included into the study. A multitude of modelling approaches such as machine learning and network analysis was identified and classified. Since these approaches are also used in other domains, no methods specific for systems medicine could be identified. Omics data are the most widely used data types followed by clinical data. Most studies only include a rather limited number of data sources. CONCLUSIONS: Currently, many different modelling approaches are used in systems medicine. Thus, highly flexible modular solutions are necessary for systems medicine clinical applications. However, the number of data sources included into the models is limited and most projects currently focus on prognosis. To leverage the potential of systems medicine further, it will be necessary to focus on treatment strategies for patients and consider a broader range of data. PMID- 26846172 TI - A long journey coming to fruition: In sight of the preselection T-cell repertoire. AB - In addition to MHC restriction and its structural correlate the recognition of an MHC-peptide complex by the TCR, T-cell reactivity is constrained by positive and negative selection in the thymus. While mouse genetic studies have provided compelling evidence for both processes, the actual impact of selection on the mature T-cell repertoire has remained difficult to assess, in particular because it has so far not been possible to follow the intrathymic differentiation of antigen-specific T cells carrying endogenous TCR specificities. In this issue of the European Journal of Immunology, Hesnard et al. [Eur. J. Immunol. 2016. 46: 560-569] report the detection of human antigen-specific immature thymocytes, thereby opening the way to addressing these questions. Here, we discuss the implications of this technological advance. PMID- 26846175 TI - MicroRNA-98 suppresses cell proliferation, migration and invasion by targeting collagen triple helix repeat containing 1 in hepatocellular carcinoma. AB - MicroRNAs (miRNAs) are emerging as critical regulators in carcinogenesis and tumor progression. miR-98 has previously been verified to be important in tumor progression, however, its function in hepatocellular carcinoma (HCC) remains to be elucidated. The expression levels of miR-98 in HCC tissues and cell lines were determined by reverse transcription quantitative polymerase chain reaction. Subsequently, the effect of miR-98 on cell proliferation, migration and invasion was evaluated by MTT assay, transwell migration assay and transwell invasion assay. Furthermore, a luciferase reporter assay was conducted to confirm the action of miR-98 on downstream target genes, including collagen triple helix repeat containing 1 (CTHRC1). In the present study, it was confirmed that miR-98 was significantly downregulated in HCC tissues and cell lines. Overexpression of miR-98 inhibited HCC cell proliferation, migration and invasion in vitro. In addition, at the molecular level, the tumor oncogene CTHRC1 was identified to be the direct target of miR-98. Our findings suggested that miR-98 was significantly downregulated in HCC and suppressed HCC cell proliferation, migration and invasion partially via the downregulation of CTHRC1. Thus, these data demonstrated that miR-98 could be a potential therapeutic target in HCC. PMID- 26846177 TI - Factors associated with failure to complete adjuvant chemotherapy in pancreatic cancer. AB - BACKGROUND: The importance of completing adjuvant chemotherapy in pancreatic cancer is becoming recognized. However, the clinicopathological factors associated with failure to complete adjuvant chemotherapy remain unclear. METHODS: A total of 135 patients were analyzed to identify the factors associated with failure to complete adjuvant chemotherapy. RESULTS: Ninety patients completed planned adjuvant chemotherapy, whereas 45 patients failed to complete adjuvant chemotherapy. Lower preoperative prognostic nutritional index, intraoperative blood transfusion, and organ and/or space surgical site infection, and advanced tumor stage were associated with failure to complete adjuvant chemotherapy. Neoadjuvant chemoradiotherapy was associated with significantly lower prognostic nutritional index, less incidence of organ and/or space surgical site infection, and earlier tumor stage, suggesting the conflicting effects of neoadjuvant chemoradiotherapy on completing adjuvant chemotherapy. CONCLUSIONS: Several clinicopathological factors including patient conditions and perioperative events were associated with failure to complete adjuvant chemotherapy. PMID- 26846176 TI - Evaluating disparities in inpatient surgical cancer care among American Indian/Alaska Native patients. AB - BACKGROUND: American Indian/Alaska Native (AI/AN) patients with cancer have the lowest survival rates of all racial and ethnic groups, possibly because they are less likely to receive "best practice" surgical care than patients of other races. METHODS: Prospective cohort study comparing adherence with generic and cancer-specific guidelines on processes of surgical care between AI/AN and non Hispanic white (NHW) patients in Washington State (2010 to 2014) was conducted. RESULTS: A total of 156 AI/AN and 6,030 NHW patients underwent operations for 10 different cancers, and had similar mean adherence to generic surgical guidelines (91.5% vs 91.9%, P = .57). AI/AN patients with breast cancer less frequently received preoperative diagnostic core needle biopsy (81% vs 94%, P = .004). AI/AN patients also less frequently received care adherent to prostate cancer-specific guidelines (74% vs 92%, P = .001). CONCLUSION: Although AI/ANs undergoing cancer operations in Washington receive similar overall best practice surgical cancer care to NHW patients, there remain important, modifiable disparities that may contribute to their lower survival. PMID- 26846179 TI - Preference for practice--recent evidence. PMID- 26846180 TI - Vibrational spectroscopy of metal carbonyls for bio-imaging and -sensing. AB - Transition metal carbonyls exhibit strong CO absorptions in the 2200-1800 cm(-1) region, which is free of interference from other functional groups. This feature has led to their applications in bio-imaging and -sensing, in particular through mid-IR, Raman and more recently, surface-enhanced Raman spectroscopy (SERS). Their use in mid-IR quantitative sensing based on vibrational intensities, and chemical sensing based on frequency shifts and vibrational lifetimes, is reviewed. Their development for Raman sensing following the breakthrough in SERS highlights the potential of coupling metal carbonyls to plasmonic nanostructures as novel optical materials for SERS-based bio-imaging and -sensing. PMID- 26846178 TI - Lessons from computer simulations of ablation of atrial fibrillation. AB - This paper reviews the simulations of catheter ablation in computer models of the atria, from the first attempts to the most recent anatomical models. It describes how postulated substrates of atrial fibrillation can be incorporated into mathematical models, how modelling studies can be designed to test ablation strategies, what their current trade-offs and limitations are, and what clinically relevant lessons can be learnt from these simulations. Drawing a parallel between clinical and modelling studies, six ablation targets are considered: pulmonary vein isolation, linear ablation, ectopic foci, complex fractionated atrial electrogram, rotors and ganglionated plexi. The examples presented for each ablation target illustrate a major advantage of computer models, the ability to identify why a therapy is successful or not in a given atrial fibrillation substrate. The integration of pathophysiological data to create detailed models of arrhythmogenic substrates is expected to solidify the understanding of ablation mechanisms and to provide theoretical arguments supporting substrate-specific ablation strategies. PMID- 26846182 TI - Central Retinal Vein Occlusion Noted 2 Days After Use of Phendimetrazine as an Appetite Suppressant. PMID- 26846181 TI - Significance of the urokinase-type plasminogen activator and its receptor in the progression of focal segmental glomerulosclerosis in clinical and mouse models. AB - BACKGROUND: suPAR biomarker generally considered a pathogenic factor in FSGS. However, studies have been published that dispute this conclusion. The current study was designed to investigate the roles of uPA and suPAR in FSGS in clinical and mouse models. METHODS: Clinical subjects including those with biopsy-proven FSGS and MCD were enrolled. To verify the role of uPA in FSGS, Adriamycin was used to induce FSGS in uPA knockout (uPA(-/-)) and BALB/c (WT) mice. Proteinuria and suPAR, the cleaved/intact forms of the circulating suPAR, and possible proteases involving cleavage of the suPAR were also studied. RESULTS: FSGS clinical cases presented significantly higher serum levels of suPAR and Cr and lower serum levels of uPA. In the mice model, the uPA(-/-) group exhibited faster disease progression and worsening proteinuria than the WT group. In addition, the uPA(-/-) group had higher plasma suPAR levels, glomerular cell apoptosis, and dysregulation of the Th1/Th2 balance. In an analysis of suPAR variants in FSGS, both the intact and cleaved forms of the suPAR were higher in clinical subjects and the mouse model. However, the process of suPAR cleavage was not mediated by enzymatic activities of the uPA, elastase, or cathepsin G. CONCLUSIONS: A deficiency of uPA accelerated the progression of Adriamycin-induced mouse FSGS model. Decrease of serum uPA levels may be an indicator of the progression of FSGS in clinical subjects and animal models. PMID- 26846183 TI - Temozolomide-induced biliary ductopenia: a case report. AB - BACKGROUND: Temozolomide is an alkylating agent used along with concurrent radiation therapy in the treatment of glioblastoma. The primary adverse effect of temozolomide is bone marrow suppression with resulting cytopenias. There have been reported cases of temozolomide-induced hepatotoxicity, including fatal liver failure, associated with reactivation of the hepatitis virus or with concurrent use of other hepatotoxic drugs. In this report, we describe a unique mechanism of temozolomide-induced liver injury with supporting histopathology. CASE PRESENTATION: Our patient, a 58-year-old African american woman with glioblastoma, was treated with concurrent radiation and temozolomide therapy. After 6 weeks of treatment, she developed worsening transaminitis and bilirubinemia with liver biopsy results consistent with drug-induced cholestasis and ductopenia. After cessation of drug treatment, her hyperbilirubinemia progressed with a peak bilirubin of 36.8 mg/dl. A repeat liver biopsy revealed severe biliary ductopenia consistent with vanishing bile duct syndrome. CONCLUSIONS: We present a rare case of a patient with biliary ductopenia as an adverse effect of temozolomide. During radiation and temozolomide therapy, blood counts and liver enzymes should be carefully monitored for the development of cholestatic liver injury. We recommend monitoring with weekly liver function tests and minimizing drugs that are metabolized by the liver during chemoradiation for glioblastoma. PMID- 26846185 TI - Cost-utility analysis of deep brain stimulation surgery plus best medical therapy versus best medical therapy in patients with Parkinson's: Economic evaluation alongside the PD SURG trial. AB - INTRODUCTION: Williams and colleagues reported that DBS surgery for patients with advanced PD improves motor function and quality of life compared to best medical therapy alone at 1 year, but with surgery-related side effects in a minority. This article reports on the economic evaluation alongside this trial. METHODS: Detailed resource use and quality of life over 12 months after randomization was obtained from the trial reported by Williams and colleagues. Outcomes were measured using the EQ-5D and quality-adjusted life years calculated. RESULTS: Year 1 costs for surgery were significantly higher than in best medical therapy, at L19,069 compared to L9,813, a difference of L9,256 (95% confidence interval [CI]: L7,625, L10,887). There was a small, significant gain in utility at 1 year but a statistically insignificant gain of 0.02 quality-adjusted life years (95% CI: -0.015, 0.05) in the surgical arm. The incremental cost per quality-adjusted life year of surgery at 1 year was L468,528. Extrapolation reveals that after 5 years, this ratio is likely to reduce to L45,180, but subsequently rise to L70,537 at 10 years owing to the increased probability of battery replacements (and re-replacements) beyond 5 years. CONCLUSION: In this patient group, DBS is not cost-effective at 1 year. Extrapolation, however, reveals an increasing likelihood of cost-effectiveness up to 5 years and reducing cost-effectiveness between 5 and 10 years. These models are sensitive to assumptions about future costs and quality-adjusted life years gained. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26846186 TI - Stem cell-derived tissue-associated regulatory T cells ameliorate the development of autoimmunity. AB - Pluripotent stem cells (PSCs) have the potential to produce almost all of the cells in the body, including regulatory T cells (Tregs). However, the exact conditions required for the development of antigen (Ag)-specific Tregs from PSCs (i.e., PSC-Tregs) are not well delineated. Ag-specific PSC-Tregs can be tissue/organ-associated and migrate to local inflamed tissues/organs to suppress the autoimmune response after adoptive transfer, thereby avoiding potential overall immunosuppression from non-specific Tregs. In this study, we developed a new approach to generate functional Ag-specific Tregs from induced PSCs (iPSCs), i.e., iPSC-Tregs, which had the ability to generate an Ag-specific immunosuppressive response in a murine model of arthritis. We retrovirally transduced murine iPSCs with a construct containing genes of Ag-specific T cell receptor (TCR) and the transcriptional factor FoxP3. We differentiated the iPSCs into Ag-specific iPSC-Tregs using in vitro or in vivo Notch signaling, and demonstrated that adoptive transfer of such Tregs dramatically suppressed autoimmunity in a well-established Ag-induced arthritis model, including the inflammation, joint destruction, cartilage prostaglandin depletion, osteoclast activity, and Th17 production. Our results indicate that PSCs can be used to develop Ag-specific Tregs, which have a therapeutic potential for Treg-based therapies of autoimmune disorders. PMID- 26846187 TI - Atmospheric concentrations and loadings of organochlorine pesticides and polychlorinated biphenyls in the Canadian Great Lakes Basin (GLB): Spatial and temporal analysis (1992-2012). AB - Long-term air monitoring data for POPs are required to determine the effectiveness of source reduction measures and factors controlling air concentrations. Air samples were collected between 1992 and 2012 at three sites with different geographical characteristics (Burnt Island, Egbert and Point Petre) in the Canadian Great Lakes Basin (GLB) using high-volume samplers and analyzed for organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs). Spatial and temporal trends of gas-phase concentrations of OCPs, selected PCB congeners and ?PCBs (84 congeners) were assessed. Egbert had the highest concentrations of some OCPs due to historical [dichlorodiphenyltrichloroethanes (DDTs), dieldrin, gamma-hexachlorocyclohexane (gamma-HCH)] and current (endosulfan) applications of these pesticides in the surrounding agricultural cropland. This shows that agricultural areas are a source of OCPs to the GLB. High o,p'-/p,p'-DDT ratios were determined and an increasing trend was observed at Point Petre and Burnt Island up to 2004; indicating that the GLB is influenced by dicofol-type DDT sources, which have higher o,p'-/p,p'-DDT ratios than technical DDT. Atmospheric PCB concentrations at Egbert and Point Petre are higher than those measured at Burnt Island, likely due to urban influence and greater populations. Loadings calculations suggest that the atmosphere is a source of alpha-endosulfan and p,p'-DDT to the lakes and the opposite is true for p,p'-DDE. Long-term decreasing trends were observed for both OCPs and PCBs; consistent with control measures implemented in North America. Atmospheric PCB concentrations are decreasing relatively slowly, with halflives in the range of 9 39 years. Chlordane, alpha-endosulfan, beta-endosulfan, dieldrin, and DDT-related substances showed halflives in the range of 7-13 years. alpha-HCH and gamma-HCH were decreasing rapidly in air, with halflives of 5 years. Long-term declining trends of PCBs and OCPs suggest that regulatory efforts to reduce emissions to the GLB environment have been effective, but emissions from primary and secondary sources might limit future declines. PMID- 26846188 TI - Multimodality hard-x-ray imaging of a chromosome with nanoscale spatial resolution. AB - We developed a scanning hard x-ray microscope using a new class of x-ray nano focusing optic called a multilayer Laue lens and imaged a chromosome with nanoscale spatial resolution. The combination of the hard x-ray's superior penetration power, high sensitivity to elemental composition, high spatial resolution and quantitative analysis creates a unique tool with capabilities that other microscopy techniques cannot provide. Using this microscope, we simultaneously obtained absorption-, phase-, and fluorescence-contrast images of Pt-stained human chromosome samples. The high spatial-resolution of the microscope and its multi-modality imaging capabilities enabled us to observe the internal ultra-structures of a thick chromosome without sectioning it. PMID- 26846184 TI - Nonsurgical therapy for hydrocephalus: a comprehensive and critical review. AB - Pharmacological interventions have been tested experimentally and clinically to prevent hydrocephalus and avoid the need for shunting beginning in the 1950s. Clinical trials of varied quality have not demonstrated lasting and convincing protective effects through manipulation of cerebrospinal fluid production, diuresis, blood clot fibrinolysis, or manipulation of fibrosis in the subarachnoid compartment, although there remains some promise in the latter areas. Acetazolamide bolus seems to be useful for predicting shunt response in adults with hydrocephalus. Neuroprotection in the situation of established hydrocephalus has been tested experimentally beginning more recently. Therapies designed to modify blood flow or pulsation, reduce inflammation, reduce oxidative damage, or protect neurons are so far of limited success; more experimental work is needed in these areas. As has been recommended for preclinical studies in stroke and brain trauma, stringent conditions should be met for preclinical studies in hydrocephalus. PMID- 26846189 TI - Ultratrace level determination and quantitative analysis of kidney injury biomarkers in patient samples attained by zinc oxide nanorods. AB - Determining ultratrace amounts of protein biomarkers in patient samples in a straightforward and quantitative manner is extremely important for early disease diagnosis and treatment. Here, we successfully demonstrate the novel use of zinc oxide nanorods (ZnO NRs) in the ultrasensitive and quantitative detection of two acute kidney injury (AKI)-related protein biomarkers, tumor necrosis factor (TNF) alpha and interleukin (IL)-8, directly from patient samples. We first validate the ZnO NRs-based IL-8 results via comparison with those obtained from using a conventional enzyme-linked immunosorbent method in samples from 38 individuals. We further assess the full detection capability of the ZnO NRs-based technique by quantifying TNF-alpha, whose levels in human urine are often below the detection limits of conventional methods. Using the ZnO NR platforms, we determine the TNF alpha concentrations of all 46 patient samples tested, down to the fg per mL level. Subsequently, we screen for TNF-alpha levels in approximately 50 additional samples collected from different patient groups in order to demonstrate a potential use of the ZnO NRs-based assay in assessing cytokine levels useful for further clinical monitoring. Our research efforts demonstrate that ZnO NRs can be straightforwardly employed in the rapid, ultrasensitive, quantitative, and simultaneous detection of multiple AKI-related biomarkers directly in patient urine samples, providing an unparalleled detection capability beyond those of conventional analysis methods. Additional key advantages of the ZnO NRs-based approach include a fast detection speed, low-volume assay condition, multiplexing ability, and easy automation/integration capability to existing fluorescence instrumentation. Therefore, we anticipate that our ZnO NRs based detection method will be highly beneficial for overcoming the frequent challenges in early biomarker development and treatment assessment, pertaining to the facile and ultrasensitive quantification of hard-to-trace biomolecules. PMID- 26846190 TI - Full-thickness periareolar skin resection in mastopexy. PMID- 26846192 TI - Spectroscopic and microcalorimetric studies on the molecular binding of food colorant acid red 27 with deoxyribonucleic acid. AB - Interaction of the food colorant acid red 27 with double stranded DNA was investigated using spectroscopic and calorimetric methods. Absorbance and fluorescence studies suggested an intimate binding interaction between the dye and DNA. The quantum efficiency value testified an effective energy transfer from the DNA base pairs to the dye molecules. Minor groove displacement assay with Hoechst 33258 revealed that the binding occurs in the minor groove of DNA. Circular dichroism studies revealed that acid red 27 induces moderate conformational perturbations in DNA. Results of calorimetric studies suggested that the complexation process was driven largely by positive entropic contribution with a smaller favorable enthalpy contribution. The equilibrium constant of the binding was calculated to be (3.04 +/- 0.09) * 10(4) M(-1) at 298.15 K. Negative heat capacity value along with the enthalpy-entropy compensation phenomenon established the involvement of dominant hydrophobic forces in the binding process. Differential scanning calorimetry studies presented evidence for an increased thermal stability of DNA on binding of acid red 27. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26846191 TI - Electroacupuncture stimulation at CV4 prevents ovariectomy-induced osteoporosis in rats via Wnt-beta-catenin signaling. AB - The present study aimed to investigate the effect of electroacupuncture stimulation at CV4 (also termed Guanyuan) on femoral osteocalcin also termed bone gla protein (BGP), alkaline phosphatase (ALP), bone mineral density (BMD) and biomechanics, as well as the Wnt-beta-catenin signaling pathway in rats with postmenopausal osteoporosis. Female Sprague-Dawley rats (4.5-months old) were randomly divided into sham, Ovx, CV4 and mock groups (n=10/group). With the exception of those in the sham group, the rats were ovariectomized to induce postmenopausal osteoporosis. The rats in the CV4 and mock groups were given electroacupuncture at CV4 and non-acupoint, respectively. The rats in the Ovx model and sham groups underwent identical fixing procedures, but did not undergo electroacupuncture. Following treatment, hematoxylin and eosin staining was used to observe morphological changes in the left femoral trabecular bone, and a three point-bending test was used to analyze femur biomechanics and determine the BMD. In addition, an enzyme-linked immunosorbent assay was used to measure the serum levels of ALP/BGP and reverse transcription-quantitative polymerase chain reaction was used detect the expression levels of Wnt3a, beta-catenin and Runx2. In the present study, it was demonstrated that electroacupuncture at CV4 significantly improved the osteoporotic morphological changes that occurred in the ovariectomized rats, increased serum ALP and BGP levels, enhanced the maximum and fracture loads, increased BMD (P<0.01), and activated the Wnt-beta-catenin signaling pathway. These findings demonstrated that electroacupuncture stimulation at CV4 affected bone formation and promoted bone metabolism in rats with postmenopausal osteoporosis, possibly by activating the Wnt-beta-catenin signaling pathway. PMID- 26846193 TI - Paris Saponins enhance radiosensitivity in a gefitinib-resistant lung adenocarcinoma cell line by inducing apoptosis and G2/M cell cycle phase arrest. AB - Acquired resistance to epidermal growth factor inhibitors has been reported to be associated with cross-resistance to radiation. Paris Saponins (PSs) exert a wide range of pharmacological activities, including cell apoptosis induction, multidrug resistance inhibition, angiogenesis inhibition and tumor cell migration by modulating various signaling pathways. The present study aimed to investigate the radiosensitization effects of PSII, PSVI and PSVII in a gefitinib-resistant PC-9-ZD lung adenocarcinoma cell line, and the possible mechanism underlying their function. A clonogenic assay was performed to determine the effects of PS radiosensitization on the PC-9-ZD cell line. The cell cycle was analyzed by flow cytometry, and cell apoptosis was analyzed with Annexin V/propidium iodide and Hoechst staining. Protein expression levels were detected by western blotting. The results of the present study revealed a significant increase in PC-9-ZD cell line radiosensitivity following treatment with PSs. PSs induced G2/M cell cycle phase arrest and apoptosis of the irradiated PC-9-ZD cells. Notably, the expression levels of B cell lymphoma 2 (Bcl-2) were downregulated, and those of caspase-3, Bcl-2-associated X protein (Bax) and p21/Waf1/Cip1 were upregulated following treatment with PSs. The present results demonstrated that PSs induced radiosensitivity in gefitinib-resistant cells by inducing G2/M phase arrest and by enhancing the apoptotic response via the modulation of caspase-3, Bax, Bcl-2 and p21/Waf1/Cip1 expression. PMID- 26846194 TI - Leaf gas films, underwater photosynthesis and plant species distributions in a flood gradient. AB - Traits for survival during flooding of terrestrial plants include stimulation or inhibition of shoot elongation, aerenchyma formation and efficient gas exchange. Leaf gas films form on superhydrophobic cuticles during submergence and enhance underwater gas exchange. The main hypothesis tested was that the presence of leaf gas films influences the distribution of plant species along a natural flood gradient. We conducted laboratory experiments and field observations on species distributed along a natural flood gradient. We measured presence or absence of leaf gas films and specific leaf area of 95 species. We also measured, gas film retention time during submergence and underwater net photosynthesis and dark respiration of 25 target species. The presence of a leaf gas film was inversely correlated to flood frequency and duration and reached a maximum value of 80% of the species in the rarely flooded locations. This relationship was primarily driven by grasses that all, independently of their field location along the flood gradient, possess gas films when submerged. Although the present study and earlier experiments have shown that leaf gas films enhance gas exchange of submerged plants, the ability of species to form leaf gas films did not show the hypothesized relationship with species composition along the flood gradient. PMID- 26846195 TI - Brain network dysregulation, emotion, and complaints after mild traumatic brain injury. AB - OBJECTIVES: To assess the role of brain networks in emotion regulation and post traumatic complaints in the sub-acute phase after non-complicated mild traumatic brain injury (mTBI). EXPERIMENTAL DESIGN: Fifty-four patients with mTBI (34 with and 20 without complaints) and 20 healthy controls (group-matched for age, sex, education, and handedness) were included. Resting-state fMRI was performed at four weeks post-injury. Static and dynamic functional connectivity were studied within and between the default mode, executive (frontoparietal and bilateral frontal network), and salience network. The hospital anxiety and depression scale (HADS) was used to measure anxiety (HADS-A) and depression (HADS-D). PRINCIPAL OBSERVATIONS: Regarding within-network functional connectivity, none of the selected brain networks were different between groups. Regarding between-network interactions, patients with complaints exhibited lower functional connectivity between the bilateral frontal and salience network compared to patients without complaints. In the total patient group, higher HADS-D scores were related to lower functional connectivity between the bilateral frontal network and both the right frontoparietal and salience network, and to higher connectivity between the right frontoparietal and salience network. Furthermore, whereas higher HADS-D scores were associated with lower connectivity within the parietal midline areas of the bilateral frontal network, higher HADS-A scores were related to lower connectivity within medial prefrontal areas of the bilateral frontal network. CONCLUSIONS: Functional interactions of the executive and salience networks were related to emotion regulation and complaints after mTBI, with a key role for the bilateral frontal network. These findings may have implications for future studies on the effect of psychological interventions. PMID- 26846196 TI - Vasa praevia: improved diagnosis through recognition of risk factors. PMID- 26846197 TI - Suppression of CD51 in pancreatic stellate cells inhibits tumor growth by reducing stroma and altering tumor-stromal interaction in pancreatic cancer. AB - Pancreatic stellate cells (PSCs) enhance the malignant behavior of pancreatic cancer by interacting with cancer cells and producing extracellular matrix (ECM). To date, several stroma-targeted therapies for pancreatic cancer have been attempted, but these therapies are still not in practical use. Integrins expressed in stromal cells are involved in fibrosis of several organs, as well as promoting tumor malignancy. We investigated whether CD51, also known as integrin alphaV, expressed in PSCs was associated with stromal formation of pancreatic cancer and enhancement of tumor malignancy. We also assessed the effects of suppression of CD51 in PSCs on pancreatic cancer. Immunohistochemistry for CD51 in resected pancreatic cancer tissues showed that high expression of CD51 in the tumor stroma was associated with lymph node metastasis (P=0.025), positive pathologic margin (P=0.025), and shorter patient survival times (P=0.043). Lentivirus-mediated short hairpin RNA knockdown of CD51 decreased the proliferation and migration of PSCs. Quantitative real-time polymerase chain reaction showed that expression levels of genes related with ECM and tumor stromal interactions were decreased by CD51 knockdown in PSCs. In a co implantation model of pancreatic cancer cells and PSCs, tumor growth in vivo was inhibited by CD51 knockdown in PSCs (P<0.05). We also found reduced tumor stroma and decreased proliferation of cancer cells in implanted cancer tissues with CD51 silenced PSCs (P<0.05). Our results showed that CD51 expression in pancreatic cancer stroma is associated with enhanced tumor malignancy and that CD51 may be a potential therapeutic target for pancreatic cancer. PMID- 26846198 TI - Comorbid depression, antisocial personality, and substance dependence: Relationship with delay discounting. AB - BACKGROUND: Within the field of addiction, as many as four-fifths of individuals in treatment for substance use disorder have co-existing lifetime psychopathology and as high as two-thirds have current psychopathology. Among substance-dependent individuals, excessive delay discounting is pervasive. Despite evidence of excessive discounting across substance use disorders, few studies have investigated the impact of co-occurring psychopathologies and SUD on delay discounting. METHODS: We compared delay discounting in currently abstaining substance users with (a) SUD (n=166), (b) SUD and managed major depressive disorder (MDD; n=44), (c) SUD and antisocial personality disorder (APD; n=35), (d) SUD and managed MDD and APD (n=22) and (e) no SUD or co-occurring psychopathology (n=60). RESULTS: All groups with SUD discounted future delayed rewards significantly more than healthy controls (p<0.001 in each case, d=0.686, 0.835, 1.098 and 1.650, respective to groups a-d above). Individuals with both APD and SUD and individuals with MDD, APD, and SUD discounted future rewards significantly more than substance users without comorbid psychopathology (p=0.029, d=0.412 and p<0.001, d=0.964, respectively). CONCLUSIONS: Overall, individuals with multiple psychopathologies in addition to substance use have exacerbated deficits in discounting of the future, above and beyond that observed in substance use alone. Increased discounting in combined substance and psychopathology profiles suggest a greater chance of treatment failure and therefore may necessitate individualized treatment using adjunctive interventions to achieve better treatment outcomes. PMID- 26846199 TI - Addendum for Euro Surveill. 2015;20(44). PMID- 26846201 TI - A systematic review and meta-analysis of the association between systemic fluoroquinolones and retinal detachment. AB - PURPOSE: Several pharmacoepidemiologic studies have been carried out evaluating the risk of retinal detachment associated with systemic fluoroquinolones. This meta-analysis aims to investigate such association, in the light of the best scientific evidence available. METHODS: A literature search was conducted to identify relevant studies evaluating the risk for retinal detachment associated with systemic fluoroquinolones. A meta-analysis was performed to pool rate ratios (RRs). Meta-regressions were conducted aiming to evaluate the influence of time interval between fluoroquinolones use and retinal detachment diagnosis or treatment risk estimates. RESULTS: Ten observational studies from seven publications were included. Overall, fluoroquinolones were not associated with an increased risk for retinal detachment [RR 1.47 (95% CI 0.95-2.27): p = 0.09; I(2) = 92.8%]. When the analysis was stratified according to different study designs, the result was statistically significant for retrospective cohort studies [RR 1.87 (95% CI 1.36-2.58); p < 0.001; I(2) = 0.0%] and for past users of fluoroquinolones, based on data from case-control studies [RR 1.07 (95% CI 1.01 1.12); p = 0.01; I(2) = 0.0%]. According to meta-regressions, the risk for retinal detachment did not vary due to different time intervals between fluoroquinolones prescription and retinal detachment occurrence. No statistically significant results were identified among studies evaluating only rhegmatogenous retinal detachments, as well as among studies that evaluated patients not requiring a prior ophthalmologist visit to be included. CONCLUSIONS: In light of the current available evidence, systemic fluoroquinolones do not seem to be associated with retinal detachment. PMID- 26846202 TI - Determinants of tetanus, pneumococcal and influenza vaccination in the elderly: a representative cross-sectional study on knowledge, attitude and practice (KAP). AB - BACKGROUND: Severity and incidence of vaccine-preventable infections with influenza viruses, s. pneumoniae and c. tetani increase with age. Furthermore, vaccine coverage in the elderly is often insufficient. The aim of this study is to identify socio-economic and knowledge-, attitude- and practice- (KAP)-related determinants of vaccination against influenza, pneumococcal disease and tetanus in the older German population. METHODS: We analysed data from a German nationally representative questionnaire-based KAP-survey on infection prevention and hygiene behavior in the elderly (n = 1223). We used logistic regressions to assess impacts of socio-demographic- and KAP-related variables on vaccine uptake in general and on tetanus-, influenza- and pneumococcal vaccination. To generate KAP-scores, we applied factor analyses and analysed scores as predictors of specific vaccinations. RESULTS: A low rated personal health status was associated with a higher uptake of influenza vaccine whereas place of residence within Germany strongly impacted on pneumococcal vaccination. For tetanus and influenza vaccination, the strongest single vaccination predictor was attitude-related, i.e., the perceived importance of the vaccine (OR = 18.1, 95 % CI = 4.5-71.8; OR = 23.0, 95 % CI = 14.9-35.3, respectively). Pneumococcal vaccination was mostly knowledge-associated, i.e., knowing the recommendation predicted uptake (OR = 17.1, 95 % CI = 9.5-30.7). Regarding the generated KAP-scores, the practice-score reflecting vaccine related behavior such as having a vaccination record, was predictive for all vaccines considered. The knowledge-score was associated with influenza (OR = 1.3, 95 % CI = 1.0-1.6) and pneumococcal vaccination (OR = 1.2, 95 % CI = 1.0-1.5). Uniquely for influenza vaccination, the attitude-score was linked to vaccine uptake (OR = 1.1, 95 % CI = 1.0-1.1). CONCLUSIONS: Our results indicate that predictors of vaccination uptake in the elderly strongly depend on vaccine type and that scores of KAP are useful and valid to condense information from numerous individual KAP-variables. While awareness for vaccinations against influenza and tetanus is fairly high already it might have to be increased for vaccinations against pneumocoocal infections. PMID- 26846203 TI - Processing of positive-causal and negative-causal coherence relations in primary school children and adults: a test of the cumulative cognitive complexity approach in German. AB - Establishing local coherence relations is central to text comprehension. Positive causal coherence relations link a cause and its consequence, whereas negative causal coherence relations add a contrastive meaning (negation) to the causal link. According to the cumulative cognitive complexity approach, negative-causal coherence relations are cognitively more complex than positive-causal ones. Therefore, they require greater cognitive effort during text comprehension and are acquired later in language development. The present cross-sectional study tested these predictions for German primary school children from Grades 1 to 4 and adults in reading and listening comprehension. Accuracy data in a semantic verification task support the predictions of the cumulative cognitive complexity approach. Negative-causal coherence relations are cognitively more demanding than positive-causal ones. Moreover, our findings indicate that children's comprehension of negative-causal coherence relations continues to develop throughout the course of primary school. Findings are discussed with respect to the generalizability of the cumulative cognitive complexity approach to German. PMID- 26846200 TI - Viral-mediated fusion of mesenchymal stem cells with cells of the infarcted heart hinders healing via decreased vascularization and immune modulation. AB - Cell fusion can occur between mesenchymal stem cells (MSCs) transplanted to improve cardiac function and cells of the recipient. The therapeutic benefit or detriment of resultant cell hybrids is unknown. Here we augment fusion of transplanted MSCs with recipient cardiac cell types via viral fusogens to determine how cardiac function is impacted. Using a Cre/LoxP-based luciferase reporter system coupled to biophotonic imaging and echocardiography, we found that augmenting fusion with the vesicular stomatitis virus glycoprotein (VSVG) increased the amount of fusion in the recipient mouse heart, but led to diminished cardiac function. Specifically, MSCs transfected with VSVG (MSC-VSVG) had the lowest mean fold increase in fractional area change (FAC) and cardiac output (CO). Although the amount of fusion detected had a strong positive correlation (Pearson) with fractional area change and cardiac output at day 7, this effect was lost by day 28. The decrease in cardiac function seen with MSC VSVG treatment versus MSC alone or sham treatment was associated with decreased MSC retention, altered immune cell responsiveness and reduced vascularization in the heart. This outcome garners consideration in the context of cellular transplantation to damaged tissues, those with viral infection or other microenvironmental conditions that might promote fusion. PMID- 26846204 TI - Overexpression of uncoupling protein 2 inhibits the high glucose-induced apoptosis of human umbilical vein endothelial cells. AB - Ectopic apoptosis of vascular cells plays a critical role in the early stage development of diabetic retinopathy (DR). Uncoupling protein 2 (UCP2) is a mitochondrial modulator which protects against endothelial dysfunction. However, the role which UCP2 plays in endothelial apoptosis and its association with DR was unclear. In the present study, we investigated whether UCP2 functioned as an inhibitor of DR in endothelial cells. Firstly, we noted that in UCP2-knockout mice retinal cell death and damage in vivo was similar to that of db/db diabetic mice. Additionally, UCP2 knockdown induced caspase-3 activation and exaggerated high glucose (HG)-induced apoptosis of human umbilical vein endothelial cells (HUVECs). Conversely, adenovirus-mediated UCP2 overexpression inhibited the apoptosis of HUVECs and HG-induced caspase-3 activation. Furthermore, HG treatment resulted in the opening of the permeability transition pore (PTP) and liberation of cytochrome c from mitochondria to the cytosol in HUVECs. Notably, UCP2 overexpression inhibited these processes. Furthermore, adenovirus-mediated UCP2 overexpression led to a significant increase in intracellular nitric oxide (NO) levels and a decrease in reactive oxygen species (ROS) generation in HUVECs. Collectively, these data suggest that UCP2 plays an anti-apoptotic role in endothelial cells. Thus, we suggest that approaches which augment UCP2 expression in vascular endothelial cells aid in preventing the early stage development and progression of DR. PMID- 26846205 TI - Simvastatin prevents vascular complications in the chronic reactive oxygen species murine model of systemic sclerosis. AB - Aims Systemic sclerosis (SSc) is characterized by vasculopathy and organ fibrosis. Although microvascular alterations are very well characterized, structural and functional abnormalities of large vessels are not well defined. Therefore, we evaluated the effect of simvastatin administration on aortic and small renal arteries thickening, and on myofibroblasts differentiation in a murine model of SSc. Methods and results SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl, 100 MUl) for 6 weeks. Mice (n = 23) were randomized to receive: HOCl (n = 10); HOCl plus simvastatin (40 mg/kg; n = 8); or vehicle (n = 5). Simvastatin administration started 30 min after HOCl injection, and up to week 6. Aortic and small renal arteries intima-media thickness was evaluated by histological analysis. Immunostaining for alpha-smooth muscle actin (SMA), vascular endothelial growth factor receptor 2 (VEGFR2), and CD31 in aortic tissues was performed to evaluate myofibroblast differentiation and endothelial markers.In HOCl-treated mice, intima-media thickening with reduced lumen diameter was observed in the aorta and in small renal arteries and simvastatin administration prevented this increase. Aortic and renal myofibroblasts count, as expressed by alpha-SMA + density, was lower in the group of mice treated with simvastatin compared to HOCl-treated mice. Simvastatin prevented the reduction in VEGFR2 and CD31 expression induced by HOCl. Conclusions The administration of simvastatin regulates collagen deposition in the aortic tissues and in the small renal arteries by modulating myofibroblasts differentiation and vascular markers. Further studies are needed to better address the effect of statins in the macrovascular component of SSc. PMID- 26846208 TI - Clinical management of dyslipidaemia associated with combination antiretroviral therapy in HIV-infected patients. AB - The introduction of potent combination antiretroviral therapy (cART) has had a remarkable impact on the natural history of HIV infection, leading to a dramatic decline in the mortality rate and a considerable increase in the life expectancy of HIV-positive people. However, cART use is frequently associated with several metabolic complications, mostly represented by lipid metabolism alterations, which are reported very frequently among persons treated with antiretroviral agents. In particular, hyperlipidaemia occurs in up to 70%-80% of HIV-positive subjects receiving cART and is mainly associated with specific antiretroviral drugs belonging to three classes of antiretroviral agents: NRTIs, NNRTIs and PIs. The potential long-term consequences of cART-associated dyslipidaemia are not completely understood, but an increased risk of premature coronary heart disease has been reported in HIV-infected patients on cART, so prompt correction of lipid metabolism abnormalities is mandatory in this population. Dietary changes, regular aerobic exercise and switching to a different antiretroviral regimen associated with a more favourable metabolic profile are the first steps in clinical management, but lipid-lowering therapy with fibrates or statins is often required. In this case, the choice of hypolipidaemic drugs should take into account the potential pharmacokinetic interactions with many antiretroviral agents. PMID- 26846206 TI - Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation. AB - Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Here we demonstrate that Arg-II(-/-) mice reveal decreased hepatic steatosis, macrophage infiltration, TNF-alpha and IL-6 as compared to the wild type (WT) littermates fed high fat diet (HFD). A higher AMPK activation (no difference in mTOR signaling), lower levels of lipogenic transcription factor SREBP-1c and activity/expression of lipogenic enzymes were observed in the Arg-II(-/-) mice liver. Moreover, release of TNF-alpha and IL-6 from bone marrow-derived macrophages (BMM) of Arg-II(-/-) mice is decreased as compared to WT-BMM. Conditioned medium from Arg-II(-/-)-BMM exhibits weaker activity to facilitate triglyceride synthesis paralleled with lower expression of SREBP-1c and SCD-1 and higher AMPK activation in hepatocytes as compared to that from WT-BMM. These effects of BMM conditioned medium can be neutralized by neutralizing antibodies against TNF-alpha and IL-6. Thus, Arg-II-expressing macrophages facilitate diet-induced NAFLD through TNF-alpha and IL-6 in obesity. PMID- 26846209 TI - Differences in the pharmacodynamics of ceftaroline against different species of Enterobacteriaceae studied in an in vitro pharmacokinetic model of infection. AB - OBJECTIVES: Dose-ranging experiments were performed to study the pharmacodynamics of ceftaroline against Enterobacteriaceae. METHODS: A range of fT>MIC values (0% 100%) were simulated over 96 h using a single-compartment dilutional in vitro pharmacokinetic model using Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Citrobacter koseri and Serratia marcescens (n = 16). Antibacterial effect was assessed by change in viable count and population profiles by growth on ceftaroline MIC *2, *4 and *8 agar plates. The fT>MIC (%) was related to antibacterial effect using a sigmoid Emax model. RESULTS: The 24 h bacteriostatic effect fT>MIC was 39.7% +/- 15.7% and 43.2% +/- 15.6% for a -1 log drop for all strains. E. coli required lower exposures than K. pneumoniae, i.e. 24 h fT>MIC for a -3 log drop in viable count was 40.0% +/- 9.6% and 84.8% +/- 15.2% for K. pneumoniae. Similarly at 96 h, fT>MIC was >100% for K. pneumoniae (for four of five strains), 27.2%-66.2% for E. coli and 16.2%-86.6% for P. mirabilis. Strain to-strain variation within species in the fT>MIC for static and cidal effect was marked; the 24 h bacteriostatic range was 14.1%-73.4% for P. mirabilis, 34.2% 44.6% for E. coli and 42.2%-62.5% for K. pneumoniae. Changes in ceftaroline population analysis profiles were observed with E. coli, K. pneumoniae and C. koseri, especially at fT>MIC values just below the bacteriostatic effect exposures. CONCLUSIONS: The pharmacodynamics of ceftaroline against the species within the Enterobacteriaceae group are different. K. pneumoniae requires higher drug exposures than E. coli, and P. mirabilis strains are highly variable, which may have important clinical correlates. Translational extrapolations from preclinical observations using E. coli to other Enterobacteriaceae species may not be optimal. PMID- 26846207 TI - Characterization of chromatin accessibility with a transposome hypersensitive sites sequencing (THS-seq) assay. AB - Chromatin accessibility captures in vivo protein-chromosome binding status, and is considered an informative proxy for protein-DNA interactions. DNase I and Tn5 transposase assays require thousands to millions of fresh cells for comprehensive chromatin mapping. Applying Tn5 tagmentation to hundreds of cells results in sparse chromatin maps. We present a transposome hypersensitive sites sequencing assay for highly sensitive characterization of chromatin accessibility. Linear amplification of accessible DNA ends with in vitro transcription, coupled with an engineered Tn5 super-mutant, demonstrates improved sensitivity on limited input materials, and accessibility of small regions near distal enhancers, compared with ATAC-seq. PMID- 26846211 TI - An evaluation of EDTA additions for improving the phytoremediation efficiency of different plants under various cultivation systems. AB - Previous studies have shown that phytoremediation usually requires soil amendments, such as chelates, to mobilize low bioavailability heavy metals for better plant absorption and, consequently, for remediation efficiency. A total dry biomass of 3.39 and 0.0138 kg per plant was produced by a phytoremediator, Eucalyptus globulus, and a nitrogen fixing crop, Cicer arietinum (chickpea), respectively. The accumulation of Pb in E. globulus and chickpea reached 1170.61 and 1.33 mg per plant (700 and 324 mg kg(-1)), respectively, under an ethylene diamine tetraacetic acid (EDTA) treatment, which was a five and sixfold increase over the value in untreated experiments, respectively. EDTA enhanced the phytoremediation efficiency and increased the heavy metal concentration in the soil solution. In pot experiments, approximately 27 % of the initial Pb leached from the spiked soil after EDTA and 25 mm artificial precipitation additions into soil without plants, which was considerably larger than the value under the same conditions without EDTA application (7 %). E. globulus planted in a mixed culture had higher water use efficiency than monocultures of either species in field experiments, and E. globulus intercepted almost all of the artificial precipitation in the pot experiments. This study demonstrates that E. globulus can maximize the potential of EDTA for improving the phytoremediation efficiency and minimizing its negative effects to the environment simultaneously by absorbing the metal-rich leachate, especially in a mixed culture of E. globulus and chickpeas. PMID- 26846210 TI - KPC enzymes in the UK: an analysis of the first 160 cases outside the North-West region. AB - OBJECTIVES: Klebsiella pneumoniae carbapenemases (KPCs) have been increasingly reported in the UK since 2003. We analysed patient and isolate data for KPC positive bacteria confirmed by the national reference laboratory from UK laboratories from August 2003 to August 2014, excluding North-West England, where the epidemiology has previously been studied. METHODS: MICs were determined by BSAC agar dilution. Carbapenem-resistant isolates lacking imipenem/EDTA synergy were tested by PCR for blaKPC. MLST and blaKPC sequencing were performed on a subset of isolates. Plasmid analysis was performed by transformation, PCR-based replicon typing and, in some cases, whole-plasmid sequencing. Patient data provided by the sending laboratories were reviewed. RESULTS: Two hundred and ten isolates with KPC enzymes were submitted from 71 UK laboratories outside North West England, representing 160 patients. All were Enterobacteriaceae, predominantly K. pneumoniae (82%; 173/210), and most (91%; 191/210) were from hospitalized patients. Analysis of 100 isolates identified blaKPC-2 (62%), blaKPC 3 (30%) and blaKPC-4 (8%). Clonal group (CG) 258 was dominant among K. pneumoniae (64%; 54/84), but 21 unrelated STs were also identified. Plasmid analysis identified a diverse range of plasmids representing >11 different replicon types and found in multiple STs and species. Most (34/35) plasmids with IncFIB/FIIK replicons exhibited >99% sequence identity to pKpQIL. CONCLUSIONS: KPC enzymes are increasingly detected in Enterobacteriaceae in the UK, albeit without the major outbreaks seen in North-West England. K. pneumoniae CG258 are the dominant hosts, but plasmid spread plays a major role in KPC dissemination between other K. pneumoniae STs and enterobacterial species. PMID- 26846212 TI - Limitations in dose-response and surrogate species methodologies for risk assessment of Cry toxins on arthropod natural enemies. AB - Dose-response assays and surrogate species are standard methods for risk analysis for environmental chemicals. These assume that individuals within a species have unimodal responses and that a surrogate species can predict responses of other related taxa. We exposed immature individuals of closely related aphidophagous coccinellid predators, Cycloneda sanguinea and Harmonia axyridis, to Cry1Ac and Cry1F toxins through uniform and constant artificial tritrophic exposure through Myzus persicae aphids. Both toxins were detected in coccinellid pupae, with individual and interspecific variation. Uptake was significantly higher in H. axyridis than in C. sanguinea, both in the proportion of individuals and the concentrations per individual. We also observed bimodal uptake of the Cry toxins by H. axyridis, which indicated that some individuals had low bioaccumulation and some had high bioaccumulation. This suggests that standard dose-response assays need to be interpreted with caution and future assays should examine the modality of the responses. In addition, the similarity in the biological effects of the Cry toxins in the two predators was due to different biological exposure mechanisms. The majority of H. axyridis were exposed both internally and in the gut, while C. sanguinea was exposed primarily in the gut. Thus, despite their close phylogenetic relatedness, these species would not be good surrogates for each other and the surrogate species methodology should be tested more rigorously. PMID- 26846213 TI - FOXR2 contributes to cell proliferation and malignancy in human hepatocellular carcinoma. AB - Forkhead box R2 (FOXR2), a member of forkhead box (FOX) family, has been identified as an oncogene in medulloblastoma and breast cancer recently. However, the expression and function of FOXR2 in hepatocellular carcinoma cell (HCC) are still unclear. Here, we report that FOXR2 is frequently upregulated in 25/42 (59.5 %) of HCC specimens compared with neighboring non-cancerous tissues in messenger RNA (mRNA) level and further confirmed by immunohistochemistry analysis in protein level. Cellular function analyses revealed that FOXR2 promoted cell growth and colony formation, whereas knockdown of FOXR2 by RNA inference inhibited cell growth and decreased the growth ability of HCC cells in soft agar. Moreover, we also found FOXR2 overexpression facilitated the development of tumor xenografts in nude mice model. In addition, we validated beta-catenin, Skp2, c Myc, and Gli-1 as the potential downstream effectors of FOXR2 in the regulation of cell proliferation and malignancy by quantitative real-time PCR analysis. Collectively, our data suggest that FOXR2 promotes cell proliferation and malignancy in HCC and could be a novel promising therapeutic target for this disease. PMID- 26846214 TI - Roles of CDKN1A gene polymorphisms (rs1801270 and rs1059234) in the development of cervical neoplasia. AB - The CDKN1A gene product is a p53 downstream effector, which participates in cell differentiation, development process, repair, apoptosis, senescence, migration, and tumorigenesis. The objective of our study was investigated the importance of two polymorphisms in the CDKN1A gene, rs1801270 (31C>A) and rs1059234 (70C>T), for the development of cervical lesions in a Southeastern Brazilian population (283 cases, stratified by lesion severity, and 189 controls). CDKN1A genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and/or DNA sequencing. CDKN1A 31A allele presents a genetic pattern of protection for the development of high-grade cervical lesions (CC vs CA genotype: OR = 0.60; 95 % CI = 0.38-0.95; p = 0.029; CA+AA vs CC genotype: OR = 0.60; 95 % CI = 0.39-0.93; p = 0.021). Allele distributions of the CDKN1A 70C>T polymorphism were also different between the two study groups, with the CDKN1A 70T allele being less prevalent among cases. Moreover, the double heterozygote genotype combination 31CA-70CT decreases the chance of developing high-grade squamous intraepithelial lesion (HSIL) and cancer (OR = 0.55; 95 % CI = 0.32-0.93; p = 0.034) by 50 %, representing a protective factor against the development of more severe cervical lesions. PMID- 26846215 TI - Frequencies of EGFR single nucleotide polymorphisms in non-small cell lung cancer patients and healthy individuals in the Republic of Serbia: a preliminary study. AB - The purpose of this study was to determine the frequencies of EGFR -216G>T, 191C>A, and 181946C>T in Serbian non-small cell lung cancer (NSCLC) patients, as well as to compare it with healthy individuals, in order to assess their potential importance for lung cancer in Serbia. The study involved 56 NSCLC patients and 53 unrelated healthy volunteers, and genotyping was performed on DNA samples obtained from formalin-fixed paraffin-embedded lung tumor tissue and blood, respectively. This was the first time to show genotype frequencies of those single nucleotide polymorphisms for this study group from the territory of the Republic of Serbia. There was very strong evidence of association between age and death due to lung cancer (Pearson chi-square = 43.439, df = 2, p < 0,001), as well as between ever smoking and death due to lung cancer (Pearson chi-square = 31.727, df = 1, p < 0.001). When dominant genetic model (GG vs. GT+TT) was used for -216G>T, we have found significant association (p = 0.012) between -216GG genotype and NSCLC patients within smokers' subgroup. So, carriers of -216GG genotype had higher risk (OR = 4.33, 95 % CI = 1.324-14.179) than noncarriers (GT and TT) for developing non-small cell lung cancer in our patients. PMID- 26846216 TI - Inter-Population Variability of Endosymbiont Densities in the Asian Citrus Psyllid (Diaphorina citri Kuwayama). AB - The Asian citrus psyllid (Diaphorina citri Kuwayama) is an insect pest capable of transmitting Candidatus Liberibacter asiaticus (CLas), the causal agent of citrus greening in North America. D. citri also harbors three endosymbionts, Wolbachia, Candidatus Carsonella ruddii, and Candidatus Profftella armatura, which may influence D. citri physiology and fitness. Although genomic researches on these bacteria have been conducted, much remains unclear regarding their ecology and inter-population variability in D. citri. The present work examined the densities of each endosymbiont in adult D. citri sampled from different populations using quantitative PCR. Under field conditions, the densities of all three endosymbionts positively correlated with each other, and they are associated with D. citri gender and locality. In addition, the infection density of CLas also varied across populations. Although an analysis pooling D. citri from different populations showed that CLas-infected individuals tended to have lower endosymbiont densities compared to uninfected individuals, the difference was not significant when the population was included as a factor in the analysis, suggesting that other population-specific factors may have stronger effects on endosymbiont densities. To determine whether there is a genetic basis to the density differences, endosymbiont densities between aged CLas-negative females of two D. citri populations reared under standardized laboratory conditions were compared. Results suggested that inter-population variability in Wolbachia infection density is associated with the genotypes of the endosymbiont or the host. Findings from this work could facilitate understanding of D. citri bacterial associations that may benefit the development of approaches for managing citrus greening, such as prevention of CLas transmission. PMID- 26846217 TI - Pulsed (13)C2-Acetate Protein-SIP Unveils Epsilonproteobacteria as Dominant Acetate Utilizers in a Sulfate-Reducing Microbial Community Mineralizing Benzene. AB - In a benzene-degrading and sulfate-reducing syntrophic consortium, a clostridium affiliated to the genus Pelotomaculum was previously described to ferment benzene while various sulfate-reducing Deltaproteobacteria and a member of the Epsilonproteobacteria were supposed to utilize acetate and hydrogen as key metabolites derived from benzene fermentation. However, the acetate utilization network within this community was not yet unveiled. In this study, we performed a pulsed (13)C2-acetate protein stable isotope probing (protein-SIP) approach continuously spiking low amounts of acetate (10 MUM per day) in addition to the ongoing mineralization of unlabeled benzene. Metaproteomics revealed high abundances of Clostridiales followed by Syntrophobacterales, Desulfobacterales, Desulfuromonadales, Desulfovibrionales, Archaeoglobales, and Campylobacterales. Pulsed acetate protein-SIP results indicated that members of the Campylobacterales, the Syntrophobacterales, the Archaeoglobales, the Clostridiales, and the Desulfobacterales were linked to acetate utilization in descending abundance. The Campylobacterales revealed the fastest and highest (13)C incorporation. Previous experiments suggested that the activity of the Campylobacterales was not essential for anaerobic benzene degradation in the investigated community. However, these organisms were consistently detected in various hydrocarbon-degrading and sulfate-reducing consortia enriched from the same aquifer. Here, we demonstrate that this member of the Campylobacterales is the dominant acetate utilizer in the benzene-degrading microbial consortium. PMID- 26846218 TI - High Hypnotizability Impairs the Cerebellar Control of Pain. AB - In the general population, transcranial anodal direct current stimulation of the cerebellum (ctDCS) reduces pain intensity and the amplitude of nociceptive laser evoked potentials (LEPs), whereas cathodal ctDCS elicits opposite effects. Since behavioral findings suggest that the cerebellar activity of highly hypnotizable individuals (highs) differs from the general population, we investigated whether hypnotizability-related differences occur in the modulation of pain by ctDCS. Sixteen healthy highs (according to the Stanford Hypnotic Susceptibility Scale, form A) and 16 participants not selected according to hypnotizability (controls) volunteered to undergo laser nociceptive stimulation of the dorsum of the left hand before and after anodal or cathodal ctDCS. LEPs amplitudes and latencies and the subjective pain experience (Numerical Rating Scale) were analyzed. Smaller LEP amplitudes and longer latencies were observed in highs with respect to controls independently of stimulation. After anodal and cathodal cerebellar stimulation, controls reported lower and higher pain than before it, respectively. In contrast, highs did not report significant changes in the perceived pain after both stimulations. They increased significantly their N2/P2 amplitude after anodal ctDCS and did not exhibit any significant change after cathodal tDCS, whereas controls decreased the N1 and N2P2 amplitude and increased their latency after anodal cerebellar stimulation and did the opposite after cathodal ctDCS. In conclusion, the study showed impaired cerebellar pain modulation and suggested altered cerebral cortical representation of pain in subjects with high hypnotizability scores. PMID- 26846220 TI - Situating beyond the social: understanding the role of materiality in Danish nursing education. AB - Situated learning serves as an analytical framework for learning in a community of practice and has been widely used to understand the learning process that is entailed in becoming a nurse. Yet in this paper, the difficulties encountered with the original notion of situated learning once it is applied to contemporary Danish nursing education are introduced. One issue that has arisen is the analytical requirement for an educational program to be a homogeneous, singular, and social phenomenon thereby discounting the varied and different sites and materialities found within nursing education. By using the materiality of the hospital bed as an empirical example of the way materiality also shapes practices, an alternative understanding of situated participation can emerge. This approach allows different sites and materialities to be conceptualized as equally genuine parts of the situated leaning framework. I suggest the notion of multi-configured learning, which captures the heterogeneity and materiality encountered during ethnographic fieldwork at a Danish nursing school. PMID- 26846219 TI - Endocrine dysregulation in women with irritable bowel syndrome according to Rome II criteria. AB - The etiology of the irritable bowel syndrome (IBS) is unexplained: biological, psychological and social factors must be considered. This study examined if differences in HPA-axis activity already exist in those who do not yet fulfill IBS criteria (i.e. "subthreshold IBS"). We also investigated whether there were differences between those who reported clinically relevant (i.e. distressing) IBS symptoms and those who did not. Thirty-six women were subdivided into three groups (IBS group, subthreshold IBS group, control group). Results showed differences in morning cortisol levels (U = 11.58; p < 0.05), with IBS patients showing a lower cortisol response compared to controls. Subthreshold IBS patients were comparable to controls regarding endocrine function. Diurnal cortisol levels did not differ between groups. Group comparisons between distressed subjects and non-distressed subjects regarding cortisol levels did not reach significance. The finding of endocrine abnormalities (at least in a sub-set of patients) is important since these might be associated with deficient pain processing in IBS. PMID- 26846221 TI - E-learning optimization: the relative and combined effects of mental practice and modeling on enhanced podcast-based learning-a randomized controlled trial. AB - Enhanced podcasts increase learning, but evidence is lacking on how they should be designed to optimize their effectiveness. This study assessed the impact two learning instructional design methods (mental practice and modeling), either on their own or in combination, for teaching complex cognitive medical content when incorporated into enhanced podcasts. Sixty-three medical students were randomised to one of four versions of an airway management enhanced podcast: (1) control: narrated presentation; (2) modeling: narration with video demonstration of skills; (3) mental practice: narrated presentation with guided mental practice; (4) combined: modeling and mental practice. One week later, students managed a manikin-based simulated airway crisis. Knowledge acquisition was assessed by baseline and retention multiple-choice quizzes. Two blinded raters assessed all videos obtained from simulated crises to measure the students' skills using a key elements scale, critical error checklist, and the Ottawa global rating scale (GRS). Baseline knowledge was not different between all four groups (p = 0.65). One week later, knowledge retention was significantly higher for (1) both the mental practice and modeling group than the control group (p = 0.01; p = 0.01, respectively) and (2) the combined mental practice and modeling group compared to all other groups (all ps = 0.01). Regarding skills acquisition, the control group significantly under-performed in comparison to all other groups on the key-events scale (all ps <= 0.05), the critical error checklist (all ps <= 0.05), and the Ottawa GRS (all ps <= 0.05). The combination of mental practice and modeling led to greater improvement on the key events checklist (p = 0.01) compared to either strategy alone. However, the combination of the two strategies did not result in any further learning gains on the two other measures of clinical performance (all ps > 0.05). The effectiveness of enhanced podcasts for knowledge retention and clinical skill acquisition is increased with either mental practice or modeling. The combination of mental practice and modeling had synergistic effects on knowledge retention, but conveyed less clear advantages in its application through clinical skills. PMID- 26846222 TI - Mitochondrial Uncoupling Protein 2 (UCP2) Regulates Retinal Ganglion Cell Number and Survival. AB - In the brain, mitochondrial uncoupling protein 2 (UCP2) has emerged as a stress signal associated with neuronal survival. In the retina, UCP2 is expressed primarily by retinal ganglion cells. Here, we investigated the functional relevance of UCP2 in the mouse retina. Increased expression of UCP2 significantly reduced apoptosis during the critical developmental period resulting in elevated numbers of retinal ganglion cells in the adult. Elevated UCP2 levels also protected against excitotoxic cell death induced by intraocular injection of either NMDA or kainic acid. In monolayer cultures of retinal cells, elevated UCP2 levels increased cell survival and rendered the cells independent of the survival promoting effects of the neurotrophic factors BDNF and CNTF. Taken together, these data implicate UCP2 as an important regulator of retinal neuron survival both during development and in adult animals. PMID- 26846223 TI - [Typical atrial flutter: Diagnosis and therapy]. AB - Typical, cavotricuspid-dependent atrial flutter is the most common atrial macroreentry tachycardia. The incidence of atrial flutter (typical and atypical forms) is age-dependent with 5/100,000 in patients less than 50 years and approximately 600/100,000 in subjects > 80 years of age. Concomitant heart failure or pulmonary disease further increases the risk of typical atrial flutter.Patients with atrial flutter may present with symptoms of palpitations, reduced exercise capacity, chest pain, or dyspnea. The risk of thromboembolism is probably similar to atrial fibrillation; therefore, the same antithrombotic prophylaxis is required in atrial flutter patients. Acutely symptomatic cases may be subjected to cardioversion or pharmacologic rate control to relieve symptoms. Catheter ablation of the cavotricuspid isthmus represents the primary choice in long-term therapy, associated with high procedural success (> 97 %) and low complication rates (0.5 %).This article represents the third part of a manuscript series designed to improve professional education in the field of cardiac electrophysiology. Mechanistic and clinical characteristics as well as management of isthmus-dependent atrial flutter are described in detail. Electrophysiological findings and catheter ablation of the arrhythmia are highlighted. PMID- 26846225 TI - Induction of apoptosis, stimulation of cell-cycle arrest and inhibition of angiogenesis make human amnion-derived cells promising sources for cell therapy of cancer. AB - Amniotic membrane (AM), the nearest layer of fetal membranes to the fetus, contains two types of cells with unique characteristics that make them excellent candidates for clinical applications. Amniotic epithelial and mesenchymal cells have low immunogenicity, anti-inflammation, anti-fibrosis and anti-bacterial properties and no ethical issues. Although amniotic cells have stem cell properties and express transcription factors specific for pluripotent stem cells, they are not tumorigenic after transplantation. In the last decade, a new line of research has been initiated with a focus on the anti-proliferative effects of amniotic epithelial and mesenchymal cells on tumor growth. Amnion-derived epithelial and mesenchymal cells inhibit tumor growth and invasion through three pathways: the induction of apoptosis, the stimulation of cell-cycle arrest and the inhibition of angiogenesis. In this review, the various aspects of the anti cancer properties of amnion-derived cells and the underlying mechanisms are discussed with emphasis on the translation of the cell therapy of cancer from experimental into clinical practice. PMID- 26846224 TI - [Manpower requirements for medical doctors in psychiatric departments of community hospitals--bottom-up calculation for the psychiatric department of Donauspital in Vienna]. AB - BACKGROUND: Clinical psychiatry changed dramatically in the past 30 years. Clinical challenges are very different from those in old mental hospitals. Psychotherapy and sociotherapy are effective but very time-consuming parts of treatments of nearly every psychiatric disorder. Planning of staff resources based on the German "Psychiatrie Personalverordnung" does not match with modern quality requirements. As a result, the standards of evidence-based treatment cannot be offered to severely mentally ill inpatients. METHODS: We carried out a buttom-up calculation of medical staffing for the concrete patients considering diagnosis, and length of stay of the psychiatric department of the Danube hospital in Vienna 2013 and 2014. This is an 80 bed unit responsible for an area of 250,000 inhabitants, providing about 1100 admissions each year. RESULTS: The calculated yearly sum of working hours for medical doctors in the particular department was 39,527. When considering a net working-time of 80%, the actual number of medical staff should be at least doubled to allow psychiatric treatment according to current guidelines. CONCLUSIONS: Severely ill psychiatric patients seem to be undertreated because of low staffing of psychiatric departments. PMID- 26846226 TI - Differentiated localizations of phosphorylated focal adhesion kinase in endothelial cells of rat splenic sinus. AB - The splenic sinus endothelium adhering via adherens junctions and tight junctions regulates the passage of blood cells through the splenic cord. Focal adhesion kinase (FAK) regulates the focal adhesion complex in the basal part of endothelial cells and is an integrated component of cell-cell adhesion, depending on its phosphorylation status. The objectives of this study are to assess the localization of FAK phosphorylated at tyrosine residues and the related proteins of integrin beta5, talin, paxillin, p130Cas, vinculin, RhoA, Rac1, Rac2, Cdc42 and VE-cadherin, in the sinus endothelial cells of rat spleen and to examine the roles of FAK in regulating endothelial adhesion and the passage of blood cells. Immunofluorescence microscopy of tissue cryosections revealed that FAK was localized in the entire circumference of sinus endothelial cells and FAK phosphorylated at Try397 residue (pFAKy397) and pFAKy576 were precisely localized in the adherens junctions of the endothelial cells, whereas pFAKy925 was localized in the basal part of the endothelial cells. Paxillin and vinculin were prominently localized in the basal part of the endothelial cells. Integrin beta5, talin and p130Cas were colocalized with FAK in the entire circumference of sinus endothelial cells. RhoA, Rac2 and Cdc42 were localized in the entire circumference of sinus endothelial cells close to FAK, stress fibers and cortical actin filaments. Immunogold electron microscopy revealed that pFAKy397 and pFAKy576 were colocalized with VE-cadherin, RhoA, Rac2 and Cdc42 in the adherens junctions of the endothelial cells. Possible functional roles of FAK in splenic sinus endothelial cells are also discussed. PMID- 26846227 TI - A Systematic Review and Meta-analysis of Neuroimaging in Oppositional Defiant Disorder (ODD) and Conduct Disorder (CD) Taking Attention-Deficit Hyperactivity Disorder (ADHD) Into Account. AB - Oppositional defiant disorder (ODD) and conduct disorder (CD) are common behavioural disorders in childhood and adolescence and are associated with brain abnormalities. This systematic review and meta-analysis investigates structural (sMRI) and functional MRI (fMRI) findings in individuals with ODD/CD with and without attention-deficit hyperactivity disorder (ADHD). Online databases were searched for controlled studies, resulting in 12 sMRI and 17 fMRI studies. In line with current models on ODD/CD, studies were classified in hot and cool executive functioning (EF). Both the meta-analytic and narrative reviews showed evidence of smaller brain structures and lower brain activity in individuals with ODD/CD in mainly hot EF-related areas: bilateral amygdala, bilateral insula, right striatum, left medial/superior frontal gyrus, and left precuneus. Evidence was present in both structural and functional studies, and irrespective of the presence of ADHD comorbidity. There is strong evidence that abnormalities in the amygdala are specific for ODD/CD as compared to ADHD, and correlational studies further support the association between abnormalities in the amygdala and ODD/CD symptoms. Besides the left precuneus, there was no evidence for abnormalities in typical cool EF related structures, such as the cerebellum and dorsolateral prefrontal cortex. Resulting areas are associated with emotion-processing, error monitoring, problem-solving and self-control; areas associated with neurocognitive and behavioural deficits implicated in ODD/CD. Our findings confirm the involvement of hot, and to a smaller extent cool, EF associated brain areas in ODD/CD, and support an integrated model for ODD/CD (e.g. Blair, Development and Psychopathology, 17(3), 865-891, 2005). PMID- 26846228 TI - Is time spent playing video games associated with mental health, cognitive and social skills in young children? AB - BACKGROUND: Video games are one of the favourite leisure activities of children; the influence on child health is usually perceived to be negative. The present study assessed the association between the amount of time spent playing video games and children mental health as well as cognitive and social skills. METHODS: Data were drawn from the School Children Mental Health Europe project conducted in six European Union countries (youth ages 6-11, n = 3195). Child mental health was assessed by parents and teachers using the Strengths and Difficulties Questionnaire and by children themselves with the Dominic Interactive. Child video game usage was reported by the parents. Teachers evaluated academic functioning. Multivariable logistic regressions were used. RESULTS: 20 % of the children played video games more than 5 h per week. Factors associated with time spent playing video games included being a boy, being older, and belonging to a medium size family. Having a less educated, single, inactive, or psychologically distressed mother decreased time spent playing video games. Children living in Western European countries were significantly less likely to have high video game usage (9.66 vs 20.49 %) though this was not homogenous. Once adjusted for child age and gender, number of children, mothers age, marital status, education, employment status, psychological distress, and region, high usage was associated with 1.75 times the odds of high intellectual functioning (95 % CI 1.31-2.33), and 1.88 times the odds of high overall school competence (95 % CI 1.44-2.47). Once controlled for high usage predictors, there were no significant associations with any child self-reported or mother- or teacher-reported mental health problems. High usage was associated with decreases in peer relationship problems [OR 0.41 (0.2-0.86) and in prosocial deficits (0.23 (0.07, 0.81)]. CONCLUSIONS: Playing video games may have positive effects on young children. Understanding the mechanisms through which video game use may stimulate children should be further investigated. PMID- 26846229 TI - Spinal cord herniation following cervical meningioma excision: a rare clinical entity and review of literature. AB - BACKGROUND: Spinal cord herniation following surgery is an extremely uncommon clinical condition with very few reports in published literature. This condition usually occurs as a spontaneous idiopathic phenomenon often in the thoracic spine or following a scenario of post traumatic spinal cord/nerve root injury. Rarely has it been reported following spinal cord tumor surgery. PURPOSE: To document a case of cervical spinal cord herniation as a late onset complication following spinal cord tumor surgery with an atypical presentation of monoparesis. DESIGN: Case report. METHODS: We describe the clinical presentation, operative procedure, post operative outcome and review of literature of this rare clinical condition. RESULTS: A 57-year-old man presented with right upper limb monoparesis due to a spinal cord herniation 6 years after a cervical intradural meningioma excision. The patients underwent surgery to reduce the herniation and duroplasty with subsequent complete resolution of symptoms. CONCLUSIONS: Spinal cord herniation must be considered as differential diagnosis in scenarios of spinal cord tumor excision presenting with late onset neurological deficit. These cases may present as paraparesis, Brown-sequard syndrome and rarely as in our case as monoparesis. PMID- 26846230 TI - Assessment of sensorimotor control in adults with surgical correction for idiopathic scoliosis. AB - PURPOSE: This study aims at verifying if impaired sensorimotor control observed in adolescents and young adults with scoliosis is also present in adult patients who underwent surgery to reduce their spine deformation. METHODS: The study included ten healthy adults and ten adults with idiopathic scoliosis who underwent surgery to reduce their spine deformation. Galvanic vestibular stimulation was delivered to assess sensorimotor control. Vertical forces under each foot and horizontal displacement of the upper body were measured before, during and after stimulation. Balance control was assessed by calculating the root mean square values of kinematic and kinetic variables. RESULTS: The amplitude of the vestibular-evoked postural response was 3.4 % (0.8-6.0 %) and 4.5 % (-0.4 to 9.5 %) of the maximal range of motion. Therefore, spine surgery did not limit the postural response. Patients with idiopathic scoliosis exhibited larger body sway than the healthy controls during and immediately after vestibular stimulation. The maximal normalized lateral displacement of the body was 0.85 and 0.40 cm/m and maximal normalized vertical force was 0.78 vs. 0.39 N/kg, for idiopathic scoliosis and healthy groups, respectively. CONCLUSIONS: This result suggests that dysfunctional sensorimotor integration is still present even in adult idiopathic scoliosis that underwent spine deformation correction. PMID- 26846232 TI - Rescue of newborn ants by older Cataglyphis cursor adult workers. AB - Cataglyphis cursor worker ants are capable of highly sophisticated rescue behaviour in which individuals are able to identify what has trapped a nestmate and to direct their behaviour towards that obstacle. Nonetheless, rescue behaviour is constrained by workers' subcaste: whereas foragers, the oldest workers, are able both to give and to receive the most help, the youngest workers, inactives, neither give nor receive any help whatsoever; nurses give and receive intermediate levels of aid, reflecting their intermediate age. Such differences in rescue behaviour across subcastes suggest that age and experience play a critical role. In this species, as in many others in which a sensitive period for nestmate recognition exists, newly enclosed ants, called callows, are adopted by ants belonging not only to different colonies but also to different species; foreign callows receive nearly the same special care provided to resident newborns. Because callows are younger than inactives, which are incapable of soliciting rescue, we wondered whether entrapped callows would receive such aid. In the present study, we artificially ensnared individual callows from their own colony (homocolonial), from a different colony (heterocolonial), and from a different species (heterospecific), and tested each one with groups of five potential C. cursor rescuers, either all foragers or all nurses. Our results show that all three types of callows are able to elicit rescue behaviour from both foragers and nurses. Nonetheless, nurse rescuers are better able to discriminate between the three types of callow victims than are foragers. PMID- 26846231 TI - Touchscreen assays of learning, response inhibition, and motivation in the marmoset (Callithrix jacchus). AB - Recent developments in precision gene editing have led to the emergence of the marmoset as an experimental subject of considerable interest and translational value. A better understanding of behavioral phenotypes of the common marmoset will inform the extent to which forthcoming transgenic mutants are cognitively intact. Therefore, additional information regarding their learning, inhibitory control, and motivational abilities is needed. The present studies used touchscreen-based repeated acquisition and discrimination reversal tasks to examine basic dimensions of learning and response inhibition. Marmosets were trained daily to respond to one of the two simultaneously presented novel stimuli. Subjects learned to discriminate the two stimuli (acquisition) and, subsequently, with the contingencies switched (reversal). In addition, progressive ratio performance was used to measure the effort expended to obtain a highly palatable reinforcer varying in magnitude and, thereby, provide an index of relative motivational value. Results indicate that rates of both acquisition and reversal of novel discriminations increased across successive sessions, but that rate of reversal learning remained slower than acquisition learning, i.e., more trials were needed for mastery. A positive correlation was observed between progressive ratio break point and reinforcement magnitude. These results closely replicate previous findings with squirrel monkeys, thus providing evidence of similarity in learning processes across nonhuman primate species. Moreover, these data provide key information about the normative phenotype of wild-type marmosets using three relevant behavioral endpoints. PMID- 26846233 TI - A novel organizational model to face the challenge of multimorbid elderly patients in an internal medicine setting: a case study from Parma Hospital, Italy. AB - Continuous increase of elderly patients with multimorbidity and Emergency Department (ED) overcrowding are great challenges for modern medicine. Traditional hospital organizations are often too rigid to solve them without consistently rising healthcare costs. In this paper we present a new organizational model achieved at Internal Medicine and Critical Subacute Care Unit of Parma University Hospital, Italy, a 106-bed internal medicine area organized by intensity of care and specifically dedicated to such patients. The unit is partitioned into smaller wards, each with a specific intensity level of care, including a rapid-turnover ward (mean length of stay <4 days) admitting acutely ill patients from the ED, a subacute care ward for chronic critically ill subjects and a nurse-managed ward for stable patients who have socio-economic trouble preventing discharge. A very-rapid-turnover ("come'n'go") ward has also been instituted to manage sudden ED overflows. Continuity, effectiveness, safety and appropriateness of care are guaranteed by an innovative figure called "flow manager," with skilled clinical experience and managerial attitude, and by elaboration of an early personalized discharge plan anticipating every patient's needs according to lean methodology principles. In 2012-2014, this organizational model, compared with other peer units of the hospital and of other teaching hospitals of the region, showed a better performance, efficacy and effectiveness indexes calculated on Regional Hospital Discharge Records database system, allowing a capacity to face a massive (+22 %) rise in medical admissions from the ED. Further studies are needed to validate this model from a patient outcome point of view. PMID- 26846235 TI - Degradation and detoxification of the triphenylmethane dye malachite green catalyzed by crude manganese peroxidase from Irpex lacteus F17. AB - Malachite green (MG), a recalcitrant, carcinogenic, and mutagenic triphenylmethane dye, was decolorized and detoxified using crude manganese peroxidase (MnP) prepared from the white rot fungus Irpex lacteus F17. In this study, the key factors (pH, temperature, MG, Mn(2+), H2O2, MnP) in these processes were investigated. Under optimal conditions, 96 % of 200 mg L(-1) of MG was decolorized when 66.32 U L(-1) of MnP was added for 1 h. The K m, V max, and k cat values were 109.9 MUmol L(-1), 152.8 MUmol L(-1) min(-1), and 44.5 s(-1), respectively. The decolorization of MG by MnP followed first-order reaction kinetics with a kinetic rate constant of 0.0129 h(-1). UV-vis and UPLC analysis revealed degradation of MG. Furthermore, seven different intermediates formed during the MnP treatment of 0.5 h were identified by LC-TOF-MS. These degradation products were generated via two different routes by either N-demethylation of MG or the oxidative cleavage of the C-C double bond in MG. Based on ecotoxicity analyses performed on bacteria and algae, it was confirmed that MG metabolites produced by the MnP-catalyzed system were appreciably less toxic than the parent compound. These studies indicate the potential use of this enzyme system in the clean-up of aquatic and terrestrial environments. PMID- 26846236 TI - Determination of the distribution and speciation of selenium in an argillaceous sample using chemical extractions and post-extractions analyses: application to the hydrogeological experimental site of Poitiers. AB - To better understand selenium's dynamics in environmental systems, the present study aims to investigate selenium speciation and distribution in black argillaceous sediments, partially fulfilling karstic cavities into the Hydrogeological Experimental Site of Poitiers. These sediments are suspected to be responsible for selenium concentrations exceeding the European Framework Directive's drinking water limit value (10 MUg L(-1)) in some specific wells. A combination of a sequential extractions scheme and single parallel extractions was thus applied on a representative argillaceous sample. Impacts of the extractions on mineral dissolution and organic matter mobilization were followed by quantifying major cations and total organic carbon (TOC) in the aqueous extracts. The nature of the released organic matter was characterized using thermochemolysis coupled with gas chromatography-mass spectrometry (GC-MS). About 10 % of selenium from the black argillaceous studied matrix could be defined as 'easily mobilizable' when the majority (around 70 %) revealed associated with the aliphatic and alkaline-soluble organic matter's fraction (about 20 %). In these fractions, selenium speciation was moreover dominated by oxidized species including a mixture of Se(VI) (20-30 %) and Se(IV) (70-80 %) in the 'easily mobilizable' fraction, while only Se(IV) was detected in alkaline-soluble organic matter fraction. PMID- 26846234 TI - Apneic oxygenation is associated with a reduction in the incidence of hypoxemia during the RSI of patients with intracranial hemorrhage in the emergency department. AB - Critically ill patients undergoing emergent intubation are at risk of oxygen desaturation during the management of their airway. Patients with intracranial hemorrhage (ICH) are particularly susceptible to the detrimental effects of hypoxemia. Apneic oxygenation (AP OX) may be able to reduce the occurrence of oxygen desaturation during the emergent intubation of these patients. We sought to assess the effect AP OX on oxygen desaturation during the rapid sequence intubation (RSI) of patients with ICH in the emergency department (ED). We prospectively collected data on all patients intubated in an urban academic ED over the 2-year period from July 1, 2013 to June 30, 2015. Following each intubation, the operator completed a standardized continuous quality improvement (CQI) data form, which included information on patient, operator and intubation characteristics. Operators recorded data on the use of AP OX, the oxygen flow rate used for AP OX, and the starting and lowest saturations during intubation. Adult patients with ICH who underwent RSI by emergency medicine (EM) residents were included in the analyses. The primary outcome variable was any oxygen saturation <90 % during the intubation. We performed a backward stepwise multivariate logistic regression analysis to identify variables associated with oxygen desaturation. The primary independent variable of interest was the use of AP OX during the intubation. Inclusion criteria for the study was met by 127 patients. AP OX was used in 72 patients (AP OX group) and was not used in 55 patients (NO AP OX group). The incidence of desaturation was 5/72 (7 %) in the AP OX group and was 16/55 (29 %) in the NO AP OX group. In the multivariate logistic regression analysis the use of AP OX was associated with a reduced odds of desaturation (aOR 0.13; 95 % CI 0.03-0.53). Patients with ICH who received AP OX during RSI in the ED were seven times less likely to have an oxygen saturation of <90 % during the intubation compared to patients who did not receive AP OX. AP OX is a simple intervention that may minimize the risk of oxygen desaturation during the RSI of patients with ICH. PMID- 26846237 TI - Seasonal variability of mercury concentration in soils, buds and leaves of Acer platanoides and Tilia platyphyllos in central Poland. AB - In this paper, we present the results of mercury concentration in soils, buds and leaves of maple (Acer platanoides-Ap) and linden (Tilia platyphyllos-Tp) collected in four periods of the growing season of trees, i.e. in April (IV), June (VI), August (VIII) and November (IX) in 2013, from the area of Poznan city (Poland). The highest average concentration of mercury for 88 samples was determined in soils and it equaled 65.8 +/- 41.7 ng g(-1) (range 14.5-238.9 ng g( 1)); lower average concentration was found in Ap samples (n = 66): 55.4 +/- 18.1 ng g(-1) (range 26.5-106.9 ng g(-1)); in Tp samples 50.4 +/- 15.8 ng g(-1) (range 23.1-88.7 ng g(-1)) and in 22 samples of Tp buds 40.8 +/- 22.7 ng g(-1) (range 12.4-98.7 ng g(-1)) and Ap buds 28.2 +/- 13.6 ng g(-1) (range 8.0-59.5 ng g(-1)). Based on the obtained results, it was observed that the highest concentration of mercury in soils occurred in the centre of Poznan city (95.5 +/- 39.1 ng g(-1)), and it was two times higher than the concentration of mercury in other parts of the city. Similar dependencies were not observed for the leaf samples of Ap and Tp. It was found that mercury concentrations in the soil and leaves of maple and linden were different depending on the period of the growing season (April to November). Mercury content in the examined samples was higher in the first two research periods (April IV, June VI), and then, in the following periods, the accumulation of mercury decreased both in soil and leaf samples of the two tree species. There was no correlation found between mercury concentration in leaves and mercury concentration in soils during the four research periods (April November). When considering the transfer coefficient, it was observed that the main source of mercury in leaves is the mercury coming from the atmosphere. PMID- 26846238 TI - The applied indicators of water quality may underestimate the risk of chemical exposure to human population in reservoirs utilized for human supply-Southern Brazil. AB - The knowledge concerning associations between chronic chemical exposure and many disorders with complex etiology involving gene-environment interactions is increasing, and new methods must be developed to improve water quality monitoring. The complexity of chemical mixtures in polluted aquatic environments makes the evaluation of toxic potential in those sites difficult, but the use of biomarkers and bioindicators has been recognized as a reliable tool to assess risk of exposure to biota and also the human population. In order to evaluate the use of fish and biomarkers to assess toxic potential and bioavailability of chemicals in human-related hydric resources, an in situ experiment was accomplished in two water reservoirs designated for human supply, which were previously evaluated by the local environmental regulatory agency through a set of physical, chemical, and classical biological parameters. Molecular, biochemical, and morphological biomarkers were performed in caged Oreochromis niloticus kept for 6 months in the studied reservoirs to assess potentially useful biomarkers to evaluate the quality of water for human supply. Chemical analysis of toxic metals in liver and muscle and polycyclic aromatic hydrocarbons (PAHs) in bile was considered to assess the bioavailability of pollutants and highlight human activity impact. The reservoir previously classified by a governmental agency as less impacted presented more risk of exposure to biota. These results were supported by chemical analysis, vitellogenin expression, histopathological findings (gonads, liver, and gills), as well as indicators of neurotoxic effects and oxidative stress in liver. The inclusion of some biomarkers as parameters in regulatory monitoring programs in reservoirs designated for human supply is strongly suggested to evaluate the risks of exposure to the human population. Thus, a revision of the traditional biological and physicochemical analysis utilized to establish the conditions of water quality is necessary. PMID- 26846239 TI - Spatial-temporal dynamics and sources of total Hg in a hydroelectric reservoir in the Western Amazon, Brazil. AB - Damming rivers to construct hydroelectric reservoirs results in a series of impacts on the biogeochemical Hg cycle. For example, modifying the hydrodynamics of a natural watercourse can result in the suspension and transport of Hg deposits in the water column, which represents an exposure risk for biota. The objective of this study was to evaluate the influences of seasonality on the dispersion of total Hg in the Hydroelectric Power Plant (HPP)-Samuel Reservoir (Porto Velho/Brazil). Sampling campaigns were performed during the three following hydrological periods characteristic of the region: low (Oct/2011), ebbing (May/2012), and high (Feb/2013) water. Sediment profiles, suspended particulate matter (SPM), and aquatic macrophytes (Eicchornia crassipes and Oryza spp.) were collected, and their Hg concentrations and isotopic and elemental C and N signatures were determined. The drainage basin significantly influenced the SPM compositions during all the periods, with a small autochthonous influence from the reservoir during the low water. The highest SPM Hg concentrations inside the reservoir were observed during the high water period, suggesting that the hydrodynamics of this environment favor the suspension of fine SPM, which has a higher Hg adsorption capacity. The Hg concentrations in the sediment profiles were ten times lower than those in the SPM, indicating that large particles with low Hg concentrations were deposited to form the bottom sediment. Hg concentrations were higher in aquatic macrophyte roots than in their leaves and appeared to contribute to the formation of SPM during the low water period. In this environment, Hg transport mainly occurs in SPM from the Jamari River drainage basin, which is the primary source of Hg in this environment. PMID- 26846240 TI - Biomarkers of oxidative stress and metal accumulation in marsh frog (Pelophylax ridibundus). AB - To understand the effect of metals on the marsh frog Pelophylax ridibundus and the possible environment-induced changes in oxidative stress enzymes, we determined the concentrations of 18 metals: Al, As, Ba, Ca, Cd, Co, Cr, Cu, Fe, Ga, Hg, In, Li, Mn, Ni, Pb, Sr, and Zn, in the tissues (liver, skin, and muscle) and water samples collected from different locations in Serbia. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione reductase (GR), glutathione S-transferase (GST), acetylcholinesterase (AChE), and changes in concentrations of reduced glutathione (GSH) and sulfhydryl groups (SH) were analyzed in the tissues of the sampled frogs. The concentrations of Al, Cd, Co, Cr, Cu, Fe, Ga, Hg, and Ni were highest in the liver, whereas those of Ba, Ca, Li, Mn, Pb, Sr, and Zn were highest in the skin. Hg correlated positively with liver SOD (in frogs from Danube-Tisza-Danube Canal (DTD)), muscle CAT (DTD), and muscle GST Ponjavica River (PO); Pb demonstrated a strong positive correlation with liver GR in frogs from Mt. Fruska Gora (FG); Cd only exhibited a positive correlation with AChE in the skin of frogs from DTD. In the skin, Zn correlated positively with AChE (DTD), SH groups (PO), and CAT (FG), and negatively with CAT, GST, and SH in the liver of frogs from DTD. Examination of these oxidative stress biomarkers, together with analysis of metal accumulation in the liver and skin of marsh frogs, provides a powerful tool for the assessment of metal pollution. PMID- 26846241 TI - Changes in speciation and leaching behaviors of heavy metals in dredged sediment solidified/stabilized with various materials. AB - Solidification/stabilization (S/S) of sediments is frequently used to treat contaminants in dredged sediments. In this study, sediment collected from the Pearl River Delta (China) was solidified/stabilized with three different kinds of functional materials: cement, lime and bentonite. Lime primarily acted via induced increases in pH, while cements stabilization occurred through their silicate-based systems and the main function of bentonite was adsorption. The speciation and leaching behaviors of specific heavy metals before and after S/S were analyzed and the results showed that the residual speciation of Cd, Cr, Ni, Pb and Zn increased in all treatments except for Cu, as the exchangeable speciation, carbonate-bound speciation and Fe-Mn-oxide-bound speciation of Cu (all of which could be stabilized) were less than 2 % of the total amount. Pb leaching only decreased when pH increased, while the mobility of Cr and Ni only decreased in response to the silicate-based systems. The leached portion of the Fe-Mn-oxide-bound speciation followed the order Zn > Cu > Ni/Cd > Pb > Cr. The leached portion of organic-matter-bound species was less than 4 % for Cd, Cr, Ni and Pb, but 35.1 % and 20.6 % for Cu and Zn, respectively. PMID- 26846242 TI - Enhanced photochemical decomposition of environmentally persistent perfluorooctanoate by coexisting ferric ion and oxalate. AB - Perfluorooctanoic acid (PFOA), an environmentally persistent pollutant, was found to be quickly decomposed under 254 nm UV irradiation in the presence of ferric ion and oxalic acid. To understand the PFOA decomposition mechanism by this process, the effects of reaction atmosphere and concentrations of ferric ions and oxalic acids on PFOA decomposition were investigated, as well as decomposition intermediates. PFOA mainly decomposes via two pathways: (i) photochemical oxidation via Fe(III)-PFOA complexes and (ii) one-electron reduction caused by carboxylate anion radical (CO2 (*-)), which was generated by photolysis of ferrioxalate complexes. Under excess oxalic acid, PFOA decomposition was accelerated, and its corresponding half-life was shortened from 114 to 34 min as ferric concentration increased from 7 to 80 MUM. Besides fluoride ions, six shorter chain perfluorinated carboxylic acids (PFCAs) bearing C2-C7 were identified as main intermediates. The presence of O2 promoted the redox recycling of Fe(3+)/Fe(2+) and thus avoided the exhaustion of the Fe(III). PMID- 26846243 TI - Uptake and toxicity of nano-ZnO in the plant-feeding nematode, Xiphinema vuittenezi: the role of dissolved zinc and nanoparticle-specific effects. AB - Nanoparticulate ZnO is one of the most commonly applied nanomaterials. As ZnO is more soluble than many other oxide nanoparticles, its toxicity beyond the nanoparticle-specific effects can be attributed to the dissolved ionic zinc. The investigation of uptake and toxicity of nano-ZnO in the plant-feeding nematode, Xiphinema vuittenezi, which was used in previous studies as a biological model organism, was aimed. The establishment of the role of dissolved zinc and nanoparticle-specific effects in the toxicity was also the objective of our study. Zn uptake was found to be significantly higher for bulk and nano-ZnO than for ZnSO4 solution; however, treatments caused loss of potassium in the worms in a dissolved-zinc-dependent manner. The toxicity was the lowest for bulk ZnO, and it was very similar for nano-ZnO and ZnSO4 solution. Accordingly, the toxicity of ZnO nanoparticles is a combination of dissolved-zinc-caused toxicity and nanoparticle-specific effects. PMID- 26846244 TI - Sorption and degradation of selected organic UV filters (BM-DBM, 4-MBC, and OD PABA) in laboratory water-sediment systems. AB - Organic UV filters that have been widely used in sunscreens and other personal care products have drawn much public concern because of their widespread contamination in the environment and their potential ecological risks to ecosystems. We selected three UV filters with high frequency of detection in the environment, namely butyl methoxy dibenzoylmethane (BM-DBM), ethylhexyl dimethyl p-aminobenzoate (OD-PABA), and 4-methylbenzylidene camphor (4-MBC), to investigate the sorption and degradation behaviors of these compounds in lab scale water-sediment systems set up with natural water and sediment samples collected from different rivers and lakes (i.e., Yangtze River, Qinhuai River, Xuanwu Lake, and Mochou Lake) in Nanjing, East China. The sorption isotherms of these UV filters were well described by the Freundlich equation (C s = K f * C w (n) ). The sorption of three UV filters in four sediments was all linear or close to it, with n values between 0.92 and 1.13. A moderate to strong sorption affinity was observed for these compounds, and the sorption appears to be irreversible. For the combined sorption and degradation studies, sorption was found to be a primary mechanism for the disappearance of these UV filters from the water phase, and biotransformation appears to be the predominant factor for the degradation of the target compounds in the water-sediment systems. All three UV filters were found to be slightly resistant to the microbes in these systems, with DT50total and DT90total values-the disappearance time (DT) describes the time in which the initial total mass of the UV filters in the whole system is reduced by 50 and 90 %-ranging between 18 and 31 days and 68 and 101 days, respectively. PMID- 26846245 TI - Short-term effects of atmospheric particulate matter on myocardial infarction: a cumulative meta-analysis. AB - Atmospheric particulate matter (PM) is hypothesized to increase the risk of myocardial infarction (MI). However, the epidemiological evidence is inconsistent. We identified 33 studies with more than 4 million MI patients and applied meta-analysis and meta-regression to assess the available evidence. Twenty-five studies presented the effects of the PM level on hospitalization for MI patients, while eight studies showed the effects on mortality. An increase in PM10 was associated with hospitalization and mortality in myocardial infarction patients (RR per 10 MUg/m(3) = 1.011, 95% CI 1.006-1.016; RR per 10 MUg/m(3) = 1.008, 95 % CI 1.004-1.012, respectively); PM2.5 also increased the risk of hospitalization and mortality in MI patients (RR per 10 MUg/m(3) = 1.024, 95% CI 1.007-1.041 for hospitalization and RR per 10 MUg/m(3) = 1.012, 95% CI 1.010 1.015 for mortality). The results of the cumulative meta-analysis indicated that PM10 and PM2.5 were associated with myocardial infarction with the addition of new studies each year. In conclusion, short-term exposure to high PM10 and PM2.5 levels revealed to increase risk of hospitalization and mortality for myocardial infarction. Policy support of pollution control and individual protection was strongly recommended. PMID- 26846246 TI - Microglial cells (BV-2) internalize titanium dioxide (TiO2) nanoparticles: toxicity and cellular responses. AB - Because of their whitening and photocatalytic effects, titanium dioxide nanoparticles (TiO2-NPs) are widely used in daily life. These NPs can be found in paints, plastics, papers, sunscreens, foods, medicines (pills), toothpastes, and cosmetics. However, the biological effect of TiO2-NPs on the human body, especially on the central nervous system, is still unclear. Many studies have demonstrated that the brain is one of the target organs in acute or chronic TiO2 NPs toxicity. The present study aimed to investigate the effect of TiO2-NPs at different concentrations (0.1 to 200 MUg/mL) on murine microglial cells (BV-2) to assess their activity on cell growth and viability, as well as their neurotoxicity. Different parameters were measured: cell viability, cell proliferation and DNA content (SubG1 peak), mitochondrial depolarization, overproduction of reactive oxygen species (especially superoxide anions), and ultrastructural changes. Results showed that TiO2-NPs induced some cytotoxic effects with a slight inhibition of cell growth. Thus, at high concentrations, TiO2-NPs were not only able to inhibit cell adhesion but also enhanced cytoplasmic membrane permeability to propidium iodide associated with a loss of mitochondrial transmembrane potential and an overproduction of superoxide anions. No induction of apoptosis based on the presence of a SubG1 peak was detected. The microscopic observations also indicated that small groups of nanosized particles and micron-sized aggregates were engulfed by the BV-2 cells and sequestered as intracytoplasmic aggregates after 24-h exposure to TiO2-NPs. Altogether, our data show that the accumulation TiO2-NPs in microglial BV-2 cells favors mitochondrial dysfunctions and oxidative stress. PMID- 26846247 TI - Optimization of a combined electrocoagulation-electroflotation reactor. AB - This work studies the efficiency of an electroflotation process for the separation of the solids produced during the electrocoagulation treatment of three different types of wastewater: kaolin suspension, coloured organic solution and oil-in-water emulsion. Additionally, a combined electrocoagulation electroflotation reactor is designed and optimized taking into account the effect of current density, residence time, pollutant concentration and the ratio floated/settled solids. To do this, an experimental design with response surface methodology (RSM) has been used. Results show that electroflotation is a good alternative to the removal of oil microdrops and dyes, but it is not recommended for the separation of solids formed during electrocoagulation of colloid suspensions due to its high density. It has been found that the use of aluminium leads to better results than the use of iron in the treatment of oil-in-water emulsions and coloured solutions. In these cases, the use of a combined electrocoagulation-electroflotation reactor is recommended and the effect of the main inputs has been studied. PMID- 26846249 TI - Erratum to: Accumulation pattern and distribution of polycyclic aromatic hydrocarbons (PAHs) in liver tissues of seven species of birds from Ahmedabad, India, during 2005-2007. PMID- 26846250 TI - Thin Nanoporous Metal-Insulator-Metal Membranes. AB - Insulating nanoporous materials are promising platforms for soft-ionizing membranes; however, improvement in fabrication processes and the quality and high breakdown resistance of the thin insulator layers are needed for high integration and performance. Here, scalable fabrication of highly porous, thin, silicon dioxide membranes with controlled thickness is demonstrated using plasma-enhanced chemical-vapor-deposition. The fabricated membranes exhibit good insulating properties with a breakdown voltage of 1 * 10(7) V/cm. Our calculations suggest that the average electric field inside a nanopore of the membranes can be as high as 1 * 10(6) V/cm; sufficient for ionization of wide range of molecules. These metal-insulator-metal nanoporous arrays are promising for applications such soft ionizing membranes for mass spectroscopy. PMID- 26846248 TI - Treatment of real industrial wastewater using the combined approach of advanced oxidation followed by aerobic oxidation. AB - Fenton oxidation and ultrasound-based pretreatment have been applied to improve the treatment of real industrial wastewater based on the use of biological oxidation. The effect of operating parameters such as Fe(2+) loading, contact time, initial pH, and hydrogen peroxide loading on the extent of chemical oxygen demand (COD) reduction and change in biochemical oxygen demand (BOD5)/COD ratio has been investigated. The optimum operating conditions established for the pretreatment were initial pH of 3.0, Fe(2+) loading of 2.0, and 2.5 g L(-1) for the US/Fenton/stirring and Fenton approach, respectively, and temperature of 25 degrees C with initial H2O2 loading of 1.5 g L(-1). The use of pretreatment resulted in a significant increase in the BOD5/COD ratio confirming the production of easily digestible intermediates. The effect of the type of sludge in the aerobic biodegradation was also investigated based on the use of primary activated sludge (PAS), modified activated sludge (MAS), and activated sludge (AS). Enhanced removal of the pollutants as well as higher biomass yield was observed for MAS as compared to PAS and AS. The use of US/Fenton/stirring pretreatment under the optimized conditions followed by biological oxidation using MAS resulted in maximum COD removal at 97.9 %. The required hydraulic retention time for the combined oxidation system was also significantly lower as compared to only biological oxidation operation. Kinetic studies revealed that the reduction in the COD followed a first-order kinetic model for advanced oxidation and pseudo first-order model for biodegradation. The study clearly established the utility of the combined technology for the effective treatment of real industrial wastewater. PMID- 26846251 TI - Computerized Automated Quantification of Subcutaneous and Visceral Adipose Tissue From Computed Tomography Scans: Development and Validation Study. AB - BACKGROUND: Computed tomography (CT) is often viewed as one of the most accurate methods for measuring visceral adipose tissue (VAT). However, measuring VAT and subcutaneous adipose tissue (SAT) from CT is a time-consuming and tedious process. Thus, evaluating patients' obesity levels during clinical trials using CT scans is both cumbersome and limiting. OBJECTIVE: To describe an image processing-based and automated method for measuring adipose tissue in the entire abdominal region. METHODS: The method detects SAT and VAT levels using a separation mask based on muscles of the human body. The separation mask is the region that minimizes the unnecessary space between a closed path and muscle area. In addition, a correction mask, based on bones, corrects the error in VAT. RESULTS: To validate the method, the volume of total adipose tissue (TAT), SAT, and VAT were measured for a total of 100 CTs using the automated method, and the results compared with those from manual measurements obtained by 2 experts. Dice's similarity coefficients (DSCs) between the first manual measurement and the automated result for TAT, SAT, and VAT are 0.99, 0.98, and 0.97, respectively. The DSCs between the second manual measurement and the automated result for TAT, SAT, and VAT are 0.98, 0.98, and 0.97, respectively. Moreover, intraclass correlation coefficients (ICCs) between the automated method and the results of the manual measurements indicate high reliability as the ICCs for the items are all .99 (P<.001). CONCLUSIONS: The results described in this paper confirm the accuracy and reliability of the proposed method. The method is expected to be both convenient and useful in the clinical evaluation and study of obesity in patients who require SAT and VAT measurements. PMID- 26846252 TI - Retirement and perceived social inferiority strongly link with health inequalities in older age: decomposition of a concentration index of poor health based on Polish cross-sectional data. AB - BACKGROUND: Identifying mechanisms that generate and sustain health inequalities is a prerequisite for developing effective policy response, but little is known about factors contributing to health inequalities in older populations in post transitional European countries such as Poland. Demographic aging of all populations requires new and deeper insights. METHODS: Data came from the Polish edition of the cross-sectional European Social Survey, Wave 6 (2012). Logistic regression was applied to identify socioeconomic factors relevant to self assessed health in a population aged 45 or over. Decomposition of a concentration index provided information about the distribution of health-relevant demographics and social characteristics along a socioeconomic continuum, and their contributions to observed health inequalities. RESULTS: Overall, 17.4 % of respondents aged 45 or over assessed their health as poor or very poor. Predictors of poor health included income insufficiency, disability or retirement, retirement, low social activity, and social position. A steep socioeconomic gradient in self-assessed health in Polish population was found. The primary contributor to the observed health inequality (as summarized by concentration index) was income, followed by labor market situation, particularly retirement. Self-assessed place in society contributed to overall inequality, scoring similarly to social activity. Contributions from age and education were moderate but non-significant, gender was negligible, and chronological aging explained neither poor health nor socioeconomic health inequalities. CONCLUSIONS: Although elderly people represent a particularly vulnerable group, their disadvantages are associated with social rather than natural causes. Policies addressing health inequalities in aging populations must provide systemic opportunities for maintaining good health. Transitioning to retirement is a critical entry point for policy action that stimulates social engagement and maintains self-esteem of older people. PMID- 26846253 TI - Does touch massage facilitate recovery after stroke? A study protocol of a randomized controlled trial. AB - BACKGROUND: Despite high quality stroke care, decreased sensorimotor function, anxiety and pain often remain one year after stroke which can lead to impaired health and dependence, as well as higher healthcare costs. Touch massage (TM) has been proven to decrease anxiety and pain, and improve quality of health in other conditions of reduced health, where reduced anxiety seems to be the most pronounced benefit. Thus there are reasons to believe that TM may also reduce anxiety and pain, and improve quality of life after stroke. Further, several studies indicate that somatosensory stimulation can increase sensorimotor function, and it seems feasible to believe that TM could increase independence after stroke. In this study we will evaluate effects of TM after stroke compared to sham treatment. METHODS: This is a prospective randomized open-labelled control trial with blinded evaluation (PROBE-design). Fifty patients with stroke admitted to stroke units will be randomized (1:1) to either a TM intervention or a non-active transcutaneous electrical nerve stimulation (non-TENS) control group. Ten sessions of 30 min treatments (TM or control) will be administered during two weeks. Assessment of status according to the International Classification of Functioning, Disability and Health (ICF), including body function, activity, and participation. Assessment of body function will include anxiety, pain, and stress response (heart rate variability and salivary cortisol), where anxiety is the primary outcome. Activity will be assessed by means of sensorimotor function and disability, and participation by means of health-related quality of life. Assessments will be made at baseline, after one week of treatment, after two weeks of treatment, and finally a follow-up after two months. The trial has been approved by the Regional Ethical Review Board. DISCUSSION: TM seems to decrease anxiety and pain, increase health-related quality of life, and improve sensorimotor functions after stroke, but the field is largely unexplored. Considering the documented pleasant effects of massage in general, absence of reported adverse effects, and potential effects in relation to stroke, it is essential to evaluate effects of TM during the sub-acute phase after stroke. The results of this project will hopefully provide important knowledge for evidence-based care. TRIAL REGISTRATION: ClinicalTrials.gov: NTC01883947. PMID- 26846254 TI - Analysis of Flame Retardancy in Polymer Blends by Synchrotron X-ray K-edge Tomography and Interferometric Phase Contrast Movies. AB - Underwriters Laboratories 94 test bars have been imaged with X-ray K-edge tomography between 12 and 32 keV to assess the bromine and antimony concentration gradient across char layers of partially burnt samples. Phase contrast tomography on partially burnt samples showed gas bubbles and dark-field scattering ascribed to residual blend inhomogeneity. In addition, single-shot grating interferometry was used to record X-ray movies of test samples during heating (IR and flame) intended to mimic the UL 94 plastics flammability test. The UL 94 test bars were formulated with varying concentrations of a brominated flame retardant, Saytex 8010, and a synergist, Sb2O3, blended into high-impact polystyrene (HIPS). Depending on the sample composition, samples will pass or fail the UL 94 plastics flammability test. Tomography and interferometry imaging show differences that correlate with UL 94 performance. Key features such as char layer, gas bubble formation, microcracks, and dissolution of the flame retardant in the char layer regions are used in understanding the efficiency of the flame retardant and synergist. The samples that pass the UL 94 test have a thick, highly visible char layer as well as an interior rich in gas bubbles. Growth of gas bubbles from flame-retardant thermal decomposition is noted in the X-ray phase contrast movies. Also noteworthy is an absence of bubbles near the burning surface of the polymer; dark-field images after burning suggest a microcrack structure between interior bubbles and the surface. The accepted mechanism for flame retardant activity includes free radical quenching in the flame by bromine and antimony species. The imaging supports this as well as provides a fast inspection of other parameters, such as viscosity and surface tension. PMID- 26846255 TI - Population structure and associated phenotypes of Salmonella enterica serovars Derby and Mbandaka overlap with host range. AB - BACKGROUND: The Salmonella enterica serovar Derby is frequently isolated from pigs and turkeys whereas serovar Mbandaka is frequently isolated from cattle, chickens and animal feed in the UK. Through comparative genomics, phenomics and mutant construction we previously suggested possible mechanistic reasons why these serovars demonstrate apparently distinct host ranges. Here, we investigate the genetic and phenotypic diversity of these two serovars in the UK. We produce a phylogenetic reconstruction and perform several biochemical assays on isolates of S. Derby and S. Mbandaka acquired from sites across the UK between the years 2000 and 2010. RESULTS: We show that UK isolates of S. Mbandaka comprise of one clonal lineage which is adapted to proficient utilisation of metabolites found in soya beans under ambient conditions. We also show that this clonal lineage forms a biofilm at 25 degrees C, suggesting that this serovar maybe well adapted to survival ex vivo, growing in animal feed. Conversely, we show that S. Derby is made of two distinct lineages, L1 and L2. These lineages differ genotypically and phenotypically, being divided by the presence and absence of SPI-23 and the ability to more proficiently invade porcine jejunum derived cell line IPEC-J2. CONCLUSION: The results of this study lend support to the hypothesis that the differences in host ranges of S. Derby and S. Mbandaka are adaptations to pathogenesis, environmental persistence, as well as utilisation of metabolites abundant in their respective host environments. PMID- 26846256 TI - 3-beta-Epsilonrythrodiol isolated from Conyza canadensis inhibits MKN-45 human gastric cancer cell proliferation by inducing apoptosis, cell cycle arrest, DNA fragmentation, ROS generation and reduces tumor weight and volume in mouse xenograft model. AB - The objective of the present study was to investigate the in vitro and in vivo anticancer and apoptotic effects of 3-beta-erythrodiol, a plant-derived triterpene against MKN-45 human gastric cancer cells. In addition, effects on cellular morphology, cell cycle phase distribution, DNA fragmentation, and ROS generation were also elucidated in the current research work. Cytotoxic activity of 3-beta-erythrodiol was demonstrated by MTT cell viability and LDH assay. Cellular morphological study was carried out using phase contrast, fluorescence and scanning electron microscopy. Cell cycle analysis was evaluated by flow cytometry and gel electrophoresis was used to evaluate DNA fragmentation pattern. The results of the present study revealed that 3-beta-erythrodiol induced dose dependent as well as time-dependent anticancer effects in MKN-45 gastric cancer cells. Cellular morphological changes in MKN-45 cells as indicated by fluorescence and scanning electron microscopy were induced by 3-beta-erythrodiol. This triterpene induced both early and late apoptotic features in these cancer cells. 3-beta-Erythrodiol treatment led to sub-G1 cell cycle arrest with a corresponding decrease in S-phase cells and an increase in G2/M phase cells. DNA fragments were evident in gel electrophoresis experiment following 3-beta erythrodiol treatment. It was observed that 0.50 and 1.0 ug/g 3-beta-erythrodiol injection reduced the tumor weight from 1.4 g in PBS-treated group (control) to 0.61 and 0.22 g, respectively. Similarly, 0.50 and 1.0 ug/g 3-beta-erythrodiol injection reduced the tumor volume from 1.5 cm3 in PBS-treated group (control) to 0.91 and 0.31 cm3, respectively. The present investigation indicates that 3-beta erythrodiol exerts anti-proliferative effects in human gastric cancer by inducing early and late apoptosis, cell cycle arrest, and ROS generation. It also decreased the tumor volume and tumor weight in male Balb/c nude mice. PMID- 26846257 TI - Gaining insight into how women conceptualize satisfaction: Western Australian women's perception of their maternity care experiences. AB - BACKGROUND: The concept of maternal satisfaction is challenging, as women's and clinicians' expectations and experiences can differ. Our aim was to investigate women's experiences of maternity care in an urban tertiary obstetric setting, to gain insight into conceptualization of satisfaction across the childbirth continuum. METHODS: This mixed method study was conducted at a public maternity hospital in Western Australia. A questionnaire was sent to 733 women two weeks post birth, which included an invitation for an audio-recorded, telephone interview. Frequency distributions and univariate comparisons were employed for quantitative data. Thematic analysis of interview transcripts was undertaken to extract common themes. RESULTS: A total of 54% (399 of 733) returned the questionnaire. Quantitative results indicated that women were less likely to feel: involved if they did not have a spontaneous vaginal birth (P = 0.020); supported by a midwife if they had a caesarean (P = <0.001); or supported by an obstetrician if they had a spontaneous vaginal birth (P = <0.001). Qualitative findings emerged from 63 interviews which highlighted the influence that organization of care, resources and facilities had on women's satisfaction. These paradigms unfolded as three broad themes constructed by four sub-themes, each illustrating a dichotomy of experiences. The first theme 'how care was provided' encompassed: familiar faces versus a different one every time and the best place to be as opposed to so disappointed. The second theme 'attributes of staff' included: above and beyond versus caring without caring and in good hands as opposed to handled incorrectly. The third theme 'engaged in care' incorporated: explained everything versus did not know why and had a choice as opposed to did not listen to my needs. CONCLUSIONS: Quantitative analysis confirmed that the majority of women surveyed were satisfied. Mode of birth influenced women's perception of being involved with their birth. Being able to explore the diversity of women's experiences in relation to satisfaction with their maternity care in an urban, tertiary obstetric setting has offered greater insight into what women value: a sensitive, respectful, shared relationship with competent clinicians who recognise and strive to provide woman focused care across the childbirth continuum. PMID- 26846263 TI - Examples of individual supported living for adults with intellectual disability. AB - BACKGROUND: This article provides a qualitative account of four models of support for adults with intellectual disability in individual supported living (ISL) arrangements. MATERIALS AND METHODS: Completion of the first 50 evaluations of 150 arrangements for the third phase of the ISL project provided the examples. RESULTS: Four approaches are described: living alone, co-residency, relationship and host family. Within each type, wide variations occur particularly based on security of tenure, formal and informal support and management variations. CONCLUSION: Fifty evaluations so far illustrated a wide range of approaches to ISL, providing evidence of the critical importance of the formal and informal support environment and reinforcing the contention that ISL is appropriate for people with high support needs. PMID- 26846258 TI - Regeneration of the intestinal mucosa in Eimeria and E. Coli challenged broilers supplemented with amino acids. AB - The aim of this study was to evaluate the regeneration of the intestinal mucosa in Eimeria and E. coli challenged broilers supplemented with glutamine, arginine, and threonine. Six hundred male broilers at one d of age from the Cobb strain were utilized. The design was completely randomized using a 2*3 factorial design (unchallenged and challenged and 3 diets). A commercial diet was used as a control and 2 other diets were formulated with glutamine (1.5 and 3% Aminogut(r)), arginine (1 and 2% L-Arginine), and threonine (1 and 2% L threonine). The animals that consumed diets supplemented with amino acids presented better (P<0.05) feed conversion in the period from one to 42 d of age. The ability of cell proliferation and the villus:crypt ratio in response to enteric challenge were greater (P<0.05) for broilers that received diets supplemented with amino acids. High levels of amino acids in the experimental feeds reflected in greater protein levels in poultry house litter, and they did not interfere with ammonia production. The supplementation of diets with trophic amino acids can positively contribute to the regeneration and proliferation of the intestinal mucosa in broilers and to the maintenance of zootechnical performance when submitted to enteric challenges. PMID- 26846265 TI - Over half of English general practices report unmanageable workload. PMID- 26846264 TI - Effectiveness of open bite correction when managing deleterious oral habits in growing children and adolescents: a systematic review and meta-analysis. AB - BACKGROUND/OBJECTIVES: Oral habits are common etiological factors for anterior open bites (AOBs) in growing children and adolescents. The objective of this review was to provide a literature synthesis evaluating the effectiveness of open bite correction in growing individuals with the use of habit-interception appliances. SEARCH METHODS: Electronic searches were conducted on PubMed, Embase, Cochrane Library, Web of Sciences, Scopus, Google Scholar, Scielo, and Lilacs databases. Trials registries were consulted for ongoing trials, and a partial grey literature search was also conducted. SELECTION CRITERIA: The selection criteria included controlled clinical trials enrolling growing subjects who underwent habit-interception orthodontic treatment to correct dental and/or skeletal AOB. DATA COLLECTION ANALYSIS: Data was grouped and analysed descriptively. A meta-analysis was only possible regarding crib therapy effectiveness. Qualitative appraisal was performed according to Cochrane Risk of Bias tool for randomized clinical trials (RCTs) and the MINORS tool for non randomized clinical trials (nRCTs). RESULTS: Two RCTs and nine nRCTs were identified. Most of them presented relevant limitations. Crib therapy demonstrated to be effective (+3.1mm overbite correction). However, most of the dental effects are seemingly lost with time; and the skeletal effects are still controversial. Other habit-interception appliances, such as spurs, were not sufficiently investigated. CONCLUSIONS: Crib therapy appears to be effective on a short time basis. As for other habit-interception appliances, insufficient evidence could not provide reliable conclusions. PMID- 26846266 TI - MicroRNA-96 Regulates Apoptosis by Targeting PDCD4 in Human Glioma Cells. AB - Glioblastoma multiforme, the most common and aggressive form of primary brain tumor, presents a dismal prognosis. MicroRNAs play a critical role in the initiation, progression, and metastasis of cancer; however, the potential biological role of miRNAs in glioblastoma multiforme remains largely unknown. In our study, we found that microRNA-96 is upregulated in glioma tissues than in normal human brains. Transfection of microRNA-96 mimics into glioma cells significantly decreases apoptosis by suppressing PDCD4, a well-known tumor suppressor that is involved in apoptosis. In contrast, knockdown of microRNA-96 enhanced apoptosis. In vivo, microRNA-96 overexpression inhibits the apoptosis and increases tumor growth. These data suggest that microRNA-96 is a potential molecular target for glioma treatment. PMID- 26846269 TI - Adverse reaction to metal bearing leading to femoral stem fractures: a literature review and report of two cases. AB - Metal-on-metal (MoM) bearing in total hip replacement (THR) has a high failure rate due to adverse reaction to metal debris (ARMD). There is a spectrum of soft tissue and bony changes in ARMD including muscle necrosis and osteolysis. In our institution, more than 1500 MoM THRs were implanted since 2003. Recently, we have revised significant numbers of these. We report our experience and management of a mode of failure of MoM THR that has been infrequently reported-the distal femoral stem fracture. We report on two patients who presented with worsening pain attributable to fracture of the femoral stem. Severe femoral osteolysis led to loss of proximal stem support and eventual fatigue fracture of the component. Both patients were revised employing a posterior approach. Bone trephine was used to extract a well-fixed distal stem fragment without any windows. Both patients had successful outcome after revision with excellent pain relief and no complications. PMID- 26846268 TI - Deadly pressure pneumothorax after withdrawal of misplaced feeding tube: a case report. AB - BACKGROUND: Many patients have a nasogastric feeding tube inserted during admission; however, misplacement is not uncommon. In this case report we present, to the best of our knowledge, the first documented fatality from pressure pneumothorax following nasogastric tube withdrawal. CASE PRESENTATION: An 84-year old Caucasian woman with dysphagia and at risk of aspiration underwent routine insertion of a nasogastric feeding tube; however, shortly after insertion she developed respiratory distress. A chest X-ray showed the tube had been misplaced into our patient's right lung. The tube was removed, but our patient died less than an hour after withdrawal. The autopsy report stated that cause of death was tension pneumothorax, which developed following withdrawal of the misplaced feeding tube. CONCLUSIONS: The indications for insertion of nasogastric feeding tubes are many and the procedure is considered harmless; however, if the tube is misplaced there is good reason to be cautious on removal as this can unmask puncture of the pleura eliciting pneumothorax and, as this case report shows, result in an ultimately deadly tension pneumothorax. PMID- 26846267 TI - Combination therapy of tiotropium and ciclesonide attenuates airway inflammation and remodeling in a guinea pig model of chronic asthma. AB - BACKGROUND: The long-acting anticholinergic tiotropium has recently been registered for the treatment of asthma, and its use is associated with a reduction in exacerbation frequency. Anti-inflammatory and anti-remodeling effects of tiotropium have been demonstrated in in vitro and in vivo models. Because tiotropium treatment is used in combination with inhaled corticosteroids, potential additive effects between the two would be clinically relevant. Therefore, the aim of this study was to investigate additive effects between tiotropium and ciclesonide on airway inflammation and remodeling in guinea pig models of asthma. METHODS: Guinea pigs (n = 3-8/group) were sensitized and challenged with ovalbumin in an acute (single challenge) and a chronic model (12 weekly challenges) of allergic asthma. Animals were treated with vehicle, nebulized tiotropium (0.01-0.3 mM) and/or intranasally instilled ciclesonide (0.001-1 mg/kg) before each challenge. Bronchoalveolar lavage fluid and lungs were collected for analysis of airway inflammation and remodeling. RESULTS: Tiotropium and ciclesonide treatment, alone or in combination, did not inhibit airway inflammation in the acute asthma model. In a dose-finding study, low doses of tiotropium and ciclesonide inhibited airway eosinophilia and airway smooth muscle thickening in the chronic asthma model. Threshold doses of 0.01 mM tiotropium (nebulizer concentration) and 0.01 mg/kg ciclesonide were selected to investigate potential additive effects between both drugs. At these doses, tiotropium and ciclesonide did not inhibit airway eosinophilia or airway smooth muscle thickening when administered alone, but significantly inhibited these allergen-induced responses when administered in combination. CONCLUSIONS: Combined treatment with low doses of tiotropium and ciclesonide inhibits airway inflammation and remodeling in a guinea pig model of chronic asthma, suggesting that combined treatment with anticholinergics and corticosteroids may have anti inflammatory and anti-remodeling activity in allergic airway diseases. Since tiotropium is registered as a therapy for asthma added on to corticosteroid treatment, these beneficial effects of the combination therapy may be clinically relevant. PMID- 26846270 TI - A simple technique for hemostasis control after enucleation of deep located liver tumors or after liver trauma. AB - Modern liver techniques allowed the development of segment-based anatomical liver resections. Nevertheless, there is still a place for nonanatomical liver resections. However, in some cases, there is a need for enucleation of deep located liver tumors. The main problem with enucleation of a liver tumor deeply located in the middle of the liver is the control of bleeding resulting from the rupture of small or medium vessels. The authors describe a simple way to control the bleeding without the use of any special instrument or material. This technique can also be used to control bleeding from penetrating liver injury. PMID- 26846271 TI - The PTEN/Akt Signaling Pathway Mediates Myocardial Apoptosis in Swine After Coronary Microembolization. AB - BACKGROUND/AIMS: Phosphatase and the tensin homolog deleted on chromosome ten (PTEN) has been recognized as a promoter of apoptosis in various tissues and has been shown to be upregulated in circumstances of coronary microembolization (CME). We hypothesized that the upregulation of PTEN correlates with CME-induced myocardial apoptosis. METHODS: Swine CME was induced by an intracoronary injection of inert plastic microspheres (diameter of 42 MUm) into the left anterior descending coronary, with or without pretreatment of the PTEN small interfering RNA (siRNA). Echocardiological measurements, a pathological examination, Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining, and Western blotting, were performed to assess their functional, morphological, and molecular effects in CME. RESULTS: PTEN was aberrantly upregulated in cardiomyocytes following CME. Downregulation of PTEN in vivo via siRNA was associated with improved cardiac function and attenuated myocardial apoptosis; concomitantly inhibited the expression of key proapoptotic proteins, such as phosphorylated Bad (p-Bad); cleaved caspase-3; and enhanced the expression of key antiapoptotic proteins, such as phosphorylated protein kinase B (p-Akt). However, there was no difference in the Akt-regulated downstream protein IkappaB kinases (IKKalpha, IKKbeta, and IKKgamma) among the sham, CME, and control siRNA groups. CONCLUSION: This study demonstrates, for the first time, that the PTEN/Akt signaling pathway contributes to cardiomyocyte apoptosis. The data generated from this study provide a rationale for the development of PTEN based therapeutic strategies for CME-induced myocardial injury. PMID- 26846272 TI - Berberine Pretreatment Confers Cardioprotection Against Ischemia-Reperfusion Injury in a Rat Model of Type 2 Diabetes. AB - Preclinical and clinical studies have demonstrated that berberine (BBR) improves diabetic complications and reduces mortality of patients with congestive heart failure. The therapeutic effects of BBR have been reported to be mediated by its regulation of adenosine monophosphate (AMP)-activated protein kinase (AMPK). We previously reported that BBR protects against ischemia-reperfusion injury via regulating AMPK activity in both ischemic and nonischemic areas of the rat heart. Since diabetic hearts are more sensitive to ischemia-reperfusion injury, we examined whether BBR treatment exhibited cardioprotective effects in the diabetic heart. Type 2 diabetic rats were pretreated plus or minus BBR for 7 days and subjected to 30-minute ischemia followed by 120-minute reperfusion. Pretreatment of type 2 diabetic rats with BBR reduced ischemia-reperfusion injury infarct size and attenuated arrhythmia compared to untreated diabetic controls. Subsequent to ischemia-reperfusion, serum triglyceride, total cholesterol, and malondialdehyde levels were reduced by pretreatment of type 2 diabetic rats with BBR compared to untreated diabetic controls. In contrast, serum glucose and superoxide dismutase levels were unaltered. The mechanism for the BBR-mediated cardioprotective effect was examined. Pretreatment with BBR did not alter AMPK activity in ischemic areas at risk but increased AMPK activity in nonischemic areas compared to untreated diabetic controls. The increased AMPK activity in nonischemic areas was due an elevated ratio of AMP to adenosine triphosphate (ATP) and adenosine diphosphate to ATP. In addition, pretreatment with BBR increased protein kinase B (AKT) phosphorylation and reduced glycogen synthase kinase 3beta (GSK3beta) activity in nonischemic areas compared to untreated diabetic controls. These findings indicate that BBR protects the diabetic heart from ischemia-reperfusion injury. In addition, BBR may mediate this cardioprotective effect through AMPK activation, AKT phosphorylation, and GSK3beta inhibition in the nonischemic areas of the diabetic heart. PMID- 26846274 TI - A review of the cellular and molecular effects of extracorporeal shockwave therapy. AB - Extracorporeal shockwave therapy (ESWT) is a novel therapeutic modality and its use in promoting connective tissue repair and analgesic effect has been advocated in the literature. It is convenient, cost-effective, and has negligible complications; it therefore bypasses many of the problems associated with surgical interventions. This paper reviews the proposed mechanisms of action in promoting tissue repair and regeneration as well as analysing its efficacy providing an analgesic effect in clinical applications. Further research will be required to not only identify the underlying mechanisms more precisely, but will also be critical for ensuring consistency across the literature so that the most beneficial treatment protocol can be developed. Extracorporeal shockwave therapy stands as a promising alternative modality in promoting tissue repair. PMID- 26846275 TI - New application of an old drug: Antitumor activity and mechanisms of doxycycline in small cell lung cancer. AB - Small cell lung cancer (SCLC) remains one of the most aggressive tumors with a poor prognosis. The clinical outcome of SCLC patients has reached its plateau with the existing standard treatment and thus new therapies are urgently required. Accumulating evidences have indicated that doxycycline, a commonly used antibiotic, has antitumor activity against several malignancies. However, whether doxycycline has antitumor activity in SCLC and its underlying mechanisms remain unclear. Our investigation demonstrated that doxycycline could significantly inhibit the proliferation and colony formulation of SCLC cells (p<0.05). Furthermore, both Hoechst 33258 dye staining and TUNEL assays indicated that doxycycline could induce remarkable apoptosis of H446 cells in a concentration dependent manner. RT-PCR and western blot assays proved that apoptosis induction effect of doxycycline was achieved via inducing the expression of caspase-3 and bax, as well as attenuating the expression of survivin and bcl-2. Moreover, the wound healing assay and Transwell assay indicated that doxycycline could significantly suppress the migration and invasion of H446 cells in a concentration-dependent manner (p<0.05). ELISA assay proved that the inhibitory effect of doxycycline on the migration and invasion of H446 cells was achieved via decreasing the secretion of MMP-2, MMP-9 and VEGF, as well as increasing the secretion of TIMP-2. Taken together, doxycycline dose-dependently suppressed the proliferation, colony formulation, migration and invasion of SCLC cells, as well as induced apoptosis. These findings encourage further investigations on the potential of doxycycline as a candidate drug for the treatment of SCLC. PMID- 26846273 TI - Effect of parsley (Petroselinum crispum, Apiaceae) juice against cadmium neurotoxicity in albino mice (Mus musculus). AB - BACKGROUND: Parsley was employed as an experimental probe to prevent the behavioral, biochemical and morphological changes in the brain tissue of the albino mice following chronic cadmium (Cd) administration. METHODS: Non anesthetized adult male mice were given parsley juice (Petroselinum crispum, Apiaceae) daily by gastric intubation at doses of 10 and 20 g/kg/day. The animals were divided into six groups: Group A, mice were exposed to saline; Groups B and C, were given low and high doses of parsley juice, respectively; Group D, mice were exposed to Cd; Groups E and F, were exposed to Cd and concomitantly given low and high doses of parsley, respectively. RESULTS: Cd intoxication can cause behavioral abnormalities, biochemical and histopathological disturbances in treated mice. Parsley juice has significantly improved the Cd-associated behavioral changes, reduced the elevation of lipid peroxidation and normalized the Cd effect on reduced glutathione and peroxidase activities in the brain of treated mice. Histological data have supported these foundations whereas Cd treatment has induced neuronal degeneration, chromatolysis and pyknosis in the cerebrum, cerebellum and medulla oblongata. CONCLUSION: The low dose (5 g/kg/day) of parsley exhibited beneficial effects in reducing the deleterious changes associated with Cd treatment on the behavior, neurotransmitters level, oxidative stress and brain neurons of the Cd-treated mice. PMID- 26846276 TI - Regulatory roles of microRNA-21 in fibrosis through interaction with diverse pathways (Review). AB - MicroRNA-21 (miR-21) is a small, non-coding RNA which can regulate gene expression at the post-transcriptional level. While the fibrogenic process is vital in tissue repair, proliferation and transition of fibrogenic cells combined with an imbalance of secretion and degradation of the extracellular matrix results in excessive tissue remodeling and fibrosis. Recent studies have indicated that miR-21 is overexpressed during fibrosis and can regulate the fibrogenic process in a variety of organs and tissues via diverse pathways. The present review summarized the significant roles of miR-21 in fibrosis and discussed the underlying key pathways. PMID- 26846277 TI - Screen-based sedentary behavior and associations with functional strength in 6-15 year-old children in the United States. AB - BACKGROUND: Physical strength is associated with improved health outcomes in children. Heavier children tend to have lower functional strength and mobility. Physical activity can increase children's strength, but it is unknown how different types of electronic media use impact physical strength. METHODS: Data from the NHANES National Youth Fitness Survey (NNYFS) from children ages 6-15 were analyzed in this study. Regression models were conducted to determine if screen-based sedentary behaviors (television viewing time, computer/video game time) were associated with strength measures (grip, leg extensions, modified pull ups, plank) while controlling for potential confounders including child age, sex, BMI z-score, and days per week with 60+ minutes of physical activity. Grip strength and leg extensions divided by body weight were analyzed to provide measures of relative strength together with pull-ups and plank, which require lifting the body. RESULTS: The results from the regression models showed the hypothesized inverse association between TV time and all strength measures. Computer time was only significantly inversely associated with the ability to do one or more pull-ups. CONCLUSIONS: This study shows that television viewing, but not computer/videogames, is inversely associated with measures of child strength while controlling for child characteristics and physical activity. These findings suggest that "screen time" may not be a unified construct with respect to strength outcomes and that further exploration of the potential benefits of reducing television time on children's strength and related mobility is needed. PMID- 26846278 TI - Isatin inhibits the proliferation and invasion of SH-SY5Y neuroblastoma cells. AB - Isatin has been shown to initiate apoptotic processes in SH-SY5Y neuroblastoma cells. The aim of the present study was to investigate whether isatin is also able to alter the proliferation and migratory ability of SH-SY5Y cells. The results demonstrated that the proportion of SH-SY5Y cells in G1 phase was significantly increased following treatment with isatin for 48 h with simultaneous downregulation of cyclin D1 expression. In addition, isatin significantly inhibited cell migration and invasion, along with decreases in matrix metalloproteinase (MMP)2 and MMP9 expression. In addition, isatin reduced the levels of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in a concentration-dependent manner. These results demonstrated that isatin induces G1-phase arrest in SH-SY5Y cells, possibly by decreasing cyclin D1 expression as well as inhibiting their migration and invasiveness, probably by reducing MMP2 and MMP9. These effects may be exerted by isatin via a downregulating the levels of pSTAT3. PMID- 26846280 TI - Erratum to: Genome-wide incorporation dynamics reveal distinct categories of turnover for the histone variant H3.3. PMID- 26846279 TI - A novel dermal matrix generated from burned skin as a promising substitute for deep-degree burns therapy. AB - The extensive skin defects induced by severe burns are dangerous and can be fatal. Currently, the most common therapy is tangential excision to remove the necrotic or denatured areas of skin, followed by skin grafting. Xenogeneic dermal substitutes, such as porcine acellular dermal matrix (ADM), are typically used to cover the burn wounds, and may accelerate wound healing. It is assumed that burned skin that still maintains partial biological activity may be recycled to construct an autologous acellular dermal matrix, termed 'deep-degree burned dermal matrix (DDBDM)'. In theory, DDBDM may avoid the histoincompatibility issues associated with foreign or xenogeneic dermal matrices, and reduce therapy costs by making full use of discarded skin. In the present study, the collagens within prepared DDBDM were thickened, disorganized and partially fractured, however, they still maintained their reticular structure and tensile strength (P<0.01). Through microarray analysis of the cytokines present in ADM and DDBDM, it was determined that the DDBDM did not produce excessive levels of harmful burn toxins. Following 4 weeks of subcutaneous implantation, ADM and DDBDM were incompletely degraded and maintained good integrity. No significant inflammatory reaction or rejection were observed, which indicated that ADM and DDBDM have good histocompatibility. Therefore, DDBDM may be a useful material for the treatment of deep-degree burns. PMID- 26846281 TI - The Bridging Integrator 1 Gene Polymorphism rs744373 and the Risk of Alzheimer's Disease in Caucasian and Asian Populations: An Updated Meta-Analysis. AB - Recent genome-wide association studies have identified an association between the bridging integrator 1 gene (BIN1) rs744373 polymorphism and late-onset Alzheimer's disease (LOAD) in individuals of European ancestry. Additionally, a number of studies have focused on the association between rs744373 and Alzheimer's disease in Caucasian and East Asian populations. However, these results remain inconclusive because of the relatively small sample sizes investigated. Here, we reevaluated this association using samples from seven articles including 22 independent studies comprising 11,832 LOAD patients and 18,133 controls identified by searching PubMed, MEDLINE, and AlzGene databases up to December 2015. We observed no significant heterogeneity between Asian and Caucasian populations. Additive, dominant, and recessive models revealed a significant association between rs744373 and LOAD in the pooled population, while subgroup analysis also identified significant findings in the East Asian population under the additive model (odds ratio (OR) = 1.10, 95 % confidence interval (CI) 1.02-1.19, P = 0.01) and dominant model (OR = 1.13, 95 % CI 1.03 1.25, P = 0.01), but not under the recessive model. The current meta-analysis further supports previous findings that the rs744373 polymorphism may be associated with LOAD risk in Caucasian and Asian populations. To our knowledge, this is the first large meta-analysis to investigate the association between the rs744373 polymorphism and LOAD in East Asian, American, and European populations. PMID- 26846282 TI - MiRNAs are involved in chronic electroacupuncture tolerance in the rat hypothalamus. AB - Acupuncture tolerance is the gradual decrease in analgesic effect due to its prolonged application. However, its mechanism in terms of miRNA is still unknown. To explore the role of miRNAs in electroacupuncture (EA) tolerance of rats using deep sequencing, rats with more than a 50 % increase in tail flick latency (TFL) in response to EA were selected for this experiment. EA tolerance was induced by EA once daily for eight consecutive days. The hypothalami were harvested for deep sequencing. As a result, 49 differentially expressed miRNAs were identified and validated by real-time PCR. Of them, let-7b-5p, miR-148a-3p, miR-124-3p, miR-107 3p, and miR-370-3p were further confirmed to be related to EA tolerance by an intracerebroventricular injection of agomirs or antagomirs of these miRNAs. Potential targets of the 49 miRNAs were enriched in 9 pathways and 282 gene ontology (GO) terms. Five miRNAs were confirmed to participate in EA tolerance probably through the functional categories related to nerve impulse transmission, receptor signal pathways, and gene expression regulation, as well as pathways related to MAPK, neurotrophin, fatty acid metabolism, lysosome, and the degradation of valine, leucine, and isoleucine. Our findings reveal a characterized panel of the differentially expressed miRNAs in the hypothalamus in response to EA and thus provide a solid experimental framework for future analysis of the mechanisms underlying EA-induced tolerance. PMID- 26846283 TI - Methotrexate and Rheumatoid Arthritis: Current Evidence Regarding Subcutaneous Versus Oral Routes of Administration. AB - Methotrexate (MTX) is still considered the drug of choice in rheumatoid arthritis (RA) management. Comparing subcutaneous (MTX SC) and oral (MTX OR) routes of administration is important to optimize the everyday therapeutic strategy in the real-life setting. This review summarizes scientific evidence currently available on this topic. As shown by pharmacokinetic studies, at the same dose level, bioavailability of MTX SC is significantly higher and less variable than that of MTX OR. This difference is even more pronounced for medium-to-high dosages (i.e., >15 mg/week). With regard to clinical response (Disease Activity Score-28, American College of Rheumatology Criteria), randomized, double-blind studies and retrospective or longitudinal analyses in real-life settings showed that MTX SC is more effective than MTX OR. This is true both in MTX-naive patients with early RA, and in patients who switch from MTX OR to MTX SC due to previous treatment failure, lack of efficacy and/or adverse events. Finally, MTX SC has a better tolerability profile than MTX OR, with fewer gastroenterological side effects. Delaying the use of more expensive biological therapies by switching from MTX OR to MTX SC in non-responders might provide cost savings, with relevant implications in the management of patients with RA. FUNDING: Alfa Wassermann. PMID- 26846284 TI - Impact of Reduced Renal Function on the Glucose-Lowering Effects of Luseogliflozin, a Selective SGLT2 Inhibitor, Assessed by Continuous Glucose Monitoring in Japanese Patients with Type 2 Diabetes Mellitus. AB - INTRODUCTION: We investigated the impact of reduced renal function on 24-h glucose variability in Japanese patients with type 2 diabetes mellitus (T2DM) treated with luseogliflozin. METHODS: In this double-blind, placebo-controlled, crossover study, 37 Japanese patients with T2DM [glycated hemoglobin (HbA1c) 7.0 10.0%] and estimated glomerular filtration rate (eGFR) >=45 mL/min/1.73 m(2) were randomized into two groups in which patients first received luseogliflozin then placebo, or vice versa, for 7 days each. Twenty-four-hour glucose variability was measured on day 7 in each period and was compared among patients divided into three groups according to their baseline eGFR (mL/min/1.73 m(2)): normal (>=90; n = 13; normal group), normal-to-mildly reduced renal function (>=75 to <90; n = 12; normal-mild group), and mild-to-moderately reduced renal function (<75; n = 9; mild-moderate group). RESULTS: The mean [95% confidence interval (CI)] placebo subtracted 24-h cumulative urinary glucose excretion (g) was 82.1 (72.7, 91.5), 82.5 (73.4, 91.5), and 62.2 (51.2, 73.3); the placebo-subtracted 24-h mean glucose concentration (mg/dL) was -24.39 (-32.53, -16.26), -28.28 (-39.35, 17.22), and -11.53 (-23.93, 0.86); and the placebo-subtracted peak postprandial glucose (mg/dL) was -26.9 (-46.9, -6.9), -38.1 (-59.6, -16.6), and 1.5 (-25.5, 28.4) in the normal, normal-mild, and mild-moderate groups, respectively. The mean lowest glucose concentrations (placebo vs. luseogliflozin, mg/dL) decreased to similar levels in the normal (115.4 vs. 93.4), normal-mild (121.0 vs. 97.9), and mild-moderate (104.0 vs. 91.1) groups. CONCLUSION: This post hoc subanalysis revealed that although mild-to-moderately reduced renal function attenuated the glucose-lowering effects of luseogliflozin on peak postprandial glucose, it did not attenuate the effects of luseogliflozin on fasting glucose. These findings may explain the smaller increase in urinary glucose excretion in these patients relative to patients with normal renal function or normal-to-moderately reduced renal function. Further studies may be needed to examine these findings in large populations of patients with T2DM and reduced renal function. TRIAL REGISTRATION: JapicCTI-142548. FUNDING: Taisho Pharmaceutical Co., Ltd. PMID- 26846285 TI - Novel ophiostomatalean fungi from galleries of Cyrtogenius africus (Scolytinae) infesting dying Euphorbia ingens. AB - Euphorbia ingens trees have been dying in large numbers in the Limpopo Province of South Africa for approximately 15 years. The ambrosia beetle Cyrtogenius africus is often found infesting diseased and dying trees. The aim of this study was to identify the ophiostomatoid fungi occurring in the galleries of C. africus. Logs infested with this beetle were collected from the KwaZulu-Natal, Limpopo, Mpumalanga, and North West Provinces of South Africa. Fungi belonging to the Ophiostomatales were identified based on morphology and comparison of sequence data for the beta-tubulin, ITS1-5.8S-ITS2 and LSU gene regions. A novel species of Ophiostoma and a novel genus in the Ophiostomatales were identified. Inoculation studies with these fungi produced lesions in the branches of healthy E. ingens trees. PMID- 26846286 TI - Thalassotalea sediminis sp. nov., isolated from coastal sediment. AB - A novel Gram-stain negative, facultatively anaerobic, rod-shaped and yellowish white-pigmented marine bacterium, designated strain N211(T), was isolated from marine sediment obtained off the coastal area of Weihai, China. The cells are approximately 0.4-0.9 * 1.8-3.5 MUm in size and motile by means of a polar flagellum. The strain grows optimally at 33 degrees C, pH 7.5-8.5 and in the presence of 3.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences indicated that strain N211(T) fell within the clade comprising the type strains of species of the genus Thalassotalea. Strain N211(T) was most closely related to Thalassotalea ganghwensis DSM 15355(T) (96.4 %) based on the 16S rRNA gene sequence, and shared 94.4-96.4 % similarity with type strains of all members of the genus Thalassotalea. The predominant isoprenoid quinone of strain N211(T) was identified as ubiquinone-8 (Q-8). The major polar lipids were found to be phosphatidylethanolamine, phosphatidylglycerol and an unidentified lipid. C17:1 w8c, summed feature 3 (C16:1 w7c and/or iso-C 15:0 2 OH) and C16:0 were found to be main cellular fatty acids. The G+C content of the genomic DNA is 39.1 mol%. It is evident from phenotypic data and phylogenetic inference that strain N211(T) represents a novel species of the genus Thalassotalea, for which the name T. sediminis sp. nov. is proposed. The type strain is N211(T) (=KCTC 42588(T) = MCCC 1H00116(T)). PMID- 26846287 TI - The Challenge of Immunoglobulin-G Subclass Deficiency and Specific Polysaccharide Antibody Deficiency--a Dutch Pediatric Cohort Study. AB - PURPOSE: Immunoglobulin(Ig)G-subclass deficiency and specific polysaccharide antibody deficiency (SPAD) are among the most frequent causes of recurrent respiratory infections in children. Little is known about their prevalence, clinical presentation and prognosis. No study has been published in a Western European nor in a mainly non-tertiary cohort until now. Therefore, we performed this observational cohort study in children recruited from secondary and tertiary pediatric practices all over The Netherlands. METHODS: Dutch pediatricians were monthly asked to report patients with IgG-subclass deficiency and/or SPAD. Demographic, clinical and laboratory characteristics were collected. Separate informed consent was asked from parents and children (>= 12 years of age) for annual update of the medical status. RESULTS: 49 children with confirmed IgG subclass deficiency and/or SPAD were included. The majority of children (69%) was reported by four (out of 12) secondary hospitals with a pediatric immunologist in the staff. 45 children had >= 1 low IgG-subclass level and 11 had SPAD. IgG2 deficiency was the most prevalent IgG-subclass deficiency (37/49;76%). 10% of these children already showed bronchiectasis. Two-thirds were male (33/49;67%, p = 0.015). From 10 years of age, only boys were left and only boys showed progressive immunodeficiency during follow-up (11/24; 46%). CONCLUSIONS: This is the first Western-European mainly non-tertiary cohort of children with IgG subclass deficiency and/or SPAD. The disease course is not always benign, especially in boys. Most children were reported and managed in secondary hospitals with a pediatric immunologist in the staff. To identify more patients, the awareness of these diseases among general pediatricians should increase. PMID- 26846288 TI - GTest: a software tool for graphical assessment of empirical distributions' Gaussianity. AB - In the present paper, the novel software GTest is introduced, designed for testing the normality of a user-specified empirical distribution. It has been implemented with two unusual characteristics; the first is the user option of selecting four different versions of the normality test, each of them suited to be applied to a specific dataset or goal, and the second is the inferential paradigm that informs the output of such tests: it is basically graphical and intrinsically self-explanatory. The concept of inference-by-eye is an emerging inferential approach which will find a successful application in the near future due to the growing need of widening the audience of users of statistical methods to people with informal statistical skills. For instance, the latest European regulation concerning environmental issues introduced strict protocols for data handling (data quality assurance, outliers detection, etc.) and information exchange (areal statistics, trend detection, etc.) between regional and central environmental agencies. Therefore, more and more frequently, laboratory and field technicians will be requested to utilize complex software applications for subjecting data coming from monitoring, surveying or laboratory activities to specific statistical analyses. Unfortunately, inferential statistics, which actually influence the decisional processes for the correct managing of environmental resources, are often implemented in a way which expresses its outcomes in a numerical form with brief comments in a strict statistical jargon (degrees of freedom, level of significance, accepted/rejected H0, etc.). Therefore, often, the interpretation of such outcomes is really difficult for people with poor statistical knowledge. In such framework, the paradigm of the visual inference can contribute to fill in such gap, providing outcomes in self explanatory graphical forms with a brief comment in the common language. Actually, the difficulties experienced by colleagues and their request for an effective tool for addressing such difficulties motivated us in adopting the inference-by-eye paradigm and implementing an easy-to-use, quick and reliable statistical tool. GTest visualizes its outcomes as a modified version of the Q-Q plot. The application has been developed in Visual Basic for Applications (VBA) within MS Excel 2010, which demonstrated to have all the characteristics of robustness and reliability needed. GTest provides true graphical normality tests which are as reliable as any statistical quantitative approach but much easier to understand. The Q-Q plots have been integrated with the outlining of an acceptance region around the representation of the theoretical distribution, defined in accordance with the alpha level of significance and the data sample size. The test decision rule is the following: if the empirical scatterplot falls completely within the acceptance region, then it can be concluded that the empirical distribution fits the theoretical one at the given alpha level. A comprehensive case study has been carried out with simulated and real-world data in order to check the robustness and reliability of the software. PMID- 26846289 TI - Metals bioaccumulation in two edible bivalves and health risk assessment. AB - Our aim was to quantify the bioaccumulation of 13 metals in two edible bivalves (Ruditapes decussatus and Paphia undulata) in Lake Timsah, Egypt. A potential human health risk assessment was conducted to evaluate the hazards from bivalve consumption. Fe, Al, Zn, and Sr had the highest concentrations in the bivalve samples. The levels of Cd were much lower than the maximum permissible level, while Pb concentrations in the two bivalves were nearly two times the permissible level. The extent of bioaccumulation factor was site- and species-specific. For low and high bivalve-consuming groups, the estimated daily intake of Pb and Cd ranged from 0.01 to 0.76 MUg/kg/day. For low and high bivalve-consuming groups, hazard quotients (HQs) for metals were found to be less than 1 for both bivalve species, except for Co in the high-consuming group. In conclusion, even though there was no apparent risk to bivalve consumers from being exposed to single metals, there is a risk from being exposed to the 13 studied metals together, especially for high bivalve-consuming groups such as fishermen. PMID- 26846290 TI - A test of biological trait analysis with nematodes and an anthropogenic stressor. AB - Aquatic ecosystems are fundamentally altered by nutrient enrichment, and effective monitoring tools are needed to detect biological responses especially in the early stages of eutrophication. We tested the utility of biological trait analysis (BTA) to quantify the temporal responses of nematodes inhabiting salt marsh creeks that were experimentally enriched with nutrients for 6 years. Feeding, body shape, and tail shape traits were characterized on >6000 nematodes from annual samples from enriched and non-enriched sites. Here, we ask if trait combinations are more effective than single traits in detecting the magnitude and rate of change. We also sought to identify combinations of traits that best distinguish natural from nutrient-induced variation. BTA revealed that feeding, body shape, and all traits combined equally detected the response to nutrient enrichment. Compared to single traits however, BTAs were more sensitive to temporal trends and better distinguished natural variation from the response to nutrient enrichment. Tail shape traits (that might respond to altered sediment texture or geochemistry) were not affected by enrichment, and feeding traits yielded the greatest difference between enriched and reference communities indicating that changes in food resources drove responses. Feeding traits provided the highest quality information content in our study, and the use of feeding traits alone may adequately identify anthropogenic effects in many studies. However, we caution that body shape, tail shape, and feeding traits were strongly interrelated at our study site, and a diversity of trait groups may increase the information content of BTAs in more diverse habitats. PMID- 26846291 TI - Building a strategy for soil protection at local and regional scale--the case of agricultural wastes landspreading. AB - Agricultural wastes (AW) are produced in huge quantities worldwide and may cause detrimental effects on environmental quality, affecting soil, water, and air quality. Given the growing soil degradation worldwide, the need for more food of good quality and therefore the intensified agriculture, it is important to develop recycling plans even for those types of treated AW (e.g., composts) that are not considered hazardous. Two strategic approaches for safe and sustainable landspreading of organic wastes are proposed, depending on wastes properties and hazard potential, i.e., an approach appropriate for traditionally used wastes (manures and composts) and another approach for wastes that are potentially hazardous or hazardous and should only be reused under specific restrictions. Both approaches foresee concrete steps, require close cooperation between farmers and local/regional authorities, and are appropriate to ensure environmental sustainability at AW recycling or disposal areas. Desktop and web application tools are also presented that are anticipated to assist authorities in implementing their monitoring strategies. PMID- 26846292 TI - Atrazine and its metabolites degradation in mineral salts medium and soil using an enrichment culture. AB - An atrazine-degrading enrichment culture was used to study degradation of atrazine metabolites viz. hydroxyatrazine, deethylatrazine, and deisopropylatrazine in mineral salts medium. Results suggested that the enrichment culture was able to degrade only hydroxyatrazine, and it was used as the sole source of carbon and nitrogen. Hydroxyatrazine degradation slowed down when sucrose and/or ammonium hydrogen phosphate were supplemented as the additional sources of carbon and nitrogen, respectively. The enrichment culture could degrade high concentrations of atrazine (up to 110 MUg/mL) in mineral salts medium, and neutral pH was optimum for atrazine degradation. Further, except in an acidic soil, enrichment culture was able to degrade atrazine in three soil types having different physico-chemical properties. Raising the pH of acidic soil to neutral or alkaline enabled the enrichment culture to degrade atrazine suggesting that acidic pH inhibited atrazine-degrading ability. The study suggested that the enrichment culture can be successfully utilized to achieve complete degradation of atrazine and its persistent metabolite hydroxyatrazine in the contaminated soil and water. PMID- 26846293 TI - Spatial and temporal estimation of soil loss for the sustainable management of a wet semi-arid watershed cluster. AB - The ungauged wet semi-arid watershed cluster, Seethagondi, lies in the Adilabad district of Telangana in India and is prone to severe erosion and water scarcity. The runoff and soil loss data at watershed, catchment, and field level are necessary for planning soil and water conservation interventions. In this study, an attempt was made to develop a spatial soil loss estimation model for Seethagondi cluster using RUSLE coupled with ARCGIS and was used to estimate the soil loss spatially and temporally. The daily rainfall data of Aphrodite for the period from 1951 to 2007 was used, and the annual rainfall varied from 508 to 1351 mm with a mean annual rainfall of 950 mm and a mean erosivity of 6789 MJ mm ha(-1) h(-1) year(-1). Considerable variation in land use land cover especially in crop land and fallow land was observed during normal and drought years, and corresponding variation in the erosivity, C factor, and soil loss was also noted. The mean value of C factor derived from NDVI for crop land was 0.42 and 0.22 in normal year and drought years, respectively. The topography is undulating and major portion of the cluster has slope less than 10 degrees , and 85.3% of the cluster has soil loss below 20 t ha(-1) year(-1). The soil loss from crop land varied from 2.9 to 3.6 t ha(-1) year(-1) in low rainfall years to 31.8 to 34.7 t ha(-1) year(-1) in high rainfall years with a mean annual soil loss of 12.2 t ha( 1) year(-1). The soil loss from crop land was higher in the month of August with an annual soil loss of 13.1 and 2.9 t ha(-1) year(-1) in normal and drought year, respectively. Based on the soil loss in a normal year, the interventions recommended for 85.3% of area of the watershed includes agronomic measures such as contour cultivation, graded bunds, strip cropping, mixed cropping, crop rotations, mulching, summer plowing, vegetative bunds, agri-horticultural system, and management practices such as broad bed furrow, raised sunken beds, and harvesting available water using farm ponds and percolation tanks. This methodology can be adopted for estimating the soil loss from similar ungauged watersheds with deficient data and for planning suitable soil and water conservation interventions for the sustainable management of the watersheds. PMID- 26846294 TI - Effects of light shading and climatic conditions on the metabolic behavior of flonicamid in red bell pepper. AB - The degradation behavior of flonicamid and its metabolites (4 trifluoromethylnicotinic acid (TFNA) and N-(4-trifluoromethylnicotinoyl) glycine (TFNG)) was evaluated in red bell pepper over a period of 90 days under glass house conditions, including high temperature, low and high humidity, and in a vinyl house covered with high density polyethylene light shade covering film (35 and 75%). Flonicamid (10% active ingredient) was applied (via foliar application) to all fruits, including those groups grown under normal conditions (glass house) or under no shade cover (vinyl house). Samples were extracted using a Quick, Easy, Cheap, Effective, Rugged, and Safe "QuEChERS" method and analyzed using liquid chromatography-tandem mass spectrometry (LC/MS/MS). The method performance, including linearity, recovery, limits of detection (LOD), and quantitation (LOQ), was satisfactory. Throughout the experimental period, the residual levels of flonicamid and TFNG were not uniform, whereas that of TFNA remained constant. The total sum of the residues (flonicamid and its metabolites) was higher in the vinyl house with shade cover than in the glass house, under various conditions. The total residues were significantly higher when the treatment was applied under high light shade (75%). The flonicamid half-life decreased from 47.2 days (under normal conditions) to 28.4 days (at high temperatures) in the glass house, while it increased from 47.9 days (no shade cover) to 66 days (75% light shading) in the vinyl house. High humidity leads to decreases in the total sum of flonicamid residues in red bell pepper grown in a glass house, because it leads to an increase in the rate of water loss, which in turn accelerates the volatilization of the pesticide. For safety reasons, it is advisable to grow red bell pepper under glass house conditions because of the effects of solar radiation, which increases the rate of flonicamid degradation into its metabolites. PMID- 26846295 TI - Effect of various pneumoperitoneum pressures on femoral vein hemodynamics during laparoscopic cholecystectomy. AB - High intra-abdominal pressure and reverse Trendelenburg position during laparoscopic cholecystectomy (LC) are risk factors for venous stasis in lower extremity. Lower limb venous stasis is one of the major pathophysiological elements involved in the development of peri-operative deep vein thrombosis. Low pressure pneumoperitoneum (7-10 mmHg) has been recommended in patients with limited cardiac, pulmonary or renal reserve. The purpose of this study was to observe the effect of various pneumoperitoneum pressures on femoral vein (FV) hemodynamics during LC. A total of 50 patients undergoing elective LC were enrolled and they were prospectively randomized into two groups containing 25 patients each. In group A high pressure pneumoperitoneum (14 mmHg) and in group B low pressure pneumoperitoneum (8 mmHg) was maintained. Comparison of pre operative and post-operative coagulation profile was done. Preoperative and intraoperative change in femoral vein diameter (FVD) (AP and LAT), cross sectional area (CSA) and peak systolic flow (PSF) during varying pneumoperitoneum pressure was recorded in FV by ultrasound Doppler. First measurement (pre operative) was carried out just after the induction of anesthesia before creation of pneumoperitoneum and second measurement (intra-operative) was taken just before completion of surgery with pneumoperitoneum maintained. Changes in coagulation parameters were less significant at low pressure pneumoperitoneum. There was statistical significant difference in the pre-operative and intra operative values of FVD, CSA and PSF in both groups when analyzed independently (P = 0.00). There was no significant difference in pre-operative values of FVD, CSA and PSF (P > 0.05) among two groups but when the comparison was made between the intra-operative values, there was significant increase in FVD (AP) (P = 0.016), CSA (P = 0.00) and decrease in PSF (P = 0.00) at high pressure pneumoperitoneum. This study provides evidence of using low pressure pneumoperitoneum during LC as changes in FV hemodynamics and coagulation parameters were less pronounced at low pressure pneumoperitoneum. PMID- 26846297 TI - Signaling pathways involved in the effects of HMGB1 on mesenchymal stem cell migration and osteoblastic differentiation. AB - High mobility group box 1 (HMGB1) epxression has been found in the inflammatory microenvironment of fractures. It is well known that HMGB1 acts as a chemoattractant for mesenchymal stem cells (MSCs); however, the effects of HMGB1 on MSC migration and osteoblastic differentiation, and the signaling pathways involved in these effects, have not yet been elucidated. In this study, we aimed to investigate these effects, as well as the signaling mechanisms involved, using in vitro models. We found that HMGB1, in varying concentrations, promoted the osteoblastic differentiation of MSCs, the synthesis of receptor for advanced glycation end products (RAGE) and Toll-like receptor (TLR)2/4, and the activation of the p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF kappaB) signaling pathways. Subsequently, we cultured the MSCs in the appropriate concentration of HMGB1, and determined the signaling pathways involved in the effects of HMGB1 on MSC migration and differentiation, using receptor neutralizing antibodies and signaling pathway inhibitors. From the results of this study, we concluded that HMGB1 promotes MSC migration through the activation of the p38 MAPK signaling pathway, and also promotes MSC differentiation by binding to TLR2/4 and activating the p38 MAPK signaling pathway. These findings elucidate the mechanisms underlying the effects of HMGB1 in the fracture microenvironment, which may provide a theoretical basis for the development of improved clinical treatments for fractures. PMID- 26846296 TI - Physisorption of DNA molecules on chemically modified single-walled carbon nanotubes with and without sonication. AB - We investigated the physisorption phenomenon of single-stranded DNA (ssDNA) molecules onto two types of commercially available chemically functionalized single-walled carbon nanotubes (SWNTs) by atomic force microscopy (AFM) and agarose gel electrophoresis. We found that DNA molecules can adsorb on the water soluble SWNT surfaces without sonication, although sonication treatment has been used for hybridization of DNA and SWNTs in many previous studies. Using our method, damage of DNA molecules by sonication can be avoided. On the other hand, the amount of DNA molecules adsorbed on SWNT surfaces increased when the samples were sonicated. This fact suggests that the sonication is effective not only at debundling of SWNTs, but also at assisting DNA adsorption. Furthermore, DNA adsorption was affected by the types of functionalized SWNTs. In the case of SWNTs functionalized with polyethylene glycol (PEG-SWNT), physisorption of ssDNA molecules was confirmed only by agarose-gel electrophoresis. In contrast, amino terminated SWNTs (NH2-SWNTs) showed a change in the height distribution profile based on AFM observations. These results suggest that DNA molecules tended to adsorb to NH2-SWNT surfaces, although DNA molecules can also adsorb on PEG-SWNT surfaces. Our results revealed fundamental information for developing nanobiodevices using hybrids of DNA and SWNTs. PMID- 26846298 TI - Nurses in municipal care of the elderly act as pharmacovigilant intermediaries: a qualitative study of medication management. AB - OBJECTIVE: To explore registered nurses' experience of medication management in municipal care of the elderly in Sweden, with a focus on their pharmacovigilant activities. DESIGN: A qualitative approach using focus-group discussions was chosen in order to provide in-depth information. Data were analysed by qualitative content analysis. SETTING: Five focus groups in five different long term care settings in two regions in Sweden. SUBJECT: A total of 21 registered nurses (RNs), four men and 17 women, aged 27-65 years, with 4-34 years of nursing experience. RESULTS: The findings reveal that RNs in municipal long-term care settings can be regarded as "vigilant intermediaries" in the patients' drug treatments. They continuously control the work of staff and physicians and mediate between them, and also compensate for existing shortcomings, both organizational and in the work of health care professionals. RNs depend on other health care professionals to be able to monitor drug treatments and ensure medication safety. They assume expanded responsibilities, sometimes exceeding their formal competence, and try to cover for deficiencies in competence, experience, accessibility, and responsibility-taking. CONCLUSION: The RNs play a central but also complex role as "vigilant intermediaries" in the medication monitoring process, including the issue of responsibility. Improving RNs' possibility to monitor their patients' drug treatments would enable them to prevent adverse drug events in their daily practice. New strategies are justified to facilitate RNs' pharmacovigilant activities. KEY POINTS: This study contributes to the understanding of registered nurses' (RNs') role in medication management in municipal care of the elderly (i.e. detecting, assessing, and preventing adverse drug events or any drug-related problems). RNs can be considered to be "vigilant intermediaries" in elderly patients' drug treatments, working at a distance from staff, physicians, and patients. RNs occasionally take on responsibilities that exceed their formal competence, with the patients' best interests in mind. In order to prevent adverse drug events in municipal care of the elderly, new strategies are justified to facilitate RNs' pharmacovigilant activities. PMID- 26846299 TI - Catalyst and solvent-free alkylation of quinoline N-oxides with olefins: A direct access to quinoline-substituted alpha-hydroxy carboxylic derivatives. AB - A catalyst/solvent-free, one-pot and operationally simple method for the synthesis of quinoline-substituted alpha-hydroxy carboxylic derivatives by the hydroxyheteroarylation of olefins with quinoline N-oxides is reported. The reaction features a high atom-economy, mild and reagent/solvent-free conditions, broad substrate scope and good selectivity with high yields. A preliminary mechanistic study to shed light into the reaction pathway was also carried out. PMID- 26846301 TI - Chance fracture in an older patient with positive sagittal imbalance and previous lumbar arthrodesis: what can be done? AB - The Chance fracture occurs frequently in school-aged patients' population and is related to flexion-distraction injury in motor vehicle accidents. It is so called seat-belt syndrome because the seatbelt lies over the abdomen. After sudden deceleration bends the child around the lap belt causing injuries to the abdomen, and the spine (e.g., Chance fracture). The Chance fracture after a low energy fall in elderly patient's population has rarely been reported. We present an 82 years old patient who suffered unrecognized Chance fracture after a low energy fall. The management of this patient with positive sagittal imbalance and previous arthrodesis consisted of decompression, Smith-Petersen osteotomy and posterior pedicle screw instrumentation. PMID- 26846302 TI - Acute nephrotoxicity of aristolochic acid in vitro: metabolomics study for intracellular metabolic time-course changes. AB - Time-course metabolic changes of aristolochic acid nephrotoxicity (AAN) was investigated using acute AAN HK-2 model. And the AAN-related biomarkers were selected. In the results, 11 potential identified biomarkers were selected and validated using multivariate method combined with time-course analysis. Several metabolic pathways, including vitamin metabolism, lipids acalytion, trytophan metabolism and protein degradation were found to be associated with AAN pathology. This research will provide a valuable reference for the discovery of more potential biomarkers of AAN progression in clinic. PMID- 26846303 TI - Extragenital endometriosis: assessment with MR imaging. A pictorial review. AB - Endometriosis is a gynaecologic disease characterized by endometrial tissue outside the uterine cavity. Commonly it affects the pelvic organs. When endometrial nodules or plaques are localized in sites other than the uterus or ovaries, it is termed extragenital endometriosis. Adequate pre-operative assessment is essential for treatment planning. MRI is a non-invasive method with high spatial resolution that allows the multiplanar evaluation of genital and extragenital endometriosis. Herein, we present a pictorial review of a variety of extragenital endometriosis cases, all of which can be encountered in clinical practice. PMID- 26846300 TI - SOX2 suppresses CDKN1A to sustain growth of lung squamous cell carcinoma. AB - Since the SOX2 amplification was identified in lung squamous cell carcinoma (lung SCC), SOX2 transcriptional downstream targets have been actively investigated; however, such targets are often cell line specific. Here, in order to identify highly consensus SOX2 downstream genes in lung SCC cells, we used RNA-seq data from 178 lung SCC specimens (containing tumor and tumor-associated cells) and analyzed the correlation between SOX2 and previously-reported SOX2-controlled genes in lung SCC. In addition, we used another RNA-seq dataset from 105 non small cell lung cancer cell lines (NSCLC; including 4 lung SCC cell lines) and again analyzed the correlation between SOX2 and the reported SOX2-controlled genes in the NSCLC cell lines (no tumor-associated cells). We combined the two analyses and identified genes commonly correlated with SOX2 in both datasets. Among the 99 genes reported as SOX2 downstream and/or correlated genes, we found 4 negatively-correlated (e.g., CDKN1A) and 11 positively-correlated genes with SOX2. We used biological studies to demonstrate that CDKN1A was suppressed by SOX2 in lung SCC cells. G1 cell cycle arrest induced by SOX2 siRNA was rescued by CDKN1A siRNA. These results indicate that the tumorigenic effect of SOX2 in lung SCC cells is mediated in part by suppression of CDKN1A. PMID- 26846304 TI - CW EPR and 9 GHz EPR imaging investigation of stable paramagnetic species and their antioxidant activities in dry shiitake mushroom (Lentinus edodes). AB - We investigated the antioxidant activities and locations of stable paramagnetic species in dry (or drying) shiitake mushroom (Lentinus edodes) using continuous wave (CW) electron paramagnetic resonance (EPR) and 9 GHz EPR imaging. CW 9 GHz EPR detected paramagnetic species (peak-to-peak linewidth (DeltaHpp) = 0.57 mT) in the mushroom. Two-dimensional imaging of the sharp line using a 9 GHz EPR imager showed that the species were located in the cap and shortened stem portions of the mushroom. No other location of the species was found in the mushroom. However, radical locations and concentrations varied along the cap of the mushroom. The 9 GHz EPR imaging determined the exact location of stable paramagnetic species in the shiitake mushroom. Distilled water extracts of the pigmented cap surface and the inner cap of the mushroom showed similar antioxidant activities that reduced an aqueous solution of 0.1 mM 4-hydroxy 2,2,6,6-tetramethylpiperidin-1-oxyl. The present results suggest that the antioxidant activities of the edible mushroom extracts are much weaker than those of ascorbic acid. Thus, CW EPR and EPR imaging revealed the location and distribution of stable paramagnetic species and the antioxidant activities in the shiitake mushroom for the first time. PMID- 26846305 TI - Fulfilling an Unmet Need: Roles for Clinical Pharmacists in Preconception Care. AB - Preconception care refers to a set of interventions that identify and address biomedical, behavioral, and social risks to a woman's health that may negatively impact a future pregnancy. A great need for preconception care currently exists in the United States, and women's attitudes about discussions with health care providers about healthy and safe pregnancies are positive. Clinical pharmacists are well positioned to work with other health care and public health professionals to ensure that all women of childbearing potential have access to preconception care. As part of the collaborative health care team, clinical pharmacists can directly provide services or support and referrals to other members of the health care team or to community resources through clinical community linkages. Specifically, clinical pharmacists can provide education, counseling, and/or services to women to address family planning, medication and disease state management, immunizations, screenings, health promotion, and substance use. Clinical pharmacists can also impact preconception care through drug information services, advocacy, and research. Preconception care services can be incorporated into daily pharmacy practice, and there are potential means for reimbursement. Multiple roles exist for clinical pharmacists to fulfill unmet needs in preconception care. PMID- 26846306 TI - Myocardial Regional Interstitial Fibrosis is Associated With Left Intra Ventricular Dyssynchrony in Patients With Heart Failure: A Cardiovascular Magnetic Resonance Study. AB - Left ventricular (LV) dyssynchrony is associated with poor prognosis in patients with heart failure (HF). The mechanisms leading to LV dyssynchrony are not fully elucidated. This study evaluates whether myocardium regional variation in interstitial fibrosis is associated with LV dyssynchrony. Forty-two patients with systolic heart failure (SHF), 76 patients with heart failure with preserved ejection fraction (HFpEF) and 20 patients without HF received cardiovascular magnetic resonance imaging (MRI) study. LV was divided into 18 segments by short axis view. In each segment, regional extracellular volume fraction (ECV) and the time taken to reach minimum regional volume (Tmv) were derived. Intra-LV dyssynchrony were represented by maximum difference (Dysyn_max) and standard deviation (Dysyn_sd) of all Tmv. The results showed that among the covariates, only age (1.87, 95% CI: 0.61-3.13, p = 0.004) and ECV (3.77, 95% CI: 2.72-4.81, p < 0.001) were positively associated with Tmv. The results remained robust in certain subgroups. In conclusion, we demonstrated that LV myocardium regional variation in interstitial fibrosis is closely related to LV intra-ventricular dyssynchrony irrespective of the LV global function. These data might help explain the pathophysiology of LV dyssynchrony and it's underlying mechanisms leading to poor prognosis. PMID- 26846308 TI - mTORC2 is a tyrosine kinase. PMID- 26846309 TI - Effects of Poloxamer 188 on red blood cell membrane properties in sickle cell anaemia. AB - Vaso-occlusive crisis (VOC) is the main acute complication in sickle cell anaemia (SS) and several clinical trials are investigating different drugs to improve the clinical severity of SS patients. A phase III study is currently exploring the profit of Velopoloxamer in SS during VOCs. We analysed, in-vitro, the effect of poloxamer (P188) on red blood cell (RBC) properties by investigating haemorheology, mechanical and adhesion functions using ektacytometry, microfluidics and dynamic adhesion approaches, respectively. We show that poloxamer significantly reduces blood viscosity, RBC aggregation and adhesion to endothelial cells, supporting the beneficial use of this molecule in SS therapy. PMID- 26846307 TI - Cisplatin resistance in gastric cancer cells is associated with HER2 upregulation induced epithelial-mesenchymal transition. AB - Cisplatin remains to be primary chemotherapeutic drug for gastric cancer patients, especially for advanced stage ones. However, primary or acquired resistance often occurs with the mechanisms being not well understood, which results in relapse of the cancer and poor survival. Herein, we found that HER2 upregulation was associated with cisplatin resistance. We observed that cisplatin resistant gastric cancer cells underwent a morphological change similar to epithelial-mesenchymal transition (EMT) which is mediated by HER2 overexpression. When specific monoclonal antibody Herceptin, small molecular targeted drug CP724714, or small interfering RNA against HER2 was applied, the EMT-like phenotypic change was dramatically reversed. More importantly, the IC50 and Resistance Index of resistant gastric cancer cells to cisplatin were also decreased by any of these treatments.We demonstrated that expression and amplification of HER2 positively correlated with expression of EMT-related transcription factor Snail in gastric cancer tissues. Furthermore, for the first time, we found that HER2/Snail double positive gastric cancer patients had poorer survival than single positive or double negative counterparts, which provided experimental evidence for the necessity of HER2/Snail double testing in gastric cancer. In conclusion, this study provides some clues of the association of cisplatin resistance with HER2 upregulation-induced EMT in gastric cancer cells. PMID- 26846310 TI - New ZrO2/Al2O3 Nanocomposite Fabricated from Hybrid Nanoparticles Prepared by CO2 Laser Co-Vaporization. AB - Alumina toughened zirconia (ATZ) and zirconia toughened alumina (ZTA) are currently the materials of choice to meet the need for tough, strong, and bioinert ceramics for medical devices. However, the mechanical properties of ZrO2/Al2O3 dispersion ceramics could be considerably increased by reducing the corresponding grain sizes and by improving the homogeneity of the phase dispersion. Here, we prepare nanoparticles with an intraparticular phase distribution of Zr(1-x)Al(x)O(2-x/2) and (gamma-, delta-)Al2O3 by the simultaneous gas phase condensation of laser co-vaporized zirconia and alumina raw powders. During subsequent spark plasma sintering the zirconia defect structures and transition alumina phases transform to a homogeneously distributed dispersion of tetragonal ZrO2 (52.4 vol%) and alpha-Al2O3 (47.6 vol%). Ceramics sintered by spark plasma sintering are completely dense with average grain sizes in the range around 250 nm. Outstanding mechanical properties (flexural strength sigmaf = 1500 MPa, fracture toughness KIc = 6.8 MPa m(1/2)) together with a high resistance against low temperature degradation make these materials promising candidates for next generation bioceramics in total hip replacements and for dental implants. PMID- 26846311 TI - From Allergens to Battery Anodes: Nature-Inspired, Pollen Derived Carbon Architectures for Room- and Elevated-Temperature Li-ion Storage. AB - The conversion of allergic pollen grains into carbon microstructures was carried out through a facile, one-step, solid-state pyrolysis process in an inert atmosphere. The as-prepared carbonaceous particles were further air activated at 300 degrees C and then evaluated as lithium ion battery anodes at room (25 degrees C) and elevated (50 degrees C) temperatures. The distinct morphologies of bee pollens and cattail pollens are resembled on the final architecture of produced carbons. Scanning Electron Microscopy images shows that activated bee pollen carbon (ABP) is comprised of spiky, brain-like, and tiny spheres; while activated cattail pollen carbon (ACP) resembles deflated spheres. Structural analysis through X-ray diffraction and Raman spectroscopy confirmed their amorphous nature. X-ray photoelectron spectroscopy analysis of ABP and ACP confirmed that both samples contain high levels of oxygen and small amount of nitrogen contents. At C/10 rate, ACP electrode delivered high specific lithium storage reversible capacities (590 mAh/g at 50 degrees C and 382 mAh/g at 25 degrees C) and also exhibited excellent high rate capabilities. Through electrochemical impedance spectroscopy studies, improved performance of ACP is attributed to its lower charge transfer resistance than ABP. Current studies demonstrate that morphologically distinct renewable pollens could produce carbon architectures for anode applications in energy storage devices. PMID- 26846312 TI - Forest succession and population viability of grassland plants: long repayment of extinction debt in Primula veris. AB - Time lags in responses of organisms to deteriorating environmental conditions delay population declines and extinctions. We examined how local processes at the population level contribute to extinction debt, and how cycles of habitat deterioration and recovery may delay extinction. We carried out a demographic analysis of the fate of the grassland perennial Primula veris after the cessation of grassland management, where we used either a unidirectional succession model for forest habitat or a rotation model with a period of forest growth followed by a clear-cut and a new successional cycle. The simulations indicated that P. veris populations may have an extinction time of decades to centuries after a detrimental management change. A survey of the current incidence and abundance of P. veris in sites with different histories of afforestation confirmed the simulation results of low extinction rates. P. veris had reduced incidence and abundance only at sites with at least 100 years of forest cover. Time to extinction in simulations was dependent on the duration of the periods with favourable and unfavourable conditions after management cessation, and the population sizes and growth rates in these periods. Our results thus suggest that the ability of a species to survive is a complex function of disturbance regimes, rates of successional change, and the demographic response to environmental changes. Detailed demographic studies over entire successional cycles are therefore essential to identify the environmental conditions that enable long term persistence and to design management for species experiencing extinction debts. PMID- 26846313 TI - Plant nitrogen concentration and isotopic composition in residential lawns across seven US cities. AB - Human drivers are often proposed to be stronger than biophysical drivers in influencing ecosystem structure and function in highly urbanized areas. In residential land cover, private yards are influenced by individual homeowner preferences and actions while also experiencing large-scale human and biophysical drivers. We studied plant nitrogen (%N) and N stable isotopic composition (delta(15)N) in residential yards and paired native ecosystems in seven cities across the US that span major ecological biomes and climatic regions: Baltimore, Boston, Los Angeles, Miami, Minneapolis-St. Paul, Phoenix, and Salt Lake City. We found that residential lawns in three cities had enriched plant delta(15)N (P < 0.03) and in six cities higher plant N (%) relative to the associated native ecosystems (P < 0.05). Plant delta(15)N was progressively depleted across a gradient of urban density classes in Baltimore and Boston (P < 0.05). Lawn fertilization was associated with depleted plant delta(15)N in Boston and Los Angeles (P < 0.05), and organic fertilizer additions were associated with enriched plant delta(15)N in Los Angeles and Salt Lake City (P < 0.04). Plant delta(15)N was significantly enriched as a function of housing age in Baltimore (r (2) = 0.27, P < 0.02), Boston (r (2) = 0.27, P < 0.01), and Los Angeles (r (2) = 0.34, P < 0.01). These patterns in plant delta(15)N and plant N (%) across these cities suggests that N sources to lawns, as well as greater rates of N cycling combined with subsequent N losses, may be important drivers of plant N dynamics in lawn ecosystems at the national scale. PMID- 26846314 TI - Evaluation of the Destruction of the Harmful Cyanobacteria, Microcystis aeruginosa, with a Cavitation and Superoxide Generating Water Treatment Reactor. AB - Cyanobacterial/Harmful Algal Blooms are a major issue for lakes and reservoirs throughout the U.S.A. An effective destructive technology could be useful to protect sensitive areas, such as areas near water intakes. The study presented in this article explored the use of a reactor called the KRIA Water Treatment System. The reactor focuses on the injection of superoxide (O2 (-)), which is generated electrochemically from the atmosphere, into the water body. In addition, the injection process generates a significant amount of cavitation. The treatment process was tested in 190-L reactors spiked with water from cyanobacterial contaminated lakes. The treatment was very effective at destroying the predominant species of cyanobacteria, Microcystis aeruginosa, organic matter, and decreasing chlorophyll concentration. Microcystin toxin concentrations were also reduced. Data suggest that cavitation alone was an effective treatment, but the addition of superoxide improved performance, particularly regarding removal of cyanobacteria and reduction of microcystin concentration. PMID- 26846315 TI - Defining the bone morphometry, micro-architecture and volumetric density profile in osteopenic vs non-osteopenic adolescent idiopathic scoliosis. AB - PURPOSE: Osteopenia has been widely reported in about 30 % of girls with adolescent idiopathic scoliosis (AIS). However, the bone quality profile of the 70 % non-osteopenic AIS defined by areal bone mineral density (BMD) with conventional dual-energy X-ray absorptiometry (DXA) has not been adequately studied. Our purpose was to verify whether abnormal volumetric BMD (vBMD) and bone structure (morphometry and micro-architecture) also existed in the non osteopenic AIS when compared with matched controls using both DXA and high resolution peripheral computed tomography (HR-pQCT). METHODS: This was a case control cross-sectional study. 257 AIS girls with a mean age of 12.7 (SD = 0.8) years old and 187 age- and gender-matched normal controls with an average age of 12.9 (SD = 0.5) years old were included. Areal BMD (aBMD) and bone quality were measured with standard DXA and HR-pQCT, respectively. The parameters of HR-pQCT could be categorized as bone morphometry, vBMD and bone micro-architecture. The results were compared between the osteopenic AIS and osteopenic control, and between the non-osteopenic AIS and non-osteopenic control. RESULTS: In addition to the lower aBMD and vBMD, osteopenic AIS showed significantly greater cortical perimeter and trabecular area than the osteopenic control even after adjustments of age (P < 0.05). Non-osteopenic AIS also showed significantly lower aBMD together with lower cortical area, thickness and vBMD than the non-osteopenic control (P < 0.05). After adjustments of age, cortical area and vBMD, and trabecular number and separation continued to show statistical significance (P < 0.05). Both the osteopenic and non-osteopenic AIS subgroups revealed significant abnormal bone quality parameters from that in the control group after adjustments of age and aBMD with multi-linear regression analysis (P < 0.05). CONCLUSIONS: The present study specifically defined the abnormal profile of bone quality in the osteopenic and non-osteopenic AIS for the first time. Both the osteopenic and non-osteopenic AIS were likely to have relatively lower bone mineral status and abnormal bone morphometry, micro-architecture and volumetric density profile compared with their normal matched controls. The observed abnormalities were suggestive of decreased endocortical bone apposition or active endocortical resorption that could affect the mechanical bone strength in AIS. The underlying pathomechanism might be attributed to abnormal bone modeling/remodeling that could be associated with the etiopathogenesis of AIS. PMID- 26846316 TI - How to use the nominal group and Delphi techniques. AB - Introduction The Nominal Group Technique (NGT) and Delphi Technique are consensus methods used in research that is directed at problem-solving, idea-generation, or determining priorities. While consensus methods are commonly used in health services literature, few studies in pharmacy practice use these methods. This paper provides an overview of the NGT and Delphi technique, including the steps involved and the types of research questions best suited to each method, with examples from the pharmacy literature. Methodology The NGT entails face-to-face discussion in small groups, and provides a prompt result for researchers. The classic NGT involves four key stages: silent generation, round robin, clarification and voting (ranking). Variations have occurred in relation to generating ideas, and how 'consensus' is obtained from participants. The Delphi technique uses a multistage self-completed questionnaire with individual feedback, to determine consensus from a larger group of 'experts.' Questionnaires have been mailed, or more recently, e-mailed to participants. When to use The NGT has been used to explore consumer and stakeholder views, while the Delphi technique is commonly used to develop guidelines with health professionals. Method choice is influenced by various factors, including the research question, the perception of consensus required, and associated practicalities such as time and geography. Limitations The NGT requires participants to personally attend a meeting. This may prove difficult to organise and geography may limit attendance. The Delphi technique can take weeks or months to conclude, especially if multiple rounds are required, and may be complex for lay people to complete. PMID- 26846317 TI - The need to implement an efficient biomass fractionation and full utilization based on the concept of "biorefinery" for a viable economic utilization of microalgae. AB - In the present work, microalgae strains, such as Scenedesmus obliquus and Phaeodactylum tricornutum grown in indoor/outdoor photobioreactors (PBRs) and in open ponds (this is the first study on such strains cultivated in the local Southern Italy climatic conditions), were fully analyzed for their protein content, carbohydrates, lipids, and fatty acid profile in order to assess their potential use for the production of biofuels, chemicals, and omega-3, and as animal feed and human food. They are compared with Nannochloropsis sp. (commercial sample) which was fully analyzed in our laboratory and Chlorella (literature data). An economic evaluation was carried out, demonstrating that the cultivation of microalgae for the production of only biofuels will not match the economic standards. Conversely, if chemicals are also produced applying the biorefinery concept and using wastewater as a source of nutrients, it will be possible to have a good positive return from microalgae. PMID- 26846318 TI - Uptake and decomposition of the herbicide propanil in the plant Bidens pilosa L. dominating in the Yangtze Three Gorges Reservoir (TGR), China. AB - Propanil (3',4'-dichloropropionanilide) is a selective post emergence herbicide for controlling broad leaf and grass weeds in rice (Oryza sativa L.). After being taken up by plants, the fate of propanil in decomposing plant material is of particular importance to the phytoremediation of the environment. Therefore, we investigated the biotransformation of propanil in the plant Bidens pilosa under conditions close to those present in the Three Gorges Reservoir (TGR), China. Plants pre-treated with 14C-ring-labeled propanil were either (treatment a) directly submerged in TGR water for 90 days or (treatment b) pre-extracted with organic solvents, and subsequently only insoluble materials and non-extractable residues (NER) of the pesticide fractions were similarly incubated. After incubation in TGR water (treatment a), 30 % of applied radioactivity was released into water and simultaneously, amounts of NER in the plant debris appeared to increase with time finally amounting to 40 % of applied 14C. The radioactivity contained in the extractable fractions were identified as propanil, 3,4 dichloroaniline (DCA), and N-beta-D-glucopyranosyl-3,4-dichloroaniline (DCA-Glu). In treatment b, significant 14C amounts were released to the water (6 % of applied 14C) and the solubilized radioactivity fractions were demonstrated to agree with those found in the extractable fractions. Therefore, if residues of the pesticide propanil are taken up by plants, it may enter again the aquatic environment after plant death and submergence. This phenomenon may have a potential impact on aquatic organisms, which to our knowledge has not been reported before. As plant uptake and degradation of xenobiotics are recognized as detoxification, we consider B. pilosa with its high uptake potential, at least for propanil, as suitable species for phytoremediation. PMID- 26846319 TI - Provider, father, and bro--Sedentary Maori men and their thoughts on physical activity. AB - BACKGROUND: Maori (indigenous peoples of New Zealand) men have a disproportionate prevalence of lifestyle-related illnesses and are targeted for national physical activity initiatives. While physical activity impacts on physical and mental health and overall wellbeing, current approaches to health promotion often lack cultural relevance. Having better understanding and incorporating relevant cultural values and motivators into program designs could improve the success of health initiatives for indigenous and minority men. Nevertheless, little is known about Maori men's preferences, attitudes, or perspectives about physical activity, which are often interpreted through a colonized or dominant Western lens. Understanding perspectives of those groups whose values do not align with dominant cultural approaches will better equip health promoters and trainers to develop relevant community initiatives and private programs for indigenous and minority men. METHODS: An indigenous research approach informed a qualitative study with 18 sedentary, 'overweight' Maori men aged 28 to 72 years. From 2014 to 2015 these men participated in three focus group discussions aimed at understanding their views about physical activity and exercise. Data were thematically analysed and interpeted using a Maori worldview. RESULTS: Four key themes were identified - Cameraderie and 'Bro-ship'; Adulthood Distractions and Priorities; Problems with Contemporary Gym Culture; and Provider Orientation. Key motivators for physical activity included a sense of 'brotherhood' in sport and physical activity and accountability to others. Participants reported the need to highlight the value of people and relationships, and having an orientation to the collective to enhance physical activity experiences for Maori men in general. Modern lifestyle distractions (such as being time deficient, and family responsibilities) along with other priorities contributed to difficulties incorporating physical activity into their daily lives. In addition, particular aspects and characteristics of the modern fitness culture and gym environment acted as barriers to adherence to physical activity. CONCLUSIONS: Sedentary Maori men understand the importance of physical activity well, and have a desire to be more active. Nevertheless, they find it difficult to do so while balancing other priorities, especially cultural obligations to community and whanau (immediate and wider family). This research provides valuable insight for those promoting physical activity or designing health initiatives so that they better resonate with indigenous and minority men. PMID- 26846320 TI - Oxaliplatin pharmacokinetics on hemodialysis in a patient with diffuse large B cell lymphoma. PMID- 26846321 TI - Ixazomib: First Global Approval. AB - Ixazomib (Ninlaro((r))) is an orally bioavailable, reversible proteasome inhibitor developed by Millennium Pharmaceuticals, Inc. (now Takeda Oncology). Ixazomib acts by binding to and inhibiting the beta5 subunit of the 20S proteasome. In November 2015, the US FDA approved ixazomib for use in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Ixazomib is under regulatory review for this indication in the EU. Phase III development of ixazomib is underway worldwide for newly-diagnosed multiple myeloma (in patients who are not eligible for stem cell transplant, or as maintenance therapy) and for relapsed or refractory systemic light chain (AL) amyloidosis. Ixazomib is also under phase I-II development for the treatment of several other haematological and non-haematological malignancies, graft-versus-host disease and lupus nephritis. This article summarizes the milestones in the development of ixazomib leading to this first approval for multiple myeloma. PMID- 26846322 TI - Selexipag: First Global Approval. AB - Selexipag (Uptravi((r))) is a highly selective, long-acting, nonprostanoid, prostacyclin receptor agonist that is being developed by Actelion Pharmaceuticals Ltd and Nippon Shinyaku. Oral selexipag is approved in the USA for the treatment of pulmonary arterial hypertension (PAH; WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH. It has subsequently been approved in Canada for the long-term treatment of PAH, and received a positive opinion in the EU for the treatment of PAH in adult patients with WHO functional class II-III. Selexipag received orphan drug designation for the treatment of PAH in Japan in 2014 and is in undergoing regulatory review in several countries for use in this indication. In the large, event-driven, phase III GRIPHON trial, selexipag reduced the risk of the primary composite endpoint of death or a complication related to PAH (whichever occurred first) by 40 % compared with placebo in patients with PAH (80 % were also receiving stable dosages of an endothelin receptor antagonist and/or a phosphodiesterase 5 inhibitor). This article summarizes the milestones in the development of selexipag leading to this first approval for PAH. PMID- 26846323 TI - Pembrolizumab: A Review in Advanced Melanoma. AB - Pembrolizumab (Keytruda((r))) is a humanized monoclonal antibody against programmed death receptor-1 (PD-1), a key immunoinhibitory checkpoint protein implicated in down-regulating anti-tumour immune responses. This intravenous drug is indicated for the treatment of advanced (unresectable or metastatic) melanoma, on the basis of its clinical benefit in this setting in the phase I KEYNOTE 001 trial (expansion cohorts) and the phase II and III trials, KEYNOTE 002 and 006. These studies were conducted in ipilimumab-naive and/or ipilimumab-experienced patients and assessed varying pembrolizumab regimens administered every 2 or 3 weeks, all of which helped to determine the recommended dosage of 2 mg/kg every 3 weeks. In the trials with active comparator arms, pembrolizumab regimens significantly improved progression-free survival (PFS), overall survival (OS) and overall response rates (ORR) relative to ipilimumab in ipilimumab-naive patients (KEYNOTE 006), and significantly improved PFS and ORR, but not OS (although OS data are immature), relative to chemotherapy in ipilimumab-refractory patients, who had also received BRAF/MEK inhibitor therapy if BRAF-mutation positive (KEYNOTE 002). Pembrolizumab has an acceptable tolerability profile, with immune related adverse events that are generally manageable/reversible. Thus, pembrolizumab is a valuable treatment option for patients with advanced melanoma, including those who have progressed on ipilimumab and BRAF/MEK inhibitors. PMID- 26846324 TI - Daily Enteral DHA Supplementation Alleviates Deficiency in Premature Infants. AB - Docosahexaenoic acid (DHA) is an essential fatty acid (FA) important for health and neurodevelopment. Premature infants are at risk of DHA deficiency and circulating levels directly correlate with health outcomes. Most supplementation strategies have focused on increasing DHA content in mother's milk or infant formula. However, extremely premature infants may not reach full feedings for weeks and commercially available parenteral lipid emulsions do not contain preformed DHA, so blood levels decline rapidly after birth. Our objective was to develop a DHA supplementation strategy to overcome these barriers. This double blind, randomized, controlled trial determined feasibility, tolerability and efficacy of daily enteral DHA supplementation (50 mg/day) in addition to standard nutrition for preterm infants (24-34 weeks gestational age) beginning in the first week of life. Blood FA levels were analyzed at baseline, full feedings and near discharge in DHA (n = 31) or placebo supplemented (n = 29) preterm infants. Term peers (n = 30) were analyzed for comparison. Preterm infants had lower baseline DHA levels (p < 0.0001). Those receiving DHA had a progressive increase in circulating DHA over time (from 3.33 to 4.09 wt% or 2.88 to 3.55 mol%, p < 0.0001) while placebo-supplemented infants (receiving standard neonatal nutrition) had no increase over time (from 3.35 to 3.32 wt% or 2.91 to 2.87 mol%). Although levels increased with additional DHA supplementation, preterm infants still had lower blood DHA levels than term peers (4.97 wt% or 4.31 mol%) at discharge (p = 0.0002). No differences in adverse events were observed between the groups. Overall, daily enteral DHA supplementation is feasible and alleviates deficiency in premature infants. PMID- 26846326 TI - Erratum to: Effects of Global Postural Reeducation on gait kinematics in parkinsonian patients: a pilot randomized three-dimensional motion analysis study. PMID- 26846325 TI - Reduced Mitochondrial Function in Human Huntington Disease Lymphoblasts is Not Due to Alterations in Cardiolipin Metabolism or Mitochondrial Supercomplex Assembly. AB - Huntington's Disease (HD) is an autosomal dominant disease that occurs as a result of expansion of the trinucleotide repeat CAG (glutamine) on the HTT gene. HD patients exhibit various forms of mitochondrial dysfunction within neurons and peripheral tissues. Cardiolipin (Ptd2Gro) is a polyglycerophospholipid found exclusively in mitochondria and is important for maintaining mitochondrial function. We examined if altered Ptd2Gro metabolism was involved in the mitochondrial dysfunction associated with HD. Mitochondrial basal respiration, spare respiratory capacity, ATP coupling efficiency and rate of glycolysis were markedly diminished in Epstein-Barr virus transformed HD lymphoblasts compared to controls (CTRL). Mitochondrial supercomplex formation and Complex I activity within these supercomplexes did not vary between HD patients with different length of CAG repeats and appeared unaltered compared to CTRL. In contrast, in vitro Complex I enzyme activity in mitochondrial enriched samples was reduced in HD lymphoblasts compared to CTRL. The total cellular pool size of Ptd2Gro and its synthesis/remodeling from [(3)H]acetate/[(14)C]oleate were unaltered in HD lymphoblasts compared to CTRL. In addition, the molecular species of Ptd2Gro were essentially unaltered in HD lymphoblasts compared to CTRL. We conclude that compared to CTRL lymphoblasts, HD lymphoblasts display impaired mitochondrial basal respiration, spare respiratory capacity, ATP coupling efficiency and rate of glycolysis with any pathological CAG repeat length, but this is not due to alterations in Ptd2Gro metabolism. We suggest that HD patient lymphoblasts may be a useful model to study defective energy metabolism that does not involve alterations in Ptd2Gro metabolism. PMID- 26846327 TI - Why do people google movement disorders? An infodemiological study of information seeking behaviors. AB - Millions of people worldwide everyday search Google or Wikipedia to look for health-related information. Aim of this study was to evaluate and interpret web search queries for terms related to movement disorders (MD) in English-speaking countries and their changes over time. We analyzed information regarding the volume of online searches in Google and Wikipedia for the most common MD and their treatments. We determined the highest search volume peaks to identify possible relation with online news headlines. The volume of searches for some queries related to MD entered in Google enormously increased over time. Most queries were related to definition, subtypes, symptoms and treatment (mostly to adverse effects, or alternatively, to possible alternative treatments). The highest peaks of MD search queries were temporally related to news about celebrities suffering from MD, to specific mass-media events or to news concerning pharmaceutic companies or scientific discoveries on MD. An increasing number of people use Google and Wikipedia to look for terms related to MD to obtain information on definitions, causes and symptoms, possibly to aid initial self-diagnosis. MD information demand and the actual prevalence of different MDs do not travel together: web search volume may mirrors patients' fears and worries about some particular disorders perceived as more serious than others, or may be driven by release of news about celebrities suffering from MD, "breaking news" or specific mass-media events regarding MD. PMID- 26846329 TI - Calibration transfer via an extreme learning machine auto-encoder. AB - In order to solve the spectra standardization problem in near-infrared (NIR) spectroscopy, a Transfer via Extreme learning machine Auto-encoder Method (TEAM) has been proposed in this study. A comparative study among TEAM, piecewise direct standardization (PDS), generalized least squares (GLS) and calibration transfer methods based on canonical correlation analysis (CCA) was conducted, and the performances of these algorithms were benchmarked with three spectral datasets: corn, tobacco and pharmaceutical tablet spectra. The results show that TEAM is a stable method and can significantly reduce prediction errors compared with PDS, GLS and CCA. TEAM can also achieve the best RMSEPs in most cases with a small number of calibration sets. TEAM is implemented in Python language and available as an open source package at https://github.com/zmzhang/TEAM. PMID- 26846328 TI - Ethanol extract of Pinus koraiensis leaves containing lambertianic acid exerts anti-obesity and hypolipidemic effects by activating adenosine monophosphate activated protein kinase (AMPK). AB - BACKGROUND: In this study, we investigated the anti-obesity and anti hyperlipidemic mechanisms of lambertianic acid (LA) isolated from Pinus koraiensis leaves and the ethanol extract of Pinus koraiensis leaves (EPK), both in vitro and in vivo. METHODS: Differentiated 3T3L-1 cells were treated with EPK (25 or 50 MUg/mL) or LA (200 MUM) and analyzed by western blotting or RT-PCR. In vitro, lipid accumulation of adipocytes was observed using Oil-Red-O staining and triglyceride analysis. The contribution of AMPK to anti-obesity activity was assessed by siRNA-mediated AMPK knockdown. After AMPK silencing, expression of AMPK was observed by western blotting. To confirm the in vitro activity, an animal study was conducted by administering a normal diet, HFD, and EPK for 6 weeks. Obesity-related physiological parameters and protein levels were measured. RESULTS: LA induced the expression of p-AMPK and inhibited PPARgamma, C/EBP alpha, adiponectin, FAS, SREBP-1, and HMGCR expression. EPK containing LA significantly decreased lipid accumulation and triglyceride levels in the differentiated 3 T3-L1 cells. EPK treatment suppressed the expression of adipogenic transcription factors, FABP, GPDH, and cholesterol-synthesis-related factors in the differentiated 3 T3-L1 cells. EPK increased the expression of p AMPK. The effects of EPK were reversed on inhibiting AMPK by using AMPK siRNA and compound C. In vivo analysis showed that body weight gain, serum triglyceride, total cholesterol, LDL cholesterol and AI value in the EPK treatment group were lower than those in the HFD control group. EPK induced the expression of p-AMPK and inhibited PPARgamma in liver and adipose tissue. CONCLUSIONS: Overall, the results suggest that EPK containing LA exerts significant anti-obesity and cholesterol-lowering effects by activating AMPK. PMID- 26846331 TI - Role(s) of TMA in polymerization. AB - Quenched-flow data for propene polymerization with rac-Me2Si(2-Me-4-Ph-1 indenyl)2ZrCl2/MAO support a picture where removal of MAO qualitatively changes the kinetic profile from a mainly enthalpic to a mainly entropic barrier. DFT studies suggest that a not previously recognized singly-bridged end-on coordination mode of Me6Al2 to catalytically active centers may be kinetically relevant as a resting state. In contrast, the more traditional doubly-bridged complex of Me3Al is proposed to be more relevant to chain transfer to cocatalyst. PMID- 26846330 TI - Structure of glycosylated NPC1 luminal domain C reveals insights into NPC2 and Ebola virus interactions. AB - Niemann-pick type C1 (NPC1) is an endo/lysosomal membrane protein involved in intracellular cholesterol trafficking, and its luminal domain C is an essential endosomal receptor for Ebola and Marburg viruses. We have determined the crystal structure of glycosylated NPC1 luminal domain C and find all seven possible sites are glycosylated. Mapping the disease mutations onto the glycosylated structure reveals a potential binding face for NPC2. Knowledge-based docking of NPC1 onto Ebola viral glycoprotein and sequence analysis of filovirus susceptible and refractory species reveals four critical residues, H418, Q421, F502 and F504, some or all of which are likely responsible for the species-specific susceptibility to the virus infection. PMID- 26846332 TI - The trilateral link between anaesthesia, perioperative visual loss and Flammer syndrome. AB - BACKGROUND: A variety of factors have been linked to perioperative visual loss during or directly after nonocular and ocular surgeries. Prolonged immobilization, biochemical factors and hemodynamic instability have been discussed as factors in the pathogenesis of this devastating complication. Perioperative visual loss in four consecutive patients, all featuring Flammer syndrome, is reported herein. To our knowledge, we present the first case series, which associates perioperative visual loss with Flammer syndrome. We assume that a low perfusion pressure, disturbed autoregulation of the ocular blood flow and altered drug sensitivity in such subjects, play significant role in the pathogenesis of this dreaded complication. CASES PRESENTATION: We analysed the medical records of four consecutive patients with permanent perioperative visual loss and complemented our findings with additional history taking and clinical examinations. A variety of tests was performed, including colour Doppler ultrasonography of the retroocular vessels, static and dynamic retinal vessel analysis. The visual loss was unilateral in three patients and bilateral in one. An extensive review of published perioperative vision loss cases was conducted. All four patients were male Caucasians, and exhibited prominent signs and symptoms of Flammer syndrome. The visual loss originated from a propensity for unstable ocular blood flow, combined with hyperreactivity toward pharmacological stimuli, leading together to disturbed autoregulation of the blood supply, and subsequently - to ocular hypoxia. An identified intrinsic hypoperfusion diathesis was a crucial pathophysiologic link in all of the patients. Other, yet unknown systemic or local factors may also be involved in this process. CONCLUSIONS: A review of numerous publications of perioperative visual loss and our data, support our hypothesis for a novel pathophysiologic model and incorporate Flammer syndrome as a distinct risk factor for paradoxical visual loss, during nonocular and ocular surgeries, or invasive procedures. To prevent the complications produced by disturbed blood flow autoregulation in such patients, guidelines for screening and tailored preoperative approach are given. PMID- 26846333 TI - Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study. AB - BACKGROUND: Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. STUDY DESIGN: Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. SETTING & PARTICIPANTS: Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. INTERVENTION: Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. OUTCOMES: Primary end point was Hb level response, defined as end-of-treatment Hb level change (DeltaHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level >= 11.0g/dL during the last 4 treatment weeks (part 2). MEASUREMENTS: Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). RESULTS: Baseline epoetin alfa doses were 138.3+/-51.3 (SD) and 136.3+/-47.7U/kg/wk in part 1 and 152.8+/ 80.6 and 173.4+/-83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ~1.7mg/kg. The least-squares-mean DeltaHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in DeltaHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised. LIMITATIONS: Short treatment duration and small sample size. CONCLUSIONS: In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels. PMID- 26846334 TI - Multiple Sclerosis Therapy With Disease-Modifying Treatments in Germany: The PEARL (ProspEctive phArmacoeconomic cohoRt evaluation) Noninterventional Study Protocol. AB - BACKGROUND: Patients with multiple sclerosis (MS) require long-term therapy and have a wide variety of needs for health-related support. The efficacy and safety of MS therapy, as assessed by both clinicians and patients, are important parameters that need to be considered. However, few studies combine data on efficacy and safety outcomes with pharmacoeconomic data. OBJECTIVE: Here, we present the study design of the ProspEctive phArmacoeconomic cohoRt evaluation (PEARL), a prospective, multicenter, noninterventional cohort study on patients with relapsing-remitting MS (RRMS) treated with disease-modifying treatments (DMTs). METHODS: During a prospective observational phase of 24 months per patient, PEARL evaluated clinical and patient-perceived efficacy and safety measures, as well as pharmacoeconomic data on RRMS patients treated with DMTs interferon beta and glatiramer acetate. Measurements of the patients' perceptions included the assessment of patient-reported quality of life, treatment satisfaction, and compliance. The study was planned to include 1800 outpatients from 180 German neurological practices who had continuously been treated with an approved DMT for at least 30 days. The primary statistical analyses of the PEARL study will be descriptive. Particular focus will be on specific subgroups, such as patients who switched DMTs during therapy and patients with disease worsening or disease activity. Subgroups will be compared using stratified analyses. RESULTS: Data collection for PEARL started in September 2010 and ended in July 2013. As of July 2015, the study is completed and is currently being analyzed and written up. CONCLUSIONS: PEARL is evaluating both the health status and resource utilization of RRMS patients treated with DMTs in Germany. The combination of pharmacoeconomic data with clinical and patients' self-perceived efficacy and safety outcomes will add useful information to the currently incomplete picture of the overall RRMS burden in Germany. PMID- 26846336 TI - Characteristics of the Spanish- and English-Language Self-Efficacy to Manage Diabetes Scales. AB - PURPOSE: The purpose of this study was to examine the characteristics of the Spanish-language diabetes self-efficacy scale (DSES-S) and the English-language version (DSES). METHODS: This study consists of secondary data from 3 randomized studies that administered the DSES-S and DSES at 2 time points. The scales consist of 8 Likert-type 10-point items. Principal component analysis was applied to determine if the scales were unitary or consisted of subscales. Univariate statistics were used to describe the scales. Sensitivity to change was measured by comparing randomized treatment with control groups, where the treatment included methods designed to enhance self-efficacy. General linear models were used to examine the association between the scales and the 8 medical outcomes after controlling for demographic variables. RESULTS: Principal component analysis indicated that there were 2 subscales for both versions: self-efficacy for behaviors and self-efficacy to manage blood levels and medical condition. The measures had similar means across the 3 studies, high internal consistent reliability, values distributed across the entire range, and they showed no evidence of floor effects and little evidence of ceiling effects. The measures were sensitive to change. They were associated with several health indicators and behaviors at baseline, and changes were associated with changes in health measures. CONCLUSIONS: The self-efficacy measures behaved consistently across the 3 studies and were highly reliable. Associations with medical indicators and behaviors suggested validity, although further study would be desirable to compare other measures of self-efficacy for people with type 2 diabetes. These brief scales are appropriate for measuring self-efficacy to manage diabetes. PMID- 26846335 TI - Pirfenidone and nintedanib modulate properties of fibroblasts and myofibroblasts in idiopathic pulmonary fibrosis. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an incurable lung disease with a poor prognosis. Fibroblasts and myofibroblasts are the key cells in the fibrotic process. Recently two drugs, pirfenidone and nintedanib, were approved for clinical use as they are able to slow down the disease progression. The mechanisms by which these two drugs act in in vitro cell systems are not known. The aim of this study was therefore to examine the effects of pirfenidone and nintedanib on fibroblasts and myofibroblasts structure and function established from patients with or without IPF. METHODS: Stromal cells were collected and cultured from control lung (n = 4) or IPF (n = 7). The cells were treated with pirfenidone and/or nintedanib and the effect of treatment was evaluated by measuring cell proliferation, alpha smooth muscle actin (alpha-SMA) and fibronectin expression by Western analysis and/or immunoelectron microscopy, ultrastructural properties by transmission electron microscopy and functional properties by collagen gel contraction and invasion assays. RESULTS: Both pirfenidone and nintedanib reduced in vitro proliferation of fibroblastic cells in a dose dependent manner. The number of cells from control lung was reduced to 47 % (p = 0.04) and of IPF cells to 42 % (p = 0.04) by 1 mM pirfenidone and correspondingly to 67 % (p = 0.04) and 68 % (p = 0.04), by 1 MUM nintedanib. If both drugs were used together, a further reduced proliferation was observed. Both pirfenidone and nintedanib were able to reduce the amount of alpha-SMA and the myofibroblastic appearance although the level of reduction was cell line dependent. In functional assays, the effect of both drugs was also variable. CONCLUSIONS: We conclude that the ultrastructure and function of fibroblasts and myofibroblasts are affected by pirfenidone and nintedanib. Combination of the drugs reduced cell proliferation more than either of them individually. Human lung derived cell culture systems represent a potential platform for screening and testing drugs for fibrotic diseases. PMID- 26846337 TI - Robust functional clustering of ERP data with application to a study of implicit learning in autism. AB - Motivated by a study on visual implicit learning in young children with Autism Spectrum Disorder (ASD), we propose a robust functional clustering (RFC) algorithm to identify subgroups within electroencephalography (EEG) data. The proposed RFC is an iterative algorithm based on functional principal component analysis, where cluster membership is updated via predictions of the functional trajectories obtained through a non-parametric random effects model. We consider functional data resulting from event-related potential (ERP) waveforms representing EEG time-locked to stimuli over the course of an implicit learning experiment, after applying a previously proposed meta-preprocessing step. This meta-preprocessing is designed to increase the low signal-to-noise ratio in the raw data and to mitigate the longitudinal changes in the ERP waveforms which characterize the nature and speed of learning. The resulting functional ERP components (peak amplitudes and latencies) inherently exhibit covariance heterogeneity due to low data quality over some stimuli inducing the averaging of different numbers of waveforms in sliding windows of the meta-preprocessing step. The proposed RFC algorithm incorporates this known covariance heterogeneity into the clustering algorithm, improving cluster quality, as illustrated in the data application and extensive simulation studies. ASD is a heterogeneous syndrome and identifying subgroups within ASD children is of interest for understanding the diverse nature of this complex disorder. Applications to the implicit learning paradigm identify subgroups within ASD and typically developing children with diverse learning patterns over the course of the experiment, which may inform clinical stratification of ASD. PMID- 26846338 TI - Consecutive bilateral decompression retinopathy after mitomycin C trabeculectomy: a case report. AB - BACKGROUND: After a successful trabeculectomy, a sudden intraocular pressure decrease may alter the intracranial to intraocular pressure ratio and cause decompression retinopathy. Frequent Valsalva maneuvers may also play a role in its pathogenesis. This condition may manifest as multiple retinal hemorrhages, edema of the optic disc, macular edema, or a sudden decrease in visual acuity postoperatively. Outcomes for patients are usually good, with spontaneous resolution occurring within a matter of weeks. It has been rarely reported in the literature as a bilateral condition. CASE PRESENTATION: We present a case of consecutive bilateral decompression retinopathy in a 54-year-old severely obese Caucasian woman (body mass index 37 kg/m(2)) with open angle glaucoma and a poor history of medical therapeutic compliance, who chose surgical treatment based on her inability to consistently use ocular drops. Our patient underwent a trabeculectomy with mitomycin C in both eyes, with surgeries taking place 3 months apart. After the first surgery, 2 weeks postoperatively, she complained of decreased visual acuity. Examination of her right eye fundus revealed multiple retinal hemorrhages and disc edema. There was a similar pattern in her left eye, this time including maculopathy. Her visual acuity and fundoscopic changes resolved spontaneously over a period of a month in both cases. Currently, our patient has well-controlled bilateral intraocular pressure, ranging between 14 and 16 mmHg, without hypotensive medication. CONCLUSIONS: Decompression retinopathy is a potential complication after glaucoma surgery, but has rarely been described as a bilateral consecutive condition. A comprehensive approach could help to anticipate its occurrence and manage it. PMID- 26846339 TI - DLC-1 is an independent prognostic marker and potential therapeutic target in hepatocellular cancer. AB - BACKGROUND: The 5-year survival rate of patients with hepatocellular cancer (HCC) was very low because of invasion and metastasis in the early stage. Biomarkers might help predict early occurrence of invasion and metastasis. Accumulating evidence has shown that deleted in liver cancer-1 (DLC1) may be considered as a metastasis suppressor gene in numerous solid and hematological cancers. However, its prognostic role and mechanisms that regulate and coordinate these activities remain poorly understood. METHODS: With the method of immunohistochemistry, the expression of DLC-1 as well as Rho A, ROCK2, moesin had been characterized in 80 HCC tissues and adjacent noncancerous tissues. The correlation between their expression and their relationships with clinicopathological characteristics of HCC were also investigated. In addition, the prognostic value of DLC1 expression within the tumor tissues was assessed by Cox regression and Kaplan-Meier analysis. RESULTS: DLC1 expression was significantly lower in HCC tissues than in adjacent noncancerous tissues, and DLC-1 expression was found to be negatively correlated with tumor differentiation, TNM stage and lymph node metastasis. Furthermore, DLC-1 expression was found to inversely correlate with Rho A, ROCK2 and moesin which were all highly expressed in HCC tissues. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in HCC patients with higher DLC1 expression, compared to those with lower expression of DLC1. Multivariate Cox proportional hazard analyses revealed that DLC1 was an independent factor affecting the overall survival probability. CONCLUSION: DLC1 could be served as a tumor suppressor gene in the progression especially in the invasion and metastasis of HCC. DLC1 perhaps played its role by regulating the expression of Rho A, ROCK2 and moesin. Evaluation of the expression of DLC-1 might be a good prognostic marker for patients with HCC. PMID- 26846341 TI - Validation of the Breast Cancer Screening Beliefs Questionnaire among African Australian women. AB - BACKGROUND: The Breast Cancer Screening Beliefs Questionnaire (BCSBQ) has been designed as a culturally appropriate instrument for assessing women's beliefs, knowledge and attitudes to breast cancer and breast cancer screening practices. While it has proved to be a reliable instrument when applied to women of Chinese, Arabic and Korean origin living in Australia, its psychometric properties among women from African backgrounds have not been tested. The aim of this study is to examine the psychometric properties of the BCSBQ among African Australian women. METHODS: The BCSBQ was administered to 284 African Australian women who were recruited from a number of African community organizations and churches. Factor analysis was conducted to study the factor structure. Construct validity was examined using Cuzick's non-parametric test while Cronbach alpha was used to assess internal consistency reliability. RESULTS: Exploratory factor analysis results demonstrated that the African-Australian BCSBQ can be conceptualized as a 4-factor model. The third factor, viz. "barriers to mammography", was split into two separate factors namely, "psychological" and "practical" barriers. The results indicated that the African-Australian BCSBQ had both satisfactory validity and internal consistency. The Cronbach's alpha of the three subscales ranged between 0.84-0.92. The frequency of breast cancer screening practices (breast awareness, clinical breast-examination and mammography) were significantly associated with attitudes towards general health check-ups and perceived barriers to mammographic screening. CONCLUSIONS: Our study provided evidence to support the psychometric properties of the BCSBQ.in African Australian women. The study moreover demonstrated that the use of the instrument can help health professionals to understand the beliefs, knowledge and attitudes to breast cancer among African Australian women and also the factors that impact on their breast cancer screening practices. PMID- 26846342 TI - Exploration of multiple Sortase A protein conformations in virtual screening. AB - Methicillin resistant Staphylococcus aureus (MRSA) has become a major health concern which has brought about an urgent need for new therapeutic agents. As the S. aureus Sortase A (SrtA) enzyme contributes to the adherence of the bacteria to the host cells, inhibition thereof by small molecules could be employed as potential antivirulence agents, also towards resistant strains. Albeit several virtual docking SrtA campaigns have been reported, no strongly inhibitatory non covalent binders have as yet emerged therefrom. In order to better understand the binding modes of small molecules, and the effect of different receptor structures employed in the screening, we herein report on an exploratory study employing 10 known binders and 500 decoys on 100 SrtA structures generated from regular or steered molecular dynamics simulations on four different SrtA crystal/NMR structures. The results suggest a correlation between the protein structural flexibility and the virtual screening performance, and confirm the noted immobilization of the beta6/beta7 loop upon substrate binding. The NMR structures reported appear to perform slightly better than the Xray-crystal structures, but the binding modes fluctuate tremendously, and it might be suspected that the catalytic site is not necessarily the preferred site of binding for some of the reported active compounds. PMID- 26846343 TI - One Hundred Planned Robotic Segmentectomies: Early Results, Technical Details, and Preferred Port Placement. AB - BACKGROUND: Both robotic pulmonary operations and anatomic segmentectomy are being increasingly performed. The largest published series of anatomic robotic segmentectomy comprises 35 patients, and the specific details of port placement are poorly understood. METHODS: This is a review of a consecutive series of patients from a single surgeon's prospective database. All patients in the study were scheduled to undergo robotic anatomic segmentectomy. RESULTS: Between February 2010 and December 2014, 100 patients went to the operating room for a planned pulmonary segmentectomy. A robotic approach was chosen for all. Seven patients underwent conversion to robotic lobectomy, and the remaining 93 patients had an anatomic robotic segmentectomy. There were no conversions to thoracotomy. Indications for resection were lung cancer in 79 patients, metastatic lesions in 10 patients, fungal infections in 4 patients, and other conditions in 7 patients. The median age was 69 years, and 50 patients were men. The median blood loss was 20 mL (range, 10-120 mL), the median number of lymph nodes removed was 19, the median operative time was 1.28 hours (88 minutes), the median length of stay was 3 days, and major morbidity occurred in 2 patients (pneumonia in both). All had undergone R0 resection. There were no 30- or 90-day mortalities. Of the 79 patients with lung cancer, the median follow-up was 30 months, and 3 patients (3.4%) had recurrence in the operated lobe. Overall survival was 95% at 30 months. CONCLUSIONS: Completely portal robotic anatomic segmentectomy is safe and effective and offers outstanding intraoperative 30-day and 90-day results. The recurrence rate is approximately 3% at 2.5 years. PMID- 26846345 TI - Diabetes: Stress resilience and risk of type 2 diabetes mellitus. PMID- 26846344 TI - Comparative Phosphoproteomics Analysis of VEGF and Angiopoietin-1 Signaling Reveals ZO-1 as a Critical Regulator of Endothelial Cell Proliferation. AB - VEGF and angiopoietin-1 (Ang-1) are essential factors to promote angiogenesis through regulation of a plethora of signaling events in endothelial cells (ECs). Although pathways activated by VEGF and Ang-1 are being established, the unique signaling nodes conferring specific responses to each factor remain poorly defined. Thus, we conducted a large-scale comparative phosphoproteomic analysis of signaling pathways activated by VEGF and Ang-1 in ECs using mass spectrometry. Analysis of VEGF and Ang-1 networks of regulated phosphoproteins revealed that the junctional proteins ZO-1, ZO-2, JUP and p120-catenin are part of a cluster of proteins phosphorylated following VEGF stimulation that are linked to MAPK1 activation. Down-regulation of these junctional proteins led to MAPK1 activation and accordingly, increased proliferation of ECs stimulated specifically by VEGF, but not by Ang-1. We identified ZO-1 as the central regulator of this effect and showed that modulation of cellular ZO-1 levels is necessary for EC proliferation during vascular development of the mouse postnatal retina. In conclusion, we uncovered ZO-1 as part of a signaling node activated by VEGF, but not Ang-1, that specifically modulates EC proliferation during angiogenesis. PMID- 26846346 TI - Epigenetics: On-off switch for obesity. PMID- 26846348 TI - Diabetes: New TREG gene signature for T1DM. PMID- 26846347 TI - Diabetes: Encapsulated beta-cell implants enable glycaemic control. PMID- 26846350 TI - Gray matter correlates of dopaminergic degeneration in Parkinson's disease: A hybrid PET/MR study using (18) F-FP-CIT. AB - Dopaminergic degeneration is a hallmark of Parkinson's disease (PD), which causes various symptoms affected by corticostriatal circuits. So far, the relationship between cortical changes and dopamine loss in the striatum is unclear. Here, we evaluate the gray matter (GM) changes in accordance with striatal dopaminergic degeneration in PD using hybrid PET/MR. Sixteen patients with idiopathic PD underwent (18) F-FP-CIT PET/MR. To measure dopaminergic degeneration in PD, binding ratio (BR) of dopamine transporter in striatum was evaluated by (18) F-FP CIT. Voxel-based morphometry (VBM) was used to evaluate GM density. We obtained voxelwise correlation maps of GM density according to the striatal BR. Voxel-by voxel correlation between BR maps and GM density maps was done to evaluate region specific correlation of striatal dopaminergic degeneration. There was a trend of positive correlation between striatal BR and GM density in the cerebellum, parahippocampal gyri, and frontal cortex. A trend of negative correlation between striatal BR and GM density in the medial occipital cortex was found. Voxel-by voxel correlation revealed that the positive correlation was mainly dependent on anterior striatal BR, while posterior striatal BR mostly showed negative correlation with GM density in occipital and temporal cortices. Decreased GM density related to anterior striatal dopaminergic degeneration might demonstrate degeneration of dopaminergic nonmotor circuits. Furthermore, the negative correlation could be related to the motor circuits of posterior striatum. Our integrated PET/MR study suggests that the widespread structural progressive changes in PD could denote the cortical functional correlates of the degeneration of striatal dopaminergic circuits. Hum Brain Mapp 37:1710-1721, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26846351 TI - National epidemiology of carbapenem-resistant and extensively drug-resistant Gram negative bacteria isolated from blood samples in China in 2013. AB - Although antimicrobial resistance poses a great challenge to clinicians in China, there are limited antimicrobial resistance data on Gram-negative bacteria nationwide. We investigated the phenotypic characteristics of carbapenem resistant Escherichia coli (CREC) and Klebsiella pneumoniae (CRKP) as well as extensively drug-resistant strains of Pseudomonas aeruginosa (XDRPA) and Acinetobacter baumannii (XDRAB) isolated from blood cultures in China. Data were collected on 24113 isolates from the China surveillance of antimicrobial resistance program in 2013, which comprised 208 hospitals located in all seven administrative regions of China. Minimum inhibitory concentrations (MICs) for common antimicrobials were determined by commercial automated systems available at local hospitals, and associations with geographic and clinical distributions was further studied. The overall prevalence of CREC, CRKP, XDRAB and XDRPA strains was 1.0, 5.5, 13.7 and 4.2%, respectively. Except for CREC, which did not differ greatly by region, the prevalence of the remaining three strains varied significantly across regions. The highest prevalence of CRKP (10.6%) and XDRAB (13.1%) were found in the pediatric group, and higher prevalence of all four target strains was found in the intensive care unit. For imipenem, 55.8% of CREC and 22.9% of CRKP strains had MICs of <=4 MUg/mL, while 97.4% XDRAB and 84% XDRPA isolates had MICs of >=16 MUg/mL. All CREC, CRKP and 81.2% of XDRAB strains were susceptible to tigecycline, with MIC90 values of 0.5, 2 and 4 MUg/mL, respectively. In conclusion, a high prevalence of CRKP and XDRAB has emerged in China, especially in children and in the intensive care unit. PMID- 26846349 TI - Discovery of a novel inhibitor of kinesin-like protein KIFC1. AB - Historically, drugs used in the treatment of cancers also tend to cause damage to healthy cells while affecting cancer cells. Therefore, the identification of novel agents that act specifically against cancer cells remains a high priority in the search for new therapies. In contrast with normal cells, most cancer cells contain multiple centrosomes which are associated with genome instability and tumorigenesis. Cancer cells can avoid multipolar mitosis, which can cause cell death, by clustering the extra centrosomes into two spindle poles, thereby enabling bipolar division. Kinesin-like protein KIFC1 plays a critical role in centrosome clustering in cancer cells, but is not essential for normal cells. Therefore, targeting KIFC1 may provide novel insight into selective killing of cancer cells. In the present study, we identified a small-molecule KIFC1 inhibitor, SR31527, which inhibited microtubule (MT)-stimulated KIFC1 ATPase activity with an IC50 value of 6.6 MUM. By using bio layer interferometry technology, we further demonstrated that SR31527 bound directly to KIFC1 with high affinity (Kd=25.4 nM). Our results from computational modelling and saturation-transfer difference (STD)-NMR experiments suggest that SR31527 bound to a novel allosteric site of KIFC1 that appears suitable for developing selective inhibitors of KIFC1. Importantly, SR31527 prevented bipolar clustering of extra centrosomes in triple negative breast cancer (TNBC) cells and significantly reduced TNBC cell colony formation and viability, but was less toxic to normal fibroblasts. Therefore, SR31527 provides a valuable tool for studying the biological function of KIFC1 and serves as a potential lead for the development of novel therapeutic agents for breast cancer treatment. PMID- 26846352 TI - Peptide nanostructures in biomedical technology. AB - Nanostructures of peptides have been investigated for biomedical applications due to their unique mechanical and electrical properties in addition to their excellent biocompatibility. Peptides may form fibrils, spheres and tubes in nanoscale depending on the formation conditions. These peptide nanostructures can be used in electrical, medical, dental, and environmental applications. Applications of these nanostructures include, but are not limited to, electronic devices, biosensing, medical imaging and diagnosis, drug delivery, tissue engineering and stem cell research. This review offers a discussion of basic synthesis methods, properties and application of these nanomaterials. The review concludes with recommendations and future directions for peptide nanostructures. WIREs Nanomed Nanobiotechnol 2016, 8:730-743. doi: 10.1002/wnan.1393 For further resources related to this article, please visit the WIREs website. PMID- 26846353 TI - Clinical outcomes of whole pelvis radiotherapy and stereotactic body radiotherapy boost for intermediate- and high-risk prostate cancer. AB - AIM: We report our experience with Cyberknife to deliver hypofractionated stereotactic body radiotherapy (SBRT) boost combined with whole pelvis radiotherapy (WPRT) to patients with intermediate- to high-risk prostate cancer. METHODS: From March 2008 to July 2014, 39 patients with newly diagnosed, intermediate- and high-risk (National Comprehensive Cancer Network definition) localized prostate cancer were treated with WPRT and SBRT boost. The whole pelvis dose was 45 Gy (25 fractions of 1.8 Gy) and the SBRT boost dose was 21 Gy (3 fractions of 7 Gy). No one received androgen deprivation therapy before biochemical relapse. The acute and late toxicities were recorded using the Radiation Therapy Oncology Group scale. Prostate-specific antigen (PSA) response was monitored. RESULTS: Thirty-nine patients with a median 53.6 months (range 14 74 months) follow-up were analyzed. The median pretreatment PSA was 15.97 ng/mL. The estimated 5-year biochemical failure (BCF)-free survival was 94.7%. Two BCFs were observed in only high-risk group. The median PSA nadir was 0.30 ng/mL at median 36 months and PSA bounce occurred in 15.4% (n = 6) of patients at median 12 months. No grade 3 acute toxicity was noted. A total of 23% of the patients had grade 2 acute genitourinary (GU) toxicities and 21% had grade 2 acute gastrointestinal (GI) toxicities. At 2 months, most complications had returned to baseline. GU and GI toxicities were observed. CONCLUSIONS: WPRT followed by SBRT boost using Cyberknife in intermediate- and high-risk prostate cancer is feasible with minimal toxicity and encouraging BCF-free survival. PMID- 26846354 TI - Proteomic analysis reveals the differential histone programs between male germline cells and vegetative cells in Lilium davidii. AB - In flowering plants, male germline fate is determined after asymmetric division of the haploid microspore. Daughter cells have distinct fates: the generative cell (GC) undergoes further mitosis to generate sperm cells (SCs), and the vegetative cell (VC) terminally differentiates. However, our understanding of the mechanisms underlying germline development remains limited. Histone variants and modifications define chromatin states, and contribute to establishing and maintaining cell identities by affecting gene expression. Here, we constructed a lily protein database, then extracted and detailed histone entries into a comprehensive lily histone database. We isolated large amounts of nuclei from VCs, GCs and SCs from lily, and profiled histone variants of all five histone families in all three cell types using proteomics approaches. We revealed 92 identities representing 32 histone variants: six for H1, 11 for H2A, eight for H2B, five for H3 and two for H4. Nine variants, including five H1, two H2B, one H3 and one H4 variant, specifically accumulated in GCs and SCs. We also detected H3 modification patterns in the three cell types. GCs and SCs had almost identical histone profiles and similar H3 modification patterns, which were significantly different from those of VCs. Our study also revealed the presence of multiple isoforms, and differential expression patterns between isoforms of a variant. The results suggest that differential histone programs between the germline and companion VCs may be established following the asymmetric division, and are important for identity establishment and differentiation of the male germline as well as the VC. PMID- 26846355 TI - Late Manifestation of Coronary Sinus and Left Atrial Perforation of a Left Ventricular Pacemaker Lead at Extraction. AB - A 56-year-old man presented for lead extraction of a left ventricular (LV) lead that had been deactivated due to hiccups and of a right ventricular (RV) lead with a high threshold. Pus was noted upon entering the pocket. The right atrial and RV leads were extracted, but traction on the LV lead caused ischemia and was not performed. An echocardiogram demonstrated the lead in the left atrium and a robotic-assisted thoracotomy was used to remove the lead that had unroofed the coronary sinus, gone into the left atrium, and perforated through the free wall into the pericardium. PMID- 26846356 TI - Perioperative prophylaxis to prevent recurrence following cataract surgery in uveitic patients: a two-centre, prospective, randomized trial. AB - PURPOSE: To compare the postoperative risk of inflammatory relapse in two groups of uveitic patients who underwent cataract surgery: one group had perioperative topical steroids alone and the other used topical and oral steroids. METHODS: Prospective, randomized, unmasked, duocentric clinical trial conducted at the University of Parma (Italy), and the Jules Gonin Eye Hospital of Lausanne (Switzerland). Patients with a history of non-infectious uveitis requiring cataract surgery in 2009-2013 were assigned to two groups of perioperative prophylaxis: (A) intensive topical steroids alone; (B) the same topical regimen combined with oral steroids. Uveitis relapse over a period of 6 months was assessed. RESULTS: In total, 52 eyes in 50 patients were randomized: 28 eyes were assigned to group A (topical) and 24 eyes to group B (topical + oral). Mean relapse-free survival time was 131 +/- 11 days in group A and 150 +/- 13 days in group B. This difference was not statistically significant (p = 0.42). At the end of follow-up, the groups were also comparable in terms of significant improvement in visual acuity (p < 0.01), mean central macular thickness (CMT) and IOP variation. CONCLUSIONS: Absolute and long-lasting control of ocular, and possibly systemic, inflammation predisposes uveitis patients to satisfactory results after cataract extraction and intraocular lens implantation. Despite a lower rate of recurrences following oral steroid supplementation, the efficacy of an intensive perioperative topical steroid regimen alone in preventing postoperative uveitis relapse was statistically comparable. Secondary outcomes were also comparable between the two groups. Transient IOP elevation should be expected until treatment discontinuation. PMID- 26846358 TI - Spinal aneurysmal bone cyst presenting as acute paraparesis during pregnancy. AB - Aneurysmal bone cysts (ABC) are benign but locally aggressive osseous lesions characterized by blood-filled cystic cavities that account for 1-2% of all bone tumors. While pain remains the most common presenting symptom of spinal ABC, extensive anterior column involvement can result in vertebral fractures, spinal instability, and neurological deficits from compression of neural elements. An exceedingly rare case of thoracic ABC presenting as acute paraparesis in a 21 year-old pregnant woman, that was successfully treated with urgent surgical decompression and stabilization, is reported, with discussion of management strategies and review of the pertinent literature. PMID- 26846357 TI - National Safety Associates nutritional supplementation trial of fruit and vegetable extracts and vascular function (NNTV): study protocol for a randomised controlled trial. AB - BACKGROUND: Cardiovascular disease has a multifactorial aetiology with a number of both modifiable and non-modifiable risk factors. Although evidence indicates that dietary intake plays an important role, few studies have focused on the effect of fruit and vegetable consumption on early markers of vascular function. Therefore, we hypothesised that supplementation with capsules containing a combination of fruit and vegetable extracts over 12 weeks can significantly modulate biomarkers of vascular function compared with a control group receiving placebo. METHODS/DESIGN: This is a double-blind, randomised controlled trial that includes overweight and obese but otherwise healthy participants. Participants are randomly allocated to one of two groups: active supplementation (encapsulated fruit and vegetable powder) or placebo taken twice daily for 12 weeks, whereas both groups will be given the '5-A-Day' dietary advice. The primary outcome is to measure changes to the carotid intima media thickness (cIMT) between the two groups from baseline (test visit 1) to 12 weeks later (test visit 2). The secondary outcomes include macro- and microvascular changes and changes to blood markers. DISCUSSION: In addition to the primary and secondary objectives, this explanatory trial incorporates potential novel biomarkers such as trimethylamine N-oxide (TMAO) and lipopolysaccharide (LPS). TRIAL REGISTRATION: ISRCTN14315618. Registration date 27 February 2014. PMID- 26846359 TI - Enantioselective Formal Syntheses of 11 Nuphar Alkaloids and Discovery of Potent Apoptotic Monomeric Analogues. AB - Concise, scalable, and enantioselective formal syntheses of eight dimeric and three monomeric nuphar alkaloids were achieved, along with the construction of a stereochemically diverse collection of the first known monomeric analogues having apoptotic activity. The syntheses involved the development of highly enantioselective Bronsted acid catalyzed vinylogous Mukaiyama-Mannich reactions, which feature the unprecedented use of a supersilyl group to control the regio-, enantio- and diastereoselectivity. Biological studies reveal that several of these novel nuphar analogues are even more potent than their dimeric natural product counterparts. PMID- 26846361 TI - Comparative Efficacy and Safety of Nine Anti-Platelet Therapies for Patients with Ischemic Stroke or Transient Ischemic Attack: a Mixed Treatment Comparisons. AB - Anti-platelet treatments, an effective anti-thrombotic therapy, are widely used in non-cardioembolic ischemic stroke or transient ischemic attack (TIA), including aspirin, cilostazol, clopidogrel, and other mono or dual therapies, while the optimal choice remains uncertain. All the literatures of 38 eligible randomized control trials were searched in PubMed, Embase, and China National Knowledge Internet (CNKI) without language limitation. And, nine anti-platelet therapies were assessed, including aspirin, clopidogrel, cilostazol, ticlopidine, triflusal, terutroban, sarpogrelate, dipyridamole plus aspirin, and clopidogrel plus aspirin. Additionally, we extract data of composite vascular events, major bleeding, ischemic stroke, intracranial hemorrhage, and all-cause death, as indicators of efficacy and safety. And among them, composite vascular events were the primary outcome. The binary outcomes were expressed as odds ratios (ORs) with corresponding 95 % confidence intervals (CIs). Both traditional meta-analysis and network meta-analysis were performed. Besides, for each outcome, the rank order was applied to reflect the superiority of every therapy compared with others, using the surface under the cumulative ranking curve (SUCRA). A cluster analysis was also conducted. Through the network meta-analysis, the synthesized data shows that cilostazol performed best on composite vascular events compared with placebo (OR = 0.62, 95 % CI 0.46-0.83) and aspirin (OR = 0.71, 95 % CI 0.53-0.95). In terms of ischemic stroke, clopidogrel plus aspirin seems the optimal, and it has significant difference between placebo (OR = 0.53, 95 % CI 0.35-0.74) and aspirin (OR = 0.75, 95 % CI 0.61-0.95). Meanwhile, cilostazol is also the first rank in major bleeding, especially when it is in contrast to aspirin (OR = 0.13, 95 % CI 0.02-0.70) and clopidogrel plus aspirin (OR = 0.09, 95 % CI 0.01-0.50). There is no significant difference among these nine treatments and placebo, as to all cause death and intracranial hemorrhage. According to the cluster analysis, cilostazol can be the best choice with comprehensive assessment of composite vascular events, ischemic stroke and major bleeding. Based on this network meta analysis, cilostazol was recommended as the optimal choice with good performance in both efficacy and safety for patient with ischemic stroke or TIA among nine anti-platelet therapies. PMID- 26846360 TI - Nrf2 Weaves an Elaborate Network of Neuroprotection Against Stroke. AB - Nuclear factor erythroid 2-related factor 2 (Nrf2) is a neuroprotective transcription factor that has recently attracted increased attention. Stroke, a common and serious neurological disease, is currently a leading cause of death in the USA so far. It is therefore of vital importance to explore how Nrf2 behaves in stroke. In this review, we first introduce the structural features of Nrf2 and Kelch-like ECH-associated protein 1 (Keap1) and briefly depict the activation, inactivation, and regulation processes of the Nrf2 pathway. Next, we discuss the physiopathological mechanisms, upstream modulators, and downstream targets of the Nrf2 pathway. Following this background, we expand our discussion to the roles of Nrf2 in ischemic and hemorrhagic stroke and provide several potential future directions. The information presented here may be useful in the design of future experimental research and increase the likelihood of using Nrf2 as a therapeutic target for stroke in the future. PMID- 26846362 TI - Liver X Receptor beta Is Involved in Formalin-Induced Spontaneous Pain. AB - Increasing evidence indicates that the liver X receptor(LXR) beta modulates inflammatory pain. However, the molecular mechanisms through which LXRbeta modulates pain are unclear. Here, we found that LXRbeta-null mice responded more strongly to acute noxious stimuli than wild-type (WT) littermates (in the hot plate and Hargreaves tests) and had augmented tonic inflammatory pain (in the formalin test). This increased reactivity to inflammatory pain was accompanied by enhanced formalin-evoked Fos and pERK staining of second-order nociceptive neurons. Immunohistochemistry showed that the expression of CGRP, SP, and IB4 was increased in the lamina I-II of the lumbar dorsal horns in formalin-injected LXRbeta knockout (KO) mice compared with the WT controls. In addition, LXRbeta deletion in the mice enhanced the formalin-induced inflammation with more activated microglia and astrocytes in the spinal cord. Furthermore, the levels of pro-inflammatory cytokines (IL-1beta ,TNF-alpha) as well as NFkappaB in the formalin-injected paw were elevated by the loss of LXRbeta. Taken together, these data indicate that LXRbeta is involved in acute as well as inflammatory pain, and thus, it may be considered as a new target for the development of analgesics. PMID- 26846365 TI - Erratum to: Differences in Varroa destructor infestation rates of two indigenous subspecies of Apis mellifera in the Republic of South Africa. PMID- 26846363 TI - The Next Generation of Biomarker Research in Spinal Cord Injury. AB - In traumatic spinal cord injury (SCI) patients, the assessment of the exact degree of lesion severity and neurological prognosis has proven to be extremely challenging. The current tools for predicting functional outcome in SCI patients such as clinical examination and magnetic resonance imaging are often inaccessible to unstable or polytraumatized patients, lack sensitivity, and are unreliable in the acute phase of the injury. Multiple candidate protein biomarkers known to be linked to the pathology have been studied for their potential to predict neurological outcome over time. This hypothesis-driven approach, however, has yielded only minimal success, and the reported individual markers lack sensitivity and correlation with specific outcome measures, which highlights the need for an unbiased high-throughput screening approach to identify novel candidate biomarkers. Antibodies were suggested to represent better biomarkers as their counterpart antigens, as they are highly specific and abundantly present in blood due to their inherent amplification and long half life. Moreover, antibodies are easily accessible and are amenable to high throughput screening. We therefore suggest an unbiased, high-throughput, and powerful antibody profiling procedure, named Serological antigen selection, based on complementary DNA (cDNA) phage display to combine the multiple benefits of stable and frequent antibodies and those of an unbiased method. The application of such an innovative and unbiased approach can complement the more traditional approaches to aid in the discovery of novel SCI-associated biomarkers. PMID- 26846364 TI - Lower Serum Zinc and Higher CRP Strongly Predict Prenatal Depression and Physio somatic Symptoms, Which All Together Predict Postnatal Depressive Symptoms. AB - Pregnancy and delivery are associated with activation of immune-inflammatory pathways which may prime parturients to develop postnatal depression. There are, however, few data on the associations between immune-inflammatory pathways and prenatal depression and physio-somatic symptoms. This study examined the associations between serum zinc, C-reactive protein (CRP), and haptoglobin at the end of term and prenatal physio-somatic symptoms (fatigue, back pain, muscle pain, dyspepsia, obstipation) and prenatal and postnatal depressive and anxiety symptoms as measured using the Edinburgh Postnatal Depression Scale (EPDS), Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), and Spielberger's State Anxiety Inventory (STAI). Zinc and haptoglobin were significantly lower and CRP increased at the end of term as compared with non pregnant women. Prenatal depression was predicted by lower zinc and lifetime history of depression, anxiety, and premenstrual tension syndrome (PMS). The latter histories were also significantly and inversely related to lower zinc. The severity of prenatal EDPS, HAMD, BDI, STAI, and physio-somatic symptoms was predicted by fatigue in the first and second trimesters, a positive life history of depression, anxiety, and PMS, and lower zinc and higher CRP. Postnatal depressive symptoms are predicted by prenatal depression, physio-somatic symptoms, zinc and CRP. Prenatal depressive and physio-somatic symptoms have an immune-inflammatory pathophysiology, while postnatal depressive symptoms are highly predicted by prenatal immune activation, prenatal depression, and a lifetime history of depression and PMS. Previous episodes of depression, anxiety disorders, and PMS may prime pregnant females to develop prenatal and postnatal depressive symptoms via activated immune pathways. PMID- 26846366 TI - Choosing exercise or pharmacologic stress imaging, or exercise ECG testing alone: How to decide. PMID- 26846367 TI - Accuracy of myocardial perfusion imaging in detecting multivessel coronary artery disease: A cardiac CZT study. AB - BACKGROUND: Myocardial perfusion imaging (MPI) performed on traditional single photon emission computed-tomography cameras has been shown to have a sub-optimal accuracy in detecting multivessel coronary artery disease (CAD). METHODS: Six hundred and ninety-five patients were submitted to MPI on a novel cadmium-zinc telluride (CZT) camera and coronary angiography. A coronary stenosis >70% was considered obstructive. In every patient, the summed stress score (SSS) was computed. Moreover, the regional stress scores were also calculated for every coronary territory. RESULTS: Four-hundred and forty-one patients had obstructive CAD in one (28%), two (19%), or three (17%) vessels. At per-patient analysis, the SSS showed a significant accuracy in detecting obstructive CAD (AUC 0.87, P < .001). Specifically, its accuracy was maintained also in patients with double (AUC 0.83; P < .001) or triple-vessels disease (AUC 0.79, P < .001), where CZT was able to correctly identify CAD extent in 64% of patients. On a per-vessel basis, CZT confirmed its high accuracy in detecting obstructive CAD (AUC 0.88, P < .001), independently from the involved coronary vessel. CONCLUSIONS: MPI performed on a CZT camera is highly accurate in detecting obstructive CAD, independently from the coronary artery involved and the overall disease burden. PMID- 26846368 TI - Use of coronary artery calcium scanning as a triage for cardiac ischemia testing. PMID- 26846370 TI - Flourishing in Health Care. AB - The purpose of this paper is to offer an account of 'flourishing' that is relevant to health care provision, both in terms of the flourishing of the individual patient and carer, and in terms of the flourishing of the caring institution. It is argued that, unlike related concepts such as 'happiness', 'well-being' or 'quality of life', 'flourishing' uniquely has the power to capture the importance of the vulnerability of human being. Drawing on the likes of Heidegger and Nussbaum, it is argued that humans are at once beings who are autonomous and thereby capable of making sense of their lives, but also subject to the contingencies of their bodies and environments. To flourish requires that one engages, imaginatively and creatively, with those contingencies. The experience of illness, highlighting the vulnerability of the human being, thereby becomes an important experience, stimulating reflection in order to make sense of one's life as a narrative. To flourish, it is argued, is to tell a story of one's life, realistically engaging with vulnerability and suffering, and thus creating a framework through which one can meaningful and constructively go on with one's life. PMID- 26846369 TI - Characterization of attenuation and respiratory motion artifacts and their influence on SPECT MP image evaluation using a dynamic phantom assembly with variable cardiac defects. AB - BACKGROUND: A phantom assembly that simulates the respiratory motion of the heart was used to investigate artifacts and their impact on defect detection. METHODS: SPECT/CT images were acquired for phantoms with and without small and large cardiac defects during normal and deep breathing, and also at four static respiratory phases. Acquisitions were reconstructed with and without AC, and with misalignment of transmission and emission scans. A quantitative analysis was performed to assess artifacts. Two physicians reported on defect presence or absence and their results were evaluated. RESULTS: All large defects were correctly reported. Attenuation reduced uptake in the basal LV walls, increasing FN physicians' reports for small defects. Respiratory motion reduced uptake mainly in the anterior and inferior walls increasing FP and FN reports on images without and with small defects, respectively. Artifacts due to misalignment between CT and SPECT scans in normal breathing phantoms did not influence the physicians' reports. CONCLUSIONS: Attenuation and respiratory motion correction should be applied to reduce artifacts before reporting on small defects in deep breathing conditions. Artifacts due to misalignment between CT and SPECT scans do not affect defect detection in normal breathing when the LV is co-registered in SPECT and CT images prior to AC. PMID- 26846371 TI - Delaunay algorithm and principal component analysis for 3D visualization of mitochondrial DNA nucleoids by Biplane FPALM/dSTORM. AB - Data segmentation and object rendering is required for localization super resolution microscopy, fluorescent photoactivation localization microscopy (FPALM), and direct stochastic optical reconstruction microscopy (dSTORM). We developed and validated methods for segmenting objects based on Delaunay triangulation in 3D space, followed by facet culling. We applied them to visualize mitochondrial nucleoids, which confine DNA in complexes with mitochondrial (mt) transcription factor A (TFAM) and gene expression machinery proteins, such as mt single-stranded-DNA-binding protein (mtSSB). Eos2-conjugated TFAM visualized nucleoids in HepG2 cells, which was compared with dSTORM 3D immunocytochemistry of TFAM, mtSSB, or DNA. The localized fluorophores of FPALM/dSTORM data were segmented using Delaunay triangulation into polyhedron models and by principal component analysis (PCA) into general PCA ellipsoids. The PCA ellipsoids were normalized to the smoothed volume of polyhedrons or by the net unsmoothed Delaunay volume and remodeled into rotational ellipsoids to obtain models, termed DVRE. The most frequent size of ellipsoid nucleoid model imaged via TFAM was 35 * 45 * 95 nm; or 35 * 45 * 75 nm for mtDNA cores; and 25 * 45 * 100 nm for nucleoids imaged via mtSSB. Nucleoids encompassed different point density and wide size ranges, speculatively due to different activity stemming from different TFAM/mtDNA stoichiometry/density. Considering twofold lower axial vs. lateral resolution, only bulky DVRE models with an aspect ratio >3 and tilted toward the xy-plane were considered as two proximal nucleoids, suspicious occurring after division following mtDNA replication. The existence of proximal nucleoids in mtDNA-dSTORM 3D images of mtDNA "doubling"-supported possible direct observations of mt nucleoid division after mtDNA replication. PMID- 26846372 TI - Ubenimex inhibits cell proliferation, migration and invasion by inhibiting the expression of APN and inducing autophagic cell death in prostate cancer cells. AB - Prostate cancer is the second most frequently diagnosed cancer in males worldwide and is commonly associated with metastasis. Moreover, in prostate cancer, aminopeptidase N (APN) expression is closely correlated with metastasis. Ubenimex, an APN inhibitor, is widely used as an adjunct therapy for cancer, enhancing the function of immunocompetent cells and conferring antitumor effects. However, due to the low expression of APN, it is rarely used to treat prostate cancer. Recently, the induction of autophagy as a molecular mechanism has been strongly connected with tumor cell death. Thus, we investigated whether ubenimex could inhibit cell proliferation, migration and invasion by downregulating APN expression to induce autophagic cell death in prostate cancer cells. The LNCaP and PC-3 cell lines were treated with different doses of ubenimex. Cell viability was measured using growth curve analysis and WST-8 proliferation assay. Autophagic cell death was assessed using fluorescence microscopy and acridine orange/ethidium bromide (AO/EB) staining. Protein expression was assessed by immunofluorescence and western blot analyses. Autophagosomes were evaluated using transmission electron microscopy. Wound-healing migration assays were performed to determine the migratory ability of the PC-3 cells. In addition, nude mice were used in the present study to examine PC-3 cell proliferation in vivo. The results revealed that APN expression differed between the metastatic and non-metastatic prostate cancer cells. In addition, ubenimex inhibited APN expression in the prostate cancer cells. Ubenimex increased prostate cancer cell death, as determined using the lactate dehydrogenase (LDH) cytotoxicity assay. This effect was accompanied by increased levels of LC3B. Furthermore, ubenimex inhibited PC-3 cell proliferation in vivo and in vitro. Ubenimex inhibited the cell migration and invasion in prostate cancer cells by downregulating APN expression. Finally, ubenimex induced autophagic cell death in both metastatic and non-metastatic prostate cancer cells. Based on these results, ubenimex appears to be an excellent adjunctive therapy for the treatment of prostate cancer. PMID- 26846373 TI - A Multi-Component Pheromone in the Urine of Dominant Male Tilapia (Oreochromis mossambicus) Reduces Aggression in Rivals. AB - Males often use scent to communicate their dominance, and to mediate aggressive and breeding behaviors. In teleost fish, however, the chemical composition of male pheromones is poorly understood. Male Mozambique tilapia, Oreochromis mossambicus, use urine that signals social status and primes females to spawn. The urinary sex pheromone directed at females consists of 5beta-pregnane 3alpha,17alpha,20beta-triol 3-glucuronate and its 20alpha-epimer. The concentration of these is positively correlated with male social rank. This study tested whether dominant male urine reduces aggression in receiver males, and whether the pregnanetriol 3-glucuronates also reduce male-male aggression. Males were allowed to fight their mirror image when exposed to either: i) water control or a chemical stimulus; ii) dominant male urine (DMU); iii) C18-solid phase (C18 SPE) DMU eluate; iv) C18-SPE DMU eluate plus filtrate; v) the two pregnanetriol 3 glucuronates (P3Gs); or vi) P3Gs plus DMU filtrate. Control males mounted an increasingly aggressive fight against their image over time. However, DMU significantly reduced this aggressive response. The two urinary P3Gs did not replicate the effect of whole DMU. Neither did the C18-SPE DMU eluate, containing the P3Gs, alone, nor the C18-SPE DMU filtrate to which the two P3Gs were added. Only exposure to reconstituted DMU (C18-SPE eluate plus filtrate) restored the aggression-reducing effect of whole DMU. Olfactory activity was present in the eluate and the polar filtrate in electro-olfactogram studies. We conclude that P3Gs alone have no reducing effect on aggression and that the urinary signal driving off male competition is likely to be a multi-component pheromone, with components present in both the polar and non-polar urine fractions. PMID- 26846374 TI - Endothelin-1 modulates methacholine-induced cutaneous vasodilatation but not sweating in young human skin. AB - KEY POINTS: Endothelin-1 (ET-1) is a potent endothelial-derived vasoconstrictor that may modulate cholinergic cutaneous vascular regulation. Endothelin receptors are also expressed on the human eccrine sweat gland, although it remains unclear whether ET-1 modulates cholinergic sweating. We investigated whether ET-1 attenuates cholinergic cutaneous vasodilatation and sweating through a nitric oxide synthase (NOS)-dependent mechanism. Our findings show that ET-1 attenuates methacholine-induced cutaneous vasodilatation through a NOS-independent mechanism. We also demonstrate that ET-1 attenuates cutaneous vasodilatation in response to sodium nitroprusside, suggesting that ET-1 diminishes the dilatation capacity of vascular smooth muscle cells. We show that ET-1 does not modulate methacholine-induced sweating at any of the administered concentrations. Our findings advance our knowledge pertaining to the peripheral control underpinning the regulation of cutaneous blood flow and sweating and infer that ET-1 may attenuate the heat loss responses of cutaneous blood flow, but not sweating. ABSTRACT: The present study investigated the effect of endothelin-1 (ET-1) on cholinergic mechanisms of end-organs (i.e. skin blood vessels and sweat glands) for heat dissipation. We evaluated the hypothesis that ET-1 attenuates cholinergic cutaneous vasodilatation and sweating through a nitric oxide synthase (NOS)-dependent mechanism. Cutaneous vascular conductance (CVC) and sweat rate were assessed in three protocols: in Protocol 1 (n = 8), microdialysis sites were perfused with lactated Ringer solution (Control), 40 pm, 4 nm or 400 nm ET-1; in Protocol 2 (n = 11) sites were perfused with lactated Ringer solution (Control), 400 nm ET-1, 10 mm N(G) -nitro-l-arginine (l-NNA; a NOS inhibitor) or a combination of 400 nm ET-1 and 10 mm l-NNA; in Protocol 3 (n = 8), only two sites (Control and 400 nm ET-1) were utilized to assess the influence of ET-1 on the dilatation capacity of vascular smooth muscle cells (sodium nitroprusside; SNP). Methacholine (MCh) was co-administered in a dose-dependent manner (0.0125, 0.25, 5, 100, 2000 mm, each for 25 min) at all skin sites. ET-1 at 400 nm (P < 0.05) compared to lower doses (40 pm and 4 nm) (all P > 0.05) significantly attenuated increases in CVC in response to 0.25 and 5 mm MCh. A high dose of ET-1 (400 nm) co-infused with l-NNA further attenuated CVC during 0.25, 5 and 100 mm MCh administration relative to the ET-1 site (all P < 0.05). Cutaneous vasodilatation in response to SNP was significantly blunted after administration of 400 nm ET-1 (P < 0.05). We show that ET-1 attenuates cutaneous vasodilatation through a NOS independent mechanism, possibly through a vascular smooth muscle cell-dependent mechanism, and methacholine-induced sweating is not altered by ET-1. PMID- 26846375 TI - Palladium-Catalyzed C-H Arylation of alpha,beta-Unsaturated Imines: Catalyst Controlled Synthesis of Enamine and Allylic Amine Derivatives. AB - A unique chemo- and regioselective alpha- and gamma-arylation of palladium azapentadienyl intermediates is presented. Two distinct catalysts and sets of conditions successfully controlled the regioselectivity of the arylation. These methods provide the first umpolung C-H functionalization of azapentadienyl palladium intermediates and enable the divergent synthesis of allylic amine and enamine derivatives, which are of significant interest in the pharmaceutical industry. PMID- 26846376 TI - Development of three-dimensional lung multicellular spheroids in air- and liquid interface culture for the evaluation of anticancer therapeutics. AB - Three-dimensional (3D) lung multicellular spheroids (MCS) in liquid-covered culture (LCC) and air-interface culture (AIC) conditions have both been developed for the evaluation of aerosol anticancer therapeutics in solution and aerosols, respectively. The MCS were formed by seeding lung cancer cells on top of collagen where they formed spheroids due to the prevalence of cell-to-cell interactions. LCC MCS were exposed to paclitaxel (PTX) in media whereas AIC MCS were exposed to dry powder PEGylated phospholipid aerosol microparticles containing paclitaxel. The difference in viability for 2D versus 3D culture for both LCC and AIC was evaluated along with the effects of the particles on lung epithelium via transepithelial electrical resistance (TEER) measurements. For LCC and AIC conditions, the 3D spheroids were more resistant to treatment with higher IC50 values for A549 and H358 cell lines. TEER results initially indicated a decrease in resistance upon drug or particle exposure, however, these values increased over the course of several days indicating the ability of the cells to recover. Overall, these studies offer a comprehensive in vitro evaluation of aerosol particles used in the treatment of lung cancer while introducing a new method for culturing lung cancer MCS in both LCC and AIC conditions. PMID- 26846377 TI - Impaired barrier function in patients with house dust mite-induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression. AB - BACKGROUND: Tight junction (TJ) defects have recently been associated with asthma and chronic rhinosinusitis. The expression, function, and regulation of nasal epithelial TJs remain unknown in patients with allergic rhinitis (AR). OBJECTIVE: We investigated the expression, function, and regulation of TJs in the nasal epithelium of patients with house dust mite (HDM)-induced AR and in an HDM induced murine model of allergic airway disease. METHODS: Air-liquid interface cultures of primary nasal epithelial cells of control subjects and patients with HDM-induced AR were used for measuring transepithelial resistance and passage to fluorescein isothiocyanate-dextran 4 kDa (FD4). Ex vivo transtissue resistance and FD4 permeability of nasal mucosal explants were measured. TJ expression was evaluated by using real-time quantitative PCR and immunofluorescence. In addition, the effects of IL-4, IFN-gamma, and fluticasone propionate (FP) on nasal epithelial cells were investigated in vitro. An HDM murine model was used to study the effects of allergic inflammation and FP treatment on transmucosal passage of FD4 in vivo. RESULTS: A decreased resistance in vitro and ex vivo was found in patients with HDM-induced AR, with increased FD4 permeability and reduced occludin and zonula occludens-1 expression. AR symptoms correlated inversely with resistance in patients with HDM-induced AR. In vitro IL-4 decreased transepithelial resistance and increased FD4 permeability, whereas IFN gamma had no effect. FP prevented IL-4-induced barrier dysfunction in vitro. In an HDM murine model FP prevented the allergen-induced increased mucosal permeability. CONCLUSION: We found impaired nasal epithelial barrier function in patients with HDM-induced AR, with lower occludin and zonula occludens-1 expression. IL-4 disrupted epithelial integrity in vitro, and FP restored barrier function. Better understanding of nasal barrier regulation might lead to a better understanding and treatment of AR. PMID- 26846378 TI - A further wheat allergen for baker's asthma: Tri a 40. PMID- 26846380 TI - In response to the letter to the editor from Sylvia van Dyk et al. regarding our editorial "High-tech image-guided therapy vs. low-tech, simple, cheap gynecologic brachytherapy". PMID- 26846379 TI - Reorganization of Intact Descending Motor Circuits to Replace Lost Connections After Injury. AB - Neurons have a limited capacity to regenerate in the adult central nervous system (CNS). The inability of damaged axons to re-establish original circuits results in permanent functional impairment after spinal cord injury (SCI). Despite abortive regeneration of axotomized CNS neurons, limited spontaneous recovery of motor function emerges after partial SCI in humans and experimental rodent models of SCI. It is hypothesized that this spontaneous functional recovery is the result of the reorganization of descending motor pathways spared by the injury, suggesting that plasticity of intact circuits is a potent alternative conduit to enhance functional recovery after SCI. In support of this hypothesis, several studies have shown that after unilateral corticospinal tract (CST) lesion (unilateral pyramidotomy), the intact CST functionally sprouts into the denervated side of the spinal cord. Furthermore, pharmacologic and genetic methods that enhance the intrinsic growth capacity of adult neurons or block extracellular growth inhibitors are effective at significantly enhancing intact CST reorganization and recovery of motor function. Owing to its importance in controlling fine motor behavior in primates, the CST is the most widely studied descending motor pathway; however, additional studies in rodents have shown that plasticity within other spared descending motor pathways, including the rubrospinal tract, raphespinal tract, and reticulospinal tract, can also result in restoration of function after incomplete SCI. Identifying the molecular mechanisms that drive plasticity within intact circuits is crucial in developing novel, potent, and specific therapeutics to restore function after SCI. In this review we discuss the evidence supporting a focus on exploring the capacity of intact motor circuits to functionally repair the damaged CNS after SCI. PMID- 26846381 TI - Brachytherapy vs. external beam radiotherapy for choroidal melanoma: Survival and patterns-of-care analyses. AB - PURPOSE: No modern randomized trials exist comparing external beam radiotherapy (EBRT) and plaque brachytherapy (BT) for choroidal melanoma, and the optimal treatment modality is currently unknown. This study compares the patterns of care and efficacy of EBRT vs. BT based on data in the Surveillance, Epidemiology, and End Results database. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database was queried for patients aged 20-79 diagnosed with choroidal melanoma from 2004 to 2011, treated with EBRT or BT; included patients were clinically T1-T4, N0, and M0. Overall survival and cause-specific survival curves were calculated by the Kaplan-Meier method. Univariate and multivariate analyses were performed in the survival and patterns-of-care analyses. RESULTS: A total of 1004 cases (380 EBRT and 624 BT) were included in the survival analysis. There was no difference in the 5-year overall survival (83.3% EBRT vs. 82.5% BT, p = 0.69) and 5-year cause-specific survival (88.3% EBRT vs. 88.3% BT, p = 0.92). In the survival analysis, older age and advanced tumor stage were predictors of increased risk of death. In the patterns-of-care analysis, later year of diagnosis and smaller tumor stage were predictors of BT use. CONCLUSIONS: Advanced tumor stage and older age seem to be independent predictors for risk of death from choroidal melanoma. The use of BT favors smaller tumors and later year of diagnosis. There is no difference in survival between those treated with EBRT or BT, and the utilization of BT is increasing. PMID- 26846383 TI - Bang for the Buck: How the ACR Adds Value to Our Practices. PMID- 26846384 TI - I Can't Keep Up. PMID- 26846382 TI - Expression and function of microRNA-27b in hepatocellular carcinoma. AB - It has been reported that microRNAs (miRs) have key roles in tumorigenesis via inhibition of their target genes. Dysregulation of miR-27b has been detected in numerous types of human cancer, including hepatocellular carcinoma (HCC); however, the detailed role of miR-27b in HCC has yet to be elucidated. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to examine the mRNA and protein expression levels. Transwell assay and wound healing assay were used to determine cell invasion and migration. Luciferase reporter assay was to confirm the targeting relationship. The present study demonstrated that the expression levels of miR-27b were significantly increased in HCC cell lines, as compared with in normal human liver cells. In addition, miR-27b was frequently upregulated in HCC tissues, as compared with in normal adjacent tissues; the expression levels of miR-27b were increased in 77.1% (27/35) of the HCC tissue samples. Furthermore, elevated miR-27b expression levels were significantly correlated with tumor differentiation, Tumor Node Metastasis stage and vascular invasion (P<0.05). Knockdown of miR-27b expression inhibited HCC cell migration and invasion. Furthermore, Sprouty 2 (Spry2) was identified as a novel target of miR-27b in HCC HepG2 cells, and the protein expression levels of Spry2 were negatively regulated by miR-27b in HepG2 cells. Overexpression of Spry2 suppressed HCC cell migration and invasion, whereas downregulation of Spry2 reversed the suppressive effects of miR-27b inhibition on HCC cell migration and invasion. The results of the present study suggested that miR-27b may promote the migration and invasion of HCC cells, at least partially by suppressing Spry2 expression. Therefore, the miR-27b/Spry2 axis may be considered a potential therapeutic target for HCC. PMID- 26846385 TI - The 2016 Bruce J. Hillman, MD, Fellows in Scholarly Publication. PMID- 26846386 TI - Author's Reply. PMID- 26846387 TI - When Reporting Adverse Events, Less = More. PMID- 26846388 TI - Leveraging Imperfect Data Sets to Draw New Conclusions: Radiogenomics' True Value? PMID- 26846389 TI - Author's Reply. PMID- 26846391 TI - Assessment of Clinician Response to Radiology Alerts. PMID- 26846390 TI - ACR Appropriateness Criteria Osteonecrosis of the Hip. AB - Osteonecrosis of the hip (Legg-Calve-Perthes) is a common disease, with 10,000 20,000 symptomatic cases annually in the United States. The disorder affects both adults and children and is most frequently associated with trauma and corticosteroid usage. The initial imaging evaluation of suspected hip osteonecrosis is done using radiography. MRI is the most sensitive and specific imaging modality for diagnosis of osteonecrosis of the hip. The clinical significance of hip osteonecrosis is dependent on its potential for articular collapse. The likelihood of articular collapse is significantly increased with involvement of greater than 30%-50% of the femoral head area, which is optimally evaluated by MRI, often in the sagittal plane. Contrast-enhanced MRI may be needed to detect early osteonecrosis of the hip in pediatric patients, revealing hypoperfusion. In patients with a contraindication for MRI, use of either CT or bone scintigraphy with SPECT (single-photon emission CT) are alternative radiologic methods of assessment. Imaging helps guide treatment, which may include core decompression, osteotomy, and ultimately, need for joint replacement. The ACR Appropriateness Criteria((r)) are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. PMID- 26846392 TI - Quality Improvement and Leadership Development. PMID- 26846393 TI - Peer Review in Radiology: A Resident and Fellow Perspective. AB - PURPOSE: The purpose of this study was to explore Canadian radiology residents' and fellows' understanding, attitudes, opinions, and preferences toward peer review. METHODS: An Internet-based anonymous questionnaire designed to understand one's familiarity, attitudes, opinions, and preferences toward peer review was distributed to radiology residents and fellows across Canada. Data were analyzed using descriptive statistics, and answers were stratified by level of training. RESULTS: A total of 136 trainees responded to the survey with 92 completed survey responses available for descriptive statistics. Approximately half of respondents are familiar with peer review (49%), and 39% of trainees are involved in peer review. Most respondents (92%) expressed an interest in learning more about peer review; believe that it should be incorporated into the residency training curriculum (86%), be mandatory (72%), and that current participation will increase odds of future participation (91%). Most trainees (80%) are comfortable advising one another about errors, but less comfortable advising staff (21%). CONCLUSIONS: Residents and fellows welcome the opportunity to learn more about peer review and believe it should be incorporated into the residency training curriculum. Understanding the attitudes and perceptions held by trainees regarding peer review is important, as a means to optimize education and maximize current and future participation in peer review. PMID- 26846394 TI - What Radiology Can Learn From the Management Consulting Industry. PMID- 26846395 TI - An Organizational Perspective and a Team Approach: Keys to Successful Business Planning. PMID- 26846396 TI - The Development and Role of Imaging Informatics. PMID- 26846397 TI - Comment on "Treatment persistence after initiating basal insulin in type 2 diabetes patients: A primary care database analysis": By Pscherer S et al. published in Prim. Care Diabetes 2015 Oct;9(5):377-84. PMID- 26846398 TI - Collecting Biological Measures for Research With Children and Adolescents. PMID- 26846399 TI - Echinacoside suppresses pancreatic adenocarcinoma cell growth by inducing apoptosis via the mitogen-activated protein kinase pathway. AB - The clinical application of natural products derived from traditional Chinese medicine has gained attention in cancer chemotherapeutics. Echinacoside (ECH), one of the phenylethanoids, isolated from the stems of Cistanches salsa (a Chinese herbal medicine) has tissue-protective and anti-apoptotic effects on the central nervous system. However, it remains largely elusive whether ECH possesses tumor suppressive activity. In the present study, it was demonstrated that ECH can markedly inhibit the proliferation of pancreatic adenocarcinoma cells by inducing the production of reactive oxygen species and the perturbation of mitochondrial membrane potential and thus triggering apoptosis. Furthermore, it was elucidated that ECH represses tumor cell growth through modulating MAPK activity. In conclusion, this study reveals an novel function of ECH in preventing cancer development, and implies that the usage of ECH could be a potential chemotherapeutic strategy for cancer. PMID- 26846400 TI - Spinocerebellar ataxia type 2: Measures of saccade changes improve power for clinical trials. AB - BACKGROUND: Saccadic eye movement abnormalities are common in patients with spinocerebellar ataxia type 2, but it is unclear how these alterations progress over time. The aim of this study was to assess the progression of saccade involvement in spinocerebellar ataxia type 2 patients, identify its main determinants, and evaluate its usefulness as outcome measures in clinical trials. METHODS: A prospective 5-year follow-up study was performed with 30 spinocerebellar ataxia type 2 patients and their matched healthy controls, who were evaluated a total of four times by clinical and electrooculographical assessments of horizontal saccades and by the scoring of ataxia. RESULTS: Patients showed significant decreases in saccade peak velocity and saccade accuracy as well as increases of saccadic latency during the follow-up period. Annual progression rates were significantly higher in patients compared to controls. Faster progression rates of saccade slowing were associated with higher trinucleotide cytosine-adenine-guanine repeat expansions. Sample-size estimates for two-arm trials would require 19 patients per group to detect a 50% reduction in disease progression using saccade peak velocity as outcome variable, but 44 and 124 patients using saccade latency and accuracy, respectively (power, 80%; alpha = 0.05). CONCLUSIONS: Electrooculographical measures of saccade changes are useful for the objective quantification of disease course in spinocerebellar ataxia type 2. The progression rate of saccade slowing is influenced by the expansion size, providing novel insight into the cumulative polyglutamine neurotoxicity, and supporting the usefulness of saccade peak velocity as a sensitive biomarker during the natural history of the disease, and as suitable outcome measure for therapeutic trials. PMID- 26846402 TI - Evaluation of a Veress needle for the fluid egress system of stifle arthroscopy in toy dog breeds. AB - OBJECTIVES: The aim of this study was to evaluate the use of a Veress needle as a fluid egress system for stifle arthroscopy in toy dog breeds. METHODS: Cadaveric canine stifle joints (n = 32) were prepared to induce an artificial intra articular haemorrhagic effect, followed by stifle arthroscopy. The stifles were randomly assigned to one of three groups, and a fluid egress portal was established using a Veress needle (VN), a standard egress cannula (SE), or an intravenous catheter stylet (CS). Time to establish the egress portal, arthroscopic visibility, and egress portal performance were evaluated during the arthroscopy. After the arthroscopic examinations, iatrogenic cartilage lesions were identified and analysed using the percentage area of cartilage damage (%ACD). RESULTS: The overall arthroscopic visibility and egress portal performance were not significantly different among the groups. The egress portal establishment was faster for the VN (33 sec) and the CS (34 sec) groups than for the SE (43 sec) group (p = 0.001). On gross joint examination, no iatrogenic laceration was found in the VN group, whereas four out of 10 of the SE and two out of 10 of the CS specimens had linear cartilage excoriation on the stifle joints. The %ACD score of the VN group was lower than those of the SE group (p = 0.009) and the CS group (p = 0.001). CLINICAL SIGNIFICANCE: The Veress needle method used in this study was useful to establish a fluid egress system and limit iatrogenic cartilage excoriations. This technique could become the method of choice for stifle arthroscopy, especially in smaller dogs. PMID- 26846401 TI - Structures and Electronic Properties of Different CH3NH3PbI3/TiO2 Interface: A First-Principles Study. AB - Methylammonium lead iodide perovskite, CH3NH3PbI3, has attracted particular attention due to its fast increase in efficiency in dye sensitization TiO2 solid state solar cells. We performed first-principles calculations to investigate several different types of CH3NH3PbI3/TiO2 interfaces. The interfacial structures between the different terminated CH3NH3PbI3 and phase TiO2 are thoroughly explored, and the calculated results suggest that the interfacial Pb atoms play important roles in the structure stability and electronic properties. A charge transfer from Pb atoms to the O atoms of TiO2 lead to the band edge alignment of Pb-p above Ti-d about 0.4 eV, suggesting a better carries separation. On the other hand, for TiO2, rutile (001) is the better candidate due to the better lattice and atoms arrangement match with CH3NH3PbI3. PMID- 26846403 TI - Reconstruction of nasal tip support in primary, open approach septorhinoplasty : A retrospective analysis between the tongue-in-groove technique and the columellar strut. AB - The reconstruction of the nasal tip support is one of the most essential issues in septorhinoplasty. A comparison of the results after using the tongue-in-groove technique and the columellar strut technique was the target of this study. Thirty three patients who underwent a primary, open approach septorhinoplasty using the above-mentioned techniques were retrospectively analyzed. The gain in tip rotation postoperatively, the sensitivity and the rigidity of the nasal tip and the aesthetic outcome after surgery were examined and evaluated. Both techniques led to an increase in nasal tip rotation postoperatively. The gain in rotation was higher in patients, treated with the tongue-in-groove technique (p = 0.0052). The sensitivity of the tip region in the tongue-in-groove group of patients was significantly lower than that in the columellar strut group of patients (p = 0.0424). Both techniques led to high percentages of tip rigidity after surgery with satisfactory aesthetic results though. The tongue-in-groove technique and the columellar strut technique are both reliable techniques for reconstructing the nasal tip support and correcting a droopy tip. Although the tongue-in-groove technique might result in a more significant increase in tip rotation, it leads to less sensitivity in the tip region. PMID- 26846404 TI - Association of Biofilm Formation, Psl Exopolysaccharide Expression, and Clinical Outcomes in Pseudomonas aeruginosa Keratitis: Analysis of Isolates in the Steroids for Corneal Ulcers Trial. AB - IMPORTANCE: Bacterial virulence factors are increasingly recognized as important in the understanding of clinical infections. OBJECTIVE: To determine whether 2 potential virulence factors, in vitro biofilm formation and Psl exopolysaccharide (EPS) expression, influence clinical presentation or outcomes in Pseudomonas aeruginosa keratitis. DESIGN, SETTING, AND PARTICIPANTS: Laboratory investigation using P aeruginosa clinical isolates from the double-blind Steroids for Corneal Ulcers Trial (SCUT), which included patients at Aravind Eye Hospital, Proctor Foundation, University of California, San Francisco, and Dartmouth-Hitchcock Medical Center. SCUT was conducted from September 1, 2006, through February 22, 2010. All data used in this study were obtained during this period. Pseudomonas aeruginosa clinical isolates from SCUT were evaluated for in vitro biofilm formation, and Psl EPS expression was assessed using an anti-Psl monoclonal antibody (mAb) enzyme-linked immunosorbent assay. Planktonic growth kinetics and the susceptibility to anti-Psl mAb-mediated opsonophagocytic killing (OPK) were also evaluated in a subset of isolates. Linear regression assessed associations between SCUT patients' visual acuity and their corresponding biofilm formation and Psl EPS expression. Generalized estimating equation regression models were used to assess whether the change in visual acuity among SCUT patients was associated with Psl EPS expression or biofilm formation. MAIN OUTCOMES AND MEASURES: Biofilm formation, Psl production, OPK, and visual acuity. RESULTS: The P aeruginosa SCUT strains produced a mean (SD) in vitro biofilm score of 1.06 (0.32) (range 0.17-2.12). A 1-unit increase in biofilm was associated with a worse visual acuity of 2 lines measured in SCUT patients at baseline (0.20 logMAR; 95% CI, -0.03 to 0.44; P = .09) and 3 months (0.21 logMAR; 95% CI, 0.003 to 0.44; P = .047). Of 101 confirmed P aeruginosa SCUT isolates, 100 expressed Psl EPSs. In addition, all Psl-positive strains evaluated in the OPK assay were susceptible to anti-Psl mAb-mediated OPK. CONCLUSIONS AND RELEVANCE: The ability of P aeruginosa keratitis isolates to form biofilms in vitro was correlated with worse vision at presentation and after 3 months in SCUT. Ninety-nine percent of P aeruginosa keratitis isolates from SCUT produced Psl EPSs, and 100% of these evaluated Psl-positive isolates were susceptible to anti-Psl mAb-mediated OPK. These data indicate that biofilm formation and Psl EPSs may be candidate targets for novel therapeutics against P aeruginosa keratitis. PMID- 26846405 TI - Personal Descriptions of Life Before and After Bariatric Surgery From Overweight or Obese Men. AB - Bariatric surgery is now a common weight loss solution for morbidly obese men where meaningful weight reduction and improvements in quality of life have been identified postsurgery. As the majority of surgical candidates are female, there exists a paucity of literature relating to the experience of males undergoing bariatric surgery. In this study, a qualitative descriptive-exploratory design was used to explore body image descriptions, adaptation of a new lifestyle, new boundaries postsurgery, and any barriers seeking consultation for surgery. Six males who had undergone bariatric surgery were recruited in Australia. Data were collected and analyzed using NVivo between May and October 2014. The themes emerging from the data included living in an obese body, life before surgery, decision making for surgery, and life after surgery. The participants collectively reported that life before surgery was challenging. They described the changes the surgery had made in their lives including positive changes to their health, body image, social lives, and self-esteem. Some participants preferred not to tell others their intentions for surgery due to perceived stigma. The men in this study also described a lack of information available to them depicting male perspectives, a possible barrier for men seeking weight loss surgery options. Implications for practice highlighted in these results relate to a greater need for accessible information specific to men based on real-life experiences. PMID- 26846407 TI - No Man Left Behind: Effectively Engaging Male Military Veterans in Counseling. AB - Ex-military men have emerged as a vulnerable subgroup for mental illness amid long-standing trends signaling men's reticence to seek professional help. Less explored is how men engage or disengage when they actually do enter helping programs. Contrasting decades of quantitative research pairing masculine ideology with low help seeking (i.e., describing the problem), this article draws on qualitative data to distill factors that help men become engaged and committed to counseling (i.e., identifying solutions). Shared is an evaluation of a treatment program with high success rates and virtually no dropouts-a unique occurrence in men's counseling. Enhanced Critical Incident Technique data suggest that helping men feel competent and free from judgment in the company of down-to-earth peers and genuine practitioners are instrumental in helping men draw benefit from counseling. While appealing to male gender roles may be critical in recruiting men to counseling, men can transition to embrace virtues (i.e., that might be shared by men and women alike) and universal human needs as counseling progresses. PMID- 26846406 TI - The Association of Erectile Dysfunction and Cardiovascular Disease: A Systematic Critical Review. AB - Despite strong association between erectile dysfunction (ED) and cardiovascular disease (CVD), there is a paucity of clear clinical guidelines detailing when and how to evaluate for ED in patients with known CVD, or vice versa. This systematic review discuss the role of cardiologists and urologists in the characterization of risk and management of CVD in the setting of ED, as well as contrasting the current evaluation of CVD and ED from the standpoint of published consensus statements. A comprehensive literature review utilizing MEDLINE(r), the Cochrane Library(r) Central Search, and the Web of Science was performed to identify all published peer-reviewed articles in the English language describing ED and CVD across various disciplines. There is strong consensus that men with ED should be considered at high risk of CVD. Available risk assessment tools should be used to stratify the coronary risk score in each patient. The 2012 Princeton III Consensus Conference expanded on existing cardiovascular recommendations, proposing an approach to the evaluation and management of cardiovascular risk in men with ED and no known CVD. This systematic review highlights the similarities and differences of the existing clinical guidelines and recommendations regarding assessment and management of ED and CVD, as well as the pathophysiological linkage between ED and CVD, which may permit physicians, including urologists, to perform opportunistic screening and initiate secondary prophylaxis with regard to cardiovascular risk factors, particularly in young, nondiabetic men with ED. PMID- 26846410 TI - Synthesis and characterization of chiral aza-macrocycles and study of their enantiomer recognition ability for organo-phosphoric acid and phosphonic acid derivatives by 31P NMR and fluorescence spectroscopy. AB - Two diastereomers of optically active N,O-containing new macrocycles with dual chirality of the ring and pendent group were synthesized and characterized. The difference in the accessibility of the cavity was explored to discriminate the enantiomers of the derivatives of organo-phosphoric and phosphonic acids by (31)P NMR and fluorescence spectroscopy. PMID- 26846409 TI - Effect of silencing HOXA5 gene expression using RNA interference on cell cycle and apoptosis in Jurkat cells. AB - Acute lymphocytic leukemia (ALL) is a common malignant tumor with a high morbidity rate among children, accounting for approximately 80% of leukemia cases. Although there have been improvements in the treatment of patients frequent relapse lead to a poor prognosis. The aim of the present study was to determine whether HOXA5 may be used as a target for gene therapy in leukemia in order to provide a new treatment. Mononuclear cells were extracted from the bone marrow according to the clinical research aims. After testing for ALL in the acute stage, the relative mRNA and protein expression of HOXA5 was detected in the ALL remission groups (n=25 cases per group) and the control group [n=20 cases, immune thrombocytopenia (ITP)]. Gene silencing by RNA interference (RNAi) was used to investigate the effect of silencing HOXA5 after small interfering RNA (siRNA) transfection to Jurkat cells. The HOXA5-specific siRNA was transfected to Jurkat cells using lipofectamine. The experiment was divided into the experimental group (liposomal transfection of HOXA5 targeting siRNA), the negative control group (liposomal transfection of cells with negative control siRNA) and the control group (plus an equal amount of cells and culture media only). Western blotting and quantitative fluorescent polymerase chain reaction (QF-PCR) were used to detect the relative HOXA5 mRNA expression and protein distribution in each cell group. Cell distribution in the cell cycle and the rate of cells undergoing apoptosis were determined using flow cytometry. The expression of HOXA5 at the mRNA and protein levels in the acute phase of ALL was significantly higher than that in ALL in the remission and control groups. In cells transfected with HOXA5-specific siRNA, the expression of HOXA5 at the mRNA and protein levels decreased significantly (P<0.05). The distribution of cells in the cell cycle was also altered. Specifically, more cells were present in the G0/G1 phase compared to the S phase (P<0.05). In addition, the apoptotic rate was significantly higher in cells transfected with HOXA5-specific siRNA (P<0.05). In conclusion, high expression levels of HOXA5 mRNA and protein in children with ALL indicate that HOXA5 is closely associated with childhood ALL. In addition, HOXA5 specific siRNA effectively silences HOXA5 gene expression and induces apoptosis and cell-cycle arrest in Jurkat cells, thus inhibiting cell proliferation. PMID- 26846408 TI - Comprehensive Assessment of Health Needs of Young Minority Males Attending a Family Planning Clinic. AB - The objective of this study was to assess the overall health, including sexual and reproductive health (SRH) knowledge and needs, sexual behaviors, and testicular health practices among young minority males. Anonymous questionnaires were administered to 18- to 25-year-old males receiving services at health clinics in a large southwestern U.S. city. The survey was completed by 258 males with a mean age of 20.8 years. Most young males (67.1%) identified as African American, and 32.9% as Hispanic. Results suggest study participants lack SRH knowledge related to pregnancy and condom effectiveness, and engage in risky sexual behavior including not using birth control at their last sexual encounter. Although 21.6% of participants had a sexually transmitted infection (STI) in the past year, approximately 80% perceived their STI/HIV risk as very low or low. Respondents had low engagement and lack of knowledge of testicular health practices. The majority of respondents (71.1%) reported having been in a physical fight one or more times and 18.1% reported being victims of intimate partner violence. These data support a need for comprehensive health services for minority young males. PMID- 26846411 TI - [The great apophyses: Functional strain and relevance]. AB - BACKGROUND: The structure of apophyses and apophyseal growth plates is not substantially different from those of epiphyses and epiphyseal growth plates. In contrast to epiphyseal growth plates, apophyses and apophyseal growth plates do not contribute to the longitudinal growth of the extremity. They are associated with their adjacent joints, triggering the lengths of their lever arms and influencing their external shape and internal architecture. The formative stimulus on apophyses is given by muscles and tendons inserting at the apophysis or canopying the apophsis. APOPHYSIS OF THE GREATER TROCHANTER: The apophysis of the greater trochanter significantly contributes to the lever arm length of the hip joint. Its growth activity triggers the neck-shaft angle and finally the centration of the hip joint. TIBIAL APOPHYSIS: The tibial apophysis interacts with the slope of the proximal tibia and hereby influences the sagittal stability of the knee joint. A damage to the growth plate of the tibial tubercle leads to an anteverted tibial slope and a genu recurvatum difficult to treat. CALCANEAL APOPHYSIS: The calcaneal apophysis determines the length and position of the calcaneus and herewith influences the torque of the ankle joint. In a nutshell you may regard the apophyses as adjusting screws acting on their adjacent joints and influencing their growth, form and structure. PMID- 26846412 TI - Ancestry informative markers and selected single nucleotide polymorphisms in immunoregulatory genes on preterm labor and preterm premature rupture of membranes: a case control study. AB - BACKGROUND: A genetic predisposition to Preterm Labor (PTL) and Preterm Premature Rupture of Membranes (PPROM) has been suggested; however the relevance of polymorphisms and ancestry to susceptibility to PTL and PPROM in different populations remains unclear. The aim of this study was to evaluate the contribution of maternal and fetal SNPs in the IL1B, IL6, IL6R, TNFA, TNFR, IL10, TLR2, TLR4, MMP9, TIMP1 and TIMP2 genes and the influence of ancestry background in the susceptibility to PTL or PPROM in Brazilian women. METHODS: Case-control study conducted at a tertiary hospital in Sao Paulo State, Brazil. We included women with PTL or PPROM and their babies (PTL: 136 women and 88 babies; PPROM: 65 women and 44 babies). Control group included 402 mother-babies pairs of term deliveries. Oral swabs were collected for identification of AIMs by fragment analysis and SNPs by Taqman(r) SNP Genotyping Assays and PCR. Linkage Disequilibrium and Hardy-Weinberg proportions were evaluated using Genepop 3.4. Haplotypes were inferred using the PHASE algorithm. Allele, genotype and haplotype frequencies were compared by Fisher's exact test or chi (2) and Odds Ratio. Logistic regression was performed. Clinical and sociodemographic data were analyzed by Fisher's exact test and Mann-Whitney. RESULTS: PTL was associated with European ancestry and smoking while African ancestry was protective. The fetal alleles IL10-592C (rs800872) and IL10-819C (rs1800871) were also associated with PTL and the maternal haplotype TNFA-308G-238A was protective. Maternal presence of IL10-1082G (rs1800896) and TLR2A (rs4696480) alleles increased the risk for PPROM while TNFA-238A (rs361525) was protective. Family history of PTL/PPROM was higher in cases, and time to delivery was influenced by IL1B-31T (rs1143627) and TLR4-299G (rs4986790). CONCLUSION: There is an association between European ancestry and smoking and PTL in our Brazilian population sample. The presence of maternal or fetal alleles that modify the inflammatory response increase the susceptibility to PTL and PPROM. The family history of PTL/PPROM reinforces a role for genetic polymorphisms in susceptibility to these outcomes. PMID- 26846414 TI - Predicting sarcopenia from functional measures among community-dwelling older adults. AB - Sarcopenia is defined as age-related lean tissue mass (LTM) loss resulting in reduced muscular strength, physical function, and mobility. Up to 33 % of older adults currently are sarcopenic, with likely many more undiagnosed. The purpose of this investigation was to predict sarcopenia status from easily accessible functional measures of community-dwelling older adults. Forty-three community dwelling older adults (n = 32 females and n = 11 males) participated in the present investigation. Inclusion criteria included >=65 years of age, mini-mental state examination score >=24, and no falls within previous 12 months. All subjects completed their appendicular skeletal mass (ASM) assessment via dual energy X-ray absorptiometry (DXA) and were categorized as either sarcopenic or non-sarcopenic. Physical assessments included 10-m usual walk, hand-grip (HG) strength, 6-min walk, 8-ft up-and-go, 30-s chair stand, 30-s arm curl, and sit-to stand muscular power. A forward, stepwise multiple regression analysis revealed that age, sex, weight, height, 10-m walk, HG, and sit-to-stand muscular power account for 96.1 % of the variance in ASM. The area under the curve was 0.92 for correctly identifying sarcopenic participants compared to their actual classification. This is the first prediction model used to identify sarcopenia based on parameters of demographic and functional fitness measures in community dwelling older adults. The ability to accurately identify sarcopenia in older adults is imperative to their quality of life and ability to perform activities of daily living. PMID- 26846413 TI - Augmenting strength-to-weight ratio by body weight unloading affects walking performance equally in obese and nonobese older adults. PMID- 26846416 TI - Association of IL23R polymorphism (rs7530511) with intracerebral hemorrhage in Korean population. AB - Cytokines and their receptors are involved in the development of intracerebral hemorrhage (ICH). Interleukin 23 receptor (IL23R) has been implicated in numerous inflammatory and immune diseases. In this study, we investigated whether single nucleotide polymorphisms (SNPs) of IL23R were associated with the susceptibility of ICH in Korean population. Two coding region SNPs (cSNPs) [rs1884444 (Gln3His), and rs7530511 (Leu310Pro)] were selected, and genotyped in 167 ICH patients and 377 control subjects using direct sequencing. Of two cSNPs, only rs7530511 showed a significant association with ICH in codominant model (C/T vs. C/C, P = 0.017, odds ratio (OR) 4.15, 95 % confidential interval (CI) 1.27-13.58). Allele frequency analysis also revealed that rs7530511 was associated with ICH (P = 0.023, OR 3.68, 95 % CI 1.19-11.32). The frequency of the T allele was increased in the ICH patients, compared to the control subjects. These results suggest that IL23R may contribute to the development of ICH. PMID- 26846418 TI - Gait variability in multiple sclerosis: a better falls predictor than EDSS in patients with low disability. AB - This longitudinal study aims to compare the role of stride time variability (STV) and EDSS for predicting falls in 50 patients with multiple sclerosis with low disability. 21.7 % developed falls (follow-up: 22 months). STV (IRR: 1.73, 95 % CI: 1.23-2.41, p = 0.001) and EDSS (IRR: 2.29, 95 % CI: 1.35-3.90, p = 0.002) were associated with the number of falls. Adding STV to EDSS improves the predictive power of the model from 21 to 26 %, but not adding EDSS to STV. PMID- 26846419 TI - Preceding bronchial cutting for exposure of the pulmonary artery buried in scar tissue after chemoradiotherapy. AB - It is often difficult to expose the pulmonary artery buried in a scar tissue, especially in lung cancer patients that responded well to neoadjuvant chemoradiotherapy. Difficulty to access pulmonary artery branches may lead to potentially unnecessary pneumonectomy. To complete lobectomy in such cases, a technique with preceding bronchial cutting for exposure of the pulmonary artery is presented. After dissecting the pulmonary vein, the lobar bronchus is cut from the opposite side of the pulmonary artery with scissors. The back wall of the lobar bronchus is cut using a surgical knife from the luminal face, which can expose the pulmonary artery behind the bronchial stump and then complete lobectomy. Fourteen patients have been treated using the present technique, enabling complete resection by lobectomy (including sleeve lobectomy in 3 patients) without major bleeding. The present procedure can expose pulmonary artery buried in scar tissue, resulting in making the lobectomy safer. PMID- 26846415 TI - Obesity and related consequences to ageing. AB - Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases. PMID- 26846417 TI - A CURLY LEAF homologue controls both vegetative and reproductive development of tomato plants. AB - The Enhancer of Zeste Polycomb group proteins, which are encoded by a small gene family in Arabidopsis thaliana, participate to the control of plant development. In the tomato (Solanum lycopersicum), these proteins are encoded by three genes (SlEZ1, SlEZ2 and SlEZ3) that display specific expression profiles. Using a gene specific RNAi strategy, we demonstrate that repression of SlEZ2 correlates with a general reduction of H3K27me3 levels, indicating that SlEZ2 is part of an active PRC2 complex. Reduction of SlEZ2 gene expression impacts the vegetative development of tomato plants, consistent with SlEZ2 having retained at least some of the functions of the Arabidopsis CURLY LEAF (CLF) protein. Notwithstanding, we observed significant differences between transgenic SlEZ2 RNAi tomato plants and Arabidopsis clf mutants. First, we found that reduced SlEZ2 expression has dramatic effects on tomato fruit development and ripening, functions not described in Arabidopsis for the CLF protein. In addition, repression of SlEZ2 has no significant effect on the flowering time or the control of flower organ identity, in contrast to the Arabidopsis clf mutation. Taken together, our results are consistent with a diversification of the function of CLF orthologues in plants, and indicate that although partly conserved amongst plants, the function of EZ proteins need to be newly investigated for non-model plants because they might have been recruited to specific developmental processes. PMID- 26846420 TI - Eliciting parental support for the use of newborn blood spots for pediatric research. AB - BACKGROUND: Biomarkers of exposures such as infection or environmental chemicals can be measured in small volumes of blood extracted from newborn dried blood spots (DBS) underscoring their potential utility for population-based research. However, few studies have evaluated the feasibility and utility of this resource; particularly the factors associated with parental consent, and the ability to retrieve banked samples with sufficient remaining volume for epidemiologic research. METHODS: At 8 months postpartum, 5,034 mothers of infants born (2008 2010) in New York (57 counties excluding New York City) were asked to consent for the use of residual DBS for the quantification of cytokines and environmental chemicals. Mothers were part of the Upstate KIDS study, a longitudinal birth cohort designed to evaluate child development through 3 years of age. Information on parental and infant characteristics was obtained from birth certificates and maternal report at 4 months postpartum. Multivariate logistic regression was used to identify factors associated with parental consent and with successful retrieval of DBS. RESULTS: Sixty-two percent (n = 3125) of parents consented. Factors significantly associated with consent included non-Hispanic ethnicity (odds ratio 2.04; 95% CI: 1.43-2.94), parity (1.29; 1.05-1.57), maternal obesity (1.42; 1.11-1.80) and reported alcohol use during pregnancy (1.51; 1.12-2.06). However, these associations corresponded to small absolute differences in proportions (4 to 8%), suggesting that the two groups remained comparable. Infant characteristics such as preterm delivery did not significantly differ by consent status among singletons and only ventilator use (OR 2.39; 95% CI: 1.06-5.41) remained borderline significant among twins in adjusted analyses. Among consented infants, 99% had at least one 3.2 mm punch successfully retrieved for biomarker analyses and 84% had a full DBS circle available. CONCLUSION: Parental characteristics varied slightly by consent, and the availability of samples for research purposes was high, demonstrating the feasibility of this resource for population based research. PMID- 26846422 TI - Professor Andre Jouve (1909-2001): A French cardiologist who was a pioneer of clinical vector-electrocardiography and cardiovascular epidemiology. AB - Andre, Julien, Auguste Jouve was born in Marseilles on June 10, 1909 son of Xavier Marie Francois Louis Jouve MD and Marie Louise Charlotte Vigliengo his wife. He had a brilliant medical career in Marseilles: Resident at Marseilles Hospitals in 1931, major of his promotion, then an Assistant in 1943 and a Chief in 1951, to become Associate Professor of Medicine in 1946 and finally Full Professor of Clinical and Experimental Cardiology in 1954. Fellow of several Cardiological Societies, he became President of the French Society of Cardiology in 1968, Vice-President of the European Society of Cardiology in 1972 and finally President of the French College of Vascular Pathology in 1973. He had been a WHO Expert for degenerative and cardiovascular diseases from 1958 to 1981 and a National correspondent of the Academy of Medicine in 1977. He was decorated by the Legion d'Honneur (Officer in 1975). He retired in 1981 and died in 2001. Clinical vector-electrocardiology and cardiovascular epidemiology were the main areas of his interest where he made essential contributions such as the famous treatise on ECG. The Heart Cantini Center was considered his leading creation and action, where the first French heart transplantation was performed in 1968, the first French epidemiological investigation on coronary risk factors took place, the idea of starting prevention at pediatric age was clearly outlined and the need of concentrating on psychological and dysmetabolic factors was precisely advocated for indexing later development of ischemic heart diseases. These achievements are reviewed and put into perspective. PMID- 26846421 TI - Multisubstance Use Among Treatment-Seeking Smokers: Synergistic Effects of Coping Motives for Cannabis and Alcohol Use and Social Anxiety/Depressive Symptoms. AB - OBJECTIVE: This study examined the impact of coping motives for cannabis and alcohol use on the relation between social anxiety/depressive symptoms and severity of substance use for alcohol, tobacco, and cannabis among treatment seeking smokers who also use cannabis and alcohol. METHODS: The sample included 197 daily cigarette smokers (MAge 34.81 years, SD = 13.43) who reported using cannabis and alcohol. RESULTS: Hierarchical multiple regression analyses were conducted wherein separate models were constructed for each dependent variable. Among individuals with higher social anxiety, alcohol coping motives were associated with heavier drinking, and this was more pronounced among those low in depressive symptoms. Similarly, those at greater risk for nicotine dependence were anxious individuals with lower depressive symptoms who endorse coping oriented motives for using cannabis. Further, among those with higher social anxiety, cannabis coping motives were associated with marginally greater drinking, particularly for those high in depressive symptoms. CONCLUSIONS: The present findings support the perspective that among multisubstance users, the interplay between social anxiety, depressive symptoms, and coping-oriented motives for using one substance (e.g., cannabis or alcohol) may pose difficulties in refraining from other substances (e.g., tobacco). This observation highlights the importance of tailoring multisubstance treatments to specific needs of multiusers for whom single-substance interventions may be less effective. Findings also support previous work exploring the benefits of concurrently treating co-occurring substance use and lend credence to the perspective that motivation to use substances for coping reasons is of central theoretical and clinical relevance. PMID- 26846423 TI - Mapping of Health Communication and Education Strategies Addressing the Public Health Dangers of Illicit Online Pharmacies. AB - Illicit online pharmacies are a growing global public health concern. Stakeholders have started to engage in health promotion activities to educate the public, yet their scope and impact has not been examined. We wished to identify health promotion activities focused on consumer awareness regarding the risks of illicit online pharmacies. Organizations engaged on the issue were first identified using a set of engagement criteria. We then reviewed these organizations for health promotion programs, educational components, public service announcements, and social media engagement. Our review identified 13 organizations across a wide spectrum of stakeholders. Of these organizations, 69.2% (n = 9) had at least one type of health promotion activity targeting consumers. Although the vast majority of these organizations were active on Facebook or Twitter, many did not have dedicated content regarding online pharmacies (Facebook: 45.5%, Twitter: 58.3%). An online survey administered to 6 respondents employed by organizations identified in this study found that all organizations had dedicated programs on the issue, but only half had media planning strategies in place to measure the effectiveness of their programs. Overall, our results indicate that though some organizations are actively engaged on the issue, communication and education initiatives have had questionable effectiveness in reaching the public. We note that only a few organizations offered comprehensive and dedicated content to raise awareness on the issue and were effective in social media communications. In response, more robust collaborative efforts between stakeholders are needed to educate and protect the consumer about this public health and patient safety danger. PMID- 26846425 TI - Implementation of team-based learning in year 1 of a PBL based medical program: a pilot study. AB - BACKGROUND: A traditional and effective form of teaching within medical education has been Problem Based Learning (PBL). However, this method of teaching is resource intensive, normally requiring one tutor for every ten students. Team based learning (TBL) has gained recent popularity in medical education, and can be applied to large groups of up to 100 students. TBL makes use of the advantages of small group teaching and learning, but in contrast to PBL, does not need large numbers of teachers. This study sought to explore the efficacy of using TBL in place of PBL in Year 1 of a medical program. METHODS: In Year 1 of the medical program, two iterations of TBL, with 20 students, were run following four iterations of PBL within the Cardiology teaching block. Student feedback following PBL and TBL was collected by questionnaire, using closed and open ended questions. Additionally, individual and team tests were held at the beginning of each TBL class, and results of each week were compared. RESULTS: All students (n = 20) participated in the test in week 1, and 18/20 students participated in week 2. In total, 19/20 (95%) of students completed the questionnaires regarding their PBL and TBL experiences. The use of small groups, the readiness assurance tests, immediate feedback from an expert clinician, as well as time efficiency were all aspects of the TBL experience that students found positive. The clinical problem solving activity, however, was considered to be less effective with TBL. There was a significant improvement (p = 0.004) in students' score from the week 1 assessment (median = 2) to the week 2 (median = 3.5) assessment. Interestingly, all teams but one (Team 1) achieved a lower score on their second week assessment than on their first. However, the lowest performing team in week 1 outperformed all other teams in week 2. CONCLUSION: Students favoured many aspects of the TBL process, particularly motivation to do the pre-reading, and better engagement in the process. Additionally, the application of TBL principles meant the sessions were not reliant upon a large teacher to student ratio. Students, however, highlighted the need for more time within TBL for clinical problem-solving. PMID- 26846424 TI - Socioeconomic and clinical factors explaining the risk of unstructured antiretroviral therapy interruptions among Kenyan adult patients. AB - A cross-sectional study was conducted to assess the extent of unstructured HIV treatment interruptions (TIs) and investigate the effects of socioeconomic, socio demographic, HIV treatment-related and clinical factors on the magnitude and rate of the same among adult patients at a Kenyan regional referral center. Four hundred and twenty-one adult patients actively receiving antiretroviral therapy at Nyeri County Referral Hospital since 2003 were randomly selected to complete a health survey questionnaire. Electronic records were used to obtain their HIV treatment utilization history. The marginal effects of selected determinants on prevalence and rate of TI were assessed by fitting multiple Poisson log-linear regression models. In total, 392 patients participated in the study. HIV TI was prevalent with 64.5% having had at least one TI of 3 months or more during treatment. The risk of TI was significantly higher in those longer on treatment (prevalence ratio = 1.2, 95% confidence interval [CI] 1.12-1.28). Greater risk of TI was also associated with lower income (prevalence rate ratio [PRR] = 0.9, 95% CI 0.83-1.00), low medication adherence (PRR = 0.3, 95% CI 0.13-0.72), inconsistent treatment engagement (PRR = 0.4, 95% CI 0.19-0.75) and, contrarily, fewer adverse drug reactions (PRR = 0.9, 95% CI 0.90-0.97). Unstructured HIV TIs appear to be fairly common at the study site. The results suggest that efforts to minimize HIV TI could benefit from treatment-continuity monitoring strategies that target the high-risk sub-samples identified. PMID- 26846426 TI - Verification of endotracheal tube placement using electrical stimulation through electrodes placed on the endotracheal tube cuff. AB - BACKGROUND: Current methods for verification of endotracheal intubation can fail, particularly in emergency settings. We investigated whether a verification method using electrical stimulation through electrodes placed on the endotracheal tube cuff could distinguish endotracheal and esophageal intubations in an experimental setting. METHODS: During three sequential sessions simulating emergency intubation without paralysis, rapid sequence intubation (RSI) with neuromuscular blockade, and intubation during cardiopulmonary resuscitation, eight pigs were intubated with an endotracheal tube fitted with two electrodes exposed on the cuff of the tube, first in the esophagus and next in the trachea or in reverse sequence. Cuff pressure was monitored during a 5-s electrical stimulation (20 mA, 80 Hz, 500 MUs), and delta pressure was calculated as the difference between baseline cuff pressure and maximum cuff pressure during the electrical stimulation. RESULTS: Delta pressure was significantly higher in esophageal than in tracheal placements in all three sequential sessions (86.0 [78.3-89.7] vs. 6.5 [2.0-7.9] mmHg, P = 0.001; 16.6 [13.2-22.8] vs. 0.8 [0.3-2.6] mmHg, P = 0.004; 66.1 [60.0-84.7] vs. 2.7 [0.7-9.7] mmHg, P = 0.001). The delta pressure did not overlap between tracheal and esophageal intubations except for the session simulating RSI with neuromuscular blockade, in which one of eight esophageal placements showed a delta pressure within the delta pressure range of tracheal placements. CONCLUSION: Electrical stimulation through electrodes placed on the endotracheal tube cuff produced remarkably greater increases in cuff pressure in esophageal intubations than in tracheal intubations in an experimental setting. PMID- 26846427 TI - Tetradecylthiopropionic acid induces hepatic mitochondrial dysfunction and steatosis, accompanied by increased plasma homocysteine in mice. AB - BACKGROUND: Hepatic mitochondrial dysfunction plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Methyl donor supplementation has been shown to alleviate NAFLD, connecting the condition to the one-carbon metabolism. Thus, the objective was to investigate regulation of homocysteine (Hcy) and metabolites along the choline oxidation pathway during induction of hepatic steatosis by the fatty acid analogue tetradecylthiopropionic acid (TTP), an inhibitor of mitochondrial fatty acid oxidation. METHODS: Mice were fed a control diet, or diets containing 0.3 %, 0.6 %, or 0.9 % (w/w) TTP for 14 days. Blood and liver samples were collected, enzyme activities and gene expression were analyzed in liver, lipid and fatty acid composition in liver and plasma, one-carbon metabolites, B-vitamin status, carnitine and acylcarnitines were analyzed in plasma. RESULTS: Liver mitochondrial fatty acid oxidation decreased by 40 % and steatosis was induced in a dose dependent manner; total lipids increased 1.6-fold in animals treated with 0.3 % TTP, 2-fold with 0.6 % TTP and 2.1 fold with 0.9 % TTP compared to control. The higher hepatic concentration of fatty acids was associated with shortening of carbon-length. Furthermore, the inhibited fatty acid oxidation led to a 30-fold decrease in plasma carnitine and 9.3-fold decrease in acetylcarnitine at the highest dose of TTP, whereas an accumulation of palmitoylcarnitine resulted. Compared to the control diet, TTP administration was associated with elevated plasma total Hcy (control: 7.2 +/- 0.3 umol/L, 0.9 % TTP: 30.5 +/- 5.9 umol/L) and 1.4-1.6 fold increase in the one-carbon metabolites betaine, dimethylglycine, sarcosine and glycine, accompanied by changes in gene expression of the different B-vitamin dependent pathways of Hcy and choline metabolism. A positive correlation between total Hcy and hepatic triacylglycerol resulted. CONCLUSIONS: The TTP-induced inhibition of mitochondrial fatty acid oxidation was not associated with increased hepatic oxidative stress or inflammation. Our data suggest a link between mitochondrial dysfunction and the methylation processes within the one carbon metabolism in mice. PMID- 26846428 TI - Paradoxical acclimation responses in the thermal performance of insect immunity. AB - Winter is accompanied by multiple stressors, and the interactions between cold and pathogen stress potentially determine the overwintering success of insects. Thus, it is necessary to explore the thermal performance of the insect immune system. We cold-acclimated spring field crickets, Gryllus veletis, to 6 degrees C for 7 days and measured the thermal performance of potential (lysozyme and phenoloxidase activity) and realised (bacterial clearance and melanisation) immune responses. Cold acclimation decreased the critical thermal minimum from 0.5 +/- 0.25 to -2.1 +/- 0.18 degrees C, and chill coma recovery time after 72 h at -2 degrees C from 16.8 +/- 4.9 to 5.2 +/- 2.0 min. Measures of both potential and realised immunity followed a typical thermal performance curve, decreasing with decreasing temperature. However, cold acclimation further decreased realised immunity at low, but not high, temperatures; effectively, immune activity became paradoxically specialised to higher temperatures. Thus, cold acclimation induced mismatched thermal responses between locomotor and immune systems, as well as within the immune system itself. We conclude that cold acclimation in insects appears to preferentially improve cold tolerance over whole-animal immune performance at low temperatures, and that the differential thermal performance of physiological responses to multiple pressures must be considered when predicting ectotherms' response to climate change. PMID- 26846429 TI - School-Based Interventions to Improve Cardiorespiratory Fitness in Adolescents: Systematic Review with Meta-analysis. AB - BACKGROUND: School-based intervention can contribute to the promotion of cardiorespiratory fitness (CRF) in adolescents. However, it is neces sary to systematize how intervention strategies and the methodological characteristics of studies influence the effects of CRF interventions. OBJECTIVE: A meta-analysis review of school-based intervention studies aimed at increasing CRF in adolescents (10-19 years of age) was conducted. METHODS: A search for studies was conducted using the Medline, Web of Science, LILACS, PsycINFO, Embase, Scopus, SPORTDiscus and Cochrane databases and the reference lists of the selected studies. The peer selection process included consideration of school-based randomized or non-randomized controlled trials with a duration >=12 weeks published in English, Portuguese or Spanish, and with some CRF measures. The methodological quality of the studies was also assessed. The standardized mean differences (SMDs) and 95 % confidence intervals (95 % CIs) were calculated as an effect measure. RESULTS: Forty publications of 30 interventions were included in the review, and 25 of these were meta-analysed. The effects of CRF interventions were moderate and significant (SMD = 0.68, 95 % CI 0.45-0.90), with high heterogeneity (I (2) = 97 %). The effect size varied significantly according to the age group, sample size, intervention environment, strategies in experimental groups, CRF priority in the study, CRF test and indicator, session length, weekly frequency, intervention duration and presentation of results by sex. CONCLUSION: Interventions in the school environment seem to have a positive effect on CRF among adolescents, but there is high heterogeneity between studies. Some intervention characteristics can explain better effects on CRF (e.g. exercise sessions in addition to physical education classes; primary focus on this outcome; combination of aerobic and resistance exercises; classes lasting >=60 min; frequency of three times weekly; and intensity control). PMID- 26846430 TI - Sport Injuries Sustained by Athletes with Disability: A Systematic Review. AB - BACKGROUND: Fifteen percent of the world's population live with disability, and many of these individuals choose to play sport. There are barriers to sport participation for athletes with disability and sports injury can greatly impact on daily life, which makes sports injury prevention additionally important. OBJECTIVE: The purpose of this review is to systematically review the definitions, methodologies and injury rates in disability sport, which should assist future identification of risk factors and development of injury prevention strategies. A secondary aim is to highlight the most pressing issues for improvement of the quality of injury epidemiology research for disability sport. METHODS: A search of NICE, AMED, British Nursing Index, CINAHL, EMBASE and Medline was conducted to identify all publications up to 16 June 2015. Of 489 potentially relevant articles and reference searching, a total of 15 studies were included. Wide study sample heterogeneity prevented data pooling and meta analysis. RESULTS: Results demonstrated an evolving field of epidemiology, but with wide differences in sports injury definition and with studies focused on short competitions. Background data were generally sparse; there was minimal exposure analysis, and no analysis of injury severity, all of which made comparison of injury risk and injury severity difficult. CONCLUSION: There is an urgent need for consensus on sports injury definition and methodology in disability sports. The quality of studies is variable, with inconsistent sports injury definitions, methodologies and injury rates, which prevents comparison, conclusions and development of injury prevention strategies. The authors highlight the most pressing issues for improvement of the quality in injury epidemiology research for disability sport. PMID- 26846433 TI - Effect of alcohol consumption on peripheral blood Alu methylation in Korean men. AB - Alcohol use disorders (AUD) are defined as alcohol abuse and alcohol dependence, which create a substantial public health problem worldwide. To date, no therapeutic can effectively solve these problems. They are complex diseases characterized by both genetic and environmental factors. DNA methylation can act as a downstream effector of environmental signals and account for multi-factorial nature of the disease. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Alu elements host one-quarter of CpG dinucelotides in the genome to function as proxies for global DNA methylation. In this study, we evaluated the Alu methylation in the peripheral blood DNA of healthy volunteers and AUD patients using the pyrosequencing technology. The Alu methylation level is significantly higher in AUD compared to healthy controls (23.4 +/- 1.6 versus 22.1 +/- 1.0, t = 7.83, p < 0.0001). Moreover, significant correlation was found between Alu methylation and alcohol use disorders identification test score (r = 0.250, p < 0.0001), alcohol problem (r = 0.294, p < 0.0001), and life position (r = -0.205, p = 0.0005). Overall, these novel findings indicate that alcohol-related increase in Alu methylation might play a complex role in the etiology and pathogenesis of AUD. Further studies are required to elucidate the mechanisms underlying this relationship. PMID- 26846432 TI - Age-dependent changes in the protein expression levels of Redd1 and mTOR in the gerbil hippocampus during normal aging. AB - Redd1, also known as RTP801/Dig2/DDIT4, is a stress-induced protein and a negative regulator of mammalian target of rapamycin (mTOR). Redd1 is also closely associated with oxidative stress and DNA damage. In the present study, age related changes in the protein expression levels of mTOR and Redd1 were investigated using immunohistochemistry and western blot in the gerbil hippocampus at postnatal month (PM) 3, 6, 12 and 24. No significant differences were identified in the levels of mTOR among the experimental groups, whereas, the levels of phosphorylated mTOR decreased with age. The protein expression levels of Redd1 were observed to gradually increase with age; in the PM 24 group, the level was significantly increased (~189.2%), compared with the PM 3 group. In addition, Redd1 immunoreactivity was significantly increased in the hippocampal principal neurons of the PM 24 group, including the pyramidal cells in the hippocampus proper and granule cells in the dentate gyrus, compared with the other experimental groups. These results demonstrated that the protein expression of Redd1 in the hippocampus was markedly increased during normal aging, indicating that the age-related increase in the expression of Redd1 may be closely associated with age-related hippocampal change. PMID- 26846434 TI - Nanoparticle Decorated Ultrathin Porous Nanosheets as Hierarchical Co3O4 Nanostructures for Lithium Ion Battery Anode Materials. AB - We report a facile synthesis of a novel cobalt oxide (Co3O4) hierarchical nanostructure, in which crystalline core-amorphous shell Co3O4 nanoparticles with a bimodal size distribution are uniformly dispersed on ultrathin Co3O4 nanosheets. When tested as anode materials for lithium ion batteries, the as prepared Co3O4 hierarchical electrodes delivered high lithium storage properties comparing to the other Co3O4 nanostructures, including a high reversible capacity of 1053.1 mAhg(-1) after 50 cycles at a current density of 0.2 C (1 C = 890 mAg( 1)), good cycling stability and rate capability. PMID- 26846435 TI - Visual acuity loss in patients with age-related macular degeneration measured using a novel high-pass letter chart. AB - BACKGROUND/AIMS: Conventional Logarithm of the Minimum Angle of Resolution (logMAR) acuity is the current gold standard for assessing visual function in age related macular degeneration (AMD). However, visual acuity (VA) often remains 'normal' when measured with these charts, even with advanced retinal changes. We wished to investigate how VA measurements with the Moorfields Acuity Chart (MAC), which employs high-pass filtered letters, compares to conventional letter charts in subjects with AMD. METHODS: Monocular best-corrected VA measurements and test retest variability (TRV) were compared for conventional and MAC charts in 38 normal observers (mean age 52.1 years) and 80 patients (mean age 80.6 years) with varying degrees of acuity loss owing to AMD. Methods of Bland-Altman and ordinary least-squares regression were employed for data analysis. RESULTS: A proportional bias was confirmed between conventional and MAC measurements (r(2)=0.133, p=0.001) such that MAC acuity was -0.45 logMAR 'worse' at the 0.00 logMAR acuity level, but only -0.26 logMAR 'worse' at the 1.00 logMAR level. The mean bias was much smaller in the normal subject group (-0.16 logMAR). Similar TRV (ranging from +/-0.09 to +/-0.12 logMAR) was found for both charts in both subject groups. CONCLUSIONS: VA measurements with the MAC chart appear to be more sensitive to functional loss in AMD compared with conventional letter charts, with similar TRV. Simulations indicate this may be because the high-pass filtered letters are more vulnerable to undersampling as a result of retinal cell loss in the disease process. PMID- 26846436 TI - Catalytic insertion of aldehydes into dihalonitroacetophenones via sequential bond scission-aldol reaction-acyl transfer. AB - A catalytic process that provides dihalogenated nitro alcohols in up to 99% yield and with 100% atom economy is described. In situ cleavage of dihalonitroacetophenones affords nitronates that undergo Lewis acid catalyzed addition to aldehydes. Final benzoylation renders the sequence irreversible and regenerates the bond scission and acyl transfer agent. PMID- 26846437 TI - Controlled gelation kinetics of cucurbit[7]uril-adamantane cross-linked supramolecular hydrogels with competing guest molecules. AB - Gelation kinetics of hydrogels is closely linked to many applications such as the development of injectable and printable hydrogels. However, the control of gelation kinetics without compromising the structure and other properties of the hydrogels, remains a challenge. Here, we demonstrate a method to control the gelation kinetics of cucurbit[7]uril-adamantane (CB[7]-AD) cross-linked supramolecular hydrogels by using competing guest molecules. The association between CB[7] and AD moieties on the polymer backbone was impeded by pre occupying the CB[7] cavity with competing guest molecules. By using various guest molecules and concentrations, the gelation of the hydrogels could be varied from seconds to hours. The strong interaction of CB[7]-AD pair endue the hydrogels good mechanical properties and stability. Moreover, the binding of functionalized guest molecules of CB[7] moieties offers a facile approach for tailoring of the hydrogels' scaffold. Combined with hydrogel injection and printing technology, this method offers an approach for the development of hydrogels with advanced temporal and spatial complexity. PMID- 26846438 TI - A randomised controlled trial of supplemental oxygen versus medical air during exercise training in people with chronic obstructive pulmonary disease: supplemental oxygen in pulmonary rehabilitation trial (SuppORT) (Protocol). AB - BACKGROUND: Oxygen desaturation during exercise is common in people with chronic obstructive pulmonary disease (COPD). The aim of the study is to determine, in people with COPD who desaturate during exercise, whether supplemental oxygen during an eight-week exercise training program is more effective than medical air (sham intervention) in improving exercise capacity and health-related quality of life both at the completion of training and at six-month follow up. METHODS/DESIGN: This is a multi-centre randomised controlled trial with concealed allocation, blinding of participants, exercise trainers and assessors, and intention-to-treat analysis. 110 people with chronic obstructive pulmonary disease who demonstrate oxygen desaturation lower than 90 % during the six-minute walk test will be recruited from pulmonary rehabilitation programs in seven teaching hospitals in Australia. People with chronic obstructive pulmonary disease on long term oxygen therapy will be excluded. After confirmation of eligibility and baseline assessment, participants will be randomised to receive either supplemental oxygen or medical air during an eight-week supervised treadmill and cycle exercise training program, three times per week for eight weeks, in hospital outpatient settings. Primary outcome measures will be endurance walking capacity assessed by the endurance shuttle walk test and health related quality of life assessed by the Chronic Respiratory Disease Questionnaire. Secondary outcomes will include peak walking capacity measured by the incremental shuttle walk test, dyspnoea via the Dyspnoea-12 questionnaire and physical activity levels measured over seven days using an activity monitor. All outcomes will be measured at baseline, completion of training and at six-month follow up. DISCUSSION: Exercise training is an essential component of pulmonary rehabilitation for people with COPD. This study will determine whether supplemental oxygen during exercise training is more effective than medical air in improving exercise capacity and health-related quality of life in people with COPD who desaturate during exercise. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000395831, 5th Jan,2012. PMID- 26846439 TI - Abnormal villous morphology mimicking a hydatidiform mole associated with paternal trisomy of chromosomes 3,7,8 and unipaternal disomy of chromosome 11. AB - BACKGROUND: Pregnancies affected by non-molar chromosomal abnormality may sometimes demonstrate abnormal chorionic villous morphology that is similar to partial hydatidiform mole. Determination of the underlying aetiology may be difficult in such cases. CASE PRESENTATION: This report describes a case referred to the regional trophoblastic disease unit as a possible hydatidiform mole that demonstrated both villous dysmorphology and abnormal p57(KIP2) expression. Molecular genotyping revealed that while most chromosomes in the villous tissue were diploid and biparental, chromosomes 3, 7 and 8 were trisomic with an additional paternally derived chromosome. In contrast chromosome 11 showed uniparental disomy of paternal origin a situation more usually associated with complete hydatidiform moles. This unusual case highlights that exceptions may occur to the general rules of both histological morphology and immunoprofile, and that these can be resolved by detailed molecular genetic investigations. CONCLUSION: The findings confirm that trisomic pregnancies may demonstrate morphological villous features similar to hydatidiform mole, and that loss of p57(KIP2) expression occurs due to an absence of maternally transcribed genes on chromosome 11 and can therefore be independent of androgenetic complete hydatidiform mole. PMID- 26846441 TI - "No small talk please, my baby's just died". PMID- 26846440 TI - Barriers and facilitators to the implementation of orthodontic mini-implants in clinical practice: a protocol for a systematic review and meta-analysis. AB - BACKGROUND: Most orthodontic treatment plans need some form of anchorage to control the reciprocal forces of tooth movement. Orthodontic mini implants (OMIs) have been hailed for having revolutionized orthodontics, because they provide anchorage without depending on the collaboration of patients, they have a favorable effectiveness compared with conventional anchorage devices, and they can be used for a wide scale of treatment objectives. However, surveys have shown that many orthodontists never or rarely use them. To understand the rationale behind this knowledge-to-action gap, we will conduct a systematic review that will identify and quantify potential barriers and facilitators to the implementation of OMIs in clinical practice for all potential stakeholders, i.e., patients, family members, clinicians, office staff, clinic owners, policy makers, etc. The prevalence of clinicians that do not use OMIs will be our secondary outcome. METHODS: The Preferred Reporting Items for Systematic review and Meta Analysis Protocols (PRISMA-P) 2015 Statement was adopted as the framework for reporting this manuscript. We will apply broad-spectrum search strategies and will search MEDLINE and more than 40 other databases. We will conduct searches in the gray literature, screen reference lists, and hand-search 12 journals. All study designs, stakeholders, interventions, settings, and languages will be eligible. We will search studies that report on barriers or facilitators to the implementation of orthodontic mini implants (OMIs) in clinical practice. Implementation constructs and their prevalence among pertinent stakeholders will be our primary outcomes. All searching and data extraction procedures will be conducted by three experienced reviewers. We will also contact authors and investigators to obtain additional information on data items and unidentified studies. Risk of bias will be scored with tools designed for the specific study designs. We will assess heterogeneity, meta-biases, and the robustness of the overall evidence of outcomes. We will present findings in a systematic narrative synthesis and plan meta-analyses when pertinent criteria are met. DISCUSSION: Knowledge creation on this research topic could identify and quantify both expected and unexpected implementation constructs and their stakeholders. Such knowledge can help develop strategies to address implementation issues and redirect future studies on OMIs towards knowledge translation. This could lead to improved patient-health experiences and a reduction in research waste. PMID- 26846442 TI - Treatment of complex aortic aneurysms with fenestrated endografts and chimney stent repair: Systematic review and meta-analysis. AB - Objective We reviewed data pertaining to fenestrated endograft technique and chimney stent repair of complex aortic aneurysm for comparative analysis of the outcomes. Methods A comprehensive search of relevant databases was conducted to identify articles in English, related to the treatment of complex aortic aneurysm with fenestrated endovascular aneurysm repair and chimney stent repair, published until January 2015. Results A total of 42 relevant studies and 2264 patients with aortic aneurysm undergoing fenestrated endovascular aneurysm repair and chimney stent repair were included in our review. A total of 4413 vessels were involved in these processes. The cumulative 30-day mortality was 2.4% and 3.2% ( p = 0.459). The follow-up aneurysm-related mortality was 1.4% and 3.2% ( p = 0.018), and target organ dysfunction was 5.0% and 4.0% in fenestrated endovascular aneurysm repair and chimney stent repair, respectively ( p = 0.27). A total of 156 vessels showed restenosis or occlusion after primary intervention (3.6% and 3.4% in fenestrated endovascular aneurysm repair and chimney stent repair, respectively, p = 0.792). The cumulative type I endoleak was 2.0% (38/1884) after fenestrated endovascular aneurysm repair compared with 3.4% (13/380) after chimney stent repair ( p = 0.092), and the type II endoleak was 5.4% (102/1884) and 5.3% (20/380), respectively ( p = 0.905). Approximately, 1.1% and 1.6% increase in aneurysm was observed following fenestrated endovascular aneurysm repair and chimney stent repair, respectively ( p = 0.437). The re-intervention frequency was 205 and 19 cases after fenestrated endovascular aneurysm repair and chimney stent repair, respectively (11.7%, 5.6%, p = 0.001). Conclusions Fenestrated endovascular aneurysm repair and chimney stent repair are safe and effective in treating patients with complex aortic aneurysm. A higher aneurysm related mortality was observed in chimney stent repair while fenestrated endovascular aneurysm repair was associated with a higher re-intervention rate. PMID- 26846444 TI - Non-adiabatic holonomic quantum computation in linear system-bath coupling. AB - Non-adiabatic holonomic quantum computation in decoherence-free subspaces protects quantum information from control imprecisions and decoherence. For the non-collective decoherence that each qubit has its own bath, we show the implementations of two non-commutable holonomic single-qubit gates and one holonomic nontrivial two-qubit gate that compose a universal set of non-adiabatic holonomic quantum gates in decoherence-free-subspaces of the decoupling group, with an encoding rate of (N - 2)/N. The proposed scheme is robust against control imprecisions and the non-collective decoherence, and its non-adiabatic property ensures less operation time. We demonstrate that our proposed scheme can be realized by utilizing only two-qubit interactions rather than many-qubit interactions. Our results reduce the complexity of practical implementation of holonomic quantum computation in experiments. We also discuss the physical implementation of our scheme in coupled microcavities. PMID- 26846445 TI - Luminescent organoboron ladder compounds via directed electrophilic aromatic C-H borylation. AB - Luminescent B-N containing conjugated ladder compounds are prepared by directed electrophilic aromatic substitution. Negishi cross-coupling reaction of 2,7 dibromo-9,9-dihexylfluorene with 6-methylpyridin-2-yl(pivaloyloxy)zinc furnishes the dipyridylfluorene precursor (1) in 44% yield. Compound 1 is then subjected to electrophilic borylation with BBr3 in the presence of iPr2NEt as a bulky base to give the tetra-coordinate ladder-type organoboron species 2-Br. Arylation of 2-Br is accomplished by addition of Ph2Zn or C6F5Cu in toluene furnishing the targeted bis(pentafluorophenyl)borane and diphenylborane species 2-Ar (Ar = Ph, C6F5) in 53 and 44% yield respectively. The products show a strong blue emission and undergo multi-step reversible reduction and oxidation processes. The effect of fluorination of the pendant aryl groups on the electronic structure is further examined by DFT methods. PMID- 26846443 TI - The Method for Performance Measurement Matters: Diabetes Care Quality as Measured by Administrative Claims and Institutional Registry. AB - OBJECTIVES: Performance measurement is used by health care providers, payers, and patients. Historically accomplished using administrative data, registries are used increasingly to track and improve care. We assess how measured diabetes care quality differs when calculated using claims versus registry. DATA SOURCES/STUDY SETTING: Cross-sectional analysis of administrative claims and electronic health records (EHRs) of patients in a multispecialty integrated health system in 2012 (n = 368,883). STUDY DESIGN: We calculated percent of patients attaining glycohemoglobin <8.0 percent, LDL cholesterol <100 mg/dL, blood pressure <140/90 mmHg, and nonsmoking (D4) in cohorts, identified by Medicare Accountable Care Organization/Minnesota Community Measures (ACO-MNCM; claims-based), Healthcare Effectiveness Data and Information Set (HEDIS; claims-based), and registry (EHR based). DATA COLLECTION/EXTRACTION METHODS: Claims were linked to EHR to create a dataset of performance-eligible patients. PRINCIPAL FINDINGS: ACO-MNCM, HEDIS, and registry identified 6,475, 6,989, and 6,425 measurement-eligible patients. Half were common among the methods; discrepancies were due to attribution, age restriction, and encounter requirements. D4 attainment was lower in ACO-MNCM (36.09 percent) and HEDIS (37.51 percent) compared to registry (43.74 percent) cohorts. CONCLUSIONS: Registry- and claims-based performance measurement methods identify different patients, resulting in different rates of quality metric attainment with implications for innovative population health management. PMID- 26846446 TI - Effectiveness of Pharmacist-Led Amiodarone Monitoring Services on Improving Adherence to Amiodarone Monitoring Recommendations: A Systematic Review. AB - Amiodarone remains the mostly frequently used antiarrhythmic in clinical practice and is most often used to maintain normal sinus rhythm in patients with atrial fibrillation who have failed a rate control strategy. Amiodarone has superior efficacy over other antiarrhythmics, a lower risk of torsade de pointes, and a better cardiovascular safety profile in patients with structural heart disease. However, amiodarone is associated with notable noncardiac toxicities affecting the thyroid, lungs, eyes, liver, and central nervous system. Since 2000, clinicians have been advised to follow amiodarone monitoring guidelines provided by the Heart Rhythm Society. Adherence to these recommendations in clinical practice, however, is suboptimal. Pharmacists play a major role in ensuring the safe and effective use of medications, particularly high-risk medications such as amiodarone. This qualitative review details the evidence supporting the role of pharmacist-led amiodarone monitoring services (AMS) in improving adherence to amiodarone monitoring guidelines and identifying adverse effects. Five studies were identified, and, overall, these programs had a favorable impact on improving adherence to guideline-recommended monitoring standards for amiodarone. The available evidence is limited by the significant variations in study designs and outcome definitions, lack of patient randomization, and limited generalizability. Nevertheless, available studies suggest that pharmacist-led AMS may improve adherence to recommended monitoring guidelines and identification of amiodarone related adverse effects. Further study is warranted to demonstrate whether these services impact the overall quality of care provided to patients receiving amiodarone, which may justify broader implementation. PMID- 26846447 TI - Identification of a de novo DYNC1H1 mutation via WES according to published guidelines. AB - De novo mutations that contribute to rare Mendelian diseases, including neurological disorders, have been recently identified. Whole-exome sequencing (WES) has become a powerful tool for the identification of inherited and de novo mutations in Mendelian diseases. Two important guidelines were recently published regarding the investigation of causality of sequence variant in human disease and the interpretation of novel variants identified in human genome sequences. In this study, a family with supposed movement disorders was sequenced via WES (including the proband and her unaffected parents), and a standard investigation and interpretation of the identified variants was performed according to the published guidelines. We identified a novel de novo mutation (c.2327C > T, p.P776L) in DYNC1H1 gene and confirmed that it was the causal variant. The phenotype of the affected twins included delayed motor milestones, pes cavus, lower limb weakness and atrophy, and a waddling gait. Electromyographic (EMG) recordings revealed typical signs of chronic denervation. Our study demonstrates the power of WES to discover the de novo mutations associated with a neurological disease on the whole exome scale, and guidelines to conduct WES studies and interpret of identified variants are a preferable option for the exploration of the pathogenesis of rare neurological disorders. PMID- 26846449 TI - Experiences with a voluntary surveillance system for early detection of equine diseases in Switzerland. AB - Clinical observations made by practitioners and reported using web- and mobile based technologies may benefit disease surveillance by improving the timeliness of outbreak detection. Equinella is a voluntary electronic reporting and information system established for the early detection of infectious equine diseases in Switzerland. Sentinel veterinary practitioners have been able to report cases of non-notifiable diseases and clinical symptoms to an internet based platform since November 2013. Telephone interviews were carried out during the first year to understand the motivating and constraining factors affecting voluntary reporting and the use of mobile devices in a sentinel network. We found that non-monetary incentives attract sentinel practitioners; however, insufficient understanding of the reporting system and of its relevance, as well as concerns over the electronic dissemination of health data were identified as potential challenges to sustainable reporting. Many practitioners are not yet aware of the advantages of mobile-based surveillance and may require some time to become accustomed to novel reporting methods. Finally, our study highlights the need for continued information feedback loops within voluntary sentinel networks. PMID- 26846450 TI - Engineering therapeutic antibodies targeting G-protein-coupled receptors. AB - G-protein-coupled receptors (GPCRs) are one of the most attractive therapeutic target classes because of their critical roles in intracellular signaling and their clinical relevance to a variety of diseases, including cancer, infection and inflammation. However, high conformational variability, the small exposed area of extracellular epitopes and difficulty in the preparation of GPCR antigens have delayed both the isolation of therapeutic anti-GPCR antibodies as well as studies on the structure, function and biochemical mechanisms of GPCRs. To overcome the challenges in generating highly specific anti-GPCR antibodies with enhanced efficacy and safety, various forms of antigens have been successfully designed and employed for screening with newly emerged systems based on laboratory animal immunization and high-throughput-directed evolution. PMID- 26846448 TI - Advances in understanding erythropoiesis: evolving perspectives. AB - Red blood cells (RBCs) are generated from haematopoietic stem and progenitor cells (HSPCs) through the step-wise process of differentiation known as erythropoiesis. In this review, we discuss our current understanding of erythropoiesis and highlight recent advances in this field. During embryonic development, erythropoiesis occurs in three distinct waves comprising first, the yolk sac-derived primitive RBCs, followed sequentially by the erythro-myeloid progenitor (EMP) and HSPC-derived definitive RBCs. Recent work has highlighted the complexity and variability that may exist in the hierarchical arrangement of progenitors responsible for erythropoiesis. Using recently defined cell surface markers, it is now possible to enrich for erythroid progenitors and precursors to a much greater extent than has been possible before. While a great deal of knowledge has been gained on erythropoiesis from model organisms, our understanding of this process is currently being refined through human genetic studies. Genes mutated in erythroid disorders can now be identified more rapidly by the use of next-generation sequencing techniques. Genome-wide association studies on erythroid traits in healthy populations have also revealed new modulators of erythropoiesis. All of these recent developments have significant promise not only for increasing our understanding of erythropoiesis, but also for improving our ability to intervene when RBC production is perturbed in disease. PMID- 26846453 TI - Alzheimer disease: A virtual Morris maze to assess cognitive impairment in Alzheimer disease. PMID- 26846451 TI - 16S rRNA gene-based metagenomic analysis reveals differences in bacteria-derived extracellular vesicles in the urine of pregnant and non-pregnant women. AB - Recent evidence has indicated that bacteria-derived extracellular vesicles (EVs) are important for host-microbe communication. The aims of the present study were to evaluate whether bacteria-derived EVs are excreted via the urinary tract and to compare the composition of bacteria-derived EVs in the urine of pregnant and non-pregnant women. Seventy-three non-pregnant and seventy-four pregnant women were enrolled from Dankook University and Ewha Womans University hospitals. DNA was extracted from urine EVs after EV isolation using the differential centrifugation method. 16S ribosomal RNA (16S rRNA) gene sequencing was performed using high-throughput 454 pyrosequencing after amplification of the V1-V3 region of the 16S rDNA. The composition of 13 taxa differed significantly between the pregnant and non-pregnant women. At the genus level, Bacillus spp. EVs were more significantly enriched in the urine of the pregnant women than in that of the non pregnant women (45.61% vs 0.12%, respectively). However, Pseudomonas spp. EVs were more dominant in non-pregnant women than in pregnant women (13.2% vs 4.09%, respectively). Regarding the compositional difference between pregnant women with normal and preterm delivery, EVs derived from Ureaplasma spp. and the family Veillonellaceae (including Megasphaera spp.) were more abundant in the urine of preterm-delivered women than in that of women with normal deliveries. Taken together, these data showed that Bacillus spp. EVs predominate in the urine of pregnant women, whereas Pseudomonas spp. EVs predominate in the urine of non pregnant women; this suggests that Bacillus spp. EVs might have an important role in the maintenance of pregnancy. PMID- 26846454 TI - Traumatic brain injury: Soluble sensors successful in rats. PMID- 26846455 TI - Demyelinating disease: NMO spectrum disorders: clinical or molecular classification? PMID- 26846452 TI - Characterization of the aodA, dnmA, mnSOD and pimA genes in Aspergillus nidulans. AB - Mitochondria play key roles in cellular energy generation and lifespan of most eukaryotes. To understand the functions of four nuclear-encoded genes predicted to be related to the maintenance of mitochondrial morphology and function in Aspergillus nidulans, systematic characterization was carried out. The deletion and overexpression mutants of aodA, dnmA, mnSOD and pimA encoding alternative oxidase, dynamin related protein, manganese superoxide dismutase and Lon protease, respectively, were generated and examined for their growth, stress tolerances, respiration, autolysis, cell death, sterigmatocystin production, hyphal morphology and size, and mitochondrial superoxide production as well as development. Overall, genetic manipulation of these genes had less effect on cellular physiology and ageing in A. nidulans than that of their homologs in another fungus Podospora anserina with a well-characterized senescence. The observed interspecial phenotypic differences can be explained by the dissimilar intrinsic stabilities of the mitochondrial genomes in A. nidulans and P. anserina. Furthermore, the marginally altered phenotypes observed in A. nidulans mutants indicate the presence of effective compensatory mechanisms for the complex networks of mitochondrial defense and quality control. Importantly, these findings can be useful for developing novel platforms for heterologous protein production, or on new biocontrol and bioremediation technologies based on Aspergillus species. PMID- 26846456 TI - The Impact of Spinal Cord Stimulation on Sleep Patterns. AB - BACKGROUND: Studies of chronic pain show sleep disturbances to be a prevalent symptom in 50-88% of patients and studies show improved pain to correspond with improved sleep. The impact of spinal cord stimulation (SCS) on sleep in failed back surgery syndrome, complex regional pain syndrome, and neuropathic pain patients has not been studied prospectively. OBJECTIVES: We prospectively assess the impact of SCS on sleep quality using the Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS). Further we examine the correlations between sleep and pain. METHODS: Patients who underwent permanent SCS implantation completed six validated questionnaires to compare sleep patterns, pain intensity, and quality of life at baseline and six months postoperatively. Results were analyzed via paired samples t-tests and bivariate analysis. RESULTS: Data from 27 patients were collected. We saw a significant decrease in ISI scores (n = 23, t(df)=2.9(22), p = 0.008), and noted a trend in the percentage improvement between ISI and ESS (n = 12, t(df)=2.0(10), p = 0.078). We did not see any significant improvement in ESS. However, improvements in insomnia correlated with pain intensity as measured through visual analog scale score and McGill Pain Questionnaire (R = 0.546, p = 0.007 and R = 0.559, p = 0.006, respectively). DISCUSSION: We demonstrate that insomnia scores on ISI improve with SCS at six month follow-up. Further, we find that improvements in pain correlate with these ISI improvements. PMID- 26846457 TI - Challenges in preclinical to clinical translation for anticancer carrier-mediated agents. AB - Major advances in carrier-mediated agents (CMAs), which include nanoparticles and conjugates, have revolutionized drug delivery capabilities over the past decade. While providing numerous advantages over their small-molecule counterparts, there is substantial variability in how individual CMA formulations and patient characteristics affect the pharmacology, pharmacokinetics (PK), and pharmacodynamics (PD) (efficacy and toxicity) of these agents. Development or selection of animal models is used to predict the effects within a particular human disease. A breadth of studies have begun to emphasize the importance of preclinical animal models in understanding and evaluating the interaction between CMAs and the immune system and tumor matrix, which ultimately influences CMA PK (clearance and distribution) and PD (efficacy and toxicity). It is fundamental to study representative preclinical tumor models that recapitulate patients with diseases (e.g., cancer) and evaluate the interplay between CMAs and the immune system, including the mononuclear phagocyte system (MPS), chemokines, hormones, and other immune modulators. Furthermore, standard allometric scaling using body weight does not accurately predict drug clearance in humans. Future studies are warranted to better understand the complex pharmacology and interaction of CMA carriers within individual preclinical models and their biological systems, such as the MPS and tumor microenvironment, and their application to allometric scaling across species. WIREs Nanomed Nanobiotechnol 2016, 8:642-653. doi: 10.1002/wnan.1394 For further resources related to this article, please visit the WIREs website. PMID- 26846458 TI - Recurrent bacteremia with different strains of Streptococcus pyogenes in an immunocompromised child. AB - We report an immunocompromised child who experienced two episodes of bacteremia due to Streptococcus pyogenes. Random amplification of polymorphic DNA profiles, emm genotypes, superantigen profiles, antimicrobial susceptibility, and resistance-related genes were investigated, and the results showed different profiles between the two isolates. This is the first report describing recurrent bacteremia caused by different strains of S. pyogenes. PMID- 26846459 TI - Single-Laboratory Validation Study of a Method for Screening and Identification of Phosphodiesterase Type 5 Inhibitors in Dietary Ingredients and Supplements Using Liquid Chromatography/Quadrupole-Orbital Ion Trap Mass Spectrometry: First Action 2015.12. AB - A single-laboratory validation study of a method for screening and identification of phosphodiesterase type 5 (PDE5) inhibitors in dietary ingredients and supplements is described. PDE5 inhibitors were extracted from the samples using a 50:50 (v/v) mixture of acetonitrile and water and centrifuged. Supernatant was diluted, filtered, and analyzed by LC-high-resolution MS. Data were collected in MS acquisition mode that combined full-scan MS experiment with all-ion fragmentation and data-dependent MS/MS product from the ion scan experiment. This approach enabled collection of MS and tandem MS (MS/MS) data for both targeted and nontargeted PDE5 inhibitors in a single chromatographic run. Software facilitated identification of targeted analytes was performed based on the retention time, accurate mass, and isotopic pattern of pseudomolecular ions, and accurate masses of fragment ions using an in-house compound database. Detection and identification of other PDE5 inhibitors and novel analogs were performed by retrospective evaluation of MS and MS/MS experimental data. The method validation results obtained for evaluated matrixes fulfilled the probability of identification requirements and probability of detection requirements (for the pooled data) set at 90% (95% confidence interval) in the respective AOAC Standard Method Performance Requirements for identification and screening methods for PDE5 inhibitors. Limited data demonstrating the quantification capability of the method were also generated. Mean recovery and repeatability obtained for the evaluated PDE5 inhibitors were in the range 69-90% and 0.4-1.8%, respectively. PMID- 26846460 TI - The S1-S2 linker determines the distinct pH sensitivity between ZmK2.1 and KAT1. AB - Efficient stomatal opening requires activation of KAT-type K(+) channels, which mediate K(+) influx into guard cells. Most KAT-type channels are functionally facilitated by extracellular acidification. However, despite sequence and structural homologies, the maize counterpart of Arabidopsis KAT1 (ZmK2.1) is resistant to pH activation. To understand the structural determinant that results in the differential pH activation of these counterparts, we analysed chimeric channels and channels with point mutations for ZmK2.1 and its closest Arabidopsis homologue KAT1. Exchange of the S1-S2 linkers altered the pH sensitivity between the two channels, suggesting that the S1-S2 linker is essentially involved in the pH sensitivity. The effects of D92 mutation within the linker motif together with substitution of the first half of the linker largely resemble the effects of substitution of the complete linker. Topological modelling predicts that one of the two cysteines located on the outer face section of the S5 domain may serve as a potential titratable group that interacts with the S1-S2 linker. The difference between ZmK2.1 and KAT1 is predicted to be the result of the distance of the stabilized linkers from the titratable group. In KAT1, residue K85 within the linker forms a hydrogen bond with C211 that enables the pH activation; conversely, the linker of ZmK2.1 is distantly located and thus does not interact with the equivalent titration group (C208). Thus, in addition to the known structural contributors to the proton activation of KAT channels, we have uncovered a previously unidentified component that is strongly involved in this complex proton activation network. PMID- 26846461 TI - HLA-A, HLA-B, HLA-DRB1 allele and haplotype frequencies of 14,529 Chinese Han bone marrow donors living in Dalian, China. AB - We investigated the allele and haplotype frequencies of HLA-A, HLA-B and HLA-DRB1 loci in Dalian Chinese Han population using blood samples of unrelated marrow donors who live in Dalian. The genetic relationship between Dalian and different regions worldwide was further explored based on HLA status of different populations. A total of 14,529 samples were genotyped at 2-digit level only by sequence-specific oligonucleotide and sequence-based typing methods. Allele frequencies of HLA-A, HLA-B and HLA-DRB1 were calculated by the direct counting method. Haplotype frequencies and linkage disequilibrium (LD) values were calculated by the maximum likelihood method. F(ST) values were calculated by allele frequency data of each locus. Phylogeny tree of Nei's DA genetic distances was constructed by the UPGMA method. HLA-A*02 was the most frequent allele at HLA A locus followed by A*11 and A*24. Alleles at HLA-B locus ranked in decreasing order by frequency were B*40, B*15 and B*13. The three highest frequency alleles were DRB1*15, DRB1*09 and DRB1*12 at HLA-DRB1 locus. A*30-B*13-DRB1*07 was the most frequent three-locus haplotype. For the population relationships, Dalian had a relative close genetic relationship with Liaoning and Yantai-Weihai and a relative distant genetic relationship with Australia. The information obtained in this study may provide useful information for anthropological studies, for disease-association studies and helping bone marrow transplantation patients to search HLA-matched donors. PMID- 26846462 TI - Riboregulation of bacterial and archaeal transposition. AB - The coexistence of transposons with their hosts depends largely on transposition levels being tightly regulated to limit the mutagenic burden associated with frequent transposition. For 'DNA-based' (class II) bacterial transposons there is growing evidence that regulation through small noncoding RNAs and/or the RNA binding protein Hfq are prominent mechanisms of defense against transposition. Recent transcriptomics analyses have identified many new cases of antisense RNAs (asRNA) that potentially could regulate the expression of transposon-encoded genes giving the impression that asRNA regulation of DNA-based transposons is much more frequent than previously thought. Hfq is a highly conserved bacterial protein that plays a central role in posttranscriptional gene regulation and stress response pathways in many bacteria. Three different mechanisms for Hfq directed control of bacterial transposons have been identified to date highlighting the versatility of this protein as a regulator of bacterial transposons. There is also evidence emerging that some DNA-based transposons encode RNAs that could regulate expression of host genes. In the case of IS200, which appears to have lost its ability to transpose, contributing a regulatory RNA to its host could account for the persistence of this mobile element in a wide range of bacterial species. It remains to be seen how prevalent these transposon-encoded RNA regulators are, but given the relatively large amount of intragenic transcription in bacterial genomes, it would not be surprising if new examples are forthcoming. WIREs RNA 2016, 7:382-398. doi: 10.1002/wrna.1341 For further resources related to this article, please visit the WIREs website. PMID- 26846463 TI - Evaluation of a new low sheath-flow interface for CE-MS. AB - The current trend for increasing technical complexity in the field of CE-ESI-MS interfaces has incited for more accessible alternatives. In this work, a simple low sheath-flow ESI interface operating in the submicroliter nanospray regime without nebulizing gas assistance was evaluated. The use of sheath liquid enabled improving the ionization of the analytes, while the absence of nebulizing gas minimized sample dilution and loss of efficiency. After a rapid qualification, the effect of main operational parameters such as sheath liquid composition and flow rate, working distance and ESI potential was studied. Simulation of the mixing processes inside the Taylor cone proved its size to be of utmost importance in band broadening processes. As a proof of concept, the interface was eventually applied to a set of representative basic drugs analyzed by CE-TOF/MS. Limits of detection reached the 25-100 ppb range with suitable robustness and repeatability results. This design has demonstrated good performance while being simple and accessible to the user. PMID- 26846464 TI - Five year survivorship of primary non-modular stemless constrained knee arthroplasty. AB - INTRODUCTION: Recent development of stemless non-modular constrained (NMC) condylar components has offered solutions to end of stem pain, canal invasion, and complicated revision. However, supposed improvement in fixation associated with stems has led to some fears about non-modular (NM) devices and aseptic loosening. The purpose of this study was to evaluate the average five-years survivorship and clinical results of this newer primary NM constrained condylar arthroplasty. METHODS: We retrospectively reviewed 184 primary (TKAs) (140 patients) utilizing a newer NMC condylar implant from 1999 to 2008. Pre-operative range of motion and Knee Society function scores were obtained and compared to that of the patients' most recent follow-up. Statistical analysis included Kaplan Meier survivorship analysis of all knees, with failure defined as the removal of the implant for any reason. RESULTS: Follow-up averaged 5years (range: 2-9). Of the entire cohort, 42 patients are deceased and 14 knees have been revised. Of the 7 patients revised for loosening, 6 were isolated for femoral component loosening (3.3%). There was a significant improvement in both postoperative knee score and function score (p<0.05). The 5-year survival was 97.3%. CONCLUSION: The use of constraint should be judicious and ligament balancing, but we recommend using the least amount of constraint necessary to achieve stability. In addition, because of a significant number of isolated femoral loosenings observed in our cohort of stemless NMC knee prostheses, we recommend the use of a femoral stem with constrained condylar knee prosthesis in patients that have osteopenia and require a constrained knee. PMID- 26846466 TI - Introductory editorial: Effects of maternal physical activity on the fetus. PMID- 26846465 TI - Non-resurfacing techniques in the management of the patella at total knee arthroplasty: A systematic review and meta-analysis. AB - BACKGROUND: Recent meta-analyses support not resurfacing the patella at the time of TKA. Several different modes of intervention are reported for non-resurfacing management of the patella at TKA. METHODS: We have conducted a systematic review and meta-analysis of non-resurfacing interventions in TKA. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) study methodology and reporting system was adopted, utilising the PRISMA checklist and statement. Classes of patella interventions were defined as: 0. No intervention. 1. Osteophyte excision only. 2. Osteophyte excision, denervation, with soft tissue debridement. 3. Osteophyte excision, denervation, soft tissue debridement, and drilling or micro-fracture of eburnated bone. 4. Patellar resurfacing. A meta analysis was conducted upon the pre- and post-operative KSS for each technique. RESULTS: Four hundred and twenty-three studies were identified, 12 studies met the inclusion criteria for the systematic review and eight for the meta-analysis. Two studies compared different non-resurfacing patellar techniques, the other studies used the non-resurfacing cohort as controls for their prospective RCTs comparing patellar resurfacing with non-resurfacing. The meta-analysis revealed no significant difference between the techniques. CONCLUSIONS: We conclude that there is no significant difference in KSS for differing non-resurfacing patellar techniques, but further trials using patellofemoral specific scores may better demonstrate superior efficacy of specific classes of patella intervention, by virtue of greater sensitivity for patellofemoral pain and dysfunction. LEVEL OF EVIDENCE: I. PMID- 26846468 TI - Spatial variation of insecticide resistance in the dengue vector Aedes aegypti presents unique vector control challenges. AB - BACKGROUND: Dengue is a major public health problem in Mexico, where the use of chemical insecticides to control the principal dengue vector, Aedes aegypti, is widespread. Resistance to insecticides has been reported in multiple sites, and the frequency of kdr mutations associated with pyrethroid resistance has increased rapidly in recent years. In the present study, we characterized patterns of insecticide resistance in Ae. aegypti populations in five small towns surrounding the city of Merida, Mexico. METHODS: A cross-sectional, entomological survey was performed between June and August 2013 in 250 houses in each of the five towns. Indoor resting adult mosquitoes were collected in all houses and four ovitraps were placed in each study block. CDC bottle bioassays were conducted using F0-F2 individuals reared from the ovitraps and kdr allele (Ile1016 and Cys1534) frequencies were determined. RESULTS: High, but varying, levels of resistance to chorpyrifos-ethyl was detected in all study towns, complete susceptibility to bendiocarb in all except one town, and variations in resistance to deltamethrin between towns, ranging from 63-88% mortality. Significant associations were detected between deltamethrin resistance and the presence of both kdr alleles. Phenotypic resistance was highly predictive of the presence of both alleles, however, not all mosquitoes containing a mutant allele were phenotypically resistant. An analysis of genotypic differentiation (exact G test) between the five towns based on the adult female Ae. aegypti collected from inside houses showed highly significant differences (p < 0.0001) between genotypes for both loci. When this was further analyzed to look for fine scale differences at the block level within towns, genotypic differentiation was significant for both loci in San Lorenzo (Ile1016, p = 0.018 and Cys1534, p = 0.007) and for Ile1016 in Acanceh (p = 0.013) and Conkal (p = 0.031). CONCLUSIONS: The results from this study suggest that 3 years after switching chemical groups, deltamethrin resistance and a high frequency of kdr alleles persisted in Ae. aegypti populations. The spatial variation that was detected in both resistance phenotypes and genotypes has practical implications, both for vector control operations as well as insecticide resistance management strategies. PMID- 26846469 TI - Dracorhodin perchlorate induces the apoptosis of glioma cells. AB - Dracorhodin perchlorate (Dp), a synthetic analogue of the antimicrobial anthocyanin red pigment, has recently been shown to induce apoptotic cell death in various types of cancer cells. Yet, the inhibitory effect of Dp on human glioma cells remains uninvestigated. Therefore, in the present study, 3-[4,5 dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to detect cell viability and cell cycle progression in glioma U87MG and T98G cells, respectively. Annexin V-FITC/propidium iodide double staining and JC-1 staining were separately applied to determine cellular apoptosis and mitochondrial membrane potential damage in the cells. The expression levels of associated proteins involved in cell cycle progression and apoptosis were measured by western blotting. The activities of caspase-9/-3 were determined by Caspase-Glo-9/3 assay. The results indicated that Dp treatment significantly inhibited cell proliferation in a dose- and time-dependent manner, and blocked cell cycle progression at the G1/S phase in the U87MG and T98G cells via the upregulation of p53 and p21 protein expression, and simultaneous downregulation of Cdc25A, Cdc2 and P-Cdc2 protein expression. Additionally, Dp treatment led to the loss of cellular mitochondrial membrane potential, and the release of cytochrome c, and strongly induced the occurence of apoptosis. Increased expression levels of Bim and Bax protein and the downregulated expression of Bcl-2 protein were observed. Caspase-9/-3 were activated and their activities were elevated after Dp treatment. These findings indicate that Dp inhibits cell proliferation, induces cell cycle arrest and apoptosis in glioma cells, and is a possible candidate for glioma treatment. PMID- 26846470 TI - Plasma exchange for acute on chronic liver failure: is there a light at the end of the tunnel? PMID- 26846471 TI - A randomised controlled trial of meloxicam, a Cox-2 inhibitor, to prevent hepatocellular carcinoma recurrence after initial curative treatment. AB - BACKGROUND: Because the recurrence rate of hepatocellular carcinoma (HCC) is high, even after curative treatments such as hepatic resection and microwave ablation, chemopreventive agents that can effectively suppress HCC recurrence are required. Cyclooxygenase-2 (Cox-2) was recently found to be overexpressed in HCC. Therefore, Cox-2 inhibitors may offer a chemopreventive therapy for HCC. This randomised controlled trial (RCT) investigated the potential for meloxicam, a clinically used Cox-2 inhibitor, to prevent HCC recurrence after initial curative treatment. METHODS: A total of 232 consecutive patients underwent hepatic resection and/or microwave ablation as initial therapy for HCC at our institute between July 2008 and April 2011. Eight patients were excluded because of poor renal function, history of non-steroidal anti-inflammatory drug-related ulceration, or multiple cancers. The remaining 224 patients were randomised to a control group (n = 113) or a meloxicam group (n = 111). To patients in the meloxicam group, meloxicam was administered at 15 mg daily (5 mg three times a day) as long as possible. The overall survival (OS) and disease-free survival (DFS) rates were determined. RESULTS: The 1-, 3-, and 5-year OS rates of the meloxicam group were 95.4, 82.4, and 70.1 %, respectively. Those of the control group were 98.2, 85.1, and 71.5 %, respectively (p = 0.9549). The corresponding DFS rates of the meloxicam group were 89.2, 53.9, and 44.0 % and those of control group were 86.5, 57.0, and 43.4 %, respectively (p = 0.6722). In the OS and DFS of subsets including patients with hepatitis B or C virus infection, we could not find significant differences between the meloxicam and control groups. However, in the subgroup of analysis of patients without viral hepatitis (NBNC-HCC), significant differences were observed in the DFS between the meloxicam group (1 year DFS, 92.3 %; 3-year DFS, 75.8 %; 5-year DFS, 70.4 %) and control group (1 year DFS, 83.3 %; 3-year DFS, 48.1 %; 5-year DFS, not obtained) (p = 0.0211). CONCLUSION: Administration of the Cox-2 inhibitor meloxicam may have a possibility to suppress HCC recurrence after initial curative treatments in patients with NBNC-HCC. PMID- 26846472 TI - Life cycle of Nosomma monstrosum (Acari: Ixodidae) under laboratory conditions. AB - Nosomma monstrosum (Nuttall & Warburton) is a hard tick infesting mainly buffalo and cattle in Sri Lanka. Biological data on the life cycle pattern of N. monstrosum were collected using experimental infestation on New Zealand white rabbits under laboratory conditions. The three-host life cycle was completed within 64-102 days. Eggs hatched after 20-29 days of incubation and the larvae hatched out started feeding which lasted for 2-4 days. After a moulting period of 8-11 days nymphs emerge and they actively fed for 2-4 days. Subsequently the nymphs took 15-18 days for moulting before emerging as adults. Freshly moulted females fed for 7-8 days and remained latent for 4-5 days before starting the oviposition. Females laid 3864-12,520 eggs for 11-17 days. The male: female sex ratio was 8:3 in the adults which were moulted under laboratory conditions. Strong positive correlations were found in female weight with number of eggs laid and REI. Females raised from the first generation of eggs had higher oviposition periods, higher REI, laid ten times more eggs, and lower pre-oviposition periods compared to those collected from the wild. When a suitable host is given, N. monstrosum could successfully complete its three-host life cycle under laboratory conditions. PMID- 26846473 TI - Oribatid mite species numbers increase, densities decline and parthenogenetic species suffer during bog degradation. AB - This study compared the oribatid mites in two natural and four industrially exploited bogs. One natural bog (Zakret, Z) was located in northeastern Poland and the other one (Toporowy Staw Nizni, TSN), in southern Poland. The four exploited bogs were also located in southern Poland and can be ranked from least to most degraded as follows: Lysa Puscizna (LP), Baligowka (B), Puscizna Mala (PM) and Kaczmarka (K). In the natural bogs, the water pH was higher than in the degraded ones, but other parameters were lower (conductivity, colour value, oxygen demand, and concentration of chlorides). In the natural bogs, the Oribatida were highly abundant (average density was 169,100 ind./m(2)), but with low species diversity and one dominating species. In bog Z the most abundant was Limnozetes foveolatus that had dominance of 75 % and in bog TSN, located at higher altitude, Trimalaconothrus maior dominated (73 %). In two degraded bogs that had still good water conditions (LP and B) the oribatid communities resembled those from the natural bogs; in LP the most abundant species was Hydrozetes lacustris and in bog B, L. foveolatus. In contrast, in two more degraded bogs (PM and K) the abundance of mites was lower (average density was 17,850 ind./m(2)), species diversity of the Oribatida was higher, and no species achieved a high dominance like in the natural bogs. Additionally, in more degraded bogs the abundance of parthenogenetic species was lower than in the natural bogs. PMID- 26846474 TI - On the mechanism of gating defects caused by the R117H mutation in cystic fibrosis transmembrane conductance regulator. AB - KEY POINTS: Two functional abnormalities of cystic fibrosis transmembrane conductance regulator (CFTR), a 25% reduction of the single-channel conductance (g) and a ~13-fold lower open probability (Po ), were found with the R117H mutation that is associated with mild forms of cystic fibrosis. Characterizations of the gating defects of R117H-CFTR led to the conclusion that the mutation decreases Po by perturbing the gating conformational changes in CFTR's transmembrane domains (TMDs) without altering the function of the nucleotide binding domains (NBDs). Nonetheless, gating of the R117H-CFTR can be improved by a variety of pharmacological reagents supposedly acting on NBDs such as ATP analogues, or TMDs (e.g. VX-770 or nitrate). These reagents potentiate synergistically R117H-CFTR gating to a level that allows accurate assessments of its gating deficits. Our studies not only elucidate the mechanism underpinning gating dysfunction of R117H-CFTR, but also provide a mechanistic understanding of how VX-770 ameliorates the gating defects in the R117H mutant. ABSTRACT: Cystic fibrosis (CF) is caused by loss-of-function mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene encoding a phosphorylation activated, but ATP-gated chloride channel. In the current study, we investigated the mechanism responsible for the gating defects manifested in R117H-CFTR, an arginine-to-histidine substitution at position 117 of CFTR that is associated with mild forms of CF. We confirmed previous findings of a 25% decrease of the single-channel conductance (g) in R117H-CFTR, but found a ~13-fold lower open probability (Po ). This dramatic gating deficit is not due to dysfunctional nucleotide binding domains (NBDs) as the mutation does not alter the apparent affinity for ATP, and the mutant channels respond to ATP analogues in a similar manner as wild-type CFTR. Furthermore, once ATP hydrolysis is abolished, the R117H mutant can be trapped in a prolonged 'burst opening' conformation that is proposed to be equipped with a stable NBD dimer. On the other hand, our results support the conclusion that the R117H mutation decreases Po by perturbing the gating conformational changes in CFTR's transmembrane domains as even when NBDs are kept at a dimerized configuration, Po is reduced by ~10-fold. Moreover, our data demonstrate that a synergistic improvement of R117H-CFTR function can be accomplished with a combined regiment of VX-770 (Ivacaftor), nitrate ion (NO3 (-) ) and N(6) -(2-phenylethyl)-2'-deoxy-ATP (d-PATP), which almost completely rectifies the gating defect of R117H-CFTR. Clinical implications of our results are discussed. PMID- 26846476 TI - Systematic Review and Meta-Analysis of Peer-Led Self-Management Programs for Increasing Physical Activity. AB - PURPOSE: Approximately 85 % of Canadians are not physically active enough to achieve health benefits. Peer-led self-management programs are becoming an increasingly popular strategy for modifying health behaviors, including physical activity. The purpose of this study was to systematically review and meta-analyze the effect of peer-led self-management interventions on physical activity. METHODS: PubMed, MEDLINE, PsycINFO, EMBASE, CINAHL, and Cochrane Database of Systematic Reviews databases were systematically searched to identify all relevant randomized controlled trials that evaluated the effect of peer-led self management on physical activity. The studies were described and effect size data were included in meta-analyses. Subgroup analyses were performed according to type of physical activity outcome (i.e., duration, frequency, other). RESULTS: Twenty-one studies were included in the review and 14 reported statistically significant improvements in physical activity. A meta-analysis of 17 studies showed a statistically significant moderate pooled effect (standardized mean difference (SMD) = 0.4, p < 0.001) of peer-led self-management programs on physical activity immediately post-intervention. The intervention had a large statistically significant effect based on the four studies that included follow up measures (SMD = 1.5, p = 0.03). Meta-analysis of nine studies that used similar outcomes (i.e., minutes of physical activity) revealed a statistically significant small effect (SMD = 0.2, p < 0.001). CONCLUSION: Peer-led self management programs appear to be effective at increasing weekly duration of physical activity in various populations, but the effect size is small. Training peers to encourage increased physical activity may provide an effective method for reaching various clinical and non-clinical populations. More research is needed using validated and consistent physical activity outcomes. PMID- 26846477 TI - We Can Work it Out: The Importance of Rupture and Repair Processes in Infancy and Adult Life for Flourishing. AB - This paper argues that insights into infant emotional development, particularly the capacity to engage with rupture and repair, can be applied to the understanding and promotion of flourishing in later life, individually and socially. Starting with the Queen's visit to the Republic of Ireland as an example of successful social repair after rupture that enables flourishing, the paper goes on to outline some relevant psychological theory that undergirds this. It then considers some of the practical relevance and problems that apply to rupture and repair in the contemporary world, particularly the world of health care, Amidst the inevitable messiness of life, flourishing and growth can only be achieved with the kind of flexibility implied by creating repair in the face of rupture. PMID- 26846475 TI - A Validation and Generality Study of the Committed Action Questionnaire in a Swedish Sample with Chronic Pain. AB - PURPOSE: Psychological flexibility is the theoretical model that underpins Acceptance Commitment Therapy (ACT). There is a growing body of evidence indicating that ACT is an effective treatment for chronic pain but one component of the model, committed action, has not been sufficiently researched. The purpose of this study is to validate Swedish-language versions of the full length Committed Action Questionnaire (CAQ; CAQ-18) and the shortened CAQ (CAQ-8), to examine the generality of previous results related to committed action and to further demonstrate the relevance of this construct to the functioning of patients with chronic pain. METHOD: The study includes preliminary analyses of the reliability and validity of the CAQ. Participants were 462 consecutive referrals to the Pain Rehabilitation Unit at Skane University Hospital. RESULTS: The Swedish-language versions of the CAQ (CAQ-18 and CAQ-8) demonstrated high levels of internal consistency and satisfactory relationships with various indices of patient functioning and theoretically related concepts. Confirmatory factor analyses showed that the Swedish versions of the CAQ yielded similar two factor models as found in the original validation studies. Hierarchical regression analyses identified the measures as significant contributors to explained variance in patient functioning. CONCLUSION: The development, translation and further validation of the CAQ is an important step forward in evaluating the utility of the psychological flexibility model to the treatment of chronic pain. The CAQ can both assist researchers interested in mediators of chronic pain treatment and further enable research on change processes within the psychological flexibility model. PMID- 26846478 TI - A Unique Tryptophan C-Prenyltransferase from the Kawaguchipeptin Biosynthetic Pathway. AB - Cyanobactins are a rapidly growing family of linear and cyclic peptides produced by cyanobacteria. Kawaguchipeptins A and B, two macrocyclic undecapeptides reported earlier from Microcystis aeruginosa NIES-88, are shown to be products of the cyanobactin biosynthetic pathway. The 9 kb kawaguchipeptin (kgp) gene cluster was identified in a 5.26 Mb draft genome of Microcystis aeruginosa NIES-88. We verified that this gene cluster is responsible for the production of the kawaguchipeptins through heterologous expression of the kgp gene cluster in Escherichia coli. The KgpF prenyltransferase was overexpressed and was shown to prenylate C-3 of Trp residues in both linear and cyclic peptides in vitro. Our findings serve to further enhance the structural diversity of cyanobactins to include tryptophan-prenylated cyclic peptides. PMID- 26846479 TI - Lentiviral-mediated overexpression of long non-coding RNA GAS5 reduces invasion by mediating MMP2 expression and activity in human melanoma cells. AB - The present study evaluated the effects of long non-coding RNA GAS5 on the migration and invasion of melanoma cells. Using the SK-Mel-110 melanoma cell line, we stably expressed GAS5, visualized the distribution of GAS5 by RNA fluorescence in situ hybridization (FISH) and examined changes in cell migration and invasion with Transwell assays. In GAS5 overexpressed SK-Mel-110 cells, migrated and invaded cells decreased by 65.3 and 55.6%, respectively. Moreover, the MMP2 protein level, and its activity was downregulated by 67.9 and 15.8%, respectively. Overexpressing lncRNA GAS5 inhibited the migration and invasion ability of melanoma SK-Mel-110 cells, partially by decreasing the MMP2 expression and its activity. This study is the first to reveal a potential relationship between lncRNA GAS5 and the migration and invasion of melanoma. PMID- 26846481 TI - Which Diagnostic Criteria are Most Useful in Discriminating Between Social Gamblers and Individuals with Gambling Problems? An Examination of DSM-IV and DSM 5 Criteria. AB - The current study sought to identify which diagnostic criteria for gambling disorder have the greatest ability to differentiate between social and problem gamblers. This study was conducted on a sample of male and female college student athletes across the U.S. (n = 8674). Classification and regression tree analysis represents an appropriate technique when addressing the question of an item's diagnostic value, as it sequentially selects variables to isolate sets of observations with similar outcomes. The current results suggest that the item related to preoccupation ("Have there been periods in the past year where you spent a lot of time thinking about gambling?") was the DSM-5 item best able to differentiate between male and female social and problem gamblers in this sample. When considering only the nine criteria retained in the DSM-5, three criteria were identified as key for distinguishing between social and disordered gamblers among men, and one criterion was identified for distinguishing between groups of women. In addition, these results do not support the notion that the illegal acts criterion has a particularly low base rate and found that it can be an important indicator of disordered gambling in a college-aged sample. PMID- 26846480 TI - Positive selection in the SLC11A1 gene in the family Equidae. AB - Immunity-related genes are a suitable model for studying effects of selection at the genomic level. Some of them are highly conserved due to functional constraints and purifying selection, while others are variable and change quickly to cope with the variation of pathogens. The SLC11A1 gene encodes a transporter protein mediating antimicrobial activity of macrophages. Little is known about the patterns of selection shaping this gene during evolution. Although it is a typical evolutionarily conserved gene, functionally important polymorphisms associated with various diseases were identified in humans and other species. We analyzed the genomic organization, genetic variation, and evolution of the SLC11A1 gene in the family Equidae to identify patterns of selection within this important gene. Nucleotide SLC11A1 sequences were shown to be highly conserved in ten equid species, with more than 97 % sequence identity across the family. Single nucleotide polymorphisms (SNPs) were found in the coding and noncoding regions of the gene. Seven codon sites were identified to be under strong purifying selection. Codons located in three regions, including the glycosylated extracellular loop, were shown to be under diversifying selection. A 3-bp indel resulting in a deletion of the amino acid 321 in the predicted protein was observed in all horses, while it has been maintained in all other equid species. This codon comprised in an N-glycosylation site was found to be under positive selection. Interspecific variation in the presence of predicted N-glycosylation sites was observed. PMID- 26846483 TI - Environmental Health: Children's Health, a Clinician's Dilemma. AB - Few pediatricians receive training in environmental health, yet accumulating research shows that a disproportionate burden of exposure from environmental toxicants (man-made contaminants) is borne by children, adolescents, and the developing fetus. This is explained in part because of children's vulnerability to environmental-toxicants based on socioeconomic status, body surface area, metabolism, and potential transfers via placenta and breast milk. Public concern about toxicants affecting children in air, land, water, food, and beverages places pediatricians in the challenging position of being expected to knowledgably answer questions about environmental exposures while lacking sufficient training in the field. Surveys show pediatricians have high interest in environmental topics, yet feel a low sense of self-efficacy regarding patient education and lack evidence-based treatment guidelines and other effective educational tools. The goal of this article is to provide an overview of selected toxicants relevant to pediatric health, review practical suggestions to reduce or eliminate children's exposures, and introduce resources for taking an environmental health history to better prepare pediatricians and other clinicians caring for children to decrease harmful exposures in infants, children, and adolescents. PMID- 26846482 TI - Reward Preferences of Pathological Gamblers Under Conditions of Uncertainty: An Experimental Study. AB - Among many personality traits, impulsivity represents one of the most important traits associated with pathological gambling. Empirical research has highlighted the multidimensional nature of impulsivity, which includes different heterogeneous traits and behavioral tendencies. The present study experimentally examined reward preferences of pathological gamblers under conditions of uncertainty using the Balloon Analogue Risk Task (BART). Furthermore it also examined the relationship between impulsivity, time perspective, inability to tolerate delay in gratification, and risk-taking. The present study is the first to simultaneously examine all these variables simultaneously in a sample of pathological gamblers (n = 54) and healthy controls (n = 54) from Italy. All participants participated in the BART and were also administered Italian versions of the South Oaks Gambling Screen, the Barratt Impulsiveness Scale, the Consideration of Future Consequences, and the Monetary Choice Questionnaire. Analyses revealed that compared to HCs, PGs were more risk prone on the BART, and reported elevated levels of impulsivity, steeper discounting rates and a shorter time perspective. All the measures correlated with the gambling severity and strong correlations between the BIS, CFC-14 and BART were observed. Logistic regression analysis demonstrated that impulsivity and risk-taking were strong predictors of pathological gambling. PMID- 26846484 TI - Effects of the tumor suppressor PTEN on the pathogenesis of idiopathic pulmonary fibrosis in Chinese patients. AB - Idiopathic pulmonary fibrosis (IPF) is characterized by progressive interstitial fibrosis, and is associated with a fatal outcome. The critical pathological mechanisms underlying IPF are largely unknown; however, accumulating evidence has indicated similarities between IPF and cancer. Therefore, the present study examined the expression levels of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in Chinese patients with IPF, using an enzyme-linked immunosorbent assay. To determine the effects of PTEN on the development of pulmonary fibrosis, PTEN was overexpressed in transforming growth factor (TGF)-beta1-treated human embryonic lung fibroblasts (HFL-I cells). The serum levels of PTEN were significantly lower in 42 patients with IPF, as compared with in the healthy controls. In addition, PTEN overexpression enhanced apoptosis, and suppressed basal levels of proliferation and migration in fibroblasts. Notably, PTEN was able to specifically inhibit TGF-beta1-induced proliferation and migration of the cells. Overexpression of PTEN also suppressed phosphorylation of Akt and Smad3, and decreased the expression levels of numerous proteins with critical roles in TGF-beta1-induced fibrosis, including alpha smooth muscle actin, matrix metalloproteinase (MMP)-2 and MMP-9. These results indicated that PTEN may inhibit TGF-beta1-mediated myofibroblast differentiation of fibroblasts by attenuating signaling via the phosphatidylinositol 3-kinase/Akt and TGF-beta/Smad3 pathways. PMID- 26846485 TI - Pharmacokinetics of Saquinavir Mesylate from Oral Self-Emulsifying Lipid-Based Delivery Systems. AB - BACKGROUND AND OBJECTIVES: Although lipid-based drug delivery systems have gained much importance in recent years due to their ability to improve the solubility and bioavailability of poorly soluble drugs, compartmental pharmacokinetic analyses have not been extensively explored. The oral pharmacokinetics of commercial liquid formulation and a developed semisolid system containing saquinavir mesylate (SQVM) were compared in Beagle dogs. A compartmental analysis after intravenous bolus administration of this drug (1 mg/kg) was also performed. METHOD: Pharmacokinetic profiles were analyzed using both non-compartmental and compartmental approaches. Plasma concentration of the drug was determined by high performance liquid chromatography/tandem mass spectrometry (LC/MS/MS). RESULTS: The disposition curve of SQVM given intravenously was better described by a three compartment model. In contrast, plasma profiles obtained following the oral administration were fitted to a two-compartment model with lag time due to the fact that the distribution phase was masked by the absorption phase in these formulations. CONCLUSION: The proposed semisolid lipid system was found to be a promising formulation for commercial purposes given the similarity of SQVM absorption rate to that from the commercial liquid formulation. PMID- 26846487 TI - Sex, lies and gender. PMID- 26846488 TI - Why parents should not be told the sex of their fetus. AB - A new technique called non-invasive prenatal testing (NIPT) has been developed, which can detect a range of genetic and chromosomal diseases, as well as fetal sex earlier, more easily and more reliably. NIPT, therefore, potentially expands the market for sex determination and sex selective abortion. This paper argues that both practices should be prevented by not including fetal sex in prenatal test reports. This is because there is a discrepancy between what parents are concerned with (gender) and what the prenatal test can provide (sex). The paper first presents arguments, which indicate a difference between sex and gender before presenting parental motivations for sex selection and sex determination to show that parents are not concerned with their child's sex chromosomes, or even their genitalia, but the gender role that their child will espouse. That, however, is not something that a prenatal test can provide. We are thus left with a situation in which what parents are told, and what they think they are being told, are two different things. In other words, as the conflation of sex with gender is implicit in the disclosure of fetal sex, it may be more accurate to refer to it as misinformation. This misinformation promotes sexism via gender essentialism, which is neither in the interests of the future child nor society. PMID- 26846489 TI - Yes. Yes but. PMID- 26846490 TI - A bar too high: why we should not bar parents from knowing the sex of their fetus. PMID- 26846491 TI - Synthesis and crystal structures of the potential tyrosinase inhibitors N-(4 acetylphenyl)-2-chloroacetamide and 2-(4-acetylanilino)-2-oxoethyl cinnamate. AB - Substituted benzoic acid and cinnamic acid esters are of interest as tyrosinase inhibitors and the development of such inhibitors may help in diminishing many dermatological disorders. The tyrosinase enzyme has also been linked to Parkinson's disease. In view of hydroxylated compounds having ester and amide functionalities to potentially inhibit tyrosinase, we herein report the synthesis and crystal structures of two amide-based derivatives, namely N-(4-acetylphenyl) 2-chloroacetamide, C10H10ClNO2, (I), and 2-(4-acetylanilino)-2-oxoethyl cinnamate, C19H17NO4, (II). In compound (I), the acetylphenyl ring and the N (C=O)-C unit of the acetamide group are almost coplanar, with a dihedral angle of 7.39 (18) degrees . Instead of esterification, a cheaper and more efficient synthetic method has been developed for the preparation of compound (II). The molecular geometry of compound (II) is a V-shape. The acetamide and cinnamate groups are almost planar, with mean deviations of 0.088 and 0.046 A, respectively; the dihedral angle between these groups is 77.39 (7) degrees . The carbonyl O atoms are positioned syn and anti to the amide carbonyl O atom. In the crystals of (I) and (II), N-H...O, C-H...O and C-H...pi interactions link the molecules into a three-dimensional network. PMID- 26846492 TI - Assembly of Zn(II) and Cd(II) coordination polymers based on a flexible multicarboxylate ligand and nitrogen-containing auxiliary ligands through a mixed ligand synthetic strategy: syntheses, structures and fluorescence properties. AB - The structures of coordination polymers are strongly influenced by the organic ligands and metal ions used for their construction, so it is important to choose suitable ligands and metal ions and appropriate synthetic processes. Two novel d(10) coordination polymers, namely poly[[diaquabis(2,2'-bipyridine)[MU4-4,4' (1,4-phenylenedioxy)bis(benzene-1,2-dicarboxylato)]dizinc(II)] dihydrate], {[Zn2(C22H10O10)(C10H8N2)2(H2O)2].2H2O}n, (1), and poly[[diaquabis(1,10 phenanthroline)[MU4-4,4'-(1,4-phenylenedioxy)bis(benzene-1,2 dicarboxylato)]dicadmium(II)] dimethylformamide disolvate], {[Cd2(C22H10O10)(C12H8N2)2(H2O)2].2C3H7NO}n, (2), have been synthesized from 4,4' (1,4-phenylenedioxy)bis(benzene-1,2-dicarboxylic acid) (H4L) and two different N containing auxiliary ligands through a mixed-ligand synthetic strategy under a solvothermal environment. The structures were characterized by single-crystal X ray diffraction, powder X-ray diffraction, elemental analysis and IR spectroscopy. Compounds (1) and (2) both present one-dimensional chain structures and two-dimensional supramolecular layer structures constructed by weak hydrogen bonds. It is interesting to note that the carboxylate ligands reveal stable trans configurations in both compounds. The fluorescence properties of (1) and (2) in the solid state were also investigated. PMID- 26846493 TI - Cyclic heterotetrameric and low-dimensional hydrogen-bonded polymeric structures in the morpholinium salts of ring-substituted benzoic acid analogues. AB - The morpholinium (tetrahydro-2H-1,4-oxazin-4-ium) cation has been used as a counter-ion in both inorganic and organic salt formation and particularly in metal complex stabilization. To examine the influence of interactive substituent groups in the aromatic rings of benzoic acids upon secondary structure generation, the anhydrous salts of morpholine with salicylic acid, C4H10NO(+).C7H5O3(-), (I), 3,5-dinitrosalicylic acid, C4H10NO(+).C7H3N2O7(-), (II), 3,5-dinitrobenzoic acid, C4H10NO(+).C7H3N2O6(-), (III), and 4 nitroanthranilic acid, C4H10NO(+).C7H5N2O4(-), (IV), have been prepared and their hydrogen-bonded crystal structures are described. In the crystal structures of (I), (III) and (IV), the cations and anions are linked by moderately strong N H...Ocarboxyl hydrogen bonds, but the secondary structure propagation differs among the three, viz. one-dimensional chains extending along [010] in (I), a discrete cyclic heterotetramer in (III), and in (IV), a heterotetramer with amine N-H...O hydrogen-bond extensions along b, giving a two-layered ribbon structure. With the heterotetramers in both (III) and (IV), the ion pairs are linked though inversion-related N-H...Ocarboxylate hydrogen bonds, giving cyclic R4(4)(12) motifs. With (II), in which the anion is a phenolate rather than a carboxylate, the stronger assocation is through a symmetric lateral three-centre cyclic R1(2)(6) N-H...(O,O') hydrogen-bonding linkage involving the phenolate and nitro O-atom acceptors of the anion, with extension through a weaker O-H...Ocarboxyl hydrogen bond. This results in a one-dimensional chain structure extending along [100]. In the structures of two of the salts [i.e. (II) and (IV)], there are also pi-pi ring interactions, with ring-centroid separations of 3.5516 (9) and 3.7700 (9) A in (II), and 3.7340 (9) A in (IV). PMID- 26846494 TI - Reaction-path calculations and crystal structures of 1,1'-(ethylene-1,2 diyl)dipyridinium dichloride dihydrate and 1,1'-(ethylene-1,2-diyl)dipyridinium dibromide. AB - The design of new organic-inorganic hybrid ionic materials is of interest for various applications, particularly in the areas of crystal engineering, supramolecular chemistry and materials science. The monohalogenated intermediates 1-(2-chloroethyl)pyridinium chloride, C5H5NCH2CH2Cl(+).Cl(-), (I'), and 1-(2 bromoethyl)pyridinium bromide, C5H5NCH2CH2Br(+).Br(-), (II'), and the ionic disubstituted products 1,1'-(ethylene-1,2-diyl)dipyridinium dichloride dihydrate, C12H14N2(2+).2Cl(-).2H2O, (I), and 1,1'-(ethylene-1,2-diyl)dipyridinium dibromide, C12H14N2(2+).2Br(-), (II), have been isolated as powders from the reactions of pyridine with the appropriate 1,2-dihaloethanes. The monohalogenated intermediates (I') and (II') were characterized by multinuclear NMR spectroscopy, while (I) and (II) were structurally characterized using powder X-ray diffraction. Both (I) and (II) crystallize with half the empirical formula in the asymmetric unit in the triclinic space group P-1. The organic 1,1'-(ethylene-1,2 diyl)dipyridinium dications, which display approximate C2h symmetry in both structures, are situated on inversion centres. The components in (I) are linked via intermolecular O-H...Cl, C-H...Cl and C-H...O hydrogen bonds into a three dimensional framework, while for (II), they are connected via weak intermolecular C-H...Br hydrogen bonds into one-dimensional chains in the [110] direction. The nucleophilic substitution reactions of 1,2-dichloroethane and 1,2-dibromoethane with pyridine have been investigated by ab initio quantum chemical calculations using the 6-31G** basis. In both cases, the reactions occur in two exothermic stages involving consecutive SN2 nucleophilic substitutions. The isolation of the monosubstituted intermediate in each case is strong evidence that the second step is not fast relative to the first. PMID- 26846495 TI - Syntheses and structures of discrete copper(II) and cadmium(II) supramolecular complexes based on 1,4-diacylthiosemicarbazone ligands. AB - Thiosemicarbazides and their metal complexes have attracted considerable interest because of their biological activities and their flexibility, which allows the ligands to bend and rotate freely to accommodate the coordination geometries of various metal centres. Discrete copper(II) and cadmium(II) complexes have been prepared by crystallization of N-[2-(2 hydroxybenzoyl)hydrazinecarbonothioyl]propanamide (H3L) with Cu(CH3COO)2 or Cd(NO3)2 in a dimethylformamide/methanol mixed-solvent system at room temperature, affording the complexes di-MU-acetato-bis{MU4-1-[(2 oxidophenyl)carbonyl]-2-(propanamidomethanethioyl)hydrazine-1,2 diido}tetracopper(II) dimethylformamide disolvate, [Cu4(C11H10N3O3S)2(C2H3O2)2].2C3H7NO, (I), and bis{MU2-[(2 hydroxyphenyl)formamido](propanamidomethanethioyl)azanido}bis[(4,4' bipyridine)nitratocadmium(II)] dihydrate, [Cd2(C11H12N3O3S)2(NO3)2(C10H8N2)2].2H2O, (II). Complex (I) consists of four Cu(II) cations, two MU4-bridging trianionic ligands and two MU2-bridging acetate ligands, while complex (II) is composed of two Cd(II) cations, two MU2-bridging monoanionic ligands, two nitrate ligands and two 4,4'-bipyridine ligands. These discrete complexes are connected by hydrogen bonds and van der Waals interactions to form a three-dimensional supramolecular architecture. Compared with (I), the phenolic hydroxy group and hydrazide N atom of the thiosemicarbazide ligand of (II) are not involved in coordination and lead to a binuclear Cd(II) complex. This different coordination mode may be attributed to the larger ionic radius of the Cd(II) ion compared with the Cu(II) ion. PMID- 26846496 TI - Nobiletin: a citrus flavonoid displaying potent physiological activity. AB - Nobiletin [systematic name: 2-(3,4-dimethoxyphenyl)-5,6,7,8-tetramethoxy-4H chromen-4-one; C21H22O8] is a flavonoid found in citrus peels, and has been reported to show a wide range of physiological properties, including anti inflammatory, anticancer and antidementia activities. We have solved the crystal structure of nobiletin, which revealed that the chromene and arene rings of its flavone moiety, as well as the two methoxy groups bound to its arene ring, were coplanar. In contrast, the C atoms of the four methoxy groups bound to the chromene ring are out of the plane, making the molecule conformationally chiral. A comparison of the crystal structures of nobiletin revealed that it could adopt a variety of different conformations through rotation of the covalent bond between the chromene and arene rings, and the orientations of methoxy groups bound to the chromene ring. PMID- 26846497 TI - A threefold interpenetrated two-dimensional zinc(II) supramolecular architecture based on 3-nitrobenzoic acid and 4,4'-bipyridine. AB - With regard to crystal engineering, building block or modular assembly methodologies have shown great success in the design and construction of metal organic coordination polymers. The critical factor for the construction of coordination polymers is the rational choice of the organic building blocks and the metal centre. The reaction of Zn(OAc)2.2H2O (OAc is acetate) with 3 nitrobenzoic acid (HNBA) and 4,4'-bipyridine (4,4'-bipy) under hydrothermal conditions produced a two-dimensional zinc(II) supramolecular architecture, catena-poly[[bis(3-nitrobenzoato-kappa(2)O,O')zinc(II)]-MU-4,4'-bipyridine kappa(2)N:N'], [Zn(C7H4NO4)2(C10H8N2)]n or [Zn(NBA)2(4,4'-bipy)]n, which was characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis and single-crystal X-ray diffraction analysis. The Zn(II) ions are connected by the 4,4'-bipy ligands to form a one-dimensional zigzag chain and the chains are decorated with anionic NBA ligands which interact further through aromatic pi-pi stacking interactions, expanding the structure into a threefold interpenetrated two-dimensional supramolecular architecture. The solid-state fluorescence analysis indicates a slight blue shift compared with pure 4,4'-bipyridine and HNBA. PMID- 26846498 TI - Two-dimensional Zn(II) and one-dimensional Co(II) coordination polymers based on benzene-1,4-dicarboxylate and pyridine ligands. AB - Coordination polymers constructed from metal ions and organic ligands have attracted considerable attention owing to their diverse structural topologies and potential applications. Ligands containing carboxylate groups are among the most extensively studied because of their versatile coordination modes. Reactions of benzene-1,4-dicarboxylic acid (H2BDC) and pyridine (py) with Zn(II) or Co(II) yielded two new coordination polymers, namely, poly[(MU4-benzene-1,4 dicarboxylato-kappa(4)O:O':O'':O''')(pyridine-kappaN)zinc(II)], [Zn(C8H4O2)(C5H5N)]n, (I), and catena-poly[aqua(MU3-benzene-1,4-dicarboxylato kappa(3)O:O':O'')bis(pyridine-kappaN)cobalt(II)], [Co(C8H4O2)(C5H5N)2(H2O)]n, (II). In compound (I), the Zn(II) cation is five-coordinated by four carboxylate O atoms from four BDC(2-) ligands and one pyridine N atom in a distorted square pyramidal coordination geometry. Four carboxylate groups bridge two Zn(II) ions to form centrosymmetric paddle-wheel-like Zn2(MU2-COO)4 units, which are linked by the benzene rings of the BDC(2-) ligands to generate a two-dimensional layered structure. The two-dimensional layer is extended into a three-dimensional supramolecular structure with the help of pi-pi stacking interactions between the aromatic rings. Compound (II) has a one-dimensional double-chain structure based on Co2(MU2-COO)2 units. The Co(II) cations are bridged by BDC(2-) ligands and are octahedrally coordinated by three carboxylate O atoms from three BDC(2-) ligands, one water O atom and two pyridine N atoms. Interchain O-H...O hydrogen-bonding interactions link these chains to form a three-dimensional supramolecular architecture. PMID- 26846499 TI - CB-TE2A(+).Cl(-).3H2O: a short intermolecular hydrogen bond between zwitterionic bicyclo[6.6.2]tetraamine macrocycles. AB - 1,4,8,11-Tetraazabicyclo[6.6.2]hexadecane-4,11-diacetic acid (CB-TE2A) is of much interest in nuclear medicine for its ability to form copper complexes that are kinetically inert, which is beneficial in vivo to minimize the loss of radioactive copper. The structural chemistry of the hydrated HCl salt of CB-TE2A, namely 11-carboxymethyl-1,8-tetraaza-4,11-diazoniabicyclo[6.6.2]hexadecane-4 acetate chloride trihydrate, C16H31N4O4(+).Cl(-).3H2O, is described. The compound crystallized as a positively charged zwitterion with a chloride counter-ion. Two of the amine groups in the macrocyclic ring are protonated. Formally, a single negative charge is shared between two of the carboxylic acid groups, while one chloride ion balances the charge. Two intramolecular hydrogen bonds are observed between adjacent pairs of N atoms of the macrocycle. Two intramolecular hydrogen bonds are also observed between the protonated amine groups and the pendant carboxylate groups. A short intermolecular hydrogen bond is observed between two partially negatively charged O atoms on adjacent macrocycles. The result is a one dimensional polymeric zigzag chain that propagates parallel to the crystallographic a direction. A second intermolecular interaction is a hydrogen bonding network in the crystallographic b direction. The carbonyl group of one macrocycle is connected through the three water molecules of hydration to the carbonyl group of another macrocycle. PMID- 26846500 TI - Bis(triethanolamine)bis(MU2-trimesato)dicobalt(II): a Co(II) dimer with an unreported two-dimensional supramolecular topology formed from triethanolamine and trimesic acid ligands. AB - Supramolecular networks are an important subset in the field of coordination polymer (CP) frameworks and are widely encountered in crystal engineering research. The search for novel topologies continues to be a significant goal in CP chemistry. The dimeric compound bis(MU-5-carboxybenzene-1,3-dicarboxylato kappa(2)O(1):O(3))bis[(triethanolamine-kappa(4)N,O,O',O'')cobalt(II)], [Co2(C9H4O6)2(C6H15NO3)2], formed from the coligands 5-carboxybenzene-1,3 dicarboxylate (tmaH(2-)) and triethanolamine (teaH3), namely [Co(MU2 tmaH)(teaH3)]2, was synthesized and characterized by single-crystal and powder X ray diffraction analyses, IR spectroscopy, thermogravimetric analysis (TGA) and magnetic measurements. The crystal structure features a zero-dimensional molecular structure consisting of centrosymmetric macrocyclic dinuclear complexes. Four classical hydrogen bonds between carboxylate groups and hydroxyethyl arms stabilize and extend the molecules into a two-dimensional supramolecular network. The topological analysis indicates that an unreported (3,5)-binodal supramolecular topology with a short Schlafli symbol of (4.5.6)(4.5(5).6(3).7) can be achieved by means of intermolecular hydrogen bonds. The crystal structure accounts for the potential to obtain unique topological types from two excellent hydrogen-bonding candidates, i.e. tmaH3 and teaH3. A variable-temperature magnetic study shows the existence of antiferromagnetic behaviour in the complex. PMID- 26846501 TI - Synthesis, structural characterization and thermal properties of a new copper(II) one-dimensional coordination polymer based on bridging N,N'-bis(2 hydroxybenzylidene)-2,2-dimethylpropane-1,3-diamine and dicyanamide ligands. AB - The design and synthesis of polymeric coordination compounds of 3d transition metals are of great interest in the search for functional materials. The coordination chemistry of the copper(II) ion is of interest currently due to potential applications in the areas of molecular biology and magnetochemistry. A novel coordination polymer of Cu(II) with bridging N,N'-bis(2-hydroxyphenyl)-2,2 dimethylpropane-1,3-diamine (H2L-DM) and dicyanamide (dca) ligands, catena poly[[[MU2-2,2-dimethyl-N,N'-bis(2-oxidobenzylidene)propane-1,3-diamine 1:2kappa(6)O,N,N',O':O,O']dicopper(II)]-di-MU-dicyanamido 1:2'kappa(2)N(1):N(5);2:1'kappa(2)N(1):N(5)], [Cu2(C19H20N2O2)(C2N3)2]n, has been synthesized and characterized by CHN elemental analysis, IR spectroscopy, thermal analysis and X-ray single-crystal diffraction analysis. Structural studies show that the Cu(II) centres in the dimeric asymmetric unit adopt distorted square pyramidal geometries, as confirmed by the Addison parameter (tau) values. The chelating characteristics of the L-DM(2-) ligand results in the formation of a Cu(II) dimer with a double phenolate bridge in the asymmetric unit. In the crystal, the dimeric units are further linked to adjacent dimeric units through MU1,5-dca bridges to produce one-dimensional polymeric chains. PMID- 26846502 TI - Salt forms of the pharmaceutical amide dihydrocarbamazepine. AB - Carbamazepine (CBZ) is well known as a model active pharmaceutical ingredient used in the study of polymorphism and the generation and comparison of cocrystal forms. The pharmaceutical amide dihydrocarbamazepine (DCBZ) is a less well known material and is largely of interest here as a structural congener of CBZ. Reaction of DCBZ with strong acids results in protonation of the amide functionality at the O atom and gives the salt forms dihydrocarbamazepine hydrochloride {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5 yl)(hydroxy)methylidene]azanium chloride, C15H15N2O(+).Cl(-)}, dihydrocarbamazepine hydrochloride monohydrate {systematic name: [(10,11-dihydro 5H-dibenzo[b,f]azepin-5-yl)(hydroxy)methylidene]azanium chloride monohydrate, C15H15N2O(+).Cl(-).H2O} and dihydrocarbamazepine hydrobromide monohydrate {systematic name: [(10,11-dihydro-5H-dibenzo[b,f]azepin-5 yl)(hydroxy)methylidene]azanium bromide monohydrate, C15H15N2O(+).Br(-).H2O}. The anhydrous hydrochloride has a structure with two crystallographically independent ion pairs (Z' = 2), wherein both cations adopt syn conformations, whilst the two hydrated species are mutually isostructural and have cations with anti conformations. Compared to neutral dihydrocarbamazepine structures, protonation of the amide group is shown to cause changes to both the molecular (C=O bond lengthening and C-N bond shortening) and the supramolecular structures. The amide to-amide and dimeric hydrogen-bonding motifs seen for neutral polymorphs and cocrystalline species are replaced here by one-dimensional polymeric constructs with no direct amide-to-amide bonds. The structures are also compared with, and shown to be closely related to, those of the salt forms of the structurally similar pharmaceutical carbamazepine. PMID- 26846503 TI - A novel octanuclear nickel(II)-molybdenum(VI) heterometallic cluster based on the salicylhydroxamate ligand. AB - Salicylhydroxamic acid (H3shi) is known for its strong coordination ability and multiple coordination modes, and can easily coordinate to metal cations to form compounds with five- or six-membered rings, as well as mono-, di- and multinuclear compounds with interesting structures having potential applications in organic chemistry, coordination chemistry, and the materials and biological sciences. A novel octanuclear nickel(II)-molybdenum(VI) heterometallic cluster based on the salicylhydroxamate ligand, namely di-MU3-acetato-di-MU2-acetato-di MU3-hydroxido-di-MU3-oxido-tetraoxidooctakis(pyridine-kappaN)bis(MU5 salicylhydroxamato)hexanickel(II)dimolybdenum(VI) monohydrate, [Mo2Ni6(C7H4NO3)2(C2H3O2)4O5(OH)2(C5H5N)8].H2O, (I), was synthesized by the reaction of sodium molybdate, nickel acetate and salicylhydroxamic acid in a dimethylformamide/pyridine/methanol solution at room temperature. The salicylhydroxamate(3-) (shi(3-)), acetate and oxide ligands adopt complicated coordination modes and link six Ni(II) and two Mo(VI) cations into the octanuclear heterometallic cluster. All of the metal cations exhibit octahedral coordination geometries and are connected to each other through the sharing of corners, edges or planes. The heterometallic clusters are further connected to form two-dimensional supramolecular layers through weak C-H...O hydrogen bonds. Studies of the magnetic properties of the title compound reveal antiferromagnetic interactions between the Ni(II) cations. PMID- 26846504 TI - Synthesis and crystal structure of a two-dimensional sodium coordination polymer of 4,4'-(diazenediyl)bis(1H-1,2,4-triazol-5-one). AB - The crystal engineering of coordination polymers has aroused interest due to their structural versatility, unique properties and applications in different areas of science. The selection of appropriate ligands as building blocks is critical in order to afford a range of topologies. Alkali metal cations are known for their mainly ionic chemistry in aqueous media. Their coordination number varies depending on the size of the binding partners, and on the electrostatic interaction between the ligands and the metal ions. The two-dimensional coordination polymer poly[tetra-MU-aqua-[MU4-4,4'-(diazenediyl)bis(5-oxo-1H-1,2,4 triazolido)]disodium(I)], [Na2(C4H2N8O2)(H2O)4]n, (I), was synthesized from 4 amino-1H-1,2,4-triazol-5(4H)-one (ATO) and its single-crystal structure determined. The mid-point of the imino N=N bond of the 4,4'-(diazenediyl)bis(5 oxo-1H-1,2,4-triazolide) (ZTO(2-)) ligand is located on an inversion centre. The asymmetric unit consists of one Na(+) cation, half a bridging ZTO(2-) ligand and two bridging water ligands. Each Na(+) cation is coordinated in a trigonal antiprismatic fashion by six O atoms, i.e. two from two ZTO(2-) ligands and the remaining four from bridging water ligands. The Na(+) cation is located near a glide plane, thus the two bridging O atoms from the two coordinating ZTO(2-) ligands are on adjacent apices of the trigonal antiprism, rather than being in an anti configuration. All water and ZTO(2-) ligands act as bridging ligands between metal centres. Each Na(+) metal centre is bridged to a neigbouring Na(+) cation by two water molecules to give a one-dimensional [Na(H2O)2]n chain. The organic ZTO(2-) ligand, an O atom of which also bridges the same pair of Na(+) cations, then crosslinks these [Na(H2O)2]n chains to form two-dimensional sheets. The two dimensional sheets are further connected by intermolecular hydrogen bonds, giving rise to a stabile hydrogen-bonded network. PMID- 26846505 TI - Two cobalt(II) supramolecular isomers based on N,N'-bis(pyridin-3-yl)oxalamide induced by the molecular orientation of lattice DMF molecules. AB - Supramolecular isomerism for coordination networks refers to the existence of different architectures having the same building blocks and identical stoichiometries. For a given building block, different arrangements can lead to the formation of a series of supramolecular isomers. Two one-dimensional Co(II) coordination polymers based on N,N'-bis(pyridin-3-yl)oxalamide (BPO), both catena poly[[[dichloridocobalt(II)]-bis[MU-N,N'-bis(pyridin-3-yl)oxalamide kappa(2)N:N']] dimethylformamide disolvate], {[CoCl2(C12H10N4O2)2].2C3H7NO}n, have been assembled by the solvothermal method. Single-crystal X-ray diffraction analyses reveal that the two compounds are supramolecular isomers, the isomerism being induced by the orientation of the dimethylformamide (DMF) molecules in the crystal lattice. PMID- 26846507 TI - A phase II study of adjuvant S-1/cisplatin chemotherapy followed by S-1-based chemoradiotherapy for D2-resected gastric cancer. AB - PURPOSE: Surgery is the only possible curative treatment for gastric cancer. However, the high recurrence rate makes gastric cancer difficult to cure by surgery alone. The present study was conducted to evaluate the clinical outcomes and toxicity of adjuvant treatment, including S-1/cisplatin chemotherapy followed by radiotherapy with concurrent S-1. METHODS: Patients with radically D2-resected adenocarcinoma of the stomach of stage IB-IV (M0) were eligible. Patients were treated with S-1 (40-60 mg depending on the patient's body surface area) twice daily for 3 weeks and cisplatin (60 mg/m(2)) intravenously on day 1 every 5 weeks. Patients received CRT (45 Gy of radiation at 1.8 Gy/day, 5 days per week, for 5 weeks with the same dose of S-1 during radiation) followed by two additional cycles of S-1/cisplatin. The primary endpoint was the 3-year disease free survival (DFS) rate; the secondary endpoints were the 3-year overall survival rate and toxicities. RESULTS: Until May 2012, 46 patients were enrolled, and 34 (73.9%) completed the planned treatment. The median age was 53 years (range: 31-69 years), and the numbers of patients with stage IB, II, III and IV disease were 0, 17, 25 and 4, respectively. Main grade 3-4 toxicities were as follows: neutropenia (28.2%), nausea (17.4%), vomiting (8.7%) and anorexia (15.2%). At the time of analysis, after a median follow-up period of 56.5 months (3.03-74.0 months), 16 recurrence events and 15 deaths were reported. The estimated 3-year DFS and survival rates were 65.2 and 76.1%, respectively. The most common site of recurrence was the peritoneum (n = 12). CONCLUSIONS: The results of this phase II study show that intensified adjuvant treatment with S 1/cisplatin chemotherapy and S-1-based chemoradiotherapy was tolerable and effective in reducing disease recurrence. The addition of radiotherapy to chemotherapy may be effective in D2-resected gastric cancer. Although the data here are promising, a randomized trial is needed between patients treated with the current regimen and an appropriate comparator arm. PMID- 26846508 TI - Histone deacetylase 2 regulates doxorubicin (Dox) sensitivity of colorectal cancer cells by targeting ABCB1 transcription. AB - PURPOSE: Histone deacetylases (HDACs) have been shown to regulate cell cycle, differentiation, and apoptosis of colorectal cancer (CRC) cells, while their roles in drug sensitivity remain unclear. The objectives of the present study were to investigate the effects of HDAC2 on drug resistance of CRC cells. METHODS: We measured the expression of class I HDACs (HDAC1, 2, 3, 8) in CRC and human normal colonic epithelial cells. Additionally, we inhibited HDAC2 via siRNA or overexpressed it via pcDNA/HDAC2 transfection to evaluate its roles in doxorubicin (Dox) sensitivity. RESULTS: Our present study showed HDAC2 was significantly increased in CRC cell lines as compared to human normal colonic epithelial cells. Silencing of HDAC2 can obviously enhance the sensitivity of HCT 116 and SW480 cells to dDox. Further, knockdown of HDAC2 can significantly (p < 0.05) downregulate the expression of ABCB1, while not ABCG2, ABCC1, ABCA1, or ABCC2. Inhibition of HDAC2 decreased ABCB1 promoter activities and the phosphorylation of c-fos and c-Jun, which can directly interact with the ABCB1 promoter and then promote its transcription. Overexpression of HDAC2 by pcDNA/HDAC2 transfection significantly increased the sensitivity of CRC cells to Dox and upregulated the levels of P-gp, p-c-fos, and p-c-Jun. CONCLUSIONS: Our data revealed that HDAC2 can regulate Dox sensitivity of CRC cells by targeting ABCB1 transcription. It suggested that HDAC2 might be an important target for CRC therapy. Further, the combination of HDAC2-specific inhibitor and anticancer drugs including Dox might be an efficiency approach to elevate the treatment outcome of CRC. PMID- 26846506 TI - A Smartphone Application Supporting Recovery from Heroin Addiction: Perspectives of Patients and Providers in China, Taiwan, and the USA. AB - Smartphone-based interventions are increasingly used to support self-monitoring, self-management, and treatment and medication compliance in order to improve overall functioning and well-being. In attempting to develop a smartphone application (S-Health) that assists heroin-dependent patients in recovery, a series of focus groups (72 patients, 22 providers) were conducted in China, Taiwan, and the USA to obtain their perspectives on its acceptance and potential adoption. Data were analyzed according to the Diffusion of Innovation (DOI) theory of characteristics important to the adoption of innovation. Important to Relative Advantage, USA participants cited S-Health's potential ability to overcome logistical barriers, while those in China and Taiwan valued its potential to supplement currently limited services. In terms of Compatibility, participants across sites reported recovery needs and goals that such an application could be helpful in supporting; however, its utility during strong craving was questioned in China and Taiwan. Important factors relevant to Complexity included concerns about smartphone access and familiarity, individualization of content, and particularly in China and Taiwan, participants wanted assurance of privacy and security. The study results suggest a general acceptance, but also indicate cultural variations in access to therapeutic and other social support systems, legal repercussions of substance use, societal perceptions of addiction, and the role of family and other social support in recovery. Taking these factors into consideration is likely to increase diffusion as well as effectiveness of these smartphone-based interventions. PMID- 26846509 TI - Deception and Drug Acquisition: Correlates of "Success" Among Drug-Seeking Patients. AB - PURPOSE: Most research examining patient-based drug diversion neglects to assess physician deception directly. We attempt to determine if motives for deception are linked to success, and, similarly, if any health, demographic, or substance use history characteristics of the patients are predictive of being able to successfully deceive a physician. METHODS: Stratified random sampling was utilized to obtain a sample of 2349 young adults. Respondents completed a survey detailing their substance use histories and whether they had ever deceived a physician for medication. Ninety-three of these respondents reported attempting to deceive a physician for a medication and compose the analytic sample for the study. RESULTS: Of the 93 young adults who reported having attempted to deceive a physician for pharmaceuticals (4.0% of the general sample), 64 (68.8%) were successful. This included 24 only seeking medications for their own use, 9 only for financial purposes, and 31 with both motives. Respondents who reported recreationally using pharmaceuticals in the past were more likely to report successful attempts at obtaining a prescription compared with respondents without a history of abuse. With respect to demographic characteristics of the respondents, only race/ethnicity distinguished between successful attempts and failure. CONCLUSIONS: Although a rare occurrence in the overall sample, significant correlates of successful deception did emerge. Respondents motivated to obtain a prescription in order to sell it to others were overwhelmingly likely to succeed in their pursuit to deceive as compared with respondents who sought prescriptions for their own abuse. Successful deceivers were also more likely to have been legitimately prescribed medication in the past. Successful respondents were more likely to be Caucasian than any other race/ethnicity. PMID- 26846511 TI - The US Food and Drug Administration's New Regulatory Toolkit to Bring Medical Device Innovation Back to the United States. PMID- 26846510 TI - The peach HECATE3-like gene FLESHY plays a double role during fruit development. AB - Tight control of cell/tissue identity is essential for a correct and functional organ patterning, an important component of overall fruit development and eventual maturation and ripening. Despite many investigations regarding the molecular determinants of cell identity in fruits of different species, a useful model able to depict the regulatory networks governing this relevant part of fruit development is still missing. Here we described the peach fruit as a system to link the phenotype of a slow ripening (SR) selection to an altered transcriptional regulation of genes involved in determination of mesocarp cell identity providing insight toward molecular regulation of fruit tissue formation. Morpho-anatomical observations and metabolomics analyses performed during fruit development on the reference cultivar Fantasia, compared to SR, revealed that the mesocarp of SR maintained typical immaturity traits (e.g. small cell size, high amino acid contents and reduced sucrose) throughout development, along with a strong alteration of phenylpropanoid contents, resulting in accumulation of phenylalanine and lignin. These findings suggest that the SR mesocarp is phenotypically similar to a lignifying endocarp. To test this hypothesis, the expression of genes putatively involved in determination of drupe tissues identity was assessed. Among these, the peach HEC3-like gene FLESHY showed a strongly altered expression profile consistent with pit hardening and fruit ripening, generated at a post-transcriptional level. A double function for FLESHY in channelling the phenylpropanoid pathway to either lignin or flavour/aroma is suggested, along with its possible role in triggering auxin-ethylene cross talk at the start of ripening. PMID- 26846512 TI - Genetic divergence of tomato ringspot virus. AB - Tomato ringspot virus (ToRSV) has been detected in Chile, causing economically important diseases in a wide range of hosts. A ToRSV isolate was obtained from raspberry cv Heritage (Rasp-CL) showing leaf yellowing and stunting. The complete genome of Rasp-CL was sequenced by deep sequencing. The Rasp-CL RNA1 sequence shared 97.4 % nucleotide sequence identity with divergent RNA1 of isolate Rasp1 2014, while Rasp-CL RNA2 showed high divergence from all four isolates available in the database, sharing only 63.9-72.7 % nucleotide sequence identity. This difference was mainly based on the X4 coding region, which has been reported to be a high-variability region. Moreover, based on differences in the X4 region, three Rasp-CL RNA2 variants of different length were identified in the same host. One putative recombination event was identified between the Rasp-CL and GYV-2014 X4 genes. Phylogenetic analysis suggested that ToRSV isolates with currently available sequences form three distinct groups. Our results suggest that, for an accurate phylogenetic classification of ToRSV, it is necessary to obtain sequences of both RNAs. This is the first report of a complete ToRSV genome sequence from South America. PMID- 26846513 TI - Does this patient have VAP? PMID- 26846514 TI - Neces-SARI-ly? PMID- 26846515 TI - Understanding the passive leg raising test. PMID- 26846516 TI - ICU-acquired candidemia within SDD: low incidence in a 20-year longitudinal database. PMID- 26846517 TI - What's new in catheter-related infection: skin cleansing and skin antisepsis. PMID- 26846518 TI - Dealing with phthalates in medical devices: a case of primum non nocere (first do no harm)? PMID- 26846520 TI - Understanding clinical signs of poor tissue perfusion during septic shock. PMID- 26846519 TI - Pre-morbid glycemic control modifies the interaction between acute hypoglycemia and mortality. AB - PURPOSE: To study the impact of pre-morbid glycemic control on the association between acute hypoglycemia in intensive care unit (ICU) patients and subsequent hospital mortality in critically ill patients. METHODS: We performed a multicenter, multinational, retrospective observational study of patients with available HbA1c levels within the 3-month period preceding ICU admission. We separated patients into three cohorts according to pre-admission HbA1c levels (<6.5, 6.5-7.9, >=8.0%, respectively). Based on published data, we defined a glucose concentration of 40-69 mg/dL (2.2-3.8 mmol/L) as moderate hypoglycemia and <40 mg/dL (<2.2 mmol/L) as severe hypoglycemia. We applied logistic regression analysis to study the impact of pre-morbid glycemic control on the relationship between acute hypoglycemia and mortality. RESULTS: A total of 3084 critically ill patients were enrolled in the study. Among these patients, with increasing HbA1c levels from <6.5, to 6.5-7.9, and to >=8.0%, the incidence of both moderate (3.8, 11.1, and 16.4%, respectively; p < 0.001) and severe (0.9, 2.5, and 4.3%, respectively; p < 0.001) hypoglycemia progressively and significantly increased. The relationship between the occurrence of hypoglycemic episodes in the ICU and in-hospital mortality was independently and significantly affected by pre-morbid glucose control, as assessed by adjusted odds ratio (OR) and 95 % confidence interval (CI) for hospital mortality: (1) moderate hypoglycemia: in patients with <6.5, 6.5-7.9, and >=8.0 % of HbA1c level-OR 0.54, 95% CI 0.25-1.16; OR 0.82, 95 % CI 0.33-2.05; OR 3.42, 95 % CI 1.29-9.06, respectively; (2) severe hypoglycemia: OR 1.50, 95% CI 0.42-5.33; OR 1.59, 95% CI 0.36-7.10; OR 23.46, 95% CI 5.13-107.28, respectively (interaction with pre morbid glucose control, p = 0.009). We found that the higher the glucose level before admission to the ICU, the higher the mortality risk when patients experienced hypoglycemia. CONCLUSIONS: In critically ill patients, chronic pre morbid hyperglycemia increases the risk of hypoglycemia and modifies the association between acute hypoglycemia and mortality. PMID- 26846521 TI - Metabolic syndrome diagnosis and widespread high grade prostatic intraepithelial neoplasia significantly increase prostate cancer risk: results from a multicenter biopsy study. AB - BACKGROUND: To test in multicenter setting if patients affected of metabolic syndrome (MetS) and initial widespread high grade prostatic intraepithelial neoplasia (wHGPIN) diagnosis are at higher risk of prostate cancer (PCa) on repeat biopsy. METHODS: Patients clinical charts from three European Academic Hospital were reviewed in order to identify patients with initial diagnosis of HGPIN undergone to repeat biopsy. Inclusion and exclusion criteria were adopted to minimize patient heterogeneity. MetS was defined according to Word Heart Organization criteria while initial wHGPIN when >= 4 cores biopsy were involved. A multivariate logistic model was computed to assess the association between PCa and clinical-pathological variables. RESULTS: Overall 283 patients were scheduled. Median age was 67 years (IQR 62-72). MetS was diagnosed in 116/283 (41%) patients and PCa was detected in 84/283 (29.7%) patients. In particular, PCa was more frequently diagnosed in patients affected of wHGPIN and MetS (45/86, 52.3%) than in patients with wHGPIN and normal metabolic profile (28/95, 29.5%), p = 0.002. The multivariate logistic model confirmed that wHGPIN and MetS are independent risk factors for following PCa diagnosis, respectively OR 2.4 (95% CI 1.01-5.71, p = 0.04), OR 2.79 (95% CI 1.49-5.22, p = 0.01) while total PSA and DRE findings are not able to predict PCa at repeat biopsy, OR 1.05 (95% CI 0.98 1.03 p = 0.69) and OR 1.01 (95% CI 0.55-1.84, p = 0.96) respectively. CONCLUSIONS: wHGPIN is positively associated to PCa; assessing metabolic profile and repeat prostate biopsy is advisable in patients with initial diagnosis of wHGPIN. PMID- 26846523 TI - Editing of the Luteinizing Hormone Gene to Sterilize Channel Catfish, Ictalurus punctatus, Using a Modified Zinc Finger Nuclease Technology with Electroporation. AB - Channel catfish (Ictalurus punctatus) is the most important freshwater aquaculture species in the USA. Genetically enhanced fish that are sterile could both profit the catfish industry and reduce potential environmental and ecological risks. As the first step to generate sterile channel catfish, three sets of zinc finger nuclease (ZFN) plasmids targeting the luteinizing hormone (LH) gene were designed and electroporated into one-cell embryos, different concentrations were introduced, and the Cel-I assay was conducted to detect mutations. Channel catfish carrying the mutated LH gene were sterile, as confirmed by DNA sequencing and mating experiments. The overall mutation rate was 19.7 % for 66 channel catfish, and the best treatment was ZFN set 1 at the concentration 25 MUg/ml. To our knowledge, this is the first instance of gene editing of fish via plasmid introduction instead of mRNA microinjection. The introduction of the ZFN plasmids may have reduced mosaicism, as mutated individuals were gene edited in every tissue evaluated. Apparently, the plasmids were eventually degraded without integration, as they were not detectable in mutated individuals using PCR. Carp pituitary extract failed to induce spawning and restoration of fertility, indicating the need for developing other hormone therapies to achieve reversal of sterility upon demand. This is the first sterilization achieved using ZFN technology in an aquaculture species and the first successful gene editing of channel catfish. Our results will help understand the roles of the LH gene, purposeful sterilization of teleost fishes, and is a step towards control of domestic, hybrid, exotic, invasive, and transgenic fishes. PMID- 26846525 TI - Lateral geniculate atrophy in Parkinson's with visual hallucination: A trans synaptic degeneration? AB - INTRODUCTION: Defective visual information processing contributes to visual hallucination in PD, for which "top-down" and "bottom-up" impairment are suggested mechanisms. This study was aimed to investigate macro- and microstructural neural changes in afferent visual pathways in relation to visual hallucination in nondemented PD patients. METHODS: This study included 24 nondemented, nondepressed PD patients (10 hallucinating and 14 nonhallucinating) and 15 age-matched healthy controls. We analyzed volumetric and diffusion tensor MRI data by applying region of interest analyses on the visual pathways, including the optic chiasm, bilateral optic nerves, lateral geniculate bodies, optic radiations, and primary visual cortex. RESULTS: Patients' demographic characteristics, daily medication doses, as well as duration and motor severity of PD were similar in the two PD groups. Compared to PD patients without hallucination, those with hallucination had fractional anisotropy decrease in the left optic nerve and showed atrophy of lateral geniculate bodies, especially in the left side. In addition, the PD with hallucination group had diffusivity increase in the left optic radiation compared to that in the PD without hallucination and healthy control groups. There were no differences in the primary visual cortex volume among the study groups. CONCLUSIONS: We found microstructural alterations in visual pathways in nondemented PD patients with hallucination, mainly in first-order neurons and atrophy in the lateral geniculate body where the retinal ganglion cells synapse to second-order neurons. Afferent visual pathway degeneration may occur in a trans-synaptic way in PD. Further studies warrant to be conducted. PMID- 26846524 TI - Intraspecific Variation in Mitogenomes of Five Crassostrea Species Provides Insight into Oyster Diversification and Speciation. AB - A large number of Crassostrea oysters are found in Asia-Pacific. While analyses of interspecific variation have helped to establish historical relationships among these species, studies on intraspecific variation are necessary to understand their recent evolutionary history and current forces driving population biology. We resequenced 18 and analyzed 31 mitogenomes of five Crassostrea species from China: Crassostrea gigas, Crassostrea angulata, Crassostrea sikamea, Crassostrea ariakensis, and Crassostrea hongkongensis. Our analysis finds abundant insertions, deletions, and single-nucleotide polymorphisms in all species. Intraspecific variation varies greatly among species with polymorphic sites ranging from 54 to 293 and nucleotide diversity ranging from 0.00106 to 0.00683. In all measurements, C. hongkongensis that has the narrowest geographic distribution exhibits the least sequence diversity; C. ariakensis that has the widest distribution shows the highest diversity, and species with intermediate distribution show intermediate levels of diversity. Low sequence diversity in C. hongkongensis may reflect recent bottlenecks that are probably exacerbated by human transplantation. High diversity in C. ariakensis is likely due to divergence of northern and southern China populations that have been separated without gene flow. The significant differences in mitogenome diversity suggest that the five sister species of Crassostrea have experienced different evolutionary forces since their divergence. The recent divergence of two C. ariakensis populations and the C. gigas/angulata species complex provides evidence for continued diversification and speciation of Crassostrea species along China's coast, which are shaped by unknown mechanisms in a north-south divide. PMID- 26846526 TI - Technical flaws in multiple-choice questions in the access exam to medical specialties ("examen MIR") in Spain (2009-2013). AB - BACKGROUND: The main factor that determines the selection of a medical specialty in Spain after obtaining a medical degree is the MIR ("medico interno residente", internal medical resident) exam. This exam consists of 235 multiple-choice questions with five options, some of which include images provided in a separate booklet. The aim of this study was to analyze the technical quality of the multiple-choice questions included in the MIR exam over the last five years. METHODS: All the questions included in the exams from 2009 to 2013 were analyzed. We studied the proportion of questions including clinical vignettes, the number of items related to an image and the presence of technical flaws in the questions. For the analysis of technical flaws, we adapted the National Board of Medical Examiners (NBME) guidelines. We looked for 18 different issues included in the manual, grouped into two categories: issues related to testwiseness and issues related to irrelevant difficulties. RESULTS: The final number of questions analyzed was 1,143. The percentage of items based on clinical vignettes increased from 50% in 2009 to 56-58% in the following years (2010-2013). The percentage of items based on an image increased progressively from 10% in 2009 to 15% in 2012 and 2013. The percentage of items with at least one technical flaw varied between 68 and 72%. We observed a decrease in the percentage of items with flaws related to testwiseness, from 30% in 2009 to 20% in 2012 and 2013. While most of these issues decreased dramatically or even disappeared (such as the imbalance in the correct option numbers), the presence of non-plausible options remained frequent. With regard to technical flaws related to irrelevant difficulties, no improvement was observed; this is especially true with respect to negative stem questions and "hinged" questions. CONCLUSION: The formal quality of the MIR exam items has improved over the last five years with regard to testwiseness. A more detailed revision of the items submitted, checking systematically for the presence of technical flaws, could improve the validity and discriminatory power of the exam, without increasing its difficulty. PMID- 26846522 TI - Multicentric randomized clinical trial to evaluate the long-term effectiveness of a motivational intervention against smoking, based on the information obtained from spirometry in primary care: the RESET study protocol. AB - BACKGROUND: Spirometry is the recommended method of evaluating pulmonary function when respiratory disease is suspected in smokers. Nonetheless, no evidence exists of the usefulness of information obtained from this test as a motivational strategy for smoking cessation. The primary objective of this study is to evaluate the effectiveness of a motivational intervention based on spirometry results in achieving long-term smoking cessation. METHODS/DESIGN: We propose a multicenter randomized clinical trial in the primary care setting. STUDY SUBJECTS: We will recruit active smokers of both sexes, aged 35-70 years, with a cumulated smoking habit exceeding 10 packs/year and who consult for any reason with their primary care physician in the 20 health centers in the province of Tarragona (Spain). Patients with a history of lung disease or who have undergone exploratory measures of pulmonary function in the preceding 12 months will be excluded. All patients who agree to participate will provide signed informed consent prior to their inclusion. A total of 1000 smokers will be consecutively randomized to a control or intervention group (1:1). INTERVENTION: Participants in both groups will receive brief (5-minute) health counseling, in accordance with usual clinical practice. In a consultation lasting about 15 minutes, participants in the intervention group will also receive detailed, personalized information about the results of a spirometry test and about their lung age compared with their chronological age. Both groups will be followed up for 12 months. Main variables and analysis: The main variable will be sustained smoking abstinence at 12 months after the intervention, as confirmed by CO breath testing and urine cotinine test. Results will be analyzed based on intention to treat, using the chi-square test and logistical regression if necessary to adjust for confounding variables. DISCUSSION: We expect the rate of prolonged smoking abstinence in the intervention group will be at least 5% higher than in the control group. If this strategy proves effective, it could easily be included in the health promotion activities offered in primary care settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02153047 . Registered on 28/05/2014. PMID- 26846528 TI - CT Lung Cancer Screening. PMID- 26846529 TI - Implementing a Community Hospital Lung Cancer Screening Program: A Multidisciplinary Program and a Standardized Reporting System. PMID- 26846527 TI - Echo-Doppler-derived indexes of ventricular stiffness and ventriculo-arterial interaction as predictors of new-onset atrial fibrillation in patients with heart failure. AB - BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF) and worsens their prognosis. Vulnerability to changes in loading is an important factor in the development of AF and is strongly influenced by ventricular stiffness and ventriculo-arterial interaction. The aim of this study was to investigate predictors of AF development in patients with HF. METHODS: We studied 349 patients with stable HF. The following parameters of ventricular stiffness and ventriculo-arterial interaction were derived from echo-Doppler measurements: left ventricular (LV) diastolic elastance (Ed), effective arterial elastance (Ea), LV end-systolic elastance (Ees) and ventricular-vascular coupling index (VVI). RESULTS: AF occurred in 57 (16.3%) patients over a median follow up of 30.3 months. Echo-Doppler-derived parameters of ventricular stiffness and ventriculo-arterial interaction were closely associated with HF severity. Ed was independently associated with AF after adjustment for age, hypertension, diabetes mellitus, and left atrial volume index (hazard ratio [HR] 5.49, p = 0.018). Ea and VVI were also associated with new-onset AF (HR 1.66, p = 0.027, and HR 1.06, p = 0.001, respectively). CONCLUSIONS: Echo-Doppler indexes of ventricular stiffness are closely associated with HF severity. LV diastolic elastance (Ed) is the strongest predictor of new-onset AF in HF patients. PMID- 26846530 TI - Follow-up of Incidental Pulmonary Nodules and the Radiology Report. AB - PURPOSE: Incidental pulmonary nodules that require follow-up are often noted on chest CT. Evidence-based guidelines regarding appropriate follow-up have been published, but the rate of adherence to guideline recommendations is unknown. Furthermore, it is unknown whether the radiology report affects the nodule follow up rate. METHODS: A review of 1,000 CT pulmonary angiographic studies ordered in the emergency department was performed to determine the presence of an incidental pulmonary nodule. Fleischner Society guidelines were applied to ascertain if follow-up was recommended. Radiology reports were classified on the basis of whether nodules were listed in the findings section only, were noted in the impression section, or had explicit recommendations for follow-up. Whether the rate of nodule follow-up was affected by the radiology report was determined according to these 3 groups. RESULTS: Incidental pulmonary nodules that required follow-up were noted on 9.9% (95% confidence interval, 8%-12%) of CT pulmonary angiographic studies. Follow-up for nodules was poor overall (29% [28 of 96]; 95% confidence interval, 20%-38%) and decreased significantly when the nodules were mentioned in the findings section only (0% [0 of 12]). Specific instructions to follow up nodules in radiology reports still resulted in a low follow-up rate of 29% (19 of 65; 95% confidence interval, 18%-40%). CONCLUSIONS: Incidental pulmonary nodules detected on CT pulmonary angiography are common and are frequently not followed up appropriately. Although the inclusion of a pulmonary nodule in the impression section of a radiology report is helpful, it does not ensure follow-up. Better systems for appropriate identification and follow-up of incidental findings are needed. PMID- 26846531 TI - Controversies in Lung Cancer Screening. AB - There remains an extensive debate over lung cancer screening, with lobbying for and against screening for very compelling reasons. The National Lung Screening Trial, International Early Lung Cancer Program, and other major screening studies favor screening with low-dose CT scans and have shown a reduction in lung cancer specific mortality. The increasing incidence of lung cancer and the dismal survival rate for advanced disease despite improved multimodality therapy have sparked an interest in the implementation of national lung cancer screening. Concerns over imaging workflow, radiation dose, management of small nodules, overdiagnosis bias, lead-time and length-time bias, emerging new technologies, and cost-effectiveness continue to be debated. The authors address each of these issues as they relate to radiologic practice. PMID- 26846532 TI - Performance of ACR Lung-RADS in a Clinical CT Lung Screening Program. AB - PURPOSE: The aim of this study was to assess the effect of applying ACR Lung-RADS in a clinical CT lung screening program on the frequency of positive and false negative findings. METHODS: Consecutive, clinical CT lung screening examinations performed from January 2012 through May 2014 were retroactively reclassified using the new ACR Lung-RADS structured reporting system. All examinations had initially been interpreted by radiologists credentialed in structured CT lung screening reporting following the National Comprehensive Cancer Network's Clinical Practice Guidelines in Oncology: Lung Cancer Screening (version 1.2012), which incorporated positive thresholds modeled after those in the National Lung Screening Trial. The positive rate, number of false-negative findings, and positive predictive value were recalculated using the ACR Lung-RADS-specific positive solid/part-solid nodule diameter threshold of 6 mm and nonsolid (ground glass) threshold of 2 cm. False negatives were defined as cases reclassified as benign under ACR Lung-RADS that were diagnosed with malignancies within 12 months of the baseline examination. RESULTS: A total of 2,180 high-risk patients underwent baseline CT lung screening during the study interval; no clinical follow-up was available in 577 patients (26%). ACR Lung-RADS reduced the overall positive rate from 27.6% to 10.6%. No false negatives were present in the 152 patients with >12-month follow-up reclassified as benign. Applying ACR Lung-RADS increased the positive predictive value for diagnosed malignancy in 1,603 patients with follow-up from 6.9% to 17.3%. CONCLUSIONS: The application of ACR Lung-RADS increased the positive predictive value in our CT lung screening cohort by a factor of 2.5, to 17.3%, without increasing the number of examinations with false-negative results. PMID- 26846533 TI - ACR CT Accreditation Program and the Lung Cancer Screening Program Designation. AB - The ACR recognizes that low-dose CT for lung cancer screening has the potential to significantly reduce mortality from lung cancer in the appropriate high-risk population. The ACR supports the recommendations of the US Preventive Services Task Force and the National Comprehensive Cancer Network for screening patients. To be effective, lung cancer screening should be performed at sites providing high-quality low-dose CT examinations overseen and interpreted by qualified physicians using a structured reporting and management system. The ACR has developed a set of tools necessary for radiologists to take the lead on the front lines of lung cancer screening. The ACR Lung Cancer Screening Center designation is built upon the ACR CT accreditation program and requires use of Lung-RADS or a similar structured reporting and management system. This designation provides patients and referring providers with the assurance that they will receive high quality screening with appropriate follow-up care. PMID- 26846534 TI - US Preventive Services Task Force CT Lung Cancer Screening Recommendations: Community Awareness and Perceptions. PMID- 26846535 TI - The Radiologist as Direct Public Educator: Impact of Sessions Demystifying Select Cancer Screening Imaging Examinations. AB - PURPOSE: The aim of this report is to describe our early experience with radiologist-led direct public education about imaging-based cancer screening examinations, with a focus on the level of satisfaction and the educational impact reported by session participants. METHODS: Subspecialty radiologists provided 1-hour educational sessions to small lay public audiences covering breast, prostate, and lung cancer screening, focusing on key radiologic screening tests. Subsequently, session participants completed a survey pertaining to their levels of satisfaction and the perceived impact of the sessions on knowledge of the diseases and relevant screening tests; results from all topic sessions were pooled for analysis. RESULTS: One hundred nineteen participants attended a total of 144 sessions. The large majority of respondents agreed or strongly agreed that the sessions increased their understanding (95.4%), they gained information not obtained from clinic visit (88.1%), seeing radiology images helped their understanding (92.6%), they felt more involved in their own care (85.8%), they felt more prepared to undergo screening tests (87.4%), they were satisfied with the sessions' format (93.3%) and content (96.2%), their main questions were answered (88.3%), they would be interested in similar future radiologist-led sessions (88.5%), and they would recommend the sessions to friends (93.9%). The provided information (43.1%) and images (34.7%) were identified as the most helpful aspects of the sessions. CONCLUSION: Radiologist-led direct public education sessions about imaging-based cancer screening examinations yield high levels of audience satisfaction and add value to the public's understanding of the role of radiology and radiologists. Our experience may provide an encouraging model for other radiology practices in pursuing similar endeavors. PMID- 26846536 TI - Experience With a CT Screening Program for Individuals at High Risk for Developing Lung Cancer. AB - PURPOSE: The aim of this study was to compare results of National Comprehensive Cancer Network (NCCN) high-risk group 2 with those of NCCN high-risk group 1 in a clinical CT lung screening program. METHODS: The results of consecutive clinical CT lung screening examinations performed from January 2012 through December 2013 were retrospectively reviewed. All examinations were interpreted by radiologists credentialed in structured CT lung screening reporting, following the NCCN Clinical Practice Guidelines in Oncology: Lung Cancer Screening (version 1.2012). Positive results required a solid nodule >=4 mm, a ground-glass nodule >=5 mm, or a mediastinal or hilar lymph node >1 cm, not stable for >2 years. Significant incidental findings and findings suspicious for pulmonary infection were also recorded. RESULTS: A total of 1,760 examinations were performed (464 in group 2, 1,296 in group 1); no clinical follow-up was available in 432 patients (28%). Positive results, clinically significant incidental findings, and suspected pulmonary infection were present in 25%, 6%, and 6% in group 2 and 28.2%, 6.2%, and 6.6% in group 1, respectively. Twenty-three cases of lung cancer were diagnosed (6 in group 2, 17 in group 1), for annualized rates of malignancy of 1.8% in group 2 and 1.6% in group 1. CONCLUSION: NCCN group 2 results were substantively similar to those for group 1 and closely resemble those reported in the National Lung Screening Trial. Similar rates of positivity and lung cancer diagnosis in both groups suggest that thousands of additional lives may be saved each year if screening eligibility is expanded to include this particular high risk group. PMID- 26846538 TI - Improving the performance of an aerobic membrane bioreactor (MBR) treating pharmaceutical wastewater with powdered activated carbon (PAC) addition. AB - In this study, the effects of organic loading rate (OLR) and the addition of powdered activated carbon (PAC) on the performance and membrane fouling of MBR were conducted to treat real pharmaceutical process wastewater. Over 145 days of operation, the MBR system was operated at OLRs ranging from 1 to 2 kg COD m(-3) day(-1) without sludge wasting. The addition of PAC provided an improvement in the flux, despite an increase in the OLR:PAC ratio. The results demonstrated that the hybrid PAC-MBR system maintained a reduced amount of membrane fouling and steadily increased the removal performance of etodolac. PAC addition reduced the deposition of extracellular polymeric substance and organic matter on the membrane surface and resulted an increase in COD removal even at higher OLRs with low PAC addition. Membrane fouling mechanisms were investigated using combined adsorption fouling models. Modified fouling index values and normalized mass transfer coefficient values indicated that predominant fouling mechanism was cake adsorption. PMID- 26846537 TI - Ex situ product recovery for enhanced butanol production by Clostridium beijerinckii. AB - In situ butanol recovery fermentation has been intensively studied as an effective alternative to conventional butanol production, which is limited due to the cellular toxicity of butanol. However, the low biocompatibility of adsorbents often leads to failure of in situ recovery fermentations. In this study, Clostridium beijerinckii NCIMB 8052 was cultured in flasks without shaking and in situ recovery fermentation was performed by using an adsorbent L493. The amounts of acetone, butanol, and ethanol (ABE) increased by 34.4 % in the presence of the adsorbent. In contrast, cell growth and production of organic acids and ABE were retarded in the 7-L batch fermentations with in situ butanol recovery. Cell damage occurred in the fermentor upon agitation in the presence of the adsorbent, unlike in static flask cultures with in situ recovery. Ex situ recovery fermentation using circulation of fermentation broth after mid-exponential phase of cell growth was developed to avoid adsorbent-cell incompatibility. No apparent cell damage was observed and 25.7 g/L of ABE was produced from 86.2 g/L glucose in the fed-batch mode using 7 L fermentors. Thus, ex situ recovery fermentation with C. beijerinckii is effective for enhancing butanol fermentation. PMID- 26846539 TI - Telmisartan in the diabetic murine model of acute myocardial infarction: dual contrast manganese-enhanced and delayed enhancement MRI evaluation of the peri infarct region. AB - BACKGROUND: A novel MRI technique, employing dual contrast manganese-enhanced MRI (MEMRI) and delayed enhancement MRI (DEMRI), can evaluate the physiologically unstable peri-infarct region. Dual contrast MEMRI-DEMRI enables comprehensive evaluation of telmisartan to salvage the peri-infarct injury to elucidate the underlying mechanism of restoring the ischemic cardiomyopathy in the diabetic mouse model. METHODS AND RESULTS: Dual contrast MEMRI-DEMRI was performed on weeks 1, 2, and 4 following initiation of telmisartan treatment in 24 left anterior descendent artery ligated diabetic mice. The MRI images were analyzed for core infarct, peri-infarct, left ventricular end-diastolic, end-systolic volumes, and the left ventricular ejection fraction (LVEF). Transmission electron microscopy (TEM) and real-time PCR were used for ex vivo analysis of the myocardium. Telmisartan vs. control groups demonstrated significantly improved LVEF at weeks 1, 2, and 4, respectively (33 +/- 7 %*** vs. 19 +/- 5 %, 29 +/- 3 %*** vs. 22 +/- 4 %, and 31 +/- 2 %*** vs 18 +/- 6 %, ***p < 0.001). The control group demonstrated significant differences in the scar volume measured by MEMRI and DEMRI, demonstrating peri-infarct injury. Telmisartan group significantly salvaged the peri-infarct injury. The myocardial effects were validated by TEM, which confirmed the presence of the injured but viable cardiomyocyte morphology in the peri-infarct region and by flow cytometry of venous blood, which demonstrated significantly increased circulating endothelial progenitor cells (EPCs). CONCLUSION: The improved cardiac function in ischemic cardiomyopathy of diabetic mice by telmisartan is attributed to the attenuation of the peri-infarct injury by the angiogenic effects of EPCs to salvage the injured cardiomyocytes. Dual-contrast MEMRI-DEMRI technique tracked the therapeutic effects of telmisartan on the injured myocardium longitudinally. PMID- 26846541 TI - Clinical and Electromyographic Characteristics of Unilateral Vocal Fold Paralysis With Lower Cranial Nerve Injury. AB - OBJECTIVES: The aim was to investigate the clinical and electromyographic characteristics of patients with unilateral vocal fold paralysis (UVFP) combined with lower cranial nerve injury. STUDY DESIGN: This is a case series with chart review. METHODS: Among 368 patients with idiopathic UVFP, 31 patients (8.4%) were eventually diagnosed with lower cranial nerve palsy after examinations of the head and neck, radiology, and electromyogram (EMG). The clinical and electromyographic characteristics of these patients were analyzed. RESULTS: Of the 31 patients, 27 patients exhibited obvious abnormal lower cranial nerve injury physical signs, and 4 patients showed atypical physical signs, identified by EMG. Ultimately, 41.9% (13/31) were diagnosed with idiopathic causes, 38.7% (12/31) with intracranial or skull-base lesions on radiology, 12.9% (4/31) with lower cranial neuritis, and 6.4% (2/31) with radiation-induced lower cranial nerve palsy. Among the cranial lesions, lesions of the jugular foramen region were the most common (50%, 6/12). All 26 patients who underwent EMG tests were confirmed to have vagus nerve impairments (11 complete and 15 incomplete) and accessory nerve impairments (16 complete and 10 incomplete), whereas only 13 patients (50%) exhibited hypoglossal nerve injuries (5 complete and 8 incomplete). CONCLUSIONS: For patients with clinically "idiopathic" UVFP, physical examinations of the lower cranial nerves are essential screening procedures. For patients with abnormal or suspicious physical signs, radiology should be performed to detect possible cranial or cervical lesions. EMG tests were strongly recommended to identify suspicious lower cranial nerve injury and its severity, and may help to predict the prognosis. PMID- 26846540 TI - Circular RNA in blood corpuscles combined with plasma protein factor for early prediction of pre-eclampsia. AB - OBJECTIVE: To determine the expression of circular RNA (circRNA) in blood corpuscles of pregnant women before 20 weeks of pregnancy and to create a new model to identify the performance of circRNA combined with protein factors for the early diagnosis of pre-eclampsia (PE). DESIGN: Nested case-control study. SETTING: University medical centre, Guangzhou, China. POPULATION: A total of 1400 pregnant women recruited between 8 and 20 weeks of gestation. In all, 41 women with PE were included in the study, and were matched with 41 normally pregnant women based on maternal age and gestational age at same-size ratio. METHODS: The samples were analysed using a human circRNA microarray in the discovery phase, then the circRNA and the plasma protein factor endoglin (ENG) were validated. Finally we combined ENG with circRNA to create a new early prediction model for PE. MAIN OUTCOME MEASURES: Early changes of circRNA and ENG in PE. RESULTS: The circ_101222 levels in blood corpuscles of patients with PE were significantly higher than those in corresponding healthy women (P < 0.001). Using ENG in combination with circ_101222 resulted in a sensitivity of 0.7073, a specificity of 0.8049, and overall area under the curve of 0.876 (95% confidence interval 0.816-0.922) for the prediction of PE. CONCLUSION: CircRNA and plasma proteins may have some predictive value for PE (such as circ_101222 and ENG). The performance of each of these factors may be strengthened when plasma proteins are used in combination with circRNA. The results are preliminary and need to be validated in larger studies and other populations. TWEETABLE ABSTRACT: Plasma protein endoglin in combination with circ_101222 strengthened the predictive power for pre-eclampsia. PMID- 26846542 TI - Acoustic Characteristics of Voice Before and After Endoscopic Partial Laryngectomy in Early Glottic Cancer. AB - OBJECTIVES: To evaluate the voice changes after narrow-margin endoscopic partial laryngectomy in subjects with T1N0M0 glottic cancer. STUDY DESIGN: Uncontrolled retrospective comparison of preoperative and postoperative mean phonation time; fundamental frequency, jitter, shimmer, and noise-to-harmonic ratio; and voice related quality of life (V-RQOL) survey scores. METHODS: Seventeen adults diagnosed with T1N0M0 glottic cancer who underwent narrow-margin endoscopic partial laryngectomy were included. All subjects had preoperative and postoperative acoustic evaluation and V-RQOL scores. Subjects were separated into three groups based on age and depth of resection. Group A (mean age, 52 years) consisted of seven subjects who underwent superficial resection (superficial layer of lamina propria) and were younger than 60 years. Group B (mean age, 76 years) consisted of six subjects who were older than 60 years and underwent superficial resection (superficial layer of lamina propria). The four subjects in group C were older than 60 years and underwent deep resection (into the vocal ligament and/or into the thyroarytenoid muscle). RESULTS: There was a statistically significant improvement in V-RQOL in group A. The acoustic measures did not change after surgery (no P<0.05). CONCLUSION: For early-stage cancer, patients younger than 60 years and superficial resection of cancer are predictive for better voice. PMID- 26846543 TI - An iOS-based Cepstral Peak Prominence Application: Feasibility for Patient Practice of Resonant Voice. AB - OBJECTIVES/HYPOTHESIS: Patients participating in voice therapy often express difficulty replicating therapy targets during their independent home practice. To assist patients, an iOS-based app was developed that calculates and displays cepstral peak prominence (CPP) values for patient self-monitoring of voice quality. The purpose of this study was to investigate the usability (ie ease of use) and utility (ie helpfulness) of this app in patient practice of resonant voice, and its effect on self-efficacy for practice. DESIGN: This study used mixed methods including repeated measures, survey, and semi-structured interview. METHODS/RESULTS: A total of 14 individuals undergoing voice therapy for a variety of voice disorders produced sustained phonation and connected speech tasks in three sequential conditions: habitual voice quality, resonant voice quality achieved without clinician assistance, and resonant voice quality achieved in interaction with the CPP app. For both tasks, CPP values were significantly and progressively higher in subsequent conditions, indicating utility of mobile CPP to differentiate habitual voice quality from resonant voice production. The participants found the app easy to use as indicated by high System Usability Scale ratings, and rated self-efficacy for practice with the app significantly higher than for unassisted practice. The interviews suggested that the participants found numeric CPP feedback helpful in self-evaluating voice quality, and thought it was "fun" to use the app. CONCLUSION: CPP information provided on a mobile app has potential to assist and motivate patients in the achievement of resonant voice production. PMID- 26846544 TI - Does Tonsillectomy Affect Voice in Early or Late Postoperative Periods in Adults? AB - OBJECTIVE: The aim of our study was to investigate the short- and long-term effects of tonsillectomy on voice performance in adults. STUDY DESIGN: Prospective cohort study. MATERIALS AND METHODS: This study was conducted between January 2013 and June 2015. A total of 26 adults who had tonsillectomy due to chronic tonsillitis or recurrent acute tonsillitis were included in the study. The voice performances of the participants were analyzed with objective and subjective methods before surgery, and 1 and 3 months after surgery. An acoustic voice analysis (fundamental frequency [F0], jitter %, shimmer %) was performed for objective analysis, and Voice Handicap Index survey was used for subjective analysis of the voice. Preoperative F0, jitter %, shimmer %, and Voice Handicap Index values were compared with the values obtained 1 and 3 months after surgery. RESULTS: Impairment of voice performance was determined when preoperative and postoperative first month F0, jitter %, and shimmer % values were compared. Three months after surgery, those values were found similar to the preoperative values. CONCLUSION: Tonsillectomy affects voice performance negatively in adults in short term; however, it does not affect voice performance in long term after surgery. PMID- 26846545 TI - Correlates of emotional and behavioural problems in children with perinatally acquired HIV in Cape Town, South Africa. AB - In the antiretroviral era, youth perinatally infected with HIV (PHIV+) are surviving into adulthood and are at risk for emotional and behavioural problems. Few studies of these problems have been conducted in low- and middle-income countries and even fewer in sub-Saharan Africa. The aims of this study were to provide a quantitative description of emotional and behavioural problems in a group of PHIV+ youth (n = 78) in South Africa compared with a group of demographically matched HIV-negative controls (n = 30) and to identify correlates of emotional and behavioural problems. A cross-sectional study was conducted employing participants from community and hospital-based clinics. Emotional and behavioural problems were assessed using the Child Behaviour Checklist (CBCL). Several measures were used to assess demographic, biological, cognitive and contextual correlates of problem behaviours. Youth were compared by HIV status on demographic, cognitive and contextual variables as well as the Total Problems and subscale scores of the CBCL. Multivariate comparisons of the influence of contextual and cognitive variables on CBCL Total Problems scores were performed using a stepwise linear regression analytic procedure. In this study, there were no significant differences in between-group comparisons for the prevalence of Internalizing, Externalizing and Total Problems in the PHIV+ youth and control group at the clinical and borderline cut-off ranges of the CBCL. Caregiver depression was the only significant predictor of greater Total Problems scores in the full model, after controlling for age and gender (F = 8.57, df = 5.102, P < .01). An interaction between HIV status and caregiver depression was observed (t = -2.20, P = .03), with follow-up within-group analyses confirming that caregiver depression predicted greater Total Problems scores both in HIV-negative youth (beta = 0.61, P < .001), and to a lesser extent, in HIV-positive youth (beta = 0.25, P < .001). This study highlights the need for adequate screening of depression in the caregivers of HIV-infected youth. PMID- 26846546 TI - Is deep neuromuscular block beneficial in laparoscopic surgery? No, probably not. AB - BACKGROUND: There is currently a controversy regarding the need for and clinical benefit of maintaining deep neuromuscular block (post-tetanic counts of 1 or 2) vs. moderate block (train-of-four counts of 1-3) for routine laparoscopic surgery. Two recent review articles on this subject arrived at rather different conclusions. This manuscript is part of Pro/Con debate from the authors of these two reviews. METHODS: The authors of the Pro and Con sides of the debate had the opportunity to read each other manuscripts and worked from the same basic database of references. RESULTS: The present authors could find only one peer reviewed paper which presented objective evidence supporting the proposition that deep neuromuscular block provides superior operating conditions for the surgeon during laparoscopic surgery. CONCLUSION: There is not enough good evidence available to justify the routine use of deep neuromuscular block for laparoscopic surgery and the associated expense of high-dose sugammadex. PMID- 26846547 TI - A short period of high-intensity interval training improves skeletal muscle mitochondrial function and pulmonary oxygen uptake kinetics. AB - The aim of the present study was to examine whether improvements in pulmonary oxygen uptake (Vo2) kinetics following a short period of high-intensity training (HIT) would be associated with improved skeletal muscle mitochondrial function. Ten untrained male volunteers (age 26 +/- 2 yr; mean +/- SD) performed six HIT sessions (8-12 * 60 s at incremental test peak power; 271 +/- 52 W) over a 2-wk period. Before and after the HIT period, Vo2 kinetics was modeled during moderate intensity cycling (110 +/- 19 W). Mitochondrial function was assessed with high resolution respirometry (HRR), and maximal activities of oxidative enzymes citrate synthase (CS) and cytochrome c oxidase (COX) were accordingly determined. In response to HIT, Vo2 kinetics became faster (tau: 20.4 +/- 4.4 vs. 28.9 +/- 6.1 s; P < 0.01) and fatty acid oxidation (ETFP) and leak respiration (LN) both became elevated (P < 0.05). Activity of CS and COX did not increase in response to training. Both before and after the HIT period, fast Vo2 kinetics (low tau values) was associated with large values for ETFP, electron transport system capacity (ETS), and electron flow specific to complex II (CIIP) (P < 0.05). Collectively, these findings support that selected measures of mitochondrial function obtained with HRR are important for fast Vo2 kinetics and better markers than maximal oxidative enzyme activity in describing the speed of the Vo2 response during moderate-intensity exercise. PMID- 26846548 TI - Heat stress redistributes blood flow in arteries of the brain during dynamic exercise. AB - We hypothesized that heat stress would decrease anterior and posterior cerebral blood flow (CBF) during exercise, and the reduction in anterior CBF would be partly associated with large increase in extracranial blood flow (BF). Nine subjects performed 40 min of semirecumbent cycling at 60% of the peak oxygen uptake in hot (35 degrees C; Heat) and thermoneutral environments (25 degrees C; Control). We evaluated BF and conductance (COND) in the external carotid artery (ECA), internal carotid artery (ICA), and vertebral artery (VA) using ultrasonography. During the Heat condition, ICA and VA BF were significantly increased 10 min after the start of exercise (P < 0.05) and thereafter gradually decreased. ICA COND was significantly decreased (P < 0.05), whereas VA COND remained unchanged throughout Heat. Compared with the Control, either BF or COND of ICA and VA at the end of Heat tended to be lower, but not significantly. In contrast, ECA BF and COND at the end of Heat were both higher than levels in the Control condition (P < 0.01). During Heat, a reduction in ICA BF appears to be associated with a decline in end-tidal CO2 tension (r = 0.84), whereas VA BF appears to be affected by a change in cardiac output (r = 0.87). In addition, a change in ECA BF during Heat was negatively correlated with a change in ICA BF (r = -0.75). Heat stress resulted in modification of the vascular response of head and brain arteries to exercise, which resulted in an alteration in the distribution of cardiac output. Moreover, a hyperthermia-induced increase in extracranial BF might compromise anterior CBF during exercise with heat stress. PMID- 26846549 TI - SERCA2a upregulation ameliorates cellular alternans induced by metabolic inhibition. AB - Cardiac alternans has been associated with the incidence of ventricular tachyarrhythmias and sudden cardiac death. The aim of this study was to investigate the effect of impaired mitochondrial function in the genesis of cellular alternans and to examine whether modulating the sarcoplasmic reticulum (SR) Ca(2+)ameliorates the level of alternans. Cardiomyocytes isolated from control and doxycyline-induced sarco(endo)plasmic reticulum Ca(2+)-ATPase 2a (SERCA2a)-upregulated mice were loaded with two different Ca(2+)indicators to selectively measure mitochondrial and cytosolic Ca(2+)using a custom-made fluorescence photometry system. The degree of alternans was defined as the alternans ratio (AR) [1 - (small Ca(2+)intensity)/(large Ca(2+)intensity)]. Blocking of complex I and II, cytochrome-coxidase, F0F1synthase, alpha ketoglutarate dehydrogenase of the electron transport chain, increased alternans in both control and SERCA2a mice (P< 0.01). Changes in AR in SERCA2a-upregulated mice were significantly less pronounced than those observed in control in seven of nine tested conditions (P< 0.04).N-acetyl-l-cysteine (NAC), rescued alternans in myocytes that were previously exposed to an oxidizing agent (P< 0.001). CGP, an antagonist of the mitochondrial Na(+)-Ca(2+)exchanger, had the most severe effect on AR. Exposure to cyclosporin A, a blocker of the mitochondrial permeability transition pore reduced CGP-induced alternans (P< 0.0001). The major findings of this study are that impairment of mitochondrial Ca(2+)cycling and energy production leads to a higher amplitude of alternans in both control and SERCA2a-upregulated mice, but changes in SERCA2a-upregulated mice are less severe, indicating that SERCA2a mice are more capable of sustaining electrical stability during stress. This suggests a relationship between sarcoplasmic Ca(2+)content and mitochondrial dysfunction during alternans, which may potentially help to understand changes in Ca(2+)signaling in myocytes from diseased hearts, leading to new therapeutic targets. PMID- 26846550 TI - A standard, single dose of inhaled terbutaline attenuates hyperpnea-induced bronchoconstriction and mast cell activation in athletes. AB - Release of bronchoactive mediators from mast cells during exercise hyperpnea is a key factor in the pathophysiology of exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effect of a standard, single dose of an inhaled beta2-adrenoceptor agonist on mast cell activation in response to dry air hyperpnea in athletes with EIB. Twenty-seven athletes with EIB completed a randomized, double-blind, placebo-controlled, crossover study. Terbutaline (0.5 mg) or placebo was inhaled 15 min prior to 8 min of eucapnic voluntary hyperpnea (EVH) with dry air. Pre- and postbronchial challenge, urine samples were analyzed by enzyme immunoassay for 11beta-prostaglandin F2alpha (11beta-PGF2alpha). The maximum fall in forced expiratory volume in 1 s of 14 (12-20)% (median and interquartile range) following placebo was attenuated to 7 (5-9)% with the administration of terbutaline (P < 0.001). EVH caused a significant increase in 11beta-PGF2alpha from 41 (27-57) ng/mmol creatinine at baseline to 58 (43-72) ng/mmol creatinine at its peak post-EVH following placebo (P = 0.002). The rise in 11beta-PGF2alpha was inhibited with administration of terbutaline: 39 (28-44) ng/mmol creatinine at baseline vs. 40 (33-58) ng/mmol creatinine at its peak post EVH (P = 0.118). These data provide novel in vivo evidence of mast cell stabilization following inhalation of a standard dose of terbutaline prior to bronchial provocation with EVH in athletes with EIB. PMID- 26846551 TI - Mechanisms of airway responses to esophageal acidification in cats. AB - Acid in the esophagus causes airway constriction, tracheobronchial mucous secretion, and a decrease in tracheal mucociliary transport rate. This study was designed to investigate the neuropharmacological mechanisms controlling these responses. In chloralose-anesthetized cats (n = 72), we investigated the effects of vagotomy or atropine (100 MUg.kg(-1).30 min(-1) iv) on airway responses to esophageal infusion of 0.1 M PBS or 0.1 N HCl at 1 ml/min. We quantified 1) diameter of the bronchi, 2) tracheobronchial mucociliary transport rate, 3) tracheobronchial mucous secretion, and 4) mucous content of the tracheal epithelium and submucosa. We found that vagotomy or atropine blocked the airway constriction response but only atropine blocked the increase in mucous output and decrease in mucociliary transport rate caused by esophageal acidification. The mucous cells of the mucosa produced more Alcian blue- than periodic acid-Schiff (PAS)-stained mucosubstances, and the mucous cells of the submucosa produced more PAS- than Alcian blue-stained mucosubstances. Selective perfusion of the different segments of esophagus with HCl or PBS resulted in significantly greater production of PAS-stained mucus in the submucosa of the trachea adjacent to the HCl-perfused esophagus than in that adjacent to the PBS-perfused esophagus. In conclusion, airway constriction caused by esophageal acidification is mediated by a vagal cholinergic pathway, and the tracheobronchial transport response is mediated by cholinergic receptors. Acid perfusion of the esophagus selectively increases production of neutral mucosubstances of the apocrine glands by a local mechanism. We hypothesize that the airway responses to esophageal acid exposure are part of the innate, rather than acute emergency, airway defense system. PMID- 26846554 TI - Effects of isolation and confinement on humans-implications for manned space explorations. AB - Human psychology and physiology are significantly altered by isolation and confinement. In light of planned exploration class interplanetary missions, the related adverse effects on the human body need to be explored and defined as they have a large impact on a mission's success. Terrestrial space analogs offer an excellent controlled environment to study some of these stressors during a space mission in isolation without the complex environment of the International Space Station. Participants subjected to these space analog conditions can encounter typical symptoms ranging from neurocognitive changes, fatigue, misaligned circadian rhythm, sleep disorders, altered stress hormone levels, and immune modulatory changes. This review focuses on both the psychological and the physiological responses observed in participants of long-duration spaceflight analog studies, such as Mars500 or Antarctic winter-over. They provide important insight into similarities and differences encountered in each simulated setting. The identification of adverse effects from confinement allows not only the crew to better prepare for but also to design feasible countermeasures that will help support space travelers during exploration class missions in the future. PMID- 26846553 TI - Fatigue-induced adjustment in antagonist coactivation by old adults during a steadiness task. AB - The purpose of this study was to determine the adjustments in the level of coactivation during a steadiness task performed by young and old adults after the torque-generating capacity of the antagonist muscles was reduced by a fatiguing contraction. Torque steadiness (coefficient of variation) and electromyographic activity of the extensor and flexor carpi radialis muscles were measured as participants matched a wrist extensor target torque (10% maximum) before and after sustaining an isometric contraction (30% maximum) with wrist flexors to task failure. Time to failure was similar (P = 0.631) for young (417 +/- 121 s) and old (452 +/- 174 s) adults. The reduction in maximal voluntary contraction torque (%initial) for the wrist flexors after the fatiguing contraction was greater (P = 0.006) for young (32.5 +/- 13.7%) than old (21.8 +/- 6.6%) adults. Moreover, maximal voluntary contraction torque for the wrist extensors declined for old (-13.7 +/- 12.7%; P = 0.030), but not young (-5.4 +/- 13.8%; P = 0.167), adults. Torque steadiness during the matching task with the wrist extensors was similar before and after the fatiguing contraction for both groups, but the level of coactivation increased after the fatiguing contraction for old (P = 0.049) but not young (P = 0.137) adults and was twice the amplitude for old adults (P = 0.002). These data reveal that old adults are able to adjust the amount of antagonist muscle activity independent of the agonist muscle during steady submaximal contractions. PMID- 26846555 TI - Motor control of landing from a countermovement jump in simulated microgravity. AB - Landing from a jump implies proper positioning of the lower limb segments and the generation of an adequate muscular force to cope with the imminent collision with the ground. This study assesses how a hypogravitational environment affects the control of landing after a countermovement jump (CMJ). Eight participants performed submaximal CMJs on Earth (1-g condition) and in a weightlessness environment with simulated gravity conditions generated by a pull-down force (1-, 0.6-, 0.4-, and 0.2-g0 conditions). External forces applied to the body, movements of the lower limb segments, and muscular activity of six lower limb muscles were recorded. 1) All subjects were able to jump and stabilize their landing in all experimental conditions, except one subject in 0.2-g0 condition. 2) The mechanical behavior of lower limb muscles switches during landing from a stiff spring to a compliant spring associated with a damper. This is true whatever the environment, on Earth as well as in environments where sensory inputs are altered. 3) The motor control of landing in simulated 1 g0 reveals an increased "safety margin" strategy, illustrated by increased stiffness and damping coefficient compared with landing on Earth. 4) The motor command is adjusted to the task constraints: muscular activity of lower limb extensors and flexors, stiffness and damping coefficient decrease according to the decreased gravity level. Our results show that even if in daily living gravity can be perceived as a constant factor, subjects can cope with altered sensory signals, taking advantage of the remaining information (visual and/or decreased proprioceptive inputs). PMID- 26846552 TI - Pharmacological targeting of mitochondrial reactive oxygen species counteracts diaphragm weakness in chronic heart failure. AB - Diaphragm muscle weakness in chronic heart failure (CHF) is caused by elevated oxidants and exacerbates breathing abnormalities, exercise intolerance, and dyspnea. However, the specific source of oxidants that cause diaphragm weakness is unknown. We examined whether mitochondrial reactive oxygen species (ROS) cause diaphragm weakness in CHF by testing the hypothesis that CHF animals treated with a mitochondria-targeted antioxidant have normal diaphragm function. Rats underwent CHF or sham surgery. Eight weeks after surgeries, we administered a mitochondrial-targeted antioxidant (MitoTEMPO; 1 mg.kg(-1).day(-1)) or sterile saline (Vehicle). Left ventricular dysfunction (echocardiography) pre- and posttreatment and morphological abnormalities were consistent with the presence of CHF. CHF elicited a threefold (P < 0.05) increase in diaphragm mitochondrial H2O2 emission, decreased diaphragm glutathione content by 23%, and also depressed twitch and maximal tetanic force by ~20% in Vehicle-treated animals compared with Sham (P < 0.05 for all comparisons). Diaphragm mitochondrial H2O2 emission, glutathione content, and twitch and maximal tetanic force were normal in CHF animals receiving MitoTEMPO. Neither CHF nor MitoTEMPO altered the diaphragm protein levels of antioxidant enzymes: superoxide dismutases (CuZn-SOD or MnSOD), glutathione peroxidase, and catalase. In both Vehicle and MitoTEMPO groups, CHF elicited a ~30% increase in cytochrome c oxidase activity, whereas there were no changes in citrate synthase activity. Our data suggest that elevated mitochondrial H2O2 emission causes diaphragm weakness in CHF. Moreover, changes in protein levels of antioxidant enzymes or mitochondrial content do not seem to mediate the increase in mitochondria H2O2 emission in CHF and protective effects of MitoTEMPO. PMID- 26846556 TI - Barometric calibration of a luminescent oxygen probe. AB - The invention of the phosphorescence quenching method for the measurement of oxygen concentration in blood and tissue revolutionized physiological studies of oxygen transport in living organisms. Since the pioneering publication by Vanderkooi and Wilson in 1987, many researchers have contributed to the measurement of oxygen in the microcirculation, to oxygen imaging in tissues and microvessels, and to the development of new extracellular and intracellular phosphorescent probes. However, there is a problem of congruency in data from different laboratories, because of interlaboratory variability of the calibration coefficients in the Stern-Volmer equation. Published calibrations for a common oxygen probe, Pd-porphyrin + bovine serum albumin (BSA), vary because of differences in the techniques used. These methods are used for the formation of oxygen standards: chemical titration, calibrated gas mixtures, and an oxygen electrode. Each method in turn also needs calibration. We have designed a barometric method for the calibration of oxygen probes by using a regulated vacuum to set multiple PO2 standards. The method is fast and accurate and can be applied to biological fluids obtained during or after an experiment. Calibration over the full physiological PO2 range (1-120 mmHg) takes ~15 min and requires 1-2 mg of probe. PMID- 26846557 TI - Unilateral lower limb suspension: From subject selection to "omic" responses. AB - The unilateral lower limb suspension (ULLS) method was developed, introduced, and validated in the quest for a simple, effective, and highly reliable human analog to study the consequences of spaceflight on muscle size and function. Because withdrawal of weight bearing for no more than 2-3 days is sufficient to inflict disturbances in protein metabolism of postural muscles, it is imperative ULLS serves as a very powerful method to manifest skeletal muscle adaptations similar to those experienced in 0 g. Thus the rate of global muscle loss appears rather constant over the first 2 mo, amounting to about 2-3% per week. At the microscopic level, these changes are accompanied by a corresponding decrease in individual muscle fiber size. ULLS alters metabolism favoring more carbohydrate over fat substrate utilization. Altogether, these changes result in impaired work and endurance capacity of muscles being subjected to ULLS. Maximal voluntary force decreases out of proportion to the muscle loss, suggesting motor control is modified. Past reviews offer near exhaustive information on ULLS-induced responses with regard to the above changes. Hence, the current brief review describes more broadly the evolution of the ULLS model, from issues of subject recruitment and compliance control, to recent advances unraveling molecular mechanisms facilitating unloading-induced muscle wasting. Such knowledge is critical in designing future studies aimed at exploring and developing exercise countermeasures or other means to combat the debilitating effects on muscle experienced by astronauts during long-haul missions in Orbit. PMID- 26846558 TI - Between-day test-retest reliability of gait variability in older individuals improves with a familiarization trial. AB - Gait variability is an important measure in clinical settings to diagnose older individuals with fall risk. This study examines whether a familiarization trial improves test-retest reliability of gait variability. Twenty-two older participants walked twice at 1 day and twice 7 days later. The standard deviations of stride length, swing time, stance time, stride time and minimum foot clearance were calculated. The test-retest reliability of (1) between-day comparison of the first trials and (2) between-day comparison of the second trials of all gait variability measures was quantified with the intraclass correlation coefficient (ICC), the smallest detectable differences (SDD) and the bias and the limits of agreement (LoA). The between-day comparison of the second trials per day showed higher ICC values, lower LoA values and lower SDD values in all analyzed parameters. Our data suggest that the reliability of gait variability in an older population can be considerably improved just with the aid of one familiarization trial. PMID- 26846559 TI - Relationship between the polymorphism in exon 5 of BACE1 gene and Alzheimer's disease. AB - BACKGROUND AND AIMS: The beta-Site APP-cleaving enzyme 1 (BACE1) gene polymorphism (rs638405) has been extensively investigated for association to Alzheimer's disease (AD). However, results of different studies have been contradictory. The aim of this meta-analysis was to evaluate the association between BACE1 gene polymorphism (rs638405) and AD. METHODS: All eligible studies were searched in PubMed, Cochrane Library, Embase, SinoMed, and the China Knowledge Resource Integrated Database. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) were used to evaluate the strength of the association between BACE1 gene polymorphism and AD. RESULTS: Twenty studies in 19 papers containing 4377 AD patients and 4563 controls were included for rs638405 polymorphism. The results suggested that rs638405 in BACE1 was not associated with the risk of AD. Stratification analyses indicated rs638405 decreased the risk of apolipoprotein-E epsilon4 (APOE4) positive AD patients. Furthermore, we found rs638405 also decreased the risk of Asian AD patients. By exclusion of three studies that did not conform to Hardy-Weinberg equilibrium (HWE), our data suggested rs638405 in BACE1 was a protective factor of AD. CONCLUSIONS: To sum up, our data indicated that BACE1 gene polymorphism in exon 5 might decrease the risk of Asian AD and APOE4 positive patients. PMID- 26846560 TI - How did you choose a mode of birth? Experiences of nulliparous women from Turkey. AB - BACKGROUND: One of the most important decisions that women have to make after becoming pregnant concerns their mode of birth, and these decisions are influenced by complex physiological, psychological and socio-cultural factors. AIM: To obtain in-depth descriptions of nulliparous women's experiences during the decision-making process for their mode of birth and to reveal their beliefs, attitudes and values. METHODS: This is a qualitative, phenomenological study that included 29 nulliparous women. Data were collected using semi-structured, face-to face interviews and analysed using the constant comparison method and guidelines developed by Collaizi. FINDINGS: The women's experiences during their decision making process for their mode of birth were placed into one of four categories, "getting confused", "no matter what happens", "others influencing women's decisions" and "make a decision one way or the other". Vaginal births were considered under the theme "natural but hard way" and caesarean sections under the theme "easy choice". The women indicated that they wanted to have vaginal births, but that they were not offered knowledge and support about modes of birth from health care professionals and, as a result, they asked their relatives for support. CONCLUSION: It is important to obtain pregnant women's preferences for modes of birth so that knowledge, support and care can be provided and so that they can be involved in the decision-making process. Therefore, health care professionals should understand pregnant women's experiences during the decision making process for their mode of birth. PMID- 26846561 TI - Visualising inter-subject variability in fMRI using threshold-weighted overlap maps. AB - Functional neuroimaging studies are revealing the neural systems sustaining many sensory, motor and cognitive abilities. A proper understanding of these systems requires an appreciation of the degree to which they vary across subjects. Some sources of inter-subject variability might be easy to measure (demographics, behavioural scores, or experimental factors), while others are more difficult (cognitive strategies, learning effects, and other hidden sources). Here, we introduce a simple way of visualising whole-brain consistency and variability in brain responses across subjects using threshold-weighted voxel-based overlap maps. The output quantifies the proportion of subjects activating a particular voxel or region over a wide range of statistical thresholds. The sensitivity of our approach was assessed in 30 healthy adults performing a matching task with their dominant hand. We show how overlap maps revealed many effects that were only present in a subsample of our group; we discuss how overlap maps can provide information that may be missed or misrepresented by standard group analysis, and how this information can help users to understand their data. In particular, we emphasize that functional overlap maps can be particularly useful when it comes to explaining typical (or atypical) compensatory mechanisms used by patients following brain damage. PMID- 26846563 TI - Short and long-term outcome following surgical stabilization of tarsocrural instability in dogs. AB - OBJECTIVES: To evaluate the outcome and complications following surgical stabilization of canine tarsocrural luxations. METHODS: Medical records of dogs which were surgically treated for tarsocrural joint instability between February 2007 and June 2014 were reviewed. Surgical technique, complications and long-term outcome (via questionnaire and Canine Brief Pain Inventory) were assessed. RESULTS: Twenty-four dogs (26 joints) were included. All injuries were traumatic. All joints had associated fractures; malleolar in 21/26 limbs (13/26 medial). Eight joints had internal fracture fixation and transarticular external skeletal fixator, six had external fixator alone, four had prosthetic ligaments with external fixator, and four had prosthetic ligaments with external coaptation. Two joints had pantarsal arthrodesis and two primary ligament repair. Complications occurred in 24/26 limbs giving 45 distinct complications; 16 were minor, 29 major, and 31 complications were external fixator associated. Prosthetic ligaments were significantly associated with major complications (p = 0.017); five out of eight required subsequent removal between 105-1006 days. Cost was significantly associated with major complications (p = 0.017) and soft tissue wounds (p = 0.03). Long-term lameness was seen in nine of 14 dogs. There was no association between pain severity (p = 0.3) and pain interference scores (p = 0.198) when comparing stabilization methods. CLINICAL SIGNIFICANCE: Complications are common; however many are external fixator related. Prosthetic ligaments are significantly associated with major complications. Regardless of technique, a degree of ongoing lameness is likely. PMID- 26846562 TI - Later emergence of acquired drug resistance and its effect on treatment outcome in patients treated with Standard Short-Course Chemotherapy for tuberculosis. AB - BACKGROUNDS: The failure of current Standard Short-Course Chemotherapy (SCC) in new and previously treated cases with tuberculosis (TB) was mainly due to drug resistance development. But little is known on the characteristics of acquired drug resistant TB during SCC and its correlation with SCC failure. The objective of the study is to explore the traits of acquired drug resistant TB emergence and evaluate their impacts on treatment outcomes. METHODS: A prospective observational study was performed on newly admitted smear positive pulmonary TB (PTB) cases without drug resistance pretreatment treated with SCC under China's National TB Control Program (NTP) condition from 2008 to 2010. Enrolled cases were followed up through sputum smear, culture and drug susceptibility testing (DST) at the end of 1, 2, and 5 months after treatment initiation. The effect factors of early or late emergence of acquired drug resistant TB , such as acquired drug resistance patterns, the number of acquired resistant drugs and previous treatment history were investigated by multivariate logistic regression; and the impact of acquired drug resistant TB emergence on treatment failure were further evaluated. RESULTS: Among 1671 enrolled new and previously treated cases with SCC, 62 (3.7%) acquired different patterns of drug resistant TB at early period within 2 months or later around 3-5 months of treatment. Previously treated cases were more likely to develop acquired multi-drug resistant TB (MDR TB) (OR, 3.8; 95%CI, 1.4-10.4; P = 0.015). Additionally, acquired MDR-TB cases were more likely to emerge at later period around 3-5 months after treatment starting than that of non-MDR-TB mainly appeared within 2 months (OR, 8.3; 95%CI, 1.7-39.9; P = 0.008). Treatment failure was associated with late acquired drug resistant TB emergence (OR, 25.7; 95%CI, 4.3-153.4; P < 0.001) with the reference of early acquired drug resistant TB emergence. CONCLUSIONS: This study demonstrates that later development of acquired drug resistant TB during SCC is liable to suffer treatment failure and acquired MDR-TB pattern may be one of the possible causes. PMID- 26846564 TI - Traditional knowledge and its transmission of wild edibles used by the Naxi in Baidi Village, northwest Yunnan province. AB - BACKGROUND: The collection and consumption of wild edibles is an important part in livelihood strategies throughout the world. There is an urgent need to document and safeguard the wild food knowledge, especially in remote areas. The aims of this study are to accomplish detailed investigation of wild edibles used by the Naxi in Baidi village and evaluate them to identify innovative organic food products. Also, we aim to explore the characteristics of distribution and transmission of the traditional knowledge (TK) on wild edibles among the Naxi. METHODS: Data was collected through a semi-structured interview of key informants above the age of 20 years, chosen carefully by a snowball sampling. The interviews were supplemented by free lists and participatory observation methods. Informants below 20 years were interviewed to test their knowledge of traditional practices. A quantitative index like Cultural Importance Index (CI) was used to evaluate the relative importance of the different wild edibles. Linear regression and t-test were performed to test variation in the TK among the informants of different age groups and genders. RESULTS: Altogether 173 wild edible plant species belonging to 76 families and 139 genera were recorded in the study. Cardamine macrophylla, C. tangutorum and Eutrema yunnanense, have traditionally been consumed as an important supplement to the diet, particularly during food shortages as wild vegetables. The age was found to have a significant effect on TK, but there was no significant difference between male and female informant in knowledge abundance. The traditional food knowledge was dynamic and affected by social factors. Also, it was descending partly among younger generations in Baidi. CONCLUSION: Baidi village is a prime example of a rapidly changing community where local traditions compete with modern ways of life. Overall, this study provides a deeper understanding of the Naxi peoples' knowledge on wild edibles. Some wild edibles might have an interesting dietary constituent, which need in-depth studies. Such detail studies can help to promote the market in one hand and protect TK in the other. Protecting TK from disappearing in succeeding generations is necessary, and understanding the dynamics of TK is one important solution to this dilemma. PMID- 26846565 TI - Branched-chain and aromatic amino acid profiles and diabetes risk in Chinese populations. AB - Recent studies revealed strong evidence that branched-chain and aromatic amino acids (BCAAs and AAAs) are closely associated with the risk of developing type 2 diabetes in several Western countries. The aim of this study was to evaluate the potential role of BCAAs and AAAs in predicting the diabetes development in Chinese populations. The serum levels of valine, leucine, isoleucine, tyrosine, and phenylalanine were measured in a longitudinal and a cross sectional studies with a total of 429 Chinese participants at different stages of diabetes development, using an ultra-performance liquid chromatography triple quadruple mass spectrometry platform. The alterations of the five AAs in Chinese populations are well in accordance with previous reports. Early elevation of the five AAs and their combined score was closely associated with future development of diabetes, suggesting an important role of these metabolites as early markers of diabetes. On the other hand, the five AAs were not as good as existing clinical markers in differentiating diabetic patients from their healthy counterparts. Our findings verified the close correlation of BCAAs and AAAs with insulin resistance and future development of diabetes in Chinese populations and highlighted the predictive value of these markers for future development of diabetes. PMID- 26846567 TI - Long-Term Prevalence and Demographic Trends in U.S. Adolescent Inhalant Use: Implications for Clinicians and Prevention Scientists. AB - BACKGROUND: Inhalant use by adolescents is cause for concern due to the early age of inhalant use initiation and the many short- and long-term health consequences that can occur concurrently with and subsequent to use. However, inhalant use research has been limited relative to the literature available on other drug use. OBJECTIVES: The present research examined long-term trends in inhalant use prevalence, demographic risk factors of inhalant use, and median grade level of first use. METHODS: Monitoring the Future data from 1991 to 2011, which includes information drawn from United States eighth, tenth, and twelfth graders, were examined. The total sample comprised more than one million participants. Results were examined descriptively with figures and quantitatively with mixed-effects regression models of the effect of time on use rates. RESULTS: Inhalant use prevalence rates generally declined over the selected period. Though rates of use by males and females decreased significantly, the proportion of females among lifetime users increased significantly. Whites, Hispanics, and members of uncategorized "other" ethnicities showed the highest prevalence rates. Although the proportion of Whites among lifetime users decreased significantly, the proportion of Hispanics and "other" ethnicities increased significantly. The median first use was between sixth and ninth grade. CONCLUSIONS/IMPORTANCE: Results suggest a need to tailor inhalant use treatment and prevention programs to the needs of specific demographic groups and to target interventions early to prevent youth inhalant use. Strengths, limitations, and directions for future research are discussed. PMID- 26846566 TI - Targeting of cancer-associated fibroblasts enhances the efficacy of cancer chemotherapy by regulating the tumor microenvironment. AB - Cancer-associated fibroblasts (CAFs), key components of the tumor stroma, can regulate tumorigenesis by altering the tumor microenvironment in variety of ways to promote angiogenesis, recruit inflammatory immune cells and remodel the extracellular matrix. Using a murine xenograft model of colon carcinoma, the present study observed that oxaliplatin increased the accumulation of CAFs and stimulated the production of cytokines associated with CAFs. When oxaliplatin was combined with the small-molecule dipeptidyl peptidase inhibitor PT-100, which inhibits CAFs by targeting fibroblast activation protein (FAP), the accumulation of CAFs was markedly reduced, xenograft tumor growth was significantly suppressed and the survival of the mice increased, compared to those of mice treated with oxaliplatin or PT-100 alone. Furthermore, the xenograft tumor tissues of mice treated with oxaliplatin and PT-100 contained lower numbers of tumor-associated macrophages and dendritic cells, expressed lower levels of cytokines associated with CAFs and had a lower density of CD31+ endothelial cells. The present study demonstrated that pharmacological inhibition of CAFs improved the response to chemotherapy, reduced the recruitment of immune tumor-promoting cells and inhibited angiogenesis. Combining chemotherapy with agents which target CAFs may represent a novel strategy for improving the efficacy of chemotherapy and reducing chemoresistance. PMID- 26846569 TI - Bryant and Stabler Signs in a Preterm Infant. PMID- 26846568 TI - Cytokine expression in the visceral adipose tissue after laparoscopic and conventional surgery in a rodent model. AB - BACKGROUND: Laparoscopic Surgery has become a worldwide standard procedure for a variety of indications. This has been attributed to a milder postoperative inflammatory response by the innate immune system potentially mediated through immune mediators released by the visceral adipose tissue (VAT). However, an in vivo experimental evidence is lacking and is the issue of our present study. METHODS: Male Wistar rats (N = 24) underwent standardized surgical procedures of conventional cecum resection (CCR), conventional sham operation, laparoscopic cecum resection (LCR), or laparoscopic sham operation. Cytokine expression of leptin, resistin, and IL-6 was analyzed in VAT before and after resection by quantitative RT-PCR. RESULTS: Postoperative leptin gene expression was reduced in the CCR and LCR groups, while expression was not significantly affected in both sham groups compared to the preoperative levels. In contrast, IL-6 expression was not affected in the LCR group, but was significantly elevated in the CCR cohort. The IL-6 expression was significantly higher in CCR compared to LCR. Resistin expression levels did not differ between all groups. CONCLUSIONS: Our study underlines the role of immunological involvement of VAT in the postoperative phase. Low leptin levels seem to act as a stimulator for energy uptake in order to cope with postoperative stress. A lower IL-6 expression in the LCR compared to the CCR group may indicate a weaker inflammatory activity potentially adding to the clinical benefits observed in patients undergoing LS. PMID- 26846570 TI - Comorbidity of Atopic Disorders with Autism Spectrum Disorder and Attention Deficit/Hyperactivity Disorder. AB - OBJECTIVE: To assess the relationship between allergic manifestations in early life and the occurrence of newly diagnosed autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) throughout childhood. STUDY DESIGN: We collected a population-based longitudinal cohort comprising children enrolled in Taiwan's National Health Insurance Program during 2000-2010. We first identified 387,262 children who had a diagnosis of atopic dermatitis (AD) before age 2 years, with 1:1 individualized matching to children without AD. Cox regression analyses were performed to estimate the early-onset and cumulative effects of allergic manifestations on ASD and ADHD. RESULTS: An estimated 0.5% of AD-exposed children received a diagnosis of ASD, and 3.7% were diagnosed with ADHD, significantly higher than the respective rates of 0.4% and 2.9% found in their nonexposed peers. Having AD before age 2 years was associated with an increased hazard ratio (HR) for ASD by 10% and that for ADHD by 16%; such increases were particularly prominent among those with earlier-onset or more severe AD. HRs were especially higher for children with persistent AD and emerging atopic respiratory diseases in childhood (eg, for ASD, adjusted HR, 1.75 and 2.13, respectively; P < .001). CONCLUSION: The observed increased risks of ASD and ADHD associated with AD in infancy suggest that a disordered immunologic response may exert effects on neurodevelopment and have implications for research into etiology and treatment strategies. PMID- 26846571 TI - Knowledge about Human Papillomavirus and Time to Complete Vaccination among Vulnerable Female Youth. AB - OBJECTIVE: To examine the association of knowledge about human papillomavirus (HPV) on the time to completion of the 3-dose quadrivalent vaccine series in an inner-city population of adolescent female subjects at high risk for infection. STUDY DESIGN: We prospectively followed 139 female subjects aged 14-20 years enrolled in a vaccine surveillance study in New York City during a period of at least 24 months. Participants were given a 30-item true or false survey on HPV at enrollment and ranked according to the number of correct responses. Multivariate Cox regression was used to examine the association between level of knowledge about HPV and time to completion (in days) of vaccine dose 1-3, dose 1-2, and dose 2-3. RESULTS: Overall time to completion of the 3-dose vaccine ranged from 158 days to 1114 days. Participants in the high knowledge group (top quartile) were significantly more likely to complete the 3-dose series earlier (hazard ratio 1.69, 95% CI 1.03-2.77; P = .04), in particular doses 2-3 (hazard ratio 1.71, 95% CI 1.02-2.89; P = .04), than those with low-to-moderate knowledge (bottom 3 quartiles). CONCLUSIONS: These findings suggest that knowledge of HPV is associated with shorter time to complete the 3-dose HPV vaccine series. Educational campaigns at time of vaccination may be important to improve vaccine adherence. PMID- 26846572 TI - Universal Screening for Sexually Transmitted Infections among Asymptomatic Adolescents in an Urban Emergency Department: High Acceptance but Low Prevalence of Infection. AB - OBJECTIVES: To evaluate acceptance of sexually transmitted infection (STI) screening and measure STI prevalence in an asymptomatic adolescent emergency department (ED) population. STUDY DESIGN: This was a prospectively enrolled cross sectional study of 14- to 21-year-old patients who sought care at an urban pediatric ED with non-STI related complaints. Participants completed a computer assisted questionnaire to collect demographic and behavioral data and were asked to provide a urine sample to screen for Chlamydia trachomatis and Neisseria gonorrhoeae infection. We calculated STI screening acceptance and STI prevalence. We used logistic regression to identify factors associated with screening acceptance and presence of infection. RESULTS: Of 553 enrolled patients, 326 (59.0%) agreed to be screened for STIs. STI screening acceptability was associated with having public health insurance (aOR 1.7; 1.1, 2.5) and being sexually active (sexually active but denying high risk activity [aOR 1.7; 1.1, 2.5]; sexually active and reporting high risk activity [aOR 2.6; 1.5, 4.6]). Sixteen patients (4.9%; 95% CI 2.6, 7.3) had an asymptomatic STI. High-risk sexual behavior (aOR 7.2; 1.4, 37.7) and preferential use of the ED rather than primary care for acute medical needs (aOR 4.0; 1.3, 12.3) were associated with STI. CONCLUSIONS: STI screening is acceptable to adolescents in the ED, especially among those who declare sexual experience. Overall, there was a low prevalence of asymptomatic STI. Risk of STI was higher among youth engaging in high-risk sexual behavior and those relying on the ED for acute health care access. Targeted screening interventions may be more efficient than universal screening for STI detection in the ED. PMID- 26846573 TI - Study shows that Dry January does more good than harm. PMID- 26846574 TI - Treatment with novel AP-1 and NF-kappaB inhibitors restores the colonic endocrine cells to normal levels in rats with DSS-induced colitis. AB - The aim of this study was to determine the effects of two anti-inflammatory agents on the abnormalities in colonic endocrine cells in dextran sodium sulfate (DSS)-induced colitis. Colitis was induced in male Wistar rats (n=45) using DSS; a further 15 rats without colitis were included in a healthy control group. The animals with DSS-induced colitis were randomly divided into 3 treatment groups as follows: i) DSS group, rats were treated with 0.5 ml of 0.5% carboxymethyl cellulose (CMC); ii) DSS-G group, rats were treated with 3-[(dodecylthiocarbonyl) methyl]-glutarimide (DTCM-G), a novel activator protein 1 (AP-1) inhibitor, 20 mg/kg in CMC; and iii) DSS-Q group, rats were treated with dehydroxymethylepoxyquinomicin, a nuclear factor kappaB (NF-kappaB) inhibitor, 15 mg/kg in CMC. The treatments were administered intraperitoneally, twice daily for 5 days, after which the animals were sacrificed and tissue samples from the colon were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), enteroglucagon, pancreatic polypeptide (PP), somatostatin, leukocytes, B/T lymphocytes, B lymphocytes, T lymphocytes, macrophages/monocytes and mast cells. The densities of these endocrine and immune cells were quantified by computer aided image analysis. The densities of CgA-, serotonin-, PYY- and enteroglucagon producing cells were significantly higher, and those of PP- and somatostatin producing cells were significantly lower in the DSS-G, DSS-Q and control groups than in the DSS group. The densities of all the immune cells were lower in the DSS-G, DSS-Q and control groups than in the DSS group. The densities of all endocrine cell types and immune cells in both the DSS groups treated with anti inflammatory agents were restored to control levels. In conclusion, our data demonstrate that there is an interaction between endocrine and immune cells during inflammation. This interaction with subsequent changes in endocrine cells is responsible for the clinical manifestation of colitis symptoms. PMID- 26846575 TI - Dietary n-3 Fatty Acid, alpha-Tocopherol, Zinc, vitamin D, vitamin C, and beta carotene are Associated with Age-Related Macular Degeneration in Japan. AB - This case-control study reports the association between nutrient intake and neovascular age-related macular degeneration (AMD) in Japan. The nutrient intake of 161 neovascular AMD cases from two university hospitals and 369 population based control subjects from a cohort study was assessed using a brief-type self administered questionnaire on diet history, which required respondent recall of the usual intake of 58 foods during the preceding month. Energy-adjusted nutrient intake values were compared between the groups. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% CIs adjusted for smoking history, age, sex, chronic disease history, supplement use, and alcohol consumption. Logistic regression analysis demonstrated that low intakes of n-3 fatty acid, alpha tocopherol, zinc, vitamin D, vitamin C, and beta-carotene were associated with neovascular AMD (Trend P < 0.0001 for n-3 fatty acid, Trend P < 0.0001 for alpha tocopherol, Trend P < 0.0001 for zinc, Trend P = 0.002 for vitamin D, Trend P = 0.04 for vitamin C, Trend P = 0.0004 for beta-carotene). There was no association with retinol or cryptoxanthin intake and neovascular AMD (P = 0.67, 0.06). PMID- 26846576 TI - Initial Case Reports of Cancer in Naked Mole-rats (Heterocephalus glaber). AB - Naked mole-rats (NMRs;Heterocephalus glaber) are highly adapted, eusocial rodents renowned for their extreme longevity and resistance to cancer. Because cancer has not been formally described in this species, NMRs have been increasingly utilized as an animal model in aging and cancer research. We previously reported the occurrence of several age-related diseases, including putative pre-neoplastic lesions, in zoo-housed NMR colonies. Here, we report for the first time 2 cases of cancer in zoo-housed NMRs. In Case No. 1, we observed a subcutaneous mass in the axillary region of a 22-year-old male NMR, with histologic, immunohistochemical (pancytokeratin positive, rare p63 immunolabeling, and smooth muscle actin negative), and ultrastructural characteristics of an adenocarcinoma possibly of mammary or salivary origin. In Case No. 2, we observed a densely cellular, poorly demarcated gastric mass of polygonal cells arranged in nests with positive immunolabeling for synaptophysin and chromogranin indicative of a neuroendocrine carcinoma in an approximately 20-year-old male NMR. We also include a brief discussion of other proliferative growths and pre-cancerous lesions diagnosed in 1 zoo colony. Although these case reports do not alter the longstanding observation of cancer resistance, they do raise questions about the scope of cancer resistance and the interpretation of biomedical studies in this model. These reports also highlight the benefit of long-term disease investigations in zoo-housed populations to better understand naturally occurring disease processes in species used as models in biomedical research. PMID- 26846577 TI - The hypoxia-mimetic agent CoCl2 induces chemotherapy resistance in LOVO colorectal cancer cells. AB - Hypoxia, which is an important factor that mediates tumor progression and poor treatment response, is particularly associated with tumor chemoresistance. However, the molecular mechanisms underlying hypoxia-induced colorectal cancer chemoresistance remain unclear. The present study aimed to explore the mechanism underlying hypoxia-induced chemotherapy resistance in LOVO colorectal cancer cells. LOVO cells were cultured in a hypoxic environment simulated by cobalt chloride (CoCl2), which is a chemical inducer of hypoxia-inducible factor-1alpha (HIF-1alpha). HIF-1alpha is a transcription factor that has an important role in tumor cell adaptation to hypoxia, and controls the expression of several genes. Various CoCl2 concentrations are often used to simulate degrees of hypoxia. In the present study, following treatment with CoCl2, an MTT assay was conducted to determine the growth and drug sensitivity of LOVO cells. Reverse transcription polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels of HIF-1alpha and factors associated with chemotherapy resistance, including multidrug resistance protein (MRP) and multidrug resistant 1 (MDR1), which encodes the major transmembrane efflux transporter P-glycoprotein (P-gp). In addition, the expression levels of apoptosis-related proteins, including B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and Bcl-2 associated agonist of cell death (Bad) were detected by western blotting. Flow cytometry (FCM) was used to visually observe Adriamycin (ADR) accumulation and retention, thus analyzing intracellular drug transportation in cells under hypoxic and normoxic conditions. CoCl2-simulated hypoxia was able to inhibit tumor cell proliferation, and upregulate the expression levels of HIF-1alpha, MDR1/P-gp and MRP. In addition, proapoptotic members of the Bcl-2 protein family, Bax and Bad, were downregulated. The anti-apoptotic member Bcl-2 exhibited no significant change in expression, whereas the ratio of Bcl-2/Bax was increased. Results of FCM demonstrated that the intracellular retention of ADR was significantly decreased in the hypoxia group cells. In conclusion, the present study revealed that a CoCl2-simulated hypoxic microenvironment was able to effectively induce chemoresistance and reduce apoptosis in LOVO cells. PMID- 26846580 TI - Molecular mechanisms associated with 46,XX disorders of sex development. AB - In the female gonad, distinct signalling pathways activate ovarian differentiation while repressing the formation of testes. Human disorders of sex development (DSDs), such as 46,XX DSDs, can arise when this signalling is aberrant. Here we review the current understanding of the genetic mechanisms that control gonadal development, with particular emphasis on those that drive or inhibit ovarian differentiation. We discuss how disruption to these molecular pathways can lead to 46,XX disorders of ovarian development. Finally, we look at recently characterized novel genes and pathways that contribute and speculate how advances in technology will aid in further characterization of normal and disrupted human ovarian development. PMID- 26846581 TI - P2Y12 receptor inhibition and LPS-induced coagulation. AB - Platelets play a major role in the complex interactions involved in blood coagulation via multiple mechanisms. As reported in this issue, Schoergenhofer et al. tested the hypothesis that platelet inhibition by prasugrel, a potent platelet P2Y12 ADP receptor antagonist, attenuates the effect of lipopolysaccharide (LPS) on the blood coagulation system in healthy human subjects. LPS, a bacterial product with potent pro-inflammatory and pro thrombotic effects, plays a central role in sepsis. It activates monocytes and endothelial cells via Toll-like receptor (TLR) 4 and other TLRs to stimulate production of TF and other pro-coagulant molecules, chemokines and cytokines. Treatment with prasugrel did not decrease biomarkers of coagulaion. A better understanding of the relative roles of platelet and coagulation mechanisms in triggering the pro-thrombotic state may lead to more effective antithrombotic strategies. PMID- 26846578 TI - Mitochondrial cytochrome c oxidase deficiency. AB - As with other mitochondrial respiratory chain components, marked clinical and genetic heterogeneity is observed in patients with a cytochrome c oxidase deficiency. This constitutes a considerable diagnostic challenge and raises a number of puzzling questions. So far, pathological mutations have been reported in more than 30 genes, in both mitochondrial and nuclear DNA, affecting either structural subunits of the enzyme or proteins involved in its biogenesis. In this review, we discuss the possible causes of the discrepancy between the spectacular advances made in the identification of the molecular bases of cytochrome oxidase deficiency and the lack of any efficient treatment in diseases resulting from such deficiencies. This brings back many unsolved questions related to the frequent delay of clinical manifestation, variable course and severity, and tissue-involvement often associated with these diseases. In this context, we stress the importance of studying different models of these diseases, but also discuss the limitations encountered in most available disease models. In the future, with the possible exception of replacement therapy using genes, cells or organs, a better understanding of underlying mechanism(s) of these mitochondrial diseases is presumably required to develop efficient therapy. PMID- 26846582 TI - Chemoselective and stereoselective lithium carbenoid mediated cyclopropanation of acyclic allylic alcohols. AB - The reaction of geraniol with different lithium carbenoids generated from n-BuLi and the corresponding dihaloalkane has been evaluated. The reaction occurs in a chemo and stereoselective manner, which is consistent with a directing effect from the oxygen of the allylic moiety. Furthermore, a set of polyenes containing allylic hydroxyl or ether groups were chemoselectively and stereoselectively converted into the corresponding gem-dimethylcyclopropanes in one single step in moderate to good yields mediated by a lithium carbenoid generated in situ by the reaction of n-BuLi and 2,2-dibromopropane. PMID- 26846583 TI - Erectile dysfunction in COPD: A hidden co-morbidity. PMID- 26846579 TI - The role of inflammation in the pathology of preeclampsia. AB - Preeclampsia (PE) affects 5-7% of all pregnancies in the United States and is the leading cause of maternal and prenatal morbidity. PE is associated with hypertension after week 20 of gestation, decreased renal function and small-for gestational-age babies. Women with PE exhibit chronic inflammation and production of autoantibodies. It is hypothesized that during PE, placental ischaemia occurs as a result of shallow trophoblast invasion which is associated with an immune imbalance where pro-inflammatory CD4(+) T-cells are increased and T regulatory cells (Tregs) are decreased. This imbalance leads to chronic inflammation characterized by oxidative stress, pro-inflammatory cytokines and autoantibodies. Studies conducted in our laboratory have demonstrated the importance of this immune imbalance in causing hypertension in response to placental ischaemia in pregnant rats. These studies confirm that increased CD4(+) T-cells and decreased Tregs during pregnancy leads to elevated inflammatory cytokines, endothelin (ET 1), reactive oxygen species (ROS) and agonistic autoantibodies to the angiotensin II (Ang II), type 1 receptor (AT1-AA). All of these factors taken together play an important role in increasing the blood pressure during pregnancy. Specifically, this review focuses on the decrease in Tregs, and their associated regulatory cytokine interleukin (IL)-10, which is seen in response to placental ischaemia during pregnancy. This study will also examine the effect of regulatory immune cell repopulation on the pathophysiology of PE. These studies show that restoring the balance of the immune system through increasing Tregs, either by adoptive transfer or by infusing IL-10, reduces the blood pressure and pathophysiology associated with placental ischaemia in pregnant rats. PMID- 26846586 TI - A non-chemically selective top-down approach towards the preparation of hierarchical TS-1 zeolites with improved oxidative desulfurization catalytic performance. AB - Hierarchical TS-1 zeolites with secondary macropores have been successfully prepared by using two different fluoride-containing chemical etching post-treated routes. Hierarchical TS-1 zeolites exhibited a chemical composition similar to that of the parent material and showed remarkably enhanced catalytic activity in oxidative desulfurization reaction. PMID- 26846584 TI - Preclinical lung disease in early rheumatoid arthritis. AB - Early detection and treatment of lung disease in patients with rheumatoid arthritis (RA) may ameliorate disease progression. The objectives of this study were to investigate the frequency of asymptomatic lung abnormalities in early RA patients and the potential association of positive RA blood reactive biomolecules with lung involvement. A prospective observational study was performed in a cohort of patients with early RA (joint symptoms < 2 years) without respiratory symptoms, who were included in a screening program for lung disease with a baseline chest radiograph (CR) and complete pulmonary function tests (PFTs). In those patients with lung abnormalities on the CR or PFTs, a high-resolution chest computed tomography scan (HRCT) was performed. We included 40 patients (30 women). Altered PFTs were detected in 18 (45%) of these patients. These cases had a diffusion lung transfer capacity of carbon monoxide (DLCO) of <80% of predicted, without a significant reduction in the forced vital capacity. The HRCT detected abnormalities in 11 of the 18 patients. Diffuse bronchiectasis was the main finding. An inverse correlation between the anti-citrullinated peptide antibody (ACPA) levels and DLCO was found. Asymptomatic lung disease is present in up to 45% of early RA patients and can be determined by PFTs and ACPA levels. PMID- 26846587 TI - New Flexible Channels for Room Temperature Tunneling Field Effect Transistors. AB - Tunneling field effect transistors (TFETs) have been proposed to overcome the fundamental issues of Si based transistors, such as short channel effect, finite leakage current, and high contact resistance. Unfortunately, most if not all TFETs are operational only at cryogenic temperatures. Here we report that iron (Fe) quantum dots functionalized boron nitride nanotubes (QDs-BNNTs) can be used as the flexible tunneling channels of TFETs at room temperatures. The electrical insulating BNNTs are used as the one-dimensional (1D) substrates to confine the uniform formation of Fe QDs on their surface as the flexible tunneling channel. Consistent semiconductor-like transport behaviors under various bending conditions are detected by scanning tunneling spectroscopy in a transmission electron microscopy system (in-situ STM-TEM). As suggested by computer simulation, the uniform distribution of Fe QDs enable an averaging effect on the possible electron tunneling pathways, which is responsible for the consistent transport properties that are not sensitive to bending. PMID- 26846588 TI - Efficacy and Safety of an Aclidinium Bromide Treatment for 12 Weeks or Longer in Patients with Moderate-To-Severe COPD: A Meta-Analysis. AB - BACKGROUND: Bronchodilators are commonly used to manage patients with stable chronic obstructive pulmonary disease (COPD). This meta-analysis assessed the efficacy of aclidinium bromide with respect to clinical events, health-related quality of life and symptom scales, pulmonary function, and safety among patients with stable COPD. METHODS: A comprehensive search of MEDLINE, EMBASE, CINAHL and the Cochrane Library databases was undertaken to identify randomized controlled trials (RCTs) that compared aclidinium with placebo, treatment over at least 12 weeks. Trials were measured using either odds ratios (OR) or mean differences (MD) with 95% confidence intervals (CI). RESULTS: Seven studies, containing 7001 patients, were included in this meta-analysis. Compared with placebo, aclidinium bromide reduced the incidence of exacerbation-related hospitalizations (OR 0.64; 95% CI 0.47 to 0.89) and improved quality of life as measured by a lower total George's Respiratory Questionnaire [SGRQ] score (MD -2.34; 95% CI -3.18 to -1.51) and attenuated dyspnea symptom as assessed by changes in the Transitional Dyspnea Index [TDI] (MD 0.76; 95% CI 0.43 to 1.10). Similar changes were observed with regard to trough FEV1 and FVC and peak FEV1 and FVC. No significant differences were observed with regard to all-cause mortality, COPD exacerbations, non-fatal serious adverse events or cardiac adverse events. CONCLUSIONS: Aclidinium reduced the incidence of exacerbation-related hospitalizations and improved quality of life, COPD symptoms and pulmonary function. In addition, aclidinium did not increase the incidence of non-fatal serious adverse events, cardiac adverse events, or COPD exacerbations and was not associated with increased mortality. PMID- 26846589 TI - First-trimester screening with specific algorithms for early- and late-onset fetal growth restriction. AB - OBJECTIVE: To develop optimal first-trimester algorithms for the prediction of early and late fetal growth restriction (FGR). METHODS: This was a prospective cohort study of singleton pregnancies undergoing first-trimester screening. FGR was defined as an ultrasound estimated fetal weight < 10(th) percentile plus Doppler abnormalities or a birth weight < 3(rd) percentile. Logistic regression based predictive models were developed for predicting early and late FGR (cut off: delivery at 34 weeks). The model included the a-priori risk (maternal characteristics), mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). RESULTS: Of the 9150 pregnancies included, 462 (5%) fetuses were growth restricted: 59 (0.6%) early and 403 (4.4%) late. Significant contributions to the prediction of early FGR were provided by black ethnicity, chronic hypertension, previous FGR, MAP, UtA-PI, PlGF and sFlt-1. The model achieved an overall detection rate (DR) of 86.4% for a 10% false-positive rate (area under the receiver-operating characteristics curve (AUC): 0.93 (95% CI, 0.87-0.98)). The DR was 94.7% for FGR with pre-eclampsia (PE) (64% of cases) and 71.4% for FGR without PE (36% of cases). For late FGR, significant contributions were provided by chronic hypertension, autoimmune disease, previous FGR, smoking status, nulliparity, MAP, UtA-PI, PlGF and sFlt-1. The model achieved a DR of 65.8% for a 10% false-positive rate (AUC: 0.76 (95% CI, 0.73-0.80)). The DR was 70.2% for FGR with PE (12% of cases) and 63.5% for FGR without PE (88% of cases). CONCLUSIONS: The optimal screening algorithm was different for early vs late FGR, supporting the concept that screening for FGR is better performed separately for the two clinical forms. Copyright (c) 2016 ISUOG. Published by John Wiley & Sons Ltd. PMID- 26846590 TI - Invasive floating macrophytes reduce greenhouse gas emissions from a small tropical lake. AB - Floating macrophytes, including water hyacinth (Eichhornia crassipes), are dominant invasive organisms in tropical aquatic systems, and they may play an important role in modifying the gas exchange between water and the atmosphere. However, these systems are underrepresented in global datasets of greenhouse gas (GHG) emissions. This study investigated the carbon (C) turnover and GHG emissions from a small (0.6 km(2)) water-harvesting lake in South India and analysed the effect of floating macrophytes on these emissions. We measured carbon dioxide (CO2) and methane (CH4) emissions with gas chambers in the field as well as water C mineralization rates and physicochemical variables in both the open water and in water within stands of water hyacinths. The CO2 and CH4 emissions from areas covered by water hyacinths were reduced by 57% compared with that of open water. However, the C mineralization rates were not significantly different in the water between the two areas. We conclude that the increased invasion of water hyacinths and other floating macrophytes has the potential to change GHG emissions, a process that might be relevant in regional C budgets. PMID- 26846591 TI - A Randomized, Controlled Trial of a Shared Panel Management Program for Small Practices. AB - OBJECTIVES: To determine whether a shared panel management program was effective at improving quality of care for patients with uncontrolled chronic disease. DATA SOURCES: Data were extracted from electronic health records. STUDY DESIGN: Randomized controlled trial of a panel management program initiated by New York City Department of Health and Mental Hygiene. Patients from 20 practices with an uncontrolled chronic disease and a lapse in care were assigned to the intervention (a phone call requesting that the patient schedule a physician appointment) or usual care. Outcomes were visits to physician practices, body mass index measurement, blood pressure measurement and control, use of antithrombotics, and low-density lipoprotein measurement and control. PRINCIPAL FINDINGS: Panel managers were able to successfully speak with 1,676 patients (14.7 percent of the intervention group). There were no significant differences in outcomes between the intervention and usual care groups. Successfully contacted patients were more likely to have an office visit within 1 year of randomization (45.6 percent [95 percent CI: 22.8, 26.9] vs. 38.1 percent [95 percent CI: 36.8, 39.3]) and more likely to be on antithrombotics (24.4 percent [95 percent CI: 17.7, 31.0]) versus those in the usual care group (17.0 percent [95 percent CI: 13.9, 20.0]) but had no other difference in quality. CONCLUSIONS: A shared, low-intensity panel management program run by a city health department did not improve quality of care for patients with chronic illnesses and lapses in care. PMID- 26846592 TI - Single nucleotide polymorphisms of TNFAIP3 are associated with systemic lupus erythematosus in Han Chinese population. AB - The polymorphisms of tumour necrosis factor alpha-induced protein 3 (TNFAIP3) have been found to associate with several autoimmune diseases. This study aimed to explore the association of single nucleotide polymorphisms (SNPs) of TNFAIP3 gene with systemic lupus erythematosus (SLE) in Han Chinese. Thirty-two SNPs were genotyped in 284 patients with SLE and 630 controls using the ligation detection reaction (LDR) method. The quality control steps and statistical analyses were performed using the PLINK 1.07 package and HAPLOVIEW software. We found that 13 SNPs in TNFAIP3 showed significant association with SLE (P < 1.85 * 10(-3)), and all of them were in high linkage disequilibrium (LD). After conditioning on the SNP rs2230926, other 12 SNPs did not show association (P > 0.27). All 13 SNPs showed most significant association in the dominant model. In haplotype analysis, a long risk SNP haplotype (GCCCGTGTCATGG) showed most significant association (P = 1.00 * 10(-4)). In conclusion, our data suggest that TNFAIP3 is a susceptible gene for SLE in the Han Chinese population. PMID- 26846594 TI - Intraocular pressure is not the only important postoperative variable following vitrectomy. PMID- 26846593 TI - Childhood febrile illness and the risk of myopia in UK Biobank participants. AB - PURPOSE: Historical reports suggest febrile illness during childhood is a risk factor for myopia. The establishment of the UK Biobank provided a unique opportunity to investigate this relationship. PATIENTS AND METHODS: We studied a sample of UK Biobank participants of White ethnicity aged 40-69 years old who underwent autorefraction (N=91 592) and were classified as myopic (<=-0.75 Dioptres (D)), highly myopic (<=-6.00 D), or non-myopic (>-0.75 D). Self-reported age at diagnosis of past medical conditions was ascertained during an interview with a nurse at a Biobank assessment centre. Logistic regression analysis was used to calculate the odds ratio (OR) for myopia or high myopia associated with a diagnosis before age 17 years of each of nine febrile illnesses, after adjusting for potential confounders (age, sex, highest educational qualification, and birth order). RESULTS: Rubella, mumps, and pertussis were associated with myopia: rubella, OR=1.38, 95% CI: 1.03-1.85, P=0.030; mumps, OR=1.32, 95% CI: 1.07-1.64, P=0.010; and pertussis, OR=1.39, 95% CI 1.03-1.87, P=0.029. Measles, rubella, and pertussis were associated with high myopia: measles, OR=1.48, 95% CI: 1.07-2.07, P=0.019; rubella, OR=1.94, 95% CI: 1.12-3.35, P=0.017; and pertussis, OR=2.15, 95% CI: 1.24-3.71, P=0.006. The evidence did not support an interaction between education and febrile illness in explaining the above risks. CONCLUSION: A history of childhood measles, rubella, or pertussis was associated with high myopia, whereas a history of childhood rubella, mumps, or pertussis was associated with any myopia. The reasons for these associations are unclear. PMID- 26846595 TI - Is intraocular pressure the only important postoperative variable? The role of first day postoperative review after vitrectomy. PMID- 26846596 TI - A rapidly emerging ocular zoonosis; Dirofilaria repens. PMID- 26846598 TI - Computational evaluation of aortic occlusion and the proposal of a novel, improved occluder: Constrained endo-aortic balloon occlusion. AB - Because aortic occlusion is arguably one of the most dangerous aortic manipulation maneuvers during cardiac surgery in terms of perioperative ischemic neurological injury, the purpose of this investigation is to assess the structural mechanical impact resulting from the use of existing and newly proposed occluders. Existing (clinically used) occluders considered include different cross-clamps (CCs) and endo-aortic balloon occlusion (EABO). A novel occluder is also introduced, namely, constrained EABO (CEABO), which consists of applying a constrainer externally around the aorta when performing EABO. Computational solid mechanics are employed to investigate each occluder according to a comprehensive list of functional requirements. The potential of a state of occlusion is also considered for the first time. Three different constrainer designs are evaluated for CEABO. Although the CCs were responsible for the highest strains, largest deformation, and most inefficient increase of the occlusion potential, it remains the most stable, simplest, and cheapest occluder. The different CC hinge geometries resulted in poorer performance of CC used for minimally invasive procedures than conventional ones. CEABO with a profiled constrainer successfully addresses the EABO shortcomings of safety, stability, and positioning accuracy, while maintaining its complexities of operation (disadvantage) and yielding additional functionalities (advantage). Moreover, CEABO is able to achieve the previously unattainable potential to provide a clinically determinable state of occlusion. CEABO offers an attractive alternative to the shortcomings of existing occluders, with its design rooted in achieving the highest patient safety. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26846599 TI - A double centre retrospective study into rates of postpartum haemorrhage in women on low molecular weight heparin. PMID- 26846597 TI - The role of structural parameters in DNA cyclization. AB - BACKGROUND: The intrinsic bendability of DNA plays an important role with relevance for myriad of essential cellular mechanisms. The flexibility of a DNA fragment can be experimentally and computationally examined by its propensity for cyclization, quantified by the Jacobson-Stockmayer J factor. In this study, we use a well-established coarse-grained three-dimensional model of DNA and seven distinct sets of experimentally and computationally derived conformational parameters of the double helix to evaluate the role of structural parameters in calculating DNA cyclization. RESULTS: We calculate the cyclization rates of 86 DNA sequences with previously measured J factors and lengths between 57 and 325 bp as well as of 20,000 randomly generated DNA sequences with lengths between 350 and 4000 bp. Our comparison with experimental data is complemented with analysis of simulated data. CONCLUSIONS: Our data demonstrate that all sets of parameters yield very similar results for longer DNA fragments, regardless of the nucleotide sequence, which are in agreement with experimental measurements. However, for DNA fragments shorter than 100 bp, all sets of parameters performed poorly yielding results with several orders of magnitude difference from the experimental measurements. Our data show that DNA cyclization rates calculated using conformational parameters based on nucleosome packaging data are most similar to the experimental measurements. Overall, our study provides a comprehensive large scale assessment of the role of structural parameters in calculating DNA cyclization rates. PMID- 26846601 TI - Can early exercise attenuate muscle atrophy or bone loss after SCI? PMID- 26846600 TI - A new allele conferring resistance to Lysinibacillus sphaericus is detected in low frequency in Culex quinquefasciatus field populations. AB - BACKGROUND: The Cqm1 alpha-glucosidase of Culex quinquefasciatus larvae acts as the midgut receptor for the binary toxin of the biolarvicide Lysinibacillus sphaericus. Mutations within the cqm1 gene can code for aberrant polypeptides that can no longer be properly expressed or bind to the toxin, leading to insect resistance. The cqm1 REC and cqm1 REC-2 alleles were identified in a laboratory selected colony and both displayed mutations that lead to equivalent phenotypes of refractoriness to L. sphaericus. cqm1 REC was first identified as the major resistance allele in this colony but it was subsequently replaced by cqm1 REC-2 , suggesting the better adaptive features of the second allele. The major aim of this study was to evaluate the occurrence of cqm1 REC-2 and track its origin in field populations where cqm1 REC was previously identified. METHODS: The screening of the cqm1 REC-2 allele was based on more than 2000 C. quinquefasciatus larvae from five localities in the city of Recife, Brazil and used a multiplex PCR assay that is also able to identify cqm1 REC . Full-length sequencing of the cqm1 REC-2 and selected cqm1 samples was performed to identify further polymorphisms between these alleles. RESULTS: The cqm1 REC-2 allele was found in field samples, specifically in two heterozygous individuals from a single locality with an overall frequency and distribution much lower than that observed for cqm1 REC . The full-length sequences from these two cqm1 REC-2 copies were almost identical to the cqm1 REC-2 derived from the resistant colony but displayed more than 30 SNPs when compared with cqm1 and cqm1 REC . The cqm1 REC and cqm1 REC-2 resistant alleles were found to be associated with two distinct sets of wild-type cqm1 variants found in field populations. CONCLUSIONS: The cqm1 REC-2 allele occurs in populations in Recife and was probably already present in the samples used to establish the laboratory resistant colony. The data generated indicates that cqm1 REC-2 can be selected in field populations, although its low frequency and distribution in Recife suggest that cqm1 REC-2 presents a lower risk of selection compared to cqm1 REC . PMID- 26846602 TI - Prostate Cancer Stem Cells: Viewing Signaling Cascades at a Finer Resolution. AB - It is becoming characteristically more understandable that within tumor cells, there lies a sub-population of tumor cells with "stem cell" like properties and remarkable ability of self-renewal. Many features of these self-renewing cells are comparable with normal stem cells and are termed as "cancer stem cells". Accumulating experimentally verified data has started to scratch the surface of spatio-temporally dysregulated intracellular signaling cascades in the biology of prostate cancer stem cells. We partition this multicomponent review into how different signaling cascades operate in cancer stem cells and how bioactive ingredients isolated from natural sources may modulate signaling network. PMID- 26846603 TI - Is Ultrasound a Useful Tool to Predict Severe Dengue Infection? AB - OBJECTIVES: To study the role of ultrasound in children with dengue fever and determine its role in predicting the severity of the disease. METHODS: This was a retrospective hospital based study conducted from 1(st) August 2012 to January 31(st) 2015 at a tertiary care hospital in Puducherry. RESULTS: Two hundred and fifty four children were admitted with dengue fever and among them non-severe dengue and severe dengue were seen in 62.6 % and 37.4 % respectively. Mean age of presentation was 7.0 (3.3) years. M: F ratio was 1.2:1 Ultrasound was performed on all children with dengue fever during the critical period of illness as an early sign of plasma leakage and at the time of discharge. The diagnosis was confirmed by NS1 antigen and dengue serology. Ultrasonography showed positive findings in 156 cases (61.4 %) during the critical period of illness. Ultrasound findings were analyzed using logistic regression among severe and non-severe dengue and P value of <0.05 was taken as significant. The common ultrasound findings that were significantly associated with severe dengue infection on univariate analysis were gall bladder wall thickening, ascites, pleural effusion, pericardial effusion, pericholecystic fluid, hepatomegaly, splenomegaly and mesenteric adenopathy. On multivariate analysis, gall bladder thickening and hepatomegaly were significantly associated with severe dengue infection. Gall bladder wall thickening (GBWT) with honeycombing pattern was the most specific finding in severe dengue infection in the study and significantly associated with severe thrombocytopenia (Platelet count <50,000/mm(3)). The clinical improvement coincided with resolving of the ultrasound findings at the time of discharge. CONCLUSIONS: Ultrasound can be used as an early predictor as well as an important prognostic sign for severe dengue infection especially during an epidemic. PMID- 26846604 TI - Re-emergence of Tetanus: Epidemiological Features, Clinical Profile and Outcome from South India. PMID- 26846605 TI - Performance Characterization of an Actively Cooled Repetitive Transcranial Magnetic Stimulation Coil for the Rat. AB - OBJECTIVES: This study characterizes and validates a recently developed dedicated circular rat coil for small animal repetitive Transcranial Magnetic Stimulation (rTMS). MATERIALS AND METHODS: The electric (E) field distribution was calculated in a three-dimensional (3D) spherical rat head model and coil cooling performance was characterized. Motor threshold (MT) in rats (n = 12) was determined using two current directions, MT variability (n = 16) and laterality (n = 11) of the stimulation was assessed. Finally, 2-deoxy-2-((18) F)fluoro-D-glucose ([(18) F] FDG) small animal Positron Emission Tomography (uPET) after sham and 1, 10, and 50 Hz rTMS stimulation (n = 9) with the new Cool-40 Rat Coil (MagVenture, Denmark) was performed. RESULTS: The coil could produce high E-fields of maximum 220 V/m and more than 100 V/m at depths up to 5.3 mm in a ring-shaped distribution. No lateralization of stimulation was observed. Independent of the current direction, reproducible MT measurements were obtained at low percentages (27 +/- 6%) of the maximum machine output (MO, MagPro X100 [MagVenture, Denmark]). At this intensity, rTMS with long pulse trains is feasible (1 Hz: continuous stimulation; 5 Hz: 1000 pulses; 10 Hz and 50 Hz: 272 pulses). When compared to sham, rTMS at different frequencies induced decreases in [(18) F]-FDG uptake bilaterally mainly in dorsal cortical regions (visual, retrosplenial, and somatosensory cortices) and increases mainly in ventral regions (entorhinal cortex and amygdala). CONCLUSION: The coil is suitable for rTMS in rats and achieves unprecedented high E-fields at high stimulation frequencies and long durations with however a rather unfocal rat brain stimulation. Reproducible MEPs as well as alterations in cerebral glucose metabolism following rTMS were demonstrated. PMID- 26846606 TI - Reprint of experiments and theory of (138)La radioactive decay. AB - We measured with unprecedented accuracy key features of the (138)La radioactive decays as beta particle energy distribution from 0.5keV to the end-point and ratios of electron capture probabilities PL/PK, PM/PK and PM/PL. This was achieved by making use of LaBr3:Ce and CeBr3 scintillator detectors. The advantage of the presented technique relies on the double role of LaBr3:Ce as source of (138)La and detector medium resulting in a relatively efficient counting statistics and unaltered beta energy detection. The experimental results are compared to advanced computational techniques and significant deviation is found below 20keV with the computational spectrum showing a 5% excess of beta particle relative to the experimental spectrum at 10keV. PMID- 26846607 TI - Effect of Nd:YAG laser-assisted non-surgical periodontal therapy on clinical periodontal and serum biomarkers in patients with and without coronary artery disease: A short-term pilot study. AB - BACKGROUND/OBJECTIVE: We hypothesized that nonsurgical-periodontal-therapy (NSPT) with adjunct Nd:YAG laser therapy is more effective in reducing periodontal inflammatory parameters (plaque index [PI], bleeding-on-probing [BOP], and probing-pocket-depth [PPD]) and serum interleukin-1beta (IL-1beta) and matrix metalloproteinase-9 (MMP-9) levels in patients with and without coronary artery disease (CAD) than NSPT alone. The aim of this short-term pilot study was to assess the effect of NSPT + Nd:YAG laser therapy on periodontal parameters and serum IL-1beta and MMP-9 levels in patients with and without CAD. STUDY DESIGN: A prospective randomized clinical study was conducted on 87 patients who were divided into two groups: Group-1: 44 patients with CAD and periodontal disease (PD) and Group-2: 43 patients with PD alone. Treatment-wise, these individuals were randomly divided into two subgroups: (i) NSPT alone and (ii) NSPT + Nd:YAG laser therapy. Demographic information was collected using a self-completed questionnaire. Periodontal parameters (PI, BOP, and PPD) and serum IL-1beta and MMP-9 levels were measured at baseline and after 3 months of treatment. P-values <0.05 were considered statistically significant. RESULTS: At 3 months follow-up, PI (P < 0.01), BOP (P < 0.01), PPD >= 4 mm (P < 0.01), and serum IL-1beta (P < 0.01) and MMP-9 (P < 0.01) levels were significantly higher in patients treated with NSPT alone than those treated with NSPT + Nd:YAG laser therapy. Among patients that underwent NSPT + laser therapy in both groups, periodontal parameters and serum IL-1beta, and MMP-9 levels were comparable at 3-months follow-up. CONCLUSION: NSPT + Nd:YAG laser therapy may be more effective in reducing periodontal inflammation and serum IL-1beta and MMP-9 levels in patients with and without CAD than NSPT alone. Lasers Surg. Med. 48:929-935, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26846608 TI - Outbreak of Salmonella Strathcona caused by datterino tomatoes, Denmark, 2011. AB - In September 2011, a patient cluster with a rare Salmonella serotype - Strathcona - was identified in Denmark. An outbreak investigation was initiated to reveal the source in order to stop the outbreak. In addition to hypothesis-generating interviews, comparable analyses of patients' household shopping receipts were conducted. A matched case-control study with 25 cases and 56 population register controls was conducted to test the findings of the hypothesis-generating investigation. In total, 43 cases of Salmonella Strathcona were reported in Denmark. Additionally, 28 cases were reported from Germany, Italy, Austria and Belgium. The results of the investigation in Denmark showed that 8/10 cases had bought datterino tomatoes prior to disease onset. Illness was associated with a specific supermarket chain [matched odds ratio (mOR) 16.9, 95% confidence interval (CI) 2.2-130], and having consumed elongated small tomatoes (OR 28.1, 95% CI 2.6-302). Traceback investigation showed that the tomatoes came from an Italian producer. This outbreak, linked to tomatoes, underpins the growing recognition of the broad source range of Salmonella and the ability of fresh produce to cause multi-country outbreaks. It is important to strengthen the international cooperation between public-health and food-safety authorities in the European Union to investigate future multi-country outbreaks in order to prevent illness from ready-to-eat produce. PMID- 26846609 TI - Course and risk factors for excessive daytime sleepiness in Parkinson's disease. AB - INTRODUCTION: Excessive daytime sleepiness (EDS) is a common feature of Parkinson's disease (PD) that contributes to the disease burden and increases risk of harm. The aim of this study was to examine persistency, cross-sectional and longitudinal associations, and risk factors for EDS in patients with PD. METHODS: Analyses were performed on data from the SCOPA-PROPARK cohort, a 5-year hospital-based longitudinal cohort of over 400 PD patients who were examined annually. Cross-sectional analyses were conducted to evaluate differences between patients with and without EDS at baseline, while linear mixed models using data of all patients were used to identify factors associated with longitudinal changes in SCOPA-SLEEP-Daytime Sleepiness (SCOPA-SLEEP-DS) scores. A survival analysis was done using data of patients without EDS at baseline to identify risk factors for future EDS. RESULTS: EDS proved a non-persistent symptom, although persistency and the proportion of patients with EDS increased with longer follow up. At baseline 43% of patients had EDS, while 46% of patients without EDS at baseline developed this symptom during follow-up. Male gender, poorer nighttime sleep, cognitive and autonomic dysfunction, hallucinations, less severe dyskinesias, dose of dopamine agonists and use of antihypertensives were associated with higher EDS scores over time, while use of benzodiazepines was associated with lower scores. Baseline SCOPA-SLEEP-DS score and PIGD phenotype were risk factors for future EDS. CONCLUSION: With longer disease duration a large proportion of patients develop EDS. Some risk factors are modifiable and patients should be monitored to improve quality of life and reduce risk of harm. PMID- 26846610 TI - Reduced Anticoagulant Effect of Dabigatran in a Patient Receiving Concomitant Phenytoin. AB - Dabigatran, a direct thrombin inhibitor, is an oral anticoagulant indicated for the prevention of stroke in patients with atrial fibrillation (AF) and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. Dabigatran, as well as the other new anticoagulants-rivaroxaban, apixaban, and edoxaban-are substrates for P-glycoprotein (P-gp). Although the U.S. labeling for rivaroxaban and apixaban states to avoid concomitant use with phenytoin, a known P-gp inducer, the U.S. labeling for dabigatran and edoxaban are less clear. We describe the first case report, to our knowledge, documenting a drug interaction between phenytoin and dabigatran by using laboratory measurements of dabigatran serum concentrations. A 45-year-old African-American man was admitted to the inpatient cardiology service following defibrillations from his implantable cardioverter defibrillator. The patient was evaluated and received appropriate antitachycardia pacing for atrial tachyarrhythmias for an episode of ventricular tachycardia (VT), and antiarrhythmic therapy with sotalol was initiated to reduce both his AF and VT burden. On review of the patient's medications for potential interactions, it was discovered that the patient was taking both dabigatran and phenytoin. To determine the magnitude of this drug interaction prior to making a change in his anticoagulation regimen, a dabigatran serum concentration was measured. This concentration was undetectable, indicating that phenytoin had a significant influence on dabigatran's metabolism and that this patient was at high risk for stroke. Clinicians should be aware of this interaction between phenytoin and dabigatran as well as with all other new oral anticoagulants. In patients taking phenytoin who require an anticoagulant, only warfarin should be prescribed to minimize the risk of stroke. In addition, the prescribing information for dabigatran should be updated to include other medications that result in a significant reduction in dabigatran serum concentrations, such as phenytoin. PMID- 26846611 TI - Chronic fatigue syndrome: comparing outcomes in White British and Black and minority ethnic patients after cognitive-behavioural therapy. AB - BACKGROUND: Cognitive-behavioural therapy (CBT) is one of the most promising treatments for chronic fatigue syndrome (CFS). It is unclear whether CBT is effective for Black and minority ethnic (BME) groups. AIMS: To assess the effectiveness of CBT in BME patients compared with White British patients presenting to a specialist CFS service. METHOD: Data from 67 (19.0%) BME participants and 285 (81.0%) White British participants referred to a specialist CFS service in the UK were collected at baseline and after CBT treatment. RESULTS: Pairwise comparisons revealed that both BME participants and White British participants significantly improved on measures of fatigue severity (P<0.001), physical functioning (P<0.001) and work/social adjustment (P<0.001). Independent samples t-tests showed that BME participants improved despite exhibiting significantly higher baseline damage beliefs (P = 0.009), catastrophising (P = 0.024), all-or-nothing behaviour (P = 0.036) and avoidance/resting behaviour (P = 0.001), compared with White British participants. CONCLUSIONS: To our knowledge, this study is the first to indicate that CBT is effective for treating CFS in a group of patients from diverse BME backgrounds. PMID- 26846612 TI - Mindfulness-based cognitive therapy v. group psychoeducation for people with generalised anxiety disorder: randomised controlled trial. AB - BACKGROUND: Research suggests that an 8-week mindfulness-based cognitive therapy (MBCT) course may be effective for generalised anxiety disorder (GAD). AIMS: To compare changes in anxiety levels among participants with GAD randomly assigned to MBCT, cognitive-behavioural therapy-based psychoeducation and usual care. METHOD: In total, 182 participants with GAD were recruited (trial registration number: CUHK_CCT00267) and assigned to the three groups and followed for 5 months after baseline assessment with the two intervention groups followed for an additional 6 months. Primary outcomes were anxiety and worry levels. RESULTS: Linear mixed models demonstrated significant group * time interaction (F(4,148) = 5.10, P = 0.001) effects for decreased anxiety for both the intervention groups relative to usual care. Significant group * time interaction effects were observed for worry and depressive symptoms and mental health-related quality of life for the psychoeducation group only. CONCLUSIONS: These results suggest that both of the interventions appear to be superior to usual care for the reduction of anxiety symptoms. PMID- 26846613 TI - Depressive symptoms and all-cause mortality in people with type 2 diabetes: a focus on potential mechanisms. AB - BACKGROUND: Depression has been associated with increased all-cause mortality in people with type 2 diabetes. AIMS: To test whether anhedonia, dysphoria and anxiety are differentially associated with all-cause mortality and examine symptom-specific behavioural or pathophysiological mechanisms. METHOD: A total of 1465 people completed the Edinburgh Postnatal Depression Scale in 2005 and were followed until death or 31 December 2010. Cox regression analyses compared survival time for people with a low v. high baseline dysphoria/anhedonia/anxiety score and identified mediating mechanisms. RESULTS: After a mean follow-up of 1878 days (s.d. = 306), 139 participants had died. At all time points, people with anhedonia had an almost twofold increased mortality risk compared with those without anhedonia. Physical activity met criteria for mediation. Symptoms of dysphoria and anxiety were not associated with survival time. CONCLUSIONS: Symptoms of anhedonia predicted shorter survival time, whereas dysphoria/anxiety did not. Mechanistic pathways, in particular physical activity, should be explored further. PMID- 26846614 TI - White matter tract integrity in treatment-resistant gambling disorder. AB - BACKGROUND: Gambling disorder is a relatively common psychiatric disorder recently re-classified within the DSM-5 under the category of 'substance-related and addictive disorders'. AIMS: To compare white matter integrity in patients with gambling disorder with healthy controls; to explore relationships between white matter integrity and disease severity in gambling disorder. METHOD: In total, 16 participants with treatment-resistant gambling disorder and 15 healthy controls underwent magnetic resonance imaging (MRI). White matter integrity was analysed using tract-based spatial statistics. RESULTS: Gambling disorder was associated with reduced fractional anisotropy in the corpus callosum and superior longitudinal fasciculus. Fractional anisotropy in distributed white matter tracts elsewhere correlated positively with disease severity. CONCLUSIONS: Reduced corpus callosum fractional anisotropy is suggestive of disorganised/damaged tracts in patients with gambling disorder, and this may represent a trait/vulnerability marker for the disorder. Future research should explore these measures in a larger sample, ideally incorporating a range of imaging markers (for example functional MRI) and enrolling unaffected first-degree relatives of patients. PMID- 26846615 TI - Lymphedema surgery: Patient selection and an overview of surgical techniques. AB - Evaluation of the lymphedema patients with appropriate staging is fundamental for further treatment. Treatment includes compressive decongestive therapy for stage 0 and 1 patients, lymphovenous anastomosis for stage 1 and 2 patients, vascularized lymph node transfer for stage 2 and above patients. Wedge resection, liposuction, and the Charles procedure are alternatives or additions to physiological procedures. The selection of donor lymph node flap and recipient site depends on the patient's lymphedema status and surgeon's expertise. J. Surg. Oncol. 2016;113:923-931. (c) 2016 Wiley Periodicals, Inc. PMID- 26846617 TI - Unusual dimensionality effects and surface charge density in 2D Mg(OH)2. AB - We present two-dimensional Mg(OH)2 sheets and their vertical heterojunctions with CVD-MoS2 for the first time as flexible 2D insulators with anomalous lattice vibration and chemical and physical properties. New hydrothermal crystal growth technique enabled isolation of environmentally stable monolayer Mg(OH)2 sheets. Raman spectroscopy and vibrational calculations reveal that the lattice vibrations of Mg(OH)2 have fundamentally different signature peaks and dimensionality effects compared to other 2D material systems known to date. Sub wavelength electron energy-loss spectroscopy measurements and theoretical calculations show that Mg(OH)2 is a 6 eV direct-gap insulator in 2D, and its optical band gap displays strong band renormalization effects from monolayer to bulk, marking the first experimental confirmation of confinement effects in 2D insulators. Interestingly, 2D-Mg(OH)2 sheets possess rather strong surface polarization (charge) effects which is in contrast to electrically neutral h-BN materials. Using 2D-Mg(OH)2 sheets together with CVD-MoS2 in the vertical stacking shows that a strong change transfer occurs from n-doped CVD-MoS2 sheets to Mg(OH)2, naturally depleting the semiconductor, pushing towards intrinsic doping limit and enhancing overall optical performance of 2D semiconductors. Results not only establish unusual confinement effects in 2D-Mg(OH)2, but also offer novel 2D-insulating material with unique physical, vibrational, and chemical properties for potential applications in flexible optoelectronics. PMID- 26846616 TI - Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere. AB - Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification. PMID- 26846618 TI - Frequency and characteristics of healthcare visits associated with chronic pain: results from a population-based Canadian study. AB - PURPOSE: This study was designed to investigate the role of chronic pain in healthcare visits. The specific objectives were to document the frequency of healthcare visits and to identify characteristics associated with frequent visits. METHODS: This is a secondary analysis of data from a Canadian cross sectional study on chronic pain. One thousand two hundred and ninety-four participants were screened for chronic pain, and 741 reported having "pain or discomfort that had been experienced either all the time or intermittently for at least three months". Data regarding sociodemographics, general health, and healthcare visits were also collected. The frequency of healthcare visits was defined as at or above the 90th percentile for the group. Frequency was calculated for each setting, i.e., physicians' offices (>= 9), emergency departments (>= 1), and other (>= 15). Binary logistic regression analyses were conducted to identify factors associated with frequent visits. RESULTS: Chronic pain increased the frequency of visits to physicians (odds ratio [OR], 4.7; 95% confidence interval [CI], 2.8 to 7.9), emergency departments (OR, 1.4; 95% CI, 1.0 to 2.0), and "other" healthcare professionals (OR, 8.3; 95% CI, 4.5 to 15.5). Having >=3 chronic conditions significantly increased the odds of frequent healthcare visits. CONCLUSION: Interventions aimed at reducing healthcare costs for chronic pain should target individuals living with multiple chronic conditions. Research is needed to develop and test interventions that focus on the needs of these groups. Identifying the risk factors for high healthcare use and improving self-management may reduce healthcare visits. PMID- 26846619 TI - Cerebral tissue oxygen saturation values in volunteers and patients in the lateral decubitus and beach chair positions: a prospective observational study. AB - BACKGROUND: The objective of this study was to describe changes in cerebral tissue oxygen saturation (SctO2) due to changes in body position in healthy volunteers and in patients undergoing surgery under general anesthesia in the beach chair position (BCP) and lateral decubitus position (LDP). METHODS: In this prospective observational study, SctO2 was measured in 85 awake volunteers serially positioned every 15 min, beginning with the supine position (SP) and followed by the beach chair, supine, and lateral decubitus positions. Cerebral tissue oxygen saturation was also measured supine and in either the BCP or the LDP in 195 patients (according to surgical preference) undergoing elective arthroscopic shoulder surgery. We measured the lowest stable SctO2 values in each position as well as changes in blood pressure and heart rate. RESULTS: In healthy volunteers, the median (interquartile range [IQR]) lowest stable SctO2 value in the SP was 69 [66-71] %. A change in position to the BCP caused a small but statistically significant decrease in the median [IQR] lowest SctO2 value to 67 [65-70] % (P = 0.028 compared with baseline). This decrease was associated with an increase in median [IQR] arterial pressure from 83 [78-88] mmHg in the SP to 85 [81-93] mmHg in the BCP (P < 0.001 compared with baseline). In patients undergoing surgery in the BCP, the median [IQR] lowest stable SctO2 value was 55 [51-59] %, which was significantly lower (P < 0.001) than the median [IQR] lowest SctO2 value in patients in the LDP (66 [62-69] %). More patients in the BCP group (57%) showed SctO2 values <= 55% and/or a decrease of >= 20% from baseline (57%) compared with the LDP group (5% and 6%, respectively; P < 0.001 for each comparison). CONCLUSIONS: More than 55% of patients undergoing arthroscopic shoulder surgery in the BCP experience cerebral desaturation events. In volunteers without anesthesia, no desaturation events were observed. The clinical importance of these findings needs further investigation. PMID- 26846620 TI - Dynamic clustering of hazard functions: an application to disease progression in chronic heart failure. AB - We analyse data collected from the administrative datawarehouse of an Italian regional district (Lombardia) concerning patients affected by Chronic Heart Failure. The longitudinal data gathering for each patient hospital readmissions in time, as well as patient-specific covariates, is studied as a realization of non homogeneous Poisson process. Since the aim behind this study is to identify groups of patients behaving similarly in terms of disease progression and then healthcare consumption, we conjectured the time segments between two consecutive hospitalizations to be Weibull distributed in each hidden cluster. Adding a frailty term to take into account the within subjects unknown variability, the corresponding patient-specific hazard functions are reconstructed. Therefore, the comprehensive distribution for each time to event variable is modelled as a Weibull Mixture. We are then able to easily interpret the related hidden groups as healthy, sick, and terminally ill subjects. PMID- 26846621 TI - Quantitative proteomic study of human prostate cancer cells with different metastatic potentials. AB - Metastatic dissemination is a feature of most cancers including prostate cancer (PCa), and is the main cause of treatment failure and mortality. The aim of the study is to explore the mechanisms of PCa metastasis and to search for potential prognostic markers using proteomics. Two-dimensional fluorescent differential gel electrophoresis (2D-DIGE) was used to quantify proteins in normal prostate epithelial cells, bone metastasis-derived PC-3 cells, and visceral metastasis derived PC-3M cells. Metastatic potential was confirmed by flow cytometry, electron microscopy, proliferating cell nuclear antigen assay, and wound healing assay. Differential protein expression was compared between PCa cells with different metastatic potentials (LNcap, DU145, PC-3 and PC-3M) and normal prostate epithelial cells (RWPE-1). Selected candidate proteins in human prostate tissues were analyzed using GOA, UniProt and GeneCards analyses. Eighty-six proteins were differentially expressed between cell lines (>1.5-fold, P<0.05). Among them, twelve proteins were identified by MALDI-TOF-MS. One protein was upregulated in normal prostate epithelial cells, nine proteins were upregulated in PC-3, and two proteins were upregulated in PC-3M. Proteins were divided into five groups according to their functions. The SETDB1 protein was closely associated with the prognosis of PCa. Bioinformatics suggested that SETDB1 might promote PCa bone metastasis through the WNT pathway. In conclusion, SETDB1 might be associated with the development of bone metastases from PCa. Further study is necessary to assess its exact role in PCa. PMID- 26846622 TI - Metalloproteinases 2 and 9 Immunoexpression in Periapical Lesions from Primary Endodontic Infection: Possible Relationship with the Histopathological Diagnosis and the Presence of Pain. AB - INTRODUCTION: The aim of this study was to evaluate the possible associations among the histopathological diagnosis, the inflammatory infiltrate profile, the presence of pain, and the immunoexpression of matrix metalloproteinases MMP-2 and MMP-9 in periapical lesions from primary endodontic infection. METHODS: Fifty-one primary periapical lesions obtained from extracted teeth were selected for this study. Patients were previously evaluated for the presence of pain and sinus tract related to the tooth to be extracted. Tissues were processed for microscopic examination and MMP-2 and MMP-9 immunoexpression. Microscopically, samples were classified as periapical granulomas or periapical cysts and the inflammatory infiltrate as chronic or mixed. The percentage of immunopositive cells for MMP-2 and MMP-9 of each case was performed based on 10 consecutive microscopic fields. The Student t or chi-square tests were used in the statistical analysis. RESULTS: Of the total, 28 cases were classified as periapical granulomas (54.90%) and 23 cases as periapical cysts (45.10%). Seventeen patients (33.33%) reported pain associated with the extracted tooth, with 12 cases of periapical granulomas (70.58%) and 5 cases of periapical cysts (29.42%). All cases showed immunopositivity for MMP-2 and MMP-9 in a high percentage of cells, mainly in the cytoplasm of the leukocytes. MMP-2 was expressed more in periapical granulomas than periapical cysts (P < .05) and in symptomatic cases (P < .05). CONCLUSIONS: According to the results, we may conclude that MMP-2 and MMP-9 are highly expressed in periapical lesions from a primary endodontic infection. Moreover, we may suggest MMP-2 is expressed more in periapical granuloma and in cases associated with pain. PMID- 26846623 TI - Yeast-generated virus-like particles as antigens for detection of human bocavirus 1-4 specific antibodies in human serum. AB - Human bocaviruses (HBoV) are non-enveloped, single-stranded DNA viruses, classified into the genus Bocavirus in the family Parvoviridae. Self-assembled virus-like particles (VLPs) composed of the major capsid protein VP2 of HBoV1-4 and mosaic VLPs composed of both VP2 and VP1 capsid proteins of HBoV1 were generated in yeast Saccharomyces cerevisiae and used to detect HBoV-specific IgG in human serum. Recombinant HBoV VLPs were similar to native HBoV particles in size and morphology. The prevalence of HBoV infection in a group of Lithuanian patients with clinical symptoms of respiratory tract infection was studied using purified yeast-generated VLPs as antigens in a competitive enzyme immunoassay (EIA). After depletion of cross-reactive antibodies, the seroprevalence of HBoV1 was 44.2 % and the seroprevalence of HBoV2-4 was 35.7 %. Mosaic VLPs consisting of HBoV1 VP1 and VP2 proteins showed a stronger reactivity with HBoV1 IgG positive human serum specimens, and two equivocal serum specimens were reinterpreted as positive. Thus, mosaic VLPs offer a more sensitive tool for HBoV1 serology than currently available serodiagnostics tests based on VP2 VLPs. In conclusion, yeast S. cerevisiae represents an efficient expression system for generating recombinant HBoV1-4 VLPs of diagnostic relevance. PMID- 26846624 TI - RNA binding protein Pub1p regulates glycerol production and stress tolerance by controlling Gpd1p activity during winemaking. AB - Glycerol is a key yeast metabolite in winemaking because it contributes to improve the organoleptic properties of wine. It is also a cellular protective molecule that enhances the tolerance of yeasts to osmotic stress and promotes longevity. Thus, its production increases by genetic manipulation, which is of biotechnological and basic interest. Glycerol is produced by diverting glycolytic glyceraldehyde-3-phosphate through the action of glycerol-3-phosphate dehydrogenase (coded by genes GPD1 and GPD2). Here, we demonstrate that RNA binding protein Pub1p regulates glycerol production by controlling Gpd1p activity. Its deletion does not alter GPD1 mRNA levels, but protein levels and enzymatic activity increase, which explains the higher intracellular glycerol concentration and greater tolerance to osmotic stress of the pub1? mutant. PUB1 deletion also enhances the activity of nicotinamidase, a longevity-promoting enzyme. Both enzymatic activities are partially located in peroxisomes, and we detected peroxisome formation during wine fermentation. The role of Pub1p in life span control depends on nutrient conditions and is related with the TOR pathway, and a major connection between RNA metabolism and the nutrient signaling response is established. PMID- 26846625 TI - RGD and polyhistidine tumor homing peptides potentiates the action of human Maspin as an antineoplastic candidate. AB - Maspin, a non-inhibitory member of serine protease family, acts as an effective tumor suppressor by inhibiting cell inhesion and mobility. We found that exogenous wild-type rMaspin had a low effect on tumor growth in vivo. However, when the peptide Arg-Gly-Asp-hexahistidine (RGD-6His) was introduced into rMaspin, the modified rMaspin showed significant inhibitory activity in angiogenic assays and tumor-bearing animal models. Overall, our data suggested that both the RGD and hexahistidine fragments contributed to improve the fusion protein activity and polyhistidine peptide could be considered as flexible linker to separate RGD and Maspin moieties to avoid function interference. Besides, it is an efficient tag to achieve purified recombinant proteins. Furthermore, rMaspin fusing with RGD and hexahistidine could be a viable anticancer candidate. PMID- 26846626 TI - Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats. AB - The aim of the present study was to investigate the age-related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase-3). In addition, the expression of PPAR-gamma and Bcl-2 were progressively reduced with increasing age in the SHR group. The 32 and 64-week-old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro-apoptotic proteins compared with age-matched WKY rats, which was accompanied by reduced expression of PPAR-gamma. Compared with the 16 and 32-week-old WKY group, the 64-week-old WKY rats exhibited increased oxidative stress and pro-apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR-gamma may contribute to the age-related brain damage in SHRs. PMID- 26846627 TI - Sociocultural Barriers to Lung Cancer Screening Among Korean Immigrant Men. AB - Lung cancer is a commonly occurring cancer among Korean American men. Korean Americans have lower rates of cancer screening participation than other Asian American sub-groups. However, little is known about factors that influence the cancer screening behavior of Korean immigrants. The purpose of this study was to explore facilitators of and barriers to lung cancer screening (i.e., low dose CT of the chest) among Korean immigrant men, using qualitative individual interviews and focus groups. A convenience sample of 24 Korean men who were immigrants, Washington State residents, able to speak Korean, aged 55-79, and eligible for lung cancer screening (based on current guidelines) were recruited from Korean churches and senior centers. Five focus groups (that included between two and five men) and nine individual interviews were conducted. Content analysis was used to analyze the qualitative data. Facilitators of lung cancer screening included perceptions about positive aspects of the health care system in South Korea, recommendations from others (physicians, family members, and community organizations), existing health problems and respiratory symptoms, interest in health, and the health consequences of aging. Barriers included costs of health care in the US, lack of time, lack of knowledge (about lung cancer and screening), attitudes about prevention, and lack of physician recommendation. This study adds new knowledge to a field where little information is available. It also lays the groundwork for developing culturally relevant lung cancer screening interventions for Korean Americans and the health care providers who serve them. PMID- 26846629 TI - [Hypertension treatment and evolving role of angiotension receptor blockers in recent guidelines]. AB - It was estimated that, total number of adults with hypertension was approximately 1 billion worldwide. This number was predicted to increase to a total of 1.5 billion in 2025. Hypertension is the most important risk factor for cardiovascular morbidity and mortality. The relationship between blood pressure and risk of cardiovascular events is continuous, consistent, and independent of other risk factors. The higher the blood pressure, the greater the possibility of heart attack, heart failure, stroke, and kidney diseases. The main purpose of hypertension treatment is to reduce the cardiovascular and renal morbidity and mortality. In this review, the principles of pharmalogical therapy and evolving role of angiotension receptor blockers in hypertension will be summarised according to recent guidelines. PMID- 26846630 TI - [The role of angiotensin-receptor blockers in cardiovascular processes]. AB - Angiotensin-receptor blockers (ARBs) are frequently used in cardiology practice. Thanks to their potent antihypertensive effects, and lower side effect profiles, these drugs are well tolerated, and used for various indications in the field of cardiovascular medicine. This article summarizes clinical fields, and large-scale clinical studies where efficacy of ARBs has been demonstrated. PMID- 26846628 TI - Review: Approaches to the Viral Extraction, Detection, and Identification of Hepatitis Viruses, HAV and HEV, in Foods. AB - Although the incidence rate of hepatitis A virus (HAV) infection has been on the decline in developed countries, in part due to immunization availability, high profile outbreaks continue to be reported. Hepatitis E virus has been recognized as an emerging pathogen in industrialized countries. While associated with waterborne illnesses, particularly in undeveloped countries, several animal species have been identified as reservoirs for the virus. Consequently, the potential of zoonotic transmission exists as a function of the consumption of infected animals. In this review we provide a comparative overview of these two virus species with regard to their known virus properties, discuss extraction methodologies, and describe some basic principles and methodology applied toward the isolation of these viruses (as particles or their isolated genomes) from food commodities. We also discuss the challenges that remain as experimental hurdles to extraction of such viruses from food. As HAV has been the most extensively studied with regard to virus detection in foods, it often serves as a model virus for current and future development of sample preparation methodology for foodborne virus detection. Lastly, we discuss the application and role of current and developing technologies in the post-extraction detection and identification of these viruses from foods. PMID- 26846631 TI - [ARB's in combination therapy]. AB - Combination therapy is needed to achieve adequate control of blood pressure in most patients, especially those with systolic blood pressure >=160 mmHg or diastolic >=100 mmHg. Hypertension guidelines recommend the combination of at least two drugs with complementary mechanisms of action to achieve blood pressure control. In combination therapy, there are physiological and pharmacological synergies between different classes of agents, which cause a greater blood pressure reduction and fewer side-effects. Renin-angiotensin-aldosterone system blockade is a cornerstone of antihypertensive therapy. Many studies showed the effectivenes of angiotensin receptor blocker (ARB) in patients with hypertension, and they are among those most widely used in antihypertensive therapy. The combination of ARBs with either a diuretic or a calcium antagonist are among the preferred combinations. These combinations are well tolerated, effective, and causes blood pressure reductions and control rates than those that can be achieved with monotherapy. Olmesartan is an angiotensin II receptor antagonist which is widely examined in combination of either hydrochlorothiazide or amlodipine, showing improvements in antihypertensive efficacy with good tolerability. The aim of this review was to evaluate the combination of ARBs with diuretic and calcium channel blockers. PMID- 26846633 TI - Recounting Cardiac Cellular Composition. PMID- 26846634 TI - Foiling IDOL to Help Control Cholesterol. PMID- 26846632 TI - Regulation of Notch-mediated transcription by a bovine herpesvirus 1 encoded protein (ORF2) that is expressed in latently infected sensory neurons. AB - Bovine herpesvirus 1 (BoHV-1) is an Alphaherpesvirinae subfamily member that establishes life-long latency in sensory neurons. The latency-related RNA (LR RNA) is abundantly expressed during latency. An LR mutant virus containing stop codons at the amino-terminus of open reading frame (ORF)2 does not reactivate from latency and replicates less efficiently in tonsils and trigeminal ganglia. ORF2 inhibits apoptosis, interacts with Notch family members, and interferes with Notch-dependent transcription suggesting ORF2 expression enhances survival of infected neurons. The Notch signaling pathway is crucial for neuronal differentiation and survival suggesting that interactions between ORF2 and Notch family members regulate certain aspects of latency. Consequently, for this study, we compared whether ORF2 interfered with the four mammalian Notch family members. ORF2 consistently interfered with Notch1-3-mediated transactivation of three cellular promoters. Conversely, Notch4-mediated transcription was not consistently inhibited by ORF2. Electrophoretic shift mobility assays using four copies of a consensus-DNA binding site for Notch/CSL (core binding factor (CBF) 1, Suppressor of Hairless, Lag-2) as a probe revealed ORF2 interfered with Notch1 and 3 interactions with a CSL family member bound to DNA. Additional studies demonstrated ORF2 enhances neurite sprouting in mouse neuroblastoma cells that express Notch1-3, but not Notch4. Collectively, these studies indicate that ORF2 inhibits Notch-mediated transcription and signaling by interfering with Notch interacting with CSL bound to DNA. PMID- 26846636 TI - Understanding Intracellular Signaling Advances Cardiac Reprogramming Technology Toward Clinical Applications. PMID- 26846635 TI - Blood-Derived Extracellular RNA and Platelet Pathobiology: Adding Pieces to a Complex Circulating Puzzle. PMID- 26846637 TI - Central Artery Stiffness in Hypertension and Aging: A Problem With Cause and Consequence. PMID- 26846638 TI - Murine Models Demonstrate Distinct Vasculogenic and Cardiomyogenic cKit+ Lineages in the Heart. AB - After 2 recent genetic studies in mice addressing the developmental origins and regenerative activity of cardiac cKit+ cells, 2 additional reports by Sultana et al and Liu et al provide further information on the expression of cKit in the embryonic and adult hearts. Here, we synthesize the findings from the 4 distinct cKit models to gain insights into the biology of this important cell type. PMID- 26846640 TI - RNA Splicing: Regulation and Dysregulation in the Heart. AB - RNA splicing represents a post-transcriptional mechanism to generate multiple functional RNAs or proteins from a single transcript. The evolution of RNA splicing is a prime example of the Darwinian function follows form concept. A mutation that leads to a new mRNA (form) that encodes for a new functional protein (function) is likely to be retained, and this way, the genome has gradually evolved to encode for genes with multiple isoforms, thereby creating an enormously diverse transcriptome. Advances in technologies to characterize RNA populations have led to a better understanding of RNA processing in health and disease. In the heart, alternative splicing is increasingly being recognized as an important layer of post-transcriptional gene regulation. Moreover, the recent identification of several cardiac splice factors, such as RNA-binding motif protein 20 and SF3B1, not only provided important insight into the mechanisms underlying alternative splicing but also revealed how these splicing factors impact functional properties of the heart. Here, we review our current knowledge of alternative splicing in the heart, with a particular focus on the major and minor spliceosome, the factors controlling RNA splicing, and the role of alternative splicing in cardiac development and disease. PMID- 26846639 TI - Statistical Methods for Cardiovascular Researchers. AB - RATIONALE: Biostatistics continues to play an essential role in contemporary cardiovascular investigations, but successful implementation of biostatistical methods can be complex. OBJECTIVE: To present the rationale behind statistical applications and to review useful tools for cardiology research. METHODS AND RESULTS: Prospective declaration of the research question, clear methodology, and study execution that adheres to the protocol together and serve as the critical foundation of a research endeavor. Both parametric and distribution-free measures of central tendency and dispersion are presented. T testing, ANOVA, and regression analyses are reviewed. Survival analysis, logistic regression, and interim monitoring are also discussed. Finally, common weaknesses in statistical analyses are considered. CONCLUSIONS: Biostatistics can be productively applied to cardiovascular research if investigators (1) develop and rely on a well written protocol and analysis plan, (2) consult with a biostatistician when necessary, and (3) write results clearly, differentiating confirmatory from exploratory findings. PMID- 26846641 TI - Extracellular Ribonucleic Acids (RNA) Enter the Stage in Cardiovascular Disease. AB - Inflammatory and ischemic cardiovascular diseases, especially atherosclerosis and myocardial infarction, remain the number one cause of death in the Western world, whereas the therapeutic options currently available are still limited. Several recent findings have indicated that nucleic acids, particularly extracellular ribosomal RNA and micro-RNAs, significantly contribute to the adverse outcome of atherosclerosis, myocardial infarction, and other cardiovascular diseases. Extracellular RNAs act as novel danger-associated molecular pattern signals and potent cofactors in cardiovascular inflammation and thrombosis, particularly when accumulating in the extracellular space under tissue-damaging or pathological conditions. In this concise review article, the different entities of extracellular RNAs, their cellular sources, and their putative functional contribution to the pathogenesis of cardiovascular diseases will be discussed. In fact, it remains a tightrope walk for these polyanionic molecules outside cells to promote defense reactions on the one side but to provoke cardiovascular disease development on the other side, dependent on their concentration, the environmental conditions, and the cellular stimuli engaged. Thus, we will discuss the mechanisms and cellular responses by which extracellular RNAs operate between defense and disease. Finally, natural counteracting molecules, such as RNase1, will be focused on to elaborate their protective functions in the context of inflammatory and ischemic cardiovascular diseases with the possibility to apply them as novel interventional strategies. PMID- 26846642 TI - New Management Strategies in Heart Failure. AB - Despite >100 clinical trials, only 2 new drugs had been approved by the US Food and Drug Administration for the treatment of chronic heart failure in more than a decade: the aldosterone antagonist eplerenone in 2003 and a fixed dose combination of hydralazine-isosorbide dinitrate in 2005. In contrast, 2015 has witnessed the Food and Drug Administration approval of 2 new drugs, both for the treatment of chronic heart failure with reduced ejection fraction: ivabradine and another combination drug, sacubitril/valsartan or LCZ696. Seemingly overnight, a range of therapeutic possibilities, evoking new physiological mechanisms, promise great hope for a disease that often carries a prognosis worse than many forms of cancer. Importantly, the newly available therapies represent a culmination of basic and translational research that actually spans many decades. This review will summarize newer drugs currently being used in the treatment of heart failure, as well as newer strategies increasingly explored for their utility during the stages of the heart failure syndrome. PMID- 26846643 TI - Myocarditis. AB - Viral myocarditis remains a prominent infectious-inflammatory disease for patients throughout the lifespan. The condition presents several challenges including varied modes of clinical presentation, a range of timepoints when patients come to attention, a diversity of approaches to diagnosis, a spectrum of clinical courses, and unsettled perspectives on therapeutics in different patient settings and in the face of different viral pathogens. In this review, we examine current knowledge about viral heart disease and especially provide information on evolving understanding of mechanisms of disease and efforts by investigators to identify and evaluate potential therapeutic avenues for intervention. PMID- 26846644 TI - Lymphatic System in Cardiovascular Medicine. AB - The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. It actively regulates tissue fluid homeostasis, absorption of gastrointestinal lipids, and trafficking of antigen-presenting cells and lymphocytes to lymphoid organs and on to the systemic circulation. The cardinal manifestation of lymphatic malfunction is lymphedema. Recent research has implicated the lymphatic system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial infarction. Here, we review the most recent advances in the field of lymphatic vascular biology, with a focus on cardiovascular disease. PMID- 26846645 TI - Correction. PMID- 26846646 TI - Correction. PMID- 26846647 TI - Notice of Retraction. PMID- 26846648 TI - Study of thermoluminescence (TL) and optically stimulated luminescence (OSL) from alpha-keratin protein found in human hairs and nails: potential use in radiation dosimetry. AB - The thermoluminescence (TL) and optically stimulated luminescence (OSL) properties of human nails and hairs containing alpha-keratin proteins have been investigated. For the present studies, black hairs and finger nails were selectively collected from individuals with ages between 25 and 35 years. The collected hairs/nails were cut to a size of < 1 mm and cleaned with distilled water to remove dirt and other potential physical sources of contamination. All samples were optically beached with 470 nm of LED light at 60 mW/cm(2) intensity and irradiated by a (60)Co gamma source. The hair and nail samples showed overlapping multiple TL glow peaks in the temperature range from 70 to 210 degrees C. Continuous wave (CW)-OSL measurements of hair samples at a wavelength of 470 nm showed the presence of two distinct OSL components with photoionization cross section (PIC) values of about 1.65 * 10(-18) cm(2) and about 3.48 * 10(-19) cm(2), while measurements of nail samples showed PIC values of about 6.98 * 10( 18) cm(2) and about 8.7 * 10(-19) cm(2), respectively. This difference in PIC values for hair and nail samples from the same individual is attributed to different arrangement of alpha-keratin protein concentrations in the samples. The OSL sensitivity was found to vary +/- 5 times among nail and hair samples from different individuals, with significant fading (60% in 11 h) at room temperature. The remaining signal (after fading) can be useful for dose estimation when a highly sensitive OSL reader is used. In the absorbed dose range of 100 mGy-100 Gy, both the TL and OSL signals of hair and nail samples showed linear dose dependence. The results obtained in the present study suggest that OSL using hair and nail samples may provide a supplementary method of dose estimation in radiological and nuclear emergencies. PMID- 26846649 TI - Destructive Hard Palate Mass. PMID- 26846652 TI - BREACHING THE SEXUAL BOUNDARIES IN THE DOCTOR-PATIENT RELATIONSHIP: SHOULD ENGLISH LAW RECOGNISE FIDUCIARY DUTIES? AB - In this article, I argue that sexual exploitation in the doctor-patient relationship would be dealt with more appropriately by the law in England and Wales on the basis of a breach of fiduciary duty. Three different types of sexual boundary breaches are discussed, and the particular focus is on breaches where the patient's consent is obtained through inducement. I contend that current avenues of redress do not clearly catch this behaviour and, moreover, they fail to capture the essence of the wrong committed by the doctor-the knowing breach of trust for self-gain-and the calculated way in which consent is induced. Finally, I demonstrate that the fiduciary approach is compatible with the contemporary pro patient autonomy model of the doctor-patient relationship. PMID- 26846651 TI - Multidrug Resistance Related to Biofilm Formation in Acinetobacter baumannii and Klebsiella pneumoniae Clinical Strains from Different Pulsotypes. AB - The emergence of Acinetobacter baumannii and Klebsiella pneumoniae strains in the hospital environment has been associated with the presence of multiple genetic elements, virulence factors and the ability to form biofilms. This study evaluated the biofilm formation ability of clinical and environmental A. baumannii and K. pneumoniae strains, isolated from various sources and presenting different molecular characteristics, resistance profiles and pulsed-field gel electrophoresis patterns. Fifty-three isolates were recovered from 2009 to 2014 in a Brazilian university hospital. Investigation of biofilm formation was performed for 10 strains of each species assessed by an initial adhesion assay, biofilm cell concentration and biofilm biomass, evaluated by quantitative assays in replicates, in three independent experiments. All strains of A. baumannii were able to attach to polystyrene plates, although two strains adhered to a lesser degree than the control. K. pneumoniae strains showed opposite behaviour, where only three strains adhered significantly when compared to the control. Quantitative evaluation revealed that in five A. baumannii and four K. pneumoniae isolates the biomass production could be characterised as moderate. None of the isolates were strong biofilm producers. Our results demonstrate: (1) biofilm formation is a heterogeneous property amongst A. baumannii and K. pneumoniae clinical strains and it was not associated with certain clonal types; (2) no relationship between multidrug resistance and biofilm production was observed; (3) more virulent K. pneumoniae strains tended to present higher production of biofilm. PMID- 26846650 TI - Targeting Met and VEGFR Axis in Metastatic Castration-Resistant Prostate Cancer: 'Game Over'? AB - Despite recent advances that have been made in the therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC), effective management of bone metastases remains a key goal not yet reached. The receptor tyrosine kinase MET and the vascular endothelial growth factor receptor (VEGFR) seem to play an important role in prostate cancer progression and pathological bone turnover, representing potential targets for improving clinical outcomes in mCRPC. Studies evaluating agents that target one or both these pathways have demonstrated modest activity but no improvement in overall survival. Nevertheless, this therapeutic strategy seems to still be a promising and engaging area of prostate cancer research and the interest in better understanding the MET/VEGFR axis and the mechanism of action of these inhibitors is growing. This review describes the rationale for targeting MET and VEGFR pathway in mCRPC and provides the clinical data available to date and an update on ongoing trials. PMID- 26846654 TI - Nano-sized Mn oxide/agglomerated silsesquioxane composite as a good catalyst for water oxidation. AB - Water splitting to hydrogen and oxygen is an important reaction to store sustainable energies, and water oxidation is identified as the bottleneck for water splitting because it requires the high activation energy to perform. Herein a nano-sized Mn oxide/agglomerated silsesquioxane composite was used to synthesize an efficient catalyst for water oxidation. The composite was synthesized by a straightforward and simple procedure and characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, Raman spectroscopy, dynamic light scattering, X-ray diffraction spectrometry, and electrochemical methods. Silsesquioxane causes good dispersion of Mn in the composite. The water-oxidizing activity of this composite was studied in the presence of cerium(IV) ammonium nitrate. The composite at the best calcination temperature (300 degrees C) shows a turnover frequency 0.3 (mmol O2/mol Mn.s). Regarding the low-cost, environmentally friendly precursors, simple synthesis, and efficiency for water oxidation, the composite is a promising catalyst that can be used in artificial photosynthetic systems for water splitting. We used Agglomerated silsesquioxane as a support for nano-sized Mn oxide to synthesize a good water-oxidizing catalyst. PMID- 26846653 TI - Obstacles in the quantification of the cyclic electron flux around Photosystem I in leaves of C3 plants. AB - Sixty years ago Arnon and co-workers discovered photophosphorylation driven by a cyclic electron flux (CEF) around Photosystem I. Since then understanding the physiological roles and the regulation of CEF has progressed, mainly via genetic approaches. One basic problem remains, however: quantifying CEF in the absence of a net product. Quantification of CEF under physiological conditions is a crucial prerequisite for investigating the physiological roles of CEF. Here we summarize current progress in methods of CEF quantification in leaves and, in some cases, in isolated thylakoids, of C3 plants. Evidently, all present methods have their own shortcomings. We conclude that to quantify CEF in vivo, the best way currently is to measure the electron flux through PS I (ETR1) and that through PS II and PS I in series (ETR2) for the whole leaf tissue under identical conditions. The difference between ETR1 and ETR2 is an upper estimate of CEF, mainly consisting, in C3 plants, of a major PGR5-PGRL1-dependent CEF component and a minor chloroplast NDH-dependent component, where PGR5 stands for Proton Gradient Regulation 5 protein, PGRL1 for PGR5-like photosynthesis phenotype 1, and NDH for Chloroplast NADH dehydrogenase-like complex. These two CEF components can be separated by the use of antimycin A to inhibit the former (major) component. Membrane inlet mass spectrometry utilizing stable oxygen isotopes provides a reliable estimation of ETR2, whilst ETR1 can be estimated from a method based on the photochemical yield of PS I, Y(I). However, some issues for the recommended method remain unresolved. PMID- 26846655 TI - Functional outcomes after peroneal tendoscopy in the treatment of peroneal tendon disorders. AB - PURPOSE: The primary purpose of this study was to evaluate clinical outcomes following peroneal tendoscopy for the treatment of peroneal pathology. Correlation between pre-operative magnetic resonance imaging (MRI) and peroneal tendoscopic diagnostic findings was also assessed. METHODS: Twenty-three patients with a mean age of 34 +/- 8.8 years undergoing peroneal tendoscopy were pre- and post-operatively assessed with the foot and ankle outcome score (FAOS) and the Short Form-12 (SF-12) outcome questionnaires. Follow-up was over 24 months in all patients. The sensitivity and specificity of MRI were calculated in comparison with peroneal tendoscopy, including the positive predictive value (PPV). RESULTS: Both the FAOS and the SF-12 improved significantly (p < 0.05) at a mean follow-up of 33 +/- 7.3 months significantly. MRI showed an overall sensitivity of 0.90 (95% confidence interval (CI) = 0.82-0.95) and specificity of 0.72 (95% CI 0.62 0.80). The PPV for MRI diagnosis of peroneal tendon pathology was 0.76 (95% CI 0.68-0.83). CONCLUSIONS: The current study found good clinical outcomes in patients with peroneal tendon disorders, treated with peroneal tendoscopy. Although a relatively small number of patients were included, the study suggests good correlation between tendoscopic findings and pre-operative MRI findings of peroneal tendon pathology, supporting the use of MRI as a useful diagnostic modality for suspected peroneal tendon disorders. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 26846656 TI - Clinical outcome of increased flexion gap after total knee arthroplasty. Can controlled gap imbalance improve knee flexion? AB - PURPOSE: Increased range of motion (ROM) while maintaining joint stability is the goal of modern total knee arthroplasty (TKA). A biomechanical study has shown that small increases in flexion gap result in decreased tibiofemoral force beyond 90 degrees flexion. The purpose of this paper was to investigate clinical implications of controlled increased flexion gap. METHODS: Four hundred and four TKAs were allocated into one of two groups and analysed retrospectively. In the first group (n = 352), flexion gap exceeded extension gap by 2.5 mm, while in the second group (n = 52) flexion gap was equal to the extension gap. The procedures were performed from 2008 to 2012. The patients were reviewed 12 months postoperatively. Objective clinical results were assessed for ROM, mediolateral and sagittal stability. Patient-reported outcome measures were the WOMAC score and the Forgotten Joint Score (FJS-12). RESULTS: After categorizing postoperative flexion into three groups (poor < 90 degrees , satisfactory 91 degrees -119 degrees , good >= 120 degrees ) significantly more patients in group 1 achieved satisfactory or good ROM (p = 0.006). Group 1 also showed a significantly higher mean FJS-12 (group 1: 73, group 2: 61, p = 0.02). The mean WOMAC score was 11 in the first and 14 in the second group (n.s.). Increase in flexion gap did not influence knee stability. CONCLUSIONS: The clinical relevance of this study is that a controlled flexion gap increase of 2.5 mm may have a positive effect on postoperative flexion and patient satisfaction after TKA. Neither knee stability in the coronal and sagittal planes nor complications were influenced by a controlled increase in flexion gap. LEVEL OF EVIDENCE: III. PMID- 26846657 TI - Navigation-based tibial rotation at 90 degrees of flexion is associated with better range of motion in navigated total knee arthroplasty. AB - PURPOSE: In clinical practice, people with better femorotibial rotation in the flexed position often achieve a favourable postoperative maximum flexion angle (MFA). However, no objective data have been reported to support this clinical observation. In the present study, we aimed to investigate the correlation between the amount of intraoperative rotation and the pre- and postoperative flexion angles. METHODS: Fifty-five patients with varus osteoarthritis undergoing computer-assisted posterior-stabilized total knee arthroplasty (TKA) were enrolled. After registration, rotational stress was applied towards the knee joint, and the rotational angles were recorded by using a navigation system at maximum extension and 90 degrees of flexion. After implantation, rotational stress was applied for a second time, and the angles were recorded once more. The MFA was measured before surgery and 1 month after surgery, and the correlation between the amount of femorotibial rotation during surgery and the MFA was statistically evaluated. RESULTS: Although the amount of tibial rotation at maximum extension was not correlated with the MFA, the amount of tibial rotation at 90 degrees of flexion after registration was positively correlated with the pre- and postoperative MFA (both p < 0.005). However, no significant relationship was observed between the amount of tibial rotation after implantation and the postoperative MFA (n.s.). CONCLUSION: The results showed that better femorotibial rotation at 90 degrees of flexion is associated with a favourable postoperative MFA, suggesting that the flexibility of the surrounding soft tissues is an important factor for obtaining a better MFA, which has important clinical relevance. Hence, further evaluation of navigation-based kinematics during TKA may provide useful information on MFA. LEVEL OF EVIDENCE: Diagnostic studies, development of diagnostic criteria in a consecutive series of patients, and a universally applied "gold" standard, Level II. PMID- 26846658 TI - Conservative and surgical management of acute isolated syndesmotic injuries: ESSKA-AFAS consensus and guidelines. AB - PURPOSE: Correct management of syndesmotic injuries is mandatory to avoid scar tissue impingement, chronic instability, heterotopic ossification, or deformity of the ankle. The aim of the present study was to perform a systematic review of the current treatments of these injuries to identify the best non-surgical and surgical management for patients with acute isolated syndesmotic injuries. METHODS: A review of the literature was performed according to the PRISMA guidelines. A comprehensive search of PubMed, Medline, CINAHL, Cochrane, Embase, and Google Scholar databases was performed using the following keywords: "ankle injury", "syndesmotic injury", "chronic", "acute", "treatment", "conservative", "non-operative" "operative", "fixation", "osteosynthesis", "screw", "synostosis", "ligamentoplasties" over the years 1962-2015. RESULTS: The literature search and cross-referencing resulted in a total of 345 references, of which 283 were rejected due to off-topic abstract and/or failure to fulfil the inclusion criteria. After reading the remaining full-text articles, we included four studies, describing non-surgical management, and only two studies investigating surgical management of acute isolated injuries. CONCLUSIONS: The ESSKA-AFAS consensus panel provided recommendations to improve the management of patients with isolated acute syndesmotic injury in clinical practice. Non-surgical management is recommended for stable ankle lesions and includes: 3-week non weight bearing, a below-the-knee cast, rest and ice, followed by proprioceptive exercises. Surgery is recommended for unstable lesions. Syndesmotic screw is recommended to achieve a temporary fixation of the mortise. Suture-button device can be considered a viable alternative to a positioning screw. Partial weight bearing is allowed 6 weeks after surgery. LEVEL OF EVIDENCE: IV. PMID- 26846659 TI - Comparison of in vivo polyethylene wear particles between mobile- and fixed bearing TKA in the same patients. AB - PURPOSE: Polyethylene wear particle generation is one of the most important factors that affects the mid- to long-term results of total knee arthroplasties (TKA). Mobile-bearing total knee prostheses were developed to reduce polyethylene wear generation. However, whether mobile-bearing prostheses actually generate fewer polyethylene wear particles than fixed-bearing prostheses remains controversial. The aim of this study was to compare, within individual patients, the in vivo polyethylene wear particles created by a newly introduced mobile bearing prosthesis in one knee and a conventional fixed-bearing prosthesis in other knee. METHODS: Eighteen patients receiving bilateral TKAs to treat osteoarthritis were included. The synovial fluid was obtained from 36 knees at an average of 3.5 years after the operation. The in vivo polyethylene wear particles were isolated from the synovial fluid using a previously validated method and examined using a scanning electron microscope and an image analyser. RESULTS: The size and shape of the polyethylene wear particles from the mobile-bearing prostheses were similar to those from the conventional fixed-bearing prostheses. Although the number of wear particles from the mobile-bearing prosthesis (1.63 * 107 counts/knee) appeared smaller than that from the fixed-bearing prosthesis (2.16 * 107 counts/knee), the difference was not statistically significant. CONCLUSIONS: The current in vivo study shows that no statistically significant differences were found between the polyethylene wear particles generated by a newly introduced mobile-bearing PS prosthesis and a conventional fixed-bearing PS prosthesis during the early clinical stage after implantation. LEVEL OF EVIDENCE: Therapeutic study, Level III. PMID- 26846660 TI - The correlation of femoral tunnel length with the height and area of the lateral wall of the femoral intercondylar notch in anatomical single-bundle ACL reconstruction. AB - PURPOSE: The purpose of this study was to reveal the correlation between femoral tunnel length and the height and area of the lateral wall of the femoral intercondylar notch in anatomical single-bundle anterior cruciate ligament (ACL) reconstruction . METHODS: Twenty-four subjects undergoing anatomical single bundle ACL reconstruction were included in this study (19 females and 5 males; average age 45.5 +/- 16.7). In the anatomical single-bundle ACL reconstruction, the femoral and tibial tunnels were created close to the anteromedial bundle insertion site. Using post-operative three-dimensional computed tomography (3D CT), an accurate lateral view of the femoral condyle was evaluated. The correlation of femoral tunnel length, which was measured intra-operatively, with the length of Blumensaat's line, and the height and area of the lateral wall of the femoral intercondylar notch was statistically analysed. Tunnel placement was also evaluated using 3D-CT (Quadrant method). RESULTS: The average femoral tunnel length was 35.3 +/- 4.9 mm. The length of Blumensaat's line, and the height and area of the lateral wall of the femoral intercondylar notch were 33.6 +/- 3.4, 22.8 +/- 2.4, and 734.6 +/- 136 mm2, respectively. Both the height and the area of the lateral wall of the femoral intercondylar notch were significantly correlated with femoral tunnel length. Femoral tunnel placement was 24.1 +/- 3.9 % in a shallow-deep direction, and 33.5 +/- 7.7 % in a high-low direction. CONCLUSION: The height and area of the lateral wall of the femoral intercondylar notch are correlated with femoral tunnel length in anatomical single-bundle ACL reconstruction. For clinical relevance, surgeons should be careful not to make the femoral tunnel too short in knees in which the femoral intercondylar notch is low in height or small in size. LEVEL OF EVIDENCE: Case-controlled study, Level III. PMID- 26846661 TI - Return to sports after arthroscopic debridement and bone marrow stimulation of osteochondral talar defects: a 5- to 24-year follow-up study. AB - PURPOSE: Osteochondral defects (OCD) often have a severe impact on the quality of life due to deep ankle pain during and after weight bearing, which prevents young patients from leading an active life. Arthroscopic debridement and bone marrow stimulation are currently the gold standard treatment. The purpose of this study was to evaluate the number of patients that resume and maintain sports to their pre-injury activity level after arthroscopic debridement and bone marrow stimulation. METHODS: This retrospective study evaluated patients treated with arthroscopic debridement and bone marrow stimulation between 1989 and 2008. All patients who were participating in sports before injury were included. The Ankle Activity Scale (AAS) was used to determine activity levels during specific time points (before injury, before operation, after operation and at the time of final follow-up). RESULTS: Ninety-three patients were included. Fifty-seven (76%) patients continued participating in sports at final follow-up. The median AAS before injury of 8 (range 3-10) significantly decreased to 4 (range 2-10) at final follow-up. CONCLUSION: It is shown that 76% of the patients were able to return to sports at long-term follow-up after arthroscopic debridement and bone marrow stimulation of talar OCDs. The activity level decreased at long-term follow-up and never reached the level of that before injury. The data of our study can be of importance to inform future patients on expectations after debridement and bone marrow stimulation of a talar OCD. LEVEL OF EVIDENCE: Retrospective case series, Level IV. PMID- 26846662 TI - Peripartum changes in social support among women with and without anxiety and depressive disorders prior to pregnancy: a prospective-longitudinal study. AB - This study aims to prospectively examine peripartum changes in social support in women with and without anxiety and depressive disorders prior to pregnancy. Data come from the Maternal Anxiety in Relation to Infant Development (MARI) Study, a prospective-longitudinal investigation among n = 306 expectant mothers. DSM-IV anxiety and depressive disorders were assessed in early pregnancy using the Composite International Diagnostic Interview for Women (CIDI-V). Social support was assessed with the Social Support Questionnaire during pregnancy as well as 4 and 16 months postpartum. Perceived social support in the total sample declined from prepartum to postpartum. Levels of prepartum and postpartum social support were lower in women with comorbid anxiety and depressive disorders compared to those with pure depressive disorder(s), pure anxiety disorder(s), or comorbid anxiety and depressive disorders prior to pregnancy. Moreover, social support more strongly declined from prepartum to postpartum in women with comorbid anxiety and depressive disorders compared to those without anxiety and depressive disorder prior to pregnancy. Findings suggest that women with a previous history of comorbid anxiety and depressive disorders are at particular risk for deficient social support during pregnancy and after delivery and might thus profit from targeted early interventions. PMID- 26846663 TI - Differences in TGF-beta1 signaling and clinicopathologic characteristics of histologic subtypes of gastric cancer. AB - BACKGROUND: Aberrant TGF-beta1 signaling is suggested to be involved in gastric carcinogenesis. However, the role of TGF-beta1 in intestinal-type [i-GC] and diffuse-type [d-GC] gastric cancer remains largely unknown. In this study, we evaluated the expression of TGF-beta1 signaling molecules and compared the clinicopathological features of i-GC and d-GC. METHODS: Patients (n=365, consecutive) who underwent curative gastrectomy for gastric adenocarcinoma in 2005 were enrolled. We performed immunohistochemical staining of TGF-beta1, TGF beta1 receptor-2 (TbetaR2), Smad4, p-ERK1/2, TGF-activated kinase (TAK)1, and p Akt in 68 paraffin-embedded tumor blocks (33 i-GC and 35 d-GC), scored the expression according to the extent of staining, and evaluated differences between the histologic subtypes. RESULTS: Patients with d-GC differed from those with i GC as follows: younger and more likely to be female; more aggressive stage; higher recurrence rate. The expression of TGF-beta1 and TbetaR2 was higher in i GC (P = 0.05 and P <0.001, respectively). The expression of Smad4, a representative molecule of the Smad-dependent pathway, was decreased in both subtypes. TAK1 and p-Akt, two major molecules involved in the Smad-independent pathway, were over-expressed (69 ~87% of cases stained), without a statistically significant difference between i-GC and d-GC. Of note, the expression of p ERK1/2, a Smad-independent pathway, was significantly increased in i-GC (P = 0.008). CONCLUSIONS: The clinicopathological characteristics vary in different histologic gastric cancer subtypes. Although TGF-beta1 signaling in gastric cancer cells appears hyper-activated in i-GC compared to d-GC, the Smad-dependent pathway seems down-regulated while the Smad-independent pathway seems up regulated in both histologic subtypes. PMID- 26846664 TI - The effects of video observation of chewing during lunch on masticatory ability, food intake, cognition, activities of daily living, depression, and quality of life in older adults with dementia: a study protocol of an adjusted randomized controlled trial. AB - BACKGROUND: Masticatory functioning alters with age. However, mastication has been found to be related to, for example, cognitive functioning, food intake, and some aspects of activities of daily living. Since cognitive functioning and activities of daily living show a decline in older adults with dementia, improving masticatory functioning may be of relevance to them. A possible way to improve mastication may be showing videos of people who are chewing. Observing chewing movements may activate the mirror neuron system, which becomes also activated during the execution of that same movement. The primary hypothesis is that the observation of chewing has a beneficial effect on masticatory functioning, or, more specifically, masticatory ability of older adults with dementia. Secondary, the intervention is hypothesized to have beneficial effects on food intake, cognition, activities of daily living, depression, and quality of life. METHODS/DESIGN: An adjusted parallel randomized controlled trial is being performed in dining rooms of residential care settings. Older adults with dementia, for whom also additional eligibility criteria apply, are randomly assigned to the experimental (videos of chewing people) or control condition (videos of nature and buildings), by drawing folded pieces of paper. Participants who are able to watch each other's videos are assigned to the same study condition. The intervention takes place during lunchtime, from Monday to Friday, for 3 months. During four moments of measurement, masticatory ability, food intake, cognitive functioning, activities of daily living, depression, and quality of life are assessed. Tests administrators blind to the group allocation administer the tests to participants. DISCUSSION: The goal of this study is to examine the effects of video observation of chewing on masticatory ability and several secondary outcome measures. In this study, the observation of chewing is added to the execution of the same action (i.e., during eating). Beneficial effects on masticatory ability, and consequently on the other outcome measures are hypothesized. The intervention may be easily integrated into daily care, and might add to the lives of the increasing number of older adults with dementia by beneficially influencing multiple daily life functions. TRIAL REGISTRATION: NTR5124. Registration date: 30 March 2015. PMID- 26846665 TI - "Helping someone with a skill sharpens it in your own mind": a mixed method study exploring health professions students experiences of Peer Assisted Learning (PAL). AB - BACKGROUND: Peer assisted learning (PAL) has been described as "the development of knowledge and skill through active help and support among status equals or matched companions". To enhance the learning experience of health professions students and improve collaborative and collegial learning, six pilot Peer Assisted Learning (PAL) projects were conducted across a health science faculty. METHODS: A responsive mixed method evaluation design was applied to explore the adequacy of the preparation for PAL, the impact PAL had on student attainment of examination, consultation, communication and feedback skills and to explore students' learning experiences through PAL. RESULTS: The 149 participants agreed the training programme was well organised, offered a safe learning environment and prepared the participant for the PAL activity. The impact of PAL included improvements in students' confidence and ability to give feedback and developed students' teaching, clinical and communication skills. Qualitative analysis revealed participants experienced deeper learning through teaching and learning from their peers, became more open to giving and receiving feedback and valued the comfortable/safe learning environment offered through PAL. CONCLUSION: Providing appropriate training in peer teaching and feedback and the schools engagement and openness to peer learning in the classroom and clinical setting enhances students' peer assisted learning experience. PMID- 26846667 TI - Classification and surgical approaches for transnasal endoscopic skull base chordoma resection: a 6-year experience with 161 cases. AB - The aim of this study is to retrospectively analyze 161 cases of surgically treated skull base chordoma, so as to summarize the clinical classification of this tumor and the surgical approaches for its treatment via transnasal endoscopic surgery. Between August 2007 and October 2013, a total of 161 patients (92 males and 69 females) undergoing surgical treatment of skull base chordoma were evaluated with regard to the clinical classification, surgical approach, and surgical efficacy. The tumor was located in the midline region of the skull base in 134 cases, and in the midline and paramedian regions in 27 cases (extensive type). Resection was performed via the transnasal endoscopic approach in 124 cases (77%), via the open cranial base approach in 11 cases (6.8%), and via staged resection combined with the transnasal endoscopic approach and open cranial base approach in 26 cases (16.2%). Total resection was achieved in 38 cases (23.6%); subtotal resection, 86 cases (53.4%); partial resection of 80-95%, 29 cases (18%); and partial resection <80%, 8 cases (5%). The clinical classification method used in this study seems suitable for selection of transnasal endoscopic surgical approach which may improve the resection degree and surgical efficacy of skull base chordoma. Gross total resection of skull base chordoma via endoscopic endonasal surgery (with addition of an open approach as needed) is a safe and viable alternative to the traditional open approach. PMID- 26846669 TI - Society for Neuroscience 2015 Satellite Symposium : Neural Mechanisms of Feeding and Swallowing. PMID- 26846666 TI - Immunotoxicity assessment of CdSe/ZnS quantum dots in macrophages, lymphocytes and BALB/c mice. AB - BACKGROUND: The toxicity of CdSe/ZnS quantum dots (QDs) in the environment and biological systems has become a major concern for the nanoparticle community. However, the potential toxicity of QDs on immune cells and its corresponding immune functions remains poorly understood. In this study, we investigated the immunotoxicity of CdSe/ZnS QDs using the in vitro in macrophages and lymphocytes and in vivo in BALB/c mice. RESULTS: Our results indicated that macrophages treated with 1.25 or 2.5 nM QDs exhibited decreased cell viability, increased levels of reactive oxygen species (ROS), elevated apoptotic events, altered phagocytic ability, and decreased release of TNF-alpha and IL-6 by upon subsequent stimulation with Lipopolysaccharide (LPS). In contrast, lymphocytes exposed to QDs exhibited enhanced cell viability, increased release of TNF-alpha and IL-6 following exposure with CpG-ODN, and decreased transformation ability treatment in response to LPS. To study the in vivo effects in mice, we showed that QDs injection did not cause significant changes to body weight, hematology, organ histology, and phagocytic function of peritoneal macrophages in QDs-treated mice. In addition, the QDs formulation accumulated in major immune organs for more than 42 days. Lymphocytes from QDs-treated mice showed reduced cell viability, changed subtype proportions, increased TNF-alpha and IL-6 release, and reduced transformation ability in response to LPS. CONCLUSIONS: Taken together, these results suggested that exposures to CdSe/ZnS QDs could suppress immune defense against foreign stimuli, which in turn could result in increased susceptibility of hosts to diseases. PMID- 26846668 TI - Remote cerebellar hemorrhage after supratentorial procedures (part 1): a systematic review. AB - A remote cerebellar hemorrhage (RCH) is a spontaneous bleeding in the posterior fossa, which may rarely occurs as a complication of supratentorial procedures, and it shows a typical bleeding pattern defined "the zebra sign." However, its pathophysiology still remains unknown. We performed a comprehensive review collecting all cases of RCH after supratentorial craniotomies reported in literature in order to identify the most frequently associated procedures and the possible risk factors. We assessed percentages of incidence and 95 % confidence intervals of all demographic, neuroradiological, and clinical features of the patients. Univariate and multivariate analyses were used to evaluate their association with outcome. We included 49 articles reporting 209 patients with a mean age of 49.09 +/- 17.07 years and a male/female ratio 130/77. A RCH was more frequently reported as a complication of supratentorial craniotomies for intracranial aneurysms, tumors debulking, and lobectomies. In the majority of cases, RCH occurrence was associated with impairment of consciousness, although some patients remained asymptomatic or showed only slight cerebellar signs. Coagulation disorders, perioperative cerebrospinal fluid drainage, hypertension, and seizures were the most frequently reported risk factors. Zebra sign was the most common bleeding pattern, being observed in about 65 % out of the cases, followed by parenchymal hematoma and mixed hemorrhage in similar percentages. A multivariate analysis showed that symptomatic onset and intake of antiplatelets/anticoagulants within a week from surgery were independent predictors of poor outcome. However, about 75 % out of patients showed a good outcome and a RCH often appeared as a benign and self-limiting condition, which usually did not require surgical treatment, but only prolonged clinical surveillance, unless in the event of the occurrence of complications. PMID- 26846671 TI - Hybrid method based on singular value decomposition and embedded zero tree wavelet technique for ECG signal compression. AB - BACKGROUND AND OBJECTIVE: In the field of biomedical, it becomes necessary to reduce data quantity due to the limitation of storage in real-time ambulatory system and telemedicine system. Research has been underway since very beginning for the development of an efficient and simple technique for longer term benefits. METHOD: This paper, presents an algorithm based on singular value decomposition (SVD), and embedded zero tree wavelet (EZW) techniques for ECG signal compression which deals with the huge data of ambulatory system. The proposed method utilizes the low rank matrix for initial compression on two dimensional (2-D) ECG data array using SVD, and then EZW is initiated for final compression. Initially, 2-D array construction has key issue for the proposed technique in pre-processing. Here, three different beat segmentation approaches have been exploited for 2-D array construction using segmented beat alignment with exploitation of beat correlation. The proposed algorithm has been tested on MIT-BIH arrhythmia record, and it was found that it is very efficient in compression of different types of ECG signal with lower signal distortion based on different fidelity assessments. RESULTS: The evaluation results illustrate that the proposed algorithm has achieved the compression ratio of 24.25:1 with excellent quality of signal reconstruction in terms of percentage-root-mean square difference (PRD) as 1.89% for ECG signal Rec. 100 and consumes only 162bps data instead of 3960bps uncompressed data. CONCLUSION: The proposed method is efficient and flexible with different types of ECG signal for compression, and controls quality of reconstruction. Simulated results are clearly illustrate the proposed method can play a big role to save the memory space of health data centres as well as save the bandwidth in telemedicine based healthcare systems. PMID- 26846670 TI - Transcriptome-enabled discovery and functional characterization of enzymes related to (2S)-pinocembrin biosynthesis from Ornithogalum caudatum and their application for metabolic engineering. AB - BACKGROUND: (2S)-Pinocembrin is a chiral flavanone with versatile pharmacological and biological activities. Its health-promoting effects have spurred on research effects on the microbial production of (2S)-pinocembrin. However, an often overlooked salient feature in the analysis of microbial (2S)-pinocembrin is its chirality. RESULTS: Here, we presented a full characterization of absolute configuration of microbial (2S)-pinocembrin from engineered Escherichia coli. Specifically, a transcriptome-wide search for genes related to (2S)-pinocembrin biosynthesis from Ornithogalum caudatum, a plant rich in flavonoids, was first performed in the present study. A total of 104,180 unigenes were finally generated with an average length of 520 bp. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping assigned 26 unigenes, representing three enzyme families of 4-coumarate:coenzyme A ligase (4CL), chalcone synthase (CHS) and chalcone isomerase(CHI), onto (2S)-pinocembrin biosynthetic pathway. A total of seven, three and one full-length candidates encoding 4CL, CHS and CHI were then verified by reverse transcription polymerase chain reaction, respectively. These candidates were screened by functional expression in E. coli individual or coupled multienzyme reaction systems based on metabolic engineering processes. Oc4CL1, OcCHS2 and OcCHI were identified to be bona fide genes encoding respective pathway enzymes of (2S)-pinocembrin biosynthesis. Then Oc4CL1, OcCHS2 and MsCHI from Medicago sativa, assembled as artificial gene clusters in different organizations, were used for fermentation production of (2S) pinocembrin in E. coli. The absolute configuration of the resulting microbial pinocembrin at C-2 was assigned to be 2S-configured by combination of retention time, UV spectrum, LC-MS, NMR, optical rotation and circular dichroism spectroscopy. Improvement of (2S)-pinocembrin titres was then achieved by optimization of gene organizations, using of codon-optimized pathway enzymes and addition of cerulenin for increasing intracellular malonyl CoA pools. Overall, the optimized strain can produce (2S)-pinocembrin of 36.92 +/- 4.1 mg/L. CONCLUSIONS: High titre of (2S)-pinocembrin can be obtained from engineered E. coli by an efficient method. The fermentative production of microbial (2S) pinocembrin in E. coli paved the way for yield improvement and further pharmacological testing. PMID- 26846673 TI - Alcohol consumption--the importance of context. PMID- 26846674 TI - Arthralgias, fatigue, paresthesias and visceral pain: can joint hypermobility solve the puzzle? A case report. AB - BACKGROUND: Joint hypermobility syndrome describes a disorder in which musculoskeletal pain occurs in a generalized joint hypermobility substrate. The clinical picture comprises variable manifestations which involve mainly but not exclusively the musculoskeletal system, and evolve over the person's lifetime. CASE PRESENTATION: Describing the case of a 20-year-old female with generalized arthro-myalgias, persistent fatigue and troublesome visceral pain, we illustrate how a frequently ignored clinical sign such as joint hypermobility can be the keystone to clarify different simultaneous symptoms. All of the patient's physical complaints had been investigated separately during her previous medical examinations, and several tests repeatedly gave negative results. The patient received different diagnoses that describe only part of her problems, such as irritable bowel syndrome for visceral pain, fibromyalgia for arthralgias or depression for fatigue. These approaches gave rise to pharmacological or physical treatments which did not improve her quality of life in any way and in some instances worsened the situation. Pronounced joint hypermobility which led the patient to flex her joints excessively, causing subluxations in several districts, was the only sign overlooked. CONCLUSION: Exploring the patient's articular features in her clinical context led us to diagnose joint hypermobility syndrome, a complex and often ignored condition. The case highlights the utility of a multidisciplinary approach and coordinated interventions to define and manage this clinical entity. PMID- 26846676 TI - Inability of the most commonly used forensic genetic markers to distinguish between samples belonging to different ethnicities of Pakistan with diverse genetic background. PMID- 26846677 TI - An appraisal of the need for infrared radiation protection in sunscreens. AB - Many sunscreens incorporate agents that are said to protect against infrared (IR) damage in the skin but we lack any real data on their benefit in the context of normal human behaviour in the sun. The object of this study was to examine typical IR exposure levels to the sun and industrial sources in order to decide whether there is a need for sunscreens to contain agents that protect against IR radiation, specifically the IR-A waveband. We reviewed claims currently made by products offering protection against IR-A and studies on the biological and clinical effects attributed to IR-A, and compared IR-A exposure levels from these studies with those typically received from the sun and from industrial sources. We found that annual levels of IR-A exposure resulting from typical behaviour in the sun are commensurate with those experienced occupationally by workers exposed to industrial sources of IR, such as steel and glass furnaces. Yet these workers appear to suffer little in the way of chronic skin damage. We conclude that there is not compelling evidence to demonstrate that observable, deleterious cutaneous effects are occurring at doses of solar IR radiation corresponding to those experienced by populations in their normal environments and for this reason we believe it is premature to incorporate IR protection into topical sunscreens and to make claims related to ageing of the skin that consumers may expect to see. PMID- 26846675 TI - Three-times-weekly, post-dialysis cefepime therapy in patients on maintenance hemodialysis: a retrospective study. AB - BACKGROUND: In hemodialysis patients, post-dialysis treatment with intravenous antibiotics permits even severe infections to be managed on an outpatient basis. Cefepime is a fourth-generation cephalosporin with a broad spectrum of action in monotherapy. We report on the pharmacokinetics of cefepime in post-dialysis therapy. METHODS: Since June 2012, twelve infections were treated with post dialysis cefepime in 9 patients on high-flux hemodialysis. The initial post dialysis dose of cefepime was approximately 15 mg/kg. The following doses were adapted according to the trough serum levels obtained before the subsequent dialysis in order to be above the EUCAST breakpoints for susceptible organisms and above the MIC90. Residual plasma concentrations were determined before (n = 30) and after (n = 17) dialysis by liquid chromatography-mass spectrometry. RESULTS: Overall, the mean +/- SD dose of cefepime was 920 +/- 270 mg (14.5 +/- 5.1 mg/kg), but it was significantly lower before the 48 h interval (775 +/- 210 mg or 12.7 +/- 4.5 mg/kg) compared to the 72 h interval (1125 +/- 225 mg or 17.2 +/- 4.9 mg/kg) (p < 0.05). The mean trough pre-dialysis concentrations were 10.7 +/- 3.9 mg/l and 11.3 +/- 5.6 mg/l at 48 and 72 h, respectively. These levels always largely exceeded the EUCAST susceptibility breakpoints for all the targeted bacteria (>1 mg/l) with the exception of Pseudomonas aeruginosa (>8 mg/l). Cefepime concentrations were higher in anuric patients compared to those with preserved diuresis (15.6 +/- 3.5 vs 9.25 +/- 3.6 mg/l; p < 0.001) and decreased on average by 81 % during dialysis (from 10.5 +/- 3.7 to 1.96 +/- 1.2 mg/l; p < 0.001). The clinical outcome of all patients was good. CONCLUSIONS: Outpatient treatment with cefepime administered post-dialysis three-times-weekly was effective and well-tolerated in our patients. According to our data, in patients infected by highly susceptible pathogens a fixed dose of cefepime of 1 g before every 48-h interval and of 1.5 g before every 72-h interval should be recommended, without need of routine monitoring of the cefepime blood levels. In patients having an infection with less susceptibles pathogens as P. aeruginosa, and particularly in those among them exhibiting residual renal function, higher initial doses are necessary (1.5 g before a 48-h interval and 2.0 g before a 72-h interval) with adaption according to the subsequent pre-dialysis trough serum levels. PMID- 26846678 TI - Synthesis and Structure of Nitride-Bridged Uranium(III) Complexes. AB - ABSTRACT: The reduction of the nitride-bridged diuranium(IV) complex Cs[{U(OSi(OtBu)3)3}2(MU-N)]affords the first example of a uranium nitride complex containing uranium in the +III oxidation state. Two nitride-bridged complexes containing the heterometallic fragments Cs2[U(III---)-N-(---U(IV)] and Cs3[U(III- -)-N-(---U(III)] have been crystallographically characterized. The presence of two or three Cs+ cations binding the nitride group is key for the isolation of these complexes. In spite of the fact that the nitride group is multiply bound to two uranium and two or three Cs+ cations, these complexes transfer the nitride group to CS2 to afford SCN(-) and uranium(IV) disulfide. PMID- 26846680 TI - Factors limiting the extent of absolute bioavailability of pradefovir in rat. AB - 1. Pradefovir was designed as an oral liver target prodrug of 9-(2 phosphonylmethoxyethyl) adenine (PMEA). Liver targeting arises through first pass hepatic metabolism by cytochrome P-450 3A4 (CYP3A4). For CYP3A4 primarily exists in intestines and liver, intestinal metabolism may impair its liver selectivity and oral bioavailability, and then impair its efficacy and safety. It was important to reveal details of the disposition of pradefovir in intestines and liver in a preclinical study. 2. The absolute bioavailability of pradefovir was 4.75% based on the intravenous and oral AUC0-24 h in rats. Pradefovir was stable in intestinal segments and microsomes. The fractions of the dose absorbed from the GI tract were 20.3% and 15.3% from intravenous and oral administration of pradefovir in rats and portal vein-cannulated rat models, respectively. The liver extraction ratio was predicted to be 49.2% from liver microsomes system, based on the monitoring substrate loss rate. Rat intestines' Ussing chamber experiment indicated that P-glycoprotein (P-gp) transporter and paracellular pathway may involve in intestinal transportation. 3. Activation of pradefovir mainly occurs in the liver. Low intestinal absorption was the main reason of low bioavailability of pradefovir in rats. The result was suggestive for the disposition of pradefovir in human intestine and liver. PMID- 26846679 TI - Factors affecting dropout in the smoking cessation outpatient clinic. AB - The objective of this study was to investigate the prevalence of discontinuation in the smoking cessation outpatient clinic (SCC) and to examine the features of noncompliance. We retrospectively included 1324 smokers into the study. Patients were divided into two groups, as those who discontinued (dropped out) follow-up (group 1) and those who stayed in follow-up (group 2). Of the total 1324 smokers, 540 (40.8%) patients were in group 1. The mean age, smoking pack-years, and Fagerstrom scores of group 1 were lower than group 2 (p = 0.001, p = 0.008, and p = 0.007, respectively). In addition, the choice of treatment was also different between groups (p < 0.001). Motivational/behavioral therapy and nicotine replacement therapy (NRT) were more common in group 1 compared with group 2. There was no difference among groups in gender, having household smokers, history of antidepressant treatment, previous quit attempts, and educational status (p > 0.05). Almost 40% of our patients did not come to their follow-up SCC visit. Younger age, lower Fagerstrom score, low amount of daily cigarette consumption, and being treated only with behavioral therapy or NRT were detected as the characteristics of the dropout group. Awareness of the characteristics of smokers who drop out of SCC programs may provide for the implementation of personalized treatment at the first appointment. PMID- 26846681 TI - Aberrantly methylated DNA regions lead to low activation of CD4+ T-cells in IgA nephropathy. AB - IgAN (IgA nephropathy) is the most common form of primary glomerulonephritis worldwide and has a strong genetic component. In this setting, DNA methylation could also be an important factor influencing this disease. We performed a genome wide screening for DNA methylation in CD4(+) T-cells from IgAN patients and found three regions aberrantly methylated influencing genes involved in the response and proliferation of CD4(+) T-cells. Two hypomethylated regions codified genes involved in TCR (T-cell receptor) signalling, TRIM27 (tripartite motif-containing 27) and DUSP3 (dual-specificity phosphatase 3), and an hypermethylated region included the VTRNA2-1 (vault RNA 2-1) non-coding RNA, also known as miR-886 precursor. We showed that the aberrant methylation influences the expression of these genes in IgAN patients. Moreover, we demonstrated that the hypermethylation of the miR-886 precursor led to a decreased CD4(+) T-cell proliferation following TCR stimulation and to the overexpression of TGFbeta (transforming growth factor beta). Finally, we found a Th1/Th2 imbalance in IgAN patients. The IL (interleukin)-2/IL-5 ratio was notably higher in IgAN patients and clearly indicated a Th1 shift. In conclusion, we identified for the first time some specific DNA regions abnormally methylated in IgAN patients that led to the reduced TCR signal strength of the CD4(+) T-cells and to their anomalous response and activation that could explain the T-helper cell imbalance. The present study reveals new molecular mechanisms underlying the abnormal CD4(+) T-cell response in IgAN patients. PMID- 26846683 TI - Role of telemedicine and mid-level dental providers in expanding dental-care access: potential application in rural Australia. AB - Despite great progress in oral health over the past three decades, the rates of caries remain high in Australia, particularly among underserved populations. The reasons for poor oral health amongst underserved populations are multiple, but rests with socio-economic determinants of health. The present review considers international workforce models that have been created to enhance the recruitment and retention of dental providers in rural areas. Several strategies have been developed to address care access problems in rural areas, including the use of telemedicine and mid-level dental providers (MLDPs). Despite ongoing opposition from dentistry organisations, the Alaska and Minnesota workforce models have proven that developing and deploying dental therapists from rural communities has the potential to address the unmet needs of underserved populations. It is more efficient and cost-effective for MLDPs to perform triage and treat simple cases and for dentists to treat complicated cases. The use of MLDPs is intended to increase the capacity of the dental workforce in areas that are too isolated to entice dentists. Telemedicine has emerged as one solution to address limited access to health care, particularly in locations where there is a lack of providers. Telemedicine not only provides access to care, but also offers support, consultations and access to continuing education for practicing dental providers in rural areas. This strategy has the potential to free up resources to increase care access and reduce oral health disparities, thereby contributing to closing the rural-urban oral health gap. PMID- 26846682 TI - Cardioprotection from emulsified isoflurane postconditioning is lost in rats with streptozotocin-induced diabetes due to the impairment of Brg1/Nrf2/STAT3 signalling. AB - Isoflurane postconditioning (IsoPostC) attenuates myocardial ischaemia/reperfusion injury (IRI). Signal transducer and activator of transcription-3 (STAT3) is critical in ischaemic postconditioning cardioprotection, which can be regulated by the Brahma-related gene (Brg1) and nuclear factor-erythroid 2-related factor 2 (Nrf2), although they are both reduced in diabetic hearts. We hypothesized that reduced Brg1/Nrf2 and STAT3 activation may jeopardize IsoPostC-mediated cardioprotection in diabetic hearts. In the present study, Langendorff-perfused, non-diabetic (control) and 8-week-old streptozotocin-induced Type 1 diabetic rat hearts were subjected to 30 min of global ischaemia and 120 min of reperfusion without or with IsoPostC, which was achieved by administering emulsified isoflurane (2.0%, v/v) in Krebs-Henseleit (KH) solution immediately at the onset of reperfusion for 10 min and switching to KH solution perfusion alone thereafter. Cultured H9C2 cells were exposed to normal glucose (NG, 5.5 mM) or high glucose (HG, 30 mM) and subjected to hypoxia/reoxygenation (HR) in the presence or absence of IsoPostC. Diabetic rats displayed larger post-ischaemic myocardial infarction and more severe haemodynamic dysfunction, associated with increased myocardial oxidative stress and reduced cardiac Brg1, Nrf2 and STAT3 phosphorylation/activation (p-STAT3), compared with controls. These changes were reversed/prevented by IsoPostC in control but not in diabetic rats. In H9C2 cells exposed to NG but not HG, IsoPostC significantly attenuated HR-induced cellular injury and superoxide anion production with increased Brg1, Nrf2 and p-STAT3. These beneficial effects of IsoPostC were abolished by Brg1, Nrf2 or STAT3 gene knockdown. Brg1 or Nrf2 gene knockdown abolished IsoPostC-induced STAT3 activation. N-acetylcysteine restored Brg1, Nrf2 and p-STAT3, and IsoPostC-induced protection in H9C2 cells exposed to HG and HR. In conclusion, IsoPostC confers cardioprotection through Brg1/Nrf2/STAT3 signalling, and impairment of this pathway may be responsible for the loss of IsoPostC cardioprotection in diabetes. PMID- 26846684 TI - Non-targeted screening for novel psychoactive substances among agitated emergency department patients. AB - CONTEXT: Novel psychoactive substances (NPS) are being created and introduced at an unprecedented rate, causing frequent, large-scale epidemics. Current identification of NPS in clinical settings in the USA is limited to the retrospective case or small cluster analysis. OBJECTIVE: The purpose of this study was to assess the utility of non-targeted comprehensive drug screening in the agitated patients in an emergency department (ED) setting. MATERIALS AND METHODS: This is a prospective, observational case series that was conducted in the ED of an urban Level I Trauma Center with an annual census of approximately 65,000 patients per year. Since it is common clinical practice at this facility for haloperidol to be used as a second-line chemical restraint when initial dose(s) of benzodiazepines are deemed insufficient, we surmised that the subset of ED patients with psychomotor agitation severe enough to receive both these pharmaceuticals would be likely users of NPS. For 1 month, biweekly pharmacy medication audits identified 49 of these patients. There were sufficient, remaining blood samples from 23 of these patients for analysis. Serum from stored blood samples was analyzed using liquid chromatography-time-of-flight mass spectrometry (LC-TOF/MS; LC 1260, TOF/MS 6230, Agilent). Retrospective chart review was done to identify patient clinical information. RESULTS: Six patient samples yielded seven different NPS: JWH-073, JWH-081, JWH-200, methylenedioxybenzylpiperazine, mephedrone, methoxetamine, and herkinorin. CONCLUSION: This study demonstrates that prospective, non-targeted NPS screening in a selected ED patient population is feasible and effective in identifying NPS. PMID- 26846685 TI - Retrieval of Embolized Transcatheter Aortic Valves in Left Ventricle Through Apical Ventriculotomy. AB - Transcatheter valve placement complicated by left ventricular embolization is often treated with sternotomy, valve removal through the aorta, and conventional aortic valve replacement. We report three cases of ventricular embolization of aortic valves during deployment. We successfully placed a second transcatheter aortic valve in the correct position and retrieved the embolized valve through an apical ventriculotomy. All patients recovered well and survived for more than one year. doi: 10.1111/jocs.12701 (J Card Surg 2016;31:203-205). PMID- 26846686 TI - Broadwick: a framework for computational epidemiology. AB - BACKGROUND: Modelling disease outbreaks often involves integrating the wealth of data that are gathered during modern outbreaks into complex mathematical or computational models of transmission. Incorporating these data into simple compartmental epidemiological models is often challenging, requiring the use of more complex but also more efficient computational models. In this paper we introduce a new framework that allows for a more systematic and user-friendly way of building and running epidemiological models that efficiently handles disease data and reduces much of the boilerplate code that usually associated to these models. We introduce the framework by developing an SIR model on a simple network as an example. RESULTS: We develop Broadwick, a modular, object-oriented epidemiological framework that efficiently handles large epidemiological datasets and provides packages for stochastic simulations, parameter inference using Approximate Bayesian Computation (ABC) and Markov Chain Monte Carlo (MCMC) methods. Each algorithm used is fully customisable with sensible defaults that are easily overridden by custom algorithms as required. CONCLUSION: Broadwick is an epidemiological modelling framework developed to increase the productivity of researchers by providing a common framework with which to develop and share complex models. It will appeal to research team leaders as it allows for models to be created prior to a disease outbreak and has the ability to handle large datasets commonly found in epidemiological modelling. PMID- 26846687 TI - Color tunable low cost transparent heat reflector using copper and titanium oxide for energy saving application. AB - Multilayer coating structure comprising a copper (Cu) layer sandwiched between titanium dioxide (TiO2) were demonstrated as a transparent heat reflecting (THR) coating on glass for energy-saving window application. The main highlight is the utilization of Cu, a low-cost material, in-lieu of silver which is widely used in current commercial heat reflecting coating on glass. Color tunable transparent heat reflecting coating was realized through the design of multilayer structure and process optimization. The impact of thermal treatment on the overall performance of sputter deposited TiO2/Cu/TiO2 multilayer thin film on glass substrate is investigated in detail. Significant enhancement of transmittance in the visible range and reflectance in the infra-red (IR) region has been observed after thermal treatment of TiO2/Cu/TiO2 multilayer thin film at 500 degrees C due to the improvement of crystal quality of TiO2. Highest visible transmittance of 90% and IR reflectance of 85% at a wavelength of 1200 nm are demonstrated for the TiO2/Cu/TiO2 multilayer thin film after annealing at 500 degrees C. Performance of TiO2/Cu/TiO2 heat reflector coating decreases after thermal treatment at 600 degrees C. The wear performance of the TiO2/Cu/TiO2 multilayer structure has been evaluated through scratch hardness test. The present work shows promising characteristics of Cu-based THR coating for energy-saving building industry. PMID- 26846688 TI - The Origins and Maintenance of Female Genital Modification across Africa : Bayesian Phylogenetic Modeling of Cultural Evolution under the Influence of Selection. AB - We present formal evolutionary models for the origins and persistence of the practice of Female Genital Modification (FGMo). We then test the implications of these models using normative cross-cultural data on FGMo in Africa and Bayesian phylogenetic methods that explicitly model adaptive evolution. Empirical evidence provides some support for the findings of our evolutionary models that the de novo origins of the FGMo practice should be associated with social stratification, and that social stratification should place selective pressures on the adoption of FGMo; these results, however, are tempered by the finding that FGMo has arisen in many cultures that have no social stratification, and that forces operating orthogonally to stratification appear to play a more important role in the cross-cultural distribution of FGMo. To explain these cases, one must consider cultural evolutionary explanations in conjunction with behavioral ecological ones. We conclude with a discussion of the implications of our study for policies designed to end the practice of FGMo. PMID- 26846689 TI - Central tarsal bone fracture in a cat. AB - Fracture of the central tarsal bone is an uncommon injury in dogs and occurs predominantly in racing Greyhounds. To the authors' knowledge, this type of fracture has not been described previously in cats. This case report describes a five-year-old Domestic Shorthair cat referred to the Centro Veterinario Luni Mare because of lameness, swelling and signs of pain in the right hindlimb caused by trauma. Clinical examination and diagnostic imaging revealed a right central tarsal bone fracture. Open reduction and internal fixation with a 2.0 mm position screw and two 0.8 mm Kirschner wires were carried out. The last follow-up examination three years postoperatively found the cat in good health with normal range of motion and function, and no signs of lameness in the right hindlimb. PMID- 26846690 TI - IL-6, IL-8, IP-10, MCP-1 and G-CSF are significantly increased in cerebrospinal fluid but not in sera of patients with central neuropsychiatric lupus erythematosus. AB - OBJECTIVE: To determine whether the intrathecal concentrations of cytokines/chemokines are associated with, or influenced by, serum concentrations in patients with central neuropsychiatric systemic lupus erythematosus (NPSLE), and to ascertain whether the increased production of cytokines/chemokines intrathecally relative to serum levels is associated with the presence of central NPSLE. METHODS: 52 SLE patients (30 with central NPSLE and 22 with non-NPSLE), for whom the CSF and serum samples were obtained at the same time, were enrolled. 27 kinds of cytokine/chemokine concentrations other than IFN-alpha in the cerebrospinal fluid (CSF) and serum samples were measured by Bio-Plex Pro Assays. IFN-alpha concentration and anti-ribosomal P protein antibody (anti-P) titres in CSF and serum samples were measured by ELISA. RESULTS: The mean concentrations of IL-6, IL-8, IP-10, MCP-1, G-CSF and GM-CSF were higher in the CSF than in the sera, respectively, while the mean concentrations of other 22 cytokines/chemokines, including RANTES and IFN-alpha, in the CSF were much lower than those in the sera, respectively. Furthermore, the concentrations of IL-6, IL 8, IP-10, MCP-1 and G-CSF in the CSF of the 30 patients with NPSLE were significantly higher than in the 22 patients with non-NPSLE (p = 6.82 * 10(-5), p = 0.00037, p = 0.0028, p = 0.00065, and p = 0.0001, respectively), while the concentration of GM-CSF in the CSF of the 30 patients with NPSLE was not significantly higher than in the 22 patients with non-NPSLE. Most importantly, the largest difference occurred in CSF IL-6 concentrations. A significant positive correlation between CSF anti-P titres and serum anti-P titres in 52 patients with SLE (r = 0.6316, p = 6.44 * 10(-6)) was found, while no significant positive correlation was observed between CSF levels and serum levels of each cytokine/chemokine in the 52 SLE patients. CONCLUSION: In central NPSLE the production of IL-6, IL-8, IP-10, MCP-1 and G-CSF might take place in the central nervous system (CNS). These increased CSF cytokines/chemokines along with anti-P might have a prerequisite role in the pathogenesis of central NPSLE. PMID- 26846691 TI - Postural Orthostatic Tachycardia Syndrome (POTS)--A novel member of the autoimmune family. AB - Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous disorder of the autonomic nervous system in which a change from the supine position to an upright position causes an abnormally large increase in heart rate or tachycardia (30 bpm within 10 min of standing or head-up tilt). This response is accompanied by a decrease in blood flow to the brain and hence a spectrum of symptoms associated with cerebral hypoperfusion. Many of these POTS-related symptoms are also observed in chronic anxiety and panic disorders, and therefore POTS is frequently under- and misdiagnosed. PMID- 26846692 TI - Impact of pulmonary disease on patient-reported outcomes and patient-performed functional testing in systemic lupus erythematosus. AB - OBJECTIVES: This study examines the effect of pulmonary disease on patient reported outcomes (PROs) and patient-performed outcome (PPO) in systemic lupus erythematosus (SLE) patients at a single tertiary referral center. METHODS: Pulmonary function tests (PFTs), chest imaging, SLE-related damage, and disease activity were examined in 110 SLE patients. Presence was noted of abnormal PFTs, pleural disease, pulmonary hypertension (PH), pulmonary infarction, interstitial lung disease (ILD), and shrinking lung syndrome (SLS). PROs included the Medical Outcome Short Form-36 Health Survey, Pittsburgh Sleep Quality Index, Fatigue Severity Scale, Borg Dyspnea Scale, patient dyspnea and cough. The PPO of interest was the six-minute walk test (6MWT). Relationships amongst PROs, 6MWT, and pulmonary disease were studied. RESULTS: Pulmonary disease was present in 62 (56%) of 110 subjects: 54 (49%) abnormal PFT, 13 (12%) pleural disease, 12 (11%) ILD, 11 (10%) SLS and five (5%) PH. Dyspnea was the only PRO found to be significantly associated with pulmonary disease (P = 0.0004). Participants with pulmonary disease compared to those without had significantly reduced distance (P = 0.00015, 95% CI for mean 39-125 m) and predicted distance (P = 0.00001, 10% 26%) on 6MWT. CONCLUSIONS: Pulmonary disease is common in SLE and adversely impacts 6MWT distance and dyspnea without apparent influence on other PROs. The 6MWT may be a promising tool in the assessment of pulmonary disease in SLE. PMID- 26846693 TI - Serological profile and clinical features of nucleolar antinuclear pattern in patients with systemic lupus erythematosus from southwestern Spain. AB - Nucleolar staining of antinuclear antibodies (ANAs) is not exclusive to patients suffering systemic sclerosis (SSc) since it can occur in other autoimmune diseases, such as systemic lupus erythematosus (SLE). The nucleolar ANA pattern presents a low incidence in patients with SLE, with less than 9% reported in some studies. The significance of nucleolar staining and antinucleolar antibodies (ANoA) in SLE is still unknown, as is its association with clinical manifestations. To address these issues, a case-control study was carried out. Twenty-eight cases of SLE with nucleolar staining were enrolled, as well as 73 controls with no nucleolar staining and different ANA patterns (homogeneous, speckled, and combined homogeneous and speckled). The homogeneous nucleolar pattern was the most frequent (27 out of 28), and in 75% was combined with other ANA patterns. The anti-double stranded DNA antibodies showed no differences between the two groups of patients, nor the auto-antibodies detected by line immunoassay (LIA). However, we have found an increased frequency of anti-PM-Scl antibodies with respect to the controls (p = 0.02), in addition to the association between Raynaud's phenomenon (RP) and anti-PM-Scl antibodies (OR = 20.72, 95% CI 1.33-323.19, p = 0.03). Moreover, the cases of SLE showed a 7.78 fold increase in the risk of developing cancer (95%, CI 1.85-32.75, p = 0.005) with respect to the control group. Taken together these findings suggest that nucleolar staining represents a comorbidity factor in patients with SLE, although its significance must still be determined. PMID- 26846694 TI - Successful treatment of systemic lupus erythematosus with subcutaneous immunoglobulin. AB - The therapeutic efficacy of high-dose intravenous immunoglobulin in systemic lupus erythematosus (SLE) patients is well established. However, side effects might limit its use and lead to the consideration of therapeutic alternatives, such as the subcutaneous formulation of immunoglobulin, which has been used in some patients with other autoimmune diseases. We report a case of SLE refractory to classical therapies. High-dose intravenous immunoglobulin was effective, but gave rise to significant side effects. The patient was successfully treated with subcutaneous human immunoglobulin, achieving and maintaining clinical and laboratory remission. A lower immunoglobulin dose was needed and no side effects were observed, compared to the intravenous administration. Subcutaneous immunoglobulin could be a better-tolerated and cost-saving therapeutic option for select SLE patients. PMID- 26846697 TI - HSP90 inhibits apoptosis and promotes growth by regulating HIF-1alpha abundance in hepatocellular carcinoma. AB - Heat shock protein (HSP)90 functions as a general oncogene by targeting several well-known oncoproteins for ubiquination and proteasomal degradation. However, the clinical significance of HSP90, as well as the mechanisms responsible for the tumor-promoting effects of HSP90 in hepatocellular carcinoma (HCC) remain unclear. In this study, HSP90 and hypoxia-inducible factor (HIF)-1alpha expression in 60 samples of HCC tissues and matched normal tumor-adjacent tissue were assessed using immunohistochemistry (IHC) or western blot analysis. Flow cytometry, BrdU cell proliferation assay, caspase-3/7 activity assay and MTT assay were used to detect the apoptosis and proliferation of the HCC cells. The regulatory effect of HSP90 on HIF-1alpha in the HCC cells was confirmed by immunofluorescence staining, western blot analysis and RT-qPCR. The interaction between HIF-1alpha and HSP90 was analyzed by co-immunoprecipitation. A subcutaneous tumor xenograft model in nude mice was established and TUNEL assay was performed to evaluate cancer cell apoptosis and growth in vivo. We found that HSP90 expression was higher in the HCC tissues than in the normal tissues and that a high HSP90 expression correlated with poor clinicopathological characteristics, including venous infiltration, an advanced TNM stage and high pathological grading. Furthermore, we confirmed that patients with a negative expression of HSP90 had an improved 3-year survival, and that HSP90 was an independent factor for predicting the prognosis of patients with HCC. We demonstrated that HSP90 promoted HCC by inhibiting apoptosis and promoting cancer cell growth. Pearson's correlation coefficient analysis indicated that HSP90 expression positively correlated with HIF-1alpha protein expression in the HCC tissues. Furthermore, we found that HSP90 regulated HIF-1alpha protein abundance by inhibiting the ubiquitination and proteasomal degradation of HIF-1alpha in HCC cells. Additionally, the upregulation of HIF-1alpha expression partially abrogated HSP90 siRNA-induced HCC cell growth arrest and apoptosis in vitro and in vivo. These results indicate that HSP90 may be used as a prognostic marker and that HIF-1alpha may be one of the potential therapeutic targets of HSP90 in HCC. PMID- 26846698 TI - Life hassles and delusional ideation: Scoping the potential role of cognitive and affective mediators. AB - OBJECTIVES: An intertemporal association between major psychological stress and subsequent delusion formation has been established by others. The current study explores (1) whether the stress from life hassles predicts delusional ideation and (2) if so, do self-criticism, self-reassurance, and positive and negative affectivity (PA and NA, respectively) mediate this link. This paper thus aimed to scope-out viable psychological processes involved in the formation of stress induced delusions. DESIGN: A cross-sectional survey using a non-clinical community sample. METHODS: Responses (N = 251) to an online community survey were tested via a nonparametric bootstrap sampling approach to examine the effects of multiple mediators. RESULTS: Self-criticism and NA appear to mediate a connection found between life hassles and delusions. A second mediation analysis found that life hassles positively predicts NA directly and indirectly (via self-criticism). NA in turn predicted delusional tendencies. Life events had direct statistical effects on delusions in all models. Neither PA nor self-reassurance mediated the stress-delusion link. CONCLUSIONS: Self-criticism and NA seem to be viable mediators worth contemplating when elaborating upon the connection between life hassles and delusions. Compared to self-criticism, NA appears to be the intervening variable most proximal to delusions and explains more variance. Even if these cross-sectional results were interpreted as causative, life hassles and delusions remained directly interconnected in all mediation models (suggesting much of the association remains unexplained). Although the results are theory consistent, investigations using longitudinal, known-group, and experimental methods are now warranted to establish causation and possible feedback loops - especially from delusion to life hassles. PRACTITIONER POINTS: Self-criticism and negative affectivity (NA) mediate the link between stressful life events and delusions suggesting they might actively elicit delusional ideation, whereas self reassurance and PA (although negatively associated with life hassles) have no unique predictive link to delusions. This study offers initial evidence that NA and self-criticism may be viable clinical intervention targets for early psychosis-sufferers under stress - especially for medically non-compliant and marginal (where drug treatment is not clinically indicated) cases. The clinical efficacy of alleviating self-criticism and/or negative emotional processes in those displaying early psychosis or at high risk appear worthy of exploration using both practice-based case studies and formal experimental research methods. PMID- 26846699 TI - Can alumina particles be formed from Al hydroxide in the circumstellar media? A first-principles chemical study. AB - AlOH has been detected in the circumstellar envelope of an oxygen-rich supergiant star (VY CMa) and is an abundant Al-containing system. Water molecules have also been detected, even in a vibrationally excited state. The coalescence of AlOH units and other processes involving AlOH could be the source of alumina-type particles. The results indicate that the formation of (AlOH)2 dimers is barrier free but (HAlO)2 systems are far more stable. The (AlOH)2 -> (HAlO)2 transformation is hindered by substantial energy barriers but is probably moderately fast at very high temperatures. Water catalysis by relay (or Grotthuss like) mechanisms substantially reduces those barriers to the point that, in the (AlOH)2.(H2O)2 system, the critical transition states lie clearly below 2AlOH + 2H2O. A surface or nucleation environment may favor the (AlOH)2 -> (HAlO)2 conversion as to be kinetically competitive with water elimination ((AlOH)2.(H2O)n -> (AlOH)2 + nH2O) in the hydrated systems. The hydrated (HAlO)2 structures can easily produce very stable hydrogenated Al2O3 and Al2O4 frames, which, to the same extent, can eliminate molecular hydrogen by exothermic processes. The remaining hydrogen atoms are exterior to the frames and perhaps could be removed by reaction with atomic hydrogen. The possible role of the coalescence of the undetected HAl(OH)2 and Al(OH)2 or AlO2H molecules is discussed. Al(OH)2 can easily be formed by reaction of AlO with a water molecule in exothermic barrier-free processes. PMID- 26846696 TI - Reactivation of telomerase in cancer. AB - Activation of telomerase is a critical step in the development of about 85 % of human cancers. Levels of Tert, which encodes the reverse transcriptase subunit of telomerase, are limiting in normal somatic cells. Tert is subjected to transcriptional, post-transcriptional and epigenetic regulation, but the precise mechanism of how telomerase is re-activated in cancer cells is poorly understood. Reactivation of the Tert promoter involves multiple changes which evolve during cancer progression including mutations and chromosomal re-arrangements. Newly described non-coding mutations in the Tert promoter region of many cancer cells (19 %) in two key positions, C250T and C228T, have added another layer of complexity to telomerase reactivation. These mutations create novel consensus sequences for transcription factors which can enhance Tert expression. In this review, we will discuss gene structure and function of Tert and provide insights into the mechanisms of Tert reactivation in cancers, highlighting the contribution of recently identified Tert promoter mutations. PMID- 26846695 TI - The epigenetic role of vitamin C in health and disease. AB - Recent advances have uncovered a previously unknown function of vitamin C in epigenetic regulation. Vitamin C exists predominantly as an ascorbate anion under physiological pH conditions. Ascorbate was discovered as a cofactor for methylcytosine dioxygenases that are responsible for DNA demethylation, and also as a likely cofactor for some JmjC domain-containing histone demethylases that catalyze histone demethylation. Variation in ascorbate bioavailability thus can influence the demethylation of both DNA and histone, further leading to different phenotypic presentations. Ascorbate deficiency can be presented systematically, spatially and temporally in different tissues at the different stages of development and aging. Here, we review how ascorbate deficiency could potentially be involved in embryonic and postnatal development, and plays a role in various diseases such as neurodegeneration and cancer through epigenetic dysregulation. PMID- 26846700 TI - Echinococcus granulosus Antigen B binds to monocytes and macrophages modulating cell response to inflammation. AB - BACKGROUND: Antigen B (EgAgB) is an abundant lipoprotein released by the larva of the cestode Echinococcus granulosus into the host tissues. Its protein moiety belongs to the cestode-specific family known as hydrophobic ligand binding protein (HLBP), and is encoded by five gene subfamilies (EgAgB8/1-EgAgB8/5). The functions of EgAgB in parasite biology remain unclear. It may play a role in the parasite's lipid metabolism since it carries host lipids that E. granulosus is unable to synthesise. On the other hand, there is evidence supporting immuno modulating activities in EgAgB, particularly on innate immune cells. Both hypothetical functions might involve EgAgB interactions with monocytes and macrophages, which have not been formally analysed yet. METHODS: EgAgB binding to monocytes and macrophages was studied by flow cytometry using inflammation recruited peritoneal cells and the THP-1 cell line. Involvement of the protein and phospholipid moieties in EgAgB binding to cells was analysed employing lipid free recombinant EgAgB subunits and phospholipase D treated-EgAgB (lacking the polar head of phospholipids). Competition binding assays with plasma lipoproteins and ligands for lipoprotein receptors were performed to gain information about the putative EgAgB receptor(s) in these cells. Arginase-I induction and PMA/LPS triggered IL-1beta, TNF-alpha and IL-10 secretion were examined to investigate the outcome of EgAgB binding on macrophage response. RESULTS: Monocytes and macrophages bound native EgAgB specifically; this binding was also found with lipid-free rEgAgB8/1 and rEgAgB8/3, but not rEgAgB8/2 subunits. EgAgB phospholipase D-treatment, but not the competition with phospholipid vesicles, caused a strong inhibition of EgAgB binding activity, suggesting an indirect contribution of phospholipids to EgAgB-cell interaction. Furthermore, competition binding assays indicated that this interaction may involve receptors with affinity for plasma lipoproteins. At functional level, the exposure of macrophages to EgAgB induced a very modest arginase-I response and inhibited PMA/LPS-mediated IL-1beta and TNF-alpha secretion in an IL-10-independent manner. CONCLUSION: EgAgB and, particularly its predominant EgAgB8/1 apolipoprotein, are potential ligands for monocyte and macrophage receptors. These receptors may also be involved in plasma lipoprotein recognition and induce an anti-inflammatory phenotype in macrophages upon recognition of EgAgB. PMID- 26846702 TI - Stereotactic radiosurgery for the treatment of mesial temporal lobe epilepsy. AB - OBJECTIVES: Stereotactic radiosurgery (RS) is a potential option for some patients with temporal lobe epilepsy (TLE). The aim of this meta-analysis was to determine the pooled seizure-free rate and the time interval to seizure cessation in patients with lesions in the mesial temporal lobe, and who were eligible for either stereotactic or gamma knife RS. MATERIALS & METHODS: We searched the Medline, Cochrane, EMBASE, and Google Scholar databases using combinations of the following terms: RS, stereotactic radiosurgery, gamma knife, and TLE. RESULTS: We screened 103 articles and selected 13 for inclusion in the meta-analysis. Significant study heterogeneity was detected; however, the included studies displayed an acceptable level of quality. We show that approximately half of the patients were seizure free over a follow-up period that ranged from 6 months to 9 years [pooled estimate: 50.9% (95% confidence interval: 0.381-0.636)], with an average of 14 months to seizure cessation [pooled estimate: 14.08 months (95% confidence interval: 11.95-12.22 months)]. Nine of 13 included studies reported data for adverse events (AEs), which included visual field deficits and headache (the two most common AEs), verbal memory impairment, psychosis, psychogenic non epileptic seizures, and dysphasia. Patients in the individual studies experienced AEs at rates that ranged from 8%, for non-epileptic seizures, to 85%, for headache. CONCLUSION: Our findings indicate that RS may have similar or slightly less efficacy in some patients compared with invasive surgery. Randomized controlled trials of both treatment regimens should be undertaken to generate an evidence base for patient decision-making. PMID- 26846701 TI - Inhibition of airway surface fluid absorption by cholinergic stimulation. AB - In upper airways airway surface liquid (ASL) depth and clearance rates are both increased by fluid secretion. Secretion is opposed by fluid absorption, mainly via the epithelial sodium channel, ENaC. In static systems, increased fluid depth activates ENaC and decreased depth inhibits it, suggesting that secretion indirectly activates ENaC to reduce ASL depth. We propose an alternate mechanism in which cholinergic input, which causes copious airway gland secretion, also inhibits ENaC-mediated absorption. The conjoint action accelerates clearance, and the increased transport of mucus out of the airways restores ASL depth while cleansing the airways. We were intrigued by early reports of cholinergic inhibition of absorption by airways in some species. To reinvestigate this phenomenon, we studied inward short-circuit currents (Isc) in tracheal mucosa from human, sheep, pig, ferret, and rabbit and in two types of cultured cells. Basal Isc was inhibited 20-70% by the ENaC inhibitor, benzamil. Long-lasting inhibition of ENaC-dependent Isc was also produced by basolateral carbachol in all preparations except rabbit and the H441 cell line. Atropine inhibition produced a slow recovery or prevented inhibition if added before carbachol. The mechanism for inhibition was not determined and is most likely multi-factorial. However, its physiological significance is expected to be increased mucus clearance rates in cholinergically stimulated airways. PMID- 26846705 TI - Acupuncture for episodic cluster headache: a trigeminal approach. AB - Following evidence that acupuncture is clinically feasible and cost-effective in the treatment of headache, the UK National Institute for Health and Care Excellence recommends acupuncture as prophylactic treatment for migraine and tension headache. There has thus been expectation that other forms of headache should benefit also. Unfortunately, acupuncture has not generally been successful for cluster headache. This may be due to acupuncturists approaching the problem as one of severe migraine. In fact, cluster headache is classed as a trigeminal autonomic cephalgia. In this case report, episodic cluster headache is treated in the same way as has been shown effective for trigeminal neuralgia. Acupuncture is applied to the contralateral side at points appropriate for stimulating branches of the trigeminal nerve. Thus, ST2 is used for the infraorbital nerve, BL2 and Yuyao for the supratrochlear and supraorbital nerves, and Taiyang for the temporal branch of the zygomatic nerve. PMID- 26846708 TI - Non-monotonic changes in critical solidification rates for stability of liquid solid interfaces with static magnetic fields. AB - We report the magnetic field dependence of the critical solidification rate for the stability of liquid-solid interfaces. For a certain temperature gradient, the critical solidification rate first increases, then decreases, and subsequently increases with increasing magnetic field. The effect of the magnetic field on the critical solidification rate is more pronounced at low than at high temperature gradients. The numerical simulations show that the magnetic-field dependent changes of convection velocity and contour at the interface agree with the experimental results. The convection velocity first increases, then decreases, and finally increases again with increasing the magnetic field intensity. The variation of the convection contour at the interface first decreases, then increases slightly, and finally increases remarkably with increasing the magnetic field intensity. Thermoelectromagnetic convection (TEMC) plays the role of micro stirring the melt and is responsible for the increase of interface stability within the initially increasing range of magnetic field intensity. The weak and significant extents of the magneto-hydrodynamic damping (MHD)-dependent solute build-up at the interface front result, respectively, in the gradual decrease and increase of interfacial stability with increasing the magnetic field intensity. The variation of the liquid-side concentration at the liquid-solid interface with the magnetic field supports the proposed mechanism. PMID- 26846703 TI - Toxin MqsR cleaves single-stranded mRNA with various 5' ends. AB - Toxin/antitoxin (TA) systems are the means by which bacterial cells become persistent; that is, those cells that are tolerant to multiple environmental stresses such as antibiotics by becoming metabolically dormant. These persister cells are responsible for recalcitrant infections. Once toxins are activated by the inactivation of antitoxins (e.g., stress-triggered Lon degradation of the antitoxin), many toxins reduce metabolism by inhibiting translation (e.g., cleaving mRNA, reducing ATP). The MqsR/MqsA TA system of Escherichia coli cleaves mRNA to help the cell withstand oxidative and bile acid stress. Here, we investigated the role of secondary structure and 5' mRNA processing on MqsR degradation of mRNA and found that MqsR cleaves only single-stranded RNA at 5' GCU sites and that MqsR is equally active against RNA with 5'-triphosphate, 5' monophosphate, and 5'-hydroxyl groups. PMID- 26846709 TI - Bioinformatics Analysis of NBS-LRR Encoding Resistance Genes in Setaria italica. AB - In plants, resistance (R) genes are involved in pathogen recognition and subsequent activation of innate immune responses. The nucleotide-binding site leucine-rich repeat (NBS-LRR) genes family forms the largest R-gene family among plant genomes and play an important role in plant disease resistance. In this paper, comprehensive analysis of NBS-encoding genes is performed in the whole Setaria italica genome. A total of 96 NBS-LRR genes are identified, and comprehensive overview of the NBS-LRR genes is undertaken, including phylogenetic analysis, chromosome locations, conserved motifs of proteins, and gene expression. Based on the domain, these genes are divided into two groups and distributed in all Setaria italica chromosomes. Most NBS-LRR genes are located at the distal tip of the long arms of the chromosomes. Setaria italica NBS-LRR proteins share at least one nucleotide-biding domain and one leucine-rich repeat domain. Our results also show the duplication of NBS-LRR genes in Setaria italica is related to their gene structure. PMID- 26846710 TI - Evaluation of BP-ONJ in osteopenic and healthy sheep: comparing ZTE-MRI with uCT. AB - OBJECTIVES: Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is a side effect of antiresorptive treatment that is increasingly prescribed for patients with osteoporosis or malignant diseases with bone metastases. Surgical treatment of BP-ONJ requires adequate pre-operative imaging. To date, CT is the imaging standard in clinical routine; however, defining the extent of the pathological area is difficult and soft tissues are poorly displayed. MRI with zero echo time (ZTE-MRI) to display hard tissues enables a precise display of calcified structures and soft tissues for the delineation of bone necrosis and soft-tissue reactions. METHODS: BP-ONJ was induced in eight sheep by extraction of two premolars in the left mandible and zoledronate (ZOL) administration. Eight sheep without ZOL administration served as the control group. Four sheep of each main group underwent osteopenia induction via ovariectomy, glucocorticoid administration and a calcium-free diet. After sacrifice, the area of tooth extraction was harvested and scanned with micro-CT (uCT) and ZTE-MRI. Two trained dentists analyzed digital imaging and communications in medicine data sets using three-dimensional imaging software. The periosteal reaction and the remaining extraction sockets were measured. RESULTS: BP-ONJ was evident, and the remaining extraction sockets were observed in all animals treated with ZOL. Periosteal reactions were more pronounced in animals treated with ZOL, and they appeared broader in ZTE-MRI. CONCLUSIONS: BP-ONJ lesions in the sheep mandible can be detected using uCT and ZTE-MRI. Although illustration of sequester was more consistent using the uCT, ZTE-MRI was advantageous in evaluation of periosteal reaction. PMID- 26846711 TI - Quantitative dynamic contrast-enhanced and diffusion-weighted MRI for differentiation between nasopharyngeal carcinoma and lymphoma at the primary site. AB - OBJECTIVES: To investigate the value of quantitative dynamic contrast-enhanced MRI (QDCE-MRI) and diffusion-weighted MRI (DW-MRI) in differentiating nasopharyngeal carcinoma (NPC) from lymphoma. METHODS: We retrospectively analysed the data from 102 patients (82 with NPC and 20 with lymphoma) who underwent pre-treatment QDCE-MRI and DW-MRI on a 1.5-T MR unit. QDEC-MRI parameters [influx transfer constant (K(trans)), efflux rate constant (Kep), fractional volume of extravascular extracellular space (Ve) and fractional volume of plasma (fPV)] based on pharmacokinetic model and apparent diffusion coefficient (ADC) were compared between the two nasopharyngeal malignancies. RESULTS: The K(trans), Kep, Ve, fPV and ADC values (mean +/- standard deviation) for NPC were 0.366 +/- 0.155 min(-1), 1.353 +/- 0.468 min(-1), 0.292 +/- 0.117, 0.027 +/- 0.024 and 0.981 +/- 0.184 * 10(-3) mm(2) s(-1), respectively. The K(trans), Kep, Ve, fPV and ADC values (mean +/- standard deviation) for lymphoma were 0.212 +/- 0.059 min(-1), 1.073 +/- 0.238 min(-1), 0.213 +/- 0.104, 0.008 +/- 0.007 and 0.760 +/- 0.182 * 10(-3) mm(2) s(-1), respectively. Optimal cut-off values (area under the curve, sensitivity, specificity) for distinguishing the two tumours were as follows: K(trans) = 0.262 min(-1) (0.866, 80.49%, 85.00%), Kep = 1.401 min(-1) (0.681, 43.90%, 100.00%), Ve = 0.211 (0.784, 76.83%, 85.00%), fPV = 0.012 (0.779, 60.98%, 85.00%), ADC = 0.761 * 10(-3) mm(2) s(-1) (0.781, 93.90%, 55.00%). CONCLUSIONS: QDCE-MRI together with DW-MRI is useful for differentiation between NPC and lymphoma. PMID- 26846712 TI - Dynamic contrast-enhanced MR in the diagnosis of lympho-associated benign and malignant lesions in the parotid gland. AB - OBJECTIVE: The aim of this study was to determine if dynamic contrast-enhanced (DCE)-MRI can differentiate mucosa-associated lymphoid tissue (MALT) lymphoma from benign lymphoepithelial lesion (BLEL) in the parotid gland. METHODS: 25 patients with tumour-like BLEL and 20 patients with MALT lymphoma in the parotid gland confirmed by pathology were examined pre-operatively using routine MR series and DCE-MRI with a 1.5-T MR unit. The time to peak (TTP), time to start (TTS), SIstart, SImax and SIending were measured and the initial slope of increase (ISI) and relative washout ratio (RWO) were calculated separately from the time-intensity curve (TIC), and the types of TIC were analysed. RESULTS: There were significant differences in the TTP and ISI between the two lesions (p < 0.001). The sensitivity, specificity and accuracy of TTP were all more than 90%. TICs were divided into three types according to the threshold of TTP and ISI: tumour-like BLEL: gradual type (Type II) and late increase type (Type III); MALT lymphoma: rapid increase and gradual type (Type I). CONCLUSIONS: DCE-MRI contributed greatly to the differential diagnosis between tumour-like BLEL and MALT lymphoma in the parotid gland. PMID- 26846713 TI - The hitchhiker's guide to Europe: the infection dynamics of an ongoing Wolbachia invasion and mitochondrial selective sweep in Rhagoletis cerasi. AB - Wolbachia is a maternally inherited and ubiquitous endosymbiont of insects. It can hijack host reproduction by manipulations such as cytoplasmic incompatibility (CI) to enhance vertical transmission. Horizontal transmission of Wolbachia can also result in the colonization of new mitochondrial lineages. In this study, we present a 15-year-long survey of Wolbachia in the cherry fruit fly Rhagoletis cerasi across Europe and the spatiotemporal distribution of two prevalent strains, wCer1 and wCer2, and associated mitochondrial haplotypes in Germany. Across most of Europe, populations consisted of either 100% singly (wCer1) infected individuals with haplotype HT1, or 100% doubly (wCer1&2) infected individuals with haplotype HT2, differentiated only by a single nucleotide polymorphism. In central Germany, singly infected populations were surrounded by transitional populations, consisting of both singly and doubly infected individuals, sandwiched between populations fixed for wCer1&2. Populations with fixed infection status showed perfect association of infection and mitochondria, suggesting a recent CI-driven selective sweep of wCer2 linked with HT2. Spatial analysis revealed a range expansion for wCer2 and a large transition zone in which wCer2 splashes appeared to coalesce into doubly infected populations. Unexpectedly, the transition zone contained a large proportion (22%) of wCer1&2 individuals with HT1, suggesting frequent intraspecific horizontal transmission. However, this horizontal transmission did not break the strict association between infection types and haplotypes in populations outside the transition zone, suggesting that this horizontally acquired Wolbachia infection may be transient. Our study provides new insights into the rarely studied Wolbachia invasion dynamics in field populations. PMID- 26846714 TI - Wnt3a suppresses Pseudomonas aeruginosa-induced inflammation and promotes bacterial killing in macrophages. AB - Pseudomonas aeruginosa (PA) is a common Gram-negative bacterium and can cause serious infections, including hospital-acquired pneumonia, suppurative bacterial keratitis and acute burn wound infection. The pathogenesis of PA infections is closely associated with excessive inflammatory responses and bacterial virulence factors. Wingless-type MMTV integration site family, member 3A (Wnt3a), an upstream mediator in the canonical Wnt signaling pathway, has been implicated as a regulator of inflammation. However, its role in PA-induced inflammation and bacterial clearance remains unknown. In the present study, the efficacy of Wnt3a conditioned media (Wnt3a-CM) was assessed using western blotting and immunofluorescence, which showed that beta-catenin, a downstream molecule of Wnt3a, was upregulated and translocated to the nucleus following exposure to 50% Wnt3a-CM for 6 h. To explore the role of Wnt3a in PA-induced inflammation, the mRNA levels of pro-inflammatory cytokines and apoptosis in macrophages were measured using reverse transcription-quantitative polymerase chain reaction and flow cytometry, respectively. This indicated that Wnt3a suppressed inflammation by reducing the production of pro-inflammatory cytokines and by promoting apoptosis in macrophages. Furthermore, the mechanism of macrophage-mediated bacterial killing was investigated, and the results indicated that Wnt3a enhanced macrophage-mediated intracellular bacterial killing via the induction of the production of cathelicidin-related antimicrobial peptide and beta-defensins 1. Taken together, the current study explored the role of Wnt3a in inflammation and bacterial invasion, which may provide an improved understanding of host resistance to PA infection. PMID- 26846715 TI - Effects of titanium dioxide nanoparticle exposure in Mytilus galloprovincialis gills and digestive gland. AB - Despite the wide use of nanoscale materials in several fields, some aspects of the nanoparticle behavior have to be still investigated. In this work, we faced the aspect of environmental effects of increasing concentrations of TiO2NPs using the Mytilus galloprovincialis as an animal model and carrying out a multidisciplinary approach to better explain the results. Bioaccumulation suggested that the gills and digestive gland are the most sensitive organs to TiO2NP exposure. Histological observations have evidenced an altered tissue organization and a consistent infiltration of hemocytes, as a consequence of the immune system activation, even though an increase in lipid peroxidation is uncertain and DNA damage became relevant only at high exposure dose (10 mg/L) or for longer exposure time (96 h). However, the over expression of SOD1 mRNA strengthen the concept that the toxicity of TiO2NPs could occur indirectly by ROS production. TEM analysis showed the presence of multilamellar bodies, RER fragmentation, and cytoplasmic vacuolization within relevant presence of dense granules, residual bodies, and lipid inclusions. These findings support the evidence of an initial inflammatory response by the cells of the target organs leading to apoptosis. In conclusion, we can state that certainly the exposure to TiO2NPs has affected our animal model from cellular to molecular levels. Interestingly, the same responses are caused by lower TiO2NP concentration and longer exposure time as well as higher doses and shorter exposure. We do not know if some of the conditions detected are reversible, then further studies are required to clarify this aspect. PMID- 26846716 TI - Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy. AB - To investigate how organic anion transporter (OAT)-1 is involved in uric acid nephropathy (UAN), a rat model for UAN was established and the serum uric acid, blood urea nitrogen and serum creatinine levels were all measured, and observed to be increased. It was additionally identified that in UAN rats the surface OAT1 expression levels were reduced. By treating HEK cells with monosodium urate (MSU) crystals, it was observed that the cells exhibited a reduction in OAT1 levels. Furthermore, MSU crystals were observed to recruit Ras homolog family member A (RhoA), a small guanosine triphosphatase, to the membrane and activate it. Following RhoA activation, the OAT1 internalization rate was identified to be increased. The dominant-negative RhoA N19 mutation was able to block MSU-induced OAT1 internalization, indicating that the process was RhoA-dependent. Finally, the results indicated that folic acid, a daily nutritional supplement, was capable of rescuing MSU-induced nephropathy and OAT1 internalization. These observations indicated that uric acid crystals were able to reduce the OAT1 membrane distribution through activating RhoA, and that folic acid was capable of preventing MSU-induced OAT1 relocation by inhibiting the RhoA signaling pathway. PMID- 26846718 TI - The outcome of Chronic lymphocytic leukaemia patients with 97% IGHV gene identity to germline is distinct from cases with <97% identity and similar to those with 98% identity. AB - IGHV gene mutational status has prognostic significance in chronic lymphocytic leukaemia (CLL) but the percentage of mutations that correlates best with clinical outcome remains controversial. We initially studied 558 patients from diagnosis and found significant differences in median time to first treatment (TTFT) among Stage A patients and in overall survival (OS) for the whole cohort, between cases with <97% and 97-98.99% identity and between cases with 97-98.99% and >=99% identity, when cases from the IGHV3-21 Stereotype Subset #2 were excluded. A significant difference in progression-free survival (PFS) and OS between those with <97% and 97-98.99% identity, but not between those with 97 98.99% and >=99% identity was also observed in a validation cohort comprising 460 patients in the UK CLL4 trial. Cox Regression analyses in the Stage A cohort revealed that a model which incorporated <97%, 97-98.99% and >=99% identity as subgroups, was a better predictor of TTFT in CLL than using the 98% cut-off. Multivariate analysis selected the three mutational subgroups as independent predictors of TTFT in Stage A patients, and of OS in the diagnostic cohort. This study highlights that cases with 97% identity should not be considered to have the same prognosis as other cases with mutated IGHV genes defined as <98% identity to germline. PMID- 26846717 TI - Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection. AB - Tetherin/BST-2 is a host restriction factor that inhibits retrovirus release from infected cells in vitro by tethering nascent virions to the plasma membrane. However, contradictory data exists on whether Tetherin inhibits acute retrovirus infection in vivo. Previously, we reported that Tetherin-mediated inhibition of Friend retrovirus (FV) replication at 2 weeks post-infection correlated with stronger natural killer, CD4+ T and CD8+ T cell responses. Here, we further investigated the role of Tetherin in counteracting retrovirus replication in vivo. FV infection levels were similar between wild-type (WT) and Tetherin KO mice at 3 to 7 days post-infection despite removal of a potent restriction factor, Apobec3/Rfv3. However, during this phase of acute infection, Tetherin enhanced myeloid dendritic cell (DC) function. DCs from infected, but not uninfected, WT mice expressed significantly higher MHC class II and the co stimulatory molecule CD80 compared to Tetherin KO DCs. Tetherin-associated DC activation during acute FV infection correlated with stronger NK cell responses. Furthermore, Tetherin+ DCs from FV-infected mice more strongly stimulated FV specific CD4+ T cells ex vivo compared to Tetherin KO DCs. The results link the antiretroviral and immunomodulatory activity of Tetherin in vivo to improved DC activation and MHC class II antigen presentation. PMID- 26846719 TI - Methamphetamine-, d-Amphetamine-, and p-Chloroamphetamine-Induced Neurotoxicity Differentially Effect Impulsive Responding on the Stop-Signal Task in Rats. AB - Abused amphetamines, such as d-amphetamine (AMPH) and methamphetamine (METH), are highly addictive and destructive to health and productive lifestyles. The abuse of these drugs is associated with impulsive behavior, which is likely to contribute to addiction. The amphetamines also differentially damage dopamine (DA) and serotonin (5-HT) systems, which regulate impulsive behavior; therefore, exposure to these drugs may differentially alter impulsive behavior to effect the progression of addiction. We examined the impact of neurotoxicity induced by three amphetamines on impulsive action using a stop-signal task in rats. Animals were rewarded with a food pellet after lever pressing (i.e., a go trial), unless an auditory cue was presented and withholding lever press gained reward (i.e., a stop trial). Animals were trained on the task and then exposed to a neurotoxic regimen of either AMPH, p-chloroamphetamine (PCA), or METH. These regimens preferentially reduced DA transporter levels in striatum, 5-HT transporter levels in prefrontal cortex, or both, respectively. Assessment of performance on the stop-signal task beginning 1 week after the treatment revealed that AMPH produced a deficit in go-trial performance, whereas PCA did not alter performance on either trial type. In contrast, METH produced a deficit in stop-trial performance (i.e., impulsive action) but not go-trial performance. These findings suggest that the different neurotoxic consequences of substituted amphetamines are associated with different effects on inhibitory control over behavior. Thus, the course of addiction and maladaptive behavior resulting from exposure to these substances is likely to differ. PMID- 26846720 TI - West Nile virus-neutralizing antibodies in wild birds from southern Spain. AB - West Nile virus (WNV) is an emerging vector-borne arbovirus with a zoonotic life cycle whose main reservoir hosts are birds. In humans and horses, WNV infections rarely result in clinical disease but on occasions - depending on factors such as climatic conditions, insect communities and background immunity levels in local populations - they can lead to outbreaks that threaten public and animal health. We tested for the presence of WNV antibodies in 149 birds belonging to 32 different species. Samples were first tested using a bird-specific ELISA kit and then both positive and doubtful results were confirmed by neutralization tests using WNV and Usutu virus. WNV antibodies were confirmed in a resident Sylvia melanocephala juvenile, supporting the idea of local transmission of WNV in southern Spain in 2013. In addition, the serum from an adult blackbird (Turdus merula) showed neutralization of both WNV and Usutu virus. We discuss our results in light of the occurrence of WNV on horse farms in southern Spain in 2013. PMID- 26846721 TI - The angiogenic variation of skeletal site-specific human BMSCs from same alveolar cleft patients: a comparative study. AB - Tissue engineering strategies hold great potential for alveolar cleft reconstruction. Bone marrow stromal cells (BMSCs) from iliac crest and craniofacial regions are candidate seeding cells with site-specific characteristics and bone-repairing properties. Craniofacial BMSCs seem to possess stronger multipotency and osteogenic capabilities than BMSCs isolated from iliac crest. However, the angiogenic capabilities of these two type cell is rarely reported. We obtained human BMSCs (hBMSCs) of maxilla (M-hBMSCs) and iliac crest (I-hBMSCs) from same alveolar cleft patients to investigate the agiogenic variations using co-culture system with human umbilical vein endothelial cells (HUVECs). From in vitro comparison, M-hBMSCs allowed HUVECs to form more tube like structures and sprouting angiogenesis by tube formation assays and 3D fibrin vasculogenic assay, respectively. By transplantation in vivo, M-hBMSCs enhanced larger size vessel like structures distributed the entire implants compared with I-hBMSCs. Western blotting was used to assess the angiogenesis related factors including hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). The results showed a significant higher expression of bFGF protein in M-hBMSCs and HUVECs co-culture system both in vitro and in vivo. As bFGF could promote migration and proliferation of endothelial cells, scratch wound healing and transwell migration assays were performed as well as MTT assays and cell cycle analysis. The data suggested the effect of M-hBMSCs on HUVECs was stronger than I-hBMSCs. Taken together, these results indicated that craniofacial BMSCs seemed to have greater angiogenesis capability than iliac crest BMSCs and this might be associated with the different levels of bFGF protein expression in co-culture system. PMID- 26846723 TI - Quantitative measurements of GDF-8 using immunoaffinity LC-MS/MS. AB - PURPOSE: Growth and differentiation factor 8 (GDF-8) is a negative regulator of skeletal muscle mass and targeted by inhibitors to treat diseases associated with muscle loss. In order to enable clinical and translational investigations of GDF 8 inhibitors, specific and sensitive measurements of GDF-8 are necessary. EXPERIMENTAL DESIGN: An immunoaffinity LC-MS/MS assay for quantification of GDF-8 in serum was developed, qualified and implemented. The workflow includes offline enrichment of GDF-8 using an anti-GDF-8 antibody, followed by isolation using magnetic beads, trypsin digestion, and quantification using 2D nanoflow LC-MS/MS. RESULTS: This assay was qualified in human serum with a lower LOQ of 1.0 ng/mL based on the intact protein. GDF-8 was quantified in serum from juvenile and adult humans as well as mouse, rat, and cynomolgus monkey. Additionally, the assay was utilized to demonstrate an increase of total GDF-8 in serum following administration of an anti-GDF-8 monoclonal antibody therapeutic in cynomolgus monkeys. CONCLUSIONS AND CLINICAL RELEVANCE: A specific and sensitive method was developed for the measurement of GDF-8 in juvenile and adult serum samples as well as preclinical species. The confident quantification of GDF-8 now enables a greater understanding of any association between changes GDF-8 levels and muscle mass. PMID- 26846724 TI - Seed handling by primary frugivores differentially influence post-dispersal seed removal of Chinese yew by ground-dwelling animals. AB - Seed handling by primary frugivores can influence secondary dispersal and/or predation of post-dispersal seeds by attracting different guilds of ground dwelling animals. Many studies have focused on seeds embedded in feces of mammals or birds; however, less is known about how ground-dwelling animals treat seeds regurgitated by birds (without pulp and not embedded in feces). To compare the effect of differential seed handling by primary dispersers on secondary seed removal of Chinese yew (Taxus chinensis var. mairei), we conducted a series of exclosure experiments to determine the relative impact of animals on the removal of defecated seeds (handled by masked palm civet), regurgitated seeds (handled by birds) and intact fruits. All types of yew seeds were consistently removed at a higher rate by rodents than by ants. Regurgitated seeds had the highest removal percentage and were only removed by rodents. These seeds were probably eaten in situ without being secondarily dispersed. Defecated seeds were removed by both rodents and ants; only ants might act as secondary dispersers of defecated seeds, whereas rodents ate most of them. We inferred that seeds regurgitated by birds were subjected to the highest rates of predation, whereas those dispersed in the feces of masked palm civets probably had a higher likelihood of secondary dispersal. Seeds from feces attracted ants, which were likely to transport seeds and potentially provided a means by which the seeds could escape predation by rodents. Our study highlighted that primary dispersal by birds might not always facilitate secondary dispersal and establishment of plant populations. PMID- 26846722 TI - A genome-wide association study of fetal response to type 2 porcine reproductive and respiratory syndrome virus challenge. AB - Control of porcine reproductive and respiratory syndrome (PRRS) is economically important for the swine industry worldwide. As current PRRS vaccines do not completely protect against heterologous challenge, alternative means of control, including enhanced genetic resilience, are needed. For reproductive PRRS, the genetic basis of fetal response to PRRS virus (PRRSV) infection is poorly understood. Genome-wide association studies (GWAS) were done here using data from 928 fetuses from pregnant gilts experimentally challenged with type 2 PRRSV. Fetuses were assessed for viral load in thymus (VLT), viral load in endometrium (VLE), fetal death (FD) and fetal viability (FV), and genotyped at a medium density. Collectively, 21 candidate genomic regions were found associated with these traits, seven of which overlap with previously reported QTLs for pig health and reproduction. A comparison with ongoing and related transcriptomic analyses of fetal response to PRRSV infection found differentially expressed genes within 18 candidate regions. Some of these genes have immune system functions, and have been reported to contribute to host response to PRRSV infection. The results provide new evidence about the genetic basis of fetal response to PRRSV challenge, and may ultimately lead to alternative control strategies to reduce the impact of reproductive PRRS. PMID- 26846725 TI - Identification of human viral protein-derived ligands recognized by individual MHCI-restricted T-cell receptors. AB - Evidence indicates that autoimmunity can be triggered by virus-specific CD8(+) T cells that crossreact with self-derived peptide epitopes presented on the cell surface by major histocompatibility complex class I (MHCI) molecules. Identification of the associated viral pathogens is challenging because individual T-cell receptors can potentially recognize up to a million different peptides. Here, we generate peptide length-matched combinatorial peptide library (CPL) scan data for a panel of virus-specific CD8(+) T-cell clones spanning different restriction elements and a range of epitope lengths. CPL scan data drove a protein database search limited to viruses that infect humans. Peptide sequences were ranked in order of likelihood of recognition. For all anti-viral CD8(+) T-cell clones examined in this study, the index peptide was either the top ranked sequence or ranked as one of the most likely sequences to be recognized. Thus, we demonstrate that anti-viral CD8(+) T-cell clones are highly focused on their index peptide sequence and that 'CPL-driven database searching' can be used to identify the inciting virus-derived epitope for a given CD8(+) T-cell clone. Moreover, to augment access to CPL-driven database searching, we have created a publicly accessible webtool. Application of these methodologies in the clinical setting may clarify the role of viral pathogens in the etiology of autoimmune diseases. PMID- 26846727 TI - Failed fiberoptic intubation in a child with epidermolysis bullosa, rescued with combined use of the Glidescope(r). AB - We present the case of a 13-year-old male with epidermolysis bullosa having an elective syndactyly release. These patients present significant challenges to the anaesthetist; extreme care in patient handling is required. Recurrent and pronounced scarring of intra-oral, pharyngeal and laryngeal tissues is a feature, resulting in a difficult airway. Following a failed intubation using a fibreoptic bronchoscope, we describe a combined technique by adding in the Glidescope((r)). This proved immediately successful. Its utilisation has been reported in adults. We wish to present our experience in the paediatric population, and this is the first report in a child with epidermiolysis bullosa. PMID- 26846726 TI - Antibody acquisition models: A new tool for serological surveillance of malaria transmission intensity. AB - Serology has become an increasingly important tool for the surveillance of a wide range of infectious diseases. It has been particularly useful to monitor malaria transmission in elimination settings where existing metrics such as parasite prevalence and incidence of clinical cases are less sensitive. Seroconversion rates, based on antibody prevalence to Plasmodium falciparum asexual blood-stage antigens, provide estimates of transmission intensity that correlate with entomological inoculation rates but lack precision in settings where seroprevalence is still high. Here we present a new and widely applicable method, based on cross-sectional data on individual antibody levels. We evaluate its use as a sero-surveillance tool in a Tanzanian setting with declining malaria prevalence. We find that the newly developed mathematical models produce more precise estimates of transmission patterns, are robust in high transmission settings and when sample sizes are small, and provide a powerful tool for serological evaluation of malaria transmission intensity. PMID- 26846728 TI - Therapeutic Advances in HCV Genotype 1 Infection: Insights from the Society of Infectious Diseases Pharmacists. AB - Hepatitis C virus (HCV) is the most common blood-borne infection in the United States. The high morbidity and mortality due to untreated infection have prompted updated screening recommendations that now include one-time HCV screening for all patients born between 1945 and 1965, in addition to risk factor-based screening. Current guidelines recommend treatment for all patients with chronic HCV. Treatment for HCV genotype 1 has evolved dramatically since the approval of the direct-acting antivirals. The approval of ledipasvir-sofosbuvir, ombitasvir paritaprevir-ritonavir and dasabuvir, and simeprevir with sofosbuvir has dramatically altered the treatment landscape. High sustained virologic response (SVR) rates favor treatment, yet access to care poses a challenge for patients and providers. Current and emerging data with new therapies indicate high SVR rates in treatment-naive and treatment-experienced patients, including patients with cirrhosis and in other special populations. Additional data suggest the addition of ribavirin can decrease treatment duration without compromising SVR rates. Resistance is an increasing area of interest in HCV, with baseline mutations identified and the potential for the development of resistance associate variants in patients undergoing treatment. Due to the rapid evolution of HCV treatment, pharmacists should address challenges and play an integral role in agent selection, dosing, drug interaction screening, adverse effect monitoring, and the coordination of treatment. Clinical application of the latest information will reduce patient risk and improve outcomes. PMID- 26846729 TI - Chloroplast Phylogenomic Inference of Green Algae Relationships. AB - The green algal phylum Chlorophyta has six diverse classes, but the phylogenetic relationship of the classes within Chlorophyta remains uncertain. In order to better understand the ancient Chlorophyta evolution, we have applied a site pattern sorting method to study compositional heterogeneity and the model fit in the green algal chloroplast genomic data. We show that the fastest-evolving sites are significantly correlated with among-site compositional heterogeneity, and these sites have a much poorer fit to the evolutionary model. Our phylogenomic analyses suggest that the class Chlorophyceae is a monophyletic group, and the classes Ulvophyceae, Trebouxiophyceae and Prasinophyceae are non-monophyletic groups. Our proposed phylogenetic tree of Chlorophyta will offer new insights to investigate ancient green algae evolution, and our analytical framework will provide a useful approach for evaluating and mitigating the potential errors of phylogenomic inferences. PMID- 26846730 TI - The lack of antiepileptic drugs and worsening of seizures among physically handicapped patients with epilepsy during the Great East Japan Earthquake. AB - BACKGROUND: Takuto Rehabilitation Center for Children is located in Sendai, the capital of the Miyagi prefecture, and faces the Pacific Ocean. The tsunami caused by the Great East Japan Earthquake resulted in tremendous damage to this region. Many physically handicapped patients with epilepsy who are treated at our hospital could not obtain medicine. We surveyed patients with epilepsy, using a questionnaire to identify the problems during the acute phase of the Great East Japan Earthquake. METHODS: After the earthquake, we mailed questionnaires to physically handicapped patients with epilepsy who are treated and prescribed medications at our hospital, or to their parents. RESULTS: A total of 161 respondents completed the questionnaire. Overall, 68.4% of patients had seven days or less of stockpiled medication when the earthquake initially struck, and 28.6% of patients had no medication or almost no medication during the acute phase after the earthquake. Six patients were forced to stop taking their medication and nine patients experienced a worsening of seizures. Most (93.6%) patients stated they require a stockpile of medication for more than seven days: 20months after the earthquake, 76.9% patients a supply of drugs for more than seven days. CONCLUSIONS: We suggest that physically handicapped patients with epilepsy are recommended to prepare for natural disasters by stockpiling additional medication. Even if the stock of antiepileptic drugs is sufficient, stress could cause worsening of seizures. Specialized support is required after a disaster among physically handicapped patients with epilepsy. PMID- 26846731 TI - A girl with infantile neuronal ceroid lipofuscinosis caused by novel PPT1 mutation and paternal uniparental isodisomy of chromosome 1. AB - BACKGROUND: Infantile neuronal ceroid lipofuscinosis (INCL) is an autosomal recessive disorder starting in infancy as early as 12-month-old, caused by PPT1 (palmitoyl-protein thioesterase 1) mutations, and characterized by progressive psychomotor deterioration, brain atrophy, myoclonic jerk and visual impairment. INCL can be diagnosed by brain magnetic resonance image (MRI) prior to rapid deterioration stage. To date, there is no INCL patient whose manifestation was caused by uniparental isodisomy (UPiD). PATIENT: We reported a girl diagnosed with INCL. Genetic analysis revealed a novel PPT1 mutation c.20_47del28:p.Leu7Hisfs*21. Only the father of the patient was found as a carrier of this mutation. SNP array showed the mutation became homozygous by paternal UPiD of chromosome 1. DISCUSSION: Although ICNL is a rare disease except in Finland, it is not difficult to diagnose it since the clinical symptoms and MRI findings are characteristic. Genetic testing is useful for definitive diagnosis, and distinction of UPiD is essential for genetic counseling. PMID- 26846732 TI - Regular screening of esophageal cancer for 248 newly diagnosed hypopharyngeal squamous cell carcinoma by unsedated transnasal esophagogastroduodenoscopy. AB - OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is common in hypopharyngeal squamous cell carcinoma (HSCC) patients. This prospective study is to reveal the prevalence of simultaneous ESCC in newly diagnosed HSCC patients by unsedated transnasal esophagogastroduodenoscopy (EGD) and to analyze the clinical predictors for simultaneous esophageal lesions and their survival. MATERIALS AND METHODS: 248 patients with newly diagnosed HSCC and without previous head and neck cancer between 2007 and 2014 were prospectively evaluated for HSCC and simultaneous esophageal lesions by unsedated transnasal EGD. The clinical factors for simultaneous esophageal lesions were evaluated. Survival analysis of the HSCC patients receiving complete treatment was done. RESULTS: The mean age was 58years. 170 HSCC (68.5%) were classified as T3-T4. The procedures were successfully performed (98.4%), except 4 huge tumors. 174 HSCC (85.7%, out of 203 tumors biopsied) were pathologically proved malignancy by this technique. Regarding esophageal lesions (45.5%), ESCC occurred in 36 patients (14.8%), dysplasia without ESCC occurred in 23 (9.4%) and Lugol voiding lesion without ESCC or dysplasia occurred in 52 (21.3%). Alcohol drinking (adjusted OR: 6.95, p<0.05) and N3 classification (adjusted OR: 2.41, p<0.05) of HSCC were the independent risk factors for the presence of esophageal lesions. The overall survival of the HSCC patients with ESCC was significantly lower than those without ESCC (p=0.013). CONCLUSIONS: Unsedated transnasal EGD is a promising technique for diagnosis of HSCC and simultaneous ESCC. Simultaneous esophageal lesions including ESCC (15%) are common in newly diagnosed HSCC patients, especially with alcohol drinking or N3 disease. PMID- 26846733 TI - Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate. AB - BACKGROUND AND OBJECTIVE: Ablative fractional laser (AFXL) facilitates delivery of topical methotrexate (MTX). This study investigates impact of laser-channel depth on topical MTX-delivery. MATERIALS AND METHODS: MTX (1% [w/v]) diffused for 21 hours through AFXL-exposed porcine skin in in vitro Franz Cells (n = 120). A 2,940 nm AFXL generated microscopic ablation zones (MAZs) into epidermis (11 mJ/channel, MAZ-E), superficial-dermis (26 mJ/channel, MAZ-DS), and mid-dermis (256 mJ/channel, MAZ-DM). High performance liquid chromatography (HPLC) was used to quantify MTX deposition in full-thickness skin, biodistribution profiles at specific skin levels, and transdermal permeation. Fluorescence microscopy was used to visualize UVC-activated MTX-fluorescence (254 nm) and semi-quantify MTX distribution in skin. RESULTS: AFXL increased topical MTX-delivery (P < 0.001). Without laser exposure, MTX-concentration in full-thickness skin was 0.07 mg/cm(2) , increasing sixfold (MAZ-E), ninefold (MAZ-DS), and 11-fold (MAZ-DM) after AFXL (P < 0.001). Deeper MAZs increased MTX-concentrations in all skin layers (P < 0.038) and favored maximum accumulation in deeper skin layers (MAZ-E: 1.85 mg/cm(3) at 500 MUm skin-level vs. MAZ-DM: 3.75 mg/cm(3) at 800 MUm, P = 0.002). Ratio of skin deposition versus transdermal permeation remained constant, regardless of MAZ depth (P = 0.172). Fluorescence intensities confirmed MTX biodistribution through coagulation zones and into surrounding skin, regardless of thickness of coagulation zones (6-47 MUm, P >= 0.438). CONCLUSION: AFXL greatly increases topical MTX-delivery. Deeper MAZs deliver higher MTX concentrations than superficial MAZs, which indicates that laser channel depth may be important for topical delivery of hydrophilic molecules. Lasers Surg. Med. 48:519-529, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26846734 TI - Quercetin 2,4-Dioxygenase Activates Dioxygen in a Side-On O2-Ni Complex. AB - Quercetin 2,4-dioxygenase (quercetinase) from Streptomyces uses nickel as the active-site cofactor to catalyze oxidative cleavage of the flavonol quercetin. How this unusual active-site metal supports catalysis and O2 activation is under debate. We present crystal structures of Ni-quercetinase in three different states, thus providing direct insight into how quercetin and O2 are activated at the Ni(2+) ion. The Ni(2+) ion is coordinated by three histidine residues and a glutamate residue (E(76)) in all three states. Upon binding, quercetin replaces one water ligand at Ni and is stabilized by a short hydrogen bond through E(76) , the carboxylate group of which rotates by 90 degrees . This conformational change weakens the interaction between Ni and the remaining water ligand, thereby preparing a coordination site at Ni to bind O2. O2 binds side-on to the Ni(2+) ion and is perpendicular to the C2-C3 and C3-C4 bonds of quercetin, which are cleaved in the following reaction steps. PMID- 26846735 TI - Vascularized lymph node transfer and lymphovenous bypass: Novel treatment strategies for symptomatic lymphedema. AB - Lymphedema is a debilitating disease that is commonly caused by cancer and it is treatments in the developed world. Surgery is an option for refractory disease. Lymphovenous bypass and vascularized lymph node transfer are newer modalities that show great promise. Further work is necessary to determine proper patient selection and ensure minimum donor site morbidity. Liposuction and direct excision still have a role, especially in advanced cases. Further investigations into prevention of iatrogenic lymphedema are underway. J. Surg. Oncol. 2016;113:932-939. (c) 2016 Wiley Periodicals, Inc. PMID- 26846736 TI - Otologic Concerns for Cleft Lip and Palate Patient. AB - Understanding eustachian tube physiology and anticipating probable eustachian tube dysfunction is an important component of cleft palate management. This article provides a brief summary of the otologic physiology and issues that may be of concern to cleft palate management. It is of critical importance not only to provide primary closure of the cleft palate, but also to recognize that along with speech, hearing has a critical component to the educational and social success of all individuals. PMID- 26846737 TI - MicroRNA-301a promotes cell proliferation via PTEN targeting in Ewing's sarcoma cells. AB - MicroRNAs (miRNAs) regulate cell proliferation and differentiation by affecting gene expression at the post-transcriptional level by binding to complementary sequences within mRNAs in cancer cells, indicating that miRNAs can function as tumor suppressors or oncogenes. Recent studies showed that dysregulation of miRNA expression was associated with increased tumorigenicity and poor prognosis in several types of cancers, including Ewing's sarcoma (ES). To explore possible oncogenic factors in ES, we conducted microarray-based investigation and profiled the changes in miRNA expression and their effects on downstream mRNAs in five ES cell lines and human mesenchymal stem cells (hMSCs). miR-301a was significantly upregulated, while the phosphatase and tensin homolog (PTEN) expression was significantly downregulated in all tested ES cells as compared to hMSCs. When anti-miR-301a was transfected into ES cell lines, PTEN expression was significantly enhanced, suggesting that PTEN might be a target of miR-301a in ES cells. The expression of protein kinase B (Akt), which is inversely correlated with PTEN expression, was significantly downregulated in anti-miR-301a transfected cells. Additionally, the transfection of anti-miR-301a inhibited ES cell proliferation and cell cycle progression. Furthermore, downregulation of miR 301a in ES cells significantly suppressed tumor growth in vivo. Our results demonstrated the novel mechanism controlling PTEN expression via miR-301a in ES cells. Given that PTEN is a pivotal phosphatase factor that regulates cell cycle progression, apoptosis, and proliferation, these results might lead to development of new ES-related therapeutic targets. PMID- 26846738 TI - [In time: averting the legacy of kidney disease - focus on childhood]. PMID- 26846739 TI - Family relationships with pediatricians: the maternal views. AB - OBJECTIVE: To analyze the perception of pediatric guidelines by mothers at the time of consultation in private offices, in order to know how they assimilate, process and use the information received from the pediatricians. METHODS: Data collection was carried out by a questionnaire sent to participants by A total of 200 mothers from a virtual community in social networks participated in the research. The answers were transcribed using the Discourse of the Collective Subject method. The analyses were supported by the research qualitative perspective, from the viewpoint of the social representation theory. RESULTS: Three categories were obtained through data analysis: (1) assessing the pediatric guidelines (2) confronting theory and practice and (3) developing a critical view of the pediatric guidelines. These categories have elucidated that the level of knowledge of pediatric issues by mothers and their ability to use them when making decisions about the care of their babies, have a direct association between following or not the pediatric guidelines. CONCLUSIONS: The mother's decision on following the pediatrician's recommendations depends on two main factors: (a) certification of the updated and proven recommendations, according to the official health agencies; (b) support and recognition by the pediatrician of the maternal empowerment during the follow-up process. The mothers' practice of accessing knowledge through social networks hinders the pediatric monitoring. PMID- 26846740 TI - Determinants of the nutritional status of older adults in urban Lebanon. AB - AIM: To assess the nutritional status, and its association with sociodemographic factors, health and functional status of community-dwelling older adults living in the Greater Beirut area. METHODS: This was a cross-sectional study involving 905 randomly selected community dwelling older adults aged >=65 years living in Greater Beirut (Beirut and surrounding suburbs). Participants completed a standardized questionnaire on sociodemographic factors, health characteristics, and functional and nutritional status, based on the Mini Nutritional Assessment. RESULTS: Among the older adults who participated in the study, 2.8% (95% CI 0.01 0.03) were malnourished, and 45.5% (95% CI 0.42-0.48) were at risk of malnutrition. Sociodemographic variables were not associated with the nutritional status. Variables significantly associated with poorer nutritional status were: poor perception of general health (OR 1.58, 95%CI 1.28-1.97), more chronic diseases (OR 2.05, 95% CI1.26-3.33), poor perception of oral health (OR 1.36, 95% CI 1.14-1.61), depressive disorders (OR 1.76, 95% CI 1.30-2.40), higher body mass index (OR 1.98, 95% CI1.67-2.34) and disability (OR 5.80, 95% CI 1.96-17.11). CONCLUSIONS: The present study showed an unacceptable risk of malnutrition among Lebanese older adults, independent of age, sex and socioeconomic status. The presence of comorbidities, treated or not, affecting general and oral health emerged as major determinants of poor nutrition. Geriatr Gerontol Int 2017; 17: 424-432. PMID- 26846741 TI - Three extracellular dipeptidyl peptidases found in Aspergillus oryzae show varying substrate specificities. AB - Three extracellular dipeptidyl peptidase genes, dppB, dppE, and dppF, were unveiled by sequence analysis of the Aspergillus oryzae genome. We investigated their differential enzymatic profiles, in order to gain an understanding of the diversity of these genes. The three dipeptidyl peptidases were expressed using Aspergillus nidulans as the host. Each recombinant enzyme was purified and subsequently characterized. The enzymes displayed similar optimum pH values, but optimum temperatures, pH stabilities, and substrate specificities varied. DppB was identified as a Xaa-Prolyl dipeptidyl peptidase, while DppE scissile substrates were similar to the substrates for Aspergillus fumigatus DPPV (AfDPPV). DppF was found to be a novel enzyme that could digest both substrates for A. fumigatus DPPIV and AfDPPV. Semi-quantitative PCR revealed that the transcription of dppB in A. oryzae was induced by protein substrates and repressed by the addition of an inorganic nitrogen source, despite the presence of protein substrates. The transcription of dppE depended on its growth time, while the transcription of dppF was not affected by the type of the nitrogen source in the medium, and it started during the early stage of the fungal growth. Based on these results, we conclude that these enzymes may represent the nutrition acquisition enzymes. Additionally, DppF may be one of the sensor peptidases responsible for the detection of the protein substrates in A. oryzae environment. DppB may be involved in nitrogen assimilation control, since the transcription of dppB was repressed by NaNO3, despite the presence of protein substrates. PMID- 26846742 TI - A marine algicidal Thalassospira and its active substance against the harmful algal bloom species Karenia mikimotoi. AB - The aim of the present study was to obtain a marine bacterium active against Karenia mikimotoi from the East China Sea and to characterize its extracellular algicidal substances. Using preparative high-performance liquid chromatography (prep-HPLC) and electrospray ionization/quadrupole-time of flight mass spectrometer coupled with a high-performance liquid chromatography (LC/MS-Q-TOF) system, we purified the alga-lysing substance produced by strain ZR-2 and determined its molecular structure. Based on morphology and l6S ribosomal DNA (rDNA) sequence analysis, the ZR-2 strain was highly homologous to Thalassospira species. Algicidal activity against K. mikimotoi was detected in the cell-free filtrate but not in bacterial cells. The alga-lysing substance produced by ZR-2 was ethanol-soluble and thermostable, with a retention time of 6.3 min and a measured elemental composition of C7H5O2 ([M-H](-) ion at m/z 121.0295). The alga lysing substance produced by ZR-2 was determined to be benzoic acid. Compared with the negative control, both purified ZR-2 bacteria-free filtrate and standard benzoic acid promoted K. mikimotoi cell disruption and induced K. mikimotoi cell content leakage. Our study is the first to report benzoic acid activity against K. mikimotoi as well as production of benzoic acid by a Thalassospira species. PMID- 26846743 TI - Comparison of catalytic properties of multiple beta-glucosidases of Trichoderma reesei. AB - Ten putative Trichoderma reesei beta-glucosidase (BGL) isozymes were heterologously expressed in Escherichia coli and Aspergillus oryzae and purified to homogeneity. Catalytic properties of nine enzymes which showed hydrolytic activity on cellobiose and p-nitrophenyl-beta-D-glucopyranoside (pNPG) were investigated. Three BGLs, encoded by the genes cel3A, cel3B, and cel3E, contained a predicted signal peptide, showed higher hydrolytic activity on cello oligosaccharides than on pNPG, and preferred longer oligosaccharides. Another three putative extracellular BGLs, Cel3B, Cel3F, and Cel3G, and two intracellular enzymes, Cel3C and Cel3D, exhibited preference for pNPG. Intracellular Cel1A showed the highest affinity for cellobiose as a typical cellobiase. Four BGLs, Cel3A, Cel3B, Cel3E, Cel1A, that showed high activity against cello oligosaccharides were capable of catalyzing transglycosylation reactions from cellobiose, leading to formation of cellotriose and isomeric glucobioses. While Cel3A, Cel3B, and Cel3E synthesized mainly gentiobiose, glycosyl transfer reactions of Cel1A led mainly to sophorose and laminaribiose. Conversion of cellobiose to sophorose by Cel1A reached about 3.6 and 10 % at 1 and 10 % cellobiose concentration, respectively. The formation and persistence of individual cellobiose isomers in incubation mixtures of four BGLs (Cel3A, Cel3B, Cel3E, and Cel1A) with cellobiose correlated well with the k cat values for isomeric glucobioses. Cel1A also showed the lowest sensitivity to inhibition by glucose. Based on all studied catalytic properties, Cel1A appears to be unambiguously the best candidate for site-directed mutations or directed evolution toward improvement of activity, thermostability, and, eventually, efficiency of sophorose synthesis. PMID- 26846744 TI - Uranium bioprecipitation mediated by yeasts utilizing organic phosphorus substrates. AB - In this research, we have demonstrated the ability of several yeast species to mediate U(VI) biomineralization through uranium phosphate biomineral formation when utilizing an organic source of phosphorus (glycerol 2-phosphate disodium salt hydrate (C3H7Na2O6P.xH2O (G2P)) or phytic acid sodium salt hydrate (C6H18O24P6.xNa(+).yH2O (PyA))) in the presence of soluble UO2(NO3)2. The formation of meta-ankoleite (K2(UO2)2(PO4)2.6(H2O)), chernikovite ((H3O)2(UO2)2(PO4)2.6(H2O)), bassetite (Fe(++)(UO2)2(PO4)2.8(H2O)), and uramphite ((NH4)(UO2)(PO4).3(H2O)) on cell surfaces was confirmed by X-ray diffraction in yeasts grown in a defined liquid medium amended with uranium and an organic phosphorus source, as well as in yeasts pre-grown in organic phosphorus containing media and then subsequently exposed to UO2(NO3)2. The resulting minerals depended on the yeast species as well as physico-chemical conditions. The results obtained in this study demonstrate that phosphatase-mediated uranium biomineralization can occur in yeasts supplied with an organic phosphate substrate as sole source of phosphorus. Further understanding of yeast interactions with uranium may be relevant to development of potential treatment methods for uranium waste and utilization of organic phosphate sources and for prediction of microbial impacts on the fate of uranium in the environment. PMID- 26846745 TI - Characterization and evolution of an activator-independent methanol dehydrogenase from Cupriavidus necator N-1. AB - Methanol utilization by methylotrophic or non-methylotrophic organisms is the first step toward methanol bioconversion to higher carbon-chain chemicals. Methanol oxidation using NAD-dependent methanol dehydrogenase (Mdh) is of particular interest because it uses NAD(+) as the electron carrier. To our knowledge, only a limited number of NAD-dependent Mdhs have been reported. The most studied is the Bacillus methanolicus Mdh, which exhibits low enzyme specificity to methanol and is dependent on an endogenous activator protein (ACT). In this work, we characterized and engineered a group III NAD-dependent alcohol dehydrogenase (Mdh2) from Cupriavidus necator N-1 (previously designated as Ralstonia eutropha). This enzyme is the first NAD-dependent Mdh characterized from a Gram-negative, mesophilic, non-methylotrophic organism with a significant activity towards methanol. Interestingly, unlike previously reported Mdhs, Mdh2 does not require activation by known activators such as B. methanolicus ACT and Escherichia coli Nudix hydrolase NudF, or putative native C. necator activators in the Nudix family under mesophilic conditions. This enzyme exhibited higher or comparable activity and affinity toward methanol relative to the B. methanolicus Mdh with or without ACT in a wide range of temperatures. Furthermore, using directed molecular evolution, we engineered a variant (CT4-1) of Mdh2 that showed a 6-fold higher K cat/K m for methanol and 10-fold lower K cat/K m for n-butanol. Thus, CT4-1 represents an NAD-dependent Mdh with much improved catalytic efficiency and specificity toward methanol compared with the existing NAD dependent Mdhs with or without ACT activation. PMID- 26846747 TI - Erratum to: New Minimum Relative Humidity Requirements Are Expected to Lead to More Medical Device Failures. PMID- 26846746 TI - Therapeutic efficacy of oral immunization with a non-genetically modified Lactococcus lactis-based vaccine CUE-GEM induces local immunity against Helicobacter pylori infection. AB - The gastric bacterial pathogen Helicobacter pylori persistently colonizes the gastric mucosa of humans and plays a critical role in the development of gastritis, peptic ulceration and gastric adenocarcinoma. Consequently, the eradication of H. pylori might contribute to the prevention of H. pylori associated gastric diseases. In this study, a multi-epitope vaccine CTB-UE (CUE) was displayed on the surface of non-genetically modified Lactococcus lactis particles (GEM) to enhance immunogenicity. This particulate vaccine CUE-GEM induced serum and mucosal specific antibody responses against native H. pylori urease and provided potent protection to eliminate H. pylori colonization and relieve gastritis in an H. pylori-infected BALB/c mouse model. The immuno protective mechanisms are highly associated with CD4(+) Th cell-mediated and humoral immunity, especially local immunity. There might be two main aspects of this association. One aspect is related to the suppression of urease activity by promotion of the production of specific mucosal neutralizing antibody. The other aspect is correlated with alleviating gastritis by regulating the gastric pro inflammatory cytokine profile, especially IFN-gamma and IL-17. These results demonstrated that conjugating antigen vaccines with GEM particles could lead to promising oral therapeutic vaccine formulations against H. pylori infection. PMID- 26846748 TI - Wearable Computing for Health Care. PMID- 26846750 TI - Cloud Image Data Center for Healthcare Network in Taiwan. AB - This paper investigates how a healthcare network in Taiwan uses a practical cloud image data center (CIDC) to communicate with its constituent hospital branches. A case study approach was used. The study was carried out in the central region of Taiwan, with four hospitals belonging to the Veterans Hospital healthcare network. The CIDC provides synchronous and asynchronous consultation among these branches. It provides storage, platforms, and services on demand to the hospitals. Any branch-client can pull up the patient's medical images from any hospital off this cloud. Patients can be examined at the branches, and the images and reports can be further evaluated by physicians in the main Taichung Veterans General Hospital (TVGH) to enhance the usage and efficiency of equipment in the various branches, thereby shortening the waiting time of patients. The performance of the CIDC over 5 years shows: (1) the total number of cross hospital images accessed with CDC in the branches was 132,712; and (2) TVGH assisted the branches in keying in image reports using the CIDC 4,424 times; and (3) Implementation of the system has improved management, efficiency, speed and quality of care. Therefore, the results lead to the recommendation of continuing and expanding the cloud computing architecture to improve information sharing among branches in the healthcare network. PMID- 26846751 TI - Hemopericardium after laparoscopic perihiatal procedures: high index of suspicion facilitates early diagnosis and successful nonoperative management. PMID- 26846749 TI - Online Patient Education for Chronic Disease Management: Consumer Perspectives. AB - Patient education plays an important role in chronic disease management. The aim of this study is to identify patients' preferences in regard to the design features of effective online patient education (OPE) and the benefits. A review of the existing literature was conducted in order to identify the benefits of OPE and its essential design features. These design features were empirically tested by conducting survey with patients and caregivers. Reliability analysis, construct validity and regression analysis were performed for data analysis. The results identified patient-tailored information, interactivity, content credibility, clear presentation of content, use of multimedia and interpretability as the essential design features of online patient education websites for chronic disease management. PMID- 26846752 TI - Anti-angiogenic therapy for normalization of tumor vasculature: A potential effect of Buyang Huanwu decoction on nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential. AB - The present study aimed to investigate the effect of Buyang Huanwu decoction (BYHWD) on tumor growth, metastasis and angiogenesis in nude mice bearing human hepatocellular carcinoma (HCC) HCCLM3 xenografts. A total of 96 nude mice bearing HCCLM3 xenografts were randomly divided into four groups: BYHWD group (LB), Yi-qi decoction group (LY), Huo-xue decoction group (LH) and model group (LM). Each of these groups was divided into three subgroups (n=8), which were observed on days 21, 25, 38 following treatment, respectively. The tumor weights, volumes and pulmonary metastases were recorded. The expression of CD105 and the microvessel density (MVD) were assessed, and the expression levels of vascular endothelial growth factor (VEGF), hypoxia-inducible factor 1alpha (HIF-1alpha), and regulator of G protein signaling 5 (RGS-5) were analyzed using immunohistochemical staining. Compared with the LM group, no significant decrease in tumor weight or volume were observed in the herbal medicine treatment groups, the number of the metastases in the lungs decreased, whereas the expression levels of RGS-5 and HIF 1alpha decreased in the LB group on day 35. However, the expression levels of VEGF increased in the LB group on days 28 and 35 post-treatment. The results of the present study suggested that BYHWD may inhibit angiogenesis and metastasis by affecting the expression levels of VEGF, RGS-5 and HIF-1alpha, and suggested that BYHWD may contribute to the tumor microenvironment and vasculature normalization in HCC. PMID- 26846753 TI - Change blindness for cast shadows in natural scenes: Even informative shadow changes are missed. AB - Previous work has shown that human observers discount or neglect cast shadows in natural and artificial scenes across a range of visual tasks. This is a reasonable strategy for a visual system designed to recognize objects under a range of lighting conditions, since cast shadows are not intrinsic properties of the scene-they look different (or disappear entirely) under different lighting conditions. However, cast shadows can convey useful information about the three dimensional shapes of objects and their spatial relations. In this study, we investigated how well people detect changes to cast shadows, presented in natural scenes in a change blindness paradigm, and whether shadow changes that imply the movement or disappearance of an object are more easily noticed than shadow changes that imply a change in lighting. In Experiment 1, a critical object's shadow was removed, rotated to another direction, or shifted down to suggest that the object was floating. All of these shadow changes were noticed less often than changes to physical objects or surfaces in the scene, and there was no difference in the detection rates for the three types of changes. In Experiment 2, the shadows of visible or occluded objects were removed from the scenes. Although removing the cast shadow of an occluded object could be seen as an object deletion, both types of shadow changes were noticed less often than deletions of the visible, physical objects in the scene. These results show that even informative shadow changes are missed, suggesting that cast shadows are discounted fairly early in the processing of natural scenes. PMID- 26846754 TI - Moyamoya Disease, Still a Mysterious Disorder. PMID- 26846755 TI - Moyamoya Disease: Epidemiology, Clinical Features, and Diagnosis. AB - Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease characterized by progressive stenosis at the terminal portion of the internal carotid artery and an abnormal vascular network at the base of the brain. Although its etiology remains unknown, recent genetic studies identified RNF213 in the 17q25-ter region as an important susceptibility gene of MMD among East Asian populations. Possibly because of genetic differences, MMD is relatively common in people living in East Asian countries such as Korea and Japan, compared to those in the Western Hemisphere. The prevalence of MMD appears to be slightly lower among Chinese, compared to Koreans or Japanese. There are two peaks of incidence with different clinical presentations, at around 10 years and 30-40 years. The peak appears to occur later in women than men. In children, ischemic symptoms, especially transient ischemic attacks, are predominant. Intellectual decline, seizures, and involuntary movements are also more common in this age group. In contrast, adult patients present with intracranial hemorrhage more often than pediatric patients. In patients with MMD, intracerebral hemorrhage is more often accompanied by intraventricular hemorrhage than in patients with hypertensive intracerebral hemorrhage. These different age peaks and different clinical presentations in each age group are also observed in MMD patients in the USA. Catheter angiography is the diagnostic method of choice. Magnetic resonance (MR) angiography and computed tomographic angiography are noninvasive diagnostic methods. High-resolution vessel wall MR imaging also helps diagnose MMD by revealing concentric vessel wall narrowing with basal collaterals. PMID- 26846756 TI - The Pathophysiology of Moyamoya Disease: An Update. AB - Moyamoya disease (MMD) is a unique cerebrovascular disease characterized by the progressive stenosis of large intracranial arteries and a hazy network of basal collaterals called moyamoya vessels. Because the etiology of MMD is unknown, its diagnosis is based on characteristic angiographic findings. Re-vascularization techniques (e.g., bypass surgery) are used to restore perfusion, and are the primary treatment for MMD. There is no specific treatment to prevent MMD progression. This review summarizes the recent advances in MMD pathophysiology, including the genetic and circulating factors related to disease development. Genetic and environmental factors may play important roles in the development of the vascular stenosis and aberrant angiogenesis in complex ways. These factors include the related changes in circulating endothelial/smooth muscle progenitor cells, cytokines related to vascular remodeling and angiogenesis, and endothelium, such as caveolin which is a plasma membrane protein. With a better understanding of MMD pathophysiology, nonsurgical approaches targeting MMD pathogenesis may be available to stop or slow the progression of this disease. The possible strategies include targeting growth factors, retinoic acid, caveolin 1, and stem cells. PMID- 26846757 TI - Moyamoya Disease: Treatment and Outcomes. AB - Although the pathogenesis of moyamoya disease (MMD) has not been fully elucidated, the effectiveness of surgical revascularization in preventing stroke has been addressed by many studies. The main mechanism of surgical revascularization is augmenting the intracranial blood flow using an external carotid system by either direct bypass or pial synangiosis. This can improve resting cerebral blood flow as well as vascular reserve capacity. For direct revascularization, the superficial temporal artery is used as the donor artery in most cases, although the occipital artery may be used in limited cases. Usually, the cortical branch of the middle cerebral artery is selected as the recipient of direct anastomosis. As for indirect revascularization, various techniques using different kinds of connective tissues have been introduced. In some cases, reinforcing the anterior cerebral artery and the posterior cerebral artery territories can be considered. The effectiveness of surgical revascularization for preventing ischemic stroke had been generally accepted by many studies. However, for preventing hemorrhagic stroke, new evidence has been added by a recent randomized controlled trial. The incidence of peri-operative complications such as stroke and hyperperfusion syndrome seems to be high due to the nature of the disease and technical demands for treatment. Preventing and adequately managing these complications are essential for ensuring the benefits of surgery. PMID- 26846758 TI - Prediction of Upper Limb Motor Recovery after Subacute Ischemic Stroke Using Diffusion Tensor Imaging: A Systematic Review and Meta-Analysis. AB - Early evaluation of the pyramidal tract using Diffusion Tensor Imaging (DTI) is a prerequisite to decide the optimal treatment or to assess appropriate rehabilitation. The early predictive value of DTI for assessing motor and functional recovery in ischemic stroke (IS) has yielded contradictory results. The purpose is to systematically review and summarize the current available literature on the value of Fractional Anisotropy (FA) parameter of the DTI in predicting upper limb motor recovery after sub-acute IS. MEDLINE, PubMed, EMBASE, Google Scholar and Cochrane CENTRAL searches were conducted from January 1, 1950, to July 31, 2015, which was supplemented with relevant articles identified in the references. Correlation between FA and upper limb motor recovery measure was done. Heterogeneity was examined using Higgins I-squared, Tau-squared. Summary of correlation coefficient was determined using Random Effects model. Out of 166 citations, only eleven studies met the criteria for inclusion in the systematic review and six studies were included in the meta-analysis. A random effects model revealed that DTI parameter FA is a significant predictor for upper limb motor recovery after sub-acute IS [Correlation Coefficient=0.82; 95% Confidence Interval-0.66 to 0.90, P value<0.001]. Moderate heterogeneity was observed (Tau squared=0.12, I-squared=62.14). The studies reported so far on correlation between DTI and upper limb motor recovery are few with small sample sizes. This meta-analysis suggests strong correlation between DTI parameter FA and upper limb motor recovery. Well-designed prospective trials embedded with larger sample size are required to establish these findings. PMID- 26846759 TI - Susceptibility-Weighted Imaging for Detection of Thrombus in Acute Cardioembolic Stroke. AB - BACKGROUND AND PURPOSE: Susceptibility-weighted imaging (SWI) can show an intravascular thrombus as a hypointense susceptibility vessel sign (SVS). In this study, we investigated the usefulness of SWI in the detection of an intravascular thrombus in acute cardioembolic stroke by comparing the SVS on SWI to the vessel status on time-of-flight magnetic resonance angiography (MRA). METHODS: We consecutively enrolled patients with cardioembolic stroke in the anterior circulation within 3 days from stroke onset. The frequency and location of the SVS on SWI were compared with those of occlusion on MRA. RESULTS: One hundred and twenty-two patients were conclusively enrolled in this study. The SVS was observed in 75.4% (92/122) of the enrolled patients. MRA showed occlusion in 57% (70/122) of the enrolled patients. The SVS was identified in all 70 patients with occlusion on MRA. The SVS was observed in 22 (42.3%) of 52 patients without occlusion on MRA (P<0.001), which was identified mainly in post-bifurcation segments of the middle cerebral artery: the M2 segment in 4 patients, M3 segment in 10 patients, M4 segment in 4 patients, A3 segment in 1 patient, and multiple segments in 2 patients. The mean length of the SVS in the M1 segment was 13.65 mm (median: 12.39 mm, length range: 2.70-39.50 mm). CONCLUSIONS: SWI can provide useful information about the thrombus location, the presence of a single thrombus or multiple thrombi especially in distal intracranial arteries, and the thrombus burden, all in acute cardioembolic stroke. PMID- 26846760 TI - Effect and Safety of Rosuvastatin in Acute Ischemic Stroke. AB - BACKGROUND AND PURPOSE: The benefit of statins in acute stroke remains uncertain. Statins may prevent stroke recurrence during the acute stage of stroke via pleiotropic effects. However, statins may increase the risk of intracerebral hemorrhage. We investigated the effect and safety of rosuvastatin in acute stroke patients. METHODS: This randomized, double-blind, multi-center trial compared rosuvastatin 20 mg and placebo in statin-naive stroke patients who underwent diffusion-weighted imaging (DWI) within 48 hours after symptom onset. The primary outcome was occurrence of new ischemic lesions on DWI at 5 or 14 days. RESULTS: This trial was stopped early after randomization of 316 patients due to slow enrollment. Among 289 patients with at least one follow-up imaging, the frequency of new ischemic lesions on DWI was not different between groups (rosuvastatin: 27/137, 19.7% vs. placebo: 36/152, 23.6%) (relative risk 0.83, 95% confidence interval 0.53-1.30). Infarct volume growth at 5 days (log-transformed volume change, rosuvastatin: 0.2+/-1.0 mm(3) vs. placebo: 0.3+/-1.3 mm(3); P=0.784) was not different, either. However, hemorrhagic infarction or parenchymal/subarachnoid hemorrhage on gradient-recalled echo magnetic resonance imaging occurred less frequently in the rosuvastatin group (6/137, 4.4%) than the placebo group (22/152, 14.5%, P=0.007). Among 314 patients with at least one dose of study medication, progression or clinical recurrence of stroke tended to occur less frequently in the rosuvastatin group (1/155, 0.6% vs. 7/159, 4.4%, P=0.067). Adverse events did not differ between groups. CONCLUSIONS: The efficacy of rosuvastatin in reducing recurrence in acute stroke was inconclusive. However, statin use was safe and reduced hemorrhagic transformation. PMID- 26846762 TI - Petroclival Meningioma Accompanying Posterior Cerebral Artery Infarction. PMID- 26846761 TI - Update of the Korean Clinical Practice Guidelines for Endovascular Recanalization Therapy in Patients with Acute Ischemic Stroke. AB - Patients with severe stroke due to acute large cerebral artery occlusion are likely to be severely disabled or dead without timely reperfusion. Previously, intravenous tissue plasminogen activator (IV-TPA) within 4.5 hours after stroke onset was the only proven therapy, but IV-TPA alone does not sufficiently improve the outcome of patients with acute large artery occlusion. With the introduction of the advanced endovascular therapy, which enables more fast and more successful recanalization, recent randomized trials consecutively and consistently demonstrated the benefit of endovascular recanalization therapy (ERT) when added to IV-TPA. Accordingly, to update the recommendations, we assembled members of the writing committee appointed by the Korean Stroke Society, the Korean Society of Interventional Neuroradiology, and the Society of Korean Endovascular Neurosurgeons. Reviewing the evidences that have been accumulated, the writing members revised recommendations, for which formal consensus was achieved by convening a panel composed of 34 experts from the participating academic societies. The current guideline provides the evidence-based recommendations for ERT in patients with acute large cerebral artery occlusion regarding patient selection, treatment modalities, neuroimaging evaluation, and system organization. PMID- 26846763 TI - Population genetic analysis of the GlobalFiler STR loci in 748 individuals from the Kazakh population of Xinjiang in northwest China. AB - The six-dye GlobalFilerTM Express PCR amplification kit incorporates 21 commonly used autosomal short tandem repeat (STR) loci and three gender determination loci. In this study, we analyzed the GlobalFiler STR loci on 748 unrelated individuals from a Chinese Kazakh population of Xinjiang, China. No significant deviations from Hardy-Weinberg equilibrium and linkage disequilibrium were observed within and between 21 autosomal STR loci. SE33 showed the greatest power of discrimination in Kazakh population. The combined power of discrimination of Kazakh was 99.999999999999999999999996797 %. No significant differences of allele frequencies were observed between Kazakh and Uyghur at all 15 tested STR loci, as well as Mongolian. Significant differences were only observed between Kazakh and the other Chinese populations at TH01. Multiple STR loci showed significant differences between Kazakh and Arab, as well as South Portuguese. The multidimensional scaling plot (MDS) plot and neighbor-joining tree also showed Kazakh is genetically close to Uyghur. PMID- 26846764 TI - A genetic portrait of Oraon Indian tribe drawn with 15 autosomal and 17 Y chromosomal STR markers. AB - An analysis of 15 autosomal short tandem repeat (STR) loci and 17 Y-STR loci was performed in 123 unrelated members of the Oraon tribal community of Central India. The combined power of discrimination (CPD) and combined power of exclusion (CPE) were greater than 0.99999 and 0.999989, respectively, for autosomal STRs. In addition, a total of 58 distinct Y-STR haplotypes were observed out of which 54 Y-STR haplotypes were observed only once. The haplotype diversity and discrimination capacity for 17 Y-STR loci was 0.997 and 0.906, respectively. PMID- 26846765 TI - Comparison of porcine thorax to gelatine blocks for wound ballistics studies. AB - Tissue simulants are typically used in ballistic testing as substitutes for biological tissues. Many simulants have been used, with gelatine amongst the most common. While two concentrations of gelatine (10 and 20 %) have been used extensively, no agreed standard exists for the preparation of either. Comparison of ballistic damage produced in both concentrations is lacking. The damage produced in gelatine is also questioned, with regards to what it would mean for specific areas of living tissue. The aim of the work discussed in this paper was to consider how damage caused by selected pistol and rifle ammunition varied in different simulants. Damage to gelatine blocks 10 and 20 % in concentration were tested with 9 mm Luger (9 * 19 full metal jacket; FMJ) rounds, while damage produced by .223 Remington (5.56 * 45 Federal Premium(r) Tactical(r) Bonded(r)) rounds to porcine thorax sections (skin, underlying tissue, ribs, lungs, ribs, underlying tissue, skin; backed by a block of 10 % gelatine) were compared to 10 and 20 % gelatine blocks. Results from the .223 Remington rifle round, which is one that typically expands on impact, revealed depths of penetration in the thorax arrangement were significantly different to 20 % gelatine, but not 10 % gelatine. The level of damage produced in the simulated thoraxes was smaller in scale to that witnessed in both gelatine concentrations, though greater debris was produced in the thoraxes. PMID- 26846767 TI - Pleural fluid accumulation detectable on paediatric post-mortem imaging: a possible marker of interval since death? AB - OBJECTIVES: The aim of this preliminary study is to evaluate whether pleural fluid accumulates following death in a predictable manner, in particular whether such collections are related to post-mortem interval. METHODS: Images acquired by post-mortem magnetic resonance imaging (PMMR) were both subjectively and objectively assessed for extent of pleural fluid accumulation. Total thoracic volume and pleural fluid volume were calculated using segmentation functions on OSIRIX software. The percentage of pleural fluid as a percentage of thoracic volume was calculated, to account for variation in subject size. The cause of death as per the final autopsy report and the interval from death to imaging were also recorded. RESULTS: Twelve perinatal deaths/stillbirths (mean gestation 38 weeks, range 24-48 weeks, male/female 5:7) and 11 childhood deaths (mean age 1 year, range 1 day-4 years, male/female 3:8) were assessed. The mean interval from death to imaging for all cases was 7.5 days (range 1-23 days). Pleural fluid was present in almost all cases, and the mean percentage pleural effusion as a proportion of thoracic volume was 3.3 % (range 0.2-9.5 %). There was a significant correlation between the post-mortem interval and the amount of pleural fluid in childhood deaths (p < 0.05) but no significant relationship for perinatal deaths. CONCLUSION: The accumulation of pleural fluid detectable on PMMR in children is related to post-mortem interval. If this holds for a larger population, it may therefore be a useful marker for estimating time of death. A similar relationship was not found for perinatal deaths and stillbirths, the reasons for which remain uncertain. PMID- 26846766 TI - Post-mortem whole-exome sequencing (WES) with a focus on cardiac disease associated genes in five young sudden unexplained death (SUD) cases. AB - Sudden death of healthy young adults in the absence of any medical reason is generally categorised as autopsy-negative sudden unexplained death (SUD). Approximately 30 % of all SUD cases can be explained by lethal sequence variants in cardiac genes causing disturbed ion channel functions (channelopathies) or minimal structural heart abnormalities (cardiomyopathies). The aim of this study was to perform whole-exome sequencing (WES) in five young SUD cases in order to identify potentially disease-causing mutations with a focus on 184 genes associated with cardiac diseases or sudden death. WES analysis enabled the identification of damaging-predicted cardiac sequence alterations in three out of five SUD cases. Two SUD victims carried disease-causing variants in long QT syndrome (LQTS)-associated genes (KCNH2, SCN5A). In a third case, WES identified variants in two genes involved in mitral valve prolapse and thoracic aortic aneurism (DCHS1, TGFbeta2). The genome of a fourth case carried several minor variants involved in arrhythmia pointing to a multigene influence that might have contributed to sudden death. Our results confirm that post-mortem genetic testing in SUD cases in addition to the conventional autopsy can help to identify familial cardiac diseases and can contribute to the identification of genetic risk factors for sudden death. PMID- 26846770 TI - Analysis of a stochastic tri-trophic food-chain model with harvesting. AB - We consider a tri-trophic stochastic food-chain model with harvesting. We first establish critical values between persistence in mean and extinction for each species. The results show that persistence and extinction of a species only depends on the demographic impacts of environmental stochasticity on the species and species at lower tropic levels; however, the mean abundance of a species depends on the impacts of environmental stochasticity at all trophic levels. Then we consider stability in distribution of the model. Finally, we provide a necessary and sufficient condition for existence of optimal harvesting strategy and give the optimal harvesting effort and maximum of sustainable yield. The results show that the optimal harvesting strategy is closely related to the stochastic noises in the model. PMID- 26846768 TI - Comparison of endogenous GHB concentrations in blood and hair in death cases with emphasis on the post mortem interval. AB - Gamma-hydroxybutyric acid (GHB) is an endogenous compound which has a story of clinical use and illicit abuse since the 1960's. The possibility to use a multi sample approach for GHB evaluation, including whole blood and hair, to better characterize a forensic toxicology case and evaluate a possible causal association with the death is an exciting up-to-date issue. In addition, its post mortem behaviour, namely regarding degradation and metabolism, has been increasingly investigated as a putative biomarker for post-mortem interval (PMI) estimation. Thus, in order to contribute to clarification of this specific aspect, whole blood and hair post-mortem GHB levels were evaluated in 32 real cases with previous information on death and autopsy data. The results obtained suggest that the PMI (until 5 days between death and sampling) influences GHB whole blood concentration, but not GHB levels in hair samples. No differences were encountered for the other parameters evaluated, including age, gender, cause of death and presence or absence of substances. This study brings new insights regarding the usefulness of GHB levels in forensic toxicology, which might be further strengthened with larger, but comparable, studies from other laboratories and institutions in the context of legal medicine. PMID- 26846769 TI - Modeling Future Cardiovascular Disease Mortality in the United States: National Trends and Racial and Ethnic Disparities. AB - BACKGROUND: Accurate forecasting of cardiovascular disease mortality is crucial to guide policy and programming efforts. Prior forecasts often have not incorporated past trends in rates of reduction in cardiovascular disease mortality. This creates uncertainties about future trends in cardiovascular disease mortality and disparities. METHODS AND RESULTS: To forecast US cardiovascular disease mortality and disparities to 2030, we developed a hierarchical bayesian model to determine and incorporate prior age, period, and cohort effects from 1979 to 2012, stratified by age, sex, and race, which we combined with expected demographic shifts to 2030. Data sources included the National Vital Statistics System, Surveillance, Epidemiology, and End Results (SEER) single-year population estimates, and US Bureau of Statistics 2012 national population projections. We projected coronary disease and stroke deaths to 2030, first on the basis of constant age, period, and cohort effects at 2012 values, as is most commonly done (conventional), and then with the use of more rigorous projections incorporating expected trends in age, period, and cohort effects (trend based). We primarily evaluated absolute mortality. The conventional model projected total coronary and stroke deaths by 2030 to increase by ~18% (67 000 additional coronary deaths per year) and 50% (64 000 additional stroke deaths per year). Conversely, the trend-based model projected that coronary mortality would decrease by 2030 by ~27% (79 000 fewer deaths per year) and stroke mortality would remain unchanged (200 fewer deaths per year). Health disparities will be improved in stroke deaths but not coronary deaths. CONCLUSIONS: After prior mortality trends and expected demographic shifts are accounted for, total US coronary deaths are expected to decline, whereas stroke mortality will remain relatively constant. Health disparities in stroke but not coronary deaths will be improved but not eliminated. These age, period, and cohort approaches offer more plausible predictions than conventional estimates. PMID- 26846771 TI - An Uncommon Lesion of the Otic Capsule. Fibrous dysplasia. PMID- 26846773 TI - Beclomethasone Dipropionate Nasal Aerosol in Patients with Perennial Allergic Rhinitis (BALANCE) study: 6-month results. AB - BACKGROUND: Perennial allergic rhinitis (PAR) exerts significant quality-of-life and economic burdens on society. Beclomethasone dipropionate (BDP) nasal aerosol is the first nonaqueous, hydrofluoroalkane-propelled intranasal corticosteroid approved for patients in the United States to treat PAR and seasonal allergic rhinitis. OBJECTIVE: To evaluate real-world effectiveness of BDP nasal aerosol from the patient's perspective by using a postmarketing observational registry. METHODS: Patients (N = 824) from 43 U.S. study sites completed monthly patient reported outcome instruments, including the Rhinitis Control Assessment Test (primary outcome variable), Treatment Satisfaction Questionnaire for Medication, Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy-Specific, Pittsburgh Sleep Quality Index, and Mini Rhinoconjunctivitis Quality of Life Questionnaire for 6 months. RESULTS: The primary outcome assessment (Rhinitis Control Assessment Test score) (N = 527) indicated significant symptomatic improvement over baseline beginning at month 1 (p < 0.001), with >78.8% of respondents who achieved clinically meaningful improvement over 6 months. Secondary outcome measures Mini Rhinoconjunctivitis Quality of Life Questionnaire (p < 0.001), Pittsburgh Sleep Quality Index (p < 0.001), and Treatment Satisfaction Questionnaire for Medication-9 scales of effectiveness (p < 0.001), global satisfaction (p = 0.001), and patient-rated convenience (p = 0.03), significantly increased from baseline to month 6. Five of seven measurements of the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy-Specific, with the exception of work time missed and class time missed, were significantly (p < 0.001) improved in patients treated with BDP compared with baseline. CONCLUSIONS: Treatment with nonaqueous BDP nasal aerosol in a real-world setting significantly improved PAR symptoms and measures of quality of life, work, and school-related activities, and is associated with high patient satisfaction, reduced productivity loss and activity impairment, and improvement in sleep quality. PMID- 26846772 TI - Conversion of photosystem II dimer to monomers during photoinhibition is tightly coupled with decrease in oxygen-evolving activity in the diatom Chaetoceros gracilis. AB - The rapid turnover of photosystem II (PSII) in diatoms is thought to be at an exceptionally high rate compared with other oxyphototrophs; however, its molecular mechanisms are largely unknown. In this study, we examined the photodamage and repair processes of PSII in the marine centric diatom Chaetoceros gracilis incubated at 30 or 300 MUmol photons m-2 s-1 in the presence of a de novo protein-synthesis inhibitor. When de novo protein synthesis was blocked by chloramphenicol (Cm), oxygen-evolving activity gradually decreased even at 30 MUmol photons m-2 s-1 and could not be detected at 12 h. PSII inactivation was enhanced by higher illumination. Using Cm-treated cells, the conversion of PSII dimer to monomers was observed by blue native PAGE. The rate of PSII monomerization was very similar to that of the decrease in oxygen-evolving activity under both light conditions. Immunological detection of D1 protein in the Cm-treated cells showed that the rate of D1 degradation was slower than that of the former two events, although it was more rapid than that observed in other oxyphototrophs. Thus, the three accelerated events, especially PSII monomerization, appear to cause the unusually high rate of PSII turnover in diatoms. PMID- 26846774 TI - Proton pump inhibitors and fracture: do they do what it says on the tin? PMID- 26846775 TI - The epidemiology of fractures in Denmark in 2011. AB - In the present study, we used national health care databases to estimate fracture incidence rates (IRs) and compared these IRs based on imputed data. We showed that imputation could lead to both over- and underestimation of IRs, and future research should therefore focus on how to improve those imputations. INTRODUCTION: Osteoporosis is a major public health burden through associated (osteoporotic) fractures. In Denmark, the incidence rates (IRs) of hip fracture are widely available. However, there is limited data about other fracture sites. A recent report could only provide imputed IRs, although nationwide data is readily available in electronic healthcare databases. Therefore, our aim was to estimate fracture site-specific IRs for Denmark in 2011 and to compare those to the previously reported imputed data. METHODS: Data from the Danish National Hospital Discharge Register was used to estimate age- and gender-specific IRs for any fracture as well as for different fracture sites in the Danish population aged 20 years and older in 2011. Hip fracture IRs were stratified to sub-sites, and IRs were determined for all hip fractures which were confirmed by surgery. RESULTS: The total number of incident fractures in 2011 was 80,760 (IR 191, 95 % confidence interval (CI) 190-192 (per 10,000 person-years)), of which 35,398 (43.8 %, IR 171, 95 % CI 169-173) occurred in men and 45,362 (56.2 %, IR 211, 95 % CI 209-213) in women. The majority of the fractures occurred in the population aged 50 years and older (n = 50,470, IR 249, 95 % CI 247-251). The numbers of any hip fracture were lower than the previously imputed estimates, whereas the number of forearm fractures was higher. CONCLUSION: We showed age- and gender-specific fracture rates for any fracture as well as for different fracture sites. The IRs of most fracture sites increased with age. Estimating the number of fractures for Denmark based on imputation of data from other countries led to both over- and underestimation. Future research should therefore focus on how to improve those imputations as not all countries have nationwide registry data. PMID- 26846776 TI - The predicted lifetime costs and health consequences of calcium and vitamin D supplementation for fracture prevention-the impact of cardiovascular effects. AB - Some studies indicate that calcium supplementation increases cardiovascular risk. We assessed whether such effects could counterbalance the fracture benefits from supplementation. Accounting for cardiovascular outcomes, calcium may cause net harm and would not be cost-effective. Clinicians may do well considering cardiovascular effects when prescribing calcium supplementation. INTRODUCTION: Accounting for possible cardiovascular effect of calcium and vitamin D supplementation (CaD), the aims of this study were to assess whether CaD on balance would improve population health and to evaluate the cost-effectiveness of such supplementation. METHODS: We created a probabilistic Markov simulation model that was analysed at the individual patient level. We analysed 65-year-old Norwegian women with a 2.3 % 10-year risk of hip fracture and a 9.3 % risk of any major fracture according to the WHO fracture risk assessment tool (FRAX(r)). Consistent with a recent Cochrane review, we assumed that CaD reduces the risk of hip, vertebral, and wrist fractures by 16, 11, and 5 %, respectively. We included the increased risk of acute myocardial infarction (AMI) and stroke under a no-, medium-, and high-risk scenario. RESULTS: Assuming no cardiovascular effects, CaD supplementation produces improved health outcomes resulting in an incremental gain of 0.0223 quality-adjusted life years (QALYs) and increases costs by ?322 compared with no treatment (cost-effectiveness ratio ?14,453 per QALY gained). Assuming a Norwegian cost-effectiveness threshold of ?60,000 per QALY, CaD is likely to be considered a cost-effective treatment alternative. In a scenario with a medium or high increased risk of cardiovascular events, CaD produces net health losses, respectively, -0.0572 and -0.0784 QALY at additional costs of ?481 and ?1033. CONCLUSIONS: We conclude that the magnitude of potential cardiovascular side effects is crucial for the effectiveness and cost effectiveness of CaD supplementation in elderly women. PMID- 26846777 TI - Osteoporosis across chronic liver disease. AB - Osteoporosis is a complication of chronic liver disease, with impact on morbidity, quality of life, and survival. The progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with liver disease. So, it is fundamental to make better the quality of life and to prevent complications. Metabolic bone disorders are common complications of chronic liver disease (CLD). Patients with CLD have an increased risk of bone fractures, with significant impact on morbidity, quality of life, and even on survival. Bone diseases, including osteomalacia, osteoporosis, and osteopenia, are frequently observed in many types of liver disease. The pathogenesis of damage and the mechanisms of bone loss are different in relation to the specific liver disease. The relevance of these conditions induced many authors to create a new nosographic entity known as "hepatic osteodystrophy", although this term is rarely used anymore and it is now commonly referred to as osteopenia or osteoporosis associated with chronic liver disease. This review is based on the personal experiences of the authors and upon research done of the available literature on this subject matter. The authors searched the PubMed database for publications containing the term "liver disease" in combination with "bone disease", "hepatic osteodistrophy", "osteoporosis", "osteopenia", "osteomalacia", and "fractures". They selected publications from the past 10 years but did not exclude older seminal publications, especially for colestatic liver diseases. This review of literature shows that osteoporosis crosses all CLD. It is important to underline that the progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with CLD. It is fundamental to make better the quality of life and it is mandatory to prevent complications and in particular the osteoporotic ones, especially fractures. PMID- 26846778 TI - Influence of prenatal maternal stress on umbilical cord blood cytokine levels. AB - PURPOSE: Prenatal maternal stress (PNMS) is known to influence fetal programming and development. Thus far, the effects of PNMS on the developing immune system have mainly been documented in animal studies. This study aimed to examine the association between PNMS and immune cytokine profiles in the umbilical cord blood of newborn human infants. METHODS: PNMS, including perceived stress, numbers of stressful life events experiences (both partner and health related), and state and trait anxiety, was assessed with five questionnaires and interviews from 43 pregnant women during the second trimester. Seven key cytokines important for immune function, i.e., IL-12, IL-1beta, IL-4, IL-5, IL-6, IL-8, and TNF-alpha, were analyzed in cord blood by bead-based ELISA method (Luminex 200). Logistic regression was used to estimate the associations of PNMS scores and cytokine levels. RESULTS: Increased levels of IL-1beta, IL-4, IL-5, IL-6, and IL-8 were significantly associated with at least one of the maternal stress assessments, while the levels of IL-12 and TNF-alpha were not significantly associated with any of the PNMS measurements examined. CONCLUSION: These preliminary findings suggest that PNMS may influence cytokine levels in newborn infants, in particular Th2-related cytokines. This report supports previous findings in animal studies and could suggest that newborns born to mothers with elevated PNMS have a predisposition to immune-related disorders. PMID- 26846779 TI - Encountering aged care: a mixed methods investigation of medical students' clinical placement experiences. AB - BACKGROUND: Residential aged care is an increasingly important health setting due to population ageing and the increase in age-related conditions, such as dementia. However, medical education has limited engagement with this fast growing sector and undergraduate training remains primarily focussed on acute presentations in hospital settings. Additionally, concerns have been raised about the adequacy of dementia-related content in undergraduate medical curricula, while research has found mixed attitudes among students towards the care of older people. This study explores how medical students engage with the learning experiences accessible in clinical placements in residential aged care facilities (RACFs), particularly exposure to multiple comorbidity, cognitive impairment, and palliative care. METHODS: Fifth-year medical students (N = 61) completed five-day clinical placements at two Australian aged care facilities in 2013 and 2014. The placements were supported by an iterative yet structured program and academic teaching staff to ensure appropriate educational experiences and oversight. Mixed methods data were collected before and after the clinical placement. Quantitative data included surveys of dementia knowledge and questions about attitudes to the aged care sector and working with older adults. Qualitative data were collected from focus group discussions concerning medical student expectations, learning opportunities, and challenges to engagement. RESULTS: Pre-placement surveys identified good dementia knowledge, but poor attitudes towards aged care and older adults. Negative placement experiences were associated with a struggle to discern case complexity and a perception of an aged care placement as an opportunity cost associated with reduced hospital training time. Irrespective of negative sentiment, post-placement survey data showed significant improvements in attitudes to working with older people and dementia knowledge. Positive student experiences were explained by in-depth engagement with clinically challenging cases and opportunities to practice independent clinical decision making and contribute to resident care. CONCLUSIONS: Aged care placements can improve medical student attitudes to working with older people and dementia knowledge. Clinical placements in RACFs challenge students to become more resourceful and independent in their clinical assessment and decision-making with vulnerable older adults. This suggests that aged care facilities offer considerable opportunity to enhance undergraduate medical education. However, more work is required to engender cultural change across medical curricula to embed issues around ageing, multiple comorbidity, and dementia. PMID- 26846781 TI - A web-based data visualization tool for the MIMIC-II database. AB - BACKGROUND: Although MIMIC-II, a public intensive care database, has been recognized as an invaluable resource for many medical researchers worldwide, becoming a proficient MIMIC-II researcher requires knowledge of SQL programming and an understanding of the MIMIC-II database schema. These are challenging requirements especially for health researchers and clinicians who may have limited computer proficiency. In order to overcome this challenge, our objective was to create an interactive, web-based MIMIC-II data visualization tool that first-time MIMIC-II users can easily use to explore the database. RESULTS: The tool offers two main features: Explore and Compare. The Explore feature enables the user to select a patient cohort within MIMIC-II and visualize the distributions of various administrative, demographic, and clinical variables within the selected cohort. The Compare feature enables the user to select two patient cohorts and visually compare them with respect to a variety of variables. The tool is also helpful to experienced MIMIC-II researchers who can use it to substantially accelerate the cumbersome and time-consuming steps of writing SQL queries and manually visualizing extracted data. CONCLUSIONS: Any interested researcher can use the MIMIC-II data visualization tool for free to quickly and conveniently conduct a preliminary investigation on MIMIC-II with a few mouse clicks. Researchers can also use the tool to learn the characteristics of the MIMIC-II patients. Since it is still impossible to conduct multivariable regression inside the tool, future work includes adding analytics capabilities. Also, the next version of the tool will aim to utilize MIMIC-III which contains more data. PMID- 26846780 TI - Fusion with stem cell makes the hepatocellular carcinoma cells similar to liver tumor-initiating cells. AB - BACKGROUND: Cell fusion is a fast and highly efficient technique for cells to acquire new properties. The fusion of somatic cells with stem cells can reprogram somatic cells to a pluripotent state. Our research on the fusion of stem cells and cancer cells demonstrates that the fused cells can exhibit stemness and cancer cell-like characteristics. Thus, tumor-initiating cell-like cells are generated. METHODS: We employed laser-induced single-cell fusion technique to fuse the hepatocellular carcinoma cells and human embryonic stem cells (hESC). Real-time RT-PCR, flow cytometry and in vivo tumorigenicity assay were adopted to identify the gene expression difference. RESULTS: We successfully produced a fused cell line that coalesces the gene expression information of hepatocellular carcinoma cells and stem cells. Experimental results showed that the fused cells expressed cancer and stemness markers as well as exhibited increased resistance to drug treatment and enhanced tumorigenesis. CONCLUSIONS: Fusion with stem cells transforms liver cancer cells into tumor initiating-like cells. Results indicate that fusion between cancer cell and stem cell may generate tumor initiating-like cells. PMID- 26846782 TI - Expression of HIF-1alpha and HIF-2alpha correlates to biological and clinical significance in papillary thyroid carcinoma. AB - BACKGROUND: The aim of this study was to detect the expression of hypoxia inducible factor (HIF)-1alpha and HIF-2alpha in papillary thyroid carcinoma (PTC) compared with normal thyroid tissues. METHODS: The mRNA levels and protein levels of HIF-1alpha and HIF-2alpha were detected by real-time PCR and Western blot separately in 30 pairs of PTCs and normal thyroid cases. The protein levels were also detected by immunohistochemistry (IHC) using 92 samples of PTC group and 46 normal samples as control group for analyzing the biological and clinical significance of the expression of HIF-1alpha/HIF-2alpha. RESULTS: Real-time PCR results showed the mRNA level of HIF-1alpha and HIF-2alpha were significantly higher in PTC than normal group (P<0.001). Also, significantly higher positive rates (73%/65%) of HIF-1alpha and HIF-2alpha were observed in PTC compared with the control group (27%/35%) by IHC (P<0.01); the consistent results were gotten with Western blot. Although we did not find a significant correlation between the expression of HIF-1alpha and HIF-2alpha with gender, age, calcification, or Hashimoto's disease in the present study (P>0.05), both of their expressions were correlated to lymph node metastasis (P<0.05), capsular invasion (P<0.05), and TNM stage (P<0.05). CONCLUSIONS: Overexpression of HIF-1alpha and HIF-2alpha are associated with the carcinogenesis of PTC, served as potential biomarkers of PTC. PMID- 26846783 TI - Context-dependent mechanisms modulating aldosterone signaling in the kidney. AB - The aldosterone-mineralocorticoid receptor (MR) system serves as the major regulator of fluid homeostasis, and is an important drug target for the treatment of hypertension, heart failure, and chronic kidney disease. While the ligand aldosterone plays a central role in facilitating MR activity, recent studies have revealed that MR signaling is modulated through distinct mechanisms at the levels of the receptor and the downstream targets. Notably, phosphorylation of the ligand-binding domain in MR regulates the ability of the receptor to bind to ligand in renal intercalated cells, providing an additional layer of regulation that allows the cell-selective control of MR signaling. These mechanisms are involved in the context-dependent effects of aldosterone in the distal nephron. In this article, the recent progress in the understanding of mechanisms regulating the action of aldosterone is discussed, focusing on the connecting tubules and collecting duct in the kidney. PMID- 26846784 TI - Association of apoptosis inhibitor of macrophage (AIM) expression with urinary protein and kidney dysfunction. AB - BACKGROUND: Apoptosis inhibitor of macrophage (AIM) expressed on macrophages prolongs inflammation by protecting macrophages from apoptosis. Most circulating AIM co-exists with immunoglobulin M (IgM). AIM's pathophysiological role in relation to IgM remains unclear. Here we evaluated the glomerular expression/deposition of AIM and IgM in the kidney using immunohistochemistry and its associations with clinical manifestations in 43 patients with biopsy confirmed kidney diseases. METHODS: Kidney biopsy tissue from all patients was immunostained for AIM and IgM. Staining patterns and percent stained areas within the glomeruli were determined. Cells expressing AIM were identified by co staining with macrophage and endothelial cell surface markers. Correlations between staining results and clinical parameters were evaluated using univariate and multivariate analyses. RESULTS: AIM was deposited in various areas, such as mesangial and capillary area. A part of AIM expression was localized to CD68 positive macrophages in the glomerulus. Amount of glomerular expression was positively correlated with urinary protein in patients with severe proteinuria (urinary protein >=0.5 g/day) and kidney dysfunction [estimated glomerular filtration ratio (eGFR) <60 ml/min/1.73 m2]. Urinary protein was higher in patients exhibiting overlapping glomerular expression of AIM and IgM. Annual eGFR decline rate negatively correlated with AIM-positive area. AIM-positive area and initial serum creatinine were independently associated with decreased kidney function. CONCLUSION: AIM expression in the kidney was associated with urinary protein and decline in kidney function. Co-expression with IgM appeared to exacerbate AIM's deleterious effects on kidney function. Combined glomerular AIM and IgM expression is a candidate prognostic index for kidney disease. PMID- 26846785 TI - Role of Inflammation and Immunity in Hypertension: Recent Epidemiological, Laboratory, and Clinical Evidence. AB - Inflammation has been shown to play an important role in the mechanisms involved in the pathogenesis of hypertension. Accordingly, innate and adaptive immune responses participate in blood pressure elevation. Here, we describe recent immunity studies focusing on novel inflammatory mechanisms during the hypertensive process. Different subpopulations of cells involved in innate and adaptive immune responses, such as monocyte/macrophages and dendritic cells on the one hand and B and T lymphocytes on the other hand, play roles leading to vascular injury in hypertension. Innate lymphoid cells, including natural killer cells and gamma/delta T cells, have recently been demonstrated to participate in hypertensive mechanisms triggering vascular inflammation. In summary, we discuss the evidence of interaction of these different inflammatory and immune components in both experimental models and in humans during the development of hypertension. PMID- 26846786 TI - Assessment of kidney function in preterm infants: lifelong implications. AB - This educational review will highlight the historical and contemporary references that establish a basic understanding of measurements of kidney function in the neonate and its relevance for the life of an individual. Importantly, the differential renal function of preterm infants relative to term infants has become paramount with the increased viability of preterm infants and the realization that kidney function is associated with gestational age. Moreover, neonatal kidney function is primarily associated with absolute renal mass and hemodynamic stability. Neonatal kidney function and its early developmental progression predict lifelong cardiovascular and renal disease risks. Validation of estimation equations of kidney function in this population has provided important reference data for other investigations and a clinical basis for prospective and longitudinal follow-up. Future research should be directed towards a better understanding of surrogate markers of kidney function from infancy through adulthood. Pediatric nephrologists should be aware of the developmental aspects of kidney function including the importance of the congenital nephron endowment and the preservation of kidney function throughout a lifetime. * Nephrogenesis occurs in utero in concert with other organ systems by branching morphogenesis, including the lungs, pancreas, and vascular tree, with over 60 % of nephrons being formed during the last trimester. * Infants born preterm before 36 weeks' gestation are in active nephrogenesis and are at increased risk of having a decreased nephron endowment from prenatal and postnatal genetic and epigenetic hazards that will impact the patient for a lifetime. * Post-natal adaptation of kidney function is directly proportional to the number of perfused nephrons, estimated by total kidney volume (TKV), mean arterial pressure (MAP), and gestational age. * Accurate measurement of glomerular filtration rate (GFR) in infants is problematic due to the unavailability of the gold standard inulin. The traditional use of creatinine to estimate GFR is unreliable in preterm infants due to its tubular reabsorption by immature kidneys and its dependence on muscle mass as an endogenous marker. Alternative endogenous markers to estimate GFR are cystatin C and beta trace protein (BTP). * Long-term follow-up of renal function in those born preterm should be life long and should include assessment of GFR, total kidney volume (TKV) relative to body surface area (BSA), and cardiovascular risks including hypertension and vascular stiffness. PMID- 26846787 TI - Differences in clinical findings, pathology, and outcomes between C3 glomerulonephritis and membranoproliferative glomerulonephritis. AB - BACKGROUND: To clarify the clinical manifestations of pediatric complement component C3 glomerulonephritis (C3GN), we retrospectively evaluated differences in the clinicopathological findings and prognosis between C3GN and immune-complex mediated membranoproliferative glomerulonephritis (IC-MPGN). METHODS: Thirty seven patients diagnosed with "idiopathic MPGN" were enrolled in this retrospective study. The patients were divided into two groups, with Group 1 consisting of 19 patients diagnosed with IC-MPGN and Group 2 consisting of 18 patients diagnosed with C3GN. The clinical findings and the prognosis were investigated for both groups. RESULTS: Thirteen patients in Group 2 were identified by mandatory annual school screening for urinary abnormalities. The incidence of macro-hematuria and the frequency of low serum C4 values were lower in Group 2 patients than in Group 1 patients. At the time of the second renal biopsy, urinary protein excretion, incidence of hematuria, frequency of low serum C3 values, and scores for mesangial proliferation, glomerular sclerosis, and interstitial fibrosis were higher in Group 2 patients than in Group 1 patients. At the most recent follow-up examination, the number of patients categorized as non-responding or with end-stage renal disease was higher in Group 2 patients than in Group 1 patients. CONCLUSIONS: Our results suggest that the treatment response and prognosis of patients with C3GN are worse than those of patients with IC-mediated MPGN. Therefore, in the clinical context regarding treatment options and prognosis, it may be useful to classify idiopathic MPGN as C3GN or IC MPGN. In addition, long-term follow-up of C3GN is necessary. PMID- 26846788 TI - New approaches to achieve high level enzyme production in Streptomyces lividans. AB - BACKGROUND: Actinomycetes are saprophytic soil bacteria, and a rich source of industrial enzymes. While some of these enzymes can be produced using well characterized production platforms such as Escherichia coli or Bacillus subtilis, Streptomyces lividans may be the preferred host for proper folding and efficient secretion of active enzymes. A combination of promoters, signal peptides and hosts were tested in order to obtain the best protein expression in this actinomycete. The xylanase, Xys1, from S. halstedii, the alpha-amylase, Amy, from S. griseus and the small laccase, SLAC, from S. coelicolor were used as reporters. RESULTS: The promoters xysAp from S. halstedii JM8 and pstSp from S. lividans were the most efficient among those tested. An improvement of 17 % was obtained in xylanase activity when the signal peptide of the alpha-amylase protein (Amy) of S. griseus IMRU3570 was used to direct its secretion. Enhanced expression of SsgA, a protein that plays a role in processes that require cell wall remodelling, resulted in a improvement of 40 and 70 % of xylanase and amylase production, respectively. Deletion of genes SLI7232 and SLI4452 encoding putative repressors of xysAp provided improvement of production up to 70 % in the SLI7232 deletion strain. However, full derepression of this promoter activity was not obtained under the conditions assayed. CONCLUSIONS: Streptomyces lividans is a frequently used platform for industrial enzyme production and a rational strain development approach delivered significant improvement of protein production by this host. PMID- 26846790 TI - Controllable one-pot synthesis of a nest-like Bi2WO6/BiVO4 composite with enhanced photocatalytic antifouling performance under visible light irradiation. AB - In this study, a novel visible-light-sensitive Bi2WO6/BiVO4 composite photocatalyst was controllably synthesized through a facile one-pot hydrothermal method. The Bi2WO6/BiVO4 composite exhibited a perfect nest-like hierarchical microsphere structure, which was constructed by the self-assembly of nanoplates with the assistance of polyvinylpyrrolidone (PVP). The growth mechanism of the Bi2WO6/BiVO4 composite and the effect of its structure on its photocatalytic performance was investigated and proposed. Experimental results showed that the Bi2WO6/BiVO4 composites displayed enhanced photocatalytic antifouling activities under visible light irradiation compared to pure Bi2WO6 and BiVO4. Bi2WO6/BiVO4-1 exhibited the best photocatalytic antifouling performance, and almost all (99.99%) Pseudomonas aeruginosa (P. aeruginosa), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria were killed within 30 min. Moreover, the Bi2WO6/BiVO4-1 composite exhibited excellent stability and reusability in the cycled experiments. The photocatalytic antifouling mechanism was proposed based on the active species trapping experiments, revealing that the photo-induced holes (h(+)) and hydroxyl radicals (OH) could attack the cell wall and cytoplasmic membrane directly and lead to the death of bacteria. The obviously enhanced photocatalytic activity of the Bi2WO6/BiVO4-1 composite could be mainly attributed to the formation of heterojunctions, accelerating the separation of photo-induced electrons and holes. Furthermore, the large BET surface area combined with the wide photoabsorption region further improved the photocatalytic performance of the Bi2WO6/BiVO4-1 composite. This study provides a new strategy to develop novel composite photocatalysts with enhanced photocatalytic performance for marine antifouling and water purification. PMID- 26846789 TI - A review of methods and tools to assess the implementation of government policies to create healthy food environments for preventing obesity and diet-related non communicable diseases. AB - BACKGROUND: Policies to create healthy food environments are recognized as critical components of efforts to prevent obesity and diet-related non communicable diseases. There has not been a systematic review of existing methods and tools used to assess the implementation of these government policies. The purpose of this study was to review methods and tools used for assessing the implementation of government policies to create healthy food environments. The study conducted a systematic literature search. Multiple databases as well as the grey literature were searched. All study designs and review papers on assessing the implementation of government policies to create healthy food environments were included. A quality assessment of the methods and tools identified from relevant studies was carried out using the following four criteria: comprehensiveness, relevance, generalizability and feasibility. This quality assessment was completed by two independent reviewers. RESULTS: The review identified 52 studies across different policy areas, levels and settings. Self administered questionnaires and policy checklists were most commonly applied to assess the extent of policy implementation, whereas semi-structured interviews were most commonly used to evaluate the implementation process. Measures varied widely, with the existence of policy implementation the aspect most commonly assessed. The most frequently identified barriers and facilitators for policy implementation were infrastructure support, resources and stakeholder engagement. The assessment of policy implementation on food environments was usually undertaken in combination with other policy areas, particularly nutrition education and physical activity. Three tools/methods were rated 'high' quality and 13 tools/methods received 'medium' quality ratings. CONCLUSIONS: Harmonization of the available high-quality methods and tools is needed to ensure that assessment of government policy implementation can be compared across different countries and settings and over time. This will contribute to efforts to increase government accountability for their actions to improve the healthiness of food environments. PMID- 26846791 TI - Seasonal variations in fatigue in persons with rheumatoid arthritis: a longitudinal study. AB - BACKGROUND: Fatigue is a prominent symptom in persons with rheumatoid arthritis (RA). Although this symptom has been described to vary in duration and frequency little is known about fluctuations in fatigue over time and season. The aim of this study was to describe monthly and seasonal variations in fatigue, in persons with RA of working age. METHODS: Sixty-five participants diagnosed with RA and aged 20-65 years were recruited from a rheumatology clinic in Sweden. The participants provided self-assessments of their fatigue at seven time points during the four seasons using a 0-100 mm visual analogue scale (VAS) and the Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ). Multiple regression analysis using mixed models was used to analyze changes in fatigue over time. RESULTS: The mean +/- SD of fatigue rated on the VAS was 51 +/ 13, indicating substantial fatigue. Analysis of monthly variation showed statistically significant variation in fatigue ratings concerning VAS fatigue score (p < 0.01) as well as the BRAF-MDQ total score and Living, Cognition (p < 0.001), and Physical (p < 0.05) sub-scores, but not the BRAF-MDQ Emotional sub score. The greatest variations were seen from January to September, with higher fatigue ratings in January. The changes in VAS fatigue scores over time were considered to be of clinical importance. Analysis of seasonal variation revealed a statistically significant seasonal variation in fatigue levels, with higher fatigue values during the winter as measured by VAS fatigue score (p < 0.01) as well as BRAF-MDQ total score (p < 0.01) and Physical and Living sub-scores (both p < 0.01). The greatest variation was seen between winter and autumn for VAS fatigue and between winter and summer for BRAF-MDQ total score and Physical and Living sub-scores. There were no statistical differences in fatigue levels, monthly or seasonal, between sexes or age groups. CONCLUSIONS: The majority of rating scales used in this study showed fluctuations in fatigue, general and physical fatigue being significantly greater during the winter. As fatigue is a substantial symptom in many persons with RA, this information is important for rheumatology professionals when dealing with persons with RA in routine care. PMID- 26846793 TI - Application of buccal fat pad-derived stem cells in combination with autogenous iliac bone graft in the treatment of maxillomandibular atrophy: a preliminary human study. AB - Stem cell therapy for the treatment of bone defects is an alternative or adjunct to autologous bone grafting. This study assessed the efficacy of buccal fat pad derived stem cells (BFPSCs) with iliac bone block grafting for the treatment of extensive human alveolar ridge defects. Eight patients with extensive jaw atrophy were selected for this study. The jaws were reconstructed with non-vascularized anterior iliac crest bone blocks. Gaps between the blocks were filled with freeze dried bone granules and covered with a collagen membrane. In the test group (n=4), these granules were seeded with BFPSCs. Cone beam computed tomography scans were used to assess the amount of new bone formed at six sites in each patient. Trephine biopsies of 2-mm were also taken from the graft site during implant placement for histomorphometric analysis. The mean bone width change at the graft site was greater in the test group than in the control group (3.94+/ 1.62mm vs. 3.01+/-0.89mm). New bone formation was 65.32% in the test group versus 49.21% in the control group. The application of BFPSCs in conjunction with iliac bone block grafts may increase the amount of new bone formation and decrease secondary bone resorption in extensively atrophic jaws. PMID- 26846792 TI - Submental island flap reconstruction reduces cost in oral cancer reconstruction compared to radial forearm free flap reconstruction: a case series and cost analysis. AB - BACKGROUND: In Canada, 4,400 cases of oral cancer are diagnosed yearly. Surgical resection is a key component of treatment in many of these cancers. Reconstruction of defects, with the goal of preserving function, is of utmost importance. Several choices are possible for reconstruction of larger defects, including both free and pedicled flaps. Free flap reconstruction is reliable and effective, but requires additional personnel and peri-operative resources. Pedicled flaps remain an important alternative to free flaps, and are less resource intensive. This paper reviews our inaugural experience with the submental island flap (SIF) and compares costs incurred to a matched cohort of oral cancer patients reconstructed with forearm free flaps. METHODS: Charts of patients who underwent SIF and RFFF reconstruction from January 1st 2013 to April 1st 2015 were retrospectively examined. Associated costs were obtained via online database and previously reported costs at the study institution. RESULTS: Mean length of ICU stay in glossectomy RFFF reconstruction was 4.7 days. Only one patient required ICU stay for one night in the SIF group. Mean length of hospital stay was not significantly different in SIF patients vs RFFF patients (12.4 vs 15.4 days, p > 0.05). Mean operative time was significantly lower in the SIF group compared to the RFFF group (347 vs 552 min, p < 0.05). Total mean intraoperative costs were found to be $4780.59 for RFFF operations, versus $2307.94 for SIF. Total mean cost of post-operative stay was $18158.40 in the SIF group and $43617.60 in the RFFF group. Total cost savings were therefore $27931.85 per patient for the SIF group. CONCLUSIONS: We have demonstrated the use of the submental island flap as an alternative to radial forearm free flaps, showing both decreased hospital costs and comparable patient outcomes. Pedicled flaps are making a resurgence in head and neck reconstruction, and the submental island flap offers an excellent alternative to more labour intensive and costly free flap alternatives. PMID- 26846794 TI - Incidence and recovery of neurosensory disturbances after bilateral sagittal split osteotomy in different age groups: a retrospective study of 263 patients. AB - This study aimed to investigate the incidence of neurosensory disturbance (NSD) after bilateral sagittal split osteotomy (BSSO) in different age groups and to assess the probability of sensory recovery in patients aged <19 years, 19-30 years, and >30 years. Hypoaesthesia of the lower lip was assessed subjectively and objectively immediately after BSSO and at 1 week and 1, 6, and 12 months after BSSO. Hypoaesthesia was considered permanent if it was present 1 year after BSSO. The frequency of NSD immediately after surgery was significantly higher in older patients. The cumulative incidence of recovery at 1 year was lower and the mean time to recovery was longer in the older patients, although these differences were not statistically significant. Older age was a significant risk factor for permanent hypoaesthesia, with an incidence of 4.8% per patient aged <19 years, 7.9% per patient aged 19-30 years, and 15.2% per patient aged >30 years. These findings show that the risk of NSD after BSSO is significantly higher in older patients. These results may aid surgeons in preoperative patient counselling and in deciding the optimal age at which to perform BSSO. PMID- 26846795 TI - Is dextrose prolotherapy superior to placebo for the treatment of temporomandibular joint hypermobility? A randomized clinical trial. AB - A randomized clinical trial involving adult patients with bilateral temporomandibular joint (TMJ) hypermobility referred for treatment was implemented. The sample comprised 30 consecutive patients, who were divided randomly into two groups. The TMJ hypermobility was treated with either saline (placebo group) or dextrose injections (study group). The solution was injected into five different TMJ areas in three sessions at monthly intervals. The predictor variable was the treatment technique. The outcome variables were visual analogue scale (VAS) evaluations and maximum inter-incisal opening (MIO). Outcome variables were recorded preoperatively and at 12 months postoperatively. Descriptive and bivariate statistics were computed, and significance was set at a P-value of <0.05. The follow-up sample comprised 26 subjects: 12 in the placebo group and 14 in the study group. Masticatory efficiency increased and general pain complaints and joint sounds decreased significantly in both groups. MIO decreased significantly only in the study group. Insignificant changes in the other parameters were found for both groups. After estimating differences between follow-up and baseline outcomes, the mean change in primary outcome variables showed no statistically significant difference between the two groups. These findings suggest that dextrose prolotherapy is no more effective than placebo treatment for any of the outcome variables of TMJ hypermobility assessed. PMID- 26846796 TI - Stable Borocyclic Radicals via Frustrated Lewis Pair Hydrogenations. AB - The synthesis and isolation of stable main group radicals remains an ongoing challenge. Here we report the application of frustrated Lewis pair chemistry to the synthesis of boron-containing radicals. H2 activation with polyaromatic diones and B(C6F5)3 leads to radical formation in good yields. These radicals are robust; they do not decompose on silica gel or react with O2 and are stable at 35 degrees C under N2 indefinitely. The mechanism of formation is explored experimentally, with support from DFT calculations. EPR and UV/vis spectroscopy as well as cyclic voltammetry data are provided, and the radicals are shown to react with cobaltocenes in one-electron chemical reductions to their corresponding borate anions. PMID- 26846797 TI - Tumor-Targeting Salmonella typhimurium A1-R: An Overview. AB - The present chapter reviews the development of the tumor-targeting amino-acid auxotrophic strain S. typhimurium A1 and the in vivo selection and characterization of the high-tumor-targeting strain S. typhimurium A1-R. Efficacy of S. typhimurium A1-R in nude-mouse models of prostate, breast, pancreatic, and ovarian cancer, as well as sarcoma and glioma in orthotopic mouse models is described. Also reviewed is efficacy of S. typhimurium A1-R targeting of primary bone tumor and lung metastasis of high-grade osteosarcoma, breast-cancer brain metastasis, and experimental breast-cancer bone metastasis in orthotopic mouse models. The efficacy of S. typhimurium A1-R on pancreatic cancer stem cells, on pancreatic cancer in combination with anti-angiogenic agents, as well as on cervical cancer, soft-tissue sarcoma, and pancreatic cancer patient-derived orthotopic xenograft (PDOX) mouse models, is also described. PMID- 26846798 TI - Enhancement of Tumor-Targeted Delivery of Bacteria with Nitroglycerin Involving Augmentation of the EPR Effect. AB - The use of bacteria, about 1 MUm in size, is now becoming an attractive strategy for cancer treatment. Solid tumors exhibit the enhanced permeability and retention (EPR) effect for biocompatible macromolecules such as polymer conjugated anticancer agents, liposomes, and micelles. This phenomenon permits tumor-selective delivery of such macromolecules. We report here that bacteria injected intravenously evidenced a property similar to that can of these macromolecules. Bacteria that can accumulate selectively in tumors may therefore be used in cancer treatment.Facultative or anaerobic bacteria will grow even under the hypoxic conditions present in solid tumors. We found earlier that nitric oxide (NO) was among the most important factors that facilitated the EPR effect via vasodilatation, opening of endothelial cell junction gaps, and increasing the blood flow of hypovascular tumors. Here, we describe the augmentation of the EPR effect by means of nitroglycerin (NG), a commonly used NO donor, using various macromolecular agents in different tumor models. More importantly, we report that NG significantly enhanced the delivery of Lactobacillus casei to tumors after intravenous injection of the bacteria, more than a tenfold increase in bacterial accumulation in tumors after NG treatment. This finding suggests that NG has a potential advantage to enhance bacterial therapy of cancer, and further investigations of this possibility are warranted. PMID- 26846799 TI - Oral Delivery of Tumor-Targeting Salmonella to Treat Cancer in Mice. AB - Tumor-targeting bacteria have been developed as novel anticancer agents recently. To achieve their therapeutic effects, bacteria have conventionally been injected intravenously or intraperitoneally into animals or humans. Here, we describe the oral delivery of tumor-targeting Salmonella for cancer therapy in a mouse tumor model. We detail the experimental procedures for establishing a mouse tumor model, preparing bacterial culture, mouse gavage, and detection of the tumor targeting capability of bacteria administered orally. We also discuss technical notes and provide practical advice that will help the users of this oral delivery model. PMID- 26846800 TI - Microfluidic Device to Quantify the Behavior of Therapeutic Bacteria in Three Dimensional Tumor Tissue. AB - Microfluidic devices enable precise quantification of the interactions between anti-cancer bacteria and tumor tissue. Direct observation of bacterial movement and gene expression in tissue is difficult with either monolayers of cells or tumor-bearing mice. Quantification of these interactions is necessary to understand the inherent mechanisms of bacterial targeting and to develop modified organisms with enhanced therapeutic properties. Here we describe the procedures for designing, printing, and assembling microfluidic tumor-on-a-chip devices. We also describe the procedures for inserting three-dimensional tumor-cell masses, exposure to bacteria, and analyzing the resultant images. PMID- 26846801 TI - Tumor-Targeting Therapy Using Gene-Engineered Anaerobic-Nonpathogenic Bifidobacterium longum. AB - Despite great progress in molecular-targeting drugs for cancer treatment, there are problems of disease recurrence due to cancer-cell resistance to those drugs, derived from the heterogeneity of tumors. On one hand, the low-oxygen microenvironment present in malignant tumor tissues has been regarded as a source of resistance of cancer cells against conventional therapie, such as radiation and chemotherapy. To overcome these problems, we have been developing a system to selectively deliver a large amount of anticancer drugs to malignant tumors by making use of the limiting factor, hypoxia, in tumors. Our strategy is to use hypoxia as a selective target. Here, we show methods and protocols using the nonpathogenic obligate anaerobic Bifidobacterium longum as a drug-delivery system (DDS) to target anaerobic tumor tissue. PMID- 26846802 TI - Noninvasive In Vivo Imaging to Follow Bacteria Engaged in Cancer Therapy. AB - Non-invasive in vivo imaging represents a powerful tool to monitor cellular and molecular processes in the living animal. In the special case of bacteria mediated cancer therapy using bioluminescent bacteria, it opens up the possibility to follow the course of the microorganisms into the tumor via the circulation. The mechanism by which bacteria elicit their anti-tumor potential is not completely understood. However, this knowledge is crucial to improve bacteria as an anti-cancer tool that can be introduced into the clinic. For the study of these aspects, in vivo imaging can be considered a key technology. PMID- 26846804 TI - Employment of Salmonella in Cancer Gene Therapy. AB - One of the primary limitations of cancer gene therapy is lack of selectivity of the therapeutic gene to tumor cells. Current efforts are focused on discovering and developing tumor-targeting vectors that selectively target only cancer cells but spare normal cells to improve the therapeutic index. The use of preferentially tumor-targeting bacteria as vectors is one of the innovative approaches for the treatment of cancer. This is based on the observation that some obligate or facultative-anaerobic bacteria are capable of multiplying selectively in tumors and inhibiting their growth. In this study, we exploited attenuated Salmonella as a tumoricidal agent and a vector to deliver genes for tumor-targeted gene therapy. Attenuated Salmonella, carrying a eukaryotic expression plasmid encoding an anti-angiogenic gene, was used to evaluate its' ability for tumor targeting and gene delivery in murine tumor models. We also investigated the use of a polymer to modify or shield Salmonella from the pre existing immune response in the host in order to improve gene delivery to the tumor. These results suggest that tumor-targeted gene therapy using Salmonella carrying a therapeutic gene, which exerts tumoricidal and anti-angiogenic activities, represents a promising strategy for the treatment of tumors. PMID- 26846803 TI - In Vivo Bioluminescence Imaging of Intratumoral Bacteria. AB - This chapter describes the use of whole-body bioluminescent imaging (BLI) for the study of bacterial trafficking in live mice, with an emphasis on the use of bacteria in therapy of cancer. Bacteria present an attractive class of vector for cancer therapy, possessing a natural ability to grow preferentially within tumors following systemic administration. Bacteria engineered to express the lux gene cassette permit BLI detection of the bacteria and tumor sites concurrently. The location and levels of bacteria within tumors over time can be readily examined, visualized in two or three dimensions. The method is applicable to a wide range of bacterial species and tumor xenograft types. This article describes the protocol for analysis of bioluminescent bacteria within subcutaneous tumor bearing mice. This powerful, and inexpensive, real-time imaging strategy represents an ideal method for the study of bacteria in vivo in the context of cancer research. This protocol outlines the procedure for studying lux-tagged Escherichia coli and Bifidobacterium breve in mice, demonstrating the spatial and temporal readout from 2D and 3D BLI achievable with whole-body in vivo luminescence imaging. PMID- 26846805 TI - Development of a Targeted Gene-Delivery System Using Escherichia coli. AB - A gene-delivery system based on microbes is useful for development of targeted gene therapy of non-phagocytic cancer cells. Here, the feasibility of the delivery system is illustrated by targeted delivery of a transgene (i.e., eukaryotic GFP) by Escherichia coli to HER2/neu-positive cancer cells. An E. coli strain was engineered with surface display of the anti-HER2/neu affibody. To release the gene cargo, a programmed lysis system based on phage phiX174 gene E was introduced into the E. coli strain. As a result, 3 % of HER2/neu-positive cells that were infected with engineered E. coli were able to express the GFP. PMID- 26846807 TI - Determination of Plasmid Segregational Stability in a Growing Bacterial Population. AB - Bacterial plasmids are extensively used as cloning vectors for a number of genes for academic and commercial purposes. Moreover, attenuated bacteria carrying recombinant plasmids expressing genes with anti-tumor activity have shown promising therapeutic results in animal models of cancer. Equitable plasmid distribution between daughter cells during cell division, i.e., plasmid segregational stability, depends on many factors, including the plasmid copy number, its replication mechanism, the levels of recombinant gene expression, the type of bacterial host, and the metabolic burden associated with all these factors. Plasmid vectors usually code for antibiotic-resistant functions, and, in order to enrich the culture with bacteria containing plasmids, antibiotic selective pressure is commonly used to eliminate plasmid-free segregants from the growing population. However, administration of antibiotics can be inconvenient for many industrial and therapeutic applications. Extensive ongoing research is being carried out to develop stably-inherited plasmid vectors. Here, I present an easy and precise method for determining the kinetics of plasmid loss or maintenance for every ten generations of bacterial growth in culture. PMID- 26846806 TI - Isolation and Analysis of Suppressor Mutations in Tumor-Targeted msbB Salmonella. AB - Tumor-targeted Salmonella offers a promising approach to the delivery of therapeutics for the treatment of cancer. The Salmonella strains used, however, must be stably attenuated in order to provide sufficient safety for administration. Approaches to the generation of attenuated Salmonella strains have included deletion of the msbB gene that is responsible for addition of the terminal myristol group to lipid A. In the absence of myristoylation, lipid A is no longer capable of inducing septic shock, resulting in a significant enhancement in safety. However, msbB Salmonella strains also exhibit an unusual set of additional physiological characteristics, including sensitivities to NaCl, EGTA, deoxycholate, polymyxin, and CO2. Suppressor mutations that compensate for these sensitivities include somA, Suwwan, pmrA (C), and zwf. We describe here methods for isolation of strains with compensatory mutations that suppress these types of sensitivities and techniques for determining their underlying genetic changes and analysis of their effects in murine tumor models. PMID- 26846808 TI - Visualization of Anticancer Salmonella typhimurium Engineered for Remote Control of Therapeutic Proteins. AB - Tumor-targeting bacteria are studied for their ability to carry therapeutic molecules to tumors or, when designed as imaging probes, to visualize the infection pathway. The present protocol describes a method to achieve remote control of therapeutic gene expression in bacteria which are also engineered to visualize the therapeutic process. This strategy may increase the safety of bacteria used to deliver therapeutic genes to tumors in vivo. PMID- 26846809 TI - Methods for Tumor Targeting with Salmonella typhimurium A1-R. AB - Salmonella typhimurium A1-R (S. typhimurium A1-R) has shown great preclinical promise as a broad-based anti-cancer therapeutic (please see Chapter 1 ). The present chapter describes materials and methods for the preclinical study of S. typhimurium A1-R in clinically-relevant mouse models. Establishment of orthotopic metastatic mouse models of the major cancer types is described, as well as other useful models, for efficacy studies of S. typhimurium A1-R or other tumor targeting bacteria, as well. Imaging methods are described to visualize GFP labeled S. typhimurium A1-R, as well as GFP- and/or RFP-labeled cancer cells in vitro and in vivo, which S. typhimurium A1-R targets. The mouse models include metastasis to major organs that are life-threatening to cancer patients including the liver, lung, bone, and brain and how to target these metastases with S. typhimurium A1-R. Various routes of administration of S. typhimurium A1-R are described with the advantages and disadvantages of each. Basic experiments to determine toxic effects of S. typhimurium A1-R are also described. Also described are methodologies for combining S. typhimurium A1-R and chemotherapy. The testing of S. typhimurium A1-R on patient tumors in patient-derived orthotopic xenograft (PDOX) mouse models is also described. The major methodologies described in this chapter should be translatable for clinical studies. PMID- 26846810 TI - Salmonella typhimurium A1-R and Cell-Cycle Decoy Therapy of Cancer. AB - Cancer cells in G0/G1 are resistant to cytotoxic chemotherapy agents which kill only cycling cancer cells. Salmonella typhimurium A1-R (S. typhimurium A1-R) decoyed cancer cells in monolayer culture and in tumor spheres to cycle from G0/G1 to S/G2/M, as demonstrated by fluorescence ubiquitination-based cell cycle indicator (FUCCI) imaging. S. typhimurium A1-R targeted FUCCI-expressing subcutaneous tumors, and tumors growing on the liver, growing in nude mice and also decoyed quiescent cancer cells, which were the majority of the cells in the tumors, to cycle from G0/G1 to S/G2/M. The S. typhimurium A1-R-decoyed cancer cells became sensitive to cytotoxic agents. PMID- 26846812 TI - Advances in high throughput DNA sequence data compression. AB - Advances in high throughput sequencing technologies and reduction in cost of sequencing have led to exponential growth in high throughput DNA sequence data. This growth has posed challenges such as storage, retrieval, and transmission of sequencing data. Data compression is used to cope with these challenges. Various methods have been developed to compress genomic and sequencing data. In this article, we present a comprehensive review of compression methods for genome and reads compression. Algorithms are categorized as referential or reference free. Experimental results and comparative analysis of various methods for data compression are presented. Finally, key challenges and research directions in DNA sequence data compression are highlighted. PMID- 26846811 TI - Future of Bacterial Therapy of Cancer. AB - Bacterial therapy of cancer has a centuries-long history and was first-line therapy at the hospital in New York City that would become Memorial Sloan Kettering Cancer Center, under Dr. William B. Coley. However, after Coley's death in 1936, bacterial therapy of cancer ceased in the clinic until the present century. Clinical trials have been recently carried out for strains of the obligate anaerobe Clostridium novyi with the toxin gene deleted, and on an attenuated strain of Salmonella typhimurium (S. typhimurium), which is a facultative anaerobe that can grow in viable, as well as necrotic, areas of tumors, unlike Clostridium, which can only grow in the hypoxic areas. Our laboratory has developed the novel strain S. typhimurium A1-R that is effective against all tumor types in clinically-relevant mouse models, including patient derived orthotopic xenograft (PDOX) mouse models. This chapter suggests future clinical applications for S. typhimurium A1-R. PMID- 26846813 TI - Accurate refinement of docked protein complexes using evolutionary information and deep learning. AB - One of the major challenges for protein docking methods is to accurately discriminate native-like structures from false positives. Docking methods are often inaccurate and the results have to be refined and re-ranked to obtain native-like complexes and remove outliers. In a previous work, we introduced AccuRefiner, a machine learning based tool for refining protein-protein complexes. Given a docked complex, the refinement tool produces a small set of refined versions of the input complex, with lower root-mean-square-deviation (RMSD) of atomic positions with respect to the native structure. The method employs a unique ranking tool that accurately predicts the RMSD of docked complexes with respect to the native structure. In this work, we use a deep learning network with a similar set of features and five layers. We show that a properly trained deep learning network can accurately predict the RMSD of a docked complex with 1.40 A error margin on average, by approximating the complex relationship between a wide set of scoring function terms and the RMSD of a docked structure. The network was trained on 35000 unbound docking complexes generated by RosettaDock. We tested our method on 25 different putative docked complexes produced also by RosettaDock for five proteins that were not included in the training data. The results demonstrate that the high accuracy of the ranking tool enables AccuRefiner to consistently choose the refinement candidates with lower RMSD values compared to the coarsely docked input structures. PMID- 26846814 TI - Prediction of protein-protein interaction network using a multi-objective optimization approach. AB - Protein-Protein Interactions (PPIs) are very important as they coordinate almost all cellular processes. This paper attempts to formulate PPI prediction problem in a multi-objective optimization framework. The scoring functions for the trial solution deal with simultaneous maximization of functional similarity, strength of the domain interaction profiles, and the number of common neighbors of the proteins predicted to be interacting. The above optimization problem is solved using the proposed Firefly Algorithm with Nondominated Sorting. Experiments undertaken reveal that the proposed PPI prediction technique outperforms existing methods, including gene ontology-based Relative Specific Similarity, multi-domain based Domain Cohesion Coupling method, domain-based Random Decision Forest method, Bagging with REP Tree, and evolutionary/swarm algorithm-based approaches, with respect to sensitivity, specificity, and F1 score. PMID- 26846815 TI - Impairment of mitochondrial respiration following ex vivo cyanide exposure in peripheral blood mononuclear cells. AB - OBJECTIVES: The objective of this study is to measure mitochondrial respiration using intact cells from whole blood exposed to cyanide as a new biomarker for mitochondrial inhibition. METHODS: A single nontourniqueted venous blood sample was collected from 10 healthy volunteers after informed consent. Venous lactate was measured immediately following blood collection. Half of the remaining blood sample was then incubated with 100 mM of potassium cyanide (KCN) for 5 min, and half of the sample remained unexposed. Repeat lactate measurements were performed from blood exposed and not exposed to KCN. Measurement of mitochondrial respiration: intact PBMCs were placed in a 2-mL chamber at a final concentration of 2-3 * 10(6) cells/mL. Measurements of oxygen consumption were performed at 37 degrees C in a high-resolution oxygraph (Oxygraph-2k Oroboros Instruments, Innsbruck, Austria). Oxygen flux (in pmol O2/s/10(6) cells), which is directly proportional to oxygen consumption, was recorded continuously using DatLab software 6 (Oroboros Instruments). RESULTS: There were significance differences in the relevant key parameters of mitochondrial respiration: Of the parameters measuring mitochondrial respiration, four of the six demonstrated a statistically significant mean difference between control and cyanide: for routine respiration (mean difference [control-cyanide]: 8.9 pmol O2/s/10(6) cells; 95% CI: 5.6-12.2, p < 0.0001); Proton Leak (mean difference: 0.73 pmol O2/s/10(6) cells; 95% CI: 0.33-1.79, p = 0.157); Maximal respiration (mean difference: 21.7 pmol O2/s/10(6) cells; 95% CI: 16.0-27.6, p < 0.0001); Residual oxygen consumption (mean difference 0.25 pmol O2/s/10(6) cells; 95% CI: -0.68-1.18, p = 0.557). There was a significant difference in spare respiratory capacity (SRC) and adenosine triphosphate (ATP)-linked respiration with the control samples demonstrating a higher SRC and ATP-linked respiration. Finally, there is a statistically significant difference in lactate (mean difference -0.32, 95% CI: -0.41 to -0.23, p < 0.0001), though clinically similar level, with a higher lactate concentration in the cyanide samples. CONCLUSIONS: In this ex vivo model, the measurements of key parameters in mitochondrial respiration may be a more sensitive measure of cellular function when compared to lactate. PMID- 26846816 TI - Characterization of an Inherited Neurologic Syndrome in Toyger Cats with Forebrain Commissural Malformations, Ventriculomegaly and Interhemispheric Cysts. AB - BACKGROUND: In children, frequent congenital malformations with concomitant agenesis of the corpus callosum are diagnosed by neuroimaging in association with other cerebral malformations, including interhemispheric cysts and ventriculomegaly. Similar studies providing full characterization of brain defects by in vivo magnetic resonance imaging (MRI), and correlations with the pertinent anatomic pathologic examinations are absent in veterinary medicine. HYPOTHESIS/OBJECTIVES: Congenital brain defects underlie the neurologic signs observed in Toyger cats selectively bred for a short ear phenotype. ANIMALS: Using proper pedigree analysis and genetic evaluations, 20 related Oriental derived crossbred Toyger cats were evaluated. Seven clinically healthy (carrier) cats and 13 clinically affected cats that had neurologic signs, short ear phenotype and concomitant complex brain anomalies were studied. METHODS: Complete physical and neurologic examinations and MRI were performed in all clinically healthy and affected cats. Postmortem and histopathologic examinations were performed in 8 affected cats and 5 healthy cats. RESULTS: Neurologic and MRI investigations confirmed 13 clinically affected cats with structural brain abnormalities. Ventriculomegaly with frequent concomitant supratentorial interhemispheric, communicating ventricular type-1b cysts and multiple midline and callosal malformations were detected in all cats displaying neurologic signs. Genetic analysis confirmed autosomal recessive mode of inheritance with no chromosomal abnormalities. CONCLUSIONS AND CLINICAL IMPORTANCE: Neuroanatomic dissections and histopathology were helpful for evaluation of abnormalities in midline brain structures, and for the full characterization of cysts. However, MRI was more sensitive for detection of small cysts. In this feline model, MRI diagnosis had extremely good correlation with pathologic abnormalities noted in the subset of animals that were examined by both modalities. PMID- 26846817 TI - Clinical attachment loss: estimation by direct and indirect methods. AB - OBJECTIVE: This observational study aimed to compare the estimation of clinical attachment loss (CAL) as measured by direct (CALD ) and indirect (CALI ) methods. METHODS: Periodontitis patients (n = 75; mean age: 50.9 +/- 8.02 years; 72.2% women; 50.6% smokers) received a periodontal examination (six sites/tooth) to determine the presence of visible plaque and calculus, the gingival bleeding index (GBI), periodontal probing depth (PPD), bleeding on probing (BOP), CALD and gingival recession (GR). CALI values resulted from the sum of PPD and GR values. Statistical analysis considered only data from sites with visible GR (e.g. the gingival margin apical to the cemento-enamel junction; n = 4,757 sites) and determined the mean difference between CALI and CALD measurements. Based on the mean difference, univariate and multivariate analyses were also performed. RESULTS: Mean CALD and CALI values were 3.96 +/- 2.07 mm and 4.47 +/- 2.03 mm, respectively. The indirect method overestimated CAL compared with the direct method (mean difference: 0.51 +/- 1.23 mm; P < 0.001). On uni- and multivariate analyses, absence of GBI and BOP, PPD and proximal site location had significant influences on the overestimation of CAL by the indirect method (all P <= 0.01). The indirect method increased the CAL value by 0.38 mm for each additional 1 mm in PPD. CONCLUSIONS: To decrease the number of probing errors in daily practice it is suggested that direct examination is more appropriate than the indirect method for estimating CAL. PMID- 26846818 TI - ABT-414, an Antibody-Drug Conjugate Targeting a Tumor-Selective EGFR Epitope. AB - Targeting tumor-overexpressed EGFR with an antibody-drug conjugate (ADC) is an attractive therapeutic strategy; however, normal tissue expression represents a significant toxicity risk. The anti-EGFR antibody ABT-806 targets a unique tumor specific epitope and exhibits minimal reactivity to EGFR in normal tissue, suggesting its suitability for the development of an ADC. We describe the binding properties and preclinical activity of ABT-414, an ABT-806 monomethyl auristatin F conjugate. In vitro, ABT-414 selectively kills tumor cells overexpressing wild type or mutant forms of EGFR. ABT-414 inhibits the growth of xenograft tumors with high EGFR expression and causes complete regressions and cures in the most sensitive models. Tumor growth inhibition is also observed in tumor models with EGFR mutations, including activating mutations and those with the exon 2-7 deletion [EGFR variant III (EGFRvIII)], commonly found in glioblastoma multiforme. ABT-414 exhibits potent cytotoxicity against glioblastoma multiforme patient-derived xenograft models expressing either wild-type EGFR or EGFRvIII, with sustained regressions and cures observed at clinically relevant doses. ABT 414 also combines with standard-of-care treatment of radiation and temozolomide, providing significant therapeutic benefit in a glioblastoma multiforme xenograft model. On the basis of these results, ABT-414 has advanced to phase I/II clinical trials, and objective responses have been observed in patients with both amplified wild-type and EGFRvIII-expressing tumors. Mol Cancer Ther; 15(4); 661 9. (c)2016 AACR. PMID- 26846819 TI - Targeting Interleukin-11 Receptor-alpha Impairs Human Endometrial Cancer Cell Proliferation and Invasion In Vitro and Reduces Tumor Growth and Metastasis In Vivo. AB - Endometrial cancer contributes to significant morbidity and mortality in women with advanced stage or recurrent disease. IL11 is a cytokine that regulates cell cycle, invasion, and migration, all hallmarks of cancer. IL11 is elevated in endometrial tumors and uterine lavage fluid in women with endometrial cancer, and alters endometrial epithelial cancer cell adhesion and migration in vitro, but its role in endometrial tumorigenesis in vivo is unknown. We injected mice subcutaneously with human-derived Ishikawa or HEC1A endometrial epithelial cancer cells (ectopic), or HEC1A cells into the uterus (orthotopic) to develop endometrial cancer mouse models. Administration of anti-human IL11 receptor (R) alpha blocking antibody dramatically reduced HEC1A-derived tumor growth in both models and reduced peritoneal metastatic lesion spread in the orthotopic model, compared with IgG. Anti-human IL11Ralpha retained a well-differentiated, endometrial epithelial phenotype in the HEC1A ectopic mice, suggesting it prevented epithelial-to-mesenchymal transition. Blockade of mouse IL11Ralpha with anti-mouse IL11Ralpha antibody did not alter tumor growth, suggesting that cancer epithelial cell IL11 signaling is required for tumor progression. In vitro, anti human IL11Ralpha antibody significantly reduced Ishikawa and HEC1A cell proliferation and invasion and promoted apoptosis. Anti-human, but not anti mouse, IL11Ralpha antibody reduced STAT3, but not ERK, activation in HEC1A cells in vitro and in endometrial tumors in xenograft mice. We demonstrated that targeted blockade of endometrial cancer epithelial cell IL11 signaling reduced primary tumor growth and impaired metastasis in ectopic and orthotopic endometrial cancer models in vivo Our data suggest that therapeutically targeting IL11Ralpha could inhibit endometrial cancer growth and dissemination. Mol Cancer Ther; 15(4); 720-30. (c)2016 AACR. PMID- 26846820 TI - Effective Concentration of a Multikinase Inhibitor within Bone Marrow Correlates with In Vitro Cell Killing in Therapy-Resistant Chronic Myeloid Leukemia. AB - Leukemia cells escape BCR-ABL-targeted therapy by developing mutations, such as T315I, in the p210(BCR-ABL) fusion protein in Philadelphia chromosome-positive chronic myeloid leukemia (CML). Although most effort has been focused on development of new tyrosine kinase inhibitors, enrichment of these small-molecule inhibitors in the tumor tissue can also have a profound impact on treatment outcomes. Here, we report that a 2-hour exposure of the T315I-mutant CML cells to 10 MUmol/L of the multikinase inhibitor TG101209 suppressed BCR-ABL-independent signaling and caused cell-cycle arrest at G2-M. Further increase in drug concentration to 17.5 MUmol/L blocked phosphorylation of the mutant BCR-ABL kinase and its downstream JAK2 and STAT5. The effective dosage to overcome therapy resistance identified in an in vitro setting serves as a guidance to develop the proper drug formulation for in vivo efficacy. A targeted formulation was developed to achieve sustained bone marrow TG101209 concentration at or above 17.5 MUmol/L for effective killing of CML cells in vivo Potent inhibition of leukemia cell growth and extended survival were observed in two murine models of CML treated with 40 mg/kg intravenously administered targeted TG101209, but not with the untargeted drug at the same dosage. Our finding provides a unique approach to develop treatments for therapy-resistant CML. Mol Cancer Ther; 15(5); 899-910. (c)2016 AACR. PMID- 26846821 TI - Feasibility of an Orthogonal Redundant Sensor incorporating Optical plus Redundant Electrochemical Glucose Sensing. AB - BACKGROUND: Orthogonal redundancy for glucose sensing (multiple sensing elements utilizing distinct methodologies) may enhance performance compared to nonredundant sensors, and to sensors with multiple elements utilizing the same technology (simple redundancy). We compared the performance of a prototype orthogonal redundant sensor (ORS) combining optical fluorescence and redundant electrochemical sensing via a single insertion platform to an electrochemical simple redundant sensor (SRS). METHODS: Twenty-one adults with type 1 diabetes wore an ORS and an SRS concurrently for 7 days. Following sensor insertion, and on Day 4 with a standardized meal, frequent venous samples were collected for reference glucose measurement (laboratory [YSI] and meter) over 3 and 4 hours, respectively. Between study visits reference capillary blood glucose testing was undertaken. Sensor data were processed prospectively. RESULTS: ORS mean absolute relative difference (MARD) was (mean +/- SD) 10.5 +/- 13.2% versus SRS 11.0 +/- 10.4% (P = .34). ORS values in Clarke error grid zones A and A+B were 88.1% and 97.6%, respectively, versus SRS 86.4% and 97.8%, respectively (P = .23 and P = .84). ORS Day 1 MARD (10.7 +/- 10.7%) was superior to SRS (16.5 +/- 13.4%; P < .0001), and comparable to ORS MARD for the week. ORS sensor survival (time averaged mean) was 92.1% versus SRS 74.4% (P = .10). ORS display time (96.0 +/- 5.8%) was equivalent to SRS (95.6 +/- 8.9%; P = .87). CONCLUSIONS: Combining simple and orthogonal sensor redundancy via a single insertion is feasible, with accuracy comparing favorably to current generation nonredundant sensors. Addition of an optical component potentially improves sensor reliability compared to electrochemical sensing alone. Further improvement in optical sensing performance is required prior to clinical application. PMID- 26846822 TI - Impact of obstructive sleep apnoea on insulin resistance in nonobese and obese children. AB - Obstructive sleep apnoea (OSA) has been inconsistently associated with insulin resistance and adverse metabolic states. We aimed to assess independent contributions of OSA to insulin resistance and dyslipidaemia in a large paediatric cohort.Habitually snoring children underwent overnight polysomnography, anthropometric measurements and fasting laboratory evaluations. Primary outcome measures included insulin, glucose, homeostasis model of insulin resistance, lipoproteins and sleep disturbance measures.Among 459 children aged 5 12 years, obesity was the primary driver of most associations between OSA and metabolic measures, but sleep duration was inversely associated with glucose levels, with N3 and rapid eye movement (REM) sleep being negatively associated and sleep fragmentation positively associated with insulin resistance measures. In children with mild OSA, the presence of obesity increased the odds for insulin resistance, while higher apnoea/hypopnoea index values emerged among obese children who were more insulin-resistant.The exclusive presence of interactions between OSA and obesity in the degree of insulin resistance is coupled with synergistic contributions by sleep fragmentation to insulin resistance in the context of obesity. Insufficient N3 or REM sleep may also contribute to higher glycaemia independently of obesity. Studies are needed to better delineate the roles of puberty and sleep fragmentation in insulin resistance and the metabolic syndrome. PMID- 26846823 TI - Should all adult cystic fibrosis patients with repeated nontuberculous mycobacteria cultures receive specific treatment? A 10-year case-control study. PMID- 26846825 TI - High levels of neurological involvement but low mortality in miliary tuberculosis: a 6-year case-series from the UK. PMID- 26846824 TI - Sputum inflammatory cells in COPD patients classified according to GOLD 2011 guidelines. PMID- 26846826 TI - Does mass spectrometric breath analysis detect Pseudomonas aeruginosa in cystic fibrosis? PMID- 26846827 TI - Blood eosinophil count to predict bronchial eosinophilic inflammation in COPD. PMID- 26846828 TI - Modafinil/armodafinil in obstructive sleep apnoea: a systematic review and meta analysis. AB - Modafinil is used internationally to treat residual sleepiness despite continuous positive airway pressure in obstructive sleep apnoea (res-OSA). In 2011, the European Medicines Agency removed the indication based on an unfavourable risk benefit profile in two trials for efficacy and all accumulated safety data. We performed a meta-analysis of all randomised controlled trials of modafinil (or armodafinil) in res-OSA to quantify efficacy and safety.We systematically searched and assessed studies from major databases, conferences and trials registries to find randomised, placebo-controlled trials of modafinil/armodafinil for >=2 weeks in adult res-OSA treating sleepiness.We analysed 10 of the 232 articles identified that met inclusion criteria (1466 patients). Modafinil/armodafinil improved the Epworth Sleepiness Scale score (2.2 points, 95% CI 1.5-2.9) and the Maintenance of Wakefulness Test over placebo (3 min, 95% CI 2.1-3.8 min). Modafinil/armodafinil tripled adverse events and doubled adverse events leading to withdrawal but did not increase serious adverse events (hospitalisations or death).Modafinil and armodafinil improve subjective and objective daytime sleepiness in res-OSA. We believe our analysis is a fairer analysis of the risk-benefit profile of this indication. Clinicians may want to use this data to balance the risks and benefits on a case-by-case basis with their patients. PMID- 26846830 TI - The emerging role of myeloid-derived suppressor cells in lung diseases. AB - Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterised by their potential to control T-cell responses and to dampen inflammation. While the role of MDSCs in cancer has been studied in depth, our understanding of their relevance for infectious and inflammatory disease conditions has just begun to evolve. Recent studies highlight an emerging and complex role for MDSCs in pulmonary diseases. In this review, we discuss the potential contribution of MDSCs as biomarkers and therapeutic targets in lung diseases, particularly lung cancer, tuberculosis, chronic obstructive pulmonary disease, asthma and cystic fibrosis. PMID- 26846829 TI - Tuberculosis in migrants from 106 countries to Italy, 2008-2014. PMID- 26846831 TI - The lived experience with idiopathic pulmonary fibrosis: a qualitative study. AB - The disease course in idiopathic pulmonary fibrosis (IPF) is variable, but patients experience a progressive decline in lung function and increased symptom burden leading to death. Little is known about the patients' experience and their needs during the disease course or about the burden on family caregivers. Both patients and family caregivers face an altered life as the disease progresses. The aim of our study was to increase knowledge of life with IPF for patients and family caregivers.This study had a qualitative descriptive design using in-depth dyadic interviews with IPF patients (n=25) and family caregivers (n=24). We used the five-step analysis from the framework method and analysed the data on three levels: the patient, the family caregivers and couple level.The following six themes emerged as the main results: information and disclosure, reactional dyssynchrony, perpetual vigilance, emotional ambivalence, gradual and tacit role shift, and adapted coping strategies.Our findings suggest that IPF patients need information at the time of diagnosis, but some issues should be paced as the disease progresses. A palliation plan was demanded by patients and their caregivers. Further efforts are required to provide palliative care to IPF patients starting at the time of diagnosis. PMID- 26846833 TI - Clinical phenotypes in adult patients with bronchiectasis. AB - Bronchiectasis is a heterogeneous disease. This study aimed at identifying discrete groups of patients with different clinical and biological characteristics and long-term outcomes.This was a secondary analysis of five European databases of prospectively enrolled adult outpatients with bronchiectasis. Principal component and cluster analyses were performed using demographics, comorbidities, and clinical, radiological, functional and microbiological variables collected during the stable state. Exacerbations, hospitalisations and mortality during a 3-year follow-up were recorded. Clusters were externally validated in an independent cohort of patients with bronchiectasis, also investigating inflammatory markers in sputum.Among 1145 patients (median age 66 years; 40% male), four clusters were identified driven by the presence of chronic infection with Pseudomonas aeruginosaor other pathogens and daily sputum: "Pseudomonas" (16%), "Other chronic infection" (24%), "Daily sputum" (33%) and "Dry bronchiectasis" (27%). Patients in the four clusters showed significant differences in terms of quality of life, exacerbations, hospitalisations and mortality during follow-up. In the validation cohort, free neutrophil elastase activity, myeloperoxidase activity and interleukin-1beta levels in sputum were significantly different among the clusters.Identification of four clinical phenotypes in bronchiectasis could favour focused treatments in future interventional studies designed to alter the natural history of the disease. PMID- 26846832 TI - Fractional exhaled nitric oxide for the management of asthma in adults: a systematic review. AB - The aim of this review was to evaluate the clinical effectiveness of fractional exhaled nitric oxide (FeNO) measured in a clinical setting for the management of asthma in adults.13 electronic databases were searched and studies were selected against predefined inclusion criteria. Quality assessment was conducted using QUADAS-2. Class effect meta-analyses were performed.Six studies were included. Despite high levels of heterogeneity in multiple study characteristics, exploratory class effect meta-analyses were conducted. Four studies reported a wider definition of exacerbation rates (major or severe exacerbation) with a pooled rate ratio of 0.80 (95% CI 0.63-1.02). Two studies reported rates of severe exacerbations (requiring oral corticosteroid use) with a pooled rate ratio of 0.89 (95% CI 0.43-1.72). Inhaled corticosteroid use was reported by four studies, with a pooled standardised mean difference of -0.24 (95% CI -0.56-0.07). No statistically significant differences for health-related quality of life or asthma control were found.FeNO guided management showed no statistically significant benefit in terms of severe exacerbations or inhaled corticosteroid use, but showed a statistically significant reduction in exacerbations of any severity. However, further research is warranted to clearly define which management protocols (including cut-off points) offer best efficacy and which patient groups would benefit the most. PMID- 26846834 TI - Description of a randomised controlled trial of inhaled corticosteroid/fast-onset LABA reliever therapy in mild asthma. PMID- 26846835 TI - Interleukin-22 receptor is overexpressed in nonsmall cell lung cancer and portends a poor prognosis. PMID- 26846836 TI - Pulmonary artery size as a predictor of outcomes in idiopathic pulmonary fibrosis. AB - IPF patients have heightened propensity for pulmonary hypertension, which portends a worse outcome. Presence of pulmonary hypertension may be reflected in an enlarged pulmonary artery. We investigated pulmonary artery size measured on high-resolution computed tomography (HRCT) as an outcome predictor in IPF.We retrospectively reviewed all IPF patients evaluated at a tertiary-care centre between 2008 and 2013. Pulmonary artery and ascending aorta diameters were measured from chest HRCT with pulmonary artery:ascending aorta diameter (PA:A) ratio calculations. Outcome analysis defined by either death or lung transplant based on pulmonary artery size and PA:A ratio over 60 months was performed. Independent effects of different variables on overall outcomes were evaluated using the Cox proportional hazards model.98 IPF patients with available HRCT scans had a mean pulmonary artery diameter and PA:A ratio of 32.8 mm and 0.94, respectively. Patients with a PA:A ratio >1 had higher risk of death or transplant compared with a PA:A ratio <=1 (p<0.001). A PA:A ratio >1 was also an independent predictor of outcomes in unadjusted and adjusted outcomes analyses (hazard ratio 3.99, p<0.001 and hazard ratio 3.35, p=0.002, respectively).A PA:A ratio >1 is associated with worse outcomes in patients with IPF. HRCT PA: A ratio measurement may assist in risk stratification and prognostication of IPF patients. PMID- 26846837 TI - Natural history of sleep disordered breathing in prepubertal children transitioning to adolescence. AB - Because there is a lack of agreed upon diagnostic criteria, it is critical to understand the natural history of obstructive sleep apnoea (OSA) in children in order to establish treatment strategies based on objective data.The Penn State Child Cohort is a representative, general-population sample of 700 elementary school children at baseline, of whom 421 were reassessed 8 years later, during adolescence.The remission of childhood apnoea-hypopnoea index (AHI) >=2 events per h in adolescence was 52.9%. Using the higher threshold of AHI >=5 events per h, remission was 100.0%, with 50.0% partially remitting to AHI 2- <5 events per h and the other half remitting to AHI <2 events per h. The incidence of adolescent AHI >=2 events per h in those with childhood AHI <2 events per h was 36.5%, while the incidence of AHI >=5 events per h in those with childhood AHI <5 events per h was 10.6%. This longitudinal study confirms that prepubertal OSA tends to resolve naturally during the transition to adolescence, and that primary snoring and mild sleep disordered breathing (SDB) do not appear to be strongly associated with progression to more severe SDB.The key risk factors for SDB in adolescence are similar to those found in middle-aged adults (i.e. male sex, older age and obesity). Moreover, consistent with recent studies in adults, this study includes the novel cross-sectional finding that visceral fat is associated with SDB as early as adolescence. PMID- 26846838 TI - Polymers of Z alpha1-antitrypsin are secreted in cell models of disease. PMID- 26846839 TI - Monoallelic germline ATM mutation and organising pneumonia induced by radiation therapy to the breast. PMID- 26846840 TI - Predictors of objective cough frequency in pulmonary sarcoidosis. AB - Cough is a common symptom of pulmonary sarcoidosis. This study aimed to quantify cough frequency, and investigate its relationship with cough reflex sensitivity, pulmonary function and health status.32 patients with pulmonary sarcoidosis were compared with 40 healthy controls. Cough reflex sensitivity to capsaicin, objective 24-h cough counts, cough-specific health status, cough severity and cough triggers were measured. The predictors of cough frequency in sarcoidosis were determined in a multivariate analysis.Objective cough frequency was significantly raised in patients with sarcoidosis compared with healthy controls (p<0.001) and patients with cough had an impaired health status. Patients with pulmonary sarcoidosis had a heightened cough reflex sensitivity compared with healthy controls (p<0.001). Only cough reflex sensitivity was significantly associated with objective cough frequency in multivariate analysis, explaining 42% of the variance (p<0.001). There was no association between cough frequency, lung function, number of organs involved, chest radiograph stage or serum angiotensin-converting enzyme levels.Cough is a common and significant symptom in patients with sarcoidosis. Ambulatory objective cough monitoring provides novel insights into the determinants of cough in sarcoidosis, suggesting that cough reflex sensitivity may be more important than lung function and other measures of disease severity, and this should be investigated further. PMID- 26846841 TI - GenAp: a distributed SQL interface for genomic data. AB - BACKGROUND: The impressively low cost and improved quality of genome sequencing provides to researchers of genetic diseases, such as cancer, a powerful tool to better understand the underlying genetic mechanisms of those diseases and treat them with effective targeted therapies. Thus, a number of projects today sequence the DNA of large patient populations each of which produces at least hundreds of terra-bytes of data. Now the challenge is to provide the produced data on demand to interested parties. RESULTS: In this paper, we show that the response to this challenge is a modified version of Spark SQL, a distributed SQL execution engine, that handles efficiently joins that use genomic intervals as keys. With this modification, Spark SQL serves such joins more than 50* faster than its existing brute force approach and 8* faster than similar distributed implementations. Thus, Spark SQL can replace existing practices to retrieve genomic data and, as we show, allow users to reduce the number of lines of software code that needs to be developed to query such data by an order of magnitude. PMID- 26846843 TI - Assessment of a computed tomography guided injection technique of the lumbo sacral disc in sheep. AB - OBJECTIVES: Recent data indicate that degeneration of intervertebral discs occurs naturally in sheep, with a higher prevalence at the level of the lumbo-sacral disc. The objective of this ex vivo study was to evaluate a computed tomography (CT) guided method of injection into the ovine lumbo-sacral disc. METHODS: Six euthanatized sheep were used for identification of the approach plane, the optimal direction of the needle and the mean distance from skin to disc. Dissection after injection of coloured ink was used to determine the anatomical structures that were penetrated. In seven other animals, all spines were assessed beforehand by CT and magnetic resonance imaging to determine whether disc pathology was present. The final position of the needle was assessed by CT to determine the accuracy of the technique. Contrast agent was injected to identify any problems associated with administration of liquid into the disc. RESULTS: The CT guided injection technique was easy to perform and enabled adequate positioning of the needle into all (n = 7) lumbo-sacral discs. Distance between the skin and the disc ranged between 12 and 17 cm. No organ, vascular or nervous structure was penetrated and the needle path remained intramuscular without penetration of the peritoneal cavity. Contrast medium leaked out through three degenerate discs. CLINICAL SIGNIFICANCE: The current study described a consistently safe and accurate CT guided injection technique to the lumbo-sacral disc for future in vivo experimental studies that will use sheep as animal model for human intervertebral disc disease disease. PMID- 26846842 TI - BKM-120 (Buparlisib): A Phosphatidyl-Inositol-3 Kinase Inhibitor with Anti Invasive Properties in Glioblastoma. AB - Glioblastoma is an aggressive, invasive tumor of the central nervous system (CNS). There is a widely acknowledged need for anti-invasive therapeutics to limit glioblastoma invasion. BKM-120 is a CNS-penetrant pan-class I phosphatidyl inositol-3 kinase (PI3K) inhibitor in clinical trials for solid tumors, including glioblastoma. We observed that BKM-120 has potent anti-invasive effects in glioblastoma cell lines and patient-derived glioma cells in vitro. These anti migratory effects were clearly distinguishable from cytostatic and cytotoxic effects at higher drug concentrations and longer durations of drug exposure. The effects were reversible and accompanied by changes in cell morphology and pronounced reduction in both cell/cell and cell/substrate adhesion. In vivo studies showed that a short period of treatment with BKM-120 slowed tumor spread in an intracranial xenografts. GDC-0941, a similar potent and selective PI3K inhibitor, only caused a moderate reduction in glioblastoma cell migration. The effects of BKM-120 and GDC-0941 were indistinguishable by in vitro kinase selectivity screening and phospho-protein arrays. BKM-120 reduced the numbers of focal adhesions and the velocity of microtubule treadmilling compared with GDC 0941, suggesting that mechanisms in addition to PI3K inhibition contribute to the anti-invasive effects of BKM-120. Our data suggest the CNS-penetrant PI3K inhibitor BKM-120 may have anti-invasive properties in glioblastoma. PMID- 26846844 TI - Scarcity of Primary Care Positions May Divert Physician Assistants Into Specialty Practice. AB - BACKGROUND: Physician assistants (PAs) are often suggested as a partial solution to predicted primary care workforce shortages, but a declining proportion of PAs are entering primary care practice. Policy efforts have focused on increasing primary care PA supply, but low labor market demand might be constricting the primary care PA pipeline. METHOD: In this descriptive, cross-sectional study, we compare primary care and specialty job postings to each other and to occupied PA positions. Job posting data for 2014 are from a leading labor analytics firm. RESULTS: Only 18% of job postings were in primary care, compared with 27% of occupied PA positions. The proportion of postings that were for primary care varied widely by state (9% to 40%) and were highest in the West. DISCUSSION: Job availability is a potential barrier to PAs practicing in primary care, especially in some locations. Other job factors are examined and policy solutions are suggested. PMID- 26846845 TI - Placenta growth factor and neuropilin-1 collaborate in promoting melanoma aggressiveness. AB - The placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family, which shares with VEGF-A the tyrosine kinase receptor VEGFR 1 and the co-receptor neuropilin-1 (NRP-1). In melanoma models, PlGF enhances tumour growth and neovessel formation, whereas NRP-1 promotes the metastatic process. Increased secretion of PlGF and expression of NRP-1 have also been involved in intrinsic or acquired resistance to anti-angiogenic therapies. In this study we investigated whether PlGF and NRP-1 cooperate in promoting melanoma aggressiveness independently of VEGFR-1. For this purpose, the melanoma cell clones M14-N, expressing NRP-1 and lacking VEGFR-1, and M14-C, devoid of both receptors, were used. M14-N cells are characterized by an invasive phenotype and vasculogenic mimicry, whereas M14-C cells possess a negligible invasive capacity. The results indicated that M14-N cells secrete higher levels of PlGF than M14-C cells and that PlGF is involved in the invasion of the extracellular matrix (ECM) and vasculogenic mimicry of M14-N cells. In fact, neutralizing antibodies against PlGF reverted ECM invasion in response to PlGF and markedly reduced the formation of tubule-like structures. Moreover, M14-N cells migrated in response to PlGF and chemotaxis was specifically abrogated by anti-NRP-1 antibodies, demonstrating that PlGF directly activates NRP-1 in the absence of VEGFR-1. We also compared the levels of PlGF in the plasma of patients affected by metastatic melanoma with those of healthy donors and evaluated whether PlGF levels could be affected by a bevacizumab-containing chemotherapy regimen. Melanoma patients showed a 20-fold increase in plasma PlGF and the bevacizumab-containing regimen induced a reduction of VEGF-A and in a further increase of PlGF. In conclusion, our studies suggest that the activation of NRP-1 by PlGF directly contributes to melanoma aggressiveness and represents a potential compensatory pro-angiogenic mechanism that may contribute to the resistance to therapies targeting VEGF-A. PMID- 26846846 TI - The Structure-property Relationships of D-pi-A BODIPY Dyes for Dye-sensitized Solar Cells. AB - BODIPY dyes have attracted considerable attention as potential photosensitizers in dye-sensitized solar cells (DSSCs) owing to their excellent optical properties and facile structural modification. This account focuses on recent advances in the molecular design of D-pi-A BODIPY dyes for applications in DSSCs. Special attention has been paid to the structure-property relationships of D-pi-A BODIPY dyes for DSSCs. The developmental process in the modified position at the BODIPY core with a donor/acceptor is described. The devices based on 2,6-modified BODIPY dyes exhibit better photovoltaic performance over other modified BODIPY dyes. Meanwhile, the research reveals the correlation of molecular structures (various donor chromophores, extended units, molecular frameworks, and long alkyl groups) with their photophysical and electrochemical properties and relates it to their performance in DSSCs. The structure-property relationships give valuable information and guidelines for designing new D-pi-A BODIPY dyes for DSSCs. PMID- 26846847 TI - Highly exposed surface area of {001} facets dominated BiOBr nanosheets with enhanced visible light photocatalytic activity. AB - Two groups of BiOBr nanosheets with different sizes and similar exposure percentages of {001} facets were selectively synthesized by simple hydrothermal methods. The obtained samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and UV-vis diffuse reflectance spectroscopy (DRS). The photocatalytic activity was estimated from the degradation of organic pollutants under visible-light irradiation. The results indicated that BiOBr nanosheets with similar exposure percentages of {001} facets but smaller sizes exhibited higher photocatalytic activity. Furthermore, the effects of the size, including the thickness and length, of BiOBr nanosheets were also studied. The results showed that the impact of thickness was more significant than that of length. It was found that reducing the thickness of BiOBr nanosheets can significantly increase the exposed surface areas of {001} facets (S{001}), but not necessarily the exposure percentage of {001} facets. Moreover, in our experiment, the photocatalytic activity of BiOBr nanosheets increased linearly with an increase in S{001} in the range of 0.022 to 0.111 nm(-1). Therefore, the photocatalytic activity of BiOBr nanosheets depended on the exposed surface areas of {001} facets rather than the exposure percentage of {001} facets. The enhancement of the photocatalytic activity of ultrathin BiOBr nanosheets with large exposed surface areas of {001} facets can be mainly ascribed to their enhanced absorption of visible light and improved separation efficiency of charge carriers. PMID- 26846848 TI - PPARalpha (Peroxisome Proliferator-activated Receptor alpha) Activation Reduces Hepatic CEACAM1 Protein Expression to Regulate Fatty Acid Oxidation during Fasting-refeeding Transition. AB - Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed at high levels in the hepatocyte, consistent with its role in promoting insulin clearance in liver. CEACAM1 also mediates a negative acute effect of insulin on fatty acid synthase activity. Western blot analysis reveals lower hepatic CEACAM1 expression during fasting. Treating of rat hepatoma FAO cells with Wy14,643, an agonist of peroxisome proliferator-activated receptor alpha (PPARalpha), rapidly reduces Ceacam1 mRNA and CEACAM1 protein levels within 1 and 2 h, respectively. Luciferase reporter assay shows a decrease in the promoter activity of both rat and mouse genes by Pparalpha activation, and 5'-deletion and block substitution analyses reveal that the Pparalpha response element between nucleotides -557 and 543 is required for regulation of the mouse promoter activity. Chromatin immunoprecipitation analysis demonstrates binding of liganded Pparalpha toCeacam1promoter in liver lysates ofPparalpha(+/+), but notPparalpha(-/-)mice fed a Wy14,643-supplemented chow diet. Consequently, Wy14,643 feeding reduces hepatic Ceacam1 mRNA and CEACAM1 protein levels, thus decreasing insulin clearance to compensate for compromised insulin secretion and maintain glucose homeostasis and insulin sensitivity in wild-type mice. Together, the data show that the low hepatic CEACAM1 expression at fasting is mediated by Pparalpha dependent mechanisms. Changes in CEACAM1 expression contribute to the coordination of fatty acid oxidation and insulin action in the fasting-refeeding transition. PMID- 26846849 TI - Serine 302 Phosphorylation of Mouse Insulin Receptor Substrate 1 (IRS1) Is Dispensable for Normal Insulin Signaling and Feedback Regulation by Hepatic S6 Kinase. AB - Constitutive activation of the mammalian target of rapamycin complex 1 and S6 kinase (mTORC1-> S6K) attenuates insulin-stimulated Akt activity in certain tumors in part through "feedback" phosphorylation of the upstream insulin receptor substrate 1 (IRS1). However, the significance of this mechanism for regulating insulin sensitivity in normal tissue remains unclear. We investigated the function of Ser-302 in mouse IRS1, the major site of its phosphorylation by S6K in vitro, through genetic knock-in of a serine-to-alanine mutation (A302). Although insulin rapidly stimulated feedback phosphorylation of Ser-302 in mouse liver and muscle, homozygous A302 mice (A/A) and their knock-in controls (S/S) exhibited similar glucose homeostasis and muscle insulin signaling. Furthermore, both A302 and control primary hepatocytes from which Irs2 was deleted showed marked inhibition of insulin-stimulated IRS1 tyrosine phosphorylation and PI3K binding after emetine treatment to raise intracellular amino acids and activate mTORC1 -> S6K signaling. To specifically activate mTORC1 in mouse tissue, we deleted hepatic Tsc1 using Cre adenovirus. Although it moderately decreased IRS1/PI3K association and Akt phosphorylation in liver, Tsc1 deletion failed to cause glucose intolerance or promote hyperinsulinemia in mixed background A/A or S/S mice. Moreover, Tsc1 deletion failed to stimulate phospho-Ser-302 or other putative S6K sites within IRS1, whereas ribosomal S6 protein was constitutively phosphorylated. Following acute Tsc1 deletion from hepatocytes, Akt phosphorylation, but not IRS1/PI3K association, was rapidly restored by treatment with the mTORC1 inhibitor rapamycin. Thus, within the hepatic compartment, mTORC1 -> S6K signaling regulates Akt largely through IRS-independent means with little effect upon physiologic insulin sensitivity. PMID- 26846850 TI - Non-equivalent Roles of AGO1 and AGO2 in mRNA Turnover and Translation of Cyclin D1 mRNA. AB - Mammalian Argonaute proteins (AGO1-4), in combination with microRNAs (miRs), bind to target mRNAs to initiate degradation and/or translation repression, but the relationships between these two effects is unclear. Although the AGO isoforms ofDrosophilaand plants perform different functions, mammalian AGO isoforms are considered to be functionally degenerate in terms of miR loading and downstream silencing effects. However, we found that, in quiescent (G0) rat myoblasts transiting to the G1 phase, cyclin D1 (Ccnd1) mRNA was associated with two functionally distinct AGO-miR complexes. While AGO1-miR-1 down-regulated the mRNA level, AGO2-let-7 delayed the timing of translation. Knockdown (KD) of AGO2, or antisense-mediated depletion of Let-7, caused Ccnd1 translation to occur earlier, but had no significant effect on mRNA abundance. Conversely, down-regulation of either AGO1 or miR-1, resulted in elevated Ccnd1 mRNA levels at early times, but failed to affect the timing of translation. These results show that the two miR mediated silencing effects, viz. mRNA decay and translation repression, are independent processes induced by individual AGO isoforms in association with specific miRs. PMID- 26846851 TI - Phenotype-based Discovery of 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol as a Novel Regulator of Ocular Angiogenesis. AB - Retinal angiogenesis is tightly regulated to meet oxygenation and nutritional requirements. In diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, uncontrolled angiogenesis can lead to blindness. Our goal is to better understand the molecular processes controlling retinal angiogenesis and discover novel drugs that inhibit retinal neovascularization. Phenotype-based chemical screens were performed using the ChemBridge Diverset(TM)library and inhibition of hyaloid vessel angiogenesis in Tg(fli1:EGFP) zebrafish. 2-[(E)-2-(Quinolin-2-yl)vinyl]phenol, (quininib) robustly inhibits developmental angiogenesis at 4-10 MUmin zebrafish and significantly inhibits angiogenic tubule formation in HMEC-1 cells, angiogenic sprouting in aortic ring explants, and retinal revascularization in oxygen induced retinopathy mice. Quininib is well tolerated in zebrafish, human cell lines, and murine eyes. Profiling screens of 153 angiogenic and inflammatory targets revealed that quininib does not directly target VEGF receptors but antagonizes cysteinyl leukotriene receptors 1 and 2 (CysLT1-2) at micromolar IC50values. In summary, quininib is a novel anti-angiogenic small-molecule CysLT receptor antagonist. Quininib inhibits angiogenesis in a range of cell and tissue systems, revealing novel physiological roles for CysLT signaling. Quininib has potential as a novel therapeutic agent to treat ocular neovascular pathologies and may complement current anti-VEGF biological agents. PMID- 26846852 TI - Cell Autonomous and Nonautonomous Function of CUL4B in Mouse Spermatogenesis. AB - CUL4B ubiquitin ligase belongs to the cullin-RING ubiquitin ligase family. Although sharing many sequence and structural similarities, CUL4B plays distinct roles in spermatogenesis from its homologous protein CUL4A. We previously reported that genetic ablation ofCul4ain mice led to male infertility because of aberrant meiotic progression. In the present study, we generated Cul4bgerm cell specific conditional knock-out (Cul4b(Vasa)),as well asCul4bglobal knock-out (Cul4b(Sox2)) mouse, to investigate its roles in spermatogenesis. Germ cell specific deletion of Cul4bled to male infertility, despite normal testicular morphology and comparable numbers of spermatozoa. Notably, significantly impaired sperm mobility caused by reduced mitochondrial activity and glycolysis level were observed in the majority of the mutant spermatozoa, manifested by low, if any, sperm ATP production. Furthermore,Cul4b(Vasa)spermatozoa exhibited defective arrangement of axonemal microtubules and flagella outer dense fibers. Our mass spectrometry analysis identified INSL6 as a novel CUL4B substrate in male germ cells, evidenced by its direct polyubiquination and degradation by CUL4B E3 ligase. Nevertheless,Cul4bglobal knock-out males lost their germ cells in an age dependent manner, implying failure of maintaining the spermatogonial stem cell niche in somatic cells. Taken together, our results show that CUL4B is indispensable to spermatogenesis, and it functions cell autonomously in male germ cells to ensure spermatozoa motility, whereas it functions non-cell-autonomously in somatic cells to maintain spermatogonial stemness. Thus, CUL4B links two distinct spermatogenetic processes to a single E3 ligase, highlighting the significance of ubiquitin modification during spermatogenesis. PMID- 26846853 TI - beta-Arrestins Negatively Regulate the Toll Pathway in Shrimp by Preventing Dorsal Translocation and Inhibiting Dorsal Transcriptional Activity. AB - The Toll signaling pathway plays an important role in the innate immunity ofDrosophila melanogasterand mammals. The activation and termination of Toll signaling are finely regulated in these animals. Although the primary components of the Toll pathway were identified in shrimp, the functions and regulation of the pathway are seldom studied. We first demonstrated that the Toll signaling pathway plays a central role in host defense againstStaphylococcus aureusby regulating expression of antimicrobial peptides in shrimp. We then found that beta-arrestins negatively regulate Toll signaling in two different ways. beta Arrestins interact with the C-terminal PEST domain of Cactus through the arrestin N domain, and Cactus interacts with the RHD domain of Dorsal via the ankyrin repeats domain, forming a heterotrimeric complex of beta-arrestin.Cactus.Dorsal, with Cactus as the bridge. This complex prevents Cactus phosphorylation and degradation, as well as Dorsal translocation into the nucleus, thus inhibiting activation of the Toll signaling pathway. beta-Arrestins also interact with non phosphorylated ERK (extracellular signal-regulated protein kinase) through the arrestin-C domain to inhibit ERK phosphorylation, which affects Dorsal translocation into the nucleus and phosphorylation of Dorsal at Ser(276)that impairs Dorsal transcriptional activity. Our study suggests that beta-arrestins negatively regulate the Toll signaling pathway by preventing Dorsal translocation and inhibiting Dorsal phosphorylation and transcriptional activity. PMID- 26846854 TI - Preparation and Characterization of Stable alpha-Synuclein Lipoprotein Particles. AB - Multiple neurodegenerative diseases are caused by the aggregation of the human alpha-Synuclein (alpha-Syn) protein. alpha-Syn possesses high structural plasticity and the capability of interacting with membranes. Both features are not only essential for its physiological function but also play a role in the aggregation process. Recently it has been proposed that alpha-Syn is able to form lipid-protein particles reminiscent of high-density lipoproteins. Here, we present a method to obtain a stable and homogeneous population of nanometer-sized particles composed of alpha-Syn and anionic phospholipids. These particles are called alpha-Syn lipoprotein (nano)particles to indicate their relationship to high-density lipoproteins formed by human apolipoproteins in vivo and of in vitro self-assembling phospholipid bilayer nanodiscs. Structural investigations of the alpha-Syn lipoprotein particles by circular dichroism (CD) and magic angle solid state nuclear magnetic resonance (MAS SS-NMR) spectroscopy establish that alpha Syn adopts a helical secondary structure within these particles. Based on cryo electron microscopy (cryo-EM) and dynamic light scattering (DLS) alpha-Syn lipoprotein particles have a defined size with a diameter of ~23 nm. Chemical cross-linking in combination with solution-state NMR and multiangle static light scattering (MALS) of alpha-Syn particles reveal a high-order protein-lipid entity composed of ~8-10 alpha-Syn molecules. The close resemblance in size between cross-linked in vitro-derived alpha-Syn lipoprotein particles and a cross-linked species of endogenous alpha-Syn from SH-SY5Y human neuroblastoma cells indicates a potential functional relevance of alpha-Syn lipoprotein nanoparticles. PMID- 26846855 TI - Oxygen-dependent Regulation of Erythropoietin Receptor Turnover and Signaling. AB - von Hippel-Lindau (VHL) disease is a rare familial cancer predisposition syndrome caused by a loss or mutation in a single gene,VHL, but it exhibits a wide phenotypic variability that can be categorized into distinct subtypes. The phenotypic variability has been largely argued to be attributable to the extent of deregulation of the alpha subunit of hypoxia-inducible factor alpha, a well established target of VHL E3 ubiquitin ligase, ECV (Elongins/Cul2/VHL). Here, we show that erythropoietin receptor (EPOR) is hydroxylated on proline 419 and 426 via prolyl hydroxylase 3. EPOR hydroxylation is required for binding to the beta domain of VHL and polyubiquitylation via ECV, leading to increased EPOR turnover. In addition, several type-specific VHL disease-causing mutants, including those that have retained proper binding and regulation of hypoxia-inducible factor alpha, showed a severe defect in binding prolyl hydroxylated EPOR peptides. These results identify EPOR as the secondbona fidehydroxylation-dependent substrate of VHL that potentially influences oxygen homeostasis and contributes to the complex genotype-phenotype correlation in VHL disease. PMID- 26846856 TI - Novel Roles of the Non-catalytic Elements of Yeast Protein-disulfide Isomerase in Its Interplay with Endoplasmic Reticulum Oxidoreductin 1. AB - The formation of disulfide bonds in the endoplasmic reticulum (ER) of eukaryotic cells is catalyzed by the sulfhydryl oxidase, ER oxidoreductin 1 (Ero1), and protein-disulfide isomerase (PDI). PDI is oxidized by Ero1 to continuously introduce disulfides into substrates, and feedback regulates Ero1 activity by manipulating the regulatory disulfides of Ero1. In this study we find that yeast Ero1p is enzymatically active even with its regulatory disulfides intact, and further activation of Ero1p by reduction of the regulatory disulfides requires the reduction of non-catalytic Cys(90)-Cys(97)disulfide in Pdi1p. The principal client-binding site in the Pdi1pb' domain is necessary not only for the functional Ero1p-Pdi1p disulfide relay but also for the activation of Ero1p. We also demonstrate by complementary activation assays that the regulatory disulfides in Ero1p are much more stable than those in human Ero1alpha. These new findings on yeast Ero1p-Pdi1p interplay reveal significant differences from our previously identified mode of human Ero1alpha-PDI interplay and provide insights into the evolution of the eukaryotic oxidative protein folding pathway. PMID- 26846858 TI - Missed Ischemic Stroke Diagnosis in the Emergency Department by Emergency Medicine and Neurology Services. AB - BACKGROUND AND PURPOSE: The failure to recognize an ischemic stroke in the emergency department is a missed opportunity for acute interventions and for prompt treatment with secondary prevention therapy. Our study examined the diagnosis of acute ischemic stroke in the emergency department of an academic teaching hospital and a large community hospital. METHODS: A retrospective chart review was performed from February 2013 to February 2014. RESULTS: A total of 465 patients with ischemic stroke were included in the analysis; 280 patients from the academic hospital and 185 patients from the community hospital. One hundred three strokes were initially misdiagnosed that is 22% of the included strokes at the combined centers. Fifty-five of these were missed at the academic hospital (22%) [corrected] and 48 were at the community hospital (26%, P=0.11). Thirty three percent of missed cases presented within a 3-hour time window for recombinant tissue-type plasminogen activator eligibility. An additional 11% presented between 3 and 6 hours of symptom onset for endovascular consideration. Symptoms independently associated with greater odds of a missed stroke diagnosis were nausea/vomiting (odds ratio, 4.02; 95% confidence interval, 1.60-10.1), dizziness (odds ratio, 1.99; 95% confidence interval, 1.03-3.84), and a positive stroke history (odds ratio, 2.40; 95% confidence interval, 1.30-4.42). Thirty seven percent of posterior strokes were initially misdiagnosed compared with 16% of anterior strokes (P<0.001). CONCLUSIONS: Atypical symptoms associated with posterior circulation strokes lead to misdiagnoses. This was true at both an academic center and a large community hospital. Future studies need to focus on the evaluation of identification systems and tools in the emergency department to improve the accuracy of stroke diagnosis. PMID- 26846857 TI - Predicting Intracerebral Hemorrhage Growth With the Spot Sign: The Effect of Onset-to-Scan Time. AB - BACKGROUND AND PURPOSE: Hematoma expansion after acute intracerebral hemorrhage is common and is associated with early deterioration and poor clinical outcome. The computed tomographic angiography (CTA) spot sign is a promising predictor of expansion; however, frequency and predictive values are variable across studies, possibly because of differences in onset-to-CTA time. We performed a patient level meta-analysis to define the relationship between onset-to-CTA time and frequency and predictive ability of the spot sign. METHODS: We completed a systematic review for studies of CTA spot sign and hematoma expansion. We subsequently pooled patient-level data on the frequency and predictive values for significant hematoma expansion according to 5 predefined categorized onset-to-CTA times. We calculated spot-sign frequency both as raw and frequency-adjusted rates. RESULTS: Among 2051 studies identified, 12 met our inclusion criteria. Baseline hematoma volume, spot-sign status, and time-to-CTA were available for 1176 patients, and 1039 patients had follow-up computed tomographies for hematoma expansion analysis. The overall spot sign frequency was 26%, decreasing from 39% within 2 hours of onset to 13% beyond 8 hours (P<0.001). There was a significant decrease in hematoma expansion in spot-positive patients as onset-to-CTA time increased (P=0.004), with positive predictive values decreasing from 53% to 33%. CONCLUSIONS: The frequency of the CTA spot sign is inversely related to intracerebral hemorrhage onset-to-CTA time. Furthermore, the positive predictive value of the spot sign for significant hematoma expansion decreases as time-to CTA increases. Our results offer more precise risk stratification for patients with acute intracerebral hemorrhage and will help refine clinical prediction rules for intracerebral hemorrhage expansion. PMID- 26846860 TI - Significance of Cerebral Small-Vessel Disease in Acute Intracerebral Hemorrhage. AB - BACKGROUND AND PURPOSE: The significance of structural changes associated with cerebral small-vessel disease (SVD), including white matter lesions (WML), lacunes, and brain atrophy, to outcome from acute intracerebral hemorrhage is uncertain. We determined associations of computed tomographic radiological manifestations of cerebral SVD and outcomes, and in terms of any differential effect of early intensive blood pressure-lowering treatment, in the large-scale Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT2). METHODS: We graded WML (van Swieten scale), the presence of lacunes, and brain atrophy (2 linear measurements and visual rating) for 2069 of 2839 patients with available baseline brain computed tomography (<6 hours of intracerebral hemorrhage onset) by 3 independent neurologists blind to clinical data. RESULTS: WML grade and 2 linear measurements of brain atrophy were associated with death or major disability at 90 days: multivariable-adjusted odds ratios for WML (grade 3 and 4 versus 0), frontal ratio, and third ventricle Sylvian fissure distance (most versus least severe atrophy quartile) were 1.42 (95% confidence interval, 1.02-1.98), 1.47 (1.08-1.99), and 1.64 (1.21-2.22), respectively (all P for trend <0.05). There was no association between lacunes and outcomes. There were no significant differences in the effects of intensive blood pressure-lowering across subgroups of cerebral SVD. CONCLUSIONS: Preexisting cerebral SVD manifestations of WML and brain atrophy predict poor outcome in acute intracerebral hemorrhage. There is no apparent hazard of early intensive lowering of blood pressure according to the INTERACT2 protocol, in patients with underlying cerebral SVD. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00716079. PMID- 26846859 TI - Thrombus Permeability Is Associated With Improved Functional Outcome and Recanalization in Patients With Ischemic Stroke. AB - BACKGROUND AND PURPOSE: Preclinical studies showed that thrombi can be permeable and may, therefore, allow for residual blood flow in occluded arteries of patients having acute ischemic stroke. This perviousness may increase tissue oxygenation, improve thrombus dissolution, and augment intra-arterial treatment success. We hypothesize that the combination of computed tomographic angiography and noncontrast computed tomography imaging allows measurement of contrast agent penetrating a permeable thrombus, and it is associated with improved outcome. METHODS: Thrombus and contralateral artery attenuations in noncontrast computed tomography and computed tomographic angiography images were measured in 184 Multicenter Randomized Clinical trial of Endovascular treatment of acute ischemic stroke in the Netherlands (MR CLEAN) patients with thin-slice images. Two quantitative estimators of the thrombus permeability were introduced: computed tomographic angiography attenuation increase (Delta) and thrombus void fraction (epsilon). Patients were dichotomized as having a pervious or impervious thrombus and associated with outcome, recanalization, and final infarct volume. RESULTS: Patients with Delta>=10.9 HU (n=81 [44%]) and epsilon>=6.5% (n=77 [42%]) were classified as having a pervious thrombus. These patients were 3.2 (95% confidence interval, 1.7-6.4) times more likely to have a favorable outcome, and 2.5 (95% confidence interval, 1.3-4.8) times more likely to recanalyze, for Delta based classification, and similarly for epsilon. These odds ratios were independent from intravenous or intra-arterial treatment. Final infarct volume was negatively correlated with both perviousness estimates (correlation coefficient, -0.39 for Delta and -0.40 for epsilon). CONCLUSIONS: This study shows that simultaneous measurement of thrombus attenuation in noncontrast computed tomography and computed tomographic angiography allows for quantification of thrombus perviousness. Thrombus perviousness is strongly associated with improved functional outcome, smaller final infarct volume, and higher recanalization rate. PMID- 26846862 TI - Imaging and Baseline Predictors of Cognitive Performance in Minor Ischemic Stroke and Patients With Transient Ischemic Attack at 90 Days. AB - BACKGROUND AND PURPOSE: Few studies have examined predictors of cognitive impairment after minor ischemic stroke and transient ischemic attack (TIA). We examined clinical and imaging features associated with worse cognitive performance at 90 days. METHODS: TIA or patients with minor stroke underwent neuropsychological testing 90 days post event. Z scores were calculated for cognitive tests, and then grouped into domains of executive function (EF), psychomotor processing speed (PS), and memory. White matter hyperintensity and diffusion-weighted imaging volumes were measured on baseline magnetic resonance imaging. Ninety-day outcomes included modified Rankin Scale (mRS) and Centre for Epidemiological Studies Depression Scale (CES-D) score. RESULTS: Ninety-two patients were included, 76% male, 54% TIA, and mean age 65.1+/-12.0. Sixty-four percent were diffusion-weighted imaging positive. Median domain z scores were not significantly different from published norms (P>0.05): memory -0.03, EF -0.12, and PS -0.05. Patient performance >=1 SD below normal was 20% on memory, 16% on PS, and 17% on EF. Cognitive scores did not differ by diagnosis (stroke versus TIA), stroke pathogenesis, presence of obstructive sleep apnea, and diffusion weighted imaging or white matter hyperintensity volumes. In multivariable analyses, lower EF was associated with previous cortical infarct on magnetic resonance imaging (P=0.03), mRS score of >1; P=0.0003 and depressive symptoms (CES-D >=16; P=0.03). Lower PS scores were associated with previous cortical infarct (P=0.02), acute bilateral positive diffusion-weighted imaging (P=0.02), mRS score of >1 (P=0.003), and CES-D >=16 (P=0.03). CONCLUSIONS: Despite average range cognitive performance in this TIA and population with minor stroke, we found associations of EF and PS with evidence of previous stroke, postevent disability, and depression. PMID- 26846861 TI - Nonpsychotic Mental Disorders in Teenage Males and Risk of Early Stroke: A Population-Based Study. AB - BACKGROUND AND PURPOSE: Although the incidence of stroke is on the decline worldwide, this is not the case for early stroke. We aimed to determine whether nonpsychotic mental disorder at the age of 18 years is a risk factor for early stroke, and if adolescent cardiovascular fitness and intelligence quotient might attenuate the risk. METHOD: Population-based Swedish cohort study of conscripts (n=1 163 845) who enlisted during 1968 to 2005. At conscription, 45 064 males were diagnosed with nonpsychotic mental disorder. Risk of stroke during follow-up (5-42 years) was calculated with Cox proportional hazards models. Objective baseline measures of fitness and cognition were included in the models in a second set of analyses. RESULTS: There were 7770 first-time stroke events. In adjusted models, increased risk for stroke was observed in men diagnosed with depressive/neurotic disorders (hazard ratio [HR], 1.23; 95% confidence interval [CI], 1.11-1.37), personality disorders (HR, 1.52; 95% CI, 1.29-1.78), and alcohol/substance use disorders (HR, 1.61; 95% CI, 1.41-1.83) at conscription. Corresponding figures for fatal stroke were HR, 1.38; 95% CI, 1.06 to 1.79; HR, 2.26; 95% CI, 1.60 to 3.19; and HR, 2.20; 95% CI, 1.63 to 2.96. HRs for stroke were attenuated when fitness level and intelligence quotient were introduced. Associations remained significant for personality disorders and alcohol/substance use in the fully adjusted models. The interaction term was statistically significant for fitness but not for intelligence quotient. CONCLUSIONS: Our findings suggest that fitness may modify associations between nonpsychotic disorders and stroke. It remains to be clarified whether interventions designed to improve fitness in mentally ill youth can influence future risk of early stroke. PMID- 26846864 TI - Temporal Course of Dynamic Cerebral Autoregulation in Patients With Intracerebral Hemorrhage. AB - BACKGROUND AND PURPOSE: Cerebral autoregulation is crucial in patients with intracerebral hemorrhage. Dynamic cerebral autoregulation is probably altered in acute intracerebral hemorrhage; however, the temporal course of dynamic cerebral autoregulation and its correlation with clinical factors and outcomes are poorly understood. METHODS: Forty-three acute supratentorial intracerebral hemorrhage patients (53.7+/-10.0 years old, 30 men) were enrolled for serial measurements performed on days 1 to 2, 4 to 6, 10 to 12, and 30 days after ictus. Noninvasive continuous cerebral blood flow velocity and arterial blood pressure were recorded simultaneously using transcranial Doppler and a servo-controlled plethysmograph, respectively. Transfer function analysis was used to derive the autoregulatory parameters, including phase difference (PD), gain, and the rate of recovery of cerebral blood flow velocity. Results were compared with healthy controls and correlated with clinical factors and the 90-day outcome. RESULTS: PD did not differ between affected and unaffected hemispheres over time. A significant lower PD (indicating dynamic cerebral autoregulation impaired) was found in bilateral hemispheres on days 1 to 2, 4 to 6, and 10 to 12, followed by later recovery on day 30. Lower bilateral PD on days 1 to 2 was associated with poorer Glasgow Coma Scale score at that time. Lower affected-side PD on days 4 to 6 was an independent predictive value for a poorer modified Rankin Scale at 90 days. CONCLUSIONS: In patients with supratentorial intracerebral hemorrhage, dynamic cerebral autoregulation is bilaterally impaired lasting at least 10 to 12 days and recovers within a month. Individual PD value is associated with clinical status at acute stage and affected-side PD on days 4 to 6 can be an independent predictor for clinical outcome. PMID- 26846865 TI - Desmoteplase After Ischemic Stroke in Patients With Occlusion or High-Grade Stenosis in Major Cerebral Arteries. PMID- 26846866 TI - Peripheral Blood MCEMP1 Gene Expression as a Biomarker for Stroke Prognosis. AB - BACKGROUND AND PURPOSE: A limitation when making early decisions on stroke management is the lack of rapid diagnostic and prognostic testing. Our study sought to identify peripheral blood RNA biomarkers associated with stroke. The secondary aims were to assess the discriminative capacity of RNA biomarkers for primary stroke type and stroke prognosis at 1-month. METHODS: Whole-blood gene expression profiling was conducted on the discovery cohort: 129 first-time stroke cases that had blood sampling within 5 days of symptom onset and 170 control participants with no history of stroke. RESULTS: Through multiple regression analysis, we determined that expression of the gene MCEMP1 had the strongest association with stroke of 11 181 genes tested. MCEMP1 increased by 2.4-fold in stroke when compared with controls (95% confidence interval, 2.0-2.8; P=8.2*10( 22)). In addition, expression was elevated in intracerebral hemorrhage when compared with ischemic stroke cases (P=3.9*10(-4)). MCEMP1 was also highest soon after symptom onset and had no association with stroke risk factors. Furthermore, MCEMP1 expression independently improved discrimination of 1-month outcome. Indeed, discrimination models for disability and mortality that included MCEMP1 expression, baseline modified Rankin Scale score, and primary stroke type improved discrimination when compared with a model without MCEMP1 (disability Net Reclassification Index, 0.76; P=3.0*10(-6) and mortality Net Reclassification Index, 1.3; P=1.1*10(-9)). Significant associations with MCEMP1 were confirmed in an independent validation cohort of 28 stroke cases and 34 controls. CONCLUSIONS: This study demonstrates that peripheral blood expression of MCEMP1 may have utility for stroke diagnosis and as a prognostic biomarker of stroke outcome at 1 month. PMID- 26846867 TI - A divergent spirochete strain isolated from a resident of the southeastern United States was identified by multilocus sequence typing as Borrelia bissettii. AB - BACKGROUND: Out of 20 spirochete species from Borrelia burgdorferi sensu lato (s.l.) complex recognized to date some are considered to have a limited distribution, while others are worldwide dispersed. Among those are Borrelia burgdorferi sensu stricto (s.s.) and Borrelia bissettii which are distributed both in North America and in Europe. While B. burgdorferi s.s. is recognized as a cause of Lyme borreliosis worldwide, involvement of B. bissettii in human Lyme disease was not so definite yet. FINDINGS: Multilocus sequence typing of spirochete isolates originating from residents of Georgia and Florida, USA, revealed the presence of two Borrelia burgdorferi sensu stricto strains highly similar to those from endemic Lyme borreliosis regions of the northeastern United States, and an unusual strain that differed from any previously described in Europe or North America. Based on phylogenetic analysis of eight chromosomally located housekeeping genes divergent strain clustered between Borrelia bissettii and Borrelia carolinensis, two species from the B.burgdorferi s.l. complex, widely distributed among the multiple hosts and vector ticks in the southeastern United States. The genetic distance analysis showed a close relationship of the diverged strain to B. bissettii. CONCLUSIONS: Here, we present the analysis of the first North American human originated live spirochete strain that revealed close relatedness to B. bissettii. The potential of B. bissettii to cause human disease, even if it is infrequent, is of importance for clinicians due to the extensive range of its geographic distribution. PMID- 26846868 TI - Association between Serum IGF-I levels and Postoperative Delirium in Elderly Subjects Undergoing Elective Knee Arthroplasty. AB - Evidence is mixed for an association between serum insulin-like growth factor-I (IGF-I) levels and postoperative delirium (POD). The current study assessed preoperative serum IGF-I levels as a predictor of incident delirium in non demented elderly elective knee arthroplasty patients. Preoperative serum levels of total IGF-I were measured using a commercially available Human IGF-I ELISA kit. POD incidence and severity were determined using DSM-IV criteria and the Delirium Rating Scale-Revised-98 (DRS-R98), respectively. Median IGF-I levels in delirious (62.6 ng/ml) and non-delirious groups (65.9 ng/ml) were not significantly different (p = 0.141). The ratio (95% CI) of geometric means, D/ND, was 0.86 (0.70, 1.06). The Hodges-Lehmann median difference estimate was 7.23 ng/mL with 95% confidence interval (-2.32, 19.9). In multivariate logistic regression analysis IGF-I level was not a significant predictor of incident POD after correcting for medical comorbidities. IGF-I levels did not correlate with DRS-R98 scores for delirium severity. In conclusion, we report no evidence of association between serum IGF-I levels and incidence of POD, although the sample size was inadequate for a conclusive study. Further efforts to investigate IGF-I as a delirium risk factor in elderly should address comorbidities and confounders that influence IGF-I levels. PMID- 26846870 TI - Maternal and neonatal outcomes of antenatal anemia in a Scottish population: a retrospective cohort study. AB - INTRODUCTION: Antenatal anemia is a major public health problem in the UK, yet there is limited high quality evidence for associated poor clinical outcomes. The objectives of this study were to estimate the incidence and clinical outcomes of antenatal anemia in a Scottish population. MATERIAL AND METHODS: A retrospective cohort study of 80 422 singleton pregnancies was conducted using data from the Aberdeen Maternal and Neonatal Databank between 1995 and 2012. Antenatal anemia was defined as haemoglobin <= 10 g/dl during pregnancy. Incidence was calculated with 95% confidence intervals and compared over time using a chi-squared test for trend. Multivariable logistic regression was used to adjust for confounding variables. Results are presented as adjusted odds ratios with 95% confidence interval. RESULTS: The overall incidence of antenatal anemia was 9.3 cases/100 singleton pregnancies (95% confidence interval 9.1-9.5), decreasing from 16.9/100 to 4.1/100 singleton pregnancies between 1995 and 2012 (p < 0.001). Maternal anemia was associated with antepartum hemorrhage (adjusted odds ratio 1.26, 95% confidence interval 1.17-1.36), postpartum infection (adjusted odds ratio 1.89, 95% confidence interval 1.39-2.57), transfusion (adjusted odds ratio 1.87, 95% confidence interval 1.65-2.13) and stillbirth (adjusted odds ratio 1.42, 95% confidence interval 1.04-1.94), reduced odds of postpartum hemorrhage (adjusted odds ratio 0.92, 95% confidence interval 0.86-0.98) and low birthweight (adjusted odds ratio 0.77, 95% confidence interval 0.69-0.86). No other outcomes were statistically significant. CONCLUSIONS: This study shows the incidence of antenatal anemia is decreasing steadily within this Scottish population. However, given that anemia is a readily correctable risk factor for major causes of morbidity and mortality in the UK, further work is required to investigate appropriate preventive measures. PMID- 26846871 TI - The use of new anticoagulant drugs in ventricular assist devices: Another brick in the wall? PMID- 26846869 TI - Anogenital distance as a marker of androgen exposure in humans. AB - Abnormal foetal testis development has been proposed to underlie common disorders of the male reproductive system such as cryptorchidism, hypospadias, reduced semen quality and testicular germ cell tumour, which are regarded as components of a 'testicular dysgenesis syndrome'. The increasing trends and geographical variation in their incidence have been suggested to result from in utero exposure to environmental chemicals acting as endocrine disruptors. In rodents, the anogenital distance (AGD), measured from the anus to the base of genital tubercle, is a sensitive biomarker of androgen exposure during a critical embryonic window of testis development. In humans, several epidemiological studies have shown alterations in AGD associated with prenatal exposure to several chemicals with potential endocrine disrupting activity. However, the link between AGD and androgen exposure in humans is not well-defined. This review focuses on the current evidence for such a relationship. As in rodents, a clear gender difference is detected during foetal development of the AGD in humans which is maintained thereafter. Reduced AGD in association with clinically relevant outcomes of potential environmental exposures, such as cryptorchidism or hypospadias, is in keeping with AGD as a marker of foetal testicular function. Furthermore, AGD may reflect variations in prenatal androgen exposure in healthy children as shorter AGD at birth is associated with reduced masculine play behaviour in preschool boys. Several studies provide evidence linking shorter AGD with lower fertility, semen quality and testosterone levels in selected groups of adults attending andrology clinics. Overall, the observational data in humans are consistent with experimental studies in animals and support the use of AGD as a biomarker of foetal androgen exposure. Future studies evaluating AGD in relation to reproductive hormones in both infants and adults, and to gene polymorphisms, will help to further delineate the effect of prenatal and postnatal androgen exposures on AGD. PMID- 26846873 TI - Ruxolitinib: evolution or revolution in treatment of patients with polycythemia vera? AB - Current treatments for polycythemia vera have remained unchanged for decades with phlebotomy, hydroxycarbamide (also named hydroxyurea) and to a lesser extent interferon being the cornerstones in our therapeutic armamentarium. However, some patients do not respond to, or indeed experience significant side effects to, these current agents and development of alternative therapeutic options is required. Ruxolitinib, a potent JAK1/2 inhibitor, initially approved for myelofibrosis, was recently approved for patients with polycythemia vera refractory or intolerant to hydroxycarbamide. In this article, we review the currently available efficacy and safety data. PMID- 26846872 TI - Nanoquinacrine induced apoptosis in cervical cancer stem cells through the inhibition of hedgehog-GLI1 cascade: Role of GLI-1. AB - To improve the pharmacokinetics and to study the anti-cervical cancer and anti stem cells (CSCs) mechanism of Quinacrine (QC), a spherical nano particle of QC (i.e. NQC) was prepared and characterized. QC and NQC showed higher cytotoxicity in multiple cancer cells than the normal epithelial cells. NQC exhibited more toxicity in cervical cancer cells and its CSCs than QC. A dose-dependent decreased expression of Hedgehog-GLI (HH-GLI) components were noted in NQC treated HeLa cells and its CSCs. NQC increased the expressions of negatively regulated HH-GLI components (GSK3beta, PTEN) and caused apoptosis in CSCs. Reduction of GLI1 at mRNA and promoter level were noted after NQC exposure. The expressions of HH-GLI components, GLI1 promoter activity and apoptosis were unaltered in NQC treated GLI1-knockdown cells. In silico, cell based and in vitro reconstitution assay revealed that NQC inhibit HH-GLI cascade by binding to the consensus sequence (5'GACCACCCA3') of GLI1 in GLI-DNA complex through destabilizing DNA-GLI1 complex. NQC reduced the tumors size and proliferation marker Ki-67 in an in vivo xenograft mice model. Thus, NQC induced apoptosis in cancers through inhibition of HH-GLI cascade by GLI1. Detail interaction of QC DNA-GLI complex can pave path for anticancer drug design. PMID- 26846874 TI - Electroacupuncture improves cognitive function through Rho GTPases and enhances dendritic spine plasticity in rats with cerebral ischemia-reperfusion. AB - The aim of the present study was to evaluate the effect of electroacupuncture (EA) on cognitive function following cerebral ischemia-reperfusion (I/R) injury, and to clarify the mechanism through which Rho GTPase is associated with EA analgesia modulation of dendritic spine plasticity. Rats were randomly divided into three groups: The sham surgery group, the middle cerebral artery occlusion (MCAO) model of ischemia group, and the MCAO with EA (MCAO+EA) treatment group. The MCAO+EA group received treatment with EA at points of Baihui (DU20) and Shenting (DU24) following surgery. It was demonstrated that treatment with EA significantly (P<0.05) protected the cognitive function of rats from impairment caused by cerebral I/R injury. Furthermore, EA treatment increased the density of dendritic spines in the hippocampus of cerebral I/R-injured rats. Simultaneously, EA increased the expression of cell division cycle 42, Ras-related C3 botulinum toxin substrate 1 and F-actin proteins. By contrast, EA treatment inhibited the expression of Ras homologous member A. Collectively, these findings suggest that Rho GTPases and dendritic spine plasticity are critical in mediating the effects of EA treatment at the points of Shenting and Baihui, and that EA protects against impairment of cognitive function following ischemic stroke. PMID- 26846875 TI - Simple and rapid sample preparation system for the molecular detection of antibiotic resistant pathogens in human urine. AB - Antibiotic resistance in urinary tract infections (UTIs) can cause significant complications without quick detection and appropriate treatment. We describe a new approach to capture, concentrate and prepare amplification-ready DNA from antibiotic resistant bacteria in human urine samples. Klebsiella pneumoniae NCTC13443 (bla CTX-M-15 positive) spiked into filtered human urine was used as a model system. Bacteria were captured using anion exchange diaethylaminoethyl (DEAE) magnetic microparticles and concentrated 200-fold within ~3.5 min using a custom, valve-less microfluidic chip. Eight samples were processed in parallel, and DNA was released using heat lysis from an integrated resistive heater. The crude cell lysate was used for real time Recombinase Polymerase Amplification (RPA) of the bla CTX-M-15 gene. The end to end processing time was approximately 15 min with a limit of detection of 1000 bacteria in 1 mL urine. PMID- 26846876 TI - Evolution of GOUNDRY, a cryptic subgroup of Anopheles gambiae s.l., and its impact on susceptibility to Plasmodium infection. AB - The recent discovery of a previously unknown genetic subgroup of Anopheles gambiae sensu lato underscores our incomplete understanding of complexities of vector population demographics in Anopheles. This subgroup, named GOUNDRY, does not rest indoors as adults and is highly susceptible to Plasmodium infection in the laboratory. Initial description of GOUNDRY suggested it differed from other known Anopheles taxa in surprising and sometimes contradictory ways, raising a number of questions about its age, population size and relationship to known subgroups. To address these questions, we sequenced the complete genomes of 12 wild-caught GOUNDRY specimens and compared these genomes to a panel of Anopheles genomes. We show that GOUNDRY is most closely related to Anopheles coluzzii, and the timing of cladogenesis is not recent, substantially predating the advent of agriculture. We find a large region of the X chromosome that has swept to fixation in GOUNDRY within the last 100 years, which may be an inversion that serves as a partial barrier to contemporary gene flow. Interestingly, we show that GOUNDRY has a history of inbreeding that is significantly associated with susceptibility to Plasmodium infection in the laboratory. Our results illuminate the genomic evolution of one of probably several cryptic, ecologically specialized subgroups of Anopheles and provide a potent example of how vector population dynamics may complicate efforts to control or eradicate malaria. PMID- 26846877 TI - Prognostic value of legumain in uveal melanoma. AB - The present study aimed to assess the expression of legumain in uveal melanoma (UM) cell lines and primary UM specimens, and to determine the possible association between legumain expression and clinical as well as pathological characteristics to reveal its impact on the prognosis of patients with UM. Records of primary UM cases treated at Beijing Tongren Hospital and Tianjin Eye Hospital between 1996 and 2005 were retrieved for analysis and a total of 82 patients with uveal melanoma were included in the study. The expression of legumain in the formalin-fixed and paraffin-embedded surgical specimens of these 82 patients was determined using immunohistochemical analysis. In addition, the expression of legumain was examined in two uveal melanoma cell lines using polymerase chain reaction and western blot analyses. The association of legumain expression with clinical/pathological characteristics was analyzed using the chi2 and Fisher's exact test. In addition, the impact of legumain on the prognosis of patients with uveal melanoma was examined. Upregulation of legumain was more predominant in the highly invasive uveal melanoma cell line MUM-2B compared with that in the MUM-2C with low invasiveness. Of 82 primary uveal melanoma tissues, 35 exhibited high expression of legumain, while the other 47 specimens exhibited low or negative expression of legumain. High legumain expression was primarily associated with local invasion of UM. Overall survival analysis revealed that the patients with high legumain expression exhibited poorer survival than patients with low/negative legumain expression. These findings suggested that upregulation of legumain is associated with malignant behavior of UM and that legumain may be used as an negative prognostic factor as well as a therapeutic target. PMID- 26846878 TI - Novel water filtration of saline water in the outermost layer of mangrove roots. AB - The scarcity of fresh water is a global challenge faced at present. Several desalination methods have been suggested to secure fresh water from sea water. However, conventional methods suffer from technical limitations, such as high power consumption, expensive operating costs, and limited system durability. In this study, we examined the feasibility of using halophytes as a novel technology of desalinating high-concentration saline water for long periods. This study investigated the biophysical characteristics of sea water filtration in the roots of the mangrove Rhizophora stylosa from a plant hydrodynamic point of view. R. stylosa can grow even in saline water, and the salt level in its roots is regulated within a certain threshold value through filtration. The root possesses a hierarchical, triple layered pore structure in the epidermis, and most Na(+) ions are filtered at the first sublayer of the outermost layer. The high blockage of Na(+) ions is attributed to the high surface zeta potential of the first layer. The second layer, which is composed of macroporous structures, also facilitates Na(+) ion filtration. This study provides insights into the mechanism underlying water filtration through halophyte roots and serves as a basis for the development of a novel bio-inspired desalination method. PMID- 26846879 TI - No survival benefit associated with routine surveillance imaging for Hodgkin lymphoma in first remission: a Danish-Swedish population-based observational study. AB - The use of routine imaging for patients with classical Hodgkin lymphoma (HL) in complete remission (CR) is controversial. In a population-based study, we examined the post-remission survival of Danish and Swedish HL patients for whom follow-up practices were different. Follow-up in Denmark included routine imaging, usually for a minimum of 2 years, whereas clinical follow-up without routine imaging was standard in Sweden. A total of 317 Danish and 454 Swedish comparable HL patients aged 18-65 years, diagnosed in the period 2007-2012 and having achieved CR following ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)/BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) therapy, were included in the study. The cumulative progression rates in the first 2 years were 4% (95% confidence interval [CI] 1-7) for patients with stage I-II disease vs. 12% (95% CI 6-18) for patients with stage III-IV disease. An imaging-based follow-up practice was not associated with a better post-remission survival in general (P = 0.2) or in stage specific subgroups (P = 0.5 for I-II and P = 0.4 for III-IV). Age >=45 years was the only independent adverse prognostic factor for survival. In conclusion, relapse of HL patients with CR is infrequent and systematic use of routine imaging in these patients does not improve post-remission survival. The present study supports clinical follow-up without routine imaging, as encouraged by the recent Lugano classification. PMID- 26846880 TI - Intravital microscopy of the lung: minimizing invasiveness. AB - In vivo microscopy has recently become a gold standard in lung immunology studies involving small animals, largely benefiting from the democratization of multiphoton microscopy allowing for deep tissue imaging. This technology represents currently our only way of exploring the lungs and inferring what happens in human respiratory medicine. The interest of lung in vivo microscopy essentially relies upon its relevance as a study model, fulfilling physiological requirements in comparison with in vitro and ex vivo experiments. However, strategies developed in order to overcome movements of the thorax caused by breathing and heartbeats remain the chief drawback of the technique and a major source of invasiveness. In this context, minimizing invasiveness is an unavoidable prerequisite for any improvement of lung in vivo microscopy. This review puts into perspective the main techniques enabling lung in vivo microscopy, providing pros and cons regarding invasiveness. PMID- 26846881 TI - The revised guidelines of the Medical Council of India for academic promotions: Need for a rethink. PMID- 26846882 TI - Influence of observable and unobservable exposure on the patient's risk of acquiring influenza-like illness at hospital. AB - During outbreaks of hospital-acquired influenza-like illness (HA-ILI) healthcare workers (HCWs), patients, and visitors are each a source of infection for the other. Quantifying the effects of these various exposures will help improve prevention and control of HA-ILI outbreaks. We estimated the attributability of HA-ILI to: (1) exposure to recorded or unrecorded sources; (2) exposure to contagious patient or contagious HCW; (3) exposure during observable or unobservable contagious period of the recorded sources; and, (4) the moment of exposure. Among recorded sources, 59% [95% credible interval (CrI) 34-83] of HA ILI of patients was associated with exposure to contagious patients and 41% (95% CrI 17-66) with exposure to contagious HCWs. Exposure during the unobservable contagiousness period of source patients accounted for 49% (95% CrI 19-75) of HA ILI, while exposure during the unobservable contagiousness period of source HCWs accounted for 82% (95% CrI 51-99) of HA-ILI. About 80% of HA-ILIs were associated with exposure 1 day earlier. Secondary cases of HA-ILI might appear as soon as the day after the detection of a primary case highlighting the explosive nature of HA-ILI spread. Unobservable transmission was the main cause of HA-ILI transmission suggesting that symptom-based control measures alone might not prevent hospital outbreaks. The results support the rapid implementation of interventions to control influenza transmission. PMID- 26846883 TI - Comparative transcriptomic profiling of hydrogen peroxide signaling networks in zebrafish and human keratinocytes: Implications toward conservation, migration and wound healing. AB - Skin wounds need to be repaired rapidly after injury to restore proper skin barrier function. Hydrogen peroxide (H2O2) is a conserved signaling factor that has been shown to promote a variety of skin wound repair processes, including immune cell migration, angiogenesis and sensory axon repair. Despite growing research on H2O2 functions in wound repair, the downstream signaling pathways activated by this reactive oxygen species in the context of injury remain largely unknown. The goal of this study was to provide a comprehensive analysis of gene expression changes in the epidermis upon exposure to H2O2 concentrations known to promote wound repair. Comparative transcriptome analysis using RNA-seq data from larval zebrafish and previously reported microarray data from a human epidermal keratinocyte line shows that H2O2 activates conserved cell migration, adhesion, cytoprotective and anti-apoptotic programs in both zebrafish and human keratinocytes. Further assessment of expression characteristics and signaling pathways revealed the activation of three major H2O2-dependent pathways, EGF, FOXO1, and IKKalpha. This study expands on our current understanding of the clinical potential of low-level H2O2 for the promotion of epidermal wound repair and provides potential candidates in the treatment of wound healing deficits. PMID- 26846884 TI - The Protective Role of Autophagy in Matrix Metalloproteinase-Mediated Cell Transmigration and Cell Death in High-Glucose-Treated Endothelial Cells. AB - Diabetes mellitus may cause vascular endothelial damage via endothelial matrix metalloproteinase-2 (MMP-2). The role of endothelial autophagy in MMP-2-mediated cell injury in response to high-glucose (HG) stimulation was rarely described. In this study, we used HG-treated human umbilical vein endothelial cells (HUVECs) to investigate the effect of autophagy on MMP-2-induced cell transmigration and apoptosis. THP-1 transmigration was detected by the transmigration assay. Light chain 3 (LC3, representing autophagy), MMP-2, and poly (ADP-ribose) polymerase (PARP, representing apoptosis) of HG (33 mM)-treated HUVECs were evaluated by western blot analysis. The MMP-2 activity was also examined by gelatin zymography. We used GM6001 (10 MUM, an MMP-2 inhibitor) to investigate the relationship of MMP-2 and THP-1 transmigration. Using 3-methyladenine (3MA, 5 mM, an LC3 inhibitor), we explored the effects of autophagy on MMP-2 expression, THP 1 transmigration, and apoptosis. Our results showed that HG increased LC3-II expression, MMP-2 activity, THP-1 transmigration, and cleaved PARP expression in a time-dependent manner (0-48 h); among them, LC3-II appeared earlier (0-24 h) than the others (24-48 h). GM6001 suppressed MMP-2 activity and ameliorated THP-1 transmigration. 3MA suppressed LC3-II expression and increased MMP-2 expression, THP-1 transmigration, and cleaved PARP expression. From these sequential findings, we demonstrated that autophagy plays a protective role in MMP-2 mediated cell transmigration and cell death in HG-stimulated HUVECs. PMID- 26846885 TI - Protective Effects of Nobiletin Against Endotoxic Shock in Mice Through Inhibiting TNF-alpha, IL-6, and HMGB1 and Regulating NF-kappaB Pathway. AB - Nobiletin (NOB), the major bioactive component of polymethoxyflavones in citrus fruits, has been reported possessing significant biological properties. The purpose of the present study was to investigate the protective role of NOB on lipopolysaccharide (LPS)-induced endotoxic shock in mice. We found pretreatment with NOB increases the survival rate of mice after endotoxin injection. The present study clearly demonstrates that pretreatment with NOB decreases the production of early pro-inflammatory cytokines TNF-alpha, IL-6, and late-phase mediator HMGB1 in serum and tissues of kidney, lung, and liver. The histopathological study indicates that NOB administration significantly attenuate tissues injury induced by LPS. Moreover, NOB suppresses the activity of nuclear factor-kappa B (NF-kappaB). These results suggest that NOB protects mice against LPS-induced endotoxic shock through inhibiting the production of TNF-alpha, IL-6, and HMGB1 and the activation of NF-kappaB, which elucidate that NOB may be a promising drug candidate for the treatment of septic shock. PMID- 26846886 TI - Tenuigenin Prevents IL-1beta-induced Inflammation in Human Osteoarthritis Chondrocytes by Suppressing PI3K/AKT/NF-kappaB Signaling Pathway. AB - Tenuigenin (TEN), the main active component of Polygala tenuifolia, has been reported to have anti-inflammatory effects. However, the effects of TEN on IL 1beta-stimulated osteoarthritis chondrocytes have not been reported. The purpose of this study was to investigate the anti-inflammatory effects and mechanism of TEN on IL-1beta-stimulated human osteoarthritis chondrocytes. Human osteoarthritis chondrocytes were pretreated with or without TEN for 1 h and then stimulated with IL-1beta. The production of NO and PGE2 were detected by the Griess reagent and ELISA. The expression of NF-kappaB and MAPKs (p38, JNK, ERK) were measured by Western blot analysis. The production of MMP-1, MMP3, and MMP13 were measured by ELISA. The results showed that treatment of TEN significantly inhibited IL-1beta-induced NO and PGE2 production. TEN also suppressed IL-1beta induced MMP-1, MMP3, and MMP13 expression. Furthermore, TEN was found to inhibit IL-1beta-induced NF-kappaB activation, PI3K, and AKT phosphorylation. In conclusion, these results suggest that TEN inhibits IL-1beta-induced inflammation in human osteoarthritis chondrocytes by inhibiting PI3K/AKT/NF-kappaB signaling pathway. PMID- 26846887 TI - Knockdown of TNFR1 Suppresses Expression of TLR2 in the Cellular Response to Staphylococcus aureus Infection. AB - Osteomyelitis is a common manifestation of invasive Staphylococcus aureus infection characterized by widespread bone loss and destruction. Phagocytes possess various receptors to detect pathogens, including the Toll-like receptors (TLRs). Previous studies have demonstrated that the S. aureus protein SpA binds directly to pre-osteoblastic cells via tumor necrosis factor receptor-1 (TNFR-1). In our present study, we investigated the relationship between TLR2 and TNFR-1 in S. aureus-infected osteoblasts. Our results showed that cell viability decreased, and apoptosis, expression of TLR2, and the secretion of inflammatory cytokines (TNF-alpha and IL-6) increased with increasing concentrations of S. aureus. The JNK pathway was also activated in response to S. aureus infection. Knockdown of TNFR1 not only inhibited the JNK pathway but also reduced TLR2 protein and RANKL levels in S. aureus-infected cells. Inhibition of the JNK pathway reduced the protein level of TLR2 and reduced TNF-alpha and IL-6 secretion in S. aureus infected cells. PMID- 26846889 TI - Rectus sheath and transversus abdominis plane blocks in children: a systematic review and meta-analysis of randomized trials. AB - INTRODUCTION: The role of rectus sheath blocks (RSB) and transversus abdominis plane (TAP) blocks in pediatric surgery has not been well established. OBJECTIVE: We aimed to determine if RSB and TAP blocks decrease postoperative pain and improve recovery in children. DATA SOURCES: Duplicate searching of MEDLINE, EMBASE, Cochrane, Web of Science, and trial registries databases by two reviewers. STUDY SELECTION: Included were randomized trials in children on RSB or TAP block in abdominal operations, excluding inguinal procedures. DATA EXTRACTION: Independent duplicate data extraction and quality assessment using a standardized form. RESULTS: Ten trials met inclusion criteria (n = 599), RSB in five and TAP block in five. A linear mixed effects model on patient level data from three trials showed nerve blocks lowered morphine requirements 6-8 h after surgery, -0.03 mg . kg(-1) (95% CI -0.05, -0.002). Pooled analysis of summary data showed nerve blocks lowered 0-10 scale pain scores immediately after the operation, -0.7 (95% CI -1.3, -0.1); lowered 4-16 scale pain scores, -2.0 (95% CI -2.3, -1.7); and delayed the time to first rescue analgesia, 17 min (95% CI 1.3, 33). Quality assessment showed some studies at moderate to high risk of bias. CONCLUSION: Abdominal wall blocks reduce pain and opiate use in children. We advise cautious interpretation of the results given the heterogeneity of studies. PMID- 26846890 TI - Plant-pollinator interactions in a biodiverse meadow are rather stable and tight for 3 consecutive years. AB - Plant-pollinator interactions can be highly variable across years in natural communities. Although variation in the species composition and its basic structure has been investigated to understand the dynamic nature of pollination networks, little is known about the temporal dynamic of interaction strength between the same plant and pollinator species in any natural community. Pollinator-mediated selection on the evolution of floral traits could be diminished if plant-pollinator interactions vary temporally. To quantify the temporal variation in plant-pollinator interactions and the interaction strength (observed visits), we compared weighted networks between plants and pollinators in a biodiverse alpine meadow in Shangri-La, southwest China for 3 consecutive years. Although plant-pollinator interactions were highly dynamic such that identical interactions only accounted for 10.7% of the total between pair years, the diversity of interactions was stable. These identical interactions contributed 41.2% of total visits and were similar in strength and weighted nestedness. For plant species, 72.6% of species were visited by identical pollinator species between pair years, accounting for over half of the total visits and three-quarters at the functional group level. More generalized pollinators contributed more connectiveness and were more central in networks across years. However, there was no similar or even opposite trend for plant species, which suggested that specialized plant species may also be central in pollinator networks. The variation in pollinator composition decreased as pollinator species numbers increased, suggesting that generalized plants experienced stable pollinator partition. The stable, tight interactions between generalized pollinators and specialized plants represent cornerstones of the studied community. PMID- 26846888 TI - Cryo-EM Data Are Superior to Contact and Interface Information in Integrative Modeling. AB - Protein-protein interactions carry out a large variety of essential cellular processes. Cryo-electron microscopy (cryo-EM) is a powerful technique for the modeling of protein-protein interactions at a wide range of resolutions, and recent developments have caused a revolution in the field. At low resolution, cryo-EM maps can drive integrative modeling of the interaction, assembling existing structures into the map. Other experimental techniques can provide information on the interface or on the contacts between the monomers in the complex. This inevitably raises the question regarding which type of data is best suited to drive integrative modeling approaches. Systematic comparison of the prediction accuracy and specificity of the different integrative modeling paradigms is unavailable to date. Here, we compare EM-driven, interface-driven, and contact-driven integrative modeling paradigms. Models were generated for the protein docking benchmark using the ATTRACT docking engine and evaluated using the CAPRI two-star criterion. At 20 A resolution, EM-driven modeling achieved a success rate of 100%, outperforming the other paradigms even with perfect interface and contact information. Therefore, even very low resolution cryo-EM data is superior in predicting heterodimeric and heterotrimeric protein assemblies. Our study demonstrates that a force field is not necessary, cryo-EM data alone is sufficient to accurately guide the monomers into place. The resulting rigid models successfully identify regions of conformational change, opening up perspectives for targeted flexible remodeling. PMID- 26846891 TI - Strong Photo-Amplification Effects in Flexible Organic Capacitors with Small Molecular Solid-State Electrolyte Layers Sandwiched between Photo-Sensitive Conjugated Polymer Nanolayers. AB - We demonstrate strong photo-amplification effects in flexible organic capacitors which consist of small molecular solid-state electrolyte layers sandwiched between light-sensitive conjugated polymer nanolayers. The small molecular electrolyte layers were prepared from aqueous solutions of tris(8 hydroxyquinoline-5-sulfonic acid) aluminum (ALQSA3), while poly(3-hexylthiophene) (P3HT) was employed as the light-sensitive polymer nanolayer that is spin-coated on the indium-tin oxide (ITO)-coated poly(ethylene terephthalate) (PET) film substrates. The resulting capacitors feature a multilayer device structure of PET/ITO/P3HT/ALQSA3/P3HT/ITO/PET, which were mechanically robust due to good adhesion between the ALQSA3 layers and the P3HT nanolayers. Results showed that the specific capacitance was increased by ca. 3-fold when a white light was illuminated to the flexible organic multilayer capacitors. In particular, the capacity of charge storage was remarkably (ca. 250-fold) enhanced by a white light illumination in the potentiostatic charge/discharge operation, and the photo-amplification functions were well maintained even after bending for 300 times at a bending angle of 180( degrees ). PMID- 26846892 TI - Novel Method for Neuronal Nanosurgical Connection. AB - Neuronal injury may cause an irreversible damage to cellular, organ and organism function. While preventing neural injury is ideal, it is not always possible. There are multiple etiologies for neuronal injury including trauma, infection, inflammation, immune mediated disorders, toxins and hereditary conditions. We describe a novel laser application, utilizing femtosecond laser pulses, in order to connect neuronal axon to neuronal soma. We were able to maintain cellular viability, and demonstrate that this technique is universal as it is applicable to multiple cell types and media. PMID- 26846893 TI - Does Angiotensin-Converting Enzyme Inhibitor and beta-Blocker Use Reduce the Risk of Primary Liver Cancer? A Case-Control Study Using the U.K. Clinical Practice Research Datalink. AB - STUDY OBJECTIVE: It has been suggested that use of the antihypertensive drugs angiotensin-converting enzyme (ACE) inhibitors and beta-blockers may decrease the risk of primary liver cancer; thus, the objective of this study was to evaluate whether use of ACE inhibitors and/or beta-blockers is associated with a lower risk of liver cancer. DESIGN: Nested case-control study. DATA SOURCE: United Kingdom Clinical Practice Research Datalink. PATIENTS: We identified 490 cases with hypertension and a first-time (incident) diagnosis of primary liver cancer between 1988 and 2011. To account for an induction period, the index date was defined as the date of the first recorded liver cancer diagnosis minus 1 year. Controls were selected from patients with hypertension in the CPRD during the study period with a recorded diagnosis of hypertension who had no diagnosis of liver cancer and were free of any other cancer (except nonmelanoma skin cancer) before the index date; they were matched up to a 4:1 ratio to cases based on index date (same index date as that of their matched case), age (same year of birth), sex, general practice, and number of years of recorded history in the CPRD before the index date (1909 controls). Both cases and controls were required to have at least 2 years of recorded activity in the database before the index date. MEASUREMENTS AND MAIN RESULTS: Exposure was defined as receipt of two or more prescriptions for ACE inhibitors and/or beta-blockers before the index date; the reference group was nonuse (0-1 prescription) of ACE or beta-blocker prescriptions before the index date. We also examined the effect of duration of use and, separately, the effect of individual drugs within each medication class on risk of liver cancer, and conducted analyses restricted to patients without liver disease or diabetes mellitus. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). No association was found between use of ACE inhibitors and/or beta-blockers and the risk of liver cancer compared with nonuse (adjusted OR 1.14, 95% CI 0.85-1.55). No significant differences were noted in risk by duration of use or by individual drugs, or after restricting the analyses to patients without diabetes or liver disease. CONCLUSION: Use of ACE inhibitors and/or beta-blockers was not associated with reduced risk of primary liver cancer compared with nonuse of these drugs in persons with hypertension. PMID- 26846894 TI - Dietary sources and sodium intake in a sample of Australian preschool children. AB - OBJECTIVES: To assess dietary sodium intake and the food sources of sodium in a sample of Australian preschool children. DESIGN: Cross-sectional. SETTING: Mothers were followed up when children were approximately 3.5 years of age after participating in a cluster randomised controlled trial: the Melbourne Infant Feeding Activity and Nutrition Trial Program. PARTICIPANTS: 251 Australian children aged 3.5 +/- 0.19 (SD) years. PRIMARY AND SECONDARY OUTCOME MEASURES: The average daily sodium intake was determined using three unscheduled 24 h dietary recalls. The contributions of food groups, core, discretionary and processed foods to daily sodium intake were assessed. RESULTS: The average sodium intake was 1508 +/- 495 (SD) mg/day, (salt equivalent 3.9 +/- 1.3 (SD) g/day) and 87% of children exceeded the Australian Upper Level of Intake (UL) for sodium of 1000 mg/day (salt equivalent 2.6 g/day). Main food sources of sodium were cereal/cereal products (25%), milk products (19%), meat, poultry/game (17%) and cereal-based products (15%). Core foods contributed 65%, and discretionary foods 35% of total daily sodium intake, and within the total diet, minimally processed, processed, processed culinary ingredient and ultraprocessed foods contributed 16%, 35%, 1% and 48% of sodium, respectively. CONCLUSIONS: Within this sample, most children exceeded the recommended UL for sodium. Core and ultraprocessed foods were key sources of sodium which suggests that reductions in the sodium content of these foods are required to reduce sodium intake in young children. These data also provide further support for public health campaigns that seek to reduce consumption of energy-dense, nutrient-poor foods. PMID- 26846895 TI - HandiVIH--A population-based survey to understand the vulnerability of people with disabilities to HIV and other sexual and reproductive health problems in Cameroon: protocol and methodological considerations. AB - INTRODUCTION: In resource-limited countries, people with disabilities seem to be particularly vulnerable to HIV infection due to barriers to accessing information and services, frequent exposure to sexual violence and social exclusion. However, they have often been left behind in the HIV response, probably because of the lack of reliable epidemiological data measuring this vulnerability. Multiple challenges in conducting good quality epidemiological surveys on people with disabilities require innovative methods to better understand the link between disability and HIV. This paper describes how the design and methods of the HandiVIH study were adapted to document the vulnerability of people with disabilities to HIV, and to compare their situation with that of people without disabilities. METHODS AND ANALYSIS: The HandiVIH project aims to combine quantitative and qualitative data. The quantitative component is a cross sectional survey with a control group conducted in Yaounde (Cameroon). A two phase random sampling is used (1) to screen people with disabilities from the general population using the Washington Group questionnaire and, (2) to create a matched control group. An HIV test is proposed to each study participant. Additionally, a questionnaire including a life-event interview is used to collect data on respondents' life-course history of social isolation, employment, sexual partnership, HIV risk factors and fertility. Before the cross-sectional survey, a qualitative exploratory study was implemented to identify challenges in conducting the survey and possible solutions. Information on people with disabilities begging in the streets and members of disabled people's organisations is collected separately. ETHICS AND DISSEMINATION: This study has been approved by the two ethical committees. Special attention has been paid on how to adapt the consenting process to persons with intellectual disabilities. The methodological considerations discussed in this paper may contribute to the development of good practices for conducting quantitative health surveys on people with disabilities. TRIAL REGISTRATION NUMBER: NCT02192658. PMID- 26846897 TI - Systematic review finds major deficiencies in sample size methodology and reporting for stepped-wedge cluster randomised trials. AB - BACKGROUND: Stepped-wedge cluster randomised trials (SW-CRT) are increasingly being used in health policy and services research, but unless they are conducted and reported to the highest methodological standards, they are unlikely to be useful to decision-makers. Sample size calculations for these designs require allowance for clustering, time effects and repeated measures. METHODS: We carried out a methodological review of SW-CRTs up to October 2014. We assessed adherence to reporting each of the 9 sample size calculation items recommended in the 2012 extension of the CONSORT statement to cluster trials. RESULTS: We identified 32 completed trials and 28 independent protocols published between 1987 and 2014. Of these, 45 (75%) reported a sample size calculation, with a median of 5.0 (IQR 2.5 6.0) of the 9 CONSORT items reported. Of those that reported a sample size calculation, the majority, 33 (73%), allowed for clustering, but just 15 (33%) allowed for time effects. There was a small increase in the proportions reporting a sample size calculation (from 64% before to 84% after publication of the CONSORT extension, p=0.07). The type of design (cohort or cross-sectional) was not reported clearly in the majority of studies, but cohort designs seemed to be most prevalent. Sample size calculations in cohort designs were particularly poor with only 3 out of 24 (13%) of these studies allowing for repeated measures. DISCUSSION: The quality of reporting of sample size items in stepped-wedge trials is suboptimal. There is an urgent need for dissemination of the appropriate guidelines for reporting and methodological development to match the proliferation of the use of this design in practice. Time effects and repeated measures should be considered in all SW-CRT power calculations, and there should be clarity in reporting trials as cohort or cross-sectional designs. PMID- 26846896 TI - Postnuclear disaster evacuation and chronic health in adults in Fukushima, Japan: a long-term retrospective analysis. AB - OBJECTIVE: Japan's 2011 Fukushima Daiichi Nuclear Power Plant incident required the evacuation of over a million people, creating a large displaced population with potentially increased vulnerability in terms of chronic health conditions. We assessed the long-term impact of evacuation on diabetes, hyperlipidaemia and hypertension. PARTICIPANTS: We considered participants in annual public health check-ups from 2008 to 2014, administrated by Minamisoma City and Soma City, located about 10-50 km from the Fukushima nuclear plant. METHODS: Disease risks, measured in terms of pre-incident and post-incident relative risks, were examined and compared between evacuees and non-evacuees/temporary-evacuees. We also constructed logistic regression models to assess the impact of evacuation on the disease risks adjusted for covariates. RESULTS: Data from a total of 6406 individuals aged 40-74 years who participated in the check-ups both at baseline (2008-2010) and in one or more post-incident years were analysed. Regardless of evacuation, significant post-incident increases in risk were observed for diabetes and hyperlipidaemia (relative risk: 1.27-1.60 and 1.12-1.30, respectively, depending on evacuation status and post-incident year). After adjustment for covariates, the increase in hyperlipidaemia was significantly greater among evacuees than among non-evacuees/temporary-evacuees (OR 1.18, 95% CI 1.06 to 1.32, p<0.01). CONCLUSIONS: The singularity of this study is that evacuation following the Fukushima disaster was found to be associated with a small increase in long-term hyperlipidaemia risk in adults. Our findings help identify discussion points on disaster planning, including preparedness, response and recovery measures, applicable to future disasters requiring mass evacuation. PMID- 26846898 TI - Surgical trainee research collaboratives in the UK: an observational study of research activity and publication productivity. AB - OBJECTIVES: To analyse the research activity and publication output of surgical trainee research collaboratives in the UK. SETTING: Surgical trainee research collaboratives in the UK. PARTICIPANTS: A total of 24 collaboratives were included in this study from 33 identified organisations. We excluded one group that focused purely on systematic review of the literature and eight groups for which we could not identify suitable data sources (website or trainee committee contact). PRIMARY AND SECONDARY OUTCOME: Primary data-points were identified for each collaborative including surgical subspeciality, numbers and types of projects. For published articles, secondary outcomes including study population size, journal impact factor, number of citations and evidence level were collected. RESULTS: A total of 24 collaboratives met our inclusion criteria with a portfolio of 80 projects. The project types included audit (46%), randomised clinical trial (16%), surveys (16%), cohort studies (10%), systematic reviews (2.5%) and other or unidentifiable (9.5%). A total of 35 publications were identified of which just over half (54%) were original research articles. The median size of studied population was 540 patients with a range from 108 to 3138. The published works provided a varied compilation of evidence levels ranging from 1b (individual RCT) to 5 (expert opinion) with a median level of 2b (individual cohort study). The West Midlands Research Collaborative had the highest number of publications (13), citations (130) and h-index (5). CONCLUSIONS: The experience of UK-based trainee research collaboratives provides useful insights for trainees and policymakers in global healthcare systems on the value and feasibility of trainee-driven high quality surgical research. PMID- 26846899 TI - HIV testing among men who have sex with men in Tijuana, Mexico: a cross-sectional study. AB - OBJECTIVES: HIV testing is critical to the delivery of comprehensive HIV prevention and care services, yet coverage of sexual minorities by HIV testing programmes remains insufficient in many low- and middle-income countries, including Mexico. The objective of this study was to identify the prevalence and correlates of HIV testing among men who have sex with men (MSM) in Tijuana, Mexico. METHODS: We conducted a cross-sectional study (2012-2013) among 189 MSM recruited via respondent-driven sampling (RDS). RDS-weighted logistic regression was used to identify correlates of prior HIV testing. RESULTS: RDS-adjusted prevalence of prior and recent (<= 12 months) HIV testing was 63.5% (95% CI 51.9% to 73.5%) and 36.8% (95% CI 25.4% to 46.4%), respectively. Prior HIV testing was positively associated with older age (adjusted OR (AOR)=1.09, 95% CI 1.04 to 1.15), being born in Tijuana (AOR=2.68, 95% CI 1.05 to 6.86), higher levels of education (AOR=2.65, 95% CI 1.08 to 6.53), identifying as homosexual or gay (AOR=3.73, 95% CI 1.48 to 9.42), being more 'out' about having sex with men (AOR=1.28, 95% CI:1.02 to 1.62), and a history of sexual abuse (AOR=3.24, 95% CI 1.06 to 9.86). Prior HIV testing was negatively associated with reporting more condomless anal intercourse acts (past 2 months) (AOR=0.95, 95% CI 0.92 to 0.98) and greater internalised homophobia (AOR=0.92, 95% CI 0.86 to 0.99). CONCLUSIONS: Our findings indicate an urgent need for expanded HIV testing services for MSM in Tijuana. Innovative, non-stigmatising, confidential HIV testing interventions targeted at young, less educated, migrant and non-gay identifying MSM may facilitate HIV testing and timely linkage to HIV care and treatment within this population. PMID- 26846900 TI - Characterization of Streptococcus pyogenes isolates responsible for adult meningitis in France from 2003 to 2013. AB - Sixty-three cases of Streptococcus pyogenes meningitis in adults were studied. Three predominant emm types were associated with meningitis: emm1 (44%), emm3 (11%), and emm6 (11%). Streptococcal toxic shock syndrome and mortality rates were 40% and 38%, respectively. PMID- 26846901 TI - Atom-Precise Organometallic Zinc Clusters. AB - The bottom-up synthesis of organometallic zinc clusters is described. The cation {[Zn10](Cp*)6 Me}(+) (1) is obtained by reacting [Zn2 Cp*2] with [FeCp2][BAr4 (F)] in the presence of ZnMe2. In the presence of suitable ligands, the high reactivity of 1 enables the controlled abstraction of single Zn units, providing access to the lower-nuclearity clusters {[Zn9 ](Cp*)6} (2) and {[Zn8 ](Cp*)5 ((t) BuNC)3}(+) (3). According to DFT calculations, 1 and 2 can be described as closed shell species that are electron-deficient in terms of the Wade-Mingos rules because the apical ZnCp* units that constitute the cluster cage do not have three, but only one, frontier orbitals available for cluster bonding. Zinc behaves flexibly in building the skeletal metal-metal bonds, sometimes providing one major frontier orbital (like Group 11 metals) and sometimes providing three frontier orbitals (like Group 13 elements). PMID- 26846902 TI - Spinal metastasectomy of renal cell carcinoma: A 16-year single center experience with a minimum 3-year follow-up. AB - BACKGROUND AND OBJECTIVES: Metastasectomy of spinal lesions from renal cell carcinoma (RCC) is a promising strategy. However, its clinical outcome after spinal metastasectomy is unknown owing to the difficulty of curative surgical resection. This is the first study to examine the survival rates of patients who underwent metastasectomy of solitary spinal metastases from RCC. METHODS: A retrospective cohort study of 36 consecutive patients with RCC who underwent nephrectomy and complete removal of solitary spinal lesions between 1995 and 2010 at our institution. Cancer-specific survival (CSS) time from the spinal metastasectomy to death or last follow-up was the main endpoint. Potential factors associated with survival were evaluated with Kaplan-Meier analysis and the long-rank test. RESULTS: For all patients, the estimated median CSS time was 130 months. The 3, 5, and 10-year CSS rates were 77.8%, 69.1%, and 58.0%, respectively, for all patients, and 72.7%, 54.5%, and 27.3%, respectively, for patients with lung metastases at the time of surgery. Only the presence of liver metastases was significantly associated with short-term survival after spinal metastasectomy. CONCLUSIONS: Liver metastases were associated with short-term survival, although lung metastases were not. For selected patients, curative resection of solitary spinal metastases can potentially prolong survival. J. Surg. Oncol. 2016;113:587-592. (c) 2016 Wiley Periodicals, Inc. PMID- 26846903 TI - In silico based investigation of dynamic variations in neprilysin (NEP and NEP2) proteins for extracting the point of specificity. AB - Neprilysin-2 (NEP2) in the central nervous system controls Alzheimer's protein (amyloid-beta) deposition, and prevents its occurrence. However, in the peripheral system, its closest homolog, neutral endopeptidase (NEP), regulates hypertension and heart related diseases. Inhibitors of NEP with a lesser degree of specificity can treat hypertension with an increased risk of cerebral deposition of amyloid-beta. In order to rationalize the point of selectivity, the dynamic behavior of human NEP and NEP2 proteins was monitored by conducting molecular dynamics (MD) simulations. A computationally reliable model of NEP2 was achieved with 79.9%, 19.1% and 0.2% residues in the allowed, additionally allowed and disallowed regions respectively, using as a reference protein. Additionally, molecular docking studies were carried out for a set of five already known inhibitors of NEP and modeled NEP2 to obtain the comparative behaviors of the complexes. MD results highlighted their different responses along with important residues having a part in ligand-protein binding. For substrate and inhibitor binding, Arg664/661 and Zn697/694 were identified as the most conserved residues. High degree flexible transitions during the MD simulations were also observed in loop areas along with active site residues. Energy calculations, hydrogen bonds and their occupancy rates helped to conclude each ligand's potency towards a particular target. In most complexes of hNEP2, the ligands showed weak interactions which might be due to its larger pocket size or huge conformational variations in active site residues upon complexation. In the case of inhibitors of a small size like thiorphan, Arg49 and Arg664 are found to be acting to support the ligand binding in NEP while only Arg661 is acting in NEP2. PMID- 26846904 TI - Transcutaneous carbon dioxide suppresses epithelial-mesenchymal transition in oral squamous cell carcinoma. AB - Oral squamous cell carcinoma (OSCC) is the most common form of oral cancers. Recent studies have shown that the malignant transformation of various carcinomas, including OSCC, is associated with epithelial-mesenchymal transition (EMT), and that expression of the EMT factors are significantly associated with tumor invasion, tumor metastasis, and survival rates in OSCC patients. Hence, there is a possibility that EMT suppression may improve the prognosis of OSCC patients. Hypoxia inducible factor-1alpha (HIF-1alpha) is a crucial microenvironmental factor in tumor progression, which induces the expression of EMT factors. We previously reported that transcutaneous CO2 suppresses both human OSCC tumor growth and metastasis to the regional lymph nodes by improving hypoxia in treated tissue. According to this background, we hypothesized that increased EMT with HIF-1alpha expression may increase the progression and the metastatic potential of OSCC, and that decreased hypoxia by transcutaneous CO2 could suppress EMT. In the present study, in vitro studies showed that hypoxic conditions increased the expression of HIF-1alpha and EMT factors in OSCC cells. In addition, in vivo studies revealed that transcutaneous CO2 increased E cadherin expression with the decreased expression of HIF-1alpha, Snail, Slug, N cadherin, and Vimentin in tumor treatment. These results suggest that transcutaneous CO2 could suppress EMT by improving hypoxia, resulting in the reduction of metastatic potential of OSCC. The findings indicate that transcutaneous CO2 may be able to improve the prognosis of OSCC patients through the suppression of EMT. PMID- 26846906 TI - The spatiotemporal relationship between local Ca(2+) signaling and P2X2R activated membrane blebbing. AB - Mammalian P2X receptors (P2XRs), a family of seven ionotropic purinergic receptors, function as ion channels modulating diverse cellular processes such as secretion, apoptosis and proliferation in response to extracellular ATP. Previously, it was shown that upon ATP stimulus, the P2X7 receptor (a member of P2XR family) triggers plasma membrane (PM) blebbing in HEK293 cells. In this study, we demonstrate that this phenomenon extends to another member of the P2XR family-P2X2 receptor (P2X2R). Similar to P2X7 receptor, P2X2R blebbing is dependent on Ca(2+)-calmodulin and ROCK-I. To elucidate the spatiotemporal relationship between Ca(2+) signaling and blebbing, protein biosensors and switches were used to image and generate Ca(2+) signals, respectively, while observing PM blebbing in cells. Blebbing cannot be initiated by Ca(2+) influx from the endoplasmic reticulum or by Ca(2+) transport across the PM by other Ca(2+) channels. To trigger blebbing, it is necessary for Ca(2+) to enter specifically through the P2X2R. Lastly, a local Ca(2+) signal near a fragment that encodes the intracellular P2X2R C-terminus tail is sufficient to trigger blebbing. PMID- 26846905 TI - Healthcare-associated pneumonia with positive respiratory methicillin-resistant Staphylococcus aureus culture: Predictors of the true pathogenicity. AB - AIM: Although methicillin-resistant Staphylococcus aureus (MRSA) is commonly isolated from respiratory specimens in healthcare-associated pneumonia (HCAP), it is difficult to determine the causative pathogen because of the possibilities of contamination/colonization. The present study aimed to identify clinical predictors of the true pathogenicity of MRSA in HCAP. METHODS: Patients with HCAP with positive MRSA cultures in the sputum or endotracheal aspirates who were admitted to Seirei Mikatahara General Hospital, Hamamatsu, Japan, from 2009 to 2014 were enrolled. According to the administered drugs and the treatment outcomes, patients with true MRSA pneumonia (MP) and those with contamination/colonization of MRSA (false MP) were identified. Baseline characteristics were compared between groups, and clinical predictors of true MP were evaluated by logistic regression analyses. RESULTS: A total of 93 patients (mean age 78.7 +/- 12.6 years) were identified and classified into the true MP (n = 16) or false MP (n = 77) groups. Although baseline characteristics were broadly similar between groups, the true MP group had significantly more patients with PaO2 <= 60 Torr/pulse oximetry saturation <=90% and those with MRSA single cultivation. Both variables were significant predictors of true MP in multivariate analysis (odds ratio of PaO2 <= 60 Torr/pulse oximetry saturation <=90%: 5.64, 95% confidence interval 1.17-27.32; odds ratio of MRSA single cultivation: 4.76, 95% confidence interval 1.22-18.60). CONCLUSIONS: Poor oxygenation and MRSA single cultivation imply the true pathogenicity of MRSA in HCAP with positive respiratory MRSA cultures. The present results might be helpful for the proper use of anti-MRSA drugs in this population. Geriatr Gerontol Int 2017; 17: 456-462. PMID- 26846907 TI - Characterization of published randomized controlled trials assessing clinical pharmacy services around the world. AB - A critical analysis of the research on clinical pharmacy services with regards to study characteristics has not been undertaken since 1998. However, several meta analyses have been conducted to demonstrate the impact of pharmacists' interventions in specific medical conditions. These meta-analyses present high heterogeneity in part because the interventions are poorly and inconsistently described in primary studies. The aim of this article is to present the characteristics of randomized control trials (RCTs) that assess clinical pharmacy services to identify areas of improvement in future pharmacy practice research studies. Different emphasis of research across geographic regions of the world were also examined. During these 40 years, 520 articles reporting 439 RCTs assessing clinical pharmacy services were published. Of the 439 studies, 77.7% (n = 341) were published in the year 2000 or thereafter, 41.46% (n = 182) were conducted in the US, 27.56% (n = 121) in Europe, and 30.98% (n = 136) in the rest of the world. Studies in pharmacy practice have improved in terms of design, with an increase in the number of published RCTs after 2000. However, the small sample size of RCTs is still an issue. After 2000, a significantly higher proportion of studies were conducted in community pharmacy, targeting specific medical conditions, and with a higher number of patients randomized to the intervention group. Conversely, a significantly smaller proportion of studies were conducted in the hospital and targeted a single recipient after 2000. Studies conducted in the US had significantly more intervention arms, focused mostly on a specific medical condition, and were performed in primary care. Different health care systems' organization and policies may influence clinical pharmacy services research across countries. PMID- 26846908 TI - Burning questions: Exploring the impact of natural disasters on community pharmacies. AB - BACKGROUND: The past decade has seen a rapid change in the climate system with an increased risk of extreme weather events. On and following the 3rd of January 2013, Tasmania experienced three catastrophic bushfires, which led to the evacuation of several communities, the loss of many properties, and a financial cost of approximately AUD$80 million. OBJECTIVE: To explore the impacts of the 2012/2013 Tasmanian bushfires on community pharmacies. METHOD: Qualitative research methods were undertaken, employing semi-structured telephone interviews with a purposive sample of seven Tasmanian pharmacists. The interviews were recorded and transcribed, and two different methods were used to analyze the text. The first method utilized Leximancer(r) text analytics software to provide a birds-eye view of the conceptual structure of the text. The second method involved manual, open and axial coding, conducted independently by the two researchers for inter-rater reliability, to identify key themes in the discourse. RESULTS: Two main themes were identified - 'people' and 'supply' - from which six key concepts were derived. The six concepts were 'patients,' 'pharmacists,' 'local doctor,' 'pharmacy operations,' 'disaster management planning,' and 'emergency supply regulation.' CONCLUSION: This study identified challenges faced by community pharmacists during Tasmanian bushfires. Interviewees highlighted the need for both the Tasmanian State Government and the Australian Federal Government to recognize the important primary care role that community pharmacists play during natural disasters, and therefore involve pharmacists in disaster management planning. They called for greater support and guidance for community pharmacists from regulatory and other government bodies during these events. Their comments highlighted the need for a review of Tasmania's three-day emergency supply regulation that allows pharmacists to provide a three-day supply of a patient's medication without a doctor's prescription in an emergency situation. PMID- 26846909 TI - Healthy living champions network: An opportunity for community pharmacy's sustained participation in tackling local health inequalities. AB - BACKGROUND: Evaluations recognize healthy living champions (HLCs) as key contributors to the Health Living Pharmacy (HLP) project's success; the project has served to reduce pressure on family doctor services and clients who would have otherwise not sought professional advice have accessed HLP services. OBJECTIVES: To investigate the impact of innovative networking opportunities in supporting HLCs to function within their role and to explore the network's potential in promoting sustained HLP participation. METHOD: Twenty of Portsmouth's (England) HLCs (n = 33) agreed to participate in focus groups. Transcripts were subjected to interpretative phenomenological analysis guided by grounded theory. The transcripts were read repeatedly; recurrent themes were identified and coded manually and consensus was reached by discussion within the research team. FINDINGS: Network meetings provide HLCs with professional development, networking opportunities and continued encouragement. Recommendations to develop and sustain the network included the formation of a group committee and establishing of a communication facility accessible between meetings. CONCLUSION: The successful Portsmouth HLP project informed the design of UK HLP projects. The current focus is to build a successful strategy to sustain the positive outcomes, building on the recognized enablers. This study contributes further lessons learned to guide health commissioners and service implementers to best support staff development, involvement and motivation through innovative practice. PMID- 26846910 TI - Impact of the Trans-Pacific Partnership Agreement on cost of medicine. PMID- 26846911 TI - Thioredoxin 1 protects astrocytes from oxidative stress by maintaining peroxiredoxin activity. AB - Previous studies have demonstrated that thioredoxin 1 (Trx1) exerts neuroprotective effects against cerebral ischemia/reperfusion injury caused by oxidative stress. While Trx1 is known to maintain the anti-oxidant activity of 2 Cys peroxiredoxins (Prdxs), the underlying mechanisms of its protective effects have remained to be elucidated, which was the aim of the present study. For this, an in vitro ischemic model of hypoxemia lasting for 4 h, followed by 24 h of reperfusion was used. Primary astrocytes from neonatal rats were pre-treated with small interfering RNA targeting Trx1 prior to oxygen glucose deprivation/reperfusion (OGD/R). MTS and lactate dehydrogenase assays were performed to evaluate cell viability. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were employed to assess the mRNA and protein expression levels of Prdx1-4 and Prdx-SO3. Furthermore, a dual luciferase reporter assay was used to assess the interaction between activator protein-1 (AP-1) and Trx1. The present study demonstrated that OGD/R decreased the cell viability and increased cellular damage, which was more marked following Trx1 knockdown. The expression of Prdx1-4 and Prdx-SO3 protein was higher in the cells subjected to OGD/R. Knockdown of Trx1 markedly decreased the levels of Prdx1-4 but increased Prdx-SO3 mRNA and protein levels. The results of the present study also suggested that AP-1 directly activated the expression of Trx1. The present study demonstrated that Trx1 exerts its neuroprotective effects by preventing oxidative stress in astrocytes via maintaining Prdx expression. PMID- 26846912 TI - Commentary on: "Occupational radiation exposure of medical staff performing 90Y loaded microsphere radioembolization". PMID- 26846914 TI - New ways of looking at an old disease: the reimagination of epilepsy. PMID- 26846915 TI - Bilateral orbital pseudotumor in a patient with Takayasu arteritis: a case report and review of the literature. AB - Inflammatory orbital pseudotumor is often associated with rheumatologic disorders. It has been reported commonly with ANCA-associated vasculitides, especially granulomatosis with polyangiitis (Wegener's granulomatosis). There are also a few cases of large vessel vasculitis such as giant cell arteritis and Behcet's disease. Here, we report a patient with undiagnosed Takayasu arteritis presenting with proptosis and diplopia, with later diagnosis of an inflammatory pseudotumor of the orbit. In this case, we believe extensive involvement of blood vessels, including bilateral pulmonary artery stenosis, and elevated inflammatory markers that show disease activity may be related to pseudotumor formation in Takayasu arteritis. Since this is an unusual and unreported presentation of the disease, better estimation of a causal relationship may be possible in the future with further information. In conclusion, although uncommon, this case highlights that orbital pseudotumor may be an important finding in Takayasu arteritis. For early diagnosis, better treatment, and good prognosis, it should be considered in patients presenting with ocular symptoms similar to the other vasculitides. PMID- 26846916 TI - Choice of Antiviral Allocation Scheme for Pandemic Influenza Depends on Strain Transmissibility, Delivery Delay and Stockpile Size. AB - Recently, pandemic response has involved the use of antivirals. These antivirals are often allocated to households dynamically throughout the pandemic with the aim being to retard the spread of infection. A drawback of this is that there is a delay until infection is confirmed and antivirals are delivered. Here an alternative allocation scheme is considered, where antivirals are instead preallocated to households at the start of a pandemic, thus reducing this delay. To compare these two schemes, a deterministic approximation to a novel stochastic household model is derived, which allows efficient computation of key quantities such as the expected epidemic final size, expected early growth rate, expected peak size and expected peak time of the epidemic. It is found that the theoretical best choice of allocation scheme depends on strain transmissibility, the delay in delivering antivirals under a dynamic allocation scheme and the stockpile size. A broad summary is that for realistic stockpile sizes, a dynamic allocation scheme is superior with the important exception of the epidemic final size under a severe pandemic scenario. Our results, viewed in conjunction with the practical considerations of implementing a preallocation scheme, support a focus on attempting to reduce the delay in delivering antivirals under a dynamic allocation scheme during a future pandemic. PMID- 26846913 TI - Clinical use of quantitative cardiac perfusion PET: rationale, modalities and possible indications. Position paper of the Cardiovascular Committee of the European Association of Nuclear Medicine (EANM). AB - Until recently, PET was regarded as a luxurious way of performing myocardial perfusion scintigraphy, with excellent image quality and diagnostic capabilities that hardly justified the additional cost and procedural effort. Quantitative perfusion PET was considered a major improvement over standard qualitative imaging, because it allows the measurement of parameters not otherwise available, but for many years its use was confined to academic and research settings. In recent years, however, several factors have contributed to the renewal of interest in quantitative perfusion PET, which has become a much more readily accessible technique due to progress in hardware and the availability of dedicated and user-friendly platforms and programs. In spite of this evolution and of the growing evidence that quantitative perfusion PET can play a role in the clinical setting, there are not yet clear indications for its clinical use. Therefore, the Cardiovascular Committee of the European Association of Nuclear Medicine, starting from the experience of its members, decided to examine the current literature on quantitative perfusion PET to (1) evaluate the rationale for its clinical use, (2) identify the main methodological requirements, (3) identify the remaining technical difficulties, (4) define the most reliable interpretation criteria, and finally (5) tentatively delineate currently acceptable and possibly appropriate clinical indications. The present position paper must be considered as a starting point aiming to promote a wider use of quantitative perfusion PET and to encourage the conception and execution of the studies needed to definitely establish its role in clinical practice. PMID- 26846917 TI - Development of an Empirically Based Preventive Intervention for Depression in Preadolescent African American Girls. AB - We describe the development, feasibility, and acceptability of a novel preventive intervention for depression in African American girls living in urban poverty. Our approach targeted individual and interpersonal vulnerabilities that have been shown to confer risk for depression in samples of African American girls living in low-income, urban settings, including suppression of negative emotion and lack of assertiveness with peers, memory for positive emotion, active coping, and family connection. Focus groups and an open trial were conducted to refine the goals and mechanisms for skill building. A randomized controlled trial (RCT) of the new program (Cities Mother-Daughter Project) was conducted with 3rd-5th grade students from Chicago Public Schools (CPS). Three cycles of screening, randomization, and deployment were conducted to assess feasibility, satisfaction, and usability. Results indicate that feasibility was weak; whereas, satisfaction and usability were high. Future directions for testing efficacy are discussed. PMID- 26846918 TI - Massilia humi sp. nov. isolated from soil in Incheon, South Korea. AB - A Gram-negative, strictly aerobic, non-motile, rod-shaped bacterium, designated THG-S6.8(T), was isolated from soil in Incheon, South Korea. Based on 16S rRNA gene sequence, strain THG-S6.8(T) was moderately related to Massilia plicata 76(T) (97.3 %), Massilia dura 16(T) (97.2 %) and Massilia albidiflava 45(T) (96.9 %). Chemotaxonomic data revealed that strain THG-S6.8(T) possesses ubiquinone-8 as the predominant respiratory quinone, and summed feature 3 (C16:1 omega7c and/or C16:1 omega6c) and C16:0 as the major fatty acids. The major polar lipids were found to be phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The DNA-DNA relatedness between strain THG-S6.8(T) and Massilia plicata KCTC 12344(T) and Massilia dura KACC 12342(T) was 38.7 and 40.5 %, respectively. The DNA G+C content was 66.8 %. These data, together with phenotypic characterization, suggest the isolate represents a novel species, for which the name Massilia humi sp. nov. is proposed, with THG-S6.8(T) as the type strain (=KCTC 42737(T) = CCTCC AB 2015296(T)). PMID- 26846919 TI - Accuracy of commercially available c-reactive protein rapid tests in the context of undifferentiated fevers in rural Laos. AB - BACKGROUND: C-Reactive Protein (CRP) has been shown to be an accurate biomarker for discriminating bacterial from viral infections in febrile patients in Southeast Asia. Here we investigate the accuracy of existing rapid qualitative and semi-quantitative tests as compared with a quantitative reference test to assess their potential for use in remote tropical settings. METHODS: Blood samples were obtained from consecutive patients recruited to a prospective fever study at three sites in rural Laos. At each site, one of three rapid qualitative or semi-quantitative tests was performed, as well as a corresponding quantitative NycoCard Reader II as a reference test. We estimate the sensitivity and specificity of the three tests against a threshold of 10 mg/L and kappa values for the agreement of the two semi-quantitative tests with the results of the reference test. RESULTS: All three tests showed high sensitivity, specificity and kappa values as compared with the NycoCard Reader II. With a threshold of 10 mg/L the sensitivity of the tests ranged from 87-98 % and the specificity from 91-98 %. The weighted kappa values for the semi-quantitative tests were 0.7 and 0.8. CONCLUSION: The use of CRP rapid tests could offer an inexpensive and effective approach to improve the targeting of antibiotics in remote settings where health facilities are basic and laboratories are absent. This study demonstrates that accurate CRP rapid tests are commercially available; evaluations of their clinical impact and cost-effectiveness at point of care is warranted. PMID- 26846920 TI - Cancer risk in East Asian patients associated with acquired haemolytic anaemia: a nationwide population-based cohort study. AB - BACKGROUND: This study investigated whether patients with acquired haemolytic anaemia (AHA) would have elevated cancer risk including that for non haematological solid tumours. We further examined whether the cancer risk would be different between patients with autoimmune type AHA (AIHA) and patients of non AIHA. METHODS: Using nationwide population-based insurance claims data of Taiwan we identified a cohort of patients with AHA with no pre-existing cancer, (n = 3902) and a comparison cohort (n = 39020) without AHA, frequency-matched by gender, age, urbanization of residency and diagnosis date. Incidence and Cox method estimated adjusted hazard ratios (aHR) of cancers controlling covariates by the end of 2010 were calculated. Risks between patients with AIHA and non-AIHA were compared. Sensitivity analysis was carried out to measure the risk of cancer between patients with and without AHA by follow-up years. RESULTS: Patients with AHA had a 90% greater incidence of cancer than controls, with an aHR of 1.78 (95% confidence interval (CI), 1.50-2.12)]. The overall aHRs of cancer for patients with AIHA and non-AIHA were 2.01 (95% CI, 1.56-2.59) and 1.87 (95% CI, 1.53 2.29), respectively, compared with the comparison cohort. The aHRs for lymphatic haematopoietic malignancy were 19.5 and 9.59 in the AIHA and non-AIHA cohorts, respectively. No hazard of colorectal, lung, liver or breast cancer was significant. CONCLUSIONS: There is a near 2-fold elevated risk for subsequent cancer in patients with AHA, particularly for lymphatic-haematopoietic malignancy, which is much greater for patients with AIHA than non-AIHA. These findings can help clinicians decide patient-centred personalized long-term management. PMID- 26846921 TI - Determinants of basic public health services provision by village doctors in China: using non-communicable diseases management as an example. AB - BACKGROUND: To ensure equity and accessibility of public health care in rural areas, the Chinese central government has launched a series of policies to motivate village doctors to provide basic public health services. Using chronic disease management and prevention as an example, this study aims to identify factors associated with village doctors' basic public health services provision and to formulate targeted interventions in rural China. METHODS: Data was obtained from a survey of village doctors in three provinces in China in 2014. Using a multistage sampling process, data was collected through the self administered questionnaire. The data was then analyzed using multilevel logistic regression models. RESULTS: The high-level basic public health services for chronic diseases (BPHS) provision rate was 85.2% among the 1149 village doctors whom were included in the analysis. Among individual level variables, more education, more training opportunities, receiving more public health care subsidy (OR = 3.856, 95 % CI: 1.937-7.678, and OR = 4.027, 95% CI: 1.722-9.420), being under integrated management (OR = 1.978, 95% CI: 1.132-3.458), and being a New Cooperative Medical Scheme insurance program-contracted provider (OR = 2.099, 95% CI: 1.187-3.712) were associated with the higher BPHS provision by village doctors. Among county level factors, Foreign Direct Investment Index showed a significant negative correlation with BPHS provision, while the government funding for BPHS showed no correlation (P > 0.100). CONCLUSION: Increasing public health care subsidies received by individual village doctors, availability and attendance of training opportunities, and integrated management and NCMS contracting of village clinics are important factors in increasing BPHS provision in rural areas. PMID- 26846922 TI - Preferences for antiviral therapy of chronic hepatitis C: a discrete choice experiment. AB - BACKGROUND: The German Institute for Quality and Efficiency in Health Care (IQWiG) uses patient-relevant outcomes to inform decision-makers. OBJECTIVE: IQWiG conducted a pilot study to examine whether discrete choice experiments (DCEs) can be applied in health economic evaluations in Germany to identify, weight, and prioritize multiple patient-relevant outcomes, using the example of antiviral therapy for chronic hepatitis C (HCV). A further objective was to contribute to a more structured approach towards eliciting and comparing preferences across key stakeholders. METHODS: In autumn 2010, a DCE questionnaire was sent to patients with chronic HCV to estimate preferences across seven outcomes ("attributes"), including treatment efficacy [sustained viral response (SVR) at 6 months], adverse effects (flu-like symptoms, gastrointestinal symptoms, psychiatric symptoms, and skin symptoms/alopecia), and measures of treatment burden (duration of therapy, frequency of injections). A linear model and an effects coded full model were applied to assess the relative importance of the attributes. RESULTS: In total N = 326 patients were included. A clear preference for SVR was shown; frequency of injections and duration of therapy shared the second rank, while psychiatric symptoms ranked third. The duration of flu-like symptoms was the least important attribute. CONCLUSION: Our findings indicate that it is possible to perform a DCE at the national level in a health technology assessment agency. The weighting of multiple outcomes allows an indication-specific and evidence-based measure to be used in health economic evaluations. In decision-making in health care, the approach generally allows for consideration of patient-relevant trade-offs regarding the benefits and harms of medical interventions. PMID- 26846924 TI - Identifying Significant Changes in Cerebrovascular Reactivity to Carbon Dioxide. AB - BACKGROUND AND PURPOSE: Changes in cerebrovascular reactivity can be used to assess disease progression and response to therapy but require discrimination of pathology from normal test-to-test variability. Such variability is due to variations in methodology, technology, and physiology with time. With uniform test conditions, our aim was to determine the test-to-test variability of cerebrovascular reactivity in healthy subjects and in patients with known cerebrovascular disease. MATERIALS AND METHODS: Cerebrovascular reactivity was the ratio of the blood oxygen level-dependent MR imaging response divided by the change in carbon dioxide stimulus. Two standardized cerebrovascular reactivity tests were conducted at 3T in 15 healthy men (36.7 +/- 16.1 years of age) within a 4-month period and were coregistered into standard space to yield voxelwise mean cerebrovascular reactivity interval difference measures, composing a reference interval difference atlas. Cerebrovascular reactivity interval difference maps were prepared for 11 male patients. For each patient, the test retest difference of each voxel was scored statistically as z-values of the corresponding voxel mean difference in the reference atlas and then color-coded and superimposed on the anatomic images to create cerebrovascular reactivity interval difference z-maps. RESULTS: There were no significant test-to-test differences in cerebrovascular reactivity in either gray or white matter (mean gray matter, P = .431; mean white matter, P = .857; paired t test) in the healthy cohort. The patient cerebrovascular reactivity interval difference z-maps indicated regions where cerebrovascular reactivity increased or decreased and the probability that the changes were significant. CONCLUSIONS: Accounting for normal test-to-test differences in cerebrovascular reactivity enables the assessment of significant changes in disease status (stability, progression, or regression) in patients with time. PMID- 26846923 TI - Cytotoxic effects of SMAC-mimetic compound LCL161 in head and neck cancer cell lines. AB - OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) is one of the most common tumor entities worldwide. Unfortunately, recent drug developments in other fields of oncology have yielded no efficacy in the treatment of oral squamous cell carcinoma. As a new starting point, we investigated the impact of Fas ligand (FasL) and the SMAC-mimetic compound LCL161 in mono- and combination treatment in HNSCC cell lines. METHODS: Five different cell lines of HNSCC were treated with FasL and LCL161 in mono- and combination treatment. Cytotoxicity was measured via a crystal violet assay. The cell lines were characterized for CD95 (FasL receptor) expression via flow cytometry. The degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) was detected via Western blot. RESULTS: Incubation with FasL led to a significant decrease in three out of five cell lines. Combination treatment with LCL161 enhanced cytotoxicity significantly. Two cell lines were FasL resistant, but one of them could be resensitized with LCL161. In all cell lines, Western blot analysis showed degradation of cIAP1 after LCL161 application. However, one cell line showed only minor vulnerability to the FasL and LCL161 combination. CONCLUSION: This is the first study investigating combination treatment of FasL and LCL161 in head and neck cancer cell lines. Pro apoptotic effects of the combination were detected in the majority of the cell lines. Interestingly, one of two FasL-resistant cell lines was sensitive to the combination therapy with FasL and LCL161. CLINICAL RELEVANCE: SMAC-mimetic compounds show promising results in the treatment of other tumor entities in vitro and might be useful drugs to improve HNSCC therapy. PMID- 26846925 TI - Automated Hippocampal Subfield Segmentation at 7T MRI. AB - BACKGROUND AND PURPOSE: High resolution 7T MRI is increasingly used to investigate hippocampal subfields in vivo, but most studies rely on manual segmentation which is labor intensive. We aimed to evaluate an automated technique to segment hippocampal subfields and the entorhinal cortex at 7T MRI. MATERIALS AND METHODS: The cornu ammonis (CA)1, CA2, CA3, dentate gyrus, subiculum, and entorhinal cortex were manually segmented, covering most of the long axis of the hippocampus on 0.70-mm(3) T2-weighted 7T images of 26 participants (59 +/- 9 years, 46% men). The automated segmentation of hippocampal subfields approach was applied and evaluated by using leave-one-out cross validation. RESULTS: Comparison of automated segmentations with corresponding manual segmentations yielded a Dice similarity coefficient of >0.75 for CA1, the dentate gyrus, subiculum, and entorhinal cortex and >0.54 for CA2 and CA3. Intraclass correlation coefficients were >0.74 for CA1, the dentate gyrus, and subiculum; and >0.43 for CA2, CA3, and the entorhinal cortex. Restricting the comparison of the entorhinal cortex segmentation to a smaller range along the anteroposterior axis improved both intraclass correlation coefficients (left: 0.71; right: 0.82) and Dice similarity coefficients (left: 0.78; right: 0.77). The accuracy of the automated segmentation versus a manual rater was lower, though only slightly for most subfields, than the intrarater reliability of an expert manual rater, but it was similar to or slightly higher than the accuracy of an expert-versus-manual rater with ~170 hours of training for almost all subfields. CONCLUSIONS: This work demonstrates the feasibility of using a computational technique to automatically label hippocampal subfields and the entorhinal cortex at 7T MRI, with a high accuracy for most subfields that is competitive with the labor-intensive manual segmentation. The software and atlas are publicly available: http://www.nitrc.org/projects/ashs/. PMID- 26846926 TI - Optimal MR Plaque Imaging for Cervical Carotid Artery Stenosis in Predicting the Development of Microembolic Signals during Exposure of Carotid Arteries in Endarterectomy: Comparison of 4 T1-Weighted Imaging Techniques. AB - BACKGROUND AND PURPOSE: Preoperative identification of plaque vulnerability may allow improved risk stratification for patients considered for carotid endarterectomy. The present study aimed to determine which plaque imaging technique, cardiac-gated black-blood fast spin-echo, magnetization-prepared rapid acquisition of gradient echo, source image of 3D time-of-flight MR angiography, or noncardiac-gated spin-echo, most accurately predicts development of microembolic signals during exposure of carotid arteries in carotid endarterectomy. MATERIALS AND METHODS: Eighty patients with ICA stenosis (>=70%) underwent the 4 sequences of preoperative MR plaque imaging of the affected carotid bifurcation and then carotid endarterectomy under transcranial Doppler monitoring of microembolic signals in the ipsilateral middle cerebral artery. The contrast ratio of the carotid plaque was calculated by dividing plaque signal intensity by sternocleidomastoid muscle signal intensity. RESULTS: Microembolic signals during exposure of carotid arteries were detected in 23 patients (29%), 3 of whom developed new neurologic deficits postoperatively. Those deficits remained at 24 hours after surgery in only 1 patient. The area under the receiver operating characteristic curve to discriminate between the presence and absence of microembolic signals during exposure of the carotid arteries was significantly greater with nongated spin-echo than with black-blood fast spin-echo (difference between areas, 0.258; P < .0001), MPRAGE (difference between areas, 0.106; P = .0023), or source image of 3D time-of-flight MR angiography (difference between areas, 0.128; P = .0010). Negative binomial regression showed that in the 23 patients with microembolic signals, the contrast ratio was associated with the number of microembolic signals only in nongated spin-echo (risk ratio, 1.36; 95% confidence interval, 1.01-1.97; P < .001). CONCLUSIONS: Nongated spin-echo may predict the development of microembolic signals during exposure of the carotid arteries in carotid endarterectomy more accurately than other MR plaque imaging techniques. PMID- 26846927 TI - Incidence of Radiologically Isolated Syndrome: A Population-Based Study. AB - BACKGROUND AND PURPOSE: Incidental MR imaging findings resembling MS in asymptomatic individuals, fulfilling the Okuda criteria, are termed "radiologically isolated syndrome." Those with radiologically isolated syndrome are at high risk of their condition converting to MS. The epidemiology of radiologically isolated syndrome remains largely unknown, and there are no population-based studies, to our knowledge. Our aim was to study the population based incidence of radiologically isolated syndrome in a high-incidence region for MS and to evaluate the effect on radiologically isolated syndrome incidence when revising the original radiologically isolated syndrome criteria by using the latest radiologic classification for dissemination in space. MATERIALS AND METHODS: All 2272 brain MR imaging scans in 1907 persons obtained during 2013 in the Swedish county of Vastmanland, with a population of 259,000 inhabitants, were blindly evaluated by a senior radiologist and a senior neuroradiologist. The Okuda criteria for radiologically isolated syndrome were applied by using both the Barkhof and Swanton classifications for dissemination in space. Assessments of clinical data were performed by a radiology resident and a senior neurologist. RESULTS: The cumulative incidence of radiologically isolated syndrome was 2 patients (0.1%), equaling an incidence rate of 0.8 cases per 100,000 person years, in a region with an incidence rate of MS of 10.2 cases per 100,000 person years. There was no difference in the radiologically isolated syndrome incidence rate when applying a modified version of the Okuda criteria by using the newer Swanton classification for dissemination in space. CONCLUSIONS: Radiologically isolated syndrome is uncommon in a high-incidence region for MS. Adapting the Okuda criteria to use the dissemination in space-Swanton classification may be feasible. Future studies on radiologically isolated syndrome may benefit from a collaborative approach to ensure adequate numbers of participants. PMID- 26846928 TI - Modified Core Biopsy Technique to Increase Diagnostic Yields for Well Circumscribed Indeterminate Thyroid Nodules: A Retrospective Analysis. AB - BACKGROUND AND PURPOSE: The results of conventional core biopsy for some thyroid nodules with indeterminate cytology have still remained indeterminate. The aim of this study was to evaluate whether the ultrasonography-guided core needle biopsy technique containing the nodule, capsular portion, and surrounding parenchyma was more effective than a conventional method in enhancing diagnostic yield for circumscribed solid thyroid nodules without malignant sonographic features. MATERIALS AND METHODS: This retrospective comparative study evaluated 26 thyroid nodules in 26 consecutive patients between 2006 and 2010. They were biopsied by using a conventional method, and 61 nodules from 60 patients were biopsied by using a modified ultrasonography-guided core needle biopsy technique in 2013. The patients enrolled in this study presented with circumscribed solid thyroid nodules without malignant sonographic features, classified as nondiagnostic or atypia/follicular lesions of undetermined significance at previous cytology. The ultrasonography-guided core needle biopsy results of the 2 groups were compared. RESULTS: The rate of inconclusive ultrasonography-guided core needle biopsy results was 34.6% (9/26) in the conventional group and 11.4% (7/61) in the modified technique group (P = .018). There was no significant difference in the mean size of the nodules between the 2 groups (P = .134). The malignancy rate was 33% (3/9) for the conventional group and 52% (27/52) for the modified technique group (P = .473). The most common malignant pathology was a follicular variant of papillary thyroid carcinoma and follicular adenoma was the most common benign lesion. CONCLUSIONS: For circumscribed solid nodules without malignant sonographic features with indeterminate cytology, the ultrasonography-guided core needle biopsy technique containing the nodule, capsular portion, and surrounding parenchyma is more effective in diagnostic yield compared with a conventional method that biopsies the intranodular portion. PMID- 26846930 TI - Erratum to: Therapeutic assessment of chloroquine-primaquine combined regimen in adult cohort of Plasmodium vivax malaria from a tertiary care hospital in southwestern India. PMID- 26846929 TI - [Pain assessment in routine care : A prospective observational study in an orthopedic unit]. AB - INTRODUCTION: Although well-established guidelines give advice on how to use analgesics, measure pain, and organize pain treatment, many patients still suffer from avoidable severe pain. We assume one reason for this is that pain is inadequately addressed in routine patient contacts. Thus, we aimed to evaluate the extent to which pain was addressed during patient contacts in routine orthopedic care. MATERIALS AND METHODS: In a prospective observational study in an orthopedic unit of a university hospital, we invited physicians and nurses during their routine patient contacts to be observed by independent, trained monitors. The monitors systematically assessed all pain-related aspects, which were analyzed descriptively afterwards. RESULTS: The monitors documented 572 physician-patient contacts with 7 physicians and 108 patients and 578 nurse patient contacts with 12 nurses and 102 patients. Physicians and nurses asked their patients about pain in 20 and 16 % of the patient contacts, respectively. While in physician-patient contacts, patients most frequently addressed their current pain situation (in 35 % of contacts), in nurse-patient contacts, patients most frequently addressed their need for analgesics (52 %). Patients rated their pain intensity in 16 % of physician-patient contacts vs. 17 % of nurse-patient contacts. CONCLUSIONS: Using a comprehensive external monitoring procedure, we found that systematic pain assessment was not optimally standardized and implemented for systematic, individualized pain therapy by physicians or nurses in our routine care setting. PMID- 26846931 TI - Efficacy of limb salvage with primary tumor resection simultaneously for solitary bone metastasis in limbs. AB - BACKGROUND: This study aims to evaluate the efficacy of limb salvage with primary tumor resection on patients with solitary bone metastasis. METHODS: A retrospective treatment outcome review was performed on 20 patients with solitary bone metastasis as the primary clinical symptom who were admitted to the hospital between 2006 and 2010. With primary tumor resection, 18/20 patients received limb salvage surgery simultaneously. Pain scoring was assessed using the 0 to 10 numerical rating scale. The quality of life scoring was performed before and 3 months after surgery using the SF-30 scoring system. In addition, limb function was assessed 3 months after the operation using the Scoring System of American Musculoskeletal Tumor Society system (MSTS). RESULTS: The pain symptom was significantly ameliorated after the operation (t=26.653, P<0.001), and the quality of life dramatically improved (t=-20.581, P<0.001). The postoperative MSTS scores ranged from 18 to 27. The average score was 23.10+/-2.36. The Kaplan Meier analysis showed that no significant differences (chi2=1.589, P=0.207) were observed in the tumor-free survival time between the wide and marginal resections. CONCLUSIONS: The application of the wide or marginal excision for the primary lesion and bony metastasis focus, based on the principles of primary bone tumors, can significantly relieve the pain and improve the quality of life and limb function of patients whose solitary bone metastasis was manifested as the first sign. PMID- 26846933 TI - Association of Ultrasound Characteristics With Extranodal Extension in Metastatic Papillary Thyroid Carcinoma. AB - IMPORTANCE: The presence of extranodal extension (ENE) in metastatic papillary thyroid carcinoma (PTC) has emerged as an important prognostic factor, independently associated with tumor persistence after initial resection, decreased likelihood of complete biochemical response, and worse cause-specific survival. Therefore, the ability to determine ENE before surgery is desirable and advantageous but to date has not yet been evaluated. OBJECTIVE: To evaluate the use of preoperative ultrasound characteristics in predicting pathologic ENE in patients with metastatic PTC. DESIGN, SETTING, AND PARTICIPANTS: Single institutional, retrospective analysis of patients with metastatic PTC between December 1, 2007, and May 31, 2012. The dates of the analysis were September 1, 2014, to July 31, 2015. Clinicodemographic and histopathologic data were extracted. Preoperative ultrasound images were scored for characteristics of interest by 2 independent radiologists masked to radiology and pathology reports. The setting was an academic tertiary care center. Patients were excluded if they were younger than 18 years, did not have clinical or imaging follow-up after surgery, were found to have histologic diagnoses other than PTC, or were being treated for recurrent disease. EXPOSURES: Preoperative ultrasound and neck dissection. MAIN OUTCOMES AND MEASURES: Association of ultrasound characteristics with ENE. RESULTS: Data from 29 patients with metastatic PTC and available preoperative ultrasound images and pathologic data from neck dissection were included. The patients had a median age at diagnosis of 47 years (age range, 19 85 years); and 76% (22 of 29) were female. Among 29 patients, 11 (38%) had ENE. There were no significant differences in distributions of clinicodemographic or histopathologic characteristics between patients with vs without ENE. The following ultrasound characteristics were significantly associated with ENE positivity: node matting (odds ratio [OR], 6.67; 95% CI, 1.01-44.10; P = .049), presence of node matting or cystic areas (OR, 11.70; 95% CI, 1.85-74.19; P = .009), composite score of 3 or more ultrasound characteristics (OR, 14.00; 95% CI, 2.06-95.09; P = .007), and presence of node matting, perinodal edema, unclear margins, or cystic areas (OR, 10.00; 95% CI, 1.05-95.24; P = .045), as well as presence of node matting, perinodal edema, or unclear margins (OR, 7.07; 95% CI, 1.17-42.85; P = .03). A composite score of 3 or more ultrasound characteristics had the highest accuracy (79.3%) for predicting ENE positivity. CONCLUSIONS AND RELEVANCE: This study identifies preoperative ultrasound characteristics of metastatic PTC that are significantly associated with pathologically determined ENE and supports prospective analyses to further evaluate this use of preoperative ultrasound. PMID- 26846932 TI - Involved-field radiotherapy for esophageal squamous cell carcinoma: theory and practice. AB - Esophageal carcinoma (EC) is characterized by a high rate of lymph node metastasis and its spread pattern is not always predictable. Chemoradiotherapy has an important role in the treatment of EC in both the inoperable and the pre operative settings. However, regarding the target volume for radiation, different clinical practices exist. Theoretically, in addition to the clinical target volume administered to the gross lesion, it might seem logical to deliver a certain dose to the uninvolved regional lymph node area at risk for microscopic disease. However, in practice, it is difficult because of the intolerance of normal tissue to radiotherapy (RT), particularly if all regions containing the cervical, mediastinal, and upper abdominal nodes are covered. To date, the use of elective nodal irradiation (ENI) is still controversial in the field of radiotherapy. Some investigators use involved-field radiotherapy (IFRT) in order to reduce treatment-related toxicities. It is thought that micrometastases can be controlled, to some extent, by chemotherapy and the abscopal effects of radiation. It is the presence of overtly involved lymph nodes rather than the micrometastatic nodes negatively affects survival in patients with EC. In another hand, lymph nodes stationed near primary tumors also receive considerable incidental irradiation doses that may contribute to the elimination of subclinical lesions. These data indicate that an irradiation volume covering only the gross tumor is appropriate. When using ENI or IFRT, very few patients experience solitary regional node failure and out-of-field lymph node failure is not common. Primary tumor recurrence and distant metastases, rather than regional lymph node failure, affect the overall survival in patients with EC. The available evidence indicates that the use of ENI seems to prevent or delay regional nodal relapse rather than improve survival. In a word, these data suggest that IFRT is feasible in EC patients. PMID- 26846935 TI - Photocurrent-generating properties of bulk and few-layered Cd(ii) coordination polymers based on a rigid dicarboxylate ligand. AB - Based on a rigid ligand, 2,5-bis[3'-carboxyl-phenyl] pyridine (H2L), two coordination polymers (CPs) formulated as Cd3L3(DMF)4 (1) and CdL(DMF).DMF (2) were solvothermally synthesized and characterized by single-crystal X-ray diffraction. CP 1 is a uninodal 6-connected 3D network with a {4(4).6(10).8}-mab topology, in which the Cd3 unit with a CdCd separation of 3.61 A is observed. CP 2 exhibits a uninodal 2D layer with a 4(4)-sql topology, in which Cd(ii) ions are linked into a Cd-O-Cd chain with a CdCd separation of 3.91 A. DFT calculations indicate that CP 1 possesses a more narrow band gap than CP 2, and CP 1 yields higher photocurrent density upon visible light illumination than CP 2. In the present work, the few-layered CP 2 has been in situ synthesized, and it shows enhanced photocurrent density with respect to the bulk CP, which is probably associated with the large fraction of uncoordinated surface atoms and dangling bonds in the nanosheet of CP 2. PMID- 26846934 TI - Two-year outcomes after arthroscopic surgery compared to physical therapy for femoracetabular impingement: A protocol for a randomized clinical trial. AB - BACKGROUND: As the prevalence of hip pathology in the younger athletic population rises, the medical community continues to investigate effective intervention options. Femoracetabular impingement is the morphologically abnormal articulation of the femoral head against the acetabulum, and often implicated in pre-arthritic hip conditions of musculoskeletal nature. Arthroscopic surgical decompression and non-surgical rehabilitation programs focused on strengthening and stability are common interventions. However, they have never been directly compared in clinical trials. The primary purpose of this study will be to assess the difference in outcomes between these 2 commonly utilized interventions for femoracetabular impingement. METHODS: The study will be a single site, non-inferiority, randomized controlled trial comparing two different treatment approaches (surgical and nonsurgical) for FAI. The enrollment goal is for a total of 80 subjects with a diagnosis of Femoracetabular impingement that are surgical candidates and have failed 6 weeks of conservative treatment. This will be a convenience sample of consecutive patients that are Tricare beneficiaries and seeking care at Madigan Army Medical Center. Patients that meet the criteria will be screened, provide written consent before enrollment, and then randomized into one of two arms (Group I = hip arthroscopy, Group II = physical therapy). Group I will undergo hip arthroscopy with or without labral repair. Group II will follow an impairment based physical therapy program consisting of 2 sessions per week for 6 weeks. The primary outcome will be the Hip Outcome Score and secondary measures will include the International Hip Outcome Tool and the Global Rating of Change. Measures will be taken at baseline, 6 months, 1 and 2 years. Hip-related healthcare utilization between both groups will also be assessed at the end of 2 years. DISCUSSION: The current evidence to support both surgical and conservative interventions for femoroacetabular impingement is based on low-level research. To date, none of these interventions have been directly compared in a randomized clinical trial. Clinical trials are needed to help establish the value of these interventions in the management of femoracetabular impingement and to help define appropriate clinical pathways. TRIAL REGISTRATION: NCT01993615 30 October 2013. PMID- 26846936 TI - Implementing Multimodality Imaging in the Future. PMID- 26846938 TI - Assessment of Prosthetic Valve Function After TAVR. AB - Calcific aortic valve stenosis is a common valve pathology that increases in prevalence with advancing age. Transcatheter aortic valve (TAV) replacement has now emerged as the preferred treatment for patients at high risk for surgery and for those who are inoperable. However, the use of this ground-breaking technology has inevitably been associated with a host of new problems. These new types of complications are frequently unrecognized or underestimated due to lack of familiarity with the normal and pathological appearance of TAV and often require redefining strategies for diagnosis and treatment. This review presents a systematic approach for follow-up assessment of TAV function, as well as pathology uniquely related to TAV. Because the worldwide transcatheter aortic valve replacement experience has been dominated by the Edwards Sapien (Irvine, California) and Medtronic CoreValve (Minneapolis, Minnesota) family of bioprosthetic aortic valves, we will focus our review on these valves, each with their unique set of advantages and technological challenges. PMID- 26846939 TI - MSCT Identification of Vulnerable Plaque. PMID- 26846940 TI - Are Microcalcification and Hemosiderin Really Limitations of OCT in Detection of TCFA? PMID- 26846937 TI - Noninvasive Cardiovascular Risk Assessment of the Asymptomatic Diabetic Patient: The Imaging Council of the American College of Cardiology. AB - Increased cardiovascular morbidity and mortality in patients with type 2 diabetes is well established; diabetes is associated with at least a 2-fold increased risk of coronary heart disease. Approximately two-thirds of deaths among persons with diabetes are related to cardiovascular disease. Previously, diabetes was regarded as a "coronary risk equivalent," implying a high 10-year cardiovascular risk for every diabetes patient. Following the original study by Haffner et al., multiple studies from different cohorts provided varying conclusions on the validity of the concept of coronary risk equivalency in patients with diabetes. New guidelines have started to acknowledge the heterogeneity in risk and include different treatment recommendations for diabetic patients without other risk factors who are considered to be at lower risk. Furthermore, guidelines have suggested that further risk stratification in patients with diabetes is warranted before universal treatment. The Imaging Council of the American College of Cardiology systematically reviewed all modalities commonly used for risk stratification in persons with diabetes mellitus and summarized the data and recommendations. This document reviews the evidence regarding the use of noninvasive testing to stratify asymptomatic patients with diabetes with regard to coronary heart disease risk and develops an algorithm for screening based on available data. PMID- 26846941 TI - The Authors Reply. PMID- 26846942 TI - IgE-independent pathophysiology of severe atopic dermatitis demonstrated in an IgE-deficient patient. PMID- 26846943 TI - Approaches for characterizing threshold dose-response relationships for DNA damage pathways involved in carcinogenicity in vivo and micronuclei formation in vitro. AB - Assessing the shape of dose-response curves for DNA-damage in cellular systems and for the consequences of DNA damage in intact animals remains a controversial topic. This overview looks at aspects of the pharmacokinetics (PK) and pharmacodynamics (PD) of cellular DNA-damage/repair and their role in defining the shape of dose-response curves using an in vivo example with formaldehyde and in vitro examples for micronuclei (MN) formation with several test compounds. Formaldehyde is both strongly mutagenic and an endogenous metabolite in cells. With increasing inhaled concentrations, there were transitions in gene changes, from activation of selective stress pathway genes at low concentrations, to activation of pathways for cell-cycle control, p53-DNA damage, and stem cell niche pathways at higher exposures. These gene expression changes were more consistent with dose-dependent transitions in the PD responses to formaldehyde in epithelial cells in the intact rat rather than the low-dose linear extrapolation methods currently used for carcinogens. However, more complete PD explanations of non-linear dose response for creation of fixed damage in cells require detailed examination of cellular responses in vitro using measures of DNA damage and repair that are not easily accessible in the intact animal. In the second section of the article, we illustrate an approach from our laboratory that develops fit for-purpose, in vitro assays and evaluates the PD of DNA damage and repair through studies using prototypical DNA-damaging agents. Examination of a broad range of responses in these cells showed that transcriptional upregulation of cell cycle control and DNA repair pathways only occurred at doses higher than those causing overt damage fixed damage-measured as MN formation. Lower levels of damage appear to be handled by post-translational repair process using pre existing proteins. In depth evaluation of the PD properties of one such post translational process (formation of DNA repair centers; DRCs) has indicated that the formation of DRCs and their ability to complete repair before replication are consistent with threshold behaviours for mutagenesis and, by extension, with chemical carcinogenesis. PMID- 26846944 TI - Clinical, mineral and ultrastructural changes in carious dentin of primary molars after restoration. AB - INTRODUCTION: Partial caries removal has been shown to be an effective method to treat deep carious lesions in deciduous teeth. Nevertheless, the possibility of keeping infected dentin in the cavity still requires additional investigation. The objective of this research was to describe changes in primary infected dentin after restoration with glass ionomer cement. METHODS: Dentin from 45 primary molars with deep and active carious lesions was evaluated using clinical and laboratory criteria, before and 60 days after restoration. The clinical analysis evaluated dentin colour (CO), dentin consistency (COS) and laser fluorescence (LF). The laboratory procedures assessed bacterial contamination and mineral content (MC), and evaluated the dentin ultrastructure and collagen content. Data on CO, COS, LF and colony forming units were analysed using the Wilcoxon signed rank test; MC, bacterial counts and collagen evaluations were evaluated using the Student's t-test. RESULTS: After 60 days, lower values of LF were observed, together with a lower bacterial count, and a higher COS was found, with an increase in calcium, phosphorus and collagen contents. Differences were not detected for CO or for fluorine content. Baseline samples showed enlarged tubules with bacterial invasion; 60-day samples showed better organised tissue, with a more compact intertubular dentin and narrower tubules. CONCLUSION: It is concluded that appropriate cavity sealing can promote beneficial changes in deep carious lesions of primary teeth, even in the presence of infected dentin. PMID- 26846945 TI - SPRINT: To Whom Do the Results Apply? PMID- 26846947 TI - The Time Has Come to Define Centers of Excellence in Mitral Valve Repair. PMID- 26846946 TI - Effect of Recurrent Mitral Regurgitation Following Degenerative Mitral Valve Repair: Long-Term Analysis of Competing Outcomes. AB - BACKGROUND: The risk for and consequences of recurrent mitral regurgitation (MR) following degenerative mitral valve repair are poorly understood. OBJECTIVES: This study sought to examine recurrent MR risk along with reoperation and survival rates. METHODS: We evaluated patients undergoing primary mitral repair for isolated degenerative MR over 1 decade. Median follow-up was 11.5 years (interquartile range: 9.2 to 13.6 years) and was 99% complete. Multivariate analysis of post-repair MR recurrence employed Cox proportional hazards and multistate modeling. RESULTS: A total of 1,218 patients met the study criteria; the mean age was 64 +/- 13 years, mean ejection fraction was 63 +/- 9%, and 864 (71%) patients were men. Prolapse was posterior in 62%, bileaflet in 26%, and anterior in 12%. The 15-year incidence of recurrent MR (i.e., MR >=2) was 13.3%, incidence of mitral reoperation was 6.9%, and overall mortality was 44.0%. Repair before 1996 independently predicted MR recurrence (hazard ratio: 1.52). Additional determinants were: age, mild intraoperative residual MR, anterior leaflet prolapse, bileaflet prolapse, perfusion time >90 min, and lack of annuloplasty. Recurrence of moderate or greater MR was associated with adverse left ventricular remodeling and increased likelihood of death (hazard ratio: 1.72). Among those undergoing repair after 1996, MR recurrence rate was 1.5 per 100 patient-years during the first year post-repair, decreasing markedly to 0.9 thereafter. CONCLUSIONS: Our study demonstrated that recurrent MR following degenerative mitral valve repair is associated with adverse left ventricular remodeling and late death. The incidence of MR recurrence decreases markedly following the first year after intervention. A transparent discussion of recurrent MR risk has pressing relevance when referring patients with complex mitral valve prolapse. PMID- 26846948 TI - U.S. Hospital Use of Echocardiography: Insights From the Nationwide Inpatient Sample. AB - BACKGROUND: Increased use of echocardiography (echo) raises questions of whether echo is an overused diagnostic procedure in the United States. OBJECTIVES: This study investigated national trends, practice patterns, and patient outcomes associated with inpatient echo use reported in the Nationwide Inpatient Sample (NIS). METHODS: We identified admission diagnoses most commonly associated with echo use and performed multivariate logistic regression within each diagnosis cohort to assess whether echo use was associated with all-cause inpatient mortality. Secondary analysis was performed within our institution to validate use trends identified in the NIS database. RESULTS: Between 2001 and 2011, the absolute volume and incidence of echo steadily increased at average annual rates of 3.41% and 3.04%, respectively. In 2010, the use of echo was associated with lower odds of inpatient mortality among hospitalizations for acute myocardial infarction (adjusted odds ratio [OR]: 0.74; 95% confidence interval [CI]: 0.63 to 0.86; p < 0.001), cardiac dysrhythmia (adjusted OR: 0.72; 95% CI: 0.55 to 0.94; p = 0.02), acute cerebrovascular disease (adjusted OR: 0.36; 95% CI: 0.31 to 0.42; p < 0.001), congestive heart failure (adjusted OR: 0.82; 95% CI: 0.72 to 0.94; p = 0.005), and sepsis (adjusted OR: 0.77; 95% CI: 0.70 to 0.85; p < 0.001). In 2010, these 5 diagnoses accounted for 3.7 million hospital admissions (9% of all hospitalizations); however, echo was reported in only 8% of cases. Secondary analysis of imaging practices at our institution confirmed underuse of echo among patients who died during hospitalization for indications identified in the NIS database. CONCLUSIONS: Despite increasing rates of performance, echo may be underused during critical cardiovascular hospitalizations. PMID- 26846949 TI - Are We Doing Too Many Inpatient Echocardiograms?: The Answer From Big Data May Surprise You! PMID- 26846950 TI - Biallelic Truncating Mutations in ALPK3 Cause Severe Pediatric Cardiomyopathy. AB - BACKGROUND: Cardiomyopathies are usually inherited and predominantly affect adults, but they can also present in childhood. Although our understanding of the molecular basis of pediatric cardiomyopathy has improved, the underlying mechanism remains elusive in a substantial proportion of cases. OBJECTIVES: This study aimed to identify new genes involved in pediatric cardiomyopathy. METHODS: The authors performed homozygosity mapping and whole-exome sequencing in 2 consanguineous families with idiopathic pediatric cardiomyopathy. Sixty unrelated patients with pediatric cardiomyopathy were subsequently screened for mutations in a candidate gene. First-degree relatives were submitted to cardiac screening and cascade genetic testing. Myocardial samples from 2 patients were processed for histological and immunohistochemical studies. RESULTS: We identified 5 patients from 3 unrelated families with pediatric cardiomyopathy caused by homozygous truncating mutations in ALPK3, a gene encoding a nuclear kinase that plays an essential role in early differentiation of cardiomyocytes. All patients with biallelic mutations presented with severe hypertrophic and/or dilated cardiomyopathy in utero, at birth, or in early childhood. Three patients died from heart failure within the first week of life. Moreover, 2 of 10 (20%) heterozygous family members showed hypertrophic cardiomyopathy with an atypical distribution of hypertrophy. Deficiency of alpha-kinase 3 has previously been associated with features of both hypertrophic and dilated cardiomyopathy in mice. Consistent with studies in knockout mice, we provide microscopic evidence for intercalated disc remodeling. CONCLUSIONS: Biallelic truncating mutations in the newly identified gene ALPK3 give rise to severe, early-onset cardiomyopathy in humans. Our findings highlight the importance of transcription factor pathways in the molecular mechanisms underlying human cardiomyopathies. PMID- 26846951 TI - Pediatric Cardiomyopathy: New Insight Into Potential Disease Mechanisms. PMID- 26846953 TI - Diversifying Our Ranks: A Call to Action. PMID- 26846952 TI - Testosterone and Cardiovascular Disease. AB - Testosterone (T) is the principal male sex hormone. As men age, T levels typically fall. Symptoms of low T include decreased libido, vasomotor instability, and decreased bone mineral density. Other symptoms may include depression, fatigue, erectile dysfunction, and reduced muscle strength/mass. Epidemiology studies show that low levels of T are associated with more atherosclerosis, coronary artery disease, and cardiovascular events. However, treating hypogonadism in the aging male has resulted in discrepant results in regard to its effect on cardiovascular events. Emerging studies suggest that T may have a future role in treating heart failure, angina, and myocardial ischemia. A large, prospective, long-term study of T replacement, with a primary endpoint of a composite of adverse cardiovascular events including myocardial infarction, stroke, and/or cardiovascular death, is needed. The Food and Drug Administration recently put additional restrictions on T replacement therapy labeling and called for additional studies to determine its cardiac safety. PMID- 26846954 TI - Sudden Cardiac Death in Asia and China: Are We Different? PMID- 26846955 TI - If You're Not at the Table, You're on the Menu: A Rallying Cry for Fellows-in Training. PMID- 26846956 TI - Investigator-Reported Bleeding Versus Post Hoc Adjudication of Bleeding: Lessons From the CHAMPION PHOENIX Trial. PMID- 26846957 TI - Enhanced Adventitial Vasa Vasorum Formation in Patients With Vasospastic Angina: Assessment With OFDI. PMID- 26846958 TI - Survival Differences in Clinical Trials With Long-Term Follow-Up. PMID- 26846959 TI - Reply: Survival Differences in Clinical Trials With Long-Term Follow-up. PMID- 26846960 TI - Precision Medicine, Obstructive Sleep Apnea, and Refractory Hypertension. PMID- 26846961 TI - Reply: Precision Medicine, Obstructive Sleep Apnea, and Refractory Hypertension. PMID- 26846962 TI - Evolution of Plasticity: Mechanistic Link between Development and Reversible Acclimation. AB - Phenotypic characteristics of animals can change independently from changes in the genetic code. These plastic phenotypic responses are important for population persistence in changing environments. Plasticity can be induced during early development, with persistent effects on adult phenotypes, and it can occur reversibly throughout life (acclimation). These manifestations of plasticity have been viewed as separate processes. Here we argue that developmental conditions not only change mean trait values but also modify the capacity for acclimation. Acclimation counteracts the potentially negative effects of phenotype-environment mismatches resulting from epigenetic modifications during early development. Developmental plasticity is therefore also beneficial when environmental conditions change within generations. Hence, the evolution of reversible acclimation can no longer be viewed as independent from developmental processes. PMID- 26846963 TI - Unveiling Secrets of Overcoming the "Heteroatom Problem" in Palladium-Catalyzed Aerobic C-H Functionalization of Heterocycles: A DFT Mechanistic Study. AB - Directed C-H functionalization of heterocycles through an exocyclic directing group (DG) is challenging due to the interference of the endocyclic heteroatom(s). Recently, the "heteroatom problem" was circumvented with the development of the protection-free Pd-catalyzed aerobic C-H functionalization of heterocycles guided by an exocyclic CONHOMe DG. We herein provide DFT mechanistic insights to facilitate the expansion of the strategy. The transformation proceeds as follows. First, the Pd2(dba)3 precursor interacts with t-BuNC (L, one of the substrates) and O2 to form the L2Pd(II)-eta(2)-O2 peroxopalladium(II) species that can selectively oxidize N-methoxy amide (e.g., PyCONHOMe) substrate, giving an active L2Pd(II)X2 (X = PyCONOMe) species and releasing H2O2. After t-BuNC ligand migratory insertion followed by a 1,3-acyl migration and association with another t-BuNC, L2Pd(II)X2 converts to a more stable C-amidinyl L2Pd(II)XX' (X' = PyCON(t-Bu)C?NOMe) species. Finally, L2Pd(II)XX' undergoes C-H activation and C-C reductive elimination, affording the product. The C-H activation is the rate determining step. The success of the strategy has three origins: (i) the N methoxy amide DG can be easily oxidized in situ to generate the active L2Pd(II)X2 species via the oxidase pathway, thus preventing the destructive oxygenase pathway leading to stable t-BuNCO or the O-bridged dimeric Pd(II) species. The methoxy group in this amide DG greatly facilitates the oxidase pathway, and the tautomerization of N-methoxy amide to its imidic acid tautomer makes the oxidation of the substrate even easier. (ii) The X group in L2Pd(II)X2 can serve as an internal base to promote the C-H activation via CMD (concerted metalation deprotonation) mechanism. (iii) The strong coordination ability of t-BuNC substrate/ligand suppresses the conventional cyclopalladation pathway enabled by the coordination of an endocyclic heteroatom to the Pd-center. PMID- 26846965 TI - Evaluation of the subtraction method utilizing posterior view for improving visibility of the sentinel lymph nodes for lymphoscintigraphy in breast cancer. AB - OBJECTIVE: This study aimed to evaluate the usefulness of the subtraction method for improving sentinel lymph node (SLN) visibility by reducing scattering near the injection site. METHODS: Images of two phantoms for the injection site and SLNs built using an original design were simultaneously acquired using a dual head camera equipped with a low-energy high-resolution collimator on the lower detector (posterior view) and a low-energy general-purpose collimator on the upper detector (anterior view). Subtraction method images were created by subtracting the posterior view from the anterior view, the latter of which was designated as the conventional method. Image contrast was calculated from the counts of regions of interest placed on the two phantoms of the injection site and SLNs. SLNs visibility to a distance from the injection site and a radioactivity ratio based on the injection site (15 MBq) was evaluated by image contrast and visual interpretation. RESULTS: The best improvement in contrast occurred at a distance of 20 pixels (1.08 mm/pixel) from the injection site, and improved further as the lymph node radioactivity was smaller. The SLN's visibility corresponding to a distance of 20 pixels improved significantly (p < 0.001), from 1/2560 of radioactivity at the injection site (approximately 6 kBq) to 1/640 (approximately 23 kBq), and the SLN was only detectable using the subtraction method. The SLN (1/5120, approximately 3 kBq) was difficult to detect even with the subtraction method, whereas the SLN with a ratio >=1/320 (approximately 46 kBq) was easily detected even with the conventional method. These visibilities did not differ significantly between the two methods (p = 0.16 and >0.32, respectively). The subtraction method could detect SLNs near the tumor on clinical images. CONCLUSIONS: The subtraction method improved SLN visibility near the injection site by reducing scattering from the injection site. Furthermore, an advantage of the subtraction method is that it does not require additional imaging, because the posterior view is obtained simultaneously and utilized. PMID- 26846964 TI - CABeRNET: a Cytoscape app for augmented Boolean models of gene regulatory NETworks. AB - BACKGROUND: Dynamical models of gene regulatory networks (GRNs) are highly effective in describing complex biological phenomena and processes, such as cell differentiation and cancer development. Yet, the topological and functional characterization of real GRNs is often still partial and an exhaustive picture of their functioning is missing. RESULTS: We here introduce CABERNET, a Cytoscape app for the generation, simulation and analysis of Boolean models of GRNs, specifically focused on their augmentation when a only partial topological and functional characterization of the network is available. By generating large ensembles of networks in which user-defined entities and relations are added to the original core, CABERNET allows to formulate hypotheses on the missing portions of real networks, as well to investigate their generic properties, in the spirit of complexity science. CONCLUSIONS: CABERNET offers a series of innovative simulation and modeling functions and tools, including (but not being limited to) the dynamical characterization of the gene activation patterns ruling cell types and differentiation fates, and sophisticated robustness assessments, as in the case of gene knockouts. The integration within the widely used Cytoscape framework for the visualization and analysis of biological networks, makes CABERNET a new essential instrument for both the bioinformatician and the computational biologist, as well as a computational support for the experimentalist. An example application concerning the analysis of an augmented T helper cell GRN is provided. PMID- 26846966 TI - Aspirin Enhances Osteogenic Potential of Periodontal Ligament Stem Cells (PDLSCs) and Modulates the Expression Profile of Growth Factor-Associated Genes in PDLSCs. AB - BACKGROUND: This study investigates the effects of aspirin (ASA) on the proliferative capacity, osteogenic potential, and expression of growth factor associated genes in periodontal ligament stem cells (PDLSCs). METHODS: Mesenchymal stem cells (MSCs) from PDL tissue were isolated from human premolars (n = 3). The MSCs' identity was confirmed by immunophenotyping and trilineage differentiation assays. Cell proliferation activity was assessed through 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Polymerase chain reaction array was used to profile the expression of 84 growth factor-associated genes. Pathway analysis was used to identify the biologic functions and canonic pathways activated by ASA treatment. The osteogenic potential was evaluated through mineralization assay. RESULTS: ASA at 1,000 MUM enhances osteogenic potential of PDLSCs. Using a fold change (FC) of 2.0 as a threshold value, the gene expression analyses indicated that 19 genes were differentially expressed, which includes 12 upregulated and seven downregulated genes. Fibroblast growth factor 9 (FGF9), vascular endothelial growth factor A (VEGFA), interleukin-2, bone morphogenetic protein-10, VEGFC, and 2 (FGF2) were markedly upregulated (FC range, 6 to 15), whereas pleotropin, FGF5, brain-derived neurotrophic factor, and Dickkopf WNT signaling pathway inhibitor 1 were markedly downregulated (FC 32). Of the 84 growth factor-associated genes screened, 35 showed high cycle threshold values (>=35). CONCLUSIONS: ASA modulates the expression of growth factor associated genes and enhances osteogenic potential in PDLSCs. ASA upregulated the expression of genes that could activate biologic functions and canonic pathways related to cell proliferation, human embryonic stem cell pluripotency, tissue regeneration, and differentiation. These findings suggest that ASA enhances PDLSC function and may be useful in regenerative dentistry applications, particularly in the areas of periodontal health and regeneration. PMID- 26846967 TI - Anti-Inflammatory and Osteoprotective Effects of Cannabinoid-2 Receptor Agonist HU-308 in a Rat Model of Lipopolysaccharide-Induced Periodontitis. AB - BACKGROUND: Anti-inflammatory and immunologic properties of cannabinoids have been reported in several tissues. Expression of cannabinoid receptor Type 2 was reported in osteoblasts and osteoclasts, suggesting a key role in bone metabolism. The aim of this study is to assess the effect of treatment with cannabinoid-2 receptor agonist HU-308 in the oral health of rats subjected to lipopolysaccharide (LPS)-induced periodontitis. METHODS: Twenty-four rats were distributed in four groups (six rats per group): 1) control rats; 2) sham rats; 3) rats submitted to experimental periodontitis (LPS); and 4) rats submitted to experimental periodontitis and treated with HU-308 (LPS+HU). In groups LPS and LPS+HU, periodontitis was induced by LPS (1 mg/mL) injected into the gingival tissue (GT) of maxillary and mandibular first molars and into the interdental space between the first and second molars, 3 days per week for 6 weeks. In group LPS+HU, HU-308 (500 ng/mL) was applied topically to the GT daily. RESULTS: Alveolar bone loss resulting from LPS-induced periodontitis was significantly attenuated with HU-308 treatment (LPS+HU), measured by macroscopic and histologic examination. Treatment also reduced gingival production of inflammatory mediators augmented in LPS-injected rats, such as: 1) inducible nitric oxide (iNOS) activity (LPS: 90.18 +/- 36.51 pmol/minute/mg protein versus LPS+HU: 16.37 +/- 4.73 pmol/minute/mg protein; P <0.05); 2) tumor necrosis factor alpha (LPS: 185.70 +/- 25.63 pg/mg protein versus LPS+HU: 95.89 +/- 17.47 pg/mg protein; P <0.05); and 3) prostaglandin E2 (PGE2) (LPS: 159.20 +/- 38.70 pg/mg wet weight versus LPS+HU: 71.25 +/- 17.75 pg/mg wet weight; P <0.05). Additionally, HU-308 treatment prevented the inhibitory effect of LPS-induced periodontitis on the salivary secretory response to pilocarpine. Moreover, iNOS activity and PGE2 content, which were increased by LPS-induced periodontitis in the submandibular gland, returned to control values after HU-308 treatment. CONCLUSION: This study demonstrates anti-inflammatory, osteoprotective, and prohomeostatic effects of HU 308 in oral tissues of rats with LPS-induced periodontitis. PMID- 26846968 TI - Vascular Fragility and the Endothelial Glycocalyx in the Tissues Lining the Healthy Gingival Crevice. AB - BACKGROUND: The aim of this study is to investigate vascular fragility and endothelial glycocalyx (ECG) in images of the healthy gingival crevice (GC). The ECG is a surface layer lining the luminal walls of blood vessels composed of proteoglycans and glycoproteins with other components. Degradation of the layer has been shown to drastically affect microvascular flow, permeability, and immune function. METHODS: Videomicroscopic images from tissues lining the healthy GC in 20 healthy volunteers were analyzed to determine the presence of microhemorrhage related to branched dilated microvessels. Imaging of capillary ECG in human labial mucosa was achieved by the use of a 1-mm-diameter 0.5 numerical aperture gradient index objective lens and one-sided oblique illumination using light at 450 nm. This allows resolution of red blood cells within the capillary and the endothelial cell wall of the lumen. The cell-free plasma gap between the red cell and endothelial wall represents the ECG. RESULTS: In the healthy GC there was no evidence of microhemorrhage in participants that had only simple capillary loops (seven of 20). Microhemorrhage was present in the majority of participants with branched dilated microvessels (11 of 13) (McNemar Test for equal distribution, P = 0.05). A cell-free plasma gap representing the ECG could be imaged in the superficial tissues lining the labial sulcus. No such cell-free plasma gap could be detected in the branched dilated microvessels in tissues lining the GC. CONCLUSIONS: There is an association between the presence of vascular microhemorrhage and branched dilated microvessels in the tissues lining the clinically healthy GC. Loss of ECG might be part of the inflammatory process in these tissues. PMID- 26846969 TI - An ARXPS and ERXPS study of quaternary ammonium and phosphonium ionic liquids: utilising a high energy Ag Lalpha' X-ray source. AB - A series of ammonium- and phosphonium-based ionic liquids have been probed using X-ray photoelectron spectroscopy (XPS) with a high energy Ag Lalpha' X-ray source. The capability of the Ag Lalpha' X-ray source for ionic liquid analysis is confirmed alongside the characterisation of previously undetected high energy core photoelectron emissions. Additionally, the utilisation of the Ag Lalpha' X ray source as a depth profiling technique (ERXPS) to investigate the structure of the ionic liquid/vacuum interface has been demonstrated, with comparison made to angle resolved X-ray photoelectron spectroscopy (ARXPS). PMID- 26846970 TI - Microbiologically Influenced Corrosion of 2707 Hyper-Duplex Stainless Steel by Marine Pseudomonas aeruginosa Biofilm. AB - Microbiologically Influenced Corrosion (MIC) is a serious problem in many industries because it causes huge economic losses. Due to its excellent resistance to chemical corrosion, 2707 hyper duplex stainless steel (2707 HDSS) has been used in the marine environment. However, its resistance to MIC was not experimentally proven. In this study, the MIC behavior of 2707 HDSS caused by the marine aerobe Pseudomonas aeruginosa was investigated. Electrochemical analyses demonstrated a positive shift in the corrosion potential and an increase in the corrosion current density in the presence of the P. aeruginosa biofilm in the 2216E medium. X-ray photoelectron spectroscopy (XPS) analysis results showed a decrease in Cr content on the coupon surface beneath the biofilm. The pit imaging analysis showed that the P. aeruginosa biofilm caused a largest pit depth of 0.69 MUm in 14 days of incubation. Although this was quite small, it indicated that 2707 HDSS was not completely immune to MIC by the P. aeruginosa biofilm. PMID- 26846971 TI - Facing the Time Window in Acute Ischemic Stroke: The Infarct Core. AB - BACKGROUND: Increasing numbers needed to treat within the first hours after ischemic stroke onset indicate a strong time dependency of the viability of brain tissue. However, this time dependency is not reflected in recent randomized controlled trials of endovascular stroke treatment. This study evaluates whether and to which extent a time dependency exists in patients with embolic carotid T or M1 occlusions within the first 6 h of stroke onset. METHODS: Patient data were retrieved from the Freiburg stroke data bank. Time from onset to acquisition of the diffusion weighted images (DWIs) varied between 49 and 357 min. Ischemic lesions were semiautomatically segmented on apparent diffusion coefficient maps with a threshold of 600 * 10 (- 6) mm(2)/s. Occlusion location and thrombus length were determined with magnetic resonance angiography, T2*, and more recently susceptibility weighted image (SWI) sequences. A hyperintense vessel sign in FLAIR images as a possible surrogate for collaterals was also identified. RESULTS: A total of 155 patients with occlusions of the carotid T (n = 26), proximal M1 segment (n = 44), and distal M1 segment (n = 85) of the middle cerebral artery between 2011 and 2015 were included. Infarct volumes varied from 0.3 to 180.2 mL. Infarct size did not correlate with stroke onset to DWI times. Infarct volumes also did not associate with different locations of vessel occlusion, thrombus length, presence of the hyperintense vessel sign and initial infarct growth. CONCLUSION: We found no significant time dependency of the viability of brain tissue with embolic carotid T or M1 occlusions between 1 and 6 h after stroke onset. The early infarction volume is thus probably determined in the hyperacute phase by the quality of leptomeningeal collaterals and comparatively stable in this time period. PMID- 26846972 TI - Upregulation of metastasis-associated PRL-3 initiates chordoma in zebrafish. AB - The metastasis-associated phosphatase of regenerating liver-3 (PRL-3) plays multiple roles in progression of various human cancers; however, significance of its role during development has not been addressed. Here we cloned and characterized the expression pattern of zebrafish prl-3 transcript and showed that it is ubiquitiously expressed in the first 24 h of development with both maternal and zygotic expressions. The transcripts become progressively restricted to the notochord, vessels and the intestine by 96 h post-fertilization. Notably, overexpression of zebrafish Prl-3 (zPrl-3) and human PRL-3 induces notochord malformation in zebrafish. This phenotype resembles chordoma and is confirmed by associated misexpression of notochord-specific markers. Clinical significance of the PRL-3 in chordoma is strongly suggested by detection of PRL-3 antigen in clinical chordoma specimens. Collectively, our results uncovered that aberrant overexpression of PRL-3 could initiate chordoma in early development and suggest the use of PRL-3 could be used as a predictor and a therapeutic target for chordoma. PMID- 26846973 TI - The Effect of Midline Corset Platysmaplasty on Degree of Face-lift Flap Elevation During Concomitant Deep-Plane Face-lift: A Cadaveric Study. AB - IMPORTANCE: The evaluation of the effects of midline platysmaplasty concomitant with rhytidectomy. OBJECTIVE: To determine whether midline platysmaplasty limits the degree of lift during deep-plane face-lift. DESIGN, SETTING, AND PARTICIPANTS: Deep-plane rhytidectomy was performed on 10 cadaveric hemifaces. The redundant skin for excision after performing the face-lift was measured with and without midline platymaplasty. EXPOSURES: Deep-plane rhytidectomy. MAIN OUTCOMES AND MEASURES: The redundant skin was measured preauricularly in the vertical and horizontal dimension, and postauricularly after deep-plane face-lift and after adding a midline platysmaplasty. RESULTS: Concomitant midline platysmaplasty significantly reduced the amount of lift during concomitant deep plane rhytidectomy preauricularly in the vertical dimension by 40.5% (from 37.0 mm excess skin redraped to 22.0 mm) and postauricularly by 23.9% (from 40.6 mm excess skin redraped to 30.9 mm) (P < .001 and P < .001, respectively). The 19.7% reduction in the horizontal skin redraping after midline platysmaplasty (from 14.7 mm excess skin redraped to 11.8 mm) did not reach statistical significance (P = .15). CONCLUSIONS AND RELEVANCE: Concomitant midline corset platysmaplasty significantly limits the ability to lift the neck as well as the jawline and midface during rhytidectomy. LEVEL OF EVIDENCE: NA. PMID- 26846974 TI - Traumatic Dental Injuries in the primary dentition: a 15-year bibliometric analysis of Dental Traumatology. AB - AIM: To explore the profile of articles on traumatic dental injuries (TDI) in the primary dentition published in Dental Traumatology in the last 15 years using bibliometric analysis. METHODS: Three researchers read all titles and abstracts of articles published in Dental Traumatology between 2000 and 2014 (excluding editorials and letters) and selected all articles on TDI in the primary dentition. The articles were categorized according to year of publication, country in which the study was conducted, study design, and topics addressed. Divergences were resolved by consensus between the researchers. RESULTS: Among a total of 1257 articles published, 98 were initially excluded. Among the remaining 1159 articles, 152 (13.1%) focused on TDI in the primary dentition. The articles were conducted in 29 countries, with Brazil (38.8%) and Turkey (11.8%) accounting for the largest numbers. Cross-sectional studies (36.2%) and case report/case series (33.6%) were the most frequent study designs. Only two systematic reviews were published. The most commonly addressed topics were frequency/etiology/associated factors (36.8%), treatment (30.9%), and prognosis (19.7%). Among the articles addressing treatment, two-thirds were case reports or case series. The effects of TDI in primary teeth on their permanent successors were addressed in 20.4% of the articles (31/152). CONCLUSIONS: The number of articles on TDI in the primary dentition has increased, but remains low. The evaluation of study designs and topics addressed identified gaps that could contribute to the development of new studies on TDI in the primary dentition, especially cohort studies that evaluate risk factors, prognosis, and treatment. PMID- 26846976 TI - Erratum: The pan-class I phosphatidyl-inositol-3 kinase inhibitor NVP-BKM120 demonstrates anti-leukemic activity in acute myeloid leukemia. PMID- 26846975 TI - Clinical Cancer Advances 2016: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology. PMID- 26846977 TI - Discovery and verification of urinary peptides in type 2 diabetes mellitus with kidney injury. AB - Varying degrees of renal injury could lead to different changes in urinary protein composition. We want to find urinary candidate peptide biomarkers in type 2 diabetic patients with different extents of kidney injury. Two sets of patients were recruited. Discovery set: weak cationic-exchange magnetic beads coupled with matrix-assisted laser desorption ionization time-of-flight mass spectrometry were used to profile the low-molecular weight peptidome in urine samples from type 2 diabetes patients with normoalbuminura and microalbuminuria. The differently expressed urinary peptides were screened by ClinProTools2.1 bioinformatics software and identified through nano-liquid chromatography-tandem mass spectrometry. Verification set: the above screened urinary peptides were validated by use matrix-assisted laser desorption ionization time-of-flight mass spectrometry on another group of type 2 diabetes patients with different extents use of kidney injury. In the screening and identification stages, seven urinary peptides were selected as the most promising biomarker candidates, and they were identified as fragments of vitronectin precursor, isoform 1 of fibrinogen alpha chain precursor, prothrombin precursor and inter-alpha-trypsin inhibitor heavy chain H4. The diagnostic efficacy of these urinary peptides was evaluated by area under the receiver operating characteristic curve, and they were 0.767, 0.768, 0.868, 0.910, 0.860, 0.843, and 0.865, respectively. In the verification stage, m/z 1743.9, 2154, 2175.5, and 2184.9 were decreased as albumin-to-creatinine (Alb/Cre) increased and m/z 2231.1, 2430.8, and 2756.1 were elevated as Alb/Cre rose. These small molecule peptides are related to type 2 diabetes kidney damage, and they may play an important role in monitoring type 2 diabetes. PMID- 26846978 TI - Antitumor effects of galectin-3 inhibition in human renal carcinoma cells. AB - Galectins are thought to be prognosticators for survival in renal cell cancer. However, the biological activity of galectin-3 (Gal-3) in renal carcinoma cells is still debated. In this study, immunohistochemical staining confirmed a high expression of Gal-3 in tumor tissue from renal cell carcinoma. Critically, Gal-3 expression was related to tumor cell differentiation. Consistent with Gal-3 expression in renal cell cancer, strong expression of Gal-3 was also observed in several renal tumor cell lines but not in normal renal cells. A Gal-3 high expression cell line Caki-1 was chosen to study the biological activity of Gal-3. Using short hairpin RNA method, Gal-3 expression in Caki-1 cells was knocked down. We evidenced that Gal-3 knockdown inhibited cell proliferation and invasion, induced Caspase-3-dependent apoptosis and arrested cell cycle at G1 phase. Mechanically, Cyclin D1 expression decreased, but p27 increased after Gal 3 knockdown. Taken together, these results suggest that Gal-3 is related to the development of renal cell cancer and could serve as a target to therapy renal cell cancer. PMID- 26846979 TI - Role of leaf hydraulic conductance in the regulation of stomatal conductance in almond and olive in response to water stress. AB - The decrease of stomatal conductance (gs) is one of the prime responses to water shortage and the main determinant of yield limitation in fruit trees. Understanding the mechanisms related to stomatal closure in response to imposed water stress is crucial for correct irrigation management. The loss of leaf hydraulic functioning is considered as one of the major factors triggering stomatal closure. Thus, we conducted an experiment to quantify the dehydration response of leaf hydraulic conductance (Kleaf) and its impact on gs in two Mediterranean fruit tree species, one deciduous (almond) and one evergreen (olive). Our hypothesis was that a higher Kleaf would be associated with a higher gs and that the reduction in Kleaf would predict the reduction in gs in both species. We measured Kleaf in olive and almond during a cycle of irrigation withholding. We also compared the results of two methods to measure Kleaf: dynamic rehydration kinetics and evaporative flux methods. In addition, determined gs, leaf water potential (Psileaf), vein density, photosynthetic capacity and turgor loss point. Results showed that gs was higher in almond than in olive and so was Kleaf (Kmax = 4.70 and 3.42 mmol s(-1) MPa(-1) m(-2), in almond and olive, respectively) for Psileaf > -1.2 MPa. At greater water stress levels than -1.2 MPa, however, Kleaf decreased exponentially, being similar for both species, while gs was still higher in almond than in olive. We conclude that although the Kleaf decrease with increasing water stress does not drive unequivocally the gs response to water stress, Kleaf is the variable most strongly related to the gs response to water stress, especially in olive. Other variables such as the increase in abscisic acid (ABA) may be playing an important role in gs regulation, although in our study the gs-ABA relationship did not show a clear pattern. PMID- 26846980 TI - Photoperiod and temperature constraints on the relationship between the photochemical reflectance index and the light use efficiency of photosynthesis in Pinus strobus. AB - The photochemical reflectance index (PRI) is a proxy for the activity of the photoprotective xanthophyll cycle and photosynthetic light use efficiency (LUE) in plants. Evergreen conifers downregulate photosynthesis in autumn in response to low temperature and shorter photoperiod, and the dynamic xanthophyll cycle mediated non-photochemical quenching (NPQ) is replaced by sustained NPQ. We hypothesized that this shift in xanthophyll cycle-dependent energy partitioning during the autumn is the cause for variations in the PRI-LUE relationship. In order to test our hypothesis, we characterized energy partitioning and pigment composition during a simulated summer-autumn transition in a conifer and assessed the effects of temperature and photoperiod on the PRI-LUE relationship. We measured gas exchange, chlorophyll fluorescence and leaf reflectance during the photosynthetic downregulation in Pinus strobus L. seedlings exposed to low temperature/short photoperiod or elevated temperature/short photoperiod conditions. Shifts in energy partitioning during simulated autumn were observed when the pools of chlorophylls decreased and pools of photoprotective carotenoids increased. On a seasonal timescale, PRI was controlled by carotenoid pool sizes rather than xanthophyll cycle dynamics. Photochemical reflectance index variation under cold autumn conditions mainly reflected long-term pigment pool adjustments associated with sustained NPQ, which impaired the PRI-LUE relationship. Exposure to warm autumn conditions prevented the induction of sustained NPQ but still impaired the PRI-LUE relationship. We therefore conclude that alternative zeaxanthin-independent NPQ mechanisms, which remain undetected by the PRI, are present under both cold and warm autumn conditions, contributing to the discrepancy in the PRI-LUE relationship during autumn. PMID- 26846981 TI - The distribution of epidermolysis bullosa in Australia with a focus on rural and remote areas. AB - BACKGROUND/OBJECTIVES: Patients with epidermolysis bullosa (EB) require specialised medical care. In Australia this expertise is located in the major cities, with patients living in rural and remote areas having reduced access to these services. We aim to analyse the geographical distribution of patients with EB in Australia to determine the relevance of this potential geographical disadvantage for this population. METHODS: Using postal codes obtained from the Australian National Diagnostic Laboratory Database for EB and the Australasian EB Registry, living patients with EB in Australia were categorised using the Australian standard geographical classification, remoteness areas. An analysis of EB subtype, including severity was also performed. RESULTS: A total of 318 patients were categorised, of whom 221 lived in major cities, 65 in inner regional areas, 26 in outer regional areas, four in remote and two in very remote areas. Half the patients living in remote and very remote areas had severe forms of EB. CONCLUSIONS: A significant proportion of patients with EB live outside the major cities in Australia. Half of the patients living in remote and very remote areas had severe forms of EB. Targeted strategies to improve access to EB specific medical care may be needed for patients living in rural and remote areas. PMID- 26846982 TI - Removal of oxyfluorfen from ex-situ soil washing fluids using electrolysis with diamond anodes. AB - In this research, firstly, the treatment of soil spiked with oxyfluorfen was studied using a surfactant-aided soil-washing (SASW) process. After that, the electrochemical treatment of the washing liquid using boron doped diamond (BDD) anodes was performed. Results clearly demonstrate that SASW is a very efficient approach in the treatment of soil, removing the pesticide completely by using dosages below 5 g of sodium dodecyl sulfate (SDS) per Kg of soil. After that, complete mineralization of organic matter (oxyflourfen, SDS and by-products) was attained (100% of total organic carbon and chemical oxygen demand removals) when the washing liquids were electrolyzed using BDD anodes, but the removal rate depends on the size of the particles in solution. Electrolysis of soil washing fluids occurs via the reduction in size of micelles until their complete depletion. Lower concentrations of intermediates are produced (sulfate, chlorine, 4-(trifluoromethyl)-phenol and ortho-nitrophenol) during BDD-electrolyzes. Finally, it is important to indicate that, sulfate (coming from SDS) and chlorine (coming from oxyfluorfen) ions play an important role during the electrochemical organic matter removal. PMID- 26846983 TI - Phytoplankton communities of polar regions--Diversity depending on environmental conditions and chemical anthropopressure. AB - The polar regions (Arctic and Antarctic) constitute up to 14% of the biosphere and offer some of the coldest and most arid Earth's environments. Nevertheless several oxygenic phototrophs including some higher plants, mosses, lichens, various algal groups and cyanobacteria, survive that harsh climate and create the base of the trophic relationships in fragile ecosystems of polar environments. Ecosystems in polar regions are characterized by low primary productivity and slow growth rates, therefore they are more vulnerable to disturbance, than those in temperate regions. From this reason, chemical contaminants influencing the growth of photoautotrophic producers might induce serious disorders in the integrity of polar ecosystems. However, for a long time these areas were believed to be free of chemical contamination, and relatively protected from widespread anthropogenic pressure, due their remoteness and extreme climate conditions. Nowadays, there is a growing amount of data that prove that xenobiotics are transported thousands of kilometers by the air and ocean currents and then they are deposed in colder regions and accumulate in many environments, including the habitats of marine and freshwater cyanobacteria. Cyanobacteria (blue green algae), as a natural part of phytoplankton assemblages, are globally distributed, but in high polar ecosystems they represent the dominant primary producers. These microorganisms are continuously exposed to various concentration levels of the compounds that are present in their habitats and act as nourishment or the factors influencing the growth and development of cyanobacteria in other way. The most common group of contaminants in Arctic and Antarctic are persistent organic pollutants (POPs), characterized by durability and resistance to degradation. It is important to determine their concentrations in all phytoplankton species cells and in their environment to get to know the possibility of contaminants to transfer to higher trophic levels, considering however that some strains of microalgae are capable of metabolizing xenobiotics, make them less toxic or even remove them from the environment. PMID- 26846985 TI - Natural history of age-related lobular involution and impact on breast cancer risk. AB - Age-related lobular involution (LI) is a physiological process in which the terminal duct lobular units of the breast regress as a woman ages. Analyses of breast biopsies from women with benign breast disease (BBD) have found that extent of LI is negatively associated with subsequent breast cancer development. Here we assess the natural course of LI within individual women, and the impact of progressive LI on breast cancer risk. The Mayo Clinic BBD cohort consists of 13,455 women with BBD from 1967 to 2001. The BBD cohort includes 1115 women who had multiple benign biopsies, 106 of whom had developed breast cancer. Within this multiple biopsy cohort, the progression of the LI process was examined by age at initial biopsy and time between biopsies. The relationship between LI progression and breast cancer risk was assessed using standardized incidence ratios and by Cox proportional hazards analysis. Women who had multiple biopsies were younger age and had a slightly higher family history of breast cancer as compared with the overall BBD cohort. Extent of LI at subsequent biopsy was greater with increasing time between biopsies and for women age 55 + at initial biopsy. Among women with multiple biopsies, there was a significant association of higher breast cancer risk among those with involution stasis (lack of progression, HR 1.63) as compared with those with involution progression, p = 0.036. The multiple biopsy BBD cohort allows for a longitudinal study of the natural progression of LI. The majority of women in the multiple biopsy cohort showed progression of LI status between benign biopsies, and extent of progression was highest for women who were in the perimenopausal age range at initial biopsy. Progression of LI status between initial and subsequent biopsy was associated with decreased breast cancer risk. PMID- 26846986 TI - Molecular subtype profiling of invasive breast cancers weakly positive for estrogen receptor. AB - The estrogen receptor (ER) is a key predictive biomarker in the treatment of breast cancer. There is uncertainty regarding the use of hormonal therapy in the setting of weakly positive ER by immunohistochemistry (IHC). We report intrinsic subtype classification on a cohort of ER weakly positive early-stage breast cancers. Consecutive cases of breast cancer treated by primary surgical resection were retrospectively identified from 4 centers that engage in routine external proficiency testing for breast biomarkers. ER-negative (Allred 0 and 2) and ER weakly positive (Allred 3-5) cases were included. Gene expression profiling was performed using qRT-PCR. Intrinsic subtype prediction was made based upon the PAM50 gene expression signature. 148 cases were included in the series: 60 cases originally diagnosed as ER weakly positive and 88 ER negative. Of the cases originally assessed as ER weakly positive, only 6 (10 %) were confirmed to be of luminal subtype by gene expression profiling; the remaining 90 % of cases were classified as basal-like or HER2-enriched subtypes. This was not significantly different than the fraction of luminal cases identified in the IHC ER-negative cohort (5 (5 %) luminal, 83(95 %) non-luminal). Recurrence-free, and overall, survival rates were similar in both groups (p = 0.4 and 0.5, respectively) despite adjuvant hormonal therapy prescribed in the majority (59 %) of weakly positive ER cases. Weak ER expression by IHC is a poor correlate of luminal subtype in invasive breast cancer. In the setting of highly sensitive and robust IHC methodology, cutoffs for ER status determination and subsequent systemic therapy should be revisited. PMID- 26846987 TI - Perfusion reduction in the absence of structural differences in cognitively impaired versus unimpaired RRMS patients. AB - BACKGROUND: Cognitive impairment affects 40%-68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS. METHODS: Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant. RESULTS: No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale-Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04). CONCLUSION: Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences. PMID- 26846988 TI - Hyperconnectivity of the dorsolateral prefrontal cortex following mental effort in multiple sclerosis patients with cognitive fatigue. AB - OBJECTIVE: To investigate the dynamic temporal changes of brain resting-state functional connectivity (RS-FC) following mental effort in multiple sclerosis (MS) patients with cognitive fatigue (CF). METHODS: Twenty-two MS patients, 11 with (F) and 11 without CF, and 12 healthy controls were included. Separate RS-FC scans were acquired on a 3T MR scanner immediately before (t0), immediately after (t1) and 30 minutes after (t2) execution of the paced auditory serial addition test (PASAT), a cognitively demanding task. Subjectively perceived CF after PASAT execution was also assessed. RS-FC changes were investigated by using a data driven approach (the Intrinsic Connectivity Contrast-power), complemented by a priori defined regions of interest analyses. RESULTS: The F-group patients experienced stronger RS-FC at t2 between the left superior frontal gyrus (L-SFG) and occipital, frontal and temporal areas, which increased over time after PASAT execution. In the F-group patients, the L-SFG was hyperconnected at t1 with the left caudate nucleus and hypoconnected at t2 with the left anterior thalamus. These variations were correlated with both subjectively perceived and clinically assessed CF, and-for the left thalamus-with PASAT performance. CONCLUSION: The development of cortico-cortical and cortico-subcortical hyperconnectivity following mental effort is related to CF symptoms in MS patients. PMID- 26846989 TI - Fatigue in multiple sclerosis: The contribution of occult white matter damage. AB - BACKGROUND: A functional cortico-subcortical disconnection has been recognized in fatigued multiple sclerosis (MS) patients. Normal appearing white matter (NAWM) damage might contribute to the abovementioned disconnectivity. OBJECTIVES: To assess the relationship between fatigue and microstructural NAWM damage in relapsing-remitting (RR) MS. METHODS: Sixty RRMS patients and 29 healthy controls (HC) underwent a magnetic resonance imaging (MRI) protocol including diffusion tensor imaging (DTI). Patients with a mean Fatigue Severity Scale (FSS) score ? 4 were considered fatigued (fatigued MS (F-MS)). Tract-based spatial statistics were applied for voxel-wise analysis of DTI indices. A correlation analysis was performed between FSS score and DTI indices in the entire MS group. RESULTS: Thirty MS patients were F-MS. Compared to HC, F-MS patients showed a more extensive NAWM damage than not fatigued MS (NF-MS) patients, with additional damage in the following tracts: frontal and occipital juxtacortical fibers, external capsule, uncinate fasciculus, forceps minor, superior longitudinal fasciculus, cingulum, and pons. No differences were found between F-MS and NF-MS patients. Fatigue severity correlated to DTI abnormalities of corona radiata, cingulum, corpus callosum, forceps minor, superior longitudinal fasciculus, inferior fronto-occipital fasciculus, thalamus and anterior thalamic radiation, cerebral peduncle, and midbrain. CONCLUSIONS: Fatigue is associated to a widespread microstructural NAWM damage, particularly in associative tracts connected to frontal lobes. PMID- 26846990 TI - Patterns of insecticide resistance and knock down resistance (kdr) in malaria vectors An. arabiensis, An. coluzzii and An. gambiae from sympatric areas in Senegal. AB - BACKGROUND: Malaria vector control in Africa relies on insecticides targeting adult mosquito vectors via insecticide treated nets or indoor residual spraying. Despite the proven efficacy of these strategies, the emergence and rapid rise in insecticide resistance in malaria vectors raises many concerns about their sustainability. Therefore, the monitoring of insecticide resistance is essential for resistance management strategies implementation. We investigated the kdr mutation frequencies in 20 sympatric sites of An. arabiensis Patton, An. coluzzii Coetzee & Wilkerson and An. gambiae Giles and its importance in malaria vector control by evaluating the susceptibility to insecticides in four representative sites in Senegal. METHODS: Sibling species identification and kdr mutation detection were determined using polymerase chain reaction on mosquitoes collected using pyrethrum sprays collection in 20 sites belonging to two transects with differential insecticide selection pressure. The World Health Organization (WHO) tube test was used to determine phenotypic resistance of An. gambiae s.l. to DDT, deltamethrin, lambdacyholothrin, permethrin, bendiocarb and malathion in four representative sites. RESULTS: The L1014F kdr mutation was widely distributed and was predominant in An. gambiae in comparison to An. arabiensis and An. coluzzii. The bioassay tests showed a general trend with a resistance to DDT and pyrethroids and a susceptibility to organophosphate and carbamate according to WHO thresholds. For deltamethrin and permethrin, the two most used insecticides, no significant difference were observed either between the two transects or between mortality rates suggesting no differential selection pressures on malaria vectors. The study of the KD times showed similar trends as comparable levels of resistance were observed, the effect being more pronounced for permethrin. CONCLUSIONS: Our study showed a widespread resistance of malaria vectors to DDT and pyrethroids and a widespread distribution of the 1014F kdr allele. These combined observations could suggest the involvement of the kdr mutation. The existence of other resistance mechanisms could not be ruled out as a proportion of mosquitoes did not harbour the kdr allele whereas the populations were fully resistant. The susceptibility to carbamate and organophosphate could be exploited as alternative for insecticide resistance management. PMID- 26846984 TI - The Sertoli cell: one hundred fifty years of beauty and plasticity. AB - It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular 'nurse cell', not only a key cell in the testis, but indeed one of the most amazing cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell's role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways. PMID- 26846991 TI - The Plasminogen Activation System Promotes Dendritic Spine Recovery and Improvement in Neurological Function After an Ischemic Stroke. AB - Advances in neurocritical care and interventional neuroradiology have led to a significant decrease in acute ischemic stroke (AIS) mortality. In contrast, due to the lack of an effective therapeutic strategy to promote neuronal recovery among AIS survivors, cerebral ischemia is still a leading cause of disability in the world. Ischemic stroke has a harmful impact on synaptic structure and function, and plasticity-mediated synaptic recovery is associated with neurological improvement following an AIS. Dendritic spines (DSs) are specialized dendritic protrusions that receive most of the excitatory input in the brain. The deleterious effect of cerebral ischemia on DSs morphology and function has been associated with impaired synaptic transmission and neurological deterioration. However, these changes are reversible if cerebral blood flow is restored on time, and this recovery has been associated with neurological improvement following an AIS. Tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) are two serine proteases that, besides catalyzing the conversion of plasminogen into plasmin in the intravascular and pericellular environment, respectively, are also efficient inductors of synaptic plasticity. Accordingly, recent evidence indicates that both, tPA and uPA, protect DSs from the metabolic stress associated with the ischemic injury, and promote their morphological and functional recovery during the recovery phase from an AIS. Here, we will review data indicating that plasticity-induced changes in DSs and the associated post synaptic density play a pivotal role in the recovery process from AIS, making special emphasis on the role of tPA and uPA in this process. PMID- 26846992 TI - Breast Cancer MDA-MB-231 Cells Use Secreted Heat Shock Protein-90alpha (Hsp90alpha) to Survive a Hostile Hypoxic Environment. AB - Rapidly growing tumours in vivo often outgrow their surrounding available blood supply, subjecting themselves to a severely hypoxic microenvironment. Understanding how tumour cells adapt themselves to survive hypoxia may help to develop new treatments of the tumours. Given the limited blood perfusion to the enlarging tumour, whatever factor(s) that allows the tumour cells to survive likely comes from the tumour cells themselves or its associated stromal cells. In this report, we show that HIF-1alpha-overexpressing breast cancer cells, MDA-MB 231, secrete heat shock protein-90alpha (Hsp90alpha) and use it to survive under hypoxia. Depletion of Hsp90alpha secretion from the tumour cells was permissive to cytotoxicity by hypoxia, whereas supplementation of Hsp90alpha-knockout tumour cells with recombinant Hsp90alpha, but not Hsp90beta, protein prevented hypoxia induced cell death via an autocrine mechanism through the LDL receptor-related protein-1 (LRP1) receptor. Finally, direct inhibition of the secreted Hsp90alpha with monoclonal antibody, 1G6-D7, enhanced tumour cell death under hypoxia. Therefore, secreted Hsp90alpha is a novel survival factor for certain tumours under hypoxia. PMID- 26846994 TI - Pollutants and parasites in bycatch teleosts from south eastern Spanish Mediterranean's fisheries: Concerns relating the foodstuff harnessing. AB - This research provides an evaluation of the quality and health status of some locally abundant fish species, usually otter-trawl bycatch species. The study was conducted in the southern and eastern Spanish Mediterranean coast. Mean concentration of heavy metals in muscle and parasitisation indices showed moderate levels. Higher lead concentration was found in fish from the western Alboran and arsenic, cadmium and mercury were more present on fishes from the eastern Alboran area, although most species analysed contain moderate levels of heavy metals in muscle. Concerning parasitisation, F. Anisakidae nematodes were present in all the species, except sardine. Only mercury showed a positive relationship with parasitisation. We also considered three feeding guilds. Metal mean concentrations were higher in benthivores and more littoral fishes. Pelagic planktivores species are the healthiest and the more suitable for consumers from the sanitary point of view. PMID- 26846993 TI - The Development of the General Factor of Psychopathology 'p Factor' Through Childhood and Adolescence. AB - Recent studies have suggested that the structure of psychopathology may be usefully represented in terms of a general factor of psychopathology (p-factor) capturing variance common to a broad range of symptoms transcending diagnostic domains in addition to specific factors capturing variance common to smaller subsets of more closely related symptoms. Little is known about how the general co-morbidity captured by this p-factor develops and whether general co-morbidity increases or decreases over childhood and adolescence. We evaluated two competing hypotheses: 1) dynamic mutualism which predicts growth in general co-morbidity and associated p-factor strength over time and 2) p-differentiation which predicts that manifestations of liabilities towards psychopathology become increasingly specific over time. Data came from the Zurich Project on the Social Development of Children and Youths (z-proso), a longitudinal study of a normative sample (approx. 50 % male) measured at 8 time points from ages 7 to 15. We operationalised general co-morbidity as p-factor strength in a bi-factor model and used omega hierarchical to track how this changed over development. In contrast to the predictions of both dynamic mutualism and p-differentiation, p factor strength remained relatively constant over the studied period suggesting that such processes do not govern the interplay between psychopathological symptoms during this phase of development. Future research should focus on earlier phases of development and on factors that maintain the consistency of symptom-general covariation across this period. PMID- 26846995 TI - Ozonation optimization and modeling for treating diesel-contaminated water. AB - The effect of ozonation on treatment of diesel-contaminated water was investigated on a laboratory scale. Factorial design and response surface methodology (RSM) were used to evaluate and optimize the effects of pH, ozone flow rate, and contact time on the treatment process. A Box-Behnken design was successfully applied for modeling and optimizing the removal of total petroleum hydrocarbons (TPHs). The results showed that ozonation is an efficient technique for removing diesel from aqueous solution. The determination coefficient (R(2)) was found to be 0.9437, indicating that the proposed model was capable of predicting the removal of TPHs by ozonation. The optimum values of experimental initial pH, degree of O3, and reaction time were 7.0, 1.5, and 35 min, respectively, which could contribute to approximately 60% of TPH removal. This result is in good agreement with the predicted value of 57.28%. PMID- 26846996 TI - Relationship between ultrasound elastography and myofibroblast distribution in breast cancer and its clinical significance. AB - The study investigated the relationship between ultrasound elastography (USE) scoring and myofibroblast distribution with expression features of alpha-SMA +/CD34- in patients of Uyghur and Han ethnicities with breast masses in Xinjiang, China. The data was used to evaluate its clinical significance in the early diagnosis of breast cancer. A total of 300 patients with breast masses were included in the study, which involved conventional sonography and USE, with histopathologic diagnosis as the reference standard. Myofibroblast distribution was investigated by detecting the expression levels of alpha-SMA and CD34 in lesions using immunohistochemistry and real-time PCR. Out of 300 lesions, 185 were histologically malignant and 115 benign. The mean elasticity score for malignant lesions was significantly higher than for benign lesions. The expression level of alpha-SMA was elevated while the expression level of CD34 was lower in malignancies, compared with benign lesions. The expression of alpha-SMA was positively associated with the USE scores, while a negative relationship was observed between CD34 expression and USE scoring. The combination of USE and molecular diagnosis provides a promising modality for the early diagnosis and evaluation of the risks in particular types of breast cancer. PMID- 26846997 TI - Addressing future challenges for cancer services: part I. AB - Jane Maher & Gina Radford speak to Gemma Westcott, Commissioning Editor Jane Maher has been Macmillan's Chief Medical Officer since 1999 and now shares the role as Joint Chief Medical Officer with general practitioner Rosie Loftus, reflecting the growing need for specialists and generalists to work more effectively together. She has been a National Health Service (NHS) Improvement Clinical Leader for over 10 years and is a Consultant Clinical Oncologist at Mount Vernon Cancer Centre where she has worked for more than 20 years, during which she helped develop nonsurgical oncology services in five district general hospitals. Jane chaired the Maher Committee for the Department of Health in 1995, led the UK National Audit of Late Effects Pelvic Radiotherapy for the Royal College Of Radiologists (RCR) in 2000 and, most recently, chaired the 'National Cancer Survivorship Initiative, consequences of treatment work stream'. She co founded one of the first Cancer Support and Information services in the UK, winning the Nye Bevan award in 1992 and there are now more than 60 units based on this model. She is a member of the Older People and Cancer Clinical Advisory Group. She has written more than 100 published articles and is a UK representative for cancer survivorship in Europe and advises on Cancer survivorship programs in Denmark and Canada. Gina Radford is Deputy Chief Medical Officer for England, a post she took up in January 2015. Prior to that, she has held a number of roles in public health, at local and regional level. Most recently she was as Centre Director for Anglia and Essex for Public Health England, and as part of that role helped lead nationally on the public health response to Ebola. She was until very recently Chair of one of the NICE public health advisory committees. She has previously worked on a number of national projects, including leading the Department of Health's response to the Shipman Enquiry, undertaking a review of specialist public health for CMO Scotland, chairing a national short life working group looking at the issue of making difficult decisions in NHS Scotland, and undertaking the evaluation of the first pilot (regional bowel cancer detection pilot) for the Be Clear on Cancer National Awareness and Early Diagnosis campaign, on behalf of the Department of Health and Cancer Research UK. Outside work, Gina is a Licensed Lay Minister in the Church of England, and is training to be ordained. She enjoys riding, walking the somewhat aging dog, reading and is the village duck warden! PMID- 26846998 TI - Addressing future challenges for cancer services: part II. AB - Jane Maher & Gina Radford speak to Gemma Westcott, Commissioning Editor Jane Maher has been Macmillan's Chief Medical Officer since 1999 and now shares the role as Joint Chief Medical Officer with general practitioner Rosie Loftus, reflecting the growing need for specialists and generalists to work more effectively together. She has been an National Health Service (NHS) improvement clinical leader for over 10 years and is a Consultant Clinical Oncologist at Mount Vernon Cancer Centre and Hillingdon Hospital where she has worked for more than 20 years, during which she helped develop nonsurgical oncology services in five district general hospitals. She is a senior Clinical Lecturer at University College London and Visiting Professor in Cancer and Supportive Care at the Centre for Complexity Management at the University of Hertfordshire. Jane chaired the Maher Committee for the Department of Health in 1995, led the UK National Audit of Late Effects Pelvic Radiotherapy for the Royal College of Radiologists (RCR) in 2000 and, most recently, chaired the National Cancer Survivorship Initiative Consequences of Treatment work stream. She co-founded one of the first Cancer Support and Information services in the UK, winning the Nye Bevan award in 1992 and there are now more than 60 units based on this model. She is a member of the Older People and Cancer Clinical Advisory Group. She has written more than 100 published articles and is a UK representative for cancer survivorship in Europe and advises on cancer survivorship programs in Denmark and Canada. Gina Radford is Deputy Chief Medical Officer for England, a post she took up in January 2015. Prior to that, she has held a number of roles in public health, at local and regional level. Most recently she was Centre Director for Anglia and Essex for Public Health England, and as a part of that role helped lead nationally on the public health response to Ebola. She was until very recently Chair of one of the NICE public health advisory committees. She has previously worked on a number of national projects, including leading the Department of Health's response to the Shipman Enquiry, undertaking a review of specialist public health for CMO Scotland, chairing a national short life working group looking at the issue of making difficult decisions in NHS Scotland, and undertaking the evaluation of the first pilot (regional bowel cancer detection pilot) for the Be Clear on Cancer National Awareness and Early Diagnosis campaign, on behalf of the Department of Health and Cancer Research UK. Outside work, Gina is a Licensed Lay Minister in the Church of England, and is training to be ordained. She enjoys riding, walking the somewhat aging dog, reading and is the village duck warden! PMID- 26846999 TI - Quantifying the utility of single nucleotide polymorphisms to guide colorectal cancer screening. AB - AIM: To determine whether single nucleotide polymorphisms (SNPs) can be used to identify people who should be screened for colorectal cancer. METHODS: We simulated one million people with and without colorectal cancer based on published SNP allele frequencies and strengths of colorectal cancer association. We estimated 5-year risks of colorectal cancer by number of risk alleles. RESULTS: We identified 45 SNPs with an average 1.14-fold increase colorectal cancer risk per allele (range: 1.05-1.53). The colorectal cancer risk for people in the highest quintile of risk alleles was 1.81-times that for the average person. CONCLUSION: We have quantified the extent to which known susceptibility SNPs can stratify the population into clinically useful colorectal cancer risk categories. PMID- 26847000 TI - Identification and characterization of an anti-oxidative stress-associated mutant of Aspergillus fumigatus transformed by Agrobacterium tumefaciens. AB - Aspergillus fumigatus is one of the most common opportunistic pathogenic fungi, surviving in various environmental conditions. Maintenance of the redox homeostasis of the fungus relies upon the well-organized regulation between reactive oxygen species generated by immune cells or its own organelles, and the activated anti-oxidative stress mechanism. To investigate such a mechanism, the present study obtained a number of randomly-inserted mutants of A. fumigatus, mediated by Agrobacterium tumefaciens. In addition, a high throughput hydrogen peroxide screening system was established to examine ~1,000 mutants. A total of 100 mutants exhibited changes in hydrogen peroxide sensitivity, among which a significant increase in sensitivity was observed in the AFM2658 mutant. Further investigations of the mutant were also performed, in which the sequence of this mutant was characterized using thermal asymmetric interlaced-polymerase chain reaction. This revealed that the insertion site was located on chromosome 2 afu1_92, and the 96 bp sequence was knocked out, which partially comprised a sequence localized between the integral membrane protein coding region and the helix-loop-helix transcription factor coding region. A decrease in the levels of anti-oxidative stress-associated mRNAs were observed, and an increase in reactive oxygen species were detected using fluorescence. The results of the present study demonstrated that this sequence may have a protective role in A. fumigatus in the presence of oxidative stress. PMID- 26847002 TI - Verifying the performance characteristics of the TEG5000 thromboelastogram in the clinical laboratory. AB - OBJECTIVE: To verify the manufacturer performance claims of the TEG5000 with traditional laboratory methods. MATERIALS AND METHODS: Samples were concurrently measured using the TEG5000 analyzer and either PT, APTT, fibrinogen, factor activities, platelet count, or platelet function testing using whole blood or platelet-rich plasma methods. RESULTS: Within-run imprecision yielded coefficient of variation (CV) of <5%. There was no correlation of PT or APTT with R time. Only Factor VIII and factor XII activity significantly correlated with R time. There was significant correlation between k and angle with FBG, PLT count, and factor levels. There was weak inverse correlation between angle results and measures of platelet function. All laboratory methods were significantly correlated with MA. There were significant differences between citrated whole blood and fresh citrated plasma for angle and MA, and between fresh and frozen plasma for R time and MA. We demonstrated a high % inhibition noted with normal, drug naive donors, especially with ADP PLT mapping (50% inhibition), but less so with AA PLT mapping (20% inhibition). For TEG platelet mapping, 19/22 (86.3%) and 17/22 (77.3%) results were concordant with traditional aggregation results. CONCLUSION: We demonstrated both the lack of, and strong correlation between laboratory tests and the TEG parameters. PMID- 26847003 TI - Spatially Resolved Monitoring of Drying of Hierarchical Porous Organic Networks. AB - Evaporation kinetics of water confined in hierarchal polymeric porous media is studied by low field nuclear magnetic resonance (NMR). Systems synthesized with various degrees of cross-linker density render networks with similar pore sizes but different response when soaked with water. Polymeric networks with low percentage of cross-linker can undergo swelling, which affects the porosity as well as the drying kinetics. The drying process is monitored macroscopically by single-sided NMR, with spatial resolution of 100 MUm, while microscopic information is obtained by measurements of spin-spin relaxation times (T2). Transition from a funicular to a pendular regime, where hydraulic connectivity is lost and the capillary flow cannot compensate for the surface evaporation, can be observed from inspection of the water content in different sample layers. Relaxation measurements indicate that even when the larger pore structures are depleted of water, capillary flow occurs through smaller voids. PMID- 26847004 TI - Vector cavity solitons in broad area Vertical-Cavity Surface-Emitting Lasers. AB - We report the experimental observation of two-dimensional vector cavity solitons in a Vertical-Cavity Surface-Emitting Laser (VCSEL) under linearly polarized optical injection when varying optical injection linear polarization direction. The polarization of the cavity soliton is not the one of the optical injection as it acquires a distinct ellipticity. These experimental results are qualitatively reproduced by the spin-flip VCSEL model. Our findings open the road to polarization multiplexing when using cavity solitons in broad-area lasers as pixels in information technology. PMID- 26847005 TI - Validation of the Comprehensive ICF Core Set for Vocational Rehabilitation From the Perspective of Physical Therapists: International Delphi Survey. AB - BACKGROUND: The Comprehensive ICF Core Set for vocational rehabilitation (VR) is a list of essential categories on functioning based on the World Health Organization (WHO) International Classification of Functioning, Disability and Health (ICF), which describes a standard for interdisciplinary assessment, documentation, and communication in VR. OBJECTIVE: The aim of this study was to examine the content validity of the Comprehensive ICF Core Set for VR from the perspective of physical therapists. DESIGN: A 3-round email survey was performed using the Delphi method. METHODS: A convenience sample of international physical therapists working in VR with work experience of >=2 years were asked to identify aspects they consider as relevant when evaluating or treating clients in VR. Responses were linked to the ICF categories and compared with the Comprehensive ICF Core Set for VR. RESULTS: Sixty-two physical therapists from all 6 WHO world regions responded with 3,917 statements that were subsequently linked to 338 ICF categories. Fifteen (17%) of the 90 categories in the Comprehensive ICF Core Set for VR were confirmed by the physical therapists in the sample. Twenty-two additional ICF categories were identified that were not included in the Comprehensive ICF Core Set for VR. LIMITATIONS: Vocational rehabilitation in physical therapy is not well defined in every country and might have resulted in the small sample size. Therefore, the results cannot be generalized to all physical therapists practicing in VR. CONCLUSION: The content validity of the ICF Core Set for VR is insufficient from solely a physical therapist perspective. The results of this study could be used to define a physical therapy-specific set of ICF categories to develop and guide physical therapist clinical practice in VR. PMID- 26847001 TI - The Spermatophore in Glossina morsitans morsitans: Insights into Male Contributions to Reproduction. AB - Male Seminal Fluid Proteins (SFPs) transferred during copulation modulate female reproductive physiology and behavior, impacting sperm storage/use, ovulation, oviposition, and remating receptivity. These capabilities make them ideal targets for developing novel methods of insect disease vector control. Little is known about the nature of SFPs in the viviparous tsetse flies (Diptera: Glossinidae), vectors of Human and Animal African trypanosomiasis. In tsetse, male ejaculate is assembled into a capsule-like spermatophore structure visible post-copulation in the female uterus. We applied high-throughput approaches to uncover the composition of the spermatophore in Glossina morsitans morsitans. We found that both male accessory glands and testes contribute to its formation. The male accessory glands produce a small number of abundant novel proteins with yet unknown functions, in addition to enzyme inhibitors and peptidase regulators. The testes contribute sperm in addition to a diverse array of less abundant proteins associated with binding, oxidoreductase/transferase activities, cytoskeletal and lipid/carbohydrate transporter functions. Proteins encoded by female-biased genes are also found in the spermatophore. About half of the proteins display sequence conservation relative to other Diptera, and low similarity to SFPs from other studied species, possibly reflecting both their fast evolutionary pace and the divergent nature of tsetse's viviparous biology. PMID- 26847006 TI - Preliminary Evaluation of a Modified STarT Back Screening Tool Across Different Musculoskeletal Pain Conditions. AB - BACKGROUND: The STarT Back Screening Tool is a validated multidimensional screening measure and risk stratification tool for people with low back pain. OBJECTIVE: The study objective was to compare relationships between a modified STarT Back Screening Tool (mSBT) and clinical and psychological measures in people with low back, neck, shoulder, and knee pain. The hypothesis was that the relationships between mSBT scores and clinical and psychological measure scores would be similar across the included musculoskeletal pain conditions. DESIGN: A cross-sectional, secondary analysis was done in this study. METHODS: Participants with low back (n=118), neck (n=92), shoulder (n=106), or knee (n=111) pain were recruited, and an mSBT was developed for use across the pain conditions. Separate hierarchical linear regression models were developed, with clinical (health status, pain intensity, and disability) and psychological (kinesiophobia, catastrophizing, fear avoidance, anxiety, depressive symptoms, and self-efficacy) measures as dependent variables. Demographic and pain region variables were entered in the first step, mSBT scores were entered in the second step, and pain region * mSBT interactions were entered in the last step. RESULTS: In the final models, no interactions were identified, suggesting that dependent measure scores did not differ by pain region. The strongest contributor for all dependent variables was mSBT scores (beta=|0.32|-|0.68|); higher mSBT scores were associated with poorer health status and self-efficacy and with higher levels of pain intensity, disability, kinesiophobia, catastrophizing, fear avoidance, anxiety, and depressive symptoms. LIMITATIONS: Generalizability was restricted to physical therapy outpatients with the included pain conditions. The mSBT used in this study is not ready for clinical implementation. CONCLUSIONS: The results of this study support the feasibility of using a single measure for concise risk assessment across different musculoskeletal pain conditions. Further longitudinal studies are needed to better direct the clinical use of an mSBT in people with low back, neck, shoulder, and knee pain. PMID- 26847007 TI - "Crawling Out of the Cocoon": Patients' Experiences of a Physical Therapy Exercise Intervention in the Treatment of Major Depression. AB - BACKGROUND: Although the effectiveness of physical exercise for depression has been studied for many years, few studies have described patients' experiences of what exercise means to them, beyond the biological focus. Moreover, exercise as a treatment for depression is rarely explored in a physical therapy context. OBJECTIVES: The purpose of this study was to explore a physical therapy exercise intervention, as experienced by people with major depression. DESIGN: This study had an inductive approach and used qualitative content analysis. METHODS: Semistructured interviews were conducted with 13 people who participated in physical therapist-guided aerobic exercise in a randomized controlled trial. All participants were diagnosed with major depression according to the Diagnostic and Statistical Manual of Mental Disorders. Data were collected and analyzed in an inductive manner using qualitative content analysis according to Graneheim and Lundman. RESULTS: Four categories emerged: (1) struggling toward a healthy self, (2) challenging the resistance, (3) feeling alive but not euphoric, and (4) needing someone to be there for you. The participants experienced that although the exercise intervention was hard work, it enhanced the feeling of being alive and made them feel that they were doing something good for themselves. These feelings were a welcome contrast to the numbness and stagnation they experienced during depression. LIMITATIONS: The study was conducted in Swedish primary care. Transferability of results must be viewed in relation to context. CONCLUSIONS: Exercise in a physical therapy context can improve the patients' perception of their physical ability and create a sense of liveliness, improving their depressed state. The therapeutic relationship is essential for supporting the patient's vulnerability and ambiguity in an empathic and perceptive way. PMID- 26847009 TI - Prevalence of Wheelchair and Scooter Use Among Community-Dwelling Canadians. AB - BACKGROUND: Mobility impairments are the third leading cause of disability for community-dwelling Canadians. Wheelchairs and scooters help compensate for these challenges. There are limited data within the last decade estimating the prevalence of wheelchair and scooter use in Canada. OBJECTIVE: The aims of this study were: (1) to estimate the prevalence of wheelchair and scooter use in Canada and (2) to explore relevant demographic characteristics of wheelchair and scooter users. DESIGN: This study was a secondary analysis of a cross-sectional national survey. METHODS: The Canadian Survey on Disability (2012) collected data on wheelchair and scooter use from community-dwelling individuals aged 15 years and over with a self-identified activity limitation on the National Household Survey. Prevalence estimates were calculated as weighted frequencies, with cross tabulations to determine the number of wheelchair and scooter users in Canada, by province, and demographic characteristics (ie, age, sex) and bootstrapping to estimate the variance of all point estimates. RESULTS: There were approximately 288,800 community-dwelling wheelchair and scooter users aged 15 years and over, representing 1.0% of the Canadian population. The sample included 197,560 manual wheelchair users, 42,360 powered wheelchair users, and 108,550 scooter users. Wheelchair and scooter users were predominantly women, with a mean age of 65 years. Approximately 50,620 individuals used a combination of 2 different types of devices. LIMITATIONS: The results are representative of individuals living in the community in Canada and exclude individuals in residential or group-based settings; estimates do not represent the true population prevalence. CONCLUSION: This analysis is the first in more than 10 years to provide a prevalence estimate and description of wheelchair and scooter users in Canada. Since 2004, there has been an increase in the proportion of the population who use wheelchairs and scooters, likely related to an aging Canadian population. These new prevalence data have potential to inform policy, research, and clinical practice. PMID- 26847010 TI - Test-Retest Reliability of Dual-Task Outcome Measures in People With Parkinson Disease. AB - BACKGROUND: Dual-task (DT) training is gaining ground as a physical therapy intervention in people with Parkinson disease (PD). Future studies evaluating the effect of such interventions need reliable outcome measures. To date, the test retest reliability of DT measures in patients with PD remains largely unknown. OBJECTIVE: The purpose of this study was to assess the reliability of DT outcome measures in patients with PD. DESIGN: A repeated-measures design was used. METHODS: Patients with PD ("on" medication, Mini-Mental State Examination score >=24) performed 2 cognitive tasks (ie, backward digit span task and auditory Stroop task) and 1 functional task (ie, mobile phone task) in combination with walking. Tasks were assessed at 2 time points (same hour) with an interval of 6 weeks. Test-retest reliability was assessed for gait while performing each secondary task (DT gait) for both cognitive tasks while walking (DT cognitive) and for the functional task while walking (DT functional). RESULTS: Sixty-two patients with PD (age=39-89 years, Hoehn and Yahr stages II-III) were included in the study. Intraclass correlation coefficients (ICCs) showed excellent reliability for DT gait measures, ranging between .86 and .95 when combined with the digit span task, between .86 and .95 when combined with the auditory Stroop task, and between .72 and .90 when combined with the mobile phone task. The standard error of measurements for DT gait speed varied between 0.06 and 0.08 m/s, leading to minimal detectable changes between 0.16 and 0.22 m/s. With regard to DT cognitive measures, reaction times showed good-to-excellent reliability (digit span task: ICC=.75; auditory Stroop task: ICC=.82). LIMITATIONS: The results cannot be generalized to patients with advanced disease or to other DT measures. CONCLUSIONS: In people with PD, DT measures proved to be reliable for use in clinical studies and look promising for use in clinical practice to assess improvements after DT training. Large effects, however, are needed to obtain meaningful effect sizes. PMID- 26847008 TI - Developmental Biology and Regenerative Medicine: Addressing the Vexing Problem of Persistent Muscle Atrophy in the Chronically Torn Human Rotator Cuff. AB - Persistent muscle atrophy in the chronically torn rotator cuff is a significant obstacle for treatment and recovery. Large atrophic changes are predictive of poor surgical and nonsurgical outcomes and frequently fail to resolve even following functional restoration of loading and rehabilitation. New insights into the processes of muscle atrophy and recovery gained through studies in developmental biology combined with the novel tools and strategies emerging in regenerative medicine provide new avenues to combat the vexing problem of muscle atrophy in the rotator cuff. Moving these treatment strategies forward likely will involve the combination of surgery, biologic/cellular agents, and physical interventions, as increasing experimental evidence points to the beneficial interaction between biologic therapies and physiologic stresses. Thus, the physical therapy profession is poised to play a significant role in defining the success of these combinatorial therapies. This perspective article will provide an overview of the developmental biology and regenerative medicine strategies currently under investigation to combat muscle atrophy and how they may integrate into the current and future practice of physical therapy. PMID- 26847011 TI - Adding Psychosocial Factors Does Not Improve Predictive Models for People With Spinal Pain Enough to Warrant Extensive Screening for Them at Baseline. AB - BACKGROUND: Chiropractors throughout the world by and large focus on patients with musculoskeletal complaints who are generally in good health. Currently, it is widely accepted that neck pain and low back pain are best understood as biopsychosocial phenomena. OBJECTIVE: The purpose of this study was to determine whether certain psychosocial factors provide added value for predicting recovery. DESIGN: This was a prospective, multicenter, chiropractic, practice-based cohort study in Belgium and the Netherlands. METHODS: A total of 917 participants, 326 with neck pain and 591 with low back pain, completed self-administered questionnaires at baseline and at 3, 6, and 12 months. They provided information on several demographic, biomedical, and psychosocial variables. Lasting perceived recovery was used as the outcome measure, that is, recovery at all follow-up assessments from 3 months on. Twenty-seven potential predictors of outcome were used to build the predictive model. Stepwise, backward generalized estimating equation regression models were used to take into account the clustering of participants within practices. For assessment of the added value of psychosocial variables, 2 model fit indexes were compared. RESULTS: After the addition of psychosocial variables, predictors in the final model for neck pain included occupational status, body mass index, duration of complaints, previous treatment, and participant expectations (the model fit was marginally improved from 0.684 to 0.695 for the area under the curve and from 65.0% to 66.1% for the percentage correctly predicted). In the final model for low back pain, the selected predictors included country of treatment, age, duration of complaints, previous imaging, and somatization (the area under the curve changed from 0.669 to 0.715, and the percentage correctly predicted changed from 68.6% to 69.5%). Only a minority of participants had high scores on psychological variables. LIMITATIONS: The reliability and validity of lasting recovery as an outcome measure have not been tested. The cohort needs to be seen as a convenience sample. Selection bias, therefore, not be ruled out. There are no indications, however, that patients with complex psychosocial profiles were excluded from this study. CONCLUSIONS: Psychosocial variables provided little added value for predicting outcome in people who had neck pain or low back pain and sought chiropractic care. Therefore, chiropractors should not screen extensively for them at baseline. With regard to the identification of the small subgroup of people with high scores on psychosocial variables and a high risk for chronic pain, further investigation is needed. PMID- 26847012 TI - Critical and Theoretical Perspective on Scapular Stabilization: What Does It Really Mean, and Are We on the Right Track? AB - Stabilization exercises have been a focus and mainstay of many therapeutic and performance training programs in the past decade. Whether the focus is core stabilization for the spine or scapular stabilization, clinicians and trainers alike have endorsed these programs, largely on the basis of conceptual theory and anecdotal experience. The notion that an unstable scapula is related to shoulder dysfunction and pathology is well accepted, but is it accurate? The aim of this perspective article is to challenge the concept of scapular stabilization through the application of biomechanical and motor control constructs. The objectives are to critically examine current beliefs about scapular stabilization, to discuss definitions of stabilization and stability in the context of the scapulothoracic region, and to evaluate key evidence regarding scapular stabilization and scapular dyskinesia. Several new approaches that may affect the understanding of normal and atypical scapula motion are explored. Finally, a historical analogy is presented and future research and clinical directions are suggested. The aims are to lead readers to the essential concepts implied on scapular stabilization, to increase the critical thought process in rehabilitation practice, and to suggest some open topics to be explored in future research. PMID- 26847013 TI - Limitations in the Activity of Mobility at Age 6 Years After Difficult Birth at Term: Prospective Cohort Study. AB - BACKGROUND: A difficult birth at term (DBAT) may manifest as fetal acidosis and low Apgar scores and is often referred to as "perinatal asphyxia," especially when infants show signs of neonatal encephalopathy (NE). In contrast to DBAT resulting in moderate-to-severe NE, which is associated with neurodevelopmental disorders, little is known about the prognosis of less severe forms of DBAT, with or without NE. OBJECTIVE: The purpose of this study was to evaluate the International Classification of Functioning, Disability and Health, Children & Youth Version activity "mobility" and other neurodevelopmental sequelae in infants with DBAT at age 6 years. METHODS: The index cohort (n=62; 35 boys, 27 girls) consisted of consecutive term infants with DBAT based on clinical criteria in a Dutch nonacademic hospital from 1999 to 2005. Neonatal encephalopathy was assessed according to the Sarnat grading system and excluded infants with severe NE. The matched reference cohort (n=81; 49 boys, 32 girls) consisted of healthy term infants. The primary outcome at 6 years was limited mobility (Movement Assessment Battery for Children score <=15th percentile). Secondary outcomes included learning and behavioral problems and the presence of minor neurological dysfunction. RESULTS: Three children developed cerebral palsy and were excluded from analyses. Children with DBAT more often had limited mobility than children without DBAT (risk ratio [RR]=2.44; 95% confidence interval [95% CI]=1.16, 5.14). The risk of limited mobility rose with increasing severity of NE (mild NE: RR=3.38; 95% CI=1.40, 8.16; moderate NE: RR=4.00; 95% CI=1.54, 10.40), and manual abilities especially were affected (RR=4.12; 95% CI=1.40, 12.14). Learning problems, need for physical therapy, and complex minor neurological dysfunction were more common in children with DBAT than in children without DBAT. CONCLUSIONS: Term infants who develop mild or moderate NE following DBAT are at increased risk for limited mobility at age 6 years. Routine monitoring of neuromotor development in these children is warranted. PMID- 26847014 TI - Cervico-ocular Reflex Is Increased in People With Nonspecific Neck Pain. AB - BACKGROUND: Neck pain is a widespread complaint. People experiencing neck pain often present an altered timing in contraction of cervical muscles. This altered afferent information elicits the cervico-ocular reflex (COR), which stabilizes the eye in response to trunk-to-head movements. The vestibulo-ocular reflex (VOR) elicited by the vestibulum is thought to be unaffected by afferent information from the cervical spine. OBJECTIVE: The aim of the study was to measure the COR and VOR in people with nonspecific neck pain. DESIGN: This study utilized a cross sectional design in accordance with the STROBE statement. METHODS: An infrared eye-tracking device was used to record the COR and the VOR while the participant was sitting on a rotating chair in darkness. Eye velocity was calculated by taking the derivative of the horizontal eye position. Parametric statistics were performed. RESULTS: The mean COR gain in the control group (n=30) was 0.26 (SD=0.15) compared with 0.38 (SD=0.16) in the nonspecific neck pain group (n=37). Analyses of covariance were performed to analyze differences in COR and VOR gains, with age and sex as covariates. Analyses of covariance showed a significantly increased COR in participants with neck pain. The VOR between the control group, with a mean VOR of 0.67 (SD=0.17), and the nonspecific neck pain group, with a mean VOR of 0.66 (SD=0.22), was not significantly different. LIMITATIONS: Measuring eye movements while the participant is sitting on a rotating chair in complete darkness is technically complicated. CONCLUSIONS: This study suggests that people with nonspecific neck pain have an increased COR. The COR is an objective, nonvoluntary eye reflex and an unaltered VOR. This study shows that an increased COR is not restricted to patients with traumatic neck pain. PMID- 26847015 TI - Neural Stem Cell Therapy and Rehabilitation in the Central Nervous System: Emerging Partnerships. AB - The goal of regenerative medicine is to restore function through therapy at levels such as the gene, cell, tissue, or organ. For many disorders, however, regenerative medicine approaches in isolation may not be optimally effective. Rehabilitation is a promising adjunct therapy given the beneficial impact that physical activity and other training modalities can offer. Accordingly, "regenerative rehabilitation" is an emerging concentration of study, with the specific goal of improving positive functional outcomes by enhancing tissue restoration following injury. This article focuses on one emerging example of regenerative rehabilitation-namely, the integration of clinically based protocols with stem cell technologies following central nervous system injury. For the purposes of this review, the state of stem cell technologies for the central nervous system is summarized, and a rationale for a synergistic benefit of carefully orchestrated rehabilitation protocols in conjunction with cellular therapies is provided. An overview of practical steps to increase the involvement of physical therapy in regenerative rehabilitation research also is provided. PMID- 26847016 TI - Home dim light melatonin onsets with measures of compliance in delayed sleep phase disorder. AB - The dim light melatonin onset (DLMO) assists with the diagnosis and treatment of circadian rhythm sleep disorders. Home DLMOs are attractive for cost savings and convenience, but can be confounded by home lighting and sample timing errors. We developed a home saliva collection kit with objective measures of light exposure and sample timing. We report on our first test of the kit in a clinical population. Thirty-two participants with delayed sleep phase disorder (DSPD; 17 women, aged 18-52 years) participated in two back-to-back home and laboratory phase assessments. Most participants (66%) received at least one 30-s epoch of light >50 lux during the home phase assessments, but for only 1.5% of the time. Most participants (56%) collected every saliva sample within 5 min of the scheduled time. Eighty-three per cent of home DLMOs were not affected by light or sampling errors. The home DLMOs occurred, on average, 10.2 min before the laboratory DLMOs, and were correlated highly with the laboratory DLMOs (r = 0.93, P < 0.001). These results indicate that home saliva sampling with objective measures of light exposure and sample timing, can assist in identifying accurate home DLMOs. PMID- 26847017 TI - Relevance of workplace social mixing during influenza pandemics: an experimental modelling study of workplace cultures. AB - Workplaces are one of the most important regular meeting places in society. The aim of this study was to use simulation experiments to examine the impact of different workplace cultures on influenza dissemination during pandemics. The impact is investigated by experiments with defined social-mixing patterns at workplaces using semi-virtual models based on authentic sociodemographic and geographical data from a North European community (population 136 000). A simulated pandemic outbreak was found to affect 33% of the total population in the community with the reference academic-creative workplace culture; virus transmission at the workplace accounted for 10.6% of the cases. A model with a prevailing industrial-administrative workplace culture generated 11% lower incidence than the reference model, while the model with a self-employed workplace culture (also corresponding to a hypothetical scenario with all workplaces closed) produced 20% fewer cases. The model representing an academic creative workplace culture with restricted workplace interaction generated 12% lower cumulative incidence compared to the reference model. The results display important theoretical associations between workplace social-mixing cultures and community-level incidence rates during influenza pandemics. Social interaction patterns at workplaces should be taken into consideration when analysing virus transmission patterns during influenza pandemics. PMID- 26847018 TI - GRHL2 genetic polymorphisms may confer a protective effect against sudden sensorineural hearing loss. AB - Genetic polymorphisms in grainyhead-like 2 (GRHL2) variants were examined for their suspected association with sudden sensorineural hearing loss (SSHL). Between January 2009 and April 2014, 190 patients with SSHL, who were diagnosed at the Departments of Otorhinolaryngology Head and Neck Surgery at Kaihua People's Hospital and Hangzhou First People's Hospital, were selected for the present study and defined as the SSHL group. A group of 210 healthy individuals were defined as the control group. Polymerase chain reaction (PCR)-restriction fragment length polymorphism was used to detect GRHL2 genotypes, using genomic DNA isolated from peripheral blood as PCR templates. GRHL2 rs611419 genetic polymorphisms conferred a protective effect against SSHL (AT+TT vs. AA: OR=0.63, 95% CI=0.41-0.98, P=0.038). In addition, rs10955255 polymorphisms were associated with a reduced risk of SSHL (AA vs. GG: OR=0.54, 95% CI=0.31-0.95, P=0.032; GA+AA vs. GG: OR=0.58, 95% CI=0.38-0.89, P=0.012). Combined genotypes of rs611419, rs10955255 and rs6989650 in the GRHL2 gene are also associated with a reduced risk of SSHL (P=0.035). In subjects who consumed alcohol, co-occurrence of 3-8 variant alleles conferred increased resistance to SSHL, compared with the occurrence of 0-2 variant alleles (OR=0.40, 95% CI=0.21-0.76, P=0.004). GRHL2 genetic polymorphisms, rs611419 and rs10955255, have a protective role against SSHL and reduce the risk of SSHL. However, rs6989650 is not associated with SSHL. PMID- 26847019 TI - The significance of anterolateral neck cysts in early diagnosis of fetal malformations. AB - OBJECTIVE: The objective of this study is to examine the association of lateral fetal neck cysts with increased nuchal translucency, chromosomal abnormalities and fetal malformations. METHOD: In a consecutive collective of 4216 prenatal ultrasound examinations between 11 and 17 weeks of gestation 32 fetuses with lateral neck cysts were found. The size of the cysts was examined. The association of the findings with increased nuchal translucency, chromosomal aberrations and fetal malformations was examined. RESULTS: All but two out of 32 cases had bilateral cysts. Seventeen fetuses had aneuploidy and an increased nuchal translucency, 15 of those with major structural malformations. Of the 15 fetuses with normal karyotype nine (60%) had an increased nuchal translucency, seven had a fetal malformation or hydrops. A favorable outcome was found in 6/15 fetuses with normal karyotype and normal nuchal translucency. Lateral neck cyst diameter was associated to nuchal translucency, chromosomal abnormality and/or fetal malformations. Cysts smaller than 3 mm had a favorable outcome even in the presence of an increased nuchal translucency. CONCLUSION: Fetuses with lateral neck cysts often not only present with increased nuchal translucency and chromosomal aberrations but also with fetal malformations. Fetuses with lateral neck cysts and increased nuchal translucency were aneuploid or had a fetal malformation in 85%. Cysts smaller than 3 mm had a favorable outcome. (c) 2016 John Wiley & Sons, Ltd. PMID- 26847020 TI - Risk factors for bleeding after liver biopsy. AB - OBJECTIVE: Determine factors that increase the risk of bleeding after liver biopsy. METHODS: Retrospective review of radiology and clinical databases from Jan 2008 to Jun 2014 revealed 847 patients with liver biopsy. Of these, 154 (group I) had targeted biopsy of focal lesion and 142 (group 2) had random core biopsy for diffuse liver disease. The rest of the patients were excluded due to insufficient post-biopsy data. Data including pre-biopsy laboratory results, history of transfusion, and biopsy complications were recorded in the study cohort. After review of initial results, a "Risk Score" for bleeding was created using platelet count, INR, estimated glomerular filtration rate (eGFR), and suspicion of malignancy. Zero point was given for normal laboratory results or absence of malignancy. One point was given for mildly abnormal laboratory values or presence of malignancy. Severe biochemical abnormalities, e.g., INR > 2.0, eGFR < 30 mL/min, or platelet count <= 50 * 10(9)/L were given two points each. The "Risk Score" was made of adding individual points. RESULTS: Of 847 patients queried by retrospective database search, 296 had adequate records for the period of 2 weeks prior to biopsy to 4 weeks after biopsy. The remaining patients had liver biopsy as outpatients and probably did not have bleeding complications but no electronic records were found to confirm this. 25 (8.4%) of 296 patients had post-biopsy bleeding, with incidences of 11.7% and 4.9% in groups 1 and 2 (p = 0.04). On logistic regression analysis, the only significant predictor of bleeding was the "Risk Score" (p = 0.01, odds ratio 4.6). There was substantial overlap in INR, and platelet count in bleeders vs. non-bleeders. Pre-biopsy fresh frozen plasma or platelet concentrate infusions did not reduce the risk of bleeding. CONCLUSION: INR and platelet count are not an independent risk factors for post-biopsy bleeding. A "Risk Score" made up of individual risk factors was a better predictor of bleeding. PMID- 26847021 TI - The diffusion-weighted imaging of renal leiomyoma. PMID- 26847022 TI - Imaging spectrum of cholangiocarcinoma: role in diagnosis, staging, and posttreatment evaluation. AB - Cholangiocarcinoma, a tumor of biliary epithelium, is increasing in incidence. The imaging appearance, behavior, and treatment of cholangiocarcinoma differ according to its location and morphology. Cholangiocarcinoma is usually classified as intrahepatic, perihilar, or distal. The three morphologies are mass forming, periductal sclerosing, and intraductal growing. As surgical resection is the only cure, prompt diagnosis and accurate staging is crucial. In staging, vascular involvement, longitudinal spread, and lymphadenopathy are important to assess. The role of liver transplantation for unresectable peripheral cholangiocarcinoma will be discussed. Locoregional therapy can extend survival for those with unresectable intrahepatic tumors. The main risk factors predisposing to cholangiocarcinoma are parasitic infections, primary sclerosing cholangitis, choledochal cysts, and viral hepatitis. Several inflammatory conditions can mimic cholangiocarcinoma, including IgG4 disease, sclerosing cholangitis, Mirizzi's syndrome, and recurrent pyogenic cholangitis. The role of PET in diagnosis and staging will also be discussed. Radiologists play a crucial role in diagnosis, staging, and treatment of this disease. PMID- 26847023 TI - Role of PET CT scan in redefining treatment of incidental gall bladder carcinoma. AB - INTRODUCTION: Incidental diagnosis of gall bladder cancer is increasing. The role of PET-CT in modifying the extent of surgery and adjuvant treatment is still unclear. We have evaluated the same in this study. METHODS: This is a prospective audit of gall bladder cancer from Tata Memorial Hospital, Mumbai, India. Patients found non-metastatic on initial imaging underwent laparotomy for revision surgery. RESULTS: One hundred and eight patients had a PET-CT scan done before revision surgery. Median duration of PET-CT from primary surgery was 42 days. PET scan of 64 (59.3%) patients had no uptake in body (N-PET). Rest had loco-regional uptake (L-PET). N-PET patients had lesser residual disease than L-PET patients (23% vs. 52%; P = 0.004). N-PET pT1b patients had no residual disease as compared to L-PET patients (0% vs. 33%, P = 0.028). pT1b patients did not have residual disease in liver wedge irrespective of PET status. Majority of the recurrences were distant and happened in pT2 patients. RFS was longer in N-PET than L-PET patients (P = 0.09) and in pT1b patients than pT2 and pT3 (P = 0.006). OS was longer in pT1b patients than pT2 patients (P = 0.038). CONCLUSIONS: PET-CT scan is useful to stratify patients with incidentally diagnosed gall bladder cancer for effective treatment. Liver wedge resection may be avoided in all pT1b patients. PET negative pT1b patients may be observed as chance of relapse is low. There may be a role for giving chemotherapy to all pT2 patients as they have high chance of recurrence and nodal metastases. J. Surg. Oncol. 2016;113:652-658. (c) 2016 Wiley Periodicals, Inc. PMID- 26847024 TI - Predictors of early death and survival among children, adolescents and young adults with acute myeloid leukaemia in California, 1988-2011: a population-based study. AB - A better understanding of factors associated with early death and survival among children, adolescents and young adults with acute myeloid leukaemia (AML) may guide health policy aimed at improving outcomes in these patients. We examined trends in early death and survival among 3935 patients aged 0-39 years with de novo AML in California during 1988-2011 and investigated the associations between sociodemographic and selected clinical factors and outcomes. Early death declined from 9.7% in 1988-1995 to 7.1% in 2004-2011 (P = 0.062), and survival improved substantially over time. However, 5-year survival was still only 50% (95% confidence interval 47-53%) even in the most recent treatment period (2004-2011). Overall, the main factors associated with poor outcomes were older age at diagnosis, treatment at hospitals not affiliated with National Cancer Institute designated cancer centres, and black race/ethnicity. For patients diagnosed during 1996-2011, survival was lower among those who lacked health insurance compared to those with public or private insurance. We conclude that mortality after AML remained strikingly high in California and increased with age. Possible strategies to improve outcomes include wider insurance coverage and treatment at specialized cancer centres. PMID- 26847025 TI - A novel comparative pattern count analysis reveals a chronic ethanol-induced dynamic shift in immediate early NF-kappaB genome-wide promoter binding during liver regeneration. AB - Liver regeneration after partial hepatectomy is a clinically important process that is impaired by adaptation to chronic alcohol intake. We focused on the initial time points following partial hepatectomy (PHx) to analyze the genome wide binding activity of NF-kappaB, a key immediate early regulator. We investigated the effect of chronic alcohol intake on immediate early NF-kappaB genome-wide localization, in the adapted state as well as in response to partial hepatectomy, using chromatin immunoprecipitation followed by promoter microarray analysis. We found many ethanol-specific NF-kappaB binding target promoters in the ethanol-adapted state, corresponding to the regulation of biosynthetic processes, oxidation-reduction and apoptosis. Partial hepatectomy induced a diet independent shift in NF-kappaB binding loci relative to the transcription start sites. We employed a novel pattern count analysis to exhaustively enumerate and compare the number of promoters corresponding to the temporal binding patterns in ethanol and pair-fed control groups. The highest pattern count corresponded to promoters with NF-kappaB binding exclusively in the ethanol group at 1 h post PHx. This set was associated with the regulation of cell death, response to oxidative stress, histone modification, mitochondrial function, and metabolic processes. Integration with the global gene expression profiles to identify putative transcriptional consequences of NF-kappaB binding patterns revealed that several of ethanol-specific 1 h binding targets showed ethanol-specific differential expression through 6 h post PHx. Motif analysis yielded co-incident binding loci for STAT3, AP-1, CREB, C/EBP-beta, PPAR-gamma and C/EBP-alpha, likely participating in co-regulatory modules with NF-kappaB in shaping the immediate early response to PHx. We conclude that adaptation to chronic ethanol intake disrupts the NF-kappaB promoter binding landscape with consequences for the immediate early gene regulatory response to the acute challenge of PHx. PMID- 26847026 TI - GFI1 as a novel prognostic and therapeutic factor for AML/MDS. AB - Genetic and epigenetic aberrations contribute to the initiation and progression of acute myeloid leukemia (AML). GFI1, a zinc-finger transcriptional repressor, exerts its function by recruiting histone deacetylases to target genes. We present data that low expression of GFI1 is associated with an inferior prognosis of AML patients. To elucidate the mechanism behind this, we generated a humanized mouse strain with reduced GFI1 expression (GFI1-KD). Here we show that AML development induced by onco-fusion proteins such as MLL-AF9 or NUP98-HOXD13 is accelerated in mice with low human GFI1 expression. Leukemic cells from animals that express low levels of GFI1 show increased H3K9 acetylation compared to leukemic cells from mice with normal human GFI1 expression, resulting in the upregulation of genes involved in leukemogenesis. We investigated a new epigenetic therapy approach for this subgroup of AML patients. We could show that AML blasts from GFI1-KD mice and from AML patients with low GFI1 levels were more sensitive to treatment with histone acetyltransferase inhibitors than cells with normal GFI1 expression levels. We suggest therefore that GFI1 has a dose dependent role in AML progression and development. GFI1 levels are involved in epigenetic regulation, which could open new therapeutic approaches for AML patients. PMID- 26847030 TI - 'Accentuate the positive': Taking advice from a 1940s song. PMID- 26847027 TI - Pre-BCR signaling in precursor B-cell acute lymphoblastic leukemia regulates PI3K/AKT, FOXO1 and MYC, and can be targeted by SYK inhibition. AB - Precursor-B-cell receptor (pre-BCR) signaling and spleen tyrosine kinase (SYK) recently were introduced as therapeutic targets for patients with B-cell acute lymphoblastic leukemia (B-ALL), but the importance of this pathway in B-ALL subsets and mechanism of downstream signaling have not fully been elucidated. Here, we provide new detailed insight into the mechanism of pre-BCR signaling in B-ALL. We compared the effects of pharmacological and genetic disruption of pre BCR signaling in vitro and in mouse models for B-ALL, demonstrating exquisite dependency of pre-BCR(+) B-ALL, but not other B-ALL subsets, on this signaling pathway. We demonstrate that SYK, PI3K/AKT, FOXO1 and MYC are important downstream mediators of pre-BCR signaling in B-ALL. Furthermore, we define a characteristic immune phenotype and gene expression signature of pre-BCR(+) ALL to distinguish them from other B-ALL subsets. These data provide comprehensive new insight into pre-BCR signaling in B-ALL and corroborate pre-BCR signaling and SYK as promising new therapeutic targets in pre-BCR(+) B-ALL. PMID- 26847028 TI - Longitudinal copy number, whole exome and targeted deep sequencing of 'good risk' IGHV-mutated CLL patients with progressive disease. AB - The biological features of IGHV-M chronic lymphocytic leukemia responsible for disease progression are still poorly understood. We undertook a longitudinal study close to diagnosis, pre-treatment and post relapse in 13 patients presenting with cMBL or Stage A disease and good-risk biomarkers (IGHV-M genes, no del(17p) or del(11q) and low CD38 expression) who nevertheless developed progressive disease, of whom 10 have required therapy. Using cytogenetics, fluorescence in situ hybridisation, genome-wide DNA methylation and copy number analysis together with whole exome, targeted deep- and Sanger sequencing at diagnosis, we identified mutations in established chronic lymphocytic leukemia driver genes in nine patients (69%), non-coding mutations (PAX5 enhancer region) in three patients and genomic complexity in two patients. Branching evolutionary trajectories predominated (n=9/13), revealing intra-tumoural epi- and genetic heterogeneity and sub-clonal competition before therapy. Of the patients subsequently requiring treatment, two had sub-clonal TP53 mutations that would not be detected by standard methodologies, three qualified for the very-low-risk category defined by integrated mutational and cytogenetic analysis and yet had established or putative driver mutations and one patient developed progressive, therapy-refractory disease associated with the emergence of an IGHV-U clone. These data suggest that extended genomic and immunogenetic screening may have clinical utility in patients with apparent good-risk disease. PMID- 26847031 TI - The impact of self-transcendence on physical health status promotion in multiple sclerosis patients attending peer support groups. AB - This study aimed to investigate the effect of self-transcendence on the physical health of multiple sclerosis (MS) patients attending peer support groups. This study was a quasi-experimental before-and-after design including 33 MS patients in three groups: 10 men in the men-only group, 11 women in the women-only group, and 12 men and women in the mixed group. Participants were required to attend eight weekly sessions of 2 h each. Instruments included the physical health section of the Multiple Sclerosis Quality of Life Inventory and Reed's Self Transcendence Scale. Peer support group attendance was found to have a significant positive effect on the physical health and self-transcendence of MS patients when comparing average scores before and after attendance. Regression analysis showed that improvement in self-transcendence predicted improvement in physical health. Results show the positive effects of peer support groups on self transcendence and physical health in MS patients, and suggest that improvement in well-being can be gained by promoting self-transcendence and physical health. PMID- 26847032 TI - Muslims and Medical Ethics: Time to Move Forward by Going Back. PMID- 26847033 TI - Clinical characteristics of patients having single versus multiple patient encounters within a palliative care programme. AB - OBJECTIVE: The objective of this study was to describe the clinical characteristics of patient initial presentations, and to explore associations between patients' clinical characteristics at initial presentation and number of encounters (single vs multiple) to an integrated palliative care programme. METHODS: This was a retrospective study of a decedent cohort of 2922 patient initial presentations to the Edmonton Zone Palliative Care Program (EZPCP). Data included age, gender, setting of encounter, diagnosis, Edmonton Symptom Assessment System, CAGE, Mini-Mental Status Examination, Palliative Performance Status, Edmonton Classification System for Cancer Pain and time to death. RESULTS: On initial presentation to the EZPCP, the mean age was 73 (SD 14 years), with 1358 (46%) being female, and the majority having a cancer diagnosis (n=2376, 81%), the most common of which was gastrointestinal primary (n=681, 29%). In univariate analyses, patients with younger age (<60), higher palliative performance status (>40%), a malignant diagnosis, gastrointestinal primary or unimpaired cognition at initial presentation were significantly associated with multiple encounters with an integrated palliative care programme (p<0.05). In a multivariate regression analysis, a malignant diagnosis, longer survival, higher performance status and initial entry through acute care sites were independently associated with multiple encounters in the programme (p<0.001). CONCLUSIONS: Larger prospective studies are warranted to further elucidate the complex relationships between patient clinical characteristics, initial presentations and subsequent encounters to an integrated palliative care programme. PMID- 26847034 TI - The death of patients with terminal cancer: the distress experienced by their children and medical professionals who provide the children with support care. AB - BACKGROUND: Few studies have been conducted on the experiences of children of terminally ill patients or hospital-based medical professionals supporting such children. AIM: This study explored distress among individuals whose parents died of cancer in childhood and among hospital-based medical professionals supporting such children. DESIGN: A qualitative study. SETTING/PARTICIPANTS: The sample was 12 adults whose parents had died of cancer in childhood and 20 hospital-based medical professionals supporting children of patients' with terminal cancer. In depth interviews were conducted, focusing on the distress experienced by the participants. The data were analysed thematically. RESULTS: Among adults whose parents died of cancer in childhood, we identified themes related to the period before death (eg, concealing the parent's illness), the time of death (eg, alienation due to isolation from the parent), soon after death (eg, fear and shock evoked by the bizarre circumstances, regrets regarding the relationship with the deceased parent before death), several years thereafter (ie, distinctive reflection during adolescence, prompted by the parent's absence) and the present time (ie, unresolved feelings regarding losing the parent). We identified seven themes among the medical professionals (eg, lack of knowledge/experience with children, the family's attempts to shield the child from the reality of death, estrangement from the family once they leave the hospital). CONCLUSIONS: An important finding of the study is that the participants' grief reaction to their parents' deaths during childhood was prolonged. Moreover, hospital medical professionals may find it difficult to directly support affected children. Comprehensive support involving organisations (eg, local communities) may be necessary for children who have lost a parent. PMID- 26847029 TI - BCOR regulates myeloid cell proliferation and differentiation. AB - BCOR is a component of a variant Polycomb group repressive complex 1 (PRC1). Recently, we and others reported recurrent somatic BCOR loss-of-function mutations in myelodysplastic syndrome and acute myelogenous leukemia (AML). However, the role of BCOR in normal hematopoiesis is largely unknown. Here, we explored the function of BCOR in myeloid cells using myeloid murine models with Bcor conditional loss-of-function or overexpression alleles. Bcor mutant bone marrow cells showed significantly higher proliferation and differentiation rates with upregulated expression of Hox genes. Mutation of Bcor reduced protein levels of RING1B, an H2A ubiquitin ligase subunit of PRC1 family complexes and reduced H2AK119ub upstream of upregulated HoxA genes. Global RNA expression profiling in murine cells and AML patient samples with BCOR loss-of-function mutation suggested that loss of BCOR expression is associated with enhanced cell proliferation and myeloid differentiation. Our results strongly suggest that BCOR plays an indispensable role in hematopoiesis by inhibiting myeloid cell proliferation and differentiation and offer a mechanistic explanation for how BCOR regulates gene expression such as Hox genes. PMID- 26847036 TI - The impact of body mass index on semen parameters in infertile men. AB - This hospital-based, prospective study was conducted to evaluate the relationship between body mass index (BMI) and various semen parameters in infertile men. A total of 439 men presented for infertility evaluation were assessed by basic infertility evaluation measures including semen analysis and BMI calculation. The main outcome measure was the relationship between BMI groups [BMI: 18.5-24.9 kg/m2 (normal weight), 25-29.9 kg/m2 (overweight) and >=30 kg/m2 (obese)] and different semen parameters [volume, concentration, motility and morphology]. The mean BMI was 29.67 +/- 5.89. Most of patients (82.91%) were overweight or obese. The 3 BMI groups were comparable in semen parameters (P > 0.05). BMI had a negative correlation with various semen parameters. However, this correlation was significant only with sperm concentration (P = 0.035). We concluded that sperm concentration was the only semen parameter which showed significant reduction with higher BMI in infertile men. PMID- 26847035 TI - Expression of programmed death 1 ligand 1 on periodontal tissue cells as a possible protective feedback mechanism against periodontal tissue destruction. AB - Programmed death 1 ligand 1 (PD-L1) is a negative co-stimulatory molecule in immune responses. Previous reports have indicated that inflammatory cytokines can upregulate the expression of PD-L1 in tumor cells, which in turn suppresses host immune responses. Periodontitis is characterized by persistent inflammation of the periodontium, which is initiated by infection with oral bacteria and results in damage to cells and the matrices of the periodontal connective tissues. In the present study, the expression and function of PD-L1 in periodontal tissue destruction were examined. Periodontal ligament cells (PDLCs) were stimulated by inflammatory cytokines and periodontal pathogens. The expression and function of PD-L1 on the surface of PDLCs was investigated using flow cytometry in vitro. Periodontal disease was induced by the injection of Porphyromonas gingivalis in mouse models. The expression levels of PD-L1 in the periodontal tissues of the mice were analyzed using flow cytometry and immunohistochemistry. PD-L1 was inducibly expressed on the PDLCs by the inflammatory cytokines and periodontal pathogens. The inflammation-induced expression of PD-L1 was shown to cause the apoptosis of activated T lymphocytes and improve the survival of PDLCs. Furthermore, in the mouse model of experimental periodontitis, the expression of PD-L1 in severe cases of periodontitis was significantly lower, compared with that in mild cases. By contrast, no significant differences were observed between the healthy control and severe periodontitis groups. The results of the present study showed that the expression of PD-L1 may inhibit the destruction of periodontal tissues, indicating the involvement of a possible protective feedback mechanism against periodontal infection. PMID- 26847037 TI - A database of body-only computer-generated pictures of women for body-image studies: Development and preliminary validation. AB - The body-shape-related stimuli used in most body-image studies have several limitations (e.g., a lack of pilot validation procedures and the use of non-body shape-related control/neutral stimuli). We therefore developed a database of 61 computer-generated body-only pictures of women, wherein bodies were methodically manipulated in terms of fatness versus thinness. Eighty-two young women assessed the pictures' attractiveness, beauty, harmony (valence ratings), and body shape (assessed on a thinness/fatness axis), providing normative data for valence and body shape ratings. First, stimuli manipulated for fatness versus thinness conveyed comparable emotional intensities regarding the valence and body shape ratings. Second, different subcategories of stimuli were obtained on the basis of variations in body shape and valence judgments. Fat and thin bodies were distributed into several subcategories depending on their valence ratings, and a subcategory containing stimuli that were neutral in terms of valence and body shape was identified. Interestingly, at a descriptive level, the thinness/fatness manipulations of the bodies were in a curvilinear relationship with the valence ratings: Thin bodies were not only judged as positive, but also as negative when their estimated body mass indexes (BMIs) decreased too much. Finally, convergent validity was assessed by exploring the impacts of body-image-related variables (BMI, thin-ideal internalization, and body dissatisfaction) on participants' judgments of the bodies. Valence judgments, but not body shape judgments, were influenced by the participants' levels of thin-ideal internalization and body dissatisfaction. Participants' BMIs did not significantly influence their judgments. Given these findings, this database contains relevant material that can be used in various fields, primarily for studies of body-image disturbance or eating disorders. PMID- 26847038 TI - Framework Cationization by Preemptive Coordination of Open Metal Sites for Anion Exchange Encapsulation of Nucleotides and Coenzymes. AB - Cationic frameworks can selectively trap anions through ion exchange, and have applications in ion chromatography and drug delivery. However, cationic frameworks are much rarer than anionic or neutral ones. Herein, we propose a concept, preemptive coordination (PC), for targeting positively charged metal organic frameworks (P-MOFs). PC refers to proactive blocking of metal coordination sites to preclude their occupation by neutralizing ligands such as OH(-) . We use 20 MOFs to show that this PC concept is an effective approach for developing P-MOFs whose high stability, porosity, and anion-exchange capability allow immobilization of anionic nucleotides and coenzymes, in addition to charge- and size-selective capture or separation of organic dyes. The CO2 and C2 H2 uptake capacity of 117.9 cm(3) g(-1) and 148.5 cm(3) g(-1) , respectively, at 273 K and 1 atm, is exceptionally high among cationic framework materials. PMID- 26847040 TI - A pilot study to image the vascular network of small melanocytic choroidal tumors with speckle noise-free 1050-nm swept source optical coherence tomography (OCT choroidal angiography). AB - PURPOSE: To visualize and measure the vascular network of melanocytic choroidal tumors with speckle noise-free swept source optical coherence tomography (SS-OCT choroidal angiography). METHODS: Melanocytic choroidal tumors from 24 eyes were imaged with 1050-nm optical coherence tomography (Topcon DRI OCT-1 Atlantis). A semi-automated algorithm was developed to remove speckle noise and to extract and measure the volume of the choroidal vessels from the obtained OCT data. RESULTS: In all cases, analysis of the choroidal vessels could be performed with SS-OCT without the need for pupillary dilation. The proposed method allows speckle noise free, structure-guided visualization and measurement of the larger choroidal vessels in three dimensions. The obtained data suggest that speckle noise-free OCT may be more effective at identifying choroidal structures than traditional OCT methods. The measured volume of the extracted choroidal vessels of Haller's layer and Sattler's layer in the examined tumorous eyes was on average 0.982463955 mm(3) /982463956 MUm(3) (range of 0.209764406 mm(3) /209764405.9 MUm(3)to 1.78105544 mm(3) /1781055440 MUm(3)). Full thickness obstruction of the choroidal vasculature by the tumor was found in 18 cases (72 %). In seven cases (18 %), choroidal vessel architecture did not show pronounced morphological abnormalities (18 %). CONCLUSION: Speckle noise-free OCT may serve as a new illustrative imaging technology and enhance visualization of the choroidal vessels without the need for dye injection. OCT can be used to identify and evaluate the choroidal vessels of melanocytic choroidal tumors, and may represent a potentially useful tool for imaging and monitoring of choroidal nevi and melanoma. PMID- 26847039 TI - Relative changes in luminal and stromal areas of choroid determined by binarization of EDI-OCT images in eyes with Vogt-Koyanagi-Harada disease after treatment. AB - PURPOSE: The aim of this study was to determine the changes in the luminal and stromal areas of the choroid in eyes with Vogt-Koyanagi-Harada disease by optical coherence tomography (OCT). METHODS: A retrospective observational study. Choroidal images were recorded by enhanced depth imaging (EDI-OCT) at the baseline, and at 1 week and 1 month after initiating steroid therapy. The EDI-OCT images were converted to binarized images, and the luminal areas and the stromal areas were measured separately. RESULTS: Thirty-two eyes of 16 patients were enrolled, and 16 eyes of 10 patients had suitable images for the binarization analyses. The ratio of the luminal areas to the choroidal areas was 0.60 +/- 0.03 at the baseline, 0.67 +/- 0.04 at 1 week, and 0.66 +/- 0.04 at 1 month. There was a significant increase from the baseline at 1 week (P < 0.01) but not from 1 week to 1 month. Although both the stromal and luminal areas were reduced, the percent reduction of the stromal areas (56.5 +/- 7.2 %) was significantly greater than that of the luminal areas (42.5 +/- 12.6 %) at 1 week (P < 0.01). CONCLUSIONS: A significant decrease of the choroidal area was detected in eyes with Vogt Koyanagi-Harada disease at 1 week after beginning steroid therapy. The decrease was more evident in the stromal area than in the luminal area. PMID- 26847042 TI - PI-RADS version 2 for prediction of pathological downgrading after radical prostatectomy: a preliminary study in patients with biopsy-proven Gleason Score 7 (3+4) prostate cancer. AB - OBJECTIVES: To evaluate PI-RADSv2 for predicting pathological downgrading after radical prostatectomy (RP) in patients with biopsy-proven Gleason score (GS) 7(3+4) PC. METHODS: A total of 105 patients with biopsy-proven GS 7(3+4) PC who underwent multiparametric prostate MRI followed by RP were included. Two radiologists assigned PI-RADSv2 scores for each patient. Preoperative clinicopathological variables and PI-RADSv2 scores were compared between patients with and without downgrading after RP using the Wilcoxon rank sum test or Fisher's exact test. Logistic regression analyses with Firth's bias correction were performed to assess their association with downgrading. RESULTS: Pathological downgrading was identified in ten (9.5 %) patients. Prostate specific antigen (PSA), PSA density, percentage of cores with GS 7(3+4), and greatest percentage of core length (GPCL) with GS 7(3+4) were significantly lower in patients with downgrading (p = 0.002-0.037). There was no significant difference in age and clinical stage (p = 0.537-0.755). PI-RADSv2 scores were significantly lower in patients with downgrading (3.8 versus 4.4, p = 0.012). At univariate logistic regression analysis, PSA, PSA density, and PI-RADSv2 scores were significant predictors of downgrading (p = 0.003-0.022). Multivariate analysis revealed only PSA density and PI-RADSv2 scores as independent predictors of downgrading (p = 0.014-0.042). CONCLUSIONS: The PI-RADSv2 scoring system was an independent predictor of pathological downgrading after RP in patients with biopsy-proven GS 7(3+4) PC. KEY POINTS: * PI-RADSv2 was an independent predictor of downgrading in biopsy-proven GS 7(3+4) PC * PSA density was also an independent predictor of downgrading * MRI may assist in identifying AS candidates in biopsy-proven GS 7(3+4) PC patients. PMID- 26847041 TI - Cardiac magnetic resonance findings predicting mortality in patients with pulmonary arterial hypertension: a systematic review and meta-analysis. AB - OBJECTIVES: To provide a comprehensive overview of all reported cardiac magnetic resonance (CMR) findings that predict clinical deterioration in pulmonary arterial hypertension (PAH). METHODS: MEDLINE and EMBASE electronic databases were systematically searched for longitudinal studies published by April 2015 that reported associations between CMR findings and adverse clinical outcome in PAH. Studies were appraised using previously developed criteria for prognostic studies. Meta-analysis using random effect models was performed for CMR findings investigated by three or more studies. RESULTS: Eight papers (539 patients) investigating 21 different CMR findings were included. Meta-analysis showed that right ventricular (RV) ejection fraction was the strongest predictor of mortality in PAH (pooled HR 1.23 [95 % CI 1.07-1.41], p = 0.003) per 5 % decrease. In addition, RV end-diastolic volume index (pooled HR 1.06 [95 % CI 1.00-1.12], p = 0.049), RV end-systolic volume index (pooled HR 1.05 [95 % CI 1.01-1.09], p = 0.013) and left ventricular end-diastolic volume index (pooled HR 1.16 [95 % CI 1.00-1.34], p = 0.045) were of prognostic importance. RV and LV mass did not provide prognostic information (p = 0.852 and p = 0.983, respectively). CONCLUSION: This meta-analysis substantiates the clinical yield of specific CMR findings in the prognostication of PAH patients. Decreased RV ejection is the strongest and most well established predictor of mortality. KEY POINTS: * Cardiac magnetic resonance imaging is useful for prognostication in pulmonary arterial hypertension. * Right ventricular ejection fraction is the strongest predictor of mortality. * Serial CMR evaluation seems to be of additional prognostic importance. * Accurate prognostication can aid in adequate and timely intensification of PAH-specific therapy. PMID- 26847043 TI - Gouty arthritis: the diagnostic and therapeutic impact of dual-energy CT. AB - OBJECTIVES: To determine the diagnostic and therapeutic impact of dual-energy computed tomography (DECT) in gout. METHODS: Forty-three patients with (n = 20) and without a history of gout (n = 23) showing non-specific soft tissue deposits underwent DECT after unrewarding arthrocentesis. Two blinded, independent readers evaluated DECT for the presence of urate crystals. Clinical diagnosis, clinically suspected urate crystal locations, diagnostic thinking and therapeutic decisions were noted before and after DECT. Clinical 1-month follow-up was obtained. RESULTS: DECT showed urate in 26/43 patients (60 %). After DECT, clinical diagnosis of gout was withdrawn in 17/43 (40 %) and was maintained in 16/43 patients (37 %). In 10/43 patients (23 %) the diagnosis was maintained, but DECT revealed urate in clinically unsuspected locations. In 23/43 patients (53 %), a treatment-change based on DECT occurred. Changes in diagnostic thinking occurred more frequently in patients without a history of gout (p < 0.001), changes in therapeutic decisions more frequently in patients with a history of gout (p = 0.014). Clinical follow-up indicated beneficial effects of DECT-based diagnoses in 83 % of patients. CONCLUSIONS: In patients with or without a history of gout and a recent suspicion for gouty arthritis with an unrewarding arthrocentesis, DECT has a marked diagnostic and therapeutic impact when hyperdense soft-tissue deposits are present. KEY POINTS: * This study evaluates the concept of evidence based radiology * In patients with suspected gout, DECT can help clinicians make the diagnosis * DECT has a marked impact on therapy * Clinical follow-up after 1 month indicated reliable results of DECT. PMID- 26847045 TI - Inhibition of Candida albicans biofilm formation and modulation of gene expression by probiotic cells and supernatant. AB - Oral candidiasis is a disease caused by opportunistic species of Candida that normally reside on human mucosal surfaces. The transition of Candida from budding yeast to filamentous hyphae allows for covalent attachment to oral epithelial cells, followed by biofilm formation, invasion and tissue damage. In this study, combinations of Lactobacillus plantarum SD5870, Lactobacillus helveticus CBS N116411 and Streptococcus salivarius DSM 14685 were assessed for their ability to inhibit the formation of and disrupt Candida albicans biofilms. Co-incubation with probiotic supernatants under hyphae-inducing conditions reduced C. albicans biofilm formation by >75 % in all treatment groups. Likewise, combinations of live probiotics reduced biofilm formation of C. albicans by >67 %. When live probiotics or their supernatants were overlaid on preformed C. albicans biofilms, biofilm size was reduced by >63 and >65 % respectively. Quantitative real-time PCR results indicated that the combined supernatants of SD5870 and CBS N116411 significantly reduced the expression of several C. albicans genes involved in the yeast-hyphae transition: ALS3 (adhesin/invasin) by 70 % (P < 0.0001), EFG1 (hyphae-specific gene activator) by 47 % (P = 0.0061), SAP5 (secreted protease) by 49 % (P < 0.0001) and HWP1 (hyphal wall protein critical to biofilm formation) by >99 % (P < 0.0001). These findings suggest the combination of L. plantarum SD5870, L. helveticus CBS N116411 and S. salivarius DSM 14685 is effective at both preventing the formation of and removing preformed C. albicans biofilms. Our novel results point to the downregulation of several Candida genes critical to the yeast-hyphae transition, biofilm formation, tissue invasion and cellular damage. PMID- 26847044 TI - Automated tube voltage selection for radiation dose and contrast medium reduction at coronary CT angiography using 3(rd) generation dual-source CT. AB - OBJECTIVES: To investigate the relationship between automated tube voltage selection (ATVS) and body mass index (BMI) and its effect on image quality and radiation dose of coronary CT angiography (CCTA). METHODS: We evaluated 272 patients who underwent CCTA with 3(rd) generation dual-source CT (DSCT). Prospectively ECG-triggered spiral acquisition was performed with automated tube current selection and advanced iterative reconstruction. Tube voltages were selected by ATVS (70-120 kV). BMI, effective dose (ED), and vascular attenuation in the coronary arteries were recorded. Signal-to-noise ratio (SNR) and contrast to-noise ratio (CNR) were calculated. Five-point scales were used for subjective image quality analysis. RESULTS: Image quality was rated good to excellent in 98.9 % of examinations without significant differences for proximal and distal attenuation (all p >= .0516), whereas image noise was rated significantly higher at 70 kV compared to >=100 kV (all p < .0266). However, no significant differences were observed in SNR or CNR at 70-120 kV (all p >= .0829). Mean ED at 70-120 kV was 1.5 +/- 1.2 mSv, 2.4 +/- 1.5 mSv, 3.6 +/- 2.7 mSv, 5.9 +/- 4.0 mSv, 7.9 +/- 4.2 mSv, and 10.7 +/- 4.1 mSv, respectively (all p <= .0414). Correlation analysis showed a moderate association between tube voltage and BMI (r = .639). CONCLUSION: ATVS allows individual tube voltage adaptation for CCTA performed with 3(rd) generation DSCT, resulting in significantly decreased radiation exposure while maintaining image quality. KEY POINTS: * Automated tube voltage selection allows an individual tube voltage adaption in CCTA. * A tube voltage based reduction of contrast medium volume is feasible. * Image quality was maintained while radiation exposure was significantly decreased. * A moderate association between tube voltage and body mass index was found. PMID- 26847046 TI - Effects of the Staff Training for Assisted Living Residences protocol for caregivers of older adults with dementia: A pilot study in the Brazilian population. AB - AIM: To investigate the effects of the Staff Training for Assisted Living Residences administered to formal caregivers of older adults with behavioral and psychological symptoms of dementia in the institutional environment. METHODS: The project was developed in two long-term care institutions in Belo Horizonte, Brazil, with 25 formal caregivers and 46 older adults with dementia. The training was carried out over 6 weeks. Evaluations were carried out with the caregivers and the elderly residents, using specific instruments to evaluate different domains (demographic data, etiological diagnoses of dementia, severity of dementia, global cognition, functional performance, quality of life, behavior, burden of caregiver, depression and anxiety). The total time for data collection was 6 months. RESULTS: A significant improvement in behavioral and psychological symptoms of dementia, as assessed by the Neuropsychiatric Inventory, was observed (P < 0.008), with no changes in the other indexes. No significant changes were observed in parameters related to caregivers. CONCLUSIONS: The Staff Training for Assisted Living Residences protocol was effective in reducing neuropsychiatric symptoms in dementia patients, and might be a feasible and positive strategy to train formal caregivers in long-term care institutions in Brazil. Geriatr Gerontol Int 2017; 17: 449-455. PMID- 26847048 TI - Transformation-optical Fan-beam Synthesis. AB - Gradient-index dielectric lenses are generated based on the coordinate transformation by compressing the homogeneous air spaces quasi-conformally towards and outwards the primary source. The three-dimensional modeling is then performed through revolving the prescribed transformational media 180 degrees around the focal point to reach the architecture of barrel-vaults. It is found that all these two- and three-dimensional transformation-optical designs are capable of producing fan-beams efficiently over a broad frequency range with their main lobes possessing the narrow beamwidth in one dimension and the wide beamwidth in the other, while having the great ability of the wide angular scanning. Finally, we propose to construct such four types of fan-beam lenses through multiple-layered dielectrics with non-uniformed perforations and experimentally demonstrate their excellent performances in the fan-beam synthesis. PMID- 26847049 TI - The utility of the high-resolution ultrasound technique in the evaluation of autologous adipose tissue lipofilling, used for the correction of post-surgical, post-traumatic and post-burn scars. AB - PURPOSE: Lipofilling technique is significantly increasing and the need of a non invasive method to assess the success of the procedure is becoming mandatory. In particular, US can be considered an alternative method to MRI for evaluation of tissue lipofilling due to the simplicity and easy access of the technique and can be also used for monitoring the efficacy of the surgical procedure. The goal of this study was to demonstrate, the utility of the high-resolution ultrasound technique in the evaluation of autologous adipose tissue lipofilling, used for the correction of post-surgical, post-traumatic and post-burn scars. MATERIALS AND METHODS: Twenty-five patients (21 females), aged between 14 and 62 years, underwent surgical correction of scars with ''lipofilling'' technique. To evaluate the effectiveness of such treatment serial ultrasound examinations were performed at both the region affected from skin dimorphism through the adjacent skin region, using a high frequency transducer. Furthermore, it was assessed the presence of complications ranging from oedema or hematoma to necrosis or adipocyte migration of the graft. Finally, was calculated the average percentage of one-year survival of autologous fat transplant. RESULTS: Quantitative evaluations obtained with time series of ultrasound showed that the greatest benefits of autologous adipose tissue lipofilling, are found at the level of the hypodermis, but that also all the other layers of the skin can benefit from this procedure. CONCLUSION: The data acquired demonstrate that the eco color Doppler with high resolution can be considered a valid non-invasive tool for the assessment of morphological and quantitative degree of engraftment of autologous adipose tissue transplanted. Lipofilling is an accurate and effective choice for the correction of congenital or acquired skin disorders for its filler effect and consequent benefit for all tissue layers. PMID- 26847050 TI - Are abdominal aortic aneurysms with hostile neck really unsuitable for EVAR? Our experience. AB - OBJECTIVE: To evaluate the effectiveness of endovascular treatment of abdominal aortic aneurysms with hostile neck, comparing the results with those of patients with ideal anatomical conditions. MATERIALS AND METHODS: From January 2005 to December 2013, 300 patients were treated with EVAR at our institution. Patients with a prior Angio-CT scan were included in the study and they were then retrospectively divided into two groups: patients with suitable anatomy that were treated within guidelines of the manufacturers (wIFU: 94 patients, four treated in emergency) and those with unsuitable anatomy that were treated outside of said guidelines (oIFU: 70 patients, 16 treated in emergency). Patients without prior CT study and without follow-up were excluded from the study. RESULTS: Postoperative mortality was 6.3 % in the wIFU group while it was 7.8 % in the oIFU group. There was not a statistically significant difference in the rate of postoperative mortality (p = 0.653). Technical success was 98.6 % in the wIFU group while it was 94.5 % in the oIFU group. All the patients of the wIFU group were treated with a stent-graft with under-renal sealing while in the oIFU group always an over-renal stent-graft was used. No deaths related to the aneurysm were highlighted at follow-up in both groups. There was a statistically significative difference between the two groups regarding intraoperative occlusion of renal arteries (wIFU = 1.1 %; oIFU = 4.7 %; p < 0.05) and in the development of type I endoleak (wIFU = 2.8 %; oIFU = 8.8 %; p < 0.05) CONCLUSION: EVAR in patients with hostile neck is feasible and effective with an acceptable rate of complications. PMID- 26847051 TI - Implications of immortal person-time when outcomes are nonfatal. AB - PURPOSE: The amount of immortal time bias in studies with nonfatal outcomes is unclear. To quantify the magnitude of bias from mishandling of immortal person time in studies of nonfatal outcomes. METHODS: We derived formulas for quantifying bias from misclassified or excluded immortal person-time in settings with nonfatal outcomes, assuming a constant rate of outcome. In the situation of misclassified or excluded immortal person-time, the quantification includes the immortal time and corresponding events mistakenly attributed to the exposed group (misclassified) or excluded from study (excluded) that must be attributed to the comparison group. RESULTS: With misclassified immortal person-time, the magnitude of bias varies according to the incidence rate ratio of immortal time and comparison group as well as the rate ratio of immortal time and exposed group: toward null for both ratios less than 1, no bias for both ratios equal to 1, away from null for both ratios greater than 1. For one ratio less than 1 and the other greater than 1, the direction and magnitude of bias can be obtained from the formula provided. With excluded immortal person-time, the magnitude of bias is associated with the incidence rate ratio of immortal time and comparison group: toward null for the ratio less than 1, no bias for the ratio equal to 1, and away from null for the ratio greater than 1. CONCLUSIONS: Bias due to immortal person time in studies with nonfatal outcomes can vary widely and can be quantified under assumptions that apply to many studies. PMID- 26847047 TI - Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. AB - RATIONALE: Psychosocial stressors are a well-documented risk factor for mental illness. Neuroinflammation, in particular elevated microglial activity, has been proposed to mediate this association. A number of preclinical studies have investigated the effect of stress on microglial activity. However, these have not been systematically reviewed before. OBJECTIVES: This study aims to systematically review the effects of stress on microglia, as indexed by the histological microglial marker ionised calcium binding adaptor molecule 1 (Iba 1), and consider the implications of these for the role of stress in the development of mental disorders. METHODS: A systematic review was undertaken using pre-defined search criteria on PubMed and EMBASE. Inclusion and data extraction was agreed by two independent researchers after review of abstracts and full text. RESULTS: Eighteen studies met the inclusion criteria. These used seven different psychosocial stressors, including chronic restraint, social isolation and repeated social defeat in gerbils, mice and/or rats. The hippocampus (11/18 studies) and prefrontal cortex (13/18 studies) were the most frequently studied areas. Within the hippocampus, increased Iba-1 levels of between 20 and 200 % were reported by all 11 studies; however, one study found this to be a duration-dependent effect. Of those examining the prefrontal cortex, ~75 % found psychosocial stress resulted in elevated Iba-1 activity. Elevations were also consistently seen in the nucleus accumbens, and under some stress conditions in the amygdala and paraventricular nucleus. CONCLUSIONS: There is consistent evidence that a range of psychosocial stressors lead to elevated microglial activity in the hippocampus and good evidence that this is also the case in other brain regions. These effects were seen with early-life/prenatal stress, as well as stressors in adulthood. We consider these findings in terms of the two-hit hypothesis, which proposes that early-life stress primes microglia, leading to a potentiated response to subsequent stress. The implications for understanding the pathoaetiology of mental disorders and the development of new treatments are also considered. PMID- 26847052 TI - Disentangling rectangularization and life span extension with the moving rectangle method. AB - PURPOSE: The moving rectangle method is used to disentangle the contributions of rectangularization and life span extension to the increase in life expectancy. It requires the choice of an endpoint of the survival curve that approaches the maximum age at death. We examined the effect of choosing different end points on the outcomes of this method. METHODS: For five developed countries, survival curves from age 50 years were constructed per calendar year from 1922 onward. Survival values of 0.1, 0.01, and 0.001 were chosen as end points of the survival curve, and the contributions of rectangularization and life span extension to the increase in life expectancy were calculated using the moving rectangle method. RESULTS: The choice of different survival values as end points profoundly influenced the estimated contributions of rectangularization and life span extension to the increase in life expectancy. When choosing 0.001, rectangularization contributed most years, whereas when choosing 0.1, life span extension contributed most years. CONCLUSIONS: When the moving rectangle method is used to estimate the contributions of rectangularization and life span extension to the increase in life expectancy, its outcomes depend on the choice of the endpoint of the survival curve. PMID- 26847053 TI - MET Amplification and Exon 14 Splice Site Mutation Define Unique Molecular Subgroups of Non-Small Cell Lung Carcinoma with Poor Prognosis. AB - PURPOSE: Activation of MET oncogene as the result of amplification or activation mutation represents an emerging molecular target for cancer treatment. We comprehensively studied MET alterations and the clinicopathologic correlations in a large cohort of treatment-naive non-small cell lung carcinoma (NSCLC). EXPERIMENTAL DESIGN: Six hundred eighty-seven NSCLCs were tested for MET exon 14 splicing site mutation (METDelta14), DNA copy number alterations, and protein expression by Sanger sequencing, FISH, and IHC, respectively. RESULTS: METDelta14 mutation was detected in 2.62% (18/687) of NSCLC. The mutation rates were 2.6% in adenocarcinoma, 4.8% in adenosquamous carcinoma, and 31.8% in sarcomatoid carcinoma. METDelta14 mutation was not detected in squamous cell carcinoma, large cell carcinoma, and lymphoepithelioma-like carcinoma but significantly enriched in sarcomatoid carcinoma (P < 0.001). METDelta14 occurred mutually exclusively with known driver mutations but tended to coexist with MET amplification or copy number gain (P < 0.001). Low-level MET amplification and polysomy might occur in the background of EGFR or KRAS mutation whereas high-level amplification (MET/CEP7 ratio >=5) was mutually exclusive to the major driver genes except METDelta14. Oncogenic METDelta14 mutation and/or high-level amplification occurred in a total of 3.3% (23/687) of NSCLC and associated with higher MET protein expression. METDelta14 occurred more frequently in older patients whereas amplification was more common in ever-smokers. Both METDelta14 and high-level amplification were independent prognostic factors that predicted poorer survival by multivariable analysis. CONCLUSIONS: The high incidence of METDelta14 mutation in sarcomatoid carcinoma suggested that MET inhibition might benefit this specific subgroup of patients. Clin Cancer Res; 22(12); 3048-56. (c)2016 AACRSee related commentary by Drilon, p. 2832. PMID- 26847054 TI - Dose Escalation of Tamoxifen in Patients with Low Endoxifen Level: Evidence for Therapeutic Drug Monitoring-The TADE Study. AB - PURPOSE: Endoxifen is the major mediator of tamoxifen effect and endoxifen levels <15 nmol/L may be associated with increased risk of breast cancer recurrence. We increased tamoxifen dose in breast cancer patients with low endoxifen levels and assessed the influence of various parameters on reaching 15 nmol/L and 30 nmol/L endoxifen levels. EXPERIMENTAL DESIGN: Tamoxifen dose was increased in those with endoxifen levels below 30 nmol/L. Toxicity, including hot flash score, was measured. CYP2D6 metabolizer status was classified as ultra-rapid (UM), extensive (EM), intermediate (IM), or poor (PM) based genotype of somatic DNA. RESULTS: Dosage was escalated in 68 of 122 participants. On 20 mg tamoxifen, 24% had endoxifen levels below 15 nmol/L and this reduced to 6% following dose escalation. In over 50% of cases, there was no identified cause for low endoxifen. Low baseline endoxifen level, and not CYP2D6 metabolizer status, independently predicted reaching threshold targets for both the 15 nmol/L and 30 nmol/L targets (P = 0.04 and 0.003 respectively). The 15 nmol/L target was reached in all UM/EM and IM patients, 63% of PM patients, and 58% of those with baseline endoxifen of <10 nmol/L. There was no correlation between hot flash score and genotype or any tamoxifen metabolite level including endoxifen (R = 0.07). CONCLUSIONS: Low endoxifen on standard dose tamoxifen was the only independent predictor of failure to achieve potentially therapeutic levels. Trials examining tamoxifen dose escalation and breast cancer outcome should be guided by endoxifen levels alone, without reference to CYP2D6 genotype or presence of hot flashes. Clin Cancer Res; 22(13); 3164-71. (c)2016 AACRSee related commentary by Hertz and Rae, p. 3121. PMID- 26847055 TI - Circulating DNA as a Strong Multimarker Prognostic Tool for Metastatic Colorectal Cancer Patient Management Care. AB - PURPOSE: Circulating cell-free DNA (ccfDNA) is a valuable source of tumor material obtained from a simple blood sampling that enables noninvasive analysis of the tumor genome. Our goal was to carry out a multiparametric analysis of ccfDNA and evaluate its prognostic value by investigating the overall survival (OS) of 97 metastatic colorectal cancer patients (mCRC). EXPERIMENTAL DESIGN: Qualitative parameters (determination of the main KRAS exon2 and BRAF V600E mutations) and quantitative parameters (total ccfDNA concentration, mutant ccfDNA concentration, the proportion of mutant ccfDNA, and ccfDNA integrity index) were determined simultaneously in a single run using a unique Q-PCR multimarker approach (100% success rate). RESULTS: The median follow-up time was 36 months and median OS was 22 months. Patients showing high ccfDNA levels had significantly shorter OS (18.07 months vs. 28.5 months, P = 0.0087). Moreover, multivariate analysis revealed that a high ccfDNA level is an independent prognostic factor (P = 0.034). All ccfDNA parameters were of prognostic interest: patients with higher levels of mutant ccfDNA and higher mutation loads for the detected mutations had shorter OS (P = 0.0089 and P = 0.05, respectively). In addition, the level of ccfDNA fragmentation correlated positively with decreased OS in the exclusive KRAS/BRAF-mutant cohort of patients (P = 0.0052) and appeared as a strong independent prognostic factor (P = 0.0072), whereas it was not significant in the exclusive KRAS/BRAF WT cohort of patients (P = 0.67). CONCLUSIONS: Our data provide for the first time qualitative and quantitative evidence in favor of multiparametric ccfDNA analysis in mCRC patients for prognostic assessment. Clin Cancer Res; 22(12); 3067-77. (c)2016 AACR. PMID- 26847057 TI - Phase I Study of PSMA-Targeted Docetaxel-Containing Nanoparticle BIND-014 in Patients with Advanced Solid Tumors. AB - PURPOSE: First-in-human phase I trial to determine the safety, pharmacokinetics, and antitumor activity of BIND-014, a novel, tumor prostate-specific membrane antigen (PSMA)-targeted nanoparticle, containing docetaxel. EXPERIMENTAL DESIGN: Patients with advanced solid tumors received BIND-014 every three weeks (n = 28) or weekly (n = 27), with dose levels ranging from 3.5 to 75 mg/m(2) and 15 to 45 mg/m(2), respectively. RESULTS: BIND-014 was generally well tolerated, with no unexpected toxicities. The most common drug-related toxicities (>20% of patients) on either schedule included neutropenia, fatigue, anemia, alopecia, and diarrhea. BIND-014 demonstrated a dose-linear pharmacokinetic profile, distinct from docetaxel, with prolonged persistence of docetaxel-encapsulated circulating nanoparticles. Of the 52 patients evaluable for response, one had a complete response (cervical cancer on the every three week schedule) and five had partial responses (ampullary adenocarcinoma, non-small cell lung, and prostate cancers on the every-three-week schedule, and breast and gastroesophageal cancers on the weekly schedule). Responses were noted in both PSMA-detectable and -undetectable tumors. CONCLUSIONS: BIND-014 was generally well tolerated, with predictable and manageable toxicity and a unique pharmacokinetic profile compared with conventional docetaxel. Clinical activity was noted in multiple tumor types. The recommended phase II dose of BIND-014 is 60 mg/m(2) every three weeks or 40 mg/m(2) weekly. Clin Cancer Res; 22(13); 3157-63. (c)2016 AACR. PMID- 26847056 TI - IL15 Trispecific Killer Engagers (TriKE) Make Natural Killer Cells Specific to CD33+ Targets While Also Inducing Persistence, In Vivo Expansion, and Enhanced Function. AB - PURPOSE: The effectiveness of NK cell infusions to induce leukemic remission is limited by lack of both antigen specificity and in vivo expansion. To address the first issue, we previously generated a bispecific killer engager (BiKE) containing single-chain scFv against CD16 and CD33 to create an immunologic synapse between NK cells and CD33(+) myeloid targets. We have now incorporated a novel modified human IL15 crosslinker, producing a 161533 trispecific killer engager (TriKE) to induce expansion, priming, and survival, which we hypothesize will enhance clinical efficacy. EXPERIMENTAL DESIGN: Reagents were tested in proliferation and functional assays and in an in vivo xenograft model of AML. RESULTS: When compared with the 1633 BiKE, the 161533 TriKE induced superior NK cell cytotoxicity, degranulation, and cytokine production against CD33(+) HL-60 targets and increased NK survival and proliferation. Specificity was shown by the ability of a 1615EpCAM TriKE to kill CD33-EpCAM(+) targets. Using NK cells from patients after allogeneic stem cell transplantation when NK cell function is defective, the 161533 TriKE restored potent NK function against primary AML targets and induced specific NK cell proliferation. These results were confirmed in an immunodeficient mouse HL-60-Luc tumor model where the 161533 TriKE exhibited superior antitumor activity and induced in vivo persistence and survival of human NK cells for at least 3 weeks. CONCLUSIONS: Off-the-shelf 161533 TriKE imparts antigen specificity and promotes in vivo persistence, activation, and survival of NK cells. These qualities are ideal for NK cell therapy of myeloid malignancies or targeting antigens of solid tumors. Clin Cancer Res; 22(14); 3440-50. (c)2016 AACRSee related commentary by Talmadge, p. 3419. PMID- 26847058 TI - Impact of Genes Highly Correlated with MMSET Myeloma on the Survival of Non-MMSET Myeloma Patients. AB - PURPOSE: The poor prognosis of multiple myeloma with t(4;14) is driven by the fusion of genes encoding multiple myeloma SET domain (MMSET) and immunoglobulin heavy chain. Specific genes affected by MMSET and their clinical implications in non-MMSET myeloma remain undetermined. EXPERIMENTAL DESIGN: We obtained gene expression profiles of 1,032 newly diagnosed myeloma patients enrolled in Total Therapy 2, Total Therapy 3, Myeloma IX, and HOVON65-GMMGHD4 trials and 156 patients from Multiple Myeloma Resource Collection. Probes that correlated most with MMSET myeloma were selected on the basis of a multivariable linear regression and Bonferroni correction and refined on the basis of the strength of association with survival in non-MMSET patients. RESULTS: Ten MMSET-like probes were associated with poor survival in non-MMSET myeloma. Non-MMSET myeloma patients in the highest quartile of the 10-gene signature (MMSET-like myeloma) had 5-year overall survival similar to that of MMSET myeloma [highest quartile vs. lowest quartile HR = 2.0; 95% confidence interval (CI), 1.5-2.8 in MMSET-like myeloma; HR = 2.3; 95% CI, 1.6-3.3 in MMSET myeloma]. Analyses of MMSET-like gene signature suggested the involvement of p53 and MYC pathways. CONCLUSIONS: MMSET like gene signature captures a subset of high-risk myeloma patients underrepresented by conventional risk stratification platforms and defines a distinct biologic subtype. Clin Cancer Res; 22(16); 4039-44. (c)2016 AACR. PMID- 26847059 TI - Notch1 Signaling Regulates the Aggressiveness of Differentiated Thyroid Cancer and Inhibits SERPINE1 Expression. AB - PURPOSE: Notch1, a transmembrane receptor, has been recently shown to aid in the determination of thyroid cell fate associated with tumorigenesis. This study aimed to investigate the clinical relevance of Notch1 and its role in the regulation of differentiated thyroid cancer (DTC) behavior. EXPERIMENTAL DESIGN: We examined Notch1 expression level and its relationship with clinicopathologic features and outcomes of DTC. Notch1 intracellular domain (NICD) was further characterized both in vitro and in vivo by gain-of-function assays using an inducible system. RESULTS: Notch1 expression levels were downregulated in primary DTC tissue samples compared with contralateral nontumor and benign thyroid tissues. Decreased Notch1 expression in DTC was associated with advanced patient age (P = 0.032) and the presence of extrathyroidal invasion (P = 0.005). Patients with lower Notch1 expression had a significantly higher recurrence rate (P = 0.038). Restoration of NICD in a stably doxycycline-inducible metastatic DTC cell line reduced cell growth and migration profoundly. Using an orthotopic thyroid cancer model, NICD induction significantly reduced the growth of the primary thyroid tumor and inhibited the development of lung metastasis. Serpin peptidase inhibitor, clade E, member 1 (SERPINE1) was discovered by microarray as the most significant gene downregulated by NICD. Further validation showed that the induction of NICD reduced SERPINE1 expression in a dose-dependent manner, whereas restoration of a relative higher level of SERPINE1 was observed with NICD back to minimal level. In addition, SERPINE1 knock-down inhibited DTC cell migration. CONCLUSIONS: Notch1 regulates the aggressive phenotypes of DTC, which could be mediated by SERPINE1 inhibition. Notch1/SERPINE1 axis warrants further investigation as a novel therapeutic target for advanced DTC. Clin Cancer Res; 22(14); 3582-92. (c)2016 AACR. PMID- 26847060 TI - Arresting the Inflammatory Drive of Chronic Lymphocytic Leukemia with Ibrutinib. AB - The clinical success of agents targeting the B-cell receptor signaling pathway in chronic lymphocytic leukemia (CLL) may also derive from disrupting the CLL microenvironment. Investigation of the immunomodulatory effects of these agents illuminates the unique immunobiology of CLL and highlights potential targets for dismantling the chronic inflammatory drive. See related article by Niemann et al., p. 1572. PMID- 26847063 TI - Blood's 70th anniversary: reflections of a past editor, 1983-1987. PMID- 26847064 TI - Reissmann KR. Studies on the mechanism of erythropoietic stimulation in parabiotic rats during hypoxia. AB - The articles featured in the Blood Flashback series were selected and the commentaries written by the Blood Editors. Complete versions of all the articles in the series, commemorating the journal's 70th-anniversary year, can be found on the Blood Web site at www.bloodjournal.org/collection/blood-flashback. In this historic study, Kurt R. Reissmann used parabiotic rats to demonstrate the functional existence of erythropoietin. In a crossed circulation setting, 1 rat was kept in conditions of hypoxia and the other in normal oxygen. Both rats developed reticulocytosis, increased hemoglobin, and bone marrow hyperplasia. He concluded that erythropoiesis is regulated by a humoral factor rather than by a direct oxygen effect on the bone marrow. Following this pivotal work, the role of the kidney in erythropoiesis was shown by Leon Jacobson in 1957 and erythropoietin was eventually purified from the urine of anemic patients by Eugene Goldwasser in 1977. Parabiotic experiments are still used and were recently applied to investigate aging and rejuvenation related to systemic factors. PMID- 26847062 TI - Capturing patients' needs in casemix: a systematic literature review on the value of adding functioning information in reimbursement systems. AB - BACKGROUND: Contemporary casemix systems for health services need to ensure that payment rates adequately account for actual resource consumption based on patients' needs for services. It has been argued that functioning information, as one important determinant of health service provision and resource use, should be taken into account when developing casemix systems. However, there has to date been little systematic collation of the evidence on the extent to which the addition of functioning information into existing casemix systems adds value to those systems with regard to the predictive power and resource variation explained by the groupings of these systems. Thus, the objective of this research was to examine the value of adding functioning information into casemix systems with respect to the prediction of resource use as measured by costs and length of stay. METHODS: A systematic literature review was performed. Peer-reviewed studies, published before May 2014 were retrieved from CINAHL, EconLit, Embase, JSTOR, PubMed and Sociological Abstracts using keywords related to functioning ('Functioning', 'Functional status', 'Function*, 'ICF', 'International Classification of Functioning, Disability and Health', 'Activities of Daily Living' or 'ADL') and casemix systems ('Casemix', 'case mix', 'Diagnosis Related Groups', 'Function Related Groups', 'Resource Utilization Groups' or 'AN-SNAP'). In addition, a hand search of reference lists of included articles was conducted. Information about study aims, design, country, setting, methods, outcome variables, study results, and information regarding the authors' discussion of results, study limitations and implications was extracted. RESULTS: Ten included studies provided evidence demonstrating that adding functioning information into casemix systems improves predictive ability and fosters homogeneity in casemix groups with regard to costs and length of stay. Collection and integration of functioning information varied across studies. Results suggest that, in particular, DRG casemix systems can be improved in predicting resource use and capturing outcomes for frail elderly or severely functioning-impaired patients. CONCLUSION: Further exploration of the value of adding functioning information into casemix systems is one promising approach to improve casemix systems ability to adequately capture the differences in patient's needs for services and to better predict resource use. PMID- 26847061 TI - Salivary Biomarkers for Detection of Oral Squamous Cell Carcinoma in a Taiwanese Population. AB - PURPOSE: This study evaluated the discriminatory power of salivary transcriptomic and proteomic biomarkers in distinguishing oral squamous cell carcinoma cases from controls and potentially malignant oral disorders (PMOD). EXPERIMENTAL DESIGN: A total of 180 samples (60 OSCC patients, 60 controls, and 60 PMOD patients) were used in the study. Seven transcriptomic markers (IL8, IL1beta, SAT1, OAZ1, DUSP1, S100P, and H3F3A) were measured using qPCR, and two proteomic markers (IL8 and IL1beta) were evaluated by ELISA. RESULTS: Among 7 transcriptomic markers, transcript level of DUSP1 was significantly lower in OSCC patients than in controls and PMOD patients. Between the proteomic markers, the protein concentration of IL8 and IL1beta was significantly higher in OSCC patients than controls and dysplasia patients. Univariate fractional polynomial (FP) models revealed that salivary IL8 protein (IL8p) has the highest AUC value between OSCC patients and controls (0.74) and between OSCC and PMOD patients (0.72). Applying a 2-marker FP model, salivary IL8p combined with IL1beta gave the best AUC value for discrimination between OSCC patients and controls, as well as the IL8p combined with H3F3A mRNA, which gave the best AUC value for discrimination between OSCC and PMOD patients. Multivariate models analysis combining salivary analytes and risk factor exposure related to oral carcinogenesis formed the best combinatory variables for differentiation between OSCC versus PMOL (AUC = 0.80), OSCC versus controls (AUC = 0.87), and PMOD versus controls (AUC = 0.78). CONCLUSIONS: The combination of transcriptomic and proteomic salivary markers is of great value for oral cancer detection and differentiation from PMOD patients and controls. Clin Cancer Res; 22(13); 3340-7. (c)2016 AACR. PMID- 26847065 TI - Collagen binding to OSCAR: the odd couple. AB - In this issue of Blood, Zhou et al reported the high-resolution structure of the collagen-activated osteoclast-associated receptor (OSCAR) bound to a collagen model peptide. Together with binding studies, the results confirm a novel recognition mechanism for collagen by immunoglobulin-like motifs. PMID- 26847066 TI - Does my patient have HIT? There should be an app for that. AB - In this issue of Blood, Nagler et al present a systematic review and meta analysis on the diagnostic accuracy of immunoassays for heparin-induced thrombocytopenia (HIT). Their data, when combined with the 4T score, provide an easy-to-use, evidence-based framework for estimating the probability of HIT PMID- 26847067 TI - Opposite RHOA functions within the ATLL category. AB - In this issue of Blood, Nagata et al reported that different Ras homolog gene family, member A (RHOA) hotspot mutations among the adult T-cell leukemia/lymphoma (ATLL) category have opposite biochemical activities, which are linked to different T-cell phenotypes. PMID- 26847068 TI - A binding relationship with thrombin. AB - In this issue of Blood, Estevez et al propose a model of platelet activation induced by low levels of thrombin and requiring 2 different platelet receptors that demonstrate a mutually dependent cooperativity. PMID- 26847069 TI - HDL/ApoA-I: role in VWF-dependent thrombosis. AB - In this issue of Blood, Chung and colleagues demonstrate in vitro and in an animal model that von Willebrand factor (VWF) self-association under shear stress can be modulated by the high-density lipoprotein and apolipoprotein A-I (HDL/ApoA I) complex, with significant reduction in the length and thickness of VWF fibers. These antiadhesive and antithrombotic properties of HDL/ApoA-I may connect the pathology of microvasculature with that of large vessels (atherosclerosis with arterial thrombosis) and might suggest novel approaches to these thrombotic disorders. PMID- 26847070 TI - Development of an integrated e-health tool for people with, or at high risk of, cardiovascular disease: The Consumer Navigation of Electronic Cardiovascular Tools (CONNECT) web application. AB - BACKGROUND: Cardiovascular disease is the leading killer globally and secondary prevention substantially reduces risk. Uptake of, and adherence to, face-to-face preventive programs is often low. Alternative models of care are exploiting the prominence of technology in daily life to facilitate lifestyle behavior change. OBJECTIVE: To inform the development of a web-based application integrated with the primary care electronic health record, we undertook a collaborative user centered design process to develop a consumer-focused e-health tool for cardiovascular disease risk reduction. METHODS: A four-phase iterative process involved ten multidisciplinary clinicians and academics (primary care physician, nurses and allied health professionals), two design consultants, one graphic designer, three software developers and fourteen proposed end-users. This 18 month process involved, (1) defining the target audience and needs, (2) pilot testing and refinement, (3) software development including validation and testing the algorithm, (4) user acceptance testing and beta testing. From this process, researchers were able to better understand end-user needs and preferences, thereby improving and enriching the increasingly detailed system designs and prototypes for a mobile responsive web application. RESULTS: We reviewed 14 relevant applications/websites and sixteen observational and interventional studies to derive a set of core components and ideal features for the system. These included the need for interactivity, visual appeal, credible health information, virtual rewards, and emotional and physical support. The features identified as essential were: (i) both mobile and web-enabled 'apps', (ii) an emphasis on medication management, (iii) a strong psychosocial support component. Subsequent workshops (n=6; 2*1.5h) informed the development of functionality and lo-fidelity sketches of application interfaces. These ideas were next tested in consumer focus groups (n=9; 3*1.5h). Specifications for the application were refined from this feedback and a graphic designer iteratively developed the interface. Concurrently, the electronic health record was linked to the consumer portal. A written description of the final algorithms for all decisions and outputs was provided to software programmers. These algorithmic outputs to the app were first validated against those obtained from an independently programmed version in STATA 11. User acceptance testing (n=5, 2*1.0h) and beta testing revealed technical bugs and interface concerns across commonly-used web browsers and smartphones. These were resolved and re-tested until functionality was optimized. CONCLUSION: End-users of a cardiovascular disease prevention program have complex needs. A user-centered design approach aided the integration of these needs into the concept, specifications, development and refinement of a responsive web application for risk factor reduction and disease prevention. PMID- 26847071 TI - Role of oral Minocycline in acute encephalitis syndrome in India - a randomized controlled trial. AB - BACKGROUND: Acute encephalitis syndrome (AES) is a public health problem in India. Neuroinfections are believed to be the most important etiology. Minocycline is a semisythetic tetracycline having excellent penetration into cerebrospinal fluid, established neuroprotective and antiviral properties besides action on nonviral causes of AES. It has been shown to be effective in animal model of Japanese encephalitis (JE). A randomized, controlled trial of nasogastric/oral minocycline in JE and AES at a single centre in Uttar Pradesh, northern India, was therefore conducted. METHODS: Patients beyond 3 years of age but excluding women aged 16-44 years - hospitalized with AES of < =7 days duration were enrolled and block randomized to receive nasogastric/oral minocycline or placebo suspension and followed up. Patients, study personnel and those entering data were blinded as to drug or placebo received. Primary outcome was cumulative mortality at 3 months from hospitalization. Analysis was by intention to treat. RESULTS: 281 patients were enrolled, 140 received drug and 141 placebo. While there was no overall statistically significant difference in 3 month mortality between drug and placebo groups [RR = 0 . 83 (0 . 6-1 . 1)], there were encouraging trends in patients older than 12 years [RR = 0.70 (0.41 1.18)] and in Glasgow Outcome Score (GOS) at 3 months (chi(2) = 7 . 44, p = 0 . 059). These trends were further accentuated if patients dying within one day of reaching hospital were excluded [OR for 3 month mortality =0 . 70 (0 . 46-1 . 07), p = 0.090; 3 month GOS p = 0 . 028]. CONCLUSIONS: A trend towards better outcomes was observed with minocycline, especially in those patients who survived the initial day in hospital. These findings should form the basis for planning a larger study and possibly including minocycline in the initial management of AES as seen here. TRIAL REGISTRATION: The trial was registered with Clinical Trials Registry of India (CTRI) - CTRI/2010/091/006143. PMID- 26847073 TI - Accelerated graft dysfunction in heart transplant patients with persistent atrioventricular conduction block. AB - AIMS: Bradyarrhythmia following heart transplantation is common-~7.5-24% of patients require permanent pacemaker (PPM) implantation. While overall mortality is similar to their non-paced counterparts, the effects of chronic right ventricular pacing (CRVP) in heart transplant patients have not been studied. We aim to examine the effects of CRVP on heart failure and mortality in heart transplant patients. METHODS AND RESULTS: Records of heart transplant recipients requiring PPM at St Vincent's Hospital, Sydney, Australia between January 1990 and January 2015 were examined. Patient's without a right ventricular (RV) pacing lead or a follow-up time of <1 year were excluded. Patients with pre-existing abnormal left ventricular function (<50%) were analysed separately. Patients were grouped by pacing dependence (100% pacing dependent vs. non-pacing dependent). The primary endpoint was clinical or echocardiographic heart failure (<35%) in the first 5 years post-PPM. Thirty-three of 709 heart transplant recipients were studied. Two patients had complete RV pacing dependence, and the remaining 31 patients had varying degrees of pacing requirement, with an underlying ventricular escape rhythm. The primary endpoint occurred significantly more in the pacing-dependent group; 2 (100%) compared with 2 (6%) of the non pacing dependent group (P < 0.0001 by log-rank analysis, HR = 24.58). Non-pacing dependent patients had reversible causes for heart failure, unrelated to pacing. In comparison, there was no other cause of heart failure in the pacing-dependent group. CONCLUSIONS: Permanent atrioventricular block is rare in the heart transplant population. We have demonstrated CRVP as a potential cause of accelerated graft failure in pacing-dependent heart transplant patients. PMID- 26847072 TI - Leptin levels in patients with anorexia nervosa following day/inpatient treatment do not predict weight 1 year post-referral. AB - Elevated serum leptin levels following rapid therapeutically induced weight gain in anorexia nervosa (AN) patients are discussed as a potential biomarker for renewed weight loss as a result of leptin-related suppression of appetite and increased energy expenditure. This study aims to analyze the predictive value of leptin levels at discharge as well as the average rate of weight gain during inpatient or day patient treatment for body weight at 1-year follow-up. 121 patients were recruited from the longitudinal Anorexia Nervosa Day patient versus Inpatient (ANDI) trial. Serum leptin levels were analyzed at referral and discharge. A multiple linear regression analysis to predict age-adjusted body mass index (BMI-SDS) at 1-year follow-up was performed. Leptin levels, the average rate of weight gain, premorbid BMI-SDS, BMI-SDS at referral, age and illness duration were included as independent variables. Neither leptin levels at discharge nor rate of weight gain significantly predicted BMI-SDS at 1-year follow-up explaining only 1.8 and 0.4 % of the variance, respectively. According to our results, leptin levels at discharge and average rate of weight gain did not exhibit any value in predicting weight at 1-year follow-up in our longitudinal observation study of adolescent patients with AN. Thus, research should focus on other potential factors to predict weight at follow-up. As elevated leptin levels and average rate of weight gain did not pose a risk for reduced weight, we found no evidence for the beneficial effect of slow refeeding in patients with acute AN. PMID- 26847074 TI - Smart-watches: a potential challenger to the implantable loop recorder? AB - The newest generation of smart-watches offer heart rate monitoring technology via photoplethysmography, a technology shown to demonstrate impressive ability in diagnosing arrhythmias including atrial fibrillation. Combining such technology with the portability, connectivity and other location and activity tracking features smart-watches could represent a powerful new tool in extended non invasive arrhythmia detection. The technology itself, including potential uses and limitations, is discussed. There is a need for further software development but crucially, further work into clarifying the diagnostic accuracy of such technology. PMID- 26847075 TI - Incidence and predictors of clinically relevant cardiac perforation associated with systematic implantation of active-fixation pacing and defibrillation leads: a single-centre experience with over 3800 implanted leads. AB - AIMS: Active-fixation leads have been associated with higher incidence of cardiac perforation. Large series specifically evaluating this complication are lacking. We sought to evaluate the incidence and predictors of clinically relevant cardiac perforation in a consecutive series of patients implanted with active-fixation pacing and defibrillation leads. METHODS AND RESULTS: We conducted a retrospective observational study including all consecutive patients implanted with an active-fixation pacing/defibrillation lead at our institution from July 2008 to July 2015. The incidence of clinically relevant cardiac perforation and cardiac tamponade was evaluated. Univariate and multivariate analyses were used to identify predictors of cardiac perforation. Acute and long-term management of these patients was also investigated. A total of 3822 active-fixation pacing (n = 3035) and defibrillation (n = 787) leads were implanted in 2200 patients. Seventeen patients (0.8%) had clinically relevant cardiac perforation (13 acute and 4 subacute perforations), and 13 (0.5%) had cardiac tamponade resolved with pericardiocentesis. None of the patients with cardiac perforation required surgical treatment. In multivariate analysis, an age >80 years (OR 3.84, 95% CI 1.14-12.87, P = 0.029), female sex (OR 3.14, 95% CI 1.07-9.22, P = 0.037), and an apical position of the right ventricular lead (OR 3.37, 95% CI 1.17-9.67, P = 0.024) were independent predictors of cardiac perforation. CONCLUSIONS: Implantation of active-fixation leads is associated with a low incidence of clinically relevant cardiac perforation. Older and female patients have a higher risk of perforation as well as those patients receiving the ventricular lead in an apical position. PMID- 26847077 TI - Inappropriate high-rate pacing with maximal output due to runaway pacemaker malfunction in a temporary device. PMID- 26847076 TI - Battery drain in daily practice and medium-term projections on longevity of cardioverter-defibrillators: an analysis from a remote monitoring database. AB - AIMS: The longevity of generators is a crucial determinant of the cost effectiveness of therapy with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-D). We evaluated the trend of device-measured residual battery capacity and longevity projections over 5 year follow-up. We also investigated possible factors associated with battery drain. METHODS AND RESULTS: Data from 4851 patients in the European LATITUDE((r)) database who were followed up for a minimum of 3 years were analysed. The factors associated with battery drain (i.e. year-to-year decrease in residual battery capacity), and thus potentially impacting on device longevity, were mainly the pacing parameters in CRT-D devices and the number of shocks delivered and diverted in both ICD and CRT-D (all P < 0.01 on linear regression analysis). Over the first 5 years, the longevity estimates provided by devices showed low intra patient variability and increased with time. The estimates exceeded 10 years for CRT-D and 13 and 12 years for single- and dual-chamber ICDs, respectively. In CRT D patients, the expected patient age on replacement was 80 +/- 12 years, and the expected probability of undergoing device replacement was 63 +/- 13% for New York Heart Association (NYHA) II patients and 37 +/- 16% for NYHA III patients. For comparison, the probabilities of replacing a CRT-D lasting 5 years were 78 +/- 8 and 59 +/- 13%, respectively (both P < 0.001). CONCLUSION: Battery drain was mainly associated with pacing output in CRT-D devices and with the number of capacitor charges in both ICD and CRT-D devices. The longevity estimates provided by the devices were consistent and conservative. According to these estimates, among CRT-D recipients a low proportion of patients should require device replacement. PMID- 26847079 TI - Failure to shock due to misdiagnosis of polymorphic ventricular tachycardia: to bin or not to bin? PMID- 26847078 TI - Serum 25-hydroxyvitamin D and the incidence of atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study. AB - AIMS: To assess the prospective association between circulating 25-hydroxyvitamin D [25(OH)D] and atrial fibrillation (AF) risk. METHODS AND RESULTS: We studied 12 303 participants from the Atherosclerosis Risk in Communities study without baseline AF (1990-92). Baseline serum total 25(OH)D was measured using mass spectrometry. Incident AF cases were identified from electrocardiograms, hospital discharge codes, and death certificates through 2012. We estimated hazard ratios (HRs) and 95% confidence intervals (95% CIs) of AF across clinical categories of serum 25(OH)D concentrations with multivariable Cox models, and tested interactions by age, race, and sex. We meta-analysed our results with those from published prospective studies that reported associations between 25(OH)D and AF risk. During a median follow-up of 21 years, we identified 1866 AF events. In multivariable models, deficient 25(OH)D status (<20 ng/mL), compared with optimal levels (>=30 ng/mL), was not associated with AF risk (HR, 95% CI: 1.10, 0.96 1.26). A significant interaction of 25(OH)D concentrations with age (P = 0.01), but not with race or sex (P > 0.40), was identified, with higher risk of AF among those with deficient 25(OH)D status in younger (HR, 95% CI: 1.35, 1.05-1.73) but not older individuals (HR, 95% CI: 1.02, 0.86-1.21). A meta-analysis of these results and four prospective studies did not support a clinically relevant association of circulating 25(OH)D with AF risk [pooled HR, 95%CI: 1.04, 1.00 1.08, per 1 SD lower 25(OH)D]. CONCLUSION: Low serum 25(OH)D was not associated with incident AF in a community-based cohort and in a meta-analysis of prospective studies. A possible association in younger individuals warrants further investigation. PMID- 26847080 TI - Effect of root canal treatment procedures with a novel rotary nickel titanium instrument (TRUShape) on stress in mandibular molars: a comparative finite element analysis. AB - The aim of this study was to investigate and compare, via finite element analysis (FEA), the effects of endodontic access and canal preparation on stress distribution under functional loading of a mandibular molar treated with novel (TRUShape) and conventional (Vortex) rotary root canal preparation instruments. Identical plastic mandibular molars with natural anatomy had all 4 canals shaped with either TRUShape or a conventional rotary, Vortex (#20 and #30, both by Dentsply Tulsa Dental). Finite element analysis was used to evaluate stress distribution in untreated and treated models. Micro-computed tomography (MCT) of the extracted teeth shaped in vitro was used to inform the FEA model regarding the geometry of root canals and external surfaces. Modeling the intact periodontal support and cancellous/cortical bone was based on anatomical data. Profiles of average and maximum von Mises stresses in dentin of the four treated conditions under functional loading were compared to the untreated model. This comparison was performed for each tooth model with and without root canal obturation and composite restoration. On average, the dentin sections with the most changes after preparation were located in the access cavity, with average stress increase up to +5.7, +8.5, +8.9, and +10.2 % for the TRUShape #20, Vortex #20, TRUShape #30 and Vortex #30, respectively, relative to the untreated model. Within the root canal system, the average stress differences were smaller than <5 % with lower values for TRUShape preparation. A reduction of the average stress in the access cavity was observed as an effect of the composite restoration, while about the same von Mises stress' profiles were found into the root canal. In this finite element analysis, preparation of the access cavity resulted in increased von Mises stresses under functional occlusal load. The limited (up to 0.7 %) retained radicular dentin in the TRUShape versus the Vortex cavity proved effective in reducing masticatory stresses. The bonded restoration modeled in this study only partially counterbalance the combined effects of access cavity and root canal preparation. PMID- 26847081 TI - [Pain-related parental behavior : Maternal and paternal responses to chronic pain of their child and modifications following inpatient interdisciplinary pain treatment]. AB - BACKGROUND: There is a dearth of research studies regarding the pain-related behavior of parents with children suffering from chronic pain. This study examined the pain-related reactions of mothers and fathers, analyzed changes in these reactions following the child's inpatient interdisciplinary pain treatment and identified predictors for these changes. METHOD: Using validated questionnaires 40 mothers and 40 fathers of children suffering from chronic pain reported their pain-related responses and cognitive distortions at treatment commencement, immediately following therapy as well as at follow-up after 6 and 12 months. RESULTS: At treatment commencement there were neither differences between maternal and paternal behavior nor in their reactions towards the sons and daughters. Immediately after treatment both parents showed increased distracting behavior and decreased solicitous behavior. Only the change in solicitous behavior showed long-term stability. The study identified the extent of parental catastrophizing at treatment commencement as well as changes in this reaction during treatment as predictors for reduction in solicitous behavior. The more parents reported catastrophizing thoughts at treatment commencement, the less they changed their solicitous behavior and strong changes in catastrophizing during treatment correlated with strong changes in solicitous reactions. CONCLUSION: Pain-related solicitous behavior can be modified by the interdisciplinary inpatient treatment of chronic pain in children and changes in solicitous behavior seem to be closely related to parental catastrophizing. This association should be considered when dealing with parents of children with chronic pain and also within the framework of future research projects. PMID- 26847083 TI - Cardiac surgery for children with trisomies 13 and 18: Where are we now? AB - The objective is to examine whether cardiac surgery should be considered for children with trisomy 13 or 18 (T13 or 18).T13 or 18 were previously referred to as "lethal" conditions due to high mortality rates and severe disability among survivors. In the last decade, investigations have revealed these conditions are heterogeneous, with increasing numbers of studies describing interventions for these children. A number of factors makes the interpretation of reported outcomes after cardiac surgery challenging: (1) dissimilarities in practice lead to a wide variation in reported outcomes after cardiac surgery; (2) cardiac surgery is generally offered to older, healthier children; (3) cardiac surgeries of widely varying risks are often lumped together in individual studies, and (4) cases where cardiac surgery has been withheld are generally not included in publications. It is unclear whether withholding cardiac surgery for some children with a ventricular septal defect will lead to death, or the development of pulmonary hypertension, or if death will occur from other causes. In this article, we describe two children with different clinical situations and examine whether cardiac surgery would benefit them and how to communicate with their families. Cardiac surgery may be beneficial to some children with trisomy 13 or 18, but may harm others. Every child should be approached in an individual fashion and the goals of each family should be addressed. Children who are more likely to benefit from surgery may be older, healthier children without respiratory support. Rigorous and transparent research is needed to identify factors that affect survival in trisomy 13 or 18. PMID- 26847084 TI - Partitioning the contributions of alternative malaria vector species. AB - BACKGROUND: In many locations malaria is transmitted by more than one vector species. Some vector control interventions, in particular those using genetic approaches, are likely to be targeted against a single species or species complex, at least initially, and it would therefore be useful to be able to predict the epidemiological impact of controlling a single species when multiple vector species are present. METHODS: To address this issue, the classical Ross McDonald model of malaria epidemiology is expanded to account for multiple vector species, giving expressions for the equilibrium prevalence, sporozoite rates and reproductive number. These allow one to predict when control of just one vector species will lead to elimination of the disease. Application of the model is illustrated using published data from a particularly extensive entomological and epidemiological survey before the rollout of bed nets in eastern Kenya, where Anopheles gambiae s.l. and An. funestus were vectors. RESULTS: Meta-analysis indicates that sporozoite rates were 38 % higher in An. gambiae s.l. than in An. funestus, and, according to the model, this difference could be due to An. gambiae s.l. having a higher frequency of feeding on humans, a higher human-to mosquito transmission rate, a lower adult mortality rate, and/or a shorter incubation period. Further calculations suggest that An. gambiae s.l. would have been sufficient to maintain transmission by itself throughout the region, whereas An. funestus would not have been able to support transmission by itself in Malindi District. CONCLUSIONS: Partitioning the contributions of different vector species may allow us to predict whether malaria will persist after targeted vector control. PMID- 26847082 TI - Establishment and characterization of a metastasis model of human gastric cancer in nude mice. AB - BACKGROUND: A mouse model of metastasis of human gastric cancer is one of the most important tools for studying the biological mechanisms underlying human gastric cancer metastasis. In this paper, we established a mouse model of metastatic human gastric cancer in nude mice that has a higher rate of tumor formation and metastasis than existing models. METHODS: To generate the mouse model of metastatic human gastric cancer, fresh tumor tissues from patients that have undergone surgery for gastric cancer were subcutaneously implanted in the right and left groins of nude mice. When the implanted tissue grew to 1 cubic centimeter, the mice were killed, and the tumor tissues were examined and resected. The tumor tissues were implanted into nude mice and subjected to pathological examination, immunohistochemical staining, and real-time PCR for cytokeratin 8/18 (CK8/18), E-cadherin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). The mice were also analyzed for metastasis in their peritoneum, abdominal cavity, and internal organs by histopathological examination. Tissues collected from these organs were examined for pathology. RESULTS: After ten generations of implantation, all mice developed tumor growth at the implanted position, 94% of the mice developed metastasis to the retroperitoneum and viscera. The implanted and metastatic tumor maintained the same histological features across all generations, and metastasis was observed in the esophagus, stomach, spleen, liver, kidney, adrenal, intestine, and pancreas. These metastatic tumors revealed no detectable expression of CK8/18, E-cadherin, VCAM-1, and ICAM-1. CONCLUSIONS: This model will serve as valuable tool for understanding the metastatic process of human gastric cancer. PMID- 26847085 TI - Suppression of c-FLIPL promotes JNK activation in malignant melanoma cells. AB - The up-regulation of cellular Fas-associated death domain-like interleukin-1beta converting enzyme (FLICE)-like inhibitory protein (c-FLIP) has been reported in various tumor types, and has been previously shown to be associated with the clinicopathological features of melanoma. To assess its potential role in cancer therapy, the present study evaluated the effects of short hairpin (sh)RNAs of different c-FLIP isoforms on cellular proliferation and c-Jun N-terminal kinase (JNK) signaling. Human c-FLIP shRNA plasmids were constructed and transfected into the A875 melanoma cell line. It was observed that c-FLIP shRNA exhibited strong inhibitory effects against the levels of phosphorylated-JNK and inhibited cellular proliferation in A875 cells. Thus, this indicated that c-FLIP long form shRNA serves a specific inhibitory role in cellular proliferation through inducing the activation of the JNK pathway in A875 cells. The present study provided insight into the development of RNAi based therapies for melanoma. PMID- 26847086 TI - Diagnostically important muscle pathology in DNAJB6 mutated LGMD1D. AB - INTRODUCTION: Limb girdle muscular dystrophies are a large group of both dominantly and recessively inherited muscle diseases. LGMD1D is caused by mutated DNAJB6 and the molecular pathogenesis is mediated by defective chaperonal function leading to impaired handling of misfolded proteins which normally would be degraded. Here we aim to clarify muscle pathology of LGMD1D in order to facilitate diagnostic accuracy. After following six Finnish LGMD1D families, we analysed 21 muscle biopsies obtained from 15 patients at different time points after the onset of symptoms. All biopsies were obtained from the lower limb muscles and processed for routine histochemistry, extensive immunohistochemistry and electron microscopy. RESULTS: Histopathological findings were myopathic or dystrophic combined with rimmed vacuolar pathology, and small myofibrillar aggregates. These myofibrillar inclusions contained abnormal accumulation of a number of proteins such as myotilin, alphaB-crystallin and desmin on immunohistochemistry, and showed extensive myofibrillar disorganization with excess of Z-disk material on ultrastructure. Later in the disease process the rimmed vacuolar pathology dominated with rare cases of pronounced larger pleomorphic myofibrillar aggregates. The rimmed vacuoles were reactive for several markers of defect autophagy such as ubiquitin, TDP-43, p62 and SMI-31. CONCLUSIONS: Since DNAJB6 is known to interact with members of the chaperone assisted selective autophagy complex (CASA), including BAG3 - a known myofibrillar myopathy causing gene, the molecular muscle pathology is apparently mediated through impaired functions of CASA and possibly other complexes needed for the maintenance of the Z-disk and sarcomeric structures. The corresponding findings on histopathology offer clues for the diagnosis. PMID- 26847087 TI - Analysis of the expression and localization of tight junction transmembrane proteins, claudin-1, -4, -7, occludin and JAM-A, in human cervical adenocarcinoma. AB - OBJECTIVE: Tight junction proteins have recently been reported to be useful for distinguishing between neoplastic and non-neoplastic tissues. In this study, we evaluated the expression and localization of tight junction transmembrane proteins in human cervical adenocarcinoma and adenocarcinoma in situ (AIS), and we determined whether their expression patterns could distinguish cervical adenocarcinoma from non-neoplastic cervical glands. METHODS: Fifty-five patients with cervical adenocarcinoma or AIS were included in this study. Surgical specimens were immunohistochemically stained for claudin (CLDN) -1, -4, -7, occludin, and JAM-A. RESULTS: Significantly higher expression levels of CLDNs and JAM-A were found in cervical AIS and adenocarcinoma than in non-neoplastic glands. In cervical AIS and adenocarcinoma, localization of CLDN1 and JAM-A was extended throughout the whole cell membranes, whereas they were predominantly expressed at the most apical cell-cell junction in non-neoplastic glands. ROC curve analysis revealed that immunoreactivities of CLDN-1 or JAM-A successfully distinguished neoplasms from non-neoplastic cervical glands with high specificity (CLDN-1, 79.1%; JAM-A, 79.1%) and high sensitivity (CLDN-1, 84.1%; JAM-A, 95.5%). CONCLUSIONS: As expected, there were immunohistochemical differences between cervical adenocarcinoma and non-neoplastic cervical glands by using antibodies against tight junction transmembrane proteins. These results suggest that CLDN-1 and JAM-A are potential biomarkers for cervical adenocarcinoma. PMID- 26847088 TI - The association of birth weight and postnatal growth with energy intake and eating behavior at 5 years of age - a birth cohort study. AB - BACKGROUND: Low and high birth weight and accelerated postnatal weight gain are associated with an increased risk of obesity. Perinatal effects on energy intake and eating behavior have been proposed as underlying mechanisms. This study aimed to examine the independent associations of birth weight and postnatal weight and height gain with childhood energy intake and satiety response. METHODS: In a birth cohort study, we used data from 2227 children (52% male), mean age 5.6 (+/ 0.4) years. Mean daily energy intake and satiety response were parent-reported through validated questionnaires. Exposures were birth weight z-score and conditional weight and height gain between 0-1, 1-3, 3-6, 6-12 months and 12 months to 5 years. Conditional weight and height are residuals of current weight and height regressed on prior growth data, to represent deviations from expected growth. Analyses were adjusted for a set of potential confounding variables. RESULTS: Conditional weight gain between 1-3, 3-6 months and 12 months to 5 years was significantly associated with energy intake, with 29.7 (95%-CI: 4.6; 54.8), 24.0 (1.8; 46.1) and 79.5 (29.4; 129.7) kcal/day more intake for each Z-score conditional weight gain between 1-3, 3-6 months and 12 months to 5 years, respectively. Conditional height gain between 0-1, 1-3 months and 12 months to 5 years was negatively associated with energy intake (beta: -42.0 [66.6; -17.4] for 0-1 months, -35.1 [-58.4; -11.8] for 1-3 months and -37.4 [-72.4; -2.3] for 12 months to 5 years). Conditional weight gain in all periods was negatively associated with satiety response, with effect sizes from - 0.03 (-0.06; -0.002) in early infancy to -0.12 (-0.19; -0.06) in childhood. Birth weight was not associated with energy intake or satiety response. CONCLUSIONS: Our findings suggest that accelerated infant and childhood weight gain are associated with increased energy intake and diminished satiety response at 5 years. Accelerated height gain seems to be beneficial for childhood energy intake. This perinatal 'programming' of energy intake and eating behavior provide a potential mechanism linking early life influences with later obesity and cardiovascular disease. PMID- 26847090 TI - Tumefactive Demyelinating Lesions in Multiple Sclerosis and Associated Disorders. AB - Tumefactive demyelinating lesions are rare consequences of central nervous system (CNS) idiopathic inflammatory demyelinating diseases. Tumefactive demyelinating lesions pose a diagnostic challenge because they can mimic tumors and abscesses and because they can be caused by a heterogeneous range of disorders. This article reviews the recent literature on the clinical presentation; radiographic features; prognosis; and management of tumefactive demyelinating lesions in multiple sclerosis, acute demyelinating encephalomyelitis, neuromyelitis optica, and the rare variants of multiple sclerosis including Schilder's disease, Marburg acute multiple sclerosis, and Balo's concentric sclerosis. PMID- 26847091 TI - Photostimulation by femtosecond laser triggers restorable fragmentation in single mitochondrion. AB - Mitochondrial research is important to the study of ageing, apoptosis, and metabolic diseases. Over the years, mitochondria have been studied with stimulation by chemical agents in a global manner for basic and applied research. This approach lacks of precision and accuracy in terms of spatial and temporal resolution. Here we demonstrate a direct and well-defined photostimulation targeting on single mitochondrial tubular structure using a tightly-focused femtosecond (fs) laser that could precisely activate mitochondria at single tubule level to show restorable fragmentation and subsequent recovery after tens of seconds. In these two processes, a series of mitochondrial reactive oxygen species (mROS) flashes was observed and found critical to the mitochondrial fragmentation. Meanwhile, transient openings of mitochondrial permeability transition pores (mPTP) were seen with oscillations of mitochondrial membrane potential. These activities were crucial for the recovery through scavenging the mROS. Without the feedback mechanisms, the fragmented mitochondria could not return back to their original tubular structure. These interesting observations show that photostimulation by fs laser is an active, precise, clean and well defined approach to dissect the role of mitochondria in normal physiology and different kinds of diseases. PMID- 26847089 TI - Intensity modulated radiation therapy (IMRT) for sinonasal tumors: a single center long-term clinical analysis. AB - BACKGROUND: Radiotherapy has a central role in the treatment of sinonasal malignancies, either as postoperative or as primary therapy. To study the efficacy and safety of intensity modulated radiotherapy (IMRT) for sinonasal tumors a single center retrospective evaluation focusing on survival and therapy related toxicity was performed. METHODS: One hundred twenty two patients with primary (n = 82) or recurrent (n = 40) malignant sinonasal tumors were treated with intensity modulated radiotherapy between 1999 and 2009 at the University Clinic of Heidelberg and the German Cancer Research Center and retrospectively analyzed. Most patients had adenoid cystic carcinomas (n = 47) or squamous cell carcinoma (n = 26). 99 patients received postoperative radiotherapy. The median total dose was 64 Gy in conventional fractionation (1.8-2 Gy). Overall survival (OS), progression free survival (PFS) and local recurrence free survival (LRFS) rates were calculated using the Kaplan-Meier method. The log-rank test and Fishers Exact test were applied for univariate analysis, Cox-regression was used for multivariate analysis. RESULTS: Median follow up was 36 months. 1-, 3- and 5 year estimated overall survival rates were 90, 70 and 54 % respectively. Median progression free survival and local recurrence free survival was 45 and 63 months respectively. Progression free survival and local recurrence free survival at 1, 3 and 5 years were 76, 57 and 47, and 79, 60 and 51 % respectively. 19 patients (15.5 %) were diagnosed with distant metastases. Univariate analysis revealed significantly improved OS and LRFS for treatment of tumors after primary diagnosis, first series of irradiation and radiation dose >=60 Gy. Multivariate analysis revealed only treatment in primary situation as an independent prognostic factor for OS and LRFS. Acute CTC grade III mucositis was seen in 5 patients (4.1 %) and CTC grade II dysgeusia in 19 patients (15.6 %). Dysgeusia, dysosmia and ocular toxicity were the most common late adverse events. CONCLUSIONS: Our data support the results of previous studies and indicate that intensity modulated radiation therapy (IMRT) represents an effective and safe treatment approach for patients with sinonasal carcinomas. PMID- 26847093 TI - Infliximab or biosimilars in sarcoidosis; to switch or not to switch? PMID- 26847092 TI - Reversible acetylation on Lys501 regulates the activity of RNase II. AB - RNase II, a 3' to 5' processive exoribonuclease, is the major hydrolytic enzyme in Escherichia coli accounting for ~90% of the total activity. Despite its importance, little is actually known about regulation of this enzyme. We show here that one residue, Lys501, is acetylated in RNase II. This modification, reversibly controlled by the acetyltransferase Pka, and the deacetylase CobB, affects binding of the substrate and thus decreases the catalytic activity of RNase II. As a consequence, the steady-state level of target RNAs of RNase II may be altered in the cells. We also find that under conditions of slowed growth, the acetylation level of RNase II is elevated and the activity of RNase II decreases, emphasizing the importance of this regulatory process. These findings indicate that acetylation can regulate the activity of a bacterial ribonuclease. PMID- 26847094 TI - Angiotensin converting enzyme I/D polymorphism and sarcoidosis risk. AB - BACKGROUND: This meta-analysis investigates the associations of angiotensin converting enzyme (ACE) polymorphism and risk of sarcoidosis. MATERIAL AND METHOD: Two reviewers independently searched three databases including PubMed, EMBASE, and Cochrane database to identify published studies. Full texts of the selected studies were accessed and related data was extracted using a standardized data extraction form. RESULTS: A total of 18 studies contained a total of 1626 patients with sarcoidosis in case group and 2465 healthy controls in control group. Results of the current meta-analysis revealed that ACE DD genotype was associated with a significantly increased risk of sarcoidosis (OR=1.21; 95% CI, 1.06-1.38; I2=48%). In the race subgroup analysis, Asians with ACE DD genotype showed no significant increased risk of sarcoidosis (OR=1.37; 95% CI, 0.94-1.99; I2=78%). Caucasians with ACE DD genotype had an increased sarcoidosis risk (OR=1.16; 95% CI, 1.01-1.36; I2=24%). CONCLUSIONS: Our meta analysis indicated that the ACE DD genotype correlated with an increased risk of sarcoidosis. PMID- 26847095 TI - Infliximab for chronic cutaneous sarcoidosis: a subset analysis from a double blind randomized clinical trial. AB - BACKGROUND: Limited evidence exists demonstrating an effective treatment for chronic cutaneous sarcoidosis. OBJECTIVE: To determine infliximab's effectiveness in sarcoidosis. METHODS: We conducted a subset analysis from a randomized, double blind, placebo-controlled trial for chronic pulmonary sarcoidosis to determine infliximab's effectiveness. Patients with chronic cutaneous sarcoidosis received infliximab (3 or 5 mg/kg) or placebo over 24 weeks. Of 138 patients, the subset analysis evaluated 17 patients with chronic facial and another 9 patients with nonfacial skin involvement. The SASI evaluated lesions for degree of erythema, desquamation, induration, and percentage of area involved. Facial and nonfacial lesions were scored in a blinded manner. RESULTS: Among 5 placebo-treated and 12 infliximab-treated patients, an improvement was observed with infliximab versus placebo in change from baseline to weeks 12 and 24 in desquamation (P<0.005) and induration (P<0.01) at week 24. Erythema, percentage of area involved and the evaluation of paired photographs did not reveal significant differences. LIMITATIONS: Sample size; more extensive disease in placebo patients; chronic therapy upon enrollment; lung as primary organ of sarcoidosis involvement; limited investigator experience with SASI. CONCLUSIONS: Infliximab appears to be a beneficial treatment for chronic cutaneous sarcoidosis. The SASI scoring system demonstrated significant improvement versus placebo in lesion desquamation and induration. PMID- 26847097 TI - Comparison of the diagnostic value of different lymphocyte subpopulations in bronchoalveolar lavage fluid in patients with biopsy proven sarcoidosis. AB - BACKGROUND: Bronchoalveolar lavage is considered a helpful tool in the diagnosis of diffuse parenchimal lung diseases such as sarcoidosis. CD4/CD8 ratio is higly specific but not sensitive to distinguish sarcoidosis and other intestitial lung diseases. We aimed to compare the diagnostic value of CD4/CD8 ratio and other lmphocyte subpopulations such as CD3+16+56, CD103+, CD4+CD103+, CD8+CD103+ in bronchoalveolar lavage to distinguish sarcoidosis and other nonsarcoidosis interstitial lung diseases. METHODS: Using the bronchoscopy records from 2006 to 2013, we evaluated 68 patients with biopsy proven sarcoidosis and 72 patients with clinicoradiological and/or biopsy proven diffuse parenchimal lung diseases. Cut off values, sensitivity and specificity were given for aforementioned parameters. RESULTS: Bronchoalveolar lavage CD4/CD8 ratio, CD4+ T lymphocyte percentage, CD4+103+, CD3+CD103-, CD8+CD103+/CD103+ ratio were significantly higher in sarcoidosis than other diffuse parenchimal lung diseases whereas CD3+103+, CD3+16+56+, CD8+, CD8+CD103+, CD8+CD103+/CD8+ were significantly lower. Best cut off value of CD4/CD8 was 1.34 with sensitivity and specificity 76.4%, 79.4% respectively. The cut off values of CD4/CD8 of >3.5 and >2.5 had specificity 95.9% and 95.3%, respectively and sensitivity 52%, 41%, respectively. CONCLUSION: CD4/CD8 ratio is highly specific but not sensitive for sarcoidosis diagnosis. Thus, BAL flow cytometry is not diagnostic alone without appropriate clinicoradiological and/or histopathological findings. PMID- 26847096 TI - Rituximab for the treatment of connective tissue disease-associated interstitial lung disease. AB - OBJECTIVE: To describe our experience with rituximab (RTX) as treatment for a diverse spectrum of chronic connective tissue disease-associated interstitial lung disease (CTD-ILD). METHODS: Twenty-four subjects with CTD-ILD were included. All had pulmonary function testing before and after their first RTX infusion. Each subject was evaluated in a multidisciplinary autoimmune and ILD outpatient clinic. Data were extracted by retrospective review of complete medical records. RESULTS: Most subjects were middle-aged white women with rheumatoid arthritis (RA) (n=15) and a nonspecific interstitial pneumonia (NSIP) pattern on high resolution chest computed tomography scans (n=17). Sixteen subjects received a corticosteroid-sparing agent at the time of RTX initiation; mostly mycophenolate mofetil (n=8). RTX administration was not associated with corticosteroid-sparing effects: 13 subjects were on prednisone at the time of the initial RTX cycle, and 9 remained on prednisone at 6 months after (mean daily dosage 10.2+/-16.2 mg before vs. 5.6+/-11.0 mg after, p=0.27). RTX had no appreciable effect on pulmonary physiology; however, individual trajectories for percentage predicted forced vital capacity (FVC%) were highly variable. The underlying CTD (RA vs. non RA) and ILD pattern did not appear to affect response to RTX. Among 14 subjects who received multiple RTX cycles, FVC% trajectories were variable: FVC% increased in eight and declined in six. Respiratory infections were the most common post RTX adverse event. CONCLUSION: In this small, retrospective study of chronic CTD ILD, RTX was not associated with changes in FVC% or corticosteroid-sparing effects. Controlled, prospective studies are needed to more confidently define the effects of RTX in CTD-ILD. PMID- 26847098 TI - Bronchoalveolar lavage chitotriosidase activity as a biomarker of sarcoidosis. AB - BACKGROUND: Chitotriosidase (CTO) was shown to be a good biomarker of sarcoidosis. Increased levels in bronchoalveolar lavage fluid (BALF) were reported and associated with more severe forms of the disease. OBJECTIVES: The aim of the study was to evaluate the value of CTO in BALF as a routine biomarker of sarcoidosis. METHODS: The study included 85 patients in 9 control subjects in whom serum and BALF CTO were measured. RESULTS: Significantly higher CTO levels were detected in BALF of sarcoidosis patients than in control subjects (p < 0.001). There was good correlation between serum and BALF CTO levels in sarcoidosis patients (Spearman's Rho 0.481, p < 0.001). Serum but not BALF CTO had good correlation with clinical parameters. Only in a group of patients with BALF CTO above upper normal range there was association of BALF CTO with impaired FVC (p = 0.020) and chest radiograph score (0-2 vs. 3-4, p = 0.016). CONCLUSIONS: In comparison to serum CTO no additional benefit of determining CTO in BAL for routine sarcoidosis workup was shown. PMID- 26847099 TI - Angiotensin-converting Enzyme as a Predictor of Extrathoracic Involvement of Sarcoidosis. AB - BACKGROUND: Sarcoidosis is a multisystem disease, with extrathoracic involvement occurring in 25-50% of patients. Multi-organ involvement is often associated with a more chronic and severe course. The value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) in diagnosing extrathoracic involvement in sarcoidosis has been demonstrated; however, because of the radiation dose and high cost, indications for its use must be well defined. Angiotensin-converting enzyme (ACE) is produced by active granuloma cells; thus, serum ACE (sACE) levels may reflect the total granuloma load. OBJECTIVES: In this retrospective study, we evaluated the diagnostic value of sACE in the detection of extrathoracic involvement in sarcoidosis. METHODS: 43 patients with biopsy proven sarcoidosis underwent FDG-PET/CT during the initial workup. Positive findings were classified as thoracic and/or extrathoracic. The diagnostic value of sACE was estimated using sensitivity, specificity, and area under the receiver operating characteristic curves (AUCs). RESULTS: Of the 43 patients studied, 17 (39.7%) had extrathoracic involvement. In this group, sACE values were higher than in patients without extrathoracic involvement (331 vs. 150, p=0.002) and correlated positively with extrathoracic involvement (R:0.532 p=0.02). Receiver operator characteristic curve analysis revealed an AUC of 0.816 [95% confidence interval: 0.669-0.963, p=0.002], 70.6% sensitivity and 80% specificity at the sACE cut-off value. CONCLUSIONS: In sarcoidosis, extrathoracic involvement may be life threatening or indicative of poor outcome. sACE levels are easily determined and may predict extrathoracic involvement. In patients with sarcoidosis, sACE levels can be used to better define those who would benefit from FDG-PET/CT examination to detect extrathoracic involvement. PMID- 26847100 TI - Cardiovascular magnetic resonance-guided diagnosis of cardiac affection in a Caucasian sarcoidosis population. AB - BACKGROUND: Clinically evidenced cardiac involvement in systemic sarcoidosis occurs in approximately 5% of patients, whereas post-mortem examinations identify cardiac sarcoidosis in over 60% of cases. OBJECTIVE: Given the inconsistency of diagnostic approaches, we took aim at prospectively investigating the prevalence of cardiac sarcoidosis by cardiovascular magnetic resonance (CMR) in a primary Caucasian population and at correlating the results with standard clinical parameters. METHODS: 188 patients with histologically proven sarcoidosis were included, provenient from the local pneumological department and a national sarcoidosis self-help association. All of them underwent CMR-imaging. Complementary 12-lead ECG, Holter monitoring, laboratory and pulmonary function testing were performed. RESULTS: CMR-based diagnosis of cardiac sarcoidosis was made in 29 patients (15.4%), of whom 17 patients (9% of total cohort) exhibited increased relative gadolinium enhancement - reflecting acute inflammatory processes -, while 11 patients (5.9% of total cohort) showed late gadolinium enhancement as a marker for nonviable tissue damage. Both abnormalities were present in 1 patient (0.5%). Correlation analysis evinced significant association between CMR-diagnosed cardiac sarcoidosis and reduction in LVEF, increase in diastolic interventricular septal thickness, diastolic dysfunction as well as limited electrocardiographic abnormalities. Neither laboratory values nor pulmonary function parameters correlated with presence or activity of cardiac sarcoidosis. CONCLUSIONS: Among our predominantly Caucasian sarcoidosis study population, CMR-detected cardiac affection occurred in 15.4% and was missed by internationally valid standard clinical testing in all but one case. It reinforces CMR's diagnostic value as modality of choice to evaluate cardiac sarcoidosis. The estimation of its prognostic potential and its value in assessing the incidence of cardiac sarcoidosis however requires further longitudinal investigation. PMID- 26847102 TI - Characterization of F-18 Fluorodeoxyglucose PET/CT in Granulomatosis with Polyangiitis. AB - OBJECTIVE: Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease characterized by necrotizing granulomatous inflammation and small vessel vasculitis that primarily involves the upper airways, lungs, and kidneys. F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is an imaging technique that is increasingly used in the evaluation of patients with other types of vasculitis (giant-cell arteritis). We explored the potential utility of FDG-PET/CT in the management of GPA. METHODS: We identified 12 patients with GPA who underwent a total of 26 FDG-PET/CT scans from January 2005 to March 2013. The presenting clinicoradiologic features and FDG-PET/CT scans were analyzed. RESULTS: In all patients the FDGPET/ CT scans were performed to evaluate known or suspected malignancies. Differentiation between inflammatory and malignant lesions could not be achieved based on FDG uptake intensity (maximal SUV). GPA lesions of the respiratory tract and lung were more clearly detected by FDG PET/CT than by CT scan alone. In 3 of the 12 patients occult areas of vascular inflammation were identified that were not previously appreciated on usual organ screening in GPA. In 8 patients the FDG-PET/CT facilitated diagnosis by identifying the best biopsy site. Two patients had follow-up FDG-PET/CT scans which demonstrated decreased FDG uptake after treatment for GPA. CONCLUSIONS: FDG PET/CT cannot differentiate between malignant and inflammatory lesions in GPA. However, occult sites of disease activity may be identified and provide a better assessment of the extent of disease activity and a more accurate assessment of treatment response. PMID- 26847101 TI - The Value of T-SPOT.TB in Early Diagnosis of Tracheobronchial Tuberculosis. AB - OBJECTIVE: To evaluate the value of T-SPOT.TB in the diagnosis of tracheobronchial tuberculosis. METHODS: This study included in January 2010 to October 2014 in the three gorges university during the first clinical medical college of final 283 diagnosed with tracheal bronchus TB patients (including 273 patients with pathological biopsy diagnosis and 10 called suspected TB patients), at the same time will be 283 active TB patients as a parallel control group included in this study. They were all given traditional detection methods acid fast stain and diseased tissue pathological biopsy and the new detection method T SPOT.TB. RESULTS: Sputum smear acid-fast stain sensitivity rate is 39.2% (111/283), typical TB diseased tissue pathology biopsy pathology morphology of 221 cases (78.1%), tend to TB 52 cases (18.4%),while T-SPOT. TB testing sensitivity and speciality rate is 93.6% (265/283) and 85.1% (241/283), which is much higher then the former two. CONCLUSION: T-SPOT.TB can provide important basis for the diagnosis of tracheobronchial tuberculosis.It is the fastest and most accu-rate method in the diagnosis of tracheobronchial tuberculosis. PMID- 26847103 TI - Prognostic value of the initial chest high-resolution CT pattern in idiopathic pulmonary fibrosis. AB - BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial pneumonia with a poor prognosis, and there is a clear need to identify factors predictive of disease progression and survival. Previous studies have suggested that patient survival may be associated with specific features on chest CT. Here, we evaluated the prognostic value of the initial high-resolution CT (HRCT) pattern according to the classification recommended by the most recent guidelines for IPF. METHODS: A total of 66 patients diagnosed with IPF between 2000 and 2010 were included in this retrospective study. Patients were classified into three groups based on the pattern of their initial HRCT: definite usual interstitial pneumonia (UIP) (UIPdef n = 26), possible UIP (UIPposs, n = 29), or inconsistent with UIP (UIPincons n = 11). Epidemiological data, functional data, and patient survival were compared. RESULTS: The median survival time was 30, 46, and 107 months for UIPdef, UIPposs, and UIPincons groups, respectively (p = 0.51). Patients with UIPdef pattern HRCT were more likely to be former smokers (p = 0.007) in comparison with UIPincons, to have a lower diffusing capacity of the lung for carbon monoxide in comparison with UIPposs (p = 0.01) and to have a higher estimated systolic pulmonary artery pressure (p = 0.002). Patients with UIPincons pattern HRCT were more likely to be younger (p = 0.004). CONCLUSION: There were no significant difference in survival between the three patient groups categorized by their initial chest HRCT pattern. PMID- 26847104 TI - IgG4-related lung disease: a case series of 6 patients and review of the literature. AB - IgG4 related disease has been recently proposed as a unifying term for a group of inflammatory conditions previously referred to by a plethora of other names. The common denominator for these entities is the histopathologic finding of lymphocytic infiltrates rich in IgG4 producing plasma cells, often accompanied by storiform fibrosis and obliterative phlebitis. Many medical conditions have been attributed to IgG4-related disease,but few reports of IgG4-related lung disease have been published, and it remains a rare condition about which little is known. In this report, we describe the clinical and pathologic features of six patients with IgG4-related disease of the lung. Patients were followed 1-5 years following their diagnosis. We describe unique features of IgG4-related lung disease, including one patient who presented with alveolar hemorrhage and a positive anti neutrophil cytoplasmic antibody and two patients whose disease improved after treatment with mycophenylate mofetil. Two patients presented with pulmonary pseudotumor. We conclude that the clinical presentation of IgG4-related lung disease varies widely, and histopathology remains the key to diagnosis. PMID- 26847105 TI - A case of acute kidney injury caused by granulomatous tubulointerstitial nephritis associated with sarcoidosis and concomitant presence of anti-glomerular basement membrane antibody. AB - We encountered a case of granulomatous tubulointerstitial nephritis in a patient with sarcoidosis, who was also found to show an elevated serum titer of anti glomerular basement membrane (GBM) antibody. The serum creatinine level had been documented to be within normal range 8 months before the first visit. Gallium scintigraphy revealed bilateral kidney uptake, but no uptake in the pulmonary hilum. No typical findings of sarcoidosis, e.g., bilateral hilar adenopathy, uveitis or elevated serum ACE level were recognized in the early stage. Echocardiography showed basal thinning of the interventricular septum, a specific feature of cardiac sarcoidosis, and hilar lymph node uptake on gallium scintigraphy and anterior uveitis appeared during the disease course. Active tuberculosis, fungal infection, vasculitis and malignancy were clinically excluded. We performed a renal biopsy. Light microscopy revealed non-caseating granulomatous tubulointerstitial nephritis with multinucleated giant cells and normal glomeruli. Inflammatory reaction was seen only within the interstitial tubules. The serum creatinine level had increased to 4.52 mg/dl. The patient was administered methylprednisolone pulse therapy, followed by administration of oral prednisolone. The renal function improved immediately in response to this therapy. Based on the above, we made the final diagnosis of granulomatous tubulointerstitial nephritis associated with sarcoidosis. While the serum titer of anti- GBM antibody was elevated, to our surprise, renal biopsy did not reveal linear anti-GBM antibody staining in this case. Furthermore, interestingly, the serum anti-GBM antibody titer in our patient decreased in parallel with the clinical improvement of sarcoidosis. Severe and progressive renal dysfunction was the most prominent clinical feature without other organ manifestations in our patient, which is a rare occurrence in sarcoidosis. PMID- 26847106 TI - Pulmonary Microscopic Polyangiitis Presenting as Acute Respiratory Failure from Diffuse Alveolar Hemorrhage. AB - Microscopic polyangiitis and granulomatosis with polyangiitis are rare anti neutrophilic cytoplasmic antibody-associated systemic vasculitides that predominantly affect small to medium sized vessels of the lungs and kidneys. These syndromes are largely confined to older adults and often present sub acutely following weeks to months of nonspecific prodromal symptoms. While both diseases often manifest within multiple organ systems concurrently, the disease spectrum of microscopic polyangiitis almost always includes the kidneys, while granulomatosis with polyangiitis is most commonly associated with pulmonary disease. We present two cases of rapid onset respiratory failure secondary to diffuse alveolar hemorrhage in young active duty military personnel. After serological testing and surgical lung biopsy, both patients were diagnosed with microscopic polyangiitis with isolated pulmonary involvement. PMID- 26847107 TI - Conventional bronchoscopy techniques still are as efficient as newer techniques in the diagnosis of sarcoidosis. PMID- 26847109 TI - sciReptor: analysis of single-cell level immunoglobulin repertoires. AB - BACKGROUND: The sequencing of immunoglobulin (Ig) transcripts from single B cells yields essential information about Ig heavy:light chain pairing, which is lost in conventional bulk sequencing experiments. The previously limited throughput of single-cell approaches has recently been overcome by the introduction of multiple next-generation sequencing (NGS)-based platforms. Furthermore, single-cell techniques allow the assignment of additional data types (e.g. cell surface marker expression), which are crucial for biological interpretation. However, the currently available computational tools are not designed to handle single-cell data and do not provide integral solutions for linking of sequence data to other biological data. RESULTS: Here we introduce sciReptor, a flexible toolkit for the processing and analysis of antigen receptor repertoire sequencing data at single cell level. The software combines bioinformatics tools for immunoglobulin sequence annotation with a relational database, where raw data and analysis results are stored and linked. sciReptor supports attribution of additional data categories such as cell surface marker expression or immunological metadata. Furthermore, it comprises a quality control module as well as basic repertoire visualization tools. CONCLUSION: sciReptor is a flexible framework for standardized sequence analysis of antigen receptor repertoires on single-cell level. The relational database allows easy data sharing and downstream analyses as well as immediate comparisons between different data sets. PMID- 26847108 TI - A prospective, single-centre, randomised study evaluating the clinical, imaging and immunological depth of remission achieved by very early versus delayed Etanercept in patients with Rheumatoid Arthritis (VEDERA). AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis, with significant impact on quality of life and functional status. Whilst biologic disease modifying anti-rheumatic drugs (bDMARD) such as tumour necrosis factor inhibitor (TNFi) agents have revolutionised outcomes in RA, early diagnosis with immediate conventional therapy, titrated in a treat to target approach is also associated with high remission rates. The main aim of the VEDERA study (Very Early versus Delayed Etanercept in Rheumatoid Arthritis) is to assess the depth of remission, sustainability of remission and immunological normalisation induced by very early TNFi with etanercept (ETN) or standard of care +/- delayed ETN. METHODS/DESIGN: VEDERA is a pragmatic, phase IV single-centre open-label randomised superiority trial of 120 patients with early, treatment-naive RA. Patients will be randomised 1:1 to first-line ETN and methotrexate (MTX) or MTX with additional synthetic disease modifying anti-rheumatic drugs (sDMARDs) according to a treat to target (TT) protocol with further step up to ETN and MTX after 24 weeks if remission is not achieved. Participants will have regular disease activity assessments and imaging evaluation including musculoskeletal ultrasound and MRI. The main objective of this study is to assess the proportion of patients with early RA that achieve clinical remission at 48 weeks, following either treatment strategy. In addition, the participants are invited to take part in a cardio-vascular sub-study (Coronary Artery Disease in RA, CADERA), which aims to identify the incidence of cardiovascular abnormalities in early RA. DISCUSSION: The hypothesis underlining this study is that very early treatment with first-line ETN increases the proportion of patients with rheumatoid arthritis achieving clinical remission, in comparison to conventional therapy. TRIAL REGISTRATION: NCT02433184 , 23/04/2015. PMID- 26847110 TI - Damage control resuscitation: lessons learned. AB - BACKGROUND: Damage control resuscitation describes an approach to the early care of very seriously injured patients. The aim is to keep the patient alive whilst avoiding interventions and situations that risk worsening their situation by driving the lethal triad of hypothermia, coagulopathy and acidosis or excessively stimulating the immune-inflammatory system. It is critical that the concepts and practicalities of this approach are understood by all those involved in the early management of trauma patients. This review aims to summarise this and discusses current knowledge on the subject. INTERVENTIONS: Damage control resuscitation forms part of an overall approach to patient care rather than a specific intervention and has evolved from damage control surgery. It is characterised by early blood product administration, haemorrhage arrest and restoration of blood volume aiming to rapidly restore physiologic stability. The infusion of large volumes of crystalloid is no longer appropriate, instead the aim is to replace lost blood and avoid dilution and coagulopathy. In specific situations, permissive hypotension may also be of benefit, particularly in patients with severe haemorrhage from an arterial source. As rapid arrest of haemorrhage is so important, team-based protocols that deliver patients rapidly but safely, via CT scan where appropriate, to operating theatres or interventional radiology suites form a critical part of this process. CONCLUSIONS: Given that interventions are so time dependent in the severely injured, it is likely that by further improving trauma systems and protocols, improvements in outcome can still be made. Further research work in this area will allow us to target these approaches more accurately to those patients who can benefit most. PMID- 26847111 TI - Skipping of exon 27 in C3 gene compromises TED domain and results in complete human C3 deficiency. AB - Primary deficiency of complement C3 is rare and usually associated with increased susceptibility to bacterial infections. In this work, we investigated the molecular basis of complete C3 deficiency in a Brazilian 9-year old female patient with a family history of consanguinity. Hemolytic assays revealed complete lack of complement-mediated hemolytic activity in the patient's serum. While levels of the complement regulatory proteins Factor I, Factor H and Factor B were normal in the patient's and family members' sera, complement C3 levels were undetectable in the patient's serum and were reduced by at least 50% in the sera of the patient's parents and brother. Additionally, no C3 could be observed in the patient's plasma and cell culture supernatants by Western blot. We also observed that patient's skin fibroblasts stimulated with Escherichia coli LPS were unable to secrete C3, which might be accumulated within the cells before being intracellularly degraded. Sequencing analysis of the patient's C3 cDNA revealed a genetic mutation responsible for the complete skipping of exon 27, resulting in the loss of 99 nucleotides (3450-3549) located in the TED domain. Sequencing of the intronic region between the exons 26 and 27 of the C3 gene (nucleotides 6690313-6690961) showed a nucleotide exchange (T->C) at position 6690626 located in a splicing donor site, resulting in the complete skipping of exon 27 in the C3 mRNA. PMID- 26847112 TI - Long-Term Outcome of Incomplete Revascularization After Percutaneous Coronary Intervention in SCAAR (Swedish Coronary Angiography and Angioplasty Registry). AB - OBJECTIVES: The aim of this study was to describe current practice regarding completeness of revascularization in patients with multivessel disease undergoing percutaneous coronary intervention (PCI) and to investigate the association of incomplete revascularization (IR) with death, repeat revascularization, and myocardial infarction (MI) in a large nationwide registry. BACKGROUND: The benefits of multivessel PCI are controversial. METHODS: Between 2006 and 2010 we identified 23,342 patients with multivessel disease in the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) and merged data with official Swedish health data registries. IR was defined as any nontreated significant (60%) stenosis in a coronary artery supplying >10% of the myocardium. RESULTS: Patients with IR (n = 15,165) were older, had more extensive coronary disease, and more often had ST-segment elevation MI at presentation than those with complete revascularization (CR) (n = 8,177). All-cause 1-year mortality, MI, and repeat revascularization were higher in IR than CR: 7.1% versus 3.8%, 10.4% versus 6.0%, and 20.5% versus 8.5%, respectively. Propensity score methodology was used in the adjusted analyses. Adjusted hazard ratio (HR) for the composite of death, MI, or repeat revascularization at 1 year was higher in IR than CR: 2.12 (95% confidence interval [CI]: 1.98 to 2.28; p < 0.0001). Adjusted HR for death and the combination of death/MI were 1.29 (95% CI: 1.12 to 1.49; p = 0.0005) and 1.42 (95% CI: 1.30 to 1.56; p < 0.0001), respectively. CONCLUSIONS: Incomplete revascularization at the time of hospital discharge in patients with multivessel disease undergoing PCI is associated with a high risk of recurrent 1 year adverse cardiac events. PMID- 26847113 TI - Incomplete Revascularization in Patients Treated With Percutaneous Coronary Intervention: When Enough Is Enough. PMID- 26847115 TI - Accelerate and Decelerate in Primary Percutaneous Coronary Intervention. PMID- 26847114 TI - Randomized Control of Sympathetic Drive With Continuous Intravenous Esmolol in Patients With Acute ST-Segment Elevation Myocardial Infarction: The BEtA-Blocker Therapy in Acute Myocardial Infarction (BEAT-AMI) Trial. AB - OBJECTIVES: This study sought to evaluate the role of esmolol-induced tight sympathetic control in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Elevated sympathetic drive has a detrimental effect on patients with acute STEMI. The effect of beta-blocker-induced heart rate mediated sympathetic control on myocardial damage is unknown. METHODS: The authors conducted a prospective, randomized, single-blind trial involving patients with STEMI and successful percutaneous intervention (Killip class I and II). Patients were randomly allocated to heart rate control with intravenous esmolol for 24 h or placebo. The primary outcome was the maximum change in troponin T release as a prognostic surrogate marker for myocardial damage. A total of 101 patients were enrolled in the study. RESULTS: There was a significant difference between patients allocated to placebo and those who received sympathetic control with esmolol in terms of maximum change in troponin T release: the median serum troponin T concentration increased from 0.2 ng/ml (interquartile range [IQR] 0.1 to 0.7 ng/ml) to 1.3 ng/ml (IQR: 0.6 to 4.7 ng/ml) in the esmolol group and from 0.3 ng/ml (IQR: 0.1 to 1.2 ng/ml) to 3.2 ng/ml (IQR: 1.5 to 5.3 ng/ml) in the placebo group (p = 0.010). The levels of peak creatine kinase (CK), CK subunit MB (CK-MB), and n-terminal brain natriuretic peptide (NT-proBNP) were lower in the esmolol group compared with placebo (CK 619 U/l [IQR: 250-1,701 U/l] vs. 1,308 U/l [IQR: 610 to 2,324 U/l]; p = 0.013; CKMB: 73.5 U/l [IQR: 30 to 192 U/l] vs. 158.5 U/l [IQR: 74 to 281 U/l]; p = 0.005; NT-proBNP: 1,048 pg/ml (IQR: 623 to 2,062 pg/ml] vs. 1,497 pg/ml [IQR: 739 to 3,318 pg/ml]; p = 0.059). Cardiogenic shock occurred in three patients in the placebo group and in none in the esmolol group. CONCLUSIONS: Esmolol treatment statistically significantly decreased troponin T, CK, CK-MB and NT-proBNP release as surrogate markers for myocardial injury in patients with STEMI. (Heart Rate Control After Acute Myocardial Infarction; DRKS00000766). PMID- 26847117 TI - Transcatheter Aortic Valve Replacement and New Conduction Abnormalities/Permanent Pacemaker: Can We Achieve the Intended Implant Depth? PMID- 26847116 TI - Predictors of Permanent Pacemaker Implantations and New-Onset Conduction Abnormalities With the SAPIEN 3 Balloon-Expandable Transcatheter Heart Valve. AB - OBJECTIVES: This study investigates the influence of implantation depth and prosthesis oversizing on conduction abnormalities (CA) and permanent pacemaker implantation (PPI) after SAPIEN 3 (Edwards Lifesciences, Irvine, California) implantation. BACKGROUND: CA and PPIs are frequent complications after transcatheter aortic valve replacement with a next-generation balloon-expandable transcatheter heart valve (SAPIEN 3). The potential underlying mechanisms are incompletely understood. METHODS: Of 244 patients treated with SAPIEN 3,208 without a previous pacemaker and 184 without baseline CA were analyzed. We assessed the association of angiographic implantation depth (% of frame height below the annulus) and degree of oversizing with PPI and CA. RESULTS: New PPI and new or worsened CA or PPI occurred in 16% (34 of 208) and 31% (57 of 184), respectively. Patients requiring PPI had a higher prevalence of atrial fibrillation (44% vs. 24%; p = 0.017), complete right bundle branch block (27% vs. 5%; p = 0.001), and bradycardia (<60 beats/min, 38% vs. 21%; p = 0.034). In patients with new CA or PPI, implantation depth was lower (at septal side: 29 +/- 8% vs. 25 +/- 7%; p = 0.003), and rate of oversizing was higher (19% [11 of 57] vs. 6% [8 of 126]; p = 0.007). Independent predictors of new or worsened CA or PPI were implantation depth at septal side (odds ratio [OR]: 1.063 [95% confidence interval (CI): 1.017 to 1.110]; p = 0.006 per % of frame below the aortic annulus), oversizing (OR: 3.489 [95% CI: 1.236 to 9.848]; p = 0.018), and QRS duration (OR: 1.033 [95% CI: 1.011 to 1.056]; p = 0.003 per ms). CONCLUSIONS: Implantation depth and prosthesis oversizing were associated with a higher rate of new CA or PPI using the SAPIEN 3. Thus, avoidance of deep implantation and extreme oversizing may reduce these complications. PMID- 26847118 TI - Zilver PTX Post-Market Surveillance Study of Paclitaxel-Eluting Stents for Treating Femoropopliteal Artery Disease in Japan: 12-Month Results. AB - OBJECTIVES: This multicenter, prospective, post-market surveillance study in Japan evaluates the paclitaxel-coated Zilver PTX stent in real-world patients with complex lesions. BACKGROUND: The Zilver PTX stent is the first drug-eluting stent (DES) approved for the superficial femoral artery. Previously, results from a large randomized study and a complementary, large single-arm study supported the safety and effectiveness of the DES. METHODS: There were no exclusion criteria, and consecutive patients with symptomatic peripheral artery disease (PAD) treated with the DES were enrolled in the study. Clinically driven target lesion revascularization (TLR) was defined as reintervention performed for >=50% diameter stenosis after recurrent clinical symptoms of PAD. Clinical benefit was defined as freedom from persistent or worsening symptoms of ischemia. Patency was evaluated by duplex ultrasound where physicians considered this standard of care. RESULTS: In this study, 907 patients were enrolled at 95 institutions in Japan. There were numerous comorbidities including high incidences of diabetes (58.8%), chronic kidney disease (43.8%), and critical limb ischemia (21.5%). Lesions were also complex, with an average length of 14.7 cm, 41.6% total occlusions, and 18.6% in-stent restenosis. In total, 1,861 DES were placed in 1,075 lesions. Twelve-month follow-up was obtained for >95% of eligible patients. Freedom from TLR was 91.0%, and clinical benefit was 87.7% through 12 months. The 12-month primary patency rate was 86.4%. CONCLUSIONS: Despite more challenging lesions, results from the current study are similar to outcomes from the previous Zilver PTX studies, confirming the benefit of the Zilver PTX DES in a real-world patient population. (Zilver PTX Post-Market Study in Japan; NCT02254837). PMID- 26847119 TI - Drug-Eluting Stents in the Superficial Femoral Artery: Real-World Versus Randomized Clinical Trials; You Choose, But Caveat Emptor! PMID- 26847121 TI - Unraveling the Biological Effects of Drug-Eluting Stents. PMID- 26847120 TI - Beneficial Effects of a Novel Bioabsorbable Polymer Coating on Enhanced Coronary Vasoconstricting Responses After Drug-Eluting Stent Implantation in Pigs in Vivo. AB - OBJECTIVES: The aim of this study was to examine which component of drug-eluting stents (DES) plays a major role in enhanced coronary vasoconstricting responses after DES implantation in pigs. BACKGROUND: Recent studies have reported unremitting angina due to vasomotion abnormalities even after successful DES implantation. However, it remains to be elucidated which component of DES (metal stent, polymer coating, or antiproliferative drug) is responsible for DES-induced coronary hyperconstricting responses. METHODS: We developed poly-dl-lactic acid and polycaprolactone (PDLLA-PCL) copolymer technology with higher biocompatibility that is resorbed within 3 months. Four types of coronary stents were made: 1) a stent with polylactic acid (PLA) polymer coating containing antiproliferative drug (P1+D+); 2) a stent with PLA polymer coating alone without any drug (P1+D-); 3) a stent with novel PDLLA-PCL polymer coating alone (P2+D-); and 4) a bare metal stent (P-D-). The 4 stents were randomly deployed in the left anterior descending and left circumflex coronary arteries in 12 pigs. RESULTS: After 1 month, coronary vasoconstriction by intracoronary serotonin was enhanced at P1+D+ and P1+D- stent edges compared with P2+D- and P-D- stent edges and was prevented by a specific Rho-kinase (a central molecule of coronary spasm) inhibitor, hydroxyfasudil. Immunostainings showed that inflammatory changes and Rho-kinase activation were significantly enhanced at P1+D+ and P1+D- sites compared with P2+D- and P-D- sites. There were significant positive correlations between the extent of inflammation or Rho-kinase expression/activation and that of coronary vasoconstriction. CONCLUSIONS: These results indicate the important roles of PLA polymer coating in DES-induced coronary vasoconstricting responses through inflammatory changes and Rho-kinase activation in pigs in vivo, which are ameliorated by PDLLA-PCL copolymers. PMID- 26847122 TI - Cancer in the Left Anterior Descending Artery: A Therapeutic Aspect of Thrombus Aspiration? PMID- 26847123 TI - The Bioresorbable Scaffold: Will Oversizing Affect Outcomes? PMID- 26847124 TI - Reply: Fluoroscopy Operators' Brains and Radiation. PMID- 26847125 TI - Does Direct Transcatheter Aortic Valve Replacement Increase the Risk of Cerebral Embolization? PMID- 26847126 TI - Reply: Does Direct Transcatheter Aortic Valve Replacement Increase the Risk of Cerebral Embolization? PMID- 26847127 TI - Immigrants: How Did Andreas Get Here? Part II. PMID- 26847128 TI - Note of clarification regarding data about the association between the interleukin-1beta -31T>C polymorphism and breast cancer risk. PMID- 26847129 TI - Anti-inflammatory potential of ursolic acid in Mycobacterium tuberculosis sensitized and concanavalin A-stimulated cells. AB - Ursolic acid (3-beta-3-hydroxy-urs-12-ene-28-oic-acid; UA) is a triterpenoid carboxylic acid with various pharmaceutical properties. It is commonly found in apples, basil, berries, rosemary, peppermint, lavender, oregano, thyme, hawthorn and prunes. In the present study, the activities of UA against the Mycobacterium tuberculosis H37Rv-induced release of a panel of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL 6 from RAW 264.7 murine macrophages, A549 alveolar epithelial cells and in concanavalin A (Con A)-stimulated rat splenocytes were investigated. In addition, the present study examined the ability of UA to reduce the expression levels of the inflammatory mediators, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in the stimulated cells. The reduction of nitric oxide (NO) release by UA was also examined in the stimulated cells. UA significantly inhibited the mRNA expression levels of TNF-alpha, IL-1beta and IL-6 in the stimulated cells. The expression levels of COX-2 and iNOS were also suppressed by UA, as was the release of NO at a significant level. The data indicated the potency of UA on different cell types, which may assist in the development of anti-inflammatory drugs. In the case of adjunct host-directed immune therapy for tuberculosis, UA may be used, in addition to established antibiotic therapies, to improve treatment efficacy and outcome due to their anti-inflammatory potential. Further detailed investigations are required to establish its use as an anti inflammatory. PMID- 26847130 TI - Loop-mediated isothermal amplification (LAMP) assay for the diagnosis of fasciolosis in sheep and its application under field conditions. AB - BACKGROUND: Loop-mediated isothermal amplification (LAMP) is a very specific, efficient, and rapid gene amplification procedure in which the reaction can run at a constant temperature. In the current study we have developed a LAMP assay to improve the diagnosis of Fasciola spp. in the faeces of sheep. FINDINGS: After the optimisation of the LAMP assay we have shown similar results between this technique and the standard PCR using the outer primers of the LAMP reaction. In both cases the limit of detection was 10 pg; also, the diagnosis of fasciolosis was confirmed during the first week post-infection in experimental infected sheep by both techniques. In eight naturally infected sheep, the infection with F. hepatica was confirmed in all animals before a treatment with triclabendazole and on day 30 post treatment in two sheep using the LAMP assay; however, when we carried out the standard PCR with the outer primers, the results before treatment were the same but on day 30 post-treatment the infection was only confirmed in one out of the two sheep. On the other hand, the standard PCR took around 3 h to obtain a result, comparing with 1 h and 10 min for the LAMP assay. CONCLUSIONS: The LAMP assay described here could be a good alternative to conventional diagnostic methods to detect F. hepatica in faeces since it solves the drawbacks of the standard PCR. PMID- 26847131 TI - Increased expression of FGF1-mediated signaling molecules in adipose tissue of obese mice. AB - Fibroblast growth factors (FGFs) are pleiotropic growth factors that control cell proliferation, migration, and differentiation. Herein, we evaluated whether visceral adiposity of mice is accompanied by the alteration of signaling molecules mediated by fibroblast growth factor receptor 1 (FGFR1) induced by using two different male C57BL/6J mice models of obesity namely high-fat diet (HFD)-induced obesity for 12 weeks or mice with genetic deletion of leptin (ob/ob). Both HFD-fed and ob/ob mice exhibited significantly higher messenger RNA (mRNA) levels of FGF1, cyclin D (cycD), transcription factor E2F1, peroxisome proliferator-activated receptor-gamma 2 (PPAR-gamma2), CCAAT-enhancer-binding protein alpha (C/EBPalpha), and adipocyte protein 2 (aP2) genes in their epididymal adipose tissues compared to those of the normal diet (ND)-fed and lean control mice, respectively. In addition, immunoblot analyses of the epididymal adipose tissues revealed that both mice exposed to HFD and ob/ob mice exhibited elevated phosphorylation of FGFR1, extracellular-signal-regulated kinase (ERK), and retinoblastoma (Rb) proteins. These data support the notion that FGF1 mediated signaling represents an important signaling cascade related to adipogenesis, at least partially, among other known signaling pathways. These new findings regarding the molecular mechanisms controlling adipose tissue plasticity provide a novel insight about the functional network with potential therapeutic application against obesity. PMID- 26847132 TI - Donor TSH level is associated with clinical pregnancy among oocyte donation cycles. AB - PURPOSE: The purpose of the study is to evaluate the association between donor TSH level (independent of recipient TSH level) and recipient pregnancy outcome among fresh donor oocyte IVF cycles. METHODS: This is a retrospective cohort study investigating 232 consecutive fresh donor-recipient cycles (200 total oocyte donors) at an academic medical center. Main outcome measures include clinical pregnancy and live birth. RESULTS: Cycles were categorized into two groups based on donor TSH level (< 2.5 and >= 2.5 mIU/L). After controlling for multiple donor and recipient characteristics, the probability of clinical pregnancy was significantly lower among donors with TSH levels >=2.5 mIU/L compared to those with TSH values <2.5 mIU/L (43.1 %, 95 % CI 28.5-58.9, versus 66.7 %, 95 % CI 58.6-73.9, respectively, p = 0.01). The difference in live birth rates between the two groups did not achieve statistical significance (43.1 %, 95 % CI 28.8-58.6, versus 58.0 %, 95 % CI 50.0-65.6, respectively, p = 0.09). CONCLUSIONS: Donor TSH level, independent of recipient TSH level, is associated with recipient clinical pregnancy. These findings suggest that thyroid function may impact the likelihood of pregnancy at the level of the oocyte. PMID- 26847133 TI - Validation-verification of a highly effective, practical human testicular tissue in vitro culture-cryopreservation procedure aimed to optimize pre-freeze and post thaw motility. AB - PURPOSE: The aim of our paper was to validate a testicular biopsy procedure that simplifies handling, processing, and cryopreservation, while at the same time optimizes sperm motility before freezing and after thawing. METHODS: Two prospective studies were conducted to verify, optimize, and understand the virtues of pre-freeze testicular tissue IVC at different temperatures (21, 30, or 37 degrees C). Testicular tissue was obtained from clinical specimens designated for whole tissue cryopreservation (i.e., intact mass of tubules) and/or for fresh use in IVF-ICSI cycles. Whole testicular biopsy pieces (1-3 mm(3)) were diluted in glycerol containing freeze solutions, slow cooled to 4 degrees C and then rapidly frozen in LN2 vapor. Fresh and post-thaw testicular biopsy tissue were evaluated for changes in the quantity (%) and pattern of motility (I-IV: twitching to rapid progression, respectively) over a 1 week duration. The clinical effectiveness of IVC-cryopreserved whole testicular biopsy tissue was also validated analyzing fresh embryo transfers. RESULTS: More reliable recovery of motile testicular sperm was achieved using whole tissue freeze preservation combined with IVC (24-96 h) post-acquisition at an incubation temperature of 30 degrees C compared to ambient temperature (21 degrees C) or 37 degrees C. Up to 85 % of the pre-freeze motility was conserved post-thaw (+3 h) for easy ICSI selection. Sperm longevity was optimized to fresh tissue levels by implementing testicular biopsy sucrose dilution post-thaw. Favorable clinical outcomes were proven using frozen-thawed testicular biopsy sperm for ICSI. CONCLUSIONS: By employing minimal tissue manipulation, integrating pre-freeze IVC processing at 30 degrees C and the freezing of whole testicular biopsy tissue, we have reduced the labor and improved the efficacy of processing testicular tissue for freeze preservation and subsequent ICSI use. PMID- 26847134 TI - School Nurses on the Front Lines of Medicine: Emergencies 101 Ask the E.R. Pediatrician. AB - Pediatric emergencies, such as the exacerbation of medical conditions and injuries, may occur in the school setting. This article introduces the "School Nurses on the Front Lines of Medicine" series by discussing the incidence and the most common emergencies that occur in schools as well as published guidelines for school emergency preparedness. PMID- 26847135 TI - Reaction time and onset of psychological distress: the UK Health and Lifestyle Survey. AB - BACKGROUND: Cross-sectional studies have shown that depression is often accompanied by less efficient cognitive function, as indicated by slower speed of information processing. The direction of effect is unclear. We investigated prospectively whether slower processing speed, as indexed by longer simple or choice reaction time, is associated with an increased risk of psychological distress. METHODS: Participants were 3088 men and women aged 18 and over who had taken part in the UK Health and Lifestyle Survey. Simple and choice reaction time was measured in the baseline survey. Symptoms of psychological distress were assessed at baseline and at the 7-year follow-up survey with the 30-item General Health Questionnaire (GHQ). RESULTS: In unadjusted models, a SD slower simple or choice reaction time at baseline was associated with ORs for psychological distress (>=5 on GHQ) at follow-up of 1.14 (1.06 to 1.23; p<0.001) or 1.13 (1.04 to 1.22; p=0.002), respectively. Further adjustment for age, sex, social class, educational attainment, health behaviours, number of chronic physical illnesses present, neuroticism and GHQ score at baseline had only slight attenuating effects on these associations. In fully adjusted models, a SD slower simple or choice reaction time at baseline was associated with ORs for psychological distress of 1.11 (1.02 to 1.21; p=0.017) or 1.11 (1.00 to 1.24; p=0.048), respectively. CONCLUSIONS: Slower processing speed may be a risk factor for the development of psychological distress. Future studies should explore the extent to which slower processing speed explains previously demonstrated associations between lower intelligence and poorer mental health. PMID- 26847136 TI - Health systems: how much difference can they make to health inequities? PMID- 26847138 TI - Organocatalytic Kinetic Resolution of Sulfoximines. AB - An efficient kinetic resolution of sulfoximines with enals was realized using chiral N-heterocyclic carbene (NHC) catalysts. The stereoselective amidation proceeds without additional acyl transfer agent. Both enantiomers of the sulfoximines can be obtained with excellent ee values (up to 99% ee and -97% ee, respectively). Performing the catalysis on a gram scale allowed using the recovered sulfoximine (+)-1j in an asymmetric synthesis of FXa inhibitor F. PMID- 26847137 TI - I owe you: age-related similarities and differences in associative memory for gains and losses. AB - Older adults often experience associative memory impairments but can sometimes remember important information. The current experiments investigate potential age related similarities and differences associate memory for gains and losses. Younger and older participants were presented with faces and associated dollar amounts, which indicated how much money the person "owed" the participant, and were later given a cued recall test for the dollar amount. Experiment 1 examined face-dollar amount pairs while Experiment 2 included negative dollar amounts to examine both gains and losses. While younger adults recalled more information relative to older adults, both groups were more accurate in recalling the correct value associated with high-value faces compared to lower-value faces and remembered gist-information about the values. However, negative values (losses) did not have a strong impact on recall among older adults versus younger adults, illustrating important associative memory differences between younger and older adults. PMID- 26847139 TI - Urodynamic Testing for Men with Voiding Symptoms Considering Interventional Therapy: The Merits of a Properly Constructed Randomised Trial. AB - Insufficient evidence exists regarding the role of invasive urodynamics in routine practice in the clinical assessment of male lower urinary tract symptoms. UPSTREAM, a multicentre randomised trial, will inform patients, clinicians, and policy-makers about whether urodynamics should be more widely used for such patients. PMID- 26847140 TI - How might health services capture patient-reported safety concerns in a hospital setting? An exploratory pilot study of three mechanisms. AB - INTRODUCTION: Emergent evidence suggests that patients can identify and report safety issues while in hospital. However, little is known about the best method for collecting information from patients about safety concerns. This study presents an exploratory pilot of three mechanisms for collecting data on safety concerns from patients during their hospital stay. METHOD: Three mechanisms for capturing safety concerns were coproduced with healthcare professionals and patients, before being tested in an exploratory trial using cluster randomisation at the ward level. Nine wards participated, with each mechanism being tested over a 3-month study period. Patients were asked to feed back safety concerns via the mechanism on their ward (interviewing at their bedside, paper-based form or patient safety 'hotline'). Safety concerns were subjected to a two-stage review process to identify those that would meet the definition of a patient safety incident. Differences between mechanisms on a range of outcomes were analysed using inferential statistics. Safety concerns were thematically analysed to develop reporting categories. RESULTS: 178 patients were recruited. Patients in the face-to-face interviewing condition provided significantly more safety concerns per patient (1.91) compared with the paper-based form (0.92) and the patient safety hotline (0.43). They were also significantly more likely to report one or more concerns, with 64% reporting via the face-to-face mechanism, compared with 41% via the paper-based form and 19% via the patient safety hotline. No mechanism differed significantly in the number of classified patient safety incidents or physician-rated preventability and severity. DISCUSSION: Interviewing at the patient's bedside is likely to be the most effective means of gathering safety concerns from inpatients, potentially providing an opportunity for health services to gather patient feedback about safety from their perspective. PMID- 26847141 TI - Complications Following Inpatient Extracapsular Tonsillectomy in Children 36 Months and Younger. AB - IMPORTANCE: Tonsillectomy is among the most common surgical procedures performed by general and pediatric otolaryngologists. Inpatient surgery is generally recommended for children 36 months and younger owing to concern for a higher incidence of postoperative complications. OBJECTIVE: To ascertain the need for a planned inpatient stay for extracapsular tonsillectomy in children 36 months and younger. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review of patients 36 months and younger who underwent inpatient extracapsular tonsillectomy or adenotonsillectomy at a tertiary care academic institution from January 2009 to September 2014. Of 279 medical records reviewed, 188 met the inclusion criteria for the study. INTERVENTIONS: Extracapsular tonsillectomy. MAIN OUTCOMES AND MEASURES: Inpatient notes, discharge summaries, and postoperative clinic visit notes in the electronic medical record were reviewed for information about complications occurring during postoperative inpatient hospitalization. Specifically, the incidence of postoperative hemorrhage, postoperative pulmonary edema, oxygen desaturation to less than 90% requiring supplemental oxygen overnight, overall poor oral intake, poor oral intake leading to prolonged hospitalization exceeding 1 day, return to the operating room, and mortality were determined. RESULTS: The 188 patients in the study ranged in age from 18.3 to 35.9 months (mean, 29.5 months). Among the patients, 183 (97.3%) underwent surgery for sleep-disordered breathing, 2 (1.1%) were reintubated for postobstructive pulmonary edema, 1 (0.5%) experienced a self-limited postoperative hemorrhage, 5 (2.7%) required supplemental oxygen postoperatively, and 30 (15.9%) had poor oral intake postoperatively on the day of surgery. The hospital stay for 9 patients (4.8%) exceeded 1 day because of poor oral intake. No patients had to return to the operating room during their hospitalization and there were no deaths of patients in the population studied. CONCLUSIONS AND RELEVANCE: Very few children experienced postoperative complications during their hospitalization, suggesting that outpatient tonsillectomy and adenotonsillectomy may be safe in children in this age group. Overnight hospitalization of children in this age group may not always be necessary after an appropriate period of postoperative observation. PMID- 26847143 TI - Endemicity of chytridiomycosis features pathogen overdispersion. AB - Pathogens can be critical drivers of the abundance and distribution of wild animal populations. The presence of an overdispersed pathogen load distribution between hosts (where few hosts harbour heavy parasite burdens and light infections are common) can have an important stabilizing effect on host-pathogen dynamics where infection intensity determines pathogenicity. This may potentially lead to endemicity of an introduced pathogen rather than extirpation of the host and/or pathogen. Overdispersed pathogen load distributions have rarely been considered in wild animal populations as an important component of the infection dynamics of microparasites such as bacteria, viruses, protozoa and fungi. Here we examined the abundance, distribution and transmission of the model fungal pathogen Batrachochytrium dendrobatidis (Bd, cause of amphibian chytridiomycosis) between wild-caught Litoria rheocola (common mist frogs) to investigate the effects of an overdispersed pathogen load distribution on the host population in the wild. We quantified host survival, infection incidence and recovery probabilities relative to infectious burden, and compared the results of models where pathogen overdispersion either was or was not considered an important feature of host-pathogen dynamics. We found the distribution of Bd load between hosts to be highly overdispersed. We found that host survival was related to infection burden and that accounting for pathogen overdispersion allowed us to better understand infection dynamics and their implications for disease control. In addition, we found that the pattern of host infections and recoveries varied markedly with season whereby (i) infections established more in winter, consistent with temperature-dependent effects on fungal growth, and (ii) recoveries (loss of infection) occurred frequently in the field throughout the year but were less likely in winter. Our results suggest that pathogen overdispersion is an important feature of endemic chytridiomycosis and that intensity of infection determines disease impact. These findings have important implications for our understanding of chytridiomycosis dynamics and the application of management strategies for disease mitigation. We recommend quantifying individual infectious burdens rather than infection state where possible in microparasitic diseases. PMID- 26847142 TI - The fully synthetic MAG-Tn3 therapeutic vaccine containing the tetanus toxoid derived TT830-844 universal epitope provides anti-tumor immunity. AB - Malignant transformations are often associated with aberrant glycosylation processes that lead to the expression of new carbohydrate antigens at the surface of tumor cells. Of these carbohydrate antigens, the Tn antigen is particularly highly expressed in many carcinomas, especially in breast carcinoma. We designed MAG-Tn3, a fully synthetic vaccine based on three consecutive Tn moieties that are O-linked to a CD4+ T cell epitope, to induce anti-Tn antibody responses that could be helpful for therapeutic vaccination against cancer. To ensure broad coverage within the human population, the tetanus toxoid-derived peptide TT830 844 was selected as a T-helper epitope because it can bind to various HLA-DRB molecules. We showed that the MAG-Tn3 vaccine, which was formulated with the GSK proprietary immunostimulant AS15 and designed for human cancer therapy, is able to induce an anti-Tn antibody response in mice of various H-2 haplotypes, and this response correlates with the ability to induce a specific T cell response against the TT830-844 peptide. The universality of the TT830-844 peptide was extended to new H-2 and HLA-DRB molecules that were capable of binding this T cell epitope. Finally, the MAG-Tn3 vaccine was able to induce anti-Tn antibody responses in cynomolgus monkeys, which targeted Tn-expressing tumor cells and mediated tumor cell death both in vitro and in vivo. Thus, MAG-Tn3 is a highly promising anticancer vaccine that is currently under evaluation in a phase I clinical trial. PMID- 26847144 TI - Evidence for Rhythmicity Pacemaker in the Calcification Process of Scleractinian Coral. AB - Reef-building scleractinian (stony) corals are among the most efficient bio mineralizing organisms in nature. The calcification rate of scleractinian corals oscillates under ambient light conditions, with a cyclic, diurnal pattern. A fundamental question is whether this cyclic pattern is controlled by exogenous signals or by an endogenous 'biological-clock' mechanism, or both. To address this problem, we have studied calcification patterns of the Red Sea scleractinian coral Acropora eurystoma with frequent measurements of total alkalinity (AT) under different light conditions. Additionally, skeletal extension and ultra structure of newly deposited calcium carbonate were elucidated with (86)Sr isotope labeling analysis, combined with NanoSIMS ion microprobe and scanning electron microscope imaging. Our results show that the calcification process persists with its cyclic pattern under constant light conditions while dissolution takes place within one day of constant dark conditions, indicating that an intrinsic, light-entrained mechanism may be involved in controlling the calcification process in photosymbiotic corals. PMID- 26847145 TI - Licochalcone B induces apoptosis of human oral squamous cell carcinoma through the extrinsic- and intrinsic-signaling pathways. AB - Licochalcone B (Lico B), which belongs to the retrochalcone family, is isolated from the roots of Chinese licorice. Lico B has been reported to have several other useful pharmacological properties, such as anti-inflammatory, antibacterial, antioxidant, antiulcer, anticancer, and anti-metastasis activities. We elucidated the underlying mechanism by which Lico B can induce apoptosis in oral squamous cell carcinoma (OSCC). Our results showed that exposure of OSCC cells (HN22 and HSC4) to Lico B significantly inhibited cell proliferation in a time- and concentration-dependent manner. Lico B caused cell cycle arrest at G1 phase along with downregulation of cyclin D1 and upregulation of p21 and p27 proteins. Lico B also facilitated the diffusion of phospholipid phosphatidylserine (PS) from inner to outer leaflets of the plasma membrane with chromatin condensation, DNA fragmentation, accumulated sub-G1 population in a concentration-dependent manner. Moreover, Lico B promoted the generation of reactive oxygen species (ROS), which, in turn, can induce CHOP, death receptor (DR) 4 and DR5. Lico B treatment induced downregulation of anti-apoptotic proteins (Bid and Bcl-xl and Mcl-1), and up-regulation of pro-apoptotic protein (Bax). Lico B also led to the loss of mitochondrial membrane potential (MMP), resulting in cytochrome c release. As can be expected from the above results, the apoptotic protease activating factor-1 (Apaf-1) and survivin were oppositely expressed in favor of apoptotic cell death. This notion was supported by the fact that Lico B activated multi-caspases with cleavage of poly (ADP-ribose) polymerase (PARP) protein. Therefore, it is suggested that Lico B is a promising drug for the treatment of human oral cancer via the induction of apoptotic cell death. PMID- 26847146 TI - Peripheral nervous system involvement in primary burning mouth syndrome--results of a pilot study. AB - OBJECTIVE: The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, but recent studies suggest pathology within the nervous system at multiple levels. This study aimed to investigate in detail the contribution of either focal or generalized alterations within the peripheral nervous system (PNS) in the etiopathogenesis of BMS. SUBJECTS AND METHODS: Intraepithelial nerve fiber density (IENFD) of tongue mucosa was assessed in 10 carefully characterized BMS, and the results were compared to 19 age- and gender matched cadaver controls, 6 with lifetime diabetes. Extensive neurophysiologic and psychophysical examinations of the trigeminal system and distal extremities were performed to profile PNS function in BMS. RESULTS: Patients with BMS had significantly fewer intraepithelial nerve fibers (0,27, s.e. 0,18 mm(-1); P = 0.0253) than non-diabetic controls (0,92, s.e. 0,15 mm(-1)). In the subepithelial space, the amount of nerve fibers did not differ between the groups. The majority (9/10) of patients with BMS showed neurophysiologic or psychophysical signs of a more generalized PNS dysfunction. CONCLUSIONS: Our results in neurophysiologically optimally characterized BMS patients confirm that pure focal small fiber neuropathy of the oral mucosa has a role in the pathophysiology of primary BMS. Furthermore, BMS may be related to a more generalized, yet subclinical peripheral neuropathy. PMID- 26847147 TI - Extracellular matrix degradation via enolase/plasminogen interaction: Evidence for a mechanism conserved in Metazoa. AB - BACKGROUND INFORMATION: While enolase is a ubiquitous metalloenzyme involved in the glycolytic pathway, it is also known as a multifunctional protein, since enolases anchored on the outer surface of the plasma membrane are involved in tissue invasion. RESULTS: We have identified an extracellular enolase (Ae-ENO) produced by the teratocytes, embryonic cells of the insect parasitoid Aphidius ervi. We demonstrate that Ae-ENO, although lacking a signal peptide, accumulates in cytoplasmic vesicles oriented towards the cell membrane. Ae-ENO binds to and activates a plasminogen-like molecule inducing digestion of the host tissue and thereby ensuring successful parasitism. CONCLUSIONS: These results support the hypothesis that plasminogen-like proteins exist in invertebrates. Interestingly the activation of a plasminogen-like protein is mediated by a mechanisms involving the surface enolase/fibrinolytic system considered, until now, exclusive of vertebrates, and that instead is conserved across species. SIGNIFICANCE: To our knowledge, this is the first example of enolase mediated Plg like binding and activation in insect cells, demonstrating the existence of an ECM degradation process via a Plg-like protein in invertebrates. PMID- 26847148 TI - Modulation of Endothelial Injury Biomarkers by Traditional Chinese Medicine LC in Systemic Lupus Erythematosus Patients Receiving Standard Treatments. AB - LC is an herbal remedy effectively reduced therapeutic dosage of glucocorticoid for systemic lupus erythematosus (SLE) patients in clinical trial (ISRCTN81818883). This translational research examined the impact of LC on biomarkers of endothelial injury in the enrolled subjects. Fifty seven patients with SLE were randomized to receive standard treatment without or with LC supplements. Blood samples were taken serially for quantification of endothelial progenitor cells (EPCs), circulating endothelial cells (CECs) and serological factors. The proportion of EPCs in the placebo group continued to increase during trial and was further elevated after withdrawal of standard treatment. The EPC ratio of LC group remained stationary during the entire observation period. The CEC ratio in placebo group exhibited an increasing trend whereas that in LC group declined. The ratio of apoptotic CECs had an increasing trend in both groups, to a lesser extent in LC group. After treatment, the levels of VEGF and IL-18 have a trend declined to a level lower in the LC group than the placebo group. No significant alteration was noted in serum levels of IFN-alpha, IL-1beta and IL-6. The reduction of the steroid dosage by adding LC might be correlated with less extensive endothelial injury in SLE patients. PMID- 26847149 TI - Positive Reinforcement Training for Blood Collection in Grizzly Bears (Ursus arctos horribilis) Results in Undetectable Elevations in Serum Cortisol Levels: A Preliminary Investigation. AB - Training nonhuman animals in captivity for participation in routine husbandry procedures is believed to produce a lower stress environment compared with undergoing a general anesthetic event for the same procedure. This hypothesis rests largely on anecdotal evidence that the captive subjects appear more relaxed with the trained event. Blood markers of physiological stress responses were evaluated in 4 captive grizzly bears (Ursus arctos horribilis) who were clicker trained for blood collection versus 4 bears who were chemically immobilized for blood collection. Serum cortisol and immunoglobulin A (IgA) and plasma beta endorphin were measured as indicators of responses to stress. Plasma beta endorphin was not different between the groups. Serum IgA was undetectable in all bears. Serum cortisol was undetectable in all trained bears, whereas chemically immobilized bears had marked cortisol elevations (p < .05). The highest cortisol elevations were found in 2 bears with extensive recent immobilization experience. These findings support the use of positive reinforcement training for routine health procedures to minimize anxiety. PMID- 26847150 TI - Erratum: SIMcheck: a Toolbox for Successful Super-resolution Structured Illumination Microscopy. PMID- 26847151 TI - Patient empanelment: A strategy to improve continuity and quality of patient care. AB - PROBLEM: In some Federally-Qualified Community Health Centers (FQHCs), patients do not have a designated primary care provider (PCP). Patients see any provider who is available. This leads to fragmented care, poorer outcomes, and higher costs. DESIGN: Patients were empaneled to a designated PCP. Continuity, quality, and efficiency measures were collected at baseline, 6-, and 12-months postempanelment. BACKGROUND AND SETTING: Three rural FQHCs on the coast of Northern California performing about 18,000 patient visits annually. KEY MEASURES FOR IMPROVEMENT: Patient cycle time, percentage of patient visits with designated PCPs, completion of cervical and colorectal cancer screenings; blood pressure, low-density lipoprotein, and hemoglobin A1c control in patients with diabetes. STRATEGIES FOR CHANGE: The senior Leadership Team initiated the patient empanelment project with the assistance of an outside consultant. EFFECTS OF CHANGE: After 12 months, 100% of the FQHC's patients were assigned a PCP and saw that provider on >=63% of visits. Quality indicators improved by an average of 9% and cycle time decreased by 12 min. per patient allowing providers to see approximately four more patients and generate an additional $2212 per day. LESSONS LEARNT: Project outcomes supported the importance of a designated PCP to achieve improved quality and efficiency of care. PMID- 26847152 TI - Effect of a Single Session of a Yogic Meditation Technique on Cognitive Performance in Medical Students: A Randomized Crossover Trial. AB - Medical students confront enormous academic, psychosocial, and existential stress throughout their training, leading to a cascade of consequences both physically and psychologically. The declined cognitive function of these students interferes in their academic performance and excellence. The purpose of this study was to examine the effectiveness of a yogic meditation technique, mind sound resonance technique (MSRT), on cognitive functions of University Medical students in a randomized, two-way crossover study. In total, 42 healthy volunteers of both genders (5 males and 37 females) with mean age of 19.44 +/- 1.31 years were recruited from a medical college in South India, based on the inclusion and exclusion criteria. A 10-day orientation in the technique of MSRT was given to all the recruited subjects after which each subject underwent both MSRT and supine rest (SR) sessions. All participants were randomized in a 1:1 ratio to receive a session of either MSRT or SR. After a day of washout, participants crossed over to receive the alternative intervention. The cognitive functions were assessed using 2 paper-pencil tasks called Digit Letter Substitution Test (DLST) and Six-Letter Cancelation Task (SLCT), before and immediately after both sessions. Both the groups showed significant improvement in net attempt of both DLST and SLCT, but the magnitude of change was more in the MSRT group than in the SR group. The MSRT group demonstrated significantly enhanced net scores in both SLCT (p < 0.001) and DLST (p < 0.001). The result of the present study suggests that a single session of MSRT, a Mind-Body Practice, may positively impact the performance in cognitive tasks by the University Medical Students. PMID- 26847153 TI - Latent trajectories of adolescent antisocial behavior: Serotonin transporter linked polymorphic region (5-HTTLPR) genotype influences sensitivity to perceived parental support. AB - Although prevailing theories of antisocial behavior (ASB) emphasize distinct developmental trajectories, few studies have explored gene-environment interplay underlying membership in empirically derived trajectories. To improve knowledge about the development of overt (e.g., aggression) and covert (e.g., delinquency) ASB, we tested the association of the 44-base pair promoter polymorphism in the serotonin transporter linked polymorphic region gene (5-HTTLPR), perceived parental support (e.g., closeness and warmth), and their interaction with ASB trajectories derived using latent class growth analysis in 2,558 adolescents followed prospectively into adulthood from the National Longitudinal Study of Adolescent Health. Three distinct trajectories emerged for overt (low desisting, adolescent peak, and late onset) and covert ASB (high stable, low stable, and nonoffending). Controlling for sex, parental support inversely predicted membership in the adolescent-peak overt ASB trajectory (vs. low desisting), but was unrelated to class membership for covert ASB. Furthermore, the 5-HTTLPR genotype significantly moderated the association of parental support on overt ASB trajectory membership. It is interesting that the pattern of Gene * Environment interaction differed by trajectory class: whereas short allele carriers were more sensitive to parental support in predicting the late-onset trajectory, the long/long genotype functioned as a potential "plasticity genotype" for the adolescent-peak trajectory group. We discuss these preliminary findings in the context of the differential susceptibility hypothesis and discuss the need for future studies to integrate gene-environment interplay and prospective longitudinal designs. PMID- 26847154 TI - Cationic 1,2,3-Triazolium Alkynes: Components To Enhance 1,4-Regioselective Azide Alkyne Cycloaddition Reactions. AB - 4-Alkynyl-1,2,3-triazolium cations undergo thermal [3 + 2] cycloaddition reactions with azides roughly 50- to 100-fold faster than comparable noncharged alkynes. Further, the reaction is highly 1,4-regioselective (dr up to 99:1) owing to the selective stabilization of 1,4-TS transition states via conjugative pi acceptor assistance of the alkyne triazolium ring. The novel cationic triazolium alkynes also accelerate the CuAAC reaction to provide bis(1,2,3-triazoles) in an "ultrafast" way (<5 min). PMID- 26847155 TI - Tunable ultrasensitivity: functional decoupling and biological insights. AB - Sensitivity has become a basic concept in biology, but much less is known about its tuning, probably because allosteric cooperativity, the best known mechanism of sensitivity, is determined by rigid conformations of interacting molecules and is thus difficult to tune. Reversible covalent modification (RCM), owing to its systems-level ingenuity, can generate concentration based, tunable sensitivity. Using a mathematical model of regulated RCM, we find sensitivity tuning can be decomposed into two orthogonal modes, which provide great insights into vital biological processes such as tissue development and cell cycle progression. We find that decoupling of the two modes of sensitivity tuning is critical to fidelity of cell fate decision; the decoupling is thus important in development. The decomposition also allows us to solve the 'wasteful degradation conundrum' in budding yeast cell cycle checkpoint, which further leads to discovery of a subtle but essential difference between positive feedback and double negative feedback. The latter guarantees revocability of stress-induced cell cycle arrest; while the former does not. By studying concentration conditions in the system, we extend applicability of ultrasensitivity and explain the ubiquity of reversible covalent modification. PMID- 26847156 TI - Big atria, little P waves: unexpected mismatch between chamber volume and electrocardiogram signal in "false" atrial fibrillation. PMID- 26847157 TI - Physical examination along with point-of-care echocardiography: an indisputable right path. PMID- 26847158 TI - Long-term 3-Dimensional Volume Assessment After Fat Repositioning Lower Blepharoplasty. AB - IMPORTANCE: First reported 3-dimensional quantitative study of the lower periorbital area after lower blepharoplasty using the fat repositioning technique. OBJECTIVE: To determine the volumetric effects lower blepharoplasty with fat repositioning provides to the tear trough and deep fat compartments of the upper cheek. DESIGN, SETTING, AND PARTICIPANTS: A retrospective electronic medical chart review (16-month study with a minimum of 10-month postoperative evaluation) was performed on 12 initial patients recruited to a private practice; 2 patients were lost to long-term follow-up. Patients were recruited between May 2014 and November 2014. To fulfill recruitment criteria, patients must have undergone a lower blepharoplasty performed using the fat repositioning technique with a minimum of 10 months follow-up. Patients who had undergone additional procedures or had a history of filler to the tear trough or cheek area before or during the study period were excluded. MAIN OUTCOMES AND MEASURES: Volume (mL) measurement of a defined anatomical area in postoperative patients. RESULTS: Overall, 10 patients (mean [range] age, 56 [37-66] years) who had undergone a lower blepharoplasty performed using the fat repositioning technique had volume gain in the areas evaluated. The mean (range) follow-up time was 12 (10-16) months. The average volume gain was 0.64 mL (left side, 0.61 mL; right side, 0.67 mL). There was no statistical difference when the 2 sides were compared (P = .49). CONCLUSIONS AND RELEVANCE: The fat repositioning technique in lower blepharoplasty improves pseudofat herniation while simultaneously adding volume to the lower periorbital and cheek areas. The results are reproducible with long term aesthetic improvement in the tear trough and upper cheek areas. LEVEL OF EVIDENCE: 4. PMID- 26847159 TI - Analytical and clinical comparison of different immunoassay systems for the detection of antiphospholipid antibodies. AB - INTRODUCTION: We evaluated analytical and clinical performances of IgG and IgM anticardiolipin (aCL) antibodies and anti-beta2-glycoprotein I (a-beta2GpI) antibodies and upper limit reference ranges (99th percentiles) in comparison with manufacturer's cutoff values with different commercial methods. METHODS: We assayed aCL and a-beta2GpI in serum samples from 30 healthy individuals, 77 patients with antiphospholipid syndrome (APS) diagnosed according to the Sydney criteria, 51 patients with autoimmune diseases, eight patients with previous thrombotic events, six patients with other diseases, and 18 patients with infectious diseases, using ELISA Inova Diagnostics; EliA Phadia Laboratory Systems; CliA Zenit-RA; and CliA Bio-Flash. RESULTS: Anticardiolipin and a beta2GpI IgG and IgM immunoassays showed good analytic performances with both 99th percentile and manufacturer's cutoff reference values. Our results showed fair to moderate agreement among assays. In-house cutoff values gave significantly better performances only for a-beta2GpI IgG with all the immunoassays analyzed with the exception of Inova CliA Bio-Flash where we obtained the same performances with in-house and manufacturer's cutoffs. CONCLUSIONS: By guidelines, all laboratories are strongly advised to validate/verify the manufacturer's cutoff values. We recommend establishing low positive, medium-/high-positive, and high-positive CliA IgG aCL and a-beta2GpI ranges in order to help clinicians in the diagnosis and treatment of APS. PMID- 26847160 TI - Individual Differences in Rhythmic Cortical Entrainment Correlate with Predictive Behavior in Sensorimotor Synchronization. AB - The current study aims at characterizing the mechanisms that allow humans to entrain the mind and body to incoming rhythmic sensory inputs in real time. We addressed this unresolved issue by examining the relationship between covert neural processes and overt behavior in the context of musical rhythm. We measured temporal prediction abilities, sensorimotor synchronization accuracy and neural entrainment to auditory rhythms as captured using an EEG frequency-tagging approach. Importantly, movement synchronization accuracy with a rhythmic beat could be explained by the amplitude of neural activity selectively locked with the beat period when listening to the rhythmic inputs. Furthermore, stronger endogenous neural entrainment at the beat frequency was associated with superior temporal prediction abilities. Together, these results reveal a direct link between cortical and behavioral measures of rhythmic entrainment, thus providing evidence that frequency-tagged brain activity has functional relevance for beat perception and synchronization. PMID- 26847161 TI - Maternal 'near miss' at Royal Darwin Hospital: An analysis of severe maternal morbidity at an Australian regional tertiary maternity unit. AB - BACKGROUND: Assessment of severe maternal morbidity using World Health Organization (WHO) 'near-miss' criteria is gaining in importance as a valuable tool in the assessment of maternity care of women. Identification of cases allows an understanding of aetiology of severe morbidity and factors contributing to poor maternal outcomes. AIM: The aim of this study is to determine the rate of maternal 'near miss' at Royal Darwin Hospital (RDH) and the utility of the WHO near-miss criteria as a tool for data collection in a regional Australian context. METHODS AND MATERIALS: Cases of maternal 'near miss' and deaths were prospectively identified over a period of 12 months using the WHO criteria. RESULTS: During the audit period, there were 2080 live births at Royal Darwin Hospital (RDH): 10 women presented with a 'near miss' and there was one maternal death. The maternal mortality ratio for the hospital was 48/100 000 live births, the maternal 'near-miss' index ratio was 4.8/1000 live births, and the combination of maternal deaths and near misses gave a severe maternal outcome (SMO) ratio of 5.3/1000 live births. The main cause of obstetric 'near miss' was obstetric haemorrhage. Indigenous women and women from remote areas comprised a significant portion of 'near-miss' cases. CONCLUSION: The rates of maternal 'near miss' at RDH are consistent with other studies in the developed world. The WHO maternal 'near-miss' audit tool helps health professionals understand and anticipate severe maternal morbidities, with the aim of improving maternal and perinatal outcomes. PMID- 26847163 TI - Anisotropic structure and dynamics of the solvation shell of a benzene solute in liquid water from ab initio molecular dynamics simulations. AB - The anisotropic structure and dynamics of the hydration shell of a benzene solute in liquid water have been investigated by means of ab initio molecular dynamics simulations using the BLYP (Becke-Lee-Yang-Parr) and dispersion corrected BLYP-D functionals. The main focus has been to look at the influence of pi-hydrogen bonding and hydrophobic interactions on the distance and angle resolved various structural and dynamic properties of solvation shell. The structure of hydration shell water molecules around benzene is found to be highly anisotropic as revealed by the radial distribution functions of different conical regions and joint radial/angular distribution functions. The benzene-water dimer potential energy curves are calculated for a variety of orientations of water along the axial and equatorial directions for both BLYP and BLYP-D functionals. The simulation results of the hydration shell structure of benzene, particularly the axial and equatorial benzene-water RDFs are discussed based on the differences in the benzene-water potential energies for different orientations and functionals. The inter-particle distance/angle correlations show an enhanced water structure in the solvation shell of benzene compared to that between the solvation shell and bulk and also between the bulk molecules. On average, a single piH-bond is found to be formed between water and benzene in the 45 degrees axial conical region of the solvation shell. The piH-bonded water molecules are found to have faster translational dynamics and also found to follow a fast jump mechanism of reorientation to change their hydrogen bonded partners. The presence of pi hydrogen-bonded water makes the overall dynamics of the axial region faster than that of the equatorial region where the water molecules are hydrophobically solvated and hydrogen bonded to other water molecules. PMID- 26847162 TI - Tuning of the Na,K-ATPase by the beta subunit. AB - The vital gradients of Na(+) and K(+) across the plasma membrane of animal cells are maintained by the Na,K-ATPase, an alphabeta enzyme complex, whose alpha subunit carries out the ion transport and ATP hydrolysis. The specific roles of the beta subunit isoforms are less clear, though beta2 is essential for motor physiology in mammals. Here, we show that compared to beta1 and beta3, beta2 stabilizes the Na(+)-occluded E1P state relative to the outward-open E2P state, and that the effect is mediated by its transmembrane domain. Molecular dynamics simulations further demonstrate that the tilt angle of the beta transmembrane helix correlates with its functional effect, suggesting that the relative orientation of beta modulates ion binding at the alpha subunit. beta2 is primarily expressed in granule neurons and glomeruli in the cerebellum, and we propose that its unique functional characteristics are important to respond appropriately to the cerebellar Na(+) and K(+) gradients. PMID- 26847164 TI - Has the use of talc an effect on yield and extra virgin olive oil quality? AB - The maximization of both extraction yield and extra virgin olive oil quality during olive processing are the main objectives of the olive oil industry. As regards extraction yield, it can be improved by both acting on time/temperature of malaxation and using physical coadjuvants. It is well known that, generally, increasing temperature of malaxation gives an increase in oil extraction yield due to a reduction in oily phase viscosity; however, high malaxation temperature can compromise the nutritional and health values of extra virgin olive oil, leading to undesirable effects such as accelerated oxidative process and loss of volatile compounds responsible for oil flavor and fragrance. The addition of physical coadjuvants in olive oil processing during the malaxation phase, not excluded by EC regulations owing to its exclusively physical action, is well known to promote the breakdown of oil/water emulsions and consequently make oil extraction easier, thus increasing the yield. Among physical coadjuvants, micronized natural talc is used for olive oil processing above all for Spanish and Italian olive cultivars. The quality of extra virgin olive oil depends on numerous variables such as olive cultivar, ripeness degree and quality, machines utilized for processing, oil storage conditions, etc. However, the coadjuvants utilized in olive processing can also influence virgin olive oil characteristics. The literature highlights an increase in oil yield by micronized natural talc addition during olive processing, whereas no clear trend was observed as regards the chemical, nutritional and sensory characteristics of extra virgin olive oil. Although an increase in oil stability was reported, no effect of talc was found on the evolution of virgin olive oil quality indices during storage. (c) 2016 Society of Chemical Industry. PMID- 26847165 TI - Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 1b study from GELTAMO group. AB - Diffuse large B-cell lymphoma (DLBCL) patients failing rituximab-containing therapy have a poor outcome with the current salvage regimens. We conducted a phase 1b trial to determine the maximum tolerated dose (MTD) of lenalidomide in combination with R-ESHAP (rituximab, etoposide, cisplatin, cytarabine, methylprednisolone) (LR-ESHAP) in patients with relapsed or refractory DLBCL. Efficacy data were collected as a secondary objective. Subjects received 3 cycles of lenalidomide at escalating doses (5, 10 or 15 mg) given on days 1-14 of every 21-day cycle, in combination with R-ESHAP. Responding patients received BEAM (carmustine, etoposide, cytarabine, melphalan) followed by autologous stem-cell transplantation. Lenalidomide 10 mg/d was identified as the MTD because, in the 15 mg cohort, one patient experienced dose-limiting toxicity (grade 3 angioedema) and two patients had mobilization failure. A total of 19 patients (3, 12 and 4 in the 5, 10 and 15 mg cohorts, respectively) were evaluable. All toxicities occurring during LR-ESHAP cycles resolved appropriately and no grade 4-5 non haematological toxicities were observed. The complete remission and overall response rates were 47.4% and 78.9%, respectively. With a median follow-up of 24.6 (17.4-38.2) months, the 2-year progression-free survival and overall survival were 44% and 63%, respectively. In conclusion, the LR-ESHAP regimen is feasible and yields encouraging outcomes. PMID- 26847167 TI - Trends in applying C-H oxidation to the total synthesis of natural products. AB - Covering: 2006 to 2015C-H functionalization remains one of the frontier challenges in organic chemistry and drives quite an active area of research. It has recently been applied in various novel strategies for the synthesis of natural products. It can dramatically increase synthetic efficiency when incorporated into retrosynthetic analyses of complex natural products, making it an essential part of current trends in organic synthesis. In this Review, we focus on selected case studies of recent applications of C-H oxidation methodologies in which the C-H bond has been exploited effectively to construct C O and C-N bonds in natural product syntheses. Examples of syntheses representing different types of C-H oxidation are discussed to illustrate the potential of this approach and inspire future applications. PMID- 26847166 TI - Orthogonal Synthesis of Block Copolymer via Photoinduced CuAAC and Ketene Chemistries. AB - A novel route for the synthesis of poly(ethylene glycol)-b-polystyrene copolymer, starting from commercially available poly(ethylene glycol) methyl ether and azido terminated polystyrene prepared by atom transfer radical polymerization and subsequent nucleophilic substitution, is applied with simplicity and high efficiency. The combination of photoinduced copper (I)-catalyzed alkyne-azide cycloaddition (CuAAC) and ketene chemistry reactions proceeds either simultaneously or sequentially in a one-pot procedure under near-visible light irradiation. In both cases, excellent block copolymer formations are achieved, with an average molecular weight of around 7000 g mo1(-1) and a polydispersity index of 1.20. PMID- 26847168 TI - Effects of different shear rates on the attachment and detachment of platelet thrombi. AB - Thrombosis and hemostasis take place in flowing blood, which generates shear forces. The effect of different shear rates, particularly pathological forces, on platelet thrombus formation remains to be fully elucidated. The present study observed the morphological characteristics and hierarchical structure of thrombi on the collagen surface at a wide range of wall shear rates (WSRs) and examined the underlying mechanisms. Calcein AM-labeled whole blood was perfused over a collagen-coated surface at different shear rates set by a Bioflux 200 microfluidic device and the thrombi formed were assessed for area coverage, the height and the hierarchical structure defined by the extent of platelet activation and packing density. The factors that affect thrombus formation were also investigated. Platelet thrombus formation varied under different WSRs, for example, dispersed platelet adhesion mixed with erythrocytes was observed at 125 250 s(-1), extensive and thin platelet thrombi were observed at 500-1,500 s(-1), and sporadic, thick thrombi were observed at pathological WSRs of 2,500-5,000 s( 1), which showed a tendency to be shed. With increasing WSRs, the height of the thrombi showed an increasing linear trend, whereas the total fluorescence intensity and area of the thrombi exhibited a parabolic curve-like change, with a turning point at a WSR of 2,500 s(-1). The number of thrombi, the average fluorescence intensity and the area per thrombus showed similar trends, with an initial upwards incline followed by a decline. The thrombi formed at higher WSRs had a thicker shell, which led to a more densely packed core. Platelet thrombus formation under shear-flow was regulated by the adhesive strength, which was mediated by receptor-ligand interaction, the platelet deposition induced by shear rates and the detachment by the dynamic force of flow. This resulted in a balance between thrombus attachment, including adhesion and aggregation, and detachment. Collectively, compared with physiological low WSRs, pathological high WSRs caused thicker and more easily shed thrombi with more condensed cores, which was regulated by an attachment-detachment balance. These results provide novel insights into the properties of thrombus formation on collagen at different WSRs, and offers possible explanations for certain clinical physiopathological phenomena, including physical hemostasis and pathological thrombosis. PMID- 26847169 TI - Effect of platform switching on crestal bone levels around implants in the posterior mandible: 3 years results from a multicentre randomized clinical trial. AB - OBJECTIVE: Evaluation of differences in the clinical performance and crestal bone levels between implants restored with single crowns with platform-matched or platform-switched abutments after 3 years. MATERIAL AND METHODS: The study enrolled adult patients missing two or more adjacent teeth in the posterior mandible with natural teeth mesial to the implant site. Randomization followed open-flap implant insertion and the corresponding matching or switching healing abutments placed at surgery. Conventional loading was made with cemented crowns. Clinical follow-up took place annually after loading up to 3 years. Bone level changes were measured in standardized radiographs as the variation in crestal bone from one evaluation to the next. RESULTS: Sixty-three patients with a total of 135 implants (66 platform matching, 69 platform switching) were analysed. From surgery to 36 months, mean bone loss was 0.28 +/- 0.56 mm for the platform switching group and 0.68 +/- 0.64 mm for the platform-matching group. A statistically significant difference was found between groups (p = 0.002) with an estimate of 0.39 mm (0.15-0.64, 95% CI) in favour of platform switching. CONCLUSIONS: After 3 years, platform-switching restorations showed a significant effect in the preservation of marginal bone levels compared to platform-matching restorations. PMID- 26847171 TI - Dermoscopy and Reflectance Confocal Microscopy for Monitoring the Treatment of Actinic Keratosis with Ingenol Mebutate Gel: Report of Two Cases. AB - INTRODUCTION: A relatively novel application for dermoscopy and reflectance confocal microscopy (RCM) is their use in the monitoring of topical treatment response for non-melanoma skin cancer. Actinic keratosis (AK) is the early phase of a multistep biologic continuum leading to invasive squamous cell carcinoma. A number of topical therapies are now available for the treatment of AK but their disadvantages include long treatment duration and prolonged local reactions. Ingenol mebutate is a newer therapy for AK which is only applied for 2 or 3 days. CASE REPORT: Dermoscopy and RCM findings in two patients with AK treated with ingenol mebutate confirm that it induces rapid lesion necrosis and specific neutrophil-mediated, antibody-dependent cellular cytotoxicity. Necrosis occurs via mitochondrial membrane disruption, with subsequent eradication of residual tumor cells via transient inflammation. Local skin reactions to ingenol mebutate should be considered part of the drug's mechanism of action rather than an adverse effect. CONCLUSION: Ingenol mebutate is a valuable therapy for the treatment of AK. This case report adds further evidence to the usefulness of dermoscopy and RCM in the assessment and monitoring of treatment outcome. PMID- 26847170 TI - Diosmetin inhibits the metastasis of hepatocellular carcinoma cells by downregulating the expression levels of MMP-2 and MMP-9. AB - Hepatocellular carcinoma (HCC) is one of the most malignant types of tumor worldwide with a high rate of mortality. Diosmetin (DIOS) exhibits various activities, including anticancer activities. However, the role of DIOS in the metastasis of HCC, and its underlying molecular mechanism, remain to be fully elucidated. In the present study, the antimetastatic effects of DIOS were investigated in SK-HEP-1 and MHcc97H HCC cell lines. Cell proliferation, wound healing, motility, invasion and adhesion capacities were examined to evaluate the inhibitory effect of DIOS on the metastasis of HCC cells. Cell viability was detected using an MTT assay in order to verify the inhibitory effect of DIOS on the proliferation of HCC cells. Cell migration was assessed using would healing and motility assays in order to verify the inhibitory effect of DIOS on the migration of HCC cells. Cell invasion and adhesion assays were performed in order to verify the inhibitory effect of DIOS on the invasion and adhesion of HCC cells. Matrix metalloproteinase (MMP)-2/9, proteins of the mitogen-activated protein kinase (MAPK) pathway (c-Jun N-terminal kinase, extracellular signal regulated kinase and p38 MAPK) and protein kinase C-delta were detected in order to verify the potential molecular mechanisms of DIOS in the inhibition of the metastasis of HCC cells. DIOS was observed to inhibit the metastasis of SK-HEP-1 and MHcc97H cells by downregulating the expression of MMP-2/9 via the PKC/MAPK/MMP pathways. DIOS also inhibited the migration and invasion of the HCC cells, and may serve as a potential candidate agent for the prevention of HCC metastasis. PMID- 26847172 TI - Acid Treatment Enables Suppression of Electron-Hole Recombination in Hematite for Photoelectrochemical Water Splitting. AB - We report a strategy for efficient suppression of electron-hole recombination in hematite photoanodes. Acid-treated hematite showed a substantially enhanced photocurrent density compared to untreated samples. Electrochemical impedance spectroscopy studies revealed that the enhanced photocurrent is partly due to improved efficiency of charge separation. Transient absorption spectroscopic studies coupled to electrochemical measurements indicate that, in addition to improved bulk electrochemical properties, acid-treated hematite has significantly decreased surface electron-hole recombination losses owing to a greater yield of the trapped photoelectrons being extracted to the external circuit. PMID- 26847173 TI - Identification of microRNA expression profile related to lymph node status in women with early-stage grade 1-2 endometrial cancer. AB - Conventional methods used for histologic classification and grading of endometrial cancer (EC) are not sufficient to predict lymph node metastases. microRNA signatures have recently been related to EC pathologic characteristics or prognosis. The aim of this study was to evaluate whether microRNA profiles of grade 1-2 endometrioid adenocarcinomas can be related to nodal status and used as a tool to adapt surgical staging in early-stage EC. microRNA expression was assessed in nine formalin-fixed paraffin-embedded (FFPE) EC primary tumors with positive lymph node and in 27 FFPE EC primary tumors with negative lymph node, matched for grade, stage, and lymphovascular space involvement status. A microarray analysis showed that there was more than a twofold significant difference in the expression of 12 microRNAs between the two groups. A quantitative reverse transcriptase-PCR assay was used to confirm these results: the expression levels of five microRNAs (microRNA-34c-5p, -375, -184, -34c-3p, and -34b-5p) were significantly lower in the EC primary tumor with positive lymph node compared with those with negative lymph node. A minimal P-value approach revealed that women with a microRNA-375-fold change <0.30 were more likely to have positive lymph node (n=8; 53.3%) compared with those with a microRNA-375 fold change >0.30 (n=1; 4.8%), P=0.001. Furthermore, women with a microRNA 184 fold change <0.30 were more likely to have positive lymph node (n=6; 60.0%) compared with those with a microRNA 184-fold change >0.30 (n=3; 11.5%), P=0.006. This is the first study investigating the relative expression of mature microRNA genes in early-stage grade 1-2 EC primary tumors according to the nodal status. This microRNA expression profile provides a potential basis for further study of the microRNA function in EC and could be used as a diagnostic tool for nodal status. PMID- 26847174 TI - THSD7A staining of membranous glomerulopathy in clinical practice reveals cases with dual autoantibody positivity. AB - Thrombospondin type I domain-containing 7A (THSD7A) is a known antigenic target of autoantibodies leading to primary membranous glomerulopathy and was reported to account for ~10% of phospholipase A2 receptor (PLA2R)-negative membranous glomerulopathy. It has been proposed that PLA2R and THSD7A autoantibodies are mutually exclusive in membranous glomerulopathy. We validated an immunohistochemical assay to investigate for THSD7A-associated membranous glomerulopathy and utilized it in 258 consecutive native kidney biopsies, which showed membranous glomerulopathy in our laboratory, with the exception of membranous lupus nephritis. Membranous glomerulopathy stained positive for THSD7A only in 7 (3%) cases, PLA2R-only in 141 (55%) cases, and showed dual positivity for THSD7A and PLA2R in 2 (1%) cases. Serologic testing for antibodies to PLA2R and THSD7A was performed in a subset of these patients. There was 100% correlation between positive THSD7A and/or PLA2R tissue staining and the presence of the corresponding autoantibodies in the serum including the two cases with dual positive THSD7A and PLA2R antibodies. We describe and provide a protocol for detection of THSD7A-associated membranous glomerulopathy in clinical practice. The cases with dual THSD7A and PLA2R positivity show that these autoantibodies are not mutually exclusive. They also emphasize the importance of using a panel based approach when subtyping membranous glomerulopathy as a patient could conceptually be identified and treated based on anti-PLA2R titers, but still have anti-THSD7A antibodies driving persistent disease. PMID- 26847175 TI - Evaluation of NKX2-2 expression in round cell sarcomas and other tumors with EWSR1 rearrangement: imperfect specificity for Ewing sarcoma. AB - Ewing sarcoma shows considerable histologic overlap with other round cell tumors. NKX2-2, a homeodomain transcription factor involved in neuroendocrine/glial differentiation and a downstream target of EWSR1-FLI1, has been reported as an immunohistochemical marker for Ewing sarcoma. We assessed the specificity of NKX2 2 for Ewing sarcoma compared with other round cell malignant neoplasms and other soft tissue tumors with EWSR1 translocations. We evaluated whole-tissue sections from 270 cases: 40 Ewing sarcomas (4 with atypical/large cell features), 20 CIC DUX4 sarcomas, 5 BCOR-CCNB3 sarcomas, 9 unclassified round cell sarcomas, 10 poorly differentiated synovial sarcomas, 10 lymphoblastic lymphomas, 10 alveolar rhabdomyosarcomas, 10 embryonal rhabdomyosarcomas, 10 Merkel cell carcinomas, 10 small cell carcinomas, 20 melanomas, 5 NUT midline carcinomas, 10 Wilms tumors, 10 neuroblastomas, 10 olfactory neuroblastomas, 12 mesenchymal chondrosarcomas, 10 angiomatoid fibrous histiocytomas, 10 clear cell sarcomas, 5 gastrointestinal clear cell sarcoma-like tumors, 5 desmoplastic small round cell tumors, 10 extraskeletal myxoid chondrosarcomas, 10 soft tissue and cutaneous myoepitheliomas, and 19 myoepithelial carcinomas. NKX2-2 positivity was defined as moderate-to-strong nuclear immunoreactivity in at least 5% of cells. NKX2-2 was positive in 37/40 (93%) Ewing sarcomas, including all atypical Ewing sarcomas and cases with known EWSR1-FLI1 or EWSR1-ERG fusion; 85% of Ewing sarcomas showed diffuse (>50%) staining. NKX2-2 was positive in 9 (75%) mesenchymal chondrosarcomas, 8 (80%) olfactory neuroblastomas, 1 CIC-DUX4 sarcoma, 1 poorly differentiated synovial sarcoma, 1 neuroblastoma, 2 unclassified round cell sarcomas, and 3 small cell carcinomas; all other EWSR1-associated tumors were negative for NKX2-2, apart from 1 desmoplastic small round cell tumor, 1 myoepithelioma, and 1 myoepithelial carcinoma. In summary, NKX2-2 is a sensitive but imperfectly specific marker for Ewing sarcoma. Nonetheless, NKX2-2 may be helpful to distinguish Ewing sarcoma from some histologic mimics including CIC DUX4 and BCOR-CCNB3 sarcomas. Most other EWSR1-associated soft tissue tumors are negative for NKX2-2. PMID- 26847176 TI - Characterization of the enhancer element of the Danio rerio minor globin gene locus. AB - In Danio rerio, the alpha- and beta-globin genes are present in two clusters: a major cluster located on chromosome 3 and a minor cluster located on chromosome 12. In contrast to the segregated alpha- and beta-globin gene domains of warm blooded animals, in Danio rerio, each cluster contains both alpha- and beta globin genes. Expression of globin genes present in the major cluster is controlled by an erythroid-specific enhancer similar to the major regulatory element of mammalian and avian alpha-globin gene domains. The enhancer controlling expression of the globin genes present in the minor locus has not been identified yet. Based on the distribution of epigenetic marks, we have selected two genomic regions that might harbor an enhancer of the minor locus. Using transient transfection of constructs with a reporter gene, we have demonstrated that a ~500-bp DNA fragment located ~1.7 Kb upstream of the alphae4 gene possesses an erythroid-specific enhancer active with respect to promoters present in both the major and the minor globin gene loci of Danio rerio. The identified enhancer element harbors clustered binding sites for GATA-1, NF-E2, and EKLF similar to the enhancer of the major globin locus on chromosome 3. Both enhancers appear to have emerged as a result of independent evolution of a duplicated regulatory element present in an ancestral single alpha-/beta-globin locus that existed before teleost-specific genome duplication. PMID- 26847177 TI - Morphology of nuclear transcription. AB - Gene expression control is a fundamental determinant of cellular life with transcription being the most important step. The spatial nuclear arrangement of the transcription process driven by RNA polymerases II and III is nonrandomly organized in foci, which is believed to add another regulatory layer on gene expression control. RNA polymerase I transcription takes place within a specialized organelle, the nucleolus. Transcription of ribosomal RNA directly responds to metabolic requirements, which in turn is reflected in the architecture of nucleoli. It differs from that of the other polymerases with respect to the gene template organization, transcription rate, and epigenetic expression control, whereas other features are shared like the formation of DNA loops bringing genes and components of the transcription machinery in close proximity. In recent years, significant advances have been made in the understanding of the structural prerequisites of nuclear transcription, of the arrangement in the nuclear volume, and of the dynamics of these entities. Here, we compare ribosomal RNA and mRNA transcription side by side and review the current understanding focusing on structural aspects of transcription foci, of their constituents, and of the dynamical behavior of these components with respect to foci formation, disassembly, and cell cycle. PMID- 26847181 TI - Tools for visualization of phosphoinositides in the cell nucleus. AB - Phosphoinositides (PIs) are glycerol-based phospholipids containing hydrophilic inositol ring. The inositol ring is mono-, bis-, or tris-phosphorylated yielding seven PIs members. Ample evidence shows that PIs localize both to the cytoplasm and to the nucleus. However, tools for direct visualization of nuclear PIs are limited and many studies thus employ indirect approaches, such as staining of their metabolic enzymes. Since localization and mobility of PIs differ from their metabolic enzymes, these approaches may result in incomplete data. In this paper, we tested commercially available PIs antibodies by light microscopy on fixed cells, tested their specificity using protein-lipid overlay assay and blocking assay, and compared their staining patterns. Additionally, we prepared recombinant PIs-binding domains and tested them on both fixed and live cells by light microscopy. The results provide a useful overview of usability of the tools tested and stress that the selection of adequate tools is critical. Knowing the localization of individual PIs in various functional compartments should enable us to better understand the roles of PIs in the cell nucleus. PMID- 26847182 TI - The diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography and computed tomography in staging bladder cancer: a single-institution study and a systematic review with meta-analysis. AB - PURPOSE: The purpose of this study was to assess the diagnostic accuracy of 18F fluorodeoxyglucose with positron emission tomography and computed tomography (FDG PET-CT) to predict nodal metastases in patients with bladder cancer (BC) scheduled to undergo radical cystectomy (RC). METHODS: We retrospectively reviewed records of patients diagnosed with BC and scheduled to undergo RC at our center from January 2011 through February 2015, who also underwent FDG-PET-CT at the time of diagnosis. All patients underwent RC and an extended pelvic lymph node dissection as the reference standard. The primary endpoints were the sensitivity, specificity and overall accuracy of FDG-PET-CT in detecting lymph node metastasis. We also examined its accuracy in identifying distant metastasis. In addition, we conducted a protocol-driven systematic review and meta-analysis of accuracy of FDG-PET-CT for preoperative staging of BC, as compared to CT alone, as reported in individual studies. To assess the methodological quality of eligible studies, we used the QUADAS-2 tool (a revised tool for the Quality Assessment of Diagnostic Accuracy Studies) and pooled diagnostic accuracy measures using Meta-DiSc statistical software. RESULTS: For detecting nodal metastases in 78 patients, the sensitivity of FDG-PET-CT was 0.56 (95 % CI 0.29 0.80) and the specificity, 0.98 (95 % CI 0.91-1.00). Pooled sensitivity and specificity for detecting lymph node metastasis were 0.57 and 0.95, respectively. Positive likelihood ratio was 9.02. All lesions that were suspicious for distant metastasis were found to be positive on biopsy. CONCLUSION: FDG-PET-CT was more accurate than CT alone in staging BC in patients undergoing surgery. Standardization of FDG-PET-CT protocol and cost-effectiveness analysis are required before widespread implementation of this technology. PMID- 26847178 TI - Nucleolar DNA: the host and the guests. AB - Nucleoli are formed on the basis of ribosomal genes coding for RNAs of ribosomal particles, but also include a great variety of other DNA regions. In this article, we discuss the characteristics of ribosomal DNA: the structure of the rDNA locus, complex organization and functions of the intergenic spacer, multiplicity of gene copies in one cell, selective silencing of genes and whole gene clusters, relation to components of nucleolar ultrastructure, specific problems associated with replication. We also review current data on the role of non-ribosomal DNA in the organization and function of nucleoli. Finally, we discuss probable causes preventing efficient visualization of DNA in nucleoli. PMID- 26847183 TI - 3D NavigoTM versus TRUS-guided prostate biopsy in prostate cancer detection. AB - INTRODUCTION: To overcome the limitations regarding transrectal ultrasound (TRUS) guided biopsies in prostate cancer (PCa) detection, there is a focus on new imaging technologies. The NavigoTM system (UC-care, Israel) uses regular TRUS images and electrospatial monitoring to generate a 3D model of the prostate. The aim of this study was to compare cancer detection rates between the NavigoTM system and conventional TRUS, in patients without a history of PCa. METHODS: We performed a retrospective study by collecting data from all patients who underwent 12-core prostate biopsies from lateral peripheral zones between September 2013 and February 2015 at the Jeroen Bosch Hospital in 's-Hertogenbosch (Netherlands). RESULTS: A total of 325 patients met our inclusion criteria. 77.8 % of biopsy sessions were performed using the NavigoTM system. There was no statistically significant difference in PCa detection (39.9 vs 46.2 % with NavigoTM system and TRUS, respectively). Using the NavigoTM system for taking prostate biopsies proved not to be associated with the presence of PCa at biopsy, likewise for clinically significant PCa and for both subgroups. LIMITATIONS: The limitations of the study include its retrospective design, the limited number of patients in the conventional TRUS group, the statistically significant different number of biopsy sessions and the ones performed by an advanced physician in both groups. CONCLUSION: In our study, there is no added value of 3D TRUS using NavigoTM system compared to conventional 2D TRUS regarding PCa detection in biopsy-naive men and men with prior negative biopsy. PMID- 26847184 TI - Clinical features and prognosis of elderly patients with hepatocellular carcinoma not indicated for surgical resection. AB - Hepatocellular carcinoma (HCC) is a major health problem worldwide. The average life expectancy during the 20th century has increased in many parts of the world, and therefore the opportunities to examine elderly HCC patients have significantly increased worldwide. Many elderly patients develop HCC with intermediate to advanced stages of disease at the initial diagnosis, and have more comorbidities and compromised liver regeneration compared with younger patients. These circumstances show that elderly patients with HCC are poorer candidates for surgical resection or transplantation. The aim of the present review was to focus on the clinical features and prognosis of elderly HCC patients not indicated for surgical resection including multimodal treatment. Although the chronological age of 60 or 65 years as the definition of an elderly person is accepted in most countries, many studies in our review article define elderly as those aged 75 years or older. Geriatr Gerontol Int 2017; 17: 189-201. PMID- 26847179 TI - Actin, actin-binding proteins, and actin-related proteins in the nucleus. AB - Extensive research in the past decade has significantly broadened our view about the role actin plays in the life of the cell and added novel aspects to actin research. One of these new aspects is the discovery of the existence of nuclear actin which became evident only recently. Nuclear activities including transcriptional activation in the case of all three RNA polymerases, editing and nuclear export of mRNAs, and chromatin remodeling all depend on actin. It also became clear that there is a fine-tuned equilibrium between cytoplasmic and nuclear actin pools and that this balance is ensured by an export-import system dedicated to actin. After over half a century of research on conventional actin and its organizing partners in the cytoplasm, it was also an unexpected finding that the nucleus contains more than 30 actin-binding proteins and new classes of actin-related proteins which are not able to form filaments but had evolved nuclear-specific functions. The actin-binding and actin-related proteins in the nucleus have been linked to RNA transcription and processing, nuclear transport, and chromatin remodeling. In this paper, we attempt to provide an overview of the wide range of information that is now available about actin, actin-binding, and actin-related proteins in the nucleus. PMID- 26847180 TI - Molecular insights into the premature aging disease progeria. AB - Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare premature aging disease presenting many features resembling the normal aging process. HGPS patients die before the age of 20 years due to cardiovascular problems and heart failure. HGPS is linked to mutations in the LMNA gene encoding the intermediate filament protein lamin A. Lamin A is a major component of the nuclear lamina, a scaffold structure at the nuclear envelope that defines mechanochemical properties of the nucleus and is involved in chromatin organization and epigenetic regulation. Lamin A is also present in the nuclear interior where it fulfills lamina-independent functions in cell signaling and gene regulation. The most common LMNA mutation linked to HGPS leads to mis-splicing of the LMNA mRNA and produces a mutant lamin A protein called progerin that tightly associates with the inner nuclear membrane and affects the dynamic properties of lamins. Progerin expression impairs many important cellular processes providing insight into potential disease mechanisms. These include changes in mechanosignaling, altered chromatin organization and impaired genome stability, and changes in signaling pathways, leading to impaired regulation of adult stem cells, defective extracellular matrix production and premature cell senescence. In this review, we discuss these pathways and their potential contribution to the disease pathologies as well as therapeutic approaches used in preclinical and clinical tests. PMID- 26847185 TI - Lux-operon of the Marine Psychrophilic Bacteria Aliivibrio logei: a Comparative Analysis of the LuxR1/LuxR2 Regulatory Activity in Escherichia coli cells. AB - The lux-operon of the psychrophilic bioluminescent bacterium A. logei is regulated by Quorum Sensing (QS). The key components of this system are LuxI that catalyzes the synthesis of autoinducer (AI) and LuxR that activates the transcription of entire lux-operon. The lux-operon of A. logei contains two copies of luxR gene: luxR1 and luxR2. In the present study lux-operon sequence analysis from 16 strains of A. logei, isolated from cold habitats of the White, Baltic, Okhotsk and Bering Seas was carried out. The phylogenetic analysis showed that all isolated strains of A. logei have both copies of luxR genes which are homologous to luxR genes of relative A. salmonicida. LuxR1 and LuxR2 activity evaluation showed that LuxR2 remain active at significantly lower concentration of AI (10-9M) compared to LuxR1 which is activate only at high AI concentration (10-6M). As QS response is already prominent at AI concentrations as low as 10-8 10-9M, we conclude that LuxR2 is a main activator of the lux-operon of A. logei. The thermolabilities of LuxR1 and LuxR2 are similar and exceed that of LuxR of mesophilic bacterium A. fischeri. As oppose to LuxR2, LuxR1 is not a substrate of Lon protease and does not require the chaperonin GroEL/ES for its folding. PMID- 26847188 TI - Assessment of diffusion parameters of new passive samplers using optical chemical sensor for on-site measuring formaldehyde in indoor air: experimental and numerical studies. AB - New passive samplers using a sensor consisting of a sol-gel matrix entrapping Fluoral-P as sampling media were developed for the determination of formaldehyde in indoor air. The reaction between Fluoral-P and formaldehyde produces a colored compound which is quantified on-site by means of a simple optical reading module. The advantages of this sensor are selectivity, low cost, ppb level limit of detection, and on-site direct measurement. In the development process, it is necessary to determine the sampling rate, a key parameter that cannot be directly assessed in the case of diffusive samplers using optical chemical sensor. In this study, a methodology combining experimental tests and numerical modeling is proposed and applied at five different radial diffusive samplers equipped with the same optical chemical sensor to assess the sampled material flows and sampling rates. These radial diffusive samplers differ in the internal volume of the sampler (18.97 and 6.14 cm(3)), the position of sensor inside the sampler (in front and offset of 1.2 cm above the membrane) and the width of the diffusion slot (1.4 and 5.9 mm). The influences of these three parameters (internal volume, position of sensor inside the sampler, and width of the diffusion slot) were assessed and discussed with regard to the formaldehyde sampling rate and water uptake by sensor (potential interference of measure). Numerical simulations based on Fick's laws are in agreement with the experimental results and provide to estimate the effective diffusion coefficient of formaldehyde through the membrane (3.50 * 10(-6) m(2) s(-1)). Conversion factors between the sensor response, sampled formaldehyde mass and sampling rate were also assessed. PMID- 26847187 TI - New Horizons for the Study of Dietary Fiber and Health: A Review. AB - Dietary fibre has been consumed for centuries with known health benefits, but defining dietary fibre is a real challenge. From a functional perspective, dietary fibre is described as supporting laxation, attenuating blood glucose responses and assisting with cholesterol lowering. The problem is different types of dietary fibre have different effects, and new effects are increasingly observed, such as the influence on gut microbiota. Thus, a single definition may need to be described in more generic terms. Rather than being bound by a few functional definitions, we may need to embrace the possibilities of new horizons, and derive a working definition of dietary fibre based on a set of conceptual principles, rather than the limited definitions we have to date. To begin this process, a review of individual fibre types and their physiological effects would be helpful. Dietary fibre is a complex group of substances, and there is a growing interest in specific effects linked to fibre type. Different fractions of dietary fibre have different physiological properties, yet there is a paucity of literature covering the effects of all fibres. This paper describes a range of individual fibre types and identifies gaps in the literature which may expose new directions for a working definition of dietary fibre. PMID- 26847186 TI - Activated mast cells promote differentiation of B cells into effector cells. AB - Based on the known accumulation of mast cells (MCs) in B cell-dependent inflammatory diseases, including rheumatoid arthritis, we hypothesized that MCs directly modulate B cells. We show here that degranulated, and to a lesser extent naive or IgE-sensitized, MCs activate both naive and B cell receptor-activated B cells. This was shown by increased proliferation, blast formation, and expression of CD19, MHC class II and CD86 in the B cells. Further, MCs stimulated the secretion of IgM and IgG in IgM(+) B cells, indicating that MCs can induce class switch recombination in B cells. We also show that coculture of MCs with B cells promotes surface expression of L-selectin, a homing receptor, on the B cells. The effects of MCs on B cells were partly dependent on cell-cell contact and both follicular and marginal zone B cells could be activated by MCs. Our findings suggest that degranulated MCs support optimal activation of B cells, a finding that is in line with in vivo studies showing that MCs frequently degranulate in the context of B-cell driven pathologies such as arthritis. Together, our findings show that MCs have the capacity to differentiate B cells to effector cells. PMID- 26847189 TI - Detection of low-quantity anticancer drugs by surface-enhanced Raman scattering. AB - Ultrasensitive detection of low-quantity drugs is important for personalized therapeutic approaches in several diseases and, in particular, for cancer treatment. In this field, surface-enhanced Raman scattering (SERS) can be very useful for its ability to precisely identify analytes from their unique vibrational spectra, with very high sensitivity. Here, we report a study about SERS detection of sunitinib, paclitaxel and irinotecan, i.e. three commonly used antineoplastic drugs, and of SN-38, i.e. the metabolite of irinotecan, dissolved in methanol solutions. By using commercial Klarite substrates, we found that sunitinib, irinotecan and SN-38 have detection limits of 20-70 ng, which is below the threshold for applications in cancer therapy. Conversely, the SERS signal was not appreciable with paclitaxel, and this is explained by the absence of optical resonances in the visible range. Overall, our results show that ultrasensitive SERS detection of sunitinib, irinotecan and SN-38 is feasible, encouraging further development of this technology also for other drugs with similar molecular structure especially for those analytes with absorption bands in the visible range. PMID- 26847190 TI - Combining single-particle inductively coupled plasma mass spectrometry and X-ray absorption spectroscopy to evaluate the release of colloidal arsenic from environmental samples. AB - Detection and sizing of natural colloids involved in the release and transport of toxic metals and metalloids is essential to understand and model their environmental effects. Single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS) was applied for the detection of arsenic-bearing particles released from mine wastes. Arsenic-bearing particles were detected in leachates from mine wastes, with a mass-per-particle detection limit of 0.64 ng of arsenic. Conversion of the mass-per-particle information provided by SP-ICP-MS into size information requires knowledge of the nature of the particles; therefore, synchrotron-based X-ray absorption spectroscopy (XAS) was used to identify scorodite (FeAsO4.2H2O) as the main species in the colloidal particles isolated by ultrafiltration. The size of the scorodite particles detected in the leachates was below 300-350 nm, in good agreement with the values obtained by TEM. The size of the particles detected by SP-ICP-MS was determined as the average edge of scorodite crystals, which show a rhombic dipyramidal form, achieving a size detection limit of 117 nm. The combined use of SP-ICP-MS and XAS allowed detection, identification, and size determination of scorodite particles released from mine wastes, suggesting their potential to transport arsenic. Graphical abstract Analytical approach for the detection and size characterization of As-bearing particles by SP-ICP-MS and XAS in environmental samples. PMID- 26847191 TI - Spherical silver nanoparticles in the detection of thermally denatured collagens. AB - We have developed a rapid colorimetric method to determine the concentration of denatured collagen in solution, which is based on the collagen-silver nanoparticle corona formation. Using the proposed method, the lowest detectable concentration of denatured collagen protein in a solution of pure collagen was 14.7, 8.5, and 8.6 MUg mL(-1) for porcine (PCOL), rat tail (RCOL), and type I human recombinant (HCOL) collagen, respectively. PMID- 26847192 TI - Muller-Weiss Syndrome: Radiological Features and the Role of Weightbearing Computed Tomography Scan. AB - Muller-Weiss disease (MWD) is a rare condition that results in dorsolateral collapse of the navicular associated with rotation of the talar head and subtalar varus deformity. There are also varying degrees of midfoot collapse and associated loss of the medial arch in more advanced cases. The characteristic deformities and classification have been described on weightbearing radiographs. While early stage disease can be detected on magnetic resonance imaging and bone scan, there are considerable advantages to computed tomography (CT) scanning, in particular, weightbearing CT for further evaluation of this condition. We describe the imaging findings of this condition, and present 3 cases where weightbearing CT was used in the context of MWD. This is the first time the use of weightbearing CT scan has been reported for diagnosis and treatment of this condition. LEVELS OF EVIDENCE: Diagnostic, Level IV: Case series. PMID- 26847193 TI - A Closed Lateral Subtalar Dislocation With Checkrein Deformity of Great Toe due to Entrapment of Flexor Hallucis Longus: A Case Report. AB - Closed lateral subtalar dislocation is a very rare injury. We report a case of closed lateral subtalar dislocation with entrapment of flexor hallucis longus tendon producing a checkrein deformity. The patient was managed immediately with closed reduction under regional anesthesia and fixated with percutaneous Kirschner wires. Early mobilization and weightbearing was started and there were no complications till the last follow-up visit. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case study. PMID- 26847194 TI - An Isolated Chronic Osteochondral Fracture of the Third Metatarsal Head Treated With Bioabsorbable Pins: A Case Report. AB - : An osteochondral fracture of the metatarsal head is generally the result of direct trauma and is associated with additional proximal fractures of the medially adjacent metatarsals. An isolated osteochondral fracture of the metatarsal head is extremely rare, with only 10 published case reports. Open reduction and internal fixation was performed in 6 of 10 cases and in 2 of 4 chronic cases, each with different implants previously. The mechanism of injury was considered to be shear force in 5 of the reported cases. It is difficult to achieve and maintain reduction in these cases, and the best method for treatment of this type of fracture is unclear. We report a case of an isolated chronic osteochondral fracture of the third metatarsal head in a 14-year-old boy. The boy reported pain in his third metatarsophalangeal joint on dismounting from a bicycle 2 months prior to presentation. He could play soccer at first; however, the pain worsened after running long distances. Therefore, he was referred to our department. Magnetic resonance imaging revealed an osteochondral fracture of the metatarsal head without Freiberg's disease. We achieved a good result 12 months postoperatively by using open reduction and internal fixation with 2 bioabsorbable thread pins. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case study. PMID- 26847195 TI - Assessment of brain temperatures during different phases of the menstrual cycle using diffusion-weighted imaging thermometry. AB - PURPOSE: To investigate changes in brain temperature according to the menstrual cycle in women using diffusion-weighted imaging (DWI) thermometry and to clarify relationships between brain and body temperatures. MATERIALS AND METHODS: In 20 healthy female volunteers (21.3-38.8 years), DWI of the brain was performed during the follicular and luteal phases to calculate the brain temperature. During DWI, body temperatures were also measured. Group comparisons of each temperature between the two phases were performed using the paired t test. Correlations between brain and body temperatures were analyzed using Pearson's correlation coefficient test. RESULTS: Mean diffusion-based brain temperature was 36.24 degrees C (follicular) and 36.96 degrees C (luteal), showing a significant difference (P < 0.0001). Significant differences were also seen for each body temperature between the two phases. Correlation coefficients between diffusion-based brain and each body temperature were r = 0.2441 (P = 0.1291), 0.0332 (0.8387), and -0.0462 (0.7769), respectively. CONCLUSIONS: In women of childbearing age, brain and body temperatures appear significantly higher in the luteal than in the follicular phase. However, brain and body temperatures show no significant correlations. PMID- 26847196 TI - Young male sex workers are at high risk for sexually transmitted infections, a cross-sectional study from Dutch STI clinics, the Netherlands, 2006-2012. AB - BACKGROUND: Male sex workers (MSW) are particularly exposed to sexually transmitted infections (STI) including HIV. In the Netherlands, data about STI among MSW are scarce. We estimated chlamydia, gonorrhoea, syphilis and HIV diagnoses among MSW attending STI clinics and determined associated factors to guide prevention policies. METHODS: Using 2006-2012 cross-sectional national surveillance data from Dutch STI clinics, we calculated the proportion of consultations with a positive test for any of three bacterial STI or HIV among MSW. Associated factors were determined by using Poisson logistic regression with robust variance. RESULTS: We identified 3,053 consultations involving MSW, of which 18.1 % included at least one positive bacterial STI test and 2.5 % a positive HIV test. Factors associated with bacterial STI and/or HIV diagnoses were respectively age groups < 35 y.o. and self-reporting homo- or bisexual preferences (aRR = 1.6; 95 % CI: 1.3-2.1), and age group 25-34 y.o. (aRR = 2.7; 95 % CI: 1.2-6.5) and self-reporting homo- or bisexual preferences (aRR = 24.4; 95 % CI: 3.4-176.9). Newly diagnosed and pre-existing HIV infection were associated with an increased risk for bacterial STI (aRR = 2.7, 95 % CI: 1.7-2.6 and aRR = 2.1, 95 % CI: 2.2-3.4 respectively). MSW with no history of HIV screening were more likely to be tested positive for HIV compared to those with a previous HIV-negative test (aRR = 2.6, 95 % CI: 1.6-4.3). CONCLUSION: Health promotion activities should target MSW who are young, homo- or bisexual, those who are HIV-infected or who have never been tested for HIV, to increase early diagnosis, prevention and treatment. PMID- 26847197 TI - Association of PNPLA3 rs738409 and TM6SF2 rs58542926 with health services utilization in a population-based study. AB - BACKGROUND: Hepatic steatosis confers an increased risk of metabolic and cardiovascular disease and higher health services use. Associations of the single nucleotide polymorphisms (SNP) PNPLA3 rs738409 and TM6SF2 rs58542926 with hepatic steatosis have recently been established. This study investigates the association between rs738409 and rs58542926 with health services utilization in a general population. METHODS: Data of 3759 participants from Study of Health in Pomerania (SHIP), a population-based study in Germany, were obtained. The annual number of outpatient visits, hospitalization and length of hospital stay was regressed on rs738409 and rs58542926 and adjusted for socio-economic factors, lifestyle habits, clinical factors, and health status. RESULTS: Minor allele homozygous subjects of rs738409 had an increased odds of hospitalization as compared to major allele homozygous subjects (odds ratio [OR] 1.51; 95% confidence interval [CI], 1.02 to 2.15). Heterozygous subjects did not differ from major allele homozygous subjects with respect to their odds of hospitalization. The three genotype groups of rs738409 were similar with respect to the number of outpatient visits and inpatient days. Minor allele homozygous and heterozygous subjects of rs58542926 had higher outpatient utilization (+53.04% and +67.56%, p < 0.05, respectively) and inpatient days than major allele homozygous subjects. CONCLUSIONS: After adjustment for several confounding factors, PNPLA3 rs738409 and TM6SF2 rs58542926 were associated with the number of outpatient visits, hospitalization, and inpatient days. Further studies are warranted to replicate our findings and to evaluate whether genetic data can be used to identify subjects with excess health services utilization. PMID- 26847198 TI - Babesia caballi and Theileria equi infections in horses in Central-Southern Italy: Sero-molecular survey and associated risk factors. AB - Babesia caballi and Theileria equi are tick-borne pathogens, etiological agents of equine piroplasmosis that affect different species of Equidae causing relevantly important direct and indirect losses. A field study was conducted to evaluate the distribution of the equine piroplasms in an area of Central-Southern Italy and to identify correlated risk factors. Serum samples of 673 asymptomatic horses were collected during spring-summer of 2013 to estimate the seroprevalence of the parasites within the study area using T. equi and B. caballi Antibody test kit (VMRD((r)), Inc, Pullman, WA, USA). The 273 seropositive samples were subsequently tested by real time PCR to verify the presence of the genome of the piroplasms, indicative of the carrier status of the subjects. The variables chosen to identify which were the risk factors associated with the serological and PCR-positivity for each of the equine piroplasms were the following: gender, age, breed, access to pasture, altitude, land cover, climatic zone, soil type and province location (coastal/inland). The resulting overall seroprevalence for T. equi was 39.8% (268/673) and for B. caballi was 8.9% (60/673) while 70.3% of the PCR tested samples (185/263) were positive for T. equi and 10.3% (27/263) for B. caballi. The univariate and multiple logistic regression models were used to assess the association of the risk factors with the different outcomes. The risk factors found to be associated with T. equi seropositivity were gender, age, breed, access to pasture, land cover, soil type and province location, while those associated with PCR-positivity were age, soil type and province location. As the number of B. caballi seropositive subjects was limited, the multiple logistic regression model was performed only for the PCR-positive status, identifying climatic zone and soil type as the sole risk factors. In the study area, a major diffusion of T. equi, in terms of seroprevalence and PCR-positivity was present when compared to that of B. caballi, probably related to the cumulative effect of the life-long infection of the former protozoan. The identification of risk factors relative to each piroplasm infection, specific to a study area, is important in the development and improvement of tailored control and prevention programmes aimed at containing health and economic consequences. PMID- 26847200 TI - DNA Gyrase of Deinococcus radiodurans is characterized as Type II bacterial topoisomerase and its activity is differentially regulated by PprA in vitro. AB - The multipartite genome of Deinococcus radiodurans forms toroidal structure. It encodes topoisomerase IB and both the subunits of DNA gyrase (DrGyr) while lacks other bacterial topoisomerases. Recently, PprA a pleiotropic protein involved in radiation resistance in D. radiodurans has been suggested for having roles in cell division and genome maintenance. In vivo interaction of PprA with topoisomerases has also been shown. DrGyr constituted from recombinant gyrase A and gyrase B subunits showed decatenation, relaxation and supercoiling activities. Wild type PprA stimulated DNA relaxation activity while inhibited supercoiling activity of DrGyr. Lysine133 to glutamic acid (K133E) and tryptophane183 to arginine (W183R) replacements resulted loss of DNA binding activity in PprA and that showed very little effect on DrGyr activities in vitro. Interestingly, wild type PprA and its K133E derivative continued interacting with GyrA in vivo while W183R, which formed relatively short oligomers did not interact with GyrA. The size of nucleoid in PprA mutant (1.9564 +/- 0.324 um) was significantly bigger than the wild type (1.6437 +/- 0.345 um). Thus, we showed that DrGyr confers all three activities of bacterial type IIA family DNA topoisomerases, which are differentially regulated by PprA, highlighting the significant role of PprA in DrGyr activity regulation and genome maintenance in D. radiodurans. PMID- 26847199 TI - Large-scale biofilm cultivation of Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 for physiologic studies and drug discovery. AB - Microbial biofilms are mainly studied due to detrimental effects on human health but they are also well established in industrial biotechnology for the production of chemicals. Moreover, biofilm can be considered as a source of novel drugs since the conditions prevailing within biofilm can allow the production of specific metabolites. Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 when grown in biofilm condition produces an anti-biofilm molecule able to inhibit the biofilm of the opportunistic pathogen Staphylococcus epidermidis. In this paper we set up a P. haloplanktis TAC125 biofilm cultivation methodology in automatic bioreactor. The biofilm cultivation was designated to obtain two goals: (1) the scale up of cell-free supernatant production in an amount necessary for the anti-biofilm molecule/s purification; (2) the recovery of P. haloplanktis TAC125 cells grown in biofilm for physiological studies. We set up a fluidized bed reactor fermentation in which floating polystyrene supports were homogeneously mixed, exposing an optimal air-liquid interface to let bacterium biofilm formation. The proposed methodology allowed a large-scale production of anti-biofilm molecule and paved the way to study differences between P. haloplanktis TAC125 cells grown in biofilm and in planktonic conditions. In particular, the modifications occurring in the lipopolysaccharide of cells grown in biofilm were investigated. PMID- 26847201 TI - Pressure adaptation of 3-isopropylmalate dehydrogenase from an extremely piezophilic bacterium is attributed to a single amino acid substitution. AB - 3-Isopropylmalate dehydrogenase (IPMDH) from the extreme piezophile Shewanella benthica (SbIPMDH) is more pressure-tolerant than that from the atmospheric pressure-adapted Shewanella oneidensis (SoIPMDH). To understand the molecular mechanisms of this pressure tolerance, we analyzed mutated enzymes. The results indicate that only a single mutation at position 266, corresponding to Ala (SbIPMDH) and Ser (SoIPMDH), essentially affects activity under higher-pressure conditions. Structural analyses of SoIPMDH suggests that penetration of three water molecules into the cleft around Ser266 under high-pressure conditions could reduce the activity of the wild-type enzyme; however, no water molecule is observed in the Ala266 mutant. PMID- 26847202 TI - Radiologists' Usage of Social Media: Results of the RANSOM Survey. AB - The growing use of social media is transforming the way health care professionals (HCPs) are communicating. In this changing environment, it could be useful to outline the usage of social media by radiologists in all its facets and on an international level. The main objective of the RANSOM survey was to investigate how radiologists are using social media and what is their attitude towards them. The second goal was to discern differences in tendencies among American and European radiologists. An international survey was launched on SurveyMonkey ( https://www.surveymonkey.com ) asking questions about the platforms they prefer, about the advantages, disadvantages, and risks, and about the main incentives and barriers to use social media. A total of 477 radiologists participated in the survey, of which 277 from Europe and 127 from North America. The results show that 85 % of all survey participants are using social media, mostly for a mixture of private and professional reasons. Facebook is the most popular platform for general purposes, whereas LinkedIn and Twitter are more popular for professional usage. The most important reason for not using social media is an unwillingness to mix private and professional matters. Eighty-two percent of all participants are aware of the educational opportunities offered by social media. The survey results underline the need to increase radiologists' skills in using social media efficiently and safely. There is also a need to create clear guidelines regarding the online and social media presence of radiologists to maximize the potential benefits of engaging with social media. PMID- 26847204 TI - Cumulative social risk exposure in childhood and smoking and excessive alcohol use in adulthood. AB - BACKGROUND: Social inequalities in adult smoking and excessive alcohol intake may be associated with exposure to multiple childhood social risk factors across different domains of risk within the household. METHODS: We used data from a cross-sectional cohort study of adults (40-75 years) in 1993-97 living in England (N = 19466) to examine the association between clusters of childhood social risks across different domains with adult smoking and excessive alcohol use. Participants reported exposure to six childhood social risk factors, current smoking behaviour and alcohol intake. Factor analysis was used to identify domains of social risk. We created a childhood cumulative domain social risk score (range 0-2) from summing the total number of domains. RESULTS: Factor analysis identified two domains of childhood social risk within the household: maladaptive family functioning (parental unemployment, substance misuse, physical abuse) and parental separation experiences : maternal separation, divorce, being sent away from home). Compared to those children with risk exposure in no single domain, children with risk exposure in both domains (i.e. maladaptive family functioning, parental separation experiences) had a higher prevalence of adult smoking [men: Prevalence ratio (PR) = 1.74, 95% confidence intervals (CI): 1.35 2.26; women: PR = 1.71 95% CI: 1.34-2.18]. There was a trend association between the number of childhood social risk domains and adult smoking (both sexes: P < 0.001) and excessive alcohol use (men: P <0.008). CONCLUSIONS: Further work is needed to understand if addressing cumulative risk exposure to maladaptive family functioning and parental separation experiences can reduce social inequalities in adult smoking and excessive alcohol intake. PMID- 26847203 TI - A Comparison of Lung Nodule Segmentation Algorithms: Methods and Results from a Multi-institutional Study. AB - Tumor volume estimation, as well as accurate and reproducible borders segmentation in medical images, are important in the diagnosis, staging, and assessment of response to cancer therapy. The goal of this study was to demonstrate the feasibility of a multi-institutional effort to assess the repeatability and reproducibility of nodule borders and volume estimate bias of computerized segmentation algorithms in CT images of lung cancer, and to provide results from such a study. The dataset used for this evaluation consisted of 52 tumors in 41 CT volumes (40 patient datasets and 1 dataset containing scans of 12 phantom nodules of known volume) from five collections available in The Cancer Imaging Archive. Three academic institutions developing lung nodule segmentation algorithms submitted results for three repeat runs for each of the nodules. We compared the performance of lung nodule segmentation algorithms by assessing several measurements of spatial overlap and volume measurement. Nodule sizes varied from 29 MUl to 66 ml and demonstrated a diversity of shapes. Agreement in spatial overlap of segmentations was significantly higher for multiple runs of the same algorithm than between segmentations generated by different algorithms (p < 0.05) and was significantly higher on the phantom dataset compared to the other datasets (p < 0.05). Algorithms differed significantly in the bias of the measured volumes of the phantom nodules (p < 0.05) underscoring the need for assessing performance on clinical data in addition to phantoms. Algorithms that most accurately estimated nodule volumes were not the most repeatable, emphasizing the need to evaluate both their accuracy and precision. There were considerable differences between algorithms, especially in a subset of heterogeneous nodules, underscoring the recommendation that the same software be used at all time points in longitudinal studies. PMID- 26847205 TI - Dietary leucine supplementation minimises tumour-induced damage in placental tissues of pregnant, tumour-bearing rats. AB - BACKGROUND: The occurrence of cancer during pregnancy merges two complex, poorly understood metabolic and hormonal conditions. This association can exacerbate the conditions of both the mother and the foetus. The branched-chain amino acid leucine enhances cellular activity, particularly by increasing protein synthesis. This study aimed to analyse the modulatory effect of a leucine-rich diet on direct and indirect tumour-induced placental damage. This was accomplished by evaluating the expression of genes involved in protein synthesis and degradation and assessing anti-oxidant enzyme activity in placental tissues collected from pregnant, tumour-bearing rats. RESULTS: Pregnant rats were either implanted with Walker 256 tumour cells or injected with ascitic fluid (to study the indirect effects of tumour growth) and then fed a leucine-rich diet. Animals in a control group underwent the same procedures but were fed a normal diet. On the 20(th) day of pregnancy, tumour growth was observed. Dams fed a normoprotein diet showed the greatest tumour growth. Injection with ascitic fluid mimicked the effects of tumour growth. Decreased placental protein synthesis and increased protein degradation were observed in both the tumour-bearing and the ascitic fluid injected groups that were fed a normoprotein diet. These effects resulted in low placental DNA and protein content and high lipid peroxidation (measured by malondialdehyde content). Decreased placental protein synthesis-related gene expression was observed in the tumour group concomitant with increased expression of genes encoding protein degradation-associated proteins and proteolytic subunits. CONCLUSIONS: Consumption of a leucine-rich diet counteracted the effects produced by tumour growth and injection with ascitic fluid. The diet enhanced cell signalling, ameliorated deficiencies in DNA and protein content, and balanced protein synthesis and degradation processes in the placenta. The improvements in cell signalling included changes in the mTOR/eIF pathway. In conclusion, consumption of a leucine-rich diet improved placental metabolism and cell signalling in tumour-bearing rats, and these changes reduced the deleterious effects caused by tumour growth. PMID- 26847206 TI - Application of mosquito repellent coils and associated self-reported health issues in Ghana. AB - BACKGROUND: The use of mosquito coils has gained widespread patronage in malaria endemic countries, even though it is not a recommended preventive measure for avoiding mosquitoes. Mosquito coils contain insecticides, which are expected to vaporize slowly once the coil is lit, to provide protection against the mosquito. The mosquito coil base material contains a variety of compounds capable of burning slowly to gradually release the insecticide. The mosquito coil smoke, however, is potentially a source of indoor air pollution with implications for acute respiratory infections (ARI) and other illnesses. The present study investigated the application of mosquito coils and associated self-reported health issues in Ghana. METHODS: A cross-sectional study was undertaken in which questionnaires were randomly administered to 480 households across four districts in Ghana. Respondents who exclusively applied mosquito coils were grouped as test cohort, while those who did not apply any mosquito repellency method constituted a control cohort. RESULTS: The test group that applied mosquito coils reported malaria incidence rate of 86.3 %. The control group that did not apply any mosquito repellency method reported an incidence rate of malaria at 72.4 %. Chi square analysis suggested that the observed difference was statistically significant (x (2) = 4.25; p = 0.04). The number of respondents who reported symptoms of cough from mosquito coil application (52.6 % incidence rate) was marginally greater than their counterparts who did not apply coils (46.1 % incidence rate). It was also found that respondents with shortage of breath, which was used as a proxy for ARI, were more likely to have applied mosquito coil. CONCLUSIONS: The application of mosquito coils did not necessarily reduce the incidence of malaria in the study communities. It however presented a potential respiratory risk factor, which should be further investigated by critically examining exposure to particulate matter emissions from burning coils. PMID- 26847210 TI - Overexpression of SCARA5 inhibits tumor proliferation and invasion in osteosarcoma via suppression of the FAK signaling pathway. AB - Scavenger receptor class A, member 5 (SCARA5) is a member of the scavenger receptor family, and is involved in several types of human malignancy; however, its roles in osteosarcoma (OS) remain to be fully elucidated. Therefore, in the present study, the biological functions of SCARA5 in OS, and the potential underlying mechanisms were investigated. SCARA5 expression in OS tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction and western blot analysis. The effects of SCARA5 on the proliferation and migration/invasion ability of OS cells were determined by MTT and Transwell chamber assays, respectively. Expression levels of phosphorylated focal adhesion kinase (p-FAK), FAK, p-Src, Src, matrix metalloproteinase (MMP)2 and MMP9 were evaluated via western blot analysis. The results of the present study demonstrated that SCARA5 was expressed at low levels in OS tissues and cell lines. The overexpression of SCARA5 significantly inhibited the proliferation, colony formation and migration/invasion abilities of the OS cells. Furthermore, SCARA5 significantly decreased the expression levels of p-FAK, MMP-2 and MMP-9 in the OS cells. Taken together, these data suggested that the overexpression of SCARA5 inhibits tumor proliferation and invasion in OS via suppression of the FAK signaling pathway. Thus, novel therapeutic strategies or drugs targeted at SCARA5 may offer potential for the treatment of OS. PMID- 26847207 TI - Emergence of two prion subtypes in ovine PrP transgenic mice infected with human MM2-cortical Creutzfeldt-Jakob disease prions. AB - INTRODUCTION: Mammalian prions are proteinaceous pathogens responsible for a broad range of fatal neurodegenerative diseases in humans and animals. These diseases can occur spontaneously, such as Creutzfeldt-Jakob disease (CJD) in humans, or be acquired or inherited. Prions are primarily formed of macromolecular assemblies of the disease-associated prion protein PrP(Sc), a misfolded isoform of the host-encoded prion protein PrP(C). Within defined host species, prions can exist as conformational variants or strains. Based on both the M/V polymorphism at codon 129 of PrP and the electrophoretic signature of PrP(Sc) in the brain, sporadic CJD is classified in different subtypes, which may encode different strains. A transmission barrier, the mechanism of which remains unknown, limits prion cross-species propagation. To adapt to the new host, prions have the capacity to 'mutate' conformationally, leading to the emergence of a variant with new biological properties. Here, we transmitted experimentally one rare subtype of human CJD, designated cortical MM2 (129 MM with type 2 PrP(Sc)), to transgenic mice overexpressing either human or the VRQ allele of ovine PrP(C). RESULTS: In marked contrast with the reported absence of transmission to knock-in mice expressing physiological levels of human PrP, this subtype transmitted faithfully to mice overexpressing human PrP, and exhibited unique strain features. Onto the ovine PrP sequence, the cortical MM2 subtype abruptly evolved on second passage, thereby allowing emergence of a pair of strain variants with distinct PrP(Sc) biochemical characteristics and differing tropism for the central and lymphoid tissues. These two strain components exhibited remarkably distinct replicative properties in cell-free amplification assay, allowing the 'physical' cloning of the minor, lymphotropic component, and subsequent isolation in ovine PrP mice and RK13 cells. CONCLUSIONS: Here, we provide in-depth assessment of the transmissibility and evolution of one rare subtype of sporadic CJD upon homologous and heterologous transmission. The notion that the environment or matrix where replication is occurring is key to the selection and preferential amplification of prion substrain components raises new questions on the determinants of prion replication within and between species. These data also further interrogate on the interplay between animal and human prions. PMID- 26847209 TI - Haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence. AB - BACKGROUND: Spindle assembly checkpoint components BubR1 and Sgo1 play a key role in the maintenance of chromosomal instability during cell division. These proteins function to block the anaphase entry until all condensed chromosomes have been attached by the microtubules emanating from both spindle poles. Haplo insufficiency of either BubR1 or SGO1 results in enhanced chromosomal instability and tumor development in the intestine. Recent studies show that spindle checkpoint proteins also have a role in slowing down the ageing process. Therefore, we want to study whether haplo-insufficiency of both BubR1 and SGO1 accelerates cellular senescence in mice. METHODS: We took advantage of the availability of BubR1 and SGO1 knockout mice and generated primary murine embryonic fibroblasts (MEFs) with mutations in either BubR1, SGO1, or both and analyzed cellular senescence of the MEFs of various genetic backgrounds. RESULTS: We observed that BubR1(+/-) SGO(+/-) MEFs had an accelerated cellular senescence characterized by morphological changes and expressed senescence-associated beta galactosidase. In addition, compared with wild-type MEFs or MEFs with a single gene deficiency, BubR1(+/-) SGO1(+/-) MEFs expressed enhanced levels of p21 but not p16. CONCLUSIONS: Taken together, our observations suggest that combined deficiency of BubR1 and Sgo1 accelerates cellular senescence. PMID- 26847211 TI - More on Women's Health, Gender Medicine, and the Complexities of Personalized Medicine. PMID- 26847212 TI - Levulinic Acid Biorefineries: New Challenges for Efficient Utilization of Biomass. AB - Levulinic acid is a sustainable platform molecule that can be upgraded to valuable chemicals and fuel additives. This article focuses on the catalytic upgrading of levulinic acid into various chemicals such as levulinate esters, delta-aminolevulinic acid, succinic acid, diphenolic acid, gamma-valerolactone, and gamma-valerolactone derivatives such valeric esters, 5-nonanone, alpha methylene-gamma valerolactone, and other various molecular-weight alkanes (C9 and C18-C27 olefins). PMID- 26847213 TI - Comparison of choroidal thickness changes following intravitreal dexamethasone, ranibizumab, and triamcinolone in eyes with retinal vein occlusion. AB - PURPOSE: To evaluate short-term choroidal thickness changes following intravitreal dexamethasone implant (DEX), ranibizumab (RAN), and triamcinolone acetonide (TA) in eyes with retinal vein occlusion (RVO) and macular edema (ME). METHODS: In this prospective study, 35 eyes of 35 patients with RVO and ME who were treated with intravitreal injections of DEX, RAN, and TA were included. Choroidal thickness was measured using semiautomated segmentation of enhanced depth imaging with optical coherence tomography at fovea and parafoveal areas. Changes in choroidal thickness following treatment were compared statistically. RESULTS: Choroidal thickness decreased following DEX, RAN, and TA treatments (all p>0.05). In the DEX group, at the first month nasal 1,500 um (N11,500) and at the third month subfoveal (SF3) and nasal 500 um (N3500) choroidal thickness revealed a significant reduction compared to RAN and TA groups (all p<0.05). In the TA group, choroidal thickness showed a significant reduction only at nasal 1,500 um (N31,500) at the third month (p<0.05). CONCLUSIONS: Choroidal thickness was decreased in all 3 groups. The DEX and TA groups showed a significant reduction at some areas. Ranibizumab had the smallest effect on choroidal thickness after 3 months among all groups. PMID- 26847214 TI - Plastic Biliary Stent Migration During Multiple Stents Placement and Successful Endoscopic Removal Using Intra-Stent Balloon Inflation Technique: A Case Report and Literature Review. AB - BACKGROUND: Late migration of a plastic biliary stent after endoscopic placement is a well known complication, but there is little information regarding migration of a plastic stent during multiple stents placement. CASE REPORT: A white man was hospitalized for severe jaundice due to neoplastic hilar stenosis. Surgical eligibility appeared unclear on admission and endoscopy was carried out, but the first stent migrated proximally at the time of second stent insertion. After failed attempts with various devices, the migrated stent was removed successfully through cannulation with a dilation balloon. CONCLUSIONS: The migration of a plastic biliary stent during multiple stents placement is a possible complication. In this context, extraction can be very complicated. In our patient, cannulation of a stent with a dilation balloon was the only effective method. PMID- 26847215 TI - Validity of questionnaire-based assessment of sedentary behaviour and physical activity in a population-based cohort of older men; comparisons with objectively measured physical activity data. AB - BACKGROUND: Older adults are the most inactive age group and self-reporting of activities may be complicated by age-related reductions in structured activities and misclassification or recall biases. We investigate the validity of simple questionnaires about sedentary behaviour (SB), (including the widely used proxy television (TV) viewing), and physical activity (PA) in comparison with objective measures. METHODS: Community dwelling men aged 71-93 years, from a UK population based cohort wore a GT3X accelerometer over the right hip for 7 days and self completed a questionnaire including information about SB (TV, reading, computer use and car use) and PA (leisure and sporting domains). RESULTS: 1566/3137 surviving men (mean age 79 years) attended. 1377 ambulatory men provided questionnaire and accelerometer data. Questionnaires under-estimated mean daily sedentary time; 317 minutes total SB (TV, computer use, reading or driving), 176 minutes (TV) vs 619 minutes (objectively measured). Correlations between objective measures and self-reports were 0.18 (total SB) and 0.17 (TV), both P < 0.001. Objective SB levels were similar across the lowest three quartiles of self reported SB but raised in the highest quartile. Correlations between steps/day or moderate to vigorous PA with self-reported total PA were both 0.49, P < 0.001 and measured PA levels were progressively higher at higher levels of self-reported PA. CONCLUSIONS: Among older men, simple SB questions performed poorly for identifying total SB time, although simple PA questions were associated with a graded increase with objectively measured PA. Future studies of health effects of SB in older men would benefit from objective measures of SB. PMID- 26847217 TI - Prognostic Value of Serial Changes in High-Sensitivity Cardiac Troponin I and T over 3 Months Using Reference Change Values in Hemodialysis Patients. AB - INTRODUCTION: Serial changes in cardiac troponin in hemodialysis (HD) patients have uncertain clinical implications. We evaluated associations of adverse outcomes in HD patients with reference change value (RCV) data and tertile concentrations for cardiac troponin I (cTnI) and cTnT measured by high sensitivity (hs) assays. METHODS: RCV data and tertiles for hs-cTnI and hs-cTnT were determined from plasma samples collected 3 months apart in 677 stable outpatient HD patients and assessed for their associations with adverse outcomes using adjusted Cox models. Primary outcomes were all-cause mortality and sudden cardiac death (SCD). RESULTS: During a median follow-up of 23 months, 18.6% of patients died. RCVs were: hs-cTnI +37% and -30%; hs-cTnT +25% and -20%. Patients with serial hs-cTnI and hs-cTnT changes >RCV (increase or decrease) had all-cause mortality of 25.2% and 23.8% respectively, compared to 15.0% and 16.5% with changes <=RCV [adjusted hazard ratios (aHRs): 1.9, P = 0.0003 and 1.7, P = 0.0066), respectively]. Only hs-cTnI changes >RCV were predictive of SCD (aHR 2.6, P = 0.005). hs-Cardiac troponin changes >RCV improved all-cause mortality prognostication compared to changes <=RCV in tertile 2: hs-cTnI aHR, 2.70 (P = 0.003); hs-cTnT aHR, 1.98 (P = 0.043). The aHR of changes in hs-cTnI in tertile 2 >RCV for SCD was 5.62 (P = 0.039). CONCLUSIONS: Changes over 3 months in hs-cTnI and hs-cTnT of >RCV identified patients at greater risk of all-cause mortality, and for hs-cTnI were also predictive of SCD. Among patients with middle tertile cardiac troponin concentrations, hs-cTnI changes >RCV provided additive prognostic value for both SCD and all-cause mortality, whereas those for hs-cTnT provided additive prognostic value only for all-cause mortality. PMID- 26847218 TI - Systematic Evaluation of Sanger Validation of Next-Generation Sequencing Variants. AB - BACKGROUND: Next-generation sequencing (NGS) data are used for both clinical care and clinical research. DNA sequence variants identified using NGS are often returned to patients/participants as part of clinical or research protocols. The current standard of care is to validate NGS variants using Sanger sequencing, which is costly and time-consuming. METHODS: We performed a large-scale, systematic evaluation of Sanger-based validation of NGS variants using data from the ClinSeq(r) project. We first used NGS data from 19 genes in 5 participants, comparing them to high-throughput Sanger sequencing results on the same samples, and found no discrepancies among 234 NGS variants. We then compared NGS variants in 5 genes from 684 participants against data from Sanger sequencing. RESULTS: Of over 5800 NGS-derived variants, 19 were not validated by Sanger data. Using newly designed sequencing primers, Sanger sequencing confirmed 17 of the NGS variants, and the remaining 2 variants had low quality scores from exome sequencing. Overall, we measured a validation rate of 99.965% for NGS variants using Sanger sequencing, which was higher than many existing medical tests that do not necessitate orthogonal validation. CONCLUSIONS: A single round of Sanger sequencing is more likely to incorrectly refute a true-positive variant from NGS than to correctly identify a false-positive variant from NGS. Validation of NGS derived variants using Sanger sequencing has limited utility, and best practice standards should not include routine orthogonal Sanger validation of NGS variants. PMID- 26847216 TI - Infertility and Perinatal Loss: When the Bough Breaks. AB - Infertility and perinatal loss are common, and associated with lower quality of life, marital discord, complicated grief, major depressive disorder, anxiety disorders, and post-traumatic stress disorder. Young women, who lack social supports, have experienced recurrent pregnancy loss or a history of trauma and / or preexisting psychiatric illness are at a higher risk of experiencing psychiatric illnesses or symptoms after a perinatal loss or during infertility. It is especially important to detect, assess, and treat depression, anxiety, or other psychiatric symptoms because infertility or perinatal loss may be caused or perpetuated by such symptoms. Screening, psychoeducation, provision of resources and referrals, and an opportunity to discuss their loss and plan for future pregnancies can facilitate addressing mental health concerns that arise. Women at risk of or who are currently experiencing psychiatric symptoms should receive a comprehensive treatment plan that includes the following: (1) proactive clinical monitoring, (2) evidence-based approaches to psychotherapy, and (3) discussion of risks, benefits, and alternatives of medication treatment during preconception and pregnancy. PMID- 26847219 TI - [A role for hypnosis in cataract surgery: Report of 171 procedures]. AB - OBJECTIVES: To study the effectiveness of relaxation hypnosis in outpatient cataract surgery. STUDY DESIGN: Prospective study of 171 patients undergoing cataract surgery under hypnosis, performed by the same nurse anesthetist. The procedures were performed by 2 senior surgeons, A and B (A=78 surgeries, and B=93 surgeries) under topical anesthesia and with a 2.2-mm mini-incision. The hypnosis group (n=102) was compared to a control group (n=69) according to quantitative, objective criteria: hemodynamic changes and the need for intravenous medication in operating room, as well as subjective, qualitative criteria: surgical comfort, effectiveness of hypnosis, and patient satisfaction. Subgroup analyses by surgeon, 1st and 2nd eye surgery, were performed. RESULTS: Hemodynamic parameters were not significantly different between the 2 groups: systolic blood pressure (P=0.06) and maximum heart rate (P=0.25). However, the use of intraoperative intravenous medication was significantly higher in the control group (49.3% versus 21.6%, P<0.001). The effectiveness of relaxation was scored at a mean of 5.25/6 by the nurse anesthetist. The patients in the hypnosis group reported a mean comfort rating of 8.4/10, and 100% were satisfied with this hypnosis experience. CONCLUSIONS: Preliminary results of this study are very positive for all three parties: patient/anesthetist/surgeon. They are leading to an expanded university training program for operating room personnel in order to improve quality of care and reduce premedication in elderly patients so as to facilitate their return to home. PMID- 26847220 TI - [Lacrimal traumatology]. AB - Lacrimal system injuries represent a significant part of ocular emergencies and mainly affect males of various ages including very young children. The most frequent presentations are canalicular laceration with a palpebral wound medial to the lacrimal punctum. The inferior canaliculus is the most commonly affected but bilateral injuries or injuries affecting both canaliculi can occur. The main causes are dog bites in children, scuffles in young adults and falls in elderlies. Antitetanic and antirabic measures have to be considered for open cases. The diagnosis is easily made by inspection and can be confirmed by probing. Other lesions can be associated and require proper identification, especially eyeball laceration requiring surgical repair within 6 hours. Otherwise, isolated canalicular wounds are to be repaired within 48 hours by an anastomotic suture with or without mono- or bi-canalicular silicone intubation. Other lacrimal tract injuries involving the lacrimal sac or the nasolacrimal duct are rare, commonly associated with blunt craniofacial trauma or iatrogenic after some surgical procedures. PMID- 26847221 TI - [Pathomimia in ophthalmology: We must acknowledge it!]. AB - Pathomimia is an unconscious falsification of physical manifestations. The eyelids and ocular surface are almost always affected because of the easy accessibility to these structures for the purpose of attracting attention from one's entourage as well as the medical community. We report four cases of lid and conjunctival pathomimia. The diagnosis was made after a long follow-up and numerous ancillary tests. PMID- 26847223 TI - Paediatric HIV: the law of amplified returns. PMID- 26847222 TI - Purification, biochemical characterization and structural modelling of alkali stable beta-1,4-xylan xylanohydrolase from Aspergillus fumigatus R1 isolated from soil. AB - BACKGROUND: Aspergillus fumigatus R1 produced xylanase under submerged fermentation which degrades the complex hemicelluloses contained in agricultural substrates. Xylanases have gained considerable attention because of their tremendous applications in industries. The purpose of our study was to purify xylanase and study its biochemical properties. We have predicted the secondary structure of purified xylanase and evaluated its active site residues and substrate binding sites based on the global and local structural similarity. RESULTS: Various microorganisms were isolated from Puducherry soil and screened by Congo-red test. The best isolate was identified to be Aspergillus fumigatus R1. The production kinetics showed the highest xylanase production (208 IU/ml) by this organism in 96 h using 1 % rice bran as the only carbon source. The purification of extracellular xylanase was carried out by fractional ammonium sulphate precipitation (30-55 %), followed by extensive dialysis and Bio-Gel P-60 Gel-filtration chromatography. The enzyme was purified 58.10 folds with a specific activity of 38196.22 IU/mg. The biochemical characterization of the pure enzyme was carried out for its optimum pH and temperature (5.0 and 50(0)C), pH and temperature stability, molecular mass (Mr) (24.5 kDa) and pI (6.29). The complete sequence of protein was obtained by mass spectrometry analysis. Apparent Km and Vmax values of the xylanase for birchwood xylan were 11.66 mg/ml and 87.6 MUmol min(-1) mg(-1) respectively. CONCLUSION: Purified xylanase was analyzed by mass-spectrometry which revealed 2 unique peptides. Xylanase under current study showed significant production using agricultural residues and a broad range of pH stability in the alkaline region. Xylanase produced by Aspergillus fumigatus R1 could serve as the enzyme of choice in industries. PMID- 26847224 TI - Can abacavir be used safely in children without HLA testing? PMID- 26847225 TI - Enhancement of clinical decision making in HIV care in Africa. PMID- 26847226 TI - Can cash help eliminate mother-to-child HIV transmission? PMID- 26847227 TI - HIV transmission in MSM: considerations for PrEP scale-up. PMID- 26847228 TI - Adverse events associated with abacavir use in HIV-infected children and adolescents: a systematic review and meta-analysis. AB - BACKGROUND: Concerns exist about the toxicity of drugs used in the implementation of large-scale antiretroviral programmes, and documentation of antiretroviral toxicity is essential. We did a systematic review and meta-analysis of adverse events among children and adolescents receiving regimens that contain abacavir, a widely used antiretroviral drug. METHODS: We searched bibliographic databases and abstracts from relevant conferences from Jan 1, 2000, to March 1, 2015. All experimental and observational studies of HIV-infected patients aged 0-18 years who used abacavir, were eligible. Incidence of adverse outcomes in patients taking abacavir (number of new events in a period divided by population at risk at the beginning of the study) and relative risks (RR) compared with non-abacavir regimens were pooled with random effects models. FINDINGS: Of 337 records and 21 conference abstracts identified, nine studies (eight full-text articles and one abstract) collected information about 2546 children, of whom 1769 (69%) were on abacavir regimens. Among children and adolescents taking abacavir, hypersensitivity reactions (eight studies) had a pooled incidence of 2.2% (95% CI 0.4-5.2); treatment switching or discontinuation (seven studies) pooled incidence was 10.9% (2.1-24.3); of grade 3-4 adverse events (six studies) pooled incidence was 9.9% (2.4-20.9); and adverse events other than hypersensitivity reaction (six studies) pooled incidence was 21.5% (2.8-48.4). Between-study inconsistency was significant for all outcomes (p<0.0001 for all inconsistencies). Incidence of death (four studies) was 3.3% (95% CI 1.5-5.6). In the three randomised clinical trials with comparative data, no increased risk of hypersensitivity reaction (pooled RR 1.08; 95% CI 0.19-6.15), grade 3 or 4 events (0.79 [0.44-1.42]), or death (1.72 [0.77-3.82]) was noted for abacavir relative to non-abacavir regimens. None of the reported deaths were related to abacavir. INTERPRETATION: Abacavir-related toxicity occurs early after ART initiation and is manageable. Abacavir can be safely used for first-line or second-line antiretroviral regimens in children and adolescents, especially in sub-Saharan Africa were HLA B5701 genotype is rare. FUNDING: WHO. PMID- 26847229 TI - Effect of a clinical decision support system on early action on immunological treatment failure in patients with HIV in Kenya: a cluster randomised controlled trial. AB - BACKGROUND: A clinical decision support system (CDSS) is a computer program that applies a set of rules to data stored in electronic health records to offer actionable recommendations. We aimed to establish whether a CDSS that supports detection of immunological treatment failure among patients with HIV taking antiretroviral therapy (ART) would improve appropriate and timely action. METHODS: We did this prospective, cluster randomised controlled trial in adults and children (aged >=18 months) who were eligible for, and receiving, ART at HIV clinics in Siaya County, western Kenya. Health facilities were randomly assigned (1:1), via block randomisation (block size of two) with a computer-generated random number sequence, to use electronic health records either alone (control) or with CDSS (intervention). Facilities were matched by type and by number of patients enrolled in HIV care. The primary outcome measure was the difference between groups in the proportion of patients who experienced immunological treatment failure and had a documented clinical action. We used generalised linear mixed models with random effects to analyse clustered data. This trial is registered with ClinicalTrials.gov, number NCT01634802. FINDINGS: Between Sept 1, 2012, and Jan 31, 2014, 13 clinics, comprising 41,062 patients, were randomly assigned to the control group (n=6) or the intervention group (n=7). Data collection at each site took 12 months. Among patients eligible for ART, 10,358 (99%) of 10,478 patients were receiving ART at control sites and 10,991 (99%) of 11,028 patients were receiving ART at intervention sites. Of these patients, 1125 (11%) in the control group and 1342 (12%) in the intervention group had immunological treatment failure, of whom 332 (30%) and 727 (54%), respectively, received appropriate action. The likelihood of clinicians taking appropriate action on treatment failure was higher with CDSS alerts than with no decision support system (adjusted odds ratio 3.18, 95% CI 1.02-9.87). INTERPRETATION: CDSS significantly improved the likelihood of appropriate and timely action on immunological treatment failure. We expect our findings will be generalisable to virological monitoring of patients with HIV receiving ART once countries implement the 2015 WHO recommendation to scale up viral load monitoring. FUNDING: US President's Emergency Plan for AIDS Relief (PEPFAR), through the US Centers for Disease Control and Prevention. PMID- 26847230 TI - Conditional cash transfers and uptake of and retention in prevention of mother-to child HIV transmission care: a randomised controlled trial. AB - BACKGROUND: Novel strategies are needed to increase retention in and uptake of prevention of mother-to-child HIV transmission (PMTCT) services in sub-Saharan Africa. We aimed to determine whether small, increasing cash payments, which were conditional on attendance at scheduled clinic visits and receipt of proposed services can increase the proportions of HIV-infected pregnant women who accept available PMTCT services and remain in care. METHODS: In this randomised controlled trial, we recruited newly diagnosed HIV-infected women, who were 32 or less weeks pregnant, from 89 antenatal care clinics in Kinshasa, Democratic Republic of Congo, and randomly assigned (1:1) them to either the intervention group or the control group using computer-based randomisation with varying block sizes of four, six, and eight. The intervention group received compensation on the condition that they attended scheduled clinic visits and accepted offered PMTCT services (US$5, plus US$1 increment at every subsequent visit), whereas the control group received usual care. Outcomes assessed included retention in care at 6 weeks' post partum and uptake of PMTCT services, measured by attendance of all scheduled clinic visits and acceptance of proposed services up to 6 weeks' post partum. Analyses were by intention to treat. This trial is registered with ClinicalTrials.org, number NCT01838005. FINDINGS: Between April 18, 2013, and Aug 30, 2014, 612 potential participants were identified, 545 were screened, and 433 were enrolled and randomly assigned; 217 to the control group and 216 to the intervention group. At 6 weeks' post partum, 174 participants in the intervention group (81%) and 157 in the control group (72%) were retained in care (risk ratio [RR] 1.11; 95% CI 1.00-1.24). 146 participants in the intervention group (68%) and 116 in the control group (54%) attended all clinic visits and accepted proposed services (RR 1.26; 95% CI 1.08-1.48). Results were similar after adjustment for marital status, age, and education. INTERPRETATION: Among women with newly diagnosed HIV, small, incremental cash incentives resulted in increased retention along the PMTCT cascade and uptake of available services. The cost-effectiveness of these incentives and their effect on HIV-free survival warrant further investigation. FUNDING: President's Emergency Plan for AIDS Relief and the National Institute of Health and Child Development. PMID- 26847231 TI - Effect of pre-exposure prophylaxis and combination HIV prevention for men who have sex with men in the UK: a mathematical modelling study. AB - BACKGROUND: HIV transmission in men who have sex with men (MSM) in the UK has shown no sign of decreasing in the past decade. Additional prevention measures are needed. We aimed to estimate the effect of various potential interventions implemented individually and in combination on prevention of HIV infection. METHODS: We extended a deterministic partnership-based mathematical model for HIV transmission, informed by detailed behavioural and surveillance data, to assess the effect of seven different HIV interventions implemented in MSM (aged 15-64 years) in the UK during 2014-20, including increasing rates of HIV testing, test and-treat programmes, pre-exposure prophylaxis (PrEP), and sexual behavioural changes. We did sensitivity analyses on risk compensation. FINDINGS: We predicted a baseline of 16 955 new infections (IQR 13 156-21 669) in MSM in the UK during 2014-20. At a coverage of <=50%, testing twice a year outperformed all other interventions. Of all intervention combinations, only the combined effect of test and treat and annual HIV testing (61.8%, IQR 47.2-81.8, of total incidence) was greater than the sum of effects of the two interventions individually (32.6%, 23.7-46.0, and 23.9%, 16.5-33.3, respectively). Simultaneous PrEP, expansion of HIV testing, and initiation of test-and-treat programme in 25% of high-activity MSM could save 7399 (IQR 5587-9813) UK MSM from HIV infection (43.6%, IQR 32.9 57.9, of total incidence). An increase in unsafe sex or sexual partners to 50% or more could substantially reduce the effect of interventions, but is unlikely to negate the prevention benefit completely. INTERPRETATION: PrEP could prevent a large number of new HIV infections if other key strategies including HIV testing and treatment are simultaneously expanded and improved. Without PrEP, HIV incidence in MSM in the UK is unlikely to decrease substantially by the end of this decade. FUNDING: Health Protection Agency (now Public Health England). PMID- 26847232 TI - SPARTA: Simple Program for Automated reference-based bacterial RNA-seq Transcriptome Analysis. AB - BACKGROUND: Many tools exist in the analysis of bacterial RNA sequencing (RNA seq) transcriptional profiling experiments to identify differentially expressed genes between experimental conditions. Generally, the workflow includes quality control of reads, mapping to a reference, counting transcript abundance, and statistical tests for differentially expressed genes. In spite of the numerous tools developed for each component of an RNA-seq analysis workflow, easy-to-use bacterially oriented workflow applications to combine multiple tools and automate the process are lacking. With many tools to choose from for each step, the task of identifying a specific tool, adapting the input/output options to the specific use-case, and integrating the tools into a coherent analysis pipeline is not a trivial endeavor, particularly for microbiologists with limited bioinformatics experience. RESULTS: To make bacterial RNA-seq data analysis more accessible, we developed a Simple Program for Automated reference-based bacterial RNA-seq Transcriptome Analysis (SPARTA). SPARTA is a reference-based bacterial RNA-seq analysis workflow application for single-end Illumina reads. SPARTA is turnkey software that simplifies the process of analyzing RNA-seq data sets, making bacterial RNA-seq analysis a routine process that can be undertaken on a personal computer or in the classroom. The easy-to-install, complete workflow processes whole transcriptome shotgun sequencing data files by trimming reads and removing adapters, mapping reads to a reference, counting gene features, calculating differential gene expression, and, importantly, checking for potential batch effects within the data set. SPARTA outputs quality analysis reports, gene feature counts and differential gene expression tables and scatterplots. CONCLUSIONS: SPARTA provides an easy-to-use bacterial RNA-seq transcriptional profiling workflow to identify differentially expressed genes between experimental conditions. This software will enable microbiologists with limited bioinformatics experience to analyze their data and integrate next generation sequencing (NGS) technologies into the classroom. The SPARTA software and tutorial are available at sparta.readthedocs.org. PMID- 26847233 TI - MicroRNA-let-7f-1 is induced by lycopene and inhibits cell proliferation and triggers apoptosis in prostate cancer. AB - Previous studies have suggested that lycopene has cytotoxic effects in a variety of types of human cancer. An improved understanding of the mechanisms underlying the anticancer effects of lycopene may provide novel therapeutic targets for cancer treatment. PC3 cells were treated with different concentrations of lycopene for 24 and 48 h, the level of protein kinase B (AKT2) was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Additionally, the expression levels of microRNA (miR)-let-7f-1 were measured using RT-qPCR. miR-let-7f-1 function was analyzed using cell proliferation and apoptosis assays in gain- and loss-of-function experiments. It was observed that lycopene downregulated the expression of AKT2 and upregulated the expression of miR-let-7f-1 in PC3 cells. Re-introduction of miR-let-7f-1 into PC3 cells was able to inhibit cell proliferation and induce apoptosis. Further investigation indicated that miR-let-7f-1 targeted AKT2 in PC3 cells and upregulation of AKT2 could attenuate the effects induced by miR-let-7f-1. The results of the current study indicate that miR-let-7f-1 is involved in the anticancer effects of lycopene and serves an important role in the inhibition of prostate cancer progression through the downregulation of AKT2. PMID- 26847234 TI - Stress and health Huangshan-style. AB - The Seventh International Congress of the Cell Stress Society International (CSSI) was held as a joint meeting with the newly organized committee of Stress Physiology, the Chinese Association for Physiological Sciences (CAPS). There were over 200 colleagues and their students in attendance from 22 different countries. The topics of the congress were core scientific areas in the field of stress and health. The keynote speakers were Fu-Chu He (China), E.R. (Ron) de Kloet (The Netherlands), and Kazuhiro Nagata (Japan). The CSSI Medallion for Career Achievement in the cell stress and chaperones field was awarded to Kazutoshi Mori (Japan). Twelve student post awards were given in recognition of a very high quality poster session. In the tradition of this series of congresses, cultural events were an important part of the program. In addition, participants became better acquainted during trips to the ancient shopping street, an evening at the Chinese opera, and a lesson in Tai Chi from a master. The first groups of CSSI Fellows and Senior Fellows were presented their rosettes and certificates during the congress. PMID- 26847235 TI - [The significance of biobanks for clinical development]. AB - Access to samples in biobanks and collection of samples for evaluation of biomarkers in clinical trials are an essential basis for the identification and development of biomarkers. From the perspective of a research-based pharmaceutical company identification of biomarkers and the accompanying diagnostics are an essential prerequisite for the further evolution of personalised healthcare-and the key to more effective and efficient healthcare. Research-based pharmaceutical companies can basically use four types of biobanks: biobanks of university hospitals, commercial providers, collaborative groups and company-owned biobanks. Areas of application, arising from the use of biobanks in the context of clinical development, are collection of prevalence data, evaluation of biomarker stability in different disease stages, technical validation of assays, an optimized course of clinical studies by focusing on defined, biomarker-stratified groups of patients and pharmacogenetic research. Challenges are, in particular, the availability of clinically annotated samples and tissue matching blood samples, in addition to sample quality, number and amount. An acceptable legal and regulatory framework, as well as the positive perception of biomarker data by politicians and the public, are important prerequisites for translational research for identification of biomarkers in clinical studies. Also, the early establishment of research alliances between academia and the pharmaceutical industry are required to transfer research results in new strategies for prevention, diagnosis and treatment of patients. PMID- 26847236 TI - Assessing within-woman changes in mammographic density: a comparison of fully versus semi-automated area-based approaches. AB - BACKGROUND: Mammographic density (MD) varies throughout a woman's life. We compared the performance of a fully automated (ImageJ-based) method to the observer-dependent Cumulus approach in the assessment of within-woman changes in MD over time. METHODS: MD was assessed in annual pre-diagnostic films (from age 40 to early 50s) from 313 breast cancer cases and 452 matched controls using Cumulus (left medio-lateral oblique (MLO) readings) and the ImageJ-based method (mean left-right MLO readings). Linear mixed models were used to compare within woman changes in MD among controls. Associations between individual-specific MD trajectories and breast cancer were examined using conditional logistic regression. RESULTS: The age-related trajectories predicted by Cumulus and the ImageJ-based method were similar for all MD measures, except that the ImageJ based method yielded slightly higher (by 2.54%, 95% CI 2.07%, 3.00%) estimates for percent MD. For both methods, the yearly rate of change in percent MD was twice faster after menopause than before, and higher BMI was associated with lower mean percent MD, but not associated with rate of change. Both methods yielded similar associations of individual-specific MD trajectories with breast cancer risk. CONCLUSIONS: The ImageJ-based method is a valid fully automated alternative to Cumulus for measuring within-woman changes in MD in digitized films. The Age Trial is registered as an International Standard Randomized Controlled Trial, number ISRCTN24647151. PMID- 26847242 TI - [Commentaire de la lettre a la redaction de Max Goyffon " La penurie de serums antivenimeux "]. PMID- 26847243 TI - Novel regulatory variant detected on the VKORC1 haplotype that is associated with warfarin dose. AB - AIM: Warfarin dose requirement is associated with VKORC1 rs9923231, and we studied whether it is a functional variant. MATERIALS & METHODS: We selected variants in linkage disequilibrium with rs9923231 that bind transcription factors in an allele-specific way. Representative haplotypes were cloned or constructed, nuclear protein binding and transcriptional activity were evaluated. RESULTS: rs56314408C>T and rs2032915C>T were detected in a liver enhancer in linkage disequilibrium with rs9923231. The rs56314408-rs2032915 C-C haplotype preferentially bound nuclear proteins and had higher transcriptional activity than T-T and the African-specific T-C. A motif for TFAP2A/C was disrupted by rs56314408T. No difference in transcriptional activity was detected for rs9923231G>A. CONCLUSION: Our results supported an activating role for rs56314408C, while rs9923231G>A had no evidence of being functional. PMID- 26847244 TI - A Triazole-Containing Metal-Organic Framework as a Highly Effective and Substrate Size-Dependent Catalyst for CO2 Conversion. AB - A highly porous metal-organic framework (MOF) incorporating both exposed metal sites and nitrogen-rich triazole groups was successfully constructed via solvothermal assembly of a clicked octcarboxylate ligand and Cu(II) ions, which presents a high affinity toward CO2 molecules clearly verified by gas adsorption and Raman spectral detection. The constructed MOF featuring CO2-adsorbing property and exposed Lewis-acid metal sites could serve as an excellent catalyst for CO2-based chemical fixation. Catalytic activity of the MOF was confirmed by remarkably high efficiency on CO2 cycloaddition with small epoxides. When extending the substrates to larger ones, its activity showed a sharp decrease. These observations reveal that MOF-catalyzed CO2 cycloaddition of small substrates was carried out within the framework, while large ones cannot easily enter into the porous framework for catalytic reactions. Thus, the synthesized MOF exhibits high catalytic selectivity to different substrates on account of the confinement of the pore diameter. The high efficiency and size-dependent selectivity toward small epoxides on catalytic CO2 cycloaddition make this MOF a promising heterogeneous catalyst for carbon fixation. PMID- 26847241 TI - Prevalence, risk factors and multilocus genotyping of Enterocytozoon bieneusi in farmed foxes (Vulpes lagopus), Northern China. AB - BACKGROUND: Microsporidiosis is a common disease in animals and humans around the world. Enterocytozoon bieneusi is the most common microsporidian species in humans. Many animal species may be a potential source of human microsporidiosis. However, information concerning prevalence and genotypes of E. bieneusi infection in farmed foxes (Vulpes lagopus) is scarce. Therefore, the present study examined prevalence, risk factors and genotypes of E. bieneusi in farmed foxes in northern China using a genetic approach. RESULTS: Of 302 fecal samples from farmed foxes, 37 (12.25%, 95% CI 8.55-15.95) were PCR-positive for E. bieneusi, and the prevalence was highly associated with the farming mode in that foxes raised outdoors (26.03% positive, 95% CI 18.91-33.15) had a significantly higher E. bieneusi prevalence than those raised indoors. Eleven internal transcribed spacer (ITS) genotypes were identified among the positive samples: four known E. bieneusi genotypes (Peru 8, Types IV, CHN-DC1 and D) and seven novel genotypes (NCF1-NCF7). Genotype NCF2 was the commonest (n = 13) and was found in five farms across three provinces (Jilin, Heilongjiang and Hebei). All genotypes belonged to phylogenetic group 1. Multilocus sequence typing (MLST) analyses revealed additional diversity. CONCLUSIONS: These findings indicate the presence of zoonotic E. bieneusi infection in farmed foxes in northern China. This is also the first report of genotypes Peru8, CHN-DC1 and Type IV, and seven novel genotypes (NCF1-NCF7) in farmed foxes by ITS combining with microsatellite and minisatellite markers for the first time. The results will provide baseline data for preventing and controlling E. bieneusi infection in farmed foxes, other animals and humans. PMID- 26847245 TI - Personalized medicine in thrombosis: back to the future. AB - Most physicians believe they practiced personalized medicine prior to the genomics era that followed the sequencing of the human genome. The focus of personalized medicine has been primarily genomic medicine, wherein it is hoped that the nucleotide dissimilarities among different individuals would provide clinicians with more precise understanding of physiology, more refined diagnoses, better disease risk assessment, earlier detection and monitoring, and tailored treatments to the individual patient. However, to date, the "genomic bench" has not worked itself to the clinical thrombosis bedside. In fact, traditional plasma based hemostasis-thrombosis laboratory testing, by assessing functional pathways of coagulation, may better help manage venous thrombotic disease than a single DNA variant with a small effect size. There are some new and exciting discoveries in the genetics of platelet reactivity pertaining to atherothrombotic disease. Despite a plethora of genetic/genomic data on platelet reactivity, there are relatively little actionable pharmacogenetic data with antiplatelet agents. Nevertheless, it is crucial for genome-wide DNA/RNA sequencing to continue in research settings for causal gene discovery, pharmacogenetic purposes, and gene gene and gene-environment interactions. The potential of genomics to advance medicine will require integration of personal data that are obtained in the patient history: environmental exposures, diet, social data, etc. Furthermore, without the ritual of obtaining this information, we will have depersonalized medicine, which lacks the precision needed for the research required to eventually incorporate genomics into routine, optimal, and value-added clinical care. PMID- 26847246 TI - Clinical impact of MYD88 mutations in chronic lymphocytic leukemia. PMID- 26847247 TI - Variability in the efficacy of the IL1 receptor antagonist anakinra for treating Erdheim-Chester disease. PMID- 26847248 TI - High dietary cholesterol intake during lactation promotes development of fatty liver in offspring of mice. AB - SCOPE: We have previously demonstrated in mice that a maternal high fat diet during lactation enhances the susceptibility of offspring to obesity and fatty liver. A causative molecule, however, is yet to be identified. Therefore, we examined the role of cholesterol, the dietary intake of which increases with consumption of a high fat diet. Excessive cholesterol intake is involved in the development of fatty liver, which in turn becomes a risk factor for metabolic syndrome, which includes obesity, insulin resistance, and dyslipidemia. However, our knowledge of the influences on offspring of excessive maternal cholesterol intake alone during pregnancy and lactation is limited. We examined how excessive maternal cholesterol intake during lactation influences susceptibility of the offspring to metabolic syndrome in mice. RESULTS: High cholesterol intake promoted triacylglycerol accumulation in the liver of offspring (p < 0.05), and elevated expression of molecules involved in hepatic lipoprotein influx was identified as the underlying mechanism. CONCLUSION: These findings demonstrate that excessive maternal cholesterol intake during lactation enhances the susceptibility of the offspring to development of fatty liver. PMID- 26847250 TI - Association of Fellowship Training With Otolaryngology Training Examination Scores. AB - IMPORTANCE: No prior studies have evaluated whether residents who pursue fellowship training achieve higher performance on the Otolaryngology Training Examination (OTE) and whether a specific fellowship will demonstrate a correlation with the corresponding specialty-specific OTE score. OBJECTIVES: To determine whether residents pursuing fellowship training achieve higher performance on the OTE and whether fellowship choice is correlated with higher scores on the related subspecialty section of the OTE. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis included 35 residents training in an academic otolaryngology residency program from July 1, 2003, to June 30, 2014. The OTE scores for postgraduate years 2 through 5 and the type of fellowship were collected for all residents meeting inclusion criteria. Data were collected from September 1 to October 15, 2014, and analyzed from October 16 to December 1, 2014. EXPOSURES: Residents were divided by whether they pursued fellowship training and by the type of fellowship chosen. MAIN OUTCOMES AND MEASURES: Outcome measures included comparison of scores between residents who pursued vs those who did not pursue fellowship training and comparison of subspecialty OTE scores between residents who pursued the corresponding fellowship and those who did not. RESULTS: Of the 35 residents who met the inclusion criteria (24 men and 11 women), 17 (49%) pursued fellowship training. The 3 most common fellowship choices were facial plastic and reconstructive surgery, pediatric otolaryngology, and rhinology (4 residents each [24%]). For all residents, mean scores on the OTE improved each subsequent training year, but this difference was only significant between postgraduate years 2 and 3 (from 60.9% to 68.6% correct; P < .001). Residents who pursued fellowship training did not perform better than those who did not (mean correct responses in postgraduate years 2-5, respectively, 59.6% vs 62.6% [P = .40]; 67.6% vs 71.2% [P = .33]; 71.2% vs 72.0% [P = .71]; and 71.4% vs 73.7% [P = .20]). Among residents who pursued the most common fellowships, no correlation was found between postgraduate year 5 scores on the related subspecialty section compared with the rest of the study group (mean correct responses for facial plastic and reconstructive surgery, 72.5% vs 74.7% [P = .67]; for pediatric otolaryngology, 72.9% vs 71.3% [P = .79]; and for rhinology, 72.2% vs 71.2% [P = .91]). CONCLUSIONS AND RELEVANCE: Residents who pursued fellowship training did not achieve higher scores on the OTE in any examination year compared with residents who did not pursue fellowship training and did not achieve higher scores within the OTE section that matched their chosen subspecialty in their last year of training. Fellowship choice does not appear to influence OTE scores among residents. PMID- 26847251 TI - Improving teaching skills: from interactive classroom to applicable knowledge. AB - Making the transition from more traditional to more interactive lecturing can be successfully achieved by applying numerous teaching techniques. To use lecture time in the most efficient way, a lecturer should first instruct students to acquire basic knowledge before coming to class. Various in-class activities then can be used to help students develop higher thinking skills and gain better understanding of the studied material. These in-class activities can take many forms (multiple-choice questions of various complexities, compare-and-contrast tasks, quantitative and problem-solving tasks, questions dealing with interpretations of tables, graphs, and charts, etc.) and should be designed to help student integrate their knowledge, to facilitate communication among students, and at the same time to allow the lecturer to closely monitor the learning process as it happens in the classroom. PMID- 26847252 TI - The XIIIth International Physiological Congress in Boston in 1929: American physiology comes of age. AB - In the 19th century, the concept of experimental physiology originated in France with Claude Bernard, evolved in Germany stimulated by the teaching of Carl Ludwig, and later spread to Britain and then to the United States. The goal was to develop a physicochemical understanding of physiological phenomena. The first International Physiological Congress occurred in 1889 in Switzerland with an emphasis on experimental demonstrations. The XIIIth Congress, the first to be held outside of Europe, took place in Boston, MA, in 1929. It was a watershed meeting and indicated that American physiology had come of age. Meticulously organized, it was the largest congress to date, with over 1,200 participants from more than 40 countries. Getting to the congress was a cultural adventure, especially for the 400 scientists and their families from over 20 European countries, who sailed for 10 days on the S.S. Minnekahda. Many of the great physiologists of the world were in attendance, including 22 scientists who were either or would become Nobel Laureates. There were hundreds of platform presentations and many experimental demonstrations. The meeting was not without controversy as a conflict, still not completely settled, arose over the discovery of ATP. After the meeting, hundreds of participants made a memorable trip to the Marine Biological Laboratory at Woods Hole, MA, which culminated in a "good old fashioned Cape Cod Clambake." Although not as spectacular as the 1929 congress, the physiological congresses have continued with goals similar to those established more than a century ago. PMID- 26847253 TI - Learning theories 101: application to everyday teaching and scholarship. AB - Shifts in educational research, in how scholarship in higher education is defined, and in how funding is appropriated suggest that educators within basic science fields can benefit from increased understanding of learning theory and how it applies to classroom practice. This article uses a mock curriculum design scenario as a framework for the introduction of five major learning theories. Foundational constructs and principles from each theory and how they apply to the proposed curriculum designs are described. A summative table that includes basic principles, constructs, and classroom applications as well as the role of the teacher and learner is also provided for each theory. PMID- 26847254 TI - Academic performance in human anatomy and physiology classes: a 2-yr study of academic motivation and grade expectation. AB - This project used a nonexperimental design with a convenience sample and studied the relationship between academic motivation, grade expectation, and academic performance in 1,210 students enrolled in undergraduate human anatomy and physiology (HAP) classes over a 2-yr period. A 42-item survey that included 28 items of the adapted academic motivation scale for HAP based on self determination theory was administered in class during the first 3 wk of each semester. Students with higher grade point averages, who studied for longer hours and reported to be more motivated to succeed, did better academically in these classes. There was a significant relationship between students' scores on the adapted academic motivation scale and performance. Students were more extrinsically motivated to succeed in HAP courses than intrinsically motivated to succeed, and the analyses revealed that the most significant predictor of final grade was within the extrinsic scale (introjected and external types). Students' motivations remained stable throughout the course sequence. The data showed a significant relationship between HAP students' expected grade and their final grade in class. Finally, 65.5% of students overestimated their final grade, with 29% of students overestimating by two to four letter grades. PMID- 26847255 TI - Positive outcomes increase over time with the implementation of a semiflipped teaching model. AB - The flipped teaching model can engage students in the learning process and improve learning outcomes. The purpose of the present study was to assess the outcomes of a semiflipped teaching model over time. Neurophysiology students spent the majority of class time listening to traditional didactic lectures, but they also listened to 5 online lectures and spent 8-10 class periods completing an active learning assignment. At the end of the term, students completed a survey to assess the outcomes of the active learning assignments. The positive outcomes were greater the second time the course was taught in a semiflipped manner. While completely flipping a course takes a tremendous amount of time, instructors can still obtain positive outcomes by implementing a semiflipped teaching model. PMID- 26847256 TI - Doing peer review and receiving feedback: impact on scientific literacy and writing skills. AB - Doing peer review has been effectively implemented to help students develop critical reading and writing skills; however, its application in Human Physiology programs is limited. The purpose of the present study was to determine the impact of peer review on Human Physiology majors' perceptions of their scientific literacy and writing skills. Students enrolled in the Scientific Writing course completed multiple writing assignments, including three revisions after receiving peer and instructor feedback. Students self-assessed their knowledge, skills, and attitudes related to science and writing in pre- and postcourse surveys (n = 26 with complete data). Seven survey items related to scientific literacy and writing skills impacted by peer review were selected for analysis. Scores on these survey items were summed to form a composite self-rating score. Responses to two questions regarding the most useful learning activities were submitted to frequency analysis. Mean postcourse scores for individual survey items and composite self-rating scores were significantly higher than precourse means (P < 0.05). Peer review was the most frequently noted among 21 learning activities for increasing scientific literacy and in the top 5 for improving writing skills. In conclusion, peer review is an effective teaching/learning approach for improving undergraduate Human Physiology majors' knowledge, skills, and attitudes regarding science and scientific writing. PMID- 26847257 TI - Flipped classrooms and student learning: not just surface gains. AB - The flipped classroom is a relatively new approach to undergraduate teaching in science. This approach repurposes class time to focus on application and discussion; the acquisition of basic concepts and principles is done on the students' own time before class. While current flipped classroom research has focused on student preferences and comparative learning outcomes, there remains a lack of understanding regarding its impact on students' approaches to learning. Focusing on a new flipped classroom-based course for basic medical sciences students, the purpose of the present study was to evaluate students' adjustments to the flipped classroom, their time on task compared with traditional lectures, and their deep and active learning strategies. Students in this course worked through interactive online learning modules before in-class sessions. Class time focused on knowledge application of online learning module content through active learning methods. Students completed surveys and optional prequiz questions throughout the term to provide data regarding their learning approaches. Our results showed that the majority of students completed their prework in one sitting just before class. Students reported performing less multitasking behavior in the flipped classroom compared with lecture-based courses. Students valued opportunities for peer-peer and peer-instructor interactions and also valued having multiple modes of assessment. Overall, this work suggests that there is the potential for greater educational gains from the flipped classroom than the modest improvements in grades previously demonstrated in the literature; in this implementation of the flipped classroom, students reported that they developed independent learning strategies, spent more time on task, and engaged in deep and active learning. PMID- 26847258 TI - The Integrated Clinical Anatomy Program at Alfaisal University: an innovative model of teaching clinically applied functional anatomy in a hybrid curriculum. AB - Anatomy has historically been a cornerstone in medical education regardless of specialty. It is essential for physicians to be able to perform a variety of tasks, including performing invasive procedures, examining radiological images, performing a physical examination of a patient, etc. Medical students have to be prepared for such tasks, and we can assist this by changing the way that we educate students in medical schools. Thus, newer medical curricula need to be designed according to needs of future physicians. In this report, we describe a unique program called the Integrated Clinical Anatomy Program (ICAP). The ICAP was developed at the College of Medicine of Alfaisal University in the Kingdom of Saudi Arabia. Here, we describe the unique features of this program, including the structure and facilities of the Anatomy Resource Center. The Anatomy Resource Center plays a pivotal role in engaging the students for faculty-directed structured laboratory sessions as well as peer-assisted uniform student-centered learning. The ICAP has shown great promise, as reflected by early results from a nationwide progress test. Students from all years of the Alfaisal University medical school scored significantly higher than the national average on the anatomy and physiology component of the nationwide progress test examination, with P values of 0.0179 and 0.0015, respectively. We believe that the ICAP can be used as a model for teaching clinically applied functional anatomy to medical students in a hybrid curriculum around the world. PMID- 26847259 TI - Blended learning within an undergraduate exercise physiology laboratory. AB - In physiological education, blended course formats (integration of face-to-face and online instruction) can facilitate increased student learning, performance, and satisfaction in classroom settings. There is limited evidence on the effectiveness of using blending course formats in laboratory settings. We evaluated the impact of blended learning on student performance and perceptions in an undergraduate exercise physiology laboratory. Using a randomized, crossover design, four laboratory topics were delivered in either a blended or traditional format. For blended laboratories, content was offloaded to self-paced video demonstrations (~15 min). Laboratory section 1 (n = 16) completed blended laboratories for 1) neuromuscular power and 2) blood lactate, whereas section 2 (n = 17) completed blended laboratories for 1) maximal O2 consumption and 2) muscle electromyography. Both sections completed the same assignments (scored in a blinded manner using a standardized rubric) and practicum exams (evaluated by two independent investigators). Pre- and postcourse surveys were used to assess student perceptions. Most students (~79%) watched videos for both blended laboratories. Assignment scores did not differ between blended and traditional laboratories (P = 0.62) or between sections (P = 0.91). Practicum scores did not differ between sections (both P > 0.05). At the end of the course, students' perceived value of the blended format increased (P < 0.01) and a greater percentage of students agreed that learning key foundational content through video demonstrations before class greatly enhanced their learning of course material compared with a preassigned reading (94% vs. 78%, P < 0.01). Blended exercise physiology laboratories provided an alternative method for delivering content that was favorably perceived by students and did not compromise student performance. PMID- 26847260 TI - Use of metabolomics for the chemotaxonomy of legume-associated Ascochyta and allied genera. AB - Chemotaxonomy and the comparative analysis of metabolic features of fungi have the potential to provide valuable information relating to ecology and evolution, but have not been fully explored in fungal biology. Here, we investigated the chemical diversity of legume-associated Ascochyta and Phoma species and the possible use of a metabolomics approach using liquid chromatography-mass spectrometry for their classification. The metabolic features of 45 strains including 11 known species isolated from various legumes were extracted, and the datasets were analyzed using chemometrics methods such as principal component and hierarchical clustering analyses. We found a high degree of intra-species consistency in metabolic profiles, but inter-species diversity was high. Molecular phylogenies of the legume-associated Ascochyta/Phoma species were estimated using sequence data from three protein-coding genes and the five major chemical groups that were detected in the hierarchical clustering analysis were mapped to the phylogeny. Clusters based on similarity of metabolic features were largely congruent with the species phylogeny. These results indicated that evolutionarily distinct fungal lineages have diversified their metabolic capacities as they have evolved independently. This whole metabolomics approach may be an effective tool for chemotaxonomy of fungal taxa lacking information on their metabolic content. PMID- 26847262 TI - From bedside to the bench: uncovering the role of a T-cell protein in protecting CTLA-4. PMID- 26847261 TI - A high-throughput pipeline for the production of synthetic antibodies for analysis of ribonucleoprotein complexes. AB - Post-transcriptional regulation of mRNAs plays an essential role in the control of gene expression. mRNAs are regulated in ribonucleoprotein (RNP) complexes by RNA-binding proteins (RBPs) along with associated protein and noncoding RNA (ncRNA) cofactors. A global understanding of post-transcriptional control in any cell type requires identification of the components of all of its RNP complexes. We have previously shown that these complexes can be purified by immunoprecipitation using anti-RBP synthetic antibodies produced by phage display. To develop the large number of synthetic antibodies required for a global analysis of RNP complex composition, we have established a pipeline that combines (i) a computationally aided strategy for design of antigens located outside of annotated domains, (ii) high-throughput antigen expression and purification in Escherichia coli, and (iii) high-throughput antibody selection and screening. Using this pipeline, we have produced 279 antibodies against 61 different protein components of Drosophila melanogaster RNPs. Together with those produced in our low-throughput efforts, we have a panel of 311 antibodies for 67 RNP complex proteins. Tests of a subset of our antibodies demonstrated that 89% immunoprecipitate their endogenous target from embryo lysate. This panel of antibodies will serve as a resource for global studies of RNP complexes in Drosophila. Furthermore, our high-throughput pipeline permits efficient production of synthetic antibodies against any large set of proteins. PMID- 26847263 TI - Ribosomal protein S15A promotes malignant transformation and predicts poor outcome in colorectal cancer through misregulation of p53 signaling pathway. AB - Ribosomal protein S15A (RPS15A), which has been identified as a highly conserved 40S ribosomal protein, is essential for cell survival and proliferation. The present study evaluated the functional role of RPS15A in colorectal cancer (CRC), and our investigation found that RPS15A was highly expressed in a cohort of human CRC. High RPS15A expression was associated with older age (P=0.035), not receiving preoperative neoadjuvant treatment (P=0.048), higher primary pN stage (P=0.007) and slightly more synchronous distant metastases (P=0.058). The Cox univariate and multivariate hazard regression analysis revealed that higher expression of RPS15A led to a reduction of overall survival rate in CRC, indicating that enhanced RPS15A expression functions as an independent risk factor for the prognosis of CRC patients (P<0.001). Cell based analysis showed that RPS15A was widely expressed in human CRC cell lines. Knockdown of RPS15A significantly suppressed cell proliferation and colony formation in HCT116 and DLD-1 cells, and induced cell cycle arrest at G0/G1 phase. Genechip analysis suggested that knockdown of RPS15A might affect the p53 signaling pathway. Further study indicated that RPS15A knockdown upregulated p53 and p21 expression whereas downregulated CDK1 expression. In summary, the present study identified RPS15A as a novel univariate prognostic factor predicting a poor outcome in CRC patients. The RPS15A overexpression induced by malignant transformation of CRC might function through the p53 signaling pathway. PMID- 26847264 TI - Risk profile of patients developing nonunion of the clavicle and outcome of treatment--analysis of fifty five nonunions in seven hundred and twenty nine consecutive fractures. AB - PURPOSE: The most common complication following treatment of a clavicle fracture is nonunion. Most nonunions are symptomatic and treatment is mostly operative. The aim of this study was to describe risk profiles of patients developing nonunion and what outcome is observed following operative treatment of clavicle nonunions. METHODS: In a consecutive series of 729 clavicle fractures we retrospectively identified 55 that developed nonunion (49 diaphysial and six lateral). All were treated operatively by reconstruction with (n = 28) or without (n = 27) autologous bone graft. Assessment of functionality and patient reported satisfaction and remission of symptoms was done a minimum of six months post operatively by mail. Response rate was 60%. RESULTS: The overall nonunion rate was 7.5%. Nine nonunions were initially treated operatively. Risk factors associated with nonunion of our series was anatomic site, fracture complexity, female gender, smoking habits and initial treatment. A total of eight post operative complications were found. Remission of symptoms was reported by 29 of the 33. Outright satisfaction with current shoulder condition was reported by 24. The overall median DASH was 8 (range 0-61). Following revision of the eight complications a total of 53 united successfully. CONCLUSION: Operative treatment of a clavicular nonunion seems to be effective as most patients unite and experience remission of symptoms. However, complications in close to 15% and lack of satisfaction of approximately 27% have to be acknowledged and thoroughly explained to the patient prior to treatment. PMID- 26847265 TI - Review article: sarcopenia in cirrhosis--aetiology, implications and potential therapeutic interventions. AB - BACKGROUND: Sarcopenia (loss of muscle mass) is common in cirrhosis and is associated with poor outcomes. Current teaching recommends the use of protein supplementation and exercise, however, this fails to address many other factors which contribute to muscle loss in this setting. AIMS: To summarise existing knowledge regarding the aetiology of sarcopenia in cirrhosis, diagnostic modalities and the clinical significance of this condition. In addition to discuss recent research findings that may allow the development of more effective treatments. METHODS: We conducted a Medline and PubMed search using the search terms 'sarcopenia', 'muscle', 'body composition', 'cirrhosis', 'liver' and 'malnutrition' from inception to October 2015. RESULTS: Cirrhotic patients with sarcopenia have reduced survival, experience increased rates of infection and have worse outcomes following liver transplantation. The aetiology of this condition is more complex than simple protein and calorie malnutrition. Cirrhosis also results in depleted glycogen stores and metabolic alterations that cause excessive protein catabolism, increased activation of the ubiquitin-proteasome pathway and inappropriate muscle autophagy. Satellite cell differentiation and proliferation is also reduced due to a combination of elevated myostatin levels, reduced IGF-1 and hypogonadism. Although there is some evidence supporting the use of late evening snacks, branched chain amino acid supplementation and high protein/high calorie diets, well designed clinical trials addressing the effects of treatment on body composition in cirrhosis are lacking. CONCLUSION: Sarcopenia in cirrhosis has a complex pathogenesis and simple dietary interventions are insufficient. Improved understanding of the multiple mechanisms involved should allow the development of more effective therapies, which target the specific underlying metabolic derangements. PMID- 26847267 TI - Novel quantum description for nonadiabatic evolution of light wave propagation in time-dependent linear media. AB - A simple elegant expression of nonadiabatic light wave evolution is necessary in order to have a deeper insight for complicated optical phenomena in light science as well as in everyday life. Light wave propagation in linear media which have time-dependent electromagnetic parameters is investigated by utilizing a quadratic invariant of the system. The time behavior of the nonadiabatic geometric phase of the waves that yield a cyclic nonadiabatic evolution is analyzed in detail. Various quantum properties of light waves in this situation, such as variances of electric and magnetic fields, uncertainty product, coherent and squeezed states, and their classical limits, are developed. For better understanding of our research, we applied our analysis in a particular case. The variances of the fields D and B are illustrated and their time behaviors are addressed. Equivalent results for the corresponding classical systems are deduced from the study of the time evolution of the appropriate coherent and squeezed states. PMID- 26847268 TI - Zapotin (5,6,2',6'-tetramethoxyflavone) Modulates the Crosstalk Between Autophagy and Apoptosis Pathways in Cancer Cells with Overexpressed Constitutively Active PKCepsilon. AB - Autophagy is important in the regulation of survival and death signaling pathways in cancer. PKCepsilon revealed high transforming potential and the ability to increase cell migration, invasion, and metastasis. Zapotin (5,6,2',6' tetramethoxyflavone), a natural flavonoid, showed chemopreventive and anticancer properties. Previously, we reported that downmodulation of induced PKCepsilon level by zapotin was associated with decreased migration and increased apoptosis in HeLa cell line containing doxycycline-inducible constitutively active PKCepsilon (PKCepsilonA/E, Ala(159) -> Glu). Depending on the genetic and environmental content of cells, autophagy may either precede apoptosis or occur simultaneously. The purpose of this study was to assess the effect of zapotin on autophagy. Increasing concentration of zapotin (from 7.5 uM to 30 uM) caused an inhibition of the formation of autophagosomes and a decline in microtubule associated protein 1 light chain 3 (LC3) protein levels. The gene expression level of major negative regulator of autophagy was noticeably increased. Moreover, the expression of the pivotal autophagy genes was decreased. These changes were accompanied by alternation in autophagy-related protein levels. In conclusion, our results implied that both the antiautophagic and the proapoptosis effect of zapotin in HeLaPKCepsilonA/E cells are associated with the protein kinase C epsilon signaling pathway and lead to programmed cell death. PMID- 26847269 TI - [Not Available]. PMID- 26847266 TI - Dark microglia: A new phenotype predominantly associated with pathological states. AB - The past decade has witnessed a revolution in our understanding of microglia. These immune cells were shown to actively remodel neuronal circuits, leading to propose new pathogenic mechanisms. To study microglial implication in the loss of synapses, the best pathological correlate of cognitive decline across chronic stress, aging, and diseases, we recently conducted ultrastructural analyses. Our work uncovered the existence of a new microglial phenotype that is rarely present under steady state conditions, in hippocampus, cerebral cortex, amygdala, and hypothalamus, but becomes abundant during chronic stress, aging, fractalkine signaling deficiency (CX3 CR1 knockout mice), and Alzheimer's disease pathology (APP-PS1 mice). Even though these cells display ultrastructural features of microglia, they are strikingly distinct from the other phenotypes described so far at the ultrastructural level. They exhibit several signs of oxidative stress, including a condensed, electron-dense cytoplasm and nucleoplasm making them as "dark" as mitochondria, accompanied by a pronounced remodeling of their nuclear chromatin. Dark microglia appear to be much more active than the normal microglia, reaching for synaptic clefts, while extensively encircling axon terminals and dendritic spines with their highly ramified and thin processes. They stain for the myeloid cell markers IBA1 and GFP (in CX3 CR1-GFP mice), and strongly express CD11b and microglia-specific 4D4 in their processes encircling synaptic elements, and TREM2 when they associate with amyloid plaques. Overall, these findings suggest that dark microglia, a new phenotype that we identified based on their unique properties, could play a significant role in the pathological remodeling of neuronal circuits, especially at synapses. PMID- 26847270 TI - [Comparison of conventional culture methods and quantitative real-time PCR methods for the detection of Legionella pneumophila in water samples in a large University teaching hospital in Rome, Italy]. AB - The aims of this study were to identify the best threshold value for the real time PCR method in detecting the presence of Legionella pneumophila in water samples, and to evaluate the prognostic significance of negative results obtained with the molecular method. From 2011 to 2014, 77 water samples were collected from hospital wards of a large University teaching hospital in Rome (Italy) and screened for L.pneumophila by the standard culture method and by real-time PCR. The high sensitivity and negative predictive value of real-time PCR make this method suitable as a quick screening tool to exclude the presence of L. pneumophila in water samples in the hospital setting. PMID- 26847271 TI - [The Day Service as a tool to reduce inappropriateness of care: the experience of a research hospital in Rome (Italy)]. AB - The Day Service was established in Italy to promote appropriateness of care and consists in the delivery of packages of complex outpatient services. A Working Group for the continuous improvement of pre-hospitalization activities of the Regina Elena Scientific Institute in Rome, Italy, established that the outpatient management of surgical patients in the hospital would occur in a Day Service, through a package of services identified at the regional level or appropriate diagnostic and therapeutic pathways. This article describes the experience of the hospital's Day Service and compares results from the last four months of 2013 with those of the first four months of 2014. The introduction of a Day Service has led to a reduction in the number of inappropriate pre-admission tests (mainly computerized tomography, magnetic resonance and Positron emission scans and scintigraphy) and this has had a positive impact not only in terms of organization, reduction of hospital stay and overall hospitalization-related activities, but also from an economic standpoint. The implementation of a Day Service has also improved the overall patient experience, from an organizational point of view, and this is an important aspect, considering that patients at the Regina Elena Scientific Institute are oncological patients, they are often elderly and most reside in other Italian regions. PMID- 26847272 TI - [Evaluation of the antimicrobial activity of products used for disinfection of work surfaces in the food industry]. AB - Disinfection of work surfaces is a critical step in the food industry. In this study, we evaluated the antimicrobial efficacy of four commercial products against target pathogens, using the suspension test indicated in the European Standard EN 1276: 2009. The data obtained indicate that the product containing benzalkonium chloride ("A") was the most effective with a logarithmic reduction > 5 against all microorganisms after 5 minutes of contact in simulated dirty and clean conditions. Efficacy of the product based on sodium hypochlorite ("B") was dependent on the experimental conditions applied, while for products containing hydrogen peroxide and citric acid ("C" and "D" respectively), 15 min of contact were required, in both the experimental conditions, to obtain a logarithmic reduction> 5. Exposure time to disinfectants and applied conditions appear to be important in reducing bacterial load to safe levels in the food industry. PMID- 26847273 TI - [Imported malaria in Sicily (Italy): epidemiology and recommendations for prevention]. AB - This study analysed cases of imported malaria notified to the District Health Units of Palermo from 1998 to 2014. The aim was to assess epidemiological differences among cases, related to their reasons for travel. Eighty one cases were reported: 83% developed symptoms following a trip to Africa while 17% had travelled to Asia. Seventy-three percent of cases had travelled to visit family or friends in malaria-endemic countries (Visiting Friends and Relatives: VFRs), confirming the need for preventive measures targeted towards this at-risk population group. PMID- 26847274 TI - [How to manage disasters: learning from recent experiences in the Emergency Department of a University Teaching Hospital, Italy]. AB - The medical approach to disasters has been always a problematic issue for emergency departments. The authors of this paper reflect on possible efficient solutions for managing a massive influx of casualties in an Emergency Department, by analysing the responses to previous local catastrophic events, such as the collision of 'Segesta Jet', the great fire of Patti, the floods of Giampilieri/Scaletta and Saponara. The authors' point to a need for providing more extensive training of medical students in clinical aspects of disaster medicine. PMID- 26847275 TI - [Prevention of HPV cancer related through HPV-9: state of the art, potential benefits and open issues]. AB - HPV vaccines currently marketed in Italy (bivalent and quadrivalent against HPV 16-18 and HPV and 6,11,16,18 respectively) are an extraordinary tool for the primary prevention of HPV related diseases, particularly of the cervical cancer. Although the implementation of the organized vaccination programs has already translated (for some endpoint) in confirmation of clinical efficacy, remains excluded a significant proportion of the diseases linked to non-vaccine HPV types. The new nonavalent vaccine (HPV9), of impending commercialization, represents an evolution of the quadrivalent, the composition of which are added five high-risk HPV types (HPV 31,33,45,52,58). The high clinical-immunological efficacy in experimental trials against the new genotypes (> 96% for CIN2 +), and the equivalence immunogenic to the four already present in the previous vaccine, will render the use of HPV9 a tool able to control in an even more effective HPV disease. The potential of the new vaccine is linked to the reduction of the HPV cancer burden by 2-20% according to anatomical site, with major benefits for cervical cancer, vulvo-vaginal, penile and more limited benefits for anal tumours. Moreover, the potential benefits could be also linked to the reduction of incidence of pre-neoplastic lesions arising in the lower-genital tract, especially in the cervix (CIN2-3), so often cause lengthy and expensive diagnostic and therapeutic procedures. In the face of this broad provision of benefit from HPV9 vaccine, we have also to consider all the variables related to its introduction in the vaccination calendars: the market price, the schedule of administration (currently in three doses) and data regarding the cost effectiveness. The authors recognize the new vaccine (currently registered only in the US) a lot of potential in the prevention of HPV-related diseases. PMID- 26847276 TI - Early Roots of Western Medicine and a Pioneer of Social Work in Korea: Dr. Kung Sun Oh (1878-1963). PMID- 26847277 TI - A Simple, Reproducible, Inexpensive, Yet Old-Fashioned Method for Determining Phagocytic and Bactericidal Activities of Macrophages. AB - Macrophages (Mphi) play a pivotal role in the protection system by recognizing and eliminating invading pathogenic bacteria. Phagocytosis and the killing of invading bacteria are major effector functions of Mphi. Although the phagocytic and bactericidal activities of Mphi have been analyzed via several methods using a light microscope, a fluorescence microscope, or a fluorescence-activated cell sorter, expensive materials and equipment are usually required, and the methods are rather complicated. Moreover, it is impossible to determine both the phagocytic and bactericidal activities of Mphi simultaneously using these methods. In this review, we describe a simple, reproducible, inexpensive, yet old fashioned method (antibiotic protection assay) for determining the phagocytic and bactericidal activities of Mphi. PMID- 26847278 TI - Therapeutic Hypothermia for Cardioprotection in Acute Myocardial Infarction. AB - Mild therapeutic hypothermia of 32-35 degrees C improved neurologic outcomes in outside hospital cardiac arrest survivor. Furthermore, in experimental studies on infarcted model and pilot studies on conscious patients with acute myocardial infarction, therapeutic hypothermia successfully reduced infarct size and microvascular resistance. Therefore, mild therapeutic hypothermia has received an attention as a promising solution for reduction of infarction size after acute myocardial infarction which are not completely solved despite of optimal reperfusion therapy. Nevertheless, the results from randomized clinical trials failed to prove the cardioprotective effects of therapeutic hypothermia or showed beneficial effects only in limited subgroups. In this article, we reviewed rationale for therapeutic hypothermia and possible mechanisms from previous studies, effective methods for clinical application to the patients with acute myocardial infarction, lessons from current clinical trials and future directions. PMID- 26847279 TI - The Expression of MicroRNA-155 in Plasma and Tissue Is Matched in Human Laryngeal Squamous Cell Carcinoma. AB - PURPOSE: Tumor-associated microRNAs have been detected in cancer, though whether plasma microRNA-155 (miR-155) could be a potential biomarker for laryngeal squamous cell carcinoma (LSCC) prognosis is unclear. We aimed to determine how miR-155 can be used to predict the clinical characteristics of patients with LSCC and correctly diagnose them. MATERIALS AND METHODS: We collected tissue samples and peripheral blood samples before and after treatment from 280 LSCC cases and 560 controls. Real-time quantitative reverse transcription PCR was employed in this study to compare the relative expression of miR-155. RESULTS: A total of 280 LSCC patients and 560 age- and sex-matched controls were included in the study. The miR-155 level was more up-regulated in LSCC tissue than in the non-tumor tissues (13.6 +/- 2.4 vs. 3.1 +/- 0.80, p<0.001). Additionally, a significantly higher miR-155 level in plasma samples from LSCC patients than in those of the controls (8.9 +/- 1.25 vs. 1.8 +/- 0.8, p<0.001) was reported. Tissue miR-155 showed an area under the curve (AUC) of 0.933, with a sensitivity of 82.6% and a specificity of 89.2%. The AUC for plasma miR-155 was 0.757, with a sensitivity of 58.4% and a specificity of 69.5%. When early LSCC in TNM I stage was considered, tissue miR-155 showed an area under the curve of 0.804, with a sensitivity of 85.2% and a specificity of 87.3%. CONCLUSION: The expression of tissue and plasma miR-155 were significantly up-regulated in patients with LSCC. Our work will serve as a basis for further investigation, preferably large-scale validation in clinical trials. PMID- 26847280 TI - Hemodynamic Follow-Up in Adult Patients with Pulmonary Hypertension Associated with Atrial Septal Defect after Partial Closure. AB - PURPOSE: We evaluated the hemodynamic statuses of patients after partial closure of atrial septal defects with fenestration due to pulmonary hypertension. MATERIALS AND METHODS: Seventeen adult patients underwent partial atrial septal defect closure and follow-up cardiac catheterization. We analyzed hemodynamic data and clinical parameters before and after closure. RESULTS: The median age at closure was 29 years old. The baseline Qp/Qs was 1.9 +/- 0.6. The median interval from the operation to the cardiac catheterization was 27 months. The CT ratio decreased from 0.55 +/- 0.07 to 0.48 +/- 0.06 (p<0.05). The mean pulmonary arterial pressure decreased from 50.0 +/- 11.5 mm Hg to 32.5 +/- 14.4 mm Hg (p<0.05), and the pulmonary resistance index decreased from 9.2 +/- 3.6 Wood units*m2 to 6.3 +/- 3.8 Wood units*m2 (p<0.05). Eleven patients (64.7%) continued to exhibit high pulmonary resistance (over 3.0 Wood units*m2) after closure. These patients had significantly higher pulmonary resistance indices and mean pulmonary arterial pressures based on oxygen testing before the partial closures (p<0.05). However, no significant predictors of post-closure pulmonary hypertension were identified. CONCLUSION: Despite improvement in symptoms and hemodynamics after partial closure of an atrial septal defect, pulmonary hypertension should be monitored carefully. PMID- 26847281 TI - Role of Baroreflex Sensitivity in Predicting Tilt Training Response in Patients with Neurally Mediated Syncope. AB - PURPOSE: An association between baroreflex sensitivity (BRS) and the response to tilt training has not been reported in patients with neurally mediated syncope (NMS). This study sought to investigate the role of BRS in predicting the response to tilt training in patients with NMS. MATERIALS AND METHODS: We analyzed 57 patients who underwent tilt training at our hospital. A responder to tilt training was defined as a patient with three consecutive negative responses to the head-up tilt test (HUT) during tilt training. RESULTS: After tilt training, 52 patients (91.2%) achieved three consecutive negative responses to the HUT. In the supine position before upright posture during the first session of tilt training for responders and non-responders, the mean BRS was 18.17 +/- 10.09 ms/mm Hg and 7.99 +/- 5.84 ms/mm Hg (p=0.008), respectively, and the frequency of BRS >= 8.945 ms/mm Hg was 45 (86.5%) and 1 (20.0%; p=0.004), respectively. Age, male gender, frequency of syncopal events before HUT, type of NMS, phase of positive HUT, total number of tilt training sessions, and mean time of tilt training did not differ between the study groups. In the multivariate analysis, BRS <8.945 ms/mm Hg in the supine position (odds ratio 23.10; 95% CI 1.20-443.59; p=0.037) was significantly and independently associated with non response to tilt training. CONCLUSION: The BRS value in the supine position could be a predictor for determining the response to tilt training in patients with NMS who are being considered for inpatient tilt training. PMID- 26847283 TI - Prosthesis-Patient Mismatch after Mitral Valve Replacement: Comparison of Different Methods of Effective Orifice Area Calculation. AB - PURPOSE: The incidence of prosthesis-patient mismatch (PPM) after mitral valve replacement (MVR) has been reported to vary. The purpose of the current study was to investigate incidence of PPM according to the different methods of calculating effective orifice area (EOA), including the continuity equation (CE), pressure half time (PHT) method and use of reference EOA, and to compare these with various echocardiographic variables. MATERIALS AND METHODS: We retrospectively reviewed 166 individuals who received isolated MVR due to rheumatic mitral stenosis and had postoperative echocardiography performed between 12 and 60 months after MVR. EOA was determined by CE (EOA(CE)) and PHT using Doppler echocardiography. Reference EOA was determined from the literature or values offered by the manufacturer. Indexed EOA was used to define PPM as present if <=1.2 cm2/m2. RESULTS: Prevalence of PPM was different depending on the methods used to calculate EOA, ranging from 7% in PHT method to 49% in referred EOA method to 62% in CE methods. The intraclass correlation coefficient was low between the methods. PPM was associated with raised trans-prosthetic pressure, only when calculated by CE (p=0.021). Indexed EOA(CE) was the only predictor of postoperative systolic pulmonary artery (PA) pressure, even after adjusting for age, preoperative systolic PA pressure and postoperative left atrial volume index (p<0.001). CONCLUSION: Prevalence of mitral PPM varied according to the methods used to calculate EOA in patients with mitral stenosis after MVR. Among the various methods used to define PPM, EOA(CE) was the only predictor of postoperative hemodynamic parameters. PMID- 26847282 TI - Darapladib, a Lipoprotein-Associated Phospholipase A2 Inhibitor, Reduces Rho Kinase Activity in Atherosclerosis. AB - PURPOSE: Increased lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and Rho kinase activity may be associated with atherosclerosis. The principal aim of this study was to examine whether darapladib (a selective Lp-PLA2 inhibitor) could reduce the elevated Lp-PLA2 and Rho kinase activity in atherosclerosis. MATERIALS AND METHODS: Studies were performed in male Sprague-Dawley rats. The atherosclerosis rats were prepared by feeding them with a high-cholesterol diet for 10 weeks. Low-dose darapladib (25 mg.kg-1.d-1) and high-dose darapladib (50 mg.kg-1.d-1) interventions were then administered over the course of 2 weeks. RESULTS: The serum levels of triglycerides, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), high-sensitivity C-reactive protein (hs-CRP), and Lp-PLA2, significantly increased in atherosclerosis model groups, as did Rho kinase activity and cardiomyocyte apoptosis (p<0.05 vs. sham group), whereas nitric oxide (NO) production was reduced. Levels of TC, LDL-C, CRP, Lp-PLA2, and Rho kinase activity were respectively reduced in darapladib groups, whereas NO production was enhanced. When compared to the low-dose darapladib group, the reduction of the levels of TC, LDL-C, CRP, and Lp-PLA2 was more prominent in the high-dose darapladib group (p<0.05), and the increase of NO production was more prominent (p<0.05). Cardiomyocyte apoptosis of the high-dose darapladib group was also significantly reduced compared to the low-dose darapladib group (p<0.05). However, there was no significant difference in Rho kinase activity between the low-dose darapladib group and the high-dose darapladib group (p>0.05). CONCLUSION: Darapladib, a Lp-PLA2 inhibitor, leads to cardiovascular protection that might be mediated by its inhibition of both Rho kinase and Lp-PLA2 in atherosclerosis. PMID- 26847284 TI - Comparison of Paclitaxel-Coated Balloon Treatment and Plain Old Balloon Angioplasty for De Novo Coronary Lesions. AB - PURPOSE: This study compared the angiographic outcomes of paclitaxel-coated balloon (PCB) versus plain old balloon angioplasty (POBA) treatment for de novo coronary artery lesions. At present, there is no available data comparing the efficacy of PCB versus POBA for the treatment of de novo coronary lesions. MATERIALS AND METHODS: This multicenter retrospective observational study enrolled patients with de novo coronary lesions with a reference vessel diameter between 2.5 mm and 3.0 mm and lesion length <= 24 mm who were successfully treated with PCB or POBA. Angiographic measurements and quantitative coronary analysis were performed before and after the procedure, and at 9 months follow up. RESULTS: A total of 72 patients (49 receiving PCB and 23 receiving POBA) were enrolled in this study. Late luminal loss was -0.12 +/- 0.30 mm in the PCB group and 0.25 +/- 0.50 mm in the POBA group (p<0.001). There was a higher percentage of binary restenosis (diameter stenosis >= 50%) in POBA, compared to PCB (30.4%, n=7 vs. 4.1%, n=2, p<0.001). Target vessel revascularization was higher in the POBA group (13.0%, n=3 vs. 0%, p=0.033). CONCLUSION: PCB treatment of de novo coronary lesions showed better 9-month angiographic outcomes than POBA treatment alone. PMID- 26847285 TI - Early Experience of Novel Oral Anticoagulants in Catheter Ablation for Atrial Fibrillation: Efficacy and Safety Comparison to Warfarin. AB - PURPOSE: Compared with warfarin, novel oral anticoagulants (NOACs) are convenient to use, although they require a blanking period immediately before radiofrequency catheter ablation for atrial fibrillation (AF). We compared NOACs and uninterrupted warfarin in the peri-procedural period of AF ablation. MATERIALS AND METHODS: We compared 141 patients treated with peri-procedural NOACs (72% men; 58 +/- 11 years old; 71% with paroxysmal AF) and 281 age-, sex-, AF type-, and history of stroke-matched patients treated with uninterrupted warfarin. NOACs were stopped 24 hours before the procedure and restarted on the same procedure day after hemostasis was achieved. RESULTS: We found no difference in the CHA2DS2 VASc (p=0.376) and HAS-BLED scores (p=0.175) between the groups. The preprocedural anticoagulation duration was significantly shorter in the NOAC group (76.3 +/- 110.7 days) than in the warfarin group (274.7 +/- 582.7 days, p<0.001). The intra-procedural total heparin requirement was higher (p<0.001), although mean activated clotting time was shorter (350.0 +/- 25.0 s vs. 367.4 +/- 42.9 s, p<0.001), in the NOAC group than in the warfarin group. There was no significant difference in thromboembolic events (1.4% vs. 0%, p=0.111) or major bleeding (1.4% vs. 3.9%, p=0.235) between the NOAC and warfarin groups. Minor stroke occurred in two cases within 10 hours of the procedure (underlying CHA2DS2 VASc scores 0 and 1) in the NOAC group. CONCLUSION: Pre-procedural anticoagulation duration was shorter and intra-procedural heparin requirement was higher with NOAC than with uninterrupted warfarin during AF ablation. Although the peri-procedural thromboembolism and bleeding incidences did not differ, minor stroke occurred in two cases in the NOAC group. PMID- 26847286 TI - Increasing Incidence of High-Level Tetracycline-Resistant Neisseria gonorrhoeae due to Clonal Spread and Foreign Import. AB - PURPOSE: The detection of high-level tetracycline-resistant strains of Neisseria gonorrhoeae (TRNG) can make important epidemiological contributions that are relevant to controlling infections from this pathogen. In this study, we aimed to determine the incidence of TRNG isolates over time and also to investigate the characteristics and genetic epidemiology of these TRNG isolates in Korea. MATERIALS AND METHODS: The antimicrobial susceptibilities of 601 isolates of N. gonorrhoeae from 2004 to 2011 were tested by standard Clinical and Laboratory Standards Institute methods. To determine the molecular epidemiological relatedness, N. gonorrhoeae multi-antigen sequence typing was performed. RESULTS: The incidence of TRNG increased from 2% in 2004 to 21% in 2011. The minimum inhibitory concentration distributions of ceftriaxone and susceptibility of ciprofloxacin in TRNG were different from non-TRNG and varied according to the year of isolation. Most of the TRNG isolates collected from 2004 to 2007 exhibited genetic relatedness, with sequence type (ST) 1798 being the most common. From 2008 to 2011, the STs of the isolates became more variable and introduction of genetically unrelated TRNG were noted. CONCLUSION: The increased incidence of TRNG strains until 2007 appears to be due, at least in part, to clonal spread. However, we propose that the emergence of various STs since 2008 could be associated with foreign import. PMID- 26847287 TI - Clinical Prognostic Factors in 86 Chinese Patients with Primary Myelodysplastic Syndromes and Trisomy 8: A Single Institution Experience. AB - PURPOSE: The objective was to determine the characteristics and prognostic factors of 86 Chinese patients with trisomy 8 aberrations and compare the prognostic value of International Prognostic System (IPSS) and Revised IPSS (IPSS R) in this cohort. MATERIALS AND METHODS: A total of 86 cases diagnosed with primary myelodysplastic syndromes (MDS) with isolated tr8 or with tr8 and other additional cytogenetic aberrations diagnosed and treated at the Union Hospital, Tongji Medical College of Huazhong University of Science and Technology between July 2002 and March 2013 were reviewed. RESULTS: The median survival of the entire group was 23.0 months, and acute myeloid leukemia (AML) developed in 43% (37/86) patients within the follow up time. The univariate analysis revealed that overall survival (OS) was correlated with age, thrombocytopenia, absolute neutrophil count, marrow blasts, cytogenetic status and red blood cell transfusion at diagnosis, and the multivariate analysis revealed that age, marrow blasts, cytogenetic status and transfusion dependence were independent parameters for the OS. The cytogenetic complexity and marrow blasts had the strongest impact on the AML transformation by multivariate analysis. Comparing the two prognostic systems, both two systems could successfully discriminate risk groups for survival. IPSS-R was more refined than IPSS for predicting OS, but had no advantage in predicting the risk of AML development. CONCLUSION: This study confirmed the influence of clinical factors on the prognosis of 86 Chinese MDS patients with trisomy 8. In addition, IPSS-R can further refine prognostic discrimination in the IPSS risk categories. PMID- 26847288 TI - Risk Factor and Clinical Outcome of Bronchiolitis Obliterans Syndrome after Allogeneic Hematopoietic Stem Cell Transplantation. AB - PURPOSE: The development of bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic stem cell transplantation (HSCT) deteriorates patients' quality of life. This study aimed to analyze the prevalence, clinical features, risk factors and prognostic factors of BOS. MATERIALS AND METHODS: This retrospective study included patients who underwent allogeneic HSCT from January 2002 to December 2008 and survived for >=100 days after transplantation. RESULTS: Of 860 patients who survived for >=100 days, 36 (4.2%) met the diagnostic criteria. The duration of BOS development after transplantation was 466.00 (284.00-642.75) [median (interquartile range)] days. The risk factor for the development of BOS was peripheral blood as the stem cell source with a hazard ratio (HR) of 2.550 [95% confidence interval (CI): 1.274-5.104, p=0.008]. In multivariate analysis, pretransplant FEV1/FVC (HR: 0.956, 95% CI: 0.921-0.993, p=0.020) and time from HSCT to diagnosis of BOS (HR: 0.997, 95% CI: 0.994-0.999, p=0.009) were independent prognostic factors associated with mortality. CONCLUSION: Peripheral blood as a stem cell source is a risk factor for the development of BOS. A decreased pretransplant FEV1/FVC and shorter duration of time from transplantation to diagnosis of BOS are poor prognostic factors for BOS. PMID- 26847289 TI - Anti-Proliferative Effects of Rutin on OLETF Rat Vascular Smooth Muscle Cells Stimulated by Glucose Variability. AB - PURPOSE: Proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in atherosclerosis. Rutin is a major representative of the flavonol subclass of flavonoids and has various pharmacological activities. Currently, data are lacking regarding its effects on VSMC proliferation induced by intermittent hyperglycemia. Here, we demonstrate the effects of rutin on VSMC proliferation and migration according to fluctuating glucose levels. MATERIALS AND METHODS: Primary cultures of male Otsuka Long-Evans Tokushima Fatty (OLETF) rat VSMCs were obtained from enzymatically dissociated rat thoracic aortas. VSMCs were incubated for 72 h with alternating normal (5.5 mmol/L) and high (25.0 mmol/L) glucose media every 12 h. Proliferation and migration of VSMCs, the proliferative molecular pathway [including p44/42 mitogen-activated protein kinases (MAPK), mitogen-activated protein kinase kinase 1/2 (MEK1/2), p38 MAPK, phosphoinositide 3-kinase (PI3K), c-Jun N-terminal protein kinase (JNK), nuclear factor kappa B (NF-kappaB), and Akt], the migratory pathway (big MAPK 1, BMK1), reactive oxygen species (ROS), and apoptotic pathway were analyzed. RESULTS: We found enhanced proliferation and migration of VSMCs when cells were incubated in intermittent high glucose conditions, compared to normal glucose. These effects were lowered upon rutin treatment. Intermittent treatment with high glucose for 72 h increased the expression of phospho-p44/42 MAPK (extracellular signal regulated kinase 1/2, ERK1/2), phospho-MEK1/2, phospho-PI3K, phospho-NF-kappaB, phospho-BMK1, and ROS, compared to treatment with normal glucose. These effects were suppressed by rutin. Phospho-p38 MAPK, phospho-Akt, JNK, and apoptotic pathways [B-cell lymphoma (Bcl)-xL, Bcl-2, phospho-Bad, and caspase-3] were not affected by fluctuations in glucose levels. CONCLUSION: Fluctuating glucose levels increased proliferation and migration of OLETF rat VSMCs via MAPK (ERK1/2), BMK1, PI3K, and NF-kappaB pathways. These effects were inhibited by the antioxidant rutin. PMID- 26847290 TI - Percutaneous Coronary Intervention Is More Beneficial Than Optimal Medical Therapy in Elderly Patients with Angina Pectoris. AB - PURPOSE: Data comparing the clinical benefits of medical treatment with those of percutaneous coronary intervention (PCI) in an elderly population with angina pectoris are limited. Therefore, we evaluated the efficacy of elective PCI versus optimal medical treatment (OMT) in elderly patients (between 75 and 84 years old) with angina pectoris. MATERIALS AND METHODS: One hundred seventy-seven patients with significant coronary artery stenosis were randomly assigned to either the PCI group (n=90) or the OMT group (n=87). The primary outcome was a composite of major adverse events in the 1-year follow-up period that included cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and stroke. RESULTS: Major adverse events occurred in 5 patients (5.6%) of the PCI group and in 17 patents (19.5%) of the OMT group (p=0.015). There were no significant differences between the PCI group and the OMT group in cardiac death [hazard ratio (HR) for the PCI group 0.454; 95% confidence interval (CI) 0.041-5.019, p=0.520], myocardial infarction (HR 0.399; 95% CI 0.039-4.050, p=0.437), or stroke (HR 0.919; 95% CI 0.057-14.709, p=0.952). However, the PCI group showed a significant preventive effect of the composite of major adverse events (HR 0.288; 95% CI 0.106-0.785, p=0.015) and against the need for coronary revascularization (HR 0.157; 95% CI 0.035-0.703, p=0.016). CONCLUSION: Elective PCI reduced major adverse events and was found to be an effective treatment modality in elderly patients with angina pectoris and significant coronary artery stenosis, compared to OMT. PMID- 26847291 TI - Deep Vein Thrombosis in the Lower Extremities in Comatose Elderly Patients with Acute Neurological Diseases. AB - PURPOSE: Comatose elderly patients with acute neurological illness have a great risk of deep vein thrombosis (DVT). In this study, the incidence of DVT and the effectiveness of early initiation of treatment were evaluated in those patients. MATERIALS AND METHODS: Total 323 patients were admitted to our ward due to neurological diseases in one year, and 43 patients, whose Glasgow Coma Scale was <= 11 and who was older than >= 60 years, were included in this study. D-dimer was measured on admission and day 7, and lower-extremity ultrasonography was performed on day 7. When DVT was positive, heparin treatment was initiated, and further evaluation of pulmonary embolism (PE) was conducted. Vena cava filter protection was inserted in PE-positive patients. Incidence of DVT and PE, alteration of D-dimer value, and effect of heparin treatment were analyzed. RESULTS: DVT was positive in 19 (44.2%) patients, and PE was in 4 (9.3%). D-dimer was significantly higher in DVT-positive group on day 7 (p<0.01). No DVT were identified in patients with ischemic disease, while 66.7% of intracerebral hemorrhage and 53.3% of brain contusion patients were DVT positive. Surgery was a definite risk factor for DVT, with an odds ratio of 5.25. DVT and PE disappeared by treatment in all cases, and no patients were succumbed to the thrombosis. CONCLUSION: Patients with hemorrhagic diseases or who undergo operation possess high risk of DVT, and initiation of heparin treatment in 7 days after admission is an effective prophylaxis for DVT in comatose elderly patients without causing bleeding. PMID- 26847292 TI - Retrospective Analysis on the Effects of House Dust Mite Specific Immunotherapy for More Than 3 Years in Atopic Dermatitis. AB - PURPOSE: In extrinsic atopic dermatitis (AD), house dust mites (HDM) play a role in eliciting or aggravating allergic lesions. The nature of skin inflammation in AD has raised a growing interest in allergen-specific immunotherapy (SIT). Thus, we assessed clinical improvement and laboratory parameters for evaluation of the benefit of long-term SIT. MATERIALS AND METHODS: A total of 217 AD patients who were treated with SIT for at least 3 years were retrospectively assessed, by using their investigator global assessment, pruritus scores, loss of sleep (LOS), total serum IgE, and eosinophil counts collected. Patients were additionally classified into subgroups according to age, initial AD severity and mono- or multi-sensitization to include different individual factors in the evaluation of SIT efficacy. Lastly, we compared laboratory data of good responders to SIT with that of poor responders to SIT. RESULTS: Improvement after SIT therapy was observed in 192 out of 217 patients (88.4%). Among these patients, 138 (63.5%) achieved excellent, near-complete or complete clinical remission. Significant reduction of pruritus, LOS, and the mean value of total serum IgE were observed (p<0.01). Better outcome was found in patients younger than 12 years of age (p=0.024). Patients with moderate to severe AD showed better treatment outcomes (p=0.036). Patients sensitized only to HDM had the better response to treatment, but SIT was also effective in multi-sensitized groups (p=1.051). No significant differences in baseline laboratory results were observed between good and poor responders (p>0.05). CONCLUSION: We emphasize the usefulness of long-term HDM SIT as a disease-modifying therapy for AD. PMID- 26847293 TI - Standardization of Weed Pollen Extracts, Japanese Hop and Mugwort, in Korea. AB - PURPOSE: Japanese hop (Humulus spp.) and mugwort (Artemisia spp.) are notable causes of autumn pollinosis in East Asia. However, Japanese hop and mugwort pollen extracts, which are widely used for the diagnosis, have not been standardized. This study was performed to standardize Japanese hop and mugwort pollen extracts. MATERIALS AND METHODS: Allergen extracts were prepared in a standardized way using locally collected Humulus japonicus and purchased Artemisia vulgaris pollens. The immunoglobulin E (IgE) reactivities of prepared extracts were compared with commercial extracts via IgE immunoblotting and inhibition analyses. Intradermal skin tests were performed to determine the bioequivalent allergy unit (BAU). RESULTS: The IgE reactive components of the extracts via IgE immunoblotting were similar to those of commercial extracts. A 11-kDa allergen showed the strongest IgE reactivity in Japanese hop, as did a 28 kDa allergen in mugwort pollen extracts. Allergenic potencies of the investigatory Japanese hop and mugwort extracts were essentially indistinguishable from the commercial ones. Sums of erythema of 50 mm by the intradermal skin test (SigmaED50) were calculated to be 14.4th and 13.6th three fold dilutions for Japanese hop and mugwort extracts, respectively. Therefore, the allergenic activity of the prepared extracts was 90827.4 BAU/mg for Japanese hop and 34412 BAU/mg for mugwort. CONCLUSION: We produced Japanese hop and mugwort pollen extracts using a standardized method. Standardized Japanese hop and mugwort pollen extracts will facilitate the production of improved diagnostic and immunotherapeutic reagents. PMID- 26847294 TI - Is Tamsulosin 0.2 mg Effective and Safe as a First-Line Treatment Compared with Other Alpha Blockers?: A Meta-Analysis and a Moderator Focused Study. AB - PURPOSE: Tamsulosin 0.2 mg is used widely in Asian people, but the low dose has been studied less than tamsulosin 0.4 mg or other alpha blockers of standard dose. This study investigated the efficacy and safety of tamsulosin 0.2 mg by a meta-analysis and meta-regression. MATERIALS AND METHODS: We conducted a meta analysis of efficacy of tamsulosin 0.2 mg using International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), post-voided residual volume (PVR), and quality of life (QoL). Safety was analyzed using adverse events. Relevant studies were searched using MEDLINE, EMBASE, and Cochrane library from January 1980 to June 2013. RESULTS: Ten studies were included with a total sample size of 1418 subjects [722 tamsulosin 0.2 mg group and 696 other alpha-blockers (terazosin, doxazosin, naftopidil, silodosin) group]. Study duration ranged from 4 to 24 weeks. The pooled overall standardized mean differences (SMD) in the mean change of IPSS from baseline for the tamsulosin group versus the control group was 0.02 [95% confidence interval (CI); -0.20, 0.25]. The pooled overall SMD in the mean change of QoL from baseline for the tamsulosin group versus the control group was 0.16 (95% CI; -0.16, 0.48). The regression analysis with the continuous variables (number of patients, study duration) revealed no significance in all outcomes as IPSS, QoL, and Qmax. CONCLUSION: This study clarifies that tamsulosin 0.2 mg has similar efficacy and fewer adverse events compared with other alpha blockers as an initial treatment strategy for men with lower urinary tract symptoms. PMID- 26847295 TI - The Epidemiology of Myasthenia Gravis in Korea. AB - PURPOSE: An epidemiological study of myasthenia gravis (MG) has not been performed in Korea. The purpose of this study was to estimate the prevalence and incidence of MG in Korea. MATERIALS AND METHODS: Health Insurance Review and Assessment (HIRA) data from 2010 to 2014 were searched for MG codes as defined by the International Classification of Diseases, 10th revision. After identifying MG cases, we estimated the prevalence and annual incidence of MG based on the HIRA database and Korean population data. RESULTS: During the study period, 10138 MG cases were identified. The prevalence of MG was 10.42 cases per 100000 people in 2010 and this increased every year to 12.99 cases per 100000 people in 2014. The average incidence of MG between 2011 and 2014 was 0.69 cases per 100000 person years. The prevalence and incidence were higher in the older (>= 50 years) age group than in the younger (<50 years) age group [prevalence: 9.26 vs. 19.24 per 100000, relative risk 2.077, 95% confidence interval (CI) 1.976-2.183, p<0.001; incidence: 0.47 vs. 1.18 per 100000, relative risk 2.490, 95% CI 2.006-3.091, p<0.001]. CONCLUSION: This study was the first nationwide population-based epidemiological study of MG in Korea. The prevalence and incidence of MG were consistent with those of previous studies. We found an increase in the prevalence of MG and a predominance of elderly MG patients. PMID- 26847296 TI - Possible Prevention of Neonatal Death: A Regional Population-Based Study in Japan. AB - PURPOSE: The neonatal mortality rate in Japan has currently been at the lowest level in the world. However, it is unclear whether there are still some potentially preventable neonatal deaths. We, therefore, aimed to examine the backgrounds of neonatal death and the possibilities of prevention in a region of Japan. MATERIALS AND METHODS: This is a population-based study of neonatal death in Shiga Prefecture of Japan. RESULTS: The 103 neonatal deaths in our prefecture between 2007 and 2011 were included. After reviewing by a peer-review team, we classified the backgrounds of these neonatal deaths and analyzed end-of-life care approaches associated with prenatal diagnosis. Furthermore, we evaluated the possibilities of preventable neonatal death, suggesting specific recommendations for its prevention. We analyzed 102 (99%) of the neonatal deaths. Congenital malformations and extreme prematurity were the first and the second most common causes of death, respectively. More than half of the congenital abnormalities (59%) including malformations and chromosome abnormality had been diagnosed before births. We had 22 neonates with non-intensive care including eighteen cases with congenital abnormality and four with extreme prematurity. Twenty three cases were judged to have had some possibility of prevention with one having had a strong possibility of prevention. Among specific recommendations of preventable neonatal death, more than half of them were for obstetricians. CONCLUSION: There is room to reduce neonatal deaths in Japan. Prevention of neonatal death requires grater prenatal care by obstetricians before birth rather than improved neonatal care by neonatologists after birth. PMID- 26847297 TI - Short-Term Analysis of Food Tolerance and Quality of Life after Laparoscopic Greater Curvature Plication. AB - PURPOSE: The aim of this study was to compare short-term outcomes [food tolerance scores (FTS) and quality of life] after three types of restrictive bariatric surgery: laparoscopic adjustable gastric banding (LAGB), laparoscopic greater curvature plication (LGCP), and laparoscopic sleeve gastrectomy (LSG). MATERIALS AND METHODS: From January 2012 to December 2013, all patients that underwent primary surgery were included in one of the LAGB, LGCP, or LSG groups. These three groups were then compared with respect to FTS, gastrointestinal quality of life indices (GIQLI), and the Medical Outcomes Study Short-Form 36 (SF-36) questionnaire. Questionnaires were sent to all patients both pre- and post operatively. RESULTS: A total of 85 patients (LAGB=45, LGCP=22, and LSG=18) returned the questionnaires in full, and these patients constituted the study cohort. The cohort was predominately female (n=73, 85.9%). Mean percentage excess weight loss (%EWL) values after LAGB, LGCP, and LSG were 65.4 +/- 27.0%, 65.6 +/- 25.2%, and 82.7 +/- 21.7%, respectively (p=0.044). Mean postoperative FTSs and improvements in total GIQLIs after LAGB, LGCP, and LSG were 15.96, 20.95, and 21.33 and -3.40, 6.68, and 18.78, respectively (p<0.05). All procedures produced improvements in the three SF-36 domain scores. Subgroup analysis revealed significant differences between the three procedures in terms of improvements in general health and emotional well-being. CONCLUSION: LGCP is safe and effective at achieving significant weight loss. In terms of food tolerance and GI quality of life, LGCP was found to be comparable to gastric banding and sleeve gastrectomy. PMID- 26847298 TI - Transplantation of a Scaffold-Free Cartilage Tissue Analogue for the Treatment of Physeal Cartilage Injury of the Proximal Tibia in Rabbits. AB - PURPOSE: The purpose of this study was to investigate the effects of transplantation of an in vitro-generated, scaffold-free, tissue-engineered cartilage tissue analogue (CTA) using a suspension chondrocyte culture in a rabbit growth-arrest model. MATERIALS AND METHODS: We harvested cartilage cells from the articular cartilage of the joints of white rabbits and made a CTA using a suspension culture of 2*107 cells/mL. An animal growth plate defect model was made on the medial side of the proximal tibial growth plate of both tibias of 6 week-old New Zealand white rabbits (n=10). The allogenic CTA was then transplanted onto the right proximal tibial defect. As a control, no implantation was performed on the left-side defect. Plain radiographs and the medial proximal tibial angle were obtained at 1-week intervals for evaluation of bone bridge formation and the degree of angular deformity until postoperative week 6. We performed a histological evaluation using hematoxylin-eosin and Alcian blue staining at postoperative weeks 4 and 6. RESULTS: Radiologic study revealed a median medial proximal tibial angle of 59.0 degrees in the control group and 80.0 degrees in the CTA group at 6 weeks. In the control group, statistically significant angular deformities were seen 3 weeks after transplantation (p<0.05). On histological examination, the transplanted CTA was maintained in the CTA group at 4 and 6 weeks postoperative. Bone bridge formation was observed in the control group. CONCLUSION: In this study, CTA transplantation minimized deformity in the rabbit growth plate injury model, probably via the attenuation of bone bridge formation. PMID- 26847299 TI - Validation of the Korean Version of the DN4 Diagnostic Questionnaire for Neuropathic Pain in Patients with Lumbar or Lumbar-Radicular Pain. AB - PURPOSE: To evaluate the diagnostic value of the Korean version of the Douleur Neuropathique 4 (DN4) questionnaire and to validate this questionnaire in terms of psychometric properties in patients with chronic pain due to degenerative spinal disease. MATERIALS AND METHODS: The Korean version of the DN4 questionnaire, which was translated and linguistically validated by the MAPI Research Group, was tested on 83 patients with lumbar or lumbar-radicular pain. Test-retest reliability was evaluated in a subsample of 40 patients who completed two assessments with an interval of 2 weeks. Nociceptive pain and neuropathic component pain were diagnosed in 40 and 43 patients, respectively. RESULTS: The Cronbach's alpha coefficient of internal consistency was 0.819, and the test retest intraclass correlation coefficient (3, 1) (95% confidence interval) was 0.813 (0.776-0.847) (n=40). The area under the receiver-operator characteristics curve was 0.953 (p<0.001), with 95% confidence interval between 0.869 and 0.990. The Korean version of the DN4 questionnaire showed a sensitivity of 100% and 87.1%, and a specificity of 88.2% and 94.1% at the cutoff value of 3/10 and 4/10, respectively, for discriminating neuropathic component pain. CONCLUSION: The present study demonstrated the good discriminatory power of DN4 between nociceptive pain and neuropathic component pain in patients with lumbar or lumbar radicular pain. PMID- 26847300 TI - Factors Influencing Outcomes after Ulnar Nerve Stability-Based Surgery for Cubital Tunnel Syndrome: A Prospective Cohort Study. AB - PURPOSE: Simple decompression of the ulnar nerve has outcomes similar to anterior transposition for cubital tunnel syndrome; however, there is no consensus on the proper technique for patients with an unstable ulnar nerve. We hypothesized that 1) simple decompression or anterior ulnar nerve transposition, depending on nerve stability, would be effective for cubital tunnel syndrome and that 2) there would be determining factors of the clinical outcome at two years. MATERIALS AND METHODS: Forty-one patients with cubital tunnel syndrome underwent simple decompression (n=30) or anterior transposition (n=11) according to an assessment of intra-operative ulnar nerve stability. Clinical outcome was assessed using grip and pinch strength, two-point discrimination, the mean of the disabilities of arm, shoulder, and hand (DASH) survey, and the modified Bishop Scale. RESULTS: Preoperatively, two patients were rated as mild, another 20 as moderate, and the remaining 19 as severe according to the Dellon Scale. At 2 years after operation, mean grip/pinch strength increased significantly from 19.4/3.2 kg to 31.1/4.1 kg, respectively. Two-point discrimination improved from 6.0 mm to 3.2 mm. The DASH score improved from 31.0 to 14.5. All but one patient scored good or excellent according to the modified Bishop Scale. Correlations were found between the DASH score at two years and age, pre-operative grip strength, and two-point discrimination. CONCLUSION: An ulnar nerve stability-based approach to surgery selection for cubital tunnel syndrome was effective based on 2-year follow-up data. Older age, worse preoperative grip strength, and worse two-point discrimination were associated with worse outcomes at 2 years. PMID- 26847301 TI - Non-Invasive Prediction of Histologic Chorioamnionitis in Women with Preterm Premature Rupture of Membranes. AB - PURPOSE: To develop a model based on non-invasive clinical and ultrasonographic parameters for predicting the likelihood of subsequent histologic chorioamnionitis in women with preterm premature rupture of membranes (PPROM) and to determine whether the inclusion of invasive test results improves the predictive value of the model. MATERIALS AND METHODS: This retrospective cohort study included 146 consecutive women presenting with PPROM (20-33 weeks). Transvaginal ultrasonographic assessment of cervical length was performed. Maternal serum C-reactive protein (CRP) levels and white blood cell (WBC) counts were measured after amniocentesis. Amniotic fluid (AF) obtained by amniocentesis was cultured, and interleukin-6 (IL-6) levels and WBC counts were determined. The primary outcome measure was histologic chorioamnionitis. RESULTS: Risk scores based on serum CRP concentrations and gestational age (model 1) were calculated for each patient. The model was shown to have adequate goodness of fit and an area under the receiver operating characteristic curve (AUC) of 0.742. When including AF test results (e.g., AF IL-6 levels) in model 1, serum CRP concentrations were found to be insignificant, and thus, were excluded from model 2, comprising AF IL-6 levels and gestational age. No significant difference in AUC was found between models 1 and 2. CONCLUSION: For women with PPROM, the newly developed model incorporating non-invasive parameters (serum CRP and gestational age) was moderately predictive of histologic chorioamnionitis. The inclusion of invasive test results added no predictive information to the model in this setting. PMID- 26847302 TI - Expression of CAIII and Hsp70 Is Increased the Mucous Membrane of the Posterior Commissure in Laryngopharyngeal Reflux Disease. AB - PURPOSE: We tried to evaluate the difference in the expression of carbonic anhydrase (CA) III and heat shock protein (Hsp) 70 between laryngopharyngeal reflux disease (LPRD) and non-LPRD patients. MATERIALS AND METHODS: The study involved 28 patients who underwent laryngeal microsurgery due to benign laryngeal disease from March to August 2008. Reflux symptom index (RSI) and reflux finding score (RFS) were measured for each person, and they were assigned either to the LPRD group (n=10) or non-LPRD group (n=18). Tissue samples were obtained from the mucosa of posterior commissure, and immunohistochemistry (IHC) staining of CAIII and Hsp70 was performed. The IHC scores were measured and compared with clinical features including RSI and RFS. RESULTS: Total 10 patients were assigned as LPRD group, and 18 patients were as control group. The mean IHC score of CAIII and Hsp70 was 1.70 +/- 1.06 and 1.90 +/- 0.88, respectively, in LPRD patients, whereas the mean IHC score of CAIII and Hsp70 was 0.78 +/- 0.73 and 0.94 +/- 0.87, respectively, in non-LPRD patients. The difference between two groups was statistically significant (p<0.05). CONCLUSION: CAIII and Hsp70 expressions were higher in LPRD patients that in non-LPRD patients, suggesting the possibility as one of biomomarker in LPRD diagnosis. PMID- 26847303 TI - Intrathecal Morphine Infusion Therapy in Management of Chronic Pain: Present and Future Implementation in Korea. AB - PURPOSE: Intrathecal morphine pump (ITMP) infusion therapy is efficient in managing malignant and nonmalignant chronic pain refractory to standard treatment. However, the high cost of an ITMP is the greatest barrier for starting a patient on ITMP infusion therapy. Using the revised Korean reimbursement guidelines, we investigated the cost effectiveness of ITMP infusion therapy and conducted a patient survey. MATERIALS AND METHODS: A retrospective chart review of 12 patients who underwent ITMP implantation was performed. Morphine dose escalation rates were calculated, and numeric rating scale (NRS) scores were compared before and after ITMP implantation. We surveyed patients who were already using an ITMP as well as those who were candidates for an ITMP. All survey data were collected through in-person interviews over 3 months. Data on the cost of medical treatment were collected and projected over time. RESULTS: The NRS score decreased during the follow-up period. The median morphine dose increased by 36.9% over the first year, and the median time required to reach a financial break-even point was 24.2 months. Patients were more satisfied with the efficacy of ITMP infusion therapy than with conventional therapy. The expected cost of ITMP implantation was KRW 4000000-5000000 in more than half of ITMP candidates scheduled to undergo implantation. CONCLUSION: The high cost of initiating ITMP infusion therapy is challenging; however, the present results may encourage more patients to consider ITMP therapy. PMID- 26847305 TI - Comparison between Steroid Injection and Stretching Exercise on the Scalene of Patients with Upper Extremity Paresthesia: Randomized Cross-Over Study. AB - PURPOSE: To compare the therapeutic effects on upper extremity paresthesia of intra-muscular steroid injections into the scalene muscle with those of stretching exercise only. MATERIALS AND METHODS: Twenty patients with upper extremity paresthesia who met the criteria were recruited to participate in this single-blind, crossover study. Fourteen of 20 patients were female. The average age was 45.0 +/- 10.5 years and duration of symptom was 12.2 +/- 8.7 months. Each participant completed one injection and daily exercise program for 2 weeks. After randomization, half of all patients received ultrasound-guided injection of scalene muscles before exercise, while the other was invested for the other patients. RESULTS: After two weeks, there was a significant decrease of the visual analog scale score of treatment effect compared with baseline in both groups (6.90 to 2.85 after injection and 5.65 to 4.05 after stretching exercise, p<0.01). However, injection resulted in greater improvements than stretching exercise (p<0.01). The number of patients with successful treatment, defined as >50% reduction in post-treatment visual analog scale, was 18 of 20 (90.0%) after injection, compared to 5 of 20 (25.0%) after stretching exercise. There were no cases of unintended brachial plexus block after injection. CONCLUSION: Ultrasound guided steroid injection or stretching exercise of scalene muscles led to reduced upper extremity paresthesia in patients who present with localized tenderness in the scalene muscle without electrodiagnostic test abnormalities, although injection treatment resulted in more improvements. The results suggest that symptoms relief might result from injection into the muscle alone not related to blockade of the brachial plexus. PMID- 26847304 TI - Expression of Autophagy and Reactive Oxygen Species-Related Proteins in Lacrimal Gland Adenoid Cystic Carcinoma. AB - PURPOSE: To investigate the difference of expression of autophagy and reactive oxygen species (ROS) related proteins in adenoid cystic carcinoma (ACC) of lacrimal gland in comparison with ACC of salivary gland. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue samples from patients pathologically diagnosed as lacrimal gland ACC (n=11) and salivary gland ACC (n=64) were used. Immunochemistry was used to measure expression of autophagy related proteins [beclin-1, light chain (LC) 3A, LC3B, p62, and BCL2/adenovirus E1B 19 kDa protein interacting protein 3 (BNIP3)] and ROS related proteins [catalase, thioredoxinreductase, glutathione S-transferasepi (GSTpi), thioredoxin interacting protein, and manganese superoxide dismutase (MnSOD)]. The prognostic factors related to disease-free and overall survival (OS) in lacrimal gland ACC by log-rank tests, were determined. RESULTS: GSTpi in stromal cells was more highly expressed in lacrimal gland ACC (p=0.006), however, MnSOD in epithelial cells was expressed more in salivary gland ACC (p=0.046). LC3B positivity and BNIP3 positivity in epithelial component were associated with shorter disease free survival (both p=0.002), and LC3A positivity in stromal component was the factor related to shorter OS (p=0.005). CONCLUSION: This is the first study to demonstrate the expression of autophagy and ROS related proteins in lacrimal gland ACC in comparison with the salivary gland ACC, which would provide a basis for further study of autophagy and ROS mechanism as novel therapeutic targets in lacrimal gland ACC. PMID- 26847306 TI - Botulinum Toxin Type A Injection for Spastic Equinovarus Foot in Children with Spastic Cerebral Palsy: Effects on Gait and Foot Pressure Distribution. AB - PURPOSE: To investigate the effect of intramuscular Botulinum toxin type A (BoNT A) injection on gait and dynamic foot pressure distribution in children with spastic cerebral palsy (CP) with dynamic equinovarus foot. MATERIALS AND METHODS: Twenty-five legs of 25 children with CP were investigated in this study. BoNT-A was injected into the gastrocnemius (GCM) and tibialis posterior (TP) muscles under the guidance of ultrasonography. The effects of the toxin were clinically assessed using the modified Ashworth scale (MAS) and modified Tardieu scale (MTS), and a computerized gait analysis and dynamic foot pressure measurements using the F-scan system were also performed before injection and at 1 and 4 months after injection. RESULTS: Spasticity of the ankle plantar-flexor in both the MAS and MTS was significantly reduced at both 1 and 4 months after injection. On dynamic foot pressure measurements, the center of pressure index and coronal index, which represent the asymmetrical weight-bearing of the medial and lateral columns of the foot, significantly improved at both 1 and 4 months after injection. The dynamic foot pressure index, total contact area, contact length and hind foot contact width all increased at 1 month after injection, suggesting better heel contact. Ankle kinematic data were significantly improved at both 1 and 4 months after injection, and ankle power generation was significantly increased at 4 months after injection compared to baseline data. CONCLUSION: Using a computerized gait analysis and foot scan, this study revealed significant benefits of BoNT-A injection into the GCM and TP muscles for dynamic equinovarus foot in children with spastic CP. PMID- 26847307 TI - Training a Chest Compression of 6-7 cm Depth for High Quality Cardiopulmonary Resuscitation in Hospital Setting: A Randomised Controlled Trial. AB - PURPOSE: During cardiopulmonary resuscitation (CPR), chest compression (CC) depth is influenced by the surface on which the patient is placed. We hypothesized that training healthcare providers to perform a CC depth of 6-7 cm (instead of 5-6 cm) on a manikin placed on a mattress during CPR in the hospital might improve their proper CC depth. MATERIALS AND METHODS: This prospective randomised controlled study involved 66 premedical students without CPR training. The control group was trained to use a CC depth of 5-6 cm (G 5-6), while the experimental group was taught to use a CC depth of 6-7 cm (G 6-7) with a manikin on the floor. All participants performed CCs for 2 min on a manikin that was placed on a bed 1 hour and then again 4 weeks after the training without a feedback. The parameters of CC quality (depth, rate, % of accurate depth) were assessed and compared between the 2 groups. RESULTS: Four students were excluded due to loss to follow-up and recording errors, and data of 62 were analysed. CC depth and % of accurate depth were significantly higher among students in the G 6-7 than G 5-6 both 1 hour and 4 weeks after the training (p<0.001), whereas CC rate was not different between two groups (p>0.05). CONCLUSION: Training healthcare providers to perform a CC depth of 6-7 cm could improve quality CC depth when performing CCs on patients who are placed on a mattress during CPR in a hospital setting. PMID- 26847308 TI - Adverse Cardiovascular Events after a Venomous Snakebite in Korea. AB - PURPOSE: Although cardiac involvement is an infrequently recognized manifestation of venomous snakebites, little is known of the adverse cardiovascular events (ACVEs) arising as a result of snakebite in Korea. Accordingly, we studied the prevalence of ACVEs associated with venomous snakebites in Korea and compared the clinical features of patients with and without ACVEs. MATERIALS AND METHODS: A retrospective review was conducted on 65 consecutive venomous snakebite cases diagnosed and treated at the emergency department of Wonju Severance Christian Hospital between May 2011 and October 2014. ACVEs were defined as the occurrence of at least one of the following: 1) myocardial injury, 2) shock, 3) ventricular dysrhythmia, or 4) cardiac arrest. RESULTS: Nine (13.8%) of the 65 patients had ACVEs; myocardial injury (9 patients, 13.8%) included high sensitivity troponin I (hs-TnI) elevation (7 patients, 10.8%) or electrocardiogram (ECG) determined ischemic change (2 patients, 3.1%), and shock (2 patient, 3.1%). Neither ventricular dysrhythmia nor cardiac arrest was observed. The median of elevated hs-TnI levels observed in the present study were 0.063 ng/mL (maximum: 3.000 ng/mL) and there was no mortality in the ACVEs group. Underlying cardiac diseases were more common in the ACVEs group than in the non-ACVEs group (p=0.017). Regarding complications during hospitalization, 3 patients (5.4%) in the non ACVEs group and 3 patients (33.3%) in the ACVEs group developed bleeding (p=0.031). CONCLUSION: Significant proportion of the patients with venomous snakebite is associated with occurrence of ACVEs. Patients with ACVEs had more underlying cardiac disease and bleeding complication. PMID- 26847309 TI - Surgical Treatment of Hemangioblastoma in the Pituitary Stalk: An Extremely Rare Case. AB - Hemangioblastoma (HBL) in the pituitary stalk is extremely rare. Only 16 such cases have been reported in the past and 5 cases have been treated with surgical procedure. Here, we report surgical case of HBL in the pituitary stalk diagnosed in a 34-year-old woman. The patient underwent a gross-total resection via the modified lateral supra-orbital approach. No recurrence was observed in two years after surgery. To our knowledge, this is the 17th case of HBL in the pituitary stalk and the 6th surgical case. If the tumor is symptomatic and the volume is over 5 cubic centimeters as in our case, we recommend that the surgical resection of the HBL in the pituitary stalk is a more safe and reasonable than radiotherapy. PMID- 26847310 TI - A Rare Case of Intra-Endometrial Leiomyoma of Uterus Simulating Degenerated Submucosal Leiomyoma Accompanied by a Large Sertoli-Leydig Cell Tumor. AB - A 50-year-old peri-menopausal woman presented with hard palpable mass on her lower abdomen and anemia from heavy menstrual bleeding. Ultrasonography showed a 13*12 cm sized hypoechoic solid mass in pelvis and a 2.5*2 cm hypoechoic cystic mass in uterine endometrium. Abdomino-pelvic computed tomography revealed a hypodense pelvic mass without enhancement, suggesting a leiomyoma of intraligamentary type or sex cord tumor of right ovary with submucosal myoma of uterus. Laparoscopy revealed a large Sertoli-Leydig cell tumor of right ovary with a very rare entity of intra-endometrial uterine leiomyoma accompanied by adenomyosis. The final diagnosis of ovarian sex-cord tumor (Sertoli-Leydig cell), stage Ia with intra-endometrial leiomyoma with adenomyosis, was made. Considering the large size of the tumor and poorly differentiated nature, 6 cycles of chemotherapy with Taxol and Carboplatin regimen were administered. There is neither evidence of major complications nor recurrence during 20 months' follow up. PMID- 26847312 TI - A Case of Dasatinib-Induced Nephrotic Syndrome in a Child with Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia. PMID- 26847313 TI - Application of Ventilating-Bronchoscopy-Adaptor by Fusing a Laparoscopic Trocar during Bronchial Thermoplasty under General Anesthesia. PMID- 26847311 TI - Non-Paraneoplastic Autoimmune Retinopathy: The First Case Report in Korea. AB - Autoimmune retinopathy (AIR) is an immune-mediated retinopathy, resulting from an immunologic process caused by the aberrant recognition of retinal antigens as autoantigens. The diagnosis of AIR involves the detection of antiretinal antibodies with concurrent clinical and electrophysiological evidence of retinopathy. A 40-year-old patient presented with progressive loss of bilateral vision over several months. A fundus examination was unremarkable. Spectral domain optical coherence tomography revealed a blurred photoreceptor ellipsoid zone at the subfoveal region in both eyes with more prominent disruption in the left eye. Full-field electroretinography (ERG) showed relatively normal rod and cone responses in the right eye, and decreased photopic bwaves with minimal attenuation of a-waves in the left eye. Multifocal ERG demonstrated slightly reduced amplitude of the inner segment ring in the right eye and decreased amplitudes and delayed latencies of all modalities in the left eye. The patient was suspected to have AIR and it was supported by positive Western blots for 23 kDa protein, enolase (46-kDa), aldolase (40-kDa), 62-kDa and 78-kDa proteins and by immunohistochemical staining of human retinal bipolar and ganglion cells. Despite the immunosuppressive treatment, the destruction of the retinal photoreceptors progressed, and immunosuppressive interventions produced very little visual improvement. We report on what is, to the best of our knowledge, the very first case of serologically confirmed nonparaneoplastic AIR in Korea. PMID- 26847314 TI - Successful Application of Veno-Venoarterial Extracorporeal Membrane Oxygenation for Acute Exacerbation of Asthma Followed by Stress Cardiomyopathy. PMID- 26847315 TI - Ultrasound-Guided Trigger Point Injection for Myofascial Trigger Points in the Subscapularis and Pectoralis Muscles. PMID- 26847316 TI - Sex and gender in hand therapy research. PMID- 26847317 TI - Clinical Relevance Commentary on: Hand therapy versus corticosteroid injections in the treatment of de Quervain's disease: A systematic review and meta-analysis. PMID- 26847318 TI - Integration of occupation based intervention in hand injury rehabilitation: A Randomized Controlled Trial. AB - STUDY DESIGN: Randomized Controlled Trial (RCT). INTRODUCTION: Engagement in daily occupations and day to day activities helps to restore function in individuals with injured hands and provides a platform to practise selected occupations. PURPOSE: The purpose of this study was to investigate the effectiveness of a combination of Occupation Based Intervention (OBI) and Therapeutic Exercise (TE) compared to TE alone for the rehabilitation of hand injuries. METHOD: A single center RCT, parallel group was conducted at the Kuala Lumpur General Hospital (KLGH), Malaysia. Forty-six adult clients with hand injuries who consented to participate were randomly allocated to either the OBI + TE group or to the TE group. RESULTS: Following a ten week intervention program, statistical significance differences were found in DASH score (TE = 18.64 +/- 14.84 vs OBI + TE = 9.50 +/- 9.14, p = 0.02); total active motion (TE = 1035.85 +/- 179.84 vs OBI + TE = 1203.65 +/- 133.60, p = 0.01); neuropathic pain (TE = 2.90 +/- 2.79 vs OBI + TE = 1.05 +/- 2.01, p = 0.02); COPM performance (TE = 7.62 +/- 2.03 vs OBI + TE = 9.53 +/- 0.64, p < 0.001); and COPM satisfaction (TE = 7.60 +/- 2.11 vs OBI + TE = 9.49 +/- 0.76, p < 0.001) in favor of OBI + TE group. CONCLUSION: This study highlighted the integration of OBI into hand injury rehabilitation improved outcomes for clients. PMID- 26847319 TI - Effects of serial casting in the treatment of flexion contractures of proximal interphalangeal joints in patients with rheumatoid arthritis and juvenile idiopathic arthritis: A retrospective study. AB - AIM: To analyze the effects of serial casting (SC) in the treatment of proximal interphalangeal (PIP) joint flexion contractures in patients with rheumatoid arthritis and juvenile idiopathic arthritis. STUDY DESIGN: Retrospective case series. METHODS: The data of 18 patients treated with SC were obtained from their patient records. The angular changes in the finger joints were analyzed and compared statistically using t-tests. RESULTS: A total of 49 fingers were serially casted with plaster of Paris over a 14-year period. The SC resulted in significant (26.8 degrees ; p < 0.001) reduction in the PIP joint extension loss. Small, but statistically significant, losses in flexion were associated with these gains. (p < 0.001). Angular changes were also observed in the other finger joints. The magnitude of the initial extension loss was the only factor to explain the amount of motion gained (p < 0.001; R2 = 0.38). CONCLUSION: SC is an effective method to correct flexion contractures in PIP joints in selected patients with arthritis. The gain is partially related to the magnitude of initial extension loss. PMID- 26847320 TI - Robot training for hand motor recovery in subacute stroke patients: A randomized controlled trial. AB - BACKGROUND: Evidence of superiority of robot training for the hand over classical therapies in stroke patients remains controversial. During the subacute stage, hand training is likely to be the most useful. AIM: To establish whether robot active assisted therapies provides any additional motor recovery for the hand when administered during the subacute stage (<4 months from event) in a Mexican adult population diagnosed with stroke. HYPOTHESIS: Compared to classical occupational therapy, robot based therapies for hand recovery will show significant differences at subacute stages. TRIAL DESIGN: A randomized clinical trial. METHODS: A between subjects randomized controlled trial was carried out on subacute stroke patients (n = 17) comparing robot active assisted therapy (RT) with a classical occupational therapy (OT). Both groups received 40 sessions ensuring at least 300 repetitions per session. Treatment duration was (mean +/- std) 2.18 +/- 1.25 months for the control group and 2.44 +/- 0.88 months for the study group. The primary outcome was motor dexterity changes assessed with the Fugl-Meyer (FMA) and the Motricity Index (MI). RESULTS: Both groups (OT: n = 8; RT: n = 9) exhibited significant improvements over time (Non-parametric Cliff's delta-within effect sizes: dwOT-FMA = 0.5, dwOT-MI = 0.5, dwRT-FMA = 1, dwRT-MI = 1). Regarding differences between the therapies; the Fugl-Meyer score indicated a significant advantage for the hand training with the robot (FMA hand: WRS: W = 8, p <0.01), whilst the Motricity index suggested a greater improvement (size effect) in hand prehension for RT with respect to OT but failed to reach significance (MI prehension: W = 17.5, p = 0.080). No harm occurred. CONCLUSIONS: Robotic therapies may be useful during the subacute stages of stroke - both endpoints (FM hand and MI prehension) showed the expected trend with bigger effect size for the robotic intervention. Additional benefit of the robotic therapy over the control therapy was only significant when the difference was measured with FM, demanding further investigation with larger samples. Implications of this study are important for decision making during therapy administration and resource allocation. PMID- 26847322 TI - Evaluation of muscle strength and manual dexterity in patients with Charcot-Marie Tooth disease. AB - STUDY DESIGN: Matched pair study. INTRODUCTION: Differences in hand-muscle strength/dexterity between dominant (DH) and non-dominant (NDH) hand in Charcot Marie-Tooth disease (CMT) are not well understood. PURPOSE OF THE STUDY: To compare muscle strength/dexterity between DH and NDH and to correlate manual dexterity, strength and sensory function. PATIENTS AND METHODS: Thirty CMT patients were studied using functional muscle testing (FMT) and strength (dynamometry), dexterity (the Nine Hole Peg Test [NHPT]), and Jebsen-Taylor Hand Function [JTT]), and sensory function (the Nottingham Sensory Assessment [NSA]). RESULTS: Scores were worse for DH than NDH on FMT (p = 0.043) and NHPT (p = 0.014) but not on JTT (p = 0.098), handgrip strength (p = 0.710) or tripod pinch (p = 0.645). NSA did not correlate significantly with any tests (p's0.05). CONCLUSIONS: In CMT disease, DH appears more impaired than NDH in terms of function and dexterity. Greater muscle weakness in DH may also emerge as CMT progresses. LEVEL OF EVIDENCE: 3b. PMID- 26847321 TI - Influence of upper limb disability, manual dexterity and fine motor skill on general self-efficacy in institutionalized elderly with osteoarthritis. AB - STUDY DESIGN: Descriptive, cross-sectional. INTRODUCTION: The impact of upper limb (UL) disability, dexterity and fine motor skill on self-efficacy in older adults with osteoarthritis (OA) is not well known yet. PURPOSES OF THE STUDY: To evaluate the self-efficacy and its relationship with UL function/disability in institutionalized OA. METHODS: Institutionalized adults (n = 45) over the age of 65 years with OA were evaluated in a single session, to determine pinch strength, active range of motion of the hand and UL disability and functionality. They were classified as self-efficacious or not based on their general self-efficacy level. The influence on self-efficacy on upper limb function was statistically analyzed using bivariate and multivariate regression analyses. RESULTS: Self-effective older adults showed significantly lower scores in disability and higher scores in pinch strength, dexterity and motion of thumb than those who were classified as non-self-effective. Self-efficacy was associated with pinch strength (p <= 0.038), disability (p < 0.001) and dexterity (p <= 0.048). Multiple regression analyses showed that disability explained almost 40% of the variability of self efficacy. CONCLUSIONS: Older adults classified as non-self-effective have higher UL disability and less pinch strength, manual dexterity and thumb motion than those who are self-effective, suggesting a relationship between impairment and perceived ability. PMID- 26847323 TI - A comparison of electronic and manual dynamometry and goniometry in patients with fracture of the distal radius and healthy participants. AB - The purpose of this study was to assess the intra-rater and inter-rater reliability of electronic and manual dynamometry and goniometry in healthy volunteers, and the inter-instrument reliability in the assessment of healthy volunteers and patients recovering after a fracture of the distal radius. Grip strength, grip fatigue, pinch strength and range of motion were assessed in all participants with both the manual and electronic instruments by two physiotherapists and orthopaedic specialist trainee. The measures of dynamometry demonstrated excellent reliability (intra-class correlation coefficient >0.90), with the instruments found to be interchangeable with the exception of the grip fatigue. Variable intra-rater and inter-rater reliability was demonstrated with all planes of movement for the goniometry measures regardless of the instrument used. The results of this study support the continued use of dynamometry in the clinical setting, but raise questions regarding the use of goniometry measurements. LEVEL OF EVIDENCE: Diagnostic level III. PMID- 26847324 TI - Joint trajectories of internalizing and externalizing problems in preschool children with autism spectrum disorder. AB - The co-occurring development of internalizing and externalizing problems were examined in an inception cohort of 392 children diagnosed with autism spectrum disorder at age 3 who were assessed on four occasions. Results indicated that internalizing and externalizing problems were stable over time and highly comorbid. Joint trajectory analysis suggested that 13% of the sample followed a dual high-risk trajectory. High risk was not found to be associated with intellectual ability or autism spectrum disorder symptom severity but was linked to lower income and gender: more girls than boys were found in the high/stable internalizing problems trajectory. The results suggest that 1 in 4 preschoolers followed a trajectory of internalizing or externalizing problems (or a combination of the two) that could be characterized as clinically elevated. PMID- 26847326 TI - Ruthenium-Catalyzed Intermolecular Direct Silylation of Unreactive C(sp(3))-H Bonds. AB - A Ru-catalyzed intermolecular silylation of unreactive, aliphatic C(sp(3))-H bonds has been described for the first time. This protocol features low catalyst loading, a relatively broad substrate spectrum, good functional group tolerance, and no sensitivity to air, which provides a convenient and practical pathway for the construction of C-Si bonds. PMID- 26847325 TI - Money, Peers and Parents: Social and Economic Aspects of Inequality in Youth Wellbeing. AB - Indicators of social and economic status are important health determinants. However, evidence for the influence of family socioeconomic status in adolescent wellbeing is inconsistent and during this period of development youth may begin to develop their own status positions. This study examined social and economic health inequalities by applying a multidimensional and youth-orientated approach. Using a recent (2010-2011) and representative sample of Swedish 14-year olds (n = 4456, 51 % females), the impact of family socioeconomic status, youth economic resources and peer status on internalizing symptoms and self-rated health were examined. Data was based on population register, sociometric and self-report information. Aspects of family socioeconomic status, youth's own economy and peer status each showed independent associations, with poorer wellbeing observed with lower status. However, there were equally strong or even stronger effects of peer status and youth's own economy than family socioeconomic status. Lower household income and occupational status were more predictive of poor self-rated health than of internalizing symptoms. The findings suggest that youth's own economy and peer status are as important as family socioeconomic status for understanding inequalities in wellbeing. Thus, a focus on youth-orientated conceptualizations of social and economic disadvantage during adolescence is warranted. PMID- 26847327 TI - Physician Identification and Patient Satisfaction: Are They Related? PMID- 26847328 TI - In Comparing Diagnostic Accuracy of Ultrasound and Hepatobiliary Scintigraphy for Acute Cholecystitis, It Is Only Fair that Both Tests Are Done and Interpreted at a Comparable Skill Level. PMID- 26847329 TI - Somatic Mosaic Mutations in PPM1D and TP53 in the Blood of Women With Ovarian Carcinoma. AB - IMPORTANCE: Somatic mosaic mutations in PPM1D have been reported in patients with breast cancer, lung cancer, and ovarian cancer (OC), but cause or effect has not been established. OBSERVATIONS: To test the hypothesis that somatic mosaic mutations are associated with chemotherapy exposure, we used massively parallel sequencing to quantitate mutations in peripheral blood mononuclear cells (PBMCs) of 686 women with primary OC (n = 412) or relapsed OC (n = 274). The frequency of somatic mosaic PPM1D mutations in PBMCs was significantly associated with prior chemotherapy (P < .001), and, in patients exposed to chemotherapy, with older age at blood draw (recurrent OC odds ratio [OR], 17.24; 95% CI, 6.80-43.69; and primary OC postchemotherapy OR, 4.82; 95% CI, 1.43-16.18). In contrast, somatic mosaic mutations in TP53 were not significantly associated with chemotherapy or age. In sequential PBMC samples harvested from 13 patients with OC near diagnosis and after a median of 2 different chemotherapy regimens, somatic mosaic PPM1D mutations increased in 11 individuals (84.6%) and TP53 mutations appeared in 2 (15.4%). CONCLUSIONS AND RELEVANCE: Chemotherapy exposure and age influence the accumulation of PPM1D-mutated PBMC clones. Care should be taken to control for chemotherapy exposure and age at blood draw when testing the association of somatic mosaic mutations in PBMCs with cancer risk. PMID- 26847330 TI - Risk of acute kidney injury associated with neuroimaging obtained during triage and treatment of patients with acute ischemic stroke symptoms. AB - BACKGROUND: Combining non-contrast CT (NCCT), CT angiography (CTA), and CT perfusion (CTP) imaging (referred to as a CT stroke study, CTSS) provides a rapid evaluation of the cerebrovascular axis during acute ischemic stroke. Iodinated contrast-enhanced CT imaging is not without risk, which includes renal injury. If a patient's CTSS identifies vascular pathology, digital subtraction angiography (DSA) is often performed within 24-48 h. Such patients may receive multiple administrations of iodinated contrast material over a short time period. OBJECTIVE: We aimed to evaluate the incidence of acute kidney injury (AKI) in patients who underwent a CTSS and DSA for evaluation of acute ischemic symptoms or for stroke intervention within a 48 h period between August 2012 and December 2014. METHODS: We identified 84 patients for inclusion in the analysis. Patients fell into one of two cohorts: AKI, defined as a rise in the serum creatinine level of >=0.5 mg/dL from baseline, or non-AKI. Clinical parameters included pre- and post-imaging serum creatinine level, time between CTSS and DSA, and type of angiographic procedure (diagnostic vs intervention) performed. RESULTS: Four patients (4.7%) experienced AKI, one of whom had baseline renal dysfunction (defined as baseline serum creatinine level >=1.5 mg/dL). The mean difference between baseline and peak creatinine values was found to be significantly greater in patients with AKI than in non-AKI patients (1.65 vs -0.09, respectively; p=0.0008). CONCLUSIONS: This study provides preliminary evidence of the safety and feasibility of obtaining CTSS with additional DSA imaging, whether for diagnosis or intervention, to identify possible acute ischemic stroke. PMID- 26847331 TI - LVIS Jr 'shelf' technique: an alternative to Y stent-assisted aneurysm coiling. AB - Wide-necked bifurcation intracranial aneurysms have traditionally not been amenable to coil embolization with the use of a single stent due to the high risk of coil prolapse. Y-configuration double stent-assisted coil embolization ('Y stenting') of this aneurysm type has been shown to have generally good clinical outcomes, although the technique is complex with various challenges described in the literature. The compliant and flexible closed-cell design of braided stents such as the LVIS Jr allows for the creation of a 'shelf' across the aneurysm neck sufficient to prevent coil prolapse. We describe this novel 'shelf' technique and present a small case series of LVIS Jr stent-assisted wide-necked bifurcation intracranial aneurysm coiling in eight patients. Our small, albeit important, case series demonstrates that the 'shelf' technique is feasible and safe with very good short-term clinical and angiographic outcomes, and may obviate the need for Y-stenting. PMID- 26847332 TI - Could we clinicians be the greatest barrier to real progress in our field? PMID- 26847333 TI - Cerebral vasospasm and delayed cerebral infarctions in 225 patients with non aneurysmal subarachnoid hemorrhage: the underestimated risk of Fisher 3 blood distribution. AB - OBJECTIVE: Recent data have shown increasing numbers of non-aneurysmal subarachnoid hemorrhage (NASAH). However, data are limited and often only small series have been published. Our objective was to analyze the rate of cerebral vasospasm (CVS), delayed cerebral infarction (DCI), and their influence on the clinical outcome, especially in patients with diffuse Fisher 3 bleeding pattern NASAH (Fi3). METHODS: Between 1999 and 2014, 225 patients had NASAH. CVS, DCI, and outcome (according to the modified Rankin Scale at 6 months) were analyzed retrospectively. Patients were stratified according to the bleeding type. After univariate analysis a multivariate analysis was performed and NASAH Fi3 was also compared with aneurysmal SAH Fi3. RESULTS: Patient characteristics and the outcome of perimesencephalic (PM) and non-PM (NPM) SAH were similar. Excluding Fi3, PM and NPM without Fi3 had similar patient characteristics, clinical course, and outcome. In particular, the Fi3 subgroup had a significantly increased risk of CVS, DCI, unfavorable outcome, hydrocephalus, and death. Early hydrocephalus was associated with Fi3 and intraventricular hemorrhage. The multivariate regression model showed the variables elderly patients, Fi3, and early hydrocephalus as independent and significant predictors for an unfavorable outcome. A further comparison of NASAH Fi3 with aneurysmal SAH Fi3 showed similar characteristics, CVS rate, and mortality. CONCLUSIONS: Patients with NASAH without a Fi3 bleeding pattern had a similar excellent outcome to patients with PM-SAH. Patients with Fi3 had a high risk for early hydrocephalus, CVS, DCI, and an unfavorable outcome, similar to patients with aneurysmal SAH. After multivariate analysis, early hydrocephalus, elderly patients, and Fi3 were identified as negative prognostic factors. Therefore, patients with Fi3 are at risk and need careful clinical observation. PMID- 26847334 TI - Skyrmion motion driven by oscillating magnetic field. AB - The one-dimensional magnetic skyrmion motion induced by an electric current has attracted much interest because of its application potential in next-generation magnetic memory devices. Recently, the unidirectional motion of large (20 MUm in diameter) magnetic bubbles with two-dimensional skyrmion topology, driven by an oscillating magnetic field, has also been demonstrated. For application in high density memory devices, it is preferable to reduce the size of skyrmion. Here we show by numerical simulation that a skyrmion of a few tens of nanometres can also be driven by high-frequency field oscillations, but with a different direction of motion from the in-plane component of the tilted oscillating field. We found that a high-frequency field for small skyrmions can excite skyrmion resonant modes and that a combination of different modes results in a final skyrmion motion with a helical trajectory. Because this helical motion depends on the frequency of the field, we can control both the speed and the direction of the skyrmion motion, which is a distinguishable characteristic compared with other methods. PMID- 26847335 TI - Influence of verbal instructions on effect-based action control. AB - According to ideomotor theory, people use bidirectional associations between movements and their effects for action selection and initiation. Our experiments examined how verbal instructions of action effects influence response selection without prior experience of action effects in a separate acquisition phase. Instructions for different groups of participants specified whether they should ignore, attend, learn, or intentionally produce acoustic effects produced by button presses. Results showed that explicit instructions of action-effect relations trigger effect-congruent action tendencies in the first trials following the instruction; in contrast, no evidence for effect-based action control was observed in these trials when instructions were to ignore or to attend to the action effects. These findings show that action-effect knowledge acquired through verbal instruction and direct experience is similarly effective for effect-based action control as long as the relation between the movement and the effect is clearly spelled out in the instruction. PMID- 26847337 TI - Renal cell carcinoma recurrences and metastases in primary non-metastatic patients: a population-based study. AB - PURPOSE: To present the occurrence of metastases and local recurrences in primary non-metastatic patients with renal cell carcinoma (RCC) in a contemporary Swedish population-based cohort. METHODS: Between 2005 and 2009, a total of 4527 patients were included in the prospective National Swedish Kidney Cancer Register accounting for nearly all RCC patients in Sweden. Among M0 patients, 472 (13 %) had no follow-up data registered within 5-year follow-up time and were excluded from the analysis. RESULTS: In total, 939 (21 %) had distant metastases at presentation with a decrease from 23 to 18 % during the inclusion period. Of 3107 patients with follow-up data and with M0 disease, 623 (20 %) were diagnosed with a tumor recurrence during 5-year follow-up. Mean time to recurrence was 24 months (SD +/- 20 months). Among these, 570 patients (92 %) were at primary diagnosis treated with radical nephrectomy, 23 patients (3.7 %) with partial nephrectomy and 12 patients (1.9 %) with minimally invasive treatments. The most frequent sites of metastases were lung (54 %), lymph nodes (22 %) and bone (20 %). The treatment of recurrence was in 50 % systemic treatments, while metastasectomy was performed in 17 % of the patients, out of which 68 % were with a curative intention. CONCLUSIONS: In this population-based study, 21 % of the patients had metastatic disease at presentation, with a decreasing trend over the study period. During 5-year follow-up, 20 % of the primary non-metastatic patients had recurrent disease. Of the patients with recurrence, half were given systemic oncological treatment and 17 % underwent metastasectomy. PMID- 26847336 TI - Insights into numerical cognition: considering eye-fixations in number processing and arithmetic. AB - Considering eye-fixation behavior is standard in reading research to investigate underlying cognitive processes. However, in numerical cognition research eye tracking is used less often and less systematically. Nevertheless, we identified over 40 studies on this topic from the last 40 years with an increase of eye tracking studies on numerical cognition during the last decade. Here, we review and discuss these empirical studies to evaluate the added value of eye-tracking for the investigation of number processing. Our literature review revealed that the way eye-fixation behavior is considered in numerical cognition research ranges from investigating basic perceptual aspects of processing non-symbolic and symbolic numbers, over assessing the common representational space of numbers and space, to evaluating the influence of characteristics of the base-10 place-value structure of Arabic numbers and executive control on number processing. Apart from basic results such as reading times of numbers increasing with their magnitude, studies revealed that number processing can influence domain-general processes such as attention shifting-but also the other way round. Domain-general processes such as cognitive control were found to affect number processing. In summary, eye-fixation behavior allows for new insights into both domain-specific and domain-general processes involved in number processing. Based thereon, a processing model of the temporal dynamics of numerical cognition is postulated, which distinguishes an early stage of stimulus-driven bottom-up processing from later more top-down controlled stages. Furthermore, perspectives for eye-tracking research in numerical cognition are discussed to emphasize the potential of this methodology for advancing our understanding of numerical cognition. PMID- 26847338 TI - A comparison between an in vitro ureteroscopic stone size estimation and the stone size measurement with the help of a scale on stone baskets. AB - INTRODUCTION: Endoscopic treatment of ureter stones and renal calculi relies on the surgeon's estimation of the stone size for both lithotripsy and removal of stones or stone fragments. We therefore compared precision and reliability of the endoscopic estimation of stone size by the surgeon with measurements on a scale on a stone basket. MATERIALS AND METHODS: Two surgeons (one high experienced and one low experienced) first estimated, then measured the size of 12 stones differing in size and color using different stone baskets (2.5, 3.0, 4.0 Ch) each via a semirigid renoscope in an artificial ureter under water repeatedly on two different days. All together, we had 288 measurements and 288 estimations. RESULTS: On the whole, the accuracy of the estimation diminished with bigger stones. There is an increasing underestimation with increasing stone size. Factors, which significantly influence the estimation, are the operating surgeon, the color of the stone, the time sequence, and the size of the closed basket, which was held beside the stone. The accuracy of the measurement of the stone baskets is not as good as the estimation. The small 2.5-Ch basket is the most accurate in measuring big stones (>6 mm), the 3.5 Ch in intermediate stones (3-6 mm), the big basket (4.0 Ch) in small stones (<3 mm). CONCLUSION: This first attempt at validation of a scale on stone baskets shows different results for each basket which could be systematically improved. Until now, the estimation of the surgeons is better than the measurement, but it is also influenced by factors like the surgeon or the color of the stone. PMID- 26847340 TI - Combining glucose and sodium acetate improves the growth of Neochloris oleoabundans under mixotrophic conditions. AB - Mixotrophic cultivation is a potential approach to produce microalgal biomass that can be used as raw materials for renewable biofuels and animal feed, although using a suitable, cost-effective organic carbon source is crucial. Here, we used a Box-Behnken design with three factors, the glucose and sodium acetate concentrations, and the percentage of Bold's basal medium (BBM), to evaluate the effects of different carbon sources on biomass productivity and the protein and lipid contents of Neochloris oleoabundans (UTEX#1185). When grow at optimal levels of these factors, 100 % BBM plus 7.5 g L(-1) each of glucose and sodium acetate, N. oleoabundans yielded 1.75 g L(-1) of dry biomass, with 4.88 +/- 0.09 % N, 24.01 +/- 0.29-30.5 +/- 0.38 % protein, and 34.4 % +/- 0.81 lipids. A nuclear magnetic resonance spectrum ((1)H-NMR) of a lipid extract showed that the free fatty acid content was 11.25 %. Thus, combining glucose and sodium acetate during the mixotrophic cultivation of N. oleoabundans can yield greater amounts of biomass, proteins, and lipids for biofuel production. PMID- 26847339 TI - Is health-related quality of life between 90 and 180 days following stroke associated with long-term unmet needs? AB - PURPOSE: Understanding the relationship between health-related quality of life (HRQoL) and long-term unmet needs is important for guiding services to optimise life following stroke. We investigated whether HRQoL between 90 and 180 days following stroke was associated with long-term unmet needs. METHODS: Data from Australian Stroke Clinical Registry (AuSCR) registrants who participated in the Australian Stroke Survivor Needs Survey were used. Outcome data, including the EQ 5D, are routinely collected in AuSCR between 90 and 180 days post-stroke. Unmet needs were assessed at a median of 2 years and categorised into: health; everyday living; work/leisure; and support domains. Multivariable regression was used to determine associations between the EQ-5D dimensions and the likelihood of experiencing unmet needs and the visual analogue scale (VAS) (rating 0-100) and number of reported unmet needs. RESULTS: In total, 173 AuSCR registrants completed the Needs Survey (median age 69 years, 67 % male; 77 % ischaemic stroke). VAS scores were negatively associated with the number of reported long term unmet needs [irr 0.98, (95 % CI 0.97, 0 99) p < 0.001]. Having EQ-5D activity limitations was associated with unmet living needs (aOR 4.5, 95 % CI 1.1, 18.8). Requiring living supports at 90-180 days was associated with unmet health needs (aOR 4.9, 95 % CI 1.5, 16.1). Those with pain at 90-180 days were less likely to report unmet health (aOR 0.09, 95 % CI 0.02, 0.4) and support needs (aOR 0.2, 95 % CI 0.06, 0.6). CONCLUSION: Routinely collected HRQoL data can identify survivors at risk of experiencing long-term unmet needs. This information is important for targeting service delivery to optimise outcomes following stroke. PMID- 26847343 TI - Prepubertal exposure to T-2 toxin advances pubertal onset and development in female rats via promoting the onset of hypothalamic-pituitary-gonadal axis function. AB - T-2 toxin, a naturally produced Type A trichothecene mycotoxin, has been shown to damage the reproductive and developmental functions in livestocks. However, whether T-2 toxin can disturb the pubertal onset and development following prepubertal exposure remains unclear. To clarify this point, infantile female Sprague-Dawley rats were given a daily intragastric administration of vehicle or T-2 toxin at a dose of 375 MUg/kg body weight for 5 consecutive days from postnatal day (PND) 15-19 (PND15-PND19). The days of vaginal opening, first diestrus, and first estrus in regular estrous cycle were advanced following T-2 toxin treatment, indicating prepubertal exposure to T-2 toxin induced the advancement of puberty onset. The relative weights of uterus and ovaries and the incidence of corpora lutea were all increased in T-2 toxin-treated rats; serum hormone levels of luteinizing hormone and estradiol and the messenger RNA expressions of gonadotropin-releasing hormone (GnRH) and GnRH receptor also displayed marked increases following exposure to T-2 toxin, all of which were well consistent with the manifestations of the advanced puberty onset. In conclusion, the present study reveals that prepubertal exposure to a high level of T-2 toxin promotes puberty onset in infantile female rats by advancing the initiation of hypothalamic-pituitary-gonadal axis function in female rats. PMID- 26847341 TI - Chronological, geographical, and seasonal trends of human cases of avian influenza A (H5N1) in Vietnam, 2003-2014: a spatial analysis. AB - BACKGROUND: Human cases of highly pathogenic avian influenza A (H5N1) virus infection continue to occur in Southeast Asia. The objective of this study was to identify when and where human H5N1 cases have occurred in Vietnam and how the situation has changed from the beginning of the H5N1 outbreaks in 2003 through 2014, to assist with implementing methods of targeted disease management. METHODS: We assessed the disease clustering and seasonal variation of human H5N1 cases in Vietnam to evaluate the geographical and monthly timing trends. The clustering of H5N1 cases and associated mortality were examined over three time periods: the outbreak period (2003-2005), the post-outbreak (2006-2009), and the recent period (2010-2014) using the flexibly shaped space-time scan statistic. The most likely cases to co-cluster and the elevated risks for incidence and mortality were assessed via calculation of the relative risk (RR). The H5N1 case seasonal variation was analysed as the cyclic trend in incidence data using Roger's statistical test. RESULTS: Between 2003 and 2005, H5N1 cases (RR: 2.15, p = 0.001) and mortality (RR: 2.49, p = 0.021) were significantly clustered in northern Vietnam. After 2010, H5N1 cases tended to occur on the border with Cambodia in the south, while H5N1 mortality clustered significantly in the Mekong delta area (RR: 6.62, p = 0.002). A significant seasonal variation was observed (p < 0.001), with a higher incidence of morbidity in December through April. CONCLUSIONS: These findings indicate that clinical preparedness for H5N1 in Vietnam needs to be strengthened in southern Vietnam in December-April. PMID- 26847342 TI - Serotonin promotes exploitation in complex environments by accelerating decision making. AB - BACKGROUND: Fast responses can provide a competitive advantage when resources are inhomogeneously distributed. The nematode Caenorhabditis elegans was shown to modulate locomotion on a lawn of bacterial food in serotonin (5-HT)-dependent manners. However, potential roles for serotonergic signaling in responding to food discovery are poorly understood. RESULTS: We found that 5-HT signaling in C. elegans facilitates efficient exploitation in complex environments by mediating a rapid response upon encountering food. Genetic or cellular manipulations leading to deficient serotonergic signaling resulted in gradual responses and defective exploitation of a patchy foraging landscape. Physiological imaging revealed that the NSM serotonergic neurons responded acutely upon encounter with newly discovered food and were key to rapid responses. In contrast, the onset of responses of ADF serotonergic neurons preceded the physical encounter with the food. The serotonin-gated chloride channel MOD-1 and the ortholog of mammalian 5 HT1 metabotropic serotonin receptors SER-4 acted in synergy to accelerate decision-making. The relevance of responding rapidly was demonstrated in patchy environments, where the absence of 5-HT signaling was detrimental to exploitation. CONCLUSIONS: Our results implicate 5-HT in a novel form of decision making, demonstrate its fitness consequences, suggest that NSM and ADF act in concert to modulate locomotion in complex environments, and identify the synergistic action of a channel and a metabotropic receptor in accelerating C. elegans decision-making. PMID- 26847345 TI - Transgelin increases metastatic potential of colorectal cancer cells in vivo and alters expression of genes involved in cell motility. AB - BACKGROUND: Transgelin is an actin-binding protein that promotes motility in normal cells. Although the role of transgelin in cancer is controversial, a number of studies have shown that elevated levels correlate with aggressive tumor behavior, advanced stage, and poor prognosis. Here we sought to determine the role of transgelin more directly by determining whether experimental manipulation of transgelin levels in colorectal cancer (CRC) cells led to changes in metastatic potential in vivo. METHODS: Isogenic CRC cell lines that differ in transgelin expression were characterized using in vitro assays of growth and invasiveness and a mouse tail vein assay of experimental metastasis. Downstream effects of transgelin overexpression were investigated by gene expression profiling and quantitative PCR. RESULTS: Stable overexpression of transgelin in RKO cells, which have low endogenous levels, led to increased invasiveness, growth at low density, and growth in soft agar. Overexpression also led to an increase in the number and size of lung metastases in the mouse tail vein injection model. Similarly, attenuation of transgelin expression in HCT116 cells, which have high endogenous levels, decreased metastases in the same model. Investigation of mRNA expression patterns showed that transgelin overexpression altered the levels of approximately 250 other transcripts, with over representation of genes that affect function of actin or other cytoskeletal proteins. Changes included increases in HOOK1, SDCCAG8, ENAH/Mena, and TNS1 and decreases in EMB, BCL11B, and PTPRD. CONCLUSIONS: Increases or decreases in transgelin levels have reciprocal effects on tumor cell behavior, with higher expression promoting metastasis. Chronic overexpression influences steady-state levels of mRNAs for metastasis-related genes. PMID- 26847347 TI - 'The bills that were coming in...': out of pocket costs during relocation for specialist treatment for haematological malignancies. AB - PURPOSE: This paper responds to the call for more research to fully understand out of pocket (OOP) costs for cancer patients by providing a detailed discussion of such costs for adult haematology patients from Queensland, Australia. METHODS: The descriptive qualitative research was based on in-depth interviews with 45 (n = 45) haematology patients from regional, rural and remote areas. RESULTS: The discussion itemises the OOP costs under four categories including the costs associated with travel and accommodation, the costs associated with family and friends during relocation, the costs associated with diagnosis and treatment, and the costs of parking. CONCLUSIONS: The paper provides evidence of the categories of financial burden experienced by haematology patients who have to relocate for specialist treatment by detailing the extensive range of OOP costs. The expectation is that the itemisation of OOP cost variables will contribute to future efforts of quantification. PMID- 26847346 TI - Genetic diversity and natural selection in the rhoptry-associated protein 1 (RAP 1) of recent Plasmodium knowlesi clinical isolates from Malaysia. AB - BACKGROUND: The Plasmodium rhoptry-associated protein 1 (RAP-1) plays a role in the formation of the parasitophorous vacuole following the parasite's invasion of red blood cells. Although there is some evidence that the protein is recognized by the host's immune system, study of Plasmodium falciparum RAP-1 (PfRAP-1) suggests that it is not under immune pressure. A previous study on five old (1953 1962) P. knowlesi strains suggested that RAP-1 has limited genetic polymorphism and might be under negative selection. In the present study, 30 recent P. knowlesi isolates were studied to obtain a better insight into the polymorphism and natural selection of PkRAP-1. METHODS: Blood samples from 30 knowlesi malaria patients were used. These samples were collected between 2010 and 2014. The PkRAP 1 gene, which contains two exons, was amplified by PCR, cloned into Escherichia coli and sequenced. Genetic diversity and phylogenetic analyses were performed using MEGA6 and DnaSP ver. 5.10.00 programs. RESULTS: Thirty PkRAP-1 sequences were obtained. The nucleotide diversity (pi) of exons 1, 2 and the total coding region (0.00915, 0.01353 and 0.01298, respectively) were higher than those of the old strains. Further analysis revealed a lower rate of non-synonymous (dN) than synonymous (dS) mutations, suggesting negative (purifying) selection of PkRAP-1. Tajima's D test and Fu and Li's D test values were not significant. At the amino acid level, 22 haplotypes were established with haplotype H7 having the highest frequency (7/34, 20.5 %). In the phylogenetic analysis, two distinct haplotype groups were observed. The first group contained the majority of the haplotypes, whereas the second had fewer haplotypes. CONCLUSIONS: The present study found higher genetic polymorphism in the PkRAP-1 gene than the polymorphism level reported in a previous study. This observation may stem from the difference in sample size between the present (n = 30) and the previous (n = 5) study. Synonymous and non-synonymous mutation analysis indicated purifying (negative) selection of the gene. The separation of PkRAP-1haplotypes into two groups provides further evidence to the postulation of two distinct P. knowlesi types or lineages. PMID- 26847348 TI - Assessing anxiety in Black men with prostate cancer: further data on the reliability and validity of the Memorial Anxiety Scale for Prostate Cancer (MAX PC). AB - PURPOSE: The National Cancer Institute has highlighted the need for psychosocial research to focus on Black cancer patients. This applies to Black men with prostate cancer, as there is little systematic research concerning psychological distress in these men. This study was designed to validate the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) in Black men with prostate cancer to help facilitate research within this group. METHODS: At three institutions, Black men with prostate cancer (n = 101) completed the MAX-PC, the Hospital Anxiety and Depression Scale (HADS), the Functional Assessment of Cancer Therapy (FACT) Quality of Life Questionnaire, and the Distress Thermometer. RESULTS: The average age of the 101 men was 66 (SD = 10) and 58 % had early-stage disease. The MAX-PC and its subscales (Prostate Cancer Anxiety, PSA Anxiety, and Fear of Recurrence) produced strong coefficient alphas (0.89, 0.88, 0.71, and 0.77, respectively). Factor analysis supported the three-factor structure of the scale established in earlier findings. The MAX-PC also demonstrated strong validity. MAX-PC total scores correlated highly with the Anxiety subscale of the HADS (r = 0.59, p < 0.01) and the FACT Emotional Well-Being subscale (r = -0.55, p < 0.01). Demonstrating discriminant validity, the correlation with the HADS Depression subscale (r = 0.40, p < 0.01) and the CES-D (r = 0.42, p < 0.01) was lower compared to that with the HADS Anxiety subscale. CONCLUSIONS: The MAX-PC is valid and reliable in Black men with prostate cancer. We hope the validation of this scale in Black men will help facilitate psychosocial research in this group that is disproportionately adversely affected by this cancer. PMID- 26847349 TI - Occurrence and characterization of everolimus adverse events during first and subsequent cycles in the treatment of metastatic breast cancer. AB - PURPOSE: Endocrine therapy remains the standard therapy for patients with metastatic hormone receptor (HR)-positive breast cancer. The novel combination of everolimus and exemestane has been shown to prolong progression-free survival but with increased adverse events compared to exemestane alone. In this study, we aimed to describe the frequency and timing of everolimus dose reductions and/or interruptions due to adverse events. METHODS: This is a single-center retrospective case series including all patients who received everolimus in combination with exemestane from May 1, 2012, through July 31, 2013. The primary objective was to determine the incidence of first-cycle interruptions or dose reductions with everolimus. RESULTS: Forty-six patients were included in the analysis. First-cycle dose reductions or interruptions were observed in 21 (45.6 %) patients. The most common adverse events leading to dose reduction or interruption was stomatitis (57.1 %), fatigue (14.3 %), and diarrhea (14.3 %). The median time to dose reduction was 14 days, and the median duration of the interruption was 14 days. The median progression-free survival was 6.2 months, and the median time to treatment failure was 4.4 months. CONCLUSIONS: In this case series, almost half of the patients treated with everolimus and exemestane required a dose reduction or interruption of everolimus during the first cycle of treatment. This early onset of adverse events requires thorough patient education and close clinical monitoring during the first 28 days of therapy. PMID- 26847350 TI - Exercise motivation in rectal cancer patients during and after neoadjuvant chemoradiotherapy. AB - PURPOSE: Aerobic exercise is safe and feasible for rectal cancer patients during and after neoadjuvant chemoradiotherapy (NACRT), but their motivation to perform such exercise is unknown. Here, we explore the motivational outcomes, perceived benefits and harms, and perceived barriers to exercise during and after NACRT. METHODS: Rectal cancer patients (n = 18) participated in supervised aerobic exercise during NACRT followed by unsupervised exercise after NACRT. Using the theory of planned behavior, we assessed perceived benefits, harms, enjoyment, support, difficulty, and barriers for exercise both during and after NACRT. RESULTS: Patients reported that exercise during NACRT was more enjoyable (p = 0.003) and less difficult (p = 0.037) than initially anticipated. The most common perceived benefits of exercise during NACRT were cardiovascular endurance (75 %), quality of life (75 %), and self-esteem (65 %). After NACRT, the most common perceived benefits were physical functioning (93 %), cardiovascular endurance (86 %), and quality of life (79 %). The most common perceived harms of exercise during NACRT were fatigue (31 %), diarrhea (31 %), and skin irritation (24 %). After NACRT, the most common perceived harms were fatigue (21 %) and hand-foot syndrome (15 %). Side effects from NACRT were the most common exercise barrier during NACRT (88 %) whereas lack of motivation was the most common barrier after NACRT (79 %). CONCLUSIONS: Rectal cancer patients reported aerobic exercise during NACRT to be more enjoyable and less difficult than anticipated despite significant barriers. This positive motivational response may facilitate recruitment and adherence in future interventions. Moreover, rectal cancer patients identified potential benefits and harms that should be closely monitored in future interventions. PMID- 26847352 TI - Comparison of Risk Factors for Unplanned Conversion from Laparoscopic and Robotic to Open Colorectal Surgery Using the Michigan Surgical Quality Collaborative (MSQC) Database. AB - Robotic colorectal surgery has been shown to have lower rates of unplanned conversion to open surgery when compared to laparoscopic surgery. Risk factors associated with conversion from robotic to open colectomy and comparisons of the risk factors between robotic and laparoscopic approaches have not been previously reported. Patients who underwent elective laparoscopic and robotic colorectal surgeries between July 1, 2012 and April 28, 2015, were identified in the Michigan Surgical Quality Collaborative registry. Candidate covariates were identified, and hierarchical logistic regression models were used to identify risk factors for conversion. There were 4796 cases that met study inclusion criteria. Conversion was required in 18.2 % of laparoscopic and 7.7 % of robotic cases (p < 0.0001). Risk factors for conversion in the laparoscopic group included the following: moderate/severe adhesions, obesity, colorectal cancer, hypertension, rectal operations, urgent priority, and tobacco use. Risk factors for conversion in the robotic group included the following: severe adhesions, bleeding disorder, presence of cancer, cirrhosis, and use of statins. Higher surgeon volume was protective in both groups. Conversion rates are lower for robotic than for laparoscopic colorectal surgery with fewer predictors of conversion. Recognition of factors predicting conversion may allow surgeons to choose an operative approach that optimizes the benefits of the available technologies. PMID- 26847351 TI - Transcriptional repression of SOCS3 mediated by IL-6/STAT3 signaling via DNMT1 promotes pancreatic cancer growth and metastasis. AB - BACKGROUND: Previous studies have investigated the sustained aberrantly activated Interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) signaling pathway is crucial for pancreatic cancer growth and metastasis. Suppressor of cytokine signaling 3 (SOCS3), as a key negative feedback regulator of this signaling pathway, is usually down-regulated in various cancers. In the present study, we aim at exploring the biological function and the underlying molecular regulation mechanisms of SOCS3 in pancreatic cancer. METHODS: The expression of SOCS3 and other genes in pancreatic cancer was examined by Quantitative real-time PCR, western blotting and immunohistochemical staining. The interaction between pSTAT3 and DNA Methyltransferase 1 (DNMT1) was investigated by co-immunoprecipitation assay. Luciferase reporter assay was used to investigate the transcriptional regulation of pSTAT3 and DNMT1 on the SOCS3 gene. The effects of SOCS3 on the biological behavior of pancreatic cancer cells were assessed both in vitro and vivo. Furthermore, we performed a comprehensive analysis of the expression of SOCS3 in a pancreatic cancer tissue microarray (TMA) and correlated our findings with pathological parameters and outcomes of the patients. RESULTS: We showed that SOCS3 expression was decreased in phosphorylated STAT3 (pSTAT3)-positive tumors and was negatively correlated with pSTAT3 in pancreatic cancer cells. We also found that IL-6/STAT3 promoted SOCS3 promoter hypermethylation by increasing DNMT1 activity; silencing DNMT1 or 5-aza 2-deoxycytidine (5-AZA) treatment could reverse the down-regulation of SOCS3 mediated by IL-6. Using co-immunoprecipitation and luciferase reporter assays, we found that STAT3 recruited DNMT1 to the promoter region of SOCS3 and inhibited its transcriptional activity. Overexpression of SOCS3 significantly inhibited cell proliferation, which may be due to the increase in G1-S phase arrest; overexpression of SOCS3 also inhibited cell migration and invasion as well as tumorigenicity in nude mice. Pancreatic cancer tissue microarray analysis showed that high SOCS3 expression was a good prognostic factor and negatively correlated with tumor volume and metastasis. CONCLUSION: We demonstrated that activated IL 6/STAT3 signaling could induce SOCS3 methylation via DNMT1, which led to pancreatic cancer growth and metastasis. These data also provided a mechanistic link between sustained aberrantly activated IL-6/STAT3 signaling and SOCS3 down regulation in pancreatic cancer. Thus, inhibitors of STAT3 or DNMT1 may become novel strategies for treating pancreatic cancer. PMID- 26847353 TI - Hepatectomy After Yttrium-90 (Y90) Radioembolization-Induced Liver Fibrosis. AB - An obese 55-year-old woman with nonalcoholic fatty liver disease presented 7 years after resection of a T3N1 ileal carcinoid tumor with an elevated chromogranin A, multifocal metastatic disease to the liver, and carcinoid syndrome. She underwent right hepatic artery yttrium-90 (Y90) radioembolization, followed a month later by selective Y90 treatment to segment IV. She then presented to our clinic 10 months later, remaining symptomatic with flushing, diarrhea, anxiety, myalgia, pain, and persistent night sweats despite Sandostatin administration. At least 11 tumors were identified in the right lobe of the liver and three in segment IV on liver-specific imaging. These lesions were stable over a year with no new lesions. At exploration, there was marked hypertrophy of the left lateral segment due to the yttrium-90 treatment of segments IV-VIII, corresponding with preoperative volumetrics predicting a functional liver remnant (FLR) of 40% after extended right hepatectomy. The right lobe and segment IV were fibrotic, hard, and visibly damaged. The gland had a thick, fibrotic capsule, and the parenchyma was dense, inflexible, and difficult to dissect, consistent with the previously reported morbidity of these operations. Extended right hepatectomy was performed. Final pathology demonstrated 15 foci of metastatic well differentiated neuroendocrine carcinoma that were negative for necrosis, as was expected given her continued symptoms despite radioembolization. Numerous amorphous spheres, frequently in clusters, were present in segments IV-VIII in vessels and approximating tumors consistent with prior Y90 radioembolization. The patient had an uneventful post-operative recovery and remains symptom free on follow-up. Treatment options for metastatic tumors to the liver have increased in recent years and currently include radioembolization in selected patients. Surgical cytoreduction and complete metastasectomy continue to offer improvement in symptoms, quality of life, and survival in patients with neuroendocrine liver metastases; however, hepatectomy after radioembolization is unique and carries increased morbidity/mortality, likely due to Y90-induced liver fibrosis. We demonstrate images of fibrotic yttrium-90 radiation-affected liver and histological sections of radioembolic microbeads in blood vessels and distributed around resected tumors. PMID- 26847354 TI - Type VII Secretion Systems in Gram-Positive Bacteria. AB - Bacterial secretion systems are sophisticated molecular machines that fulfil a wide range of important functions, which reach from export/secretion of essential proteins or virulence factors to the implication in conjugation processes. In contrast to the widely distributed Sec and Twin Arginine Translocation (TAT) systems, the recently identified ESX/type VII systems show a more restricted distribution and are typical for mycobacteria and other high-GC Actinobacteria. Similarly, type VII-like secretion systems have been described in low-GC Gram positive bacteria belonging to the phylum Firmicutes. While the most complex organization of type VII secretion systems currently known is found in slow growing mycobacteria, which harbour up to 5 chromosomal-encoded systems (ESX-1 to ESX-5), much simpler organization is reported for type VII-like systems in Firmicutes. In this chapter, we describe common and divergent features of type VII- and type VII-like secretion pathways and also comment on their biological key roles, many of which are related to species-/genus-specific host-pathogen interactions and/or virulence mechanisms. PMID- 26847355 TI - Pilus Assembly in Gram-Positive Bacteria. AB - Pili of Gram-positive bacteria are unique structures on the bacterial surface, assembled from covalently linked polypeptide subunits. Pilus assembly proceeds by transpeptidation reactions catalyzed by sortases, followed by covalent anchoring of the filament in the peptidoglycan layer. Another distinctive property is the presence of intramolecular isopeptide bonds, conferring extraordinary chemical and mechanical stability to these elongated structures. Besides their function in cell adhesion and biofilm formation, this section discusses possible application of pilus constituents as vaccine components against Gram-positive pathogens. PMID- 26847356 TI - Taxonomy of Histophilus somni. AB - Histophilus somni was proposed in 2003 as a common name for bacteria that earlier had been called "Haemophilus somni", "Haemophilus agni", "Haemophilus somnifer", and "Histophilus ovis". The species is clearly separated from other species and genera within the family Pasteurellaceae. The species is phenotypically variable, but highly uniform regarding the 16S rDNA sequence. Whole-genome sequencing has revealed distinct genetic differences between a commensal and a pathogenic strain, particularly in regard to putative virulence factors. However, broad generalizations regarding the genetics of H. somni cannot be applied to the entire species until the genomes of additional strains are sequenced. PMID- 26847357 TI - Histophilosis as a Natural Disease. AB - Histophilus somni is responsible for sporadic disease worldwide in cattle and, to a lesser extent, in small ruminants, bighorn sheep (Ovis canadensis), and North American bison (Bison bison). The importance of H. somni diseases can be attributed to improved clinical and laboratory recognition, combined with the growth in intensive management practices for cattle. Although outbreaks of bovine histophilosis can occur year-round, in northern and southern hemispheres, it is most frequent in late fall and early winter. Weather, stress, dietary changes, and comingling of cattle are likely to be major triggers for outbreaks. The most frequent clinical expressions of histophilosis include undifferentiated fever, fibrinosuppurative pneumonia, encephalitis-leptomeningitis, necrotizing myocarditis, and diffuse pleuritis. Neurological disease occurs either as thrombotic meningoencephalitis (TME) or as suppurative meningitis with ventriculitis. Acute myocarditis is characteristically necrotizing and generally involves one or both papillary muscles in the left ventricular myocardium. Biofilm-like aggregates of bacteria occur in capillaries and veins in myocardium, in the central nervous system, and on endocardial surfaces. H. somni is a component of bovine respiratory disease (BRD) complex. In our experience, it is most commonly diagnosed in subacute-to-chronic polymicrobial pulmonary infections in combination with Mannheimia haemolytica, Trueperella pyogenes, Pasteurella multocida, or Mycoplasma bovis. Other, less common forms of H. somni disease present as polyarthritis/tenosynovitis, abortion with placentitis and fetal septicemia, epididymitis-orchitis, and ocular infections. It is likely that H. somni is under-recognized clinically and diagnostically. Most state and provincial laboratories in North America rely on bacterial isolation to confirm infection. The use of more sensitive detection methods on field cases of histophilosis will help resolve the pathogenesis of H. somni in natural outbreaks, and whether the disease is as common elsewhere as it is in Canada. PMID- 26847358 TI - Advances in Therapeutic Drug Monitoring of Biologic Therapies in Inflammatory Bowel Disease: 2015 in Review. AB - OPINION STATEMENT: Monoclonal antibody therapy directed against tumor necrosis factor-alpha (anti-TNFs) has revolutionized the care of patients with Crohn's disease and ulcerative colitis. These large proteins are potentially immunogenic. Early clinical trials demonstrated an association with both serum concentrations of these agents as well as the presence of antidrug antibodies generated by the host with loss of response. More recent research has provided further evidence to confirm the impact of low drug trough concentrations and antidrug antibodies on subsequent clinical course in CD and UC. Given these clinical implications, treatment algorithms have been developed to aid clinicians in interpreting trough drug levels and antibody concentrations in those with confirmed active disease. Several studies have demonstrated the utility of these approaches. Furthermore, there are growing data supporting the use of therapeutic drug monitoring in a prospective fashion in those patients who are clinically stable on anti-TNF therapies to ensure they are receiving appropriate dosing and have not yet developed antibodies. In addition, for those who have developed low-level antibodies, increasing the dose of an anti-TNF or adding an immunomodulator may help to overcome this immunologic response. Further research is required to assess these proposed strategies, as well as to determine the role of trough drug level assessment and antibody testing for new anti-TNFs and biologic medication with alternative mechanisms of action. PMID- 26847359 TI - Evaluation and Management of Infectious Esophagitis in Immunocompromised and Immunocompetent Individuals. AB - OPINION STATEMENT: Among the many inflammatory processes that may account for esophageal symptoms, infection represents an important etiologic category with numerous clinically relevant subdivisions. While features of the history and physical exam are informative, diagnosis often hinges on endoscopic visualization and histopathologic analysis. This chapter will review in series the most clinically relevant causative agents for infectious esophagitis, with specific diagnostic and therapeutic features of note divided into one of two immune milieus. Our discussion focuses primarily on Candida species, herpes simplex virus, and cytomegalovirus as the most common causes of infectious esophagitis while also addressing a number of less common pathogens worth keeping in mind. PMID- 26847360 TI - Trying to see, failing to focus: near visual impairment in Down syndrome. AB - The majority of individuals with Down syndrome (DS) do not exhibit accurate accommodation, with the aetiology of this deficit unknown. This study examines the mechanism underlying hypoaccommodation in DS by simultaneously investigating the 'near triad' - accommodation, vergence and pupillary response. An objective photorefraction system measured accommodation, pupil size and gaze position (vergence) under binocular conditions while participants viewed an animated movie at 50, 33, 25 and 20 cm. Participants were aged 6-16 years (DS = 41, controls = 76). Measures were obtained from 59% of participants with DS and 99% of controls. Accommodative response was significantly less in DS (p < 0.001) and greater accommodative deficits were associated with worsening visual acuity (p = 0.02). Vergence responses were as accurate in DS as in controls (p = 0.90). Habitual pupil diameter did not differ between groups (p = 0.24) but reduced significantly with increasing accommodative demand in both participants with and without DS (p < 0.0001). This study is the first to report simultaneous binocular measurement of the near triad in DS demonstrating that hypoaccommodation is linked to poor visual acuity. Vergence responses were accurate indicating that hypoaccommodation cannot be dismissed as a failure to visually engage with near targets, but rather is a consequence of underlying neurological or physiological deficits. PMID- 26847361 TI - Casamino acids facilitate the secretion of recombinant dengue virus serotype-3 envelope domain III in Pichia pastoris. AB - BACKGROUND: Dengue is a viral disease spread to humans by mosquitoes. Notably, there are four serotypes of dengue viruses (DENV) that places ~40 % of the global population at risk of infection. However, lack of a suitable drug or a preventive vaccine exacerbates the matter further. Envelope domain-III (EDIII) antigen of dengue virus (DENV) has garnered much attention as a promising vaccine candidate for dengue, in addition to its use as a diagnostic intermediate. Hence developing a method for efficient production of high quality recombinant EDIII is important for research and industrial purpose. RESULTS: In this work, a Pichia pastoris system was optimized for the secretory over-expression of DENV serotype-3 EDIII under the control of methanol inducible AOX1 promoter. Temperature alone had a significant impact upon the amount of secretory EDIII, with 2.5-fold increase upon reducing the induction temperature from 30 to 20 degrees C. However surprisingly, supplementation of culture media with Casamino acids (CA), further augmented secretory EDIII titer, with a concomitant drop of intracellular EDIII levels at both temperatures. Though, reduction in intracellular retention of EDIII was more prominent at 20 degrees C than 30 degrees C. This suggests that CA supplementation facilitates overexpressing P. pastoris cells to secrete more EDIII by reducing the proportion retained intracellularly. Moreover, a bell shaped correlation was observed between CA concentration and secretory EDIII titer. The maximum EDIII expression level of 187 mg/L was achieved under shake flask conditions with induction at 20 degrees C in the presence of 1 % CA. The overall increase in EDIII titer was ~9-fold compared to un-optimized conditions. Notably, mouse immune-sera, generated using this purified EDIII antigen, efficiently neutralized the DENV. CONCLUSIONS: The strategy described herein could enable fulfilling the mounting demand for recombinant EDIII as well as lay direction to future studies on secretory expression of recombinant proteins in P. pastoris with CA as a media supplement. PMID- 26847362 TI - American Society of Nephrology Quiz and Questionnaire 2015: Glomerular Diseases. AB - The Nephrology Quiz and Questionnaire remains an extremely popular session for attendees of the annual Kidney Week meeting of the American Society of Nephrology. Once again, the conference hall was overflowing with audience members and eager quiz participants. Topics covered by the expert discussants included electrolyte and acid-base disorders, glomerular disease, ESRD/dialysis, and kidney transplantation. Complex cases representing each of these categories, along with single-best-answer questions, were prepared and submitted by the panel of experts. Before the meeting, training program directors of United States nephrology fellowship programs and nephrology fellows answered the questions through an Internet-based questionnaire. During the live session, members of the audience tested their knowledge and judgment on a series of case-oriented questions prepared and discussed by the experts. They compared their answers in real time using their cell phones with a special app with the answers of the nephrology fellows and training program directors. The correct and incorrect answers were then discussed after the results of the questionnaire were displayed. As always, the audience, lecturers, and moderators enjoyed this educational session. This article recapitulates the session and reproduces its educational value for Clinical Journal of the American Society of Nephrology readers. Enjoy the clinical cases and expert discussions. PMID- 26847363 TI - [Cancer screening in venous thromboembolism of unknown origin]. PMID- 26847364 TI - [Current therapeutic strategies for diffuse large B-cell lymphoma]. AB - Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. The incorporation of the CD20 antibody rituximab into CHOP polychemotherapy at the beginning of this century has considerably improved the outcome of all patients with DLBCL. Nowadays, depending on the prognostic subgroup less than one half to one third of patients die from DLBCL compared to the pre-rituximab era. Treatment is usually tailored to the individual risk profile of DLBCL patients according to the international prognostic index (IPI). Assignment of a DLBCL according to the gene expression profile to a DLBLC originating from a germinal center B-cell (GC type) or from an activated B-cell (ABC type) has provided novel insights into the pathogenesis of the respective DLBCL and identified molecules which are indispensable for the formation and growth of a DLBCL, thus providing targets for novel targeted therapies. Incorporating these new drugs into the current internationally recognized combination immunochemotherapy R-CHOP or substituting single drugs in the R-CHOP combination will result in even higher survival rates and reduction of therapeutic side effects in patients with DLBCL in the coming years. PMID- 26847365 TI - The crowded crossroad to angiogenesis in systemic sclerosis: where is the key to the problem? AB - In systemic sclerosis (SSc), peripheral vasculopathy is characterized by a progressive and irreversible loss of capillaries following endothelial cell injury, due to defects in both vascular repair and expected increase in new vessel growth (angiogenesis). The discovery of key molecular targets may help to develop the most effective therapeutic strategy for the SSc-related vasculopathy. A pathway worth targeting in SSc may include vascular endothelial growth factor, 165b isoform, an endogenous angiogenesis inhibitor abnormally expressed and released by different cell types, including activated endothelial cells and platelets. PMID- 26847366 TI - Analytical performance evaluation of a high-volume hematology laboratory utilizing sigma metrics as standard of excellence. AB - INTRODUCTION: Around two-thirds of important clinical decisions about the management of patients are based on laboratory test results. Clinical laboratories are required to adopt quality control (QC) measures to ensure provision of accurate and precise results. Six sigma is a statistical tool, which provides opportunity to assess performance at the highest level of excellence. The purpose of this study was to assess performance of our hematological parameters on sigma scale in order to identify gaps and hence areas of improvement in patient care. METHODS: Twelve analytes included in the study were hemoglobin (Hb), hematocrit (Hct), red blood cell count (RBC), mean corpuscular volume (MCV), red cell distribution width (RDW), total leukocyte count (TLC) with percentages of neutrophils (Neutr%) and lymphocytes (Lymph %), platelet count (Plt), mean platelet volume (MPV), prothrombin time (PT), and fibrinogen (Fbg). Internal quality control data and external quality assurance survey results were utilized for the calculation of sigma metrics for each analyte. RESULTS: Acceptable sigma value of >=3 was obtained for the majority of the analytes included in the analysis. MCV, Plt, and Fbg achieved value of <3 for level 1 (low abnormal) control. PT performed poorly on both level 1 and 2 controls with sigma value of <3. CONCLUSIONS: Despite acceptable conventional QC tools, application of sigma metrics can identify analytical deficits and hence prospects for the improvement in clinical laboratories. PMID- 26847367 TI - Color-Transformable Silicone Elastomers Prepared by Thiol-Ene Reaction with Potential Application in UV-LEDs. AB - A series of high-efficiency, full-color fluorescent elastomers based on polysiloxane matrix prepared by an easy thiol-ene "click" reaction is reported here. It is found for the first time that the same elastomer can emit transformable colors by conveniently altering the excitation wavelength because of the effect of energy transfer and the "fluorescence switch" of lanthanide ions. A fluent change in emission colors can also be feasible and conveniently reproducible by varying the stoichiometric ratio of lanthanide ions and rhodamine B in solution and in polymer elastomers. The obtained elastomers are further coated onto commercially available UV-LED cells from the solution medium followed by an in situ cross-linking step. PMID- 26847368 TI - A randomised trial of placing preterm infants on their back or left side after birth. AB - BACKGROUND: Basic life support guidelines recommend placing spontaneously breathing children and adults on their side. Though the majority of preterm newborns breathe spontaneously, they are routinely placed on their back after birth. We hypothesised that they would breathe more effectively when placed on their side. OBJECTIVE: To determine whether preterm newborns placed on their left side at birth, compared with those placed on their back, have higher preductal oxygen saturation (SpO2) at 5 min of life. DESIGN/METHODS: We randomised infants <32 weeks to be placed on their back or on their left side immediately after birth. Respiratory support was given with a T-piece and face mask with initial fraction of inspired oxygen (FiO2) of 0.3. The FiO2 was increased if SpO2 was <70% at 5 min. RESULTS: We enrolled 87 infants, 41 randomised to back and 46 to left side. The groups were well matched for demographic variables. Fourteen (6 back and 8 left side) infants did not receive respiratory support in the first 5 min. The mean (SD) SpO2 was not different between the groups (back 72 (23) % versus left side 71 (24) %, p=0.956). We observed no adverse effects of placing infants on their side and found no differences in secondary outcomes between the groups. CONCLUSIONS: Preterm infants on their left side did not have higher SpO2 at 5 min of life. Placing preterm infants on their side at birth is feasible and appears to be a reasonable alternative to placing them on their back. TRIAL REGISTRATION NUMBER: ISRCTN74486341. PMID- 26847369 TI - A new suction mask to reduce leak during neonatal resuscitation: a manikin study. AB - OBJECTIVE: Leak around the face mask is a common problem during neonatal resuscitation. A newly designed face mask using a suction system to enhance contact between the mask and the infant's face might reduce leak and improve neonatal resuscitation. The aim of the study is to determine whether leak is reduced using the suction mask (Resusi-sure mask) compared with a conventional mask (Laerdal Silicone mask) in a manikin model. METHODS: Sixty participants from different professional categories (neonatal consultants, fellows, registrars, nurses, midwives and students) used each face mask in a random order to deliver 2 min of positive pressure ventilation to a manikin. Delivered airway pressures were measured using a pressure line. Inspiratory and expiratory flows were measured using a flow sensor, and expiratory tidal volumes and mask leaks were derived from these values. RESULTS: A median (IQR) leak of 12.1 (0.6-39.0)% was found with the conventional mask compared with 0.7 (0.2-4.6)% using the suction mask (p=0.002). 50% of the participants preferred to use the suction mask and 38% preferred to use the conventional mask. There was no correlation between leak and operator experience. CONCLUSIONS: A new neonatal face mask based on the suction system reduced leak in a manikin model. Clinical studies to test the safety and effectiveness of this mask are needed. PMID- 26847370 TI - "Atrio-atrial pacing" as a treatment for electrical dissociation after catheter ablation. PMID- 26847373 TI - Parents' depression is linked to worse school performance in children. PMID- 26847371 TI - Assessing parallel gene histories in viral genomes. AB - BACKGROUND: The increasing abundance of sequence data has exacerbated a long known problem: gene trees and species trees for the same terminal taxa are often incongruent. Indeed, genes within a genome have not all followed the same evolutionary path due to events such as incomplete lineage sorting, horizontal gene transfer, gene duplication and deletion, or recombination. Considering conflicts between gene trees as an obstacle, numerous methods have been developed to deal with these incongruences and to reconstruct consensus evolutionary histories of species despite the heterogeneity in the history of their genes. However, inconsistencies can also be seen as a source of information about the specific evolutionary processes that have shaped genomes. RESULTS: The goal of the approach here proposed is to exploit this conflicting information: we have compiled eleven variables describing phylogenetic relationships and evolutionary pressures and submitted them to dimensionality reduction techniques to identify genes with similar evolutionary histories. To illustrate the applicability of the method, we have chosen two viral datasets, namely papillomaviruses and Turnip mosaic virus (TuMV) isolates, largely dissimilar in genome, evolutionary distance and biology. Our method pinpoints viral genes with common evolutionary patterns. In the case of papillomaviruses, gene clusters match well our knowledge on viral biology and life cycle, illustrating the potential of our approach. For the less known TuMV, our results trigger new hypotheses about viral evolution and gene interaction. CONCLUSIONS: The approach here presented allows turning phylogenetic inconsistencies into evolutionary information, detecting gene assemblies with similar histories, and could be a powerful tool for comparative pathogenomics. PMID- 26847372 TI - The effect of heat stress on gene expression, synthesis of steroids, and apoptosis in bovine granulosa cells. AB - Summer heat stress (HS) is a major contributing factor in low fertility in lactating dairy cows in hot environments. Heat stress inhibits ovarian follicular development leading to diminished reproductive efficiency of dairy cows during summer. Ovarian follicle development is a complex process. During follicle development, granulosa cells (GCs) replicate, secrete hormones, and support the growth of the oocyte. To obtain an overview of the effects of heat stress on GCs, digital gene expression profiling was employed to screen and identify differentially expressed genes (DEGs; false discovery rate (FDR) <= 0.001, fold change >=2) of cultured GCs during heat stress. A total of 1211 DEGs including 175 upregulated and 1036 downregulated ones were identified, of which DEGs can be classified into Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results suggested that heat stress triggers a dramatic and complex program of altered gene expression in GCs. We hypothesized that heat stress could induce the apoptosis and dysfunction of GCs. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of steroidogenic genes (steroidogenic acute regulatory protein (Star), cytochrome P-450 (CYP11A1), CYP19A1, and steroidogenic factor 1 (SF-1)) and apoptosis-related genes (caspase-3, BCL-2, and BAX). Radio immunoassay (RIA) was used to analyze the level of 17beta-estradiol (E2) and progesterone (P4). We also assessed the apoptosis of GCs by flow cytometry. Our data suggested that heat stress induced GC apoptosis through the BAX/BCL-2 pathway and reduced the steroidogenic gene messenger RNA (mRNA) expression and E2 synthesis. These results suggest that the decreased function of GCs may cause ovarian dysfunction and offer an improved understanding of the molecular mechanism responsible for the low fertility in cattle in summer. PMID- 26847374 TI - Risk factors for Barrett's esophagus: a scoping review. AB - INTRODUCTION: Cancer of the esophagus is a highly lethal disease with many patients presenting with metastatic spread of their tumor at diagnosis; a consequence of this late presentation is the 5-year survival rate of <20 %. Barrett's esophagus (BE), a premalignant condition of the distal esophagus, is the main risk factor for adenocarcinoma of the esophagus. The development of a risk prediction tool that could assist healthcare professionals in identifying people at increased risk of developing BE would be advantageous. Understanding the factors that influence the risk of developing BE is the first stage of developing a risk prediction tool. METHODS: A scoping review was undertaken to address the following question 'what factors influence the risk of developing Barrett's esophagus?' Forty-six articles were included in this review. RESULTS: The majority of articles reviewed were case-control or cohort studies. Samples sizes ranged from 68 to 84,606. Risk factors reported to be statistically significant were divided into three categories: demographic, lifestyle and clinical factors. Strongest risk factors identified include: male gender, increasing age, white race, smoking, obesity and gastro-esophageal reflux disease symptoms, while some aspects of a person's diet appear to act as a protective measure. CONCLUSION: Risk factors for BE are complex and need to be considered by healthcare professionals when identifying patients that could benefit from endoscopic eradication. These results provide a stepping stone for the future development of a risk prediction model. PMID- 26847376 TI - ACMT Position Statement: Safety Issues Regarding Prescription Fentanyl Products. PMID- 26847377 TI - Improvements of deep vein reflux following radiofrequency ablation for saphenous vein incompetence. AB - Objectives The aim of this study was to describe the changes of deep vein reflux after radiofrequency ablation for great saphenous vein incompetence. Method The data on 139 limbs which were treated with radiofrequency ablation for great saphenous vein incompetence were prospectively collected and reviewed. Results Deep vein reflux was present in 43 of 139 limbs (30.9%). There were no significant differences in the rate of successful closure, the incidence of procedure-related complications, and the improvements of symptoms and quality of life between the limbs with or without deep vein reflux. With a mean follow-up of 5.9 months, the peak reflux velocity and duration of reflux were improved in all limbs with deep vein reflux and it was completely corrected in 13 limbs (30.2%) after radiofrequency ablation. Conclusions The presence of deep vein reflux does not affect the treatment outcomes of radiofrequency ablation for great saphenous vein incompetence and is improved in all patients. Deep vein reflux is not a barrier to performing radiofrequency ablation. PMID- 26847375 TI - Vulnerability of maize production under future climate change: possible adaptation strategies. AB - BACKGROUND: Climate change can affect the productivity and geographic distribution of crops. Therefore, evaluation of adaptive management options is crucial in dealing with negative impacts of climate change. The objectives of this study were to simulate the impacts of climate change on maize production in the north-east of Iran. Moreover, vulnerability index which indicated that how much of the crop yield loss is related to the drought was computed for each location to identify where adaptation and mitigation strategies are effective. Different sowing dates were also applied as an adaptation approach to decrease the negative impacts of climate change in study area. RESULTS: The results showed that the maize yield would decline during the 21st century from -2.6% to -82% at all study locations in comparison with the baseline. The result of vulnerability index also indicated that using the adaptation strategies could be effective in all of the study areas. Using different sowing dates as an adaptation approach showed that delaying the sowing date will be advantageous in order to obtain higher yield in all study locations in future. CONCLUSION: This study provided insight regarding the climate change impacts on maize production and the efficacy of adaptation strategies. (c) 2016 Society of Chemical Industry. PMID- 26847378 TI - HIV and Nurses: A Focus Group on Task Shifting in Uganda. AB - The HIV prevalence rate is 7.4% in Uganda, where the HIV-related President's Emergency Plan for AIDS Relief and United Nations millennial development goals have not been met. This is partially due to a critical shortage of nurses and other health care providers. Task shifting is a World Health Organization strategy to address the shortage of human resources for health by shifting work from one cadre of health care worker to another, often less-trained, cadre. We conducted three focus groups with nurses in Uganda to better understand perceptions of their preparation for and implementation of task shifting. The focus group included nurses from diverse work settings. Data analysis revealed that nurses were proud of the work they were doing but were challenged by the lack of consistent and appropriate support. We found a need for additional policies, regulations, and consistent preparation for nurses who work in environments with task shifting. PMID- 26847380 TI - A multi-level quantum mechanics and molecular mechanics study of SN2 reaction at nitrogen: NH2Cl + OH(-) in aqueous solution. AB - We employed a multi-level quantum mechanics and molecular mechanics approach to study the reaction NH2Cl + OH(-) in aqueous solution. The multi-level quantum method (including the DFT method with both the B3LYP and M06-2X exchange correlation functionals and the CCSD(T) method, and both methods with the aug-cc pVDZ basis set) was used to treat the quantum reaction region in different stages of the calculation in order to obtain an accurate potential of mean force. The obtained free energy activation barriers at the DFT/MM level of theory yielded a big difference of 21.8 kcal mol(-1) with the B3LYP functional and 27.4 kcal mol( 1) with the M06-2X functional respectively. Nonetheless, the barrier heights become very close when shifted from DFT to CCSD(T): 22.4 kcal mol(-1) and 22.9 kcal mol(-1) at CCSD(T)(B3LYP)/MM and CCSD(T)(M06-2X)/MM levels of theory, respectively. The free reaction energy obtained using CCSD(T)(M06-2X)/MM shows an excellent agreement with the one calculated using the available gas-phase data. Aqueous solution plays a significant role in shaping the reaction profile. In total, the water solution contributes 13.3 kcal mol(-1) and 14.6 kcal mol(-1) to the free energy barrier heights at CCSD(T)(B3LYP)/MM and CCSD(T)(M06-2X)/MM respectively. The title reaction at nitrogen is a faster reaction than the corresponding reaction at carbon, CH3Cl + OH(-). PMID- 26847381 TI - Two different mechanisms for the detection of stimulus omission. AB - Although we can detect slight changes in musical rhythm, the underlying neural mechanism remains elusive. Here we show that two distinct mechanisms are automatically selected depending on the speed of the rhythm. When human subjects detected a single omission of isochronous repetitive auditory stimuli, reaction time strongly depended on the stimulus onset asynchrony (SOA) for shorter SOAs (<250 ms), but was almost constant for longer SOAs. For shorter SOAs, subjects were unable to detect stimulus omission when either monaural stimuli or those in different frequencies were randomly presented. In contrast, for longer SOAs, reaction time increased when different tempos were presented simultaneously to different ears. These results suggest that depending on the speed of rhythms, the brain may use either temporal grouping of discrete sounds or temporal prediction of upcoming stimuli to detect the absence of a regular stimulus. Because we also found a similar relationship between reaction time and SOA for both visual and tactile stimuli, dual detection strategies could be generalized to other sensory modalities. PMID- 26847379 TI - Preliminary Findings Describing Participant Experience With iSTEP, an mHealth Intervention to Increase Physical Activity and Improve Neurocognitive Function in People Living With HIV. AB - We assessed the feasibility and acceptability of using text messages to monitor and encourage physical activity in the first 21 participants enrolled in an ongoing randomized controlled trial evaluating a 16-week Short Message Service/Multimedia Message Service (SMS/MMS) intervention (iSTEP) designed to increase moderate physical activity and improve neurocognition in persons with HIV-associated neurocognitive disorders (HAND; iSTEP, n = 11; control group, n = 10). Data were collected during the intervention and from interviews conducted at the 16-week postintervention visits. Text message response rates for both iSTEP and control participants were high (89% and 85%, respectively). Pedometer self monitoring, step count goals, and milestone achievement texts were reported to facilitate physical activity. All iSTEP participants (100%) and 70% of control participants indicated that they would recommend the study to other people living with HIV. The results indicate that it is feasible to administer an SMS/MMS physical activity intervention to persons with HAND. PMID- 26847382 TI - Time-dependent homeostasis between glucose uptake and consumption in astrocytes exposed to CoCl2 treatment. AB - Hypoxia has been implicated in the pathology of the central nervous system during stroke. It also has a significant effect on the regulation of glucose transporters (GLUTs), and homeostasis between glucose uptake and consumption. CoCl2 is a hypoxia-mimetic agent, and thus stabilizes the hypoxia-inducible factor 1alpha (HIF-1alpha) subunit and regulates GLUT genes. GLUT-1 and GLUT-3 are the most common isoforms of the GLUT family present in the brain, with the former primarily expressed in astrocytes and the latter in neurons under physiological conditions. However, it remains controversial whether GLUT-3 is expressed in astrocytes. Additionally, it is unclear whether the regulation of GLUT-1 and GLUT-3, and glucose homeostasis, are affected by CoCl2 treatment in a time-dependent manner. In the present study, mRNA and protein levels of GLUT-1, GLUT-3 and HIF-1alpha in astrocytes were examined by reverse transcription quantitative polymerase chain reaction and western blot analysis, respectively. The intracellular glucose concentration, glycogen storage, ATP content, pyruvate concentration, lactate dehydrogenase (LDH) release activity and cell viability in astrocytes were also investigated. The observations of the current study confirmed that both protein and mRNA levels of GLUT-1 and GLUT-3 were elevated in a time-dependent manner induced by CoCl2 treatment, followed by accumulation of HIF-1alpha. Furthermore, in the early period of CoCl2 treatment (<=8 h at 100 uM), LDH release, ATP content, glycogen storage and cell viability remained unchanged, whereas intracellular pyruvate concentration increased and glucose concentration was reduced. However, in the later period of CoCl2 treatment (>8 h at 100 uM), LDH release and intracellular pyruvate concentration increased, while intracellular glucose concentration, ATP content and glycogen storage were reduced. This may be due to disruption of homeostasis and reduced cell viability. In conclusion, alteration in the expression levels of GLUT-1 and GLUT-3, and the homeostasis between glucose uptake and consumption were affected by CoCl2 treatment, in a time-dependent manner, and may result in reduced energy production and cell viability in astrocytes. PMID- 26847383 TI - Charge-Induced Unzipping of Isolated Proteins to a Defined Secondary Structure. AB - Here we present a combined experimental and theoretical study on the secondary structure of isolated proteins as a function of charge state. In infrared spectra of the proteins ubiquitin and cytochrome c, amide I (C=O stretch) and amide II (N H bend) bands can be found at positions that are typical for condensed-phase proteins. For high charge states a new band appears, substantially red-shifted from the amide II band observed at lower charge states. The observations are interpreted in terms of Coulomb-driven transitions in secondary structures from mostly helical to extended C5 -type hydrogen-bonded structures. Support for this interpretation comes from simple energy considerations as well as from quantum chemical calculations on model peptides. This transition in secondary structure is most likely universal for isolated proteins that occur in mass spectrometric experiments. PMID- 26847385 TI - Complete cytogenetic response to Nilotinib in a chronic myeloid leukemia case with a rare e13a3(b2a3) BCR-ABL fusion transcript: A case report. AB - In the present study, an atypical case of chronic myeloid leukemia (CML) in a 32 year-old male was reported. CML cases with e13a3 breakpoint cluster region (BCR) ABL transcripts are extremely rare. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) was initially negative due to the primer corresponding to ABL a2 sequences and diagnosis was based upon analysis of the bone marrow smear, fluorescence in situ hybridization and karyotype analysis. RT-qPCR analysis with the ABL primer, which was located in ABL exon 3 to enable the detection of fusions with either ABL a2 or exon a3 demonstrated the presence of the BCR-ABL fusion transcript e13a3. The patient responded well to Nilotinib and achieved a complete cytogenetic response after 3 months. PMID- 26847384 TI - North Atlantic warming during Dansgaard-Oeschger events synchronous with Antarctic warming and out-of-phase with Greenland climate. AB - The precise reason for the differences and out-of-phase relationship between the abrupt Dansgaard-Oeschger warmings in the Nordic seas and Greenland ice cores and the gradual warmings in the south-central Atlantic and Antarctic ice cores is poorly understood. Termed the bipolar seesaw, the differences are apparently linked to perturbations in the ocean circulation pattern. Here we show that surface and intermediate-depth water south of Iceland warmed gradually synchronously with the Antarctic warming and out of phase with the abrupt warming of the Nordic seas and over Greenland. The hinge line between areas showing abrupt and gradual warming was close to the Greenland-Scotland Ridge and the marine system appears to be a 'push-and-pull' system rather than a seesaw system. 'Pull' during the warm interstadials, when convection in the Nordic seas was active; 'push' during the cold stadials, when convection stopped and warm water from the south-central Atlantic pushed northward gradually warming the North Atlantic and Nordic seas. PMID- 26847386 TI - 5-fluorouracil attenuates dextran sodium sulfate-induced acute colitis in mice. AB - 5-Fluorouracil (5-FU) has been predominantly used in the clinic for cancer chemotherapy. Previous studies have demonstrated that 5-FU has an anti inflammatory function. In the current study, the potential therapeutic role of 5 FU in dextran sodium sulfate (DSS)-induced acute mouse colitis was investigated. Effects on the severity of colitis were studied via histochemical and immunohistochemical staining, cytokine levels were determined by reverse transcriptoin-quantitative polymerase chain reaction and the effect of 5-FU on NF kappaB was examined by western blotting. Administration of 5-FU ameliorated the severity of acute DSS-induced colitis. The disease activity score was significantly lower in the 5-FU + DSS-treated mice compared with the DSS-treated group (P<0.01). Tumor necrosis factor-alpha, interleukin-1beta and interferon gamma mRNA expression levels were significantly downregulated in the colon tissue of DSS mice treated with 5-FU compared with the untreated DSS mice (P<0.05). In addition, the number of CD4+ T cells in the colonic lamina propria and myeloperoxidase activity were significantly decreased in the 5-FU + DSS-treated mice (P<0.05). Furthermore, 5-FU treatment significantly reduced p-NF-kappaB-p56 protein expression levels in the colon tissue of DSS-treated mice (P<0.05). The present results demonstrated that 5-FU minimizes the abnormal immune cytokine response and relieves the pathophysiological disorders associated with experimental acute colitis. Thus, the modulating inflammatory response role of 5 FU may be partially associated with inhibiting NF-kappaB activation and 5-FU may be a novel therapeutic strategy for the treatment of inflammatory bowel disease. PMID- 26847387 TI - Computer modeling of gastric parietal cell: significance of canalicular space, gland lumen, and variable canalicular [K+]. AB - A computer model, constructed for evaluation of integrated functioning of cellular components involved in acid secretion by the gastric parietal cell, has provided new interpretations of older experimental evidence, showing the functional significance of a canalicular space separated from a mucosal bath by a gland lumen and also shedding light on basolateral Cl(-) transport. The model shows 1) changes in levels of parietal cell secretion (with stimulation or H-K ATPase inhibitors) result mainly from changes in electrochemical driving forces for apical K(+) and Cl(-) efflux, as canalicular [K(+)] ([K(+)]can) increases or decreases with changes in apical H(+)/K(+) exchange rate; 2) H-K-ATPase inhibition in frog gastric mucosa would increase [K(+)]can similarly with low or high mucosal [K(+)], depolarizing apical membrane voltage similarly, so electrogenic H(+) pumping is not indicated by inhibition causing similar increase in transepithelial potential difference (Vt) with 4 and 80 mM mucosal K(+); 3) decreased H(+) secretion during strongly mucosal-positive voltage clamping is consistent with an electroneutral H-K-ATPase being inhibited by greatly decreased [K(+)]can (Michaelis-Menten mechanism); 4) slow initial change ("long time constant transient") in current or Vt with clamping of Vt or current involves slow change in [K(+)]can; 5) the Na(+)-K(+)-2Cl(-) symporter (NKCC) is likely to have a significant role in Cl(-) influx, despite evidence that it is not necessary for acid secretion; and 6) relative contributions of Cl(-)/HCO3 (-) exchanger (AE2) and NKCC to Cl(-) influx would differ greatly between resting and stimulated states, possibly explaining reported differences in physiological characteristics of stimulated open-circuit Cl(-) secretion (~H(+)) and resting short-circuit Cl(-) secretion (>>H(+)). PMID- 26847388 TI - Inositol for the prevention of neural tube defects: a pilot randomised controlled trial. AB - Although peri-conceptional folic acid (FA) supplementation can prevent a proportion of neural tube defects (NTD), there is increasing evidence that many NTD are FA non-responsive. The vitamin-like molecule inositol may offer a novel approach to preventing FA-non-responsive NTD. Inositol prevented NTD in a genetic mouse model, and was well tolerated by women in a small study of NTD recurrence. In the present study, we report the Prevention of Neural Tube Defects by Inositol (PONTI) pilot study designed to gain further experience of inositol usage in human pregnancy as a preliminary trial to a future large-scale controlled trial to evaluate efficacy of inositol in NTD prevention. Study subjects were UK women with a previous NTD pregnancy who planned to become pregnant again. Of 117 women who made contact, ninety-nine proved eligible and forty-seven agreed to be randomised (double-blind) to peri-conceptional supplementation with inositol plus FA or placebo plus FA. In total, thirty-three randomised pregnancies produced one NTD recurrence in the placebo plus FA group (n 19) and no recurrences in the inositol plus FA group (n 14). Of fifty-two women who declined randomisation, the peri-conceptional supplementation regimen and outcomes of twenty-two further pregnancies were documented. Two NTD recurred, both in women who took only FA in their next pregnancy. No adverse pregnancy events were associated with inositol supplementation. The findings of the PONTI pilot study encourage a large-scale controlled trial of inositol for NTD prevention, but indicate the need for a careful study design in view of the unwillingness of many high-risk women to be randomised. PMID- 26847389 TI - The potential benefit of allogeneic over autologous transplantation in patients with very early relapsed and refractory follicular lymphoma with prior remission duration of <=12 months. AB - Early relapsed or refractory follicular lymphoma (FL) warrants consolidation with transplantation, though graft source modality remains controversial. We analysed the outcomes of 44 patients transplanted with either autologous or allogeneic graft sources in the post-rituximab era. No difference in event-free (EFS) or overall survival (OS) was observed between allogeneic (81% and 81%) and autologous transplantation (64% and 70%) at 3 years. There was a significant difference in EFS between allogeneic and autologous transplantation patients with previous remission duration of <=12 months (80% and 42% at 3 years, P < 0.015). Very early relapsed FL may warrant consideration of allogeneic over autologous transplantation in the appropriate setting. PMID- 26847391 TI - Tooth loss and metabolic syndrome in middle-aged Japanese adults. AB - AIM: Metabolic syndrome is associated with periodontal disease and dental caries; however, little attention has been given to the association between metabolic syndrome and tooth loss, which is the endpoint of these two diseases. This study examined this association in middle-aged adults over a 5-year period. METHODS: A retrospective study was performed in 2107 participants (1718 males and 389 females) aged 35-60 years who underwent annual dental check-ups, to evaluate tooth loss and metabolic components, including obesity, elevated triglycerides, blood pressure, fasting glucose, and reduced high-density lipoprotein. Logistic regression analysis was performed to evaluate the association between metabolic syndrome (>=3 components) at the baseline examination and tooth loss. RESULTS: Over a 5-year period, 10.8% of the participants lost at least one tooth. Compared to those with no metabolic components, participants with >=3 components had an increased risk of tooth loss (odds ratio = 1.54; 95% confidence interval: 1.01 2.37), adjusting for age, gender, dental caries experience, attachment loss, oral hygiene status, number of teeth, tooth brushing frequency, smoking, and occupational status. CONCLUSIONS: Metabolic syndrome was associated with the incidence of tooth loss among middle-aged adults. PMID- 26847390 TI - Reprogramming of defended body weight after Roux-En-Y gastric bypass surgery in diet-induced obese mice. AB - OBJECTIVE: Roux-en-Y gastric bypass surgery (RYGB) results in sustained lowering of body weight in most patients, but the mechanisms involved are poorly understood. The aim of this study was to obtain support for the notion that reprogramming of defended body weight, rather than passive restriction of energy intake, is a fundamental mechanism of RYGB. METHODS: Male C57BL6J mice reaching different degrees of obesity on a high-fat diet either with ad libitum access or with caloric restriction (weight-reduced) were subjected to RYGB. RESULTS: RYGB induced weight loss and fat mass loss were proportional to pre-surgical levels, with moderately obese mice losing less body weight and fat compared with very obese mice. Remarkably, mice that were weight-reduced to the level of chow controls before surgery immediately gained weight after surgery, exclusively accounted for by lean mass gain. CONCLUSIONS: The results provide additional evidence for reprogramming of a new defended body weight as an important principle by which RYGB lastingly suppresses body weight. RYGB appears to selectively abolish defense of a higher fat mass level, while remaining sensitive to the defense of lean mass. The molecular and physiological mechanisms underlying this reprogramming remain to be elucidated. PMID- 26847392 TI - Tumour necrosis factor-alpha inhibitors for ankylosing spondylitis and non radiographic axial spondyloarthritis: a systematic review and economic evaluation. AB - BACKGROUND: Tumour necrosis factor (TNF)-alpha inhibitors (anti-TNFs) are typically used when the inflammatory rheumatologic diseases ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-AxSpA) have not responded adequately to conventional therapy. Current National Institute for Health and Care Excellence (NICE) guidance recommends treatment with adalimumab, etanercept and golimumab in adults with active (severe) AS only if certain criteria are fulfilled but it does not recommend infliximab for AS. Anti-TNFs for patients with nr-AxSpA have not previously been appraised by NICE. OBJECTIVE: To determine the clinical effectiveness, safety and cost-effectiveness within the NHS of adalimumab, certolizumab pegol, etanercept, golimumab and infliximab, within their licensed indications, for the treatment of severe active AS or severe nr-AxSpA (but with objective signs of inflammation). DESIGN: Systematic review and economic model. DATA SOURCES: Fifteen databases were searched for relevant studies in July 2014. REVIEW METHODS: Clinical effectiveness data from randomised controlled trials (RCTs) were synthesised using Bayesian network meta analysis methods. Results from other studies were summarised narratively. Only full economic evaluations that compared two or more options and considered both costs and consequences were included in the systematic review of cost effectiveness studies. The differences in the approaches and assumptions used across the studies, and also those in the manufacturer's submissions, were examined in order to explain any discrepancies in the findings and to identify key areas of uncertainty. A de novo decision model was developed with a generalised framework for evidence synthesis that pooled change in disease activity (BASDAI and BASDAI 50) and simultaneously synthesised information on function (BASFI) to determine the long-term quality-adjusted life-year and cost burden of the disease in the economic model. The decision model was developed in accordance with the NICE reference case. The model has a lifetime horizon (60 years) and considers costs from the perspective of the NHS and personal social services. Health effects were expressed in terms of quality-adjusted life-years. RESULTS: In total, 28 eligible RCTs were identified and 26 were placebo controlled (mostly up to 12 weeks); 17 extended into open-label active treatment only phases. Most RCTs were judged to have a low risk of bias overall. In both AS and nr-AxSpA populations, anti-TNFs produced clinically important benefits to patients in terms of improving function and reducing disease activity; for AS, the relative risks for ASAS 40 ranged from 2.53 to 3.42. The efficacy estimates were consistently slightly smaller for nr-AxSpA than for AS. Statistical (and clinical) heterogeneity was more apparent in the nr-AxSpA analyses than in the AS analyses; both the reliability of the nr-AxSpA meta-analysis results and their true relevance to patients seen in clinical practice are questionable. In AS, anti-TNFs are approximately equally effective. Effectiveness appears to be maintained over time, with around 50% of patients still responding at 2 years. Evidence for an effect of anti-TNFs delaying disease progression was limited; results from ongoing long-term studies should help to clarify this issue. Sequential treatment with anti-TNFs can be worthwhile but the drug survival response rates and benefits are reduced with second and third anti-TNFs. The de novo model, which addressed many of the issues of earlier evaluations, generated incremental cost-effectiveness ratios ranging from L19,240 to L66,529 depending on anti-TNF and modelling assumptions. CONCLUSIONS: In both AS and nr-AxSpA populations anti-TNFs are clinically effective, although more so in AS than in nr AxSpA. Anti-TNFs may be an effective use of NHS resources depending on which assumptions are considered appropriate. FUTURE WORK RECOMMENDATIONS: Randomised trials are needed to identify the nr-AxSpA population who will benefit the most from anti-TNFs. STUDY REGISTRATION: This study is registered as PROSPERO CRD42014010182. FUNDING: The National Institute for Health Research Health Technology Assessment programme. PMID- 26847393 TI - High expression of piwi-like RNA-mediated gene silencing 1 is associated with poor prognosis via regulating transforming growth factor-beta receptors and cyclin-dependent kinases in breast cancer. AB - Previous studies have demonstrated that abnormal expression levels of PIWI may serve a crucial role in tumorigenesis. However, the pathological role and its association with prognosis remains to be fully elucidated. In the present study, the expression levels of piwi-like RNA-mediated gene silencing 1 (HIWI) and piwi like RNA-mediated gene silencing 2 (HILI) in breast cancer tissues were reported to be high. The high expression levels of HIWI are correlated with poor prognosis in detected patients. In addition, by overexpression and interference, it was demonstrated that HIWI promotes the activity of breast cancer cells while depression of HIWI may induce apoptosis of breast cancer cells. It was additionally identified that suppression of HIWI may arrest the cells at the G2/M stage. The expression levels of transforming growth factor-beta receptor (TbetaR)I, TbetaRII, cyclin-dependent kinase (CDK)4, CDK6 and CDK8 were observed to be regulated by HIWI, which indicated a novel mechanism of HIWI in the regulation of breast cancer progression. The present study provides novel insight into the HIWI expression in breast cancer, providing a potential biomarker for assessment of prognosis and therapy of breast cancer. PMID- 26847394 TI - Influence of depth, time and human activity on detection rate of acoustic tags: a case study on two fish farms. AB - The detection rates of stationary acoustic transmitters deployed at three depths on two Atlantic salmon Salmo salar cage farms for c. 2 months were investigated. Deployment depth, time of day, day of the year and specific incidences at the farm substantially affected the rate of signal detection by the receiver. PMID- 26847395 TI - Total biosynthesis of opiates by stepwise fermentation using engineered Escherichia coli. AB - Opiates such as morphine and codeine are mainly obtained by extraction from opium poppies. Fermentative opiate production in microbes has also been investigated, and complete biosynthesis of opiates from a simple carbon source has recently been accomplished in yeast. Here we demonstrate that Escherichia coli serves as an efficient, robust and flexible platform for total opiate synthesis. Thebaine, the most important raw material in opioid preparations, is produced by stepwise culture of four engineered strains at yields of 2.1 mg l(-1) from glycerol, corresponding to a 300-fold increase from recently developed yeast systems. This improvement is presumably due to strong activity of enzymes related to thebaine synthesis from (R)-reticuline in E. coli. Furthermore, by adding two genes to the thebaine production system, we demonstrate the biosynthesis of hydrocodone, a clinically important opioid. Improvements in opiate production in this E. coli system represent a major step towards the development of alternative opiate production systems. PMID- 26847397 TI - Crosslinked Redox-Responsive Micelles Based on Lipoic Acid-Derived Amphiphiles for Enhanced siRNA Delivery. AB - Successful application of gene silencing approaches critically depends on systems that are able to safely and efficiently deliver genetic material such as small interfering RNA (siRNA). Due to their beneficial well-defined dendritic nanostructure, self-assembling dendrimers are emerging as promising nanovectors for siRNA delivery. However, these kinds of vectors are plagued with stability issues, especially when considered for in vivo applications. Therefore, in the present study, disulfide-based temporarily fixed micelles are developed that can degrade upon reductive conditions, and thus lead to efficient cargo release. In detail, lipoic acid-derived crosslinked micelles are synthesized based on small polymerizable dendritic amphiphiles. Particularly, one candidate out of this series is able to efficiently release siRNA due to its redox-responsive biodegradable profile when exposed to simulated intracellular environments. As a result, the reduction-triggered disassembly leads to potent gene silencing. In contrast, noncrosslinkable, structurally related constructs fails under the tested assay conditions, thereby confirming the applied rational design approach and demonstrating its large potential for future in vivo applications. PMID- 26847396 TI - Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates. AB - Traditional Chinese Medicines (TCMs) have been historically used to treat bacterial infections. However, the molecules responsible for these anti-infective properties and their potential mechanisms of action have remained elusive. Using a high-throughput assay for type III protein secretion in Salmonella enterica serovar Typhimurium, we discovered that several TCMs can attenuate this key virulence pathway without affecting bacterial growth. Among the active TCMs, we discovered that baicalein, a specific flavonoid from Scutellaria baicalensis, targets S. Typhimurium pathogenicity island-1 (SPI-1) type III secretion system (T3SS) effectors and translocases to inhibit bacterial invasion of epithelial cells. Structurally related flavonoids present in other TCMs, such as quercetin, also inactivated the SPI-1 T3SS and attenuated S. Typhimurium invasion. Our results demonstrate that specific plant metabolites from TCMs can directly interfere with key bacterial virulence pathways and reveal a previously unappreciated mechanism of action for anti-infective medicinal plants. PMID- 26847398 TI - The Betadine trial - antiseptic wound irrigation prior to skin closure at caesarean section to prevent surgical site infection: A randomised controlled trial. AB - BACKGROUND: Surgical site infections (SSIs) occur in around 10% of women following a caesarean section. Efforts to reduce SSI include wound irrigation with povidone-iodine (PVI), but studies are nonconclusive, mostly old and few on women having caesarean section (CS). AIMS: To assess povidone-iodine (PVI) (Betadine) irrigation of wound prior to skin closure in reducing incidence of SSI after CS. Our hypothesis was that there would be no benefit with its use in reducing SSIs. MATERIALS AND METHODS: A randomised controlled trial with 3027 women. Women having CS were allocated to receive PVI irrigation or no irrigation after closure of fascia and before skin closure. Women were followed up to four weeks to assess for SSI. Main outcome measure was surgical site infection. RESULTS: The two groups (1520 in Betadine and 1507 on no Betadine group) were well balanced. The incidence of SSI was similar in the two groups (9.5% vs 9.8%, RR 0.97; 95% CI 0.78-1.21). There was no difference between groups (2.6% vs 2.0%, RR 1.29, 95% CI 0.81-2.06 Betadine vs no Betadine, respectively) in readmission for wound infection requiring intravenous antibiotics; this was so in both the elective CS group as well as CS in labour group. CONCLUSION: PVI irrigation after the closure of fascia and before closure of skin is of no benefit in the prevention of SSI in women undergoing CS. PMID- 26847400 TI - 'A tract that is wholly sand:' engineering military environments in Libya. AB - In the late 1940s and early 1950s engineers from the U.S. Army Corps of Engineers constructed military facilities across newly independent Libya. This article examines how the local environment - namely the Sahara - shaped how these engineers planned for and carried out their assigned tasks. Though engineers initially hoped to apply experiences from the U.S. to things such as runway construction, they quickly learned that blowing sand, high temperatures and locust invasions could stymie their efforts. Engineers had to rethink what they thought they knew about things as mundane as concrete mixtures and wind-bearing loads. In doing so they created new networks of knowledge about building in hostile environments. Indeed, though long ignored in the scholarly literature on engineering, aviation and U.S. strategic deployments, the environment is everywhere in the documentary record about postwar military construction programs. This article, like the people it considers, takes the sand seriously. In doing so it also illuminates the surprisingly intimate ways that national security meets the everyday. PMID- 26847399 TI - Individualised distal femoral cut improves femoral component placement and limb alignment during total knee replacement in knees with moderate and severe varus deformity. AB - AIM: Our aim was to determine the variation in valgus correction angle and the influence of individualised distal femoral cut on femoral component placement and limb alignment during total knee replacement (TKR) in knees with varus deformity. MATERIALS AND METHODS: The study was done prospectively in two stages. In the first stage, the valgus correction angle (VCA) was calculated in long-limb radiographs of 227 patients and correlated with pre-operative parameters of femoral bowing, neck-shaft angle and hip-knee-ankle angle. In the second part comprising of 240 knees with varus deformity, 140 (group 1) had the distal femoral cut individualised according to the calculated VCA, while the remaining 100 knees (group 1) were operated with a fixed distal femoral cut of 5 degrees . The outcome of surgery was studied by grouping the knees as varus <10 degrees , 10-15 degrees and >15 degrees . RESULTS: Of the 227 limbs analysed in stage I, 70 knees (31 %) had a VCA angle outside 5-7 degrees . Coronal bowing (p < 0.001), neck-shaft angle (p < 0.001) and preoperative deformity (p < 0.001) significantly influenced VCA. Results of the second phase of the study showed a significant improvement in both femoral component placement and postoperative alignment when VCA was individualised in the groups of knees with varus 10-15 degrees (p 0.002) and varus >15 degrees (p 0.002). CONCLUSION: Valgus correction angle is highly variable and is influenced by femoral bowing, neck-shaft angle and pre-operative deformity. Individualisation of VCA is preferable in patients with moderate and severe varus deformity. LEVEL OF EVIDENCE: Level 2. PMID- 26847401 TI - Low incidence of anti-drug antibodies in patients with type 2 diabetes treated with once-weekly glucagon-like peptide-1 receptor agonist dulaglutide. AB - Therapeutic administration of peptides may result in anti-drug antibody (ADA) formation, hypersensitivity adverse events (AEs) and reduced efficacy. As a large peptide, the immunogenicity of once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist dulaglutide is of considerable interest. The present study assessed the incidence of treatment-emergent dulaglutide ADAs, hypersensitivity AEs, injection site reactions (ISRs), and glycaemic control in ADA-positive patients in nine phase II and phase III trials (dulaglutide, N = 4006; exenatide, N = 276; non-GLP-1 comparators, N = 1141). Treatment-emergent dulaglutide ADAs were detected using a solid-phase extraction acid dissociation binding assay. Neutralizing ADAs were detected using a cell-based assay derived from human endothelial kidney cells (HEK293). A total of 64 dulaglutide-treated patients (1.6% of the population) tested ADA-positive versus eight (0.7%) from the non-GLP 1 comparator group. Of these 64 patients, 34 (0.9%) had dulaglutide-neutralizing ADAs, 36 (0.9%) had native-sequence GLP-1 (nsGLP-1) cross-reactive ADAs and four (0.1%) had nsGLP-1 neutralization ADAs. The incidence of hypersensitivity AEs and ISRs was similar in the dulaglutide versus placebo groups. No dulaglutide ADA positive patient reported hypersensitivity AEs. Because of the low incidence of ADAs, it was not possible to establish their effect on glycaemic control. PMID- 26847402 TI - Oregon's Medicaid Coordinated Care Organizations. PMID- 26847403 TI - Profile of oxidative stress markers is dependent on vitamin D levels in patients with chronic hepatitis C. AB - OBJECTIVES: Although vitamin D deficiency can change liver injury progression in patients with hepatitis C virus (HCV), the main molecular mechanisms involved are largely unknown. The first aim of this study was to evaluate the association between oxidative stress and hypovitaminosis D in patients with HCV. The second aim was to verify whether oxidative stress is involved in the molecular mechanisms related to liver injury. METHODS: The study included 147 participants: 89 controls and 58 patients with HCV (vitamin D < 30, n = 32; vitamin D > 30, n = 26). RESULTS: Patients with HCV and hypovitaminosis D presented significantly higher aminotransferase-to-platelet ratio index (APRI; P = 0.0464) and viral load (P = 0.0426) levels than patients with HCV without hypovitaminosis D. Regarding oxidative stress, HCV patients with hypovitaminosis D had higher advanced oxidation protein products (P = 0.0409), nitric oxide metabolites (P = 0.0206) levels, and oxidative stress index (P = 0.0196), whereas total radical-trapping antioxidant parameter (P = 0.0446) levels were significantly lower than HCV patients without hypovitaminosis D. Vitamin D in patients with HCV showed inverse correlations with levels of iron (r = -0.407, P = 0.0285), ferritin (r = -0.383, P = 0.0444), APRI (r = -0.453, P = 0.0154) and plasma lipid hydroperoxides levels (r = -0.426, P = 0.0189). CONCLUSION: Vitamin D insufficiency contributes to the inflammatory process and oxidative stress imbalance in patients with HCV. The profile of oxidative stress markers in these patients depends on vitamin D levels, which probably change intracellular signalling pathways and increase inflammation and liver injury. PMID- 26847404 TI - Effect of SIRT1 Gene on Epithelial-Mesenchymal Transition of Human Prostate Cancer PC-3 Cells. AB - BACKGROUND The epithelial-mesenchymal transition (EMT) has been shown to be involved in the process of invasion and metastasis of prostate cancer. SIRT1 is the mammalian homologue of the silent information regulator 2 (Sir2) gene, and is abnormally expressed in prostate cancer cells. Therefore, it is hypothesized that SIRT1 mediates the invasion/metastatic ability of prostate cancer via EMT regulation. This study thus investigated the effect of SIRT1 gene on the invasion and migration of prostate cancer cell line PC-3 via the small interference RNA (siRNA) against SIRT1. MATERIAL AND METHODS SiRNA construct was transfected into PC-3 cells, which were tested for the cell migration and invasion ability by scratch assay and Transwell migration assay, respectively. Expression levels of vimentin, E-cadherin, and N-cadherin were further quantified by Western blotting and RT-PCR. RESULTS Both mRNA and protein levels of SIRT1 were depressed after siRNA transfection, along with weakened migration and invasion ability of PC-3 cells. Elevated E-cadherin and suppressed N-cadherin and vimentin were observed in those transfected cells. CONCLUSIONS The silencing of SIRT1 gene in PC-3 cells can suppress the movement, migration, and invasion functions of prostate cancer cells, possibly via the down-regulation of mesenchymal markers vimentin and N cadherin accompanied with up-regulation of epithelial marker N-cadherin, thus reversing the EMT process. PMID- 26847405 TI - What's in a line? Verbal, facial, and emotional influences on the line bisection task. AB - In Bryden and MacRae's [(1988). Dichotic laterality effects obtained with emotional words. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 1(3), 171-176] dichotic listening task, attending to verbal (left hemisphere) or emotional (right hemisphere) auditory stimuli can result in opposite patterns of behaviour. We examined whether performance on the line bisection task might also be influenced in opposite ways by left- and right-lateralized functions. The line bisection task is a simple and effective measure of visuospatial bias. Pseudoneglect, a leftward bias, is typically found on this task, and appears to result from right hemisphere dominance for spatial processing. We investigated how emotion, verbal, and facial processing impacted line bisection performance, while also examining the influence of hand-use. Line type (face, word, and solid), valence (positive, negative, and neutral), and hand-use (left, right, and both) were manipulated. Results indicated that face and word lines decreased and increased the extent of pseudoneglect, respectively, and that valence accentuated these results. These results were in the opposite direction from our predictions. Hand-use had little influence. We discuss the impact that visual scanning, and local and global processing, may have had on line bisection performance. Until future research clarifies how lateralized functions affect line bisections, we suggest caution in adapting the line bisection task as a general measure of relative hemispheric activation. PMID- 26847406 TI - Sensationalist Headlines: Also in the Scientific Press? Response by Abu-Assi et al. PMID- 26847407 TI - Glucose tolerance and cardiovascular risk biomarkers in non-diabetic non-obese obstructive sleep apnea patients: Effects of long-term continuous positive airway pressure. AB - BACKGROUND: Insulin resistance, glucose dyshomeostasis and oxidative stress are associated to the cardiovascular consequences of obstructive sleep apnea (OSA). The effects of a long-term continuous positive airway pressure (LT-CPAP) treatment on such mechanisms still remain conflicting. OBJECTIVE: To investigate the effect of LT-CPAP on glucose tolerance, insulin sensitivity, oxidative stress and cardiovascular biomarkers in non-obese non-diabetic OSA patients. PATIENTS & METHODS: Twenty-eight apneic, otherwise healthy, men suffering from OSA (mean age = 48.9 +/- 9.4 years; apnea-hypopnea index = 41.1 +/- 16.1 events/h; BMI = 26.6 +/- 2.8 kg/m(2); fasting glucose = 4.98 +/- 0.37 mmol/L) were evaluated before and after LT-CPAP by an oral glucose tolerance test (OGTT), measuring plasma glucose, insulin and proinsulin. Glycated hemoglobin, homeostasis model assessment resistance insulin, blood lipids, oxidative stress, homocysteine and NT-pro-brain natriuretic peptide (NT-proBNP) were also measured. RESULTS: LT-CPAP treatment lasted 13.9 +/- 6.5 months. At baseline, the time spent at SaO2<90%, minimal and mean SaO2 were associated with insulin area under the curve during OGTT (r = 0.448, P = 0.011; r = -0.382; P = 0.047 and r = -0.424; P = 0.028, respectively) and most other glucose/insulin homeostasis biomarkers, as well as with homocysteine (r = 0.531, P = 0.006; r = -0.487; P = 0.011 and r = -0.409; P = 0.034, respectively). LT-CPAP had no effect on all the OGTT-related measurements, but increased plasma total antioxidant status (+7.74%; P = 0.035) in a duration-dependent manner (r = 0.607; P < 0.001), and decreased both homocysteine (-15.2%; P = 0.002) and NT-proBNP levels (-39.3%; P = 0.002). CONCLUSIONS: In non-obese non-diabetic OSA patients, nocturnal oxygen desaturation is strongly associated to insulin resistance. LT-CPAP does not improve glucose homeostasis nor insulin sensitivity but has a favorable effect on antioxidant capacity and cardiovascular risk biomarkers. PMID- 26847408 TI - School environmental factors are predictive for exercise-induced symptoms in children. AB - BACKGROUND: Environmental factors in schools have a significant effect on the exercise-induced bronchoconstriction and symptoms in a general paediatric population. OBJECTIVES: To determine the environmental factors such as atmospheric conditions and the presence of allergens in gymnasiums, that could be predictive of the presence of exercise-induced symptoms/bronchospasm in children during physical education (PE). METHODS: 1370 schoolchildren were enrolled. Children attended 45 min PE lesson with similar exercise intensity. Pulmonary function tests were performed before and after PE lesson. Air temperature, humidity and pressure, samples of dust for allergen exposure in the gymnasiums were taken. Children who reported symptoms induced during PE lesson were invited to the clinic for ETC (exercise treadmill challenge) and atopy measurement. RESULTS: 1033 participants were included into the analysis. Sixty seven(6.5%) children reported dyspnea/cough, and in 94(9.4%) children bronchoconstriction induced during PE lesson was documented. There is a correlation between the results of the ETC and bronchoconstriction after PE (OR: 2.55; 95%CI: 1.07-6.05; p = 0.034). Exposure to higher air pressure and higher humidity independently increase the risk of clinical symptoms reported during or after PE lesson. Exposure to cat's allergens increase the risk of bronchoconstriction (independently from atopy status). We showed significant interaction between presence of asthma and current ICS therapy as a risk of physical inactivity at school (OR: 4; 95%CI: 1.3-12; p < 0.001). CONCLUSION: This study showed an effect of cat allergen and environmental factors (humidity, air pressure) on the appearance of exercise related cough/bronchoconstriction during activity class in a natural environment at school in a large urban population of schoolchildren. PMID- 26847409 TI - Dirac fermions at high-index surfaces of bismuth chalcogenide topological insulator nanostructures. AB - Binary bismuth chalcogenides Bi2Se3, Bi2Te3, and related materials are currently being extensively investigated as the reference topological insulators (TIs) due to their simple surface-state band dispersion (single Dirac cone) and relatively large bulk band gaps. Nanostructures of TIs are of particular interest as an increased surface-to-volume ratio enhances the contribution of surfaces states, meaning they are promising candidates for potential device applications. So far, the vast majority of research efforts have focused on the low-energy (0001) surfaces, which correspond to natural cleavage planes in these layered materials. However, the surfaces of low-dimensional nanostructures (nanoplatelets, nanowires, nanoribbons) inevitably involve higher-index facets. We perform a systematic ab initio investigation of the surfaces of bismuth chalcogenide TI nanostructures characterized by different crystallographic orientations, atomic structures and stoichiometric compositions. We find several stable terminations of high-index surfaces, which can be realized at different values of the chemical potential of one of the constituent elements. For the uniquely defined stoichiometric termination, the topological Dirac fermion states are shown to be strongly anisotropic with a clear dependence of Fermi velocities and spin polarization on the surface orientation. Self-doping effects and the presence of topologically trivial mid-gap states are found to characterize the non stoichiometric surfaces. The results of our study pave the way towards experimental control of topologically protected surface states in bismuth chalcogenide nanostructures. PMID- 26847410 TI - Correlation of volatile carbonyl yields emitted by e-cigarettes with the temperature of the heating coil and the perceived sensorial quality of the generated vapours. AB - E-liquids generally contain four main components: nicotine, flavours, water and carrier liquids. The carrier liquid dissolves flavours and nicotine and vaporises at a certain temperature on the atomizer of the e-cigarette. Propylene glycol and glycerol, the principal carriers used in e-liquids, undergo decomposition in contact with the atomizer heating-coil forming volatile carbonyls. Some of these, such as formaldehyde, acetaldehyde and acrolein, are of concern due to their adverse impact on human health when inhaled at sufficient concentrations. The aim of this study was to correlate the yield of volatile carbonyls emitted by e cigarettes with the temperature of the heating coil. For this purpose, a popular commercial e-liquid was machine-vaped on a third generation e-cigarette which allowed the variation of the output wattage (5-25W) and therefore the heat generated on the atomizer heating-coil. The temperature of the heating-coil was determined by infrared thermography and the vapour generated at each temperature underwent subjective sensorial quality evaluation by an experienced vaper. A steep increase in the generated carbonyls was observed when applying a battery output of at least 15W corresponding to 200-250 degrees C on the heating coil. However, when considering concentrations in each inhaled puff, the short-term indoor air guideline value for formaldehyde was already exceeded at the lowest wattage of 5W, which is the wattage applied in most 2nd generation e-cigarettes. Concentrations of acetaldehyde in each puff were several times below the short term irritation threshold value for humans. Acrolein was only detected from 20W upwards. The negative sensorial quality evaluation by the volunteering vaper of the vapour generated at 20W demonstrated the unlikelihood that such a wattage would be realistically set by a vaper. This study highlights the importance to develop standardised testing methods for the assessment of carbonyl-emissions and emissions of other potentially harmful compounds from e-cigarettes. The wide variety and variability of products available on the market make the development of such methods and the associated standardised testing conditions particularly demanding. PMID- 26847411 TI - Air pollution and depressed mood: Consistency of association. PMID- 26847412 TI - Studies on prevalence of biofilm associated genes and primary observation on sasX gene in clinical isolates of coagulase negative staphylococci (CoNS). AB - Coagulase negative staphylococci (CoNS) are nosocomial pathogens that cause indwelling medical device associated infections due to its biofilm forming potential and multiple antibiotic resistance. The current study focused on species identification, antibiotic resistance profile and molecular basis of biofilm formation and attachment of CoNS isolated from clinical samples. Along with this, molecular screening for mecA and newly identified surface colonization protein encoded by sasX gene was also conducted. S. epidermidis (n = 19, 47%) was identified as the most prevalent CoNS species and very interestingly two biofilm forming, mecA positive S. epidermidis isolates were found to carry all the biofilm associated genes screened in this study, which indicates its potential to form the strong biofilm. Another novel observation of the study is the detection of sasX gene in one biofilm positive S. epidermidis isolate. The study also identified one doxycycline resistant mecA positive, multidrug resistant S. haemolyticus isolate. In conclusion, the study signifies the existence of multiple biofilm related genes, multidrug resistance and the presence of sasX gene among clinical isolates of CoNS. PMID- 26847413 TI - Ultrasound Imaging of the Musculoskeletal System. AB - Musculoskeletal ultrasound is a rapidly growing field within veterinary medicine. Ultrasound for musculoskeletal disorders has been commonly used in equine and human medicine and is becoming more commonly performed in small animal patients due to the increase in the recognition of soft tissue injuries. Ultrasound is widely available, cost-effective, but technically difficult to learn. Advantages of musculoskeletal ultrasound are the opposite limb is commonly used for comparison to evaluate symmetry of the tendinous structures and the ease of repeat examinations to assess healing. The article discusses the major areas of shoulder, stifle, iliopsoas, gastrocnemius, and musculoskeletal basics. PMID- 26847414 TI - Amino acid changes in PB2 and HA affect the growth of a recombinant influenza virus expressing a fluorescent reporter protein. AB - Influenza viruses that express reporter proteins are useful tools, but are often attenuated. Recently, we found that an influenza virus encoding the Venus fluorescent protein acquired two mutations in its PB2 and HA proteins upon mouse adaptation. Here, we demonstrate that the enhanced viral replication and virulence in mice of this Venus-expressing influenza virus are primarily conferred by the PB2-E712D mutation, with only a minor contribution by the HA T380A mutation. PMID- 26847415 TI - Ouro proteins are not essential to tail regression during Xenopus tropicalis metamorphosis. AB - Tail regression is one of the most prominent transformations observed during anuran metamorphosis. A tadpole tail that is twice as long as the tadpole trunk nearly disappears within 3 days in Xenopus tropicalis. Several years ago, it was proposed that this phenomenon is driven by an immunological rejection of larval skin-specific antigens, Ouro proteins. We generated ouro-knockout tadpoles using the TALEN method to reexamine this immunological rejection model. Both the ouro1- and ouro2-knockout tadpoles expressed a very low level of mRNA transcribed from a targeted ouro gene, an undetectable level of Ouro protein encoded by a target gene and a scarcely detectable level of the other Ouro protein from the untargeted ouro gene in tail skin. Furthermore, congenital athymic frogs were produced by Foxn1 gene modification. Flow cytometry analysis showed that mutant frogs lacked splenic CD8(+) T cells, which play a major role in cytotoxic reaction. Furthermore, T-cell-dependent skin allograft rejection was dramatically impaired in mutant frogs. None of the knockout tadpoles showed any significant delay in the process of tail shortening during the climax of metamorphosis, which shows that Ouro proteins are not essential to tail regression at least in Xenopus tropicalis and argues against the immunological rejection model. PMID- 26847416 TI - Dietary Total Antioxidant Capacity is Inversely Associated with Prostate Cancer Aggressiveness in a Population-Based Study. AB - The purpose of this study was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina-Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire. EA reported greater dietary TAC from diet and supplements combined (P < 0.0001). In both minimally and fully adjusted logistic regression models, TAC from diet and supplements combined was associated with a reduced odds of high aggressive prostate cancer in all men, AA and EA: odds ratios for highest vs. lowest level (>1500 vs. <500 mg vitamin C equivalent/day): 0.31 [95% confidence interval (CI): 0.15, 0.67; P trend < 0.01], 0.28 (95% CI: 0.08, 0.96; P-trend < 0.001), and 0.36 (95% CI: 0.15, 0.86; P-trend = 0.58), respectively. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer. Additional research is needed to confirm these results and determine the underlying mechanisms. PMID- 26847417 TI - Time trends in upper gastrointestinal diseases and Helicobacter pylori infection in a multiracial Asian population--a 20-year experience over three time periods. AB - BACKGROUND: Marked epidemiological changes in upper gastrointestinal diseases and Helicobacter pylori infection have taken place in the Asian Pacific region. In particular, differences with respect to race in the multiracial Asian population in Malaysia have been important and interesting. AIM: A time trend study of upper gastrointestinal disease and H. pylori infection in three time periods: 1989 1990, 1999-2000 and 2009-2010 spanning a period of 20 years was carried out. METHODS: Consecutive first time gastroscopies carried out on patients attending the University of Malaya Medical Center were studied. Diagnoses and H. pylori infection status were carefully recorded. RESULTS: A steady decline in prevalence of duodenal ulcer (DU) and gastric ulcer (GU) from 21.1% to 9.5% to 5.0% and from 11.9% to 9.4% to 9.9% while an increase in erosive oesophagitis (EO) from 2.0% to 8.4% to 9.5% (chi-square for trend; P < 0.001) for the periods 1989-1990, 1999 200 and 2009-2010 were observed. The overall prevalence of H. pylori had also decreased from 51.7% to 30.3% to 11.1% for the same periods of time. The proportion of H. pylori positive ulcers had also decreased: DU (90.1%-69.8% 28.9%) and GU (86.6-56.8%-18.9%) (P < 0.001). This was observed in Malays, Chinese and Indians but the difference over time was most marked in Malays. There was a steady decline in the proportion of patients with gastric and oesophageal cancers. CONCLUSIONS: Peptic ulcers have declined significantly over a 20-year period together with a decline in H. pylori infection. In contrast, a steady increase in erosive oesophagitis was observed. Gastric and oesophageal squamous cell cancers have declined to low levels. PMID- 26847418 TI - HMGB1, S100 proteins and other RAGE ligands in cancer - markers, mediators and putative therapeutic targets. AB - BACKGROUND AND AIMS: Activation of RAGE due to its increased expression in cancer cells or its stimulation by multiple ligands (AGEs, HMGB1, S100 proteins, etc.) may contribute to the proliferation, invasiveness of tumor cells and formation of distant metastases and also to the resistance of cancer to treatment. RAGE ligands could thus become both useful markers of disease severity and its outcome and, a potential therapeutic target. CONCLUSIONS: Better understanding of the role of RAGE activation in different types of cancer may help to define the role of ligand/RAGE antagonists as promising cancer treatment. PMID- 26847419 TI - New hybrid procedures in treating occluded arteriovenous hemodialysis grafts. AB - BACKROUND: The use of arteriovenous graft is indicated in patients if the subcutaneous venous bed is exhausted or unsuitable for arteriovenous fistula creation. The leading cause of failure of a prosthetic arteriovenous hemodialysis access graft is venous anastomotic stenosis causing thrombosis of the graft. A number of surgical techniques and endovascular tools have been used to treat this stenosis and thrombosis. None have yet proven to be ideal. This study was designed to evaluate the results of hybrid treatment of arteriovenous graft thrombosis associated with venous anastomotic stenosis. METHODS: Over the period 2013-2014, we treated 16 AVG occlusions. Immediately after the diagnosis of occlusion was made, the patients underwent thrombectomy using a Fogarty catheter. After thrombectomy, a diagnostic fistulogram was performed and if VAG stenosis was confirmed, it was treated with balloon angioplasty and stent graft introduction. Lesions were dilated to reduce the stenosis in the treated area to less than 25%. RESULTS: Primary patency after 12 months was 32.8%. Primary assisted patency was 44.7%, secondary patency was 47.6%. Restenosis of the stent graft was seen in two patients. Recurring AVG occlusion was observed in four patients. The average number of interventions to maintain AVG patency was 1.18 per patient/1 year of dialysis. CONCLUSION: Treatment of AVG thrombosis due to VAG stenosis by hybrid procedure proved to be effective and improved secondary patency. PMID- 26847420 TI - Autism genetic testing information needs among parents of affected children: A qualitative study. AB - OBJECTIVE: Leading health agencies recommend physicians to provide information regarding genetic testing for autism spectrum disorders (ASD) to parents of affected children. How to effectively provide this information, however, is unclear for physicians. This qualitative study examined the information needs regarding ASD genetic testing among parents of affected children. METHODS: Semi structured, in-depth interviews were conducted with 42 parents who had at least one child with ASD. Content analysis was utilized to analyze the interview data. RESULTS: The majority of parents (83%) reported they had never received information regarding ASD genetic testing from their doctors. Nevertheless, most parents (86%) expressed an interest to learn about this information. Their preferred topics included: cost (60%), benefits (48%), accuracy (38%), test procedure (29%), potential physical harms from the test (29%), confidentiality (12%), previous utilization by other affected families (2%), and eligibility criteria for this genetic testing (2%). Moreover, parents mentioned various methods to facilitate their learning, including Web-based approaches (43%), workshops/seminars (36%), brochures and flyers (31%), and videos (10%). CONCLUSION: To promote parental informed decision-making regarding ASD genetic testing, educational materials should be developed based on our findings. PRACTICE IMPLICATIONS: Application of these needs assessment findings will subsequently improve the delivery of healthcare services. PMID- 26847423 TI - Bilateral Foot Gangrene. PMID- 26847421 TI - Between-race differences in the effects of breast density information and information about new imaging technology on breast-health decision-making. AB - OBJECTIVES: Some US states have mandated that women be informed when they have dense breasts; however, little is known about how general knowledge about breast density (BD) affects related health decision-making. We examined the effects of BD information and imaging technology information on 138 African-American (AA) and European-American (EA) women's intentions to discuss breast cancer screening with their physicians. METHODS: Women were randomly assigned to receive BD information and/or imaging technology information via 2 by 2 factorial design, and completed planned behavior measures (e.g., attitudes, intentions) related to BC screening. RESULTS: Attitudes mediated the effects of BD information, and the mediation was stronger for AA women compared to EA women. Effects were more robust for BD information compared to imaging technology information. Results of moderator analyses revealed suppressor effects of injunctive norms that were moderated by imaging technology information. CONCLUSION: Information about BD favorably influences women's intentions to engage in relevant breast health behaviors. Stronger attitude mediated-effects for AA women suggest greater scrutiny of BD information. PRACTICE IMPLICATIONS: Since BD information may influence women's intentions to discuss BC screening, strategies to effectively present BD information to AA women should be investigated given the likelihood of their increased scrutiny of BD information. PMID- 26847422 TI - Differential DNA methylation in peripheral blood mononuclear cells in adolescents exposed to significant early but not later childhood adversity. AB - Internationally adopted adolescents who are adopted as young children from conditions of poverty and deprivation have poorer physical and mental health outcomes than do adolescents conceived, born, and raised in the United States by families similar to those who adopt internationally. Using a sample of Russian and Eastern European adoptees to control for Caucasian race and US birth, and nonadopted offspring of well-educated and well-resourced parents to control for postadoption conditions, we hypothesized that the important differences in environments, conception to adoption, might be reflected in epigenetic patterns between groups, specifically in DNA methylation. Thus, we conducted an epigenome wide association study to compare DNA methylation profiles at approximately 416,000 individual CpG loci from peripheral blood mononuclear cells of 50 adopted youth and 33 nonadopted youth. Adopted youth averaged 22 months at adoption, and both groups averaged 15 years at testing; thus, roughly 80% of their lives were lived in similar circumstances. Although concurrent physical health did not differ, cell-type composition predicted using the DNA methylation data revealed a striking difference in the white blood cell-type composition of the adopted and nonadopted youth. After correcting for cell type and removing invariant probes, 30 CpG sites in 19 genes were more methylated in the adopted group. We also used an exploratory functional analysis that revealed that 223 gene ontology terms, clustered in neural and developmental categories, were significantly enriched between groups. PMID- 26847424 TI - Parental Involvement and Adolescents' Educational Success: The Roles of Prior Achievement and Socioeconomic Status. AB - Parental educational involvement in primary and secondary school is strongly linked to students' academic success; however; less is known about the long-term effects of parental involvement. In this study, we investigated the associations between four aspects of parents' educational involvement (i.e., home- and school based involvement, educational expectations, academic advice) and young people's proximal (i.e., grades) and distal academic outcomes (i.e., educational attainment). Attention was also placed on whether these relations varied as a function of family socioeconomic status or adolescents' prior achievement. The data were drawn from 15,240 10th grade students (50 % females; 57 % White, 13 % African American, 15 % Latino, 9 % Asian American, and 6 % other race/ethnicity) participating in the Education Longitudinal Study of 2002. We observed significant links between both school-based involvement and parental educational expectations and adolescents' cumulative high school grades and educational attainment. Moderation analyses revealed that school-based involvement seemed to be particularly beneficial for more disadvantaged youth (i.e., those from low-SES families, those with poorer prior achievement), whereas parents' academic socialization seemed to better promote the academic success of more advantaged youth (i.e., those from high-SES families, those with higher prior achievement). These findings suggest that academic interventions and supports could be carefully targeted to better support the educational success of all young people. PMID- 26847425 TI - Complementary role of magnetic resonance imaging in the study of the fetal urinary system. AB - Urinary system birth defects represent the abnormality most often detected in prenatal studies, accounting for 30% to 50% of all structural anomalies present at birth. The most common disorders are urinary tract dilation, developmental variants, cystic kidney diseases, kidney tumors, and bladder defects. These anomalies can present in isolation or in association with various syndromes. They are normally evaluated with sonography, and the use of magnetic resonance imaging (MRI) is considered only in inconclusive cases. In this article, we show the potential of fetal MRI as a technique to complement sonography in the study of fetal urinary system anomalies. We show the additional information that MRI can provide in each entity, especially in the evaluation of kidney function through diffusion-weighted sequences. PMID- 26847426 TI - Downregulation of thymidylate synthase by RNAi molecules enhances the antitumor effect of pemetrexed in an orthotopic malignant mesothelioma xenograft mouse model. AB - Malignant pleural mesothelioma (MPM) is an incurable cancer with an increasing incidence. Currently, pemetrexed (PMX)-based chemotherapy is the mainstay of chemotherapy for MPM, however, the outcome of PMX-based chemotherapy in patients with MPM is dismal. RNA interference (RNAi) technology has been considered as an effective tool to substantially enhance the therapeutic efficacy of chemotherapeutic agents in many preclinical and clinical settings. In this study, therefore, we investigated whether non-viral anti-thymidylate synthase RNAi embedded liposome (TS shRNA lipoplex) would effectively guide the downregulation of TS in human malignant mesothelioma MSTO-211H cells. Consequently, it enhanced the antitumor effect of PMX both in vitro and in vivo. TS shRNA effectively enhanced the in vitro cell growth inhibition upon treatment with PMX via downregulating TS expression in the MSTO-211H cell line. In in vivo orthotopic tumor model, the combined treatment of PMX and TS shRNA lipoplex efficiently combated the progression of orthotopic thoracic tumors and as a result prolonged mouse survival, compared to each single treatment. Our findings emphasize the pivotal relevance of RNAi as an effective tool for increasing the therapeutic efficacy of PMX, a cornerstone in the treatment regimens of MPM, and thereby, raising the possibility for the development of a novel therapeutic strategy, combination therapy of TS-shRNA and PMX, that can surpass many of the currently applied, but less effective, therapeutic regimens against lethal MPM. PMID- 26847427 TI - Dramatic enhancement of supercontinuum generation in elliptically-polarized laser filaments. AB - Broadband laser sources based on supercontinuum generation in femtosecond laser filamentation have enabled applications from stand-off sensing and spectroscopy to the generation and self-compression of high-energy few-cycle pulses. Filamentation relies on the dynamic balance between self-focusing and plasma defocusing - mediated by the Kerr nonlinearity and multiphoton or tunnel ionization, respectively. The filament properties, including the supercontinuum generation, are therefore highly sensitive to the properties of both the laser source and the propagation medium. Here, we report the anomalous spectral broadening of the supercontinuum for filamentation in molecular gases, which is observed for specific elliptical polarization states of the input laser pulse. The resulting spectrum is accompanied by a modification of the supercontinuum polarization state and a lengthening of the filament plasma column. Our experimental results and accompanying simulations suggest that rotational dynamics of diatomic molecules play an essential role in filamentation-induced supercontinuum generation, which can be controlled with polarization ellipticity. PMID- 26847428 TI - Do internationally adopted children in the Netherlands use more medication than their non-adopted peers? AB - Empirical evidence has shown that international adoptees present physical growth delays, precocious puberty, behavioral problems, and mental health referrals more often than non-adoptees. We hypothesized that the higher prevalence of (mental) health problems in adoptees is accompanied by elevated consumption of prescription drugs, including antidepressants, attention deficit hyperactivity disorder (ADHD) medication, and medication for growth inhibition/stimulation. In an archival, population-based Dutch cohort study, data on medication use were available from the Health Care Insurance Board by Statistics Netherlands from 2006 to 2011. The Dutch population born between 1994 and 2005 and alive during the period of measurement was included (2,360,450 including 10,602 international adoptees, of which 4447 from China). Their mean age was 6.5 years at start (range 1-12 years) and 11.5 years at the end of the measurement period (range 6-17 years). Chinese female adoptees used less medication for precocious puberty (as treatment for precocious puberty; odds ratio (OR) = 0.57, effect size Cohen's d = -0.31) and contraception (OR = 0.65, d = -0.24) than non-adoptees. For both males and females, non-Chinese adoptees used more medication for ADHD than non-adoptees (males: OR = 1.22, females: OR = 1.32), but the effect was small (males: d = 0.11, females: d = 0.15). CONCLUSIONS: Adoptees in the Netherlands generally do not use more medication than their non-adopted peers. WHAT IS KNOWN: * Meta analytical evidence shows that international adoptees present physical growth delays and mental health referrals more often than non-adopted controls. * With the exception of one Swedish study on ADHD medication, there is no other systematic research on medication use of international adoptees. What is New: * All differences in medication use between international adoptees in the Netherlands and non-adopted controls were below the threshold of a small effect with the exception of medication for precocious puberty, but this effect was in the opposite direction with female adoptees using less medication for precocious puberty than non-adoptees. * International adoptees in the Netherlands do not use more medication despite experiences of preadoption adversity and higher rates of mental health referrals during childhood and adolescence. PMID- 26847429 TI - The long-term treatment of a patient with type 1 diabetes mellitus and glutaric aciduria type 1: the effect of insulin. AB - The coexistence of two diseases associated with different metabolic disorders is a very rare event. Some associations, although sporadic, can be particularly challenging both in terms of diagnostic and therapeutic management and in terms of theoretical perspective. Here, we report a child affected by type 1 diabetes mellitus (T1DM) and glutaric aciduria type 1 (GA1). The child was diagnosed with classical T1DM at 15 months of age, with a tendency toward hypoglycemia. A few months later, during an acute intercurrent infective episode, the child displayed acute hypotonia of the lower limbs and limbs dystonia. A brain MRI showed bilateral striatal necrosis, suggesting GA1 diagnosis. Treatment with a low lysine dietary regimen and carnitine supplementation was started and resulted in an improvement in metabolic control and a reduction of hypoglycemic episodes along with an increasing in insulin daily dose. After 2 years, the neurological outcome consisted of a reduction in dystonic movements and a metabolic stability of both diseases. CONCLUSION: This case provides some insight into the reciprocal interconnections between the two metabolic disorders. Similar pathogenic mechanisms responsible for the neuronal injury might have impacted each other, and a strict relationship between a specific aspect of GA1-impaired metabolism and glucose homeostasis might explain how the tailored management of GA1 was not only effective in controlling the disease, but it also resulted in an improvement in the control of the glycemic profile. What in known: * Glutaric aciduria type 1 (GA1) usually presents in childhood with severe and possibly irreversible neuronal damage, triggered by a catabolic stress * The association of GA1 with other diseases, including type 1 diabetes mellitus (T1DM), is a rare event, complicating the treatment management What is new: * Insulin treatment has a role in preventing GA1 metabolic decompensation, even in the catabolic condition of hypoglycemia * Promoting GA1 metabolic equilibrium by tailoring drug and dietary treatment in our patient affect by T1DM has a positive impact also in improving glycemic balance. PMID- 26847430 TI - An innovative pedagogic course combining video and simulation to teach medical students about pediatric cardiopulmonary arrest: a prospective controlled study. AB - Compliance by residents in pediatrics to pediatric resuscitation guidelines is low. In many French faculties, a 1-h traditional lecture is still used to educate medical students about pediatric cardiopulmonary arrest (CPA). We developed an innovative pedagogic course combining a 23-min video and 3-h simulation exercises to improve knowledge and skills of medical students. A prospective controlled study was conducted. Medical student knowledge was tested before, just after, and 6-12 months after the innovative course and compared to that of a cohort who attended the traditional lecture. A high-fidelity mannequin simulator simulating cardiopulmonary arrest was used to assess and compare the skills of the study and control groups. Costs of the courses were evaluated; 809 of 860 (94 %) medical students were assessed for knowledge. Six to 12 months after the courses, the median score was significantly higher for the innovative group than that for the traditional lecture group (p < 0.001). In terms of skills, student in the innovative group scored higher on the performance score than the control group (p < 0.01). The innovative course was 24 times more expensive. CONCLUSION: Combination of video and simulation allows better retention of knowledge than a traditional lecture and leads to better compliance to resuscitation guidelines. WHAT IS KNOWN: * Compliance by residents to pediatric resuscitation guidelines is low. * We developed an innovative pedagogic course combining an educational video and simulation. What is new: * Knowledge retention after the innovative course was better than after a traditional lecture. * Sixty-six students tested on their skills demonstrated better compliance to resuscitation guidelines. PMID- 26847431 TI - Platelet Factor 4 Inhibits and Enhances HIV-1 Infection in a Concentration Dependent Manner by Modulating Viral Attachment. AB - Platelet factor 4 (PF4) has been recently shown to inhibit infection by a broad range of human immunodeficiency virus type 1 (HIV-1) isolates in vitro. We found that the inhibitory effects of PF4 are limited to a defined concentration range where PF4 exists largely in a monomeric state. Under these conditions, PF4 bound the HIV-1 envelope protein and inhibited HIV-1 attachment to the cell surface. However, as concentrations increased to the point where PF4 exists largely in tetrameric or higher-order forms, viral infection in vitro was enhanced. Enhancement could be inhibited by mutations in PF4 that shift the oligomeric equilibrium toward the monomeric state, or by using soluble glycosaminoglycans (GAGs) to which tetrameric PF4 avidly binds. We conclude that at physiologically relevant concentrations, oligomeric PF4 enhances infection by HIV-1 by interacting with the viral envelope protein as well as cell surface GAGs, enhancing virus attachment to the cell surface. This effect was not specific to HIV-1, as enhancement was seen with some but not all other viruses tested. The biphasic effects of PF4 on HIV-1 infection suggest that native PF4 will not be a useful antiviral agent and that PF4 could contribute to the hematologic abnormalities commonly seen in HIV-infected individuals by enhancing virus infection in the bone marrow. PMID- 26847432 TI - Using systematic reviews for hazard and risk assessment of endocrine disrupting chemicals. AB - The possibility that endocrine disrupting chemicals (EDCs) in our environment contribute to hormonally related effects and diseases observed in human and wildlife populations has caused concern among decision makers and researchers alike. EDCs challenge principles traditionally applied in chemical risk assessment and the identification and assessment of these compounds has been a much debated topic during the last decade. State of the science reports and risk assessments of potential EDCs have been criticized for not using systematic and transparent approaches in the evaluation of evidence. In the fields of medicine and health care, systematic review methodologies have been developed and used to enable objectivity and transparency in the evaluation of scientific evidence for decision making. Lately, such approaches have also been promoted for use in the environmental health sciences and risk assessment of chemicals. Systematic review approaches could provide a tool for improving the evaluation of evidence for decision making regarding EDCs, e.g. by enabling systematic and transparent use of academic research data in this process. In this review we discuss the advantages and challenges of applying systematic review methodology in the identification and assessment of EDCs. PMID- 26847434 TI - Parathyroid Hormone (1-34) Transiently Protects Against Radiation-Induced Bone Fragility. AB - Radiation therapy for soft tissue sarcoma or tumor metastases is frequently associated with damage to the underlying bone. Using a mouse model of limited field hindlimb irradiation, we assessed the ability of parathyroid hormone (1-34) fragment (PTH) delivery to prevent radiation-associated bone damage, including loss of mechanical strength, trabecular architecture, cortical bone volume, and mineral density. Female BALB/cJ mice received four consecutive doses of 5 Gy to a single hindlimb, accompanied by daily injections of either PTH or saline (vehicle) for 8 weeks, and were followed for 26 weeks. Treatment with PTH maintained the mechanical strength of irradiated femurs in axial compression for the first eight weeks of the study, and the apparent strength of irradiated femurs in PTH-treated mice was greater than that of naive bones during this time. PTH similarly protected against radiation-accelerated resorption of trabecular bone and transient decrease in mid-diaphyseal cortical bone volume, although this benefit was maintained only for the duration of PTH delivery. Overall, PTH conferred protection against radiation-induced fragility and morphologic changes by increasing the quantity of bone, but only during the period of administration. Following cessation of PTH delivery, bone strength and trabecular volume fraction rapidly decreased. These data suggest that PTH does not negate the longer-term potential for osteoclastic bone resorption, and therefore, finite-duration treatment with PTH alone may not be sufficient to prevent late onset radiotherapy induced bone fragility. PMID- 26847435 TI - Rationale for Strengthening Muscle to Prevent Falls and Fractures: A Review of the Evidence. AB - Falls represent a major public health problem in older people, predominantly due to the resulting injuries which lead to progressive disability, immobilization and resulting comorbidities, dependency, institutionalization, and death. Reduced muscle strength and power have been consistently identified as risk factors for falls and related injuries, and it is likely these associations result from the central role played by reduced muscle strength and power in poor balance recovery. In addition, muscle strength and power are involved with protective responses that reduce the risk of an injury if a fall occurs. Progressive resistance training (PRT) is the standard way to increase muscle strength and power, and this training forms one of the main components of fall prevention exercise interventions. However, PRT has rarely been implemented in routine practice due to multiple challenges inherent to frail older people. The ongoing development of drugs expected to increase muscle power offers a new opportunity to reduce the risk of falls and fall-related injuries. The intent here is not to replace exercise training with drugs but rather to offer a pharmacologic alternative when exercise is not possible or contraindicated. The target population would be those most likely to benefit from this mechanism of action, i.e., weak older people without major causes for falls independent of muscle weakness. Provided such a tailored strategy was followed, a muscle anabolic may address this major unmet need. PMID- 26847436 TI - Respiratory mechanics and lung stress/strain in children with acute respiratory distress syndrome. AB - BACKGROUND: In sedated and paralyzed children with acute respiratory failure, the compliance of respiratory system and functional residual capacity were significantly reduced compared with healthy subjects. However, no major studies in children with ARDS have investigated the role of different levels of PEEP and tidal volume on the partitioned respiratory mechanic (lung and chest wall), stress (transpulmonary pressure) and strain (inflated volume above the functional residual capacity). METHODS: The end-expiratory lung volume was measured using a simplified closed circuit helium dilution method. During an inspiratory and expiratory pause, the airway and esophageal pressure were measured. Transpulmonary pressure was computed as the difference between airway and esophageal pressure. RESULTS: Ten intubated sedated paralyzed healthy children and ten children with ARDS underwent a PEEP trial (4 and 12 cmH2O) with a tidal volume of 8, 10 and 12 ml/kgIBW. The two groups were comparable for age and BMI (2.5 [1.0-5.5] vs 3.0 [1.7-7.2] years and 15.1 +/- 2.4 vs 15.3 +/- 3.0 kg/m(2)). The functional residual capacity in ARDS patients was significantly lower as compared to the control group (10.4 [9.1-14.3] vs 16.6 [11.7-24.6] ml/kg, p = 0.04). The ARDS patients had a significantly lower respiratory system and lung compliance as compared to control subjects (9.9 +/- 5.0 vs 17.8 +/- 6.5, 9.3 +/- 4.9 vs 16.9 +/- 4.1 at 4 cmH2O of PEEP and 11.7 +/- 5.8 vs 23.7 +/- 6.8, 10.0 +/- 4.9 vs 23.4 +/- 7.5 at 12 cmH2O of PEEP). The compliance of the chest wall was similar in both groups (76.7 +/- 30.2 vs 94.4 +/- 76.4 and 92.6 +/- 65.3 vs 90.0 +/- 61.7 at 4 and 12 cmH2O of PEEP). The lung stress and strain were significantly higher in ARDS patients as compared to control subjects and were poorly related to airway pressure and tidal volume normalized for body weight. CONCLUSIONS: Airway pressures and tidal volume normalized to body weight are poor surrogates for lung stress and strain in mild pediatric ARDS. TRIAL REGISTRATION: Clinialtrials.gov NCT02036801. Registered 13 January 2014. PMID- 26847433 TI - Environmental endocrine disruptors: Effects on the human male reproductive system. AB - Incidences of altered development and neoplasia of male reproductive organs have increased during the last 50 years, as shown by epidemiological data. These data are associated with the increased presence of environmental chemicals, specifically "endocrine disruptors," that interfere with normal hormonal action. Much research has gone into testing the effects of specific endocrine disrupting chemicals (EDCs) on the development of male reproductive organs and endocrine related cancers in both in vitro and in vivo models. Efforts have been made to bridge the accruing laboratory findings with the epidemiological data to draw conclusions regarding the relationship between EDCs, altered development and carcinogenesis. The ability of EDCs to predispose target fetal and adult tissues to neoplastic transformation is best explained under the framework of the tissue organization field theory of carcinogenesis (TOFT), which posits that carcinogenesis is development gone awry. Here, we focus on the available evidence, from both empirical and epidemiological studies, regarding the effects of EDCs on male reproductive development and carcinogenesis of endocrine target tissues. We also critique current research methodology utilized in the investigation of EDCs effects and outline what could possibly be done to address these obstacles moving forward. PMID- 26847438 TI - Marked seasonality of Cyclospora cayetanensis infections: ten-year observation of hospital cases, Honduras. AB - BACKGROUND: Document seasonality occurrence and epidemiologic characteristics of Cyclospora cayetanensis infections during a 10-year period from patients consulting at the University Hospital, Honduras. METHODS: Retrospective non interventional hospital-based study analyzed laboratory results from the period 2002 to 2011 of fresh and Ziehl-Nielsen carbolfuchsin stained routine stool samples received for parasitologic examination. Sporadically a sample with numerous oocysts was allowed to sporulate in 2.5 % potassium dichromate confirming the presence of bi-cystic bi-zoic oocysts. RESULTS: A total of 35,157 fecal samples were examined during a ten-year span, of which a third (28.4 %) was stained by the Ziehl-Neelsen carbolfuchsin method diagnosing a total of 125 (1.3 %) C.cayetanensis infections. A statistically significant apparent seasonality was observed most years during May to August (range p < 0.036-0.001), with 83.3 % of 125 cases occurring in those rainy months. All C. cayetanensis cases came from urban poor neighborhoods; male/female relation was 1:1 except in 2006, when all patients were females (p = 0.05; r(2) = 22,448). Forty four point eight percent of the stool samples were diarrheic or liquid and 65.6 % infections were identified in children 10 years old or less. Enteric helminths and protozoa co infected Cyclospora positive patients in 52 instances.: 8 % Ascaris lumbricoides, 8 % Giardia duodenalis, 23.2 % Blastocystis spp. and less frequently Entamoeba histolytica/E. dispar, Strongyloides stercoralis, and Trichuris trichiura. CONCLUSIONS: Results suggest a seasonal pattern for Cyclospora infections diagnosed in a clinical setting during the rainy months in Tegucigalpa and surrounding areas. Community studies should be conducted to support or dispute these observations. PMID- 26847437 TI - Limited role of culture conversion for decision-making in individual patient care and for advancing novel regimens to confirmatory clinical trials. AB - BACKGROUND: Despite recent increased clinical trials activity, no regimen has proved able to replace the standard 6-month regimen for drug-sensitive tuberculosis. Understanding the relationship between microbiological markers measured during treatment and long-term clinical outcomes is critical to evaluate their usefulness for decision-making for both individual patient care and for advancing novel regimens into time-consuming and expensive pivotal phase III trials. METHODS: Using data from the randomized controlled phase III trial REMoxTB, we evaluated sputum-based markers of speed of clearance of bacilli: time to smear negative status; time to culture negative status on LJ or in MGIT; daily rate of change of log10(TTP) to day 56; and smear or culture results at weeks 6, 8 or 12; as individual- and trial-level surrogate endpoints for long-term clinical outcome. RESULTS: Time to culture negative status on LJ or in MGIT, time to smear negative status and daily rate of change in log10(TTP) were each independent predictors of clinical outcome, adjusted for treatment (p <0.001). However, discrimination between low and high risk patients, as measured by the c statistic, was modest and not much higher than the reference model adjusted for BMI, history of smoking, HIV status, cavitation, gender and MGIT TTP. CONCLUSIONS: Culture conversion during treatment for tuberculosis, however measured, has only a limited role in decision-making for advancing regimens into phase III trials or in predicting the outcome of treatment for individual patients. REMoxTB ClinicalTrials.gov number: NCT00864383. PMID- 26847439 TI - [Gender differences of psychological, nutritional, and physical fitness variables influencing obesity/overweight in Austrian children and adolescents]. AB - Eating behavior and physical activity behavior are under the control of certain cognitive patterns. 6600 adults and 4400 children/adolescents (8-18 years) were tested with the Obesity Diagnostics and Evaluation System (AD-EVA). Potentially significant gender differences will be detailed for the entire juvenile cohort, the subgroup of obese children/adolescents as compared to the adult cohort in this article.Among all the subscales tested, obese girls primarily showed significantly higher values of (preclinical) eating disorders than boys. These data are relevant for both prevention and health promotion.No significant differences were found in regard to sports motivation. This warrants facilitation of physical activity for both genders. Further, a male predilection for "Snacks" and "High-fat food" that could be found in the total representative study group, could not be verified in the subgroup of obese girls and boys, thus suggesting a similarily unhealthy eating behavior in both genders of juvenility. PMID- 26847440 TI - Polypharmacy, potentially inappropriate medication and cognitive status in Austrian nursing home residents: results from the OSiA study. AB - There is little research investigating polypharmacy and potentially inappropriate medications (PIM) in connection with cognitive status in residents of Austrian nursing homes. Our findings result from a cross-sectional survey of 425 residents (315 women, 110 men, mean 83.6 years) from 12 Austrian nursing homes. The number of systemically administered permanent prescription drugs was 8.99 +/- 3.9 and decreased significantly with increasing cognitive impairment. Irrespective of cognitive status, polypharmacy (> 5 individual substances) was present in approximately 75% of the residents. Hyper-polypharmacy (> 10 individual substances) was present among almost 50% of the cognitively intact residents, and hence, significantly more frequent as compared with the group with the lowest cognitive performance (23.4%). At least one PIM was found in 72.4% of residents regardless of cognitive status. Predominantly, PIMs consisted of tranquilizers, antipsychotics, osmotic laxatives, non-steroidal anti-inflammatory drugs (NSAIDs) and anticholinergics, where only the number of NSAIDs decreased significantly with increasing cognitive impairment. In summary, our study shows a continued high prevalence of polypharmacy and PIM in long-term care institutions in Austria. PMID- 26847441 TI - [Position paper on medication-related osteonecrosis of the jaw (MRONJ)]. AB - It is now 12 years since the first article on medication-related osteonecrosis of the jaw (MRONJ) was reported in 2003. The recognition of MRONJ is still inconsistent between physicians and dentists but it is without doubt a severe disease with impairment of oral health-related quality of life. This position paper was developed by three Austrian societies for dentists, oral surgeons and osteologists involved in this topic. This update contains amendments on the incidence, pathophysiology, diagnosis, staging and treatment and provides recommendations for management based on a multidisciplinary international consensus. The MRONJ can be a medication-related side effect of treatment of malignant and benign bone diseases with bisphosphonates (Bp), bevacizumab and denosumab (Dmab) as antiresorptive therapy. The incidence of MRONJ is highest in the oncology patient population (range 1-15 %), where high doses of these medications are used at frequent intervals. In the osteoporosis patient population, the incidence of MRONJ is estimated to be 0.001-0.01 %, marginally higher than the incidence in the general population (< 0.001 %). Other risk factors for MRONJ include glucocorticoid use, maxillary or mandibular bone surgery, poor oral hygiene, chronic inflammation, diabetes mellitus, ill-fitting dentures as well as other drugs, including antiangiogenic agents. Prevention strategies for MRONJ include elimination or stabilization of oral disease prior to initiation of antiresorptive agents, as well as maintenance of good oral hygiene. In those patients at high risk for the development of MRONJ, including cancer patients receiving high-dose BP or Dmab therapy, consideration should be given to withholding antiresorptive therapy following extensive oral surgery until the surgical site heals with mature mucosal coverage. Management of MRONJ is based on the stage of the disease, extent of the lesions and the presence of contributing drug therapy and comorbidity. Conservative therapy includes topical antibiotic oral rinses and systemic antibiotic therapy. Early data have suggested enhanced osseous wound healing with teriparatide in those patients without contraindications for its use. The MRONJ related to denosumab may resolve more quickly with a drug holiday than MRONJ related to bisphosphonates. Localized surgical debridement is indicated in advanced nonresponsive disease and has proven successful. More invasive surgical techniques are becoming increasingly more important. Prevention is the key for the management of MRONJ. This requires a close teamwork for the treating physician and the dentist. It is necessary that this information is disseminated to other relevant health care professionals and organizations. PMID- 26847442 TI - [Polypharmacy--activities of the social insurance in Austria]. AB - In Austria, about a quarter of the population older than 60 years receives more than five medicines per quarter at the expense of the statutory health insurance. Especially for older and multimorbid people the risk of adverse drug reactions increases by taking multiple drugs. The social insurance has initiated activities to direct the focus on the issue of polypharmacy and the associated problems. An information campaign with the title "Vorsicht Wechselwirkung" has been developed which addresses physicians and patients. Tailored to the target groups, useful information and assistance should contribute to strengthening the awareness and compliance, and to improving the quality of drug therapies. To specifically sensitize general practitioners to the issue of polypharmacy, the "Poly-rate" is calculated. It is used as a parameter to assess the extent of polypharmacy in a physician's practice, and is being sent to general practitioners by the social insurance for information purposes. PMID- 26847443 TI - [Baseline- and health enhancing physical activity in adults with obesity]. AB - Physical inactivity is one of the major risk factors for people to become overweight or obese. To achieve a substantial health benefit, adults should do at least 150 min of moderate or 75 min of high intensity aerobic activity per week and additionally they should do muscle strengthening exercises. This recommendation represents the lower limit and not the optimum. To loose body weight a significantly higher level of physical activity is required. Exercise programs can play an important part to reach the required level of health enhancing physical activity. The Austrian pilot projects "Aktiv Bewegt" and "GEHE Adipositas" showed that obese adults were interested in structured exercise programs and that they were also willing to use them. Clear defined quality criteria, the differentiation from conventional programs for already active and fit people and a recommendation from a doctor or other health professionals were important motivation reasons. PMID- 26847444 TI - [Not Available]. AB - Obesity is increasing worldwide in both sexes and a challenge for health professionals and the health care system. Women have more subcutaneous fat and are more insulin sensitive while men have more visceral and liver fat and higher cardiovascular risk. Women more often show the metabolically healthy obese phenotype than males. However, with increasing BMI the risk for type 2 diabetes and cardiovascular diseases increases more dramatically in women compared to males. Obese women suffer more from weight-related problems, have a higher rate of depression and seek more often medical help to reduce weight. Both biological factors and psychosocial factors contribute to the disease and interact with each other. In this special edition of the journal sex and gender aspects in prevention, treatment and development of complications will be discussed, as proposed by the Austrian Obesity Association. Data available from the Austrian population will be included in the Austrian Gender Obesity Report. PMID- 26847445 TI - Psychosocial impact of mast cell disorders: Pilot investigation of a rare and understudied disease. AB - Mast cell disorders are rare, chronic diseases involving unpredictable physical symptoms ranging in severity, duration, and frequency. Almost two-thirds of participants with these disorders ( n = 180) experienced clinically meaningful depressive symptoms. Depressed mood was associated with somatic symptomatology, poorer quality of life, lower resilience, and indirectly with ways of coping. Newly developed measures for this population performed psychometrically well. There was no gender difference in depression but women reported greater use of several ways of coping, greater disease-related distress, poorer quality of life, and more symptoms. Results underscore the need for further research and development of effective psychosocial interventions for this population. PMID- 26847446 TI - Study protocol for the Maule Cohort (MAUCO) of chronic diseases, Chile 2014-2024. AB - BACKGROUND: Maule Cohort (MAUCO), a Chilean cohort study, seeks to analyze the natural history of chronic diseases in the agricultural county of Molina (40,000 inhabitants) in the Maule Region, Chile. Molina's population is of particular interest because in the last few decades it changed from being undernourished to suffering excess caloric intake, and it currently has the highest national rates of cardiovascular diseases, stomach cancer and gallbladder cancer. Between 2009 and 2011 Molina's poverty rate dropped from 24.1 % to 13.5 % (national average 20.4 %); in this period the county went from insufficient to almost complete basic sanitation. Despite these advances, chemical pollutants in the food and air are increasing. Thus, in Molina risk factors typical of both under-developed and developed countries coexist, generating a unique profile associated with inflammation, oxidative stress and chronic diseases. METHODS/DESIGN: MAUCO is the core project of the recently established Advanced Center for Chronic Diseases (ACCDiS), Universidad de Chile & Pontificia Universidad Catolica de Chile. In this study, we are enrolling and following 10,000 adults aged 38 to 74 years over 10 years. All eligible Molina residents will be enrolled. Participants were identified through a household census. Consenting individuals answer an epidemiological survey exploring risk factors (psycho-social, pesticides, diet, alcohol, and physical activity), medical history and physical and cognitive conditions; provide fasting blood, urine, and saliva samples; receive an electrocardiogram, abdominal ultrasound and bio-impedance test; and take a hand grip strength test. These subjects will be re-interviewed after 2, 5 and 7 years. Active surveillance of health events is in place throughout the regional healthcare system. The MAUCO Bio-Bank will store 30 to 50 aliquots per subject using an NIH/NCI biorepository system for secure and anonymous linkage of samples with data. DISCUSSION: MAUCO's results will help design public health interventions tailored to agricultural populations in Latin America. PMID- 26847447 TI - The Association Between Receipt of Guideline-Concordant Long-Term Opioid Therapy and All-Cause Mortality. AB - PURPOSE: For patients receiving long-term opioid therapy (LtOT), the impact of guideline-concordant care on important clinical outcomes--notably mortality--is largely unknown, even among patients with a high comorbidity and mortality burden (e.g., HIV-infected patients). Our objective was to determine the association between receipt of guideline-concordant LtOT and 1-year all-cause mortality. METHODS: Among HIV-infected and uninfected patients initiating LtOT between 2000 and 2010 through the Department of Veterans Affairs, we used Cox regression with time-updated covariates and propensity-score matched analyses to examine the association between receipt of guideline-concordant care and 1-year all-cause mortality. RESULTS: Of 17,044 patients initiating LtOT between 2000 and 2010, 1048 patients (6%) died during 1 year of follow-up. Patients receiving psychotherapeutic co-interventions (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.51-0.75; P < 0.001) or physical rehabilitative therapies (HR 0.81; 95% CI 0.67-0.98; P = 0.03) had a decreased risk of all-cause mortality compared to patients not receiving these services, whereas patients prescribed benzodiazepines concurrent with opioids had a higher risk of mortality (HR 1.39; 95% CI 1.12-1.66; P < 0.001). Among patients with a current substance use disorder (SUD), those receiving SUD treatment had a lower risk of mortality than untreated patients (HR 0.47; 95% CI 0.32-0.68; P = < 0.001). No association was found between all-cause mortality and primary care visits (HR 1.12; 95% CI 0.90 1.26; P = 0.32) or urine drug testing (HR 0.96; 95% CI 0.78-1.17; P = 0.67). CONCLUSIONS: Providers should use caution in initiating LtOT in conjunction with benzodiazepines and untreated SUDs. Patients receiving LtOT may benefit from multi-modal treatment that addresses chronic pain and its associated comorbidities across multiple disciplines. PMID- 26847448 TI - Cardiopulmonary fitness, adiponectin, chemerin associated fasting insulin level in colorectal cancer patients. AB - PURPOSE: Since circulating level of insulin is associated with colorectal cancer prognosis, it is important to identify factors contributing to fasting insulin level in colorectal cancer patients. The purpose of the current study is to investigate the association of physical fitness, adiponectin, and chemerin levels with circulating level of insulin in colorectal cancer patients. METHODS: A total of 123 stage II-III colorectal cancer patients who completed standard cancer treatment were recruited. Anthropometric characteristics, fitness measurements, fasting insulin level, homeostasis model assessment of insulin resistance, lipid profiles, and adiponectin and chemerin levels were analyzed. RESULT: Cardiopulmonary fitness level inversely associated with fasting insulin levels (the least fit (1st tertile): 8.11 +/- 0.64, moderately fit (2nd tertile): 6.02 +/- 0.63, and highly fit (3rd tertile): 5.58 +/- 0.66 MUU/ml, unfit vs. moderately fit, p < 0.01; unfit vs. highly fit, p < 0.05) after adjustment for gender, age, stage, and BMI. In addition, fasting adiponectin and chemerin levels were associated with fasting insulin levels after adjustment for gender, age, stage, and BMI. In our combined analyses, participants with high adiponectin and low chemerin levels showed significantly lower fasting insulin levels (4.92 +/- 0.75 vs. 8.07 +/- 0.80 MUU/ml, p < 0.01) compared with participants with low adiponectin and high chemerin levels. Multiple linear regression analysis confirmed that cardiopulmonary fitness and adiponectin levels (beta = -0.299, p = 0.002; beta = -0.201, p = 0.033) were independently associated with fasting insulin level. CONCLUSION: Our results suggest that physical fitness and adiponectin and chemerin levels may contribute to circulating levels of insulin. These results suggest that exercise may influence the prognosis of colorectal cancer patients by influencing physical fitness level, circulating levels of adiponectin and chemerin. PMID- 26847449 TI - A psychosocial oncology program: perceptions of the telephone-triage assessment. AB - PURPOSE: Cancer can be a significant source of distress for patients and family members, which led to the creation of psychosocial oncology (PSO) programs across Canada. To access the PSO program at this institution, individuals are first triaged over the telephone by a clinical nurse specialist (CNS) who also provides psychosocial support during the call. In our study, we explored the perceptions of cancer patients or family members about their psychosocial telephone-triage assessment conducted by a CNS for a PSO program. METHODS: A qualitative descriptive design was used to explore the perceptions of nine cancer patients and family members triaged by the CNS for the PSO program. Audiotaped in-person interviews were transcribed verbatim and analyzed for themes and categories using a constant comparative method. RESULTS: Three major themes emerged: (1) Triage as a bridge to care, referred to the structure of telephone-triage and link to psychosocial services; (2) feeling a supportive presence, referred to the CNS' actions to foster a therapeutic relationship; and (3) different paths to tailored care, referred to the individualized strategies targeted to the participant's unique needs. As most participants described trusting the CNS, these three themes were found to emerge through a lens of trust. CONCLUSION: Overall, the telephone triage was able to address the concerns of many participants and provide individualized coping strategies and support. This study further demonstrates that psychosocial support can be provided during triage over the telephone. PMID- 26847450 TI - Stress ulcer prophylaxis in adult neurocritical care patients--no firm evidence for benefit or harm. PMID- 26847451 TI - Comparison of the directionality of the halogen, hydrogen, and lithium bonds between HOOOH and XF (X = Cl, Br, H, Li). AB - Detailed electrostatic potential (ESP) analyses were performed to compare the directionality of halogen bonds with those of hydrogen bonds and lithium bonds. To do this, the interactions of HOOOH with the molecules XF (X = Cl, Br, H, Li) were investigated. For each molecule, the percentage of the van der Waals (vdW) molecular surface that intersected with the ESP surface was used to roughly quantify the directionality of the halogen/hydrogen/lithium bond associated with the molecule. The size of the region of intersection was found to increase in the following order: ClF < BrF < HF < LiF. The maximum ESP in the region of intersection, V S, max, was observed to become more positive according to the sequence ClF < BrF < HF < LiF. For ClF and BrF, the positive electrostatic potential was concentrated in a very small region of the vdW molecular surface. On the other hand, for HF and LiF, the positive electrostatic potential was more diffusely scattered across the vdW surface than for ClF and BrF. Also, the optimized geometries of the dipolymers HOOOH... XF (X = Cl, Br, H, Li) indicated that halogen bonds are more directional than hydrogen bonds and lithium bonds, consistent with the results of ESP analyses. PMID- 26847452 TI - Ceramic Heads Decrease Metal Release Caused by Head-taper Fretting and Corrosion. AB - BACKGROUND: Metal release resulting from taper fretting and corrosion is a clinical concern, because wear and corrosion products may stimulate adverse local tissue reactions. Unimodular hip arthroplasties have a conical taper between the femoral head (head bore taper) and the femoral stem (stem cone taper). The use of ceramic heads has been suggested as a way of reducing the generation of wear and corrosion products from the head bore/stem cone taper junction. A previous semiquantitative study found that ceramic heads had less visual evidence of fretting-corrosion damage compared with CoCr heads; but, to our knowledge, no studies have quantified the volumetric material loss from the head bore and stem cone tapers of a matched cohort of ceramic and metal heads. QUESTIONS/PURPOSES: We asked: (1) Do ceramic heads result in less volume of material loss at the head stem junction compared with CoCr heads; (2) do stem cone tapers have less volumetric material loss compared with CoCr head bore tapers; (3) do visual fretting-corrosion scores correlate with volumetric material loss; and (4) are device, patient, or intraoperative factors associated with volumetric material loss? METHODS: A quantitative method was developed to estimate volumetric material loss from the head and stem taper in previously matched cohorts of 50 ceramic and 50 CoCr head-stem pairs retrieved during revision surgery for causes not related to adverse reactions to metal particles. The cohorts were matched according to (1) implantation time, (2) stem flexural rigidity, and (3) lateral offset. Fretting corrosion was assessed visually using a previously published four-point, semiquantitative scoring system. The volumetric loss was measured using a precision roundness machine. Using 24 equally spaced axial traces, the volumetric loss was estimated using a linear least squares fit to interpolate the as-manufactured surfaces. The results of this analysis were considered in the context of device (taper angle clearance, head size, head offset, lateral offset, stem material, and stem surface finish) and patient factors that were obtained from the patients' operative records (implantation time, age at insertion, activity level, and BMI). RESULTS: The cumulative volumetric material losses estimated for the ceramic cohort had a median of 0.0 mm(3) per year (range, 0.0 0.4 mm(3)). The cumulative volumetric material losses estimated for the CoCr cohort had a median of 0.1 mm(3) per year (range, 0.0-8.8 mm(3)). An order of magnitude reduction in volumetric material loss was found when a ceramic head was used instead of a CoCr head (p < 0.0001). In the CoCr cohort, the femoral head bore tapers had a median material loss of 0.02 mm(3) (range, 0.0-8.7 mm(3)) and the stem cone tapers had a median material loss of 0.0 mm(3) (range, 0.0-0.32 mm(3)/year). There was greater material loss from femoral head bore tapers compared with stem cone tapers in the CoCr cohort (p < 0.001). There was a positive correlation between visual scoring and volumetric material loss (Spearman's rho = 0.67, p < 0.01). Although visual scoring was effective for preliminary screening to separate tapers with no or mild damage from tapers with moderate to severe damage, it was not capable of discriminating in the large range of material loss observed at the taper surfaces with moderate to severe fretting-corrosion damage, indicated with a score of 3 or 4. We observed no correlations between volumetric material loss and device and patient factors. CONCLUSIONS: The majority of estimated material loss from the head bore-stem cone junctions resulting from taper fretting and corrosion was from the CoCr head bore tapers as opposed to the stem cone tapers. Additionally, the total material loss from the ceramic cohort showed a reduction in the amount of metal released by an order of magnitude compared with the CoCr cohort. CLINICAL RELEVANCE: We found that ceramic femoral heads may be an effective means by which to reduce metal release caused by taper fretting and corrosion at the head bore-stem cone modular interface in THAs. PMID- 26847453 TI - Antibacterial and Biocompatible Titanium-Copper Oxide Coating May Be a Potential Strategy to Reduce Periprosthetic Infection: An In Vitro Study. AB - BACKGROUND: Periprosthetic infections are devastating for patients and more efficacious preventive strategies are needed. Surface-modified implants using antibacterial coatings represent an option to cope with this problem; however, manufacturing limitations and cytotoxicity have curbed clinical translation. Among metals with antibacterial properties, copper has shown superior in vitro antibacterial performance while maintaining an acceptable cytotoxicity profile. A thin film containing copper could prevent early biofilm formation to limit periprosthetic infections. This pilot study presents the in vitro antibacterial effect, cytotoxicity, and copper ion elution pattern of a thin film of titanium copper oxide (TiCuO). QUESTIONS/PURPOSES: (1) Do titanium alloy (Ti6Al4V) discs coated with a thin film of TiCuO reduce Staphylococcus epidermidis biofilm and planktonic cell density compared with uncoated discs? (2) Do Ti6Al4V discs coated with a thin film of TiCuO affect normal human osteoblast viability compared with untreated cells? (3) Is copper ion concentration generated by coated discs lower than previously published copper ion concentrations that cause 50% toxicity in similar human cell lines in vitro (TC50)? METHODS: Ninety Ti6Al4V discs (12.5 mm diameter; 1.25 mm thick) were used in this study. Seventy-two Ti6Al4V discs were coated with a thin film of either titanium oxide (TiO) or TiCuO containing 20%, 40%, or 80% copper using high-power impulse magnetron sputtering (HiPIMS). Eighteen Ti6Al4V discs remained uncoated for control purposes. We tested antibacterial properties of S epidermidis grown on discs in wells containing growth medium. After 24 hours, planktonic bacteria as well as biofilms removed by sonication were quantitatively cultured. Annexin/Pi staining was used to quantify in vitro normal human osteoblast cell viability at 24 hours and Day 7, respectively. Copper elution was measured at Days 1, 2, 3, 7, 14, and 28 using an inductively coupled plasma mass spectrometer to analyze aliquots of culture medium. Copper ion concentration achieved at 24 hours was compared with previously published TC50 for gingival fibroblast, a phenotypically similar cell line with available data regarding copper ion exposure. RESULTS: Discs coated with TiCuO 80% copper showed greater biofilm and planktonic cell density reduction when compared with other tested compositions (analysis of variance [ANOVA]; p < 0.001). Discs coated with TiCuO 80% copper showed mean biofilm and planktonic cell density of 4.0 log10 (SD = 0.4) and 5.7 log10 (SD = 0.2). Discs coated with TiCuO 80% showed a mean difference in biofilm and planktonic cell density of 2.5 log10 (95% confidence interval [CI], 1.9-3.1 log10; p < 0.001) and 1.2 (95% CI, 0.6-1.8; p < 0.001), respectively, when compared with uncoated discs. Normal human osteoblast viability did not differ among all groups at 24 hours (ANOVA; p = 0.2) and Day 7 (ANOVA; p = 0.7). Discs coated with TiCuO 80% copper showed a mean difference (95% CI) in relative cell viability (%) at 24 hours and Day 7 of 31.1 (95% CI, -19.4 to 81.7; p = 0.4) and -5.0 (95% CI, -7.8 to 17.9; p = 0.9), respectively, when compared with untreated cells. For all TiCuO-coated discs, copper ion elution peaked at 24 hours and slowly decreased in a curvilinear fashion to nearly undetectable levels by Day 28. Discs coated with TiCuO 80% copper showed mean copper ion concentration at 24 hours of 269.4 umol/L (SD = 25.2 umol/L) and this concentration was lower than previously published TC50 for similar human cell lines at 24 hours (344 umol/L, SEM = 44 umol/L). CONCLUSIONS: This pilot study demonstrates a proof of concept that a thin-film implant coating with TiCuO can provide a potent local antibacterial environment while remaining relatively nontoxic to a human osteoblast cell line. Further research in an animal model will be necessary to establish efficacy and safety of this technique and whether it might be useful in the design of implants. CLINICAL RELEVANCE: A thin film coating with TiCuO demonstrates high antibacterial activity and low cellular cytotoxicity to human osteoblasts in vitro. Taken together, these properties represent a potential strategy for preventing periprosthetic infection if further work in animal models can confirm these results in vivo. PMID- 26847454 TI - Can Vascular Injury be Appropriately Assessed With Physical Examination After Knee Dislocation? AB - BACKGROUND: Knee dislocations are rare injuries with potentially devastating vascular complications. An expeditious and accurate diagnosis is necessary, as failing to diagnose vascular injury can result in amputation; however, the best diagnostic approach remains controversial. QUESTIONS/PURPOSES: We asked: (1) What patient factors are predictors of vascular injury after knee dislocation? (2) What are the diagnostic utilities of palpable dorsalis pedis or posterior tibial pulses, and the presence of an ankle-brachial index (ABI) of 0.9 or greater? METHODS: A database at a Level I trauma center was queried for patients with evidence of knee dislocation, demographic information (age at the time of injury, sex, Injury Severity Score, BMI, mechanism of injury), and the presence of open injury were recorded. One-hundred forty-one patients underwent screening at initial presentation, of whom 26 (24%) underwent early vascular exploration based on an abnormal physical examination. One-hundred five (91%) of the remaining 115 patients were available at a minimum followup of 6 months (mean, 19 +/- 10 months). In total, 31 unique patients were excluded, including 10 patients (7%) who were lost to followup before 6 months. Among the 110 patients who met inclusion criteria, the mean age and SD was 37 +/- 13 years, and the Injury Severity Score was 15 +/- 9. There were 71 males (65%). Logistic regression was used to determine independent correlates of vascular injury. The vascular examination was reviewed for the presence of a palpable pulse in the dorsalis pedis artery, the presence of a palpable pulse in the posterior tibial artery, and whether the ABI in the dorsalis pedis was 0.9 or greater. Contingency tables were generated to assess the sensitivity, specificity, and accuracy of physical examination maneuvers. The physical examination was collectively regarded as "normal" when both pulses were palpable and the ABI was 0.9 or greater. The initial physical examination as just described was considered the diagnostic test being evaluated in this study; "positive" tests were evaluated by and confirmed at vascular surgery, and 6 months clinical followup without symptoms or progressive signs of vascular injury confirmed the absence of injury in the remainder of the patients. Contingency tables were generated again to assess the sensitivity, specificity, and accuracy of the combined physical examination. RESULTS: Increased BMI (odds ratio [OR], 1.077; 95% CI, 1.008-1.155; p = 0.033) and open injuries (OR, 3.366; 95% CI, 1.008-11.420; p = 0.048) were associated with vascular injury. No single physical examination maneuver had a 100% sensitivity for ruling out vascular injury. A normal physical examination (palpable pulses and ABI >= 0.9) had 100% sensitivity for ruling out vascular injury. CONCLUSIONS: Increased BMI and the presence of open dislocation are associated with a greater risk for vascular injury after knee dislocation. The combination of a palpable dorsalis pedis and posterior tibial pulse combined with an ABI of 0.9 or greater was 100% sensitive for the detection of vascular injury based on clinical followup at 6 months. LEVEL OF EVIDENCE: Level III, diagnostic study. PMID- 26847455 TI - To Cast, to Saw, and Not to Injure: Can Safety Strips Decrease Cast Saw Injuries? AB - BACKGROUND: Placement and removal of fiberglass casts are among the more-common interventions performed in pediatric orthopaedic surgery offices. However, cast removal is associated with abrasive injuries and burns from the oscillating cast saw, and these injuries can occur even when the cast is removed by experienced personnel. It is unknown whether an added barrier, such as a safety strip, can mitigate injuries from blade-to-skin contact during cast removal with the oscillating saw. QUESTIONS/PURPOSES: We asked: (1) Can a safety strip provide a physical barrier during cast removal, decreasing blade-to-skin contact? (2) Does the safety strip lessen heat transfer? (3) Will the use of the safety strip prevent cast pressure from being released when the cast is split? METHODS: Standard long-arm fiberglass casts were removed by experienced and inexperienced healthcare personnel (n = 35) from life-sized pediatric models. A commercially available woven cast saw safety strip, commonly incorporated in waterproof cast constructs, was chosen as the protective strip. Each participant removed a cast with and without the safety strip present. All participants were blinded to the presence or absence of the safety strip at the time of cast removal. The number of touches was compared between cast removal with and without protective strips. A separate model was designed to assess prevention of heat transfer. Temperatures were recorded, using thermocouples, for three designated temperatures. Five to six trials were conducted at each designated temperature for each of two conditions, with and without the safety strip. Finally, to assess if the safety strip would prevent cast pressure from being released, a third model was used. Thirty standard short-arm casts were applied and removed from the arm models by one of the authors. Pressure data were collected from between the padding layers, in casts with and without the safety strip present, after application, univalving and bivalving each cast. RESULTS: Use of the safety strip reduced the number of simulated skin touches compared with casts removed without the safety strip, among experienced users (mean, 9.0 [range, 1-28] versus 0.1 [range, 0-1], mean ratio, 0.0012; 95% CI, 0.002-0.063; p < 0.001) and inexperienced users (mean, 8.5 [range, 0-31] versus 0.6 [range, 0-3], mean ratio, 0.07; 95% CI, 0.03-0.15; p < 0.001). The safety strips decreased heat transfer, preventing temperatures at the cast-skin interface from reaching 50 degrees C. Finally, after splitting the cast, with the numbers available, there was no increase in the pressure beneath the casts in those with the safety strip present (mean without, 0.23 [SD, 0.070] versus safety strip in the padding 0.20 [SD, 0.091] and safety strip on top padding, 0.21 [SD, 0.090]; p = 0.446 and p = 0.65 respectively). CONCLUSIONS: Our study showed the effectiveness of a safety strip in reducing simulated touches with the oscillating cast saw during cast splitting. Additional studies are warranted to investigate the clinical use and utility of the safety strip in practice. CLINICAL RELEVANCE: The findings of this study suggest that using safety strips in clinical practice could decrease blade-to-skin contact and therefore minimize cast saw injuries. However, validation of these findings in the clinical setting is necessary before drawing a definitive conclusion. PMID- 26847456 TI - Strategies of offspring investment and dispersal in a spatially structured environment: a theoretical study using ants. AB - BACKGROUND: Offspring investment strategies vary markedly between and within taxa, and much of this variation is thought to stem from the trade-off between offspring size and number. While producing larger offspring can increase their competitive ability, this often comes at a cost to their colonization ability. This competition-colonization trade-off (CCTO) is thought to be an important mechanism supporting coexistence of alternative strategies in a wide range of taxa. However, the relative importance of an alternative and possibly synergistic mechanism-spatial structuring of the environment-remains the topic of some debate. In this study, we explore the influence of these mechanisms on metacommunity structure using an agent-based model built around variable life history traits. Our model combines explicit resource competition and spatial dynamics, allowing us to tease-apart the influence of, and explore the interaction between, the CCTO and the spatial structure of the environment. We test our model using two reproductive strategies which represent extremes of the CCTO and are common in ants. RESULTS: Our simulations show that colonisers outperform competitors in environments subject to higher temporal and spatial heterogeneity and are favoured when agents mature late and invest heavily in reproduction, whereas competitors dominate in low-disturbance, high resource environments and when maintenance costs are low. Varying life-history parameters has a marked influence on coexistence conditions and yields evolutionary stable strategies for both modes of reproduction. Nonetheless, we show that these strategies can coexist over a wide range of life-history and environmental parameter values, and that coexistence can in most cases be explained by a CCTO. By explicitly considering space, we are also able to demonstrate the importance of the interaction between dispersal and landscape structure. CONCLUSIONS: The CCTO permits species employing different reproductive strategies to coexist over a wide range of life-history and environmental parameters, and is likely to be an important factor in structuring ant communities. Our consideration of space highlights the importance of dispersal, which can limit the success of low dispersers through kin competition, and enhance coexistence conditions for different strategies in spatially structured environments. PMID- 26847457 TI - Transforming growth factor-beta 1 produced by vascular smooth muscle cells predicts fibrosis in the gastrocnemius of patients with peripheral artery disease. AB - BACKGROUND: Lower leg ischemia, myopathy, and limb dysfunction are distinguishing features of peripheral artery disease (PAD). The myopathy of PAD is characterized by myofiber degeneration in association with extracellular matrix expansion, and increased expression of transforming growth factor-beta 1 (TGF-beta1; a pro fibrotic cytokine). In this study, we evaluated cellular expression of TGF-beta1 in gastrocnemius of control (CTRL) and PAD patients and its relationship to deposited collagen, fibroblast accumulation and limb hemodynamics. METHODS: Gastrocnemius biopsies were collected from PAD patients with claudication (PAD II; N = 25) and tissue loss (PAD-IV; N = 20) and from CTRL patients (N = 20). TGF beta1 in slide-mounted specimens was labeled with fluorescent antibodies and analyzed by quantitative wide-field, fluorescence microscopy. We evaluated co localization of TGF-beta1 with vascular smooth muscle cells (SMC) (high molecular weight caldesmon), fibroblasts (TE-7 antigen), macrophages (CD163), T cells (CD3) and endothelial cells (CD31). Collagen was stained with Masson Trichrome and collagen density was determined by quantitative bright-field microscopy with multi-spectral imaging. RESULTS: Collagen density increased from CTRL to PAD-II to PAD-IV specimens (all differences p < 0.05) and was prominent around microvessels. TGF-beta1 expression increased with advancing disease (all differences p < 0.05), correlated with collagen density across all specimens (r = 0.864; p < 0.001), associated with fibroblast accumulation, and was observed exclusively in SMC. TGF-beta1 expression inversely correlated with ankle-brachial index across PAD patients (r = -0.698; p < 0.001). CONCLUSIONS: Our findings support a progressive fibrosis in the gastrocnemius of PAD patients that is caused by elevated TGF-beta1 production in the SMC of microvessels in response to tissue hypoxia. PMID- 26847459 TI - Ethnobotanical perspective of antimalarial plants: traditional knowledge based study. AB - BACKGROUND: Considering the demand of antimalarial plants it has become essential to find and locate them for their optimal extraction. The work aims to find plants with antimalarial activities which were used by the local people; to raise the value of traditional knowledge system (TKS) prevalent in the study region; to compile characteristics of local plants used in malaria treatment (referred as antimalarial plants) and to have its spatial distribution analysis to establish a concept of geographical health. METHODS: Antimalarial plants are listed based on literature survey and field data collected during rainy season, from 85 respondents comprised of different ethnic groups. Ethno-medicinal utilities of plants was extracted; botanical name, family, local name, part used, folklore, geographical location and image of plants were recorded after cross validating with existing literatures. The interview was trifurcated in field, Vaidya/Hakims and house to house. Graphical analysis was done for major plants families, plant part used, response of people and patients and folklore. Mathematical analysis was done for interviewee's response, methods of plant identification and people's preferences of TKS through three plant indices. RESULTS: Fifty-one plants belonging to 27 families were reported with its geographical attributes. It is found plant root (31.75 %) is used mostly for malaria treatment and administration mode is decoction (41.2 %) mainly. The study area has dominance of plants of family Fabaceae (7), Asteraceae (4), Acanthaceae (4) and Amaranthaceae (4). Most popular plants found are Adhatoda vasica, Cassia fistula and Swertia chirata while % usage of TKS is 82.0 % for malaria cure. CONCLUSION: The research findings can be used by both scientific community and common rural people for bio-discovery of these natural resources sustainably. The former can extract the tables to obtain a suitable plant towards finding a suitable lead molecule in a drug discovery project; while the latter can meet their local demands of malaria, scientifically. PMID- 26847458 TI - Emerging evidence for beneficial macrophage functions in atherosclerosis and obesity-induced insulin resistance. AB - The discovery that obesity promotes macrophage accumulation in visceral fat led to the emergence of a new field of inquiry termed "immunometabolism". This broad field of study was founded on the premise that inflammation and the corresponding increase in macrophage number and activity was a pathologic feature of metabolic diseases. There is abundant data in both animal and human studies that supports this assertation. Established adverse effects of inflammation in visceral fat include decreased glucose and fatty acid uptake, inhibition of insulin signaling, and ectopic triglyceride accumulation. Likewise, in the atherosclerotic plaque, macrophage accumulation and activation results in plaque expansion and destabilization. Despite these facts, there is an accumulating body of evidence that macrophages also have beneficial functions in both atherosclerosis and visceral obesity. Potentially beneficial functions that are common to these different contexts include the regulation of efferocytosis, lipid buffering, and anti-inflammatory effects. Autophagy, the process by which cytoplasmic contents are delivered to the lysosome for degradation, is integral to many of these protective biologic functions. The macrophage utilizes autophagy as a molecular tool to maintain tissue integrity and homeostasis at baseline (e.g., bone growth) and in the face of ongoing metabolic insults (e.g., fasting, hypercholesterolemia, obesity). Herein, we highlight recent evidence demonstrating that abrogation of certain macrophage functions, in particular autophagy, exacerbates both atherosclerosis and obesity-induced insulin resistance. Insulin signaling through mammalian target of rapamycin (mTOR) is a crucial regulatory node that links nutrient availability to macrophage autophagic flux. A more precise understanding of the metabolic substrates and triggers for macrophage autophagy may allow therapeutic manipulation of this pathway. These observations underscore the complexity of the field "immunometabolism", validate its importance, and raise many fascinating and important questions for future study. PMID- 26847460 TI - In vitro synergistic effects of chlorpromazine and sertraline in combination with amphotericin B against Cryptococcus neoformans var. grubii. AB - Cryptococcus neoformans is encapsulated yeast that causes cryptococcosis. The cryptococcal meningitis may cause neuropsychiatric symptoms. Here, we evaluated the in vitro activity of amphotericin B (AMB), chlorpromazine (CLOR), and sertraline (SERT) alone or in combination against clinical isolates of C. neoformans considering the capsular induction in vitro. Susceptibility tests were carried out using the broth microdilution method in accordance with the CLSI document M27-A3. The combination [CLOR + AMB] exhibited synergism for 50 and 67 % of strains before capsular induction (group I) and after capsular induction (group II), respectively. The combination [SERT + AMB] showed 60 % of synergism against the both groups. Antagonism was not observed. Our results show the therapeutic potential of chlorpromazine and sertraline in combination with amphotericin B against neurocryptococcosis. PMID- 26847461 TI - A simple, fast and reproducible echocardiographic approach to grade left ventricular diastolic function. AB - The American Society of Echocardiography and European Association of Echocardiography (ASE/EAE) have published an algorithm for the grading of diastolic function. However, the ability to use this algorithm effectively in daily clinical practice has not been investigated. We hypothesized that in some patients it may be difficult to grade diastolic dysfunction with this scheme, since there may be discrepancies in the assessed parameters. The aim of the current study was to test the feasibility of the ASE/EAE algorithm and to compare this with a new Thoraxcenter (TXC) algorithm. The ASE/EAE and TXC algorithms were applied to 200 patients. The ASE/EAE algorithm starts with assessment of diastolic myocardial wall velocities and left atrial (LA) volumes with subsequent assessment of E/A ratio, E-wave deceleration time and pulmonary venous flow. The TXC algorithm reverses these steps, uses LA dimension instead of volume and does not include a Valsalva manoeuvre and pulmonary venous flow. Due to inconsistencies between diastolic myocardial wall velocities and LA volumes and a not covered E/A ratio in the range of 1.5-2 it was not possible to classify 48 % of patients with the ASE/EAE algorithm, as opposed to only 10 % by the TXC algorithm. LA volume was always needed in the ASE/EAE algorithm. In only 64 % of patients LA size was necessary by the TXC algorithm. When LA volume would have been used instead of LA dimension, grading of LV diastolic function would have been different in only 2 % of patients without apparent improvement. Assessment of LA dimension was considerably faster than LA volume. The TXC algorithm to grade LV diastolic dysfunction was compared to the ASE/EAE algorithm simpler, faster, better reproducible and yields a higher diagnostic outcome. PMID- 26847463 TI - National smoking bans improve health outcomes, Cochrane review shows. PMID- 26847464 TI - Impact of Knowledge, Self-Efficacy, and Perceived Importance on Steps Taken Toward Cancer Prevention Among College Men and Women. AB - The incidence of skin, most HPV-related, liver, and lung cancers can be reduced through primary prevention. Morbidity from breast and testicular cancers can be reduced through secondary prevention. Thus, it is important to understand the mechanisms that predict engagement in primary and secondary prevention behaviors for these cancers. We investigated the roles of knowledge of cancer prevention, perceived importance of cancer prevention, and self-efficacy to engage in prevention steps in order to predict college students' actual engagement in cancer prevention behaviors (CPB). Participants were 315 undergraduates who completed an online survey to assess these constructs. Hierarchical linear regression analyses were used to model knowledge, self-efficacy, and perceived importance as predictors of CPB for a range of cancers. Self-efficacy predicted CPB similarly across all cancers such that having a higher level of self-efficacy to prevent the cancer predicted having engaged in more CPB. Increase in knowledge predicted an increase in the frequency of CPB for skin and HPV-related cancers. Perceived importance of prevention predicted skin cancer CPB. These findings can be used to tailor cancer prevention programs for undergraduates to achieve greatest impact. PMID- 26847462 TI - An integrated in silico approach for functional and structural impact of non- synonymous SNPs in the MYH1 gene in Jeju Native Pigs. AB - BACKGROUND: This study was performed to identify the non- synonymous polymorphisms in the myosin heavy chain 1 gene (MYH1) association with skeletal muscle development in economically important Jeju Native Pig (JNP) and Berkshire breeds. Herein, we present an in silico analysis, with a focus on (a) in silico approaches to predict the functional effect of non-synonymous SNP (nsSNP) in MYH1 on growth, and (b) molecular docking and dynamic simulation of MYH1 to predict the effects of those nsSNP on protein-protein association. RESULTS: The NextGENe (V 2.3.4.) tool was used to identify the variants in MYH1 from JNP and Berkshire using RNA seq. Gene ontology analysis of MYH1 revealed significant association with muscle contraction and muscle organ development. The 95 % confidence intervals clearly indicate that the mRNA expression of MYH1 is significantly higher in the Berkshire longissimus dorsi muscle samples than JNP breed. Concordant in silico analysis of MYH1, the open-source software tools identified 4 potential nsSNP (L884T, K972C, N981G, and Q1285C) in JNP and 1 nsSNP (H973G) in Berkshire pigs. Moreover, protein-protein interactions were studied to investigate the effect of MYH1 mutations on association with hub proteins, and MYH1 was found to be closely associated with the protein myosin light chain, phosphorylatable, fast skeletal muscle MYLPF. The results of molecular docking studies on MYH1 (native and 4 mutants) and MYLFP demonstrated that the native complex showed higher electrostatic energy (-466.5 Kcal mol(-1)), van der Walls energy (-87.3 Kcal mol(-1)), and interaction energy (-835.7 Kcal mol(-1)) than the mutant complexes. Furthermore, the molecular dynamic simulation revealed that the native complex yielded a higher root-mean-square deviation (0.2-0.55 nm) and lower root-mean-square fluctuation (approximately 0.08-0.3 nm) as compared to the mutant complexes. CONCLUSIONS: The results suggest that the variants at L884T, K972C, N981G, and Q1285C in MYH1 in JNP might represent a cause for the poor growth performance for this breed. This study is a pioneering in-depth in silico analysis of polymorphic MYH1 and will serve as a valuable resource for further targeted molecular diagnosis and population-based studies conducted for improving the growth performance of JNP. PMID- 26847465 TI - Clinical Research Recession: Training Needs Perception Among Medical Students. AB - Clinical research is an integrated part of medical education. There is a noticeable decrease in the number of physician-scientists in developing countries, which is reflected by a decrease in research output and publications from these countries. We conducted a survey aiming to identify the gaps in clinical research training from the perspective of medical students. The results can be used to customize future clinical research trainings. The survey tool was divided into six modules which represent the cornerstones of clinical research based on similar surveys done for the same purpose. For each module, questions covered the perceived knowledge of its aspects and how much relevant the responder thought it was to clinical research. Five hundred one candidates have filled the survey. Evidence-based medicine (EBM) had the highest knowledge score of 2.20/4, while "clinical trials execution" knowledge got the lowest score of 1.64/4. Responders perceived EBM as the most relevant aspect of clinical research (3.39/4), while research ethics received the lowest score 3.18/4. "Clinical trials execution" had the largest gap of a difference calculated as 1.60, while EBM had the lowest gap of 1.20. More attention must be paid to clinical research training for medical students in developing countries. These trainings have to be customized to focus on clinical trial execution, research methodology, and biostatistics. In parallel, awareness campaigns targeted toward the medical community emphasizing the importance of the ethics as an aspect of clinical research should be established. PMID- 26847466 TI - Impact of a 3-Day Introductory Oncology Course on First-Year International Medical Students. AB - Although only some medical students will choose cancer as their specialty, it is essential that all students have a basic understanding of cancer and its treatment. The purpose of this study was to evaluate the impact of an introductory clinical oncology course on first-year international medical students. Evaluation of the course involved a quantitative survey designed for this study that was given pre- and post-course completion. Participants included 29 first-year international medical students. Students reported that the course affected them emotionally more than they anticipated it would prior to beginning the course. By the end of the course, students felt more comfortable focusing on how to live with cancer, felt less afraid of dealing with death, and were better able to cope with uncomfortable emotional situations. The course had no significant effect on students' interest in specializing in oncology in the future. Our study provides evidence that an introductory oncology course can increase student comfort with issues related to living with cancer, with confronting and dealing with death and dying, and with coping with uncomfortable emotional situations as related to cancer care. In anticipation of growing shortages in oncology specialists in the coming years, the ability of an early course in oncology to attract more students to the field is of interest. Future research should examine ethnic and cultural differences in uptake of the clinical oncology courses across continents and should use direct observation in addition to self-report in evaluating outcomes. PMID- 26847467 TI - Preparation of Bottlebrush Polymers via a One-Pot Ring-Opening Polymerization (ROP) and Ring-Opening Metathesis Polymerization (ROMP) Grafting-Through Strategy. AB - Bottlebrush polymers are synthesized using a tandem ring-opening polymerization (ROP) and ring-opening metathesis polymerization (ROMP) strategy. For the first time, ROP and ROMP are conducted sequentially in the same pot to yield well defined bottlebrush polymers with molecular weights in excess of 10(6) Da. The first step of this process involves the synthesis of a polylactide macromonomer (MM) via ROP of d,l-lactide initiated by an alcohol-functionalized norbornene. ROMP grafting-through is then carried out in the same pot to produce the bottlebrush polymer. The applicability of this methodology is evaluated for different MM molecular weights and bottlebrush backbone degrees of polymerization. Size-exclusion chromatographic and (1)H NMR spectroscopic analyses confirm excellent control over both polymerization steps. In addition, bottlebrush polymers are imaged using atomic force microscopy and stain-free transmission electron microscopy on graphene oxide. PMID- 26847468 TI - Too early and too northerly: evidence of temperate trees in northern Central Europe during the Younger Dryas. AB - This paper presents highly unexpected paleobotanical data. Eight (14) C accelerator mass spectrometry (AMS) dates of soil macrocharcoal pieces, identified taxonomically, indicate the presence of oak and beech in the Younger Dryas, and pine in the Allerod, in the northernmost low mountain range of Central Europe, the Harz Mountains, in Germany. If the presence of pine at such latitude and periods is not surprising, the presence of temperate-adapted trees is highly improbable, because they are assumed to have reached the area from a southern location several thousand years later. Two hypotheses are postulated to explain this record. Both are related to the warm periods of the Bolling and Allerod: the classically 'short' duration of this warm period makes the migration of the temperate trees from the identified refuge areas in the southern location implausible, and so the presence of intermediary microrefugia at a medium latitude in Central Europe is postulated; recent data reveal that the warm period of the Late Glacial phase was much longer than considered in the classical view and, thus, would be long enough for a northward migration of temperate-adapted trees. Although our dataset does not permit disentanglement of these hypotheses, it provides significant innovative insights for the biogeography of Central Europe. PMID- 26847469 TI - The memory effect of magnetoelectric coupling in FeGaB/NiTi/PMN-PT multiferroic heterostructure. AB - Magnetoelectric coupling effect has provided a power efficient approach in controlling the magnetic properties of ferromagnetic materials. However, one remaining issue of ferromagnetic/ferroelectric magnetoelectric bilayer composite is that the induced effective anisotropy disappears with the removal of the electric field. The introducing of the shape memory alloys may prevent such problem by taking the advantage of its shape memory effect. Additionally, the shape memory alloy can also "store" the magnetoelectric coupling before heat release, which introduces more functionality to the system. In this paper, we study a FeGaB/NiTi/PMN-PT multiferroic heterostructure, which can be operating in different states with electric field and temperature manipulation. Such phenomenon is promising for tunable multiferroic devices with multi functionalities. PMID- 26847470 TI - Urinary alpha1 -microglobulin and albumin excretion in children and adolescents with type 1 diabetes. AB - BACKGROUND: The present study investigated the correlation between urinary alpha1 -microglobulin as a marker of tubular dysfunction and albumin excretion in children and adolescents with type 1 diabetes (T1D). METHODS: Ninety-two Egyptian patients with T1D were included in the study (mean [+/- SD] age 14.14 +/- 5.13 years). The duration of diabetes in all patients was >5 years (mean [+/- SD] duration 8.28 +/- 2.62 years) and all had normal renal function. Forty healthy subjects were also included as a control group. Urinary albumin excretion was assessed in all patients and urinary alpha1 -microglobulin was measured in both patients and control in the morning urine specimen. RESULTS: Analysis of the results showed that patients had significantly higher levels of urinary alpha1 microglobulin than the controls (P < 0.01). Among the patients, there was a strong positive correlation between urinary alpha1 -microglobulin and urinary albumin excretion (P < 0.01). Positive correlations were also found between urinary alpha1 -microglobulin and duration of diabetes (P < 0.01), HbA1c (P < 0.05), and fasting and postprandial blood glucose (P < 0.05 for both). CONCLUSION: The present study shows that urinary alpha1 -microglobulin is strongly correlated with urinary albumin excretion in children and adolescents with T1D. In addition, it demonstrates the importance of tubular dysfunction as an early and integral component of diabetic nephropathy syndrome in these patients. The results of the present study emphasize the value of tight glycemic control in slowing the progression of tubular dysfunction, especially in patients with a longer duration of diabetes. PMID- 26847471 TI - Monte Carlo simulations of the static friction between two grafted polymer brushes. AB - A configurational bias Monte Carlo method has been developed to study the static friction between grafted polymers immersed in a good solvent. Simple models using the soft quadratic potential from a dissipative particle dynamics study have been used to model polyzwitterionic brushes at physiological pressures (up to 7.5 MPa). Three models of decreasing rigidity have been used to model the friction between the brushes by calculating the tangential component of the pressure induced by a mismatch in the registry of the two grafting surfaces. The static friction coefficient can be calculated for three model systems and the slip between the layers occurs at a much lower values of shear force for the more flexible polymer layer. A moderate increase in the flexibility of the chains reduces the friction coefficient by a factor of ca. 20. Tilting the layer directors of the brushes also increases the static friction between the layer when the top, tilted layer is displaced in the direction away from the tilt. Non equilibrium dynamics techniques for the same model were performed using dissipative particle dynamics and the limiting extremes of the Stribeck curve corresponding to the boundary lubrication regime and the hydrodynamic lubrication regime were observed for these flat surfaces. As expected, MUk is significantly lower than MUs for the same system. The dynamical friction coefficients in the model are in good agreement with those observed in the experiment and the ratio of MUk/MUs of between 0.11 and 0.5 observed in the simulations is in reasonable agreement with the value of 0.5 normally observed for these seen for these systems. PMID- 26847472 TI - A Solvent-Free Hot-Pressing Method for Preparing Metal-Organic-Framework Coatings. AB - Metal-organic frameworks (MOFs), with their well-defined pores and rich structural diversity and functionality, have drawn a great deal of attention from across the scientific community. However, industrial applications are hampered by their intrinsic fragility and poor processability. Stable and resilient MOF devices with tunable flexibility are highly desirable. Herein, we present a solvent- and binder-free approach for producing stable MOF coatings by a unique hot-pressing (HoP) method, in which temperature and pressure are applied simultaneously to facilitate the rapid growth of MOF nanocrystals onto desired substrates. This strategy was proven to be applicable to carboxylate-based, imidazolate-based, and mixed-metal MOFs. We further successfully obtained superhydrophobic and "Janus" MOF films through layer-by-layer pressing. This HoP method can be scaled up in the form of roll-to-roll production and may push MOFs into unexplored industrial applications. PMID- 26847474 TI - Carbon-atom wires: 1-D systems with tunable properties. AB - This review provides a discussion of the current state of research on linear carbon structures and related materials based on sp-hybridization of carbon atoms (polyynes and cumulenes). We show that such systems have widely tunable properties and thus represent an intriguing and mostly unexplored field for both fundamental and applied sciences. We discuss the rich interplay between the structural, vibrational, and electronic properties focusing on recent advances and the future perspectives of carbon-atom wires and novel hybrid sp-sp(2)-carbon architectures. PMID- 26847473 TI - Transoral robotic resection of a large schwannoma in the retropharyngeal space. AB - BACKGROUND: External approaches have been traditionally used for the complete excision of large retropharyngeal space lesions. CASE REPORT: This paper describes a case of a large schwannoma of the retropharyngeal space excised transorally with the use of a robotic system. This lesion measured 2.7 * 1.2 cm in axial dimensions and over 5.8 cm in craniocaudal length. The lesion was delivered en bloc with an intact capsule. No peri- or post-operative complications were encountered. The procedure allowed quick resumption of an oral diet and a return to normal activity for the patient. CONCLUSION: This is, to our knowledge, the first report of this technique used in the excision of a large retropharyngeal space mass. PMID- 26847475 TI - siRNA-induced TRAF6 knockdown promotes the apoptosis and inhibits the invasion of human lung cancer SPC-A1 cells. AB - Tumor necrosis factor receptor-associated factor 6 (TRAF6) has been found to be involved in multiple cancers. However, the effect of small interfering RNA (siRNA)-induced knockdown of TRAF6 on the biological behaviors of cancer cells remains unknown. Thus, the present study aimed to investigate the effect of siRNA induced knockdown of TRAF6 on the biological behaviors of human lung cancer SPC A1 cells. The expression of TRAF6 was determined in human lung adenocarcinoma A549, non-small cell lung cancer H1650, human airway epithelial Calu-3 and human lung cancer SPC-A1 cell lines using quantitative RT-PCR (qRT-PCR) and western blotting at the transcriptional and translational levels. TRAF6 expression was knocked down in the SPC-A1 cells using an siRNA technique, and the effects of TRAF6 knockdown on NF-kappaB activity, cell proliferation, apoptosis, cell cycle, invasion and migration of the SPC-A1 cells were determined using electrophoretic mobility shift assay (EMSA), cell proliferation assay, flow cytometry, Transwell invasion assay and scratch wound assay. In addition, the protein expression of CD24, CXCR4, MMP1, MMP2, MMP9, TWIST, TIMP-2 and Slug was quantified using western blotting assay. Western blotting and qRT-PCR assays showed upregulation of TRAF6 at both the translational and transcriptional levels in the Calu-3 and SPC-A1 cells, and K63-linked ubiquitination of TRAF6 and constitutive NF-kappaB activation were detected in the SPC-A1 cells. Knockdown of TRAF6 inhibited the migration and invasion and promoted the apoptosis of the SPC-A1 cells, but had little effect on cell proliferation and the cell cycle. In addition, siRNA induced TRAF6 knockdown caused a marked reduction in the protein expression of CD24 and CXCR4, but had little effect on MMP-1, MMP-2, MMP-9, Twist, TIMP-2 or Slug expression. The present study demonstrated that TRAF6 is upregulated in human lung cancer cells, and siRNA-induced TRAF6 knockdown inhibits the invasion of lung cancer cells and promotes apoptosis. It is suggested that TRAF6 may be a promising target for the therapy of lung cancer. PMID- 26847476 TI - Hoxa10 null animals exhibit reduced platelet biogenesis. AB - The transcription factor HOXA10 is an important regulator of myelopoiesis. Engineered over-expression of Hoxa10 in mice results in a myeloproliferative disorder that progresses to acute myeloid leukaemia (AML) over time, and in humans over-expression is associated with poor outcomes in AML. Here, we report that loss of Hoxa10 expression in mice results in reduced platelet count and platelet production, but does not affect clotting efficiency. About 40% fewer platelets were found in Hoxa10 null animals in comparison to wild type littermates. We found a nearly 50% reduction in the percentage of reticulated platelets in Hoxa10 null mice, suggesting deficient platelet production. Furthermore, Hoxa10 null animals recovered less efficiently from induced thrombocytopenia, supporting our hypothesis of defective platelet production. This also correlated with reduced colony formation potential of stem and progenitor cells seeded in megakaryocyte-enhancing conditions in vitro. Together, our results indicate that HOXA10 is important for megakaryopoiesis and platelet biogenesis. PMID- 26847477 TI - Nitidine chloride inhibits proliferation and induces apoptosis in colorectal cancer cells by suppressing the ERK signaling pathway. AB - Nitidine chloride (NC) is a natural bioactive phytochemical alkaloid that has displayed anticancer activity in various types of cancer. However, no evidence has been reported for the direct effect of NC on CRC cell proliferation and apoptosis, and the underling mechanisms to be fully elucidated. The present study aimed to investigate the influence of NC on the apoptosis and proliferation of CRC cells. The viability and proliferation of CRC cells was measured by MTT assay and a [3H] thymidine uptake assay. Apoptosis was measured using a flow cytometric apoptosis assay and TUNEL staining. The expression levels of apoptotic-regulated proteins in addition to extracellular signal-regulated kinase (ERK) were measured by western blot analysis following stimulation with NC. The results indicated that NC inhibited the proliferation of HCT116 cells in a dose- and time-dependent manner. Additionally, apoptotic induction by NC treatment was confirmed. Furthermore, NC was demonstrated to significantly upregulate the expression of Bax, p53, cleaved caspase-3 and -9 and downregulate the expression of Bcl-2. Treatment with NC reduced the phosphorylation of ERK and by using an ERK inhibitor, U0126, the roles of NC in apoptotic induction and the inhibition of proliferation were further demonstrated. These results demonstrated that NC inhibited the proliferation and induced the apoptosis of CRC cells via the ERK signaling pathway. PMID- 26847479 TI - [Cathinones use in Paris]. AB - BACKGROUND: The pattern of recreational drug use has changed over the last decade and now includes a multitude of substances sold as "research chemicals" or new psychoactive substances, "NPS". In France, synthetic cathinones emerged in 2008 (while first mentioned by the French police force in 2007 first alerts among users appeared in 2008) and have grown to be popular drugs of abuse. Under the Official Journal dated 11th June 2010, only mephedrone has been listed as narcotics but "designer drugs" have synthesized new substitute cathinones in order to avoid anti-drug laws. However, since July 2012, in France, all synthetic drugs from the cathinones family have been banned and listed as narcotics following the example of United Kingdom. Despite their recent classification and inclusion on narcotic list, they are readily available on Internet and used widely. Paris Addictovigilance Centre observed a signal of derivate cathinones abuse (21 cases over a two-year period). OBJECTIVE: Paris Addictovigilance Centre and Marmottan Hospital wanted to describe the use of cathinones in the Paris area and alert the health care community about the abuse identification and risk assessment problems of these compounds. After a review of derivated cathinone's chemical structure, pharmacology and toxicology, this article seeks to provide patricians with a clinical description and treatment's modality. RESULTS: Most users of synthetic cathinones will experience euphoria, increased energy, talkativeness, openness and increased sexual arousal. Signs and symptoms of toxicity are consistent with a sympathomimetic toxidrome. The main reasons for care access are psychiatric (hallucinations, psychotic symptoms, agitation) and addiction disorders. Somatic complications were described with various patterns of symptoms such as headache, tachycardia, confusional states, rhabdomyolysis with renal failure or serotonin syndrome. The most important fact is the apparition of the "slam" phenomenon among men who have sex with men (MSM). The "slam" is a compound of three characteristic elements: injection, sexual party and psychostimulant drug. According to users, "slam" is convenient for group sex and is used it to put them into a good mood and a disinhibition state. These compounds cause fast dependence syndrome with strong craving and prolonged psychiatric symptoms and increase infectious risk (HIV, VHC, VHB...). The cathinones family is not detected in conventional urine drug screenings. We point out the lack of confirmatory analytic testing data which remains the only way to determine the actual etiology of the clinical effects observed since drug users do not always know exactly what they took. These substances can be identified by special analyses using gas chromatography or liquid chromatography and mass spectroscopy technology. CONCLUSION: This injection drug is used in order to increase sexual desire, delay orgasm and decrease sexual inhibition and is prevalent in many studies on MSM samples. Cathinones would popularize the "slam". Harm reduction policy requires specific MSM interventions on both sexual and drug addiction networks. PMID- 26847478 TI - Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever. AB - Rift Valley Fever virus (RVFV) causes recurrent outbreaks of acute life threatening human and livestock illness in Africa and the Arabian Peninsula. No licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. A 'One Health' vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for RVFV. Here, we utilized a replication deficient chimpanzee adenovirus vaccine platform with an established human and livestock safety profile, ChAdOx1, to develop a vaccine for use against RVFV in both livestock and humans. We show that single-dose immunization with ChAdOx1 GnGc vaccine, encoding RVFV envelope glycoproteins, elicits high-titre RVFV neutralizing antibody and provides solid protection against RVFV challenge in the most susceptible natural target species of the virus-sheep, goats and cattle. In addition we demonstrate induction of RVFV-neutralizing antibody by ChAdOx1-GnGc vaccination in dromedary camels, further illustrating the potency of replication deficient chimpanzee adenovirus vaccine platforms. Thus, ChAdOx1-GnGc warrants evaluation in human clinical trials and could potentially address the unmet human and livestock vaccine needs. PMID- 26847480 TI - Healthcare Workers Emotions, Perceived Stressors and Coping Strategies During a MERS-CoV Outbreak. AB - OBJECTIVE: Healthcare workers (HCWs) are at high risk of contracting Middle East respiratory syndrome coronavirus (MERS-CoV) during an epidemic. We explored the emotions, perceived stressors, and coping strategies of healthcare workers who worked during a MERS-CoV outbreak in our hospital. DESIGN: A cross-sectional descriptive survey design. SETTING: A tertiary care hospital. PARTICIPANTS: HCWs (150) who worked in high risk areas during the April-May 2014 MERS-CoV outbreak that occurred in Jeddah, Saudi Arabia. METHODS: We developed and administered a "MERS-CoV staff questionnaire" to study participants. The questionnaire consisted of 5 sections with 72 questions. The sections evaluated hospital staffs emotions, perceived stressors, factors that reduced their stress, coping strategies, and motivators to work during future outbreaks. Responses were scored on a scale from 0-3. The varying levels of stress or effectiveness of measures were reported as mean and standard deviation, as appropriate. RESULTS: Completed questionnaires were returned by 117 (78%) of the participants. The results had many unique elements. HCWs ethical obligation to their profession pushed them to continue with their jobs. The main sentiments centered upon fear of personal safety and well-being of colleagues and family. Positive attitudes in the workplace, clinical improvement of infected colleagues, and stoppage of disease transmission among HCWs after adopting strict protective measures alleviated their fear and drove them through the epidemic. They appreciated recognition of their efforts by hospital management and expected similar acknowledgment, infection control guidance, and equipment would entice them to work during future epidemics. CONCLUSION: The MERS-CoV outbreak was a distressing time for our staff. Hospitals can enhance HCWs experiences during any future MERS-CoV outbreak by focusing on the above mentioned aspects. PMID- 26847482 TI - Trousseau's Syndrome in Cholangiocarcinoma: The Risk of Making the Diagnosis. AB - We report a case of Trousseau's syndrome with cholangiocarcinoma complicated by a fatal pulmonary embolism after liver biopsy. A 69-year-old man who presented with right upper quadrant pain was found to have portal vein thrombosis and nonspecific liver hypodensities after imaging by computerized tomography. Following four days of anticoagulation, heparin was held for percutaneous liver biopsy. After the biopsy, he developed acute hepatic failure, acute kidney injury, lactic acidemia, and expired. Autopsy revealed intrahepatic cholangiocarcinoma and a pulmonary embolism. Trousseau's syndrome with cholangiocarcinoma is rarely reported and has a poor prognosis. This case highlights a fundamental challenge in the diagnosis and early management of intrahepatic cholangiocarcinoma with hypercoagulability. Diagnostic biopsy creates an imperative to reduce post-operative bleeding risk, but this conflicts with the need to reduce thrombotic risk in a hypercoagulable state. Considering the risk of withholding anticoagulation in patients with proven or suspected cholangiocarcinoma complicated by portal vein thrombosis, physicians should consider biopsy procedures with lesser bleeding risks, such as transjugular liver biopsy or plugged percutaneous liver biopsy, to minimize interruption of anticoagulation. PMID- 26847483 TI - Anthropogenic sources of underwater sound can modify how sediment-dwelling invertebrates mediate ecosystem properties. AB - Coastal and shelf environments support high levels of biodiversity that are vital in mediating ecosystem processes, but they are also subject to noise associated with mounting levels of offshore human activity. This has the potential to alter the way in which species interact with their environment, compromising the mediation of important ecosystem properties. Here, we show that exposure to underwater broadband sound fields that resemble offshore shipping and construction activity can alter sediment-dwelling invertebrate contributions to fluid and particle transport--key processes in mediating benthic nutrient cycling. Despite high levels of intra-specific variability in physiological response, we find that changes in the behaviour of some functionally important species can be dependent on the class of broadband sound (continuous or impulsive). Our study provides evidence that exposing coastal environments to anthropogenic sound fields is likely to have much wider ecosystem consequences than are presently acknowledged. PMID- 26847484 TI - Pre-existing differences and diet-induced alterations in striatal dopamine systems of obesity-prone rats. AB - OBJECTIVE: Interactions between pre-existing differences in mesolimbic function and neuroadaptations induced by consumption of fatty, sugary foods are thought to contribute to human obesity. This study examined basal and cocaine-induced changes in striatal neurotransmitter levels without diet manipulation and D2 /D3 dopamine receptor-mediated transmission prior to and after consumption of "junk foods" in obesity-prone and obesity-resistant rats. METHODS: Microdialysis and liquid chromatography-mass spectrometry were used to determine basal and cocaine induced changes in neurotransmitter levels in real time with cocaine-induced locomotor activity. Sensitivity to the D2 /D3 dopamine receptor agonist quinpirole was examined before and after restricted junk-food exposure. Selectively bred obesity-prone and obesity-resistant rats were used. RESULTS: Cocaine-induced locomotion was greater in obesity-prone rats versus obesity resistant rats prior to diet manipulation. Basal and cocaine-induced increases in dopamine and serotonin levels did not differ. Obesity-prone rats were more sensitive to the D2 receptor-mediated effects of quinpirole, and junk-food produced modest alterations in quinpirole sensitivity in obesity-resistant rats. CONCLUSIONS: These data show that mesolimbic systems differ prior to diet manipulation in susceptible versus resistant rats, and that consumption of fatty, sugary foods produce different neuroadaptations in these populations. These differences may contribute to enhanced food craving and an inability to limit food intake in susceptible individuals. PMID- 26847486 TI - Resin composite plus connective tissue graft to treat single maxillary gingival recession associated with non-carious cervical lesion: randomized clinical trial. AB - AIM: To evaluate clinically, the aesthetics and the patient-centred parameters after the treatment of gingival recession associated with non-carious cervical lesion by connective tissue graft alone or combined with a nanofilled resin composite restoration. METHODS: Thirty-six patients presenting one Miller Class I or II gingival recessions and B+ tooth cervical defect were included. The defects were treated by either connective tissue graft (CTG: control group; n = 18) or connective tissue graft plus resin composite restoration (CTG+RC: test group; n = 18). RESULTS: The mean percentage of defect coverage was 82.16 +/- 16.1% for CTG and 73.84 +/- 19.2% for CTG+RC after 1 year (p > 0.05). Both groups presented statistically significant improvements in two aesthetics evaluations. The professional evaluation (MRES) was 7.44 +/- 2.3 for the CTG group and 7.52 +/- 2.27 for CTG+RC after 1 year, with no significant difference between the groups. The two groups presented significant reduction of dentin sensitivity (DS), it decreased from 94.4% of the sites to 44.4% in the CTG group and from 88.8% to 5.5% in the CTG+RC group. CONCLUSIONS: CTG or CTG+RC can successfully treat gingival recession associated with B+ non-carious cervical lesion, but less sensitivity may be expected with the combined approach (NCT02423473). PMID- 26847485 TI - Association of the hERG mutation with long-QT syndrome type 2, syncope and epilepsy. AB - Mutations in the human ether-a-go-go-related gene (hERG) are responsible for long QT syndrome (LQTS) type 2 (LQT2). In the present study, a heterozygous missense mutation (A561V) linked to LQT2, syncope and epilepsy was identified in the S5/pore region of the hERG protein. The mutation, A561V, was prepared and subcloned into hERG-pcDNA3.0. Mutant plasmids were co-transfected into HEK-293 cells, which stably express wild-type (WT) hERG, in order to mimic a heterozygous genotype, and the whole-cell current was recorded using a patch-clamp technique. Confocal microscopy was performed to evaluate the membrane distribution of the hERG channel protein using a green fluorescent protein tagged to the N-terminus of hERG. A561V-hERG decreased the amplitude of the WT-hERG currents in a concentration-dependent manner. In addition, A561V-hERG resulted in alterations to activation, inactivation and recovery from inactivation in the hERG protein channels. Further evaluation of hERG membrane localization indicated that the A561V-hERG mutant protein was unable to travel to the plasma membrane, which resulted in a trafficking-deficient WT-hERG protein. In conclusion, A561V-hERG exerts a potent dominant-negative effect on WT-hERG channels, resulting in decreased hERG currents and impairment of hERG membrane localization. This may partially elucidate the clinical manifestations of LQTS patients who carry the A561V mutation. PMID- 26847487 TI - Graft Utilization in the Augmentation of Large-to-Massive Rotator Cuff Repairs: A Systematic Review. AB - BACKGROUND: Current treatment options for symptomatic large-to-massive rotator cuff tears can reduce pain, but failure rates remain high. Surgeons have incorporated synthetic and biologic grafts to augment these repairs, with promising results. Multiple reviews exist that summarize these products; however, no systematic review has investigated the grafts' ability to maintain structural integrity after augmentation of large-to-massive rotator cuff repairs. PURPOSE: To systematically review and evaluate the effectiveness of grafts in the augmentation of large-to-massive rotator cuff repairs. STUDY DESIGN: Systematic review. METHODS: A comprehensive search of 4 reputable databases was completed. Inclusion criteria were (1) large-to-massive rotator cuff tear, (2) graft augmentation of primary repairs +/- primary repair control group, and (3) minimum clinical and radiologic follow-up of 12 months. Two reviewers screened the titles, abstracts, and full articles and extracted the data from eligible studies. Results were summarized into evidence tables stratified by graft origin and level of evidence. RESULTS: Ten studies fit the inclusion criteria. Allograft augmentation was functionally and structurally superior to primary repair controls, with intact repairs in 85% versus 40% of patients (P < .01). This was supported by observational study data. Xenograft augmentation failed to demonstrate superiority to primary repair controls, with worse structural healing rates (27% vs 60%; P =.11). Both comparative studies supported this finding. There have also been many reports of inflammatory reactions with xenograft use. Polypropylene patches are associated with improved structural (83% vs 59% and 49%; P < .01) and functional outcomes when compared with controls and xenograft augmentation; however, randomized data are lacking. CONCLUSION: Augmentation of large-to-massive rotator cuff repairs with human dermal allografts is associated with superior functional and structural outcome when compared with conventional primary repair. Xenograft augmentation failed to demonstrate a statistically significant difference and may be associated with worse rerupture rates and occasional severe inflammatory reactions. Polypropylene patches have initial promising results. Research in this field is limited; future researchers should continue to develop prospective, randomized controlled trials to establish clear recommendations. PMID- 26847488 TI - Graft Bending Angle at the Intra-articular Femoral Tunnel Aperture After Single Bundle Posterior Cruciate Ligament Reconstruction: Inside-Out Versus Outside-In Techniques. AB - BACKGROUND: To date, no in vivo 3-dimensional computed tomography (3D-CT) studies have compared graft bending angles at the femoral tunnel aperture and femoral tunnel length in patients who underwent posterior cruciate ligament (PCL) reconstruction with outside-in (OI) and inside-out (IO) techniques. PURPOSE/HYPOTHESIS: This study used in vivo 3D-CT analysis to compare graft bending angles at the femoral tunnel aperture and femoral tunnel lengths after OI and IO femoral drilling techniques in single-bundle PCL reconstruction. It was hypothesized that the graft bending angle at the femoral tunnel aperture would be less acute with the OI compared with the IO technique, with no difference in femoral tunnel lengths. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Immediate postoperative in vivo 3D-CT and curved planar reformation were used to assess the graft bending angles and femoral tunnel lengths in the sagittal, axial, and coronal planes in 67 patients who underwent single-bundle PCL reconstruction with the OI (n = 37) and IO (n = 30) techniques. RESULTS: The mean graft bending angles on the sagittal and axial planes were 8.2 degrees more acute (23.5 degrees vs 15.3 degrees , P = .011) and 5.3 degrees more acute (49.0 degrees vs 43.7 degrees , P = .013), respectively, with the IO compared with the OI technique, but the difference in the coronal plane was not statistically significant (25.3 degrees vs 24.8 degrees , P = .623). Femoral tunnel length was similar in the 2 groups. CONCLUSION: The graft bending angles in single-bundle PCL reconstruction were more acute in the sagittal and axial planes with the IO compared with the OI technique, but there was no difference in the coronal plane. In addition, femoral tunnel lengths did not differ significantly in patients who underwent OI and IO single-bundle PCL reconstructions. Although further biomechanical studies are needed to evaluate the effect on graft failure of a <10 degrees difference in graft bending angle, the small magnitude of this difference would likely have little adverse effect on graft survival. PMID- 26847489 TI - CCR4 frameshift mutation identifies a distinct group of adult T cell leukaemia/lymphoma with poor prognosis. AB - Adult T cell leukaemia/lymphoma (ATLL) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next-generation sequencing-based comprehensive mutation studies have revealed recurrent somatic CCR4 mutations in ATLL, although clinicopathological findings associated with CCR4 mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL, were subjected to CCR4 mutation analysis. This sequence analysis identified mutations in 27% (30/113) of cases of ATLL and 9% (4/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS) and frameshift (FS) mutations. No significant differences in clinicopathological findings were observed between ATLL cases stratified by presence of CCR4 mutation. All ATLL cases with CCR4 mutations exhibited cell-surface CCR4 positivity. Semi-quantitative CCR4 protein analysis of immunohistochemical sections revealed higher CCR4 expression in cases with NS mutations of CCR4 than in cases with wild-type (WT) CCR4. Furthermore, among ATLL cases, FS mutation was significantly associated with a poor prognosis, compared with NS mutation and WT CCR4. These results suggest that CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology. PMID- 26847490 TI - Discovery and expression of 3 siglecs-like in Oreochromis niloticus neutrophil, and their interaction with group B streptococcal sialylated capsular polysaccharides. AB - Sialic acid - binding immunoglobulin - like lectins (Siglecs) are members of the largest superfamily of immune receptors; they recognize sialic acid and are mainly expressed in immune cells. Studies on mammals indicate that Streptococcus agalactiae (GBS) evade immune reactions by interacting with the host immune cells via the sialic acid of sialylated capsular polysaccharides. However, it is currently unknown if fish-derived GBS can interact with Siglecs to evade host immunity. In this study, we examined the binding of FITC-GBS with neutrophils to determine the presence of receptors that binds with GBS. Furthermore, 3 Siglec like genes, (OnSiglec-1-like/-4b-like/-14-like) from the neutrophils cDNA were screened by PCR. All the genes had specific domains (immunostimulation and immunosuppression domains), conserved amino acid residues, and sialic acid polysaccharide binding sites that are found in mammalian Siglecs. Flow cytometry of Siglecs-like/COS-7 cells and ELISA of Siglecs/Ex-Fc fusion proteins confirmed that 3 Siglecs-like have high binding activity with GBS. Erythrocytes adhesion assays and sialylated glycans binding assay confirmed that 3 Siglecs-like bind to sialic acid polysaccharides. Siglecs-like had high expression levels in the spleen, gill, and kidney in Oreochromis niloticus by qPCR. After experimental infection, Siglec-1-like/-14-like showed a significant upregulated initially and later downregulated in liver, spleen, kidney, and gill. However, Siglec-4b-like was downregulated in most tissues, except that in liver. The results indicate that 3 OnSiglecs-like may recognize GBS sialylated capsular polysaccharides. GBS infections led to significant changes in Siglecs-like expression in immune related tissues. However, immunostimulation or immunosuppression via the recognition of GBS by different Siglecs-like molecules requires additional studies. PMID- 26847491 TI - Evaluation of Speech Amplification Devices in Parkinson's Disease. AB - PURPOSE: The purpose of this study was to evaluate the efficacy of selected speech amplification devices in individuals with hypophonia and idiopathic Parkinson's disease (PD). METHOD: This study compared the effectiveness of seven devices (ADDvox, BoomVox, ChatterVox, Oticon Amigo, SoniVox, Spokeman, and Voicette) to unamplified speech for 11 participants with PD during conversation in 65-dB SPL multitalker noise, using experience ratings collected from participant questionnaires and speech performance measures (i.e., speech-to-noise ratio [SNR], speech intensity, and intelligibility) obtained from audio recordings. RESULTS: Compared with unamplified speech, device use increased SNR by 1.07-4.73 dB SPL and speech intensity by 1.1-5.1 dB SPL, and it significantly increased transcribed intelligibility from 13.8% to 58.9%. In addition, the type of device used significantly affected speech performance measures (e.g., BoomVox was significantly higher than most of the other devices for SNR, speech intensity, and intelligibility). However, experience ratings did not always correspond to performance measures. CONCLUSIONS: This study found preliminary evidence of improved speech performance with device use for individuals with PD. A tentative hierarchy is suggested for device recommendations. Future research is needed to determine which measures will predict long-term device acceptance in PD. PMID- 26847492 TI - Retinal and choroidal expression of BMP-2 in lens-induced myopia and recovery from myopia in guinea pigs. AB - The present study investigated the retinal and choroidal expression of bone morphogenetic protein-2 (BMP-2) in myopia and in myopia recovery in a guinea pig model. For this investigation, two groups of guinea pigs, lens-induced myopia and recovery from myopia, were used, and defocused myopia was induced the guinea pigs wearing -4.00 D lenses on the right eyes for 3 weeks, with the left eyes serving as the contralateral. In the following week, the lenses of the guinea pigs in the recovery group were removed, and the refractive power and axial length were measured. The expression of BMP-2 in the eyeballs was observed using immunohistochemistry and analyzed using Western blot analysis. After 3 weeks, the eyes acquired relative myopia and longer axial lengths in the two groups of guinea pigs. After 1 week without lenses in the recovery group, the myopia and axial lengths regressed. Immunofluorescence staining showed that BMP-2 was expressed in the posterior retina, RPE, choroid and sclera. The expression of BMP 2 decreased in the myopic retina of the guinea pigs. Following the regression of myopia in the recovery group, no difference in the expression of BMP-2 was observed between the recovered treated eyes and the contralateral eyes. The choroidal expression level of BMP-2 in the treated eyes showed no significant changes in either group. Therefore, BMP-2 may be involved in the development of myopia, however, it does not have a primary role in the retinal and choroidal signals regulating scleral remodeling. PMID- 26847481 TI - Hypoxia: The Force that Drives Chronic Kidney Disease. AB - In the United States the prevalence of end-stage renal disease (ESRD) reached epidemic proportions in 2012 with over 600,000 patients being treated. The rates of ESRD among the elderly are disproportionally high. Consequently, as life expectancy increases and the baby-boom generation reaches retirement age, the already heavy burden imposed by ESRD on the US health care system is set to increase dramatically. ESRD represents the terminal stage of chronic kidney disease (CKD). A large body of evidence indicating that CKD is driven by renal tissue hypoxia has led to the development of therapeutic strategies that increase kidney oxygenation and the contention that chronic hypoxia is the final common pathway to end-stage renal failure. Numerous studies have demonstrated that one of the most potent means by which hypoxic conditions within the kidney produce CKD is by inducing a sustained inflammatory attack by infiltrating leukocytes. Indispensable to this attack is the acquisition by leukocytes of an adhesive phenotype. It was thought that this process resulted exclusively from leukocytes responding to cytokines released from ischemic renal endothelium. However, recently it has been demonstrated that leukocytes also become activated independent of the hypoxic response of endothelial cells. It was found that this endothelium-independent mechanism involves leukocytes directly sensing hypoxia and responding by transcriptional induction of the genes that encode the beta2 integrin family of adhesion molecules. This induction likely maintains the long term inflammation by which hypoxia drives the pathogenesis of CKD. Consequently, targeting these transcriptional mechanisms would appear to represent a promising new therapeutic strategy. PMID- 26847493 TI - Anthropogenic noise increases fish mortality by predation. AB - Noise-generating human activities affect hearing, communication and movement in terrestrial and aquatic animals, but direct evidence for impacts on survival is rare. We examined effects of motorboat noise on post-settlement survival and physiology of a prey fish species and its performance when exposed to predators. Both playback of motorboat noise and direct disturbance by motorboats elevated metabolic rate in Ambon damselfish (Pomacentrus amboinensis), which when stressed by motorboat noise responded less often and less rapidly to simulated predatory strikes. Prey were captured more readily by their natural predator (dusky dottyback, Pseudochromis fuscus) during exposure to motorboat noise compared with ambient conditions, and more than twice as many prey were consumed by the predator in field experiments when motorboats were passing. Our study suggests that a common source of noise in the marine environment has the potential to impact fish demography, highlighting the need to include anthropogenic noise in management plans. PMID- 26847494 TI - The Effect of Sterilization Methods on the Structural and Chemical Properties of Fibrin Microthread Scaffolds. AB - A challenge for the design of scaffolds in tissue engineering is to determine a terminal sterilization method that will retain the structural and biochemical properties of the materials. Since commonly used heat and ionizing energy-based sterilization methods have been shown to alter the material properties of protein based scaffolds, the effects of ethanol and ethylene oxide (EtO) sterilization on the cellular compatibility and the structural, chemical, and mechanical properties of uncrosslinked, UV crosslinked, or 1-ethyl-3-(3 dimethylaminopropyl)carbodiimide (EDC) crosslinked fibrin microthreads in neutral (EDCn) or acidic (EDCa) buffers are evaluated. EtO sterilization significantly reduces the tensile strength of uncrosslinked microthreads. Surface chemistry analyses show that EtO sterilization induces alkylation of EDCa microthreads leading to a significant reduction in myoblast attachment. The material properties of EDCn microthreads do not appear to be affected by the sterilization method. These results significantly enhance the understanding of how sterilization or crosslinking techniques affect the material properties of protein scaffolds. PMID- 26847496 TI - Are informational videos good for pediatric patients? PMID- 26847495 TI - [Hypertensive crisis and sudden change of vision in young patients]. AB - The sudden change in vision is a medical emergency that must be evaluated immediately to rule out important institutions as systemic vasculitis or ischemic stroke. Its association with hypertensive crisis makes it necessary to rule out accelerated-malignant hypertension, which is accompanied by other retinal disorders (exudates and hemorrhages) and adrenal involvement. Nonarteritic anterior ischemic optic neuropathy (AION) is another entity to consider, as is it not uncommon in the young (12.7% in a series of 848 cases). Its association with hypertension has been described in 32% of cases. PMID- 26847497 TI - Characteristics of actinic prurigo in Scotland: 24 cases seen between 2001 and 2015. PMID- 26847498 TI - Microleakage of 4 post-luting cements evaluated by the computerized fluid filtration method. AB - PURPOSE: The aim of this study was to evaluate the microleakage of 4 fiber post luting systems using the computerized fluid filtration method. METHODS: 60 extracted human mandibular permanent premolar teeth were used for the study. The teeth were instrumented with Hedstroem files up to size 60, post spaces were prepared and then Unicore fiber posts were cemented using 4 luting systems. Group1: Duolink, Group 2: Resinomer, Group 3: Fuji Plus, Group 4: Multilink Sprint, Group 5: Positive Control, and Group 6: Negative Control. The samples were stored in distilled water for 2 weeks and then microleakage was evaluated. Data were analyzed with 1 way-ANOVA and Dunett T3 tests (P<.05). Groups 2 and 3 significantly exhibited higher microleakage values than groups 1 and 4 (P<.05). RESULTS: Resin cements used with total etch-bonding systems demonstrated lower microleakage values than the other cements. CONCLUSIONS: Reduction of steps in dentin conditioning of resin luting cements may have a promoting effect on microleakage. PMID- 26847499 TI - Systemic inflammatory cytokine analysis to monitor biomaterial augmented tissue healing. AB - PURPOSE: Hernias can be repaired by reinforcement of damaged fascia using biomaterials to provide stabilisation. Repair materials are usually porous, through which cells infiltrate, proliferate and secrete ECM. Their efficacy relies on good tissue integration and resolution of host defence mechanisms. Therefore, understanding the dynamics by which biomaterials interact with tissue will provide knowledge to advance prosthesis design. Furthermore, determining host response in real time would provide significant advantage both clinically and scientifically over the current terminal process of histology. METHODS: 3 materials comprising synthetic and composite (synthetic materials hybridised with a resorbable biologic component) meshes were implanted into a rat full-thickness abdominal wall excision model. Their efficacy was evaluated using histopathology whilst also monitoring systemic concentrations of cytokines associated with inflammation and wound healing to predict material outcome over 12 weeks. RESULTS: The noncomposite material (polyester) and Material B (polypropylene mesh with oligocaprone film and polydioxanone glue) stimulated the largest degree of adhesion from the 3 materials tested, although after 28 days adhesions were stronger to Material B. Histologically, all 3 materials integrated well with abdominal musculature and infiltrated completely with cells. CONCLUSIONS: Analysis of systemic inflammation biomarkers confirmed inflammation elicited by surgeries and meshes irrespective of their composition. However, at an early postoperative endpoint (i.e., 1 week), some biomarkers, namely, IL-18 and RANTES, appeared to discriminate the noncomposite mesh from the composite materials, although in this study all materials successfully repaired the defects without recurrence or external indicators of postoperative chronic pain. PMID- 26847500 TI - Simulation of acute haemodynamic outcomes of the surgical strategies for the right ventricular failure treatment in pediatric LVAD. AB - BACKGROUND: Right ventricular failure (RVF) is one of the major complications during LVAD. Apart from drug therapy, the most reliable option is the implantation of RVAD. However, BIVAD have a poor prognosis and increased complications. Experiments have been conducted on alternative approaches, such as the creation of an atrial septal defect (ASD), a cavo-aortic shunt (CAS) including the LVAD and a cavo-pulmonary connection (CPC). This work aims at realizing a lumped parameter model (LPM) to compare the acute hemodynamic effects of ASD, CPC, CAS, RVAD in LVAD pediatric patients with RVF. METHODS: Data of 5 pediatric patients undergoing LVAD were retrospectively collected to reproduce patients baseline hemodynamics with the LPM. The effects of continuous flow LVAD implantation complicated by RVF was simulated and then the effects of ASD, CPC, CAS and RVAD treatments were simulated for each patient. RESULTS: The model successfully reproduced patients' baseline and the hemodynamic effects of the surgical strategies. Simulating the different surgical strategies, an unloading of the right ventricle and an increment of left ventricular preload were observed with an improvement of the hemodynamics (total cardiac output: ASD +15%, CPC +10%, CAS +70% RVAD +20%; right ventricular external work: ASD -19%, CPC -46%, CAS -76%, RVAD -32%; left ventricular external work: ASD +12%, CPC +28%, RVAD +64%). CONCLUSIONS: The use of numerical model could offer an additional support for clinical decision-making, also potentially reducing animal experiments, to compare the outcome of different surgical strategies to treat RVF in LVAD. PMID- 26847501 TI - Veno-veno-arterial ECMO support for acute myocarditis combined with ARDS: a case report. AB - BACKGROUND: In patients who developed a combined situation of severe acute respiratory distress syndrome with refractory hypoxemia and acute cardiac failure with circulatory collapse, traditional veno-venous or veno-arterial extracorporeal membrane oxygenation approach alone may not be sufficient enough to maintain both an acceptable range of gas exchange and a hemodynamic stability. CASE REPORT: A 27-year-old male patient was suffering from severe acute respiratory distress syndrome caused by community-acquired pneumonia and acute myocarditis with circulatory shock. After mechanical ventilation for respiratory support, he was in a persistently refractory shock state. Veno-veno-arterial mode of extracorporeal membrane oxygenation was thus applied to provide both respiratory and circulatory support simultaneously, with good success. DISCUSSION: Modifying to a veno-veno-arterial mode can be another alternative strategy in a combined situation of refractory respiratory and cardiac failure, thus providing not only respiratory support but also circulatory support. In veno veno-arterial mode, the returning circuit from the pump was divided with a Y connector into 2 reinfusion circuits; each reinfusion circuit was connected to the contralateral side femoral vein and artery, respectively. The distribution of reinfusion flow was adjusted depending on the patient's cardiopulmonary status. CONCLUSIONS: Although there is no consensus about the veno-veno-arterial mode of extracorporeal membrane oxygenation, this combined mode can be helpful in patients with acute refractory respiratory and cardiac failure, as shown in the present case. We need further experience and improvements in the circuit system used in the veno-veno-arterial mode of ECMO. PMID- 26847503 TI - Notch-Induced Expression of FZD7 Requires Noncanonical NOTCH3 Signaling in Human Breast Epithelial Cells. AB - The evolutionarily conserved Notch and Wnt signaling pathways have demonstrated roles in normal mammary gland development and in breast carcinogenesis. We previously reported that in human mammary gland, signaling through NOTCH3 alone regulates the commitment of the undifferentiated bipotential progenitors to the luminal cell fate, indicating that NOTCH3 may regulate the expression of unique genes apart from the other Notch receptors. In this study, we used gain of function and loss of function experiments and found that a Wnt signaling receptor, Frizzled7 (FZD7), is a unique and nonredundant target of NOTCH3 in human breast epithelial cells. Interestingly, neither the constitutively active forms of NOTCH1-2, 4 nor loss of expression of these receptors were able to alter expression of FZD7 in human breast epithelial cells. We further show that FZD7 expressing cells are found more frequently in the luminal progenitor-enriched subpopulation of cells obtained from breast reduction samples compared with the undifferentiated bipotent progenitors. Also, we show that NOTCH3-induced expression of FZD7 occurs in the absence of CSL (CBF1-Suppressor of Hairless-Lag 1). Our data suggest that noncanonical Notch signaling through NOTCH3 could modulate Wnt signaling via FZD7 and in this way, might be involved in luminal cell differentiation. PMID- 26847502 TI - Reassessing ecdysteroidogenic cells from the cell membrane receptors' perspective. AB - Ecdysteroids secreted by the prothoracic gland (PG) cells of insects control the developmental timing of their immature life stages. These cells have been historically considered as carrying out a single function in insects, namely the biochemical conversion of cholesterol to ecdysteroids and their secretion. A growing body of evidence shows that PG cells receive multiple cues during insect development so we tested the hypothesis that they carry out more than just one function in insects. We characterised the molecular nature and developmental profiles of cell membrane receptors in PG cells of Bombyx mori during the final larval stage and determined what receptors decode nutritional, developmental and physiological signals. Through iterative approaches we identified a complex repertoire of cell membrane receptors that are expressed in intricate patterns and activate previously unidentified signal transduction cascades in PG cells. The expression patterns of some of these receptors explain precisely the mechanisms that are known to control ecdysteroidogenesis. However, the presence of receptors for the notch, hedgehog and wingless signalling pathways and the expression of innate immunity-related receptors such as phagocytosis receptors, receptors for microbial ligands and Toll-like receptors call for a re-evaluation of the role these cells play in insects. PMID- 26847504 TI - Recommandations pour la prise en charge de l'infection par le virus de l'hepatite C chez les usagers de drogues par injection. PMID- 26847505 TI - Successful One Stage Surgical Removal of Intravenous Leiomyomatosis with On Pump Beating Heart Technique. AB - An intravenous leiomyomatoma is a rare benign smooth muscle tumour originating from myometrial veins. Surgical resection is the best treatment for intracardiac extension of intravenous leiomyoma. Here we present a very rare case of intravascular and intracardiac leiomyomatosis. We successfully performed one stage surgery to remove the leiomyomatosis with beating heart under cardiopulmonary bypass. PMID- 26847507 TI - High-Quality Metal-Organic Framework Ultrathin Films for Electronically Active Interfaces. AB - Currently available methodologies arguably lack the exquisite control required for producing metal-organic framework (MOF) thin films of sufficient quality for electronic applications. By directing MOF transfer with self-assembled monolayers (SAMs), we achieve very smooth, homogeneous, highly oriented, ultrathin films across millimeter-scale areas that display moderate conductivity likely due to electron hopping. Here, the SAM is key for directing the transfer thereby enlarging the number and nature of the substrates of choice. We have exploited this versatility to evolve from deposition onto standard Si and Au to nonconventional substrates such as ferromagnetic Permalloy. We believe that this strategy might be useful for the integration of MOFs as active interfaces in electronic devices. PMID- 26847506 TI - Gliptin-mediated neuroprotection against stroke requires chronic pretreatment and is independent of glucagon-like peptide-1 receptor. AB - Gliptins are anti-type 2 diabetes (T2D) drugs that regulate glycaemia by preventing endogenous glucagon-like peptide-1 (GLP-1) degradation. Chronically administered gliptins before experimental stroke can also induce neuroprotection, and this effect is potentially relevant for reducing brain damage in patients with T2D and high risk of stroke. It is not known, however, whether acute gliptin treatment after stroke (mimicking a post-hospitalization treatment) is neuroprotective or whether gliptin-mediated neuroprotection occurs via GLP-1 receptor (GLP-1R) activation. To answer these two questions, wild-type and glp 1r(-/-) mice were subjected to transient middle cerebral artery occlusion (MCAO). Linagliptin was administered acutely (50 mg/kg intravenously), at MCAO time or chronically (10 mg/kg orally) for 4 weeks before and 3 weeks after MCAO. Neuroprotection was assessed by stroke volume measurement and quantification of NeuN-positive surviving neurons. Plasma/brain GLP-1 levels and dipeptidyl peptidase-4 activity were also measured. The results show that the linagliptin mediated neuroprotection against stroke requires chronic pretreatment and does not occur via GLP-1R. The findings provide essential new knowledge with regard to the potential clinical use of gliptins against stroke, as well as a strong impetus to identify gliptin-mediated neuroprotective mechanisms. PMID- 26847508 TI - Le Fort I Osteotomy. PMID- 26847509 TI - Le Fort III and Le Fort II Osteotomies. PMID- 26847510 TI - The Bilateral Sagittal Split Mandibular Ramus Osteotomy. PMID- 26847511 TI - Intraoral Vertical Ramus Osteotomy Procedure and Technique. PMID- 26847512 TI - Implications of Sequencing in Simultaneous Maxillary and Mandibular Orthognathic Surgery. PMID- 26847513 TI - Computer-Assisted Surgical Simulation for Concomitant Temporomandibular Joint Custom-Fitted Total Joint Reconstruction and Orthognathic Surgery. PMID- 26847514 TI - Surgically Assisted Maxillary Expansion. PMID- 26847515 TI - Genioplasty. PMID- 26847516 TI - Techniques in Orthognathic Surgery. PMID- 26847517 TI - Participation in research bronchoscopy: a literature review. AB - Bronchoscopy is the preferred method for collecting biological samples from the lower airways of subjects in clinical research. However, ensuring participation in clinical research can be challenging when the research includes an invasive procedure. For this report we reviewed the literature to look for information on participation in research bronchoscopy studies to better design our own study, the Bergen COPD Microbiome study (MicroCOPD). We performed a systematic literature search on participation in research bronchoscopy studies in February 2014 using the search engines of PubMed and EMBASE. The literature search resulted in seven relevant papers. Motivation was an end point in six of the seven papers, but reasons for declining participation and recruitment strategies also seemed important. Human subjects participate in research bronchoscopy studies for personal benefit and altruistic reasons. Inconvenience associated with research, in addition to fear of procedures, is considered a barrier. Radio, especially news stations, generated the most inquiries for a clinical study involving bronchoscopy. There is a lack of information on participation in research bronchoscopy studies in the literature. A bronchoscopy study has been initiated at Haukeland University Hospital, Bergen, Norway, to examine the role of the microbiome in COPD, and participation will be explored as a substudy. PMID- 26847518 TI - The effect of targeted decolonization on methicillin-resistant Staphylococcus aureus colonization or infection in a surgical intensive care unit. AB - BACKGROUND: The effect of decolonization on the control of methicillin-resistant Staphylococcus aureus (MRSA) may differ depending on intensive care unit (ICU) settings and the prevalence of antiseptic resistance in MRSA. METHODS: This study was conducted in a 14-bed surgical ICU over a 40-month period. The baseline period featured active surveillance for MRSA and institution of contact precautions. MRSA decolonization via chlorhexidine baths and intranasal mupirocin was implemented during a subsequent 20-month intervention period. Pre-post and interrupted time series analysis were used to evaluate changes in the clinical incidence of hospital-acquired MRSA colonization or infection. MRSA isolates were tested for the presence of qacA/B genes and mupirocin resistance. RESULTS: In pre post analysis, the clinical incidence of MRSA significantly decreased by 61.6% after implementation of decolonization (P < .001). Meanwhile, interrupted time series analysis showed decreases in both the level (beta = -0.686; P = .210) and trend (beta = -0.011; P = .819) of clinical MRSA incidence, but these changes were not statistically significant. Of 169 MRSA isolates, 64 (37.8%) carried the qacA/B genes, and 22 (13.0%) showed either low- (n = 20) or high-level (n = 2) resistance to mupirocin. Low-level mupirocin resistance significantly increased from 0%-19.4% during the study period. CONCLUSION: Although decolonization using antiseptic agents was helpful to decrease hospital-acquired MRSA rates, the emergence of antiseptic resistance should be monitored. PMID- 26847519 TI - Evaluating the suitability of maggot meal as a partial substitute of soya bean on the productive traits, digestibility indices and organoleptic properties of broiler meat. AB - This study was conducted to replace soya bean meal with maggot meal at difference percentages. A total of 120 one-day-old broiler chicks were divided into four groups. Four diets were formulated with maggot meal to replace soya bean meal at the rate of 0%, 10%, 20% and 30% designated as A, B, C and D respectively. Feed and water were offered ad libitum during the study which lasted for 28 days. Feed intake decreased significantly in treated groups while body weight, Feed conversion ratio and dressing percentage increased significantly in group D. Apparent metabolizable energy increased significantly in the group fed 30% maggot meal; however, no significant difference was found in dry matter, crude protein, crude fibre, ether extract, ash and nitrogen free extract between the control and treated groups. The result of sensory evaluation revealed that tenderness and juiciness increased significantly in group C and B respectively. The colour and flavour were most accepted in group B and C. The results indicate that replacement of soya bean meal at the rate of 30% in broiler feed produced most favourable results. PMID- 26847521 TI - Effect of a solar Fered-Fenton system using a recirculation reactor on biologically treated landfill leachate. AB - The effects of electrochemical oxidation (EO), Fered-Fenton and solar Fered Fenton processes using a recirculation flow system containing an electrochemical cell and a solar photo-reactor on biochemically treated landfill leachate were investigated. The most successful method was solar Fered-Fenton which achieved 66.5% COD removal after 120min treatment utilizing the optimum operating conditions of 47mM H2O2, 0.29mM Fe(2+), pH0 of 3.0 and a current density of 60mA/cm(2). The generation of hydroxyl radicals (OH) are mainly from Fered-Fenton process, which is enhanced by the introduction of renewable solar energy. Moreover, Fe(2+)/chlorine and UV/chlorine processes taking place in this system also result in additional production of OH due to the relatively high concentration of chloride ions contained in the leachate. The energy consumption was 74.5kWh/kg COD and the current efficiency was 36.4% for 2h treatment. In addition, the molecular weight (MW) distribution analysis and PARAFAC analysis of excitation emission matrix (EEM) fluorescence spectroscopy for different leachate samples indicated that the organics in the leachate were significantly degraded into either small molecular weight species or inorganics. PMID- 26847522 TI - Heavy metal removal from multicomponent system by sulfate reducing bacteria: Mechanism and cell surface characterization. AB - This study evaluated the combined effect of Cd(II), Cu(II), Ni(II), Fe(III), Pb(II) and Zn(II) on each other removal by anaerobic biomass under sulfate reducing condition. Statistically valid Plackett-Burman design of experiments was employed to carry out this mixture study. The results obtained showed a maximum removal of Cu(II) (98.9%), followed by Ni(II) (97%), Cd(II) (94.8%), Zn(II) (94.6%), Pb(II) (94.4%) and Fe(III) (93.9%). Analysis of variance (ANOVA) of the sulfate and chemical oxygen demand (COD) reduction revealed that the effect due to copper was highly significant (P value<0.05) on sulfate and COD removal. To establish the role of sulfate reducing bacteria (SRB) in the metal removal process, surface morphology and composition of the metal loaded biomass were analyzed by transmission electron microscopy (TEM) equipped with energy dispersive spectroscopy (EDS) and by field emission scanning electron microscopy (FESEM) integrated with energy dispersive X-ray spectroscopy (EDX). The results obtained revealed that the metal precipitates are associated with the outer and inner cell surface of the SRB as a result of the sulfide generated by SRB. PMID- 26847520 TI - miR-203 inhibits proliferation and self-renewal of leukemia stem cells by targeting survivin and Bmi-1. AB - Drug resistance is one of the leading causes of failed cancer therapy in the treatment of acute myeloid leukemia. Although the mechanisms of resistance are poorly understood, they may be related to the presence of leukemia stem cells (LSCs). Down-regulation of the miR-203 reportedly contributes to oncogenesis and chemo-resistance in multiple cancers. We found that miR-203 expression was down regulated in CD34 + AML cells as compared with CD34- cells isolated from patients as well as in LSC-enriched (CD34 + CD38-) cell lines KG-1a or MOLM13. Additionally, re-expression of miR-203 led to decreased cell proliferation, self renewal, and sphere formation in LSCs. Moreover, miR-203 was found to directly target the 3'un-translated regions of survivin and Bmi-1 mRNAs affecting proliferation and self-renewal in LSCs. In this study, we identified a novel miR 203/survivin/Bmi-1 axis involved in the regulation of biological properties of LSCs. This axis may represent a new therapeutic target for acute myeloid leukemia and a potential prognosis/diagnostic marker for LSCs therapy. PMID- 26847523 TI - Medical indication regarding life-sustaining treatment for children: Focus groups with clinicians. AB - BACKGROUND: Decisions about medical indication are a relevant problem in pediatrics. Difficulties arise from the high prognostic uncertainty, the decisional incapacity of many children, the importance of the family, and conflicts with parents. The objectivity of judgments about medical indication has been questioned. Yet, little is known about the factors pediatricians actually include in their decisions. AIM: Our aims were to investigate which factors pediatricians apply in deciding about medical indication, and how they manage conflicts with parents. DESIGN: We performed a qualitative focus group study with experienced pediatricians. The transcripts were subjected to qualitative content analysis. SETTING/PARTICIPANTS: We conducted three focus groups with pediatricians from different specialties caring for severely ill children/adolescents. They discussed life-sustaining treatment in two case scenarios that varied according to diagnosis, age, and gender. RESULTS: The decisions about medical indication were based on considerations relating to the individual patient, to the family, and to other patients. Individual patient factors included clinical aspects and benefit-burden considerations. Physicians' individual views and feelings influenced their decision-making. Different factors were applied or weighed differently in the two cases. In case of conflict with parents, physicians preferred solutions aimed at establishing consensus. CONCLUSION: The pediatricians defined medical indication on a case-by-case basis and were influenced by emotional reasoning. In contrast to prevailing ethico legal principles, they included the interests of other persons in their decisions. Decision-making strategies should incorporate explicit discussions of social aspects and physicians' feelings to improve the transparency of the decision-making process and reduce bias. PMID- 26847524 TI - Patient and caregiver perspectives on managing pain in advanced cancer: A qualitative longitudinal study. AB - BACKGROUND: Despite advances in treatment of pain in advanced cancer, it remains a major source of suffering with adverse effects on patients' life quality. There is increasing understanding of its multi-dimensional nature and the variable responsiveness of medication to complex pain. Less clear is how patients and their caregivers respond to and manage pain complexity. AIM: To explore patients' and carers' experiences of advanced cancer pain and the processes that they engage in to manage pain. DESIGN: Qualitative study employing face-to-face interviews at two time points and audio diaries. Data were analysed using grounded theory strategies. SETTING/PARTICIPANTS: Purposive sample of 21 advanced cancer patients and 16 carers from oncology outpatients in a tertiary cancer centre and a hospice. RESULTS: Three distinct patterns of pain were discerned in patients' accounts, distinguishable in terms of complexity, severity, transiency and degree of perceived control over pain. Pain was dynamic reflecting changes in the disease process, access to and effectiveness of pain relief. For patients and carers, neither pain relief nor expertise in pain management is secured once and for all. The main drivers of help-seeking and action by patients to manage pain were the sensory experiences of pain and meaning attached to it, not beliefs about analgesia. CONCLUSION: The complex and dynamic nature of pain and how it was understood shaped help-seeking and pain management. Variable effectiveness of pain relief for different pain types were challenging for patients and professionals in achieving relief. PMID- 26847525 TI - Progress and divergence in palliative care education for medical students: A comparative survey of UK course structure, content, delivery, contact with patients and assessment of learning. AB - BACKGROUND: Effective undergraduate education is required to enable newly qualified doctors to safely care for patients with palliative care and end-of life needs. The status of palliative care teaching for UK medical students is unknown. AIM: To investigate palliative care training at UK medical schools and compare with data collected in 2000. DESIGN: An anonymised, web-based multifactorial questionnaire. SETTINGS/PARTICIPANTS: Results were obtained from palliative care course organisers at all 30 medical schools in 2013 and compared with 23 medical schools (24 programmes) in 2000. RESULTS: All continue to deliver mandatory teaching on 'last days of life, death and bereavement'. Time devoted to palliative care teaching time varied (2000: 6-100 h, mean 20 h; 2013: 7-98 h, mean 36 h, median 25 h). Current palliative care teaching is more integrated. There was little change in core topics and teaching methods. New features include 'involvement in clinical areas', participation of patient and carers and attendance at multidisciplinary team meetings. Hospice visits are offered (22/24 (92%) vs 27/30 (90%)) although they do not always involve patient contact. There has been an increase in students' assessments (2000: 6/24, 25% vs 2013: 25/30, 83%) using a mixture of formative and summative methods. Some course organisers lack an overview of what is delivered locally. CONCLUSION: Undergraduate palliative care training continues to evolve with greater integration, increased teaching, new delivery methods and wider assessment. There is a trend towards increased patient contact and clinical involvement. A minority of medical schools offer limited teaching and patient contact which could impact on the delivery of safe palliative care by newly qualified doctors. PMID- 26847526 TI - Advance care planning in motor neuron disease: A qualitative study of caregiver perspectives. AB - BACKGROUND: Motor neuron disease is a fatal disease, characterised by progressive loss of motor function, often associated with cognitive deterioration and, in some, the development of frontotemporal dementia. Life-sustaining technologies are available (e.g. non-invasive ventilation and enteral nutrition) but may compromise quality of life for some patients. Timely commencement of 'Advance Care Planning' enables patients to participate in future care choices; however, this approach has rarely been explored in motor neuron disease. AIM: We aimed to investigate caregiver perspectives on the acceptability and impact of advance care planning, documented in a letter format, for patients with motor neuron disease and caregivers. DESIGN: This is a qualitative cross-sectional study. Data were analysed by a narrative synthesis approach. PARTICIPANTS AND SETTING: Structured interviews were held with 18 former caregivers of deceased patients with motor neuron disease. A total of 10 patients had created a disease-specific advanced directive, 'Letter of Future Care', and 8 had not. RESULTS: A total of four global themes emerged: Readiness for death, Empowerment, Connections and Clarifying decisions and choices. Many felt the letter of future care was or would be beneficial, engendering autonomy and respect for patients, easing difficult decision-making and enhancing communication within families. However, individuals' 'readiness' to accept encroaching death would influence uptake. Appropriate timing to commence advance care planning may depend on case-based clinical and personal characteristics. CONCLUSION: Advance care planning can assist patients to achieve a sense of control and 'peace of mind' and facilitates important family discussion. However, the timing and style of its introduction needs to be approached sensitively. Tools and strategies for increasing the efficacy of advance care planning for motor neuron disease should be evaluated and implemented. PMID- 26847527 TI - Physical Therapy Treatment of Impaired Chest Mobility in Patients with Airway Sensory Hyperreactivity. AB - BACKGROUND AND PURPOSE: In sensory hyperreactivity (SHR), patients have symptoms from the airways and the chest induced by environmental irritants like scenting products and cigarette smoke. They are characterized by increased cough reaction to inhaled capsaicin compared with healthy controls. Lung function tests are normal, and asthma medications have no or little effect. In a recent published article, patients with SHR were found to have impaired chest mobility and increased pain sensitivity. The purpose of this study was to evaluate if a physiotherapeutic intervention can increase chest mobility in SHR, influence these patients' symptoms and reduce capsaicin cough sensitivity. METHODS: Forty one SHR patients were initially randomized in to groups, one for training and one for symptom registration in this controlled training study. It consisted of a daily training programme containing simple movements to increase the flexibility of the chest, a breathing exercise and a relaxation session as well as symptom registration. Chest expansion was measured with a measuring tape and thoracic and abdominal movement with light sensors. Pain sensitivity was assessed using pressure algometry and a standardized capsaicin inhalation threshold provocation evaluated cough sensitivity. RESULTS: Twenty seven patients were left for analyses after 12 weeks and 26 patients after 24 weeks. Chest mobility and upper thoracic respiratory movements improved (p < 0.01), feeling of chest pressure and the capsaicin cough sensitivity decreased (p < 0.01). The patients also showed of significantly lowered pain pressure thresholds measured with algometry, compared with healthy controls (p < 0.001). CONCLUSION: Improvement of chest mobility after physiotherapeutic intervention indicates that these patients may have acquired a dysfunctional breathing pattern. The regular use of a training programme and structural breathing instructions can be used to improve chest mobility, chest symptoms and capsaicin cough sensitivity in patients with SHR and signs of dysfunctional breathing. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26847529 TI - Incomplete Conflict of Interest Disclosure. PMID- 26847528 TI - Bladder Cancer is Associated with Low Plasma 25-hydroxyvitamin D Concentrations in Tunisian Population. AB - Little evidence suggests an impact of vitamin D on bladder cancer risk in Caucasians. This study aimed to investigate association of plasma 25 hydroxyvitamin D (25-OHD) with urothelial bladder cancer (UBC) risk in Tunisians. A case-control study included 250 patients with UBC and 250 healthy controls. Plasma 25-OHD was assessed by a competitive chemiluminescence immunoassay. Vitamin D deficiency and insufficiency were defined as 25-OHD <30 nmol/L and 30 to 49.99 nmol/L, respectively. Logistic regression models adjusting for gender, age, smoking status, duration of smoking, occupational exposure, and season were applied. Vitamin D deficiency (50.4% vs. 34.8%; P < 0.001) and insufficiency (40.4% vs. 26.8%; P < 0.001) were more frequent in patients than controls. Multivariate analysis showed that UBC is associated with vitamin D deficiency [odd-ratio (95% confidence interval), 3.71 (1.76-7.80); P = 0.001] and vitamin D insufficiency [2.65 (1.40-5.01); P = 0.003]. Other predictors of UBC were female gender, tobacco use, smoking duration, and occupational exposure. Plasma 25-OHD concentrations are low in Tunisian patients with UBC. These findings support experimental and epidemiological evidence of protective role of vitamin D against UBC but could not ascertain causal relationship. Further prospective studies and clinical trials are warranted to check causality. PMID- 26847530 TI - miR-24 regulates CDKN1B/p27 expression in prostate cancer. AB - BACKGROUND: MicroRNAs (miRNAs) are small, non-coding RNA molecules with an important role in cancer. In prostate cancer, several miRNAs are expressed abnormally suggesting they may be useful markers for diagnosis, prognosis, and potential therapeutic intervention in this disease. However, the contribution of individual miRNAs to the development and progression of this disease remains poorly understood. This study investigated the role of miR-24, which has not been extensively studied in relation to prostate cancer. METHODS: We used PCR to investigate the expression of miR-24 in a panel of prostate cancer cell-lines and in a series of clinical prostate biopsy specimens. The biological significance of miR-24 expression in prostate cancer cells was assessed by a series of in vitro bioassays and the effect on proposed targets p27 (CDKN1B) and p16 (CDK2NA) was investigated. RESULTS: We showed that miR-24 expression was significantly lower in prostate cancer cell lines compared to a normal prostate epithelial cell line. Decreased expression of miR-24 was also more frequently observed in both needle core and prostatectomy tumor tissue relative to matched normal tissue. Low miR-24 expression correlated with high PSA serum levels and other markers of increased prostate cancer progression. Importantly, over-expression of miR-24 inhibited cell cycle, proliferation, migration, and clonogenic potential of prostate cancer cells, as well as inducing apoptosis. p27 and p16 were confirmed as targets of miR-24 in prostate cancer cells and a significant inverse correlation between miR 24 and p27 was revealed in clinical prostatectomy specimens. CONCLUSIONS: These findings provide evidence that miR-24 has a tumor suppressor role in prostate cancer and also targets p27 and p16 in prostate cancer cells. We propose that it may be a useful progression biomarker or focus of therapeutic intervention for this disease. PMID- 26847531 TI - The hidden sentinel node in breast cancer: Reevaluating the role of SPECT/CT and tracer reinjection. AB - INTRODUCTION: Lymphoscintigraphy with planar imaging is considered a helpful tool to depict lymph node drainage in patients with invasive breast cancer. Single Photon Emission Computed Tomography with integrated CT (SPECT/CT) is usually performed to detect sentinel nodes (SN)s in breast cancer patients showing non visualisation on lymphoscintigraphy. Incorporation of new SN indications (recurrent surgery, previous radiotherapy, or neo-adjuvant chemotherapy) has led to an increase of non-visualisation rates. The present study evaluates the contribution of SPECT/CT and tracer reinjection for SN-visualisation in breast cancer patients without drainage on lymphoscintigraphy. METHODS: Between 1st of July 2008 and 6th of November 2014 in total 1968 patients underwent a SN breast procedure, using intra-tumoural tracer administration. SPECT/CT was performed in 284 breast cancer patients with non-visualisation of SNs on lymphoscintigraphy. If SN non-visualisation persisted, a second radiotracer injection with repeated imaging was performed when logistics allowed this. Univariate analysis was applied to evaluate SPECT/CT visualisation rates in specific subgroups. RESULTS: The SPECT/CT visualisation rate was 23.2% (66/284). Univariate analysis revealed no significant subgroups influencing SPECT/CT visualisation. In patients receiving reinjection after persistent SPECT/CT non-visualisation the SN visualisation rate reached 62.1% (36/58). Intraoperatively, the SN-identification rate using a gamma probe and blue dye was 87.9% (175/199) and 32.9% (28/85) for, respectively, primary and recurrent surgery after non-visualisation on lymphoscintigraphy. CONCLUSION: In this evaluation including new breast cancer SN indications, SPECT/CT scored lower than reinjection to visualise SNs in patients with non-visualisation on lymphoscintigraphy. Consequently, our institutional protocol has been readjusted. PMID- 26847532 TI - Psychometric evaluation of the DMSS-4 in a cohort of elderly post-operative hip fracture patients with delirium. AB - BACKGROUND: Delirium is a common neuropsychiatric syndrome with considerable heterogeneity in clinical profile. Rapid reliable identification of clinical subtypes can allow for more targeted research efforts. METHODS: We explored the concordance in attribution of motor subtypes between the Delirium Motor Subtyping Scale 4 (DMSS-4) and the original Delirium Motor Subtyping Scale (DMSS) (assessed cross-sectionally) and subtypes defined longitudinally using the Delirium Symptom Interview (DSI). RESULTS: We included 113 elderly patients developing DSM-IV delirium after hip-surgery [mean age 86.9 +/- 6.6 years; range 65-102; 68.1% females; 25 (22.1%) had no previous history of cognitive impairment]. Concordance for the first measurement was high for both the DMSS-4 and original DMSS (k = 0.82), and overall for the DMSS-4 and DSI (k = 0.84). The DMSS-4 also demonstrated high internal consistency (McDonald's omega = 0.90). The DSI more often allocated an assessment to "no subtype" compared to the DMSS-4 and DMSS-11, which showed higher inclusion rates for motor subtypes. CONCLUSIONS: The DMSS-4 provides a rapid method of identifying motor-defined clinical subtypes of delirium and appears to be a reliable alternative to the more detailed and time consuming original DMSS and DSI methods of subtype attribution. The DMSS-4, so far translated into three languages, can be readily applied to further studies of causation, treatment and outcome in delirium. PMID- 26847533 TI - Overexpression of KiSS-1 reduces colorectal cancer cell invasion by downregulating MMP-9 via blocking PI3K/Akt/NF-kappaB signal pathway. AB - Metastasis of colorectal cancer (CRC) depends critically on MMP-9. KiSS-1 is a human malignant melanoma metastasis-suppressor gene. Thus, the interaction between MMP-9 and KiSS-1 has drawn considerable attention in recent years. In the present study, it was hypothesized that KiSS-1 gene could repress the metastatic potential of colorectal cancer cells by inhibiting the expression of MMP-9. Stable transfection of KiSS-1 specific siRNA and KiSS-1 expression vector in human CRC cell line HCT-116 was achieved by lentivirus infection. Moreover, the cell proliferation, invasiveness, and apoptosis were evaluated by CCK-8 method, transwell experiment, and fluorescence activated cell sorter, respectively. We also investigated the expression of MMP-9, PI3K, Akt, pAKt, and NF-kB subunit p65 using western blotting. KiSS-1 overexpression significantly decreased the cell proliferation and invasiveness of HCT-119 cells, while apoptosis was enhanced. The result of western blotting showed that synthesis of MMP-9, PI3K, p65, and phosphorylation of Akt were significantly blocked by overexpression of KiSS-1. Concatenated treatment of KiSS-1 overexpression vector with PI3K and Akt agonists attenuated the effect of KiSS-1 on the biological activity of CRC cells and also released the expression of MMP-9, PI3K, p65, and phosphorylation of Akt from the influence of overexpression of KiSS-1. Overexpression of KiSS-1 suppressed the invasiveness of CRC cells, and the gene exerted its function by reducing the expression of MMP-9 via blocking of tge PI3K/Akt/NF-kappaB pathway. PMID- 26847535 TI - [Reporting potential conflicts of interest]. PMID- 26847534 TI - Negative regulation of initial steps in skeletal myogenesis by mTOR and other kinases. AB - The transition from a committed progenitor cell to one that is actively differentiating represents a process that is fundamentally important in skeletal myogenesis. Although the expression and functional activation of myogenic regulatory transcription factors (MRFs) are well known to govern lineage commitment and differentiation, exactly how the first steps in differentiation are suppressed in a proliferating myoblast is much less clear. We used cultured mammalian myoblasts and an RNA interference library targeting 571 kinases to identify those that may repress muscle differentiation in proliferating myoblasts in the presence or absence of a sensitizing agent directed toward CDK4/6, a kinase previously established to impede muscle gene expression. We identified 55 kinases whose knockdown promoted myoblast differentiation, either independently or in conjunction with the sensitizer. A number of the hit kinases could be connected to known MRFs, directly or through one interaction node. Focusing on one hit, Mtor, we validated its role to impede differentiation in proliferating myoblasts and carried out mechanistic studies to show that it acts, in part, by a rapamycin-sensitive complex that involves Raptor. Our findings inform our understanding of kinases that can block the transition from lineage commitment to a differentiating state in myoblasts and offer a useful resource for others studying myogenic differentiation. PMID- 26847536 TI - [A comparison of two different doses of morphine added to spinal bupivacaine for inguinal hernia repair]. AB - BACKGROUND AND OBJECTIVES: The aim of this study was to compare the effects of two different doses of intrathecal morphine on postoperative analgesia, postoperative first mobilization and urination times and the severity of side effects. METHODS: After Institutional Ethical Committee approval, 48 ASA I-II patients were enrolled in this randomized double-blinded study. Spinal anesthesia was performed with 0.1mg (Group I, n=22) or 0.4mg (Group II, n=26) ITM in addition to 7.5mg heavy bupivacaine. The first analgesic requirement, first mobilization and voiding times, and postoperative side effects were recorded. Statistical analyses were performed using SPSS 15.0 and p<0.05 was considered as statistically significant. The numeric data were analyzed by the t-test and presented as mean+/-SD. Categorical data were analyzed with the chi-square test and expressed as number of patients and percentage. RESULTS: Demographic data were similar among groups. There were no differences related to postoperative pain, first analgesic requirements, and first mobilization and first voiding times. The only difference between two groups was the vomiting incidence. In Group II 23% (n=6) of the patients had vomiting during the first postoperative 24h compared to 0% in Group I (p=0.025). CONCLUSION: For inguinal hernia repairs, the dose of 0.1mg of ITM provides comparable postoperative analgesia with a dose of 0.4mg, with significantly lower vomiting incidence when combined with low dose heavy bupivacaine. PMID- 26847537 TI - [Perioperative cardiac arrest: an evolutionary analysis of the intra-operative cardiac arrest incidence in tertiary centers in Brazil]. AB - BACKGROUND: Great changes in medicine have taken place over the last 25 years worldwide. These changes in technologies, patient risks, patient profile, and laws regulating the medicine have impacted the incidence of cardiac arrest. It has been postulated that the incidence of intraoperative cardiac arrest has decreased over the years, especially in developed countries. The authors hypothesized that, as in the rest of the world, the incidence of intraoperative cardiac arrest is decreasing in Brazil, a developing country. OBJECTIVES: The aim of this study was to search the literature to evaluate the publications that relate the incidence of intraoperative cardiac arrest in Brazil and analyze the trend in the incidence of intraoperative cardiac arrest. CONTENTS: There were 4 articles that met our inclusion criteria, resulting in 204,072 patients undergoing regional or general anesthesia in two tertiary and academic hospitals, totalizing 627 cases of intraoperative cardiac arrest. The mean intraoperative cardiac arrest incidence for the 25 years period was 30.72:10,000 anesthesias. There was a decrease from 39:10,000 anesthesias to 13:10,000 anesthesias in the analyzed period, with the related lethality from 48.3% to 30.8%. Also, the main causes of anesthesia-related cause of mortality changed from machine malfunction and drug overdose to hypovolemia and respiratory causes. CONCLUSIONS: There was a clear reduction in the incidence of intraoperative cardiac arrest in the last 25 years in Brazil. This reduction is seen worldwide and might be a result of multiple factors, including new laws regulating the medicine in Brazil, incorporation of technologies, better human development level of the country, and better patient care. PMID- 26847538 TI - [Ultrasound guidance improves the success rate of axillary plexus block: a meta analysis]. AB - OBJECTIVE: To evaluate the value of real-time ultrasound (US) guidance for axillary brachial plexus block (AXB) through the success rate and the onset time. METHODS: The meta-analysis was carried out in the Anesthesiology Department of the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China. A literature search of Medline, Embase, Cochrane database from the years 2004 to 2014 was performed. The literature searches were carried out using medical subject headings and free-text word: "axilla", "axillary", "brachial plexus", "ultrasonography", "ultrasound", "ultrasonics". Two different reviewers carried out the search and evaluated studies independently. RESULTS: Seven randomized controlled trials, one cohort study and three retrospective studies were included. A total of 2042 patients were identified. 1157 patients underwent AXB using US guidance (US group) and the controlled group included 885 patients (246 patients using traditional approach (TRAD) and 639 patients using nerve stimulation (NS)). Our analysis showed that the success rate was higher in the US group compared to the controlled group (90.64% vs. 82.21%, p<0.00001). The average time to perform the block and the onset of sensory time were shorter in the US group than the controlled group. CONCLUSION: The present study demonstrated that the real-time ultrasound guidance for axillary brachial plexus block improves the success rate and reduce the mean time to onset of anesthesia and the time of block performance. PMID- 26847539 TI - [The association between thenar eminence and I-gelTM dimensions in paediatric patients]. AB - OBJECTIVES: A practical anatomic landmark may be helpful to perform the appropriate size of the airway devices easily in paediatric patients. The aim of this study was to investigate the association between thenar eminence and I-gel dimensions in children. METHODS: After Institutional Ethics Committee approval, two hundred and seventy ASA Class I-II patients between 0 and 12 years old, who were scheduled for elective procedures under general anaesthesia not requiring tracheal intubation, were recruited to the study. The size of the I-gel selected was based on the patient's body weight according to the manufacturer's recommendation. After successful insertion of the I-gel, thenar eminence dimensions were determined. Long-axis (Th-l) was measured from junction point of the thumb to wrist curl and short-axis (Th-w) constitutes the largest portion of the thenar eminence from lateral end of the thumb to the first hand line. The manufacturer's dimensions of the I-gel which was inserted into the patients were compared with the measurements obtained from thenar eminence. RESULTS: The mean (SD) values for (Ig-w) and (Ig-l) were 2.98cm (0.53) and 4.54cm (0.82), and the mean (SD) values for (Th-w) and (Th-l) were 2.99cm (0.60) and 3.88cm (0.93), respectively. There was a statistically significant correlation between Th-w and Ig-w (r=0.794, p<0.001), and between Th-l and Ig-l (r=0.820, p<0.001). CONCLUSION: The dimensions of thenar eminence were fitted to that of the weight based size of I-gel and this anatomic landmark may be a practical tool to assess appropriate size for paediatric patients. PMID- 26847540 TI - [Prophylactic use of pregabalin for prevention of succinylcholine-induced fasciculation and myalgia: a randomized, double-blinded, placebo-controlled study]. AB - BACKGROUND: Succinylcholine is commonly used to achieve profound neuromuscular blockade of rapid onset and short duration. OBJECTIVE: The present study compared the efficacy of pregabalin for prevention of succinylcholine-induced fasciculation and myalgia. DESIGN: Prospective, randomized, placebo controlled, double blinded study. MATERIALS AND METHODS: Patients of both genders undergoing elective spine surgery were randomly assigned to two groups. Patients in Group P (pregabalin group) received 150mg of pregabalin orally 1h prior to induction of anesthesia with sips of water and patients in Group C (control group) received placebo. Anesthesia was induced with fentanyl 1.5mcg/kg, propofol 1.5-2.0mg/kg followed by succinylcholine 1.5mg/kg. The intensity of fasciculations was assessed by an observer blinded to the group allotment of the patient on a 4 point scale. A blinded observer recorded postoperative myalgia grade after 24h of surgery. Patients were provided patient-controlled analgesia with fentanyl for postoperative pain relief. RESULTS: Demographic data of both groups were comparable (p>0.05). The incidence of muscle fasciculation's was not significant between two groups (p=0.707), while more patients in group C had moderate to severe fasciculation's compared to group P (p=0.028). The incidence and severity of myalgia were significantly lower in group P (p<0.05). CONCLUSION: Pregabalin 150mg prevents succinylcholine-induced fasciculations and myalgia and also decreases the fentanyl consumption in elective sine surgery. PMID- 26847541 TI - Mass cytometry moving forward in support of clinical research: advantages and considerations. PMID- 26847542 TI - A specific photoimmunotheranostics agent to detect and eliminate skin cancer cells expressing EGFR. AB - PURPOSE: The term "theranostics" represents a new paradigm in medicine especially for cancer treatment. This term was coined by Funkhouser in 2002 and defines a reagent that combines therapeutic and diagnostic properties. It is widely believed that theranostics agents will have considerable impact on healthcare before, during, and after disease by improving cancer prognosis and management simultaneously. Current theranostics approaches still rely on passive tumor targeting strategies, which have scattergun effects and tend to damage both neoplastic and non-neoplastic cells. METHODS: Here we describe a simple, controlled, and efficient method to generate homogeneous photoimmunotheranostics reagents. This method combines molecular optical imaging, photodynamic therapy, and immunotherapy using SNAP-tag technology. SNAP-tag is a derivative of the O(6) alkylguanine-DNA alkyltransferase (AGT) which has the ability to efficiently conjugate to O(6)-benzylguanine (BG) molecules under physiological conditions depending on its folding pattern. RESULTS: The theranostics agent was able to specifically recognize various epidermal growth factor receptor (EGFR)-expressing skin cancer cell lines using flow cytometry analysis and confocal microscopy and eliminate them at EC50's of 32-55 nM. CONCLUSIONS: These experiments provide a framework for using SNAP-tag technology to generate homogeneous photoimmunotheranostics reagents with unified pharmacokinetic and therapeutic profiles. Furthermore, the reagent generated in this work could be used to simultaneously monitor and suppress the growth of skin squamous carcinoma and melanoma cells expressing EGFR. PMID- 26847543 TI - Metaphyseal dysplasia associated with chronic facial nerve palsy. AB - INTRODUCTION: Metaphyseal dysplasia (Pyle disease) is a rare autosomal recessive disease with impressive and characteristic radiological findings but relatively mild clinical features. It is usually incidentally diagnosed, despite the impressive radiological findings of gross metaphyseal widening and thinning of cortical bone. CASE REPORT: Herein, we report an exceptionally unusual case of metaphyseal dysplasia in association with chronic facial nerve palsy. DISCUSSION: Chronic facial nerve palsy due to compression of the facial nerve in a patient with Pyle disease represents an unusual novelty. Furthermore, this case delineates the clinical spectrum and phenotype of such a rare clinical entity. To the best of our knowledge, this is the first time that such an association is being described. PMID- 26847544 TI - Nuclear magnetic resonance detection and spectroscopy of single proteins using quantum logic. AB - Nuclear magnetic resonance spectroscopy is a powerful tool for the structural analysis of organic compounds and biomolecules but typically requires macroscopic sample quantities. We use a sensor, which consists of two quantum bits corresponding to an electronic spin and an ancillary nuclear spin, to demonstrate room temperature magnetic resonance detection and spectroscopy of multiple nuclear species within individual ubiquitin proteins attached to the diamond surface. Using quantum logic to improve readout fidelity and a surface-treatment technique to extend the spin coherence time of shallow nitrogen-vacancy centers, we demonstrate magnetic field sensitivity sufficient to detect individual proton spins within 1 second of integration. This gain in sensitivity enables high confidence detection of individual proteins and allows us to observe spectral features that reveal information about their chemical composition. PMID- 26847545 TI - CLK2 inhibition ameliorates autistic features associated with SHANK3 deficiency. AB - SH3 and multiple ankyrin repeat domains 3 (SHANK3) haploinsufficiency is causative for the neurological features of Phelan-McDermid syndrome (PMDS), including a high risk of autism spectrum disorder (ASD). We used unbiased, quantitative proteomics to identify changes in the phosphoproteome of Shank3 deficient neurons. Down-regulation of protein kinase B (PKB/Akt)-mammalian target of rapamycin complex 1 (mTORC1) signaling resulted from enhanced phosphorylation and activation of serine/threonine protein phosphatase 2A (PP2A) regulatory subunit, B56beta, due to increased steady-state levels of its kinase, Cdc2-like kinase 2 (CLK2). Pharmacological and genetic activation of Akt or inhibition of CLK2 relieved synaptic deficits in Shank3-deficient and PMDS patient-derived neurons. CLK2 inhibition also restored normal sociability in a Shank3-deficient mouse model. Our study thereby provides a novel mechanistic and potentially therapeutic understanding of deregulated signaling downstream of Shank3 deficiency. PMID- 26847546 TI - Tuft cells, taste-chemosensory cells, orchestrate parasite type 2 immunity in the gut. AB - The intestinal epithelium forms an essential barrier between a host and its microbiota. Protozoa and helminths are members of the gut microbiota of mammals, including humans, yet the many ways that gut epithelial cells orchestrate responses to these eukaryotes remain unclear. Here we show that tuft cells, which are taste-chemosensory epithelial cells, accumulate during parasite colonization and infection. Disruption of chemosensory signaling through the loss of TRMP5 abrogates the expansion of tuft cells, goblet cells, eosinophils, and type 2 innate lymphoid cells during parasite colonization. Tuft cells are the primary source of the parasite-induced cytokine interleukin-25, which indirectly induces tuft cell expansion by promoting interleukin-13 production by innate lymphoid cells. Our results identify intestinal tuft cells as critical sentinels in the gut epithelium that promote type 2 immunity in response to intestinal parasites. PMID- 26847548 TI - Neonatal Jaundice with Splenomegaly: Not a Common Pick. AB - The most common conditions causing cholestatic jaundice in infants are biliary atresia, neonatal hepatitis, and Alagille syndrome. In these disorders, the clinical presentation includes jaundice, pale stools, dark urine and hepatomegaly. Splenomegaly is not an early feature since it is due to portal hypertension, a later event. The finding of cholestatic jaundice and a large spleen usually raises the suspicion of Niemann-Pick type C disease (NP-C), a lysosomal storage disorder. We present and discuss here a case of an infant with liver disease and splenomegaly that were not ascribed to NP-C, but to Gaucher disease type 2. Liver biopsy, enzymatic studies and whole exome sequencing allowed to make the diagnosis. Although rare, Gaucher disease can cause neonatal hepatitis. A prompt recognition is advocated. PMID- 26847550 TI - Satiety and the Self-Regulation of Food Take in Children: a Potential Role for Gene-Environment Interplay. AB - Child eating self-regulation refers to behaviors that enable children to start and stop eating in a manner consistent with maintaining energy balance. Perturbations in these behaviors, manifesting as poorer child eating self regulation, are associated with higher child weight status. Initial research into child eating self-regulation focused on the role of parent feeding styles and behaviors. However, we argue that child eating self-regulation is better understood as arising from a complex interplay between the child and their feeding environment, and highlight newer research into the heritable child characteristics, such as cognitive ability, that play an important role in this dynamic. Therefore, child eating self-regulation arises from gene-environment interactions. Identifying the genes and environmental influences contributing to these will help us tailor our parental feeding advice to the unique nature of the child. In this way, we will devise more effective advice for preventing childhood obesity. PMID- 26847547 TI - The role of immune cells in metabolism-related liver inflammation and development of non-alcoholic steatohepatitis (NASH). AB - The low grade inflammatory state present in obesity promotes the progression of Non-Alcoholic Fatty Liver Disease (NAFLD). In Non-Alcoholic Steatohepatitis (NASH), augmented hepatic steatosis is accompanied by aberrant intrahepatic inflammation and exacerbated hepatocellular injury. NASH is an important disorder and can lead to fibrosis, cirrhosis and even neoplasia. The pathology of NASH involves a complex network of mechanisms, including increased infiltration of different subsets of immune cells, such as monocytes, T-lymphocytes and neutrophils, to the liver, as well as activation and in situ expansion of liver resident cells such as Kupffer cells or stellate cells. In this review, we summarize recent advances regarding understanding the role of the various cells of the innate and adaptive immunity in NASH development and progression, and discuss possible future therapeutic options and tools to interfere with disease progression. PMID- 26847551 TI - Attitudes of Austrian veterinarians towards euthanasia in small animal practice: impacts of age and gender on views on euthanasia. AB - BACKGROUND: Euthanasia of pets has been described by veterinarians as "the best and the worst" of the profession. The most commonly mentioned ethical dilemmas veterinarians face in small animal practice are: limited treatment options due to financial constraints, euthanizing of healthy animals and owners wishing to continue treatment of terminally ill animals. The aim of the study was to gain insight into the attitudes of Austrian veterinarians towards euthanasia of small animals. This included assessing their agreement with euthanasia in exemplified case scenarios, potentially predicted by demographic variables (e.g. gender, age, working in small animal practice, employment, working in a team, numbers of performed euthanasia). Further describing the veterinarians' agreement with a number of different normative and descriptive statements, including coping strategies. A questionnaire with nine euthanasia scenarios, 26 normative and descriptive statements, and demographic data were sent to all members of the Austrian Chamber of Veterinary Surgeons (n = 2478). RESULTS: In total, 486 veterinarians answered sufficiently completely to enable analyses. Responses were first explored descriptively before being formally analysed using linear regression and additive Bayesian networks - a multivariate regression methodology - in order to identify joint relationships between the demographic variables, the statements and each of the nine euthanasia scenarios. Mutual dependencies between the demographic variables were found, i.e. female compared to male veterinarians worked mostly in small animal practice, and working mostly in small animal practice was linked to performing more euthanasia per month. CONCLUSIONS: Gender and age were found to be associated with views on euthanasia: female veterinarians and veterinarians having worked for less years were more likely to disagree with euthanasia in at least some of the convenience euthanasia scenarios. The number of veterinarians working together was found to be the variable with the highest number of links to other variables, demographic as well as ethical statements. This highlights the role of a team potentially providing support in stressful situations. The results are useful for a better understanding of coping strategies for veterinarians with moral stress due to euthanasia of small animals. PMID- 26847552 TI - Pattern of animal bites and post exposure prophylaxis in rabies: A five year study in a tertiary care unit in Sri Lanka. AB - BACKGROUND: Rabies is a global problem which occurs in more than 150 countries and territories including Sri Lanka, where human deaths from rabies are in decline whilst resources incurred for prevention of rabies are in sharp incline over the years. In this backdrop, we aim to audit the post-exposure treatment (PET) in rabies and the pattern of animal bites in a tertiary care hospital in Sri Lanka. METHODS: This study was carried out at Teaching Hospital Peradeniya (THP), in the Central Province of Sri Lanka from 2007-2012 where a registry of all PET has been maintained. The data from registries were extracted after obtaining permission from the hospital authority for analysis. RESULTS: There were 19 661 cases of animal exposure presented to the THP over the study period of 5 ears. Of them, the majority-17431(88.66 %) were definitive animal bites whilst scratches accounted for 2147(10.92 %) and 83(0.42 %) were miscellaneous exposures. According to the severity grading of injuries, 7 362(37 %) were major bites and 12 226(62 %) were minor bites. The domestic unvaccinated dogs and cats were responsible for 10,662 (54 %) and 3,982 (20 %) of exposures respectively. The total cost incurred for both anti-rabies vaccine and anti rabies serum during the study period is 24,795,888.00 Sri Lankan rupees (190,737.60US$). CONCLUSIONS: The pattern of animal bite shows high dominance of domestic dogs and cats exposures. The age of victims ranged from infancy to old-age with higher incidence among children. Even though PET is costly, continued surveillance and rabies control is still necessary along with public education and vaccination of domestic pets. PMID- 26847553 TI - Association between glaucoma eye drops and hyperemia. AB - PURPOSE: We used an image analysis software program to quantitatively investigate conjunctival injection in patients treated with eye drops for glaucoma. METHODS: We compared 169 patients (89 men and 80 women) with a diagnosis of glaucoma. Photographs of the conjunctiva were taken on the temporal side of each patient's right eye using a slit lamp. We determined the mean pixel frequencies of the conjunctival blood vessels from the photographs. RESULTS: The ocular hyperemia of the patients being treated with prostaglandins was more severe than that of the patients being treated with beta-blockers or no eye drops. In multiple comparisons of each of the eye drops, the control group had a significantly lower degree of hyperemia than did the patients being treated with each of the various prostaglandin analogs (latanoprost, travoprost, tafluprost, and bimatoprost). Among the patients receiving prostaglandin, the percentage of those with hyperemia was highest in the bimatoprost users, followed in order by the travoprost, latanoprost, and tafluprost users. However, no significant differences were found among the different prostaglandin analogs in terms of the percentage of patients with hyperemia. CONCLUSION: Our software program may be useful for evaluating the hyperemic effects of eye drops used for glaucoma. The particular type of prostaglandin analog seems to determine the level of conjunctival hyperemia during ocular hypotensive medical treatment. PMID- 26847555 TI - The emergence of psychiatric semiology during the Age of Revolution: evolving concepts of 'normal' and 'pathological'. AB - This article addresses some important questions in psychiatric semiology. The concept of a sign is crucial in psychiatry. How do signs emerge, and what gives them validity and legitimacy? What are the boundaries of 'normal' and 'pathological' behaviour and mental experiences? To address these issues, we analyse the characteristics and rules that govern semiological signs and clinical elements. We examine 'normality' from the perspective of Georges Canguilehm and compare the differences of 'normal' in physiology and psychiatry. We then examine the history and the philosophical, linguistic and medical-psychiatric origins of semiology during the eighteenth and nineteenth centuries (the Age of Revolution). The field of rhetoric and oratory has emphasized the importance of passions, emotions and language as applied to signs of madness. Another perspective on semiology, provided by Michel Foucault, lays stress on the concept of 'instinct' and the axis of voluntary-involuntary behaviour. Finally, we analyse how statistics and eugenics have played an important role in our current conceptualization of the norm and therefore the scientific discourse behind the established clinical signs. PMID- 26847554 TI - Mental health outcomes in times of economic recession: a systematic literature review. AB - BACKGROUND: Countries in recession experience high unemployment rates and a decline in living conditions, which, it has been suggested, negatively influences their populations' health. The present review examines the recent evidence of the possible association between economic recessions and mental health outcomes. METHODS: Literature review of records identified through Medline, PsycINFO, SciELO, and EBSCO Host. Only original research papers, published between 2004 and 2014, peer-reviewed, non-qualitative research, and reporting on associations between economic factors and proxies of mental health were considered. RESULTS: One-hundred-one papers met the inclusion criteria. The evidence was consistent that economic recessions and mediators such as unemployment, income decline, and unmanageable debts are significantly associated with poor mental wellbeing, increased rates of common mental disorders, substance-related disorders, and suicidal behaviours. CONCLUSION: On the basis of a thorough analysis of the selected investigations, we conclude that periods of economic recession are possibly associated with a higher prevalence of mental health problems, including common mental disorders, substance disorders, and ultimately suicidal behaviour. Most of the research is based on cross-sectional studies, which seriously limits causality inferences. Conclusions are summarised, taking into account international policy recommendations concerning the cost-effective measures that can possibly reduce the occurrence of negative mental health outcomes in populations during periods of economic recession. PMID- 26847557 TI - Erratum to: Fatty acid composition in fetal, neonatal, and cultured cardiomyocytes in rats. PMID- 26847558 TI - What drove the evolution of endothermy? PMID- 26847556 TI - Relationship between dietary patterns and risk factors for cardiovascular disease in patients with type 2 diabetes mellitus: a cross-sectional study. AB - BACKGROUND: While some dietary patterns are associated with the incidence of type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), the relationship between dietary pattern and risk factors for CVD in patients with T2DM remains to be clarified. The aim of this study was to identify dietary patterns and investigate the relationship between dietary patterns and potential risk factors for CVD in patients with T2DM. METHODS: The study participants comprised 726 Japanese T2DM outpatients free of history of CVD. Life styles were analyzed using self-reported questionnaires. The relationship between dietary patterns, identified by factor analysis, and potential risk factors for CVD was investigated by linear and logistic regression analyses. RESULTS: Six dietary patterns were identified by factor analysis. Especially, three dietary patterns were associated with risk factors for CVD. The "Seaweeds, Vegetables, Soy products and Mushrooms" pattern, characterized by high consumption of seaweeds, soy products and mushrooms, was associated with lower use of diabetes medication and healthier lifestyles. The "Noodle and Soup" pattern, characterized by high consumption of noodle and soup was associated with higher body mass index, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and triglyceride levels. The "Fruit, Dairy products and Sweets" pattern was associated with lower gamma-glutamyl transpeptidase levels, blood pressure, albuminuria and brachial-ankle pulse wave velocity. CONCLUSIONS: The findings suggested that dietary patterns correlated with risk factors for CVD in T2DM patients. PMID- 26847559 TI - European shags optimize their flight behavior according to wind conditions. AB - Aerodynamics results in two characteristic speeds of flying birds: the minimum power speed and the maximum range speed. The minimum power speed requires the lowest rate of energy expenditure per unit time to stay airborne and the maximum range speed maximizes air distance traveled per unit of energy consumed. Therefore, if birds aim to minimize the cost of transport under a range of wind conditions, they are predicted to fly at the maximum range speed. Furthermore, take-off is predicted to be strongly affected by wind speed and direction. To investigate the effect of wind conditions on take-off and cruising flight behavior, we equipped 14 European shags Phalacrocorax aristotelis with a back mounted GPS logger to measure position and hence ground speed, and a neck-mounted accelerometer to record wing beat frequency and strength. Local wind conditions were recorded during the deployment period. Shags always took off into the wind regardless of their intended destination and take-off duration was correlated negatively with wind speed. We combined ground speed and direction during the cruising phase with wind speed and direction to estimate air speed and direction. Whilst ground speed was highly variable, air speed was comparatively stable, although it increased significantly during strong head winds, because of stronger wing beats. The increased air speeds in head winds suggest that birds fly at the maximum range speed, not at the minimum power speed. Our study demonstrates that European shags actively adjust their flight behavior to utilize wind power to minimize the costs of take-off and cruising flight. PMID- 26847560 TI - Diet-induced phenotypic plasticity in European eel (Anguilla anguilla). AB - Two phenotypes are present within the European eel population: broad-heads and narrow-heads. The expression of these phenotypes has been linked to several factors, such as diet and differential growth. The exact factors causing this dimorphism, however, are still unknown. In this study, we performed a feeding experiment on glass eels from the moment they start to feed. Eels were either fed a hard diet, which required biting and spinning behavior, or a soft diet, which required suction feeding. We found that the hard feeders develop a broader head and a larger adductor mandibulae region than eels that were fed a soft diet, implying that the hard feeders are capable of larger bite forces. Next to this, soft feeders develop a sharper and narrower head, which could reduce hydrodynamic drag, allowing more rapid strikes towards their prey. Both phenotypes were found in a control group, which were given a combination of both diets. These phenotypes were, however, not as extreme as the hard or the soft feeding group, indicating that some specimens are more likely to consume hard prey and others soft prey, but that they do not selectively eat one of both diets. In conclusion, we found that diet is a major factor influencing head shape in European eel and this ability to specialize in feeding on hard or soft prey could decrease intra specific competition in European eel populations. PMID- 26847561 TI - Comparative analysis of fertility signals and sex-specific cuticular chemical profiles of Odontomachus trap-jaw ants. AB - The lipid mixture that coats the insect cuticle contains a number of chemical signals. Mate choice in solitary insects is mediated by sexually dimorphic cuticular chemistry, whereas in eusocial insects, these profiles provide information through which colony members are identified and the fertility status of individuals is assessed. Profiles of queens and workers have been described for a number of eusocial species, but there have been few comparisons of fertility signals among closely related species. Additionally, sexual dimorphism in cuticular lipid profiles has only been reported in two species of ants. This study describes the cuticular chemical profiles of queens, workers and males of three species of Odontomachus trap-jaw ants: O. ruginodis, O. relictus and O. haematodus. These are compared with fertility signals and sexually dimorphic profiles already described from O. brunneus. We report that fertility signals are not conserved within this genus: chemical compounds that distinguish queens from workers vary in number and type among the species. Furthermore, the compounds that were most abundant in cuticular extracts of O. ruginodis queens relative to workers were novel 2,5-dialkyltetrahydrofurans. Bioassays of extracts of O. ruginodis queens indicate that the dialkyltetrahydrofuran and hydrocarbon fractions of the profile are likely to work synergistically in eliciting behavioral responses from workers. In contrast, cuticular lipids that distinguish males from females are more conserved across species, with isomeric and relative abundance variations comprising the main differences among species. Our results provide new insights into how these contact chemical signals may have arisen and evolved within eusocial insects. PMID- 26847563 TI - Metallothioneins in Normal and Cancer Cells. AB - Metallothioneins (MTs) are low molecular weight proteins, which are present in almost all types of organisms. In mammals, four main MT isoforms designated from MT-1 to MT-4 were identified. Their biological role, according to their characteristic structure, was shown to be mostly associated with cellular metabolism of metal ions, especially zinc. Moreover, the available evidence suggests broad regulatory properties of MTs in the control of cell senescence and various pathological processes including neurodegeneration, cardiovascular pathology, metabolic disorders, and various malignancies. This extensive review provides general in formation on the structure of MT family members and the cellular functions of MT-1, MT-2, and MT-4 isoforms as well as insights into divergent biological roles of MT-3. Due to the involvement of MT molecules in various processes related to carcinogenesis, an organ-specific presentation of current data concerning their potential impact on the progression of various tumors is given. The regulatory role of MT family members in the function of the immune system is also discussed in depth. PMID- 26847568 TI - Polyacrylamide Gel-Entrapped Maltase: An Excellent Design of Using Maltase in Continuous Industrial Processes. AB - Bacterial maltase catalyzes the hydrolysis of maltose and is known as one of the most significant hydrolases. It has several applications in different industrial processes but widely used in food fermentation technology and alcohol production. In the current study, entrapment technique was comprehensively examined using polyacrylamide gel as a matrix support to improve the stability and catalytic efficiency of maltase for continuous use. Maximum entrapment yield of maltase was achieved at 10 % polyacrylamide concentration with 3.0-mm bead size. Optimized conditions indicated an increase in the reaction temperature from 45 to 55 degrees C after maltase entrapment while no change was observed in the reaction time and pH. An increase in the K m value of entrapped maltase was attained whereas V max value decreased from 8411.0 to 6813.0 U ml(-1) min(-1) with reference to its free counterpart. Entrapped maltase showed remarkable thermal stability and retained 16 % activity at 70 degrees C even after 120.0 min. Entrapped maltase also exhibited excellent recycling efficiency up to eight consecutive reaction cycles. With respect to economic feasibility, entrapped maltase indicates its high potential to be used in various biotechnological applications. PMID- 26847562 TI - Incidence of, phenotypes of and survival from small bowel cancer in Denmark, 1994 2010: a population-based study. AB - BACKGROUND: Small bowel cancer (SBC) is a rare and highly heterogeneous disease in respect to both anatomical distribution and histological morphology. We aimed to conduct a Danish nationwide population-based cohort study of the incidence of, phenotypes of, stage of, synchronous/metachronous cancer occurrence of and survival from SBC during 1994-2010. METHODS: The study population included all individuals aged 16 years or older living in Denmark during 1994-2010 (n = 7,070,142). Patients with SBC were identified through the Danish Cancer Registry. Incidence rates were calculated overall and according to the anatomical origin and morphological subtype. Patients were followed up from the date of cancer diagnosis to the date of emigration, death or the end of the study (31 December 2010). RESULTS: SBC was diagnosed in 1088 patients during 1994-2010. The total annual incidence of SBC was 1.10 per 100,000 [95 % confidence interval (CI) 1.04 to 1.17 per 100,000], with an annual percentage change of 1.9 % (95 % CI 0.6-3.1 %, p = 0.003) during the observation period. This increase was mainly explained by an increase in the occurrence of duodenal adenocarcinomas, with an annual percentage change of 7.5 % (95 % CI 4.9-10.2 %, p < 0.001). Further, 29 % of all SBC patients had metastatic cancer at the time of diagnosis and 32 % had one or more synchronous/metachronous cancers. All morphological subtypes were associated with poor 5-year prognoses, in particular duodenal adenocarcinomas, with a 5-year survival rate of only 16 % (95 % CI 12-22 %). CONCLUSIONS: The incidence of SBC has increased in recent decades, mainly because of a large increase in the incidence of duodenal adenocarcinomas, which are also associated with the poorest prognosis. PMID- 26847569 TI - Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation. AB - BACKGROUND: In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold-storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold-preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation. METHODS: The preservation solution Celsior saturated with pure argon (Argon-Celsior) or xenon (Xenon-Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air-Celsior). The left kidney was removed, and Air-Celsior (n = 8 pigs), Argon-Celsior (n = 8) or Xenon Celsior (n = 6) was used at 4 degrees C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air-Celsior was used. Heterotopic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days. RESULTS: The use of Argon-Celsior vs. Air-Celsior: (1) improved function recovery as monitored via creatinine clearance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2-3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day-21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the "reduced ascorbic acid/thiobarbituric acid reactive substances" ratio and Hsp27 expression; (6) limited the inflammatory response as shown by expression of TNF alpha, IL1-beta and IL6 as observed after the natural death/euthanasia. Conversely, Xenon-Celsior was detrimental, no animal surviving by day-8 in a context where functional recovery, renal tissue properties and the antioxidant and inflammation responses were significantly altered. Thus, the positive effects of argon were not attributable to the noble gases as a group. CONCLUSIONS: The saturation of Celsior with argon improved early functional recovery, graft quality and survival. Manipulating the gas composition of a preservation medium constitutes therefore a promising approach to improve preservation. PMID- 26847570 TI - [Subjective job strain and job satisfaction among neurologists in German hospitals]. AB - BACKGROUND: The number of sick leaves due to job strain is increasing. OBJECTIVE: This study's scope is to examine working conditions of neurologists in hospitals in regard to job strain and job satisfaction. METHODS: This study is part of the iCEPT-Study. The iCEPT-Study was conducted as a web based survey among physicians (n = 7090) in German hospitals. The focus was on working conditions regarding job strain. Job strain was measured by a questionnaire consisting of items and scales from the short version of the Effort-Reward-Imbalance (ERI) questionnaire and the short questionnaire for working analysis (KFZA). By calculation ratios of distinct scales according to validated stress models a conclusion could be drawn as to whether or not job strain was present. RESULTS: The total number of n = 354 neurologists were analyzed. The response rate was at 18.2 %. Job strain was encountered by 52.0 % (95 %-KI: 46.7|57.2) of all neurologists and no significant gender difference was present. However, resident neurologists were significantly more often exposed to job strain than attending neurologists (OR = 2.9; 95 %-KI: 1.6-4.7; p < 0.001). Regarding job satisfaction, 59.6 % (95 %-KI: 54.5-64.7) of all respondents stated to be satisfied with their job. Significantly more men were satisfied than women (OR = 1.5; 95 %-KI: 1.0-2.4; p < 0.05). Putting the focus on different occupational positions revealed that significantly more attendings were satisfied with their job than residents (OR = 2.9; 95 %-KI: 1.7 4.8; p < 0.001). CONCLUSION: The results of this study showed high prevalence of job strain among neurologists in German hospitals. Keeping the negative implications of mental and physical health in mind, the working conditions of neurologists must be improved. As shown in this study, a possible way to do so is to increase job control in order to decrease a major stressor at work. PMID- 26847571 TI - Effect of late sodium current inhibition on MRI measured diastolic dysfunction in aortic stenosis: a pilot study. AB - BACKGROUND: Ranolazine is a new anti-anginal drug that acts via late sodium current inhibition, and has been shown to improve diastolic dysfunction in isolated myocytes. Diastolic dysfuntion is common in patients with aortic stenosis (AS), and precedes symptom development and systolic dysfunction. The purpose of this study was to assess the effects of ranolazine on peak early diastolic strain rate (PEDSR) and exercise capacity in patients with AS. METHODS: Patients with asymptomatic moderate to severe AS and diastolic dysfunction underwent trans-thoracic echocardiography, exercise testing and cardiac magnetic resonance (CMR) imaging at baseline, 6 weeks after commencing ranolazine and at 10 weeks (4 weeks after discontinuation). Diastolic function was assessed using PEDSR measured on tagged CMR images. RESULTS: Fifteen patients (peak pressure gradient 48.8 +/- 12.4 mmHg, mean pressure gradient 27.1 +/- 7.5 mmHg, aortic valve area 1.26 +/- 0.31 cm(2)) completed the week-6 visit and 13 completed the final visit. Global PEDSR did not significantly increase from baseline (0.79 +/- 0.15) to week-6 (0.86 +/- 0.18, p = 0.198). There was a borderline significant increase in total exercise duration from 10.47 +/- 3.68 min to 11.60 +/- 3.25 min (p = 0.06). CONCLUSION: This small pilot study did not show a significant improvement in diastolic function with the use of ranolazine in asymptomatic patients with moderate-severe AS. Further studies with a larger population may be indicated. EduraCT number 2011-000111-26. PMID- 26847572 TI - Ultrasound-guided "short" midline catheters for difficult venous access in the emergency department: a retrospective analysis. AB - BACKGROUND: Acutely ill patients admitted to the emergency department (ED) constantly require at least one fast and reliable peripheral intravenous (PIV) access. In many conditions (morbid obesity, underweight state, chronic diseases, intravenous drug abuse, adverse local conditions, etc.), PIV placement may be challenging. Ultrasound guidance is a useful tool for obtaining a peripheral intravenous access in the emergency department, particularly when superficial veins are difficult to identify by palpation and direct visualization, though standard peripheral intravenous cannulas are not ideal for this technique of insertion and may have limited duration. Long polyurethane catheters inserted with ultrasound guidance and direct Seldinger technique appear to have several advantages over short cannulas in terms of success of insertion and of duration. METHODS: A retrospective analysis was conducted on all the ultrasound-guided peripheral venous accesses obtained by insertion of long polyurethane catheters in patients admitted to the emergency department of our university hospital during 1 year. The main indication to the procedure was the urgent need of a peripheral venous access in patients with superficial veins difficult to palpate and/or visualize. All relevant data concerning the insertion and the maintenance of these peripheral lines were collected from the chart. RESULTS: Seventy-six patients were included in this review. The success rate of insertion was 100 %, with an average of 1.57 punctures per each successful cannulation. The mean time needed for the complete procedure was 9.5 min. In 73 % of patients, the catheter was used for more than 1 week; a minority of catheters were removed prematurely for end of use. No major infective or thrombotic complication was reported. CONCLUSIONS: In our experience, 8- to 10-cm-long polyurethane catheters may offer a fast and reliable peripheral venous access in the emergency department, if placed by ultrasound guidance and with the Seldinger technique. Further studies with prospective, randomized, and controlled design are warranted to confirm our results. PMID- 26847573 TI - ACE-Inhibition Benefit on Lung Function in Heart Failure is Modulated by ACE Insertion/Deletion Polymorphism. AB - PURPOSE: The benefit of angiotensin converting enzyme (ACE) inhibition in chronic heart failure (HF) is partially due to its effects on pulmonary function and particularly on lung diffusion, the latter being counteracted by acetylsalicylic acid (ASA). Tissue ACE activity is largely determined by an insertion/deletion (I/D) polymorphism resulting in three possible genotypes (DD, ID and II). It is not clear if ACE inhibitor therapy could exert different effects in these genotypes. The aim of the study was to understand whether I/D polymorphism interferes with ACE inhibitor's protection of the lungs in HF during acute fluid overload. METHODS: 100 HF patients (left ventricular ejection fraction <=40 %) in stable clinical conditions, treated with enalapril but without ASA performed pulmonary function tests including lung diffusion (DLco) and its subcomponents, membrane diffusion (Dm) and capillary volume (Vcap), and a cardiopulmonary exercise test before and immediately after rapid infusion of 500 cc saline. RESULTS: ACE I/D genotype prevalence was: DD = 28, ID =55 and II = 17 cases. No significant differences in major pulmonary function and exercise parameters were observed before saline infusion among ACE genotypes. After fluid challenge, DD patients presented a higher DLco and Dm reduction than ID and II (DLco -2.3 +/- 1.3 vs. -0.8 +/- 1.9 and -0.6 +/- 1 mL/mmHg/min, p < 0.0001 and p < 0.01; Dm -7 +/- 5 vs. -3.2 +/- 7.4 and -1.3 +/- 5 mL/mmHg/min, p < 0.05, respectively) and a higher increase in VE/VCO2 slope than II (1.8 +/- 1.9 vs. -0.8 +/- 2.3, p = 0.01). CONCLUSIONS: ACE DD genotype is associated with higher vulnerability of the alveolar-capillary membrane to acute fluid overload in HF patients treated with ACE inhibitors. PMID- 26847574 TI - Non-uniform sampling of NMR relaxation data. AB - The use of non-uniform sampling of NMR spectra may give significant reductions in the data acquisition time. For quantitative experiments such as the measurement of spin relaxation rates, non-uniform sampling is however not widely used as inaccuracies in peak intensities may lead to errors in the extracted dynamic parameters. By systematic reducing the coverage of the Nyquist grid of (15)N Carr Purcell-Meiboom-Gill (CPMG) relaxation dispersion datasets for four different proteins and performing a full data analysis of the resulting non-uniform sampled datasets, we have compared the performance of the multi-dimensional decomposition and iterative re-weighted least-squares algorithms in reconstructing spectra with accurate peak intensities. As long as a single fully sampled spectrum is included in a series of otherwise non-uniform sampled two-dimensional spectra, multi dimensional decomposition reconstructs the non-uniform sampled spectra with high accuracy. For two of the four analyzed datasets, a coverage of only 20% results in essentially the same results as the fully sampled data. As exemplified by other data, such a low coverage is in general not enough to produce reliable results. We find that a coverage level not compromising the final results can be estimated by recording a single full two-dimensional spectrum and reducing the spectrum quality in silico. PMID- 26847575 TI - Effect of prior drought and pathogen stress on Arabidopsis transcriptome changes to caterpillar herbivory. AB - In nature, plants are exposed to biotic and abiotic stresses that often occur simultaneously. Therefore, plant responses to combinations of stresses are most representative of how plants respond to stresses. We used RNAseq to assess temporal changes in the transcriptome of Arabidopsis thaliana to herbivory by Pieris rapae caterpillars, either alone or in combination with prior exposure to drought or infection with the necrotrophic fungus Botrytis cinerea. Pre-exposure to drought stress or Botrytis infection resulted in a significantly different timing of the caterpillar-induced transcriptional changes. Additionally, the combination of drought and P. rapae induced an extensive downregulation of A. thaliana genes involved in defence against pathogens. Despite a more substantial growth reduction observed for plants exposed to drought plus P. rapae feeding compared with P. rapae feeding alone, this did not affect weight increase of this specialist caterpillar. Plants respond to combined stresses with phenotypic and transcriptional changes that differ from the single stress situation. The effect of a previous exposure to drought or B. cinerea infection on transcriptional changes to caterpillars is largely overridden by the stress imposed by caterpillars, indicating that plants shift their response to the most recent stress applied. PMID- 26847576 TI - Identification of genes regulated by histone acetylation during root development in Populus trichocarpa. AB - BACKGROUND: Histone deacetylases (HDACs) are key enzymes catalyzing the removal of acetyl groups from histones. HDACs act in concert with histone acetyltransferases (HATs) to regulate histone acetylation status, which modifies chromatin structure, affecting gene transcription and thus regulating multiple biological processes such as plant growth and development. Over a decade, certain HDACs in herbaceous plants have been deeply studied. However, functions of HDACs in woody plants are not well understood. RESULTS: Histone deacetylase specific inhibitor trichostatin A (TSA) was used to investigate the role of HDACs in organogenesis of roots and root development in Populus trochocarpa. The adventitious roots were regenerated and grown on medium supplemented with 0, 1, and 2.5 MUM TSA. TSA treatment delayed root regeneration and inhibited primary root growth. To examine the genes modified by TSA in the regenerated roots, tag based digital gene expression (DGE) analysis was performed using Illumina HiSeqTM 2000. Approximately 4.5 million total clean tags were mapped per library. The distinct clean tags for the three libraries corresponding to 0, 1 and 2.5 MUM TSA treatment were 166167, 143103 and 153507, from which 38.45%, 31.84% and 38.88% were mapped unambiguously to the unigene database, respectively. Most of the tags were expressed at similar levels, showing a < 5-fold difference after 1 MUM and 2.5 MUM TSA treatments and the maximum fold-change of the tag copy number was around 20. The expression levels of many genes in roots were significantly altered by TSA. A total of 36 genes were up-regulated and 1368 genes were down regulated after 1 MUM TSA treatment, while 166 genes were up-regulated and 397 genes were down-regulated after 2.5 MUM TSA treatment. Gene ontology (GO) and pathway analyses indicated that the differentially expressed genes were related to many kinds of molecular functions and biological processes. The genes encoding key enzymes catalyzing gibberellin biosynthesis were significantly down-regulated in the roots exposed to 2.5 MUM TSA and their expression changes were validated by using real-time PCR. CONCLUSIONS: HDACs were required for de novo organogenesis and normal growth of populus roots. DGE data provides the gene profiles in roots probably regulated by histone acetylation during root growth and development, which will lead to a better understanding of the mechanism controlling root development. PMID- 26847577 TI - Frequency of chromosome 17 polysomy in relation to CEP17 copy number in a large breast cancer cohort. AB - Eligibility to anti-HER2 therapy for breast tumors strictly depends on demonstrating HER2 overexpression (by immunohistochemistry) or HER2 gene amplification by in situ hybridization (ISH), usually defined by the ratio of HER2 gene to chromosome 17 centromere (CEP17) copies. However, the CEP17 copy number increase (CNI) has been proven responsible for misleading HER2 FISH results and recent small cohort studies suggest that chromosome 17 polysomy is actually very rare. Here we investigated by FISH the frequency of true chromosome 17 polysomy in a consecutive cohort of 5,477 invasive breast cancer patients. We evaluated and selected the LSI 17p11.2 probe for chromosome 17 enumeration on a training cohort of 67 breast cancer samples (CEP17 >= 2.5). LSI 17p11.2 was used in the 297/5,477 patients from the validation cohort displaying CEP17 CNI (CEP17 >= 3.0). Using HER2/17p11.2 scoring criteria, 37.3%/1.5% patients initially classified as equivocal/non-amplified were reclassified as amplified. For a more accurate assessment of chromosome 17 and ploidy in the samples, we tested six markers located on chromosome 17 and centromeric regions of chromosome 8 (CEP8) and 11 (CEP11) in 67 patients with CEP17 and LSI 17p11.2 CNI. True polysomy (hyperdiploidy) according to these markers was found in 0.48% of cases (24/5,020). CEP8 and CEP11 CNI (>=3.0) was more frequent in the hyperdiploid than CEP17 non-polysomic group (55.6% vs. 6.1% and 25% vs. 2.3%, respectively). Our results suggest that chromosome 17 polysomy is a rare event found in <1% breast cancer cases and that polysomy of other chromosomes frequently occurs with chromosome 17 polysomy. PMID- 26847579 TI - WHO analgesic ladder gone astray: wider implications. PMID- 26847580 TI - Is the effect of topical intranasal steroids on obstructive adenoids transient or long-lasting? Case series and systematic review of literature. AB - OBJECTIVES: To study and review the short- and long-term effects of intranasal steroids on obstructive adenoids. METHODS: In this prospective cohort study, 19 children previously treated with mometasone furoate for 3 months were contacted at 3, 6 and 12 months after cessation of treatment. Main outcome measures included: change in severity of nasal obstruction, allergic rhinitis and obstructive symptoms. A systematic review of literature was also performed. RESULTS: By one year, 25 per cent of patients required adenoidectomy; the remaining children had no significant change in clinical score (p = 0.464), obstruction severity (p = 0.191) or allergic symptoms (p = 0.284). Fourteen pertinent studies were identified; all but one study showed improvement in the patients' symptoms and/or degree of obstruction. Two studies with follow up reaching 25 months showed positive effects. CONCLUSION: The short-term positive effect of some intranasal steroids on obstructive adenoids seems to persist in a significant number of patients after the cessation of treatment. PMID- 26847581 TI - Proton conductivity and phase transitions in 1,2,3-triazole. AB - 1,2,3-Triazole (TR) is a good proton conductor which is tidely related to formation of a hydrogen bond network along the N-HN trajectory and its self dissociation into diH-1,2,3-triazolium and 1,2,3-triazolate. To gain a deeper understanding, the proton conductivity of TR is measured by impedance spectroscopy (IS) across its melting temperature and an additionally discovered solid-solid phase transition. The orthorhombic high temperature phase and the monoclinic low temperature modification are investigated by polarized optical microscopy, DSC- and WAXS measurements. Furthermore, the diffusion coefficients of TR are determined from IS data and measured by (1)H PFG NMR spectroscopy in the melt which allows for separate evaluation of contributions of proton hopping across the hydrogen bond network and the vehicle mechanism to the proton conductivity where the vehicles are defined as charged species generated by TR self-dissociation. Finally, the degree of dissociation of TR is calculated and the influence of the self-dissociation of TR on the proton conductivity is discussed in the context of the dielectric constant. PMID- 26847578 TI - Androgen-related sperm storage in oviduct of Chinese Soft-Shelled Turtle in vivo during annual cycle. AB - Long-term sperm storage in the female genital tract is essential for the appropriate timing of reproductive events in animals with asynchronous copulation and ovulation. However, the mechanism underlying the prolonged storage of spermatozoa is largely unexplored in turtles. In the present study, the role of androgen in sperm storage was investigated in the oviduct of the Chinese soft shelled turtle, Pelodiscus sinensis. Morphological analysis revealed that spermatozoa were observed in the vagina, uterus and isthmus of the oviduct throughout the hibernation season. The increase of circulating testosterone and dihydrotestosterone levels were consistent with the arrangement of spermatozoa that had their head embedded among the cilia of the oviduct mucosal epithelium. Immunohistochemical analysis revealed that androgen receptor was distributed throughout the cytoplasm of gland cells and among the cilia of ciliated cells. Furthermore, marked variations in protein and mRNA levels of androgen receptor were validated through Western blot and qPCR analyses. The localization and the variation of androgen receptor demonstrated the crucial roles of androgens in sperm storage in the oviduct of P. sinensis. These results provide fundamental insights into the interaction of androgen and sperm storage and facilitate the elucidation of the mechanism of sperm storage in turtles. PMID- 26847582 TI - Insulin autoimmune syndrome during the administration of clopidogrel. PMID- 26847583 TI - The Role of the Interface in Thin Film and Droplet Accelerated Reactions Studied by Competitive Substituent Effects. AB - Based on a study of competitive substituent effects in a Claisen-Schmidt reaction, interfacial effects have been shown to play an important role in accelerated reactions that occur in thin films and droplets. A role for the interface in an accelerated C-C bond-formation reaction between 6hydroxy-1 indanone and aromatic aldehydes is indicated by cooperative interactions between p-methylbenzaldehyde and p-nitrobenzaldehyde. Additional acceleration over that occurring in bulk reactions is seen for p-methylbenzaldehyde, but only in the presence of p-nitrobenzaldehyde. A decrease in the degree of acceleration is detected when the reaction is forced electrostatically to occur inside the thin film, and the interface is shown to participate in the accelerated reactions. This experimental evidence for interfacial thin film and droplet acceleration supports a recent model and builds on earlier work which locates molecules within evaporating droplets in electrosprays. PMID- 26847584 TI - Label-free and pH-sensitive colorimetric materials for the sensing of urea. AB - This communication demonstrates a facile method for naked-eye detection of urea based on the structure color change of pH-sensitive photonic crystals. The insertion of urease provides excellent selectivity over other molecules. The detection of urea in different concentration ranges could be realized by changing the molar ratio between the functional monomer and cross-linker. PMID- 26847585 TI - Older Age, Higher Body Mass Index and Inflammation Increase the Risk for New Onset Diabetes and Impaired Glucose Tolerance in Patients on Peritoneal Dialysis. AB - ? OBJECTIVES: To identify predictors of new-onset diabetes and impaired glucose tolerance (IGT) events in patients undergoing peritoneal dialysis (PD) based on baseline and time-dependent covariates, respectively. ? METHODS: In this prospective, single center-based cohort, all non-diabetic incident PD patients between August 2003 and August 2011 were included. All demographic and laboratory data were recorded at baseline. Repeated measurements for laboratory, dialysis prescription, and nutrition parameters were recorded at regular intervals. Multivariable Cox regression models built from baseline and time-dependent variables respectively were used to calculate the hazard ratio (HR) of potential predictors for new-onset diabetes and IGT (NODI). ? RESULTS: Of the 612 PD patients, 25 (4.1%) and 7 (1.1%) patients were identified with NODI, respectively, during a mean follow-up period of 32.4 (12.9 - 60.8) months. Using multivariable Cox regression analysis, age and body mass index (BMI) at baseline were significantly associated with NODI after adjustment for potential confounders. During follow-up, time-dependent BMI and serum high-sensitive C reactive protein (HS-CRP) independently predicted the risk for NODI. Patients with NODI had significantly elevated plasma glucose concentrations and BMI from the start of PD therapy, with serum HS-CRP maintained at high levels. Dietary/dialysate energy intake and other laboratory parameters were not correlated with NODI risk either as baseline or time-dependent variables. ? CONCLUSIONS: Traditional and uremic-related risk factors, such as older age, higher BMI, and inflammation, contribute to new-onset diabetes and impaired glucose tolerance in PD patients. PMID- 26847586 TI - Is Adapted APD Theoretically More Efficient than Conventional APD? AB - ? BACKGROUND: A modified version of automated peritoneal dialysis (APD) using not only variable dwell times but also variable fill volumes has been tested against conventional APD (cAPD) with fixed dwell volumes in a randomized controlled clinical study. The results have indicated that the modified schedule for APD, denoted adapted APD (aAPD), can lead to improved small solute clearances, and, above all, a markedly increased sodium removal (NaR). To theoretically test these results, we have modeled aAPD vs cAPD in computer simulations using the 3-pore model (TPM). ? METHODS: The TPM, modified by including a transient, initial inflation of small solute mass transfer area coefficients (PS values), was employed. For simulations of osmotic ultrafiltration (UF), the TPM uses a constantly inflated value for PS for glucose and also a reduced value for PS for Na+, setting the peritoneal lymphatic reabsorption term at 0.3 mL/min. The simulations were performed by assuming that increases in intraperitoneal hydrostatic pressure (IPP) are transmitted to the capillary level (via vein compression) and therefore do not significantly affect the Starling balance. Furthermore, the effective peritoneal surface area (A) was set to be variable as a function of intraperitoneal volume (IPV). ? RESULTS: The simulations demonstrated a minor improvement of small solute clearances (~0.7 - 1.6%) and a very small improvement of UF and NaR in aAPD compared to cAPD. ? CONCLUSIONS: Due mainly to the increased fill volumes in 3 out of 5 dwells in aAPD, this modality caused minor increases in small solute clearances and marginal effects on UF and NaR. The computer simulations point to a need for accurate sodium determinations in aAPD, considering all the methodological problems and pitfalls relevant to determining dialysate Na+ concentrations and peritoneal sodium mass balance. PMID- 26847587 TI - YL4073 is a potent autophagy-stimulating antitumor agent in an in vivo model of Lewis lung carcinoma. AB - Cancer cells activate autophagy in response to anticancer therapies. Autophagy induction is a promising therapeutic approach to treat cancer. In a previous study, YL4073 inhibited the growth of liver cancer and induced liver cancer cell apoptosis. Here, we demonstrated the anticancer activity and specific mechanisms of YL4073 in Lewis lung carcinoma LL/2 cells. Our results show that YL4073 induced autophagy was followed by apoptotic cell death. The anticancer and autophagy stimulating efficacy was confirmed by several factors, including the appearance of autophagic vacuoles, formation of acidic vesicular organelles, recruitment of microtubule-associated protein 1 light chain 3 II (LC3-II) to the autophagosomes, conversion and cleavage of LC3-I to LC3-II, upregulation of Beclin 1 expression, and formation of the Atg12-Atg5 conjugate in LL/2 cells after YL4073 treatment for 24 or 48 h. Furthermore, P53 activation and p-histone H3 phosphorylation occurred after cell exposure to YL4073 for 48 h, suggesting that cell apoptosis had occurred. Pharmacological inhibition of autophagy using 3 methyladenine increased cell apoptosis. Molecular level studies revealed that YL4073 inhibited survival signalling by blocking the activation of Akt and mTOR phosphorylation and reduced the expression of p-mTOR downstream targets for phosphorylation, including p70S6K, p-TSC, p-MAPK, and p-AMPK. This suggests that the Akt/mTOR/p70S6K and TSC/MAPK/AMPK pathways are involved in the effects of YL4073 treatment in LL/2 cells. In addition, YL4073 significantly inhibited LL/2 tumor growth and induced apoptosis in vivo. These data suggest that YL4073 has a significant anticancer effect, with a pathway-specific mechanism of autophagy both in vitro and in vivo. PMID- 26847588 TI - Failure of Colorectal Surgical Site Infection Predictive Models Applied to an Independent Dataset: Do They Add Value or Just Confusion? AB - BACKGROUND: Colorectal surgical site infections (C-SSIs) are a major source of postoperative morbidity. Institutional C-SSI rates are modeled and scrutinized, and there is increasing movement in the direction of public reporting. External validation of C-SSI risk prediction models is lacking. Factors governing C-SSI occurrence are complicated and multifactorial. We hypothesized that existing C SSI prediction models have limited ability to accurately predict C-SSI in independent data. STUDY DESIGN: Colorectal resections identified from our institutional ACS-NSQIP dataset (2006 to 2014) were reviewed. The primary outcome was any C-SSI according to the ACS-NSQIP definition. Emergency cases were excluded. Published C-SSI risk scores: the National Nosocomial Infection Surveillance (NNIS), Contamination, Obesity, Laparotomy, and American Society of Anesthesiologists (ASA) class (COLA), Preventie Ziekenhuisinfecties door Surveillance (PREZIES), and NSQIP-based models were compared with receiver operating characteristic (ROC) analysis to evaluate discriminatory quality. RESULTS: There were 2,376 cases included, with an overall C-SSI rate of 9% (213 cases). None of the models produced reliable and high quality C-SSI predictions. For any C-SSI, the NNIS c-index was 0.57 vs 0.61 for COLA, 0.58 for PREZIES, and 0.62 for NSQIP: all well below the minimum "reasonably" predictive c-index of 0.7. Predictions for superficial, deep, and organ space SSI were similarly poor. CONCLUSIONS: Published C-SSI risk prediction models do not accurately predict C SSI in our independent institutional dataset. Application of externally developed prediction models to any individual practice must be validated or modified to account for institution and case-mix specific factors. This questions the validity of using externally or nationally developed models for "expected" outcomes and interhospital comparisons. PMID- 26847589 TI - Intubated Trauma Patients Do Not Require Full Trauma Team Activation when Effectively Triaged. AB - BACKGROUND: Full trauma team activation in evaluating injured patients is based on triage criteria and associated with significant costs and resources that should be focused on patients who truly need them. Overtriage leads to inefficient care, particularly when resources are finite, and it diverts care from other vital areas. Although shock and gunshot wounds to the abdomen are accepted indicators for full trauma activation, intubation as the sole criterion is controversial. We evaluated our experience to assess if intubation alone merited the highest level of trauma activation. STUDY DESIGN: All trauma patients from 2012 to 2013 were assessed for level of activation, injury characteristics, presence of intubation, and outcomes. RESULTS: Of 5,881 patients, 646 (11%) were level 1 (full) and 2,823 (48%) were level 2 (partial) activations. Level 1 patients were younger (40 +/- 17 vs 45 +/- 20 years), had more penetrating injuries (42% vs 9%), and had higher mortality (26% vs 8%)(p < 0.001). Intubated level 2 patients (n = 513), compared with intubated level 1 patients (n = 320), had higher systolic blood pressure (133 +/- 44 vs 90 +/- 58 mmHg), lower Injury Severity Score (21 +/- 13 vs 25 +/- 16), more falls (25% vs 3%), fewer penetrating injuries (11% vs 23%), and lower mortality (31% vs 48%)(p < 0.01). Fewer intubated level patients went directly to the operating room from the emergency department (ED)(16% vs 33%), and most who did had a craniotomy (63% vs 13%). Only 3% of intubated level 2 patients underwent laparotomy compared with 20% of intubated level 1 patients (p < 0.001). The ED lengths of stay before obtaining a head CT (47 +/- 26 vs 48 +/- 31 minutes) and craniotomy (109 +/- 61 vs 102 +/- 46 minutes) were similar. Deaths in intubated level 2 patients were primarily from fatal brain injuries. CONCLUSIONS: When appropriately triaged, selected intubated trauma patients do not require full trauma activation to receive timely, efficient care. PMID- 26847591 TI - Beneficial effects of JAK inhibitor therapy in Systemic Mastocytosis. PMID- 26847590 TI - Heterogeneity in Trauma Registry Data Quality: Implications for Regional and National Performance Improvement in Trauma. AB - BACKGROUND: Led by the American College of Surgeons Trauma Quality Improvement Program, performance improvement efforts have expanded to regional and national levels. The American College of Surgeons Trauma Quality Improvement Program recommends 5 audit filters to identify records with erroneous data, and the Georgia Committee on Trauma instituted standardized audit filter analysis in all Level I and II trauma centers in the state. STUDY DESIGN: Audit filter reports were performed from July 2013 to September 2014. Records were reviewed to determine whether there was erroneous data abstraction. Percent yield was defined as number of errors divided by number of charts captured. RESULTS: Twelve centers submitted complete datasets. During 15 months, 21,115 patient records were subjected to analysis. Audit filter captured 2,901 (14%) records and review yielded 549 (2.5%) records with erroneous data. Audit filter 1 had the highest number of records identified and audit filter 3 had the highest percent yield. Individual center error rates ranged from 0.4% to 5.2%. When comparing quarters 1 and 2 with quarters 4 and 5, there were 7 of 12 centers with substantial decreases in error rates. The most common missed complications were pneumonia, urinary tract infection, and acute renal failure. The most common missed comorbidities were hypertension, diabetes, and substance abuse. CONCLUSIONS: In Georgia, the prevalence of erroneous data in trauma registries varies among centers, leading to heterogeneity in data quality, and suggests that targeted educational opportunities exist at the institutional level. Standardized audit filter assessment improved data quality in the majority of participating centers. PMID- 26847592 TI - Histone deacetylase 5 promotes Wilms' tumor cell proliferation through the upregulation of c-Met. AB - The histone deacetylase (HDAC) family is comprised of enzymes, which are involved in modulating the majority of critical cellular processes, including transcriptional regulation, apoptosis, proliferation and cell cycle progression. However, the biological function of HDAC5 in Wilms' tumor remains to be fully elucidated. The present study aimed to investigate the expression and function of HDAC5 in Wilm's tumor. It was demonstrated that the mRNA and protein levels of HDAC5 were upregulated in human Wilms' tumor tissues. Overexpression of HDAC5 in G401 cells was observed to significantly promote cellular proliferation, as demonstrated by the results of an MTT assay and bromodeoxyuridine incorporation assay. By contrast, HDAC5 knockdown using small interfering RNA suppressed the proliferation of the G401 cells. At the molecular level, the present study demonstrated that HDAC5 promoted the expression of c-Met, which has been previously identified as an oncogene. In addition, downregulation of c-Met inhibited the proliferative effects of HDAC5 in human Wilms' tumor cells. Taken together, these results suggested that HDAC5 promotes cellular proliferation through the upregulation of c-Met, and may provide a novel therapeutic target for the treatment of patients with Wilms' tumor. PMID- 26847593 TI - Silver Nanoclusters with Specific Ion Recognition Modulated by Ligand Passivation toward Fluorimetric and Colorimetric Copper Analysis and Biological Imaging. AB - Silver nanoclusters were synthesized and passivated by glutathione (GSH) ligand, with high aqueous stability and powerful red fluorescence and UV-vis yellow colour. Importantly, the specific recognition of the AgNCs was modulated from Hg(2+) ions to Cu(2+) ions upon the GSH passivation, of which the unique GSH Cu(2+) chelating reaction could conduct the fluorescence quenching of AgNCs. Strong UV-vis absorbance of GSH-passivated AgNCs could also be realized depending on the Cu(2+) levels. Moreover, the Cu(2+)-induced loss of fluorescence and UV vis absorbance of GSH-passivated AgNCs could be well restored by using stronger Cu(2+) chelating agent. A simultaneous and reversible fluorimetric and colorimetric sensing method was thereby developed for probing Cu(2+) ions in blood with high sensitivity and selectivity. Subsequently, the fluorescence trackable imaging for live tissues and cells was demonstrated towards the analysis Cu(2+) ions using GSH-passivated AgNCs as the fluorescent probes. This study indicates that the use of functional ligands like GSH could not only modulate the specific ion recognition of AgNCs, but also endow them the high aqueous stability and powerful red fluorescence towards the wide applications for ion sensing and biological imaging in the complicated media like blood. PMID- 26847596 TI - MicroRNA-26b is upregulated in a double transgenic mouse model of Alzheimer's disease and promotes the expression of amyloid-beta by targeting insulin-like growth factor 1. AB - Alzheimer's disease (AD) is the most common form of dementia among the aging population. It is pathologically characterized by synaptic impairment, accumulation of neurofibrillary tangles and amyloid-beta (Abeta) deposition. MicroRNA-26b (miR-26b) has been observed to be upregulated in the human temporal cortex in AD, however, the function of miR-26b has not been verified. Reverse transcription-quantitative polymerase chain reaction was conducted to investigate the expression levels of miR-26b in a double transgenic mouse model of AD. Following transfection of miR-26b or an miR-26b inhibitor, western blot analysis, enzyme-linked immunosorbent assay and luciferase assays were performed. The present study demonstrated that the expression levels of miR-26b were upregulated in a double transgenic mouse model of AD. It was also demonstrated that upregulation of miR-26b in N2a/APP cells downregulated the insulin-like growth factor 1 (IGF-1) protein expression level and promoted Abeta production, whereas inhibition of miR-26b in N2a/APP cells upregulated the IGF-1 protein level and suppressed Abeta production. Furthermore, miR-26b target sites in IGF-1 were confirmed using a luciferase assay in HEK293 cells. The present study may be useful in the development of effective therapeutic strategies against AD. PMID- 26847597 TI - Description and Evaluation of a Home-Based, Parent-Administered Program for Teaching Enhanced Natural Gestures to Individuals With Angelman Syndrome. AB - PURPOSE: This article describes and presents outcomes of a home-based, self administered version of the Enhanced Natural Gestures (ENG) program for individuals with Angelman syndrome. METHOD: Parents of 18 individuals (11 boys and 7 girls) with Angelman syndrome, in consultation with their speech-language pathologists, participated in a quasi-experimental "B" design in which they self administered an instructional program to teach their children to use enhanced natural gestures at home and/or in the community. Parents integrated 2 teaching methods, Mand-Model with time delay and Molding-Shaping, into their everyday interactions with their children. Parents reported outcomes of the program through goal attainment scaling and completion of the ENG Acceptability Rating Form. RESULTS: Children's overall achievements acquiring ENGs generally met or exceeded program (and parent) expectations. Most parents reported little difficulty self-administering the ENG program with their children and regarded the program positively across multiple dimensions. CONCLUSIONS: ENGs may, in conjunction with other forms of augmentative and alternative communication, represent a viable method of communication for many individuals with Angelman syndrome. Further research is warranted to explore the feasibility of ENGs with other populations of individuals with severe disabilities and complex communication challenges. PMID- 26847594 TI - Silver nanoparticles disrupt germline stem cell maintenance in the Drosophila testis. AB - Silver nanoparticles (AgNPs), one of the most popular nanomaterials, are commonly used in consumer products and biomedical devices, despite their potential toxicity. Recently, AgNP exposure was reported to be associated with male reproductive toxicity in mammalian models. However, there is still a limited understanding of the effects of AgNPs on spermatogenesis. The fruit fly Drosophila testis is an excellent in vivo model to elucidate the mechanisms underlying AgNP-induced defects in spermatogenesis, as germ lineages can be easily identified and imaged. In this study, we evaluated AgNP-mediated toxicity on spermatogenesis by feeding Drosophila with AgNPs at various concentrations. We first observed a dose-dependent uptake of AgNPs in vivo. Concomitantly, AgNP exposure caused a significant decrease in the viability and delay in the development of Drosophila in a dose-dependent manner. Furthermore, AgNP-treated male flies showed a reduction in fecundity, and the resulting testes contained a decreased number of germline stem cells (GSCs) compared to controls. Interestingly, testes exposed to AgNPs exhibited a dramatic increase in reactive oxygen species levels and showed precocious GSC differentiation. Taken together, our study suggests that AgNP exposure may increase ROS levels in the Drosophila testis, leading to a reduction of GSC number by promoting premature GSC differentiation. PMID- 26847595 TI - Higher augmentation index is associated with tension-type headache and migraine in middle-aged/older humans with obesity. AB - OBJECTIVE: Obesity is a major risk factor for chronic daily headaches, including migraine and tension-type headache (TTH). Although migraine is associated with increased risk of cardiovascular diseases (CVD), a relation between TTH and CVD risk has not been established. It was hypothesized that higher carotid-femoral pulse wave velocity (CFPWV) and augmentation index (AI), measures of aortic stiffness and pressure wave reflection, respectively, and biomarkers of CVD risk, would be higher among adults with obesity and migraine or TTH compared with those with no headache. METHODS: Adults with obesity (n = 93; body mass index >=30 kg/m(2) ) who were between 40 and 75 years old with at least one additional CVD risk factor were enrolled. Subjects had CFPWV and AI assessed and a complete neurological exam for diagnosis of headache in the past 12 months. RESULTS: Adults with obesity and TTH (P = 0.018), but not migraine (P = 0.29), had significantly higher AI compared with those with no headache. When both CFPWV and AI were considered in a logistic regression model with migraine or TTH, only AI was associated with TTH (P = 0.008) and migraine (P = 0.032) but could not distinguish between the two headache phenotypes. CONCLUSIONS: Increased aortic AI but not stiffness is associated with TTH and migraine among middle-aged/older adults with obesity and high CVD risk. PMID- 26847598 TI - The effect of periodontal therapy on intra-oral halitosis: a case series. AB - AIM: The aim of this study was to evaluate the effects of non-surgical periodontal therapy on intra-oral halitosis 3 months after therapy. MATERIAL AND METHODS: Sixty-eight adults with intra-oral halitosis were included in a case series. Intra-oral halitosis was evaluated at baseline, and at 3 months after treatment using the organoleptic scores (OLS), Halimeter(r) , and a gas chromatograph. RESULTS: Significant reductions for OLS (p < 0.01), total sum of volatile sulphur compounds (T-VSC) (p < 0.01) and methyl mercaptan (MM) (p < 0.05) values were found after treatment. Hydrogen sulphide (H2 S) levels were not significantly reduced. The numbers of probing pockets 4 mm, 5 mm and 6 mm were significantly reduced as a result of therapy (p < 0.001). Bleeding on probing (BOP) and plaque indices were also significantly reduced (p < 0.001). For the 34 individuals with successful periodontal treatment (BOP<20% and a >=50% reduction of total pocket depth) reductions in OLS (p < 0.01) and T-VSC scores (p < 0.01) were found. Eleven individuals were considered effectively treated for intra-oral halitosis presenting with a T-VSC value <160 ppb, a H2 S value <112 ppb and a MM value <26 ppb. CONCLUSION: Non-surgical periodontal therapy resulted in reduction of OLS, MM and T-VSC values 3 months after therapy. Few individuals were considered as effectively treated for intra-oral halitosis. PMID- 26847599 TI - Assessment of Household Disposal of Pharmaceuticals in Lebanon: Management Options to Protect Water Quality and Public Health. AB - Pharmaceuticals comprise an extensive group of compounds whose release into the environment has potential adverse impacts on human health and aquatic ecosystems. In many developing countries the extent of the problem and the occurrence of pharmaceuticals in water bodies are generally unknown. While thousands of tons of pharmaceutical substances are used annually, little information is known about their final fate after their intended use. This paper focuses on better understanding the management of human-use pharmaceutical wastes generated at the residential level within the Administrative Beirut Area. A survey encompassing 300 households was conducted. Results revealed that the majority of respondents were found to dispose of their unwanted medications, mainly through the domestic solid waste stream. Willingness to participate in a future collection program was found to be a function of age, medical expenditure, and the respondents' views towards awareness and the importance of establishing a collection system for pharmaceutical wastes. Respondents who stated a willingness to participate in a collection program and/or those who believed in the need for awareness programs on the dangers of improper medical waste disposal tended to favor more collection programs managed by the government as compared to a program run by pharmacies or to the act of re-gifting medication to people in need. Ultimately, collaboration and coordination between concerned stakeholders are essential for developing a successful national collection plan. PMID- 26847600 TI - Methylglyoxal and methylglyoxal-modified collagen as inducers of cellular injury in gingival connective tissue cells. AB - BACKGROUND AND OBJECTIVES: Methylglyoxal is a toxic product derived from glucose metabolism that plays a role in inflammation, diabetes and aging. In addition, the periodontal pathogen Tannerella forsythensis may also generate this compound. However, the effects of methylglyoxal on gingival cells are still poorly understood. In the present study, we have explored whether methylglyoxal or methylglyoxal-treated collagen may modulate cell viability, death and proliferation in gingival connective tissue cells. In addition, we have searched for inflammatory mediators secreted by cells upon exposure to these conditions. MATERIAL AND METHODS: Primary cultures of human gingival fibroblasts were stimulated with soluble methylglyoxal or cultured over a collagen matrix glycated by this agent. Cell viability was evaluated through the MTS assay. Cell death was assessed through DAPI nuclear staining, annexin V and propidium iodide assays. Cell proliferation was evaluated through double immunofluorescence for DAPI and Ki67. Protein levels of matrix metalloproteinases and cytokines were assessed through antibody arrays, enzyme-linked immunosorbent assay, real-time reverse transcription polymerase chain reaction and immunofluorescence. Statistical analysis was performed using the Kruskall-Wallis and Mann-Whitney tests. RESULTS: Soluble methylglyoxal, but not culture of gingival fibroblasts over a methylglyoxal-modified collagen matrix, induced a reduction on cell viability. Moreover, soluble methylglyoxal induced apoptotic cell death as indicated by DAPI nuclear staining, annexin V and propidium iodide assays. Neither soluble methylglyoxal, nor methylglyoxal-modified collagen modified cell proliferation. Using an antibody array, enzyme-linked immunosorbent assay and immunofluorescence assays, we determined that both, soluble methylglyoxal and methylglyoxal-modified collagen stimulated an increase in tissue inhibitor of metalloproteinase (TIMP)-1 protein levels. CONCLUSIONS: Soluble methylglyoxal is a highly cytotoxic compound that induces cell death through apoptosis in gingival fibroblasts. TIMP-1 is induced in these cells upon direct exposure to methylglyoxal or after culture of gingival fibroblasts over methylglyoxal-treated collagen. As TIMP-1 has been implicated in cell survival and matrix remodeling, we propose that increased TIMP 1 protein levels may be part of a protective response of gingival connective tissue cells upon exposure to methylglyoxal or after the interaction with the collagen matrix that has been modified by this agent. PMID- 26847601 TI - Triptolide reduces proliferation and enhances apoptosis of human non-small cell lung cancer cells through PTEN by targeting miR-21. AB - Triptolide is used in traditional Chinese medicine. It has the advantages of a unique mechanism of action, a wide antitumor spectrum, multiple targets, multi channel effects and low toxicity. The current study was conducted to evaluate whether the potential anticancer effects of triptolide reduces proliferation and enhances apoptosis of human non-small cell lung cancer (NSCLC) cells, and to assess the underlying anticancer mechanisms. In PC-9 cells, treatment with triptolide reduced cell proliferation and increased cell apoptosis and caspase-3 and 9 activity. Triptolide treatment reduced miR-21 expression and enhanced phosphatase and tensin homolog (PTEN) protein expression levels in the PC-9 cells. Furthermore, the upregulation of miR-21 expression levels suppressed the effect of triptolide on cell viability and PTEN protein expression levels in PC-9 cells. To the best of our knowledge, the present study is the first to demonstrate that triptolide reduced the proliferation and enhanced the apoptosis of human NSCLC cells through PTEN by targeting miR-21. PMID- 26847602 TI - Iron-catalysed cross-coupling of organolithium compounds with organic halides. AB - In past decades, catalytic cross-coupling reactions between organic halides and organometallic reagents to construct carbon-carbon bond have achieved a tremendous progress. However, organolithium reagents have rarely been used in cross-coupling reactions, due mainly to their high reactivity. Another limitation of this transformation using organolithium reagents is how to control reactivity with excellent selectivity. Although palladium catalysis has been applied in this field recently, the development of an approach to replace catalytic systems of noble metals with nonprecious metals is currently in high demand. Herein, we report an efficient synthetic protocol involving iron-catalysed cross-coupling reactions employing organolithium compounds as key coupling partners to unite aryl, alkyl and benzyl fragments and also disclose an efficient iron-catalysed release-capture ethylene coupling with isopropyllithium. PMID- 26847603 TI - Model of human cardiovascular system with a loop of autonomic regulation of the mean arterial pressure. AB - A model of human cardiovascular system is proposed which describes the main heart rhythm, the regulation of heart function and blood vessels by the autonomic nervous system, baroreflex, and the formation of arterial blood pressure. The model takes into account the impact of respiration on these processes. It is shown that taking into account nonlinearity and introducing the autonomous loop of mean arterial blood pressure in the form of self-oscillating time-delay system allow to obtain the model signals whose statistical and spectral characteristics are qualitatively and quantitatively similar to those for experimental signals. The proposed model demonstrates the phenomenon of synchronization of mean arterial pressure regulatory system by the signal of respiration with the basic period close to 10 seconds, which is observed in the physiological experiments. PMID- 26847604 TI - Use of Chemical Pesticides in Ethiopia: A Cross-Sectional Comparative Study on Knowledge, Attitude and Practice of Farmers and Farm Workers in Three Farming Systems. AB - Chemical pesticides, regardless of their inherent hazard, are used intensively in the fast changing agricultural sector of Ethiopia. We conducted a cross-sectional pesticide Knowledge, Attitude and Practice (KAP) survey among 601 farmers and farm workers (applicators and re-entry workers) in three farming systems [large scale closed greenhouses (LSGH), large-scale open farms (LSOF), and small-scale irrigated farms (SSIF)]. Main observations were that 85% of workers did not attain any pesticide-related training, 81% were not aware of modern alternatives for chemical pesticides, 10% used a full set of personal protective equipment, and 62% did not usually bath or shower after work. Among applicators pesticide training attendance was highest in LSGH (35%) and was lowest in SSIF (4%). None of the female re-entry farm workers had received pesticide-related training. Personal protective equipment use was twice as high among pesticide applicators as among re-entry workers (13 versus 7%), while none of the small-scale farm workers used personal protection equipment. Stockpiling and burial of empty pesticide containers and discarding empty pesticide containers in farming fields were reported in both LSOF and by 75% of the farm workers in SSIF. Considerable increment in chemical pesticide usage intensity, illegitimate usages of DDT and Endosulfan on food crops and direct import of pesticides without the formal Ethiopian registration process were also indicated. These results point out a general lack of training and knowledge regarding the safe use of pesticides in all farming systems but especially among small-scale farmers. This in combination with the increase in chemical pesticide usage in the past decade likely results in occupational and environmental health risks. Improved KAP that account for institutional difference among various farming systems and enforcement of regulatory measures including the available occupational and environmental proclamations in Ethiopia are urgently needed. PMID- 26847605 TI - Clinical prognostic value of metastasis-associated lung adenocarcinoma transcript 1 in various human cancers: an updated meta-analysis. AB - BACKGROUND: Many studies have investigated the prognostic value of metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in human cancers. However, these studies were often limited by small sample sizes. Therefore, we performed this updated meta-analysis to summarize the potential value of MALAT1 as a biomarker for early treatment and to predict survival in various human malignant neoplasms, through the inclusion of the latest literature and improved methodology. METHODS: Twelve eligible articles were systematically obtained from PubMed, Medline, Embase, Web of Science, China National Knowledge Infrastructure and the Cochrane Library, from inception up to June 30, 2015. Survival was assessed using pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: By combining the results of 12 studies, we found elevated MALAT1 expression was associated with poor survival in most cancers, with a pooled HR of 1.90 (95% CI, 1.56-2.30) for overall survival (OS) and 3.06 (95% CI, 2.06-4.56) for recurrence-free survival/disease-free survival. Subgroup analyses according to ethnicity, tumor type, assay method, sample size, HR-calculation method and analysis type did not affect the predictive role of MALAT1 for OS in various cancer types. Further, by combining results from studies that used multivariate analyses, we found elevated MALAT1 was an independent prognostic factor for OS (HR = 1.98; 95% CI, 1.58-2.48). CONCLUSIONS: MALAT1 could serve as a potential prognostic biomarker in various cancers and may be a potential therapeutic target for the treatment and early detection of recurrence. PMID- 26847606 TI - Molecular characterization and expression profiles of nicotinic acetylcholine receptors in the rice striped stem borer, Chilo suppressalis (Lepidoptera: Crambidae). AB - Nicotinic acetylcholine receptors (nAChRs) are members of the cys-loop ligand gated ion channel (cysLGIC) superfamily, mediating fast synaptic cholinergic transmission in the central nervous system in insects. Insect nAChRs are the molecular targets of economically important insecticides, such as neonicotinoids and spinosad. Identification and characterization of the nAChR gene family in the rice striped stem borer, Chilo suppressalis, could provide beneficial information about this important receptor gene family and contribute to the investigation of the molecular modes of insecticide action and resistance for current and future chemical control strategies. We searched our C. suppressalis transcriptome database using Bombyx mori nAChR sequences in local BLAST searches and obtained the putative nAChR subunit complementary DNAs (cDNAs) via reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends methods. Similar to B. mori, C. suppressalis possesses 12 nAChR subunits, including nine alpha-type and three beta-type subunits. Quantitative RT-PCR analysis revealed the expression profiles of the nAChR subunits in various tissues, including the brain, subesophageal ganglion, thoracic ganglion, abdominal ganglion, hemocytes, fat body, foregut, midgut, hindgut and Malpighian tubules. Developmental expression analyses showed clear differential expression of nAChR subunits throughout the C. suppressalis life cycle. The identification of nAChR subunits in this study will provide a foundation for investigating the diverse roles played by nAChRs in C. suppressalis and for exploring specific target sites for chemicals that control agricultural pests while sparing beneficial species. PMID- 26847608 TI - Frontal Fibrosing Alopecia Severity Index (FFASI): a validated scoring system for assessing frontal fibrosing alopecia. PMID- 26847609 TI - Is Empathic Accuracy Enough to Facilitate Responsive Behavior in Dyadic Interaction? Distinguishing Ability From Motivation. AB - Growing evidence suggests that interpersonal responsiveness-feeling understood, validated, and cared for by other people-plays a key role in shaping the quality of one's social interactions and relationships. But what enables people to be interpersonally responsive to others? In the current study, we argued that responsiveness requires not only accurate understanding but also compassionate motivation. Specifically, we hypothesized that understanding another person's thoughts and feelings (empathic accuracy) would foster responsive behavior only when paired with benevolent motivation (empathic concern). To test this idea, we asked couples (N = 91) to discuss a personal or relationship stressor; we then assessed empathic accuracy, empathic concern, and responsive behavior. As predicted, when listeners' empathic concern was high, empathic accuracy facilitated responsiveness; but when empathic concern was low, empathic accuracy was unhelpful (and possibly harmful) for responsiveness. These findings provide the first evidence that cognitive and affective forms of empathy work together to facilitate responsive behavior. PMID- 26847607 TI - Role of the Retinoblastoma protein, Rb, during adult neurogenesis in the olfactory bulb. AB - Adult neural stem cells (aNSCs) are relatively quiescent populations that give rise to distinct neuronal subtypes throughout life, yet, at a very low rate and restricted differentiation potential. Thus, identifying the molecular mechanisms that control their cellular expansion is critical for regeneration after brain injury. Loss of the Retinoblastoma protein, Rb, leads to several defects in cell cycle as well as neuronal differentiation and migration during brain development. Here, we investigated the role of Rb during adult neurogenesis in the olfactory bulb (OB) by inducing its temporal deletion in aNSCs and progenitors. Loss of Rb was associated with increased proliferation of adult progenitors in the subventricular zone (SVZ) and the rostral migratory stream (RMS) but did not alter self-renewal of aNSCs or neuroblasts subsequent migration and terminal differentiation. Hence, one month after their birth, Rb-null neuroblasts were able to differentiate into distinct subtypes of GABAergic OB interneurons but were gradually lost after 3 months. Similarly, Rb controlled aNSCs/progenitors proliferation in vitro without affecting their differentiation capacity. This enhanced SVZ/OB neurogenesis associated with loss of Rb was only transient and negatively affected by increased apoptosis indicating a critical requirement for Rb in the long-term survival of adult-born OB interneurons. PMID- 26847610 TI - Lignans from Schisandra chinensis ameliorate cognition deficits and attenuate brain oxidative damage induced by D-galactose in rats. AB - The aim of this study was to explore the neuroprotective effects of active compounds from Schisandra chinensis (Trucz.) Baill. (Magnoliaceae) against the D galactose (D-gal)-induced neurotoxicity in rat. The Wistar rats were subcutaneously injected with D-gal (150 mg/(kg day)) for six weeks and orally administered with water extract or 95 % ethanol extract (partitioned with petroleum ether (PE), chloroform (CF), ethyl acetate (EA) and n-Butanol (NB), respectively) of the fruits of Schisandra chinensis simultaneously. The alteration of cognitive functions was assessed by using Morris water maze and Step-down type passive avoidance test. The results demonstrated that PE fraction was the most effective fraction to ameliorate cognitive deficits. Further biochemical examination indicated that PE could attenuate the activities decreasing of superoxide dismutase (SOD), catalase (CAT), the total antioxidant (T-AOC) induced by D-gal, and maintain the normal levels of glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) in the serum, prefrontal cortex, striatum and hippocampus of the brain of related rat, selectively. Meanwhile, the compounds of PE fraction were also identified as mainly lignans, thus, these results suggest that lignans from the PE fraction of Schisandra chinensis represented a potential source of medicine for the treatment of the aging associated neurodegenerative diseases. PMID- 26847612 TI - Cellular phone collateral damage: A review of burns associated with lithium battery powered mobile devices. AB - AIM: The spontaneous destruction of lithium battery powered cellphones has raised concern about the safety of these devices. We present a case report and review of the literature of burn injuries sustained in association with cellular phone usage. METHODS: A Medline search was performed to identify articles describing cellular phone associated thermal injuries using key search words including "burn," "burn injury," "cellular phone," "cellphone," "thermal injury," and "telephone." Articles were reviewed for etiology, location, severity and treatment. We also present a case of a burn to the upper thigh resulting from cellular phone battery malfunction. RESULTS: Six case reports were identified detailing burn injuries obtained from cellphone use. Half of these cases occurred from battery malfunction with second degree being the most common severity. All cases were managed conservatively except one case, which required excision and primary closure. CONCLUSION: Lithium powered cellular phones are susceptible to overheating and destruction from inadequate heat dissipation during thermal runaway. This process can be initiated by local short-circuiting from direct contact with a low resistance conductor such as keys or coins. We reinforce the importance of safe cell phone battery practices including avoiding overcharging and direct skin exposure to minimize thermal injury risk. PMID- 26847611 TI - Neuron specific enolase: a promising therapeutic target in acute spinal cord injury. AB - Enolase is a multifunctional protein, which is expressed abundantly in the cytosol. Upon stimulatory signals, enolase can traffic to cell surface and contribute to different pathologies including injury, autoimmunity, infection, inflammation, and cancer. Cell-surface expression of enolase is often detected on activated macrophages, microglia/macrophages, microglia, and astrocytes, promoting extracellular matrix degradation, production of pro-inflammatory cytokines/chemokines, and invasion of inflammatory cells in the sites of injury and inflammation. Inflammatory stimulation also induces translocation of enolase from the cytosolic pool to the cell surface where it can act as a plasminogen receptor and promote extracellular matrix degradation and tissue damage. Spinal cord injury (SCI) is a devastating debilitating condition characterized by progressive pathological changes including complex and evolving molecular cascades, and insights into the role of enolase in multiple inflammatory events have not yet been fully elucidated. Neuronal damage following SCI is associated with an elevation of neuron specific enolase (NSE), which is also known to play a role in the pathogenesis of hypoxic-ischemic brain injury. Thus, NSE is now considered as a biomarker in ischemic brain damage, and it has recently been suggested to be a biomarker in traumatic brain injury (TBI), stroke and anoxic encephalopathy after cardiac arrest and acute SCI as well. This review article gives an overview of the current basic research and clinical studies on the role of multifunctional enolase in neurotrauma, with a special emphasis on NSE in acute SCI. PMID- 26847613 TI - A decade of burn unit experience with Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: Clinical pathological diagnosis and risk factor awareness. AB - Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN) is a rare and often fatal spectrum of mucocutaneous diseases usually attributable to severe adverse drug reactions. Burn units are referral centers for patients at the most extreme end of the disease continuum. Our burn center admits a much higher percentage of TEN (>30% BSA) cases than reported in most prior reviews. The purpose of this study was to analyze the diagnostic and prognostic value of variables collected on referred SJS/TEN patients. We retrospectively analyzed 94 patients admitted to our unit with a presumptive SJS/TEN diagnosis made in most cases by the referring center. Most of the diagnoses were clinical. Fifty of the 94 patients underwent biopsy when the clinical diagnosis was questionable. Of the 50 patients who underwent biopsy, 18 (36%) received an alternative diagnosis. Analysis was therefore limited to 76 patients, i.e. 44 patients felt to have firm clinical diagnoses plus 32 patients with diagnoses confirmed by biopsy. Mean age was 54.3 years (17-93) and overall gender ratio was 43 F vs. 33 M (56.6% vs. 43.4%). Mean LOS was 15.2 days (1-48) and overall mortality was 23.7% (18/76). Univariate analysis revealed percent body surface area (%BSA) did not show statistically significant association with mortality. Histopathological correlation for diagnosis is not standardized across institutions worldwide. Due to challenges in the diagnosis of SJS/TEN and the high incidence of error in clinical diagnosis, it is recommended that all patients with presumed SJS/TEN receive skin biopsies with H&E and direct immunofluorescence. We propose a diagnostic approach in order to address this need. Lack of association between %BSA and mortality suggests that all biopsy-proven SJS/TEN cases belong in specialty centers due to the unstable nature of the disease and risk for rapid progression. PMID- 26847614 TI - Imparting commercial antimicrobial dressings with low-adherence to burn wounds. AB - The objective of our study was to decrease the wound adherence of commercial silver based wound dressings by depositing a non-adherent layer. Our hypothesis was that this non-adherent layer will lower the dressing's adherence to burn wounds without compromising the antimicrobial activity or increasing the cytotoxicity. A polyacrylamide (PAM) hydrogel layer was grafted on two commercial silver antimicrobial dressings (silver nanocrystal dressing (NC) and silver plated dressing (SP)) using a proprietary technique. The grafted PAM served as the non-adherent layer. Dressing adherence was measured with a previously published in vitro gelatin model using an Instron mechanical force testing instrument. The dressings were challenged with two clinically retrieved bacterial strains (Methicillin-resistant Staphylococcus aureus (MRSA) and multidrug resistant (MDR) Pseudomonas aeruginosa) with both a disk diffusion test, and a suspension antibacterial test. The cytotoxicity of samples to human neonatal fibroblast cells was evaluated with 3-(4,5-dimethyl-2-thiazolyl)-2,5 diphenyltetrazolium bromide (MTT) assay. Both untreated dressings showed high peeling energy: 2070+/-453J/m(2) (NC) and 669+/-68J/m(2) (SP), that decreased to 158+/-119J/m(2) (NC) and 155+/-138J/m(2) (SP) with the PAM deposition. Addition of the PAM caused no significant difference in zone of inhibition (ZOI) (disk diffusion test) or antibacterial kinetics (suspension test) against both bacteria (p>0.05, n=6) in either dressing. Survival of fibroblasts was improved by the PAM grafting from 48+/-5% to 60+/-3% viable cells in the case of NC and from 55+/-8% to 61+/-4% viable cells in SP (p<0.05, n=12). It was concluded that PAM as a non adherent layer significantly decreases the adherence of these two commercial antimicrobial dressings in an in vitro gelatin model while preserving their antimicrobial efficacy, and reducing their cytotoxicity. PMID- 26847615 TI - A commercial transplant network's perspective of value in solid organ transplantation: Strategizing for value in transplant care. AB - INTRODUCTION: Solid organ transplantation has been an area of great interest to commercial payers ever since it moved into mainstream medical care beginning in the 1980s. Over the years a system of evaluating transplant program performance based on volume and one year graft and patient survival has developed. While this system has served its purpose, there is an increasing realization from payers that a need exists for a more sophisticated way to evaluate quality and cost effectiveness of these complex procedures. We report on the perspective of a large transplant network and its efforts to better understand the drivers of value over the entire continuum of care from referral through one year post transplant. METHODS: We evaluated members of a large commercial health plan who were referred for solid organ transplantation between January 1, 2010 and April 30, 2014. A total of 18,453 cases were evaluated for both clinical and economic outcomes. RESULTS: We report on two areas that can impact value over the entire continuum of care. Large variation in clinical practice and cost was noted. The observed variation was independent of inclusion in the transplant network's preferred network. The average pre-transplant and post-transplant costs for kidney, liver and heart transplantation cases at center level showed a variation of between 18 and 250% of the network's average. Clinical outcomes of median days on the waitlist, waitlist mortality and readmission within thirty days after transplant also showed wide variation. There was similar wide variation in cardiac evaluation of transplant candidates despite the existence of published recommendations. We demonstrated that pre-emptive renal transplantation is a high value strategy for this membership independent of donor source. CONCLUSION: In the studied population the data show wide variation in both clinical and economic parameters related to the transplant process in programs with statistically similar one year patient and graft survival. These results require further examination. In this era of increased concern about delivering value in medical care we may need to reassess how we evaluate organ transplantation programs. PMID- 26847616 TI - Bilateral partial miotomy of the puborectalis for dyssynergic defecation: an unaffordable risk. PMID- 26847617 TI - Laparoscopic versus open surgery for rectal cancer: a meta-analysis of 3-year follow-up outcomes. AB - PURPOSE: We wished to evaluate the effectiveness of laparoscopic and open surgery for patients with rectum cancer through a meta-analysis. METHODS: We searched PubMed, EMBASE, and Cochrane database until June 30, 2015, to identify eligible studies. Randomized controlled trials comparing laparoscopic with open surgery for rectum cancer were included. Meta-analysis was performed using the search strategy following the requirement of the Cochrane Library Handbook. Three-year overall survival (OS) and disease-free survival (DFS) were the main endpoints. RESULTS: Eight randomized controlled trials comprising 3145 patients matched the selection criteria. Meta-analysis showed no significant difference between laparoscopic and open surgery in 3-year overall survival (OS) and disease-free survival (DFS) (hazard ratio (HR)3-year OS = 0.83, 95 % CI [0.68-1.01]; P = 0.06; HR3-year DFS = 0.89, 95 % CI [0.75,1.05]; P = 0.16). No evidence of publication bias was observed. CONCLUSION: Our meta-analysis supported the notion that based on the 3-year DFS and OS, oncological outcomes are comparable after laparoscopic and open surgery for rectal cancer. PMID- 26847618 TI - Intravesical electromotive botulinum toxin type A administration for management of concomitant neuropathic bowel and bladder dysfunction in children. PMID- 26847619 TI - Impact of reassessment of colonic hyperplastic polyps by expert GI pathologists. AB - BACKGROUND: Recommended follow-up intervals after endoscopic removal of hyperplastic polyps (HP) and sessile serrated adenomas (SSA) differ because of assumed differences in biological behaviour. However, histopathologic differentiation is difficult, with higher SSA rates reported from specialist GI histopathologists. OBJECTIVE: The objective of this study was to clarify the relevance of histologic reassessment of HP. DESIGN AND SETTING: From a prospective screening colonoscopy study relevant serrated lesions (excluding distal small HP <=5 mm) diagnosed by private practice pathologists were reassessed by four specialized GI pathologists PATIENTS: One thousand sixty-nine screening colonoscopies were performed in patients. MAIN OUTCOME MEASUREMENTS: In terms of main outcome measurements, there is a likelihood of changes of the HP diagnosis on reassessment, as well as interrater variability. RESULTS: SSA were initially diagnosed in 7 cases (0.7%) and relevant HP in 83 (7.8%; 101 lesions). Of the latter, the chance of a change in diagnosis from HP to SSA by any of the four specialist histopathologists was higher for larger (>5 mm) and right-sided lesions (19.1 vs 1.3%, OR 18.4, p = 0.04) including a higher likelihood to change recommended follow-up intervals (32.1 vs 3.3%, p < 0.01). However, follow-up intervals were determined by concomitant adenomas in 41%. Interrater variability was also higher for these lesions (p = 0.04), with an overall kappa value of 0.48. However, this issue related to only 1.2% of the 1069 study cases. LIMITATION: The limitations this study are the limited case number as well as limited retrospective assessment. CONCLUSIONS: Right-sided HP >5 mm had a higher chance of change in diagnosis to SSA; therefore, they should probably be treated like adenomas and be removed. However, reliable data for recommendations on follow-up intervals of HP or SSA will require follow-up studies. PMID- 26847620 TI - Equivalent Helicobacter pylori infection rates in Lynch syndrome mutation carriers with and without a first-degree relative with gastric cancer. AB - BACKGROUND: Patients with Lynch syndrome (LS) are at an increased risk of developing gastric cancer. In 2010, a guideline that recommended to screen all patients for Helicobacter pylori was implemented in the Netherlands. H. pylori is an important risk factor in the development of gastric cancer in the general population, and eradication of the bacterium reduces this risk. We aimed to assess the proportion of LS patients being tested and the yield and also addressed the question whether H. pylori infection is more prevalent in LS families with known cases of gastric cancer. METHODS: Proven mutation carriers from five different Dutch hospitals were included. The implementation of H. pylori screening and its outcome was examined. The observation period was 2008 2013. The presence of first-degree family members with gastric cancer was noted, and it was observed if H. pylori infection was more prevalent in Lynch families with known cases of gastric cancer. Obtainable endoscopy reports were reviewed. RESULTS: Four hundred forty-three (male, 184) proven mutation carriers were included. The proportion of patients screened increased after 2010, from 37 to 68%. Twenty percent of the patients were infected. The 25 patients who had a first-degree family member with gastric cancer did not have a higher infection rate. In 30% of cases, an endoscopy was performed; in four patients, intestinal metaplasia and in eight patients, gastric cancer was found. CONCLUSION: The recommendation to screen for H. pylori is increasingly followed. The prevalence of infection in this patient group does not differ from the general population. Patients who had a first-degree family member with gastric cancer did not have a higher infection rate. PMID- 26847621 TI - Occurrence and predictors of recurrence after a first episode of acute venous thromboembolism: population-based Worcester Venous Thromboembolism Study. AB - Venous thromboembolism (VTE) has multiple risk factors and tends to recur. Despite the benefits of anticoagulation, the prevalence of, and case-fatality rate associated with, recurrent VTE remains a concern after an acute episode; it is particularly high during the acute treatment phase. We sought to quantify the magnitude, identify predictors, and develop risk score calculator of recurrence within 3 years after first-time VTE. This was a population-based surveillance study among residents of central Massachusetts (MA), USA, diagnosed with an acute first-time pulmonary embolism and/or lower-extremity deep vein thrombosis from 1999 to 2009 in hospital and ambulatory settings in all 12 central MA hospitals. Medical records were reviewed and validated. The 2989 study patients were followed for 5836 person-years [mean follow-up 23.4 (median 30) months]. Mean age was 64.3 years, 44 % were men, and 94 % were white. The cumulative incidence rate of recurrent VTE within 3 years after an index VTE was 15 % overall, and 25, 13, and 13 % among patients with active cancer, provoked, or unprovoked VTE, respectively. Multivariable regression indicated that active cancer, varicose vein stripping, and inferior vena cava filter placement were independent predictors of recurrence during both 3-month and 3-year follow-up. A risk score calculator was developed based on the 3-month prognostic model. In conclusion, the rate of VTE recurrence over 3 years of follow-up remained high. The risk score calculator may assist clinicians at the index encounter in determining the frequency of clinical surveillance and appropriate outpatient treatment of VTE during the acute treatment phase. PMID- 26847622 TI - Satiety Innovations: Food Products to Assist Consumers with Weight Loss, Evidence on the Role of Satiety in Healthy Eating: Overview and In Vitro Approximation. AB - The prevalence of overweight and obesity is increasing globally, driven by the availability of energy-dense palatable foods. Most dietary strategies fail because of hunger generated by calorie restriction, and interventions that specifically control hunger and/or promote fullness may aid success. Current consumers have a limited choice of satiety-enhancing products with proven health benefits, and innovative ways to produce new foods (as structural modification) to enhance satiety/satiation may provide new opportunities. However, this potential is hindered by the cost of product testing. Within the SATIN-SATiety INnovation project-an in vitro platform has been developed to offer a cost effective means of assessing the potential satiation/satiety effect of novel foods. This combines in vitro technologies to assess changes in colonic bacteria metabolism, appetite hormone release and the stability and bioavailability of active compounds in the new products/ingredients. This article provides a brief review of nutrients for which an impact on short-term appetite regulation has been demonstrated, and a summary of the changes to food structure which can be used to produce a change in appetite expression. Furthermore, the SATIN in vitro platform is discussed as a means of assessing the impact of nutritional and structural manipulations on appetite. PMID- 26847623 TI - Classical scrapie prions are associated with peripheral blood monocytes and T lymphocytes from naturally infected sheep. AB - BACKGROUND: Classical scrapie is a transmissible spongiform encephalopathy (TSE) that affects sheep and goats. Our previous bioassay studies in lambs revealed that scrapie prions could be detected in association with peripheral blood monocular cells (PBMC), B lymphocytes and platelet-rich plasma fractions. In the present study, bioassay in lambs was again used to determine if scrapie prions are associated with the other two subsets of PBMC, monocytes and T lymphocytes. RESULTS: PBMC, monocytes and T lymphocytes were isolated from two preclinically affected VRQ/VRQ sheep naturally infected with classical ovine scrapie and intravenously transfused into VRQ/VRQ lambs post-weaning. As determined using standard immunohistochemistry for scrapie, abnormal isoforms of prion protein were detected in lymphoid tissues of lambs inoculated with PBMC (4/4 recipient lambs), monocytes (2/5) and T lymphocytes (1/4). Prion protein misfolding activity was detected by serial protein misfolding cyclic amplification (sPMCA) in PBMC from monocyte and T lymphocyte recipient sheep in agreement with antemortem rectal biopsy results, but such prion protein misfolding activity was not detected from other recipients. CONCLUSIONS: These findings show that scrapie prions are associated with monocytes and T lymphocytes circulating in the peripheral blood of sheep naturally infected with classical scrapie. Combined with our previous findings, we can now conclude that all three major subsets of PBMC can harbor prions during preclinical disease and thus, present logical targets for development of a sensitive assay to detect scrapie prions. In this regard, we have also demonstrated that sPMCA can be used to detect scrapie prions associated with PBMC. PMID- 26847624 TI - Modified sonourethrography assists urethral catheterization. AB - Sonourethrography (SUG) is an infrequently used modality to observe the male urethra. We modified SUG to examine the reasons for difficulty in urethral catheterization and to determine a safe approach to resolve these problems. Following retrograde urethral jelly injection, modified SUG (mSUG) was performed in male patients with difficulty in urethral catheterization. mSUG was performed using transcutaneous ultrasonography in patients for whom the catheter became lodged in the penile urethra. In other patients, mSUG was performed using transrectal ultrasonography. We divided the causes of difficult indwelling urethral catheterization into physiological and pathological conditions. With regard to physiological conditions, the urethral catheter became stuck in the bulbous portion, membranous urethra, and prostatic urethra. mSUG distinguished the problematic part of the urethra in real time, and it assisted in overcoming the problem. With regard to pathological conditions, urethral stricture after trauma or surgery was clearly demonstrated in the penile and prostatic portions of the urethra. As with physiological conditions, mSUG images assisted in navigating the catheter through the problematic pathological areas or demonstrated the need to abandon the catheterization. mSUG can visualize the male urethra clearly during urethral catheterization and provide real-time assistance with the procedure. PMID- 26847625 TI - Maternal and foetal outcomes among 4118 women with HIV infection treated with lopinavir/ritonavir during pregnancy: analysis of population-based surveillance data from the national study of HIV in pregnancy and childhood in the United Kingdom and Ireland. AB - BACKGROUND: The National Study of HIV in Pregnancy and Childhood (NSHPC) conducts comprehensive population-based surveillance of pregnancies in women with HIV infection in the United Kingdom/Ireland. Use of antepartum antiretroviral therapy (ART) for prevention of mother-to-child transmission (MTCT) and to treat maternal infection, if required, is standard practise in this population; lopinavir/ritonavir (LPV/r) is commonly used. The study objective was to examine the use of LPV/r among pregnant women with HIV infection to describe maternal and foetal outcomes. METHODS: The NSHPC study collected maternal, perinatal and paediatric data through confidential and voluntary obstetric and paediatric reporting schemes. Pregnancies reported to the NSHPC by June 2013, due to deliver 2003-2012 and with LPV/r exposure were included in this analysis, using pregnancy as the unit of observation. RESULTS: Four thousand eight hundred sixty-four LPV/r exposed pregnancies resulting in 4702 deliveries in 4118 women were identified. Maternal region of birth was primarily sub-Saharan Africa (77 %) or United Kingdom/Ireland (14 %). Median maternal age at conception was 30 years. LPV/r was initiated preconception in 980 (20 %) and postconception in 3884 (80 %) pregnancies; median duration of antepartum LPV/r exposure was 270 and 107 days, respectively. Viral load close to delivery was <50 copies/mL in 73 % and <1000 copies/mL in 94 % of women. 63 % of deliveries were by caesarean section (elective, 6 %; emergency, 38 %). Among singleton live births, 13 % were <37 weeks of gestation (2.5 % <32 weeks) and 15 % had birth weight <2500 g (2.3 % <1500 g). MTCT rates were 1.1 (2003-2007) and 0.5 % (2008-2012). 134 live born children (2.9 %) had >=1 congenital abnormality. CONCLUSIONS: The results of this analysis using real-world data from a large number of pregnant women with HIV infection in the United Kingdom and Ireland who received LPV/r-containing ART regimens demonstrate that these regimens have a good safety profile and are effective for viral suppression during pregnancy, with associated low rates of MTCT. PMID- 26847626 TI - New pediatric vision screener, part II: electronics, software, signal processing and validation. AB - BACKGROUND: We have developed an improved pediatric vision screener (PVS) that can reliably detect central fixation, eye alignment and focus. The instrument identifies risk factors for amblyopia, namely eye misalignment and defocus. METHODS: The device uses the birefringence of the human fovea (the most sensitive part of the retina). The optics have been reported in more detail previously. The present article focuses on the electronics and the analysis algorithms used. The objective of this study was to optimize the analog design, data acquisition, noise suppression techniques, the classification algorithms and the decision making thresholds, as well as to validate the performance of the research instrument on an initial group of young test subjects-18 patients with known vision abnormalities (eight male and 10 female), ages 4-25 (only one above 18) and 19 controls with proven lack of vision issues. Four statistical methods were used to derive decision making thresholds that would best separate patients with abnormalities from controls. Sensitivity and specificity were calculated for each method, and the most suitable one was selected. RESULTS: Both the central fixation and the focus detection criteria worked robustly and allowed reliable separation between normal test subjects and symptomatic subjects. The sensitivity of the instrument was 100 % for both central fixation and focus detection. The specificity was 100 % for central fixation and 89.5 % for focus detection. The overall sensitivity was 100 % and the overall specificity was 94.7 %. CONCLUSIONS: Despite the relatively small initial sample size, we believe that the PVS instrument design, the analysis methods employed, and the device as a whole, will prove valuable for mass screening of children. PMID- 26847627 TI - Differences in the trajectory of bone mineral density change measured at the total hip and femoral neck between men and women following hip fracture. AB - Research has not examined changes in bone mineral density (BMD) between men and women following hip fracture. The aim was to evaluate sex differences in BMD following hip fracture. Men experienced significant declines in BMD, while not statistically greater than women, underscoring the necessity for better osteoporosis care in men. INTRODUCTION: Each year in the USA, approximately 260,000 older adults experience a hip fracture. Women experiencing hip fracture have excess decline in BMD in the year following fracture compared to expected decrements due to aging, but few studies have assessed sex differences in the sequelae of hip fracture. Thus, our objective was to examine sex differences in BMD change in the year after hip fracture. METHODS: The sample (n = 286) included persons enrolled in the Baltimore Hip Studies 7th cohort, a study that matched (1:1) men and women experiencing hip fracture. Weighted estimating equations that accounted for missing data and selective survival were used to estimate sex differences in 12-month total hip (TH) and femoral neck (FN) BMD changes. RESULTS: Men had larger average adjusted percent decline in TH and FN BMD. Adjusted 12-month decreases at the FN showed a statistically significant decline of -4.60% (95% confidence interval [CI] -7.76%, -0.20%) in men and an insignificant change of -1.62% (95% CI -4.57%, 1.32%) in women. Yet, the difference in change between men and women was not statistically significant (P = 0.17). The estimated sex differences for TH BMD loss were smaller in magnitude. CONCLUSIONS: There is evidence of significant BMD loss among men at the FN in the year after hip fracture. Although not statistically greater than women, these clinically significant findings highlight the need for improved osteoporosis care among men prior to and after hip fracture. PMID- 26847628 TI - Evaluation of osteoporosis risk and initiation of a nurse practitioner intervention program in an orthopedic practice. AB - The purpose of this study was to assess whether education and referral by a nurse practitioner could improve treatment adherence in patients with low bone mineral density in the orthopedic office. Our customized project did show some improvement but resistance to care continues in this unique population of patients. INTRODUCTION: Osteoporosis and osteopenia are significant clinical problems. Nearly 50% of adults over the age of 50 are osteopenic (Looker et al. in Osteoporos Int 22:541-549, 2011). Many patients with osteoporosis are not taking calcium or vitamin D, or any active treatment, even after dual energy X ray absorptiometry (DXA) and demonstration of low bone mineral density (Dell et al. in J Bone Joint Surg Am 91(Suppl 6):79-86, 2009). One hypothesis to explain low adherence with osteoporosis treatment is lack of patient education. This study was designed to compare a control group with an education-intervention group (receiving patient education from a nurse practitioner) to determine any effect of education on treatment adherence. METHODS: A total of 242 females and 105 males were studied as a control: a total of 292 females and 155 male were studied in the education group. Patients in the education group received educational materials and were counseled by a single nurse practitioner. Patients had a DXA performed and patients with osteoporosis or osteopenia were followed to assess treatment. At 12 months, patients received follow-up phone calls to determine patient use of calcium, vitamin D, and/or an active treatment. Results between the groups were compared. RESULTS: Significantly more patients began calcium and vitamin D after education (p = 0.04); significantly more patients were taking or were recommended for an active treatment after education (p = 0.03). Thirty percent of patients either did not follow up or refused active treatment for osteoporosis. Approximately 50% of patients with osteoporosis were not taking an FDA-approved pharmacologic agent for osteoporosis treatment, despite education. CONCLUSION: After patient education and referral to endocrinology, significantly more patients began calcium and vitamin D supplementation. However, up to 50% of patients with osteoporosis would not complete follow-up visits and/or did not adhere to treatment recommendations for osteoporosis. PMID- 26847629 TI - Correspondence on "Microgravity Reduces the Differentiation and Regenerative Potential of Embryonic Stem Cells". PMID- 26847630 TI - Ticks and tick-borne pathogens in wild birds in Greece. AB - Wild birds are common hosts of ticks and can transport them for long distances, contributing to the spreading of tick-borne pathogens. The information about ticks on birds and tick-borne pathogens in Greece is limited. The present study aimed to evaluate the prevalence and species of ticks infesting wild resident birds (mostly small passerines) in Greece, and to assess Borrelia and Rickettsia infection in the collected ticks. Detection of Borrelia burgdorferi s.l. was performed by nested PCR targeting the flaB gene. Rickettsia spp. were detected by PCR targeting the gltA and ompA genes. Seven (2 %) out of 403 birds examined in northern Greece in 2013 were infested with 15 ticks, identified as Ixodes frontalis, Ixodes acuminatus, Hyalomma marginatum, Hyalomma aegyptium and Hyalomma sp. All ticks were negative for Borrelia spp. while four of them were positive for rickettsiae (Rickettsia aeschlimannii in H. aegyptium and Rickettsia sp. in I. frontalis, H. aegyptium and H. marginatum). Ixodes acuminatus is reported for the first time in Greece and Sylvia borin is reported as a new host record for I. acuminatus. PMID- 26847631 TI - Besnoitia besnoiti infections activate primary bovine endothelial cells and promote PMN adhesion and NET formation under physiological flow condition. AB - Besnoitia besnoiti is an obligate intracellular and emerging coccidian parasite of cattle that mainly infects host endothelial cells during acute infection. We here analyzed early innate immune reactions of B. besnoiti-infected primary bovine umbilical vein endothelial cells (BUVEC). B. besnoiti infections significantly activated BUVEC since the gene transcripts of several adhesion molecules (P-selectin, intercellular adhesion molecule 1(ICAM-1)), chemokines (CXCL1, CXCL8, CCL5), and of COX-2 were significantly upregulated during in vitro infection. Overall, the highest upregulation of most transcripts was observed at 24 or 48 h post infection (p.i.). Enhanced adhesion molecule expression in infected host cells was confirmed by PMN adhesion assays being performed under physiological flow conditions revealing a significantly increased PMN adhesion on B. besnoiti-infected BUVEC layers at 24 h p.i. Furthermore, we were able to illustrate neutrophil extracellular traps (NETs) being released by PMN under physiological flow conditions after adhesion to B. besnoiti-infected BUVEC layers. The present study shows that B. besnoiti infections of primary BUVEC induce a cascade of pro-inflammatory reactions and triggers early innate immune responses. PMID- 26847633 TI - Lesion filling effect in regional brain volume estimations: a study in multiple sclerosis patients with low lesion load. AB - INTRODUCTION: Regional brain volume estimation in multiple sclerosis (MS) patients is prone to error due to white matter lesions being erroneously segmented as grey matter. The Lesion Segmentation Toolbox (LST) is an automatic tool that estimates a lesion mask based on 3D T2-FLAIR images and then uses this mask to fill the structural MRI image. The goal of this study was (1) to test the LST for estimating white matter lesion volume in a cohort of MS patients using 2D T2-FLAIR images, and (2) to evaluate the performance of the optimized LST on image segmentation and the impact on the calculated grey matter fraction (GMF). METHODS: The study included 110 patients with a clinically isolated syndrome and 42 with a relapsing-remitting MS scanned on a 3.0-T MRI system. In a subset of consecutively selected patients, the lesion mask was semi-manually delineated over T2-FLAIR images. After establishing the optimized LST parameters, the corresponding regional fractions were calculated for the original, filled, and masked images. RESULTS: A high agreement (intraclass correlation coefficient (ICC) = 0.955) was found between the (optimized) LST and the semi-manual lesion volume estimations. The GMF was significantly smaller when lesions were masked (mean difference -0.603, p < 0.001) or when the LST filling technique was used (mean difference -0.598, p < 0.001), compared to the GMF obtained from the original image. CONCLUSION: LST lesion volume calculation seems reliable. GMFs are significantly reduced when a method to correct the contribution of MS lesions is used, and it may have an impact in assessing GMF differences between clinical cohorts. PMID- 26847632 TI - Henneguya paraensis n. sp. (Myxozoa; Myxosporea), a new gill parasite of the Amazonian fish Cichla temensis (Teleostei: Cichlidae): morphological and molecular aspects. AB - The present study describes light microscopy, transmission electron microscopy, and molecular analyses of a myxosporid found parasitizing the gill region of the teleost fish Cichla temensis, collected from the Tocantins River, near Cameta, Para State, Brazil. The prevalence of infection was 60 %. The spore-containing cysts that were located in the gill lamellae were oval and whitish. The spores had a mean length of 42.3 +/- 0.65 MUm; fusiform body, 12.8 +/- 0.42-MUm long and 8.6 +/- 0.32-MUm wide; each of the two valves exhibited a tapering tail of 29.5 +/- 0.73 MUm length. The spores had two polar capsules, 7.4 +/- 0.16-MUm long by 2.6 +/- 0.08-MUm wide, containing a polar filament with 5-7 twists. The spores differ from the species previously described, and phylogenetic analysis based on spore morphology and molecular aspects indicated that the fish parasite Henneguya sp. has a strong trend to form clades mainly based on the environment and host order/family. Thus, we conclude that the species belongs to the family Myxobolidae, genus Henneguya, which comprises a new species: Henneguya paraensis n. sp. PMID- 26847634 TI - Kruppel-like factor 4 expression in oral carcinoma cells and hypermethylation at the gene promoter. AB - BACKGROUND: Kruppel-like factor 4 (KLF4) is a transcription factor regulating proliferation-differentiation balance of epithelium, and down-regulated in less differentiated and advanced oral carcinomas. Although the expression is inactivated by the promoter hypermethylation in malignant tumor cells, it remains unknown in oral carcinoma cells. METHODS: Genomic DNA isolated from nine different oral carcinoma cell lines and a normal keratinocyte line was treated with sodium bisulfite, and methylation at KLF4 gene promoter was determined by PCR direct-sequence analysis. KLF4 expression in cells cultured with or without demethylation reagent was monitored by quantitative real-time PCR and immunoblot. RESULTS: A 237-bp promoter region spanning - 718 and - 482 of KLF4 gene was hypermethylated in oral carcinoma cells that express KLF4 at a low level, but the methylation was infrequent in cells expressing KLF4 high amount. The downstream region from - 481 to +192 was not methylated in any cell lines. Demethylation treatment of cells up-regulated the expression at mRNA and protein levels. CONCLUSION: This study demonstrated that hypermethylation at a narrow range of the promoter region down-regulates KLF4 expression, and suggests that the loss of expression by the hypermethylation contributes to oral carcinoma progression. PMID- 26847635 TI - Surgical treatment of mucoepidermoid carcinoma of the lung: 20 years' experience. AB - BACKGROUND: Pulmonary mucoepidermoid carcinoma is a rare salivary gland-type neoplasm. We aimed to elucidate the optimal management of this rare condition by reviewing the treatment outcomes of patients at our institution with mucoepidermoid carcinoma of the lung. METHODS: We performed a retrospective review of all patients with pulmonary mucoepidermoid carcinoma who underwent surgical treatment between January 1993 and December 2012. We reviewed the patients' clinical characteristics and the therapeutic interventions undertaken. RESULTS: Nine patients were evaluated in this study, 7 of whom were female. The median age of all patients was 54 years (range 10-72 years). Six patients had tumors of a low histologic grade, and the other 3 had high-grade malignancies. Prior to surgery, 2 patients required endobronchial intervention for obstructive pneumonia. Eight patients underwent lobectomy, and one had a bilobectomy. Two patients required bronchoplasty, and one required resection of the left atrium for complete resection of the primary neoplasm. Two patients with advanced disease and high-grade tumors died due to cancer progression. The overall 5-year survival rate was 72.9%. One patient with a high-grade malignancy demonstrated exon 21 mutation of the epidermal growth factor receptor gene. CONCLUSIONS: Complete surgical resection is important for long-term survival in patients with pulmonary mucoepidermoid carcinoma. The techniques of bronchoplasty and extended resection may contribute to better surgical management of this disease. Endobronchial interventions may be considered for the management of obstructive pneumonia prior to surgery. PMID- 26847637 TI - Triaging Psychiatric Care: Risk Assessment Construction and Validation for Washington's Involuntary Treatment and Forensic Commitment Populations. AB - There is a growing need in Washington to triage patients being considered for inpatient treatment. There has previously been no risk assessment normed to persons with mental illness in the State of Washington. The Static Risk Assessment (SRA) is used in Washington to assess risk among offenders under State Department of Corrections supervision. The present study sought to create and validate a new risk assessment, the SRA for Mental Health Patients (SRA-MHP), for two mental health populations in Washington. A sample of 16,289 patients involuntarily committed due to being deemed dangerous or gravely disabled, as well as a sample of 8,713 forensic patients undergoing a competency evaluation to stand trial after being charged with a crime, was gathered to assess the utility in applying the SRA-MHP to persons with mental illness. Results indicate that the SRA-MHP has high predictive performance for these samples. PMID- 26847636 TI - PET imaging of epidermal growth factor receptor expression in tumours using 89Zr labelled ZEGFR:2377 affibody molecules. AB - Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor, which is overexpressed in many types of cancer. The use of EGFR targeting monoclonal antibodies and tyrosine-kinase inhibitors improves significantly survival of patients with colorectal, non-small cell lung cancer and head and neck squamous cell carcinoma. Detection of EGFR overexpression provides important prognostic and predictive information influencing management of the patients. The use of radionuclide molecular imaging would enable non invasive repeatable determination of EGFR expression in disseminated cancer. Moreover, positron emission tomography (PET) would provide superior sensitivity and quantitation accuracy in EGFR expression imaging. Affibody molecules are a new type of imaging probes, providing high contrast in molecular imaging. In the present study, an EGFR-binding affibody molecule (ZEGFR:2377) was site specifically conjugated with a deferoxamine (DFO) chelator and labelled under mild conditions (room temperature and neutral pH) with a positron-emitting radionuclide (89)Zr. The (89)Zr-DFO-ZEGFR:2377 tracer demonstrated specific high affinity (160 +/- 60 pM) binding to EGFR-expressing A431 epidermoid carcinoma cell line. In mice bearing A431 xenografts, (89)Zr-DFO-ZEGFR:2377 demonstrated specific uptake in tumours and EGFR-expressing tissues. The tracer provided tumour uptake of 2.6 +/- 0.5% ID/g and tumour-to-blood ratio of 3.7 +/- 0.6 at 24 h after injection. (89)Zr-DFO-ZEGFR:2377 provides higher tumour-to-organ ratios than anti-EGFR antibody (89)Zr-DFO-cetuximab at 48 h after injection. EGFR expressing tumours were clearly visualized by microPET using (89)Zr-DFO ZEGFR:2377 at both 3 and 24 h after injection. In conclusion, 8(9)Zr-DFO ZEGFR:2377 is a potential probe for PET imaging of EGFR-expression in vivo. PMID- 26847638 TI - Addicted to Pain: A Preliminary Model of Sexual Masochism as Addiction. AB - An exploratory, qualitative, phenomenological study focused on the experience of pain while participating in sexual masochistic acts. Semi-structured interviews were conducted with nine individuals (four female, five male) who regularly participate in sexually masochistic acts and point to pain as central to their experience. Qualitative analysis of the data revealed several key characteristics of the participant's experience: the first time, intoxication, craving and withdrawal, tolerance, pain as control, and the pain inducing partner. The findings indicate that the way pain is experienced while mitigated through masochistic behavior creates an addictive process that coincides with a chronic behavioral spin contextualization. This article presents a preliminary model of addiction to physical pain in light of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) definition of substance-related and addictive disorders and the behavioral spin theory. PMID- 26847639 TI - Streptococcus pneumoniae and Haemophilus species colonization in health care workers: the launch of invasive infections? AB - BACKGROUND: Streptococcus pneumoniae and Haemophilus influenzae are important human pathogens. The risk of airborne and droplet-transmitted respiratory tract infections in healthcare workers (HCW) is substantial. The aim of this study was to determine the extent of oropharyngeal colonization with S. pneumoniae and Haemophilus spp. their antibiogram and risk factors of colonization in HCW at a tertiary care center, Western Nepal. METHODS: During 3 month period, 100 oropharyngeal swab specimens were collected from HCW of Manipal Teaching Hospital and 50 from non HCW from community. All the 150 specimens were screened for Haemophilus spp. and S. pneumoniae by standard techniques. Serotyping of H. influenzae type b was done by using specific antiserum. Antibiotic sensitivity patterns of isolates were determined by modified Kirby Bauer disc diffusion method. Association between the groups was analyzed using the Pearson chi(2) test and Fisher exact test. A forward step logistic regression model was used to identify significant predictors for colonization. RESULT: Sixty-five percent of HCW were colonized with S. pneumoniae and/or Haemophilus species compared to 32 % of non-HCW. Health care workers had odd ratio (OR) 3.946 [CI (1.916, 8.128)] times more tendency of colonization compared to non-HCW (P < 0.05). Pneumococcal colonization was observed high among smokers (81.5 %). Amongst HCW, post graduate resident doctors had higher rate of colonization (83.3 %) followed by interns (64.9 %), least being amongst the laboratory workers (58.3 %). CONCLUSION: The higher rate of colonization amongst HCW raises the possibility of occupational risk as well as horizontal spread of infections. PMID- 26847640 TI - Second-hand smoke in four English prisons: an air quality monitoring study. AB - BACKGROUND: To measure levels of indoor pollution in relation to smoking in four English prisons. METHODS: TSI SidePak AM510 Personal Aerosol Monitors were used to measure concentrations of particulate matter less than 2.5 MUm in diameter (PM2.5) for periods of up to 9 h in selected smoking and non-smoking areas, and personal exposure monitoring of prison staff during a work shift, in four prisons. RESULTS: PM2.5 data were collected for average periods of 6.5 h from 48 locations on 25 wing landings where smoking was permitted in cells, on 5 non smoking wings, 13 prisoner cells, and personal monitoring of 22 staff members. Arithmetic mean PM2.5 concentrations were significantly higher on smoking than non-smoking wing landings (43.9 MUg/m(3) and 5.9 MUg/m(3) respectively, p < 0.001) and in smoking than non-smoking cells (226.2 MUg/m(3) and 17.0 MUg/m(3) respectively, p < 0.001). Staff members wore monitors for an average of 4.18 h, during which they were exposed to arithmetic mean PM2.5 concentration of 23.5 MUg/m(3). CONCLUSIONS: The concentration of PM2.5 pollution in smoking areas of prisons are extremely high. Smoking in prisons therefore represents a significant health hazard to prisoners and staff members. PMID- 26847643 TI - Evidence that Dry January changes behaviour for good. PMID- 26847641 TI - Surveillance of maternal antibodies against West Nile virus in chicken eggs in South-West Germany. AB - OBJECTIVE: The emergence of West Nile virus (WNV) in several European countries increases the risk of its introduction to Germany. This study evaluated a new method for WNV surveillance by testing for maternal antibodies in chicken eggs. METHODS: A total of 1,990 eggs were collected in 35 sampling sites in the south west of Germany and tested for WNV-specific antibodies. RESULTS: The results did not indicate evidence for WNV circulation in the study area. CONCLUSION: This work serves as a proof-of-concept that such a method is useful and a potential alternative to use of sentinel chicken for regular WNV surveillance. PMID- 26847645 TI - c-Jun N-terminal kinase activation by nitrobenzoxadiazoles leads to late-stage autophagy inhibition. AB - BACKGROUND: Nitrobenzoxadiazole derivatives (NBDs), including NBDHEX and the recently developed MC3181, are promising anticancer agents able to target glutathione transferase and inhibit both its catalytic activity and ability to sequester TNF-receptor associated factor 2 (TRAF2) and c-Jun N-terminal kinase (JNK). NBDs have been shown to impair the growth and survival of a broad-spectrum of tumor types, in vitro and in vivo. Herein, we evaluated the effects of the new compound MC3181 on U-2OS osteosarcoma cells and investigated the impact of both NBDHEX and MC3181 on autophagy. METHODS: Cell viability was evaluated by sulforhodamine B assay. The dissociation of the TRAF2-GSTP1-1 complex was detected by proximity ligation assay, while the phospho-activation of JNK was assessed by western blotting. The effects of NBDs on autophagy were evaluated by GFP-LC3 puncta formation, western blotting for LC3-II and p62, and LC3 turnover assay in the presence of bafilomycin A1. The role of JNK in the reduction of autophagic flux caused by NBDs was investigated using JNK1 shRNA-transfected cells. Fluorogenic caspase activity assay and flow cytometric analysis of DNA content were used to determine the cytotoxic effects of NBDs on JNK1-silenced cells. RESULTS: Similar to NBDHEX, MC3181 reduced viability and activated TRAF2/JNK signaling in U-2OS cells. Moreover, NBDs induced the accumulation of autophagic vesicles and LC3-II while reducing both basal and nutritional stress induced autophagic flux. Furthermore, increased levels of both LC3-II and the autophagy selective substrate p62 were observed in different tumor cell lines treated with NBDs, the concurrent increase of these markers being consistent with an impairment of autophagosome clearance. Autophagy inhibition by NBDs required JNK activity: NBDs caused autophagy inhibition and caspase-3 activation in JNK positive U-2OS, but no autophagic flux inhibition or caspase-3 activation in JNK silenced cells. CONCLUSIONS: Our demonstration that NBDs can act as late-phase autophagy inhibitors opens new opportunities to fully exploit their therapeutic potential. This may not rely solely on their effectiveness in inducing cell cycle arrest and apoptosis, but also on their ability to weaken the capacity of tumor cells to endure stress conditions via autophagy. In addition, this study provides evidence that JNK can participate in impairing autophagy. PMID- 26847647 TI - Experimental Biology for the Identification of Causal Pathways in Atherosclerosis. AB - More than 60 genomic loci have been implicated by genome-wide association studies (GWAS) and exome-wide association studies as conferring an increased risk of myocardial infarction and coronary artery disease (CAD). However, the causal gene and variant is often unclear. Using the functional analysis of genetic variants in experimental animal models, we anticipate understanding which candidate gene at a specific locus is associated with atherosclerosis and revealing the underlying molecular and cellular mechanisms, ultimately leading to the identification of causal pathways in atherosclerosis and may provide novel therapeutic targets for the treatment of atherosclerotic cardiovascular disease. PMID- 26847646 TI - Distribution and haplotype diversity of WKS resistance genes in wild emmer wheat natural populations. AB - KEY MESSAGE: The wheat stripe rust resistance gene Yr36 ( WKS1 ) with a unique kinase-START domain architecture is highly conserved in wild emmer wheat natural populations. Wild emmer wheat (Triticum dicoccoides) populations have developed various resistance strategies against the stripe rust pathogen Puccinia striiformis f. sp. tritici (Pst). The wild emmer gene, Yr36 (WKS1), which confers partial resistance to a broad spectrum of Pst races, is composed of a kinase and a START lipid-binding domain, a unique gene architecture found only in the Triticeae tribe. The analysis of 435 wild emmer accessions from a broad range of natural habitats revealed that WKS1 and its paralogue WKS2 are present only in the southern distribution range of wild emmer in the Fertile Crescent, supporting the idea that wheat domestication occurred in the northern populations. An analysis of full-length WKS1 sequence from 54 accessions identified 15 different haplotypes and very low-nucleotide diversity (pi = 0.00019). The high level of WKS1 sequence conservation among wild emmer populations is in contrast to the high level of diversity previously observed in NB-LRR genes (e.g., Lr10 and Pm3). This phenomenon may reflect the different resistance mechanisms and different evolutionary pathways that shaped these genes, and may shed light on the evolution of genes that confer partial resistance to stripe rust. Only five WKS1 coding sequence haplotypes were revealed among all tested accessions, encoding four different putative WKS1 proteins (designated P0, P1, P2, and P3). Infection tests showed that P0, P1, and P3 haplotypes display a resistance response, while P2 displayed a susceptible response. These results show that the WKS1 proteins (P0, P1, and P3) can be useful to improve wheat resistance to stripe rust. PMID- 26847648 TI - Detection and characterization of diverse alpha- and betacoronaviruses from bats in China. AB - Bats have been implicated as important reservoir hosts of alpha- and betacoronaviruses. In this study, diverse coronaviruses (CoVs) were detected in 50 of 951 (positive rate 5.3%) intestinal specimens of eight bat species collected in four provinces and the Tibet Autonomous Region of China by pan coronavirus RT-PCR screening. Based on 400-nt RNA-dependent RNA polymerase (RdRP) sequence analysis, eight belonged to genus Alphacoronavirus and 42 to Betacoronavirus. Among the 50 positive specimens, thirteen gave rise to CoV full length RdRP gene amplification for further sequence comparison, of which three divergent sequences (two from a unreported province) were subjected to full genome sequencing. Two complete genomes of betacoronaviruses (JTMC15 and JPDB144) and one nearly-complete genome of alphacoronavirus (JTAC2) were sequenced and their genomic organization predicted. The present study has identified additional numbers of genetically diverse bat-borne coronaviruses with a wide distribution in China. Two new species of bat CoV, identified through sequence comparison and phylogenetic analysis, are proposed. PMID- 26847649 TI - Identification and characterization of two human immunodeficiency virus type 1 unique recombinant forms from Yunnan, China. PMID- 26847651 TI - Fatigue rate of the external anal sphincter in elderly men. PMID- 26847650 TI - Molecular mechanisms of coronavirus RNA capping and methylation. AB - The 5'-cap structures of eukaryotic mRNAs are important for RNA stability, pre mRNA splicing, mRNA export, and protein translation. Many viruses have evolved mechanisms for generating their own cap structures with methylation at the N7 position of the capped guanine and the ribose 2'-Oposition of the first nucleotide, which help viral RNAs escape recognition by the host innate immune system. The RNA genomes of coronavirus were identified to have 5'-caps in the early 1980s. However, for decades the RNA capping mechanisms of coronaviruses remained unknown. Since 2003, the outbreak of severe acute respiratory syndrome coronavirus has drawn increased attention and stimulated numerous studies on the molecular virology of coronaviruses. Here, we review the current understanding of the mechanisms adopted by coronaviruses to produce the 5'-cap structure and methylation modification of viral genomic RNAs. PMID- 26847652 TI - A betabaculovirus encoding a gp64 homolog. AB - BACKGROUND: A betabaculovirus (DisaGV) was isolated from Diatraea saccharalis (Lepidoptera: Crambidae), one of the most important insect pests of the sugarcane and other monocot cultures in Brazil. RESULTS: The complete genome sequence of DisaGV was determined using the 454-pyrosequencing method. The genome was 98,392 bp long, which makes it the smallest lepidopteran-infecting baculovirus sequenced to date. It had a G + C content of 29.7% encoding 125 putative open reading frames (ORF). All the 37 baculovirus core genes and a set of 19 betabaculovirus specific genes were found. A group of 13 putative genes was not found in any other baculovirus genome sequenced so far. A phylogenetic analysis indicated that DisaGV is a member of Betabaculovirus genus and that it is a sister group to a cluster formed by ChocGV, ErelGV, PiraGV isolates, ClanGV, CaLGV, CpGV, CrleGV, AdorGV, PhopGV and EpapGV. Surprisingly, we found in the DisaGV genome a G protein-coupled receptor related to lepidopteran and other insect virus genes and a gp64 homolog, which is likely a product of horizontal gene transfer from Group 1 alphabaculoviruses. CONCLUSION: DisaGV represents a distinct lineage of the genus Betabaculovirus. It is closely related to the CpGV-related group and presents the smallest genome in size so far. Remarkably, we found a homolog of gp64, which was reported solely in group 1 alphabaculovirus genomes so far. PMID- 26847653 TI - Association between personality traits and mental health outcomes in older adults with lifetime trauma exposure: a nationwide community sample. AB - BACKGROUND: This study evaluated the impacts of earlier traumatic events on the mental health of older adults, in terms of mental disorders and mental well being, according to sociodemographic variables, trauma-related characteristics, and personality traits in a nationally representative sample of older Koreans. METHODS: A total of 1,621 subjects aged 60 to 74 years from a Korean national epidemiological survey of mental disorders responded face-to-face interviews. The Korean Composite International Diagnostic Interview was used to investigate lifetime trauma exposure (LTE) and psychiatric diagnoses. The EuroQol health classification system and life satisfaction scale were used to assess quality of life (QoL), and the Big Five Inventory-10 (BFI-10) to measure personality traits. RESULTS: Five-hundred and seventy-seven subjects (35.6%) reported a history of LTE (mean age at trauma, 30.8 years old). Current mental disorders were more prevalent in elderly people with LTE, while better current QoL was more frequent in those without LTE. Among older people with LTE, lower extraversion and higher neuroticism increased the risk of current mood or anxiety disorders, whereas higher extraversion increased the probability of experiencing mental well-being after adjusting for sociodemographic and trauma-related variables. CONCLUSION: Personality traits, especially extraversion, and neuroticism, may be useful for predicting the mental health outcomes of LTE in older adults. Further longitudinal studies investigating the relationship between traumatic events and mental health outcomes are needed. PMID- 26847654 TI - Cell-Free DNA as a Diagnostic Tool for Human Parasitic Infections. AB - Parasites often cause devastating diseases and represent a significant public health and economic burden. More accurate and convenient diagnostic tools are needed in support of parasite control programmes in endemic regions, and for rapid point-of-care diagnosis in nonendemic areas. The detection of cell-free DNA (cfDNA) is a relatively new concept that is being applied in the current armamentarium of diagnostics. Here, we review the application of cfDNA detection with nucleic acid amplification tests for the diagnosis and evaluation of different human parasitic infections and highlight the significant benefits of the approach using non-invasive clinical samples. PMID- 26847655 TI - Androgen ablation elicits PP1-dependence for AR stabilization and transactivation in prostate cancer. AB - BACKGROUND: Previous reports have documented protein phosphatase 1 (PP1) as an essential androgen receptor (AR) activator. However, more systemic studies are needed to further define PP1 effects on AR, particularly in the settings of prostate cancer cells and under conditions mimicking androgen ablation. METHODS: PP1 effects on AR protein expression, degradation, ubiquitination, and stabilization were examined in non-prostate cancer cells, followed by validation on exogenous settings in androgen-sensitive (LNCaP and VCaP) and castration resistant (C4-2) prostate cancer cells. Effects of PP1 on AR protein expression, on AR-mediated transcription of exogenous reporter and endogenous gene, and on LNCaP and C4-2 cell proliferation were monitored under androgen-containing versus androgen-depleted conditions to assess the effects of PP1 on AR responsiveness to androgen. RESULTS: In this report, we determined that PP1 functions to stabilize AR proteins that exclusively undergo the proteasome-dependent degradation, and the stimulatory effects of PP1 were predominantly mediated by the AR ligand binding domain (LBD). Consistently, PP1 enhances AR protein stability by disrupting the LBD-mediated and K48-linked ubiquitination cascade. We further validated the above findings in the prostate cancer cells by showing that PP1 inhibition can increase ubiquitin- and proteasome-dependent degradation of endogenous AR under androgen deprivation. Significantly, we found that PP1 could markedly activate AR transcriptional activities under conditions mimicking androgen ablation and that androgen sensitivity was substantially evoked by PP1 inhibition in the prostate cancer cell lines. CONCLUSIONS: As summarized in a simplified model, our studies defined an essential PP1-mediated pathway for AR protein stabilization that can compensate the loss of androgen and established a mechanistic link between PP1 and androgen responsiveness. The amplified PP1 dependence for AR activation under the androgen ablated conditions provides a rationale to therapeutically target the PP1-AR module in the castration-resistant prostate cancer (CRPC). Our findings also suggested an alternative AR-targeting compounds screening strategy that aims to circumvent PP1-AR interaction. PMID- 26847656 TI - Absolute quantification of imipramine and its metabolites in vivo utilizing calibrators from radiolabeled in vitro incubations. AB - BACKGROUND: We have demonstrated the use of a single-point calibration approach, derived from in vitro metabolite identification studies utilizing radiolabeled imipramine, that allows for the quantitation of metabolites from in vivo studies in the absence of metabolite synthetic standards. RESULTS: From the in vivo study of imipramine in rats, the concentration of parent and metabolites were determined using the single-point calibration approach. Sixty seven percent of the dosed imipramine was recovered within 24 h, with 95 and 5% of drug-related material detected in feces and urine, respectively. CONCLUSION: Using a novel single-point calibration approach from radiolabeled in vitro studies, we quantified metabolites in vivo and determined various disposition pathways. PMID- 26847657 TI - Origins of Large Voltage Hysteresis in High-Energy-Density Metal Fluoride Lithium Ion Battery Conversion Electrodes. AB - Metal fluorides and oxides can store multiple lithium ions through conversion chemistry to enable high-energy-density lithium-ion batteries. However, their practical applications have been hindered by an unusually large voltage hysteresis between charge and discharge voltage profiles and the consequent low energy efficiency (<80%). The physical origins of such hysteresis are rarely studied and poorly understood. Here we employ in situ X-ray absorption spectroscopy, transmission electron microscopy, density functional theory calculations, and galvanostatic intermittent titration technique to first correlate the voltage profile of iron fluoride (FeF3), a representative conversion electrode material, with evolution and spatial distribution of intermediate phases in the electrode. The results reveal that, contrary to conventional belief, the phase evolution in the electrode is symmetrical during discharge and charge. However, the spatial evolution of the electrochemically active phases, which is controlled by reaction kinetics, is different. We further propose that the voltage hysteresis in the FeF3 electrode is kinetic in nature. It is the result of ohmic voltage drop, reaction overpotential, and different spatial distributions of electrochemically active phases (i.e., compositional inhomogeneity). Therefore, the large hysteresis can be expected to be mitigated by rational design and optimization of material microstructure and electrode architecture to improve the energy efficiency of lithium-ion batteries based on conversion chemistry. PMID- 26847658 TI - Unraveling the Mechanism of Dyskinesia One Transcription Factor at a Time. PMID- 26847659 TI - What Makes You Tic? A New Lead in Tourette Syndrome Genetics. PMID- 26847660 TI - Deep Brain Stimulation for Tourette Syndrome: Lessons Learned and Future Directions. PMID- 26847661 TI - Twin Reversed Arterial Perfusion Sequence (TRAPS): An Illustrative Series of 13 Cases. AB - Twin reversed-arterial-perfusion sequence (TRAPS) is a rare and severe complication of monochorionic twin pregnancies. It usually occurs in the setting of monochorionic placentation, when the heart of a normal appearing twin serves as the pump for one or more dysmorphic twins whose head, thoracic organs, and upper extremities do not fully develop or do not develop at all and thus lack cardiac activity. Anomalous vascular placental architecture causes a shift in arterial flow towards the acardiac twin(s). The exact physiopathologic mechanisms that lead to this devastating phenomenon are not well known. We reviewed the maternal history and the surgical pathology reports of the fetuses and placentas of 13 different cases of TRAPS that were collected in a 23-year study period at a single institution. Herein we summarize the characteristic findings and illustrate specific mechanical feto-placental circulation issues that appear to be instrumental in the development of TRAPS. PMID- 26847662 TI - Association Between BCR-ABL Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia and Cardiovascular Events, Major Molecular Response, and Overall Survival: A Systematic Review and Meta-analysis. AB - Importance: A phase 3 trial with ponatinib in patients with chronic myeloid leukemia (CML) was interrupted due to an important increase of vascular occlusive events. A similar risk was also suspected with nilotinib, another BCR-ABL tyrosine kinase inhibitor (TKI) used in patients with CML. Objective: To assess the risk of vascular occlusive events in patients with CML treated by new generations of TKIs and provide an overall assessment of the clinical benefit. Data Sources: Two independent reviewers selected studies from PubMed, Scopus, and the Cochrane library database from their inception to October 21, 2014. Abstracts published during the past 3 years at international congresses and a trial register were also searched. Study Selection: Two independent reviewers screened abstracts and titles against inclusion and exclusion criteria published previously in the PROSPERO 2014 protocol: CRD42014014147. Among the 249 abstracts identified, 10 studies fulfilled the established criteria. Data Extraction and Synthesis: Two investigators independently extracted data using a standard form. Main Outcomes and Measures: Information extracted included study and patients characteristics, type of intervention and data on vascular occlusive events, overall survival, and major molecular response (MMR). The meta-analysis was performed using a fixed-effects model. Odds ratios (ORs) with 95% CIs were computed using the Peto method. Results: Ten randomized clinical trials (3043 patients) were analyzed. Risk of vascular occlusive events was increased with dasatinib (OR, 3.86; 95% CI, 1.33-11.18), nilotinib (OR, 3.42; 95% CI, 2.07 5.63), and ponatinib (OR, 3.47; 95% CI, 1.23-9.78) compared with imatinib in patients with CML. No significant difference was found with bosutinib (OR, 2.77; 95% CI, 0.39-19.77). New-generation TKIs increased the rate of MMR at 1 year compared with imatinib (overall OR, 2.22; 95% CI, 1.87 to 2.63). No statistical difference in overall survival at 1 year was found (overall OR, 1.20; 95% CI, 0.63-2.29). Inaccessibility to individual data and time-to-event data and differences in evaluation criteria between studies could have introduced bias. Conclusions and Relevance: Dasatinib, nilotinib, and ponatinib increase vascular occlusive events. New-generation TKIs improve MMR but not the overall survival at 1 year in patients with CML. PMID- 26847664 TI - Stereoselective Synthesis of Functionalized Pyrrolidines by the Diverted N-H Insertion Reaction of Metallocarbenes with beta-Aminoketone Derivatives. AB - A highly stereoselective route to functionalized pyrrolidines by the metal catalyzed diverted N-H insertion of a range of diazocarbonyl compounds with beta aminoketone derivatives is described. A number of catalysts (rhodium(II) carboxylate dimers, copper(I) triflate, and an iron(III) porphyrin) are shown to promote the process under mild conditions to give a wide range of highly substituted proline derivatives. The reaction starts as a metallocarbene N-H insertion but is diverted by an intermolecular aldol reaction. PMID- 26847663 TI - Increasing Coverage of Appropriate Vaccinations: A Community Guide Systematic Economic Review. AB - CONTEXT: Population-level coverage for immunization against many vaccine preventable diseases remains below optimal rates in the U.S. The Community Preventive Services Task Force recently recommended several interventions to increase vaccination coverage based on systematic reviews of the evaluation literature. The present study provides the economic results from those reviews. EVIDENCE ACQUISITION: A systematic review was conducted (search period, January 1980 through February 2012) to identify economic evaluations of 12 interventions recommended by the Task Force. Evidence was drawn from included studies; estimates were constructed for the population reach of each strategy, cost of implementation, and cost per additional vaccinated person because of the intervention. Analyses were conducted in 2014. EVIDENCE SYNTHESIS: Reminder systems, whether for clients or providers, were among the lowest-cost strategies to implement and the most cost effective in terms of additional people vaccinated. Strategies involving home visits and combination strategies in community settings were both costly and less cost effective. Strategies based in settings such as schools and MCOs that reached the target population achieved additional vaccinations in the middle range of cost effectiveness. CONCLUSIONS: The interventions recommended by the Task Force differed in reach, cost, and cost effectiveness. This systematic review presents the economic information for 12 effective strategies to increase vaccination coverage that can guide implementers in their choice of interventions to fit their local needs, available resources, and budget. PMID- 26847665 TI - Laparoscopic Versus Open Distal Pancreatectomy for Pancreatic Adenocarcinoma. AB - BACKGROUND: Laparoscopic distal pancreatectomy (LDP) has been shown to have short term benefits over open distal pancreatectomy (ODP). Its application for pancreatic ductal adenocarcinoma (PDAC) remains controversial. METHODS: From 1995 to 2014, 72 patients underwent distal pancreatectomy for PDAC at a single institution and were included in the study. Postoperative and long-term outcomes of patients undergoing LDP (n = 44) or ODP (n = 28) were compared. RESULTS: LDP was associated with less blood loss (332 vs. 874 mL, p = 0.0012) and lower transfusion rates than ODP (18.2 vs. 50 %, p = 0.0495). Operative time was similar (254 vs. 266 min) for LDP and ODP; five patients (11.4 %) required conversion to ODP. Pancreatic fistulas (13.6 vs. 7.1 %) and major complications (13.6 vs. 25 %), were similar between LDP and ODP, respectively. Length of hospital stay (5.1 vs. 9.4 days, p = 0.0001) and time to initiate adjuvant therapy (69.4 vs. 95.6 days, p = 0.0441) was shorter for LDP than ODP. Tumor characteristics were similar but LDP was associated with more resected lymph nodes than ODP (25.9 vs. 12.7, p = 0.0001). One-, three-, and five-year survival rates were similar between LDP (69, 41, and 41 %, respectively) and ODP (78, 44, and 32 %, respectively). CONCLUSION: LDP is associated with less blood loss and need for blood transfusion, shorter hospital stay, and faster time to initiate adjuvant therapy than ODP for patients with PDAC. Postoperative outcomes and long term survival are similar between the two groups. LDP appears to be safe in the treatment of patients with PDAC. PMID- 26847666 TI - Intracerebral hemorrhage and deep microbleeds associated with cnm-positive Streptococcus mutans; a hospital cohort study. AB - Oral infectious diseases are epidemiologically associated with stroke. We previously showed that oral Streptococcus mutans with the cnm gene encoding a collagen-binding Cnm protein induced intracerebral hemorrhage (ICH) experimentally and was also associated with cerebral microbleeds (CMBs) in our population-based cohort study. We therefore investigated the roles of cnm positive Streptococcus mutans in this single hospital-based, observational study that enrolled 100 acute stroke subjects. The cnm gene in Streptococcus mutans isolated from saliva was screened using PCR techniques and its collagen-binding activities examined. CMBs were evaluated on T2* gradient-recalled echo MRI. One subject withdrew informed consent and 99 subjects (63 males) were analyzed, consisting of 67 subjects with ischemic stroke, 5 with transient ischemic attack, and 27 with ICH. Eleven cases showed Streptococcus mutans strains positive for cnm. The presence of cnm-positive Streptococcus mutans was significantly associated with ICH [OR vs. ischemic stroke, 4.5; 95% CI, 1.17-19.1] and increased number of deep CMBs [median (IQR), 3 (2-9) vs. 0 (0-1), p = 0.0002]. In subjects positive for Streptococcus mutans, collagen binding activity was positively correlated with the number of deep CMBs (R(2) = 0.405; p < 0.0001). These results provide further evidence for the key role of oral health in stroke. PMID- 26847668 TI - Trends in disability and program participation among U.S. veterans. AB - BACKGROUND: Disability is increasingly part of the lives of veterans and more research is needed to understand its impact on veterans' participation in disability benefit programs. OBJECTIVE/HYPOTHESIS: We examine how recent trends in receipt of service-connected disability compensation from the Department of Veterans Affairs (VA) compare to trends in self-reported disability and participation in Social Security Disability Insurance (DI) and Supplemental Security Income (SSI) among veterans. METHODS: We use 2002-2013 data from the Current Population Survey to describe trends in receipt of VA disability compensation and to compare between trends in self-reported disability and DI/SSI participation for veterans versus nonveterans. RESULTS: The percentage of veterans reporting they receive VA disability compensation increased substantially from 2002 to 2013 and was especially notable among younger (ages 18 39) and older (ages 50-64) veterans. From 2009 to 2013, self-reported disability increased among the younger and older veterans but not among middle-age veterans and nonveterans, and self-reported cognitive disability increased substantially among young veterans. DI/SSI participation among older veterans increased more than for nonveterans over the period examined. CONCLUSIONS: Effective policies are needed to incentivize work among young veterans and to help them obtain both the skills they need to succeed in the labor force and the supports (such as psychiatric health services) they need to do so. Older veterans are facing increasing challenges in the labor market, and further research is needed to determine whether these challenges are primarily related to health, a growing skills gap, or poorly-aligned incentives. PMID- 26847667 TI - Determining the Pathogenic Potential of Non-sporulating Molds Isolated from Cutaneous Specimens. AB - Although non-sporulating molds (NSM) are frequently isolated from patients and have been recognized as agents of pulmonary disease, their clinical significance in cutaneous specimens is relatively unknown. Therefore, this study aimed to identify NSM and to determine the keratinolytic activity of isolates from cutaneous sites. NSM isolates from clinical specimens such as skin, nail, and body fluids were identified based on their ribosomal DNA sequences. Of 17 NSM isolates (7 Ascomycota, 10 Basidiomycota), eleven were identified to species level while five were identified to the genus level. These include Schizophyllum commune, a known human pathogen, Phoma multirostrata, a plant pathogen, and Perenniporia tephropora, a saprophyte. To determine fungal pathogenicity, keratinolytic activity, a major virulence factor, was evaluated ex vivo using human nail samples by measuring dye release from keratin azure, for NSM along with pathogens (Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis and Fusarium spp.) and nonpathogenic (endophyte) fungi for comparison. This study showed that pathogenic fungi had the highest keratinolytic activity (7.13 +/- 0.552 keratinase units) while the nonpathogenic endophytes had the lowest activity (2.37 +/- 0.262 keratinase units). Keratinolytic activity of two Ascomycota NSM (Guignardia mangiferae and Hypoxylon sp.) and one Basidiomycota NSM (Fomitopsis cf. meliae) was equivalent to that of pathogenic fungi, while Xylaria feejeensis showed significantly higher activity (p < 0.05) than nonpathogenic endophytes. These results indicate that the pathogenic ability of NSM is species dependent; clinical isolates, especially more frequently isolated species, may be involved in disease etiology. PMID- 26847669 TI - Pregnancy among women with physical disabilities: Unmet needs and recommendations on navigating pregnancy. AB - BACKGROUND: Despite concerns raised in the literature on the adverse pregnancy outcomes of women with physical disabilities, there is little information about unmet needs of women with physical disabilities during pregnancy and childbirth. OBJECTIVE: This article provides an in-depth examination of unmet health care needs during and around the time of pregnancy among a sample of women with physical disabilities. It also offers recommendations to other women with physical disabilities who are considering pregnancy. METHODS: Twenty-five phone interviews were conducted with women with physical disabilities from across the United States who had a baby in the past ten years. Individual semi-structured qualitative interviews lasting about 2 h were conducted. Interviews were audio recorded, transcribed, and analyzed using an iterative, interpretive process. RESULTS: Women reported a wide range of disabling conditions. Analysis revealed three broad themes related to unmet needs during pregnancy among women with physical disabilities. They included (1) clinician knowledge and attitudes, (2) physical accessibility of health care facilities and equipment, (3) need for information related to pregnancy and postpartum supports. The women also provided recommendations to other women with disabilities who are currently pregnant or thinking of becoming pregnant. Recommendations related to finding a clinician one trusts, seeking peer support, self-advocating, and preparing oneself for the baby. CONCLUSIONS: This study sheds light on the unmet needs and barriers to care of women with mobility disabilities during pregnancy and childbirth. The study findings highlight the need for policy and practice recommendations for perinatal care of women with mobility disabilities. PMID- 26847671 TI - On Gelsemium and Complementary and Alternative Medicine (CAM) in Anxiety and Experimental Neurology. AB - A recent discussion expanded the debate about the experimental research on Gelsemium in anxiety. Herbal medicine is widely used in anxiety and mood disorders, often with contradictory evidence, although some authors are yet prompted to promote their full introduction in pharmacology as a promising therapy. Complementary and alternative medicine (CAM) in anxiety is particularly appreciated by individual healthcare, but deserves further investigation, as many critical issues have been recently raised. Comments about the ability of negligible doses of Gelsemium hydroalcoholic extracts to affect gene expression were recently reported. PMID- 26847672 TI - Latent Class Analysis to Classify Patients with Transthyretin Amyloidosis by Signs and Symptoms. AB - INTRODUCTION: The aim of this study was to develop an empirical approach to classifying patients with transthyretin amyloidosis (ATTR) based on clinical signs and symptoms. METHODS: Data from 971 symptomatic subjects enrolled in the Transthyretin Amyloidosis Outcomes Survey were analyzed using a latent class analysis approach. Differences in health status measures for the latent classes were examined. RESULTS: A four-class latent class solution was the best fit for the data. The latent classes were characterized by the predominant symptoms as severe neuropathy/severe autonomic, moderate to severe neuropathy/low to moderate autonomic involvement, severe cardiac, and moderate to severe neuropathy. Incorporating disease duration improved the model fit. It was found that measures of health status varied by latent class in interpretable patterns. CONCLUSION: This latent class analysis approach offered promise in categorizing patients with ATTR across the spectrum of disease. The four-class latent class solution included disease duration and enabled better detection of heterogeneity within and across genotypes than previous approaches, which have tended to classify patients a priori into neuropathic, cardiac, and mixed groups. Although this study utilized a cross-sectional approach to disease duration, future work could include the application of longitudinal latent class analyses. FUNDING: Pfizer Inc., New York, NY, USA. PMID- 26847670 TI - Gene targeting, genome editing: from Dolly to editors. AB - One of the most powerful strategies to investigate biology we have as scientists, is the ability to transfer genetic material in a controlled and deliberate manner between organisms. When applied to livestock, applications worthy of commercial venture can be devised. Although initial methods used to generate transgenic livestock resulted in random transgene insertion, the development of SCNT technology enabled homologous recombination gene targeting strategies to be used in livestock. Much has been accomplished using this approach. However, now we have the ability to change a specific base in the genome without leaving any other DNA mark, with no need for a transgene. With the advent of the genome editors this is now possible and like other significant technological leaps, the result is an even greater diversity of possible applications. Indeed, in merely 5 years, these 'molecular scissors' have enabled the production of more than 300 differently edited pigs, cattle, sheep and goats. The advent of genome editors has brought genetic engineering of livestock to a position where industry, the public and politicians are all eager to see real use of genetically engineered livestock to address societal needs. Since the first transgenic livestock reported just over three decades ago the field of livestock biotechnology has come a long way-but the most exciting period is just starting. PMID- 26847673 TI - Cost-Utility Analysis of Magnetic Resonance Imaging Management of Patients with Acute Ischemic Stroke in a Spanish Hospital. AB - INTRODUCTION: Stroke has a high rate of long-term disability and mortality and therefore has a significant economic impact. The objective of this study was to determine from a social perspective, the cost-utility of magnetic resonance imaging (MRI) compared to computed tomography (CT) as the first imaging test in acute ischemic stroke (AIS). METHODS: A cost-utility analysis of MRI compared to CT as the first imaging test in AIS was performed. Economic evaluation data were obtained from a prospective study of patients with AIS <=12 h from onset in one Spanish hospital. The measure of effectiveness was quality-adjusted life-years (QALYs) calculated from utilities of the modified Rankin Scale. Both hospital and post-discharge expenses were included in the costs. The incremental cost effectiveness ratio (ICER) was calculated and sensitivity analysis was carried out. The costs were expressed in Euros at the 2004 exchange rate. RESULTS: A total of 130 patients were analyzed. The first imaging test was CT in 87 patients and MRI in 43 patients. Baseline variables were similar in the two groups. The mean direct cost was ?5830.63 for the CT group and ?5692.95 for the MRI group (P = not significant). The ICER was ?11,868.97/QALY. The results were sensitive when the indirect costs were included in the analysis. CONCLUSION: Total direct costs and QALYs were lower in the MRI group; however, this difference was not statistically significant. MRI was shown to be a cost-effective strategy for the first imaging test in AIS in 22% of the iterations according to the efficiency threshold in Spain. PMID- 26847674 TI - Concurrent Use of Benzodiazepines and Antidepressants and the Risk of Motor Vehicle Accident in Older Drivers: A Nested Case-Control Study. AB - INTRODUCTION: Aging of the population results in an increase in senior drivers. Elderly are frequently treated with benzodiazepines and antidepressants. The objective of this study was to determine whether the concurrent use of benzodiazepines and antidepressants is associated with motor vehicle accidents (MVAs) in the elderly. METHODS: This was a nested case-control study within a cohort of drivers aged 67-84 years between 1990 and 2000, identified from the Societe de l'Assurance Automobile du Quebec and the Regie de l'Assurance Maladie du Quebec databases. First cases of MVAs during follow-up were matched with up to ten controls from the cohort. Odds ratios (ORs) for the association between MVA and the use of benzodiazepines and antidepressants were estimated using conditional logistic regression. RESULTS: The cohort included 373,818 drivers, with 74,503 MVA cases matched with 744,663 controls. The risk of MVA was higher in current users of long-acting benzodiazepines [OR 1.23; 95% confidence interval (CI) 1.16-1.29] than in current users of short-acting benzodiazepines (OR 1.05; 95% CI 1.02-1.08). The risk of MVA was increased in current users of selective serotonin reuptake inhibitors (SSRIs; OR 1.13; 95% CI 1.04-1.22), while it was not in current users of tricyclic antidepressants (TCAs; OR 1.04; 95% CI 0.96 1.14). The highest ORs of MVA were observed in long-acting benzodiazepines users concurrently using SSRIs (OR 1.37; 95% CI 1.07-1.77, P value for interaction = 0.964) or TCAs (OR 1.54; 95% CI 1.21-1.95, P value for interaction = 0.077). CONCLUSION: Use of long-acting benzodiazepines is associated with an increased risk of MVA in the elderly, particularly in those concurrently using SSRIs or TCAs. PMID- 26847675 TI - Peculiar Cytological Cerebrospinal Fluid Pattern in a Case of Encephalomyelitis During Anti-Tumor Necrosis Factor-alpha Therapy. AB - INTRODUCTION: Tumor necrosis factor-alpha (TNF-alpha) blocking agents may be associated with neurological adverse events, including demyelinating syndromes, that can be difficult to differentiate from multiple sclerosis (MS) and clinically isolated syndrome (CIS) as neither the clinical nor laboratory distinctive features have been reported. Usually clinicians mainly examine the diagnostic value of immunoglobulin G oligoclonal bands underestimating the value of other cerebrospinal fluid (CSF) parameters (such as CSF cytology). CASE REPORT: We present a case of a patient who acutely developed mild pyramidal and sensory impairment of lower limbs and urinary hesitancy during treatment with adalimumab, a monoclonal antibody to TNF-alpha, for psoriatic arthritis. Magnetic resonance imaging demonstrated a widespread area of hyperintense signal extending from C5 to D8 level in T2-weighted images. Two consecutive CSF examinations showed an intense activation of monocyte/macrophage lineage (88% and 90%, respectively) with some giant and binucleated cells that notably decreased five months after TNF-alpha blocker cessation. We compared the results of CSF examinations of our patient with CSF results of 20 patients with MS and 20 patients with CIS that demonstrated activation of both lymphocytic and monocytic lineage (MS: 48% and 52%, respectively, CIS: 54.5% and 43.5%, respectively) that were very different from the findings in adalimumab-related encephalomyelitis in acute phase (11% and 89%, respectively). CSF cytology in two patients with neuromyelitis optica during the relapse (n = 3) showed minor monocyte/macrophage activation (9%) and an increased number of granulocytes (77%). CONCLUSION: Prominent activation of monocyte/macrophage lineage with some binucleated giant cells in CSF could be induced by anti-TNF-alpha treatment. The peculiar CSF pattern, never found in MS, CIS, and NMO, can help in differential diagnosis and stresses the importance of careful CSF cytology evaluation in the course of demyelinating diseases. PMID- 26847676 TI - Correction: Enantiopure titanocene complexes--direct evidence for paraptosis in cancer cells. AB - Correction for 'Enantiopure titanocene complexes--direct evidence for paraptosis in cancer cells' by Melchior Cini et al., Metallomics, 2016, DOI: 10.1039/c5mt00297d. PMID- 26847677 TI - Effects of cerium oxide supplementation to laying hen diets on performance, egg quality, some antioxidant enzymes in serum and lipid oxidation in egg yolk. AB - This study was conducted to determine the effects of dietary cerium oxide levels (0, 100, 200, 300 or 400 mg/kg) on the laying performance, egg quality, some blood serum parameters and egg lipid peroxidation of laying hen. In total, one hundred and twenty 22-week-old brown Lohman LSL laying hens were randomly assigned to five groups equally (n = 24). Each treatment was replicated six times. Dietary supplementation of cerium oxide had no significant effect on feed intake and egg weight. The addition of cerium oxide to the laying hens' feed improved feed conversion ratio and increased (p < 0.05) egg production. Quality criteria of egg for except shell breaking strength were not affected by supplementing cerium oxide. In particular, supplementation of 200 and 300 mg/kg cerium oxide to the laying hens feed led to a significant (p < 0. 01) increase in egg shell breaking strength. Calcium and phosphorus concentration of serum increased significantly (p < 0.05) with supplementation of 100 mg/kg cerium oxide to laying hen diets. It was also observed that serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentration decreased significantly with supplementation of cerium oxide in diets. Inclusion of cerium oxide resulted in a significant reduction in thiobarbituric acid reactive substance (TBARS) values in egg yolk in this study. It can be concluded that the addition of cerium oxide had positive effects on egg production, feed conversion ratio and egg shelf life. Based on the results of this study, it could be advised to supplement laying hens feed with cerium oxide as feed additives. PMID- 26847679 TI - Tumor Infiltrative Pattern Predicts Sites of Recurrence After Curative Gastrectomy for Stages 2 and 3 Gastric Cancer. AB - BACKGROUND: In East Asia, the tumor infiltrative pattern (INF) has been routinely evaluated by hematoxylin and eosin-stained sections as a pathologic characteristic of surgically resected specimens. METHODS: The infiltrative pattern of gastric cancer (GC) has been histopathologically classified as INFa (expansive growth), INFb (intermediate type) and INFc (infiltrative growth) according to the Japanese Classification of Gastric Carcinoma. The prognostic value and characteristics of the disease recurrence pattern for each INF type were assessed in 785 patients with various stages of GC and also in 243 patients with stages 2 and 3 GC. RESULTS: Comparison of the overall survival experienced by patients independently of stage showed that INF was significantly associated with prognosis. Specifically, peritoneal metastasis was present in 91 % of stage 4 patients in the INFc group, whereas hepatic metastasis was present in 39 % of stage 4 patients in the INFa and INFb group. After curative gastrectomy of patients with stages 2 or 3 GC, INF was not significantly associated with survival. The prevalence of peritoneal recurrence was significantly higher in the INFc group than in the INFa and INFb group, whereas the prevalence of hepatic recurrence was significantly higher in the INFa and INFb group than in the INFc group. Multivariate analysis identified INFc as an independent risk factor for peritoneal recurrence after curative gastrectomy. The association of the INF type with the incidence of peritoneal recurrence was observed with all disease stages regardless whether the patient was given adjuvant chemotherapy or not. CONCLUSIONS: Evaluation of the INF type shows promise for its role as a predictor of postoperative recurrence sites in patients with GC. PMID- 26847678 TI - Analysis of Clinical and Molecular Factors Impacting Oncologic Outcomes in Undifferentiated Pleomorphic Sarcoma. AB - BACKGROUND: Undifferentiated pleomorphic sarcomas (UPS) present a diagnostic and therapeutic challenge. Identification of prognostic molecular markers is required for the discovery of novel treatment approaches. The purpose of this study was to correlate clinicopathologic variables, expression of tyrosine kinase receptors, and markers of cell cycle progression and survival with oncologic outcomes. METHODS: A tissue microarray containing 208 primary UPS samples was analyzed by immunohistochemistry for protein markers and in situ hybridization for microRNA. Staining results were correlated with clinicopathologic features and oncologic outcomes. Univariate and multivariate analyses were conducted to assess associations between expression of protein markers, mi-RNA, and outcome. RESULTS: At a median follow-up of 3.9 years (9 years for survivors), 5-year disease specific survival (DSS) was 63 %. Clinical variables associated with improved DSS included age <61 years, tumor size <10 cm, margin-negative resection, and sporadic-tumor status. At the protein level, loss of cyclin D1 (p = 0.06), pEGFR (p = 0.023), pIGF-1R (p = 0.022), and PTEN (p < 0.001) and overexpression of AXL (p = 0.015) were associated with reduced DSS on univariate analysis. Ki67, PCNA, and pEGFR were more highly expressed in sporadic UPS than radiation-associated (RA-UPS), whereas RA-UPS samples expressed higher levels of both phosphorylated and total IGF-1R. DISCUSSION: Loss of cyclin D1, overexpression of AXL, and loss of PTEN are associated with poor cancer-specific outcomes and warrant further investigation in UPS. The differences in protein expression in sporadic versus RA UPS may indicate that the activated molecular signaling nodes may be different for each specific histology and also could explain the aggressive phenotype seen in RA-UPS compared with the sporadic lesions. PMID- 26847680 TI - Pilot Study of a New Nonradioactive Surgical Guidance Technology for Locating Nonpalpable Breast Lesions. AB - BACKGROUND: The current technique for locating nonpalpable breast lesions is wire localization (WL). Radioactive seed localization and intraoperative ultrasound were developed to improve difficulties with WL. The SAVI SCOUT surgical guidance system was developed to improve these methods. The SCOUT system is a non radioactive, FDA-cleared medical device that uses electromagnetic wave technology to provide real-time guidance during excisional breast procedures. METHODS: Consenting patients underwent localization and excision using an implantable electromagnetic wave reflective device (reflector) and a detector handpiece with a console. Using image guidance, the reflector was placed up to 7 days before the surgical procedure. The primary end points of the study were successful reflector placement, localization, and retrieval. The secondary end points were percentage of clear margins, reexcision rates, days of placement before excision, and physician comparison with WL. RESULTS: This study analyzed 50 patients. The reflectors were placed under mammographic guidance (n = 18, 36 %) or ultrasound guidance (n = 32, 64 %). Of the 50 patients, 10 (20 %) underwent excisional biopsy and 40 (80 %) had a lumpectomy. The lesion and reflector were successfully removed in all 50 patients, and no adverse events occurred. Of the 41 patients who had in situ and/or invasive carcinoma identified, 38 (93 %) had clear margins and 3 (7 %) were recommended for reexcision. CONCLUSIONS: These data suggest that the SCOUT system is safe and effective for guiding the excision of nonpalpable breast lesions and a viable alternative to standard localization options. A larger prospective, multi-institution trial of SCOUT currently is underway to validate these findings. PMID- 26847681 TI - Antibody-Mediated Blockade of Phosphatidylserine Enhances the Antitumor Effect of Sorafenib in Hepatocellular Carcinomas Xenografts. AB - BACKGROUND: Currently, the only FDA-approved systemic therapy for hepatocellular carcinoma (HCC) is the multi-receptor tyrosine kinase inhibitor, sorafenib, which provides only modest clinical benefit. We recently showed that treatment with a phosphatidylserine (PS) targeting agent suppresses tumor growth by targeting tumor vasculature and reactivating antitumor immunity. METHODS: We tested the hypothesis that sorafenib increases PS exposure on tumor vasculature, thereby enhancing the antitumor efficacy of PS targeting. We evaluated the efficacy of combining a PS targeting agent (2aG4) with sorafenib in murine xenograft models of human HCC. RESULTS: Our results demonstrate that combination of 2aG4 and sorafenib had a superior therapeutic effect over single agent therapy. Mechanistic studies showed that sorafenib significantly increased PS exposure on tumor vasculature; the percentage of PS-positive vessels increased from 19 to 52, 23 to 68, and 30 to 55 % in PLC/PRF/5, C3A, and Huh7 tumors, respectively. Combination therapy significantly decreased tumor microvessel density and the level of M2 macrophages, while increasing the apoptotic index of tumor endothelial cells and the frequency of M1 macrophages. Furthermore, we report the findings of a Phase I clinical study of bavituximab, a chimeric version of 2aG4, combined with sorafenib in HCC patients. The Phase I results demonstrate the appropriate dose of bavituximab to be given with sorafenib in future clinical trials. CONCLUSIONS: Overall, these results strongly support the combination of bavituximab with sorafenib as a promising systemic therapeutic strategy for the treatment for advanced HCC patients. PMID- 26847682 TI - Adjuvant Trametinib Delays the Outgrowth of Occult Pancreatic Cancer in a Mouse Model of Patient-Derived Liver Metastasis. AB - PURPOSE: Most patients with pancreatic ductal adenocarcinoma (PDAC) die within 5 years following resection plus adjuvant gemcitabine (Gem) from outgrowth of occult metastases. We hypothesized that inhibition of the KRAS pathway with the MEK inhibitor trametinib would inhibit the outgrowth of occult liver metastases in a preclinical model. METHODS: Liver metastases harvested from two patients with PDAC (Tumors 608, 366) were implanted orthotopically in mice. Tumor cell lines were derived and transduced with lentiviruses encoding luciferase and injected into spleens of mice generating microscopic liver metastases. Growth kinetics of liver metastases were measured with bioluminescent imaging and time to-progression (TTP), progression-free survival (PFS), and overall survival (OS) were determined. RESULTS: Trametinib (0.3 mg/kg BID) significantly prolonged OS versus control (Tumor 608: 114 vs. 43 days, p < 0.001; Tumor 366: not reached vs. 167 days, p = 0.0488). In vivo target validation demonstrated trametinib significantly reduced phosphorylated-ERK and expression of the ERK-responsive gene DUSP6. In a randomized, preclinical trial, mice were randomized to: (1) control, (2) adjuvant Gem (100 mg/kg IP, Q3 days) * 7 days followed by surveillance, or (3) adjuvant Gem followed by trametinib. Sequential Gem trametinib significantly decreased metastatic cell outgrowth and increased TTP and PFS. CONCLUSIONS: Treatment of mice bearing micrometastases with trametinib significantly delayed tumor outgrowth by effectively inhibiting KRAS-MEK-ERK signaling. In a randomized, preclinical, murine trial adjuvant sequential Gem followed by trametinib inhibited occult metastatic cell outgrowth in the liver and increased PFS versus adjuvant Gem alone. An adjuvant trial of sequential Gem trametinib is being planned in patients with resected PDAC. PMID- 26847683 TI - A Population-Based Cost Analysis of Thoracoscopic Versus Open Lobectomy in Primary Lung Cancer. AB - BACKGROUND: Thoracoscopic lobectomy for primary lung cancer has become increasingly popular worldwide due to several advantages over open lobectomy including reduced pain, reduced length of hospital stay, and comparable oncologic outcomes. The costs of thoracoscopic versus conventional open lobectomy have been compared in several studies with variable results. We compared the costs of thoracoscopic versus open lobectomy in lung cancer patients in Taiwan. METHODS: Patients who underwent lobectomy for primary lung cancer from the Taiwan National Health Insurance Research Database (NHIRD) between 2004 and 2010 were identified. Patient characteristics, operative data, and costs for each part of the hospitalization for surgery and 30 days of care after discharge were analyzed. RESULTS: A total of 5366 patients with complete clinical data who underwent either conventional open lobectomy (n = 3166, 59 %) or thoracoscopic lobectomy (n = 2200, 41 %) for primary lung cancer were identified from the database. Compared with open lobectomy, thoracoscopic lobectomy was associated with younger age, less comorbidity, shorter anesthesia times, and reduced lengths of hospital stay. Total hospital costs, operative costs, and other costs were significantly higher in the thoracoscopic group. The 30-day after discharge costs were significantly lower in the thoracoscopic group. CONCLUSIONS: Thoracoscopic lobectomy for primary lung cancer in Taiwan was associated with higher total hospital costs but lower 30 days after discharge costs than open lobectomy. These differences may have resulted from higher operative and instrument costs in the thoracoscopic group. PMID- 26847684 TI - Effect of EGFR and p-AKT Overexpression on Chromosomal Instability in Gastric Cancer. AB - BACKGROUND: Molecular profiling in gastric cancer (GC) is important for diagnosis and treatment. In this study, we investigated signal transduction pathways that might induce chromosomal instability in GC. METHODS: Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and p-AKT expression were analyzed using immunohistochemistry, and chromosomal instability was assessed by DNA aneuploidy using laser scanning cytometry, in a total of 202 GC cases. RESULTS: The rate of EGFR expression and p-AKT expression was 70.3 and 34.2 %, respectively, in GC patients. In total, 57.5 % of GC patients exhibited DNA aneuploidy, and p-AKT positively correlated with EGFR and HER2 (p = 0.0127 and p = 0.00031, respectively). Patients with EGFR overexpressing GC showed shorter disease-specific survival than the other cases (hazard ratio 2.00, 95 % confidence interval 1.19-3.53; p = 0.0104). Moreover, EGFR and p-AKT expression was significantly correlated with DNA aneuploidy (p = 0.0002 and p = 0.0302, respectively). CONCLUSIONS: Our data showed that both EGFR and p-AKT overexpression were clearly associated with DNA aneuploidy. Aneuploidy could be a useful marker for therapies that target EGFR. PMID- 26847686 TI - Preoperative axillary lymph node staging by ultrasound-guided cytology using a four-level sonographic score. AB - BACKGROUND: The staging of axillary lymph nodes is critical to the management and prognosis of breast cancer, the most frequent cancer in females. Neoadjuvant therapy and lymph node dissection are recommended when malignant cells invade the lymph nodes. Therefore the pre-operative examination of these lymph nodes is crucial to treatment. METHODS: In this study, we examined the effectiveness of cytology through ultrasound-guided fine needle aspiration (USG-FNA) and ultrasound (US) imaging using an established classification system in correctly identifying lymph node status compared to the final histological results after surgery. RESULTS: Cytology by USG-FNA and US classification were found to be promising methods of axillary lymph node staging. CONCLUSIONS: US and CB offer minimally invasive techniques to pre-operatively examine these lymph nodes in patients with primary breast cancer. PMID- 26847685 TI - Automatic screening of cervical cells using block image processing. AB - BACKGROUND: Cervical cancer is the second leading cause of female-specific cancer related deaths after breast cancer, especially in developing countries. However, the incidence of the disease may be significantly decreased if the patient is diagnosed in the pre-cancerous lesion stage or earlier. In recent years, computer based algorithms are widely used in cervical cancer screening. Most of the proposed algorithms follow the procedure of segmentation, feature extraction, and then classification. Nevertheless, few of the existing segmentation methods are as flexible and robust as the human visual system, and the complexity of the algorithms makes it difficult for clinical application. METHODS: In this study, a computer-assisted analytical approach is proposed to identify the existence of suspicious cells in a whole slide cervical cell image (WSCCI). The main difference between our method and the conventional algorithm is that the image is divided into blocks with certain size instead of segmented cells, which can greatly reduce the computational complexity. Via data analysis, some texture and color histogram features show significant differences between blocks with and without suspicious cells. Therefore these features can be used as the input of the support vector machine classifier. 1100 non-background blocks (110 suspicious blocks) are trained to build a model, while 1040 blocks (491 non-background blocks) from 12 other WSCCIs are tested to verify the feasibility of the algorithm. RESULTS: The experimental results show that the accuracy of our method is about 98.98 %. More importantly, the sensitivity, which is more fatal in cancer screening, is 95.0 % according to the images tested in the study, while the specificity is 99.33 %. CONCLUSION: The analysis of the algorithm is based on block images, which is different from conventional methods. Although some analysis work should be done in advance, the later processing speed will be greatly enhanced with the establishment of the model. Furthermore, since the algorithm is based on the actual WSCCI, the method will be of directive significance for clinical screening. PMID- 26847687 TI - Monoacylglycerol lipase inhibitor JZL184 regulates apoptosis and migration of colorectal cancer cells. AB - Monoacylglycerol lipase (MAGL) is involved in the degradation of triacylglycerol. Previous studies have demonstrated that MAGL regulates tumor growth and metastasis via fatty acid networks, and is associated with colorectal cancer. JZL184 is a MAGL inhibitor, which in the present study was administered to colorectal cancer cell lines, resulting in decreased tumor proliferation, increased apoptosis and increased tumor cell sensitivity to 5-fluorouracil. B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) are key proteins in apoptosis. The expression levels of Bcl-2/Bax were determined in colorectal cancer cell lines following JZL184 administration, and it was observed that the mRNA and protein expression levels of Bcl-2 were decreased, whereas the expression levels of Bax were increased. These results indicated that JZL184 may induce tumor cell apoptosis by regulating the expression of Bcl-2 and Bax. Epithelial-mesenchymal transition (EMT) is closely associated with metastasis. Administration of JZL184 in various malignant colorectal cancer cell lines suppressed migration and altered the expression of EMT markers; E-cadherin was increased, whereas the expression levels of vimentin and zinc finger protein SNAI1 were decreased. These results suggested that JZL184 was able to regulate the EMT process, in order to control the migration of colorectal cancer cells, particularly in tumors with a stronger metastatic capability. Therefore, in colorectal cancer, MAGL may be considered a potential therapeutic target and JZL184 may be a possible therapeutic agent. PMID- 26847688 TI - MuA-mediated in vitro cloning of circular DNA: transpositional autointegration and the effect of MuB. AB - Transposons provide useful tools for genetics and genomics studies, as they can be modified easily for a variety of purposes. In this study, a strategy to clone circular DNA was developed on the basis of an efficient Mu in vitro transposition reaction catalyzed by MuA transposase. The transposon used contains a selectable marker as well as an origin of replication, and in vitro integration of the transposon into circular DNA generates a plasmid that can replicate in E. coli. We show that the substrate stoichiometry plays an important role in the profile of intermolecular versus intramolecular transposition reaction products. Increasing the relative amount of target DNA reduced the frequency of intramolecular products that are non-productive with regard to the developed cloning application. Such autointegration was also reduced in the reactions containing phage Mu-encoded MuB, indicating that this protein can be used for cloning in combination with MuA, and it is particularly useful with a limited amount of target DNA. The developed strategy can now be utilized to clone DNA circles regardless of their origin as long as their size is not prohibitive for transformation. PMID- 26847689 TI - The paradoxical psychological effects of lysergic acid diethylamide (LSD). AB - BACKGROUND: Lysergic acid diethylamide (LSD) is a potent serotonergic hallucinogen or psychedelic that modulates consciousness in a marked and novel way. This study sought to examine the acute and mid-term psychological effects of LSD in a controlled study. METHOD: A total of 20 healthy volunteers participated in this within-subjects study. Participants received LSD (75 ug, intravenously) on one occasion and placebo (saline, intravenously) on another, in a balanced order, with at least 2 weeks separating sessions. Acute subjective effects were measured using the Altered States of Consciousness questionnaire and the Psychotomimetic States Inventory (PSI). A measure of optimism (the Revised Life Orientation Test), the Revised NEO Personality Inventory, and the Peter's Delusions Inventory were issued at baseline and 2 weeks after each session. RESULTS: LSD produced robust psychological effects; including heightened mood but also high scores on the PSI, an index of psychosis-like symptoms. Increased optimism and trait openness were observed 2 weeks after LSD (and not placebo) and there were no changes in delusional thinking. CONCLUSIONS: The present findings reinforce the view that psychedelics elicit psychosis-like symptoms acutely yet improve psychological wellbeing in the mid to long term. It is proposed that acute alterations in mood are secondary to a more fundamental modulation in the quality of cognition, and that increased cognitive flexibility subsequent to serotonin 2A receptor (5-HT2AR) stimulation promotes emotional lability during intoxication and leaves a residue of 'loosened cognition' in the mid to long term that is conducive to improved psychological wellbeing. PMID- 26847690 TI - Selenium, Zinc, Copper, and Total Antioxidant Status in the Serum of Patients with Chronic Tonsillitis. AB - Antioxidants can play a significant role in chronic inflammatory process. The aim of this study was to evaluate the content of selenium (Se), zinc (Zn), copper (Cu), and total antioxidant status (TAS) of patients with chronic tonsillitis (CT). The study group consisted of 84 patients with CT from 18 to 62 years old and the control group of 67 healthy people aged 19-65 years. Se, Zn, and Cu concentration in serum samples were determined by atomic absorption spectrometry. Serum TAS was measured spectrophotometrically, using the test by Randox Laboratories-Us Ltd. The mean content of Se and Zn in the serum of patients with CT (61.122 +/- 12.73 MUg/L, 0.887 +/- 0.26 mg/L, respectively) was lower compared to the control group (77.969 +/- 12.73 MUg/L, 0.993 +/- 0.32 mg/L, respectively). The mean serum concentration of Cu in patients with CT (1.219 +/- 0.35 mg/L) was higher compared to its serum concentration in healthy people (1.033 +/- 0.37 mg/L). Serum TAS of patients with CT (1.171 +/- 0.33 mmol/L) was lower in comparison with healthy volunteers (1.333 +/- 0.42 mmol/L). The serum concentration of Se, Zn, and TAS in patients with CT was lower, whereas the concentration of Cu was higher compared to healthy volunteers. Smoking has an influence on reducing the concentration of Se and TAS of patients with CT. PMID- 26847691 TI - Synthesis of Gold Nanoparticles with Buffer-Dependent Variations of Size and Morphology in Biological Buffers. AB - The demand for biologically compatible and stable noble metal nanoparticles (NPs) has increased in recent years due to their inert nature and unique optical properties. In this article, we present 11 different synthetic methods for obtaining gold nanoparticles (Au NPs) through the use of common biological buffers. The results demonstrate that the sizes, shapes, and monodispersity of the NPs could be varied depending on the type of buffer used, as these buffers acted as both a reducing agent and a stabilizer in each synthesis. Theoretical simulations and electrochemical experiments were performed to understand the buffer-dependent variations of size and morphology exhibited by these Au NPs, which revealed that surface interactions and the electrostatic energy on the (111) surface of Au were the determining factors. The long-term stability of the synthesized NPs in buffer solution was also investigated. Most NPs synthesized using buffers showed a uniquely wide range of pH stability and excellent cell viability without the need for further modifications. PMID- 26847693 TI - Characteristic of the Nanoparticles Formed on the Carbon Steel Surface Contacting with 3d-Metal Water Salt Solutions in the Open-Air System. AB - The contact of a steel electrode with water dispersion medium in an open-air system leads to the development of various polymorphic iron oxides and oxyhydroxides on the steel surface. Whereas the usage of distilled water causes the obtaining of Fe(II)-Fe(III) layered double hydroxides (green rust) as a primary mineral phase, but in the presence of inorganic 3d-metal water salt solutions, mixed layered double hydroxides (LDHs) together with non stoichiometric spinel ferrite nanoparticles are formed on the steel surface. Mixed LDHs keep stability against further oxidation and complicate the obtaining of spinel ferrite nanoparticles. Thermal treatment of mixed LDHs among other mineral phases formed via the rotation-corrosion dispergation process at certain temperatures permits to obtain homogenous nanoparticles of spinel ferrites as well as maghemite or hematite doped by 3d-metal cations. PMID- 26847692 TI - Effect of Terminal Groups of Dendrimers in the Complexation with Antisense Oligonucleotides and Cell Uptake. AB - Poly(amidoamine) dendrimers are the most recognized class of dendrimer. Amino terminated (PAMAM-NH2) and hydroxyl-terminated (PAMAM-OH) dendrimers of generation 4 are widely used, since they are commercially available. Both have different properties, mainly based on their different overall charges at physiological pH. Currently, an important function of dendrimers as carriers of short single-stranded DNA has been applied. These molecules, known as antisense oligonucleotides (asODNs), are able to inhibit the expression of a target mRNA. Whereas PAMAM-NH2 dendrimers have shown to be able to transfect plasmid DNA, PAMAM-OH dendrimers have not shown the same successful results. However, little is known about their interaction with shorter and more flexible molecules such as asODNs. Due to several initiatives, the use of these neutral dendrimers as a scaffold to introduce other functional groups has been proposed. Because of its low cytotoxicity, it is relevant to understand the molecular phenomena involving these types of dendrimers. In this work, we studied the behavior of an antisense oligonucleotide in presence of both types of dendrimers using molecular dynamics simulations, in order to elucidate if they are able to form stable complexes. In this manner, we demonstrated at atomic level that PAMAM-NH2, unlike PAMAM-OH, could form a well-compacted complex with asODN, albeit PAMAM-OH can also establish stable interactions with the oligonucleotide. The biological activity of asODN in complex with PAMAM-NH2 dendrimer was also shown. Finally, we revealed that in contact with PAMAM-OH, asODN remains outside the cells as TIRF microscopy results showed, due to its poor interaction with this dendrimer and cell membranes. PMID- 26847694 TI - Preparation and Characterization of Silica-Enoxil Nanobiocomposites. AB - Silica-Enoxil nanobiocomposites with 13 %w of Enoxil were prepared either by mechanical mixing of corresponding powders or by sorptive modification of fumed silica powder with aqueous Enoxil solution under fluidized bed conditions. The interaction of fumed silica with Enoxil and the properties of silica-Enoxil composites have been investigated using IR spectroscopy, thermogravimetric analysis, and quantum chemistry methods, as well as by means of water absorption, Enoxil desorption, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) test. It has been shown that the main biomolecules of Enoxil composition interact with silica involving their hydroxyl groups and surface silanol groups. The water absorption of silica-Enoxil nanocomposites was found to be less than that for the individual components. The Enoxil biomolecules are readily and completely desorbed from silica surface into water, and the antioxidant activity of desorbed Enoxil is practically the same as that for the just dissolved one. PMID- 26847695 TI - Silver- and Gold-Ordered Structures on Single-Crystal Silicon Surface After Thermal Deposition. AB - The formation mechanisms of Ag- and Au-ordered structures on single-crystal silicon (Si) (111) and Si (110) surfaces were researched using high-resolution scanning tunneling microscopy method. It was shown that different patterns of self-assembled nanostructures with very precise and regular geometric shapes can be produced by controlling process parameters of thermal metal spraying on the substrate. The surfaces of nanorelieves at each stage of deposition were researched, and the main stages of morphological transformation were fixed.Self ordered hexagonal pyramid-shaped nanostructures were formed at thermal deposition of gold on the Si (111), whereas only monolayer hexagonal formation could be observed on the plane Si (110). Gold monolayer flake nanostructures were obtained under certain technological parameters.Atomically smooth Ag film cannot be obtained on the Si (111) surface by means of thermal spraying at room temperature. The formation of two-dimensional (2D) clusters takes place; heating of these clusters at several hundred degrees Celsius leads to their transformation into atomically smooth covering.The weak interaction between Ag multilayer coatings and substrate was established that allows to clear crystal surface from metal with reproduction of the reconstructed Si (111) 7 * 7 surface by slight warming. The offered method can be used for single-crystal surface protection from destruction. PMID- 26847696 TI - DC bias immune nanocrystalline magnetic cores made of Fe73Nb3Cu1B7Si16 ribbon with induced transverse magnetic anisotropy. AB - The comparative analysis of magnetic properties of cut cores made of nanocrystalline Fe73Nb3Cu1B7Si16 alloy ribbon and cores made of the same ribbon with preliminary tension-induced transverse magnetic anisotropy was carried out. The possibility of improving magnetic properties of cut cores, decreasing loss, and increasing DC bias immunity of reversible magnetic permeability is presented. The influence of induced magnetic anisotropy on DC bias immunity of reversible magnetic permeability was investigated. The advantages and disadvantages of new cores (made of ribbon heated under tensile stress) over cut ones were determined. PMID- 26847697 TI - Fundamental Study on the Fabrication of Inverted Planar Perovskite Solar Cells Using Two-Step Sequential Substrate Vibration-Assisted Spray Coating (2S-SVASC). AB - In this paper, a scalable and fast process is developed and employed for the fabrication of the perovskite light harvesting layer in inverted planar heterojunction solar cell (FTO/PEDOT:PSS/CH3NH3PbI3-x Cl x /PCBM/Al). Perovskite precursor solutions are sprayed onto an ultrasonically vibrating substrate in two sequential steps via a process herein termed as the two-step sequential substrate vibration-assisted spray coating (2S-SVASC). The gentle imposed ultrasonic vibration on the substrate promotes droplet spreading and coalescence, surface wetting, evaporation, mixing of reagents, and uniform growth of perovskite nanocrystals. The role of the substrate temperature, substrate vibration intensity, and the time interval between the two sequential sprays are studied on the roughness, coverage, and crystalline structure of perovskite thin films. We demonstrate that a combination of a long time interval between spraying of precursor solutions (15 min), a high substrate temperature (120 degrees C), and a mild substrate vibration power (5 W) results in a favorable morphology and surface quality. The characteristics and performance of prepared perovskite thin films made via the 2S-SVASC technique are compared with those of the co-sprayed perovskite thin films. The maximum power conversion efficiency of 5.08 % on a 0.3 cm(2) active area is obtained for the device made via the scalable 2S-SVASC technique. PMID- 26847698 TI - Bioinformatics analysis of molecular mechanisms involved in intervertebral disc degeneration induced by TNF-alpha and IL-1beta. AB - The present study aimed to explore the molecular mechanisms associated with intervertebral disc degeneration (IDD) induced by tumor necrosis factor (TNF) alpha and interleukin (IL)-1beta. The microarray dataset no. GSE42611 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between four experimental nucleus pulposus samples and four control nucleus pulposus samples were analyzed. Subsequently, Gene Ontology (GO) and pathway enrichment analyses of DEGs were performed, followed by protein protein interaction (PPI) network construction and prediction of a regulatory network of transcription factor (TFs). Finally, the transcriptional regulatory network was integrated into the PPI network to analyze the network modules. A total of 246 upregulated and 290 downregulated DEGs were identified. The upregulated DEGs were mainly associated with GO terms linked with inflammatory response and apoptotic pathways, while the downregulated DEGs were mainly associated with GO terms linked with cell adhesion and pathways of extracellular matrix - receptor interaction. In the PPI network, IL6, COL1A1, NFKB1 and HIF1A were hub genes, and in addition, NFKB1 and HIF1A were TFs. Pathways of apoptosis and extracellular matrix - receptor interaction may have important roles in IDD progression. IL6, COL1A1 and the TFs NFKB1 and HIF1A may be used as biomarkers for IDD diagnosis and treatment. PMID- 26847699 TI - Enhanceosome transcription factors preferentially dimerize with high mobility group proteins. AB - BACKGROUND: The enhanceosome is an enhancer located upstream of the human interferon beta gene, bound by transcription factor (TF) complex of extremely rigid structure. Within these rigid constraints, even a slight change of distances between transcription factor binding sites (TFBS) results in loss of functionality of the enhanceosome. We hypothesized that smaller subunits of the enhanceosome may entail TF complex formation in other regulatory regions. RESULTS: In order to verify this hypothesis we systematically searched for dimerization preferences of the TFs that have TFBS in the enhanceosome. For this we utilized our recently developed tool, TACO. We performed this computational experiment in a cell-type-specific manner by utilizing cell-type-specific DNase seq data for 105 human cell types. We also used 20 TRANSFAC motifs comprising not only the usual TFs constituting the enhanceosome but also the architectural proteins of High Mobility Group I(Y) (HMG I). A similar experiment used 42 DNase seq data sets for mouse cell types. We found 137 statistically significant dimer predictions in the human genome, and 37 predictions in the mouse genome, that matched the positioning on the enhanceosome with +/-2 bp tolerance. To characterize these predicted TF dimers, we performed functional analysis (Gene Ontology enrichment) for sets of genes which were in the neighbourhood of predicted dimer instances. A notable feature of these instances is that (1) most of them are located in introns of genes, (2) they are enriched in regulatory states, and (3) those instances that are located near transcription start sites are enriched for inclusion in computationally predicted enhancers. We also investigated similarity of dimer predictions between human and mouse. CONCLUSIONS: It follows from our experiments that, except for homodimer formed by IRF proteins, the rest of the dimers were formed exclusively between one of the transcriptional activators (ATF-2/c-Jun and IRF) and a HMG I protein. NF- kappaB did not participate in forming dimers with other proteins. Dimers predicted in mouse were fully contained in those predicted in human, with exactly the same spacing and orientation. Intriguingly, in most of the cases the enhanceosome motifs have 1 bp wider spacing than the corresponding dimers predicted genome wide, which is likely caused by the overall 3D structure constraints of the enhanceosome-bound complex. PMID- 26847700 TI - The effect of fixed appliances on oral malodor from beginning of treatment till 1 year. AB - BACKGROUND: Orthodontic appliances can enhance plaque accumulation, and this can cause gingival inflammation. Halitosis of oral origin is associated with microbial metabolism on the tongue and in the saliva, dental plaque, and the amount of volatile sulfide-containing compounds. This study used a Halimeter to investigate fixed orthodontic therapy-associated increases in the oral malodor over a year. METHODS: Thirteen orthodontic patients with Angle Class I malocclusions receiving fixed orthodontic therapy formed the study group, and 12 dental students without any dental treatment formed the control group. The Halimeter was used to examine oral malodor by detecting volatile sulfur compounds (VSC). Plaque index (PI), gingival index (GI), and probing pocket depth (PPD) were also measured in both groups. The subjects in the study group had one visit before the orthodontic treatment started and seven visits during orthodontic therapy (1, 3, 5, 7, 9, 11, and 13 months after bonding), while the subjects in the control group had three visits, once per subsequent month. RESULTS: Oral malodor was significantly increased in the fixed orthodontic treatment group during treatment (p < .05). Increases were also observed in the PI, GI, and PPD measures (p < .05). The results of the control group were stable (p > .05). CONCLUSION: Oral malodor increased during fixed orthodontic treatments and reached a critical level 7 months later. PMID- 26847701 TI - KCTD12 Regulates Colorectal Cancer Cell Stemness through the ERK Pathway. AB - Targeting cancer stem cells (CSCs) in colorectal cancer (CRC) remains a difficult problem, as the regulation of CSCs in CRC is poorly understood. Here we demonstrated that KCTD12, potassium channel tetramerization domain containing 12, is down-regulated in the CSC-like cells of CRC. The silencing of endogenous KCTD12 and the overexpression of ectopic KCTD12 dramatically enhances and represses CRC cell stemness, respectively, as assessed in vitro and in vivo using a colony formation assay, a spheroid formation assay and a xenograft tumor model. Mechanistically, KCTD12 suppresses CRC cell stemness markers, such as CD44, CD133 and CD29, by inhibiting the ERK pathway, as the ERK1/2 inhibitor U0126 abolishes the increase in expression of CRC cell stemness markers induced by the down regulation of KCTD12. Indeed, a decreased level of KCTD12 is detected in CRC tissues compared with their adjacent normal tissues and is an independent prognostic factor for poor overall and disease free survival in patients with CRC (p = 0.007). Taken together, this report reveals that KCTD12 is a novel regulator of CRC cell stemness and may serve as a novel prognostic marker and therapeutic target for patients with CRC. PMID- 26847703 TI - Solid-state optical refrigeration to sub-100 Kelvin regime. AB - Since the first demonstration of net cooling twenty years ago, optical refrigeration of solids has progressed to outperform all other solid-state cooling processes. It has become the first and only solid-state refrigerator capable of reaching cryogenic temperatures, and now the first solid-state cooling below 100 K. Such substantial progress required a multi-disciplinary approach of pump laser absorption enhancement, material characterization and purification, and thermal management. Here we present the culmination of two decades of progress, the record cooling to ~ 91 K from room temperature. PMID- 26847702 TI - Impairing autophagy in retinal pigment epithelium leads to inflammasome activation and enhanced macrophage-mediated angiogenesis. AB - Age-related decreases in autophagy contribute to the progression of age-related macular degeneration (AMD). We have now studied the interaction between autophagy impaired in retinal pigment epithelium (RPE) and the responses of macrophages. We find that dying RPE cells can activate the macrophage inflammasome and promote angiogenesis. In vitro, inhibiting rotenone-induced autophagy in RPE cells elicits caspase-3 mediated cell death. Co-culture of damaged RPE with macrophages leads to the secretion of IL-1beta, IL-6 and nitrite oxide. Exogenous IL-6 protects the dysfunctional RPE but IL-1beta causes enhanced cell death. Furthermore, IL-1beta toxicity is more pronounced in dysfunctional RPE cells showing reduced IRAK3 gene expression. Co-culture of macrophages with damaged RPE also elicits elevated levels of pro-angiogenic proteins that promote ex vivo choroidal vessel sprouting. In vivo, impaired autophagy in the eye promotes photoreceptor and RPE degeneration and recruitment of inflammasome-activated macrophages. The degenerative tissue environment drives an enhanced pro angiogenic response, demonstrated by increased size of laser-induced choroidal neovascularization (CNV) lesions. The contribution of macrophages was confirmed by depletion of CCR2(+) monocytes, which attenuates CNV in the presence of RPE degeneration. Our results suggest that the interplay between perturbed RPE homeostasis and activated macrophages influences key features of AMD development. PMID- 26847704 TI - Effect of tumor volume on the enhancement pattern of parathyroid adenoma on parathyroid four-dimensional CT. AB - INTRODUCTION: The purpose of this study is to assess the effect of tumor volume on the enhancement pattern of parathyroid adenoma (PTA) on four-dimensional computed tomography (4D-CT). METHODS: We analyzed the enhancement patterns of PTA on four-phase 4D-CT in 44 patients. Dependency of the changes of Hounsfield unit values (DeltaHU) on the tumor volumes and clinical characteristics was evaluated using linear regression analyses. In addition, an unpaired t test was used to compare DeltaHU of PTAs between PTA volume >=1 cm(3) and <1 cm(3), thyroid gland, and lymph node. RESULTS: PTA volume based on CT was the strongest factor on the DeltaHUPre to Arterial and DeltaHUArterial to Venous and DeltaHUArterial to Delayed (R (2) = 0.34, 0.25, and 0.32, respectively, P < 0.001 for both). PTA >=1 cm(3) had statistically significant greater enhancement between the unenhanced phase and the arterial phase than PTA <1 cm(3) (mean values +/- standard deviations (SDs) of DeltaHUPre to Arterial, 102.7 +/- 33.7 and 57.5 +/- 28.8, respectively, P < 0.001). PTA >=1 cm(3) showed an early washout pattern on the venous phase, whereas PTA <1 cm(3) showed a progressive enhancement pattern on the venous phase (mean values +/- SDs of DeltaHUArterial to Venous, -13.2 +/- 31.6 and 14.4 +/- 32.7, respectively; P = 0.009). CONCLUSION: The enhancement pattern of PTA on 4D-CT is variable with respect to PTA volume based on CT. Therefore, the enhancement pattern of PTA on 4D-CT requires careful interpretation concerning the tumor volume, especially in cases of PTA <1 cm(3). PMID- 26847706 TI - MiR-137 acts as a tumor suppressor in papillary thyroid carcinoma by targeting CXCL12. AB - Accumulating evidence has shown that aberrantly expressed microRNAs (miRs) are extensively involved in tumorigenesis. microRNA-137 (miR-137) has been reported as a tumor suppressor in various types of cancer. However, the biological function and underlying molecular mechanism of miR-137 in papillary thyroid carcinoma (PTC) remain largely unknown. Therefore, the present study aimed to investigate the expression pattern of miR-137 and its functional significance in PTC. Quantitative RT-PCR (qRT-PCR) assay showed that miR-137 expression was significantly downregulated in human PTC tissues, and its expression was significantly negatively correlated with tumor-node-metastasis (TNM) stage and lymph node metastasis. Functional assays showed that forced expression of miR-137 in PTC cells significantly inhibited proliferation, colony formation, migration and invasion in vitro. Importantly, on the basis of bioinformatic analysis and luciferase reporter assay, we found that miR-137 directly targeted the 3' untranslated region (3'-UTR) of C-X-C motif chemokine 12 (also known as SDF-1) (CXCL12). qRT-PCR and western blot analysis further verified the results and demonstrated that miR-137 could downregulate CXCL12 expression in PTC cells. We also confirmed that CXCL12 expression was increased in PTC tissues and was inversely correlated with miR-137. In addition, our results also showed that downregulation of CXCL12 mimicked the effects of miR-137 overexpression, and upregulation of CXCL12 partially reversed the inhibitory effects of miR-137 in PTC cells. These results showed that miR-137 may function as a tumor suppressor in PTC by targeting CXCL12, suggesting that miR-137 may act as a potential target for PTC treatment. PMID- 26847705 TI - fMRI activation in the middle frontal gyrus as an indicator of hemispheric dominance for language in brain tumor patients: a comparison with Broca's area. AB - INTRODUCTION: Functional MRI (fMRI) can assess language lateralization in brain tumor patients; however, this can be limited if the primary language area-Broca's area (BA)-is affected by the tumor. We hypothesized that the middle frontal gyrus (MFG) can be used as a clinical indicator of hemispheric dominance for language during presurgical workup. METHODS: Fifty-two right-handed subjects with solitary left-hemispheric primary brain tumors were retrospectively studied. Subjects performed a verbal fluency task during fMRI. The MFG was compared to BA for fMRI voxel activation, language laterality index (LI), and the effect of tumor grade on the LI. RESULTS: Language fMRI (verbal fluency) activated more voxels in MFG than in BA (MFG = 315, BA = 216, p < 0.001). Voxel activations in the left hemispheric MFG and BA were positively correlated (r = 0.69, p < 0.001). Mean LI in the MFG was comparable to that in BA (MFG = 0.48, BA = 0.39, p = 0.06). LIs in MFG and BA were positively correlated (r = 0.62, p < 0.001). Subjects with high grade tumors demonstrate lower language lateralization than those with low-grade tumors in both BA and MFG (p = 0.02, p = 0.02, respectively). CONCLUSION: MFG is comparable to BA in its ability to indicate hemispheric dominance for language using a measure of verbal fluency and may be an adjunct measure in the clinical determination of language laterality for presurgical planning. PMID- 26847707 TI - Visceral Obesity is Associated with Poor Prognosis in Pancreatic Adenocarcinoma. AB - An association between obesity and unfavorable outcomes for various types of malignancy has been established. Nevertheless, the impact of visceral obesity (VO) on outcomes in pancreatic cancer is still unknown and controversial. The aim of this study was to uncover an association between VO and pancreatic cancer outcomes. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed and treated in Severance Hospital from January 2006 to December 2011. Compared to the low-VO group (n = 260), the high-VO group (n = 239) was mostly male (68.2% vs. 31.8%, P < 0.001) and was more likely to have current smoking status (29.7% vs. 17.7%, P < 0.001), current alcohol intake status (52.3% vs. 26.4%, P < 0.001) and diabetes mellitus (54.4% vs. 31.9%, P = 0.028). The progression free survival (PFS) and overall survival (OS) were found to be significantly shorter by the Kaplan-Meier method in the high-VO group than in the low-VO group (PFS; P = 0.044, OS: P = 0.013). In addition, the higher percentage of visceral fat was correlated with more lymph node metastasis and shorter OS (P = 0.011 and P = 0.017, respectively). In patients with pancreatic cancer, VO at the time of diagnosis is associated with negative outcomes, such as shorter PFS and OS. PMID- 26847710 TI - Superhalogen properties of BS2(-) and BSO(-): photoelectron spectroscopy and theoretical calculations. AB - We investigate BS2(-) and BSO(-) clusters using photoelectron spectroscopy and theoretical calculations. The electron affinities of BS2 and BSO are measured to be 3.80 +/- 0.03 and 3.88 +/- 0.03 eV, respectively, higher than those of halogen atoms. Thus, BS2 and BSO can be considered as superhalogens. The comparison of experimental and theoretical results confirmed that the ground state structures of BS2(-), BSO(-), and their neutrals are all linear. Analyses of natural bond orbitals suggest that both BS2(-) and BSO(-) have dual 3c-4e pi hyperbonds. PMID- 26847709 TI - Chemotherapy-Induced Fatigue Correlates With Higher Fatigue Scores Before Treatment. AB - PURPOSE: Cancer chemotherapy can induce fatigue in about 20% to 30% of patients. So far, there is very little information as to the predictors of chemotherapy induced fatigue (CIF). We evaluated potential predictors of CIF in a sample of patients with cancer with several types of solid tumors scheduled to receive chemotherapy according to institutional protocols. METHODS: Before their first and second chemotherapy cycles, patients answered to the Brief Fatigue Inventory (BFI), Chalder, Mini Nutritional Assessment (MNA), Stress thermometer, and HADS questionnaires as well as provided blood samples for inflammatory markers. RESULTS: We evaluated 52 patients, 37 (71%) were female and mean age was 53 years. The most common tumors were breast cancer 21 (40%) and gastrointestinal tumors 12 (23%). Although 14 (25.2%) patients had an increase in their fatigue BFI scores equal or above 3 points from baseline, we observed no significant overall differences between BFI scores before and after chemotherapy. The only 2 factors associated with an increase of 3 points in the BFI scores after chemotherapy were race and higher baseline BFI levels. By multivariate analysis, overall BFI and Chalder scores after chemotherapy also correlated significantly with their respective baseline scores before treatment. HADS scores before treatment correlated with overall BFI scores postchemotherapy, whereas MNA scores before chemotherapy and female sex correlated with higher Chalder scores after treatment. CONCLUSION: We conclude that fatigue induced by chemotherapy is common and consistently associated with higher fatigue scores before treatment. Screening for fatigue before chemotherapy may help to identify patients who are prone to develop CIF. PMID- 26847708 TI - Depression diagnosed by the mini international neuropsychiatric interview plus (MINI) in patients with chronic obstructive pulmonary disease: relationship with functional capacity and quality of life. AB - BACKGROUND: The prevalence of depression in patients with chronic obstructive pulmonary disease (COPD) is associated with a worsening of prognosis. Most studies classify COPD patients as depressive or non-depressive based on symptoms, rather than on a diagnosis using specific tools. Thus, the aim of this study was to determine the impact of depression, as diagnosed by the Mini International Neuropsychiatric Interview Plus (MINI), on functional capacity estimated by the 6 minute walk test (6MWT) and unsupported upper-limb exercise test, and quality of life estimated by Saint George's Respiratory Questionnaire (SGRQ), among patients with COPD. RESULTS: Using the MINI as a diagnostic tool, 22.2 % of all patients (6.6 % of all men and 41.6 % of all women) were diagnosed with depression. No significant differences were found between depressive and non-depressive patients with regard to anthropometric measurements, lung function, functional capacity, or quality of life variables. The best models for the dependent variables representing functional capacity and quality of life revealed that the covariates SGRQTOTAL and gender (R(2) = 16.7 %) were significant in explaining the response variable for functional capacity of the upper limbs. Results also showed that age, monthly income, insomnia, and the results of a 6MWT were significant in explaining overall quality of life (R(2) = 46 %), and that the percentage of the predicted forced expiratory volume in the first second post-bronchodilator and gender were significant in explaining walking distance (R(2) = 22 %). Depression, as diagnosed by the MINI, was not significant in explaining any of the dependent variables. CONCLUSIONS: Despite a high prevalence of depression in COPD patients, especially in women, depression, as diagnosed by the MINI, was not correlated with functional capacity tests or quality of life in patients with moderate to very severe COPD in the present study. This suggests that depression identified by this diagnostic test may be more accurate than depression diagnosed by tests that evaluate symptoms, as they may be influenced by the perceptions of the patient in relation to their health. PMID- 26847711 TI - Spatial analysis of HIV infection and associated individual characteristics in Burundi: indications for effective prevention. AB - BACKGROUND: Adequate resource allocation is critical in the battle against HIV/AIDS, especially in Africa. The determination of the location and nature of HIV services to implement must comply with the geographic, social and behavioral characteristics of patients. We therefore investigated the spatial heterogeneity of HIV prevalence in Burundi and then assessed the association of social and behavioral characteristics with HIV infection accounting for the spatial heterogeneity. METHODS: We used data from the 2010 Demographic and Health Survey. We analyzed these data with a geostatistical approach (which takes into account spatial autocorrelation) by i) interpolating HIV data using the kernel density estimation, ii) identifying the spatial clusters with high and low HIV prevalence using the Kulldorff spatial scan statistics, and then iii) performing a multivariate spatial logistic regression. RESULTS: Overall HIV prevalence was 1.4 %. The interpolated data showed the great spatial heterogeneity of HIV prevalence (from 0 to 10 %), independently of administrative boundaries. A cluster with high HIV prevalence was found in the capital city and adjacent areas (3.9 %; relative risk 3.7, p < 0.001) whereas a cluster with low prevalence straddled two southern provinces (0 %; p = 0.02). By multivariate spatial analysis, HIV infection was significantly associated with the female sex (posterior odds ratio [POR] 1.36, 95 % credible interval [CrI] 1.13-1.64), an older age (POR 1.97, 95 % CrI 1.26 3.08), the level of education (POR 1.50, 95 % CrI 1.22-1.84), the marital status (POR 1.86, 95 % CrI 1.23-2.80), a higher wealth index (POR 2.11, 95 % CrI 1.77 2.51), the sexual activity (POR 1.76, 95 % CrI 1.04-2.96), and a history of sexually transmitted infection (POR 2.03, 95 % CrI 1.56-2.64). CONCLUSIONS: Our study, which shows where and towards which populations HIV resources should be allocated, could help national health policy makers develop an effective HIV intervention in Burundi. Our findings support the strategy of the Joint United Nations Programme on HIV/AIDS (UNAIDS) for country-specific, in-depth analyses of HIV epidemics to tailor national prevention responses. PMID- 26847712 TI - Load-dependent modulation of non-muscle myosin-2A function by tropomyosin 4.2. AB - Tropomyosin isoforms play an important role in the organisation of cytoplasmic actomyosin complexes in regard to function and cellular localisation. In particular, Tpm4.2 is upregulated in rapidly migrating cells and responsible for the specific recruitment of the cytoplasmic class-2 myosin NM-2A to actin filaments during the formation of stress fibres. Here, we investigate how the decoration of F-actin with Tpm4.2 affects the motor properties of NM-2A under conditions of low and high load. In the absence of external forces, decoration of actin filaments with Tpm4.2 does not affect the gated release of ADP from NM-2A and the transition from strong to weak actin-binding states. In the presence of resisting loads, our results reveal a marked increase in the mechanosensitive gating between the leading and trailing myosin head. Thereby, the processive behaviour of NM-2A is enhanced in the presence of resisting loads. The load- and Tpm4.2-induced changes in the functional behaviour of NM-2A are in good agreement with the role of this myosin in the context of stress fibres and the maintenance of cellular tension. PMID- 26847714 TI - Ectopic expression of SlAGO7 alters leaf pattern and inflorescence architecture and increases fruit yield in tomato. AB - ARGONAUTE7 (AGO7), a key regulator of the trans-acting small interfering RNAs (ta siRNA) pathway, plays a conserved role in controlling leaf pattern among species. However, little is known about the ta-siRNA pathway in regulating inflorescence architecture and fruit yield. In this study, we characterized the expression pattern, subcellular localization and developmental functions of SlAGO7 in tomato (Solanum lycopersicum). Overexpressing SlAGO7 in tomato exhibited pleiotropic phenotypes, including improved axillary bud formation, altered leaf morphology and inflorescence architecture, and increased fruit yield. Cross-sectioning of leaves showed that the number of vascular bundles was significantly increased in 35:SlAGO7 lines. Overexpression of SlAGO7 increased the production of ta-siRNA, and repressed the expression ta-siRNA-targeted genes (SlARF2a, SlARF2b, SlARF3 and SlARF4). Further analysis showed that overexpression of SlAGO7 alters the expression of key genes implicated in leaf morphology, inflorescence architecture, auxin transport and signaling. In addition, the altered auxin response of 35:SlAGO7 lines were also investigated. These results suggested that SlAGO7 plays a positive role in determining inflorescence architecture and fruit yield though the ta-siRNA pathway. Therefore, SlAGO7 represents a useful gene that can be incorporated in tomato breeding programs for developing cultivars with yield potential. PMID- 26847713 TI - Diabetes, hyperglycemia, and the burden of functional disability among older adults in a community-based study. AB - BACKGROUND: There is a need for continued surveillance of diabetes-related functional disability. In the present study, we examined associations between diabetes, hyperglycemia, and the burden of functional disability in a community based population. METHODS: A cross-sectional analysis was conducted of 5035 participants who attended Visit 5 (2011-13) of the Atherosclerosis Risk in Communities study. Functional disability was dichotomously defined by any self reported difficulty performing 12 tasks essential to independent living grouped into four functional domains. Associations of diagnosed diabetes (via self report) and undiagnosed diabetes and prediabetes (via HbA1c) with functional disability were evaluated using Poisson regression. RESULTS: Participants had a mean age of 75 years, 42 % were male, 22 % were Black, and 31 % had diagnosed diabetes. Those with diagnosed diabetes had a significantly greater burden of functional disability than those without diabetes, even after adjustment for demographics, health behaviors, and comorbidities: prevalence ratios (95 % confidence intervals) were 1.24 (1.15, 1.34) for lower extremity mobility, 1.14 (1.07, 1.21) for general physical activities, 1.33 (1.16, 1.52) for instrumental activities of daily living (ADL), and 1.46 (1.24, 1.73) for ADL (all P < 0.05). The associations of undiagnosed diabetes and prediabetes with disability were not statistically significant (all P > 0.05). CONCLUSIONS: Among older adults, the burden of functional disability associated with diabetes was not entirely explained by known risk factors, including comorbidities. Hyperglycemia below the threshold for the diagnosis of diabetes was not associated with disability. Research into effective strategies for the prevention of functional disability among older adults with diabetes is needed. PMID- 26847715 TI - Unexplained Recurrent Miscarriage and Recurrent Implantation Failure: Is There a Place for Immunomodulation? AB - To describe and analyze the benefit of immunomodulatory drugs for recurrent miscarriages and implantation failures. The literature research was conducted in Medline, Embase and Cochrane Library concerning recurrent miscarriages and implantation failures and steroids, progesterone, intralipids, TNF-alpha antagonists, G-CSF, hydroxychloroquine, intravenous immunoglobulins, endometrial scratching. Using meta-analysis, modest benefit was found for progesterone to obtain a live birth, with odds ratio at 1.38 (95% CI: 1.07-1.77) and significant heterogeneity (P = 0.01, I(2) = 78%). In early >=3 miscarriages, patients treated by TNF-alpha antagonists (adalimumab or etanercept; n = 17) combined with low dose aspirin, heparin and intravenous immunoglobulins have a live births of 71% (12/17), vs 19% with aspirin+heparin (4/21) (P = 0.0026). Sixty-eight patients with unexplained recurrent miscarriage were randomized to receive either G-CSF (filgastrim, Neupogen, 1 MU/kg/day SC, n = 35) after the ovulation until the 9th weeks of gestation or placebo (n = 33). Among patients treated with G-CSF, 29/35 (82.8%) have live birth and 16/33 (48.5%) of controls (P = 0.006). Among 200 women with recurrent miscarriages and implantation failure treated with intralipids, the pregnancy rate was 52%, with pregnancy ongoing/live birth rate at 91%. The physiopathological rational for immunotolerance failure in this topic raise the need to demonstrate the efficacy of immunomodulatory drugs, define the patients subsets and develop treatment strategies. PMID- 26847716 TI - Substituting Fe for two of the four Mn ions in photosystem II-effects on water oxidation. AB - We have investigated the interaction of Fe(II) cations with Ca-depleted PSII membranes (PSII[-Ca,4Mn]) in the dark and found that Fe(II) incubation removes 2 of 4 Mn ions from the tetranuclear Mn cluster of the photosynthetic O2-evolving complex (OEC). The reduction of Mn ions in PSII(-Ca,4Mn) by Fe(II) and the concomitant release of two Mn(II) cations is accompanied by the binding of newly generated Fe(III) in at least one vacated Mn site. Flash-induced chlorophyll (Chl) fluorescence yield measurements of this new 2Mn/nFe cluster (PSII[ Ca,2Mn,nFe]) show that charge recombination in the presence of 3-(3,4 dichlorophenyl)-1,1-dimethylurea (DCMU) occurs between Qa (-) and the remaining Mn/Fe cluster (but not YZ (?)) in the OEC, and extraction of 2 Mn occurs uniformly in all PSII complexes. No O2 evolution is observed, but the heteronuclear metal cluster in PSII(-Ca,2Mn,nFe) samples is still able to supply electrons for reduction of the exogenous electron acceptor, 2,6 dichlorophrenolindophenol, by photooxidizing water and producing H2O2 in the absence of an exogenous donor as seen previously with PSII(-Ca,4Mn). Selective extraction of Mn or Fe cations from the 2Mn/nFe heteronuclear cluster demonstrates that the high-affinity Mn-binding site is occupied by one of the iron cations. It is notable that partial water-oxidation function still occurs when only two Mn cations are present in the PSII OEC. PMID- 26847717 TI - Functional characterization of the oxidative capacity of mitochondria and glycolytic assessment in benthic aquatic organisms. AB - The metabolism of benthic aquatic invertebrates, populating transitional water ecosystems, is influenced by both physiological and environmental factors, thus involving an adjustment of physiological processes which has a metabolic cost. In order to discover changes in metabolic pathways in response to specific factors, it's firstly necessary characterizing the principal cellular metabolic activities of the small benthic aquatic organisms. We approach here the bioenergetic state issue of two benthic organisms, i.e. Lekanesphaera monodi and Gammarus insensibilis, evidencing that no apparent and statistically significative differences between them in aerobic as well in glycolytic capacities are detected, except for COX activity. PMID- 26847718 TI - Arginine ADP-ribosyltransferase 1 promotes angiogenesis in colorectal cancer via the PI3K/Akt pathway. AB - Arginine adenosine diphosphate (ADP)-ribosyl-transferase 1 (ART1) is known to play an important role in many physiological and pathological processes. Previous studies have demonstrated that ART1 promotes proliferation, invasion and metastasis in colon carcinoma. However, it was unclear whether ART1 is involved in angiogenesis in cases of colorectal cancer (CRC). In the present study, lentiviral vector-mediated ART1-cDNA or ART1-shRNA were transfected into LoVo cells, and the LoVo cells transfected with ART1-cDNA or ART1-shRNA were co cultured with human umbilical vein endothelial cells (HUVECs) to determine the influence of ART1 on HUVECs. The proliferation, migration and angiogenesis of HUVECs were monitored using a cell counting kit-8 assay, a Transwell migration assay and immunohistochemical analysis in intrasplenic allograft tumors, respectively. Hypoxia-inducible factor 1-alpha (HIF-1alpha), total (t-)Akt, phosphorylated (p-)Akt, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) expression levels were detected via western blot analysis. Our results revealed that HUVECs which were co-cultured with ART1-cDNA LoVo cells showed higher proliferation, migration and angiogenic abilities, but a reduction was noted in those cultured with ART1-shRNA LoVo cells; p-Akt, HIF 1alpha, VEGF and bFGF expression was increased in HUVECs cultured with ART1-cDNA transfected LoVo cells, but reduced in ART1-shRNA-transfected LoVo cells. In a mouse xenograft model, we noted that the tumor microvessel density (MVD) was significantly increased in intrasplenic transplanted ART1-cDNA CT26 tumors but decreased in intrasplenic transplanted ART1-shRNA tumors. These data suggest that ART1 promoted the expression of HIF-1alpha via the Akt pathway in tumor cells. It also upregulated VEGF and bFGF and enhanced angiogenesis in HUVECs. Thus, we suggest that ART1 plays an important role in the invasion of CRC cells and the metastasis of CRC. PMID- 26847719 TI - Nanoplasmonic probes of RNA folding and assembly during pre-mRNA splicing. AB - RNA splicing plays important roles in transcriptome and proteome diversity. Herein, we describe the use of a nanoplasmonic system that unveils RNA folding and assembly during pre-mRNA splicing wherein the quantification of mRNA splice variants is not taken into account. With a couple of SERS-probes and plasmonic probes binding at the boundary sites of exon-2/intron-2 and intron-2/exon-3 of the pre-mature RNA of the beta-globin gene, the splicing process brings the probes into the plasmonic bands. For plasmonic probes, a plasmon shift increase of ~29 nm, corresponding to intron removal and exon-2 and exon-3 connection to form the mRNA molecule, is measured by plasmonic coupling. The increased scattering intensity and surface-enhanced Raman scattering (SERS) fingerprinting reveal the clear dynamics of pre-mRNA splicing. Moreover, a time-resolved experiment of individual RNA molecules exhibited a successful splicing and an inhibited splicing event by 33 MUM biflavonoid isoginkgetin, a general inhibitor of RNA splicing. The results suggest that the RNA splicing is successfully monitored with the nanoplasmonic system. Thus, this platform can be useful for studying RNA nanotechnology, biomolecular folding, alternative splicing, and maturation of microRNA. PMID- 26847720 TI - Determining national greenhouse gas emissions from waste-to-energy using the Balance Method. AB - Different directives of the European Union require operators of waste-to-energy (WTE) plants to report the amount of electricity that is produced from biomass in the waste feed, as well as the amount of fossil CO2 emissions generated by the combustion of fossil waste materials. This paper describes the application of the Balance Method for determining the overall amount of fossil and thus climate relevant CO2 emissions from waste incineration in Austria. The results of 10 Austrian WTE plants (annual waste throughput of around 2,300 kt) demonstrate large seasonal variations in the specific fossil CO2 emissions of the plants as well as large differences between the facilities (annual means range from 32+/-2 to 51+/-3 kg CO(2,foss)/GJ heating value). An overall amount of around 924 kt/yr of fossil CO2 for all 10 WTE plants is determined. In comparison biogenic (climate neutral) CO2 emissions amount to 1,187 kt/yr, which corresponds to 56% of the total CO2 emissions from waste incineration. The total energy input via waste feed to the 10 facilities is about 22,500 TJ/yr, of which around 48% can be assigned to biogenic and thus renewable sources. PMID- 26847721 TI - B cells shed light on diminished vaccine responses in obesity. PMID- 26847722 TI - Interposition of a connective tissue graft or a collagen matrix to enhance wound stability - an experimental study in dogs. AB - AIM: The aim of this study was to evaluate the role of a connective tissue graft (CTG) or a collagen matrix (CM) interpositioned between flaps and non-shedding hard surfaces on wound stability. MATERIAL AND METHODS: Sixty bone dehiscence defects were prepared in five Beagle dogs. Three treatments were performed in 12 sites per dog: (1) repositioned flaps were sutured onto instrumented dentin surfaces (control), (2) repositioning of flaps with an interpositioned CTG and (3) repositioning of flaps with the application of a CM. To allow postoperative healing with n = 5 for 1, 3, 7 and 14 days before evaluation, the sutures were removed, incision lines retraced and tensile forces applied to the flaps. The minimum magnitude of forces required to detach the flaps from the wound bed was recorded. RESULTS: After 1 week of healing, 6 N had to be applied to disrupt flaps from their wound bed in the CTG group. In the control group, a similar magnitude of resistance was achieved after 2 weeks (6.1 N). Flap resistance to tearing was highest in the CTG group (maximum 9.1 N) 2 weeks postoperatively. On the third postoperative day, the mean tearing forces of all groups differed significantly, displaying a 50% lower resistance to tearing in the CM compared to the CTG group. In comparison, flap resistance to tearing forces established earlier and in higher magnitude in sites with an interpositioned CTG than in flaps repositioned on dentin or CM. CONCLUSIONS: Application of a CTG, sutured to a non-shedding hard surface, significantly increased flap resistance to tearing when applying disrupting forces compared to controls. A less pronounced effect was achieved by interpositioning of a CM. PMID- 26847723 TI - Kaempferol induces apoptosis in HepG2 cells via activation of the endoplasmic reticulum stress pathway. AB - Kaempferol is a flavonoid compound that has gained importance due to its antitumor properties; however, the underlying mechanisms remain to be fully understood. The present study aimed to investigate the molecular mechanisms of the antitumor function of kaempferol in HepG2 hepatocellular carcinoma cells. Kaempferol was determined to reduce cell viability, increase lactate dehydrogenase activity and induce apoptosis in a concentration- and time dependent manner in HepG2 cells. Additionally, kaempferol-induced apoptosis possibly acts via the endoplasmic reticulum (ER) stress pathway, due to the significant increase in the protein expression levels of glucose-regulated protein 78, glucose-regulated protein 94, protein kinase R-like ER kinase, inositol-requiring enzyme 1alpha, partial activating transcription factor 6 cleavage, caspase-4, C/EBP homologous protein (CHOP) and cleaved caspase-3. The pro-apoptotic activity of kaempferol was determined to be due to induction of the ER stress-CHOP pathway, as: i) ER stress was blocked by 4-phenyl butyric acid (4 PBA) pretreatment and knockdown of CHOP with small interfering RNA, which resulted in alleviation of kaempferol-induced HepG2 cell apoptosis; and ii) transfection with plasmid overexpressing CHOP reversed the protective effect of 4 PBA in kaempferol-induced HepG2 cells and increased the apoptotic rate. Thus, kaempferol promoted HepG2 cell apoptosis via induction of the ER stress-CHOP signaling pathway. These observations indicate that kaempferol may be used as a potential chemopreventive treatment strategy for patients with hepatocellular carcinoma. PMID- 26847724 TI - Immunity of the greater wax moth Galleria mellonella. AB - Investigation of insect immune mechanisms provides important information concerning innate immunity, which in many aspects is conserved in animals. This is one of the reasons why insects serve as model organisms to study virulence mechanisms of human pathogens. From the evolutionary point of view, we also learn a lot about host-pathogen interaction and adaptation of organisms to conditions of life. Additionally, insect-derived antibacterial and antifungal peptides and proteins are considered for their potential to be applied as alternatives to antibiotics. While Drosophila melanogaster is used to study the genetic aspect of insect immunity, Galleria mellonella serves as a good model for biochemical research. Given the size of the insect, it is possible to obtain easily hemolymph and other tissues as a source of many immune-relevant polypeptides. This review article summarizes our knowledge concerning G. mellonella immunity. The best characterized immune-related proteins and peptides are recalled and their short characteristic is given. Some other proteins identified at the mRNA level are also mentioned. The infectious routes used by Galleria natural pathogens such as Bacillus thuringiensis and Beauveria bassiana are also described in the context of host-pathogen interaction. Finally, the plasticity of G. mellonella immune response influenced by abiotic and biotic factors is described. PMID- 26847725 TI - Inflammation: maladies, models, mechanisms and molecules. AB - The continued focus of attention on the diversity of mechanisms underpinning inflammation has improved our understanding of the potential to target specific pathways in the inflammatory network to achieve meaningful therapeutic gains. In this themed issue of the British Journal of Pharmacology our scope was deliberately broad, ranging across both acute and chronic disease in various organs. Pro- and anti-inflammatory mechanisms receive attention as does the phenotype of macrophages. Whilst the manifestations of neuro-inflammation are less obvious than those in peripheral tissues, central innate and adaptive immunity in brain and the M1/M2 phenotypes of microglia are topics of special interest. The contributions to the inflammatory milieu of cytokines, chemokines and associated signalling cascades are considered. Overall, the coverage herein advances the basic science underpinning our understanding of inflammation and emphasizes its importance in different pathologies. PMID- 26847726 TI - Glucose and acute exercise influence factors secreted by circulating angiogenic cells in vitro. AB - Circulating angiogenic cells (CAC) influence vascular repair through the secretion of proangiogenic factors and cytokines. While CAC are deficient in patients with diabetes and exercise has a beneficial effect on CACs, the impact of these factors on paracrine secretion from CAC is unknown. We aimed to determine whether the in vitro secretion of selected cytokines and nitric oxide (NO) from CAC is influenced by hyperglycemia and acute exercise. Colony-forming unit CAC (CFU-CAC) were cultured from young active men (n = 9, 24 +/- 2 years) at rest and after exercise under normal (5 mmol/L) and elevated (15 mmol/L) glucose. Preliminary relative multiplex cytokine analysis revealed that CAC conditioned culture media contained three of six measured cytokines: transforming growth factor-beta-1 (TGFbeta1), tumor necrosis factor alpha (TNFalpha), and monocyte chemotactic protein-1 (MCP-1). Single quantitative cytokine analysis was used to determine the concentration of each cytokine from the four conditions. NO was measured via Griess assay. There was a significant effect of CAC exposure to in vivo exercise on in vitro TGFbeta1 secretion (P = 0.024) that was independent of glucose concentration. There was no effect of glucose or acute exercise on TNFalpha or MCP-1 concentration (both P > 0.05). The concentration of NO from CFU CAC cultured in elevated glucose was lower following acute exercise (P = 0.002) suggesting that exercise did not maintain NO secretion under hyperglycemic conditions. Our results identify paracrine signaling factors that may be responsible for the proangiogenic function of CFU-CAC and an influence of acute exercise and elevated glucose on CFU-CAC soluble factor secretion. PMID- 26847727 TI - Liver mitochondrial function in ZDF rats during the early stages of diabetes disease. AB - The aim of this study was to characterize the early alterations of the liver mitochondrial function in ZDF (fa/fa) rats that develop diabetes compared to that of their lean counterparts ZDF (fa/+). Liver mitochondrial function was examined in 11- and 14-week-old ZDF (fa/fa) and ZDF lean (fa/+) rats. Oxygen consumption, H2O2 release, calcium retention capacity (CRC), membrane potential, membrane fluidity, and fatty acid composition were analyzed. State 3 oxygen consumption with palmitoyl-carnitine increases between 11 and 14 weeks of age in lean but not in diabetic animals. This response was not seen with other substrates, suggesting that the use of fatty acids is impaired in diabetic rats. H2O2 release was lower in 14-week-old ZDF (fa/fa) rats as compared to ZDF lean (fa/+). These changes were not associated with differences in enzymatic activities of the respiratory complexes, suggesting regulatory mechanisms independent of their expression levels. Membrane fluidity and composition analyses show only slight effects linked to diabetes progression. The most salient feature was a reduction in CRC in the presence of CsA, an effect reflecting PTP dysregulation. Our data suggest few changes of mitochondrial function in ZDF fa/fa rats. At the age of 11 weeks, liver mitochondria have mainly a reduced effect of CsA on CRC. PMID- 26847729 TI - Treatment principles for peritoneal surface malignancies. AB - A paradigm shift has recently occurred in the clinical management of peritoneal surface malignancies (PSM). Once regarded as end-stage disseminated conditions only to be palliated, PSM are now increasingly recognized as local-regional disease entities amenable to potentially curative therapies. Better knowledge of the natural history and patterns of disease-progression has evolved into a novel treatment approach combining aggressive cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy, to treat the microscopic residual disease. Such a complex comprehensive treatment has reportedly resulted in a survival improvement over historical controls, and it is gaining an increasing acceptance as standard of care for selected patients with peritoneal metastases from gastrointestinal and gynecological tumor and rare primary peritoneal malignancies. This article addresses the rational bases supporting the comprehensive treatment of PSM. The biology and patho-physiology of peritoneal tumor dissemination, with their implication on surgical and local-regional management are reviewed. The cytoreductive surgical procedures and intraperitoneal chemotherapy administration techniques are described, together with the theoretical principles from which have originated. The main controversial issues in the operative management of PSM are discussed, focusing on the technical variants adopted in our institution. The most recent literature data on both patient selection and appropriate indications for combined treatment are presented. Additionally, a brief overview of treatment results and long-term outcomes following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in the different PSM is provided. PMID- 26847728 TI - Glucose-loading reduces bone remodeling in women and osteoblast function in vitro. AB - Aging is associated with a reduction in osteoblast life span and the volume of bone formed by each basic multicellular unit. Each time bone is resorbed, less is deposited producing microstructural deterioration. Aging is also associated with insulin resistance and hyperglycemia, either of which may cause, or be the result of, a decline in undercarboxylated osteocalcin (ucOC), a protein produced by osteoblasts that increases insulin sensitivity. We examined whether glucose loading reduces bone remodeling and ucOC in vivo and osteoblast function in vitro, and so compromises bone formation. We administered an oral glucose tolerance test (OGTT) to 18 pre and postmenopausal, nondiabetic women at rest and following exercise and measured serum levels of bone remodeling markers (BRMs) and ucOC. We also assessed whether increasing glucose concentrations with or without insulin reduced survival and activity of cultured human osteoblasts. Glucose-loading at rest and following exercise reduced BRMs in pre and postmenopausal women and reduced ucOC in postmenopausal women. Higher glucose correlated negatively, whereas insulin correlated positively, with baseline BRMs and ucOC. The increase in serum glucose following resting OGTT was associated with the reduction in bone formation markers. D-glucose (>10 mmol L(-1)) increased osteoblast apoptosis, reduced cell activity and osteocalcin expression compared with 5 mmol L(-1). Insulin had a protective effect on these parameters. Collagen expression in vitro was not affected in this time course. In conclusion, glucose exposure reduces BRMs in women and exercise failed to attenuate this suppression effect. The suppressive effect of glucose on BRMs may be due to impaired osteoblast work and longevity. Whether glucose influences material composition and microstructure remains to be determined. PMID- 26847730 TI - Amyloid deposition in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue: A clinicopathologic study of 5 cases. AB - Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) is the most common subtype of marginal zone lymphoma (MZL), with stomach being the most frequent primary site, followed by salivary gland, lung and ocular adnexa. Although clinically indolent, MALT lymphoma has the potential of local recurrence and systemic spread. Amyloid deposition is a very unusual complication of MALT lymphoma. In this study, we report clinicopathologic features of 5 cases of MALT lymphomas with associated amyloid deposits. One case showed amyloid deposits in the primary lesion; the other four cases showed amyloid deposits only in recurrences. Previous studies suggest that the amyloid deposits do not implicate worse prognosis. In our study, although amyloid deposits were focal and organ confined, one patient had extensive deposits of amyloid in the large bowel wall leading to bowel perforation and another patient developed significant peripheral neuropathy due to amyloid deposits in the brachial plexus. In conclusion, amyloid deposits in MALT lymphomas are rare and organ/tumour confined. However, complications can be critical and cause considerable morbidity. Therefore, pathologists should be aware of the association between MALT lymphoma and amyloid deposition, and clinical follow up is warranted. PMID- 26847731 TI - Intraoperative consultation of central nervous system lesions. Frozen section, cytology or both? AB - OBJECTIVE: Frozen section is the traditional method of assessing central nervous system (CNS) lesions intraoperatively. Our aim is to determine the diagnostic accuracy of frozen section and/or cytological evaluation of CNS lesions in our center. STUDY DESIGN: A total of 157 patients with CNS lesions underwent open surgical biopsy or excision in our center during a period of 2 years (2012-2013). All specimens were studied cytologically; of these specimens, 146 cases were also examined by frozen section. Cytology and frozen section slides were studied separately by two general pathologists who were blind to final diagnoses. The final diagnoses were based on permanent sections and IHC studies. RESULTS: The accuracy rates of frozen section analysis and cytological evaluation were 87% and 86%, respectively. If the two methods were considered together, the accuracy rate improved to about 95%. CONCLUSIONS: Cytological evaluation is an acceptable alternative to frozen section analysis and also a great supplement to the diagnosis of CNS lesions. PMID- 26847732 TI - Survey on the risk awareness of german pig and cattle farmers in relation to dealing with MRSA and antibiotics. AB - INTRODUCTION: The danger surrounding methicillin-resistant Staphylococcus aureus (MRSA) has been well known for decades. Although MRSA was initially only associated with hospitals, livestock-associated MRSA is being increasingly connected to the way food-supplying animals are treated. However, little is yet known about farmers' risk awareness and their knowledge of MRSA. Hence, the goal of this study was to discover farmers' perceptions of MRSA. MATERIALS AND METHODS: Two successive studies were performed. Study I analysed the connection between the attitudes of cattle and pig farmers towards MRSA complications and characteristics such as age and vocational training. Study II dealt with the connection between contact frequency with livestock and the risk of MRSA colonisation. RESULTS: For Study I, 101 questionnaires were completed. Analysis showed that the participants' education level (p=0.042, alpha=0.05) and the animal species kept on their farm (p=0.045, alpha=0.05) significantly influenced their perceptions. Screening results from 157 participants within Study II showed that contact frequency and the participants' particular profession were significantly decisive for MRSA prevalence (contact frequency: p=0.000, professional branch: p=0.000, OR=11.966, alpha=0.05). DISCUSSION: The results show a high degree of risk consciousness and responsibility among farmers. However, it is assumed that most farmers who took part in the studies were interested parties. Thus, the study results are valid only for the chosen livestock holdings. Ultimately, educational work is still needed. Joint projects between economics and science offer a good platform to spark farmers' interest in the MRSA problem, as well as to inform and enlighten them about dangers and connections. Interdisciplinary research will contribute to a better understanding of drug resistance and to reducing the long-term use of antibiotics. PMID- 26847733 TI - Creating arteriovenous fistulas in patients with chronic central venous obstruction. AB - PURPOSE: Central venous obstruction Occlusion (CVO) has been considered a contraindication for creating a vascular access due to fear of developing a swollen extremity. However, many of these individuals developed large collateral veins and are asymptomatic. We report our experience constructing arteriovenous fistulas (AVFs) in these challenging patients. METHODS: Patients with a new AVF constructed in the presence of known CVO were identified. Venous imaging confirmed proximal obstruction and extensive collateral venous return. The AVF was constructed in the extremity with the most favorable ultrasound vessel mapping and collateral central venous outflow. Arterial inflow via the radial artery was utilized when feasible. RESULTS: AVFs associated with known CVO were constructed in 19 patients during an eight-year time period. The mean age was 53 years, 63% were female, and 58% diabetic. Arterial inflow was from the radial artery in 15 patients and the brachial or axillary artery in 5 individuals. Post operative AVF flow volumes were 415-910 mL/min (mean = 640 mL/min). Eight patients (42%) developed some degree of arm edema. Two resolved without intervention. The others required inflow banding (n = 2), outflow branch coiling (n = 1), and/or recanalization with angioplasty (n = 4) of the CVO to resolve swelling. Mean follow-up was 14 months. Two AVFs failed at 8 and 16 months. Primary and cumulative patency rates were 49% and 100% at 12 months and 39% and 80% at 24 months, respectively. CONCLUSIONS: CVO need not preclude the creation of a successful AVF. Extensive venous collaterals and avoiding high-flow AVFs are important elements for success. Cumulative patency was 80% at 24 months. PMID- 26847734 TI - Which arm and vein are more appropriate for single-step, non-fluoroscopic, peripherally inserted central catheter insertion? AB - OBJECTIVE: We investigated which arm and vein led to the most successful outcomes during non-fluoroscopic peripherallyinserted central catheter (PICC) insertion. METHODS: A total of 743 cases from July 2012 to March 2014 were retrospectively reviewed. We also analyzed the following: 1) accessed arm (right or left), 2) accessed vein (cephalic, basilic, or brachial), 3) primary and secondary success rates, 4) causes of failure (location of obstacles), and 5) problemsolving methods for catheter repositioning. RESULTS: The primary success rate was 46.3% (344/743) with 49.4% (123/249) on the right arm and 44.7% (273/494) on the left arm. The secondary success rate was 53.7% (399/743) with 50.6% (126/249) on the right arm and 55.3% (273/494) on the left arm. The causes of failure were 100% (43/43) for the left cephalic vein, 61.5% (8/13) for the right cephalic vein, 50.6% (43/85) for the left brachial vein, and 51.1% (23/45) for the right brachial vein, 51.1% (187/366) for the left basilic vein, and 49.7% (95/191) for the right basilic vein. The failure rate through the left cephalic vein was significantly higher than that for other veins. The most common locations of obstacles were the subclavian vein (28.8%, 115/399), axillary vein (24.3%, 97/399), and brachiocephalic vein (19.3%, 77/399). The most common problem solving methods were with guidewire assistance (74.7%, 298/399), venographic guidance (13.8%, 55/399), and fluoroscopic guidance (11.5%, 46/399). CONCLUSIONS: Right-arm access through the basilic or brachial vein may be more appropriate for successful nonfluoroscopic PICC insertion compared with the access through the left arm and the cephalic vein. PMID- 26847735 TI - Comparison of intensive versus standard hemodialysis central venous catheter dysfunction protocol using rt-PA: a quality assurance initiative. AB - PURPOSE: Catheter locking solutions such as recombinant tissue plasminogen activator (rt-PA) are used to treat and prevent clotting of hemodialysis (HD) catheters during HD treatments and the interdialytic period. However, evidence to guide the use of rt-PA for catheter dysfunction is limited. METHODS: We evaluated outcomes using two catheter dysfunction protocols in a cohort of consecutive prevalent dialysis patients (Jan 2013 to Sep 2014) undergoing HD with a tunneled catheter. In the intensive protocol, rt-PA was administered to all catheters based on blood flow and/or line reversal. In the standard protocol, rt-PA administration was based only on blood flow. The primary outcome was the rate of rt-PA use for catheter malfunction (rt-PA treatment days/1000 total line days; [TLD]). Secondary outcomes included the cost of rt-PA/TLD and the rate of catheter-related bacteremia. RESULTS: There were 26 and 35 patients managed by the intensive and standard protocols, respectively. The rate of rt-PA use was 52/1000 TLD (intensive) versus 39/1000 TLD (standard) (rate ratio 1.30, 95% CI 1.12-1.52 CI, p<0.001). The rate of bacteremia was 0.43 and 0.22/1000 TLD for the intensive and standard protocols, respectively (p = 0.491). The cost of rt-PA was CDN $5.58 and CDN $6.15 per TLD for the intensive protocol and standard protocol groups (p<0.001). CONCLUSIONS: Managing catheter dysfunction based on line reversal and blood flow as opposed to only blood flow was associated with a higher rate of rt-PA use, but at a reduced overall cost. PMID- 26847736 TI - Systematic review of drug eluting balloon angioplasty for arteriovenous haemodialysis access stenosis. AB - BACKGROUND: Native or prosthetic arteriovenous (AV) fistulas are preferred for permanent haemodialysis (HD) access. These are marked with circuit steno occlusive disease leading to dysfunction or even failure. Late failure rates have been reported as high as 50%. Standard angioplasty balloons are an established percutaneous intervention for HD access stenosis. Reported restenosis rates remain high and practice guidelines recommend a wide 6-month primary patency (PP) of at least 50% for any intervention. Neointimal hyperplasia is one of the main causes for access circuit stenosis. Drug eluting balloon (DeB) angioplasty has been proposed as an alternative intervention to reduce restenosis by local drug delivery and possible inhibition of this process. PURPOSE: To systematically assess the reported efficacy and safety of DeB angioplasty in percutaneous management of prosthetic and autologous HD access stenosis. METHODS: Protocol for the review was developed following the PRISMA-P 2015 statement. An electronic database (Medline, EMBASE, Clinical Trials.gov and Cochrane CENTRAL) search was conducted to identify articles reporting on the use of DeB intervention in HD AV access. Backward and forward citation search as well as grey literature search was performed. The MOOSE statement and PRISMA 2009 statement were followed for the reporting of results. Data from the included studies comparing DeBs with non DeBs were pooled using a random effects meta-analysis model and reported separately on randomised and non-randomised studies. RESULTS: Six studies reported on 254 interventions in 162 participants (mean 27 +/- 10 SD). The pooled mean and median duration of follow-up was 12 and 13 months (range 6-24 months). These comprised two randomised control trials (RCTs) and four cohort studies. Participant's mean age was 64 +/- 5 years and 61% were male. Target lesions (TLs) ranged from under 2 mm to 5.9 mm and 51 were reported as de novo stenosis. Device failure described as wasting of the DeB was reported in two studies (55% and 92.8%). At 6 months TL PP was reported between 70% to 97% for DeBs in the RCTs and cohort studies, and 0% to 26% for non-DeBs. TLs treated with DeBs were associated with a higher primary patency at 6 months as compared to non-DeB balloons (RCTs: odds ratio [OR] 0.25, 95% CI 0.08 to 0.77 and I2 = 19%, cohort studies: OR 0.10, 95% CI 0.03 to 0.31 and an I2 = 20%). No procedure-related major or minor complications were reported. CONCLUSIONS: Current literature reports DeBs as being safe and may convey some benefit in terms of improved rate of restenosis when used to treat AV access disease. However, this body of evidence is small and clinically heterogeneous. A large multicentre RCT may help to clarify the role of DeBs in the percutaneous treatment of AV HD access stenosis. PMID- 26847737 TI - A new infraclavicular landmark-based approach to the axillary vein as an alternative method of central venous cannulation. AB - PURPOSE: We developed the new technique of the axillary vein catheterization, which is connected with the determination of only two anatomical points of reference for puncture site identification. The primary outcome of this study was to determine the rate of successful catheterizations and the assessment of procedure success rate, depending on cannulation side as well as physician experience. The secondary objective was to evaluate the early complication rate and to determine whether this method can be used in clinical practice. METHODS: The methodology of this prospective, cohort study included catheterization of the axillary vein via the infraclavicular approach. All procedures were performed by the first two authors, each of whom had different levels of experience with the technique. The choice of the cannulation side was based on clinical factors, and the technique was identical on the right and left sides. RESULTS: The cannulation success rate reached 85.6% (N = 153). The correlation between physician experience and the procedure success rate as well as between cannulation side and procedure success rate were not significant. A common early complication was a puncture of axillary artery (14.4%) with the following proper cannulation in the majority of patients (77.3%, p<0.01, exact test). CONCLUSIONS: The procedure success rate, 85.6% (95% CI [80.0, 91.2%]), is comparable to other landmark-based techniques of the central vein cannulation. The moderately high percentage of axillary artery puncture points out that the approach should be used only as an alternative method to the central vein catheterization. PMID- 26847738 TI - Predictive models for arteriovenous fistula maturation. AB - PURPOSE: Haemodialysis (HD) is a lifeline therapy for patients with end-stage renal disease (ESRD). A critical factor in the survival of renal dialysis patients is the surgical creation of vascular access, and international guidelines recommend arteriovenous fistulas (AVF) as the gold standard of vascular access for haemodialysis. Despite this, AVFs have been associated with high failure rates. Although risk factors for AVF failure have been identified, their utility for predicting AVF failure through predictive models remains unclear. The objectives of this review are to systematically and critically assess the methodology and reporting of studies developing prognostic predictive models for AVF outcomes and assess them for suitability in clinical practice. METHODS: Electronic databases were searched for studies reporting prognostic predictive models for AVF outcomes. Dual review was conducted to identify studies that reported on the development or validation of a model constructed to predict AVF outcome following creation. Data were extracted on study characteristics, risk predictors, statistical methodology, model type, as well as validation process. RESULTS: We included four different studies reporting five different predictive models. Parameters identified that were common to all scoring system were age and cardiovascular disease. CONCLUSIONS: This review has found a small number of predictive models in vascular access. The disparity between each study limits the development of a unified predictive model. PMID- 26847739 TI - Accessing totally implantable venous access systems on the day of placement does not significantly increase the risk of infection. AB - PURPOSE: Totally implantable venous access systems (ports) are commonly placed and have a low complication rate. The most common complication is infection, which can have very negative effects on patients resulting in hospitalization and/or treatment delay in the setting of neoplasm. While a number of variables have been studied in relation to diminishing infectious rates, one remaining question is the effect of accessing the port on day of placement, which is the aim of this retrospective study. MATERIALS AND METHODS: After internal review board approval the electronic medical records of 2,006 patients who underwent port placement between 10/1/2008 and 9/30/2013 were reviewed. Of these patients 628 were excluded as they did not have complete placement and removal data available, leaving 1378 patients in our cohort. RESULTS: There was a significantly longer number of infection-free catheter days in the out-patient cohort as compared to the in-patient cohort (p = 0.027). In-patients mean day after placement when the port was first accessed (DAP) (0.5) was statistically earlier (closer to placement) than the out-patients DAP (7.2) (p<0.0001). However, the increased likelihood of infection could not be explained by DAP (p = 0.2029) even when controlling for in-patient and out-patient status (p = 0.97). CONCLUSIONS: Accessing the port on the day of placement does not significantly contribute to an increased likelihood of infection. This study seems to indicate that placing a port on the first day of outpatient therapy likely optimally balances respect for patient time with infection control. PMID- 26847740 TI - Same day admission for elective cardiac surgery: how to improve outcome with satisfaction and decrease expenses. AB - Admission on the day of surgery for elective cardiac and non-cardiac surgery has been established as a prevalent, critical practice. This approach realizes medical, logistical, psychological and fiscal benefits, and its success is predicated on an effective outpatient pre-operative evaluation. The establishment of a highly functional pre-operative clinic with a comprehensive set-up and efficient logistical pathways is invaluable. This notion has been expanded in recent years to include the entire peri-operative period and the concept of a 'peri-operative anesthesia/surgical home' is gaining popularity and support. Evaluating patients prior to admission for surgery, anesthesiologists can place themselves at the forefront of reducing unnecessary pre-operative hospital admissions, excess lab tests, unneeded consultations, and ultimately decrease the cancellations on the day of surgery. Furthermore, by taking a leadership role in the pre-operative clinic, anesthesiologists place themselves squarely at the forefront of the burgeoning movement for the peri-operative surgical home and continue to cement the indispensability of the anesthesiologist during the entire peri-operative course. The authors present this review as a follow-up describing the successful implementation of a pre-operative same-day cardiac surgery clinic and offer these experiences over the last 8 years as a guide to helping other anesthesiologists do the same. PMID- 26847741 TI - BI-RADS Density Classification From Areometric and Volumetric Automatic Breast Density Measurements. AB - RATIONALE AND OBJECTIVES: The aim of our study was to classify breast density using areometric and volumetric automatic measurements to best match Breast Imaging-Reporting and Data System (BI-RADS) density scores, and determine which technique best agrees with BI-RADS. Second, this study aimed to provide a set of threshold values for areometric and volumetric density to estimate BI-RADS categories. MATERIALS AND METHODS: We randomly selected 537 full-field digital mammography examinations from a population-based screening program. Five radiologists assessed breast density using BI-RADS with all views available. A commercial program calculated areometric and volumetric breast density automatically. We compared automatically calculated density to all BI-RADS density thresholds using area under the receiver operating characteristic curve, and used Youden's index to estimate thresholds in automatic densities, with matching sensitivity and specificity. The 95% confidence intervals were estimated by bootstrapping. RESULTS: Areometric density correlated well with volumetric density (r(2) = 0.76, excluding outliers, n = 2). For the BI-RADS threshold between II and III, areometric and volumetric assessment showed about equal area under the curve (0.94 vs. 0.93). For the threshold between I and II, areometric assessment was better than volumetric assessment (0.91 vs. 0.86). For the threshold between III and IV, volumetric assessment was better than areometric assessment (0.97 vs. 0.92). CONCLUSIONS: Volumetric assessment is equal to or better than areometric assessment for the most clinically relevant thresholds (ie, between scattered fibroglandular and heterogeneously dense, and between heterogeneously dense and extremely dense breasts). Thresholds found in this study can be applied in daily practice to automatic measurements of density to estimate BI-RADS classification. PMID- 26847742 TI - Long-Term Morphological and Microarchitectural Stability of Tissue-Engineered, Patient-Specific Auricles In Vivo. AB - Current techniques for autologous auricular reconstruction produce substandard ear morphologies with high levels of donor-site morbidity, whereas alloplastic implants demonstrate poor biocompatibility. Tissue engineering, in combination with noninvasive digital photogrammetry and computer-assisted design/computer aided manufacturing technology, offers an alternative method of auricular reconstruction. Using this method, patient-specific ears composed of collagen scaffolds and auricular chondrocytes have generated auricular cartilage with great fidelity following 3 months of subcutaneous implantation, however, this short time frame may not portend long-term tissue stability. We hypothesized that constructs developed using this technique would undergo continued auricular cartilage maturation without degradation during long-term (6 month) implantation. Full-sized, juvenile human ear constructs were injection molded from high-density collagen hydrogels encapsulating juvenile bovine auricular chondrocytes and implanted subcutaneously on the backs of nude rats for 6 months. Upon explantation, constructs retained overall patient morphology and displayed no evidence of tissue necrosis. Limited contraction occurred in vivo, however, no significant change in size was observed beyond 1 month. Constructs at 6 months showed distinct auricular cartilage microstructure, featuring a self-assembled perichondrial layer, a proteoglycan-rich bulk, and rounded cellular lacunae. Verhoeff's staining also revealed a developing elastin network comparable to native tissue. Biochemical measurements for DNA, glycosaminoglycan, and hydroxyproline content and mechanical properties of aggregate modulus and hydraulic permeability showed engineered tissue to be similar to native cartilage at 6 months. Patient-specific auricular constructs demonstrated long-term stability and increased cartilage tissue development during extended implantation, and offer a potential tissue-engineered solution for the future of auricular reconstructions. PMID- 26847743 TI - Nuclear accumulation of myocyte muscle LIM protein is regulated by heme oxygenase 1 and correlates with cardiac function in the transition to failure. AB - KEY POINTS: The present study investigated the mechanism associated with impaired cardiac mechanosensing that leads to heart failure by examining the factors regulating muscle LIM protein subcellular distribution in myocytes. In myocytes, muscle LIM protein subcellular distribution is regulated by cell contractility rather than passive stretch via heme oxygenase-1 and histone deacetylase signalling. The result of the present study provide new insights into mechanotransduction in cardiac myocytes. Myocyte mechanosensitivity, as indicated by the muscle LIM protein ratio, is also correlated with cardiac function in the transition to failure in a guinea-pig model of disease. This shows that the loss mechanosensitivity plays an important role during the transition to failure in the heart. The present study provides the first indication that mechanosensing could be modified pharmacologically during the transition to heart failure. ABSTRACT: Impaired mechanosensing leads to heart failure and a decreased ratio of cytoplasmic to nuclear CSRP3/muscle LIM protein (MLP ratio) is associated with a loss of mechanosensitivity. In the present study, we tested whether passive or active stress/strain was important in modulating the MLP ratio and determined whether this correlated with heart function during the transition to failure. We exposed cultured neonatal rat myocytes to a 10% cyclic mechanical stretch at 1 Hz, or electrically paced myocytes at 6.8 V (1 Hz) for 48 h. The MLP ratio decreased by 50% (P < 0.05, n = 4) only in response to electrical pacing, suggesting impaired mechanosensitivity. Inhibition of contractility with 10 MUm blebbistatin resulted in an ~3-fold increase in the MLP ratio (n = 8, P < 0.05), indicating that myocyte contractility regulates nuclear MLP. Inhibition of histone deacetylase (HDAC) signalling with trichostatin A increased nuclear MLP following passive stretch, suggesting that HDACs block MLP nuclear accumulation. Inhibition of heme oxygenase1 (HO-1) activity with protoporphyrin IX zinc(II) blocked MLP nuclear accumulation. To examine how mechanosensitivity changes during the transition to heart failure, we studied a guinea-pig model of angiotensin II infusion (400 ng kg(-1) min(-1) ) over 12 weeks. Using subcellular fractionation, we showed that the MLP ratio increased by 88% (n = 4, P < 0.01) during compensated hypertrophy but decreased significantly during heart failure (P < 0.001, n = 4). The MLP ratio correlated significantly with the E/A ratio (r = 0.71, P < 0.01, n = 12), a clinical measure of diastolic function. These data indicate for the first time that myocyte mechanosensitivity as indicated by the MLP ratio is regulated primarily by myocyte contractility via HO 1 and HDAC signalling. PMID- 26847745 TI - The value of molecular stratification for CEBPA(DM) and NPM1(MUT) FLT3(WT) genotypes in older patients with acute myeloid leukaemia. AB - Older adult patients (>=60 years) with acute myeloid leukaemia (AML) are generally considered to be poor-risk and there is limited information available regarding risk stratification based on molecular characterization in this age group, particularly for the double-mutant CEBPA (CEBPA(DM) ) genotype. To investigate whether a molecular favourable-risk genotype can be identified, we investigated CEBPA, NPM1 and FLT3 status and prognostic impact in a cohort of 301 patients aged 60 years or more with intermediate-risk cytogenetics, all treated intensively. Overall survival (OS) at 1 year was highest in the 12 patients (4%) that were CEBPA(DM) compared to the 76 (28%) with a mutant NPM1 and wild-type FLT3 (NPM1(MUT) FLT3(WT) ) genotype or all other patients (75%, 54%, 33% respectively), with median survival 15.2, 13.6 and 6.6 months, although the benefit was short-term (OS at 3 years 17%, 29%, 12% respectively). Combination of the CEBPA(DM) and NPM1(MUT) FLT3(WT) genotype patients defined a molecular group with favourable prognosis (P < 0.0001 in multivariate analysis), with 57% of patients alive at 1 year compared to 33% for all other patients. Knowledge of genotype in older cytogenetically intermediate-risk patients might influence therapy decisions. PMID- 26847746 TI - A survey of fertility and sexual health following allogeneic haematopoietic stem cell transplantation in New South Wales, Australia. AB - Four hundred and twenty-one adult allogeneic haematopoietic stem cell transplant (HSCT) survivors participated in a cross-sectional study to assess sexual dysfunction and infertility post-transplant. Survey instruments included the Sydney Post-Blood and Marrow Transplant (BMT) Survey, Functional Assessment of Cancer Treatment (FACT) - BMT, the Depression, Anxiety, Stress Scales (DASS 21), the Chronic Graft-versus-Host Disease (cGVHD) Activity Assessment- Patient Self Report (Form B), the Lee cGVHD Symptom Scale and The Post-Traumatic Growth Inventory. Most HSCT survivors reported sexual difficulties (51% of males; 66% of females). Men reported erectile dysfunction (79%) and decreased libido (61.6%) and women reported loss of libido (83%), painful intercourse (73%) and less enjoyment of sex (68%). Women also commonly reported vaginal dryness (73%), vaginal narrowing (34%) and vaginal irritation (26%). Woman had much higher rates of genital cGvHD than men (22% vs. 5%). Age and cGVHD were significantly associated with sexual dysfunction. Few survivors had children following transplant (3.3%). However, for those of reproductive age at HSCT, 22% reported trying to conceive, with 10.3% reporting success. This study is the largest to date exploring sexual function in survivors of allo-HSCT. This data provides the basis for health service reform to better meet the needs of HSCT survivors, including evidence to support counselling and education both pre- and post transplant. PMID- 26847747 TI - The Year in Cardiothoracic and Vascular Anesthesia: Selected Highlights From 2015. PMID- 26847748 TI - Evaluation of Persistent Organ Dysfunction Plus Death As a Novel Composite Outcome in Cardiac Surgical Patients. AB - OBJECTIVES: Validated composite outcomes after complicated cardiac surgery are poorly established. Therefore, the authors evaluated a novel composite endpoint, persistent organ dysfunction (POD)+death, which is defined as any need for life sustaining therapies or death at any time within 28 days from surgery. DESIGN: Secondary analysis extracted from a large-scale prospective randomized trial of critically ill cardiac surgery patients. SETTING: Multi-institutional, university hospitals. PARTICIPANTS: Ninety-five cardiac surgery patients with complicated postoperative courses. INTERVENTIONS: Cardiac surgery with cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS: At 28 days following surgery, the prevalence of POD was 15%, and 23% of patients had died (POD+death = 38%). Patients alive with POD at day 28 exhibited a significantly higher extent of organ injury and longer ICU (33 v 7 days; p<0.001) and hospital lengths of stay (49 v 21 days; p<0.001) compared to patients without POD at day 28. At 3 and 6 months, quality-of-life scores (by Short Form 36 questionnaire) showed a significantly reduced rating for most components in patients with POD at day 28 compared to those without POD. The 6-month mortality rate was 21% among patients alive with POD at day 28 compared to 5% among patients alive without POD (p = 0.05). The calculated number of patients needed per arm to detect a 25% relative risk reduction for mortality alone was 762 compared to 386 per arm for POD+ death. CONCLUSIONS: POD+death at day 28 following cardiac surgery may be a valid composite endpoint and offers statistical efficiencies in terms of sample size calculations for cardiac surgical trials. PMID- 26847749 TI - Liver Transplantation: Intraoperative Transesophageal Echocardiography Findings and Relationship to Major Postoperative Adverse Cardiac Events. AB - OBJECTIVE: The primary aim of the study was to describe the most common intraoperative transesophageal echocardiography (TEE) findings during the 3 separate phases of orthotopic liver transplantation (OLT). The secondary aim of the study was to determine if the abnormal TEE findings were associated with major postoperative adverse cardiac events (MACE) and thus may be amenable to future management strategies. DESIGN: Data were collected retrospectively from the electronic medical record and institutional echocardiography database. SETTING: Single university hospital. PARTICIPANTS: A total of 100 patients undergoing OLT via total cavaplasty technique. INTERVENTIONS: Intraoperative TEE was performed in all 3 phases of OLT. MEASUREMENT AND MAIN RESULTS: TEE findings of 100 patients who had TEE during OLT during the dissection, anhepatic, and reperfusion phases of transplantation were recorded after blind review. Findings then were analyzed to see if those findings were predictive of postoperative MACE. Intraoperative TEE findings varied among the different phases of OLT. Common TEE findings at reperfusion were microemboli (n = 40, 40%), isolated right ventricular dysfunction (n = 22, 22%), and intracardiac thromboemboli (n = 20, 20%). CONCLUSIONS: Intraoperative echocardiography findings during liver transplantation varied during each phase of transplantation. The presence of intracardiac thromboemboli or biventricular dysfunction on intraoperative echocardiography was predictive of short- and long-term major postoperative adverse cardiac events. PMID- 26847750 TI - Assessment of Coronary Blood Flow by Transesophageal Echocardiography. PMID- 26847751 TI - Drawing Inferences From Transesophageal Echocardiography. PMID- 26847752 TI - Reply to Letter From Sebastian J. Baxter and Siax I. Jaggar Entitled, "Teicoplanin, Acute Kidney Injury and Surgical-Site Infection in Cardiac Surgery". PMID- 26847753 TI - Teicoplanin, Acute Kidney Injury and Surgical-Site Infection in Cardiac Surgery. PMID- 26847754 TI - Reply: Acute Kidney Injury Definition and Beyond. PMID- 26847755 TI - In Response to: Calculating the Protamine Dose Necessary to Neutralize Heparin in All Patients Under All Circumstances by Jan R de Jong and Christa Boer. PMID- 26847756 TI - Esmolol Added in Repeated Cold Oxygenated Blood Cardioplegia Improves Myocardial Function After Cardiopulmonary Bypass. PMID- 26847757 TI - Reply: Esmolol Added in Cardioplegia. PMID- 26847759 TI - The ontogeny of great ape gesture - not a simple story: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26847760 TI - A modality-independent, neurobiological grounding for the combinatory capacity of the language-ready brain: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26847758 TI - Role of multiparametric magnetic resonance imaging in early detection of prostate cancer. AB - Most prostate cancers (PC) are currently found on the basis of an elevated PSA, although this biomarker has only moderate accuracy. Histological confirmation is traditionally obtained by random transrectal ultrasound guided biopsy, but this approach may underestimate PC. It is generally accepted that a clinically significant PC requires treatment, but in case of an non-significant PC, deferment of treatment and inclusion in an active surveillance program is a valid option. The implementation of multiparametric magnetic resonance imaging (mpMRI) into a screening program may reduce the risk of overdetection of non-significant PC and improve the early detection of clinically significant PC. A mpMRI consists of T2-weighted images supplemented with diffusion-weighted imaging, dynamic contrast enhanced imaging, and/or magnetic resonance spectroscopic imaging and is preferably performed and reported according to the uniform quality standards of the Prostate Imaging Reporting and Data System (PIRADS). International guidelines currently recommend mpMRI in patients with persistently rising PSA and previous negative biopsies, but mpMRI may also be used before first biopsy to improve the biopsy yield by targeting suspicious lesions or to assist in the selection of low risk patients in whom consideration could be given for surveillance. TEACHING POINTS: * MpMRI may be used to detect or exclude significant prostate cancer. * MpMRI can guide targeted rebiopsy in patients with previous negative biopsies. * In patients with negative mpMRI consideration could be given for surveillance. * MpMRI may add valuable information for the optimal treatment selection. PMID- 26847761 TI - On the role of emerging voluntary control of vocalization in language evolution: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26847762 TI - Ready..., Set, Go!: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26847763 TI - To move as a human: Comment on "The embodiment of assistive devices-from wheelchair to exoskeleton" by M. Pazzaglia and M. Molinari. PMID- 26847764 TI - Comment to "One-stop endoscopic hernia surgery: efficient and satisfactory" Voorbrood et al. Hernia 19:395-400. PMID- 26847766 TI - Macrospin dynamics in antiferromagnets triggered by sub-20 femtosecond injection of nanomagnons. AB - The understanding of how the sub-nanoscale exchange interaction evolves in macroscale correlations and ordered phases of matter, such as magnetism and superconductivity, requires to bridging the quantum and classical worlds. This monumental challenge has so far only been achieved for systems close to their thermodynamical equilibrium. Here we follow in real time the ultrafast dynamics of the macroscale magnetic order parameter in the Heisenberg antiferromagnet KNiF3 triggered by the impulsive optical generation of spin excitations with the shortest possible nanometre wavelength and femtosecond period. Our magneto optical pump-probe experiments also demonstrate the coherent manipulation of the phase and amplitude of these femtosecond nanomagnons, whose frequencies are defined by the exchange energy. These findings open up opportunities for fundamental research on the role of short-wavelength spin excitations in magnetism and strongly correlated materials; they also suggest that nanospintronics and nanomagnonics can employ coherently controllable spin waves with frequencies in the 20 THz domain. PMID- 26847765 TI - Polyhydramnios in Lrp4 knockout mice with bilateral kidney agenesis: Defects in the pathways of amniotic fluid clearance. AB - Amniotic fluid volume during mid-to-late gestation depends mainly on the urine excretion from the foetal kidneys and partly on the fluid secretion from the foetal lungs during foetal breathing-like movements. Urine is necessary for foetal breathing-like movements, which is critical for foetal lung development. Bilateral renal agenesis and/or obstruction of the urinary tract lead to oligohydramnios, which causes infant death within a short period after birth due to pulmonary hypoplasia. Lrp4, which functions as an agrin receptor, is essential for the formation of neuromuscular junctions. Herein, we report novel phenotypes of Lrp4 knockout (Lrp4(-/-)) mice. Most Lrp4(-/-) foetuses showed unilateral or bilateral kidney agenesis, and Lrp4 knockout resulted in polyhydramnios. The loss of Lrp4 compromised foetal swallowing and breathing-like movements and downregulated the expression of aquaporin-9 in the foetal membrane and aquaporin 1 in the placenta, which possibly affected the amniotic fluid clearance. These results suggest that amniotic fluid removal was compromised in Lrp4(-/-) foetuses, resulting in polyhydramnios despite the impairment of urine production. Our findings indicate that amniotic fluid removal plays an essential role in regulating the amniotic fluid volume. PMID- 26847767 TI - [The long road from molecular biology to clinical practice in colorectal cancer]. PMID- 26847768 TI - From competency to dormancy: a 3D model to study cancer cells and drug responsiveness. AB - BACKGROUND: The heterogeneous and dynamic tumor microenvironment has significant impact on cancer cell proliferation, invasion, drug response, and is probably associated with entering dormancy and recurrence. However, these complex settings are hard to recapitulate in vitro. METHODS: In this study, we mimic different restriction forces that tumor cells are exposed to using a physiologically relevant 3D model with tunable mechanical stiffness. RESULTS: Breast cancer MDA MB-231, colon cancer HCT-116 and pancreatic cancer CFPAC cells embedded in the stiffer gels exhibit a changed morphology and cluster formation, prolonged doubling time, and a slower metabolism rate, recapitulating the pathway from competency to dormancy. Altering environmental restriction allows them to re enter and exit dormant conditions and change their sensitivities to drugs such as paclitaxol and gemcitabine. Cells surviving drug treatments can still regain competent growth and form tumors in vivo. CONCLUSION: We have successfully developed an in vitro 3D model to mimic the effects of matrix restriction on tumor cells and this high throughput model can be used to study tumor cellular functions and their drug responses in their different states. This all in one platform may aid effective drug development. PMID- 26847770 TI - WHO analgesic ladder and chronic pain: the need to search for treatable causes. PMID- 26847769 TI - The anterior chamber of the eye is a transplantation site that supports and enables visualisation of beta cell development in mice. AB - AIMS/HYPOTHESIS: In vivo imaging of the developing pancreas is challenging due to the inaccessibility of the tissue. To circumvent this, on embryonic day 10.5 (E10.5) we transplanted a mouse developing pancreatic bud into the anterior chamber of the eye (ACE) to determine whether the eye is a useful transplant site to support pancreas development. METHODS: We transplanted an E10.5 dorsal pancreatic bud into the ACE of a syngeneic recipient mouse. Using a mouse insulin promoter-green fluorescent protein (MIP-GFP) mouse as the tissue donor, we non invasively imaged the pancreatic bud as it develops at single beta cell resolution across time. RESULTS: The transplanted pancreatic bud rapidly engrafts and vascularises when transplanted into the ACE. The pancreatic progenitor cells differentiate into exocrine and endocrine cells, including cells expressing insulin, glucagon and somatostatin. The morphology of the transplanted pancreatic bud resembles that of the native developing pancreas. Beta cells within the transplanted pancreatic bud respond to glucose in a manner similar to that of native fetal beta cells and superior to that of in vitro developed beta cells. Unlike in vitro grown pancreatic explants, pancreatic tissue developing in the ACE is vascularised, providing the developing pancreatic tissue with a milieu resembling the native situation. CONCLUSIONS/INTERPRETATION: Altogether, we show that the ACE is able to support growth, differentiation and function of a developing pancreatic bud across time in vivo. PMID- 26847771 TI - Vaccinations, response, and controls before and after intestinal transplantation in children. AB - Vaccination is an effective strategy to decrease infections in transplant recipients. Children after intestinal transplantation carry a high risk of infection due to increased immunosuppression. In a series of 22 children after intestinal transplantation, we studied the vaccination schedules and the antibodies against vaccine-preventable diseases before transplantation, and at one and five yr after transplantation. We reviewed whether the vaccination schedules were complete, and we analysed the factors that may influence serological immunity and the incidence of disease in patients with deficient immunity. All patients completed the recommended vaccination schedules for DTaP IPV and HBV. After transplantation, the negative antibodies against vaccine preventable diseases were mostly related to an antirejection therapy: for DTaP IPV: four of four patients with no antibody had been treated for rejection, for HBV: two of five, HAV: three of four, MMR: three of seven, and VZV: three of four. A post-transplantation varicella infection was followed by acute rejection, with probability for a relationship between both events. We observed 50% of varicella cases in unvaccinated children, highlighting the importance of pretransplant vaccination. Waning immunogenicity mediated by antibodies against vaccine-preventable disease after transplantation indicated a need for boosters. The recommendations should be regularly enforced, as the reliance on routine immunizations schedules is not adequate in immunocompromised patients. PMID- 26847772 TI - Adrenomedullin in the growth modulation and differentiation of acute myeloid leukemia cells. AB - Adrenomedullin (ADM) is a regulatory peptide endowed with multiple biological effects, including the regulation of blood pressure, cell growth and innate host defence. In the present study, we demonstrated that ADM signaling could be involved in the impaired cellular differentiation of myeloid leukemia cells to mature granulocytes or monocytes by modulating RAMPs/CRLR expression, PI3K/Akt cascade and the ERK/MAPK signaling pathway. When exogenously administered to in vitro cultures of HL60 promyelocytic leukemia cells, ADM was shown to exert a strong proliferative effect with minimal upregulation in the expression level of monocyte antigen CD14. Notably, the experimental inhibition of ADM signaling with inhibitor ADM22-52 promoted a differentiative stimulation towards monocytic and granulocytic lineages. Moreover, based on the expression of CD31 relative to CD38, we hypothesized that an excess of ADM in bone marrow (BM) niche could increase the transendothelial migration of leukemia cells while any inhibitory event of ADM activity could raise cell retention in hyaluronate matrix by upregulating CD38. Taken into consideration the above evidence, we concluded that ADM and ADM22-52 could differently affect the growth of leukemia cells by autocrine/paracrine mechanisms and may have clinical relevance as biological targets for the intervention of tumor progression. PMID- 26847774 TI - Just Let Kids be Kids. PMID- 26847773 TI - Hepatic Transporter Expression in Metabolic Syndrome: Phenotype, Serum Metabolic Hormones, and Transcription Factor Expression. AB - Metabolic syndrome is a multifactorial disease associated with obesity, insulin resistance, diabetes, and the alteration of multiple metabolic hormones. Obesity rates have been rising worldwide, which increases our need to understand how this population will respond to drugs and exposure to other chemicals. The purpose of this study was to determine in lean and obese mice the ontogeny of clinical biomarkers such as serum hormone and blood glucose levels as well as the physiologic markers that correlate with nuclear receptor- and transporter-related pathways. Livers from male and female wild-type (WT) (C57BL/6) and ob/ob mice littermates were collected before, during, and after the onset of obesity. Serum hormone and mRNA levels were analyzed. Physiologic changes and gene expression during maturation and progression to obesity were performed and correlation analysis was performed using canonical correlations. Significant ontogenic changes in both WT and ob/ob mice were observed and these ontogenic changes differ in ob/ob mice with the development of obesity. In males and females, the ontogenic pattern of the expression of genes such as Abcc3, 4, Abcg2, Cyp2b10, and 4a14 started to differ from week 3, and became significant at weeks 4 and 8 in ob/ob mice compared with WT mice. In obese males, serum resistin, glucagon, and glucose levels correlated with the expression of most hepatic ATP-binding cassette (Abc) transporters, whereas in obese females, serum glucagon-like peptide 1 levels were correlated with most hepatic uptake transporters and P450 enzymes. Overall, the correlation between physiologic changes and gene expression indicate that metabolism-related hormones may play a role in regulating the genes involved in drug metabolism and transport. PMID- 26847775 TI - An Introduction to the Smart Tots Consensus Statement on the Use of Anesthetic and Sedative Drugs in Infants and Toddlers. PMID- 26847776 TI - Perioperative Adverse Respiratory Events in Overweight/Obese Children: Systematic Review. AB - Childhood obesity is associated with numerous respiratory disorders, which may be aggravated when general anesthesia is administered. This systematic review aimed to investigate and synthesize the published literature on the associations between childhood obesity and perioperative adverse respiratory events (PAREs). By using key terms, observational studies published between 1990 and 2014 in English-language journals indexed by Cumulative Index for Nursing and Allied Health Literature, PubMed, Web of Science, Cochrane Database, and EMBASE were searched for reports of relevant associations. Nine articles were considered eligible for inclusion. In all studies, significant univariate and multivariate associations were reported between obesity and increased risk for PAREs in pediatric patients, mainly for hypoxemia, upper airway obstruction, and difficult mask ventilation. Appropriate strategies for preventing PAREs in obese children need to be followed by health care professionals. Multicenter studies are also recommended for ensuring high generalizability of reported associations and elucidating underlying mechanisms that link obesity to PAREs. PMID- 26847777 TI - Integrative Literature Review: Ascertaining Discharge Readiness for Pediatrics After Anesthesia. AB - PURPOSE: Unplanned hospital readmissions after the administration of general anesthesia for ambulatory procedures may contribute to loss of reimbursement and assessment of financial penalties. Pediatric patients represent a unique anesthetic risk. The purpose of this integrative literature review was to ascertain specific criteria used to evaluate discharge readiness for pediatric patients after anesthesia. DESIGN: This study is an integrative review of literature. METHODS: An integrative literature search was conducted and included literature sources dated January 2008 to November 2013. Key words included pediatric, anesthesia, discharge, criteria, standards, assessment, recovery, postoperative, postanesthesia, scale, score, outpatient, and ambulatory. FINDING: Eleven literature sources that contributed significantly to the research question were identified. Levels of evidence included three systematic reviews, one randomized controlled trial, three cohort studies, two case series, and two expert opinions. CONCLUSIONS AND IMPLICATIONS: This integrative literature review revealed evidence-based discharge criteria endorsing home readiness for postanesthesia pediatric patients should incorporate consideration for physiological baselines, professional judgment with regard to infant consciousness, and professional practice standards/guidelines. Additionally, identifying and ensuring discharge to a competent adult was considered imperative. Nurses should be aware that frequently used anesthesia scoring systems originated in the 1970s, and this review was unable to locate current literature examining the reliability and validity of their use in conjunction with modern anesthesia-related health care practices. PMID- 26847778 TI - Demographic Predictors of NPO Violations in Elective Pediatric Surgery. AB - PURPOSE: The parents of pediatric patients are routinely instructed to abstain from food and liquids before elective surgeries. Our objectives were to determine if demographic factors were associated with fasting violations and to identify reasons for noncompliance. DESIGN: This was a matched case-control pilot study. METHODS: A total of 63 patients who violated fasting guidelines were identified and matched to three controls within the same surgical service. Demographic and clinical variables were evaluated as predictors of noncompliance in a multivariate regression model. Qualitative data were coded into the most commonly identified reasons for non per os (Latin)-nothing by mouth violations. FINDINGS: Parents of children who did not comply commonly reported that they did not receive or did not understand the fasting guidelines. Noncompliant patients were significantly more likely to experience surgical delays and cancellations. None of the demographic and clinical variables assessed were significantly associated with non per os (Latin)-nothing by mouth violations in this pilot study. CONCLUSIONS: Quality improvement actions may be necessary to ensure that parents receive and understand fasting guidelines for their children. This might include use of teach-back methods, modification of instructional materials, or providing follow-up information after the initial encounter. PMID- 26847779 TI - High Risk of Postoperative Urinary Retention in 1-Year-Old Cleft Palate Patients: An Observational Study. AB - PURPOSE: Estimate the frequency of urinary catheterizations in a high-risk population of children. DESIGN: It was a descriptive, observational study. METHODS: Incidence of postoperative urinary retention was recorded for one-year old cleft palate surgery patients admitted to the postanaesthesia care unit or pediatric intensive care unit at Rikshospitalet, Oslo University Hospital, Norway. FINDING: Forty-five out of 70 patients (64%) were catheterized once or several times during the perioperative period. Furthermore, a total of 40 out of 54 patients (74%) had a bladder volume 60 mL or more measured by ultrasound scanner; 10 of these measured volumes exceeded twice the bladder capacity. CONCLUSIONS: Postoperative urinary retention was discovered in 64% of patients; some of them were catheterized more than once during the perioperative period. Based on these data and the departmental procedure for postoperative care of these patients, the results indicated the need for an indwelling catheter. PMID- 26847780 TI - Nursing Activities in the Prevention and Treatment of Perioperative Complications After Airway Foreign Body Removal in Pediatric Patients. AB - PURPOSE: 1) To evaluate postanesthesia complications after bronchoscopy performed for a suspected foreign body (FB) in the pediatric population and 2) To propose an algorithm of nursing activities for management of this problem. DESIGN: A retrospective descriptive design was used. METHODS: A chart review of 155 children who underwent rigid bronchoscopy for FB removal was conducted. FINDING: Complications occurred in 78% of children: 43% of them experienced desaturation below 90% requiring oxygen therapy. Therapy ranged from oxygen administration via blow-by nasal cannula or face mask (89%) to positive pressure ventilation via bag mask (23%). Seven percent of the population required intubation and admission to intensive care unit (all were less than 2 years of age). CONCLUSIONS: Our results suggest special attention to the children less than 2 years of age as serious respiratory failure may occur after FB removal. The algorithm for nurses was created to manage children after bronchoscopy. PMID- 26847781 TI - The Effects of Distraction on Preoperative Anxiety Level in Children. AB - PURPOSE: The purpose of this study was to investigate the effects of distraction on the preoperative anxiety levels of pediatric patients. DESIGN: A prospective, two-group experimental design was used. METHODS: This study was conducted in the clinic of pediatric surgery of a university hospital in Turkey between November 20, 2013 and January 25, 2014. The population of the study was composed of a total of 83 children (40 in the study group and 43 in the control group) who met the inclusion. The data were collected using the "Personal Information Form," "Separation Scoring," and "State-Trait Anxiety Inventory for Children-State Form." Distraction was performed on the children in the study group during the preoperative period. No intervention was applied to the children in the control group. FINDING: The results of this study demonstrated that the separation scores and State-Trait Anxiety Inventory for Children-State scores of the children in the study group, on whom distraction was applied, were lower than those of the control group. CONCLUSIONS: Distraction applied to children in the preoperative period significantly reduced anxiety and separation anxiety. PMID- 26847782 TI - Structured Handover in the Pediatric Postanesthesia Care Unit. AB - PURPOSE: To establish a structured handover in the pediatric postanesthesia care unit. DESIGN: An observational prequality and postquality improvement design was used. METHODS: Convenience samples of 52 preimplementation and 51 postimplementation handover interactions (N = 103) were observed and compared to a 42-item Introductions, Situation, Background, Assessment, Recommendations, & Questions checklist. Patient care team members' satisfaction was assessed using voluntary electronic surveys. Data were analyzed for descriptive measures and differences in the pre- and postchecklist, and satisfaction total scores were compared using a two-sample t test. FINDING: The implementation of the handover checklist resulted in a statistically significant increase in the percentage of items discussed during five of six handover phases (P < .001). Overall, a significant increase in provider satisfaction was demonstrated from preimplementation to postimplementation (P < .01). The average duration of handover (in minutes) was not significantly different from pre (mean = 5.80 +/- 3.80) to post (mean = 6.80 +/- 2.30), P = .15. CONCLUSIONS: A structured handover checklist is associated with increased communication of handover content information and improved provider satisfaction. No statistically significant effect on handover duration time was found. PMID- 26847783 TI - Development of a Formalized Pediatric Visitation Program in the PACU Through Evidence-Based Practice. AB - IDENTIFICATION OF THE PROBLEM: The national trend and 2003 American Society of PeriAnesthesia Nurses position statement supports visitation during Phase I care. Nurses at our institution had an inconsistent practice of rejoining families with their child during this period. PURPOSE: The purpose of this project was to investigate nurses' attitudes and beliefs toward family-centered care. A formalized pediatric visitation program was also created. METHODOLOGY: A survey was used to evaluate nurses' attitudes and beliefs regarding family-centered care. Education was provided for the nurses and patient and/or families. The formalized visitation program included updated policies, use of technological support to improve communication with families, and development of an educational pamphlet. OUTCOMES: A pediatric visitation program that reunites the family and child while supporting nurses was developed and implemented. IMPLICATIONS FOR PERIANESTHESIA NURSES: This visitation program may be explored for replication in perianesthesia or other applicable settings. PMID- 26847784 TI - Addressing the Barriers to Pain Management in Ambulatory Surgery. PMID- 26847785 TI - Pulse Oximetry for Perioperative Monitoring. PMID- 26847787 TI - The International Collaboration of PeriAnesthesia Nurses Is Born. PMID- 26847786 TI - Battling Supply Waste in the ICU: A Bedside Cart Standardization Project. PMID- 26847788 TI - Nurse Engagement in Health Care Information Technology Policy. PMID- 26847789 TI - Research News: Obstructive Sleep Apnea in Children. PMID- 26847790 TI - Reflections of Professional Generosity: Leaving a Legacy. PMID- 26847791 TI - A 3-D cell culture system to study epithelia functions using microcarriers. AB - In vitro cell culture models used to study epithelia and epithelial diseases would benefit from the recognition that organs and tissues function in a three dimensional (3D) environment. This context is necessary for the development of cultures that more realistically resemble in vivo tissues/organs. Our aim was to establish and characterize biologically meaningful 3D models of epithelium. We engineered 3D epithelia cultures using a kidney epithelia cell line (MDCK) and spherical polymer scaffolds. These kidney epithelia were characterized by live microscopy, immunohistochemistry and transmission electron microscopy. Strikingly, the epithelial cells displayed increased physiological relevance; they were extensively polarized and developed a more differentiated phenotype. Using such a growth system allows for direct transmission and fluorescence imaging with few restrictions using wide-field, confocal and Light Sheet Fluorescence Microscopy. We also assessed the wider relevance of this 3D culturing technique with several epithelial cell lines. Finally, we established that these 3D micro-tissues can be used for infection as well as biochemical assays and to study important cellular processes such as epithelial mesenchymal transmission. This new biomimetic model could provide a broadly applicable 3D culture system to study epithelia and epithelia related disorders. PMID- 26847792 TI - Fine Mapping Identifies a New QTL for Brown Rice Rate in Rice (Oryza Sativa L.). AB - BACKGROUND: High yield and quality determine the commercial potential of rice variety. Brown rice rate (BRR) is a key factor ensuring grain yield and quality in rice. So far, there were few reports about the genes that directly controlled the BRR in rice. Therefore, dissecting the genetic mechanism of the BRR genes can facilitate improving effective rice supply or edible grain yield. RESULTS: A double haploid population derived from the cross between Taichung Native 1 (TN1) (an indica variety) and Chunjiang 06 (CJ06) (a japonica variety) was used to investigate the genetic basis of grain milling and appearance traits affecting the BRR. By using a constructed molecular linkage map, four quantitative trait loci (QTLs) for the BRR were detected on chromosomes 1, 8, 9, and 10, respectively. In addition, three QTLs for appearance traits, including grain weight and grain length/width ratio, were detected on chromosomes 6, 9 and 10, respectively. Chromosome segment substitution lines (CSSLs) were established at the qBRR-10 locus. Finally, the qBRR-10 was narrowed to a 39.5 kb region on chromosome 10. In this region, two candidate genes, LOC_Os10g32124 and LOC_Os10g32190, showed significantly differential expression in TN1 and CSSL1-2 compared with CJ06. Histocytological analysis suggested that cell size and hull thickness may be important factors for the BRR. CONCLUSION: In the study, the qBRR-10 affected the BRR and was finally located to a region between two markers, P13 and P14. Two candidate genes were selected based on the expression difference between two parents, which facilitated the further cloning of the qBRR-10 gene and largely contributed to improve the grain yield and quality in rice. PMID- 26847793 TI - Genomic analysis of the nitrate-respiring Sphingopyxis granuli (formerly Sphingomonas macrogoltabida) strain TFA. AB - BACKGROUND: Sphingomonads are Alphaproteobacteria that belong to the Sphingomonas, Novosphingobium, Sphingopyxis or Sphingobium genera, They are physiologically diverse and broadly distributed in nature, playing important roles in oligotrophic environments and in the degradation of recalcitrant polyaromatic compounds, Sphingopyxis is a poorly studied genus of which only one representative (S. alaskensis RB2256) has been deeply characterized. In this paper we analyze the genomic features of S. granuli strain TFA (formerly Sphingomonas macrogoltabida) in comparison with the available Sphingopyxis sequenced genomes, to describe common characteristics of this genus and to highlight unique characteristics of strain TFA. RESULTS: The TFA genome has been assembled in a single circular chromosome of 4.7 Mb. Genomic sequence analysis and proteome comparison re-assigned the TFA strain to the Sphingopyxis genus and the S. granuli species. Some regions of the TFA genome show high similarity (ca. 100%) to other bacteria and several genomic islands have been detected. Pathways for aromatic compound degradation have been predicted but no growth of TFA has been detected using these as carbon or nitrogen sources. Genes for nitrate respiration have been identified as TFA exclusive. Experimental data on anaerobic growth of TFA using nitrate as a terminal electron acceptor are also provided. CONCLUSIONS: Sphingopyxis representatives form a compact phylogenetic group (with the exception of S. baekryungensis DSM 16222) that share several characteristics, such as being naturally resistant to streptomycin, having only one ribosomal operon, a low number of prophages and CRISPR sequences, absence of selenoproteins and presence of ectoin and other biosynthesis pathways for secondary metabolites. Moreover, the TFA genome organization shows evidence of the presence of putative integrative and conjugative elements (ICE) responsible for the acquisition of several characteristics by horizontal transfer mechanisms. Sphingopyxis representatives have been described as strict aerobes but anaerobic growth using nitrate as a terminal electron acceptor might confer an environmental advantage to the first S. granuli strain characterized at genomic level. PMID- 26847794 TI - Complexes of trophoblastic peptides and heat shock protein 70 as a novel contraceptive vaccine in a mouse model. AB - The concept of contraceptive vaccines has interested reproductive biologists and immunologists for nearly 2 decades, but no approach has been approved. In this study, a new immunocontraceptive vaccine that targets placental trophoblasts was expored. We demonstrated that after in-vitro binding with heat shock protein 70, trophoblast-derived peptides can activate T cells both in vitro and in vivo. The activated T cells have a Th1 bias and specifically cause cytolysis of trophoblasts, leading to the termination of pregnancy. Such activated T cells seem to have an effect on early gestation, rather than influencing preimplantation. We did not observe side-effects of this vaccine in mice. In conclusion, a novel contraceptive strategy is described that uses heat shock protein 70-trophoblastic peptide complexes to generate a specific T-cell immune response against placental trophoblasts. This type of vaccine targeting the post implantation phase does not generate a permanent effect but possibly raises an ethical issue. PMID- 26847795 TI - Alfentanil anesthetic augmentation lengthens seizure duration in electroconvulsive therapy with older people. AB - Electroconvulsive therapy (ECT) prescription rates rise with age, making it important that treatments be made as effective and safe as possible (Plakiotis et al., 2012). Older people are vulnerable to post-treatment confusion and to subsequent deficits in attention, new learning, and autobiographical memory (Gardner and O'Connor, 2008). Strategies to minimize cognitive side-effects include unilateral electrode placement and stimulus dose titration whereby electrical charge is individually calibrated to seizure threshold (Sackeim et al., 2000). It remains the case, however, that threshold levels typically rise over the treatment course, leading to an increase both in delivered charge and the risk of adverse sequelae. PMID- 26847796 TI - Systematic review of evidence and consensus on perianal fistula: an analysis of national and international guidelines. AB - AIM: Treatment of perianal fistula has evolved with the introduction of new techniques and biologicals in Crohn's disease (CD). Several guidelines are available worldwide, but many recommendations are controversial or lack high quality evidence. The aim of this work was to provide an overview of the current available national and international guidelines for perianal fistula and to analyse areas of consensus and areas of conflicting recommendations, thereby identifying topics and questions for future research. METHOD: MEDLINE, EMBASE and PubMed were systematically searched for guidelines on perianal fistula. Inclusion was limited to papers in English less than 10 years old. The included topics were classified as having consensus (unanimous recommendations in at least two-thirds of the guidelines) or controversy (fewer than three guidelines commenting on the topic or no consensus) between guidelines. The highest level of evidence was scored as sufficient (level 3a or higher of the Oxford Centre for Evidence-based Medicine Levels of Evidence 2009, http://www.cebm.net/oxford-centre-evidence based-medicine-levels-evidence-march-2009/) or insufficient. RESULTS: Twelve guidelines were included and topics with recommendations were compared. Overall, consensus was present in 15 topics, whereas six topics were rated as controversial. Evidence levels varied from strong to lack of evidence. CONCLUSION: Evidence on the diagnosis and treatment of perianal fistulae (cryptoglandular or related to CD) ranged from nonexistent to strong, regardless of consensus. The most relevant research questions were identified and proposed as topics for future research. PMID- 26847797 TI - Differential ontogenetic exposure to obesogenic environment induces hyperproliferative status and nuclear receptors imbalance in the rat prostate at adulthood. AB - BACKGROUND: Experimental data indicate that high-fat diet (HFD) may alter proliferative activity and prostate health. However, the consequences of HFD exposure during different periods of ontogenetic development on prostate histophysiology remain to be elucidated. Herein, we compare the influence of obesogenic environment (OE) due to maternal obesity and HFD at different periods of life on proliferative activity and nuclear receptors frequency in the rat ventral prostate and a possible relationship with metabolic and hormonal alterations. METHODS: Male Wistar rats (19 weeks old), treated with balanced chow (Control group-C; 3% high-fat, 3.5 Kcal/g), were compared with those exposed to HFD (20% high-fat, 4.9 kcal/g) during gestation (G-maternal obesity), gestation and lactation (GL), from post-weaning to adulthood (WA), from lactation to adulthood (LA) and from gestation to adulthood (GA). After the experimental period, the ventral prostate lobes were removed and analyzed with different methods. RESULTS: Metabolic data indicated that G and GL rats became insulin resistant and WA, LA, and GA became insulin resistant and obese. There was a strong inverse correlation between serum testosterone (~133% lower) and leptin levels (~467% higher) in WA, LA, and GA groups. Estrogen serum levels increased in GA, and insulin levels increased in all groups, especially in WA (64.8*). OE groups exhibited prostatic hypertrophy, since prostate weight increased ~40% in G, GL, LA, and GA and 31% in WA. As indicated by immunohistochemistry, all HFD groups except G exhibited an increase in epithelial cell proliferation (PCNA positive) and a decrease in frequency of AR- and ERbeta-positive epithelial cells; there was also an increment of ERalpha-positive stromal cells in comparison with control. Cells containing PPARgamma increased in both epithelium and stroma of all OE groups and those expressing LXRalpha decreased, particularly in groups OE-exposed during gestation (G, GL and GA). CONCLUSIONS: OE leads to prostate hypertrophy regardless of the period of development and, except when restricted to gestation, leads to a hyperproliferative status which was correlated to downregulation of AR and LXRalpha and upregulation of ERalpha and PPARgamma signaling. PMID- 26847798 TI - A novel LC-MS/MS assay for heparan sulfate screening in the cerebrospinal fluid of mucopolysaccharidosis IIIA patients. AB - AIMS: Heparan sulfate (HS) accumulates in the central nervous system in mucopolysaccharidosis III type A (MPS IIIA). A validated LC-MS/MS assay was developed to measure HS in human cerebrospinal fluid (CSF). METHODS & RESULTS: HS was extracted and digested and the resultant disaccharides were derivatized with a novel label, 4-butylaniline, enabling isoform separation and isotope-tagged analog introduction as an internal standard for LC-MS/MS. The assay has a LLOQ for disaccharides of 0.1 MUM, +/-20% accuracy and <=20% precision. CSF samples from patients with MPS IIIA showed elevated HS levels (mean 4.9 MUM) compared with negative controls (0.37 MUM). CONCLUSION: This assay detected elevated HS levels in the CSF of patients with MPS IIIA and provides a method to assess experimental therapies. PMID- 26847800 TI - Corrigendum. PMID- 26847799 TI - Experimental testing of the dual-layer Woven EndoBridge device using an elastase induced aneurysm model in rabbits. AB - The dual-layer Woven EndoBridge (WEB) device (WEB II) is designed to improve the performance of the first-generation WEB device. This study was performed to evaluate the acute and chronic performance of WEB II for aneurysm occlusion in an elastase-induced aneurysm model in rabbits. We implanted WEB II devices in 36 elastase-induced aneurysms and followed up for one, three, six, and 12 months. Degree of aneurysm occlusion at follow-up was graded on the Web Occlusion Scale (WOS): Grade A, complete aneurysm occlusion; Grade B, complete occlusion with recess filling; Grade C, residual neck filling; and Grade D, residual aneurysm filling. Hematoxylin and eosin staining was performed for histological assessment of aneurysm healing. Grades A, B, C, and D aneurysm occlusion at one-month follow up were noted in three (17%), three (17%), eight (44%), and four (22%) of 18 cases, respectively. At the three-month time point Grades A, B, C, and D were shown in two (33%), two (33%), one (17%), and one (17%) aneurysms. Six months after treatment, one (17%), two (33%), two (33%), and one (17%) cases demonstrated Grades A, B, C, and D occlusion. At the 12-month time point, Grades B, C, and D were shown in three (50%), two (33%), and one (17%) aneurysms. Histologic evaluation showed progressive thrombus organization within aneurysm lumen from one to 12 months. These results indicated that the WEB II device can achieve high rates of aneurysm occlusion over time in experimental aneurysms. PMID- 26847801 TI - Emergency Incident Rehabilitation: Resource Document to the Position Statement of the National Association of EMS Physicians. AB - Position Statement: Emergency Incident Rehabilitation The National Association of EMS Physicians(r) believes that: Emergency operations and training conducted while wearing protective clothing and respirators is physiologically and cognitively demanding. The heat stress and fatigue created by working in protective clothing and respirators creates additional risk of illness/injury for the public safety provider. Emergency incident rehabilitation provides a structured rest period for rehydration and correction of abnormal body core temperature following work in protective clothing and respirators. Emergency incident rehab should be conducted at incidents (e.g. fireground, hazardous materials, and heavy rescue emergencies) and trainings involving activities that may lead to exceeding safe levels of physical and mental exertion. Emergency incident rehabilitation is incident care, not fitness for duty, and meant to reduce physiologic strain and prepare the responder to return to duty at the current incident and for the remainder of the shift. EMS should play a role in emergency incident rehabilitation with providers trained to understand the physiologic response of healthy individuals to environmental, exertional, and cognitive stress and implement appropriate mitigation strategies. An appropriately qualified physician should have oversight over the creation and implementation of emergency incident rehabilitation protocols and may be separate from the roles and responsibilities of the occupational medicine physician. There are no peer-reviewed data related to cold weather rehabilitation. Future studies should address this limitation to the literature. PMID- 26847802 TI - Bioartificial liver attenuates intestinal mucosa injury and gut barrier dysfunction after major hepatectomy: Study in a porcine model. AB - BACKGROUND: The aim of this study was to evaluate whether bioartificial liver support can attenuate gut mucosa injury in a porcine model of posthepatectomy liver dysfunction. METHODS: Posthepatectomy liver failure was induced in pigs combining major (70%) liver resection and ischemia/reperfusion injury. An ischemic period of 150 minutes was followed by reperfusion for 24 hours. Animals were divided randomly into 2 groups: a control group (n = 6) that received standard critical care and a bioartificial liver support group (Hepat, n = 6) that were subjected to extracorporeal liver support for 6 hours during reperfusion. Intestinal mucosal injury, bacterial translocation, and endotoxin translocation were evaluated in all animals. Intestinal mucosa was also evaluated with markers of oxidative injury and immunohistochemical staining for caspase 3. RESULTS: When compared with median values, the control group, animals in the Hepat group had a lesser intestinal mucosal injury score (4.0 [range:2.0-5.0] vs 1.0 [range:1.0-2.0]; P < .01), decreased bacterial translocation in the portal and the systemic circulation at 24 hours of reperfusion (P < .05), and decreased portal and systemic endotoxin levels at 24 hours (P < .05). At 24 hours after reperfusion, mucosal protein carbonyls and malondialdehyde levels were decreased in Hepat animals (0.57 nmol/mg [range:0.32-0.70] vs 0.33 nmol/mg [range:0.03 0.53] and 3.85 nmol/mg [range:3.01-6.43] vs 3.27 nmol/mg [range:1.46-3.55], respectively; P < .05). There was no difference in tissue caspase staining. CONCLUSION: Bioartificial liver support seems to attenuate intestinal mucosal injury and gut barrier dysfunction after major hepatectomy. PMID- 26847804 TI - Recurrent cerebral ischaemic events in the setting of paroxysmal nocturnal haemoglobinuria. AB - The authors present a case of a 28-year-old man with a known history of paroxysmal nocturnal haemoglobinuria (PNH), under platelet antiaggregation, admitted following recurrent transitory arterial ischaemic attacks. Concomitant thrombosis of the superior mesenteric artery and bilateral renal infarction was found. Cardioembolism, namely patent foramen ovale, was excluded and anticoagulation added, with no further events on 10-month follow-up. PNH is a rare acquired disorder of haematopoietic stem cells, characterised by haemolytic anaemia, pancytopenia and thrombotic events classically involving the venous system. Reports of cerebral artery stroke and accompanying intra-abdominal arterial thrombosis are especially rare. Complementary investigation and treatment options in these patients are discussed. PMID- 26847803 TI - Long-term survival in patients with pancreatic ductal adenocarcinoma. AB - BACKGROUND: Long-term survival (LTS) is uncommon for patients with pancreatic ductal adenocarcinoma (PDAC). We sought to identify factors that predict 10-year, LTS after resection of PDAC. METHODS: We identified all patients with PDAC who underwent resection at UCLA after 1990 and included all patients eligible for observed LTS (1/1/1990-12/31/2004). An independent pathologist reconfirmed the diagnosis of PDAC in patients with LTS. Logistic regression was used to predict LTS on the basis of patient and tumor characteristics. RESULTS: Of 173 included patients, 53% were male, median age at diagnosis was 66 years, and median survival was 23 months. The rate of observed LTS was 12.1% (n = 21). Age, sex, number of lymph nodes evaluated, margin status, lymphovascular invasion, and adjuvant chemotherapy and radiation were not associated with LTS. The following were associated with LTS on bivariate analysis: low AJCC stage (Ia, Ib, IIa) (P = .034), negative lymph node status (P = .034), low grade (well-, moderately differentiated) (P = .001), and absence of perineural invasion (P = .019). Only low grade (odds ratio 7.17, P = .012) and absent perineural invasion (odds ratio 3.28, P = .036) were independently associated with increased odds of LTS. Our multivariate model demonstrated good discriminatory power for LTS, as indicated by a c-statistic of 0.7856. CONCLUSION: Absence of perineural invasion and low tumor grade were associated with greater likelihood of LTS. Understanding the tumor biology of LTS may provide critical insight into a disease that is typically marked by aggressive behavior and limited survival. PMID- 26847805 TI - Massive calcinosis cutis associated with primary Sjogren's syndrome. PMID- 26847806 TI - Tuberculous epididymo-orchitis masquerading as acute scrotum. AB - An 18-year-old boy, a refugee from Afghanistan, with no significant medical history, presented after 1 day of severe left testicular pain. History, clinical examination and scrotal ultrasound suggested the diagnosis of epididymo-orchitis. He was discharged on a 2-week course of amoxicillin/clavulanic acid. Six weeks later, he re-presented with a testicular abscess, continuous with the epididymal head. Incision and drainage led to laboratory confirmation of tuberculous infection. He was treated with isoniazid, rifampicin, ethambutol, pyrazinamide and vitamin B6 for 9 months, with good response. Despite meeting high-risk criteria for tuberculosis, our patient had a delayed diagnosis. We present the case and discuss the lessons learned. PMID- 26847808 TI - Toxic Effects of Sorafenib in Patients With Differentiated Thyroid Carcinoma Compared With Other Cancers. AB - IMPORTANCE: Sorafenib is approved by the US Food and Drug Administration for metastatic, radioactive iodine-refractory differentiated thyroid cancer. However, adverse effects common to the tyrosine kinase inhibitor class occur at a noticeably higher rate with sorafenib use in thyroid cancer patients. The mechanism for this increase in toxic effects is unknown. OBJECTIVE: To provide an overview of the adverse effect profile of sorafenib in differentiated thyroid cancer and summarizes the literature regarding the frequency and etiology of selected adverse effects, with particular emphasis on the hand-foot skin reaction. EVIDENCE REVIEW: A PubMed database search for relevant literature on this topic published within the last 15 years was conducted. Publications dealing with sorafenib and any of its common adverse effects were considered; this included randomized trials, observational studies, case reports or case series, and pertinent review articles. Given the lack of widespread literature on the topic, articles were generally not excluded from consideration unless there were serious flaws in study design. FINDINGS: The DECISION trial of sorafenib in patients with differentiated thyroid cancer demonstrated significantly higher rates of common adverse effects, most notably hand-foot skin reaction, diarrhea, and hypertension, compared with sorafenib experience in renal or hepatocellular cancer. Other phase 2 and 3 trials have also consistently shown these differences. This review details the putative mechanisms behind the increase in toxic effects, but further work is needed to fully explain the toxic effects differential seen when using the same drug in different cancers. CONCLUSIONS AND RELEVANCE: There is a distinct increase in the rate of occurrence of adverse effects of sorafenib when used in differentiated thyroid cancer compared with renal and hepatocellular cancer. While many theoretical explanations have been proposed, the exact mechanism for this differential in toxic effects remains unclear. PMID- 26847807 TI - Spontaneous rectus sheath haematoma in a deceased donor renal transplant recipient: a rare complication. AB - Rectus sheath haematoma (RSH) is rarely thought of as a cause of abdominal pain in renal transplant recipients. A 36-year-old woman, a post-deceased donor renal allograft transplant recipient for chronic interstitial nephritis, on triple drug immunosuppression (tacrolimus, mycophenolate mofetil and prednisolone) with basiliximab induction, developed acute vascular rejection and acute tubular injury with suspected antibody-mediated rejection. While on plasmapheresis and haemodialysis for delayed graft function, she developed acute left lower abdominal pain on the 16th postoperative day with tender swelling in the left paraumbilical region. CT of the abdomen showed a large haematoma in the left rectus sheath with no extension. The patient underwent haematoma evacuation through a left paramedian incision and had an uneventful recovery. Serum creatinine stabilised at 0.8 mg/dL and she is on regular follow-up with excellent graft function at 6 months. Diagnosis requires a high index of suspicion, and prompt treatment prevents morbidity and can expedite patient recovery. PMID- 26847809 TI - Capturing HBCy2: Using N,O-Chelated Complexes of Rhodium(I) and Iridium(I) for Chemoselective Hydroboration. AB - 1,3-N,O-chelated complexes of Rh(I) and Ir(I) cooperatively and reversibly stabilized the B-H bond of HBCy2 to afford six-membered metallaheterocycles (M=Rh (7) or Ir (8)) having a delta-[M]???H-B agostic interaction. Treatment of these Shimoi-type borane adducts 7 or 8 with both an aldehyde and an alkene resulted in chemoselective aldehyde hydroboration and reformation of the 1,3-N,O-chelated starting material. The observed chemoselectivity is inverted from that of free HBCy2 , which is selective for alkene hydroboration. PMID- 26847810 TI - Lysing bloom-causing alga Phaeocystis globosa with microbial algicide: An efficient process that decreases the toxicity of algal exudates. AB - Algicidal microbes could effectively remove the harmful algae from the waters. In this study, we were concerned with the ecological influence of an algicide extracted from Streptomyces alboflavus RPS, which could completely lyse the Phaeocystis globosa cells within two days. In microcosms, 4 MUg/mL of the microbial algicide could efficiently remove P. globosa cells without suppressing other aquatic organisms. Bioluminescent assays confirmed that the toxicity of microbial algicide at this concentration was negligible. Interestingly, the toxicity of P. globosa exudates was also significantly reduced after being treated with the algicide. Further experiments revealed that the microbial algicide could instantly increase the permeability of the plasma membrane and disturb the photosynthetic system, followed by the deformation of organelles, vacuolization and increasing oxidative stress. The pre-incubation of N-acetyl cysteine (NAC) verified that the rapid damages to the plasma membrane and photosynthetic system caused the algal death in the early phase, and the increasing oxidative stress killed the rest. The late accumulation and possible release of CAT also explained the decreasing toxicity of the algal culture. These results indicated that this microbial algicide has great potential in controlling the growth of P. globosa on site. PMID- 26847811 TI - Do All Women With Abnormal Sonographic Axillary Lymph Nodes Need a Biopsy? AB - PURPOSE: With the increased use of breast ultrasound for different indications, sonographically abnormal axillary lymph nodes are not a rare finding. We examined clinical and imaging characteristics in correlation with pathological reports of the sonographic guided biopsies to assess the yield of needle biopsy of these nodes. METHODS: Clinical, imaging and pathology data were collected for 171 consecutive patients who underwent sonographic guided needle biopsy of an abnormal lymph node between 2008 and 2013. Malignancy rates were examined for different clinical settings: palpable axillary mass, previous history of breast cancer, findings suggestive of a systemic disease, and those with a breast finding of low suspicion or an incidental abnormal axillary lymph node. Patients with newly diagnosed breast cancer were excluded. RESULTS: Twelve patients (7%) were found to have a malignancy on their axillary lymph node biopsy. Malignancy rates increased with age, and varied with clinical presentation: Axillary mass (8, 26%); history of breast cancer (2, 11%); systemic disease (0%) and breast finding of low suspicion or incidental abnormal lymph node on screening (1, 1%). Low rates of malignancy were found when the cortex was <6 mm (1, 0.8%). The most important imaging finding associated with malignancy was lack of a preserved hilum, in which case almost a third (10, 29%) of the biopsies were malignant. Only 1 of 89 women with a breast finding of low suspicion or an incidental abnormal axillary lymph node was found to have malignancy. In this case the lymph node had no hilum. CONCLUSIONS: In women without breast cancer, a highly suspicious breast mass or an axillary mass, more stringent criteria should be used when evaluating an abnormal axillary lymph node on sonography, as the malignancy rates are very low (1%). PMID- 26847812 TI - Factors Influencing Radiology Residents' Fellowship Training and Practice Preferences in Canada. AB - PURPOSE: The study aimed to examine the postresidency plans of Canadian radiology residents and factors influencing their fellowship choices and practice preferences, including interest in teaching and research. METHODS: Institutional ethics approval was obtained at McMaster University. Electronic surveys were sent to second to fifth-year residents at all 16 radiology residency programs across Canada. Each survey assessed factors influencing fellowship choices and practice preferences. RESULTS: A total of 103 (31%) Canadian radiology residents responded to the online survey. Over 89% from English-speaking programs intended to pursue fellowship training compared to 55% of residents from French-speaking programs. The most important factors influencing residents' decision to pursue fellowship training were enhanced employability (46%) and personal interest (47%). Top fellowship choices were musculoskeletal imaging (19%), body imaging (17%), vascular or interventional (14%), neuroradiology (8%), and women's imaging (7%). Respondents received the majority of their fellowship information from peers (68%), staff radiologists (61%), and university websites (58%). Approximately 59% planned on practicing at academic institutions and stated that lifestyle (43%), job prospects (29%), and teaching opportunities (27%) were the most important factors influencing their decisions. A total of 89% were interested in teaching but only 46% were interested in incorporating research into their future practice. CONCLUSIONS: The majority of radiology residents plan on pursuing fellowship training and often receive their fellowship information from informal sources such as peers and staff radiologists. Fellowship directors can incorporate recruitment strategies such as mentorship programs and improving program websites. There is a need to increase resident participation in research to advance the future of radiology. PMID- 26847814 TI - Printed thin film transistors and CMOS inverters based on semiconducting carbon nanotube ink purified by a nonlinear conjugated copolymer. AB - Two innovative research studies are reported in this paper. One is the sorting of semiconducting carbon nanotubes and ink formulation by a novel semiconductor copolymer and second is the development of CMOS inverters using not the p-type and n-type transistors but a printed p-type transistor and a printed ambipolar transistor. A new semiconducting copolymer (named P-DPPb5T) was designed and synthesized with a special nonlinear structure and more condensed conjugation surfaces, which can separate large diameter semiconducting single-walled carbon nanotubes (sc-SWCNTs) from arc discharge SWCNTs according to their chiralities with high selectivity. With the sorted sc-SWCNTs ink, thin film transistors (TFTs) have been fabricated by aerosol jet printing. The TFTs displayed good uniformity, low operating voltage (+/-2 V) and subthreshold swing (SS) (122-161 mV dec(-1)), high effective mobility (up to 17.6-37.7 cm(2) V(-1) s(-1)) and high on/off ratio (10(4)-10(7)). With the printed TFTs, a CMOS inverter was constructed, which is based on the p-type TFT and ambipolar TFT instead of the conventional p-type and n-type TFTs. Compared with other recently reported inverters fabricated by printing, the printed CMOS inverters demonstrated a better noise margin (74% 1/2 Vdd) and was hysteresis free. The inverter has a voltage gain of up to 16 at an applied voltage of only 1 V and low static power consumption. PMID- 26847813 TI - Bevacizumab and temozolomide versus temozolomide alone as neoadjuvant treatment in unresected glioblastoma: the GENOM 009 randomized phase II trial. AB - We sought to determine the impact of bevacizumab on reduction of tumor size prior to chemoradiotherapy in unresected glioblastoma patients. Patients were randomized 1:1 to receive temozolomide (TMZ arm) or temozolomide plus bevacizumab (TMZ + BEV arm). In both arms, neoadjuvant treatment was temozolomide (85 mg/m(2), days 1-21, two 28-day cycles), concurrent radiation plus temozolomide, and six cycles of adjuvant temozolomide. In the TMZ + BEV arm, bevacizumab (10 mg/kg) was added on days 1 and 15 of each neoadjuvant cycle and on days 1, 15 and 30 of concurrent treatment. The primary endpoint was investigator-assessed response to neoadjuvant treatment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the impact on outcome of MGMT methylation in tumor and serum. One hundred and two patients were included; 43 in the TMZ arm and 44 in the TMZ + BEV arm were evaluable for response. Results favored the TMZ + BEV arm in terms of objective response (3 [6.7 %] vs. 11 [22.9 %]; odds ratio 4.2; P = 0.04). PFS and OS were longer in the TMZ + BEV arm, though the difference did not reach statistical significance. MGMT methylation in tumor, but not in serum, was associated with outcome. More patients experienced toxicities in the TMZ + BEV than in the TMZ arm (P = 0.06). The combination of bevacizumab plus temozolomide is more active than temozolomide alone and may well confer benefit in terms of tumor shrinkage in unresected patients albeit at the expense of greater toxicity. PMID- 26847815 TI - Signaling pathways involving adenosine A2A and A2B receptors in wound healing and fibrosis. AB - Collagen and matrix deposition by fibroblasts is an essential part of wound healing but also contributes to pathologic remodeling of organs leading to substantial morbidity and mortality. Adenosine, a small molecule generated extracellularly from adenine nucleotides as a result of direct stimulation, hypoxia, or injury, acts via a family of classical seven-pass G protein-coupled protein receptors, A2A and A2B, leading to generation of cAMP and activation of downstream targets such as PKA and Epac. These effectors, in turn, lead to fibroblast activation and collagen synthesis. The regulatory actions of these receptors likely involve multiple interconnected pathways, and one of the more interesting aspects of this regulation is opposing effects at different levels of cAMP generated. Additionally, adenosine signaling contributes to fibrosis in organ-specific ways and may have opposite effects in different organs. The development of drugs that selectively target these receptors and their signaling pathways will disrupt the pathogenesis of fibrosis and slow or arrest the progression of the important diseases they underlie. PMID- 26847817 TI - Effect of dietary probiotic, prebiotic and synbiotic supplementation on performance, immune responses, intestinal morphology and bacterial populations in broilers. AB - This study was conducted to investigate the effects of probiotic (Primalac), prebiotic (TechnoMos) and synbiotic (Primalac + TechnoMos) supplementation on performance, immune responses, intestinal morphology and bacterial populations of ileum in broilers. A total of 240 one-day-old broiler chicks were randomly divided into four treatment groups which included 60 birds. Control group did not receive any treatment. The chicks in the second, third and fourth groups were fed probiotic (0.9 g/kg), prebiotic (0.9 g/kg) and probiotic (0.9 g/kg) plus probiotic (0.9 g/kg; synbiotic), respectively, at entire period. Daily feed intake, daily weight gain and feed conversion ratio were evaluated. The birds were immunized by sheep red blood cell (SRBC) on days 12 and 29 of age and serum antibody titres were measured on days 28, 35 and 42. Newcastle vaccines administered on days 9, 18 and 27 to chicks and blood samples were collected on day 42. Intestinal morphometric assessment and enumeration of intestinal bacterial populations were performed on day 42. The results indicated that consumption of probiotic, prebiotic and synbiotic had no significant effect on daily feed intake, daily body weight gain, feed conversion ratio, carcass traits, intestinal morphology and bacterial populations of ileum (p > 0.05). Consumption of prebiotic increased total and IgM anti-SRBC titres on days 28 and 42 and antibody titre against Newcastle virus disease on day 42 (p < 0.05). Synbiotic increased only total anti-SRBC on day 28 (p < 0.05). It is concluded that consumption of prebiotic increased humoral immunity in broilers. Therefore, supplementation of diet with prebiotic for improvement of humoral immune responses is superior to synbiotic supplementation. PMID- 26847816 TI - Multiple Myeloma in Pregnancy--A Review of the Literature and a Case Series. AB - Multiple myeloma (MM) typically affects older patients with a median age at diagnosis of 67 to 70 years and only 3% of cases are diagnosed before the age of 40. Moreover, MM is more common in men. Therefore, pregnancy rarely occurs in patients with MM and only 37 cases of MM in pregnancy have been reported in the literature. Herein we report an additional 5 cases. The diagnosis of MM might be problematic in this context because some of the symptoms and signs, such as back pain and anemia, can be attributed to pregnancy. Furthermore, if the patient wishes to continue her pregnancy, therapeutic options are currently limited. The list of agents that can be safely administered in pregnant women includes glucocorticoids. Moreover, any continuation of pregnancy has obvious long-term psychosocial repercussions for the patient and her family because of the currently incurable nature of MM. The reported cases of MM in pregnancy represent a spectrum of clinical manifestations. The selection of efficacious and safe treatments is challenging, especially if continuation of pregnancy is desired. Although some authors postulate that pregnancy might lead to progression of MM, data are limited and no consensus on this point has been reached. PMID- 26847818 TI - The MAPK pathway is involved in the regulation of rapid pacing-induced ionic channel remodeling in rat atrial myocytes. AB - Alterations to the expression L-type calcium channels (LTCCs) and Kv4.3 potassium channels form the possible basis of atrial electrical remodeling during rapid pacing. The mitogen-activated protein kinase (MAPK) pathway is affected by increases in cytoplasmic Ca2+, and therefore represents an attractive candidate for the regulation and mediation of Ca2+-induced ion channel remodeling. The present study aimed to investigate alterations to the ion channel-MAPK axis, and to determine its influence on ion channel remodeling during atrial fibrillation. Rat atrial myocytes were isolated, cultured, and in vitro rapid pacing was established. Intracellular Ca2+ signals were monitored using the Fluo-3/AM Ca2+ indicator. Verapamil, PD98058 and SB203580 were added to the culture medium of various groups at specific time-points. The mRNA expression levels of LTCC alpha1c and Kv4.3 potassium channels were detected by reverse transcription polymerase chain reaction. Western blotting was performed to determine the expression levels of channel and signaling proteins. The results demonstrated that fast pacing significantly increased the intracellular Ca2+ concentration in atrial myocytes, whereas treatment with verapamil markedly inhibited this increase. In addition, verapamil significantly antagonized the rapid pacing induced activation of extracellular signal-regulated kinase (ERK) and p38MAPK. These results indicated that the MAPK pathway may have an important role in the opening of LTCCs, and alterations to MAPK molecule expression could affect the expression and remodeling of ion channels. PMID- 26847819 TI - Metformin inhibits growth of human non-small cell lung cancer cells via liver kinase B-1-independent activation of adenosine monophosphate-activated protein kinase. AB - Metformin, the most widely administered oral anti-diabetic therapeutic agent, exerts its glucose-lowering effect predominantly via liver kinase B1 (LKB1) dependent activation of adenosine monophosphate-activated protein kinase (AMPK). Accumulating evidence has demonstrated that metformin possesses potential antitumor effects. However, whether the antitumor effect of metformin is via the LKB1/AMPK signaling pathway remains to be determined. In the current study, the effects of metformin on proliferation, cell cycle progression, and apoptosis of human non-small cell lung cancer (NSCLC) H460 (LKB1-null) and H1299 (LKB1 positive) cells were assessed, and the role of LKB1/AMPK signaling in the anti growth effects of metformin were investigated. Cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell cycle distribution and apoptosis were assessed by flow cytometry, and protein expression levels were measured by western blotting. Metformin inhibited proliferation, induced significant cell cycle arrest at the G0-G1 phase and increased apoptosis in NSCLC cells in a time- and concentration-dependent manner, regardless of the level of LKB1 protein expression. Furthermore, knockdown of LKB1 with short hairpin RNA (shRNA) did not affect the antiproliferative effect of metformin in the H1299 cells. Metformin stimulated AMPK phosphorylation and subsequently suppressed the phosphorylation of mammalian target of rapamycin and its downstream effector, 70-kDa ribosomal protein S6 kinase in the two cell lines. These effects were abrogated by silencing AMPK with small interfering RNA (siRNA). In addition, knockdown of AMPK with siRNA inhibited the effect of metformin on cell proliferation in the two cell lines. These results provide evidence that the growth inhibition of metformin in NSCLC cells is mediated by LKB1-independent activation of AMPK, indicating that metformin may be a potential therapeutic agent for the treatment of human NSCLC. PMID- 26847820 TI - Connective processing by bilingual children and monolinguals with specific language impairment: distinct profiles. AB - Production studies show that both Russian-speaking children with specific language impairment (SLI) and bilingual children for whom Russian is a non dominant language have difficulty distinguishing between the near-synonymous connectives i 'and' and a 'and/but'. I is a preferred connective when reference is maintained, whereas a is normally used for reference shift. We report an eye tracking experiment comparing connective processing by Russian-speaking monolinguals with typical language development (TLD) with that of Russian-Dutch bilinguals and Russian-speaking monolinguals with SLI (age 5-6). The results demonstrate that the processing profiles of monolinguals with TLD and bilinguals are similar: both groups use connective semantics immediately for predicting further discourse. In contrast, children with SLI do not show sensitivity to these semantic differences. Despite similar production profiles, bilinguals and monolinguals with SLI are clearly different in connective processing. We discuss the implications of these results for the possible causes of the errors in the two populations. PMID- 26847821 TI - Preliminary definitions of 'flare' in axial spondyloarthritis, based on pain, BASDAI and ASDAS-CRP: an ASAS initiative. AB - INTRODUCTION: Flares may be used as outcomes in axial spondyloarthritis (axSpA) trials or observational studies. The objective was to develop a definition for 'flare' (or worsening) in axSpA, based on validated composite indices, to be used in the context of clinical trial design. METHODS: (1) Systematic literature review of definitions of 'flare' in published randomised controlled trials in axSpA. (2) Vignette exercise: 140 scenarios were constructed for a typical patient with axSpA seen at two consecutive visits. Each scenario included a change in one of the following outcomes: pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BASDAI plus C-reactive protein (CRP) or Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP. Each Assessment of Spondyloarthritis (ASAS) expert determined if every scenario from a random sample of 46 scenarios was considered a flare (yes/no). Receiver-operating characteristic (ROC) analyses were applied to derive optimal cut-off values. (3) ASAS consensus was reached. RESULTS: (1) The literature review yielded 38 studies using some definition of 'flare', with 27 different definitions indicating important heterogeneity. The most frequent definitions were based on BASDAI changes or pain changes. (2) 121 ASAS experts completed 4999 flare assessments. The areas under the ROC curves were high (range: 0.88-0.89). Preliminary cut-offs for pain (N=3), BASDAI (N=5) and ASDAS-CRP (N=4) were chosen, with a range of sensitivity 0.60-0.99 and range of specificity 0.40-0.94 against the expert's opinions. CONCLUSIONS: This data-driven ASAS consensus process has led to 12 preliminary draft definitions of 'flare' in axSpA, based on widely used indices. These preliminary definitions will need validation in real patient data. PMID- 26847822 TI - Reporting of potential immunogenicity with biologic drugs: clarity and accuracy required. PMID- 26847823 TI - Efficient Terahertz detection in black-phosphorus nano-transistors with selective and controllable plasma-wave, bolometric and thermoelectric response. AB - The ability to convert light into an electrical signal with high efficiencies and controllable dynamics, is a major need in photonics and optoelectronics. In the Terahertz (THz) frequency range, with its exceptional application possibilities in high data rate wireless communications, security, night-vision, biomedical or video-imaging and gas sensing, detection technologies providing efficiency and sensitivity performances that can be "engineered" from scratch, remain elusive. Here, by exploiting the inherent electrical and thermal in-plane anisotropy of a flexible thin flake of black-phosphorus (BP), we devise plasma-wave, thermoelectric and bolometric nano-detectors with a selective, switchable and controllable operating mechanism. All devices operates at room-temperature and are integrated on-chip with planar nanoantennas, which provide remarkable efficiencies through light-harvesting in the strongly sub-wavelength device channel. The achieved selective detection (~5-8 V/W responsivity) and sensitivity performances (signal-to-noise ratio of 500), are here exploited to demonstrate the first concrete application of a phosphorus-based active THz device, for pharmaceutical and quality control imaging of macroscopic samples, in real-time and in a realistic setting. PMID- 26847824 TI - A pathogenic IFNalpha, BLyS and IL-17 axis in Systemic Lupus Erythematosus patients. AB - This study aims to analyze in depth the role of IFNalpha in the upregulation of BLyS in different leukocyte populations and the possible relationship of these molecules with IL-17 and other pathogenic cytokines in SLE. Thus, IFNAR1 and membrane BLyS (mBLyS) expression was upregulated on various blood cell types from patients and closely correlated in all individuals. Moreover, BLyS serum levels associated positively with IFNalpha and IL-17A amounts, as well as with mBLyS on B cells and neutrophils. Interestingly, mBLyS on neutrophils was also correlated with IL-17A levels. Additionally, intracellular IL-17A expression was increased in both CD4(+) lymphocytes and neutrophils from patients, and IL-17(+)CD4(+) T cell frequency was associated with serum IFNalpha and IFNRA1 expression on B cells. Finally, in vitro assays support an IFNalpha role in the activation of Th17 cells in SLE. In conclusion, these data suggest that IFNalpha, BLyS and IL 17 could form a pathological axis in SLE, involving T and B lymphocytes, monocytes, DCs and neutrophils, which act in a vicious circle that encourage the preexisting inflammation and propagate the disease process. PMID- 26847825 TI - Towards the Development of a Mobile Phonopneumogram: Automatic Breath-Phase Classification Using Smartphones. AB - Correct labeling of breath phases is useful in the automatic analysis of respiratory sounds, where airflow or volume signals are commonly used as temporal reference. However, such signals are not always available. The development of a smartphone-based respiratory sound analysis system has received increased attention. In this study, we propose an optical approach that takes advantage of a smartphone's camera and provides a chest movement signal useful for classification of the breath phases when simultaneously recording tracheal sounds. Spirometer and smartphone-based signals were acquired from N = 13 healthy volunteers breathing at different frequencies, airflow and volume levels. We found that the smartphone-acquired chest movement signal was highly correlated with reference volume (rho = 0.960 +/- 0.025, mean +/- SD). A simple linear regression on the chest signal was used to label the breath phases according to the slope between consecutive onsets. 100% accuracy was found for the classification of the analyzed breath phases. We found that the proposed classification scheme can be used to correctly classify breath phases in more challenging breathing patterns, such as those that include non-breath events like swallowing, talking, and coughing, and alternating or irregular breathing. These results show the feasibility of developing a portable and inexpensive phonopneumogram for the analysis of respiratory sounds based on smartphones. PMID- 26847826 TI - Electric stimulation of the ears ameliorated learning and memory impairment in rats with cerebral ischemia-reperfusion injury. AB - Ear acupuncture enhances the secretion of acetylcholine, which has anti inflammatory effects. Here we want to investigate the effect of electric stimulation (ES) of the ears on learning and memory impairment in rats with cerebral ischemia-reperfusion injury. At 24 h after reperfusion, 2-Hz ES was applied to the ears for 20 min/day (10 min for each ear) for 7 days continuously. The step-through time of the passive avoidance test was greater in the ES group than in the control group (300.0 +/- 0.0 s vs 45.0 +/- 26.7 s, p < 0.05). Our results showed that neither neurological deficit score nor motor functions were improved after 2-Hz ES (4.0 +/- 0 vs 4.5 +/- 0.8, p > 0.05). The numbers of nicotinic acetylcholine receptor alpha4 positively stained cells in the CA2 and dentate gyrus of the hippocampus were 19.0 +/- 11.5 and 269.2 +/- 79.3, respectively, in the ES group, which were greater than those in the control group (7.0 +/- 5.9 and 165.5 +/- 30.8, respectively) (both p < 0.05). These results suggested that 2-Hz ES of the ears ameliorated learning and memory impairment in rats with ischemia-reperfusion injury. ES of the ears has neuroprotective effects, which are related to acetylcholine release. PMID- 26847829 TI - MDR-TB, Isolation, and Anomie: Has Anyone Referred to Social Work? : Comment on "The Ethics of Isolation for Patients With Tuberculosis in Australia". AB - MDR-TB and admission to isolation can induce a situation in which individuals are normless, unable to achieve the social goals that they have learned to pursue. Described as anomie, this situation can induce deviant behaviour. Addressing the psychosocial ethics of MDR-TB and isolation, this paper responds to the call for consideration of resource allocation and liberty. PMID- 26847828 TI - The association between the ring finger protein 213 (RNF213) polymorphisms and moyamoya disease susceptibility: a meta-analysis based on case-control studies. AB - A number of studies assessed the association of ring finger protein 213 (RNF213) gene polymorphisms with moyamoya disease (MMD), but the results were not entirely consistent. This meta-analysis was performed to explore the relationship between RNF213 polymorphisms and moyamoya disease in Asian population. A systematic search from the PubMed, MEDLINE, EMBASE, ISI web of science, CNKI, China CBM and WANFANG DATA databases was conducted to retrieve published studies until March 2015. Statistical analyses were performed using the STATA12.0 software. Fixed or random effects model, subgroup analysis, sensitivity analysis, and publication bias were used to improve the comprehensive analysis. Eight papers including 904 MMD patients and 2258 controls were recruited in the meta-analysis. rs112735431 was closely associated with the risk of MMD among Asian population in all genetic models (dominant model: OR 103.39, 95 % CI 52.25-204.55, P = 1.69e-40; recessive model: OR 16.45, 95 % CI 6.00-45.10, P = 5.33e-08; additive model: OR 61.49, 95 % CI 22.07-171.33, P = 3.32e-15), especially in the Japanese population. Subgroup analysis revealed highly statistically significant higher risk in the patients with family histories. Although another polymorphism rs148731719 showed no significant association with the MMD, rs138130613 was found to be related to the higher risk in Chinese population (dominant model: OR 8.34, 95 % CI 1.72-40.47, P = 0.008). Our meta-analysis strengthens RNF213 rs112735431 is closely associated with the increased risk of MMD in Japanese, and the screening combined with rs112735431 and rs138130613may improve the detection rate for MMD in China. PMID- 26847830 TI - Non-Coding RNAs in Thyroid Cancer. AB - Non-coding (nc)RNAs are divided into small ncRNAs and long ncRNAs (lncRNAs). MicroRNAs (miRNAs) are small ncRNAS which are around 22 nucleotides in length that mediate post-transcriptional gene silencing. LncRNAs are greater than 200 bp in length. Each ncRNA can have multiple targets and can be regulated by multiple genetic factors. Because ncRNAs are not translated into proteins, they can only be detected at the nucleic acid level by in situ hybridization, by RT-PCR, or by sequencing which makes their detection more challenging in the routine pathology laboratory. A great deal of new information has accumulated about miRNAs in thyroid tissues during the past decade. Some of these studies have shown that deregulation of miRNAs may be useful in diagnostic pathology. Information about the role of lncRNA in the development of thyroid tumors is in the early stages of development, but new information is accumulating rapidly. In this review, we will discuss the recent progress in our understanding of the relationship between ncRNAs and the development of thyroid cancers and the potential uses of ncRNAs in the diagnosis and prognosis of thyroid tumors. PMID- 26847832 TI - Alleviating Effect of Active Hexose Correlated Compound (AHCC) on Chemotherapy Related Adverse Events in Patients with Unresectable Pancreatic Ductal Adenocarcinoma. AB - The present study was conducted to determine whether active hexose correlated compound (AHCC), a functional food extracted from cultured basidiomycetes, possesses the potential to attenuate adverse events in unresectable pancreas ductal adenocarcinoma (PDAC) patients receiving chemotherapy. Unresectable PDAC patients receiving gemcitabine treatment (GEM) as the first-line chemotherapy were prospectively divided into 2 groups according to AHCC intake (AHCC group, n = 35) or not (control group, n = 40). The patients in the AHCC group ingested 6.0 g of AHCC for 2 mo. Hematological and nonhematological toxicity was compared between the AHCC and control groups. The C-reactive protein (CRP) elevation and albumin decline of the AHCC group were significantly suppressed as compared to the control group during the GEM administration (P = 0.0012, P = 0.0007). Patients in the AHCC group had less frequency of taste disorder caused by GEM (17% vs. 56%, P = 0.0007). Frequency of grade 3 in the modified Glasgow Prognostic Score (mGPS) during chemotherapy was found significantly less in the AHCC group (14%) than the control group (53%, P = 0.0005). AHCC intake can be effective in reducing the adverse events associated with chemotherapy and may contribute to maintaining the QOL of patients with PDAC during GEM administration. PMID- 26847833 TI - Assessing the State of Contamination in a Historic Mining Town Using Sediment Chemistry. AB - The United States town of Aurora, Missouri, USA, stockpiled lead (Pb) and zinc (Zn) mining wastes from the early to mid-1900s in the form of chat piles. Clean up actions were undertaken at intervals in subsequent years including land leveling and removal of chat. This study assessed the current state of contamination by identifying areas where metals are present at toxic levels. For this purpose, stream sediment samples (N = 100) were collected over a 9 * 12 km area in and around Aurora. Their content of cadmium (Cd), Pb, and Zn were measured, and concentration maps were generated using ArcGIS to categorize affected areas. Metal concentrations varied over a wide range of values with the overall highest values observed in the north-northeast part of Aurora where abundant chat piles had been present. Comparison between observed concentrations and sediment-quality guidelines put the contaminated areas mentioned are above toxic levels for Cd, Pb and Zn. In contrast, levels in rural areas and the southern part of Aurora were at background levels, thus posing no threat to aquatic habitats. The fact that contamination is constrained to a relatively small area can be advantageously used to implement further remediation and, by doing so, to help protect the underlying karst aquifer. PMID- 26847831 TI - Cullin-5, a ubiquitin ligase scaffold protein, is significantly underexpressed in endometrial adenocarcinomas and is a target of miR-182. AB - Altered expression of cullin-5 (CUL5), a member of the cullin-RING E3 ubiquitin ligase family, has been implicated in a number of types of cancers including breast, cervical and hepatocellular cancers. In the present study, we found that CUL5 expression was significantly decreased in both endometrioid and serous endometrial adenocarcinomas with the more aggressive serous type displaying a higher reduction (-4.3-fold) than the less aggressive endometrioid type (-2.9 fold). Overexpression of CUL5 mRNA and protein in Ishikawa H endometrial cancer cells resulted in decreased cell proliferation and in a reduction in CUL5-RING E3 ligase downstream clients JAK2 and FAS-L. Finally, we demonstrated for the first time that CUL5 is a direct target of miR-182 that we previously showed to be significantly overexpressed in endometrial adenocarcinomas and we provided evidence that increased miR-182 expression is, at least in part, a result of demethylation of its upstream promoter. These data suggest a cascade in which miR 182 expression is epigenetically increased leading to decreased CUL5 expression and increased cellular proliferation. The final step in the cascade may be operating through a decrease in ubiquitination of pro-growth CUL5 ubiquitin ligase clients. This cascade offers a series of potential interventional steps involving epigenetic modification, miRNA and/or gene targeting and ubiquitination. PMID- 26847834 TI - How does the foraging behavior of large herbivores cause different associational plant defenses? AB - The attractant-decoy hypothesis predicts that focal plants can defend against herbivory by neighboring with preferred plant species when herbivores make decisions at the plant species scale. The repellent-plant hypothesis assumes that focal plants will gain protection by associating with nonpreferred neighbors when herbivores are selective at the patch scale. However, herbivores usually make foraging decisions at these scales simultaneously. The net outcomes of the focal plant vulnerability could depend on the spatial scale at which the magnitude of selectivity by the herbivores is stronger. We quantified and compared the within- and between-patch overall selectivity index (OSI) of sheep to examine the relationships between associational plant effects and herbivore foraging selectivity. We found that the sheep OSI was stronger at the within- than the between-patch scale, but focal plant vulnerability followed both hypotheses. Focal plants defended herbivory with preferred neighbors when the OSI difference between the two scales was large. Focal plants gained protection with nonpreferred neighbors when the OSI difference was narrowed. Therefore, the difference in selectivity by the herbivores between the relevant scales results in different associational plant defenses. Our study suggests important implications for understanding plant-herbivore interactions and grassland management. PMID- 26847835 TI - Design, Implementation and Results of a Mobile Clinic based Diabetes Screening Program from India. PMID- 26847836 TI - Reconceptualizing Autonomy: A Relational Turn in Bioethics. AB - History's judgment on the success of bioethics will not depend solely on the conceptual creativity and innovation in the field at the level of ethical and political theory, but this intellectual work is not insignificant. One important new development is what I shall refer to as the relational turn in bioethics. This development represents a renewed emphasis on the ideographic approach, which interprets the meaning of right and wrong in human actions as they are inscribed in social and cultural practices and in structures of lived meaning and interdependence; in an ideographic approach, the task of bioethics is to bring practice into theory, not the other way around. The relational turn in bioethics may profoundly affect the critical questions that the field asks and the ethical guidance it offers society, politics, and policy. The relational turn provides a way of correcting the excessive atomism of many individualistic perspectives that have been, and continue to be, influential in bioethics. Nonetheless, I would argue that most of the work reflecting the relational turn remains distinctively liberal in its respect for the ethical significance of the human individual. It moves away from individualism, but not from the value of individuality.In this review essay, I shall focus on how the relational turn has manifested itself in work on core concepts in bioethics, especially liberty and autonomy. Following a general review, I conclude with a brief consideration of two important recent books in this area: Jennifer Nedelsky's Law's Relations and Rachel Haliburton's Autonomy and the Situated Self. PMID- 26847838 TI - Theoretical estimation of kinetic parameters for nucleophilic substitution reactions in solution: an application of a solution translational entropy model. AB - The kinetic parameters, such as activation entropy, activation enthalpy, activation free-energy, and reaction rate constant, for a series of nucleophilic substitution (SN) reactions in solution, are investigated using both a solution phase translational entropy model and an ideal gas-phase translational entropy model. The results obtained from the solution translational entropy model are in excellent agreement with the experimental values, while the overestimation of activation free-energy from the ideal gas-phase translational entropy model is as large as 6.9 kcal mol(-1). For some of the reactions studied, such as and in methanol, and and in aqueous solution, the explicit + implicit model, namely, a cluster-continuum type model, should be employed to account for the strong solvent-solute interactions. In addition, the explicit + implicit models have also been applied to the DMSO-H2O mixtures, which would open up a door to investigate the reactions in a mixed solvent using density functional theory (DFT) methods. PMID- 26847837 TI - Evaluation of Health Disparity in Bacterial Vaginosis and the Implications for HIV-1 Acquisition in African American Women. AB - There is a health disparity for both bacterial vaginosis (BV) and human immunodeficiency virus type 1 (HIV-1) infection in African American women that may be linked. The evidence that BV predisposes women to higher risk for HIV infection is well documented. The underlying mechanisms to support the epidemiological connections will require further investigations. This review explores the risk factors for BV disease with implications for HIV-1 acquisition in the context of race as a potential driver of the 20-fold increase in HIV-1 acquisition for African American women compared to white women. Specifically, it explores (i) disparities for BV in African American women, (ii) racial disparity for HIV-1 acquisition in African American women, (iii) common factors associated with BV and HIV acquisition in African American women, and (iv) potential mechanisms of the enhancement of HIV-1 transmission by BV. PMID- 26847840 TI - Defending a new hypothesis of how bariatric surgery works. PMID- 26847839 TI - HMGB1 induces apoptosis and EMT in association with increased autophagy following H/R injury in cardiomyocytes. AB - Hypoxia/reoxygenation (H/R) is a critical factor in the pathogenesis of tissue injury following myocardial infarction (MI) which can lead to tissue damage and pathological remodeling. Therefore, it is necessary to try and prevent myocardial H/R injury in order to optimize the treatment of MI. This study aimed to explore the functions and molecular mechanisms of action of high mobility group box 1 (HMGB1) and its role in H/R injury to H9c2 cells. The mRNA expression of levels genes were detected by RT-qPCR. The protein levels were examined by western blot analysis. The Beclin 1 expression level was further determined by immunocytochemistry (ICC). In addition, an HMGB1 overexpression vector and a shRNA lentiviral vector were constructed in order to induce the overexpression and silencing of HMGB1, respectively. The apoptotic rate of the H9c2 cells was determined by flow cytometry. The expression of miR-210 was markedly increased following the exposure of the cells to H/R, thus indicating that the cell model of H/R injury was successfully established. In addition, an in vivo model of MI was also created using rats. The mRNA and protein level of HMGB1 was found to be upregulated in the myocardial tissue of the rats with MI and in the H9c2 cells subjected to H/R injury. HMGB1 promoted apoptosis by increasing the expression of cleaved caspase-3 and the apoptotic rate of the cells, while decreasing the expression of Bcl-2 during H/R in the H9c2 cells. HMGB1 promoted epithelial-to mesenchymal transition (EMT) by reducing the protein level of the epithelial marker, E-cadherin, while increasing the expression of the mesenchymal markers, vimentin and fibroblast-specific protein (FSP), during H/R in the H9c2 cells. HMGB1 induced the apoptosis of the H9c2 cells and EMT following H/R in association with the induction of autophagy. HMGB1 induced autophagy by upregulating the expression of discoidin domain receptor 1 (DDR1) and downregulating the phosphorylation levels of mammalian target of rapamycin (mTOR). In conclusion, the findings of our study suggest that HMGB1 promotes apoptosis and EMT in association with the induction of autophagy through the upregulation of the expression of DDR1 and the downregulation of the phosphorylation of mTOR following H/R injury in H9c2 cells. PMID- 26847841 TI - MicroRNA expression pattern in pre-eclampsia (Review). AB - Pre-eclampsia (PE), a pregnancy complication, is a leading cause of maternal and fetal morbidity and mortality. Although its exact etiology and pathogenesis remain elusive, PE results from an interaction of inherited and non-inherited factors. The clinical symptoms of PE appear post-mid-stage of gestation and, at present, there are no early signs/markers for its onset and progression. MicroRNAs function as gene regulators, and are involved in development and pathology. A burgeoning number of studies have highlighted microRNAs as potential biomarkers for minimal invasive assessment. However, it remains a matter of debate as to which microRNA type is involved in PE onset and progression, as well as the clinical utility of testing for these species. In the present review, we have summarized the latest findings on the association of PE with the aberrant expression of placental microRNAs; in particular, those that are detectable in the blood. The current understanding of the mechanisms of microRNA-target gene interactions that underpin the involvement of microRNAs in the pathogenesis of PE is also discussed. PMID- 26847842 TI - Kinetically-controlled synthesis of ultra-small silica nanoparticles and ultra thin coatings. AB - The understanding of silica as a polymer-like globule allows us to synthesize ultra-small silica nanoparticles (NPs) via a kinetic controlled process. The synthetic system is quite simple with Tetraethyl orthosilicate (TESO) as the precursor and H2O as the solvent and reactant. The reaction conditions are gentle with a temperature of around 35 to 60 degrees C with an incubation time of 7-12 hours. The final product of the silica NPs is very uniform and could be as small as 10 nm. The silica NPs can further grow up to 18 nm under the controlled addition of the precursors. Also, these silica NPs can be used as seeds to generate larger silica NPs with sizes ranging from 20 to 100 nm, which can be a useful supplement to the size range made by the traditional Stober method. Moreover, these ultra-small Au NPs can be used as a depletion reagent or as building blocks for an ultrathin silica coating, which has significant applications in fine-tuning the plasmons of AuNPs and thin spacers for surface enhanced spectroscopies. PMID- 26847843 TI - Hybrid 2D-nanomaterials-based electrochemical immunosensing strategies for clinical biomarkers determination. AB - Owing to the outstanding conductivity and biocompatibility as well as numerous other fascinating properties of two-dimensional (2D)-nanomaterials, 2D-based nanohybrids have shown unparalleled superiorities in the field of electrochemical biosensors. This review highlights latest advances in electrochemical immunosensors for clinical biomarkers based on different hybrid 2D-nanomaterials. Particular attention will be given to hybrid nanostructures involving graphene and other graphene-like 2D-layered nanomaterials (GLNs). Several recent strategies for using such 2D-nanomaterial heterostructures in the development of modern immunosensors, both for tagging or modifying electrode transducers, are summarized and discussed. These hybrid nanocomposites, quite superior than their rival materials, will undoubtedly have an important impact within the near future and not only in clinical areas. Current challenges and future perspectives in this rapidly growing field are also outlined. PMID- 26847844 TI - Country roads, take me home... to my friends: How intelligence, population density, and friendship affect modern happiness. AB - We propose the savanna theory of happiness, which suggests that it is not only the current consequences of a given situation but also its ancestral consequences that affect individuals' life satisfaction and explains why such influences of ancestral consequences might interact with intelligence. We choose two varied factors that characterize basic differences between ancestral and modern life - population density and frequency of socialization with friends - as empirical test cases. As predicted by the theory, population density is negatively, and frequency of socialization with friends is positively, associated with life satisfaction. More importantly, the main associations of life satisfaction with population density and socialization with friends significantly interact with intelligence, and, in the latter case, the main association is reversed among the extremely intelligent. More intelligent individuals experience lower life satisfaction with more frequent socialization with friends. This study highlights the utility of incorporating evolutionary perspectives in the study of subjective well-being. PMID- 26847845 TI - Surgical removal of third molars and periodontal tissues of adjacent second molars. AB - OBJECTIVES: The aim of this study was to investigate the effect of mandibular third-molar (M3) removal on periodontal health of adjacent second molars (M2). Probing pocket depths (PPD) and probing attachment levels (PAL) have been described for primary outcome. As cofactors involved, gender, complications, two suture materials and two types of impaction were chosen as secondary outcomes. MATERIALS AND METHODS: Seventy-eight patients (49 female; mean age: 16.0 +/- 2.0 years) with 78 asymptomatic impacted mandibular M3 were included in this study. Plaque and gingival indices, PPD and PAL were recorded prior and 6 months after surgery. Impacted teeth were classified as either fully impacted (completely within in the bone) or submucosal (fully covered by oral mucosa). RESULTS: Average baseline PPD was reduced from 3.3 mm to 2.6 mm after 6 months (p < 0.05). Average PAL was reduced from 3.0 to 2.5 mm (p < 0.05). Preoperative PPD >= 4 mm at the distolingual and distobuccal sites was positively correlated with clinical improvement (PPD: p < 0.05; PAL: p < 0.05). The impaction class was also identified as positive cofactor for PPD (p = 0.039), but not for PAL. CONCLUSIONS: Young patients may benefit from an early removal of mandibular M3, especially in the presence of certain cofactors. PMID- 26847846 TI - Female fertility preservation: a clinical perspective. AB - For patients with cancer, preserving the ability to start a family at a time of their choosing is especially important and may influence decisions pertaining to cancer treatment. For other women who have delayed childbearing for personal or professional reasons, fertility preservation offers the possibility of having a biological child regardless of age. Though these women may be interested in or benefit from fertility preservation, fertility preservation services remain underutilized. While embryo and oocyte cryopreservation remain the standard strategies for female fertility preservation recommended by the American Society of Reproductive Medicine, the American Society of Clinical Oncology and the European Society of Medical Oncology, other strategies (e.g. pharmacological protection of the ovaries and ovarian tissue cryopreservation) are the subject of increasing research. This review will present new data that have become available over the past few years pertaining to all available methods of fertility preservation. PMID- 26847847 TI - A Prospective Study of Proton Beam Reirradiation for Esophageal Cancer. AB - PURPOSE: Reirradiation to the esophagus carries a significant risk of complications. Proton therapy may offer an advantage in the reirradiation setting due to the lack of exit dose and potential sparing of previously radiated normal tissues. METHODS AND MATERIALS: Between June 2010 and February 2014, 14 patients with a history of thoracic radiation and newly diagnosed or locally recurrent esophageal cancer began proton beam reirradiation on a prospective trial. Primary endpoints were feasibility and acute toxicity. Toxicity was graded according Common Toxicity Criteria version 4.0. RESULTS: The median follow-up was 10 months (2-25 months) from the start of reirradiation. Eleven patients received concurrent chemotherapy. The median interval between radiation courses was 32 months (10-307 months). The median reirradiation prescription dose was 54.0 Gy (relative biological effectiveness [RBE]) (50.4-61.2 Gy[RBE]), and the median cumulative prescription dose was 109.8 Gy (76-129.4 Gy). Of the 10 patients who presented with symptomatic disease, 4 patients had complete resolution of symptoms, and 4 had diminished or stable symptoms. Two patients had progressive symptoms. The median time to symptom recurrence was 10 months. Maximum acute nonhematologic toxicity attributable to radiation was grade 2 (64%, N=9), 3 (29%, N=4), 4 (0%), and 5 (7%, N=1). The acute grade 5 toxicity was an esophagopleural fistula more likely related to tumor progression than radiation. Grade 3 nonhematologic acute toxicities included dysphagia, dehydration, and pneumonia. There was 1 late grade 5 esophageal ulcer more likely related to tumor progression than radiation. There were 4 late grade 3 toxicities: heart failure, esophageal stenosis requiring dilation, esophageal ulceration from tumor, and percutaneous endoscopic gastrostomy tube dependence. The median time to local failure was 10 months, and the median overall survival was 14 months. CONCLUSIONS: Our data demonstrate that proton reirradiation is feasible, with an encouraging symptom control rate, modest radiation-related toxicity, and favorable survival in this high-risk population. PMID- 26847848 TI - Suppressing kidney angiotensinogen in blood pressure regulation. PMID- 26847849 TI - Expression profile of hydrogen sulfide and its synthases correlates with tumor stage and grade in urothelial cell carcinoma of bladder. AB - BACKGROUND: Hydrogen sulfide (H2S) is a newly discovered gas transmitter. It is synthesized by cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MPST). Endogenous hydrogen sulfide has never been studied in bladder cancer. PURPOSE: We evaluated H2S production and its synthases expression levels in transitional cell carcinoma (urothelial cell carcinoma of bladder [UCB]) of human bladder tissue and cell lines. MATERIALS AND METHODS: Immunostaining was performed in urothelial cell lines and bladder specimens from 94 patients with UCB of different stages/grades. The expression levels/activities of CBS, CSE, and MPST of specimens and cell lines were analyzed by image semiquantity assay, western blot, and a sulfur sensitive electrode. We tried to find the correlation between hydrogen sulfide and its synthases with tumor stage in UCB. All experiments were repeated at least 3 times. RESULTS: Immunoreactivity for CBS, CSE, and MPST was detected in malignant uroepithelium and muscular layer of all tissues examined and cultured cells. The expression levels of CBS, CSE, and MPST were associated with UCB stage/grade. Muscle-invasive bladder cancer samples showed the highest production of H2S (52.6+/-2.91 nmol/[mg.min]) among all tested samples and EJ cells (transitional cell carcinoma, grade IIIshowed the highest production of H2S among all tested cell lines (53.3+/-7.02nmol/[mg.min]). CONCLUSIONS: Protein levels and catalytic activities of CBS, CSE, and MPST increased with the increase of malignant degrees in human bladder tissues and human UCB cell lines. Our findings may promote the application of these novel enzymes to UCB diagnosis or treatment. PMID- 26847850 TI - Physiological signalling to myosin phosphatase targeting subunit-1 phosphorylation in ileal smooth muscle. AB - KEY POINTS: The extent of myosin regulatory light chain phosphorylation (RLC) necessary for smooth muscle contraction depends on the respective activities of Ca(2+) /calmodulin-dependent myosin light chain kinase and myosin light chain phosphatase (MLCP), which contains a regulatory subunit MYPT1 bound to the phosphatase catalytic subunit and myosin. MYPT1 showed significant constitutive T696 and T853 phosphorylation, which is predicted to inhibit MLCP activity in isolated ileal smooth muscle tissues, with additional phosphorylation upon pharmacological treatment with the muscarinic agonist carbachol. Electrical field stimulation (EFS), which releases ACh from nerves, increased force and RLC phosphorylation but not MYPT1 T696 or T853 phosphorylation. The conditional knockout of MYPT1 or the knockin mutation T853A in mice had no effect on the frequency-maximal force responses to EFS in isolated ileal tissues. Physiological RLC phosphorylation and force development in ileal smooth muscle depend on myosin light chain kinase and MLCP activities without changes in constitutive MYPT1 phosphorylation. ABSTRACT: Smooth muscle contraction initiated by myosin regulatory light chain (RLC) phosphorylation is dependent on the relative activities of Ca(2+) /calmodulin-dependent myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP). We have investigated the physiological role of the MLCP regulatory subunit MYPT1 in ileal smooth muscle in adult mice with (1) smooth muscle-specific deletion of MYPT1; (2) non-phosphorylatable MYPT1 containing a T853A knockin mutation; and (3) measurements of force and protein phosphorylation responses to cholinergic neurostimulation initiated by electric field stimulation. Isolated MYPT1-deficient tissues from MYPT1(SM-/-) mice contracted and relaxed rapidly with moderate differences in sustained responses to KCl and carbachol treatments and washouts, respectively. Similarly, measurements of regulatory proteins responsible for RLC phosphorylation during contractions also revealed moderate changes. There were no differences in contractile or RLC phosphorylation responses to carbachol between tissues from normal mice vs. MYPT1 T853A knockin mice. Quantitatively, there was substantial MYPT1 T696 and T853 phosphorylation in wild-type tissues under resting conditions, predicting a high extent of MLCP phosphatase inhibition. Reduced PP1cdelta activity in MYPT1-deficient tissues may be similar to attenuated MLCP activity in wild-type tissues resulting from constitutively phosphorylated MYPT1. Electric field stimulation increased RLC phosphorylation and force development in tissues from wild-type mice without an increase in MYPT1 phosphorylation. Thus, physiological RLC phosphorylation and force development in ileal smooth muscle appear to be dependent on MLCK and MLCP activities without changes in constitutive MYPT1 phosphorylation. PMID- 26847851 TI - Functional studies on circulating and disseminated tumor cells in carcinoma patients. AB - Despite numerous clinical studies indicating the clinical relevance of circulating tumor cells (CTCs) in blood and disseminated tumor cells (DTCs) in the bone marrow of cancer patients, the functional properties of these cells are largely unknown. The focus of this review is to emphasize how functional studies on viable CTCs and DTCs can enlarge the spectrum of applications of "liquid biopsies". The low number of CTCs in the peripheral blood and DTCs in the bone marrow and the fact that carcinoma cells are difficult to culture are major challenges. Significant advances in the in vitro and in vivo expansion of CTCs and DTCs from cancer patients have been achieved, which enable us now to study the functional properties of these cells. Here, we discuss published data about functional studies on CTCs and DTCs using in vitro cultivation and in vivo xenograft models. Functional analyses on CTCs and DTCs offer the possibility to identify the metastasis-initiating cells. Moreover, CTC-derived cell lines and xenografts might point to new therapeutic targets and can be used for drug development. PMID- 26847852 TI - Implementing competency based admissions at the Albert Einstein College of Medicine. AB - The Albert Einstein College of Medicine (Einstein) was founded in 1955 during an era of limited access to medical school for women, racial minorities, and many religious and ethnic groups. Located in the Bronx, NY, Einstein seeks to educate physicians in an environment of state-of-the-art scientific inquiry while simultaneously fulfilling a deep commitment to serve its community by providing the highest quality clinical care. A founding principle of Einstein, the basis upon which Professor Einstein agreed to allow the use of his name, was that admission to the student body would be based entirely on merit. To accomplish this, Einstein has long used a 'holistic' approach to the evaluation of its applicants, actively seeking a diverse student body. More recently, in order to improve its ability to identify students with the potential to be outstanding physicians, who will both advance medical knowledge and serve the pressing health needs of a diverse community, the Committee on Admissions reexamined and restructured the requirements for admission. These have now been categorized as four 'Admissions Competencies' that an applicant must demonstrate. They include: 1) cocurricular activities and relevant experiences; 2) communication skills; 3) personal and professional development; and 4) knowledge. The purpose of this article is to describe the process that resulted in the introduction and implementation of this competency based approach to the admission process. PMID- 26847853 TI - Cultural humility: treating the patient, not the illness. PMID- 26847854 TI - Ultraviolet Laser-induced ignition of RDX single crystal. AB - The RDX single crystals are ignited by ultraviolet laser (355 nm, 6.4 ns) pulses. The laser-induced damage morphology consisted of two distinct regions: a core region of layered fracture and a peripheral region of stripped material surrounding the core. As laser fluence increases, the area of the whole crack region increases all the way, while both the area and depth of the core region increase firstly, and then stay stable over the laser fluence of 12 J/cm(2). The experimental details indicate the dynamics during laser ignition process. Plasma fireball of high temperature and pressure occurs firstly, followed by the micro explosions on the (210) surface, and finally shock waves propagate through the materials to further strip materials outside and yield in-depth cracks in larger surrounding region. The plasma fireball evolves from isotropic to anisotropic under higher laser fluence resulting in the damage expansion only in lateral direction while maintaining the fixed depth. The primary insights into the interaction dynamics between laser and energetic materials can help developing the superior laser ignition technique. PMID- 26847855 TI - Acute sacroiliitis. AB - The purpose of this study was to review the data on the etiology, risk factors, clinical presentations, and diagnosis of acute sacroiliitis. A Pubmed search utilizing the indexing term "acute sacroiliitis" was conducted and the data pertinent to the aim of the review was extracted and organized in accordance with the preplanned structure of the manuscript. The diagnosis of acute sacroiliitis is often challenging because of both the relative rarity of this presentation and diverse character of acute sacroiliac pain, frequently mimicking other, more prevalent disorders. Technetium bone scintigraphy can localize the disease process to the sacroiliac joint, while computed tomography or magnetic resonance imaging can be used for the detailed characterization and the extent of the disease as well as the diagnosis of complications. Pyogenic sacroiliitis is by far the most common cause of acute sacroiliitis. Brucellosis, acute sacroiliitis in the course of reactive arthritis, and crystalline-induced sacroiliitis frequently imitate pyogenic sacroiliitis. Acute sacroiliitis can rarely be also related to hematological malignancies or treatment with isotretinoin. Awareness to the possibility of acute sacroiliitis and a thorough physical examination are the necessary prerequisites to its timely diagnosis, while the appropriate laboratory and imaging studies should confirm the precise diagnosis and direct the appropriate treatment strategy. PMID- 26847857 TI - [Influence of sample conservation on quantification of Hepatitis C Virus RNA]. PMID- 26847856 TI - Relationship of serum osteoprotegerin with arterial stiffness, preclinical atherosclerosis, and disease activity in patients with ankylosing spondylitis. AB - Patients with ankylosing spondylitis (AS) reportedly have a higher mortality and morbidity risk. Osteoprotegerin (OPG) was recently defined as an important cardiovascular (CV) marker in the general population. We aimed to assess the relationship of serum OPG levels with arterial stiffness, carotid intima media thickness (CIMT), and clinical and laboratory data in AS patients. We examined 60 AS patients without CV disease or risk factors and 50 healthy controls. Disease activity was evaluated using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS), whereas functional capacity was evaluated using the Bath Ankylosing Spondylitis Functional Index (BASFI). Serum OPG levels were measured with the enzyme-linked immunosorbent assay. Carotid-femoral pulse wave velocity (PWV) was used as an indicator of arterial stiffness, whereas CIMT (examined via carotid ultrasonography) was used to evaluate preclinical atherosclerosis. The mean serum OPG level, PWV, and CIMT were significantly higher in AS patients than in controls (106.7 +/- 50.9 vs. 58.1 +/- 12.7 pg/mL; 7.4 +/- 1.8 vs. 6.2 +/- 1.2 m/s; 0.72 +/- 0.13 vs. 0.57 +/- 0.07 mm, respectively; P < 0.001 for all). In AS patients, the serum OPG levels were not significantly correlated with PWV and CIMT but were significantly correlated with erthrocyte sedimentation rate, BASFI, and ASDAS. AS patients without CV disease or risk exhibited high OPG levels and increased PWV and CIMT values. Although OPG levels were not significantly correlated with PWV or CIMT, future long-term follow-up studies will help define the predictive value of OPG in these patients. PMID- 26847858 TI - Monolayer-to-bilayer transformation of silicenes and their structural analysis. AB - Silicene, a two-dimensional honeycomb network of silicon atoms like graphene, holds great potential as a key material in the next generation of electronics; however, its use in more demanding applications is prevented because of its instability under ambient conditions. Here we report three types of bilayer silicenes that form after treating calcium-intercalated monolayer silicene (CaSi2) with a BF4(-) -based ionic liquid. The bilayer silicenes that are obtained are sandwiched between planar crystals of CaF2 and/or CaSi2, with one of the bilayer silicenes being a new allotrope of silicon, containing four-, five- and six-membered sp(3) silicon rings. The number of unsaturated silicon bonds in the structure is reduced compared with monolayer silicene. Additionally, the bandgap opens to 1.08 eV and is indirect; this is in contrast to monolayer silicene which is a zero-gap semiconductor. PMID- 26847859 TI - mTOR treatment in lymphangioleiomyomatosis: the role of everolimus. AB - The orphan lung disease lymphangioleiomyomatosis (LAM) has until recently been untreatable other than by lung transplantation. However, improved understanding of underlying disease mechanisms has revealed the central role of constitutive up regulation of the mammalian target of rapamycin (mTOR) pathway in this disease. Although other pathways exist and are under investigation for treatment, several mTOR inhibitors are currently available and emerging information suggests that these may have some efficacy in preventing loss of lung function in LAM. This paper summarizes current understanding of treatment with mTOR inhibitors in LAM, and everolimus in particular. It outlines pharmacokinetics and pharmacodynamics relevant to the clinician, recent clinical studies, and issues with potential side effects. mTOR treatment is not yet available in most countries for LAM, but current data for treatment efficacy are impressive, and it is hoped that mTOR inhibition will soon be recognised as an important treatment of this disease. PMID- 26847860 TI - Evaluation of Posttransplantation Diabetes Mellitus After Liver Transplantation: Assessment of Insulin Administration as a Risk Factor. AB - BACKGROUND: Impaired glucose regulation posttransplantation can affect allograft survival and may lead to the development of posttransplant diabetes mellitus (PTDM). OBJECTIVES: The primary purpose of this study is to assess the difference in insulin burden between liver transplant patients who develop PTDM and patients who do not. METHODS: This was a single-center, retrospective study. Adult liver transplant recipients transplanted between January 1, 2005, and August 1, 2013, were included. PTDM was defined as: (1) use of an oral antihyperglycemic agent for >=30 consecutive days after transplant, (2) use of insulin >=30 consecutive days after transplant, or (3) hemoglobin A1C>=6.5 any time after transplant. RESULTS: Of the 114 patients included, 48 (42%) developed PTDM. The average 24 hour insulin requirement on the medical floors was 17.2 +/- 14.5 units in the PTDM group and 11.3 +/- 12.2 units in the PTDM-free group;P= 0.02. The average blood glucose level on the medical floor was 184.7 +/- 31.5 mg/dL in the PTDM group and 169.3 +/- 31.4 mg/dL in the PTDM-free group;P= 0.013. Multivariate analysis revealed that experiencing rejection was positively associated with the development of PTDM: adjusted odds ratio (AOR) = 3.237; 95% CI = 1.214-8.633. Basiliximab was negatively associated with the development of PTDM: AOR = 0.182; 95% CI = 0.040-0.836. CONCLUSION: Univariate analyses suggest that insulin burden is a positive risk factor for the development of PTDM; this association is lost in multivariate analyses. Rejection was a positive predictor, and use of basiliximab was a negative predictor for the development of PTDM. PMID- 26847861 TI - Comment: Association Between Topiramate Use and Serum Bicarbonate Levels in a Veteran Population. PMID- 26847862 TI - Recently Retracted Clinical Trial Serves as an Important Reminder. PMID- 26847863 TI - Paracorporeal lung assist device in infants and toddlers: Coming of age? PMID- 26847864 TI - Ophthalmologist who filed 99 claims against NHS trusts acted vexatiously and wasted resources, GMC says. PMID- 26847865 TI - Evaluation of in vitro storage characteristics of cold stored platelet concentrates with N acetylcysteine (NAC). AB - Platelets play a vital role in hemostasis and thrombosis, and their demand and usage has multiplied many folds over the years. However, due to the short life span and storage constraints on platelets, it is allowed to store them for up to 7 days at room temperature (RT); thus, there is a need for an alternative storage strategy for extension of shelf life. Current investigation involves the addition of 50 mM N acetylcysteine (NAC) in refrigerated concentrates. Investigation results revealed that addition of NAC to refrigerated concentrates prevented platelet activation and reduced the sialidase activity upon rewarming as well as on prolonged storage. Refrigerated concentrates with 50 mM NAC expressed a 23.91 +/- 6.23% of CD62P (P-Selectin) and 22.33 +/- 3.42% of phosphotidylserine (PS), whereas RT-stored platelets showed a 46.87 +/- 5.23% of CD62P and 25.9 +/- 6.48% of phosphotidylserine (PS) after 5 days of storage. Further, key metabolic parameters such as glucose and lactate accumulation indicated reduced metabolic activity. Taken together, investigation and observations indicate that addition of NAC potentially protects refrigerated concentrates by preventing platelet activation, stabilizing sialidase activity, and further reducing the metabolic activity. Hence, we believe that NAC can be a good candidate for an additive solution to retain platelet characteristics during cold storage and may pave the way for extension of storage shelf life. PMID- 26847866 TI - Quality standards, safety and efficacy of blood-derived serum eye drops: A review. AB - Serum eye drops (SEDs) are being used increasingly to treat dry eye syndrome and persistent corneal epithelial defects, and are usually prescribed when conventional treatments fail. SEDs are commonly sourced from the patient's own blood via an autologous collection. Although SEDs are clearly beneficial, they are not available for those patients that cannot donate sufficient blood, and some centres are moving to allogeneic SEDs. Many studies have reported that both allogeneic and autologous SEDs are effective. However, few large randomised controlled trials have been conducted to date, and clinical evidence is therefore limited to smaller studies. Alternatives to serum are also being explored, such as platelet lysate and products made from platelet rich plasma, as they are a rich source of growth factors. This article reviews how some centres are approaching allogeneic collections for SEDs, and alternatives to serum that are currently being explored. PMID- 26847867 TI - Commentary on technical specifications and safety requirements of serum eye drops: Keeping a close eye on the content in cytokines. PMID- 26847868 TI - Health care resource utilization and cost of care for haemophilia A and B patients in Iran. AB - BACKGROUND: Despite the fact that the total therapeutic expenditure of haemophilia is paid by the national health system in Iran, a limited number of research has been performed to evaluate the economic burden of haemophilia. It is even more important when considering the fact that "prophylaxis" has never been used as the main treatment protocol in haemophiliacs in the country, causing high arthropathy rates. The aim of this study is to evaluate the cost drivers in the treatment of haemophilia A and B patients in Iran. METHODS: The national registry database of Ministry of Health (MoH) was queried to identify total number of individuals characteristics diagnosed with Factor VIII and IX deficiency. The service package defined by the department for special diseases was used as the reference for the type and frequency of health care utilization in haemophiliacs in Iran. The direct medical costs including prescription, medical intervention, inpatient, outpatient and diagnostics services and arthroplasty were considered. The prices were extracted from Iranian medical tariff book 2014-15. Medication cost was obtained from the Iranian Food and Drug Organization. RESULTS: Among 8,337 patients registered with bleeding disorders, 3,948 and 848 were identified with haemophilia A and B respectively, of whom 856 (18%) patients had inhibitor at any time in the past. In the two groups, 2,328 (59%) and 452 (53%) patients suffered from severe, 686 (17%) and 186 (22%) from moderate and 902 (23%) and 185 (22%) from mild type of haemophilia. The average annual health care cost for every patient was USD 15,130, mostly allocated to medication USD 10,180 (67%), followed by therapeutic services USD 4,775 (32%) while diagnostic services stood third USD 177 (1%). CONCLUSIONS: There is an urgent need for developing clinical practice guidelines for treatment protocols, procedures and supportive care in haemophilia management in Iran. PMID- 26847869 TI - Investigation of the Transition from Local Anodic Oxidation to Electrical Breakdown During Nanoscale Atomic Force Microscopy Electric Lithography of Highly Oriented Pyrolytic Graphite. AB - As one of the tip-based top-down nanoscale machining methods, atomic force microscopy (AFM) electric lithography is capable of directly generating flexible nanostructures on conductive or semi-conductive sample surfaces. In this work, distinct fabrication mechanisms and mechanism transition from local anodic oxidation (LAO) to electrical breakdown (BD) in the AFM nanoscale electric lithography of the highly oriented pyrolytic graphite sample surface was studied. We provide direct evidence of the transition process mechanism through the detected current-voltage (I-V) curve. Characteristics of the fabrication results under the LAO, transition, and BD regions involving the oxide growth rate or material removal rate and AFM probe wear are analyzed in detail. These factors are of great significance for improving the machining controllability and expanding its potential applications. PMID- 26847870 TI - Relation of exposure to amino acids involved in sarcosine metabolic pathway on behavior of non-tumor and malignant prostatic cell lines. AB - BACKGROUND: Sarcosine (N-methylglycine) was previously delineated as a substantial oncometabolite of prostate cancer (PCa) and its metabolism seems to be significantly involved in PCa development and behavior. METHODS: We focused on investigation whether the exposure of prostate cells (PNT1A, 22Rv1, and PC-3) to sarcosine-related amino acids (glycine, dimethylglycine, and sarcosine) affects their aggressiveness (cell mobility and division rates, using real-time cell based assay). The effect of supplementation on expression of glycine-N methyltransferase (GNMT) mRNA was examined using qRT-PCR. Finally, post-treatment amino acids patterns were determined with consequent statistical processing using the Ward's method, factorial ANOVA and principal component analysis (P < 0.05). RESULTS: The highest migration induced sarcosine and glycine in metastatic PC-3 cells (a decrease in relative free area about 53% and 73%). The highest cell division was achieved after treatment of 22Rv1 and PC-3 cells with sarcosine (time required for division decreased by 65% or 45%, when compared to untreated cells). qRT-PCR revealed also significant effects on expression of GNMT. Finally, amino acid profiling shown specific amino acid patterns for each cell line. In both, treated and untreated PC-3 cells significantly higher levels of serine, glutamic acid, and aspartate, linked with prostate cancer progression were found. CONCLUSIONS: Sarcosine-related amino acids can exceptionally affect the behavior of benign and malignant prostate cells. PMID- 26847872 TI - Tryptamine-Based Derivatives as Transient Receptor Potential Melastatin Type 8 (TRPM8) Channel Modulators. AB - Pharmacological modulation of the transient receptor potential melastatin type 8 (TRPM8) is currently under investigation as a new approach for the treatment of pain and other diseases. In this study, a series of N-substituted tryptamines was prepared to explore the structural requirements determining TRPM8 modulation. Using a fluorescence-based screening assay, we identified two compounds acting as an activator (2-(1H-indol-3-yl)-N-(4-phenoxybenzyl)ethanamine, 21) or an inhibitor (N,N-dibenzyl-2-(1H-indol-3-yl)ethanamine, 12) of calcium influx in HEK293 cells. In patch-clamp recordings, compound 21 displayed a significantly higher potency (EC50 = 40 +/- 4 MUM) and a similar efficacy when compared to menthol; by contrast, compound 12 produced a concentration-dependent inhibition of menthol-induced TRPM8 currents (IC50 = 367 +/- 24 nM). Molecular modeling studies using a homology model of a single rat TRPM8 subunit identified a putative binding site located between the VSD and the TRP box, disclosing differences in the binding modes for the agonist and the antagonist. PMID- 26847873 TI - Bioanalytical challenges and improved detection of circulating levels of IL-13. AB - BACKGROUND: IL-13 is a key mediator of type 2 inflammation-driven diseases. Circulating IL-13 levels are very low and challenging to detect reliably. We assessed the ability of immunoassays on the Erenna((r)) and IMPACT platforms to measure serum IL-13 in asthma, idiopathic pulmonary fibrosis (IPF) and atopic dermatitis (AD) patients and in healthy controls (HC). RESULTS: The Erenna IL-13 assay exhibited significant specificity issues and had limited ability to detect IL-13 in serum samples. The IMPACT IL-13 assay had excellent specificity and detected IL-13 in 100% of serum samples tested from asthma, IPF and AD patients and HC. Serum IL-13 levels were significantly elevated in asthma, IPF and AD patients, relative to HC. CONCLUSION: The IMPACT IL-13 assay had fg/ml sensitivity and excellent specificity, enabling reliable detection of circulating levels of IL-13. PMID- 26847871 TI - Histone H4 acetylation and the epigenetic reader Brd4 are critical regulators of pluripotency in embryonic stem cells. AB - BACKGROUND: Pluripotent cells can be differentiated into many different cell types in vitro. Successful differentiation is guided in large part by epigenetic reprogramming and regulation of critical gene expression patterns. Recent genome wide studies have identified the distribution of different histone-post translational modifications (PTMs) in various conditions and during cellular differentiation. However, our understanding of the abundance of histone PTMs and their regulatory mechanisms still remain unknown. RESULTS: Here, we present a quantitative and comprehensive study of the abundance levels of histone PTMs during the differentiation of mouse embryonic stem cells (ESCs) using mass spectrometry (MS). We observed dynamic changes of histone PTMs including increased H3K9 methylation levels in agreement with previously reported results. More importantly, we found a global decrease of multiply acetylated histone H4 peptides. Brd4 targets acetylated H4 with a strong affinity to multiply modified H4 acetylation sites. We observed that the protein levels of Brd4 decreased upon differentiation together with global histone H4 acetylation. Inhibition of Brd4:histone H4 interaction by the BET domain inhibitor (+)-JQ1 in ESCs results in enhanced differentiation to the endodermal lineage, by disrupting the protein abundance dynamics. Genome-wide ChIP-seq mapping showed that Brd4 and H4 acetylation are co-occupied in the genome, upstream of core pluripotency genes such as Oct4 and Nanog in ESCs and lineage-specific genes in embryoid bodies (EBs). CONCLUSIONS: Together, our data demonstrate the fundamental role of Brd4 in monitoring cell differentiation through its interaction with acetylated histone marks and disruption of Brd4 may cause aberrant differentiation. PMID- 26847874 TI - Effect of Emergency Medical Services Use on Hospital Outcomes of Acute Hemorrhagic Stroke. AB - BACKGROUND: It is unclear whether the use of emergency medical services (EMS) is associated with enhanced survival and decreased disability after hemorrhagic stroke and whether the effect size of EMS use differs according to the length of stay (LOS) in emergency department (ED). METHODS: Adult patients (19 years and older) with acute hemorrhagic stroke who survived to admission at 29 hospitals between 2008 and 2011 were analyzed, excluding those who had symptom-to-ED arrival time of 3 h or greater, received thrombolysis or craniotomy before inter hospital transfer, or had experienced cardiac arrest, had unknown information about ambulance use and outcomes. Exposure variable was EMS use. Endpoints were survival at discharge and worsened modified Rankin Scale (W-MRS) defined as 3 or greater points difference between pre- and post-event MRS. Adjusted odds ratios (AORs) with 95% confidence intervals (95% CIs) for the outcomes were calculated, including potential confounders (demographic, socioeconomic status, clinical parameter, comorbidity, behavior, and time of event) in the final model and stratifying patients by inter-hospital transfer and by time interval from symptom to ED arrival (S2D). ED LOS, classified into short (<120 min) and long (>=120 min), was added to the final model for testing of the interaction model. RESULTS: A total of 2,095 hemorrhagic strokes were analyzed in which 75.6% were transported by EMS. For outcome measures, 17.4% and 41.4% were dead and had worsened MRS, respectively. AORs (95% CIs) of EMS were 0.67 (0.51-0.89) for death and 0.74 (0.59-0.92) for W-MRS in all patients. The effect size of EMS, however, was different according to LOS in ED. AORs (95% CIs) for death were 0.74 (0.54 1.01) in short LOS and 0.60 (0.44-0.83) in long LOS group. AORs (95% CIs) for W MRS were 0.76 (0.60-0.97) in short LOS and 0.68 (0.52-0.88) in long LOS group. CONCLUSIONS: EMS transport was associated with lower hospital mortality and disability after acute hemorrhagic stroke. Effect size of EMS use for mortality was significant in patients with long ED LOS. Key words: emergency medical service; hemorrhagic stroke; mortality; disability. PMID- 26847875 TI - Caveolin-1 is upregulated in hepatic stellate cells but not sinusoidal endothelial cells after liver injury. AB - Sinusoidal endothelial cells (SEC) and hepatic stellate cells (HSC) are closely associated specialized vascular cells residing in the hepatic sinusoid. These cells have been shown to play important roles in many different pathophysiologic processes, in particular in liver fibrosis/cirrhosis and portal hypertension. Caveolin-1 functions as a scaffolding protein, and has a variety of functions including in many disease states, such as liver cirrhosis. Although previous studies have shown that in the injured rat liver, caveolin-1 is upregulated, the precise cells in which remains unclear. Therefore, the purpose of this study was to clarify the cell type (or types) in which caveolin-1 is expressed in normal and injured rat liver. We have utilized both detailed immunohistochemical labeling with cell specific markers as well as cell isolation techniques (isolating sinusoidal endothelial cells, HSCs, and hepatocytes) in normal and injured (bile duct ligation) rat liver. We show here that in the normal liver caveolin-1 is expressed predominantly in HSCs and SECs but after liver injury there is upregulation of caveolin-1 in HSCs, but not in SECs. These data have functional implications for the cells in which caveolin-1 is regulated. PMID- 26847876 TI - Oncology Pathways-Preventing a Good Idea From Going Bad. PMID- 26847877 TI - Self-organization of frozen light in near-zero-index media with cubic nonlinearity. AB - Optical beams are generally unbound in bulk media, and propagate with a velocity approximately amounting to the speed of light in free-space. Guidance and full spatial confinement of light are usually achieved by means of waveguides, mirrors, resonators, and photonic crystals. Here we theoretically demonstrate that nonlinear self-organization can be exploited to freeze optical beams in bulk near-zero-index media, thus enabling three-dimensional self-trapping of still light without the need of optical resonators. Light is stopped to a standstill owing to the divergent wavelength and the vanishing group velocity, effectively rendering, through nonlinearity, a positive-epsilon trapping cavity carved in an otherwise slightly-negative-epsilon medium. By numerically solving Maxwell's equations, we find a soliton-like family of still azimuthal doughnuts, which we further study through an adiabatic perturbative theory that describes soliton evaporation in lossy media or condensation in actively pumped materials. Our results suggest applications in optical data processing and storage, quantum optical memories, and soliton-based lasers without cavities. Additionally, near zero-index conditions can also be found in the interplanetary medium and in the atmosphere, where we provide a complementary explanation to the rare phenomenon of ball-lightning. PMID- 26847878 TI - Molecular Engineering Combined with Cosensitization Leads to Record Photovoltaic Efficiency for Non-ruthenium Solar Cells. AB - Here comes the sun: By using a combined strategy of molecular engineering and cosensitization, impressively high Jsc and Voc values were achieved for porphyrin dyes, resulting in high photovoltaic efficiencies up to 11.5 %, a record for non ruthenium dye-sensitized solar cells (DSSCs) with the I(-) /I3 (-) electrolyte. The results provide insight into furthering the development of efficient DSSCs through synergistically enhanced photovoltage and photocurrent. PMID- 26847880 TI - A word from the parting editor, 4760 pages down the line. PMID- 26847879 TI - Salt-induced aggregation of gold nanoparticles for photoacoustic imaging and photothermal therapy of cancer. AB - The challenge in photothermal therapy (PTT) is to develop biocompatible photothermal transducers that can absorb and convert near-infrared (NIR) light into heat with high efficiency. Herein, we report salt-induced aggregation of gold nanoparticles (GNPs) in biological media to form highly efficient and biocompatible NIR photothermal transducers for PTT and photothermal/photoacoustic (PT/PA) imaging of cancer. The GNP depots in situ formed by salt-induced aggregation of GNPs show strong NIR absorption induced by plasmonic coupling between adjacent GNPs and very high photothermal conversion efficiency (52%), enabling photothermal destruction of tumor cells. More interestingly, GNPs in situ aggregate in tumors to form GNP depots, enabling simultaneous PT/PA imaging and PTT of the tumors. These findings may provide a simple and effective way to develop a new class of intelligent and biocompatible NIR photothermal transducers with high efficiency for PT/PA imaging and PTT. PMID- 26847882 TI - Draft Genome Sequence of Altererythrobacter marensis DSM 21428T, Isolated from Seawater. AB - Altererythrobacter marensis DSM 21428(T) was isolated from seawater collected around Mara Island, South Korea. The genomic characteristics of this strain support its potential for alkane-related compound degradation. A. marensis DSM 21428(T) has potential applications in bioremediation projects concerning offshore petroleum spill prevention and response. PMID- 26847883 TI - Draft Genome Sequence of a Pseudomonas aeruginosa Strain Able To Decompose N,N Dimethyl Formamide. AB - Pseudomonas aeruginosa is a Gram-negative bacterium, which uses a variety of organic chemicals as carbon sources. Here, we report the genome sequence of the Cu1510 isolate from wastewater containing a high concentration of N,N-dimethyl formamide. PMID- 26847884 TI - Draft Genome Sequence of Oceanobacillus picturae Heshi-B3, Isolated from Fermented Rice Bran in a Traditional Japanese Seafood Dish. AB - Oceanobacillus picturae strain Heshi-B3 was isolated from rice bran in a traditional fermented seafood dish named Heshiko, which was produced in Fukui Prefecture in Japan. Here, we report the draft genome sequence of O. picturae strain Heshi B-3. PMID- 26847885 TI - Complete Genome Sequence of the WHO International Standard for HIV-2 RNA Determined by Deep Sequencing. AB - The World Health Organization (WHO) International Standard for HIV-2 RNA nucleic acid assays was characterized by complete genome deep sequencing. The entire coding sequence and flanking long terminal repeats (LTRs), including minority species, were assigned subtype A. This information will aid design, development, and evaluation of HIV-2 RNA amplification assays. PMID- 26847886 TI - Complete Genome Sequence of Streptococcus salivarius HSISS4, a Human Commensal Bacterium Highly Prevalent in the Digestive Tract. AB - The human commensal bacterium Streptococcus salivarius plays a major role in the equilibrium of microbial communities of the digestive tract. Here, we report the first complete genome sequence of a Streptococcus salivarius strain isolated from the small intestine, namely, HSISS4. Its circular chromosome comprises 1,903 coding sequences and 2,100,988 nucleotides. PMID- 26847887 TI - Draft Whole-Genome Sequence of Haemophilus ducreyi Strain AUSPNG1, Isolated from a Cutaneous Ulcer of a Child from Papua New Guinea. AB - Haemophilus ducreyi has recently emerged as a leading cause of cutaneous ulcers in the yaws-endemic areas of Papua New Guinea and other South Pacific islands. Here, we report the draft genome sequence of the H. ducreyi strain AUSPNG1, isolated from a cutaneous ulcer of a child from Papua New Guinea. PMID- 26847888 TI - A Spontaneous Deletion of the US1.67/US2 Genomic Region on the Bovine Herpesvirus 1 Strain Cooper. AB - Bovine herpesvirus 1 (BoHV-1) is an alphaherpesvirus with a genome of 135 kb. Some BoHV-1 genes are nonessential and may be deleted from the viral genome. Here, a spontaneous gene deletion was identified in the BoHV-1 strain Cooper. Genes of the US1.67/US2 region were absent, as determined by next-generation sequencing. PMID- 26847889 TI - Genome Sequence of Acidovorax avenae Strain T10_61 Associated with Sugarcane Red Stripe in Argentina. AB - Red stripe of sugarcane in Argentina is a bacterial disease caused by Acidovorax avenae. The genome sequence from the first isolate of this bacterium in Argentina is presented here. The draft genome of the A. avenae T10_61 strain contains 5,646,552 bp and has a G+C content of 68.6 mol%. PMID- 26847891 TI - Complete Closed Genome Sequences of Salmonella enterica subsp. enterica Serotypes Anatum, Montevideo, Typhimurium, and Newport, Isolated from Beef, Cattle, and Humans. AB - Salmonella enterica spp. are a diverse group of bacteria with a wide range of virulence potential. To facilitate genome comparisons across this virulence spectrum, we present eight complete closed genome sequences of four S. enterica serotypes (Anatum, Montevideo, Typhimurium, and Newport), isolated from various cattle samples and from humans. PMID- 26847890 TI - Draft Genome Sequence of Coccoid Lactobacillus equigenerosi NRIC 0697T Isolated from the Gastrointestinal Tracts of Healthy Thoroughbreds. AB - Lactobacillus equigenerosi NRIC 0697(T) was isolated from the gastrointestinal tracts of healthy thoroughbreds. This strain produced unique spherical or oval cells, which is rare in the genus Lactobacillus. Here, we report the draft genome sequence of this strain. PMID- 26847892 TI - Draft Genome Sequence of Actinomyces odontolyticus subsp. actinosynbacter Strain XH001, the Basibiont of an Oral TM7 Epibiont. AB - Here, we present the draft genome sequence of Actinomyces odontolyticus subsp. actinosynbacter strain XH001, isolated from the human oral cavity. Uniquely, it was discovered as a host bacterium to the ultrasmall epibiont TM7x, which is the first cultivated member of "Candidatus Saccharibacteria" (formerly candidate phylum TM7). PMID- 26847893 TI - Draft Genome Sequence of Bacillus cecembensis PN5T (DSM 21993), a Psychrotolerant Bacterium Isolated from Soil Samples near the Pindari Glacier. AB - Bacillus cecembensis PN5(T) is a Gram-positive, aerobic, and spore-forming bacterium with very high intrinsic heat resistance. Here, we report the 4.72-Mb draft genome sequence of B. cecembensis PN5(T), the first genome sequence of this species, which will promote its fundamental research. PMID- 26847895 TI - Draft Genome Sequence of Bacillus shackletonii LMG 18435T, Isolated from Volcanic Mossy Soil. AB - Bacillus shackletonii LMG 18435(T) is a Gram-positive, aerobic, and spore-forming bacterium. Here, we report the 5.30-Mb draft genome sequence of B. shackletonii LMG 18435(T), which will promote its fundamental research and provide useful information for genomic taxonomy and phylogenomics of Bacillus-like bacteria. PMID- 26847894 TI - Draft Genome Sequence of Brevibacillus choshinensis HPD52T (DSM 8552), a Bacterial Host for Efficient Expression of Heterologous Proteins. AB - Brevibacillus choshinensis HPD52(T) (DSM 8552) is a Gram-positive, spore-forming, and protein-producing bacterium. Here, we report the 6.28-Mb draft genome sequence of B. choshinensis HPD52(T), which will promote its application and provide useful information for genomic taxonomy and phylogenomics of Bacillus like bacteria. PMID- 26847896 TI - Draft Genome Sequence of Bacillus plakortidis P203T (DSM 19153), an Alkali- and Salt-Tolerant Marine Bacterium. AB - Bacillus plakortidis P203(T) is a Gram-positive, spore-forming, and alkali- and salt-tolerant marine bacterium. Here, we report the 3.97-Mb draft genome sequence of B. plakortidis P203(T), which will promote its fundamental research and provide useful information for genomic taxonomy and phylogenomics of Bacillus like bacteria. PMID- 26847897 TI - Draft Genome Sequence of Bacillus muralis LMG 20238T (DSM 16288), a Spore-Forming Bacterium Isolated from Deteriorated Mural Paintings. AB - Bacillus muralis LMG 20238(T) is a Gram-positive, aerobic, and spore-forming bacterium. Here, we report the 5.18-Mb draft genome sequence of B. muralis LMG 20238(T), which is the first genome sequence of this species and will promote its fundamental research. PMID- 26847898 TI - Draft Genome Sequence of Bacillus humi LMG 22167T (DSM 16318), an Endospore Forming Bacterium Isolated from Soil. AB - Bacillus humi LMG 22167(T) is a Gram-positive, aerobic, and spore-forming bacterium Here, we report the 4.80-Mb draft genome sequence of B. humi LMG 22167(T), which is the first genome sequence of this species and will promote its fundamental research. PMID- 26847899 TI - Draft Genome Sequences of Sarcina ventriculi Strains Isolated from Wild Japanese Macaques in Yakushima Island. AB - We report the draft genome sequences of Sarcina ventriculi strains 14 and 17, both isolated from feces of wild Yakushima macaques (Macaca fuscata yakui). These genomic sequences will be helpful for the phylogenetic consideration of the family Clostridiaceae and understanding of the contribution of intestinal microbiota to the survival of Yakushima macaques. PMID- 26847900 TI - Whole-Genome Sequencing Reveals a New Genospecies of Methylobacterium sp. GXS13, Isolated from Vitis vinifera L. Xylem Sap. AB - The whole-genome sequence of a new genospecies of Methylobacterium sp., named GXS13 and isolated from grapevine xylem sap, is reported and demonstrates potential for methylotrophy, cytokinin synthesis, and cell wall modification. In addition, biosynthetic gene clusters were identified for cupriachelin, carotenoid, and acyl-homoserine lactone using the antiSMASH server. PMID- 26847901 TI - Complete Genome Sequence of a Genotype XVII Newcastle Disease Virus, Isolated from an Apparently Healthy Domestic Duck in Nigeria. AB - The first complete genome sequence of a strain of Newcastle disease virus (NDV) of genotype XVII is described here. A velogenic strain (duck/Nigeria/903/KUDU 113/1992) was isolated from an apparently healthy free-roaming domestic duck sampled in Kuru, Nigeria, in 1992. Phylogenetic analysis of the fusion protein gene and complete genome classified the isolate as a member of NDV class II, genotype XVII. PMID- 26847902 TI - Draft Genome Sequence of Mycobacterium tuberculosis KT-0204, Isolated in South Korea. AB - Here, we describe the draft genome sequence of Mycobacterium tuberculosis KT 0204, non-Beijing family. This sequence will reveal genes related to the evolution and adaptation of M. tuberculosis KT-0204 in human hosts. PMID- 26847903 TI - Complete Genomic Sequence of Maize Rough Dwarf Virus, a Fijivirus Transmitted by the Small Brown Planthopper. AB - The nucleotide sequences of the 10 genomic segments of an Italian isolate of maize rough dwarf virus (MRDV) were determined. This first complete genomic sequence of MRDV will help understand the phylogenetic relationships among group 2 fijiviruses and especially the closely related rice black-streaked dwarf virus, which is also found to naturally infect maize. PMID- 26847904 TI - Genome Sequence of Mycobacteriophage Cabrinians. AB - Mycobacteriophage Cabrinians is a newly isolated phage capable of infecting both Mycobacterium phlei and Mycobacterium smegmatis and was recovered from a soil sample in New York City, NY. Cabrinians has a genome length of 56,669 bp, encodes 101 predicted proteins, and is a member of mycobacteriophages in cluster F. PMID- 26847905 TI - Two Complete Genome Sequences of Phasey Bean Mild Yellows Virus, a Novel Member of the Luteoviridae from Australia. AB - We present here the complete genome sequences of a novel polerovirus from Trifolium subterraneum (subterranean clover) and Cicer arietinum (chickpea) and compare these to a partial viral genome sequence obtained from Macroptilium lathyroides (phasey bean). We propose the name phasey bean mild yellows virus for this novel polerovirus. PMID- 26847906 TI - Draft Genome Sequence of Lactococcus lactis subsp. lactis bv. diacetylactis CRL264, a Citrate-Fermenting Strain. AB - We report the draft genome sequence of Lactococcus lactis subsp. lactis bv. diacetylactis CRL264, a natural strain isolated from artisanal cheese from northwest Argentina. L. lactis subsp. lactis bv. diacetylactis is one of the most important microorganisms used as starter culture around the world. The CRL264 strain constitutes a model microorganism in the studies on the generation of aroma compounds (diacetyl, acetoin, and 2,3-butanediol) by lactic acid bacteria. Our genome analysis shows similar genetic organization to other available genomes of L. lactis bv. diacetylactis strains. PMID- 26847908 TI - Draft Genome Sequence of Caloramator mitchellensis, a Thermoanaerobe Isolated from the Waters of the Great Artesian Basin. AB - The genome sequence of Caloramator mitchellensis strain VF08, a rod-shaped, heterotrophic, strictly anaerobic bacterium isolated from the free-flowing waters of a Great Artesian Basin (GAB) bore well located in Mitchell, an outback Queensland town in Australia, is reported here. The analysis of the 2.42-Mb genome sequence indicates that the attributes of the genome are consistent with its physiological and phenotypic traits. PMID- 26847907 TI - Draft Genome Sequences of Four Enterococcus faecium Strains Isolated from Argentine Cheese. AB - We report the draft genome sequences of four Enterococcus faecium strains isolated from Argentine regional cheeses. These strains were selected based on their technological properties, i.e., their ability to produce aroma compounds (diacetyl, acetoin, and 2,3-butanediol) from citrate. The goal of our study is to provide further genetic evidence for the rational selection of enterococci strains based on their pheno- and genotype in order to be used in cheese production. PMID- 26847909 TI - Draft Genome of Debaryomyces fabryi CBS 789T, Isolated from a Human Interdigital Mycotic Lesion. AB - The yeast genus Debaryomyces comprises species isolated from various natural habitats, man-made environments, and clinical materials. Here, the draft genome of D. fabryi CBS 789(T), isolated from a human interdigital mycotic lesion, is presented. PMID- 26847911 TI - [PentaRay catheter in persistent atrial fibrillation ablation]. PMID- 26847912 TI - Associations between Meal and Snack Frequency and Diet Quality in US Adults: National Health and Nutrition Examination Survey 2003-2012. AB - BACKGROUND: The associations between eating frequency and diet quality are inconclusive, which might be a result of different effects of meal frequency and snack frequency. OBJECTIVE: This cross-sectional study examined the associations of eating frequency, meal frequency, and snack frequency with diet quality, based on data from the National Health and Nutrition Examination Survey 2003-2012. DESIGN: Dietary intake was assessed in 19,427 US adults aged 20 years or older, using two 24-hour dietary recalls. All eating occasions providing >=50 kcal were divided into either meals or snacks on the basis of contribution to daily energy intake (>=15% or <15%), self-report, and time (6 am to 10 am, 12 pm to 3 pm, and 6 pm 9 pm or others). Diet quality was assessed using the Healthy Eating Index 2010 (HEI-2010). STATISTICAL ANALYSES PERFORMED: Linear regression analyses were performed to explore the associations of eating frequency, meal frequency, and snack frequency (independent variables) with dietary intake variables (dependent variables). RESULTS: Higher eating frequency was modestly and positively associated with higher HEI-2010 in both men and women; one additional eating occasion per day increased HEI-2010 by 1.77 points in men and 2.22 points in women (both P<0.0001). All measures of meal frequency and snack frequency were also modestly and positively associated with HEI-2010 in both sexes, irrespective of the definition of meals and snacks. However, the associations were stronger for meal frequency than for snack frequency; one additional meal per day increased HEI-2010 by 2.14 to 5.35 points, and one additional snack per day increased HEI-2010 by 1.25 to 1.97 points (all P<0.0001). CONCLUSIONS: In a representative sample of US adults, both meal frequency and snack frequency were modestly associated with better diet quality. PMID- 26847910 TI - Repertaxin, an inhibitor of the chemokine receptors CXCR1 and CXCR2, inhibits malignant behavior of human gastric cancer MKN45 cells in vitro and in vivo and enhances efficacy of 5-fluorouracil. AB - Chemokine-mediated activation of G protein-coupled receptors CXCR1/2 promotes tumor growth, invasion, inflammation and metastasis. Repertaxin, a CXCR1/2 small molecule inhibitor, has been shown to attenuate many of these tumor-associated processes. The present study aimed to investigate the effects of repertaxin alone and in combination with 5-fluorouracil (5-FU) on the malignant behavior of gastric cancer and the potential mechanisms. Gastric cancer MKN45 cells were treated in vitro with repertaxin and 5-FU, either alone or in combination. MTT and colony formation assay were performed to assess proliferation. Cell cycle progression and apoptosis was completed by flow cytometry. Migration and invasion were also assessed by transwell and wound-healing assay. Western blot analysis and quantitative RT-PCR were performed to determine expression of signaling molecules. MKN45 cells were also grown as xenografts in nude mice. Mice were treated with repertaxin and 5-FU, and tumor volume and weight, angiogenesis, proliferation and apoptosis were monitored. Combination of repertaxin and 5-FU inhibited MKN45 cell proliferation and increased apoptosis better than either agent alone. Similarly, enhanced effect of the combination was also observed in migration and invasion assays. The improved effect of repertaxin and 5-FU was also observed in vivo, as xenograft models treated with both compounds exhibited significantly decreased tumor volume and increased apoptosis. In conclusion, repertaxin inhibited malignant behavior of human gastric cancer MKN45 cells in vitro and in vivo and enhances efficacy of 5-fluorouracil. These data provide rationale that targeting CXCR1/2 with small molecule inhibitors may enhance chemotherapeutic efficacy for the treatment of gastric cancer. PMID- 26847913 TI - The effects of acute lipopolysaccharide challenge on dairy goat liver metabolism assessed with 1 HNMR metabonomics. AB - We investigated the mechanisms mediating hepatic metabolic responses to an acute lipopolysaccharide (LPS) challenge in goats. Guanzhong dairy goats (15) were randomly divided into three groups: control (CTL, saline, 0.2 ml/kg BW), lower dose LPS (LPS-L, 20 MUg/kg BW) and higher dose LPS (LPS-H, 40 MUg/kg BW). All injections were administered intraperitoneally twice with a 24-h interval. Forty eight hours after the first injection, blood samples were collected to extract plasma for biochemical analysis, and liver tissues were biopsied and stored in liquid nitrogen for metabonomics analysis. We found that plasma levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin increased (p < 0.05) in both LPS-treated groups, whereas plasma triglyceride, cholesterol, very low-density lipoprotein, low-density lipoprotein, high-density lipoprotein, total protein and albumin levels markedly decreased (p < 0.05). The increased activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL) 1beta, IL-6 and IL-8 indicated hepatic injury and metabolic dysfunction in some degree. Using proton nuclear magnetic resonance (1 H-NMR) metabonomics and the Chenomx NMR suite database, 69 metabolites were detected and identified. Metabolic differences among the groups were determined with pattern recognition analyses using principal component analysis and supervised projection to latent structures discriminant analysis. Pattern recognition analysis distinguished and clustered the metabolite variables from the three groups, finding nine of 69 metabolites that differed significantly between two of the three groups: six from the LPS-L or LPS-H groups differed from CTL and three differed between LPS-L and LPS-H groups. These altered metabolites were closely connected with glucose, lipid and amino acid metabolic pathways in hepatocytes. Based on an analysis of these metabolites and their relevant pathways, the mechanisms and degree of hepatic injury were deduced. Therefore, the metabolic profile was used effectively to detect characteristic hepatic metabolites, discriminate metabolic changes induced by LPS, clarify the mechanisms for the resulting metabolic dysfunctions and provide efficient information to diagnose liver injury. PMID- 26847914 TI - Formation mechanism and biological activity of novel thiolated human-like collagen iron complex. AB - To develop an iron supplement that is effectively absorbed and utilized, thiolated human-like collagen was created to improve the iron binding capacity of human-like collagen. A thiolated human-like collagen-iron complex was prepared in a phosphate buffer, and one mole of thiolated human-like collagen-iron possessed approximately 28.83 moles of iron. The characteristics of thiolated human-like collagen-iron were investigated by ultraviolet-visible absorption spectroscopy, Fourier transform infrared spectroscopy, circular dichroism, and differential scanning calorimetry. The results showed that the thiolated human-like collagen iron complex retained the secondary structure of human-like collagen and had greater thermodynamic stability than human-like collagen, although interactions between iron ions and human-like collagen occurred during the formation of the complex. In addition, to evaluate the bioavailability of thiolated human-like collagen-iron, an in vitro Caco-2 cell model and an in vivo iron deficiency anemia mouse model were employed. The data demonstrated that the thiolated human like collagen-iron complex exhibited greater bioavailability and was more easily utilized than FeSO4, ferric ammonium citrate, or ferrous glycinate. These results indicated that the thiolated human-like collagen-iron complex is a potential iron supplement in the biomedical field. PMID- 26847915 TI - Antibiotic-eluting hydrophilized PMMA bone cement with prolonged bactericidal effect for the treatment of osteomyelitis. AB - Osteomyelitis is still considered to be one of the major challenges for orthopedic surgeons despite advanced antiseptic surgical procedures and pharmaceutical therapeutics. In this study, hydrophilized poly(methyl methacrylate) (PMMA) bone cements containing Pluronic F68 (EG79PG28EG79) as a hydrophilic additive and vancomycin (F68-VAcements) were prepared to allow the sustained release of the antibiotic for adequate periods of time without any significant loss of mechanical properties. The compressive strengths of the bone cements with Pluronic F68 compositions less than 7 wt% were not significantly different compared with the control vancomycin-loaded bone cement (VAcement). TheF68 (7 wt%)-VAcement showed sustained release of the antibiotic for up to 11 weeks and almost 100% release from the bone cement. It also prohibited the growth ofS. aureus(zone of inhibition) over six weeks (the required period to treat osteomyelitis), and it did not show any notable cytotoxicity. From an animal study using a femoral osteomyelitis rat model, it was observed that theF68 (7 wt%)-VAcement was effective for the treatment of osteomyelitis, probably as a result of the prolonged release of antibiotic from the PMMA bone cement. On the basis of these findings, it can be suggested that the use of Pluronic F68 as a hydrophilic additive for antibiotic-eluting PMMA bone cement can be a promising strategy for the treatment of osteomyelitis. PMID- 26847916 TI - MicroRNA-21 expression is associated with the clinical features of patients with gastric carcinoma and affects the proliferation, invasion and migration of gastric cancer cells by regulating Noxa. AB - The expression levels of microRNA-21 (miR-21) are increased in a number of types of solid tumors. However, the association between miR-21 expression and clinical features of patients with gastric carcinoma, and gastric cancer proliferation, invasion and migration remains to be elucidated. The present study investigated the effect of miR-21 on the clinical features, proliferation, invasion and migration of gastric cancer and the underlying mechanisms associated with Noxa. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed to detect the expression levels of miR-21 and Noxa in samples of gastric cancer tissue and matched, adjacent, non-tumor tissue. The association between miR-21 expression and the clinical features of patients with gastric carcinoma, as well as the correlation between the mRNA and protein expression levels of miR-21 and Noxa were analyzed. SGC-7901 gastric cancer cells were cultured in vitro and transfected with an miR-21 mimic. The effect of miR-21 upregulation on proliferation and the cell cycle was determined using the MTT assay and flow cytometry. In addition, migration and invasion of SGC-7901 cells were observed using the Transwell assay. The target gene of miR-21 was identified using bioinformatics software and a dual luciferase reporting system. The effect of miR-21 upregulation on Noxa expression levels in SGC-7901 cells was also analyzed by RT-qPCR and western blotting. Increased levels of miR-21 expression and decreased levels of Noxa expression were observed in gastric cancer tissue samples when compared with the adjacent non-tumor tissue samples. An increased miR-21 expression level was identified as a risk factor for advanced stage gastric cancer, lymph node metastasis and larger primary tumors. Furthermore, the overexpression of miR-21 inhibited Noxa expression levels in SGC-7901 cells. Therefore, high levels of miR-21 expression may induce gastric cancer migration and invasion via the downregulation of Noxa expression. PMID- 26847917 TI - Cardiopulmonary bypass increases pulmonary microvascular permeability through the Src kinase pathway: Involvement of caveolin-1 and vascular endothelial cadherin. AB - Changes in pulmonary microvascular permeability following cardiopulmonary bypass (CPB) and the underlying mechanisms have not yet been established. Therefore, the aim of the present study was to elucidate the alterations in pulmonary microvascular permeability following CPB and the underlying mechanism. The pulmonary microvascular permeability was measured using Evans Blue dye (EBD) exclusion, and the neutrophil infiltration and proinflammatory cytokine secretion was investigated. In addition, the activation of Src kinase and the phosphorylation of caveolin-1 and vascular endothelial cadherin (VE-cadherin) was examined. The results revealed that CPB increased pulmonary microvascular leakage, neutrophil count and proinflammatory cytokines in the bronchoalveolar lavage fluid, and activated Src kinase. The administration of PP2, an inhibitor of Src kinase, decreased the activation of Src kinase and attenuated the increase in pulmonary microvascular permeability observed following CPB. Two important proteins associated with vascular permeability, caveolin-1 and VE-cadherin, were significantly activated at 24 h in the lung tissues following CPB, which correlated with the alterations in pulmonary microvascular permeability and Src kinase. PP2 administration inhibited their activation, suggesting that they are downstream factors of Src kinase activation. The data indicated that the Src kinase pathway increased pulmonary microvascular permeability following CPB, and the activation of caveolin-1 and VE-cadherin may be involved. Inhibition of this pathway may provide a potential therapy for acute lung injury following cardiac surgery. PMID- 26847918 TI - Development and Validation of a High-Performance Thin-Layer Chromatographic Method for the Simultaneous Determination of Two Binary Mixtures Containing Ketorolac Tromethamine with Phenylephrine Hydrochloride and with Febuxostat. AB - A validated and highly selective high-performance thin-layer chromatography (HPTLC) method was developed for the determination of ketorolac tromethamine (KTC) with phenylephrine hydrochloride (PHE) (Mixture 1) and with febuxostat (FBX) (Mixture 2) in bulk drug and in combined dosage forms. The proposed method was based on HPTLC separation of the drugs followed by densitometric measurements of their spots at 273 and 320 nm for Mixtures 1 and 2, respectively. The separation was carried out on Merck HPTLC aluminum sheets of silica gel 60 F254 using chloroform-methanol-ammonia (7:3:0.1, v/v) and (7.5:2.5:0.1, v/v) as mobile phase for KTC/PHE and KTC/FBX mixtures, respectively. Linear regression lines were obtained over the concentration ranges 0.20-0.60 and 0.60-1.95 ug band( 1)for KTC and PHE (Mixture 1), respectively, and 0.10-1.00 and 0.25-2.50 ug band( 1) for KTC and FBX (Mixture 2), respectively, with correlation coefficients higher than 0.999. The method was successfully applied to the analysis of the two drugs in their synthetic mixtures and in their dosage forms. The mean percentage recoveries were in the range of 98-102%, and the RSD did not exceed 2%. The method was validated according to ICH guidelines and showed good performances in terms of linearity, sensitivity, precision, accuracy and stability. PMID- 26847919 TI - Extraction and Separation of Vitisin D, Ampelopsin B and cis-Vitisin A from Iris lactea Pall. var. chinensis (Fisch.) Koidz by Alkaline Extraction-Acid Precipitation and High-Speed Counter-Current Chromatography. AB - Naturally occurring oligostilbenes are receiving more attention because they exhibit several beneficial effects for health, including hepatoprotective, antitumor, anti-adipogenic, antioxidant, antiaging, anti-inflammatory, anti microbial, antiviral, immunosuppressive and neuroprotective activities. Thus, they could be of some potentially therapeutic values for several diseases. In this study, we adopted the alkaline extraction-acid precipitation (AEAP) method for extraction of oligostilbenes from the seed kernel of Iris lactea Then, the high-speed counter-current chromatography (HSCCC) was used for preparative isolation and purification of oligostilbenes from the AEAP extracts. Finally, three oligostilbenes, namely vitisin D (73 mg), ampelopsin B (25 mg) and cis vitisin A (16 mg), were successfully fractionated by HSCCC with a two-phase solvent system composed of n-hexane-ethyl acetate-methanol-water (2:5:3:6, v/v/v/v) from 300 mg of the AEAP extracts in ~ 190 min. The purities of the three isolated oligostilbenes were all over 95.0% as analyzed by high performance liquid chromatography. They all were isolated from I. lacteal for the first time.The method of AEAP for the preparation of the oligostilbene-enriched crude sample was simple, and the HSCCC technique for the isolation and purification of oligostilbenes was efficient. PMID- 26847921 TI - From synchrotron radiation to lab source: advanced speckle-based X-ray imaging using abrasive paper. AB - X-ray phase and dark-field imaging techniques provide complementary and inaccessible information compared to conventional X-ray absorption or visible light imaging. However, such methods typically require sophisticated experimental apparatus or X-ray beams with specific properties. Recently, an X-ray speckle based technique has shown great potential for X-ray phase and dark-field imaging using a simple experimental arrangement. However, it still suffers from either poor resolution or the time consuming process of collecting a large number of images. To overcome these limitations, in this report we demonstrate that absorption, dark-field, phase contrast, and two orthogonal differential phase contrast images can simultaneously be generated by scanning a piece of abrasive paper in only one direction. We propose a novel theoretical approach to quantitatively extract the above five images by utilising the remarkable properties of speckles. Importantly, the technique has been extended from a synchrotron light source to utilise a lab-based microfocus X-ray source and flat panel detector. Removing the need to raster the optics in two directions significantly reduces the acquisition time and absorbed dose, which can be of vital importance for many biological samples. This new imaging method could potentially provide a breakthrough for numerous practical imaging applications in biomedical research and materials science. PMID- 26847920 TI - Co-expression of Dorsal and Rel2 Negatively Regulates Antimicrobial Peptide Expression in the Tobacco Hornworm Manduca sexta. AB - Nuclear factor kappaB (NF-kappaB) plays an essential role in regulation of innate immunity. In mammals, NF-kappaB factors can form homodimers and heterodimers to activate gene expression. In insects, three NF-kappaB factors, Dorsal, Dif and Relish, have been identified to activate antimicrobial peptide (AMP) gene expression. However, it is not clear whether Dorsal (or Dif) and Relish can form heterodimers. Here we report the identification and functional analysis of a Dorsal homologue (MsDorsal) and two Relish short isoforms (MsRel2A and MsRel2B) from the tobacco hornworm, Manduca sexta. Both MsRel2A and MsRel2B contain only a Rel homology domain (RHD) and lack the ankyrin-repeat inhibitory domain. Overexpression of the RHD domains of MsDorsal and MsRel2 in Drosophila melanogaster S2 and Spodoptera frugiperda Sf9 cells can activate AMP gene promoters from M. sexta and D. melanogaster. We for the first time confirmed the interaction between MsDorsal-RHD and MsRel2-RHD, and suggesting that Dorsal and Rel2 may form heterodimers. More importantly, co-expression of MsDorsal-RHD with MsRel2-RHD suppressed activation of several M. sexta AMP gene promoters. Our results suggest that the short MsRel2 isoforms may form heterodimers with MsDorsal as a novel mechanism to prevent over-activation of antimicrobial peptides. PMID- 26847923 TI - Expression profile of long non-coding RNAs in colorectal cancer: A microarray analysis. AB - Colorectal cancer (CRC) is one of the most prevalent malignant tumors and the second cause of cancer-related mortality worldwide. Due to increased morbidity and mortality rates, there is an urgent need to understand the pathogenesis of CRC, discover strategies that can improve diagnosis, and ultimately identify therapies targeting this disease. Over the past several years, research into tumor progression mechanisms has been devoted to identifying and understanding various coding and non-coding regions of the genome and how these genetic variants may affect tumorigenesis and progression. Recently, long non-coding RNAs (lncRNAs), which are non-protein coding transcripts longer than 200 nucleotides, have emerged as a key aspect in tumor pathogenesis. In the present study, we examined the lncRNA and mRNA expression profiles in 4 patients with colon adenocarcinoma, with paired adjacent normal tissues as controls. Microarray data showed that a total of 3,523 lncRNAs and 2,515 mRNAs were consistently differentially expressed in the CRC tissues compared to adjacent normal tissues. Upon comparison of the differentially expressed transcripts between the groups, we identified 22 pathways which were related to the upregulated transcripts and 24 pathways that corresponded to the downregulated transcripts. Gene ontology analysis revealed that the upregulated transcripts were predominantly enriched in DNA metabolic processes, and the downregulated transcripts were predominantly enriched in organic hydroxyl compound metabolic processes. Coding-non-coding gene co-expression analysis showed that these differentially expressed lncRNAs were closely correlated with 'Wnt signaling pathway' components, whose aberrant activation plays a central role in CRC, indicating that a functional correlation exists between them. In conclusion, the results of the microarray and informatic analysis strongly suggest that lncRNA dysregulation is involved in the complicated process of CRC development, and may represent a novel class of diagnostic markers or therapeutic targets for CRC. PMID- 26847922 TI - Mortality prediction in patients with severe septic shock: a pilot study using a target metabolomics approach. AB - Septic shock remains a major problem in Intensive Care Unit, with high lethality and high-risk second lines treatments. In this preliminary retrospective investigation we examined plasma metabolome and clinical features in a subset of 20 patients with severe septic shock (SOFA score >8), enrolled in the multicenter Albumin Italian Outcome Sepsis study (ALBIOS, NCT00707122). Our purpose was to evaluate the changes of circulating metabolites in relation to mortality as a pilot study to be extended in a larger cohort. Patients were analyzed according to their 28-days and 90-days mortality. Metabolites were measured using a targeted mass spectrometry-based quantitative metabolomic approach that included acylcarnitines, aminoacids, biogenic amines, glycerophospholipids, sphingolipids, and sugars. Data-mining techniques were applied to evaluate the association of metabolites with mortality. Low unsaturated long-chain phosphatidylcholines and lysophosphatidylcholines species were associated with long-term survival (90 days) together with circulating kynurenine. Moreover, a decrease of these glycerophospholipids was associated to the event at 28-days and 90-days in combination with clinical variables such as cardiovascular SOFA score (28-day mortality model) or renal replacement therapy (90-day mortality model). Early changes in the plasma levels of both lipid species and kynurenine associated with mortality have potential implications for early intervention and discovering new target therapy. PMID- 26847924 TI - Sequential Adeno-Associated Viral Vector Serotype 9-Green Fluorescent Protein Gene Transfer Causes Massive Inflammation and Intense Immune Response in Rat Striatum. AB - Green fluorescent protein (GFP) is a broadly used live cell reporter for gene transduction although side effects associated with GFP in gene transfer are reported. The present study was designed to systematically examine host responses, including inflammatory and immune responses, induced by persistent overexpression of the GFP gene mediated by adeno-associated viral vector serotype 9 (AAV9), and their effects on GFP gene transduction in rat striatum. Our results show that host responses against AAV9-GFP transduction, and GFP transgene expression in the striatum exhibited a temporal and dose-dependent pattern. Both muscular and striatal delivery of AAV9-GFP increased levels of inflammation and immune reactions against sequential AAV9-GFP transduction in the striatum, leading to reduced levels of GFP expression. We also observed that rat sera from sequential administrations of AAV9-GFP group had significantly higher levels of neutralizing antibody against AAV9 vectors when compared with the age-matched rats. As excessive GFP can trigger vigorous inflammation and intense immune response after GFP gene transduction, the use of GFP as a live cell marker protein should be deliberated, especially in repeated administration studies. PMID- 26847926 TI - NAD(P)H dehydrogenase, quinone 1 (NQO1), protects melanin-producing cells from cytotoxicity of rhododendrol. AB - Rhododendrol (RD) is a potent tyrosinase inhibitor that is metabolized to RD quinone by tyrosinase, which may underlie the cytotoxicity of RD and leukoderma of the skin that may result. We have examined how forced expression of the NAD(P)H quinone dehydrogenase, quinone 1 (NQO1), a major quinone-reducing enzyme in cytosol, affects the survival of RD-treated cells. We found that treatment of the mouse melanoma cell line B16BL6 or normal human melanocytes with carnosic acid, a transcriptional inducer of the NQO1 gene, notably suppressed the cell killing effect of RD. This effect was mostly abolished by ES936, a highly specific NQO1 inhibitor. Moreover, conditional overexpression of the human NQO1 transgene in B16BL6 led to an expression-dependent increase of cell survival after RD treatment. Our results suggest that NQO1 attenuates the cytotoxicity of RD and/or its metabolites. PMID- 26847925 TI - Structural basis for two-step glucose trimming by glucosidase II involved in ER glycoprotein quality control. AB - The endoplasmic reticulum (ER) has a sophisticated protein quality control system for the efficient folding of newly synthesized proteins. In this system, a variety of N-linked oligosaccharides displayed on proteins serve as signals recognized by series of intracellular lectins. Glucosidase II catalyzes two-step hydrolysis at alpha1,3-linked glucose-glucose and glucose-mannose residues of high-mannose-type glycans to generate a quality control protein tag that is transiently expressed on glycoproteins and recognized by ER chaperones. Here we determined the crystal structures of the catalytic alpha subunit of glucosidase II (GIIalpha) complexed with two different glucosyl ligands containing the scissile bonds of first- and second-step reactions. Our structural data revealed that the nonreducing terminal disaccharide moieties of the two kinds of substrates can be accommodated in a gourd-shaped bilocular pocket, thereby providing a structural basis for substrate-binding specificity in the two-step deglucosylation catalyzed by this enzyme. PMID- 26847927 TI - Dressed to kill? Visible markers of coalitional affiliation enhance conceptualized formidability. AB - Displaying markers of coalitional affiliation is a common feature of contemporary life. In situations in which interaction with members of rival coalitions is likely, signaling coalitional affiliation may simultaneously constitute an implicit challenge to opponents and an objective commitment device, binding signalers to their coalitions. Individuals who invite conflict, and who cannot readily back out of conflict, constitute a greater threat than those who avoid conflict and preserve the option of feigning neutrality. As a consequence, the former should be viewed as more formidable than the latter. Recent research indicates that relative formidability is summarized using the envisioned physical size and strength of a potential antagonist. Thus, individuals who display markers of coalitional affiliation should be conceptualized as more physically imposing than those who do not. We tested this prediction in two experiments. In Study 1, conducted with U.S. university students, participants inspected images of sports fans' faces. In Study 2, conducted with U.S. Mechanical Turk workers, participants read vignettes depicting political partisans. In both studies, participants estimated the physical formidability of the target individuals and reported their own ability to defend themselves; in Study 2, participants estimated the target's aggressiveness. Consonant with predictions, targets depicted as signaling coalitional affiliation in situations of potential conflict were envisioned to be more physically formidable and more aggressive than were those not depicted as signaling thusly. Underscoring that the calculations at issue concern the possibility of violent conflict, participants' estimates of the protagonist's features were inversely correlated with their ability to defend themselves. PMID- 26847928 TI - Mutations of the RTEL1 Helicase in a Hoyeraal-Hreidarsson Syndrome Patient Highlight the Importance of the ARCH Domain. AB - The DNA helicase RTEL1 participates in telomere maintenance and genome stability. Biallelic mutations in the RTEL1 gene account for the severe telomere biology disorder characteristic of the Hoyeraal-Hreidarsson syndrome (HH). Here, we report a HH patient (P4) carrying two novel compound heterozygous mutations in RTEL1: a premature stop codon (c.949A>T, p.Lys317*) and an intronic deletion leading to an exon skipping and an in-frame deletion of 25 amino-acids (p.Ile398_Lys422). P4's cells exhibit short and dysfunctional telomeres similarly to other RTEL1-deficient patients. 3D structure predictions indicated that the p.Ile398_Lys422 deletion affects a part of the helicase ARCH domain, which lines the pore formed with the core HD and the iron-sulfur cluster domains and is highly specific of sequences from the eukaryotic XPD family members. PMID- 26847929 TI - Direct preparation of high quality graphene on dielectric substrates. AB - Graphene, an amazing two-dimensional material with excellent physical properties, has attracted great attention in various disciplines. Both fundamental studies and applications require graphene samples with controlled parameters including their quality, size, crystallinity, layer number and so on. While graphene can be prepared by direct exfoliation from mother materials or growth on transition metals, the uncontrolled production or the additional complex transfer process has been challenging for graphene applications. Direct preparation on a desired dielectric substrate is an important research direction that potentially addresses these problems. Many advances have been made in the past few years, and this tutorial review provides a brief summary of ways of preparing graphene on dielectric substrates. Various methods including the annealing method, direct chemical vapor deposition graphene synthesis on conventional dielectric substrates and hexagonal boron nitride layers are systematically reviewed and discussed. The main problems and further directions in this field are also presented. PMID- 26847930 TI - Cannabinoid receptor type 1 mediates high-fat diet-induced insulin resistance by increasing forkhead box O1 activity in a mouse model of obesity. AB - Hepatic glucose production is promoted by forkhead box O1 (FoxO1) under conditions of insulin resistance. The overactivity of cannabinoid receptor type 1 (CB1R) partly causes increased liver fat deposits and metabolic dysfunction in obese rodents by decreasing mitochondrial function. The aim of the present study was to investigate the role of FoxO1 in CB1R-mediated insulin resistance through the dysregulation of mitochondrial function in the livers of mice with high-fat diet (HFD)-induced obesity. For this purpose, male C57BL/6 mice were randomly assigned to groups and either fed a standard diet (STD), a HFD, or a HFD with 1 week treatment of the CB1R inverse agonist, AM251, at 1 or 5 mg/kg. For in vitro experiments, AML12 hepatocytes were incubated with FoxO1 siRNA prior to challenge with arachidonyl-2'-chloroethylamide (ACEA) or a high concentration of free fatty acids (HFFA). Plasma parameters were analyzed using colorimetric methods. Liver histopathology and hepatic status markers were examined. The HFD-fed mice exhibited an increase in CB1R levels in the liver. Moreover, in response to increased hepatic oxidative stress, the HFD-fed mice also displayed hepatic mitochondrial dysfunction, as indicated by the decreased mRNA levels of carnitine palmitoyltransferase-1 (CPT-1), mitochondrial transcription factor A (TFAM), nuclear respiratory factor-1 (NRF-1) and citrate synthase. On the contrary, these effects in the HFD-fed mice were reversed by treatment with 5 mg/kg AM251. The administration of AM251 suppressed the induction of FoxO1, phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) expression in the livers of the mice fed a HFD by enhancing the phosphorylation of insulin signaling cascades thus, further lowering the high level of the homeostatic model assessment of insulin resistance (HOMA-IR) index. In our in vitro experiments, transfection with FoxO1 siRNA prevented the HFFA- and ACEA-induced decrease in the gene expression of mitochondrial biogenesis-related factors, and abrogated the HFFA- and ACEA-induced increase in PEPCK and G6Pase expression. Taken together, our findings suggest that the anti-insulin resistance effect of AM251, which leads to an improvement of mitochondrial function in hepatic steatosis, is mediated through FoxO1. PMID- 26847931 TI - Size, but not experience, affects the ontogeny of constriction performance in ball pythons (Python regius). AB - Constriction is a prey-immobilization technique used by many snakes and is hypothesized to have been important to the evolution and diversification of snakes. However, very few studies have examined the factors that affect constriction performance. We investigated constriction performance in ball pythons (Python regius) by evaluating how peak constriction pressure is affected by snake size, sex, and experience. In one experiment, we tested the ontogenetic scaling of constriction performance and found that snake diameter was the only significant factor determining peak constriction pressure. The number of loops applied in a coil and its interaction with snake diameter did not significantly affect constriction performance. Constriction performance in ball pythons scaled differently than in other snakes that have been studied, and medium to large ball pythons are capable of exerting significantly higher pressures than those shown to cause circulatory arrest in prey. In a second experiment, we tested the effects of experience on constriction performance in hatchling ball pythons over 10 feeding events. By allowing snakes in one test group to gain constriction experience, and manually feeding snakes under sedation in another test group, we showed that experience did not affect constriction performance. During their final (10th) feedings, all pythons constricted similarly and with sufficiently high pressures to kill prey rapidly. At the end of the 10 feeding trials, snakes that were allowed to constrict were significantly smaller than their non constricting counterparts. PMID- 26847932 TI - Macrophage migration inhibitory factor induces autophagy to resist hypoxia/serum deprivation-induced apoptosis via the AMP-activated protein kinase/mammalian target of rapamycin signaling pathway. AB - Macrophage migration inhibitory factor (MIF) is an anti-apoptotic agent in various cell types and protects the heart from stress-induced injury by modulating autophagy. Autophagy, a conserved pathway for bulk degradation of intracellular proteins and organelles, helps to preserve and recycle energy and nutrients for cells to survive during starvation. The present study hypothesized that MIF protects bone marrow-derived mesenchymal stem cells (MSCs) from apoptosis by modulating autophagy via the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. MSCs were obtained from rat bone marrow and cultured. Apoptosis was induced by hypoxia/serum deprivation for 24 h and was assessed using flow cytometry. MIF protected MSCs from apoptosis by modulating autophagy via the AMPK/mTOR signaling pathway resulting in increased expression of autophagy-associated proteins (including LC3BI/LC3BII, Beclin-1 and autophagy protein 5), and by increased phosphorylation of AMPK and decreased phosphorylation of mTOR. The MIF anti-apoptotic effects were blocked by autophagy inhibitor, 3-methyladenine or AMPK inhibitor, Compound C. These results indicate that MIF exerts a permissive role in protecting MSCs from apoptosis by regulation of autophagy via the AMPK/mTOR signaling pathway. PMID- 26847933 TI - Preparation of graphite intercalation compounds containing oligo and polyethers. AB - Layered host-polymer nanocomposites comprising polymeric guests between inorganic sheets have been prepared with many inorganic hosts, but there is limited evidence for the incorporation of polymeric guests into graphite. Here we report for the first time the preparation, and structural and compositional characterization of graphite intercalation compounds (GICs) containing polyether bilayers. The new GICs are obtained by either (1) reductive intercalation of graphite with an alkali metal in the presence of an oligo or polyether and an electrocatalyst, or (2) co-intercalate exchange of an amine for an oligo or polyether in a donor-type GIC. Structural characterization of products using powder X-ray diffraction, Raman spectroscopy, and thermal analyses supports the formation of well-ordered, first-stage GICs containing alkali metal cations and oligo or polyether bilayers between reduced graphene sheets. PMID- 26847934 TI - Efficacy of one-stage surgical treatment and clinical features in patients with multiple pressure ulcers. AB - Treating patients with multiple pressure ulcers is a very challenging task for physicians. However, there are very few reports on treatment protocols for multiple pressure ulcers and treatment outcomes. The authors have consistently treated multiple pressure ulcers in a one-stage operation rather than a staged operation. We evaluated multiple pressure ulcers patients who underwent a one stage operation from 2007 to 2014. A comparison was made between 20 patients who underwent a one-stage operation on 44 foci and 68 patients with a single focus. Though the results, we could conclude that one-stage operation of multiple pressure ulcers was found to have a shorter recovery period and shorter hospitalization without a significant increase in complications. PMID- 26847935 TI - Prospective study on Incontinence-Associated Dermatitis and its Severity instrument for verifying its ability to predict the development of pressure ulcers in patients with fecal incontinence. AB - Fecal incontinence with loose stools is a risk factor for skin damage that may develop into a pressure ulcer (PU). The aim of this study was to determine the feasibility of applying the Incontinence-Associated Dermatitis and its Severity (IADS) instrument to patients with fecal incontinence as a tool to predict PU development. This prospective study enrolled 120 intensive care unit patients with bowel incontinence of Bristol Stool type 5, 6, and 7. Trained nurses evaluated IADS scores and the occurrence of PUs daily for 7 days. Patients with higher IADS scores were significantly more likely to develop a PU (odds ratio = 1.22, 95% confidence interval = 1.12-1.33). The receiver operating characteristic curve analysis revealed the area under curve to be 0.790, suggesting that higher IADS scores are associated with an increased likelihood of developing a PU (sensitivity 72.5%, specificity 71.2%, using a cut-off value of 8/9). Our results suggest that the IADS instrument can serve as a tool for predicting the occurrence of PUs in patients with fecal incontinence. Patients with IADS scores that exceed eight points should be classified as being at risk of developing a PU, and placed under intensive care as a proactive measure to prevent PU development. PMID- 26847936 TI - Effects of pressure ulcer classification system education programme on knowledge and visual differential diagnostic ability of pressure ulcer classification and incontinence-associated dermatitis for clinical nurses in Korea. AB - The objective of this study was to evaluate the effect of pressure ulcer classification system education on clinical nurses' knowledge and visual differential diagnostic ability of pressure ulcer (PU) classification and incontinence-associated dermatitis (IAD). One group pre and post-test was used. A convenience sample of 407 nurses, participating in PU classification education programme of continuing education, were enrolled. The education programme was composed of a 50-minute lecture on PU classification and case-studies. The PU Classification system and IAD knowledge test (PUCS-KT) and visual differential diagnostic ability tool (VDDAT), consisting of 21 photographs including clinical information were used. Paired t-test was performed using SPSS/WIN 20.0. The overall mean difference of PUCS-KT (t = -11.437, P<0.001) and VDDAT (t = -21.113, P<0.001) was significantly increased after PU classification education. Overall understanding of six PU classification and IAD after education programme was increased, but lacked visual differential diagnostic ability regarding Stage III PU, suspected deep tissue injury (SDTI), and Unstageable. Continuous differentiated education based on clinical practice is needed to improve knowledge and visual differential diagnostic ability for PU classification, and comparison experiment study is required to examine effects of education programmes. PMID- 26847937 TI - The effect of diabetes on the wound healing potential of adipose-tissue derived stem cells. AB - To investigate whether diabetes mellitus affects the wound-healing-promoting potential of adipose tissue-derived stem cells, we designed a wound-healing model using diabetic mice. We compared the degree of wound healing between wounds treated with normal adipose tissue-derived stem cells and wounds treated with diabetic adipose tissue-derived stem cells. We evaluated the wound-healing rate, the epithelial tongue distance, the area of granulation tissue, the number of capillary and the number of Ki-67-stained cells. The wound-healing rate was significantly higher in the normal adipose tissue-derived stem cells group than in the diabetic adipose tissue-derived stem cells group; it was also significantly higher in the normal adipose tissue-derived stem cells group than in the control group. Although the diabetic adipose tissue-derived stem cells group showed a better wound-healing rate than the control group, the difference was not statistically significant. Similar trends were observed for the other parameters examined: re-epithelisation and keratinocyte proliferation; granulation tissue formation; and dermal regeneration. However, with regard to the number of capillary, diabetic adipose tissue-derived stem cells retained their ability to promote neovasculisation and angiogenesis. These results reflect the general impairment of the therapeutic potential of diabetic adipose tissue derived stem cells in vivo. PMID- 26847938 TI - A descriptive study of Korean nurses' perception of pain and skin tearing at dressing change. AB - This study aimed to investigate Korean nurses' level of awareness of pain and skin tearing in wound bed and/or peri-wound skin at dressing change. A descriptive study was performed. Convenience sampling was employed and registered nurses were recruited from attendees of continuing education program. A total of 399 participants (RN) completed questionnaire. Data was collected from September to November 2014. Many of them perceived skin tearing and wound related pain associated with dressing changing, but most of them did not assess and record pain and skin tearing at dressing change. More than half of respondents reported that they did not provide nursing intervention to prevent pain and skin tearing. Many of them reported that a systematic educational program for preventing pain and skin tearing at dressing change was needed. In conclusion, many of respondents were aware of pain and skin tearing at dressing change, but did not take any further necessary measures, including nursing intervention, for the most appropriate, systematic pain and skin tearing management. Therefore, this study suggested that a systematic and comprehensive educational program for Korean healthcare professions needs to be developed and implemented in Korea's hospital settings. PMID- 26847944 TI - The 2016 Hughes Lecture: What's new in maternal morbidity and mortality? AB - Each year, the Board of Directors of the Society for Obstetric Anesthesia and Perinatology selects an individual to review a given year's published obstetric anesthesiology literature. This individual then produces a syllabus of the year's most influential publications, delivers the Ostheimer Lecture at the Society's annual meeting, the Hughes Lecture at the following year's Sol Shnider meeting, and writes corresponding review articles. This 2016 Hughes Lecture review article focuses specifically on the 2014 publications that relate to maternal morbidity and mortality. It begins by discussing the 2014 research that was published on severe maternal morbidity and maternal mortality in developed countries. This is followed by a discussion of specific coexisting diseases and specific causes of severe maternal mortality. The review ends with a discussion of worldwide maternal mortality and the 2014 publications that examined the successes and the shortfalls in the work to make childbirth safe for women throughout the entire world. PMID- 26847945 TI - Psychopathology, psychopharmacological properties, decision-making capacity to consent to clinical research and the willingness to participate among long-term hospitalized patients with schizophrenia. AB - Many studies discuss factors related to the decision-making capacity to consent to clinical research (DMC) of patients with schizophrenia. However, these studies rarely approached willingness to participate and the association between psychopharmacological properties (e.g., antipsychotic-induced side effects) and DMC. This study aimed to explore factors related to DMC and willingness to participate in patients with schizophrenia. All 139 patients with schizophrenia were assessed with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and other measures. A linear regression model was used to find the predictors of MacCAT-CR scores. A logistic regression model was used for exploring the predictors of willingness to participate. Patients with more severe negative symptoms performed poorly in DMC outcomes. In addition, females, those with fewer years of education and reduced cognitive function are more likely to experience difficulties in decision-making. Forty-three subjects (30.4%) chose to participate. Patients with higher level of positive symptoms, longer length of stay, higher burden of anticholinergics and users of atypical antipsychotics were more likely to participate in a clinical study which aimed to "enhance cognition". These finding suggest that research investigators should consider many variables for patients who require more intensive screening for impaired DMC. PMID- 26847946 TI - Self-inflicted pain out of boredom. AB - Previous research has shown that in response to a monotonous, boring lab situation, non-clinical participants voluntarily self-administer electric shocks. The shocks probably served to disrupt the tedious monotony: they were the only available external source of stimulation. Alternatively, the shocks might have functioned to regulate the negative emotional experience caused by the induction of boredom, consistent with theories on the function of non-suicidal self-injury (NSSI). According to this latter explanation, induction of other negative emotions would also increase the administration of shocks. To test this explanation, 69 participants watched a monotonous, sad or neutral film fragment, during which they could self-administer electric shocks. Participants in the boredom condition self-administered more shocks and with higher intensity, compared to both the neutral and sadness condition. Sadness had no effect on the self-administration of shocks. The effect of boredom was more pronounced in participants with a history of NSSI: they administered more shocks in the first 15min. The results indicate that the shocks function to disrupt monotony and not to regulate negative emotional experience in general. Moreover, boredom appears an important impetus for NSSI. PMID- 26847947 TI - Oral nutritional supplements in a randomised trial are more effective than dietary advice at improving quality of life in malnourished care home residents. AB - BACKGROUND & AIMS: Few trials have explored the effect of nutrition support on quality of life (QoL). This study examined the effects of oral nutritional supplements (ONS) vs dietary advice on QoL in malnourished care home residents. METHODS: 104 malnourished, care home residents (medium + high risk), identified using the Malnutrition Universal Screening Tool ('MUST'), (mean age 88.5 +/- 7.9y) were randomised to receive either oral nutritional supplements (ONS) (n = 53) or dietary advice (n = 51) for 12 weeks. Dietary intake was measured using 24 h dietary recall, and QoL assessed using EuroQol (EQ-5D), including time trade off (TTO) (range -0.59 to 1) and visual analogue scale (VAS) (score 0 to 100) for self-perceived health. RESULTS: QoL (adjusted for baseline QOL, malnutrition risk, type of care received (nursing or residential)) was significantly higher in the ONS than the dietary advice group (intention to treat analysis at week 12; n = 104 ). EQ-5D TTO scores (mean +/- SE) were 0.50 +/- 0.04 vs 0.36 +/- 0.05 (P = 0.005), VAS rescaled scores were 0.54 + 0.03 vs 0.046 + 0.03 (P = 0.006) and VAS scores were 61.3 +/- 4.5 vs 54.6 +/- 6.3 (P = 0.533) for ONS vs dietary advice respectively. Total energy, protein and the majority of micronutrient intakes were significantly greater in the ONS group, with energy intake being 423 kcal greater in the ONS than the dietary advice group at week 12. CONCLUSIONS: This study in malnourished care home residents indicates that ONS can improve QoL and nutritional intake more effectively than dietary advice alone. CLINICAL TRIAL REGISTRY: This trial was registered with clinicaltrials.gov on 10th August 2007. Clinical trials identifier is NCT00515125http://www.clinicaltrials.gov/ct2/show/NCT00515125?term=nutrition+supp rt&rank=60. PMID- 26847948 TI - Primary hypolactasia diagnosis: Comparison between the gaxilose test, shortened lactose tolerance test, and clinical parameters corresponding to the C/T-13910 polymorphism. AB - BACKGROUND & AIMS: There is no consensus on the most accurate method to diagnose primary hypolactasia. We aimed to compare the diagnostic accuracy of the new gaxilose test with 2 traditional tests (lactose tolerance test and clinical criteria) for the diagnosis of primary hypolactasia using the C/T-13910 polymorphism as a reference standard. METHODS: Patients with a clinical suspicion of lactose intolerance were subjected to gaxilose tests, shortened lactose tolerance tests, and symptom questionnaires before and after overload with 50 g lactose and after a lactose-free diet. The diagnostic accuracy and degree of agreement and correlation were assessed using a genetic test (C/T-13910 polymorphism) as a reference standard and their respective 95% confidence intervals. RESULTS: Thirty consecutive patients (70% women) participated in the study. The genetic test confirmed the C/T-13910 polymorphism in 11 patients (36.8%). The presence of diarrhoea and the symptom score after lactose overload, along with the tolerance test, were the variables with the highest degree of agreement (kappa > 0.60). Area under the ROC curve was >0.82 (p < 0.05), with sensitivity and specificity values of >0.80. However, the gaxilose test obtained lower values: kappa, 0.47; area under curve, 0.75 (0.57-0.94); sensitivity, 0.82 (0.55-1); and specificity, 0.68 (0.45-0.92). The multivariate analysis showed an association between the post-overload symptom questionnaire and the results of the genetic test (odds ratio: 1.17; 1.04-1.31; p < 0.01). CONCLUSIONS: The presence of diarrhoea and the symptom score after overload with 50 g lactose showed a higher degree of agreement and diagnostic accuracy for primary hypolactasia than the gaxilose test when the genetic test is used as a reference standard. PMID- 26847949 TI - Crash risk analysis for Shanghai urban expressways: A Bayesian semi-parametric modeling approach. AB - Urban expressway systems have been developed rapidly in recent years in China; it has become one key part of the city roadway networks as carrying large traffic volume and providing high traveling speed. Along with the increase of traffic volume, traffic safety has become a major issue for Chinese urban expressways due to the frequent crash occurrence and the non-recurrent congestions caused by them. For the purpose of unveiling crash occurrence mechanisms and further developing Active Traffic Management (ATM) control strategies to improve traffic safety, this study developed disaggregate crash risk analysis models with loop detector traffic data and historical crash data. Bayesian random effects logistic regression models were utilized as it can account for the unobserved heterogeneity among crashes. However, previous crash risk analysis studies formulated random effects distributions in a parametric approach, which assigned them to follow normal distributions. Due to the limited information known about random effects distributions, subjective parametric setting may be incorrect. In order to construct more flexible and robust random effects to capture the unobserved heterogeneity, Bayesian semi-parametric inference technique was introduced to crash risk analysis in this study. Models with both inference techniques were developed for total crashes; semi-parametric models were proved to provide substantial better model goodness-of-fit, while the two models shared consistent coefficient estimations. Later on, Bayesian semi-parametric random effects logistic regression models were developed for weekday peak hour crashes, weekday non-peak hour crashes, and weekend non-peak hour crashes to investigate different crash occurrence scenarios. Significant factors that affect crash risk have been revealed and crash mechanisms have been concluded. PMID- 26847950 TI - [Prevalence of Chronic Obstructive Pulmonary Disease in a Rural Area of Guadalajara, Spain]. AB - OBJECTIVE: The aim of this study was to establish the prevalence of Chronic obstructive pulmonary disease [COPD] in a rural health area and its stratification according different risk factors. METHODS: A cross-sectional, observational study was performed in Yunquera de Henares (Guadalajara, Spain) in the year 2014. A questionnaire on sociodemographic factors, tobacco consumption, age, education level and occupation was used in a randomized, stratified sample in different stages. The sample was proportional in age, sex and population centers. A total of 749 persons were included. Data were analyzed using descriptive, analytical, and multivariant statistical procedures and logistical regression. RESULTS: The prevalence of COPD was 15.8% (CI95%: 13.2-18.4) and was statistically significantly higher in elderly (64.6+/-11 years vs 58.9+/-11,7 years); males (83.2%;CI95%:85.9-80.5),smokers (40.3%;CI95%:43.8-36.8) and people with primary education (66.4%;CI95%:69.7-63). People with COPD had higher BMI (28.2%;IC95%:29.5-26.9). People working in the field was 28.6% (IC95%:20,5 36,7%). CONCLUSIONS: A high prevalence of Chronic Obstructive Pulmonary Disease was found. Occupational exposure may be an important factor in rural areas. PMID- 26847951 TI - Identification of (2S,3S)-beta-Methyltryptophan as the Real Biosynthetic Intermediate of Antitumor Agent Streptonigrin. AB - Streptonigrin is a potent antitumor antibiotic, active against a wide range of mammalian tumor cells. It was reported that its biosynthesis relies on (2S,3R) beta-methyltryptophan as an intermediate. In this study, the biosynthesis of (2S,3R)-beta-methyltryptophan and its isomer (2S,3S)-beta-methyltryptophan by enzymes from the streptonigrin biosynthetic pathway is demonstrated. StnR is a pyridoxal 5'-phosphate (PLP)-dependent aminotransferase that catalyzes a transamination between L-tryptophan and beta-methyl indolepyruvate. StnQ1 is an S adenosylmethionine (SAM)-dependent C-methyltransferase and catalyzes beta methylation of indolepyruvate to generate (R)-beta-methyl indolepyruvate. Although StnR exhibited a significant preference for (S)-beta-methyl indolepyruvate over the (R)-epimer, StnQ1 and StnR together catalyze (2S,3R)-beta methyltryptophan formation from L-tryptophan. StnK3 is a cupin superfamily protein responsible for conversion of (R)-beta-methyl indolepyruvate to its (S) epimer and enables (2S,3S)-beta-methyltryptophan biosynthesis from L-tryptophan when combined with StnQ1 and StnR. Most importantly, (2S,3S)-beta methyltryptophan was established as the biosynthetic intermediate of the streptonigrin pathway by feeding experiments with a knockout mutant, contradicting the previous proposal that stated (2S,3R)-beta-methyltryptophan as the intermediate. These data set the stage for the complete elucidation of the streptonigrin biosynthetic pathway, which would unlock the potential of creating new streptonigrin analogues by genetic manipulation of the biosynthetic machinery. PMID- 26847952 TI - Effects of mouse slant and desktop position on muscular and postural stresses, subject preference and performance in women aged 18-40 years. AB - This study compared muscular and postural stresses, performance and subject preference in women aged 18-40 years using a standard mouse, a vertical mouse and a slanted mouse in three different computer workstation positions. Four tasks were analysed: pointing, pointing-clicking, pointing-clicking-dragging and grasping-pointing the mouse after typing. Flexor digitorum superficialis (FDS) and extensor carpi radialis (ECR) activities were greater using the standard mouse compared to the vertical or slanted mouse. In all cases, the wrist position remained in the comfort zone recommended by standard ISO 11228-3. The vertical mouse was less comfortable and more difficult to use than the other two mice. FDS and ECR activities, shoulder abduction and wrist extension were greater when the mouse was placed next to the keyboard. Performance and subject preference were better with the unrestricted mouse positioning on the desktop. Grasping the mouse after typing was the task that caused the greatest stress. Practitioner Summary: In women, the slanted mouse and the unrestricted mouse positioning on the desktop provide a good blend of stresses, performance and preference. Unrestricted mouse positioning requires no keyboard, which is rare in practice. Placing the mouse in front of the keyboard, rather than next to it, reduced the physical load. PMID- 26847954 TI - BCR-ABL1-positive and JAK2 V617F-positive clones in 23 patients with both aberrations reveal biologic and clinical importance. PMID- 26847953 TI - Developmental trajectories of cerebrovascular reactivity in healthy children and young adults assessed with magnetic resonance imaging. AB - KEY POINTS: Cerebrovascular reactivity (CVR) reflects the vasodilatory reserve of cerebral resistance vessels. Normal development in children is associated with significant changes in blood pressure, cerebral blood flow (CBF) and cerebral oxygen metabolism. Therefore, it stands to reason that CVR will also undergo changes during this period. The study acquired magnetic resonance imaging measures of CVR and CBF in healthy children and young adults to trace their changes with age. We found that CVR changes in two phases, increasing with age until the mid-teens, followed by a decrease. Baseline CBF declined steadily with age. We conclude that CVR varies with age during childhood, which prompts future CVR studies involving children to take into account the effect of development. ABSTRACT: Cerebrovascular reactivity (CVR) reflects the vasculature's ability to accommodate changes in blood flow demand thereby serving as a critical imaging tool for mapping vascular reserve. Normal development is associated with extensive physiological changes in blood pressure, cerebral blood flow and cerebral metabolic rate of oxygen, all of which can affect CVR. Moreover, the evolution of these physiological parameters is most prominent during childhood. Therefore, the aim of this study was to use non-invasive magnetic resonance imaging (MRI) to characterize the developmental trajectories of CVR in healthy children and young adults, and relate them to changes in cerebral blood flow (CBF). Thirty-four healthy subjects (17 males, 17 females; age 9-30 years) underwent CVR assessment using blood oxygen level-dependent MRI in combination with a computer controlled CO2 stimulus. In addition, baseline CBF was measured with a pulsed arterial spin labelling sequence. CVR exhibited a gradual increase with age in both grey and white matter up to 14.7 years. After this break point, a negative correlation with age was detected. Baseline CBF maintained a consistent negative linear correlation across the entire age range. The significant age-dependent changes in CVR and CBF demonstrate the evolution of cerebral haemodynamics in children and should be taken into consideration. The shift in developmental trajectory of CVR from increasing to decreasing suggests that physiological factors beyond baseline CBF also influence CVR. PMID- 26847955 TI - Insights into epidemiology of human parvovirus B19 and detection of an unusual genotype 2 variant, Bulgaria, 2004 to 2013. AB - The present study aimed to determine the role of human parvovirus V19 (B19V) as an aetiological agent in measles and rubella negative fever/rash patients from Bulgaria between 2004 and 2013. A total of 1,266 sera from all over the country were tested for B19V IgM antibodies and all positives were further investigated by polymerase chain reaction (PCR). Overall, 280 sera (22%) were B19V IgM positive and 227 of these (81%) were also PCR positive. The highest number of IgM positives was found among five to nine year-old children (27%). Eight infected women gave birth to healthy children; one fetus was aborted with hydrops fetalis. Of the 55 genetic sequences obtained, 54 belonged to genotype 1a and one grouped as a genotype 2 outlier. Phylogenetic analysis of all available genotype 2 sequences covering the 994 nucleotide non-structural protein 1(NS1)/capsid viral protein 1 (VP1) unique region junction, showed that only one other sequence grouped with the outlier strain, forming a clearly distinct and well-supported cluster of genotype 2 (between-group genetic distance: 3.32%). In accordance with B19V nomenclature, this cluster may represent a new subgenotype 2b. The study showed that B19V infections may be falsely identified as rubella or measles in ca 22% of cases, emphasising the need for laboratory confirmation. PMID- 26847956 TI - Knowledge of Vaccination Needs of HIV-Infected Men Who Have Sex with Men in a National Sample of "Gay Friendly" Health care Providers. AB - OBJECTIVES: The purpose of this study was to assess knowledge levels regarding vaccination needs of healthy, HIV-infected (with CD4 counts >200 cells/mm(3) ) men who have sex with men (MSM) in a national sample of "gay friendly" health providers. DESIGN AND SAMPLE: Participants (n = 92) were sent a demographic questionnaire and case vignette asking for correct identification of vaccine needs of an HIV-infected MSM with a CD4 count >200 cells/mm(3) . Participants were recruited from the Gay and Lesbian Medical Association's Health Provider Index. MEASURES: Descriptive statistics and Fisher's exact test were used to answer the research questions and define the sample. RESULTS: The vast majority of the sample (n = 83; 90%) misidentified correct vaccine needs of and/or selected inappropriate vaccines for the HIV-infected MSM. Greater familiarity with the CDC Adult Vaccination Schedule (p = .027), practice specialization (p = .004), and administration of vaccinations within location of practice (p = .009) were associated with greater knowledge of the patient's vaccine needs. CONCLUSIONS: Health care providers who prescribe vaccines to HIV-infected MSM need more education regarding their vaccine needs. Nurses can reduce disparities in HIV-infected MSM by advocating for vaccination and augmenting providers' comprehension of vaccine needs of this population. PMID- 26847957 TI - Dynamin-Actin Cross Talk Contributes to Phagosome Formation and Closure. AB - Phagocytosis is a mechanism used by macrophages to internalize and eliminate microorganisms or cellular debris. It relies on profound rearrangements of the actin cytoskeleton that is the driving force allowing plasma membrane extension around the particle. The closure step of phagocytosis, however, remains poorly defined. We used a dedicated experimental setup with Total Internal Reflection Fluorescence Microscopy (TIRFM) to monitor phagosome formation and closure in three dimensions in living cells. We show that dynamin-2, which mediates the scission of endocytic vesicles, was recruited early and concomitantly with actin during phagosome formation. Dynamin-2 accumulated at the site of phagosome closure in living macrophages. Inhibition of its activity with dominant negative mutants or drugs demonstrated that dynamin-2 is implicated in actin dynamics and pseudopod extension. Depolymerization of actin led to impaired dynamin-2 recruitment or activity. Finally, we show that dynamin-2 plays a critical role in the effective scission of the phagosome from the plasma membrane. Thus, we establish that a cross talk between actin and dynamin takes place for phagosome formation and closure before dynamin functions for scission. PMID- 26847958 TI - Influence of implant properties and local delivery systems on the outcome in operative fracture care. AB - Fracture fixation devices are implanted into a growing number of patients each year. This may be attributed to an increase in the popularity of operative fracture care and the development of ever more sophisticated implants, which may be used in even the most difficult clinical cases. Furthermore, as the general population ages, fragility fractures become more frequent. With the increase in number of surgical interventions, the absolute number of complications of these surgical treatments will inevitably rise. Implant-related infection and compromised fracture healing remain the most challenging and prevalent complications in operative fracture care. Any strategy that can help to reduce these complications will not only lead to a faster and more complete resumption of activities, but will also help to reduce the socio-economic impact. In this review we describe the influence of implant design and material choice on complication rates in trauma patients. Furthermore, we discuss the importance of local delivery systems, such as implant coatings and bone cement, and how these systems may have an impact on the prevalence, prevention and treatment outcome of these complications. PMID- 26847959 TI - Simpson-Golabi-Behmel syndrome: a prenatal diagnosis in a foetus with GPC3 and GPC4 gene microduplications. PMID- 26847960 TI - Shared Decision Making in Vascular Surgery: An Exploratory Study. AB - OBJECTIVES: Shared decision making (SDM) is a process in which patients and their doctors collaborate in choosing a suitable treatment option by incorporating patient values and preferences, as well as the best available evidence. Particularly in vascular surgery, several conditions seem suitable for SDM because there are multiple treatment options. The objective of this study was to assess the degree of SDM behaviour in vascular surgery. METHODS: Vascular surgeons of four Dutch hospitals selected consultations with patients who were facing a treatment decision. Immediately after the consultation, patients and surgeons completed the (subjective) SDM Q-9 and SDM Q-doc questionnaires respectively, to appreciate the perceived level of SDM behaviour. Two evaluators independently and objectively rated SDM behaviour in the audiotaped consultations, using the Observing Patient Involvement (OPTION-12) scale. RESULTS: Nine vascular surgeons and three vascular surgeons in training conducted 54 consultations. The patients' median SDM Q-9 score was high, 93% (IQR 79-100%), and 16/54 (29.6%) of them gave the maximum score. The surgeons' median score was also high, 84% (IQR 73-92%), while 4/54 (7.4%) gave the maximum score. In contrast, mean OPTION score was 31% (SD 11%). Surgeons hardly ever asked the patients for their preferred approach to receive information, whether they had understood the provided information, and how they would like to be involved in SDM. CONCLUSIONS: Currently, objective SDM behaviour among vascular surgeons is limited, even though the presented disorders allow for SDM. Hence, SDM in vascular surgical consultations could be improved by increasing the patients' and surgeons' awareness and knowledge about the concept of SDM. PMID- 26847961 TI - Corrigendum: An apoptosis-enhancing drug overcomes platinum resistance in a tumour-initiating subpopulation of ovarian cancer. PMID- 26847962 TI - Hemosuccus pancreaticus due to a tumor hemorrhage treated with a self-expandable metallic stent in a patient with unresectable pancreatic carcinoma. PMID- 26847963 TI - Systematic characterization of gastrointestinal clinical trials. AB - BACKGROUND: Clinical guidelines are commonly based on inadequate evidence, suggesting deficiencies in the present portfolio of clinical research. AIMS: To investigate characteristics of clinical trials examining gastrointestinal (GI) diseases registered in ClinicalTrials.gov. METHODS: A cross-sectional analysis of 13,647 GI trials and 111,535 non-GI trials initiated between January 1997 and September 2013 was performed. Entries were sorted by operational status, purpose, interventions, trial design, and epochs to identify trends and interactions in trial properties. RESULTS: The global production of GI trials has remained static in recent years and a majority of research efforts are focused on a few diseases. While GI trials are generally produced by highly populated US states and countries, they are also seldom larger than 500 patients. The likelihood of using data monitoring committees, randomization, and double blinding in GI trials has increased over time, though a substantial fraction of GI trials still do not employ rigorous trial designs. While levels of GI trials correlate with disease burden, the explained variance of GI trials by disease burden worldwide is poor. CONCLUSION: GI trials are chiefly concentrated in few diseases and highly populated regions, exhibit heterogeneous trends and methodologies, and are sensitive to disease burdens, though more so within North America than worldwide. PMID- 26847965 TI - [Venous angiomas and headache in children. A case report]. AB - INTRODUCTION: Venous angiomas (VA) are benign entities; however infrequent symptomatic cases may occur. OBJECTIVE: Case report and literature review. CASE REPORT: A 6 year old girl was referred with a history of bi-frontal, non pulsatile, headache with no nausea or vomiting. Headache intensity was 4-6/10. The episodes were frequent, 3-4 times per week. Triggers include academic work. Computed tomography showed a small VA in left caudate nucleus, which was confirmed by a brain MRI, with no evidence of inflammatory or ischaemic changes, or another vascular malformation. Psychological and psycho-pedagogic techniques were used, combined with relaxation and cognitive-behavioural techniques to reduce the intensity and frequency. There was a good outcome, and the headache decreased to 10 episodes per year. The patient was monitored for 12 years until graduation from high school. The VA remained without complications. CONCLUSIONS: In the study of a headache, a VA usually is an incidental finding. The International Classification of Headache Disorders III provides specific criteria of frequent episodic tension-type headache, and allows us begin specific therapy for it. Monitoring of non-symptomatic VA cases should be clinical. The surgical management of these entities is exceptional. PMID- 26847964 TI - Levofloxacin, bismuth, amoxicillin and esomeprazole as second-line Helicobacter pylori therapy after failure of non-bismuth quadruple therapy. AB - BACKGROUND: The best rescue therapy for Helicobacter pylori (H. pylori) infection following failure of non-bismuth quadruple therapy (NBQT) remains unanswered. AIMS: To determine the efficacy, safety and compliance of levofloxacin, bismuth, amoxicillin and esomeprazole (LBAE) regimen following failure of NBQT. METHODS: 132 patients with H. pylori infection refractory to first-line NBQT received LBAE regimen (levofloxacin 500mg once/day, bismuth potassium citrate 220mg twice/day, amoxicillin 1000mg twice/day and esomeprazole 20mg twice/day for 14 days). Gastric mucosal biopsy was obtained for H. pylori culture, antimicrobial sensitivity test and cytochrome P450 isoenzyme 2C19 polymorphism analysis. RESULTS: LBAE therapy achieved eradication rates of 73.5% [95% confidence intervals (CI) 65.9-81.1%] in intention-to-treat and 78.5% (71.1-85.9%) in per protocol analyses in patients with high antibiotic resistance (amoxicillin 8.3%, clarithromycin 55.6%, metronidazole 73.6% and levofloxacin 36.1%). Adverse effects were found in 19.2% and compliance in 96.1% of the treated patients. Multivariate analyses identified levofloxacin resistance [odds ratio (OR) 7.183, 95% CI 1.616-31.914, P=0.010] and history of quinolone intake (4.844, 1.174 19.983, P=0.029) as independent predictors of treatment failure. The eradication rate of patients with dual amoxicillin and levofloxacin resistance was significantly decreased (33.3%, P=0.006). CONCLUSIONS: In populations with high levofloxacin resistance, 14-day second-line LBAE regimen resulted in an unsatisfactory efficacy in patients resistant to NBQT despite good safety and compliance. PMID- 26847966 TI - Long-term adherence to continuous positive airway pressure therapy in non-sleepy sleep apnea patients. AB - OBJECTIVE: The effectiveness of continuous positive airway pressure (CPAP) therapy greatly depends on consistent use. However, data regarding adherence in non-sleepy obstructive sleep apnea (OSA) patients are scarce. The aim of this study was to assess long-term adherence and predictors of CPAP compliance in a large sample of non-sleepy OSA patients. METHODS: We conducted a prospective, multicenter study comprising 357 non-sleepy patients (Epworth Sleepiness Scale score <11) with moderate-to-severe OSA (apnea-hypopnea index [AHI] of >=20) who began CPAP therapy between May 2004 and May 2006; follow-up ended in May 2009. Non-compliance was scored as CPAP dropout or average cumulative CPAP use of <4 hours per night. Multivariate Cox regression analysis was performed to identify independent predictors of poor CPAP adherence. RESULTS: Patients were followed up for a median of four years (interquartile range [IQR] = 3.0-4.4). At the end of the study period, 230 patients (64.4%) fulfilled the criteria for good CPAP compliance, whereas 127 patients (35.6%) were considered non-compliant. The median CPAP use was five hours per night (interquartile range = 2.18-6.25). Multivariate analysis showed that interactions between the AHI and the percentage of nighttime spent with an O2 saturation of <90% (TC90) (p = 0.010) and between the AHI and hypertension at baseline (p = 0.029) predicted long-term compliance with CPAP. CONCLUSION: This study demonstrates that CPAP treatment is feasible in non-sleepy, moderate-to-severe OSA patients. Good CPAP adherence was predicted by greater OSA severity as measured by both the AHI and TC90 and by the presence of hypertension at baseline in patients with higher AHI levels. PMID- 26847967 TI - Insomnia and daytime neuropsychological test performance in older adults. AB - OBJECTIVES/BACKGROUND: There is good documentation of the impact of insomnia on daytime cognitive function based on self-reports, but not on neuropsychological test performance. The study investigated the association of difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA) complaints with daytime domain-specific neuropsychological performance in older adults. PARTICIPANTS/METHODS: Participants were 859 older adults (mean 71.9 years) in the Singapore Longitudinal Ageing Studies. They were interviewed and assessed at community-based eldercare activity centres and completed a sleep survey questionnaire and a battery of neuropsychological tests (Digit span, Rey Auditory Verbal Learning Test, Story memory, Brief Visuospatial Memory Test Revised, Color Trails Test (1 and 2), Block design, and Verbal fluency). RESULTS: Insomnia complaints were present in 18.0% (n = 155) of participants. Controlling for the presence of other insomnia complaints, psychosocial and medical variables, and depression, EMA was independently and significantly associated with worse executive functioning (p = 0.031). DIS and DMS were not independently associated with poorer performance on any cognitive domain. CONCLUSION: The association of EMA among older adults with decreased executive functioning and underlying mechanistic factors should be further investigated. PMID- 26847968 TI - The history of primary snoring in children: the effect of adenotonsillectomy. AB - Primary snoring (PS) is considered as the most benign form of sleep-disordered breathing (SDB), and treatment is usually not prescribed. Studies suggest that PS may not be as benign as had formerly been considered. We aimed to investigate the natural history of PS in children with adenotonsillar hypertrophy, and compare those who underwent adenotonsillectomy (AT) with those who did not. MATERIAL AND METHODS: Children diagnosed with PS based on polysomnographic findings were included in the study. Information retrieved from their medical records, including medical history, physical examination, anthropometric measures, and polysomnography (PSG) results, was reviewed. A telephone interview was conducted 4-6 years following the PSG evaluation. The interview included the Pediatric Sleep Questionnaire Sleep-related Breathing Disorder (PSQ-SRBD) scale, demographics, anthropometric measures, and history of AT. RESULTS: A total of 248 children (56% males) were studied (mean age: 5.4 +/- 3.4 years). Telephone interviews were conducted 5.3 +/- 1.1 years following PSG. Sixty-four children (26%) underwent AT/adenoidectomy (A) following PSG. Of the 184 children who did not undergo surgery, 62 (34%) had positive PSQ-SRBD scores five years after diagnosis. Children with PS who underwent AT had better PSQ-SRBD scores at five years post diagnosis than the nonoperated children. CONCLUSIONS: A significant proportion of children with PS persist with SDB symptoms even five years following the diagnosis. In our cohort, a considerable percentage of children with a PSG diagnosis of PS underwent AT despite non-supportive sleep study results. Surgical intervention may have beneficial effects on some children with PS. Further studies using objective measures of sleep and incorporating the effect of SDB duration are required. PMID- 26847969 TI - Relationship between obstructive sleep apnea cardiac complications and sleepiness in children with Down syndrome. AB - OBJECTIVE/BACKGROUND: Children with Down syndrome (DS) have a high rate of pulmonary hypertension and sleepiness. They also have a high prevalence of obstructive sleep apnea syndrome (OSAS). We hypothesized that OSAS was associated with cardiovascular dysfunction and sleepiness in children with DS, and that this dysfunction was partly reversible. PATIENTS/METHODS: A total of 23 children with DS, aged 8-19 years, were evaluated with polysomnography, echocardiography, and measurement of brain natriuretic peptide (BNP). Children having OSAS were randomized to four months of actual or sham continuous positive airway pressure (CPAP) in a double-blinded fashion. RESULTS: Of the total participants, 20 (87%) had OSAS. On echocardiography, no participant was found to have pulmonary hypertension, and all participants had a BNP <10 pg/mL. The early/tissue Doppler (E/e') of the lateral mitral annulus, a measure of worse left ventricular (LV) diastolic function, correlated with the arousal index (r = 0.42, p = 0.043) and apnea hypopnea index (AHI; r = 0.61, p = 0.002) and inversely with the SpO2 nadir (r = -0.61, p = 0.002). Participants with OSAS had a high pediatric Epworth score [median interquartile range (IQR) = 8(4,9)],correlating with the arousal index (r = 0.49, p = 0.016). At four months, there were no changes in cardiovascular outcomes or sleepiness between those on actual versus sham CPAP. Hours of actual CPAP use was associated with improved E/e' mitral lateral (r = -0.48, p = 0.044), but surprisingly also correlated with LV mass z-score (r = 0.54, p = 0.018). CONCLUSIONS: In children with DS, LV diastolic function correlated with OSAS severity, with improvement with CPAP use. There was a tendency towards increased sleepiness in those with OSAS, which correlated with the arousal index. Larger studies are warranted to confirm these findings. PMID- 26847970 TI - Treatment of sleep apnea in chronic heart failure patients with auto-servo ventilation improves sleep fragmentation: a randomized controlled trial. AB - BACKGROUND: Impaired sleep efficiency is independently associated with worse prognosis in patients with chronic heart failure (CHF). Therefore, a test was conducted on whether auto-servo ventilation (ASV, biphasic positive airway pressure [BiPAP]-ASV, Philips Respironics) reduces sleep fragmentation and improves sleep efficiency in CHF patients with central sleep apnea (CSA) or obstructive sleep apnea (OSA). METHODS: In this multicenter, randomized, parallel group trial, a study was conducted on 63 CHF patients (age 64 +/- 10 years; left ventricular ejection fraction 29 +/- 7%) with CSA or OSA (apnea-hypopnea Index, AHI 47 +/- 18/h; 46% CSA) referred to sleep laboratories of the four participating centers. Participants were randomized to either ASV (n = 32) or optimal medical treatment alone (control, n = 31). RESULTS: Polysomnography (PSG) and actigraphy at home (home) with centralized blinded scoring were obtained at baseline and 12 weeks. ASV significantly reduced sleep fragmentation (total arousal indexPSG: -16.4 +/- 20.6 vs. -0.6 +/- 13.2/h, p = 0.001; sleep fragmentation indexhome: -7.6 +/- 15.6 versus 4.3 +/- 13.9/h, p = 0.003, respectively) and significantly increased sleep efficiency assessed by actigraphy (SEhome) compared to controls (2.3 +/- 10.1 vs. -2.1 +/- 6.9%, p = 0.002). Effects of ASV on sleep fragmentation and efficiency were similar in patients suffering from OSA and CSA. CONCLUSIONS: At home, ASV treatment modestly improves sleep fragmentation as well as sleep efficiency in CHF patients having either CSA or OSA. PMID- 26847971 TI - Increased risk of heart failure in women with symptoms of sleep-disordered breathing. AB - BACKGROUND: An association between obstructive sleep apnea and the incidence of heart failure has been reported in men but not in women. The aim of this study was to investigate whether a combination of snoring and excessive daytime sleepiness, the two main symptoms of obstructive sleep apnea syndrome, was able to predict incident heart failure in a population-based sample of women. METHODS: The population-based cohort study Sleep and Health in Women (SHE; n = 5990 women born between 1901 and 1980) was used, with baseline questionnaire data from April 2000 relating to snoring, excessive daytime sleepiness, and covariates. Using data retrieved from the Swedish National Patient Register and Cause of Death Register, the follow-up of incident heart failure continued until 31 December 2011. RESULTS: Among women with both snoring and excessive daytime sleepiness at baseline, 5.3% developed heart failure during follow-up compared with 0.9% in the reference group with neither snoring nor excessive daytime sleepiness. After adjustment for age, waist circumference, smoking, alcohol, hypertension, diabetes, previous myocardial infarction, physical inactivity, depressive symptoms, menopausal status, and hormone replacement therapy, women with the combination of snoring and excessive daytime sleepiness had a twofold increase in the risk of incident heart failure (hazard ratio [HR] 2.2 95% confidence interval [CI] 1.1-4.4). CONCLUSION: Symptoms of obstructive sleep apnea, that is, the combination of snoring and excessive daytime sleepiness, are associated with an increased risk of developing heart failure in women. PMID- 26847972 TI - Benefits and risk of sodium oxybate in idiopathic hypersomnia versus narcolepsy type 1: a chart review. AB - BACKGROUND: Few stimulants have been evaluated for the treatment of idiopathic hypersomnia (IH). Sodium oxybate (indicated in narcolepsy type 1, NT1) has not been tested in IH patients. OBJECTIVE: The aim of this study is to retrospectively evaluate the benefit/risk ratio of sodium oxybate in IH versus NT1 using a chart review. METHODS: We reviewed the files of 46 patients with IH (35.7 +/- 12.6 years old, 78% women) and 47 patients with NT1 (44.1 +/- 18 years old, 47% women) and evaluated the benefits of sodium oxybate using the Epworth sleepiness scale (ESS) and a four-point scale assessing the global benefit, sleep inertia, sleepiness, sleep duration, and sleep onset latency. The spontaneously reported side effects were collected. RESULTS: Sodium oxybate was prescribed at a lower dose in IH than in NT1 (4.3 +/- 2.2 vs. 6.6 +/- 2.8 g/night, p <0.0001) patients after having tried more (3.2 +/- 1.4 vs. 2.2 +/- 1, p <0.0001) stimulants, but it produced a similar ESS change (-3.5 +/- 4.5 vs. -3.2 +/- 4.2 points) in the IH and NT1 groups. Severe morning inertia was improved in 24/34 (71%) patients with IH. During the follow-up period (15.8 months in IH vs. 35 months in NT1 groups), 53% IH and 68% NT1 patients dropped out. The side effects were as frequent in the IH group as in the NT1 group (67% vs. 52%), but nausea (40% vs. 13%) and dizziness (34.3% vs. 4.3%) were more frequent in the IH group. CONCLUSION: The benefit/risk ratio of sodium oxybate in IH- was similar to NT1 associated sleepiness, with additional benefits on severe morning inertia, despite using smaller doses in more refractory patients. PMID- 26847973 TI - The bidirectional relationship between sleep problems and internalizing and externalizing problems in children with ADHD: a prospective cohort study. AB - BACKGROUND: Behavioral sleep problems are common in children with attention deficit hyperactivity disorder (ADHD), and longitudinal studies have found sleep problems to be both a predictor and outcome of internalizing and externalizing problems. We investigated the potential bidirectional relationship between sleep problems and internalizing/externalizing problems. METHODS: Children with ADHD, aged 5-13 years, were recruited from 21 pediatric practices across Victoria, Australia (N = 270). Across a 12-month period, at three time points, parents reported on their child's sleep problems (Children's Sleep Habits Questionnaire) and emotional and behavioral functioning (Strengths and Difficulties Questionnaire). Data were analyzed using autoregressive cross-lagged panel models. RESULTS: Sleep problem severity and emotional/behavioral problem severity were very stable across the 12-month period. Sleep problems at baseline predicted emotional problems at six months (r = 0.17, p < 0.01), and emotional problems at baseline predicted sleep problems at six months (r = 0.07, p < 0.05). However, there was no predictive relationship between sleep problems and emotional problems from 6-12 months. No bidirectional relationship was observed between sleep problems and conduct problems. CONCLUSIONS: In children with ADHD, there is weak evidence of a bidirectional relationship between sleep problems and emotional problems. These symptoms are also very stable over time; therefore, the best treatment approach to improve overall functioning may be to target both sleep and emotional functioning in these children. PMID- 26847974 TI - Sleep-promoting medications in children: physician prescribing habits in Southwestern Ontario, Canada. AB - BACKGROUND: Research indicates that physicians may frequently use pharmacotherapy to treat pediatric insomnia despite minimal safety data and very limited indications. Canadian data on the subject are lacking. This study aimed to determine physicians' views on and prescribing habits for sleep-promoting over the-counter medication (OTCM) and prescription (RXM) medications for children. METHODS: A modified 26-item version of the 'Pediatric Sleep Medication Survey', originally developed by Judith Owens and colleagues, was sent to 100 pediatricians and a random sample of 421 family physicians in Southwestern Ontario, Canada. RESULTS: A total of 67 returned surveys were sufficiently complete for analysis. Sixty-one respondents indicated their specialty (28 pediatricians, 33 family physicians). In a typical 6-month period, 89% and 66% of respondents have recommended OTCM and RXM, respectively, for children with sleep problems. Only 20% have received any formal training on pediatric sleep disorders. The most common circumstances and sleep problems for which OTCM or RXM were recommended were mood disorders, developmental delay and attention deficit hyperactivity disorder (ADHD) (56, 40, and 39%, respectively), and insomnia, bedtime struggles/delayed sleep onset and circadian rhythm disorders (52, 48, and 28%, respectively). A total of 30% recommended OTCM or RXM to otherwise healthy children with sleep problems. Melatonin (73%), OTC antihistamines (41%), antidepressants (37%), and benzodiazepines (29%) were the most commonly recommended OTCM and RXM, respectively. CONCLUSIONS: Respondents in our sample frequently use pharmacotherapy to treat pediatric sleep problems; few have received any training in this area. Our findings indicate the need for evidence based guidelines and regular physician training in the management of pediatric sleep disorders. PMID- 26847975 TI - Sleep quality changes in chronically depressed patients treated with Mindfulness based Cognitive Therapy or the Cognitive Behavioral Analysis System of Psychotherapy: a pilot study. AB - OBJECTIVE: To capture any sleep quality changes associated with group psychotherapy. PATIENTS/METHODS: Physician-referred, chronically depressed patients (n = 25) were randomized to either eight group sessions of Mindfulness based Cognitive Therapy (MBCT, n = 9) plus Treatment As Usual (TAU), or the Cognitive Behavioral Analysis System of Psychotherapy (CBASP, n = 8) plus TAU, or to TAU only (control group, n = 8). Participants recorded their sleep at home. The primary outcome variables were: stable and unstable sleep, which were assessed using cardiopulmonary coupling (CPC) analysis, and estimated total sleep and wake time (minutes). Cardiopulmonary coupling measures heart rate variability and the electrocardiogram's R-wave amplitude fluctuations associated with respiration. RESULTS: By post-treatment night 6, the CBASP group had more stable sleep (p= 0.044) and less wake (p = 0.004) compared with TAU, and less wake vs MBCT (p = 0.039). CONCLUSION: The CBASP group psychotherapy treatment improved sleep quality compared with Treatment As Usual. PMID- 26847976 TI - Sleep disorders increase risk of subsequent erectile dysfunction in individuals without sleep apnea: a nationwide population-base cohort study. AB - BACKGROUND: Sleep disorders (SD) and erectile dysfunction (ED) both play crucial roles in quality of life and have received increasing attention in the general population and among physicians. METHODS: This study investigated the risk of ED in people diagnosed with SD compared with that in age- and sex-matched unaffected people. This longitudinal, nationwide, population-based cohort study was conducted using data in the Taiwan National Health Insurance Research Database (NHIRD) from January 1998 to December 2011. The sample consisted of 603 people with sleep apnea, 17,182 people with non-apnea SD, and 35,570 matched comparisons as controls. A Cox proportional hazard regression was used to compute the risk of ED in people with SD relative to that in people without SD. RESULTS: The ED incidences were 9.44-fold higher (95% CI 6.49-13.7) in the sleep apnea cohort and 3.72-fold higher (95% CI 3.13-4.41) in the non-apnea SD cohort than in the control cohort, respectively, after age, sex, and comorbidities were adjusted for. The incidence of ED was higher in younger adults (adjusted hazard ratio (HR), 10.4 (95% CI 5.93-18.4) in the sleep apnea cohort and adjusted HR, 4.20 (95% CI 3.07-5.76) in non-apnea SD cohort) and those using benzodiazepine (adjusted HR, 9.69 (95% CI 5.48-10.6) in the sleep apnea cohort and adjusted HR, and 3.83 (95% CI 3.20-4.59) in the non-apnea SD cohort). CONCLUSION: This nationwide population-based cohort study provides evidence that people with SD, particularly those with sleep apnea, exhibit an increased risk of subsequent ED. PMID- 26847977 TI - Sleep quality and cognitive decline in a community of older adults in Daqing City, China. AB - OBJECTIVES: To examine the association between self-reported sleep quality and cognitive decline one year later. PATIENTS/METHODS: A longitudinal study of 1010 cognitively intact adults, aged 65-80 years at baseline, from two urban communities in China was performed. Sleep quality at baseline was measured using the Pittsburgh Sleep Quality Index (PSQI). Cognitive function was determined by using the Chinese version of Mini-Mental State Examination (CMMSE) at the baseline and one year later. Substantial CMMSE decline was defined as the CMMSE score decreases by three or more points during the follow-up. Potential confounders, such as age, sex, education, baseline CMMSE score, depression, physical activity level, drinking status, smoking status, body mass index, snoring frequency, history of hypertension, diabetes, and coronary heart disease were measured via questionnaires or physical examination. RESULTS: After adjusting for potential confounders, individuals with poor sleep quality (PSQI > 7), relative to whose with good sleep quality, had 0.32 (95% CI: -0.62, -0.02; p = 0.04) CMMSE-points more decline and tended to have a higher likelihood of developing substantial CMMSE decline (OR = 1.46; 95% CI: 0.97, 2.18; p = 0.06). Among seven subscales of the PSQI, poor sleep efficiency was associated with greater CMMSE decline (beta = -0.16, 95% CI: -0.29, -0.03; p = 0.01) and higher risk of substantial CMMSE decline (OR = 1.24, 95% CI: 1.05, 1.46; p = 0.01). Short sleep duration (sleeping <=5 h/night) was also significantly associated with more CMMSE decline and a higher likelihood of developing substantial CMMSE decline (p <0.05 for both). CONCLUSIONS: Self-reported poor sleep quality may be an indicator of early cognitive decline for elderly people and should be paid particular attention by clinicians. PMID- 26847978 TI - Bed-sharing and related factors in early adolescents. AB - OBJECTIVE: To investigate the prevalence of bed-sharing and examine correlates of bed-sharing habits in early adolescents. METHODS: Participants were 1452 early adolescents from 10 primary schools in Shanghai, China. Children's health status and past history, family environment and parents' attitude towards bed-sharing, and children's sleep arrangements were surveyed. Sleep was assessed by the Children's Sleep Habit Questionnaire. Tanner stage was determined by the endocrinologist. RESULTS: The median of age was 10.83 years (range: 9.42-12.92; 95% confidence interval [CI]: 10.79-10.83) and boys accounted for 51.17%. The prevalence of bed-sharing was 16.8%. Positive parental attitude toward bed sharing (OR: 9.87; 95% CI: 6.57-14.83), asthma (OR: 2.15; 95% CI: 1.16-3.98), smaller residential space (OR: 1.90; 95% CI: 1.17-3.09), extended family (OR: 1.59; 95% CI: 1.16-2.18), and being physically less mature (OR: 2.39; 95% CI: 1.16-4.91) increased the likelihood of bed-sharing. Bed-sharers were more likely to have bedtime resistance (OR: 12.20; 95% CI: 8.59-17.33), sleep anxiety (OR: 3.76; 95% CI: 2.74-5.15), and poor sleep quality (OR: 3.21; 95% CI: 2.28-4.81) compared to non-bed-sharers. Furthermore, bed-sharing was associated with daytime sleepiness (OR: 1.53; 95% CI: 1.10-2.13) but not with sleep duration. CONCLUSIONS: Bed-sharing is highly prevalent among Chinese early adolescents and is significantly related to sleep quality. Parental positive attitude toward bed sharing was the most determining factor. PMID- 26847979 TI - Annual longitudinal survey at up to five time points reveals reciprocal effects of bedtime delay and depression/anxiety in adolescents. AB - OBJECTIVE: To investigate the longitudinal relationship between sleep habits and mental health in adolescents. METHODS: Multipoint observation data of up to five years were employed from a prospective cohort study of sleep habits and mental health status conducted from 2009 to 2013 in a unified junior and senior high school (grades 7-12) in Tokyo, Japan. A total of 1078 students answered a self report questionnaire, including items on usual bed and wake-up times on school days, and the Japanese version of the 12-item General Health Questionnaire (GHQ 12). RESULTS: Latent growth model (LGM) analysis, which requires three or more time point data, showed that longitudinal changes in bedtime and GHQ-12 score (or score for depression/anxiety) were significantly and moderately correlated (correlation coefficient = 0.510, p < 0.05). Another result of interest was that, using an autoregressive cross-lagged (ARCL) model, bedtime and the depression/anxiety score had reciprocal effects the following year: ie, bedtime significantly affects the following year's depression/anxiety, and vice versa. In addition, the analysis provided estimates of mutually predicted changes: one-hour bedtime delay may worsen the GHQ-12 score by 0.2 points, and one-point worsening of the score may delay bedtime by 2.2 minutes. CONCLUSIONS: By using up to five multiple time point data, the present study confirms the correlational and reciprocally longitudinal relationship between bedtime delay and mental health status in Japanese adolescents. The results indicate that preventing late bedtime may have a significant effect on improving mental health in adolescents. PMID- 26847980 TI - Self-reported sleep duration and cognitive performance in older adults: a systematic review and meta-analysis. AB - Sleep is important for optimal cognitive functioning across the lifespan. Among older adults (>=55 years), self-reported short and long sleep durations have been repeatedly, albeit inconsistently, reported to elevate the risk for poor cognitive function. This meta-analytic review quantitatively summarizes the risk for poorer cognitive function among short and long sleepers in older adults. Eligible publications were searched online and manually. A total of 35 independent samples (N = 97,264) from 11 cross-sectional and seven prospective cohort studies were included. Pooled odds ratios (OR) with 95% confidence intervals (CI) were derived using random-effects models. Self-reported short and long sleep increased the odds for poor cognitive function by 1.40 (CI = 1.27 1.56) and 1.58 times (CI = 1.43-1.74), respectively. Effect sizes varied across studies and may have been moderated by both study type (cross-sectional and prospective) and cognitive domain assessed. For cross-sectional studies, extreme sleep durations were significantly associated with poorer multiple-domain performance, executive functions, verbal memory, and working memory capacity. Prospective cohort studies revealed the significant long-term impact of short and long sleep on multiple-domain performance only. These findings establish self reported extreme sleep duration as a risk factor for cognitive aging. PMID- 26847981 TI - Alternative treatment of restless legs syndrome: an overview of the evidence for mind-body interventions, lifestyle interventions, and neutraceuticals. AB - Conventional pharmacologic treatment of restless legs syndrome (RLS) may be limited in some people. Up to 65% of patients with RLS regularly use alternative practices for symptom relief. We reviewed the current clinical evidence, and we proposed physiologic basis for various alternative practices for RLS including mind-body interventions (conventional exercise, yoga, and acupuncture), non pharmacologic lifestyle interventions (pneumatic compression devices [PCDs], light therapy, and cognitive-behavioral therapy [CBT]), and neutraceuticals (vitamins, valerian, and Chinese herbs). Based on the available evidence, regular physical activity should be recommended for the treatment of RLS symptoms. Oral iron supplementation should be considered for people with RLS who have low ferritin levels, although criteria to identify probable responders, and optimal formulations and durations of treatment are needed. Supplementation for low levels of vitamins E, C, and D could be considered, although evidence specifically in RLS is limited, and it is unclear if levels should routinely be checked in patients with RLS. Insufficient evidence exists for yoga, acupuncture, PCDs, near-infrared light therapy, CBT, valerian, or Chinese herbs, but preliminary studies on each of these suggest that high-quality randomized controlled trials may be warranted to support and verify the data presented. PMID- 26847982 TI - A 'double-whammy': obstructive sleep apnea and impaired arousal. PMID- 26847983 TI - Significant association between systolic and diastolic blood pressure elevations and periodic limb movements in patients with idiopathic restless legs syndrome. AB - OBJECTIVE: A new and unique methodology was developed to evaluate the association between periodic limb movements (PLMs) and nocturnal blood pressure (BP) excursions in patients with restless legs syndrome (RLS). METHODS: All data were collected at baseline of the ENCORE (Effects of Neupro on Cardiovascular Observations in Patients with Restless Legs Syndrome) study, a placebo-controlled polysomnographic study of rotigotine in patients with idiopathic RLS. Continuous beat-by-beat BP and heart rate assessments were performed during a full night of polysomnography. All BP elevations occurring with and without PLMs were systematically identified and analyzed. RESULTS: Patients (n = 89) had a mean total of 508.9 +/- 405.7 PLMs, 788.4 +/- 261.9 systolic BP elevations, and 349.7 +/- 242.9 diastolic BP elevations during the night. Higher time-adjusted frequencies of systolic BP elevations [mean difference (95% confidence interval, CI): 543.0 (487.2, I); p <0.0001] and diastolic BP elevations (205.8 (169.3, I); p <0.0001) were observed with PLMs than without PLMs. A peak in the frequency of PLM onset coincided with BP elevation onset. CONCLUSION: Our methodology allowed the first evaluation of the total number of nocturnal PLM-associated BP elevations occurring in patients with RLS. Our data clearly indicate an interdependence between BP elevations and PLMs, and they have clinical relevance as BP variability is a potential cardiovascular risk factor. PMID- 26847984 TI - Increased frequency and severity of restless legs syndrome in patients with neuromyelitis optica spectrum disorder. AB - OBJECTIVES: To investigate the comorbidity of restless legs syndrome (RLS) and neuromyelitis optica spectrum disorder (NMOSD). METHODS: This study enrolled 159 NMOSD patients and 153 age- and gender-matched healthy controls. All participants completed a questionnaire based on the updated International Restless Legs Syndrome Study Group consensus criteria, the International RLS Severity scale, Epworth Sleepiness Scale, Fatigue Severity Scale, and Pittsburgh Sleep Quality Index, and were subsequently interviewed by a neurologist. The frequency and features of RLS were compared between NMOSD patients and healthy controls. The clinical and radiological characteristics of the NMOSD patients with and without RLS were also compared. RESULTS: The frequency and severity of RLS were significantly higher in NMOSD patients than in healthy controls (p = 0.015 for both) and NMOSD patients with RLS had a longer disease duration and more severe disability than those without RLS. CONCLUSIONS: This study indicated importance of considering RLS in NMOSD patients. PMID- 26847985 TI - Post-traumatic narcolepsy and injury of the ascending reticular activating system. PMID- 26847986 TI - Dietary fish intake and sleep quality: a population-based study. AB - BACKGROUND/OBJECTIVES: Due to the content of omega-3 and vitamin D, fish consumption is likely to be associated with better sleep. However, current data are limited to a single study that is not representative of the population at large. The present study aimed to assess the effects of oily fish consumption on sleep quality in community dwelling adults living in rural coastal Ecuador. METHODS: Atahualpa residents aged >=40 years and who were identified during a door-to-door survey were interviewed with field instruments directed at assessing cardiovascular risk factors, sleep quality, and fish consumption. Using parametric regression and generalized linear models adjusted for demographics and cardiovascular risk factors, the study evaluated whether oily fish consumption is associated with a lower Pittsburgh sleep quality index (PSQI). RESULTS: Out of 721 eligible people, 677 (94%) were enrolled. Mean oily fish consumption was 9 +/ 6 servings per week (one serving = 140 grams). Poor sleep quality was noticed in 187 (28%) individuals. Oily fish intake was higher in individuals with good sleep quality (p = 0.013). There was an inverse association between the PSQI score and oily fish servings per week in both parametric regression (beta = -0.040; 95% CI 0.690 to -0.011, p = 0.007) and the adjusted generalized linear model (beta = 0.032; 95% CI -0.605 to -0.004, p = 0.025). CONCLUSIONS: Oily fish consumption is associated with better sleep quality. Even in people who ingest more than the recommended amount of fish, an increase in fish intake is associated with further improvement in the quality of sleep. PMID- 26847987 TI - Effect of valproate on the sleep microstructure of juvenile myoclonic epilepsy patients - a cross-sectional CAP based study. AB - OBJECTIVE: Studies looking at the effect of anti-epileptic medications on sleep microstructure of patients with epilepsy are almost non-existent. The aim of this study was to compare sleep microstructural characteristics of drug-naive juvenile myoclonic epilepsy (JME) patients with those on valproate (VPA) monotherapy. METHODS: Three age- (p = 0.287) and gender- (p = 0.766) matched groups (N = 20 in each group): (1) drug-naive JME (mean age: 21.2 +/- 4.06 years; M : F = 9:11); (2) JME on VPA (mean age: 21.85 +/- 4.28 years; M : F = 11:9); (3) healthy controls (mean age: 23.2 +/- 3.82 years; M : F = 9:11) underwent overnight polysomnography. Scoring and analysis of arousals American Sleep Disorders Association (ASDA, 2002), cyclic alternating pattern (CAP) (Terzano et al., 2002) parameters were performed. Comparison of arousal and CAP parameters was performed using one-way ANOVA, followed by pairwise comparisons using Fisher's LSD test (p <= 0.05). RESULTS: Rapid eye movement (REM) arousal indices were higher in JME patients (Group 1 [p = 0.002] and Group 2 [p <0.001]), whereas the overall and NREM arousal indices were comparable between the three groups. CAP rate was higher in JME patients as compared to controls (p <0.001). Duration of phase A and its subtypes (p <0.001) was reduced in drug-naive patients as compared to VPA group and controls. Finally, percentage of phase A1 (p = 0.003) was decreased and A3 (p = 0.045) was increased in drug-naive patients as compared to VPA group and controls. CONCLUSIONS: We found significant alterations in REM arousal indices and several CAP parameters in JME patients. However, many of these alterations were not seen in the valproate group. This might indicate that anti-epileptic medications such as valproate may beneficially modulate arousal instability in JME patients, and hence promote sleep quality and continuity. PMID- 26847988 TI - Loss of REM sleep features across nighttime in REM sleep behavior disorder. AB - OBJECTIVES: Melatonin is a chronobiotic treatment which also alleviates rapid eye movement (REM) sleep behavior disorder (RBD). Because the mechanisms of this benefit are unclear, we evaluated the clock-dependent REM sleep characteristics in patients with RBD, whether idiopathic (iRBD) or associated with Parkinson's Disease (PD), and we compared findings with PD patients without RBD and with healthy subjects. METHODS: An overnight videopolysomnography was performed in ten iRBD patients, ten PD patients with RBD (PD + RBD+), ten PD patients without RBD (PD + RBD-), and ten controls. The rapid eye movement frequency per minute (REMs index), the tonic and phasic electromyographic (EMG) activity of the levator menti muscle, and the duration of each REM sleep episode were evaluated. A generalized linear model was applied in each group, with the REM sleep cycle (four ordinal levels) as the dependent variable, as a function of REMs index, REM sleep duration, and tonic and phasic EMG activity. RESULTS: From the first to the fourth sleep cycle, REM sleep duration progressively increased in controls only, REMs index increased in subjects without RBD but not in patients with RBD, whether idiopathic or associated with PD, whereas tonic and phasic EMG activity did not change. CONCLUSIONS: Patients with PD or iRBD lost the physiologic nocturnal increase in REM sleep duration, and patients with RBD (either with or without PD) lost the increase of REMs frequency across the night, suggesting an alteration in the circadian system in RBD. This supports the hypothesis of a direct effect of melatonin on RBD symptoms by its chronobiotic activity. PMID- 26847989 TI - Inter-movement interval as a primary stable measure of periodic limb movements of sleep. AB - AIM: Periodic leg movements in sleep (PLMS) are generally evaluated by the number of events per hour during sleep, but this is an unstable measure with marked nightly variability and also fails to assess the basic periodicity that essentially characterizes these movements. The inter-movement interval (IMI) evaluates a putative biological process producing the period of PLMS. By contrast, the actual number of PLMS reflects the expression of this biological process that would likely be affected by multiple factors, particularly those disrupting sleep. Thus, this study tests the hypothesis that measurement of IMI duration should be more stable over nights in comparison to any measure based on counting the number of movements. IMI approximates a log-normal distribution. This study, therefore, tests the hypothesis that the means of the log IMI are more stable from night 1 (N1) to night 2 (N2) sleep recordings compared with measures of the number of PLMS. METHODS: PLMS/h and IMI were measured for two consecutive nights of full sleep recordings for 29 restless legs syndrome (RLS) patients not being treated and 22 healthy controls without RLS. N1-N2 difference between nights was measured as percent of average for the nights. RESULTS: Mean log IMI showed little nightly variability (mean +/- SD for RLS: 3.6% +/- 3.7, controls: 7.1% +/- 7.0) significantly less p < 0.001) in comparison to PLMS/h (mean +/- SD for RLS: 43.2 +/- 37.1, controls: 63.7 +/- 40.8). The IMI nightly variability was also significantly better than that for the periodicity index. IMI also varied considerably between individuals. CONCLUSION: Mean log IMI is a remarkably stable measure across nights within a subject and shows differences between subjects that may have clinical and biological significance. Because of this consistency, the mean log IMI should be considered as one standard measure of PLMS alongside the PLMS index. PMID- 26847990 TI - Napping and the risk of type 2 diabetes: a population-based prospective study. AB - OBJECTIVE: Some studies indicate an association between napping and increased risk of type 2 diabetes. We studied this prospectively in a sample representative of general population. METHODS: A questionnaire was administered to the Finnish Twin Cohort in 1990 (response rate 77%, age 33-60 years). The study population included 12,244 subjects who replied to the question "Do you sleep during the daytime (take naps)?" with five response alternatives ranging from "no need" to "every or almost every day." Information on incident cases of diabetes was obtained by linkage to nationwide registers. Logistic regression models were used to obtain odds ratios (ORs) (95% confidence intervals) for incident type 2 diabetes risk in 1991-2004 by napping category. Adjustments were made for 11 socio-demographic and lifestyle covariates. For subjects aged 33-45 years at baseline, a questionnaire in 2011 provided information on prevalent diabetes. RESULTS: Thirty-four per cent had no need for napping, and 15% did so on >=3 days weekly. There were 356 incident type 2 diabetes cases during the follow-up. Using the 'no need' category as the reference, the risk of type 2 diabetes was significantly increased only among those napping most frequently [OR 1.86 (1.29 2.67), age- and sex-adjusted]. After adjusting for other covariates, the results were essentially the same, but when adjusted for body mass index, the association decreased (to about 1.3) and was statistically non-significant. Analysis of 2011 self-reported type 2 diabetes was in line with the register data. CONCLUSIONS: Frequent napping is associated with future risk of type 2 diabetes. This association is largely explained by obesity. PMID- 26847991 TI - Nocturnal oxygen therapy in patients with chronic heart failure and sleep apnea: a systematic review. AB - Chronic heart failure (CHF) is a public health problem which affects >2% of the adult population, with high morbidity, mortality, and financial cost. Sleep apnea, prevalent in >50% of patients with CHF, can aggravate vital prognosis due to worsening of heart failure. It is considered that a decrease in the apnea hypopnea load may improve outcomes for those patients. Nocturnal non invasive ventilation can be proposed to treat sleep apnea in this situation, there being few alternatives. The present review concerns the use of nocturnal oxygen therapy (NOT) in patients suffering from both CHF and sleep apnea. The interest of NOT in this situation lies in its ability to reduce the central apnea-hypopnea index and to improve nocturnal oximetry disorders related to sleep apnea. Impact on cardiac contractility, patient tolerance, side effects, and costs of NOT are also approached as well as the underlying mechanisms of NOT. In addition, the results of the SERVE-HF trial have shown an increased death rate in patients with CHF and central sleep apnea and who were treated with adaptive servo-ventilation versus control patients. This may lead to renewed interest in NOT in those patients. PMID- 26847992 TI - Restless legs syndrome and pregnancy or delivery complications in China: a representative survey. AB - OBJECTIVE: To perform a detailed epidemiological study of Chinese women and the relationship between restless legs syndrome (RLS) in pregnancy and any associated complications during delivery. METHODS: A total of 3874 pregnant women (18-40 years) who had delivered babies at The First Affiliated Hospital of Zhengzhou University from May 2011 to May 2014 were enrolled in the study. Using a face-to face interview questionnaire, data were collected pertaining to RLS incidence in pregnancy and any associated complications during delivery. The relationship between RLS frequency and pregnancy or delivery complications was further investigated. RESULTS: Among 12.3% of the eligible participants, RLS prevalence occurred at least weekly. Older pregnant women were more likely to suffer from RLS. Individuals who experienced RLS at least weekly reported a statistically higher frequency of excessive daytime sleepiness and an increased prevalence of hypertension, cardiovascular disease, and preeclampsia compared with those without RLS. CONCLUSION: The study revealed that RLS was frequent in Chinese pregnant women, especially in those with pregnancy or delivery complications such as hypertension, cardiovascular disease, and preeclampsia. Restless legs syndrome was also associated with excessive daytime sleepiness. PMID- 26847994 TI - A longitudinal population-based study of carers of people with psychosis. AB - AIMS: Few studies have examined the experiences of carers of people with psychosis using a representative sample. Aiming to obtain generalisable results concerning carers in the context of increased emphasis on involving carers in Australian mental health service delivery and policy frameworks, this study recruited carers within the second Australian national survey of psychotic disorders (Survey of High Impact Psychosis, SHIP). Given that most SHIP participants had long-term illness and extended relationships with carers, the health and wellbeing of carers as a group were expected to be relatively stable. However, since it is unknown whether carers' health and wellbeing would change, our main aim was to explore change and stability in carers' health and wellbeing and the relationship between any changes experienced by individual carers and corresponding SHIP participants' functioning over time. METHODS: Ninety-eight caregivers of SHIP participants were recruited at baseline and completed validated instruments assessing their health and wellbeing. Seventy-eight carers were re-interviewed at 1-year follow-up. Clinical factors were extracted from the SHIP database. Wilcoxon matched-pairs signed-rank test and t-test were used to analyse changes in variables over time. Cross-lagged analyses were conducted to identify possible causative relationships in changes in SHIP participant and carer variables. RESULTS: A substantial percentage of carers experienced social isolation (28.6%), psychological distress (37.7%) and poorer quality of life than population norms. There were no statistically significant changes between baseline and follow-up scores for almost all carers' health and wellbeing variables, other than a poorer perception of their quality of life in relation to their physical health after 1 year. Cross-lagged analyses suggested that poorer functioning of people with psychosis influenced carers' social isolation, grief and psychological distress. CONCLUSIONS: Findings show that carers' perception of their health and wellbeing did not improve within current mental health service delivery frameworks over time. Carer's persistently poor health and wellbeing suggests a pressing need to enhance services that improve carers' health and wellbeing especially their physical health and the functioning of people with psychosis whom they support. PMID- 26847996 TI - Lanthanide dinuclear complexes constructed from mixed oxygen-donor ligands: the effect of substituent positions of the neutral ligand on the magnetic dynamics in Dy analogues. AB - Two series of lanthanide dinuclear complexes with the general formulae, [Ln(n PNO)(Bza)3(H2O)] {Bza = benzoic acid; n = 3, n-PNO = 3-picoline N-oxide, Dy(1) and Er(2); and n = 4, n-PNO = 4-picoline N-oxide, Nd(3), Eu(4), Gd(5), Tb(6), Dy(7), Er(8) and Y(9)} have been successfully synthesized by the hydrothermal method. Single-crystal X-ray diffraction experiments illustrate that the two series of compounds possess similar carboxylic ligand-bridged dinuclear structure and coordination geometry around the lanthanide ions despite the different methyl substituent positions on the neutral ligand. Comparative studies of the Dy analogues in the static-field measurements reveal only a little difference with a small butterfly-shaped opening for complex 1 and a close hysteresis loop for 7 at 2.0 K. However, systematic investigations of the alternating-current (ac) measurements indicate that the different substituent positions of the picoline N oxide ligand have a significant effect on the magnetic relaxation dynamics. A more substantial suppression of the quantum tunnelling of magnetization (QTM) effect and pronounced slow magnetic relaxation were observed in complex 7 as compared to 1 under both zero and a 1 kOe static field. PMID- 26847993 TI - Next-Generation Molecular Testing of Newborn Dried Blood Spots for Cystic Fibrosis. AB - Newborn screening for cystic fibrosis enables early detection and management of this debilitating genetic disease. Implementing comprehensive CFTR analysis using Sanger sequencing as a component of confirmatory testing of all screen-positive newborns has remained impractical due to relatively lengthy turnaround times and high cost. Here, we describe CFseq, a highly sensitive, specific, rapid (<3 days), and cost-effective assay for comprehensive CFTR gene analysis from dried blood spots, the common newborn screening specimen. The unique design of CFseq integrates optimized dried blood spot sample processing, a novel multiplex amplification method from as little as 1 ng of genomic DNA, and multiplex next generation sequencing of 96 samples in a single run to detect all relevant CFTR mutation types. Sequence data analysis utilizes publicly available software supplemented by an expert-curated compendium of >2000 CFTR variants. Validation studies across 190 dried blood spots demonstrated 100% sensitivity and a positive predictive value of 100% for single-nucleotide variants and insertions and deletions and complete concordance across the polymorphic poly-TG and consecutive poly-T tracts. Additionally, we accurately detected both a known exon 2,3 deletion and a previously undetected exon 22,23 deletion. CFseq is thus able to replace all existing CFTR molecular assays with a single robust, definitive assay at significant cost and time savings and could be adapted to high-throughput screening of other inherited conditions. PMID- 26847995 TI - Association of genetic variations of selenoprotein genes, plasma selenium levels, and prostate cancer aggressiveness at diagnosis. AB - BACKGROUND: Genetic variations in some of the selenoprotein genes, alone or together with an individual's selenium status, may influence risk or progression of prostate cancer. We investigated the impact of genetic variants of selenoproteins on plasma selenium levels and cancer aggressiveness at diagnosis in men with localized prostate cancer (PCa). METHODS: The study cohort comprised 722 patients seen at Dana-Farber Cancer Institute who had localized/locally advanced PCa (i.e., stage T3 or less, N0, and M0) from 1994 to 2001. Fifty-five tagging single nucleotide polymorphisms (SNPs) from six selenoprotein genes (TXNRD1, TXNRD2, SEP15, GPX3, SELENBP1, and SEPP1) were analyzed. Logistic regression is used to examine associations of genotypes and plasma selenium levels with risk of aggressive disease, defined as D'Amico intermediate/high risk categories. Step down permutation was applied to adjust for multiple comparisons. RESULTS: Three hundred and forty-eight patients (48%) had aggressive disease at diagnosis. Two SNPs were associated with cancer aggressiveness at diagnosis (unadjusted P = 0.017 and 0.018, respectively). The odds ratio for aggressive disease in patients carrying TXNRD2 rs1005873-AG/GG genotypes or SELENBP1 rs10788804-AG/AA genotypes was 1.54 (95% CI = 1.08, 2.20) and 1.45 (95% CI = 1.07, 1.98), respectively, compared to TXNRD2 rs1005873-AA or SELENBP1 rs10788804 GG carriers. Four SNPs in TXNRD2 (rs1005873, rs13054371, rs3788310, and rs9606174) and the rs230820 in SEPP1 were associated with plasma selenium levels (unadjusted P < 0.05). Permutation adjusted P-values were not statistically significant for all these comparisons at the cut-off point of 0.05. CONCLUSION: We identified polymorphisms in selenoproteins that may influence the plasma selenium levels and may be associated with the risk of presenting with aggressive PCa in men with localized or locally advanced PCa. These results should be validated in other independent datasets. PMID- 26847998 TI - Enantioselective Hydrogenation of beta,beta-Disubstituted Unsaturated Carboxylic Acids under Base-Free Conditions. AB - An additive-free enantioselective hydrogenation of beta,beta-disubstituted unsaturated carboxylic acids catalyzed by the Rh-(R,R)-f-spiroPhos complex has been developed. Under mild conditions, a wide scope of beta,beta-disubstituted unsaturated carboxylic acids were hydrogenated to the corresponding chiral carboxylic acids with excellent enantioselectivities (up to 99.3% ee). This methodology was also successfully applied to the synthesis of the pharmaceutical molecule indatraline. PMID- 26847999 TI - Cardiac Rehabilitation: The Mandate Grows. PMID- 26847997 TI - CT and clinical findings of peripheral primitive neuroectodermal tumour in children. AB - OBJECTIVE: To describe the clinical, CT and pathological findings of paediatric peripheral primitive neuroectodermal tumours (pPNETs) to enhance the recognition of these rare tumours. METHODS: The clinical, CT and pathological findings of 18 paediatric patients with pPNETs confirmed by biopsy or surgical pathology were retrospectively reviewed. RESULTS: The age of these 18 paediatric patients with pPNETs ranged from 4 months to 15 years, with a mean age of 7.7 years. The lesions of these 18 paediatric patients with pPNETs were located in the head and neck (n = 4), chest (n = 2), abdomen and pelvic cavity (n = 6), spine (n = 3), ilium (n = 2) and femur (n = 1). Immunohistochemical examination revealed Homer Wright rosettes in seven lesions, and 94.4% of lesions showed consistent positive staining for CD99. On plain CT images, the majority of pPNETs showed lesions that were ill-defined (72.2%), irregularly shaped (83.3%), heterogeneous (66.7%) or hypodense masses (94.4%), and together with osteolytic bone destruction when the lesion originated in the bone. Calcifications were found in three lesions. After contrast administration, all soft-tissue masses were persistently enhanced heterogeneously with various cystic or necrotic regions, and 71.4% of them had linear enhancement. 94.4% of soft-tissue masses showed a moderate degree of enhancement. Seven cases had lymph node metastasis at diagnosis. CONCLUSION: Paediatric pPNET can involve any part of the body, and a large, ill-defined, aggressive soft-tissue mass and moderate heterogeneous enhancement with varying cystic regions and linear enhancement, with or without osteolytic bone destruction, on CT images could suggest the diagnosis. ADVANCES IN KNOWLEDGE: Primitive neuroectodermal tumours constitute a rare type of malignant neuroectodermal tumours that have chromosomal translocations identical to Ewing's sarcoma, and reports about radiological characteristics of this disease in children are insufficient. This study has described the clinical features and CT and pathological findings in 18 paediatric patients diagnosed with pPNETs in different locations, as a way to enhance the recognition of these tumours and help to differentiate from other types of paediatric malignant bone and soft tissue tumours. PMID- 26848000 TI - High Exercise Capacity Attenuates the Risk of Early Mortality After a First Myocardial Infarction: The Henry Ford Exercise Testing (FIT) Project. AB - OBJECTIVE: To examine the effect of objectively measured exercise capacity (EC) on early mortality (EM) after a first myocardial infarction (MI). PATIENTS AND METHODS: This retrospective cohort study included 2061 patients without a history of MI (mean age, 62+/-12 years; 38% [n=790] women; 56% [n=1153] white) who underwent clinical treadmill stress testing in the Henry Ford Health System from January 1, 1991, through May 31, 2009, and suffered MI during follow-up (MI event proportion, 3.4%; mean time from the exercise test to MI, 6.1+/-4.3 years). Exercise capacity was categorized on the basis of peak metabolic equivalents (METs) achieved: less than 6, 6 to 9, 10 to 11, and 12 or more METs. Early mortality was defined as all-cause mortality within 28, 90, or 365 days of MI. Multivariable logistic regression models were used to assess the effect of EC on the risk of mortality at each time point post-MI adjusting for baseline demographic characteristics, cardiovascular risk factors, medication use, indication for stress testing, and year of MI. RESULTS: The 28-day EM rate was 10.6% overall, and 13.9%, 10.7%, 6.9%, and 6.0% in the less than 6, 6 to 9, 10 to 11, and 12 or more METs categories, respectively (P<.001). Patients who died were more likely to be older, be less fit, be nonobese, have treated hypertension, and have a longer duration from baseline to incident MI (P<.05). Adjusted regression analyses revealed a decreased risk of EM with increasing EC categories. A 1-MET higher EC was associated with an 8% to 10% lower risk of mortality across all time points (28 days: odds ratio [OR], 0.92; 95% CI, 0.87-0.98; P=.006; 90 days: OR, 0.90; 95% CI, 0.86-0.95; P<.001; 365 days: OR, 0.91; 95% CI, 0.87-0.94; P<.001). CONCLUSION: Higher baseline EC was independently associated with a lower risk of early death after a first MI. PMID- 26848001 TI - Association Between Early Cardiac Rehabilitation and Long-term Survival in Cardiac Transplant Recipients. AB - OBJECTIVE: To determine whether participation in early cardiac rehabilitation (CR) after heart transplant (HTx) affects long-term survival. PATIENTS AND METHODS: A retrospective review was conducted in 201 patients who underwent HTx at Mayo Clinic between June 1, 2000, and July 31, 2013. Patients were excluded with multiorgan transplant, no CR data, and follow-up less than 90 days after HTx. Demographic and exercise data at baseline before HTx were collected. Post HTx exercise capacity, biopsy, CR data, and medications were collected at 1 through 5 and 10 years. RESULTS: Overall survival at 1, 5, and 10 years was 98%, 88%, and 82%, respectively; 29 patients died. Number of CR sessions attended in the first 90 days after HTx predicted survival in multivariate regression, controlling for baseline post-HTx 6-minute walk test (6MWT) results and rejection episodes (hazard ratio, 0.90; 95% CI, 0.82-0.97; P=.007). Additional univariate predictors of survival included pre-HTx 6MWT results, weight at HTx, and body mass index and systolic blood pressure at CR enrollment. Pre-HTx 6MWT results, body mass index, and post-HTx were associated with improvement in peak oxygen consumption. CONCLUSION: This report demonstrates, for the first time, an association between CR and long-term survival in patients after HTx. Further work should clarify the most beneficial aspects of CR. PMID- 26848002 TI - Association of Slopes of Estimated Glomerular Filtration Rate With Post-End-Stage Renal Disease Mortality in Patients With Advanced Chronic Kidney Disease Transitioning to Dialysis. AB - OBJECTIVE: To investigate the association of estimated glomerular filtration rate (eGFR) slopes before dialysis initiation with cause-specific mortality after dialysis initiation. PATIENTS AND METHODS: In this retrospective cohort study of 18,874 US veterans who had transitioned to dialysis from October 1, 2007, through September 30, 2011, we examined the association of pre-end-stage renal disease (ESRD) eGFR slopes with all-cause, cardiovascular, and infection-related mortality during the post-ESRD period over a median follow-up of 2.0 years (interquartile range, 1.1-3.2 years). Associations were examined using Cox models with adjustment for potential confounders. RESULTS: Before the 18,874 patients transitioned to dialysis, 4485 (23.8%), 5633 (29.8%), and 7942 (42.1%) experienced fast, moderate, and slow eGFR decline, respectively, and 814 (4.3%) had increasing eGFR (defined as eGFR slopes of less than -10, -10 to less than 5, -5 to <0, and >=0 mL/min per 1.73 m(2) per year). During the study period, a total of 9744 all-cause, 2702 cardiovascular, and 604 infection-related deaths were observed. Compared with patients with slow eGFR decline, those with moderate and fast eGFR decline had a higher risk of all-cause mortality (adjusted hazard ratio [HR], 1.06; 95% CI, 1.00-1.11; and HR, 1.11; 95% CI, 1.04-1.18, respectively) and cardiovascular mortality (HR, 1.11; 95% CI, 1.01-1.23 and HR, 1.13; 95% CI, 1.00-1.27, respectively). In contrast, increasing eGFR was only associated with higher infection-related mortality (HR, 1.49; 95% CI, 1.03-2.17). CONCLUSION: Rapid eGFR decline is associated with higher all-cause and cardiovascular mortality, and increasing eGFR is associated with higher infection related mortality among incident dialysis cases. PMID- 26848004 TI - Focused Cardiovascular Care for Women: The Need and Role in Clinical Practice. AB - Over the past decade, an emerging clinical research focus on cardiovascular (CV) disease (CVD) risk in women has highlighted sex-specific factors that are uniquely important in the prevention and early detection of coronary atherosclerosis in women. Concurrently, a 30% decrease in the number of female deaths from CVD has been observed. Despite this, CVD continues to be the leading cause of death in women, outnumbering deaths from all other causes combined. Clinical practice approaches that focus on the unique aspects of CV care for women are needed to provide necessary resources for the prevention, diagnosis, and treatment of CVD in women. In addition to increasing opportunities for women to participate in CV research, Women's Heart Clinics offer unique settings in which to deliver comprehensive CV care and education, ensuring appropriate diagnostic testing, while monitoring effectiveness of treatment. This article reviews the emerging need and role of focused CV care to address sex-specific aspects of diagnosis and treatment of CVD in women. PMID- 26848003 TI - Centromedian-Parafascicular Complex Deep Brain Stimulation for Tourette Syndrome: A Retrospective Study. AB - Deep brain stimulation (DBS) of the thalamic centromedian/parafascicular (CM-Pf) complex has been reported as a promising treatment for patients with severe, treatment-resistant Tourette syndrome (TS). In this study, safety and clinical outcomes of bilateral thalamic CM-Pf DBS were reviewed in a series of 12 consecutive patients with medically refractory TS, 11 of whom met the criteria of postsurgical follow-up at our institution for at least 2 months. Five patients were followed for a year or longer. Consistent with many patients with TS, all patients had psychiatric comorbidities. Tic severity and frequency were measured by using the Yale Global Tic Severity Scale (YGTSS) over time (average, 26 months) in 10 subjects. One patient was tested at 2-week follow-up only and thus was excluded from group YGTSS analysis. Final YGTSS scores differed significantly from the preoperative baseline score. The average (n=10) improvement relative to baseline in the total score was 54% (95% CI, 37-70); average improvement relative to baseline in the YGTSS Motor tic, Phonic tic, and Impairment subtests was 46% (95% CI, 34-64), 52% (95% CI, 34-72), and 59% (95% CI, 39-78), respectively. There were no intraoperative complications. After surgery, 1 subject underwent wound revision because of a scalp erosion and wound infection; the implanted DBS system was successfully salvaged with surgical revision and combined antibiotic therapy. Stimulation-induced adverse effects did not prevent the use of the DBS system, although 1 subject is undergoing a trial period with the stimulator off. This surgical series adds to the literature on CM-Pf DBS and supports its use as an effective and safe therapeutic option for severe refractory TS. PMID- 26848005 TI - Advanced Innovations for Pain. AB - Chronic pain represents one of the most important public health problems in terms of both the number of patients afflicted and health care costs. Most patients with chronic pain are treated with medications as the mainstay of therapy, and yet most medically treated patients continue to report ongoing pain. Additionally, adverse effects from pain medications represent a major challenge for clinicians and patients. Spinal cord stimulation and intrathecal drug delivery systems are well-established techniques that have been utilized for over 25 years. Intrathecal drug delivery systems have proven efficacy for a wide variety of intractable pain conditions and fewer adverse effects than systemic medical therapy in patients with refractory cancer-related pain. Spinal cord stimulation is cost-effective and provides improved pain control compared with medical therapy in patients with a variety of refractory pain conditions including complex regional pain syndrome, painful diabetic neuropathy, and chronic radiculopathy. Patients who have intractable pain that has not responded to reasonable attempts at conservative pain care measures should be referred to a qualified interventional pain specialist to determine candidacy for the procedures discussed in this article. PMID- 26848006 TI - Chronic Myelomonocytic Leukemia: Focus on Clinical Practice. AB - Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder with features that overlap those of myelodysplastic syndromes (MDSs) and myeloproliferative neoplasms (MPNs). Chronic myelomonocytic leukemia often results in peripheral blood monocytosis and has an inherent tendency to transform to acute myeloid leukemia. Clonal cytogenetic changes are seen in approximately 30% of patients, and molecular abnormalities are seen in more than 90%. Gene mutations involving TET2 (~60%), SRSF2 (~50%), ASXL1 (~40%), and RAS (~30%) are frequent, with nonsense and frameshift ASXL1 mutations being the only mutations identified thus far to have an independent negative prognostic effect on overall survival. Contemporary molecularly integrated prognostic models (inclusive of ASXL1 mutations) include the Molecular Mayo Model and the Groupe Francais des Myelodysplasies model. Given the lack of formal treatment and response criteria, management of CMML is often extrapolated from MDS and MPN, with allogeneic stem cell transplant being the only curative option. Hydroxyurea and other cytoreductive agents have been used to control MPN-like features, while epigenetic modifiers such as hypomethylating agents have been used for MDS-like features. Given the relatively poor response to these agents and the inherent risks associated with hematopoietic stem cell transplant, newer drugs exploiting molecular and epigenetic abnormalities in CMML are being developed. The creation of CMML-specific response criteria is a much needed step in order to improve clinical outcomes. PMID- 26848007 TI - Perioperative Delirium and Mild Cognitive Impairment. PMID- 26848009 TI - Young Female Patient With a Hepatic Adenoma: Determining Risk for Malignant Transformation. PMID- 26848008 TI - Trichobezoar. PMID- 26848011 TI - Zika virus was transmitted by sexual contact in Texas, health officials report. PMID- 26848012 TI - Process-generated nanoparticles from ceramic tile sintering: Emissions, exposure and environmental release. AB - The ceramic industry is an industrial sector in need of significant process changes, which may benefit from innovative technologies such as laser sintering of ceramic tiles. Such innovations result in a considerable research gap within exposure assessment studies for process-generated ultrafine and nanoparticles. This study addresses this issue aiming to characterise particle formation, release mechanisms and their impact on personal exposure during a tile sintering activity in an industrial-scale pilot plant, as a follow-up of a previous study in a laboratory-scale plant. In addition, possible particle transformations in the exhaust system, the potential for particle release to the outdoor environment, and the effectiveness of the filtration system were also assessed. For this purpose, a tiered measurement strategy was conducted. The main findings evidence that nanoparticle emission patterns were strongly linked to temperature and tile chemical composition, and mainly independent of the laser treatment. Also, new particle formation (from gaseous precursors) events were detected, with nanoparticles <30nm in diameter being formed during the thermal treatment. In addition, ultrafine and nano-sized airborne particles were generated and emitted into workplace air during sintering process on a statistically significant level. These results evidence the risk of occupational exposure to ultrafine and nanoparticles during tile sintering activity since workers would be exposed to concentrations above the nano reference value (NRV; 4*10(4)cm(-3)), with 8-hour time weighted average concentrations in the range of 1.4*10(5)cm(-3) and 5.3*10(5)cm(-3). A potential risk for nanoparticle and ultrafine particle release to the environment was also identified, despite the fact that the efficiency of the filtration system was successfully tested and evidenced a >87% efficiency in particle number concentrations removal. PMID- 26848013 TI - Organic matter in sediment layers of an acidic mining lake as assessed by lipid analysis. Part II: Neutral lipids. AB - Natural neutralization of acidic mining lakes is often limited by organic matter. The knowledge of the sources and degradability of organic matter is crucial for understanding alkalinity generation in these lakes. Sediments collected at different depths (surface sediment layer from 0 to 1 cm and deep sediment layer from 4 to 5cm) from an acidic mining lake were studied in order to characterize sedimentary organic matter based on neutral signature markers. Samples were exhaustively extracted, subjected to pre-chromatographic derivatizations and analyzed by GC/MS. Herein, molecular distributions of diagnostic alkanes/alkenes, terpenes/terpenoids, polycyclic aromatic hydrocarbons, aliphatic alcohols and ketones, sterols, and hopanes/hopanoids were addressed. Characterization of the contribution of natural vs. anthropogenic sources to the sedimentary organic matter in these extreme environments was then possible based on these distributions. With the exception of polycyclic aromatic hydrocarbons, combined concentrations across all marker classes proved higher in the surface sediment layer as compared to those in the deep sediment layer. Alkane and aliphatic alcohol distributions pointed to predominantly allochthonous over autochthonous contribution to sedimentary organic matter. Sterol patterns were dominated by phytosterols of terrestrial plants including stigmasterol and beta-sitosterol. Hopanoid markers with the betabeta-biohopanoid "biological" configuration were more abundant in the surface sediment layer, which pointed to higher bacterial activity. The pattern of polycyclic aromatic hydrocarbons pointed to prevailing anthropogenic input. Pyrolytic makers were likely to due to atmospheric deposition from a nearby former coal combustion facility. The combined analysis of the array of biomarkers provided new insights into the sources and transformations of organic matter in lake sediments. PMID- 26848014 TI - Long-term dynamics of soil chemical properties after a prescribed fire in a Mediterranean forest (Montgri Massif, Catalonia, Spain). AB - This study examines the effects of a prescribed fire on soil chemical properties in the Montgri Massif (Girona, Spain). The prescribed forest fire was conducted in 2006 to reduce understory vegetation and so prevent potential severe wildfires. Soil was sampled at a depth of 0-5cm at 42 sampling points on four separate occasions: prior to the event, immediately after, one year after and nine years after. The parameters studied were pH, electrical conductivity (EC), total carbon (C), total nitrogen (N), available phosphorus (P), potassium (K+), calcium (Ca2+) and magnesium (Mg2+). All parameters (except pH) increased significantly immediately after the fire. One year after burning, some chemical parameters - namely, EC, available P and K+ - had returned to their initial, or even lower, values; while others - pH and total C - continued to rise. Total N, Ca2+ and Mg2+ levels had fallen one year after the fire, but levels were still higher than those prior to the event. Nine years after the fire, pH, total C, total N and available P are significantly lower than pre-fire values and nutrients concentrations are now higher than at the outset but without statistical significance. The soil system, therefore, is still far from being recovered nine years later. PMID- 26848015 TI - Removal of the metal ions from aqueous solutions by nanoscaled low molecular pectin isolated from seagrass Phyllospadix iwatensis. AB - Pectins from sea grasses are considered as promising substances with pronounced metal-binding activity. Due to the high molecular weight and heterogeneous structure, the use of pectins for removal of metal ions is difficult. Technology of directed pectin degradation was developed and homogenous degraded nanoscaled pectin polymers were synthesized. Experimental samples of degraded pectin isolated from Phyllospadix iwatensis were tested for their metal binding activity in comparison with native pectin from this seagrass and commercial citrus pectin. The metal uptake of all pectin compounds was highest within the pH range from 4.0 to 6.0. The Langmuir, Freundlich and BET sorption models were applied to describe the isotherms and constants. Results showed that depolymerized pectin exerts highest lead and cadmium binding activity with pronounced affinity. All pectin compounds were suggested to be favorable sorbents. Therefore, it can be concluded that degraded pectin is a prospective material for creation of metal-removing water treatment systems. PMID- 26848017 TI - Too many options, too little choice in COPD? PMID- 26848016 TI - Impact of an intense rainfall event on soil properties following a wildfire in a Mediterranean environment (North-East Spain). AB - Intense rainfall events after severe wildfires can have an impact on soil properties, above all in the Mediterranean environment. This study seeks to examine the immediate impact and the effect after a year of an intense rainfall event on a Mediterranean forest affected by a high severity wildfire. The work analyses the following soil properties: soil aggregate stability, total nitrogen, total carbon, organic and inorganic carbon, the C/N ratio, carbonates, pH, electrical conductivity, extractable calcium, magnesium, sodium, potassium, available phosphorous and the sodium and potassium adsorption ratio (SPAR). We sampled soils in the burned area before, immediately after and one year after the rainfall event. The results showed that the intense rainfall event did not have an immediate impact on soil aggregate stability, but a significant difference was recorded one year after. The intense precipitation did not result in any significant changes in soil total nitrogen, total carbon, inorganic carbon, the C/N ratio and carbonates during the study period. Differences were only registered in soil organic carbon. The soil organic carbon content was significantly higher after the rainfall than in the other sampling dates. The rainfall event did increase soil pH, electrical conductivity, major cations, available phosphorous and the SPAR. One year after the fire, a significant decrease in soil aggregate stability was observed that can be attributed to high SPAR levels and human intervention, while the reduction in extractable elements can be attributed to soil leaching and vegetation consumption. Overall, the intense rainfall event, other post-fire rainfall events and human intervention did not have a detrimental impact on soil properties in all probability owing to the flat plot topography. PMID- 26848018 TI - A Case Series of Double Sequence Defibrillation. AB - INTRODUCTION: Double Sequence Defibrillation or Double Simultaneous Defibrillation (DSD) is the use of two defibrillators almost simultaneously at their highest allowed energy setting to treat refractory ventricular fibrillation (RVF). One set of pads is placed in the Anterior-Posterior position and the other set of pads is placed in the Anterior-Lateral Position. Both defibrillation buttons are pressed simultaneously. We sought to determine ROSC and survival rates in a large EMS system when DSD is routinely utilized for RVF. METHOD: A retrospective case series was performed of all patients who received DSD from January 1, 2015 to April 30, 2015. During the four month period, we requested physicians to instruct paramedics to use DSD on patients after three refractory episodes of VF. All Advanced Cardiac Life Support (ALS) patients treated by paramedics are discussed via telephone communication with a physician in the system of 100 ALS treated patients per day. RESULTS: From January 1, 2015 to April 1, 2015, a total of 7 patients were treated with DSD. The mean age was 62 (Range: 45-78), with mean resuscitation time of 34.3 minutes before first DSD (Range: 23-48). The mean number of single shocks was 5.4 prior to DSD (Range: 3 9), with a mean of 2 DSD shocks delivered. VF converted after DSD in 5 cases (57.1%). Four patients survived to admission (43%). Three patients survived to discharge with no or minimal neurologic disability (28.6%). The mean Cerebral Performance Category Scale was 3.4 with 1 indicating good cerebral performance and 5 indicating Brain Death. DISCUSSION: The correct amount of energy in joules for VF remains unknown. In this case series, significant patients converted out of VF. The reason for improved VF conversion may be several factors including additional defibrillation vectors, increased energy, more energy across myocardium, and unknown variables. Additional research is underway to determine if routine DSD will result in improved survival compared to standard defibrillation techniques. PMID- 26848019 TI - Precision Medicine: Personalized Proteomics for the Diagnosis and Treatment of Idiopathic Inflammatory Disease. AB - IMPORTANCE: To better characterize posterior uveitis, vitreous samples from 15 patients were subjected to antibody arrays, and the expression levels of 200 human cytokines were evaluated. Expression was analyzed by 1-way analysis of variance (significance at P < .01), unsupervised cluster algorithm, and pathway analysis. OBSERVATIONS: Unbiased clustering of patients, based on their cytokine expression profile, suggested that particular protein networks and molecular pathways are altered in various forms of uveitis. Expression of interleukin 23 (IL-23), IL-1 receptor I (IL-1RI), IL-17R, tissue inhibitors of metalloproteinase 1 and 2 (TIMP-1 and TIMP-2), insulinlike growth factor-binding protein 2 (IGFBP 2), nerve growth factor (b-NGF), platelet-derived growth factor receptor beta polypeptide (PDGFRb), bone morphogenic protein 4 (BMP-4), and stem cell factor (SCF) constituted a common cytokine signature in the vitreous of patients with uveitis. In 1 patient with progressive, idiopathic visual loss, this last-line analysis implicated retinal autoimmunity, a diagnosis that was validated when her serum sample was found to contain antibodies to S-arrestin, a retinal protein and potent cause of autoimmune retinal degeneration. CONCLUSIONS AND RELEVANCE: The analysis identifies a common cytokine signature for posterior uveitis and guides the diagnosis of a patient with idiopathic uveitis. Personalized treatment reversed the visual loss, illustrating how proteomic tools may individualize therapy. PMID- 26848021 TI - Chemo-, Diastereo-, and Enantioselective Iridium-Catalyzed Allylic Intramolecular Dearomatization Reaction of Naphthol Derivatives. AB - An iridium-catalyzed intramolecular asymmetric allylic dearomatization reaction of naphthol derivatives is described. Challenges confronted in this reaction include chemoselectivity between carbon and oxygen atoms as nucleophilic centers, diastereoselectivity when contiguous chiral centers are generated, and enantioselective control for constructing an all-carbon quaternary stereocenter. In the presence of an iridium catalyst generated from [{Ir(dbcot)Cl}2] (dbcot=dibenzocyclooctatetraene) and a new THQphos (tetrahydroquinolinedinaphthophosphoramidite) ligand, various spironaphthalenones were obtained with up to greater than 95:5 C/O selectivity, greater than 95:5 d.r., and 99 % ee, thus providing a general method for the dearomatization of naphthols. PMID- 26848020 TI - Nutrient allocation strategies of woody plants: an approach from the scaling of nitrogen and phosphorus between twig stems and leaves. AB - Allocation of limited nutrients, such as nitrogen (N) and phosphorus (P), among plant organs reflects the influences of evolutionary and ecological processes on functional traits of plants, and thus is related to functional groups and environmental conditions. In this study, we tested this hypothesis by exploring the stoichiometric scaling of N and P concentrations between twig stems and leaves of 335 woody species from 12 forest sites across eastern China. Scaling exponents of twig stem N (or P) to leaf N (or P) varied among functional groups. With increasing latitude, these scaling exponents significantly decreased from >1 at low latitude to <1 at high latitude across the study area. These results suggested that, as plant nutrient concentration increased, plants at low latitudes showed a faster increase in twig stem nutrient concentration, whereas plants at high latitudes presented a faster increase in leaf nutrient concentration. Such shifts in nutrient allocation strategy from low to high latitudes may be controlled by temperature. Overall, our findings provide a new approach to explore plant nutrient allocation strategies by analysing the stoichiometric scaling of nutrients among organs, which could broaden our understanding of the interactions between plants and their environments. PMID- 26848022 TI - Direct synthesis of anilines and nitrosobenzenes from phenols. AB - A one-pot synthesis of anilines and nitrosobenzenes from phenols has been developed using an ipso-oxidative aromatic substitution ((i)SOAr) process. The products are obtained in good yields under mild and metal-free conditions. The leaving group effect on reactions that proceed through mixed quionone monoketals has also been investigated and a predictive model has been established. PMID- 26848023 TI - Piperlongumine exerts cytotoxic effects against cancer cells with mutant p53 proteins at least in part by restoring the biological functions of the tumor suppressor. AB - Piperlongumine (PL), a small molecule alkaloid present in black pepper (Piper longum), has been reported to kill tumor cells irrespective of their p53 gene status, however, the mechanisms involved are unknown. Since p53 is a redox sensitive protein, we hypothesized that the redox imbalance induced by PL may affect the structure and/or function of the mutant p53 protein and promote cell death. We used two human colon cancer cell lines, the HT29 and SW620 which harbor the R273H DNA contact abrogatory mutation in p53. PL treatment induced significant ROS production and protein glutathionylation with a concomitant increase in Nrf-2 expression in both cell lines. Surprisingly, immunoprecipitation with wt-p53 specific antibodies (PAb1620) or direct western blotting showed a progressive generation of wild-type-like p53 protein along with a loss of its mutant counterpart in PL-treated HT29 and SW620 cells. Moreover, the EMSA and DNA-affinity blotting revealed a time-dependent restoration of DNA binding for the mutant p53, which was accompanied by the induction of p53 target genes, MDM2 and Bax. PL, while cytotoxic by itself, also increased the cell killing by many anticancer drugs. In nude mice bearing the HT29 tumors, PL alone (7.5 mg/kg daily) produced a 40% decrease in tumor volume, which was accompanied by diminished intratumoral mutant p53 protein levels. The antitumor efficacy of BCNU or doxorubicin in HT29 xenografts was highly potentiated by PL, followed by expression of apoptotic proteins. These clinically-relevant findings suggest that PL-induced oxidative milieu facilitates a weak functional restoration of mutant p53 through protein glutathionylation and contributes to the increased drug sensitivity. PMID- 26848024 TI - How to make the axillary vein larger? Effect of 90 degrees abduction of the arm to facilitate ultrasound-guided axillary vein puncture. AB - PURPOSE: Placement of central venous catheters by the infraclavicular route can be achieved by ultrasound-guided puncture of the axillary vein. However, in some cases, the axillary vein may be difficult to puncture because it is too deep or too small or because it is collapsing significantly during breathing. The objective of this observational study was to determine the effect of 90 degrees abduction of the arm associated with forward position of the shoulder on axillary vein diameters. MATERIAL AND METHODS: In a group of 30 healthy volunteers and in a group of 40 patients during spontaneous breathing, we used ultrasound to examine the axillary vein, visualizing it in short axis, with the arm at 0 degrees and at 90 degrees abduction, pushing the shoulder forward. RESULTS: The axillary vein was easily identified in 100% of subjects, with relevant variability in terms of depth from the skin, diameter, and tendency to collapse during inspiration. Significant increase of axillary vein diameters was found after 90 degrees abduction in 52 of the 70 cases studied. CONCLUSION: These findings suggest that a 90 degrees abduction of the arm, particularly if associated with a forward position of the shoulder, facilitates the visualization of the axillary vein, making its ultrasound-guided venipuncture easier. PMID- 26848025 TI - Virtual issue by COST Action BM1203 (EU-ROS) "Emerging concepts in redox biology and oxidative stress". PMID- 26848026 TI - Effects of dietary resistant starch content on metabolic status, milk composition, and microbial profiling in lactating sows and on offspring performance. AB - In the present study, the effects of dietary resistant starch (RS) content on serum metabolite and hormone concentrations, milk composition, and faecal microbial profiling in lactating sows, as well as on offspring performance was investigated. Sixteen sows were randomly allotted at breeding to two treatments containing low- and high-RS contents from normal and high-amylose corn varieties, respectively, and each treatment had eight replicates (sows). Individual piglet body weight (BW) and litter size were recorded at birth and weaning. Milk samples were obtained on day 10 after farrowing for composition analysis. On day 2 before weaning, blood and faecal samples were collected to determine serum metabolite and hormone concentrations and faecal microbial populations, respectively. Litter size at birth and weaning were not influenced (p > 0.05) by the sow dietary treatments. Although feeding the RS-rich diet to sows reduced (p = 0.004) offspring birth BW, there was no difference in piglet BW at weaning (p > 0.05). High-RS diet increased (p < 0.05) serum triacylglycerol and nonesterified fatty acid concentrations and milk total solid content, and tended (p = 0.09) to increase milk fat content in lactating sows. Feeding the RS-rich diet to sows increased (p < 0.01) faecal bacterial population diversity. These results indicate that high-RS diets induce fatty acid mobilization and a greater intestinal bacterial richness in lactating sows, as well as a greater nutrient density in maternal milk, without affecting offspring performance at weaning. PMID- 26848027 TI - Enhancer of zeste homolog 2 depletion arrests the proliferation of hepatoblastoma cells. AB - Hepatoblastoma is the most common type of malignant liver tumor in children. While outcomes have been greatly improved in the past decades, the treatment of advanced hepatoblastoma has remained challenging. Enhancer of zeste homologue 2 (EZH2), a member of the polycomb group regulators of gene activity, is amplified and overexpressed in a variety of cancers. However, the role of EZH2 in hepatoblastoma has remained to be fully elucidated. The purpose of the present study was to investigate the expression patterns of EZH2 in hepatoblastoma cells and to assess the anti-cancer effects of EZH2 depletion. Western blot analysis revealed that EZH2 expression was significantly higher in hepatoblastoma specimens compared with that in peri-tumor tissues, while p27 was reduced in hepatoblastoma. Suppression of EHZ2 using lentiviral small hairpin RNA inhibited hepatoblastoma cell proliferation, induced cell cycle arrest in G1 phase and enhanced the expression of G1/S-phase checkpoint protein p27. These results suggested that EZH2 may represent a potential diagnostic marker and therapeutic target for the treatment of hepatoblastoma. PMID- 26848029 TI - Ultrasensitive Detection of Bacteria by Targeting Abundant Transcripts. AB - Molecular detection assays are increasingly becoming routine diagnostic techniques for bacterial infection; however, their sensitivities are restricted by the low concentrations of bacteria in clinical samples. Here, we report a new paradigm for ultrasensitive detection of bacteria. The principle of this approach is that by choosing highly transcribed genes as signature sequences and detecting both DNA and its RNA transcripts, assay sensitivity can be greatly improved. First, signature genes with abundant transcripts were screened by RNA-Seq. We confirmed that RT-PCR efficiently amplifies both DNA and RNA, while PCR amplifies only DNA. Unexpectedly, we found that the RNA extraction efficiency is relatively low, while simplified denaturation was more appropriate for transcript detection. For highly transcribed genes, RT-PCR consistently generated lower cycle threshold (Ct) values than those of PCR. The sensitivity of RT-PCR targeting abundant transcripts could detect quantities as low as one bacterium, which was not possible using PCR. Amplification of different genes among several other common bacteria also confirmed that transcript detection by RT-PCR is more sensitive than is DNA detection by PCR. Therefore, abundant transcript detection represents a universal strategy for ultrasensitive detection of bacteria. PMID- 26848028 TI - Inhibition of miR-29c promotes proliferation, and inhibits apoptosis and differentiation in P19 embryonic carcinoma cells. AB - In our previous study, the upregulation of microRNA (miR)-29c was identified in the mother of a fetus with a congenital heart defect. However, the functional and regulatory mechanisms of miR-29c in the development of the heart remain to be elucidated. In the present study, the role and mechanism of miR-29c inhibition in heart development were investigated in an embryonic carcinoma cell model. Inhibition of miR-29c promoted proliferation, and suppressed the apoptosis and differentiation of P19 cells. It was also demonstrated that Wingless-related MMTV integration site 4 (Wnt4) was a target of miR-29c, determined using bioinformatic analysis combined with luciferase assays. The inhibition of miR-29c stimulated the WNT4/beta-catenin pathway, promoting proliferation of the P19 cells, but suppressing their differentiation into cardiomyocytes. Furthermore, the inhibition of miR-29c promoted the expression of B cell lymphoma-2 and inhibited cell apoptosis. These results demonstrate the significance of miR-29c in the process of cardiac development and suggest that miR-29c dysregulation may be associated with the occurrence of CHD. Thus, miR-29c may have therapeutic potential in the future. PMID- 26848031 TI - Direct anodic hydrochloric acid and cathodic caustic production during water electrolysis. AB - Hydrochloric acid (HCl) and caustic (NaOH) are among the most widely used chemicals by the water industry. Direct anodic electrochemical HCl production by water electrolysis has not been successful as current commercially available electrodes are prone to chlorine formation. This study presents an innovative technology simultaneously generating HCl and NaOH from NaCl using a Mn0.84Mo0.16O2.23 oxygen evolution electrode during water electrolysis. The results showed that protons could be anodically generated at a high Coulombic efficiency (i.e. >= 95%) with chlorine formation accounting for 3 ~ 5% of the charge supplied. HCl was anodically produced at moderate strengths at a CE of 65 +/- 4% together with a CE of 89 +/- 1% for cathodic caustic production. The reduction in CE for HCl generation was caused by proton cross-over from the anode to the middle compartment. Overall, this study showed the potential of simultaneous HCl and NaOH generation from NaCl and represents a major step forward for the water industry towards on-site production of HCl and NaOH. In this study, artificial brine was used as a source of sodium and chloride ions. In theory, artificial brine could be replaced by saline waste streams such as Reverse Osmosis Concentrate (ROC), turning ROC into a valuable resource. PMID- 26848032 TI - B7-H3, B7-H4, Foxp3 and IL-2 expression in cervical cancer: Associations with patient outcome and clinical significance. AB - The aim of this study was to determine the expression of B7-H3, B7-H4, Foxp3 and IL-2 in cervical cancer tissues, and evaluate the corresponding clinical significance. The expression of B7-H3, B7-H4, Foxp3 and IL-2 in 108 cervical cancer specimens was detected using immunohistochemistry, and their relationship with clinicopathologic parameters was determined. B7-H3, B7-H4 and Foxp3 had high levels of expression in cervical cancer cells (72.22, 80.56, and 91.56%, respectively). B7-H3 levels were only significantly associated with tumor size (P=0.013), while B7-H4, Foxp3 and IL-2 levels were significantly associated with International Federation of Gynecology and Obstetrics (FIGO) stage (P=0.023, 0.014 and 0.036, respectively) and tumor size (P=0.045, 0.010 and 0.021, respectively). Their expression levels were not correlated with age, histologic type, differentiation and lymph node metastasis (all P>0.05). Cox regression multivariate analysis confirmed that B7-H3 or B7-H4 overexpression was an independent prognostic factor. In addition, there were significant positive relationships between the expression of B7-H3 and B7-H4 with Foxp3 (P<0.001). In contrast, the expression of B7-H3 and B7-H4 was negatively correlated with IL-2 (P<0.05). B7-H3, B7-H4 and Foxp3 may be useful biomarkers in patients with cervical cancer for predicting treatment. PMID- 26848030 TI - Effects of Obesity Related Genetic Variations on Visceral and Subcutaneous Fat Distribution in a Chinese Population. AB - Genome-wide association studies (GWAS) have uncovered numerous variants associated with body mass index (BMI), waist circumference, and waist-to-hip ratio. Our study aims to investigate how these variants are linked to fat distribution. We genotyped 56 validated variants of BMI, waist circumference, and waist-to-hip ratio in 2958 subjects from Chinese community-based populations and performed linear regression analyses to determine the association with visceral fat area (VFA) and subcutaneous fat area (SFA) imaged by magnetic resonance imaging (MRI). We found rs671 in ALDH2 exhibited the significant associations with VFA and the VFA-SFA ratio in all subjects (P = 9.64 * 10(-5) and 6.54 * 10( 4)). rs17782313 near MC4R for VFA and rs4846567 near LYPLAL1 for SFA were found in females only (P = 2.93 * 10(-4) and 0.0015), whereas rs671 in ALDH2 for VFA and the VFA-SFA ratio was restricted to males (P = 1.75 * 10(-8) and 4.43 * 10( 8)). Given the robust association of rs671 with alcohol consumption, we next demonstrated the primary effects of rs671 on VFA and the VFA-SFA ratio were restricted to drinkers (P = 1.45 * 10(-4) and 4.65 * 10(-3)). Our data implied that variants of MC4R and LYPLAL1 modulated body fat distribution with sexual dimorphism and that alcohol consumption may mediate the impact of the ALDH2 locus on visceral fat in a Chinese population. PMID- 26848033 TI - The European refugee crisis and biological age-Is it right to use skeletal maturity as an estimate of chronological age? PMID- 26848035 TI - Improved Gustatory Sensitivity in Morbidly Obese Patients After Laparoscopic Sleeve Gastrectomy. AB - INTRODUCTION: The reduction in the preferences for sweet and fat containing tastes in obese patients who underwent bariatric surgery was relatively well shown; however, there are only limited data on the changes in the sensitivity of other tastes like sour, salty, and bitter. METHODS: We investigated the changes in gustatory sensitivity of 52 morbidly obese patients (M/F, 22/30; age range, 19 60 years; BMI range, 32.5-63.0 kg/m(2)) after laparoscopic sleeve gastrectomy. The surgery was performed by the same surgeon using 5 ports technique. Gustatory sensitivity was tested preoperatively and 1 and 3 months after the surgery using standardized Taste Strips test. RESULTS: There was a statistically significant improvement in the taste acuity to sweet, sour, salty, and bitter tastants in morbidly obese patients after the laparoscopic sleeve gastrectomy during the follow-up period of 3 months. Median whole test scores of the patients were increased from 11.5 preoperatively to 14 in the first and third months. CONCLUSION: In this study, we were able to show the significant improvement in gustatory sensitivity of morbidly obese patients after laparoscopic sleeve gastrectomy for the first time in literature. PMID- 26848036 TI - Balance Disorders in the Elderly: Does Instability Increase Over Time? AB - OBJECTIVES: To analyze the equilibriometric differences between 2 populations of elderly patients (young elderly and very elderly) with instability induced solely by age. METHODS: Cross-sectional study, with 2 study groups classified according to patient age (cut-points in twenty-fifth and seventy-fifth percentiles of the age of the sample). POPULATION: 64 patients aged 65 years or more. Two groups of 32 subjects were established: group A (people 65 years of age or older but less than 72.6, twenty-fifth percentile) and group B (patients 82.5 years, seventh fifth percentile, or older). Main analyzed variables: timed up-and-go test, sensory organization test of the computerized dynamic posturography, Dizziness Handicap Inventory (DHI), and Short Falls Efficacy Scale-International (FES-I) questionnaires. Student's t test or the Mann-Whitney test were used. RESULTS: The older patients obtain poorer scores in the equilibriometric tests but not in all of them. In the sensory organization test, the older patients make poorer use of visual and vestibular information; they also require more time and steps for the timed up-and-go. With regards to the questionnaires, fear of falling is greater (higher Short FES-I scores) but not subjective perception of disability (DHI scores without differences). CONCLUSIONS: There is a need to establish aged subgroups of elderly patients with instability, adapting therapeutic strategies. PMID- 26848038 TI - Psychometric examination and validation of the aggressive driving scale (ADS). AB - Aggressive driving behavior is an important cause of traffic accidents. Based on the recent view that aggressive driving is one way that trait aggression manifests itself, a growing research area has focused on the development of scales to assess aggressive driving. The aggressive driving scale (ADS) analyzed in the present study consists of 24 items. A sample of 276 participants was analyzed to obtain the factor structure and reliability of the ADS and 67 of them participated in the behavioral experiment in order to examine the construct and predictive validity of the scale. Results indicated a 3-factor structure (interference with other drivers, violations/risk taking, and anger/aggression expression behavior) with high item loadings. The ADS had high internal consistency and test-retest reliability. Construct validity of the ADS was established as the ADS subscale scores correlated significantly with trait measures of anger and aggression. Predictive validity of the ADS was verified as most items were significantly correlated with behavioral measures derived from a driving simulator. The ADS was a significant predictor of behavioral measures both in the simulated environment (i.e., frequency of driving off the road, red light running behavior, frequency of colliding with a vehicle, frequency and distance of over speeding, frequency and distance of central crossing) and reported real world situations (i.e., annual moving violations and accidents). These results suggest that the ADS is a reliable and valid tool in evaluating aggressive driving behavior as the current study provides behavioral support for the effectiveness of the ADS in measuring aggressive driving behavior. Aggr. Behav. 42:313-323, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26848037 TI - Altered gp130 signalling ameliorates experimental colitis via myeloid cell specific STAT3 activation and myeloid-derived suppressor cells. AB - STAT3 regulates the expansion of myeloid-derived suppressor cells (MDSCs) during inflammation, infection and cancer. Hyperactivation of STAT3 in gp130(757F/F) mice is associated with protection from experimental colitis. This study determined mechanisms for this protection and compared this to mice with myeloid specific STAT3-deficiency (LysMcre/STAT3(flox); gp130(757F/F) LysMcre/STAT3(flox)). Acute and chronic colitis was induced and colons were removed for histological, mRNA and protein analysis. Cell populations from spleen, mesenteric lymph node and colon were analyzed for different myeloid cell populations using flow cytometry. Functions of MDSCs and LPS-stimulated peritoneal macrophages were further characterized by in vitro and in vivo assays. Here we show that the resistance to experimental colitis in gp130(757F/F) mice is via myeloid-cell specific STAT3 activation, MDSC expansion and increased production of suppressive and protective cytokines. PMID- 26848039 TI - Quantum dots derived from two-dimensional materials and their applications for catalysis and energy. AB - Quantum dots (QDs) derived from the atomically-thin two-dimensional (2D) sheets (graphene, transition metal dichalcogenide, graphitic carbon nitride, hexagonal boron nitride, and phosphorene) are emerging extraordinary zero-dimensional materials. Covering a broad spectrum of interesting optical, catalytic, electronic, chemical and electrochemical properties, these 2D-QDs promise a wide range of novel applications including imaging, sensing, cancer therapy, optoelectronics, display, catalysis, and energy. In this article, we discuss the synthesis methods and the properties of these 2D-QDs and emphasize their applications in electrocatalysis, photocatalysis, supercapacitors, batteries, and photovoltaics. PMID- 26848040 TI - P120 catenin attenuates the angiotensin II-induced apoptosis of human umbilical vein endothelial cells by suppressing the mitochondrial pathway. AB - Hypertension impairs the morphological and functional integrity of circulation. Previous research has shown that the loss of endothelial cells (ECs) is a common event in many cardiovascular diseases. p120 catenin (p120ctn) plays an important role in the regulation of inflammatory responses in ECs. However, the functional significance of p120ctn in angiotensin II (AngII)-induced apoptosis of human umbilical vein endothelial cells (HUVECs) had not previously received much scholarly attention. In the present study, using western blot analysis and RT PCR, we found that AngII-induced cell apoptosis was correlated with a significant decrease in p120ctn expression. The effect of AngII on cell viability was measured by CCK-8 assay. Knockdown of p120ctn with small hairpin RNA (shRNA) increased AngII-induced apoptosis of HUVECs, as demonstrated by Annexin V/PI staining and flow cytometric analysis. Knockdown of p120ctn with shRNA also increased cytochrome c release into the cytoplasm, and cleaved caspase-3 and -9 protein expression. These were accompanied by a decrease in the Bcl-2/Bax ratio (Bcl-2 and Bax protein expression were measured by western blot analysis), and in mitochondrial membrane potential, as measured using JC-1. Overexpression of p120ctn with adenovirus produced opposite effects. In the present study, we demonstrated that p120ctn attenuated AngII-induced apoptosis of HUVECs through the mitochondria-dependent pathway, suggesting that p120ctn plays a critical role in protecting ECs against apoptosis during hypertension. PMID- 26848042 TI - Poly (I:C) transfection induces mitochondrial-mediated apoptosis in cervical cancer. AB - Polyinosinic acid:polycytidylic acid, known as poly (I:C), is an analogue of double-stranded RNA, which exhibits direct antitumor effects against several types of cancer. The present study aimed to evaluate the role of poly (I:C) in the apoptosis of cervical cancer cells. The HeLa human cervical cancer cell line was used in the present study, and cell apoptosis was determined following poly (I:C) transfection. Furthermore, the mRNA levels of interferon (IFN)-beta, the production of reactive oxygen species (ROS), DNA damage, mitochondrial membrane potential (?Psim) and the release of cytochrome c, as well as caspase activation, were determined. The effect of IFN-beta on poly (I:C) transfection-mediated apoptosis was also examined by IFN-beta knockdown. The results showed that poly (I:C) transfection markedly induced HeLa apoptosis, increased the protein levels of pro-apoptotic B cell lymphoma-2 (Bcl-2)-associated X protein (Bax) and BH3 interacting-domain death agonist (Bid), and suppressed the protein expression levels of anti-apoptotic Bcl-2 and Survivin. However, poly (I:C) transfection increased the mRNA levels of IFN-beta, induced ROS production and increased the levels of phosphorylated gammaH2A.X, an indicator of DNA damage. In addition, poly (I:C) transfection decreased ?Psim, triggered the release of cytochrome c from the mitochondria to the cytosol, and induced caspase-9 and -3 activation. IFN-beta knockdown decreased the poly (I:C)-induced production of ROS and DNA damage, restored ?Psim and cytochrome c release, and suppressed caspase-9 and -3 activation, thereby suppressing poly (I:C)-mediated apoptosis in the HeLa cells. Together, the results of the present study demonstrated that poly (I:C) transfection induced IFN-beta, contributing to ROS production, DNA damage, and caspase-9 and -3 activation in the HeLa cervical cancer cell line, leading to mitochondrial-mediated apoptosis. PMID- 26848043 TI - Growth of single gold nanofilaments at the apex of conductive atomic force microscope tips. AB - This paper describes a fast and one-step technique to grow single gold filaments at the apex of commercial conductive AFM tips. It is implemented with an atomic force microscope in air with a high relative humidity at room temperature and is based on a bias-assisted electro-reduction of gold ions directly at the tip apex. The technique requires only ad hoc substrates made of a mesoporous silica layer loaded with gold salt deposited on a conductive electrode. It leads to the growth, at the tip apex, of filaments whose length can be monitored and controlled during the growth between tens and hundreds of nanometers and whose radius of curvature can be as low as 3 nm. Made of polycrystalline gold nanostructures, the filaments are chemically and mechanically stable and conductive. PMID- 26848041 TI - Nanoparticle formulations of cisplatin for cancer therapy. AB - The genotoxic agent cisplatin, used alone or in combination with radiation and/or other chemotherapeutic agents, is an important first-line chemotherapy for a broad range of cancers. The clinical utility of cisplatin is limited both by intrinsic and acquired resistance and dose-limiting normal tissue toxicity. That cisplatin shows little selectivity for tumor versus normal tissue may be a critical factor limiting its value. To overcome the low therapeutic ratio of the free drug, macromolecular, liposomal, and nanoparticle drug delivery systems have been explored toward leveraging the enhanced permeability and retention effect and promoting delivery of cisplatin to tumors. Here, we survey recent advances in nanoparticle formulations of cisplatin, focusing on agents that show promise in preclinical or clinical settings. WIREs Nanomed Nanobiotechnol 2016, 8:776-791. doi: 10.1002/wnan.1390 For further resources related to this article, please visit the WIREs website. PMID- 26848044 TI - Bearing witness: a longitudinal integrated cancer care curriculum. AB - BACKGROUND: The Harvard Medical School Cambridge Integrated Clerkship longitudinal cancer curriculum directly facilitates students' engagement with cancer patients to develop a comprehensive understanding of the disease and the patient's experience of illness. Third-year medical students follow newly diagnosed cancer patients over the course of a year, across all disciplines, and make formal presentations to a multidisciplinary forum at the end of the year. The aim of the study was to discover which aspects of longitudinal care were most meaningful to the students themselves. METHOD: Researchers performed a qualitative thematic analysis of students' presentations. Basing the analysis on principles of grounded theory, researchers took an inductive approach using the constant comparative method to discover core themes and to cluster themes into encompassing domains. RESULT: Researchers identified 33 individual themes among 60 presentations, reflecting five major domains: clinical issues; patient characteristics; systems problems; psychosocial response to cancer; and existential decision making. CONCLUSIONS: In this qualitative study of students' year-end final presentations after a year of cancer care experiences, two areas stood out: students perceived the complexities of medical decision making and students considered the impact of psychosocial factors on patients facing this disease over time. Which aspects of longitudinal care were most meaningful to the students(?). PMID- 26848045 TI - Bipartite recognition of target RNAs activates DNA cleavage by the Type III-B CRISPR-Cas system. AB - CRISPR-Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that the target RNA per se induces DNA cleavage by the Cmr complex in vitro. DNA cleavage activity does not depend on cleavage of the target RNA but notably does require the presence of a short sequence adjacent to the target sequence within the activating target RNA (rPAM [RNA protospacer-adjacent motif]). The activated complex does not require a target sequence (or a PAM) in the DNA substrate. Plasmid elimination by the P. furiosus Cmr system also does not require the Csx1 (CRISPR-associated Rossman fold [CARF] superfamily) protein. Plasmid silencing depends on the HD nuclease and Palm domains of the Cmr2 (Cas10 superfamily) protein. The results establish the Cmr complex as a novel DNA nuclease activated by invader RNAs containing a crRNA target sequence and a rPAM. PMID- 26848047 TI - Alkaline in situ transesterification of Aurantiochytrium sp. KRS 101 using potassium carbonate. AB - The aims of this work were to evaluate K2CO3 as a potent alkaline catalyst for in situ transesterification of Aurantiochytrium sp. KRS 101, one step process in which oil extraction and conversion take place together. This K2CO3-based in situ transesterification was optimized in terms of recovery yield of fatty acid methyl esters (FAMEs) by way of varying biomass concentration, reaction temperature, reaction time, and catalyst concentration. The optimal condition was achieved at 50g/L of biomass concentration and 1% of K2CO3 in the methanol, 25 degrees C of reaction temperature, and 5min of reaction time, resulting in the FAME recovery yield over 90%. It was found that K2CO3 performed better than any other tested catalysts including acids, supporting the notion that K2CO3 is a promising catalyst, especially for in situ transesterification. PMID- 26848046 TI - RNA-activated DNA cleavage by the Type III-B CRISPR-Cas effector complex. AB - The CRISPR (clustered regularly interspaced short palindromic repeat) system is an RNA-guided immune system that protects prokaryotes from invading genetic elements. This system represents an inheritable and adaptable immune system that is mediated by multisubunit effector complexes. In the Type III-B system, the Cmr effector complex has been found to cleave ssRNA in vitro. However, in vivo, it has been implicated in transcription-dependent DNA targeting. We show here that the Cmr complex from Thermotoga maritima can cleave an ssRNA target that is complementary to the CRISPR RNA. We also show that binding of a complementary ssRNA target activates an ssDNA-specific nuclease activity in the histidine aspartate (HD) domain of the Cmr2 subunit of the complex. These data suggest a mechanism for transcription-coupled DNA targeting by the Cmr complex and provide a unifying mechanism for all Type III systems. PMID- 26848048 TI - Effect of common carp (Cyprinus carpio) TLR9 overexpression on the expression of downstream interferon-associated immune factor mRNAs in epithelioma papulosum cyprini cells. AB - Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that recognize pathogen associated molecular patterns (PAMPs) and play an important role in the antiviral response. To determine the effect of common carp TLR9 (CcTLR9) overexpression on the expression of down-stream interferon associated immune factors in epithelioma papulosum cyprini (EPC) cells, may provide useful information for the further investigation on the anti-virus effect mediated by TLR9 in fish. In this study, we constructed an overexpression vector, pEGFP-N1-CcTLR9, by cloning the CcTLR9 gene and inserting it into an expression vector pEGFP-N1. Both plasmids DNA of pEGFP-N1 and pEGFP-N1-CcTLR9 were transfected into EPC cells, and the expression of IRF3, IRF7, ISG15, Mx1, PKR and Viperin mRNA at 0, 6, 12, 24, 48 and 72h post-transfection were determined by real-time quantitative PCR (Q-PCR). Overexpression of the CcTLR9 gene in EPC cells upregulates the expression of IRF3, IRF7, ISG15, Mx1, PKR, and Viperin mRNA, and this was more significant for Viperin, ISG15, and IRF7, and least significant for PKR. Thus, fish TLR9 activates IRF7 signaling to induce I-IFN secretion and the subsequent upregulation of IFN-stimulated genes. PMID- 26848049 TI - Examination of the in vivo immune response elicited by Chlamydia psittaci in chickens. AB - It has since long been reported that Chlamydia psittaci is endemic in the poultry industry in Belgium as well as in other European Countries. This can lead to major economic losses because of a lowered egg production, higher mortality and carcass condemnation. Nowadays, expensive antibiotic treatments are necessary to reduce mortality rate but this can lead to antibiotic resistance. Moreover, C. psittaci can easily be transmitted from birds to humans through the inhalation of pathogen-containing aerosols derived from feces and eye and nostril secretions. Therefore, the need for an efficient vaccine against C. psittaci is augmenting. However, more research is needed to develop such a vaccine. Knowledge on the immune mechanisms of C. psittaci infections is crucial to understand the pathogenesis of, and immunity to this zoonotic pathogen and to act as a basis for vaccination studies. This study has investigated the in vivo immune response evoked by C. psittaci in his natural host, the chicken. Excretion of C. psittaci, chlamydial antibody detection in sera, blood immune cells and the mRNA expression levels of different cytokines, chemokines and one Toll-like receptor were investigated in different organs (conchae, lungs, airsacs, harderian gland, bursa fabricius and spleen) at different time points post infection (6 h, 24 h, 48 h, 4 d, 6d, 8 d, 10 d, 14 d and 21 d). A higher frequency of cytotoxic CD8(+) T cells and monocytes/macrophages expressing the MHC II molecule were observed in the infected group. Several cytokines and chemokines are significantly upregulated during infection but remarkably also significantly downregulated, especially at late time points. Furthermore, the only Toll-like receptor investigated, TLR4, was also significant upregulated in several organs. This study can contribute on the elucidation on how C. psittaci interact with his host, leading to the developing of targets for effective vaccination and therapeutic strategies for infection. PMID- 26848050 TI - Bovine WC1(+) gammadelta T lymphocytes modify monocyte-derived macrophage responses during early Mycobacterium avium subspecies paratuberculosis infection. AB - Following Mycobacterium avium subspecies paratuberculosis (Map) infection, some calves are apparently able to successfully clear the pathogen whereas others become persistently infected; however the reasons for this remain unknown. The importance of innate immunity, and in particular the role of gammadelta T lymphocytes, during early anti-mycobacterial immune response is recognized but specific mechanisms remain incompletely characterized. The objective of this study was to investigate how bovine WC1(+) gammadelta T lymphocytes mediate macrophage function during early Map infection. To achieve this objective, Map infected monocyte-derived macrophages (MDMs) were co-cultured either in direct contact with, or separated by a semi-permeable membrane from, autologous WC1(+) gammadelta T lymphocytes. Nitrites, IL-17A, IFN-gamma, IL-4 and IL-10 from cell culture supernatants were measured. Expression of CD25 on WC1(+) gammadelta T lymphocytes, expression of MHC-I and MHC-II on MDMs and the viability of Map recovered from MDM cultures 72h after Map infection were also assessed. Map viability was significantly reduced when WC1(+) gammadelta T lymphocytes were co cultured in direct contact with Map-infected MDMs. Both MDMs and WC1(+) gammadelta T lymphocytes generated increased concentrations of IFN-gamma and IL-4 in our system, and MDM/WC1(+) gammadelta T lymphocyte synergism was identified for IFN-gamma production. MDMs but not WC1(+) gammadelta T lymphocytes were a significant source of IL-17A. The presence of WC1(+) gammadelta T lymphocytes was associated with higher expression of MHC-I on MDMs and increased concentration of nitrites in supernatants 72h after Map infection. In conclusion, this study showed that WC1(+) gammadelta lymphocytes had differential effects on Map infected macrophages in vitro. PMID- 26848052 TI - Global mismatch between greenhouse gas emissions and the burden of climate change. AB - Countries export much of the harm created by their greenhouse gas (GHG) emissions because the Earth's atmosphere intermixes globally. Yet, the extent to which this leads to inequity between GHG emitters and those impacted by the resulting climate change depends on the distribution of climate vulnerability. Here, we determine empirically the relationship between countries' GHG emissions and their vulnerability to negative effects of climate change. In line with the results of other studies, we find an enormous global inequality where 20 of the 36 highest emitting countries are among the least vulnerable to negative impacts of future climate change. Conversely, 11 of the 17 countries with low or moderate GHG emissions, are acutely vulnerable to negative impacts of climate change. In 2010, only 28 (16%) countries had an equitable balance between emissions and vulnerability. Moreover, future emissions scenarios show that this inequality will significantly worsen by 2030. Many countries are manifestly free riders causing others to bear a climate change burden, which acts as a disincentive for them to mitigate their emissions. It is time that this persistent and worsening climate inequity is resolved, and for the largest emitting countries to act on their commitment of common but differentiated responsibilities. PMID- 26848051 TI - Measuring elemental time and duty cycle using automated video processing. AB - A marker-less 2D video algorithm measured hand kinematics (location, velocity and acceleration) in a paced repetitive laboratory task for varying hand activity levels (HAL). The decision tree (DT) algorithm identified the trajectory of the hand using spatiotemporal relationships during the exertion and rest states. The feature vector training (FVT) method utilised the k-nearest neighbourhood classifier, trained using a set of samples or the first cycle. The average duty cycle (DC) error using the DT algorithm was 2.7%. The FVT algorithm had an average 3.3% error when trained using the first cycle sample of each repetitive task, and had a 2.8% average error when trained using several representative repetitive cycles. Error for HAL was 0.1 for both algorithms, which was considered negligible. Elemental time, stratified by task and subject, were not statistically different from ground truth (p < 0.05). Both algorithms performed well for automatically measuring elapsed time, DC and HAL. Practitioner Summary: A completely automated approach for measuring elapsed time and DC was developed using marker-less video tracking and the tracked kinematic record. Such an approach is automatic, repeatable, objective and unobtrusive, and is suitable for evaluating repetitive exertions, muscle fatigue and manual tasks. PMID- 26848053 TI - Notch regulation of gastrointestinal stem cells. AB - The gastrointestinal (GI) tract epithelium is continuously replenished by actively cycling stem and progenitor cells. These cell compartments are regulated to balance proliferation and stem cell renewal with differentiation into the various mature cell types to maintain tissue homeostasis. In this topical review we focus on the role of the Notch signalling pathway to regulate GI stem cell function in adult small intestine and stomach. We first present the current view of stem and progenitor cell populations in these tissues and then summarize the studies that have established the Notch pathway as a key regulator of gastric and intestinal stem cell function. Notch signalling has been shown to be a niche factor required for maintenance of GI stem cells in both tissues. In addition, Notch has been described to regulate epithelial cell differentiation. Recent studies have revealed key similarities and differences in how Notch regulates stem cell function in the stomach compared to intestine. We summarize the literature regarding Notch regulation of GI stem cell proliferation and differentiation, highlighting tissue-specific functions to compare and contrast Notch in the stomach and intestine. PMID- 26848054 TI - The Dohner fluorescence in situ hybridization prognostic classification of chronic lymphocytic leukaemia (CLL): the CLL Research Consortium experience. AB - This study revisited the Dohner prognostic hierarchy in a cohort of 1585 well documented patients with chronic lymphocytic leukaemia. The duration of both time to first treatment (TTFT) and overall survival (OS) were significantly longer than observed previously, and this is at least partly due to improved therapeutic options. Deletion 13q remains the most favourable prognostic group with median TTFT and OS from fluorescence in situ hybridization (FISH) testing of 72 months and >12 years, respectively. Deletion 11q had the poorest median TTFT (22 months) and 17p deletion the poorest median OS (5 years). The percentages of abnormal nuclei were significantly associated with differential TTFT for the trisomy 12, 13q and 17p deletion cohorts but not for the 11q deletion cohort. From the date of the first FISH study, patients with >85% 13q deletion nuclei had a notably shorter TTFT (24 months). Patients with <=20% 17p deletion nuclei had longer median TTFT and OS from the date of the first FISH study (44 months and 11 years), and were more likely to be IGHV mutated. PMID- 26848055 TI - A cluster of three cases of botulism due to Clostridium baratii type F, France, August 2015. AB - A cluster of three cases of food-borne botulism due to Clostridium baratii type F occurred in France in August 2015. All cases required respiratory assistance. Consumption of a Bolognese sauce at the same restaurant was the likely source of contamination. Clostridium baratii was isolated both from stool specimens from the three patients and ground meat used to prepare the sauce. This is the second episode reported in France caused by this rare pathogen. PMID- 26848056 TI - A Telomerase-Specific Doxorubicin-Releasing Molecular Beacon for Cancer Theranostics. AB - A molecular beacon-based drug delivery system was designed for both detection of telomerase activity in living cells and telomerase-triggered drug release for precise cancer treatment. This system is composed of a gold nanoparticle core densely packed with FITC-labeled hairpin DNA sequences hybridized with telomerase primers. Molecules of the anticancer drug doxorubicin were intercalated into the stem region of the DNA sequence. The presence of telomerase will elongate the primers, leading to inner chain substitution followed by the release of the FITC fluorescence and the trapped doxorubicin. This molecular beacon could specifically distinguish tumor cells and normal cells based on telomerase activity, precisely release doxorubicin in response to telomerase activity in the tumor cells, and prevent toxicity to normal organs. PMID- 26848057 TI - Predictors of patient responses to ovulation induction with clomiphene citrate in patients with polycystic ovary syndrome experiencing infertility. AB - OBJECTIVE: To identify predictors of clomiphene citrate-induced ovulation in patients with polycystic ovary syndrome (PCOS). METHODS: A prospective observational study of patients 18-40 years of age with PCOS experiencing infertility was conducted at Menoufia University Hospital between January 2011 and January 2013. A range of potential predictors of ovulation were recorded before patients received a 50-mg dose of clomiphene citrate. Following ovulation or no response to increasing clomiphene-citrate doses, correlations between predictors and treatment responses were analyzed. RESULTS: In total, 150 patients with PCOS experiencing infertility were enrolled. Following treatment, 110 (73.3%) patients ovulated. Highly significant differences were observed between treatment responders and non-responders in baseline amenorrhea, body mass index (BMI), waist circumference, total testosterone, anti-Mullerian hormone, fasting insulin, homeostatic model assessment of insulin resistance, and visceral fat area (P<0.001). Significant differences in mean ovarian volume (P<0.009) and ovarian stromal artery pulsatility index (P<0.003) were also observed. Total testosterone was the best individual predictor of clomiphene citrate treatment response. The area under the receiver operating characteristic curve in a multivariate prediction model was 0.98. CONCLUSIONS: A combination of patient amenorrhea, BMI, total testosterone, anti-Mullerian hormone, ovarian volume, ovarian stromal artery pulsatility index, and visceral fat area could be used to predict clomiphene-citrate treatment response in patients with PCOS experiencing infertility. ClinicalTrials.gov: NCT02269306. PMID- 26848058 TI - NOBOX is a strong autosomal candidate gene in Tunisian patients with primary ovarian insufficiency. AB - Premature ovarian insufficiency (POI) affects approximately 1% of women before the age of 40. Genetic contribution is a significant component of POI. In this context, heterozygous mutations in NOBOX, BMP15 and GDF9 have been reported. The objective of our study was to evaluate the prevalence of these genes mutations in 125 unrelated Tunisian patients diagnosed with POI. The screening of NOBOX gene revealed three missense mutations (p.Arg117Trp; p.Gly91Trp and p.Pro619Leu) in eight patients. These mutations were not found in a 200 ethnically matched women without fertility problem. The sequencing of BMP15 and GDF9 gene revealed only previously reported variants. In contrast to previous studies, the prevalence of BMP15 variations is not higher than in the control population. Conversely, 6.4% of the cases present a NOBOX mutations; this high prevalence strengthens the consideration of NOBOX gene as strong autosomal candidate for POI. PMID- 26848059 TI - Corrigendum: Glycan complexity dictates microbial resource allocation in the large intestine. PMID- 26848060 TI - [The value of the kinetics of citrulline andarginine as a prognostic factor in critically ill paediatric patients. Author's reply]. PMID- 26848061 TI - [Retropharyngeal abscess with mediastinal invasion: Exclusive antibiotic treatment]. PMID- 26848063 TI - The Promise of a Warranty. PMID- 26848064 TI - Recognition of Reviewers. PMID- 26848062 TI - Absence of Coronary Artery Calcium Identifies Asymptomatic Diabetic Individuals at Low Near-Term But Not Long-Term Risk of Mortality: A 15-Year Follow-Up Study of 9715 Patients. AB - BACKGROUND: Data regarding coronary artery calcification (CAC) prognosis in diabetic individuals are limited to 5-years follow-up. We investigated the long term risk stratification of CAC among diabetic compared with nondiabetic individuals. METHODS AND RESULTS: Nine thousand seven hundred and fifteen asymptomatic individuals undergoing CAC scoring were followed for a median (interquartile range) of 14.7 (13.9-15.6) years. The incidence density rate and hazard ratios with 95% confidence intervals were used to calculate all-cause mortality. Incremental prognostic utility of CAC was evaluated using the area under the receiver operator characteristic curve and net reclassification improvement. Diabetics (54.7+/-10.8 years; 59.4% male) comprised 8.3% of the cohort (n=810), of which 188 (23.2%) died. For CAC=0, the rate of mortality was similar between diabetic and nondiabetic individuals for the first 5 years (P>0.05), with a nonlinear increased risk of mortality for diabetics after 5 years (P<0.05). The adjusted risk of death for those in the highest (CAC>400) versus the lowest (CAC=0) category of CAC increased by a hazards of 4.64 (95% confidence interval =3.74-5.76) and 3.41 (95% confidence interval =2.22-5.22) for nondiabetic and diabetic individuals, respectively. The presence of CAC improved discrimination (area under the receiver operator characteristic curve range: 0.73 0.74; P<0.01) and reclassification (category-free net reclassification improvement range: 0.53-0.50; P<0.001) beyond conventional risk factors in nondiabetic and diabetic individuals, respectively. CONCLUSIONS: CAC=0 is associated with a favorable 5-year prognosis for asymptomatic diabetic and nondiabetic individuals. After 5 years, the risk of mortality increases significantly for diabetic individuals even in the presence of a baseline CAC=0. PMID- 26848065 TI - Muscle Quality is More Impaired in Sarcopenic Patients With Chronic Obstructive Pulmonary Disease. AB - BACKGROUND: Quadriceps muscle fiber atrophy and a loss of oxidative type I muscle fibers and mitochondrial content often occur in chronic obstructive pulmonary disease (COPD), which adversely affects exercise performance. Sarcopenia is an age-related syndrome characterized by wasting and weakness of muscle mass. We recently showed in a large cohort of patients that COPD-related sarcopenia, in particular in male patients, was not only associated with impaired quadriceps muscle strength but also with decreased exercise performance endurance, which could imply involvement of altered muscle fiber type composition. Hence, we hypothesized that both the fiber atrophy and loss of oxidative muscle fibers are more pronounced in sarcopenic compared with nonsarcopenic patients with COPD. OBJECTIVE: The objective of this study was to investigate quadriceps muscle fiber type characteristics in relation to presence of sarcopenia in patients with COPD and in healthy age-matched controls. DESIGN: For this retrospective cross sectional study, body composition (assessed by dual-energy x-ray absorptiometry) and quadriceps muscle biopsy (fiber type distribution and sizes) data were collected from 45 patients with COPDs (aged 42-77 years) and 52 healthy controls (aged 50-77 years). Sarcopenia was based on assessment of appendicular skeletal muscle mass index. RESULTS: Sarcopenia was found in 5.8% of healthy controls and in 31.1% of patients with COPD (P < .01). The proportion of oxidative type I fibers and size of type IIx muscle fibers were decreased in patients with COPD, and the sarcopenic subgroup showed a further decreased proportion as well as a lower size of type I fibers. CONCLUSIONS: Type I muscle fiber proportion is lower in sarcopenic compared with nonsarcopenic patients with COPD. Longitudinal studies may elucidate if the loss of muscle oxidative phenotype drives or accelerates the process of muscle wasting. PMID- 26848066 TI - Telephone Survey of Infection-Control and Antibiotic Stewardship Practices in Long-Term Care Facilities in Maryland. AB - BACKGROUND: Multidrug-resistant organisms are an emerging and serious threat to the care of patients. Long-term care facilities are considered a reservoir of these organisms partly because of the over-prescribing of antibiotics. Antibiotic use is common in long-term care facilities. Antibiotic stewardship programs have been shown to reduce antibiotic consumption in acute-care facilities. The purpose of our study is to investigate existing infection-control practices and antibiotic stewardship programs in long-term care facilities in Maryland. METHODS: We telephoned the infection-control personnel in 231 long-term care facilities in Maryland between February 2014 and July 2015 and reached 124 facilities (59%). RESULTS: Among the 124 facilities surveyed, there were 14,371 beds and 337 infection-control personnel with basic infection-control training. Close to 20% of facilities use silver- or antimicrobial-impregnated urinary catheters. Most facilities (97%) track urinary tract infections. Although all report to the health department in the case of an outbreak, only 63 (50.8 %) report directly to the Centers for Disease Control and Prevention. About 80% of facilities isolate patients with Clostridium difficile, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococci with acute infections only. Eighty percent of facilities have basic guidance on choice of antibiotic, and 27% have a restricted formulary. Only 25% of facilities have an antibiotic approval process. Thirty-five percent of facilities have training for antibiotics prescribing. However, 17% of facilities did not know whether such training existed. CONCLUSIONS: Antibiotic stewardship programs in long-term care facilities are still in early development stages, but our results demonstrate that the majority of facilities are collecting data on prescribing antibiotics, and a surprising number have antibiotic approval and antibiotics prescribing training. PMID- 26848067 TI - Human herpesvirus 8 establishes a latent infection in prostates of Tobago men resulting in increased macrophage infiltration. AB - BACKGROUND: The Caribbean island of Tobago, which is 97% African ancestry, has one of the highest rates of prostate cancer in the world. We have previously reported that human herpesvirus 8 (HHV-8) infection is significantly associated with prostate cancer in Tobago. In this study, we extend those results testing the hypothesis that HHV-8 seropositive Tobagonian men have a chronic HHV-8 infection in their prostates that is associated with increased inflammation. METHODS: Prostate sections were screened by immunohistochemistry for the expression of HHV-8 proteins K8.1 and LANA-1 and for presence of B cells (CD20) and macrophages (CD68). RESULTS: HHV-8 antigen expression representing lytic and latent infections was seen in 73.9% of prostates from HHV-8 seropositive subjects. Latent infections were seen predominantly in glandular epithelia whereas lytic gene expression was seen mainly in macrophages in prostate stroma. Macrophage infiltrates were significantly increased in sections expressing HHV-8 proteins. CONCLUSION: HHV-8 establishes a chronic latent infection in the prostate, which is associated with an increased macrophage infiltrate. PMID- 26848068 TI - Nonthermal Atmospheric Plasmas in Dental Restoration. AB - It is well known that the service life of contemporary composite restoration is unsatisfactory, and longevity of dentin bonding is one of the major culprits. Bonding is essentially a hybridization process in which dental substrate and adhesive resin interact with each other through an exchange process. Thus, the longevity of dentin bonding can only be improved with enhanced qualities in substrate, adhesive resin, and their interaction within the hybridization zone. This review aims to collect and summarize recent advances in utilizing nonthermal atmospheric plasmas (NTAPs)-a novel technology that delivers highly reactive species in a gaseous medium at or below physiologic temperature-to improve the durability of dentin bonding by addressing these 3 issues simultaneously. Overall, NTAP has demonstrated efficacies in improving a number of critical properties for dentin bonding, including deactivation of oral pathogens, modification of surface chemistry/properties, resin polymerization, improvement in adhesive-dentin interactions, and establishment of auxiliary bonding mechanism. While a few preliminary studies have indicated the benefit of NTAP to bond strength and stability, additional researches are warranted to employ knowledge acquired so far and to evaluate these properties in a systematic way. PMID- 26848069 TI - Plasma of Argon Affects the Earliest Biological Response of Different Implant Surfaces: An In Vitro Comparative Study. AB - The aim of this in vitro study was to evaluate the early cell response and protein adsorption elicited by the argon plasma treatment of different commercially available titanium surfaces via a chair-side device. Sterile disks made of grade 4 titanium (n= 450, 4-mm diameter) with 3 surface topographies (machined, plasma sprayed, and zirconia blasted and acid etched) were allocated to receive 4 testing treatments (2% and 10% protein adsorption and cell adhesion with MC3T3-E1 and MG-63). Furthermore, the specimens were divided to undergo 1) argon plasma treatment (10 W, 1 bar for 12 min) in a plasma reactor, 2) ultraviolet (UV) light treatment for 2 h (positive control group), or 3) no treatment (control group). Pretreatment surface analyses based on a scanning electron microscope and profilometer images were also performed. Profilometric analysis demonstrated that the evaluated specimens perfectly suit the standard parameters. The use of argon plasma was capable of affecting the quantity of proteins adsorbed on the different surfaces, notwithstanding their roughness or topographic features at a low fetal bovine serum concentration (2%). UV light treatment for 2 h attained similar results. Moreover, both the plasma of argon and the UV light demonstrated a significant increase in the number of osteoblasts adherent at 10 min in all tested surfaces. Within its limitations, this in vitro study highlights the potential biological benefits of treating implant surfaces with plasma of argon or UV, irrespective of the roughness of the titanium surface. However, in vivo experiments are needed to confirm these preliminary data and settle the rationale of a treatment that might be clinically relevant in case of bone-reparative deficiencies. PMID- 26848070 TI - Dental Surface Texture Characterization Based on Erosive Tooth Wear Processes. AB - The differential diagnosis of dental wear lesions affects their clinical management. We hypothesized that surface texture parameters can differentiate simulated erosion, abrasion, and erosion-abrasion lesions on human enamel and dentin. This in vitro study comprised 2 parts (both factorial 4 * 2), with 4 lesion types (erosion, abrasion, erosion-abrasion, and sound [no lesion; control]) and 2 substrates (enamel and dentin). Flattened/polished dental specimens were used in part 1, whereas natural dental surfaces were used in part 2. Testing surfaces were evaluated in blind conditions, using average surface roughness (Sa) and the following scale-sensitive fractal analysis parameters: area-scale fractal complexity (Asfc), exact proportion length-scale anisotropy of relief (eplsar), scale of maximum complexity (Smc), and textural fill volume (Tfv). Two-way analyses of variance, followed by Fisher's protected least significant difference tests (alpha = 0.05), were used to evaluate the effects of lesion and substrate. Classification trees were constructed to verify the strength of potential associations of the tested parameters. In part 1,Asfc, Sa, and Tfv were able to differentiate erosion and erosion-abrasion lesions from the sound (no lesion) control in both substrates; only Asfc differentiated erosion and erosion-abrasion enamel lesions (allP< 0.05). The best association of parameters correctly classified up to 84% and 94% of the lesions on enamel and dentin, respectively. In part 2, only Asfc differentiated erosion and erosion abrasion lesions from the sound (no lesion) control in both substrates, whereas eplsar was able to differentiate erosion from erosion-abrasion (allP< 0.05). The association of parameters correctly classified up to 81% and 91% of the lesions in enamel and dentin, respectively.Asfc, Sa, and Tfv were able to differentiate erosion and erosion-abrasion lesions, despite their complicated surface textures. The association of parameters improved the differentiation of lesions for both enamel and dentin in polished or natural surfaces. PMID- 26848071 TI - Predicting Periodontitis at State and Local Levels in the United States. AB - The objective of the study was to estimate the prevalence of periodontitis at state and local levels across the United States by using a novel, small area estimation (SAE) method. Extended multilevel regression and poststratification analyses were used to estimate the prevalence of periodontitis among adults aged 30 to 79 y at state, county, congressional district, and census tract levels by using periodontal data from the National Health and Nutrition Examination Survey (NHANES) 2009-2012, population counts from the 2010 US census, and smoking status estimates from the Behavioral Risk Factor Surveillance System in 2012. The SAE method used age, race, gender, smoking, and poverty variables to estimate the prevalence of periodontitis as defined by the Centers for Disease Control and Prevention/American Academy of Periodontology case definitions at the census block levels and aggregated to larger administrative and geographic areas of interest. Model-based SAEs were validated against national estimates directly from NHANES 2009-2012. Estimated prevalence of periodontitis ranged from 37.7% in Utah to 52.8% in New Mexico among the states (mean, 45.1%; median, 44.9%) and from 33.7% to 68% among counties (mean, 46.6%; median, 45.9%). Severe periodontitis ranged from 7.27% in New Hampshire to 10.26% in Louisiana among the states (mean, 8.9%; median, 8.8%) and from 5.2% to 17.9% among counties (mean, 9.2%; median, 8.8%). Overall, the predicted prevalence of periodontitis was highest for southeastern and southwestern states and for geographic areas in the Southeast along the Mississippi Delta, as well as along the US and Mexico border. Aggregated model-based SAEs were consistent with national prevalence estimates from NHANES 2009-2012. This study is the first-ever estimation of periodontitis prevalence at state and local levels in the United States, and this modeling approach complements public health surveillance efforts to identify areas with a high burden of periodontitis. PMID- 26848072 TI - Video Laryngoscopic Techniques Associated with Intubation Success in a Helicopter Emergency Medical Service System. AB - OBJECTIVES: Video laryngoscopy (VL) is a technical adjunct to facilitate endotracheal intubation (ETI). VL also provides objective data for training and quality improvement, allowing evaluation of the technique and airway conditions during ETI. Previous studies of factors associated with ETI success or failure are limited by insufficient nomenclature, individual recall bias and self-report. We tested whether the covariates in prehospital VL recorded data were associated with ETI success. We also measured association between time and clinical variables. METHODS: Retrospective review was conducted in a non-physician staffed helicopter emergency medical service system. ETI was typically performed using sedation and neuromuscular-blockade under protocolized orders. We obtained process and outcome variables from digitally recorded VL data. Patient characteristics data were also obtained from the emergency medical service record and linked to the VL recorded data. The primary outcome was to identify VL covariates associated with successful ETI attempts. RESULTS: Among 304 VL recorded ETI attempts in 268 patients, ETI succeeded for 244 attempts and failed for 60 attempts (first-pass success rate, 82% and overall success rate, 94%). Laryngoscope blade tip usually moved from a shallow position in the oropharynx to the vallecula. In the multivariable logistic regression analysis, attempt time (p = 0.02; odds ratio [OR] 0.99), Cormack-Lehane view (p < 0.001; OR 0.23), bodily fluids obstructing the view (p = 0.01; OR 0.29), and VL equipment failure (p < 0.001; OR 0.14) were negatively associated with successful attempts. Bodily fluids obstructing the view (p < 0.001; hazard ratio [HR] 0.51), VL equipment failure (p = 0.003; HR 0.42), shallow placement of blade tip within 4 seconds (p < 0.001; HR 0.40), number of forward movements (p < 0.001; HR 0.84), trauma (p = 0.04; HR 0.65), and neurological diagnosis (p = 0.04; HR 0.60) were associated with longer ETI attempt time. CONCLUSIONS: Bodily fluids obstructing the view, equipment problems, higher Cormack-Lehane view, and longer ETI attempt time were negatively associated with successful ETI attempts. Initially shallow blade tip position may associate with longer ETI time. VL is useful for measuring and describing multiple factors of ETI and can provide valuable data. PMID- 26848074 TI - New Isolated-Pentagon-Rule and Skeletally Transformed Isomers of C100 Fullerene Identified by Structure Elucidation of their Chloro Derivatives. AB - High-temperature chlorination of C100 fullerene followed by X-ray structure determination of the chloro derivatives enabled the identification of three isomers of C100 from the fullerene soot, specifically numbers 18, 425, and 417, which obey the isolated pentagon rule (IPR). Among them, isomers C1-C100 (425) and C2-C100 (18) afforded C1-C100 (425)Cl22 and C2-C100 (18)Cl28/30 compounds, respectively, which retain their IPR cage connectivities. In contrast, isomer C2v -C100 (417) gives Cs -C100 (417)Cl28 which undergoes a skeletal transformation by the loss of a C2 fragment, resulting in the formation of a nonclassical (NC) C1 C98 (NC)Cl26 with a heptagon in the carbon cage. Most probably, two nonclassical C1-C100 (NC)Cl18/22 chloro derivatives originate from the IPR isomer C1-C100 (382), although both C1-C100 (344) and even nonclassical C1-C100 (NC) can be also considered as the starting isomers. PMID- 26848073 TI - An accelerated miRNA-based screen implicates Atf-3 in Drosophila odorant receptor expression. AB - The Drosophila olfactory system is highly stereotyped in form and function; olfactory sensory neurons (OSNs) expressing a specific odorant receptor (OR) always appear in the same antennal location and the axons of OSNs expressing the same OR converge on the same antennal lobe glomeruli. Although some transcription factors have been implicated in a combinatorial code specifying OR expression and OSN identity, it is clear other players remain unidentified. In hopes of mitigating the challenges of genome-wide screening, we examined the feasibility of a two-tiered approach comprising a primary "pooling" screen for miRNAs whose tissue-specific over-expression causes a phenotype of interest followed by a focused secondary screen using gene-specific RNAi. Since miRNAs down-regulate their targets, miRNA over-expression phenotypes should be attributable to target loss-of-function. It is the sequence-dependence of miRNA-target pairing that suggests candidates for the secondary screen. Since miRNAs are short, however, miRNA misexpression will likely uncover non-biological miRNA-target relationships. Rather than focusing on miRNA function itself where these non biological relationships could be misleading, we propose using miRNAs as tools to focus a more traditional RNAi-based screen. Here we describe such a screen that uncovers a role for Atf3 in the expression of the odorant receptor Or47b. PMID- 26848075 TI - Chronic Visual Disturbance in a Young Healthy Man. PMID- 26848076 TI - Prognostic implications of diffusion-weighted magnetic resonance imaging in patients with superior sulcus tumors receiving induction chemoradiation therapy. AB - OBJECTIVE: The aim of this study was to evaluate a diffusion-weighted magnetic resonance imaging to represent therapeutic response of induction chemoradiation and outcome in patients with non-small cell lung cancer of the superior sulcus. METHODS: Seventeen patients with non-small cell lung cancer of the superior sulcus (median age, 57 years; range, 44-70 years) received induction chemoradiation, followed by surgery. Diffusion-weighted magnetic resonance imaging of the lesion using b values of 0 and 800 s/mm(2) was acquired before treatment and after induction chemoradiation. Changes in tumoral apparent diffusion coefficient were compared with clinical and histopathological response. Cumulative disease-free survival and proportion of surviving were estimated by the Kaplan-Meier method. Survival of diffusion responders and non-responders were compared by log-rank test. RESULTS: A significant correlation was observed between changes of diffusion response after induction chemoradiation and overall survival. Using a defined threshold of percent increase in mean apparent diffusion coefficient, nine out of 17 patients (53%) were classified as diffusion responders and had a mean increase in mean apparent diffusion coefficient of 40.7 +/- 11.2%, while eight diffusion non-responding patients (47%) had a mean increase of 11.0 +/- 15.5% (P < 0.0001). Significant difference was found in overall survival between diffusion responders and diffusion non-responders (88.9 months versus 20.3 months, P = 0.002). CONCLUSIONS: Diffusion-weighted magnetic resonance imaging represented therapeutic effect and prognosis after induction chemoradiation in patients with non-small cell lung cancer of the superior sulcus. PMID- 26848077 TI - High expression of long non-coding RNA lncRNA-ATB is correlated with metastases and promotes cell migration and invasion in renal cell carcinoma. AB - OBJECTIVE: To investigate the expression pattern of a novel long non-coding ribonucleic acid activated by transforming growth factor beta, long non-coding ribonucleic acid activated by transforming growth factor beta, in renal cell carcinoma tissues among the patients with various clinicopathologic features and to detect the possible role of dysregulated long non-coding RNA-ATB in renal cell carcinoma. METHODS: The expression of long non-coding ribonucleic acid activated by transforming growth factor beta in the renal cell carcinoma tissues and renal cancer cell lines was evaluated by quantitative real-time polymerase chain reaction. The association with clinicopathologic features was analyzed. The effects of long non-coding ribonucleic acid activated by transforming growth factor beta on the renal cell carcinoma cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition were investigated by the loss of-function approach. RESULTS: The expression of long non-coding ribonucleic acid activated by transforming growth factor beta was higher in the renal cell carcinoma tissues and renal cancer cells than in the adjacent non-tumor tissues and normal human proximal tubule epithelial cells HK-2. In addition, the long non coding ribonucleic acid activated by transforming growth factor beta expression was significantly higher in the renal cell carcinoma patients with metastasis. The elevated expression of long non-coding ribonucleic acid activated by transforming growth factor beta was associated with tumor stages, histological grade, vascular invasion, lymph node metastasis and distant metastasis. Notably, we found that long non-coding ribonucleic acid activated by transforming growth factor beta knockdown could (i) inhibit cell proliferation; (ii) trigger apoptosis; (iii) reduce epithelial-to-mesenchymal transition program; (iv) suppress cell migration and invasion. CONCLUSIONS: Our data have shown that long non-coding ribonucleic acid activated by transforming growth factor beta actively functions as a regulator of epithelial-to-mesenchymal transition during renal cell carcinoma metastasis, which suggests that long non-coding ribonucleic acid activated by transforming growth factor beta may be a potential prognostic biomarker and therapeutic target for renal cell carcinoma. PMID- 26848079 TI - Sequence Mining of Comorbid Neurodevelopmental Disorders Using the SPADE Algorithm. AB - OBJECTIVES: Understanding the progression of comorbid neurodevelopmental disorders (NDD) during different critical time periods may contribute to our comprehension of the underlying pathophysiology of NDDs. The objective of our study was to identify frequent temporal sequences of developmental diagnoses in noisy patient data. METHODS: We used a data set of 2810 patients, documenting NDD diagnoses given to them by an NDD expert at a child developmental center during multiple visits at different ages. Extensive preprocessing steps were developed in order to allow the data set to be processed by an efficient sequence mining algorithm (SPADE). RESULTS: The discovered sequences were validated by cross validation for 10 iterations; all correlation coefficients for support, confidence and lift measures were above 0.75 and their proportions were similar. No signifi- cant differences between the distributions of sequences were found using Kolmogorov-Smirnov test. CONCLUSIONS: We have demonstrated the feasibility of using the SPADE algorithm for discovery of valid temporal sequences of comorbid disorders in children with NDDs. The identification of such sequences would be beneficial from clinical and research perspectives. Moreover, these sequences could serve as features for developing a full-fledged temporal predictive model. PMID- 26848078 TI - Ability of contrast-enhanced ultrasonography to determine clinical responses of breast cancer to neoadjuvant chemotherapy. AB - OBJECTIVE: We aimed to determine whether contrast-enhanced ultrasonography can predict the effects of neoadjuvant chemotherapy on breast cancer. METHODS: The clinical responses of 63 consecutive patients with breast cancer (T1-4, N0-1, M0) to neoadjuvant chemotherapy between October 2012 and May 2015 were assessed using contrast-enhanced magnetic resonance imaging, positron emission tomography/computed tomography and contrast-enhanced ultrasonography. Perfusion parameters for contrast-enhanced ultrasonography were created from time-intensity curves based on enhancement intensity and temporal changes to objectively evaluate contrast-enhanced ultrasonography findings. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography, magnetic resonance imaging and positron emission tomography/computed tomography to predict a pathological complete response were compared after confirming the pathological findings of surgical specimens. RESULTS: Twenty-three (36.5%) of the 63 patients achieved pathological complete response. The sensitivity, specificity and accuracy of contrast-enhanced ultrasonography for predicting pathological complete response were 95.7% (82.5-99.2%), 77.5% (69.9-79.5%) and 84.1% (74.5-86.7%). The sensitivity of contrast-enhanced ultrasonography was significantly greater than that of magnetic resonance imaging (95.7 vs. 69.6%, P = 0.047). The specificity and accuracy were significantly greater and tended to be greater, respectively, for contrast-enhanced ultrasonography than positron emission tomography/computed tomography (specificity, 77.5 vs. 52.5%, P = 0.02; accuracy, 84.1 vs. 69.8%, P = 0.057). CONCLUSIONS: Contrast-enhanced ultrasonography might serve as a new diagnostic modality when planning therapeutic strategies for patients with breast cancer after neoadjuvant chemotherapy. PMID- 26848080 TI - Understanding How Bereaved Parents Cope With Their Grief to Inform the Services Provided to Them. AB - Our objective was to develop a rich description of how parents experience their grief in the first year after the death of their child, and how various bereavement follow-up and support services helped them during this time, with the aim of informing follow-up and support services offered to bereaved parents. Our findings situated parents' individual experiences of coping within the social and institutional contexts in which they grieved. In the first year after the death of their child, parents regulated their intense feelings of grief through loss oriented, restoration-oriented, and/or meaning reconstruction strategies. Often, parents' relationships with others and many of the bereavement follow-up and support services helped them in this regard. This article also explores how the results may aid service providers in accompanying parents in a way that optimizes outcomes for these parents. PMID- 26848081 TI - Befriending Everyday Life When Bringing Technology Into the Private Sphere. AB - We present the findings of our phenomenological interview study concerning the meaning of being an autonomous person while dependent on advanced medical technology at home. This was elucidated in the participants' narratives as befriending everyday life when bringing technology into the private sphere. We discovered four constituents of the phenomenon: befriending the lived body, depending on good relationships, keeping the home as a private sphere, and managing time. The most important finding was the overall position of the lived body by means of the illness limiting the control over one's life. We found that the participants wanted to be involved in and have influence over their care to be able to enjoy autonomy. We therefore stress the importance of bringing the patients into the care process as chronic illness will be a part of their everyday life for a long time to come, hence challenging patient autonomy. PMID- 26848082 TI - HIV's Syndemic Links With Mental Health, Substance Use, and Violence in an Environment of Stigma and Disparities in Japan. AB - A syndemics orientation has become a valuable lens through which to understand the complex system dynamics of HIV, HIV's links to other social and health problems, and the design of effective, comprehensive interventions. Using data from a broader ethnographic study of HIV epidemics in the Kansai Region and Tokyo Metropolitan Area of Japan, I found that HIV was synergistically linked with poor mental health, substance use, and violence, suggesting the existence of at least three syndemics. These occurred in an environment of stigma and social and health disparities, particularly for men who have sex with men, transgender persons, immigrants, and people living with HIV. Integrated interventions, led by Japan's HIV nongovernmental organizations and supported by the government, should more aggressively target stigma, which underlies most of the syndemic connections. Quantitative research should build upon the ethnographically derived associations shown here and test whether there are additive syndemic effects. PMID- 26848083 TI - Compositional, Contextual, and Collective Community Factors in Mental Health and Well-Being in Australian Rural Communities. AB - There are disproportionately higher and inconsistently distributed rates of recorded suicides in rural areas. Patterns of rural suicide are well documented, but they remain poorly understood. Geographic variations in physical and mental health can be understood through the combination of compositional, contextual, and collective factors pertaining to particular places. The aim of this study was to explore the role of "place" contributing to suicide rates in rural communities. Seventeen mental health professionals participated in semi structured in-depth interviews. Principles of grounded theory were used to guide the analysis. Compositional themes were demographics and perceived mental health issues; contextual themes were physical environment, employment, housing, and mental health services; and collective themes were town identity, community values, social cohesion, perceptions of safety, and attitudes to mental illness. It is proposed that connectedness may be the underlying mechanism by which compositional, contextual, and collective factors influence mental health and well-being in rural communities. PMID- 26848084 TI - Pathways That Affect Wives' HIV Risk Among Serodiscordant Couples in India: Results From the Positive Jeevan Saathi Study. AB - This study examined factors that mitigate or heighten HIV risk among HIV-negative wives in serodiscordant relationships in Gujarat, India. Grounded theory was used to analyze 46 interviews (23 couples) where husbands were HIV-positive and wives were HIV-negative. A conceptual framework emerged from analysis from which we identified five pathways and four key behaviors: (a) safer sex, (b) no sex, (c) coercive sex, and (d) unprotected sex. Most couples either practiced safe sex or abstained from sex. Factors such as wives' assertiveness, a wife's fear of acquiring HIV, mutual understanding, positive sex communication, and a husband's desire to protect wife influenced safe sex/sexual abstinence. Factors such as desire for children, a husband's alcohol use, and intimate partner violence influenced coercive and unprotected sex. Counseling topics on sex communication, verbal and non-verbal safer sex strategies, as well as addressing intimate partner violence and alcohol use may be important in preventing risk to HIV negative wives. PMID- 26848086 TI - New GPs are offered L20,000 to work in underserved areas. PMID- 26848085 TI - Scrophularia orientalis extract induces calcium signaling and apoptosis in neuroblastoma cells. AB - Effective neuroblastoma (NB) treatments are still limited despite treatment options available today. Therefore, this study attempted to identify novel plant extracts that have anticancer effects. Cytotoxicity and increased intracellular calcium levels were determined using the Sulforhodamine B (SRB) assay and Fluo4 AM (acetoxymethyl) staining and fluorescence microscopy in NB cells in order to screen a library of plant extracts. The current study examined the anticancer effects of a dichloromethane extract from Scrophularia orientalis L. (Scrophulariaceae), a plant that has been used in Traditional Chinese Medicine. This extract contained highly potent agents that significantly reduced cell survival and increased calcium levels in NB cells. Further analysis revealed that cell death induced by this extract was associated with intracellular calcium release, opening of the MPTP, caspase 3- and PARP-cleavage suggesting that this extract induced aberrant calcium signaling that resulted in apoptosis via the mitochondrial pathway. Therefore, agents from Scrophularia orientalis may have the potential to lead to new chemo-therapeutic anticancer drugs. Furthermore, targeting intracellular calcium signaling may be a novel strategy to develop more effective treatments for NB. PMID- 26848087 TI - Cost-effectiveness of community-wide treatment for helminthiasis--Authors' reply. PMID- 26848089 TI - Zika virus outbreak in the Americas: the need for novel mosquito control methods. PMID- 26848088 TI - Cost-effectiveness of community-wide treatment for helminthiasis. PMID- 26848090 TI - Are studies underestimating the effects of sanitation on child nutrition? PMID- 26848091 TI - Are studies underestimating the effects of sanitation on child nutrition?- Authors' reply. PMID- 26848092 TI - Seminal Plasma Characteristics and Expression of ATP-binding Cassette Transporter A1 (ABCA1) in Canine Spermatozoa from Ejaculates with Good and Bad Freezability. AB - The composition of seminal plasma and the localization of the ATP-binding cassette transporter A1 (ABCA1) in spermatozoa from good and bad freezers were compared to frozen-thawed spermatozoa from the same dog. Ejaculates were obtained from 31 stud dogs, and the sperm-rich fraction (SRF) was kept for analysis. One aliquot was used for the analysis of concentration, progressive motility (P; CASA), viability (V; CASA) and leucocyte count, and the analysis was performed by flow cytometry (FITC-PNA/PI), SCSA and HOST. In seminal plasma, concentration of albumin, cholesterol, calcium, inorganic phosphate, sodium, potassium, zinc and copper was measured. Semen smears were prepared and evaluated for the expression of ABCA1. The remainder of each ejaculate was frozen. After thawing, the quality assessment was repeated and further smears were prepared. According to post-thaw semen quality, dogs were assigned to good freezers (n = 20) or bad freezers (n = 11), the latter were defined as < 50% progressive motility and/or > 40% morphologically abnormal sperm and/or < 50% viability. Bad freezers were older than good freezers (5.3 vs 3.4 years, p < 0.05). In bad freezers, the percentage of sperm with ABCA1 signal in the acrosome was lower (26.3% vs 35.7%, p < 0.01) and the percentage of sperm with complete loss of ABCA1 signal higher (46.7% vs 30%, p < 0.01); the percentage of dead spermatozoa was higher (36.1% vs 25.5%, p < 0.05), and the concentration of cholesterol and sodium in seminal plasma was lower than in good freezers (p < 0.05). We conclude that in thawed bad freezer sperm, an increase in acrosome damages coincided with an increased loss of cholesterol transporters and cell death, and a lower cholesterol concentration in seminal plasma. Follow-up studies revealed whether a relation exists between these findings. PMID- 26848093 TI - Maternal transcription of non-protein coding RNAs from the PWS-critical region rescues growth retardation in mice. AB - Prader-Willi syndrome (PWS) is a neurogenetic disorder caused by loss of paternally expressed genes on chromosome 15q11-q13. The PWS-critical region (PWScr) contains an array of non-protein coding IPW-A exons hosting intronic SNORD116 snoRNA genes. Deletion of PWScr is associated with PWS in humans and growth retardation in mice exhibiting ~15% postnatal lethality in C57BL/6 background. Here we analysed a knock-in mouse containing a 5'HPRT-LoxP-Neo(R) cassette (5'LoxP) inserted upstream of the PWScr. When the insertion was inherited maternally in a paternal PWScr-deletion mouse model (PWScr(p /m5'LoxP)), we observed compensation of growth retardation and postnatal lethality. Genomic methylation pattern and expression of protein-coding genes remained unaltered at the PWS-locus of PWScr(p-/m5'LoxP) mice. Interestingly, ubiquitous Snord116 and IPW-A exon transcription from the originally silent maternal chromosome was detected. In situ hybridization indicated that PWScr(p /m5'LoxP) mice expressed Snord116 in brain areas similar to wild type animals. Our results suggest that the lack of PWScr RNA expression in certain brain areas could be a primary cause of the growth retardation phenotype in mice. We propose that activation of disease-associated genes on imprinted regions could lead to general therapeutic strategies in associated diseases. PMID- 26848094 TI - Response of nitric and nitrous oxide fluxes to N fertilizer application in greenhouse vegetable cropping systems in southeast China. AB - It is of great concern worldwide that active nitrogenous gases in the global nitrogen cycle contribute to regional and global-scale environmental issues. Nitrous oxide (N2O) and nitric oxide (NO) are generally interrelated in soil nitrogen biogeochemical cycles, while few studies have simultaneously examined these two gases emission from typical croplands. Field experiments were conducted to measure N2O and NO fluxes in response to chemical N fertilizer application in annual greenhouse vegetable cropping systems in southeast China. Annual N2O and NO fluxes averaged 52.05 and 14.87 MUg N m(-2) h(-1) for the controls without N fertilizer inputs, respectively. Both N2O and NO emissions linearly increased with N fertilizer application. The emission factors of N fertilizer for N2O and NO were estimated to be 1.43% and 1.15%, with an annual background emission of 5.07 kg N2O-N ha(-1) and 1.58 kg NO-N ha(-1), respectively. The NO-N/N2O-N ratio was significantly affected by cropping type and fertilizer application, and NO would exceed N2O emissions when soil moisture is below 54% WFPS. Overall, local conventional input rate of chemical N fertilizer could be partially reduced to attain high yield of vegetable and low N2O and NO emissions in greenhouse vegetable cropping systems in China. PMID- 26848095 TI - Localized Single Frequency Lasing States in a Finite Parity-Time Symmetric Resonator Chain. AB - In this paper a practical case of a finite periodic Parity Time chain made of resonant dielectric cylinders is considered. The paper analyzes a more general case where PT symmetry is achieved by modulating both the real and imaginary part of the material refractive index along the resonator chain. The band-structure of the finite periodic PT resonator chains is compared to infinite chains in order to understand the complex interdependence of the Bloch phase and the amount of the gain/loss in the system that causes the PT symmetry to break. The results show that the type of the modulation along the unit cell can significantly affect the position of the threshold point of the PT system. In all cases the lowest threshold is achieved near the end of the Brillouin zone. In the case of finite PT-chains, and for a particular type of modulation, early PT symmetry breaking is observed and shown to be caused by the presence of termination states localized at the edges of the finite chain resulting in localized lasing and dissipative modes at each end of the chain. PMID- 26848098 TI - Real-time RT-PCR systems for CTC detection from blood samples of breast cancer and gynaecological tumour patients (Review). AB - Cells, which detach from a primary epithelial tumour and migrate through lymphatic vessels and blood stream are called 'circulating tumour cells'. These cells are considered to be the main root of remote metastasis and are correlated to a worse prognosis concerning progression-free and overall survival of the patients. Therefore, the detection of the minimal residual disease is of great importance regarding therapeutic decisions. Many different detection strategies are already available, but only one method, the CellSearch(r) system, reached FDA approval. The present review focusses on the detection of circulating tumour cells by means of real-time PCR, a highly sensitive method based on differences in gene expression between normal and malignant cells. Strategies for an enrichment of tumour cells are mentioned, as well as a large panel of potential marker genes. Drawbacks and advantages of the technique are elucidated, whereas, the greatest advantage might be, that by selection of appropriate marker genes, also tumour cells, which have already undergone epithelial to mesenchymal transition can be detected. Finally, the application of real-time PCR in different gynaecological malignancies is described, with breast cancer being the most studied cancer entity. PMID- 26848096 TI - Evolution of VRN2/Ghd7-Like Genes in Vernalization-Mediated Repression of Grass Flowering. AB - Flowering of many plant species is coordinated with seasonal environmental cues such as temperature and photoperiod. Vernalization provides competence to flower after prolonged cold exposure, and a vernalization requirement prevents flowering from occurring prior to winter. In winter wheat (Triticum aestivum) and barley (Hordeum vulgare), three genes VRN1, VRN2, and FT form a regulatory loop that regulates the initiation of flowering. Prior to cold exposure, VRN2 represses FT. During cold, VRN1 expression increases, resulting in the repression of VRN2, which in turn allows activation of FT during long days to induce flowering. Here, we test whether the circuitry of this regulatory loop is conserved across Pooideae, consistent with their niche transition from the tropics to the temperate zone. Our phylogenetic analyses of VRN2-like genes reveal a duplication event occurred before the diversification of the grasses that gave rise to a CO9 and VRN2/Ghd7 clade and support orthology between wheat/barley VRN2 and rice (Oryza sativa) Ghd7 Our Brachypodium distachyon VRN1 and VRN2 knockdown and overexpression experiments demonstrate functional conservation of grass VRN1 and VRN2 in the promotion and repression of flowering, respectively. However, expression analyses in a range of pooids demonstrate that the cold repression of VRN2 is unique to core Pooideae such as wheat and barley. Furthermore, VRN1 knockdown in B. distachyon demonstrates that the VRN1-mediated suppression of VRN2 is not conserved. Thus, the VRN1-VRN2 feature of the regulatory loop appears to have evolved late in the diversification of temperate grasses. PMID- 26848097 TI - A Picrinine N-Methyltransferase Belongs to a New Family of gamma-Tocopherol-Like Methyltransferases Found in Medicinal Plants That Make Biologically Active Monoterpenoid Indole Alkaloids. AB - Members of the Apocynaceae plant family produce a large number of monoterpenoid indole alkaloids (MIAs) with different substitution patterns that are responsible for their various biological activities. A novel N-methyltransferase involved in the vindoline pathway in Catharanthus roseus showing distinct similarity to gamma tocopherol C-methyltransferases was used in a bioinformatic screen of transcriptomes from Vinca minor, Rauvolfia serpentina, and C. roseus to identify 10 gamma-tocopherol-like N-methyltransferases from a large annotated transcriptome database of different MIA-producing plant species (www.phytometasyn.ca). The biochemical function of two members of this group cloned from V. minor (VmPiNMT) and R. serpentina (RsPiNMT) have been characterized by screening their biochemical activities against potential MIA substrates harvested from the leaf surfaces of MIA-accumulating plants. The approach was validated by identifying the MIA picrinine from leaf surfaces of Amsonia hubrichtii as a substrate of VmPiNMT and RsPiNMT. Recombinant proteins were shown to have high substrate specificity and affinity for picrinine, converting it to N-methylpicrinine (ervincine). Developmental studies with V. minor and R. serpentina showed that RsPiNMT and VmPiNMT gene expression and biochemical activities were highest in younger leaf tissues. The assembly of at least 150 known N-methylated MIAs within members of the Apocynaceae family may have occurred as a result of the evolution of the gamma-tocopherol-like N methyltransferase family from gamma-tocopherol methyltransferases. PMID- 26848100 TI - Optimizing the treatment of rhegmatogenous retinal detachment. AB - Surgical approaches for rhegmatogenous retinal detachment (RRD) have evolved rapidly in the past century. This has resulted in an increase in the anatomical success rate from zero per cent in the beginning of the 1900s to now almost 100 per cent. Rhegmatogenous retinal detachment is regarded as an acute eye disease that needs immediate treatment. With the increasing number of cataract surgeries and an increased elderly population, the numbers of RRD occurrences are increasing. The aim of this thesis is to create knowledge on how treatment and care of RRD patients can be optimized. In the first paper, data on the incidence of RRD in Denmark are presented based on data from a nation register the National Patient Registry (NPR). It was discovered that the incidence of RRD in Denmark is similar to previous reported numbers and that the incidence has been increasing due to increasing numbers of cataract surgeries and an increased elderly population. Using data from the NPR, we estimated that the risk of a RRD occurring on the fellow eye is 100 times larger than on the first eye and that middle aged men have the highest risk. Having an increase in the incidence of RRD we need to ensure that the patients are also treated in the most optimal way. To ensure this, an indicator is needed to monitor the quality at the different centres. This indicator presented in the second paper is based in the occurrence of redetachment. We define a detachment to be caused by poor surgery if the retina detaches within one year after initial surgery with pneumatic retinopexy, scleral buckling and VTX with gas, and one and a half years after surgery with VTX with oil. Also lack of oil removal within the first year is a failed operation. It is widely accepted that RRD is an acute disease but when should surgery be performed to attain the most optimal result? In the third paper, we evaluated the progression of posterior RRD with an optical coherence tomography to make an objective assessment of the movement. We found that the risk of a macula on RRD progressing to affect the fovea is small if the patient is postured appropriately. We found that the movement of the RRD is dynamic but the detachments will ultimately approach the fovea. Having an opportunity to postpone surgery without risking the outcome for the patient allows a more optimal surgery. The results of this thesis can be used by all health care systems to establish optimal conditions in the treatment of RRD. PMID- 26848099 TI - Miltirone exhibits antileukemic activity by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction pathways. AB - In this study, we investigated the effects of miltirone in human leukemia cell lines, primary leukemia cells, and nude mice U937 xenograft. Treatment of cells with miltirone resulted in apoptosis, mitochondria membrane potential (MMP) collapses, increase of Bax/Bcl-2 ratio, and cytochrome c release. Miltirone triggered the endoplasmic reticulum (ER) stress identified through several key molecules of the unfolded protein response, including phosphorylated PERK, eIF2a, GRP78, GRP94, and caspase-12. Miltrone treatment also resulted in the release of Ca(2+) from the ER stores and mitochondrial Ca(2+) loading in the cells. Further research revealed that miltirone resulted in dose-dependent decrease in complex III activity and elevated reactive oxygen species (ROS) production in these cells. Miltirone-induced apoptosis, dissipation of MMP and ER stress were dramatically blocked by pretreatment with antioxidant N-acetylcysteine (NAC). In contrast, treatment with ER stress inhibitor TUDCA significantly attenuated miltirone-induced ROS and apoptosis in leukemia cells. Moreover, our in vivo findings showed that administration of miltirone markedly inhibited tumor growth and induced apoptosis in U937 xenograft model with low systemic toxicity. Taken together, these findings indicate that miltirone may exert its antileukemic activity by inducing apoptosis through a ROS-dependent destructive cycle involving ER stress and mitochondrial dysfunction. PMID- 26848102 TI - Perceptions of low agency and high sexual openness mediate the relationship between sexualization and sexual aggression. AB - Researchers have become increasingly interested in the saturation of popular Western culture by female hypersexualization. We provide data showing that men have more sexually aggressive intentions toward women who self-sexualize, and that self-sexualized women are vulnerable to sexual aggression if two qualifying conditions are met. Specifically, if perceivers view self-sexualized women as sexually open and lacking agency (i.e., the ability to influence one's environment), they harbor more sexually aggressive intentions and view women as easier to sexually victimize. In Experiment 1, male participants viewed a photograph of a woman whose self-sexualization was manipulated through revealing versus non-revealing clothing. In subsequent experiments, men and women (Experiment 2) and men only (Experiment 3) viewed a photograph of a woman dressed in non-revealing clothing but depicted as open or closed to sexual activity. Participants rated their perceptions of the woman's agency, then judged how vulnerable she was to sexual aggression (Experiments 1 and 2) or completed a sexually aggressive intentions measure (Experiment 3). Results indicated that both men and women perceived self-sexualized women as more vulnerable to sexual aggression because they assumed those women were highly sexually open and lacked agency. Perceptions of low agency also mediated the relationship between women's perceived sexual openness and men's intentions to sexually aggress. These effects persisted even when we described the self-sexualized woman as possessing highly agentic personality traits and controlled for individual differences related to sexual offending. The current work suggests that perceived agency and sexual openness may inform perpetrator decision-making and that cultural hypersexualization may facilitate sexual aggression. Aggr. Behav. 42:483-497, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26848101 TI - Non-parametric combination and related permutation tests for neuroimaging. AB - In this work, we show how permutation methods can be applied to combination analyses such as those that include multiple imaging modalities, multiple data acquisitions of the same modality, or simply multiple hypotheses on the same data. Using the well-known definition of union-intersection tests and closed testing procedures, we use synchronized permutations to correct for such multiplicity of tests, allowing flexibility to integrate imaging data with different spatial resolutions, surface and/or volume-based representations of the brain, including non-imaging data. For the problem of joint inference, we propose and evaluate a modification of the recently introduced non-parametric combination (NPC) methodology, such that instead of a two-phase algorithm and large data storage requirements, the inference can be performed in a single phase, with reasonable computational demands. The method compares favorably to classical multivariate tests (such as MANCOVA), even when the latter is assessed using permutations. We also evaluate, in the context of permutation tests, various combining methods that have been proposed in the past decades, and identify those that provide the best control over error rate and power across a range of situations. We show that one of these, the method of Tippett, provides a link between correction for the multiplicity of tests and their combination. Finally, we discuss how the correction can solve certain problems of multiple comparisons in one-way ANOVA designs, and how the combination is distinguished from conjunctions, even though both can be assessed using permutation tests. We also provide a common algorithm that accommodates combination and correction. PMID- 26848103 TI - How to use faecal calprotectin in management of paediatric inflammatory bowel disease. AB - Faecal calprotectin (FC) is a neutrophil-derived protein released in stool in response to mucosal inflammation. It is a simple, cheap and non-invasive test with high sensitivity and moderate specificity, which can be useful in the diagnosis and monitoring of inflammatory bowel disease (IBD). FC levels correlate well with bowel inflammation (both macroscopic and histological activity) and are not influenced by disease location or type of IBD. Despite the shortcoming with regards to specificity, it is the high sensitivity of FC that makes it a valuable screening tool in the diagnosis of IBD. It is especially effective in identifying children with low probability of IBD who would not benefit from further investigations. The cut-off value selected has a significant impact on the diagnostic accuracy of the test, influencing its sensitivity and specificity, and must be interpreted judiciously. Its role in disease monitoring is as an add-on test to Paediatric Ulcerative Colitis Activity Index and Paediatric Crohn's Disease Activity Index scores and can be used to differentiate disease relapse from functional symptoms. High levels of FC are also seen in a number of other conditions, such as gastrointestinal infections and coeliac disease. It is recommended that infective causes affecting the gut must be excluded first, before FC is measured. PMID- 26848105 TI - The value of mentorship in medical education. AB - BACKGROUND: The transition from senior medical student to working safely and effectively as a new junior doctor is one of the biggest challenges that a new graduate will face. In 2014 the General Medical Council published The state of medical education and practice in the UK, reporting that some new doctors continue to struggle with increased responsibilities. We classify these instances as a 'performance gap', describing occasions in clinical practice where an individual exceeds their performance capacity. The Medical Mentorship Programme addressed identified performance gaps through a structured curriculum of simulation-based education and facilitated clinical practice. METHODS: Programme content was based on the experiences of the authors and their peers in graduating from their undergraduate training programme and becoming junior doctors. A questionnaire was disseminated to junior doctors in their first clinical rotation. The questionnaire asked doctors to describe instances where they experienced a performance gap. These data informed the development of the Medical Mentorship Programme. The effect of this programme was then evaluated via focus group discussion. RESULTS: The Medical Mentorship Programme has been shown to be an effective conduit for supporting the transfer of learning needed to address performance gaps in students. The programme increased the confidence of students in preparation for clinical practice and allowed junior doctors to reflect on their professional development. The programme combined complementary teaching techniques - mentorship, simulation and direct clinical experience - to aid the professional development of both students and mentors. Some new doctors continue to struggle with increased responsibilities. PMID- 26848104 TI - The effects of Lycii Radicis Cortex on RANKL-induced osteoclast differentiation and activation in RAW 264.7 cells. AB - Post-menopausal osteoporosis is a serious age-related disease. After the menopause, estrogen deficiency is common, and excessive osteoclast activity causes osteoporosis. Osteoclasts are multinucleated cells generated from the differentiation of monocyte/macrophage precursor cells such as RAW 264.7 cells. The water extract of Lycii Radicis Cortex (LRC) is made from the dried root bark of Lycium chinense Mill. and is termed 'Jigolpi' in Korea. Its effects on osteoclastogenesis and post-menopausal osteoporosis had not previously been tested. In the present study, the effect of LRC on receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-induced osteoclast differentiation was demonstrated using a tartrate-resistant acid phosphatase (TRAP) assay and pit formation assay. Moreover, in order to analyze molecular mechanisms, we studied osteoclastogenesis-related markers such as nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, receptor activator of NF-kappaB (RANK), TRAP, cathepsin K (CTK), matrix metallopeptidase-9 (MMP-9), calcitonin receptor (CTR) and carbonic anhydrase II (CAII) using RT-qPCR and western blot analysis. Additionally, we also determined the effect of LRC on an ovariectomized (OVX) rat model. We noted that LRC inhibited RANKL-induced osteoclast differentiation via suppressing osteoclastogenesis-related markers. It also inhibited osteoporosis in the OVX rat model by decreasing loss of bone density and trabecular area. These results suggest that LRC exerts a positive effect on menopausal osteoporosis. PMID- 26848106 TI - Coaxial electrospun fibers: applications in drug delivery and tissue engineering. AB - Coelectrospinning and emulsion electrospinning are two main methods for preparing core-sheath electrospun nanofibers in a cost-effective and efficient manner. Here, physical phenomena and the effects of solution and processing parameters on the coaxial fibers are introduced. Coaxial fibers with specific drugs encapsulated in the core can exhibit a sustained and controlled release. Their exhibited high surface area and three-dimensional nanofibrous network allows the electrospun fibers to resemble native extracellular matrices. These features of the nanofibers show that they have great potential in drug delivery and tissue engineering applications. Proteins, growth factors, antibiotics, and many other agents have been successfully encapsulated into coaxial fibers for drug delivery. A main advantage of the core-sheath design is that after the process of electrospinning and release, these drugs remain bioactive due to the protection of the sheath. Applications of coaxial fibers as scaffolds for tissue engineering include bone, cartilage, cardiac tissue, skin, blood vessels and nervous tissue, among others. A synopsis of novel coaxial electrospun fibers, discussing their applications in drug delivery and tissue engineering, is covered pertaining to proteins, growth factors, antibiotics, and other drugs and applications in the fields of bone, cartilage, cardiac, skin, blood vessel, and nervous tissue engineering, respectively. WIREs Nanomed Nanobiotechnol 2016, 8:654-677. doi: 10.1002/wnan.1391 For further resources related to this article, please visit the WIREs website. PMID- 26848107 TI - Elucidation of the mTOR Pathway and Therapeutic Applications in Dermatology. AB - The member of the phosphatidylinositol 3-kinase family, mammalian target of rapamycin, is involved in modulating inflammatory response and regulating cellular processes associated with growth, differentiation, and angiogenesis. Recent years have seen major advances in our understanding of the mammalian target of rapamycin signaling pathway and the implication of this pathway in multiple genetic and inflammatory diseases and tumors. The development of the mammalian target of rapamycin inhibitors has given rise to new treatment approaches that have led to substantially improved outcomes in many diseases. In this article, we review the role of the mammalian target of rapamycin signaling pathway in the different skin diseases with which it has been associated, examine the therapeutic applications of drugs targeting this pathway, and provide an overview of current trends and future directions in research. PMID- 26848108 TI - Design and optimization of tricyclic gamma-secretase modulators. AB - Beginning with a diaminotriazine screening hit, several series of novel, tricyclic gamma-secretase modulators (GSMs) were designed. The SAR of several related series of GSMs is presented, and the in vivo profile of a lead molecule from the series is described. PMID- 26848109 TI - The natural flavone fukugetin as a mixed-type inhibitor for human tissue kallikreins. AB - The human tissue kallikreins (KLK1-KLK15) comprise a family of 15 serine peptidases detected in almost every tissue of the human body and that actively participate in many physiological and pathological events. Some kallikreins are involved in diseases for which no effective therapy is available, as for example, epithelial disorders, bacterial infections and in certain cancers metastatic processes. In recent years our group have made efforts to find inhibitors for all kallikreins, based on natural products and synthetic molecules, and all the inhibitors developed by our group presented a competitive mechanism of inhibition. Here we describe fukugetin, a natural product that presents a mixed type mechanism of inhibition against KLK1 and KLK2. This type of inhibitor is gaining importance today, especially for the development of exosite-type inhibitors, which present potential to selectively inhibit the enzyme activity only against specific substrate. PMID- 26848110 TI - New antibacterial isocoumarin glycosides from a wetland soil derived fungal strain Metarhizium anisopliae. AB - Eight new isocoumarin glycosides (1-8) were obtained from the solid culture of the wetland soil-derived fungus Metarhizium anisopliae (No. DTH12-10). Their chemical structures were elucidated by analyses of HR ESI-TOF MS, (1)H, (13)C NMR, (1)H-(1)H COSY, HSQC, and HMBC spectra. The absolute configurations were determined by single crystal X-ray diffraction, circular dichroism (CD) spectrum, and chemical derivatization methods. In addition, inhibition of the biofilm formation and the secretion of virulence factor of the new isocoumarin glycosides against Pseudomonas aeruginosa strain PAOA (clinical isolates) were evaluated. The result revealed that compound 1 showed antibacterial activity comparable with (Z)-4-bromo-5-(bromomethylene)-2(5H)-furanone (BF). PMID- 26848112 TI - Congenital heterotopic gastrointestinal cyst of the oral cavity: report of rare case. PMID- 26848111 TI - Hesperetin derivatives: Synthesis and anti-inflammatory activity. AB - Sixteen novel hesperetin derivatives containing Mannich base moiety were designed and synthesized and their anti-inflammatory activities were evaluated by inhibiting tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in mouse RAW264.7 macrophages. Compounds 3a-3k showed better hydrophilic, while compounds 3l-3p with aromatic groups was hydrophobic. The anti-inflammatory activity of title compounds was correlated with logP values, among them, compounds 3c, 3e and 3i with minus logP values exhibited best anti-inflammatory activity through decreasing both IL-6 and TNF-alpha. Furthermore, the expression of LPS-induced notch1 and inos was reduced by compounds 3c, 3e, and 3i, and compound 3e attenuated LPS-induced inos protein levels in a dose-dependent manner. PMID- 26848113 TI - Social network analysis provides insights into African swine fever epidemiology. AB - Pig movements play a significant role in the spread of economically important infectious diseases such as the African swine fever. Characterization of movement networks between pig farms and through other types of farm and household enterprises that are involved in pig value chains can provide useful information on the role that different participants in the networks play in pathogen transmission. Analysis of social networks that underpin these pig movements can reveal pathways that are important in the transmission of disease, trade in commodities, the dissemination of information and the influence of behavioural norms. We assessed pig movements among pig keeping households within West Kenya and East Uganda and across the shared Kenya-Uganda border in the study region, to gain insight into within-country and trans-boundary pig movements. Villages were sampled using a randomized cluster design. Data were collected through interviews in 2012 and 2013 from 683 smallholder pig-keeping households in 34 villages. NodeXL software was used to describe pig movement networks at village level. The pig movement and trade networks were localized and based on close social networks involving family ties, friendships and relationships with neighbours. Pig movement network modularity ranged from 0.2 to 0.5 and exhibited good community structure within the network implying an easy flow of knowledge and adoption of new attitudes and beliefs, but also promoting an enhanced rate of disease transmission. The average path length of 5 defined using NodeXL, indicated that disease could easily reach every node in a cluster. Cross-border boar service between Uganda and Kenya was also recorded. Unmonitored trade in both directions was prevalent. While most pig transactions in the absence of disease, were at a small scale (<5km) and characterized by regular agistment, most pig sales during ASF outbreaks were to traders or other farmers from outside the sellers' village at a range of >10km. The close social relationships between actors in pig movement networks indicate the potential for possible interventions to develop shared norms and mutually accepted protocols amongst smallholder pig keepers to better manage the risk of ASF introduction and transmission. PMID- 26848114 TI - Effects of meteorological factors and the lunar cycle on onset of parturition in cows. AB - The present paper summarizes a comprehensive retrospective study that was undertaken to investigate effects of meteorological factors and lunar cycle on gestation length and daily birth rate in cows. To this end, all cattle births in Switzerland between 2008 and 2010 (n=2,091,159) were related to detailed matched weather recordings. The study revealed some statistically significant effects of climate (temperature, barometric pressure, relative humidity) and weather (thunderstorms, heat index) on gestational length. Thunderstorms on the day before birth reduced the gestation length by 0.5 days. An increase in the birth rate was correlated with the temperature on the day before birth and the barometric pressure 3 days before birth. Differences in the barometric pressure >15hPa increased the birth rate by 4%. Nevertheless, the effects were not consistent and the modeled size of effect was so small that a clinical implication is unlikely. Although the daily birth rate was unevenly distributed across the lunar cycle, no clear pattern could be identified. Compared to the mean birth rate across the lunar cycle the highest daily birth rate was detected on day 4 after new moon (+1.9%) and the lowest on day 20 (-2.1%). PMID- 26848115 TI - Transmission of foot and mouth disease at the wildlife/livestock interface of the Kruger National Park, South Africa: Can the risk be mitigated? AB - In Southern Africa, the African buffalo (Syncerus caffer) is the natural reservoir of foot and mouth disease (FMD). Contacts between this species and cattle are responsible for most of the FMD outbreaks in cattle at the edge of protected areas, which generate huge economic losses. During the late 1980's and 90's, the erection of veterinary cordon fences and the regular vaccination of cattle exposed to buffalo contact at the interface of the Kruger National Park (KNP), proved to be efficient to control and prevent FMD outbreaks in South Africa. However, since 2000, the efficiency of those measures has deteriorated, resulting in an increased rate of FMD outbreaks in cattle outside KNP, currently occurring more than once a year. Based on retrospective ecological and epidemiological data, we developed a stochastic quantitative model to assess the annual risk of FMD virus (FMDV) transmission from buffalo to cattle herds present at the KNP interface. The model suggests that good immunization of approximately 75% of the cattle population combined with a reduction of buffalo/cattle contacts is an efficient combination to reduce FMDV transmission to one infective event every 5.5 years, emulating the epidemiological situation observed at the end of the 20th century, before current failure of control measures. The model also indicates that an increasing number of buffalo present in the KNP and crossing its boundaries, combined with a reduction in the vaccination coverage of cattle herds at the interface, increases 3-fold the risk of transmission (one infective event per year).The model proposed makes biological sense and provides a good representation of current knowledge of FMD ecology and epidemiology in Southern Africa which can be used to discuss with stakeholders on different management options to control FMD at the wildlife livestock interface and updated if new information becomes available. It also suggests that the control of FMD at the KNP interface is becoming increasingly challenging and will probably require alternative approaches to control this disease and its economic impact. PMID- 26848116 TI - Lineage-specific chimerism monitoring after allogeneic haematopoietic stem cell transplantation: do we really know what we are measuring? PMID- 26848117 TI - Bed-sharing by breastfeeding mothers: who bed-shares and what is the relationship with breastfeeding duration? AB - AIM: To explore the link between breastfeeding duration and bed-sharing frequency among women reporting a prenatal intention to breastfeed. METHODS: About 870 participants in a randomised breastfeeding trial, recruited at mid-pregnancy, provided weekly snapshots of breastfeeding and bed-sharing behaviour for 26 weeks following birth. Strength of prenatal breastfeeding intent was recorded at recruitment using Likert-type scales. RESULTS: Outcomes were frequency of bed sharing at home for at least one hour per week, and time to cessation of breastfeeding. There were insufficient data to classify bed-sharing pattern in 192/870 (22%) of mothers. Of the remainder, 44% (299/678) of participants 'rarely' or 'never' bed-shared, 28% (192/678) did so 'intermittently' and 28% (187/678) did so 'often'. These three groups did not differ significantly in marital status, income, infant gestational age, maternal age or delivery mode. Significantly, more participants who bed-shared 'often' reported strong prenatal breastfeeding intent (70% vs. 57% and 56% for 'intermittent' and 'rare' bed-share groups) and attached high prenatal importance to breastfeeding (95% vs. 87% and 82%). Significantly, more women who bed-shared frequently were breastfeeding at 6 months (p < 0.0001) than those who intermittently or rarely/never bed-shared. CONCLUSION: Women with strong motivation to breastfeed frequently bed-share. Given the complex relationship between bed-sharing and sudden infant death syndrome (SIDS) appropriate guidance balancing risk minimisation with support for breastfeeding mothers is crucial. PMID- 26848118 TI - Differential age susceptibility to influenza B/Victoria lineage viruses in the 2015 Australian influenza season. AB - Influenza B viruses make up an important part of the burden from seasonal influenza globally. The 2015 season in Australia saw an unusual predominance of influenza B with a distinctive switch during the season from B/Yamagata/16/88 lineage viruses to B/Victoria/2/87 lineage viruses. We also noted significant differences in the age groups infected by the different B lineages, with B/Victoria infecting a younger population than B/Yamagata, that could not be explained by potential prior exposure. PMID- 26848119 TI - Granulocyte colony-stimulating factor (G-CSF) plays an important role in immune complex-mediated arthritis. AB - Neutrophils are an abundant cell type in many chronic inflammatory diseases such as rheumatoid arthritis (RA); however, their contribution to the pathology of RA has not been widely studied. A key cytokine involved in neutrophil development and function is granulocyte-colony stimulating factor (G-CSF). In this study we used the K/BxN serum-transfer arthritis (STA) model, mimicking the effector phase of RA, to investigate the importance of G-CSF in arthritis development and its relation to neutrophils. Here, we show for the first time in this model that G CSF levels are increased both in the serum and in inflamed paws of arthritic mice and importantly that G-CSF blockade leads to a profound reduction in arthritis severity, as well as reduced numbers of neutrophils in blood. Moreover, CXCL1 and CXCL2 levels in the arthritic joints were also lowered. Our data demonstrate that G-CSF is a pivotal driver of the disease progression in the K/BxN STA model and possibly acts in part by regulating neutrophil numbers in the circulation. Therefore, our findings suggest that G-CSF might be a suitable target in RA, and perhaps in other immune complex-driven pathologies. PMID- 26848120 TI - Genomic and proteomic profiling for cancer diagnosis in dogs. AB - Global gene expression, whereby tumours are classified according to similar gene expression patterns or 'signatures' regardless of cell morphology or tissue characteristics, is being increasingly used in both the human and veterinary fields to assist in cancer diagnosis and prognosis. Many studies on canine tumours have focussed on RNA expression using techniques such as microarrays or next generation sequencing. However, proteomic studies combining two-dimensional polyacrylamide gel electrophoresis or two-dimensional differential gel electrophoresis with mass spectrometry have also provided a wealth of data on gene expression in tumour tissues. In addition, proteomics has been instrumental in the search for tumour biomarkers in blood and other body fluids. PMID- 26848121 TI - Corrigendum: Systematic pan-cancer analysis of tumour purity. PMID- 26848122 TI - The genetic assessment of looked after children: common reasons for referral and recent advances. AB - Looked after children are recognised as generally having greater health needs than their peers. There are numerous potential causes, environmental and genetic, and the aetiology is often multifactorial. Assessments, especially clinical genetic ones, may be limited if the information available is incomplete or not shared. There have been some exciting recent advances in diagnostic genetic testing and more are on the horizon. However, we are currently only able to make a genetic diagnosis in less than half of patients, even when both parents are available for comparative testing. There may, therefore, remain an inevitable degree of residual uncertainty about the genetic contribution to a particular child's problems. There are increasing societal pressures for genetic information to be made available to individuals in general. However, there are significant considerations in carrier/predictive testing in children and we would maintain that looked after children should not be treated differently to other children in this regard, unless there is a compelling 'best interest' justification for so doing. Diagnostic criteria exist for fetal alcohol syndrome and other embryopathies and should be applied. Such should be considered as diagnoses of exclusion, so a child should not be prematurely labelled with these conditions, without fully assessing for the contribution of other factors, genetic or otherwise. PMID- 26848125 TI - Need to consider non-randomised evidence to assess the effectiveness and safety of interventions promoting maternal awareness of decreased fetal movements. PMID- 26848123 TI - Increasing Neuroplasticity to Bolster Chronic Pain Treatment: A Role for Intermittent Fasting and Glucose Administration? AB - Neuroplastic changes in brain structure and function are not only a consequence of chronic pain but are involved in the maintenance of pain symptoms. Thus, promotion of adaptive, treatment-responsive neuroplasticity represents a promising clinical target. Emerging evidence about the human brain's response to an array of behavioral and environmental interventions may assist in identifying targets to facilitate increased neurobiological receptivity, promoting healthy neuroplastic changes. Specifically, strategies to maximize neuroplastic responsiveness to chronic pain treatment could enhance treatment gains by optimization of learning and positive central nervous system adaptation. Periods of heightened plasticity have been traditionally identified with the early years of development. More recent research, however, has identified a wide spectrum of methods that can be used to "reopen" and enhance plasticity and learning in adults. In addition to transcranial direct current stimulation and transcranial magnetic stimulation, behavioral and pharmacological interventions have been investigated. Intermittent fasting and glucose administration are two propitious strategies, that are noninvasive, inexpensive to administer, implementable in numerous settings, and might be applicable across differing chronic pain treatments. Key findings and neurophysiological mechanisms are summarized, and evidence for the potential clinical contributions of these two strategies toward ameliorating chronic pain is presented. PERSPECTIVE: Neuroplastic changes are a defining feature of chronic pain and a complicating factor in treatment. Noninvasive strategies to optimize the brain's response to treatment interventions might improve learning and memory, increase the positive adaptability of the central nervous system, and enhance treatment outcomes. PMID- 26848124 TI - Chromosome-scale shotgun assembly using an in vitro method for long-range linkage. AB - Long-range and highly accurate de novo assembly from short-read data is one of the most pressing challenges in genomics. Recently, it has been shown that read pairs generated by proximity ligation of DNA in chromatin of living tissue can address this problem, dramatically increasing the scaffold contiguity of assemblies. Here, we describe a simpler approach ("Chicago") based on in vitro reconstituted chromatin. We generated two Chicago data sets with human DNA and developed a statistical model and a new software pipeline ("HiRise") that can identify poor quality joins and produce accurate, long-range sequence scaffolds. We used these to construct a highly accurate de novo assembly and scaffolding of a human genome with scaffold N50 of 20 Mbp. We also demonstrated the utility of Chicago for improving existing assemblies by reassembling and scaffolding the genome of the American alligator. With a single library and one lane of Illumina HiSeq sequencing, we increased the scaffold N50 of the American alligator from 508 kbp to 10 Mbp. PMID- 26848126 TI - Cryopyrin-associated periodic fever syndrome manifesting as Tolosa-Hunt syndrome. AB - BACKGROUND: Tolosa-Hunt syndrome (THS) is characterized by unilateral orbital pain, ipsilateral oculomotor paresis and a prompt response to treatment with corticosteroids. Several reports have demonstrated that the clinical features of THS are not specific to one causal aetiology and can lead to misdiagnosis. CASE REPORT: We report the case of a patient diagnosed with THS after an episode of unilateral orbital pain and diplopia with demonstration of granulomatous inflammation of both cavernous sinus on cerebral magnetic resonance imaging and an immediate response to treatment with corticosteroids. Progression of the disease over the following years, accompanied by increasing signs of inflammation on cerebral magnetic resonance imaging and cerebrospinal fluid pleocytosis, led to further diagnostic tests. Genetic analyses revealed a heterozygote low penetrance mutation (Q703K) of the cryopyrin/NLRP3 gene compatible with a cryopyrin-associated periodic fever syndrome. DISCUSSION: This case report demonstrates that THS can be a central nervous system manifestation of cryopyrin associated periodic fever syndrome, which therefore represents a differential diagnosis of THS, even in elderly patients. PMID- 26848127 TI - Pseudomigraine with transient neurological deficits and cerebrospinal fluid lymphocytosis or HaNDL syndrome: A case report with confusion and positive IgM antibodies to CMV in serum. PMID- 26848129 TI - Recapitulation and Synthesis: Proliferation of Meta-Analysis in Structural Interventional Cardiology. PMID- 26848128 TI - Twenty years of triptans in the United States Medicaid programs: Utilization and reimbursement trends from 1993 to 2013. AB - OBJECTIVE: After sumatriptan was approved by the Food and Drug Administration in 1992, triptans became first-line anti-migraine therapies. Rapidly rising triptan expenditures, however, led payers, including Medicaid, to implement cost containment policies. We describe triptan utilization and reimbursement trends in Medicaid. METHODS: Using national summary files for outpatient drug utilization, utilization and expenditure data from 1993 to 2013 were extracted and summed for all triptan national drug codes reimbursed by Medicaid. Data were collected separately for tablets, injections and sprays. RESULTS: The number of triptan prescriptions increased from 87,348 in 1993 to 0.9 million in 2004; fell to 0.4 million in 2009; rose to 1 million in 2011; and rose 1.2 million in 2013. In 2013, Medicaid spent $96.8 million on triptans: 74.4%, 18.4% and 7.2% for tablets, injections and sprays, respectively. Average reimbursement per prescription was $54 for tablets, $351 for injections and $235 for sprays in 2013. From 1993 to 2013, sumatriptan was the most widely prescribed among the triptans. CONCLUSIONS: The substantial increase in triptan prescriptions from 2009 to 2011, without being convincingly explained by either rising migraine prevalence or rising Medicaid enrollment, is suggestive of reduced access to these medications prior to 2009. Cost-containment policies may have inadvertently prevented Medicaid migraineurs from obtaining appropriate pharmacotherapy. PRIOR PRESENTATIONS: An earlier version of this paper was presented as a poster at the Annual Meeting of the International Society for Pharmacoeconomics and Outcomes Research, Philadelphia, PA, May 2015, where it received a finalist award. PMID- 26848130 TI - Are topical antibiotics an alternative to oral antibiotics for children with acute otitis media and ear discharge? PMID- 26848131 TI - Midterm Patency After Femoropopliteal Interventions: A Comparison of Standard and Interwoven Nitinol Stents and Drug-Coated Balloons in a Single-Center, Propensity Score-Matched Analysis. AB - PURPOSE: To describe and compare primary patency rates in patients undergoing endovascular femoropopliteal interventions with standard or interwoven nitinol stents or drug-coated balloons. METHODS: A cohort of 1292 patients was treated for symptomatic femoropopliteal occlusive disease classified as Rutherford category >= 1 at a large vascular center between June 2006 and August 2013 using either standard nitinol stents (SNS; n=432), interwoven nitinol stents (INS; n=470), or drug-coated balloons (DCB; n=390). Primary patency rates were assessed by ultrasound or angiographic readings for over 3 years of follow-up. Propensity score-matched pairs were formed to compare each treatment with another using survival analysis. RESULTS: Survival curves of primary patency favored INS compared with SNS in 368 propensity score-matched pairs (p<0.001). Kaplan-Meier estimates at 1, 2, and 3 years were 86.6%, 76.4%, and 68.9%, respectively, in the INS group vs 60.5%, 46.1%, and 42.1%, respectively, in the SNS group. No significant difference (p=0.232) was seen for the comparison of SNS vs DCB in 284 matched pairs over long-term follow-up (primary patency estimates at 1, 2, and 3 years were 79.8%, 53.8%, and 32.9%, respectively, in the DCB group vs 60.5%, 44.8%, and 40.3%, respectively, in the SNS group). Survival curves of primary patency favored INS over DCB in 254 matched pairs (p<0.001). Kaplan-Meier estimates at 1, 2, and 3 years were 79.0%, 51.2%, and 30.1%, respectively, in the DCB group vs 89.0%, 76.9%, and 66.2%, respectively, in the INS group. CONCLUSION: Propensity score-based analysis of primary patency suggests profound differences in restenosis rates between various treatment modalities for femoropopliteal disease for over 3 years of follow-up. PMID- 26848132 TI - Combined Radial-Pedal Access Strategy and Radial-Pedal Rendezvous in the Revascularization of Complex Total Occlusions of the Superficial Femoral Artery (the "No Femoral Access" Strategy). AB - PURPOSE: To describe the combined use of radial-pedal access for recanalization of complex superficial femoral artery (SFA) occlusions unsuitable for transfemoral recanalization. TECHNIQUE: Patients are selected for this strategy if they have a long (>= 10 cm) SFA occlusion with unfavorable aortoiliac anatomy, an absent ostial stump, or severely diseased and calcified distal reconstitution. Left radial artery and distal anterior or posterior tibial artery are accessed with 6-F and 4-F sheaths, respectively. The SFA lesion is crossed retrogradely with a 0.035-inch wire system. If retrograde crossing is not immediately successful, transradial subintimal tracking and radial-pedal subintimal rendezvous are used to allow retrograde reentry. Fifteen patients (mean age 62 +/ 5 years; 11 men) have been treated in this fashion, and frequently stented, through the tibiopedal access. Seven patients required radial-pedal rendezvous to facilitate retrograde reentry. Two patients underwent transradial iliac stenting during the same session, and 1 patient underwent transradial kissing angioplasty of the profunda. No major complication occurred in any patient. After the procedure, the pulse across the accessed tibial artery was palpable in all patients. CONCLUSION: In patients with long and complex SFA occlusion unsuitable for transfemoral recanalization, a radial-pedal strategy can overcome revascularization obstacles. PMID- 26848133 TI - Quadruple Vessel Coronary Artery Bypass Grafting in a 14-Year-Old Child With Plasminogen Activator Inhibitor-1 4G/4G Gene Polymorphism. AB - Myocardial ischemia due to coronary artery disease is an extremely rare condition in childhood and adolescence. Absence of obvious serious risk factors remains a challenge to modern cardiology. We present the case of a 14-year-old boy who underwent quadruple-vessel coronary artery bypass grafting with bilateral pedicled internal mammary artery and bilateral radial artery grafting. We try to highlight a rare but important 4G variant PAI-1 (SERPINE 1) gene mutation as the etiology of severe coronary artery disease in our patient. To the best of our knowledge, he is one of the youngest patients who underwent coronary artery bypass surgery with 4 arterial grafts. PMID- 26848134 TI - Pacemaker battery scandal. PMID- 26848135 TI - Infrared PINEM developed by diffraction in 4D UEM. AB - The development of four-dimensional ultrafast electron microscopy (4D UEM) has enabled not only observations of the ultrafast dynamics of photon-matter interactions at the atomic scale with ultrafast resolution in image, diffraction, and energy space, but photon-electron interactions in the field of nanoplasmonics and nanophotonics also have been captured by the related technique of photon induced near-field electron microscopy (PINEM) in image and energy space. Here we report a further extension in the ongoing development of PINEM using a focused, nanometer-scale, electron beam in diffraction space for measurements of infrared light-induced PINEM. The energy resolution in diffraction mode is unprecedented, reaching 0.63 eV under the 200-keV electron beam illumination, and separated peaks of the PINEM electron-energy spectrum induced by infrared light of wavelength 1,038 nm (photon energy 1.2 eV) have been well resolved for the first time, to our knowledge. In a comparison with excitation by green (519-nm) pulses, similar first-order PINEM peak amplitudes were obtained for optical fluence differing by a factor of more than 60 at the interface of copper metal and vacuum. Under high fluence, the nonlinear regime of IR PINEM was observed, and its spatial dependence was studied. In combination with PINEM temporal gating and low-fluence infrared excitation, the PINEM diffraction method paves the way for studies of structural dynamics in reciprocal space and energy space with high temporal resolution. PMID- 26848136 TI - On the relationship between aerosol model uncertainty and radiative forcing uncertainty. AB - The largest uncertainty in the historical radiative forcing of climate is caused by the interaction of aerosols with clouds. Historical forcing is not a directly measurable quantity, so reliable assessments depend on the development of global models of aerosols and clouds that are well constrained by observations. However, there has been no systematic assessment of how reduction in the uncertainty of global aerosol models will feed through to the uncertainty in the predicted forcing. We use a global model perturbed parameter ensemble to show that tight observational constraint of aerosol concentrations in the model has a relatively small effect on the aerosol-related uncertainty in the calculated forcing between preindustrial and present-day periods. One factor is the low sensitivity of present-day aerosol to natural emissions that determine the preindustrial aerosol state. However, the major cause of the weak constraint is that the full uncertainty space of the model generates a large number of model variants that are equally acceptable compared to present-day aerosol observations. The narrow range of aerosol concentrations in the observationally constrained model gives the impression of low aerosol model uncertainty. However, these multiple "equifinal" models predict a wide range of forcings. To make progress, we need to develop a much deeper understanding of model uncertainty and ways to use observations to constrain it. Equifinality in the aerosol model means that tuning of a small number of model processes to achieve model-observation agreement could give a misleading impression of model robustness. PMID- 26848138 TI - Novel Use of Google Glass for Procedural Wireless Vital Sign Monitoring. AB - Purpose This study investigates the feasibility and potential utility of head mounted displays for real-time wireless vital sign monitoring during surgical procedures. Methods In this randomized controlled pilot study, surgery residents (n = 14) performed simulated bedside procedures with traditional vital sign monitors and were randomized to addition of vital sign streaming to Google Glass. Time to recognition of preprogrammed vital sign deterioration and frequency of traditional monitor use was recorded. User feedback was collected by electronic survey. Results The experimental group spent 90% less time looking away from the procedural field to view traditional monitors during bronchoscopy (P = .003), and recognized critical desaturation 8.8 seconds earlier; the experimental group spent 71% (P = .01) less time looking away from the procedural field during thoracostomy, and recognized hypotension 10.5 seconds earlier. Trends toward earlier recognition of deterioration did not reach statistical significance. The majority of participants agreed that Google Glass increases situational awareness (64%), is helpful in monitoring vitals (86%), is easy to use (93%), and has potential to improve patient safety (85%). Conclusion In this early feasibility study, use of streaming to Google Glass significantly decreased time looking away from procedural fields and resulted in a nonsignificant trend toward earlier recognition of vital sign deterioration. Vital sign streaming with Google Glass or similar platforms is feasible and may enhance procedural situational awareness. PMID- 26848137 TI - Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results. AB - Elevated apoC-III levels predict increased cardiovascular risk when present on LDL and HDL particles. We developed novel high-throughput chemiluminescent ELISAs that capture apoB, lipoprotein (a) [Lp(a)], and apoA-I in plasma and then detect apoC-III on these individual lipoproteins as apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoAI complexes, respectively. We assessed the effects on these complexes of placebo or 100-300 mg volanesorsen, a generation 2.0+ antisense drug that targets apoC3 mRNA in patients with hypertriglyceridemia, including familial chylomicronemia syndrome (n = 3), volanesorsen monotherapy (n = 51), and as add on to fibrate (n = 26), treated for 85 days and followed for 176 days. Compared with placebo, volanesorsen was associated with an 82.3 +/- 11.7%, 81.3 +/- 15.7%, and 80.8 +/- 13.6% reduction in apoCIII-apoB, apoCIII-Lp(a), and apoCIII-apoA-I, respectively (300 mg dose;P< 0.001 for all), at day 92. Strong correlations in all assay measures were noted with total plasma apoC-III, chylomicron-apoC-III, and VLDL-apoC-III. In conclusion, novel high-throughput ELISAs were developed to detect lipoprotein-associated apoC-III, including for the first time on Lp(a). Volanesorsen uniformly lowers apoC-III on apoB-100, Lp(a), and apoA-I lipoproteins, and may be a potent agent to reduce triglycerides and cardiovascular risk mediated by apoC-III. PMID- 26848139 TI - Possible Involvement of Nitric Oxide Modulatory Mechanisms in the Neuroprotective Effect of Centella asiatica Against Sleep Deprivation Induced Anxiety Like Behaviour, Oxidative Damage and Neuroinflammation. AB - Sleep deprivation (SD) is an experience of inadequate or poor quality of sleep that may produce significant alterations in multiple neural systems. Centella asiatica (CA) is a psychoactive medicinal herb with immense therapeutic potential. The present study was designed to explore the possible nitric oxide (NO) modulatory mechanism in the neuroprotective effect of CA against SD induced anxiety like behaviour, oxidative damage and neuroinflammation. Male laca mice were sleep deprived for 72 h, and CA (150 and 300 mg/kg) was administered alone and in combination with NO modulators for 8 days, starting five days before 72-h SD exposure. Various behavioural (locomotor activity, elevated plus maze) and biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels and superoxide dismutase activity), neuroinflammation marker (TNF-alpha) were assessed subsequently. CA (150 and 300 mg/kg) treatment for 8 days significantly improved locomotor activity, anti-anxiety like effect and attenuated oxidative damage and TNF alpha level as compared to sleep-deprived 72-h group. Also while the neuroprotective effect of CA was increased by NO antagonists, it was diminished by NO agonists. The present study suggests that NO modulatory mechanism could be involved in the protective effect of CA against SD-induced anxiety-like behaviour, oxidative damage and neuroinflammation in mice. PMID- 26848140 TI - Medication Overuse Headache. AB - Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. In reply to a question about medication overuse headache, its presentation, causes, treatment, and prevention will be discussed. PMID- 26848141 TI - Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona. AB - INTRODUCTION: The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. MATERIAL AND METHODS: A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. RESULTS: A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. CONCLUSIONS: Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy. PMID- 26848142 TI - Dual time-point (18)F-FDG PET/CT to assess response to radiofrequency ablation of lung metastases. AB - AIM: To establish the usefulness of dual time-point PET/CT imaging in determining the response to radiofrequency ablation (RFA) of solitary lung metastases from gastrointestinal cancer. MATERIALS AND METHODS: This prospective study included 18 cases (3 female, 15 male, mean age 71+/-15 yrs) with solitary lung metastases from malignant digestive tract tumors candidates for RFA. PET/CT images 1h after injection of 4.07MBq/kg of (18)F-FDG (standard images) were performed at baseline, 1 month, and 3 months after RFA. PET/CT images 2h after injection centered in the thorax at 1 month after RFA were also performed (delayed images). A retention index (RI) of dual time-point images was calculated as follows: RI=(SUVmax delayed image-SUVmax standard image/SUVmax standard image)*100. Pathological confirmation of residual tumor by histology of the treated lesion was considered as local recurrence. A negative imaging follow-up was considered as complete response. RESULTS: Local recurrence was found in 6/18 lesions, and complete response in the remaining 12. The mean percentage change in SUVmax at 1 month and at 3 months showed a sensitivity and specificity for PET/CT of 50% and 33%, and 67% and 92%, respectively. The RI at 1 month after RFA showed a sensitivity and specificity of 83% and 92%, respectively. CONCLUSIONS: Dual time point PET/CT can predict the outcome at one month after RFA in lung metastases from digestive tract cancers. The RI can be used to indicate the need for further procedures to rule out persistent tumor due to incomplete RFA. PMID- 26848143 TI - Cluster of atypical adult Guillain-Barre syndrome temporally associated with neurological illness due to EV-D68 in children, South Wales, United Kingdom, October 2015 to January 2016. AB - We report a cluster of atypical Guillain-Barre syndrome in 10 adults temporally related to a cluster of four children with acute flaccid paralysis, over a 3 month period in South Wales, United Kingdom. All adult cases were male, aged between 24 and 77 years. Seven had prominent facial diplegia at onset. Available electrophysiological studies showed axonal involvement in five adults. Seven reported various forms of respiratory disease before onset of neurological symptoms. The ages of children ranged from one to 13 years, three of the four were two years old or younger. Enterovirus testing is available for three children; two had evidence of enterovirus D68 infection in stool or respiratory samples. We describe the clinical features, epidemiology and state of current investigations for these unusual clusters of illness. PMID- 26848144 TI - Radiation-Induced Breast Angiosarcoma: Case Report and Clinical Approach. AB - IMPORTANCE: Radiation-induced angiosarcoma after conservative treatment of breast cancer affects a small percentage of patients but has a significant impact on survival. Early detection requires a high index of suspicion and is important for optimal management of this aggressive disease. OBSERVATIONS: The patient reported here presented with radiation-induced angiosarcoma of the left breast 14 years after radiation therapy. Histopathology was positive for anti-CD31, anti-CD34, D2 40, and anti-factor VIII (von Willebrand). She underwent a total mastectomy and is still in remission 20 months later. The authors present a review of the clinical presentation, diagnostic methods, and treatment options. CONCLUSIONS: This case report demonstrates the importance of long-term follow-up and investigation of even the subtlest cutaneous changes in the breast after radiation treatment, because radiation-induced angiosarcoma is a very aggressive disease that could benefit from early diagnosis and management. PMID- 26848145 TI - Use of Apremilast in Combination With Other Therapies for Treatment of Chronic Plaque Psoriasis: A Retrospective Study. AB - BACKGROUND: Apremilast is an oral phosphodiesterase 4 inhibitor that has been approved as monotherapy for the treatment of moderate to severe chronic plaque psoriasis. No data exist on the safety or efficacy of apremilast as a component of combination therapy with either phototherapy or conventional systemic or biological therapies. OBJECTIVE: To evaluate the short term-efficacy and safety of apremilast in combination with at least one form of photo-, systemic, or biologic therapy in the treatment of chronic plaque psoriasis. METHODS: A retrospective chart review was conducted for patients who received apremilast in addition to systemic, biologic, or phototherapy. The primary outcome was the proportion of patients achieving at least 75% improvement in Psoriasis Area and Severity Index score (PASI-75). RESULTS: A total of 81 patients with plaque psoriasis were treated with apremilast in combination with at least 1 other therapy (NB-UVB, methotrexate, acitretin, cyclosporin, etanercept, adalimumab, infliximab, or ustekinumab). Fourteen patients (17%) discontinued treatment before completion of 12 weeks of apremilast therapy. Sixty-seven patients continued on drug past 12 weeks. Of these patients, 81% achieved PASI-75 at week 12 after apremilast was added to an existing therapy. Nausea and/or diarrhea were reported in 25% of these patients, and weight loss was observed in 15%. CONCLUSION: Apremilast can be safely and effectively combined with phototherapy, systemic, and/or biological agents in patients with plaque psoriasis not responding adequately to these agents alone. Gastrointestinal side effects were manageable in the majority of patients. PMID- 26848146 TI - Structural, Organizational, and Interpersonal Factors Influencing Interprofessional Collaboration on Sexual Assault Response Teams. AB - Sexual Assault Response Teams (SARTs) are multidisciplinary teams that coordinate multiple systems (e.g., medical, law enforcement, prosecutors, and rape crisis center advocates) to provide comprehensive care to victims and to collect high quality forensic evidence to facilitate investigation and prosecution. Relatively little guidance is provided about effective teamwork strategies in resources on forming SARTs. Using in-depth surveys with the SART coordinators and telephone surveys (including close-ended and open-ended questions) with 79 professionals involved in three active, formal SARTs in one state, this study examined structural, organizational, and interpersonal factors that influence interprofessional collaboration on SART. Study findings indicate that perceived structural factors and interpersonal factors were significantly associated with SART members'/responders' perceptions of the quality of interprofessional collaboration on their SART. Findings suggest that individuals' perceptions of professionalization and power disparities between professions pose challenges to perceived interprofessional collaboration on SART. Compared with criminal justice and medical professionals, victim advocacy rated the level of collaboration on their SART significantly lower. The overall picture from the data was that SART professionals perceived mutual respect, trust, and commitment to collaboration to be pervasive on their SARTs, even though recognition of professional conflicts was also prevalent, suggesting that professionals understood that interpersonal conflict was distinct from professional conflict. Initial SART trainings should address the benefits of the team response, professional roles, and communication and conflict resolution skills, and ongoing training should provide professionals the opportunity to raise positive and negative examples of their collaborative efforts to explore existing tensions and constraints on the team for conflict resolution. PMID- 26848147 TI - The Effect of Intimate Partner Violence on the Psychosocial Development of Toddlers. AB - This study used data from the National Survey of Child and Adolescent Well-Being II to examine the effects of intimate partner violence (IPV) on child-welfare involved toddlers' psychosocial development. The sample was limited to toddlers aged 12 to 18 months with mothers who did ( n = 102) and did not ( n = 163) report IPV physical victimization. Multiple linear regression analyses showed, when compared with mothers who did not report IPV physical victimization, mothers who reported IPV physical victimization were more likely to have toddlers with higher levels of socioemotional and behavioral problems ( B = 5.06, p < .001). Conversely, delayed social competence was not associated with IPV ( B = -1.33, p > .05). Further analyses examining only toddlers with mothers who reported IPV physical victimization revealed, when compared with IPV-exposed toddlers who had a child welfare report of physical abuse as the primary maltreatment type, those with IPV as the primary maltreatment type were at lower risk of having socioemotional and behavioral problems ( B = -12.90, p < .05) and delayed social competence ( B = 3.27, p < .05). These findings indicate a significant concern regarding toddler psychosocial development when a mother has experienced IPV. This concern is even greater among IPV-exposed toddlers who experience physical abuse. We recommend child welfare workers assess for IPV. Once identified, early prevention and intervention services should be offered and tailored to the specific needs of IPV-affected families. PMID- 26848148 TI - A head-to-head pharmacodynamic comparison of prasugrel vs. ticagrelor after switching from clopidogrel in patients with coronary artery disease: results of a prospective randomized study. AB - AIMS: Pharmacodynamic (PD) studies comparing prasugrel and ticagrelor have reached inconsistent findings. Therefore, a comprehensive investigation comparing the PD effects of prasugrel vs. ticagrelor after switching from clopidogrel therapy, exploring both loading dose (LD) and maintenance dose (MD) regimens represented the aim of this study. METHODS AND RESULTS: Patients (n = 110) with coronary artery disease were randomized to prasugrel (60 mg LD/10 mg MD q.d.) or ticagrelor (180 mg LD/90 mg MD b.i.d) therapy for 1 week. Pharmacodynamic assessments were conducted using three assays (vasodilator-stimulated phosphoprotein, VerifyNow P2Y12, and light transmittance aggregometry, LTA) at baseline, 30 min, 2, 24 h, and 1 week. The impact of initiating ticagrelor MD 12 vs. 24 h after LD administration was also assessed. Switching clopidogrel-treated patients to an LD of prasugrel or ticagrelor was associated with a reduction in platelet reactivity at 30 min and was sustained at all time points up to 1 week with the MD (P < 0.001 for all assays). Platelet reactivity was similar with prasugrel and ticagrelor with all assays at 30 min, 2 h, and 1 week (P > 0.05 for all time points), with the exception of LTA at 30 min (lower with prasugrel; P = 0.003). At 24 h, platelet reactivity was lower among patients initiating ticagrelor MD after 12 vs. 24 h post-LD. Rates of high platelet reactivity (HPR) were markedly reduced and similar between groups. CONCLUSION: Prasugrel and ticagrelor exert similar levels of P2Y12 inhibition achieving more potent PD effects and reduced HPR rates compared with clopidogrel which are reached promptly following LD and sustained with MD. CLINICALTRIALSGOV IDENTIFIER: NCT01852175. PMID- 26848149 TI - Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1. AB - Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic embolism. Today's clinician is faced with the difficult task of selecting a suitable OAC for a patient with a particular clinical profile or a particular pattern of risk factors and concomitant diseases. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. NOACs for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In the first of a two-part review, we discuss the choice of NOAC for stroke prevention in the following subgroups of patients with AF: (i) stable coronary artery disease or peripheral artery disease, including percutaneous coronary intervention with stenting and triple therapy; (ii) cardioversion, ablation and anti-arrhythmic drug therapy; (iii) mechanical valves and rheumatic valve disease, (iv) patients with time in therapeutic range of >70% on warfarin; (v) patients with a single stroke risk factor (CHA2DS2VASc score of 1 in males, 2 in females); and (vi) patients with a single first episode of paroxysmal AF. Although there are no major differences in terms of efficacy and safety between the NOACs for some clinical scenarios, in others we are able to suggest that particular drugs and/or doses be prioritized for anticoagulation. PMID- 26848150 TI - Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 2. AB - The choice of oral anticoagulant (OAC) for patients with atrial fibrillation (AF) may be influenced by individual clinical features or by patterns of risk factors and comorbidities. We reviewed analyses of subgroups of patients from trials of vitamin K antagonists vs. non-vitamin K oral anticoagulants (NOACs) for stroke prevention in AF with the aim to identify patient groups who might benefit from a particular OAC more than from another. In addition, we discuss the timing of initiation of anticoagulation. In the second of a two-part review, we discuss the use of NOAC for stroke prevention in the following subgroups of patients with AF: (vii) secondary stroke prevention in patients after stroke or transient ischaemic attack (TIA), (viii) patients with acute stroke requiring thrombolysis or thrombectomy, (ix) those initiating or restarting OAC treatment after stroke or TIA, (x) those with renal impairment on dialysis, (xi) the elderly, (xii) those at high risk of gastrointestinal bleeding, and (xiii) those with hypertension. In addition, we discuss adherence and compliance. Finally, we present a summary of treatment suggestions. In specific subgroups of patients with AF, evidence supports the use of particular NOACs and/or particular doses of anticoagulant. The appropriate choice of treatment for these subgroups will help to promote optimal clinical outcomes. PMID- 26848151 TI - Veliparib Alone or in Combination with Mitomycin C in Patients with Solid Tumors With Functional Deficiency in Homologous Recombination Repair. AB - BACKGROUND: BRCA germline mutations are being targeted for development of PARP inhibitors. BRCA genes collaborate with several others in the Fanconi Anemia (FA) pathway. We screened cancer patients' tumors for FA functional defects then aimed to establish the safety/feasibility of administering PARP inhibitors as monotherapy and combined with a DNA-breaking agent. METHODS: Patients underwent FA functional screening for the presence (or lack) of tumor FancD2 nuclear foci formation on their archival tumor material, utilizing a newly developed method (Fanconi Anemia triple-stain immunofluorescence [FATSI]), performed in a Clinical Laboratory Improvement Amendments-certified laboratory. FATSI-negative patients were selected for enrollment in a two-arm dose escalation trial of veliparib, or veliparib/mitomycin-C (MMC). RESULTS: One hundred eighty-five of 643 (28.7%) screened patients were FATSI-negative. Sixty-one received veliparib or veliparib/MMC through 14 dose levels. Moderate/severe toxicities included fatigue (DLT at veliparib 400mg BID), diarrhea, and thrombocytopenia. Recommended doses are 300mg BID veliparib and veliparib 200mg BID for 21 days following 10mg/m(2) MMC every 28 days. Six antitumor responses occurred, five in the combination arm (3 breast, 1 ovarian, 1 endometrial [uterine], and 1 non-small cell lung cancer). Two patients have received 36 and 60 cycles to date. BRCA germline analysis among 51 patients revealed five deleterious mutations while a targeted FA sequencing gene panel showed missense/nonsense mutations in 29 of 49 FATSI-negative tumor specimens. CONCLUSIONS: FATSI screening showed that a substantial number of patients' tumors have FA functional deficiency, which led to germline alterations in several patients' tumors. Veliparib alone or with MMC was safely administered to these patients and produced clinical benefit in some. However, a better understanding of resistance mechanisms in this setting is needed. PMID- 26848152 TI - Anomalous origin of the coronary artery arising from the opposite sinus: prevalence and outcomes in patients undergoing coronary CTA. AB - AIMS: The impact of coronary computed tomographic angiography (CTA) on management of anomalous origin of the coronary artery arising from the opposite sinus (ACAOS) remains uncertain. We examined the prevalence, anatomical characterization, and outcomes of ACAOS patients undergoing CTA. METHODS AND RESULTS: Among 5991 patients referred for CTA at two tertiary hospitals between January 2004 and June 2014, we identified 103 patients (1.7% prevalence) with 110 ACAOS vessels. Mean age was 52 years (range 5-83, 63% male), with 55% previously known ACAOS and 45% discovered on CTA. ACAOS subtypes included: 39% interarterial (n = 40 anomalous right coronary artery, n = 3 anomalous left coronary artery), 38% retroaortic, 15% subpulmonic, 5% prepulmonic, and 2% other. ACAOS patients were assessed for symptoms, ischaemic test results, revascularization, all-cause or cardiovascular (CV) death, and myocardial infarction. CTAs were reviewed for ACAOS course, take-off height and angle, length and severity of proximal narrowing, intramural course, and obstructive coronary artery disease (CAD). In follow-up (median 5.8 years), there were 20 surgical revascularizations and 3 CV deaths. After adjusting for obstructive CAD (n = 21/103, 20%), variables associated with ACAOS revascularization included the following: CV symptoms, proximal vessel narrowing >=50%, length of narrowing >5.4 mm, and an interarterial course. CONCLUSION: The prevalence of ACAOS on CTA was 1.7%, including 45% of cases discovered incidentally. CTA provided excellent characterization of ACAOS features associated with coronary revascularization, including the length and severity of proximal vessel narrowing. PMID- 26848153 TI - Reduced Racial Disparity in Kidney Transplant Outcomes in the United States from 1990 to 2012. AB - Earlier studies reported inferior outcomes among black compared with white kidney transplant (KT) recipients. We examined whether this disparity improved in recent decades. Using the Scientific Registry of Transplant Recipients and Cox regression models, we compared all-cause graft loss among 63,910 black and 145,482 white adults who received a first-time live donor KT (LDKT) or deceased donor KT (DDKT) in 1990-2012. Over this period, 5-year graft loss after DDKT improved from 51.4% to 30.6% for blacks and from 37.3% to 25.0% for whites; 5 year graft loss after LDKT improved from 37.4% to 22.2% for blacks and from 20.8% to 13.9% for whites. Among DDKT recipients in the earliest cohort, blacks were 39% more likely than whites to experience 5-year graft loss (adjusted hazard ratio [aHR], 1.39; 95% confidence interval [95% CI], 1.32 to 1.47; P<0.001), but this disparity narrowed in the most recent cohort (aHR, 1.10; 95% CI, 1.03 to 1.18; P=0.01). Among LDKT recipients in the earliest cohort, blacks were 53% more likely than whites to experience 5-year graft loss (aHR, 1.53; 95% CI, 1.27 to 1.83; P<0.001), but this disparity also narrowed in the most recent cohort (aHR, 1.37; 95% CI, 1.17 to 1.61; P<0.001). Analyses revealed no statistically significant differences in 1-year or 3-year graft loss after LDKT or DDKT in the most recent cohorts. Our findings of reduced disparities over the last 22 years driven by more markedly improved outcomes for blacks may encourage nephrologists and patients to aggressively promote access to transplantation in the black community. PMID- 26848154 TI - Mitochondria are required for pro-ageing features of the senescent phenotype. AB - Cell senescence is an important tumour suppressor mechanism and driver of ageing. Both functions are dependent on the development of the senescent phenotype, which involves an overproduction of pro-inflammatory and pro-oxidant signals. However, the exact mechanisms regulating these phenotypes remain poorly understood. Here, we show the critical role of mitochondria in cellular senescence. In multiple models of senescence, absence of mitochondria reduced a spectrum of senescence effectors and phenotypes while preserving ATP production via enhanced glycolysis. Global transcriptomic analysis by RNA sequencing revealed that a vast number of senescent-associated changes are dependent on mitochondria, particularly the pro inflammatory phenotype. Mechanistically, we show that the ATM, Akt and mTORC1 phosphorylation cascade integrates signals from the DNA damage response (DDR) towards PGC-1beta-dependent mitochondrial biogenesis, contributing to aROS mediated activation of the DDR and cell cycle arrest. Finally, we demonstrate that the reduction in mitochondrial content in vivo, by either mTORC1 inhibition or PGC-1beta deletion, prevents senescence in the ageing mouse liver. Our results suggest that mitochondria are a candidate target for interventions to reduce the deleterious impact of senescence in ageing tissues. PMID- 26848155 TI - Blood Pressure Is a Major Modifiable Risk Factor Implicated in Pathogenesis of Intraplaque Hemorrhage: An In Vivo Magnetic Resonance Imaging Study. AB - OBJECTIVE: Effective prevention and management strategies of intraplaque hemorrhage (IPH) remain elusive because of our limited knowledge regarding its contributing factors. This hypothesis-generating study aimed to investigate associations between cardiovascular risk factors and IPH for improved understanding of the pathogenesis of IPH. APPROACH AND RESULTS: Asymptomatic subjects with 16% to 79% stenosis on ultrasound underwent carotid magnetic resonance imaging using a large-coverage, 3-dimensional magnetic resonance imaging protocol. Individual plaques (maximum thickness >1.5 mm) in bilateral carotid arteries were identified, and presence of IPH was determined. From 80 subjects, 176 de novo plaques were measured, of which 38 (21.6%) contained IPH. Blood pressure (BP), primarily low diastolic BP, was associated with IPH in multivariate analysis adjusted for age, sex, and plaque size (odds ratio with 95% confidence interval per 10-mm Hg increase: 0.51 [0.30-0.88]), which was little changed after adjusting for antihypertensive use and systemic atherosclerosis. Antiplatelet use was associated with IPH in age and sex-adjusted models (P=0.018), for which a trend remained after considering plaque size and past medical history (odds ratio for aspirin alone versus none: 3.1 [0.66-14.8]; odds ratio for clopidogrel or dual therapy versus none: 5.3 [0.80-35.0]; P=0.083). CONCLUSIONS: Low diastolic BP was independently associated with IPH, which was not attributed to treatment difference or BP changes from systemic atherosclerosis. Hemodynamic changes from lowering diastolic BP may be the pathophysiological link. Prospective serial studies are needed to assess whether BP and antiplatelet use are associated with the development of new or repeated IPH. PMID- 26848156 TI - Probucol-Oxidized Products, Spiroquinone and Diphenoquinone, Promote Reverse Cholesterol Transport in Mice. AB - OBJECTIVE: Oxidized products of probucol, spiroquinone and diphenoquinone, were shown to increase cell cholesterol release and plasma high-density lipoprotein (HDL) by inhibiting degradation of ATP-binding cassette transporter A1. We investigated whether these compounds enhance reverse cholesterol transport in mice. APPROACH AND RESULTS: Spiroquinone and diphenoquinone increased ATP-binding cassette transporter A1 protein (2.8- and 2.6-fold, respectively, P<0.01) and apolipoprotein A-I-mediated cholesterol release (1.4- and 1.4-fold, P<0.01 and P<0.05, respectively) in RAW264.7 cells. However, diphenoquinone, but not spiroquinone, enhanced cholesterol efflux to HDL (+12%, P<0.05), whereas both increased ATP-binding cassette transporter G1 protein, by 1.8- and 1.6-fold, respectively. When given orally to mice, both compounds significantly increased plasma HDL-cholesterol, by 19% and 20%, respectively (P<0.05), accompanied by an increase in hepatic and macrophage ATP-binding cassette transporter A1 but not ATP-binding cassette transporter G1. We next evaluated in vivo reverse cholesterol transport by injecting RAW264.7 cells labeled with (3)H-cholesterol intraperitoneally into mice. Both spiroquinone and diphenoquinone increased fecal excretion of the macrophage-derived (3)H-tracer, by 25% and 28% (P<0.01 and P<0.05), respectively. spiroquinone/diphenoquinone did not affect fecal excretion of HDL-derived (3)H-cholesterol, implying that macrophage-to-plasma was the most important step in spiroquinone/diphenoquinone-mediated promotion of in vivo reverse cholesterol transport. Finally, spiroquinone significantly reduced aortic atherosclerosis in apolipoprotein E null mice when compared with the vehicle. CONCLUSIONS: Spiroquinone and diphenoquinone increase functional ATP-binding cassette transporter A1 in both the macrophages and the liver, elevate plasma HDL cholesterol, and promote overall reverse cholesterol transport in vivo. These compounds are promising as therapeutic reagents against atherosclerosis. PMID- 26848157 TI - Platelet Control of Fibrin Distribution and Microelasticity in Thrombus Formation Under Flow. AB - OBJECTIVE: Platelet- and fibrin-dependent thrombus formation is regulated by blood flow and exposure of collagen and tissue factor. However, interactions between these blood-borne and vascular components are not well understood. APPROACH AND RESULTS: Here, we developed a method to assess whole-blood thrombus formation on microspots with defined amounts of collagen and tissue factor, allowing determination of the mechanical properties and intrathrombus composition. Confining the collagen content resulted in diminished platelet deposition and fibrin formation at high shear flow conditions, but this effect was compensated by a larger thrombus size and increased accumulation of fibrin in the luminal regions of the thrombi at the expense of the base regions. These thrombi were more dependent on tissue factor-triggered thrombin generation. Microforce nanoindentation analysis revealed a significantly increased microelasticity of thrombi with luminal-oriented fibrin. At a low shear rate, fibrin fibers tended to luminally cover the thrombi, again resulting in a higher microelasticity. Studies with blood from patients with distinct hemostatic insufficiencies indicated an impairment in the formation of a platelet-fibrin thrombus in the cases of dilutional coagulopathy, thrombocytopenia, Scott syndrome, and hemophilia B. CONCLUSIONS: Taken together, our data indicate that (1) thrombin increases the platelet thrombus volume; (2) tissue factor drives the formation of fibrin outside of the platelet thrombus; (3) limitation of platelet adhesion redirects fibrin from bottom to top of the thrombus; (4) a lower shear rate promotes thrombus coverage with fibrin; (5) the fibrin distribution pattern determines thrombus microelasticity; and (6) the thrombus-forming process is reduced in patients with diverse hemostatic defects. PMID- 26848158 TI - Lipoprotein-Associated Phospholipase A2 and Incident Peripheral Arterial Disease in Older Adults: The Cardiovascular Health Study. AB - OBJECTIVE: Although prior studies report a relationship between elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) and incident cardiovascular disease, the prospective association of Lp-PLA2 with incident peripheral arterial disease (PAD) has not been studied. We investigated the association between Lp PLA2 mass and activity and the risk of developing clinical PAD and low ankle brachial index (ABI). APPROACH AND RESULTS: Among Cardiovascular Health Study participants, a population-based cohort of 5888 adults aged >=65 years enrolled in 1989 to 1990, Lp-PLA2 mass and activity were measured in 4537 individuals without baseline PAD. Clinical PAD, defined as leg artery revascularization or diagnosed claudication, was ascertained through 2011. Incident low ABI, defined as ABI <0.9 and decline of >=0.15, was assessed among 3537 individuals who had an ABI >0.9 at baseline and a second ABI measurement 3 or 6 years later. Analyses were adjusted for demographics, cholesterol, smoking, comorbidities, and C reactive protein. Each standard deviation increment in Lp-PLA2 mass (117 ng/mL) was associated with a higher risk of developing clinical PAD (hazard ratio 1.28; 95% confidence interval 1.13, 1.45) and incident low ABI (odds ratio 1.16; 95% confidence interval 1.00, 1.33). Results per standard deviation increment in Lp PLA2 activity (13 nmol/min per mL) were similar for clinical PAD (hazard ratio 1.24; 95% confidence interval 1.07, 1.44) and low ABI (odds ratio 1.28; 95% confidence interval 1.09, 1.50). CONCLUSIONS: Higher Lp-PLA2 mass and activity were associated with development of both incident clinical PAD and low ABI. Future studies are needed to determine whether pharmacological inhibition of Lp PLA2 reduces the incidence of PAD. PMID- 26848159 TI - Cholesteryl Ester Transfer Protein Inhibition Is Not Yet Dead--Pro. AB - Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from nonatherogenic high-density lipoproteins to potentially proatherogenic non-high density lipoprotein fractions. Human genetic studies and human cohort studies have concluded that CETP gene polymorphisms associated with decreased CETP activity are accompanied by a significantly lower risk of atherosclerotic cardiovascular disease. Inhibition of CETP in rabbits reduces development of diet induced atherosclerosis. Inhibition of CETP in humans reduces non-high-density lipoprotein cholesterol while increasing high-density lipoproteins cholesterol, consistent with a reduced risk of having an atherosclerotic cardiovascular disease event. The failure of randomized human clinical outcome trials with 3 different CETP inhibitors may have been the consequence of either off-target adverse effects of the drug used or problems with the design of the trials. The hypothesis that CETP inhibition reduces atherosclerotic cardiovascular disease risk is still untested. The future of CETP inhibition as a cardio-protective strategy will depend on the outcome of the ongoing Randomized Evaluation of the Effects of Anacetrapib Through Lipid-Modification (REVEAL) trial with the CETP inhibitor, anacetrapib. PMID- 26848160 TI - Hypoxia-Inducible Factor Prolyl 4-Hydroxylase-2 Inhibition Protects Against Development of Atherosclerosis. AB - OBJECTIVE: Small-molecule hypoxia-inducible factor prolyl 4-hydroxylase (HIF-P4H) inhibitors are being explored in clinical studies for the treatment of anemia. HIF-P4H-2 (also known as PHD2 or EglN1) inhibition improves glucose and lipid metabolism and protects against obesity and metabolic dysfunction. We studied here whether HIF-P4H-2 inhibition could also protect against atherosclerosis. APPROACH AND RESULTS: Atherosclerosis development was studied in low-density lipoprotein (LDL) receptor-deficient mice treated with an oral HIF-P4H inhibitor, FG-4497, and in HIF-P4H-2-hypomorphic/C699Y-LDL receptor-mutant mice, all mice being fed a high-fat diet. FG-4497 administration to LDL receptor-deficient mice reduced the area of atherosclerotic plaques by ~50% when compared with vehicle treated controls and also reduced their weight gain, insulin resistance, liver and white adipose tissue (WAT) weights, adipocyte size, number of inflammation associated WAT macrophage aggregates and the high-fat diet-induced increases in serum cholesterol levels. The levels of atherosclerosis-protecting circulating autoantibodies against copper-oxidized LDL were increased. The decrease in atherosclerotic plaque areas correlated with the reductions in weight, serum cholesterol levels, and WAT macrophage aggregates and the autoantibody increase. FG-4497 treatment stabilized HIF-1alpha and HIF-2alpha and altered the expression of glucose and lipid metabolism and inflammation-associated genes in liver and WAT. The HIF-P4H-2-hypomorphic/C699Y-LDL receptor-mutant mice likewise had a ~50% reduction in atherosclerotic plaque areas, reduced WAT macrophage aggregate numbers, and increased autoantibodies against oxidized LDL, but did not have reduced serum cholesterol levels. CONCLUSIONS: HIF-P4H-2 inhibition may be a novel strategy for protecting against the development of atherosclerosis. The mechanisms involve beneficial modulation of the serum lipid profile and innate immune system and reduced inflammation. PMID- 26848163 TI - Ionised calcium levels in major trauma patients who received blood in the Emergency Department. AB - BACKGROUND: Exsanguination and coagulopathy remain one of the leading causes of preventable trauma related death. Low ionised calcium levels have been associated with hypotension and increased mortality and may inhibit clot formation. Blood product contains citrate that acts as a chelating agent. We hypothesised that trauma patients who have bled are at risk of hypocalcaemia and that receiving any amount of blood product can exacerbate this state. METHODS: A retrospective cohort analysis was performed on all trauma patients who had received early blood product in the ED of a single urban major trauma centre in the UK between 2013 and 2014. Ionised calcium levels were taken from venous blood gases from before and after blood product had been transfused. RESULTS: The study included 55 patients; 36 male (65%), age 33 (16-92) years, median injury severity score (ISS) 24 (4-50), units of blood product received 2 (1-16), overall mortality 18%. Fifty five per cent patients were hypocalcaemic on arrival, 89% patients were hypocalcaemic after receiving any amount of blood product. There was a statistically significant difference in ionised calcium levels after receiving blood product, pretransfusion 1.11 mmol/L (95% CI 1.09 to 1.14), post-transfusion 0.98 mmol/L (95% CI 0.93 to 1.02) (p<0.001). A fall in calcium was seen after receiving just one unit and the more units of blood product received the greater the fall seen. CONCLUSIONS: Trauma patients that have sustained blood loss are at risk of hypocalcaemia. Ionised calcium levels fall significantly further even after receiving a small amount of blood product. Prompt recognition and early targeted treatment is needed from arrival. PMID- 26848162 TI - Defining and improving the role of emergency medical services in Cape Town, South Africa. AB - INTRODUCTION: Low and middle income countries bear a disproportionate burden of paediatric morbidity and mortality. South Africa, a middle income country, has unacceptably high mortality in children less than 5 years of age. Many factors that contribute to the child mortality rate are time sensitive and require efficient access to emergency care. Delays and barriers within the emergency medical services (EMS) system increase paediatric morbidity and mortality from time sensitive illnesses. METHODS: This study is a qualitative evaluation of the prehospital care system for paediatric patients in Cape Town, South Africa. A purposive sample of healthcare personnel within and interacting with the EMS system were interviewed. A structured interview form was used to gather data. All interviews were audio recorded and transcribed; two independent reviewers performed blinded content analysis of the transcribed script. RESULTS: 33 structured interviews were conducted over a 4 week period. Eight broad themes were identified during coding, including: access, communication, community education, equipment, infrastructure, staffing, training and triage. Subcategories were used to identify areas for targeted intervention. Overall agreement between the two independent coders was 93.36%, with a kappa coefficient of 0.69. CONCLUSIONS: The prehospital system is central to delivering time sensitive care for paediatric patients. In a single centre middle income setting, communication barriers between dispatch personnel and medical facilities/EMS personnel were deemed to be a high priority intervention in order to improve care delivery. Other areas for targeted interventions should include broadening the advanced life support provider base and introducing basic medical language in dispatch staff training. PMID- 26848161 TI - Macrophage IKKalpha Deficiency Suppresses Akt Phosphorylation, Reduces Cell Survival, and Decreases Early Atherosclerosis. AB - OBJECTIVE: The IkappaB kinase (IKK) is an enzyme complex that initiates the nuclear factor kappaB transcription factor cascade, which is important in regulating multiple cellular responses. IKKalpha is directly associated with 2 major prosurvival pathways, PI3K/Akt and nuclear factor kappaB, but its role in cell survival is not clear. Macrophages play critical roles in the pathogenesis of atherosclerosis, yet the impact of IKKalpha signaling on macrophage survival and atherogenesis remains unclear. APPROACH AND RESULTS: Here, we demonstrate that genetic IKKalpha deficiency, as well as pharmacological inhibition of IKK, in mouse macrophages significantly reduces Akt S(473) phosphorylation, which is accompanied by suppression of mTOR complex 2 signaling. Moreover, IKKalpha null macrophages treated with lipotoxic palmitic acid exhibited early exhaustion of Akt signaling compared with wild-type cells. This was accompanied by a dramatic decrease in the resistance of IKKalpha(-/-) monocytes and macrophages to different proapoptotic stimuli compared with wild-type cells. In vivo, IKKalpha deficiency increased macrophage apoptosis in atherosclerotic lesions and decreased early atherosclerosis in both female and male low-density lipoprotein receptor (LDLR)(-/-) mice reconstituted with IKKalpha(-/-) hematopoietic cells and fed with the Western diet for 8 weeks compared with control LDLR(-/-) mice transplanted with wild-type cells. CONCLUSIONS: Hematopoietic IKKalpha deficiency in mouse suppresses Akt signaling, compromising monocyte/macrophage survival and this decreases early atherosclerosis. PMID- 26848164 TI - Ectopic Parathyroid Adenoma in the Carotid Sheath. AB - Primary hyperparathyroidism is predominantly caused by a single parathyroid adenoma. Knowledge of normal and ectopic locations of parathyroid glands is crucial to help guide surgeons who plan targeted unilateral parathyroidectomy to reduce surgical time and risk. We describe a female patient with clinical primary hyperparathyroidism who underwent a failed initial parathyroidectomy, with subsequent imaging localizing an ectopic parathyroid adenoma in the carotid sheath. PMID- 26848165 TI - 18F-FDG PET/CT Imaging Features of IgG4-Related Pulmonary Inflammatory Pseudotumor at Initial Diagnosis and During Early Treatment Monitoring. AB - We present a proven case of pulmonary inflammatory pseudotumor that illustrates the (18)F-FDG PET/CT imaging features of this "great mimicker of malignancy" both at initial diagnosis and during early monitoring of corticosteroid therapy, which is advocated as the first-line treatment. Although the patient showed some symptomatic response to corticosteroid therapy, as well as a modest reduction in SUVmax, complete surgical resection was eventually needed in view of the relative nonresponse. (18)F-FDG avidity in untreated cases of pulmonary inflammatory pseudotumor has been quite characteristic and may potentially be used to evaluate early response of this IgG4-related disease to nonsurgical treatment and to detect residual disease or recurrence after therapeutic intervention. PMID- 26848166 TI - 177Lu-DOTATATE PRRT in Patients with Metastatic Neuroendocrine Tumor and a Single Functioning Kidney: Tolerability and Effect on Renal Function. AB - Our objective was to assess the renal toxicity profile of (177)Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in patients with a metastatic neuroendocrine tumor (NET) and a single functioning kidney. METHODS: This was a retrospective analysis of NET patients who had undergone (177)Lu-DOTATATE PRRT at a large tertiary-care center. All patients selected for the study had somatostatin receptor-positive NETs, had received at least 3 cycles of (177)Lu DOTATATE PRRT, and had a documented single functioning kidney. The analyzed parameters included patient characteristics, metastatic burden, renal characteristics at diagnosis and during therapy, and nephrotoxic factors. For the renal assessment, the following characteristics were studied before each PRRT cycle: glomerular filtration rate (GFR) as estimated by (99m)Tc diethylenetriamine pentaacetic acid renography, effective renal plasma flow (ERPF) as measured by (99m)Tc-ethylenedicysteine renography, and blood urea and serum creatinine levels. Renal toxicity was evaluated using version 4.0 of the Common Terminology Criteria for Adverse Events (NCI-CTCAE score). The percentage reduction in GFR and ERPF was also assessed. Filtration fraction was calculated to clarify whether there was a relatively greater reduction in one index of renal function than in the other. RESULTS: At the time of analysis, 6 patients met the inclusion criteria, having received between 3 and 5 cycles of therapy with a cumulative activity of 16.6-36.2 GBq. The duration of follow-up ranged from 12 to 56 mo. The overall toxicity profile (as per the NCI-CTCAE score) showed no acute renal toxicity in any patient. Regarding overall chronic renal toxicity, 3 patients had none, 1 patient had grade II, and 2 patients had grade I. All patients with overall chronic renal toxicity showed compromised renal function at the outset (baseline). The 2 patients with grade I chronic renal toxicity after PRRT had grade II at baseline and gradual improvement over the subsequent cycles. One patient with grade II at baseline showed transient worsening to grade III after the first cycle followed by gradual improvement and a return to baseline after the second cycle. Only 2 patients showed a reduction in GFR (5.3% in one and 13.84% in the other). Four patients showed a reduction in ERPF (31.4% in the patient with the greatest reduction), and all had a rise in filtration fraction signifying that tubular parameters were more affected than glomerular parameters. CONCLUSION: With proper renal protection and dose fractionation, it is feasible to use (177)Lu-DOTATATE PRRT in patients with NET and a single functioning kidney. Further studies are required to assess the long-term renal consequences of changes in ERPF and filtration fraction in these patients. PMID- 26848167 TI - Rare Occurrence of Hypergastrinemia Due to Thoracic Neuroendocrine Tumor: Detection and Characterization by 68Ga-DOTATATE PET/CT. AB - Hypergastrinemia is a prominent feature of a segment of gastroenteropancreatic neuroendocrine tumors, the gastrinomas, occurring mostly in the gastrinoma triangle. Hypergastrinemia due to a thoracic neuroendocrine tumor is a very rare occurrence, with a paucity of literature elucidating the same. We report a case of thoracic neuroendocrine tumor in a patient who had initially presented with symptoms of peptic ulcer disease of 3-y duration. On evaluation, the patient's fasting serum gastrin levels were found to be raised. Conventional imaging modalities and endoscopic evaluation did not identify the location of a possible gastrinoma or any other mass in the abdomen. In view of the hypergastrinemia, somatostatin receptor-targeted imaging with (68)Ga-DOTATATE PET/CT was undertaken and showed a somatostatin receptor-expressing paravertebral mass next to the thoracic aorta in the left lung. The mass was excised and was histopathologically suggestive of metastatic neuroendocrine tumor (MIB-1 labeling index, 2%). The present case underscores the importance of (68)Ga-DOTATATE PET/CT in both detecting and characterizing a causative lesion missed on contrast-enhanced CT, especially when the lesion is not easily amenable to biopsy. PMID- 26848168 TI - 18-Month Performance Assessment of Gemini TF 16 PET/CT System in a High-Volume Department. AB - Acceptance testing is a set of quality control tests performed to verify various manufacturer-specified parameters before a newly installed PET/CT system can be accepted for clinical use. A new PET/CT system, Gemini TF 16, installed in our department in September 2012 has a PET component capable of time-of-flight imaging using lutetium-yttrium-oxyorthosilicate crystals and operates in 3 dimensional mode. Our aim was to evaluate the system before acceptance and observe the consistency of its performance during high-volume work for 18 mo after installation (we perform an average of 30 PET/CT scans daily). METHODS: We performed NEMA (National Electrical Manufacturers Association) NU-2 2007 acceptance testing on the Gemini TF 16; continuously evaluated its gain calibration, timing resolution, and energy resolution during the subsequent 18 mo; and analyzed the results. RESULTS: The system passed the acceptance testing and showed few fluctuations in energy and timing resolutions during the observation period. CONCLUSION: The Gemini TF 16 whole-body PET/CT system performed excellently during the 18-mo study period despite the high volume of work. PMID- 26848169 TI - Molecular imaging of 1p/19q deletion in oligodendroglial tumours with 11C methionine positron emission tomography. AB - OBJECTIVE: Chromosome 1p/19q deletion is an established prognostic and predictive marker in the WHO grade III oligodendroglial tumours (OT). To estimate the genetic status preoperatively, the authors investigated the correlation between the uptake of (11)C-methionine in positron emission tomography (PET) and the 1p/19q status in grades II and III OT. METHODS: We retrospectively reviewed 144 patients with gliomas who received (11)C-methionine PET. 66 cases with grades II III oligodendrogliomas or oligoastrocytomas underwent fluorescence in situ hybridisation to determine the 1p/19q status. The tissue uptake of (11)C methionine was expressed as the ratio of the maximum standardised uptake value (SUVmax) in tumour areas to the mean SUV (SUVmean) in the contralateral normal brain (tumour-to-normal tissue (T/N) ratio). RESULTS: The T/N ratio in (11)C methionine PET was significantly higher in grade III OT than in grade II tumours. The mean T/N ratio of the grade II tumours without 1p/19q deletion was significantly higher than that of the grade II tumours with 1p/19q deletion (mean 2.67 vs 1.94, respectively; p=0.0457). In grade III tumours, the mean T/N ratio of the tumours without 1p/19q deletion was also significantly higher than that of the tumours with 1p/19q deletion (mean 4.83 vs 3.49, respectively; p=0.0261). The rate of IDH1 mutation was lower and the rate of contrast enhancement on MRIs was higher in the 1p/19q non-deleted OT than those with 1p/19q deletion, which may contribute to the high T/N ratio. CONCLUSIONS: Among suspected OT, (11)C methionine PET may help us preoperatively discriminate tumours with and without 1p/19q deletion. PMID- 26848170 TI - Differences in globus pallidus neuronal firing rates and patterns relate to different disease biology in children with dystonia. AB - BACKGROUND: The pathophysiology underlying different types of dystonia is not yet understood. We report microelectrode data from the globus pallidus interna (GPi) and globus pallidus externa (GPe) in children undergoing deep brain stimulation (DBS) for dystonia and investigate whether GPi and GPe firing rates differ between dystonia types. METHODS: Single pass microelectrode data were obtained to guide electrode position in 44 children (3.3-18.1 years, median 10.7) with the following dystonia types: 14 primary, 22 secondary Static and 8 progressive secondary to neuronal brain iron accumulation (NBIA). Preoperative stereotactic MRI determined coordinates for the GPi target. Digitised spike trains were analysed offline, blind to clinical data. Electrode placement was confirmed by a postoperative stereotactic CT scan. FINDINGS: We identified 263 GPi and 87 GPe cells. Both GPi and GPe firing frequencies differed significantly with dystonia aetiology. The median GPi firing frequency was higher in the primary group than in the secondary static group (13.5 Hz vs 9.6 Hz; p=0.002) and higher in the NBIA group than in either the primary (25 Hz vs 13.5 Hz; p=0.006) or the secondary static group (25 Hz vs 9.6 Hz; p=0.00004). The median GPe firing frequency was higher in the NBIA group than in the secondary static group (15.9 Hz vs 7 Hz; p=0.013). The NBIA group also showed a higher proportion of regularly firing GPi cells compared with the other groups (p<0.001). A higher proportion of regular GPi cells was also seen in patients with fixed/tonic dystonia compared with a phasic/dynamic dystonia phenotype (p<0.001). The GPi firing frequency showed a positive correlation with 1-year outcome from DBS measured by improvement in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-m) score (p=0.030). This association was stronger for the non-progressive patients (p=0.006). INTERPRETATION: Pallidal firing rates and patterns differ significantly with dystonia aetiology and phenotype. Identification of specific firing patterns may help determine targets and patient-specific protocols for neuromodulation therapy. FUNDING: National Institute of Health Research, Guy's and St. Thomas' Charity, Dystonia Society UK, Action Medical Research, German National Academic Foundation. PMID- 26848171 TI - The prediagnostic phase of Parkinson's disease. AB - The field of prediagnostic Parkinson's disease (PD) is fast moving with an expanding range of clinical and laboratory biomarkers, and multiple strategies seeking to discover those in the earliest stages or those 'at risk'. It is widely believed that the highest likelihood of securing neuroprotective benefit from drugs will be in these subjects, preceding current point of diagnosis of PD. In this review, we outline current knowledge of the prediagnostic phase of PD, including an up-to-date review of risk factors (genetic and environmental), their relative influence, and clinical features that occur prior to diagnosis. We discuss imaging markers across a range of modalities, and the emerging literature on fluid and peripheral tissue biomarkers. We then explore current initiatives to identify individuals at risk or in the earliest stages that might be candidates for future clinical trials, what we are learning from these initiatives, and how these studies will bring the field closer to realistically commencing primary or secondary preventive trials for PD. Further progress in this field hinges on greater clinical and biological description, and understanding of the prediagnostic, peridiagnostic and immediate postdiagnostic stages of PD. Identifying subjects 3-5 years before they are currently diagnosed may be an ideal group for neuroprotective trials. At the very least, these initiatives will help clarify the stage before and around diagnosis, enabling the field to push into unchartered territory at the earliest stages of disease. PMID- 26848172 TI - Biodistribution and PET Imaging of Labeled Bispecific T Cell-Engaging Antibody Targeting EpCAM. AB - AMG 110, a bispecific T cell engager (BiTE) antibody construct, induces T cell mediated cancer cell death by cross-linking epithelial cell adhesion molecule (EpCAM) on tumor cells with a cluster of differentiation 3 epsilon (CD3epsilon) on T cells. We labeled AMG 110 with (89)Zr or near-infrared fluorescent dye (IRDye) 800CW to study its tumor targeting and tissue distribution. METHODS: Biodistribution and tumor uptake of (89)Zr-AMG 110 was studied up to 6 d after intravenous administration to nude BALB/c mice bearing high EpCAM-expressing HT 29 colorectal cancer xenografts. Tumor uptake of (89)Zr-AMG 110 was compared with uptake in head and neck squamous cell cancer FaDu (intermediate EpCAM) and promyelocytic leukemia HL60 (EpCAM-negative) xenografts. Intratumoral distribution in HT-29 tumors was studied using 800CW-AMG 110. RESULTS: Tumor uptake of (89)Zr-AMG 110 can be clearly visualized using small-animal PET imaging up to 72 h after injection. The highest tumor uptake of (89)Zr-AMG 110 at the 40 MUg dose level was observed at 6 and 24 h (respectively, 5.35 +/- 0.22 and 5.30 +/- 0.20 percentage injected dose per gram; n = 3 and 4). Tumor uptake of (89)Zr AMG 110 was EpCAM-specific and correlated with EpCAM expression. 800CW-AMG 110 accumulated at the tumor cell surface in viable EpCAM-expressing tumor tissue. CONCLUSION: PET and fluorescent imaging provided real-time information about AMG 110 distribution and tumor uptake in vivo. Our data support using (89)Zr and IRDye 800CW to evaluate tumor and tissue uptake kinetics of bispecific T cell engager antibody constructs in preclinical and clinical settings. PMID- 26848173 TI - High-Sensitivity and High-Resolution SPECT/CT Systems Provide Substantial Dose Reduction Without Compromising Quantitative Precision for Assessment of Myocardial Perfusion and Function. AB - There is increasing concern about radiation exposure from myocardial perfusion SPECT (MPS). gamma-cameras with solid-state cadmium-zinc-telluride (CZT) detectors have better count sensitivity and spatial resolution than conventional sodium iodine detectors, allowing for significant reductions in radiotracer dose or acquisition time. This study aimed to demonstrate the capability of a hybrid CZT SPECT/64-slice CT system for dose reduction and to determine the maximal reduction possible without compromising image quality or the quantification precision of clinical MPS. METHODS: The imaging data of patients with normal myocardial perfusion and 30 patients with mid-sized to large perfusion defects who had undergone stress (99m)Tc-tetrofosmin MPS were postprocessed. Low-dose (361 +/- 60 MBq) and high-dose (725 +/- 142 MBq) (99m)Tc-tetrofosmin scans were included, with 6-min and 4-min scanning times, respectively. List-mode SPECT data were reconstructed with CT-based attenuation correction and with full as well as 50% and 75% reductions in acquisition time to simulate the corresponding relative dose reductions. The reconstructed SPECT images were analyzed to calculate global MPS defect size and regional defect size for 3 coronary artery territories-left anterior descending, left circumflex, and right-as well as left ventricular (LV) volume and ejection fraction. RESULTS: For patients with normal MPS results, there were no differences in defect size, LV volume, or ejection fraction, regardless of whether 50% or 75% reduction was used. For patients with abnormal MPS results, at a 50% reduction there was a significant difference in global defect size but not in regional defect size in the left anterior descending, left circumflex, and right coronary artery territories, whereas at a 75% reduction the difference was statistically significant in all territories, including the difference in global defect size. Nonetheless, differences in the defect size were minimal. The LV end-diastolic and end-systolic volumes and LV ejection fraction were not significantly different, regardless of whether 50% or 75% dose reduction was used. CONCLUSION: Ultra-low-dose (<190 MBq) MPS even with short imaging times (<6 min) is feasible using a hybrid CZT SPECT/CT camera without compromising image quality or significantly altering quantification of myocardial perfusion or LV function. We demonstrated that an additional 50% reduction in the current low-dose recommendations from the American Society of Nuclear Cardiology guidelines for (99m)Tc-labeled MPS is highly feasible while retaining short imaging protocols. PMID- 26848174 TI - Quantitative and Simplified Analysis of 11C-Erlotinib Studies. AB - Quantitative assessment of (11)C-erlotinib uptake may be useful in selecting non small cell lung cancer (NSCLC) patients for erlotinib therapy. The purpose of this study was to find the optimal pharmacokinetic model for quantification of uptake and to evaluate various simplified methods for routine analysis of (11)C erlotinib uptake in NSCLC patients. METHODS: Dynamic (15)O-H2O and (11)C erlotinib scans were obtained in 17 NSCLC patients, 8 with and 9 without an activating epidermal growth factor receptor mutation (exon 19 deletion or exon 21 point mutation). Ten of these subjects also underwent a retest scan on the same day. (11)C-erlotinib data were analyzed using single-tissue and 2-tissue irreversible and -reversible (2T4k) plasma input models. In addition, several advanced models that account for uptake of radiolabeled metabolites were evaluated, including a variation of the 2T4k model without correcting for metabolite fractions in plasma (2T4k-WP). Finally, simplified methods were evaluated-that is, SUVs and tumor-to-blood ratios (TBR)-for several scan intervals. RESULTS: Tumor kinetics were best described using the 2T4k-WP model yielding optimal fits to the data (Akaike preference, 43.6%), acceptable test retest variability (12%), no dependence on perfusion changes, and the expected clinical group separation (P < 0.016). Volume of distribution estimated using 2T4k-WP and 2T4k were highly correlated (R(2) = 0.94). Similar test-retest variabilities and clinical group separations were found. The 2T4k model did not perform better than an uncorrected model (2T4k-WP), probably because of uncertainty in the estimation of true metabolite fractions. Investigation of simplified approaches showed that SUV curves normalized to patient weight, and injected tracer dose did not reach equilibrium within the time of the scan. In contrast, TBR normalized to whole blood (TBR-WB) appeared to be a useful outcome measure for quantitative assessment of (11)C-erlotinib scans acquired 40-60 min after injection. CONCLUSION: The optimal model for quantitative assessment of (11)C-erlotinib uptake in NSCLC was the 2T4k-WB model. The preferred simplified method was TBR-WB (40-60 min after injection) normalized using several whole blood samples. PMID- 26848175 TI - Synthesis and Preclinical Evaluation of 11C-UCB-J as a PET Tracer for Imaging the Synaptic Vesicle Glycoprotein 2A in the Brain. AB - The synaptic vesicle glycoprotein 2A (SV2A) is found in secretory vesicles in neurons and endocrine cells. PET with a selective SV2A radiotracer will allow characterization of drugs that modulate SV2A (e.g., antiepileptic drugs) and potentially could be a biomarker of synaptic density (e.g., in neurodegenerative disorders). Here we describe the synthesis and characterization of the SV2A PET radiotracer (11)C-UCB-J ((R)-1-((3-((11)C-methyl-(11)C)pyridin-4-yl)methyl)-4 (3,4,5-trifluorophenyl)pyrrolidin-2-one) in nonhuman primates, including whole body biodistribution. METHODS: (11)C-UCB-J was prepared by C-(11)C-methylation of the 3-pyridyl trifluoroborate precursor with (11)C-methyl iodide via the Suzuki Miyaura cross-coupling method. Rhesus macaques underwent multiple scans including coinjection with unlabeled UCB-J (17, 50, and 150 MUg/kg) or preblocking with the antiepileptic drug levetiracetam at 10 and 30 mg/kg. Scans were acquired for 2 h with arterial sampling and metabolite analysis to measure the input function. Regional volume of distribution (VT) was estimated using the 1-tissue-compartment model. Target occupancy was assessed using the occupancy plot; the dissociation constant (Kd) was determined by fitting self-blocking occupancies to a 1-site model, and the maximum number of receptor binding sites (Bmax) values were derived from baseline VT and from the estimated Kd and the nondisplaceable distribution volume (VND). RESULTS: (11)C-UCB-J was synthesized with greater than 98% purity. (11)C-UCB-J exhibited high free fraction (0.46 +/- 0.02) and metabolized at a moderate rate (39% +/- 5% and 24% +/- 3% parent remaining at 30 and 90 min) in plasma. In the monkey brain, (11)C-UCB-J displayed high uptake and fast kinetics. VT was high (~25-55 mL/cm(3)) in all gray matter regions, consistent with the ubiquitous expression of SV2A. Preblocking with 10 and 30 mg/kg of levetiracetam resulted in approximately 60% and 90% occupancy, respectively. Analysis of the self-blocking scans yielded a Kd estimate of 3.4 nM and Bmax of 125-350 nM, in good agreement with the in vitro inhibition constant (Ki) of 6.3 nM and regional Bmax in humans. Whole-body biodistribution revealed that the liver and the brain are the dose-limiting organs for males and females, respectively. CONCLUSION: (11)C-UCB-J exhibited excellent characteristics as an SV2A PET radiotracer in nonhuman primates. The radiotracer is currently undergoing first-in-human evaluation. PMID- 26848176 TI - Intratumorally Injected 177Lu-Labeled Gold Nanoparticles: Gold Nanoseed Brachytherapy with Application for Neoadjuvant Treatment of Locally Advanced Breast Cancer. AB - Improvements in the treatment of locally advanced breast cancer (LABC) are needed. Our objective was to study a radiation nanomedicine (gold nanoseeds) composed of 30-nm gold nanoparticles (AuNP) modified with polyethyleneglycol (PEG) chains linked to DOTA for complexing the beta-particle emitter (177)Lu and to panitumumab for targeting epidermal growth factor receptors (EGFR) ((177)Lu-T AuNP) as a novel neoadjuvant brachytherapy for LABC. Nontargeted gold nanoseeds ((177)Lu-NT-AuNP) were constructed without panitumumab for comparison. METHODS: (177)Lu-T-AuNP or (177)Lu-NT-AuNP was injected intratumorally in CD-1 athymic mice bearing subcutaneous EGFR-positive MDA-MB-468 human breast cancer tumors. Biodistribution and small-animal SPECT/CT imaging studies were performed to evaluate tumor and normal organ localization. A short-term (15 d) study was conducted to select the most effective amount of (177)Lu-T-AuNP or (177)Lu-NT AuNP for treatment with long-term observation (90-120 d). Normal organ toxicities were assessed by monitoring body weight, blood cell counts, and serum alanine aminotransferase and creatinine. Radiation-absorbed doses in the tumor and normal organs were estimated by Monte Carlo N-Particle version 5.0 modeling. RESULTS: Tumor radioactivity concentrations were high at 1 h after injection (>300-400 percentage injected dose per gram [%ID/g]) but decreased by 2-3-fold at 48 h after injection. Normal organ uptake was low (<0.5 %ID/g) except for the liver and spleen (<3 %ID/g), increasing by 2-5-fold at 48 h after injection. Treatment with 4.5 MBq (6 * 10(11) AuNP) of (177)Lu-T-AuNP or (177)Lu-NT-AuNP arrested tumor growth over 90 d without normal organ toxicity, whereas tumors continued to grow in mice treated with unlabeled T-AuNP or (177)Lu-labeled PEG polymer not linked to AuNP. Survival was prolonged up to 120 d in mice treated with (177)Lu-T AuNP or (177)Lu-NT-AuNP. Radiation-absorbed doses to the tumor were 30 and 22 Gy for (177)Lu-T-AuNP and (177)Lu-NT-AuNP, respectively. Some tumor regions received high radiation doses (250-1,300 Gy). Normal organ doses were low (0.04-0.6 Gy). CONCLUSION: Gold nanoseeds injected intratumorally were highly effective for inhibiting the growth of breast cancer tumors in CD-1 athymic mice and caused no normal organ toxicity. These results are promising for their application for neoadjuvant brachytherapy of LABC. Because EGFR targeting was not required, the approach is broadly applicable to LABC with different phenotypes. PMID- 26848177 TI - A tetraspanin regulates septate junction formation in Drosophila midgut. AB - Septate junctions (SJs) are membrane specializations that restrict the free diffusion of solutes through the paracellular pathway in invertebrate epithelia. In arthropods, two morphologically different types of septate junctions are observed; pleated (pSJs) and smooth (sSJs), which are present in ectodermally and endodermally derived epithelia, respectively. Recent identification of sSJ specific proteins, Mesh and Ssk, in Drosophila indicates that the molecular compositions of sSJs and pSJs differ. A deficiency screen based on immunolocalization of Mesh identified a tetraspanin family protein, Tsp2A, as a newly discovered protein involved in sSJ formation in Drosophila Tsp2A specifically localizes at sSJs in the midgut and Malpighian tubules. Compromised Tsp2A expression caused by RNAi or the CRISPR/Cas9 system was associated with defects in the ultrastructure of sSJs, changed localization of other sSJ proteins, and impaired barrier function of the midgut. In most Tsp2A mutant cells, Mesh failed to localize to sSJs and was distributed through the cytoplasm. Tsp2A forms a complex with Mesh and Ssk and these proteins are mutually interdependent for their localization. These observations suggest that Tsp2A cooperates with Mesh and Ssk to organize sSJs. PMID- 26848178 TI - Corrigendum. PMID- 26848179 TI - Corrigendum. PMID- 26848180 TI - Apiose: one of nature's witty games. AB - Apiose is a unique branched-chain pentose found principally in plants. It is a key component of structurally complex cell wall polysaccharides, as well as being present in a large number of naturally occurring secondary metabolites. This review provides a comprehensive overview of the current state of knowledge on the metabolism and natural occurrence of apiose, using cyanogenic glycosides and their related compounds as a case study. The biological function of apiose and of apiosylated compounds is discussed. PMID- 26848181 TI - Role of bismuth in improving Helicobacter pylori eradication with triple therapy. AB - In most regions of the world, antimicrobial resistance has increased to the point where empirical standard triple therapy for Helicobacter pylorieradication is no longer recommended. The treatment outcome in a population is calculated as the sum of the treatment success in the subpopulation with susceptible infections plus treatment success in the subpopulation with resistant infections. The addition of bismuth (i.e., 14-day triple therapy plus bismuth) can improve cure rates despite a high prevalence of antimicrobial resistance. The major bismuth effect is to add an additional 30%-40% to the success with resistant infections. The overall result is therefore dependent on the prevalence of resistance and the treatment success in the subpopulation with resistant infections (eg, with proton pump inhibitor-amoxicillin dual therapy). Here, we explore the contribution of each component and the mechanisms of how bismuth might enhance the effectiveness of triple therapy. We also discuss the limitations of this approach and provide suggestions how triple therapy plus bismuth might be further improved. PMID- 26848182 TI - Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD. AB - OBJECTIVE: Iron deficiency is a common complication in patients with IBD and oral iron therapy is suggested to exacerbate IBD symptoms. We performed an open labelled clinical trial to compare the effects of per oral (PO) versus intravenous (IV) iron replacement therapy (IRT). DESIGN: The study population included patients with Crohn's disease (CD; N=31), UC (N=22) and control subjects with iron deficiency (non-inflamed, NI=19). After randomisation, participants received iron sulfate (PO) or iron sucrose (IV) over 3 months. Clinical parameters, faecal bacterial communities and metabolomes were assessed before and after intervention. RESULTS: Both PO and IV treatments ameliorated iron deficiency, but higher ferritin levels were observed with IV. Changes in disease activity were independent of iron treatment types. Faecal samples in IBD were characterised by marked interindividual differences, lower phylotype richness and proportions of Clostridiales. Metabolite analysis also showed separation of both UC and CD from control anaemic participants. Major shifts in bacterial diversity occurred in approximately half of all participants after IRT, but patients with CD were most susceptible. Despite individual-specific changes in phylotypes due to IRT, PO treatment was associated with decreased abundances of operational taxonomic units assigned to the species Faecalibacterium prausnitzii, Ruminococcus bromii, Dorea sp. and Collinsella aerofaciens. Clear IV-specific and PO-specific fingerprints were evident at the level of metabolomes, with changes affecting cholesterol-derived host substrates. CONCLUSIONS: Shifts in gut bacterial diversity and composition associated with iron treatment are pronounced in IBD participants. Despite similar clinical outcome, oral administration differentially affects bacterial phylotypes and faecal metabolites compared with IV therapy. TRIAL REGISTRATION NUMBER: clinicaltrial.gov (NCT01067547). PMID- 26848183 TI - Titanium dioxide nanoparticles exacerbate DSS-induced colitis: role of the NLRP3 inflammasome. AB - OBJECTIVE: Western lifestyle and diet are major environmental factors playing a role in the development of IBD. Titanium dioxide (TiO2) nanoparticles are widely used as food additives or in pharmaceutical formulations and are consumed by millions of people on a daily basis. We investigated the effects of TiO2 in the development of colitis and the role of the nucleotide-binding oligomerisation domain receptor, pyrin domain containing (NLRP)3 inflammasome. DESIGN: Wild-type and NLRP3-deficient mice with dextran sodium sulfate-induced colitis were orally administered with TiO2 nanoparticles. The proinflammatory effects of TiO2 particles in cultured human intestinal epithelial cells (IECs) and macrophages were also studied, as well as the ability of TiO2 crystals to traverse IEC monolayers and accumulate in the blood of patients with IBD using inductively coupled plasma mass spectrometry. RESULTS: Oral administration of TiO2 nanoparticles worsened acute colitis through a mechanism involving the NLRP3 inflammasome. Importantly, crystals were found to accumulate in spleen of TiO2 administered mice. In vitro, TiO2 particles were taken up by IECs and macrophages and triggered NLRP3-ASC-caspase-1 assembly, caspase-1 cleavage and the release of NLRP3-associated interleukin (IL)-1beta and IL-18. TiO2 also induced reactive oxygen species generation and increased epithelial permeability in IEC monolayers. Increased levels of titanium were found in blood of patients with UC having active disease. CONCLUSION: These findings indicate that individuals with a defective intestinal barrier function and pre-existing inflammatory condition, such as IBD, might be negatively impacted by the use of TiO2 nanoparticles. PMID- 26848185 TI - Safety and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary intervention. AB - OBJECTIVE: The effects of ticagrelor in the subpopulation of patients with ST elevation myocardial infarction (STEMI) were consistent with those observed in the overall Platelet Inhibition and Patient Outcomes (PLATO) study. However, this subgroup included patients initially or ultimately treated conservatively. The aim of this study is to compare treatment using ticagrelor with treatment using clopidogrel in patients with STEMI undergoing primary percutaneous coronary intervention (PCI). METHODS: This post-hoc subgroup analysis compared ticagrelor with clopidogrel in 4949 PLATO patients with STEMI that were treated with primary PCI within 12 h of admission. The primary endpoint was cardiovascular death, myocardial infarction or stroke. The safety endpoint consisted of any major bleeding. Secondary endpoints included stent thrombosis. The analysis was not adequately powered to establish significance of any treatment effects. RESULTS: During a median of 286 days, the primary endpoint occurred in 7.9% of ticagrelor treated patients versus 8.6% of clopidogrel-treated patients (HR 0.91, 95% CI 0.75 to 1.12, p=0.38). Major bleeding occurred in 6.7% in ticagrelor-treated patients versus 6.8% of clopidogrel-treated patients (HR 0.97, 95% CI 0.77 to 1.22, p=0.79). No interactions were observed for the treatment effect of ticagrelor versus clopidogrel on the primary efficacy (p=0.40) and primary safety endpoints (p=0.15) as compared with the full PLATO population. Treatment with ticagrelor versus clopidogrel reduced the occurrence of definite stent thrombosis (HR 0.58, 95% CI 0.37 to 0.89, p=0.013). CONCLUSIONS: In the subset of patients with STEMI treated with primary PCI, ticagrelor compared with clopidogrel was safe, and efficacy outcomes were consistent with the overall PLATO trial. TRIAL REGISTRATION NUMBER: NCT00391872; Results. PMID- 26848186 TI - Heterogeneity of aortic disease severity in patients with Loeys-Dietz syndrome. AB - OBJECTIVE: This study aimed to determine aortic disease severity in patients with Loeys-Dietz syndrome (LDS). METHODS: Thirty-three patients with LDS diagnosed and followed up at our unit were included. After reviewing all family trees, 25 deceased family members with clear clinical suspicion of having had LDS were also included. Clinical presentation, aortic dilation rate by echocardiography and age at aortic surgery, dissection or death were determined. RESULTS: Median aortic diameter at diagnosis was 36 mm, 43% of the patients aged >40 years had a z-score <2. Median aortic root dilation rate was 0.67 mm/year (maximum 2.0 mm/year) over a median follow-up of 2 years (IQR 1.0-4.0). In the global cohort, 31/58 patients reached a clinical endpoint; 19% death, median age: 52 years; 14% dissection, median age: 36 years; 21% aortic surgery, median age: 53 years. As expected, probands had a higher z-score (2.9 vs 1.5, p=0.019) and more often required aortic surgery (33.4% vs 18.2%, p=0.035) compared with family members. TGFBR2 carriers had a higher z-score compared with TGFBR1 carriers (3.2 vs 1.5, p=0.034) and younger age at aortic surgery (HR 4.9, 95% CI 1.5 to 123, p=0.026). Craniofacial severity index was inversely correlated with age at first event (r= 0.765, p=0.045). CONCLUSIONS: Although paediatric patients were not properly represented in our cohort, our patients with LDS presented a significant heterogeneity in the severity of aortic disease with large intrafamilial and interfamilial variability, aortic root aneurysm were less frequent and aortic complications less premature than previously depicted. Furthermore, aortic dilation rate was similar to that reported in Marfan syndrome and aortic root diameters appear to be larger in TGFBR2 carriers. PMID- 26848187 TI - Protein kinase A inhibitor, H89, enhances survival and clonogenicity of dissociated human embryonic stem cells through Rho-associated coiled-coil containing protein kinase (ROCK) inhibition. AB - STUDY QUESTION: Can cell survival of dissociated human embryonic stem cells (hESCs) be increased during culture? SUMMARY ANSWER: A protein kinase A (PKA) inhibitor, H89, can significantly enhance survival and clonogenicity of dissociated hESCs without affecting their pluripotency. WHAT IS KNOWN ALREADY: hESCs are vulnerable to massive cell death upon cellular detachment and dissociation. STUDY DESIGN, SIZE, DURATION: hESCs were dissociated into single cells and then cultured in feeder-dependent and -independent manners. H89 was added to the culture medium at different concentrations for 1 day. The statistical results were obtained from at least three independent experiments (n >= 4). The group without treatment was used as the negative control. PARTICIPANTS/MATERIALS, SETTING, METHODS: 4 uM H89 was added in the culture medium to promote cell survival and colony formation of dissociated hESCs. MTT method and propidium iodide (PI) staining were used to determine cell proliferation, cell death and cell cycle, respectively. To count colony formation, alkaline phosphatase (AP) staining was carried out. Western blot was performed to determine protein expression. Except AP staining, immunofluorescence, RT-PCR and karyotype analysis were used to confirm the pluripotent state of H89 treated hESCs. MAIN RESULTS AND THE ROLE OF CHANCE: H89 inhibits the dissociation-induced phosphorylation of PKA and two substrates of Rho-associated coiled-coil containing protein kinase (ROCK), myosin light chain (MLC2) and myosin phosphatase target subunit 1 (MYPT1), significantly increases cell survival and colony formation, and strongly depresses dissociation-induced cell death and cell blebbing without affecting the pluripotency of hESCs and their differentiation in vitro. LIMITATIONS, REASONS FOR CAUTION: Appropriate H89 concentration should be used and 1 day of H89 treatment is sufficient for promoting survival and colony formation of dissociated hESCs. WIDER IMPLICATIONS OF THE FINDINGS: These results provide an alternative for human pluripotent stem cell (hPSC) culture, broaden the scope of participants in the cell death of single hES cells after dissociation and further enlighten clues to understand the mechanism of dissociation-induced cell death. STUDY FUNDING/COMPETING INTERESTS: This research was supported by the National Natural Science Foundation of China (21176238, 21576266), and Chinese Academy of Sciences. There is no conflict of interest to declare. TRIAL REGISTRATION NUMBER: Nil. PMID- 26848189 TI - Idiopathic aneurysm of the pulmonary artery in a patient with coronary disease. PMID- 26848188 TI - Cryopreservation of in vitro matured oocytes in addition to ovarian tissue freezing for fertility preservation in paediatric female cancer patients before and after cancer therapy. AB - STUDY QUESTION: Is a protocol that combines in vitro maturation of germinal vesicle-stage oocytes and their vitrification with freezing of cortical ovarian tissue feasible for use in fertility preservation for both chemotherapy-naive paediatric patients as well as patients after initiation of cancer therapy? SUMMARY ANSWER: Follicle-containing ovarian tissue as well as oocytes that can undergo maturation in vitro can be obtained from paediatric patients (including prepubertal girls) both before and after cancer therapy. WHAT IS KNOWN ALREADY: Anticancer therapy reduces the number of follicles/oocytes but this effect is less severe in young patients, particularly the paediatric age group. Autotransplantation of ovarian tissue has yielded to date 60 live births, including one from tissue that was cryostored in adolescence. However, it is assumed that autografting cryopreserved-thawed ovarian cortical tissue poses a risk of reseeding the malignancy. Immature oocytes can be collected from very young girls without hormonal stimulation and then matured in vitro and vitrified. We have previously shown that there is no difference in the number of ovarian cortical follicles between paediatric patients before and after chemotherapy. STUDY DESIGN, SIZE, DURATION: A prospective study was conducted in a cohort of 42 paediatric females with cancer (before and after therapy initiation) who underwent fertility preservation procedures in 2007-2014 at a single tertiary medical centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study group included girls and adolescent females with cancer: 22 before and 20 after chemotherapy. Following partial or complete oophorectomy, immature oocytes were either aspirated manually ex vivo from visible small antral follicles or filtered from spent media. Oocytes were incubated in oocyte maturation medium, and those that matured at 24 or 48 h were vitrified. Ovarian cortical tissue was cut and prepared for slow-gradual cryopreservation. Anti-Mullerian hormone (AMH) levels were measured in serum before and after oophorectomy. MAIN RESULTS AND ROLE OF CHANCE: Ovarian tissue was successfully collected from 78.7% of the 42 patients. Oocytes were obtained from 20 patients before chemotherapy and 13 after chemotherapy. The youngest patients from whom oocytes were retrieved were aged 2 years (two atretic follicles) and 3 years. Of the 395 oocytes collected, ~30% were atretic (29.6% in the pre-chemotherapy group, 37% in the post-chemotherapy group). One hundred twenty-one oocytes (31%) were matured in vitro and vitrified: 67.8% from patients before chemotherapy, the rest after chemotherapy. Mature oocytes suitable for vitrification were obtained from 16/20 patients before chemotherapy and from 12/13 patients after chemotherapy (maturation rate, 32 and 26.4%, respectively). There were significant correlations of the number of vitrified oocytes with patient age (more matured oocytes with older age) (P = 0.001) and with pre-oophorectomy AMH levels (P = 0.038 pre-chemotherapy group, P = 0.029 post-chemotherapy group). Oocytes suitable for vitrification were obtained both by manual aspiration of antral follicles (45%) and from rinse solutions after dissection. There were significantly more matured oocytes in the pre-chemotherapy group from aspiration than in the post-chemotherapy group after both aspiration (P < 0.033) and retrieval from rinsing fluids (P < 0.044). The number of pre-antral follicles per histological section did not differ in the pre versus post-chemotherapy. AMH levels dropped by approximately 50% after ovarian removal in both groups, with a significant correlation between pre- and post oophorectomy levels (P = 0.002 pre-chemotherapy group, P = 0.001 post chemotherapy group). LIMITATIONS, REASONS FOR CAUTION: There were no patients between 5 years and 10 years old in the post-chemotherapy group, which might have affected some results and correlations. Oocytes from patients soon after chemotherapy might be damaged, and caution is advised when using them for fertility-restoration purposes. The viability, development capability and fertilization potential of oocytes from paediatric patients, especially prepubertal and after chemotherapy, are unknown, in particular oocytes recovered from the media after the tissue dissection step. WIDER IMPLICATIONS OF THE FINDINGS: Although more oocytes were collected and matured from chemotherapy naive paediatric patients, ovarian tissue and immature oocytes were also retrieved from young girls in whom cancer therapy has already been initiated. Our centre has established a protocol for potential maximal fertility preservation in paediatric female patients with cancer. Vitrified-in vitro-matured oocytes may serve as an important gamete source in paediatric female patients with cancer because the risk of reseeding the disease is avoided. Further studies are needed on the fertility-restoring potential of oocytes from paediatric and prepubertal patients, especially after exposure to chemotherapy. STUDY FUNDING/COMPETING INTERESTS: The study was conducted as part of the routine procedures for fertility preservation at our IVF unit. No funding outside of the IVF laboratory was received. Funding for the AMH measurements was obtained by a research grant from the Israel Science Foundation (to B.-A.I., ISF 13-1873). None of the authors have competing interests. TRIAL REGISTRATION NUMBER: N/A. PMID- 26848191 TI - Effect of Specific Oil Surface Area on the Thermal Stressing of Rapeseed Oil During Heating in an Electric Frying Pan. AB - The effect of specific oil surface (SOS) during pan frying of rapeseed oil on its thermal stability and antioxidant capacity (AC) was evaluated. Rapeseed oils with different oil layer heights (OLH = 0.5, 1.0, 1.5, 2.0, and 2.5 cm) were heated on an electric frying pan coated with Teflon at 180 +/- 10 degrees C until a selected end point of 25 % total polar compounds (TPC) was reached. The changes of chemical parameters of oil samples such as peroxide value, p-anisidine value, Totox value, free fatty acids, TPC and AC using the 2,2-diphenyl-1-picrylhydrazyl assay were determined. Irrespective of the applied methods, the highest changes in oil with OLH = 0.5 cm were observed. Heating in low OLH also led to the fastest time of TPC formation in rapeseed oil; the 0.5-cm layer reached 25 % TPC in a relatively short time (71.5 min) compared to the highest OLH = 2.5 cm (t = 315.1 min). The SOS and the rate of change in the heated oils decreased with increasing OLH. Crucial effects of SOS on physicochemical oil changes were observed. The present study demonstrated the protective effect of increasing the OLH on the quality of the heated rapeseed oils. PMID- 26848190 TI - Acute aortic dissection involving the root: operative and long-term outcome after curative proximal repair. AB - OBJECTIVES: The aim of the study was to evaluate operative and long-term results after surgery of acute aortic dissection involving the root, in which the proximal repair consisted of curative resection of all dissected aortic sinuses and was performed using either valve-sparing root repair or complete root replacement with a valve conduit. METHODS: Between August 2002 and March 2013, 162 consecutive patients (mean age 63 +/- 14 years) underwent surgery for acute type A aortic dissection. Eighty-six patients with an involvement of the aortic root underwent curative surgery of the proximal aorta consisting of valve-sparing root repair (n = 54, 62.8%) or complete valve and root replacement using composite valve grafts (n = 32, 37.2%). In patients with root repair, all dissected aortic walls were resected and root remodelling using the single patch technique (n = 53) or root repair with valve reimplantation (n = 1) was performed without the use of any glue. All perioperative data were collected prospectively and retrospective statistical examination was performed using univariate and multivariate analyses. RESULTS: The mean follow-up was 5.2 +/- 3.5 years for all patients (range 0-12 years) and 6.1 +/- 3.3 years for survivors. The 30-day mortality rate was 5.8% (5 patients), being considerably lower in the repair sub cohort (1.9 vs 12.5%). The estimated survival rate at 5 and 10 years was 80.0 +/- 4.5 and 69.1 +/- 6.7%, respectively. No patient required reoperation on the proximal aorta and/or aortic valve during the follow-up time and there were only two valve-related events (both embolic, one in each group). Among those patients with repaired valves, the last echocardiography available showed no insufficiency in 40 and an irrelevant insufficiency (1+) in 14. CONCLUSIONS: Curative repair of the proximal aorta in acute dissection involving the root provides favourable operative and long-term outcome with very low risk of aortic complications and/or reoperations, regardless if a valve-sparing procedure or replacement with a valve conduit is used. Valve-sparing surgery is frequently suitable, providing excellent outcome and very high durability. PMID- 26848192 TI - Give me a hand: Differential effects of gesture type in guiding young children's problem-solving. AB - Adults' gestures support children's learning in problem-solving tasks, but gestures may be differentially useful to children of different ages, and different features of gestures may make them more or less useful to children. The current study investigated parents' use of gestures to support their young children (1.5 - 6 years) in a block puzzle task (N = 126 parent-child dyads), and identified patterns in parents' gesture use indicating different gestural strategies. Further, we examined the effect of child age on both the frequency and types of gestures parents used, and on their usefulness to support children's learning. Children attempted to solve the puzzle independently before and after receiving help from their parent; half of the parents were instructed to sit on their hands while they helped. Parents who could use their hands appear to use gestures in three strategies: orienting the child to the task, providing abstract information, and providing embodied information; further, they adapted their gesturing to their child's age and skill level. Younger children elicited more frequent and more proximal gestures from parents. Despite the greater use of gestures with younger children, it was the oldest group (4.5-6.0 years) who were most affected by parents' gestures. The oldest group was positively affected by the total frequency of parents' gestures, and in particular, parents' use of embodying gestures (indexes that touched their referents, representational demonstrations with object in hand, and physically guiding child's hands). Though parents rarely used the embodying strategy with older children, it was this strategy which most enhanced the problem-solving of children 4.5 - 6 years. PMID- 26848193 TI - Impact of Treated Sewage Effluent on the Microbiology of a Small Brook Using Flow Cytometry as a Diagnostic Tool. AB - Flow cytometry was applied to assess the microbiological impact of treated sewage effluent discharge into a small brook carrying surface runoff water. Increases in dissolved organic carbon and soluble reactive phosphorous were accompanied by increases in counts of intact bacteria by up to eightfold. Effluent ingress furthermore resulted in a pronounced shift of bacterial clusters. Whereas brook water upstream of the discharge point was characterised by a bacterial cluster with low nucleic acid (LNA) content, downstream water showed a shift to bacteria with high nucleic acid (HNA) content. Changes in the LNA/HNA ratio were largely maintained along the course of the brook. Results suggest that the LNA/HNA ratio can under certain conditions serve as an indicator of anthropogenic nutrient impact. Measuring impact on this low trophic level might be more sensitive and straightforward than measuring macroindicators. More evidence will however be required to assess the usefulness of LNA/HNA measurements to assess the ecological nutrient status of natural waters and the impact of nutrient pollution. PMID- 26848194 TI - Primary prevention of preeclampsia: myth or reality? PMID- 26848195 TI - Preeclampsia prevention: a case-control study nested in a cohort. AB - BACKGROUND: Preeclampsia is the main complication of pregnancy in developing countries. Calcium starting at 14 weeks of pregnancy is indicated to prevent the disease. Recent advances in prevention of preeclampsia endorse the addition of conjugated linoleic acid. OBJECTIVE: To estimate the protective effect from calcium alone, compared to calcium plus conjugated linoleic acid in nulliparous women at risk of preeclampsia. METHODS: A case-control design nested in the cohort of nulliparous women attending antenatal care from 2010 to 2014. The clinical histories of 387 cases of preeclampsia were compared with 1,054 normotensive controls. The exposure was prescriptions for calcium alone, the first period, or calcium plus conjugated linoleic acid, the second period, from 12 to 16 weeks of gestational age to labor. Confounding variables were controlled, allowing only nulliparous women into the study and stratifying by age, education and ethnic group. RESULTS: The average age was 26.4 yrs old (range= 13-45), 85% from mixed ethnic backgrounds and with high school education. There were no differences between women who received calcium carbonate and those who did not (OR= 0.96; 95% CI= 0.73-1.27). The group of adolescents (13 to 18 years old) in the calcium plus conjugated linoleic acid was protected for preeclampsia (OR= 0.00; 95% CI= 0.00-0.44) independent of the confounder variables. CONCLUSIONS: 1. Calcium supplementation during pregnancy did not have preventive effects on preeclampsia. 2. Calcium plus Conjugated Linoleic acid provided to adolescents was observed to have preventive effect on Preeclampsia. PMID- 26848196 TI - Clinical Aspects associated with Syndromic forms of Orofacial Clefts in a Colombian population. AB - OBJECTIVES: To present descriptive epidemiology of Orofacial Clefts and to determine the association of syndromic forms with antenatal high-risk conditions, preterm birth, and comorbidities among nested-series of cases. METHODS: A study of nested-series of cases was conducted. Frequencies of cleft type, associated congenital anomalies, syndromic, non-syndromic and multiple malformation forms, and distribution of Orofacial Clefts according to sex and affected-side were determined. Odds ratios were calculated as measures of association between syndromic forms and antenatal high-risk conditions, preterm birth and comorbidities. A total of three hundred and eleven patients with Orofacial Clefts were assessed in a 12-month period. RESULTS: The most frequent type of Orofacial Clefts was cleft lip and palate, this type of cleft was more frequent in males, whereas cleft palate occurred more often in females. The most common cases occurred as non-syndromic forms. Aarskog-Scott syndrome showed the highest frequency amongst syndromic forms. Hypertensive disorders in pregnancy, developmental dysplasia of the hip, central nervous diseases and respiratory failure showed significant statistical associations (p <0.05) with syndromic forms. CONCLUSIONS: These data provide an epidemiological reference of Orofacial Clefts in Colombia. Novel associations between syndromic forms and clinical variables are determined. In order to investigate causality relationships between these variables further studies must be carried out. PMID- 26848197 TI - Weaknesses in the reporting of cross-sectional studies according to the STROBE statement: the case of metabolic syndrome in adults from Peru. AB - INTRODUCTION: The inadequate reporting of cross-sectional studies, as in the case of the prevalence of metabolic syndrome, could cause problems in the synthesis of new evidence and lead to errors in the formulation of public policies. OBJECTIVE: To evaluate the reporting quality of the articles regarding metabolic syndrome prevalence in Peruvian adults using the STROBE recommendations. METHODS: We conducted a thorough literature search with the terms "Metabolic Syndrome", "Sindrome Metabolico" and "Peru" in MEDLINE/PubMed, LILACS, SciELO, LIPECS and BVS-Peru until December 2014. We selected those who were population-based observational studies with randomized sampling that reported prevalence of metabolic syndrome in adults aged 18 or more of both sexes. Information was analysed through the STROBE score per item and recommendation. RESULTS: Seventeen articles were included in this study. All articles met the recommendations related to the report of the study's rationale, design, and provision of summary measures. The recommendations with the lowest scores were those related to the sensitivity analysis (8%, n= 1/17), participant flowchart (18%, n= 3/17), missing data analysis (24%, n= 4/17), and number of participants in each study phase (24%, n= 4/17). CONCLUSION: Cross-sectional studies regarding the prevalence of metabolic syndrome in peruvian adults have an inadequate reporting on the methods and results sections. We identified a clear need to improve the quality of such studies. PMID- 26848200 TI - With regard to the reform of the law of medical ethics. PMID- 26848198 TI - Characterization of polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 and relationship to the alcoholism in a Colombian population. AB - OBJECTIVE: Identify and characterize polymorphisms of genes ADH2, ADH3, ALDH2 and CYP2E1 in a Colombian population residing in the city of Bogota and determine its possible relationship to the alcoholism. METHODS: ADH2, ADH3, ALDH2, and CYP2E1 genotypes a population of 148 individuals with non-problematic alcohol and 65 individuals with alcoholism were determined with TaqMan probes and PCR-RFLP. DNA was obtained from peripheral blood white cells. RESULTS: Significant difference was found in family history of alcoholism and use of other psychoactive substances to compare alcoholics with controls. When allelic frequencies for each category (gender) were considered, frequency of A2 allele carriers in ADH2 was found higher in male patients than controls. In women, the relative frequency for c1 allele in CYP2E1 was lower in controls than alcoholics. The ALDH2 locus is monomorphic. No significant differences in allele distributions of the loci examined to compare two populations were observed, however when stratifying the same trend was found that these differences tended to be significant. CONCLUSIONS: This study allows us to conclude the positive association between family history of alcoholism and alcoholism suggesting that there is a favourable hereditary predisposition. Since substance dependence requires interaction of multiple genes, the combination of genotypes ADH2 * 2, CYP2E1 * 1 combined with genotype homozygous ALDH2 * 1 found in this study could be leading to the population to a potential risk to alcoholism. PMID- 26848199 TI - Therapeutic efficacy of alternative primaquine regimens to standard treatment in preventing relapses by Plasmodium vivax: A systematic review and meta-analysis. AB - OBJECTIVE: To compare efficacy and safety of primaquine regimens currently used to prevent relapses by P. vivax. METHODS: A systematic review was carried out to identify clinical trials evaluating efficacy and safety to prevent malaria recurrences by P. vivax of primaquine regimen 0.5 mg/kg/ day for 7 or 14 days compared to standard regimen of 0.25 mg/kg/day for 14 days. Efficacy of primaquine according to cumulative incidence of recurrences after 28 days was determined. The overall relative risk with fixed-effects meta-analysis was estimated. RESULTS: For the regimen 0.5 mg/kg/day/7 days were identified 7 studies, which showed an incidence of recurrence between 0% and 20% with follow up 60-210 days; only 4 studies comparing with the standard regimen 0.25 mg/kg/day/14 days and no difference in recurrences between both regimens (RR= 0.977, 95% CI= 0.670 to 1.423) were found. 3 clinical trials using regimen 0.5 mg/kg/day/14 days with an incidence of recurrences between 1.8% and 18.0% during 330-365 days were identified; only one study comparing with the standard regimen (RR= 0.846, 95% CI= 0.484 to 1.477). High risk of bias and differences in handling of included studies were found. CONCLUSION: Available evidence is insufficient to determine whether currently PQ regimens used as alternative rather than standard treatment have better efficacy and safety in preventing relapse of P. vivax. Clinical trials are required to guide changes in treatment regimen of malaria vivax. PMID- 26848201 TI - Charcot Marie Tooth disease (CMT4A) due to GDAP1 mutation: report of a Colombian family. AB - BACKGROUND: Mutations of GDAP1 gene cause autosomal dominant and autosomal recessive Charcot-Marie-Tooth disease and more than 40 different mutations have been reported. The recessive Q163X mutation has been described in patients of Spanish ancestry, and a founder mutation in South American patients, originating in Spain has been demonstrated. OBJECTIVE: We describe physical and histological features, and the molecular impact of mutation Q163X in a Colombian family. METHODS: We report two female patients, daughters of consanguineous parents, with onset of symptoms within the first two years of life, developing severe functional impairment, without evidence of dysmorphic features, hoarseness or diaphragmatic paralysis. Electrophysiology tests showed a sensory and motor neuropathy with axonal pattern. Sequencing of GDAP1 gene was requested and the study identified a homozygous point mutation (c.487 C>T) in exon 4, resulting in a premature stop codon (p.Q163X). This result confirms the diagnosis of Charcot Marie-Tooth disease, type 4A. RESULTS: The patients were referred to Physical Medicine and Rehabilitation service, in order to be evaluated for ambulation assistance. They have been followed by Pulmonology service, for pulmonary function assessment and diaphragmatic paralysis evaluation. Genetic counseling was offered. The study of the genealogy of the patient, phenotypic features, and electrophysiological findings must be included as valuable tools in the clinical approach of the patient with Charcot-Marie-Tooth disease, in order to define a causative mutation. In patients of South American origin, the presence of GDAP1 gene mutations should be considered, especially the Q163X mutation, as the cause of CMT4A disease. PMID- 26848202 TI - Flexor Digitorum Superficialis and Flexor Digitorum Profundus with separated sheaths: a new normal variation in human. AB - CASE DESCRIPTION: A 25 years old man presented with a laceration on radial side of proximal phalanx of 4(th) finger (zone II flexor) which was due to cut with glass. CLINICAL FINDINGS: The sheaths of Tendons of flexor digitorum superficialis and profundus were not the same and each tendon had a separate sheath. TREATMENT AND OUTCOME: The tendons were reconstructed by modified Kessler sutures, after 15 months the patient had a 30 degrees of extension lag even after physiotherapy courses. CLINICAL RELEVANCE: This is the first reported of such normal variation in human hand tendon anatomy. PMID- 26848203 TI - Laryngeal histoplasmosis: report of the first case in Colombia. PMID- 26848204 TI - Testing and Modeling Dependencies Between a Network and Nodal Attributes. AB - Network analysis is often focused on characterizing the dependencies between network relations and node-level attributes. Potential relationships are typically explored by modeling the network as a function of the nodal attributes or by modeling the attributes as a function of the network. These methods require specification of the exact nature of the association between the network and attributes, reduce the network data to a small number of summary statistics, and are unable provide predictions simultaneously for missing attribute and network information. Existing methods that model the attributes and network jointly also assume the data are fully observed. In this article we introduce a unified approach to analysis that addresses these shortcomings. We use a previously developed latent variable model to obtain a low dimensional representation of the network in terms of node-specific network factors. We introduce a novel testing procedure to determine if dependencies exist between the network factors and attributes as a surrogate for a test of dependence between the network and attributes. We also present a joint model for the network relations and attributes, for use if the hypothesis of independence is rejected, that can capture a variety of dependence patterns and be used to make inference and predictions for missing observations. PMID- 26848205 TI - A High-Dimensional Nonparametric Multivariate Test for Mean Vector. AB - This work is concerned with testing the population mean vector of nonnormal high dimensional multivariate data. Several tests for high-dimensional mean vector, based on modifying the classical Hotelling T2 test, have been proposed in the literature. Despite their usefulness, they tend to have unsatisfactory power performance for heavy-tailed multivariate data, which frequently arise in genomics and quantitative finance. This paper proposes a novel high-dimensional nonparametric test for the population mean vector for a general class of multivariate distributions. With the aid of new tools in modern probability theory, we proved that the limiting null distribution of the proposed test is normal under mild conditions when p is substantially larger than n. We further study the local power of the proposed test and compare its relative efficiency with a modified Hotelling T2 test for high-dimensional data. An interesting finding is that the newly proposed test can have even more substantial power gain with large p than the traditional nonparametric multivariate test does with finite fixed p. We study the finite sample performance of the proposed test via Monte Carlo simulations. We further illustrate its application by an empirical analysis of a genomics data set. PMID- 26848206 TI - A supervoxel-based segmentation method for prostate MR images. AB - Accurate segmentation of the prostate has many applications in prostate cancer diagnosis and therapy. In this paper, we propose a "Supervoxel" based method for prostate segmentation. The prostate segmentation problem is considered as assigning a label to each supervoxel. An energy function with data and smoothness terms is used to model the labeling process. The data term estimates the likelihood of a supervoxel belongs to the prostate according to a shape feature. The geometric relationship between two neighboring supervoxels is used to construct a smoothness term. A three-dimensional (3D) graph cut method is used to minimize the energy function in order to segment the prostate. A 3D level set is then used to get a smooth surface based on the output of the graph cut. The performance of the proposed segmentation algorithm was evaluated with respect to the manual segmentation ground truth. The experimental results on 12 prostate volumes showed that the proposed algorithm yields a mean Dice similarity coefficient of 86.9%+/-3.2%. The segmentation method can be used not only for the prostate but also for other organs. PMID- 26848207 TI - Size Distribution and Estimated Respiratory Deposition of Total Chromium, Hexavalent Chromium, Manganese, and Nickel in Gas Metal Arc Welding Fume Aerosols. AB - A laboratory study was conducted to determine the mass of total Cr, Cr(VI), Mn, and Ni in 15 size fractions for mild and stainless steel gas-metal arc welding (GMAW) fumes. Samples were collected using a nano multi orifice uniform deposition impactor (MOUDI) with polyvinyl chloride filters on each stage. The filters were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography. Limits of detection (LODs) and quantitation (LOQs) were experimentally calculated and percent recoveries were measured from spiked metals in solution and dry, certified welding-fume reference material. The fraction of Cr(VI) in total Cr was estimated by calculating the ratio of Cr(VI) to total Cr mass for each particle size range. Expected, regional deposition of each metal was estimated according to respiratory-deposition models. The weight percent (standard deviation) of Mn in mild steel fumes was 9.2% (6.8%). For stainless steel fumes, the weight percentages were 8.4% (5.4%) for total Cr, 12.2% (6.5%) for Mn, 2.1% (1.5%) for Ni and 0.5% (0.4%) for Cr(VI). All metals presented a fraction between 0.04 and 0.6 MUm. Total Cr and Ni presented an additional fraction <0.03 MUm. On average 6% of the Cr was found in the Cr(VI) valence state. There was no statistical difference between the smallest and largest mean Cr(VI) to total Cr mass ratio (p-value D 0.19), hence our analysis does not show that particle size affects the contribution of Cr(VI) to total Cr. The predicted total respiratory deposition for the metal particles was ~25%. The sites of principal deposition were the head airways (7-10%) and the alveolar region (11 14%). Estimated Cr(VI) deposition was highest in the alveolar region (14%). PMID- 26848208 TI - Perceived discrimination among Latino immigrants in new destinations: The case of Durham, NC. AB - This paper draws on original survey data to assess the prevalence of perceived discrimination among Latin American immigrants to Durham, NC, a "new immigrant destinations" in the Southeastern United States. Even though discrimination has a wide-ranging impact on social groups, from blocked opportunities, to adverse health outcomes, to highlighting and reifying inter-group boundaries, research among immigrant Latinos is rare, especially in new destinations. Our theoretical framework and empirical analysis expand social constructivist approaches that view ethnic discrimination as emerging from processes of competition and incorporation. We broaden prior discussions by investigating the specific social forces that give rise to perceived discrimination. In particular, we examine the extent to which perceptions of unequal treatment vary by gender, elaborating on the situational conditions than differentiate discrimination experiences for men and women. We also incorporate dimensions unique to the contemporary Latino immigrant experience, such as legal status, family migration dynamics, and transnationalism. PMID- 26848210 TI - Extended distally based DMCA flap in combination with autologous amputate skin transplantation as a salvage procedure for ring avulsion injury. AB - : A 23-year-old male student presented to our clinic with a traumatic complex ring avulsion of his right dominant index finger. Clinical evaluation revealed a complete distal amputation of the DIP joint with a laceration of the soft tissue at the middle phalanx and a rupture of the FDP-2-tendon far proximally. We hereby present the patient's clinical outcome after reconstruction with a distally based extended DMCA-II flap. To our own knowledge, this is the first report of an extended distally based DMCA flap for coverage of a class IVd ring avulsion injury in combination with autologous amputate skin transplantation. LEVEL OF EVIDENCE: Level V, therapeutic study. PMID- 26848209 TI - Educating Physical Therapist Students in Tobacco Cessation Counseling: Feasibility and Preliminary Outcomes. AB - BACKGROUND: Smoking is the leading preventable cause of chronic disease and premature morbidity. People with physical disabilities experience elevated smoking prevalence when compared with their non-disabled peers. The physical therapy profession is dedicated to meeting needs of people with physical disabilities, yet most physical therapists (PT) do not typically provide tobacco cessation interventions. Similar deficits exist among other health professions, creating a demand for improved services to address smoking-related health burdens. Within other health professions, insufficient tobacco cessation counseling (TCC) education has been linked to a lack of interventions and may account for similar deficits in physical therapy practice. STUDY PURPOSE: Goals were to assess feasibility, implementation, and results of a tailored TCC educational program for entry-level physical therapist (PT) students. SUBJECTS: Two cohorts of entry-level physical therapist (PT) students (n = 12 and n = 17). METHODS: Educational objectives were established based on prior review of the literature, a survey of national PT education programs, and clinical guidelines for TCC established by the United States Public Health Service (USPHS). Based on these objectives, the team designed a 3-hour workshop involving didactic content and problem-based skills practice. A pre- and post-test survey was used to measure 6 dimensions: knowledge, perceived barriers, perceived facilitators, self efficacy, outcome expectations, and self-rated skill in TCC. Within each cohort, changes in score were compared using a paired t test. The ability to apply clinical guidelines for TCC was assessed using case scenarios and structured observation. These outcomes were selected based on the Theory of Reasoned Action, which states that future behavior is determined by intention to act. Intention to act is a product of knowledge, a positive balance between perceived barriers and facilitators, strong self-efficacy, favorable outcome expectations, and necessary skills. Student satisfaction with training was assessed through anonymous written feedback. Feasibility was based on cost analysis, including material resources, as well as faculty time and effort. RESULTS: Following participation, both cohorts improved in knowledge, perceived facilitators, outcome expectations, and self-rated skill. Cohort 2 also showed an increase in self-efficacy (P < .01). Structured observation revealed competencies in application of clinical guidelines for case-based scenarios. Mean student satisfaction ratings for the educational experience were 5/5, and cost-estimate for delivery of the 3-hour educational intervention was approximately $32 per student. CONCLUSIONS: This research study demonstrated feasibility and impact of an evidence-based curricular model designed to increase likelihood of TCC by future PTs by enhancing factors known to promote TCC behaviors. The program was well-received by students, and objectives were achieved through efficient use of faculty time and resources. Subsequent research should examine the effects of training on the provision of TCC within clinical settings, as well as the impact of TCC on smoking quit rates for patients who have received this intervention as a component of their physical therapy plan of care. PMID- 26848211 TI - Emotion Socialization in the Context of Risk and Psychopathology: Maternal Emotion Coaching Predicts Better Treatment Outcomes for Emotionally Labile Children with Oppositional Defiant Disorder. AB - We examined whether maternal emotion coaching at pre-treatment predicted children's treatment response following a 12-week program addressing children's Oppositional Defiant Disorder (ODD) symptoms. Eighty-nine mother-child dyads participated. At pre-treatment, mothers and children engaged in an emotion talk task. Mothers also reported their beliefs about emotions at pre-treatment and their child's disruptive behavior symptoms, emotion regulation, and emotion lability/negativity at pre-, mid-, and post-treatment. Clinicians reported children's symptom severity at pre- and post-treatment. Children's emotion lability/negativity moderated effects of maternal emotion coaching on children's post-treatment ODD symptoms, with stronger benefits of emotion coaching for children high in emotion lability/negativity. Results suggest that emotion coaching may promote treatment response for children with ODD who are especially at risk due to their emotionality. PMID- 26848212 TI - Current Status of Atopic Dermatitis-Related Information Available on the Internet in South Korea. AB - BACKGROUND: Patients with atopic dermatitis (AD) often resort to the internet for disease-related information. We believe that dermatologists be informed about the current accessibility of information to patients and the potential for misleading patients into making poor treatment decisions. OBJECTIVE: The study was carried out in order to determine the nature of AD-related information available on the internet in Korea, and to identify any changes since our last survey in 2005. The quality of information offered and the involvement of medical doctors in certain websites were also investigated. METHODS: Taking into account the current search engine market share in Korea, we gathered all search results obtained from the three major search engines using the keyword 'atopy', and investigated the nature of the information retrieved. RESULTS: The search results showed less commercial sites than our previous study in 2005. There is a dramatic increase in the number of public bodies offering information about AD. In addition, the quality of information available online has improved since our last survey. CONCLUSION: The phenomenon of 'commercial overcrowding' seems to have stabilized. As AD becomes a more social phenomenon, patients are better informed than ever before. However, the information available on the internet still requires to be accompanied by consultation by dermatologists. We believe that self-regulation using a format such as the Health on the Net Foundation's code of conduct (HONcode) may improve the quality of online information accessible to patients with AD in Korea. PMID- 26848213 TI - Quality of Life and Economic Burden in Recessive Dystrophic Epidermolysis Bullosa. AB - BACKGROUND: Patients with recessive dystrophic epidermolysis bullosa (RDEB) exhibit blisters and erosions since birth, causing pain, pruritus and various complications. RDEB affects quality of life (QoL) in physical, emotional and social aspects. Furthermore, interminable dressing changes and supportive therapies impose a significant economic burden on the patient's family. OBJECTIVE: We assessed the QoL and economic burden in patients with RDEB. METHODS: Sixteen patients with RDEB were surveyed to assess the QoL and economic burden. Patients answered questionnaires consisting of a visual analogue scale (VAS) on pain and pruritus, Skindex-29, Quality of Life in EB questionnaire (QOLEB), and the economic burden due to EB. RESULTS: Thirteen patients with RDEB completed the questionnaire. Female patients presented higher VAS, QOLEB and total Skindex-29 scores than male patients. Patients with RDEB showed severe levels of pruritus, which was more intolerable than pain. Mean VAS score on pain in RDEB was higher than in oral lichen planus and post-herpetic neuralgia. VAS score on pruritus was similar to those in chronic urticaria, atopic dermatitis, and prurigo nodularis. Compared with other dermatologic conditions, patients with RDEB were profoundly affected in all three scales of skindex-29. Mean "medical cost" in a month was $257.54 (USD) (+/-169.39) and mean "dressing cost" was $358.41 (USD) (+/-312.55), which was negatively related to patient age. CONCLUSION: RDEB had a profound impact on QoL and economic burden. Compared with other dermatologic diseases, RDEB showed severe symptoms and QoL was seriously impaired. Most patients sustained economic burdens, especially on preparing dressing materials. Younger patients experienced more economic burdens. PMID- 26848214 TI - Enhancement of Human Hair Growth Using Ecklonia cava Polyphenols. AB - BACKGROUND: Ecklonia cava is a brown alga that contains various compounds, including carotenoids, fucoidans, and phlorotannins. E. cava polyphenols (ECPs) are known to increase fibroblast survival. The human dermal papilla cell (hDPC) has the properties of mesenchymal-origin fibroblasts. OBJECTIVE: This study aims to investigate the effect of ECPs on human hair growth promotion in vitro and ex vivo. METHODS: MTT assays were conducted to examine the effect of ECPs on hDPC proliferation. Hair growth was measured using ex-vivo hair follicle cultures. Real-time polymerase chain reaction was performed to evaluate the mRNA expression of various growth factors in ECP-treated hDPCs. RESULTS: Treatment with 10 ug/ml purified polyphenols from E. cava (PPE) enhanced the proliferation of hDPCs 30.3% more than in the negative control (p<0.001). Furthermore, 0.1 ug/ml PPE extended the human hair shaft 30.8% longer than the negative control over 9 days (p<0.05). Insulin-like growth factor-1 (IGF-1) mRNA expression increased 3.2-fold in hDPCs following treatment with 6 ug/ml PPE (p<0.05). Vascular endothelial growth factor (VEGF) mRNA expression was also increased 2.0-fold by 3 ug/ml PPE (p<0.05). Treatment with 10 ug/ml PPE reduced oxidative stress in hDPCs (p<0.05). CONCLUSION: These results suggest that PPE could enhance human hair growth. This can be explained by hDPC proliferation coupled with increases in growth factors such as IGF-1 and VEGF. Reducing oxidative stress is also thought to help increase hDPCs. These favorable results suggest that PPE is a promising therapeutic candidate for hair loss. PMID- 26848215 TI - Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model. AB - BACKGROUND: Many inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation. However, the endogenous modulators for mast cell activation and the underlying mechanism have yet to be elucidated. Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation. OBJECTIVE: In order to investigate the effect of cannabinoid receptor-1 (CB1R) agonists on mast cell activation, AEA-derived compounds were newly synthesized and evaluated for their effect on mast cell activation. METHODS: The effects of selected compounds on FcepsilonRI-induced histamine and beta-hexosaminidase release were evaluated in a rat basophilic leukemia cell line (RBL-2H3). To further investigate the inhibitory effects of CB1R agonist in vivo, an oxazolone-induced atopic dermatitis mouse model was exploited. RESULTS: We found that CB1R inhibited the release of inflammatory mediators without causing cytotoxicity in RBL-2H3 cells and that CB1R agonists markedly and dose-dependently suppressed mast cell proliferation indicating that CB1R plays an important role in modulating antigen dependent immunoglobulin E (IgE)-mediated mast cell activation. We also found that topical application of CB1R agonists suppressed the recruitment of mast cells into the skin and reduced the level of blood histamine. CONCLUSION: Our results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis. PMID- 26848216 TI - Genetic Risk Factors for Psoriasis in Turkish Population: -1540 C/A, -1512 Ins18, and +405 C/G Polymorphisms within the Vascular Endothelial Growth Factor Gene. AB - BACKGROUND: Evidence regarding the vascular endothelial growth factor A (VEGFA) as a potent mediator of angiogenesis and inflammation in psoriasis has revealed variations in this gene as surrogate markers of psoriasis. OBJECTIVE: VEGFA gene polymorphisms (-1540 C/A, -1512 Ins18, -460 T/C, and +405 C/G) in psoriasis susceptibility in Turkish population were investigated. METHODS: A total of 200 age, sex and ethnicity-matched psoriatic and healthy individuals were examined for clinical type, response to therapy, serum VEGFA and its receptor levels, genotypes and haplotypes. RESULTS: The +405 GG, +405 CG, -1540 CA, and -1512 +Ins18 genotypes conferred a significant risk for developing psoriasis. The C InsTC haplotype in the controls and C+InsTG, A+InsTC, and A-InsTG haplotypes in psoriatic patients were observed to be significantly high. Increased serum levels of VEGFA were detected in psoriatic patients with the C-InsTC haplotype than that in the controls. The +405 GG genotype was significantly more frequent in psoriatic patients with a positive family history, and the moderate form of psoriasis was more frequent among C+InsTG haplotype carriers than that among the other patients. The +405 GG genotype was found to be more frequent in patients responding to oral retinoids. Serum VEGFR1/FLT1 and VEGFR2/KDR levels were not significantly different when psoriatic patients and controls were stratified based on the risk polymorphic variants. CONCLUSION: VEGFA gene +405 GG and CG, 1512+Ins18, and -1540 CA genotypes are associated with an increased risk of psoriasis in Turkish population. The G allele at +405 and an 18-bp insertion at 1512 are primarily the risk factors for psoriasis, and this risk is potentiated by the presence of the A allele at the -1540 locus. PMID- 26848217 TI - Dermatoses of the Glans Penis in Korea: A 10-Year Single Center Experience. AB - BACKGROUND: A variety of infectious, inflammatory, and neoplastic dermatoses can develop on the glans penis, and definitive diagnosis in such cases may be difficult owing to their non-specific symptoms and clinical appearance. Furthermore, data on dermatoses of the glans penis in Korea are limited. OBJECTIVE: In the present study, we aimed to determine the prevalence of dermatoses of the glans penis in Korea and provide clinical data to assist in making an accurate diagnosis. METHODS: We retrospectively reviewed the medical records, clinical photographs, and histologic slides of 65 patients with dermatoses of the glans penis that visited the Pusan National University Hospital between January 2004 and August 2013. RESULTS: Twenty-six types of dermatoses were identified: inflammatory dermatosis was the most common (38/65, 58.5%), followed by infectious (13/65, 20.0%), neoplastic (10/65, 15.4%), and other dermatoses (4/65, 6.2%). The most common dermatosis of the glans penis was seborrheic dermatitis, followed by lichen planus, herpes progenitalis, condyloma accuminatum, erythroplasia of Queyrat, Zoon's balanitis, and psoriasis. In the topographic analysis, the most common type of dermatosis was dermatoses that localized to the glans penis (39/65, 60.0%), followed by dermatoses involving the extra-genitalia and glans penis (22/65, 33.9%), and the genitalia (glans penis plus other genital areas) (4/65, 6.2%). CONCLUSION: This study shows the usefulness of a topographic approach in the diagnosis of dermatoses of the glans penis in Korea. The findings could be used as baseline data for establishing an accurate diagnosis in Koreans. PMID- 26848218 TI - Interaction of Wnt5a with Notch1 is Critical for the Pathogenesis of Psoriasis. AB - BACKGROUND: Psoriasis is characterized by uncontrolled hyperproliferation, aberrant differentiation, and dermal infiltration of immune cells. Recent studies have reported that Wnt5a and Notch1 signaling are altered in psoriatic skin lesions. OBJECTIVE: We aimed to investigate the interaction of Wnt5a with Notch 1 with respect to inflammation-mediated epidermal hyperproliferation in psoriasis. METHODS: Expression of Wnt5a and Notch1 signaling-related proteins were examined in psoriatic skin biopsies. Wnt5a was upregulated in human keratinocytes by treating the cells with its recombinant form (rWnt5a). RESULTS: In psoriatic lesions, expression of Wnt5a increased while that of Notch1 decreased when compared to that in non-lesional and normal skin. Treatment with rWnt5a increased the proliferation of keratinocytes and increased their secretion of interleukin (IL)-23, IL-12, and tumor necrosis factor (TNF)-alpha. Further, exposure of keratinocytes to IL-1alpha, TNF-alpha, transforming growth factor-alpha, and interferon-gamma downregulated Notch1 as well as HES 1, which is downstream to Notch1, but increased the Wnt5a levels. The upregulated Wnt5a in keratinocytes downregulated both Notch1 and HES1. CONCLUSION: Our data suggest that Wnt5a and Notch1 signaling exert counteracting influences on each other and are involved, in part, in the pathomechanism of psoriasis. PMID- 26848219 TI - Role of Arachidonic Acid in Promoting Hair Growth. AB - BACKGROUND: Arachidonic acid (AA) is an omega-6 polyunsaturated fatty acid present in all mammalian cell membranes, and involved in the regulation of many cellular processes, including cell survival, angiogenesis, and mitogenesis. The dermal papilla, composed of specialized fibroblasts located in the bulb of the hair follicle, contributes to the control of hair growth and the hair cycle. OBJECTIVE: This study investigated the effect of AA on hair growth by using in vivo and in vitro models. METHODS: The effect of AA on human dermal papilla cells (hDPCs) and hair shaft elongation was evaluated by MTT assay and hair follicle organ culture, respectively. The expression of various growth and survival factors in hDPCs were investigated by western blot or immunohistochemistry. The ability of AA to induce and prolong anagen phase in C57BL/6 mice was analyzed. RESULTS: AA was found to enhance the viability of hDPCs and promote the expression of several factors responsible for hair growth, including fibroblast growth factor-7 (FGF-7) and FGF-10. Western blotting identified the role of AA in the phosphorylation of various transcription factors (ERK, CREB, and AKT) and increased expression of Bcl-2 in hDPCs. In addition, AA significantly promoted hair shaft elongation, with increased proliferation of matrix keratinocytes, during ex vivo hair follicle culture. It was also found to promote hair growth by induction and prolongation of anagen phase in telogen-stage C57BL/6 mice. CONCLUSION: This study concludes that AA plays a role in promoting hair growth by increasing the expression of growth factors in hDPCs and enhancing follicle proliferation and survival. PMID- 26848220 TI - Topical Products for Human Hair Regeneration: A Comparative Study on an Animal Model. AB - BACKGROUND: Hair loss and hair growth is the subject of tremendous amount of research. OBJECTIVE: This study investigated the efficacy of three chemical treatments used in humans for hair loss, using a rat model of hair regrowth. The products tested were 2% minoxidil, Hairgrow (Dar-Al-Dawa Pharma), Aminexil, Dercos (Vichy Laboratoires), and Kerium, Anti-chute (La Roche-Posay). METHODS: Thirty-two adult female Wistar-Bratislava rats were assigned to 4 groups. Two rectangular areas (2*4 cm) were shaved on either sides of the mid dorsal line (left side - control; right side - test area). Group I was treated topically with 2% minoxidil, group II with Aminexil, and group III with Kerium. Each rat received 0.3 ml of substance applied topically to the shaved dorsal skin every day for 28 days. Rats in group IV served as sham controls receiving no treatment. Hair regrowth was evaluated by trichoscopy (with a dermatoscope), grown hair weight (from a surface area of 1 cm(2)), and histopathological examination for skin thickness, follicle count, and percentage of anagen induction (morphometric assessment). RESULTS: Treatment with 2% minoxidil significantly induced hair regrowth as assessed by trichoscopy, hair weight examination, and morphometric evaluation. Hair weight examination and morphometric assessment demonstrated the lowest hair growth effect with Aminexil among the tested products. Treatment with Kerium was found to significantly induce hair regrowth (p<0.05 as compared to the control group). CONCLUSION: Our study demonstrates that hair regrowth efficacy of products recommended for human use is not similar when tested on an animal model. PMID- 26848221 TI - Association of Adipokines, Insulin Resistance, Hypertension and Dyslipidemia in Patients with Psoriasis Vulgaris. AB - BACKGROUND: Systemic inflammation in psoriasis causes insulin resistance and cardiovascular diseases. Adipokines are adipose-tissue-derived factors that are involved in metabolic processes. It is thought that these adipokines are associated with the development of psoriasis. OBJECTIVE: The purpose of this study was to determine the changes in adipokine levels, insulin resistance, hypertension, and dyslipidemia over a 12-week period. METHODS: The study comprised 35 psoriasis patients and 50 controls. Blood samples were obtained twice from the patients, one sample at the start and one at the end of a 12-week follow-up period. The following parameters were assessed in both groups: serum fasting glucose, fasting insulin, homeostasis model assessment-estimated insulin resistance (HOMA-IR) index, serum lipids, adiponectin, leptin, resistin, chemerin, omentin, vaspin, visfatin, retinol-binding protein 4, and high sensitivity C-reactive protein (hs-CRP) levels; blood pressure; body mass index; and the psoriasis area severity index (PASI) scores. RESULTS: The patients showed an improvement in the PASI score and a significant decrease in serum hs-CRP, omentin, and chemerin values. Moreover, at the start of the follow-up, the psoriasis patients had significantly lower levels of adiponectin and visfatin and significantly higher levels of vaspin and resistin than those of the control group. Visfatin levels correlated negatively with low-density lipoprotein (LDL) and cholesterol, while vaspin and omentin levels correlated positively with diastolic blood pressure. Decreased adiponectin levels correlated negatively with diastolic blood pressure and LDL. CONCLUSION: Plasma levels of adipokines might be useful for evaluating the disease activity of psoriasis and its comorbidities. PMID- 26848222 TI - Avoidance Behavior against Positive Allergens Detected with a Multiple Allergen Simultaneous Test Immunoblot Assay in Patients with Urticaria: Factors Associated with Avoidance Success/Failure. AB - BACKGROUND: Avoidance behavior against positive allergens detected by using multiple allergen simultaneous test (MAST)-immunoblot assay in patients with urticaria has been rarely reported. OBJECTIVE: We aimed to assess the avoidance behavior of patients with urticaria against positive allergens detected with a MAST. METHODS: One hundred and one urticaria patients who showed positivity to at least one allergen on a MAST completed a questionnaire regarding their test results. The avoidance behavior of the patients was evaluated, and relevant determining factors of avoidance success/failure were statistically assessed. RESULTS: We detected 144 different data (n=51, food allergens; n=17, pollen allergens; and n=76, aeroallergens) from 101 patients with urticaria. The avoidance failure rates were 33.3% for food allergens, 70.6% for pollen allergens, and 30.3% for aeroallergens. The pollen group showed a significantly higher avoidance failure rate than the food and aeroallergen groups (p<0.05). The patients with higher educational levels or more severe urticaria tended to successfully avoid allergens (p<0.05). The monthly household income level and patients' reliability to the test showed borderline correlations (p=0.057 and p=0.075, respectively). CONCLUSION: We believe that the results of this study could be helpful in predicting avoidance success or failure against allergens in patients with urticaria when clinicians conduct allergen-specific immunoglobulin E tests. PMID- 26848223 TI - Considerable Variability in the Efficacy of 8% Capsaicin Topical Patches in the Treatment of Chronic Pruritus in 3 Patients with Notalgia Paresthetica. AB - Notalgia paresthetica (NP) is a focal neuropathic itch condition manifesting in intense chronic or recurrent episodic itch in a hyperpigmented, macular, uni- or bilateral skin area located below and/or medially to the scapulae. Achieving satisfactory relieve in NP patients is challenging. In this case-series three female NP patients were treated with 8% capsaicin patches following a spatial quantification of their alloknetic area with a von Frey filament. The use of a von Frey filament in order to delimit the precise area of itch sensitization and thus patch application, proved clinically feasible. Although 8% topical capsaicin relieved itch in all three patients, the duration of the effectiveness varied greatly from only 3 days to >2 months. The treatment was well tolerated in the patients and there appear to be no significant hindrances to applying this treatment with NP as an indication, although it may only exhibit satisfactory effectiveness in certain patients. Placebo-controlled double-blinded trials are needed to confirm the effectiveness of the treatment and assess predictive parameters of the treatment outcome. PMID- 26848224 TI - Chronic Graft-Versus-Host Disease Mimicking Psoriasis in a Patient with Hemophagocytic Lymphohistiocytosis. AB - Graft-versus-host disease (GVHD) is a common complication of bone marrow transplantation (BMT) that can be classified as acute or chronic. Chronic GVHD, which usually occurs more than 3 months after BMT, includes typical lichenoid or sclerodermatous lesions. Psoriasiform eruption is a rare clinical manifestation of chronic GVHD, and there have been no reports of psoriasiform chronic GVHD associated with hemophagocytic lymphohistiocytosis. A 33-year-old woman who was diagnosed with hemophagocytic lymphohistiocytosis 10 years ago visited our outpatient clinic with psoriasiform eruption over her entire body. She underwent allogeneic BMT 7 months previously from her sibling. Skin biopsy was performed on the lesion, and the histological features suggested GVHD. The psoriasiform lesions improved with narrow-band ultraviolet B phototherapy, with secondary vitiligo remaining on the corresponding locations. PMID- 26848226 TI - Piperacillin/Tazobactam-Associated Hypersensitivity Syndrome with Overlapping Features of Acute Generalized Exanthematous Pustulosis and Drug-Related Rash with Eosinophilia and Systemic Symptoms Syndrome. AB - Acute generalized exanthematous pustulosis (AGEP) is a rare disorder characterized by acute onset of erythematous and edematous eruptions with sterile pustules, accompanied by fever, and a self-limiting condition thought to be caused by drugs, in particular, antibiotics. Drug-related rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug-induced reaction, characterized by a generalized skin rash associated with hypereosinophilia, lymphocytosis, and internal organ involvement. These reactions differ in causative agents, as well as clinical presentation, prognosis, and treatment. Therefore, appropriate diagnostic measures should be rapidly undertaken. Herein, we described a patient who developed overlapping features of hypersensitivity syndromes, AGEP and DRESS, with the use of piperacillin and the beta-lactamase inhibitor sodium tazobactam. Coexistence of AGEP and DRESS in the same patient is quite rare. To the best of our knowledge, there have been no previous reports on the coexistence of AGEP and DRESS associated with piperacillin/tazobactam. PMID- 26848225 TI - Severe Nail Fold Psoriasis Extending from Nail Psoriasis Resolved with Ustekinumab: Suggestion of a Cytokine Overflow Theory in the Nail Unit. AB - Because nail psoriasis is difficult to treat, therapy with many biological drugs has been attempted. Ustekinumab is approved for chronic plaque psoriasis and psoriatic arthritis (PsA), with some trials reporting nail improvement using this agent. A 51-year-old man with severe chronic plaque psoriasis had severe involvement of all fingernails and toenails, with accompanying nail fold psoriasis. He also had PsA of the small joints of the fingers. Despite multiple conventional therapies, the nail lesions did not improve, and his nail psoriasis severity index score was 97. After a fourth ustekinumab injection, most of the fingernail psoriasis was resolved, and only hyperkeratosis remained on both large toenails. Because the nail plate, nail fold, and small joints of the fingers are closely apposed structures within a small area, cytokines produced from the nail units overflow to the nail fold and small joints and can induce nail fold psoriasis and PsA. PMID- 26848227 TI - A Case of Pemphigus Herpetiformis with Only Immunoglobulin G Anti-Desmocollin 3 Antibodies. AB - Pemphigus represents a group of autoimmune blistering diseases caused by autoantibodies against desmogleins (Dsgs), a class of desmosomal cadherins. Recently, several pemphigus patients only with desmocollin (Dsc) 3-specific antibodies have been reported. Here, we report a case of pemphigus herpetiformis (PH), where only anti-Dsc3-specific antibodies but not anti-Dsg antibodies were detected. A 76-year-old woman presented with a 3-year history of blister formation. Physical examination revealed pruritic erythemas with vesicles on the trunk and legs, but no lesions of the oral mucosa. A skin biopsy specimen revealed intraepidermal blister containing neutrophils, eosinophils, and lymphocytes. Direct immunofluorescence (IF) showed immunoglobulin G (IgG) and complement 3 (C3) depositions on the keratinocyte cell surfaces. Indirect IF showed IgG anti-keratinocyte cell surface antibodies. These findings hinted at a diagnosis of pemphigus. However, repeated enzyme-linked immunosorbent assays (ELISAs) for both anti-Dsg1 and 3 antibodies proved to be negative. Immunoblotting of normal human epidermal extracts revealed Dsc antibodies, and recently established ELISAs using human Dsc1-Dsc3 recombinantly expressed in mammalian cells detected anti-Dsc3 antibodies. Based on these clinical, histopathological, and immunological findings, the patient was diagnosed as PH with only anti-Dsc3 antibodies. Treatment with corticosteroid prednisolone and steroid-sparing agent dapsone accomplished complete clinical remission of the patient. PMID- 26848228 TI - Efficacy and Safety of Hyaluronic Acid with and without Radiofrequency for Forehead Augmentation: A Pilot Study Using Three-Dimensional Imaging Analysis. PMID- 26848229 TI - Evaluation of the Potential Association between NOS Gene Polymorphisms (iNOS G 954C and eNOS G894T) and Psoriasis. PMID- 26848230 TI - Treatment of Classic Kaposi's Sarcoma Showing a Discretely Scattered Distribution with Intralesional Vinblastine Injections. PMID- 26848231 TI - Increasing Numbers of Mast Cells in Skin Lesions of Hyperpigmented Mycosis Fungoides with Large-Cell Transformation. PMID- 26848232 TI - Stevens-Johnson Syndrome-Like Skin Lesions in a Patient with Juvenile Systemic Lupus Erythematosus. PMID- 26848233 TI - A Case of Acute-Onset, Painful Acral Granuloma Annulare. PMID- 26848234 TI - Erythrodermic Psoriasis Improved by Ustekinumab: A Report of Two Cases. PMID- 26848235 TI - Congenital Melanocytic Nevus with Distinctive Nevus Cell Proliferation within Multiple Epidermal Cyst-Like Changes. PMID- 26848236 TI - Treatment for Refractory Pruritus Using Oral Aprepitant. PMID- 26848237 TI - Acidic Water Bathing Could Be a Safe and Effective Therapeutic Modality for Severe and Refractory Atopic Dermatitis. PMID- 26848238 TI - Effects of Magnesium Ascorbyl Phosphate on the Expression of Inflammatory Biomarkers after Treatment of Cultured Sebocytes with Propionibacterium acnes or Ultraviolet B Radiation. PMID- 26848239 TI - Pathogenesis of Plantar Epidermal Cyst: Three-Dimensional Reconstruction Analysis. PMID- 26848241 TI - Secondary Granulomatous Cutaneous Involvement in Peripheral T-cell Lymphoma. PMID- 26848240 TI - Eruptive Xanthoma with Acute Pancreatitis in a Patient with Hypertriglyceridemia and Diabetes. PMID- 26848243 TI - Extensive Squamous Cell Carcinoma Originating from a Burn Scar: Marjolin's Ulcer with an Unusual Presentation. PMID- 26848242 TI - Single Vesicular Papule on the Eyelid with Atypical Histopathology Findings. PMID- 26848245 TI - Kristen's Birth Story. AB - Kristen shares the story of the birth of her son. She had a rapid labor and was not sure, because she was moving so quickly, that she could have the natural birth she planned. After a wait in triage, Kristen, with the support of her husband and mother, and with the encouragement, support, and protection of her midwife, gave birth to her son. PMID- 26848244 TI - The Usefulness of Dermoscopy for Detection of Subungual White Foreign Bodies. PMID- 26848246 TI - Theorists and Techniques: Connecting Education Theories to Lamaze Teaching Techniques. AB - Should childbirth educators connect education theory to technique? Is there more to learning about theorists than memorizing facts for an assessment? Are childbirth educators uniquely poised to glean wisdom from theorists and enhance their classes with interactive techniques inspiring participant knowledge and empowerment? Yes, yes, and yes. This article will explore how an awareness of education theory can enhance retention of material through interactive learning techniques. Lamaze International childbirth classes already prepare participants for the childbearing year by using positive group dynamics; theory will empower childbirth educators to address education through well-studied avenues. Childbirth educators can provide evidence-based learning techniques in their classes and create true behavioral change. PMID- 26848247 TI - Mother's Beliefs, Attitudes, and Decision Making Related to Infant Feeding Choices. AB - All mothers at some point make a decision about whether to breast- or formula feed their infant. Marital status, education, age, culture, and confidence have all been identified as variables affecting this decision. Previous research has concentrated on the decision-making process in breastfeeding mothers. This qualitative descriptive study investigated the beliefs, attitudes, and decisions of both breast- and formula-feeding mothers. Four categories were identified influencing maternal decision making: (a) infant nutritional benefits, (b) maternal benefits, (c) knowledge about infant feeding, and (d) personal and professional support. Analysis of the data indicated that mothers differed in their choice depending on whether they were infant- or maternal-centered and that most women combine both methods of feeding. PMID- 26848248 TI - Access, Use, and Preferences for Technology-Based Perinatal and Breastfeeding Support Among Childbearing Women. AB - We surveyed 146 postpartum women who birthed at 34-37 6/7 weeks of gestation and intended to breastfeed about their use of and preferences regarding technology to obtain perinatal and breastfeeding support. Most participants owned smartphones and used technology during pregnancy to track pregnancy data, follow fetal development, address pregnancy concerns, and obtain breastfeeding information. Internet, e-mail, apps, and multiplatform resources were the most popular technologies used and preferred. Demographic differences existed in mobile technology access and preferences for different technologies. In terms of technology-based breastfeeding support, women wanted encouragement, anticipatory guidance, and information about milk production. A nuanced understanding of the technology childbearing women use and desire has the potential to impact clinical care and inform perinatal support interventions. PMID- 26848249 TI - Uncovering the Golden Veil: Applying the Evidence for Telephone Screening to Detect Early Postpartum Depression. AB - Postpartum depression (PPD) is often detected later than symptom onset, or even undetected, because of lack of prompt or adequate screening. An evidence-based PPD screening protocol using a telephone-based format within a primary care practice was developed to identify symptoms and initiate treatment between 2 and 3 weeks postpartum. The Edinburgh Postnatal Depression Scale was used, with positive screens referred for provider and support services, and then tracked for follow-through. Fifty-two percent of women screened positive. Sixty-four percent accepted both provider and support referrals, with 89% follow-through with provider referrals and 78% follow-through with support referrals. Outcomes support early screening for PPD using a telephone-based format to effectively identify symptoms and acceptance of referrals by participants. PMID- 26848250 TI - Understanding Factors That Influence Adolescent Mothers' Doula Use: A Qualitative Study. AB - In this study, we examined factors that influenced doula use among adolescent mothers in a community-based childbirth education and doula program. We used a qualitative case study approach to gather perspectives from adolescent mothers and doulas through semistructured interviews, field observations, and a focus group. These women collectively revealed multiple themes related to doula use among adolescent mothers, including relationship development and barriers to doula use at the individual and structural levels. Effective training and support for doulas that serve adolescent clients can improve these mothers' birth experiences, and program planners in the United States and other countries can use process evaluations to improve doula programs for adolescent mothers. PMID- 26848251 TI - Becoming a Mother and Learning to Breastfeed: An Emergent Autoethnography. AB - A woman's journey into motherhood and first encounters with breastfeeding are profound learning experiences. During the perinatal period of my first pregnancy, I kept a journal documenting my thoughts and feelings. What emerged from my journals is an autoethnography, revealing my new understandings of myself as a woman within a culture of mothers and a deeper understanding of myself as a learner. Anecdotal stories shared with me by other women became the impetus for my reflection during my journey into motherhood. Although learning to breastfeed for the first time, I became aware of the significance of lived experience on my learning. As I interweave my personal and scholarly voices, I present to you my journals layered with my research. PMID- 26848253 TI - Current recommendations for laboratory-based screening tests for older men. PMID- 26848252 TI - Effects of Deep Brain Stimulation on Pausing During Spontaneous Speech in Parkinson's Disease. AB - The present study examined pausing patterns in spontaneous speech as a measure of the effect of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on parkinsonian speech. Pauses reflect various aspects of speech and language processes, including motor initiation and linguistic planning. Relatively little attention has been given to pauses in determining the effect of STN-DBS. An examination of pausing may be helpful to understanding how this form of therapy affects these behaviors. Seven individuals with Parkinson's disease who received surgery for bilateral STN-DBS participated. Spontaneous speech samples were elicited in both the ON and OFF STN-DBS condition. Findings indicated that long pauses (250-3000 ms) in spontaneous speech were significantly shorter and more frequent in the STN-DBS ON condition. Furthermore, the proportion of nonlinguistic boundary pauses was significantly greater with stimulation. The findings support previous studies suggesting that speech motor control and lexical retrieval may be affected by STN-DBS. PMID- 26848254 TI - Recommendations for lab-based screening tests for adult women. PMID- 26848255 TI - NABIC: A New Access Portal to Search, Visualize, and Share Agricultural Genomics Data. AB - The National Agricultural Biotechnology Information Center developed an access portal to search, visualize, and share agricultural genomics data with a focus on South Korean information and resources. The portal features an agricultural biotechnology database containing a wide range of omics data from public and proprietary sources. We collected 28.4 TB of data from 162 agricultural organisms, with 10 types of omics data comprising next-generation sequencing sequence read archive, genome, gene, nucleotide, DNA chip, expressed sequence tag, interactome, protein structure, molecular marker, and single-nucleotide polymorphism datasets. Our genomic resources contain information on five animals, seven plants, and one fungus, which is accessed through a genome browser. We also developed a data submission and analysis system as a web service, with easy-to use functions and cutting-edge algorithms, including those for handling next generation sequencing data. PMID- 26848256 TI - Isolation of Circulating Tumor Cells from Multiple Epithelial Cancers with ApoStream((r)) for Detecting (or Monitoring) the Expression of Folate Receptor Alpha. AB - This study describes our efforts to further the field of noninvasive diagnostics, specifically in the area of liquid biopsies in oncology. We employed laser scanning cytometry using highly selective antibodies to interrogate circulating tumor cells (CTCs) that were isolated using ApoStream((r)) technology to identify folate receptor alpha (FRalpha)-positive cells. We demonstrate that FRalpha(+) CTCs can be isolated from patients with metastatic cancers, including NSCLC adenocarcinoma, breast cancer, and ovarian cancer, whereas squamous cell lung cancer and normal healthy controls were devoid of FRalpha(+) CTCs. We believe that the developed methodology will have applications in both the diagnosis and the monitoring of FRalpha-expressing cancers. Folate receptor alpha (FRalpha) expression may have utility as a potential diagnostic and therapeutic target in solid tumors. As tissue samples are not always available for patient screening, this study evaluated a noninvasive assay in CTCs from blood samples to detect FRalpha expression. The presence of FRalpha(+) CTCs enriched using ApoStream((r)) and detected using laser capture cytometry was evaluated in blood samples from cancer patients [NSCLC adenocarcinoma (n = 14), breast cancer (n = 20), ovarian cancer (n = 6), and squamous lung cancer patients (n = 6)] and healthy subjects (n = 20). The data demonstrated that FRalpha(+) CTCs were detected in blood from NSCLC adenocarcinoma, breast, and ovarian cancer patients, whereas squamous cell lung cancer patients and normal healthy controls lacked FRalpha(+) CTCs as previously known. We demonstrate that CTCs captured using ApoStream((r)) can be used to detect FRalpha(+) CTCs and may have clinical utility as a real-time liquid biopsy for assessing FRalpha levels in cancer patients. PMID- 26848257 TI - Clinical factors affecting intraocular pressure change after orbital decompression surgery in thyroid-associated ophthalmopathy. AB - OBJECTIVE: To report the physiological monitoring of intraocular pressure (IOP) during the postoperative periods after orbital decompression surgery and ascertain the correlation between the clinical factors and IOP changes. METHODS: The medical records of 113 orbits from 60 patients who underwent orbital decompression surgery were reviewed retrospectively. IOP measurement during the postoperative periods was classified based on the postoperative day: week 1 (1-7 days), month 1 (8-41 days), month 2 (42-70 days), month 3 (71-97 days), month 4 (98-126 days), and final (after 127 days). The mean postoperative follow-up was 286.5 days for orbits with at least 6 months of follow-up. Univariate and multivariate linear regression analyses were performed to assess the correlation between the IOP reduction percentage and clinical factors. RESULTS: The mean IOP increased from 16.9 to 18.6 mmHg (10.1%) at postoperative week 1 and decreased to 14.4 mmHg (14.5%) after 2 months. Minimal little changes were observed postoperatively in the IOP after 2 months. Preoperative IOP had a significant positive effect on the reduction percentage both at postoperative week 1 (beta=2.51, P=0.001) and after 2 months (beta=1.07, P=0.029), and the spherical equivalent showed a positive correlation with the reduction level at postoperative week 1 (beta=1.71, P=0.021). CONCLUSION: Surgical decompression caused a significant reduction in the IOP in thyroid-associated orbitopathy, and the amount of reduction was closely related to preoperative IOP; however, it may also cause a transient elevation in the IOP during the early postoperative phase in highly myopic eyes. PMID- 26848258 TI - Dose comparison of conivaptan (Vaprisol(r)) in patients with euvolemic or hypervolemic hyponatremia--efficacy, safety, and pharmacokinetics. AB - PURPOSE: This study aimed to evaluate the efficacy, safety, and pharmacokinetics of 20 and 40 mg/day conivaptan (Vaprisol(r)) in patients with hypervolemic or euvolemic hyponatremia. METHODS: Hyponatremic patients - serum sodium (sNa) <=130 mEq/L - received either 20 or 40 mg/day of conivaptan for 4 days, following an initial 20 mg loading dose. Efficacy was evaluated by the magnitude and extent of change in sNa. Safety was evaluated by the incidence of adverse events, changes in vital signs and laboratory parameters, rate of sNa correction, and frequency of infusion-site reactions. Pharmacokinetic parameters were also measured. RESULTS: A total of 37 patients received 20 mg/day and 214 patients received 40 mg/day conivaptan. Baseline-adjusted sNa-area under the concentration-time curve increased by an average of 753.8+/-499.9 mEq.hr/L (20 mg/day) and 689.2+/-417.3 mEq.hr/L (40 mg/day) over the course of the 4-day treatment period. The majority of patients in both treatment groups achieved a 4 mEq/L increase in sNa over baseline in ~24 hours (82.5%). Average increase in sNa after 4 days was ~10 mEq/L, varying with dosage level and baseline volume status. Treatment success (normal sNa or increase of >=6 mEq/L) was attained by 70.3% of patients in the 20 mg/day group and 72.0% in the 40 mg/day group. CONCLUSION: Both 20 and 40 mg/day doses of conivaptan are efficacious in increasing sNa over 4 days of treatment with no observed increase in the frequency of adverse events or specific infusion site reactions using the higher dose. The pharmacokinetic parameters of both doses were similar to what has been reported previously, exhibiting greater-than dose-proportional plasma concentrations. PMID- 26848259 TI - Short-term maraviroc exposure, a clinical approach to decide on maraviroc prescription in HIV-1-infected treatment-naive patients. PMID- 26848260 TI - Nematode Sodium Calcium Exchangers: A Surprising Lack of Transport. AB - Na(+)/Ca(2+) exchangers are low-affinity, high-capacity transporters that rapidly transport calcium against a gradient of Na(+) ions. Na(+)/Ca(2+) exchangers are divided into three groups based upon substrate specificity: Na(+)/Ca(2+) exchangers (NCX), Na(+)/Ca(2+)/K(+) exchangers (NCKX), and Ca(2+)/cation exchangers (NCLX). In mammals, there are three NCX genes, five NCKX genes, and a single NCLX gene. The genome of the nematode Caenorhabditis elegans contains 10 Na(+)/Ca(2+) exchanger genes: three NCX, five NCLX, and two NCKX genes. In a previous study, we characterized the structural and taxonomic specializations within the family of Na(+)/Ca(2+) exchangers across the phylum Nematoda and observed a complex picture of Na(+)/Ca(2+) exchanger evolution across diverse nematode species. We noted multiple cases of putative gene gain and loss and, most surprisingly, did not detect members of the NCLX type of exchangers within subsets of nematode species. In this commentary, we discuss these findings and speculate on the functional outcomes and physiology of these observations. Our data highlight the importance of studying diverse systems in order to get a deeper understanding of the evolution and regulation of Ca(2+) signaling critical for animal function. PMID- 26848261 TI - Association between frailty and delirium in older adult patients discharged from hospital. AB - BACKGROUND: Delirium and frailty - both potentially reversible geriatric syndromes - are seldom studied together, although they often occur jointly in older patients discharged from hospitals. This study aimed to explore the relationship between delirium and frailty in older adults discharged from hospitals. METHODS: Of the 221 patients aged >65 years, who were invited to participate, only 114 gave their consent to participate in this study. Delirium was assessed using the confusion assessment method, in which patients were classified dichotomously as delirious or nondelirious according to its algorithm. Frailty was assessed using the Edmonton Frailty Scale, which classifies patients dichotomously as frail or nonfrail. In addition to the sociodemographic characteristics, covariates such as scores from the Mini-Mental State Examination, Instrumental Activities of Daily Living scale, and Cumulative Illness Rating Scale for Geriatrics and details regarding polymedication were collected. A multidimensional linear regression model was used for analysis. RESULTS: Almost 20% of participants had delirium (n=22), and 76.3% were classified as frail (n=87); 31.5% of the variance in the delirium score was explained by frailty (R (2)=0.315). Age; polymedication; scores of the Confusion Assessment Method (CAM), instrumental activities of daily living, and Cumulative Illness Rating Scale for Geriatrics; and frailty increased the predictability of the variance of delirium by 32% to 64% (R (2)=0.64). CONCLUSION: Frailty is strongly related to delirium in older patients after discharge from the hospital. PMID- 26848262 TI - Cost-effectiveness of combination therapy umeclidinium/vilanterol versus tiotropium in symptomatic COPD Spanish patients. AB - PURPOSE: Umeclidinium/vilanterol (UMEC/VI) is a novel fixed dose combination of a long-acting muscarinic receptor antagonist (LAMA) and a long-acting beta 2 receptor antagonist (LABA) agent. This analysis evaluated the incremental cost effectiveness ratio (ICER) of UMEC/VI compared with tiotropium (TIO), from the Spanish National Health System (NHS) perspective. METHODS: A previously published linked equations cohort model based on the epidemiological longitudinal study ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End points) was used. Patients included were COPD patients with a post-bronchodilator forced expiratory volume in 1 second (FEV1) <=70% and the presence of respiratory symptoms measured with the modified Medical Research Council dyspnea scale (modified Medical Research Council >=2). Treatment effect, expressed as change in FEV1 from baseline, was estimated from a 24-week head-to-head phase III clinical trial comparing once-daily UMEC/VI with once-daily TIO and was assumed to last 52 weeks following treatment initiation (maximum duration of UMEC/VI clinical trials). Spanish utility values were derived from a published local observational study. Unitary health care costs (?2015) were obtained from local sources. A 3 year time horizon was selected, and 3% discount was applied to effects and costs. Results were expressed as cost/quality-adjusted life years (QALYs). Univariate and probabilistic sensitivity analysis (PSA) was performed. RESULTS: UMEC/VI produced additional 0.03 QALY and ?590 vs TIO, leading to an ICER of ?21,475/QALY. According to PSA, the probability of UMEC/VI being cost-effective was 80.3% at a willingness-to-pay of ?30,000/QALY. CONCLUSION: UMEC/VI could be considered as a cost-effective treatment alternative compared with TIO in symptomatic COPD patients from the Spanish NHS perspective. PMID- 26848263 TI - Fullerene mediates proliferation and cardiomyogenic differentiation of adipose derived stem cells via modulation of MAPK pathway and cardiac protein expression. AB - Zero-dimensional fullerenes can modulate the biological behavior of a variety of cell lines. However, the effects and molecular mechanisms of proliferation and cardiomyogenic differentiation in brown adipose-derived stem cells (BADSCs) are still unclear. In this study, we report the initial biological effects of fullerene-C60 on BADSCs at different concentrations. Results suggest that fullerene-C60 has no cytotoxic effects on BADSCs even at a concentration of 100 MUg/mL. Fullerene-C60 improves the MAPK expression level and stem cell survival, proliferation, and cardiomyogenesis. Further, we found that the fullerene-C60 modulates cardiomyogenic differentiation. Fullerene-C60 improves the expression of cardiomyocyte-specific proteins (cTnT and alpha-sarcomeric actinin). At elevated concentration, fullerene-C60 reduces the incidence of diminished spontaneous cardiac differentiation of BADSCs with time. At the genetic level, fullerene-C60 (5 MUg/mL) also improves the expression of cTnT. In addition, fullerene-C60 promotes the formation of gap junction among cells. These findings have important implications for clinical application of fullerenes in the treatment of myocardial infarction. PMID- 26848264 TI - Controlled-release of tetracycline and lovastatin by poly(D,L-lactide-co glycolide acid)-chitosan nanoparticles enhances periodontal regeneration in dogs. AB - Chronic periodontitis is characterized by inflammation of periodontal tissues, leading to bone resorption and tooth loss. The goal of treatment is to regenerate periodontal tissues including bone and cementum lost as a consequence of disease. The local delivery of tetracycline was proven to be effective in controlling localized periodontal infection without apparent side effects. Previous studies suggested that lovastatin has a significant role in new bone formation; however, the local delivery of lovastatin might enhance its therapeutic effects. A number of local delivery devices have been developed recently, including poly(D,L lactide-co-glycolide acid) (PLGA) nanoparticles. The aim of this study was to develop a local delivery device, PLGA-lovastatin-chitosan-tetracycline nanoparticles, which allows the sequential release of tetracycline and lovastatin to effectively control local infection and promote bone regeneration in periodontitis. The size and microstructure of nanoparticles were examined by transmission electron microscopy, Nanoparticle Size Analyzer, and Fourier transform infrared spectroscopy. The release of tetracycline and lovastatin was quantified using a UV-Vis spectrophotometer. Furthermore, the cytotoxic effect and alkaline phosphatase activity of the nanoparticles in osteoblast cell cultures as well as antibacterial activity against periodontal pathogens were investigated. Finally, the bone regeneration potential of PLGA nanoparticles in three-walled defects in beagle dogs was investigated. The results indicated that PLGA-lovastatin-chitosan-tetracycline nanoparticles showed good biocompatibility, antibacterial activity, and increased alkaline phosphatase activity. The volumetric analysis from micro-CT revealed significantly increased new bone formation in defects filled with nanoparticles in dogs. This novel local delivery device might be useful as an adjunctive treatment in periodontal regenerative therapy. PMID- 26848266 TI - The differences in temperament-character traits, suicide attempts, impulsivity, and functionality levels of patients with bipolar disorder I and II. AB - BACKGROUND: The primary aim of this study was to compare the differences in temperament-character traits, suicide attempts, impulsivity, and functionality levels of patients with bipolar disorder I (BD-I) and bipolar disorder II (BD II). METHODS: Fifty-two BD-I patients and 49 BD-II patients admitted to Erenkoy Mental and Neurological Disease Training and Research Hospital psychiatry clinic and fifty age- and sex-matched healthy control subjects were enrolled in this study. A structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis I Disorders, Temperament and Character Inventory, Barrett Impulsiveness Scale-11 (BIS-11), Hamilton Depression Inventory Scale, Young Mania Rating Scale, and Bipolar Disorder Functioning Questionnaire (BDFQ) were administered to patients and to control group. RESULTS: No statistically significant difference in sociodemographic features existed between the patient and control groups (P>0.05). Thirty-eight subjects (37.62%) in the patient group had a suicide attempt. Twenty-three of these subjects (60.52%) had BD-I, and 15 of these subjects (39.47%) had BD-II. Suicide attempt rates in BD-I and II patients were 60.52% and 39.47%, respectively (P<0.05). Comparison of BD-I and II patients with healthy control subjects revealed that cooperativeness (C), self-directedness (Sdi), and self-transcendence (ST) scores were lower and novelty seeking (NS1 and NS2), harm avoidance (HA4), and reward dependence (RD2) subscale scores were higher in patients with BD-I. When BD-I patients were compared with BD-II patients, BIS-11 (attention) scores were higher in patients with BD-II and BIS-11 (motor and nonplanning impulsivity) scores were higher in patients with BD-I. According to BDFQ, relations with friends, participation in social activities, daily activities and hobbies, and occupation subscale scores were lower and taking initiative subscale scores were higher in patients with BD I. Social withdrawal subscale scores were higher in patients with BD-II. CONCLUSION: In our study, NS, HA, and RD scores that may be found high in suicide attempters and Sdi scores that may be found low in suicide attempters were as follows: NS1, NS2, HA4, and RD2 subscale scores were high and Sdi scores were low in patients with BD-I, suggesting a higher rate of suicide attempts in this group of patients. In addition, C and Sdi scores that indicate a predisposition to personality disorder were significantly lower in patients with BD-I than patients with BD-II and healthy controls, suggesting a higher rate of personality disorder comorbidity in patients with BD-I. Higher impulsivity and suicidality rates and poorer functionality in patients with BD-I also suggest that patients with BD-I may be more impulsive and more prone to suicide and have poorer functionality in some areas. PMID- 26848265 TI - The crossroads of anxiety: distinct neurophysiological maps for different symptomatic groups. AB - BACKGROUND: Despite the devastating impact of anxiety disorders (ADs) worldwide, long-lasting debates on causes and remedies have not solved the clinician's puzzle: who should be treated and how? Psychiatric classifications conceptualize ADs as distinct entities, with strong support from neuroscience fields. Yet, comorbidity and pharmacological response suggest a single "serotonin dysfunction" dimension. Whether AD is one or several disorders goes beyond academic quarrels, and the distinction has therapeutic relevance. Addressing the underlying dysfunctions should improve treatment response. By its own nature, neurophysiology can be the best tool to address dysfunctional processes. PURPOSE: To search for neurophysiological dysfunctions and differences among panic disorder (PD), agoraphobia-social-specific phobia, obsessive-compulsive disorder (OCD) and generalized anxiety disorder. METHODS: A sample population of 192 unmedicated patients and 30 aged-matched controls partook in this study. Hypothesis-related neurophysiological variables were combined into ten independent factors: 1) dysrhythmic patterns, 2) delta, 3) theta, 4) alpha, 5) beta (whole-head absolute power z-scores), 6) event-related potential (ERP) combined latency, 7) ERP combined amplitude (z-scores), 8) magnitude, 9) site, and 10) site of hyperactive networks. Combining single variables into representative factors was necessary because, as in all real-life phenomena, the complexity of interactive processes cannot be addressed through single variables and the multiplicity of potentially implicated variables would demand an extremely large sample size for statistical analysis. RESULTS: The nonparametric analysis correctly classified 81% of the sample. Dysrhythmic patterns, decreased delta, and increased beta differentiated AD from controls. Shorter ERP latencies were found in several individual patients, mostly from the OCD group. Hyperactivities were found at the right frontorbital-striatal network in OCD and at the panic circuit in PD. CONCLUSIONS: Our findings support diffuse cortical instability in AD in general, with individual differences in information processing deficits and regional hyperactivities in OCD and PD. Study limitations and the rationale behind the variable selection and combination strategy will be discussed before addressing the therapeutic implications of our findings. PMID- 26848267 TI - Psychogenic nonepileptic seizures as a manifestation of psychological distress associated with undiagnosed autism spectrum disorder. AB - Psychogenic nonepileptic seizures (PNES) are observable changes in behavior or consciousness that are similar to epileptic seizures but are not associated with electrophysiologic changes. PNES occur in children with underlying psychological distress and are especially frequent in those with epilepsy. Because PNES are heterogeneous, comprehensive treatment tailored to each patient is required to reduce psychosocial stress. Currently, reports regarding children with PNES concomitant with autism spectrum disorder (ASD) do not exist, and effective treatment strategies for these children are lacking. In this case report, we describe a 10-year-old Japanese girl with undiagnosed ASD who developed PNES while undergoing treatment for benign childhood epilepsy with centrotemporal spikes. She exhibited hypersensitivity to sound and interpersonal conflicts caused by social communication deficits. The PNES symptoms improved shortly after our intervention, which was designed to reduce her distress caused by auditory hypersensitivity and impaired social communication, both characteristics of ASD. To the best of our knowledge, this is the first report describing PNES in a child with ASD. Our findings suggest that PNES can result from psychological distress in children with undiagnosed ASD and highlight the importance of examining ASD traits in patients with PNES. PMID- 26848269 TI - Effects of propofol versus sevoflurane on cerebral oxygenation and cognitive outcome in patients with impaired cerebral oxygenation. AB - BACKGROUND: Postoperative neurocognitive dysfunction induced by anesthetics, particularly in elderly patients with impaired oxygenation, is a common complication of surgery and is eliciting increased interest in clinical practice. To investigate the effects of anesthetics on neurocognition, we compared the effects of propofol versus sevoflurane on cerebral oxygenation and cognitive outcome in patients with impaired cerebral oxygenation undergoing general anesthesia. METHODS: Sixty-three patients with impaired cerebral oxygenation (jugular venous bulb oxygen saturation [SjvO2] <50%) or cerebral blood flow/cerebral metabolic rate of oxygen ([CBF/CMRO2] <=15%) undergoing elective abdominal surgery were randomly allocated into propofol group (group P) or sevoflurane group (group S). The clinical parameters and jugular venous bulb blood gas analysis were monitored throughout the surgical procedure. Cognitive function was assessed with the mini-mental state examination and Montreal Cognitive Assessment at day 1 and day 7 following surgery. S100beta protein in plasma was measured using enzyme-linked immunosorbent assay. RESULTS: The SjvO2 increased during anesthesia induction and surgery when compared to baseline but had no significant difference between group P and group S. When compared to baseline, the CBF/CMRO2 was increased only at the end of surgery and extubation in group P; however, the CBF/CMRO2 in group S was increased during anesthesia induction at 1 hour, 2 hours, end of surgery, and extubation. Furthermore, the CBF/CMRO2 in group S was significantly higher than that in group P during anesthesia induction at 1 hour, 2 hours, and end of surgery. S100beta protein did not significantly change at extubation and 1 day after surgery in both groups when compared to baseline. There was no significant difference in mini-mental state examination and Montreal Cognitive Assessment scores between group P and group S at all time points. CONCLUSION: Sevoflurane showed similar effects in postoperative neurocognitive function as propofol but could improve cerebral oxygenation in patients with impaired cerebral oxygenation. PMID- 26848268 TI - A 5-year retrospective study of demographic, anamnestic, and clinical factors related to psychiatric hospitalizations of adolescent patients. AB - BACKGROUND: Psychiatric emergencies of children and adolescents have greatly increased during the last years, but this phenomenon has not been studied in detail. The aim of this study was to analyze the correlation between acute psychiatric hospitalizations of adolescents and selected variables to highlight risk factors for psychiatric emergencies. METHODS: This retrospective research was conducted in the acute psychiatric public ward, Service of Psychiatric Diagnosis and Treatment (SPDT), and in the residential facility for adolescents, "The Medlar", located in Modena. The sample was constituted by all adolescent patients (n=101, age range 14-18) who had acute hospitalizations (n=140) in SPDT and had been successively transferred to "The Medlar" (n=83), from February 2, 2010 to January 31, 2015. From clinical charts, we extracted demographic and anamnestic characteristics of patients and clinical variables related to hospitalizations. Data were statistically analyzed. RESULTS: Sixty-one percent of our patients lived with one divorced parent, with adoptive or immigrant family, or in institutions; 51% had experienced stressful events during childhood; 81% had a normal intellective level, but only 6% presented regular school performance. Parental psychiatric illness was negatively related, in a statistically significantly way, with onset age of adolescent mental disorders (coefficient -2.28, 95% confidence interval [CI]: -3.53 to 1.01, P<0.001, single linear regression; odds ratio: 4.39, 95% CI: 1.43-13.47, P<0.010, single logistic regression). The most frequent reasons for admission were aggressive behavior in males and suicide risk in females (P=0.002). The most frequent psychiatric diagnosis at SPDT discharge was "conduct disorder", more frequent in males, followed by "adjustment disorder", more frequent in females (P=0.001). In SPDT, the adolescent hospitalizations progressively increased fivefold at the end of the observation period. CONCLUSION: Our results overlap the worldwide trend of increasing adolescent psychiatric hospitalizations, suggest risk factors like parental psychiatric illness and early life stressful events, and highlight the different prevalence of aggressiveness and suicide in males and females. PMID- 26848270 TI - Single sternal metastasis due to malignant melanoma with unexpected long-term survival: a case report. AB - Metastases from melanoma have a very poor prognosis for the patient. Single metastatic lesions in the sternum due to melanoma are extremely rare. A rare case of a presternal mass in a 56-year-old patient who had undergone excision for malignant melanoma is presented. Review of the patient's history and surgical resection of a single metastatic soft tissue lesion offer the best chance of long term survival. PMID- 26848271 TI - Prognostic implications of immunohistochemistry markers for EGFR-TKI therapy in Chinese patients with advanced lung adenocarcinoma harboring EGFR mutations. AB - BACKGROUND: Epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer predict dramatic clinical responses to tyrosine kinase inhibitor (TKI) treatment. The conclusion on EGFR mutation-specific antibodies by immunohistochemistry (IHC) is not consistent. We evaluated the clinical availability of EGFR mutation-specific antibodies, investigating the prediction role of mutant EGFRs and other IHC markers in TKI therapy in patients with advanced lung adenocarcinoma. MATERIALS AND METHODS: We analyzed 637 primary lung adenocarcinomas from an unselected Chinese population. For IHC, antibodies against EGFR exon 19 E746_A750 deletions, exon 21 L858R mutations, thyroid transcription factor-1 (TTF-1), and Napsin-A were applied. Positivity was defined as staining score >0. RESULTS: Specificities of E746_A750 and L858R antibodies were 99.6% and 99.3%, while sensitivities were 86.0% and 82.7%, respectively. Tumors with Napsin-A positivity, TTF-1 positivity, EGFR mutations, and lepidic pattern showed a lower marker of proliferation index (Ki67). Higher expression scores of mutant EGFR protein, TTF-1 positivity, lower Ki67 proliferation index, and lepidic pattern were associated with longer progression-free survival. CONCLUSION: High scores of mutant EGFR, Napsin-A positivity, TTF-1 positivity, lower Ki67 index, and lepidic pattern were favorable predictors for TKI therapy in patients with advanced lung adenocarcinoma. PMID- 26848272 TI - A critical appraisal of once-daily topical luliconazole for the treatment of superficial fungal infections. AB - Luliconazole is a novel imidazole derivative, which has demonstrated in vitro efficacy against dermatophytes and Candida. The results from Phase III trials show that luliconazole 1% cream applied once daily for 2 weeks successfully resolved the clinical signs and symptoms as well as eradicated the pathologic fungi, which cause tinea pedis. A 1-week treatment with luliconazole 1% cream also produced favorable clinical and mycological results in clinical trials for tinea corporis and tinea cruris. Across trials, adverse events consisted mainly of localized reactions following application. The development of a new antifungal agent is timely due to mounting resistance among existing treatments. Because luliconazole requires a short duration of treatment, it may assist in reducing disease recurrence as a result of patient nonadherence. PMID- 26848273 TI - A local renal renin-angiotensin system activation via renal uptake of prorenin and angiotensinogen in diabetic rats. AB - The mechanism of activation of local renal renin-angiotensin system (RAS) has not been clarified in diabetes mellitus (DM). We hypothesized that the local renal RAS will be activated via increased glomerular filtration and tubular uptake of prorenin and angiotensinogen in diabetic kidney with microalbuminuria. Streptozotocin (STZ)-induced DM and control rats were injected with human prorenin and subsequently with human angiotensinogen. Human prorenin uptake was increased in podocytes, proximal tubules, macula densa, and cortical collecting ducts of DM rats where prorenin receptor (PRR) was expressed. Co immunoprecipitation of kidney homogenates in DM rats revealed binding of human prorenin to the PRR and to megalin. The renal uptake of human angiotensinogen was increased in DM rats at the same nephron sites as prorenin. Angiotensin converting enzyme was increased in podocytes, but decreased in the proximal tubules in DM rats, which may have contributed to unchanged renal levels of angiotensin despite increased angiotensinogen. The systolic blood pressure increased more after the injection of 20 MUg of angiotensinogen in DM rats than in controls, accompanied by an increased uptake of human angiotensinogen in the vascular endothelium. In conclusion, endocytic uptake of prorenin and angiotensinogen in the kidney and vasculature in DM rats was contributed to increased tissue RAS and their pressor response to angiotensinogen. PMID- 26848274 TI - Efficacy of ultrasound-guided transversus abdominis plane block for postoperative analgesia in patients undergoing inguinal hernia repair. AB - BACKGROUND AND AIM: Transversus abdominis plane block (TAP block) is a novel procedure to provide postoperative analgesia following inguinal hernia surgery. The utilization of ultrasound has greatly augmented the success rate of this block and additionally avoiding complications. The aim of our study was to gauge the analgesic efficacy of ultrasound-guided TAP block in patients undergoing unilateral inguinal hernia repair. MATERIALS AND METHODS: Sixty patients scheduled for elective inguinal hernia repair were selected for the study. At the end of the surgical procedure, they were randomly divided into two groups. Ultrasound-guided TAP block was performed with 20 mL of ropivacaine 0.2% (group A) or normal saline (group B). Visual analog scale (VAS) scores were used to assess pain. Paracetamol was given if VAS > 3 and tramadol was used when VAS > 6. Patients were monitored for VAS scores and total analgesic consumption for the 24 hour period. RESULTS: The TAP block with ropivacaine (group A) reduced VAS scores at 4, 6, and 12 hours. There was no distinction in VAS scores at 0, 2, and 24 hours between the two groups. The duration of analgesia for TAP block with ropivacaine lasted for 390 minutes. Total analgesics consumption was also significantly reduced in group A than group B. No complication was reported to TAP block in both the groups. CONCLUSION: The ultrasound-guided TAP block provides good postoperative analgesia, reduces analgesic requirements, and provides good VAS scores with fewer complications following inguinal hernia surgery. PMID- 26848275 TI - Basilic Vein Transposition Used as a Tertiary Vascular Access for Hemodialysis: 15 Years of Experience. AB - INTRODUCTION: The quality of the life in patients requiring long term hemodialysis is directly proportional to the long-term patency of their vascular access. Basilic vein transposition for vascular access (BAVA) represents a suitable option for creating a tertiary native vascular access for hemodialysis on the upper extremities for patients requiring long term hemodialysis. The purpose of the study is to compare BAVAs with arteriovenous grafts (AVG). METHOD: Data collection was based on selecting all of the patients with BAVA created in the time period in between January 1996 and August 2011. A questionnaire was created and sent to the selected hemodialysis centers. The resulting set of data was statistically analyzed and evaluated. RESULTS: In the time period between 1 January 1996 and August 2011, arteriovenous access for hemodialysis was created in 6754 patients (7203 procedures in total). Out of these patients, 175 BAVAs were created. Our patient database of those undergoing the BAVA procedure consisted of 98 females (56%) and 77 males (44%) with an average age of 64.5 years. The prevalence of diabetes mellitus was 60% (105 patients). Primary patency after 12 months was 68.8%, 24 months 59.7%, 36 months 53.8, 48 months 53.8%, and 60 months 50%. Primary assisted patency after 12 months was 89.9%, 24 months 84.6%, 36 months 77.8%, 48 months 77.9%, 60 months 70.8%. Secondary patency after 12 months was 89.4%, 24 months 86.9%, 36 months 81%, 48 months 78.9%, 60 months 75.7%. Twenty-nine BAVAs (16.5%) were obliterated. CONCLUSION: Patients benefit from this type of procedure due to the longer patency of a native arteriovenous access, as well as a lower incidence of infectious complications. PMID- 26848277 TI - Economic and clinical benefits of endometrial radiofrequency ablation compared with other ablation techniques in women with menorrhagia: a retrospective analysis with German health claims data. AB - OBJECTIVE: To evaluate the economic and clinical benefits of endometrial radiofrequency ablation (RFA) compared with other ablation techniques for the treatment of menorrhagia. METHODS: Using German health claims data, women meeting defined inclusion criteria for the intervention group (RFA) were selected. A comparable control group (other endometrial ablations) was established using propensity score matching. These two groups were compared during the quarter of treatment (QoT) and a follow-up of 2 years for the following outcomes: costs during QoT and during follow-up, repeated menorrhagia diagnoses during follow-up and necessary retreatments during follow-up. RESULTS: After performing propensity score matching, 50 cases could be allocated to the intervention group, while 38 were identified as control cases. Patients in the RFA group had 5% fewer repeat menorrhagia diagnoses (40% vs 45%; not significant) and 5% fewer treatments associated with recurrent menorrhagia (6% vs 11%; not significant) than cases in the control group. During the QoT, the RFA group incurred ?578 additional costs (?2,068 vs ?1,490; ns). However, during follow-up, the control group incurred ?1,254 additional costs (?4,561 vs ?5,815; ns), with medication, outpatient physician consultations, and hospitals costs being the main cost drivers. However, none of the results were statistically significant. CONCLUSION: Although RFA was more cost-intensive in the QoT compared with other endometrial ablation techniques, an average total savings of ?676 was generated during the follow-up period. While having evidence that RFA is clinically equivalent to other endometrial ablation procedures, we generated indications that RFA is non inferior and favorable with regard to economic outcomes. PMID- 26848278 TI - Cardiac resynchronization therapy pacemaker: critical appraisal of the adaptive CRT-P device. AB - Cardiac resynchronization therapy (CRT) is an effective and well-established therapy for patients suffering with heart failure, left ventricular (LV) systolic dysfunction (ejection fraction <=35%), and electrical dyssynchrony, demonstrated by a surface QRS duration of >=120 ms. Patients undergoing treatment with CRT have shown significant improvement in functional class, quality of life, LV ejection fraction, exercise capacity, hemodynamics, and reverse remodeling of LV, and ultimately, morbidity and mortality. However, 30%-40% of patients who receive a CRT device may not show improvement, and they are termed as non responders. The nonresponders have a poor prognosis; several methods have been developed to try to enhance response to CRT. Echocardiography-guided optimization of CRT has not resulted in significant clinical benefit, since it is done at rest with the patient in supine position. An ideal optimization strategy would provide continuous monitoring and adjustment of device pacing to provide maximal cardiac resynchronization, under a multitude of physiologic states. Intrinsic activation of the right ventricle (RV) with paced activation of the RV, even in the setting of biventricular (BiV) pacing, may result in an adverse effect on cardiac performance. With this physiology, the use of LV-only pacing may be preferred and may enhance CRT. Adaptive CRT is a novel device-based algorithm that was designed to achieve patient-specific adjustment in CRT so as to provide appropriate BiV pacing or LV-only pacing. This article will review the goals of CRT optimization, and implementation and outcomes associated with adaptive CRT. PMID- 26848279 TI - Experimental measurement on movement of spiral-type capsule endoscope. AB - Wireless capsule endoscope achieved great success, however, the maneuvering of wireless capsule endoscope is challenging at present. A magnetic driving instrument, including two bar magnets, a stepper motor, a motor driver, a motor controller, and a power supplier, was developed to generate rotational magnetic fields. Permanent magnet ring, magnetized as S and N poles radially and mounted spiral structure on the surface, acted as a capsule. The maximum torque passing to the capsule, rotational synchronization of capsule and motor, and the translational speed of capsule, were measured in ex vivo porcine large intestine. The experimental results illustrate that the rotational movement of the spiral type capsule in the intestine is feasible and the cost of the magnetic driving equipment is low. As a result, the solution is promising in the future controllability. PMID- 26848280 TI - Sleep, eating disorder symptoms, and daytime functioning. AB - OBJECTIVE: To investigate the relationship between eating disorders, body mass index (BMI), sleep disorders, and daytime functioning. DESIGN: Survey. SETTING: The Netherlands. PARTICIPANTS: N=574 Dutch young adults (18-35 years old). MEASUREMENTS: Participants completed a survey on eating and sleep habits including the Eating Disorder Screen for Primary care (ESP) and SLEEP-50 questionnaire subscales for sleep apnea, insomnia, circadian rhythm disorder (CRD), and daytime functioning. SLEEP-50 outcomes of participants who screened negative (<=2) and positive (>2) on the ESP were compared. In addition, SLEEP-50 scores of groups of participants with different ESP scores (0-4) and different BMI groups (ie, underweight, healthy weight, overweight, and obese) were compared using nonparametric statistics. RESULTS: Almost 12% (n=67) of participants screened positive for having an eating disorder. Relative to participants without eating disorders, participants who screened positive for eating disorders reported significantly higher scores on sleep apnea (3.7 versus 2.9, P=0.012), insomnia (7.7 versus 5.5, P<0.0001), CRD (2.9 versus 2.3, P=0.011), and impairment of daytime functioning (8.8 versus 5.8, P=0.0001). ESP scores were associated with insomnia (r=0.117, P=0.005), sleep apnea (r=0.118, P=0.004), sleep quality (r=-0.104, P=0.012), and daytime functioning (r=0.225, P<0.0001), but not with CRD (r=0.066, P=0.112). BMI correlated significantly with ESP scores (r=0.172, P<0.0001) and scores on sleep apnea (r=0.171, P<0.0001). When controlling for BMI, the partial correlation between ESP and sleep apnea remained significant (r=0.10, P=0.015). CONCLUSION: Participants who score positive for eating disorders scored significantly higher on sleep disorder scales, and reported significantly more impairment of daytime functioning. PMID- 26848281 TI - Relationship between HMGB1 and PAI-1 after allogeneic hematopoietic stem cell transplantation. AB - BACKGROUND: Conditioning regimens including total body irradiation (TBI) or cyclophosphamide can mobilize high-mobility group box 1 (HMGB1) to peripheral blood. Additionally, increased plasminogen activator inhibitor (PAI)-1 levels are associated with post-allogeneic hematopoietic stem cell transplantation (aHSCT). However, changes to circulating levels of HMGB1 after aHSCT are poorly understood. MATERIALS AND METHODS: The study cohort included 289 patients who underwent aHSCT at one of 25 institutions in Japan. We have investigated the relationship between HMGB1 and PAI-1 following aHSCT. A significant increase in HMGB1 levels occurred after conditioning treatment. Additionally, levels of HMGB1 at day 0 were significantly increased in TBI+ patients and cyclophosphamide/TBI patients. CONCLUSION: Our data revealed that an increased level of HMGB1 at day 0 following aHSCT correlates with increased PAI-1 after aHSCT, which is consistent with previous reports. Increased HMGB1 at day 0 after a conditioning regimen may play a role in transplantation-associated coagulopathy following aHSCT, because PAI-1 can accelerate procoagulant activity. PMID- 26848282 TI - Peer-assisted learning in medical school: tutees' perspective. AB - PURPOSE: Peer tutoring offers a valuable method of enhancing students' learning experience in medical school. Junior students learn from senior peers to reinforce curriculum content in an engaging community environment. The aim of our study was to assess tutees' perceptions of a formal peer tutoring program at the Central Clinical School of Sydney Medical School. We used the learning theory of the community of practice in order to understand tutees' perspectives. PATIENTS AND METHODS: All Year 1 and Year 2 students within the Central Clinical School were invited to be tutored by Year 3 and Year 4 students, respectively. Tutor pairs taught a group of three to four tutees fortnightly, and the tutorials were largely clinically based. A questionnaire containing 13 closed items and four open-ended questions regarding their experiences in the program was distributed to the tutees. Descriptive statistics were used to analyze the data. RESULTS: A total of 66 of 101 (65%) Year 1 and Year 2 students took part as tutees and 42 of 106 (40%) students as tutors. The tutees' response rate was 53% (35/66). Results were largely positive, with 97% of the tutees enjoying the program, 90% showing interest in tutorial topics, 91% feeling a sense of community, 100% wanting to take part next year, 97% finding small groups effective, and 97% and 91% feeling an improved understanding of medical concepts and clinical skills, respectively. Tutees perceived the most useful aspects to be learning and revision and advice from experienced peers. The most frequent suggestion for improvement was to resolve scheduling conflicts. CONCLUSION: Tutees found the peer tutoring program to be valuable in learning and revision, establishing a community, and gaining practical skills and advice through a small-group format. The community of practice framework was useful in identifying these areas of benefit, demonstrating that a peer tutoring program such as this can provide an enhanced learning environment for tutees. PMID- 26848276 TI - Neuroprotective Effects Against POCD by Photobiomodulation: Evidence from Assembly/Disassembly of the Cytoskeleton. AB - Postoperative cognitive dysfunction (POCD) is a decline in memory following anaesthesia and surgery in elderly patients. While often reversible, it consumes medical resources, compromises patient well-being, and possibly accelerates progression into Alzheimer's disease. Anesthetics have been implicated in POCD, as has neuroinflammation, as indicated by cytokine inflammatory markers. Photobiomodulation (PBM) is an effective treatment for a number of conditions, including inflammation. PBM also has a direct effect on microtubule disassembly in neurons with the formation of small, reversible varicosities, which cause neural blockade and alleviation of pain symptoms. This mimics endogenously formed varicosities that are neuroprotective against damage, toxins, and the formation of larger, destructive varicosities and focal swellings. It is proposed that PBM may be effective as a preconditioning treatment against POCD; similar to the PBM treatment, protective and abscopal effects that have been demonstrated in experimental models of macular degeneration, neurological, and cardiac conditions. PMID- 26848283 TI - Measuring efficiency of governmental hospitals in Palestine using stochastic frontier analysis. AB - BACKGROUND: The Palestinian government has been under increasing pressure to improve provision of health services while seeking to effectively employ its scare resources. Governmental hospitals remain the leading costly units as they consume about 60 % of governmental health budget. A clearer understanding of the technical efficiency of hospitals is crucial to shape future health policy reforms. In this paper, we used stochastic frontier analysis to measure technical efficiency of governmental hospitals, the first of its kind nationally. METHODS: We estimated maximum likelihood random-effects and time-invariant efficiency model developed by Battese and Coelli, 1988. Number of beds, number of doctors, number of nurses, and number of non-medical staff, were used as the input variables, and sum of number of treated inpatients and outpatients was used as output variable. Our dataset includes balanced panel data of 22 governmental hospitals over a period of 6 years. Cobb-Douglas function, translog function, and multi-output distance function were estimated using STATA 12. RESULTS: The average technical efficiency of hospitals was approximately 55 %, and ranged from 28 to 91 %. Doctors and nurses appear to be the most important factors in hospital production, as 1 % increase in number of doctors, results in an increase in the production of the hospital of 0.33 and 0.51 %, respectively. If hospitals increase all inputs by 1 %, their production would increase by 0.74 %. Hospitals production process has a decrease return to scale. CONCLUSION: Despite continued investment in governmental hospitals, they remained relatively inefficient. Using the existing amount of resources, the amount of delivered outputs can be improved 45 % which provides insight into mismanagement of available resources. To address hospital inefficiency, it is important to increase the numbers of doctors and nurses. The number of non-medical staff should be reduced. Offering the option of early retirement, limit hiring, and transfer to primary health care centers are possible options. It is crucial to maintain a rich clinical skill-mix when implementing such measures. Adopting interventions to improve the quality of management in hospitals will improve efficiency. International benchmarking provides more insights on sources of hospital inefficiency. PMID- 26848284 TI - Metrics for Success: Strategies for Enabling Core Facility Performance and Assessing Outcomes. AB - Core Facilities are key elements in the research portfolio of academic and private research institutions. Administrators overseeing core facilities (core administrators) require assessment tools for evaluating the need and effectiveness of these facilities at their institutions. This article discusses ways to promote best practices in core facilities as well as ways to evaluate their performance across 8 of the following categories: general management, research and technical staff, financial management, customer base and satisfaction, resource management, communications, institutional impact, and strategic planning. For each category, we provide lessons learned that we believe contribute to the effective and efficient overall management of core facilities. If done well, we believe that encouraging best practices and evaluating performance in core facilities will demonstrate and reinforce the importance of core facilities in the research and educational mission of institutions. It will also increase job satisfaction of those working in core facilities and improve the likelihood of sustainability of both facilities and personnel. PMID- 26848285 TI - Disaster and Contingency Planning for Scientific Shared Resource Cores. AB - Progress in biomedical research is largely driven by improvements, innovations, and breakthroughs in technology, accelerating the research process, and an increasingly complex collaboration of both clinical and basic science. This increasing sophistication has driven the need for centralized shared resource cores ("cores") to serve the scientific community. From a biomedical research enterprise perspective, centralized resource cores are essential to increased scientific, operational, and cost effectiveness; however, the concentration of instrumentation and resources in the cores may render them highly vulnerable to damage from severe weather and other disasters. As such, protection of these assets and the ability to recover from a disaster is increasingly critical to the mission and success of the institution. Therefore, cores should develop and implement both disaster and business continuity plans and be an integral part of the institution's overall plans. Here we provide an overview of key elements required for core disaster and business continuity plans, guidance, and tools for developing these plans, and real-life lessons learned at a large research institution in the aftermath of Superstorm Sandy. PMID- 26848286 TI - Recognizing Medication related Entities in Hospital Discharge Summaries using Support Vector Machine. AB - Due to the lack of annotated data sets, there are few studies on machine learning based approaches to extract named entities (NEs) in clinical text. The 2009 i2b2 NLP challenge is a task to extract six types of medication related NEs, including medication names, dosage, mode, frequency, duration, and reason from hospital discharge summaries. Several machine learning based systems have been developed and showed good performance in the challenge. Those systems often involve two steps: 1) recognition of medication related entities; and 2) determination of the relation between a medication name and its modifiers (e.g., dosage). A few machine learning algorithms including Conditional Random Field (CRF) and Maximum Entropy have been applied to the Named Entity Recognition (NER) task at the first step. In this study, we developed a Support Vector Machine (SVM) based method to recognize medication related entities. In addition, we systematically investigated various types of features for NER in clinical text. Evaluation on 268 manually annotated discharge summaries from i2b2 challenge showed that the SVM-based NER system achieved the best F-score of 90.05% (93.20% Precision, 87.12% Recall), when semantic features generated from a rule-based system were included. PMID- 26848287 TI - Collaboration: a Simple Recipe for Improving Research Productivity in the Community Teaching Hospital Setting. AB - The Medical Library and the Department of Research of the Staten Island University Hospital developed a collaborative project aimed at improving research and scholarly productivity in the community teaching hospital setting to meet teaching program accreditation requirements. The project opens a new venue for hospital librarians seeking new and innovative roles within their institutions while helping to strengthen the library's position and demonstrate the value of library services to health professionals. PMID- 26848288 TI - Mind the Gap in the Middle: A Call to Study Midlife. AB - Although the study of midlife has increased somewhat over the last decade, middle aged adults are often omitted from research on adult development and aging. Possible reasons for the lack of attention to middle age are considered and recommendations for ways to increase research on midlife are suggested to generate new knowledge and to dispel the myths. Findings related to the happiness curve and the midlife crisis are discussed in the context of addressing misconceptions. A model of midlife as a pivotal period in the life course at the intersection of growth and decline is presented. Closing the research gap in the middle of the life course will help to further our understanding of this understudied age period. The findings can inform interventions to promote well being among the middle-aged with concomitant benefits for the welfare of those younger and older who depend on them. PMID- 26848289 TI - Multi-platform metabolomics analyses of a broad collection of fragrant and non fragrant rice varieties reveals the high complexity of grain quality characteristics. AB - The quality of rice in terms not only of its nutritional value but also in terms of its aroma and flavour is becoming increasingly important in modern rice breeding where global targets are focused on both yield stability and grain quality. In the present paper we have exploited advanced, multi-platform metabolomics approaches to determine the biochemical differences in 31 rice varieties from a diverse range of genetic backgrounds and origin. All were grown under the specific local conditions for which they have been bred and all aspects of varietal identification and sample purity have been guaranteed by local experts from each country. Metabolomics analyses using 6 platforms have revealed the extent of biochemical differences (and similarities) between the chosen rice genotypes. Comparison of fragrant rice varieties showed a difference in the metabolic profiles of jasmine and basmati varieties. However with no consistent separation of the germplasm class. Storage of grains had a significant effect on the metabolome of both basmati and jasmine rice varieties but changes were different for the two rice types. This shows how metabolic changes may help prove a causal relationship with developing good quality in basmati rice or incurring quality loss in jasmine rice in aged grains. Such metabolomics approaches are leading to hypotheses on the potential links between grain quality attributes, biochemical composition and genotype in the context of breeding for improvement. With this knowledge we shall establish a stronger, evidence-based foundation upon which to build targeted strategies to support breeders in their quest for improved rice varieties. PMID- 26848291 TI - Overactive bladder syndrome pharmacotherapy: future treatment options. AB - Overactive bladder syndrome (OAB) is a lifestyle disease and its incidence increases with age. Although it is not a life-threatening disease, it is known to have a significant impact on the quality of life. The first-choice pharmacological treatment of OAB is antimuscarinics. However, their limited clinical effectiveness and unsatisfactory tolerance profile, combined with the advancement of knowledge on the aetiopathogenesis of the disease, have inspired research on new pharmacotherapy options for OAB. Basic research has provided foundations for the development of new OAB treatments, which seem very promising and can be applied in clinical practice. The mechanisms of the studied compounds are based on their effect on certain receptors and neurotransmitters that contribute to regulating the micturition reflex. These compounds are not only more receptor-specific as compared to currently used drugs, but also some of them are organ-specific. Some of such compounds have already passed the proof-of concept stage of development and have the therapeutic potential to determine the future of OAB pharmacotherapy. This review focuses on the mechanisms of substances that are now undergoing pre-clinical and clinical tests and their effects on the micturition cycle, while also identifying opportunities for using them with specific groups of patients. Due to the fact that OAB is a disease of symptoms and its aetiopathogenesis is complex, it seems that modern treatment methods should be tailor-made and based on the pathophysiological mechanisms that induce disease symptoms, rather than only treating the symptoms by inhibiting the contractility of the urinary bladder. PMID- 26848292 TI - Reduction in the level of antibodies against heat shock proteins 60 during different hormonal protocols in postmenopausal women. AB - INTRODUCTION: In current literature, the immune-inflammatory theory of atherosclerosis is widely discussed. The role of how heat shock proteins 60 (HSP60) lead to the development of the atheromatous plaque is especially underlined. The aim of the study is to estimate the influence of three hormonal protocols on behavior of antibodies against HSP60. It determines the state of endothelium in postmenopausal women. MATERIAL AND METHODS: The study was carried out on 90 women between 2007 and 2012. All the women were in their menopausal age (51 +/- 3 years), from the south region of Poland, with a follicle stimulating hormone (FSH) level above 25 mIU/ml, and with menopausal symptoms disturbing their normal daily activity. The study was done for a period of 6 months. Three groups of 30 randomized patients were formed. In the first group we used transdermal estrogen therapy in a 37.5 ug/24 h dose combined with a 10 mg dose of dydrogesterone. In the second group we applied transdermal estrogen therapy in a 50 ug/24 h dose with 2.5 mg of oral medroxyprogesterone. In both these groups, gestagens were administered continuously. In the third group, we prescribed continuous, oral, low-dose combined estrogen-gestagen therapy with 1 mg of ethinyl estradiol and 0.5 mg of norethisterone acetate. The control group consisted of 30 volunteers who were also from the south region of Poland, in good health, with menopausal symptoms, no menstrual period for the last 12 months, selected considering their age and weight, with an FSH level above 25 mIU/ml and with normal levels of thyroid stimulating hormone (TSH) and prolactin. All patients treated and in the control group were seronegative to Chlamydia pneumonia for the entire duration of the study. In the analysis conducted, nonparametric tests were used (Mann-Whitney U test, Wilcoxon test, Kruskal-Wallis test - ANOVA). RESULTS: After 6 months of hormonal therapy, we found that all schemes of treatment promote a significant reduction in antibodies against HSP60 in all treated groups vs. the control group. CONCLUSIONS: All of the investigated estrogen protocols have a favorable impact on the blood level of HSP60 antibodies in early postmenopausal women who have no cardiovascular risk factors. It triggers a better condition of endothelium. PMID- 26848290 TI - GC-MS metabolic profiling of Cabernet Sauvignon and Merlot cultivars during grapevine berry development and network analysis reveals a stage- and cultivar dependent connectivity of primary metabolites. AB - Information about the total chemical composition of primary metabolites during grape berry development is scarce, as are comparative studies trying to understand to what extent metabolite modifications differ between cultivars during ripening. Thus, correlating the metabolic profiles with the changes occurring in berry development and ripening processes is essential to progress in their comprehension as well in the development of new approaches to improve fruit attributes. Here, the developmental metabolic profiling analysis across six stages from flowering to fully mature berries of two cultivars, Cabernet Sauvignon and Merlot, is reported at metabolite level. Based on a gas chromatography-mass spectrometry untargeted approach, 115 metabolites were identified and relative quantified in both cultivars. Sugars and amino acids levels show an opposite behaviour in both cultivars undergoing a highly coordinated shift of metabolite associated to primary metabolism during the stages involved in growth, development and ripening of berries. The changes are characteristic for each stage, the most pronounced ones occuring at fruit setting and pre-Veraison. They are associated to a reduction of the levels of metabolites present in the earlier corresponding stage, revealing a required catabolic activity of primary metabolites for grape berry developmental process. Network analysis revealed that the network connectivity of primary metabolites is stage- and cultivar-dependent, suggesting differences in metabolism regulation between both cultivars as the maturity process progresses. Furthermore, network analysis may represent an appropriate method to display the association between primary metabolites during berry developmental processes among different grapevine cultivars and for identifying potential biologically relevant metabolites. PMID- 26848293 TI - Assessment of influence of pro-health nutrition education and resulting changes of nutrition behavior of women aged 65-85 on their body content. AB - INTRODUCTION: One of systemic changes connected to body ageing is the change of body content and the possibility of formation and/or intensification of insulin resistance, dyslipidemia and hypertension symptoms. MATERIAL AND METHODS: The research was conducted on 68 women aged 65-85 with body mass index (BMI) of 25.3 to 44.5 kg/m(2) who have been educated for four months. The energy and nutritive value of 204 daily food rations (DFRs) was evaluated twice: first days of October and - after the diet correction and implementation of the basic rules - from the end of January. The measurements, anthropometric and body content (in 35 women under research) with the bio-impedance method was checked twice - before and after completing the education. RESULTS: After completing the education, there was a statistically significant increase in consumption of grain products, fermented milk products, potatoes, fruit and vegetables, as well as seeds of legumes. Consumption of meat and cold meats, sugar and sweets significantly decreased. In the course of education, an individual-specific decrease in body mass of the participants was noticed, which found its reflection in positive changes of the anthropometric indicators value. A significant decrease in fat content in bodies of women under research was also noticed, which was accompanied by a slight increase in fat-free body mass and water. CONCLUSIONS: The four-month pro-health education of women influenced changes in improper nutrition habits resulting in, besides the improvement of organism functions and well-being of women under research, body mass loss and changes in content of the body. PMID- 26848294 TI - The influence of a 12-week program of physical activity on changes in body composition and lipid and carbohydrate status in postmenopausal women. AB - INTRODUCTION: For years there have been studies on what kind of physical activity is optimal for maintaining proper health condition. Besides well known and approved endurance training of moderate intensity, an importance of interval exercise where short term, sudden intensification of work is performed at low endurance load is emphasized. The aim of the work was to assess the effects of a program of physical activity applied to postmenopausal women regarding improvement of their body composition and biochemical indices of lipid and carbohydrate status. MATERIAL AND METHODS: The program of physical activity contained 12-week trainings of Nordic walking (NW) and gymnastic-dance classes (G D). The intensity of effort during the NW training was at the level of 60% HRmax, whereas intensity of G-D exercises was selected based on a subjective assessment of effort according to the scale of American College of Sports Medicine. RESULTS: The 12-week program of physical activity resulted in statistically significant lowering of total cholesterol and low density lipoprotein (LDL) fraction levels. An increase in high density lipoprotein (HDL) cholesterol level was observed, whereas the values of triacylglycerols (TG) did not change. The average fasting blood glucose level decreased significantly. Similar changes were noted for the insulin level. The analysed body biometrical-structural indices did not change significantly. CONCLUSIONS: The applied 12-week program of physical activity without changes of dietary habits contributed to an improvement in plasma lipid profile and an increased insulin sensitivity, but it did not affect significantly body composition. PMID- 26848295 TI - Ovarian function and ovarian blood supply following premenopausal abdominal hysterectomy. AB - INTRODUCTION: The issue of conserving the ovaries at hysterectomy in premenopausal women with benign gynecologic disease has been the subject of considerable controversy. Some clinicians prefer prophylactic oophorectomy in premenopausal women during hysterectomy to prevent future development of malignant changes in conserved ovaries. Other clinicians prefer to conserve apparently normal ovaries, because bilateral oophorectomy in premenopausal women results in an abrupt imbalance, sudden onset of menopausal symptoms, decreased libido, increased cardiovascular risk and osteoporosis. MATERIAL AND METHODS: Two hundred and twenty multipara women (who had completed their families), with benign uterine pathology were included in this prospective study for abdominal hysterectomy with bilateral ovarian preservation. Pre-operative vaginal ultrasound, Doppler studies, diagnostic hysteroscopy and endometrial biopsy were done followed by laboratory studies including Anti-mullerian hormone (AMH), follicle stimulating hormone (FSH) and estradiol for all studied women. Doppler studies, AMH, FSH and estradiol were repeated 6 and 12 months post-operative for assessment of the ovarian function and ovarian blood supply after hysterectomy. RESULTS: Pre-operative AMH, FSH and estradiol of the studied women were statistically insignificant compared to AMH, FSH and estradiol 6 and 12 months post-operative. Twelve months post-operative right and left ovarian volumes (6.92 +/- 0.18 and 6.85 +/- 0.19 cm(3), respectively) were significantly larger than pre-operative right and left ovarian volumes (6.19 +/- 0.22 and 5.86 +/- 0.23 cm(3), respectively), and, 12 months post-operative right and left ovarian pulsatility indices (2.92 +/- 0.15 and 2.96 +/- 0.16 cm/s, respectively) were significantly lower than pre-operative right and left ovarian pulsatility indices (3.45 +/- 0.19 and 3.36 +/- 0.2 cm/s, respectively). Eight (3.6%) cases of the studied women developed an ovarian cyst 6 months after hysterectomy, 3 were spontaneously resolved and the remaining 5 (2.27%) cases underwent exploratory laparotomy. CONCLUSIONS: There is no evidence of ovarian dysfunction affecting conserved ovaries one year after hysterectomy in premenopausal women as evident by AMH, FSH and estradiol. Furthermore, an increased ovarian volume and reduced ovarian pulsatility indices indicate a possible increase in ovarian blood supply, and preserved non-compromised ovarian function. PMID- 26848296 TI - Assessment of selected perioperative parameters in patients undergoing laparoscopic and abdominal supracervical hysterectomy. AB - INTRODUCTION: Subtotal hysterectomy is a method of treatment of patients with mild changes in the uterine body. Laparoscopic methods are increasingly used in surgical gynaecology. One of the limitations of laparoscopy is the proper level of operating surgeon's training, which may be assessed with the use of the learning curve. The aim of the study was to compare data regarding the perioperative period in patients who underwent subtotal hysterectomy with the two methods, and to establish a learning curve for laparoscopic subtotal hysterectomy. MATERIAL AND METHODS: One hundred and twenty-seven patients qualified for subtotal hysterectomy due to mild disturbances in the uterine body participated in the study. The study was conducted at the Clinical Department of Gynaecology and Obstetrics of Fryderyk Chopin Provincial Specialist Hospital in Rzeszow in 2012-2013. RESULTS: The time of laparoscopic subtotal hysterectomy is longer than that of the classical surgical procedure. Uterine myomas are the main indication for subtotal hysterectomy. Laparoscopic operation results in lower blood loss compared to the classical surgical method. The mean age of the patients operated due to mild changes in the uterine body is similar in both groups. Patients who are obese or have undergone Caesarean sections are more frequently qualified for the classical surgery. The study revealed a reduction in time of laparoscopic subtotal hysterectomy by ca. 31 minutes (33%). CONCLUSIONS: Laparoscopic subtotal hysterectomy is a method chosen by operating surgeons for patients with a lower perioperative risk. The period of the study made it possible to determine a learning curve for laparoscopic subtotal hysterectomy. PMID- 26848297 TI - Mediterranean diet for breast cancer prevention and treatment in postmenopausal women. AB - Breast cancer has become a big oncological concern both in Poland and most countries around the world. Epidemiological studies show that women who are directly in danger of suffering from breast cancer are mainly postmenopausal women. Due to the seriousness of the problem more attention is devoted to preventative measures that should be undertaken. That is why, Mediterranean diet and its beneficial effects on health started to be discussed. This diet contains antioxidants and shows anti-inflammatory properties which are crucial in breast cancer prevention. Its components are fish, olive oil, unrefined cereals, herbs, fruits and vegetables. In 1960s there was research done on the influence of low fat diet, as a preventative measure, on coronary artery disease. In 1980s, an interest in this diet grew and there was a great come-back to the origins of the diet. It led to estimation of its influence on cardiological and cancer diseases. Many positive effects were observed among people living in the Mediterranean area as far as health qualities of the diet are concerned. Mediterranean diet was compared with high fat diet of people living in Northern Europe and the USA. It seems to create new dietary recommendations as a preventative measure in breast cancer disease. The following article presents most recent data on the importance of Mediterranean diet as a prevention against breast cancer. PMID- 26848298 TI - Current clinical application of serum biomarkers to detect ovarian cancer. AB - For the last decades, hundreds of potential serum biomarkers have been assessed in diagnosing of ovarian cancer including the wide spectrum of cytokines, growth factors, adhesion molecules, proteases, hormones, coagulation factors, acute phase reactants, and apoptosis factors but except CA125 none of them have been applied to everyday clinical practice. Nowadays, the growing number of evidence suggests that the classic marker CA125 should be accompanied by HE4 and in fact, Risk of Ovarian Malignancy Algorithm (ROMA) is becoming more and more widespread in clinical practice for the evaluation of adnexal masses. Early ovarian cancer is often asymptomatic, so the challenge still exists to develop serum markers suitable for early diagnosis and screening. Current knowledge strongly points to different mechanisms of pathogenesis, genetic disturbances and clinical course of major histological subtypes of ovarian cancer. Thus, future biomarker/multimarker panels should take into consideration the implications of different molecular patterns and biological behavior of various subtypes of ovarian cancer. Very promising are studies on miRNAs - small non-protein coding gene-regulatory RNA molecules functionally involved in the pathogenesis of cancers acting as oncogenes (oncomirs) or tumor suppressors. The studies devoted to ovarian cancer tissue miRNA profiling have shown that miRNAs could be useful in diagnosing and predicting the OC outcome. They also confirmed that OC is a highly heterogeneous disease, gathering four distinct histological tumor subtypes characterized not only by distinct origin, behavior and response to chemotherapy but also by different patterns of miRNA expression. PMID- 26848299 TI - Association between estrogen levels and temporomandibular disorders: a systematic literature review. AB - INTRODUCTION: To evaluate whether the hypothesis that estrogen levels are associated with temporomandibular disorders (TMD) in humans can be confirmed or contradicted by available literature. MATERIAL AND METHODS: A systematic review based on the content of PubMed, Scopus, and Cochrane Library databases was performed. Studies were identified using a combination of key words 'temporomandibular disorder' and 'estrogen'. Nine studies were included into our review. RESULTS: The relationship between estrogen levels and TMD was found in seven out of nine reviewed papers. Results from two papers suggest that a high estrogen level is associated with an increased prevalence of TMD. Five additional papers found a relationship between a low estrogen level and an increase in TMD pain. In considering the value of evidence and inconsistencies of results in the reviewed publications, we state that there is weak evidence to support the hypothesis that estrogen levels are associated with TMD. CONCLUSIONS: Results of reviewed studies were divergent and sometimes contradictory. One possible explanation is that estrogen influences TMD pain processing differently than temporomandibular joints (TMJ) structures, as shown in many animal studies. Estrogen may influence TMD pain processing differently than TMJ structures. We suggest consideration of the dual action of estrogen when planning future studies on its association with TMD. PMID- 26848300 TI - Clinical practice recommendations for quality of life assessment in patients with gynecological cancer. AB - Quality of life (QoL) is a multidimensional concept regarding self-assessment of patients' situation. Quality of life has not been clearly defined up to date, although it is clear that it is a subjective self-assessment that to a significant extent is determined by individual needs, beliefs, values, attitudes, which are changing with time. Health-related QoL comprises basic dimensions such as patients' performance status, physical, emotional, and social functioning, symptoms of the disease and adverse effects of treatment, spiritual (God and existential) and other dimensions. In women, the ovary, cervical, corpus uterus, vagina and vulva cancers deteriorate QoL by disease progression and consequences of treatment, also in cancer survivors. Common symptoms include the genito urinary system, the lower gastrointestinal tract and peripheral neuropathies induced by chemotherapy. In young women, QoL is impaired by infertility, sexual problems and menopause symptoms. An overview of QoL questionnaires used in oncology with special regard to patients with gynecological tumors was conducted. A screening tool for psychological state assessment of oncology patients (distress thermometer), the Edmonton Symptom Assessment System (ESAS) and modular approach of QoL assessment recommended by the EORTC (European Organization for the Research and Treatment of Cancer) were presented. Practical guidelines were proposed to assess appropriately QoL in patients with gynecological cancers who stay at in-patient gynecology units and those treated at home and in an ambulatory care setting. PMID- 26848302 TI - Hypertension in Chronic Glomerulonephritis. AB - Chronic glomerulonephritis (GN), which includes focal segmental glomerulosclerosis and proliferative forms of GN such as IgA nephropathy, increases the risk of hypertension. Hypertension in chronic GN is primarily volume dependent, and this increase in blood volume is not related to the deterioration of renal function. Patients with chronic GN become salt sensitive as renal damage including arteriolosclerosis progresses and the consequent renal ischemia causes the stimulation of the intrarenal renin-angiotensin-aldosterone system(RAAS). Overactivity of the sympathetic nervous system also contributes to hypertension in chronic GN. According to the KDIGO guideline, the available evidence indicates that the target BP should be <=140mmHg systolic and <=90mmHg diastolic in chronic kidney disease patients without albuminuria. In most patients with an albumin excretion rate of >=30mg/24 h (i.e., those with both micro-and macroalbuminuria), a lower target of <=130mmHg systolic and <=80mmHg diastolic is suggested. The use of agents that block the RAAS system is recommended or suggested in all patients with an albumin excretion rate of >=30mg/ 24 h. The combination of a RAAS blockade with a calcium channel blocker and a diuretic may be effective in attaining the target BP, and in reducing the amount of urinary protein excretion in patients with chronic GN. PMID- 26848301 TI - Microvesicles as a potential biomarker of neoplastic diseases and their role in development and progression of neoplasm. AB - Neoplastic diseases together with cardiovascular diseases are the most frequent causes of death in the Polish population. Cancers of reproductive organs with breast cancer are responsible for the highest morbidity and mortality in women suffering from neoplasm diseases. Asymptomatic dynamics of the development of a neoplasm and no deviations from the normal level of laboratory results contribute to the fact that malignant diseases are diagnosed too late. The aim of modern medicine is to diagnose cancer at the earliest stage, however, there is no sufficiently sensitive and specific biomarker which can be used for diagnostic, prognostic and therapeutic purposes. Cellular interactions play the main role in the development, angiogenesis and invasiveness of a tumor. Recent research suggests the possibility of microvesicles (MVs) involvement in communication between cells. The MVs ability to fuse with various cells is used in cell-to-cell contact. Microvesicles cargo may include growth factors, their receptors, protease, adhesion molecules, signaling molecules and the sequence of DNA, mRNA, and micro-RNA. Larger quantities of MVs released from neoplastic cells affect both the local environment and systematic range causing metastases and progression. The research on molecular mechanisms of MVs' release and the presence of characteristic oncogenes in blood of patients with neoplasms is being carried out. Confirmation of MVs presence in patients' serum can potentially serve as useful information for therapeutic purposes and as the biomarker of a neoplastic disease. PMID- 26848303 TI - High Water Intake and Progression of Chronic Kidney Diseases. AB - Impact of water intake on the courses of chronic kidney and urinary tract diseases, such as urolithiasis, urinary tract infections, chronic kidney diseases (CKD), autosomal dominant polycystic kidney diseases and bladder cancer, has recently been studied. It still remains controversial whether increased water intake slows the progression of CKD or not. However, high water intake suppresses plasma levels of arginine vasopressin (AVP), which is expected to be beneficial for the preservation of the kidney function. Previous studies suggest that water intake suppresses plasma levels of AVP, and high levels of AVP have been suggested to play deleterious roles in animal models of kidney disease. Moreover, recent epidemic of CKD of unknown origin, which was supposed to be related to the insufficient water intake and chronic volume depletion, has been reported in Central America, further suggesting that the suppression of AVP by sustained water intake might be beneficial in this CKD population. Indeed, the data from recent studies were consistent with the view that high water intake is associated with slower progression of CKD. However, contradictory findings also exist. The intriguing effects of increased urine volume in preserving the glomerular filtration rate in human patients with CKD require more large and well-designed randomized prospective clinical trials. PMID- 26848304 TI - A Case Report of Familial Renal Hypouricemia Confirmed by Genotyping of SLC22A12, and a Literature Review. AB - A 24-year-old male visited our hospital because of pain in both flanks. His biochemistry profile showed an elevated serum creatinine level and low serum uric acid level. History taking revealed that he had undertaken exercise prior to the acute kidney injury (AKI) event, and he stated that family members had a history of urolithiasis. His renal profile improved after hydration and supportive care during hospitalization. Although the patient was subsequently admitted again due to AKI, his status recovered with similar treatment. Since the diagnosis of the patient was familial renal hypouricemia with exercise-induced AKI, we performed genotyping of SLC22A12, which encodes human urate transporter 1. The diagnosis was confirmed by the detection of a homozygous mutation of W258X. We herein, report a case of familial renal hypouricemia confirmed by genotyping of SLC22A12, and review the relevant literature. PMID- 26848305 TI - Spinning-induced Rhabdomyolysis: Eleven Case Reports and Review of the Literature. AB - Non-traumatic exertional rhabdomyolysis (exRML) occurs in individuals with normal muscles when the energy supplied to the muscle is insufficient. Here, we report 11 cases of spinning-induced rhabdomyolysis and review related literature. Spinning is a kind of indoor bicycle sport. The 11 patients who were diagnosed with exRML and admitted to CHA Bundang Medical Center were female and their ages ranged from 15 to 46 years. Two to three days prior to the presentation, the patients had attended a spinning class for the first time. All the patients had been otherwise healthy without any known medical illnesses. They were successfully treated without any complications, except mild non-symptomatic hypocalcemia. However, in the literature, severe complications such as compartment syndrome or acute kidney injury had been reported in relation to exRML including spinning-induced rhabdomyolysis. This spinning exercise needs prior guidelines and specific warnings to prevent exertional rhabdomyolysis. PMID- 26848306 TI - Mass casualty incidents - time to engage. AB - Mass casualty incident continues to overwhelm medical systems worldwide. Preparedness for an MCI is a crucial requisite for the injured better outcome. The World Society of Emergency Surgery initiated a survey in regard to its senior member's personal and institutional preparedness for MCI. The results here in presented indicate that WSES should engage in a formatted and structured preparedness course for medical institutions and individuals."By all appearances it seems to be just another normal Saturday morning in the emergency department (ED). Patients occupy thirty out of the sixty beds; some awaits discharge, some awaits admission to the hospital. All of a sudden the squeaky voice of the red phone is tearing the air, the hard metal voice on the line is reporting of an explosion in the nearby train station, estimated number of casualties is 80. You ask for their estimated time of arrival, when you hear the first sirens of ambulances parking out of the ED; no answer was needed. PMID- 26848307 TI - Predictors of immune reconstitution inflammatory syndrome associated with Kaposi's sarcoma: a case report. AB - We present here a case of immune reconstitution inflammatory syndrome associated with Kaposi's sarcoma (KS-IRIS) developed in an AIDS patient two months after initiation of antiretroviral therapy (ART). Baseline characteristics of this IRIS KS case, within a cohort of 12 naive AIDS-KS patients, were analyzed. No statistically significant differences in CD4 cell counts, plasma HIV RNA load, KS clinical staging, human herpesvirus 8 (HHV8) antibody titers and HHV8 load in peripheral blood mononuclear cells and saliva were evidenced. HHV8 load in plasma was found to be significantly higher in the KS-IRIS patient (> 6 log10 genome equivalents/ml, p = 0.01, t-test) compared to the 11 patients with KS regression. This case highlights that measurement of HHV8 load in plasma may be useful to identify patients at risk for KS-IRIS, and that this parameter should be included in the design of larger studies to define KS-IRIS risk predictors. PMID- 26848308 TI - Compositional difference in antioxidant and antibacterial activity of all parts of the Carica papaya using different solvents. AB - BACKGROUND: Carica papaya is a well known medicinal plant used in the West and Asian countries to cope several diseases. Patients were advised to eat papaya fruit frequently during dengue fever epidemic in Pakistan by physicians. This study was conducted to establish Polyphenols, flavonoids and antioxidant potential profile of extracts of all major parts of the C. papaya with seven major solvents i.e. water, ethanol, methanol, n-butanol, dichloromethane, ethyl acetate, and n-hexane. RESULTS: TPC, TFC, antioxidant and antibacterial potential were determined using different aqueous and organic solvents in addition to the determination of trace element in leaves, pulp and peel of C. papaya. Total soluble phenolics and flavonoids were found in promising quantity (~66 mg GAE/g) especially in case of methanol and ethanol extracts. Antioxidant activity using DPPH free radical scavenging assay indicated leaves, bark, roots and pulp extracts showed >75.0 % scavenging potential while leaves and pulp showed 84.9 and 80.9 % inhibition of peroxidation, respectively. Reducing power assay showed leaves, pulp and roots extracts active to reduce Fe(3+) to Fe(2+) ions. The antibacterial study showed pulp extract is the best to cope infectious action of bacteria. CONCLUSION: This study was conducted to test the medicinal profile of all parts of C. papaya by extracting secondary metabolites with organic and aqueous solvents. Ethanol and methanol both were found to be the best solvents of choice to extract natural products to get maximum medicinal benefits and could be used to medicinal formulation against different infectious diseases.Graphical abstractMedicinal evaluation of different parts of C. papaya. PMID- 26848309 TI - Policies on sexual expression in forensic psychiatric settings in different European countries. AB - BACKGROUND: Sexual expression by forensic psychiatric patients is poorly researched. METHODS: Forensic experts representing 14 European countries were interviewed to explore the diverse ways in which sexual expression within forensic settings is handled. RESULTS: No country had a national policy, although many had local policies or shared practices. Progressive approaches to patient sexuality were evident in nine of the countries sampled. The UK appeared the most prohibiting and excluding, its protocols apparently based on risk aversion and lack of emphasis or consideration of patients' sexual needs. CONCLUSIONS: Uniform national policy supporting patients' sexual expression would provide significant improvements. PMID- 26848310 TI - Physical and chemical differences between one-stage and two-stage hydrothermal pretreated hardwood substrates for use in cellulosic ethanol production. AB - BACKGROUND: There are many different types of pretreatment carried out to prepare cellulosic substrates for fermentation. In this study, one- and two-stage hydrothermal pretreatment were carried out to determine their effects on subsequent fermentations. The two substrates were found to behave differently during fermentation. The two substrates were then characterized using physical and chemical parameters. RESULTS: The one-stage substrate was found to have higher carbohydrate content and lower lignin content. It exhibited a higher level of viscosity, a larger settled volume, and a slower settling time than the two stage substrate. It also showed higher polarity and reduced crystallinity. Glycome profiling showed physical differences between the two substrates, specifically pointing toward higher levels of pectin and hemicellulose in the one stage substrate (MS1112) as compared to the two-stage substrate (MS1107). CONCLUSIONS: We hypothesize that these physical and chemical differences between the substrates contribute to the differences seen during fermentation including: ethanol yield, ethanol titer, fermentation rate, fermentation completion time, mixing, and substrate solubilization. These findings can be used in optimizing pretreatment parameters to maximize ethanol conversion and overall process yield for hardwood substrates. PMID- 26848311 TI - CANPMR syndrome and chromosome 1p32-p31 deletion syndrome coexist in two related individuals affected by simultaneous haplo-insufficiency of CAMTA1 and NIFA genes. AB - BACKGROUND: Non-progressive cerebellar ataxia with mental retardation (CANPMR, OMIM 614756) and chromosome 1p32-p31 deletion syndrome (OMIM 613735) are two very rare inherited disorders, which are caused by mono-allelic deficiency (haplo insufficiency) of calmodulin-binding transcription activator 1 (CAMTA1) and, respectively, nuclear factor 1 A (NFIA) genes. The yet reported patients affected by mono-allelic CAMTA1 dysfunction presented with neonatal hypotonia, delayed and ataxic gait, cerebellar atrophy, psychological delay and speech impairment, while individuals carrying a disrupted NFIA allele suffered from agenesis/hypoplasia of the corpus callosum, ventriculomegaly, developmental delay and urinary tract abnormalities. Both disorders were not seen in one patient together before. RESULTS: In this study two related individuals affected by a complex clinical syndrome, characterized by cognitive, neurological and nephrological features were studied for the underlying genetic disorder(s) by molecular cytogenetics. The two individuals present dysmorphic facies, macrocephaly, generalized ataxia, mild tremor, strabismus, mild mental retardation and kidney hypoplasia. Moreover, neuro-radiological studies showed hypoplasia of corpus callosum. Genetic investigations revealed a paracentric inversion in the short arm of one chromosome 1 with breakpoints within CAMTA1 and NFIA coding sequences. CONCLUSIONS: To the best of our knowledge, this is the first report of two patients harboring the simultaneous mono-allelic disruptions and consequent haplo insufficiencies of two genes due to an inversion event. Disruption of CAMTA1 and NFIA genes led to neuro-psychological and nephrological dysfunctions, which comprised clinical features of CANPMR syndrome as well as chromosome 1p32-p31 deletion syndrome. PMID- 26848312 TI - Erratum to: Evolving hard problems: generating human genetics datasets with a complex etiology. AB - [This corrects the article DOI: 10.1186/1756-0381-4-21.]. PMID- 26848315 TI - Elucidating the Association between Trait Mindfulness and Alcohol Use Behaviors among College Students. AB - Trait mindfulness has been considered a protective factor against alcohol use behaviors; however, the specific trait mindfulness facets, the specific alcohol use behaviors, and the mechanism underlying this relationship remain unclear. The present study examined the relationship between specific trait mindfulness facets and specific alcohol use behaviors, and how cued alcohol cravings might mediate this relationship. High-risk, young adult, undergraduate social drinkers (n = 240, 75% Caucasian, 70% female, mean age 19.4 years) completed a series of questionnaires and reported their level of alcohol cravings following alcohol pictorial cue exposure. Trait mindfulness was associated with less problematic alcohol use (r = -0.19, p < 0.01), but was not associated with alcohol use quantity (r = -0.07, p = 0.30) and duration (r = -0.08, p = 0.21). Only acting with awareness was associated with all types of alcohol use behaviors-including less problematic alcohol use (beta = -0.18, p = 0.02), lower alcohol use quantity (beta = -0.16, p = 0.04), and shorter alcohol use duration (beta = -0.19, p = 0.02). Cued alcohol cravings mediated the negative associations of overall trait mindfulness (b = -0.50, p < 0.05) and acting with awareness (b = -0.32, p < 0.05) with problematic alcohol use, and the negative associations of acting with awareness with alcohol use quantity (b = -1.24, p < 0.05) and alcohol use duration (b = -0.34, p < 0.05). These findings suggest that the protective effect of trait mindfulness likely operates through reducing cued alcohol cravings and might be most specific to acting with awareness among college students, thus suggesting a differential role of separate trait mindfulness facets in this high risk group. PMID- 26848313 TI - The histone demethylase dKDM5/LID interacts with the SIN3 histone deacetylase complex and shares functional similarities with SIN3. AB - BACKGROUND: Regulation of gene expression by histone-modifying enzymes is essential to control cell fate decisions and developmental processes. Two histone modifying enzymes, RPD3, a deacetylase, and dKDM5/LID, a demethylase, are present in a single complex, coordinated through the SIN3 scaffold protein. While the SIN3 complex has been demonstrated to have functional histone deacetylase activity, the role of the demethylase dKDM5/LID as part of the complex has not been investigated. RESULTS: Here, we analyzed the developmental and transcriptional activities of dKDM5/LID in relation to SIN3. Knockdown of either Sin3A or lid resulted in decreased cell proliferation in S2 cells and wing imaginal discs. Conditional knockdown of either Sin3A or lid resulted in flies that displayed wing developmental defects. Interestingly, overexpression of dKDM5/LID rescued the wing developmental defect due to reduced levels of SIN3 in female flies, indicating a major role for dKDM5/LID in cooperation with SIN3 during development. Together, these observed phenotypes strongly suggest that dKDM5/LID as part of the SIN3 complex can impact previously uncharacterized transcriptional networks. Transcriptome analysis revealed that SIN3 and dKDM5/LID regulate many common genes. While several genes implicated in cell cycle and wing developmental pathways were affected upon altering the level of these chromatin factors, a significant affect was also observed on genes required to mount an effective stress response. Further, under conditions of induced oxidative stress, reduction of SIN3 and/or dKDM5/LID altered the expression of a greater number of genes involved in cell cycle-related processes relative to normal conditions. This highlights an important role for SIN3 and dKDM5/LID proteins to maintain proper progression through the cell cycle in environments of cellular stress. Further, we find that target genes are bound by both SIN3 and dKDM5/LID, however, histone acetylation, not methylation, plays a predominant role in gene regulation by the SIN3 complex. CONCLUSIONS: We have provided genetic evidence to demonstrate functional cooperation between the histone demethylase dKDM5/LID and SIN3. Biochemical and transcriptome data further support functional links between these proteins. Together, the data provide a solid framework for analyzing the gene regulatory pathways through which SIN3 and dKDM5/LID control diverse biological processes in the organism. PMID- 26848317 TI - Behcet's disease in black skin. A retrospective study of 50 cases in Dakar. AB - INTRODUCTION: Although Behcet's disease is well-documented in Eastern populations, epidemiologic data in Sub-Saharan African population is scarce. The aim of this study was to define the epidemiologic and therapeutic aspects as well as clinical course of Behcet's disease in African black population. RESULTS: The study included 50 patients with Behcet's disease. The average age was 32 (18-67) years. A total of 31 patients were men and 19 were women. Two patients had a positive family history of Behcet's disease. The oral and genital aphthous lesions were present in 100% of patients. The pathergy test was positive in 16 patients (32%). Following skin conditions were observed: pseudofolliculitis in 15 patients (30%), acneiform papules in 6 patients (12%), erythema nodosum in 4 patients (8%) and leg ulcers in one patient. Ocular involvement was reported in 22 patients (44%) and joint involvement in 20 patients (40%). Neurological abnormalities were noted in 12 patients (24%). Gastrointestinal involvement with wide and deep ulcerations in the ileocecal region was observed in a patient. As treatment, a combination of oral corticosteroids and colchicine was used in 97% of our patients. Thalidomide was introduced in 3 patients and anticoagulation treatment in 19 patients. Clinical improvement was noted in 25 patients (50%), recurrence in 14 patients (28%) and 3 patients were lost to follow (6%). CONCLUSION: The Behcet's disease is not uncommon in black skin and generally affects young adults. Severe aphthous ulcers of the oral cavity and genital area are the most consistent finding. PMID- 26848316 TI - Non-invasive diagnostic techniques in the diagnosis of squamous cell carcinoma. AB - Squamous cell carcinoma is the second most common cutaneous malignancy after basal cell carcinoma. Although the gold standard of diagnosis for squamous cell carcinoma is biopsy followed by histopathology evaluation, optical non-invasive diagnostic tools have obtained increased attention. Dermoscopy has become one of the basic diagnostic methods in clinical practice. The most common dermoscopic features of squamous cell carcinoma include clustered vascular pattern, glomerular vessels and hyperkeratosis. Under reflectance confocal microscopy, squamous cell carcinoma shows an atypical honeycomb or disarranged pattern of the spinous-granular layer of the epidermis, round nucleated bright cells in the epidermis and round vessels in the dermis. High frequency ultrasound and optical coherence tomography may be helpful in predominantly in pre-surgical evaluation of tumor size. Emerging non-invasive or minimal invasive techniques with possible application in the diagnosis of squamous cell carcinoma of the skin, lip, oral mucosa, vulva or other tissues include high-definition optical coherence tomography, in vivo multiphoton tomography, direct oral microscopy, electrical impedance spectroscopy, fluorescence spectroscopy, Raman spectroscopy, elastic scattering spectroscopy, differential path-length spectroscopy, nuclear magnetic resonance spectroscopy, and angle-resolved low coherence interferometry. PMID- 26848318 TI - Multifocal squamous cell carcinoma arising in a Favre-Racouchot lesion - report of two cases and review of the literature. AB - BACKGROUND: Favre-Racouchot syndrome (nodular cutaneous elastosis with cysts and comedones) is a cutaneous disease characterized by coexistence of cysts, comedones and elastotic nodules in actinically damaged skin, typically on the face. Ultraviolet radiation plays a significant role in the development of the disease. Unilateral lesions have been described. MAIN OBSERVATION: In this report we present two cases of squamous cell carcinoma arising in a unilateral Favre Racouchot plaque. Both patients, fair-skinned, elderly, with impaired immune function developed large, deep invasive tumors with perineural extension. CONCLUSIONS: Squamous cell carcinomas of large size and prominent invasive growth developing in immunocompromised individuals carry poor prognosis with regard to recurrence rate and metastasis. Manifestations of malignancy as described in this report, indicate the importance of close follow-up of patients with Favre Racouchot syndrome. PMID- 26848319 TI - Delayed hypersensitivity reaction to intralesional triamcinolone acetonide following treatment for alopecia areata. Intradermal testing. AB - BACKGROUND: Hypersensitivity reactions to intralesional corticosteroids are very rare and have been infrequently reported. Patch testing is considered the gold standard for diagnosing contact allergic dermatitis. However, intradermal testing is thought to be more accurate and sensitive in selected cases. MAIN OBSERVATION: We describe a case of a delayed hypersensitivity reaction to intralesional triamcinolone acetonide following the treatment of alopecia areata. Patch testing to triamcinolone was negative but intradermal testing with a small volume of the same reagent elicited a strong reaction. CONCLUSIONS: Patch testingmay be unsuccessful in detecting delayed reactions to intralesional corticosteroids. In such cases intradermal testing at a non-cosmetically sensitive sitemay be a useful diagnostic tool. PMID- 26848320 TI - Ichthyosis linearis circumflexa in a child. Response to narrowband UVB therapy. AB - BACKGROUND: Ichthyosis linearis circumflexa is a rare form of ichthyosis characterized by polycyclic and annular lesions which are bordered by a double edged scale. Netherton syndrome is a genodermatosis in which ichthyosis linearis circumflexa is accompanied by characteristic hair shaft abnormalities and atopic diathesis. Different treatment modalities such as emmolients, keratolytics, calcipotriene, topical corticosteroids, topical calcineurin inhibitors, systemic retinoids, phototherapy and photochemotherapy have been used with variable results. Topical therapies may result in considerable absorption because of the defective barrier function in ichthyosis linearis circumflexa/Netherton syndrome. MAIN OBSERVATION: A 12-year-old patient diagnosed as ichthyosis linearis circumflexa demonstrated considerable improvement with narrowband UVB phototherapy at the end of 30 sessions. CONCLUSION: Short-term narrowband-UVB may an effective treatment option in patients with ichthyosis linearis circumflexa/Netherton syndrome. PMID- 26848321 TI - A rapidly growing giant cutaneous horn on the chest. AB - BACKGROUND: A giant cutaneous horn (GCH) is a morphologic description of conical lesion with a dense, hyperkeratotic protrusion of more than 1 cm in height that resembles an animal horn but without its bony core. These can occur in association with benign, premalignant or malignant cutaneous diseases which can be determined by excision and histopathologic review of the base. A PubMed search (performed June 2015) revealed 54 cases of giant cutaneous horns in world literature. The most common site affected was the scalp followed by lip and leg. The commonest histological diagnosis found was squamous cell carcinoma followed by verruca vulgaris and trichilemmal horns. MAIN OBSERVATION: We present an 85 year-old Filipino female with a one year history of a rapidly growing skin lesion on her upper chest. This was excised fully and histological review of the base demonstrated a keratoacanthoma. CONCLUSIONS: This is the first known occurrence of a giant cutaneous horn on the chest. While giant cutaneous horns are more commonly associated with malignant lesions, differential diagnosis includes benign lesions such as keratoacanthomas. This differential can be considered in a rapidly growing lesion. Excision and histopathologic review of the base of a cutaneous horn are essential to guide potential further therapy. PMID- 26848322 TI - Photoletter to the editor: Subcutaneous ciliated Mullerian cyst. AB - Cutaneous ciliated cysts are benign lesions occurring primarily on the lower extremity of girls and young women. We present a case of a cutaneous ciliated Mullerian cyst arising in the lower leg of a 14-year-old girl, with brief discussion of etiology and diagnosis. This is a rare entity with approximately 50 cases in the literature. PMID- 26848323 TI - Photoletter to the editor: Response of linear porokeratosis to photodynamic therapy in an 11-year-old girl. AB - Porokeratoses are a group of different entities that belong to the skin keratinization disorders. From the histological point of view the main and common characteristic of these disorders is the presence of compact parakeratotic columns known as cornoid lamellae. All varieties should be carefully treated and followed-up because of the risk of developing malignant epithelial tumors. We report the successful response to photodynamic therapy (PDT) in a pediatric patient diagnosed with linear porokeratosis. PMID- 26848324 TI - Photoletter to the editor: Calcinosis cutis in a burn scar. AB - Calcinosis cutis is a rare condition characterized by the deposition of insoluble calcium salts in the skin and subcutaneous tissue. Dystrophic calcinosis cutis appears as a result of local tissue damage or abnormalities, such as alterations in extra-cellular matrix proteins or subcutaneous tissue with normal calcium and phosphate serum levels. It has been rarely described as a late complication of burns. Latency periods of 15-54 years have been reported. We describe the case of a 57-year-old man with dystrophic calcinosis cutis in a burn scar, which developed 42 years after the skin injury. The condition was successfully treated with surgical excision. PMID- 26848325 TI - Intranodal palisaded myofibroblastoma: a case report from an unusual site. AB - Intranodal palisaded myofibroblastoma is a rare lymph node benign tumor, of unknown pathogenesis. Although benign, this lesion is frequently confused with metastatic lesions, especially in atypical sites. We report a 39-year-old man with a history of testicular malignant mixed germ cell tumor, presented with abdominal painless mass. The computed tomography of the abdomen confirmed the presence of 180 * 140 mm2 mass in the retroperitoneum with lympadenopathy on the right measuring 20 x 15 mm. The patient underwent exploratory laparotomy, and a surgical exerese of the retroperitoneeum lymph node was made. Histological and immunohistochemical examination confirmed the diagnosis of intranodal palissaded myofibroblastoma. This entity has been previously described, only once, in retroperitoneal region. Despite to the rarity of this neoplasm, we discuss clinicopathologic features and differential diagnosis. PMID- 26848326 TI - [Atypical localization of myomas during surgery: report of two cases including one in an emergency context]. PMID- 26848328 TI - [Intra-sinusal maxillary pleomorphic adenoma: a rare entity]. PMID- 26848327 TI - [Systemic lupus erythematosus revealed by a diffuse interstitial pneumonia]. PMID- 26848329 TI - [Skin ulcers revealing microscopic polyangiitis]. PMID- 26848330 TI - [Charcot foot: a diagnosis not to ignore]. PMID- 26848331 TI - [The tree that hides the forest]. PMID- 26848332 TI - [Breast metastasis from medullary carcinoma of the thyroid]. PMID- 26848333 TI - [Pelvic calcifications: from benin to malignant]. PMID- 26848335 TI - [Pachymeningitis and Sjorgren syndrome]. PMID- 26848334 TI - Susceptibility pattern of uropathogens to ciprofloxacin at the Ghana police hospital. AB - INTRODUCTION: Reports of increasing resistance of uropathogens to antimicrobials is of global concern. Culture and drug susceptibility tests remain a vital guide to effective therapy. The aim of this study was to determine the susceptibility pattern of isolated uropathogens to ciprofloxacin at the Ghana Police Hospital. METHODS: A total of 705 mid-stream urine samples were collected from patients suspected of having urinary tract infection, and visited the Ghana Police Hospital's laboratory from December 2013 to March 2014. Samples were cultured and isolates identified by standard methods, after which isolates susceptibility to ciprofloxacin was determined. RESULTS: Prevalence of urinary tract infection among patients' whose samples were analyzed was 15.9%. Predominant uropathogens isolated were E. coli (46.4%), Coliform (41.1%) and Coliform spp. with Candida (6.2%). Other isolates were Pseudomonas spp. (2.7%), Salmonella spp. (1.8%), Candida spp. (0.9%) and Klebsiella spp (0.9%). The overall resistance among the top three isolated uropathogens to ciprofloxacin was 35.9%. Resistance pattern demonstrated by respective isolates to ciprofloxacin were: E. coli (38.5%), Coliform (54.3%), and Coliform spp. with Candida (15%). The other isolates showed 100% sensitivity. CONCLUSION: This study revealed a relatively high ciprofloxacin resistance among isolated uropathogens, hence, the need for prudent prescribing and use of ciprofloxacin in urinary tract infection management. PMID- 26848336 TI - [Brown spots to meditate]. PMID- 26848338 TI - [Acute intestinal obstruction by a chicken bone]. PMID- 26848337 TI - Management of Type 2 Diabetes Mellitus by Traditional Medicine Practitioners in Kenya--Key Informant Interviews. AB - INTRODUCTION: Worldwide, plant based medicines are increasing in popularity due to perceptions of safety and efficacy. Herbalists in Kenya are widely consulted for the management of many diseases including Type 2 Diabetes Mellitus (T2DM). This study investigated the level of knowledge of the herbalists in management of T2DM. METHODS: Purposive sampling was used to identify 4 herbalists working in the urban areas who actively manage T2DM. Key informant interviews were used to gather data about the management of T2DM. It was analyzed using a content thematic approach. RESULTS: Diverse management methods which included both pharmacological and non- pharmacological were noted. Glycemic control was assessed with the help of a glucometer. In addition, presenting signs and symptoms were key in diagnosing T2DM. The herbalists used various herbs, minerals and animals as medicinal sources. The drugs were dispensed as decoctions with excipients being added appropriately. Adverse effects were recorded. The herbalists acknowledged that patients use both herbal and allopathic medicine together. A level of record keeping was observed but patient follow-up was poor. The cost of the herbal drugs was perceived to be excessive. CONCLUSION: Some similarities exist in the management of T2DM between allopathic and traditional medicine practitioners. Training of herbalists is required to improve the quality of care given to patients. PMID- 26848339 TI - [Relapsing vascular purpura and Sjogren syndrome: what is the link?]. PMID- 26848340 TI - [A strange tongue]. PMID- 26848341 TI - [Osteonecrosis of the femoral condyles revealed by septic arthritis in systemic lupus erythematosus]. PMID- 26848342 TI - [Secondary drug toxiderma to acenocoumarol]. PMID- 26848343 TI - [Hemophagocytosis and disseminated intravascular coagulation in visceral leishmaniasis in adults: three new cases]. PMID- 26848344 TI - [Basal cell carcinoma of the face: about four cases reported in Madagascar]. PMID- 26848345 TI - Kaiy (traditional cautery) in Benghazi, Libya: complications versus effectiveness. AB - INTRODUCTION: The practice of Kaiy (Cautery) as a traditional therapy is not science based though it is widely practiced worldwide. In Libya, in particular, it is commonly used with no any report or publication to emphasis on its positive or negative impact. This work was undertaken to highlight the complications and disadvantages of kaiy in the Libyan societies as it seems to cause more harm than benefit for the patient. METHODS: We conducted a questionnaire-based survey in the period from the first of March to the end of April (two months) of the year 2013, on fifty patients who were collected from different hospitals in Benghazi city, and who had experienced Kaiy therapy for different diseases. RESULTS: We found that kaiy application is more common among non educated patients (30 patients, 60%). Most of patients (45 cases, 90%) followed their relatives' advice and that 32 cases (63.5%) did not improve and show undesirable manifestations and complications. CONCLUSION: This study has shown that Kaiy therapy is associated with considerable health risks; therefore, we recommend discouraging and restricting its application. PMID- 26848346 TI - [Severe amyotrophic and debilitating presentation of scleroderma in a male]. PMID- 26848347 TI - [Traumatic dislocation of the hip]. PMID- 26848348 TI - [Digestive telangiectasia revealing systemic sarcoidosis]. PMID- 26848349 TI - Incidental neuroendocrine tumor of the appendiceal base less than20 mm in diameter: is appendectomy enough? AB - The appendixis the second primary site for neuroendocrine tumors. The management of incidentelly discovered neuroendocrine tumor of the appendiceal base less than 20 mm in diameter is still controversal. The aim of this study was to discuss the management of such tumors. Three patients were operated on for acute appendicitis. Histopathologic examination of surgery specimens revealed neuroendocrine tumors of the appendiceal base less than 20 mm in diameter. Since no one presented with poor prognostic factors, no complementary right hemicolectomy was performed. No recurrence was observed. The existence of poorprognostic factors at histopathologic examination should indicate complementary right hemicolectomy for incidental neuroendocrine tumor of the appendiceal base less than 20 mm in diameter. PMID- 26848350 TI - [Sudden hearing loss revealing Vogt-Koyanagi-Harada syndrome]. PMID- 26848351 TI - [Cardiac tamponade: a rare manifestation of hypothyroidism]. PMID- 26848352 TI - [Papillary carcinoma on thyroglossal duct cyst: report of two cases]. PMID- 26848353 TI - [Association between sex hormones, bone remodeling markers and bone mineral density in postmenopausal women of Moroccan origin (cross-sectional study)]. PMID- 26848355 TI - [Determination of biological and entomological parameters of Anopheles gambiae sl in malaria transmission in Bandundu city, Democratic Republic of Congo]. PMID- 26848354 TI - Delayed entry to care by men with HIV infection in Kumasi, Ghana. AB - INTRODUCTION: In resource-limited settings, men may face considerable barriers to accessing HIV care as early interventions tend to focus on antenatal care settings. METHODS: We performed a retrospective chart review of all adult patients referred to Komfo Anokye Teaching Hospital HIV clinic in Kumasi, Ghana in 2011 to identify the differences in clinical and demographic variables by gender at presentation to care using two-sample t tests with adjusted variance and Wilcox rank sum tests for continuous variables and Pearson chi-squared tests for categorical variables. We also compared differences in clinical and demographic variables among men stratified by CD4 count at initiation of care in order to identify variables associated with later entry to care. RESULTS: Demographically, men were more likely to be older (men age 42 vs. 37, p<0.01), have a greater number of dependent children (1.8 v. 1.5, p = 0.04), to be living with or married to their partner (65.4% vs. 49.0%, p<0.01), and to have a higher level of education (tertiary education, 45.8% vs. 25.4%, p<0.01) than women. Clinically, men were more likely to have a lower CD4 count at entry to care (260 v. 311 cells/uL, p<0.01), to report clinical symptoms to the nurse during intake (p<0.01), and to have any history of alcohol use (p<0.01). CONCLUSION: Men in Ghana are accessing treatment at a later stage of their disease than women. Efforts to test and link men to care early should be intensified. PMID- 26848356 TI - [Brain abscess complicating congenital heart disease: report of 7 cases at the Abidjan Heart Institute]. PMID- 26848357 TI - [Evaluation of the results of cochlear implantation]. PMID- 26848358 TI - Leiomyoma: a case report of a rare benign tumor of the female urethra. AB - Leiomyoma is a benign smooth muscle tumor which is rarely found in urethra. It often appears in females during their reproductive age (from menarche to menopause); the mean age of their appearance is approximately 41 years. Less than 100 cases were reported in the literature. We hereby report a case of a 52-year old White woman who presented with complaints of dysuria and urinary tract infection. The mass was completely removed by transvaginal excision with a rim of normal tissue. Histopathological studies confirmed the urethral leiomyoma. The patient remained asymptomatic and there was no evidence of recurrence in the followup. PMID- 26848359 TI - [The cranio-cerebral wound in Oxycephaly: what precautions to take to treat it?]. PMID- 26848360 TI - Oral malignant melanoma: a rare case with unusual clinical presentation. AB - Primary Oral malignant melanoma is a rare tumor with an indigent prognosis. This is a case report of 47-year-old Sudanese female diagnosed as Oral malignant melanoma of the mandible with an unusual pattern of growth and clinical presentation. Furthermore, a possibility of intraosseous origin is suggested. PMID- 26848361 TI - [Disorders of hemostasis in surgical intensive care at the University Hospital Joseph Ravoahangy Andrianavalona Antananarivo]. PMID- 26848362 TI - [Hemorrhagic shock following a renal biopsy: report of a case]. PMID- 26848363 TI - [Adherence to treatment in chronic dermatosis: about 200 cases]. PMID- 26848364 TI - [Place of surgery in the treatment of breast cancer in women at University Hospital Yalgado Ouedraogo: about 81 cases]. PMID- 26848365 TI - Swine flu-have we learnt any lesson from the past? AB - The world has suffered the pandemics due to swine flu in the past. The present epidemic in India has claimed many lives. Even, after the first outbreak of swine flu in 2009 no concrete efforts are done to prevent this infection. There is an urgent need to take radical steps to prevent such epidemics. PMID- 26848366 TI - Harlequin color change in preterm infant. PMID- 26848367 TI - [Fibrolipoma of the thumb]. PMID- 26848368 TI - Rhabdomyosarcoma: a rapidly growing malignancy. PMID- 26848369 TI - Tracheostomy in Pediatric Intensive Care Unit: When and Where? AB - BACKGROUND: Tracheostomy was first observed in Egyptian drawings in 3600 BC and performed frequently during the 1800's diphtheria epidemic. OBJECTIVES: The aim of this study was to elucidate the indications, complications, mortality rate, and the effect of pediatric tracheostomy on length of PICU or hospital stay. MATERIALS AND METHODS: Demographic characteristics, diagnosis at admission, duration of ventilation of 152 patients were analyzed retrospectively. RESULTS: The most common tracheostomy indication was prolonged intubation. The mean duration of mechanical ventilation before tracheostomy was 23.8 days. Forty five percent of the tracheostomy procedures were performed at bedside. Neither the place nor the age had any effect on the development of complications (P = 0.701, P = 0.622). The procedure enabled 62% of the patients to be discharged from hospital. CONCLUSIONS: Tracheostomy facilitates discharge and weaning of mechanical ventilation. Although the timing of tracheostomy has to be determined for each individual patient, three weeks of ventilation seems to be a suitable period for tracheostomy. Tracheostomy can be performed at bedside safely but patient selection should be made carefully. PMID- 26848370 TI - Risk of Wheezing Attacks in Infants With Transient Tachypnea Newborns. AB - BACKGROUND: The most common reason of respiratory distress in the newborn is transient tachypnea of the newborn (TTN). There are some reports saying that TTN is associated with increased frequencies of wheezing attacks. OBJECTIVES: The aims of this study were to determine the risk factors associated with TTN and to determine the association between TTN and the development of wheezing syndromes in early life. MATERIALS AND METHODS: In a historical cohort study, we recorded the characteristics of 70 infants born at the Shohadaye Kargar Hospital in Yazd between March 2005 and March 2009 and who were hospitalized because of TTN in the neonatal intensive-care unit. We called their parents at least four years after the infants were discharged from the hospital and asked about any wheezing attacks. Seventy other infants with no health problems during the newborn period were included in the study as the control group. RESULTS: The rate of wheezing attacks in newborns with TTN was more than patients with no TTN diagnosis (P = 0.014). TTN was found to be an independent risk factor for later wheezing attacks (relative risk [RR] = 2.8). CONCLUSIONS: The most obvious finding of this study was that TTN was an independent risk factor for wheezing attacks. So long-term medical care is suggested for these patients who may be at risk, because TTN may not be as transient as has been previously thought. PMID- 26848371 TI - Submucosal Hemangioma of the Trachea in an Infant: Diagnosis and Follow-Up with 3D-CT/Bronchoscopy. AB - INTRODUCTION: Infantile hemangiomas of the airway are diagnosed at bronchoscopy as part of the investigation of stridor or other respiratory symptoms. Here, we present three-dimensional computed tomography (3D-CT)/bronchoscopy findings of submucosal subglottic hemangioma missed at bronchoscopy. CASE PRESENTATION: We report on the clinical usefulness of 3D-CT/bronchoscopy as the primary diagnostic tool and follow-up method in the evaluation of suspected airway infantile hemangiomas, especially when the hemangioma is the submucosal type. CONCLUSIONS: 3D-CT/bronchoscopy will reduce the need for invasive laryngoscopic studies and help to diagnose submucosal hemangiomas undetected on laryngoscope. Additionally, 3D-CT/bronchoscopy will help evaluating the extent of the lesion, degree of airway narrowing, and treatment response. PMID- 26848372 TI - Factors Associated With Changes in Magnesium Levels in Asymptomatic Neonates: A Longitudinal Analysis. AB - BACKGROUND: Neonates and infants with hypomagnesemia present with seizures and psychomotor delay. OBJECTIVES: The present study evaluated the changes in magnesium (Mg) levels and factors associated with these in the first three days of life. MATERIALS AND METHODS: We monitored 50 clinically asymptomatic neonates; they were not given any magnesium supplements even if they had hypomagnesemia at baseline. The variables analysed were: serum Mg; gestational age; birth weight; length; and the ponderal index. We used random effects (RE) models for longitudinal analysis of these data. RESULTS: The mean standard deviation (SD) gestational age was 36.3 (3.6) weeks and the mean (SD) weight was 2604.2 (754.4) grams. About 31% of the neonates had hypomagnesemia (< 1.6 mg/dL) on day one; however, all had normal magnesium levels by day three of life (P < 0.001). At birth, after adjusting for intrauterine growth retardation status (IUGR), serum Mg levels were lower by 0.0097 mg/dL (95% CI: -0.019 to -0.0003) per 100 grams increase in weight of the neonate. After adjusting for IUGR status, the mean increase in the serum Mg levels was 0.14 mg/dL (95% confidence intervals [CI]: 0.10 to 0.18) per day. The per-day increase in magnesium levels was significantly higher in low birth weight babies (0.10, 95% CI: 0.01 to 0.18) compared with normal birth weight babies. CONCLUSIONS: Asymptomatic neonates may have a high prevalence of hypomagnesemia; however, the levels become normal without any magnesium supplementation. Even though regular monitoring of magnesium levels is useful, no supplements are required - particularly in clinically asymptomatic neonates. PMID- 26848373 TI - Evaluation oF Epicardial Fat and Carotid Intima-Media Thickness in Obese Children. AB - BACKGROUND: Epicardial fat has a role in cardiovascular diseases. OBJECTIVES: To assess epicardial fat and its relation with carotid intima-media thickness (IMT) in obese adolescents with metabolic syndrome (MetS). PATIENTS AND METHODS: The study included 60 obese adolescents and 25 control subjects. According to the presence or absence of MetS, obese subjects were divided into two subgroups. We measured weight, height, calculated Body Mass Index, waist circumference, hip circumference, systolic blood pressure, diastolic blood pressure and biochemical parameters (fasting glucose, total cholesterol, triglycerides, high density lipoprotein cholesterol, and low density lipoprotein cholesterol, High sensitivity C-reactive protein, fasting insulin, a homeostasis model assessment index of insulin resistance. plus an echocardiographic examination with measurement of epicardial adipose tissue thickness (EATT). RESULTS: Left ventricular mass index measurements were significantly higher in MetS group than both non-MS and control groups. The MetS and non-MetS obese patients had significantly higher carotid IMT in comparison to the control group. Carotid IMT measurements were significantly higher in MetS group had than both non-MetS and control groups. Also, EATT was significantly increased in patients with MetS compared to control group. Among MetS obese group, EATT was positively correlated with body mass index-standard deviation score, waist circumference, fasting glucose, fasting insulin, insulin resistance, triglyceride levels, left ventricular thickness, left ventricular mass index and myocardial performance index. EATT was found to be the only predictor of carotid IMT. CONCLUSIONS: EATT is closely related to carotid IMT and early cardiac dysfunction in obese adolescents with MetS. PMID- 26848374 TI - Evaluation of Neurodevelopment and Factors Affecting it in Children With Acyanotic Congenital Cardiac Disease. AB - BACKGROUND: The rate of congenital heart disease is 0.8% in all live births. The majority of this, however, is acyanotic congenital heart disease. The survival rate of children with cardiac disease has increased with the developments provided in recent years and their lifetime is extended. OBJECTIVES: This study aims to evaluate neurodevelopment of children with uncomplicated acyanotic congenital heart disease in preschool period and determine the factors affecting their neurodevelopmental process. PATIENTS AND METHODS: 132 children with acyanotic congenital heart disease aged 6 - 72 months were involved in the study. Mental development and intelligence levels of patients under 2 years old were assessed by using Bayley Development Scale-III, and Stanford Binet Intelligence test was employed for patients over 2 years old. Denver Developmental Screening Test II was applied to all patients for their personal-social, fine motor, gross motor and language development. RESULTS: The average age of patients (67 girls, 65 boys) included in the study was 35.2 +/- 19.6 months. It was determined that there were subnormal mental level in 13 (10%) patients and at least one specific developmental disorder in 33 (25%) patients. Bayley Mental Development Scale score of patients who had received incubator care in perinatal period was found significantly low (88 +/- 4.2) compared to those with no incubator care (93.17 +/ 8.5) (P = 0.028). Low educational level of father was established to be linked with low mental development scores at the age of 2 and following that age (P < 0.05). Iron deficiency anemia was discovered to be related to low psychometric test scores at every age (P < 0.05). CONCLUSIONS: Neurodevelopmental problems in children with acyanotic congenital heart disease were found higher compared to those in society. Mental development and intelligence levels of patients were determined to be closely associated with receiving incubator care, father's educational level and iron deficiency anemia. PMID- 26848375 TI - Evaluation of the Correlation Between tTG-IgA Titer and Duodenal Biopsy Findings in Children With Suspected Celiac Disease. AB - BACKGROUND: Celiac disease is an immune-mediated inflammation of the small intestine caused by sensitivity to dietary gluten in genetically sensitive individuals. OBJECTIVES: In this study, we aimed to evaluate the predictive value of tissue transglutaminase (tTG) antibodies for the diagnosis of celiac disease in a pediatric population in order to determine if duodenal biopsy can be avoided. PATIENTS AND METHODS: The subjects were selected among individuals with probable celiac disease, referring to a gastrointestinal clinic. After physical examinations and performing tissue transglutaminase-immunoglobulin A (tTG-IgA) tests, upper endoscopy was performed if serological titer was higher than 18 IU/mL. Therapy started according to pathologic results. RESULTS: The sample size was calculated to be 121 subjects (69 female and 52 male subjects); the average age of subjects was 8.4 years. A significant association was found between serological titer and pathologic results; in other words, subjects with high serological titer had more positive pathologic results for celiac disease, compared to others (P < 0.001). Maximum sensitivity (65%) and specificity (65.4%) were achieved at a serological titer of 81.95 IU/ml; the calculated accuracy was lower in comparison with other studies. As the results indicated, lower antibody titer was observed in patients with failure to gain weight and higher antibody titer was reported in diabetic patients. CONCLUSIONS: As the results indicated, a single serological test (tTg-IgA test) was not sufficient for avoiding intestinal biopsy. PMID- 26848376 TI - Saccharomyces Boulardii in Helicobacter Pylori Eradication in Children: A Randomized Trial From Iran. AB - BACKGROUND: Helicobacter pylori infects around 50% of the human population and is asymptomatic in 70% of the cases. H. pylori eradication in childhood will not only result in peptic symptoms relief, but will also prevent late-term complications such as cancer. Today, probiotics are being increasingly studied in the treatment of gastrointestinal infections as an alternative or complement to antibiotics. OBJECTIVES: In this study we aimed to assess the effect of S. boulardii supplementation on H. pylori eradication among children in our region. PATIENTS AND METHODS: In this randomized double-blind placebo-controlled clinical trial 28 asymptomatic primary school children with a positive H. pylori stool antigen (HpSA) exam were randomly allocated into the study group, receiving Saccharomyces boulardii, and the control group receiving placebo capsules matched by shape and size, for one month. The children were followed up weekly and were reinvestigated four to eight weeks after accomplished treatment by HpSA testing. The significance level was set at P < 0.05. RESULTS: 24 children completed the study. The mean HpSA reduced from 0.40 +/- 0.32 to 0.21 +/- 0.27 in the study group, indicating a significant difference (P = 0.005). However, such difference was not observed in the control group (P = 0.89). Moreover, the HpSA titer showed a 0.019 +/- 0.19 decrease in the study group whereas the same value was 0.0048 +/ 0.12 for the controls, again stating a significant difference (P = 0.01). CONCLUSIONS: Saccharomyces boulardii has a positive effect on reducing the colonization of H. pylori in the human gastrointestinal system but is not capable of its eradication when used as single therapy. PMID- 26848377 TI - Th1/Th2 Cytokine Profile and Its Diagnostic Value in Mycoplasma pneumoniae Pneumonia. AB - BACKGROUND: The levels of Th1/Th2 cytokine can alter in pathogenic infection in children with pneumonia. OBJECTIVES: To evaluate Th1/Th2 cytokine profile and its diagnostic value in M. pneumoniae pneumonia in children. PATIENTS AND METHODS: Children with M. pneumoniae mono-infection and 30 healthy children were tested with cytokines assay. We used real time PCR to detect M. pneumoniae in children with pneumonia. RESULTS: M. pneumoniae test was positive in 2188 (16.62%) out of 13161 pneumonia children. Children aged 5 - 9 years had the highest rate and summer was a season with high rate of M. pneumoniae incidence in Zhejiang province. During the course of study, in 526 pneumonia children with M. pneumoniae mono-infection and 30 healthy children cytokines assay was performed. IL-2 level of M. pneumoniae pneumonia children was lower than that of healthy children (median levels, pg/mL: IL-2: 3.2 vs. 5.7, P = 0.00), while IL-4, IL-10 and IFN-gamma were higher than in healthy children (median levels, pg/mL: IL-4: 3.2 vs. 1.5, P = 0.00; IL-10: 5.6 vs. 2.5, P = 0.001; IFN-gamma: 20.4 vs. 4.8, P = 0.001). CONCLUSIONS: IL-2 decreases and IL-4, IL-10 and IFN-gamma increase in children with M. pneumoniae pneumonia, which has a promising prospect in diagnosis of this disease in clinical practice. PMID- 26848378 TI - Pediatric Coronary Artery Revascularization Surgery: Development and Effects on Survival, Cardiac Events and Graft Patency for Children With Kawasaki Disease Coronary Involvements. AB - Pediatric coronary artery bypass surgery gained wide acceptance with the introduction of internal thoracic arteries (ITAs) for bypass operations for post Kawasaki disease (KD) lesions. The technique is now established as the standard surgical choice, and its safety even in infancy, graft patency, growth potential, graft longevity and clinical efficacy have been well documented. In this article the author reviews the development of pediatric coronary bypass as the main indication for the treatment of coronary lesions due to KD. I believe that coronary revascularization surgery in pediatric population utilizing uni- or bilateral ITAs is the current gold-standard as the most reliable treatment, although percutaneous coronary intervention with or without a stent has been tried with vague long-term results in children. PMID- 26848379 TI - Comparison Between Diuretic Urography (IVP) and Diuretic Renography for Diagnosis of Ureteropelvic Junction Obstruction in Children. AB - BACKGROUND: Ureteropelvic junction obstruction (UPJO) is one of the most common causes of urinary tract obstruction in children. Several methods are used to diagnose upper urinary tract obstruction including renal ultrasonography (US), intravenous pyelogram (IVP), diuretic renography (DR), magnetic resonance urography (MRU) and antegrade or retrograde pyelography. Nowadays it is suggested to use diuretic renography as the best method for diagnosing of UPJO. There is no comparative study between IVP and DR scan for diagnosis of UPJO in children. OBJECTIVES: The aim of the present study was to compare IVP with furosemide injection and diuretic renography in diagnosis of clinically significant UPJO. PATIENTS AND METHODS: This was a cross sectional study performed in 153 UPJO suspected children (121 boys, 32 girls) based on US findings in cases presented with urinary tract infection (UTI), prenatal hydronephrosis, abdominal/flank pain, abdominal mass and hematuria. Renal ultrasound was used as an initial screening tool for detection of urinary tract abnormality. Vesicoureteral reflux (VUR) was ruled out by voiding cystourethrography (VCUG). Serum creatinin, blood urea nitrogen, urinalysis and urine culture was screened in all cases. IVP with furosemide and DR were performed as soon as possible after the mentioned workup. RESULTS: During a five year period, 46 out of 153 patients were diagnosed as UPJO based on diuretic renography: the age ranged from 4 months to 13 years (mean: 3.1 +/- 0.78 years). There was a significant higher (76%) proportion of UPJO in the boys and in the left side (78%). The sensitivity of IVP with furosemide injection in diagnosis of UPJO was 91.3% whereas DR was accepted as standard for diagnostic procedure in diagnosis of UPJO. CONCLUSIONS: Although DR is accepted as the best method for diagnosis of UPJO, we found a small sensitivity difference between IVP and DR in kidneys with normal or near normal function. In many settings such as small cities lacking facilities for advanced isotope imaging technology, use of IVP with diuretic maybe an acceptable procedure for diagnosis of UPJO. PMID- 26848380 TI - The Outcome of Infantile Onset Pompe Disease in South of Iran. AB - BACKGROUND: Infantile Onset Pompe Disease (IOPD) is a rare autosomal recessive neuromuscular disorder. It is associated with cardiomegaly, hypotonia, paresis, and death in the first year of life. Since 2006, following the use of Alglucosidase alfa as Enzyme Replacement Therapy (ERT), the patients' survival is improved to a noticeable extent. OBJECTIVES: The purpose of this study is to examine the outcome of IOPD patients in South of Iran and the degree of responsiveness to ERT. PATIENTS AND METHODS: All patients who were diagnosed with IOPD on the bases of clinical symptoms, and enzyme assay on dried blood spot, were included in the study; and were followed up regarding cardiac function, locomotor activity, and cognition. RESULTS: Six patients with IOPD were identified. All these six patients suffered from Hypertrophic Cardiomyopathy (HCM). Four (67%) of them also had generalized hypotonia. Three patients expired during the first weeks due to severe respiratory infection. One of them also got involved with Acute Cardiopulmonary Failure while receiving the fifth dose of ERT; and expired. However, the remaining two patients had a significant improvement after the maximum of 117 weeks of following up both cardiac and locomotor findings. These two patients were the same patients who showed cardiac symptoms from the beginning but did not have generalized hypotonia. CONCLUSIONS: Although ERT has a significant effect on enhancing the survival of IOPD patients, it should be associated with meticulous heart-respiratory cares during the first months of treatment and preventing infection especially nosocomial infections. PMID- 26848381 TI - The Role of Mucosal Defense in Intestinal Injury of Infants With Fetal Growth Retardation. AB - BACKGROUND: Infants with fetal growth retardation (FGR) are prone to intestinal disorders. OBJECTIVES: Aim of the study was to determine the role of mucosal defense ability in formation of gut injury in infants with FGR. MATERIALS AND METHODS: 44 premature infants who were admitted to the Neonatal Intensive Care Unit were divided into two groups: 20 infants with FGR (FGR group) and 24 appropriate-for-gestational age newborns (AGA group). Control group consisted of 22 premature infants who were delivered after uncomplicated pregnancy. Gut barrier function was evaluated by detecting serum intestinal trefoil factor (ITF) and intestinal fatty acid binding protein (IFABP). The level of serum IFABP and ITF was measured by using ELISA method. RESULTS: FGR group showed significantly higher ITF concentration than AGA group on the first days of life (P ? 0.01). High level of ITF in the FGR group significantly declines up to 7th - 10th day of life (P ? 0.01). This reduction was accompanied by increase of IFABP which is a marker of ischemic intestinal mucosal injury. Correlation analyses showed that ITF had a negative correlation with IFABP. CONCLUSIONS: Infants with fetal growth retardation are characterized by a high level of ITF on the first days of life. This protects intestinal mucosa under hypoxic conditions. Its subsequent decline accompanied by an increase of IFABP reflects the depletion of Goblet cells to secret ITF causing damage to the integrity of intestinal mucosal barrier. PMID- 26848382 TI - Evaluation of Onlay Island Flap Technique in Shallow Urethral Plate Hypospadiasis. AB - BACKGROUND: Hypospadias is one of the most common congenital genital anomalies in males that necessitates to be operated early in infancy (when 6 to 9 months old). On the other hand, hypospadias is a challenging field of pediatric urology with multiple reconstruction techniques. A perfect hypospadias repair is supposed to return urethral continuity with sufficient caliber, eradicate phallus curvature, and supply an acceptable appearance with low complications. OBJECTIVES: This study aimed to evaluate the outcomes of using onlay island flap technique in the repair of hypospadias with shallow urethral plate. PATIENTS AND METHODS: In this prospective study within June 2012 to December 2013, we performed onlay island flap procedure to repair hypospadias with shallow urethral plate measuring less than 6 millimeter. This technique was selected for all types of hypospadiasis except subcoronal type. Nesbit's dorsal plication procedure was established for chordee. In cases with very small glans, urethroplasty was performed without glansplasty. RESULTS: Twenty three patients with mean age of 30 (range 10 - 60) months underwent onlay island flap repair; all had a shallow urethral plate < 6 mm, 3 had a very small glans, and 18 had chordee. Meatus was located in distal shaft in 5 cases, mid shaft in 8, proximal in 6 and penoscrotal type in 4 patients. Chordee was corrected with Nesbit's dorsal plication in 16 cases. Complications were: meatal stenosis in 2 cases and urethrocutaneous fistula in 2 patients, all of which were repaired surgically. Mean follow up time was 13 (3 - 20) months. All cases that had glansplasty have excellent esthetic appearance. CONCLUSIONS: This technique offers acceptable results regarding meatal stenosis, urethrocutaneous fistula and esthetic outcome. PMID- 26848383 TI - AAV vector encoding human VEGF165-transduced pectineus muscular flaps increase the formation of new tissue through induction of angiogenesis in an in vivo chamber for tissue engineering: A technique to enhance tissue and vessels in microsurgically engineered tissue. AB - In regenerative medicine, new approaches are required for the creation of tissue substitutes, and the interplay between different research areas, such as tissue engineering, microsurgery and gene therapy, is mandatory. In this article, we report a modification of a published model of tissue engineering, based on an arterio-venous loop enveloped in a cross-linked collagen-glycosaminoglycan template, which acts as an isolated chamber for angiogenesis and new tissue formation. In order to foster tissue formation within the chamber, which entails on the development of new vessels, we wondered whether we might combine tissue engineering with a gene therapy approach. Based on the well-described tropism of adeno-associated viral vectors for post-mitotic tissues, a muscular flap was harvested from the pectineus muscle, inserted into the chamber and transduced by either AAV vector encoding human VEGF165 or AAV vector expressing the reporter gene beta-galactosidase, as a control. Histological analysis of the specimens showed that muscle transduction by AAV vector encoding human VEGF165 resulted in enhanced tissue formation, with a significant increase in the number of arterioles within the chamber in comparison with the previously published model. Pectineus muscular flap, transduced by adeno-associated viral vectors, acted as a source of the proangiogenic factor vascular endothelial growth factor, thus inducing a consistent enhancement of vessel growth into the newly formed tissue within the chamber. In conclusion, our present findings combine three different research fields such as microsurgery, tissue engineering and gene therapy, suggesting and showing the feasibility of a mixed approach for regenerative medicine. PMID- 26848384 TI - The phenotypic impact of the male-specific region of chromosome-Y in inbred mating: the role of genetic variants and gene duplications in multiple inbred rat strains. AB - BACKGOUND: The male-specific region of chromosome-Y (MSY) contributes to phenotypes outside of testis development and has a high rate of evolution between mammalian species. With a lack of genomic crossover, MSY is one of the few genomic areas under similar variation and evolutionary selection in inbred and outbred animal populations, allowing for an assessment of evolutionary mechanisms to translate between the populations. METHODS: Using next-generation sequencing, MSY consomic strains, molecular characterization, and large-scale phenotyping, we present here regions of MSY that contribute to inbred strain phenotypes. RESULTS: We have shown that (1) MSY of rat has nine autosomal gene transposition events with strain-specific selection; (2) sequence variants in MSY occur with a 1.98 fold higher number of variants than other chromosomes in seven sequenced rat strains; (3) Sry, the most studied MSY gene, has undergone extensive gene duplications, driving ubiquitous expression not seen in human or mouse; (4) the expression profile of Sry in the rat is driven by the insertion of the Sry2 copy into an intron of the ubiquitously expressed Kdm5d gene in antisense orientation, but due to several loss of function mutations in the Sry2 protein, nuclear localization and transcriptional control are decreased; (5) expression of Sry copies other than Sry2 in the rat overlaps with the expression profile for human SRY; (6) gene duplications and sequence variants (P76T) of Sry can be selected for phenotypes such as high blood pressure and androgen receptor signaling within inbred mating; and most importantly, (7) per chromosome size, MSY contributes to higher strain-specific phenotypic variation relative to all other chromosomes, with 53 phenotypes showing both a male to female and consomic cross significance. CONCLUSION: The data presented supports a high probability of MSY genetic variation altering a broad range of inbred rat phenotypes. PMID- 26848385 TI - Are we overestimating the niche? Removing marginal localities helps ecological niche models detect environmental barriers. AB - Correlative ecological niche models (ENMs) estimate species niches using occurrence records and environmental data. These tools are valuable to the field of biogeography, where they are commonly used to infer potential connectivity among populations. However, a recent study showed that when locally relevant environmental data are not available, records from patches of suitable habitat protruding into otherwise unsuitable regions (e.g., gallery forests within dry areas) can lead to overestimations of species niches and their potential distributions. Here, we test whether this issue obfuscates detection of an obvious environmental barrier existing in northern Venezuela - that of the hot and xeric lowlands separating the Peninsula de Paraguana from mainland South America. These conditions most likely promote isolation between mainland and peninsular populations of three rodent lineages occurring in mesic habitat in this region. For each lineage, we calibrated optimally parameterized ENMs using mainland records only, and leveraged existing habitat descriptions to assess whether those assigned low suitability values corresponded to instances where the species was collected within locally mesic conditions amidst otherwise hot dry areas. When this was the case, we built an additional model excluding these records. We projected both models onto the peninsula and assessed whether they differed in their ability to detect the environmental barrier. For the two lineages in which we detected such problematic records, only the models built excluding them detected the barrier, while providing additional insights regarding peninsular populations. Overall, the study reveals how a simple procedure like the one applied here can deal with records problematic for ENMs, leading to better predictions regarding the potential effects of the environment on lineage divergence. PMID- 26848386 TI - Niche partitioning in a sympatric cryptic species complex. AB - Competition theory states that multiple species should not be able to occupy the same niche indefinitely. Morphologically, similar species are expected to be ecologically alike and exhibit little niche differentiation, which makes it difficult to explain the co-occurrence of cryptic species. Here, we investigated interspecific niche differentiation within a complex of cryptic bumblebee species that co-occur extensively in the United Kingdom. We compared the interspecific variation along different niche dimensions, to determine how they partition a niche to avoid competitive exclusion. We studied the species B. cryptarum, B. lucorum, and B. magnus at a single location in the northwest of Scotland throughout the flight season. Using mitochondrial DNA for species identification, we investigated differences in phenology, response to weather variables and forage use. We also estimated niche region and niche overlap between different castes of the three species. Our results show varying levels of niche partitioning between the bumblebee species along three niche dimensions. The species had contrasting phenologies: The phenology of B. magnus was delayed relative to the other two species, while B. cryptarum had a relatively extended phenology, with workers and males more common than B. lucorum early and late in the season. We found divergent thermal specialisation: In contrast to B. cryptarum and B. magnus, B. lucorum worker activity was skewed toward warmer, sunnier conditions, leading to interspecific temporal variation. Furthermore, the three species differentially exploited the available forage plants: In particular, unlike the other two species, B. magnus fed predominantly on species of heather. The results suggest that ecological divergence in different niche dimensions and spatio-temporal heterogeneity in the environment may contribute to the persistence of cryptic species in sympatry. Furthermore, our study suggests that cryptic species provide distinct and unique ecosystem services, demonstrating that morphological similarity does not necessarily equate to ecological equivalence. PMID- 26848387 TI - Urban gardens promote bee foraging over natural habitats and plantations. AB - Increasing human land use for agriculture and housing leads to the loss of natural habitat and to widespread declines in wild bees. Bee foraging dynamics and fitness depend on the availability of resources in the surrounding landscape, but how precisely landscape related resource differences affect bee foraging patterns remains unclear. To investigate how landscape and its interaction with season and weather drive foraging and resource intake in social bees, we experimentally compared foraging activity, the allocation of foragers to different resources (pollen, nectar, and resin) and overall resource intake in the Australian stingless bee Tetragonula carbonaria (Apidae, Meliponini). Bee colonies were monitored in different seasons over two years. We compared foraging patterns and resource intake between the bees' natural habitat (forests) and two landscapes differently altered by humans (suburban gardens and agricultural macadamia plantations). We found foraging activity as well as pollen and nectar forager numbers to be highest in suburban gardens, intermediate in forests and low in plantations. Foraging patterns further differed between seasons, but seasonal variations strongly differed between landscapes. Sugar and pollen intake was low in plantations, but contrary with our predictions, it was even higher in gardens than in forests. In contrast, resin intake was similar across landscapes. Consequently, differences in resource availability between natural and altered landscapes strongly affect foraging patterns and thus resource intake in social bees. While agricultural monocultures largely reduce foraging success, suburban gardens can increase resource intake well above rates found in natural habitats of bees, indicating that human activities can both decrease and increase the availability of resources in a landscape and thus reduce or enhance bee fitness. PMID- 26848388 TI - Basal bodies in Xenopus. AB - Xenopus has been one of the earliest and most important vertebrate model organisms for investigating the role and structure of basal bodies. Early transmission electron microscopy studies in Xenopus revealed the fine structures of Xenopus basal bodies and their accessory structures. Subsequent investigations using multiciliated cells in the Xenopus epidermis have further revealed many important features regarding the transcriptional regulation of basal body amplification as well as the regulation of basal body/cilia polarity. Future basal body research using Xenopus is expected to focus on the application of modern genome editing techniques (CRISPR/TALEN) to characterize the components of basal body proteins and their molecular functions. PMID- 26848390 TI - Renal sympathetic denervation using MR-guided high-intensity focused ultrasound in a porcine model. AB - BACKGROUND: Initial catheter-based renal sympathetic denervation (RSD) studies demonstrated promising results in showing a significant reduction of blood pressure, while recent data were less successful. As an alternative approach, the objective of this study was to evaluate the feasibility of using magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) to perform RSD in a porcine model. METHODS: An intravascular fiber optic temperature probe was used to confirm energy delivery during MRgHIFU. This technique was evaluated both in a vascular phantom and in a normotensive pig model. Five animals underwent unilateral RSD using MRgHIFU, and both safety and efficacy were assessed. MRI was used to evaluate the acoustic window, target sonications, monitor the near-field treatment region using MR thermometry imaging, and assess the status of tissues post-procedure. An intravascular fiber optic temperature probe verified energy delivery. Animals were sacrificed 6 to 9 days post-treatment, and pathological analysis was performed. The norepinephrine present in the kidney medulla was assessed post-mortem. RESULTS: All animals tolerated the procedure well with no observed complications. The fiber optic temperature probe placed in the target renal artery confirmed energy delivery during MRgHIFU, measuring larger temperature rises when the MRgHIFU beam location was focused closer to the tip of the probe. Following ablation, a significant reduction (p = 0.04) of cross sectional area of nerve bundles between the treated and untreated renal arteries was observed in all of the animals with treated nerves presenting increased cellular infiltrate and fibrosis. A reduction of norepinephrine (p = 0.14) in the kidney medulla tissue was also observed. There was no indication of tissue damage in arterial walls. CONCLUSIONS: Performing renal denervation non-invasively with MRgHIFU was shown to be both safe and effective as determined by norepinephrine levels in a porcine model. This approach may be a promising alternative to catheter-based strategies. PMID- 26848389 TI - Cilia in autophagy and cancer. AB - Cancer cells are distinguished from normal cells by increased proliferation and metabolism, loss of polarity control, and the potential to invade other tissues of the body. As hubs of signaling transduction, primary cilia have been linked to diverse developmental and degenerative disorders. Interestingly, loss of cilia has been observed in multiple malignant tumors, suggesting a potential suppressive role of cilia in cancer development. More recently, emerging studies began to unveil the bidirectional interaction of cilia and autophagy, a basic cellular clearance and recycling mechanism to regulate cell homeostasis. Here, we summarize the interplay between cilia and autophagy and discuss the roles of cilia in both autophagy and cancer. PMID- 26848391 TI - Minimizing eddy currents induced in the ground plane of a large phased-array ultrasound applicator for echo-planar imaging-based MR thermometry. AB - BACKGROUND: The study aims to investigate different ground plane segmentation designs of an ultrasound transducer to reduce gradient field induced eddy currents and the associated geometric distortion and temperature map errors in echo-planar imaging (EPI)-based MR thermometry in transcranial magnetic resonance (MR)-guided focused ultrasound (tcMRgFUS). METHODS: Six different ground plane segmentations were considered and the efficacy of each in suppressing eddy currents was investigated in silico and in operando. For the latter case, the segmented ground planes were implemented in a transducer mockup model for validation. Robust spoiled gradient (SPGR) echo sequences and multi-shot EPI sequences were acquired. For each sequence and pattern, geometric distortions were quantified in the magnitude images and expressed in millimeters. Phase images were used for extracting the temperature maps on the basis of the temperature-dependent proton resonance frequency shift phenomenon. The means, standard deviations, and signal-to-noise ratios (SNRs) were extracted and contrasted with the geometric distortions of all patterns. RESULTS: The geometric distortion analysis and temperature map evaluations showed that more than one pattern could be considered the best-performing transducer. In the sagittal plane, the star (d) (3.46 +/- 2.33 mm) and star-ring patterns (f) (2.72 +/- 2.8 mm) showed smaller geometric distortions than the currently available seven segment sheet (c) (5.54 +/- 4.21 mm) and were both comparable to the reference scenario (a) (2.77 +/- 2.24 mm). Contrasting these results with the temperature maps revealed that (d) performs as well as (a) in SPGR and EPI. CONCLUSIONS: We demonstrated that segmenting the transducer ground plane into a star pattern reduces eddy currents to a level wherein multi-plane EPI for accurate MR thermometry in tcMRgFUS is feasible. PMID- 26848392 TI - NOACs versus warfarin for stroke prevention in patients with AF: a systematic review and meta-analysis. AB - BACKGROUND: Warfarin has been the anticoagulant of choice for the prevention of ischaemic stroke in patients with atrial fibrillation (AF). Novel oral anticoagulants (NOACs) are increasingly used as an alternative. OBJECTIVES: The objective of this review was to evaluate the efficacy and safety of the NOACs versus warfarin in patients with AF. SEARCH METHODS: Medline, EMBASE and grey literature search for all phase II and III randomised control trials. DATA COLLECTION/ANALYSIS: Two authors independently reviewed abstracts and performed data extraction of eligible full-text articles. Revman V.5 was used for meta analysis. MAIN RESULTS: 12 studies were identified with a total study population of 77 011. NOACs demonstrated a reduction in the composite of stroke or systemic embolic events OR 0.85 (95% CI 0.75 to 0.98), a 52% reduction in intracranial haemorrhage OR 0.48 (95% CI 0.40 to 0.57) and a 14% reduction in mortality OR 0.86 (0.82 to 0.91). The 30-day end of study switch to warfarin demonstrated an in increase in stroke or systemic embolic events OR 2.60 (95% CI 1.61 to 4.18) and an increase in major bleeding OR 2.19 (95% CI 1.42 to 3.36). CONCLUSIONS: NOACs are superior to warfarin for the prevention of the composite of stroke and systemic embolism in patients with AF and an additional risk factor for stroke. There is a significant reduction in intracranial haemorrhage, which drives the finding of significantly lower mortality. During the poststudy switch from NOACs to warfarin there is an excess of the composite of stroke and systemic embolism as well as major bleeding events, which may be of significance in clinical practice. PMID- 26848393 TI - Prevalence and prognostic impact of kidney disease on heart failure patients. AB - OBJECTIVES: The aim was to determine the prevalence of different degrees of kidney dysfunction and to examine their association with short-term and long-term outcomes in a large unselected contemporary heart failure population and some of its subgroups. We examined to what extent the different cardiac conditions and their severity contribute to the prognostic value of kidney dysfunction in heart failure. DESIGN: We studied 47 716 patients in the Swedish Heart Failure Registry. Patients were divided into five renal function strata based on estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration equation. The adjusted association between kidney function and outcome was examined by Cox regression. RESULTS: 51% of the patients had eGFR <60 mL/min/1.73 m(2) and 11% had eGFR <30. There was increasing mortality with decreasing kidney function regardless of age, presence of diabetes, New York Heart Association NYHA class, duration of heart failure and haemoglobin levels. The risk HR (95% CI) persisted after adjusting for differences in baseline characteristics, severity of heart disease, and medical treatment: eGFR 60-89: 0.86 (0.79 to 0.95); eGFR 30-59: 1.13 (1.03 to 1.24); eGFR 15-29: 1.85 (1.67 to 2.07); and eGFR <15: 2.96 ([2.53 to -3.47)], compared with eGFR >=90. CONCLUSIONS: Kidney dysfunction is common and strongly associated with short-term and long-term outcomes in patients with heart failure. This strong association was evident in all age groups, regardless of NYHA class, duration of heart failure, haemoglobin level, and presence/absence of diabetes mellitus. After adjusting for differences in baseline data, aetiology and severity of heart disease and treatment, the strong association remained. PMID- 26848394 TI - Did the use of the Guideliner V2(TM) guide catheter extension increase complications? A review of the incidence of complications related to the use of the V2 catheter, the influence of right brachiocephalic arterial anatomy and the redesign of the V3(TM) Guideliner and clinical outcomes. AB - OBJECTIVE: We sought to investigate the incidence of complications associated with V2 Guideliner, understand the mechanisms and evaluate the impact of alterations made to the V3 Guideliner. METHODS: Retrospective analysis of consecutive cases employing V2 Guideliner from two university teaching hospitals. Complications were identified, analysed and classified into major versus minor ones. To understand the potential anatomical mechanism of these complications, analysis of normal great vessel anatomy was undertaken in separate cohort of patients undergoing cardiac catheterisation via right radial approach. Further analysis of consecutive cases employing V3 Gudieliner took place and the incidence of complications were compared between V2 and V3 groups. RESULTS: Total of 188 cases of V2 Guideliner use were identified. One major complication was reported (coronary dissection). Proximal collar interaction and stent damage occurred in 19 cases (10%). Anatomical data suggest that extending the V2 Guideliner tubing sited the proximal collar of the device in the brachiocephalic/subclavian artery, a potential site of tortuosity and potential cause of the Guideliner proximal collar-stent interaction. Further analysis of 124 cases of V3 Guideliner use demonstrated no cases with proximal collar-stent interactions, one case of longitudinal stent deformation and two incidents of stent interaction with the distal edge of the V3 Guideliner. CONCLUSIONS: We have demonstrated a higher incidence of V2 Guideliner complications compared to previous series. The change in design of the V2 Guideliner was a likely contributor but the modifications with V3 Guideliner appear to have ameliorated this issue. PMID- 26848395 TI - The relationship between oxidised LDL, endothelial progenitor cells and coronary endothelial function in patients with CHD. AB - OBJECTIVE: The balance between coronary endothelial dysfunction and repair is influenced by many protective and deleterious factors circulating in the blood. We studied the relationship between oxidised low-density lipoprotein (oxLDL), circulating endothelial progenitor cells (EPCs) and coronary endothelial function in patients with stable coronary heart disease (CHD). METHODS: 33 patients with stable CHD were studied. Plasma oxLDL was measured using ELISA, coronary endothelial function was assessed using intracoronary acetylcholine infusion and EPCs were quantified using flow cytometry for CD34(+)/KDR(+) cells. RESULTS: Plasma oxLDL correlated positively with the number of EPCs in the blood (r=0.46, p=0.02). There was a positive correlation between the number of circulating EPCs and coronary endothelial function (r=0.42, p=0.04). There was no significant correlation between oxLDL and coronary endothelial function. CONCLUSIONS: Plasma levels of oxLDL are associated with increased circulating EPCs in the blood of patients with CHD, which may reflect a host-repair response to endothelial injury. Patients with stable CHD had a high prevalence of coronary endothelial dysfunction, which was associated with lower numbers of circulating EPCs, suggesting a mechanistic link between endothelial dysfunction and the pathogenesis of atherosclerosis. PMID- 26848396 TI - High levels of cathepsin D and cystatin B are associated with increased risk of coronary events. AB - OBJECTIVE: The majority of acute coronary syndromes are caused by plaque ruptures. Proteases secreted by macrophages play an important role in plaque ruptures by degrading extracellular matrix proteins in the fibrous cap. Matrix metalloproteinases have been shown to be markers for cardiovascular disease whereas the members of the cathepsin protease family are less studied. METHODS: Cathepsin D, cathepsin L and cystatin B were measured in plasma at baseline from 384 individuals who developed coronary events (CEs), and from 409 age-matched and sex-matched controls from the Malmo Diet and Cancer cardiovascular cohort. RESULTS: Cathepsin D (180 (142-238) vs 163 (128-210), p<0.001), cathepsin L (55 (44-73) vs 52 (43-67), p<0.05) and cystatin B levels (45 (36-57) vs 42 (33-52), p<0.001) were significantly increased in CE cases compared to controls. In addition, increased cathepsin D (220 (165-313) vs 167 (133-211), p<0.001), cathepsin L (61 (46-80) vs 53 (43-68), p<0.05) and cystatin B (46 (38-58) vs 43 (34-54), p<0.05) were associated with prevalent diabetes. Furthermore, cathepsin D and cystatin B were increased in smokers. The HRs for incident CE comparing the highest to the lowest tertile(s) of cathepsin D and cystatin B were 1.34 (95% CI 1.02 to 1.75) and 1.26 (95% CI 1.01 to 1.57), respectively, after adjusting for age, sex, low-density lipoprotein/high-density lipoprotein ratio, triglycerides, body mass index, hypertension and glucose, but these associations did not remain significant after further addition of smoking to the model. In addition, cathepsin D was increased in incident CE cases among smokers after adjusting for cardiovascular risk factors. CONCLUSIONS: The associations of cathepsin D and cystatin B with future CE provide clinical support for a role of these factors in cardiovascular disease, which for cathepsin D may be of particular importance for smokers. PMID- 26848398 TI - Attribution of cause of end-stage renal disease among patients with systemic lupus erythematosus: the Georgia Lupus Registry. AB - OBJECTIVE: Whether using provider-attributed end-stage renal disease (ESRD) cause of systemic lupus erythematosus (SLE) in national surveillance data captures the entire population of patients with SLE and ESRD remains uncertain. Our goal was to examine attributed cause of ESRD in US surveillance data among patients with SLE who have developed ESRD. METHODS: Data from a national registry of treated ESRD (United States Renal Data System (USRDS)) were linked to the population based Georgia Lupus Registry (GLR). The provider-attributed cause of ESRD was extracted from the USRDS for each validated patient with SLE in the GLR (diagnosed through 2004) who initiated treatment for ESRD through 2012. The percentage of these patients with SLE whose ESRD was subsequently attributed to SLE in the USRDS was calculated, overall and by patient characteristics. RESULTS: Among 251 patients with SLE who progressed to ESRD, 78.9% had SLE as their attributed cause of ESRD. Of the remaining 53 patients, 43.4%, 18.9% and 15.6% had ESRD attributed to hypertension, diabetes mellitus type II and non-SLE related glomerulonephritis, respectively. Attribution of ESRD to SLE was higher among patients aged <=30 (87.9-93.9%) vs >30 (52.6%; p<0.001) but did not differ by sex or race. Having Medicaid (86.2%) or no insurance (93.5%) was associated with greater attribution of ESRD to SLE than having private insurance (72.5%; p=0.02), as was having two or more providers state a diagnosis of SLE (89.0% vs 73.5% with a rheumatologist diagnosis alone; p=0.008). CONCLUSIONS: These estimates indicate that USRDS-based studies may underreport ESRD among US patients with SLE. However, observed patterns of differential attribution of ESRD cause, particularly by age, suggest that providers may be correctly attributing ESRD to causes other than SLE among some patients with SLE. PMID- 26848397 TI - Risk factors for osteoporosis and fragility fractures in patients with systemic lupus erythematosus. AB - Osteoporosis (OP) and fragility fractures (FFx) are a known comorbidity in patients with systemic lupus erythematosus (SLE). This work aimed at evaluating (1) the prevalence of OP and FFx in a cohort of SLE and (2) the risk factors associated with both OP and FFx. The following data were collected from clinical charts: age, sex, menopausal status (MP), body mass index, smoking habits, disease duration, daily dose and cumulative glucocorticoids (GCs), type of organ involvement, comorbidities and medications. Data on bone metabolism, calcium and vitamin D supplementation and treatment with bisphosphonates, teriparatide or denosumab were collected, together with bone mineral density (BMD) values (measured by dual-energy X-ray absorptiometry (DXA)) and history of FFx (occurred after the onset of SLE and unrelated to trauma). OP and reduced BMD were defined according to the WHO. 186 patients were included (women 175, men 11; mean age 46.4+/-13 years, mean disease duration 14.9+/-9 years). At their last visit, 97 patients (52.2%) had a reduced BMD and 52 (27.9%) had OP. 22 patients (11.8%), all women, had at least one FFx; six patients (27.3%) were pre-menopausal. On univariate analysis, age, cumulative dose of GC, MP, therapy with antiepileptics and chronic renal failure (CRF) were correlated with OP (p<0.03); age, total amount of GC, MP, CRF, anticoagulants (AC) and antiepileptic therapy were correlated with FFx (p<0.05). The multivariate logistic model confirmed a direct association of OP and age, MP and antiepileptic therapy (p<=0.01) and of FFx and age, chronic therapy with AC and antiepileptics (p<0.03). In conclusion, low BMD is frequently observed in SLE, and FFx are observed also in premenopausal patients. Together with traditional risk factors (age, MP and GC), CRF and chronic treatments with AC or antiepileptics seem to be associated with a higher risk profile for OP and FFx occurrence. PMID- 26848399 TI - The association between diet and glucocorticoid treatment in patients with SLE. AB - BACKGROUND: Some studies suggest that the risk for and severity of systemic lupus erythematosus (SLE) can be modified by certain nutrients. The aim of this study was to investigate the association between diet and glucocorticoid (GC) treatment, as a proxy for disease activity, in patients with SLE. METHODS: We included 111 patients with SLE from the SLE Vascular Impact Cohort (SLEVIC). Dietary data were linked with data on GC treatment during a 2-year period. The association between diet and GC treatment was analysed with logistic regression. GC treatment and unchanged/increased doses were considered a proxy for active SLE. RESULTS: During the 2-year period, 54 patients (48.6%) had continued GC treatment. Dietary vitamin D was associated with GC treatment (OR=2.70-2.85 (95% CI 1.00 to 8.11)), whereas alcohol was inversely associated with GC treatment (OR=0.28-0.39 (95% CI 0.10 to 98)). Beta-carotene, fatty acid C18:2 and vitamin B6 were inversely associated with unchanged/increased GC dose (OR=0.29-0.30 (95% CI 0.10 to 0.90)). Finally, total energy intake was associated with GC doses >5.0 mg/day and >7.5 mg/day, explaining a direct association between 35 nutrients and higher GC dose levels (OR=2.98-23.82 (95% CI 1.01 to 203.88)). DISCUSSION: Dietary vitamin D did not protect against lupus activity. Beta-carotene, fatty acid C18:2 and vitamin B6 may protect against increased GC dose. The inverse association between alcohol intake and GC treatment/lupus activity may provide a partial explanation for the link between moderate alcohol intake and reduced risk of SLE. The association between higher dietary intake and higher GC dose levels indicated GC's influence on increasing appetite. PMID- 26848400 TI - Detecting and monitoring NO, SNO and nitrite in vivo. AB - The detection and quantification of nitric oxide and related reactive nitrogen species in vivo is vital to the understanding of the pathology and/or treatment of numerous conditions. To that end, several detection and quantification methods have been developed to study NO, as well as its redox relatives, nitrite and S nitrosothiols. While no single technique can offer a complete picture of the nitrogen cycle in a given system in vivo, familiarity with the benefits and limitations of several common tools for NOx determination can assist in the development of new diagnostics and therapeutics. PMID- 26848401 TI - Expert consensus on dynamics of laboratory tests for diagnosis of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis. AB - OBJECTIVE: To identify which laboratory tests that change over time are most valuable for the timely diagnosis of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA). METHODS: A multistep process, based on a combination of expert consensus and analysis of real patient data, was conducted. A panel of experts was first asked to evaluate 115 profiles of patients with MAS, which included the values of laboratory tests at the pre MAS visit and at MAS onset, and the change in values between the two time points. The experts were asked to choose the 5 laboratory tests in which change was most important for the diagnosis of MAS and to rank the 5 selected tests in order of importance. The relevance of change in laboratory parameters was further discussed and ranked by the same experts at a consensus conference. RESULTS: Platelet count was the most frequently selected test, followed by ferritin level, aspartate aminotransferase (AST), white cell count, neutrophil count, and fibrinogen and erythrocyte sedimentation rate. Ferritin was most frequently assigned the highest score. At the end of the process, platelet count, ferritin level and AST were the laboratory tests in which the experts found change over time to be most important. CONCLUSIONS: We identified the laboratory tests in which change over time is most valuable for the early diagnosis of MAS in sJIA. The dynamics of laboratory values during the course of MAS should be further scrutinised in a prospective study in order to establish the optimal cut-off values for their variation. PMID- 26848402 TI - Prevalence of rheumatic and musculoskeletal diseases and their impact on health related quality of life, physical function and mental health in Portugal: results from EpiReumaPt- a national health survey. AB - OBJECTIVES: To estimate the national prevalence of rheumatic and musculoskeletal diseases (RMDs) in the adult Portuguese population and to determine their impact on health-related quality of life (HRQoL), physical function, anxiety and depression. METHODS: EpiReumaPt is a national health survey with a three-stage approach. First, 10 661 adult participants were randomly selected. Trained interviewers undertook structured face-to-face questionnaires that included screening for RMDs and assessments of health-related quality of life, physical function, anxiety and depression. Second, positive screenings for >=1 RMD plus 20% negative screenings were invited to be evaluated by a rheumatologist. Finally, three rheumatologists revised all the information and confirmed the diagnoses according to validated criteria. Estimates were computed as weighted proportions, taking the sampling design into account. RESULTS: The disease specific prevalence rates (and 95% CIs) of RMDs in the adult Portuguese population were: low back pain, 26.4% (23.3% to 29.5%); periarticular disease, 15.8% (13.5% to 18.0%); knee osteoarthritis (OA), 12.4% (11.0% to 13.8%); osteoporosis, 10.2% (9.0% to 11.3%); hand OA, 8.7% (7.5% to 9.9%); hip OA, 2.9% (2.3% to 3.6%); fibromyalgia, 1.7% (1.1% to 2.1%); spondyloarthritis, 1.6% (1.2% to 2.1%); gout, 1.3% (1.0% to 1.6%); rheumatoid arthritis, 0.7% (0.5% to 0.9%); systemic lupus erythaematosus, 0.1% (0.1% to 0.2%) and polymyalgia rheumatica, 0.1% (0.0% to 0.2%). After multivariable adjustment, participants with RMDs had significantly lower EQ5D scores (beta=-0.09; p<0.001) and higher HAQ scores (beta=0.13; p<0.001) than participants without RMDs. RMDs were also significantly associated with the presence of anxiety symptoms (OR=3.5; p=0.006). CONCLUSIONS: RMDs are highly prevalent in Portugal and are associated not only with significant physical function and mental health impairment but also with poor HRQoL, leading to more health resource consumption. The EpiReumaPt study emphasises the burden of RMDs in Portugal and the need to increase RMD awareness, being a strong argument to encourage policymakers to increase the amount of resources allocated to the treatment of rheumatic patients. PMID- 26848403 TI - Psychological factors predict adherence to methotrexate in rheumatoid arthritis; findings from a systematic review of rates, predictors and associations with patient-reported and clinical outcomes. AB - Treatment response to methotrexate (MTX) for rheumatoid arthritis (RA) is not universal and non-adherence may partially explain this. The aims of this systematic review were to: (1) summarise existing rates of adherence to MTX, (2) identify predictors of adherence to MTX, and (3) assess the association between non-adherence and patient outcomes. The authors conducted a systematic search of papers published from January 1980 to February 2015 in PubMed, PsycINFO, EMBASE and CINAHL databases. Studies were eligible for inclusion if: (1) MTX was used as monotherapy or in combination with other therapies, (2) MTX was used in an RA or inflammatory polyarthritis population, (3) adherence was defined and measured as the extent to which patients followed their MTX regimen during the period of prescription, and (4) it was an original piece of research. In total, 10 studies met the inclusion criteria and 8 were evaluated as high quality. Rates of adherence ranged from 59% to 107%, and exposed differences in definitions of adherence, study methodologies and sample heterogeneity. A number of potential predictors of MTX adherence were identified; the strongest being related to beliefs in the necessity and efficacy of MTX, absence of low mood, mild disease and MTX monotherapy. Furthermore, 3 studies tested the association of adherence with disease activity as an outcome measure; all 3 found non-adherence associated with poor treatment response. This systematic review shows the importance of adherence to MTX treatment and summarises the associated modifiable factors. PMID- 26848404 TI - Crosstalk between adipose-derived stem cells and chondrocytes: when growth factors matter. AB - Adipose-derived stem cells (ASCs) and mesenchymal stem cells are promising for tissue repair because of their multilineage differentiation capacity. Our previous data confirmed that the implantation of mixed ASCs and chondrocytes into cartilage defects induced desirable in vivo healing outcomes. However, the paracrine action of ASCs on chondrocytes needs to be further elucidated. In this study, we established a co-culture system to achieve cell-to-cell and cell-to tissue crosstalk and explored the soluble growth factors in both ASCs and chondrocytes supplemented with 1% fetal bovine serum to mimic the physiological microenvironment. In ASCs, we screened for growth factors by semi-quantitative PCR and quantitative real-time PCR and found that the expression of bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor B (VEGFB), hypoxia inducible factor-1alpha (HIF-1alpha), fibroblast growth factor-2 (FGF-2), and transforming growth factor-beta1 significantly increased after co-culture in comparison with mono-culture. In chondrocytes, VEGFA was significantly enhanced after co-culture. Unexpectedly, the expression of collagen II and aggrecan was significantly down-regulated in the co-culture group compared with the mono culture group. Meanwhile, among all the growth factors screened, we found that the BMP family members BMP-2, BMP-4, and BMP-5 were down-regulated and that VEGFB, HIF-1alpha, FGF-2, and PDGF were significantly decreased after co-culture. These results suggest that crosstalk between ASCs and chondrocytes is a pathway through the regulated growth factors that might have potential in cartilage repair and regeneration and could be useful for tissue engineering. PMID- 26848405 TI - Principal Angle Enrichment Analysis (PAEA): Dimensionally Reduced Multivariate Gene Set Enrichment Analysis Tool. AB - Gene set analysis of differential expression, which identifies collectively differentially expressed gene sets, has become an important tool for biology. The power of this approach lies in its reduction of the dimensionality of the statistical problem and its incorporation of biological interpretation by construction. Many approaches to gene set analysis have been proposed, but benchmarking their performance in the setting of real biological data is difficult due to the lack of a gold standard. In a previously published work we proposed a geometrical approach to differential expression which performed highly in benchmarking tests and compared well to the most popular methods of differential gene expression. As reported, this approach has a natural extension to gene set analysis which we call Principal Angle Enrichment Analysis (PAEA). PAEA employs dimensionality reduction and a multivariate approach for gene set enrichment analysis. However, the performance of this method has not been assessed nor its implementation as a web-based tool. Here we describe new benchmarking protocols for gene set analysis methods and find that PAEA performs highly. The PAEA method is implemented as a user-friendly web-based tool, which contains 70 gene set libraries and is freely available to the community. PMID- 26848406 TI - miR-199b, a novel tumor suppressor miRNA in acute myeloid leukemia with prognostic implications. AB - BACKGROUND: Dysregulation of miRNAs that can act as tumor suppressors or oncogenes can result in tumorigenesis. Previously we demonstrated that miR-199b was significantly downregulated in acute myeloid leukemia (AML) and targets podocalyxin and discoidin domain receptor 1. Herein we investigated the functional role of miR-199b in AML and its prognostic implications. METHODS: Major approaches include transduction of hematopoietic stem cells and bone marrow transplantation, analyses of blood lineages, histone deacetylases (HDAC) inhibitors, and molecular and clinical data analyses of AML patients using The Cancer Genome Atlas (TCGA). RESULTS: We first examined the relative miR-199b expression in steady state hematopoiesis and showed CD33(+) myeloid progenitors had the highest miR-199b expression. Further, silencing of miR-199b in CD34(+) cells resulted in significant increases in CFU-GM colonies. Via TCGA we analyzed the molecular and clinical characteristics of 166 AML cases to investigate a prognostic role for miR-199b. The Kaplan-Meier curves for high and low expression values of miR-199b and the observed distribution of miRNA expression revealed the highly expressed group had significantly better survival outcomes (p < 0.016, log rank test). Additionally, there was significant difference between miR-199b expression across the AML subtypes with particularly low expression found in the FAB-M5 subtype. Furthermore, FAB-M5 subtype showed a poor prognosis with a 1-year survival rate of only 25 %, compared with 51 % survival in the overall sample (p < 0.024). Furthermore, significant inverse correlation of HoxA7 and HoxB6 expression with miR-199b was observed in FAB-M5 AML patients. Molecular mutations were analyzed among miR-199b high and low AML cases. Significant correlations in terms of association and survival outcomes were observed for NPMc and IDH1 mutations. Treatment of THP-1 cells (represents M5-subtype) with HDAC inhibitors AR-42, Panobinostat, or Decitabine showed miR-199b expression was significantly elevated upon AR-42 and Panobinostat treatment. To further understand the hematopathological consequences of decreased miR-199b, we employed a bone-marrow transduce/transplant (BMT) mouse model. Interestingly, in vivo miR-199b silencing per-se in HSCs did not result in profound perturbations. CONCLUSIONS: Loss of miR 199b can lead to myeloproliferation while HDAC inhibitors restore miR-199b expression and promote apoptosis. Low miR-199b in AML patients correlates with worse overall survival and has prognostic significance for FAB-M5 subtype. PMID- 26848407 TI - Stereotactic Radiosurgery for Glioblastoma. AB - Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and one of the most aggressive of all human cancers. GBM tumors are highly infiltrative and relatively resistant to conventional therapies. Aggressive management of GBM using a combination of surgical resection, followed by fractionated radiotherapy and chemotherapy has been shown to improve overall survival; however, GBM tumors recur in the majority of patients and the disease is most often fatal. There is a need to develop new treatment regimens and technological innovations to improve the overall survival of GBM patients. The role of stereotactic radiosurgery (SRS) for the treatment of GBM has been explored and is controversial. SRS utilizes highly precise radiation techniques to allow dose escalation and delivery of ablative radiation doses to the tumor while minimizing dose to the adjacent normal structures. In some studies, SRS with concurrent chemotherapy has shown improved local control with acceptable toxicities in select GBM patients. However, because GBM is a highly infiltrative disease, skeptics argue that local therapies, such as SRS, do not improve overall survival. The purpose of this article is to review the literature regarding SRS in both newly diagnosed and recurrent GBM, to describe SRS techniques, potential eligible SRS candidates, and treatment-related toxicities. In addition, this article will propose promising areas for future research for SRS in the treatment of GBM. PMID- 26848408 TI - Complete Resolution of Metastatic Gallbladder Cancer after Standard Gemcitabine Cisplatin Combination Therapy. AB - Gallbladder carcinoma (GBC) is a rare and deadly disease. The only curative option is a total surgical resection. If the disease is inoperable, palliative combination chemotherapy with gemcitabine-cisplatin remains the standard of care. We present here a case of a 47-year-old gentleman diagnosed with metastatic GBC who saw a complete resolution of his disease with seven cycles of standard gemcitabine-cisplatin chemotherapy. This case illustrates the importance of multidisciplinary care to explore all available options to provide optimal and tailored patient care. PMID- 26848409 TI - Dramatic Resolution of an Unresectable Giant Basal Cell Carcinoma Treated with Intensity-Modulated Radiation Therapy (IMRT) - A Case Report. AB - A 59-year-old man presented with an unresectable bulky giant basal cell carcinoma on his upper back. A trial of chemotherapy did not help relieve his symptoms or reduce the tumor. He was referred for and received definitive radiation therapy via IMRT with dramatic regression. The patient had been unable to lie on his back for many years but currently can sleep comfortably on his back without pain, which has dramatically improved his quality of life. PMID- 26848410 TI - High-Dose Radiation as a Dramatic, Immunological Primer in Locally Advanced Melanoma. AB - A 53-year-old white male presented with a right axillary melanoma that became widely metastatic and progressive despite multiple systemic treatments. He became refractory to ipilimumab (Yervoy) and pembrolizumab (Keytruda). He presented with a very large, painful left posterior neck mass that was 18 x 15 x 8 cm in size clinically. He was treated with a single fraction of 20 Gy using parallel opposed, spatially fractionated GRID radiation therapy (SFGRT), along with concurrent pembrolizumab. He also received 50 Gy in 25 fractions of conventional radiation. After five months of concurrent treatment, the refractory neck mass had completely resolved and he had no lasting side effects. Our dramatic case confirms the synergistic effect of high-dose GRID radiation as a primer for renewed, enhanced immunological response, and we have used this approach successfully on a number of similar patients with rapid and durable results. PMID- 26848411 TI - An Exceptionally Favorable Response to Etoposide and Cisplatin. AB - A 66-year-old female with multiple medical co-morbidities was diagnosed with limited-stage small cell lung carcinoma (SCLC) about 11 years ago, back in 2004. The patient was treated with concomitant chemotherapy and radiotherapy, along with prophylactic whole brain radiation. She received a total of four cycles of etoposide and cisplatin. The patient showed a complete response to the above mentioned treatment and had no evidence of tumor recurrence on any of the scans until 2015. Her last computed tomography (CT) scan of the chest in October 2015 showed bilateral hilar and mediastinal lymphadenopathy. Fine needle aspiration (FNA) of the left hilar node revealed the presence of malignant cells consistent with SCLC. Median survival for limited stage SCLC ranges from 16-24 months, and the reported five-year survival is 14%. In this report, we present the case of a 66-year-old female who showed an exceptionally favorable response to cisplatin and etoposide chemotherapy characterized by a disease-free survival of 11 years. PMID- 26848413 TI - An Unusual Recurrence of Signet Ring Cell Gastric Adenocarcinoma Treated by Right Hemicolectomy, Pancreaticoduodenectomy, and IVC Resection: Controversies and Dilemmas of Following Standard Treatment Pathways. AB - We present the case of a 67-year-old male patient with a past history of previously resected T3 right adrenocortical carcinoma and T3N1 signet ring cell adenocarcinoma of the stomach who presented with recurrence of gastric cancer in the form of a large solitary mass in the right abdomen. He was treated with ECX (epirubicin, cisplatin and capecitabine) chemotherapy and multivisceral resection. This recurrence pattern is the first such description in the literature, and we discuss the controversies and arguments in favour of offering surgical resection. PMID- 26848412 TI - Regression of Stage IV Pancreatic Cancer to Curative Surgery and Introduction of a Novel Ex-Vivo Chemosensitivity Assay. AB - Although data suggests little hope for survival when patients present with metastatic pancreatic cancer, recent advances in systemic therapy offer the possibility for dramatic tumor responses like those observed in other disease sites. Here, we present the case of a 50-year-old woman who presented with adenocarcinoma of the pancreas with two liver metastases and a CA 19-9 level of 1,659 U/mL. The patient received FOLFIRINOX (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) with a dramatic reduction in CA 19-9 level to 23.9 U/mL, and complete regression of both liver metastases. The patient then received capecitabine with the maintenance of a normal CA19-9 over the next 12 months. With no evidence of distant disease, concurrent systemic and local therapy with capecitabine-based chemoradiation (CapeXRT) was performed followed by observation for eight months with normal CA 19-9 readings. A mild increase in CA 19-9 (143 U/mL) prompted a restaging demonstrating an active primary tumor but no distant disease. Therefore, a pancreaticoduodenectomy (PD or Whipple) was performed rendering this patient free of detectable cancer. Our team has developed an ex vivo chemosensitivity assay in which the tumor tissue from an individual patient can be rapidly examined for sensitivity to available systemic therapy treatment strategies. We tested this patient's tumor for its sensitivity to gemcitabine (Gem) versus a combination of 5-fluorouracil, irinotecan, and oxaliplatin (FIRINOX). Remarkably, our assay confirmed a profound sensitivity of this patient's tumor to the agents she had received. PMID- 26848414 TI - Dramatic Response of a Large, 10 Cm Hepatocellular Carcinoma to Monotherapy with Yttrium-90 Based Selective Internal Radiation Therapy. AB - Hepatocellular carcinoma (HCC) is predominantly diagnosed in advanced stages and not amenable to surgical resection and transplantation. Systemic therapies have had a limited efficacy in treating HCC. Although HCC is a radiosensitive tumor, treatments with external-beam radiation are limited by radiosensitivity of normal liver tissue and surrounding organs-at-risk, i.e. bowel, stomach, and kidney. Several large retrospective series have demonstrated a modest effect of selective internal radiation therapy (SIRT) with Yttrium-90 ((90)Y) microspheres in unresectable HCC, both in terms of tumor response and survival. The authors present a patient with an extremely large, multifocal, unresectable HCC who achieved a dramatic response with SIRT treatment. PMID- 26848415 TI - Prolonged Response to an IGF-1 Receptor Antibody in a Patient with Metastatic Castration Prostate Cancer with Neuroendocrine Differentiation. AB - The androgen receptor is the main therapeutic target that has been successfully exploited through direct inhibition to extend survival of patients with metastatic castration-resistant prostate cancer (mCRPC). We present a patient who participated in a Phase II study of an antagonist antibody to insulin-like growth factor 1 receptor (IGF-1R) in men with mCRPC and experienced over five years of stable disease. His disease was rapidly progressing before exposure to the antibody and resumed its aggressive behavior following discontinuation of therapy, strongly supporting the attribution of his stable disease to IGF-1R inhibition. His pre-treatment biopsy exhibited increased protein expression of IGF-1R (and its downstream effector, phosphorylated-S6). Consequently, agents that target IGF-1R may provide profound and durable responses in a subset of patients and upfront molecular selection may enable us to identify those most likely to benefit. PMID- 26848416 TI - Recent Advances and Review on Treatment of Stiff Person Syndrome in Adults and Pediatric Patients. AB - Stiff Person Syndrome (SPS) is one of the rarest autoimmune neurological disorders, which is mostly reported in women. It is characterised by fluctuating muscle rigidity and spasms. There are many variants of SPS, these include the classical SPS, Stiff Leg Syndrome (SLS), paraneoplastic variant, gait ataxia, dysarthria, and abnormal eye movements. Studies have shown that the paraneoplastic variant of SPS is more common in patients with breast cancer who harbour amphiphysin antibodies, followed by colon cancer, lung cancer, Hodgkin's disease, and malignant thymoma. Currently, the treatment for SPS revolves around improving the quality of life by reducing the symptoms as far as possible with the use of GABAergic agonists, such as diazepam or other benzodiazepines, steroids, plasmapheresis, and intravenous immunoglobulin (IVIG). There have been random clinical trials with Rituximab, but nothing concrete has been suggested. A treatment approach with standard drugs and cognitive behavioral therapy (CBT) seems to be promising. PMID- 26848417 TI - Tranexamic Acid to Treat Life-threatening Hemorrhage in Prostate Cancer Associated Disseminated Intravascular Coagulation with Excessive Fibrinolysis. AB - This case illustrates the acute onset of life-threatening bleeding in a 57-year old male with treatment-resistant metastatic prostate cancer. Laboratory results confirmed the presence of disseminated intravascular coagulation (DIC). Despite aggressive transfusion support, his consumptive coagulopathy and persistent bleeding could not be controlled, and his need for blood products began to outpace the available supply. Our patient had declined further chemotherapy treatment for his underlying aggressive prostate cancer and would accept only palliative care. Both thrombosis and bleeding are known to coexist during DIC. In our patient, his hemorrhagic clinical condition and laboratory results supported the presence of DIC with an excessive fibrinolytic process in the setting of metastatic prostate cancer. Following careful consideration of potential risks and benefits, the decision was made to administer the antifibrinolytic agent tranexamic acid to control bleeding. Initiation of this treatment led to rapid bleeding cessation without thrombotic complication. Although controversial, this treatment was life-saving in our patient and allowed hospital discharge. He remained transfusion independent for his remaining four weeks of life following discharge, and ultimately died at home of multi-organ failure related to his cancer. PMID- 26848418 TI - Long-term Disease-free Survival Following Combination Multi-visceral and Metastatic Resection with Neoadjuvant FOLFIRINOX for Pancreatic Adenocarcinoma: A Case Report. AB - We describe a case of metastatic pancreatic adenocarcinoma treated with neoadjuvant FOLFIRINOX chemotherapy and combined pancreatic multi-visceral and metastatic liver resection in a patient currently disease-free four years after diagnosis. PMID- 26848419 TI - Leukemia Cutis of the Face, Scalp, and Neck Treated with Non-coplanar Split Field Volumetric Modulated Arc Therapy: A Case Report. AB - Malignancies with a superficial involvement of the scalp present a unique technical challenge for radiation treatment planning. As an example of this, leukemic infiltration of the superficial skin as the only presentation of the disease is a rare entity. For such cases, radiation oncologists have typically treated with 3D conformal radiotherapy with matched electron fields, a technique that can lead to significant dose inhomogeneity. In this report, we describe the case of a patient with leukemia cutis with a superficial involvement of the scalp, face, and shoulders that was treated with volumetric modulated arc radiotherapy, with an impressive clinical response. PMID- 26848420 TI - Multiple 'Brown Tumors' Masquerading as Metastatic Bone Disease. AB - 'Brown tumors' are known as 'osteitis fibrosa cystica' or 'Von Recklinghausen's disease' of the bone. A high index of suspicion is required by the treating doctor for diagnosing a 'brown tumor' in its early stage. Clinical suspicion, along with laboratory and radiological investigations, is required to diagnose this condition. We present a case of a 65-year-old woman who had multiple bony lesions and a thyroid nodule, which was initially considered as a metastatic bone disease, but later turned out to be 'brown tumors.' In all cases with multiple osteolytic lesions, a possibility of 'brown tumor' must be kept in mind. PMID- 26848421 TI - Unresectable Extraskeletal Myxoid Chondrosarcoma of the Neck: Early Tumor Response to Chemoradiotherapy. AB - Extraskeletal myxoid chondrosarcoma (EMC) rarely occurs in the head and neck and is generally managed with primary surgery. To our knowledge, no cases of unresectable EMC of the neck have been reported. We present a case of an unresectable EMC treated with chemotherapy and radiation, and highlight the exceptional early response to therapy. PMID- 26848422 TI - Ongoing Remission Nineteen Years after High-dose Chemotherapy for Oligometastatic Breast Cancer; What Can We Learn from this Patient? AB - Metastatic breast cancer is generally considered incurable. However, some patients show an exceptional response to treatment and enjoy long-term survival in good health. Here, we present a remarkable example of a patient who is still in remission 19 years after high-dose chemotherapy and locoregional treatment for limited oligometastatic breast cancer. We will outline our rationale for this treatment to explain her excellent response and suggest strategies to select larger patient groups that could similarly benefit from existing treatment approaches. PMID- 26848423 TI - Adult Brainstem Glioblastoma Multiforme: Long-term Survivor. AB - Adult, malignant brainstem gliomas are rare entities that often cause treatment conundrums due to the difficulty of surgical resection and, therefore, the absence of pathological diagnosis. This leads to a reliance on radiological imaging for diagnosis, which can often be unreliable. These shortcomings have made the treatment of brainstem gliomas challenging with unpredictable outcomes. The mainstay of treatment consists of chemotherapy and radiation; however, recurrence is inevitable. Predicting outcomes has been the major difficulty in treating these patients as adult malignant brainstem gliomas Grade II have a median survival between five to seven years while Grades III and IV are between 10-17 months (with some studies showing significantly longer survival in Grade III). Here, we present the case of a patient with the pathologic diagnosis of a right brachium pontis glioblastoma who had a remarkable survival of 73 months, whereas the expected median survival for these patients is 10-17 months. PMID- 26848424 TI - Green Campus initiative and its impacts on quality of life of stakeholders in Green and Non-Green Campus universities. AB - In 2010, Universitas Indonesia (UI) developed the UI GreenMetric World University Ranking for universities to share information about their sustainability practices. This ranking system was well aligned with the basis of Sustainability for Higher Education. The scoring system can also be used as a guideline for universities to achieve sustainability in their campuses. Since its first launch, more universities around the world have increasingly participated in the ranking system including many universities in Thailand. This study compared perception of stakeholders in Green Campus and Non-Green Campus universities in Thailand regarding stakeholders' satisfaction on sustainability practices and perceived quality of life at their campuses. The results showed that stakeholders at the studied Green Campus University were more satisfied and had significantly better perceived quality of life compared to stakeholders from the studied Non-Green Campus university. The results suggested that universities should adopt the criteria set in the UI GreenMetric World University Ranking to achieve better sustainability in their campuses and improve quality of life of their stakeholders. PMID- 26848425 TI - Axillary surgery in women with sentinel node-positive operable breast cancer: a systematic review with meta-analyses. AB - Traditionally, women with node-positive operable breast cancer have received complete axillary lymph node dissection (ALND), which is associated with significant morbidity, but recently less invasive alternatives have been explored. We conducted a systematic review of randomised controlled trials assessing alternative approaches to axillary surgery in patients with pathologically-confirmed sentinel node-positive operable breast cancer. We searched on 16/3/15 the Specialized Register of the Cochrane Breast Cancer group; CENTRAL; MEDLINE; PreMEDLINE; EMBASE; WHO International Clinical Trials Registry Portal; ClinicalTrials.gov; conference proceedings from ASCO and the San Antonio Breast Cancer meetings; checked reference lists and contacted authors to identify relevant studies. Double, independent study sifting, extraction, appraisal and summarising were undertaken using standard Cochrane Collaboration methodology. We included three studies (2020 patients) comparing ALND with sentinel lymph node dissection (SLND) to SLND alone, and two studies (1899 patients) comparing ALND to axillary radiotherapy (aRT). No differences in survival or recurrence were observed between ALND and SLND or aRT, but morbidity may have been increased in ALND, and all the results were subject to different biases, such as recruitment bias, performance bias, and outcome-reporting bias. Whilst it is encouraging that there appears to be no adverse effect on recurrence or survival, it will be appropriate to confirm these findings and provide additional data confirming quality of life effects and long term outcomes. PMID- 26848426 TI - A ratio chain-type exponential estimator for finite population mean using double sampling. AB - In this article, we have proposed a ratio chain-type exponential estimator for finite population mean of the study variable under double sampling scheme using auxiliary variables. The large sample properties of the suggested strategy are derived up to first order, of approximation, and its competence conditions are carried out under which the suggested estimator is performed better than the other existing estimators discussed in the literature. An empirical study shows that the suggested strategy is more efficient than the other relevant competing estimators under two phase sampling scheme. PMID- 26848427 TI - Epidemiological investigation of a foodborne outbreak in Spain associated with U.S. West Coast genotypes of Vibrio parahaemolyticus. AB - We describe an outbreak of seafood-associated Vibrio parahaemolyticus in Galicia, Spain in on 18th of August 2012 affecting 100 of the 114 passengers travelling on a food banquet cruise boat. Epidemiological information from 65 people was available from follow-on interviews, of which 51 cases showed symptoms of illness. The food items identified through the questionnaires as the most probable source of the infections was shrimp. This product was unique in showing a statistically significant and the highest OR with a value of 7.59 (1.52-37.71). All the nine strains isolated from stool samples were identified as V. parahaemolyticus, seven were positive for both virulence markers tdh and trh, a single strain was positive for trh only and the remaining strain tested negative for both trh and tdh. This is the largest foodborne Vibrio outbreak reported in Europe linked to domestically processed seafood. Moreover, this is the first instance of strains possessing both tdh+ and trh+ being implicated in an outbreak in Europe and that a combination of strains represent several pathogenicity groups and belonging to different genetic variants were isolated from a single outbreak. Clinical isolates were associated with a novel genetic variant of V. parahaemolyticus never detected before in Europe. Further analyses demonstrated that the outbreak isolates showed indistinguishable genetic profiles with hyper virulent strains from the Pacific Northwest, USA, suggesting a recent transcontinental spread of these strains. PMID- 26848429 TI - Detection of fraudulent financial statements using the hybrid data mining approach. AB - The purpose of this study is to construct a valid and rigorous fraudulent financial statement detection model. The research objects are companies which experienced both fraudulent and non-fraudulent financial statements between the years 2002 and 2013. In the first stage, two decision tree algorithms, including the classification and regression trees (CART) and the Chi squared automatic interaction detector (CHAID) are applied in the selection of major variables. The second stage combines CART, CHAID, Bayesian belief network, support vector machine and artificial neural network in order to construct fraudulent financial statement detection models. According to the results, the detection performance of the CHAID-CART model is the most effective, with an overall accuracy of 87.97 % (the FFS detection accuracy is 92.69 %). PMID- 26848428 TI - Modeling the influence of Twitter in reducing and increasing the spread of influenza epidemics. AB - A more realistic mathematical influenza model including dynamics of Twitter, which may reduce and increase the spread of influenza, is introduced. The basic reproductive number is derived and the stability of the steady states is proved. The existence of Hopf bifurcation are also demonstrated by analyzing the associated characteristic equation. Furthermore, numerical simulations and sensitivity analysis of relevant parameters are also carried out. Our results show that the impact posed by the negative information of Twitter is not significant than the impact posed by the positive information of Twitter on influenza while the impact posed by the negative information of Twitter on the influenza virus is still extraordinary. PMID- 26848430 TI - Pleural effusion in a child with a ventriculoperitoneal shunt and congenital heart disease. AB - We present the unique case of an 8 month old infant who required extracorporeal membrane oxygenation (ECMO) after neonatal repair of tetralogy of Fallot. While on ECMO, he developed grade 3 intraventricular hemorrhage resulting in hydrocephalus requiring ventriculoperitoneal (VP) shunt placement at 5 months of life. He presented to cardiology clinic with a 2-month history of poor weight gain, tachypnea, and grunting and was found to have a large right sided pleural effusion. This was proven to be cerebrospinal fluid (CSF) accumulation secondary to poor peritoneal absorption with subsequent extravasation of CSF into the thoracic cavity via a diaphragmatic defect. After diaphragm repair, worsening ascites from peritoneal malabsorption led to shunt externalization and ultimate conversion to a ventriculoatrial (VA) shunt. This is the second reported case of VA shunt placement in a child with congenital heart disease and highlights the need to consider CSF extravasation as the cause of pleural effusions in children with VP shunts. PMID- 26848431 TI - Differential pain response at local and remote muscle sites following aerobic cycling exercise at mild and moderate intensity. AB - Physical exercise has been shown to inhibit experimental pain response in the post-exercise period. Modulation of the pain system may be differentiated between muscle sites engaging in contractile activity. The purpose of this study was to assess the pain response at remote and local muscle sites following aerobic exercise at different work intensities. Participants included 10 healthy and physically active males (mean age +/- SD, 21.2 +/- 3.4). Somatic pressure pain threshold (PPT) at the rectus femoris (local) and brachioradialis (remote) muscle site was measured at before (Pre), 5 min after (Post1), and 15 min after (Post2) aerobic cycling exercise at 70 and 30 % of peak oxygen uptake (VO2peak) performed on different occasions in a counterbalanced order, separated by minimum of 3 days interval. Repeated measures ANOVA for PPT reveals significant main effect for time (f = 3.581, p = 0.049, observed power = 0.588) and muscle site (f = 17.931, p = 0.002, observed power = 0.963). There was a significant interaction shown for exercise intensity by time (f = 11.390, p = 0.012, observed power = 0.790). PPT at rectus femoris following cycling exercise at 70 % of VO2peak reveals a significant increase between Pre-Post1 (p = 0.040). PPT for rectus femoris following cycling exercise at 30 % of VO2peak revealed a significant decrease between Pre-Post1 (p = 0.026) and Pre-Post2 (p = 0.008). The PPT for brachioradialis following cycling exercise at 30 % of VO2peak revealed a significant decrease between Pre-Post1 (p = 0.011) and Pre-Post2 (p = 0.005). These results show that aerobic exercise increases PPT locally at the exercise muscle site following exercise at 70 % of VO2peak but reduces PPT following exercise at 30 % of VO2peak. PMID- 26848432 TI - Analysis of the antibacterial effect of an Edwardsiella tarda LuxS inhibitor. AB - LuxS/AI-2 quorum sensing is involved in the virulence of many bacterial pathogens, including the fish pathogen Edwardsiella tarda. In a previous study, we identified a small peptide, 5906, which inhibits E. tarda LuxS activity by binding specifically to LuxS in a manner that probably prevents the formation of functional LuxS homodimer. In the present study, using Japanese flounder as the experimental animal, we analyzed the antibacterial effect of 5906 produced by DH5alpha/p5906 (an Escherichia coli strain that produces 5906) and pID5906 (a mammalian plasmid that functional in flounder constitutively expresses 5906) against different bacterial fish pathogens. We found that fish administered with both DH5alpha/p5906 and pID5906 exhibited reduced bacterial recovery following E. tarda challenge. We also examined the effect of 5906 on the infection caused by another two fish pathogen, Aeromonas hydrophila and Vibrio harveyi. The results indicated that 5906 produced by DH5alpha/p5906 inhibited the AI-2 activity of A. hydrophila and V. harveyi, and that fish administered with DH5alpha/p5906 showed enhanced resistance against challenges with both bacteria. These results suggest that 5906 or its analogues/derivatives may be exploited for the development of broad-spectrum antibacterial agents applied in the prevention and control of fish bacterial diseases. PMID- 26848433 TI - Differences in sedentary time and physical activity among mothers and children using a movement-to-music video program in the home environment: a pilot study. AB - Measured objectively, less than a quarter of adults and under half of preschool children in Finland meet the physical activity recommendations. Moreover, higher sedentary time among parents (such as watching television) is associated with higher sedentary time of their children. The study introduces an intervention based on reducing sedentary behavior among mothers and their children. It utilizes a combination of music and exercise via a motivation-targeting movement to-music video program in the home environment. Data were collected in summer 2014 from Finland's Pirkanmaa region. Each mother-child pair (n = 24, child age: 4-7 years) was assigned to the intervention and control group. Both groups used an accelerometer and completed physical activity diaries for two consecutive weeks (14 days) during waking hours. In addition, the intervention group was instructed to use the movement-to-music video program during the second week. Differences between groups were expected in analysis of sedentary time and physical activity between weeks 1 and 2. The parameters assessed were sedentary time (i.e., lying down or sitting), standing still, and time spent in physical activity. Less sedentary time was revealed in week 2 than in week 1 among both intervention group mothers (56.6 vs. 53.3 %) and for intervention group children (49.5 vs. 46.0 %). The opposite was true of control group mothers (52.1 vs. 52.4 %) and children (46.7 vs. 49.8 %). Within-group differences in mothers' sedentary time correlated moderately with the children's sedentary time (Spearman's r = 0.56). All groups exhibited slightly more standing in the second week than in week 1. Both sets of intervention participants also engaged in more light physical activity in week 2, with the opposite evident for the two control sets. In all groups, except the control children, the proportion of moderate to vigorous physical activity was higher in the second week than the first. The use of music and video content together may yield added benefits in efforts to reduce sedentary behavior and increase physical activity among mothers and their children in the home environment. PMID- 26848435 TI - Urologist led one-stop testicular clinic: the UK 'gold standard'. AB - Prompt diagnosis and early treatment for testicular cancer is vital. To help with this a one-stop, urologist run, testicular clinic with testicular ultrasound scanning as an integral part of the clinic format was introduced to investigate patients in an efficient and timely manner. The aim of this study was to assess the feasibility and efficiency of running a one-stop testicular clinic. A prospectively collected electronic database of all patients attending a one-stop testicular clinic at a busy university hospital was interrogated over a 6-year period. Only new referral males, above the age of 15 years old were included. Case notes were reviewed retrospectively. A total of 1757 patients were found with a median age of 36. 6.3 % had a suspicious ultrasound scan and overall 5.6 % were found to have malignancy histologically. In addition a significant proportion of men with a history of testicular maldescent went on to develop testicular cancer (p < 0.01). Median time from referral to clinic and clinic to orchidectomy for suspected testicular cancers was 9 and 5 days respectively (95 % CI). Some of the benefits of a urologist run one-stop testicular clinic include: timely diagnosis and treatment, early reassurance with normal investigations, the discovery of clinically unsuspecting malignancy and the increase in teaching opportunities. These collective benefits must improve patient experience and benefit the department as a whole. A urologist led one-stop testicular clinic should be regarded as the gold standard. PMID- 26848434 TI - Fascicle length does increase in response to longitudinal resistance training and in a contraction-mode specific manner. PMID- 26848436 TI - An application of extreme value theory to the management of a hydroelectric dam. AB - Assessing the probability of very low or high water levels is an important issue in the management of hydroelectric dams. In the case of the Akosombo dam, very low and high water levels result in load shedding of electrical power and flooding in communities downstream respectively. In this paper, we use extreme value theory to estimate the probability and return period of very low water levels that can result in load shedding or a complete shutdown of the dam's operations. In addition, we assess the probability and return period of high water levels near the height of the dam and beyond. This provides a framework for a possible extension of the dam to sustain the generation of electrical power and reduce the frequency of spillage that causes flooding in communities downstream. The results show that an extension of the dam can reduce the probability and prolong the return period of a flood. In addition, we found a negligible probability of a complete shutdown of the dam due to inadequate water level. PMID- 26848437 TI - Detection of group A rotavirus strains circulating among children with acute diarrhea in Indonesia. AB - Rotavirus is the major cause of severe diarrhea in children under 5 years old in developed and developing countries. Since improvements in sanitation and hygiene have limited impact on reducing the incidence of rotavirus diarrhea, implementation of a vaccine will be a better solution. We conducted an observational study to determine the disease burden and to identify the genotype of circulating rotavirus in Indonesia. Hospitalized children due to acute diarrhea were enrolled from four teaching hospitals in Indonesia. Stool samples were collected based on WHO protocol and were tested for the presence of group A rotavirus using enzyme immunoassay. Then, rotavirus positive samples were genotyped using RT-PCR. Fisher's Exact tests, Chi square tests and logistic regression were performed to determine differences across hospital and year in rotavirus prevalence and genotype distribution. There were 4235 samples from hospitalized children with diarrhea during 2006, 2009 and 2010. Among them, the rotavirus positive were 2220 samples (52.42 %) and incidence rates varied between hospitals. The G1P[8], G1P[6], and G2P[4] were recognized as the dominant genotypes circulating strains in Indonesia and the proportion of predominant strains changed by year. Our study showed the high incidence of rotavirus infection in Indonesia with G1P[8], G1P[6], and G2P[4] as the dominant strains circulating in Indonesia. These results reinforce the need for a continuing surveillance of rotavirus strain in Indonesia. PMID- 26848438 TI - Tradition and Future of the Korean Society of Plastic and Reconstructive Surgeons. PMID- 26848439 TI - Mandibular Reconstruction Using the Free Vascularized Fibula Graft: An Overview of Different Modifications. AB - The reconstruction of the mandible is a complex procedure because various cosmetic as well as functional challenges must be addressed, including mastication and oral competence. Many surgical techniques have been described to address these challenges, including non-vascularized bone grafts, vascularized bone grafts, and approaches related to tissue engineering. This review summarizes different modifications of the free vascularized fibula graft, which, since its introduction by Hidalgo in 1989, has become the first option for mandibular reconstruction. The fibula free flap can undergo various modifications according to the individual requirements of a particular reconstruction. Osteocutaneous flaps can be harvested for reconstruction of composite defects. 'Double barreling' of the fibula can, for instance, enable enhanced aesthetic and functional results, as well as immediate one-stage osseointegrated dental implantation. Recently described preoperative virtual surgery planning to facilitate neomandible remodeling could guarantee good results. To conclude, the free fibula bone graft can currently be regarded as the "gold standard" for mandibular reconstruction in case of composite (inside and outside) oral cavity defects as well as a way of enabling the performance of one-stage dental implantation. PMID- 26848441 TI - Outcomes of Surgical Treatment of Vascular Anomalies on the Vermilion. AB - BACKGROUND: The vermilion plays an important role in both the aesthetic and functional aspects of facial anatomy. Due to its structural features, the complete excision of vascular anomalies on the vermilion is challenging, making it difficult to determine the appropriate treatment strategy. Thus, the authors analyzed the results of surgical treatment of vascular anomalies on the vermilion. METHODS: The medical records of 38 patients with vascular anomalies on the vermilion who underwent surgery from 1995 to 2013 were analyzed. Nine of the cases had an involuted hemangioma, and 29 cases had a vascular malformation; of the vascular malformations, 13, 11, one, and four cases involved were capillary malformations (CMs), venous malformations (VMs), lymphatic malformations (LMs), and arteriovenous malformations (AVMs), respectively. We investigated the surgical methods used to treat these patients, the quantity of surgical procedures, complications and instances of recurrence, and self-assessed satisfaction scores. RESULTS: A total of 50 operations were carried out: 28 horizontal partial excisions, eight vertical partial excisions, and 14 operations using other surgical methods. All cases of AVM underwent complete excision. Six cases experienced minor complications and one case of recurrence was observed. The overall average satisfaction score was 4.1 out of 5, while the satisfaction scores associated with each lesion type were 4.2 for hemangiomas, 3.9 for CMs, 4.2 for VMs, 5.0 for LMs, and 4.0 for AVMs. CONCLUSIONS: It is difficult to completely excise vascular anomalies that involve the vermilion. This study suggests that partial excision focused on correcting the overall contour of the lips is effective and leads to satisfactory results. PMID- 26848440 TI - Cervicofacial Lymphatic Malformations: A Retrospective Review of 40 Cases. AB - BACKGROUND: Lymphatic malformation (LM) is a form of congenital vascular malformation with a low incidence. Although LM has been studied, no consensus has emerged regarding its cause or treatment. METHODS: In this study, we retrospectively evaluated 40 patients who visited our vascular anomalies center for the treatment of cervicofacial LM, which is a common manifestation of LM. The medical records of patients over a period of 12 years were reviewed and analyzed for commonalities regarding the diagnosis and the results of treatment. RESULTS: Suspected cervicofacial LM was confirmed through imaging studies. No difference in incidence was observed according to sex, and 73% of patients first presented with symptoms before the age of two years. The left side and the V2-V3 area were most commonly affected. No significant differences in incidence were observed among the macrocystic, microcystic, and combined types of LM. A total of 28 out of 36 patients received sclerotherapy as the first choice of treatment, regardless of the type of lesion. Complete resolution was achieved in only 25% of patients. CONCLUSIONS: LM is important to confirm the diagnosis early and to choose an appropriate treatment strategy according to the stage of the disease and each individual patient's symptoms. When treatment is delayed or an incorrect treatment is administered, patient discomfort increases as the lesion gradually spreads. Therefore, more so than is the case for most other diseases, a team approach on a case-by-case basis is important for the accurate and appropriate treatment of LM. PMID- 26848442 TI - Closure of Myelomeningocele Defects Using a Limberg Flap or Direct Repair. AB - BACKGROUND: The global prevalence of myelomeningocele has been reported to be 0.8 1 per 1,000 live births. Early closure of the defect is considered to be the standard of care. Various surgical methods have been reported, such as primary skin closure, local skin flaps, musculocutaneous flaps, and skin grafts. The aim of this study was to describe the clinical characteristics of myelomeningocele defects and present the surgical outcomes of recent cases of myelomeningocele at our institution. METHODS: Patients who underwent surgical closure of myelomeningocele at our institution from January 2004 to December 2013 were included in this study. A retrospective chart review of their medical records was performed, and comorbidities, defect size, location, surgical procedures, complications, and the final results were analyzed. RESULTS: A total of 14 patients underwent surgical closure for myelomeningocele defects. Twelve cases were closed with direct skin repair, while two cases required local skin flaps to cover the skin defects. Three cases of infection occurred, requiring incision and either drainage or removal of allogenic materials. One case of partial flap necrosis occurred, requiring secondary revision using a rotational flap and a full-thickness skin graft. Despite these complications, all wounds eventually healed completely. CONCLUSIONS: Most myelomeningocele defects can be managed by direct skin repair alone. In cases of large defects, in which direct repair is not possible, local flaps may be used to cover the defect. Complications such as wound dehiscence and partial flap necrosis occurred in this study; however, all such complications were successfully managed with simple ancillary procedures. PMID- 26848443 TI - Cephalometric Angular Measurements of the Mandible Using Three-Dimensional Computed Tomography Scans in Koreans. AB - BACKGROUND: We conducted this study to analyze the values of the key cephalometric angular measurements of the mandible using 3-dimensional (3D) computed tomography scans. METHODS: In the 106 enrolled patients, a 3D cephalometric analysis was performed to measure the angular variables of the mandible. These values were compared between the two sides and between the two sexes. RESULTS: The frontal measurements revealed that the mandibular body curve angle was larger on the left (Lt) side (right [Rt], 141.24+/-7.54; Lt, 142.68+/ 6.94; P=0.002) and the gonial angle was larger on the right side (Rt, 134.37+/ 8.44; Lt, 131.54+/-7.14; P<0.001). The sagittal measurements showed that the gonial angle was larger on the right side (Rt, 134.37+/-8.44; Lt, 131.54+/-7.14; P>0.05). Further, the transverse measurements revealed that the mandibular body curve angle was larger on the right side (Rt, 140.28+/-7.05; Lt, 137.56+/-6.23; P<0.001). CONCLUSIONS: These results provide an average of the mandibular angular measurements for the Korean population, establishing a standard for determining surgical patient groups and outcome evaluations in the field of mandible contour surgery. PMID- 26848444 TI - Delayed Foreign Body Reaction Caused by Bioabsorbable Plates Used for Maxillofacial Fractures. AB - BACKGROUND: Bioabsorbable plates and screws are commonly used to reduce maxillofacial bones, particularly in pediatric patients because they degrade completely without complications after bone healing. In this study, we encountered eight cases of a delayed foreign body reaction after surgical fixation with bioabsorbable plates and screws. METHODS: A total of 234 patients with a maxillofacial fracture underwent surgical treatment from March 2006 to October 2013, in which rigid fixation was achieved with the Inion CPS (Inion, Tampere, Finland) plating system in 173 patients and Rapidsorb (Synthes, West Chester, PA, USA) in 61 patients. Their mean age was 35.2 years (range, 15-84 years). Most patients were stabilized with two- or three-point fixation at the frontozygomatic suture, infraorbital rim, and anterior wall of the maxilla. RESULTS: Complications occurred in eight (3.4%) of 234 patients, including palpable, fixed masses in six patients and focal swelling in two patients. The period from surgical fixation to the onset of symptoms was 9-23 months. Six patients with a mass underwent secondary surgery for mass removal. The masses contained fibrous tissue with a yellow, grainy, cloudy fluid and remnants of an incompletely degraded bioabsorbable plate and screws. Their histological findings demonstrated a foreign body reaction. CONCLUSIONS: Inadequate degradation of bioabsorbable plates caused a delayed inflammatory foreign body reaction requiring secondary surgery. Therefore, it is prudent to consider the possibility of delayed complications when using bioabsorbable plates and surgeons must conduct longer and closer follow-up observations. PMID- 26848446 TI - Perceptions of Prophylactic Mastectomy in Korea. AB - BACKGROUND: Increasingly, prophylactic mastectomy has been evaluated as a treatment of breast cancer. Hereditary breast cancer now accounts for approximately 5%-10% of all cases of breast cancer, meaning that the widespread implementation of prophylactic mastectomy may significantly reduce the occurrence of breast cancer. However, prophylactic mastectomy is rarely performed in Korea. Therefore, in this study, we assessed Koreans' attitudes toward and awareness of preventive mastectomy. METHODS: This was a prospective study of a cohort of patients attending outpatient clinics and their relatives. Data were collected using self-administered questionnaires assessing sex, age, educational level, knowledge of breast cancer, understanding of prophylactic mastectomy, attitudes toward prophylactic mastectomy, and reasons for choosing prophylactic mastectomy. RESULTS: Sixty-five patients were included. Most patients (36.9%) were between 40 and 49 years of age and 58.4% were college graduates. Only six respondents (9%) understood prophylactic mastectomy, and 17 respondents (27%) stated that they would agree to undergo prophylactic mastectomy if necessary. Reasons given for refusing prophylactic mastectomy included aesthetic concerns (38%), the perception that it would not cure the disease (26%), possible surgical complications (24%), and financial cost (6%). CONCLUSIONS: In this study, most of the respondents showed a poor knowledge of prophylactic mastectomy. Ultimately, it will be necessary to establish medical guidelines for patients with a high risk of breast cancer, with the objective of providing accurate information and proper treatment at hospitals. PMID- 26848445 TI - Sublabial Autologous Ear Cartilage Grafting for Increasing the Nasolabial Angle. AB - BACKGROUND: The loss of nasal tip support is caused by many factors and eventually results in the collapse and eventual dropping of the nasal tip. This reduces the nasolabial (NL) angle and negatively affects respiratory functions and one's appearance. METHODS: The aim of this retrospective study, which was conducted on 52 patients, was to present and popularize a simple and effective method for the reconstruction of a weakened columella by inserting an autologous ear cartilage graft using a sublabial approach. RESULTS: Of all the patients, three patients experienced transplant rejection. The period of follow-up observation was one to five years (mean, 27 months). The results were objectively evaluated by measuring the NL angle in standardized photos before and after the procedure at different time intervals over the follow-up period. We observed a significant increase of the NL angle (mean, 20 degrees ), and found these results to be durable over the long term. Of the 52 patients included in this study observed patients, three were dissatisfied (due to immediate infection and shifting of the strut), 28 were satisfied, and 21 were very satisfied. CONCLUSIONS: The surgical method described here is simple and can be learned quickly. It has very good results with few complications, and is our method of choice for complex and serious cases seen in everyday rhinosurgical practice. PMID- 26848447 TI - Characteristics and Treatment of Cutaneous Melanoma of the Foot. AB - BACKGROUND: In East Asia, the foot is the most common site of cutaneous melanoma. The purpose of this study was to investigate the differences between cutaneous melanoma of the foot and melanomas of other sites. METHODS: We studied 52 patients who underwent surgical treatment for cutaneous melanoma of the foot from September 2000 to January 2015. Through a retrospective review of their medical records, we collected data relating to their sex, age, histopathological subtype, Clark level, tumor thickness, lymph node involvement, stage, and survival rate, and we compared these parameters to those of 61 patients treated for melanoma of other sites. Moreover, we analyzed the surgical procedures, complications, and mortality rates associated with cutaneous melanoma on various parts of the foot. RESULTS: Melanoma of the foot differed from other melanomas only in the histopathological subtype. Other clinical features, including survival rate, did not differ significantly between the two groups heel was the most common site of melanoma of the foot (22 cases, 42.3%). The method of reconstruction varied depending on the region involved. CONCLUSIONS: A comparison of melanoma of the foot to other melanomas showed that melanoma of the foot was associated with a significantly different distribution of histological subtypes. Consistent with previous findings, we found that the acral lentiginous subtype was the most common among melanomas of the foot. Furthermore, in contrast with previous studies, we did not find a worse prognosis or lower survival rate for melanoma of the foot in comparison with other melanomas. PMID- 26848448 TI - Donor-Site Morbidity after Partial Second Toe Pulp Free Flap for Fingertip Reconstruction. AB - BACKGROUND: In this study, we characterize the morbidity at the donor-site of partial second toe pulp free flaps in terms of wound management as well as long term outcomes. METHODS: A single-institutional retrospective review was performed for patients who had undergone partial second toe pulp free flap transfer to the fingertip. Patient charts were reviewed for infection, skin necrosis, wound dehiscence, and hematoma for the donor site. Additionally, a questionnaire survey was given to patients who had a follow-up of longer than 1 year to characterize long-term postoperative pain and appearance. RESULTS: The review identified a total of 246 cases. Early wound complications were significant for wound dehiscence (n=8) and hematoma (n=5) for a wound complication rate of 5.3%. The questionnaire was distributed to 109 patients, and 54 patients completed the survey. Out of these 54 patients, 15 patients continued to have donor-site pain (28%) at a mean follow-up period of 32.4 months. However, the pain intensity was relatively low in the range between 2 to 5, on a 0-10 scale. None of these patients felt this donor-site pain interfered significantly with daily activity, nor did any patient require pain medications of any type. Donor-site appearance was satisfactory to most patients. CONCLUSIONS: The partial second toe pulp flap was associated with low rates of wound complications and favorable long-term outcomes. Given the functional and aesthetic gain in the recipient finger, donor site morbidities appear acceptable in this patient population. This study can be helpful in counseling patients regarding donor-site morbidity during the informed consent process. PMID- 26848449 TI - Analysis of 344 Hand Injuries in a Pediatric Population. AB - BACKGROUND: The purpose of this study was to identify comprehensive hand injury patterns in different pediatric age groups and to assess their risk factors. METHODS: This retrospective study was conducted among patients younger than 16 year-old who presented to the emergency room of a general hospital located in Gyeonggi-do, Republic of Korea, and were treated for an injury of the finger or hand from January 2010 to December 2014. The authors analyzed the medical records of 344 patients. Age was categorized according to five groups. RESULTS: A total of 391 injury sites of 344 patients were evaluated for this study. Overall and in each group, male patients were in the majority. With regard to dominant or non dominant hand involvement, there were no significant differences. Door-related injuries were the most common cause in the age groups of 0 to 3, 4 to 6, and 7 to 9 years. Sport/recreational activities or physical conflict injuries were the most common cause in those aged 10 to 12 and 13 to 15. Amputation and crushing injury was the most common type in those aged 0 to 3 and 4 to 6 years. However, in those aged 10 to 12 and 13 to 15, deep laceration and closed fracture was the most common type. With increasing age, closed injuries tended to increase more sharply than open injuries, extensor tendon rupture more than flexor injuries, and the level of injury moved proximally. CONCLUSIONS: This study provides a comprehensive overview of the epidemiology of hand injuries in the pediatric population. PMID- 26848450 TI - Lateral Nasal Artery Perforator Flaps: Anatomic Study and Clinical Applications. AB - BACKGROUND: Previous studies have investigated facial artery perforators, but have reported inconsistent results regarding lateral nasal artery (LNA) perforators. Although several authors have described the use of LNA perforators for ala nasi and nasal sidewall reconstruction, the literature contains little information regarding the cadaveric dissection of LNA perforators, and most previously published studies have focused on facial artery perforators. METHODS: Sixteen hemifaces from eight fresh cadavers were dissected to study the LNA perforators. After the dissection was performed, the total length and diameter of the LNA and its perforators were measured. The quantity and the distribution of the LNA perforators supplying the overlying skin were then assessed. LNA perforator flaps were used for reconstruction in 10 nasal and perinasal defects. RESULTS: The mean total lengths of the LNA and its perforators were 49.37 mm and 16.06 mm, respectively. The mean diameters of the LNA and its perforators were 2.08 mm and 0.91 mm, respectively. Based on our findings, we mapped the face to indicate zones with a higher probability of finding perforators. No infection, hematoma, or complete flap necrosis were observed after the procedures. CONCLUSIONS: Nasal reconstruction is a challenging procedure, and LNA propeller/V Y perforator flaps are an excellent reconstructive option in certain cases. Based on our cadaveric study, we were able to identify an area in the upper third of the nasolabial groove with a high density of perforators. PMID- 26848451 TI - A Wrapping Method for Inserting Titanium Micro-Mesh Implants in the Reconstruction of Blowout Fractures. AB - Titanium micro-mesh implants are widely used in orbital wall reconstructions because they have several advantageous characteristics. However, the rough and irregular marginal spurs of the cut edges of the titanium mesh sheet impede the efficacious and minimally traumatic insertion of the implant, because these spurs may catch or hook the orbital soft tissue, skin, or conjunctiva during the insertion procedure. In order to prevent this problem, we developed an easy method of inserting a titanium micro-mesh, in which it is wrapped with the aseptic transparent plastic film that is used to pack surgical instruments or is attached to one side of the inner suture package. Fifty-four patients underwent orbital wall reconstruction using a transconjunctival or transcutaneous approach. The wrapped implant was easily inserted without catching or injuring the orbital soft tissue, skin, or conjunctiva. In most cases, the implant was inserted in one attempt. Postoperative computed tomographic scans showed excellent placement of the titanium micro-mesh and adequate anatomic reconstruction of the orbital walls. This wrapping insertion method may be useful for making the insertion of titanium micro-mesh implants in the reconstruction of orbital wall fractures easier and less traumatic. PMID- 26848452 TI - Visible Perforating Lateral Osteotomy: Internal Perforating Technique with Wide Periosteal Dissection. AB - There are two general categories of lateral osteotomy techniques-the external perforating method and the internal continuous method. Regardless of which technique is used, procedural effectiveness is hampered by limited visualization in the surgical field. Considering this point, we devised a new technique that involves using a wide subperiosteal dissection and internal perforation under direct visualization. Using an intranasal approach, whereby the visibility of the intended fracture line was maintained, enabled a greater degree of control, and in turn, results that were more precise, and thus predictable and reproducible. Traditionally, it has been taken as dogma that the periosteum must be preserved, considering the potential for dead space and bony instability; however, under sufficient visualization of the surgical field with an internal perforating method, complete osteotomy with fully preserved intranasal mucosa could be conducted exactly as intended. This intact mucosal lining compensates for the elevated periosteum. Compressive dressing and drainage through a Silastic angio needle catheter enabled the elimination of dead space. Therefore, precise, reproducible, and predictable osteotomy minimizing the potential for associated complications such as ecchymosis, that is, bruising owing to hemorrhage, could be performed. In this article, we introduce a novel technique for lateral osteotomy with improved visualization. PMID- 26848453 TI - The Role of Nanofat Grafting in Vulvar Lichen Sclerosus: A Preliminary Report. PMID- 26848454 TI - Congenital Insensitivity to Pain and Anhidrosis. PMID- 26848455 TI - Emergency Transplantation of Free Flap between Separated Thoraco-Omphalopagus Conjoined Twins. PMID- 26848456 TI - Transient Exotropia after Open Reduction of a Naso-Ethmoidal-Orbital Fracture. PMID- 26848457 TI - Excision of a Lower Eyelid Inflammatory Pseudotumor Combined with Lower Blepharoplasty. PMID- 26848458 TI - Huge Ancient Hematoma in the Calf. PMID- 26848459 TI - Salivary Duct Carcinoma of the Deep Lobe of the Parotid Gland: A Rare Clinical Finding. PMID- 26848460 TI - Low-Grade Fibromyxoid Sarcoma of the Malar Area. PMID- 26848461 TI - Squamous Cell Carcinoma Arising from an Epidermal Inclusion Cyst. PMID- 26848462 TI - Extra-Abdominal Desmoid Tumor in the Donor Site of an Extended Latissimus Dorsi Flap. PMID- 26848463 TI - Treatment of Tuberculous Empyema by Intrathoracic Transposition of a Latissimus Dorsi Muscle Flap. PMID- 26848464 TI - Non-Invasive Imaging of Preoperative Mapping of Superficial Veins in Free Flap Breast Reconstruction. PMID- 26848465 TI - A Simple Modified Flip-Flop Flap for the Reconstruction of Antihelix and Triangular Fossa Defects. PMID- 26848466 TI - A Rare Case of Massive Localized Lymphedema in a Morbidly Obese Patient. PMID- 26848467 TI - Erratum: Scar Revision Surgery: The Patient's Perspective. AB - [This corrects the article on p. 729 in vol. 42, PMID: 26618120.]. PMID- 26848468 TI - Operative Treatment of Isolated Bicondylar Hoffa Fracture With a Modified Swashbuckler Approach. AB - INTRODUCTION: An isolated coronal fracture of either or both femoral condyles is a rare entity and is usually associated with high-energy injury trauma. Such fractures should be meticulously fixed for a good functional outcome as they involve the articular surface of a weight bearing joint. A modified swashbuckler approach provides adequate exposure for appropriate reduction and fixation of such fractures. CASE PRESENTATION: A 32-year-old male sustained a bicondylar Hoffa fracture of the right femur which was treated by open reduction and internal fixation using a modified swashbuckler approach. At two years of follow up, the patient had excellent radiological and functional outcome. CONCLUSIONS: In our study, we treated this rare fracture successfully using a modified swashbuckler approach and found it to be a good approach for such fractures as compared to the conventional approach. PMID- 26848469 TI - Functional Independence Measure in Iran: A Confirmatory Factor Analysis and Evaluation of Ceiling and Floor Effects in Traumatic Brain Injury Patients. AB - BACKGROUND: The functional independence measure (FIM) is one of the most important assessment instruments for motor and cognitive dependence in rehabilitation medicine; however, there is little data about its confirmatory factor analysis (CFA) and ceiling/floor effects from other countries and also in Iranian patients. OBJECTIVES: The aim of this study was to evaluate a two-factor model (motor and cognitive independence as latent variables) and ceiling/floor effects for FIM in Iranian patients with traumatic brain injuries (TBI). PATIENTS AND METHODS: In this cross-sectional study, 185 subacute TBI patients were selected from emergency and neurosurgery departments of Poursina Hospital (the largest trauma hospital in northern Iran, Rasht) using the consecutive sampling method and were assessed for functional independence. RESULTS: The results of this study showed that the floor effect was not observed; however, ceiling effects were observed for the FIM total score and its subscales. The confirmatory factor analysis showed that the chi-square/df ratio was 2.8 for the two-factor structure and the fit indices for this structural model including root mean square error of approximation (RMSEA) = 0.099, normed fit index (NFI) = 0.96, tucker lewis index (TLI) = 0.97, comparative fit index (CFI) = 0.97 were close to standard indices. CONCLUSIONS: Although ceiling effects should be considered for rehabilitation targets, the two-factor model of FIM (motor and cognitive independence) has an eligible fitness for Iranian patients with TBI. PMID- 26848470 TI - Open Repair Versus Thoracic Endovascular Aortic Repair in Multiple-Injured Patients: Observations From a Level-1 Trauma Center. AB - BACKGROUND: Blunt trauma of the thoracic aorta is a rare but potentially life threatening entity. Intimal tears are a domain of non-operative management, whereas all other types of lesions should be repaired urgently. There is now a clear trend favoring minimally invasive stent grafting over open surgical repair. OBJECTIVES: The aim of the present study was to retrospectively evaluate the mortality and morbidity with either treatment option. Therefore, a retrospective observational study was performed to compare two different treatment methods at two different time periods at one trauma center. PATIENTS AND METHODS: Between 1977 and 2012, all severely injured patients referred to our level 1 trauma center were screened for blunt aortic injuries. We compared baseline characteristics, 30-day and overall mortality, morbidity, duration of intensive care treatment, procedure time, and transfusion of packed red blood between patients who underwent open surgical or stent repair. RESULTS: During the observation period, 45 blunt aortic injuries were recorded. The average Injury Severity Score (ISS) was 41.8 (range 29 - 68). Twenty-five patients underwent Open Repair (OR), and another 20 patients were scheduled to emergency stent grafting. The 30-day mortality in the surgical and stent groups were 5/25 (20%) and 2/20 (10%), respectively. The average time for open surgery was 151 minutes; the mean time for stent grafting was 67 minutes (P = 0.001). Postoperative stay on the intensive care unit was between one and 59 days (median 10) in group one and between four and 50 days in group two (median 26)(P = 0.03). Patients undergoing OR required transfusion of 6.0 units of packed red cells in median; patients undergoing stent grafting required a median of 2.0 units of packed red cells (P < 0.001). In the stent grafting group, 30-day mortality was 10% (2/20). CONCLUSIONS: Due to more sophisticated diagnostic tools and surgical approaches, mortality and morbidity of blunt aortic injuries were significantly reduced over the years compared to thoracic endovascular aortic repair and OR over two different time periods. PMID- 26848471 TI - Rib Fracture Fixation Restores Inspiratory Volume and Peak Flow in a Full Thorax Human Cadaveric Breathing Model. AB - BACKGROUND: Multiple rib fractures cause significant pain and potential for chest wall instability. Despite an emerging trend of surgical management of flail chest injuries, there are no studies examining the effect of rib fracture fixation on respiratory function. OBJECTIVES: Using a novel full thorax human cadaveric breathing model, we sought to explore the effect of flail chest injury and subsequent rib fracture fixation on respiratory outcomes. PATIENTS AND METHODS: We used five fresh human cadavers to generate negative breathing models in the left thorax to mimic physiologic respiration. Inspiratory volumes and peak flows were measured using a flow meter for all three chest wall states: intact chest, left-sided flail chest (segmental fractures of ribs 3 - 7), and post-fracture open reduction and internal fixation (ORIF) of the chest wall with a pre contoured rib specific plate fixation system. RESULTS: A wide variation in the mean inspiratory volumes and peak flows were measured between specimens; however, the effect of a flail chest wall and the subsequent internal fixation of the unstable rib fractures was consistent across all samples. Compared to the intact chest wall, the inspiratory volume decreased by 40 +/- 19% in the flail chest model (P = 0.04). Open reduction and internal fixation of the flail chest returned the inspiratory volume to 130 +/- 71% of the intact chest volumes (P = 0.68). A similar 35 +/- 19% decrease in peak flows was seen in the flail chest (P = 0.007) and this returned to 125 +/- 71% of the intact chest following ORIF (P = 0.62). CONCLUSIONS: Negative pressure inspiration is significantly impaired by an unstable chest wall. Restoring mechanical stability of the fractured ribs improves respiratory outcomes similar to baseline values. PMID- 26848472 TI - Prevalence of Posttraumatic Stress Disorder and Related Factors Among Patients Discharged From Critical Care Units in Kashan, Iran. AB - BACKGROUND: Posttraumatic Stress Disorder (PTSD) is a severe anxiety disorder occurred due to past adverse experiences. Several researches have demonstrated that PTSD is quite common among patients discharged from critical care unit. OBJECTIVES: This study aimed to investigate the prevalence of PTSD and its related factors among patients discharged from critical care units in Kashan, Iran, during 2014. PATIENTS AND METHODS: A descriptive prospective study was performed on 332 patients admitted to critical care units of Kashan Shahid Beheshti Hospital using a convenience sampling method. Data were collected in wards during hospitalization and one month after their discharge from hospital using questionnaires on demographic, medical information and PTSD Checklist (PCL). The PCL scores of 45 or more were considered as PTSD. Data were analyzed using chi-square, t-test, Mann-Whitney U and logistic regression. RESULTS: From a total of 332 patients, 160 cases (48.2%) had PTSD and the mean total PCL score in participants was 44.24 +/- 19.89. There was a significant difference between the total score of PTSD and its domains in patients with and without PTSD. the univariate analysis showed a significant association between PTSD and increasing age, increased length of hospital stay, more children, having additional comorbidities, unemployed, use of mechanical ventilation (P < 0.001), drug abuse (P = 0.003) and single patients (P = 0.028). However, there was no significant association between PTSD and gender, type of the critical care unit, level of education and admission due to trauma. However, in multivariate analysis using logistic regression, factors associated with PTSD were older age of the participants, use of mechanical ventilation having additional comorbidities, unemployed (P<0.001) and being single (P=0.04). CONCLUSIONS: Prevalence of PTSD is high among patients discharged from ICUs and some medical individual factors such as elderly, unemployed, being single, using mechanical ventilation and pre existing diseases are risk factors. Therefore, it is recommended to perform appropriative educational plan for these patients to reduce the risk of PTSD. PMID- 26848474 TI - Management and Prognostic Factors for Delayed Reconstruction of Neglected Posterior Shoulder Fracture-Dislocation. AB - INTRODUCTION: Posterior fracture-dislocations of the shoulder are rare conditions. Misdiagnosis can occur in 50% - 80% of the patients. Due to the size of the lesion, stability of the joint could not be achieved with transfer of subscapular tendon or tuberosity. CASE PRESENTATION: A 54-year-old male patient was referred to our hospital with a neglected posterior shoulder fracture dislocation. Functional results of the patient, and technical informations were explained in this case report. The reverse Hill-Sachs lesion involved 40% of the articular surface. Depressed and malunited fragment was elevated, and fixated to the humeral head. CONCLUSIONS: Glenohumeral joint reduction with reconstruction of the humeral head seems to be possible even in a neglected locked posterior shoulder fracture-dislocation. If the depressed osteochondral fragment is still spheric, signs of the avascular necrosis are absent on CT, and malunion of the fragment has occurred, it is quite possible to reconstruct the head. Although results of the case are good, it is worthwhile to follow these patients for long term complications. PMID- 26848473 TI - Effectiveness of Five-Level Emergency Severity Index Triage System Compared With Three-Level Spot Check: An Iranian Experience. AB - BACKGROUND: Triage for patients' prioritization in the emergency department is a suitable solution to decrease overcrowding. Different methods are used for prioritization that needs effectiveness evaluation. OBJECTIVES: The aim of this study was to assess the effectiveness of the emergency severity index (ESI) 5 level triage system in contrast with spot check triage. PATIENTS AND METHODS: Data for this quasi-experimental study were extracted using a form to review 770 records of patients referred to emergency department of Imam Khomeini hospital (in Sari, north of Iran) during two separated periods each for four months; the first from 20th March to 19th July 2010 and the other from 21 March to 20 July 2011. The method used in the first time was spot check triage and the second one ESI triage. Data were processed with descriptive statistics and analyzed using independent samples t-test (CI = 95%). RESULTS: Increase from 6.46 to 8.92 minutes in the average time from patient arrival to being visited by a physician (P < 0.001) and increase in average time from physician visit to receive the first nursing care from 7.68 to 15.89 minutes were significant (P < 0.001). The average waiting time for laboratory services was significantly decreased from 112.3 to 84.1 (P = 0.033). Increase in the average waiting time for radiology, decrease in average waiting time for sonography, average length of stay in the emergency department, and number of patients per emergency bed were not significant. CONCLUSIONS: Between the two systems of triage, ESI was more effective than the spot check and in the spatial and temporal domain of research, was a successful method in improving some indicators of emergency and improving the performance indices. Hospital managers by implementation of ESI system can take a step toward new health policies and improve the processes as key tools of continuous quality improvement system. PMID- 26848475 TI - Operative Treatment of an Atypical Segmental Bipolar Fracture of the Clavicle. AB - INTRODUCTION: Clavicle fractures are very common, accounting for approximately 4% of all adult fractures. Segmental bipolar fractures involving the lateral and the medial ends of the clavicle are extremely rare, with only isolated cases reported in the literature. The injury mechanism is often unclear and the management of these fractures remains controversial. CASE PRESENTATION: Here is to report a case of a segmental bipolar fracture of the clavicle with a lateral fracture and a displaced medial fracture without dislocation of the sternoclavicular joint following a low energy fall to the outstretched hand, and discuss its management. CONCLUSIONS: Stability of the clavicle is crucial for shoulder function and care should be taken not to miss or underestimate segmental bipolar fractures even with a low energy mechanism. Authors believe that operative treatment should be taken into consideration for displaced fractures. PMID- 26848477 TI - Evaluation of the Safe Ischemic Time of Clamping During Intermittent Pringles Maneuver in Rabbits. AB - BACKGROUND: The liver is the most commonly injured organ in blunt abdominal trauma. Although major hepatic bleeding may be partially controlled with portal triade clamping (the Pringle's maneuver), continuous prolonged clamping results in liver ischemia. OBJECTIVES: The purpose of this study was to determine the safe time of Pringle maneuver based on pathologic changes of liver in rabbit models. MATERIALS AND METHODS: In an experimental study, 20 New-Zealand white rabbits were selected. In laparotomy, a blunt dissector was passed through the foramen of Winslow and the hepato-duodenal ligament encircled with an umbilical tape. En masse Pringle maneuver was performed using atraumatic flexible clamps. Rabbits were divided into four groups based on Pringle maneuver time (30 minutes, 45 minutes, 60 minutes, and 75 minutes). A hepatic biopsy was performed at the beginning of operation. The degree of tissue injury was evaluated using blood markers. RESULTS: There were five rabbits in each group. At the end of 60 minutes ischemia, only minor alterations were observed in pathological specimens. At the end of 75 minutes, hepatocyte damage and necrosis were observed. The serum levels of alanine aminotransferase (Group A: P = 0.02; Group B: P = 0.01; Group C: P = 0.0002; Group D: P = 0.01) and Aspartate aminotransferase (Group A: P = 0.03; Group B: P = 0.002; Group C: P = 0.0004; Group D: P = 0.0003) were significantly increased post-operatively. The maximum level was in the first day after operation. CONCLUSIONS: Continuous portal triade clamping (the Pringle maneuver) during liver ischemia (30 and 45 minutes) in rabbits resulted in no ischemic change. Increasing time of clamping to 30 minutes was safe in intermittent Pringle maneuver. PMID- 26848476 TI - New Prognostic Biomarkers in Patients With Traumatic Brain Injury. AB - CONTEXT: Traumatic brain injury (TBI) is a leading cause of death, disability, and resource consumption per year. There are two kinds of brain injury in TBI, primary and secondary injuries. Primary injury refers to the initial physical forces applied to the brain at the moment of impact. Secondary injury occurs over a period of hours or days following the initial trauma and results from the activation of different pathways such as inflammation, coagulation, oxidation, and apoptosis. EVIDENCE ACQUISITION: This review focuses on new prognostic biomarkers of mortality in TBI patients related to inflammation, coagulation, oxidation, and apoptosis. RESULTS: Recently circulating levels of substance P (SP), soluble CD40 ligand (sCD40L), tissue inhibitor of matrix metalloproteinases (TIMP)-1, malondialdehyde (MDA), and cytokeratin (CK)-18 fragmented have been found to be associated with mortality in TBI patients. Substance P is a neuropeptide of the tachykinin family, mainly synthesized in the central and peripheral nervous system, with proinflammatory effects when binding to their neurokinin-1 receptor (NK1R). Soluble CD40 ligand, a member of the tumor necrosis factor (TNF) family that is released into circulation from activated platelets, exhibit proinflamatory, and procoagulant properties on binding to their cell surface receptor CD40. Matrix metalloproteinases (MMPs) are a family of zinc containing endoproteinases involved neuroinflammation and TIMP-1 is the inhibitor of some of them. Malondialdehyde is an end-product formed during lipid peroxidation due to degradation of cellular membrane phospholipids, that is released into extracellular space and finally into the blood. Cytokeratin -18 is cleaved by the action of caspases during apoptosis, and CK-18 fragmented is released into the blood. CONCLUSIONS: Circulating levels of some biomarkers, such as SP, sCD40L, TIMP-1, MDA, and CK-18 fragmented, related to inflammation, coagulation, oxidation, and apoptosis have been recently associated with mortality in patients with TBI. These biomarkers could help in the prognostic classification of the patients and open new research lines in the treatment of patients with TBI. PMID- 26848479 TI - Autologous pubovaginal slings: back to the future or a lost art? AB - Stress urinary incontinence (SUI) is an under-diagnosed problem affecting up to 50% of women worldwide. SUI is a source of psychological distress to the individual and also imposes a financial burden to the individual and the health care system. The role of surgery in the treatment in SUI has evolved steadily in the last two decades. The synthetic mid-urethral sling and its different insertion methods have gained widespread popularity and are now the most frequently used surgical interventions for women with SUI in Europe. As the use of synthetic slings becomes more widespread, an increasing number of complications are being reported. With the recent concerns surrounding the use of synthetic transvaginal meshes in organ prolapse surgery, synthetic slings have been put under further scrutiny. It is imperative for health care providers to be aware of the current issues associated with synthetic slings and the alternative surgical options available. Traditional autologous pubovaginal slings (PVS) have re-emerged as a viable alternative to synthetic slings in light of the issues with synthetic slings. The re-adoption of autologous PVS has however, been slow due to the technical difficulty of the surgery and perceived higher morbidity rates. In this article, we will discuss the various aspects of autologous PVS and its indications as an alternative to synthetic slings. We will also touch on the current evidence and controversies for synthetic mesh slings. PMID- 26848478 TI - Intravenous Paracetamol Versus Patient-Controlled Analgesia With Morphine for the Pain Management Following Diagnostic Knee Arthroscopy in Trauma Patients: A Randomized Clinical Trial. AB - BACKGROUND: Most patients undergoing outpatient surgeries have the unpleasant experience of high level pain after surgery. Compared with open surgeries, arthroscopic procedures are less painful; however, inadequate pain management could be associated with significant concerns. Opioids alone or in combination with local anesthetics are frequently used for diminishing postoperative pain using intravenous or epidural infusion pumps. Despite morphine various disadvantages, it is commonly used for controlling pain after surgery. OBJECTIVES: The aim of this study was to compare intravenous paracetamol and patient-controlled analgesia (PCA) with morphine for the pain management following diagnostic knee arthroscopy in trauma patients. PATIENTS AND METHODS: Sixty trauma patients who were scheduled to undergo knee arthroscopy were randomly divided into two groups. Patients immediately received intravenous infusion of 1 g paracetamol within 15 minutes after surgery and every 6 hours to 24 hours in the paracetamol group. The patient-controlled analgesia group received morphine through PCA infusion pump at 2 mL/h base rate and 1mL bolus every 15 minutes. Pain level, nausea and vomiting, and sedation were measured and recorded during entering the recovery, 15 and 30 minutes after entering the recovery, 2, 6, and 24 hours after starting morphine pump infusion in the morphine and paracetamol in the paracetamol groups. RESULTS: There was no significant difference regarding the pain level at different times after entering the recovery between the two groups. No one from the paracetamol group developed drug complications. However, 22.3% in the PCA morphine suffered from postoperative nausea; there was a statistically significant difference regarding the sedation level, nausea, and vomiting at various times between the two groups. CONCLUSIONS: Intravenous administration of paracetamol immediately after knee arthroscopy improved postoperative pain, decreased analgesic administration, maintained stable hemodynamic parameters, had no complications related to opiates, no nausea and vomiting, and increased patient satisfaction and comfort in comparison to PCA with morphine. PMID- 26848480 TI - Led Astray by Hemoglobin A1c: A Case of Misdiagnosis of Diabetes by Falsely Elevated Hemoglobin A1c. AB - Hemoglobin A1c (A1c) is used frequently to diagnose and treat diabetes mellitus. Therefore, it is important be aware of factors that may interfere with the accuracy of A1c measurements. This is a case of a rare hemoglobin variant that falsely elevated a nondiabetic patient's A1c level and led to a misdiagnosis of diabetes. A 67-year-old male presented to endocrine clinic for further management after he was diagnosed with diabetes based on an elevated A1c of 10.7%, which is approximately equivalent to an average blood glucose of 260 mg/dL. Multiple repeat A1c levels remained >10%, but his home fasting and random glucose monitoring ranged from 92 to 130 mg/dL. Hemoglobin electrophoresis and subsequent genetic analysis diagnosed the patient with hemoglobin Wayne, a rare hemoglobin variant. This variant falsely elevates A1c levels when A1c is measured using cation-exchange high-performance liquid chromatography. When the boronate affinity method was applied instead, the patient's A1c level was actually 4.7%. Though hemoglobin Wayne is clinically silent, this patient was erroneously diagnosed with diabetes and started on an antiglycemic medication. Due to this misdiagnosis, the patient was at risk of escalation in his "diabetes management" and hypoglycemia. Therefore, it is important that providers are aware of factors that may result in hemoglobin A1c inaccuracy including hemoglobin variants. PMID- 26848481 TI - Concussion Incidence in Professional Football: Position-Specific Analysis With Use of a Novel Metric. AB - BACKGROUND: In the United States alone, millions of athletes participate in sports with potential for head injury each year. Although poorly understood, possible long-term neurological consequences of repetitive sports-related concussions have received increased recognition and attention in recent years. A better understanding of the risk factors for concussion remains a public health priority. Despite the attention focused on mild traumatic brain injury (mTBI) in football, gaps remain in the understanding of the optimal methodology to determine concussion incidence and position-specific risk factors. PURPOSE: To calculate the rates of concussion in professional football players using established and novel metrics on a group and position-specific basis. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Athletes from the 2012 2013 and 2013-2014 National Football League (NFL) seasons were included in this analysis of publicly available data. Concussion incidence rates were analyzed using established (athlete exposure [AE], game position [GP]) and novel (position play [PP]) metrics cumulatively, by game unit and position type (offensive skill players and linemen, defensive skill players and linemen), and by position. RESULTS: In 480 games, there were 292 concussions, resulting in 0.61 concussions per game (95% CI, 0.54-0.68), 6.61 concussions per 1000 AEs (95% CI, 5.85-7.37), 1.38 concussions per 100 GPs (95% CI, 1.22-1.54), and 0.17 concussions per 1000 PPs (95% CI, 0.15-0.19). Depending on the method of calculation, the relative order of at-risk positions changed. In addition, using the PP metric, offensive skill players had a significantly greater rate of concussion than offensive linemen, defensive skill players, and defensive linemen (P < .05). CONCLUSION: For this study period, concussion incidence by position and unit varied depending on which metric was used. Compared with AE and GP, the PP metric found that the relative risk of concussion for offensive skill players was significantly greater than other position types. The strengths and limitations of various concussion incidence metrics need further evaluation. CLINICAL RELEVANCE: A better understanding of the relative risks of the different positions/units is needed to help athletes, team personnel, and medical staff make optimal player safety decisions and enhance rules and equipment. PMID- 26848482 TI - Risk Stratification for Ulnar Collateral Ligament Injury in Major League Baseball Players: A Retrospective Study From 2007 to 2014. AB - BACKGROUND: Ulnar collateral ligament (UCL) injury has become increasingly common in Major League Baseball (MLB) players in recent years. HYPOTHESIS: There is a significant difference in preinjury fastball velocity between MLB pitchers with tears and matched controls without UCL injury. Pitchers with injuries are throwing harder and getting injured earlier in their MLB careers. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: From 2007 to 2014, a total of 170 documented UCL injuries (156 pitchers, 14 position players) occurred in MLB. Inclusion criteria for this study consisted of any player who tore his UCL in MLB during this time frame. There were 130 regular-season tears (April-September). From this group, 118 players who pitched more than 100 innings prior to tear were matched to subjects with no tear and were compared using a logistic regression analysis. A subgroup of "early tear" players who threw less than 100 career innings (n = 37) was also identified and compared with the larger tear group using a logistic regression analysis. RESULTS: Of the 130 tears that occurred during the regular season, a significantly larger number (62%) occurred in the first 3 months (P = .011). The rate of UCL tears per MLB player (P = .001) was statistically significant. In the group of 118 matched tears, the mean fastball velocity was greater in the tear group (91.7 mph) compared with the control group (91.0 mph; P = .014). Furthermore, relief pitchers made up a greater percentage of the early tear group (<100 innings) compared with the later tear group (P = .011). Sixteen of the 170 UCL tears (9.4%) were recurrent tears, with 5 of 16 experiencing both tear and retear within the past 4 years. CONCLUSION: There is a statistically significant difference in the mean fastball velocity of pitchers who injure their UCL. Small increases in pitcher fastball velocity are a main contribution to the increased rate of tear in MLB. In addition, there has been an increased incidence of injury in the first 3 months of the season. Finally, early tears are more likely to occur in relief pitchers than starters. PMID- 26848483 TI - Disseminated Leishmaniasis by Leishmania viannia Subgenus: A Series of 18 Cases in Southeastern Brazil. AB - Background. Disseminated leishmaniasis (DL) is an emerging clinical form of American tegumentary leishmaniasis (ATL) that occurs mainly in Northeastern Brazil. This study describes 18 cases where DL has not yet been reported. Methods. Disseminated leishmaniasis cases were extracted from ATL recorded cases between 1987 and March 2015. Disseminated leishmaniasis identification was based on >=10 mixed-type lesions, located in >=2 body parts. Results. Eighteen (5.4%) patients were identified as DL. Polymerase chain reaction followed by enzymatic digestion confirmed Leishmania viannia subgenus in 17 patients; amastigotes forms were identified in another one. Conclusions. Considering that DL diagnosis and management is challenging, clinicians must be aware of this emerging clinical form of the disease. PMID- 26848484 TI - What Are the Recommended Timing and Screening Modalities in Women at Higher Risk for Developing Breast Cancer? A Clin-IQ. AB - Early detection of breast cancer is desirable to prevent progression to advanced disease. This subject has been one of significant study and debate for women at normal risk, and recommendations continue to evolve. However, with regard to women at high risk, the recommendations from various health care professional organizations, including the recent recommendations from the United States Preventative Services Task Force, are different and also inconsistent concerning when to begin screening and which modalities should be used. We review several randomized controlled trials and consensus opinions regarding when to begin screening for breast cancer and how to best screen women at high risk. Specifically, we address women with known personal history of breast cancer, prior mantle radiation, or specific family history (including genetic family history) of breast cancer. The purpose of this inquiry is to present current evidence and suggest a clinical pathway regarding the screening of women at high risk for breast cancer. PMID- 26848485 TI - Converging mediators from immune and trophic pathways to identify Parkinson disease dementia. AB - OBJECTIVE: To identify a panel of peripheral inflammatory/immune mediators that could discriminate Parkinson disease with dementia (PDD) from Parkinson disease (PD) without dementia. METHODS: Plasma samples from 52 patients with PD and 22 patients with PDD were prepared from freshly collected blood following an institutional review board-approved protocol. A total of 160 proteins were measured using a multiplex antibody array. Plasma alpha-synuclein levels were analyzed by an electrochemiluminescence immunoassay. The main objective of the statistical analyses was to identify PDD discriminants using the plasma protein profile alone or in combination with age. RESULTS: The PD and PDD groups differed significantly in cognitive measurements (Mini-Mental State Examination, Auditory Verbal Learning Test-A7, and Clinical Dementia Rating) and age. The age-adjusted levels of thymus and activation-regulated chemokine (TARC) and platelet-derived growth factor (PDGF)-AA were significantly different between disease groups. The levels of plasma alpha-synuclein significantly correlated with 26 proteins; among them, PDGF-BB, TARC, PDGF-AA, and epidermal growth factor were the highest. Linear discriminant analysis with leave-one-out cross-validation identified a 14 protein panel with age as discriminants of PDD (96% sensitivity, 89% specificity, area under the curve = 0.9615). CONCLUSIONS: We showed that multiple proteins that are mediators of growth/trophic and immune response-related pathways had discriminatory power for identifying PDD in patients with PD. Validation of this discovery-based study in longitudinal population-based studies is warranted. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a 14 protein panel plasma assay combined with age has a sensitivity of 96% and a specificity of 89% for PDD. PMID- 26848486 TI - Therapy with natalizumab is associated with high JCV seroconversion and rising JCV index values. AB - OBJECTIVE: The aim of the study was to analyze John Cunningham virus (JCV) serology in natalizumab-treated patients over time and assess whether they are influenced by natalizumab treatment. METHODS: German (n = 1,921; 525 longitudinally) and French (n = 1,259; 711 longitudinally) patients were assessed for JCV serology alongside their therapy with natalizumab. RESULTS: JCV serostatus changed in 69 of 525 longitudinally followed German patients (13.1%) over 14.8 months. Seroconversion according to serostatus was seen in 43 of 339 initially JCV- German patients (12.7% in 14.8 months; 10.3% per year) and 41 of 243 initially JCV- French patients (16.9% in 24 months; 8.5% per year). JCV index values could be reproduced (R (2) = 0.89) with the caveat of 8 of 50 samples (16%) being set into different risk categories between 2 assessments. Index values of JCV+ patients rose over time (p = 0.009) but not because of aging. Treatment with natalizumab was associated with a 15.9% increase of value in JCV+ patients in 14.8 months (12.9% per year). CONCLUSIONS: JCV seroconversion and index values may be influenced by treatment with natalizumab. It is therefore important to monitor patients' JCV serology but also to incorporate additional risk factors into the progressive multifocal leukoencephalopathy risk stratification. PMID- 26848487 TI - Patients with MS under daclizumab therapy mount normal immune responses to influenza vaccination. AB - OBJECTIVE: The purpose of this study was to assess the potential immunosuppressive role of daclizumab, a humanized monoclonal antibody against the alpha chain of the interleukin 2 receptor, in vivo, by comparing immune responses to the 2013 seasonal influenza vaccination between patients with multiple sclerosis (MS) on long-term daclizumab therapy and controls. METHODS: Previously defined subpopulations of adaptive immune cells known to correlate with the immune response to the influenza vaccination were evaluated by 12-color flow cytometry in 23 daclizumab-treated patients with MS and 14 MS or healthy controls before (D0) and 1 day (D1) and 7 days (D7) after administration of the 2013 Afluria vaccine. Neutralizing antibody titers and CD4(+), CD8(+) T cell, B cell, and natural killer cell proliferation to 3 strains of virus contained in the Afluria vaccine were assessed at D0, D7, and 180 days postvaccination. RESULTS: Daclizumab-treated patients and controls demonstrated comparable, statistically significant expansions of previously defined subpopulations of activated CD8(+) T cells and B cells that characterize the development of effective immune responses to the influenza vaccine, while proliferation of T cells to influenza and control antigens was diminished in the daclizumab cohort. All participants fulfilled FDA criteria for seroconversion or seroprotection in antibody assays. CONCLUSION: Despite the mild immunosuppressive effects of daclizumab in vivo demonstrated by an increased incidence of infectious complications in clinical trials, patients with MS under daclizumab therapy mount normal antibody responses to influenza vaccinations. PMID- 26848488 TI - Rising JCV-Ab index during natalizumab therapy for MS: Inauspicious for a highly efficacious drug. PMID- 26848490 TI - Module Extraction for Efficient Object Queries over Ontologies with Large ABoxes. AB - The extraction of logically-independent fragments out of an ontology ABox can be useful for solving the tractability problem of querying ontologies with large ABoxes. In this paper, we propose a formal definition of an ABox module, such that it guarantees complete preservation of facts about a given set of individuals, and thus can be reasoned independently w.r.t. the ontology TBox. With ABox modules of this type, isolated or distributed (parallel) ABox reasoning becomes feasible, and more efficient data retrieval from ontology ABoxes can be attained. To compute such an ABox module, we present a theoretical approach and also an approximation for SHIQ ontologies. Evaluation of the module approximation on different types of ontologies shows that, on average, extracted ABox modules are significantly smaller than the entire ABox, and the time for ontology reasoning based on ABox modules can be improved significantly. PMID- 26848489 TI - Novel Acellular Scaffold Made from Decellularized Schwann Cell Sheets for Peripheral Nerve Regeneration. AB - : Extracellular matrix surrounding Schwann cells and neurons provides critical determinants of cellular phenotype during development as well as essential cues in stimulating and guiding regrowth. Using cell sheet technology, we developed a novel scaffold enriched with native extracellular matrix from Schwann cells. Schwann cells were grown into sheets and layered onto polycaprolactone fibers for support. Upon decellularization of these constructs, extracellular matrix remained with few traces of nucleic acids. This method of deposition of extracellular matrix provided more protein than traditional seeding method after decellularization. Additionally, the isolated matrix supported proliferation of Schwann cells better than covalently bound laminin. The proliferation and differentiation of Schwann cells grown on decellularized sheets were complemented by upregulation of Erbb2 and myelin protein zero. Laminin expression of beta1 and gamma1 chains was also elevated. PC12 cells grown on decellularized sheets produced longer neurite extensions than aligned polycaprolactone fibers alone, proving potential of these scaffolds to be used in future peripheral nerve regenerative studies. LAY SUMMARY: Peripheral nerve injuries present a serious clinical need with approximately 50 % of surgical cases achieving only some restoration of function. In order to better guide regenerating nerves, supporting cells of the nerve tissue were grown into sheets and subsequently decellularized, leaving a myriad of surrounding protein as a scaffold. Constructs have been shown to support cell growth and neurite extension in vitro. Future projects will combine various cell types present in the nerve tissue as well as stem cells to fully support and reconstruct architecture of the peripheral nerves. PMID- 26848491 TI - Towards Understanding the Usage Pattern of Web-based Electronic Medical Record Systems. AB - The benefits and importance of electronic medical record (EMR) systems have been well recognized in the healthcare industry. Yet, their wide adoption still face significant barriers in providing on-demand secure medical information access while preserving patients' privacy. Understanding the usage pattern of an EMR system is the first essential step towards building such environment. This paper conducts an in-depth trace analysis of a large-scale EMR system that has been in operation for more than a decade at the Vanderbilt Medical Center. Our study demonstrates several important characteristics of EMR system usage from the perspective of user-initiated sessions. First, the workload of the EMR system is highly stable and consistent with a weekly pattern. Second, EMR behavior varies between users, but each user's behavior tends to be consistent with a slow rate of migration across sessions. Finally, the degree of access between users and medical records is sparse, echoing the limits of patient-caregiver relationships that manifest in real healthcare operations. We believe these observations can assist in the development of system security measures, such as EMR-specific anomaly detection systems, and facilitate system performance optimization. PMID- 26848493 TI - Retraction. PMID- 26848492 TI - Editorial part 1. PMID- 26848494 TI - Early-stage Alcoholic Cerebellar Degeneration: Diagnostic Imaging Clues. PMID- 26848495 TI - Remote Ischemic Preconditioning and Cardiac Surgery. PMID- 26848496 TI - Counselling: Knowledge is power. PMID- 26848497 TI - CHARACTERISATION OF BACTERIAL ISOLATES FROM PATIENTS WOUNDS AND ENVIRONMENTAL FACTORS PREDICTIVE OF POST-SURGICAL INFECTIONS AT THE ORTHOPAEDIC WARD IN ILE IFE, NIGERIA. AB - OBJECTIVE: To determine the pattern of orthopaedic wound infection and the influence of environmental factors on the distribution of the etiologic bacterial agents. DESIGN: A prospective observational study. SETTING: Department of Orthopaedic Surgery and Traumatology, Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria. SUBJECTS: Sixty patients with orthopaedic wound infections and orthopaedic ward environment. RESULTS: Thirty- nine males (mean age 33.31+2SD) and 21 females (mean age 27.47 + 2SD) with orthopaedic wounds. Three hundred and ten bacteria (190 from patients and 120 from ward environment) were isolated. The pattern of bacterial isolates from patients' wounds was different from that of the airborne bacterial isolates irrespective of the length of stay on the ward. There was a significant difference in the distribution and resistance pattern of bacterial isolates from the patient's wounds and ward environment. CONCLUSION: There is a high incidence of antibiotic resistance of bacterial isolates from samples cultured from patients compared with isolates from ward environment at this centre. The extensive use of pre operative prophylactic and post-surgical antibiotics in various combinations at this centre needs to be re-examined to reduce the preponderance of antibiotic resistance. PMID- 26848498 TI - OUTPATIENT PRESCRIBING PRACTICES AT MBAGATHI DISTRICT HOSPITAL-NAIROBI COUNTY. AB - OBJECTIVE: To assess medicine use practices by using WHO prescribing and patient care indicators in Mbagathi Hospital outpatient department. DESIGN: A hospital based retrospective study. SETTING: Mbagathi District Hospital outpatient department between 1st January to 30th June 2012. MAIN OUTCOME MEASURES: Measures used in this study included, total number of medicines in a prescription, proportion of medicines in the essential drug list, proportion in generic names, proportion with injectables and antibiotics and percentage actually dispensed. RESULTS: Total number of drugs prescribed was 1,506. On average, each patient was prescribed 3.85 types of drugs. A total of 835 drugs were prescribed by generic name, accounting for 25.6% of total number of drugs prescribed (1,506). Out of 391 sampled prescriptions, 266 had antibiotics accounting for (68.0%). A relatively small proportion of the prescriptions, 9.5% had an injection. A total of 1,087 drugs were prescribed according to the essential drugs list or formulary, accounting for 72.2% of total number of drugs prescribed (1,506). Only 55.2% of total medicines prescribed were actually dispensed and the rest were out of stock. CONCLUSION: The prescribing practices in this study are not satisfactory, as suggested by polypharmacy, over prescription of antibiotics, prescribing by brand names and lack of awareness of essential drugs list. PMID- 26848499 TI - COMMUNITY KNOWLEDGE AND PERCEPTIONS ON NATIONAL SCHOOL-BASED DE-WORMING PROGRAMME. AB - OBJECTIVES: To determine the community level of knowledge, attitude and perception of soil transmitted helminthes and the national school-based de worming programme in selected villages of Busia County in Kenya. DESIGN: A cross sectional survey. SETTING: Busia and Bunyala districts in Busia County. SUBJECTS: A total of 384 participants were studied. MAIN OUTCOME MEASURES: Socio demographic characteristics, then knowledge, causes and effects of Soil Transmitted Infections on health and education, prevention strategies, knowledge of national school-based de-worming programs, implementing strategies of the programme, benefits of the programme, community satisfaction and health seeking behaviour. RESULTS: Eating the uncooked food as a cause for soil transmitted infections constituted 27.16% (63) followed by 16.38% (38) notusing latrines, 15.95% (37) eating left over foods, 12.93% (30) eating cold food, 10.78% (25) eating not well cooked pork, 9.48% (22) eating contaminated soil, and 7.33% (17) changing of diet. One head teacher interviewed stated that "One can be able to notice if his/her child has worm infection if the child eats without getting satisfied, eating all the time and yet his belly is big."Community Health Extension Worker in the FGD stated that: "During flood seasons most of the areas in Budalangi become flooded and all latrines are filled with water and the excreta start overflowing. Most of the residents don't have shoes especially the children and therefore they are prone to the worm infection."99.57% of the parents were aware of the national school based de-worming programme of which (92%) learnt about the programme after their children were de-wormed in their various schools. Seventy five percent (174) were satisfied about the programme; 65.1% (151) and 10.3% indicated that the programme improves the children's health and student's school performance respectively. CONCLUSION: Most of the parents do not have adequate knowledge on worms, their causes, and signs and symptoms of the intestinal worms. Low educational levels and poverty levels also contribute to the lack of awareness on intestinal worms and putting the prevention measures across the board. The study also found out that the community perception towards the de-worming programme was good because the de-worming programme improved the children's health and performance in school. PMID- 26848501 TI - NEGATIVE PRESSURE WOUND THERAPY (NPWT) FOR THE MANAGEMENT OF LAPAROSTOMY WOUNDS: CASE SERIES. AB - Laparostomy or the open abdomen can be a lifesaving intervention in surgical emergencies for abdominal compartment syndrome, wound dehiscence, trauma and intra-abdominal sepsis. However, the open abdomen imposes a significant burden on nursing staff caring for these critically ill patients due to the large volume of exudate and fluid loss.To achieve mechanical containment of abdominal viscera and active removal of exudate, we used NPWT to manage five patients with complex intra-abdominal sepsis laparostomy wounds. It took between 12 to 28 days to achieve full granulation for secondary closure of the wounds. The series shows that in the management of laparostomy wounds, NPWT provides an easier way to manage the large volumes of exudates and reduces the frequency of dressings changes required with traditional wound dressings. PMID- 26848500 TI - CIVILIAN VASCULAR INJURIES IN AN URBAN AFRICAN REFERRAL INSTITUTION. AB - OJECTIVE: To evaluate the pattern of civilian vascular injuries, demonstrate any change in pattern and document management challenges in a resource challenged environment. DESIGN: A retrospective study. SETTING: The division of Thoracic and Cardiovascular Surgery of University College Hospital a major referral centre, not only for south-west Nigeria but for the whole country. SUBJECTS: All patients presenting with vascular injury through the division during the study period were recruited. There were no exclusion criteria. RESULTS: Males accounted for 85% of the study group. Mean age was 31.98 years (+/- 14.94 S.D.) with peak in 20-29 years group (28.3%). Stab and gunshot injury were responsible in 36.7% and 30% respectively. Upper limb vessels were involved in 58.3%. Delayed presentation (> 4 hrs postinjury) occurred in 58.3% and presentation-operation interval was four to six hours in 55% of cases. Specific diagnostic investigation was required in only 20%. Morbidity, amputation and mortality rates were 10.1, 3 and 6.7% respectively. CONCLUSION: Penetrating vascular injuries are on the increase amongst civilian population. Poor transportation and lack of organised referral system contribute to delay in surgical intervention. Prompt evaluation for hard signs of vascular injury is of immense value in deciding for surgery in our environment where patients have financial challenges and resources are limited. PMID- 26848502 TI - Gelsolin rs1078305 and rs10818524 polymorphisms were associated with risk of oral squamous cell carcinoma in a Chinese Han population. AB - BACKGROUND: Gelsolin (GSN) is one of the most abundant actin-binding proteins, and is involved in cancer development and progression. PATIENTS AND METHODS: A hospital-based case-control study including 201 patients with OSCC and 199 healthy controls was conducted. Seventeen single-nucleotide polymorphisms (SNPs) of GSN were investigated by Sequenom Mass ARRAY and iPLEX-MALDI-TOF technology. RESULTS: Through comparison of the 17 SNPs on GSN gene between the two groups, SNP rs1078305 and rs10818524 were verified to be significantly associated with an increased risk of OSCC. For GSN rs1078305, the TT genotype was associated with increased risk for OSCC (OR = 1.92, 95% CI = 1.11-3.32, p = 0.028). CT/TT variants were also associated with increased risk for OSCC compared to the CC genotype (OR = 1.83, 95% CI = 1.25-3.84, p = 0.032). CONCLUSION: The rs1078305 and rs10818524 SNPs of GSN were associated with increased risk for OSCC development in a Chinese Han population. PMID- 26848504 TI - Anti-hepatitis C Virus Natural Product from a Fungus, Penicillium herquei. AB - New diazabicyclo[2.2.2]octane derivatives, peniciherquamides A-C (1-3), and a novel herqueinone derivative, neoherqueinone (5), were isolated from a fungal culture broth of Penicillium herquei. The structures of these novel compounds were determined by interpretation of spectroscopic data (1D/2D NMR, MS, and IR). Four known compounds, preparaherquamide (4), peniciherqueinone (6), and herqueinone/isoherqueinone (7/7a), were also obtained. The isolated compounds were tested for anti-hepatitis C virus (HCV) activity, and peniciherquamide C (3) was found to display an IC50 value of 5.1 MUM. To our knowledge, this is the first report of a diazabicyclo[2.2.2]octane derivative with anti-HCV activity. PMID- 26848505 TI - Edge-Modified Phosphorene Nanoflake Heterojunctions as Highly Efficient Solar Cells. AB - We propose to use edge-modified phosphorene nanoflakes (PNFs) as donor and acceptor materials for heterojunction solar cells. By using density functional theory based calculations, we show that heterojunctions consisting of hydrogen- and fluorine-passivated PNFs have a number of desired optoelectronic properties that are suitable for use in a solar cell. We explain why these properties hold for these types of heterojunctions. Our calculations also predict that the maximum energy conversion efficiency of these type of heterojunctions, which can be easily fabricated, can be as high as 20%, making them extremely competitive with other types of two-dimensional heterojunctions. PMID- 26848503 TI - Mapping and Exploring the Collagen-I Proteostasis Network. AB - Collagen-I is the most abundant protein in the human body, yet our understanding of how the endoplasmic reticulum regulates collagen-I proteostasis (folding, quality control, and secretion) remains immature. Of particular importance, interactomic studies to map the collagen-I proteostasis network have never been performed. Such studies would provide insight into mechanisms of collagen-I folding and misfolding in cells, an area that is particularly important owing to the prominence of the collagen misfolding-related diseases. Here, we overcome key roadblocks to progress in this area by generating stable fibrosarcoma cells that inducibly express properly folded and modified collagen-I strands tagged with distinctive antibody epitopes. Selective immunoprecipitation of collagen-I from these cells integrated with quantitative mass spectrometry-based proteomics permits the first mapping of the collagen-I proteostasis network. Biochemical validation of the resulting map leads to the assignment of numerous new players in collagen-I proteostasis, and the unanticipated discovery of apparent aspartyl hydroxylation as a new post-translational modification in the N-propeptide of collagen-I. Furthermore, quantitative analyses reveal that Erp29, an abundant endoplasmic reticulum proteostasis machinery component with few known functions, plays a key role in collagen-I retention under ascorbate-deficient conditions. In summary, the work here provides fresh insights into the molecular mechanisms of collagen-I proteostasis, yielding a detailed roadmap for future investigations. Straightforward adaptations of the cellular platform developed will also enable hypothesis-driven, comparative research on the likely distinctive proteostasis mechanisms engaged by normal and disease-causing, misfolding collagen-I variants, potentially motivating new therapeutic strategies for currently incurable collagenopathies. PMID- 26848506 TI - Real-Time Fluorescence Tracking of Protoporphyrin Incorporated Thermosensitive Hydrogel and Its Drug Release in Vivo. AB - Fluorescence imaging in vivo will pave an important way for the evaluation of biomaterials. The major advantage of fluorescence imaging compared to other imaging modalities is the possibility of tracking two or more fluorescence probes simultaneously with multispectral fluorescence imaging. It is essential to elucidate the location, erosion, drug release and resection of implanted biomaterials in vivo. Herein, a thermosensitive hydrogel with a protoporphyrin core based on a PEG and PCL copolymer (PCL-PEG-PPOR-PEG-PCL) was synthesized by ring-opening polymerization using protoporphyrin as a fluorescence tag. The optical properties of the hydrogel were investigated by UV-vis and fluorescence spectroscopy in vitro and by fluorescence imaging system in vivo. The hydrogel erosion and drug delivery in vivo were monitored and tracked by multispectral fluorescence imaging system in nude mice. The results show that the thermosensitive hydrogel exhibits fluorescence and injectability in vivo with good biocompatibility. Through the modality of fluorescence imaging, the status of the hydrogel is reflected in situ in vivo including its location and erosion. Multispectral analysis separates the autofluorescence signals from the specific label and provides the ability to locate the drug and carrier. The protoporphyrin incorporated thermosensitive hydrogel can be a potential visiable biomedical implant for tissue repair or drug delivery. PMID- 26848507 TI - Acridine Orange Conjugated Polymersomes for Simultaneous Nuclear Delivery of Gemcitabine and Doxorubicin to Pancreatic Cancer Cells. AB - Considering the systemic toxicity of chemotherapeutic agents, there is an urgent need to develop new targeted drug delivery systems. Herein, we have developed a new nuclear targeted, redox sensitive, drug delivery vehicle to simultaneously deliver the anticancer drugs gemcitabine and doxorubicin to the nuclei of pancreatic cancer cells. We prepared polymeric bilayer vesicles (polymersomes), and actively encapsulated the drug combination by the pH gradient method. A redox sensitive polymer (PEG-S-S-PLA) was incorporated to sensitize the formulation to reducing agent concentration. Acridine orange (AO) was conjugated to the surface of the polymersomes imparting nuclear localizing property. The polymersomes' toxicity and efficacy were compared with those of a free drug combination using monolayer and three-dimensional spheroid cultures of pancreatic cancer cells. We observed that the redox sensitive, nuclear-targeted polymersomes released more than 60% of their encapsulated contents in response to 50 mM glutathione. The nanoparticles are nontoxic; however, the drug encapsulated vesicles have significant toxicity. The prepared formulation can increase the drug's therapeutic index by delivering the drugs directly to the cells' nuclei, one of the key organelles in the cells. This study is likely to initiate research in targeted nuclear delivery using other drug formulations in other types of cancers. PMID- 26848508 TI - Structural and Spectroscopic Characterizations of Amide-AlCl3-Based Ionic Liquid Analogues. AB - Several amide-AlCl3-based ionic liquid (IL) analogues were synthesized through a one-step method using three different structure amides as donor molecules. The effects of the steric and inductive effects of the methyl group substituted on the N atom on the asymmetric splitting of AlCl3 and the coordination site of the amide were investigated by (27)Al NMR, Raman, in situ IR, and UV-vis spectra for these IL analogues. Bidentate coordination through both the O and N atoms was dominant in the N-methylacetamide-AlCl3- and N,N-dimethylacetamide-AlCl3-based IL analogues because of the inductive effect of the methyl group. By contrast, the acetamide-AlCl3-based IL analogue presented mainly in the form of monodentate coordination via the O atom. Compared with monodentate coordination, bidentate coordination was favorable to the asymmetric splitting of AlCl3 with the same amide-AlCl3 molar ratio. Under the influence of the steric and inductive effects of the methyl group, the ionic species percentages in these IL analogues ranked in the following order: N-methylacetamide > N,N-dimethylacetamide > acetamide. PMID- 26848509 TI - The presence of thin glomerular basement membranes in various glomerulopathies. AB - Results of 61 cases of various glomerulopathies with thin glomerular basement membranes are presented. The largest group of 31 cases consisted of mesangial glomerulonephritis. The second largest group consisted of 19 patients with small glomerular lesions described as non-specific. This group stood out in both clinical presentations and in the higher diversity of lesions within the lamina densa of the basement membrane. The results of measurements of the lamina densa in various glomerulopathies were compared to those obtained in control groups consisting of thin basement membrane syndrome and submicroscopic glomerulonephritis. PMID- 26848510 TI - Structure-Kinetics Correlations in Isostructural Crystals of alpha-(ortho-Tolyl) acetophenones: Pinning Down Electronic Effects Using Laser-Flash Photolysis in the Solid State. AB - Aqueous suspensions of nanocrystals in the 200-500 nm size range of isostructural alpha-(ortho-tolyl)-acetophenone (1a) and alpha-(ortho-tolyl)-para methylacetophenone (1b) displayed good absorption characteristics for flash photolysis experiments in a flow system, with transient spectra and decay kinetics with a quality that is similar to that recorded in solution. In contrast to solution measurements, reactions in the solid state were characterized by a rate limiting hydrogen transfer reaction from the triplet excited state and a very short-lived biradical intermediate, which does not accumulate. Notably, the rate for delta-hydrogen atom transfer of 1a (2.7 * 10(7) s(-1)) in the crystalline phase is 18-fold larger than that of 1b (1.5 * 10(6) s(-1)). With nearly identical molecular and crystal structures, this decrease in the rate of delta-hydrogen abstraction can be assigned unambiguously to an electronic effect by the para-methyl group in 1b, which increases the contribution of the (3)pi,pi* configuration relative to the reactive (3)n,pi* configuration in the lowest triplet excited state. These results highlight the potential of relating single crystal X-ray structural data with absolute kinetics from laser flash photolysis. PMID- 26848512 TI - Diagnostics and susceptibility testing in Aspergillus. AB - Invasive aspergillosis is a major cause of morbidity and mortality in immunosuppressed patients. Early diagnosis and correct antifungal treatment have a direct impact on patient survival. A number of newer diagnostic procedures have been developed as alternatives to conventional microbiological methods. The detection of fungal components, largely antigens and DNA, are used in clinical laboratories to diagnose invasive aspergillosis. Other rapid diagnostic tests have been recently developed with promising results. However, antifungal resistance is becoming an emerging problem. The detection of this resistance is important to administer the proper antifungal agent. This text reviews the novelties on new diagnostics Aspergillus spp. PROCEDURES: Intrinsic antifungal resistance and mechanisms of secondary resistance to triazoles in A. fumigatus are also reviewed. PMID- 26848511 TI - Discovery of Novel Nonactive Site Inhibitors of the Prothrombinase Enzyme Complex. AB - The risk of serious bleeding is a major liability of anticoagulant drugs that are active-site competitive inhibitors targeting the Factor Xa (FXa) prothrombin (PT) binding site. The present work identifies several new classes of small molecule anticoagulants that can act as nonactive site inhibitors of the prothrombinase (PTase) complex composed of FXa and Factor Va (FVa). These new classes of anticoagulants were identified, using a novel agnostic computational approach to identify previously unrecognized binding pockets at the FXa-FVa interface. From about three million docking calculations of 281,128 compounds in a conformational ensemble of FXa heavy chains identified by molecular dynamics (MD) simulations, 97 compounds and their structural analogues were selected for experimental validation, through a series of inhibition assays. The compound selection was based on their predicted binding affinities to FXa and their ability to successfully bind to multiple protein conformations while showing selectivity for particular binding sites at the FXa/FVa interface. From these, thirty-one (31) compounds were experimentally identified as nonactive site inhibitors. Concentration-based assays further identified 10 compounds represented by four small-molecule families of inhibitors that achieve dose-independent partial inhibition of PTase activity in a nonactive site-dependent and self-limiting mechanism. Several compounds were identified for their ability to bind to protein conformations only seen during MD, highlighting the importance of accounting for protein flexibility in structure-based drug discovery approaches. PMID- 26848513 TI - Drivers of MERS-CoV transmission: what do we know? AB - Middle East Respiratory Syndrome coronavirus (MERS-CoV) emerged in 2012 has since resulted in sporadic cases, intra-familial transmission and major outbreaks in healthcare settings. The clinical picture of MERS-CoV includes asymptomatic infections, mild or moderately symptomatic cases and fatal disease. Transmissions of MERS-CoV within healthcare settings are facilitated by overcrowding, poor compliance with basic infection control measures, unrecognized infections, the superspreaders phenomenon and poor triage systems. The actual contributing factors to the spread of MERS-CoV are yet to be systematically studied, but data to date suggest viral, host and environmental factors play a major role. Here, we summarize the known factors for the diverse transmission of MERS-CoV. PMID- 26848514 TI - Hazardous alcohol use and cultural adjustment among U.S. college students abroad in Italy: Findings and recommendations for study abroad staff and researchers. AB - BACKGROUND: Italy is a top destination for U.S. college students studying abroad. Both international and local Italian media outlets, such as city newspapers, have cited the discordance between Italian cultural norms and U.S. college students' drinking behaviors. Hazardous alcohol consumption abroad, such as binge drinking, can result in individual- (e.g., physical injury) and social- (e.g., promotion of negative stereotypes) level adverse consequences. METHODS: We assessed the prevalence of hazardous alcohol use and recent binge drinking in a sample of U.S. college students studying abroad in Italy (n = 111). We evaluated associations among drinking and cultural adjustment and determined which sociocultural factors predicted binge drinking for students abroad. RESULTS: Forty-six percent of students were classified as hazardous drinkers and 63% reported recent binge drinking. Socializing with American peers was a significant predictor for binge drinking abroad. CONCLUSIONS: Binge drinking was quite prevalent in our sample of students studying abroad in Italy. Study abroad advisors, instructors, and staff should consider diverse strategies to screen, educate, prevent, and/or intervene on alcohol misuse with their students. These strategies should be personalized to both the student as well as the host culture's norms. PMID- 26848515 TI - Distribution and Dynamic Properties of Xenon Dissolved in the Ionic Smectic Phase of [C16mim][NO3]: MD Simulation and Theoretical Model. AB - We have investigated the structural and dynamic properties of Xe dissolved in the ionic liquid crystal (ILC) phase of 1-hexadecyl-3-methylimidazolium nitrate using classical molecular dynamics (MD) simulations. Xe is found to be preferentially dissolved within the hydrophobic environment of the alkyl chains rather than in the ionic layers of the smectic phase. The structural parameters and the estimated local diffusion coefficients concerning the short-time motion of Xe are used to parametrize a theoretical model based on the Smoluchowski equation for the macroscopic dynamics across the smectic layers, a feature which cannot be directly obtained from the relatively short MD simulations. This protocol represents an efficient combination of computational and theoretical tools to obtain information on slow processes concerning the permeability and diffusivity of the xenon in smectic ILCs. PMID- 26848517 TI - An online guided ACT intervention for enhancing the psychological wellbeing of university students: A randomized controlled clinical trial. AB - Stress, anxiety and depression are relatively common problems among university students. This study examined whether an online psychological intervention aiming at enhancing the wellbeing of university students could be an effective and practical alternative for meeting the needs of a university population. University students (N = 68; 85% female; 19-32 years old) were randomly assigned to either a guided seven-week online Acceptance and Commitment Therapy (iACT) intervention or a waiting list control condition (WLC). A between-groups pre-post (iACT vs WLC) design with 12-month follow-up for the iACT participants was conducted. The intervention participants were offered two face-to-face meetings, completed online exercises during a five-week period, and received personal weekly written feedback via the website from their randomly assigned, trained student coaches. Waitlist participants were offered the intervention program soon after the post measurements. Results in this small efficacy trial showed that the iACT participants had significantly higher gains in wellbeing (between group, d = 0.46), life satisfaction (d = 0.65), and mindfulness skills (d = 0.49). In addition, iACT participants' self-reported stress (d = 0.54) and symptoms of depression (d = 0.69) were significantly reduced compared to the participants in the control group. These benefits were maintained over a 12-month follow-up period (within iACT group, d = 0.65-0.69, for primary measures). The results suggest that an online-based, coach-guided ACT program with blended face-to-face and online sessions could be an effective and well-accepted alternative for enhancing the wellbeing of university students. PMID- 26848516 TI - Role of Linear Ubiquitination in Health and Disease. AB - The covalent attachment of ubiquitin to target proteins is one of the most prevalent post-translational modifications, regulating a myriad of cellular processes including cell growth, survival, and metabolism. Recently, a novel RING E3 ligase complex was described, called linear ubiquitin assembly complex (LUBAC), which is capable of connecting ubiquitin molecules in a novel head-to tail fashion via the N-terminal methionine residue. LUBAC is a heteromeric complex composed of heme-oxidized iron-responsive element-binding protein 2 ubiquitin ligase-1L (HOIL-1L), HOIL-1L-interacting protein, and shank-associated RH domain-interacting protein (SHARPIN). The essential role of LUBAC-generated linear chains for activation of nuclear factor-kappaB (NF-kappaB) signaling was first described in the activation of tumor necrosis factor-alpha receptor signaling complex. A decade of research has identified additional pathways that use LUBAC for downstream signaling, including CD40 ligand and the IL-1beta receptor, as well as cytosolic pattern recognition receptors including nucleotide binding oligomerization domain containing 2 (NOD2), retinoic acid-inducible gene 1 (RIG-1), and the NOD-like receptor family, pyrin domain containing 3 inflammasome (NLRP3). Even though the three components of the complex are required for full activation of NF-kappaB, the individual components of LUBAC regulate specific cell type- and stimuli-dependent effects. In humans, autosomal defects in LUBAC are associated with both autoinflammation and immunodeficiency, with additional disorders described in mice. Moreover, in the lung epithelium, HOIL-1L ubiquitinates target proteins independently of the other LUBAC components, adding another layer of complexity to the function and regulation of LUBAC. Although many advances have been made, the diverse functions of linear ubiquitin chains and the regulation of LUBAC are not yet completely understood. In this review, we discuss the various roles of linear ubiquitin chains and point to areas of study that would benefit from further investigation into LUBAC mediated signaling pathways in lung pathophysiology. PMID- 26848519 TI - Novel Strategies for Applied Metagenomics. AB - Detailed analyses of the gut microbiome and its effect on human physiology and disease are emerging, thanks to advances in high-throughput DNA-sequencing technology and the burgeoning field of metagenomics. Metagenomics examines the structure and functional potential of microbial communities in their native habitats through the direct isolation and analysis of community DNA. In inflammatory bowel disease, gut microbiome studies have shown an association with perturbations in community composition and, especially, function. In this review, we discuss the application of next-generation sequencing to microbiome research and highlight the importance of modeling microbiome structure and function to the future of inflammatory bowel disease research and treatment. PMID- 26848518 TI - Decreased Fibrogenesis After Treatment with Pirfenidone in a Newly Developed Mouse Model of Intestinal Fibrosis. AB - BACKGROUND: Fibrosis as a common problem in patients with Crohn's disease is a result of an imbalance toward excessive tissue repair. At present, there is no specific treatment option. Pirfenidone is approved for the treatment of idiopathic pulmonary fibrosis with both antifibrotic and anti-inflammatory effects. We subsequently investigated the impact of pirfenidone treatment on development of fibrosis in a new mouse model of intestinal fibrosis. METHODS: Small bowel resections from donor mice were transplanted subcutaneously into the neck of recipients. Animals received either pirfenidone (100 mg/kg, three times daily, orally) or vehicle. RESULTS: After administration of pirfenidone, a significantly decreased collagen layer thickness was revealed as compared to vehicle (9.7 +/- 1.0 versus 13.5 +/- 1.5 um, respectively, **P < 0.001). Transforming growth factor-beta and matrix metalloproteinase-9 were significantly decreased after treatment with pirfenidone as confirmed by real-time PCR (0.42 +/ 0.13 versus 1.00 +/- 0.21 and 0.46 +/- 0.24 versus 1.00 +/- 0.62 mRNA expression level relative to GAPDH, respectively, *P < 0.05). Significantly decreased transforming growth factor-beta after administration of pirfenidone was confirmed by Western blotting. CONCLUSION: In our mouse model, intestinal fibrosis can be reliably induced and is developed within 7 days. Pirfenidone partially prevented the development of fibrosis, making it a potential treatment option against Crohn's disease-associated fibrosis. PMID- 26848520 TI - Systematic review on tuberculosis transmission on aircraft and update of the European Centre for Disease Prevention and Control risk assessment guidelines for tuberculosis transmitted on aircraft (RAGIDA-TB). AB - As a setting for potential tuberculosis (TB) transmission and contact tracing, aircraft pose specific challenges. Evidence-based guidelines are needed to support the related-risk assessment and contact-tracing efforts. In this study evidence of TB transmission on aircraft was identified to update the Risk Assessment Guidelines for TB Transmitted on Aircraft (RAGIDA-TB) of the European Centre for Disease Prevention and Control (ECDC). Electronic searches were undertaken from Medline (Pubmed), Embase and Cochrane Library until 19 July 2013. Eligible records were identified by a two-stage screening process and data on flight and index case characteristics as well as contact tracing strategies extracted. The systematic literature review retrieved 21 records. Ten of these records were available only after the previous version of the RAGIDA guidelines (2009) and World Health Organization guidelines on TB and air travel (2008) were published. Seven of the 21 records presented some evidence of possible in-flight transmission, but only one record provided substantial evidence of TB transmission on an aircraft. The data indicate that overall risk of TB transmission on aircraft is very low. The updated ECDC guidelines for TB transmission on aircraft have global implications due to inevitable need for international collaboration in contract tracing and risk assessment. PMID- 26848521 TI - Helicobacter pylori CagA induces tumor suppressor gene hypermethylation by upregulating DNMT1 via AKT-NFkappaB pathway in gastric cancer development. AB - Methylation of CpG islands in tumor suppressor gene prompter is one of the most characteristic abnormalities in Helicobacter pylori (HP)-associated gastric carcinoma (GC). Here, we investigated the pathogenic and molecular mechanisms underlying hypermethylation of tumor suppressor genes in HP induced GC development. We found that tumor suppressor genes hypermethylation, represented by MGMT, positively correlated with CagA in clinical specimens, gastric tissues from HP infected C57 mice and GC cell lines transfected by CagA or treated by HP infection. CagA enhanced PDK1 and AKT interaction and increased AKT phosphorylation. The P-AKT subsequent activated NFkappaB, which then bound to DNMT1 promoter and increased its expression. Finally, the upregulated DNMT1 promoted tumor suppressor genes hypermethylation with MGMT as a representative. In conclusion, CagA increased tumor suppressor genes hypermethylation via stimulating DNMT1 expression through the AKT-NFkappaB pathway. PMID- 26848522 TI - The transcription factor GATA1 and the histone methyltransferase SET7 interact to promote VEGF-mediated angiogenesis and tumor growth and predict clinical outcome of breast cancer. AB - Angiogenesis is essential for tumor growth. Vascular endothelial growth factor (VEGF) is the most important regulator of tumor angiogenesis. However, how transcription factors interact with histone-modifying enzymes to regulate VEGF transcription and tumor angiogenesis remains unclear. Here, we show that transcription factor GATA1 associates with the histone methyltransferase SET7 to promote VEGF transcription and breast tumor angiogenesis. Using chromatin immunoprecipitation assay, we found that GATA1 was required for recruitment of SET7, RNA polymerase II and transcription factor II B to VEGF core promoter. GATA1 enhanced breast cancer cell (MCF7, ZR75-1 and MDA-MB-231)-secreted VEGF via SET7, which promoted vascular endothelial cell (HUVEC) proliferation, migration and tube formation. SET7 was required for GATA1-induced breast tumor angiogenesis and growth in nude mice. Immunohistochemical staining showed that expression of GATA1 and SET7 was upregulated and positively correlated with VEGF expression and microvessel number in 80 breast cancer patients. GATA1 and SET7 are independent poor prognostic factors in breast cancer. Our data provide novel insights into VEGF transcriptional regulation and suggest GATA1/SET7 as cancer therapeutic targets. PMID- 26848523 TI - Identifying molecular genetic features and oncogenic pathways of clear cell renal cell carcinoma through the anatomical (PADUA) scoring system. AB - Although the preoperative aspects and dimensions used for the PADUA scoring system were successfully applied in macroscopic clinical practice for renal tumor, the relevant molecular genetic basis remained unclear. To uncover meaningful correlations between the genetic aberrations and radiological features, we enrolled 112 patients with clear cell renal cell carcinoma (ccRCC) whose clinicopathological data, genomics data and CT data were obtained from The Cancer Genome Atlas (TCGA) and The Cancer Imaging Archive (TCIA). Overall PADUA score and several radiological features included in the PADUA system were assigned for each ccRCC. Despite having observed no significant association between the gene mutation frequency and the overall PADUA score, correlations between gene mutations and a few radiological features (tumor rim location and tumor size) were identified. A significant association between rim location and miRNA molecular subtypes was also observed. Survival analysis revealed that tumor size > 7 cm was significantly associated with poor survival. In addition, Gene Set Enrichment Analysis (GSEA) on mRNA expression revealed that the high PADUA score was related to numerous cancer-related networks, especially epithelial to mesenchymal transition (EMT) related pathways. This preliminary analysis of ccRCC revealed meaningful correlations between PADUA anatomical features and molecular basis including genomic aberrations and molecular subtypes. PMID- 26848524 TI - Inhibiting receptor tyrosine kinase AXL with small molecule inhibitor BMS-777607 reduces glioblastoma growth, migration, and invasion in vitro and in vivo. AB - PURPOSE: Receptor tyrosine kinase AXL (RTK-AXL) is regarded as suitable target in glioma therapy. Here we evaluate the anti-tumoral effect of small molecule inhibitor BMS-777607 targeting RTK-AXL in a preclinical glioma model and provide evidence that RTK-AXL is expressed and phosphorylated in primary and recurrent glioblastoma multiforme (GBM). EXPERIMENTAL DESIGN: We studied the impact of BMS 777607 targeting RTK-AXL in GBM models in vitro and in vivo utilizing glioma cells SF126 and U118MG. Impact on proliferation, apoptosis and angiogenesis was investigated by immunohistochemistry (IHC) and functional assays in vitro and in vivo. Tumor growth was assessed with MRI. Human GBM tissue was analyzed in terms of RTK-AXL phosphorylation by immunoprecipitation and immunohistochemistry. RESULTS: BMS-777607 displayed various anti-cancer effects dependent on increased apoptosis, decreased proliferation and migration in vitro and ex vivo in SF126 and U118 GBM cells. In vivo we observed a 56% tumor volume reduction in SF126 xenografts and remission in U118MG xenografts of more than 91%. The tube formation assay confirmed the anti-angiogenic effect of BMS-777607, which became also apparent in tumor xenografts. IHC of human GBM tissue localized phosphorylated RTK-AXL in hypercellular tumor regions, the migratory front of tumor cells in pseudo-palisades, and in vascular proliferates within the tumor. We further proved RTK-AXL phosphorylation in primary and recurrent disease state. CONCLUSION: Collectively, these data strongly suggest that targeting RTK-AXL with BMS-777607 could represent a novel and potent regimen for the treatment of primary and recurrent GBM. PMID- 26848525 TI - Stereotactic radiosurgery (SRS) in the modern management of patients with brain metastases. AB - Stereotactic radiosurgery (SRS) is an established non-invasive ablative therapy for brain metastases. Early clinical trials with SRS proved that tumor control rates are superior to whole brain radiotherapy (WBRT) alone. As a result, WBRT plus SRS was widely adopted for patients with a limited number of brain metastases ("limited number" customarily means 1-4). Subsequent trials focused on answering whether WBRT upfront was necessary at all. Based on current randomized controlled trials (RCTs) and meta-analyses comparing SRS alone to SRS plus WBRT, adjuvant WBRT results in better intracranial control; however, at the expense of neurocognitive functioning and quality of life. These adverse effects of WBRT may also negatively impact on survival in younger patients. Based on the results of these studies, treatment has shifted to SRS alone in patients with a limited number of metastases. Additionally, RCTs are evaluating the role of SRS alone in patients with >4 brain metastases. New developments in SRS include fractionated SRS for large tumors and the integration of SRS with targeted systemic therapies that cross the blood brain barrier and/or stimulate an immune response. We present in this review the current high level evidence and rationale supporting SRS as the standard of care for patients with limited brain metastases, and emerging applications of SRS. PMID- 26848526 TI - Oncogenic K-ras confers SAHA resistance by up-regulating HDAC6 and c-myc expression. AB - Histone deacetylase inhibitors (HDIs) represent a new class of anticancer drugs. Suberoylanilide hydroxamic acid (SAHA), the first HDI approved for the treatment of cutaneous T cell lymphoma (CTCL), is currently being tested in clinical trials for other cancers. However, SAHA has been ineffective against solid tumors in many clinical trials. A better understanding of molecular mechanisms of SAHA resistance may provide the basis for improved patient selection and the enhancement of clinical efficacy. Here we demonstrate that oncogenic K-ras contributes to SAHA resistance by upregulating HDAC6 and c-myc expression. We find that the high levels of HDAC6 expression are associated with activated K-ras mutant in colon cancer patients. And expressions of HDAC6 and c-myc are increased in fibroblasts transformed with activated K-ras. Surprisingly, we find that activated K-ras transformed cells are more resistant to SAHA inhibition on cell growth and anchorage-independent colony formation. We show that a K-ras inhibitor sensitizes K-ras mutated lung cancer cells to SAHA induced growth inhibition. We also find that mutant K-ras induces HDAC6 expression by a MAP kinase dependent pathway. Our study suggests that combined treatment with SAHA and K-ras inhibitors may represent an effective strategy to overcome SAHA resistance. PMID- 26848527 TI - DDRI-9: a novel DNA damage response inhibitor that blocks mitotic progression. AB - The DNA damage response (DDR) is an emerging target for cancer therapy. By modulating the DDR, including DNA repair and cell cycle arrest, the efficacy of anticancer drugs can be enhanced and side effects reduced. We previously screened a chemical library and identified novel DDR inhibitors including DNA damage response inhibitor-9 (DDRI-9; 1H-Purine-2,6-dione,7-[(4-fluorophenyl)methyl]-3,7 dihydro-3-methyl-8-nitro). In this study, we characterized DDRI-9 activity and found that it inhibited phosphorylated histone variant H2AX foci formation upon DNA damage, delayed DNA repair, and enhanced the cytotoxicity of etoposide and ionizing radiation. It also reduced the foci formation of DNA repair-related proteins, including the protein kinase ataxia-telangiectasia mutated, DNA dependent protein kinase, breast cancer type 1 susceptibility protein, and p53 binding protein 1, but excluding mediator of DNA damage checkpoint protein 1. Cell cycle analysis revealed that DDRI-9 blocked mitotic progression. Like other mitotic inhibitors, DDRI-9 treatment resulted in the accumulation of mitotic protein and induced cell death. Thus, DDRI-9 may affect both DDR signal amplification and mitotic progression. This study suggests that DDRI-9 is a good lead molecule for the development of anticancer drugs. PMID- 26848528 TI - PSCA polymorphisms and gastric cancer susceptibility in an eastern Chinese population. AB - The prostate stem cell antigen (PSCA) gene, which encodes a prostate-specific antigen (PSA), was identified as a gene involved in cell adhesion and proliferation. The associations between the PSCA rs2294008 and rs2976392 single nucleotide polymorphisms (SNPs) and gastric cancer (GCa) susceptibility were still controversial. To derive a more precise estimation of the associations, we conducted a case-control study of 1,124 cases and 1,192 controls in an eastern Chinese population. We found that the rs2294008T variant genotypes were associated with an increased GCa risk in this study population (CT vs CC, OR=1.59, 95% CI=1.33-1.89 and CT+TT vs CC, OR=1.38, 95% CI=1.17-1.62). For SNP rs2976392, the variant A genotypes were also associated with an increased GCa risk (AG vs GG, OR=1.61, 95% CI=1.35-1.91 and AG+AA vs GG, OR=1.47, 95% CI=1.25 1.74). The results were further validated by a meta-analysis. In conclusion, the results indicated that the PSCA rs2294008 T and rs2976392 A alleles were low penetrate risk factors for GCa in this study population. However, large and well designed studies are warranted to validate our findings. PMID- 26848529 TI - Prevalence and spectrum of BRCA germline variants in mainland Chinese familial breast and ovarian cancer patients. AB - Germline mutations in BRCA1 and BRCA2 are the most penetrating genetic predispositions for breast and ovarian cancer, and their presence is largely ethnic-specific. Comprehensive information about the prevalence and spectrum of BRCA mutations has been collected in European and North American populations. However, similar information is lacking in other populations, including the mainland Chinese population despite its large size of 1.4 billion accounting for one fifth of the world's population. Herein, we performed an extensive literature analysis to collect BRCA variants identified from mainland Chinese familial breast and ovarian cancer patients. We observed 137 distinct BRCA1 variants in 409 of 3,844 and 80 distinct BRCA2 variants in 157 of 3,024 mainland Chinese patients, with an estimated prevalence of 10.6% for BRCA1 and 5.2% for BRCA2. Of these variants, only 40.3% in BRCA1 and 42.5% in BRCA2 are listed in current Breast Cancer Information Core database. We observed higher frequent variation in BRCA1 exons 11A, 11C, 11D, and 24 and BRCA2 exon 10 in Chinese patients than in the patients of other populations. The most common pathogenic variant in BRCA1 wasc.981_982delAT in exon 11A, and in BRCA2 c.3195_3198delTAAT in exon 11B and c.5576_5579delTTAA in exon 11E; the most common novel variant in BRCA1 was c.919A>G in exon 10A, and in BRCA2 c.7142delC in exon 14. None of the variants overlap with the founder mutations in other populations. Our analysis indicates that the prevalence of BRCA variation in mainland Chinese familial breast and ovarian cancer patients is at a level similar to but the spectrum is substantially different from the ones of other populations. PMID- 26848530 TI - Human plasma metabolomics for identifying differential metabolites and predicting molecular subtypes of breast cancer. AB - PURPOSE: This work aims to identify differential metabolites and predicting molecular subtypes of breast cancer (BC). METHODS: Plasma samples were collected from 96 BC patients and 79 normal participants. Metabolic profiles were determined by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry based on multivariate statistical data analysis. RESULTS: We observed 64 differential metabolites between BC and normal group. Compared to human epidermal growth factor receptor 2 (HER2)-negative patients, HER2-positive group showed elevated aerobic glycolysis, gluconeogenesis, and increased fatty acid biosynthesis with reduced Krebs cycle. Compared with estrogen receptor (ER) negative group, ER-positive patients showed elevated alanine, aspartate and glutamate metabolism, decreased glycerolipid catabolism, and enhanced purine metabolism. A panel of 8 differential metabolites, including carnitine, lysophosphatidylcholine (20:4), proline, alanine, lysophosphatidylcholine (16:1), glycochenodeoxycholic acid, valine, and 2-octenedioic acid, was identified for the classification of BC subtypes. These markers showed potential diagnostic value with average area under the curve at 0.925 (95% CI 0.867-0.983) for the training set (n=51) and 0.893 (95% CI 0.847-0.939) for the test set (n=45). CONCLUSION: Human plasma metabolomics is useful in identifying differential metabolites and predicting breast cancer subtypes. PMID- 26848532 TI - Skin penetration and antioxidant effect of cosmeto-textiles with gallic acid. AB - In this work, the antioxidant gallic acid (GA) has been encapsulated in microspheres prepared with poly-epsilon-caprolactone (PCL) and incorporated into polyamide (PA) obtaining the cosmeto-textile. The topical application of the cosmeto-textile provides a reservoir effect in the skin delivery of GA. The close contact of the cosmeto-textile, containing microsphere-encapsulated GA (ME-GA), with the skin and their corresponding occlusion, may be the main reasons that explain the crossing of active principle (GA) through the skin barrier, located in the stratum corneum, and its penetration into the different compartments of the skin, epidermis and dermis. An ex vivo assessment was performed to evaluate the antioxidant effect of the ME-GA on the stratum corneum (SC) using the thiobarbituric acid-reactive species (TBARS) test. The test is based on a non invasive ex vivo methodology that evaluates lipid peroxides formed in the outermost layers of the SC from human volunteers after UV radiation to determine the effectiveness of an antioxidant. In this case, a ME-GA cosmeto-textile or ME GA formulation were applied to the skin in vivo and lipid peroxidation (LPO) in the horny layer were determined after UV irradiation. This methodology may be used as a quality control tool to determine ex vivo the percentage of LPO inhibition on human SC for a variety of antioxidants that are topically applied, in this case GA. Results show that LPO formation was inhibited in human SC when GA was applied directly or embedded in the cosmeto-textile, demonstrating the effectiveness of both applications. The percentage of LPO inhibition obtained after both topical applications was approximately 10% for the cosmeto-textile and 41% for the direct application of microspheres containing GA. This methodology could be used to determine the effectiveness of topically applied antioxidants encapsulated in cosmeto-textiles on human SC. PMID- 26848531 TI - Phenylethyl isothiocyanate reverses cisplatin resistance in biliary tract cancer cells via glutathionylation-dependent degradation of Mcl-1. AB - Biliary tract cancer (BTC) is a highly malignant cancer. BTC exhibits a low response rate to cisplatin (CDDP) treatment, and therefore, an understanding of the mechanism of CDDP resistance is urgently needed. Here, we show that BTC cells develop CDDP resistance due, in part, to upregulation of myeloid cell leukemia 1 (Mcl-1). Phenylethyl isothiocyanate (PEITC), a natural compound found in watercress, could enhance the efficacy of CDDP by degrading Mcl-1. PEITC-CDDP co treatment also increased the rate of apoptosis of cancer stem-like side population (SP) cells and inhibited xenograft tumor growth without obvious toxic effects. In vitro, PEITC decreased reduced glutathione (GSH), which resulted in decreased GSH/oxidized glutathione (GSSG) ratio and increased glutathionylation of Mcl-1, leading to rapid proteasomal degradation of Mcl-1. Furthermore, we identified Cys16 and Cys286 as Mcl-1 glutathionylation sites, and mutating them resulted in PEITC-mediated degradation resistant Mcl-1 protein. In conclusion, we demonstrate for the first time that CDDP resistance is partially associated with Mcl-1 in BTC cells and we identify a novel mechanism that PEITC can enhance CDDP induced apoptosis via glutathionylation-dependent degradation of Mcl-1. Hence, our results provide support that dietary intake of watercress may help reverse CDDP resistance in BTC patients. PMID- 26848534 TI - Access-site bleeding and radial artery occlusion in transradial primary percutaneous coronary intervention: influence of adjunctive antiplatelet therapy. AB - BACKGROUND: The aim of this study was to evaluate access-site complications in patients with ST-segment elevation myocardial infarction treated with a transradial primary percutaneous coronary intervention relative to three different P2Y12 platelet inhibitors. PATIENTS AND METHODS: We enrolled 334 consecutive patients (76.9% men, age: 59.4+/-9.1 years) treated by one of the following: clopidogrel (n=118), prasugrel (n=102), and ticagrelor (n=114). The use of the IIb/IIIa inhibitor, abciximab, was left to the operators' discretion. The time needed to achieve patent hemostasis, compression time, and local complications were analyzed. RESULTS: The baseline characteristics were similar in all three P2Y12 platelet inhibitor groups. Abciximab was used in 72 (21.6%) patients. Administration of abciximab was associated with a higher incidence of grade II and III hematomas (23.6 vs. 5.0%, P<0.0001, and 5.6 vs. 1.1%, P=0.041, respectively). Among different platelet P2Y12 receptor inhibitor groups, the incidences of hematomas grade II and III were similar in patients who did (P>=0.14) and did not (P>=0.31) receive abciximab. There were no grade IV or V hematomas in any of the groups. Patent hemostasis was achieved faster (24.5+/ 13.4 vs. 43.5+/-30.0 min, P<0.0001) and compression time was shorter (113.2+/ 53.6 vs. 217.8+/-115.5 min, P<0.0001) when abciximab was not used. Radial artery occlusion occurred in one (0.3%) patient. CONCLUSION: After transradial primary percutaneous coronary intervention, early patent hemostasis and short artery compression times were associated with a higher incidence of local hematomas. The incidence of hematomas was dependent on the use of abciximab, but unrelated to the type of P2Y12 inhibitor used. All hematomas were without clinical consequences. PMID- 26848535 TI - Dynamic changes in left ventricular function after a percutaneous coronary intervention: prevalence, predictors, and prognosis. AB - OBJECTIVES: To estimate the prevalence, identify predictors, and assess the prognostic implications of left ventricular ejection fraction (LVEF) changes after an elective percutaneous coronary intervention (PCI). METHODS: We included all consecutive patients who underwent elective PCI in our institution and were evaluated with echocardiography before and within 1 year of the procedure. Patients were grouped in terms of baseline LVEF. Hazard ratios (HRs) for all cause mortality and acute myocardial infarction were calculated for baseline LVEF groups and in terms of LVEF normalization or decline. RESULTS: A total of 974 patients were included. Patients with moderately impaired (HR 1.41, P=0.01) and poor LVEF (HR 2.44, P<0.001) had significantly worse survival in comparison with patients with good LVEF. Decline from preserved to impaired LVEF following PCI was associated with an increased 1-year risk (HR 3.48, P<0.001) and 5-year risk (HR 2.79, P<0.001) for the composite outcome of all-cause mortality and acute myocardial infarction. LVEF recovery from impaired to preserved was associated with a decreased 5-year risk for the composite outcome (HR 0.5, P<0.001). CONCLUSION: Changes in LVEF after elective PCI occur often. Both higher baseline LVEF and post-PCI LVEF normalization are associated with improved outcomes. PMID- 26848536 TI - A rapid and sensitive LC-MS/MS method for quantification of quercetin-3-O-beta-d glucopyranosyl-7-O-beta-d-gentiobioside in plasma and its application to a pharmacokinetic study. AB - A rapid and sensitive LC-MS/MS method with good accuracy and precision was developed and validated for the pharmacokinetic study of quercetin-3-O-beta-d glucopyranosyl-7-O-beta-d-gentiobioside (QGG) in Sprague-Dawley rats. Plasma samples were simply precipitated by methanol and then analyzed by LC-MS/MS. A Venusil(r) ASB C18 column (2.1 * 50 mm, i.d. 5 MUm) was used for separation, with methanol-water (50:50, v/v) as the mobile phase at a flow rate of 300 MUL/min. The optimized mass transition ion-pairs (m/z) for quantitation were 787.3/301.3 for QGG, and 725.3/293.3 for internal standard. The linear range was 7.32-1830 ng/mL with an average correlation coefficient of 0.9992, and the limit of quantification was 7.32 ng/mL. The intra- and inter-day precision and accuracy were less than +/-15%. At low, medium and high quality control concentrations, the recovery and matrix effect of the analyte and IS were in the range of 89.06 92.43 and 88.58-97.62%, respectively. The method was applied for the pharmacokinetic study of QGG in Sprague-Dawley rats. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26848537 TI - Autophagy and 3-Phosphoinositide-Dependent Kinase 1 (PDK1)-Related Kinome in Pagetic Osteoclasts. AB - In Paget's disease of bone (PDB), a major contributory factor are osteoclasts (OCs) that are larger, more numerous, resistant to apoptosis, and hyperactive. The aim of this human in vitro study was to identify kinase cascades involved in the OC phenotype and to determine their impact on downstream processes. Basal phosphorylation levels of Akt and ERK were found to be elevated in PDB OCs. Given our previous findings that 3-phosphoinositide-dependent protein kinase 1 (PDK1) associates with the crucial adaptor p62 in OCs, we hypothesized that PDK1 may play an important role in OC-related kinome regulation. The increased phosphorylation of Akt and its substrate GSK3beta observed in PDB OCs was reduced significantly upon PDK1 inhibition, as well as that of 4EBP1 and Raptor. This suggests a PDK1/Akt-dependent activation of mammalian target of rapamycin complex 1 (mTORC1) in PDB OCs. The resistance to apoptosis and the bone resorption were also overcome upon PDK1 inhibition. Studying autophagy by LC3B expression, we found a less inducible autophagy compared with control cells, which was reversed by PDK1 inhibition. In addition, PBD OCs exhibited higher LC3B-II/LC3B-I ratios and numbers of p62 and LC3B puncta per OC area, which did not further increase in the presence of lysosomal protease inhibitors, suggesting an accumulation of non degradative autophagosomes. Together these results indicate a strong potential regulatory role for PDK1 in OC stimulatory pathways (Akt, ERK) and autophagy induction (via mTORC1), which may contribute to the OC phenotype in PDB. We also identified defects in late autophagosome maturation in these cells, the mechanism of which remains to be determined. (c) 2016 American Society for Bone and Mineral Research. PMID- 26848538 TI - Integration of decoy domains derived from protein targets of pathogen effectors into plant immune receptors is widespread. AB - Plant immune receptors of the class of nucleotide-binding and leucine-rich repeat domain (NLR) proteins can contain additional domains besides canonical NB-ARC (nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4 (NB-ARC)) and leucine-rich repeat (LRR) domains. Recent research suggests that these additional domains act as integrated decoys recognizing effectors from pathogens. Proteins homologous to integrated decoys are suspected to be effector targets and involved in disease or resistance. Here, we scrutinized 31 entire plant genomes to identify putative integrated decoy domains in NLR proteins using the Interpro search. The involvement of the Zinc Finger-BED type (ZBED) protein containing a putative decoy domain, called BED, in rice (Oryza sativa) resistance was investigated by evaluating susceptibility to the blast fungus Magnaporthe oryzae in rice over-expression and knock-out mutants. This analysis showed that all plants tested had integrated various atypical protein domains into their NLR proteins (on average 3.5% of all NLR proteins). We also demonstrated that modifying the expression of the ZBED gene modified disease susceptibility. This study suggests that integration of decoy domains in NLR immune receptors is widespread and frequent in plants. The integrated decoy model is therefore a powerful concept to identify new proteins involved in disease resistance. Further in-depth examination of additional domains in NLR proteins promises to unravel many new proteins of the plant immune system. PMID- 26848540 TI - Male behaviour drives assortative reproduction during the initial stage of secondary contact. AB - Phenotypic divergence in allopatry can facilitate speciation by reducing the likelihood that individuals of different lineages hybridize during secondary contact. However, few studies have established the causes of reproductive isolation in the crucial early stages of secondary contact. Here, we establish behavioural causes of assortative reproduction between two phenotypically divergent lineages of the European wall lizard (Podarcis muralis), which have recently come into secondary contact. Parentage was highly assortative in experimental contact zones. However, despite pronounced divergence in male phenotypes, including chemical and visual sexual signals, there was no evidence that females discriminated between males of the two lineages in staged interactions or under naturalistic free-ranging conditions. Instead, assortative reproduction was driven by male mate preferences and, to a lesser extent, male male competition. The effects were more pronounced when the habitat structure promoted high lizard densities. These results emphasize that assortative reproduction can occur in the absence of female choice and that male behaviour may play an important role in limiting hybridization during the initial stages of secondary contact. PMID- 26848539 TI - Identification and functional characterization of the AGO1 ortholog in maize. AB - Eukaryotic Argonaute proteins play primary roles in miRNA and siRNA pathways that are essential for numerous developmental and biological processes. However, the functional roles of the four ZmAGO1 genes have not yet been characterized in maize (Zea mays L.). In the present study, ZmAGO1a was identified from four putative ZmAGO1 genes for further characterization. Complementation of the Arabidopsis ago1-27 mutant with ZmAGO1a indicated that constitutive overexpression of ZmAGO1a could restore the smaller rosette, serrated leaves, later flowering and maturation, lower seed set, and darker green leaves at late stages of the mutant to the wild-type phenotype. The expression profiles of ZmAGO1a under five different abiotic stresses indicated that ZmAGO1a shares expression patterns similar to those of Argonaute genes in rice, Arabidopsis, and wheat. Further, variation in ZmAGO1a alleles among diverse maize germplasm that resulted in several amino acid changes revealed genetic diversity at this locus. The present data suggest that ZmAGO1a might be an important AGO1 ortholog in maize. The results presented provide further insight into the function of ZmAGO1a. PMID- 26848542 TI - Laboratory rhesus macaque social housing and social changes: Implications for research. AB - Macaque species, specifically rhesus (Macaca mulatta), are the most common nonhuman primates (NHPs) used in biomedical research due to their suitability as a model of high priority diseases (e.g., HIV, obesity, cognitive aging), cost effective breeding and housing compared to most other NHPs, and close evolutionary relationship to humans. With this close evolutionary relationship, however, is a shared adaptation for a socially stimulating environment, without which both their welfare and suitability as a research model are compromised. While outdoor social group housing provides the best approximation of a social environment that matches the macaque behavioral biology in the wild, this is not always possible at all facilities, where animals may be housed indoors in small groups, in pairs, or alone. Further, animals may experience many housing changes in their lifetime depending on project needs, changes in social status, management needs, or health concerns. Here, we review the evidence for the physiological and health effects of social housing changes and the potential impacts on research outcomes for studies using macaques, particularly rhesus. We situate our review in the context of increasing regulatory pressure for research facilities to both house NHPs socially and mitigate trauma from social aggression. To meet these regulatory requirements and further refine the macaque model for research, significant advances must be made in our understanding and management of rhesus macaque social housing, particularly pair-housing since it is the most common social housing configuration for macaques while on research projects. Because most NHPs are adapted for sociality, a social context is likely important for improving repeatability, reproducibility, and external validity of primate biomedical research. Am. J. Primatol. 79:e22528, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26848544 TI - Fully automated muscle quality assessment by Gabor filtering of second harmonic generation images. AB - Although structural changes on the sarcomere level of skeletal muscle are known to occur due to various pathologies, rigorous studies of the reduced sarcomere quality remain scarce. This can possibly be explained by the lack of an objective tool for analyzing and comparing sarcomere images across biological conditions. Recent developments in second harmonic generation (SHG) microscopy and increasing insight into the interpretation of sarcomere SHG intensity profiles have made SHG microscopy a valuable tool to study microstructural properties of sarcomeres. Typically, sarcomere integrity is analyzed by fitting a set of manually selected, one-dimensional SHG intensity profiles with a supramolecular SHG model. To circumvent this tedious manual selection step, we developed a fully automated image analysis procedure to map the sarcomere disorder for the entire image at once. The algorithm relies on a single-frequency wavelet-based Gabor approach and includes a newly developed normalization procedure allowing for unambiguous data interpretation. The method was validated by showing the correlation between the sarcomere disorder, quantified by the M-band size obtained from manually selected profiles, and the normalized Gabor value ranging from 0 to 1 for decreasing disorder. Finally, to elucidate the applicability of our newly developed protocol, Gabor analysis was used to study the effect of experimental autoimmune encephalomyelitis on the sarcomere regularity. We believe that the technique developed in this work holds great promise for high-throughput, unbiased, and automated image analysis to study sarcomere integrity by SHG microscopy. PMID- 26848545 TI - Neuromuscular Adaptations After 2 and 4 Weeks of 80% Versus 30% 1 Repetition Maximum Resistance Training to Failure. AB - Jenkins, NDM, Housh, TJ, Buckner, SL, Bergstrom, HC, Cochrane, KC, Hill, EC, Smith, CM, Schmidt, RJ, Johnson, GO, and Cramer, JT. Neuromuscular adaptations after 2 and 4 weeks of 80% versus 30% 1 repetition maximum resistance training to failure. J Strength Cond Res 30(8): 2174-2185, 2016-The purpose of this study was to investigate the hypertrophic, strength, and neuromuscular adaptations to 2 and 4 weeks of resistance training at 80 vs. 30% 1 repetition maximum (1RM) in untrained men. Fifteen untrained men (mean +/- SD; age = 21.7 +/- 2.4 years; weight = 84.7 +/- 23.5 kg) were randomly assigned to either a high-load (n = 7) or low-load (n = 8) resistance training group and completed forearm flexion resistance training to failure 3 times per week for 4 weeks. Forearm flexor muscle thickness (MT) and echo intensity, maximal voluntary isometric (MVIC) and 1RM strength, and the electromyographic, mechanomyographic (MMG), and percent voluntary activation (%VA) responses at 10-100% of MVIC were determined at baseline, 2, and 4 weeks of training. The MT increased from baseline (2.9 +/- 0.1 cm) to week 2 (3.0 +/- 0.1 cm) and to week 4 (3.1 +/- 0.1 cm) for the 80 and 30% 1RM groups. MVIC increased from week 2 (121.5 +/- 19.1 Nm) to week 4 (138.6 +/- 22.1 Nm) and 1RM increased from baseline (16.7 +/- 1.6 kg) to weeks 2 and 4 (19.2 +/- 1.9 and 20.5 +/- 1.8 kg) in the 80% 1RM group only. The MMG amplitude at 80 and 90% MVIC decreased from baseline to week 4, and %VA increased at 20 and 30% MVIC for both groups. Resistance training to failure at 80 vs. 30% 1RM elicited similar muscle hypertrophy, but only 80% 1RM increased muscle strength. However, these disparate strength adaptations were difficult to explain with neuromuscular adaptations because they were subtle and similar for the 80 and 30% 1RM groups. PMID- 26848543 TI - Rotational imaging optical coherence tomography for full-body mouse embryonic imaging. AB - Optical coherence tomography (OCT) has been widely used to study mammalian embryonic development with the advantages of high spatial and temporal resolutions and without the need for any contrast enhancement probes. However, the limited imaging depth of traditional OCT might prohibit visualization of the full embryonic body. To overcome this limitation, we have developed a new methodology to enhance the imaging range of OCT in embryonic day (E) 9.5 and 10.5 mouse embryos using rotational imaging. Rotational imaging OCT (RI-OCT) enables full-body imaging of mouse embryos by performing multiangle imaging. A series of postprocessing procedures was performed on each cross-section image, resulting in the final composited image. The results demonstrate that RI-OCT is able to improve the visualization of internal mouse embryo structures as compared to conventional OCT. PMID- 26848547 TI - Comparison of EASYPREP((r)) and SurePath((r)) in thyroid fine-needle aspiration. AB - BACKGROUND: While fine-needle aspiration cytology (FNAC) using conventional smear has been widely accepted as the primary diagnostic tool for thyroid lesions, liquid-based preparations (LBPs) are increasingly replacing it. A new automated LBP method, EASYPREP((r)) (EP), was recently introduced and has shown relevant diagnostic efficacy in gynecologic samples. We compared the diagnostic utility of EP and SurePath((r)) (SP), a more widely established LBP method, in thyroid FNAC. METHODS: Under the ultrasonographic guidance, 253 thyroid FNAC samples were collected by sample-splitting manner. Three pathologists made cytologic diagnoses of EP and SP according to the Bethesda system independently and compared the cytomorphologic parameters. Cytohistologic correlation was performed in 30 resected cases. RESULTS: Fifteen (5.9%) and 21 (8.3%) samples were unsatisfactory in SP and EP, respectively, owing to the unequal sample-splitting. Cytologic diagnoses of SP and EP were consistent in 228 cases (90.1%), and inconsistent in remainder mostly owing to the unequal distribution of pathognomic cells. While cytomorphologic parameters were not significantly different between two methods, EP showed less three-dimensional configuration in benign lesions. Cytohistologic correlation showed no significant differences in sensitivity (100% vs. 95.5%) and specificity (100% vs. 100%) between SP and EP. Labor time for processing 48 cases was 42% shorter with EP than with SP (28 min vs. 48 min). CONCLUSIONS: The diagnostic utility of EP in thyroid FNAC was comparable to that of SP. EP allowed better visibility owing to better fragmentation of follicular clusters. The automated system of EP has the advantages of a shorter labor time for batch processing. Diagn. Cytopathol. 2016;44:283-290. (c) 2016 Wiley Periodicals, Inc. PMID- 26848548 TI - Crosslinked dendronized polyols as a general approach to brighter and more stable fluorophores. AB - Fluorescent, aqueous-soluble, crosslinked dendronized polyols (CDPs) are obtained through a sequential process involving ring-opening metathesis polymerization (ROMP), intra-chain ring-closing metathesis (RCM), and hydrolysis. This general strategy improves the quantum yields (QYs), brightness, and photostability of five common fluorophores whose emission wavelengths cover 150 nm. Additionally, the availability of the polymeric fluorophore to the cytosomes opens the door to applications in bioimaging and intracellular delivery. PMID- 26848549 TI - Functional analysis of alternative transcripts of the soybean Rj2 gene that restricts nodulation with specific rhizobial strains. AB - The Rj2 gene is a TIR-NBS-LRR-type resistance gene in soybean (Glycine max) that restricts root nodule symbiosis with a group of Bradyrhizobium japonicum strains including USDA122. Rj2 generates two distinct transcript variants in its expression profile through alternative splicing. Alternative splicing of Rj2 is caused by the retention of the 86-bp intron 4. Inclusion of intron 4 in mature mRNA introduces an in-frame stop codon; as such, the alternative transcript is predicted to encode a truncated protein consisting of the entire portion of the TIR, NBS and LRR domains but missing the C-terminal domain of the full-length Rj2 protein encoded by the regular transcript. Since alternative splicing has been shown to be essential for full activity of several plant R genes, we attempted to test whether the alternative splicing is required for Rj2-mediated nodulation restriction. Here we demonstrated that the Rj2-mediated nodulation restriction does not require the combined presence of the regular and alternative transcripts, and the expression of the regular transcript alone is sufficient to confer nodulation restriction. PMID- 26848550 TI - Functional Immune Anatomy of the Liver-As an Allograft. AB - The liver is an immunoregulatory organ in which a tolerogenic microenvironment mitigates the relative "strength" of local immune responses. Paradoxically, necro inflammatory diseases create the need for most liver transplants. Treatment of hepatitis B virus, hepatitis C virus, and acute T cell-mediated rejection have redirected focus on long-term allograft structural integrity. Understanding of insults should enable decades of morbidity-free survival after liver replacement because of these tolerogenic properties. Studies of long-term survivors show low grade chronic inflammatory, fibrotic, and microvascular lesions, likely related to some combination of environment insults (i.e. abnormal physiology), donor specific antibodies, and T cell-mediated immunity. The resultant conundrum is familiar in transplantation: adequate immunosuppression produces chronic toxicities, while lightened immunosuppression leads to sensitization, immunological injury, and structural deterioration. The "balance" is more favorable for liver than other solid organ allografts. This occurs because of unique hepatic immune physiology and provides unintended benefits for allografts by modulating various afferent and efferent limbs of allogenic immune responses. This review is intended to provide a better understanding of liver immune microanatomy and physiology and thereby (a) the potential structural consequences of low-level, including allo-antibody-mediated injury; and (b) how liver allografts modulate immune reactions. Special attention is given to the microvasculature and hepatic mononuclear phagocytic system. PMID- 26848551 TI - Impulsivity and gambling: A complex clinical association across three measures. AB - BACKGROUND AND OBJECTIVES: Gambling disorder (GD) is often characterized as an impulsive condition, but results to date have varied substantially by the measure used to assess impulsivity and the modality of the assessment. The purpose of this analysis was to assess the clinical associations between three measures of impulsivity (Eysenck impulsiveness questionnaire [EIQ], Barratt impulsiveness scale [BIS], and stop-signal task [SST]) and GD symptom severity. METHODS: One hundred and fifty-four participants with a current GD diagnosis were assessed on at least one of the three measures of impulsivity and additional clinical measures of gambling severity. Groups within each domain of the measures were divided using a mean split to compare high and low impulsivity (HI and LI) across clinical and demographic variables. RESULTS: Of the included domains, the motor impulsivity domain of the BIS showed multiple clinical differences between the HI and LI groups. The attentional impulsivity domain of the BIS showed limited clinical associations. Surprisingly, HI and LI groups from the SST and EIQ domains did not show any differences in symptom severity. DISCUSSION AND CONCLUSIONS: These findings emphasize the complex nature of impulsivity, particularly as it relates to GD. With disparate results between different measures, it will be important to clarify the specific features assessed by each measure, and their optimal use clinically. SCIENTIFIC SIGNIFICANCE: This analysis suggests that the motor impulsivity feature of the BIS shows the strongest clinical utility for predicting gambling severity. It also emphasizes the importance of sub-typing impulsivity, rather than considering it a single neurocognitive feature. PMID- 26848553 TI - Perfluorocarbon-Loaded Hollow Bi2Se3 Nanoparticles for Timely Supply of Oxygen under Near-Infrared Light to Enhance the Radiotherapy of Cancer. AB - Hollow Bi2 Se3 nanoparticles prepared by a cation exchange method are loaded with perfluorocarbon as an oxygen carrier. With these nanoparticles, a promising concept is demonstrated to enhance radiotherapy by not only using their X-ray absorbing ability to locally concentrate radiation energy in the tumor, but also employing near-infrared light to trigger burst release of oxygen from the nanoparticles to overcome hypoxia-associated radio-resistance. PMID- 26848554 TI - Reimagining care for adolescent and young adult cancer programs: Moving with the times. AB - Literature regarding the development of adolescent and young adult (AYA) cancer programs has been dominantly informed by pediatric centers and practitioners. However, the majority of young adults are seen and treated at adult cancer centers, in which cancer volumes afford the development of innovative supportive care services. Although the supportive care services in adult cancer centers are helpful to AYAs, some of the most prominent and distinct issues faced by AYAs are not adequately addressed through these services alone. This article describes how the AYA Program at Princess Margaret Cancer Centre has collaborated with existing supportive care services in addition to supplying its own unique services to meet the comprehensive needs of AYAs in the domains of: symptom management (sexuality and fatigue), behavior modification (return to work and exercise), and health services (advanced cancer and survivorship). These collaborations are augmented by patient education interventions and timely referrals. The objective of this article was to assist other centers in expanding existing services to address the needs of AYA patients with cancer. PMID- 26848556 TI - Clinical Resting-state fMRI in the Preoperative Setting: Are We Ready for Prime Time? AB - The purpose of this manuscript is to provide an introduction to resting-state functional magnetic resonance imaging (RS-fMRI) and to review the current application of this new and powerful technique in the preoperative setting using our institute's extensive experience. RS-fMRI has provided important insights into brain physiology and is an increasingly important tool in the clinical setting. As opposed to task-based functional MRI wherein the subject performs a task while being scanned, RS-fMRI evaluates low-frequency fluctuations in the blood oxygen level dependent (BOLD) signal while the subject is at rest. Multiple resting state networks (RSNs) have been identified, including the somatosensory, language, and visual networks, which are of primary importance for presurgical planning. Over the past 4 years, we have performed over 300 RS-fMRI examinations in the clinical setting and these have been used to localize eloquent somatosensory and language cortices before brain tumor resection. RS-fMRI is particularly useful in this setting for patients who are unable to cooperate with the task-based paradigm, such as young children or those who are sedated, paretic, or aphasic.Although RS-fMRI is still investigational, our experience indicates that this method is ready for clinical application in the presurgical setting. PMID- 26848555 TI - Language Mapping Using fMRI and Direct Cortical Stimulation for Brain Tumor Surgery: The Good, the Bad, and the Questionable. AB - Language functional magnetic resonance imaging for neurosurgical planning is a useful but nuanced technique. Consideration of primary and secondary language anatomy, task selection, and data analysis choices all impact interpretation. In the following chapter, we consider practical considerations and nuances alike for language functional magnetic resonance imaging in the support of and comparison with the neurosurgical gold standard, direct cortical stimulation. Pitfalls and limitations are discussed. PMID- 26848552 TI - Transport physics and biorheology in the setting of hemostasis and thrombosis. AB - The biophysics of blood flow can dictate the function of molecules and cells in the vasculature with consequent effects on hemostasis, thrombosis, embolism, and fibrinolysis. Flow and transport dynamics are distinct for (i) hemostasis vs. thrombosis and (ii) venous vs. arterial episodes. Intraclot transport changes dramatically the moment hemostasis is achieved or the moment a thrombus becomes fully occlusive. With platelet concentrations that are 50- to 200-fold greater than platelet-rich plasma, clots formed under flow have a different composition and structure compared with blood clotted statically in a tube. The platelet rich, core/shell architecture is a prominent feature of self-limiting hemostatic clots formed under flow. Importantly, a critical threshold concentration of surface tissue factor is required for fibrin generation under flow. Once initiated by wall-derived tissue factor, thrombin generation and its spatial propagation within a clot can be modulated by gamma'-fibrinogen incorporated into fibrin, engageability of activated factor (FIXa)/activated FVIIIa tenase within the clot, platelet-derived polyphosphate, transclot permeation, and reduction of porosity via platelet retraction. Fibrin imparts tremendous strength to a thrombus to resist embolism up to wall shear stresses of 2400 dyne cm(-2) . Extreme flows, as found in severe vessel stenosis or in mechanical assist devices, can cause von Willebrand factor self-association into massive fibers along with shear-induced platelet activation. Pathological von Willebrand factor fibers are A Disintegrin And Metalloprotease with ThromboSpondin-1 domain 13 resistant but are a substrate for fibrin generation due to FXIIa capture. Recently, microfluidic technologies have enhanced the ability to interrogate blood in the context of stenotic flows, acquired von Willebrand disease, hemophilia, traumatic bleeding, and drug action. PMID- 26848557 TI - Presurgical Mapping of the Language Network Using Resting-state Functional Connectivity. AB - Resting-state functional magnetic resonance imaging (resting-state fMRI) is a tool for investigating the functional networks that arise during the resting state of the brain. Recent advances of the resting-state fMRI analysis suggest its feasibility for evaluating language function. The most common clinical application is for presurgical mapping of cortex for a brain tumor or for resective epilespy surgery. In this article, we review the techniques and presurgical applications of resting-state fMRI analysis for language evaluation, and discuss the use in the clinical setting, focusing on planning for neurosurgery. PMID- 26848558 TI - Cortical Plasticity in the Setting of Brain Tumors. AB - Cortical reorganization of function due to the growth of an adjacent brain tumor has clearly been demonstrated in a number of surgically proven cases. Such cases demonstrate the unmistakable implications for the neurosurgical treatment of brain tumors, as the cortical function may not reside where one may initially suspect based solely on the anatomical magnetic resonance imaging (MRI). Consequently, preoperative localization of eloquent areas adjacent to a brain tumor is necessary, as this may demonstrate unexpected organization, which may affect the neurosurgical approach to the lesion. However, in interpreting functional MRI studies, the interpreting physician must be cognizant of artifacts, which may limit the accuracy of functional MRI in the setting of brain tumors. PMID- 26848560 TI - Predictors of Medical Management in Patients Undergoing Elective Cardiac Catheterization for Chronic Ischemic Heart Disease. AB - BACKGROUND: Compared with medical therapy, percutaneous coronary intervention (PCI) does not reduce mortality or myocardial infarction in patients with stable angina. Therefore, PCI should be guided by refractory anginal symptoms and not just lesion characteristics. HYPOTHESIS: We hypothesized that angiographic lesion characteristics and stress test results would have a greater role in the decision to proceed with PCI than would symptom severity. METHODS: We performed a retrospective cohort study of patients undergoing elective cardiac catheterization and possible PCI at an academic medical center. Anginal symptoms, optimal medical therapy, antianginal therapy, stress test results, and angiographic lesions (including American College of Cardiology/American Heart Association [ACC/AHA] lesion type) were analyzed. Logistic regression was used to determine predictors of medical management among patients not referred for coronary artery bypass surgery. RESULTS: Of the 207 patients with obstructive lesions amenable to PCI, 163 underwent PCI and 44 were referred to medical therapy. In the multivariable logistic model, the following variables were associated with medical management: advancing age (odds ratio [OR] per 1 year: 0.94, 95% confidence interval [CI]: 0.91-0.98), chronic kidney disease (OR: 0.23, 95% CI: 0.06-0.95), distal location (OR: 0.21, 95% CI: 0.09-0.48), and ACC/AHA type C lesion (OR: 0.08, 95% CI: 0.03-0.22). There was no association with sex, race, symptoms, optimal medical therapy, maximal antianginal therapy, referral status, or type of interventional cardiologist (academic vs private practice). CONCLUSIONS: For patients undergoing cardiac catheterization for stable angina, the decision to proceed to PCI vs medical management appears to depend largely on patient and angiographic characteristics, but not on symptoms or ischemia. Distal and high-risk lesions (ACC/AHA type C) are more often referred for medical therapy. PMID- 26848561 TI - Minocycline added to subcutaneous interferon beta-1a in multiple sclerosis: randomized RECYCLINE study. AB - BACKGROUND AND PURPOSE: Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) beta-1a therapy. METHODS: This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (+/-1 month) of starting sc IFN beta-1a 44 MUg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN beta-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed. RESULTS: One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo. CONCLUSION: Minocycline showed no statistically significant beneficial effect when added to sc IFN beta-1a therapy. PMID- 26848559 TI - Hyperpolarization MRI: Preclinical Models and Potential Applications in Neuroradiology. AB - Hyperpolarization is a novel technology that can dramatically increase signal to noise in magnetic resonance. The method is being applied to small injectable endogenous molecules, which can be used to monitor transient in vivo metabolic events, in real time. The emergence of hyperpolarized C-labeled probes, specifically C pyruvate, has enabled monitoring of core cellular metabolic events. Neuro-oncological applications have been demonstrated in preclinical models. Many more applications of this technology are envisioned, with transformative potential in magnetic resonance imaging. PMID- 26848562 TI - Atp13a2 Deficiency Aggravates Astrocyte-Mediated Neuroinflammation via NLRP3 Inflammasome Activation. AB - AIM: Atp13a2 (Park9) gene encodes a transmembrane lysosomal P5-type ATPase (ATP13A2), and its missense or truncation mutations leads to lysosomal dysfunction and consequently results in neuronal death in the pathogenesis of Parkinson's disease (PD). Nevertheless, the roles of ATP13A2 in the biological features of astrocytes, especially in the regulation of PD-related neuroinflammation, have not been investigated. METHODS: We cultured primary neurons and astrocytes from mouse midbrain to investigate the mechanisms for astrocyte ATP13A2-regulated lysosomal function and neuroinflammation following 1 methyl-4-phenylpyridinium (MPP(+) ) treatment. RESULTS: We found that astrocytes expressed considerable levels of ATP13A2 and deficiency of ATP13A2 in astrocyte induced intense inflammation, which exacerbated dopaminergic neuron damage after exposure to MPP(+) . Notably, lack of ATP13A2 increased lysosomal membrane permeabilization and cathepsin B release, which in turn exacerbated activation of nod-like receptor protein 3 (NLRP3) inflammasome to produce excess IL-1beta from astrocytes. Furthermore, overexpression of ATP13A2 reversed MPP(+) -induced cathepsin B release and NLRP3 inflammasome activation in astrocytes. CONCLUSIONS: Our results have revealed a novel role of ATP13A2 in modulating astrocyte mediated neuroinflammation via NLRP3 inflammasome activation, thus bringing to light of a direct link between astrocyte lysosome and neuroinflammation in the pathological model of PD. PMID- 26848563 TI - Complications and Risk after Mandibular Reconstruction with Fibular Free Flaps in Patients with Oral Squamous Cell Carcinoma: A Retrospective Cohort Study. AB - Background We retrospectively analyzed the incidence and types of postoperative complications after mandibular continuity reconstructions with fibular free flaps (FFF) in patients with oral squamous cell carcinoma (OSCC) and identified potential risk factors for postoperative complications. Methods Data were retrieved from the medical records in the Department of Oral and Maxillofacial Surgery/Oral Pathology, VU University Medical Center/Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands from April 1995 to September 2013, and were statistically analyzed. Results In this study, 85 patients were included in whom 86 FFFs were used for mandibular reconstruction. Thirty-seven patients (43%) developed >= 1 surgical complication and 9 patients (10.5%) developed >= 1 systemic complication. Three patients (3.5%) developed total flap failure and six patients (7.0%) developed partial flap failure. Surgical complications were correlated with tobacco use, partial glossectomy, type of mandibular defect, and anatomic staging. Systemic complications were associated with age > 60 years and Charlson comorbidity index > 2. Hospitalization > 30 days was associated with type of mandibular defect. Conclusions The use of the FFF for reconstructing mandibular continuity defects in OSCC patients may be associated with postoperative complications. Patients with coexisting medical conditions and anterior mandibular defects have an increased risk for developing complications. Patients who undergo segmental mandibular resection including a partial glossectomy could have a reduced risk for complications. PMID- 26848564 TI - Role of Free Iliac Crest Flap in Foot and Ankle Reconstruction. AB - Background Reconstruction of extensive bone and compound defects in the foot and ankle is challenging. This cross-sectional study aimed to assess the outcomes of free iliac crest flap in foot and ankle reconstruction. Methods We retrospectively reviewed patient records and identified 13 cases with 1 osseous and 12 composite free iliac crest grafts for compound fracture (n = 3) or sequelae (n = 10) in the foot and ankle. We applied the visual analogue scale foot and ankle, the Oswestry disability index, and the 15D health-related quality of life (HRQoL) instruments. Results The average follow-up period was 3.9 years (range, 1.3-8.0 years). Four patients underwent early reoperations; venous and arterial reanastomosis (n = 1), minor wound revision (n = 2), or flap reconstruction due to partial necrosis of the skin island (n = 1). The median time to bone union was 23 months (range, 7-46 months). One permanent pseudoarthrosis occurred. One patient underwent late below-knee amputation due to chronic pain and functional impairment. One patient required flap reconstruction due to a late donor-site defect. Seven patients completed the questionnaires on an average of 14.7 years postoperatively (range, 2.0-26.9 years). Noted impairment of the donor site and of the reconstructed limb ranged from none to significant. Five (out of seven) patients had a HRQoL comparable to that of an age-standardized general population. Conclusions The free iliac crest flap is a feasible option for extensive compound fractures and bone-healing complications in the foot and ankle. It can also be used to achieve ankle arthrodesis when other techniques have failed and in patients at high risk for amputation. PMID- 26848565 TI - A Time Course Study of Different Methods of Extraneural Scar Induction in a Rat Model. AB - Background Extraneural scar formation is a challenging problem in nerve repair. Rodent models of scar induction, with their high regenerative capacity, suffer from lack of comparable similarities with human cases. In this study, we attempted to find a reliable and reproducible method of extraneural scarring with a significant impact on the peripheral nerve function. Methods A total of 60 rats were divided into three scar induction groups: abrasion (with a small piece of compressed steel wool), mincing (with extracorporeal mincing of adductor muscle and a 5-mm wide strip of the anterior border of the biceps femoris), and electrocoagulation (with a bipolar coagulator). Extraneural scarring was evaluated macroscopically and histologically during 8 weeks. The tibial functional index was used for behavioral analysis. Results Among three different physical methods of scar induction that were applied, electrocoagulation had the most functional impairment (p < 0.001, two-way analysis of variance); whereas mincing produced the most adhesive and intensive scar, morphologically (p < 0.001). Conclusion We conclude that: (1) the impact of the extraneural scar on the nerve is morphologically and functionally different, based on the method of scarring; (2) to achieve a scar model comparable to the human situation, a method in which the involved nerve is functionally impaired, is preferred over the ones that merely produce a bulky scar. PMID- 26848566 TI - Microsurgical Urethroplasty for Complex Bulbar Urethral Strictures Using the Radial Forearm Free Flap Prelaminated with Buccal Mucosa. AB - Background Complex bulbar urethral strictures are a heterogeneous group, including those secondary to radiotherapy, failed previous open urethroplasty, and total bulbar necrosis following pelvic trauma. Traditional urethroplasty techniques in this group are unpredictable. We describe a novel technique of a buccal mucosa-prelaminated radial forearm free flap urethroplasty, which seeks to improve the quality of life for this group of patients. Methods Known, reliable techniques from two surgical specialties were combined to create a novel surgical solution, consisting of a radial forearm free flap prelaminated with buccal mucosa. Prospective data were collected on patient and stricture characteristics, complications, and results, including voiding flow rates, urethrography, and cystourethroscopy. Success was defined as the ability to void per urethra. The procedure was performed in four patients, previously considered unreconstructable and who were suprapubic catheter dependent. Results Microsurgical transfer was successful in all four cases. All patients were voiding per urethra and remained catheter free at a minimum of 12-month follow-up. There was no significant donor morbidity and all patients were able to return to their usual occupation. Mean voiding flow rates were 17.3 mL/s. Flexible cystoscopy revealed well vascularized, patent neomucosa. Conclusions We demonstrate proof of concept for a novel technique of microsurgical urethroplasty. We believe this technique may have widespread application in the treatment of radiation-induced and other complex urethral strictures where traditional urethroplasty has limited success. PMID- 26848567 TI - Expanding the Utilization of the Osteocutaneous Radial Forearm Free Flap beyond Mandibular Reconstruction. AB - Background The osteocutaneous radial forearm free flap (OCRFFF) for mandibular reconstruction has been well described. Despite this flap's utility in the repair of such defects, the indications for the OCRFFF have continued to expand in recent years. The advantages of the OCRFFF allow for a high degree of versatility in the reconstruction of the various anatomical and aesthetic units of the head and neck. In this review, the authors aim to explore the successful utilization of the OCRFFF beyond the reconstruction of composite mandibular defects. Methods A retrospective chart review was performed. All subjects who underwent OCRFFF reconstruction at a tertiary academic center between January 2004 and December 2014 were identified. A total of six patients undergoing this procedure for indications other than composite mandibular defects of the head and neck were included. Results A total of six patients underwent OCRFFF reconstruction for correction of nonmandibular defects. Flap success was experienced in six of six cases (100%). Indications included midface maxillary reconstruction (N = 2), orbit reconstruction (N = 1), frontal sinus and forehead reconstruction (N = 2), and subglottic stenosis reconstruction (N = 1). There were no immediate perioperative complications. On long-term follow-up, one subject developed a nasocutaneous fistula following radiation and eventually required maxillary hardware removal. Conclusion As a result of its growing role and versatility, the OCRFFF should be incorporated as a multipurpose tool in the armamentarium of reconstructive microvascular surgeons in the repair of composite head and neck defects beyond the mandible. PMID- 26848568 TI - Vikodak--A Modular Framework for Inferring Functional Potential of Microbial Communities from 16S Metagenomic Datasets. AB - BACKGROUND: The overall metabolic/functional potential of any given environmental niche is a function of the sum total of genes/proteins/enzymes that are encoded and expressed by various interacting microbes residing in that niche. Consequently, prior (collated) information pertaining to genes, enzymes encoded by the resident microbes can aid in indirectly (re)constructing/ inferring the metabolic/ functional potential of a given microbial community (given its taxonomic abundance profile). In this study, we present Vikodak--a multi-modular package that is based on the above assumption and automates inferring and/ or comparing the functional characteristics of an environment using taxonomic abundance generated from one or more environmental sample datasets. With the underlying assumptions of co-metabolism and independent contributions of different microbes in a community, a concerted effort has been made to accommodate microbial co-existence patterns in various modules incorporated in Vikodak. RESULTS: Validation experiments on over 1400 metagenomic samples have confirmed the utility of Vikodak in (a) deciphering enzyme abundance profiles of any KEGG metabolic pathway, (b) functional resolution of distinct metagenomic environments, (c) inferring patterns of functional interaction between resident microbes, and (d) automating statistical comparison of functional features of studied microbiomes. Novel features incorporated in Vikodak also facilitate automatic removal of false positives and spurious functional predictions. CONCLUSIONS: With novel provisions for comprehensive functional analysis, inclusion of microbial co-existence pattern based algorithms, automated inter environment comparisons; in-depth analysis of individual metabolic pathways and greater flexibilities at the user end, Vikodak is expected to be an important value addition to the family of existing tools for 16S based function prediction. AVAILABILITY AND IMPLEMENTATION: A web implementation of Vikodak can be publicly accessed at: http://metagenomics.atc.tcs.com/vikodak. This web service is freely available for all categories of users (academic as well as commercial). PMID- 26848569 TI - Sleep Disturbances at 3 Months after Cerebral Infarction. AB - BACKGROUND: Post-stroke sleep disturbances (PSSD) are common and associated with various adverse outcomes. However, PSSD in the sub-acute stages of stroke have been scarcely studied. We aimed to evaluate the characteristics of and the factors related to PSSD in stroke patients 3 months post stroke. METHODS: A total of 199 patients were evaluated for PSSD at 3 months after stroke. The qualities of nighttime sleep and excessive daytime sleepiness (EDS) were assessed using the Verran Snyder-Halpern sleep scale and Epworth Sleepiness Scale, respectively. Presence of motor dysfunction and post-stroke pain, post-stroke depression, fatigue and social support were evaluated. RESULTS: Eighty-eight patients (44.2%) had poor quality of nighttime sleep. Twenty-eight patients (14.4%) reported EDS. Poor quality of nighttime sleep was independently associated with depression (p = 0.044) and EDS (p = 0.041) whereas fatigue (p < 0.001) and poor nighttime sleep (p = 0.045) were independently associated with EDS. Post-stroke pain and social support showed no association with PSSD. CONCLUSIONS: We found that the occurrence of PSSD 3 months after stroke is common. Although causality remained to be determined, depression and nighttime sleep disturbances were related, whereas fatigue and nighttime sleep disturbances were related to EDS. PMID- 26848570 TI - Effect of Omega-3 and Vitamins E + C Supplements on the Concentration of Serum B Vitamins and Plasma Redox Aminothiol Antioxidant Status in Elderly Men after Strength Training for Three Months. AB - BACKGROUND: Data on redox plasma aminothiol status in individuals on strength training are very limited. Therefore, we studied the effect of omega-3 and vitamins E + C supplementation on the concentration of B-vitamins and redox aminothiol status in elderly men after strength training for 3 months. METHODS: Healthy men, age 60 +/- 6 (mean +/- SD) were randomly divided into 3 groups: group I received placebo (n = 17), group II consumed omega-3 (700 mg, n = 17), and group III consumed vitamins E + C (235 mg +1 g, n = 16) daily for 3 months. All participants completed a strength training program for the same period. RESULTS: The concentration of serum vitamin B12 decreased and the concentration of serum folate increased in group I after the intervention (p = 0.01, p = 0.009). The concentration of plasma 5-pyridoxal phosphate decreased in groups II and III (p = 0.03 and p = 0.01), whereas the concentration of serum uric acid decreased only in group II (p = 0.02). We detected an increase in the concentration of reduced form of aminothiols in all groups (p < 0.001). The red/ox plasma aminothiol status was significantly changed in all groups after the intervention (p < 0.05). CONCLUSION: Omega-3 and vitamins E + C supplementation affect the concentrations of serum B-vitamins and redox plasma aminothiol status in healthy elderly men on strength training. PMID- 26848571 TI - Fusing Data Mining, Machine Learning and Traditional Statistics to Detect Biomarkers Associated with Depression. AB - BACKGROUND: Atheoretical large-scale data mining techniques using machine learning algorithms have promise in the analysis of large epidemiological datasets. This study illustrates the use of a hybrid methodology for variable selection that took account of missing data and complex survey design to identify key biomarkers associated with depression from a large epidemiological study. METHODS: The study used a three-step methodology amalgamating multiple imputation, a machine learning boosted regression algorithm and logistic regression, to identify key biomarkers associated with depression in the National Health and Nutrition Examination Study (2009-2010). Depression was measured using the Patient Health Questionnaire-9 and 67 biomarkers were analysed. Covariates in this study included gender, age, race, smoking, food security, Poverty Income Ratio, Body Mass Index, physical activity, alcohol use, medical conditions and medications. The final imputed weighted multiple logistic regression model included possible confounders and moderators. RESULTS: After the creation of 20 imputation data sets from multiple chained regression sequences, machine learning boosted regression initially identified 21 biomarkers associated with depression. Using traditional logistic regression methods, including controlling for possible confounders and moderators, a final set of three biomarkers were selected. The final three biomarkers from the novel hybrid variable selection methodology were red cell distribution width (OR 1.15; 95% CI 1.01, 1.30), serum glucose (OR 1.01; 95% CI 1.00, 1.01) and total bilirubin (OR 0.12; 95% CI 0.05, 0.28). Significant interactions were found between total bilirubin with Mexican American/Hispanic group (p = 0.016), and current smokers (p<0.001). CONCLUSION: The systematic use of a hybrid methodology for variable selection, fusing data mining techniques using a machine learning algorithm with traditional statistical modelling, accounted for missing data and complex survey sampling methodology and was demonstrated to be a useful tool for detecting three biomarkers associated with depression for future hypothesis generation: red cell distribution width, serum glucose and total bilirubin. PMID- 26848574 TI - Differences in Investigator-Initiated Trials between Japan and Other Countries: Analyses of Clinical Trials Sponsored by Academia and Government in the ClinicalTrials.gov Registry and in the Three Japanese Registries. AB - BACKGROUND: Following the amendment of the Pharmaceutical Affairs Law in Japan in 2003 researchers were permitted to begin investigator-initiated trials (IITs). In subsequent years, however, the number of IITs remained low. In other countries in Asia as well as in Europe, North America, and South Africa, the number of IITs has increased over the past decade. The differences in the characteristics of IITs between Japan and other countries are unknown. Some studies have analyzed the characteristics of all clinical trials according to registry databases, but there has been less research focusing on IITs. AIMS: The purpose of this study is to analyze the characteristics of IITs in the ClinicalTrials.gov registry and in the three Japanese registries, to identify differences in IITs between Japan and other countries. METHODS: Using Thomson Reuters PharmaTM, trials sponsored by academia and government as IITs in 2010 and registered in ClinicalTrials.gov were identified. IITs from 2004 to 2012 in Japan were identified in the three Japanese registries: the University Hospital Medical Information Network Clinical Trials Registry, the Japan Pharmaceutical Information Center Clinical Trials Information, and the Japan Medical Association Center for Clinical Trials, Clinical Trials Registry. Characterization was made of the trial purposes, phases, participants, masking, arms, design, controls, and other data. RESULTS: New and revised IITs registered in ClinicalTrials.gov during 2010 averaged about 40% of all sponsor-identified trials. IITs were nearly all early-phase studies with small numbers of participants. A total of 56 Japanese IITs were found over a period of 8 years, and these were also almost nearly all early-phase studies with small numbers of participants. CONCLUSION: There appear to be no great differences between Japan and other countries in terms of characteristics of IITs. These results should prompt a new review of the IIT environment in Japan. PMID- 26848573 TI - Weakened Resilience in Parenting Self-Efficacy in Pregnant Women Who Were Abused in Childhood: An Experimental Test. AB - This study tested experimentally whether the combination of a history of childhood abuse and confrontation with difficult infant temperament is associated with negative changes in parenting self-efficacy. First-time pregnant women (N = 243) participated in the Adult Attachment Interview, which was used to assess the occurrence of abuse by parents in childhood and unresolved representations, and completed a task asking them to respond to infant cries. Sixty of the 243 participants (25%) experienced childhood abuse, mostly physical or sexual. The task simulated infant temperamental difficulty by manipulating soothing success in order to reflect an easy-to-soothe (80% soothing success) and a difficult-to soothe infant (20% soothing success). Both after baseline and after each of the two stimulus series women assessed their parenting self-efficacy. Women who reported childhood abuse did not differ from women who reported no childhood abuse in parenting self-efficacy at baseline or in response to the easy-to-soothe infant (relative to baseline), but decreased more in parenting self-efficacy following the difficult-to-soothe infant. Effects did not vary according to resolution of trauma. These findings suggest that in response to infant temperamental difficulty, women who experienced childhood abuse may more easily lose confidence in their parenting abilities, which underlines the importance of preparing at-risk women for the possible challenges that come along with parenthood. PMID- 26848572 TI - Visfatin Destabilizes Atherosclerotic Plaques in Apolipoprotein E-Deficient Mice. AB - OBJECTIVES: Although there is evidence that visfatin is associated with atherogenesis, the effect of visfatin on plaque stability has not yet been explored. METHODS: In vivo, vulnerable plaques were established by carotid collar placement in apolipoprotein E-deficient (ApoE-/-) mice, and lentivirus expressing visfatin (lenti-visfatin) was locally infused in the carotid artery. The lipid, macrophage, smooth muscle cell (SMC) and collagen levels were evaluated, and the vulnerability index was calculated. In vitro, RAW264.7 cells were stimulated with visfatin, and the MMPs expressions were assessed by western blot and immunofluorescence. And the mechanism that involved in visfatin-induced MMP-8 production was investigated. RESULTS: Transfection with lenti-visfatin significantly promoted the expression of visfatin which mainly expressed in macrophages in the plaque. Lenti-visfatin transfection significantly promoted the accumulation of lipids and macrophages, modulated the phenotypes of smooth muscle cells and decreased the collagen levels in the plaques, which significantly decreased the plaque stability. Simultaneously, transfection with lenti-visfatin significantly up-regulated the expression of MMP-8 in vivo, as well as MMP-1, MMP 2 and MMP-9. Recombinant visfatin dose- and time-dependently up-regulated the in vitro expression of MMP-8 in macrophages. Visfatin promoted the translocation of NF-kappaB, and inhibition of NF-kappaB significantly reduced visfatin-induced MMP 8 production. CONCLUSIONS: Visfatin increased MMP-8 expression, promoted collagen degradation and increased the plaques vulnerability index. PMID- 26848575 TI - Alternate Directed Anthropogenic Shifts in Genotype Result in Different Ecological Outcomes in Coho Salmon Oncorhynchus kisutch Fry. AB - Domesticated and growth hormone (GH) transgenic salmon provide an interesting model to compare effects of selected versus engineered phenotypic change on relative fitness in an ecological context. Phenotype in domestication is altered via polygenic selection of traits over multiple generations, whereas in transgenesis is altered by a single locus in one generation. These established and emerging technologies both result in elevated growth rates in culture, and are associated with similar secondary effects such as increased foraging, decreased predator avoidance, and similar endocrine and gene expression profiles. As such, there is concern regarding ecological consequences should fish that have been genetically altered escape to natural ecosystems. To determine if the type of genetic change influences fitness components associated with ecological success outside of the culture environments they were produced for, we examined growth and survival of domesticated, transgenic, and wild-type coho salmon fry under different environmental conditions. In simple conditions (i.e. culture) with unlimited food, transgenic fish had the greatest growth, while in naturalized stream tanks (limited natural food, with or without predators) domesticated fish had greatest growth and survival of the three fish groups. As such, the largest growth in culture conditions may not translate to the greatest ecological effects in natural conditions, and shifts in phenotype over multiple rather than one loci may result in greater success in a wider range of conditions. These differences may arise from very different historical opportunities of transgenic and domesticated strains to select for multiple growth pathways or counter-select against negative secondary changes arising from elevated capacity for growth, with domesticated fish potentially obtaining or retaining adaptive responses to multiple environmental conditions not yet acquired in recently generated transgenic strains. PMID- 26848576 TI - Mapping of Ppd-B1, a Major Candidate Gene for Late Heading on Wild Emmer Chromosome Arm 2BS and Assessment of Its Interactions with Early Heading QTLs on 3AL. AB - Wheat heading date is an important agronomic trait determining maturation time and yield. A set of common wheat (Triticum aestivum var. Chinese Spring; CS)-wild emmer (T. turgidum L. subsp. dicoccoides (TDIC)) chromosome arm substitution lines (CASLs) was used to identify and allocate QTLs conferring late or early spike emergence by examining heading date. Genetic loci accelerating heading were found on TDIC chromosome arms 3AL and 7BS, while loci delaying heading were located on 4AL and 2BS. To map QTLs conferring late heading on 2BS, F2 populations derived from two cross combinations of CASL2BS * CS and CASL3AL * CASL2BS were developed and each planted at two times, constituting four F2 mapping populations. Heading date varied continuously among individuals of these four populations, suggesting quantitative characteristics. A genetic map of 2BS, consisting of 23 SSR and one single-stranded conformation polymorphism (SSCP) marker(s), was constructed using these F2 populations. This map spanned a genetic length of 53.2 cM with average marker density of 2.3 cM. The photoperiod sensitivity gene Ppd-B1 was mapped to chromosome arm 2BS as a SSCP molecular marker, and was validated as tightly linked to a major QTL governing late heading of CASL2BS in all mapping populations. A significant dominance by additive effect of Ppd-B1 with the LUX gene located on 3AL was also detected. CS had more copies of Ppd-B1 than CASL2BS, implying that increased copy number could elevate the expression of Ppd-1 in CS, also increasing expression of LUX and FT genes and causing CS to have an earlier heading date than CASL2BS in long days. PMID- 26848577 TI - Comparison of E,E-Farnesol Secretion and the Clinical Characteristics of Candida albicans Bloodstream Isolates from Different Multilocus Sequence Typing Clades. AB - Using multilocus sequence typing (MLST), Candida albicans can be subdivided into 18 different clades. Farnesol, a quorum-sensing molecule secreted by C. albicans, is thought to play an important role in the development of C. albicans biofilms and is also a virulence factor. This study evaluated whether C. albicans bloodstream infection (BSI) strains belonging to different MLST clades secrete different levels of E,E-farnesol (FOH) and whether they have different clinical characteristics. In total, 149 C. albicans BSI isolates from ten Korean hospitals belonging to clades 18 (n = 28), 4 (n = 23), 1 (n = 22), 12 (n = 17), and other clades (n = 59) were assessed. For each isolate, the FOH level in 24-hour biofilms was determined in filtered (0.45 MUm) culture supernatant using high performance liquid chromatography. Marked differences in FOH secretion from biofilms (0.10-6.99 MUM) were observed among the 149 BSI isolates. Clade 18 isolates secreted significantly more FOH than did non-clade 18 isolates (mean +/- SEM; 2.66 +/- 0.22 vs. 1.69 +/- 0.10 MUM; P < 0.001). Patients with isolates belonging to clade 18 had a lower mean severity of illness than other patients, as measured using the "acute physiology and chronic health evaluation" (APACHE) III score (14.4 +/- 1.1 vs. 18.0 +/- 0.7; P < 0.05). This study provides evidence that C. albicans BSI isolates belonging to the most prevalent MLST clade (clade 18) in Korea are characterized by increased levels of FOH secretion and less severe illness. PMID- 26848579 TI - Prefrontal Neurons Encode Actions and Outcomes in Conjunction with Spatial Location in Rats Performing a Dynamic Delayed Non-Match to Position Task. AB - To respond adaptively to change organisms must utilize information about recent events and environmental context to select actions that are likely to produce favorable outcomes. We developed a dynamic delayed nonmatching to position task to study the influence of spatial context on event-related activity of medial prefrontal cortex neurons during reinforcement-guided decision-making. We found neurons with responses related to preparation, movement, lever press responses, reinforcement, and memory delays. Combined event-related and video tracking analyses revealed variability in spatial tuning of neurons with similar event related activity. While all correlated neurons exhibited spatial tuning broadly consistent with relevant task events, for instance reinforcement-related activity concentrated in locations where reinforcement was delivered, some had elevated activity in more specific locations, for instance reinforcement-related activity in one of several locations where reinforcement was delivered. Timing analyses revealed a limited set of distinct response types with activity time-locked to critical behavioral events that represent the temporal organization of dDNMTP trials. Our results suggest that reinforcement-guided decision-making emerges from discrete populations of medial prefrontal neurons that encode information related to planned or ongoing movements and actions and anticipated or actual action-outcomes in conjunction with information about spatial context. PMID- 26848578 TI - Global Metabolic Responses to Salt Stress in Fifteen Species. AB - Cells constantly adapt to unpredictably changing extracellular solute concentrations. A cornerstone of the cellular osmotic stress response is the metabolic supply of energy and building blocks to mount appropriate defenses. Yet, the extent to which osmotic stress impinges on the metabolic network remains largely unknown. Moreover, it is mostly unclear which, if any, of the metabolic responses to osmotic stress are conserved among diverse organisms or confined to particular groups of species. Here we investigate the global metabolic responses of twelve bacteria, two yeasts and two human cell lines exposed to sustained hyperosmotic salt stress by measuring semiquantitative levels of hundreds of cellular metabolites using nontargeted metabolomics. Beyond the accumulation of osmoprotectants, we observed significant changes of numerous metabolites in all species. Global metabolic responses were predominantly species-specific, yet individual metabolites were characteristically affected depending on species' taxonomy, natural habitat, envelope structure or salt tolerance. Exploiting the breadth of our dataset, the correlation of individual metabolite response magnitudes across all species implicated lower glycolysis, tricarboxylic acid cycle, branched-chain amino acid metabolism and heme biosynthesis to be generally important for salt tolerance. Thus, our findings place the global metabolic salt stress response into a phylogenetic context and provide insights into the cellular phenotype associated with salt tolerance. PMID- 26848581 TI - The Presence of Clitoromegaly in the Nonclassical Form of 21-Hydroxylase Deficiency Could Be Partially Modulated by the CAG Polymorphic Tract of the Androgen Receptor Gene. AB - BACKGROUND: In the nonclassical form (NC), good correlation has been observed between genotypes and 17OH-progesterone (17-OHP) levels. However, this correlation was not identified with regard to the severity of hyperandrogenic manifestations, which could depend on interindividual variability in peripheral androgen sensitivity. Androgen action is modulated by the polymorphic CAG tract (nCAG) of the androgen receptor (AR) gene and by polymorphisms in 5alpha reductase type 2 (SRD5A2) enzyme, both of which are involved in the severity of hyperandrogenic disorders. OBJECTIVES: To analyze whether nCAG-AR and SRD5A2 polymorphisms influence the severity of the nonclassical phenotype. PATIENTS: NC patients (n = 114) diagnosed by stimulated-17OHP >=10 ng/mL were divided into groups according to the beginning of hyperandrogenic manifestations (pediatric and adolescent/adult) and CYP21A2 genotypes (C/C: homozygosis for mild mutations; A/C: compound heterozygosis for severe/mild mutations). METHODS: CYP21A2 mutations were screened by allelic-specific PCR, MLPA and/or sequencing. HpaII digested and HpaII-undigested DNA samples underwent GeneScan analysis to study nCAG, and the SRD5A2 polymorphisms were screened by RLFP. RESULTS: Mean nCAG did not differ among pediatric, adolescent/adult and asymptomatic subjects. In the C/C genotype, we observed a significantly lower frequency of longer CAG alleles in pediatric patients than in adolescent/adults (p = 0.01). In patients carrying the A/C genotype, the frequencies of shorter and longer CAG alleles did not differ between pediatric patients and adolescent/adults (p>0.05). Patients with clitoromegaly had significantly lower weighted CAG biallelic mean than those without it: 19.1+/-2.7 and 21.6+/-2.5, respectively (p = 0.007), independent of the CYP21A2 genotype's severity. The SRD5A2 polymorphisms were not associated with the variability of hyperandrogenic NC phenotypes. CONCLUSIONS: In this series, we observed a modulatory effect of the CAG-AR tract on clinical manifestations of the NC form. Although the NC form is a monogenic disorder, our preliminary data suggested that the interindividual variability of the hyperandrogenic phenotype could arise from polygenic interactions. PMID- 26848582 TI - Evaluating Cell Processes, Quality, and Biomarkers in Pluripotent Stem Cells Using Video Bioinformatics. AB - There is a foundational need for quality control tools in stem cell laboratories engaged in basic research, regenerative therapies, and toxicological studies. These tools require automated methods for evaluating cell processes and quality during in vitro passaging, expansion, maintenance, and differentiation. In this paper, an unbiased, automated high-content profiling toolkit, StemCellQC, is presented that non-invasively extracts information on cell quality and cellular processes from time-lapse phase-contrast videos. Twenty four (24) morphological and dynamic features were analyzed in healthy, unhealthy, and dying human embryonic stem cell (hESC) colonies to identify those features that were affected in each group. Multiple features differed in the healthy versus unhealthy/dying groups, and these features were linked to growth, motility, and death. Biomarkers were discovered that predicted cell processes before they were detectable by manual observation. StemCellQC distinguished healthy and unhealthy/dying hESC colonies with 96% accuracy by non-invasively measuring and tracking dynamic and morphological features over 48 hours. Changes in cellular processes can be monitored by StemCellQC and predictions can be made about the quality of pluripotent stem cell colonies. This toolkit reduced the time and resources required to track multiple pluripotent stem cell colonies and eliminated handling errors and false classifications due to human bias. StemCellQC provided both user specified and classifier-determined analysis in cases where the affected features are not intuitive or anticipated. Video analysis algorithms allowed assessment of biological phenomena using automatic detection analysis, which can aid facilities where maintaining stem cell quality and/or monitoring changes in cellular processes are essential. In the future StemCellQC can be expanded to include other features, cell types, treatments, and differentiating cells. PMID- 26848580 TI - Effects of vitamin D supplementation on endothelial function: a systematic review and meta-analysis of randomised clinical trials. AB - BACKGROUND: In addition to regulating calcium homoeostasis and bone health, vitamin D influences vascular and metabolic processes including endothelial function (EF) and insulin signalling. This systematic review and meta-analysis of randomised clinical trials (RCTs) were conducted to investigate the effect of vitamin D supplementation on EF and to examine whether the effect size was modified by health status, study duration, dose, route of vitamin D administration, vitamin D status (baseline and post-intervention), body mass index (BMI), age and type of vitamin D. METHODS: We searched the Medline, Embase, Cochrane Library and Scopus databases from inception until March 2015 for studies meeting the following criteria: (1) RCT with adult participants, (2) vitamin D administration alone, (3) studies that quantified EF using commonly applied methods including ultrasound, plethysmography, applanation tonometry and laser Doppler. RESULTS: Sixteen articles reporting data for 1177 participants were included. Study duration ranged from 4 to 52 weeks. The effect of vitamin D on EF was not significant (SMD: 0.08, 95 % CI -0.06, 0.22, p = 0.28). Subgroup analysis showed a significant improvement of EF in diabetic subjects (SMD: 0.31, 95 % CI 0.05, 0.57, p = 0.02). A non-significant trend was found for diastolic blood pressure (beta = 0.02; p = 0.07) and BMI (beta = 0.05; p = 0.06). CONCLUSIONS: Vitamin D supplementation did not improve EF. The significant effect of vitamin D in diabetics and a tendency for an association with BMI may indicate a role of excess adiposity and insulin resistance in modulating the effects of vitamin D on vascular function. This remains to be tested in future studies. PMID- 26848583 TI - A Qualitative Study of Service Provision for Alcohol Related Health Issues in Mid to Later Life. AB - AIMS: Epidemiological surveys over the last 20 years show a steady increase in the amount of alcohol consumed by older age groups. Physiological changes and an increased likelihood of health problems and medication use make older people more likely than younger age groups to suffer negative consequences of alcohol consumption, often at lower levels. However, health services targeting excessive drinking tend to be aimed at younger age groups. The aim of this study was to gain an in-depth understanding of experiences of, and attitudes towards, support for alcohol related health issues in people aged 50 and over. METHODS: Qualitative interviews (n = 24, 12 male/12 female, ages 51-90 years) and focus groups (n = 27, 6 male/21 female, ages 50-95 years) were carried out with a purposive sample of participants who consumed alcohol or had been dependent. FINDINGS: Participants' alcohol misuse was often covert, isolated and carefully regulated. Participants tended to look first to their General Practitioner for help with alcohol. Detoxification courses had been found effective for dependent participants but only in the short term; rehabilitation facilities were appreciated but seen as difficult to access. Activities, informal groups and drop in centres were endorsed. It was seen as difficult to secure treatment for alcohol and mental health problems together. Barriers to seeking help included functioning at a high level, concern about losing positive aspects of drinking, perceived stigma, service orientation to younger people, and fatalistic attitudes to help-seeking. Facilitators included concern about risk of fatal illness or pressure from significant people. CONCLUSION: Primary care professionals need training on improving the detection and treatment of alcohol problems among older people. There is also a compelling need to ensure that aftercare is in place to prevent relapse. Strong preferences were expressed for support to be provided by those who had experienced alcohol problems themselves. PMID- 26848584 TI - Stable Ectopic Expression of ST6GALNAC5 Induces Autocrine MET Activation and Anchorage-Independence in MDCK Cells. AB - The epithelial-mesenchymal transition (EMT) is a complex cancer progression that can boost the metastatic potential of transformed cells by inducing migration, loss of cell adhesion, and promoting proliferation under anchorage-independent conditions. A DNA microarray analysis was performed comparing parental anchorage dependent MDCK cells and anchorage-independent MDCK cells that were engineered to express human siat7e (ST6GALNAC5). The comparison identified several genes involved in the EMT process that were differentially expressed between the anchorage-dependent and the anchorage-independent MDCK cell lines. The hepatocyte growth factor gene (hgf) was found to be over-expressed in the engineered MDCK siat7e cells at both transcription and protein expression levels. Phosphorylation analysis of the MET receptor tyrosine kinase confirmed the activation of an autocrine loop of the HGF/ MET signaling pathway in the MDCK-siat7e cells. When MET activities were suppressed by using the small-molecular inhibitor drug PF 02341066 (Crizotinib), the anchorage-independent MDCK-siat7e cells reverted to the cellular morphology of the parental anchorage-dependent MDCK cells. These observations indicate that the MET receptor plays a central role in the growth properties of the MDCK cells and its phosphorylation status is likely dependent on sialylation. Further investigation of the downstream signaling targets in the MET network showed that the degree of MDCK cell adhesion correlated with secretion levels of a matrix metalloproteinase, MMP1, suggesting a role of metalloproteinases in the EMT process. These results demonstrate that in addition to its application in biotechnology processes, MDCK-siat7e may serve as a model cell for metastasis studies to decipher the sequence of events leading up to the activation of EMT. PMID- 26848585 TI - Clinical utility of endoscopic ultrasound-guided fine-needle aspiration in mixed adenoneuroendocrine carcinoma with signet-ring cells of the pancreas: a case report and review of the literature. AB - A man in his 60s visited our hospital because of a pancreatic head tumor. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) revealed that the tumor consisted of a neuroendocrine carcinoma (NEC) and adenocarcinoma, including signet-ring cell carcinoma, and that the ratio of these components was approximately 50:50. Therefore, he was diagnosed with mixed adenoneuroendocrine carcinoma (MANEC). Because of liver and lymph node metastases, systemic chemotherapy was initiated using a regimen for the NEC component based on an increase in neuron-specific enolase (NSE). Although the patient achieved stable disease after two chemotherapy cycles, the tumor increased in size after three cycles, which was associated with a gradual increase in carcinoembryonic antigen and a decrease in NSE level. An EUS-FNA reexamination revealed that the adenocarcinoma component accounted for 90 % of the tumor. Thus, an adenocarcinoma chemotherapy regimen was started, and a slight reduction in tumor size was observed. Here, we report an extremely rare and remarkable case of MANEC of the pancreas that demonstrates the effectiveness of EUS-FNA for helping to decide the chemotherapy regimen. PMID- 26848586 TI - Nucleolar DEAD-Box RNA Helicase TOGR1 Regulates Thermotolerant Growth as a Pre rRNA Chaperone in Rice. AB - Plants have evolved a considerable number of intrinsic tolerance strategies to acclimate to ambient temperature increase. However, their molecular mechanisms remain largely obscure. Here we report a DEAD-box RNA helicase, TOGR1 (Thermotolerant Growth Required1), prerequisite for rice growth themotolerance. Regulated by both temperature and the circadian clock, its expression is tightly coupled to daily temperature fluctuations and its helicase activities directly promoted by temperature increase. Located in the nucleolus and associated with the small subunit (SSU) pre-rRNA processome, TOGR1 maintains a normal rRNA homeostasis at high temperature. Natural variation in its transcript level is positively correlated with plant height and its overexpression significantly improves rice growth under hot conditions. Our findings reveal a novel molecular mechanism of RNA helicase as a key chaperone for rRNA homeostasis required for rice thermotolerant growth and provide a potential strategy to breed heat tolerant crops by modulating the expression of TOGR1 and its orthologs. PMID- 26848587 TI - Syntaxin-3 Binds and Regulates Both R- and L-Type Calcium Channels in Insulin Secreting INS-1 832/13 Cells. AB - Syntaxin (Syn)-1A mediates exocytosis of predocked insulin-containing secretory granules (SGs) during first-phase glucose-stimulated insulin secretion (GSIS) in part via its interaction with plasma membrane (PM)-bound L-type voltage-gated calcium channels (Cav). In contrast, Syn-3 mediates exocytosis of newcomer SGs that accounts for second-phase GSIS. We now hypothesize that the newcomer SG Syn 3 preferentially binds and modulates R-type Cav opening, which was postulated to mediate second-phase GSIS. Indeed, glucose-stimulation of pancreatic islet beta cell line INS-1 induced a predominant increase in interaction between Syn-3 and Cavalpha1 pore-forming subunits of R-type Cav2.3 and to lesser extent L-type Cavs, while confirming the preferential interactions between Syn-1A with L-type (Cav1.2, Cav1.3) Cavs. Consistently, direct binding studies employing heterologous HEK cells confirmed that Syn-3 preferentially binds Cav2.3, whereas Syn-1A prefers L-type Cavs. We then used siRNA knockdown (KD) of Syn-3 in INS-1 to study the endogenous modulatory actions of Syn-3 on Cav channels. Syn-3 KD enhanced Ca2+ currents by 46% attributed mostly to R- and L-type Cavs. Interestingly, while the transmembrane domain of Syn-1A is the putative functional domain modulating Cav activity, it is the cytoplasmic domain of Syn-3 that appears to modulate Cav activity. We conclude that Syn-3 may mimic Syn-1A in the ability to bind and modulate Cavs, but preferring Cav2.3 to perhaps participate in triggering fusion of newcomer insulin SGs during second-phase GSIS. PMID- 26848588 TI - Quantitative Imaging Biomarkers of NAFLD. AB - Conventional imaging modalities, including ultrasonography (US), computed tomography (CT), and magnetic resonance (MR), play an important role in the diagnosis and management of patients with nonalcoholic fatty liver disease (NAFLD) by allowing noninvasive diagnosis of hepatic steatosis. However, conventional imaging modalities are limited as biomarkers of NAFLD for various reasons. Multi-parametric quantitative MRI techniques overcome many of the shortcomings of conventional imaging and allow comprehensive and objective evaluation of NAFLD. MRI can provide unconfounded biomarkers of hepatic fat, iron, and fibrosis in a single examination-a virtual biopsy has become a clinical reality. In this article, we will review the utility and limitation of conventional US, CT, and MR imaging for the diagnosis NAFLD. Recent advances in imaging biomarkers of NAFLD are also discussed with an emphasis in multi parametric quantitative MRI. PMID- 26848589 TI - The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice. AB - Lyme disease, Borrelia burgdorferi-caused infection, if not recognized and appropriately treated by antibiotics, may lead to chronic complications, thus stressing the need for protective vaccine development. The immune protection is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies, associated with the Th1 immune response. Surface antigen OspC is involved in Borrelia spreading through the host body. Previously we reported that recombinant histidine tagged (His-tag) OspC (rOspC) could be attached onto liposome surfaces by metallochelation. Here we report that levels of OspC specific antibodies vary substantially depending upon whether rOspC possesses an N' or C' terminal His-tag. This is the case in mice immunized: (a) with rOspC proteoliposomes containing adjuvants MPLA or non-pyrogenic MDP analogue MT06; (b) with free rOspC and Montanide PET GEL A; (c) with free rOspC and alum; or (d) with adjuvant-free rOspC. Stronger responses are noted with all N'-terminal His tag rOspC formulations. OspC-specific Th1-type antibodies predominate post immunization with rOspC proteoliposomes formulated with MPLA or MT06 adjuvants. Further analyses confirmed that the structural features of soluble N' and C' terminal His-tag rOspC and respective rOspC proteoliposomes are similar including their thermal stabilities at physiological temperatures. On the other hand, a change in the position of the rOspC His-tag from N' to C' terminal appears to affect substantially the immunogenicity of rOspC arguably due to steric hindrance of OspC epitopes by the C' terminal His-tag itself and not due to differences in overall conformations induced by changes in the His-tag position in rOspC variants. PMID- 26848591 TI - Cytopathological Evaluation of Ocular Surface and Needle Washings Following Intravitreal Melphalan Injections for Retinoblastoma. AB - PURPOSE: There is concern that injections into eyes with retinoblastoma are dangerous and allow tumor escapement. This study attempted to determine this risk by investigating the presence of malignant cells in ocular surface and needle washings of eyes with retinoblastoma receiving intravitreal injections. METHODS: Two hundred ocular surface and 202 needle washings were obtained from 280 injections into eyes with retinoblastoma. Each specimen underwent cytopathlogical assessment for the presence of malignant cells. RESULTS: Cytopathological results revealed no malignant cells in all 200 ocular surface and 202 needle washing specimens. In the ocular surface washings, squamous cells, red blood cells, and inflammatory cells were found in 15, 2, and 2 specimens, respectively. In the needle washings, 4 specimens contained squamous cells but no red blood cells or inflammatory cells were found in any specimen. CONCLUSION: With this injection and evaluation technique, no malignant cells were recovered, highlighting the low risk of the procedure. [J Pediatr Opthalmol Strabismus. 20XX;XX(XX):XX-XX.]. PMID- 26848590 TI - Presynaptic GABAB Receptors Regulate Hippocampal Synapses during Associative Learning in Behaving Mice. AB - GABAB receptors are the G-protein-coupled receptors for GABA, the main inhibitory neurotransmitter in the central nervous system. Pharmacological activation of GABAB receptors regulates neurotransmission and neuronal excitability at pre- and postsynaptic sites. Electrophysiological activation of GABAB receptors in brain slices generally requires strong stimulus intensities. This raises the question as to whether behavioral stimuli are strong enough to activate GABAB receptors. Here we show that GABAB1a-/- mice, which constitutively lack presynaptic GABAB receptors at glutamatergic synapses, are impaired in their ability to acquire an operant learning task. In vivo recordings during the operant conditioning reveal a deficit in learning-dependent increases in synaptic strength at CA3-CA1 synapses. Moreover, GABAB1a-/- mice fail to synchronize neuronal activity in the CA1 area during the acquisition process. Our results support that activation of presynaptic hippocampal GABAB receptors is important for acquisition of a learning task and for learning-associated synaptic changes and network dynamics. PMID- 26848592 TI - Inferior Oblique Botulinum Toxin Injection: A Postoperative Diplopia Test for Secondary Inferior Oblique Muscle Overaction. AB - PURPOSE: To evaluate the utility of botulinum toxin injection into the inferior oblique muscle for secondary inferior oblique muscle overaction. METHODS: A retrospective review of 18 patients and 23 injections performed over a 9-year period. Indications and deviations in primary position and contralateral gaze before and after injection were recorded. Functional outcomes and further management (conservative vs surgical) were observed. RESULTS: In 14 patients, chemodenervation resulted in a temporary improvement in symptoms. Eleven of these patients went on to have inferior oblique myectomy with resolution of their diplopia. Two patients preferred to receive regular injections of botulinum toxin as a treatment. CONCLUSIONS: Botulinum toxin chemodenervation of the inferior oblique muscle in cases of secondary inferior oblique muscle overaction is useful where one needs to establish a risk of overcorrection following planned inferior oblique muscle weakening. This is particularly true in cases where the primary position deviation may be small but symptoms of diplopia exist on contralateral side gaze, giving rise to a narrowed field of binocular single vision. PMID- 26848593 TI - Comparison of Clinical Features and Long-term Surgical Outcomes in Infantile Constant and Intermittent Exotropia. AB - PURPOSE: To evaluate the long-term surgical outcomes and the clinical features between infantile-onset constant and intermittent exotropia. METHODS: The medical records of 67 patients diagnosed as having infantile exotropia before 12 months of age who underwent surgery were reviewed retrospectively. Patients were divided into intermittent exotropia and constant exotropia groups based on presentation before surgery. All patients underwent bilateral lateral rectus recession. Preoperative and postoperative clinical features were investigated. RESULTS: There were 37 children in the intermittent exotropia group and 30 children in the constant exotropia group. The cumulative probabilities of success 3 years after bilateral lateral rectus recession were 91.9% in the intermittent exotropia group and 70% in the constant exotropia group. Constant deviation was more closely associated with both dissociated vertical deviation (DVD) and inferior oblique muscle overaction (IOOA) (P = .009 and P = .009, respectively) and related to poor stereopsis outcome (P = .002) and distance suppression (P = .029). CONCLUSIONS: Constant deviation was associated with the development of recurrence, DVD/IOOA, and poor stereopsis after surgery. Constancy of exotropia is a reliable factor for predicting poor surgical outcomes in infantile exotropia at long-term follow-up. PMID- 26848594 TI - Evaluation of immunochromatographic tests for the rapid detection of the emerging GII.17 norovirus in stool samples, January 2016. AB - A novel GII.17 norovirus emerged in Asia in the winter of 2014/15. A worldwide spread is conceivable and norovirus diagnostic assays need to be evaluated to investigate if they adequately detect this emerging genotype. Seven immunochromatographic kits commercially available in Europe were evaluated on ten stool samples where GII.17 virus had been quantified by real-time reverse transcription-polymerase chain reaction. All the kits detected GII.17 with various sensitivities, partly depending on the virus titre. PMID- 26848595 TI - Fluorophore Assisted Photolysis of Thiolato-Cob(III)alamins. AB - Cobalamins are known to react with thiols to yield stable beta-axial Co(III)-S bonded thiolato-cobalamin complexes. However, in stark contrast to the Co-C bond in alkylcobalamins, the photolability of the Co-S bond in thiolato-cobalamins remains undetermined. We have investigated the photolysis of N-acetylcysteinyl cob(III)alamin at several wavelengths within the ultraviolet and visible spectrum. To aid in photolysis, we show that attaching fluorophore "antennae" to the cobalamin scaffold can improve photolytic efficiency by up to an order of magnitude. Additionally, electron paramagnetic resonance confirms previous conjectures that the photolysis of thiolato-cobalamins at wavelengths as long as 546 nm produces thiyl radicals. PMID- 26848596 TI - X-ray and Neutron Scattering Study of the Formation of Core-Shell-Type Polyoxometalates. AB - A typical type of core-shell polyoxometalates can be obtained through the Keggin type polyoxometalate-templated growth of a layer of spherical shell structure of {Mo72Fe30}. Small-angle X-ray scattering is used to study the structural features and stability of the core-shell structures in aqueous solutions. Time-resolved small-angle X-ray scattering is applied to monitor the synthetic reactions, and a three-stage formation mechanism is proposed to describe the synthesis of the core shell polyoxometalates based on the monitoring results. New protocols have been developed by fitting the X-ray data with custom physical models, which provide more convincing, objective, and completed data interpretation. Quasi-elastic and inelastic neutron scattering are used to probe the dynamics of water molecules in the core-shell structures, and two different types of water molecules, the confined and structured water, are observed. These water molecules play an important role in bridging core and shell structures and stabilizing the cluster structures. PMID- 26848597 TI - Under Pressure: Reduced Cerebral Perfusion as a Risk Factor for Postoperative Delirium in Lung Transplant Recipients. PMID- 26848598 TI - Increased Costs of the Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome. One Syndrome for the Price of Two? PMID- 26848599 TI - Shining the Light on Sepsis. PMID- 26848600 TI - Not Every Drip Needs a Plumber. Continuous Sedation for Alcohol Withdrawal Syndrome May Not Require Intubation. PMID- 26848602 TI - A Noteworthy Case of Acute Bronchitis. PMID- 26848603 TI - Hemodynamic Consequences of a Surgical Arteriovenous Fistula. PMID- 26848601 TI - The Critical Role of Pulmonary Arterial Compliance in Pulmonary Hypertension. AB - The normal pulmonary circulation is a low-pressure, high-compliance system. Pulmonary arterial compliance decreases in the presence of pulmonary hypertension because of increased extracellular matrix/collagen deposition in the pulmonary arteries. Loss of pulmonary arterial compliance has been consistently shown to be a predictor of increased mortality in patients with pulmonary hypertension, even more so than pulmonary vascular resistance in some studies. Decreased pulmonary arterial compliance causes premature reflection of waves from the distal pulmonary vasculature, leading to increased pulsatile right ventricular afterload and eventually right ventricular failure. Evidence suggests that decreased pulmonary arterial compliance is a cause rather than a consequence of distal small vessel proliferative vasculopathy. Pulmonary arterial compliance decreases early in the disease process even when pulmonary artery pressure and pulmonary vascular resistance are normal, potentially enabling early diagnosis of pulmonary vascular disease, especially in high-risk populations. With the recognition of the prognostic importance of pulmonary arterial compliance, its impact on right ventricular function, and its contributory role in the development and progression of distal small-vessel proliferative vasculopathy, pulmonary arterial compliance is an attractive target for the treatment of pulmonary hypertension. PMID- 26848604 TI - Progressive Dyspnea in a Patient with Asthma. Insights on Computed Tomographic Imaging of the Airway. PMID- 26848605 TI - Implementation and Evaluation of a Stock Albuterol Program for Students with Asthma. PMID- 26848606 TI - Resolution of Intestinal Histopathology Changes in Cystic Fibrosis after Treatment with Ivacaftor. PMID- 26848607 TI - Characteristics of Pleural Effusions in Acute Idiopathic Pericarditis and Post Cardiac Injury Syndrome. PMID- 26848610 TI - "NextGen" Biologics: Bispecific Antibodies and Emerging Clinical Results. AB - INTRODUCTION: Bispecific antibodies (BsAb) are emerging as a novel approach for dual targeting strategies. Two bispecific antibodies are approved for therapy and >30 are in clinical development. The first generation of BsAb were produced by chemical cross-linking or hybridoma technology; with the recent advent of genetic and protein engineering technologies numerous formats of bispecific antibodies have emerged using either the fragments of IgG or whole IgG molecules. Further areas of development include dual blockade of different disease pathways, diagnosis and imaging. AREAS COVERED: Biologics, including bi- or multi-specific antibodies and T cell-based approaches are rapidly changing the landscape of cancer therapeutics. New engineering platforms for bi- or multi-specific antibodies and scaffolds offer improved efficacy and reduced toxicities over IgG based monoclonal antibodies. Preclinical and clinical studies using different formats of BsAbs are described in this review using PubMed as a literature search tool. EXPERT OPINION: A comprehensive presentation of preclinical data and clinical trials evaluating the various formats of BsAbs indicate their safety and efficacy. However, a vast opportunity to fine tune physical properties and functional activity of biologics to improve the stability, engagement of cytotoxic CD8 T cells and multi-antigen targeting strategy through protein engineering holds a greater therapeutic potential. PMID- 26848611 TI - Characterization of Adsorbed Molecular Water on the Surface of a Stretched Polytetrafluoroethylene Tape Analyzed by (1)H NMR. AB - A single molecule often exhibits a largely different material character from a bulk matter. Although a perfluoroalkyl (Rf) compound is a representative one, many interests have mostly been devoted to the bulk character only thus far, leaving the single molecular character unclear. Recently, a new theoretical framework, stratified dipole-arrays (SDA) theory, has appeared for comprehensive understanding of Rf compounds in terms of both single and bulk systems. On this theory, a mechanically stretched polytetrafluoroethylene (PTFE) is expected to exhibit a single-molecular character having dipole-driven properties, which should attract molecular water. In the present study, a stretched PTFE tape is revealed to attract molecular water (not water droplet) in fact, and the adsorbed water molecules are highly restricted in motion by the dipole-dipole interaction studied by using (1)H NMR, which agrees with the prediction by the SDA theory. PMID- 26848609 TI - An Official American Thoracic Society/European Respiratory Society Workshop Report: Evaluation of Respiratory Mechanics and Function in the Pediatric and Neonatal Intensive Care Units. AB - Ready access to physiologic measures, including respiratory mechanics, lung volumes, and ventilation/perfusion inhomogeneity, could optimize the clinical management of the critically ill pediatric or neonatal patient and minimize lung injury. There are many techniques for measuring respiratory function in infants and children but very limited information on the technical ease and applicability of these tests in the pediatric and neonatal intensive care unit (PICU, NICU) environments. This report summarizes the proceedings of a 2011 American Thoracic Society Workshop critically reviewing techniques available for ventilated and spontaneously breathing infants and children in the ICU. It outlines for each test how readily it is performed at the bedside and how it may impact patient management as well as indicating future areas of potential research collaboration. From expert panel discussions and literature reviews, we conclude that many of the techniques can aid in optimizing respiratory support in the PICU and NICU, quantifying the effect of therapeutic interventions, and guiding ventilator weaning and extubation. Most techniques now have commercially available equipment for the PICU and NICU, and many can generate continuous data points to help with ventilator weaning and other interventions. Technical and validation studies in the PICU and NICU are published for the majority of techniques; some have been used as outcome measures in clinical trials, but few have been assessed specifically for their ability to improve clinical outcomes. Although they show considerable promise, these techniques still require further study in the PICU and NICU together with increased availability of commercial equipment before wider incorporation into daily clinical practice. PMID- 26848612 TI - The role of solithromycin in the management of bacterial community-acquired pneumonia. AB - The fluoroketolide solithromycin is 2-fold more potent in vitro than telithromycin against pneumococci (including macrolide-resistant strains) and Haemophilus influenzae and very active on pathogens causing atypical pneumonia. In contrast, it is a 30-fold less potent inhibitor of nicotinic receptors incriminated in telithromycin toxicity. In Phase II/III trials, oral solithromycin once-daily (800 mg on day 1; 400 mg on days 2-5) proved effective and safe when compared to respiratory fluoroquinolones for the treatment of community-acquired bacterial pneumonia (CABP). A Phase III intravenous trial vs. moxifloxacin has been recently completed for the same indication. Solithromycin may restore interest in ketolides as a first-line therapy for CAPB. Solithromycin safety should nevertheless be confirmed in larger populations allowing for detection of rare adverse events. PMID- 26848613 TI - Benefits of Regulating Hazardous Air Pollutants from Coal and Oil-Fired Utilities in the United States. PMID- 26848614 TI - Association between IL-27 2905T/G genotypes and the risk and survival of cervical cancer: a case-control study. AB - BACKGROUND: Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. PATIENTS AND METHODS: A case control study was conducted to investigate the possible associations of IL-27 gene polymorphisms with susceptibility to cervical cancer and clinical outcome. RESULTS: Our results suggested that the IL-27 2905T/G was significantly associated with a decreased risk of cervical cancer. Further analysis showed IL 27 2905T/G genotypes were associated with advanced tumor stages of cervical cancer patients. More interestingly, the IL-27 2905T/G genotypes were statistically significantly associated with the survival in cervical cancer patients. CONCLUSION: Our results showed that the IL-27 2905T/G genotypes were associated with decreased the susceptibility and development of cervical cancer in Chinese Han population. PMID- 26848615 TI - The Notch pathway promotes the cancer stem cell characteristics of CD90+ cells in hepatocellular carcinoma. AB - CD90 has been identified as a marker for liver cancer stem cells (CSCs) that are responsible for tumorigenic activity, but it is not known how CD90+ cells contribute to tumor initiation and progression. Our data demonstrated that high expression of CD90 in Hepatocellular Carcinoma (HCC) tissues correlated with venous filtration in HCC patients. CD90+ cells isolated from HCC cell lines exhibited increased tumorigenicity, chemoresistance, tumor invasion and metastasis. Notch pathway was activated in CD90+ cells and we found that inhibition of Notch pathway in CD90+ CSCs decreased tumorigenicity, cell invasion, migration and expression of stem cell related genes. Activation of Notch pathway in CD90- cells induced self-renewal, invasion and migration. Furthermore, we observed that cancer stem cell features were facilitated by stimulating G1-S transition in the cell cycle phase and inhibiting apoptosis mediated by Notch pathway. Our findings suggested CD90 could be used as a potential biomarker for HCC CSCs, and that cancer stem cell activity was elevated through up activated Notch pathway in CD90+ CSCs. PMID- 26848616 TI - The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression. AB - Neuroblastoma is the most common solid tumor during early childhood. One of the key features of neuroblastoma is extensive tumor-driven angiogenesis due to hypoxia. However, the mechanism through which neuroblastoma cells drive angiogenesis is poorly understood. Here we show that the long noncoding RNA MALAT1 was upregulated in human neuroblastoma cell lines under hypoxic conditions. Conditioned media from neuroblastoma cells transfected with small interfering RNAs (siRNA) targeting MALAT1, compared with conditioned media from neuroblastoma cells transfected with control siRNAs, induced significantly less endothelial cell migration, invasion and vasculature formation. Microarray-based differential gene expression analysis showed that one of the genes most significantly down-regulated following MALAT1 suppression in human neuroblastoma cells under hypoxic conditions was fibroblast growth factor 2 (FGF2). RT-PCR and immunoblot analyses confirmed that MALAT1 suppression reduced FGF2 expression, and Enzyme-Linked Immunosorbent Assays revealed that transfection with MALAT1 siRNAs reduced FGF2 protein secretion from neuroblastoma cells. Importantly, addition of recombinant FGF2 protein to the cell culture media reversed the effects of MALAT1 siRNA on vasculature formation. Taken together, our data suggest that up-regulation of MALAT1 expression in human neuroblastoma cells under hypoxic conditions increases FGF2 expression and promotes vasculature formation, and therefore plays an important role in tumor-driven angiogenesis. PMID- 26848617 TI - Intratumoral KIT mutational heterogeneity and recurrent KIT/ PDGFRA mutations in KIT/PDGFRA wild-type gastrointestinal stromal tumors. AB - OBJECTIVE: Gastrointestinal stromal tumors (GISTs) with no mutations in exons 9, 11, 13, and 17 of the KIT gene and exons 12, and 18 of the PDGFRA gene were defined as KIT/PDGFRA wild-type and they accounted for ~15-20% of GISTs. However, some KIT/PDGFRA wild-type GISTs with KIT mutations in other exons were occasionally reported. We therefore assessed GISTs to understand the whole genomic genotypes of KIT or PDGFRA genes in KIT/PDGFRA wild-type GISTs. METHODS: A cohort of 185 KIT/PDGFRA wild-type GISTs from 1,080 cases was retrospectively assessed. Thirty-nine patients were excluded due to insufficiency of genomic DNA data or failure of library preparation, and 146 patients were analyzed by targeted next-generation sequencing (NGS) followed by validation. RESULTS: For hot spots in KIT and PDGFRA genes, 23 out of 146 KIT/PDGFRA wild-type cases carried mutations according to NGS; there were 19 KIT mutations and 4 PDGFRA mutations, and these were exclusive. Intratumoral KIT mutational heterogeneity was observed in 4 of 19 samples which potentially triggered mechanisms of polyclonal evolution and metastasis and drug sensitivity. Eleven patients treated with imatinib were evaluable for clinical response, and 2 of 3 patients with KIT mutations achieved partial response (PR), while only 1 of 8 patients without KIT mutations reached PR. CONCLUSION: NGS had the potential property to identify partial mutant tumors from a subset of GISTs regarded as KIT/PDGFRA wild-type tumors using Sanger sequencing, and provided a better understanding of KIT/PDGFRA genotypes as well as identified patients eligible for imatinib therapy. PMID- 26848620 TI - Smad4-dependent suppressor pituitary homeobox 2 promotes PPP2R2A-mediated inhibition of Akt pathway in pancreatic cancer. AB - The importance of Pituitary homeobox 2 (Pitx2) in malignancy remains enigmatic, and Pitx2 has not been previously implicated in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed gene expression profiling of human PDAC tissues and identified Pitx2 as a promising candidate. Pitx2 expression was decreased from 2.6- to 19-fold in human PDAC tissues from microarray units. Immunochemistry staining showed that Pitx2 expression was moderate to intense in normal pancreatic and pancreatic intraepithelial neoplastic lesions, whereas low in human PDAC tissues. The Pitx2 levels correlated with overall patient survival post-operatively in PDAC. Induction of Pitx2 expression partly inhibited the malignant phenotype of PDAC cells. Interestingly, low Pitx2 expression was correlated with Smad4 mutant inactivation, but not with Pitx2 DNA-methylation. Furthermore, Smad4 protein bound to Pitx2 promoter and stimulated Pitx2 expression in PDAC. In addition, Pitx2 protein bound to the promoter of the protein phosphatase 2A regulatory subunit B55alpha (PPP2R2A) and upregulated PPP2R2A expression, which may activate dephosphorylation of Akt in PDAC. These findings provide new mechanistic insights into Pitx2 as a tumor suppressor in the downstream of Smad4. And Pitx2 protein promotes PPP2R2A expression which may inhibit Akt pathway. Therefore, we propose that the Smad4-Pitx2-PPP2R2A axis, a new signaling pathway, suppresses the pancreatic carcinogenesis. PMID- 26848618 TI - Reelin promotes the adhesion and drug resistance of multiple myeloma cells via integrin beta1 signaling and STAT3. AB - Reelin is an extracellular matrix (ECM) protein that is essential for neuron migration and positioning. The expression of reelin in multiple myeloma (MM) cells and its association with cell adhesion and survival were investigated. Overexpression, siRNA knockdown, and the addition of recombinant protein of reelin were used to examine the function of reelin in MM cells. Clinically, high expression of reelin was negatively associated with progression-free survival and overall survival. Functionally, reelin promoted the adhesion of MM cells to fibronectin via activation of alpha5beta1 integrin. The resulting phosphorylation of Focal Adhesion Kinase (FAK) led to the activation of Src/Syk/STAT3 and Akt, crucial signaling molecules involved in enhancing cell adhesion and protecting cells from drug-induced cell apoptosis. These findings indicate reelin's important role in the activation of integrin-beta1 and STAT3/Akt pathways in multiple myeloma and highlight the therapeutic potential of targeting reelin/integrin/FAK axis. PMID- 26848619 TI - Bile acid-FXRalpha pathways regulate male sexual maturation in mice. AB - The bile acid receptor Farnesol-X-Receptor alpha (FRXalpha) is a member of the nuclear receptor superfamily. FRXalpha is expressed in the interstitial compartment of the adult testes, which contain the Leydig cells. In adult, short term treatment (12 hours) with FRXalpha agonist inhibits the expression of steroidogenic genes via the induction of the Small heterodimer partner (SHP). However the consequences of FRXalpha activation on testicular pathophysiology have never been evaluated. We demonstrate here that mice fed a diet supplemented with bile acid during pubertal age show increased incidence of infertility. This is associated with altered differentiation and increase apoptosis of germ cells due to lower testosterone levels. At the molecular level, next to the repression of basal steroidogenesis via the induction expression of Shp and Dax-1, two repressors of steroidogenesis, the main action of the BA-FRXalpha signaling is through lowering the Leydig cell sensitivity to the hypothalamo-pituitary axis, the main regulator of testicular endocrine function. In conclusion, BA-FRXalpha signaling is a critical actor during sexual maturation. PMID- 26848621 TI - Src drives the Warburg effect and therapy resistance by inactivating pyruvate dehydrogenase through tyrosine-289 phosphorylation. AB - The Warburg effect, which reflects cancer cells' preference for aerobic glycolysis over glucose oxidation, contributes to tumor growth, progression and therapy resistance. The restraint on pyruvate flux into mitochondrial oxidative metabolism in cancer cells is in part attributed to the inhibition of pyruvate dehydrogenase (PDH) complex. Src is a prominent oncogenic non-receptor tyrosine kinase that promotes cancer cell proliferation, invasion, metastasis and resistance to conventional and targeted therapies. However, the potential role of Src in tumor metabolism remained unclear. Here we report that activation of Src attenuated PDH activity and generation of reactive oxygen species (ROS). Conversely, Src inhibitors activated PDH and increased cellular ROS levels. Src inactivated PDH through direct phosphorylation of tyrosine-289 of PDH E1alpha subunit (PDHA1). Indeed, Src was the main kinase responsible for PDHA1 tyrosine phosphorylation in cancer cells. Expression of a tyrosine-289 non-phosphorable PDHA1 mutant in Src-hyperactivated cancer cells restored PDH activity, increased mitochondrial respiration and oxidative stress, decreased experimental metastasis, and sensitized cancer cells to pro-oxidant treatment. The results suggest that Src contributes to the Warburg phenotype by inactivating PDH through tyrosine phosphorylation, and the metabolic effect of Src is essential for Src driven malignancy and therapy resistance. Combination therapies consisting of both Src inhibitors and pro-oxidants may improve anticancer efficacy. PMID- 26848622 TI - Angiomotin promotes renal epithelial and carcinoma cell proliferation by retaining the nuclear YAP. AB - Renal cell carcinoma (RCC) is one of the common tumors in the urinary system without effective therapies. Angiomotin (Amot) can interact with Yes-associated protein (YAP) to either stimulate or inhibit YAP activity, playing a potential role in cell proliferation. However, the role of Amot in regulating the proliferation of renal epithelial and RCC cells is unknown. Here, we show that Amot is expressed predominantly in the nucleus of RCC cells and tissues, and in the cytoplasm and nucleus of renal epithelial cells and paracancerous tissues. Furthermore, Amot silencing inhibited proliferation of HK-2 and 786-O cells while Amot upregulation promoted proliferation of ACHN cells. Interestingly, the location of Amot and YAP in RCC clinical samples and cells was similar. Amot interacted with YAP in HK-2 and 786-O cells, particularly in the nucleus. Moreover, Amot silencing mitigated the levels of nuclear YAP in HK-2 and 786-O cells and reduced YAP-related CTGF and Cyr61 expression in 786-O cells. Amot upregulation slightly increased the nuclear YAP and YAP-related gene expression in ACHN cells. Finally, enhanced YAP expression restored proliferation of Amot silencing 786-O cells. Together, these data indicate that Amot is crucial for the maintenance of nuclear YAP to promote renal epithelial and RCC proliferation. PMID- 26848623 TI - eIF4B is a convergent target and critical effector of oncogenic Pim and PI3K/Akt/mTOR signaling pathways in Abl transformants. AB - Activation of eIF4B correlates with Abl-mediated cellular transformation, but the precise mechanisms are largely unknown. Here we show that eIF4B is a convergent substrate of JAK/STAT/Pim and PI3K/Akt/mTOR pathways in Abl transformants. Both pathways phosphorylated eIF4B in Abl-transformed cells, and such redundant regulation was responsible for the limited effect of single inhibitor on Abl oncogenicity. Persistent inhibition of one signaling pathway induced the activation of the other pathway and thereby restored the phosphorylation levels of eIF4B. Simultaneous inhibition of the two pathways impaired eIF4B phosphorylation more effectively, and synergistically induced apoptosis in Abl transformed cells and inhibited the growth of engrafted tumors in nude mice. Similarly, the survival of Abl transformants exhibited a higher sensitivity to the pharmacological inhibition, when combined with the shRNA-based silence of the other pathway. Interestingly, such synergy was dependent on the phosphorylation status of eIF4B on Ser422, as overexpression of eIF4B phosphomimetic mutant S422E in the transformants greatly attenuated the synergistic effects of these inhibitors on Abl oncogenicity. In contrast, eIF4B knockdown sensitized Abl transformants to undergo apoptosis induced by the combined blockage. Collectively, the results indicate that eIF4B integrates the signals from Pim and PI3K/Akt/mTOR pathways in Abl-expressing leukemic cells, and is a promising therapeutic target for such cancers. PMID- 26848626 TI - Targeting the PD-1 pathway in patients with relapsed classic Hodgkin lymphoma following allogeneic stem cell transplant is safe and effective. AB - Patients with classic Hodgkin lymphoma (cHL) that has relapsed after autologous or allogeneic transplant have limited treatment options and a poor prognosis. Immunotherapy with agents that target the PROGRAMMED DEATH 1 (PD-1) receptor have demonstrated clinical activity with durable responses in early-phase clinical trials in this patient population; however, patients with a history of allogeneic stem cell transplantation (SCT) were intentionally excluded from participation in those studies due to concerns for reactivation of graft-versus-host disease (GVHD). We describe the clinical course of two patients with advanced cHL and prior treatment with allogeneic stem cell transplantation (SCT) that were treated with the PD-1 inhibitor pembrolizumab. Both patients had no active graft-versus host disease (GVHD) at the time initiation of therapy and were maintained on low dose prednisone. Treatment with pembrolizumab was well tolerated and not associated with reactivation of GVHD. Both patients responded (1 partial, 1 complete) and remain on therapy as of November 30, 2015. This report indicates that immunotherapy targeting the PD-1 pathway can be safely administered to patients with cHL and a history of allogeneic SCT and produce tumor responses. Further studies in this patient population are needed. PMID- 26848625 TI - Long non-coding RNA FEZF1-AS1 facilitates cell proliferation and migration in colorectal carcinoma. AB - Long non-coding RNAs (lncRNA) have been shown to play important roles in the development and progression of cancer. Here, we discovered a novel long noncoding RNA (lncRNA) FEZF1 antisense RNA1 (FEZF1-AS1) is markedly upregulated in human primary colorectal carcinoma (CRC) and associated with CRC metastasis and poor prognosis. Moreover, the downregulation of FEZF1-AS1 expression significantly inhibited the CRC cells proliferation, migration and invasiveness, suppressed S phase entry in vitro, and repressed tumor growth and metastasis in vivo. In contrast, overexpression of FEZF1-AS1 could promote the aggressive behaviors of CRC cells. We further discovered that the downregulation of FEZF1-AS1 reduced its sense-cognate gene FEZF1 mRNA and protein expression in CRC cells. There was a positive correlation between FEZF1-AS1 and FEZF1 expression in CRC. Moreover, FEZF1 knockdown also significantly suppressed CRC cell proliferation, migration, and invasion. Our findings indicate that the dysregulation of FEZF1-AS1 participates in colorectal tumorigenesis and progression, which might be achieved, at least in part, through FEZF1 induction. PMID- 26848624 TI - Prognostic role of serum concentrations of high-sensitivity C-reactive protein in patients with metastatic colorectal cancer: results from the ITACa trial. AB - Serum levels of C-reactive protein are (CRP) higher in patients with neoplastic conditions and numerous studies have been performed to clarify the etiologic and prognostic role of the high-sensitivity CRP (hs-CRP) in cancer. Our study was conducted on patients enrolled in the prospective randomized "Italian Trial in Advanced Colorectal Cancer (ITACa)" to assess hs-CRP levels and their impact on overall survival (OS) and progression-free survival (PFS). Serum samples from 132 ITACa patients were collected at baseline and 2 months after starting first-line chemotherapy. The supernatant was immediately transferred to cryovials and stored at -80 degrees C. After thawing, hs-CRP was measured with the Cobas c501 analyzer. High levels of hs-CRP (>= 13.1 mg/L) were associated with poorer median PFS (p < 0.0001) and OS (p < 0.0001) than low hs-CRP levels (< 13.1 mg/L). hs-CRP values in 107 patients were evaluated again after 2 months of therapy, revealing that patients with low hs-CRP levels in both baseline and second serum samples had the best median PFS and OS. Our study confirms the prognostic value of hs-CRP in patients with metastatic colorectal carcinoma. PMID- 26848627 TI - Antifungal Quinoline Alkaloids from Waltheria indica. AB - Chemical investigation of a dichloromethane extract of the aerial parts of Waltheria indica led to the isolation and characterization of five polyhydroxymethoxyflavonoids, namely, oxyanin A (1), vitexicarpin (3), chrysosplenol E (4), flindulatin (5), 5-hydroxy-3,7,4'-trimethoxyflavone (6), and six quinolone alkaloids, waltheriones M-Q (2, 7, 8, 10, 11) and 5(R)-vanessine (9). Among these, compounds 2, 7, 8, 10, and 11 have not yet been described in the literature. Their chemical structures were established by means of spectroscopic data interpretation including (1)H and (13)C, HSQC, HMBC, COSY, and NOESY NMR experiments and UV, IR, and HRESIMS. The absolute configurations of the compounds were established by ECD. The isolated constituents and 10 additional quinoline alkaloids previously isolated from the roots of the plant were evaluated for their in vitro antifungal activity against the human fungal pathogen Candida albicans, and 10 compounds (7, 9, 11-16, 18, 21) showed growth inhibitory activity on both planktonic cells and biofilms (MIC <= 32 MUg/mL). Their spectrum of activity against other pathogenic Candida species and their cytotoxicity against human HeLa cells were also determined. In addition, the cytological effect of the antifungal isolated compounds on the ultrastructure of C. albicans was evaluated by transmission electron microscopy. PMID- 26848628 TI - Visual intraoperative estimation of cup and stem position is not reliable in minimally invasive hip arthroplasty. AB - Background and purpose - In hip arthroplasty, acetabular inclination and anteversion-and also femoral stem torsion-are generally assessed by eye intraoperatively. We assessed whether visual estimation of cup and stem position is reliable. Patients and methods - In the course of a subgroup analysis of a prospective clinical trial, 65 patients underwent cementless hip arthroplasty using a minimally invasive anterolateral approach in lateral decubitus position. Altogether, 4 experienced surgeons assessed cup position intraoperatively according to the operative definition by Murray in the anterior pelvic plane and stem torsion in relation to the femoral condylar plane. Inclination, anteversion, and stem torsion were measured blind postoperatively on 3D-CT and compared to intraoperative results. Results - The mean difference between the 3D-CT results and intraoperative estimations by eye was -4.9 degrees (-18 to 8.7) for inclination, 9.7 degrees (-16 to 41) for anteversion, and -7.3 degrees (-34 to 15) for stem torsion. We found an overestimation of > 5 degrees for cup inclination in 32 hips, an overestimation of > 5 degrees for stem torsion in 40 hips, and an underestimation < 5 degrees for cup anteversion in 42 hips. The level of professional experience and patient characteristics had no clinically relevant effect on the accuracy of estimation by eye. Altogether, 46 stems were located outside the native norm of 10-20 degrees as defined by Tonnis, measured on 3D-CT. Interpretation - Even an experienced surgeon's intraoperative estimation of cup and stem position by eye is not reliable compared to 3D-CT in minimally invasive THA. The use of mechanical insertion jigs, intraoperative fluoroscopy, or imageless navigation is recommended for correct implant insertion. PMID- 26848629 TI - Recovery Strategy and Mechanism of Aged Lithium Ion Batteries after Shallow Depth of Discharge at Elevated Temperature. AB - Performance degradation of prismatic lithium ion batteries (LIBs) with LiCoO2 and mesocarbon microbead as active materials is investigated at an elevated temperature for shallow depth of discharge. Aged LIBs are disassembled to characterize the interface morphology, bulk structure, and reversible capacity of an individual electrode. It is found that the formation of interfacial blocking layer (IBL) on the anode results in the cathode state of charge (SOC) offset, which is the primary reason for the cathode degradation. The main capacity degradation of the anode is attributed to the IBL on the anode surface that impedes the intercalation and deintercalation of lithium ions. Because the full battery capacity is limited by the cathode during aging, the cathode SOC offset is the most important reason for the full battery capacity loss. Interestingly, the capacity of aged LIBs can be recovered to a relative high level after adding the electrolyte, rather than the solvent. This recovery is attributed to the relief of the cathode SOC offset and the dissolution of the anode IBL, which reopens the intercalation and deintercalation paths of lithium ions on the anode. Moreover, it is revealed that the relief of cathode SOC offset and the dissolution of anode IBL trigger and promote mutually to drive the recovery of LIBs. PMID- 26848630 TI - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY 2016 OUTPATIENT GLUCOSE MONITORING CONSENSUS STATEMENT. AB - This document represents the official position of the American Association of Clinical Endocrinologists and American College of Endocrinology. Where there were no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician. PMID- 26848631 TI - AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON THYROID DYSFUNCTION CASE FINDING. AB - Hypothyroidism and hyperthyroidism can be readily diagnosed and can be treated in a safe, cost-effective manner. Professional organizations have given guidance on how and when to employ thyroid-stimulating hormone testing for the detection of thyroid dysfunction. Most recently, the United States Preventive Services Task Force did not endorse screening for thyroid dysfunction based on a lack of proven benefit and potential harm of treating those with thyroid dysfunction, which is mostly subclinical disease. The American Association of Clinical Endocrinologists (AACE) is concerned that this may discourage physicians from testing for thyroid dysfunction when clinically appropriate. Given the lack of specificity of thyroid associated symptoms, the appropriate diagnosis of thyroid disease requires biochemical confirmation. The Thyroid Scientific Committee of the AACE has produced this White Paper to highlight the important difference between screening and case-based testing in the practice of clinical medicine. We recommend that thyroid dysfunction should be frequently considered as a potential etiology for many of the nonspecific complaints that physicians face daily. The application and success of safe and effective interventions are dependent on an accurate diagnosis. We, therefore, advocate for an aggressive case-finding approach, based on identifying those persons most likely to have thyroid disease that will benefit from its treatment. PMID- 26848632 TI - ADJUNCT THERAPIES IN TYPE 1 DIABETES. PMID- 26848634 TI - High-Performance Pd3Pb Intermetallic Catalyst for Electrochemical Oxygen Reduction. AB - Extensive efforts to develop highly active and strongly durable electrocatalyst for oxygen reduction are motivated by a need for metal-air batteries and fuel cells. Here, we report a very promising catalyst prototype of structurally ordered Pd-based alloys, Pd3Pb intermetallic compound. Such structurally ordered Pd3Pb/C exhibits a significant increase in mass activity. More importantly, compared to the conventional Pt/C catalysts, ordered Pd3Pb/C is highly durable and exhibits a much longer cycle life and higher cell efficiency in Zn-air batteries. Interestingly, ordered Pd3Pb/C possesses very high methanol tolerance during electrochemical oxygen reduction, which make it an excellent methanol tolerant cathode catalyst for alkaline polymer electrolyte membrane fuel cells. This study provides a promising route to optimize the synthesis of ordered Pd based intermetallic catalysts for fuel cells and metal-air batteries. PMID- 26848633 TI - Predictors of higher-risk chronic opioid prescriptions in an academic primary care setting. AB - BACKGROUND: Patients with chronic noncancer pain treated with higher doses of opioids or concurrent substance use are at increased risk of adverse events. Although several national guidelines recommend maximum dosing thresholds and urine drug testing, adherence to these guidelines is inconsistent. METHODS: To identify predictors of higher-risk opioid prescriptions in 2 academic primary care clinics, the authors developed a retrospective cohort of 842 patients who were prescribed >=5 opioid prescriptions for noncancer pain between March 2012 and March 2013. The authors evaluated odds of higher-dose opioid prescriptions and urine drug testing using multivariate logistic models. RESULTS: Among study subjects, 47% received prescriptions for the equivalent of >=50 mg morphine per day. After adjustment for confounders, patients with a resident primary care provider were less likely to receive higher-dose prescriptions compared with faculty providers (odds ratio = 0.66, 95% confidence interval [CI]: 0.46-0.94), whereas patients with a nonlocal home address were more likely to be prescribed higher doses (odds ratio = 2.1, 95% CI: 1.5-2.9). Hispanic, Asian, and older patients were also less likely to be prescribed higher doses. Urine drug testing was not regularly completed (35% over 2 years), but odds of testing were higher for patients who self-identified as black, had resident primary care providers, lived locally, or were prescribed higher opioid doses. CONCLUSIONS: In this academic clinical setting, patients with a resident primary care provider are less likely to receive higher-risk opioid prescriptions, as are Hispanic, Asian, and older patients. Black patients complete urine drug tests more frequently independent of other patient and provider characteristics. Additional studies are needed to assess why patients who travel larger distances to their primary care clinic are prescribed higher doses of opioids for chronic noncancer pain. PMID- 26848635 TI - New 3,4-seco-cycloartane triterpenes from Gardenia sootepensis. AB - Two new 3,4-seco-cycloartane triterpenes, named sootepins H (1) and I (2), were isolated from the ethyl acetate extract of the leaves and twigs of Gardenia sootepensis. Their structures were elucidated on the basis of 1D- and 2D-nuclear magnetic resonance (NMR) analysis, as well as high-resolution mass spectrometry (HR-MS), infrared (IR), and ultra violet (UV). PMID- 26848637 TI - The prevalence of binge eating disorder and its relationship to work and classroom productivity and activity impairment. AB - OBJECTIVE: The study aimed to determine the prevalence of binge eating disorder on university campus, its associations with health risk factors, and its associations with work and classroom productivity and activity impairment, adjusted for health risk factors. PARTICIPANTS: The study was conducted at a public midwestern university in the United States and involved 1,165 students. METHODS: Data were collected online, using preestablished instruments. Descriptive, chi-square, correlation, and robust multiple regression tests were used. RESULTS: About 7.8% of the participants were assessed as having binge eating disorder. Binge eating disorder was more common among obese students than nonobese students. Associations were found between moderate binge eating disorder and classroom productivity and daily activity impairment; however, sleep duration and physical activity were the strongest predictors. CONCLUSIONS: University students are at risk of binge eating disorder. Interventions with this population should include education, screening, and clinical consultation when warranted. PMID- 26848638 TI - Loss of Anticontractile Effect of Perivascular Adipose Tissue on Pregnant Rats: A Potential Role of Tumor Necrosis Factor-alpha. AB - The present investigation examined the effect of pregnancy on the anticontractile effect of perivascular adipose tissue (PVAT) on the rat. Ring segments of the aorta, with and without PVAT, were set up in organ baths for isometric tension recording. In both groups, concentration-response curves to 5-hydroxytryptamine (5-HT) were displaced to the right with a reduction of the maximum response in aorta segments with PVAT. The anticontractile effect of PVAT was attenuated on segments from pregnant rats. 4-Aminopyridine (4-AP), an inhibitor of voltage gated potassium (Kv) channels, enhanced 5-HT-induced contractions of aorta segments from pregnant and nonpregnant rats only when PVAT was attached. There was no difference in the effect of 4-aminopyridine on 5-HT-induced contractions of aorta segments with PVAT from pregnant and nonpregnant rats. There was also no significant difference in the expression of Kv7.4 channels in aorta segments (with PVAT) between pregnant and nonpregnant rats. Tumor necrosis factor-alpha (TNF-alpha) was detected in PVAT from pregnant and nonpregnant rats. The level of TNF-alpha was significantly greater in PVAT from pregnant rats. Treatment of pregnant rats with pentoxyphyline significantly reduced the level of TNF-alpha in the PVAT and restored the anticontractile effect of PVAT on aorta segments from pregnant rats. Finally, TNF-alpha (10 ng/mL) potentiated 5-HT-induced contractions of PVAT-containing pregnant rat aorta. These results would suggest that the loss of anticontractile effect of PVAT in pregnant rat aorta could be due to enhanced production of TNF-alpha in the PVAT in these rats. PMID- 26848639 TI - Reversible polyphenylacetylene helix conversion driven by a thermoresponsive rotaxane switch in the solid state. AB - The reversible helical pitch change of polyphenylacetylenes by a thermoresponsive rotaxane switch inserted into the side chain was demonstrated through an accompanying color change. Similar to an ethynyl rotaxane monomer, the corresponding polyphenylacetylene having a rotaxane moiety in its side chain exhibited a reversible helical pitch change induced by the thermoresponsive rotaxane switch, i.e., the amine/ammonium salt was converted by treatment with trichloroacetic acid (TCA) and subsequent heating, which led to thermal decomposition of TCA to chloroform and carbon dioxide. Such a rotaxane switch caused the helical pitch change and the accompanying color change of the polymer main chain in both solution and solid state. PMID- 26848640 TI - Clear Cell Atypical Fibroxanthoma: Clinicopathological Study of 6 Cases and Review of the Literature With Special Emphasis on the Differential Diagnosis. AB - Atypical fibroxanthoma (AFX) is an uncommon dermal-based neoplasm arising on the sun-damaged skin of elderly people. Clear cell AFX is a rare variant with only 12 cases reported until the present date, all of them as case reports, except for 1 small series of 3 cases. The authors report 6 new cases and review the literature with special emphasis on the differential diagnosis. The clear cell variant represents 5% of AFX from their files. Histopathologically, it consists of sheets of epithelioid, pleomorphic cells, intermixed with a varying number of giant multinucleated and spindle cells, the latter arranged in a fascicular pattern. All cell types predominantly exhibit a clear, microvacuolated cytoplasm with well demarcated cell borders. The clinical and immunohistochemical features of this variant are similar to those of the classic type. Clear cell AFX must be differentiated from other cutaneous clear cell neoplasms, some of them with an aggressive clinical behavior, including clear cell melanoma, primary cutaneous and metastatic clear cell carcinomas, clear cell sarcoma, pleomorphic liposarcoma, tumor of perivascular epithelioid cells, and distinctive dermal clear cell mesenchymal neoplasm. The clinical presentation and immunohistochemical profile play a key role in the differential diagnosis. PMID- 26848644 TI - Perioperative Nurses' Work Experience With Robotic Surgery: A Focus Group Study. AB - The aim of this study was to explore the work experience of perioperative nurses involved in robotic surgery. A qualitative descriptive study was conducted. Participants were 15 nurses who had been on a robotic surgery team at one of five major university hospitals in Seoul, South Korea. Participants were one male and 14 female nurses (mean age, 31.33 [SD, 4.19] years; range, 25-41 years). Their experience as robotic surgery nurses ranged from 8 months to 6 years. Nurses' experiences with robotic surgery were categorized within four main themes: (1) constant checking on patients' safety and the robot's functions; (2) unexpected robotic machine errors or malfunctions; (3) feelings of burden in a robotic surgical team; and (4) need and desire for more information and education. This study showed that there are common concerns about patient safety and the possibility of emergencies related to robot system failure among nurses. Offering more support for nurses involved in robotic surgery should be a priority to empower them to play an extended role in robotic surgery. PMID- 26848645 TI - Utilizing Home Healthcare Electronic Health Records for Telehomecare Patients With Heart Failure: A Decision Tree Approach to Detect Associations With Rehospitalizations. AB - Heart failure is a complex condition with a significant impact on patients' lives. A few studies have identified risk factors associated with rehospitalization among telehomecare patients with heart failure using logistic regression or survival analysis models. To date, there are no published studies that have used data mining techniques to detect associations with rehospitalizations among telehomecare patients with heart failure. This study is a secondary analysis of the home healthcare electronic medical record called the Outcome and Assessment Information Set-C for 552 telemonitored heart failure patients. Bivariate analyses using SAS and a decision tree technique using Waikato Environment for Knowledge Analysis were used. From the decision tree technique, the presence of skin issues was identified as the top predictor of rehospitalization that could be identified during the start of care assessment, followed by patient's living situation, patient's overall health status, severe pain experiences, frequency of activity-limiting pain, and total number of anticipated therapy visits combined. Examining risk factors for rehospitalization from the Outcome and Assessment Information Set-C database using a decision tree approach among a cohort of telehomecare patients provided a broad understanding of the characteristics of patients who are appropriate for the use of telehomecare or who need additional supports. PMID- 26848646 TI - A competitive coordination-based CeO2 nanowire-DNA nanosensor: fast and selective detection of hydrogen peroxide in living cells and in vivo. AB - A competitive coordination-based hydrogen peroxide (H2O2) nanosensor is constructed by the assembly of FAM-tagged single-strand (ss) DNA on cerium oxide nanowires (CeO2 NWs). This fluorescent nanosensor is capable of rapidly and selectively tracking H2O2 within living cells, as well as directly visualizing H2O2 generated by wound-induced oxidative damage in zebrafish larvae. PMID- 26848648 TI - Recent Development of Plasmonic Resonance-Based Photocatalysis and Photovoltaics for Solar Utilization. AB - Increasing utilization of solar energy is an effective strategy to tackle our energy and energy-related environmental issues. Both solar photocatalysis (PC) and solar photovoltaics (PV) have high potential to develop technologies of many practical applications. Substantial research efforts are devoted to enhancing visible light activation of the photoelectrocatalytic reactions by various modifications of nanostructured semiconductors. This review paper emphasizes the recent advancement in material modifications by means of the promising localized surface plasmonic resonance (LSPR) mechanisms. The principles of LSPR and its effects on the photonic efficiency of PV and PC are discussed here. Many research findings reveal the promise of Au and Ag plasmonic nanoparticles (NPs). Continual investigation for increasing the stability of the plasmonic NPs will be fruitful. PMID- 26848649 TI - Elicitation, an Effective Strategy for the Biotechnological Production of Bioactive High-Added Value Compounds in Plant Cell Factories. AB - Plant in vitro cultures represent an attractive and cost-effective alternative to classical approaches to plant secondary metabolite (PSM) production (the "Plant Cell Factory" concept). Among other advantages, they constitute the only sustainable and eco-friendly system to obtain complex chemical structures biosynthesized by rare or endangered plant species that resist domestication. For successful results, the biotechnological production of PSM requires an optimized system, for which elicitation has proved one of the most effective strategies. In plant cell cultures, an elicitor can be defined as a compound introduced in small concentrations to a living system to promote the biosynthesis of the target metabolite. Traditionally, elicitors have been classified in two types, abiotic or biotic, according to their chemical nature and exogenous or endogenous origin, and notably include yeast extract, methyl jasmonate, salicylic acid, vanadyl sulphate and chitosan. In this review, we summarize the enhancing effects of elicitors on the production of high-added value plant compounds such as taxanes, ginsenosides, aryltetralin lignans and other types of polyphenols, focusing particularly on the use of a new generation of elicitors such as coronatine and cyclodextrins. PMID- 26848650 TI - Transcriptome-Wide Identification and Expression Profiling Analysis of Chrysanthemum Trihelix Transcription Factors. AB - Trihelix transcription factors are thought to feature a typical DNA-binding trihelix (helix-loop-helix-loop-helix) domain that binds specifically to the GT motif, a light-responsive DNA element. Members of the trihelix family are known to function in a number of processes in plants. Here, we characterize 20 trihelix family genes in the important ornamental plant chrysanthemum (Chrysanthemum morifolium). Based on transcriptomic data, 20 distinct sequences distributed across four of five groups revealed by a phylogenetic tree were isolated and amplified. The phylogenetic analysis also identified four pairs of orthologous proteins shared by Arabidopsis and chrysanthemum and five pairs of paralogous proteins in chrysanthemum. Conserved motifs in the trihelix proteins shared by Arabidopsis and chrysanthemum were analyzed using MEME, and further bioinformatic analysis revealed that 16 CmTHs can be targeted by 20 miRNA families and that miR414 can target 9 CmTHs. qPCR results displayed that most chrysanthemum trihelix genes were highly expressed in inflorescences, while 20 CmTH genes were in response to phytohormone treatments and abiotic stresses. This work improves our understanding of the various functions of trihelix gene family members in response to hormonal stimuli and stress. PMID- 26848652 TI - Radical-Mediated Enzymatic Polymerizations. AB - Polymerization reactions are commonly effected by exposing monomer formulations to some initiation stimulus such as elevated temperature, light, or a chemical reactant. Increasingly, these polymerization reactions are mediated by enzymes- catalytic proteins--owing to their reaction efficiency under mild conditions as well as their environmental friendliness. The utilization of enzymes, particularly oxidases and peroxidases, for generating radicals via reduction oxidation mechanisms is especially common for initiating radical-mediated polymerization reactions, including vinyl chain-growth polymerization, atom transfer radical polymerization, thiol-ene step-growth polymerization, and polymerization via oxidative coupling. While enzyme-mediated polymerization is useful for the production of materials intended for subsequent use, it is especially well-suited for in situ polymerizations, where the polymer is formed in the place where it will be utilized. Such polymerizations are especially useful for biomedical adhesives and for sensing applications. PMID- 26848651 TI - Methods to Design and Synthesize Antibody-Drug Conjugates (ADCs). AB - Antibody-drug conjugates (ADCs) have become a promising targeted therapy strategy that combines the specificity, favorable pharmacokinetics and biodistributions of antibodies with the destructive potential of highly potent drugs. One of the biggest challenges in the development of ADCs is the application of suitable linkers for conjugating drugs to antibodies. Recently, the design and synthesis of linkers are making great progress. In this review, we present the methods that are currently used to synthesize antibody-drug conjugates by using thiols, amines, alcohols, aldehydes and azides. PMID- 26848653 TI - Apobec-1 Complementation Factor (A1CF) Inhibits Epithelial-Mesenchymal Transition and Migration of Normal Rat Kidney Proximal Tubular Epithelial Cells. AB - Apobec-1 complementation factor (A1CF) is a member of the heterogeneous nuclear ribonucleoproteins (hnRNP) family, which participates in site-specific posttranscriptional RNA editing of apolipoprotein B (apoB) transcript. The posttranscriptional editing of apoB mRNA by A1CF in the small intestine is required for lipid absorption. Apart from the intestine, A1CF mRNA is also reported to be highly expressed in the kidneys. However, it is remained unknown about the functions of A1CF in the kidneys. The aim of this paper is to explore the potential functions of A1CF in the kidneys. Our results demonstrated that in C57BL/6 mice A1CF was weakly expressed in embryonic kidneys from E15.5dpc while strongly expressed in mature kidneys after birth, and it mainly existed in the tubules of inner cortex. More importantly, we identified A1CF negatively regulated the process of epithelial-mesenchymal transition (EMT) in kidney tubular epithelial cells. Our results found ectopic expression of A1CF up regulated the epithelial markers E-cadherin, and down-regulated the mesenchymal markers vimentin and alpha-smooth muscle actin (alpha-SMA) in NRK52e cells. In addition, knockdown of A1CF enhanced EMT contrary to the overexpression effect. Notably, the two A1CF variants led to the similar trend in the EMT process. Taken together, these data suggest that A1CF may be an antagonistic factor to the EMT process of kidney tubular epithelial cells. PMID- 26848656 TI - Addition of Adipose-Derived Stem Cells to Mesenchymal Stem Cell Sheets Improves Bone Formation at an Ectopic Site. AB - To determine the effect of adipose-derived stem cells (ADSCs) added to bone marrow-derived mesenchymal stem cell (MSC) sheets on bone formation at an ectopic site. We isolated MSCs and ADSCs from the same rabbits. We then prepared MSC sheets for implantation with or without ADSCs subcutaneously in the backs of severe combined immunodeficiency (SCID) mice. We assessed bone formation at eight weeks after implantation by micro-computed tomography and histological analysis. In osteogenic medium, MSCs grew to form multilayer sheets containing many calcium nodules. MSC sheets without ADSCs formed bone-like tissue; although neo-bone and cartilage-like tissues were sparse and unevenly distributed by eight weeks after implantation. In comparison, MSC sheets with ADSCs promoted better bone regeneration as evidenced by the greater density of bone, increased mineral deposition, obvious formation of blood vessels, large number of interconnected ossified trabeculae and woven bone structures, and greater bone volume/total volume within the composite constructs. Our results indicate that although sheets of only MSCs have the potential to form tissue engineered bone at an ectopic site, the addition of ADSCs can significantly increase the osteogenic potential of MSC sheets. Thus, the combination of MSC sheets with ADSCs may be regarded as a promising therapeutic strategy to stimulate bone regeneration. PMID- 26848655 TI - Effects of Atorvastatin Dose and Concomitant Use of Angiotensin-Converting Enzyme Inhibitors on Renal Function Changes over Time in Patients with Stable Coronary Artery Disease: A Prospective Observational Study. AB - Angiotensin-converting enzyme inhibitors (ACEI) and statins are widely used in patients with coronary artery disease (CAD). Our aim was to compare changes in glomerular filtration rate (GFR) over time in subjects with stable CAD according to atorvastatin dose and concomitant use of ACEI. We studied 78 men with stable CAD referred for an elective coronary angiography who attained the then-current guideline-recommended target level of low-density lipoproteins (LDL) cholesterol below 2.5 mmol/L in a routine fasting lipid panel on admission and were receiving atorvastatin at a daily dose of 10-40 mg for >=3 months preceding the index hospitalization. Due to an observational study design, atorvastatin dosage was not intentionally modified for other reasons. GFR was estimated during index hospitalization and at about one year after discharge from our center. Irrespective of ACEI use, a prevention of kidney function loss was observed only in those treated with the highest atorvastatin dose. In 38 subjects on ACEI, both of the higher atorvastatin doses were associated with increasing beneficial effects on GFR changes (mean +/- SEM: -4.2 +/- 2.4, 1.1 +/- 1.6, 5.2 +/- 2.4 mL/min per 1.73 m2 for the 10-mg, 20-mg and 40-mg atorvastatin group, respectively, p = 0.02 by ANOVA; Spearman's rho = 0.50, p = 0.001 for trend). In sharp contrast, in 40 patients without ACEI, no significant trend effect was observed across increasing atorvastatin dosage (respective GFR changes: -1.3 +/- 1.0, -4.7 +/- 2.1, 4.8 +/- 3.6 mL/min per 1.73 m2, p = 0.02 by ANOVA; rho = 0.08, p = 0.6 for trend). The results were substantially unchanged after adjustment for baseline GFR or time-dependent variations of LDL cholesterol. Thus, concomitant ACEI use appears to facilitate the ability of increasing atorvastatin doses to beneficially modulate time-dependent changes in GFR in men with stable CAD. PMID- 26848654 TI - Molecular Pathological Classification of Neurodegenerative Diseases: Turning towards Precision Medicine. AB - Neurodegenerative diseases (NDDs) are characterized by selective dysfunction and loss of neurons associated with pathologically altered proteins that deposit in the human brain but also in peripheral organs. These proteins and their biochemical modifications can be potentially targeted for therapy or used as biomarkers. Despite a plethora of modifications demonstrated for different neurodegeneration-related proteins, such as amyloid-beta, prion protein, tau, alpha-synuclein, TAR DNA-binding protein 43 (TDP-43), or fused in sarcoma protein (FUS), molecular classification of NDDs relies on detailed morphological evaluation of protein deposits, their distribution in the brain, and their correlation to clinical symptoms together with specific genetic alterations. A further facet of the neuropathology-based classification is the fact that many protein deposits show a hierarchical involvement of brain regions. This has been shown for Alzheimer and Parkinson disease and some forms of tauopathies and TDP 43 proteinopathies. The present paper aims to summarize current molecular classification of NDDs, focusing on the most relevant biochemical and morphological aspects. Since the combination of proteinopathies is frequent, definition of novel clusters of patients with NDDs needs to be considered in the era of precision medicine. Optimally, neuropathological categorizing of NDDs should be translated into in vivo detectable biomarkers to support better prediction of prognosis and stratification of patients for therapy trials. PMID- 26848658 TI - Molecular Mechanisms of Nickel Allergy. AB - Allergic contact hypersensitivity to metals is a delayed-type allergy. Although various metals are known to produce an allergic reaction, nickel is the most frequent cause of metal allergy. Researchers have attempted to elucidate the mechanisms of metal allergy using animal models and human patients. Here, the immunological and molecular mechanisms of metal allergy are described based on the findings of previous studies, including those that were recently published. In addition, the adsorption and excretion of various metals, in particular nickel, is discussed to further understand the pathogenesis of metal allergy. PMID- 26848657 TI - Role of Epigenetics in Stem Cell Proliferation and Differentiation: Implications for Treating Neurodegenerative Diseases. AB - The main objectives of this review are to survey the current literature on the role of epigenetics in determining the fate of stem cells and to assess how this information can be used to enhance the treatment strategies for some neurodegenerative disorders, like Huntington's disease, Parkinson's disease and Alzheimer's disease. Some of these epigenetic mechanisms include DNA methylation and histone modifications, which have a direct impact on the way that genes are expressed in stem cells and how they drive these cells into a mature lineage. Understanding how the stem cells are behaving and giving rise to mature cells can be used to inform researchers on effective ways to design stem cell-based treatments. In this review article, the way in which the basic understanding of how manipulating this process can be utilized to treat certain neurological diseases will be presented. Different genetic factors and their epigenetic changes during reprogramming of stem cells into induced pluripotent stem cells (iPSCs) have significant potential for enhancing the efficacy of cell replacement therapies. PMID- 26848659 TI - Isolation and Characterization of a Novel Dicistrovirus Associated with Moralities of the Great Freshwater Prawn, Macrobrachium rosenbergii. AB - The giant freshwater prawn, Macrobrachium rosenbergii, is an economically important crustacean and is farmed in many countries. Since 2009, a larval mortality syndrome of M. rosenbergii has broken out and spread widely in the main breeding area, including Zhejiang, Jiangsu, Guangxi, and Guangdong Provinces in mainland China. A novel virus, named Macrobrachium rosenbergii Taihu virus (MrTV), was isolated from the moribund larvae and was determined to be the causative agent of the M. rosenbergii larval mortality syndrome by experimental infection. Further genomic sequencing suggested that the MrTV genome is monopartite, 10,303 nt in length, and dicistronic with two non-overlapping open reading frames (ORFs) separated by an intergenic region (IGR) and flanked by untranslated regions (UTRs). Phylogenetic analysis using the full-length genomic sequence and the putative amino acid sequences of the capsid protein revealed that MrTV was more closely related to the taura syndrome virus (TSV) than to any other viruses. According to these molecular features, we proposed that MrTV is a new species in the genus Aparavirus, family Dicistroviridae. These results may shed light on controlling larval mortality syndrome in M. rosenbergii. PMID- 26848660 TI - Integrated Gas Sensing System of SWCNT and Cellulose Polymer Concentrator for Benzene, Toluene, and Xylenes. AB - An integrated cellulose polymer concentrator/single-walled carbon nanotube (SWCNT) sensing system is demonstrated to detect benzene, toluene, and xylenes (BTX) vapors. The sensing system consists of functionalized cellulose as a selective concentrator disposed directly on top of a conductive SWCNT sensing layer. Functionalized cellulose concentrator (top layer) selectively adsorbs the target analyte and delivers the concentrated analyte as near as possible to the SWCNT sensing layer (bottom layer), which enables the simultaneous concentrating and sensing within a few seconds. The selectivity can be achieved by functionalizing cellulose acetate with a pentafluorophenylacetyl selector that interacts strongly with the target BTX analytes. A new design of the integrated cellulose concentrator/SWCNT sensing system allows high sensitivity with limits of detection for benzene, toluene, and m-xylene vapors of 55 ppm, 19 ppm, and 14 ppm, respectively, selectivity, and fast responses (<10 s to reach equilibrium), exhibiting the potential ability for on-site, real-time sensing applications. The sensing mechanism involves the selective adsorption of analytes in the concentrator film, which in turn mediates changes in the electronic potentials at the polymer-SWCNT interface and potentially changes in the tunneling barriers between nanotubes. PMID- 26848661 TI - Theoretical Basis and Application for Measuring Pork Loin Drip Loss Using Microwave Spectroscopy. AB - During cutting and processing of meat, the loss of water is critical in determining both product quality and value. From the point of slaughter until packaging, water is lost due to the hanging, movement, handling, and cutting of the carcass, with every 1% of lost water having the potential to cost a large meat processing plant somewhere in the region of ?50,000 per day. Currently the options for monitoring the loss of water from meat, or determining its drip loss, are limited to destructive tests which take 24-72 h to complete. This paper presents results from work which has led to the development of a novel microwave cavity sensor capable of providing an indication of drip loss within 6 min, while demonstrating good correlation with the well-known EZ-Driploss method (R2 = 0.896). PMID- 26848662 TI - Evaluation of Empirical Tropospheric Models Using Satellite-Tracking Tropospheric Wet Delays with Water Vapor Radiometer at Tongji, China. AB - An empirical tropospheric delay model, together with a mapping function, is commonly used to correct the tropospheric errors in global navigation satellite system (GNSS) processing. As is well-known, the accuracy of tropospheric delay models relies mainly on the correction efficiency for tropospheric wet delays. In this paper, we evaluate the accuracy of three tropospheric delay models, together with five mapping functions in wet delays calculation. The evaluations are conducted by comparing their slant wet delays with those measured by water vapor radiometer based on its satellite-tracking function (collected data with large liquid water path is removed). For all 15 combinations of three tropospheric models and five mapping functions, their accuracies as a function of elevation are statistically analyzed by using nine-day data in two scenarios, with and without meteorological data. The results show that (1) no matter with or without meteorological data, there is no practical difference between mapping functions, i.e., Chao, Ifadis, Vienna Mapping Function 1 (VMF1), Niell Mapping Function (NMF), and MTT Mapping Function (MTT); (2) without meteorological data, the UNB3 is much better than Saastamoinen and Hopfield models, while the Saastamoinen model performed slightly better than the Hopfield model; (3) with meteorological data, the accuracies of all three tropospheric delay models are improved to be comparable, especially for lower elevations. In addition, the kinematic precise point positioning where no parameter is set up for tropospheric delay modification is conducted to further evaluate the performance of tropospheric delay models in positioning accuracy. It is shown that the UNB3 model is best and can achieve about 10 cm accuracy for the N and E coordinate component while 20 cm accuracy for the U coordinate component no matter the meteorological data is available or not. This accuracy can be obtained by the Saastamoinen model only when meteorological data is available, and degraded to 46 cm for the U component if the meteorological data is not available. PMID- 26848663 TI - Pressure and Temperature Sensors Using Two Spin Crossover Materials. AB - The possibility of a new design concept for dual spin crossover based sensors for concomitant detection of both temperature and pressure is presented. It is conjectured from numerical results obtained by mean field approximation applied to a Ising-like model that using two different spin crossover compounds containing switching molecules with weak elastic interactions it is possible to simultaneously measure P and T. When the interaction parameters are optimized, the spin transition is gradual and for each spin crossover compounds, both temperature and pressure values being identified from their optical densities. This concept offers great perspectives for smart sensing devices. PMID- 26848664 TI - From Data Acquisition to Data Fusion: A Comprehensive Review and a Roadmap for the Identification of Activities of Daily Living Using Mobile Devices. AB - This paper focuses on the research on the state of the art for sensor fusion techniques, applied to the sensors embedded in mobile devices, as a means to help identify the mobile device user's daily activities. Sensor data fusion techniques are used to consolidate the data collected from several sensors, increasing the reliability of the algorithms for the identification of the different activities. However, mobile devices have several constraints, e.g., low memory, low battery life and low processing power, and some data fusion techniques are not suited to this scenario. The main purpose of this paper is to present an overview of the state of the art to identify examples of sensor data fusion techniques that can be applied to the sensors available in mobile devices aiming to identify activities of daily living (ADLs). PMID- 26848665 TI - Simultaneous-Fault Diagnosis of Gearboxes Using Probabilistic Committee Machine. AB - This study combines signal de-noising, feature extraction, two pairwise-coupled relevance vector machines (PCRVMs) and particle swarm optimization (PSO) for parameter optimization to form an intelligent diagnostic framework for gearbox fault detection. Firstly, the noises of sensor signals are de-noised by using the wavelet threshold method to lower the noise level. Then, the Hilbert-Huang transform (HHT) and energy pattern calculation are applied to extract the fault features from de-noised signals. After that, an eleven-dimension vector, which consists of the energies of nine intrinsic mode functions (IMFs), maximum value of HHT marginal spectrum and its corresponding frequency component, is obtained to represent the features of each gearbox fault. The two PCRVMs serve as two different fault detection committee members, and they are trained by using vibration and sound signals, respectively. The individual diagnostic result from each committee member is then combined by applying a new probabilistic ensemble method, which can improve the overall diagnostic accuracy and increase the number of detectable faults as compared to individual classifiers acting alone. The effectiveness of the proposed framework is experimentally verified by using test cases. The experimental results show the proposed framework is superior to existing single classifiers in terms of diagnostic accuracies for both single- and simultaneous-faults in the gearbox. PMID- 26848667 TI - From Punishment to Treatment: The "Clinical Alternative to Punitive Segregation" (CAPS) Program in New York City Jails. AB - The proliferation of jails and prisons as places of institutionalization for persons with serious mental illness (SMI) has resulted in many of these patients receiving jail-based punishments, including solitary confinement. Starting in 2013, the New York City (NYC) jail system developed a new treatment unit for persons with SMI who were judged to have violated jail rules (and previously would have been punished with solitary confinement) called the Clinical Alternative to Punitive Segregation (CAPS) unit. CAPS is designed to offer a full range of therapeutic activities and interventions for these patients, including individual and group therapy, art therapy, medication counseling and community meetings. Each CAPS unit requires approximately $1.5 million more investment per year, largely in additional staff as compared to existing mental health units, and can house approximately 30 patients. Patients with less serious mental illness who received infractions were housed on units that combined solitary confinement with some clinical programming, called Restrictive Housing Units (RHU). Between 1 December 2013 and 31 March 2015, a total of 195 and 1433 patients passed through the CAPS and RHU units, respectively. A small cohort of patients experienced both CAPS and RHU (n = 90). For these patients, their rates of self-harm and injury were significantly lower while on the CAPS unit than when on the RHU units. Improvements in clinical outcomes are possible for incarcerated patients with mental illness with investment in new alternatives to solitary confinement. We have started to adapt the CAPS approach to existing mental health units as a means to promote better clinical outcomes and also help prevent jail based infractions. The cost of these programs and the dramatic differences in length of stay for patients who earn these jail-based infractions highlight the need for alternatives to incarceration, some of which have recently been announced in NYC. PMID- 26848666 TI - Fucoidan as a Potential Therapeutic for Major Blinding Diseases--A Hypothesis. AB - Fucoidan is a heterogeneous group of sulfated polysaccharide with a high content of l-fucose, which can be extracted from brown algae and marine invertebrates. It has many beneficial biological activities that make fucoidan an interesting candidate for therapeutic application in a variety of diseases. Age-related macular degeneration and diabetic retinopathy are major causes for vision loss and blindness in the industrialized countries and increasingly in the developing world. Some of the characteristics found in certain fucoidans, such as its anti oxidant activity, complement inhibition or interaction with the Vascular Endothelial Growth factor, which would be of high interest for a potential application of fucoidan in age-related macular degeneration or diabetic retinopathy. However, the possible usage of fucoidan in ophthalmological diseases has received little attention so far. In this review, biological activities of fucoidan that could be of interest regarding these diseases will be discussed. PMID- 26848669 TI - Spatial Modelling Tools to Integrate Public Health and Environmental Science, Illustrated with Infectious Cryptosporidiosis. AB - Contemporary spatial modelling tools can help examine how environmental exposures such as climate and land use together with socio-economic factors sustain infectious disease transmission in humans. Spatial methods can account for interactions across global and local scales, geographic clustering and continuity of the exposure surface, key characteristics of many environmental influences. Using cryptosporidiosis as an example, this review illustrates how, in resource rich settings, spatial tools have been used to inform targeted intervention strategies and forecast future disease risk with scenarios of environmental change. When used in conjunction with molecular studies, they have helped determine location-specific infection sources and environmental transmission pathways. There is considerable scope for such methods to be used to identify data/infrastructure gaps and establish a baseline of disease burden in resource limited settings. Spatial methods can help integrate public health and environmental science by identifying the linkages between the physical and socio economic environment and health outcomes. Understanding the environmental and social context for disease spread is important for assessing the public health implications of projected environmental change. PMID- 26848670 TI - Impact of Geographic Location on Vitamin D Status and Bone Mineral Density. AB - A significant decline of serum 25-hydroxyvitamin D concentration [25(OH)D] with increasing latitude has been reported only for Caucasians. To determine the association between serum 25(OH)D and geographic location and its impact on bone mineral density (BMD) in an Asian population, a total of 17,508 subjects (8910 men and 8598 women) from the 2008-2010 Korea National Health and Nutrition Examination Survey (KNHANES) were stratified into four age groups and analyzed for 25(OH)D and BMD according to geographic location (South, 33 degrees N-35 degrees N; Middle, 36 degrees N; North, 37 degrees N-38 degrees N). Mean 25(OH)D were 47.7 and 41.2 nmol/L; calcium intake, 564.9 & 442.3 mg/d; femoral neck BMD, 0.829 & 0.721 g/cm2; and lumbar spine BMD, 0.960 & 0.918 g/cm2 for men and women, respectively. Both men and women living in the South had significantly higher 25(OH)D and femoral neck BMD for those >=50 years old. Lumbar spine BMD was significantly higher in men >=50 years old, and for women 10-29 & 50-69 years old living in the South. A 1 or 2 degree difference in latitude has a significant effect on serum 25(OH)D and BMD in this low vitamin D status population. Thus, consideration of geographic location for a recommendation of vitamin D intake may be necessary. PMID- 26848668 TI - Environmental Chemical Assessment in Clinical Practice: Unveiling the Elephant in the Room. AB - A growing body of evidence suggests chemicals present in air, water, soil, food, building materials and household products are toxicants that contribute to the many chronic diseases typically seen in routine medical practice. Yet, despite calls from numerous organisations to provide clinicians with more training and awareness in environmental health, there are multiple barriers to the clinical assessment of toxic environmental exposures. Recent developments in the fields of systems biology, innovative breakthroughs in biomedical research encompassing the "-omics" fields, and advances in mobile sensing, peer-to-peer networks and big data, provide tools that future clinicians can use to assess environmental chemical exposures in their patients. There is also a need for concerted action at all levels, including actions by individual patients, clinicians, medical educators, regulators, government and non-government organisations, corporations and the wider civil society, to understand the "exposome" and minimise the extent of toxic exposures on current and future generations. Clinical environmental chemical risk assessment may provide a bridge between multiple disciplines that uses new technologies to herald in a new era in personalised medicine that unites clinicians, patients and civil society in the quest to understand and master the links between the environment and human health. PMID- 26848671 TI - The Relationship between AMH and AMHR2 Polymorphisms and the Follicular Phase in Late Reproductive Stage Women. AB - The objective of this work was the analysis of the relationships between the genotypes of the AMH and AMH receptor type 2 genes, hormone levels and the menstrual cycle in a group of Polish women in the late reproductive stage. The study was conducted using a measurement-based method (body weight and height), laboratory method (serum hormone levels AMH, FSH and E2), and genetic analysis (DNA isolated from whole blood by a salting-out method). The study involved 345 healthy, late-reproductive-stage women from Poland, aged 42.3 +/- 4.5 years. The analysis demonstrated that neither the T/T and G/T+G/G genotypes of the AMH Ile(49)Ser polymorphism (rs10407022), nor the A/A and the G/A + G/G genotypes of the AMHR2 2482 A > G polymorphism (rs2002555), nor the C/C and C/T + T/T genotypes of the AMH polymorphism (rs11170547) were statistically significantly related (p > 0.05) to such factors as age, BMI, hormone (FSH and E2) levels and ovarian parameters (AMH) in the follicular phase. No relationships were found between ovarian parameters (FSH, E2, AMH) and genetic variants of AMH (rs10407022) and AMHR2 (rs11170547, rs2002555) in healthy women in the late reproductive stage. PMID- 26848672 TI - Mapping to Support Fine Scale Epidemiological Cholera Investigations: A Case Study of Spatial Video in Haiti. AB - The cartographic challenge in many developing world environments suffering a high disease burden is a lack of granular environmental covariates suitable for modeling disease outcomes. As a result, epidemiological questions, such as how disease diffuses at intra urban scales are extremely difficult to answer. This paper presents a novel geospatial methodology, spatial video, which can be used to collect and map environmental covariates, while also supporting field epidemiology. An example of epidemic cholera in a coastal town of Haiti is used to illustrate the potential of this new method. Water risks from a 2012 spatial video collection are used to guide a 2014 survey, which concurrently included the collection of water samples, two of which resulted in positive lab results "of interest" (bacteriophage specific for clinical cholera strains) to the current cholera situation. By overlaying sample sites on 2012 water risk maps, a further fifteen proposed water sample locations are suggested. These resulted in a third spatial video survey and an additional "of interest" positive water sample. A potential spatial connection between the "of interest" water samples is suggested. The paper concludes with how spatial video can be an integral part of future fine-scale epidemiological investigations for different pathogens. PMID- 26848673 TI - Climate Justice in Rural Southeastern United States: A Review of Climate Change Impacts and Effects on Human Health. AB - Climate justice is a local, national, and global movement to protect at-risk populations who are disproportionately affected by climate change. The social context for this review is the Southeastern region of the United States, which is particularly susceptible to climate change because of the geography of the area and the vulnerabilities of the inhabiting populations. Negative human health effects on variable and vulnerable populations within the Southeast region due to changing climate are concerning, as health threats are not expected to produce parallel effects among all individuals. Vulnerable communities, such as communities of color, indigenous people, the geographically isolated, and those who are socioeconomically disadvantaged and already experiencing poor environmental quality, are least able to respond and adapt to climate change. Focusing on vulnerable populations in the Southeastern United States, this review is a synthesis of the recent (2010 to 2015) literature-base on the health effects connected to climate change. This review also addresses local and regional mitigation and adaptation strategies for citizens and leaders to combat direct and indirect human health effects related to a changing climate. PMID- 26848674 TI - Residential Proximity to Major Roadways and Lung Cancer Mortality. Italy, 1990 2010: An Observational Study. AB - BACKGROUND: Air pollution from road traffic has been associated to an increased risk of lung cancer. Herein, we investigated the association between lung cancer mortality and residence near Italian highways or national major roads. METHODS: Information on deaths for lung cancer registered from 1990 to 2010 and stratified by age, gender, and urban or rural municipality of residence at death were obtained from the National Institute of Statistics. Distance between the centroid of the municipality of residence and closest major roadways was considered as a proxy of pollution exposure. Relative Risks (RR) and 95% confidence intervals (CI) were computed using Poisson log-linear models adjusted for age, calendar period, deprivation index, North/South gradient, and urban/rural status. RESULTS: A gradient in risk for lung cancer mortality was seen for residents within 50 meters (m) of national major roads. In particular, in rural municipalities a statistically significant increased risk for lung cancer death was observed in both sexes (RR = 1.27 for distance <25 m vs. 500-1999 m, 95% CI 1.17-1.42, in men; RR = 1.97, 95% CI 1.64-2.39, in women). In urban municipalities, weak risks of borderline significance were documented in both sexes (RR = 1.06, 95% CI 0.99 1.15 in men; and RR = 1.09, 95% CI 0.97-1.22 in women). No statistically significant association emerged between residence within 100 to 500 m from highways and RRs of death for lung cancer. CONCLUSIONS: In Italy, residing near national major roads, in particular in rural municipalities, was related to elevated risks of death for lung cancer. PMID- 26848675 TI - Impacts of Climatic Variability on Vibrio parahaemolyticus Outbreaks in Taiwan. AB - This study aimed to investigate and quantify the relationship between climate variation and incidence of Vibrio parahaemolyticus in Taiwan. Specifically, seasonal autoregressive integrated moving average (ARIMA) models (including autoregression, seasonality, and a lag-time effect) were employed to predict the role of climatic factors (including temperature, rainfall, relative humidity, ocean temperature and ocean salinity) on the incidence of V. parahaemolyticus in Taiwan between 2000 and 2011. The results indicated that average temperature (+), ocean temperature (+), ocean salinity of 6 months ago (+), maximum daily rainfall (current (-) and one month ago (-)), and average relative humidity (current and 9 months ago (-)) had significant impacts on the incidence of V. parahaemolyticus. Our findings offer a novel view of the quantitative relationship between climate change and food poisoning by V. parahaemolyticus in Taiwan. An early warning system based on climate change information for the disease control management is required in future. PMID- 26848676 TI - Effects of the Residential Environment on Health in Japan Linked with Travel Behavior. AB - This paper aims to clarify how the residential environment is associated with overall health-related quality of life (QOL) via active travel (walking and cycling), by reflecting the influence of different trip purposes in Japan. The health-related QOL includes physical, mental, and social dimensions. For this study we implemented a questionnaire survey in 20 cities in Japan in 2010 and obtained valid answers from 1202 respondents. The residential environment is defined in terms of distances to and densities of different daily facilities extracted from both the survey and external GIS data. We found that the effects of residential environment on active travel behavior are mixed and limited, depending on types of trip makers. Unexpectedly, travel behavior has no direct effects on the health-related QOL. The residential environment, which is only observed indirectly via lifestyle habits for commuters, has limited effects on health. As for noncommuters, neither their travel behavior nor the residential environment influences their health-related QOL. PMID- 26848677 TI - The Role of HBZ in HTLV-1-Induced Oncogenesis. AB - Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia (ATL) and chronic inflammatory diseases. HTLV-1 bZIP factor (HBZ) is transcribed as an antisense transcript of the HTLV-1 provirus. Among the HTLV-1-encoded viral genes, HBZ is the only gene that is constitutively expressed in all ATL cases. Recent studies have demonstrated that HBZ plays an essential role in oncogenesis by regulating viral transcription and modulating multiple host factors, as well as cellular signaling pathways, that contribute to the development and continued growth of cancer. In this article, I summarize the current knowledge of the oncogenic function of HBZ in cell proliferation, apoptosis, T-cell differentiation, immune escape, and HTLV-1 pathogenesis. PMID- 26848678 TI - Metagenomic Analysis of Virioplankton of the Subtropical Jiulong River Estuary, China. AB - Viruses are the most abundant biological entities in the oceans, and encompass a significant reservoir of genetic diversity. However, little is known about their biodiversity in estuary environments, which represent a highly dynamic and potentially more diverse habitat. Here, we report a metagenomic analysis of the dsDNA viral community from the Jiulong River Estuary (JRE), China, and provide a comparative analysis with other closely related environments. The results showed that the majority of JRE virome did not show any significant similarity to the database. For the major viral group (Caudovirales) detected in the sample, Podoviridae (44.88%) were the most abundant family, followed by Siphoviridae (32.98%) and Myoviridae (17.32%). The two most abundant viruses identified in the virome were phages HTVC010P and HMO-2011, which infect bacteria belonging to marine SAR11 and SAR116 clades, respectively. Two contigs larger than 20 kb, which show similar overall genome architectures to Celeribacter phage P12053L and Thalosomonas phage BA3, respectively, were generated during assembly. Comparative analysis showed that the JRE virome was more similar to marine viromes than to freshwater viromes, and shared a relative coarse-grain genetic overlap (averaging 14.14% +/- 1.68%) with other coastal viromes. Our study indicated that the diversity and community structure of the virioplankton found in JRE were mainly affected by marine waters, with less influence from freshwater discharge. PMID- 26848679 TI - Begomovirus-Associated Satellite DNA Diversity Captured Through Vector-Enabled Metagenomic (VEM) Surveys Using Whiteflies (Aleyrodidae). AB - Monopartite begomoviruses (Geminiviridae), which are whitefly-transmitted single stranded DNA viruses known for causing devastating crop diseases, are often associated with satellite DNAs. Since begomovirus acquisition or exchange of satellite DNAs may lead to adaptation to new plant hosts and emergence of new disease complexes, it is important to investigate the diversity and distribution of these molecules. This study reports begomovirus-associated satellite DNAs identified during a vector-enabled metagenomic (VEM) survey of begomoviruses using whiteflies collected in various locations (California (USA), Guatemala, Israel, Puerto Rico, and Spain). Protein-encoding satellite DNAs, including alphasatellites and betasatellites, were identified in Israel, Puerto Rico, and Guatemala. Novel alphasatellites were detected in samples from Guatemala and Puerto Rico, resulting in the description of a phylogenetic clade (DNA-3-type alphasatellites) dominated by New World sequences. In addition, a diversity of small (~640-750 nucleotides) satellite DNAs similar to satellites associated with begomoviruses infecting Ipomoea spp. were detected in Puerto Rico and Spain. A third class of satellite molecules, named gammasatellites, is proposed to encompass the increasing number of reported small (<1 kilobase), non-coding begomovirus-associated satellite DNAs. This VEM-based survey indicates that, although recently recovered begomovirus genomes are variations of known genetic themes, satellite DNAs hold unexplored genetic diversity. PMID- 26848680 TI - Adenovirus E1A/E1B Transformed Amniotic Fluid Cells Support Human Cytomegalovirus Replication. AB - The human cytomegalovirus (HCMV) replicates to high titers in primary human fibroblast cell cultures. A variety of primary human cells and some tumor-derived cell lines do also support permissive HCMV replication, yet at low levels. Cell lines established by transfection of the transforming functions of adenoviruses have been notoriously resistant to HCMV replication and progeny production. Here, we provide first-time evidence that a permanent cell line immortalized by adenovirus type 5 E1A and E1B (CAP) is supporting the full HCMV replication cycle and is releasing infectious progeny. The CAP cell line had previously been established from amniotic fluid cells which were likely derived from membranes of the developing fetus. These cells can be grown under serum-free conditions. HCMV efficiently penetrated CAP cells, expressed its immediate-early proteins and dispersed restrictive PML-bodies. Viral DNA replication was initiated and viral progeny became detectable by electron microscopy in CAP cells. Furthermore, infectious virus was released from CAP cells, yet to lower levels compared to fibroblasts. Subviral dense bodies were also secreted from CAP cells. The results show that E1A/E1B expression in transformed cells is not generally repressive to HCMV replication and that CAP cells may be a good substrate for dense body based vaccine production. PMID- 26848681 TI - Pandemic Influenza A (H1N1) Virus Infection Increases Apoptosis and HIV-1 Replication in HIV-1 Infected Jurkat Cells. AB - Influenza virus infection has a significant impact on public health, since it is a major cause of morbidity and mortality. It is not well-known whether influenza virus infection affects cell death and human immunodeficiency virus (HIV)-1 replication in HIV-1-infected patients. Using a lymphoma cell line, Jurkat, we examined the in vitro effects of pandemic influenza A (H1N1) virus (pH1N1) infection on cell death and HIV-1 RNA production in infected cells. We found that pH1N1 infection increased apoptotic cell death through Fas and Bax-mediated pathways in HIV-1-infected Jurkat cells. Infection with pH1N1 virus could promote HIV-1 RNA production by activating host transcription factors including nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB), nuclear factor of activated T-cells (NFAT) and activator protein 1 (AP-1) through mitogen-activated protein kinases (MAPK) pathways and T-cell antigen receptor (TCR)-related pathways. The replication of HIV-1 latent infection could be reactivated by pH1N1 infection through TCR and apoptotic pathways. These data indicate that HIV-1 replication can be activated by pH1N1 virus in HIV-1-infected cells resulting in induction of cell death through apoptotic pathways. PMID- 26848683 TI - Mother-to-Child Transmission of HTLV-1 Epidemiological Aspects, Mechanisms and Determinants of Mother-to-Child Transmission. AB - Human T-cell Lymphotropic Virus type 1 (HTLV-1) is a human retrovirus that infects at least 5-10 million people worldwide, and is the etiological agent of a lymphoproliferative malignancy; Adult T-cell Leukemia/Lymphoma (ATLL); and a chronic neuromyelopathy, HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), as well as other inflammatory diseases such as infective dermatitis and uveitis. Besides sexual intercourse and intravenous transmission, HTLV-1 can also be transmitted from infected mother to child during prolonged breastfeeding. Some characteristics that are linked to mother-to-child transmission (MTCT) of HTLV-1, such as the role of proviral load, antibody titer of the infected mother, and duration of breastfeeding, have been elucidated; however, most of the mechanisms underlying HTLV-1 transmission during breast feeding remain largely unknown, such as the sites of infection and cellular targets as well as the role of milk factors. The present review focuses on the latest findings and current opinions and perspectives on MTCT of HTLV-1. PMID- 26848684 TI - A Potential of an Anti-HTLV-I gp46 Neutralizing Monoclonal Antibody (LAT-27) for Passive Immunization against Both Horizontal and Mother-to-Child Vertical Infection with Human T Cell Leukemia Virus Type-I. AB - Although the number of human T-cell leukemia virus type-I (HTLV-I)-infected individuals in the world has been estimated at over 10 million, no prophylaxis vaccines against HTLV-I infection are available. In this study, we took a new approach for establishing the basis of protective vaccines against HTLV-I. We show here the potential of a passively administered HTLV-I neutralizing monoclonal antibody of rat origin (LAT-27) that recognizes epitopes consisting of the HTLV-I gp46 amino acids 191-196. LAT-27 completely blocked HTLV-I infection in vitro at a minimum concentration of 5 MUg/mL. Neonatal rats born to mother rats pre-infused with LAT-27 were shown to have acquired a large quantity of LAT 27, and these newborns showed complete resistance against intraperitoneal infection with HTLV-I. On the other hand, when humanized immunodeficient mice were pre-infused intravenously with humanized LAT-27 (hu-LAT-27), all the mice completely resisted HTLV-I infection. These results indicate that hu-LAT-27 may have a potential for passive immunization against both horizontal and mother-to child vertical infection with HTLV-I. PMID- 26848682 TI - Genetic Markers of the Host in Persons Living with HTLV-1, HIV and HCV Infections. AB - Human T-cell leukemia virus type 1 (HTLV-1), hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are prevalent worldwide, and share similar means of transmission. These infections may influence each other in evolution and outcome, including cancer or immunodeficiency. Many studies have reported the influence of genetic markers on the host immune response against different persistent viral infections, such as HTLV-1 infection, pointing to the importance of the individual genetic background on their outcomes. However, despite recent advances on the knowledge of the pathogenesis of HTLV-1 infection, gaps in the understanding of the role of the individual genetic background on the progress to disease clinically manifested still remain. In this scenario, much less is known regarding the influence of genetic factors in the context of dual or triple infections or their influence on the underlying mechanisms that lead to outcomes that differ from those observed in monoinfection. This review describes the main factors involved in the virus-host balance, especially for some particular human leukocyte antigen (HLA) haplotypes, and other important genetic markers in the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other persistent viruses, such as HIV and HCV. PMID- 26848685 TI - Iodine Status of Women of Reproductive Age in Sierra Leone and Its Association with Household Coverage with Adequately Iodized Salt. AB - Salt iodization programs are a public health success in tackling iodine deficiency. Yet, a large proportion of the world's population remains at risk for iodine deficiency. In a nationally representative cross-sectional survey in Sierra Leone, household salt samples and women's urine samples were quantitatively analyzed for iodine content. Salt was collected from 1123 households, and urine samples from 817 non-pregnant and 154 pregnant women. Household coverage with adequately iodized salt (>=15 mg/kg iodine) was 80.7%. The median urinary iodine concentration (UIC) of pregnant women was 175.8 ug/L and of non-pregnant women 190.8 ug/L. Women living in households with adequately iodized salt had higher median UIC (for pregnant women: 180.6 ug/L vs. 100.8 ug/L, respectively, p < 0.05; and for non-pregnant women: 211.3 ug/L vs. 97.8 ug/L, p < 0.001). Differences in UIC by residence, region, household wealth, and women's education were much smaller in women living in households with adequately iodized salt than in households without. Despite the high household coverage of iodized salt in Sierra Leone, it is important to reach the 20% of households not consuming adequately iodized salt. Salt iodization has the potential for increasing equity in iodine status even with the persistence of other risk factors for deficiency. PMID- 26848686 TI - Structure-Activity Relationship of Chlorotoxin-Like Peptides. AB - Animal venom (e.g., scorpion) is a rich source of various protein and peptide toxins with diverse physio-/pharmaco-logical activities, which generally exert their action via target-specific modulation of different ion channel functions. Scorpion venoms are among the most widely-known source of peptidyl neurotoxins used for callipering different ion channels, such as; Na+, K+, Ca+, Cl(-), etc. A new peptide of the chlorotoxin family (i.e., Bs-Tx7) has been isolated, sequenced and synthesized from scorpion Buthus sindicus (family Buthidae) venom. This peptide demonstrates 66% with chlorotoxin (ClTx) and 82% with CFTR channel inhibitor (GaTx1) sequence identities reported from Leiurus quinquestriatus hebraeus venom. The toxin has a molecular mass of 3821 Da and possesses four intra-chain disulphide bonds. Amino acid sequence analysis of Bs-Tx7 revealed the presence of a scissile peptide bond (i.e., Gly-Ile) for human MMP2, whose activity is increased in the case of tumour malignancy. The effect of hMMP2 on Bs Tx7, or vice versa, observed using the FRET peptide substrate with methoxycoumarin (Mca)/dinitrophenyl (Dnp) as fluorophore/quencher, designed and synthesized to obtain the lowest Km value for this substrate, showed approximately a 60% increase in the activity of hMMP2 upon incubation of Bs-Tx7 with the enzyme at a micromolar concentration (4 uM), indicating the importance of this toxin in diseases associated with decreased MMP2 activity. PMID- 26848687 TI - Diminished but Not Abolished Effect of Two His351 Mutants of Anthrax Edema Factor in a Murine Model. AB - Edema toxin (ET), which is composed of a potent adenylate cyclase (AC), edema factor (EF), and protective antigen (PA), is one of the major toxicity factors of Bacillus anthracis. In this study, we introduced mutations in full-length EF to generate alanine EF(H351A) and arginine EF(H351R) variants. In vitro activity analysis displayed that the adenylyl cyclase activity of both the mutants was significantly diminished compared with the wild-type EF. When the native and mutant toxins were administered subcutaneously in a mouse footpad edema model, severe acute swelling was evoked by wild-type ET, while the symptoms induced by mutant toxins were very minor. Systemic administration of these EF variants caused non-lethal hepatotoxicity. In addition, EF(H351R) exhibited slightly higher activity in causing more severe edema than EF(H351A). Our findings demonstrate that the toxicity of ET is not abolished by substitution of EF residue His351 by alanine or arginine. These results also indicate the potential of the mouse footpad edema model as a sensitive method for evaluating both ET toxicity and the efficacy of candidate therapeutic agents. PMID- 26848688 TI - Conditional Melanoma Cancer Survival in the United States. AB - Beyond relative survival, which indicates the likelihood that patients will not die from causes associated with their cancer, conditional relative survival probabilities provide further useful prognostic information to cancer patients, tailored to the time already survived from diagnosis. This study presents conditional relative survival for melanoma patients in the United States, diagnosed during 2000-2008 and followed through 2012. Analyses are based on 62,803 male and 50,261 female cases in population-based cancer registries in the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute. Five-year relative survival estimates are presented for melanoma patients who have already survived one, two, three, four, or five years after the initial diagnosis. Five- and ten-year relative survival decreases with age, stage at diagnosis, and is lower among males, Blacks, and Hispanics. Five-year conditional relative survival improves with each year already survived. The potential for improvement in five-year conditional relative survival is greatest for older age, males, Blacks, Hispanics, and in later staged cases. For local disease, five-year conditional relative survival was significantly lower in ages greater than 65 years and in Blacks. It was significantly higher in females, non Hispanics, and married individuals. Age had a greater inverse relationship with five-year survival in later staged disease. A similar result occurred for females and married individuals. In contrast, non-Hispanics had better five-year survival if diagnosed with local or regional disease, but not distant disease. PMID- 26848689 TI - Titan as the Abode of Life. AB - Titan is the only world we know, other than Earth, that has a liquid on its surface. It also has a thick atmosphere composed of nitrogen and methane with a thick organic haze. There are lakes, rain, and clouds of methane and ethane. Here, we address the question of carbon-based life living in Titan liquids. Photochemically produced organics, particularly acetylene, in Titan's atmosphere could be a source of biological energy when reacted with atmospheric hydrogen. Light levels on the surface of Titan are more than adequate for photosynthesis, but the biochemical limitations due to the few elements available in the environment may lead only to simple ecosystems that only consume atmospheric nutrients. Life on Titan may make use of the trace metals and other inorganic elements produced by meteorites as they ablate in its atmosphere. It is conceivable that H2O molecules on Titan could be used in a biochemistry that is rooted in hydrogen bonds in a way that metals are used in enzymes by life on Earth. Previous theoretical work has shown possible membrane structures, azotosomes, in Titan liquids, azotosomes, composed of small organic nitrogen compounds, such as acrylonitrile. The search for a plausible information molecule for life in Titan liquids remains an open research topic-polyethers have been considered and shown to be insoluble at Titan temperatures. Possible search strategies for life on Titan include looking for unusual concentrations of certain molecules reflecting biological selection. Homochirality is a special and powerful example of such biology selection. Environmentally, a depletion of hydrogen in the lower atmosphere may be a sign of metabolism. A discovery of life in liquid methane and ethane would be our first compelling indication that the universe is full of diverse and wondrous life forms. PMID- 26848690 TI - Integrated Pest Management of Coffee Berry Borer: Strategies from Latin America that Could Be Useful for Coffee Farmers in Hawaii. AB - The coffee berry borer (CBB), Hypothenemus hampei Ferrari (Coleoptera: Curculionidae: Scolytinae) is the primary arthropod pest of coffee plantations worldwide. Since its detection in Hawaii (September 2010), coffee growers are facing financial losses due to reduced quality of coffee yields. Several control strategies that include cultural practices, biological control agents (parasitoids), chemical and microbial insecticides (entomopathogenic fungi), and a range of post-harvest sanitation practices have been conducted to manage CBB around the world. In addition, sampling methods including the use of alcohol based traps for monitoring CBB populations have been implemented in some coffee producing countries in Latin America. It is currently unclear which combination of CBB control strategies is optimal under economical, environmental, and sociocultural conditions of Hawaii. This review discusses components of an integrated pest management program for CBB. We focus on practical approaches to provide guidance to coffee farmers in Hawaii. Experiences of integrated pest management (IPM) of CBB learned from Latin America over the past 25 years may be relevant for establishing strategies of control that may fit under Hawaiian coffee farmers' conditions. PMID- 26848691 TI - The Impact of Landscape Complexity on Invertebrate Diversity in Edges and Fields in an Agricultural Area. AB - Invertebrate diversity is important for a multitude of ecosystem services and as a component of the larger ecological food web. A better understanding of the factors influencing invertebrate taxonomic richness and diversity at both local and landscape scales is important for conserving biodiversity within the agricultural landscape. The aim of this study was to determine if invertebrate richness and diversity in agricultural field interiors and edges in central Illinois, USA, were related to the complexity of the surrounding landscape. Our results show taxonomic richness and diversity in field edges is positively related to large scale landscape complexity, but the relationship is negative for field interiors. These unexpected results need further study. PMID- 26848692 TI - Genetic Variations in Vesicoureteral Reflux Sequelae. AB - Urinary tract infections (UTI) are a common condition in children. Vesicoureteral reflux (VUR) represents a common associated condition with childhood UTI. UTI susceptibility appears to have a genetic component based on family and UTI cohort studies. Targeted analysis of innate immune system genetic variations indicate that these variations are important in UTI susceptibility. In this overview, we discuss how current cohorts and genetic strategies can be implemented to discover new susceptibility loci in patients with UTI. PMID- 26848693 TI - Assessing Activity and Location of Individual Laying Hens in Large Groups Using Modern Technology. AB - Tracking individual animals within large groups is increasingly possible, offering an exciting opportunity to researchers. Whereas previously only relatively indistinguishable groups of individual animals could be observed and combined into pen level data, we can now focus on individual actors within these large groups and track their activities across time and space with minimal intervention and disturbance. The development is particularly relevant to the poultry industry as, due to a shift away from battery cages, flock sizes are increasingly becoming larger and environments more complex. Many efforts have been made to track individual bird behavior and activity in large groups using a variety of methodologies with variable success. Of the technologies in use, each has associated benefits and detriments, which can make the approach more or less suitable for certain environments and experiments. Within this article, we have divided several tracking systems that are currently available into two major categories (radio frequency identification and radio signal strength) and review the strengths and weaknesses of each, as well as environments or conditions for which they may be most suitable. We also describe related topics including types of analysis for the data and concerns with selecting focal birds. PMID- 26848694 TI - Dogs on the Move: Factors Impacting Animal Shelter and Rescue Organizations' Decisions to Accept Dogs from Distant Locations. AB - Long-distance dog transfer programs are a topic of burgeoning interest in the animal welfare community, but little research has focused on such programs. This exploratory study, which surveyed 193 individuals associated with animal shelter and rescue organizations in the United States, evaluated factors that impacted organizations' decisions to transfer in dogs over long distances (>100 miles) and assessed what criteria were commonly valued by destination organizations. Specifically, we examined the following aspects of long-distance transfer programs: (1) logistics of long-distance dog transfers; (2) factors impacting dog selection; (3) medical requirements; (4) partnerships formed between source and destination organizations; and (5) perceptions of long-distance dog transfer programs by individuals affiliated with the destination organizations. This study revealed that many logistical considerations factor into transfer decisions and the formation of healthy partnerships between source and destination organizations. Participants indicated their organization's willingness to receive dogs of various sizes, coat colors and ages, but organizations often had restrictions regarding the breeds they would accept. Study findings indicate some organizations have strict quarantine policies and pre-transfer medical requirements, while others have no such requirements. PMID- 26848696 TI - Aspects of Mathematical Modelling of Pressure Retarded Osmosis. AB - In power generating terms, a pressure retarded osmosis (PRO) energy generating plant, on a river entering a sea or ocean, is equivalent to a hydroelectric dam with a height of about 60 meters. Therefore, PRO can add significantly to existing renewable power generation capacity if economical constrains of the method are resolved. PRO energy generation relies on a semipermeable membrane that is permeable to water and impermeable to salt. Mathematical modelling plays an important part in understanding flows of water and salt near and across semipermeable membranes and helps to optimize PRO energy generation. Therefore, the modelling can help realizing PRO energy generation potential. In this work, a few aspects of mathematical modelling of the PRO process are reviewed and discussed. PMID- 26848695 TI - Assay of Antioxidant Potential of Two Filamentous Fungi Isolated from the Indonesian Fermented Dried Cassava. AB - The antioxidant capacity and antioxidant constituents of two filamentous fungi (Acremonium charticola and Rhizopus oryzae) isolated from the Indonesian fermented dried cassava (gathot) were evaluated in the present study. The antioxidant capacity of the fungal crude extracts was assessed based on the 2,2' azino-bis(3-ethyl-benzthiazolin-6-sulfonicacid) (ABTS) method. Total phenolics were determined based on the Folin-Ciocalteu method, while the flavonoids content in the fungal extracts was determined by the spectrophotometric method with aluminum chloride. Total tannins were estimated by the Folin-Denis method. The ABTS+ radical scavenging activity was higher (p < 0.01) in A. charticola compared to that in R. oryzae and ascorbic acid (as a control). A higher (p < 0.01) content of total phenolics was detected in A. charticola than that in R. oryzae. Total flavonoids were higher (p < 0.01) in R. oryzae as compared with that in A. charticola. The fungus A. charticola had a higher (p < 0.01) level of total tannins than R. oryzae. In conclusion, both filamentous fungi isolated from the Indonesian fermented dried cassava exhibited antioxidant potentials as indicated by their capabilities to scavenge ABTS+. A. charticola had a higher antioxidant capacity than R. oryzae. The antioxidant capacity of A. charticola was attributed mainly to its phenolics and tannins contents. PMID- 26848698 TI - Protein Kinase D Enzymes as Regulators of EMT and Cancer Cell Invasion. AB - The Protein Kinase D (PKD) isoforms PKD1, PKD2, and PKD3 are effectors of the novel Protein Kinase Cs (nPKCs) and diacylglycerol (DAG). PKDs impact diverse biological processes like protein transport, cell migration, proliferation, epithelial to mesenchymal transition (EMT) and apoptosis. PKDs however, have distinct effects on these functions. While PKD1 blocks EMT and cell migration, PKD2 and PKD3 tend to drive both processes. Given the importance of EMT and cell migration to the initiation and progression of various malignancies, abnormal expression of PKDs has been reported in multiple types of cancers, including breast, pancreatic and prostate cancer. In this review, we discuss how EMT and cell migration are regulated by PKD isoforms and the significance of this regulation in the context of cancer development. PMID- 26848699 TI - Role of the Slug Transcription Factor in Chemically-Induced Skin Cancer. AB - The Slug transcription factor plays an important role in ultraviolet radiation (UVR)-induced skin carcinogenesis, particularly in the epithelial-mesenchymal transition (EMT) occurring during tumor progression. In the present studies, we investigated the role of Slug in two-stage chemical skin carcinogenesis. Slug and the related transcription factor Snail were expressed at high levels in skin tumors induced by 7,12-dimethylbenz[alpha]anthracene application followed by 12-O tetradecanoylphorbol-13-acetate (TPA) treatment. TPA-induced transient elevation of Slug and Snail proteins in normal mouse epidermis and studies in Slug transgenic mice indicated that Slug modulates TPA-induced epidermal hyperplasia and cutaneous inflammation. Although Snail family factors have been linked to inflammation via interactions with the cyclooxygenase-2 (COX-2) pathway, a pathway that also plays an important role in skin carcinogenesis, transient TPA induction of Slug and Snail appeared unrelated to COX-2 expression. In cultured human keratinocytes, TPA induced Snail mRNA expression while suppressing Slug expression, and this differential regulation was due specifically to activation of the TPA receptor. These studies show that Slug and Snail exhibit similar patterns of expression during both UVR and chemical skin carcinogenesis, that Slug and Snail can be differentially regulated under some conditions and that in vitro findings may not recapitulate in vivo results. PMID- 26848700 TI - Developing Biosensors in Developing Countries: South Africa as a Case Study. AB - A mini-review of the reported biosensor research occurring in South Africa evidences a strong emphasis on electrochemical sensor research, guided by the opportunities this transduction platform holds for low-cost and robust sensing of numerous targets. Many of the reported publications centre on fundamental research into the signal transduction method, using model biorecognition elements, in line with international trends. Other research in this field is spread across several areas including: the application of nanotechnology; the identification and validation of biomarkers; development and testing of biorecognition agents (antibodies and aptamers) and design of electro-catalysts, most notably metallophthalocyanine. Biosensor targets commonly featured were pesticides and metals. Areas of regional import to sub-Saharan Africa, such as HIV/AIDs and tuberculosis diagnosis, are also apparent in a review of the available literature. Irrespective of the targets, the challenge to the effective deployment of such sensors remains shaped by social and economic realities such that the requirements thereof are for low-cost and universally easy to operate devices for field settings. While it is difficult to disentangle the intertwined roles of national policy, grant funding availability and, certainly, of global trends in shaping areas of emphasis in research, most notable is the strong role that nanotechnology, and to a certain extent biotechnology, plays in research regarding biosensor construction. Stronger emphasis on collaboration between scientists in theoretical modelling, nanomaterials application and or relevant stakeholders in the specific field (e.g., food or health monitoring) and researchers in biosensor design may help evolve focused research efforts towards development and deployment of low-cost biosensors. PMID- 26848697 TI - Using Caenorhabditis elegans to Uncover Conserved Functions of Omega-3 and Omega 6 Fatty Acids. AB - The nematode Caenorhabditis elegans is a powerful model organism to study functions of polyunsaturated fatty acids. The ability to alter fatty acid composition with genetic manipulation and dietary supplementation permits the dissection of the roles of omega-3 and omega-6 fatty acids in many biological process including reproduction, aging and neurobiology. Studies in C. elegans to date have mostly identified overlapping functions of 20-carbon omega-6 and omega 3 fatty acids in reproduction and in neurons, however, specific roles for either omega-3 or omega-6 fatty acids are beginning to emerge. Recent findings with importance to human health include the identification of a conserved Cox independent prostaglandin synthesis pathway, critical functions for cytochrome P450 derivatives of polyunsaturated fatty acids, the requirements for omega-6 and omega-3 fatty acids in sensory neurons, and the importance of fatty acid desaturation for long lifespan. Furthermore, the ability of C. elegans to interconvert omega-6 to omega-3 fatty acids using the FAT-1 omega-3 desaturase has been exploited in mammalian studies and biotechnology approaches to generate mammals capable of exogenous generation of omega-3 fatty acids. PMID- 26848701 TI - Effects of Aqueous Extract of Phyllostachyos Caulis in Taeniam on Longitudinal Bone Growth in Adolescent Rats. AB - This study examined whether treatment with Phyllostachyos Caulis in Taeniam aqueous extract improves longitudinal bone growth in adolescent male rats. Three week-old male Sprague-Dawley rats were divided into three groups: a control group, a Phyllostachyos Caulis in Taeniam group (200 mg/kg, p.o.), and a recombinant human growth hormone group (20 ug/kg, s.c.). The total tibial length and the height of each growth plate zone were evaluated by radiography and histomorphometry. The total number of proliferative cells and 5-bromo-2' deoxyuridine-positive cells were counted after 5-bromo-2'-deoxyuridine staining. Serum total osteocalcin levels were assayed using an enzyme-linked immunosorbent assay. The average total tibial length of the Phyllostachyos Caulis in Taeniam group was significantly longer than that of the control group. The heights of the proliferative and hypertrophic zones in the Phyllostachyos Caulis in Taeniam group were increased, and the ratio of 5-bromo-2'-deoxyuridine-positive to total cells in the proliferative zone was also increased. The serum osteocalcin, growth hormone, and insulin-like growth factor-1 levels were significantly increased in the Phyllostachyos Caulis in Taeniam group compared to the control group. Insulin like growth factor-1 and insulin-like growth factor-1 receptor were highly expressed in the proliferative and hypertrophic zones in the Phyllostachyos Caulis in Taeniam group. The Phyllostachyos Caulis in Taeniam extract increased bone length, promoted cell proliferation, and activated the growth plate zones, which suggested that the extract could play an important role in longitudinal bone growth. Therefore, the Phyllostachyos Caulis in Taeniam extract might be a good alternative medicine to growth hormone therapy. PMID- 26848702 TI - Hypolipidemic Effects of Alkaloids from Rhizoma Coptidis in Diet-Induced Hyperlipidemic Hamsters. AB - This study was conducted to evaluate the antihyperlipidemic activity of five major alkaloids in Rhizoma Coptidis using high-fat- and high-cholesterol-induced hyperlipidemic hamsters. Hyperlipidemic hamsters were treated with coptisine, berberine, jatrorrhizine, palmatine, epiberberine, and total Rhizoma Coptidis alkaloids with a dose of 46.7 mg/kg * day for 140 days. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids were examined after alkaloid treatment. The results showed that all therapy agents prevented body weight gain, reduced the serum total cholesterol, and increased the high-density lipoprotein cholesterol of hamsters. Berberine, jatrorrhizine, and total Rhizoma Coptidis alkaloids decreased the triglyceride level in hyperlipidemic hamsters, while coptisine, jatrorrhizine, palmatine, and total Rhizoma Coptidis alkaloids significantly suppressed the elevation of the low-density lipoprotein cholesterol level. The fecal excretion of bile acids was significantly elevated by berberine, coptisine, jatrorrhizine, palmatine, total Rhizoma Coptidis alkaloids, and orlistat. Notably, total Rhizoma Coptidis alkaloids possess a much stronger lipid-lowering effect than the pure Rhizoma Coptidis alkaloids. Quantitative reverse transcription-polymerase chain reaction analyses revealed that Rhizoma Coptidis alkaloids could retard the synthesis of cholesterol by downregulating the mRNA expression of 3-hydroxy-3-methyl glutaryl coenzyme A reductase and accelerate the clearance of lipids by upregulating the low-density lipoprotein receptor, cholesterol 7alpha-hydroxylase, and uncoupling protein-2 expression. These findings highlight the critical role of Rhizoma Coptidis alkaloids in hyperlipidemia treatment. Thus, they need to be considered in future therapeutic approaches. PMID- 26848703 TI - Thymoquinone from Nigella sativa Seeds Promotes the Antitumor Activity of Noncytotoxic Doses of Topotecan in Human Colorectal Cancer Cells in Vitro. AB - Topotecan, a topoisomerase I inhibitor, is an anticancer drug widely used in the therapy of lung, ovarian, colorectal, and breast adenocarcinoma. Due to the primary dose-limiting toxicity of topotecan, which is myelosuppressive, it is necessary to identify other chemotherapeutic agents that can work synergistically with topotecan to increase its efficacy and limit its toxicity. Many studies have shown synergism upon the combination of topotecan with other chemotherapeutic agents such as gemcitabine. Other studies have demonstrated that pre-exposing cells to naturally occurring compounds such as thymoquinone, followed by gemcitabine or oxaliplatin, resulted in higher growth inhibition compared to treatment with gemcitabine or oxaliplatin alone. Our aim was to elucidate the underlying mechanism of action of topotecan in the survival and apoptotic pathways in human colon cancer cell lines in comparison to thymoquinone, to study the proapoptotic and antiproliferative effects of thymoquinone on the effectiveness of the chemotherapeutic agent topotecan, and to investigate the potential synergistic effect of thymoquinone with topotecan. Cells were incubated with different topotecan and thymoquinone concentrations for 24 and 48 hours in order to determine the IC50 for each drug. Combined therapy was then tested with +/- 2 values for the IC50 of each drug. The reduction in proliferation was significantly dose- and time-dependent. After determining the best combination (40 uM thymoquinone and 0.6 uM topotecan), cell proteins were extracted after treatment, and the expression levels of B-cell lymphoma 2 and of its associated X protein, proteins p53 and p21, and caspase-9, caspase-3, and caspase-8 were studied by Western blot. In addition, cell cycle analysis and annexin/propidium iodide staining were performed. Both drugs induced apoptosis through a p53 independent mechanism, whereas the expression of p21 was only seen in thymoquinone treatment. Cell cycle arrest in the S phase was detected with each compound separately, while combined treatment only increased the production of fragmented DNA. Both compounds induced apoptosis through the extrinsic pathway after 24 hours; however, after 48 hours, the intrinsic pathway was activated by topotecan treatment only. In conclusion, thymoquinone increased the effectiveness of the chemotherapeutic reagent topotecan by inhibiting proliferation and lowering toxicity through p53- and Bax/Bcl2-independent mechanisms. PMID- 26848704 TI - Secondary Metabolites from Endophytic Fungus Penicillium pinophilum Induce ROS Mediated Apoptosis through Mitochondrial Pathway in Pancreatic Cancer Cells. AB - The endophytic fungus strain MRCJ-326, isolated from Allium schoenoprasum, which is also known as Snow Mountain Garlic or Kashmiri garlic, was identified as Penicillium pinophilum on the basis of morphological characteristics and internal transcribed spacer region nucleotide sequence analysis. The endophytic fungus extract was subjected to 2D-SEPBOX bioactivity-guided fractionation and purification. The anthraquinone class of the bioactive secondary metabolites were isolated and characterized as oxyskyrin (1), skyrin (2), dicatenarin (3), and 1,6,8-trihydroxy-3-hydroxy methylanthraquinone (4) by spectral analysis. Dicatenarin and skyrin showed marked growth inhibition against the NCI60/ATCC panel of human cancer cell lines with least IC50 values of 12 ug/mL and 27 ug/mL, respectively, against the human pancreatic cancer (MIA PaCa-2) cell line. The phenolic hydroxyl group in anthraquinones plays a crucial role in the oxidative process and bioactivity. Mechanistically, these compounds, i.e., dicatenarin and skyrin, significantly induce apoptosis and transmit the apoptotic signal via intracellular reactive oxygen species generation, thereby inducing a change in the mitochondrial transmembrane potential and induction of the mitochondrial mediated apoptotic pathway. Our data indicated that dicatenarin and skyrin induce reactive oxygen species-mediated mitochondrial permeability transition and resulted in an increased induction of caspase-3 apoptotic proteins in human pancreatic cancer (MIA PaCa-2) cells. Dicatenarin showed a more pronounced cytotoxic/proapopotic effect than skyrin due to the presence of an additional phenolic hydroxyl group at C-4, which increases oxidative reactive oxygen species generation. This is the first report from P. pinophilum secreating these cytotoxic/proapoptotic secondary metabolites. PMID- 26848705 TI - Characterization of Neuraminidase Inhibitors in Korean Papaver rhoeas Bee Pollen Contributing to Anti-Influenza Activities In Vitro. AB - The active constituents of Korean Papaver rhoeas bee pollen conferring neuraminidase inhibitory activities (H1N1, H3N2, and H5N1) were investigated. Six flavonoids and one alkaloid were isolated and characterized by nuclear magnetic resonance and mass spectrometry data. These included kaempferol-3-sophoroside (1), kaempferol-3-neohesperidoside (2), kaempferol-3-sambubioside (3), kaempferol 3-glucoside (4), quercetin-3-sophoroside (5), luteolin (6), and chelianthifoline (7). All compounds showed neuraminidase inhibitory activities with IC50 values ranging from 10.7 to 151.1 uM. The most potent neuraminidase inhibitor was luteolin, which was the dominant content in the ethyl acetate fraction. All tested compounds displayed noncompetitive inhibition of H3N2 neuraminidase. Furthermore, compounds 1-7 all reduced the severity of virally induced cytopathic effects as determined by the Madin-Darby canine kidney cell-based assay showing antiviral activity with IC50 values ranging from 10.7 to 33.4 uM (zanamivir: 58.3 uM). The active compounds were quantified by high-performance liquid chromatography, and the total amount of compounds 1-7 made up about 0.592 g/100 g bee pollen, contributing a rich resource of a natural antiviral product. PMID- 26848706 TI - Cytotoxic Lignans and Sesquiterpenoids from the Rhizomes of Acorus tatarinowii. AB - Five new compounds, including a rare phenyldihydronaphthalene lignanamide (1), an unusual hybrid-norlignan derivative (2), a rare cycloheptenone oxide derivative (3), one new acorane-type sesquiterpenoid (4), and one new guaiane-type sesquiterpenoid (5), together with seven known compounds (6-12), have been isolated from the rhizomes of Acorus tatarinowii. The structures of compounds 1-5 were determined by means of extensive spectroscopic methods. To the best of our knowledge, this is first report of a phenyldihydronaphthalene lignanamide and hybrid-norlignan and cycloheptenone oxide derivatives from the genus Acorus. In addition, compound 5 represents the first guaiane-type sesquiterpenoid with an epoxy group located between C-6 and C-9 from natural sources. Compounds 1-12 were evaluated for their in vitro cytotoxicity against five tumor cell lines. Among them, 2, 3, 5, and 10 exhibited moderate cytotoxicity with IC50 values of 2.11 9.23 uM. PMID- 26848707 TI - Reproducibility of cervical cytopathology following an intervention by an external quality control laboratory. AB - BACKGROUND: This study assessed the effects of a continued education program on the agreement between cervical cytopathology exams interpreted by local laboratories and interpretation made by an external quality control laboratory (LabMEQ). METHODS: Overall, 9,798 exams were analyzed between 2007 and 2008, prior to implementation of a continued education program, and 10,028 between 2010 and 2011, following implementation. Continued education consisted of theoretical and practical classes held every two months. The chi-square test and the kappa coefficient were used in the statistical analysis. RESULTS: Following implementation of continued education, the rate of false-negative results, and those leading to delays in clinical management fell in eight laboratories and the rate of false-positive results in five. Agreement between the results reported by the laboratories and the findings of LabMEQ, evaluated according to clinical management, remained excellent in three laboratories (kappa >0.80 and <1.0), went from good (kappa >0.60 and <0.80) to excellent in seven and from excellent to good in two. Agreement regarding the identification of metaplastic epithelium was poor (kappa = 0.25) but progressed to excellent following the implementation of continued education (kappa = 0.950). Agreement between cytopathology results improved significantly following implementation of continued education in cases reported as unsatisfactory (P < 0.001), atypical squamous cells of undetermined significance, cannot exclude high-grade squamous intraepithelial lesion (P < 0.001), low-grade squamous intraepithelial lesion (P < 0.001), and glandular atypia (P < 0.001). CONCLUSION: Continued education contributed towards improving the reproducibility of cervical cytopathology, decreased the rates of false negative and false-positive results, and reduced delays in clinical management. PMID- 26848709 TI - Coffee consumption, smoking, and Parkinson's disease? The beneficial role of hydrogen sulfide. PMID- 26848708 TI - Altered Loyalties of Neuronal Markers in Cultured Slices of Resected Human Brain Tissue. AB - Organotypic cultures from normal neocortical tissue obtained at epilepsy surgery show a severe injury response. This response involves both neuronal degeneration and the proliferation of reactive cells. A salient feature of the reactive cells is the co-expression of microglial and astrocytic markers. Surprisingly, the reactive cells also began to express neuronal markers Tubulin betaIII and MAP2 adding to the confusion about their origin. Concomitant with their appearance in reactive cells MAP2 and Tubulin betaIII expression disappeared from neurons. While NeuN expression decreased significantly, it did not entirely disappear from many neurons. Moreover, it was not observed in reactive cells, showing that NeuN is a reliable marker of neurons. PMID- 26848711 TI - Morphological Engineering of CVD-Grown Transition Metal Dichalcogenides for Efficient Electrochemical Hydrogen Evolution. AB - 2D layered transition metal dichalcogenides (TMDCs) have emerged as new possibilites beyond conventional particulate catalysts in facilitating efficient electrochemical hydrogen evolution. This is mainly mediated by the ultrahigh surface-to-volume ratio and the effective coupling of all active sites with supporting electrodes. Especially, the facile chemical vapor deposition (CVD) method has enabled morphological engineering of monolayer TMDC catalysts toward development of abundant active edge sites within the 2D plane. Here, two pathways to achieve such purpose are highlighted, either by non-equilibrium growth of MoS2 dendrites or throughout high-density nucleation of MoS2 nanoflakes directly on the electrode materials. Furthermore, future research directions have also been proposed and discussed to further enhance the efficiency of such unique catalysts. PMID- 26848713 TI - Social well-being among adolescents and young adults with cancer: A systematic review. AB - BACKGROUND: A cancer diagnosis during adolescence or young adulthood may negatively influence social well-being. The existing literature concerning the social well-being of adolescents and young adults (AYAs) with cancer was reviewed to identify gaps in current research and highlight priority areas for future research. METHODS: A systematic review of the scientific literature published in English from 2000 through 2014 was performed. Eligible studies included patients and survivors diagnosed between the ages of 15 to 39 years that reported on social well-being domains in the City of Hope Cancer Survivor Quality of Life Model. Each article was reviewed for relevance using a standardized template. A total of 253 potential articles were identified. After exclusions, a final sample of 26 articles identified domains of social well-being that are believed to be understudied among AYAs with cancer: 1) educational attainment, employment, and financial burden; 2) social relationships; and 3) supportive care. Articles were read in their entirety, single coded, and summarized according to domain. RESULTS: AYAs with cancer report difficulties related to employment, educational attainment, and financial stability. They also report problems with the maintenance and development of peer and family relationships, intimate and marital relationships, and peer support. Supportive services are desired among AYAs. Few studies have reported results in reference to comparison samples or by cancer subtypes. CONCLUSIONS: Future research studies on AYAs with cancer should prioritize the inclusion of underserved AYA populations, more heterogeneous cancer samples, and comparison groups to inform the development of supportive services. Priority areas for potential intervention include education and employment reintegration, and social support networks. PMID- 26848712 TI - Non-genomic activities of retinoic acid receptor alpha control actin cytoskeletal events in human platelets. AB - Essentials Platelets employ proteins/signaling pathways traditionally thought reserved for nuclear niche. We determined retinoic-acid-receptor alpha (RARalpha) expression and function in human platelets. RARalpha/actin-related protein-2/3 complex (Arp2/3) interact via non-genomic signaling in platelets. RARalpha regulates Arp2/3-mediated actin cytoskeletal dynamics and platelet spreading. SUMMARY: Background Platelets utilize proteins and pathways classically reserved for the nuclear niche. Methods We determined whether human platelets express retinoic-acid-receptor family members, traditionally thought of as nuclear transcription factors, and deciphered the function of RARalpha. Results We found that RARalpha is robustly expressed in human platelets and megakaryocytes and interacts directly with actin-related protein-2/3 complex (Arp2/3) subunit 5 (Arp2/3s5). Arp2/3s5 co-localized with RARalpha in situ and regulated platelet cytoskeletal processes. The RARalpha ligand all-trans retinoic acid (atRA) disrupted RARalpha-Arp2/3 interactions. When isolated human platelets were treated with atRA, rapid cytoskeletal events (e.g. platelet spreading) were inhibited. In addition, when platelets were cultured for 18 h in the presence of atRA, actin-dependent morphological changes (e.g. extended cell body formation) were similarly inhibited. Using in vitro actin branching assays, RARalpha and Arp2/3-regulated complex actin branch formation was demonstrated. Consistent with inhibition of cytoskeletal processes in platelets, atRA, when added to this branching assay, resulted in dysregulated actin branching. Conclusion Our findings identify a previously unknown mechanism by which RARalpha regulates Arp2/3-mediated actin cytoskeletal dynamics through a non-genomic signaling pathway. These findings have broad implications in both nucleated and anucleate cells, where actin cytoskeletal events regulate cell morphology, movement and division. PMID- 26848715 TI - Patterns of Fetal Growth Based on Ultrasound Measurement and its Relationship with Small for Gestational Age at Birth in Rural Vietnam. AB - BACKGROUND: Small for gestational age (SGA) is a global health problem. Identifying the timing of fetal growth faltering is critical for developing preventive interventions. We aim to describe patterns of fetal growth and to predict SGA at birth using fetal ultrasound measurements. METHODS: We studied 1412 pregnant women enrolled in a randomised-controlled trial evaluating maternal micronutrient supplementation in Thai Nguyen province, Vietnam. Ultrasound examinations included biparietal diameter (BPD), head circumference (HC) and abdominal circumference (AC), and femur length (FL). Measures were assessed using the new international fetal growth standards (INTERGROWTH-21st Project). Generalised linear mixed logit regression models were used to examine the association between ultrasound measures and SGA at birth. RESULTS: Overall fetal growth restriction began in early pregnancy and continued through delivery, but the timing of growth faltering varied by measure: it began by 20 weeks for HC, BPD and AC, earlier as compared to FL growth that started >30 weeks. SGA infants had significantly lower mean fetal growth parameters as early as 14 weeks. Ultrasound measures below the 10th percentile were associated with a two to four times higher risk of SGA at birth compared to fetuses greater than the 50th percentile, with the largest odds ratios for AC (OR 3.9, 95% confidence interval (CI) 2.7, 5.7). CONCLUSIONS: Fetal growth faltering by ultrasound begins in early gestation among rural Vietnamese populations; these patterns clearly identified those to be born SGA. Efforts to prevent fetal growth faltering must begin early in pregnancy and perhaps even before pregnancy. PMID- 26848714 TI - Implications of the New US Cholesterol Guidelines in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). AB - BACKGROUND: The new US guidelines for the primary prevention of cardiovascular disease have substantially changed the approach to hyperlipidemia treatment. However, the impact of those recommendations in other populations is limited. In the present study, we evaluated the potential implications of those recommendations in the Brazilian population. HYPOTHESIS: The new U.S. recommendations may increase the proportion of individuals who are candidates for statin therapy. METHODS: We included all participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) without known cardiovascular disease. We calculated the indication for statin therapy according to the current Brazilian recommendations and the new US guidelines, using both the 5.0% and the 7.5% risk cutoffs to recommend treatment, and compared their impact in the Brazilian population stratified by age, sex, and race. RESULTS: Although the current guidelines would recommend treatment for 5499 (39.1%) individuals, the number of individuals eligible for statin therapy increased to 6014 (42.7%) and to 7130 (50.7%) using the 7.5% and 5% cutoffs, respectively (P < 0.001). This difference is more pronounced for older individuals, and virtually all individuals age >70 years would be eligible for statins, whereas the new guidelines would reduce the number of candidates for statin therapy in individuals age <45 years. CONCLUSIONS: The application of the new US guidelines for the use of lipid-lowering medications in a large middle-aged Brazilian cohort would result in a significant increase in the population eligible for statins. This is largely driven by males and older individuals. Additional cost effectiveness analyses are needed to define the appropriateness of this strategy in the Brazilian population. PMID- 26848716 TI - Relationships among multiple aspects of agriculture's environmental impact and productivity: a meta-analysis to guide sustainable agriculture. AB - Given the pressures on land to produce ever more food, doing it 'sustainably' is growing in importance. However, 'sustainable agriculture' is complex to define, not least because agriculture impacts in many different ways and it is not clear how different aspects of sustainability may be in synergy or trade off against each other. We conducted a meta-analysis to assess the relationships between multiple measures of sustainability using novel analytical methods, based around defining the efficiency frontier in the relationship between variables, as well as using correlation analysis. We define 20 grouped variables of agriculture's impact (e.g. on soil, greenhouse gas, water, biodiversity) and find evidence of both strong positive and negative correlations between them. Analysis based on the efficiency frontier suggests that trade-offs can be 'softened' by exploiting the natural between-study variation that arises from a combination of farming best practice and context. Nonetheless, the literature provides strong evidence of the relationship between yields and the negative externalities created by farming across a range of measures. PMID- 26848718 TI - Variation in body mass and morphological characters in Macaca mulatta brevicaudus from Hainan, China. AB - The rhesus macaque (Macaca mulatta) is the most widely distributed nonhuman primate species in the world, with six subspecies distributed through China. From 2012 to 2014, we conducted studies on the body mass and morphological variation of the southernmost subspecies M. m. brevicaudus in Nanwan Nature Reserve for Rhesus Macaque, Hainan, China. We compared measurements with other populations of this species. We also investigated the inter-group body mass variation from seven provisioned free-ranging groups in our study site. Our results show that M. m. brevicaudus has the smallest body size, the smallest body mass, and the shortest tail among rhesus macaque subspecies. Its sexual dimorphism score is also among the lowest, which is similar to other southern distributed subspecies in China, but smaller than northern distributed subspecies. We found that the average body mass of female macaques is not correlated with their dominance ranks. There are significant differences in body mass among the seven adjacent study groups at the same site, suggesting the existence of inter-group competition. Average body mass of a group is better described by a quadratic function of group size than a linear one as predicted by the socio-ecological model. Am. J. Primatol. 78:679 698, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26848720 TI - Increased Plasma S100beta Level in Patients with Major Depressive Disorder. PMID- 26848719 TI - Cue-induced craving to paraphernalia and drug images in opioid dependence. AB - BACKGROUND AND OBJECTIVES: Stimuli that are repeatedly paired with substance use, such as drug paraphernalia, can themselves elicit drug craving. The aim of this study was to examine whether particular cue types elicit greater craving responses than others among individuals with opioid dependence. METHODS: Participants seeking inpatient treatment for opioid dependence were recruited for a study of cue-induced craving. This sample (N = 50), included 25 primary heroin users, 20 primary prescription opioid users, and 5 users of heroin and prescription opioids equally. Participants completed a cue reactivity task, in which images of drug-related stimuli were presented on a computer screen, each followed by a question assessing state drug craving. RESULTS: Overall, participants reported higher craving following paraphernalia stimuli relative to drug stimuli. However, this was moderated by opioid type; there was significantly higher craving in response to images of paraphernalia cues in the heroin group, and higher craving in response to drug cues in the prescription opioid group. DISCUSSION AND CONCLUSIONS: These findings highlight potential differences in cue reactivity to opioid paraphernalia and drug cues, which appears to be moderated by drug type. SCIENTIFIC SIGNIFICANCE: Cue-induced craving is an important factor in relapse. This study adds further to the literature on cue-induced craving in opioid dependence, suggesting that craving may vary based on both cue type and opioid type. Future studies designed to discriminate the impact of substance of abuse, route of administration, and cue type will help to further clarify cue induced craving in this population. PMID- 26848721 TI - Reducing the age of transfused red blood cells in hospitals: ordering and allocation policies. AB - BACKGROUND: Although recent randomized controlled trials have not found increased risk of morbidity/mortality with older red blood cells (RBCs), several large trials will be completed soon providing power to detect smaller risks if indeed they exist. Hence, there may still be a need for inventory management policies that could reduce the age of transfused RBCs without compromising availability or resulting in excessive outdates. MATERIALS AND METHODS: We developed a computer simulation model based on data from an acute care hospital in Hamilton, Ontario. We evaluated and compared the performance of certain practical ordering and allocation policies in terms of outdate rate, shortage rate and the distribution of the age of issued RBCs. RESULTS: During the 1-year period for which we analysed the data, 10349 RBC units were transfused with an average issue age of 20.7 days and six units were outdated (outdate rate: 0.06%). Adopting a strict first in, first out (FIFO) allocation policy and an order-up-to ordering policy with target levels set to five times the estimated daily demand for each blood type, reduced the average issue age by 29.4% (to 14.6 days), without an increase in the outdate rate (0.05%) or resulting in any unmet demand. Further reduction of issue age without a significant increase in outdate rate was observed when adopting non-FIFO threshold-based allocation policies and appropriately adjusting the order-up-to levels. CONCLUSION: A significant reduction of issue age could be possible, without compromising availability or resulting in excessive outdates, by properly adjusting the ordering and allocation policies at the hospital level. PMID- 26848727 TI - Assessment of fetal maturation age by heart rate variability measures using random forest methodology. AB - Fetal maturation age assessment based on heart rate variability (HRV) is a predestinated tool in prenatal diagnosis. To date, almost linear maturation characteristic curves are used in univariate and multivariate models. Models using complex multivariate maturation characteristic curves are pending. To address this problem, we use Random Forest (RF) to assess fetal maturation age and compare RF with linear, multivariate age regression. We include previously developed HRV indices such as traditional time and frequency domain indices and complexity indices of multiple scales. We found that fetal maturation was best assessed by complexity indices of short scales and skewness in state-dependent datasets (quiet sleep, active sleep) as well as in state-independent recordings. Additionally, increasing fluctuation amplitude contributed to the model in the active sleep state. None of the traditional linear HRV parameters contributed to the RF models. Compared to linear, multivariate regression, the mean prediction of gestational age (GA) is more accurate with RF than in linear, multivariate regression (quiet state: R(2)=0,617 vs. R(2)=0,461, active state: R(2)=0,521 vs. R(2)=0,436, state independent: R(2)=0,583 vs. R(2)=0,548). We conclude that classification and regression tree models such as RF methodology are appropriate for the evaluation of fetal maturation age. The decisive role of adjustments between different time scales of complexity may essentially extend previous analysis concepts mainly based on rhythms and univariate complexity indices. Those system characteristics may have implication for better understanding and accessibility of the maturating complex autonomic control and its disturbance. PMID- 26848728 TI - A practical efficient human computer interface based on saccadic eye movements for people with disabilities. AB - Human computer interfaces (HCI) provide new channels of communication for people with severe motor disabilities to state their needs, and control their environment. Some HCI systems are based on eye movements detected from the electrooculogram. In this study, a wearable HCI, which implements a novel adaptive algorithm for detection of saccadic eye movements in eight directions, was developed, considering the limitations that people with disabilities have. The adaptive algorithm eliminated the need for calibration of the system for different users and in different environments. A two-stage typing environment and a simple game for training people with disabilities to work with the system were also developed. Performance of the system was evaluated in experiments with the typing environment performed by six participants without disabilities. The average accuracy of the system in detecting eye movements and blinking was 82.9% at first tries with an average typing rate of 4.5cpm. However an experienced user could achieve 96% accuracy and 7.2cpm typing rate. Moreover, the functionality of the system for people with movement disabilities was evaluated by performing experiments with the game environment. Six people with tetraplegia and significant levels of speech impairment played with the computer game several times. The average success rate in performing the necessary eye movements was 61.5%, which increased significantly with practice up to 83% for one participant. The developed system is 2.6*4.5cm in size and weighs only 15g, assuring high level of comfort for the users. PMID- 26848729 TI - Blood vessel extraction and optic disc removal using curvelet transform and kernel fuzzy c-means. AB - This paper proposes an automatic blood vessel extraction method on retinal images using matched filtering in an integrated system design platform that involves curvelet transform and kernel based fuzzy c-means. Since curvelet transform represents the lines, the edges and the curvatures very well and in compact form (by less number of coefficients) compared to other multi-resolution techniques, this paper uses curvelet transform for enhancement of the retinal vasculature. Matched filtering is then used to intensify the blood vessels' response which is further employed by kernel based fuzzy c-means algorithm that extracts the vessel silhouette from the background through non-linear mapping. For pathological images, in addition to matched filtering, Laplacian of Gaussian filter is also employed to distinguish the step and the ramp like signal from that of vessel structure. To test the efficacy of the proposed method, the algorithm has also been applied to images in presence of additive white Gaussian noise where the curvelet transform has been used for image denoising. Performance is evaluated on publicly available DRIVE, STARE and DIARETDB1 databases and is compared with the large number of existing blood vessel extraction methodologies. Simulation results demonstrate that the proposed method is very much efficient in detecting the long and the thick as well as the short and the thin vessels with an average accuracy of 96.16% for the DRIVE and 97.35% for the STARE database wherein the existing methods fail to extract the tiny and the thin vessels. PMID- 26848731 TI - Disparate bilingual experiences modulate task-switching advantages: A diffusion model analysis of the effects of interactional context on switch costs. AB - Drawing on the adaptive control hypothesis (Green & Abutalebi, 2013), we investigated whether bilinguals' disparate interactional contexts modulate task switching performance. Fifty-eight bilinguals within the single-language context (SLC) and 75 bilinguals within the dual-language context (DLC) were compared in a typical task-switching paradigm. Given that DLC bilinguals switch between languages within the same context, while SLC bilinguals speak only one language in one environment and therefore rarely switch languages, we hypothesized that the two groups' stark difference in their interactional contexts of conversational exchanges would lead to differences in switch costs. As predicted, DLC bilinguals showed smaller switch costs than SLC bilinguals. Our diffusion model analyses suggest that DLC bilinguals' benefits in switch costs are more likely driven by task-set reconfiguration than by proactive interference. Our findings underscore the modulating role of the interactional context of conversational exchanges in task switching. PMID- 26848730 TI - Processing compound words: Evidence from synaesthesia. AB - This study used grapheme-colour synaesthesia, a neurological condition where letters evoke a strong and consistent impression of colour, as a tool to investigate normal language processing. For two sets of compound words varying by lexical frequency (e.g., football vs lifevest) or semantic transparency (e.g., flagpole vs magpie), we asked 19 grapheme-colour synaesthetes to choose their dominant synaesthetic colour using an online colour palette. Synaesthetes could then select a second synaesthetic colour for each word if they experienced one. For each word, we measured the number of elicited synaesthetic colours (zero, one, or two) and the nature of those colours (in terms of their saturation and luminance values). In the first analysis, we found that the number of colours was significantly influenced by compound frequency, such that the probability of a one-colour response increased with frequency. However, semantic transparency did not influence the number of synaesthetic colours. In the second analysis, we found that the luminance of the dominant colour was predicted by the frequency of the first constituent (e.g. rain in rainbow). We also found that the dominant colour was significantly more luminant than the secondary colour. Our results show the influence of implicit linguistic measures on synaesthetic colours, and support multiple/dual-route models of compound processing. PMID- 26848732 TI - Blame, not ability, impacts moral "ought" judgments for impossible actions: Toward an empirical refutation of "ought" implies "can". AB - Recently, psychologists have explored moral concepts including obligation, blame, and ability. While little empirical work has studied the relationships among these concepts, philosophers have widely assumed such a relationship in the principle that "ought" implies "can," which states that if someone ought to do something, then they must be able to do it. The cognitive underpinnings of these concepts are tested in the three experiments reported here. In Experiment 1, most participants judge that an agent ought to keep a promise that he is unable to keep, but only when he is to blame for the inability. Experiment 2 shows that such "ought" judgments correlate with judgments of blame, rather than with judgments of the agent's ability. Experiment 3 replicates these findings for moral "ought" judgments and finds that they do not hold for nonmoral "ought" judgments, such as what someone ought to do to fulfill their desires. These results together show that folk moral judgments do not conform to a widely assumed philosophical principle that "ought" implies "can." Instead, judgments of blame play a modulatory role in some judgments of obligation. PMID- 26848734 TI - Lying despite telling the truth. AB - According to the standard definition of lying an utterance counts as a lie if the agent believes the statement to be false. Thus, according to this view it is possible that a lie states something that happens to be true. This subjective view on lying has recently been challenged by Turri and Turri (2015) who presented empirical evidence suggesting that people only consider statements as lies that are objectively false (objective view). We argue that the presented evidence is in fact consistent with the standard subjective view if conversational pragmatics is taken into account. Three experiments are presented that directly test and support the subjective view. An additional experiment backs up our pragmatic hypothesis by using the uncontroversial case of making a promise. PMID- 26848733 TI - The relevance effect and conditionals. AB - More than a decade of research has found strong evidence for P(if A, then C)=P(C|A) ("the Equation"). We argue, however, that this hypothesis provides an overly simplified picture due to its inability to account for relevance. We manipulated relevance in the evaluation of the probability and acceptability of indicative conditionals and found that relevance moderates the effect of P(C|A). This corroborates the Default and Penalty Hypothesis put forward in this paper. Finally, the probability and acceptability of concessive conditionals ("Even if A, then still C") were investigated and it was found that the Equation provides a better account of concessive conditionals than of indicatives across relevance manipulations. PMID- 26848735 TI - I've got your number: Spontaneous perspective-taking in an interactive task. AB - Thinking about how other people represent objects in the world around them is thought to require deliberate effort. In recent years, interactive "joint action" paradigms have shown how social context can affect our cognitive processing. We tested whether people would represent their partner's point of view in a simple team game. Participants played a game in which they had to judge the magnitude of a number either sat alone, or opposite a partner. Importantly they were never asked to judge their partner's point of view. Remarkably, when playing the game as a team, people were better when their partner happened to share their view of the number, such as when seeing a number 8, than when their partner viewed the number to be different, such as when seeing a number 6 that looked like a number 9 to their partner. In two further experiments, we identified the conditions under which the effect was present. Experiment two showed that the effect was only present after observing the prior involvement of one's partner in the task. Experiment 3, showed that the aspect of the stimulus (its magnitude) that participants were sensitive to did not need to be the aspect of the stimulus to which their partner was paying attention. PMID- 26848737 TI - UPLC-MS/MS assay of 21-aminosteroid (lazaroid U74389G) for application in pharmacokinetic study. AB - Lazaroids are potent inhibitors of lipid peroxidation, both in vitro and in vivo. Additionally, a member of the lazaroid family, U-74389G (LAZ) has been shown to have specific radio-protective and anti-proliferative effects. However, there is no quantitative analytical method developed for measuring the therapeutic levels of LAZ for the aforementioned effects. This article highlights the development and validation of a sensitive UPLC-MS/MS method for the quantification of LAZ, and its subsequent application in pharmacokinetic studies in rats with the lower limit of quantification (LLOQ) of 1.95 ng/mL. LAZ and internal standard diadzein (IS) were separated using ACQUITY UPLC((r)) BEH C18 column. Gradient elution was used at a flow rate of 0.45 mL/min with mobile phases consisting of 0.1% formic acid in water and 0.1% formic in acetonitrile. LAZ (m/z 612->260) and IS (m/z 255 >199) were detected by electrospray ionization (ESI) using multiple reaction monitoring (MRM) in a positive mode on QTRAP((r)) 5500 System. The UPLC-MS/MS method was validated as per the US FDA Guidelines for Bio-analytical Validation. LAZ was extracted from rat plasma (100 MUL) using protein precipitation by acetonitrile with mean recovery and matrix factor in range of 47.7-56.1%, and 85.6-89.4%, respectively. The calibration curve for LAZ was linear in the range of 1.95-250 ng/mL. The inter-day and intra-day accuracy and precision values for LLOQ, low, medium, high and very high concentration QC samples were within +/ 15%. LAZ was tested under different storage conditions, for short-term bench-top stability (1h and 3h at 25 degrees C), long-term stability (1 month at -80 degrees C), freeze-thaw cycle stability (1 cycle and 3 cycles) and stability of processed samples in auto-sampler (24h at 10 degrees C) with stability values within +/-15% range of nominal concentrations. The validated UPLC-MS/MS method was further applied to a pharmacokinetic study in rats after a single intravenous dose of LAZ at 5 mg/kg. PMID- 26848736 TI - Smoke and mirrors: Testing the scope of chimpanzees' appearance-reality understanding. AB - The ability to make appearance-reality (AR) discriminations is an important higher-order cognitive adaptation in humans but is still poorly understood in our closest primate relatives. Previous research showed that chimpanzees are capable of AR discrimination when choosing between food items that appear, due to the effects of distorting lenses, to be smaller or larger than they actually are (Krachun, Call, & Tomasello, 2009). In the current study, we investigated the scope and flexibility of chimpanzees' AR discrimination abilities by presenting them with a wider range of illusory stimuli. In addition to using lenses to change the apparent size of food items (Experiment 1), we used a mirror to change the apparent number of items (Experiment 2), and tinted filters to change their apparent color (Experiment 3). In all three experiments, some chimpanzees were able to maximize their food rewards by making a choice based on the real properties of the stimuli in contrast to their manifest apparent properties. These results replicate the earlier findings for size illusions and extend them to additional situations involving illusory number and color. Control tests, together with findings from previous studies, ruled out lower-level explanations for the chimpanzees' performance. The findings thus support the hypothesis that chimpanzees are capable of making AR discriminations with a range of illusory stimuli. PMID- 26848738 TI - Characterisation of "Catalao" and "Salsichao" Portuguese traditional sausages with salt reduction. AB - The present study evaluated the effect of salt reduction on traditional dry-cured sausages' safety, quality and product acceptance, comprising physicochemical and microbiological parameters, biogenic amines, fatty acids, texture profile and sensory analysis. According to our results, salt content had a major effect on microbiological counts, although not compromising the products' safety. Marked differences were identified regarding biogenic amines, in particular for histamine, tyramine and cadaverine, which were detected in larger amounts in products with 3%. Moreover, significant differences in the fatty acids profile have also been found, but only in less abundant components such as linoleic, lauric and heneicosanoic acids. Texture profile analysis of low-salt products, revealed a decrease in hardness and chewiness, along with an increase in adhesiveness values. Sensory evaluations revealed that despite the less intense aroma, products with 3% salt, had a more balanced salt perception. Our results suggest that salt content may be reduced to 50% in dry-cured products, with the obvious health-related advantages. PMID- 26848740 TI - Modeling the Structure of Complex Aluminosilicate Glasses: The Effect of Zinc Addition. AB - An empirical potential structure refinement of neutron and X-ray diffraction data combined with extended absorption fine structure evidence has been applied to the investigation of two distinct sets of complex aluminosilicate glasses containing different quantities of zinc. Data come from (i) neutron and X-ray total scattering experiments, which have been performed at the ISIS neutron spallation source (SANDALS beamline) and at the European Synchrotron Radiation Facility (ID11 beamline), and (ii) EXAFS experiments which have been performed at the European Synchrotron Radiation Facility (BM23 beamline). By careful examination of the modeled ensemble of atoms, a wide range of structural information has been extracted: coordination numbers, bond distances, cluster sizes, type of oxygen sharing, and the preference of large cations to adopt a charge-compensating role. The first series of glasses, which is characterized by a fixed network modifier element content (i.e., Na), shows how the introduction of Zn at the expense of Si and Al network forming elements does not significantly alter the polymerization degree, as a result of its dominant 4-fold coordination. In the case of the second series, which is characterized by fixed network forming element content (i.e., Si and Al), it is shown how the replacement of a network modifier element (i.e., Ca) with the introduction of Zn does not change the propensity of Zn to be mainly 4-fold coordinated by promoting the network. Where appropriate the experimental results have been compared with classical theoretical approaches such as stoichiometric models based on Zachariasen's rules and computational routines. PMID- 26848739 TI - Versatile Protecting-Group Free Tetrazolomethane Amine Synthesis by Ugi Reaction. AB - The use of ammonia in the Ugi reaction is often problematic due to low yields and multiple side reactions. Here, we report the use of ammonia in the tetrazole Ugi variation providing a clean, good-to-high yielding reaction, especially with ketones as oxo components. The scope and limitations of this reaction and a structure-reactivity relationship are provided by performing >85 reactions. The primary amine component of the alpha-amino tetrazole is a versatile starting material for further reactions. PMID- 26848741 TI - Thermal Stabilization of Metal-Organic Framework-Derived Single-Site Catalytic Clusters through Nanocasting. AB - Metal-organic frameworks (MOFs) provide convenient systems for organizing high concentrations of single catalytic sites derived from metallic or oxo-metallic nodes. However, high-temperature processes cause agglomeration of these nodes, so that the single-site character and catalytic activity are lost. In this work, we present a simple nanocasting approach to provide a thermally stable secondary scaffold for MOF-based catalytic single sites, preventing their aggregation even after exposure to air at 600 degrees C. We describe the nanocasting of NU-1000, a MOF with 3 nm channels and Lewis-acidic oxozirconium clusters, with silica. By condensing tetramethylorthosilicate within the NU-1000 pores via a vapor-phase HCl treatment, a silica layer is created on the inner walls of NU-1000. This silica layer provides anchoring sites for the oxozirconium clusters in NU-1000 after the organic linkers are removed at high temperatures. Differential pair distribution functions obtained from synchrotron X-ray scattering confirmed that isolated oxozirconium clusters are maintained in the heated nanocast materials. Pyridine adsorption experiments and a glucose isomerization reaction demonstrate that the clusters remain accessible to reagents and maintain their acidic character and catalytic activity even after the nanocast materials have been heated to 500-600 degrees C in air. Density functional theory calculations show a correlation between the Lewis acidity of the oxozirconium clusters and their catalytic activity. The ability to produce MOF-derived materials that retain their catalytic properties after exposure to high temperatures makes nanocasting a useful technique for obtaining single-site catalysts suitable for high temperature reactions. PMID- 26848742 TI - Contribution of Visual Information about Ball Trajectory to Baseball Hitting Accuracy. AB - The contribution of visual information about a pitched ball to the accuracy of baseball-bat contact may vary depending on the part of trajectory seen. The purpose of the present study was to examine the relationship between hitting accuracy and the segment of the trajectory of the flying ball that can be seen by the batter. Ten college baseball field players participated in the study. The systematic error and standardized variability of ball-bat contact on the bat coordinate system and pitcher-to-catcher direction when hitting a ball launched from a pitching machine were measured with or without visual occlusion and analyzed using analysis of variance. The visual occlusion timing included occlusion from 150 milliseconds (ms) after the ball release (R+150), occlusion from 150 ms before the expected arrival of the launched ball at the home plate (A 150), and a condition with no occlusion (NO). Twelve trials in each condition were performed using two ball speeds (31.9 m.s-1 and 40.3 m.s-1). Visual occlusion did not affect the mean location of ball-bat contact in the bat's long axis, short axis, and pitcher-to-catcher directions. Although the magnitude of standardized variability was significantly smaller in the bat's short axis direction than in the bat's long axis and pitcher-to-catcher directions (p < 0.001), additional visible time from the R+150 condition to the A-150 and NO conditions resulted in a further decrease in standardized variability only in the bat's short axis direction (p < 0.05). The results suggested that there is directional specificity in the magnitude of standardized variability with different visible time. The present study also confirmed the limitation to visual information is the later part of the ball trajectory for improving hitting accuracy, which is likely due to visuo-motor delay. PMID- 26848743 TI - Irradiation Decreases the Neuroendocrine Biomarker Pro-Opiomelanocortin in Small Cell Lung Cancer Cells In Vitro and In Vivo. AB - BACKGROUND: Small cell lung cancer (SCLC) is an extremely aggressive disease, commonly displaying therapy-resistant relapse. We have previously identified neuroendocrine and epithelial phenotypes in SCLC tumours and the neuroendocrine marker, pro-opiomelanocortin (POMC), correlated with worse overall survival in patients. However, the effect of treatment on these phenotypes is not understood. The current study aimed to determine the effect of repeated irradiation treatment on SCLC cell phenotype, focussing on the neuroendocrine marker, POMC. RESULTS: Human SCLC cells (DMS 79) were established as subcutaneous xenograft tumours in CBA nude mice and then exposed to repeated 2Gy irradiation. In untreated animals, POMC in the blood closely mirrored tumour growth; an ideal characteristic for a circulating biomarker. Following repeated localised irradiation in vivo, circulating POMC decreased (p< 0.01), in parallel with a decrease in tumour size, but remained low even when the tumours re-established. The excised tumours displayed reduced and distinctly heterogeneous expression of POMC compared to untreated tumours. There was no difference in the epithelial marker, cytokeratin. However, there were significantly more N-cadherin positive cells in the irradiated tumours. To investigate the tumour response to irradiation, DMS79 cells were repeatedly irradiated in vitro and the surviving cells selected. POMC expression was reduced, while mesenchymal markers N-cadherin, beta1-integrin, fibroblast-specific protein 1, beta-catenin and Zeb1 expression were amplified in the more irradiation-primed cells. There were no consistent changes in epithelial marker expression. Cell morphology changed dramatically with repeatedly irradiated cells displaying a more elongated shape, suggesting a switch to a more mesenchymal phenotype. CONCLUSIONS: In summary, POMC biomarker expression and secretion were reduced in SCLC tumours which regrew after irradiation and in repeatedly irradiation (irradiation-primed) cells. Therefore, POMC was no longer predictive of tumour burden. This highlights the importance of fully evaluating biomarkers during and after therapy to assess clinical utility. Furthermore, the gain in mesenchymal characteristics in irradiated cells could be indicative of a more invasive phenotype. PMID- 26848744 TI - Reassessment of Species Diversity of the Subfamily Denticollinae (Coleoptera: Elateridae) through DNA Barcoding. AB - The subfamily Denticollinae is a taxonomically diverse group in the family Elateridae. Denticollinae includes many morphologically similar species and crop pests, as well as many undescribed species at each local fauna. To construct a rapid and reliable identification system for this subfamily, the effectiveness of molecular species identification was assessed based on 421 cytochrome c oxidase subunit I (COI) sequences of 84 morphologically identified species. Among the 84 morphospecies, molecular species identification of 60 species (71.4%) was consistent with their morphological identifications. Six cryptic and/or pseudocryptic species with large genetic divergence (>5%) were confirmed by their sympatric or allopatric distributions. However, 18 species, including a subspecies, had ambiguous genetic distances and shared overlapping intra- and interspecific genetic distances (range: 2.12%-3.67%) suggesting incomplete lineage sorting, introgression of mitochondrial genome, or affection by endosymbionts, such as Wolbachia infection, between species and simple genetic variation within species. In this study, we propose a conservative threshold of 3.6% for convenient molecular operational taxonomic unit (MOTU) identification in the subfamily Denticollinae based on the results of pairwise genetic distances analyses using neighbor-joining, mothur, Automatic Barcode Gap Discovery analysis, and tree-based species delimitation by Poisson Tree Processes analysis. Using the 3.6% threshold, we identified 87 MOTUs and found 8 MOTUs in the interval between 2.5% to 3.5%. Evaluation of MOTUs identified in this range requires integrative species delimitation, including review of morphological and ecological differences as well as sensitive genetic markers. From this study, we confirmed that COI sequence is useful for reassessing species diversity for polymorphic and polytypic species occurring in sympatric and allopatric distributions, and for a single species having an extensively large habitat. PMID- 26848745 TI - The Mind-Writing Pupil: A Human-Computer Interface Based on Decoding of Covert Attention through Pupillometry. AB - We present a new human-computer interface that is based on decoding of attention through pupillometry. Our method builds on the recent finding that covert visual attention affects the pupillary light response: Your pupil constricts when you covertly (without looking at it) attend to a bright, compared to a dark, stimulus. In our method, participants covertly attend to one of several letters with oscillating brightness. Pupil size reflects the brightness of the selected letter, which allows us-with high accuracy and in real time-to determine which letter the participant intends to select. The performance of our method is comparable to the best covert-attention brain-computer interfaces to date, and has several advantages: no movement other than pupil-size change is required; no physical contact is required (i.e. no electrodes); it is easy to use; and it is reliable. Potential applications include: communication with totally locked-in patients, training of sustained attention, and ultra-secure password input. PMID- 26848746 TI - Creating an Animal Model of Tendinopathy by Inducing Chondrogenic Differentiation with Kartogenin. AB - Previous animal studies have shown that long term rat treadmill running induces over-use tendinopathy, which manifests as proteoglycan accumulation and chondrocytes-like cells within the affected tendons. Creating this animal model of tendinopathy by long term treadmill running is however time-consuming, costly and may vary among animals. In this study, we used a new approach to develop an animal model of tendinopathy using kartogenin (KGN), a bio-compound that can stimulate endogenous stem/progenitor cells to differentiate into chondrocytes. KGN-beads were fabricated and implanted into rat Achilles tendons. Five weeks after implantation, chondrocytes and proteoglycan accumulation were found at the KGN implanted site. Vascularity as well as disorganization in collagen fibers were also present in the same site along with increased expression of the chondrocyte specific marker, collagen type II (Col. II). In vitro studies confirmed that KGN was released continuously from KGN-alginate in vivo beads and induced chondrogenic differentiation of tendon stem/progenitor cells (TSCs) suggesting that chondrogenesis after KGN-bead implantation into the rat tendons is likely due to the aberrant differentiation of TSCs into chondrocytes. Taken together, our results showed that KGN-alginate beads can be used to create a rat model of tendinopathy, which, at least in part, reproduces the features of over use tendinopathy model created by long term treadmill running. This model is mechanistic (stem cell differentiation), highly reproducible and precise in creating localized tendinopathic lesions. It is expected that this model will be useful to evaluate the effects of various topical treatments such as NSAIDs and platelet-rich plasma (PRP) for the treatment of tendinopathy. PMID- 26848748 TI - Correction: Correction: Improved Detection of Common Variants Associated with Schizophrenia and Bipolar Disorder Using Pleiotropy-Informed Conditional False Discovery Rate. PMID- 26848747 TI - Association between Seminal Vesicle Invasion and Prostate Cancer Detection Location after Transrectal Systemic Biopsy among Men Who Underwent Radical Prostatectomy. AB - BACKGROUND: Our hypothesis is that the location of the seminal vesicles near the base of the prostate, the more positive cores are detected in the base, the greater the risk of seminal vesicle invasion. Therefore we investigate the clinical outcomes of base dominant prostate cancer (BDPC) in transrectal ultrasound (TRUS) -guided biopsies compared with anteromiddle dominant prostate cancer (AMPC). METHODS: From November 2003 to June 2014, a total of 990 intermediate and high risk prostate cancer (PCa) patients who underwent radical prostatectomy (RP) were enrolled and stratified into two groups according to proportion of positive cores-BDPC group had >= 33.3% ratio of positive cores from the prostate base among all positive cores and AMPC group < 33.3% in systemic biopsy. Between two groups, we compared the rate of pathologic outcomes and biochemical recurrence (BCR). We performed multivariate logistic regression model to confirm the significance of BDPC to seminal vesicle invasion (SVI) and Cox proportional hazard analysis to BCR. RESULTS: Among these 990 PCa patients, the 487 patients in BDPC group had more advanced clinical stage (p<0.001), a higher biopsy GS (p = 0.002), and a higher rate of extracapsular extension (ECE), SVI and BCR (all p<0.001) than AMPC group. The patients in BDPC group had poor BCR free survival rate via Kaplan-meier analysis (p<0.001). The ratio of the base positive cores was a significant predictor to SVI in multivariate analysis (p < 0.001) and significant predictor of BCR in multivariate Cox proportional analysis (hazard ratio: 1.466, p = 0.004). CONCLUSIONS: BDPC in TRUS-guided prostate biopsies was significantly associated with SVI and BCR after adjusting for other clinical factors. Therefore, BDPC should be considered to be a more aggressive tumor despite an otherwise similar cancer profile. PMID- 26848749 TI - Comparison of Metabolites Variation and Antiobesity Effects of Fermented versus Nonfermented Mixtures of Cudrania tricuspidata, Lonicera caerulea, and Soybean According to Fermentation In Vitro and In Vivo. AB - We used ultra-performance-liquid-chromatography with quadrupole-time-of-flight mass spectrometry to study the changes in metabolites in the mixture of Cudrania tricuspidata, Lonicera caerulea, and soybean (CLM) during fermentation. Additionally, the antiobesity effects of CLM and fermented-CLM (FCLM) were studied based on the analysis of plasma from high-fat diet (HFD)-fed mice. The levels of cyanidin and the glycosides of luteolin, quercetin, and cyanidin derived from L. caerulea were decreased, whereas the levels of luteolin and quercetin were increased during fermentation. Isoflavone glycosides and soyasaponins originating from the soybean were decreased, whereas their aglycones such as daidzein, glycitein, and genistein were increased. As for prenylated flavonoids from C. tricuspidata, these metabolites were decreased at the early stage of fermentation, and were increased at end of the fermentation. In terms of the functional food product, various metabolites derived from diverse natural products in CLM had complementary effects and demonstrated higher antioxidant and pancreatic lipase inhibition activities after fermentation; these activities were closely related to flavonoid aglycones including genistein, daidzein, glycitein, luteolin, and quercetin. In an in vivo experiment, several clinical parameters affected by HFD were improved by the administration of either CLM or FCLM, but there was a difference in the antiobesity effects. The levels of lysoPCs with C20:4, C16:0, and C22:6 were significantly attenuated by CLM administration, while the attenuated levels of lysoPCs with C20:4 and C18:2 were significantly restored by FCLM administration. These metabolites may explain the above mentioned differences in antiobesity effects. Although only the changes in plasma lysophospholipids could not fully explain antiobesity effects between non fermented and fermented plant mixtures from our results, we suggest that metabolomics approach could provide a way to reveal the metabolite alterations in the complex fermentation process and understand the differences or changes in bioactivity according to fermentation. PMID- 26848750 TI - Knowledge, Attitudes and Perceptions of Saudis towards Participating in Clinical Trials. AB - AIM: To assess the knowledge, attitudes, and perceptions of Saudis towards participating in clinical trials (CTs). METHODS: A cross-sectional study was conducted on 232 Saudi adult patients and their companions visiting adult outpatient clinics at King Fahad Medical City, Riyadh, Saudi Arabia. Data were collected using a self-administered questionnaire based on information obtained from the literature. The questionnaire was divided into four sections, one covering the respondents' demographics, and the other three assessing knowledge, attitudes, and perceptions towards participating in CTs. RESULTS: A total of 148 (63.8%) respondents were males, and 52 (22.4%) participants had been invited to participate in a CT previously. Of those, 39 (75%) participated. Knowledge about the essential elements of informed consent ranged from 55.7% (number of participants needed) to 85.7% (confidentiality of personal information). The majority (163, 73.8%) of respondents was willing to participate in a CT after consulting their family physician and 130 (58.0%) respondents would be motivated to participate in a CT if they were healthy. Only 36.8% of the respondents believed that patients who participated in a CT received the best care. Moreover, 110 (48.7%) respondents believed that research was conducted in a responsible and ethical manner. CONCLUSIONS: The present study assessed the current understanding of CTs among Saudi participants. Although the majority of participants had an acceptable level of knowledge about CTs, they exhibited conditional attitudes and misperceptions towards participating in a CT. Increased patient awareness may improve patients' attitudes towards ethical conduct of CTs. PMID- 26848751 TI - The Effect of (-)-Epigallocatechin-3-Gallate on IL-1beta Induced IL-8 Expression in Orbital Fibroblast from Patients with Thyroid-Associated Ophthalmopathy. AB - Orbital fibroblasts have been reported to be an important effector cells for the development of thyroid-associated ophthalmopathy (TAO). Orbital fibroblasts secrete various inflammatory cytokines in response to an inflammatory stimulation, leading to TAO-related tissue swelling. It has also been reported that (-)-epigallocatechin-3-gallate (EGCG), a major polyphenolic constituent of green tea, has antioxidant and anti-inflammatory properties. In the current study, we investigated the issue of whether or how EGCG affects the interleukin (IL)-1beta-induced secretion of IL-8 in human orbital fibroblasts from TAO patients. Treatment with EGCG significantly reduced the level of IL-1beta-induced secretion of IL-8 and the expression of IL-8 mRNA. IL-1beta-induced the degradation of IkappaBalpha, and the phosphorylation of p38 and ERK, and the IL 1beta-induced expression of IL-8 mRNA was inhibited by specific inhibitors, such as BAY-117085 for NF-kB, SB203580 for p38, and PD98059 for ERK. In addition, treatment with EGCG inhibited the IL-1beta-induced degradation of IkappaBalpha, and the phosphorylation of p38 and ERK. However, pre-treatment with antioxidants, NVN and NAC, which suppressed ROS generation, did not reduce IL-8 expression in IL-1beta-treated orbital fibroblasts, suggesting that the IL-1beta-induced IL-8 expression is not mediated by the generation of ROS. These results show that EGCG suppresses the IL-1beta-induced expression of IL-8 through inhibition of the NF kappaB, p38, and ERK pathways. These findings could contribute to the development of new types of EGCG-containing pharmacological agents for use in the treatment of TAO. PMID- 26848752 TI - Genome of Cnaphalocrocis medinalis Granulovirus, the First Crambidae-Infecting Betabaculovirus Isolated from Rice Leaffolder to Sequenced. AB - Cnaphalocrocis medinalis is a major pest of rice in South and South-East Asia. Insecticides are the major means farmers use for management. A naturally occurring baculovirus, C. medinalis granulovirus (CnmeGV), has been isolated from the larvae and this has the potential for use as microbial agent. Here, we described the complete genome sequence of CnmeGV and compared it to other baculovirus genomes. The genome of CnmeGV is 112,060 base pairs in length, has a G+C content of 35.2%. It contains 133 putative open reading frames (ORFs) of at least 150 nucleotides. A hundred and one (101) of these ORFs are homologous to other baculovirus genes including 37 baculovirus core genes. Thirty-two (32) ORFs are unique to CnmeGV with no homologues detected in the GeneBank and 53 tandem repeats (TRs) with sequence length from 25 to 551 nt intersperse throughout the genome of CnmeGV. Six (6) homologous regions (hrs) were identified interspersed throughout the genome. Hr2 contains 11 imperfect palindromes and a high content of AT sequence (about 73%). The unique ORF28 contains a coiled-coil region and a zinc finger-like domain of 4-50 residues specialized by two C2C2 zinc finger motifs that putatively bound two atoms of zinc. ORF21 encoding a chit-1 protein suggesting a horizontal gene transfer from alphabaculovirus. The putative protein presents two carbohydrate-binding module family 14 (CBM_14) domains rather than other homologues detected from betabaculovirus that only contains one chit binding region. Gene synteny maps showed the colinearity of sequenced betabaculovirus. Phylogenetic analysis indicated that CnmeGV grouped in the betabaculovirus, with a close relation to AdorGV. The cladogram obtained in this work grouped the 17 complete GV genomes in one monophyletic clade. CnmeGV represents a new crambidae host-isolated virus species from the genus Betabaculovirus and is most closely relative of AdorGV. The analyses and information derived from this study will provide a better understanding of the pathological symptoms caused by this virus and its potential use as a microbial pesticide. PMID- 26848753 TI - Pancake kidney with a single ureter: a rare incidental observation at autopsy. AB - We report an extremely rare case of a pancake kidney with a single ureter. During the medicolegal autopsy on the body of a traffic accident victim, the kidneys were not located in the abdomen. The anterior surfaces of both kidneys were completely fused in the pelvic cavity, and the kidney was shaped like a pancake. This pancake kidney had accessory renal arteries around it and one renal vein from each kidney. The left renal vein was much smaller in diameter than the right one. There were two major calyces, one each from each kidney. The major calyces joined to form a single renal pelvis from both the kidneys, which continued as a single ureter. The renal pelvis and ureter lay posterior to the pancake kidney. Urologists and pelvic surgeons should be aware of the variant anatomy of the pancake kidney, particularly concerning its vasculature, to prevent unexpected catastrophic bleeding. If the kidneys are not located in the abdominal cavity, the autopsy surgeon must consider the possibility of its presence in the pelvic cavity. This could be especially important during medicolegal investigations into allegations of missing kidneys and unlawful kidney transplantations. PMID- 26848754 TI - Transcriptome Profiling of Beach Morning Glory (Ipomoea imperati) under Salinity and Its Comparative Analysis with Sweetpotato. AB - The response and adaption to salt remains poorly understood for beach morning glory [Ipomoea imperati (Vahl) Griseb], one of a few relatives of sweetpotato, known to thrive under salty and extreme drought conditions. In order to understand the genetic mechanisms underlying salt tolerance of a Convolvulaceae member, a genome-wide transcriptome study was carried out in beach morning glory by 454 pyrosequencing. A total of 286,584 filtered reads from both salt stressed and unstressed (control) root and shoot tissues were assembled into 95,790 unigenes with an average length of 667 base pairs (bp) and N50 of 706 bp. Putative differentially expressed genes (DEGs) were identified as transcripts overrepresented under salt stressed tissues compared to the control, and were placed into metabolic pathways. Most of these DEGs were involved in stress response, membrane transport, signal transduction, transcription activity and other cellular and molecular processes. We further analyzed the gene expression of 14 candidate genes of interest for salt tolerance through quantitative reverse transcription PCR (qRT-PCR) and confirmed their differential expression under salt stress in both beach morning glory and sweetpotato. The results comparing transcripts of I. imperati against the transcriptome of other Ipomoea species, including sweetpotato are also presented in this study. In addition, 6,233 SSR markers were identified, and an in silico analysis predicted that 434 primer pairs out of 4,897 target an identifiable homologous sequence in other Ipomoea transcriptomes, including sweetpotato. The data generated in this study will help in understanding the basics of salt tolerance of beach morning glory and the SSR resources generated will be useful for comparative genomics studies and further enhance the path to the marker-assisted breeding of sweetpotato for salt tolerance. PMID- 26848756 TI - Sharing of Needles and Syringes among Men Who Inject Drugs: HIV Risk in Northwest Bangladesh. AB - INTRODUCTION: Injection drug use is prevalent in northwestern Bangladesh. We sought to explore the context of needle/syringe sharing among persons who inject drugs (PWID), examining risk exposures to blood-borne infections like the human immunodeficiency virus (HIV) and hepatitis in a region where these dual epidemics are likely to expand. METHODS: We used a qualitative research approach to learn about injection practices, conducting 60 in-depth interviews among PWID. We then conducted 12 focus group discussions (FGDs) that generated a checklist of salient issues, and followed up with personal observations of typical days at the drug use venues. Content and interpretative frameworks were used to analyze qualitative information and socio-demographic information, using SPSS software. RESULTS: We found that needle/syringe-sharing behaviours were integrated into the overall social and cultural lives of drug users. Sharing behaviours were an central component of PWID social organization. Sharing was perceived as an inherent element within reciprocal relationships, and sharing was tied to beliefs about drug effects, economic adversity, and harassment due to their drug user status. Carrying used needles/syringes to drug-use venues was deemed essential since user-unfriendly needle-syringe distribution schedules of harm reduction programmes made it difficult to access clean needles/syringes in off-hours. PWID had low self-esteem. Unequal power relationships were reported between the field workers of harm reduction programmes and PWID. Field workers expressed anti-PWID bias and judgmental attitudes, and also had had misconceptions about HIV and hepatitis transmission. PWID were especially disturbed that no assistance was forthcoming from risk reduction programme staff when drug users manifested withdrawal symptoms. CONCLUSION: Interventions must take social context into account when scaling up programmes in diverse settings. The social organization of PWID include values that foster needle-syringe sharing. Utilization and impact of risk reduction programmes might be improved with expanded clean needle/syringe distribution at times and venues convenient for PWID, better trained and non judgmental staff, and medical assistance for health problems, including drug withdrawal symptoms. PMID- 26848755 TI - Cross-Modal and Intra-Modal Characteristics of Visual Function and Speech Perception Performance in Postlingually Deafened, Cochlear Implant Users. AB - Evidence of visual-auditory cross-modal plasticity in deaf individuals has been widely reported. Superior visual abilities of deaf individuals have been shown to result in enhanced reactivity to visual events and/or enhanced peripheral spatial attention. The goal of this study was to investigate the association between visual-auditory cross-modal plasticity and speech perception in post-lingually deafened, adult cochlear implant (CI) users. Post-lingually deafened adults with CIs (N = 14) and a group of normal hearing, adult controls (N = 12) participated in this study. The CI participants were divided into a good performer group (good CI, N = 7) and a poor performer group (poor CI, N = 7) based on word recognition scores. Visual evoked potentials (VEP) were recorded from the temporal and occipital cortex to assess reactivity. Visual field (VF) testing was used to assess spatial attention and Goldmann perimetry measures were analyzed to identify differences across groups in the VF. The association of the amplitude of the P1 VEP response over the right temporal or occipital cortex among three groups (control, good CI, poor CI) was analyzed. In addition, the association between VF by different stimuli and word perception score was evaluated. The P1 VEP amplitude recorded from the right temporal cortex was larger in the group of poorly performing CI users than the group of good performers. The P1 amplitude recorded from electrodes near the occipital cortex was smaller for the poor performing group. P1 VEP amplitude in right temporal lobe was negatively correlated with speech perception outcomes for the CI participants (r = -0.736, P = 0.003). However, P1 VEP amplitude measures recorded from near the occipital cortex had a positive correlation with speech perception outcome in the CI participants (r = 0.775, P = 0.001). In VF analysis, CI users showed narrowed central VF (VF to low intensity stimuli). However, their far peripheral VF (VF to high intensity stimuli) was not different from the controls. In addition, the extent of their central VF was positively correlated with speech perception outcome (r = 0.669, P = 0.009). Persistent visual activation in right temporal cortex even after CI causes negative effect on outcome in post-lingual deaf adults. We interpret these results to suggest that insufficient intra-modal (visual) compensation by the occipital cortex may cause negative effects on outcome. Based on our results, it appears that a narrowed central VF could help identify CI users with poor outcomes with their device. PMID- 26848757 TI - Acute Mountain Sickness Symptom Severity at the South Pole: The Influence of Self Selected Prophylaxis with Acetazolamide. AB - INTRODUCTION: Acetazolamide, a carbonic anhydrase inhibitor, remains the only FDA approved pharmaceutical prophylaxis for acute mountain sickness (AMS) though its effectiveness after rapid transport in real world conditions is less clear. METHODS: Over 2 years, 248 healthy adults traveled by airplane from sea level (SL) to the South Pole (ALT, ~3200m) and 226 participants provided Lake Louise Symptom Scores (LLSS) on a daily basis for 1 week; vital signs, blood samples, and urine samples were collected at SL and at ALT. Acetazolamide was available to any participant desiring prophylaxis. Comparisons were made between the acetazolamide with AMS (ACZ/AMS) (n = 42), acetazolamide without AMS (ACZ/No AMS)(n = 49), no acetazolamide with AMS (No ACZ/AMS) (n = 56), and the no acetazolamide without AMS (No ACZ/No AMS) (n = 79) groups. Statistical analysis included Chi-squared and one-way ANOVA with Bonferroni post-hoc tests. Significance was p<=0.05. RESULTS: No significant differences were found for between-group characteristics or incidence of AMS between ACZ and No ACZ groups. ACZ/AMS reported greater LLSS, BMI, and red cell distribution width. ACZ/No AMS had the highest oxygen saturation (O2Sat) at ALT. No significant differences were found in serum electrolyte concentrations or PFT results. DISCUSSION: Acetazolamide during rapid ascent provided no apparent protection from AMS based on LLSS. However, it is unclear if this lack of effect was directly associated with the drug or if perhaps there was some selection bias with individuals taking ACZ more likely to have symptoms or if there may have been more of perceptual phenomenon related to a constellation of side effects. PMID- 26848758 TI - Facial Mechanosensory Influence on Forelimb Movement in Newborn Opossums, Monodelphis domestica. AB - The opossum, Monodelphis domestica, is born very immature but crawls, unaided, with its forelimbs (FL) from the mother's birth canal to a nipple where it attaches to pursue its development. What sensory cues guide the newborn to the nipple and trigger its attachment to it? Previous experiments showed that low intensity electrical stimulation of the trigeminal ganglion induces FL movement in in vitro preparations and that trigeminal innervation of the facial skin is well developed in the newborn. The skin does not contain Vater-Pacini or Meissner touch corpuscles at this age, but it contains cells which appear to be Merkel cells (MC). We sought to determine if touch perceived by MC could exert an influence on FL movements. Application of the fluorescent dye AM1-43, which labels sensory cells such as MC, revealed the presence of a large number of labeled cells in the facial epidermis, especially in the snout skin, in newborn opossums. Moreover, calibrated pressure applied to the snout induced bilateral and simultaneous electromyographic responses of the triceps muscle in in vitro preparations of the neuraxis and FL from newborn. These responses increase with stimulation intensity and tend to decrease over time. Removing the facial skin nearly abolished these responses. Metabotropic glutamate 1 receptors being involved in MC neurotransmission, an antagonist of these receptors was applied to the bath, which decreased the EMG responses in a reversible manner. Likewise, bath application of the purinergic type 2 receptors, used by AM1-43 to penetrate sensory cells, also decreased the triceps EMG responses. The combined results support a strong influence of facial mechanosensation on FL movement in newborn opossums, and suggest that this influence could be exerted via MC. PMID- 26848759 TI - The Arginine Methyltransferase PRMT6 Cooperates with Polycomb Proteins in Regulating HOXA Gene Expression. AB - Protein arginine methyltransferase 6 (PRMT6) catalyses asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a), which has been shown to impede the deposition of histone H3 lysine 4 trimethylation (H3K4me3) by blocking the binding and activity of the MLL1 complex. Importantly, the genomic occurrence of H3R2me2a has been found to coincide with histone H3 lysine 27 trimethylation (H3K27me3), a repressive histone mark generated by the Polycomb repressive complex 2 (PRC2). Therefore, we investigate here a putative crosstalk between PRMT6- and PRC-mediated repression in a cellular model of neuronal differentiation. We show that PRMT6 and subunits of PRC2 as well as PRC1 are bound to the same regulatory regions of rostral HOXA genes and that they control the differentiation-associated activation of these genes. Furthermore, we find that PRMT6 interacts with subunits of PRC1 and PRC2 and that depletion of PRMT6 results in diminished PRC1/PRC2 and H3K27me3 occupancy and in increased H3K4me3 levels at these target genes. Taken together, our data uncover a novel, additional mechanism of how PRMT6 contributes to gene repression by cooperating with Polycomb proteins. PMID- 26848760 TI - Tocilizumab for treating juvenile idiopathic arthritis. AB - INTRODUCTION: Based on the known relevance of IL-6 in juvenile idiopathic arthritis (JIA) pathophysiology, tocilizumab has been investigated and approved for use in the treatment of systemic and polyarticular JIA. Tocilizumab is a humanized monoclonal antibody that inhibits signaling through both membrane bound and soluble IL-6R. AREAS COVERED: The purpose of this article is to summarize the available clinical data on the efficacy and safety of tocilizumab in JIA and to provide our opinion on the place of tocilizumab in current treatment regimens. A literature search for all relevant clinical trials and studies with regards to tocilizumab, JIA and IL-6 was performed through PubMed, in addition to a review of recent conference abstracts. EXPERT OPINION: Tocilizumab has an important and evolving role in controlling disease activity in patients with JIA. It has proven useful even in patients whose JIA has previously been refractory to other biologic disease modifying anti-rheumatic drugs (DMARDs) and also appears quite effective as monotherapy. Tocilizumab is relatively well tolerated amongst JIA patients, with systemic JIA patients experiencing more serious adverse events overall. PMID- 26848762 TI - [Multiple inappropriate defibrillator shocks due to insulation failure of a Biotronik Linox defibrillator lead with externalized conductor]. AB - In this article the case of a patient who received a total of 35 inappropriate defibrillator shocks due to insulation failure with externalized conductor of a Biotronik Linox(r) lead is described. The implanted defibrillator was immediately inactivated and the failed lead was extracted using a laser sheath system. PMID- 26848761 TI - Adjusted Age-Adjusted Charlson Comorbidity Index Score as a Risk Measure of Perioperative Mortality before Cancer Surgery. AB - BACKGROUND: Identification of patients at risk of death from cancer surgery should aid in preoperative preparation. The purpose of this study is to assess and adjust the age-adjusted Charlson comorbidity index (ACCI) to identify cancer patients with increased risk of perioperative mortality. METHODS: We identified 156,151 patients undergoing surgery for one of the ten common cancers between 2007 and 2011 in the Taiwan National Health Insurance Research Database. Half of the patients were randomly selected, and a multivariate logistic regression analysis was used to develop an adjusted-ACCI score for estimating the risk of 90 day mortality by variables from the original ACCI. The score was validated. The association between the score and perioperative mortality was analyzed. RESULTS: The adjusted-ACCI score yield a better discrimination on mortality after cancer surgery than the original ACCI score, with c-statics of 0.75 versus 0.71. Over 80 years of age, 70-80 years, and renal disease had the strongest impact on mortality, hazard ratios 8.40, 3.63, and 3.09 (P < 0.001), respectively. The overall 90-day mortality rates in the entire cohort varied from 0.9%, 2.9%, 7.0%, and 13.2% in four risk groups stratifying by the adjusted-ACCI score; the adjusted hazard ratio for score 4-7, 8-11, and >= 12 was 2.84, 6.07, and 11.17 (P < 0.001), respectively, in 90-day mortality compared to score 0-3. CONCLUSIONS: The adjusted-ACCI score helps to identify patients with a higher risk of 90-day mortality after cancer surgery. It might be particularly helpful for preoperative evaluation of patients over 80 years of age. PMID- 26848763 TI - Quantifying the benefits of Mediterranean diet in terms of survival. AB - Beneficial effects of Mediterranean diet (MD) have been consistently documented. However, to fully understand the public health implications of MD adherence, an informative step is to quantify these effects in terms of survival time differences. The aim of this study was to evaluate the impact of MD on survival, presenting results in terms of differences in median age at death. We used data from 71,333 participants from a large population-based cohort of Swedish men and women, followed-up between January 1, 1998, and December 31, 2012. A total score of MD, ranging from 0 to 8, was calculated by including information on vegetables and fruits consumption, legumes and nuts, non-refined/high fiber grains, fermented dairy products, fish, red meat, use of olive oil/rapeseed oil, and moderate alcohol intake. Multivariable-adjusted differences in median age at death were estimated with Laplace regression and presented as a function of the MD score. During 15 years of follow-up we documented 14,697 deaths. We observed a linear dose-response association between the MD score and median age at death, with higher score associated with longer survival. The difference in median age at death between participants with the extreme scores (0 vs 8) of MD was up to 2 years (23 months, 95 % CI: 16-29). In this study we documented that adherence to MD may accrue benefits up to 2 years of longer survival. PMID- 26848764 TI - Is Tickling Torture? Assessing Welfare towards Slow Lorises (Nycticebus spp.) within Web 2.0 Videos. AB - Videos, memes and images of pet slow lorises have become increasingly popular on the Internet. Although some video sites allow viewers to tag material as 'animal cruelty', no site has yet acknowledged the presence of cruelty in slow loris videos. We examined 100 online videos to assess whether they violated the 'five freedoms' of animal welfare and whether presence or absence of these conditions contributed to the number of thumbs up and views received by the videos. We found that all 100 videos showed at least 1 condition known as negative for lorises, indicating absence of the necessary freedom; 4% showed only 1 condition, but in nearly one third (31.3%) all 5 chosen criteria were present, including human contact (57%), daylight (87%), signs of stress/ill health (53%), unnatural environment (91%) and isolation from conspecifics (77%). The public were more likely to like videos where a slow loris was kept in the light or displayed signs of stress. Recent work on primates has shown that imagery of primates in a human context can cause viewers to perceive them as less threatened. Prevalence of a positive public opinion of such videos is a real threat towards awareness of the conservation crisis faced by slow lorises. PMID- 26848765 TI - Effect of -55CT Polymorphism of UCP3 on Insulin Resistance and Cardiovascular Risk Factors after a High Protein/Low Carbohydrate versus a Standard Hypocaloric Diet. AB - BACKGROUND: The C/C genotype of a polymorphism in the uncoupling protein3 (UCP3) promoter (-55C->T) (rs1800849) is associated with an increased body mass index. OBJECTIVE: The aim of our study was to investigate the effect of polymorphism on the UCP3 promoter (-55C->T) on insulin resistance and cardiovascular risk factors secondary to a high protein/low carbohydrate vs. a standard hypocaloric diets (1,000 kcal/day). DESIGN: A population of 283 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 9-month period in which subjects received 1 of 2 diets (diet HP: high protein/low carbohydrate vs. diet S: standard diet). RESULTS: Weight improvement was higher in non-T carriers. With both diets and only in wild genotype (diet HP vs. diet S), total cholesterol (-9.7 +/- 4.0 vs. -11.1 +/- 2.0 mg/dl; p > 0.05) and low density lipoprotein (LDL) cholesterol (-8.3 +/- 3.0 vs. 5.5 +/- 2.7 mg/dl; p > 0.05) decreased. The improvement in these parameters was similar in subjects with diet HP than HS. With diet HP and only in wild genotype, glucose (-5.2 +/- 2.2 mg/dl; p < 0.05), triglycerides (-15.5 +/- 3.9 mg/dl; p < 0.05), insulin levels (-3.9 +/- 3.1 UI/l; p < 0.05) and homeostasis model assessment (HOMA-R; -0.6 +/- 0.1 units; p < 0.05) decreased. CONCLUSION: Carriers of T allele have a different response than non-carrier subjects, with a lack of decrease of LDL cholesterol, glucose, insulin levels and HOMA-R. The weight loss was lower in T carriers. HP diet showed a better metabolic response than S diet in 55CC homozygous. PMID- 26848766 TI - Poor patient-reported outcome after hip replacement, related to poor perception of perioperative information, commoner in immigrants than in non-immigrants. AB - Background and purpose - In preparing patients for total hip replacement surgery, providing thorough information helps to reduce anxiety, manage postoperative pain, prevent complications, and better engage patients in their rehabilitation. However, patient characteristics may have an influence on the ability to comprehend and assimilate the information given. We investigated differences in patients born in Sweden and those born outside Sweden regarding how they perceived the information given before THR, and if this was associated with different patient-reported outcomes one year after surgery. Patients and methods From Sahlgrenska University Hospital, we recruited 150 patients born in Sweden and 50 patients born outside Sweden who were to undergo THR. We retrieved routinely collected data from the Swedish Hip Arthroplasty Register including basic demographic variables and patient-reported outcome measures, both preoperatively and at 1-year follow-up. In a separate survey carried out 1-2 weeks after surgery, patients were asked about the information provided in connection with the operation. Results - Patients born outside Sweden more frequently reported that they were poorly informed about possibilities to treat pain and about the operation itself. 1 year after the operation, patients born outside Sweden who, 1-2 weeks after the operation, had reported that they were poorly informed also reported having worse outcomes. Poorer results were found for the questions self-care and anxiety/depression in the EQ-5D questionnaire, pain on a visual analog scale (VAS), EQVAS, and EQ-5D index compared to those patients born in Sweden who had received at least some information of acceptable quality. Interpretation - One quarter of the patients were not satisfied with the information provided before and after THR. These patients more commonly reported perioperative anxiety and they were more often born outside Sweden. Poorly informed patients who had come from countries outside Sweden were more likely to report inferior outcome 1 year after the operation. PMID- 26848767 TI - Guanylate binding protein-1 mediates EGFRvIII and promotes glioblastoma growth in vivo but not in vitro. AB - Glioblastoma multiforme (GBM) is the most common and deadly primary brain tumor in adults. Epidermal growth factor receptor (EGFR) is frequently amplified and mutated in GBM. We previously reported that Guanylate binding protein-1 (GBP1) is a novel transcriptional target gene of EGFR and plays a role in GBM invasion. Here we demonstrate that GBP1 can also be induced by EGFRvIII at the transcriptional level through the p38 MAPK/Yin Yang 1 (YY1) signaling pathway. Silencing of GBP1 by RNA interference significantly inhibits EGFRvIII-mediated GBM cell proliferation in vitro and in a mouse model. Overexpression of GBP1 has no obvious effect on glioblastoma cell proliferation in vitro. In contrast, in an orthotopic glioma mouse model GBP1 overexpression significantly promotes glioma growth and reduces survival rate of glioma-bearing mice by increasing cell proliferation and decreasing cell apoptosis in tumor. Clinically, GBP1 expression is elevated in human GBM tumors and positively correlates with EGFRvIII status in GBM specimens, and its expression is inversely correlated with the survival rate of GBM patients. Taken together, these results reveal that GBP1 may serve as a potential therapeutic target for GBMs with EGFRvIII mutation. PMID- 26848768 TI - Detection rate of actionable mutations in diverse cancers using a biopsy-free (blood) circulating tumor cell DNA assay. AB - Analysis of cell-free DNA using next-generation sequencing (NGS) is a powerful tool for the detection/monitoring of alterations present in circulating tumor DNA (ctDNA). Plasma extracted from 171 patients with a variety of cancers was analyzed for ctDNA (54 genes and copy number variants (CNVs) in three genes (EGFR, ERBB2 and MET)). The most represented cancers were lung (23%), breast (23%), and glioblastoma (19%). Ninety-nine patients (58%) had at least one detectable alteration. The most frequent alterations were TP53 (29.8%), followed by EGFR (17.5%), MET (10.5%), PIK3CA (7%), and NOTCH1 (5.8%). In contrast, of 222 healthy volunteers, only one had an aberration (TP53). Ninety patients with non brain tumors had a discernible aberration (65% of 138 patients; in 70% of non brain tumor patients with an alteration, the anomaly was potentially actionable). Interestingly, nine of 33 patients (27%) with glioblastoma had an alteration (6/33 (18%) potentially actionable). Overall, sixty-nine patients had potentially actionable alterations (40% of total; 69.7% of patients (69/99) with alterations); 68 patients (40% of total; 69% of patients with alterations), by a Food and Drug Administration (FDA) approved drug. In summary, 65% of diverse cancers (as well as 27% of glioblastomas) had detectable ctDNA aberration(s), with the majority theoretically actionable by an approved agent. PMID- 26848769 TI - A fully human CXCR4 antibody demonstrates diagnostic utility and therapeutic efficacy in solid tumor xenografts. AB - For physiologically important cancer therapeutic targets, use of non-invasive imaging for therapeutic guidance and monitoring may improve outcomes for treated patients. The CXC chemokine receptor 4 (CXCR4) is overexpressed in many cancers including non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). CXCR4 overexpression contributes to tumor growth, progression and metastasis. There are several CXCR4-targeted therapeutic agents currently in clinical trials. Since CXCR4 is also crucial for normal biological functions, its prolonged inhibition could lead to unwanted toxicities. While CXCR4-targeted imaging agents and inhibitors have been reported and evaluated independently, there are currently no studies demonstrating CXCR4-targeted imaging for therapeutic guidance. Monoclonal antibodies (mAbs) are commonly used for cancer therapy and imaging. Here, an 89Zr-labeled human CXCR4-mAb (89Zr-CXCR4-mAb) was evaluated for detection of CXCR4 expression with positron emission tomography (PET) while its native unmodified analogue was evaluated for therapy in relevant models of NSCLC and TNBC. In vitro and in vivo evaluation of 89Zr-CXCR4-mAb showed enhanced uptake in NSCLC xenografts with a high expression of CXCR4. It also had the ability to detect lymph node metastases in an experimental model of metastatic TNBC. Treatment of high and low CXCR4 expressing NSCLC and TNBC xenografts with CXCR4-mAb demonstrated a therapeutic response correlating with the expression of CXCR4. Considering the key role of CXCR4 in normal biological functions, our results suggest that combination of 89Zr-CXCR4-mAb-PET with non radiolabeled mAb therapy may provide a precision medicine approach for selecting patients with tumors that are likely to be responsive to this treatment. PMID- 26848770 TI - Genetic evaluation of BRCA1 associated a complex genes with triple-negative breast cancer susceptibility in Chinese women. AB - BACKGROUND: The tumor suppressor BRCA1 plays a pivotal role in maintaining genomic stability and tumor suppression. The BRCA1-A complex is required for recruitment of BRCA1 to DNA damage sites, DNA repair and cell cycle checkpoint control. Since germline mutations of BRCA1 often lead to breast tumors that are triple-negative breast cancer (TNBC) type, we aimed to investigate whether genetic deficiency in genes of the BRCA1-A complex is associated with risk to TNBC development. RESULTS: We found that rs7250266 in the promoter region of NBA1 confers a decreased risk to TNBC development, but not to non-TNBC susceptibility. In addition, the haplotypes containing two polymorphisms rs7250266 and rs2278256 are associated with a lower chance of TNBC development specifically. Our studies also showed that the protective alleles of rs7250266 (C > G) and rs2278256 (T > C) down-regulate promoter activity of NBA1 in mammary epithelial cells. METHODS: We investigated associations between the BRCA1-A complex genes and TNBC developing risk in first case-control study of Chinese Han Women population including 414 patients with TNBC and 354 cancer-free controls. We detected 37 common variants in ABRAXAS, RAP80, BRE, BRCC36 and NBA1/MERIT40 genes encoding the BRCA1-A complex and evaluated their genetic susceptibility to the risk of TNBC. An additional cohort with 652 other types of breast cancer (non-TNBC) cases and 890 controls was used to investigate the associations between TNBC-specific SNPs genotype and non-TNBCs susceptibility. CONCLUSIONS: Genetic variants in NBA1 may be an important genetic determinant of TNBC susceptibility. Further investigation and validation of these SNPs in larger cohorts may facilitate in predication and prevention of TNBC and in counseling individuals for risk of TNBC development. PMID- 26848771 TI - Preclinical evaluation of a nanoformulated antihelminthic, niclosamide, in ovarian cancer. AB - Ovarian cancer treatment remains a challenge and targeting cancer stem cells presents a promising strategy. Niclosamide is an "old" antihelminthic drug that uncouples mitochondria of intestinal parasites. Although recent studies demonstrated that niclosamide could be a potential anticancer agent, its poor water solubility needs to be overcome before further preclinical and clinical investigations can be conducted. Therefore, we evaluated a novel nanosuspension of niclosamide (nano-NI) for its effect against ovarian cancer. Nano-NI effectively inhibited the growth of ovarian cancer cells in which it induced a metabolic shift to glycolysis at a concentration of less than 3 MUM in vitro and suppressed tumor growth without obvious toxicity at an oral dose of 100 mg/kg in vivo. In a pharmacokinetic study after oral administration, nano-NI showed rapid absorption (reaching the maximum plasma concentration within 5 min) and improved the bioavailability (the estimated bioavailability for oral nano-NI was 25%). In conclusion, nano-NI has the potential to be a new treatment modality for ovarian cancer and, therefore, further clinical trials are warranted. PMID- 26848772 TI - Identification of cis- and trans-acting elements regulating calretinin expression in mesothelioma cells. AB - Calretinin (CALB2) is a diagnostic marker for epithelioid mesothelioma. It is also a prognostic marker since patients with tumors expressing high calretinin levels have better overall survival. Silencing of calretinin decreases viability of epithelioid mesothelioma cells. Our aim was to elucidate mechanisms regulating calretinin expression in mesothelioma. Analysis of calretinin transcript and protein suggested a control at the mRNA level. Treatment with 5-aza-2' deoxycytidine and analysis of TCGA data indicated that promoter methylation is not likely to be involved. Therefore, we investigated CALB2 promoter by analyzing ~1kb of genomic sequence surrounding the transcription start site (TSS) + 1 using promoter reporter assay. Deletion analysis of CALB2 proximal promoter showed that sequence spanning the -161/+80bp region sustained transcriptional activity. Site directed analysis identified important cis-regulatory elements within this 161/+80bp CALB2 promoter. EMSA and ChIP assays confirmed binding of NRF-1 and E2F2 to the CALB2 promoter and siRNA knockdown of NRF-1 led to decreased expression of calretinin. Cell synchronization experiment showed that calretinin expression was cell cycle regulated with a peak of expression at G1/S phase. This study provides the first insight in the regulation of CALB2 expression in mesothelioma cells. PMID- 26848773 TI - Long-term prognostic implications and therapeutic target role of hexokinase II in patients with nasopharyngeal carcinoma. AB - Tumor cells preferentially use anaerobic glycolysis rather than oxidative phosphorylation to generate energy. Hexokinase II (HK-II) is necessary for anaerobic glycolysis and displays aberrant expression in malignant cells. The current study aimed to evaluate the role of HK-II in the survival and biological function of nasopharyngeal carcinoma (NPC). Our study demonstrated that high expression of HK-II was associated with poor survival outcomes in NPC patients. When using 3-BrOP (an HK-II inhibitor) to repress glycolysis, cell proliferation and invasion were attenuated, accompanied by the induction of apoptosis and cell cycle arrest at the G1 stage. Furthermore, 3-BrOP synergized with cisplatin (DDP) to induce NPC cell death. Collectively, we provided that the aberrant expression of HK-II was associated with the malignant phenotype of NPC. A combined treatment modality that targets glycolysis with DDP holds promise for the treatment of NPC patients. PMID- 26848774 TI - MicroRNA-223 and microRNA-92a in stool and plasma samples act as complementary biomarkers to increase colorectal cancer detection. AB - Aberrant levels of circulating miRNAs are potential biomarkers for the early detection of colorectal cancer (CRC). However, no previous systematic study has examined miRNAs in various specimen types from the same patient to evaluate their clinical utility. In this study, we compiled information from ~450 articles published before 2012, and selected the 46 most frequently reported CRC-related miRNAs as candidates. We then established a 46-miRNA multiplex RT-qPCR method, and efficiently examined two clinically accessible samples: stool from fecal occult blood test and EDTA plasma. A total of 62 tissue, 447 stool, and 398 plasma samples were collected from CRC patients and healthy controls. Good correlations of detectable miRNAs were noticed in paired tumor tissues, stool, and plasma samples of 62 CRC patients. Using these 62 CRC patients and 62 matched healthy controls as the training set, 5 and 11 differentially expressed miRNAs achieved the area under the ROC curve (AUC) greater than 0.7 in stool and plasma samples, respectively. The selected miRNAs was subsequently validated using the remaining enrolled samples as the test cohort; 4 miRNAs in stool and 6 miRNAs in plasma were maintained discriminating powers for CRC patients. After examining the complementary effect, combined analysis of miR-223 and miR-92a, which were commonly present in stool and plasma samples, yielded the highest sensitivity of 96.8% and the specificity of 75% for CRC (AUC = 0.907). These results allowed us to establish a two-miRNA biosignature in two types of CRC clinical specimens with a high sensitivity for CRC detection. PMID- 26848778 TI - Cationized gelatin hydrogels mixed with plasmid DNA induce stronger and more sustained gene expression than atelocollagen at calvarial bone defects in vivo. AB - Gene transduction of exogenous factors at local sites in vivo is a promising approach to promote regeneration of tissue defects owing to its simplicity and capacity for expression of a variety of genes. Gene transduction by viral vectors is highly efficient; however, there are safety concerns associated with viruses. As a method for nonviral gene transduction, plasmid DNA delivery is safer and simpler, but requires an efficient carrier substance. Here, we aimed to develop a simple, efficient method for bone regeneration by gene transduction and to identify optimal conditions for plasmid DNA delivery at bone defect sites. We focused on carrier substances and compared the efficiencies of two collagen derivatives, atelocollagen, and gelatin hydrogel, as substrates for plasmid DNA delivery in vivo. To assess the efficiencies of these substrates, we examined exogenous expression of green fluorescence protein (GFP) by fluorescence microscopy, polymerase chain reaction, and immunohistochemistry. GFP expression at the bone defect site was higher when gelatin hydrogel was used as a substrate to deliver plasmids than when atelocollagen was used. Moreover, the gelatin hydrogel was almost completely absorbed at the defect site, whereas some atelocollagen remained. When a plasmid harboring bone morphogenic protein 2 was delivered with the substrate to bony defect sites, more new bone formation was observed in the gelatin group than in the atelocollagen group. These results suggested that the gelatin hydrogel was more efficient than atelocollagen as a substrate for local gene delivery and may be a superior material for induction of bone regeneration. PMID- 26848779 TI - CARM1 Preferentially Methylates H3R17 over H3R26 through a Random Kinetic Mechanism. AB - CARM1 is a type I arginine methyltransferase involved in the regulation of transcription, pre-mRNA splicing, cell cycle progression, and the DNA damage response. CARM1 overexpression has been implicated in breast, prostate, and liver cancers and therefore is an attractive target for cancer therapy. To date, little about the kinetic properties of CARM1 is known. In this study, substrate specificity and the kinetic mechanism of the human enzyme were determined. Substrate specificity was examined by testing CARM1 activity with several histone H3-based peptides in a radiometric assay. Comparison of kcat/KM values reveals that methylation of H3R17 is preferred over that of H3R26. These effects are KM driven as kcat values remain relatively constant for the peptides tested. Shortening the peptide at the C-terminus by five amino acid residues greatly reduced binding affinity, indicating distal residues may contribute to substrate binding. CARM1 appears to bind monomethylated peptides with an affinity similar to that of unmethylated peptides. Monitoring of the CARM1-dependent production of monomethylated and dimethylated peptides over time by self-assembled monolayer and matrix-assisted laser desorption ionization mass spectrometry revealed that methylation by CARM1 is distributive. Additionally, dead-end and product inhibition studies suggest CARM1 conforms to a random sequential kinetic mechanism. By defining the kinetic properties and mechanism of CARM1, these studies may aid in the development of small molecule CARM1 inhibitors. PMID- 26848780 TI - The effects of ordinal load on incidental temporal learning. AB - How can we grasp the temporal structure of events? A few studies have indicated that representations of temporal structure are acquired when there is an intention to learn, but not when learning is incidental. Response-to-stimulus intervals, uncorrelated temporal structures, unpredictable ordinal information, and lack of metrical organization have been pointed out as key obstacles to incidental temporal learning, but the literature includes piecemeal demonstrations of learning under all these circumstances. We suggest that the unacknowledged effects of ordinal load may help reconcile these conflicting findings, ordinal load referring to the cost of identifying the sequence of events (e.g., tones, locations) where a temporal pattern is embedded. In a first experiment, we manipulated ordinal load into simple and complex levels. Participants learned ordinal-simple sequences, despite their uncorrelated temporal structure and lack of metrical organization. They did not learn ordinal complex sequences, even though there were no response-to-stimulus intervals nor unpredictable ordinal information. In a second experiment, we probed learning of ordinal-complex sequences with strong metrical organization, and again there was no learning. We conclude that ordinal load is a key obstacle to incidental temporal learning. Further analyses showed that the effect of ordinal load is to mask the expression of temporal knowledge, rather than to prevent learning. PMID- 26848776 TI - A targeted genetic association study of epithelial ovarian cancer susceptibility. AB - BACKGROUND: Genome-wide association studies have identified several common susceptibility alleles for epithelial ovarian cancer (EOC). To further understand EOC susceptibility, we examined previously ungenotyped candidate variants, including uncommon variants and those residing within known susceptibility loci. RESULTS: At nine of eleven previously published EOC susceptibility regions (2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13), novel variants were identified that were more strongly associated with risk than previously reported variants. Beyond known susceptibility regions, no variants were found to be associated with EOC risk at genome-wide statistical significance (p <5x10(-8)), nor were any significant after Bonferroni correction for 17,000 variants (p< 3x10 6). METHODS: A customized genotyping array was used to assess over 17,000 variants in coding, non-coding, regulatory, and known susceptibility regions in 4,973 EOC cases and 5,640 controls from 13 independent studies. Susceptibility for EOC overall and for select histotypes was evaluated using logistic regression adjusted for age, study site, and population substructure. CONCLUSION: Given the novel variants identified within the 2q31, 3q25, 5p15, 8q21, 8q24, 10p12, 17q12, 17q21.31, and 19p13 regions, larger follow-up genotyping studies, using imputation where necessary, are needed for fine-mapping and confirmation of low frequency variants that fall below statistical significance. PMID- 26848775 TI - Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants. AB - Trisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue--obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT)--and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) and the interactions between all the system's constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the "canonical" way of thymus functioning. Conversely, DS networks represent a "non canonical" way, i.e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probably driven by epigenetic mechanisms acting at chromatin level and through the miRNA control of transcriptional programs involving the networks' high-hierarchy genes. PMID- 26848777 TI - Oblongifolin M, an active compound isolated from a Chinese medical herb Garcinia oblongifolia, potently inhibits enterovirus 71 reproduction through downregulation of ERp57. AB - There is no effective drug to treat EV71 infection yet. Traditional Chinese herbs are great resources for novel antiviral compounds. Here we showed that Oblongifolin M (OM), an active compound isolated from Garcinia oblongifolia, potently inhibited EV71 infection in a dose dependent manner. To identify its potential effectors in the host cells, we successfully identified 18 proteins from 52 differentially expressed spots by comparative proteomics studies. Further studies showed that knockdown of ERp57 inhibited viral replication through downregulating viral IRES (internal ribosome entry site) activities, whereas ectopic expression of ERp57 increased IRES activity and partly rescued the inhibitory effects of OM on viral replication. We demonstrated that OM is an effective antiviral agent; and that ERp57 is one of its cellular effectors against EV71 infection. PMID- 26848781 TI - Serum cartilage oligomeric matrix protein and development of radiographic and painful knee osteoarthritis. A community-based cohort of middle-aged women. AB - CONTEXT AND OBJECTIVE: We evaluated the predictive value of serum cartilage oligomeric matrix protein (sCOMP) levels over 20 years on the development of radiographic (RKOA) and painful knee osteoarthritis (KOA) in a longitudinal cohort of middle-aged women. MATERIALS AND METHODS: Five hundred and ninety-three women with no baseline KOA underwent 5-year knee radiographs over 20-years and were asked about knee pain a month before each assessment. A repeated measures logistic regression model was used where the outcomes were recorded at 5, 10, 15 and 20-years follow-up. RESULTS: The highest quartile of sCOMP was associated with increased risk of RKOA with overall OR of 1.97 (95% CI: 1.33-2.91) over 20 years when compared with the lowest sCOMP quartile. The association with painful KOA was similar and also independent, but only when the fourth and third sCOMP quartiles were compared. DISCUSSION AND CONCLUSION: This study demonstrates that sCOMP levels are predictive of subsequent structural changes and incidence of painful KOA, independently of age and BMI. PMID- 26848782 TI - Optical fiber-based full Mueller polarimeter for endoscopic imaging using a two wavelength simultaneous measurement method. AB - This paper reports a technique based on spectrally differential measurement for determining the full Mueller matrix of a biological sample through an optical fiber. In this technique, two close wavelengths were used simultaneously, one for characterizing the fiber and the other for characterizing the assembly of fiber and sample. The characteristics of the fiber measured at one wavelength were used to decouple its contribution from the measurement on the assembly of fiber and sample and then to extract sample Mueller matrix at the second wavelength. The proof of concept was experimentally validated by measuring polarimetric parameters of various calibrated optical components through the optical fiber. Then, polarimetric images of histological cuts of human colon tissues were measured, and retardance, diattenuation, and orientation of the main axes of fibrillar regions were displayed. Finally, these images were successfully compared with images obtained by a free space Mueller microscope. As the reported method does not use any moving component, it offers attractive integration possibilities with an endoscopic probe. PMID- 26848784 TI - Ultrafast and nonlinear surface-enhanced Raman spectroscopy. AB - Ultrafast surface-enhanced Raman spectroscopy (SERS) has the potential to study molecular dynamics near plasmonic surfaces to better understand plasmon-mediated chemical reactions such as plasmonically-enhanced photocatalytic or photovoltaic processes. This review discusses the combination of ultrafast Raman spectroscopic techniques with plasmonic substrates for high temporal resolution, high sensitivity, and high spatial resolution vibrational spectroscopy. First, we introduce background information relevant to ultrafast SERS: the mechanisms of surface enhancement in Raman scattering, the characterization of plasmonic materials with ultrafast techniques, and early complementary techniques to study molecule-plasmon interactions. We then discuss recent advances in surface enhanced Raman spectroscopies with ultrafast pulses with a focus on the study of molecule-plasmon coupling and molecular dynamics with high sensitivity. We also highlight the challenges faced by this field by the potential damage caused by concentrated, highly energetic pulsed fields in plasmonic hotspots, and finally the potential for future ultrafast SERS studies. PMID- 26848783 TI - Room-Temperature Creation and Spin-Orbit Torque Manipulation of Skyrmions in Thin Films with Engineered Asymmetry. AB - Magnetic skyrmions, which are topologically protected spin textures, are promising candidates for ultralow-energy and ultrahigh-density magnetic data storage and computing applications. To date, most experiments on skyrmions have been carried out at low temperatures. The choice of available materials is limited, and there is a lack of electrical means to control skyrmions in devices. In this work, we demonstrate a new method for creating a stable skyrmion bubble phase in the CoFeB-MgO material system at room temperature, by engineering the interfacial perpendicular magnetic anisotropy of the ferromagnetic layer. Importantly, we also demonstrate that artificially engineered symmetry breaking gives rise to a force acting on the skyrmions, in addition to the current-induced spin-orbit torque, which can be used to drive their motion. This room-temperature creation and manipulation of skyrmions offers new possibilities to engineer skyrmionic devices. The results bring skyrmionic memory and logic concepts closer to realization in industrially relevant and manufacturable thin film material systems. PMID- 26848786 TI - The promise of gene therapy. AB - PURPOSE OF REVIEW: The promise of gene therapy performed in the preimplantation and prenatal periods of pregnancy is rapidly becoming a reality. New technologies capable of making designed changes in single nucleotides make germline gene therapy possible. The article reviews the ethical and technical challenges of germline gene therapy. RECENT FINDINGS: Clustered regularly interspaced short palindromic repeats and related technologies are capable of deleting and inserting specific DNA sequences in mutated genes so as to correct the targeted DNA. The ability to target specific gene mutations will offer unique opportunities to at risk families, particularly those whose genotypes prevent any chance of a normal pregnancy outcome. Other applications of gene-modifying technologies on gametes, zygotes, and embryos are likely in the near future. SUMMARY: There will be renewed debates on the potentially controversial applications of these technologies because of their capability to genetically alter the human germline and thereby future generations. PMID- 26848787 TI - Aspiration Pneumonia: An Underappreciated Risk of Clozapine Treatment. PMID- 26848789 TI - Sustained Hyperparathyroidism Among Patients Treated With Lithium. PMID- 26848785 TI - Lysyl Oxidase Isoforms and Potential Therapeutic Opportunities for Fibrosis and Cancer. AB - INTRODUCTION: The lysyl oxidase family of enzymes is classically known as being required for connective tissue maturation by oxidizing lysine residues in elastin and lysine and hydroxylysine residues in collagen precursors. The resulting aldehydes then participate in cross-link formation, which is required for normal connective tissue integrity. These enzymes have biological functions that extend beyond this fundamental biosynthetic role, with contributions to angiogenesis, cell proliferation, and cell differentiation. Dysregulation of lysyl oxidases occurs in multiple pathologies including fibrosis, primary and metastatic cancers, and complications of diabetes in a variety of tissues. AREAS COVERED: This review summarizes the major findings of novel roles for lysyl oxidases in pathologies, and highlights some of the potential therapeutic approaches that are in development and which stem from these new findings. EXPERT OPINION: Fundamental questions remain regarding the mechanisms of novel biological functions of this family of proteins, and regarding functions that are independent of their catalytic enzyme activity. However, progress is underway in the development of isoform-specific pharmacologic inhibitors, potential therapeutic antibodies and gaining an increased understanding of both tumor suppressor and metastasis promotion activities. Ultimately, this is likely to lead to novel therapeutic agents. PMID- 26848788 TI - Interaction of Dopamine D2 and 5-HT1A Receptor Partial Agonism on Antipsychotic Efficacy. PMID- 26848790 TI - Necrotizing Pneumonia in the Setting of Elevated Clozapine Levels. PMID- 26848791 TI - Symptom Severity and the Generalizability of Antidepressant Efficacy Trials: Changes During the Past 20 Years. AB - The most commonly used inclusion/exclusion criterion in antidepressant efficacy trials (AETs) is a minimum score on a symptom severity scale. In the present study, we reviewed placebo-controlled AETs published during the past 20 years to determine whether there has been a change in the symptom severity inclusion criterion threshold subsequent to publications that highlighted the unrepresentativeness of the depressed patients studied in AETs. We identified 170 AETs published during the past 20 years and compared the studies published during the past 5 years (2010-2104, n = 56) with the studies published during the previous 15 years (n = 114). The symptom severity threshold for inclusion has increased in the more recent cohort of studies. On the 17-item Hamilton Depression Rating Scale, almost half of the studies of the past 5 years used a cutoff of 22 or greater to select patients versus less than one-fifth of the studies during the previous 15 years (44.0% vs 17.5%; chi(2) = 7.4; P < 0.01). Similarly, the cutoff on the Montgomery-Asberg Depression Rating Scale required for study inclusion has been higher in studies of the past 5 years with approximately three-quarters of the recent studies using a cutoff of at least 25, in contrast to one-quarter of the older studies (76.2% vs 25.0%; chi(2) = 8.2; P < 0.01). A significantly higher percentage of patients in our clinical practice would be excluded on the basis of the severity thresholds of the past 5 years (59.3 +/- 13.5 vs 49.0 +/- 15.1; t121 = 3.1; P < 0.005). These findings suggest that the results of AETs may not be applicable to less severely depressed patients who make up at least half of the patients treated in routine clinical practice. Questions are raised about the Food and Drug Administration labeling of antidepressants. PMID- 26848792 TI - Extrapyramidal Symptoms During Risperidone Maintenance Treatment in Schizophrenia: A Prospective, Multicenter Study. AB - The risperidone maintenance treatment in schizophrenia study was designed to identify the duration of maintenance treatment required with an initial therapeutic dose in contrast to reducing the dose over time. This study investigated extrapyramidal symptoms (EPSs) in different risperidone maintenance treatment paradigms over 1 year. Clinically stabilized patients with schizophrenia (n = 374) were randomized to a no-dose-reduction group and 4-week and 26-week reduction groups, in which the dose was gradually reduced by 50% over 8 weeks and maintained. Extrapyramidal symptoms were assessed at baseline and monthly for 6 months, followed by every 2 months. The Simpson-Angus Scale of Extrapyramidal Symptoms-Chinese version assessed EPS severity. Data were analyzed by a generalized linear mixed model (GLMM). The frequency of EPS at baseline was 23.2%, 20.0%, and 21.3% in the 4-week, 26-week, and no-dose-reduction groups, respectively. Risperidone dosage, positive symptoms, and disorganized thoughts at baseline predicted development of EPS. The GLMM indicated that a significant decrease in EPS was maintained, and different trajectories occurred over time across groups. In the 235 patients who continued treatment after 1 year, the incidence of EPS decreased to 4.1%, 2.8%, and 10.0% in the 4-week, 26-week, and no-dose-reduction groups, respectively, whereas the numbers of dropouts because of intolerable EPS were not significantly different (4.8%, 6.7%, and 6.2%, respectively). These novel findings indicate EPSs were tolerable and differentially decreased depending on the dose paradigm during the 1-year treatment period. Future studies should implement a GLMM to investigate antipsychotic adverse effects during long-term treatment. PMID- 26848793 TI - Asymptomatic Elevation of Amylase and Lipase After Olanzapine Treatment. PMID- 26848794 TI - Quantitative and semi-quantitative histopathological examination of renal biopsies in healthy individuals, and associations with kidney function. AB - This study assesed the prevalence of histopathological changes in renal biopsies from healthy individuals, and the association with age, sex and smoking. Donor biopsies from 109 subjects were obtained from living kidney donors, and blood and urine samples were collected together with medical history. All biopsies were scored according to the Banff '97 classification with some modifications. The parameters included in this study were tubular atrophy, interstitial fibrosis, glomerulosclerosis, arteriosclerosis, arteriolohyalinosis and a sclerosis score. An alternative scoring system for tubular atrophy was examined (using <=5% rather than <1% as a cut-off for grade 0). Glomerular filtration rate was measured in most cases as chromium ethylenediaminetetra-acetic acid (Cr-EDTA) clearance. Age was a significant predictor for tubular atrophy, fibrosis and sclerosis. Pack years of smoking increased the risk of tubular atrophy, fibrosis and arteriolohyalinosis. The alternative scoring of tubular atrophy showed a stronger association with smoking, but a weaker association with age, compared with the original one. Limited histopathological changes are common in healthy kidney donors around 50 years of age with normal kidney function. We propose that a cut off of <=5% yields a better definition of grade 0 tubular atrophy compared with the established cut-off of >0%. PMID- 26848795 TI - Aquaporin 1 protein expression is associated with BRAF V600 mutation and adverse prognosis in cutaneous melanoma. AB - Despite experimental findings suggesting the prognostic significance of Aquaporin 1 (AQP1) in human melanoma, no published clinical data are available. We studied the expression of AQP1 protein in cutaneous melanoma, correlated our findings with standard histological and genetic markers, and long-term clinical follow-up. Our study evaluated the AQP1 protein expression in 78 melanoma patients, representing two predefined risk cohorts using the immune labeling technique with commercially available anti-AQP1 antibodies on routinely formalin-fixed and paraffin-embedded tumor tissue samples. BRAF V600E mutation analyses were carried out successfully in 70 patients using PCR and restriction fragment length polymorphism analyses, followed by confirmatory analysis with the Sanger sequencing technique. AQP1-expressing melanoma cells were found in 52 cases (66.7%, median H-score=124.24). Significantly higher AQP1 H-scores (P=0.047) were found in the 'high-risk' patients. No correlations were found with the established histological markers, such as mitotic index (P=0.42), Clark level (P=0.95), and Breslow thickness (P=0.51). BRAF V600 mutation analyses were successful in 89%, and showed a two times higher mutation frequency in the 'high risk' group. The BRAF V600 mutations were significantly associated with AQP1 expression (P=0.014). Long-term follow-up indicated a reduced progression-free survival (P=0.036) and overall survival (P=0.017) for the AQP1-positive cutaneous melanoma patients. AQP1 expression is likely to be associated with an adverse prognosis in cutaneous melanoma. PMID- 26848796 TI - The use of pembrolizumab for the treatment of metastatic uveal melanoma. AB - Uveal melanoma is a rare type of melanoma, with only five to seven cases per one million persons diagnosed each year. Patients with metastatic melanoma of uveal origin tend to have lower response rates on traditional therapies. Herein we report our experience with 10 patients with metastatic uveal melanoma (MUM) who received pembrolizumab. Eligible patients were more than or equal to 18 years old, had unresectable MUM, progressed on prior ipilimumab therapy, had good performance status (Eastern Cooperative Oncology Group of 0 or 1), and adequate organ and marrow function. Patients could have central nervous system disease, but needed to be clinically stable. Patients were treated with 2 mg/kg pembrolizumab intravenously over 30 min every 3 weeks until disease progression, unacceptable toxicity, or for up to 2 years. Between April 2014 and October 2014, we treated a total of 10 patients with MUM with pembrolizumab. Median age was 65 years, with 70% being female. As of the data cutoff date of 14 May 2015, median progression-free survival was 18 weeks (range 3.14-49.3 weeks), with four patients still currently receiving therapy. Of eight evaluable patients, there was one complete response, two partial responses, and one patient with stable disease. Four patients had rapidly progressive disease. Toxicities were as expected and were usually grade 1/2 in nature. Although this cohort of patients was small, to our knowledge this is the first such report of outcomes in uveal melanoma patients being treated with anti-PD1 therapy. In the absence of a clinical trial, treatment with pembrolizumab appears to be a viable option for patients with MUM. PMID- 26848798 TI - IgG Subclass Staining in Routine Renal Biopsy Material. AB - Immunofluorescence staining plays a vital role in nephropathology, but the panel of antibodies used has not changed for decades. Further classification of immunoglobulin (Ig)G-containing immune-type deposits with IgG subclass staining (IgG1, IgG2, IgG3, and IgG4) has been shown to be of diagnostic utility in glomerular diseases, but their value in the evaluation of renal biopsies has not been addressed systematically in large renal biopsy material. Between January 2007 and June 2014, using direct immunofluorescence, we stained every renal biopsy for the IgG subclasses if there was moderate to prominent glomerular IgG staining and/or IgG-predominant or IgG-codominant glomerular staining. The total number of biopsies stained was 1084, which included 367 cases of membranous glomerulonephritis, 307 cases of lupus nephritis, 74 cases of fibrillary glomerulonephritis, 53 cases of proliferative glomerulonephritis with monoclonal IgG deposits, and 25 cases of antiglomerular basement membrane disease, among others. We found that monoclonality of IgG deposits cannot always be reliably determined on the basis of kappa and lambda light chain staining alone, particularly if concomitant (frequently nonspecific) IgM staining is present. In IgG heavy and heavy and light chain deposition disease (3 cases), subclass staining is very helpful, and in proliferative glomerulonephritis with monoclonal IgG deposits subclass staining is necessary. IgG subclass staining is useful in differentiating primary from secondary membranous glomerulonephritis. In proliferative glomerulonephritis with polyclonal IgG deposition, IgG1 dominance/codominance with concomitant IgG3 and IgG2 but weak or absent IgG4 staining favors an underlying autoimmune disease. IgG subclass staining is a very useful diagnostic method in a selected cohort of renal biopsies, particularly in biopsies with glomerulonephritis with monoclonal IgG deposits. PMID- 26848797 TI - Isolated Loss of PMS2 Immunohistochemical Expression is Frequently Caused by Heterogenous MLH1 Promoter Hypermethylation in Lynch Syndrome Screening for Endometrial Cancer Patients. AB - Lynch syndrome (LS) is an autosomal-dominant inherited disorder mainly caused by a germline mutation in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) and is associated with increased risk for various cancers, particularly colorectal cancer and endometrial cancer (EC). Women with LS account for 2% to 6% of EC patients; it is clinically important to identify LS in such individuals for predicting and/or preventing additional LS-associated cancers. PMS2 germline mutation (PMS2-LS) is the rarest contribution to LS etiology among the 4 LS associated MMR germline mutations, and its detection is complicated. Therefore, prudent screening for PMS2-LS is important as it leads to an efficient LS identification strategy. Immunohistochemistry is recommended as a screening method for LS in EC. Isolated loss of PMS2 (IL-PMS2) expression is caused not only by PMS2-LS but also by MLH1 germline mutation or MLH1 promoter hypermethylation (MLH-PHM). This study aimed to determine the association between MLH1-PHM and IL-PMS2 to avoid inappropriate genetic analysis. We performed MLH1 methylation analysis and MLH1/PMS2 germline mutation testing on the IL-PMS2 cases. By performing MMR-immunohistochemistry on 360 unselected ECs, we could select 8 (2.2%) cases as IL-PMS2. Heterogenous MLH1 staining and MLH1-PHM were detected in 4 of 8 (50%) IL-PMS2 tumors. Of the 5 IL-PMS2 patients who underwent genetic analysis, 1 had PMS2 germline mutation with normal MLH1 expression (without MLH1-PHM), and no MLH1 germline mutation was detected. We suggest that MLH1 promoter methylation analysis for IL-PMS2 EC should be performed to exclude sporadic cases before further PMS2 genetic testing. PMID- 26848799 TI - Clear Cell Carcinoma of the Penis: An HPV-related Variant of Squamous Cell Carcinoma: A Report of 3 Cases. AB - Penile clear cell carcinoma originating in skin adnexal glands has been previously reported. Here, we present 3 morphologically distinctive penile tumors with prominent clear cell features originating not in the penile skin but in the mucosal tissues of the glans surface squamous epithelium. Clinical and pathologic features were evaluated. Immunohistochemical stains were GATA3 and p16. Human papilloma virus (HPV) detection by in situ hybridization was performed in 3 cases, and whole-tissue section-polymerase chain reaction was performed in 1 case. Patients' ages were 52, 88, and 95 years. Tumors were large and involved the glans and coronal sulcus in all cases. Microscopically, nonkeratinizing clear cells predominated. Growth was in solid nests with comedo-like or geographic necrosis. Focal areas of invasive warty or basaloid carcinomas showing in addition warty or basaloid penile intraepithelial neoplasia were present in 2 cases. There was invasion of corpora cavernosa, lymphatic vessels, veins, and perineural spaces in all cases. p16 was positive, and GATA3 stain was negative in the 3 cases. HPV was detected in 3 cases by in situ hybridization and in 1 case by polymerase chain reaction. Differential diagnoses included other HPV-related penile carcinomas, skin adnexal tumors, and metastatic renal cell carcinoma. Features that support primary penile carcinoma were tumor location, concomitant warty and/or basaloid penile intraepithelial neoplasia, and HPV positivity. Clinical groin metastases were present in all cases, pathologically confirmed in 1. Two patients died from tumor dissemination at 9 and 12 months after penectomy. Clear cell carcinoma, another morphologic variant related to HPV, originates in the penile mucosal surface and is probably related to warty carcinomas. PMID- 26848800 TI - Two Cases of Renal Cell Carcinoma Harboring a Novel STRN-ALK Fusion Gene. AB - Anaplastic lymphoma kinase (ALK) translocation renal cell carcinomas (RCCs) have been reported by several independent groups in recent times. The clinical behavior and histopathologic characteristics of these carcinomas are not fully understood because of the paucity of cases reported. Here, we describe 2 cases of RCC harboring a novel striatin (STRN)-ALK fusion. The first case was a 33-year old woman with no sickle cell trait who underwent nephrectomy for right renal mass and had late recurrence in para-aortic lymph nodes twice 10 and 12 years after initial surgery. After the second recurrence, she was carefully observed without any treatment. Twenty-six years after the initial nephrectomy, the second para-aortic lymphadenectomy was performed, and gastrectomy was performed for newly developed primary gastric cancer. The resected para-aortic lymph nodes were largely replaced by metastatic carcinoma. The second case was a 38-year-old man with no sickle cell trait who underwent cytoreductive nephrectomy followed by sunitinib therapy for metastatic RCC. In both cases, the tumor showed solid, papillary, tubular, and mucinous cribriform structures. Psammoma bodies were occasionally seen in the stroma. Tumor cells had a large nucleus and prominent nucleoli with predominantly eosinophilic cytoplasm. Rhabdoid cells and signet ring cells were also observed. Intracytoplasmic mucin deposition and background mucinous stroma were confirmed. In the second case, tumor necrosis was seen in some areas. Tumor cells exhibited diffuse positive staining for ALK in both cases. ALK translocation was confirmed by fluorescent in situ hybridization, and further gene analysis revealed a STRN-ALK fusion. These cases provide great insights into ALK translocation RCCs. PMID- 26848801 TI - Differential Diagnosis of Intraductal Lesions of the Prostate. AB - The category of intraductal lesions of the prostate includes a range of primary prostatic and nonprostatic processes with wide variation in prognosis and recommended follow-up. Studies have shown that pathologists are uncomfortable with the diagnosis of these lesions and that the diagnostic reproducibility is low in this category. Despite the diagnostic difficulty, their accurate and reproducible diagnosis is critical for patient management. This review aims to highlight the diagnostic criteria, prognosis, and treatment implications of common intraductal lesions of the prostate. It focuses on the recognition of intraductal carcinoma of the prostate (IDC-P) in prostate needle biopsies and how to distinguish it from its common mimickers, including high-grade prostatic intraepithelial neoplasia, invasive cribriform prostatic adenocarcinoma, urothelial carcinoma extending into prostatic ducts, and prostatic ductal adenocarcinoma. IDC-P is independently associated with higher risk disease, and its identification in a needle biopsy, even in the absence of invasive carcinoma, should compel definitive treatment. Conversely, high-grade prostatic intraepithelial neoplasia has a much better prognosis and in limited quantities does not even warrant a repeat biopsy. IDC-P must be distinguished from urothelial carcinoma involving prostatic ducts, as recommended treatment varies markedly. Ductal adenocarcinoma may confuse the pathologist and clinician by overlapping terminology, and morphology may also mimic IDC-P on occasion. The use of ancillary testing with immunohistochemistry and molecular markers has also been reviewed. PMID- 26848802 TI - The Natural Substance MS-10 Improves and Prevents Menopausal Symptoms, Including Colpoxerosis, in Clinical Research. AB - Many natural substances were screened to develop nutraceuticals that reduce menopausal symptoms. A complex of Cirsium japonicum var. maackii and Thymus vulgaris extracts, named MS-10, had significant positive effects. Under a low concentration of estrogen, which represents postmenopausal physiological conditions, MS-10 had beneficial effects on estrogen receptor-expressing MCF-7 cells by reversibly enhancing estrogen activity. In addition, in the ovariectomized rat model, changes in bone-specific alkaline phosphatase activity and osteocalcin, as well as low-density lipoprotein cholesterol and triglyceride levels were significantly decreased by MS-10. These results show that MS-10 protected bone health and reduced metabolic disturbances. Furthermore, in a clinical study, all menopausal symptoms, including hot flushes, parenthesis, insomnia, nervousness, melancholia, vertigo, fatigue, rheumatic pain, palpitations, formication, and headache, as well as colpoxerosis, were significantly improved by taking MS-10 for 90 days. Therefore, the evidence supports that MS-10 is an effective natural substance that can safely improve menopausal symptoms, including colpoxerosis. PMID- 26848803 TI - Project ECHO (Extension for Community Healthcare Outcomes): A new model for educating primary care providers about treatment of substance use disorders. AB - BACKGROUND: Project ECHO (Extension for Community Healthcare Outcomes) trains and mentors primary care providers (PCPs) in the care of patients with complex conditions. ECHO is a distance education model that connects specialists with numerous PCPs via simultaneous video link for the purpose of facilitating case based learning. This article describes a teleECHO clinic based at the University of New Mexico Health Sciences Center that is focused on treatment of substance use disorders (SUDs) and behavioral health disorders. METHODS: Since 2005, specialists in treatment of SUDs and behavioral health disorders at Project ECHO have offered a weekly 2-hour Integrated Addictions and Psychiatry (IAP) TeleECHO Clinic focused on supporting PCP evaluation and treatment of SUDs and behavioral health disorders. We tabulate the number of teleECHO clinic sessions, participants, and CME/CEU (continuing medical education/continuing education unit) credits provided annually. This teleECHO clinic has also been used to recruit physicians to participate in DATA-2000 buprenorphine waiver trainings. Using a database of the practice location of physicians who received the buprenorphine waiver since 2002, the number of waivered physicians per capita in US states was calculated. The increase in waivered physicians practicing in underserved areas in New Mexico was evaluated and compared with the rest of the United States. RESULTS: Since 2008, approximately 950 patient cases have been presented during the teleECHO clinic, and more than 9000 hours of CME/CEU have been awarded. Opioids are the substances discussed most commonly (31%), followed by alcohol (21%) and cannabis (12%). New Mexico is near the top among US states in DATA-2000 buprenorphine-waivered physicians per capita, and it has had much more rapid growth in waivered physicians practicing in traditionally underserved areas compared with the rest of the United States since the initiation of the teleECHO clinic focused on SUDs in 2005. CONCLUSION: The ECHO model provides an opportunity to promote expansion of access to treatment for opioid use disorder and other SUDs, particularly in underserved areas. PMID- 26848804 TI - Sclerosing Mesenteritis and Disturbance of Glucose Metabolism: A New Relationship? A Case Series. AB - BACKGROUND: Sclerosing mesenteritis is an idiopathic inflammatory and fibrotic disease that affects the mesentery. It is a rare disease, with the total number of reported cases in the literature ranging from 122 to 300. It mainly affects men in the sixth decade of life, and its etiology remains unknown. Clinical presentation is variable, but it is frequently asymptomatic. Diagnosis is often made by computed tomography (CT) scan, although biopsy may be needed for confirmation. An association between other diseases (e.g., neoplasms) and sclerosing mesenteritis has been described, but the relationship between the latter and glucose changes is not disclosed in the currently available literature. CASE REPORT: Five cases of sclerosing mesenteritis and glucose metabolism disorders (impaired fasting glucose and type 2 diabetes mellitus) were retrospectively collected and analyzed. The mean age was 65 +/- 9.3 years, 80% were male, and all patients were white. Three patients were asymptomatic and the other 2 (40%) had non-specific chronic abdominal pain. Blood tests revealed normal inflammatory parameters (mean HbA1c was 6.4% and fasting blood glucose was 140 mg/dL). The diagnosis was made by abdominal CT scan. The 2 symptomatic patients underwent therapy with colchicine 1 mg/day, with clinical improvement. During the mean 43-month follow-up period, there was no symptomatic progression, thereby maintaining the usual benign course of this condition. CONCLUSIONS: Sclerosing mesenteritis has only been described in small series and isolated cases, but its diagnosis is becoming more common due to greater access to diagnostic methods and higher awareness of the disease in the medical community. Furthermore, despite the small sample size, we describe a possible association between glucose metabolism impairment and sclerosing mesenteritis. PMID- 26848805 TI - CoSe2 and NiSe2 Nanocrystals as Superior Bifunctional Catalysts for Electrochemical and Photoelectrochemical Water Splitting. AB - Catalysts for oxygen evolution reactions (OER) and hydrogen evolution reactions (HER) are central to key renewable energy technologies, including fuel cells and water splitting. Despite tremendous effort, the development of low-cost electrode catalysts with high activity remains a great challenge. In this study, we report the synthesis of CoSe2 and NiSe2 nanocrystals (NCs) as excellent bifunctional catalysts for simultaneous generation of H2 and O2 in water-splitting reactions. NiSe2 NCs exhibit superior electrocatalytic efficiency in OER, with a Tafel slope (b) of 38 mV dec(-1) (in 1 M KOH), and HER, with b = 44 mV dec(-1) (in 0.5 M H2SO4). In comparison, CoSe2 NCs are less efficient for OER (b = 50 mV dec(-1)), but more efficient for HER (b = 40 mV dec(-1)). It was found that CoSe2 NCs contained more metallic metal ions than NiSe2, which could be responsible for their improved performance in HER. Robust evidence for surface oxidation suggests that the surface oxide layers are the actual active sites for OER, and that CoSe2 (or NiSe2) under the surface act as good conductive layers. The higher catalytic activity of NiSe2 is attributed to their oxide layers being more active than those of CoSe2. Furthermore, we fabricated a Si-based photoanode by depositing NiSe2 NCs onto an n-type Si nanowire array, which showed efficient photoelectrochemical water oxidation with a low onset potential (0.7 V versus reversible hydrogen electrode) and high durability. The remarkable catalytic activity, low cost, and scalability of NiSe2 make it a promising candidate for practical water-splitting solar cells. PMID- 26848806 TI - Depression Training in an Assisted Living Facility: A Pilot Study. AB - Depression in older adults residing in assisted living facilities (ALFs) is often not recognized. ALF staff who work with residents on a daily basis are the most likely individuals to recognize residents' depressive symptoms. The purpose of the current pilot study was to determine feasibility of a 4-week training program for 15 direct care staff to recognize any depression symptoms of 32 residents. Although training significantly improved knowledge, it did not improve staff recognition of residents with positive depressive symptoms. Staff reported the training provided them a better understanding about depression and rated the training as very helpful to be able to recognize depression symptoms. Staff requested more information on ways to respond to someone who is depressed. Additional training should emphasize staff-resident communication skills for staff. Challenges included resident attrition and dwindling staff participation. Strategies to address these challenges are presented. [Journal of Psychosocial Nursing and Mental Health Services, 54(5), 25-31.]. PMID- 26848807 TI - Transperitoneal versus retroperitoneal approach for elective open abdominal aortic aneurysm repair. AB - BACKGROUND: There has been extensive debate in the surgical literature regarding the optimum surgical access approach to the infrarenal abdominal aorta during an operation to repair an abdominal aortic aneurysm. The published trials comparing retroperitoneal (RP) and transperitoneal (TP) aortic surgery show conflicting results. OBJECTIVES: To assess the effectiveness and safety of the transperitoneal versus retroperitoneal approach for elective open abdominal aortic aneurysm repair on mortality, complications, hospital stay and blood loss. SEARCH METHODS: The Cochrane Vascular Trials Search Co-ordinator searched the Cochrane Vascular Specialised Register (last searched May 2015) and CENTRAL (2015, Issue 4) and trials databases (May 2015). The review authors searched the Chinese Biomedical Literature Database and other resources including clinical trials registers. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that assessed the TP approach versus the RP approach for elective open abdominal aortic aneurysm (AAA) repair. We evaluated the outcomes of mortality, complications, intensive care unit (ICU) stay, hospital stay, blood loss, aortic cross-clamp time and operating time. Two review authors independently selected RCTs against the inclusion criteria. We resolved any disagreements by discussion with a third review author. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from the included trials. We resolved any disagreements by discussion with a third review author. Two review authors independently assessed the risk of bias according to a standard quality checklist provided by Cochrane Vascular. MAIN RESULTS: We included four RCTs, with a combined total of 129 participants, that assessed the TP approach versus the RP approach for elective open AAA repair. The overall quality of the evidence was low to very low because of the low methodological quality of the included trials (unclear random sequence generation method and allocation concealment, and no blinding of outcome assessors), small sample sizes, small number of events, high heterogeneity and inconsistency between the included trials, no power calculations and relatively short follow-up. There were no differences between the RP approach and the TP approach regarding mortality (odds ratio (OR) 0.32, 95% CI 0.01 to 8.25; 110 participants; four trials; P = 0.49; I2 statistic = 0%; very low quality evidence). However, the RP approach may increase complications, such as hematoma (OR 0.90, 95% CI 0.13 to 6.48; 75 participants; two trials; P = 0.92; very low quality evidence), chronic wound pain (OR 2.20, 95% CI 0.36 to 13.34; 48 participants; one trial; P = 0.39; very low quality evidence) and abdominal wall hernia (OR 10.76, 95% CI 0.55 to 211.78; 48 participants; one trial; P = 0.12; very low quality evidence) compared with the TP approach in the patients for elective open AAA repair, but the confidence intervals (CIs) were wide. The RP approach reduced the blood loss (mean difference (MD) -504.87 mL, 95% CI -779.19 to -230.56; 129 participants; four trials; P = 0.003; very low quality evidence), ICU stay (MD -19.00 hours, 95% CI -31.41 to -6.59; 83 participants; two trials; P = 0.003; low quality evidence) and hospital stay (MD 3.14 days, 95% CI -4.82 to -1.45; 129 participants; four trials; P = 0.0003; low quality evidence). There were no differences between the RP approach and the TP approach regarding aortic cross-clamp time (MD 0.69 mins, 95% CI -7.23 to 8.60; 129 participants; four trials; P = 0.86; very low quality evidence) and operating time (MD -15.94 mins, 95% CI -34.76 to 2.88; 129 participants; four trials; P = 0.10; very low quality evidence). AUTHORS' CONCLUSIONS: Very low quality evidence from four small RCTs indicates that the RP approach did not have advantages over the TP approach for elective open AAA repair in terms of mortality. Moreover, the RP approach may increase the risk of postoperative wound complications although the CIs were wide.Low quality evidence shows that the RP approach could reduce blood loss, hospital stay and ICU stay compared with the TP approach. Very low quality evidence shows no differences between the RP approach and TP approaches in aortic cross-clamp time and operating time.Further large-scale RCTs of the RP approach versus TP approach for elective open AAA repair are required. PMID- 26848808 TI - Incidence and incidence trends of the most frequent cancers in adolescent and young adult Americans, including "nonmalignant/noninvasive" tumors. AB - BACKGROUND: Incidence rates and trends of cancers in adolescents and young adults (AYAs) ages 15 to 39 years were reexamined a decade after the US National Cancer Institute AYA Oncology Progress Review Group was established. METHODS: Data from the Surveillance, Epidemiology, and End Results program through 2011 were used to ascertain incidence trends since the year 2000 of the 40 most frequent cancers in AYAs, including tumors with nonmalignant/noninvasive behavior. RESULTS: Seven cancers in AYAs exhibited an overall increase in incidence; in 4, the annual percent change (APC) exceeded 3 (kidney, thyroid, uterus [corpus], and prostate cancer); whereas, in 3, the APC was between 0.7 and 1.4 (acute lymphoblastic leukemia and cancers of the colorectum and testis). Eight cancers exhibited statistically significant decreases in incidence among AYAs: Kaposi sarcoma (KS), fibromatous neoplasms, melanoma, and cancers of the anorectum, bladder, uterine cervix, esophagus, and lung, each with an APC less than -1. AYAs had a higher proportion of noninvasive tumors than either older or younger patients. CONCLUSIONS: An examination of cancer incidence patterns in AYAs observed over the recent decade reveal a complex pattern. Thyroid cancer by itself accounts for most of the overall increase and is likely caused by overdiagnosis. Reductions in cervix and lung cancer, melanoma, and KS can be attributed to successful national prevention programs. A higher proportion of noninvasive tumors in AYAs than in children and older adults indicates a need to revise the current system of classifying tumors in this population. PMID- 26848809 TI - Correction: Silver(i) complexes as precursors to produce silver nanowires: structure characterization, antimicrobial activity and cell viability. PMID- 26848810 TI - Numeric Estimates of Teratogenic Severity from Embryo-Fetal Developmental Toxicity Studies. AB - A developing organism exposed to a toxicant will have a response that ranges from none to severe (i.e., death or malformation). The response at a given dosage may be termed teratogenic (or developmental toxic) severity and is dependent on exposure conditions. Prenatal/embryo-fetal developmental (EFD) toxicity studies in rodents and rabbits are the most consistent and definitive assessments of teratogenic severity, and teratogenesis screening assays are best validated against their results. A formula is presented that estimates teratogenic severity for each group, including control, within an EFD study. The developmental components include embryonic/fetal death, malformations, variations, and mean fetal weight. The contribution of maternal toxicity is included with multiplication factors to adjust for the extent of mortality, maternal body weight change, and other parameters deemed important. The derivation of the formula to calculate teratogenic severity is described. Various EFD data sets from the literature are presented to highlight considerations to the calculation of the various components of the formula. Each score is compared to the concurrent control group to obtain a relative teratogenic severity. The limited studies presented suggest relative scores of two- to = fivefold higher than control have increasingly more severe teratogenicity. Such scores may help refine the concept of an exposure-based validation list for use by proponents of screening assays (Daston et al., 2014) by estimating the severity of "positive" exposures, or in other situations by defining the severity of a LOAEL (lowest observed adverse effect level). PMID- 26848812 TI - Comparison of Coronary Artery Disease Consortium 1 and 2 Scores and Duke Clinical Score to Predict Obstructive Coronary Disease by Invasive Coronary Angiography. AB - BACKGROUND: The first step in evaluating a patient with suspected stable coronary artery disease (CAD) is the determination of the pretest probability. The European Society of Cardiology guidelines recommend the use of the CAD Consortium 1 score (CAD1), which contrary to CAD Consortium 2 (CAD2) score and Duke Clinical Score (DCS), does not include modifiable cardiovascular risk factors. HYPOTHESIS: Using scores that include modifiable risk factors (DCS and CAD2) enhances prediction of CAD. METHODS: We retrospectively included all patients referred to invasive coronary angiography for suspected CAD from January/2008-December/2012 (N = 2234). Pretest probability was calculated using 3 models (CAD1, DCS, and CAD2), and they were compared using the net reclassification improvement. RESULTS: Mean patient age was 63.7 years, 67.5% were male, and the majority (66.9%) had typical angina. Coronary artery disease was diagnosed in 58.5%, and the area under the curve was 0.685 for DCS, 0.664 for CAD1, and 0.683 for CAD2, with a statistically significant difference between CAD1 and the others (P < 0.001). The net reclassification improvement was 20% for DCS, related to adequate reclassification of 32% of patients with CAD to a higher risk category, and 5% for CAD2, at the cost of adequate reclassification of 34% of patients without CAD to a lower risk category. CONCLUSIONS: Prediction of CAD using scores that include modifiable cardiovascular risk factors seems to improve accuracy. Our results suggest that, in high-prevalence populations, DCS may better identify patients at higher risk and CAD2 those at lower risk for CAD. PMID- 26848813 TI - Disentangling the associations between parental BMI and offspring body composition using the four-component model. AB - OBJECTIVES: This study sets out to investigate the intergenerational associations between the body mass index (BMI) of parents and the body composition of their offspring. METHODS: The cross-sectional data were analyzed for 511 parent offspring trios from London and south-east England. The offspring were aged 5-21 years. Parental BMI was obtained by recall and offspring fat mass and lean mass were obtained using the four-component model. Multivariable regression analysis, with multiple imputation for missing paternal values was used. Sensitivity analyses for levels of non-paternity were conducted. RESULTS: A positive association was seen between parental BMI and offspring BMI, fat mass index (FMI), and lean mass index (LMI). The mother's BMI was positively associated with the BMI, FMI, and LMI z-scores of both daughters and sons and of a similar magnitude for both sexes. The father's BMI showed similar associations to the mother's BMI, with his son's BMI, FMI, and LMI z-scores, but no association with his daughter. Sensitivity tests for non-paternity showed that maternal coefficients remained greater than paternal coefficients throughout but there was no statistical difference at greater levels of non-paternity. CONCLUSIONS: We found variable associations between parental BMI and offspring body composition. Associations were generally stronger for maternal than paternal BMI, and paternal associations appeared to differ between sons and daughters. In this cohort, the mother's BMI was statistically significantly associated with her child's body composition but the father's BMI was only associated with the body composition of his sons. Am. J. Hum. Biol. 28:524-533, 2016. (c) 2016 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc. PMID- 26848815 TI - Functionalization of Two-Dimensional Transition-Metal Dichalcogenides. AB - Two-dimensional (2D) layered transition-metal dichalcogenides (TMDs) are a fascinating class of nanomaterials that have the potential for application in catalysis, electronics, photonics, energy storage, and sensing. TMDs are rather inert, and thus pose problems for chemical derivatization. However, to further modify the properties of TMDs and fully harness their capabilities, routes towards their chemical functionalization must be identified. Herein, recent efforts toward the chemical (bond-forming) functionalization of 2D TMDs are critically reviewed. Recent successes are highlighted, along with areas where further detailed analyses and experimentation are required. This burgeoning field is very much in its infancy but has already provided several important breakthroughs. PMID- 26848814 TI - Vitamin D Status and Gestational Diabetes: Effect of Smoking Status during Pregnancy. AB - BACKGROUND: Vitamin D status, as measured by serum 25-hydroxyvitamin D (25(OH)D), has been shown in some studies to be inversely associated with gestational diabetes risk. Recently, it has been suggested that maternal smoking status may modify this relationship. We explored the association between 25(OH)D concentration and gestational diabetes and determined if there was an interaction between smoking and 25(OH)D. METHODS: A nested case-control study was conducted in Halifax, Nova Scotia and Quebec City, Quebec. Women were recruited before 20 weeks gestation and 25(OH)D was measured. Cases were women who developed gestational diabetes and controls were frequency matched to cases on study site, gestational age at blood draw, and season and year of blood draw. Logistic regression models estimated adjusted odds ratios (aOR) and 95% confidence intervals (CI). Models were tested for multiplicative and additive interaction, which was estimated by relative excess risk due to interaction (RERI). RESULTS: The study included 395 gestational diabetes cases and 1925 controls. Women who smoked during pregnancy and had 25(OH)D concentrations <30 nmol/L had an aOR = 3.73 [95% CI 1.95, 7.14] compared to non-smokers with 25(OH)D concentrations >=50 nmol/L. Additive interaction was detected between smoking status and 25(OH)D [RERI = 2.44, 95% CI 0.03, 4.85]. CONCLUSION: Our study supports the inverse association of vitamin D status with gestational diabetes risk, particularly among women who smoke during pregnancy. More research is needed to confirm this finding and, if confirmed, to determine the mechanism by which the combined effect of smoking and low vitamin D status increases the risk of developing gestational diabetes. PMID- 26848817 TI - Untangling the structure of the TDP-43 N-terminal domain. PMID- 26848816 TI - Effects of orally administered enalapril on blood pressure and hemodynamic response to vasopressors during isoflurane anesthesia in healthy dogs. AB - OBJECTIVE: To examine whether preanesthetic administration of enalapril, compared with placebo, results in a greater decline in blood pressure (BP) or decreased responsiveness of BP to isotonic fluids or vasopressors in healthy dogs during isoflurane anesthesia. STUDY DESIGN: Randomized, experimental, placebo controlled, blinded, crossover study. ANIMALS: Twelve healthy, female, purpose bred beagles. METHODS: Dogs underwent the following week-long treatment protocols, each preceded by a 1 week washout period: oral placebo twice daily (PLA); oral enalapril, 0.5 mg kg(-1) twice daily, with the 15th dose withheld on the day of anesthesia (ENA-W), and oral enalapril, 0.5 mg kg(-1) twice daily, with the 15th dose administered 90 minutes prior to anesthetic induction (ENA). On day 8 of each treatment period, dogs were anesthetized in random order utilizing a standard protocol. Following stabilization at an end-tidal isoflurane concentration (Fe'Iso) of 1.3%, invasively measured systolic (SAP), diastolic (DAP) and mean (MAP) arterial blood pressure were continuously recorded via telemetry. Hypotension (SAP < 85 mmHg) was treated with the following sequential interventions: lactated Ringer's solution (LRS) bolus (10 mL kg(-1) ); repeated LRS bolus; dopamine (7 MUg kg(-1) min(-1) ); and dopamine (10 MUg kg(-1) min( 1) ) first without and then with vasopressin (1 mU kg(-1) hour(-1) ). RESULTS: Compared with the PLA but not the ENA-W group, the ENA group had significantly lower average SAP, DAP and MAP at an Fe'Iso of 1.3%, spent more minutes in hypotension, and required a greater number of interventions to correct moderate to-severe mean arterial hypotension. CONCLUSIONS: In healthy dogs, enalapril administered 90 minutes prior to isoflurane anesthesia increases the degree of intra-anesthetic hypotension and the number of interventions required to correct moderate-to-severe hypotension. CLINICAL RELEVANCE: Dogs receiving angiotensin converting enzyme inhibitors on the day of anesthesia may exhibit clinically significant intra-anesthetic hypotension. PMID- 26848818 TI - Efficient sequence-specific isolation of DNA fragments and chromatin by in vitro enChIP technology using recombinant CRISPR ribonucleoproteins. AB - The clustered regularly interspaced short palindromic repeats (CRISPR) system is widely used for various biological applications, including genome editing. We developed engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR to isolate target genomic regions from cells for their biochemical characterization. In this study, we developed 'in vitro enChIP' using recombinant CRISPR ribonucleoproteins (RNPs) to isolate target genomic regions. in vitro enChIP has the great advantage over conventional enChIP of not requiring expression of CRISPR complexes in cells. We first showed that in vitro enChIP using recombinant CRISPR RNPs can be used to isolate target DNA from mixtures of purified DNA in a sequence-specific manner. In addition, we showed that this technology can be used to efficiently isolate target genomic regions, while retaining their intracellular molecular interactions, with negligible contamination from irrelevant genomic regions. Thus, in vitro enChIP technology is of potential use for sequence-specific isolation of DNA, as well as for identification of molecules interacting with genomic regions of interest in vivo in combination with downstream analysis. PMID- 26848819 TI - Novel application of high-dose rate brachytherapy for severe, recalcitrant palmoplantar pustulosis. AB - Palmoplantar pustulosis (PPP) is a chronic pustular dermatitis of the palms and soles, which is frequently associated with significant pruritus and pain, often limiting daily activities. We present the case of a 36-year-old man with severe PPP who had treatment failure with multiple medical therapies but showed marked improvement with high-dose rate brachytherapy. Brachytherapy has the advantage of providing a conformal dose distribution over complex curved surfaces, such as the foot and ankle. Our observations suggest that brachytherapy may be a well tolerated treatment option for patients with severe, refractory PPP. PMID- 26848820 TI - Cantilever Lengths and Anterior-Posterior Spreads of Interim, Acrylic Resin, Full Arch Screw-Retained Prostheses and Their Relationship to Prosthetic Complications. AB - PURPOSE: To retrospectively record the distal cantilever lengths (CL) of full arch interim, all-acrylic resin prostheses used in an immediate occlusal loading protocol. Anterior/posterior (A/P) spreads were measured on master casts associated with the interim prostheses. Ratios were calculated (CL/AP). Prosthetic complications were recorded. The ratios and prosthetic complications were statistically compared and analyzed for statistical and clinical significance. MATERIALS AND METHODS: One hundred twenty-eight patients with 192 edentulous arches (109 maxillary; 83 mandibular; 190 arches were restored with 4 implants; 2 maxillary arches were restored with 5 implants) were treated. Seven hundred seventy implants (Branemark System) from September 1, 2011, until August 31, 2013 were included in this report. Patients were treated and followed in a single private practice for up to 40 months. Implants had to have at least 35 Ncm of insertion torque to be immediately loaded. All implants were immediately loaded with full functional occlusions on the day the implants were placed. Interim, full-arch, all-acrylic resin prostheses were fabricated and placed into full functional occlusion following an All-on-Four protocol. Measurements of the distal cantilevered segments were made on the prostheses prior to insertion. A/P spreads were measured on the master casts made from abutment level impressions made on the day of surgery. Prosthetic complications (denture base fracture, cohesive/adhesive denture tooth fractures) were recorded in the charts as they occurred. All charts were reviewed for this report; no patients were lost to follow-up. Interim prosthetic repairs were analyzed by type (tooth or denture base), arch, gender, and location within the edentulous arches. RESULTS: One patient experienced complete maxillary implant failure; the overall implant survival rate (SR) was 99.5% (766 of 770). Four hundred thirty of 434 maxillary implants and 336 of 336 mandibular implants survived for SRs of 99.1 and 100%, respectively. Thirty four of the 192 interim prostheses (17.7%) warranted at least one repair during treatment. The average cantilevered segments for the interim maxillary prostheses without prosthetic complications were 9.7 mm (right) and 9.5 mm (left). The average cantilevered segments for the repaired maxillary prostheses were 10.1 mm (right); 9.9 mm (left). The average cantilevered segments for the interim mandibular prostheses without prosthetic complications were 9.2 mm (right) and 9.3 mm (left). The average cantilevered segments for the repaired mandibular prostheses were 9.87 mm (right) and 9.18 mm (left). The average maxillary A/P spread was 18.4 mm; the average mandibular A/P spread was 17.3 mm. The average maxillary CL/AP spread ratios were 0.55 (right) and 0.53 (left); the average mandibular CL/AP spread ratios were 0.61 (right) and 0.57 (left). There were no statistical correlations between the CL/AP ratios and the frequency or type of prosthetic repairs recorded in this study. The ratios were statistically significant (p = 0.041) for mandibular prostheses with prosthetic complications: slightly greater CL/A-P ratios were noted. CONCLUSIONS: The results from this 2 year clinical retrospective analysis indicated that CL/AP ratios in the range of 0.5 to 0.6 generally resulted in successful interim prostheses during the time the interim prostheses were in function. The results of this investigation also revealed that 1 of 129 patients experienced implant failures; implants placed and restored on the same day with full-arch, screw-retained prostheses resulted in high clinical survival rates for implants and prostheses. The All-on-Four treatment protocol used in this study was a viable alternative to other implant loading/placement protocols for rehabilitating edentulous patients and resulted in minimal prosthetic complications. PMID- 26848821 TI - An integrated practical implementation of continuous aqueous two-phase systems for the recovery of human IgG: From the microdevice to a multistage bench-scale mixer-settler device. AB - Aqueous two-phase systems (ATPS) are a liquid-liquid extraction technology with clear process benefits; however, its lack of industrial embracement is still a challenge to overcome. Antibodies are a potential product to be recovered by ATPS in a commercial context. The objective of this work is to present a more integral approach of the different isolated strategies that have arisen in order to enable a practical, generic implementation of ATPS, using human immunoglobulin G (IgG) as experimental model. A microfluidic device is used for ATPS parameters preselection for product recovery. ATPS were continuously operated in a mixer settler device in one stage, multistage and multistage with recirculation configuration. Single-stage pure IgG extraction with a polyethylene glycol (PEG) 3350-phophates ATPS within continuous operation allowed a 65% recovery. Further implementation of a multistage platform promoted a higher particle partitioning reaching a 90% recovery. The processing of IgG from a cell supernatant culture harvest in a multistage system with top phase recirculation resulted in 78% IgG recovery in bottom phase. This work conjugates three not widely spread methodologies for ATPS: microfluidics, continuous and multistage operation. PMID- 26848824 TI - Simultaneous degradation of ofloxacin and recovery of Cu(II) by photoelectrocatalysis with highly ordered TiO2 nanotubes. AB - A photoelectrocatalytic system for removal of ofloxacin and Cu(2+) complex was developed. In such a photoelectrocatalytic system, highly ordered titanium dioxide nanotubes served as a highly active photoanode for photoelectrocatalytic degradation of ofloxacin; and titanium plate was used as the cathode, on which Cu(2+) ions were electrodeposited. Compared with other treatment methods including photocatalysis, electrochemistry and direct photolysis, photoelectrocatalytic technique exhibited the highest removal efficiency for either ofloxacin or Cu(2+). To obtain the optimum photoelectrocatalytic operation conditions, some influencing factors such as current, pH and supporting electrolyte concentration were investigated systematically. The mutual influence analysis indicated that the photoelectrocatalytic removal efficiency of ofloxacin was first promoted by Cu(2+) but was then suppressed with prolonging the treatment time; whereas the removal of Cu(2+) was always promoted by ofloxacin over the whole photoelectrocatalytic treatment process. Furthermore, the photoelectrocatalytic removal of ofloxacin -Cu(2+) was studied by differential pulse voltammetry and high-performance liquid chromatography-mass spectrometry. The results indicated that although Cu(2+) influenced the removal rate of ofloxacin, it did not change the degradation mechanism of ofloxacin. The formation of an electroactive intermediate product during the photoelectrocatalytic process was clearly observed by voltammetric analysis. Based on intermediate products identified by high-performance liquid chromatography-mass spectrometry, a possible photoelectrocatalytic removal mechanism for ofloxacin -Cu(2+) was proposed. PMID- 26848825 TI - Pretreatment of ultra-high concentrated wastewater from phthalonitrile resin manufacturing by chemical precipitation, reduction and oxidation. AB - To remove the toxic and refractory pollutants in the phthalonitrile resin wastewater and improve its biodegradability, a combined process (i.e., CaCl2+AA+Fe/Cu/air) was developed to pretreat this wastewater obtained from a phthalonitrile resin manufacturing plant in southwestern China. First, CO3(2-) was precipitated and removed by adding CaCl2. Furthermore, its ultra-high concentrated NO2(-) (22.7+/-0.1 g/L) was reduced into N2 by adding amidosulphonic acid (AA). Meanwhile, two control experiments were setup to confirm the superiority of the combined process (i.e., CaCl2+AA). Subsequently, the wastewater was further treated by Fe/Cu/air process after the removal of CO3(2-) and NO2(-). The results suggest that the developed method not only could effectively remove the ultra-high concentrated CO3(2-) (>99%) and NO2(-) (>99%), but also could obtain high COD (58.8%) and colority (95.2%) removal efficiencies. Meanwhile, B/C ratio of this wastewater increased from 0.19 to 0.45, which suggests the biodegradability also was improved significantly. Finally, the high treatment efficiency was mainly attributed to the synergistic effects of CaCl2, AA and Fe/Cu/air. Therefore, the combined process is a promising pretreatment process for the ultra-high concentrated wastewater from phthalonitrile resin manufacturing. PMID- 26848826 TI - Investigation of the Interactions and Bonding between Carbon and Group VIII Metals at the Atomic Scale. AB - The nature and dynamics of bonding between Fe, Ru, Os, and single-walled carbon nanotubes (SWNTs) is studied by aberration-corrected high-resolution transmission electron microscopy (AC-HRTEM). The metals catalyze a wide variety of different transformations ranging from ejection of carbon atoms from the nanotube sidewall to the formation of hollow carbon shells or metal carbide within the SWNT, depending on the nature of the metal. The electron beam of AC-HRTEM serves the dual purpose of providing energy to the specimen and simultaneously enabling imaging of chemical transformations. Careful control of the electron beam parameters, energy, flux, and dose allowed direct comparison between the metals, demonstrating that their chemical reactions with SWNTs are determined by a balance between the cohesive energy of the metal particles and the strength of the metal-carbon sigma- or pi-bonds. The pathways of transformations of a given metal can be drastically changed by applying different electron energies (80, 40, or 20 keV), thus demonstrating AC-HRTEM as a new tool to direct and study chemical reactions. The understanding of interactions and bonding between SWNT and metals revealed by AC-HRTEM at the atomic level has important implications for nanotube-based electronic devices and catalysis. PMID- 26848822 TI - Transfusion of recently donated (fresh) red blood cells (RBCs) does not improve survival in comparison with current practice, while safety of the oldest stored units is yet to be established: a meta-analysis. AB - BACKGROUND AND OBJECTIVES: Preclinical studies generated the hypothesis that older stored red blood cells (RBCs) can increase transfusion risks. To examine the most updated and complete clinical evidence and compare results between two trial designs, we assessed both observational studies and randomized controlled trials (RCTs) studying the effect of RBC storage age on mortality. MATERIALS AND METHODS: Five databases were searched through December 2014 for studies comparing mortality using transfused RBCs having longer and shorter storage times. RESULTS: Analysis of six RCTs found no significant differences in survival comparing current practice (average storage age of 2 to 3 weeks) to transfusion of 1- to 10 day-old RBCs (OR 0.91, 95% CI 0.77-1.07). RBC storage age was lower in RCTs vs. observational studies (P = 0.01). The 31 observational studies found an increased risk of death (OR 1.13, 95% CI 1.03-1.24) (P = 0.01) with increasing age of RBCs, a different mortality effect than RCTs (P = 0.02). CONCLUSION: RCTs established that transfusion of 1- to 10-day-old stored RBCs is not superior to current practice. The apparent discrepancy in mortality between analyses of RCTs and observational studies may in part relate to differences in hypotheses tested and ages of stored RBCs studied. Further trials investigating 1- to 10-day-old stored RBC benefits would seem of lower priority than studies to determine whether 4- to 6-week stored units have safety and efficacy equivalent to the 2- to 3-week-old stored RBCs commonly transfused today. PMID- 26848827 TI - Sculpting the internal architecture of fluorescent silica particles via a template-free approach. AB - Particles with an open, porous structure can be used to deliver payloads. It is often of interest to detect such particles in tissue or materials, which is facilitated by addition of dye. A straightforward approach leading to fluorescent, porous silica particles is described. The particles are etched with 3mM aqueous sodium hydroxide, taking advantage of the etching rate difference between normal silica and an interior band of silica that contains covalently attached dye. No additional steps, such as dye labeling or thermal annealing, are required. Etching modeled the internal structure of the fluorescent silica particles by creating meso/macropores and voids, as reflected by nitrogen absorption measurements. In order to investigate whether a polymer shell influences etching, certain composite particles are top-coated with poly(l lysine) representing neutral or positive charged surfaces under typical pH conditions in living systems. The polypeptide-coated fluorescent silica cores exhibit the same porous morphology as uncoated homologs. The polypeptide topcoat does little to alter the permeation by the etching agent. Preservation of size during etching, confirmed by dynamic light scattering, transmission electron microscopy and small-angle X-ray scattering, simplifies the use of these template free porous fluorescent particles as platforms for drug encapsulation, drug carriers and in vivo imaging. PMID- 26848829 TI - Laminin receptor is an interacting partner for viral outer capsid protein VP5 in grass carp reovirus infection. AB - Grass carp reovirus (GCRV) is responsible for viral hemorrhagic disease in cultured grass carp Ctenopharyngon idellus. Through yeast two-hybrid screen, laminin receptor (LamR) was identified as a potential interacting partner for the outer capsid protein VP5 of GCRV. We cloned and sequenced the gene encoding grass carp LamR. Viral attachment assay demonstrated the involvement of membrane associated LamR in GCRV infection. Solid-phase overlay assays demonstrated that GCRV interacted with GST-tagged LamR in vitro. In contrast to VP7, GST-tagged VP5 was shown to associate with LamR in both pull-down and solid-phase blot overlay assays. With the reduction of LamR expression in CIK cells achieved by RNAi, remarkably reduced infection efficiency of GCRV was observed. CIK cells pretreated with polyclonal antibody against LamR resulted in dose-dependent inhibition of GCRV infection. These results collectively indicated that grass carp LamR was involved in GCRV infection by interacting with viral outer capsid protein VP5. PMID- 26848831 TI - Thermodynamic Properties of Selected Homologous Series of Ionic Liquids Calculated Using Molecular Dynamics. AB - This work presents a molecular dynamics simulation study concerning the thermodynamic data of ionic liquids (ILs) including phase change enthalpies, liquid phase densities, radial and spatial distribution functions, and diffusive properties. Three homologous series of ILs were selected for this study, namely, 1-alkyl-3-methylimidazolium tetrafluoroborates, hexafluorophosphates, and 1,1,2,2 tetrafluoroethanesulfonates, so that properties of 36 ILs are calculated in total. The trends of calculated properties are compared to available experimental data and thoroughly discussed in context of the homologous series. The calculated trends of the vaporization enthalpies within the series are supported by analyzing the structural properties of the ILs. An excellent agreement of calculated structural properties (liquid phase density) with the experimental counterparts is reached. The calculated enthalpic properties are overestimated considerably; thus, further development of the force fields for ILs is required. PMID- 26848828 TI - Layer specific and general requirements for ERK/MAPK signaling in the developing neocortex. AB - Aberrant signaling through the Raf/MEK/ERK (ERK/MAPK) pathway causes pathology in a family of neurodevelopmental disorders known as 'RASopathies' and is implicated in autism pathogenesis. Here, we have determined the functions of ERK/MAPK signaling in developing neocortical excitatory neurons. Our data reveal a critical requirement for ERK/MAPK signaling in the morphological development and survival of large Ctip2(+) neurons in layer 5. Loss of Map2k1/2 (Mek1/2) led to deficits in corticospinal tract formation and subsequent corticospinal neuron apoptosis. ERK/MAPK hyperactivation also led to reduced corticospinal axon elongation, but was associated with enhanced arborization. ERK/MAPK signaling was dispensable for axonal outgrowth of layer 2/3 callosal neurons. However, Map2k1/2 deletion led to reduced expression of Arc and enhanced intrinsic excitability in both layers 2/3 and 5, in addition to imbalanced synaptic excitation and inhibition. These data demonstrate selective requirements for ERK/MAPK signaling in layer 5 circuit development and general effects on cortical pyramidal neuron excitability. PMID- 26848830 TI - Circovirus in domestic and wild carnivores: An important opportunistic agent? AB - Circoviruses are relatively novel pathogens with increased importance in canids. In this study, we first screened the presence of dog circovirus (DogCV) by molecular methods from a total number of 389 internal organ samples originating from 277 individuals of domestic dogs and wild animals including wolves, foxes and badgers. All the animals originated from Central-Southern Italy, specifically from Abruzzi and Molise regions, areas hosting several natural parks. DogCV was detected in 9/34 wolves (P=26.4%; IC 95%: 14.6-43.1%), 8/209 dogs (P=3.8%; IC 95%: 1.9-7.3%), 0/24 foxes (P=0%; IC 95%: 0-13.8%), 1/10 badgers (P=10%; IC 95%: 1.79-40.4%). However, all DogCV positive animals were shown to be infected at least by an additional key pathogen, including canine distemper virus (CDV) and canine parvovirus type 2. All wolves, but one, presenting DogCV in the internal tissues suffered from CDV infection. The DNA purified from 17 DogCV infected organs was used for whole genome sequencing and phylogenetic analysis. PMID- 26848832 TI - Electrooxidation of Ethanol and Methanol Using the Molecular Catalyst [{Ru4O4(OH)2(H2O)4}(gamma-SiW10O36)2](10.). AB - Highly efficient electrocatalytic oxidation of ethanol and methanol has been achieved using the ruthenium-containing polyoxometalate molecular catalyst, [{Ru4O4(OH)2(H2O)4}(gamma-SiW10O36)2](10-) ([1(gamma-SiW10O36)2](10-)). Voltammetric studies with dissolved and surface-confined forms of [1(gamma SiW10O36)2](10-) suggest that the oxidized forms of 1 can act as active catalysts for alcohol oxidation in both aqueous (over a wide pH range covering acidic, neutral, and alkaline) and alcohol media. Under these conditions, the initial form of 1 also exhibits considerable reactivity, especially in neutral solution containing 1.0 M NaNO3. To identify the oxidation products, preparative scale bulk electrolysis experiments were undertaken. The products detected by NMR, gas chromatography (GC), and GC-mass spectrometry from oxidation of ethanol are 1,1 diethoxyethane and ethyl acetate formed from condensation of acetaldehyde or acetic acid with excess ethanol. Similarly, the oxidation of methanol generates formaldehyde and formic acid which then condense with methanol to form dimethoxymethane and methyl formate, respectively. These results demonstrate that electrocatalytic oxidation of ethanol and methanol occurs via two- and four electron oxidation processes to yield aldehydes and acids. The total faradaic efficiencies of electrocatalytic oxidation of both alcohols exceed 94%. The numbers of aldehyde and acid products per catalyst were also calculated and compared with the literature reported values. The results suggest that 1 is one of the most active molecular electrocatalysts for methanol and ethanol oxidation. PMID- 26848834 TI - Polyphenolic-polysaccharide conjugates from plants of Rosaceae/Asteraceae family as potential radioprotectors. AB - Polyphenolic-polysaccharide macromolecular, water-soluble glycoconjugates, isolated from the selected medicinal plants of Rosaceae/Asteraceae family: from leaves of Fragaria vesca L., Rubus plicatus Whe. et N. E., and from flowering parts of Sanguisorba officinalis L., and Erigeron canadensis L., were investigated for their ability to protect proteins and lipids of human plasma against gamma-radiation-induced oxidative damage. Treatment of plasma with plant conjugates (6, 30, 150 MUg/ml) prior exposure to 100 Gy radiation resulted in a significant inhibition of lipid peroxidation, evaluated by TBARS levels; conjugates isolated from E. canadensis and R. plicatus and a reference flavonoid quercetin showed similar high potential (approx. 70% inhibition, at 6 MUg/ml). The conjugates prevented radiation-induced oxidation of protein thiols and significantly improved plasma total antioxidant capacity, estimated with Ellman's reagent and ABTS(.+) assay, respectively. The results demonstrate by the first time a significant radioprotective capability of the polyphenolic-polysaccharide conjugates isolated from E. canadensis, R. plicatus, S. officinalis and to the less extent from F. vesca. The abilities of these substances to inhibit radiation induced lipid peroxidation and thiol oxidation in plasma seems to be mediated, but not limited to ROS scavenging activity. PMID- 26848833 TI - The Use of Innovative Two-Component Cluster Analysis and Serodiagnostic Cut-Off Methods to Estimate Prevalence of Pertussis Reinfections. AB - Bordetella pertussis circulates even in highly vaccinated countries affecting all age groups. Insight into the scale of concealed reinfections is important as they may contribute to transmission. We therefore investigated whether current single point serodiagnostic methods are suitable to estimate the prevalence of pertussis reinfection. Two methods based on IgG-Ptx plasma levels alone were used to evaluate the proportion of renewed seroconversions in the past year in a cohort of retrospective pertussis cases >= 24 months after a proven earlier symptomatic infection. A Dutch population database was used as a baseline. Applying a classical 62.5 IU/ml IgG-Ptx cut-off, we calculated a seroprevalence of 15% in retrospective cases, higher than the 10% observed in the population baseline. However, this method could not discriminate between renewed seroconversion and waning of previously infection-enhanced IgG-Ptx levels. Two-component cluster analysis of the IgG-Ptx datasets of both pertussis cases and the general population revealed a continuum of intermediate IgG-Ptx levels, preventing the establishment of a positive population and the comparison of prevalence by this alternative method. Next, we investigated the complementary serodiagnostic value of IgA-Ptx levels. When modelling datasets including both convalescent and retrospective cases we obtained new cut-offs for both IgG-Ptx and IgA-Ptx that were optimized to evaluate renewed seroconversions in the ex-cases target population. Combining these cut-offs two-dimensionally, we calculated 8.0% reinfections in retrospective cases, being below the baseline seroprevalence. Our study for the first time revealed the shortcomings of using only IgG-Ptx data in conventional serodiagnostic methods to determine pertussis reinfections. Improved results can be obtained with two-dimensional serodiagnostic profiling. The proportion of reinfections thus established suggests a relatively increased period of protection to renewed infection after clinical pertussis. PMID- 26848835 TI - Circular RNAs Co-Precipitate with Extracellular Vesicles: A Possible Mechanism for circRNA Clearance. AB - Backspliced circular RNAs (circRNAs) are prevalent in many eukaryotic systems and are spliced from thousands of different genes. Where examined, circRNAs are often highly stable and the mechanisms by which cells degrade and/or clear circRNAs from the cells are unknown. Here we investigated the possibility that cells can eliminate circRNAs into extracellular space, possibly within released vesicles such as exosomes and microvesicles. From three different cell lines and examining multiple circRNAs, we show that extracellular vesicle (EVs) preparations recovered from cell culture conditioned media contain established circRNAs. Moreover, these circRNAs are enriched over their linear counterparts within EV preparations when compared to the producing cells. This supports the idea that expulsion from cells into extracellular space, as by EVs release, can be a mechanism by which cells clear circRNAs. Moreover, since EVs can be taken up by other cells, excreted circRNAs could contribute to cell to cell communication. PMID- 26848836 TI - Functional Resilience against Climate-Driven Extinctions - Comparing the Functional Diversity of European and North American Tree Floras. AB - Future global change scenarios predict a dramatic loss of biodiversity for many regions in the world, potentially reducing the resistance and resilience of ecosystem functions. Once before, during Plio-Pleistocene glaciations, harsher climatic conditions in Europe as compared to North America led to a more depauperate tree flora. Here we hypothesize that this climate driven species loss has also reduced functional diversity in Europe as compared to North America. We used variation in 26 traits for 154 North American and 66 European tree species and grid-based co-occurrences derived from distribution maps to compare functional diversity patterns of the two continents. First, we identified similar regions with respect to contemporary climate in the temperate zone of North America and Europe. Second, we compared the functional diversity of both continents and for the climatically similar sub-regions using the functional dispersion-index (FDis) and the functional richness index (FRic). Third, we accounted in these comparisons for grid-scale differences in species richness, and, fourth, investigated the associated trait spaces using dimensionality reduction. For gymnosperms we find similar functional diversity on both continents, whereas for angiosperms functional diversity is significantly greater in Europe than in North America. These results are consistent across different scales, for climatically similar regions and considering species richness patterns. We decomposed these differences in trait space occupation into differences in functional diversity vs. differences in functional identity. We show that climate-driven species loss on a continental scale might be decoupled from or at least not linearly related to changes in functional diversity. This might be important when analyzing the effects of climate-driven biodiversity change on ecosystem functioning. PMID- 26848837 TI - Intra-Species Diversity and Panmictic Structure of Cryptosporidium parvum Populations in Cattle Farms in Northern Spain. AB - The intra-herd and intra-host genetic variability of 123 Cryptosporidium parvum isolates was investigated using a multilocus fragment typing approach with eleven variable-number tandem-repeat (VNTR) loci and the GP60 gene. Isolates were collected from intensively farmed diarrheic pre-weaned calves originating from 31 dairy farms in three adjoining regions in northern Spain (Pais Vasco, Cantabria and Asturias). The multilocus tool demonstrated an acceptable typeability, with 104/123 samples amplifying at all twelve loci. The ML2, TP14, GP60 and the previously un-described minisatellite at locus cgd2_3850 were the most discriminatory markers, while others may be dismissed as monomorphic (MSB) or less informative (CP47, ML1 and the novel minisatellites at loci Cgd1_3670 and Cgd6_3940). The 12-satellite typing tool provided a Hunter-Gaston index (HGDI) of 0.987 (95% CI, 0.982-0.992), and differentiated a total of 70 multilocus subtypes (MLTs). The inclusion of only the four most discriminatory markers dramatically reduced the number of MLTs (n: 44) but hardly reduced the HGDI value. A total of 54 MLTs were distinctive for individual farms, indicating that cryptosporidiosis is an endemic condition on most cattle farms. However, a high rate of mixed infections was detected, suggesting frequent meiotic recombination. Namely, multiple MLTs were seen in most farms where several specimens were analyzed (90.5%), with up to 9 MLTs being found on one farm, and individual specimens with mixed populations being reported on 11/29 farms. Bayesian Structure analysis showed that over 35% of isolates had mixed ancestry and analysis of evolutionary descent using the eBURST algorithm detected a high rate (21.4%) of MLTs appearing as singletons, indicating a high degree of genetic divergence. Linkage analysis found evidence of linkage equilibrium and an overall panmictic structure within the C. parvum population in this discrete geographical area. PMID- 26848838 TI - Raman Imaging Spectroscopy of a Putative Microfossil from the ~3.46 Ga Apex Chert: Insights from Quartz Grain Orientation. AB - The utility of nondestructive laser Raman for testing the biogenicity of microfossil-like structures in ancient rocks is promising, yet results from deposits like the ~3.46 Ga Apex chert remain contentious. The essence of the debate is that associated microstructures, which are not purported to be microfossils, also contain reduced carbon that displays Raman D- and G-band peaks similar to those seen in the purported microfossils. This has led to the hypothesis that all features including reported microfossils are due to compression of nonfossil carbon during crystal growth around quartz spherulites or more angular crystals. In this scenario, the precursor to this macromolecular carbon may or may not have been of biogenic origin, while the arcuate and linear features described would be pseudofossils. To test this hypothesis, we have undertaken 2-D micro-Raman imaging of the Eoleptonema apex holotype and associated features using instrumentation with a high spatial and spectral resolution. In addition to this, we utilized the ratio of two Raman active quartz mode intensities (I129/I461) to assess quartz grain orientation and grain splitting artifacts. These data lead us to conclude that the holotype of Eoleptonema apex is a sheet-shaped pseudofossil that appears to be a carbon infilled intragranular crack; therefore other holotypes should be carefully reexamined for syngenicity. PMID- 26848839 TI - GAD2 Alternative Transcripts in the Human Prefrontal Cortex, and in Schizophrenia and Affective Disorders. AB - Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC). No consistent changes in GAD2 expression have been found in brains from patients with schizophrenia. In this work, with the use of RNA sequencing and PCR technologies, we confirmed and tracked the expression of an alternative truncated transcript of GAD2 (ENST00000428517) in human control DLPFC homogenates across lifespan besides the well-known full length transcript of GAD2. In addition, using quantitative RT-PCR, expression of GAD2 full length and truncated transcripts were measured in the DLPFC of patients with schizophrenia, bipolar disorder and major depression. The expression of GAD2 full length transcript is decreased in the DLPFC of schizophrenia and bipolar disorder patients, while GAD2 truncated transcript is increased in bipolar disorder patients but decreased in schizophrenia patients. Moreover, the patients with schizophrenia with completed suicide or positive nicotine exposure showed significantly higher expression of GAD2 full length transcript. Alternative transcripts of GAD2 may be important in the growth and development of GABA synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders. PMID- 26848840 TI - Quantitative Evaluation of Performance in Interventional Neuroradiology: An Integrated Curriculum Featuring Theoretical and Practical Challenges. AB - PURPOSE: We sought to develop a standardized curriculum capable of assessing key competencies in Interventional Neuroradiology by the use of models and simulators in an objective, quantitative, and efficient way. In this evaluation we analyzed the associations between the practical experience, theoretical knowledge, and the skills lab performance of interventionalists. MATERIALS AND METHODS: We evaluated the endovascular skills of 26 participants of the Advanced Course in Endovascular Interventional Neuroradiology of the European Society of Neuroradiology with a set of three tasks (aneurysm coiling and thrombectomy in a virtual simulator and placement of an intra-aneurysmal flow disruptor in a flow model). Practical experience was assessed by a survey. Participants completed a written and oral examination to evaluate theoretical knowledge. Bivariate and multivariate analyses were performed. RESULTS: In multivariate analysis knowledge of materials and techniques in Interventional Neuroradiology was moderately associated with skills in aneurysm coiling and thrombectomy. Experience in mechanical thrombectomy was moderately associated with thrombectomy skills, while age was negatively associated with thrombectomy skills. We found no significant association between age, sex, or work experience and skills in aneurysm coiling. CONCLUSION: Our study gives an example of how an integrated curriculum for reasonable and cost-effective assessment of key competences of an interventional neuroradiologist could look. In addition to traditional assessment of theoretical knowledge practical skills are measured by the use of endovascular simulators yielding objective, quantitative, and constructive data for the evaluation of the current performance status of participants as well as the evolution of their technical competency over time. PMID- 26848842 TI - Correction: Effect of Pore Size and Porosity on the Biomechanical Properties and Cytocompatibility of Porous NiTi Alloys. PMID- 26848841 TI - Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru. AB - BACKGROUND: Nearly half of the world's population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010-2011, 15 years after the first outbreak of DENV-2 in the region. METHODOLOGY/PRINCIPAL FINDINGS: We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010 2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%-65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1-17.7). CONCLUSIONS/SIGNIFICANCE: Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics. PMID- 26848843 TI - Transcriptome Analysis of Flower Sex Differentiation in Jatropha curcas L. Using RNA Sequencing. AB - BACKGROUND: Jatropha curcas is thought to be a promising biofuel material, but its yield is restricted by a low ratio of instaminate/staminate flowers (1/10 1/30). Furthermore, valuable information about flower sex differentiation in this plant is scarce. To explore the mechanism of this process in J. curcas, transcriptome profiling of flower development was carried out, and certain genes related with sex differentiation were obtained through digital gene expression analysis of flower buds from different phases of floral development. RESULTS: After Illumina sequencing and clustering, 57,962 unigenes were identified. A total of 47,423 unigenes were annotated, with 85 being related to carpel and stamen differentiation, 126 involved in carpel and stamen development, and 592 functioning in the later development stage for the maturation of staminate or instaminate flowers. Annotation of these genes provided comprehensive information regarding the sex differentiation of flowers, including the signaling system, hormone biosynthesis and regulation, transcription regulation and ubiquitin mediated proteolysis. A further expression pattern analysis of 15 sex-related genes using quantitative real-time PCR revealed that gibberellin-regulated protein 4-like protein and AMP-activated protein kinase are associated with stamen differentiation, whereas auxin response factor 6-like protein, AGAMOUS like 20 protein, CLAVATA1, RING-H2 finger protein ATL3J, auxin-induced protein 22D, and r2r3-myb transcription factor contribute to embryo sac development in the instaminate flower. Cytokinin oxidase, Unigene28, auxin repressed-like protein ARP1, gibberellin receptor protein GID1 and auxin-induced protein X10A are involved in both stages mentioned above. In addition to its function in the differentiation and development of the stamens, the gibberellin signaling pathway also functions in embryo sac development for the instaminate flower. The auxin signaling pathway also participates in both stamen development and embryo sac development. CONCLUSIONS: Our transcriptome data provide a comprehensive gene expression profile for flower sex differentiation in Jatropha curcas, as well as new clues and information for further study in this field. PMID- 26848844 TI - Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus. AB - Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied, the changes in mechanical properties were modest. Moreover, the effect of ventricular enlargement is not limited to the CC+PVWM and ventral internal capsule, the extent of microstructural changes vary between brain regions, and there is regional and temporal variation in brain tissue stiffness during hydrocephalus development. PMID- 26848845 TI - Immunomodulatory and Anti-Inflammatory Activities of Chicken Cathelicidin-2 Derived Peptides. AB - Host Defence Peptides and derived peptides are promising classes of antimicrobial and immunomodulatory lead compounds. For this purpose we examined whether chicken cathelicidin-2 (CATH-2)-derived peptides modulate the function and inflammatory response of avian immune cells. Using a chicken macrophage cell line (HD11) we found that full-length CATH-2 dose-dependently induced transcription of chemokines CXCLi2/IL-8, MCP-3 and CCLi4/RANTES, but not of pro-inflammatory cytokine IL-1beta. In addition, CATH-2 efficiently inhibited IL-1beta and nitric oxide production by HD11 cells induced by different sources of lipopolysaccharides (LPS). N-terminal truncated CATH-2 derived peptides maintained the capacity to selectively induce chemokine transcription, but despite their high LPS affinity several analogs lacked LPS-neutralizing capacity. Substitution of phenylalanine residues by tryptophan introduced endotoxin neutralization capacity in inactive truncated CATH-2 derived peptides. In contrast, amino acid substitution of phenylalanine by tyrosine abrogated endotoxin neutralization activity of CATH-2 analogs. These findings support a pivotal role for aromatic residues in peptide-mediated endotoxin neutralization by CATH-2 analogs and were shown to be independent of LPS affinity. The capacity to modulate chemokine production and dampen endotoxin-induced pro-inflammatory responses in chicken immune cells implicates that small CATH-2 based peptides could serve as leads for the design of CATH-2 based immunomodulatory anti infectives. PMID- 26848846 TI - A case of percutaneous coronary intervention for treatment of iatrogenic chronic total occlusion of the left circumflex artery after mitral valve repair. AB - A 55-year-old man had undergone mitral annuloplasty for mitral regurgitation with posterior mitral prolapse 3 years prior. He was examined at our hospital for dyspnea and fatigue. A coronary angiogram revealed iatrogenic chronic total occlusion (CTO) in the left circumflex coronary artery. We performed percutaneous coronary intervention (PCI) and successfully placed an everolimus-eluting stent. An intravascular ultrasound (IVUS) showed an impaired coronary artery at the occlusion site. To our knowledge, this is the first reported successful PCI for iatrogenic CTO after mitral valve repair. IVUS-guided PCI may help prevent complications in unusual CTO cases, such as coronary rupture. PMID- 26848848 TI - Advancing Biological Wastewater Treatment: Extended Anaerobic Conditions Enhance the Removal of Endocrine and Dioxin-like Activities. AB - Conventional activated sludge treatment of wastewater does not completely remove micropollutants. Here, extending anaerobic conditions may enhance biodegradation. To explore this, we combined iron-reducing or substrate-limiting and aerobic pilot-scale reactors directly at a wastewater treatment plant. To assess the removal of endocrine disrupting chemicals (EDCs) as group of micropollutants that adversely affects wildlife, we applied a bioanalytical approach. We used in vitro bioassays covering seven receptor-mediated mechanisms of action, including (anti)androgenicity, (anti)estrogenicity, retinoid-like, and dioxin-like activity. Untreated wastewater induced antiandrogenic, estrogenic, antiestrogenic, and retinoid-like activity. Full-scale as well as reactor-scale activated sludge treatment effectively removes the observed effects. Nevertheless, high antiandrogenic and minor dioxin-like and estrogenic effects persisted in the treated effluent that may still be environmentally relevant. The anaerobic post-treatment under substrate-limiting conditions resulted in an additional removal of endocrine activities by 17-40%. The anaerobic pre-treatment under iron-reducing conditions significantly enhanced the removal of the residual effects by 40-75%. In conclusion, this study demonstrates that a further optimization of biological wastewater treatment is possible. Here, implementing iron-reducing anaerobic conditions preceding aerobic treatment appears promising to improve the removal of receptor-mediated toxicity. PMID- 26848847 TI - A Comprehensive Entomological, Serological and Molecular Study of 2013 Dengue Outbreak of Swat, Khyber Pakhtunkhwa, Pakistan. AB - BACKGROUND: Aedes aegypti and Aedes albopictus play a fundamental role in transmission of dengue virus to humans. A single infected Aedes mosquito is capable to act as a reservoir/amplifier host for dengue virus and may cause epidemics via horizontal and vertical modes of dengue virus (DENV) transmission. The present and future dengue development can be clarified by understanding the elements which help the dissemination of dengue transmission. The current study deals with molecular surveillance of dengue in addition to ecological and social context of 2013 dengue epidemics in Swat, Pakistan. METHODS: Herein, we reported dengue vectors surveillance in domestic and peridomistic containers in public and private places in 7 dengue epidemic-prone sites in District Swat, Pakistan from July to November 2013. Using the Flaviviruses genus-specific reverse transcriptase (RT) semi nested-PCR assay, we screened blood samples (N = 500) of dengue positive patients, 150 adult mosquito pools and 25 larval pools. RESULTS: The 34 adult and 7 larval mosquito pools were found positive. The adult positive pools comprised 30 pools of Ae. aegypti and 4 pools of Ae. albopictus, while among the 7 larval pools, 5 pools of Ae. aegypti and 2 pools of Ae. albopictus were positive. The detected putative genomes of dengue virus were of DENV-2 (35% in 14 mosquito pools & 39% in serum) and DENV-3 (65% in 27 mosquito pools & 61% in serum). The higher vector density and dengue transmission rate was recorded in July and August (due to favorable conditions for vector growth). About 37% of Ae. aegpti and 34% Ae. albopictus mosquitoes were collected from stagnant water in drums, followed by drinking water tanks (23% & 26%), tires (20% & 18%) and discarded containers (10% & 6%). Among the surveyed areas, Saidu was heavily affected (26%) by dengue followed by Kanju (20% and Landikas (12%). The maximum infection was observed in the age group of <15 (40%) followed by 15-45 (35%) and >45 (25%) years and was more in males (55.3%) as compare to females (44.7%). The increase in vector mosquito density and the subsequent viral transmission was determined by a complex interplay of ecological, biological and social factors. CONCLUSION: The suitable environmental conditions and discriminable role of Aedes through trans-ovarial transmission of DENV is indispensable in the recent geographic increase of dengue in Pakistan. Climate change affects the survival and dispersion of vectors as well as the transmission rates of dengue. Control of Aedes mosquitoes (vectors) and elimination of breeding sources must be emphasized and prioritized. Such actions may not only reduce the risk of dengue transmission during epidemics, but also minimize the chances of dengue viruses establishment in new (non endemic) areas of the region. PMID- 26848849 TI - High-Throughput Method for Automated Colony and Cell Counting by Digital Image Analysis Based on Edge Detection. AB - Counting cells and colonies is an integral part of high-throughput screens and quantitative cellular assays. Due to its subjective and time-intensive nature, manual counting has hindered the adoption of cellular assays such as tumor spheroid formation in high-throughput screens. The objective of this study was to develop an automated method for quick and reliable counting of cells and colonies from digital images. For this purpose, I developed an ImageJ macro Cell Colony Edge and a CellProfiler Pipeline Cell Colony Counting, and compared them to other open-source digital methods and manual counts. The ImageJ macro Cell Colony Edge is valuable in counting cells and colonies, and measuring their area, volume, morphology, and intensity. In this study, I demonstrate that Cell Colony Edge is superior to other open-source methods, in speed, accuracy and applicability to diverse cellular assays. It can fulfill the need to automate colony/cell counting in high-throughput screens, colony forming assays, and cellular assays. PMID- 26848851 TI - Non-hormonal and hormonal intrauterine contraception: survey of patients' perceptions in four Latin American countries. AB - OBJECTIVES: This study sought to understand women's perceived barriers to the use of hormonal and non-hormonal intrauterine contraception in Latin America. METHODS: We developed an online survey for women in Argentina, Brazil, Colombia and Mexico who were seeking contraception. The questions aimed at evaluating patient awareness of negative stories and statements, as well as perceived barriers to the copper intrauterine device (IUD) and the levonorgestrel-releasing intrauterine system (LNG-IUS). RESULTS: The survey was mailed to 2300 women. A total of 1953 responses were received from Argentina (n = 465), Brazil (n = 380), Colombia (n = 613) and Mexico (n = 495). More women reported having heard negative stories about the copper IUD than about the LNG-IUS. More women believed that the copper IUD, rather than the LNG-IUS, was suitable only for those who had already had children. More women believed that weight gain (14.3% vs. 38.2%; p < 0.001), mood swings (14.1% vs. 38.7%; p < 0.001) and infertility (16.3% vs. 19.9%; p = 0.016) were possible side effects of the LNG-IUS. By contrast, more women believed that abortion (36% vs. 22.7%; p < 0.001), pelvic infections (42.1% vs. 15.7%; p < 0.001) and ectopic pregnancy (43.5% vs 23.5%; p < 0.001) were side effects more associated with the copper IUD. More believed the copper IUD was associated with less pain during placement and removal compared with the LNG-IUS (42.8% vs. 31.2%; p < 0.001). The perception of increased risk of contracting a sexual transmitted disease did not differ between the methods (IUD vs. LNG-IUS, 21.7% vs. 20.3%; p = 0.388). CONCLUSIONS: Respondents to a web-based survey in four Latin American countries have misperceptions regarding the adverse effects and risks of intrauterine contraception, which may hamper the use of these safe and efficient contraceptive methods. Education about the true risks and benefits involved is fundamental to improving patient acceptance and compliance as well as reducing unplanned pregnancies and unsafe abortions. PMID- 26848850 TI - The Effect of Haemodialysis Access Types on Cardiac Performance and Morbidities in Patients with Symptomatic Heart Disease. AB - BACKGROUND: Little is known about whether the arteriovenous type haemodialysis access affects cardiac function and whether it is still advantageous to the uremic patient with symptomatic heart disease. METHODS: We conducted a retrospective comparative study. Patients with heart disease and end-stage renal disease that had a new chronic access created between January 2007 and December 2008 and met the inclusion criteria were assessed. The endpoint was major adverse event (MAE)-free survivals of arteriovenous access (AVA) and tunneled cuffed double-lumen central venous catheter (CVC) groups. Whether accesses worsened heart failure was also evaluated. RESULTS: There were 43 CVC patients and 60 AVA patients. The median follow-up time from access creation was 27.6 months (IQR 34.7, 10.9~45.6). Although CVC patients were older than AVA patients (median age 78.0, IQR 14.0 vs. 67.5, IQR 16.0, respectively, p = .009), they manifested non inferior MAE-free survival (mean 17.1, 95% CI 10.3~24.0 vs. 12.9, 95% CI 8.5~17.4 months in CVC and AVA patients, respectively, p = .290). During follow-up, more patients in the AVA group than in the CVC group deteriorated in heart failure status (35 of 57 vs. 10 of 42, respectively, odds ratio 5.1, p < .001). Preoperative-postoperative pairwise comparison of echocardiographic scans revealed an increased number of abnormal findings in the AVA group (Z = 3.91, p < .001), but not in the CVC group. CONCLUSIONS: In patients with both symptomatic heart disease and end stage renal disease (ESRD), CVC patients showed non inferior MAE-free survival in comparison to those in the AVA group. AV type access could deteriorate heart failure. Accordingly, uremic patients with symptomatic heart disease are not ideal candidates for AV type access creation. PMID- 26848852 TI - Vision in Flies: Measuring the Attention Span. AB - A visual stimulus at a particular location of the visual field may elicit a behavior while at the same time equally salient stimuli in other parts do not. This property of visual systems is known as selective visual attention (SVA). The animal is said to have a focus of attention (FoA) which it has shifted to a particular location. Visual attention normally involves an attention span at the location to which the FoA has been shifted. Here the attention span is measured in Drosophila. The fly is tethered and hence has its eyes fixed in space. It can shift its FoA internally. This shift is revealed using two simultaneous test stimuli with characteristic responses at their particular locations. In tethered flight a wild type fly keeps its FoA at a certain location for up to 4s. Flies with a mutation in the radish gene, that has been suggested to be involved in attention-like mechanisms, display a reduced attention span of only 1s. PMID- 26848853 TI - Fluorescence In Vivo Hybridization (FIVH) for Detection of Helicobacter pylori Infection in a C57BL/6 Mouse Model. AB - INTRODUCTION: In this study, we applied fluorescence in vivo hybridization (FIVH) using locked nucleic acid (LNA) probes targeting the bacterial rRNA gene for in vivo detection of H. pylori infecting the C57BL/6 mouse model. A previously designed Cy3_HP_LNA/2OMe_PS probe, complementary to a sequence of the H. pylori 16S rRNA gene, was used. First, the potential cytotoxicity and genotoxicity of the probe was assessed by commercial assays. Further, the performance of the probe for detecting H. pylori at different pH conditions was tested in vitro, using fluorescence in situ hybridization (FISH). Finally, the efficiency of FIVH to detect H. pylori SS1 strain in C57BL/6 infected mice was evaluated ex vivo in mucus samples, in cryosections and paraffin-embedded sections by epifluorescence and confocal microscopy. RESULTS: H. pylori SS1 strain infecting C57BL/6 mice was successfully detected by the Cy3_HP_LNA/2OMe_PS probe in the mucus, attached to gastric epithelial cells and colonizing the gastric pits. The specificity of the probe for H. pylori was confirmed by microscopy. CONCLUSIONS: In the future this methodology can be used in combination with a confocal laser endomicroscope for in vivo diagnosis of H. pylori infection using fluorescent LNA probes, which would be helpful to obtain an immediate diagnosis. Our results proved for the first time that FIVH method is applicable inside the body of a higher-order animal. PMID- 26848855 TI - Long-term follow-up after ESS and balloon sinuplasty: Comparison of symptom reduction and patient satisfaction. AB - CONCLUSION: This is the first controlled study of balloon sinuplasty's long-term efficacy with the follow-up time over 5 years. The results are in accordance with a previous 2-year-follow-up study. Both techniques retained the efficacy and patient satisfaction on average 6 years after the surgery. BACKGROUND: Endoscopic sinus surgery (ESS) and balloon sinuplasty are considered as a treatment for chronic rhinosinusitis (CRS) after a failure of conservative therapy. High cost and lack of long-term follow-up studies restrain the use of balloon sinuplasty. OBJECTIVE: The aim of this study was to compare long-term efficacy and satisfaction in CRS patients who had undergone maxillary sinus operation with either balloon sinuplasty or ESS technique. Previous or additional sinonasal operations were exclusion criteria. MATERIALS AND METHODS: Study patients were recruited from 208 CRS-patients who underwent either ESS or balloon sinuplasty. Patients with nasal polyposis (gradus >= 2), previous sinonasal surgery, unilateral disease, or immune deficiency were excluded. Altogether 45 patients in the ESS group and 40 patients in the balloon group were included. Of these, 30 and 28, respectively, answered to a phone interview held on average 6 years after primary surgery. Symptom reduction and long-term satisfaction were evaluated by using symptom scores of 19 parameters altogether. RESULTS: Both groups experienced improvement in symptoms and were equally satisfied with the operation. The number of patient-reported acute exacerbations was higher among the balloon dilated patients. Also, the reduction of thick nasal discharge was less evident in the balloon sinuplasty group. Four patients in the balloon sinuplasty group underwent revision surgery. There were no revisions in the ESS group. PMID- 26848854 TI - Recruitment of Saccharomyces cerevisiae Cmr1/Ydl156w to Coding Regions Promotes Transcription Genome Wide. AB - Cmr1 (changed mutation rate 1) is a largely uncharacterized nuclear protein that has recently emerged in several global genetic interaction and protein localization studies. It clusters with proteins involved in DNA damage and replication stress response, suggesting a role in maintaining genome integrity. Under conditions of proteasome inhibition or replication stress, this protein localizes to distinct sub-nuclear foci termed as intranuclear quality control (INQ) compartments, which sequester proteins for their subsequent degradation. Interestingly, it also interacts with histones, chromatin remodelers and modifiers, as well as with proteins involved in transcription including subunits of RNA Pol I and Pol III, but not with those of Pol II. It is not known whether Cmr1 plays a role in regulating transcription of Pol II target genes. Here, we show that Cmr1 is recruited to the coding regions of transcribed genes of S. cerevisiae. Cmr1 occupancy correlates with the Pol II occupancy genome-wide, indicating that it is recruited to coding sequences in a transcription-dependent manner. Cmr1-enriched genes include Gcn4 targets and ribosomal protein genes. Furthermore, our results show that Cmr1 recruitment to coding sequences is stimulated by Pol II CTD kinase, Kin28, and the histone deacetylases, Rpd3 and Hos2. Finally, our genome-wide analyses implicate Cmr1 in regulating Pol II occupancy at transcribed coding sequences. However, it is dispensable for maintaining co-transcriptional histone occupancy and histone modification (acetylation and methylation). Collectively, our results show that Cmr1 facilitates transcription by directly engaging with transcribed coding regions. PMID- 26848856 TI - Creating Protected Areas on Public Lands: Is There Room for Additional Conservation? AB - Most evaluations of the effectiveness of PAs have relied on indirect estimates based on comparisons between protected and unprotected areas. Such methods can be biased when protection is not randomly assigned. We add to the growing literature on the impact of PAs by answering the following research questions: What is the impact of Chilean PAs on deforestation which occurred between 1986 and 2011? How do estimates of the impact of PAs vary when using only public land as control units? We show that the characteristics of the areas in which protected and unprotected lands are located differ significantly. To satisfactorily estimate the effects of PAs, we use matching methods to define adequate control groups, but not as in previous research. We construct control groups using separately non protected private areas and non-protected public lands. We find that PAs avoid deforestation when using unprotected private lands as valid controls, however results show no impact when the control group is based only on unprotected public land. Different land management regimes, and higher levels of enforcement inside public lands may reduce the opportunity to add additional conservation benefits when the national systems for PAs are based on the protection of previously unprotected public lands. Given that not all PAs are established to avoid deforestation, results also admit the potential for future studies to include other outcomes including forest degradation (not just deforestation), biodiversity, wildlife, primary forests (not forests in general), among others. PMID- 26848857 TI - Genetic variants in complement pathway and ARMS2/HTRA1 genes and risk of age related macular degeneration in a homogeneous population from central Greece. PMID- 26848858 TI - Assessment of pelvic floor muscles in women with deep endometriosis. AB - PURPOSE: To assess function and prevalence of spasms and trigger points of the pelvic floor muscles in women with deep endometriosis. METHODS: One hundred and four (104) patients were assessed. Group 1 (G1) was composed of 52 subjects diagnosed with deep endometriosis proven by magnetic resonance imaging (MRI); Group 2 (G2) was composed of 52 women with no signs of endometriosis. Subjects from both G1 and G2 were seen at the Division of Pelvic Pain and Endometriosis and at Center for Prevention of Sexually Transmitted Diseases, both at Federal University of Sao Paulo (UNIFESP), respectively. A full physical therapy evaluation was carried out, including medical history, presence of dyspareunia and physical examination, which included detailed evaluation of pelvic floor muscles and occurrence of muscle spasm, trigger point and muscle function. RESULTS: The average age of the subjects in the study group was 36.4 and 30.9 years in the control group (p = 0.002). A greater prevalence of deep dyspareunia was found in the subjects in the endometriosis group when compared to the control group (p = 0.010). Women in G1 had higher prevalence of muscle spasms. In this group, 53.9 % had spasms-compared to only 17.3 % of women in G2 (p < 0.001). On the other hand, no significant difference between the groups (p = 0.153) was found while searching for the presence of trigger points. CONCLUSION: Women with deep endometriosis have increased prevalence of pelvic floor muscle spasms when compared to the control group. PMID- 26848859 TI - Modeling the dyadic effects of parenting, stress, and coping on parent-child communication in families tested for hereditary breast-ovarian cancer risk. AB - Genetic testing for BRCA genes, associated with hereditary breast-ovarian cancer risk, is an accepted cancer control strategy. BRCA genetic testing has both medical and psychosocial implications for individuals seeking testing and their family members. However, promoting open and adaptive communication about cancer risk in the family is challenging for parents of minor children. Using prospective data collected from mothers undergoing BRCA genetic testing and their untested co-parents (N = 102 parenting dyads), we examined how maternal and co parent characteristics independently and conjointly influenced the overall quality of parent-child communication with minor children. Statistical associations were tested in accordance with the Actor-Partner Interdependence Model. Significant Actor effects were observed among mothers, such that open parent-child communication prior to genetic testing was positively associated with open communication 6 months following receipt of genetic test results; and among co-parents, more open parent-child communication at baseline and greater perceived quality of the parenting relationship were associated with more open parent-child communication at follow-up. Partner effects were also observed: co parents' baseline communication and confidence in their ability to communicate with their minor children about genetic testing was positively associated with open maternal parent-child communication at follow-up. These results demonstrate that for families facing the prospect of cancer genetic testing, perceptions and behaviors of both members of child-rearing couples have important implications for the overall quality of communication with their minor children, including communication about cancer risk. PMID- 26848860 TI - Therapeutic opportunities in Ewing sarcoma: EWS-FLI inhibition via LSD1 targeting. AB - Ewing sarcoma is an aggressive primary pediatric bone tumor, often diagnosed in adolescents and young adults. A pathognomonic reciprocal chromosomal translocation results in a fusion gene coding for a protein which derives its N terminus from a FUS/EWS/TAF15 (FET) protein family member, commonly EWS, and C terminus containing the DNA-binding domain of an ETS transcription factor, commonly FLI1. Nearly 85% of cases express the EWS-FLI protein which functions as a transcription factor and drives oncogenesis. As the primary genomic lesion and a protein which is not expressed in normal cells, disrupting EWS-FLI function is an attractive therapeutic strategy for Ewing sarcoma. However, transcription factors are notoriously difficult targets for the development of small molecules. Improved understanding of the oncogenic mechanisms employed by EWS-FLI to hijack normal cellular programming has uncovered potential novel approaches to pharmacologically block EWS-FLI function. In this review we examine targeting the chromatin regulatory enzymes recruited to conspire in oncogenesis with a focus on the histone lysine specific demethylase 1 (LSD1). LSD1 inhibitors are being aggressively investigated in acute myeloid leukemia and the results of early clinical trials will help inform the future use of LSD1 inhibitors in sarcoma. High LSD1 expression is observed in Ewing sarcoma patient samples and mechanistic and preclinical data suggest LSD1 inhibition globally disrupts the function of EWS-ETS proteins. PMID- 26848862 TI - FYN expression potentiates FLT3-ITD induced STAT5 signaling in acute myeloid leukemia. AB - FYN is a non-receptor tyrosine kinase belonging to the SRC family of kinases, which are frequently over-expressed in human cancers, and play key roles in cancer biology. SRC has long been recognized as an important oncogene, but little attention has been given to its other family members. In this report, we have studied the role of FYN in FLT3 signaling in respect to acute myeloid leukemia (AML). We observed that FYN displays a strong association with wild-type FLT3 as well as oncogenic FLT3-ITD and is dependent on the kinase activity of FLT3 and the SH2 domain of FYN. We identified multiple FYN binding sites in FLT3, which partially overlapped with SRC binding sites. To understand the role of FYN in FLT3 signaling, we generated FYN overexpressing cells. We observed that expression of FYN resulted in slightly enhanced phosphorylation of AKT, ERK1/2 and p38 in response to ligand stimulation. Furthermore, FYN expression led to a slight increase in FLT3-ITD-dependent cell proliferation, but potent enhancement of STAT5 phosphorylation as well as colony formation. We also observed that FYN expression is deregulated in AML patient samples and that higher expression of FYN, in combination with FLT3-ITD mutation, resulted in enrichment of the STAT5 signaling pathway and correlated with poor prognosis in AML. Taken together our data suggest that FYN cooperates with oncogenic FLT3-ITD in cellular transformation by selective activation of the STAT5 pathway. Therefore, inhibition of FYN, in combination with FLT3 inhibition, will most likely be beneficial for this group of AML patients. PMID- 26848861 TI - Tumor suppressor microRNAs are downregulated in myelodysplastic syndrome with spliceosome mutations. AB - Spliceosome mutations are frequently observed in patients with myelodysplastic syndromes (MDS). However, it is largely unknown how these mutations contribute to the disease. MicroRNAs (miRNAs) are small noncoding RNAs, which have been implicated in most human cancers due to their role in post transcriptional gene regulation. The aim of this study was to analyze the impact of spliceosome mutations on the expression of miRNAs in a cohort of 34 MDS patients. In total, the expression of 76 miRNAs, including mirtrons and splice site overlapping miRNAs, was accurately quantified using reverse transcriptase quantitative PCR. The majority of the studied miRNAs have previously been implicated in MDS. Stably expressed miRNA genes for normalization of the data were identified using GeNorm and NormFinder algorithms. High-resolution melting assays covering all mutational hotspots within SF3B1, SRSF2, and U2AF1 (U2AF35) were developed, and all detected mutations were confirmed by Sanger sequencing. Overall, canonical miRNAs were downregulated in spliceosome mutated samples compared to wild-type (P = 0.002), and samples from spliceosome mutated patients clustered together in hierarchical cluster analyses. Among the most downregulated miRNAs were several tumor suppressor miRNAs, including several let-7 family members, miR-423, and miR-103a. Finally, we observed that the predicted targets of the most downregulated miRNAs were involved in apoptosis, hematopoiesis, and acute myeloid leukemia among other cancer- and metabolic pathways. Our data indicate that spliceosome mutations may play an important role in MDS pathophysiology by affecting the expression of tumor suppressor miRNA genes involved in the development and progression of MDS. PMID- 26848863 TI - Clonal relationships in recurrent B-cell lymphomas. AB - Immunoglobulin (Ig) gene rearrangements remain largely unmodified during the clonal expansion of neoplastic cells. We investigated the clonal relationships between lymphoma components at diagnosis and at relapse by analyzing Ig gene rearrangements. A BIOMED-2 multiplex polymerase chain reaction (PCR) assay was performed in 27 patients using formalin-fixed paraffin embedded tissues, with subsequent cloning and sequencing of the amplified Ig genes in 17 patients. All 27 cases of primary and corresponding relapsed tumors showed monoclonal rearrangements of the Ig genes by BIOMED-2 PCR. Whereas IgVH or IgVK fragment lengths were identical in 8/27 pairs (30%), fragment lengths differed in 19/27 pairs (70%). In 17 cases analyzed by sequencing, an identical VDJ gene rearrangement was confirmed in 4/4 pairs (100%) with the same fragment lengths and in 10/13 pairs (77%) with different fragment lengths. Four of 17 primary lymphomas had multiple VDJ rearrangements, and three of them showed an unrelated relapse. Unrelated relapse was observed in 1/8 mantle cell lymphomas, 1/5 diffuse large B-cell lymphomas, and a large B cell lymphoma developed in a patient with a small lymphocytic lymphoma. Unrelated relapses developed after a longer disease free interval and tended to show poorer outcome compared with related relapse. In summary, relapse of a lymphoma from an unrelated clone is uncommon, but can occur in B-cell lymphomas. Clonal relationships should be determined by sequencing of the Ig genes, and not just by comparing the PCR product size. PMID- 26848864 TI - Exo70 is transcriptionally up-regulated by hepatic nuclear factor 4alpha and contributes to cell cycle control in hepatoma cells. AB - Exo70, a member of the exocyst complex, is involved in cell exocytosis, migration, invasion and autophagy. However, the expression regulation and function of Exo70 in hepatocellular carcinoma are still poorly understood. In this study, we found Exo70 expression in human hepatoma cells was greatly reduced after knocking down hepatic nuclear factor 4alpha (HNF4alpha), the most important and abundant transcription factor in liver. This regulation occurred at the transcriptional level but not post-translational level. HNF4alpha transactivated Exo70 promoter through directly binding to the HNF4alpha-response element in this promoter. Cell cycle analysis further revealed that down-regulation of HNF4alpha and Exo70 was essential to berberine-stimulated G2/M cell cycle arrest in hepatoma cells. Moreover, knocking down either Exo70 or HNF4alpha induced G2/M phase arrest of hepatoma cells. Exo70 acted downstream of HNF4alpha to stimulate G2/M transition via increasing Cdc2 expression. Together, our results identify Exo70 as a novel transcriptional target of HNF4alpha to promote cell cycle progression in hepatoma, thus provide a basis for the development of therapeutic strategies for hepatocellular carcinoma. PMID- 26848865 TI - CD93 and dystroglycan cooperation in human endothelial cell adhesion and migration adhesion and migration. AB - CD93 is a transmembrane glycoprotein predominantly expressed in endothelial cells. Although CD93 displays proangiogenic activity, its molecular function in angiogenesis still needs to be clarified. To get molecular insight into the biological role of CD93 in the endothelium, we performed proteomic analyses to examine changes in the protein profile of endothelial cells after CD93 silencing. Among differentially expressed proteins, we identified dystroglycan, a laminin binding protein involved in angiogenesis, whose expression is increased in vascular endothelial cells within malignant tumors. Using immunofluorescence, FRET, and proximity ligation analyses, we observed a close interaction between CD93 and beta-dystroglycan. Moreover, silencing experiments showed that CD93 and dystroglycan promoted endothelial cell migration and organization into capillary like structures. CD93 proved to be phosphorylated on tyrosine 628 and 644 following cell adhesion on laminin through dystroglycan. This phosphorylation was shown to be necessary for a proper endothelial migratory phenotype. Moreover, we showed that during cell spreading phosphorylated CD93 recruited the signaling protein Cbl, which in turn was phosphorylated on tyrosine 774. Altogether, our results identify a new signaling pathway which is activated by the cooperation between CD93 and dystroglycan and involved in the control of endothelial cell function. PMID- 26848866 TI - Naturally occurring basal core promoter A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma: a meta-analysis. AB - Basal core promoter (BCP) A1762T/G1764A dual mutations in hepatocarcinogenesis remain controversial. Published studies up to June 1, 2015 investigating the frequency of A1762T/G1764A dual mutations from chronic hepatitis B virus (HBV) infection, including hepatocellular carcinoma (HCC), were systematically identified. A total of 10,240 patients with chronic HBV infection, including 3729 HCC cases, were included in 52 identified studies. HCC patients had a higher frequency of BCP A1762T/G1764A dual mutations compared with asymptomatic HBsAg carriers (ASC) and patients with chronic hepatitis B (CHB) and liver cirrhosis (LC) (OR = 5.59, P < 0.00001; OR = 2.87, P < 0.00001; OR = 1.55, P = 0.02, respectively). No statistically significant difference was observed in the frequency of A1762T/G1764A dual mutations in cirrhotic HCC versus non-cirrhotic HCC patients (OR = 2.06, P = 0.05). Chronic HBV-infected patients and HCC patients with genotype B had a significantly lower risk of A1762T/G1764A dual mutations compared with patients with genotype C (OR = 0.30, P < 0.0001 and OR = 0.34, P = 0.04, respectively). In HBV genotype C subjects, A1762T/G1764A dual mutations contributed to significantly higher risk for HCC developing compared with non-mutation ones (OR = 3.47, P < 0.00001). In conclusion, A1762T/G1764A dual mutations increase the risk of HBV-related hepatocellular carcinoma, particularly in an HBV genotype C population, even without progression to cirrhosis. PMID- 26848867 TI - Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cells metastasis by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways. AB - Zoledronate is a standard treatment for preventing skeletal complications of osteoporosis and some types of cancer associated with bone metastases, but we little know whether the effect of zoledronate on metastasis of osteosarcoma. Here, we investigated the inhibitory effects of zoledronate on cell viability, motility, migration and invasion of 4 osteosarcoma cell lines (Saos2, MG-63, HOS and U2OS) by affecting cell morphology, epithelial-mesenchymal transition (EMT) and cytoskeletal organization as well as induction of E-cadherin and reduction of N-cadherin with activation of transcription factors Slug and Twist, especially in U2OS cells. Zoledronate decreased JNK and p38 phosphorylation and upper streams of focal adhesion kinase (FAK) and Src to suppress the motility, invasiveness and migration of U2OS cells. In addition to zoledronate-inhibited Rho A and Cdc42 membrane translocation and GTPgammaS activities, the anti-metastatic effects in U2OS cells including inhibition of adhesion were reversed by geranylgeraniol, but not farnesol. In conclusion, Zoledronate blocks geranylgeranylation not farnesylation to suppress human osteosarcoma U2OS cell-matrix and cell-cell interactions, migration potential, the invasive activity, and the adhesive ability by EMT via Rho A activation and FAK-inhibited JNK and p38 pathways. PMID- 26848868 TI - Regulation of androgen receptor splice variant AR3 by PCGEM1. AB - The androgen receptor (AR) is required for prostate development and is also a major driver of prostate cancer pathogenesis. Thus androgen deprivation therapy (ADT) is the mainstay of treatment for advanced prostate cancer. However, castration resistance due to expression of constitutively active AR splice variants is a significant challenge to prostate cancer therapy; little is known why effectiveness of ADT can only last for a relatively short time. In the present study, we show that PCGEM1 interacts with splicing factors heterogeneous nuclear ribonucleoprotein (hnRNP) A1 and U2AF65, as determined by RNA precipitation and Western blot, suggesting a role for PCGEM1 in alternative splicing. In support of this possibility, PCGEM1 is correlated with AR3, a predominant and clinically important form of AR splice variants in prostate cancer. Moreover, androgen deprivation (AD) induces PCGEM1 and causes its accumulation in nuclear speckles. Finally, we show that the AD-induced PCGEM1 regulates the competition between hnRNP A1 and U2AF65 for AR pre-mRNA. AD promotes PCGEM1 to interact with both hnRNP A1 and U2AF65 with different consequences. While the interaction of PCGEM1 with hnRNP A1 suppresses AR3 by exon skipping, its interaction with U2AF65 promotes AR3 by exonization. Together, we demonstrate an AD-mediated AR3 expression involving PCGEM1 and splicing factors. PMID- 26848869 TI - Transtinib, a potent tyrosine kinase inhibitor inhibits L858R/T790M mutant NSCLC cell lines and xenografts. AB - Non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations initially respond well to the EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. However, clinical efficacy is limited by the development of resistance. In most cases, this resistance is in the form of the T790M mutation. Here, we report the design, synthesis and biochemical evaluation of a novel series of irreversible EGFR tyrosine kinase inhibitors (EGFR-TKIs) that are derived from the anilinoquinazoline scaffold. Guided by molecular modeling, this series of analogs was evolved to target a cysteine residue in the ATP binding site via covalent bond formation and to achieve high levels of anti-tumor activity in cell cultures and in xenografts. The most promising compound 13c ((E) -N - (4 - (4 - (3-fluorobenzyloxy) -3- chlorophenylamino) -7-ethoxyquinazolin-6-yl) -3- ((S) -pyrrolidin-2 yl)acrylamide, which we named Transtinib) displayed strong anti-proliferative activity against the H1975 and A431 cell lines with IC50 values of 34 nM and 62 nM, respectively. In xenograft models, Transtinib significantly decreases tumor size for a prolonged period of time. These results suggest that Transtinib is a potential cancer therapeutic drug lead for the inhibition of mutant EGFR to overcome the development of resistance. PMID- 26848871 TI - Simple Technique for Transvaginal Aspiration of a Tubo-Ovarian Abscess. AB - Large tubo-ovarian abscesses (TOAs) usually require drainage or operative management in addition to antibiotics. All previous reports of transvaginal aspiration have been described utilizing a needle/biopsy guidance system, which may not be available to many obstetrician/gynecologists. We present a simple technique for transvaginal drainage of large TOAs using a long angiocath needle under transabdominal ultrasound guidance in a patient in whom percutaneous drainage and operative management were not ideal options. This is the first report about the use of this technique. Our patient has recovered fully and remains free of infection 10 months later. Providers should consider this technique when other modalities are not available, are of questionable benefit, or present high potential for additional complications. PMID- 26848870 TI - A humanized antibody for imaging immune checkpoint ligand PD-L1 expression in tumors. AB - Antibodies targeting the PD-1/PD-L1 immune checkpoint lead to tumor regression and improved survival in several cancers. PD-L1 expression in tumors may be predictive of response to checkpoint blockade therapy. Because tissue samples might not always be available to guide therapy, we developed and evaluated a humanized antibody for non-invasive imaging of PD-L1 expression in tumors. Radiolabeled [111In]PD-L1-mAb and near-infrared dye conjugated NIR-PD-L1-mAb imaging agents were developed using the mouse and human cross-reactive PD-L1 antibody MPDL3280A. We tested specificity of [111In]PD-L1-mAb and NIR-PD-L1-mAb in cell lines and in tumors with varying levels of PD-L1 expression. We performed SPECT/CT imaging, biodistribution and blocking studies in NSG mice bearing tumors with constitutive PD-L1 expression (CHO-PDL1) and in controls (CHO). Results were confirmed in triple negative breast cancer (TNBC) (MDAMB231 and SUM149) and non small cell lung cancer (NSCLC) (H2444 and H1155) xenografts with varying levels of PD-L1 expression. There was specific binding of [111In]PD-L1-mAb and NIR-PD-L1 mAb to tumor cells in vitro, correlating with PD-L1 expression levels. In mice bearing subcutaneous and orthotopic tumors, there was specific and persistent high accumulation of signal intensity in PD-L1 positive tumors (CHO-PDL1, MDAMB231, H2444) but not in controls. These results demonstrate that [111In]PD-L1 mAb and NIR-PD-L1-mAb can detect graded levels of PD-L1 expression in human tumor xenografts in vivo. As a humanized antibody, these findings suggest clinical translation of radiolabeled versions of MPDL3280A for imaging. Specificity of NIR PD-L1-mAb indicates the potential for optical imaging of PD-L1 expression in tumors in relevant pre-clinical as well as clinical settings. PMID- 26848872 TI - Effects of a multifactorial injury prevention intervention in physical education teachers: A randomized controlled trial. AB - Physical education (PE) teachers are at a high risk of musculoskeletal sports or work-related injuries because of the physical activity as inherent part of their profession. Such injuries have a negative impact on work and leisure time activities, and effective injury prevention interventions are needed. The present study aimed at testing the effectiveness of an injury prevention intervention that was developed and optimized according to PE teachers' wishes and values. Fifty-five PE teachers were randomly assigned to intervention or control group. Intervention group teachers engaged in two days of training during which they familiarized with eight injury prevention strategies (seven intrinsic and one extrinsic). A special feature of the intervention was that the way of delivery was based on the self-determination theory in order to stimulate participants' motivation to adhere to the proposed strategies. Prospective registrations during one school year were conducted concerning injuries and preventive behaviours. Results showed that the intervention group teachers had a lower number of injuries per 1000 h time of exposure (TOE) than the controls (INT: 0.49, CON: 1.14 injuries/1000 h TOE, OR: 2.32, 95% CI: 1.06-5.07), and applied a broader variety of strategies including dynamic and static stretching, core stability, balance and strength training, when compared to the controls who mainly engaged in warming-up. In conclusion, with the same amount of time, an injury reduction was found in PE teachers through a more balanced use of provided preventive strategies. PMID- 26848873 TI - Uremic Toxicity-Induced Eryptosis and Monocyte Modulation: The Erythrophagocytosis as a Novel Pathway to Renal Anemia. AB - BACKGROUND: We tested the effect of uremia on red blood cell (RBC) eryptosis, CD14++/CD16+ monocytes and erythrophagocytosis. DESIGN: RBC and monocytes from chronic kidney disease (CKD) stages 3/4 (P-CKD3/4) or hemodialysis (HD) patients and healthy controls (HCs) cells incubated with sera pools from patients with CKD stages 2/3 (S-CKD2/3) or 4/5 (S-CKD4/5) were evaluated to assess eryptosis, monocyte phenotypes and reactive oxygen species (ROS) by cytometer. Erythrophagocytosis was evaluated by subsequent co-incubation of preincubated HC monocytes and autologous-RBC. RESULTS: HC-eryptosis (1.3 +/- 0.9%) was lower than in HD (4.3 +/- 0.5%) and HC-RBC incubated with S-CKD4/5 (5.6 +/- 1%). CD14++/CD16+ were augmented in P-CKD3/4 (34.6 +/- 8%) and HC-monocytes incubated with S-CKD4/5 (26.4 +/- 7%) than in HC (5.4 +/- 1%). In these cells, ROS was increased (44.5 +/- 9%; control 9.6 +/- 2%) and inhibited by N-acetylcysteine (25 +/- 13%). Erythrophagocytosis was increased in CD14++/CD16+ (60.8 +/- 10%) than in CD14++/CD16- (15.5 +/- 2%). CONCLUSIONS: Sera pools from CKD patients increase eryptosis and promote a proinflammatory monocyte phenotype. Both processes increased erythrophagocytosis, thereby suggesting a novel pathway for renal anemia. PMID- 26848874 TI - Structural Insights into Mycobacterium tuberculosis Rv2671 Protein as a Dihydrofolate Reductase Functional Analogue Contributing to para-Aminosalicylic Acid Resistance. AB - Mycobacterium tuberculosis (Mtb) Rv2671 is annotated as a 5-amino-6-ribitylamino 2,4(1H,3H)-pyrimidinedione 5'-phosphate (AROPP) reductase (RibD) in the riboflavin biosynthetic pathway. Recently, a strain of Mtb with a mutation in the 5' untranslated region of Rv2671, which resulted in its overexpression, was found to be resistant to dihydrofolate reductase (DHFR) inhibitors including the anti Mtb drug para-aminosalicylic acid (PAS). In this study, a biochemical analysis of Rv2671 showed that it was able to catalyze the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF), which explained why the overexpression of Rv2671 was sufficient to confer PAS resistance. We solved the structure of Rv2671 in complex with the NADP(+) and tetrahydrofolate (THF), which revealed the structural basis for the DHFR activity. The structures of Rv2671 complexed with two DHFR inhibitors, trimethoprim and trimetrexate, provided additional details of the substrate binding pocket and elucidated the differences between their inhibitory activities. Finally, Rv2671 was unable to catalyze the reduction of AROPP, which indicated that Rv2671 and its closely related orthologues are not involved in riboflavin biosynthesis. PMID- 26848875 TI - Molecular docking and 3D-QSAR studies on the glucocorticoid receptor antagonistic activity of hydroxylated polychlorinated biphenyls. AB - The glucocorticoid receptor (GR) antagonistic activities of hydroxylated polychlorinated biphenyls (HO-PCBs) were recently characterised. To further explore the interactions between HO-PCBs and the GR, and to elucidate structural characteristics that influence the GR antagonistic activity of HO-PCBs, molecular docking and three-dimensional quantitative structure-activity relationship (3D QSAR) studies were performed. Comparative molecular similarity indices analysis (CoMSIA) was performed using both ligand- and receptor-based alignment schemes. Results generated from the receptor-based model were found to be more satisfactory, with q(2) of 0.632 and r(2) of 0.931 compared with those from the ligand-based model. Some internal validation strategies (e.g. cross-validation analysis, bootstrapping analysis and Y-randomisation) and an external validation method were used respectively to further assess the stability and predictive ability of the derived model. Graphical interpretation of the model provided some insights into the structural features that affected the GR antagonistic activity of HO-PCBs. Molecular docking studies revealed that some key residues were critical for ligand-receptor interactions by forming hydrogen bonds (Glu540) and hydrophobic interactions with ligands (Ile539, Val543 and Trp577). Although CoMSIA sometimes depends on the alignment of the molecules, the information provided is beneficial for predicting the GR antagonistic activities of HO-PCB homologues and is helpful for understanding the binding mechanisms of HO-PCBs to GR. PMID- 26848876 TI - Negative mood disrupts self- and reward-biases in perceptual matching. AB - There are established effects of self- and reward-biases even on simple perceptual matching tasks [Sui, J., He, X., & Humphreys, G. W. (2012). Perceptual effects of social salience: Evidence from self-prioritization effects on perceptual matching. Journal of Experimental Psychology, Human Perception and Performance, 38, 1105-1117]; however we know little about whether these biases can be modulated by particular interventions, and whether the biases then change in the same way. Here we assessed how the biases alter under conditions designed to induce negative mood. We had participants read a list of self-related negative or neutral mood statements [Velten, E. (1968). A laboratory task for induction of mood states. Behavior Research and Therapy, 6, 473-482] and also listen for 10 min to a passage of negative or neutral music, prior to carrying out perceptual matching with shapes associated to personal labels (self or stranger) or reward (L12 or L1). Responses to the self- and high-reward-associated shapes were selectively slower and less sensitive (d') following the negative mood induction procedures, and the decrease in mood correlated with decreases in the reaction time bias across "high saliency" (self and high-reward) stimuli. We suggest that negative mood may decrease self- and reward-biases through reducing attention to salient external stimuli. PMID- 26848877 TI - Selected volatile organic compounds as biomarkers for exposure to tobacco smoke. AB - Cutoff levels on the scales for benzene, ethylbenzene, toluene, styrene, o-xylene and m/p-xylene in blood were developed to classify smokers from non-smokers. Self reported smoking during the last 5 d was used as the true smoking status. Receiver operating characteristics methods that minimized the difference between specificity and sensitivity were used to develop these cutoffs. Data from National Health and Nutrition Examination Survey for the cycle 2005-2006 were used for this purpose. For the total population, a cutoff of 0.038 ng/ml for benzene was able to classify smokers from non-smokers with a sensitivity of 83.6% and specificity of 83.7%. PMID- 26848878 TI - Erratum. PMID- 26848879 TI - Clinical Manifestations and Outcome of Syphilitic Uveitis. AB - PURPOSE: To analyze visual outcome, effectiveness of various modes of antibiotic treatment, and prognostic factors in patients with serologically proven syphilitic uveitis. METHODS: The clinical records of 85 patients (139 eyes) diagnosed with syphilitic uveitis between 1984 and 2013 at tertiary centers in The Netherlands were retrospectively analyzed. RESULTS: Mean age was 47 years (range, 27-73 years), 82.4% were male. HIV positivity was found in 28 (35.9%) patients; 13 were newly diagnosed. Most patients had pan (45.9%) or posterior (31.8%) uveitis. On average, logMAR visual acuity (VA) improved significantly from 0.55 at the start of syphilis treatment to 0.34 at 1 month and to 0.27 at 6 months follow-up. Most patients (86.7%) reached disease remission. No differences in efficacy between the various treatment regimens were found. A high logMAR VA at the start of syphilis treatment and a treatment delay of more than 12 weeks were prognostic for a high logMAR VA at 6 months follow-up. Chronicity was not related to any form of treatment, HIV status, or Venereal Disease Research Laboratory test outcome. CONCLUSIONS: In this large cohort of 85 patients with syphilitic uveitis, visual outcomes were favorable in the majority of cases. Visual outcome was dependent on VA at the start of syphilis treatment and treatment delay. PMID- 26848880 TI - Local Modulation of Retinal Vein Tone. AB - PURPOSE: To determine whether vascular tone of isolated porcine retinal veins can be modulated by tissue-generated vasoactive factors such as endothelin-1 and adenosine. Such information may be useful in understanding the role of the retinal veins in regulating blood flow, and also provide a model for investigating new hypotheses suggesting a role for vasoactive factors in retinal vascular diseases such as retinal vein occlusion. METHODS: An isolated perfused retinal vein preparation was used for this study. Segments of porcine retinal veins were dissected, cannulated, and perfused, and their diameter was monitored during vasoactive agent application of increasing doses of endothelin-1 (10(-12) 10(-8) M) or adenosine (10(-10)-10(-4) M). Adenosine (10(-6) M) was also applied on veins during preconstriction with endothelin-1 (10(-8) M). The significance of any induced change in vessel diameter was assessed in relation to the baseline vessel diameter prior to any drug delivery. RESULTS: Dose-dependent vasocontractile responses were induced by endothelin-1 administration. Endothelin 1 produced a significant contraction at doses of 10-11 M and above. At 10(-8) M the maximal endothelin-1-induced contractions were to 70.2 +/- 2.1% of baseline. Adenosine produced a dose-dependent dilation reaching 113.0 +/- 2.4% at 10(-4) M. Adenosine (10(-6) M) induced a significant dilation in endothelin-1 (10(-8) M) contracted vessels. CONCLUSIONS: Porcine retinal veins can be modulated by both vasocontraction and vasodilation agents, suggesting that the retinal veins may play a regulatory role in the retinal circulation, particularly in regard to the capillary pressure upstream from the draining retinal veins. To our knowledge, this is the first study of vasoactivity in isolated perfused retinal veins, providing an opportunity to study the direct vasoactive effects of specific vasoactive agents. PMID- 26848881 TI - Structure-Function Relationship in Glaucoma Patients With Parafoveal Versus Peripheral Nasal Scotoma. AB - PURPOSE: We evaluated whether the structure-function relationship in glaucoma patients with parafoveal scotoma or peripheral scotoma differs with the use of frequency doubling technology (FDT) or short-wavelength automated perimetry (SWAP) compared to standard automated perimetry (SAP). METHODS: Glaucoma patients with isolated parafoveal scotoma (PFS) within the central 10 degrees of fixation in 1 hemifield and those with an isolated peripheral nasal step (PNS) within the nasal periphery outside 10 degrees of fixation in one hemifield were studied. Peripapillary retinal nerve fiber layer (RNFL) thickness was measured using spectral-domain optical coherence tomography. The topographic relationships between structure and function were investigated. RESULTS: In the PNS group, superotemporal (r(2) = 0.300, P = 0.001) and inferotemporal (r(2) = 0.302, P = 0.001) RNFL thickness showed significant correlations with the corresponding visual field (VF) sensitivity using linear regression model in SAP. In the PFS group, temporal RNFL thickness was not correlated with nasal mean sensitivity (MS) on SAP (r(2) = 0.103, P = 0.065). Using FDT, however, the temporal RNFL thickness was correlated with nasal MS in the PFS group (r(2) = 0.277, P = 0.001). Using SWAP, the temporal RNFL thickness was not significantly associated with regional VF sensitivity in the PFS group (r(2) = 0.052, P = 0.192). CONCLUSIONS: In glaucoma with peripheral scotoma, the RNFL thickness was associated significantly with the corresponding VF loss in SAP, FDT, and SWAP. In eyes with PFS, however, the topographic structure-function relationships were not distinct with SAP or SWAP. Frequency doubling technology performed well in terms of structure-function correlation in glaucoma with PFS. PMID- 26848883 TI - Optical Manipulation and Spectroscopy Of Silicon Nanoparticles Exhibiting Dielectric Resonances. AB - We demonstrate that silicon (Si) nanoparticles with scattering properties exhibiting strong dielectric resonances can be successfully manipulated using optical tweezers. The large dielectric constant of Si has a distinct advantage over conventional colloidal nanoparticles in that it leads to enhanced trapping forces without the heating associated with metallic nanoparticles. Further, the spectral features of the trapped nanoparticles provide a unique marker for probing size, shape, orientation and local dielectric environment. We exploit these properties to investigate the trapping dynamics of Si nanoparticles with different dimensions ranging from 50 to 200 nm and aspect ratios between 0.4 and 2. The unique combination of spectral and trapping properties make Si nanoparticles an ideal system for delivering directed nanoscale sensing in a range of potential applications. PMID- 26848882 TI - siRNA-Mediated Knockdown of the mTOR Inhibitor RTP801 Promotes Retinal Ganglion Cell Survival and Axon Elongation by Direct and Indirect Mechanisms. AB - PURPOSE: To investigate, using in vivo and in vitro models, retinal ganglion cell (RGC) neuroprotective and axon regenerative effects and underlying mechanisms of siRTP801, a translatable small-interfering RNA (siRNA) targeting the mTOR negative regulator RTP801. METHODS: Adult rats underwent optic nerve (ON) crush (ONC) followed by intravitreal siRTP801 or control siRNA (siEGFP) every 8 days, with Brn3a+ RGC survival, GFAP+ reactive gliosis, and GAP43+ regenerating axons analyzed immunohistochemically 24 days after injury. Retinal cultures, prepared from uninjured animals or 5 days after ONC to activate retinal glia, were treated with siRTP801/controls in the presence/absence of rapamycin and subsequently assessed for RGC survival and neurite outgrowth, RTP801 expression, glial responses, and mTOR activity. Conditioned medium was analyzed for neurotrophin titers by ELISA. RESULTS: Intravitreal siRTP801 enabled 82% RGC survival compared to 45% with siEGFP 24 days after ONC, correlated with greater GAP43+ axon regeneration at 400 to 1200 MUm beyond the ONC site, and potentiated the reactive GFAP+ Muller glial response. In culture, siRTP801 had a direct RGC neuroprotective effect, but required GFAP+ activated glia to stimulate neurite elongation. The siRTP801-induced neuroprotection was significantly reduced, but not abolished, by rapamycin. The siRTP801 potentiated the production and release of neurotrophins NGF, NT-3, and BDNF, and prevented downregulation of RGC mTOR activity. CONCLUSIONS: The RTP801 knockdown promoted RGC survival and axon elongation after ONC, without increasing de novo regenerative sprouting. The neuroprotection was predominantly direct, with mTORC1-dependent and -independent components. Enhanced neurite/axon elongation by siRTP801 required the presence of activated retinal glia and was mediated by potentiated secretion of neurotrophic factors. PMID- 26848884 TI - Role of extracorporeal membrane oxygenation in adult respiratory failure: an overview. AB - Extracorporeal membrane oxygenation (ECMO) provides complete or partial support of the heart and lungs. Ever since its inception in the 1960s, it has been used across all age groups in the management of refractory respiratory failure and cardiogenic shock. While it has gained widespread acceptance in the neonatal and pediatric physician community, ECMO remains a controversial therapy for Acute Respiratory Distress Syndrome (ARDS) in adults. Its popularity was revived during the swine flu (H1N1) pandemic and advancements in technology have contributed to its increasing usage. ARDS continues to be a potentially devastating condition with significant mortality rates. Despite gaining more insights into this entity over the years, mechanical ventilation remains the only life-saving, yet potentially harmful intervention available for ARDS. ECMO shows promise in this regard by offering less dependence on mechanical ventilation, thereby potentially reducing ventilator-induced injury. However, the lack of rigorous clinical data has prevented ECMO from becoming the standard of care in the management of ARDS. Therefore, the results of two large ongoing randomized trials, which will hopefully throw more light on the role of ECMO in the management of this disease entity, are keenly awaited. In this article we will provide a basic overview of the development of ECMO, the types of ECMO, the pathogenesis of ARDS, different ventilation strategies for ARDS, the role of ECMO in ARDS and the role of ECMO as a bridge to lung transplantation. PMID- 26848885 TI - Chemoradiotherapy of locally advanced nonsmall cell lung cancer: state of the art and perspectives. AB - PURPOSE OF REVIEW: The treatment of locally advanced nonsmall cell lung cancer (NSCLC) is becoming a significant challenge because of a growing proportion of patients with unresectable or potentially eligible for surgery after a multimodality treatment, stage II to III disease. Despite a multimodality approach consisting in concurrent chemoradiotherapy, the prognosis remains poor. RECENT FINDINGS: Different strategies, including induction and consolidation chemotherapy, chemotherapy regimens, fractionation and radiation doses have been evaluated in phase II and III trials, as well as new therapeutic approaches such as immunotherapy. For patients with resectable stage III disease the optimal strategy remains unclear. The American Society for Radiation and Clinical Oncology and the European Society for Medical Oncology published recent guidelines in 2015. SUMMARY: Concurrent chemoradiotherapy improves overall survival compared with sequential chemotherapy followed by radiation. Adding induction or consolidation chemotherapy to chemoradiotherapy does not appear to improve the outcome. Chemotherapy based on cisplatin combined with radiation is recommended in stage III NSCLC. The standard dose and fractionation of radiotherapy are 60 Gy, one daily fraction of 2 Gy over 6 weeks. Targeted therapies and immunotherapy may improve the management of locally advanced NSCLC in the future. PMID- 26848886 TI - Influence of Solution Composition on the Formation of Surface Nanodroplets by Solvent Exchange. AB - Solvent exchange is a simple process of forming surface nanodroplets on an immersed substrate. In this process, the droplets nucleate and grow in response to transient oversaturation when a good solvent of the droplet liquid is displaced by a poor solvent. Here we will show how the final droplet size is influenced by solution composition in the solvent exchange. To do this, we produced water droplets on a hydrophilic substrate and cyclohexane droplets on a hydrophobic substrate by using a tertiary system of cyclohexane, ethanol, and water. The composition of the good solvent was varied systematically in the one phase region on the phase diagram. We found that the key feature closely related to the droplet size is the area (A) in the phase diagram defined by the phase boundary and the concentration ratio between the good solvent and the droplet liquid. This area reflects the excessive amount of droplet liquid in the tertiary mixture, which can be complicated by bulk droplet formation during solvent exchange. We will also show that the droplet volume per unit surface area also increases with A. The findings from this work will provide guideline for the selection of solution conditions to achieve a desirable droplet size and number density on the surface. PMID- 26848887 TI - Influence of immediate/delayed implant placement and implant platform on the peri implant bone formation. AB - AIM: To determinate the influence of the timing and position of the implant placement, as well as the presence and absence of a buccal gap, associated with different implant platforms on bone formation around implants. METHODS AND MATERIALS: In a first surgical stage, two premolars in one side of the mandibular arch of 07 mongrel dogs were extracted. After a 120-day healing period, a second stage surgery was performed, in which a full flap was raised and two implants were installed. At this same stage, two contralateral premolars were extracted and two immediate implants were placed into the fresh sockets, through the "palatal approach technique" without flap elevation, totaling four implants per animal. The 28 installed implants constituted groups according to the timing (Immediate or delayed) of placement and the type of surface treatment. After 4 months, samples were collected and histomorphometric analysis was performed to determinate buccal surface BIC, lingual surface BIC, total BIC, buccal area, and lingual area of all implants. Kruskal-Wallis and pared Wilcoxon (P < 0.05) tests were performed for statistical analysis. RESULTS: After 4-month healing period, the groups of immediate implants presented better BIC scores, mainly on the buccal surface. Data also suggest better bone area formation around the implants of these same groups. Concerning the type of implant platform, better results were found using Morse taper. CONCLUSION: The flapless technique with "palatal approach," Morse taper implants, and immediate implant placement all have favorable influence on the bone formation around the implants. PMID- 26848888 TI - Multicomponent Fitness Training Improves Walking Economy in Older Adults. AB - BACKGROUND: Walking economy declines with increasing age, possibly leading to mobility limitation in older adults. Multicomponent fitness training could delay the decline in walking economy. PURPOSE: This study aimed to determine the effect of multicomponent fitness training on walking economy in older adults. METHODS: Participants were untrained adults, age 50 to 83 yr (N = 26, 10 males, age = 63 +/- 6 yr, BMI = 25.6 +/- 2.1 kg.m, mean +/- SD). A control group was also recruited (N = 16, 9 males, age = 66 +/- 10 yr, BMI = 25.4 +/- 3.0 kg.m), matching the intervention group for age, weight, body composition, and fitness. The intervention group followed a multicomponent fitness program of 1 h, twice per week during 1 yr. The control group did not take part in any physical training. Fat-free mass, walking economy, and maximal oxygen uptake (VO2max) were measured in both groups before and after the year. Walking economy was measured with indirect calorimetry as the lowest energy needed to displace 1 kg of body mass for 1 m while walking on a treadmill. The data were compared between the two groups with repeated-measures ANOVA. RESULTS: Thirty-two subjects completed all measurements. There was an interaction between the effects of time and group on VO2max (P < 0.05) and walking economy (P < 0.05), whereas fat-free mass did not change significantly (P = 0.06). VO2max decreased by 1.8 mL.kg.min in the control group and increased by 1.3 mL.kg.min in the intervention group. The lowest energy needed to walk increased by 0.12 J.kg.m in the control group and decreased in the intervention group by 0.13 J.kg.m. CONCLUSION: Multicomponent fitness training decreases walking cost in older adults, preserving walking economy. Thus, training programs could delay mobility limitation with increasing age. PMID- 26848889 TI - Association between Objectively Measured Physical Activity and Mortality in NHANES. AB - PURPOSE: We examined total activity, light activity, and moderate-to-vigorous physical activity (MVPA) as predictors of mortality in a nationally representative sample of older adults. Then we explored the theoretical consequences of replacing sedentary time with the same duration of light activity or MVPA. METHODS: Using accelerometer-measured activity, the associations between total activity, light activity (100-2019 counts per minute), and MVPA (>2019 counts per minute) counts and mortality were examined in adults age 50 to 79 yr in the National Health and Nutrition Examination Survey, 2003-2006 (n = 3029), with mortality follow-up through December 2011. Cox proportional hazard models were fitted to estimate mortality risks. An isotemporal substitution model was used to examine the theoretical consequences of replacing sedentary time with light activity or MVPA on mortality. RESULTS: After adjusting for potential confounders, including age, sex, race/ethnicity, education, BMI, and the presence of comorbid conditions, those in the highest tertile of total activity counts had one fifth the risk of death of those in the lowest tertile (hazard ratio [HR] = 0.21, 95% confidence interval [CI] = 0.12-0.38), and those in the middle tertile had one third the risk of death (HR = 0.36, 95% CI = 0.30-0.44). In addition, replacing 30 min of sedentary time with light activity was associated with significant reduction in mortality risk (after 5 yr of follow-up: HR = 0.80, 95% CI = 0.75-0.85). Replacing 30 min of sedentary time with MVPA was also associated with reduction in mortality risk (HR = 0.49, 95% CI = 0.25-0.97). CONCLUSIONS: Greater total activity is associated with lower all-cause mortality risk. Replacing sedentary time with light activity or MVPA may reduce mortality risk for older adults. PMID- 26848891 TI - Gauging the Performance of Density Functionals for Lanthanide-Containing Molecules. AB - Several density functional approaches have been considered for their ability to predict enthalpies of formation and bond dissociation energies for lanthanide containing molecules. To enable comparison with experiment, the Ln54 set, introduced here, is compiled to include lanthanides both in the common 3+ oxidation state as well as in more exotic oxidation states. Due to the magnitude of the experimental uncertainties a "lanthanide chemical accuracy" of 5.0 kcal mol(-1) is proposed. The density functionals considered span the full range of complexity from LDA through double hybrids. The performance of the density functionals is assessed for each class of lanthanide-containing molecules and for the Ln54 molecule set overall. In general, hybrid functionals perform worse than functionals without exact exchange, and TPSS performs the best overall for the Ln54 set with a MAD of 19.2 kcal mol(-1) and MSD of -1.9 kcal mol(-1). PMID- 26848892 TI - Newsletter: President's Message. PMID- 26848893 TI - What Is Happening With Author Comportment? PMID- 26848894 TI - OMAN: The Emergence of the Clinical Nurse Specialist. PMID- 26848895 TI - Improving Literature Searches. PMID- 26848890 TI - Genetic Variant in ACVR2B Is Associated with Lean Mass. AB - INTRODUCTION: Low lean mass (LM) is a risk factor for chronic disease, a major cause of disability and diminished quality of life, and is a heritable trait. However, relatively few specific genetic factors have been identified as potentially influencing this trait. METHODS: In this study, we selected 1493 single-nucleotide polymorphisms (SNP) in 155 candidate genes involved in anabolic, catabolic, growth hormone, and other related pathways and examined their association with LM, assessed by dual-energy x-ray absorptiometry, in a sample of 2760 non-Hispanic and Hispanic white postmenopausal women from the Women's Health Initiative (WHI) Observational Study. We assessed the replication of our top findings in a meta-analysis of 20 genome-wide association studies (n = 38,292) conducted by the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium Musculoskeletal Working Group. RESULTS: We identified 32 SNPs that had nominally significant associations with LM in the WHI cohort. In the replication stage, we find that SNP rs2276541 in the activin A receptor, type IIB (ACVR2B), was significantly associated with LM (beta = 0.15, P = 2.17 * 10). ACVR2B codes for a receptor for a negative regulator of skeletal muscle, myostatin, and has previously been identified in a candidate gene study as a determinant of skeletal muscle mass. CONCLUSIONS: Our findings support a previously proposed role of ACVR2B allelic variation as a determinant of muscle mass and extend prior findings in men and women. Additional large-scale studies will be needed to confirm our findings in different populations. PMID- 26848896 TI - The Antidote Is Finally Here! Idarucizumab, A Specific Reversal Agent for the Anticoagulant Effects of Dabigatran. PMID- 26848897 TI - Surfactant Therapy for Bronchiolitis in Critically Ill Infants. PMID- 26848898 TI - Nurses in Business: The Time Is Now. PMID- 26848899 TI - Structural and Process Factors That Influence Clinical Nurse Specialist Role Implementation. AB - PURPOSE/OBJECTIVES: The aim of this study was to examine the influence of structure and process on clinical nurse specialist (CNS) role implementation. DESIGN: We conducted a secondary analysis of cross-sectional survey data. SETTING: The study was performed in Canada. SAMPLE: The authors included 445 of 471 questionnaires (94.5%) of graduate-prepared CNSs. METHODS: Based on Donabedian's framework, we conducted a secondary analysis of CNS responses using hierarchical regression. The internal consistency of the 6 CNS role dimensions and team dynamics subscales was excellent. RESULTS: The use of a framework to guide CNS role implementation influences all the role dimensions. Employer understanding of the CNS role, working in an urban catchment area, specialty certification, and more years in a CNS role had a direct positive influence on team dynamics. Full-time employment exerted a direct negative influence on this dimension. Furthermore, team dynamics (as a mediator variable), seeing patients in practice, and having an office in the clinical unit exerted a direct positive influence on the clinical dimension. Having an annual performance appraisal and a job description exerted a direct negative influence on the clinical dimension. Employer understanding, working in an urban area, full-time employment, and specialty certification had an indirect effect on the clinical dimension. Accountability to a nonnurse manager exerted a direct negative influence on the education dimension. The research and scholarly/professional development dimensions were influenced by more years in a CNS role. Accountability to a nurse manager exerted a direct positive influence on the organizational leadership dimension; unionization and seeing patients in practice had a direct negative influence on this dimension. Seeing patients in practice and full-time employment exerted a direct positive influence on the consultation dimension. IMPLICATIONS: The identification of structures and processes that influence CNS role implementation may inform strategies used by providers and decision makers to optimize these roles across healthcare settings and support the delivery of high quality care. PMID- 26848900 TI - Evaluation of a Surgical Site Discharge Teaching Tool Using Pictures and a Mirror. AB - PURPOSE: The purpose of this project was to develop, implement, and evaluate a teaching tool for self-assessment of surgical incisions after laparotomy surgery. BACKGROUND: Hospitalized patients have an increased level of acuity and are discharged earlier. Shorter length of stay limits the nurses' ability to provide comprehensive discharge instructions and validate understanding of surgical incision care. DESCRIPTION: Two sets of discharge instructions, 1 with text only and 1 with text and pictures plus a mirror, were provided to patients after laparotomy surgery. A total of 60 patients were recruited over a 3-month period. The first 30 patients received standard discharge instructions (text only). The next 30 patients received discharge instructions using the new program and a handheld mirror to assist with visualization of the incision. A follow-up telephone questionnaire was completed on day 7 after surgery to assess patients' ability to inspect their incision for infection and determine comprehension with discharge instructions. OUTCOME: Patients receiving the revised program had improvement in comprehension of instructions, felt that instructions were clearly stated, and were confident in their ability to identify normal healing versus a surgical site infection (SSI) and about notifying physicians. Compared with the text-only group, the text, picture, and mirror group using the teaching program (text, pictures, and mirror) felt more confident on self-assessment to identify SSI. CONCLUSION: The revised teaching program (text and pictures) and use of a handheld mirror improved patient confidence in self-assessing an incision and increased ease in detecting an SSI. IMPLICATIONS: Clinical nurse specialists can influence patient outcomes. Discharge instructions that include text and pictures plus a mirror should be part of a comprehensive packet for patients asked to assess an incision. PMID- 26848901 TI - Color-Coded Labels Cued Nurses to Adhere to Central Line Connector Change. AB - PURPOSE: This study examined nurses' adherence to policies regarding needleless connector changes using a novel, day-of-the-week, color-coded label compared with usual care that relied on electronic medical record (EMR) documentation. DESIGN: This was a prospective, comparative study. SETTING: The study was performed on 4 medical-surgical units in a seasonally fluctuating, 715-bed healthcare system composed of 2 community hospitals. SAMPLE: Convenience sample was composed of adults with central lines hospitalized for 4 or more days. METHODS: At 4-day intervals, investigators observed bedside label use and EMR needleless connector change documentation. Control patients received standard care-needleless connector change with associated documentation in the EMR. Intervention patients, in addition to standard care, had a day-of-the-week, color-coded label placed on each needleless connector. To account for clustering within unit, multinomial logistic regression models using survey sampling methodology were used to conduct Wald chi tests. A multinominal odds ratio and 95% confidence interval (CI) provided an estimate of using labels that were provided on units relative to usual care documentation of needleless connector change in the EMR. RESULTS: In 335 central line observations, the units with labels (n = 205) had a 321% increase rate of documentation of needleless connector change in the EMR (odds ratio, 4.21; 95% CI, 1.76-10.10; P = .003) compared with the usual care control patients. For units with labels, when labels were present, placement of labels on needleless connectors increased the odds that nurses documented connector changes per policy (4.72; 95% CI, 2.02, 10.98; P = .003). CONCLUSIONS: Day-of-the-week, color-coded labels cued nurses to document central line needleless connector change in the EMR, which increased adherence to the needleless connector change policy. IMPLICATIONS: Providing day-of-the-week, color-coded needleless connector labels increased EMR documentation of timely needleless connector changes. Timely needleless connector changes may lower the incidence of central line-associated bloodstream infection. PMID- 26848902 TI - A Clinical Nurse Specialist-Led Interprofessional Quality Improvement Project to Reduce Hospital-Acquired Pressure Ulcers. AB - PURPOSE: The purpose of this clinical nurse specialist-led interprofessional quality improvement project was to reduce hospital-acquired pressure ulcers (HAPUs) using evidence-based practice. BACKGROUND: Hospital-acquired pressure ulcers (PUs) have been linked to morbidity, poor quality of life, and increasing costs. Pressure ulcer prevention and management remain a challenge for interprofessional teams in acute care settings. RATIONALE: Hospital-acquired PU rate is a critical nursing quality indicator for healthcare organizations and ties directly with Mount Sinai Hospital's (MSH's) mission and vision, which mandates providing the highest quality care to patients and families. DESCRIPTION: This quality improvement project, guided by the Donabedian model, was based on the Registered Nurses' Association of Ontario Best Practice Guideline Risk Assessment & Prevention of Pressure Ulcers. A working group was established to promote evidence-based practice for PU prevention. Initiatives such as documentation standardization, development of staff education and patient and family educational resources, initiation of a hospital-wide inventory for support surfaces, and procurement of equipment were implemented to improve PU prevention and management across the organization. OUTCOME: An 80% decrease in HAPUs has been achieved since the implementation of best practices by the Best Practice Guideline Pressure Ulcer working group. CONCLUSION: The implementation of PU prevention strategies led to a reduction in HAPU rates. The working group will continue to work on building interprofessional awareness and collaboration in order to prevent HAPUs and promote an organizational culture that supports staff development, teamwork and communication. IMPLICATIONS: This quality improvement project is a successful example of an interprofessional clinical nurse specialist-led initiative that impacts patient/family and organization outcomes through the identification and implementation of evidence-based nursing practice. PMID- 26848903 TI - A Journey to Improved Inpatient Glycemic Control by Redesigning Meal Delivery and Insulin Administration. AB - PURPOSE: The purpose of this quality improvement project was to redesign a hospital meal delivery process in order to shorten the time between blood glucose monitoring and corresponding insulin administration and improve glycemic control. DESCRIPTION: This process change redesigned the workflow of the dietary and nursing departments. Modifications included nursing, rather than dietary, delivering meal trays to patients receiving insulin. Dietary marked the appropriate meal trays and phoned each unit prior to arrival on the unit. The process change was trialed on 2 acute care units prior to implementation hospital wide. Elapsed time between blood glucose monitoring and insulin administration was analyzed before and after process change as well as evaluation of glucometrics: percentage of patients with blood glucose between 70 and 180 mg/dL (percent perfect), blood glucose greater than 300 mg/dL (extreme hyperglycemia), and blood glucose less than 70 mg/dL (hypoglycemia). RESULTS: Percent perfect glucose results improved from 45% to 53%, extreme hyperglycemia (blood glucose >300 mg/dL) fell from 11.7% to 5%. Hypoglycemia demonstrated a downward trend line, demonstrating that with improving glycemic control hypoglycemia rates did not increase. Percentage of patients receiving meal insulin within 30 minutes of blood glucose check increased from 35% to 73%. CONCLUSION: In the hospital, numerous obstacles were present that interfered with on-time meal insulin delivery. Establishing a meal delivery process with the nurse performing the premeal blood glucose check, delivering the meal, and administering the insulin improves overall blood glucose control. IMPLICATIONS: Nurse-led process improvement of blood glucose monitoring, meal tray delivery, and insulin administration does lead to improved glycemic control for the inpatient population. PMID- 26848904 TI - Perspectives on Global Healthcare. PMID- 26848905 TI - Greg Lum's "Prisoner of Pain". PMID- 26848906 TI - A Comparison of Personal Protective Standards: Caring for Patients With Ebola Virus. AB - PURPOSE: The purpose of this article is to discuss the variance in requirements for personal protective equipment (PPE) used among healthcare workers to treat patients actively infected with the Ebola virus in West Africa. BACKGROUND: The Ebola virus is a highly contagious disease, which has killed 11020 people within the past year. In order to combat the disease and treat those with active infections, healthcare workers are required to use PPE. The guidelines for the PPE, in addition to the requirements of what should be worn, are varied between the World Health Organization (WHO) and the Centers for Disease Control and Prevention. DESCRIPTION: A military unit was composed of sister services (Army, Navy, and Air Force) deployed to Monrovia, Liberia, to assist in mitigating the devastating effects of the Ebola virus. Each service member was taught PPE standards according to the WHO and were assigned to teach healthcare workers from around the world on how to manage the care of patients infected with the Ebola virus, while simultaneously taking diligent precautions to protect themselves against the deadly disease. OUTCOME: More than 1500 healthcare workers were instructed on the latest PPE standards before they entered into the Ebola treatment units (ETUs) that were being constructed in Liberia. Cumulative death rates from the Ebola virus in Liberia increased from 2413 in October 2014 to 3686 by January 2015. CONCLUSION/IMPLICATIONS FOR PRACTICE: The rapid decline in Ebola mortality is multifactorial. The efforts of US military medical personnel likely were a contributing factor in this rapid decline as those international health workers were afforded the latest in PPE training with strict attention to detail. US military medical personnel, in concert with other governmental agencies, created a potent force multiplier in the efforts to curb this deadly infection. The educational initiative was essential to the slowdown in the spread of the Ebola virus in Liberia. Recommendations for a detailed review of the PPE standards and variances in practice from both WHO and Centers for Disease Control and Prevention are necessary to standardize processes across international healthcare workers to expedite the care for future infectious disease outbreaks. A possible solution is to modify the PPE process to standardize with the WHO guidelines. Key stakeholders from all levels (staff nurse, clinical nurse specialist, nurse managers, infectious disease experts, etc) need to be heavily involved in this process. PMID- 26848908 TI - Radical treatment for bilateral vertebral artery dissecting aneurysms by reconstruction of the vertebral artery. AB - OBJECTIVE Bilateral vertebral artery dissecting aneurysms (VADAs) have a poor prognosis because progressive enlargement of the aneurysms compresses the brainstem or causes subarachnoid hemorrhage. The trapping of 1 vertebral artery (VA) places increased hemodynamic stress on the contralateral VA and may lead to enlargement and rupture. Therefore, management strategies are controversial. This study describes a radical treatment for bilateral VADAs using bypass surgery. METHODS Seven patients with bilateral VADAs were included. Three patients were treated by trapping of 1 VA via coiling or clipping at another hospital; the previously treated VA in 1 patient and the contralateral untreated VA in 2 patients subsequently enlarged. The other 4 patients presented without previous intervention and progressive enlargement of the aneurysms. RESULTS The post-coil embolization patients underwent V3-posterior cerebral artery (PCA) bypass and trapping. The other 4 patients underwent VA reconstruction via V3-V4 or V4-V4 bypass, with contralateral trapping on a separate day in 3 patients and observation in 1 patient. Perioperative complications included 1 case of cerebrospinal fluid leakage for which the patient required an additional operation, 1 case of dysphagia and facial palsy due to sigmoid sinus thrombosis, and 1 case of dysphagia. The long-term outcomes of these patients were favorable. CONCLUSIONS Patients with bilateral VADAs require treatment on both sides. If VA trapping is performed first, the treatment options for the other side are limited to V3-PCA bypass and trapping. This procedure is effective; however, it is also invasive and technically difficult. In cases of bilateral VADAs in which it is feasible to reconstruct 1 side, the best approach is to begin by reconstructing the VA that appears technically easiest, followed by trapping of the contralateral VADA. This strategy allows enough time to suture vessels because contralateral reverse flow is maintained. PMID- 26848910 TI - Letter to the Editor: Pituitary tumors and cavernous sinus extension. PMID- 26848909 TI - Brain tissue oxygen tension and its response to physiological manipulations: influence of distance from injury site in a swine model of traumatic brain injury. AB - OBJECTIVE The optimal site for placement of tissue oxygen probes following traumatic brain injury (TBI) remains unresolved. The authors used a previously described swine model of focal TBI and studied brain tissue oxygen tension (PbtO2) at the sites of contusion, proximal and distal to contusion, and in the contralateral hemisphere to determine the effect of probe location on PbtO2 and to assess the effects of physiological interventions on PbtO2 at these different sites. METHODS A controlled cortical impact device was used to generate a focal lesion in the right frontal lobe in 12 anesthetized swine. PbtO2 was measured using Licox brain tissue oxygen probes placed at the site of contusion, in pericontusional tissue (proximal probe), in the right parietal region (distal probe), and in the contralateral hemisphere. PbtO2 was measured during normoxia, hyperoxia, hypoventilation, and hyperventilation. RESULTS Physiological interventions led to expected changes, including a large increase in partial pressure of oxygen in arterial blood with hyperoxia, increased intracranial pressure (ICP) with hypoventilation, and decreased ICP with hyperventilation. Importantly, PbtO2 decreased substantially with proximity to the focal injury (contusion and proximal probes), and this difference was maintained at different levels of fraction of inspired oxygen and partial pressure of carbon dioxide in arterial blood. In the distal and contralateral probes, hypoventilation and hyperventilation were associated with expected increased and decreased PbtO2 values, respectively. However, in the contusion and proximal probes, these effects were diminished, consistent with loss of cerebrovascular CO2 reactivity at and near the injury site. Similarly, hyperoxia led to the expected rise in PbtO2 only in the distal and contralateral probes, with little or no effect in the proximal and contusion probes, respectively. CONCLUSIONS PbtO2 measurements are strongly influenced by the distance from the site of focal injury. Physiological alterations, including hyperoxia, hyperventilation, and hypoventilation substantially affect PbtO2 values distal to the site of injury but have little effect in and around the site of contusion. Clinical interpretations of brain tissue oxygen measurements should take into account the spatial relation of probe position to the site of injury. The decision of where to place a brain tissue oxygen probe in TBI patients should also take these factors into consideration. PMID- 26848911 TI - Convection-enhanced delivery improves MRI visualization of basal ganglia for stereotactic surgery. AB - OBJECTIVE Stereotactic deep brain stimulation surgery is most commonly performed while patients are awake. This allows for intraoperative clinical assessment and electrophysiological target verification, thereby promoting favorable outcomes with few side effects. Intraoperative CT and MRI have challenged this concept of clinical treatment validation. Image-guided surgery is capable of delivering electrodes precisely to a planned, stereotactic target; however, these methods can be limited by low anatomical resolution even with sophisticated MRI modalities. The authors are developing a novel method using convection-enhanced delivery to safely manipulate the extracellular space surrounding common anatomical targets for surgery. By altering the extracellular content of deep subcortical structures and their associated white matter tracts, the MRI visualization of the basal ganglia can be improved to better define the anatomy. This technique could greatly improve the accuracy and success of stereotactic surgery, potentially eliminating the reliance on awake surgery. METHODS Observations were made in the clinical setting where vasogenic and cytotoxic edema improved the MRI visualization of the basal ganglia. These findings were replicated in the experimental setting using an FDA-approved intracerebral catheter that was stereotactically inserted into the thalamus or basal ganglia of 7 swine. Five swine were infused with normal saline, and 2 were infused with autologous CSF. Flow rates varied between 1 MUl/min to 6 MUl/min to achieve convective distributions. Concurrent MRI was performed at 15-minute intervals to monitor the volume of infusion and observe the imaging changes of the deep subcortical structures. The animals were then clinically observed, and necropsy was performed within 48 hours, 1 week, or 1 month for histological analysis. RESULTS In all animals, the white matter tracts became hyperintense on T2 weighted imaging as compared with basal ganglia nuclei, enabling better definition of the deep brain anatomy. The volume of distribution and infusion (Vd/Vi ratio) ranged from 2.5 to 4.5. There were no observed clinical effects from the infusions. Histological analysis demonstrated mild neuronal effects from saline infusions but no effects from CSF infusions. CONCLUSIONS This work provides the initial foundation for a novel approach to improve the visualization of deep brain anatomy during MRI-guided, stereotactic procedures. Convective infusions of CSF alter the extracellular fluid content of the brain for improved MRI without evidence of clinical or toxic effects. PMID- 26848912 TI - Brain mapping: a novel intraoperative neuropsychological approach. AB - OBJECTIVE Awake surgery and mapping are performed in patients with low-grade tumors infiltrating functional brain areas for which the greater the resection, the longer the patient survival. However, the extent of resection is subject to preservation of cognitive functions, and in the absence of proper feedback during mapping, the surgeon may be less prone to perform an extensive resection. The object of this study was to perform real-time continuous assessment of cognitive function during the resection of tumor tissue that could infiltrate eloquent tissue. METHODS The authors evaluated the use of new, complex real-time neuropsychological testing (RTNT) in a series of 92 patients. They reported normal scoring and decrements in patient performance as well as reversible intraoperative neuropsychological dysfunctions in tasks (for example, naming) associated with different cognitive abilities. RESULTS RTNT allowed one to obtain a more defined neuropsychological picture of the impact of surgery. The influence of this monitoring on surgical strategy was expressed as the mean extent of resection: 95% (range 73%-100%). At 1 week postsurgery, the neuropsychological scores were very similar to those detected with RTNT, revealing the validity of the RTNT technique as a predictive tool. At the follow-up, the majority of neuropsychological scores were still > 70%, indicating a decrease of < 30%. CONCLUSIONS RTNT enables continuous enriched intraoperative feedback, allowing the surgeon to increase the extent of resection. In sharp contrast to classic mapping techniques, RTNT allows testing of several cognitive functions for one brain area under surgery. PMID- 26848913 TI - Diffusion tensor imaging assessment of microstructural brainstem integrity in Chiari malformation Type I. AB - OBJECTIVE The diagnosis of Chiari malformation Type I (CM-I) is primarily based on the degree of cerebellar tonsillar herniation even though it does not always correlate with symptoms. Neurological dysfunction in CM-I presumably results from brainstem compression. With the premise that conventional MRI does not reveal brain microstructural changes, this study examined both structural and microstructural neuroimaging metrics to distinguish patients with CM-I from age- and sex-matched healthy control subjects. METHODS Eight patients with CM-I and 16 controls were analyzed. Image postprocessing involved coregistration of anatomical T1-weighted with diffusion tensor images using 3D Slicer software. The structural parameters included volumes of the posterior fossa, fourth ventricle, and tentorial angle. Fractional anisotropy (FA) was calculated separately in the anterior and posterior compartments of the lower brainstem. RESULTS The mean age of patients in the CM-I cohort was 42.6 +/- 10.4 years with mean tonsillar herniation of 12 mm (SD 0.7 mm). There were no significant differences in the posterior fossa volume (p = 0.06) or fourth ventricular volume between the 2 groups (p = 0.11). However, the FA in the anterior brainstem compartment was significantly higher in patients with CM-I preoperatively (p = 0.001). The FA values normalized after Chiari decompression except for persistently elevated FA in the posterior brainstem compartment in patients with CM-I and syrinx. CONCLUSIONS In this case-control study, microstructural alterations appear to be reliably associated with the diagnosis of CM-I, with a significantly elevated FA in the lower brainstem in patients with CM-I compared with controls. More importantly, the FA values normalized after decompressive surgery. These findings should be validated in future studies to determine the significance of diffusion tensor imaging-based assessment of brainstem microstructural integrity as an adjunct to the clinical assessment in patients with CM-I. PMID- 26848915 TI - Letter to the Editor: Failing our colleagues, are we supporting our cerebrovascular partners? PMID- 26848914 TI - Unilateral vestibular schwannoma in a patient with schwannomatosis in the absence of LZTR1 mutation. AB - The presence of vestibular schwannomas has long been considered an exclusion criterion for the diagnosis of schwannomatosis. Recently, 2 cases of vestibular schwannoma were reported in patients with schwannomatosis, leading to a revision of the diagnostic criteria for this genetic disorder. Overall, the relative infrequency of vestibular schwannomas in schwannomatosis is unexplained, and the genetics of this uncommon phenomenon have not been described. The authors report on a family with clinical manifestations consistent with schwannomatosis, including 4 affected members, that was identified as having an affected member harboring a unilateral cerebellopontine angle mass with extension into the internal auditory canal. Radiologically, this mass was consistent with a vestibular schwannoma and resulted in a symptomatic change in ipsilateral hearing (word recognition 86% at 52 dB) and increased latency of the wave I-V interval on auditory brainstem response testing. The patient was found to be negative for a germline mutation of NF2 and LZTR1, and her affected mother was found to harbor neither NF2 nor SMARCB1 mutations on genetic testing. Although vestibular schwannomas have been classically considered to not occur in the setting of schwannomatosis, this patient with schwannomatosis and a vestibular schwannoma further confirms that schwannomas can occur on the vestibular nerve in this syndrome. Further, this is the first such case found to be negative for a mutation on the LZTR1 gene. PMID- 26848916 TI - Comparative analysis of the anterior transpetrosal approach with the endoscopic endonasal approach to the petroclival region. AB - OBJECTIVE The endoscopic endonasal approach (EEA) offers direct access to midline skull base lesions, and the anterior transpetrosal approach (ATPA) stands out as a method for granting entry into the upper and middle clival areas. This study evaluated the feasibility of performing EEA for tumors located in the petroclival region in comparison with ATPA. METHODS On 8 embalmed cadaver heads, EEA to the petroclival region was performed utilizing a 4-mm endoscope with either 0 degrees or 30 degrees lenses, and an ATPA was performed under microscopic visualization. A comparison was executed based on measurements of 5 heads (10 sides). Case illustrations were utilized to demonstrate the advantages and disadvantages of EEA and ATPA when dealing with petroclival conditions. RESULTS Extradurally, EEA allows direct access to the medial petrous apex, which is limited by the petrous and paraclival internal carotid artery (ICA) segments laterally. The ATPA offers direct access to the petrous apex, which is blocked by the petrous ICA and abducens nerve inferiorly. Intradurally, the EEA allows a direct view of the areas medial to the cisternal segment of cranial nerve VI with limited lateral exposure. ATPA offers excellent access to the cistern between cranial nerves III and VIII. The quantitative analysis demonstrated that the EEA corridor could be expanded laterally with an angled drill up to 1.8 times wider than the bone window between both paraclival ICA segments. CONCLUSIONS The midline, horizontal line of the petrous ICA segment, paraclival ICA segment, and the abducens nerve are the main landmarks used to decide which approach to the petroclival region to select. The EEA is superior to the ATPA for accessing lesions medial or caudal to the abducens nerve, such as chordomas, chondrosarcomas, and midclival meningiomas. The ATPA is superior to lesions located posterior and/or lateral to the paraclival ICA segment and lesions with extension to the middle fossa and/or infratemporal fossa. The EEA and ATPA are complementary and can be used independently or in combination with each other in order to approach complex petroclival lesions. PMID- 26848917 TI - Intraoperative premature rupture of middle cerebral artery aneurysms: risk factors and sphenoid ridge proximation sign. AB - OBJECTIVE This study was an investigation of surgical cases of a ruptured middle cerebral artery (MCA) aneurysm that was conducted to identify the risk factors of an intraoperative premature rupture. METHODS Among 927 patients with a ruptured intracranial aneurysm who were treated over an 8-year period, the medical records of 182 consecutive patients with a ruptured MCA aneurysm were examined for cases of a premature rupture, and the risk factors were then investigated. The risk factors considered for an intraoperative premature rupture of an MCA aneurysm included the following: patient age; sex; World Federation of Neurosurgical Societies clinical grade; modified Fisher grade; presence of an intracerebral hemorrhage (ICH); location of the ICH (frontal or temporal); volume of the ICH; maximum diameter of the ruptured MCA aneurysm; length of the preaneurysmal M1 segment between the carotid bifurcation and the MCA aneurysm; and a sign of sphenoid ridge proximation. The sphenoid ridge proximation sign was defined as a spatial proximation < 4 mm between the sphenoid ridge and the rupture point of the MCA aneurysm, such as a daughter sac, irregularity, or dome of the aneurysm, based on the axial source images of the brain CT angiography sequences. RESULTS A total of 11 patients (6.0%) suffered a premature rupture of the MCA aneurysm during surgery. The premature rupture occurrences were classified according to the stage of the surgery, as follows: 1) craniotomy and dural opening (n = 1); 2) aspiration or removal of the ICH (n = 1); 3) retraction of the frontal lobe (n = 1); 4) dissection of the sphenoid segment of the sylvian fissure to access the proximal vessel (n = 4); and 5) perianeurysmal dissection (n = 4). The multivariate analysis with a binary logistic regression revealed that presence of a sphenoid ridge proximation sign (p < 0.001), presence of a frontal ICH associated with the ruptured MCA aneurysm (p = 0.019), and a short preaneurysmal M1 segment (p = 0.043) were all statistically significant risk factors for a premature rupture. Plus, a receiver operating characteristic curve analysis revealed that a preaneurysmal M1 segment length <= 13.3 mm was the best cutoff value for predicting the occurrence of a premature rupture (area under curve 0.747; sensitivity 63.64%; specificity 81.66%). CONCLUSIONS Patients exhibiting a sphenoid ridge proximation sign, the presence of a frontal ICH, and/or a short preaneurysmal M1 segment are at high risk for an intraoperative premature rupture of a MCA aneurysm. Such high-risk MCA aneurysms have a superficial location close to the arachnoid in the sphenoidal compartment of the sylvian fissure and have a rupture point directed anteriorly. PMID- 26848918 TI - Letter to the Editor: The endoscopic endonasal approach in the treatment of olfactory groove meningiomas. PMID- 26848919 TI - Nonthermal ablation in the rat brain using focused ultrasound and an ultrasound contrast agent: long-term effects. AB - OBJECTIVE Thermal ablation with transcranial MRI-guided focused ultrasound (FUS) is currently under investigation as a less invasive alternative to radiosurgery and resection. A major limitation of the method is that its use is currently restricted to centrally located brain targets. The combination of FUS and a microbubble-based ultrasound contrast agent greatly reduces the ultrasound exposure level needed to ablate brain tissue and could be an effective means to increase the "treatment envelope" for FUS in the brain. This method, however, ablates tissue through a different mechanism: destruction of the microvasculature. It is not known whether nonthermal FUS ablation in substantial volumes of tissue can safely be performed without unexpected effects. The authors investigated this question by ablating volumes in the brains of normal rats. METHODS Overlapping sonications were performed in rats (n = 15) to ablate a volume in 1 hemisphere per animal. The sonications (10-msec bursts at 1 Hz for 60 seconds; peak negative pressure 0.8 MPa) were combined with the ultrasound contrast agent Optison (100 ul/kg). The rats were followed with MRI for 4-9 weeks after FUS, and the brains were examined with histological methods. RESULTS Two weeks after sonication and later, the lesions appeared as cyst-like areas in T2 weighted MR images that were stable over time. Histological examination demonstrated well-defined lesions consisting of a cyst-like cavity that remained lined by astrocytic tissue. Some white matter structures within the sonicated area were partially intact. CONCLUSIONS The results of this study indicate that nonthermal FUS ablation can be used to safely ablate tissue volumes in the brain without unexpected delayed effects. The findings are encouraging for the use of this ablation method in the brain. PMID- 26848921 TI - Visualization of lenticulostriate arteries during insular low-grade glioma surgeries by navigated 3D ultrasound power Doppler: technical note. AB - OBJECTIVE Resection of insular gliomas is challenging. In cases of intraoperative injury to the lenticulostriate arteries (LSAs), the usual result is a dense hemiplegia. LSAs are usually localized just behind the medial tumor border but they can also be encased by the tumor. Thus, exact localization of these perforators is important. However, intraoperative localization of LSAs using conventional neuronavigation can be difficult due to brain shift. In this paper, the authors present a novel method of intraoperative LSA visualization by navigated 3D ultrasound (3DUS) power Doppler. This technique enables almost real time imaging of LSAs and evaluation of their shift during insular tumor resections. METHODS Six patients harboring insular Grade II gliomas were consecutively operated on at the Department of Neurosurgery in Bratislava using visualization of LSAs by navigated 3DUS power Doppler. In all cases, the 3DUS data were repeatedly updated to compensate for the brain shift and display the actual position of LSAs and residual tumor. RESULTS Successful visualization of LSAs was achieved in all cases. During all surgeries, the distance between the bottom of the resection cavity and LSAs could be accurately evaluated; in all tumors the resection approached the LSAs and only a minimal amount of tissue covering these perforators was intentionally left in place to avoid injury to them. CONCLUSIONS Visualization of LSAs by navigated 3DUS power Doppler is a useful tool that may help to prevent injury of LSAs during removal of insular low grade gliomas. However, reliability of this method has to be carefully evaluated in further studies. PMID- 26848920 TI - Correlation of personality assessments with standard selection criteria for neurosurgical residency applicants. AB - OBJECTIVE Neurosurgery is among the most competitive residencies, as evidenced by the high number of applicants for relatively few positions. Although it is important to recruit candidates who have the intellectual capacity and drive to succeed, traditional objective selection criteria, such as US Medical Licensing Examination (USMLE) (also known as Step 1) score, number of publications, and class ranking, have not been shown to consistently predict clinical and academic success. Furthermore, these traditional objective parameters have not been associated with specific personality traits. METHODS The authors sought to determine the efficacy of a personality assessment in the selection of neurosurgery residents. Specifically, the aim was to determine the correlation between traditional measures used to evaluate an applicant (e.g., USMLE score, number of publications, MD/PhD status) and corresponding validated personality traits. RESULTS Fifty-four neurosurgery residency applicants were interviewed at the Cleveland Clinic during the 2014-2015 application cycle. No differences in validated personality scores were identified between the 46 MD applicants and 8 MD/PhD applicants. The mean USMLE score (+/- SD) was 252.3 +/- 11.9, and those in the high-USMLE-score category (USMLE score >= 260) had a significantly lower "imaginative" score (a stress measure of eccentric thinking and impatience with those who think more slowly). The average number of publications per applicant was 8.6 +/- 7.9, and there was a significant positive correlation (r = 0.339, p = 0.016) between greater number of publications and a higher "adjustment" score (a measure of being even-tempered, having composure under pressure). Significant negative correlations existed between the total number of publications and the "excitable" score (a measure of being emotionally volatile) (r = -0.299, p = 0.035) as well as the "skeptical" score (measure of being sensitive to criticism) (r = -0.325, p = 0.021). The average medical school rank was 25.8, and medical school rankings were positively correlated with the "imaginative" score (r = 0.287, p = 0.044). CONCLUSIONS This is the first study to investigate the use of personality scores in the selection of neurosurgical residents. The use of personality assessments has the potential to provide insight into an applicant's future behavior as a resident and beyond. This information may be useful in the selection of neurosurgical residents and can be further used to customize the teaching of residents and for enabling them to recognize their own strengths and weaknesses for self-improvement. PMID- 26848922 TI - Stimulation sites in the subthalamic nucleus and clinical improvement in Parkinson's disease: a new approach for active contact localization. AB - OBJECTIVE Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely used in patients with Parkinson's disease (PD). However, which target area of this region results in the highest antiparkinsonian efficacy is still a matter of debate. The aim of this study was to develop a more accurate methodology to locate the electrodes and the contacts used for chronic stimulation (active contacts) in the subthalamic region, and to determine the position at which stimulation conveys the greatest clinical benefit. METHODS The study group comprised 40 patients with PD in whom bilateral DBS electrodes had been implanted in the STN. Based on the Morel atlas, the authors created an adaptable 3D atlas that takes into account individual anatomical variability and divides the STN into functional territories. The locations of the electrodes and active contacts were obtained from an accurate volumetric assessment of the artifact using preoperative and postoperative MR images. Active contacts were positioned in the 3D atlas using stereotactic coordinates and a new volumetric method based on an ellipsoid representation created from all voxels that belong to a set of contacts. The antiparkinsonian benefit of the stimulation was evaluated by the reduction in the Unified Parkinson's Disease Rating Scale Part III (UPDRS-III) score and in the levodopa equivalent daily dose (LEDD) at 6 months. A homogeneous group classification for contact position and the respective clinical improvement was applied using a hierarchical clustering method. RESULTS Subthalamic stimulation induced a significant reduction of 58.0% +/- 16.5% in the UPDRS-III score (p < 0.001) and 64.9% +/- 21.0% in the LEDD (p < 0.001). The greatest reductions in the total and contralateral UPDRS-III scores (64% and 76%, respectively) and in the LEDD (73%) were obtained when the active contacts were placed approximately 12 mm lateral to the midline, with no influence of the position being observed in the anteroposterior and dorsoventral axes. In contrast, contacts located about 10 mm from the midline only reduced the global and contralateral UPDRS-III scores by 47% and 41%, respectively, and the LEDD by 33%. Using the ellipsoid method of location, active contacts with the highest benefit were positioned in the rostral and most lateral portion of the STN and at the interface between this subthalamic region, the zona incerta, and the thalamic fasciculus. Contacts placed in the most medial regions of the motor STN area provided the lowest clinical efficacy. CONCLUSIONS The authors report an accurate new methodology to assess the position of electrodes and contacts used for chronic subthalamic stimulation. Using this approach, the highest antiparkinsonian benefit is achieved when active contacts are located within the rostral and the most lateral parts of the motor region of the STN and at the interface of this region and adjacent areas (zona incerta and thalamic fasciculus). PMID- 26848923 TI - RADICLE Moms study: Minority stress and implications for lesbian mothers. AB - Little is known about depressive symptoms among mothers who identify as lesbian. The aim of the researchers in the Relationships And Depression In Childbearing LEsbian (RADICLE) Moms study was to investigate the minority stress model to determine if higher levels of social support altered the relationship between gay specific minority stress and depressive symptoms in a sample of self-identified lesbian women who had one or more children less than 18 years of age living in the household. The authors hypothesized that social support would influence the relationship between depressive symptoms and minority stress. Participants (n = 131) completed an anonymous Internet survey between May and December, 2011. Controlling for demographic factors and utilizing independent hierarchical multiple regression analyses the authors examined the relationships between depressive symptoms and social support, minority stress, and general stress. While each of these factors had a significantly positive relationship to depressive symptoms, using stepwise regression analyses the authors identified general stress as the most significant factor. Mediation analysis revealed that social support fully mediated the relationship between minority stress and depressive symptoms. This pilot study provides support for development of intervention strategies to decrease general stress and or increase social support among lesbian mothers. PMID- 26848924 TI - Novel Bi12O15Cl6 Photocatalyst for the Degradation of Bisphenol A under Visible Light Irradiation. AB - Bisphenol A (BPA), a typical endocrine-disrupting chemical, is widely present in water environments, and its efficient and cost-effective removal is greatly needed. Among various physicochemical methods for BPA degradation, visible-light driven catalytic degradation of BPA is a promising approach because of its utilization of solar energy. Bismuth oxychloride (BiOCl) is recognized as an efficient photocatalyst, but its band gap, >3.0 eV, makes it inefficient for solar energy utilization, especially for degrading nondye pollutants like BPA. Thus, preparation and application of bismuth oxychloride photocatalysts with an increased visible-light activity are essential. In this work, inspired by density functional theory calculations, a novel bismuth oxychloride photocatalyst, Bi12O15Cl6, was designed. The nanosheets were successfully synthesized using a facile solvothermal method followed by a thermal treatment route. The prepared Bi12O15Cl6 nanosheets had a favorable energy band structure and thus exhibited a superior visible-light photocatalytic activity for degrading BPA. The BPA degradation rate by the Bi12O15Cl6 was determined to be 13.6 and 8.7 times faster than those for BiOCl and TiO2 (P25), respectively. The photogenerated reactive species and degradation intermediates were identified, and the photocatalytic mechanism was elucidated. Furthermore, the as-synthesized Bi12O15Cl6 nanosheets remained stable in the photocatalytic process and could be used repeatedly, demonstrating their promising application in the degradation of diverse pollutants in water and wastewater. PMID- 26848925 TI - Effect of Collateral Sprouting on Donor Nerve Function After Nerve Coaptation: A Study of the Brachial Plexus. AB - BACKGROUND The aim of the present study was to evaluate the donor nerve from the C7 spinal nerve of the rabbit brachial plexus after a coaptation procedure. Assessment was performed of avulsion of the C5 and C6 spinal nerves treated by coaptation of these nerves to the C7 spinal nerve. MATERIAL AND METHODS After nerve injury, fourteen rabbits were treated by end-to-side coaptation (ETS), and fourteen animals were treated by side-to-side coaptation (STS) on the right brachial plexus. Electrophysiological and histomorphometric analyses and the skin pinch test were used to evaluate the outcomes. RESULTS There was no statistically significant difference in the G-ratio proximal and distal to the coaptation in the ETS group, but the differences in the axon, myelin sheath and fiber diameters were statistically significant. The comparison of the ETS and STS groups distal to the coaptation with the controls demonstrated statistically significant differences in the fiber, axon, and myelin sheath diameters. With respect to the G-ratio, the ETS group exhibited no significant differences relative to the control, whereas the G-ratio in the STS group and the controls differed significantly. In the electrophysiological study, the ETS and STS groups exhibited major changes in the biceps and subscapularis muscles. CONCLUSIONS The coaptation procedure affects the histological structure of the nerve donor, but it does not translate into changes in nerve conduction or the sensory function of the limb. The donor nerve lesion in the ETS group is transient and has minimal clinical relevance. PMID- 26848926 TI - Antioxidant treatments for schizophrenia. AB - BACKGROUND: There is accumulating evidence that progressive changes in brain structure and function take place as schizophrenia unfolds. Among many possible candidates, oxidative stress may be one of the mediators of neuroprogression, grey matter loss and subsequent cognitive and functional impairment. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative stress or its consequences. They may act from directly scavenging free radicals to increasing anti-oxidative defences. There is evidence that current treatments impact oxidative pathways and may to some extent reverse pro-oxidative states in schizophrenia. The existing literature, however, indicates that these treatments do not fully restore the deficits in antioxidant levels or restore levels of oxidants in schizophrenia. As such, there has been interest in developing interventions aimed at restoring this oxidative balance beyond the benefits of antipsychotics in this direction. If antioxidants are to have a place in the treatment of this serious condition, the relevant and up-to-date information should be available to clinicians and investigators. OBJECTIVES: To evaluate the effect of antioxidants as add-on treatments to standard antipsychotic medication for improving acute psychotic episodes and core symptoms, and preventing relapse in people with schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials which is based on regular searches of CINAHL, BIOSIS, AMED, Embase, PubMed, MEDLINE, PsycINFO, and registries of clinical trials. There are no language, time, document type, or publication status limitations for inclusion of records in the register. We ran this search in November 2010, and again on 8 January 2015. We also inspected references of all identified studies for further trials and contacted authors of trials for additional information. SELECTION CRITERIA: We included reports if they were randomised controlled trials (RCTs) involving people with schizophrenia who had been allocated to either a substance with antioxidant potential or to a placebo as an adjunct to standard antipsychotic treatment. DATA COLLECTION AND ANALYSIS: We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE. MAIN RESULTS: The review includes 22 RCTs of varying quality and sample size studying Ginkgo biloba, N-acetyl cysteine (NAC), allopurinol, dehydroepiandrosterone (DHEA), vitamin C, vitamin E or selegiline. Median follow up was eight weeks. Only three studies including a minority of the participants reported our a priori selected primary outcome of clinically important response. Short-term data for this outcome (measured as at least 20% improvement in scores on Positive and Negative Syndrome Scale (PANSS)) were similar (3 RCTs, n = 229, RR 0.77, 95% CI 0.53 to 1.12, low quality evidence). Studies usually reported only endpoint psychopathology rating scale scores. Psychotic symptoms were lower in those using an adjunctive antioxidant according to the PANSS ( 7 RCTS, n = 584, MD -6.00, 95% CI -10.35 to -1.65, very low quality evidence) and the Brief Psychiatric Rating Scale (BPRS) (8 RCTS, n = 843, MD -3.20, 95% CI -5.63 to 0.78, low quality evidence). There was no overall short-term difference in leaving the study early (16 RCTs, n = 1584, RR 0.73, 95% CI 0.48 to 1.11, moderate quality evidence), or in general functioning (2 RCTs, n = 52, MD -1.11, 95% CI -8.07 to 5.86, low quality evidence). Adverse events were generally poorly reported. Three studies reported useable data for 'any serious adverse effect', results were equivocal (3 RCTs, n = 234, RR 0.65, 95% CI 0.19 to 2.27, low quality evidence). No evidence was available for relapse, quality of life or service use. AUTHORS' CONCLUSIONS: Although 22 trials could be included in this review, the evidence provided is limited and mostly not relevant to clinicians or consumers. Overall, although there was low risk of attrition and selective data reporting bias within the trials, the trials themselves were not adequately powered and need more substantial follow-up periods. There is a need for larger trials with longer periods of follow-up to be conducted. Outcomes should be meaningful for those with schizophrenia, and include measures of improvement and relapse (not just rating scale scores), functioning and quality of life and acceptability and, importantly, safety data. PMID- 26848927 TI - Comparison of cancer survival trends in the United States of adolescents and young adults with those in children and older adults. AB - BACKGROUND: With prior reports indicating a lack of progress in survival improvement in older adolescents and young adults (AYAs) aged 15 to 39 years with cancer compared with both younger and older patients with cancer, the current analysis provides an update of survival trends of cancers among AYAs, children, and older adults. METHODS: Data from the National Cancer Institute Surveillance, Epidemiology, and End Results database for 13 regions were used to ascertain survival trends of the 34 most frequent cancers diagnosed in AYAs compared with children and older adults. RESULTS: As of 2002 through 2006, the 5-year relative survival rate for all invasive cancers in AYAs was 82.5% (standard error, 0.2%). In AYAs, 14 cancers demonstrated evidence of a statistically significant improvement in their 5-year relative survival since 1992. Survival improved less in AYAs than in children for acute myeloid leukemia and medulloblastoma. Fourteen cancers had survival improvements that were found to be less in AYAs compared with older adults, including hepatic carcinoma, acute myeloid leukemia, high grade astrocytoma, acute lymphocytic leukemia, pancreatic carcinoma, low-grade astrocytoma, gastric carcinoma, renal carcinoma, cancer of the oral cavity and pharynx, Hodgkin lymphoma, ovarian cancer, fibromatous sarcoma, other soft tissue sarcoma, and thyroid carcinoma. CONCLUSIONS: Improvements in the survival of several cancer types that occur frequently in AYAs are encouraging. However, survival does not appear to be improving to the same extent in AYAs as in children or older adults for several cancers. Further investment in exploring the distinct biology of tumors in this age group, and of their hosts, must be a priority in AYA oncology. PMID- 26848930 TI - Where There's Smoke, There's Fire? Significance of Atrial Fibrillation in Young Patients. AB - BACKGROUND: Atrial fibrillation (AF), a disease of the elderly, occasionally occurs at younger age. Pathophysiology of AF in younger patients is diverse, including channelopathies and cardiomyopathies. Data on the significance and complications of AF in young patients are scarce. HYPOTHESIS: Atrial fibrillation is the first manifestation of cardiovascular disease (CVD) in young patients. METHODS: From 11 888 patients in a university hospital database, patients age <=35 years were identified. A composite of stroke/transient ischemic attack, thromboembolic events, major bleeding, and death was the primary endpoint. Stroke/transient ischemic attack, thromboembolic events, major bleeding, death, AF during follow-up, diagnosis of arrhythmia other than AF, and new diagnosis of any CVD were secondary endpoints. Endpoints were compared between patients with and without comorbidities. RESULTS: We identified 124 patients (29.1+/- 5 years). Of those, 84 were followed over 48.4 +/- 39.8 months. Comorbidities were present in 40.5%. Incidence of the primary endpoint was not different between the groups. Arrhythmias other than AF were more common in patients without comorbidities (36% vs 14.7%; P = 0.032). A supraventricular tachycardia (SVT) was found in 57.1% of patients who underwent electrophysiological testing and was treated with catheter ablation. None of those patients had AF during follow-up. CONCLUSIONS: Atrial fibrillation occurs in young patients with and without structural heart disease. Young AF patients without comorbidities rarely develop CVD during the first years after diagnosis. Yet, an SVT is found in a high proportion of young AF patients; AF may be first manifestation of SVT. Therefore, young patients should undergo further evaluation for SVT. PMID- 26848928 TI - Standardization of cryopreserved peripheral blood mononuclear cells through a resting process for clinical immunomonitoring--Development of an algorithm. AB - Flow cytometry, as a powerful tool for immunomonitoring and quality control of peripheral blood mononuclear cells (PBMCs), is routinely used in clinical studies. However, flow cytometry based assays for cryopreserved peripheral blood mononuclear cells (cPBMCs) constitute a challenge. Down-regulation of surface and intracellular markers, as well as impairment of cell function might result from cryopreservation. Furthermore, protocols for resting cPBMCs are available but diverse. Therefore, we performed a standardization of the resting process concerning resting position, cell concentration, resting period and material of cell culture tubes as well as culture media. We further investigated the influence of resting on the phenotype and functionality of T cells comparing fresh PBMCs as gold standard to rested and non-rested cPBMCs. Polychromatic flow cytometry staining, peptide-MHC class I restricted tetramer staining and intracellular cytokine staining as major methods were used. Our results revealed that a horizontal position, a cell concentration of 2 to 5 * 10(6) cells/ml and an overnight resting phase is beneficial to eliminate dead or dying cells in cPBMCs with a mean cell loss of 14% overall cell populations. In addition, the quality and quantity of regulatory T cells and antigen specific T cells recovered upon resting. For multifunctional T cells a decrease of activation threshold in the way of a twofold mean fluorescence intensity (MFI) and increase of degranulation marker CD107a, co-stimulatory marker CD28, adhesion molecule CD62L as well as the ability to secrete antiviral cytokines like interferon gamma (IFN gamma), tumor necrosis factor (TNF), and interleukin 2 (IL-2) comparable to fresh PBMCs were observed. However, based upon our data resting is not helpful for the flow cytometric analyses of myeloid-derived suppressor cells (MDSCs) and large/intermediate size lymphocytes which rather decreased/vanished ex vivo. Therefore, we developed an algorithm to indicate for which cell population and for which type of analyses the resting process is useful or not. PMID- 26848931 TI - Blood pressure and the capacity-load model in 8-year-old children from Nepal: Testing the contributions of kidney size and intergenerational effects. AB - OBJECTIVES: Growth patterns in early life are increasingly linked with subsequent cardio-metabolic risk, but the underlying mechanisms require elucidation. We have developed a theoretical model of blood pressure, treating it as a function of homeostatic metabolic capacity, and antagonistic metabolic load. We sought to differentiate prenatal and postnatal components of metabolic capacity, and to identify intergenerational contributions to offspring capacity and load. METHODS: We followed up at 8 years a cohort of children originally recruited into a randomized trial of maternal micronutrient supplementation in pregnancy. Maternal anthropometry was measured at recruitment. Offspring anthropometry was measured at birth, 2 years and 8 years. Offspring blood pressure, kidney size, and body composition were measured at 8 years. Regression analysis was used to investigate potential associations of maternal phenotype, birth phenotype, and current body composition with kidney size and blood pressure. RESULTS: Blood pressure was positively associated with body fat, but negatively associated with birth weight and relative leg length. Kidney size was positively associated with birth weight but not with relative leg length. Adjusting for adiposity, blood pressure was independently negatively associated with birth weight, relative leg length, and kidney length. Maternal height and BMI predicted offspring size at birth and at 8 years, but not blood pressure. CONCLUSIONS: Our data provide support for the capacity-load model of blood pressure in Nepalese children. Fetal and postnatal growth and kidney dimensions all contribute to metabolic capacity. Maternal phenotype contributed to offspring capacity and load, but these associations did not propagate to blood pressure. Am. J. Hum. Biol. 28:555-565, 2016. (c) 2016 The Authors American Journal of Human Biology Published by Wiley Periodicals, Inc. PMID- 26848933 TI - Understanding Nanostructuring Processes in Thermoelectrics and Their Effects on Lattice Thermal Conductivity. AB - Cooling rates of molten PbTe-CdTe compositions play a determinant role in defining the nanoscale precipitate size distribution and the corresponding number densities, resulting in distinct trends of lattice thermal conductivity evolution with varying CdTe fractions. PMID- 26848932 TI - Maternal Dietary Patterns are Associated with Lower Levels of Cardiometabolic Markers during Pregnancy. AB - BACKGROUND: Elevated levels of cardiometabolic markers are characteristic of normal pregnancy, however, insulin resistance and increased glucose, triglyceride, and cholesterol levels can adversely influence maternal and child health. Diet is a modifiable behaviour that could have significant impact on maternal cardiometabolic levels during pregnancy. We investigated the association between dietary patterns and cardiometabolic markers (glucose, insulin, insulin resistance (HOMA-IR), triglycerides, and cholesterol) during pregnancy. METHODS: Data from the Pregnancy, Infection, and Nutrition prospective cohort study (2000 05) was used (n = 513). Diet was assessed using a food frequency questionnaire. Dietary patterns were derived using latent class analysis (LCA) and the Dietary Approaches to Stop Hypertension (DASH) diet. Linear regression was used to examine the dietary patterns-cardiometabolic markers association during pregnancy. RESULTS: Three dietary patterns evolved from the LCA characterised by high intakes of: (1) hamburgers, hot dogs, bacon, French fries, fried chicken, white bread, and soft drinks; (2) some vegetables, fruit juice, refined grains, mixed dishes, processed meat, and empty calorie foods; and (3) fruits, vegetables, whole grains, low-fat dairy, breakfast bars, and water. After adjustment for potential confounders including prepregnancy body mass index, a diet consistent with Latent Class 3 was negatively associated with maternal insulin (MUU/mL: beta = -0.12; 95% CI -0.23, -0.01) and HOMA-IR (beta = -0.13; 95% CI -0.25, -0.00). Additionally, DASH scores within Tertile 3 (higher dietary quality) were also negatively associated with maternal triglycerides (mg/dL). CONCLUSIONS: The study findings suggest an association between maternal dietary patterns and several cardiometabolic markers during pregnancy. PMID- 26848934 TI - The Calculating Boluses on Multiple Daily Injections (CBMDI) study: A randomized controlled trial on the effect on metabolic control of adding a bolus calculator to multiple daily injections in people with type 1 diabetes. AB - BACKGROUND: Although the insulin bolus calculator is increasingly being used by people with type 1 diabetes (T1D) on multiple daily injection (MDI) therapy, few studies have investigated its effects on glycemic control. The aim of this study was to determine whether adding this device to therapeutic intensification could further improve metabolic control. METHODS: A 4-month randomized controlled clinical trial was performed comparing subjects undergoing therapeutic intensification and either using the bolus calculator (Cb group) or not (active control [Co] group). Metabolic control, fear of hypoglycemia, and treatment acceptance were evaluated. RESULTS: In all, 70 people completed the study (42 in the Cb group, 28 in the Co group). There was a significant decrease in HbA1c in both the Cb and Co groups (-7 mmol/mol [-0.7 %] vs -4 mmol/mol [-0.4 %], respectively). There were no significant differences in HbA1c at baseline or the end of the study, or in the decrease in HbA1c, glycemia, or changes in blood glucose levels at the end of the study between the two groups. There was a significant increase in the number of participants with good metabolic control (HbA1c <58 mmol/mol [7.5 %]) in the Cb group (from 16.7 % to 40.5 %), but not in the Co group. The incidence of hypoglycemic events was reduced slightly but significantly only in the Cb group. There was no change in the fear of hypoglycemia at the end of the study. The bolus calculator was well accepted. CONCLUSIONS: In T1D, adding a bolus calculator to intensive MDI resulted in a significant improvement in metabolic control and slightly decreased the number of hypoglycemic episodes. Metabolic control also improved in the Co group. PMID- 26848935 TI - Behavioral and cardiopulmonary effects of dexmedetomidine alone and in combination with butorphanol, methadone, morphine or tramadol in conscious sheep. AB - OBJECTIVE: To compare cardiopulmonary and sedative effects following administration of dexmedetomidine alone or with butorphanol, methadone, morphine or tramadol in healthy sheep. STUDY DESIGN: Randomized crossover study. ANIMALS: Six Santa Ines sheep, five females, one male, aged 12-28 months and weighing 40.1 +/- 6.2 kg. METHODS: Sheep were assigned treatments of dexmedetomidine (0.005 mg kg(-1) ; D); D and butorphanol (0.15 mg kg(-1) ; DB); D and methadone (0.5 mg kg( 1) ; DM); D and morphine (0.5 mg kg(-1) ; DMO); or D and tramadol (5.0 mg kg(-1) ; DT). All drugs were administered intravenously with at least 7 days between each treatment. Rectal temperature, heart rate (HR), respiratory rate (fR ), invasive arterial pressure, blood gases and electrolytes were measured prior to administration of drugs (baseline, T0) and every 15 minutes following drug administration for 120 minutes (T15-T120). Sedation was scored by three observers blinded to treatment. RESULTS: HR decreased in all treatments and fR decreased in DM at T30 and DMO at T30 and T45. PaCO2 was increased in D, DB and DM compared with baseline, and PaO2 decreased in D at T15 and T45; in DB at T15 to T75; in DM at T15 to T60; in DMO at T15; and in DT at T15, T30 and T75. There was a decrease in temperature in D, DB and DM. An increased pH was measured in D at all time points and in DT at T30-T120. HCO3- and base excess were increased in all treatments compared with baseline. There were no statistical differences in sedation scores. CONCLUSIONS AND CLINICAL RELEVANCE: The combination of dexmedetomidine with butorphanol, methadone, morphine or tramadol resulted in similar changes in cardiopulmonary function and did not improve sedation when compared with dexmedetomidine alone. PMID- 26848936 TI - Emerging evidence for a discrete genital site for orgasm? PMID- 26848937 TI - Measuring the impact of non-monetary incentives on facility delivery in rural Zambia: a clustered randomised controlled trial. AB - OBJECTIVES: In Zambia, only 56% of rural women deliver in a health facility, and improving facility delivery rates is a priority of the Zambian government. 'Mama kit' incentives - small packages of childcare items provided to mothers conditional on delivering their baby in a facility - may encourage facility delivery. This study measured the impact and cost-effectiveness of a US$4 mama kit on rural facility delivery rates in Zambia. METHODS: A clustered randomised controlled trial was used to measure the impact of mama kits on facility delivery rates in thirty rural health facilities in Serenje and Chadiza districts. Facility-level antenatal care and delivery registers were used to measure the percentage of women attending antenatal care who delivered at a study facility during the intervention period. Results from the trial were then used to model the cost-effectiveness of mama kits at-scale in terms of cost per death averted. RESULTS: The mama kits intervention resulted in a statistically significant increase in facility delivery rates. The multivariate logistic regression found that the mama kits intervention increased the odds of delivering at a facility by 63% (P-value < 0.01, 95% CI: 29%, 106%), or an increase of 9.9 percentage points, yielding a cost-effectiveness of US$5183 per death averted. CONCLUSIONS: This evaluation confirms that low-cost mama kits can be a cost-effective intervention to increase facility delivery rates in rural Zambia. Mama kits alone are unlikely to completely solve safe delivery challenges but should be embedded in larger maternal and child health programmes. PMID- 26848938 TI - Least squares regression methods for clustered ROC data with discrete covariates. AB - The receiver operating characteristic (ROC) curve is a popular tool to evaluate and compare the accuracy of diagnostic tests to distinguish the diseased group from the nondiseased group when test results from tests are continuous or ordinal. A complicated data setting occurs when multiple tests are measured on abnormal and normal locations from the same subject and the measurements are clustered within the subject. Although least squares regression methods can be used for the estimation of ROC curve from correlated data, how to develop the least squares methods to estimate the ROC curve from the clustered data has not been studied. Also, the statistical properties of the least squares methods under the clustering setting are unknown. In this article, we develop the least squares ROC methods to allow the baseline and link functions to differ, and more importantly, to accommodate clustered data with discrete covariates. The methods can generate smooth ROC curves that satisfy the inherent continuous property of the true underlying curve. The least squares methods are shown to be more efficient than the existing nonparametric ROC methods under appropriate model assumptions in simulation studies. We apply the methods to a real example in the detection of glaucomatous deterioration. We also derive the asymptotic properties of the proposed methods. PMID- 26848939 TI - Cooperation of Aspergillus nidulans enzymes increases plant polysaccharide saccharification. AB - Efficient polysaccharide degradation depends on interaction between enzymes acting on the main chain and the side chains. Previous studies demonstrated cooperation between several enzymes, but not all enzyme combinations have been explored. A better understanding of enzyme cooperation would enable the design of better enzyme mixtures, optimally profiting from synergistic effects. In this study, we analyzed the cooperation of several enzymes involved in the degradation of xylan, glucan, xyloglucan and crude plant biomass from Aspergillus nidulans by single and combined incubations with their polymeric substrate. Positive effects were observed between most enzymes, although not always to the same extent. Moreover, the tailor made cocktails formulated in this study resulted in efficient release of glucose from plant biomass. This study also serves as an example for the complex cooperation that occurs between enzymes in plant biomass saccharification and how expression in easily-accessible hosts, such as Pichia pastoris, can help in revealing these effects. PMID- 26848940 TI - Comparison of Maximum Intercuspal Contacts of Articulated Casts and Virtual Casts Requiring Posterior Fixed Partial Dentures. AB - PURPOSE: To evaluate the accuracy of the CEREC CAD/CAM system in reproducing the maximum intercuspal contacts of the casts, which include posterior teeth preparation for a fixed partial denture (FPD). MATERIALS AND METHODS: Ten pairs of gypsum casts were mounted in articulators in maximum intercuspal position (MIP) to serve as patient simulation models. Tooth #19 was removed from the cast. Occlusal contacts in MIP were identified with articulating paper, and digital impressions of the casts with unprepared teeth and buccal images in MIP were taken. Teeth #18 and #20 were prepared for an FPD, and full- and half-arch digital impressions of the casts with prepared teeth and buccal images from different sides were taken. In each situation, screenshot images of the virtual casts with occlusal contacts were saved as JPEG files. The proportions of congruence of virtual contacts with cast contacts were analyzed by superimposing screenshot images of the virtual casts onto the screenshot images of the casts with the indicated occlusal contacts in a transparent manner using an image processing program. The data were statistically analyzed with a paired t-test. RESULTS: The highest percentages of virtually indicated contacts identical to the cast contacts were observed in non-prepared full-arch digital impressions. Comparison of full-arch impressions taken before and after tooth preparation showed no difference for congruence even if the buccal image was taken from the contralateral or ipsilateral side (p > 0.05). After tooth preparation, comparing full- and half-arch digital impressions revealed that half-arch impression showed significantly lower percentages of identical contacts (p < 0.05). When comparing the buccal image side, no significant difference was detected between ipsilateral and contralateral images both for non-prepared and prepared casts (p > 0.05). CONCLUSION: When there is no posterior antagonist contact following tooth preparation for an FPD, taking a full-arch digital impression and designing the restoration on full-arch virtual models can be advocated. PMID- 26848941 TI - Establishment of a proficiency panel for an external quality assessment programme for the detection of bacterial contamination in platelet concentrates using rapid and cultural detection methods. AB - BACKGROUND: Platelet concentrates (PCs) are the main focus regarding the residual risk of transfusion-transmitted bacterial infections. Rapid screening methods for bacterial detection in platelets have been optimized over the last decade, but their external evaluation represents a complicated process. We developed a new type of proficiency panel for bacterial detection in PCs using currently available screening methods (especially rapid methods) suitable for external quality assessment programmes (EQAP). METHODS: PC samples were inoculated with different bacteria at two concentrations (10E+03 CFU/ml, 10E+05 CFU/ml) and stored under temperature-controlled conditions (1-5 days). Bacterial growth was further prevented by the addition of 0-20 MUg/ml cotrimoxazole. Samples were analysed prior to and after storage using rapid detection methods (Bactiflow (BF), bacteria-generic NAT) and cultural methods to determine the influence of storage and antibiotic treatment on bacterial counts and the result outcome. A pilot EQAP was performed with four participants. RESULTS: Testing under the evaluated conditions demonstrated that bacterial counts remained constant prior to and after storage. The supplementation of 10 MUg/ml cotrimoxazole did not influence bacterial detection using the two rapid detection methods BF and NAT. Furthermore, the detection of bacteria using cultural methods is still possible despite of antibiotic supplementation. The pilot EQAP confirmed these results. A storage time of up to 3 days proved practicable, showing no considerable influence on bacterial count and outcome of test results. CONCLUSION: The established proficiency panel provided PC matrix-conform samples with stabilized bacterial counts which can be analysed in parallel by rapid and cultural detection methods. PMID- 26848942 TI - Activation of autophagy through calcium-dependent AMPK/mTOR and PKCtheta pathway causes activation of rat hepatic stellate cells under hypoxic stress. AB - The activation of hepatic stellate cells (HSCs) is a prominent event in liver fibrogenesis. However, how HSCs are activated in the hypoxic microenvironment remains unclear. Here, we found that hypoxia increased autophagy in rat HSCs. Moreover, hypoxia induced an elevation of the intracellular calcium concentration ([Ca(2+)]i), which was abolished by the cytosolic Ca(2+) chelator or the phospholipase C (PLC)-specific inhibitor. Furthermore, hypoxia-induced autophagy involved the calcium-dependent activation of the 5'-adenosine monophosphate activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR) and protein kinase C-theta (PKCtheta) pathways. In addition, hypoxia-mediated activation of HSCs depended on autophagy. Our results suggest that autophagy induction via the calcium-dependent AMPK-mTOR and PKCtheta pathways might lead to the activation of HSCs during hypoxic stress. PMID- 26848943 TI - Epicardial fat: a new cardiovascular therapeutic target. AB - Epicardial fat is the visceral fat depot of the heart. Given its rapid metabolism, organ fat specificity and simple objective measurability, epicardial fat can serve as target for pharmaceutical agents targeting the adipose tissue. Epicardial fat has shown to significantly respond to thiazolidinediones, glucagon like peptide 1 receptor agonists, dipeptidyl peptidase-4 inhibitors and statins. Epicardial fat may represent a measurable risk factor and modifiable therapeutic target. Targeted pharmaceutical interventions may allow the epicardial fat to resume its physiological role. A drug-induced browning effect on epicardial fat suggests the development of pharmacological strategies to increase energy consumption. The potential of modulating the epicardial fat transcriptome with targeted pharmacological agents can open new avenues in the pharmacotherapy of cardio-metabolic diseases. PMID- 26848944 TI - Stem cells and exosomes in cardiac repair. AB - Cardiac diseases currently lead in the number of deaths per year, giving rise an interest in transplanting embryonic and adult stem cells as a means to improve damaged tissue from conditions such as myocardial infarction and coronary artery disease. After testing these cells as a treatment option in both animal and human models, it is believed that these cells improve the damaged tissue primarily through the release of autocrine and paracrine factors. Major concerns such as teratoma formation, immune response, difficulty harvesting cells, and limited cell proliferation and differentiation, hinder the routine use of these cells as a treatment option in the clinic. The advent of stem cell-derived exosomes circumvent those concerns, while still providing the growth factors, miRNA, and additional cell protective factors that aid in repairing and regenerating the damaged tissue. These exosomes have been found to be anti-apoptotic, anti fibrotic, pro-angiogenic, as well as enhance cardiac differentiation, all of which are key to repairing damaged tissue. As such, stem cell derived exosomes are considered to be a potential new and novel approach in the treatment of various cardiac diseases. PMID- 26848945 TI - Small is Beautiful: Challenges and Perspectives of Nano/Meso/Microscience. AB - This article gives a personal view on the development of our discipline, but also tries to elaborate some of the current and future trends to illustrate why "Small science" is at the core of the current scientific development of chemistry and physics. Topics such as the limits of 'small', new modes of self-organization, pattern recognition, self-repair, encoding of structures, and the appropriate handling of complexity are discussed along these lines. PMID- 26848946 TI - A simple and effective method for making multipotent/multilineage scaffolds with hydrophilic nature without any postmodification/treatment. AB - A number of biodegradable and bioresorbable materials, as well as scaffold designs, have been experimentally and/or clinically studied for tissue engineering of diverse tissue types. Cell-material responses are strongly dependent on the properties of the scaffold material. In this study, scaffolds based on polycaprolactone (PCL) and PCL blended with a triblock copolymer, Polycaprolactone-polytetrahydrofuran-polycaprolactone (PCL-PTHF-PCL) at different ratios were fabricated by electrospinning. Blending and electrospinning of the triblock copolymer with PCL generated a super hydrophilic scaffold, the mechanical and biological properties of which varied with the concentration of the triblock copolymer. The hydrophilicity of the electrospun scaffolds was determined by measurement of water-air contact angle. Cellular response to the electrospun scaffolds was studied by seeding two types of cells, L929 fibroblast cell line and rat mesenchymal stem cells (RMSC). We observed that the super hydrophilicity of the material did not prevent cell adhesion, while the cell proliferation was low or negligible for scaffolds containing higher amount of PCL PTHF-PCL. Chondrogenic differentiation of RMSC was found to be better on the PCL blend containing 10% (w/v) of PCL-PTHF-PCL than the bare PCL. Our studies indicate that the cellular response is dependent on the biomaterial composition and highlight the importance of tailoring the scaffold properties for applications in tissue engineering and regenerative medicine. PMID- 26848947 TI - Bioinspired Protein Channel-Based Scanning Ion Conductance Microscopy (Bio-SICM) for Simultaneous Conductance and Specific Molecular Imaging. AB - The utility of stochastic single-molecule detection using protein nanopores has found widespread application in bioanalytical sensing as a result of the inherent signal amplification of the resistive pulse method. Integration of protein nanopores with high-resolution scanning ion conductance microscopy (SICM) extends the utility of SICM by enabling selective chemical imaging of specific target molecules, while simultaneously providing topographical information about the net ion flux through a pore under a concentration gradient. In this study, we describe the development of a bioinspired scanning ion conductance microscopy (bio-SICM) approach that couples the imaging ability of SICM with the sensitivity and chemical selectivity of protein channels to perform simultaneous pore imaging and specific molecule mapping. To establish the framework of the bio-SICM platform, we utilize the well-studied protein channel alpha-hemolysin (alphaHL) to map the presence of beta-cyclodextrin (betaCD) at a substrate pore opening. We demonstrate concurrent pore and specific molecule imaging by raster scanning an alphaHL-based probe over a glass membrane containing a single 25-MUm-diameter glass pore while recording the lateral positions of the probe and channel activity via ionic current. We use the average channel current to create a conductance image and the raw current-time traces to determine spatial localization of betaCD. With further optimization, we believe that the bio-SICM platform will provide a powerful analytical methodology that is generalizable, and thus offers significant utility in a myriad of bioanalytical applications. PMID- 26848948 TI - Comparison of D-gluconic acid production in selected strains of acetic acid bacteria. AB - The oxidative metabolism of acetic acid bacteria (AAB) can be exploited for the production of several compounds, including D-gluconic acid. The production of D gluconic acid in fermented beverages could be useful for the development of new products without glucose. In the present study, we analyzed nineteen strains belonging to eight different species of AAB to select those that could produce D gluconic acid from D-glucose without consuming D-fructose. We tested their performance in three different media and analyzed the changes in the levels of D glucose, D-fructose, D-gluconic acid and the derived gluconates. D-Glucose and D fructose consumption and D-gluconic acid production were heavily dependent on the strain and the media. The most suitable strains for our purpose were Gluconobacter japonicus CECT 8443 and Gluconobacter oxydans Po5. The strawberry isolate Acetobacter malorum (CECT 7749) also produced D-gluconic acid; however, it further oxidized D-gluconic acid to keto-D-gluconates. PMID- 26848949 TI - Evaluation of real-time PCR coupled with immunomagnetic separation or centrifugation for the detection of healthy and sanitizer-injured Salmonella spp. on mung bean sprouts. AB - Fresh mung bean sprouts have been identified as a source of many Salmonella outbreaks worldwide. The aim of this study was to develop a rapid and accurate detection methodology for low levels of healthy and sanitizer-injured Salmonella on mung bean sprouts using real-time PCR coupled with either immunomagnetic separation (PCR-IMS) or centrifugation (PCR-cen). Initially, three parameters of IMS; specificity/sensitivity, bacterial concentration and bead incubation time were optimized. Secondly, limit of detection (LOD) was determined for the optimized PCR-IMS and PCR-cen. These two methods were compared against PCR alone (PCR) and the standard culture method (ISO) for their ability to detect Salmonella using inoculated and uninoculated sprouts. Under optimum IMS conditions (10(5)CFU/ml for 30 min), capture efficiency of Salmonella in sprout suspensions was lower than 40%, most probably due to the non-specific binding of the background microbiota. PCR-IMS and PCR-cen had a similar LOD at 10(3)CFU/ml, which was one log unit lower than PCR. Enrichment of 10h was sufficient to detect 100% of the inoculated sprouts with both PCR-IMS and PCR-cen, which was significantly faster compared to PCR and the ISO method. Moreover, the validation study using uninoculated sprouts revealed that PCR-IMS and PCR-cen were equally effective on Salmonella detection, showing 98.3% accuracy. These results suggest that PCR-cen would be the effective and less costly method for the detection of both healthy and sanitizer-injured Salmonella on mung bean sprouts. PMID- 26848950 TI - Planetary Protection and Mars Special Regions--A Suggestion for Updating the Definition. AB - We highlight the role of COSPAR and the scientific community in defining and updating the framework of planetary protection. Specifically, we focus on Mars "Special Regions," areas where strict planetary protection measures have to be applied before a spacecraft can explore them, given the existence of environmental conditions that may be conducive to terrestrial microbial growth. We outline the history of the concept of Special Regions and inform on recent developments regarding the COSPAR policy, namely, the MEPAG SR-SAG2 review and the Academies and ESF joint committee report on Mars Special Regions. We present some new issues that necessitate the update of the current policy and provide suggestions for new definitions of Special Regions. We conclude with the current major scientific questions that remain unanswered regarding Mars Special Regions. PMID- 26848951 TI - Differential Requirement for Pten Lipid and Protein Phosphatase Activity during Zebrafish Embryonic Development. AB - The lipid- and protein phosphatase PTEN is one of the most frequently mutated tumor suppressor genes in human cancers and many mutations found in tumor samples directly affect PTEN phosphatase activity. In order to understand the functional consequences of these mutations in vivo, the aim of our study was to dissect the role of Pten phosphatase activities during zebrafish embryonic development. As in other model organisms, zebrafish mutants lacking functional Pten are embryonically lethal. Zebrafish have two pten genes and pten double homozygous zebrafish embryos develop a severe pleiotropic phenotype around 4 days post fertilization, which can be largely rescued by re-introduction of pten mRNA at the one-cell stage. We used this assay to characterize the rescue-capacity of Pten and variants with mutations that disrupt lipid, protein or both phosphatase activities. The pleiotropic phenotype at 4dpf could only be rescued by wild type Pten, indicating that both phosphatase activities are required for normal zebrafish embryonic development. An earlier aspect of the phenotype, hyperbranching of intersegmental vessels, however, was rescued by Pten that retained lipid phosphatase activity, independent of protein phosphatase activity. Lipid phosphatase activity was also required for moderating pAkt levels at 4 dpf. We propose that the role of Pten during angiogenesis mainly consists of suppressing PI3K signaling via its lipid phosphatase activity, whereas the complex process of embryonic development requires lipid and protein phosphatase of Pten. PMID- 26848952 TI - Predictive Factors of Superior Mediastinal Nodal Metastasis from Papillary Thyroid Carcinoma--A Prospective Observational Study. AB - OBJECTIVES: The purpose of this study was to demonstrate the incidence rates and predictive factors of superior mediastinal lymph node (SMLN) metastasis in PTC (papillary thyroid carcinoma) patients. METHODS: A prospective observational study was performed between January 2009 and January 2011. PTC patients who had tumors with a maximal diameter greater than 1 cm and clinically negative SMLNs were included in this study. Finally, a total of 217 patients who underwent total thyroidectomy with central compartment neck dissection (CND) and elective superior mediastinal lymph node dissection (SMLND), with or without modified radical neck dissection (MRND) and revisional CND, were included. RESULTS: Occult SMLN metastasis was present in 15.7% (34/217). Cytological classifications of tumor, BRAFV600E mutation, Tumor size, T-stage, perithyroidal extension, lymphovascular invasion, multifocality, and paratracheal pN(+) were not predictive of SMLN metastasis (P > .05), while revision surgery, pretracheal pN(+), and multiple lateral pN(+) were associated with SMLN metastasis. There were no major complications related to SMLND. Transient and permanent hypoparathyroidism was observed in 69 cases (31.8%) and 8 cases (3.6%), respectively. CONCLUSIONS: Despite clinically negative SMLN in preoperative evaluation, SMLN metastasis can be predicted for patients with a PTC tumor size larger than 1 cm, pretracheal LN metastasis, multiple lateral metastasis, and revisional surgery. PMID- 26848953 TI - Hypothermia Protects and Prolongs the Tolerance Time of Retinal Ganglion Cells against Ischemia. AB - PURPOSE: Hypothermia has been shown to be neuroprotective in the therapy of ischemic stroke in the brain. To date no studies exist on the level of the inner retina and it is unclear if hypothermia would prolong the ischemic tolerance time of retinal ganglion cells, which are decisive in many ischemic retinopathies. METHODS: Bovine eyes were enucleated and stored either at 21 degrees C or 37 degrees C for 100 or 340 minutes, respectively. Afterwards the globes were dissected, the retina was prepared and either the spontaneous ganglion cell responses were measured or the retina was incubated as an organotypic culture for additional 24 hours. After incubation the retina was either processed for histology (H&E and DAPI staining) or real-time PCR (Thy-1 expression) was performed. RESULTS: Hypothermia prolonged ganglion cell survival up to 340 minutes under ischemic conditions. In contrast to eyes kept at 37 degrees C the eyes stored at 21 degrees C still showed spontaneous ganglion cell spiking (56.8% versus 0%), a 5.8 fold higher Thy-1 mRNA expression (not significant, but a trend) and a preserved retinal structure after 340 minutes of ischemia. CONCLUSION: Hypothermia protects retinal ganglion cells against ischemia and prolongs their ischemic tolerance time. PMID- 26848954 TI - Socially Driven Consistent Behavioural Differences during Development in Common Ravens and Carrion Crows. AB - Consistent individual differences in behaviour, or 'personality', are likely to be influenced by development, social context, and species ecology, though few comparative, longitudinal studies exist. Here, we investigated the role of development and social context on personality variation in two identically reared, social corvids: common ravens and carrion crows. We repeatedly presented subjects with a variety of novel food and objects, while alone and in a primarily sibling subgroup, from fledging to sub-adulthood. We predicted that consistent individual differences would emerge later in development, and that conspecific presence would facilitate behavioural similarities. In contrast to our predictions, we found that individuals of both species were highly inconsistent in their behavioural responses throughout the development period. In line with our predictions, though in the ravens only, conspecific presence promoted behavioural similarities as individuals were strongly shaped by their subgroup, and it is likely that these effects were driven by social context rather than relatedness. We discuss these findings in relation to developmental steps and the role of social relations in these species. Overall, our findings highlight that these two species are highly adaptable in their behaviour, and the ravens in particular are strongly influenced by their social environment, which may facilitate cooperation and social learning. PMID- 26848955 TI - In Vitro Reconstruction of Neuronal Networks Derived from Human iPS Cells Using Microfabricated Devices. AB - Morphology and function of the nervous system is maintained via well-coordinated processes both in central and peripheral nervous tissues, which govern the homeostasis of organs/tissues. Impairments of the nervous system induce neuronal disorders such as peripheral neuropathy or cardiac arrhythmia. Although further investigation is warranted to reveal the molecular mechanisms of progression in such diseases, appropriate model systems mimicking the patient-specific communication between neurons and organs are not established yet. In this study, we reconstructed the neuronal network in vitro either between neurons of the human induced pluripotent stem (iPS) cell derived peripheral nervous system (PNS) and central nervous system (CNS), or between PNS neurons and cardiac cells in a morphologically and functionally compartmentalized manner. Networks were constructed in photolithographically microfabricated devices with two culture compartments connected by 20 microtunnels. We confirmed that PNS and CNS neurons connected via synapses and formed a network. Additionally, calcium-imaging experiments showed that the bundles originating from the PNS neurons were functionally active and responded reproducibly to external stimuli. Next, we confirmed that CNS neurons showed an increase in calcium activity during electrical stimulation of networked bundles from PNS neurons in order to demonstrate the formation of functional cell-cell interactions. We also confirmed the formation of synapses between PNS neurons and mature cardiac cells. These results indicate that compartmentalized culture devices are promising tools for reconstructing network-wide connections between PNS neurons and various organs, and might help to understand patient-specific molecular and functional mechanisms under normal and pathological conditions. PMID- 26848956 TI - Personalised Prescription of Scalable High Intensity Interval Training to Inactive Female Adults of Different Ages. AB - Stepping is a convenient form of scalable high-intensity interval training (HIIT) that may lead to health benefits. However, the accurate personalised prescription of stepping is hampered by a lack of evidence on optimal stepping cadences and step heights for various populations. This study examined the acute physiological responses to stepping exercise at various heights and cadences in young (n = 14) and middle-aged (n = 14) females in order to develop an equation that facilitates prescription of stepping at targeted intensities. Participants completed a step test protocol consisting of randomised three-minute bouts at different step cadences (80, 90, 100, 110 steps.min-1) and step heights (17, 25, 30, 34 cm). Aerobic demand and heart rate values were measured throughout. Resting metabolic rate was measured in order to develop female specific metabolic equivalents (METs) for stepping. Results revealed significant differences between age groups for METs and heart rate reserve, and within-group differences for METs, heart rate, and metabolic cost, at different step heights and cadences. At a given step height and cadence, middle-aged females were required to work at an intensity on average 1.9 +/- 0.26 METs greater than the younger females. A prescriptive equation was developed to assess energy cost in METs using multilevel regression analysis with factors of step height, step cadence and age. Considering recent evidence supporting accumulated bouts of HIIT exercise for health benefits, this equation, which allows HIIT to be personally prescribed to inactive and sedentary women, has potential impact as a public health exercise prescription tool. PMID- 26848957 TI - High Resolution Esophageal Manometry in Patients with Chagas Disease: A Cross Sectional Evaluation. AB - INTRODUCTION: Gastrointestinal involvement affects 30-40% of the patients with chronic Chagas disease. Esophageal symptoms appear once the structural damage is established. Little is known about the usefulness of high resolution manometry to early identification of esophageal involvement. METHOD: We performed a cross sectional study at the Vall d'Hebron University Hospital (Barcelona, Spain) between May 2011 and April 2012. Consecutive patients diagnosed with Chagas disease in the chronic phase were offered to participate. All patients underwent a structured questionnaire about digestive symptoms, a barium esophagogram (Rezende classification) and an esophageal high resolution manometry (HRM). A control group of patients with heartburn who underwent an esophageal HRM in our hospital was selected. RESULTS: 62 out of 73 patients that were included in the study fulfilled the study protocol. The median age of the Chagas disease group (CG) was 37 (IQR 32-45) years, and 42 (67.7%) patients were female. Twenty-seven (43.5%) patients had esophageal symptoms, heartburn being the most frequent. Esophagogram was abnormal in 5 (8.77%). The esophageal HRM in the CG showed a pathological motility pattern in 14 patients (22.6%). All of them had minor disorders of the peristalsis (13 with ineffective esophageal motility and 1 with fragmented peristalsis). Hypotonic lower esophageal sphincter was found more frequently in the CG than in the control group (21% vs 3.3%; p<0.01). Upper esophageal sphincter was hypertonic in 22 (35.5%) and hypotonic in 1 patient. When comparing specific manometric parameters or patterns in the CG according to the presence of symptoms or esophagogram no statistically significant association were seen, except for distal latency. CONCLUSION: The esophageal involvement measured by HRM in patients with chronic Chagas disease in our cohort is 22.6%. All the patients with esophageal alterations had minor disorders of the peristalsis. Symptoms and esophagogram results did not correlate with the HRM results. PMID- 26848958 TI - Correction: Lycopene and Beta-Carotene Induce Growth Inhibition and Proapoptotic Effects on ACTH-Secreting Pituitary Adenoma Cells. PMID- 26848959 TI - Feeding Strategies of Brown Howler Monkeys in Response to Variations in Food Availability. AB - Primates display varying degrees of behavioral flexibility that allow them to adjust their diet to temporal changes in food availability. This trait might be critical for the survival of folivorous-frugivorous species inhabiting small forest fragments, where the availability of food resources tends to be lower than in large fragments and continuous forests. However, the scarcity of studies addressing this issue hampers our understanding of the adaptive behaviors that favor the survival of these primates in low-quality habitats. We conducted a 36 mo study testing the hypothesis that brown howler monkeys (Alouatta guariba clamitans) are able to adjust their diet in response to local and seasonal changes in resource availability. We compared the diet of six free-ranging groups inhabiting three small (<10 ha) and three large (>90 ha) Atlantic forest fragments in southern Brazil and estimated the temporal availability of their top food species (i.e., those species that together contribute >=80% of total feeding records). We found that brown howlers exploited similarly rich diets in small (45, 54, and 57 plant species) and large (48, 51, and 56 species) fragments. However, intermonth diet similarity was higher for groups in small fragments, where howlers also fed on plant items from nine alien species. Fruits and leaves were the most consumed plant items in both small (42% and 49% of feeding records, respectively) and large (51% and 41%, respectively) fragments. The consumption of young leaves was higher in small than in large fragments, whereas the consumption of other plant items did not show a pattern related to fragment size. Regarding the contribution of growth forms as food sources, only the exploitation of palms showed a pattern related to fragment size. Palms contributed more to the diet of groups inhabiting large fragments. The availability of seasonal food items-ripe fruits and young leaves-influenced their consumption in both habitat types. Therefore, brown howlers cope with local and seasonal fluctuations in food availability by opportunistically exploiting resources. We believe that this feeding flexibility is a key component of the phenotypic plasticity that enables howlers to thrive in disturbed habitat patches, where periods of scarcity of preferred foods shall be more common. PMID- 26848960 TI - Development of Cheaper Embryo Vitrification Device Using the Minimum Volume Method. AB - This study was designed to compare the efficiency of the Cryotop and Calibrated plastic inoculation loop (CPIL) devices for vitrification of rabbit embryos on in vitro development and implantation rate, offspring rate at birth and embryonic and fetal losses. CPIL is a simple tool used mainly by microbiologists to retrieve an inoculum from a culture of microorganisms. In experiment 1, embryos were vitrified using a Cryotop device and a CPIL device. There were no significant differences in hatched/hatching blastocyst stage rates after 48 h of culture among the vitrified groups (62 +/- 4.7% and 62 +/- 4.9%, respectively); however, the rates were significantly lower (P<0.05) than those of the fresh group (95 +/- 3.4%). In experiment 2, vitrified embryos were transferred using laparoscopic technique. The number of implanted embryos was estimated by laparoscopy as number of implantation sites at day 14 of gestation. At birth, total offspring were recorded. Embryonic and fetal losses were calculated as the difference between implanted embryos and embryos transferred and total born at birth and implanted embryos, respectively. The rate of implantation and development to term was similar between both vitrification devices (56 +/- 7.2% and 50 +/- 6.8% for implantation rate and 40 +/- 7.1% and 35 +/- 6.5% for offspring rate at birth); but significantly lower than in the fresh group (78 +/- 6.6% for implantation rate and 70 +/- 7.2% for offspring rate at birth, P<0.05). Likewise, embryonic losses were similar between both vitrification devices (44 +/ 7.2% and 50 +/- 6.8%), but significantly higher than in the fresh group (23 +/- 6.6%, P < 0.05). However, fetal losses were similar between groups (10 +/- 4.4%, 15 +/- 4.8% and 8 +/- 4.2%, for vitrified, Cryotop or CPIL and fresh, respectively). These results indicate that the CPIL device is as effective as the Cryotop device for vitrification of rabbit embryos, but at a cost of ?0.05 per device. PMID- 26848961 TI - Assessing the Effects of Bioturbation on Metal Bioavailability in Contaminated Sediments by Diffusive Gradients in Thin Films (DGT). AB - The burrowing and feeding activities of benthic organisms can alter metal speciation in sediments and affect an organisms' exposure to metals. Recently, the performance of the in situ technique of diffusive gradients in thin films (DGT) for predicting metal bioavailability has been investigated in response to the increasing demand of considering contaminant bioavailability in sediment quality assessments. In this study, we test the ability of the DGT technique for predicting the metal bioavailability in clean and contaminated sediments that are being subjected to varying degrees of sediments disturbance: low bioturbation (bivalve Tellina deltoidalis alone) and high bioturbation (bivalve and actively burrowing amphipod, Victoriopisa australiensis). Significant release of DGT labile Cd, Ni, Pb, and Zn, but lower Cu and Fe, occurred in the pore and overlying waters of sediments exposed to high bioturbation conditions, resulting in higher bioaccumulation of zinc in bivalves. Strong relationships were found between bioaccumulation of Pb and Zn and time-integrated DGT-metal fluxes, whereas poor relationships were obtained using total or dilute-acid extractable metal concentrations. This results demonstrate that DGT is a useful tool for assessing metal bioavailability in sediments and can provide useful predictions of metal bioavailable to benthic organisms in dynamic sediment environments. PMID- 26848963 TI - Evaluation of the flow of cerebrospinal fluid as well as gender and age characteristics in patients with communicating hydrocephalus, using phase contrast magnetic resonance imaging. AB - To determine the difference in the velocity parameters of cerebrospinal fluid flow in patients with varying severity of communicating hydrocephalus compared to a group of healthy volunteers without hydrodynamic disorders. The study involved 35 subjects with communicating hydrocephalus (25 subjects with Evans index of 0.31; 10 subject with Evans index of 0.46) and 62 healthy volunteers. The mean, volume, and peak flow velocities were determined at the different intracranial levels. Also were made an assessment of gender and age differences. Analysis of the differences between the mean values showed the progressive inhibition of cerebrospinal fluid outflow from the cranial cavity [in moderate communicating hydrocephalus-at 1.5 times (p < 0.05), in severe communicating hydrocephalus at 2 2.5 times (p < 0.01)], depending on the severity of enlargement of the ventricular system and, most likely, related to inhibition of its reabsorption. These changes may explain the clinical symptoms of subjects and serve as diagnostic criteria. Also it was revealed a significant influence of the factor of age on speed characteristics of the cerebrospinal fluid flow (F = 5.3303, p = 0.0003, for mean velocity). PMID- 26848962 TI - Preliminary Retrospective Analysis of Daily Tomotherapy Output Constancy Checks Using Statistical Process Control. AB - The purpose of this study was to retrospectively evaluate the results from a Helical TomoTherapy Hi-Art treatment system relating to quality controls based on daily static and dynamic output checks using statistical process control methods. Individual value X-charts, exponentially weighted moving average charts, and process capability and acceptability indices were used to monitor the treatment system performance. Daily output values measured from January 2014 to January 2015 were considered. The results obtained showed that, although the process was in control, there was an out-of-control situation in the principal maintenance intervention for the treatment system. In particular, process capability indices showed a decreasing percentage of points in control which was, however, acceptable according to AAPM TG148 guidelines. Our findings underline the importance of restricting the acceptable range of daily output checks and suggest a future line of investigation for a detailed process control of daily output checks for the Helical TomoTherapy Hi-Art treatment system. PMID- 26848964 TI - Outcome after epilepsy surgery at the University Hospitals Leuven 1998-2012. AB - We performed a retrospective outcome study of 199 patients who underwent resective epilepsy surgery from 1998 to 2012 and had a minimum of one-year follow up at the University Hospitals Leuven. Our aim was to assess seizure outcome, prognostic factors for seizure outcome and complication rate. Good seizure outcome after surgery was 38 % at 5 years and 34 % at 10 years follow-up. Good seizure outcome over the previous year at last follow-up, however, was 77 %, which could be explained by the 'running-down phenomenon', i.e. seizure freedom after initial recurrent epilepsy in 32 % of the patients, mainly after temporal lobe surgery. Good seizure outcome for at least 1 year at the last visit was 82 % for temporal and 62 % for extra-temporal lobe interventions. Other variables predictive of a good seizure outcome were not identified. Permanent complications of epilepsy surgery were observed in 31 %. The most important were word finding difficulties (22 %), depression (18 %) and memory deficits (12 %). In conclusion, epilepsy surgery is an excellent treatment option for selected patients, with a good seizure outcome in around 80 % of patients and complications in about 30 %. PMID- 26848965 TI - Prognostic ability of four clinical grading scores in spontaneous intracerebral hemorrhage. PMID- 26848966 TI - Emerging drugs and alternative possibilities in the treatment of tuberculosis. AB - INTRODUCTION: Tuberculosis (TB) remains a global health problem. Drug resistance, treatment duration, complexity, and adverse drug reactions associated with anti TB regimens are associated with treatment failure, prolonged infectiousness and relapse. With the current set of anti-TB drugs the goal to end TB has not been met. New drugs and new treatment regimens are needed to eradicate TB. AREAS COVERED: Literature was explored to select publications on drugs currently in phase II and phase III trials. These include new chemical entities, immunotherapy, established drugs in new treatment regimens and vaccines for the prophylaxis of TB. EXPERT OPINION: Well designed trials, with detailed pharmacokinetic/pharmacodynamic analysis, in which information on drug exposure and drug susceptibility of the entire anti-TB regimen is included, in combination with long-term follow-up will provide relevant data to optimize TB treatment. The new multi arm multistage trial design could be used to test new combinations of compounds, immunotherapy and therapeutic vaccines. This new approach will both reduce the number of patients exposed to inferior treatment and the financial burden. Moreover, it will speed up drug evaluation. Considering the investments involved in development of new drugs it is worthwhile to thoroughly investigate existing, non-TB drugs in new regimens. PMID- 26848967 TI - Immunity Elicited by an Experimental Vaccine Based on Recombinant Flagellin Porcine Circovirus Type 2 Cap Fusion Protein in Piglets. AB - In a recent study, we reported that a recombinant protein from fusion expression of flagellin to porcine circovirus type 2 (PCV2) Cap induced robust humoral and cell-mediated immunity that afforded full protection for PCV2 infection using BALB/c mice. Here, we further evaluated the immunogenicity and protection of the recombinant protein using specific pathogen free (SPF) pigs. Twenty-five 3-week old piglets without passively acquired immunity were divided into 5 groups. All piglets except negative controls were challenged with a virulent PCV2 at 21 days after booster vaccination and necropsied at 21 days post-challenge. Vaccination of piglets with the recombinant protein without adjuvant induced strong humoral and cellular immune responses as observed by high levels of PCV2-specific IgG antibodies and neutralizing antibodies, as well as frequencies of PCV2-specific IFN-gamma-secreting cells that conferred good protection against PCV2 challenge, with significant reduced PCV2 viremia, mild lesions, low PCV2 antigen-positive cells, as well as improved body weight gain, comparable to piglets vaccinated with a commercial PCV2 subunit vaccine. These results further demonstrated that the recombinant flagellin-Cap fusion protein is capable of inducing solid protective humoral and cellular immunity when administered to pigs, thereby becoming an effective PCV2 vaccine candidate for control of PCV2 infection. PMID- 26848968 TI - Transgenic Expression of the Formin Protein Fhod3 Selectively in the Embryonic Heart: Role of Actin-Binding Activity of Fhod3 and Its Sarcomeric Localization during Myofibrillogenesis. AB - Fhod3 is a cardiac member of the formin family proteins that play pivotal roles in actin filament assembly in various cellular contexts. The targeted deletion of mouse Fhod3 gene leads to defects in cardiogenesis, particularly during myofibrillogenesis, followed by lethality at embryonic day (E) 11.5. However, it remains largely unknown how Fhod3 functions during myofibrillogenesis. In this study, to assess the mechanism whereby Fhod3 regulates myofibrillogenesis during embryonic cardiogenesis, we generated transgenic mice expressing Fhod3 selectively in embryonic cardiomyocytes under the control of the beta-myosin heavy chain (MHC) promoter. Mice expressing wild-type Fhod3 in embryonic cardiomyocytes survive to adulthood and are fertile, whereas those expressing Fhod3 (I1127A) defective in binding to actin die by E11.5 with cardiac defects. This cardiac phenotype of the Fhod3 mutant embryos is almost identical to that observed in Fhod3 null embryos, suggesting that the actin-binding activity of Fhod3 is crucial for embryonic cardiogenesis. On the other hand, the beta-MHC promoter-driven expression of wild-type Fhod3 sufficiently rescues cardiac defects of Fhod3-null embryos, indicating that the Fhod3 protein expressed in a transgenic manner can function properly to achieve myofibril maturation in embryonic cardiomyocytes. Using the transgenic mice, we further examined detailed localization of Fhod3 during myofibrillogenesis in situ and found that Fhod3 localizes to the specific central region of nascent sarcomeres prior to massive rearrangement of actin filaments and remains there throughout myofibrillogenesis. Taken together, the present findings suggest that, during embryonic cardiogenesis, Fhod3 functions as the essential reorganizer of actin filaments at the central region of maturating sarcomeres via the actin-binding activity of the FH2 domain. PMID- 26848970 TI - Endoscopic surgery for congenital basal meningoencephaloceles in children. AB - Conclusions Endoscopic surgery is safe and effective for children with congenital basal meningoencephaloceles (CBMs); it provides an acceptable operative outcome with a short recovery time and fewer complications and may be considered as a primary approach. Objectives To explore the safety and effectiveness of using transnasal or transoral endoscopic surgery on children with CBMs. Methods The clinical data of eight CBMs children who underwent transnasal or transoral endoscopic surgery in a hospital from January 2011 to January 2015 were collected. The presenting symptoms, lesion locations, surgical outcomes, and complications were examined retrospectively. Results Of the eight children, five (62.5%) patients were male, and their ages ranged from 1 year and 6 months to 14 years (median of 9 years). Six patients presented with the transethmoidal sub type, and two presented with the transsphenoidal sub-type. The average hospital stay of all patients was 8.6 +/- 2.6 days. There were neither intra-operative nor post-operative complications observed in any of the cases during the follow-ups that occurred between 6-54 months (mean of 15.5 months). PMID- 26848969 TI - Self-Folding of Naked Segment 8 Genomic RNA of Influenza A Virus. AB - Influenza A is a negative sense RNA virus that kills hundreds of thousands of humans each year. Base pairing in RNA is very favorable, but possibilities for RNA secondary structure of the influenza genomic RNA have not been investigated. This work presents the first experimentally-derived exploration of potential secondary structure in an influenza A naked (protein-free) genomic segment. Favorable folding regions are revealed by in vitro chemical structure mapping, thermodynamics, bioinformatics, and binding to isoenergetic microarrays of an entire natural sequence of the 875 nt segment 8 vRNA and of a smaller fragment. Segment 8 has thermodynamically stable and evolutionarily conserved RNA structure and encodes essential viral proteins NEP and NS1. This suggests that vRNA self folding may generate helixes and loops that are important at one or more stages of the influenza life cycle. PMID- 26848971 TI - Late-onset CORD in a patient with RDH12 mutations identified by whole exome sequencing. PMID- 26848972 TI - Targeting an Essential GTPase Obg for the Development of Broad-Spectrum Antibiotics. AB - A promising new drug target for the development of novel broad-spectrum antibiotics is the highly conserved small GTPase Obg (YhbZ, CgtA), a protein essential for the survival of all bacteria including Neisseria gonorrhoeae (GC). GC is the agent of gonorrhea, a prevalent sexually transmitted disease resulting in serious consequences on reproductive and neonatal health. A preventive anti gonorrhea vaccine does not exist, and options for effective antibiotic treatments are increasingly limited. To address the dire need for alternative antimicrobial strategies, we have designed and optimized a 384-well GTPase assay to identify inhibitors of Obg using as a model Obg protein from GC, ObgGC. The assay was validated with a pilot screen of 40,000 compounds and achieved an average Z' value of 0.58 +/- 0.02, which suggests a robust assay amenable to high-throughput screening. We developed secondary assessments for identified lead compounds that utilize the interaction between ObgGC and fluorescent guanine nucleotide analogs, mant-GTP and mant-GDP, and an ObgGC variant with multiple alterations in the G domains that prevent nucleotide binding. To evaluate the broad-spectrum potential of ObgGC inhibitors, Obg proteins of Klebsiella pneumoniae and methicillin resistant Staphylococcus aureus were assessed using the colorimetric and fluorescence-based activity assays. These approaches can be useful in identifying broad-spectrum Obg inhibitors and advancing the therapeutic battle against multidrug resistant bacteria. PMID- 26848973 TI - Plasmid pEC156, a Naturally Occurring Escherichia coli Genetic Element That Carries Genes of the EcoVIII Restriction-Modification System, Is Mobilizable among Enterobacteria. AB - Type II restriction-modification systems are ubiquitous in prokaryotes. Some of them are present in naturally occurring plasmids, which may facilitate the spread of these systems in bacterial populations by horizontal gene transfer. However, little is known about the routes of their dissemination. As a model to study this, we have chosen an Escherichia coli natural plasmid pEC156 that carries the EcoVIII restriction modification system. The presence of this system as well as the cis-acting cer site involved in resolution of plasmid multimers determines the stable maintenance of pEC156 not only in Escherichia coli but also in other enterobacteria. We have shown that due to the presence of oriT-type F and oriT type R64 loci it is possible to mobilize pEC156 by conjugative plasmids (F and R64, respectively). The highest mobilization frequency was observed when pEC156 derivatives were transferred between Escherichia coli strains, Enterobacter cloacae and Citrobacter freundii representing coliform bacteria. We found that a pEC156-derivative with a functional EcoVIII restriction-modification system was mobilized in enterobacteria at a frequency lower than a plasmid lacking this system. In addition, we found that bacteria that possess the EcoVIII restriction modification system can efficiently release plasmid content to the environment. We have shown that E. coli cells can be naturally transformed with pEC156 derivatives, however, with low efficiency. The transformation protocol employed neither involved chemical agents (e.g. CaCl2) nor temperature shift which could induce plasmid DNA uptake. PMID- 26848974 TI - Integrin Ligation Results in Nephrin Tyrosine Phosphorylation In Vitro. AB - Nephrin is expressed at the basolateral aspect of podocytes and is an important signaling protein at the glomerular slit diaphragm. In vitro studies have demonstrated that Nephrin phosphorylation-dependent signaling is able to assemble a protein complex that is able to polymerize actin. However, proximal signaling events that result in nephrin tyrosine phosphorylation are not well understood. Nephrin deletion in mice and human nephrin mutations result in developmental failure of the podocyte intercellular junction resutling in proteinuria. This has been presumed to be due to a failure to respond to an external polarized cue in the absence of nephrin or a failure to transduce an outside-in signal in patients with nephrin mutations. The nephrin extracellular domain binds to itself or neph1 across the foot process intercellular junction. Nephrin is tyrosine phosphorylation-silent in healthy glomeruli when presumably the nephrin extracellular domain is in an engaged state. These observations raise the possibility of an alternate proximal signaling mechanism that might be responsible for nephrin tyrosine phosphorylation. Here we present data showing that integrin engagement at the basal aspect of cultured podocytes results in nephrin tyrosine phosphorylation. This is abrogated by incubating podocytes with an antibody that prevents integrin beta1 ligation and activation in response to binding to extracellular matrix. Furthermore, nephrin tyrosine phosphorylation was observed in podocytes expressing a membrane-targeted nephrin construct that lacks the extracellular domain. We propose, integrin-activation based signaling might be responsible for nephrin phosphorylation rather than engagment of the nephrin extracellular domain by a ligand. PMID- 26848975 TI - Liver Toxicity of Current Antiretroviral Regimens in HIV-Infected Patients with Chronic Viral Hepatitis in a Real-Life Setting: The HEPAVIR SEG-HEP Cohort. AB - OBJECTIVE: To assess the current frequency of ART-associated grade 3-4 transaminase elevations (TE) and grade 4 total bilirubin elevations (TBE) in HIV infected patients with chronic hepatitis B and/or C, who start a new regimen of ART. PATIENTS AND METHODS: A total of 192 pre-treated or treatment-naive HIV infected patients with HBV and/or HCV-coinfection who started ART in eight Southern Spanish centers from July/2011-December/2013, were followed for 12 months in this prospective study. RESULTS: Forty-one (21.4%) subjects had been naive to ART, median (IQR) follow-up was 11.6 (5.6-12.9) months. The most frequently initiated NRTI were tenofovir/emtricitabine [49 patients (25.5%)]. Eighty-nine (46.4%) patients started a ritonavir-boosted protease inhibitor and 77 (40.1%) individuals a NNRTI. Raltegravir and maraviroc were initiated in 24 (12.5%) and 9 (4.7%) individuals. Ten [5.21%; 95% confidence interval (CI): 2.53% 9.37%] patients presented grade 3 TE, while 8 (4.17%; 95%CI: 1.82%-8.04%) subjects showed grade 4 TBE. No episodes of grade 4 TE or ART discontinuation due to hepatotoxic events were observed. The use of ritonavir-boosted atazanavir was the only independent predictor for grade 4 TBE [adjusted odds ratio: 7.327 (95%CI: 1.417-37.89); p = 0.018] in an analysis adjusted for age, sex and baseline HIV-RNA levels, while no factor could be independently associated with grade 3-4 TE. CONCLUSIONS: Currently, the frequency of severe ART-associated TE and TBE under real-life conditions in patients with chronic viral hepatitis is similar to what has been reported previously. However, episodes of grade 4 TE are less frequent and severe TE appears to be of lesser concern. PMID- 26848976 TI - Mucin glycosylating enzyme GALNT2 suppresses malignancy in gastric adenocarcinoma by reducing MET phosphorylation. AB - Glycosylation affects malignancy in cancer. Here, we report that N- acetylgalactosaminyltransferase 2 (GALNT2), an enzyme that mediates the initial step of mucin type-O glycosylation, suppresses malignant phenotypes in gastric adenocarcinoma (GCA) by modifying MET (Hepatocyte growth factor receptor) activity. GALNT2 mRNA and protein were downregulated in GCAs, and this reduction was associated with more advanced disease stage and shorter recurrence-free survival. Suppressing GALNT2 expression in GCA cells increased cell growth, migration, and invasion in vitro, and tumor metastasis in vivo. GALNT2 knockdown enhanced phosphorylation of MET and decreased expression of the Tn antigen on MET. Inhibiting MET activity with PHA665752 decreased the malignant phenotypes caused by GALNT2 knockdown in GCA cells. Our results indicate that GALNT2 suppresses the malignant potential of GCA cells and provide novel insights into the significance of O-glycosylation in MET activity and GCA progression. PMID- 26848977 TI - MTHFD2--a new twist? PMID- 26848978 TI - Loss of oncogenic miR-155 in tumor cells promotes tumor growth by enhancing C/EBP beta-mediated MDSC infiltration. AB - The oncogenic role of microRNA-155 (miR-155) in leukemia is well established but its role in other cancers, especially breast cancer, is gradually emerging. In this study we examined the effect of mir-155 loss in a well-characterized spontaneous breast cancer mouse model where Brca1 and Trp53 are deleted by K14 Cre. miR-155 is known to be up-regulated in BRCA1-deficient tumors. Surprisingly, complete loss of miR-155 (miR-155ko/ko) did not alter the tumor free survival of the mutant mice. However, we found increased infiltration of myeloid derived suppressor cells (MDSCs) in miR-155 deficient tumors. In addition, cytokine/chemokine array analysis revealed altered level of cytokines that are implicated in the recruitment of MDSCs. Mechanistically, we identified C/EBP beta, a known miR-155 target, to regulate the expression of these cytokines in the miR-155-deficient cells. Furthermore, using an allograft model, we showed that inhibition of miR-155 in cancer cells suppressed in vivo growth, which was restored by the loss of miR-155 in the microenvironment. Taken together, we have uncovered a novel tumor suppressive function of miR-155 in the tumor microenvironment, which is also dependent on miR-155 expression in the tumor cells. Because of the oncogenic as well as tumor suppressive roles of miR-155, our findings warrant caution against a systemic inhibition of miR-155 for anticancer therapy. PMID- 26848979 TI - Aberrant epigenetic regulation in clear cell sarcoma of the kidney featuring distinct DNA hypermethylation and EZH2 overexpression. AB - The global methylation profile and the mutational status of 633 specific epigenetic regulators were analyzed in the pediatric tumor clear cell sarcoma of the kidney (CCSK). Methylation array analyses of 30 CCSKs revealed CCSK tumor DNA to be globally hypermethylated compared to Wilms tumor, normal fetal kidney, and adult kidney. The aberrant methylation pattern of CCSKs was associated with activation of genes involved in embryonic processes and with silencing of genes linked to normal kidney function. No epigenetic regulator was recurrently mutated in our cohort, but a mutation in the key epigenetic regulator EZH2 was discovered in one case. EZH2 mRNA was significantly higher in CCSK compared to Wilms tumor and normal kidney, and the EZH2 protein was strongly expressed in more than 90 % of CCSK tumor cells in 9/9 tumors analyzed. This was in striking contrast to the lack of EZH2 protein expression in Wilms tumor stromal elements, indicating that EZH2 could be explored further as a diagnostic marker and a potential drug target for CCSK. PMID- 26848980 TI - EZH2 promotes cell migration and invasion but not alters cell proliferation by suppressing E-cadherin, partly through association with MALAT-1 in pancreatic cancer. AB - Enhancer of zeste homolog 2 (EZH2) is an essential component of the polycomb repressive complex 2 (PRC2), which is required for epigenetic silencing of target genes, including those affecting cancer progression. Its role in pancreatic cancer remains to be clarified; therefore, we investigated the effects of aberrantly expressed EZH2 on pancreatic cancer. We found that EZH2 expression is up-regulated in pancreatic cancer tissues and positively correlated with lymph node metastasis and advanced clinical stage in pancreatic cancer patients. EZH2 knockdown in pancreatic cancer cell lines inhibited cell migration and invasion, but did not alter cell proliferation. Silencing of EZH2 also increased E-cadherin expression in vitro, and E-cadherin expression was inversely correlated with EZH2 expression in pancreatic cancer tissue samples. Patients with high EZH2 and low E cadherin expression had the worst prognosis. RIP and ChIP assays suggest that EZH2 is recruited to the E-cadherin promoter by the long non-coding RNA, MALAT-1 (metastasis associated in lung adenocarcinoma transcript 1), where it represses E cadherin expression. Our results show that EZH2-based therapies may be an option for the treatment of pancreatic cancer. PMID- 26848981 TI - NOTUM is a potential pharmacodynamic biomarker of Wnt pathway inhibition. AB - Activation of Wnt signaling due to Wnt overexpression or mutations of Wnt pathway components is associated with various cancers. Blocking Wnt secretion by inhibiting PORCN enzymatic activity has shown efficacy in a subset of cancers with elevated Wnt signaling. Predicting response to upstream Wnt inhibitors and monitoring response to therapeutics is challenging due to the paucity of well defined biomarkers. In this study we identify Notum as a potential biomarker for Wnt driven cancers and show that coordinate regulation of NOTUM and AXIN2 expression may be a useful predictor of response to PORCN inhibitors. Most importantly, as NOTUM is a secreted protein and its levels in blood correlate with tumor growth, it has potential as a pharmacodynamic biomarker for PORCN and other Wnt pathway inhibitors. PMID- 26848982 TI - Effects of aeration and natural zeolite on ammonium removal during the treatment of sewage by mesocosm-scale constructed wetlands. AB - The objective was to evaluate the effects of intermittent artificial aeration cycles and natural zeolite as a support medium, in addition to the contribution of plants (Schoenoplectus californicus) on NH4(+)-N removal during sewage treatment by Constructed Wetlands (CW). Two lines of Mesocosm Constructed Wetland (MCW) were installed: (a) gravel line (i.e. G-Line) and (b) zeolite line (i.e. Z Line). Aeration increased the NH4(+)-N removal efficiency by 20-45% in the G Line. Natural zeolite increased the NH4(+)-N removal efficiency by up to 60% in the Z-Line. Plants contributed 15-30% of the NH4(+)-N removal efficiency and no difference between the G-Line and the Z-Line. Conversely, the NH4(+)-N removal rate was shown to only increase with the use of natural zeolite. However, the MCW with natural zeolite, the NH4(+)-N removal rate showed a direct relationship only with the NH4(+)-N influent concentration. Additionally, relationship between the oxygen, energy and area regarding the NH4(+)-N removal efficiency was established for 2.5-12.5 gO2/(kWh-m(2)) in the G-Line and 0.1-2.6 gO2/(kWh-m(2)) in the Z Line. Finally, it was established that a combination of natural zeolite as a support medium and the aeration strategy in a single CW could regenerate the zeolite's adsorption sites and maintain a given NH4(+)-N removal efficiency over time. PMID- 26848983 TI - Lignin-carbohydrate complexes from sisal (Agave sisalana) and abaca (Musa textilis): chemical composition and structural modifications during the isolation process. AB - MAIN CONCLUSION: Two types of lignins occurred in different lignin-carbohydrate fractions, a lignin enriched in syringyl units, less condensed, preferentially associated with xylans, and a lignin with more guaiacyl units, more condensed, associated with glucans. Lignin-carbohydrate complexes (LCC) were isolated from the fibers of sisal (Agave sisalana) and abaca (Musa textilis) according to a plant biomass fractionation procedure recently developed and which was termed as "universally" applicable to any type of lignocellulosic material. Two LCC fractions, namely glucan-lignin (GL) and xylan-lignin (XL), were isolated and differed in the content and composition of carbohydrates and lignin. In both cases, GL fractions were enriched in glucans and comparatively depleted in lignin, whereas XL fractions were depleted in glucans, but enriched in xylans and lignin. Analysis by two-dimensional Nuclear Magnetic Resonance (2D-NMR) and Derivatization Followed by Reductive Cleavage (DFRC) indicated that the XL fractions were enriched in syringyl (S)-lignin units and beta-O-4' alkyl-aryl ether linkages, whereas GL fractions have more guaiacyl (G)-lignin units and less beta-O-4' alkyl-aryl ether linkages per lignin unit. The data suggest that the structural characteristics of the lignin polymers are not homogeneously distributed within the same plant and that two different lignin polymers with different composition and structure might be present. The analyses also suggested that acetates from hemicelluloses and the acyl groups (acetates and p-coumarates) attached to the gamma-OH of the lignin side chains were extensively hydrolyzed and removed during the LCC fractionation process. Therefore, caution must be paid when using this fractionation approach for the structural characterization of plants with acylated hemicelluloses and lignins. Finally, several chemical linkages (phenylglycosides and benzyl ethers) could be observed to occur between lignin and xylans in these plants. PMID- 26848985 TI - Straighten the Back to Sit: Belly-Cultivation Techniques as "Modern Health Methods" in Japan, 1900-1945. AB - In Japan, the first half of the twentieth century saw a remarkable revival of concern with the cultivation of the belly, with a variety of belly-cultivation techniques, particularly breathing exercise and meditative sitting, widely practiced for improving health and treating diseases. This article carefully examines some practitioners' experiences of belly-cultivation practice in attempting to understand its healing effects for them within their life histories and contemporary intellectual, social and cultural contexts. It shows that belly cultivation practice served as a medium for some practitioners to reflect on and retell their life stories, and that the personal charisma of certain masters and the communities developing around them provided practitioners with a valuable sense of belonging in an increasingly industrialized and urbanized society. Moreover, these belly-cultivation techniques provided an embodied way for some to explore and affirm their sense of self and develop individual identity. While they were increasingly promoted as cultural traditions capable of cultivating national character, they also served as healing practices by inspiring practitioners with a sense of collective identity and purpose. With these analyses, this article sheds light on the complicated meanings of belly cultivation for practitioners, and provides illustrative examples of the multitude of meanings of the body, bodily cultivation and healing. PMID- 26848984 TI - A SCARECROW-based regulatory circuit controls Arabidopsis thaliana meristem size from the root endodermis. AB - MAIN CONCLUSION: SCARECROW controls Arabidopsis root meristem size from the root endodermis tissue by regulating the DELLA protein RGA that in turn mediates the regulation of ARR1 levels at the transition zone. Coherent organ growth requires a fine balance between cell division and cell differentiation. Intriguingly, plants continuously develop organs post-embryonically thanks to the activity of meristems that allow growth and environmental plasticity. In Arabidopsis thaliana, continued root growth is assured when division of the distal stem cell and their daughters is balanced with cell differentiation at the meristematic transition zone (TZ). We have previously shown that at the TZ, the cytokinin dependent transcription factor ARR1 controls the rate of differentiation commitment of meristematic cells and that its activities are coordinated with those of the distal stem cells by the gene SCARECROW (SCR). In the stem cell organizer (the quiescent center, QC), SCR directly suppresses ARR1 both sustaining stem cell activities and titrating non-autonomously the ARR1 transcript levels at the TZ via auxin. Here, we show that SCR also exerts a fine control on ARR1 levels at the TZ from the endodermis by sustaining gibberellin signals. From the endodermis, SCR controls the RGA REPRESSOR OF ga1-3 (RGA) DELLA protein stability throughout the root meristem, thus controlling ARR1 transcriptional activation at the TZ. This guarantees robustness and fineness to the control of ARR1 levels necessary to balance cell division to cell differentiation in sustaining coherent root growth. Therefore, this work advances the state of the art in the field of root meristem development by integrating the activity of three hormones, auxin, gibberellin, and cytokinin, under the control of different tissue-specific activities of a single root key regulator, SCR. PMID- 26848986 TI - The Tyrosine Kinase Pyk2 Contributes to Complement-Mediated Phagocytosis in Murine Macrophages. AB - Proline-rich tyrosine kinase 2 (Pyk2) is a member of the focal adhesion kinase (FAK) family and is mainly expressed in neuronal and hematopoietic cells. As FAK family members are involved in signaling connections downstream of integrins, we studied the role of Pyk2 in complement-receptor 3 (CR3, also known as Mac-1, integrin alphaMbeta2, CD11b/CD18)-mediated phagocytosis, a key process in innate immunity. Using 3 independent approaches, we observed that Pyk2 contributes to CR3-dependent phagocytosis by RAW 264.7 macrophages, but is dispensable for Fcgamma receptor (FcgammaR)-mediated uptake. Reduction of Pyk2 expression levels via siRNA, the pharmacological inhibition of Pyk2 kinase activity as well as macrophage treatment with a cell permeable TAT fusion protein containing the C terminus of Pyk2 (TAT-PRNK) significantly impaired CR3-mediated phagocytosis without affecting FcgammaR-mediated uptake. In addition, Pyk2 was strongly recruited to complement opsonized Escherichia coli and the pharmacological inhibition of Pyk2 significantly decreased uptake of the bacteria. Finally, CRISPR/Cas-mediated disruption of the pyk2 gene in RAW 264.7 macrophages confirmed the role of this protein tyrosine kinase in CR3-mediated phagocytosis. Together, our data demonstrate that Pyk2 selectively contributes to the coordination of phagocytosis-promoting signals downstream of CR3, but is dispensable for FcgammaR-mediated phagocytosis. PMID- 26848987 TI - Dialysis-Related Acidemia and Acidosis by Dialysate: The Forgotten Issue of CO2 Overload from Dialysate. PMID- 26848989 TI - Short and Scalable Total Synthesis of Myrioneuron Alkaloids (+/-)-alpha,beta Myrifabral A and B. AB - The first total synthesis of the Myrioneuron alkaloids (+/-)-alpha,beta myrifabral A and B has been accomplished in only four steps from conveniently available starting materials. This short synthesis relied on the use of a key tandem Mannich/amidation reaction to rapidly construct the core framework and two carbon stereocenters. The synthetic route allows for large scale preparation of these promising natural products against the hepatitis C virus (HCV). PMID- 26848988 TI - Dramatic Domain Rearrangements of the Cyanobacterial Orange Carotenoid Protein upon Photoactivation. AB - Photosynthetic cyanobacteria make important contributions to global carbon and nitrogen budgets. A protein known as the orange carotenoid protein (OCP) protects the photosynthetic apparatus from damage by dissipating excess energy absorbed by the phycobilisome, the major light-harvesting complex in many cyanobacteria. OCP binds one carotenoid pigment, but the color of this pigment depends on conditions. It is orange in the dark and red when exposed to light. We modified the orange and red forms of OCP by using isotopically coded cross-linking agents and then analyzed the structural features by using liquid chromatography and tandem mass spectrometry. Unequivocal cross-linking pairs uniquely detected in red OCP indicate that, upon photoactivation, the OCP N-terminal domain (NTD) and C-terminal domain (CTD) reorient relative to each other. Our data also indicate that the intrinsically unstructured loop connecting the NTD and CTD not only is involved in the interaction between the two domains in orange OCP but also, together with the N-terminal extension, provides a structural buffer system facilitating an intramolecular breathing motion of the OCP, thus helping conversion back and forth from the orange to red form during the OCP photocycle. These results have important implications for understanding the molecular mechanism of action of cyanobacterial photoprotection. PMID- 26848990 TI - Biochip-Based Genotyping Assay for Detection of Polymorphisms in Pigmentation Genes Associated with Cutaneous Melanoma. AB - AIMS: The purpose of the study was to develop a new assay for genotyping nine single nucleotide polymorphisms (SNPs) that are known to be associated with melanoma. METHODS: Two-stage single tube polymerase chain reaction (PCR) followed by hybridization on a biochip was developed and applied in the study. RESULTS: A total of nine SNPs were selected from five genes: MC1R (rs1805006, rs1805007, rs1805009, rs11547464), HERC2 (rs12913832), OCA2 (rs1800407), SLC45A2 (rs16891982), TYR (rs1393350), and a SNP from the intergenic locus rs12896399 were used for the synthesis of ssDNAs via a single-stage PCR process. The assays were performed on a biochip-based platform that is capable of SNP genotyping via a single reaction-tube PCR, followed by on chip hybridization. We tested 69 DNAs obtained from healthy persons and demonstrated the assays' ability to discriminate all three genotypes for almost all of the SNPs. CONCLUSIONS: The developed approach proved robust, suggesting that it might be useful for the personalized genotyping of large cohorts of patients. PMID- 26848991 TI - Dysfunction of WNT4/WNT5A in deciduas: possible relevance to the pathogenesis of preeclampsia. AB - OBJECTIVES: Preeclampsia affects 5-7% of all human pregnancies worldwide. It is characterized primarily by hypertension and proteinuria. Although the pathogenesis of preeclampsia is still not fully understood, the deficiency in decidualization is considered to have a role in this disease. WNT4 and WNT5A are highly expressed in the deciduas of mice and human beings; their deficiency causes the abnormality of mouse decidualization, and consequently affects the development of the placenta and the fetus. We aimed to define the roles of WNT4 and WNT5A in human decidulization and their relationship with preeclampsia. METHODS: In this study, we investigated the expression of WNT4 and WNT5A in human deciduas and their functions during decidualization, as well as their relationship with preeclampsia. We obtained deciduas from 20 women whose pregnancies were complicated by severe preeclampsia and from 20 women with uncomplicated pregnancies, as well as human endometrial stromal cells (hESCs). The levels of WNT4 and WNT5A were examined by real-time PCR, immunohistochemistry, and western blotting in deciduas. The expression of WNT4 and WNT5A in cultured hESCs was determined during decidualization. Furthermore, the roles of WNT4, WNT5A, and BMP2 on decidualization as well as their interactions were studied in cultured hESCs by interference of their expression with specific small interfering RNA, respectively. RESULTS: WNT4 and WNT5A were present in the decidual tissues of women with preeclampsia and women with uncomplicated pregnancies. Their expression levels of mRNA and protein in women with severe preeclampsia were significantly lower compared with women with uncomplicated pregnancies (P < 0.05). WNT4 and WNT5A were upregulated in decidualized hESCs. Knocking down of BMP2 or WNT4 in hESCs resulted in a significant increase of WNT5A mRNA and a significant reduction in the transcription of decidualization markers, insulin-like growth factor binding protein1 and prolactin (P < 0.05). In addition, silencing of WNT5A resulted in a reduction of the transcription of insulin-like growth factor binding protein1 and prolactin mRNA (P < 0.05). CONCLUSION: Our data suggest that WNT4 and WNT5 are relevant to normal decidualization, and thus trophoblast invasion and implantation. Their deficiency is likely involved in the development of preeclampsia. PMID- 26848992 TI - G protein-coupled receptor 30 regulates trophoblast invasion and its deficiency is associated with preeclampsia. AB - BACKGROUND: Preeclampsia is known to be associated with reduced circulating levels of estrogen. The effects of estrogen in preeclampsia are normally mediated by the classical estrogen receptors. Intriguingly, a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), has been recently found to play an important role in several estrogenic effects. However, the mechanisms by which GPR30 may mediate the development of preeclampsia remain unknown. METHOD: We observed that the expression of GPR30 in placental trophoblast cells is lower in preeclamptic placentas compared with normotensive controls. We then investigated the role of GPR30 in trophoblast cell invasion by utilizing placental explants and the immortalized human trophoblast cell line (HTR8/SVneo). RESULTS: The selective GPR30 agonist G1 and a general estrogen receptors agonist 17-beta-estradiol (E2) both improved trophoblast cells invasion by upregulating MMP9 expression and the PI3K-Akt signaling pathway. This effect was abolished by a selective GPR30 inhibitor G15, implying that GPR30 may be involved in regulating trophoblast invasion, and that down-regulation of this receptor may result in the development of preeclampsia. CONCLUSION: The present study suggests that GPR30 is a critical regulator of trophoblast cell invasion, and as such may be a potential therapeutic interventional target for preeclampsia and other pregnancy complications resulting from impaired trophoblast invasion. PMID- 26848993 TI - Short-term high salt intake reduces brachial artery and microvascular function in the absence of changes in blood pressure. AB - OBJECTIVES: The aims of this study were to test the hypothesis that short-term high salt intake reduces macrovascular and microvascular endothelial function in the absence of changes in blood pressure and to determine whether acute exercise restores endothelial function after high salt in women. MATERIALS AND METHODS: Twelve women were administered high salt (11 g of sodium chloride for 7 days) and then underwent a weightlifting session. Brachial artery flow-mediated dilation and nitroglycerin dilation were measured with ultrasound at baseline, after high salt, and after weightlifting. Subcutaneous fat tissue biopsies were obtained at baseline, after high salt, and after weightlifting. Resistance arteries from biopsies were cannulated for vascular reactivity measurements in response to flow [flow-induced dilation (FID)] and acetylcholine. RESULTS: Blood pressure was similar before and after high salt diet. Brachial flow-mediated dilation was reduced after high salt diet but was not affected by acute weightlifting. Brachial nitroglycerin dilations were similar before and after high salt. FID and acetylcholine-induced dilation of resistance arteries were similar to that of before and after high salt diet. FID and acetylcholine-induced dilation was not altered by weightlifting after high salt diet. However, N-nitro-L-arginine methyl ester significantly reduced FID at baseline and after exercise but had no effect dilator reactivity after high salt diet alone. CONCLUSION: These data suggest that high salt intake reduces brachial artery endothelial function and switches the mediator of vasodilation in the microcirculation to a non-nitric oxide dependent mechanism in healthy adults and acute exercise may switch the dilator mechanism back to nitric oxide during high salt diet. PMID- 26848994 TI - Effects of blood pressure lowering on outcome incidence in hypertension: 7. Effects of more vs. less intensive blood pressure lowering and different achieved blood pressure levels - updated overview and meta-analyses of randomized trials. AB - BACKGROUND AND OBJECTIVES: Previous meta-analyses of our group have investigated the cardiovascular effects of more vs. less intense blood pressure (BP) treatment and the BP levels to be achieved by treatment. A few additional trials have been completed recently, particularly the large SPRINT study. Updating of the previous meta-analyses has been done with the objective of further clarifying the practical question of BP targets of antihypertensive treatment. METHODS: Among randomized-controlled trials (RCTs) of BP lowering treatment between 1966 and 2015, 16 (52 235 patients) compared more vs. less intense treatment and fulfilled other preset criteria, and in 34 (138 127 patients) SBP in the active (vs. placebo) or the more (vs. less) intense treatment was below (vs., respectively, above) three predetermined cutoffs. For their meta-analyses risk ratios (RR) and 95% confidence intervals, standardized to -10/-5 mmHg SBP/DBP reduction, and absolute risk reductions of seven fatal and nonfatal outcomes were calculated. RESULTS: More intense BP lowering significantly reduced risk of stroke [RR 0.71 (0.60-0.84)], coronary events [0.80 (0.68-0.95)], major cardiovascular events [0.75 (0.68-0.85)] and cardiovascular mortality [0.79 (0.63-0.97)], but not heart failure and all-cause death. When the 16 RCTs were stratified according to cardiovascular death risk, relative risk reduction did not differ between strata, but absolute risk reduction increased with cardiovascular risk, though the residual risk also increased. Stratification of the 34 RCTs according to the three different SBP cutoffs (150, 140 and 130 mmHg) showed that a SBP/DBP difference of -10/-5 mmHg across each cutoff significantly reduced risk of all outcomes to the same proportion (relative risk reduction), but absolute risk reduction of most outcomes had a significant trend to decrease at lower cutoffs. CONCLUSION: Updating of previous meta-analyses indicates that more vs. less intense BP lowering can reduce not only stroke and coronary events, but also cardiovascular mortality. Including data from recent RCTs also shows that all major outcomes can be reduced by lowering SBP a few mmHg below vs. above 130 mmHg, but absolute risk reduction becomes smaller, suggesting patients at lower initial SBP were at a lower level of cardiovascular risk. PMID- 26848995 TI - Kinetic Control of Rh(III)-Catalyzed Annulation of C-H Bonds with Quinones: Chemoselective Synthesis of Hydrophenanthridinones and Phenanthridinones. AB - A temperature-dependent redox-neutral Rh(III)-catalyzed C-H bond annulation of N methoxybenzamides with quinones was developed for the chemoselective synthesis of hydrophenanthridinones and phenanthridinones. This reaction involves an Rh(III) catalyzed C-H bond functionalization and a subsequent cyclization through the directing group nucleophilic addition to the carbonyl group at room temperature. PMID- 26848996 TI - The other-race effect in face learning: Using naturalistic images to investigate face ethnicity effects in a learning paradigm. AB - The other-race effect in face identification has been reported in many situations and by many different ethnicities, yet it remains poorly understood. One reason for this lack of clarity may be a limitation in the methodologies that have been used to test it. Experiments typically use an old-new recognition task to demonstrate the existence of the other-race effect, but such tasks are susceptible to different social and perceptual influences, particularly in terms of the extent to which all faces are equally individuated at study. In this paper we report an experiment in which we used a face learning methodology to measure the other-race effect. We obtained naturalistic photographs of Chinese and Caucasian individuals, which allowed us to test the ability of participants to generalize their learning to new ecologically valid exemplars of a face identity. We show a strong own-race advantage in face learning, such that participants required many fewer trials to learn names of own-race individuals than those of other-race individuals and were better able to identify learned own-race individuals in novel naturalistic stimuli. Since our methodology requires individuation of all faces, and generalization over large image changes, our finding of an other-race effect can be attributed to a specific deficit in the sensitivity of perceptual and memory processes to other-race faces. PMID- 26848997 TI - Reading changes in children and adolescents with dyslexia after transcranial direct current stimulation. AB - Noninvasive brain stimulation offers the possibility to induce changes in cortical excitability and it is an interesting option as a remediation tool for the treatment of developmental disorders. This study aimed to investigate the effect of transcranial direct current stimulation (tDCS) on reading and reading related skills of children and adolescents with dyslexia. Nineteen children and adolescents with dyslexia performed different reading and reading-related tasks (word, nonword, and text reading; lexical decision; phonemic blending; verbal working memory; rapid automatized naming) in a baseline condition without tDCS and after 20 min of exposure to three different tDCS conditions: left anodal/right cathodal tDCS to enhance left lateralization of the parietotemporal region, right anodal/left cathodal tDCS to enhance right lateralization of the parietotemporal region, and sham tDCS. In text reading, results showed a significant reduction in errors after left anodal/right cathodal tDCS and an increase in errors after left cathodal/right anodal tDCS. No effect was found in the other reading and reading-related tasks. Our findings indicate for the first time that one session of tDCS modulates some aspects of reading performance of children and adolescents with dyslexia and that the effect is polarity dependent. These single-session results support a potential role of tDCS for developing treatment protocols and suggest possible parameters for tDCS treatment customization in children and adolescents with dyslexia. PMID- 26848998 TI - Galectin-3 expression in hippocampal CA2 following transient forebrain ischemia and its inhibition by hypothermia or antiapoptotic agents. AB - Recent evidence has suggested that the hippocampal CA2 region plays an important role in the recognition process. We have reported that ischemic damage in the hippocampal CA2 region following transient ischemia is caused by apoptosis, but the underlying mechanisms are still not clear. Galectin-3 is a beta-galactosidase binding lectin that is important in cell proliferation and apoptotic regulation. We have also reported that galectin-3 was expressed in activated microglia in the CA1 region 96 h after transient ischemia. The aim of this study is to determine the localization and time course of galectin-3 expression in the CA2 region following transient forebrain ischemia. Galectin-3 immunostaining was observed in both interior side of CA1 region and CA2 region in hippocampus 60 h after ischemic insult. At 66 h, galectin-3 was observed in the whole CA1 region adjacent to the CA2 region in the hippocampus. Both galectin-3 expression and neuronal cell death in the CA2 region were significantly inhibited by hypothermia and by apoptosis-inhibiting reagents. These results suggest that galectin-3 in the CA2 region is expressed independent of that in the CA1 region. Protection of the expression of galectin-3 in the CA2 region might contribute toward the survival of CA2 pyramidal neurons. PMID- 26849000 TI - Spectrophotometric and visual evaluation of peri-implant soft tissue color. AB - AIM: To spectrophotometrically and visually test whether the peri-implant mucosal color differs from the color of the natural gingiva. MATERIAL AND METHODS: Forty single implants in the incisor and premolar region of 40 patients were assessed 3 7 years after implant placement. The differences of the color components lightness, chroma along red-green axis, chroma along yellow-blue axis, and the total color difference DeltaE between peri-implant mucosa and natural gingiva were measured with a spectrophotometer. The color difference between peri-implant mucosa and natural gingiva was visually evaluated by clinicians and rated as "clinically visible" or "clinically invisible" from speaking distance. The dimensions of peri-implant mucosa and gingiva at the mid-buccal aspect were evaluated by using cone-beam CT. Spearman analysis was performed to detect correlations between different variables. Two-sided t-test, ANOVA, Mann-Whitney, and Kruskal-Wallis tests were applied to detect differences between the groups. RESULTS: The spectrophotometrically assessed color difference DeltaE between peri implant mucosa and natural gingiva amounted to 7.0 +/- 3.9. The peri-implant mucosa presented a significant dark, greenish and bluish discoloration in comparison with gingiva at control teeth. Clinical investigation revealed that in 60% of sites the color difference between peri-implant mucosa and natural gingiva was clinically visible from speaking distance. The threshold value DeltaE for the extraoral clinical distinction of mucosal color differences measured 7.5. When comparing the groups with visible and invisible color differences with respect to the three color components, a significant difference was found only for chroma along yellow-blue axis. In the group with visible color difference, mucosa presented a bluish discoloration. Correlation analysis indicated that with an increase in mucosal thickness, a trend for smaller DeltaE was found. CONCLUSION: The spectrophotometrically assessed color of the peri-implant mucosa revealed more dark, green and blue components compared to the natural gingiva. At 60% of the implants, peri-implant mucosal discoloration was visible from speaking distance. The sites with visible and those with invisible mucosal discolorations differed significantly only regarding the chroma along yellow-blue axis. PMID- 26849001 TI - Flow cytometry as an improved method for the titration of Chlamydiaceae and other intracellular bacteria. AB - Chlamydiaceae is a family of intracellular bacteria causing a range of diverse pathological outcomes. The most devastating human diseases are ocular infections with C. trachomatis leading to blindness and genital infections causing pelvic inflammatory disease with long-term sequelae including infertility and chronic pelvic pain. In order to enable the comparison of experiments between laboratories investigating host-chlamydia interactions, the infectious titer has to be determined. Titer determination of chlamydia is most commonly performed via microscopy of host cells infected with a serial dilution of chlamydia. However, other methods including fluorescent ELISpot (Fluorospot) and DNA Chip Scanning Technology have also been proposed to enumerate chlamydia-infected cells. For viruses, flow cytometry has been suggested as a superior alternative to standard titration methods. In this study we compared the use of flow cytometry with microscopy and Fluorospot for the titration of C. suis as a representative of other intracellular bacteria. Titer determination via Fluorospot was unreliable, while titration via microscopy led to a linear read-out range of 16 - 64 dilutions and moderate reproducibility with acceptable standard deviations within and between investigators. In contrast, flow cytometry had a vast linear read-out range of 1,024 dilutions and the lowest standard deviations given a basic training in these methods. In addition, flow cytometry was faster and material costs were lower compared to microscopy. Flow cytometry offers a fast, cheap, precise, and reproducible alternative for the titration of intracellular bacteria like C. suis. (c) 2016 International Society for Advancement of Cytometry. PMID- 26849002 TI - Making the Case for Palliative Care at the System Level: Outcomes Data. AB - BACKGROUND: A recent trend in health care is to integrate palliative care (PC) programs across multiple hospitals to reduce variation, improve quality, and reduce cost. OBJECTIVE: The study objective was to demonstrate the benefits of PC for a system. METHODS: The study was a descriptive study using retrospective medical records in seven federated hospitals where PC developed differently before system integration. Measured were length of stay (LOS), mortality, readmissions, saved intensive care unit (ICU) days, cost avoidance, and hospice referrals. RESULTS: PC services within the first 48 hours of admission demonstrate a shorter LOS (5.08 days), reduced costs 40% ($2,362 per day), and decreased mortality (1.01 versus 1.10) for one hospital. Readmissions at 30, 60, and 90 days after a PC consult decreased (61.5%, 47.0%, and 42.1%, respectively). Annual pre- and postprogram referrals to hospice increased (65 to 107). Using modified matched pairs, LOS of PC patients seen within 48 hours of admission average 1.67 days less compared to non-PC patients. LOS for ICU patients with PC services in the ICU within the first 48 hours decreased by 1.12 days. Overall cost avoidance was 1.5 times total cost for PC programs systemwide. One pilot project using a full-time physician in the ICU reduced cost more than $600,000, with 315 saved ICU days, annualized. Systemwide, 69.3% of all referrals to hospice were made by the PC service. CONCLUSION: Early involvement of PC services emerged as advantageous to the net benefit. Given that health care's changing landscape will increasingly include bundled payment and risk holding strategies to improve quality and reduce cost in health care systems, systemwide PC will play a vital role. PMID- 26849003 TI - Next steps for adolescent and young adult oncology workshop: An update on progress and recommendations for the future. AB - Each year, 70,000 adolescents and young adults (AYAs) between ages 15 and 39 years in the United States are diagnosed with cancer. In 2006, a National Cancer Institute (NCI) Progress Review Group (PRG) examined the state of science associated with cancer among AYAs. To assess the impact of the PRG and examine the current state of AYA oncology research, the NCI, with support from the LIVESTRONG Foundation, sponsored a workshop entitled "Next Steps in Adolescent and Young Adult Oncology" on September 16 and 17, 2013, in Bethesda, Maryland. This report summarizes the findings from the workshop, opportunities to leverage existing data, and suggestions for future research priorities. Multidisciplinary teams that include basic scientists, epidemiologists, trialists, biostatisticians, clinicians, behavioral scientists, and health services researchers will be essential for future advances for AYAs with cancer. PMID- 26849004 TI - Persistent Luminescence Hole-Type Materials by Design: Transition-Metal-Doped Carbon Allotrope and Carbides. AB - Electron traps play a crucial role in a wide variety of compounds of persistent luminescence (PL) materials. However, little attention has been placed on the hole-trap-type PL materials. In this study, a novel hole-dominated persistent luminescence (PL) mechanism is predicted. The mechanism is validated in the night pearl diamond (NPD) composed of lonsdaleite with ultralong persistent luminescence (PL) (more than 72 h). The computed band structures suggest that the Fe ion dopant in lonsdaleite is responsible for the luminescence of NPD due to the desired defect levels within the band gap for electronic transition. Other possible impurity defects in lonsdaleite, such as K, Ca, Mg, Zn, or Tl dopants, or C vacancy can also serve as the hole-trap centers to enhance the PL. Among other 3d transition-metal-ion dopants considered, Cr and Mn ions are predicted to give rise to PL property. The predicted PL mechanism via transition-metal doping of lonsdaleite offers an exciting opportunity for engineering new PL materials by design. PMID- 26849005 TI - Lifetime Prevalence and Characteristics of Child Sexual Victimization in a Community Sample of Spanish Adolescents. AB - The purpose of this study was to investigate the lifetime prevalence and characteristics of self-reported child sexual victimization and associations between sexual victimization and sociodemographic characteristics and victimological profiles in community adolescents in Spain. The Juvenile Victimization Questionnaire (Finkelhor, Hamby, Ormrod, & Turner, 2005) was applied to a sample of 1,105 community adolescents (M = 14.52 years, SD = 1.76). Experience of sexual victimization (with or without physical contact) was reported by 8.8% of the sample, at a mean age of 13 years old. Sexual victimization was more prevalent in girls (14.2%) and in older adolescents (10.6%). Offenders were mainly male (87.6%) and were mostly friends, neighbors, or schoolmates (52.6%). No injuries resulted from victimization (4.3%), although the percentage of penetration or attempted penetration was very high (30.6%). Only 9.3% of victims reported the incident to the police or the justice system. In regard to victimological profiles, sexual victims also experienced other forms of victimization (M = 7.16; SD = 3.39): boys reported more conventional crimes, peer and sibling victimization, and witnessing community violence than other victims, whereas sexually victimized girls reported more caregiver victimization and property crimes. Sexually victimized youth present a distinctive sociodemographic and victimological profile. Professionals need to be aware of these characteristics in order to conduct adequate prevention programs. We also need to assess a wide range of victimization experiences when treating sexual abuse victims in order to make adolescents less vulnerable to violence. PMID- 26849007 TI - Sirolimus-Induced Diffuse Alveolar Hemorrhage: A Case Report. AB - Sirolimus is a mammalian target of the rapamycin, a protein kinase, which is responsible for inhibition of T cell and B cell proliferation. Sirolimus has side effects on lugs, and may cause cryptogenic organizing pneumonia, diffuse alveolar hemorrhage, lymphocytic pneumonitis, hypersensitivity pneumonitis, desquamative interstitial pneumonia, and pulmonary alveolar proteinosis. Diagnosis is based on the combination of clinical, radiological, histological, and pathological investigation. We report a case of diffuse alveolar hemorrhage in a 33-year-old, female renal transplant recipient. After discontinuation of sirolimus, radiological images and clinical condition of the patient got better. We also planned steroid therapy for 6 months by tapering the dosage slowly. After steroid therapy, full recovery of pulmonary functions achieved, and the patient is observed in our outpatient clinic with lack of any pulmonary symptoms. PMID- 26849006 TI - Renal dysplasia in the neonate. AB - PURPOSE OF REVIEW: Renal dysplasia is classically described as a developmental disorder whereby the kidneys fail to undergo appropriate differentiation, resulting in the presence of malformed renal tissue elements. It is the commonest cause of chronic kidney disease and renal failure in the neonate. Although several genes have been identified in association with renal dysplasia, the underlying molecular mechanisms are often complex and heterogeneous in nature, and remain poorly understood. RECENT FINDINGS: In this review, we describe new insights into the fundamental process of normal kidney development, and how the renal cortex and medulla are patterned appropriately during gestation. We review the key genes that are indispensable for this process, and discuss how patterning of the kidney is perturbed in the absence of these signaling pathways. The recent use of whole exome sequencing has identified genetic mutations in patients with renal dysplasia, and the results of these studies have increased our understanding of the pathophysiology of renal dysplasia. SUMMARY: At present, there are no specific treatments available for patients with renal dysplasia. Understanding the molecular mechanisms of normal kidney development and the pathogenesis of renal dysplasia may allow for improved therapeutic options for these patients. PMID- 26849008 TI - The cut-off value for interleukin 34 as an additional potential inflammatory biomarker for the prediction of the risk of diabetic complications. AB - In the present study, we have decided to evaluate whether serum interleukin 34 (IL-34) levels may have diagnostic value in predicting the risk of vascular diabetic complications. The study included 49 patients with type 2 diabetes mellitus (T2DM) and 23 high-risk group. The receiver operating characteristic (ROC) curve analysis has shown that IL-34 has more discriminatory power than C reactive protein (CRP) for the risk of diabetic complications. The cut-off value for IL-34 was established as 91.2 pg/mL. The gist of our research was identification of IL-34 as an additional potential inflammatory biomarker for the prediction of the risk of vascular diabetic complications. PMID- 26849009 TI - Rapid Computation of Thermodynamic Properties over Multidimensional Nonbonded Parameter Spaces Using Adaptive Multistate Reweighting. AB - We show how thermodynamic properties of molecular models can be computed over a large, multidimensional parameter space by combining multistate reweighting analysis with a linear basis function approach. This approach reduces the computational cost to estimate thermodynamic properties from molecular simulations for over 130,000 tested parameter combinations from over 1000 CPU years to tens of CPU days. This speed increase is achieved primarily by computing the potential energy as a linear combination of basis functions, computed from either modified simulation code or as the difference of energy between two reference states, which can be done without any simulation code modification. The thermodynamic properties are then estimated with the Multistate Bennett Acceptance Ratio (MBAR) as a function of multiple model parameters without the need to define a priori how the states are connected by a pathway. Instead, we adaptively sample a set of points in parameter space to create mutual configuration space overlap. The existence of regions of poor configuration space overlap are detected by analyzing the eigenvalues of the sampled states' overlap matrix. The configuration space overlap to sampled states is monitored alongside the mean and maximum uncertainty to determine convergence, as neither the uncertainty or the configuration space overlap alone is a sufficient metric of convergence. This adaptive sampling scheme is demonstrated by estimating with high precision the solvation free energies of charged particles of Lennard-Jones plus Coulomb functional form with charges between -2 and +2 and generally physical values of sigmaij and epsilonij in TIP3P water. We also compute entropy, enthalpy, and radial distribution functions of arbitrary unsampled parameter combinations using only the data from these sampled states and use the estimates of free energies over the entire space to examine the deviation of atomistic simulations from the Born approximation to the solvation free energy. PMID- 26849010 TI - In vitro evaluation of metal chelators as potential metallo- beta -lactamase inhibitors. AB - AIMS: This study aimed at investigating the use of metal chelators as potential metallo-beta-lactamase inhibitors (MBL). METHODS AND RESULTS: The minimum inhibitory concentration (MIC) of meropenem was ascertained alone and in combination with various concentrations of macrocyclic (1,4,7- triazacyclononane 1-glutaric acid-4,7-diacetic acid = NODAGA) peptide derivatives and acyclic (N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine = TPEN and di-(2 picolyl)amine = DPA) metal chelators using the broth microdilution method. MICs of meropenem against carbapenem-resistant enterobacteriaceae (CRE) producing MBLs were decreased to concentrations as low as 0.06 mg l(-1) in the presence of some metal chelators. TPEN at 4 and 8 mg l(-1) showed the best activity by decreasing meropenem MICs to 0.5 and 0.06 mg l(-1) , respectively, for some New Delhi Metallo-beta-lactamase (NDM) and Verona integron-encoded metallo-beta-lactamase (VIM) -producing enterobacteriaceae. DPA at 8 and 16 mg l(-1) was also able to decrease meropenem MICs to 1 and 0.125 mg l(-1) , respectively, for these CREs. NODAGA peptide derivatives showed the least inhibition as 32 mg l(-1) was required for meropenem MICs to be decreased to 0.06 mg l(-1) against an NDM-1 producing isolate. CONCLUSION: The various metal chelators, TPEN, DPA and NODAGA peptide derivatives were able to inhibit the MBLs in decreasing order of activity, rendering CREs susceptible to meropenem. SIGNIFICANCE AND IMPACT OF THE STUDY: In the absence of new antibiotics, this study evaluated metal chelators as potential MBL inhibitors. PMID- 26849012 TI - Waldenstrom macroglobulinemia: prognosis and management. PMID- 26849011 TI - Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life. AB - We evaluated temporal trends in survival of Swedish acute myeloid leukemia (AML) patients diagnosed between 1973 and 2011 using relative survival ratios (RSRs) and a measure called the loss in expectation of life (LEL). RSRs increased most for patients <60 years at diagnosis during the first calendar periods, but between 1997-2005 and 2006-2011 the most pronounced increase was for those aged 61-70 years at diagnosis; RSR changed from 0.16 (95% confidence interval (CI): 0.13-0.19) to 0.28 (95% CI: 0.23-0.33), respectively. The LEL for males aged 35 years at diagnosis was 41.0 (95% CI: 40.1-41.8) years in 1975 and 19.5 (95% CI: 16.4-22.5) years in 2011. For males aged 65 years, the corresponding figures were 13.8 (95% CI: 13.7-14.0) and 12.0 (95% CI: 11.3-12.8). Conditional LEL estimates suggested that patients who survive 5 years postdiagnosis have shorter remaining lifespan than the general population. The proportion of expected life lost (PELL) suggested that male 65-year-old patients lost 75% of their life expectancy in 2005 and 66% if they were diagnosed in 2011. Survival continued to increase to 2011, with larger improvements in those aged 61-70 years at diagnosis. The LEL and PELL are intuitive measures that may be useful in communicating survival statistics to patients, clinicians and health-care providers. PMID- 26849013 TI - Genetic basis of myeloid transformation in familial platelet disorder/acute myeloid leukemia patients with haploinsufficient RUNX1 allele. PMID- 26849015 TI - Thyroid Hormones and Timing of Pubertal Onset in a Longitudinal Cohort of Females, Northern California, 2006-11. AB - BACKGROUND: Pubertal timing is regulated by a complex interplay of hormones. Few studies have evaluated the role of thyroid hormones in pubertal onset. We investigated the associations between blood concentrations of free and total thyroxine (FT4, TT4), free triiodothyronine, and thyroid stimulating hormone and pubertal onset among females. METHODS: Participants included 323 Kaiser Permanente Northern California members followed at annual intervals during 2004 11, who provided a blood sample during the first 3 years of the study. Thyroid hormone concentrations were measured in serum in the first blood specimen available for each participant. Pubertal onset was defined as Tanner stage >=2 for breast (thelarche) and pubic hair (pubarche) development. Associations between thyroid hormones and pubertal onset were assessed by multivariable logistic regression and Cox proportional hazards modelling. RESULTS: At blood draw, participants were age 6.5-10.1 (median 7.7) years, 10% had reached thelarche, and 12% had reached pubarche. Participants were followed 0-5 years after blood draw (median 4). At most recent clinical visit, participants were age 6.7-14.7 (median 12.3) years, 92% had reached thelarche, and 89% had reached pubarche. No associations were identified between having reached thelarche or pubarche at time of blood draw and thyroid hormones. Examined longitudinally, higher concentrations of pre-pubertal FT4 and TT4 were associated with earlier pubarche (adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.06, 1.86; per ng/dL and aHR 1.07, 95% CI 1.02, 1.12; per MUg/dL respectively). CONCLUSIONS: Higher pre-pubertal concentrations of FT4 and TT4 are associated with earlier pubarche. PMID- 26849017 TI - The effect of age and increasing head-up tilt on pre-oxygenation times in children: a randomised exploratory study. AB - We conducted a randomised exploratory trial in children aged between one and sixteen years old to establish the time to achieve an end-tidal oxygen fraction >= 0.9 in three different positions: supine, and 30 and 45 degrees head up. We recruited 120 children analysed in two age groups: 1-8 years and 9-16 years. The median (IQR [range]) time to reach the end point was 80 (59-114 [41-295]) s in the younger group and 150 (107-211 [44-405]) s in the older group, regardless of position (p = 0.0001). The end point was reached in 90% of children in approximately 160 s in the younger, and 271 s in the older, groups, respectively. There was no statistical difference between the three positions within each age group in the time to reach the endpoint (p = 0.59). Only two patients in the older age group could not reach the end point, due to poorly fitting facemasks. We conclude that pre-oxygenation can therefore be achieved effectively in most children, and that tilting children head up by 30 or 45 degrees does not significantly reduce the time taken to achieve an end-tidal oxygen fraction of >= 0.9. The recommended period for pre-oxygenation in both groups should remain at 3 min but it should be noted that this may be insufficient for many older patients. PMID- 26849014 TI - Cytogenetic and molecular abnormalities in chronic myelomonocytic leukemia. AB - Chronic myelomonocytic leukemia (CMML) is a clonal stem cell disorder associated with peripheral blood monocytosis and an inherent tendency to transform to acute myeloid leukemia. CMML has overlapping features of myelodysplastic syndromes and myeloproliferative neoplasms. Clonal cytogenetic changes are seen in ~30%, whereas gene mutations are seen in >90% of patients. Common cytogenetic abnormalities include; trisomy 8, -Y, -7/del(7q), trisomy 21 and del(20q), with the Mayo-French risk stratification effectively risk stratifying patients based on cytogenetic abnormalities. Gene mutations frequently involve epigenetic regulators (TET2 ~60%), modulators of chromatin (ASXL1 ~40%), spliceosome components (SRSF2 ~50%), transcription factors (RUNX1 ~15%) and signal pathways (RAS ~30%, CBL ~15%). Of these, thus far, only nonsense and frameshift ASXL1 mutations have been shown to negatively impact overall survival. This has resulted in the development of contemporary, molecularly integrated (inclusive of ASXL1 mutations) CMML prognostic models, including Molecular Mayo Model and the Groupe Francais des Myelodysplasies model. Better understanding of the prevalent genetic and epigenetic dysregulation has resulted in emerging targeted treatment options for some patients. The development of an integrated (cytogenetic and molecular) prognostic model along with CMML-specific response assessment criteria are much needed future goals. PMID- 26849016 TI - Temporal course and predictive factors of analgesic opioid requirement for chemoradiation-induced oral mucositis in oropharyngeal cancer. AB - BACKGROUND: Oral mucositis (OM)-related pain affects most patients with head and neck cancer during treatments, but its management is not standardized. METHODS: We retrospectively collected data about the opioid therapy used for OM-induced pain in all patients with oropharyngeal cancer treated with chemoradiotherapy (CRT) between 2009 and 2013. To compare the different opioids, a conversion into oral morphine equivalent daily dose (OMEDD) was performed. The highest OMEDD (h OMEDD) and the opioids' weekly increase were associated with patient, tumor, or treatment-related characteristics in order to identify predictive factors of opioid consumption. RESULTS: Ninety-seven percent of patients received opioids. The h-OMEDD was significantly correlated with a higher OM-grade and a lower smoking history. The weekly opioids' increase was higher in patients with lower smoking history and human papillomavirus (HPV) positivity. CONCLUSION: Opioid therapy remains the mainstay for OM-related pain management during CRT. The role of previous smoking and HPV on opioid use needs further confirmations. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1521-E1527, 2016. PMID- 26849019 TI - Plasmonic Metallurgy Enabled by DNA. AB - Mixed silver and gold plasmonic nanoparticle architectures are synthesized using DNA-programmable assembly, unveiling exquisitely tunable optical properties that are predicted and explained both by effective thin-film models and explicit electrodynamic simulations. These data demonstrate that the manner and ratio with which multiple metallic components are arranged can greatly alter optical properties, including tunable color and asymmetric reflectivity behavior of relevance for thin-film applications. PMID- 26849021 TI - Expression of type 2 diacylglycerol acyltransferse gene DGTT1 from Chlamydomonas reinhardtii enhances lipid production in Scenedesmus obliquus. AB - Microalgal strains of Scenedesmus obliquus have the great potential for the production of biofuels, CO2 fixation, and bioremediation. However, metabolic engineering of S. obliquus to improve their useful phenotypes are still not fully developed. In this study, S. obliquus strain CPC2 was genetically engineered to promote the autotrophic growth and lipid productivity. The overexpression plasmid containing the type 2 diacylglycerol acyltransferse (DGAT) gene DGTT1 from Chlamydomonas reinhardtii was constructed and transformed into S. obliquus CPC2, and the positive transformants were obtained. The expression of DGTT1 gene was confirmed by reverse transcription PCR analysis. Enhanced lipid content of the transformant S. obliquus CPC2-G1 by nearly two-fold was observed. The biomass concentration of the recombinant strains was also 29% higher than that of the wild-type strain. Furthermore, the recombinant strain CPC2-G1 was successfully grown in 40 L tubular type photobioreactor and open pond system in an outdoor environment. The lipid content, biomass concentration, and biomass productivity obtained from 40 L tubular PBR were 127.8% 20.0%, and 232.6% higher than those obtained from the wild-type strain. The major aim of this work is to develop a tool to genetically engineer an isolated S. obliquus strain for the desired purpose. This is the first report that genetic engineering of S. obliquus has been successful employed to improve both the microalgal cell growth and the lipid production. PMID- 26849022 TI - Experimental Philosophy of Explanation Rising: The Case for a Plurality of Concepts of Explanation. AB - This paper brings together results from the philosophy and the psychology of explanation to argue that there are multiple concepts of explanation in human psychology. Specifically, it is shown that pluralism about explanation coheres with the multiplicity of models of explanation available in the philosophy of science, and it is supported by evidence from the psychology of explanatory judgment. Focusing on the case of a norm of explanatory power, the paper concludes by responding to the worry that if there is a plurality of concepts of explanation, one will not be able to normatively evaluate what counts as good explanation. PMID- 26849023 TI - Attentional gain and processing capacity limits predict the propensity to neglect unexpected visual stimuli. AB - Exogenous allocation of attentional resources allows the visual system to encode and maintain representations of stimuli in visual working memory (VWM). However, limits in the processing capacity to allocate resources can prevent unexpected visual stimuli from gaining access to VWM and thereby to consciousness. Using a novel approach to create unbiased stimuli of increasing saliency, we investigated visual processing during a visual search task in individuals who show a high or low propensity to neglect unexpected stimuli. When propensity to inattention is high, ERP recordings show a diminished amplification concomitantly with a decrease in theta band power during the N1 latency, followed by a poor target enhancement during the N2 latency. Furthermore, a later modulation in the P3 latency was also found in individuals showing propensity to visual neglect, suggesting that more effort is required for conscious maintenance of visual information in VWM. Effects during early stages of processing (N80 and P1) were also observed suggesting that sensitivity to contrasts and medium-to-high spatial frequencies may be modulated by low-level saliency (albeit no statistical group differences were found). In accordance with the Global Workplace Model, our data indicate that a lack of resources in low-level processors and visual attention may be responsible for the failure to "ignite" a state of high-level activity spread across several brain areas that is necessary for stimuli to access awareness. These findings may aid in the development of diagnostic tests and intervention to detect/reduce inattention propensity to visual neglect of unexpected stimuli. PMID- 26849024 TI - Micro-Computed Tomography of Tooth Volume Changes Following Post Removal. AB - PURPOSE: To measure tooth volume change before and after post removal using micro CT and to compare the difference among various combinations of prefabricated post and cement systems. MATERIALS AND METHODS: Forty-eight extracted maxillary anterior teeth and mandibular canines were sectioned 13 mm from the apex. Root canals were properly instrumented. Preparations were filled with gutta percha using lateral condensation. Post space was prepared with a touch and heat device, leaving 5 mm of gutta percha from the apex. Specimens were scanned with micro-CT to establish objective baseline volume and divided into two groups of post systems: stainless steel (SS) ParaPost and glass-fiber reinforced composite (FRC) post. Half the posts for each group were cemented with Ketac Cem radiopaque glass ionomer cement, and the other half with SpeedCEM dual-curing resin cement. The posts and residual cement were removed by the same operator, using the ultrasonic vibration technique under an endodontic operating microscope. The remaining tooth root structure was scanned again using micro-CT with volume reported (mm3 ). The statistical difference between the combination of posts and cements was measured using the Kruskal-Wallis ANOVA test (alpha = 0.001). The independent variables were evaluated separately using post hoc Tukey examination to determine which groups resulted in a statistically significant difference. RESULTS: There was a statistical difference of tooth root volume change among the groups. Post hoc exam revealed a statistically significant difference in tooth root volume change between group 1 (SS + GI) and the other groups (alpha = 0.0002). CONCLUSION: Compared to other post and cement combinations, serrated parallel-sided SS posts cemented with GI cement had the most tooth root structure loss upon post removal using the ultrasonic vibration technique. PMID- 26849025 TI - Bile ductal injury and ductular reaction are frequent phenomena with different significance in autoimmune hepatitis. AB - BACKGROUND & AIMS: The significance of bile duct injury and ductular reaction in biopsies from autoimmune hepatitis patients is not clear. We aim to establish the prevalence and clinical relevance of both phenomena in autoimmune hepatitis. METHODS: Cases of newly diagnosed, untreated autoimmune hepatitis without overlap syndrome were selected. Pretreatment and follow up biopsies were scored for inflammation, fibrosis, bile ductal injury and ductular reaction. RESULTS: Thirty five cases were studied of whom 14 cases had follow up biopsies. Bile duct injury was present in 29 cases (83%), mostly in a PBC-like pattern and was not correlated with demographical or laboratory findings. Ductular reaction, observed in 25 of 35 cases (71%) using conventional histology and in 30 of 32 cases (94%) using immunohistochemistry, was correlated with portal and lobular inflammation, interface hepatitis and centrilobular necrosis as well as bile duct injury and fibrosis. In 11 of 14 cases (79%) ductular reaction remained present on post treatment biopsy whereas bile duct injury persisted in six of 14 (43%) of cases. CONCLUSIONS: Bile duct injury and ductular reaction are very common in newly diagnosed autoimmune hepatitis and cannot be predicted biochemically. Bile duct injury may subside in the majority of treated AIH cases while DR tends to persist during follow up. These findings show that the two phenomena are part of the spectrum of AIH with dissimilar responses to treatment and do not necessarily point towards an overlap syndrome. Persistence of ductular reaction after treatment supports the notion that it represents a regenerative response. PMID- 26849026 TI - sDFIRE: Sequence-specific statistical energy function for protein structure prediction by decoy selections. AB - An important unsolved problem in molecular and structural biology is the protein folding and structure prediction problem. One major bottleneck for solving this is the lack of an accurate energy to discriminate near-native conformations against other possible conformations. Here we have developed sDFIRE energy function, which is an optimized linear combination of DFIRE (the Distance-scaled Finite Ideal gas Reference state based Energy), the orientation dependent (polar polar and polar-nonpolar) statistical potentials, and the matching scores between predicted and model structural properties including predicted main-chain torsion angles and solvent accessible surface area. The weights for these scoring terms are optimized by three widely used decoy sets consisting of a total of 134 proteins. Independent tests on CASP8 and CASP9 decoy sets indicate that sDFIRE outperforms other state-of-the-art energy functions in selecting near native structures and in the Pearson's correlation coefficient between the energy score and structural accuracy of the model (measured by TM-score). PMID- 26849027 TI - Indentation hardness: A simple test that correlates with the dissipated-energy predictor for fatigue-life in bovine pericardium membranes for bioprosthetic heart valves. AB - The aim of this study was to evaluate the variation of hardness with fatigue in calf pericardium, a biomaterial commonly used in bioprosthetic heart valves, and its relationship with the energy dissipated during the first fatigue cycle that has been shown to be a predictor of fatigue-life (Garcia Paez et al., 2006, 2007; Rojo et al., 2010). Fatigue tests were performed in vitro on 24 pericardium specimens cut in a root-to-apex direction. The specimens were subjected to a maximum stress of 1MPa in blocks of 10, 25, 50, 100, 250, 500, 1000 and 1500 cycles. By means of a modified Shore A hardness test procedure, the hardness of the specimen was measured before and after fatigue tests. Results showed a significant correlation of such hardness with fatigue performance and with the energy dissipated in the first cycle of fatigue, a predictor of pericardium durability. The study showed indentation hardness as a simple and reliable indicator of mechanical performance, one which could be easily implemented in improving tissue selection. PMID- 26849028 TI - Investigation of the fatigue behavior of adhesive bonding of the lithium disilicate glass ceramic with three resin cements using rotating fatigue method. AB - OBJECTIVE: To investigate the fatigue behavior of bonding interface of lithium disilicate ceramic with three different dual cure resin cements. MATERIAL AND METHODS: Forty five bar shaped ceramic-resin-ceramic specimens were prepared and divided into 3 groups (n=15) according to the resin cement used (group1: Panavia F2.0, group 2: RelyX Ultimate, group 3: Duo-Link Universal). Three specimens of each group were tested using three point bending test and the fracture strength of the resin-ceramic bond was measured. Other specimens of each group were placed in the rotating fatigue testing machine at stresses equal to 30%, 40%, 50% and 60% of the fracture strength. The cyclic loading was continued until fracture or a maximum of 10,000 cycles. For the specimens which did not fail until 10,000 cycles, the cyclic loading was stopped and the remained fracture strength of the specimens was measured. RESULTS: None of the specimens with cyclic loads of 30% and 40% of the fracture strength, have failed until 10,000 cycles. After 10,000 load cycles, the fracture strength of these specimens was significantly lower than their initial fracture strength. On the other hand, all specimens with cyclic stresses equal to 50% and 60% of the fracture strength have failed before 10,000 cycles so that the numbers of load cycles of RelyX specimens were significantly higher than those of Panavia ones and the numbers of cycles of Panavia specimens were significantly higher than those of Duo-Link specimens. CONCLUSION: The fatigue resistance of the ceramic-resin interface is significantly lower than its bond strength. Furthermore, RelyX Ultimate showed the highest fatigue resistance and Duo-Link Universal exhibited the weakest fatigue resistance. Since dental restorations are under cyclic loading caused by mastication forces, the results of this research can be used to select fatigue resistant resin cements for bonding of ceramic restorations. PMID- 26849029 TI - Failure analysis of retrieved PE-UHMW acetabular liners. AB - Ultra-high molecular weight polyethylene (PE-UHMW) acetabular liners have a limited lifespan in a patient's body. There are many factors affecting the performance of the implant and furthermore the properties of the polymeric material are changing after implantation. In this work material changes according to structure and morphology and their implication on mechanical properties are in focus. The physical and mechanical properties of ten crosslinked (xL) PE-UHMW and nine conventional (conv) gamma-sterilized PE-UHMW hip components, used as sliding surface in total hip joint replacement, with different in-vivo times are compared. The evaluation of the retrieved acetabular liners is performed in view of crosslinking and conventional gamma-sterilization but also in terms of the influence of gender concerning alteration in properties. The oxidative degradation in the PE-UHMW is investigated by means of Fourier Transformed Infrared Spectroscopy (FTIR). The characterization of the morphology is carried out via differential scanning calorimetry (DSC). A depth profile of the micro hardness and elastic modulus is taken over the cross-section of the components in order to find the influence of chemical constitution and morphology on the micro mechanical properties. It could be shown that crosslinking and oxidative degradation influence the degree of crystallinity of the polymer. Oxidation occurs for both types of the material due to in-vivo time. Higher degree of crystallinity can be correlated to higher hardness and indentation modulus. No unequivocal superiority of crosslinked over conventional liners can be observed. The influence of sex concerning alteration of the evaluated properties matters but need to be further investigated. PMID- 26849031 TI - Bioinspired polydimethylsiloxane-based composites with high shear resistance against wet tissue. AB - Patterned microstructures represent a potential approach for improving current wound closure strategies. Microstructures can be fabricated by multiple techniques including replica molding of soft polymer-based materials. However, polymeric microstructures often lack the required shear resistance with tissue needed for wound closure. In this work, scalable microstructures made from composites based on polydimethylsiloxane (PDMS) were explored to enhance the shear resistance with wet tissue. To achieve suitable mechanical properties, PDMS was reinforced by incorporation of polyethylene (PE) particles into the pre polymer and by coating PE particle reinforced substrates with parylene. The reinforced microstructures showed a 6-fold enhancement, the coated structures even a 13-fold enhancement in Young's modulus over pure PDMS. Shear tests of mushroom-shaped microstructures (diameter 450um, length 1mm) against chicken muscle tissue demonstrate first correlations that will be useful for future design of wound closure or stabilization implants. PMID- 26849030 TI - Loading frequencies up to 20Hz as an alternative to accelerate fatigue strength tests in a Y-TZP ceramic. AB - Considering the interest of the research community in the fatigue behavior of all ceramic restorations and the time consumed in low-frequency cyclic fatigue tests, this study aimed to investigate the influence of the loading frequency on the zirconia fatigue strength. The biaxial flexural fatigue strength of Y-TZP discs was determined by the staircase approach after 500,000 cycles. The investigated frequencies were 2Hz (control-simulation of the chewing activity; n=20), 10Hz (n=20), 20Hz (n=20), and 40Hz (n=21). The fatigue strength data were analyzed using one-way ANOVA and post-hoc Tukey's test (alpha=0.05). Pearson coefficient (r) was calculated to assess the existence of a correlation between fatigue strength and loading frequency. X-ray diffraction analysis was used to determine the relative amount of monoclinic phase under each fatigue test condition. The fatigue strength was significantly higher for 40Hz group (630.7+/-62.1MPa) and did not differ among the groups 2Hz (550.3+/-89.7MPa), 10Hz (574.0+/-47MPa) and 20Hz (605.1+/-30.7MPa). Pearson correlation coefficient indicated a significantly moderate correlation (r=0.57) between fatigue strength and loading frequency. The percentage of monoclinic phase was similar among the groups. Therefore, the use of loading frequencies up to 20Hz seems a good alternative to expedite the cycling strength fatigue tests in polycrystalline ceramics without significantly changing the fatigue behavior showed by zirconia in tests employing the frequency of the masticatory cycle. PMID- 26849032 TI - Two-Dimensional Visible Spectroscopy For Studying Colloidal Semiconductor Nanocrystals. AB - Possibilities offered by 2D visible spectroscopy for the investigation of the properties of excitons in colloidal semiconductor nanocrystals are overviewed, with a particular focus on their ultrafast dynamics. The technique of 2D electronic spectroscopy is illustrated with several examples showing its advantages compared to 1D ultrafast spectroscopic techniques (transient absorption and time-resolved photoluminescence). PMID- 26849033 TI - Projection of prediabetes and diabetes population size in Singapore using a dynamic Markov model. AB - BACKGROUND: The aim of the present study was to forecast the prevalence and number of adult Singapore residents with prediabetes and diabetes in 2035. METHODS: A dynamic Markov model with nine mutually exclusive states was developed based on the clinical course of diabetes using time-dependent rates and probabilities. A 1-year cycle over a 25-year time horizon from 2010 to 2035 was used in the model. With publicly available data and a chronic disease register, the model forecast annual disease burden by simulating transition of cohorts across different health states using prevalence rates, incidence rates, mortality rates, disease transition, disease detection, and complication rates. An aging index was used in the model in anticipation of population aging to minimize risks of underestimating disease burden. RESULTS: From 2010 to 2035, the number of Singapore residents with prediabetes and diabetes is projected to more than double, from 434 685 to 903 596 and from 373 104 to 823 802, respectively. The prevalence of prediabetes and diabetes will rise steadily from 15.5 % to 24.9 % and from 13.3 % to 22.7 %, respectively. By 2035, a further estimate of 733 174 and 100 250 patients with prediabetes and uncomplicated diabetes, respectively, will remain undiagnosed. The prevalence of detected and undetected complications is forecast to rise from 60.0 % in 2010 to 70.2 % by 2035. CONCLUSION: By 2035, the prevalence of prediabetes and diabetes among Singapore residents aged 21+ years is expected to be one in four and one in five, respectively. There is an impetus to adopt more aggressive interventions to contain disease progression. PMID- 26849034 TI - Evaluation of the influence of atipamezole on the postoperative analgesic effect of buprenorphine in cats undergoing a surgical ovariohysterectomy. AB - OBJECTIVE: To evaluate the influence of atipamezole on postoperative pain scores in cats. STUDY DESIGN: Controlled, randomized, masked clinical trial. ANIMALS: Twelve healthy female domestic cats. METHODS: Cats admitted for ovariohysterectomy (OVH) surgery were randomly allocated to group atipamezole (n = 6) or group saline (n = 6) and were premedicated with buprenorphine 20 MUg kg( 1) intramuscularly (IM) and alfaxalone 3.0 mg kg(-1) subcutaneously (SC). Anaesthesia was induced with alfaxalone intravenously (IV) to effect and maintained with isoflurane in oxygen. Ten minutes after extubation, cats from group atipamezole received IM atipamezole (0.0375 mg kg(-1) ) whereas group saline received an equivalent volume [0.0075 mL kg(-1) (0.003 mL kg(-1) IM)] of 0.9% saline. A validated multidimensional composite scale was used to assess pain prior to premedication and postoperatively (20 minutes after extubation). If postoperative pain scores dictated, rescue analgesia consisting of buprenorphine and meloxicam were administered. Pain score comparisons were made between the two groups using a Mann-Whitney exact test. Results are reported as the median and range. RESULTS: Preoperatively, all cats scored 0. At the postoperative pain evaluation, the pain scores from group atipamezole [16 (range, 12-20)] were not significantly different from group saline [18 (range, 15-23)] (p = 0.28). All cats required rescue analgesia post-operatively. CONCLUSIONS AND CLINICAL RELEVANCE: Atipamezole (0.0375 mg kg(-1) IM) administration did not significantly affect the postoperative pain scores in cats after OVH. Preoperative administration of buprenorphine (20 MUg kg(-1) IM) did not provide adequate postoperative analgesia for feline OVH. PMID- 26849035 TI - Nucleotide-dependent conformational changes of the AAA+ ATPase p97 revisited. AB - The ubiquitous AAA-ATPase p97 segregates ubiquitylated proteins from their molecular environment. Previous studies of the nucleotide-dependent conformational changes of p97 were inconclusive. Here, we determined its structure in the presence of ADP, AMP-PNP, or ATP-gammaS at 6.1-7.4 A resolution using single particle cryo-electron microscopy. Both AAA domains, D1 and D2, assemble into essentially six-fold symmetrical rings. The pore of the D1-ring remains essentially closed under all nucleotide conditions, whereas the D2-ring shows an iris-like opening for ADP. The largest conformational changes of p97 are 'swinging motions' of the N-terminal domains, which may enable segregation of ubiquitylated substrates from their environment. PMID- 26849036 TI - The role of competition in the phase shift to dominance of the zoanthid Palythoa cf. variabilis on coral reefs. AB - Phase shift phenomena are becoming increasingly common. However, they are also opportunities to better understand how communities are structured. In Southwest Atlantic coral reefs, a shift to the zoanthid Palythoa cf. variabilis dominance has been described. To test if competition drove this process, we carried out a manipulative experiment with three coral species. To estimate the natural frequency of encounters we assess the relationship between the proportion of encounters and this zoanthids coverage. The contact causes necrosis in 78% of coral colonies (6.47 +/- SD 7.92 cm(2)) in 118 days. We found a logarithmic relationship between the proportion of these encounters and the cover of P. cf. variabilis, where 5.5% coverage of this zoanthid is enough to put 50% of coral colonies in contact, increasing their partial mortality. We demonstrate that zoanthid coverage increase followed by coral mortality increase will reduce coral cover and that competition drives the phase shift process. PMID- 26849038 TI - Imaging of oligodendroglioma. AB - Oligodendroglioma are glial tumours, predominantly occurring in adults. Their hallmark molecular feature is codeletion of the 1p and 19q chromosome arms, which is not only of diagnostic but also of prognostic and predictive relevance. On imaging, these tumours characteristically show calcification, and they have a cortical-subcortical location, most commonly in the frontal lobe. Owing to their superficial location, there may be focal thinning or remodelling of the overlying skull. In contrast to other low-grade gliomas, minimal to moderate enhancement is commonly seen and perfusion may be moderately increased. This complicates differentiation from high-grade, anaplastic oligodendroglioma, in which enhancement and increased perfusion are also common. New enhancement in a previously non-enhancing, untreated tumour, however, is suggestive of malignant transformation, as is high growth rate. MR spectroscopy may further aid in the differentiation between low- and high-grade oligodendroglioma. A relatively common feature of recurrent disease is leptomeningeal dissemination, but extraneural spread is rare. Tumours with the 1p/19q codeletion more commonly show heterogeneous signal intensity, particularly on T2 weighted imaging; calcifications; an indistinct margin; and mildly increased perfusion and metabolism than 1p/19q intact tumours. For the initial diagnosis of oligodendroglioma, MRI and CT are complementary; MRI is superior to CT in assessing tumour extent and cortical involvement, whereas CT is most sensitive to calcification. Advanced and functional imaging techniques may aid in grading and assessing the molecular genotype as well as in differentiating between tumour recurrence and radiation necrosis, but so far no unequivocal method or combination of methods is available. PMID- 26849039 TI - Functional hypothalamic amenorrhoea: leptin treatment, dietary intervention and counselling as alternatives to traditional practice - systematic review. AB - Functional hypothalamic amenorrhoea (FHA) is a neuroendocrine disorder caused by an energy deficit and characterized by low leptin levels. Based on this, previous studies have suggested that leptin administration may play a crucial role in FHA treatment. However, FHA is also associated with abnormal psychosocial and dietary behaviour that needs to be addressed. In this context, this systematic review examined the efficacy of leptin treatment, non-pharmacological therapy and nutritional interventions in FHA. PubMed, Medline and Cochrane Library databases were searched in order to find relevant papers, including randomized controlled trials, clinical trials, prospective studies and case reports. The effects of different treatments on reproductive function, hormonal status and bone markers were recorded. Studies regarding other forms of treatment were excluded. In total, 111 papers were retrieved. After the removal of 29 duplicate papers, the abstracts and titles of 82 papers were examined. Subsequently, 53 papers were excluded based on title, and seven papers were omitted based on abstract. The remaining 11 papers were used: three based on leptin treatment, three regarding non-pharmacological treatment and five regarding dietary intervention. This literature review indicates that all of these treatment strategies improved reproductive function and hormonal status significantly, although conclusive results could not be drawn on bone markers. While leptin may be a promising new treatment, social aspects of FHA should also be addressed. As a result, a multifaceted therapeutic approach should be applied to treat affected women. PMID- 26849040 TI - Assessment of collagen versus non collagen coated anterior vaginal mesh in pelvic reconstructive surgery: prospective study. AB - OBJECTIVE: To evaluate the sonologic and clinical outcome of collagen coated (CC) versus non-collagen coated (NC) anterior vaginal mesh (AVM) for pelvic organ prolapse (POP) surgery. STUDY DESIGN: The study is a prospective observational study which included 122 patients who had symptomatic POP stage III and IV. AvaultaPlusTM (collagen coated, CC group) was compared to PerigeeTM (non collagen coated, NC group). Introital ultrasound morphology, measure of neovascularization by color Doppler and clinical outcomes were assessed. Student t test was used for comparison of pre- and post-operation continuous data (p value of <0.05). RESULTS: A total of 110 (CC group=50, NC group=60) women completed the study. A woman in the CC group developed ureteral injury. Both groups had comparable morphologic and clinical outcomes however, the onset of changes in mesh thickness and neovascularization occurred earlier in the NC group (1 month) compared to the CC group (6 months to 1 year). CONCLUSION: CC group was comparable to the NC group in terms of erosion rate, ultrasound and clinical assessment. Collagen coating may induce delayed inflammatory response however may also delay tissue integration. The onset of changes in mesh thickness and neovascularization may give us an insight toward utilization of collagen coated mesh for host-tissue integration. PMID- 26849037 TI - Targeting the tumour microenvironment in ovarian cancer. AB - The study of cancer initiation, growth, and metastasis has traditionally been focused on cancer cells, and the view that they proliferate due to uncontrolled growth signalling owing to genetic derangements. However, uncontrolled growth in tumours cannot be explained solely by aberrations in cancer cells themselves. To fully understand the biological behaviour of tumours, it is essential to understand the microenvironment in which cancer cells exist, and how they manipulate the surrounding stroma to promote the malignant phenotype. Ovarian cancer is the leading cause of death from gynaecologic cancer worldwide. The majority of patients will have objective responses to standard tumour debulking surgery and platinum-taxane doublet chemotherapy, but most will experience disease recurrence and chemotherapy resistance. As such, a great deal of effort has been put forth to develop therapies that target the tumour microenvironment in ovarian cancer. Herein, we review the key components of the tumour microenvironment as they pertain to this disease, outline targeting opportunities and supporting evidence thus far, and discuss resistance to therapy. PMID- 26849041 TI - Colonization of Beef Cattle by Shiga Toxin-Producing Escherichia coli during the First Year of Life: A Cohort Study. AB - Each year Shiga toxin-producing Escherichia coli (STEC) are responsible for 2.8 million acute illnesses around the world and > 250,000 cases in the US. Lowering the prevalence of this pathogen in animal reservoirs has the potential to reduce STEC outbreaks in humans by controlling its entrance into the food chain. However, factors that modulate the colonization and persistence of STEC in beef cattle remain largely unidentified. This study evaluated if animal physiological factors such as age, breed, sex, and weight gain influenced the shedding of STEC in beef cattle. A cohort of beef calves (n = 260) from a multi-breed beef calf population was sampled every three months after birth to measure prevalence and concentration of STEC during the first year of life. Metagenomic analysis was also used to understand the association between the STEC colonization and the composition of gut microflora. This study identified that beef calves were more likely to shed STEC during the first 6 months and that STEC shedding decreased as the animal matured. Animal breed group, sex of the calf, and average weight gain were not significantly associated with STEC colonization. The metagenomic analysis revealed for the first time that STEC colonization was correlated with a lower diversity of gut microflora, which increases as the cattle matured. Given these findings, intervention strategies that segregate younger animals, more likely to be colonized by STEC from older animals that are ready to be harvested, could be investigated as a method to reduce zoonotic transmission of STEC from cattle to humans. PMID- 26849043 TI - Implantation and Recovery of Long-Term Archival Transceivers in a Migratory Shark with High Site Fidelity. AB - We developed a long-term tagging method that can be used to understand species assemblages and social groupings associated with large marine fishes such as the Sand Tiger shark Carcharias taurus. We deployed internally implanted archival VEMCO Mobile Transceivers (VMTs; VEMCO Ltd. Nova Scotia, Canada) in 20 adult Sand Tigers, of which two tags were successfully recovered (10%). The recovered VMTs recorded 29,646 and 44,210 detections of telemetered animals respectively. To our knowledge, this is the first study to demonstrate a method for long-term (~ 1 year) archival acoustic transceiver tag implantation, retention, and recovery in a highly migratory marine fish. Results show low presumed mortality (n = 1, 5%), high VMT retention, and that non-lethal recovery after almost a year at liberty can be achieved for archival acoustic transceivers. This method can be applied to study the social interactions and behavioral ecology of large marine fishes. PMID- 26849042 TI - Burden of Influenza and Respiratory Syncytial Virus Infection in Pregnant Women and Infants Under 6 Months in Mongolia: A Prospective Cohort Study. AB - BACKGROUND: Pregnant women and infants under 6 months are at risk of influenza related complications. Limited information exists on their community burden of respiratory viruses. METHODS AND FINDINGS: This prospective, observational open cohort study was conducted in Baganuur district, Ulaanbaatar, Mongolia during 2013/14 and 2014/15 influenza seasons. Influenza-like illness (ILI) and severe acute respiratory infection (sARI) were identified by follow-up calls twice a week. For those identified, influenza and respiratory syncytical virus (RSV) were tested by point-of-care test kits. We calculated overall and stratified (by trimester or age group) incidence rates (IR) and used Cox proportional hazard regression for risk factor analyses. Among 1260 unvaccinated pregnant women enrolled, overall IRs for ILI, sARI and influenza A were 11.8 (95% confidence interval (C.I):11.2-12.4), 0.1 (95%C.I:0.0-0.4), and 1.7 (95%C.I:1.5-1.9) per 1,000person-days, respectively. One sARI case was influenza A positive. IRs and adjusted hazard ratios (Adj.HR) for ILI and influenza A were lowest in the third trimester. Those with co-morbidity were 1.4 times more likely to develop ILI [Adj.HR:1.4 (95%C.I:1.1-1.9)]. Among 1304 infants enrolled, overall ILI and sARI IRs were 15.2 (95%C.I:14.5-15.8) and 20.5 (95%C.I:19.7-21.3) per 1,000person days, respectively. From the tested ILI (77.6%) and sARI (30.6%) cases, the overall positivity rates were 6.3% (influenza A), 1.1% (influenza B) and 9.3% (RSV). Positivity rates of influenza A and RSV tend to increase with age. sARI cases were 1.4 times more likely to be male [Adj.HR:1.4 (95%C.I:1.1-1.8)]. Among all influenza A and RSV positive infants, 11.8% and 68.0% were respectively identified among sARI hospitalized cases. CONCLUSION: We observed low overall influenza A burden in both groups, though underestimation was likely due to point of-care tests used. For infants, RSV burden was more significant than influenza A. These findings would be useful for establishing control strategies for both viruses in Mongolia. PMID- 26849044 TI - Health Impact Index. Development and Validation of a Method for Classifying Comorbid Disease Measured against Self-Reported Health. AB - The objective of this study was to develop a method of classifying comorbid conditions that accounts for both the severity and joint effects of the diseases. The Tromso Study is a cohort study with a longitudinal design utilizing a survey approach with physical examinations in the Tromso municipality from 1974 to 2008, where in total 40051 subjects participated. We used Tromso 4 as reference population and the Norwegian Institute of Public Health (FHI) panel as validation population. Ordinal regression was used to assess the effect of comorbid disease on Self-Reported Health (SRH). The model is controlled for interaction between diseases, mental health, age, and gender. The health impact index estimated levels of SRH. The comparison of predicted and observed SRH showed no significant differences. Spearman's correlation showed that increasing levels of comorbidity were related to lower levels of SRH (RS = -0.36, p <.001). The Charlson Comorbidity Index(CCI) was also associated with SRH (r = -.25, p <.001). When focusing on only individuals with a comorbid disease, the relation between SRH and the Health Impact Index (HII) was strengthened (r = -.42, p <.001), while the association between SRH and CCI was attenuated (r = -.14, p <.001). CCI was designed to control for comorbid conditions when survival/mortality is the outcome of interest but is inaccurate when the outcome is SRH. We conclude that HII should be used when SRH is not available, and well-being or quality of survival/life is the outcome of interest. PMID- 26849045 TI - Dramatic Number Variation of R Genes in Solanaceae Species Accounted for by a Few R Gene Subfamilies. AB - Most disease resistance genes encode nucleotide-binding-site (NBS) and leucine rich-repeat (LRR) domains, and the NBS-LRR encoding genes are often referred to as R genes. Using newly developed approach, 478, 485, 1,194, 1,665, 2,042 and 374 R genes were identified from the genomes of tomato Heinz1706, wild tomato LA716, potato DM1-3, pepper Zunla-1 and wild pepper Chiltepin and tobacco TN90, respectively. The majority of R genes from Solanaceae were grouped into 87 subfamilies, including 16 TIR-NBS-LRR (TNL) and 71 non-TNL subfamilies. Each subfamily was annotated manually, including identification of intron/exon structure and intron phase. Interestingly, TNL subfamilies have similar intron phase patterns, while the non-TNL subfamilies have diverse intron phase due to frequent gain of introns. Prevalent presence/absence polymorphic R gene loci were found among Solanaceae species, and an integrated map with 427 R loci was constructed. The pepper genome (2,042 in Chiltepin) has at least four times of R genes as in tomato (478 in Heinz1706). The high number of R genes in pepper genome is due to the amplification of R genes in a few subfamilies, such as the Rpi-blb2 and BS2 subfamilies. The mechanism underlying the variation of R gene number among different plant genomes is discussed. PMID- 26849046 TI - Association of Adiposity and Mental Health Functioning across the Lifespan: Findings from Understanding Society (The UK Household Longitudinal Study). AB - BACKGROUND: Evidence on the adiposity-mental health associations is mixed, with studies finding positive, negative or no associations, and less is known about how these associations may vary by age. OBJECTIVE: To examine the association of adiposity -body mass index (BMI), waist circumference (WC) and percentage body fat (BF%)- with mental health functioning across the adult lifespan. METHODS: Data from 11,257 participants (aged 18+) of Understanding Society: the UK Household Longitudinal Study (waves 2 and 3, 5/2010-7/2013) were employed. Regressions of mental health functioning, assessed by the Mental Component Summary (MCS-12) and the General Health Questionnaire (GHQ-12), on adiposity measures (continuous or dichotomous indicators) were estimated adjusted for covariates. Polynomial age-adiposity interactions were estimated. RESULTS: Higher adiposity was associated with poorer mental health functioning. This emerged in the 30s, increased up to mid-40s (all central adiposity and obesity-BF% measures) or early 50s (all BMI measures) and then decreased with age. Underlying physical health generally accounted for these associations except for central adiposity, where associations remained statistically significant from the mid-30s to 50s. Cardiovascular, followed by arthritis and endocrine, conditions played the greatest role in attenuating the associations under investigation. CONCLUSIONS: We found strong age-specific patterns in the adiposity-mental health functioning association that varied across adiposity measures. Underlying physical health had the dominant role in attenuating these associations. Policy makers and health professionals should target increased adiposity, mainly central adiposity, as it is a risk factor for poor mental health functioning in those aged between mid-30s to 50 years. PMID- 26849047 TI - Antibiotics in Drinking Water in Shanghai and Their Contribution to Antibiotic Exposure of School Children. AB - A variety of antibiotics have been found in aquatic environments, but antibiotics in drinking water and their contribution to antibiotic exposure in human are not well-explored. For this, representative drinking water samples and 530 urine samples from schoolchildren were selected in Shanghai, and 21 common antibiotics (five macrolides, two beta-lactams, three tetracyclines, four fluoquinolones, four sulfonamides, and three phenicols) were measured in water samples and urines by isotope dilution two-dimensional ultraperformance liquid chromatography coupled with high-resolution quadrupole time-of-flight mass spectrometry. Drinking water included 46 terminal tap water samples from different spots in the distribution system of the city, 45 bottled water samples from 14 common brands, and eight barreled water samples of different brands. Of 21 antibiotics, only florfenicol and thiamphenicol were found in tap water, with the median concentrations of 0.0089 ng/mL and 0.0064 ng/mL, respectively; only florfenicol was found in three bottled water samples from a same brand, with the concentrations ranging from 0.00060 to 0.0010 ng/mL; no antibiotics were found in barreled water. In contrast, besides florfenicol and thiamphenicol, an additional 17 antibiotics were detected in urine samples, and the total daily exposure doses and detection frequencies of florfenicol and thiamphenicol based on urine samples were significantly and substantially higher than their predicted daily exposure doses and detection frequencies from drinking water by Monte Carlo Simulation. These data indicated that drinking water was contaminated by some antibiotics in Shanghai, but played a limited role in antibiotic exposure of children. PMID- 26849048 TI - Albendazole and Corticosteroids for the Treatment of Solitary Cysticercus Granuloma: A Network Meta-analysis. AB - BACKGROUND: Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG. METHODS AND PRINCIPAL FINDINGS: PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (Pbest) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10-0.93, Pbest 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24-7.95, Pbest 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies. CONCLUSIONS: Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available. PMID- 26849049 TI - Acidic pH-Induced Conformations and LAMP1 Binding of the Lassa Virus Glycoprotein Spike. AB - Lassa virus is an enveloped, bi-segmented RNA virus and the most prevalent and fatal of all Old World arenaviruses. Virus entry into the host cell is mediated by a tripartite surface spike complex, which is composed of two viral glycoprotein subunits, GP1 and GP2, and the stable signal peptide. Of these, GP1 binds to cellular receptors and GP2 catalyzes fusion between the viral envelope and the host cell membrane during endocytosis. The molecular structure of the spike and conformational rearrangements induced by low pH, prior to fusion, remain poorly understood. Here, we analyzed the three-dimensional ultrastructure of Lassa virus using electron cryotomography. Sub-tomogram averaging yielded a structure of the glycoprotein spike at 14-A resolution. The spikes are trimeric, cover the virion envelope, and connect to the underlying matrix. Structural changes to the spike, following acidification, support a viral entry mechanism dependent on binding to the lysosome-resident receptor LAMP1 and further dissociation of the membrane-distal GP1 subunits. PMID- 26849052 TI - Correction: A Computational Study of the Factors Influencing the PVC-Triggering Ability of a Cluster of Early Afterdepolarization-Capable Myocytes. PMID- 26849050 TI - Clonal Strain Persistence of Candida albicans Isolates from Chronic Mucocutaneous Candidiasis Patients. AB - Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency disorder characterised by susceptibility to chronic Candida and fungal dermatophyte infections of the skin, nails and mucous membranes. Molecular epidemiology studies of CMC infection are limited in number and scope and it is not clear whether single or multiple strains inducing CMC persist stably or are exchanged and replaced. We subjected 42 C. albicans individual single colony isolates from 6 unrelated CMC patients to multilocus sequence typing (MLST). Multiple colonies were typed from swabs taken from multiple body sites across multiple time points over a 17-month period. Among isolates from each individual patient, our data show clonal and persistent diploid sequence types (DSTs) that were stable over time, identical between multiple infection sites and exhibit azole resistant phenotypes. No shared origin or common source of infection was identified among isolates from these patients. Additionally, we performed C. albicans MLST SNP genotype frequency analysis to identify signatures of past loss of heterozygosity (LOH) events among persistent and azole resistant isolates retrieved from patients with autoimmune disorders including CMC. PMID- 26849053 TI - Adjunctive Brexpiprazole: A Review in Major Depressive Disorder. AB - Brexpiprazole (Rexulti((r))) is a serotonin-dopamine activity modulator, with a unique receptor binding profile and low intrinsic D2 activity suggestive of a lower potential than aripiprazole to cause activation-like adverse effects, such as akathisia. The drug was recently approved by the US FDA for adjunctive therapy with antidepressant treatment (ADT) in patients with major depressive disorder (MDD). In two phase III trials, adjunctive oral brexpiprazole 2 or 3 mg once daily was more effective than monotherapy with ADT in improving depressive symptoms in adults with MDD who demonstrated an incomplete response to previous treatment with ADT. Adjunctive brexpiprazole was generally well tolerated in clinical trials, which included treatment periods of up to 52 weeks. Results of ongoing trials should help position the drug in the treatment of MDD. In the meantime, brexpiprazole provides a valid option for patients with persistent symptoms despite standard antidepressant therapy. PMID- 26849051 TI - Lactobacillus casei Exerts Anti-Proliferative Effects Accompanied by Apoptotic Cell Death and Up-Regulation of TRAIL in Colon Carcinoma Cells. AB - Probiotic microorganisms such as lactic acid bacteria (LAB) exert a number of strain-specific health-promoting activities attributed to their immunomodulatory, anti-inflammatory and anti-carcinogenic properties. Despite recent attention, our understanding of the biological processes involved in the beneficial effects of LAB strains is still limited. To this end, the present study investigated the growth-inhibitory effects of Lactobacillus casei ATCC 393 against experimental colon cancer. Administration of live Lactobacillus casei (as well as bacterial components thereof) on murine (CT26) and human (HT29) colon carcinoma cell lines raised a significant concentration- and time-dependent anti-proliferative effect, determined by cell viability assays. Specifically, a dramatic decrease in viability of colon cancer cells co-incubated with 10(9) CFU/mL L. casei for 24 hours was detected (78% for HT29 and 52% for CT26 cells). In addition, live L. casei induced apoptotic cell death in both cell lines as revealed by annexin V and propidium iodide staining. The significance of the in vitro anti proliferative effects was further confirmed in an experimental tumor model. Oral daily administration of 10(9) CFU live L. casei for 13 days significantly inhibited in vivo growth of colon carcinoma cells, resulting in approximately 80% reduction in tumor volume of treated mice. Tumor growth inhibition was accompanied by L. casei-driven up-regulation of the TNF-related apoptosis inducing ligand TRAIL and down-regulation of Survivin. Taken together, these findings provide evidence for beneficial tumor-inhibitory, anti-proliferative and pro-apoptotic effects driven by this probiotic LAB strain. PMID- 26849054 TI - Potential Role of Oestrogen Modulation in the Treatment of Neurocognitive Deficits in Schizophrenia. AB - Cognitive deficits are prevalent in schizophrenia, and these deficits represent a disabling aspect of the illness for which there are no current effective treatments. Recent work has shown that sex hormone levels correlate with brain activity and cognitive abilities differentially in patients with schizophrenia relative to healthy control groups. There is emerging evidence suggesting that oestrogen-based therapies may be useful in reversing the cognitive deficits associated with schizophrenia. To date, the results from clinical trials using oestrogen-based therapies to reverse cognitive impairment in schizophrenia have shown that the selective oestrogen receptor modulator raloxifene may be useful to improve attention, memory, learning and the associated brain activity in chronically ill men and women with schizophrenia or schizoaffective disorder. While these findings of cognitive enhancement with a selective oestrogen receptor modulator in people with schizophrenia are encouraging, additional studies will be required to replicate the initial results, assess the time frame of treatment effects, identify biomarkers in subsets of patients who may be more likely to optimally respond to treatment, and identify a more precise mechanism of action, which may include anti-inflammatory effects of oestrogen-based treatments. PMID- 26849056 TI - Complement System in the Pathogenesis of Benign Lymphoepithelial Lesions of the Lacrimal Gland. AB - OBJECTIVE: We aimed to examine the potential involvement of local complement system gene expression in the pathogenesis of benign lymphoepithelial lesions (BLEL) of the lacrimal gland. METHODS: We collected data from 9 consecutive pathologically confirmed patients with BLEL of the lacrimal gland and 9 cases with orbital cavernous hemangioma as a control group, and adopted whole genome microarray to screen complement system-related differential genes, followed by RT PCR verification and in-depth enrichment analysis (Gene Ontology analysis) of the gene sets. RESULTS: The expression of 14 complement system-related genes in the pathologic tissue, including C2, C3, ITGB2, CR2, C1QB, CR1, ITGAX, CFP, C1QA, C4B|C4A, FANCA, C1QC, C3AR1 and CFHR4, were significantly upregulated while 7 other complement system-related genes, C5, CFI, CFHR1|CFH, CFH, CD55, CR1L and CFD were significantly downregulated in the lacrimal glands of BLEL patients. The microarray results were consistent with RT-PCR analysis results. Immunohistochemistry analysis of C3c and C1q complement component proteins in the resected tissue were positive in BLEL patients, while the control group had negative expression of these proteins. Gene ontology (GO) analysis revealed that activation of the genes of complement system-mediated signaling pathways were the most enriched differential gene group in BLEL patients. CONCLUSIONS: Local expression of complement components is prominently abnormal in BLEL, and may well play a role in its pathogenesis. PMID- 26849055 TI - Fracture Healing Is Delayed in Immunodeficient NOD/scid- IL2Rgamma cnull Mice. AB - Following bone fracture, the repair process starts with an inflammatory reaction at the fracture site. Fracture healing is disturbed when the initial inflammation is increased or prolonged, whereby, a balanced inflammatory response is anticipated to be crucial for fracture healing, because it may induce down-stream responses leading to tissue repair. However, the impact of the immune response on fracture healing remains poorly understood. Here, we investigated bone healing in NOD/scid-IL2Rgammacnull mice, which exhibit severe defects in innate and adaptive immunity, by biomechanical testing, histomorphometry and micro-computed tomography. We demonstrated that NOD/scid-IL2Rgammacnull mice exhibited normal skeletal anatomy and a mild bone phenotype with a slightly reduced bone mass in the trabecular compartment in comparison to immunocompetent Balb/c mice. Fracture healing was impaired in immunodeficient NOD/scid-IL2Rgammacnull mice. Callus bone content was unaffected during the early healing stage, whereas it was significantly reduced during the later healing period. Concomitantly, the amount of cartilage was significantly increased, indicating delayed endochondral ossification, most likely due to the decreased osteoclast activity observed in cells isolated from NOD/scid-IL2Rgammacnull mice. Our results suggest that--under aseptic, uncomplicated conditions--the immediate immune response after fracture is non-essential for the initiation of bone formation. However, an intact immune system in general is important for successful bone healing, because endochondral ossification is delayed in immunodeficient NOD/scid-IL2Rgammacnull mice. PMID- 26849057 TI - Potent Inhibition of Pseudogymnoascus destructans, the Causative Agent of White Nose Syndrome in Bats, by Cold-Pressed, Terpeneless, Valencia Orange Oil. AB - The causative agent of White-nose Syndrome (WNS), Pseudogymnoascus destructans, has been shown to be fatal to several species of bats in North America. To date, no compounds or chemical control measures have been developed which eliminates the growth of the fungus in the environment or in affected animals. In the current study, we evaluated the activity of cold-pressed, terpeneless orange oil (CPT) against multiple isolates of P. destructans in vitro. For all assays, a modified Kirby-Bauer disk diffusion assay was used. Standardized spore suspensions were prepared, adjusted to a specific optical density, and used to plate fungal lawns. Plates were incubated at either 15 degrees C or 4 degrees C for up to 6 months and checked at regular intervals for growth. Once controls had grown, zones of inhibition were measured (mm) on test plates and compared to those obtained using current antifungal drugs. All P. destructans isolates were completely inhibited by 100% CPT (10 MUL) at 1 month of incubation regardless of temperature (4 degrees C and 15 degrees C). Complete inhibition persisted up to 6 months following a single exposure at this concentration. Of the standard antifungals, only amphotericin B demonstrated any activity, resulting in zone diameters ranging from 58 mm to 74 mm. CPT, at the highest concentration tested (100%), had no significant effect against a variety of other environmental organisms including various filamentous fungi, bacteria and aerobic actinomycetes. Given that CPT is relatively non-toxic, the possibility exists that the all-natural, mixture could be used as an environmental pre-treatment to eradicate P. destructans from bat habitats. Additional studies are needed to assess any undesirable effects of CPT on bat behavior and health and overall impacts on other members of the interconnected ecosystem(s). PMID- 26849058 TI - Experimental Evaluation of a Braille-Reading-Inspired Finger Motion Adaptive Algorithm. AB - Braille reading is a complex process involving intricate finger-motion patterns and finger-rubbing actions across Braille letters for the stimulation of appropriate nerves. Although Braille reading is performed by smoothly moving the finger from left-to-right, research shows that even fluent reading requires right to-left movements of the finger, known as "reversal". Reversals are crucial as they not only enhance stimulation of nerves for correctly reading the letters, but they also show one to re-read the letters that were missed in the first pass. Moreover, it is known that reversals can be performed as often as in every sentence and can start at any location in a sentence. Here, we report experimental results on the feasibility of an algorithm that can render a machine to automatically adapt to reversal gestures of one's finger. Through Braille reading-analogous tasks, the algorithm is tested with thirty sighted subjects that volunteered in the study. We find that the finger motion adaptive algorithm (FMAA) is useful in achieving cooperation between human finger and the machine. In the presence of FMAA, subjects' performance metrics associated with the tasks have significantly improved as supported by statistical analysis. In light of these encouraging results, preliminary experiments are carried out with five blind subjects with the aim to put the algorithm to test. Results obtained from carefully designed experiments showed that subjects' Braille reading accuracy in the presence of FMAA was more favorable then when FMAA was turned off. Utilization of FMAA in future generation Braille reading devices thus holds strong promise. PMID- 26849059 TI - Pharmacodynamics and pharmacokinetics of elbasvir and grazoprevir in the treatment of hepatitis C. AB - INTRODUCTION: Approximately 130 - 150 million people have chronic hepatitis C virus (HCV) infection and upwards of 500,000 deaths annually are attributed to HCV related liver disease worldwide. Pegylated interferon and ribavirin have been the mainstay of treatment for greater than 25 years until recent advent of protease inhibitors which has led to all oral HCV treatment regimens that have changed the outlook of hepatitis C treatment. AREAS COVERED: This review provides summary of pharmacokinetics, pharmacodynamics, efficacy and safety of grazoprevir/elbasvir therapy for treatment of HCV infection. EXPERT OPINION: Grazoprevir/elbasvir provides an all-oral once daily treatment option for HCV infection with high rates of efficacy and tolerability in a pangenotypic fashion. It highly efficacious in treating patients with cirrhosis, patients who have previously failed treatment with pegylated interferon and ribavirin, and patients with HIV co-infection. Grazoprevir/elbasvir has demonstrated higher barrier to resistance even in the presence of variants associated with resistance such as Q41R, F43S, R155K, V36M, T54S, and D168. It is one of only few HCV treatment regimens evaluated for use in patients with advanced chronic kidney disease and dialysis. It is a very promising regimen for treatment of HCV infection. PMID- 26849061 TI - Predicting Flow Reversals in a Computational Fluid Dynamics Simulated Thermosyphon Using Data Assimilation. AB - A thermal convection loop is a annular chamber filled with water, heated on the bottom half and cooled on the top half. With sufficiently large forcing of heat, the direction of fluid flow in the loop oscillates chaotically, dynamics analogous to the Earth's weather. As is the case for state-of-the-art weather models, we only observe the statistics over a small region of state space, making prediction difficult. To overcome this challenge, data assimilation (DA) methods, and specifically ensemble methods, use the computational model itself to estimate the uncertainty of the model to optimally combine these observations into an initial condition for predicting the future state. Here, we build and verify four distinct DA methods, and then, we perform a twin model experiment with the computational fluid dynamics simulation of the loop using the Ensemble Transform Kalman Filter (ETKF) to assimilate observations and predict flow reversals. We show that using adaptively shaped localized covariance outperforms static localized covariance with the ETKF, and allows for the use of less observations in predicting flow reversals. We also show that a Dynamic Mode Decomposition (DMD) of the temperature and velocity fields recovers the low dimensional system underlying reversals, finding specific modes which together are predictive of reversal direction. PMID- 26849060 TI - Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients. AB - OBJECTIVE: We reviewed the current literature regarding antiretroviral (ARV) sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. METHODS: A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. RESULTS: Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. CONCLUSIONS: The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the effectiveness and tolerability of dual therapy regimens, it remains unclear whether these potential benefits can be maintained long-term. Appropriately powered studies with longer follow-up periods are needed to more definitively assess potential toxicity reduction advantages with dual therapy. PMID- 26849063 TI - Surgical repair of rhegmatogenous retinal detachment in eyes harboring active retinoblastoma. AB - BACKGROUND: Intraocular surgeries are classically contraindicated for patients with active Retinoblastoma (RB) due to the risk of tumor dissemination. Unfortunately, RB treatment may be complicated by rhegmatogenous retinal detachment (RD) that necessitates surgical repair especially in a child who is monocular from enucleation of the contralateral eye. OBJECTIVE: To assess the outcome of surgical repair of rhegmatogenous RD in children with RB using non drainage scleral buckling. RESULTS: Rhegmatogenous RD was diagnosed in three eyes of three children during treatment of RB; one of which had associated tractional RD. All patients received systemic chemotherapy, cryotherapy, and thermal therapy. RD was present at the site of the most recent cryotherapy in all of the three eyes. RD was repaired externally with a scleral buckling procedure without subretinal fluid drainage in each of the three eyes. The retina reattached completely after surgery in two eyes and only partially in one eye. In one eye, which had the tractional component, complete retinal attachment was not achieved and thus enucleation was performed. Orbital or metastatic retinoblastoma was detected in none of the cases on follow-up at 6-36 months. CONCLUSIONS: Scleral buckling without subretinal fluid drainage is a useful technique for repairing rhegmatogenous RD in eyes with RB mainly in the absence of a tractional component. PMID- 26849062 TI - Constitutively Active MAVS Inhibits HIV-1 Replication via Type I Interferon Secretion and Induction of HIV-1 Restriction Factors. AB - Type I interferon is known to inhibit HIV-1 replication through the induction of interferon stimulated genes (ISG), including a number of HIV-1 restriction factors. To better understand interferon-mediated HIV-1 restriction, we constructed a constitutively active form of the RIG-I adapter protein MAVS. Constitutive MAVS was generated by fusion of full length MAVS to a truncated form of the Epstein Barr virus protein LMP1 (DeltaLMP1). Supernatant from DeltaLMP1 MAVS-transfected 293T cells contained high levels of type I interferons and inhibited HIV replication in both TZM-bl and primary human CD4+ T cells. Supernatant from DeltaLMP1-MAVS-transfected 293T cells also inhibited replication of VSV-G pseudotyped single cycle SIV in TZM-bl cells, suggesting restriction was post-entry and common to both HIV and SIV. Gene array analysis of DeltaLMP1-MAVS transfected 293T cells and trans-activated CD4+ T cells showed significant upregulation of ISG, including previously characterized HIV restriction factors Viperin, Tetherin, MxB, and ISG56. Interferon blockade studies implicated interferon-beta in this response. In addition to direct viral inhibition, DeltaLMP1-MAVS markedly enhanced secretion of IFN-beta and IL-12p70 by dendritic cells and the activation and maturation of dendritic cells. Based on this immunostimulatory activity, an adenoviral vector (Ad5) expressing DeltaLMP1-MAVS was tested as a molecular adjuvant in an HIV vaccine mouse model. Ad5-Gag antigen combined with Ad5-DeltaLMP1-MAVS enhanced control of vaccinia-gag replication in a mouse challenge model, with 4/5 animals showing undetectable virus following challenge. Overall, DeltaLMP1-MAVS is a promising reagent to inhibit HIV-1 replication in infected tissues and enhance vaccine-mediated immune responses, while avoiding toxicity associated with systemic type I interferon administration. PMID- 26849064 TI - Treatment adherence in newly diagnosed type 2 diabetes: patient characteristics and long-term impact of adherence on inpatient care utilization. AB - OBJECTIVES: The purpose of this study was to evaluate the impact of antidiabetic medication adherence on hospital utilization in patients with newly diagnosed type 2 diabetes mellitus (T2D). This study specifically analyzed patients with newly diagnosed T2D with the intent of lessening intragroup disease severity differences, and adjusting for a range of other clinical and demographic characteristics. METHODS: This retrospective US claims database study evaluated adults with newly diagnosed T2D who started antidiabetic medications in 2005 2009, had >= 2 antidiabetic medication claims after their first (baseline). Medication adherence was evaluated using the medication possession ratio (MPR) of any or all antidiabetic medication(s) during the 3-year post-baseline period. Repeated-measures analyses examined changes in inpatient utilization from the pre to post-baseline period. The impact of adherence on hospital utilization during the post-baseline period was evaluated with a logistic regression model to adjust for confounding factors. RESULTS: The study included 192,717 patients (mean age, 55.0 years). Mean MPR for antidiabetic therapy was 0.74. MPR was highest in elderly patients and Medicare beneficiaries. Mean annualized inpatient admissions during the 3-year post-baseline period were significantly lower in patients with MPR >= 0.80 (1.4) than in those with MPR < 0.80 (2.2; P < 0.05). Logistic regression analysis, adjusting for patient characteristics and prior inpatient utilization, showed 39% lower odds of hospitalization (OR = 0.61; 95% CI = 0.534 0.693) for patients with MPR >= 0.80. People with T2D-related complications or hospitalization had approximately 2- to 3-fold higher risk of subsequent hospitalization. CONCLUSIONS: In newly diagnosed T2D patients with antidiabetic therapy in the first three ensuing years, higher antidiabetic medication adherence was significantly associated with lower hospital inpatient utilization before and after adjusting for patient characteristics. PMID- 26849066 TI - Concurrent Increases and Decreases in Local Stability and Conformational Heterogeneity in Cu, Zn Superoxide Dismutase Variants Revealed by Temperature Dependence of Amide Chemical Shifts. AB - The chemical shifts of backbone amide protons in proteins are sensitive reporters of local structural stability and conformational heterogeneity, which can be determined from their readily measured linear and nonlinear temperature dependences, respectively. Here we report analyses of amide proton temperature dependences for native dimeric Cu, Zn superoxide dismutase (holo pWT SOD1) and structurally diverse mutant SOD1s associated with amyotrophic lateral sclerosis (ALS). Holo pWT SOD1 loses structure with temperature first at its periphery and, while having extremely high global stability, nevertheless exhibits extensive conformational heterogeneity, with ~1 in 5 residues showing evidence for population of low energy alternative states. The holo G93A and E100G ALS mutants have moderately decreased global stability, whereas V148I is slightly stabilized. Comparison of the holo mutants as well as the marginally stable immature monomeric unmetalated and disulfide-reduced (apo(2SH)) pWT with holo pWT shows that changes in the local structural stability of individual amides vary greatly, with average changes corresponding to differences in global protein stability measured by differential scanning calorimetry. Mutants also exhibit altered conformational heterogeneity compared to pWT. Strikingly, substantial increases as well as decreases in local stability and conformational heterogeneity occur, in particular upon maturation and for G93A. Thus, the temperature-dependence of amide shifts for SOD1 variants is a rich source of information on the location and extent of perturbation of structure upon covalent changes and ligand binding. The implications for potential mechanisms of toxic misfolding of SOD1 in disease and for general aspects of protein energetics, including entropy-enthalpy compensation, are discussed. PMID- 26849067 TI - The Inhibitory Effect of Rapamycin on Toll Like Receptor 4 and Interleukin 17 in the Early Stage of Rat Diabetic Nephropathy. AB - BACKGROUND/AIMS: There is increasing evidence showing that innate immune responses and inflammatory processes play an important role in the development and progression of diabetic nephropathy (DN). The potential effect of innate immunity in the early stage of DN is still unclear. Toll-Like-Receptor 4 (TLR4) is vigorously involved in the progress of kidney diseases in a sterile environment. The activation of the interleukin 17 (IL-17) pathway produces inflammatory cytokines, appearing in various kidney diseases. Unfortunately the relationship between TLR4 and IL-17 has not been investigated in diabetic nephropathy to date. The aim of this study is to investigate whether mammalian target of rapamycin (mTOR) inhibition may be dependent on TLR4 signaling and the pro-inflammatory factor IL-17 to delay the progression of DN. METHODS: Streptozotocin (STZ)-induced diabetic rats were randomly assigned to 3 experimental groups: a diabetic nephropathy group (DN, n = 6); and a diabetic nephropathy treated with rapamycin group (Rapa, n = 6) and a control group (Control, n =6). Body weight, fasting blood sugar, and 24h urine albumin were assessed at week 2, week 4 and week 8. Renal tissues were harvested for H&E, PAS staining, as well as an immunohistochemistry assay for TLR4 and IL-17. TLR4 quantitative expression was measured by Western-Blot analysis and RT-PCR. RESULTS: Our results demonstrated that the expression of both TLR4 and IL-17 were upregulated in early stage DN and reduced by rapamycin. TLR4 and IL-17 both increased and positively related to 24h urinary albumin and kidney/weight ratio. However, neither TLR4 nor IL-17 made a significant difference on fasting blood sugar. CONCLUSIONS: Taken together, our results confirm and extend previous studies identifying the significance of the TLR4 and Th17 pathways in development of early stage DN. Furthermore, we suggest this overexpression of TLR4 might be involved in the immunopathogenesis of DN through activation of Th17 cells. Rapamycin may attenuate DN via reduction of the TLR4 signaling pathway and Th17 cells signaling. Although the underlying mechanisms need to be explored, the observed increase of TLR4 and IL-17 during the early stages of DN and their suppression with rapamycin treatment suggest the importance of TLR4 and IL-17 in DN pathophysiology. PMID- 26849068 TI - Reinvestigation of the Branimycin Stereochemistry at Position 17-C. AB - A conformational study of branimycin was performed using single-crystal X-ray crystallography to characterize the solid-state form, while a combination of NMR spectroscopy and molecular modeling was employed to gain information about the solution structure. Comparison of the crystal structure with its solution counterpart showed no significant differences in conformation, confirming the relative rigidity of the tricyclic system. However, these experiments revealed that the formerly proposed stereochemistry of branimycin at 17-C should be revised. PMID- 26849069 TI - Prior expectations about where other people are likely to direct their attention systematically influence gaze perception. AB - Different locations in the visual environment vary greatly in terms of how likely they are to draw a person's attention. When inferring the most likely target of another person's gaze, it would therefore be a reasonable strategy to incorporate expectations about the relative visual salience of these various locations, weighing this prior knowledge against incoming social signals (e.g., eye cues). This Bayesian approach to modeling gaze perception has informed computer vision techniques, but whether this model accounts well for human performance remains an untested hypothesis. We present subjects with a "gazer" fixating his eyes on various locations on a two-dimensional surface, and project arbitrary photographic images onto that surface. Subjects judge where the gazer is looking in each image. A full Bayesian model, which takes image salience information into account, fits subjects' gaze judgments better than a reduced model that only considers the perceived direction of the gazer's eyes. Varying the amount of time the subject is allowed to view the gazer reveals that center bias tends to dominate gaze judgments early, whereas salient features specific to the projected image influence judgments at longer viewing durations. PMID- 26849070 TI - Rapid and accurate processing of multiple objects in briefly presented scenes. AB - Humans can detect multiple objects in briefly presented natural visual scenes, but the mechanisms through which the objects are segmented from the background and consciously accessed remain open. By asking participants to report how many humans natural photos presented for 50 ms contain, we show that up to three items can be rapidly enumerated from natural scenes without compromising speed or accuracy. In contrast to standard parallel and serial models of object selection, our results revealed that the participants were fastest in enumerating two objects; even enumerating one single item required additional processing time. Also enumeration accuracy slightly increased in the subitizing range as number increased. Our results suggest that the visual system is tuned to process multiple items, which may underlie spatial and numerical cognition, and be beneficial in real-world situations that often require dealing with more than one object at a time. PMID- 26849072 TI - Analysis of IL-10 and IL-6 Gene Polymorphisms and Their Serum Levels in Patients with Brucellosis: A Case Control Study. AB - BACKGROUND: It seems that polymorphism in the regulatory areas of cytokine genes affects the cytokine production capacity and may play a role in the development of infectious diseases. Interleukin-10 (IL-10) and Interleukin-6 (IL-6), which are cytokines of Th2, cause the macrophage become inactive and patient conditions get worse. METHODS: In this case-control study, 60 patients with brucellosis and 60 healthy participants were recruited. IL-10 genotyping at positions -1082 (G/A), -819 (C/T), and -592 (C/A) and IL-6 genotyping at position -174 (G/C) were analyzed by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) methods. The levels of IL-10 and IL-6 were determined by a sandwich enzyme-linked immunosorbent assay in sera of study population. RESULTS: The AA and CC genotypes of the IL-10 gene at positions -1082 G/A and -819 C/T were significantly more frequent in patients in comparison to controls, respectively. The AG genotype of the IL-10 gene at positions -1082 G/A was significantly more frequent in control groups than the patients. Serum levels of IL-10 and IL-6 were significantly more frequent in the patients than in the control groups. CONCLUSIONS: Our study showed that the AA and CC genotypes at positions -1082 and -819 are very important, respectively. These results suggest that IL-10 (-1082 G/A) GG genotype may be considered as a risk factor for brucellosis, while the AG genotype might be a protective factor against the disease. PMID- 26849073 TI - Physiological uptake values of 18F-FDG in long bones of the lower extremity on PET/CT imaging. AB - INTRODUCTION: Fluorine-18 fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) has proven to be a valuable imaging modality with high diagnostic accuracy for the detection of bone infections. However, the physiological uptake values for F FDG in the long bones of the lower extremity have not been established yet. This hampers correct interpretation of a F-FDG-PET/CT scan. PURPOSE: The purpose of this study was to determine the physiological uptake values of F-FDG in the long bones of the lower extremities, including the femur and the tibia. PATIENTS AND METHODS: We retrospectively analyzed the F-FDG-PET/CT scan of 84 consecutive patients from our database. F-FDG uptake parameters included mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax). Both SUVs were determined in the diaphyseal region of the femur and the tibia. RESULTS: SUVmean for the femoral diaphysis was 0.46 [95% confidence interval (CI) 0.42 0.49] and SUVmax was 0.81 (95% CI 0.74-0.88). For the tibial diaphysis, SUVmean was 0.34 (95% CI 0.32-0.37) and SUVmax was 0.61 (95% CI 0.56-0.65). SUVmean and SUVmax of the femur were significantly higher than that of the tibia (both P<0.01). SUVs for men were not significantly different from that for women and did not discriminate between age classes. CONCLUSION: For a correct interpretation of the F-FDG-PET/CT scan, we have determined the F-FDG uptake values in the long bones of the femur and the tibia. A SUVmean less than 0.5 and a SUVmax less than 0.8 can be considered as normal bone, irrespective of sex or age. PMID- 26849074 TI - The Immunomodulatory Potential of Mesenchymal Stromal Cells: A Story of a Regulatory Network. AB - Mesenchymal stromal cells (MSCs) have recently been the subject of great interest in the fields of regenerative medicine and immunotherapy due to their unique biological properties. In particular, MSCs possess immunoregulatory properties that can modulate immune as well as inflammatory responses. Although there are many studies about MSC immunomodulation, several complex and conflicting mechanisms have been reported. Herein, we aim to review these mechanisms and identify a link between these pathways. We focus on human studies in which bone marrow-derived MSCs and T cells were investigated. We propose that MSC-induced immunomodulation exists as a network where converging regulatory pathways compete to establish a tolerogenic state. As interleukin-10 seems to play a central role in this network, we also discuss the relationship between this cytokine and other regulatory factors in the context of immunomodulation. PMID- 26849071 TI - Future Directions in Childhood Adversity and Youth Psychopathology. AB - Despite long-standing interest in the influence of adverse early experiences on mental health, systematic scientific inquiry into childhood adversity and developmental outcomes has emerged only recently. Existing research has amply demonstrated that exposure to childhood adversity is associated with elevated risk for multiple forms of youth psychopathology. In contrast, knowledge of developmental mechanisms linking childhood adversity to the onset of psychopathology-and whether those mechanisms are general or specific to particular kinds of adversity-remains cursory. Greater understanding of these pathways and identification of protective factors that buffer children from developmental disruptions following exposure to adversity is essential to guide the development of interventions to prevent the onset of psychopathology following adverse childhood experiences. This article provides recommendations for future research in this area. In particular, use of a consistent definition of childhood adversity, integration of studies of typical development with those focused on childhood adversity, and identification of distinct dimensions of environmental experience that differentially influence development are required to uncover mechanisms that explain how childhood adversity is associated with numerous psychopathology outcomes (i.e., multifinality) and identify moderators that shape divergent trajectories following adverse childhood experiences. A transdiagnostic model that highlights disruptions in emotional processing and poor executive functioning as key mechanisms linking childhood adversity with multiple forms of psychopathology is presented as a starting point in this endeavour. Distinguishing between general and specific mechanisms linking childhood adversity with psychopathology is needed to generate empirically informed interventions to prevent the long-term consequences of adverse early environments on children's development. PMID- 26849075 TI - Membrane-attached Cytokines Expressed by mRNA Electroporation Act as Potent T Cell Adjuvants. AB - Proinflammatory cytokines are widely explored in different adoptive cell therapy protocols for enhancing survival and function of the transferred T cells, but their systemic administration is often associated with severe toxicity which limits their clinical use. To confine cytokine availability to the therapeutic T cells, we expressed 3 key cytokines, IL-2, IL-12, and IL-15, as integral T-cell membrane proteins. To prevent permanent activation of growth signaling pathways, we delivered these genes to T cells through mRNA electroporation. The engineered cytokines could be detected on the surface of mRNA-transfected cells and binding to their cell-surface receptors mainly occurred in cis. The 3 human cytokines supported the ex vivo growth of activated human CD8 and CD4 T cells for at least 6 days posttransfection, comparably to high-dose soluble IL-2. Similarly, membrane IL-2, membrane IL-12, and, to a lesser extent, membrane IL-15, were comparable with their soluble counterparts in supporting proliferation of splenic mouse CD8 T cells. Following electroporation of human CD8 T cells and antimelanoma tumor-infiltrating lymphocytes, membrane cytokines synergized with constitutively active toll-like receptor 4 in inducing interferon-gamma secretion. Efficient cooperation with TLR4 was also evident in the upregulation of the activation molecules CD25, CD69, CD137 (4-1BB), and CD134 (OX40). Taken together, membrane cytokines expressed through mRNA transfection emerge as effective tools for enhancing T-cell proliferation and function and may have potential use in adoptive T-cell therapy. PMID- 26849077 TI - Expansion of Tumor-reactive T Cells From Patients With Pancreatic Cancer. AB - Generation of T lymphocytes with reactivity against cancer is a prerequisite for effective adoptive cellular therapies. We established a protocol for tumor infiltrating lymphocytes (TILs) from patients with pancreatic ductal adenocarcinoma. Tumor samples from 17 pancreatic cancer specimens were cultured with cytokines (IL-2, IL-15, and IL-21) to expand TILs. After 10 days of culture, TILs were stimulated with an anti-CD3 antibody (OKT3) and irradiated allogeneic peripheral blood mononuclear cells. Reactivity of TILs against tumor-associated antigens (mesothelin, survivin, or NY-ESO-1) was detected by intracellular cytokine production by flow cytometry. Cytotoxicity was measured using a Chromium 51 release assay, and reactivity of TILs against autologous tumor cells was detected by INF-[gamma] production (ELISA). TIL composition was tested by CD45RA, CCR7, 4-1BB, LAG-3, PD-1, TIM3, and CTLA-4 marker analysis. TCR V[beta] was determined by flow cytometry and TCR clonality was gauged measuring the CDR3 region length by PCR analysis and subsequent sequencing. We could reliably obtain TILs from 17/17 patients with a majority of CD8(+) T cells. CD3(+)CD8(+), CD3(+)CD4(+), and CD3(+)CD4(-)CD8(-)[double-negative (DN) T cells] resided predominantly in central (CD45RA(-)CCR7(+)) and effector (CD45RA-CCR7-) memory subsets. CD8(+) TILs tested uniformly positive for LAG-3 (about 100%), whereas CD4(+) TILs showed only up to 12% LAG-3(+) staining and PD-1 showed a broad expression pattern in TILs from different patients. TILs from individual patients recognized strongly (up to 11.9% and 8.2% in CD8(+)) NY-ESO-1, determined by ICS, or mesothelin, determined respectively by TNF-[alpha] and IFN-[gamma] production. Twelve of 17 of CD8(+) TILs showed preferential expansion of certain TCR V[beta] families (eg, 99.2% V[beta]13.2 in CD8(+) TILs, 77% in the V[beta]1, 65.9% in the V[beta]22, and 63.3% in the V[beta]14 family). TCR CDR3 analysis exhibited monoclonal or oligoclonal TCRs, some of them (eg, CD8(+) V[beta]13.2) reacting strongly against autologous tumor defined by INF-[gamma] production or by cytotoxicity. We have optimized methods for generating pancreatic cancer-specific TILs that can be used for adoptive cellular therapy of patients with pancreatic cancer. PMID- 26849076 TI - Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts. AB - Expanding on our prior studies with cord blood T cells, we hypothesized that primary acute myeloid leukemia (AML)-reactive autologous T cells could be generated ex vivo under immunomodulatory conditions. We purified AML and T cells from 8 newly diagnosed high-risk patients. After 2 weeks expansion, T cells were stimulated with interferon-gamma-treated autologous AML weekly * 3, interleukin 15, and agonistic anti-CD28 antibody. Cytotoxic T cells and ELISpot assays tested functionality; reverse transcriptase quantitative polymerase chain reaction tested AML and T-cell gene expression profiles. On the basis of combined positive ELIspot and cytotoxic T cells assays, T cells reactive against AML were generated in 5 of 8 patients. Treg proportion declined after cocultures in reactive T-cell samples. AML-reactive T cells displayed an activated gene expression profile. "Resistant" AML blasts displayed genes associated with immunosuppressive myeloid derived suppressor cells. We discuss our approach to creating primary AML reactive autologous T cell and limitations that require further work. Our study provides a platform for future research targeting on generating autologous leukemia-reactive T cells. PMID- 26849078 TI - Preparation of Cytokine-activated NK Cells for Use in Adoptive Cell Therapy in Cancer Patients: Protocol Optimization and Therapeutic Potential. AB - Cell-based immunotherapy using donor-derived natural killer (NK) cells after allogeneic hematopoietic stem cell transplantation may be an attractive treatment of residual leukemia. This study aimed to optimize clinical grade production of a cytokine-activated NK-cell product. NK cells were isolated either by double depletion (CD3(-), CD19(-)) or by sequential depletion and enrichment (CD3(-,) CD56(+)) via CliniMACS from leukapheresis material and cultured in vitro with interleukin (IL)-2 or IL-15. Both NK cell isolation procedures yielded comparable recovery of NK cells and levels of T-cell contamination. After culture with cytokines, the CD3(-)CD56(+) procedure resulted in NK cells of higher purity, that is, less T cells and monocytes, higher viability, and a slightly higher yield than the CD3(-)CD19- procedure. CD69, NKp44, and NKG2A expression were higher on CD3(-)CD56(+) products, whereas lysis of Daudi cells was comparable. Five days of culture led to higher expression of CD69, NKp44, and NKp30 and lysis of K562 and Daudi cell lines. Although CD69 expression and lysis of Daudi cells were slightly higher in cultures with IL-2, T-cell contamination was lower with IL-15. Therefore, further experiments were performed with CD3(-)CD56(+) products cultured with IL-15. Cryopreservation of IL-15-activated NK cells resulted in a loss of cytotoxicity (>92%), whereas thawing of isolated, uncultured NK cells followed by culture with IL-15 yielded cells with about 43% of the original lytic activity. Five-day IL-15-activated NK cells lysed tumor target cell lines and primary leukemic blasts, providing the basis for NK cell-based immunotherapeutic strategies in a clinical setting. PMID- 26849079 TI - Durable Response to Treatment With Combination Radiotherapy and High-dose Interleukin-2 in Metastatic Chromophobe Variant Renal Cell Carcinoma. AB - This is a report of chromophobe renal cell carcinoma (ChRCC), a rare entity that accounts for 6% to 11% of cases of renal cell carcinoma (RCC). ChRCC is considered to yield a good prognosis as it typically presents as an early stage tumor with longer overall survival when compared with clear cell RCC; however, metastatic disease negates this survival difference and is characterized by poor prognosis. The available clinical investigations supporting the guidelines for treatment of metastatic RCC are predominantly based on clear cell RCC studies. There are no data supporting the applicability of guidelines used to treat clear cell to the management of patients with the ChRCC. This case report describes a male patient who initially presented with locally advanced chromophobe variant RCC, pathologically staged T3aN1M0, initially treated with radical nephrectomy. After developing pathologically confirmed metastatic disease, the patient was treated with repeated cycles of combined hypofractionated radiotherapy to symptomatic metastatic disease sites followed by high-dose intravenous interleukin-2 (HD IL-2) subsequently achieving a near complete and durable response. Three months after initiation of HD IL-2 and radiotherapy, the patient achieved a partial response, and after 6 months he achieved a near complete response. At the time of most recent follow-up, over 36 months after the diagnosis of metastatic disease, the patient remained in remission. On the basis of this experience, we hypothesize that immunomodulation from the radiation potentiated an immune response to HD IL-2 leading to near complete and a durable response in this patient with metastatic ChRCC. PMID- 26849080 TI - Effect of etching with distinct hydrofluoric acid concentrations on the flexural strength of a lithium disilicate-based glass ceramic. AB - This study examined the effects of distinct hydrofluoric acid concentrations on the mechanical behavior of a lithium disilicate-based glass ceramic. Bar-shaped specimens were produced from ceramic blocks (e.max CAD, Ivoclar Vivadent). The specimens were polished, chamfered, and sonically cleaned in distilled water. The specimens were randomly divided into five groups (n = 23). The HF1, HF3, HF5, and HF10 specimens were etched for 20 s with acid concentrations of 1%, 3%, 5%, and 10%, respectively, while the SC (control) sample was untreated. The etched surfaces were evaluated using a scanning electron microscope and an atomic force microscope. Finally, the roughness was measured, and 3-point bending flexural tests were performed. The data were analyzed using one-way analysis of variance (ANOVA) and Tukey's test (alpha = 0.05). The Weibull modulus and characteristic strength were also determined. No statistical difference in the roughness and flexural strength was determined among the groups. The structural reliabilities (Weilbull moduli) were similar for the tested groups; however, the characteristic strength of the HF1 specimen was greater than that of the HF10 specimen. Compared with the untreated ceramic, the surface roughness and flexural strength of the ceramic were unaffected upon etching, regardless of the acid concentration. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 885 891, 2017. PMID- 26849081 TI - Confirmatory factor analysis of the Child Oral Health Impact Profile (Korean version). AB - Empirical support for the factor structure of the Child Oral Health Impact Profile (COHIP) has not been fully established. The purposes of this study were to evaluate the factor structure of the Korean version of the COHIP (COHIP-K) empirically using confirmatory factor analysis (CFA) based on the theoretical framework and then to assess whether any of the factors in the structure could be grouped into a simpler single second-order factor. Data were collected through self-reported COHIP-K responses from a representative community sample of 2,236 Korean children, 8-15 yr of age. Because a large inter-factor correlation of 0.92 was estimated in the original five-factor structure, the two strongly correlated factors were combined into one factor, resulting in a four-factor structure. The revised four-factor model showed a reasonable fit with appropriate inter-factor correlations. Additionally, the second-order model with four sub-factors was reasonable with sufficient fit and showed equal fit to the revised four-factor model. A cross-validation procedure confirmed the appropriateness of the findings. Our analysis empirically supported a four-factor structure of COHIP-K, a summarized second-order model, and the use of an integrated summary COHIP score. PMID- 26849083 TI - Surface lipoproteome of Mycoplasma hominis PG21 and differential expression after contact with human dendritic cells. AB - AIM: To assess the lipoproteins that are involved in the interaction between Mycoplasma hominis and human dendritic cells. MATERIALS & METHODS: The surface lipoproteome of M. hominis PG21 was characterized by using Triton X-114 extraction and LC-MS/MS identification. The transcriptional changes in lipoprotein genes upon contact with human dendritic cells were determined by using reverse transcription quantitative PCR after identification of reference genes suitable for normalization. RESULTS: A large-scale overexpression of lipoprotein genes was observed with 21 upregulated transcripts. Seven genes of unknown function were M. hominis species specific and six genes were putatively associated with increased nutrient capture from the host cell and adhesion. CONCLUSION: M. hominis regulates lipoprotein gene expression and may use species specific mechanisms during the host colonization process. PMID- 26849084 TI - Do Symptoms among Home Palliative Care Patients with Advanced Cancer Decide the Place of Death? Focusing on the Presence or Absence of Symptoms during Home Care. AB - OBJECTIVE: Our goal was to investigate the association between actual place of death among Japanese home end-of-life care patients with advanced cancer and individual, illness, and environmental factors, including the presence or absence of symptoms. METHODS: Using structured interviews, we asked 44 nurses from 19 home-visit nursing agencies about changes in status of all 123 of their home end of-life care patients with advanced cancer between April and September 2013. The main outcome variable was actual place of death (Home/Hospital/Still surviving) and independent variables were the patient's symptoms as a time-dependent variable. Competing risk analysis was conducted with adjustment for patient individual factors (demographics, medical factors, caregiver support, and patient's and caregiver's preference for place of death) and environmental factors (availability of physician-visit and policy at discharge). RESULTS: Among all patients, 53 died in the hospital, 52 at home, and 16 still survived. Multivariate analyses revealed the following: 1) patients were more likely to die in the hospital when pain and dyspnea were present (adjusted sub hazard ratio [SHR]: 1.50 [95% confidence interval (CI): 1.23-1.83] and 1.71 [95% CI: 1.36 2.15], respectively); 2) patients were less likely to die in the hospital when delirium was present (adjusted SHR: 0.64 [95%CI: 0.43-0.96]); and 3) other factors associated with hospital death were patient's gender, primary cancer site, caregiver support, health care service, policy at discharge, and congruence between the patient's and family's preference for place of death. CONCLUSION: To alleviate pain and dyspnea among home end-of-life care patients, development of both a rapid admission system to a hospital/hospice/care facility in the community and specialist-level palliative care at home is needed. PMID- 26849085 TI - Graphene Oxide as an Effective Barrier on a Porous Nanofibrous Membrane for Water Treatment. AB - A novel graphene oxide (GO)-based nanofiltration membrane on a highly porous polyacrylonitrile nanofibrous mat (GO@PAN) is prepared for water treatment applications. GO with large lateral size (more than 200 MUm) is first synthesized through an improved Hummers method and then assembled on a highly porous nanofibrous mat by vacuum suction method. The prepared GO@PAN membrane is characterized by scanning electron microscopy, transmission electron microscopy, Raman spectrum, X-ray diffraction, and so forth. The results show that graphene oxide can form a barrier on the top of a PAN nanofibrous mat with controllable thickness. The obtained graphene oxide layer exhibits "ideal" pathways (hydrophobic nanochannel) for water molecules between the well-stacked GO nanosheets. Water flux under an extremely low external pressure (1.0 bar) significantly increased due to the unique structure of the GO layer and nanofibrous support. Furthermore, the GO@PAN membrane shows high rejection performance (nearly 100% rejection of Congo red and 56.7% for Na2SO4). A hydrophilic-hydrophobic "gate"-nanochannel model is presented for explaining the water diffusion mechanism through the GO layer. This method for fabrication of the GO membrane on a highly porous support may provide many new opportunities for high performance nanofiltration applications. PMID- 26849082 TI - Biologic and clinical characteristics of adolescent and young adult cancers: Acute lymphoblastic leukemia, colorectal cancer, breast cancer, melanoma, and sarcoma. AB - Adolescent and young adult (AYA) patients with cancer have not attained the same improvements in overall survival as either younger children or older adults. One possible reason for this disparity may be that the AYA cancers exhibit unique biologic characteristics, resulting in differences in clinical and treatment resistance behaviors. This report from the biologic component of the jointly sponsored National Cancer Institute and LiveStrong Foundation workshop entitled "Next Steps in Adolescent and Young Adult Oncology" summarizes the current status of biologic and translational research progress for 5 AYA cancers; colorectal cancer breast cancer, acute lymphoblastic leukemia, melanoma, and sarcoma. Conclusions from this meeting included the need for basic biologic, genomic, and model development for AYA cancers as well as translational research studies to elucidate any fundamental differences between pediatric, AYA, and adult cancers. The biologic questions for future research are whether there are mutational or signaling pathway differences (for example, between adult and AYA colorectal cancer) that can be clinically exploited to develop novel therapies for treating AYA cancers and to develop companion diagnostics. PMID- 26849086 TI - The Contributions of Applied Behavior Analysis and Behavior Theory to Innovative Research and Practice Cultures in Social Work. AB - In this article the authors tie the emergence of an empirical practice research culture, which enabled the rise in evidence-based practice in social work to the introduction of applied behavior analysis and behavioral theory to social work practice and research. The authors chronicle the: (1) scientific foundations of social work, (2) influence and push by corporatized university cultures for higher scholarship productivity among faculty, (3) significance of theory in general, (4) importance of behavioral theory in particular as a major trigger of the growth in research on effective social work practice approaches, and (5) commonalities between applied behavior analysis and evidence-based practice. The authors conclude with implications for addressing the dual challenges of building an enhanced research culture in schools of social work and the scholarship of transferring practice research to adoption in real world practice settings. PMID- 26849087 TI - Comparative Study of the Use of Trichloroacetic Acid and Phenolic Acid in the Treatment of Atrophic-Type Acne Scars. AB - BACKGROUND: Many therapies involving varying degrees of complexity have been used to treat acne scars, but none is considered the gold standard treatment. OBJECTIVE: A comparative evaluation of 88% phenol and 90% trichloroacetic acid (TCA) applied using the chemical reconstruction of skin scars (CROSS) technique. MATERIALS AND METHODS: A nonrandomized, single-blinded self-controlled clinical trial was conducted among patients with ice pick-type and boxcar-type atrophic acne scars. Using 88% phenol on the left hemiface and 90% TCA on the right hemiface was adopted as the standard practice of the CROSS technique. The dermatological quality of life index (DLQI) questionnaire, acne scar grading scale Echelle d'Evaluation Clinique des Cicatrices d'Acne (ECCA), and evaluation of improvement were performed pretreatment and post-treatment. RESULTS: Regarding ECCA, significant differences were found in pretreatment and post-treatment (p < .001). Regarding tolerance to pain, it was found that the discomfort felt with 90% TCA was significantly less than that felt with 88% phenol (p = .020). Regarding the quality of life measured with the DLQI, the results showed that the mean score in post-treatment assessment was significantly lower than that in the pretreatment assessment (p < .05). Hypochromia and enlargement scar were only seen after the use of 90% TCA. CONCLUSION: This study confirmed the efficacy of both TCA and phenol for treating such scars, with less severe complications from the use of phenol. PMID- 26849088 TI - Onychocryptosis Treatment Pearls: The "Rolled Cotton Padding" Maneuver and the "Artificial Resin Nail" Technique. PMID- 26849089 TI - Use of Ethyl Chloride in Dermatology Minor Surgery. PMID- 26849090 TI - Double Extramammary Paget Disease of Both the Umbilicus and Scrotum. PMID- 26849091 TI - Reliability of urine lactate as a novel biomarker of lactate production capacity in maximal swimming. AB - CONTEXT: Postexercise urine lactate may be a novel biomarker of lactate production capacity during exercise. OBJECTIVE: To evaluate the reliability and utility of the urine lactate concentration after maximal swimming trials between different training protocols (6 * 50 m and 3 * 100 m) and training states (active and nonactive swimmers). MATERIALS AND METHODS: Lactate and creatinine were determined by spectrophotometry in blood and urine. RESULTS: Blood and urine lactate concentrations were correlated in-between training protocols and in participants of different training states. The reliability of the urine lactate concentration was moderate for one of the training protocols and good or moderate for the two training states. Additionally, it was lower than that of the blood lactate concentration, and did not improve after normalizing to the urine creatinine concentration. DISCUSSION AND CONCLUSION: Although promising as a biomarker of lactate production capacity, urine lactate requires further research to improve its reliability. PMID- 26849092 TI - Probiotic and functional characterization of bifidobacteria of Indian human origin. AB - AIMS: To identify and characterize the probiotic and functional attributes of bifidobacteria isolated from human sources by in vitro methods. METHODS AND RESULTS: Twelve isolates of bifidobacteria were obtained from different human sources viz; human milk, infant and adult faeces. The preliminary identification of isolates was done using genus-specific PCR followed by species level identification using 16S rRNA sequencing. All the isolates invariably showed potential probiotic characteristics. Finally, three most promising isolates were subjected to safety evaluation and were found to be safe. These were further evaluated for their potential functional characteristics like, antioxidative, antimutagenic and cholesterol assimilation. The isolates viz; NBIF-5 (73.55 +/- 0.03%) and NBIF-7 (64.06 +/- 0.03%) assimilated significantly higher cholesterol than NBIF-2. The maximum antioxidative activity was observed in NBIF-2 (56.56 +/- 0.28% of radical inhibition). High percentage antimutagenicity scores of 52.41 +/ 2.25% and 53.68 +/- 1.98% against sodium azide (NaN3) were shown by NBIF-2 and NBIF-7 respectively. CONCLUSIONS: Three strains (NBIF-2, NBIF-5 and NBIF-7) were found to be endowed with appreciable probiotic and functional activities. SIGNIFICANCE AND IMPACT OF THE STUDY: With growing demands for probioitcs and bifidobacteria being prominent ones, new strains of diversified origin have the potential to be explored for commercial and functional applications and thus can be added to the existing commercially available strains of this genera. PMID- 26849093 TI - Vitamin D Status in Pregnancy and Determinants in a Southern European Cohort Study. AB - BACKGROUND: Population-based data on vitamin D status in pregnancy in southern European countries are scarce. We assessed the prevalence and determinants of vitamin D insufficiency and deficiency in pregnancy in Spain. METHODS: Plasma 25 hydroxyvitamin D3 (25(OH)D3) concentration was measured at the first trimester of gestation in 2,036 pregnant women from several geographical areas of Spain (latitude 39-42 degrees N). Uni- and multivariable regression models were conducted to identify predictors of circulating 25(OH)D3 concentration and vitamin D insufficiency (20-30 ng/mL) and deficiency (<20 ng/mL). RESULTS: Thirty one per cent and 18% of women were vitamin D insufficient and deficient, respectively. Season at blood collection, latitude, age, social class, tobacco smoking, physical activity and use of vitamin D supplements were identified as independent determinants of 25(OH)D3 concentration. Lower risk of vitamin D insufficiency and deficiency was associated with summer season at blood collection (RR for insufficiency = 0.34, confidence intervals (CI) 0.25, 0.48; and RR for deficiency = 0.07, 95% CI 0.04, 0.12), southern latitude (RR for insufficiency = 0.71, 95% CI 0.50, 1.02; RR for deficiency = 0.60, 95% CI 0.38, 0.94); use of vitamin D supplements (RR for insufficiency = 0.50, 95% CI 0.35, 0.71; RR for deficiency = 0.24, 95% CI 0.14, 0.41); and strong physical activity (RR for insufficiency = 0.80, 95% CI 0.58, 1.09; and RR for deficiency = 0.67, 95% CI 0.46, 1.03). Higher risk of vitamin D deficiency was related to lower social class (RR = 1.94, 95% CI 1.19, 3.16) and smoking (RR = 1.76, 95% CI 1.23, 2.54). CONCLUSIONS: Vitamin D insufficiency and deficiency are highly prevalent in pregnancy. Recommendations and policies to detect and prevent hypovitaminosis D during pregnancy should be developed taking into account the associated factors. PMID- 26849094 TI - A randomised cross-over trial comparing the McGrath((r)) Series 5 videolaryngoscope with the Macintosh laryngoscope in patients with cervical spine immobilisation. AB - We compared the performance of the McGrath(r) Series 5 videolaryngoscope with the Macintosh laryngoscope in 49 patients without suspected cervical spine pathology, whose cervical spine was immobilised using a semi-rigid collar. The primary outcome was the view obtained at laryngoscopy. Secondary outcomes included time to tracheal intubation, rates of successful intubation and incidence of complications. In all patients, the view was better (92%) or the same (8%) in the McGrath group versus the Macintosh group (p < 0.01). There were no failed intubations in the McGrath group and seven (28%) in the Macintosh group (p < 0.02). There was no statistical difference in time taken to intubate or incidence of complications. We conclude that the McGrath(r) Series 5 is a superior laryngoscope when cervical spine immobilisation is maintained during tracheal intubation. PMID- 26849096 TI - Precisely Controlled Ultrathin Conjugated Polymer Films for Large Area Transparent Transistors and Highly Sensitive Chemical Sensors. AB - A uniform ultrathin polymer film is deposited over a large area with molecularlevel precision by the simple wire-wound bar-coating method. The bar coated ultrathin films not only exhibit high transparency of up to 90% in the visible wavelength range but also high charge carrier mobility with a high degree of percolation through the uniformly covered polymer nanofibrils. They are capable of realizing highly sensitive multigas sensors and represent the first successful report of ethylene detection using a sensor based on organic field effect transistors. PMID- 26849099 TI - Endoscopic ultrasound-guided antegrade treatment of bile duct stone in patients with surgically altered anatomy: a multicenter retrospective cohort study. AB - BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) for management of bile duct stone (BDS) in patients with surgically altered anatomy is challenging even when applying enteroscopy. Endoscopic ultrasound-guided antegrade treatments (EUS-AG) for BDS have been developed but have not been well studied yet. The aim of the present study was to evaluate the feasibility and safety of EUS-AG for BDS in patients with surgically altered anatomy as a multicenter retrospective cohort study. METHODS: A retrospective database analysis was performed to identify patients with surgically altered anatomy who underwent EUS-AG for the management of BDS at four academic care centers. Basic characteristics of the patients and details of the procedures were determined and the success rates and adverse event rates were evaluated. RESULTS: EUS-AG for BDS was attempted in 29 patients. Successful BDS removal was achieved in 72% (21/29) of patients. Reasons for failed EUS-AG were unsuccessful bile duct puncture in six, unsuccessful guidewire manipulation in one, and unsuccessful stone removal using a retrieval balloon in one. Adverse events occurred in five (17%) but were successfully managed conservatively. CONCLUSION: EUS-AG for BDS is a feasible and safe alternative in patients with surgically altered anatomy, although further evaluation and development of dedicated devices are needed. PMID- 26849100 TI - Estrous cycle synchronization in the Persian onager (Equus hemionus onager). AB - The endangered Persian onager (Equus hemionus onager) has experienced significant population declines over the past century due to poaching, habitat destruction, and resource competition. Remaining animals in zoos and the wild are regionally isolated. Artificial insemination (AI) may be particularly useful as a means of aiding in global genetic management of these isolated populations. The first successful AI in onagers was performed in 2009 utilizing urinary hormone analyses and regular transrectal ultrasound examinations that required specialized handling devices. A method for estrous synchronization in this species would alleviate the need for daily handling and provide a more feasible approach to AI. This study tested long-acting controlled-release preparations of estradiol and progesterone, followed by a single injection of prostaglandin 10 days later, in six adult female Persian onagers to determine whether ovulation would occur within a narrow window of time. Serial transrectal ultrasound exams were performed to determine the day of ovulation following hormone treatment. Means and standard deviations were determined for the lengths of follicular and luteal phases, follicle sizes, and time to ovulation, and compared to historical data in this species. All six onagers ovulated between Days 18 and 22, with three females ovulating on Day 19, as determined by the presence of a corpus luteum. This is an apparently safe and effective method for the synchronization of estrous cycles in the Persian onager, and may be used to develop a timed AI protocol for use at institutions that do not have specialized handling facilities to enable regular transrectal ultrasound. PMID- 26849095 TI - Fibroblast growth factor family aberrations as a putative driver of head and neck squamous cell carcinoma in an epidemiologically low-risk patient as defined by targeted sequencing. AB - BACKGROUND: Targeted sequencing of patients with epidemiologically low-risk (ELR) head and neck squamous cell carcinoma (HNSCC) could help identify novel drivers or lost suppressors leading to precision medicine protocols and improved survival rates. METHODS: A patient with ELR-HNSCC was selected for targeted sequencing. We then assessed next generation sequencing cohorts from the Oncomine Powertool Database, which contains pan-cancer data from The Cancer Genome Atlas (TCGA). RESULTS: Targeted sequencing revealed fibroblast growth factor receptor-1 (FGFR1) amplifications as a putative driver of the patient's tumor. Patients with HNSCC from TCGA data demonstrated fibroblast growth factor (FGF) family mutations, rearrangements, or amplifications in over 35% of HNSCC cases, with a statistically significant higher frequency in African American populations. FGF alterations were unique from activating phosphatidylinositol 3-kinase (PIK3CA) mutations. CONCLUSION: Together, these data suggest that FGF signaling may be critical for a subset of patients with HNSCC independent of other known pathways and provides rationale for leveraging patients with ELR-HNSCC to define molecular subsets of high-risk HNSCC. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1646 E1652, 2016. PMID- 26849101 TI - Modeling event-related heart period responses. AB - Cardiac rhythm is generated locally in the sinoatrial node, but modulated by central neural input. This may provide a possibility to infer central processes from observed phasic heart period responses (HPR). Currently, operational methods are used for HPR analysis. These methods embody implicit assumptions on how central states influence heart period. Here, we build an explicit psychophysiological model (PsPM) for event-related HPR. This phenomenological PsPM is based on three experiments involving white noise sounds, an auditory oddball task, and emotional picture viewing. The model is optimized with respect to predictive validity-the ability to separate experimental conditions from each other. To validate the PsPM, an independent sample of participants is presented with auditory stimuli of varying intensity and emotional pictures of negative and positive valence, at short intertrial intervals. Our model discriminates these experimental conditions from each other better than operational approaches. We conclude that our PsPM is more sensitive to distinguish experimental manipulations based on heart period data than operational methods, and furnishes a principled approach to analysis of HPR. PMID- 26849102 TI - Influence of Veneering Fabrication Techniques and Gas-Phase Fluorination on Bond Strength between Zirconia and Veneering Ceramics. AB - PURPOSE: Porcelain chipping has been one of the main problems of porcelain-fused to-zirconia restorations. This study evaluates the bond strengths of layered, pressed, and adhesively bonded porcelain to yttria-stabilized zirconia substrates that have undergone traditional preparation or gas-phase fluorination. MATERIALS AND METHODS: A three-point bending test was used to evaluate the bond strength of the porcelain and zirconia interface. Sixty-six specimens were prepared (n = 11) following ISO 9693 and loaded until failure using an Instron testing machine. One half of the zirconia substrates received gas phase fluorination treatment before veneering application. Three porcelain veneering methods were evaluated: layered, pressed, and adhesively bonded porcelain. Bond strength results were interpreted using a two-way ANOVA and a Bonferroni multiple comparisons test. Statistical significance was set at alpha = 0.05. RESULTS: ANOVA revealed a statistically significant effect of the veneering fabrication methods. No main effect was observed regarding the surface treatment to the zirconia. There was a significant effect related to the veneering method used to apply porcelain to zirconia. For untreated zirconia, layered porcelain had a significantly higher flexural strength compared to pressed or bonded, while pressed and bonded porcelains were not significantly different from one another. For zirconia specimens receiving fluorination treatment, both layered and pressed porcelains had significantly higher bond strengths than adhesively bonded porcelain. In addition, fluorinated pressed porcelain was not statistically different from the control layered or fluorinated layered porcelain. CONCLUSION: The choice of veneering fabrication technique was critical when evaluating the zirconia to porcelain interfacial bond strength. Bonded porcelain to zirconia had a lower flexural strength than layered or pressed porcelain, regardless of zirconia surface treatment. In addition, fluorination had an effect on the bond strength of pressed porcelain. PMID- 26849103 TI - US Navy Women's Experience of an Abnormal Cervical Cancer Screening. AB - INTRODUCTION: Recent policy revisions allow greater inclusion of military women in operational and/or deployable positions (ie, shipboard, overseas, and war zone duty assignments), but these positions can create unique health care challenges. Military members are often transient due to deployments and change of duty stations, impacting timely follow-up care for treatable health conditions. There has been minimal research on challenges or strategies in preventive health screening and follow-up for US military women. METHODS: The purpose of this qualitative research study was to describe US Navy women's experiences with abnormal cervical cancer screenings requiring colposcopic follow-up care. Ship- and shored-based women receiving care at a military colposcopy clinic completed interviews about their experience. Two forms of narrative analysis, Labov's sociolinguistic structural analysis and Braun and Clarke's thematic analysis, were employed to gain a more robust understanding of the women's experiences. RESULTS: The sample was comprised of 26 women (16 ship-based, 10 shore-based). Five themes were identified: 1) It's like this bombshell (initial abnormal results notification); 2) I didn't understand (self-discovery process); 3) Freaked (emotional toll); 4) It's kind of like this back and forth (scheduling and navigating care); and 5) It really opened my eyes (lessons learned). DISCUSSION: The women's stories highlighted some issues unique to military health care, such as operational demands and follow-up care; other issues are likely common for most women learning about an abnormal cervical cancer screening result. Areas important for practice and future research include improving notification practices, providing information, understanding women's fear, and continuity of care. Research exploring educational initiatives and self management practices are critical within military populations. PMID- 26849105 TI - Ordered Mesoporous Cobalt Phosphate with Crystallized Walls toward Highly Active Water Oxidation Electrocatalysts. AB - A hexagonally ordered mesoporous cobalt phosphate (CoPi) material is prepared by a facile one-pot soft-templating strategy using cetyltrimethylammonium bromide template. Because of its highly accessible surface area and crystalline framework with abundant active sites, the mesoporous CoPi shows a high catalytic activity for the oxygen evolution reaction compared to previously reported noble/transition-metal and nonmetal catalysts. PMID- 26849104 TI - Nanosuspension formulations of poorly water-soluble compounds for intravenous administration in exploratory toxicity studies: in vitro and in vivo evaluation. AB - This study was conducted to investigate the use of a nanosuspension for intravenous injection into dogs to increase exposure without toxic additives for preclinical studies in the discovery stage. Nanosuspensions were prepared with a mixer mill and zirconia beads with a vehicle of 2% (w/v) poloxamer 338, which was confirmed to lead to no histamine release in dogs. Sterilized nanosuspensions of poorly water-soluble compounds, cilostazol (Cil), spironolactone (Spi) and probucol (Pro), at 10 mg ml(-1) were obtained by milling for 30 min, followed by autoclaving for 20 min at 121 degrees C and milling for 30 min (mill-autoclave mill method). The particle sizes (d50) of Cil, Spi and Pro were 0.554, 0.484 and 0.377 um, respectively, and the percentages of the nominal concentration were 79.1%, 99.6% and 75.4%, respectively. In chromatographic data, no extra peaks were observed. The particle size of Cil was 0.564 um after storage for 16 days at 2-8 degrees C. Cil in nanosuspension, but not in microsuspension, rapidly dissolved in dog plasma. Cil nanosuspension at 0.4 mg kg(-1) and Cil saline solution at 0.03 mg kg(-1) , around the saturation solubility, were intravenously administered to dogs. Nanosuspension increased exposure. The versatility of the mill-autoclave-mill method was checked for 15 compounds, and the particle size of 12 compounds was in the nano range. The nanosuspension optimized in this study may be useful for intravenous toxicological and pharmacological studies in the early stage of drug development. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26849106 TI - Cardiac ryanodine receptor: Selectivity for alkaline earth metal cations points to the EF-hand nature of luminal binding sites. AB - A growing body of evidence suggests that the regulation of cardiac ryanodine receptor (RYR2) by luminal Ca(2+) is mediated by luminal binding sites located on the RYR2 channel itself and/or its auxiliary protein, calsequestrin. The localization and structure of RYR2-resident binding sites are not known because of the lack of a high-resolution structure of RYR2 luminal regions. To obtain the first structural insight, we probed the RYR2 luminal face stripped of calsequestrin by alkaline earth metal divalents (M(2+): Mg(2+), Ca(2+), Sr(2+) or Ba(2+)). We show that the RYR2 response to caffeine at the single-channel level is significantly modified by the nature of luminal M(2+). Moreover, we performed competition experiments by varying the concentration of luminal M(2+) (Mg(2+), Sr(2+) or Ba(2+)) from 8 mM to 53 mM and investigated its ability to compete with 1mM luminal Ca(2+). We demonstrate that all tested M(2+) bind to exactly the same RYR2 luminal binding sites. Their affinities decrease in the order: Ca(2+)>Sr(2+)>Mg(2+)~Ba(2+), showing a strong correlation with the M(2+) affinity of the EF-hand motif. This indicates that the RYR2 luminal binding regions and the EF-hand motif likely share some structural similarities because the structure ties directly to the function. PMID- 26849107 TI - Genomewide single nucleotide polymorphism discovery in Atlantic salmon (Salmo salar): validation in wild and farmed American and European populations. AB - A considerable number of single nucleotide polymorphisms (SNPs) are required to elucidate genotype-phenotype associations and determine the molecular basis of important traits. In this work, we carried out de novo SNP discovery accounting for both genome duplication and genetic variation from American and European salmon populations. A total of 9 736 473 nonredundant SNPs were identified across a set of 20 fish by whole-genome sequencing. After applying six bioinformatic filtering steps, 200 K SNPs were selected to develop an Affymetrix Axiom((r)) myDesign Custom Array. This array was used to genotype 480 fish representing wild and farmed salmon from Europe, North America and Chile. A total of 159 099 (79.6%) SNPs were validated as high quality based on clustering properties. A total of 151 509 validated SNPs showed a unique position in the genome. When comparing these SNPs against 238 572 markers currently available in two other Atlantic salmon arrays, only 4.6% of the SNP overlapped with the panel developed in this study. This novel high-density SNP panel will be very useful for the dissection of economically and ecologically relevant traits, enhancing breeding programmes through genomic selection as well as supporting genetic studies in both wild and farmed populations of Atlantic salmon using high-resolution genomewide information. PMID- 26849108 TI - Cardiovascular, respiratory and metabolic responses to apnea induced by atlanto occipital intrathecal lidocaine injection in anesthetized horses. AB - OBJECTIVE: To determine physiologic responses to apnea-induced severe hypoxemia in anesthetized horses. STUDY DESIGN: Prospective experimental study. ANIMALS: Six university-owned horses with a median (range) body weight of 500 (220-510) kg and aged 13.5 (0.8-24.0) years scheduled for euthanasia. METHODS: Xylazine midazolam-ketamine-anesthetized horses breathing room air spontaneously were instrumented with a facial artery catheter for pressure measurement and blood sampling, and were made apneic with atlanto-occipital intrathecal lidocaine (4 mg kg-1 ). Cardiopulmonary, biochemical and hematologic variables were recorded before (baseline) and every minute for 10 minutes after lidocaine injection. RESULTS: PaO2 values were: baseline, 55 mmHg (7.3 kPa); 1 minute, 28 mmHg (3.8 kPa); 2 minutes, 18 mmHg (2.4 kPa); 3 minutes, 15 mmHg (2.0 kPa), and 4-10 minutes, (8-11 mmHg (1.1-1.5 kPa). PaCO2 values were: baseline, 50 mmHg (6.7 kPa); 1 minute, 61 mmHg (8.1 kPa), and 2-10 minutes, 64-66 mmHg (8.5-8.8 kPa). Base excess values at baseline, 1 minute and 2-10 minutes were 5.3 mmol L-1 , 6.5 mmol L-1 and 7.0-8.1 mmol L-1 , respectively. Pulse rates at baseline, 1 minute and 2-7 minutes were 36, 53 and 54-85 beats minute-1 , respectively. Asystole occurred at 8 minutes. Pulse pressures were 50 mmHg at baseline and 1 minute, and 39 mmHg, 31 mmHg, 22 mmHg, 17 mmHg and 1-9 mmHg at 2, 3, 4, 5 and 6-10 minutes, respectively. Lactate was 0.9 mmol L-1 at baseline, progressively increasing to 1.7-2.4 mmol L-1 at 7-10 minutes. Packed cell volume increased after 7 minutes of apnea. There were no other major changes. CONCLUSIONS AND CLINICAL RELEVANCE: Apnea immediately exacerbated hypoxemia and hypercapnia and rapidly caused hemodynamic instability. Apnea in hypoxemic anesthetized horses is associated with a serious risk for progress to cardiovascular collapse. PMID- 26849109 TI - Loss of miR-182 affects B-cell extrafollicular antibody response. AB - MicroRNAs have been shown to play a role in B-cell differentiation and activation. Here, we found miR-182 to be highly induced in activated B cells. However, mice lacking miR-182 have normal B-cell and T-cell development. Interestingly, mutant mice exhibited a defective antibody response at early time points in the immunization regimen when challenged with a T-cell-dependent antigen. Germinal centres were formed but the generation of extrafollicular plasma cells was defective in the spleens of immunized miR-182-deficient mice. Mutant mice were also not able to respond to a T-cell-independent type 2 antigen, which typically elicited an extrafollicular B-cell response. Taken together, the data indicated that miR-182 plays a critical role in driving extrafollicular B cell antibody responses. PMID- 26849110 TI - ZNF687 Mutations in Severe Paget Disease of Bone Associated with Giant Cell Tumor. AB - Paget disease of bone (PDB) is a skeletal disorder characterized by focal abnormalities of bone remodeling, which result in enlarged and deformed bones in one or more regions of the skeleton. In some cases, the pagetic tissue undergoes neoplastic transformation, resulting in osteosarcoma and, less frequently, in giant cell tumor of bone (GCT). We performed whole-exome sequencing in a large family with 14 PDB-affected members, four of whom developed GCT at multiple pagetic skeletal sites, and we identified the c.2810C>G (p.Pro937Arg) missense mutation in the zinc finger protein 687 gene (ZNF687). The mutation precisely co segregated with the clinical phenotype in all affected family members. The sequencing of seven unrelated individuals with GCT associated with PDB (GCT/PDB) identified the same mutation in all individuals, unravelling a founder effect. ZNF687 is highly expressed during osteoclastogenesis and osteoblastogenesis and is dramatically upregulated in the tumor tissue of individuals with GCT/PDB. Interestingly, our preliminary findings showed that ZNF687, indicated as a target gene of the NFkB transcription factor by ChIP-seq analysis, is also upregulated in the peripheral blood of PDB-affected individuals with (n = 5) or without (n = 6) mutations in SQSTM1, encouraging additional studies to investigate its potential role as a biomarker of PDB risk. PMID- 26849111 TI - The HTT CAG-Expansion Mutation Determines Age at Death but Not Disease Duration in Huntington Disease. AB - Huntington disease (HD) is caused by an expanded HTT CAG repeat that leads in a length-dependent, completely dominant manner to onset of a characteristic movement disorder. HD also displays early mortality, so we tested whether the expanded CAG repeat exerts a dominant influence on age at death and on the duration of clinical disease. We found that, as with clinical onset, HD age at death is determined by expanded CAG-repeat length and has no contribution from the normal CAG allele. Surprisingly, disease duration is independent of the mutation's length. It is also unaffected by a strong genetic modifier of HD motor onset. These findings suggest two parsimonious alternatives. (1) HD pathogenesis is driven by mutant huntingtin, but before or near motor onset, sufficient CAG driven damage occurs to permit CAG-independent processes and then lead to eventual death. In this scenario, some pathological changes and their clinical correlates could still worsen in a CAG-driven manner after disease onset, but these CAG-related progressive changes do not themselves determine duration. Alternatively, (2) HD pathogenesis is driven by mutant huntingtin acting in a CAG dependent manner with different time courses in multiple cell types, and the cellular targets that lead to motor onset and death are different and independent. In this scenario, processes driven by HTT CAG length lead directly to death but not via the striatal pathology associated with motor manifestations. Each scenario has important ramifications for the design and testing of potential therapeutics, especially those aimed at preventing or delaying characteristic motor manifestations. PMID- 26849112 TI - A Burden of Rare Variants Associated with Extremes of Gene Expression in Human Peripheral Blood. AB - In order to evaluate whether rare regulatory variants in the vicinity of promoters are likely to impact gene expression, we conducted a novel burden test for enrichment of rare variants at the extremes of expression. After sequencing 2 kb promoter regions of 472 genes in 410 healthy adults, we performed a quadratic regression of rare variant count on bins of peripheral blood transcript abundance from microarrays, summing over ranks of all genes. After adjusting for common eQTLs and the major axes of gene expression covariance, a highly significant excess of variants with minor allele frequency less than 0.05 at both high and low extremes across individuals was observed. Further enrichment was seen in sites annotated as potentially regulatory by RegulomeDB, but a deficit of effects was associated with known metabolic disease genes. The main result replicates in an independent sample of 75 individuals with RNA-seq and whole-genome sequence information. Three of four predicted large-effect sites were validated by CRISPR/Cas9 knockdown in K562 cells, but simulations indicate that effect sizes need not be unusually large to produce the observed burden. Unusually divergent low-frequency promoter haplotypes were observed at 31 loci, at least 9 of which appear to be derived from Neandertal admixture, but these were not associated with divergent gene expression in blood. The overall burden test results are consistent with rare and private regulatory variants driving high or low transcription at specific loci, potentially contributing to disease. PMID- 26849113 TI - Disease and Polygenic Architecture: Avoid Trio Design and Appropriately Account for Unscreened Control Subjects for Common Disease. AB - Genome-wide association studies (GWASs) are an optimal design for discovery of disease risk loci for diseases whose underlying genetic architecture includes many common causal loci of small effect (a polygenic architecture). We consider two designs that deserve careful consideration if the true underlying genetic architecture of the trait is polygenic: parent-offspring trios and unscreened control subjects. We assess these designs in terms of quantification of the total contribution of genome-wide genetic markers to disease risk (SNP heritability) and power to detect an associated risk allele. First, we show that trio designs should be avoided when: (1) the disease has a lifetime risk > 1%; (2) trio probands are ascertained from families with more than one affected sibling under which scenario the SNP heritability can drop by more than 50% and power can drop as much as from 0.9 to 0.15 for a sample of 20,000 subjects; or (3) assortative mating occurs (spouse correlation of the underlying liability to the disorder), which decreases the SNP heritability but not the power to detect a single locus in the trio design. Some studies use unscreened rather than screened control subjects because these can be easier to collect; we show that the estimated SNP heritability should then be scaled by dividing by (1 - K * u)(2) for disorders with population prevalence K and proportion of unscreened control subjects u. When omitting to scale appropriately, the SNP heritability of, for example, major depressive disorder (K = 0.15) would be underestimated by 28% when none of the control subjects are screened. PMID- 26849114 TI - A Robust Example of Collider Bias in a Genetic Association Study. PMID- 26849115 TI - Response to Day et al. PMID- 26849116 TI - The Kalash Genetic Isolate? The Evidence for Recent Admixture. PMID- 26849117 TI - Response to Hellenthal et al. PMID- 26849118 TI - Conservative strategy in infantile fibrosarcoma is possible: The European paediatric Soft tissue sarcoma Study Group experience. AB - BACKGROUND: Infantile fibrosarcoma (IFS) is a very rare disease occurring in young infants characterised by a high local aggressiveness but overall with a favourable survival. To try to reduce the total burden of therapy, the European pediatric Soft tissue sarcoma Study Group has developed conservative therapeutic recommendations according to initial resectability. MATERIAL AND METHODS: Between 2005 and 2012, children with localised IFS were prospectively registered. Initial surgery was suggested only if possible without mutilation. Patients with initial complete (IRS-group I/R0) or microscopic incomplete (group II/R1) resection had no further therapy. Patients with initial inoperable tumour (group III/R2) received first-line vincristine-actinomycin-D chemotherapy (VA). Delayed conservative surgery was planned after tumour reduction. Aggressive local therapy (mutilating surgery or external radiotherapy) was discouraged. RESULTS: A total of 50 infants (median age 1.4 months), were included in the study. ETV6-NTRK3 transcript was present in 87.2% of patients where investigation was performed. According to initial surgery, 11 patients were classified as group I, 8 as group II and 31 as group III. VA chemotherapy was first delivered to 25 children with IRS-III/R2 and one with IRS-II/R1 disease. Response rate to VA was 68.0%. Mutilating surgery was only performed in three cases. After a median follow-up of 4.7 years (range 1.9-9.0), 3-year event-free survival and overall survival were respectively 84.0% (95% confidence interval [CI] 70.5-91.7) and 94.0% (95% CI 82.5-98.0). CONCLUSIONS: Conservative therapy is possible in IFS as only three children required mutilating surgery, and alkylating or anthracycline based chemotherapy was avoided in 71.0% of patients needing chemotherapy. VA regimen should be first line therapy in order to reduce long term effects. PMID- 26849121 TI - Atmospheric Mercury Transfer to Peat Bogs Dominated by Gaseous Elemental Mercury Dry Deposition. AB - Gaseous elemental mercury (GEM) is the dominant form of mercury in the atmosphere. Its conversion into oxidized gaseous and particulate forms is thought to drive atmospheric mercury wet deposition to terrestrial and aquatic ecosystems, where it can be subsequently transformed into toxic methylmercury. The contribution of mercury dry deposition is however largely unconstrained. Here we examine mercury mass balance and mercury stable isotope composition in a peat bog ecosystem. We find that isotope signatures of living sphagnum moss (Delta(199)Hg = -0.11 +/- 0.090/00, Delta(200)Hg = 0.03 +/- 0.020/00, 1sigma) and recently accumulated peat (Delta(199)Hg = -0.22 +/- 0.060/00, Delta(200)Hg = 0.00 +/- 0.040/00, 1sigma) are characteristic of GEM (Delta(199)Hg = -0.17 +/- 0.070/00, Delta(200)Hg = -0.05 +/- 0.020/00, 1sigma), and differs from wet deposition (Delta(199)Hg = 0.73 +/- 0.150/00, Delta(200)Hg = 0.21 +/- 0.040/00, 1sigma). Sphagnum covered during three years by transparent and opaque surfaces, which eliminate wet deposition, continue to accumulate Hg. Sphagnum Hg isotope signatures indicate accumulation to take place by GEM dry deposition, and indicate little photochemical re-emission. We estimate that atmospheric mercury deposition to the peat bog surface is dominated by GEM dry deposition (79%) rather than wet deposition (21%). Consequently, peat deposits are potential records of past atmospheric GEM concentrations and isotopic composition. PMID- 26849119 TI - Antioxidant Carbocysteine Treatment in Obstructive Sleep Apnea Syndrome: A Randomized Clinical Trial. AB - OBJECTIVE: This study aimed to examine the effects of carbocysteine in OSAS patients. METHODS: A total of 40 patients with moderate to severe obstructive sleep apnea syndrome (OSAS) were randomly divided into two groups. One group was treated with 1500 mg carbocysteine daily, and the other was treated with continuous positive airway pressure (CPAP) at night. Before treatment and after 6 weeks of treatment, all patients underwent polysomnography and completed questionnaires. Treatment compliance was compared between the two groups. Plasma was collected for various biochemical analyses. Endothelial function was assessed with ultrasound in the carbocysteine group. RESULTS: The proportion of patients who fulfilled the criteria for good compliance was higher in the carbocysteine group (n = 17) than in the CPAP group (n = 11; 100% vs. 64.7%). Compared with baseline values, the carbocysteine group showed significant improvement in their Epworth Sleepiness Scale score (10.18 +/- 4.28 vs. 6.82 +/- 3.66; P <= 0.01), apnea-hypopnea index (55.34 +/- 25.03 vs. 47.56 +/- 27.32; P <= 0.01), time and percentage of 90% oxygen desaturation (12.66 (2.81; 50.01) vs. 8.9 (1.41; 39.71); P <= 0.01), and lowest oxygen saturation level (65.88 +/- 14.86 vs. 70.41 +/- 14.34; P <= 0.01). Similar changes were also observed in the CPAP group. The CPAP group also showed a decreased oxygen desaturation index and a significant increase in the mean oxygen saturation after treatment, but these increases were not observed in the carbocysteine group. Snoring volume parameters, such as the power spectral density, were significantly reduced in both groups after the treatments. The plasma malondialdehyde level decreased and the superoxide dismutase and nitric oxide levels increased in both groups. The endothelin-1 level decreased in the CPAP group but did not significantly change in the carbocysteine group. Ultrasonography showed that the intima-media thickness decreased (0.71 +/- 0.15 vs. 0.66 +/- 0.15; P <= 0.05) but that flow-mediated dilation did not significantly change in the carbocysteine group. CONCLUSIONS: Oral carbocysteine slightly improves sleep disorders by attenuating oxidative stress in patients with moderate to severe OSAS. Carbocysteine may have a role in the treatment of OSAS patients with poor compliance with CPAP treatment. However, the efficiency and feasibility of carbocysteine treatment for OSAS needs further evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT02015598. PMID- 26849122 TI - Correction: Comparison of Unplanned Intensive Care Unit Readmission Scores: A Prospective Cohort Study. PMID- 26849120 TI - Forest Gaps Alter the Total Phenol Dynamics in Decomposing Litter in an Alpine Fir Forest. AB - The total phenol content in decomposing litter not only acts as a crucial litter quality indicator, but is also closely related to litter humification due to its tight absorption to clay particles. However, limited attention has been focused on the total phenol dynamics in foliar litter in relation to forest gaps. Here, the foliar litter of six representative tree species was incubated on the forest floor from the gap center to the closed canopy of an alpine Minjiang fir (Abies faxoniana) forest in the upper reaches of the Yangtze River and eastern Tibetan Plateau. The dynamics of total phenol concentration in the incubated litter was measured from November 2012 to October 2014. Over two-year incubation, 78.22% to 94.06% of total phenols were lost from the foliar litter, but 52.08% to 86.41% of this occurred in the first year. Forest gaps accelerated the loss of total phenols in the foliar litter in the winter, although they inhibited the loss of total phenols during the growing season in the first year. In comparison with the effects of forest gaps, the variations of litter quality among different species were much stronger on the dynamics of total phenols in the second year. Overall, the loss of total phenols in the foliar litter was slightly higher in both the canopy gap and the expanded gap than in the gap center and under the closed canopy. The results suggest that the predicted decline in snow cover resulting from winter warming or vanishing gaps caused by forest regeneration will retard the loss of total phenol content in the foliar litter of alpine forest ecosystems, especially in the first decomposition year. PMID- 26849123 TI - An Adaptive Ridge Procedure for L0 Regularization. AB - Penalized selection criteria like AIC or BIC are among the most popular methods for variable selection. Their theoretical properties have been studied intensively and are well understood, but making use of them in case of high dimensional data is difficult due to the non-convex optimization problem induced by L0 penalties. In this paper we introduce an adaptive ridge procedure (AR), where iteratively weighted ridge problems are solved whose weights are updated in such a way that the procedure converges towards selection with L0 penalties. After introducing AR its specific shrinkage properties are studied in the particular case of orthogonal linear regression. Based on extensive simulations for the non-orthogonal case as well as for Poisson regression the performance of AR is studied and compared with SCAD and adaptive LASSO. Furthermore an efficient implementation of AR in the context of least-squares segmentation is presented. The paper ends with an illustrative example of applying AR to analyze GWAS data. PMID- 26849125 TI - The Association of Mycobacterium avium subsp. paratuberculosis with Inflammatory Bowel Disease. AB - The association of Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) with Crohn's disease is a controversial issue. M. paratuberculosis is detected by amplifying the IS900 gene, as microbial culture is unreliable from humans. We determined the presence of M. paratuberculosis in patients with Crohn's disease (CD) (n = 22), ulcerative colitis (UC) (n = 20), aphthous ulcers (n = 21) and controls (n = 42) using PCR assays validated on bovine tissue. Culture from human tissue was also performed. M. paratuberculosis prevalence in the CD and UC groups was compared to the prevalence in age and sex matched non-inflammatory bowel disease controls. Patients and controls were determined to be M. paratuberculosis positive if all three PCR assays were positive. A significant association was found between M. paratuberculosis and Crohn's disease (p = 0.02) that was not related to age, gender, place of birth, smoking or alcohol intake. No significant association was detected between M. paratuberculosis and UC or aphthous ulcers; however, one M. paratuberculosis isolate was successfully cultured from a patient with UC. We report the resistance of this isolate to ethambutol, rifampin, clofazamine and streptomycin. Interestingly this isolate could not only survive but could grow slowly at 5 degrees C. We demonstrate a significant association between M. paratuberculosis and CD using multiple pre-validated PCR assays and that M. paratuberculosis can be isolated from patients with UC. PMID- 26849124 TI - Congenic Strains Confirm the Pleiotropic Effect of Chromosome 4 QTL on Mouse Femoral Geometry and Biomechanical Performance. AB - A pleiotropic quantitative trait locus (QTL) for bone geometry and mechanical performance in mice was mapped to distal chromosome 4 via an intercross of recombinant congenic mice HcB-8 and HcB-23. To study the QTL in isolation, we have generated C3H.B10-(rs6355453-rs13478087) (C.B.4.3) and C3H.B10-(rs6369860 D4Mit170) (C.B.4.2) congenic strains that harbor ~20 Mb and ~3 Mb, respectively, of chromosome 4 overlapping segments from C57BL/10ScSnA (B10) within the locus on a C3H/DiSnA (C3H) background. Using 3-point bend testing and standard beam equations, we phenotyped these mice for femoral mid-diaphyseal geometry and biomechanical performance. We analyzed the results via 2-way ANOVA, using sex and genotype as factors. In the C.B.4.3 strain, we found that homozygous B10/B10 male mice had smaller cross sectional area (CSA) and reduced total displacement than homozygous C3H/C3H mice. Sex by genotype interaction was also observed for maximum load and stiffness for C3H/C3H and B10/B10 mice, respectively. In C.B.4.2 strain, we found that homozygous B10/B10 mice had lower total displacement, post yield displacement (PYD), stiffness, yield load and maximum load than mice harboring C3H allele. Sex by genotype interaction was observed in B10/B10 mice for perimeter, outer minor axis (OMA) and CSA. There were no significant differences in tissue level mechanical performance, which suggest that the QTL acts primarily on circumferential bone size. These data confirm the prior QTL mapping data and support other work demonstrating the importance of chromosome 4 QTL on bone modeling and bone responses to mechanical loading. PMID- 26849126 TI - Experiences of a Community-Based Lymphedema Management Program for Lymphatic Filariasis in Odisha State, India: An Analysis of Focus Group Discussions with Patients, Families, Community Members and Program Volunteers. AB - BACKGROUND: Globally 68 million people are infected with lymphatic filariasis (LF), 17 million of whom have lymphedema. This study explores the effects of a lymphedema management program in Odisha State, India on morbidity and psychosocial effects associated with lymphedema. METHODOLOGY/PRINCIPAL FINDINGS: Focus groups were held with patients (eight groups, separated by gender), their family members (eight groups), community members (four groups) and program volunteers (four groups) who had participated in a lymphedema management program for the past three years. Significant social, physical, and economic difficulties were described by patients and family members, including marriageability, social stigma, and lost workdays. However, the positive impact of the lymphedema management program was also emphasized, and many family and community members indicated that community members were accepting of patients and had some improved understanding of the etiology of the disease. Program volunteers and community members stressed the role that the program had played in educating people, though interestingly, local explanations and treatments appear to coexist with knowledge of biomedical treatments and the mosquito vector. CONCLUSIONS/SIGNIFICANCE: Local and biomedical understandings of disease can co-exist and do not preclude individuals from participating in biomedical interventions, specifically lymphedema management for those with lymphatic filariasis. There is a continued need for gender-specific psychosocial support groups to address issues particular to men and women as well as a continued need for improved economic opportunities for LF-affected patients. There is an urgent need to scale up LF-related morbidity management programs to reduce the suffering of people affected by LF. PMID- 26849128 TI - Costs of Rearing the Wrong Sex: Cross-Fostering to Manipulate Offspring Sex in Tammar Wallabies. AB - Sex allocation theory assumes that offspring sex (son vs. daughter) has consequences for maternal fitness. The most compelling experiment to test this theory would involve manipulating offspring sex and measuring the fitness consequences of having the "wrong" sex. Unfortunately, the logistical challenges of such an experiment limit its application. In tammar wallabies (Macropus eugenii), previous evidence suggests that mothers in good body condition are more likely to produce sons compared to mothers in poor condition, in support of the Trivers-Willard Hypothesis (TW) of condition-dependent sex allocation. More recently, we have found in our population of tammar wallabies that females with seemingly poor access to resources (based on condition loss over the dry summer) are more likely to produce sons, consistent with predictions from the Local Resource Competition (LRC) hypothesis, which proposes that production of sons or daughters is driven by the level of potential competition between mothers and philopatric daughters. We conducted a cross-fostering experiment in free-ranging tammar wallabies to disassociate the effects of rearing and birthing offspring of each sex. This allowed us to test the prediction of the LRC hypothesis that rearing daughters reduces the future direct fitness of mothers post-weaning and the prediction of the TW hypothesis that rearing sons requires more energy during lactation. Overall, we found limited costs to the mother of rearing the "wrong" sex, with switching of offspring sex only reducing the likelihood of a mother having a pouch young the following year. Thus, we found some support for both hypotheses in that rearing an unexpected son or an unexpected daughter both lead to reduced future maternal fitness. The study suggests that there may be context specific costs associated with rearing the "wrong" sex. PMID- 26849127 TI - Selective Degradation of Host RNA Polymerase II Transcripts by Influenza A Virus PA-X Host Shutoff Protein. AB - Influenza A viruses (IAVs) inhibit host gene expression by a process known as host shutoff. Host shutoff limits host innate immune responses and may also redirect the translation apparatus to the production of viral proteins. Multiple IAV proteins regulate host shutoff, including PA-X, a ribonuclease that remains incompletely characterized. We report that PA-X selectively targets host RNA polymerase II (Pol II) transcribed mRNAs, while sparing products of Pol I and Pol III. Interestingly, we show that PA-X can also target Pol II-transcribed RNAs in the nucleus, including non-coding RNAs that are not destined to be translated, and reporter transcripts with RNA hairpin structures that block ribosome loading. Transcript degradation likely occurs in the nucleus, as PA-X is enriched in the nucleus and its nuclear localization correlates with reduction in target RNA levels. Complete degradation of host mRNAs following PA-X-mediated endonucleolytic cleavage is dependent on the host 5'->3'-exonuclease Xrn1. IAV mRNAs are structurally similar to host mRNAs, but are synthesized and modified at the 3' end by the action of the viral RNA-dependent RNA polymerase complex. Infection of cells with wild-type IAV or a recombinant PA-X-deficient virus revealed that IAV mRNAs resist PA-X-mediated degradation during infection. At the same time, loss of PA-X resulted in changes in the synthesis of select viral mRNAs and a decrease in viral protein accumulation. Collectively, these results significantly advance our understanding of IAV host shutoff, and suggest that the PA-X causes selective degradation of host mRNAs by discriminating some aspect of Pol II-dependent RNA biogenesis in the nucleus. PMID- 26849129 TI - Xenobiotic Compounds Degradation by Heterologous Expression of a Trametes sanguineus Laccase in Trichoderma atroviride. AB - Fungal laccases are enzymes that have been studied because of their ability to decolorize and detoxify effluents; they are also used in paper bleaching, synthesis of polymers, bioremediation, etc. In this work we were able to express a laccase from Trametes (Pycnoporus) sanguineus in the filamentous fungus Trichoderma atroviride. For this purpose, a transformation vector was designed to integrate the gene of interest in an intergenic locus near the blu17 terminator region. Although monosporic selection was still necessary, stable integration at the desired locus was achieved. The native signal peptide from T. sanguineus laccase was successful to secrete the recombinant protein into the culture medium. The purified, heterologously expressed laccase maintained similar properties to those observed in the native enzyme (Km and kcat and kcat/km values for ABTS, thermostability, substrate range, pH optimum, etc). To determine the bioremediation potential of this modified strain, the laccase-overexpressing Trichoderma strain was used to remove xenobiotic compounds. Phenolic compounds present in industrial wastewater and bisphenol A (an endocrine disruptor) from the culture medium were more efficiently removed by this modified strain than with the wild type. In addition, the heterologously expressed laccase was able to decolorize different dyes as well as remove benzo[alpha]pyrene and phenanthrene in vitro, showing its potential for xenobiotic compound degradation. PMID- 26849130 TI - Quantification of Influenza Virus RNA in Aerosols in Patient Rooms. AB - BACKGROUND: The potential for human influenza viruses to spread through fine particle aerosols remains controversial. The objective of our study was to determine whether influenza viruses could be detected in fine particles in hospital rooms. METHODS AND FINDINGS: We sampled the air in 2-bed patient isolation rooms for four hours, placing cyclone samplers at heights of 1.5m and 1.0m. We collected ten air samples each in the presence of at least one patient with confirmed influenza A virus infection, and tested the samples by reverse transcription polymerase chain reaction. We recovered influenza A virus RNA from 5/10 collections (50%); 4/5 were from particles>4 MUm, 1/5 from 1-4 MUm, and none in particles<1 MUm. CONCLUSIONS: Detection of influenza virus RNA in aerosols at low concentrations in patient rooms suggests that healthcare workers and visitors might have frequent exposure to airborne influenza virus in proximity to infected patients. A limitation of our study was the small sample size. Further studies should be done to quantify the concentration of viable influenza virus in healthcare settings, and factors affecting the detection of influenza viruses in fine particles in the air. PMID- 26849131 TI - Diacerein: Benefits, Risks and Place in the Management of Osteoarthritis. An Opinion-Based Report from the ESCEO. AB - Diacerein is a symptomatic slow-acting drug in osteoarthritis (SYSADOA) with anti inflammatory, anti-catabolic and pro-anabolic properties on cartilage and synovial membrane. It has also recently been shown to have protective effects against subchondral bone remodelling. Following the end of the revision procedure by the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) constituted a panel of 11 experts to better define the real place of diacerein in the armamentarium for treating OA. Based on a literature review of clinical trials and meta-analyses, the ESCEO confirms that the efficacy of diacerein is similar to that of non-steroidal anti-inflammatory drugs (NSAIDs) after the first month of treatment, and superior to that of paracetamol. Additionally, diacerein has shown a prolonged effect on symptoms of several months once treatment was stopped. The use of diacerein is associated with common gastrointestinal disorders such as soft stools and diarrhoea, common mild skin reactions, and, uncommonly, hepatobiliary disorders. However, NSAIDs and paracetamol are known to cause potentially severe hepatic, gastrointestinal, renal, cutaneous and cardiovascular reactions. Therefore, the ESCEO concludes that the benefit-risk balance of diacerein remains positive in the symptomatic treatment of hip and knee osteoarthritis. Furthermore, similarly to other SYSADOAs, the ESCEO positions diacerein as a first-line pharmacological background treatment of osteoarthritis, particularly for patients in whom NSAIDs or paracetamol are contraindicated. PMID- 26849133 TI - Genome Survey Sequencing for the Characterization of the Genetic Background of Rosa roxburghii Tratt and Leaf Ascorbate Metabolism Genes. AB - Rosa roxburghii Tratt is an important commercial horticultural crop in China that is recognized for its nutritional and medicinal values. In spite of the economic significance, genomic information on this rose species is currently unavailable. In the present research, a genome survey of R. roxburghii was carried out using next-generation sequencing (NGS) technologies. Total 30.29 Gb sequence data was obtained by HiSeq 2500 sequencing and an estimated genome size of R. roxburghii was 480.97 Mb, in which the guanine plus cytosine (GC) content was calculated to be 38.63%. All of these reads were technically assembled and a total of 627,554 contigs with a N50 length of 1.484 kb and furthermore 335,902 scaffolds with a total length of 409.36 Mb were obtained. Transposable elements (TE) sequence of 90.84 Mb which comprised 29.20% of the genome, and 167,859 simple sequence repeats (SSRs) were identified from the scaffolds. Among these, the mono (66.30%), di-(25.67%), and tri-(6.64%) nucleotide repeats contributed to nearly 99% of the SSRs, and sequence motifs AG/CT (28.81%) and GAA/TTC (14.76%) were the most abundant among the dinucleotide and trinucleotide repeat motifs, respectively. Genome analysis predicted a total of 22,721 genes which have an average length of 2311.52 bp, an average exon length of 228.15 bp, and average intron length of 401.18 bp. Eleven genes putatively involved in ascorbate metabolism were identified and its expression in R. roxburghii leaves was validated by quantitative real-time PCR (qRT-PCR). This is the first report of genome-wide characterization of this rose species. PMID- 26849132 TI - Drug Treatment of STEMI in the Elderly: Focus on Fibrinolytic Therapy and Insights from the STREAM Trial. AB - Elderly patients constitute a large and growing proportion of ST-elevation myocardial infarction (STEMI) patients, yet they have been under-represented or even excluded from reperfusion trials. Despite evidence that fibrinolysis improves outcomes irrespective of age, many elderly STEMI patients still remain undertreated or subject to major delays to primary percutaneous coronary intervention (PCI). The fear of an excessive risk of intracranial hemorrhage (ICH) in these patients can lead to avoidance of potentially life-saving reperfusion treatment, despite the fact that current STEMI guidelines do not exclude the elderly from a pharmaco-invasive strategy. Age-specific dose reductions have been succesfully made to antithrombotic drugs such as clopidogrel and enoxaparin as an adjunct to fibrinolysis, but until recently no dose adjustments for elderly patients have been applied to the fibrinolytic agents. In the pharmaco-invasive STREAM trial, halving the bolus of tenecteplase for patients aged >75 years because of an unacceptably high ICH rate in the elderly was associated with a more favorable safety/efficacy profile. Whether a pharmaco invasive strategy including half-dose tenecteplase, age- and weight-adjusted enoxaparin, and a tailored P2Y12 inhibitor followed by routine angiography represents a safe and efficacious alternative reperfusion therapy for elderly patients remains to be prospectively assessed in a clinical trial in this age group. PMID- 26849134 TI - Diversity and Stability of Lactic Acid Bacteria in Rye Sourdoughs of Four Bakeries with Different Propagation Parameters. AB - We identified the lactic acid bacteria within rye sourdoughs and starters from four bakeries with different propagation parameters and tracked their dynamics for between 5-28 months after renewal. Evaluation of bacterial communities was performed using plating, denaturing gradient gel electrophoresis, and pyrosequencing of 16S rRNA gene amplicons. Lactobacillus amylovorus and Lactobacillus frumenti or Lactobacillus helveticus, Lactobacillus pontis and Lactobacillus panis prevailed in sourdoughs propagated at higher temperature, while ambient temperature combined with a short fermentation cycle selected for Lactobacillus sanfranciscensis, Lactobacillus pontis, and Lactobacillus zymae or Lactobacillus helveticus, Lactobacillus pontis and Lactobacillus zymae. The ratio of species in bakeries employing room-temperature propagation displayed a seasonal dependence. Introduction of different and controlled propagation parameters at one bakery (higher fermentation temperature, reduced inoculum size, and extended fermentation time) resulted in stabilization of the microbial community with an increased proportion of L. helveticus and L. pontis. Despite these new propagation parameters no new species were detected. PMID- 26849135 TI - Differences in the Comparative Stability of Ebola Virus Makona-C05 and Yambuku Mayinga in Blood. AB - In support of the response to the 2013-2016 Ebola virus disease (EVD) outbreak in Western Africa, we investigated the persistence of Ebola virus/H.sapiens tc/GIN/2014/Makona-C05 (EBOV/Mak-C05) on non-porous surfaces that are representative of hospitals, airplanes, and personal protective equipment. We performed persistence studies in three clinically-relevant human fluid matrices (blood, simulated vomit, and feces), and at environments representative of in flight airline passenger cabins, environmentally-controlled hospital rooms, and open-air Ebola treatment centers in Western Africa. We also compared the surface stability of EBOV/Mak-C05 to that of the prototype Ebola virus/H.sapiens tc/COD/1976/Yambuku-Mayinga (EBOV/Yam-May), in a subset of these conditions. We show that on inert, non-porous surfaces, EBOV decay rates are matrix- and environment-dependent. Among the clinically-relevant matrices tested, EBOV persisted longest in dried human blood, had limited viability in dried simulated vomit, and did not persist in feces. EBOV/Mak-C05 and EBOV/Yam-May decay rates in dried matrices were not significantly different. However, during the drying process in human blood, EBOV/Yam-May showed significantly greater loss in viability than EBOV/Mak-C05 under environmental conditions relevant to the outbreak region, and to a lesser extent in conditions relevant to an environmentally-controlled hospital room. This factor may contribute to increased communicability of EBOV/Mak-C05 when surfaces contaminated with dried human blood are the vector and may partially explain the magnitude of the most recent outbreak, compared to prior outbreaks. These EBOV persistence data will improve public health efforts by informing risk assessments, structure remediation decisions, and response procedures for future EVD outbreaks. PMID- 26849137 TI - Robot-Assisted End-Effector-Based Stair Climbing for Cardiopulmonary Exercise Testing: Feasibility, Reliability, and Repeatability. AB - BACKGROUND: Neurological impairments can limit the implementation of conventional cardiopulmonary exercise testing (CPET) and cardiovascular training strategies. A promising approach to provoke cardiovascular stress while facilitating task specific exercise in people with disabilities is feedback-controlled robot assisted end-effector-based stair climbing (RASC). The aim of this study was to evaluate the feasibility, reliability, and repeatability of augmented RASC-based CPET in able-bodied subjects, with a view towards future research and applications in neurologically impaired populations. METHODS: Twenty able-bodied subjects performed a familiarisation session and 2 consecutive incremental CPETs using augmented RASC. Outcome measures focussed on standard cardiopulmonary performance parameters and on accuracy of work rate tracking (RMSEP-root mean square error). Criteria for feasibility were cardiopulmonary responsiveness and technical implementation. Relative and absolute test-retest reliability were assessed by intraclass correlation coefficients (ICC), standard error of the measurement (SEM), and minimal detectable change (MDC). Mean differences, limits of agreement, and coefficients of variation (CoV) were estimated to assess repeatability. RESULTS: All criteria for feasibility were achieved. Mean V'O2peak was 106+/-9% of predicted V'O2max and mean HRpeak was 99+/-3% of predicted HRmax. 95% of the subjects achieved at least 1 criterion for V'O2max, and the detection of the sub-maximal ventilatory thresholds was successful (ventilatory anaerobic threshold 100%, respiratory compensation point 90% of the subjects). Excellent reliability was found for peak cardiopulmonary outcome measures (ICC >= 0.890, SEM <= 0.60%, MDC <= 1.67%). Repeatability for the primary outcomes was good (CoV <= 0.12). CONCLUSIONS: RASC-based CPET with feedback-guided exercise intensity demonstrated comparable or higher peak cardiopulmonary performance variables relative to predicted values, achieved the criteria for V'O2max, and allowed determination of sub-maximal ventilatory thresholds. The reliability and repeatability were found to be high. There is potential for augmented RASC to be used for exercise testing and prescription in populations with neurological impairments who would benefit from repetitive task-specific training. PMID- 26849136 TI - By Regulating Mitochondrial Ca2+-Uptake UCP2 Modulates Intracellular Ca2+. AB - INTRODUCTION: The possible role of UCP2 in modulating mitochondrial Ca2+-uptake (mCa2+-uptake) via the mitochondrial calcium uniporter (MCU) is highly controversial. METHODS: Thus, we analyzed mCa2+-uptake in isolated cardiac mitochondria, MCU single-channel activity in cardiac mitoplasts, dual Ca2+ transients from mitochondrial ((Ca2+)m) and intracellular compartment ((Ca2+)c) in the whole-cell configuration in cardiomyocytes of wild-type (WT) and UCP2-/- mice. RESULTS: Isolated mitochondria showed a Ru360 sensitive mCa2+-uptake, which was significantly decreased in UCP2-/- (229.4+/-30.8 FU vs. 146.3+/-23.4 FU, P<0.05). Single-channel registrations confirmed a Ru360 sensitive voltage-gated Ca2+-channel in mitoplasts, i.e. mCa1, showing a reduced single-channel activity in UCP2-/- (Po,total: 0.34+/-0.05% vs. 0.07+/-0.01%, P<0.05). In UCP2-/- cardiomyocytes (Ca2+)m was decreased (0.050+/-0.009 FU vs. 0.021+/-0.005 FU, P<0.05) while (Ca2+)c was unchanged (0.032+/-0.002 FU vs. 0.028+/-0.004 FU, P>0.05) and transsarcolemmal Ca2+-influx was inhibited suggesting a possible compensatory mechanism. Additionally, we observed an inhibitory effect of ATP on mCa2+-uptake in WT mitoplasts and (Ca2+)m of cardiomyocytes leading to an increase of (Ca2+)c while no ATP dependent effect was observed in UCP2-/-. CONCLUSION: Our results indicate regulatory effects of UCP2 on mCa2+-uptake. Furthermore, we propose, that previously described inhibitory effects on MCU by ATP may be mediated via UCP2 resulting in changes of excitation contraction coupling. PMID- 26849138 TI - Neutrophil Extracellular Traps Induce Organ Damage during Experimental and Clinical Sepsis. AB - Organ dysfunction is a major concern in sepsis pathophysiology and contributes to its high mortality rate. Neutrophil extracellular traps (NETs) have been implicated in endothelial damage and take part in the pathogenesis of organ dysfunction in several conditions. NETs also have an important role in counteracting invading microorganisms during infection. The aim of this study was to evaluate systemic NETs formation, their participation in host bacterial clearance and their contribution to organ dysfunction in sepsis. C57Bl/6 mice were subjected to endotoxic shock or a polymicrobial sepsis model induced by cecal ligation and puncture (CLP). The involvement of cf-DNA/NETs in the physiopathology of sepsis was evaluated through NETs degradation by rhDNase. This treatment was also associated with a broad-spectrum antibiotic treatment (ertapenem) in mice after CLP. CLP or endotoxin administration induced a significant increase in the serum concentrations of NETs. The increase in CLP induced NETs was sustained over a period of 3 to 24 h after surgery in mice and was not inhibited by the antibiotic treatment. Systemic rhDNase treatment reduced serum NETs and increased the bacterial load in non-antibiotic-treated septic mice. rhDNase plus antibiotics attenuated sepsis-induced organ damage and improved the survival rate. The correlation between the presence of NETs in peripheral blood and organ dysfunction was evaluated in 31 septic patients. Higher cf-DNA concentrations were detected in septic patients in comparison with healthy controls, and levels were correlated with sepsis severity and organ dysfunction. In conclusion, cf-DNA/NETs are formed during sepsis and are associated with sepsis severity. In the experimental setting, the degradation of NETs by rhDNase attenuates organ damage only when combined with antibiotics, confirming that NETs take part in sepsis pathogenesis. Altogether, our results suggest that NETs are important for host bacterial control and are relevant actors in the pathogenesis of sepsis. PMID- 26849139 TI - Gene Structures, Evolution and Transcriptional Profiling of the WRKY Gene Family in Castor Bean (Ricinus communis L.). AB - WRKY proteins comprise one of the largest transcription factor families in plants and form key regulators of many plant processes. This study presents the characterization of 58 WRKY genes from the castor bean (Ricinus communis L., Euphorbiaceae) genome. Compared with the automatic genome annotation, one more WRKY-encoding locus was identified and 20 out of the 57 predicted gene models were manually corrected. All RcWRKY genes were shown to contain at least one intron in their coding sequences. According to the structural features of the present WRKY domains, the identified RcWRKY genes were assigned to three previously defined groups (I-III). Although castor bean underwent no recent whole genome duplication event like physic nut (Jatropha curcas L., Euphorbiaceae), comparative genomics analysis indicated that one gene loss, one intron loss and one recent proximal duplication occurred in the RcWRKY gene family. The expression of all 58 RcWRKY genes was supported by ESTs and/or RNA sequencing reads derived from roots, leaves, flowers, seeds and endosperms. Further global expression profiles with RNA sequencing data revealed diverse expression patterns among various tissues. Results obtained from this study not only provide valuable information for future functional analysis and utilization of the castor bean WRKY genes, but also provide a useful reference to investigate the gene family expansion and evolution in Euphorbiaceus plants. PMID- 26849140 TI - Similar result after non-elective and elective surgery for lumbar disc herniation: an observational study based on the SweSpine register. AB - PURPOSE: Surgery for lumbar disc herniation (LDH) is most often elective, but intense pain may require more urgent, non-elective, treatment. It was hypothesized that non-elective treatment could be associated with a less favourable outcome than elective surgery. The aim of this study was to compare 1 2-year outcome after non-elective and elective surgery for treatment of para median LDH using data from the Swedish Spine register (SweSpine). METHODS: Pre- and postoperative data were available for 301 non-elective and 2364 elective cases. Patient reported outcome measures (PROMs) were; Visual Analogue Scale (VAS) leg and back pain, Oswestry Disability Index (ODI), EuroQol five-Dimensions (EQ-5D) and patient satisfaction. Postoperative p values were adjusted for baseline differences. RESULTS: Preoperative mean (SD) in the non-elective and elective groups were for VAS leg pain 81 (22) and 65 (24), for VAS back pain 51 (33) and 45 (28), for ODI 66 (20) and 45 (17) and for EQ-5D 0.024 (0.35) and 0.31 (0.33), respectively, (p for all <0.001). Postoperative VAS leg pain was 23 (28) in the non-elective group and 20 (26) in the elective group (p = 0.19). Corresponding figures were for VAS back pain 25 (27) and 24 (27) (p = 0.69), ODI 19 (17) and 17 (17) (p = 0.052) and for EQ-5D 0.70 (0.28) and 0.73 (0.29) (p = 0.73). Patient satisfaction did not differ between the groups (p = 0.78). CONCLUSIONS: Even if non-elective patients preoperatively had substantially more pain, higher disability and poorer quality of life than elective patients, postoperative differences were clinically small. Patient satisfaction did not differ. PMID- 26849141 TI - A prospective clinical and radiographic 12-month outcome study of patients undergoing single-level anterior cervical discectomy and fusion for symptomatic cervical degenerative disc disease utilizing a novel viable allogeneic, cancellous, bone matrix (trinity evolutionTM) with a comparison to historical controls. AB - PURPOSE: This multicenter clinical study was performed to assess the safety and effectiveness of Trinity Evolution((r)) (TE), a viable cellular bone allograft, in combination with a PEEK interbody spacer and supplemental anterior fixation in patients undergoing anterior cervical discectomy and fusion (ACDF). METHODS: In a prospective, multi-center study, 31 patients that presented with symptomatic cervical degeneration at one vertebral level underwent ACDF with a PEEK interbody spacer (Orthofix, Inc., Lewisville, TX, USA) and supplemental anterior fixation. In addition all patients had the bone graft substitute, Trinity Evolution (Musculoskeletal Transplant Foundation, Edison, NJ, USA), placed within the interbody spacer. At 6 and 12 months, radiographic fusion was evaluated as determined by independent radiographic review of angular motion (<=4 degrees ) from flexion/extension X-rays combined with presence of bridging bone across the adjacent endplates on thin cut CT scans. In addition other metrics were measured including function as assessed by the Neck Disability Index (NDI), and neck and arm pain as assessed by individual Visual Analog Scales (VAS). RESULTS: The fusion rate for patients using a PEEK interbody spacer in combination with TE was 78.6 % at 6 months and 93.5 % at 12 months. When considering high risk factors, 6 month fusion rates for patients that were current or former smokers, diabetic, overweight or obese/extremely obese were 70 % (7/10), 100 % (1/1), 70 % (7/10), and 82 % (9/11), respectively. At 12 months, the fusion rates were 100 % (12/12), 100 % (2/2), 100 % (11/11) and 85 % (11/13), respectively. Neck function, and neck/arm pain were found to significantly improve at both time points. No serious allograft related adverse events occurred and none of the 31 patients had subsequent additional cervical surgeries. CONCLUSIONS: Patients undergoing single level ACDF with TE in combination with a PEEK interbody spacer and supplemental anterior fixation had a high rate of fusion success without serious allograft related adverse events. PMID- 26849142 TI - Postoperative dysesthesia in minimally invasive transforaminal lumbar interbody fusion: a report of five cases. AB - OBJECTIVE: Minimally invasive transforaminal lumbar interbody fusion (misTLIF) can potentially lead to dorsal root ganglion (DRG) injury which may cause postoperative dysesthesia (POD). The purpose of retrospective study was to describe the uncommon complication of POD in misTLIF. METHODS: Between January 2010 and December 2014, 539 patients were treated with misTLIF in investigator group. POD was defined as dysesthetic pain or burning dysesthesia at a proper DRG innervated region, whether spontaneous or evoked. Non-steroidal antiinflammatory drugs, central non-opioid analgesic agent, neuropathic pain drugs and/or intervertebral foramen block were selectively used to treat POD. RESULTS: There were five cases of POD (5/539, 0.9 %), which consisted of one patient in recurrent lumbar disc herniation (1/36, 3 %), one patient in far lateral lumbar disc herniation (1/34, 3 %), and 3 patients in lumbar spondylolisthesis (3/201, 1 %). Two DRG injury cases were confirmed by revision surgery. After the treatment by drugs administration plus DRG block, all patients presented pain relief with duration from 22 to 50 days. A gradual pain moving to distal end of a proper DRG innervated region was found as the beginning of end. CONCLUSIONS: Although POD is a unique and rare complication and maybe misdiagnosed as nerve root injury in misTLIF, combination drug therapy and DRG block have an effective result of pain relief. The appearance of a gradual pain moving to distal end of a proper DRG innervated region during recovery may be used as a sign for the good prognosis. PMID- 26849143 TI - An entrapped in flagranti thrombus. PMID- 26849144 TI - Effects of cigarette smoking on platelet reactivity during P2Y12 inhibition in patients with myocardial infarction undergoing drug-eluting stent implantation: results from the prospective cigarette smoking on platelet reactivity (COPTER) study. AB - Interaction between cigarette smoking and efficacy of oral antiplatelet drugs is not definitely elucidated. We evaluated the effects of cigarette smoking on platelet reactivity in patients receiving different oral P2Y12 antagonists after myocardial infarction (MI) and drug-eluting stent (DES) implantation. Two-hundred five consecutive current smokers receiving DES implantation after ST-segment elevation MI were enrolled. All patients were aspirin-treated and were on chronic therapy with clopidogrel (N = 59), prasugrel (N = 71) or ticagrelor (N = 75); by protocol, all patients at baseline had no high on-treatment platelet reactivity by the VerifyNow P2Y12 assay. Platelet reactivity, expressed by P2Y12 reaction units (PRU), was measured in all patients at baseline (T0), after a 15-day period of smoking cessation (T1) and after further 15 days of smoking resumption (T2). In the overall population there was a modest, albeit significant, reduction of PRU values from T0 to T1 (from 173 +/- 14 to 165 +/- 17, P < 0.0001); resumption of cigarette smoking was associated with re-increase of platelet reactivity (from 165 +/- 17 at T1 to 170 +/- 17 at T2, P = 0.0002). These variations were consistent in the subgroups receiving clopidogrel, prasugrel or ticagrelor and were irrespective of the number of cigarettes smoked. In conclusion, cigarette smoking weakly influences antiplatelet effects of oral P2Y12 inhibition and this was irrespective of the type of antiplatelet agent; thus, interaction between cigarette smoking and efficacy of oral antiplatelet drugs is modest and unlikely translates into clinical effects (ClinicalTrials.gov Identifier: NCT02026713). PMID- 26849146 TI - Increased Risk of Stroke in Patients with Isolated Third, Fourth, or Sixth Cranial Nerve Palsies: A Nationwide Cohort Study. AB - BACKGROUND AND PURPOSE: The aim of this nationwide cohort study was to evaluate whether the occurrence of isolated 3rd, 4th or 6th cranial nerve (CN) palsies is associated with a higher risk of ischemic stroke. METHODS: This study utilized data from Taiwan Longitudinal Health Insurance Database during 1995-2012. Subjects aged 20 years or older who had isolated CN 3/4/6 palsies diagnosed by a neurologist or ophthalmologist between January 2000 and December 2011 were included. A set of propensity score matched, randomly sampled patients who had never been diagnosed with CN 3/4/6 palsies were extracted to constitute the control group (cases and controls = 1:4). All subjects were followed until death, loss due to follow-up or completion of the study. Cox proportional hazard regression model stratified by matched pairs was used to estimate the hazards ratio (HR) of ischemic stroke. RESULTS: A total of 657 patients with isolated CN 3/4/6 palsies (61.1% male, mean age 54.8 years) were identified. Compared with control group, the patients with isolated CN 3/4/6 palsies exhibited an increased risk of ischemic stroke (CN3: adjusted HR 3.69 (95% CI 2.20-6.19); CN4: 2.71 (95% CI 1.11-6.64); CN6: 2.15 (95% CI 1.31-3.52)). The association between CN 3/4/6 palsies and ischemic stroke was detected in both separate subgroup and sensitivity analyses. CONCLUSIONS: The patients with CN 3/4/6 palsies exhibited an increased risk of developing ischemic stroke. Therefore, isolated ocular motor nerves palsies appear to represent an unrecognized risk factor for ischemic stroke, and these require further confirmation and exploration. PMID- 26849147 TI - Complications arising from cardiac implantable electrophysiological devices: review of epidemiology, pathogenesis and prevention for the clinician. AB - Cardiac implantable electronic devices (CIEDs) which include devices such as permanent pacemakers, implantable cardioverter-defibrillators and cardiac resynchronization therapy devices are well established therapies that have been shown to improve quality of life and prolong survival in appropriately selected patients, and are being increasing utilized across the world. However, CIED implantations are invasive procedures and a thorough understanding of the potential complications is required to prevent deleterious patient outcomes. In this review, we will discuss frequent complications (infection, hematoma or bleeding, and procedural mechanical complications) that may harm patients after CIED implantation, and the steps that can be taken to minimize their risk. This is particularly relevant to trainees/ clinicians who either perform these procedures or refer patients for CIED implantation. PMID- 26849145 TI - Impaired expression of DICER and some microRNAs in HBZ expressing cells from acute adult T-cell leukemia patients. AB - Global dysregulation of microRNAs (miRNAs), a class of non-coding RNAs that regulate genes expression, is a common feature of human tumors. Profiling of cellular miRNAs on Adult T cell Leukemia (ATL) cells by Yamagishi et al. showed a strong decrease in expression for 96.7% of cellular miRNAs in ATL cells. However, the mechanisms that regulate the expression of miRNAs in ATL cells are still largely unknown. In this study, we compared the expression of 12 miRs previously described for being overexpress by Tax and the expression of several key components of the miRNAs biogenesis pathways in different HBZ expressing cell lines as well as in primary CD4 (+) cells from acute ATL patients. We showed that the expression of miRNAs and Dicer1 were downregulated in cells lines expressing HBZ as well as in fresh CD4 (+) cells from acute ATL patients. Using qRT-PCR, western blotting analysis and Chromatin Immunoprecipitation, we showed that dicer transcription was regulated by c-Jun and JunD, two AP-1 transcription factors. We also demonstrated that HBZ affects the expression of Dicer by removing JunD from the proximal promoter. Furthermore, we showed that at therapeutic concentration of 1mM, Valproate (VPA) an HDAC inhibitors often used in cancer treatment, rescue Dicer expression and miRNAs maturation. These results might offer a rationale for clinical studies of new combined therapy in an effort to improve the outcome of patients with acute ATL. PMID- 26849148 TI - S3 State of the O2-Evolving Complex of Photosystem II: Insights from QM/MM, EXAFS, and Femtosecond X-ray Diffraction. AB - The oxygen-evolving complex (OEC) of photosystem II has been studied in the S3 state by electron paramagnetic resonance, extended X-ray absorption fine structure (EXAFS), and femtosecond X-ray diffraction (XRD). However, the actual structure of the OEC in the S3 state has yet to be established. Here, we apply hybrid quantum mechanics/molecular mechanics methods and propose a structural model that is consistent with EXAFS and XRD. The model supports binding of water ligands to the cluster in the S2 -> S3 transition through a carousel rearrangement around Mn4, inspired by studies of ammonia binding. PMID- 26849150 TI - 2-Bromo-6-isocyanopyridine as a Universal Convertible Isocyanide for Multicomponent Chemistry. AB - The development of 2-isocyanopyridines as novel convertible isocyanides for multicomponent chemistry is reported. Comparison of 12 representatives of this class revealed 2-bromo-6-isocyanopyridine as the optimal reagent in terms of stability and synthetic efficiency. It combines sufficient nucleophilicity with good leaving group capacity of the resulting amide moiety under both basic and acidic conditions. To demonstrate the practical utility of this reagent, an efficient two-step synthesis of the potent opioid carfentanil is presented. PMID- 26849151 TI - Evaluation of the association of single nucleotide polymorphisms in the PRPH2 gene with adult-onset foveomacular vitelliform dystrophy. AB - OBJECTIVE: A minority of patients with adult-onset foveomacular vitelliform dystrophy (AFVD) carry mutations in the PRPH2 gene. This gene is highly polymorphic and it was suggested that single-nucleotide polymorphisms (SNPs) in PRPH2 may also be associated with AFVD. We aimed to evaluate for such an association. METHODS: A single center cohort from a tertiary referral center including 52 consecutive patients with a clinical diagnosis of AFVD and 91 unaffected individuals was assessed. Sanger sequencing was performed for the PRPH2, BEST1, and IMPG1/2 genes. Investigation as to the frequency of minor alleles for SNPs in PRPH2 was performed and compared to HapMap and Exome Variant Server (EVS) data. RESULTS: None of the patients carry a mutation in PRPH2, BEST1, or IMPG1/2. Five of 14 known SNPs (rs835, rs361524, rs434102, rs425876, rs390659) in exon 3 of PRPH2 were identified in AFVD patients. A high frequency and percentage of minor alleles of these five SNPs was found in the Israeli AFVD patients and controls compared with European, Chinese, Japanese and African populations identified via HapMap and EVS (p < 0.05). Power calculation suggested that the sample size was sufficient (80%) to rule out an association with an odds ratio above 2.5. CONCLUSIONS: These results suggest that genetic variants in PRPH2 do not compose a major genetic risk factor for AFVD. The Israeli population shows a higher percentage of minor allele frequencies in SNPs in the PRPH2 gene, as compared with other populations. This emphasizes the need for appropriate genetic background when performing SNP association testing. PMID- 26849152 TI - Oral Sex, Young People, and Gendered Narratives of Reciprocity. AB - Young people in many countries report gender differences in giving and receiving oral sex, yet examination of young people's own perspectives on gender dynamics in oral heterosex are relatively rare. We explored the constructs and discourses 16- to 18-year-old men and women in England used in their accounts of oral sex during in-depth interviews. Two contrasting constructs were in circulation in the accounts: on one hand, oral sex on men and women was narrated as equivalent, while on the other, oral sex on women was seen as "a bigger deal" than oral sex on men. Young men and women used a "give and take" discourse, which constructed the mutual exchange of oral sex as "fair." Appeals to an ethic of reciprocity in oral sex enabled women to present themselves as demanding equality in their sexual interactions, and men as supporting mutuality. However, we show how these ostensibly positive discourses about equality also worked in narratives to obscure women's constrained agency and work with respect to giving oral sex. PMID- 26849149 TI - Overcoming Resistance to Endocrine Therapy in Breast Cancer: New Approaches to a Nagging Problem. AB - In the majority of women, breast cancer progresses through increased transcriptional activity due to over-expressed oestrogen receptors (ER). Therapeutic strategies include: (i) reduction of circulating ovarian oestrogens or of peripherally produced oestrogen (in postmenopausal women) with aromatase inhibitors and (ii) application of selective ER modulators for receptor blockade. The success of these interventions is limited by the variable but persistent onset of acquired resistance and by an intrinsic refractiveness which manifests despite adequate levels of ER in about 50% of patients with advanced metastatic disease. Loss of functional ER leads to endocrine insensitivity, loss of cellular adhesion and polarity, and increased migratory potential due to trans differentiation of the epithelial cancer cells into a mesenchymal-like phenotype (epithelial-mesenchymal transition; EMT). Multiple mechanisms contributing to therapeutic failure have been proposed: (i) loss or modification of ER expression including epigenetic mechanisms, (ii) agonistic actions of selective ER modulators that may be enhanced through an increased expression of co-activators, (iii) attenuation of the tamoxifen metabolism through expression of genetic variants of P450 cytochromes which leads to more or less active metabolites and (iv) increased growth factor signalling particularly through epidermal growth factor receptor activation of pathways involving keratinocyte growth factor, platelet-derived growth factor, and nuclear factor x03BA;B. In addition, the small non-coding microRNAs, recently recognized as critical gene regulators, exhibit differential expression in tamoxifen-sensitive versus resistant cell lines. Several studies suggest the potential of using these either as targets or as therapeutic agents to modulate EMT regulators as a means of reversing the aggressive metastatic phenotype by reversal of the EMT, with the added benefit of re-sensitization to anti-oestrogens. PMID- 26849153 TI - Post-Radiation Therapy Imaging Appearances in Cervical Carcinoma. AB - Locally advanced and node-positive cervical cancers are usually treated with external beam radiation therapy and intracavitary brachytherapy with concomitant chemotherapy. In patients with locally advanced cervical cancer, imaging plays a vital role in pretreatment planning, assessment of primary tumor response to treatment, follow-up, and evaluation of treatment-related complications. Radiation therapy planning is crucial to successful local and regional control of disease. Patient selection criteria for radiation therapy with concomitant chemotherapy are described, as is assessment of treatment response of the primary cervical tumor at magnetic resonance (MR) imaging. Image interpretation can be challenging because of radiation therapy-related changes in the pelvic organs. Expected changes in the bladder, bowel, and bone marrow after radiation therapy are described, and multimodality imaging findings at computed tomography, MR imaging, and fluorine 18 fluorodeoxyglucose positron emission tomography are illustrated. Complications after radiation therapy have declined over recent years because of targeted radiation therapy. These complications can be divided into acute and chronic effects, where acute toxic effects occur within weeks of treatment. Chronic complications include cervical stenosis, small bowel stricture, fistula formation, and insufficiency fractures. Imaging is an essential tool in the care of patients with cervical cancer treated with chemotherapy and radiation therapy. The reporting radiologist should be familiar with the expected imaging appearances of the pelvic organs after radiation therapy, as well as potential complications, to avoid pitfalls in image interpretation. PMID- 26849154 TI - Chemical Shift MR Imaging of the Adrenal Gland: Principles, Pitfalls, and Applications. AB - Adrenal lesions are a common imaging finding. The vast majority of adrenal lesions are adenomas, which contain intracytoplasmic (microscopic) fat. It is important to distinguish between adenomas and malignant tumors, and chemical shift magnetic resonance (MR) imaging can be used to accomplish this distinction by depicting the fat in adenomas. Chemical shift imaging is based on the difference in precession frequencies of water and fat molecules, which causes them to be in different relative phases during the acquisition sequence and allows in-phase and opposed-phase images to be obtained. It is important to acquire these images by using the earliest possible echo times, with the opposed phase echo before the in-phase echo, and by using a single breath hold to preserve diagnostic accuracy. Intracytoplasmic fat is depicted as signal drop on opposed-phase images when compared with in-phase images. Both qualitative and quantitative methods for assessing signal drop are detailed. The appearances of adrenal adenomas and other adrenal tumors on chemical shift MR images are described, and discriminatory ability at chemical shift MR imaging compared with that at adrenal computed tomography (CT) is explained. Other adrenal-related conditions in which chemical shift MR imaging is helpful are also discussed. Chemical shift MR imaging is a robust tool for evaluating adrenal lesions that are indeterminate at nonenhanced CT. However, it is important to know the advantages and disadvantages, including several potential imaging pitfalls. The characterization of adrenal lesions by using chemical shift MR imaging and adrenal CT should always occur in the appropriate clinical setting. PMID- 26849155 TI - Therapeutic Antibody Engineering To Improve Viscosity and Phase Separation Guided by Crystal Structure. AB - Antibodies at high concentrations often reveal unanticipated biophysical properties suboptimal for therapeutic development. The purpose of this work was to explore the use of point mutations based on crystal structure information to improve antibody physical properties such as viscosity and phase separation (LLPS) at high concentrations. An IgG4 monoclonal antibody (Mab4) that exhibited high viscosity and phase separation at high concentration was used as a model system. Guided by the crystal structure, four CDR point mutants were made to evaluate the role of hydrophobic and charge interactions on solution behavior. Surprisingly and unpredictably, two of the charge mutants, R33G and N35E, showed a reduction in viscosity and a lower propensity to form LLPS at high concentration compared to the wild-type (WT), while a third charge mutant S28K showed an increased propensity to form LLPS compared to the WT. A fourth mutant, F102H, had reduced hydrophobicity, but unchanged viscosity and phase separation behavior. We further evaluated the correlation of various biophysical measurements including second virial coefficient (A2), interaction parameter (kD), weight-average molecular weight (WAMW), and hydrodynamic diameters (DH), at relatively low protein concentration (4 to 15 mg/mL) to physical properties, such as viscosity and liquid-liquid phase separation (LLPS), at high concentration. Surprisingly, kD measured using dynamic light scattering (DLS) at low antibody concentration correlated better with viscosity and phase separation than did A2 for Mab4. Our results suggest that the high viscosity and phase separation observed at high concentration for Mab4 are mainly driven by charge and not hydrophobicity. PMID- 26849157 TI - Decentralizing Access to Antiretroviral Therapy for Children Living with HIV in Swaziland. AB - BACKGROUND: In 2007, Swaziland initiated a hub-and-spoke model for decentralizing antiretroviral therapy (ART) access for HIV-infected children (<15 years old). Decentralization was facilitated through (1) down referral of stable children on ART from overburdened central facilities (hubs) to primary healthcare clinics (spokes) and (2) pediatric ART initiation at spokes (spoke initiation). METHODS: We conducted a nationally representative retrospective cohort study among children starting ART during 2004-2010 to assess effect of down referral and spoke initiation on rates of loss to follow-up (LTFU), death and attrition (death or LTFU). Twelve of 28 pediatric ART hubs were randomly selected using probability-proportional-to-size sampling. Seven selected facilities had initiated hub-and-spoke decentralization by study start; at these facilities, 901 of 1893 hub-initiated and maintained (hub-maintained) children and 495 of 1105 down-referred or spoke-initiated children were randomly selected for record abstraction. At the 5 hub-only facilities, 612 of 1987 children were randomly selected. Multivariable proportional hazards regression was used to estimate adjusted hazard ratios (AHR) for effect of down referral (a time-varying covariate) and spoke initiation on outcomes. RESULTS: Among 2008 children at ART initiation, median age was 5.0 years, median CD4% 12.0%, median CD4 count 358 cells/uL and median weight-for-age Z score -1.91. Controlling for known confounders, down referral was strongly protective against LTFU (AHR: 0.40; 95% confidence interval: 0.20-0.79) and attrition (AHR: 0.46; 95% confidence interval: 0.26-0.83) but not mortality. Compared with hub-only children or hub maintained children, spoke-initiated children had similar outcomes. CONCLUSIONS: Decentralization of pediatric ART through down referral and spoke initiation within a hub-and-spoke system should be continued and might improve program outcomes. PMID- 26849158 TI - Clinical Experience with Daptomycin for the Treatment of Gram-positive Infections in Children and Adolescents. AB - BACKGROUND: This subgroup analysis of the European Cubicin Outcomes Registry Experience evaluated the safety and effectiveness of daptomycin in children and adolescent patients (<18 years). METHODS: Clinical outcomes at the end of therapy were assessed as success (cured or improved), failure or nonevaluable. Safety was assessed for up to 30 days post treatment. RESULTS: Eighty-one children and adolescent patients were included in this study. The most common primary infections were bacteremia (19.8%), complicated skin and soft-tissue infection (18.5%), osteomyelitis (13.6%), endocarditis (12.3%), foreign body/prosthetic infection (12.3%), uncomplicated skin and soft-tissue infection (9.9%) and other (13.6%). Daptomycin doses ranged from 4 to >10 mg/kg/day. Median duration of therapy was 12.5 (interquartile range, 7-25; mean, 16.7; standard deviation, 12.8) days. Staphylococcus aureus (46.7%) was the most commonly isolated pathogen (23.8% methicillin-resistant S. aureus). Forty-nine (60.5%) patients completed daptomycin therapy without further antibiotics, 27 (33.3%) switched to another antibiotic, 4 (4.9%) discontinued because of adverse events (AEs) and 1 (1.2%) discontinued because of other reason. Overall, 75 (92.6%; 95% confidence interval: 95.2-100.0%) patients achieved clinical success; 39 of 41 (95.1%) patients receiving daptomycin monotherapy and 36 of 40 (90.0%) patients receiving concomitant antibiotics. Six (7.4%) patients reported AEs, including 1 patient with increased blood creatine phosphokinase. Three (3.7%) patients had serious AEs; 1 (1.2%) had a serious AE possibly related to daptomycin. CONCLUSION: Daptomycin, alone or combined with other antibiotics and/or surgery, demonstrated high clinical success rates against a wide variety of infections and was well tolerated in children and adolescents. PMID- 26849159 TI - Up-Regulation of Pro-Inflammatory Cytokines and Chemokine Production in Avian Influenza H9N2 Virus-Infected Human Lung Epithelial Cell Line (A549). AB - Influenza H9N2 virus mostly infects avian species but poses a potential health risk to humans. Little is known about the mammalian host immune responses to H9N2 virus. To obtain insight into the innate immune responses of human lung epithelial cells to the avian H9N2 virus, the expressions of pro-inflammatory cytokines and chemokine in the human airway epithelial cells infected with avian H9N2 virus were examined by real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). H9N2 virus was able to cultivate in the human lung epithelial cell line (A549) and stimulate production of pro-inflammatory cytokines (IL-1beta, IL-6) and chemokine (IL-8). Expressions of cytokine genes were up-regulated to a significantly higher level for IL-1beta (p < 0.01), IL-6 (p < 0.01 after 12 hours and p < 0.05 after 24 hours) and IL-8 (p < 0.01 after 12 hours and p < 0.001 after 24 hours) in virus-cultured A549 cells as compared with non-virus-cultured cells. The amount of IL-6 and IL-1beta proteins secreted into the culture medium was also increased after virus culture infection of A549 cell line compared to non-virus-cultured A549 cells and were significant in both IL-1beta (p < 0.05 in 18 hours and p < 0.001 in 24-48 hours harvested supernatant) and IL-6 (p < 0.001). Silencing the p65 component of NF-kappaB in A549 cells suppressed the stimulatory effects of influenza virus on secretion of pro-inflammatory cytokines and chemokine. The findings in this study will broaden our understanding of host innate immune mechanisms and the pathogenesis of H9N2 influenza viruses in human respiratory epithelium. PMID- 26849160 TI - Chasing the Elusive Benzofuran Impurity of the THR Antagonist NH-3: Synthesis, Isotope Labeling, and Biological Activity. AB - We have synthesized and established the structure of a long-suspected, but hitherto unknown, benzofuran side product (EBI) formed during the synthesis of NH 3. Understanding the mechanism of its formation has enabled isotope (D) labeling. We further developed a highly efficient method for separating EBI from NH-3. Interestingly, EBI was found to be a very potent thyroid hormone receptor (THR) agonist, while NH-3 is an antagonist. In this process, we have also achieved a significantly improved synthesis of NH-3. PMID- 26849161 TI - Effects of multiwalled carbon nanotubes on electrospun poly(lactide-co-glycolide) based nanocomposite scaffolds on neural cells proliferation. AB - The repair of nerves remains a major challenge in neuron-regeneration. In this study, poly(lactic-co-glycolic acid)/multi-walled carbon nanotubes (PLGA/MWCNTs) nanofibrous scaffolds were fabricated by electrospinning method. The surface morphology, physical, and mechanical properties were characterized through scanning electron microscopy (SEM), transmission electron microscopy, and tensile tests, respectively. SEM analysis, Live/Dead staining, immunostaining assays were performed to evaluate neural cells growth. Blending PLGA with MWCNTs resulted in increase diameter and porosity of the scaffolds, and exhibited better mechanical properties. The results demonstrated that the scaffolds with higher MWCNTs concentration provided better survival for neural cells after 8 days of culture, especially for astrocytes growth. This could be useful in treating the disease like multiple sclerosis that causing central nervous system demyelination and axonal injury. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 934-943, 2017. PMID- 26849156 TI - Specification and function of hemogenic endothelium during embryogenesis. AB - Hemogenic endothelium is a specialized subset of developing vascular endothelium that acquires hematopoietic potential and can give rise to multilineage hematopoietic stem and progenitor cells during a narrow developmental window in tissues such as the extraembryonic yolk sac and embryonic aorta-gonad mesonephros. Herein, we review current knowledge about the historical and developmental origins of hemogenic endothelium, the molecular events that govern hemogenic specification of vascular endothelial cells, the generation of multilineage hematopoietic stem and progenitor cells from hemogenic endothelium, and the potential for translational applications of knowledge gained from further study of these processes. PMID- 26849162 TI - Pulmonary hypertension and right ventricular failure in broiler chickens reared at high altitude is affected by dietary source of n-6 and n-3 fatty acids. AB - The present study evaluated the development of pulmonary hypertension and right ventricular failure in broiler chickens reared at high altitude (2100 m) as affected by dietary intake of n-3 and n-6 fatty acid sources. Flax oil and soy oil were used as sources of n-3 and n-6 fatty acids, respectively, either with or without alpha-tocopheryl acetate. A total of 192 day-old broiler chicks (Ross 308) were used in a completely randomized design using isoenergetic and isonitrogenous experimental diets. Results showed that dietary flax oil significantly (p < 0.05) improved feed conversion ratio during 21-42 days of age. However, body weight gain did not significantly differ among the experimental groups in entire trial. Birds received flax oil had significantly higher serum concentration of nitric oxide (NO) but they had lower serum concentration of malondialdehyde when compared with their counterparts fed with soy oil. Liver and abdominal fat weights were significantly (p < 0.05) reduced by substitution of soy oil for flax oil. The right-to-total ventricle weight ratio (RV/TV) and mortality from pulmonary arterial hypertension (PAH) were significantly (p < 0.05) decreased in birds that received flax oil. In conclusion, n-3 fatty acids could significantly reduce RV:TV and PAH mortality in birds by increasing circulatory level of NO and suppressing hepatic lipogenesis. PMID- 26849164 TI - Current laboratory approaches to diagnosis of CNS fungal infections. PMID- 26849165 TI - Detection of generic differential RNA processing events from RNA-seq data. AB - RNA-seq data analysis has revealed abundant alternative splicing in eukaryotic mRNAs. However, splicing is only one of many processing events that transcripts may undergo during their lifetime. We present here RNAprof (RNA profile analysis), a program for the detection of differential processing events from the comparison of RNA-seq experiments. RNAprof implements a specific gene-level normalization procedure and compares RNA-seq coverage profiles at nucleotide resolution to detect regions of significant coverage differences, independently of splice sites or other gene features. We used RNAprof to analyze the effect of alternative-splicing regulators NSRa and NSRb on the Arabidopsis thaliana transcriptome. A number of intron retention events and alternative transcript structures were specifically detected by RNAprof and confirmed by qRT-PCR. Further tests using a public Mus musculus RNA-seq dataset and comparisons with other RNA isoform predictors showed that RNAprof uniquely identified sets of highly significant processing events as well as other relevant library-specific differences in RNA-seq profiles. This highlights an important layer of variation that remains undetected by current protocols for RNA-seq analysis. PMID- 26849166 TI - Asthma management programs for primary care providers: increasing adherence to asthma guidelines. AB - PURPOSE OF REVIEW: This article reviews new approaches, facilitators, barriers, and opportunities to increasing guideline-adherent care for children with asthma by primary care clinicians. RECENT FINDINGS: Primary care clinicians are challenged by the volume of guidelines and want transparent guidelines that are easy to use and that can be used in complex patients with multiple comorbidities. Programs that use decision support tools and electronic technologies and provide support from individuals new to the medical home such as panel management assistants, community health workers, patient advocates, practice facilitators, school nurses, and pharmacists may enhance use of guidelines by primary care clinicians and reduce asthma morbidity. Primary care clinician burnout and difficulty incorporating electronic asthma decision tools into current workflow are recently recognized barriers to guideline integration and improved asthma outcomes. In addition, many of these interventions are labor intensive, costly and may not be capable of being widely disseminated. SUMMARY: Programs that simplify guidelines, provide decision support tools and use electronic technologies and an expanded medical team may improve the quality of asthma care provided by the primary care community to children and their families with asthma. PMID- 26849167 TI - Novel Multifunctional Nanomatrix Reduces Inflammation in Dynamic Conditions in Vitro and Dilates Arteries ex Vivo. AB - Inflammatory responses play a critical role in tissue-implant interactions, often limiting current implant utility. This is particularly true for cardiovascular devices. Existing stent technology does little to avoid or mitigate inflammation or to influence the vasomotion of the artery after implantation. We have developed a novel endothelium-mimicking nanomatrix composed of peptide amphiphiles that enhances endothelialization while decreasing both smooth muscle cell proliferation and platelet adhesion. Here, we evaluated whether the nanomatrix could prevent inflammatory responses under static and physiological flow conditions. We found that the nanomatrix reduced monocyte adhesion to endothelial cells and expression of monocyte inflammatory genes (TNF-alpha, MCP 1, IL-1beta, and IL-6). Furthermore, the nitric-oxide releasing nanomatrix dramatically attenuated TNF-alpha-stimulated inflammatory responses as demonstrated by significantly reduced monocyte adhesion and inflammatory gene expression in both static and physiological flow conditions. These effects were abolished by addition of a nitric oxide scavenger. Finally, the nanomatrix stimulated vasodilation in intact rat mesenteric arterioles after constriction with phenylephrine, demonstrating the bioavailability and bioactivity of the nanomatrix, as well as exhibiting highly desired release kinetics. These results demonstrate the clinical potential of this nanomatrix by both preventing inflammatory responses and promoting vasodilation, critical improvements in stent and cardiovascular device technology. PMID- 26849168 TI - A Multi-Stakeholder Process to Transform a Community-based Screening and Referral Program to Implement Evidence-Based Depression Care. AB - BACKGROUND: Screening and referral for geriatric depression by service agencies is associated with poor treatment engagement indicating the need to transform services to directly provide depression care. OBJECTIVE: To describe a multi organization workgroup implementation planning process used to transform a community-based screening and referral program to provide a brief evidence-based intervention for older adults with depressive symptoms. METHODS: An iterative implementation procedure used by a multi-stakeholder group that selected an evidence-based practice, planned implementation rollout, planned counselor training, and designed an implementation evaluation. RESULTS: The workgroup successfully followed the implementation procedure and developed a plan for the implementation of an evidence-based intervention. Overall, the workgroup prioritized decisions that favored feasibility and low implementation burden. CONCLUSION: A multi-organization workgroup can benefit from a semi-structured implementation planning procedure because it provides all stakeholders with a shared roadmap for implementation planning. PMID- 26849163 TI - Satisfaction with cancer care among underserved racial-ethnic minorities and lower-income patients receiving patient navigation. AB - BACKGROUND: Patient navigation is a barrier-focused program of care coordination designed to achieve timely and high-quality cancer-related care for medically underserved racial-ethnic minorities and the poor. However, to the authors' knowledge, few studies to date have examined the relationship between satisfaction with navigators and cancer-related care. METHODS: The authors included data from 1345 patients with abnormal cancer screening tests or a definitive cancer diagnosis who participated in the Patient Navigation Research Program to test the efficacy of patient navigation. Participants completed demographic questionnaires and measures of patient satisfaction with cancer related care (PSCC) and patient satisfaction with interpersonal relationship with navigator (PSN-I). The authors obtained descriptive statistics to characterize the sample and conducted regression analyses to assess the degree of association between PSN-I and PSCC, controlling for demographic and clinical factors. Analyses of variance were conducted to examine group differences controlling for statistically significant covariates. RESULTS: Statistically significant relationships were found between the PSCC and PSN-I for patients with abnormal cancer screening tests (1040 patients; correlation coefficient (r), 0.4 [P<.001]) and those with a definitive cancer diagnosis (305 patients; correlation coefficient, 0.4 [P<.001]). The regression analysis indicated that having an abnormal colorectal cancer screening test in the abnormal screening test group and increased age and minority race-ethnicity status in the cancer diagnosis group were associated with a higher satisfaction with cancer care (P<.01). CONCLUSIONS: Satisfaction with navigators appears to be significantly associated with satisfaction with cancer-related care. Information regarding the patient navigator relationship should be integrated into patient navigation programs to maximize the likelihood of reducing caner disparities and mortality for medically underserved racial-ethnic minorities and the poor. PMID- 26849169 TI - Confirmation of PDZD7 as a Nonsyndromic Hearing Loss Gene. AB - OBJECTIVE: PDZD7 was identified in 2009 in a family with apparent nonsyndromic sensorineural hearing loss. However, subsequent clinical reports have associated PDZD7 with digenic Usher syndrome, the most common cause of deaf-blindness, or as a modifier of retinal disease. No further reports have validated this gene for nonsyndromic hearing loss, intuitively calling correct genotype-phenotype association into question. This report describes a validating second case for biallelic mutations in PDZD7 causing nonsyndromic mild to severe sensorineural hearing loss. It also provides detailed audiometric and ophthalmologic data excluding Usher syndrome in both the present proband (proband 1) and the first proband described in 2009 (proband 2). DESIGN: Proband 1 was sequenced using a custom-designed next generation sequencing panel consisting of 151 deafness genes. Bioinformatics analysis and filtering disclosed two PDZD7 sequence variants (c.1648C>T, p.Q550* and c.2107del, p.S703Vfs*20). Segregation testing followed in the family. For both probands, audiograms were collected and analyzed for progressive hearing loss and detailed ophthalmic evaluations were performed including electroretinography. RESULTS: Proband 1 demonstrated a prelingual, nonsyndromic, sensorineural hearing loss that progressed in the higher frequencies between 4 and 9 years old. PDZD7 segregation analysis confirmed biallelic inheritance (compound heterozygosity). Mutation analysis determined the c.1648C>T mutation as novel and reported the c.2107del deletion as rs397516633 with a calculated minor allele frequency of 0.000018. Clinical evaluation spanning well over a decade in proband 2 disclosed bilateral, nonprogressive hearing loss. Both probands showed healthy retinas, excluding Usher syndrome-like changes in the eye. CONCLUSIONS: PDZD7 is confirmed as a bona fide autosomal recessive nonsyndromic hearing loss gene. In both probands, there was no evidence of impaired vision or ophthalmic pathology. As the current understanding of PDZD7 mutations bridge Mendelian and complex phenotypes, the authors recommend careful variant interpretation, since PDZD7 is one of many genes associated with both Usher syndrome and autosomal recessive nonsyndromic hearing loss. Additional reports are required for understanding the complete phenotypic spectrum of this gene, including the possibility of high-frequency progression, as well as noise induced hearing loss susceptibility in adult carriers. This report rules out all forms of Usher syndrome with an onset before 12 and 15 years old in probands 1 and 2, respectively. However, due to the young ages of the probands, this report is uninformative regarding older patients. PMID- 26849170 TI - Evaluation of the antineoplastic activity of gallic acid in oral squamous cell carcinoma under hypoxic conditions. AB - The purpose of the current study was to develop and test a theoretical model that could explain the mechanism of action of gallic acid (GA) in the oral squamous cell carcinoma context for the first time. The theoretical model was developed using bioinformatics and interaction network analysis to evaluate the effect of GA on oral squamous cell carcinoma. In a second step to confirm theoretical results, migration, invasion, proliferation, and gene expression (Col1A1, E cadherin, HIF-1alpha, and caspase-3) were performed under normoxic and hypoxic conditions. Our study indicated that treatment with GA resulted in the inhibition of cell proliferation, migration, and invasion in neoplastic cells. Observation of the molecular mechanism showed that GA upregulates E-cadherin expression and downregulates Col1A1 and HIF-1alpha expression, suggesting that GA might be a potential anticancer compound. In conclusion, the present study demonstrated that GA significantly reduces cell proliferation, invasion, and migration by increasing E-cadherin and repressing Col1A1. PMID- 26849171 TI - Do biomarkers of exposure and effect correlate with internal exposure to PAHs in swine? AB - Humans are commonly exposed to polycyclic aromatic hydrocarbons (PAHs), a family of compounds present as mixtures in the environment. This study exposed swine to PAH mixtures in single and subacute dose regimens and collected liver and ileum tissue to measure cytochrome P450 mRNA expression and enzyme activity as biomarkers of exposure and DNA adducts and oxidized proteins as biomarkers of effect. Micronucleated reticulocytes were measured as systemic biomarkers of effect. Duration of exposure did not influence biomarkers of exposure, though exposure duration produced significant increases in DNA adducts and oxidative stress. Micronucleated reticulocyte numbers were not affected by exposure length. PMID- 26849173 TI - Optimization of large-ring cyclodextrin production from starch by amylomaltase from Corynebacterium glutamicum and effect of organic solvent on product size. AB - AIMS: To increase yield of starch conversion to large-ring cyclodextrins (LR-CDs) by amylomaltase from Corynebacterium glutamicum (CgAM). METHODS AND RESULTS: In this work, LR-CDs produced from pea, tapioca, corn, potato, rice and glutinous rice starch by the recombinant CgAM were analysed by High-Performance Anion Exchange Chromatography Using Pulsed Amperometric Detection (HPAEC-PAD). Among these, pea starch gave the highest yield of LR-CDs. Pretreatment of pea starch with isoamylase prior to incubation with CgAM resulted in the increase in LR-CD products by 20%. Surprisingly, CgAM converted starch into LR-CDs within a wide pH range (pH 5.5-9.0). LR-CD syntheses at alkaline pH or at a long incubation time favoured low-degree of polymerization (DP) products (CD22-CD32). Addition of 5 15% dimethyl sulfoxide (DMSO) promoted the synthesis of medium-DP species (CD33 CD43) by 10-25%. CONCLUSIONS: Pretreatment of pea starch with isoamylase could enhance the yield of LR-CDs. The ratio of LR-CD products depends on pH, incubation time and addition of organic solvents such as DMSO. SIGNIFICANCE AND IMPACT OF THE STUDY: LR-CD yield can be increased by thorough optimization of starch types, starch concentrations, enzyme activities, pH and incubation times. This study is the first report of the effect of organic solvents on LR-CD production by amylomaltase. PMID- 26849172 TI - An analysis of 1505 consecutive patients receiving continuous interscalene analgesia at home: a multicentre prospective safety study. AB - Continuous interscalene brachial plexus block has been shown to be the most effective analgesic technique following shoulder surgery; however, its use is uncommon due to logistical and safety concerns related to ambulatory administration. We prospectively studied 1505 consecutive patients undergoing shoulder surgery who received continuous interscalene analgesia at home. Catheter removal was by the patient between postoperative days two and five. There were no major complications although 27% of patients reported mild dyspnoea, 13% hoarseness and 7% dysphagia. Twelve percent sought medical advice and 2% reported technical issues with the pump or tubing. Complications and technical issues were associated with patient age; weight; use of ultrasound or concomitant nerve stimulation as the endpoint for final needle tip position; local anaesthetic placement via the catheter or needle; whether a catheter-related intervention for pain relief was required in the recovery area; and the type of ambulatory pump. We conclude that this study supports the safety of this underused analgesic technique. PMID- 26849174 TI - Facile Synthesis of Nitrogen-Containing Mesoporous Carbon for High-Performance Energy Storage Applications. AB - Porous carbon with high specific surface area (SSA), a reasonable pore size distribution, and modified surface chemistry is highly desirable for application in energy storage devices. Herein, we report the synthesis of nitrogen-containing mesoporous carbon with high SSA (1390 m(2) g(-1)), a suitable pore size distribution (1.5-8.1 nm), and a nitrogen content of 4.7 wt % through a facile one-step self-assembly process. Owing to its unique physical characteristics and nitrogen doping, this material demonstrates great promise for application in both supercapacitors and encapsulating sulfur as a superior cathode material for lithium-sulfur batteries. When deployed as a supercapacitor electrode, it exhibited a high specific capacitance of 238.4 F g(-1) at 1 A g(-1) and an excellent rate capability (180 F g(-1), 10 A g(-1)). Furthermore, when an NMC/S electrode was evaluated as the cathode material for lithium-sulfur batteries, it showed a high initial discharge capacity of 1143.6 mA h g(-1) at 837.5 mA g(-1) and an extraordinary cycling stability with 70.3% capacity retention after 100 cycles. PMID- 26849175 TI - Influence of climate on the survivorship of neonatal red pandas in captivity. AB - Red pandas, Ailurus fulgens, are popular exhibit animals in zoos. It is clear from data in the global studbook that there is considerable variation in their breeding success in different zoos. Population managers have long suspected that environmental temperature plays a key role in these differences. It is generally thought that this species, which is so well adapted to life in the cold damp climate of the mid-altitude forests of the Himalayas, has a problem coping with warmer climates. However, this hypothesis has not been tested until now. Using data extracted from the global studbook, we have demonstrated that climate at the location of birth has a clear impact on the survival of infant red pandas. PMID- 26849177 TI - Practicing handoffs early: Applying a clinical framework in the anatomy laboratory. AB - The anatomy laboratory provides an ideal environment for the integration of clinical contexts as the willed-donor is often regarded as a student's "first patient." This study evaluated an innovative approach to peer teaching in the anatomy laboratory using a clinical handoff context. The authors introduced the "Situation, Background, Assessment, Recommendation" (SBAR) handoff framework within the anatomy laboratory. Study participants included 147 second-year medical students completing the head and neck portion of an anatomy course. The authors used mixed methods to evaluate the impact of the anatomic SBAR on the student anatomy laboratory experience. Qualitative analysis of student evaluations revealed three themes which emerged from students' summaries of their anatomic handoff experiences: Learning-by-teaching; Acquiescing to doing more with less; and Distrust of the peer handoff process. All the themes demonstrated that the anatomic handoff encouraged students' focus on the knowledge preparation and reflection. Closed question analysis suggested that that students' perceptions of handoff usefulness were tied to deeper learning strategies. The handoff provided a mechanism for promoting students' focus on anatomical relationships and facilitated students' learning of transferable clinical skills. Together, these results suggest that the introduction of a handoff process in anatomy education provided both a mechanism for learning anatomy and a unique opportunity for early exposure to an essential clinical skill. This clinical and basic science integration may serve as a vertical integration thread which can be woven throughout undergraduate medical education. Future study will focus on exploring the long-term impacts and learning outcomes of this integration. Anat Sci Educ 9: 476-487. (c) 2016 American Association of Anatomists. PMID- 26849176 TI - Effects of Maternal Mental Health on Engagement in Favorable Health Practices During Pregnancy. AB - INTRODUCTION: A woman's health practices during pregnancy are associated with maternal and neonatal outcomes. Yet limited research has examined predictors of a woman's engagement in favorable health practices, particularly in pregnant women at greatest risk for adverse outcomes. We examined the role of mental health on engagement in favorable health practices during pregnancy in a sample of pregnant, low-income, predominantly African American women. METHODS: A convenience sample of pregnant women was obtained from 3 obstetric clinics within a large Mid-Atlantic academic health system. Pregnant women (N = 166) completed measures of depression, social support, and engagement in favorable health practices during their second trimester. Six domains of health practices (ie, balance of rest and exercise, safety measures, nutrition, substance use, health care access, access to pregnancy-related information) were assessed by the Health Practices in Pregnancy Questionnaire-II. Multiple linear regression was used to examine predictors of engagement in favorable health practices. RESULTS: Fifty nine percent of the study participants experienced depressive symptomatology during pregnancy. Multivariate linear regression modeling demonstrated that increased depressive symptoms, decreased social support, young age, and prepregnancy overweight or obesity were significant predictors of nonengagement in favorable health practices during pregnancy. DISCUSSION: Findings suggest that pregnant women with poor mental health (eg, depressive symptomatology, poor social support) and specific sociodemographic characteristics (eg, young age, prepregnancy overweight or obesity) were less likely to engage in favorable health practices during pregnancy. Health care providers are uniquely positioned to assess a woman's mental health and related indicators to optimize pregnancy and neonatal outcomes. PMID- 26849178 TI - Epidemiological Evidence for a Decreasing Incidence of Neonatal Abstinence Syndrome, 2000-11. AB - BACKGROUND: This study analyses the incidence of Neonatal Abstinence Syndrome (NAS) in a large geographically defined population in Australia. METHOD: Database linkage analysis of all births between 2000 and 2011 in New South Wales (NSW), Australia. The diagnosis of NAS was derived from hospital coding P96.1, 'Neonatal withdrawal symptoms from maternal use of drugs of addiction'. Temporal trends were studied by comparing epoch 1 (2000-05) with epoch 2 (2006-11). The relationship with changes in maternal factors was further analysed. RESULTS: The NAS was coded in 3842 of 1 022 263 live born infants (0.38%). NAS incidence peaked at 5.07 per 1000 live births in 2002, decreasing to 3.18 in 2011 and was negatively correlated with maternal age (r = -0.7). The rate of NAS in epoch 2 (3.4 per 1000 births, 95% CI 3.28, 3.58) was significantly lower than in epoch 1 (4.1 per 1000 births, 95% CI 3.96, 4.33). Epoch 2 mothers were significantly older (mean 29.8 years vs. 28.3 years), less likely to be multiparous (OR 0.7, 95% CI 0.6, 0.9) or smoke (OR 0.4, 95% CI 0.4, 0.5). They were more likely to engage in antenatal care earlier (mean first visit: 14.1 vs. 18.9 weeks). Most infants (~80%) were born at term (>37 weeks gestation). CONCLUSION: The incidence of NAS as a discharge diagnosis has decreased in our population since 2002. Mothers are also older and engaging earlier in prenatal care. Whether these changes alter NAS presentation and diagnosis or whether pregnant women are using drugs that do not cause typical NAS (e.g. amphetamines) is uncertain and requires further study. PMID- 26849180 TI - De novo assembly and characterization of leaf and floral transcriptomes of the hybridizing bromeliad species (Pitcairnia spp.) adapted to Neotropical Inselbergs. AB - We present the leaf and floral transcriptomes of two hybridizing bromeliad species that differ in their major pollinator systems. Here we identified candidate genes responsible for pollinator attraction and reproductive isolation in these two species. We searched for candidate genes involved in floral traits, such as colour. Approximately 34 Gbp of cDNA sequence data were produced from both tissues and species, resulting in a total of 424 506 914 raw reads. The de novo-assembled transcriptomes consisted of a total of 263 955 contigs, further clustered into 110 977 unigenes. Over 58% of the unigenes were functionally annotated and assigned to one or more Gene Ontology terms. The transcriptomes revealed 144 unique transcripts that encode key enzymes in the flavonoid and anthocyanin biosynthesis pathways. The domain/family annotation and phylogenetic analysis allowed us to infer, by homology, potential functions of the genes encoding MYB, HD-ZIP and bZIP-HY5 transcription factors, as well as WD40 protein, which may be involved in anthocyanin and flavonoid regulation in these species. These candidate genes are associated with natural regulation in flower colour in other plant species and will facilitate future studies aimed at elucidating the molecular basis of adaptive differentiation and the evolution of mechanisms of pollinator-mediated reproductive isolation in these two bromeliads. In addition, we identified a total of 49 439 microsatellite loci. These resources will assist future research into adaptation and speciation events in bromeliad species, thus providing a starting point for investigation of the molecular mechanisms of the traits responsible for their reproductive isolation. PMID- 26849182 TI - 3D TOCSY-HSQC NMR for Metabolic Flux Analysis Using Non-Uniform Sampling. AB - (13)C-Metabolic Flux Analysis ((13)C-MFA) is rapidly being recognized as the authoritative method for determining fluxes through metabolic networks. Site specific (13)C enrichment information obtained using NMR spectroscopy is a valuable input for (13)C-MFA experiments. Chemical shift overlaps in the 1D or 2D NMR experiments typically used for (13)C-MFA frequently hinder assignment and quantitation of site-specific (13)C enrichment. Here we propose the use of a 3D TOCSY-HSQC experiment for (13)C-MFA. We employ Non-Uniform Sampling (NUS) to reduce the acquisition time of the experiment to a few hours, making it practical for use in (13)C-MFA experiments. Our data show that the NUS experiment is linear and quantitative. Identification of metabolites in complex mixtures, such as a biomass hydrolysate, is simplified by virtue of the (13)C chemical shift obtained in the experiment. In addition, the experiment reports (13)C-labeling information that reveals the position specific labeling of subsets of isotopomers. The information provided by this technique will enable more accurate estimation of metabolic fluxes in large metabolic networks. PMID- 26849184 TI - Gelucire and Gelucire-PEG400 formulations; tolerability in species used for non clinical safety testing after oral (gavage) dosing. AB - The selection of a vehicle for oral formulations of compounds to be used in non clinical safety studies is a challenge for poorly soluble compounds. Typically a compromise between solubility and tolerability has to be reached. Vehicle tolerability data are not readily available for a number of vehicles, and a series of oral tolerability studies were, therefore, conducted with Gelucire and Gelucire:PEG400 formulations in rats, dogs and minipigs in order to determine tolerable daily dose volumes in these species. Gelucire and Gelucire:PEG400 formulations were assessed in studies for up to 5 days in minipigs, 7 days in rats and up to 39 weeks in dogs. Gastrointestinal side effects in terms of soft and/or liquid faeces were noted in all species, but the sensitivity to these effects differed between species with the dog being the most sensitive. It was concluded that Gelucire:PEG400 (90:10) was tolerated in Beagle dogs when administered at 1 ml kg(-1) once daily for 39 weeks, and 100% Gelucire was tolerated in the rat and the minipig when administered once daily at 5 ml kg(-1) for 5 days. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26849185 TI - Quantification of pravastatin acid, lactone and isomers in human plasma by UHPLC MS/MS and its application to a pediatric pharmacokinetic study. AB - An ultra high pressure liquid chromatography-tandem mass spectrometric (UHPLC MS/MS) method for the simultaneous quantitation of pravastatin and major metabolites, 3'alpha-hydroxy-pravastatin, pravalactone and 3'alpha-hydroxy pravalactone, in human plasma has been developed and validated. Aliquots of (100MUL) plasma in EDTA were diluted in pH 4.5 (0.1M buffer) to stabilize the analytes and subjected to hydrophilic lipophilic balance (HLB) solid phase extraction on 96 well MUelution plates. Extracted samples were evaporated to dryness and reconstituted in pH 4.5 buffer. Chromatographic separation was performed on a CortecsTM C18 column (2.1*100mm, 1.8MUm), using gradient elution with a blend of acetonitrile and 10mM methylammonium acetate buffer (pH 4.5) at a flow rate of 0.4mL/min. Mass spectrometric detection was performed using multiple reaction monitoring (MRM) switching between positive/negative electrospay ionization (ESI). Pravastatin, 3'alpha-hydroxy-pravastatin, and internal standards [(2)H3]-pravastatin, and [(2)H3]-3'alpha-hydroxy-pravastatin were monitored in negative ESI mode at ion transitions m/z 423.2->321.1 and 426.2 >321.1, respectively. Positive ESI mode was used for the detection of pravalactone, 3'alpha-hydroxy-pravalactone, and internal standards [(2)H3] pravalactone, and [(2)H3]-3'alpha-hydroxy-pravalactone at ion transitions m/z 438.2->183.1 and 441.2->269.1 respectively. The method was linear for all analytes in the concentration range 0.5-200nM with intra- and inter-day precisions (as relative standard deviation) of <=5.2% and accuracy (as relative error) of <=8.0% at all quality control levels. The method was successfully applied to the investigation of pharmacokinetic properties of pravastatin and its metabolites in children after an oral dose of 20-40mg. PMID- 26849186 TI - Use of capillary electrophoresis with dual-opposite end injection for simultaneous analysis of small ions in saliva samples from wrestlers undergoing a weight training program. AB - Capillary electrophoresis-capacitively coupled contactless conductivity detection (CE-C4D), conducted using an in-house-developed polyvinyl alcohol (PVA)-coated capillary system, was applied for the simultaneous analysis of small anions and cations in saliva samples from wrestlers undergoing a weight training program. Use of the PVA capillary for CE provided good reproducible ion separation with minimization of the electroosmotic flow and suppression of protein adsorption onto the capillary wall. Four cations and eight anions were separated in 12min, using a background electrolyte of 20mM MES/20mM histidine and 18-crown-6 ether (pH 6) at 20kV. The relative standard deviations (n=5) of the migration times and peak areas were <1% and <8%, respectively. The detection limit at a signal-to noise ratio of 3 ranged from 1.6 to 10MUM. Using the optimized CE-C4D system, we investigated the correlations between the concentrations of salivary ions and cortisol, which is commonly used as a stress marker. Analysis of saliva samples from ten wrestlers, who were attempting rapid weight loss before a competition, showed the following trends: (1) all ion concentrations, except for Ca(2+), Na(+), and Cl(-), increased between the first and last days of weight loss; (2) Mg(2+) increased to 166% (from 0.50mM to 1.4mM) between the first and last days of weight loss, being the highest increase of all the ions; and (3) K(+), Mg(2+), NO3(-), and SCN(-) levels were strongly correlated (P<0.05) with cortisol. The CE C4D rapidly produced useful data on saliva ion contents, with good ion recovery as determined by the standard addition method (89-110%). PMID- 26849187 TI - Adsorption isotherms, kinetics and thermodynamic studies towards understanding the interaction between cross-linked alginate-guar gum matrix and chymotrypsin. AB - The adsorption kinetics of chymotrypsin, a pancreatic serine protease, onto an alginate-gum guar matrix cross-linked with epichlorohydrin has been performed using a batch-adsorption technique. The effect of various experimental parameters such as pH, salt presence, contact time and temperature were investigated. The pseudo-first-order and pseudo-second-order kinetic models were used to describe the kinetic data which shows that the adsorption of the enzyme followed the pseudo-second-order rate expression. The Langmuir, Freundlich and Hill adsorption isotherm models were applied to describe the equilibrium isotherms, and the isotherm constants were determined. It was found that Hill model was more suitable for our data because the isotherm data showed a sigmoidal behavior with the free enzyme concentration increasing in equilibrium. At 8 degrees C and at pH 5.0, 1g hydrate matrix adsorbed about 7mg of chymotrypsin. In the desorption process 80% of the biological activity of chymotrypsin was recovered under the condition of 50mM phosphate buffer, pH 7.00-500mM NaCl. When successive cycles of adsorption/washing/desorption were performed, it was observed that the matrix remained functional until the fourth cycle of repeated batch enzyme adsorption. These results are important in terms of diminishing of cost and waste generation. PMID- 26849183 TI - Noninvasive brain stimulation treatments for addiction and major depression. AB - Major depressive disorder (MDD) and substance use disorders (SUDs) are prevalent, disabling, and challenging illnesses for which new treatment options are needed, particularly in comorbid cases. Neuroimaging studies of the functional architecture of the brain suggest common neural substrates underlying MDD and SUDs. Intrinsic brain activity is organized into a set of functional networks, of which two are particularly relevant to psychiatry. The salience network (SN) is crucial for cognitive control and response inhibition, and deficits in SN function are implicated across a wide variety of psychiatric disorders, including MDD and SUDs. The ventromedial network (VMN) corresponds to the classic reward circuit, and pathological VMN activity for drug cues/negative stimuli is seen in SUDs/MDD. Noninvasive brain stimulation (NIBS) techniques, including rTMS and tDCS, have been used to enhance cortico-striatal-thalamic activity through the core SN nodes in the dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and anterior insula. Improvements in both MDD and SUD symptoms ensue, including in comorbid cases, via enhanced cognitive control. Inhibition of the VMN also appears promising in preclinical studies for quenching the pathological incentive salience underlying SUDs and MDD. Evolving techniques may further enhance the efficacy of NIBS for MDD and SUD cases that are unresponsive to conventional treatments. PMID- 26849188 TI - Alignment and Graphene-Assisted Decoration of Lyotropic Chromonic Liquid Crystals Containing DNA Origami Nanostructures. AB - Composites of DNA origami nanostructures dispersed in a lyotropic chromonic liquid crystal are studied by polarizing optical microscopy. The homogeneous aqueous dispersions can be uniformly aligned by confinement between two glass substrates, either parallel to the substrates owing to uniaxial rubbing or perpendicular to the substrates using ozonized graphene layers. These opportunities of uniform alignment may pave the way for tailored anisometric plasmonic DNA nanostructures to photonic materials. In addition, a decorated texture with nonuniform orientation is observed on substrates coated with pristine graphene. When the water is allowed to evaporate slowly, microscopic crystal needles appear, which are aligned along the local orientation of the director. This decoration method can be used for studying the local orientational order and the defects in chromonic liquid crystals. PMID- 26849189 TI - Polysaccharides as Alternative Moisture Retention Agents for Shrimp. AB - Phosphates are used as moisture retention agents (MRAs) by the shrimp industry. Although they are effective, phosphates are expensive, need to be listed on a food label, and overuse can often lead to a higher product cost for consumers. Polysaccharides were researched as alternative MRAs. Polysaccharides are usually inexpensive, are considered natural, and can have nutritional benefits. Research was conducted to determine whether polysaccharides yielded similar functional impacts as phosphates. Treatments included a 0.5% fibercolloid solution isolated from citrus peel, an 8% pectin solution, a 0.5% xanthan gum (XG) solution, a 1% carboxymethyl cellulose solution, and conventionally used 4% sodium tripolyphosphate (STP). Experimental treatments were compared to a distilled water control to gauge effectiveness. Freezing, boiling, and oven drying studies were performed to determine how moisture retention in shrimp differed using these different treatments. Water activity was measured to determine any potential differences in shelf life. Solution uptake was also determined to understand how well the treatments enhanced water binding. For moisture loss by freezing, 4% STP and the 0.5% fibercolloid solution functioned the best. The 4% STP treated shrimp lost the least amount of moisture during boiling. The 0.5% fibercolloid and 0.5% XG treatment outperformed phosphates in respect to moisture uptake ability. None of the treatments had a major effect on water activity. All treatments were rated similar in consumer sensory acceptability tests except for pectin, which was rated lower by the sensory panel. Overall, polysaccharides were found to be viable alternatives to phosphates. PMID- 26849190 TI - To Cut or Not to Cut: Discovery of a Novel Regulator of DNA Break Resection. AB - Nucleolytic resection of DNA double-strand breaks is the crucial first step in their repair via homologous recombination. New findings by Tkac et al. (2016) published in this issue of Molecular Cell identify HELB as a novel, cell-cycle specific negative regulator of DNA end resection. PMID- 26849191 TI - ADPr-ChAP: Mapping ADP-Ribosylation onto the Genome. AB - In this issue of Molecular Cell, Bartolomei et al. (2016) describe a chromatin affinity precipitation method using well-characterized ADP-ribose binding domains to provide the first genome-wide view of ADP-ribosylated chromatin. Here, we discuss its potential applications and the remaining challenges ahead. PMID- 26849193 TI - Heterogeneous adsorption behavior of landfill leachate on granular activated carbon revealed by fluorescence excitation emission matrix (EEM)-parallel factor analysis (PARAFAC). AB - Heterogeneous adsorption behavior of landfill leachate on granular activated carbon (GAC) was investigated by fluorescence excitation-emission matrix (EEM) combined with parallel factor analysis (PARAFAC). The equilibrium adsorption of two leachates on GAC was well described by simple Langmuir and Freundlich isotherm models. More nonlinear isotherm and a slower adsorption rate were found for the leachate with the higher values of specific UV absorbance and humification index, suggesting that the leachate containing more aromatic content and condensed structures might have less accessible sites of GAC surface and a lower degree of diffusive adsorption. Such differences in the adsorption behavior were found even within the bulk leachate as revealed by the dissimilarity in the isotherm and kinetic model parameters between two identified PARAFAC components. For both leachates, terrestrial humic-like fluorescence (C1) component, which is likely associated with relatively large sized and condensed aromatic structures, exhibited a higher isotherm nonlinearity and a slower kinetic rate for GAC adsorption than microbial humic-like (C2) component. Our results were consistent with size exclusion effects, a well-known GAC adsorption mechanism. This study demonstrated the promising benefit of using EEM-PARAFAC for GAC adsorption processes of landfill leachate through fast monitoring of the influent and treated leachate, which can provide valuable information on optimizing treatment processes and predicting further environmental impacts of the treated effluent. PMID- 26849192 TI - Synonymous Codons Direct Cotranslational Folding toward Different Protein Conformations. AB - In all genomes, most amino acids are encoded by more than one codon. Synonymous codons can modulate protein production and folding, but the mechanism connecting codon usage to protein homeostasis is not known. Here we show that synonymous codon variants in the gene encoding gamma-B crystallin, a mammalian eye-lens protein, modulate the rates of translation and cotranslational folding of protein domains monitored in real time by Forster resonance energy transfer and fluorescence-intensity changes. Gamma-B crystallins produced from mRNAs with changed codon bias have the same amino acid sequence but attain different conformations, as indicated by altered in vivo stability and in vitro protease resistance. 2D NMR spectroscopic data suggest that structural differences are associated with different cysteine oxidation states of the purified proteins, providing a link between translation, folding, and the structures of isolated proteins. Thus, synonymous codons provide a secondary code for protein folding in the cell. PMID- 26849194 TI - Electrochemical degradation of pyridine by Ti/SnO2-Sb tubular porous electrode. AB - Diffusion in electrochemistry is a critical issue for water purification. Electrocatalytic reactor system in improving water quality is a useful way to induce convection to enhance diffusion. This study focuses on the preparation and the characterization of Ti/SnO2-Sb tubular porous electrode for degrading pyridine wastewater. The electrode as an anode in reactor system is prepared by coating SnO2-Sb as an electro-catalyst via Pechini method on the tubular porous Ti. Scanning Electron Microscopy, Energy Dispersive Spectrum, X-ray Diffraction and Pore Distribution are employed to evaluate the structure and morphology of the electrodes coatings, and Linear Sweep Voltammetry and Cyclic Voltammetry are used to illustrate the electrochemical properties of the electrodes coatings. Furthermore, the electrochemical oxidation performance of Ti/SnO2-Sb tubular porous electrode is characterized by degrading pyridine wastewater. The effects of flow and static pattern, initial pyridine concentration, supporting electrolyte concentration, current density and pH on the performance of the reactor were investigated in the electrocatalytic reactor system. The results indicated that the removal ratio of pyridine reaches maximum which is 98% under the optimal operation conditions, that are 100 mg L(-1) initial pyridine concentration, 10 g L(-1) supporting electrolyte concentration, 30 mA cm(-2) current density and pH 3. Transition state calculation based on the density function theory was combined with High Performance Liquid Chromatography, Gas Chromatography and Ionic Chromatography results to describe the pathway of pyridine degradation. PMID- 26849195 TI - Role of bentonite clays on cell growth. AB - Bentonites, naturally occurring clays, are produced industrially because of their adsorbent capacity but little is known about their effects on human health. This manuscript reports on the effect of bentonites on cell growth behaviour. Bentonites collected from India (Bent-India), Hungary (Bent-Hungary), Argentina (Bent-Argentina), and Indonesia (Bent-Indonesia) were studied. All four bentonites were screened in-vitro against two human cancer cell lines [U251 (central nervous system, glioblastoma) and SKLU-1 (lung adenocarcinoma)] supplied by the National Cancer Institute (USA). Bentonites induced growth inhibition in the presence of U251 cells, and growth increment in the presence of SKLU-1 cells, showing that interactions between bentonite and cell surfaces were highly specific. The proliferation response for U251 cells was explained because clay surfaces controlled the levels of metabolic growth components, thereby inhibiting the development of high-grade gliomas, particularly primary glioblastomas. On the other hand, the proliferation response for SKLU-1 was explained by an exacerbated growth favoured by swelling, and concomitant accumulation of solutes, and their hydration and transformation via clay-surface mediated reactions. PMID- 26849196 TI - Laboratory study of PCB transport from primary sources to settled dust. AB - Dust is an important sink for indoor air pollutants, such as polychlorinated biphenyls (PCBs) that were used in building materials and products. In this study, two types of dust, house dust and Arizona Test Dust, were tested in a 30 m(3) stainless steel chamber with two types of panels. The PCB-containing panels were aluminum sheets coated with a PCB-spiked primer or caulk. The PCB-free panels were coated with the same materials but without PCBs. The dust evenly spread on each panel was collected at different times to determine its PCB content. The data from the PCB panels were used to evaluate the PCB migration from the source to the dust through direct contact, and the data from the PCB free panels were used to evaluate the sorption of PCBs through the dust/air partition. Settled dust can adsorb PCBs from air. The sorption concentration was dependent on the congener concentration in the air and favored less volatile congeners. When the house dust was in direct contact with the PCB-containing panel, PCBs migrated into the dust at a much faster rate than the PCB transfer rate due to the dust/air partition. The dust/source partition was not significantly affected by the congener's volatility. For a given congener, the ratio between its concentration in the dust and in the source was used to estimate the dust/source partition coefficient. The estimated values ranged from 0.04 to 0.16. These values are indicative of the sink strength of the tested house dust being in the middle or lower-middle range. PMID- 26849197 TI - Formation and toxicity of halogenated disinfection byproducts resulting from linear alkylbenzene sulfonates. AB - Linear alkylbenzene sulfonates (LAS) are an important group of organic pollutants in urban wastewater effluents. The practice of using seawater for toilet flushing results in saline wastewater effluents, which contain high levels of bromide ions. Chlorine is most commonly used in wastewater disinfection. During chlorination of freshwater or saline wastewater effluents, some halogenated disinfection byproducts (DBPs) resulting from LAS could be formed. In this study, the overall formation of halogenated DBPs resulting from LAS was quantified by total organic halogen (TOX) measurement. Polar halogenated DBPs resulting from LAS were detected with a novel precursor ion scan method. The structures and formation pathways of the major ones were tentatively proposed. The overall toxicity of different scenarios of LAS samples was evaluated with embryos of a marine polychaete Platynereis dumerilii. The results demonstrate that chlorinated DBPs were generated during chlorination of LAS without bromide, while brominated DBPs were generated during chlorination of LAS with bromide. The TOX concentrations were relatively low, indicating that LAS were not quite reactive with halogen. The major polar chlorinated and brominated DBPs resulting from LAS were proposed to be 2,6-dichloro-3,5-dihydroxy-4-dodecylbenzenesulfonic acid and 2,6-dibromo-3,5-dihydroxy-4-dodecylbenzenesulfonic acid, which belong to a group of DBPs with similar structures but different halogen atoms, and their formation pathways were tentatively proposed. The results also reveal that the undisinfected LAS sample was the least toxic, followed by the chlorinated LAS sample without bromide, and the chlorinated LAS sample with bromide was the most toxic. PMID- 26849198 TI - Is the chronic impact of sulfamethoxazole different for slow growing culture? The effect of culture history. AB - The study evaluated impact of sulfamethoxazole on acetate utilization kinetics and microbial community structure using respirometric analysis and pyrosequencing. A fill and draw reactor fed with acetate was sustained at a sludge age of 10 days. Acute impact was assessed by modeling of respirometric data in batch reactors started with sulfamethoxazole doses in the range of 25-200 mg/L. Fill and draw operation resumed with continuous sulfamethoxazole dosing of 50 mg/L and the chronic impact was evaluated with acclimated biomass after 20 days. Acute impact revealed higher maintenance energy requirements, activity reduction and slight substrate binding. Chronic impact resulted in retardation of substrate storage. A fraction of acetate was utilized at a much lower rate with partial biodegradation of sulfamethoxazole by the acclimated biomass. Pyrosequencing indicated that Amaricoccus sp. and an unclassified Bacteroidetes sp., possibly with the ability to co-metabolize sulfamethoxazole, dominated the community. PMID- 26849199 TI - Butanol fermentation from microalgae-derived carbohydrates after ionic liquid extraction. AB - Lipid extracted algae (LEA) is an attractive feedstock for alcohol fuel production as it is a non-food crop which is largely composed of readily fermented carbohydrates like starch rather than the more recalcitrant lignocellulosic materials currently under intense development. This study compares the suitability of ionic liquid extracted algae (ILEA) and hexane extracted algae (HEA) for acetone, butanol, and ethanol (ABE) fermentation. The highest butanol titers (8.05 g L(-1)) were achieved with the fermentation of the acid hydrolysates of HEA, however, they required detoxification to support product formation after acid hydrolysis while ILEA did not. Direct ABE fermentation of ILEA and HEA (without detoxification) starches resulted in a butanol titer of 4.99 and 6.63 g L(-1), respectively, which significantly simplified the LEA to butanol process. The study demonstrated the compatibility of producing biodiesel and butanol from a single feedstock which may help reduce the feedstock costs of each individual process. PMID- 26849200 TI - Effect of acid pretreatment on different parts of corn stalk for second generation ethanol production. AB - In this study, the effects of different parts of corn stalk, including stem, leaf, flower, cob and husk on second generation ethanol production were evaluated. FTIR, XRD and SEM were performed to investigate the effect of dilute acid pretreatment. The bagasse obtained after pretreatment were further hydrolyzed by cellulase and used as the substrate for ethanol fermentation. As results, hemicelluloses fractions in different parts of corn stalk were dramatically removed and the solid fractions showed vivid compositions and crystallinities. Compared with other parts of corn stalk, the cob had higher sugar content and better enzymatic digestibility. The highest glucose yield of 94.2% and ethanol production of 24.0 g L(-1) were achieved when the cob was used as feedstock, while the glucose yield and the ethanol production were only 86.0% and 17.1 g L(-1) in the case of flower. PMID- 26849201 TI - Industrial demonstration plant for the gasification of herb residue by fluidized bed two-stage process. AB - A fluidized bed two-stage gasification process, consisting of a fluidized-bed (FB) pyrolyzer and a transport fluidized bed (TFB) gasifier, has been proposed to gasify biomass for fuel gas production with low tar content. On the basis of our previous fundamental study, an autothermal two-stage gasifier has been designed and built for gasify a kind of Chinese herb residue with a treating capacity of 600 kg/h. The testing data in the operational stable stage of the industrial demonstration plant showed that when keeping the reaction temperatures of pyrolyzer and gasifier respectively at about 700 degrees C and 850 degrees C, the heating value of fuel gas can reach 1200 kcal/Nm(3), and the tar content in the produced fuel gas was about 0.4 g/Nm(3). The results from this pilot industrial demonstration plant fully verified the feasibility and technical features of the proposed FB two-stage gasification process. PMID- 26849203 TI - Altered metabolic parameters in association with antipsychotic medication use in diabetes: A population based case-control study. AB - AIMS: This study assess differences in clinical variables in diabetes patients prescribed antipsychotic medication and determines relative schizophrenia prevalence in the diabetes population. METHODS: This population-based case control study utilizing Scotland's national diabetes registry (SCI-diabetes) and linked psychiatric hospital discharge data (SMR04) established diabetes phenotypes in a patient cohort prescribed long term antipsychotic medication (n=2362) (cases). Cases were matched 1:10 to diabetes patients not prescribed antipsychotic medication (controls) for BMI, gender; diabetes type; birth year; diagnosis date; smoking status. Sub-groups with defined schizophrenia (n=196) or bipolar disorder (n=190) were further examined. Schizophrenia prevalence in the diabetes versus general population was compared. RESULTS: During follow up, antipsychotic prescription was associated with lower HbA1c (55.1 (95% CI 54.5 55.8) or 7.2 (95% CI 7.1-7.3)% vs 58.2 (58.0-58.4) mmol or 7.5 (95% CI 7.5-7.5)% p<0.001) lower serum total cholesterol, 4.2 (4.1-4.2) vs 4.3 (4.2-4.3) mmol/l, p<0.001, lower blood pressure (systolic 130 (130.17-131.29) vs 134 (134.3-134.7) mmHg, p<0.001), higher prescription of oral hypoglycaemic medication (42% (40-45) vs 38% (37-39) p<0.001), similar statin prescriptions (85% (81-89) vs 85% (84 86), p=0.55), and lower retinopathy rates (28% (25.6-30.5) vs 32% (31.5-33.1), p<0.001). HbA1c at diagnosis was similar (p=0.27). Schizophrenia prevalence was higher in the diabetes versus general population with differences across age groups (Scottish population versus diabetic population rate of 522.2 (522.1 522.3) versus 717.4 (703.4-731.9) per 100,000). CONCLUSIONS: We confirm higher diabetes rates in schizophrenia up to age 70, similar attendance rates and clinical measurements that are not worse in a large well-matched population-based Scottish sample prescribed antipsychotic medication versus matched general diabetes patients. PMID- 26849204 TI - Internal Domains of Natural Porous Media Revealed: Critical Locations for Transport, Storage, and Chemical Reaction. AB - Internal pore domains exist within rocks, lithic fragments, subsurface sediments, and soil aggregates. These domains, termed internal domains in porous media (IDPM), represent a subset of a material's porosity, contain a significant fraction of their porosity as nanopores, dominate the reactive surface area of diverse media types, and are important locations for chemical reactivity and fluid storage. IDPM are key features controlling hydrocarbon release from shales in hydraulic fracture systems, organic matter decomposition in soil, weathering and soil formation, and contaminant behavior in the vadose zone and groundwater. Traditionally difficult to interrogate, advances in instrumentation and imaging methods are providing new insights on the physical structures and chemical attributes of IDPM, and their contributions to system behaviors. Here we discuss analytical methods to characterize IDPM, evaluate information on their size distributions, connectivity, and extended structures; determine whether they exhibit unique chemical reactivity; and assess the potential for their inclusion in reactive transport models. Ongoing developments in measurement technologies and sensitivity, and computer-assisted interpretation will improve understanding of these critical features in the future. Impactful research opportunities exist to advance understanding of IDPM, and to incorporate their effects in reactive transport models for improved environmental simulation and prediction. PMID- 26849205 TI - Realizing Low-Energy Classification Systems by Implementing Matrix Multiplication Directly Within an ADC. AB - In wearable and implantable medical-sensor applications, low-energy classification systems are of importance for deriving high-quality inferences locally within the device. Given that sensor instrumentation is typically followed by A-D conversion, this paper presents a system implementation wherein the majority of the computations required for classification are implemented within the ADC. To achieve this, first an algorithmic formulation is presented that combines linear feature extraction and classification into a single matrix transformation. Second, a matrix-multiplying ADC (MMADC) is presented that enables multiplication between an analog input sample and a digital multiplier, with negligible additional energy beyond that required for A-D conversion. Two systems mapped to the MMADC are demonstrated: (1) an ECG-based cardiac arrhythmia detector; and (2) an image-pixel-based facial gender detector. The RMS error over all multiplication performed, normalized to the RMS of ideal multiplication results is 0.018. Further, compared to idealized versions of conventional systems, the energy savings obtained are estimated to be 13* and 29*, respectively, while achieving similar level of performance. PMID- 26849202 TI - Magnetic Resonance Imaging-Guided, Open-Label, High-Frequency Repetitive Transcranial Magnetic Stimulation for Adolescents with Major Depressive Disorder. AB - OBJECTIVE: Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression. METHODS: Ten adolescents with treatment-resistant depression were enrolled in an open-label trial of high-frequency rTMS. Participants were offered 30 rTMS sessions (10 Hz, 120% motor threshold, left 3000 pulses applied to the dorsolateral prefrontal cortex) over 6-8 weeks. Coil placement for treatment was MRI guided. The scalp location for treatment was compared with the locations identified with standard 5 cm rule and Beam F3 methods. RESULTS: Seven adolescents completed 30 rTMS sessions. No safety or tolerability concerns were identified. Depression severity as assessed with the Children's Depression Rating Scale Revised improved from baseline to treatment 10, treatment 20, and treatment 30. Gains in depressive symptom improvement were maintained at 6 month follow-up visits. An MRI-guided approach for coil localization was feasible and efficient. Our results suggest that the 5 cm rule, Beam F3, and the MRI-guided localization approaches provided variable scalp targets for rTMS treatment. CONCLUSIONS: Open label, high-frequency rTMS was feasible, tolerable, and effective for adolescents with treatment-resistant depression. Larger, blinded, sham-controlled trials are needed for definitive safety and efficacy data. Further efforts to understand optimal delivery, dosing, and biomarker development for rTMS treatments of adolescent depression are warranted. PMID- 26849206 TI - Classification of vocal fold leukoplakia by clinical scoring. AB - BACKGROUND: Vocal cord leukoplakia comprises a variety of lesions. The purpose of this study was to stratify vocal leukoplakias before surgery. METHODS: Patients with an initial diagnosis of vocal leukoplakia who underwent surgical excision at a tertiary referral center in Taiwan were recruited for this study. Their clinical records, including age, sex, preoperative laryngoscopic images in the office setting, and final pathology reports were collected and analyzed. RESULTS: Patient age (p = .010), nonhomogenous lesion texture (p = .001), and existence of hyperemia (p = .014) were identified as independent factors predicting malignancy. A predictive formula was established accordingly. The model showed an excellent discrimination role by receiver operating characteristic curve analysis (area under the curve = 0.86; p < .001). CONCLUSION: This study confirmed the value of a scoring system based on laryngoscopic characteristics and patient age for predicting the histologic results in vocal leukoplakia. It is helpful for classifying vocal leukoplakia and pretreatment planning. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E1998-E2003, 2016. PMID- 26849207 TI - Integration of Multiple Genomic and Phenotype Data to Infer Novel miRNA-Disease Associations. AB - MicroRNAs (miRNAs) play an important role in the development and progression of human diseases. The identification of disease-associated miRNAs will be helpful for understanding the molecular mechanisms of diseases at the post transcriptional level. Based on different types of genomic data sources, computational methods for miRNA-disease association prediction have been proposed. However, individual source of genomic data tends to be incomplete and noisy; therefore, the integration of various types of genomic data for inferring reliable miRNA-disease associations is urgently needed. In this study, we present a computational framework, CHNmiRD, for identifying miRNA-disease associations by integrating multiple genomic and phenotype data, including protein-protein interaction data, gene ontology data, experimentally verified miRNA-target relationships, disease phenotype information and known miRNA-disease connections. The performance of CHNmiRD was evaluated by experimentally verified miRNA-disease associations, which achieved an area under the ROC curve (AUC) of 0.834 for 5 fold cross-validation. In particular, CHNmiRD displayed excellent performance for diseases without any known related miRNAs. The results of case studies for three human diseases (glioblastoma, myocardial infarction and type 1 diabetes) showed that all of the top 10 ranked miRNAs having no known associations with these three diseases in existing miRNA-disease databases were directly or indirectly confirmed by our latest literature mining. All these results demonstrated the reliability and efficiency of CHNmiRD, and it is anticipated that CHNmiRD will serve as a powerful bioinformatics method for mining novel disease-related miRNAs and providing a new perspective into molecular mechanisms underlying human diseases at the post-transcriptional level. CHNmiRD is freely available at http://www.bio-bigdata.com/CHNmiRD. PMID- 26849208 TI - On the pitfalls of disclosure statements. PMID- 26849210 TI - Correction: Predicting Optimal Outcomes in Cognitive Therapy or Interpersonal Psychotherapy for Depressed Individuals Using the Personalized Advantage Index Approach. PMID- 26849209 TI - Evaluation of the Therapeutic Potential of Anti-TLR4-Antibody MTS510 in Experimental Stroke and Significance of Different Routes of Application. AB - Toll-like receptors (TLRs) are central sensors for the inflammatory response in ischemia-reperfusion injury. We therefore investigated whether TLR4 inhibition could be used to treat stroke in a standard model of focal cerebral ischemia. Anti-TLR4/MD2-antibody (mAb clone MTS510) blocked TLR4-induced cell activation in vitro, as reported previously. Here, different routes of MTS510 application in vivo were used to study the effects on stroke outcome up to 2d after occlusion of the middle cerebral artery (MCAO) for 45 min in adult male C57Bl/6 wild-type mice. Improved neurological performance, reduced infarct volumes, and reduced brain swelling showed that intravascular application of MTS510 had a protective effect in the model of 45 min MCAO. Evaluation of potential long-term adverse effects of anti-TLR4-mAb-treament revealed no significant deleterious effect on infarct volumes nor neurological deficit after 14d of reperfusion in a mild model of stroke (15 min MCAO). Interestingly, inhibition of TLR4 resulted in an altered adaptive immune response at 48 hours after reperfusion. We conclude that blocking TLR4 by the use of specific mAb is a promising strategy for stroke therapy. However, long-term studies with increased functional sensitivity, larger sampling sizes and use of other species are required before a clinical use could be envisaged. PMID- 26849211 TI - Optimising Extinction of Conditioned Disgust. AB - Maladaptive disgust responses are tenacious and resistant to exposure-based interventions. In a similar vein, laboratory studies have shown that conditioned disgust is relatively insensitive to Conditioned Stimulus (CS)-only extinction procedures. The relatively strong resistance to extinction might be explained by disgust's adaptive function to motivate avoidance from contamination threats (pathogens) that cannot be readily detected and are invisible to the naked eye. Therefore, the mere visual presentation of unreinforced disgust eliciting stimuli might not be sufficient to correct a previously acquired threat value of the CS+. Following this, the current study tested whether the efficacy of CS-only exposure can be improved by providing additional safety information about the CS+. For the CSs we included two neutral items a pea soup and a sausage roll, whereas for the Unconditioned Stimulus (US) we used one video clip of a woman vomiting and a neutral one about glass blowing. The additional safety information was conveyed by allowing actual contact with the CS+ or by observing an actress eating the food items representing the CS+. When additional safety information was provided via allowing direct contact with the CS+, there was a relatively strong post extinction increase in participants' willingness-to-eat the CS+. This beneficial effect was still evident at one-week follow up. Also self-reported disgust was lower at one-week follow up when additional safety information was provided. The current findings help explain why disgust is relatively insensitive to CS-only extinction procedures, and provide helpful starting points to improve interventions that are aimed to reduce distress in disgust-related psychopathology. PMID- 26849212 TI - Overexpression of the NDR1/HIN1-Like Gene NHL6 Modifies Seed Germination in Response to Abscisic Acid and Abiotic Stresses in Arabidopsis. AB - NHL (NDR1/HIN1-like) genes play crucial roles in pathogen induced plant responses to biotic stress. Here, we report the possible function of NHL6 in plant response to abscisic acid (ABA) and abiotic stress. NHL6 was highly expressed in non germinated seeds, and its expression was strongly induced by ABA and multiple abiotic stress signals. Loss-of-function of NHL6 decreased sensitivity to ABA in the early developmental stages including seed germination and post-germination seedling growth of the nhl6 mutants. However, overexpression of NHL6 increased sensitivity to ABA, salt and osmotic stress of the transgenic plants. Further studies indicated that the increased sensitivity in the 35S::NHL6 overexpressing plants could be a result of both ABA hypersensitivity and increased endogenous ABA accumulation under the stress conditions. It was also seen that the ABA responsive element binding factors AREB1, AREB2 and ABF3 could regulate NHL6 expression at transcriptional level. Our results indicate that NHL6 plays an important role in the abiotic stresses-induced ABA signaling and biosynthesis, particularly during seed germination and early seedling development in Arabidopsis. PMID- 26849213 TI - Vaccination with the Surface Proteins MUL_2232 and MUL_3720 of Mycobacterium ulcerans Induces Antibodies but Fails to Provide Protection against Buruli Ulcer. AB - BACKGROUND: Buruli ulcer, caused by infection with Mycobacterium ulcerans, is a chronic ulcerative neglected tropical disease of the skin and subcutaneous tissue that is most prevalent in West African countries. M. ulcerans produces a cytotoxic macrolide exotoxin called mycolactone, which causes extensive necrosis of infected subcutaneous tissue and the development of characteristic ulcerative lesions with undermined edges. While cellular immune responses are expected to play a key role against early intracellular stages of M. ulcerans in macrophages, antibody mediated protection might be of major relevance against advanced stages, where bacilli are predominantly found as extracellular clusters. METHODOLOGY/PRINCIPAL FINDINGS: To assess whether vaccine induced antibodies against surface antigens of M. ulcerans can protect against Buruli ulcer we formulated two surface vaccine candidate antigens, MUL_2232 and MUL_3720, as recombinant proteins with the synthetic Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion. The candidate vaccines elicited strong antibody responses without a strong bias towards a TH1 type cellular response, as indicated by the IgG2a to IgG1 ratio. Despite the cross-reactivity of the induced antibodies with the native antigens, no significant protection was observed against progression of an experimental M. ulcerans infection in a mouse footpad challenge model. CONCLUSIONS: Even though vaccine-induced antibodies have the potential to opsonise the extracellular bacilli they do not have a protective effect since infiltrating phagocytes might be killed by mycolactone before reaching the bacteria, as indicated by lack of viable infiltrates in the necrotic infection foci. PMID- 26849215 TI - Medical management of chronic rhinosinusitis - an update. AB - Chronic rhinosinusitis (CRS) is an epidemiologically important, chronic inflammatory disease process affecting the paranasal sinuses with significant and extensively reported economic implications. Despite an elusive pathophysiologic mechanism underlying this disease process, treatment outcomes are encouraging with the employment of an array of medical and surgical therapies. The goal of this paper is to provide a comprehensive, up to date analysis of the literature concerning the medical management of CRS by highlighting the most recent evidence based recommendations addressing this ongoing field of research. PMID- 26849214 TI - A Lower Olfactory Capacity Is Related to Higher Circulating Concentrations of Endocannabinoid 2-Arachidonoylglycerol and Higher Body Mass Index in Women. AB - The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice. The eCB system is over-active in human obesity. Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system. The study sample was made up of 161 females with five groups of body mass index sub-categories ranging from under weight to morbidly obese. We assessed olfactory capacity with the "Sniffin'Sticks" test, which measures olfactory threshold-discrimination identification (TDI) capacity. We measured plasma concentrations of the eCBs 2 arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine or anandamide (AEA), and several eCB-related compounds, 2-acylglycerols and N-acylethanolamines. 2-AG and other 2-acylglycerols fasting plasma circulating plasma concentrations were higher in obese and morbidly obese subjects. AEA and other N-acylethanolamine circulating concentrations were lower in under-weight subjects. Olfactory TDI scores were lower in obese and morbidly obese subjects. Lower TDI scores were independently associated with higher 2-AG fasting plasma circulating concentrations, higher %body fat, and higher body mass index, after controlling for age, smoking, menstruation, and use of contraceptives. Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity. In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects. PMID- 26849216 TI - Production of Mucosally Transmissible SHIV Challenge Stocks from HIV-1 Circulating Recombinant Form 01_AE env Sequences. AB - Simian-human immunodeficiency virus (SHIV) challenge stocks are critical for preclinical testing of vaccines, antibodies, and other interventions aimed to prevent HIV-1. A major unmet need for the field has been the lack of a SHIV challenge stock expressing circulating recombinant form 01_AE (CRF01_AE) env sequences. We therefore sought to develop mucosally transmissible SHIV challenge stocks containing HIV-1 CRF01_AE env derived from acutely HIV-1 infected individuals from Thailand. SHIV-AE6, SHIV-AE6RM, and SHIV-AE16 contained env sequences that were >99% identical to the original HIV-1 isolate and did not require in vivo passaging. These viruses exhibited CCR5 tropism and displayed a tier 2 neutralization phenotype. These challenge stocks efficiently infected rhesus monkeys by the intrarectal route, replicated to high levels during acute infection, and established chronic viremia in a subset of animals. SHIV-AE16 was titrated for use in single, high dose as well as repetitive, low dose intrarectal challenge studies. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines, monoclonal antibodies, and other interventions targeted at preventing HIV-1 CRF01_AE infection. PMID- 26849217 TI - Comparing Apples and Oranges?: Next Generation Sequencing and Its Impact on Microbiome Analysis. AB - Rapid advancements in sequencing technologies along with falling costs present widespread opportunities for microbiome studies across a vast and diverse array of environments. These impressive technological developments have been accompanied by a considerable growth in the number of methodological variables, including sampling, storage, DNA extraction, primer pairs, sequencing technology, chemistry version, read length, insert size, and analysis pipelines, amongst others. This increase in variability threatens to compromise both the reproducibility and the comparability of studies conducted. Here we perform the first reported study comparing both amplicon and shotgun sequencing for the three leading next-generation sequencing technologies. These were applied to six human stool samples using Illumina HiSeq, MiSeq and Ion PGM shotgun sequencing, as well as amplicon sequencing across two variable 16S rRNA gene regions. Notably, we found that the factor responsible for the greatest variance in microbiota composition was the chosen methodology rather than the natural inter-individual variance, which is commonly one of the most significant drivers in microbiome studies. Amplicon sequencing suffered from this to a large extent, and this issue was particularly apparent when the 16S rRNA V1-V2 region amplicons were sequenced with MiSeq. Somewhat surprisingly, the choice of taxonomic binning software for shotgun sequences proved to be of crucial importance with even greater discriminatory power than sequencing technology and choice of amplicon. Optimal N50 assembly values for the HiSeq was obtained for 10 million reads per sample, whereas the applied MiSeq and PGM sequencing depths proved less sufficient for shotgun sequencing of stool samples. The latter technologies, on the other hand, provide a better basis for functional gene categorisation, possibly due to their longer read lengths. Hence, in addition to highlighting methodological biases, this study demonstrates the risks associated with comparing data generated using different strategies. We also recommend that laboratories with particular interests in certain microbes should optimise their protocols to accurately detect these taxa using different techniques. PMID- 26849220 TI - Letter to the editor (EAPD). PMID- 26849218 TI - Cities through the Prism of People's Spending Behavior. AB - Scientific studies of society increasingly rely on digital traces produced by various aspects of human activity. In this paper, we exploit a relatively unexplored source of data-anonymized records of bank card transactions collected in Spain by a big European bank, and propose a new classification scheme of cities based on the economic behavior of their residents. First, we study how individual spending behavior is qualitatively and quantitatively affected by various factors such as customer's age, gender, and size of his/her home city. We show that, similar to other socioeconomic urban quantities, individual spending activity exhibits a statistically significant superlinear scaling with city size. With respect to the general trends, we quantify the distinctive signature of each city in terms of residents' spending behavior, independently from the effects of scale and demographic heterogeneity. Based on the comparison of city signatures, we build a novel classification of cities across Spain in three categories. That classification exhibits a substantial stability over different city definitions and connects with a meaningful socioeconomic interpretation. Furthermore, it corresponds with the ability of cities to attract foreign visitors, which is a particularly remarkable finding given that the classification was based exclusively on the behavioral patterns of city residents. This highlights the far reaching applicability of the presented classification approach and its ability to discover patterns that go beyond the quantities directly involved in it. PMID- 26849219 TI - Identification of CdnL, a Putative Transcriptional Regulator Involved in Repair and Outgrowth of Heat-Damaged Bacillus cereus Spores. AB - Spores are widely present in the environment and are common contaminants in the food chain, creating a challenge for food industry. Nowadays, heat treatments conventionally applied in food processing may become milder to comply with consumer desire for products with higher sensory and nutritional values. Consequently subpopulations of spores may emerge that are sublethally damaged rather than inactivated. Such spores may germinate, repair damage, and eventually grow out leading to uncontrolled spoilage and safety issues. To gain insight into both the behaviour of damaged Bacillus cereus spores, and the process of damage repair, we assessed the germination and outgrowth performance using OD595 measurements and microscopy combined with genome-wide transcription analysis of untreated and heat-treated spores. The first two methods showed delayed germination and outgrowth of heat-damaged B. cereus ATCC14579 spores. A subset of genes uniquely expressed in heat-treated spores was identified with putative roles in the outgrowth of damaged spores, including cdnL (BC4714) encoding the putative transcriptional regulator CdnL. Next, a B. cereus ATCC14579 cdnL (BC4714) deletion mutant was constructed and assessment of outgrowth from heat treated spores under food relevant conditions showed increased damage compared to wild type spores. The approach used in this study allows for identification of candidate genes involved in spore damage repair. Further identification of cellular parameters and characterisation of the molecular processes contributing to spore damage repair may provide leads for better control of spore outgrowth in foods. PMID- 26849221 TI - Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis. AB - BACKGROUND: Epstein-Barr virus (EBV) infection represents a major environmental risk factor for multiple sclerosis (MS), with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1)-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross reactive immune targets within the central nervous system proteome. METHODS: Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan) and candidates were evaluated for cross recognition with human brain proteins. RESULTS: EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut off). In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes ('AEG': aa 481-496 and 'MVF': aa 562-577), and two putative epitopes between positions 502-543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis. CONCLUSIONS: This study demonstrates the feasibility of obtaining autologous EBNA 1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains. This approach has identified a number of immunogenic regions of EBNA-1 as well as known and novel targets for autoreactive HLA-DRB1*15-restricted T cells within the central nervous system that could arise as a result of cross-reactivity with EBNA-1-specific immune responses. PMID- 26849222 TI - Subcellular Fractionation Analysis of the Extraction of Ubiquitinated Polytopic Membrane Substrate during ER-Associated Degradation. AB - During ER-associated degradation (ERAD), misfolded polytopic membrane proteins are ubiquitinated and retrotranslocated to the cytosol for proteasomal degradation. However, our understanding as to how polytopic membrane proteins are extracted from the ER to the cytosol remains largely unclear. To better define the localization and physical properties of ubiquitinated polytopic membrane substrates in vivo, we performed subcellular fractionation analysis of Ste6*, a twelve transmembrane protein that is ubiquitinated primarily by Doa10 E3 ligase in yeast. Consistent with previous in vitro studies, ubiquitinated Ste6* was extracted from P20 (20,000 g pellet) fraction to S20 (20,000 g supernatant) fraction in a Cdc48/p97-dependent manner. Similarly, Ubx2p, which recruits Cdc48/p97 to the ER, facilitated the extraction of Ste6*. By contrast, lipid droplet formation, which was suggested to be dispensable for the degradation of Hrd1-substrates in yeast, was not required for the degradation of Ste6*. Intriguingly, we found that ubiquitinated Ste6* in the S20 fraction could be enriched by further centrifugation at 100,000 g. Although it is currently uncertain whether ubiquitinated Ste6* in P100 fraction is completely free from any lipids, membrane flotation analysis suggested the existence of two distinct populations of ubiquitinated Ste6* with different states of membrane association. Together, these results imply that ubiquitinated Ste6* may be sequestered into a putative quality control sub-structure by Cdc48/p97. Fractionation assays developed in the present study provide a means to further dissect the ill-defined post-ubiquitination step during ERAD of polytopic membrane substrates. PMID- 26849223 TI - The RNA Domain Vc1 Regulates Downstream Gene Expression in Response to Cyclic Diguanylate in Vibrio cholerae. AB - In many bacterial species, including the aquatic bacterium and human pathogen Vibrio cholerae, the second messenger cyclic diguanylate (c-di-GMP) modulates processes such as biofilm formation, motility, and virulence factor production. By interacting with various effectors, c-di-GMP regulates gene expression or protein function. One type of c-di-GMP receptor is the class I riboswitch, representatives of which have been shown to bind c-di-GMP in vitro. Herein, we examined the in vitro and in vivo function of the putative class I riboswitch in Vibrio cholerae, Vc1, which lies upstream of the gene encoding GbpA, a colonization factor that contributes to attachment of V. cholerae to environmental and host surfaces containing N-acetylglucosamine moieties. We provide evidence that Vc1 RNA interacts directly with c-di-GMP in vitro, and that nucleotides conserved among this class of riboswitch are important for binding. Yet the mutation of these conserved residues individually in the V. cholerae chromosome inconsistently affects the expression of gbpA and production of the GbpA protein. By isolating the regulatory function of Vc1, we show that the Vc1 element positively regulates downstream gene expression in response to c-di-GMP. Together these data suggest that the Vc1 element responds to c-di-GMP in vivo. Positive regulation of gbpA expression by c-di-GMP via Vc1 may influence the ability of V. cholerae to associate with chitin in the aquatic environment and the host intestinal environment. PMID- 26849225 TI - Competitive adsorption of fluoride and natural organic matter onto activated alumina. AB - Natural organic matter (NOM) is a major water constituent that affects the performance of water treatment processes. Several studies have shown that NOM can be adsorbed on the surface of oxides and may compete with other ions. The overall goal of this study was essentially to investigate the competitive adsorption between fluoride and NOM on activated alumina (AA). For this purpose, a humic acid (HA) was used as a model compound for NOM. The interaction of NOM with fluoride, the simultaneous competitive adsorption, and the effect of preloading AA with NOM were investigated. The specific absorbance of HA was determined at 254 nm. Size-exclusion chromatography measurements confirmed the adsorption of aromatic fractions of NOM onto AA. The presence of HA in the system inhibited fluoride sorption onto AA and the removal yield using fresh AA decreased from 70.4 % to 51.0 % in the presence of HA. The decrease was more pronounced using AA preloaded with HA, reaching 37.7 %. The interference of coexisting ions and their effect on fluoride removal capacity were evaluated, showing a severe impact of the presence of phosphate on the removal capacity unlike nitrates and sulfates, which slightly improved the fluoride sorption. PMID- 26849224 TI - Contralateral Noise Stimulation Delays P300 Latency in School-Aged Children. AB - BACKGROUND AND OBJECTIVE: The auditory cortex modulates auditory afferents through the olivocochlear system, which innervates the outer hair cells and the afferent neurons under the inner hair cells in the cochlea. Most of the studies that investigated the efferent activity in humans focused on evaluating the suppression of the otoacoustic emissions by stimulating the contralateral ear with noise, which assesses the activation of the medial olivocochlear bundle. The neurophysiology and the mechanisms involving efferent activity on higher regions of the auditory pathway, however, are still unknown. Also, the lack of studies investigating the effects of noise on human auditory cortex, especially in peadiatric population, points to the need for recording the late auditory potentials in noise conditions. Assessing the auditory efferents in schoolaged children is highly important due to some of its attributed functions such as selective attention and signal detection in noise, which are important abilities related to the development of language and academic skills. For this reason, the aim of the present study was to evaluate the effects of noise on P300 responses of children with normal hearing. METHODS: P300 was recorded in 27 children aged from 8 to 14 years with normal hearing in two conditions: with and whitout contralateral white noise stimulation. RESULTS: P300 latencies were significantly longer at the presence of contralateral noise. No significant changes were observed for the amplitude values. CONCLUSION: Contralateral white noise stimulation delayed P300 latency in a group of school-aged children with normal hearing. These results suggest a possible influence of the medial olivocochlear activation on P300 responses under noise condition. PMID- 26849226 TI - Distinctive Architecture of the Chloroplast Genome in the Chlorodendrophycean Green Algae Scherffelia dubia and Tetraselmis sp. CCMP 881. AB - The Chlorodendrophyceae is a small class of green algae belonging to the core Chlorophyta, an assemblage that also comprises the Pedinophyceae, Trebouxiophyceae, Ulvophyceae and Chlorophyceae. Here we describe for the first time the chloroplast genomes of chlorodendrophycean algae (Scherffelia dubia, 137,161 bp; Tetraselmis sp. CCMP 881, 100,264 bp). Characterized by a very small single-copy (SSC) region devoid of any gene and an unusually large inverted repeat (IR), the quadripartite structures of the Scherffelia and Tetraselmis genomes are unique among all core chlorophytes examined thus far. The lack of genes in the SSC region is offset by the rich and atypical gene complement of the IR, which includes genes from the SSC and large single-copy regions of prasinophyte and streptophyte chloroplast genomes having retained an ancestral quadripartite structure. Remarkably, seven of the atypical IR-encoded genes have also been observed in the IRs of pedinophycean and trebouxiophycean chloroplast genomes, suggesting that they were already present in the IR of the common ancestor of all core chlorophytes. Considering that the relationships among the main lineages of the core Chlorophyta are still unresolved, we evaluated the impact of including the Chlorodendrophyceae in chloroplast phylogenomic analyses. The trees we inferred using data sets of 79 and 108 genes from 71 chlorophytes indicate that the Chlorodendrophyceae is a deep-diverging lineage of the core Chlorophyta, although the placement of this class relative to the Pedinophyceae remains ambiguous. Interestingly, some of our phylogenomic trees together with our comparative analysis of gene order data support the monophyly of the Trebouxiophyceae, thus offering further evidence that the previously observed affiliation between the Chlorellales and Pedinophyceae is the result of systematic errors in phylogenetic reconstruction. PMID- 26849227 TI - Anti-Inflammatory Effects of beta2-Receptor Agonists Salbutamol and Terbutaline Are Mediated by MKP-1. AB - Mitogen-activated protein kinase phosphatase 1 (MKP-1) expression is induced by inflammatory factors, and it is an endogenous suppressor of inflammatory response. MKP-1 expression is increased by PDE4 inhibitor rolipram suggesting that it is regulated by cAMP-enhancing compounds. Therefore, we investigated the effect of beta2-receptor agonists on MKP-1 expression and inflammatory response. We found that beta2-receptor agonists salbutamol and terbutaline, as well as 8-Br cAMP, increased MKP-1 expression. Salbutamol and terbutaline also inhibited p38 MAPK phosphorylation and TNF production in J774 mouse macrophages. Interestingly, salbutamol suppressed carrageenan-induced paw inflammation in wild-type mice, but the effect was attenuated in MKP-1(-/-) mice. In conclusion, these data show that beta2-receptor agonists increase MKP-1 expression, which seems to mediate, at least partly, the observed anti-inflammatory effects of beta2-receptor agonists. PMID- 26849229 TI - gamma-Lactam alkaloids from the flower buds of daylily. AB - Four new alkaloids, hemerocallisamines IV-VII, were isolated from the methanol extract of flower buds of daylily. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. The absolute stereochemistry of the hemerocallisamines IV-VI was elucidated by the application of the modified Mosher's method, HPLC analysis, and optical rotation. In the present study, the isolated alkaloids significantly inhibited the aggregation of Abeta42 in vitro. This is the first report about bioactive alkaloids with a gamma-lactam ring from daylily. In addition, isolated nucleosides showed accelerative effects on neurite outgrowth under the non fasting condition. PMID- 26849230 TI - Protective Effects of Myrtol Standardized Against Radiation-Induced Lung Injury. AB - BACKGROUND/AIMS: As a major complication after thoracic radiotherapy, radiation induced lung injury (RILI) has great impact on long term quality of life and could result in fatal respiratory insufficiency The present study was aimed to evaluate the effects of Myrtol standardized on RILI, and to investigate the underlying mechanism. METHODS: A mouse model of radiation-induced lung injury was generated by using thoracic irradiation with a single dose of 16Gy. Mice were orally administrated with Myrtol (25 mg/kg/day) for 4 weeks after irradiation, while prednisone (5 mg/kg/day) was used as a positive control. After then, the body weight and lung coefficient were calculated. The severity of fibrosis was evaluated by observing pulmonary sections after radiation and collagen content in lung tissues was calculated following the hydroxyproline (HYP) assay. Pathological changes were observed in all the groups by using HE staining and Masson staining. The serum levels of TGF-beta1, TNF-alpha, IL-1beta, IL-6, and PGE2 were also measured with an ELISA assay. Western blot assay was used to measure the impact of Myrtol on AKT and its downstream signaling pathway, including MMP-2 and MMP-9. The levels of Vimentin and alpha-SMA were evaluated with an immunofluorescence assay. RESULTS: Treatment with Myrtol standardized, but not prednisone, reduced lung coefficient and collagen deposition in lung tissues, while attenuated histological damages induced by irradiation. Myrtol standardized also reduced the production of MDA, while increased the level of SOD. It was also observed that Myrtol standardized inhibited TGF-beta1 and a series of pro-inflammatory cytokines including TNF-alpha, IL-1beta, IL-6, PGE2. While in prednisone group, even though the early pneumonitis was ameliorated, the collagen disposition remained unchanged in latter times. Immunofluorescence analysis also revealed elevation of vimentin and alpha-SMA in the alveoli after a single dose of 16Gy. CONCLUSION: The present results suggest Myrtol standardized as an effective agent for attenuating the lung injury induced by irradiation. PMID- 26849228 TI - The Burden of Provider-Initiated Preterm Birth and Associated Factors: Evidence from the Brazilian Multicenter Study on Preterm Birth (EMIP). AB - BACKGROUND: About 15 million children are born under 37 weeks of gestation worldwide. Prematurity is the leading cause of neonatal deaths and short/long term morbidities, entailing consequences not only for the individual, but also their family, health agencies, facilities and all community. The provider initiated preterm birth is currently one of the most important obstetric conditions related to preterm births, particularly in middle and high income countries, thus decreasing the need for therapeutic preterm birth is essential to reduce global prematurity. Therefore detailed knowledge on the factors associated with provider-initiated preterm birth is essential for the efforts to reduce preterm birth rates and its consequences. In this current analysis we aimed to assess the proportion of provider-initiated (pi-PTB) among preterm births in Brazil and identify associated factors. METHODS AND FINDINGS: This is an analysis of a multicenter cross-sectional study with a nested case-control component called Brazilian Multicenter Study on Preterm Birth (EMIP). EMIP was conducted in 20 referral obstetric hospitals located in the three most populated of the five Brazilian regions. We analysed data of women with pi-PTB, defined as childbirth occurring at less than 37 weeks, medically indicated for maternal/fetal compromise or both; and women with term birth, childbirth at or after 37 weeks. Maternal, sociodemographic, obstetric, prenatal care, delivery, and postnatal characteristics were assessed as possible factors associated with pi-PTB, compared to term births. The overall prevalence of preterm births was 12.3%. Of these, approximately one-third of cases were initiated by the provider. Hypertensive disorders, placental abruption, and diabetes were the main maternal conditions leading to pi-PTB. Caesarean section was the most common mode of delivery. Chronic hypertension (OR 7.47; 95%CI 4.02-13.88), preeclampsia/eclampsia/HELLP syndrome (OR 15.35; 6.57-35.88), multiple pregnancy (OR 12.49; 4.86-32.05), and chronic diabetes (OR 5.24; 2.68-10.25) were the most significant factors independently associated with pi-PTB. CONCLUSIONS: pi-PTB is responsible for about one-third of all preterm births, requiring special attention. The decision-making process relative to the choice of provider initiated birth is complex, and many factors should be elucidated to improve strategies for its prevention, including evidence-based guidelines on proper management of the corresponding clinical conditions. PMID- 26849231 TI - Epidemiologic Study of Charcot-Marie-Tooth Disease: A Systematic Review. AB - BACKGROUND: Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy. CMT is classified into 2 main subgroups: CMT type 1 (CMT1; demyelinating form) and CMT type 2 (CMT2; axonal form). The objectives of this study were to systematically review and assess the quality of studies reporting the incidence and/or prevalence of CMT worldwide. SUMMARY: A total of 802 studies were initially identified, with only 12 meeting the inclusion criteria. CMT prevalence was reported in 10 studies and ranged from 9.7/100,000 in Serbia to 82.3/100,000 in Norway. The frequency of the main subtypes varied from 37.6 to 84% for CMT1 and from 12 to 35.9% for CMT2; the country with the lowest prevalence of CMT1 was Norway, and the country with the highest prevalence of CMT1 was Iceland; on the other hand, CMT2 was least prevalent in the United Kingdom and most prevalent in Norway. KEY MESSAGES: This review reveals the gaps that still exist in the epidemiological knowledge of CMT around the world. Published studies are of varying quality and utilise different methodologies, thus precluding a robust conclusion. Additional research focusing on epidemiological features of CMT in different nations and different ethnic groups is needed. PMID- 26849232 TI - Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is involved in cervical cancer stemness and can be a target of immunotherapy. AB - Cervical cancer is a major cause of cancer death in females worldwide. Cervical cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are resistant to conventional radiotherapy and chemotherapy, and CSCs/CICs are thought to be responsible for recurrence. Eradication of CSCs/CICs is thus essential to cure cervical cancer. In this study, we isolated cervical CSCs/CICs by sphere culture, and we identified a cancer testis (CT) antigen, CTCFL/BORIS, that is expressed in cervical CSCs/CICs. BORIS has 23 mRNA isoform variants classified by 6 subfamilies (sfs), and they encode 17 different BORIS peptides. BORIS sf1 and sf4 are expressed in both CSCs/CICs and non-CSCs/CICs, whereas BORIS sf6 is expressed only in CSCs/CICs. Overexpression of BORIS sf6 in cervical cancer cells increased sphere formation and tumor-initiating ability compared with those in control cells, whereas overexpression of BORIS sf1 and BORIS sf4 resulted in only slight increases. Thus, BORIS sf6 is a cervical CSC/CIC-specific subfamily and has a role in the maintenance of cervical CSCs/CICs. BORIS sf6 contains a specific c terminal domain (C34), and we identified a human leukocyte antigen (HLA)-A2 restricted antigenic peptide, BORIS C34_24(9) encoded by BORIS sf6. A BORIS C34_24(9)-specific cytotoxic T cell (CTL) clone showed cytotoxicity for BORIS sf6 overexpressing cervical cancer cells. Furthermore, the CTL clone significantly suppressed sphere formation of CaSki cells. Taken together, the results indicate that the CT antigen BORIS sf6 is specifically expressed in cervical CSCs/CICs, that BORIS sf6 has a role in the maintenance of CSCs/CICs, and that BORIS C34_24(9) peptide is a promising candidate for cervical CSC/CIC-targeting immunotherapy. PMID- 26849233 TI - HIF2alpha contributes to antiestrogen resistance via positive bilateral crosstalk with EGFR in breast cancer cells. AB - The majority of breast cancers express estrogen receptor alpha (ERalpha), and most patients with ERalpha-positive breast cancer benefit from antiestrogen therapy. The ERalpha-modulator tamoxifen and ERalpha-downregulator fulvestrant are commonly employed antiestrogens. Antiestrogen resistance remains a clinical challenge, with few effective treatments available for patients with antiestrogen resistant breast cancer. Hypoxia, which is intrinsic to most tumors, promotes aggressive disease, with the hypoxia-inducible transcription factors HIF1 and HIF2 regulating cellular responses to hypoxia. Here, we show that the ERalpha expressing breast cancer cells MCF-7, CAMA-1, and T47D are less sensitive to antiestrogens when hypoxic. Furthermore, protein and mRNA levels of HIF2alpha/HIF2A were increased in a panel of antiestrogen-resistant cells, and antiestrogen-exposure further increased HIF2alpha expression. Ectopic expression of HIF2alpha in MCF-7 cells significantly decreased sensitivity to antiestrogens, further implicating HIF2alpha in antiestrogen resistance. EGFR is known to contribute to antiestrogen resistance: we further show that HIF2alpha drives hypoxic induction of EGFR and that EGFR induces HIF2alpha expression. Downregulation or inhibition of EGFR led to decreased HIF2alpha levels. This positive and bilateral HIF2-EGFR regulatory crosstalk promotes antiestrogen resistance and, where intrinsic hypoxic resistance exists, therapy itself may exacerbate the problem. Finally, inhibition of HIFs by FM19G11 restores antiestrogen sensitivity in resistant cells. Targeting HIF2 may be useful for counteracting antiestrogen resistance in the clinic. PMID- 26849234 TI - NMU signaling promotes endometrial cancer cell progression by modulating adhesion signaling. AB - Neuromedin U (NMU) was originally named based on its strong uterine contractile activity, but little is known regarding its signaling/functions in utero. We identified that NMU and one of its receptors, NMUR2, are not only present in normal uterine endometrium but also co-expressed in endometrial cancer tissues, where the NMU level is correlated with the malignant grades and survival of patients. Cell-based assays further confirmed that NMU signaling can promote cell motility and proliferation of endometrial cancer cells derived from grade II tumors. Activation of NMU pathway in these endometrial cancer cells is required in order to sustain expression of various adhesion molecules, such as CD44 and integrin alpha1, as well as production of their corresponding extracellular matrix ligands, hyaluronan and collagen IV; it also increased the activity of SRC and its downstream proteins RHOA and RAC1. Thus, it is concluded that NMU pathway positively controls the adhesion signaling-SRC-Rho GTPase axis in the tested endometrial cancer cells and that changes in cell motility and proliferation can occur when there is manipulation of NMU signaling in these cells either in vitro or in vivo. Intriguingly, this novel mechanism also explains how NMU signaling promotes the EGFR-driven and TGFbeta receptor-driven mesenchymal transitions. Through the above axis, NMU signaling not only can promote malignancy of the tested endometrial cancer cells directly, but also helps these cells to become more sensitive to niche growth factors in their microenvironment. PMID- 26849236 TI - Genetic mapping with an inbred line-derived F2 population in potato. AB - KEY MESSAGE: This is the first report of the production and use of a diploid inbred line-based F2 population for genetic mapping in potato. Potato (Solanum tuberosum L.) is an important global food crop, for which tetrasomic inheritance and self-incompatibility have limited both genetic discovery and breeding gains. We report here on the creation of the first diploid inbred line-derived F2 population in potato, and demonstrate its utility for genetic mapping. To create the population, the doubled monoploid potato DM1-3 was crossed as a female to M6, an S7 inbred line derived from the wild relative S. chacoense, and a single F1 plant was then self-pollinated. A genetic linkage map with 2264 single nucleotide polymorphisms was constructed and used to improve the physical anchoring of superscaffolds in the potato reference genome, which is based on DM1-3. Segregation was observed for skin and flesh color, skin and flesh pigment intensity, tuber shape, anther development, jelly end, and the presence of eye tubers instead of normal sprouts. Using the R/qtl software, we detected 10 genes, 7 of which have been previously mapped and 3 for which this is the first publication. The latter category includes tightly linked genes for the jelly end and eye tuber traits on chromosome 5. The development of recombinant inbred lines from this F2 population by single-seed descent is underway and should facilitate even better resolution of these and other loci. PMID- 26849235 TI - Heparanase promotes myeloma progression by inducing mesenchymal features and motility of myeloma cells. AB - Bone dissemination and bone disease occur in approximately 80% of patients with multiple myeloma (MM) and are a major cause of patient mortality. We previously demonstrated that MM cell-derived heparanase (HPSE) is a major driver of MM dissemination to and progression in new bone sites. However the mechanism(s) by which HPSE promotes MM progression remains unclear. In the present study, we investigated the involvement of mesenchymal features in HPSE-promoted MM progression in bone. Using a combination of molecular, biochemical, cellular, and in vivo approaches, we demonstrated that (1) HPSE enhanced the expression of mesenchymal markers in both MM and vascular endothelial cells; (2) HPSE expression in patient myeloma cells positively correlated with the expression of the mesenchymal markers vimentin and fibronectin. Additional mechanistic studies revealed that the enhanced mesenchymal-like phenotype induced by HPSE in MM cells is due, at least in part, to the stimulation of the ERK signaling pathway. Finally, knockdown of vimentin in HPSE expressing MM cells resulted in significantly attenuated MM cell dissemination and tumor growth in vivo. Collectively, these data demonstrate that the mesenchymal features induced by HPSE in MM cells contribute to enhanced tumor cell motility and bone dissemination. PMID- 26849237 TI - A remorin gene is implicated in quantitative disease resistance in maize. AB - KEY MESSAGE: Quantitative disease resistance is used by plant breeders to improve host resistance. We demonstrate a role for a maize remorin ( ZmREM6.3 ) in quantitative resistance against northern leaf blight using high-resolution fine mapping, expression analysis, and mutants. This is the first evidence of a role for remorins in plant-fungal interactions. Quantitative disease resistance (QDR) is important for the development of crop cultivars and is particularly useful when loci also confer multiple disease resistance. Despite its widespread use, the underlying mechanisms of QDR remain largely unknown. In this study, we fine mapped a known quantitative trait locus (QTL) conditioning disease resistance on chromosome 1 of maize. This locus confers resistance to three foliar diseases: northern leaf blight (NLB), caused by the fungus Setosphaeria turcica; Stewart's wilt, caused by the bacterium Pantoea stewartii; and common rust, caused by the fungus Puccinia sorghi. The Stewart's wilt QTL was confined to a 5.26-Mb interval, while the rust QTL was reduced to an overlapping 2.56-Mb region. We show tight linkage between the NLB QTL locus and the loci conferring resistance to Stewart's wilt and common rust. Pleiotropy cannot be excluded for the Stewart's wilt and the common rust QTL, as they were fine-mapped to overlapping regions. Four positional candidate genes within the 243-kb NLB interval were examined with expression and mutant analysis: a gene with homology to an F-box gene, a remorin gene (ZmREM6.3), a chaperonin gene, and an uncharacterized gene. The F-box gene and ZmREM6.3 were more highly expressed in the resistant line. Transposon tagging mutants were tested for the chaperonin and ZmREM6.3, and the remorin mutant was found to be more susceptible to NLB. The putative F-box is a strong candidate, but mutants were not available to test this gene. Multiple lines of evidence strongly suggest a role for ZmREM6.3 in quantitative disease resistance. PMID- 26849238 TI - Resynthesis of Brassica napus through hybridization between B. juncea and B. carinata. AB - KEY MESSAGE: First report for the resynthesis of Brassica napus by recombining A and C genome from B. juncea and B. carinata , respectively. Also documents B genome introgressions in resynthesized B. napus. Resynthesis of Brassica napus (AACC) was achieved by hybridizing Brassica juncea (AABB) with Brassica carinata (BBCC). This was facilitated by spontaneous chromosome doubling in the F1 hybrid (ABBC) to yield octaploid (AABBBBCC), elimination of extra B genome chromosomes in the resulting octaploid and in subsequent selfed generations, aided with directed selection for fertile plants having B. napus morphology. Twenty-five plants with varying degrees of resemblance to natural B. napus were identified from 17 A5 progenies and assayed for cytogenetic stability and genetic diversity. Majority of these plants, except six (2n = 38) were hyperploids (2n = 40-56). The six plants with 2n = 38 were designated as derived B. napus types. These showed an expected meiotic configuration of 19II at metaphase-I, with 19-19 distribution at anaphase-I. Genotyping based on A and C genome specific primers confirmed genetic identity of six derived (2n = 38) B. napus plants with natural types whereas genotyping with B genome specific primers indicated introgression of B genome segments. This was also confirmed by genomic in situ hybridization (GISH). Strong signals of B genome probe were detected, proving hitherto unreported genetic exchanges between B and A/C chromosomes. These introgressions possibly occurred en route five generations of selfing. Derived plants yielded fertile hybrids in crosses with natural B. napus var. GSC 6. The selfed derived plants as evaluated in A6 plant to progeny rows were morphologically similar to natural B. napus, and meiotically stable. Agronomic assessment of these progenies revealed variation for key morpho-physiological traits. Of special interest were the progenies with plants having oil content exceeding 47% as against about 39-41% in existing cultivars. PMID- 26849240 TI - Silver-Mediated Trifluoromethylthiolation-Iodination of Arynes. AB - A one-pot trifluoromethylthiolation-iodination of arynes with trifluoromethylthiosilver (AgSCF3) and 1-iodophenylacetylene is described. This protocol allows rapid construction of o-trifluoromethylthiolated arene building blocks in moderate yields. These products were found to be excellent precursors for Yagupolskii-Umemoto-type electrophilic trifluoromethylation reagents. PMID- 26849239 TI - Molecular characterization of CIMMYT maize inbred lines with genotyping-by sequencing SNPs. AB - KEY MESSAGE: Molecular characterization information on genetic diversity, population structure and genetic relationships provided by this research will help maize breeders to better understand how to utilize the current CML collection. CIMMYT maize inbred lines (CMLs) have been widely used all over the world and have contributed greatly to both tropical and temperate maize improvement. Genetic diversity and population structure of the current CML collection and of six temperate inbred lines were assessed and relationships among all lines were determined with genotyping-by-sequencing SNPs. Results indicated that: (1) wider genetic distance and low kinship coefficients among most pairs of lines reflected the uniqueness of most lines in the current CML collection; (2) the population structure and genetic divergence between the Temperate subgroup and Tropical subgroups were clear; three major environmental adaptation groups (Lowland Tropical, Subtropical/Mid-altitude and Highland Tropical subgroups) were clearly present in the current CML collection; (3) the genetic diversity of the three Tropical subgroups was similar and greater than that of the Temperate subgroup; the average genetic distance between the Temperate and Tropical subgroups was greater than among Tropical subgroups; and (4) heterotic patterns in each environmental adaptation group estimated using GBS SNPs were only partially consistent with patterns estimated based on combining ability tests and pedigree information. Combining current heterotic information based on combining ability tests and the genetic relationships inferred from molecular marker analyses may be the best strategy to define heterotic groups for future tropical maize improvement. Information resulting from this research will help breeders to better understand how to utilize all the CMLs to select parental lines, replace testers, assign heterotic groups and create a core set of breeding germplasm. PMID- 26849241 TI - Rebamipide retards CCl4-induced hepatic fibrosis in rats: Possible role for PGE2. AB - Prostaglandin E2 (PGE2) is a potent physiological suppressor of liver fibrosis. Because the anti-ulcer drug rebamipide can induce the formation of endogenous PGE2, this study investigated the potential effects of rebamipide on development of a hepatic fibrosis that was inducible by carbon tetrachloride (CCl4). Groups of Wistar rats received intraperitoneal (IP) injections of CCl4 (0.45 ml/kg [0.72 g CCl4/kg]) over the course of for 4 weeks. Sub-sets of CCl4-treated rats were also treated concurrently with rebamipide at 60 or 100 mg/kg. At 24 h after the final treatments, liver function and oxidative stress were indirectly assessed. The extent of hepatic fibrosis was evaluated using two fibrotic markers, hyaluronic acid (HA) and pro-collagen-III (Procol-III); isolated liver tissues underwent histology and were evaluated for interleukin (IL)-10 and PGE2 content. The results indicated that treatment with rebamipide significantly inhibited CCl4 induced increases in serum ALT and AST and also reduced oxidative stress induced by CCl4. Fibrotic marker assays revealed that either dose of rebamipide decreased the host levels of Procol-III and HA that had become elevated due to the CCl4. At the higher dose tested, rebamipide appeared to be able to permit the hosts to have a normal liver histology and to minimize any CCl4-induced collagen precipitation in the liver. Lastly, the use of rebamipide was seen to be associated with significant increases in liver levels of both PGE2 and the anti inflammatory cytokine IL-10. Based on these findings, it is concluded that rebamipide can retard hepatic fibrosis induced by CCl4 and that this effect may, in part, be mediated by an induction of PGE2 and IL-10 in the liver itself. PMID- 26849242 TI - Cathodoluminescence and Electron-Induced Fluorescence Enhancement of Enhanced Green Fluorescent Protein. AB - Becaues the spatial resolution of fluorescence microscopy is not high enough to study the molecular level of relationship between the structure and function of biological specimens, correlative light and electron microscopy has been used for this purpose. Another possibility for a high-resolution light microscopy is cathodoluminescence microscopy. Here, we report a new phenomenon, the electron induced activation of luminescence (cathodoluminescence) and electron-enhanced fluorescence for the enhanced green fluorescent protein (EGFP). This was found using our recently developed hybrid fluorescence and electron microscopy. Contrary to the past reports, which showed a degradation of organic compounds by electron irradiation, stable cathodoluminescence emitted from an organic molecule, EGFP, has been observed using the hybrid microscopy. Addition of the glycerol promoted the fluorescence enhancement of EGFP probably due to the change in the electronic state density of excitation channels from the ground to the excited state or of relaxation channels from the excited to the emission state. Stable cathodoluminescence and enhanced fluorescence of the EGFP may introduce a cathodoluminescence microscopy, which will increase the variety of the imaging to investigate the biological compounds. PMID- 26849243 TI - Long-Term Macular Changes in the First Proband of Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC) Due to a Newly Identified Mutation in BEST1. AB - BACKGROUND: Mutations in BEST1 account for autosomal dominant vitreoretinochoroidopathy (ADVIRC), a rare inherited retinal dystrophy with presenile cataracts and incomplete anterior segment development. The long-term clinical findings and visual prognosis of these patients continues to evolve over time. MATERIALS AND METHODS: The retina was assessed by fundus photography, fluorescein angiography, and spectral domain optical coherence tomography. Sanger dideoxy chain-termination sequencing identified mutations in BEST1. Bioinformatic tools were used to predict changes in splicing. An in vitro splicing assay was applied to evaluate for altered pre-mRNA splicing. RESULTS: Long-term follow up of the first ever reported ADVIRC proband revealed progressive foveal atrophy in both eyes 3 decades after his initial presentation. Progressive retinal ischemia, bilateral iris atrophy, and pseudophakodnesis were observed on follow up. The patient was heterozygous for a c.248G > A missense mutation in exon 4 of BEST1, affecting a highly conserved transmembrane domain. Although computational prediction models suggest a change in the binding probability of splicing associated SR proteins, in vitro splicing assays failed to demonstrate an effect of the c.248G > A mutation on splicing of BEST1 exon 3 or exon 4. CONCLUSIONS: Progressive posterior chorioretinal changes occurred over time in the initial ADVIRC proband, leading to visual loss. The causative mutation in this patient falls in the transmembrane domain of the BEST1 protein, with unclear functional consequences. Although previous studies showed alteration in pre-mRNA splicing, in vitro splicing assays failed to demonstrate this in our patient. PMID- 26849244 TI - Spread of bacterial genomes in packaged particles. PMID- 26849245 TI - Anatomical location of the vocal cords in relation to cervical vertebrae: A new predictor of difficult laryngoscopy? AB - BACKGROUND: Several anatomical factors, such as prognathism, sex, short thyromental distance and others are known to make direct laryngoscopy difficult. OBJECTIVE: We investigated the hypothesis that the anatomical position of the vocal cords in relation to the cervical vertebrae correlates with difficult laryngoscopy. Existing MRI was used to identify the position of the vocal cords relative to the cervical spine in patients with and without difficult laryngoscopy. DESIGN: Observational study with adaptive enrichment. SETTING: University hospital. PATIENTS: A total of 142 adult patients, 91 with easy (Cormack-Lehane class 1 or 2) and 51 with difficult (Cormack-Lehane class 3 or 4) laryngoscopy. MAIN OUTCOME MEASURES: Position of the vocal cords relative to cervical vertebrae in patients with easy vs. difficult laryngoscopy. RESULTS: In patients with difficult laryngoscopy, we found a higher incidence of cranial position of the vocal cords in relation to the cervical spine compared with patients with easy laryngoscopy (P < 0.001). CONCLUSION: Anaesthesiologists should take advantage of existing imaging of the cervical spine when assessing the patient's airway. PMID- 26849246 TI - The impact of primary care organization on avoidable hospital admissions for diabetes in 23 countries. AB - OBJECTIVE: Diabetes is a so-called ambulatory care sensitive condition. It is assumed that by appropriate and timely primary care, hospital admissions for complications of such conditions can be avoided. This study examines whether differences between countries in diabetes-related hospitalization rates can be attributed to differences in the organization of primary care in these countries. DESIGN: Data on characteristics of primary care systems were obtained from the QUALICOPC study that includes surveys held among general practitioners and their patients in 34 countries. Data on avoidable hospitalizations were obtained from the OECD Health Care Quality Indicator project. Negative binomial regressions were carried out to investigate the association between characteristics of primary care and diabetes-related hospitalizations. SETTING: A total of 23 countries. SUBJECTS: General practitioners and patients. MAIN OUTCOME MEASURES: Diabetes-related avoidable hospitalizations. RESULTS: Continuity of care was associated with lower rates of diabetes-related hospitalization. Broader task profiles for general practitioners and more medical equipment in general practice were associated with higher rates of admissions for uncontrolled diabetes. Countries where patients perceive better access to care had higher rates of hospital admissions for long-term diabetes complications. There was no association between disease management programmes and rates of diabetes-related hospitalization. Hospital bed supply was strongly associated with admission rates for uncontrolled diabetes and long-term complications. CONCLUSIONS: Countries with elements of strong primary care do not necessarily have lower rates of diabetes-related hospitalizations. Hospital bed supply appeared to be a very important factor in this relationship. Apparently, it takes more than strong primary care to avoid hospitalizations. KEY POINTS: Countries with elements of strong primary care do not necessarily have lower rates of diabetes-related avoidable hospitalization. Hospital bed supply is strongly associated with admission rates for uncontrolled diabetes and long-term complications. Continuity of care was associated with lower rates of diabetes-related hospitalization. Better access to care, broader task profiles for general practitioners, and more medical equipment in general practice was associated with higher rates of admissions for diabetes. PMID- 26849247 TI - Using Automatic Item Generation to Improve the Quality of MCQ Distractors. AB - CONSTRUCT: Automatic item generation (AIG) is an alternative method for producing large numbers of test items that integrate cognitive modeling with computer technology to systematically generate multiple-choice questions (MCQs). The purpose of our study is to describe and validate a method of generating plausible but incorrect distractors. Initial applications of AIG demonstrated its effectiveness in producing test items. However, expert review of the initial items identified a key limitation where the generation of implausible incorrect options, or distractors, might limit the applicability of items in real testing situations. BACKGROUND: Medical educators require development of test items in large quantities to facilitate the continual assessment of student knowledge. Traditional item development processes are time-consuming and resource intensive. Studies have validated the quality of generated items through content expert review. However, no study has yet documented how generated items perform in a test administration. Moreover, no study has yet to validate AIG through student responses to generated test items. APPROACH: To validate our refined AIG method in generating plausible distractors, we collected psychometric evidence from a field test of the generated test items. A three-step process was used to generate test items in the area of jaundice. At least 455 Canadian and international medical graduates responded to each of the 13 generated items embedded in a high stake exam administration. Item difficulty, discrimination, and index of discrimination estimates were calculated for the correct option as well as each distractor. RESULTS: Item analysis results for the correct options suggest that the generated items measured candidate performances across a range of ability levels while providing a consistent level of discrimination for each item. Results for the distractors reveal that the generated items differentiated the low- from the high-performing candidates. CONCLUSIONS: Previous research on AIG highlighted how this item development method can be used to produce high-quality stems and correct options for MCQ exams. The purpose of the current study was to describe, illustrate, and evaluate a method for modeling plausible but incorrect options. Evidence provided in this study demonstrates that AIG can produce psychometrically sound test items. More important, by adapting the distractors to match the unique features presented in the stem and correct option, the generation of MCQs using automated procedure has the potential to produce plausible distractors and yield large numbers of high-quality items for medical education. PMID- 26849248 TI - Reply to specific gene patterns and molecular pathways related to human carcinogenesis in different populations among various geographic locations. PMID- 26849250 TI - Stress ulcer prophylaxis in the intensive care unit. AB - PURPOSE OF REVIEW: Stress ulcer prophylaxis (SUP) is considered standard of care in the majority of critically ill patients in the ICU. In this review, we will present the current evidence for the use of SUP in ICU patients, including data on the prevalence of gastrointestinal bleeding and the balance between benefits and harms of SUP. RECENT FINDINGS: The prevalence of overt gastrointestinal bleeding in critically ill patients is in the area of 5%. Consistent risk factors for gastrointestinal bleeding have been identified, but indications for SUP vary considerably. SUP is used in three out of four critically ill patients, most frequently in the form of proton pump inhibitors. A recent systematic review of SUP vs. placebo or no prophylaxis in critically ill patients highlights the lack of evidence supporting the use of SUP. Importantly, data suggest potential harm, including increased risk of nosocomial infections and cardiovascular events. SUMMARY: The prevalence of gastrointestinal bleeding in critically ill patients in the ICU is low, the prognostic importance is ambiguous, and SUP is widely used. The balance between benefits and harms of SUP is unknown, and clinical equipoise exists. High-quality randomized controlled trials and systematic reviews assessing benefits and harms of SUP in ICU patients are highly warranted. PMID- 26849249 TI - Helical Growth of Ultrathin Gold-Copper Nanowires. AB - In this work, we report the synthesis and detailed structural characterization of novel helical gold-copper nanowires. The nanowires possess the Boerdijk-Coxeter Bernal structure, based on the pile up of octahedral, icosahedral, and/or decahedral seeds. They are self-assembled into a coiled manner as individual wires or into a parallel-ordering way as groups of wires. The helical nanowires are ultrathin with a diameter of less than 10 nm and variable length of several micrometers, presenting a high density of twin boundaries and stacking faults. To the best of our knowledge, such gold-copper nanowires have never been reported previously. PMID- 26849251 TI - Emerging strategies for the treatment of patients with acute hepatic failure. AB - PURPOSE OF REVIEW: The objective of this article is to review the latest developments related to the treatment of patients with acute liver failure (ALF). RECENT FINDINGS: As the treatment of ALF has evolved, there is an increasing recognition regarding the risk of intracranial hypertension related to advanced hepatic encephalopathy. Therefore, there is an enhanced emphasis on neuromonitoring and therapies targeting intracranial hypertension. Also, new evidence implicates systemic proinflammatory cytokines as an etiology for the development of multiorgan system dysfunction in ALF; the recent finding of a survival benefit in ALF with high-volume plasmapheresis further supports this theory. SUMMARY: Advances in the critical care management of ALF have translated to a substantial decrease in mortality related to this disease process. The extrapolation of therapies from general neurocritical care to the treatment of ALF-induced intracranial hypertension has resulted in improved neurologic outcomes. In addition, recognition of the systemic inflammatory response and multiorgan dysfunction in ALF has guided current treatment recommendations, and will provide avenues for future research endeavors. With respect to extracorporeal liver support systems, further randomized studies are required to assess their efficacy in ALF, with attention to nonsurvival end points such as bridging to liver transplantation. PMID- 26849252 TI - Molecular Characterization of Pro-Inflammatory Cytokines Interleukin-1beta and Interleukin-8 in Asian Elephant (Elephas maximus). AB - Interleukin (IL)-1beta and IL-8 are pro-inflammatory cytokines produced primarily by monocytes and macrophages in response to a variety of microbial and nonmicrobial agents. As yet, no molecular data have been reported for IL-1beta and IL-8 of the Asian elephant. In the present study, we have cloned and sequenced the cDNA encoding IL-1beta and IL-8 of the Asian elephant. The open reading frame (ORF) of Asian elephant IL-1beta is 789 bp in length, encoded a propeptide of 263 amino acid polypeptide. The predicted protein revealed the presence of IL-1 family signature motif and an ICE cut site. Whereas, IL-8 contained 321 bp of open reading frame. Interestingly, the predicted protein sequence of 106 aa, contains an ELR motif immediately upstream of the CQC residues, common in all vertebrate IL-8 molecules. Identity levels of the nucleic acid and deduced amino acid sequences of Asian elephant IL-1beta ranged from 68.48 (Squirrel monkey) to 98.57% (African elephant), and 57.78 (Sheep) to 98.47% (African elephant), respectively, whereas that of IL-8 ranged from 72.9% (Human) to 87.8% (African elephant), and 63.2 (human, gorilla, chimpanzee) to 74.5% (African elephant, buffalo), respectively. The phylogenetic analysis based on deduced amino acid sequenced showed that the Asian elephant IL-1beta and IL-8 were most closely related to African elephant. Molecular characterization of these two cytokines, IL-1beta and IL-8, in Asian elephant provides fundamental information necessary to progress the study of functional immune responses in this animal and gives the potential to use them to manipulate the immune response as recombinant proteins. PMID- 26849253 TI - A Compilation of Best Papers. PMID- 26849254 TI - Promoting Healthy Workplaces by Building Cultures of Health and Applying Strategic Communications. AB - OBJECTIVE: The aim of the study was to identify key success elements of employer sponsored health promotion (wellness) programs. METHODS: We conducted an updated literature review, held discussions with subject matter experts, and visited nine companies with exemplary programs to examine current best and promising practices in workplace health promotion programs. RESULTS: Best practices include establishing a culture of health and using strategic communications. Key elements that contribute to a culture of health are leadership commitment, social and physical environmental support, and employee involvement. Strategic communications are designed to educate, motivate, market offerings, and build trust. They are tailored and targeted, multichanneled, bidirectional, with optimum timing, frequency, and placement. CONCLUSIONS: Increased efforts are needed to disseminate lessons learned from employers who have built cultures of health and excellent communications strategies and apply these insights more broadly in workplace settings. PMID- 26849255 TI - The Application of Systems Science to Addressing Obesity at the Workplace: Tapping into Unexplored Potential. AB - OBJECTIVE: The aim of the study was to address the need for explicit recognition that obesity is complex in its biological, social, psychological, and societal determinants and ramifications, and that applications of programs to address obesity at the workplace need to recognize this setting as a complex social environment. Efforts to address this complexity more meaningfully demand intentional application of systems science principles and approaches. METHOD: Along with several relevant examples, a description of systems sciences and the application of its principles to obesity and the workplace setting are presented. CONCLUSIONS: Systems science provides a method to explore large proportions of unexplored potential and unexplained variation in obesity research as applied to the workplace. PMID- 26849256 TI - Single and Combined Exposure to Zinc- and Copper-Containing Welding Fumes Lead to Asymptomatic Systemic Inflammation. AB - OBJECTIVE: Recently, it has been shown that exposure to welding fumes containing both zinc and copper leads to asymptomatic systemic inflammation in humans as shown by an increase of blood C-reactive protein. In the present study, it was investigated which metal is responsible for this effect. METHODS: Fifteen healthy male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc. RESULTS: For each exposure blood C-reactive protein increased. CONCLUSIONS: Copper- and zinc-containing welding fumes are able to induce systemic inflammation. PMID- 26849258 TI - Health Effects of Electromagnetic Fields on Reproductive-Age Female Operators of Plastic Welding Machines in Fuzhou, China. AB - OBJECTIVE: The aim of this study was to investigate the health effects of electromagnetic fields (EMFs) among female operators of plastic welding machines. METHODS: We examined 180 female operators in shoe factories as the exposed group, and 349 female workers from nearby supermarkets as the unexposed group. RESULTS: The mean radiation levels in the vicinity of the welding machines ranged from 51.3 to 368.9 V/m. The prevalence of neurovegetative symptoms increased with higher EMFs exposures (P < 0.05). The prevalence of menstrual disorder was 12.0% in the unexposed group, but was 26.8% and 33.8% in low and high-exposure groups, respectively (P < 0.01). Exposure-response relationships were found between cumulate exposure and neurovegetative symptoms and menstrual disorder (P < 0.05). Serum progesterone (P4) was significantly lower in the exposed groups (P < 0.01). CONCLUSIONS: EMFs exposure was associated with adverse health effects, including neurovegetative symptoms, menstrual disorder, and low level of P4. PMID- 26849257 TI - Effects of Lifetime Occupational Pesticide Exposure on Postural Control Among Farmworkers and Non-Farmworkers. AB - OBJECTIVE: The aim of the study was to assess potential chronic effects of pesticide exposure on postural control, by examining postural balance of farmworkers and non-farmworkers diverse self-reported lifetime exposures. METHODS: Balance was assessed during quiet upright stance under four experimental conditions (2 visual * 2 cognitive difficulty). RESULTS: Significant differences in baseline balance performance (eyes open without cognitive task) between occupational groups were apparent in postural sway complexity. When adding a cognitive task to the eyes open condition, the influence of lifetime exposure on complexity ratios appeared different between occupational groups. Removing visual information revealed a negative association of lifetime exposure with complexity ratios. CONCLUSIONS: Farmworkers and non-farmworkers may use different postural control strategies even when controlling for the level of lifetime pesticide exposure. Long-term exposure can affect somatosensory/vestibular sensory systems and the central processing of sensory information for postural control. PMID- 26849259 TI - Large Machinery-Related Agricultural Injuries Across a Five-State Region in the Midwest. AB - OBJECTIVE: High agricultural injury related mortality and morbidity rates persist. This study addressed a knowledge gap regarding large machinery-related injury magnitude, consequences, and risk factors. METHODS: From randomly selected Midwestern agricultural operations in 1999 and 2001, 7420 eligible households participated. Demographic, exposure, and injury data collected for four 6-month periods used a computer-assisted telephone interview. An a priori causal model enabled survey development, data analysis, and interpretation. Directed acyclic graphs, developed from this model, facilitated potential confounder identification for specific exposures in multivariate analyses. RESULTS: The injury rate was 12.82 events per 1000 persons per year. Increased risk was associated with male gender, increasing age, state of residence, history of prior injury, and increasing hours worked per week. CONCLUSIONS: Large machinery related agricultural injuries can result in significant consequences. Associated increased injury risks require further investigation and targeting of relevant interventions. PMID- 26849260 TI - The Effects of Two Workplace Weight Management Programs and Weight Loss on Health Care Utilization and Costs. AB - OBJECTIVES: The aim of this study was to compare the impact of two worksite weight management (WM [education] and WM+ [education plus counseling]) programs, on health care utilization and costs. Secondarily, compare the intervention groups to an observational control group of obese workers. Finally, evaluate the impact of actual weight loss on these outcomes. METHODS: Estimate the change in the WM and WM+ intervention groups. Using propensity score adjustment compare the two intervention groups with the observational control group; and compare those who lost weight with those who did not. RESULTS: No significant differences between the two intervention groups, or between these intervention groups and the observational control group. Those who lost weight reduced their overall health care costs. CONCLUSIONS: To achieve weight loss and associated morbidity reductions, more extensive and intensive interventions, with more attention to motivation and compliance, are required. PMID- 26849262 TI - The Moderating Effect of Health-Improving Workplace Environment on Promoting Physical Activity in White-Collar Employees: A Multi-Site Longitudinal Study Using Multi-Level Structural Equation Modeling. AB - OBJECTIVE: This longitudinal study aimed to investigate the moderating effect of health-improving workplace environment on relationships between physical activity, self-efficacy, and psychological distress. METHODS: Data were collected from 16 worksites and 129 employees at two time-points. Health-improving workplace environment was measured using the Japanese version of the Environmental Assessment Tool. Physical activity, self-efficacy, and psychological distress were also measured. Multi-level structural equation modeling was used to investigate the moderating effect of health-improving workplace environment on relationships between psychological distress, self efficacy, and physical activity. RESULTS: Psychological distress was negatively associated with physical activity via low self-efficacy. Physical activity was negatively related to psychological distress. Physical activity/fitness facilities in the work environment exaggerated the positive relationship between self-efficacy and physical activity. CONCLUSIONS: Physical activity/fitness facilities in the workplace may promote employees' physical activity. PMID- 26849261 TI - Comparison of Employer Productivity Metrics to Lost Productivity Estimated by Commonly Used Questionnaires. AB - OBJECTIVE: The aim of the study was to assess construct and discriminant validity of four health-related work productivity loss questionnaires in relation to employer productivity metrics, and to describe variation in economic estimates of productivity loss provided by the questionnaires in healthy workers. METHODS: Fifty-eight billing office workers completed surveys including health information and four productivity loss questionnaires. Employer productivity metrics and work hours were also obtained. RESULTS: Productivity loss questionnaires were weakly to moderately correlated with employer productivity metrics. Workers with more health complaints reported greater health-related productivity loss than healthier workers, but showed no loss on employer productivity metrics. Economic estimates of productivity loss showed wide variation among questionnaires, yet no loss of actual productivity. CONCLUSIONS: Additional studies are needed comparing questionnaires with objective measures in larger samples and other industries, to improve measurement methods for health-related productivity loss. PMID- 26849263 TI - Implementing an Integrated Health Protection/Health Promotion Intervention in the Hospital Setting: Lessons Learned From the Be Well, Work Well Study. AB - OBJECTIVE: This study reports findings from a proof-of-concept trial designed to examine the feasibility and estimates the efficacy of the "Be Well, Work Well" workplace intervention. METHODS: The intervention included consultation for nurse managers to implement changes on patient-care units and educational programming for patient-care staff to facilitate improvements in safety and health behaviors. We used a mixed-methods approach to evaluate feasibility and efficacy. RESULTS: Using findings from process tracking and qualitative research, we observed challenges to implementing the intervention due to the physical demands, time constraints, and psychological strains of patient care. Using survey data, we found no significant intervention effects. CONCLUSIONS: Beyond educating individual workers, systemwide initiatives that respond to conditions of work might be needed to transform the workplace culture and broader milieu in support of worker health and safety. PMID- 26849265 TI - Health Conditions as Mediators of the Association Between World Trade Center Exposure and Health-Related Quality of Life in Firefighters and EMS Workers. AB - OBJECTIVE: Studies have reported reduced health-related quality of life (HrQoL) in rescue/recovery workers for years postdisaster. Few have examined specific postdisaster physical and mental health conditions as mediators of the association between exposure to disaster and HrQoL. METHODS: We used the Short Form-12 to measure HrQoL in 7190 male World Trade Center (WTC)-exposed first responders. Potential mediators included physician diagnoses obtained from medical records and mental health conditions obtained from questionnaires. RESULTS: Among moderately and highly WTC-exposed workers, health conditions fully mediated the observed relationship between WTC-exposure and physical health functioning of HrQoL, and substantially mediated the association between WTC exposure and mental health functioning. CONCLUSIONS: Because WTC-related health conditions explain the relationship between WTC-exposure and HrQoL, medical monitoring with treatment of affected populations is necessary to mitigate the adverse effects of WTC-exposure on HrQoL. PMID- 26849264 TI - Risk of Pancreatic Cancer in Female Textile Workers in Shanghai, China, Exposed to Metals, Solvents, Chemicals, and Endotoxin: Follow-Up to a Nested Case-Cohort Study. AB - OBJECTIVE: We studied associations between pancreatic cancer and occupational exposures to metals, solvents, chemicals, and endotoxin in a cohort of female textile workers in Shanghai, China. To assess the longer-term influences of these agents on pancreatic cancer we extended follow-up of this previously studied cohort. METHODS: We utilized a job exposure matrix to assess occupational exposures for 481 pancreatic cancer cases and a randomly selected sub-cohort of 3191 non-cases. We calculated hazard ratios and 95% confidence intervals using Cox proportional hazards modeling adapted for the case-cohort design. RESULTS: We observed a statistically significant trend of increasing hazard ratios associated with solvent exposure, but no associations with any of the remaining occupational exposures, including endotoxin and metals. CONCLUSIONS: Our findings of increasing risk of pancreatic cancer with solvent exposures are consistent with published literature. PMID- 26849266 TI - Pre-Post Evaluation of an Integrated Return to Work Planning Program in Workers' Compensation Assessment Clinics. AB - OBJECTIVE: The aim of this study was to assess the impact of a new workers' compensation medical assessment model on loss of earnings (LOE) benefits duration. METHODS: A medical assessment model was introduced incorporating return to work planning and inclusion of the worker's treating physician. Impact of the program on LOE benefit duration was assessed using a quasi-experimental pre-post study design. Cox PH multivariable regression was adjusted for age, gender, injury severity, time to referral, and industry. RESULTS: The study population comprised 3146 workers: 1794 assessed pre-intervention and 1574 assessed after introduction of the new model. There was a significant reduction in LOE benefit duration for workers assessed in the new model (hazard ratio 1.33, 95% confidence interval 1.23-1.43). CONCLUSIONS: The probability of being off LOE benefits for workers assessed in the new program was 33% greater than for workers assessed in the prior program. PMID- 26849269 TI - Green Commuting in the Health Care Sector: Obstacles and Best Practices. AB - OBJECTIVE: Fossil fuel transportation by health care providers contributes to the prevalence of diseases they treat. We conducted an exploratory study to understand obstacles to, and best practices for, greener commuting among health care providers. METHODS: We surveyed staff of three hospital clinics as to how they commute and why, and interviewed key staff of five hospital leaders in green commuting about their programs. RESULTS: Factors that might change respondents' commuting choices from driving alone included financial incentives, convenience, and solutions to crime and safety concerns. Successful green commuting programs offer benefits including free or reduced transit passes, shuttle buses to transit stations, and free emergency rides home. CONCLUSIONS: Exemplary programs throughout the country demonstrate that modifying those factors within reach can impact the amount of fossil fuel energy used for health care provider transportation. PMID- 26849270 TI - Benchmark Doses Based on Abnormality of WBC or Micronucleus Frequency in Benzene Exposed Chinese Workers. AB - OBJECTIVES: The aim of the study was to calculate benchmark dose for chromosomal damage and reduced white blood cell (WBC) associated with exposure to benzene (BZ). METHODS: A group of 317 exposed workers and 102 controls were examined for WBC count and genotoxicity by micronucleus (MN) frequency. The cumulative exposure concentration of BZ was calculated by ambient air BZ concentration at worksites in conjunction with job type and associated service duration. RESULTS: MN frequency (P < 0.01) was higher and WBC count was lower (P < 0.01) in exposed workers on average than in the controls. MN frequency was a more sensitive than WBC; workers older than 30 were more susceptible to abnormal MN frequency and WBC count reduction than those younger than 30. CONCLUSIONS: Benchmark dose estimates indicated that BZ exposure at levels below the current occupational exposure standard can induce genotoxicity and hematotoxicity. PMID- 26849271 TI - Corporate Health and Wellness and the Financial Bottom Line: Evidence From South Africa. AB - OBJECTIVE: The research objective was to test the hypothesis that corporate health and wellness contributed positively to South African companies' financial results. METHODS: The past share market performance of eligible healthy companies, based on Discovery's Healthy Company Index, was tracked under three investment scenarios and compared with the market performance on the basis of the JSE FTSE All Share Index. RESULTS: The evidence supports the hypothesis that a culture of health and wellness provides a financial advantage, in so far as the portfolio of healthy companies consistently outperformed the market over the selected simulations. CONCLUSIONS: Given the limitations of the investigation, namely small sample size, the brevity of the period of investigation, and the reliance on accessibility sampling, the research provides the first and preliminary evidence supportive of the direct financial benefits of companies' wellness programs. PMID- 26849272 TI - Decreased Activity at the Time of Return to Work Predicts Repeated Sick Leave in Depressed Japanese Patients. PMID- 26849273 TI - Pre-Travel Preparation of Business and Occupational Travelers: Analysis of Global TravEpiNet Consortium. PMID- 26849274 TI - Porphyrin/Platinum(II) C^N^N Acetylide Complexes: Synthesis, Photophysical Properties, and Singlet Oxygen Generation. AB - A new class of substituted porphyrins has been developed in which a different number of cyclometalated Pt(II) C^N^N acetylides and polyethylene glycol (PEG) chains are attached to the meso positions of the porphyrin core, which are meant for photophysical, electrochemical, and in vitro light-induced singlet oxygen ((1)O2) generation studies. All of these Zn(II) porphyrin-Pt(II) C^N^N acetylide conjugates show moderate to high (PhiDelta =0.55 to 0.63) singlet oxygen generation efficiency. The complexes are soluble in organic solvents but, despite the PEG substituents, slowly aggregate in aqueous solvent systems. These conjugates also exhibit interesting photophysical properties, including near complete photoinduced energy transfer (PEnT) through the rigid acetylenic bond(s) from the Pt(II) C^N^N antenna units to the Zn(II) porphyrin core, which shows sensitized luminescence, as shown by quenching of Pt(II) C^N^N-based luminescence. Electrochemical measurements show a set of redox processes that are approximately the sum of what is observed for the Pt(II) C^N^N acetylide and Zn(II) porphyrin units. UV/Vis spectroscopic properties are supported by DFT calculations. PMID- 26849275 TI - Dietary mannitol increased the absorption of calcium and magnesium in rats. AB - The effect of mannitol on bone-related mineral absorption and retention and the mechanism was investigated in this study. Fourteen 8-week-old male Wistar rats in experiment 1 and same number and age cecectomized Wistar male rats in experiment 2 were divided into two subgroups of seven animals, respectively, fed diets containing 0 or 4% mannitol for 28 days. Mineral balance tests were determined twice during days 8-12 and days 22-26, and the rats were slaughtered on day 28 both in experiment 1 and experiment 2. The whole caecum and colon were collected with the content to analyse tissue weight, content weight, content's pH and moisture, organic acids' concentration and mineral levels. In experiment 1, Ca absorption and retention and Mg absorption were significantly increased by mannitol feeding during days 8-12. Caecal total weight, tissue weight and content weight were increased, the pH of caecum and colon was reduced, and the concentrations of caecal short-chain fatty acids (SCFAs) were modified by mannitol feeding. In experiment 2, during days 8-12 and days 22-26, Ca absorption and retention were significantly lowered by mannitol feeding in cecectomized rats; however, mannitol feeding decreased Mg absorption during days 8-12, but did not impact Mg retention. Colonic total weight, tissue weight and content weight were significantly increased, and colonic pH was reduced by mannitol feeding. In conclusion, dietary mannitol increased the absorption of Ca and Mg and the caecum markedly contributed to this promoting effect of mannitol. PMID- 26849276 TI - Enigma of painful diabetic neuropathy: can we use the basic science, research outcomes and real-world data to help improve patient care and outcomes? AB - The pathogenesis of painful diabetic neuropathy (PDN) is very complex and its detailed understanding often beyond the remit of the diabetologist or the diabetes multidisciplinary team. Nonetheless it is a very common and difficult to treat complication of diabetes, with significant co-morbidity and mortality, and some basic understanding may help the health care professional with its day to day management. In this review, we discuss the basic pathological mechanisms of PDN, and its clinical manifestations, and present both scientific and real world data on its management, in an attempt to help improve patient care and outcomes. PMID- 26849277 TI - Promoting mobility and reducing length of stay in hospitalized general medicine patients: A quality-improvement project. AB - OBJECTIVE: To determine whether a multidisciplinary mobility promotion quality improvement (QI) project would increase patient mobility and reduce hospital length of stay (LOS). PATIENTS AND METHODS: Implemented using a structured QI model, the project took place between March 1, 2013 and March 1, 2014 on 2 general medicine units in a large academic medical center. There were 3352 patients admitted during the QI project period. The Johns Hopkins Highest Level of Mobility (JH-HLM) scale, an 8-point ordinal scale ranging from bed rest (score = 1) to ambulating >=250 feet (score = 8), was used to quantify mobility. Changes in JH-HLM scores were compared for the first 4 months of the project (ramp-up phase) versus 4 months after project completion (post-QI phase) using generalized estimating equations. We compared the relative change in median LOS for the project months versus 12 months prior among the QI units, using multivariable linear regression analysis adjusting for 7 demographic and clinically relevant variables. RESULTS: Comparing the ramp-up versus post-QI phases, patients reaching JH-HLM's ambulation status increased from 43% to 70% (P < 0.001), and patients with improved JH-HLM mobility scores between admission and discharge increased from 32% to 45% (P < 0.001). For all patients, the QI project was associated with an adjusted median LOS reduction of 0.40 (95% confidence interval [CI]: -0.57 to -0.21, P < 0.001) days compared to 12 months prior. A subgroup of patients expected to have a longer LOS (expected LOS >7 days), were associated with a significantly greater adjusted median reduction in LOS of 1.11 (95% CI: 1.53 to -0.65, P < 0.001) days. Increased mobility was not associated with an increase in injurious falls compared to 12 months prior on the QI units (P = 0.73). CONCLUSIONS AND RELEVANCE: Active prevention of a decline in physical function that commonly occurs during hospitalization may be achieved with a structured QI approach. In an adult medicine population, our QI project was associated with improved mobility, and this may have contributed to a reduction in LOS, particularly for more complex patients with longer expected hospital stay. Journal of Hospital Medicine 2016. (c) 2016 Society of Hospital Medicine. PMID- 26849278 TI - Highly Crystallized Na2CoFe(CN)6 with Suppressed Lattice Defects as Superior Cathode Material for Sodium-Ion Batteries. AB - Prussian blue and its analogues have received particular attention as superior cathodes for Na-ion batteries due to their potential 2-Na storage capacity (~170 mAh g(-1)) and low cost. However, most of the Prussian blue compounds obtained from the conventional synthetic routes contain large amounts of Fe(CN)6 vacancies and coordinated water molecules, which leads to the collapse of cyano-bridged framework and serious deterioration of their Na-storage ability. Herein, we propose a facile citrate-assisted controlled crystallization method to obtain low defect Prussian blue lattice with greatly improved Na-storage capacity and cycling stability. As an example, the as-prepared Na2CoFe(CN)6 nanocrystals demonstrate a reversible 2-Na storage reaction with a high specific capacity of 150 mAh g(-1) and a ~ 90% capacity retention over 200 cycles, possibly serving as a low cost and high performance cathode for Na-ion batteries. In particular, the synthetic strategy described in this work may be extended to other coordination framework materials for a wide range of energy conversion and storage applications. PMID- 26849279 TI - Interscalene catheters--should we give them the cold shoulder? PMID- 26849280 TI - Management of chronic pruritus with a UV filtering topical cream. AB - Chronic pruritus is a common dermatological condition affecting 10-13% of the general population. UVB phototherapy has been demonstrated to be effective in relieving the symptoms of pruritus. However, phototherapy is rarely administered because the treatment is time-consuming and expensive, when compared to other topical drugs. In previous works, it has been reported that a topical cream, which selectively filters solar UVB can be used as a convenient alternative to traditional phototherapy. Here, we report the results of a pilot study aimed at assessing the effectiveness of the cream for treating pruritus. Seven patients with pruritus symptoms were included in the study. After 3 months of treatment (3 sessions per week), all patients noted improvement in pruritus symptoms. These preliminary results demonstrate that the novel topical cream could provide a convenient, low cost treatment for chronic pruritus patients. PMID- 26849281 TI - Exercise-induced oxidatively damaged DNA in humans: evaluation in plasma or urine? AB - Physical exercise can induce oxidative damage in humans. 8-Hydroxy-2' deoxyguanosine (8-OHdG) is a widely known biomarker of DNA oxidation, which can be determined in blood and urine. The aim of the present study was to compare these two biological fluids in terms of which is more suitable for the estimation of the oxidative damage of DNA by measuring the concentration of 8-OHdG one hour after maximal exercise by enzyme immunoassay. The concentration of 8-OHdG increased with exercise only in plasma (p < 0.001), and values differed between exercise tests in both plasma and urine (p < 0.05). In conclusion, plasma appears to be more sensitive to exercise-induced 8-OHdG changes than urine and, hence, a more appropriate medium for assessing oxidative damage of DNA, although the poor repeatability of the measurement needs to be addressed in future studies. PMID- 26849282 TI - The Use of the Sternocleidomastoid Flap Helps Reduce Complications After Free Jejunal Flap Reconstructions in Total Laryngectomy and Cervical Esophagectomy Defects. AB - PURPOSE: Esophageal reconstruction after tumor extirpation or ingestion injury is a difficult problem for the reconstructive plastic surgeon. Free tubed fasciocutaneous flaps and intestinal flaps have become the mainstay for reconstruction. The free jejunal flap has the advantage of replacing like-with like tissue and having lower fistula rates. Additionally, the "mesenteric wrap" modification and prophylactic pectoralis major muscle have been described to further decrease anastomotic leaks and fistulae. The purpose of this study was to describe the use of the prophylactic pedicled sternocleidomastoid (SCM) flap for prevention of anastomotic leaks and fistulae. METHODS: A retrospective review of patients who underwent reconstruction of circumferential pharyngoesophageal defects with a free jejunal flap by a single surgeon from 2008 to 2012 was performed. Those who received a prophylactic pedicled SCM flap to reinforce one of their jejunal anastomoses were selected for this study, and their outcomes were analyzed. Patients' demographics, comorbidities, complications, and clinical outcomes were collected and analyzed. RESULTS: Three patients underwent reinforcement of one jejunal anastomosis with a pedicled SCM flap. The mean age was 60 years, and average follow-up was 27 months. Two patients received postoperative radiation, and one patient received both preoperative and postoperative radiation. The recipient vessels included the facial artery, internal jugular vein, and facial vein. The flap survival rate was 100%. There was 1 stricture and 1 fistula that occurred at the anastomoses without the SCM muscle reinforcement. There were no complications at the jejunal anastomotic sites that were reinforced with the SCM muscle. Of the 6 anastomotic sites in 3 patients, there was a 0% fistula rate and 0% stricture rate at the sites reinforced with the SCM muscle versus a 33% fistula rate and a 33% stricture rate at the sites without the SCM muscle flap. One patient was diagnosed with local tumor recurrence and eventually succumbed to the progression of their disease. All patients were able to tolerate an oral diet without supplemental feeds. All patients were able to achieve intelligible speech via an electrolarynx or esophageal speech. CONCLUSION: Reconstruction of pharyngoesophageal defects can be technically challenging and requires extensive planning and careful execution. The free jejunal flap restores alimentary continuity with good functional outcomes. Fistula rates may be decreased with the use of a prophylactic SCM flap to reinforce the jejunal anastomosis. PMID- 26849283 TI - Promise and Limitations of Big Data Research in Plastic Surgery. AB - BACKGROUND: The use of "Big Data" in plastic surgery outcomes research has increased dramatically in the last 5 years. This article addresses some of the benefits and limitations of such research. METHODS: This is a narrative review of large database studies in plastic surgery. RESULTS: There are several benefits to database research as compared with traditional forms of research, such as randomized controlled studies and cohort studies. These include the ease in patient recruitment, reduction in selection bias, and increased generalizability. As such, the types of outcomes research that are particularly suited for database studies include determination of geographic variations in practice, volume outcome analysis, evaluation of how sociodemographic factors affect access to health care, and trend analyses over time. The limitations of database research include data which are limited only to what was captured in the database, high power which can cause clinically insignificant differences to achieve statistical significance, and fishing which can lead to increased type I errors. The National Surgical Quality Improvement Project is an important general surgery database that may be useful for plastic surgeons because it is validated and has a large number of patients after over a decade of collecting data. The Tracking Operations and Outcomes for Plastic Surgeons Program is a newer database specific to plastic surgery. CONCLUSIONS: Databases are a powerful tool for plastic surgery outcomes research. It is critically important to understand their benefits and limitations when designing research projects or interpreting studies whose data have been drawn from them. For plastic surgeons, National Surgical Quality Improvement Project has a greater number of publications, but Tracking Operations and Outcomes for Plastic Surgeons Program is the most applicable database for plastic surgery research. PMID- 26849284 TI - Short-Term Complications Associated With Acellular Dermal Matrix-Assisted Direct to-Implant Breast Reconstruction. AB - BACKGROUND: Although direct-to-implant breast reconstruction is a more concise procedure than 2-stage expander/implant reconstruction, it is less frequently performed. Skeptics of direct-to-implant reconstruction cite risk of postoperative complications as a reason for its rejection. To determine whether these perceptions are valid, we evaluated our 13-year experience of acellular dermal matrix (ADM)-assisted, direct-to-implant breast reconstruction. We report complication and reoperation rates associated with this technique as well as predictors for these outcomes. METHODS: This retrospective study included all patients who underwent immediate, ADM-assisted, direct-to-implant, breast reconstruction from December 2001 to May 2014 at 2 practices. Postoperative complications, defined as those occurring within the first 12 months after reconstructive surgery, were evaluated. Univariate/multivariate analyses were performed to determine the influence of patient-, breast-, and surgery-related characteristics on the development of complications. RESULTS: A total of 1584 breast reconstructions (721 bilateral, 142 unilateral) in 863 patients were performed; 35% were oncologic, and 65% were prophylactic reconstructions. Complication rate was 8.6% and included skin necrosis (5.9%), infection (3.0%), implant loss (2.9%), seroma (1.1%), and hematoma (0.9%). Reoperative rate in breasts with complications was 3.2%. Age 50 years or older, smoking, nonnipple sparing mastectomy, and implant size of 600 mL or greater strongly predicted the development of complications (P < 0.001). CONCLUSIONS: Our cumulative 13-year experience demonstrates that immediate, ADM-assisted, direct-to-implant breast reconstruction is safe, effective, and reliable. Complication and reoperation rates are less than 10% and are comparable to those reported for 2-stage procedures in the published literature. PMID- 26849285 TI - What anatomy is clinically useful and when should we be teaching it? AB - Anatomy teaching, once thought of as being the cornerstone of medical education, has undergone much change in the recent years. There is now growing concern for falling standards in medical graduates' anatomical knowledge, coupled with a reduction in teaching time and appropriately qualified teaching staff. With limited contact hours available to teach this important discipline, it is essential to consider what anatomy is taught within the medical curriculum to ensure it is fit for clinical practice. The views of medical students, junior doctors, and consultants were obtained from the University of Nottingham and the Trent Deanery in Nottingham, United Kingdom, to establish what core anatomical knowledge they feel medical students should study and assimilate during preclinical training. All participants felt strongly that medical students should be adept at interpreting modern diagnostic images before entering their clinical placement or specialty. Respondents proposed more teaching emphasis should be placed on specific anatomical areas (including lymphatic drainage and dermatome innervation) and illustrated other areas where less detailed teaching was appropriate. Recommendations from our study highlight a need for greater clinical emphasis in anatomy teaching during preclinical years. To successfully achieve this, it is essential that clinicians become integrally involved in the design and delivery of future medical undergraduate anatomy courses. Anat Sci Educ 9: 468-475. (c) 2016 American Association of Anatomists. PMID- 26849286 TI - Sexual Behavior, Satisfaction, and Contraceptive Use Among Postpartum Women. AB - INTRODUCTION: This study aimed to 1) describe the behaviors and timing of the first sexual activity postpartum, 2) compare characteristics of women who return to vaginal intercourse by 6 weeks postpartum to those who initiate intercourse after 6 weeks, 3) evaluate contraceptive use of postpartum women, and 4) describe the physical and emotional satisfaction with the first sexual activity postpartum. METHODS: This prospective study recruited participants during prenatal visits or postpartum prior to hospital discharge. Women completed an initial survey regarding pregnancy intendedness, contraceptive history, breastfeeding plans, sexual activity, satisfaction, and initiation. Postpartum surveys were conducted every 2 weeks starting 6 weeks after birth until 12 weeks or return to vaginal sexual intercourse. RESULTS: A total of 370 participants were recruited; 304 (82%) were followed to first intercourse. By life table analysis at 6 weeks (42 days) postpartum, 132 (43%) of women had resumed sexual intercourse, but only 65 (49%) of those women reported using contraception. There were no significant demographic or obstetric differences by timing of resumption of intercourse. However, when controlling for these characteristics, women who reported using contraception at 6 weeks postpartum were 1.8 times (95% confidence interval [CI], 1.2-3.2; P = .015) more likely to have had vaginal intercourse by 6 weeks postpartum compared to women who were not using contraception then. By 12 weeks postpartum, 341 (92%) of women had resumed vaginal intercourse. Psychological and physical satisfaction during sex was lower both during pregnancy and after giving birth, relative to satisfaction before pregnancy (P < .001). DISCUSSION: By 6 weeks postpartum, 4 in 10 women had resumed vaginal intercourse, with only half using contraception. Counseling regarding postpartum contraception should meet normative behavior. Thus, contraceptive plans need to be established during prenatal care, and the postpartum visit should occur earlier than the current standard time of 6 weeks. PMID- 26849287 TI - Development and validation of a noninvasive prediction model for nonalcoholic steatohepatitis resolution after lifestyle intervention. AB - Liver biopsy is the gold standard method to assess nonalcoholic steatohepatitis (NASH) resolution after therapeutic interventions. We developed and validated a simple and noninvasive scoring system to predict NASH resolution without fibrosis worsening after 1 year of lifestyle intervention. This was a prospective cohort study conducted in 261 patients with histologically proven NASH who were treated with lifestyle changes for 52 weeks and underwent a second liver biopsy to confirm NASH resolution. We divided the data into development (140 subjects) and validation (121 individuals) sets. NASH resolution occurred in 28% (derivation group) and 27% (validation group). At the multivariable analysis, weight loss (odds ratio [OR] = 2.75, 95% confidence interval [CI] 1.65-4.58; P < 0.01), type 2 diabetes (OR = 0.04, 95% CI 0.005-0.49; P = 0.01), normal levels of alanine aminotransferase at the end of intervention (OR = 9.84, 95% CI 2.21-44.1; P < 0.01), age (OR = 0.89, 95% CI 0.83-0.97; P = 0.01), and a nonalcoholic fatty liver activity score >=5 (OR = 0.08, 95% CI 0.01-0.43; P < 0.01) were independent predictors of NASH resolution. The area under the receiver operating characteristic curve of the selected model was 0.956 and 0.945 in the derivation and validation cohorts, respectively. Using a score threshold of <=46.15, negative predictive values were 92% in the derivation and validation groups, respectively. By applying a cutoff >=69.72, positive predictive values were 92% and 89% in the derivation and validation groups, respectively. Using both cutoffs, a liver biopsy would have been avoided in 229 (88%) of 261 patients, with a correct prediction in 209 (91%) CONCLUSIONS: A noninvasive prediction model including weight loss, type 2 diabetes, alanine aminotransferase normalization, age, and a nonalcoholic fatty liver activity score >=5 may be useful to identify NASH resolution in patients under lifestyle intervention. (Hepatology 2016;63:1875-1887). PMID- 26849288 TI - Silk as a Biomaterial to Support Long-Term Three-Dimensional Tissue Cultures. AB - Tissue engineering has broad and diverse impacts on a variety of different applications from tissue regeneration to drug screening. While two-dimensional (2 D) cell culture platforms are suitable for tissue interfaces where planar surfaces are relevant, three dimensional (3-D) tissue models have enhanced relevance and sustainability over 2-D devices. The improvements between 2-D and 3 D functions and sustainability are related to the limitations of 2-D systems to support proper cellular morphology and signaling over time, resulting in cell overgrowth or changes in viability. For sustainable (long-term) cultures, 3-D silk protein scaffolds provide biocompatibility, porous features for transport, robust yet tunable mechanical properties, retain size and open porous structures for extended time frames due to slow proteolytic biodegradation, avoid specific cell signaling, and require no chemical cross-linking. Silk degradation can be extended for months to years without premature collapse of structures (that would result in necrosis) to support cell interactions during slow remodeling toward native tissue. Silk can also be fabricated into different material formats, such as hydrogels, tubes, sponges, composites, fibers, microspheres, and thin films, providing versatile platforms and interfaces for a variety of different applications. For sustainable tissue engineering applications, many formats have been used, including silk ionmer hydrogels that have been cultured for up to 8 weeks and porous silk scaffolds that have been cultured for up to 6 months. In this review, we highlight some of our tissue engineering work related to long term in vitro cultures. While each tissue engineered system (adipose tissue, cortical brain tissue, intestine, kidney tissue, bone) is unique, they all use silk biomaterials as a base scaffolding material to achieve sustainable cultivation. Sustainability is important for studies that extend past a few weeks to study acute and chronic impacts of treatments, disease models, and other related applications in the field of tissue engineering. PMID- 26849289 TI - The role of the hippocampus in memory and mental construction. AB - Much has been learned about the processes that support the remembrance of past autobiographical episodes and their importance for a number of cognitive tasks. This work has focused on hippocampal contributions to constructing coherent mental representations of scenarios for these tasks, which has opened up new questions about the underlying hippocampal mechanisms. We propose a new framework to answer these questions, which incorporates task demands that prompt hippocampal contributions to mental construction, the online formation of such mental representations, and how these demands relate to the functional organization of the hippocampus. Synthesizing findings from autobiographical memory research, our framework suggests that the interaction of two task characteristics influences the recruitment of the hippocampus: (1) the degree of task open-endedness (quantified by the presence/absence of a retrieval framework) and (2) the degree to which the integration of perceptual details is required. These characteristics inform the relative weighting of anterior and posterior hippocampal involvement, following an organizational model in which the anterior and posterior hippocampus support constructions on the basis of conceptual and perceptual representations, respectively. The anticipated outcome of our framework is a refined understanding of hippocampal contributions to memory and to the host of related cognitive functions. PMID- 26849290 TI - Pathways to Advancing Aging Policy-Relevant Research in Academic Settings. AB - Policy-level changes have a significant influence on the health and well-being of aging populations. Yet there is often a gap between scientific knowledge and policy action. Although previous research has identified barriers and facilitators to effective knowledge translation, little attention has been given to the role of academic institutions in knowledge generation. This exploratory focus group study examines barriers and pathways to developing and maintaining an aging policy-relevant research agenda in academic settings, and additional challenges associated with minority group membership in this pursuit. Participants were personally committed to conducting policy-relevant research despite institutional barriers such as fewer funding opportunities and less value attributed to their research, particularly in the context of tenure and promotion. Although many viewed their research as an opportunity to make a difference, especially for underserved older adult populations, a number of minority group participants expressed that their policy research interests were marginalized. Participants offer individual and institutional-level strategies for addressing barriers, including collaborating with community members and colleagues and engaging mentors within and outside of their academic institutions. Reframing the valuation of policy research through the diversification of funding and publishing opportunities can better support scholars engaged in aging policy-relevant research. PMID- 26849293 TI - Neonatal developmental care in infant pain management and internalizing behaviours at 18 months in prematurely born children. AB - BACKGROUND: Very preterm infants are exposed to adverse stressful experiences, which may result in long-term behavioural outcomes. The developmental care practices, including pain management and environmental support, can minimize the effects of stress exposure. However, developmental care quality levels may vary among Neonatal Intensive Care Units (NICUs) and little is known about how differences in developmental care quality affect long-term behavioural outcomes. The aim of this study was to examine the relation between quality levels NICUs developmental care and behaviour problems at 18 months corrected age in preterm children. METHODS: The behaviour of 134 preterm children from 22 NICUs and 123 full-term controls was examined using the questionnaire Child Behaviour Checklist 11/2-5. We compared the behavioural profile of children by splitting NICUs into units with high- and low quality of developmental care according to two main care factors: (1) infant centered care (ICC) index, and (2) infant pain management (IPM) index. RESULTS: Preterm children from low-care units in IPM group reported higher scores in Internalizing Problems, compared to children from high-care units. No differences were found between preterm children from high-care in IPM and full-term children. No significant IPM effect was found for externalizing problems. No significant ICC effect emerged both for internalizing and externalizing problems. CONCLUSIONS: Findings suggest that higher quality of developmental care related to infant pain management can mitigate behavioural problems at 18 months in children born preterm, to such an extent that preterm children exhibit a behavioural profile similar to that displayed by full-term children. PMID- 26849294 TI - Fine-tuning for the tropics: application of eDNA technology for invasive fish detection in tropical freshwater ecosystems. AB - Invasive species pose a major threat to aquatic ecosystems. Their impact can be particularly severe in tropical regions, like those in northern Australia, where >20 invasive fish species are recorded. In temperate regions, environmental DNA (eDNA) technology is gaining momentum as a tool to detect aquatic pests, but the technology's effectiveness has not been fully explored in tropical systems with their unique climatic challenges (i.e. high turbidity, temperatures and ultraviolet light). In this study, we modified conventional eDNA protocols for use in tropical environments using the invasive fish, Mozambique tilapia (Oreochromis mossambicus) as a detection model. We evaluated the effects of high water temperatures and fish density on the detection of tilapia eDNA, using filters with larger pores to facilitate filtration. Large-pore filters (20 MUm) were effective in filtering turbid waters and retaining sufficient eDNA, whilst achieving filtration times of 2-3 min per 2-L sample. High water temperatures, often experienced in the tropics (23, 29, 35 degrees C), did not affect eDNA degradation rates, although high temperatures (35 degrees C) did significantly increase fish eDNA shedding rates. We established a minimum detection limit for tilapia (1 fish/0.4 megalitres/after 4 days) and found that low water flow (3.17 L/s) into ponds with high fish density (>16 fish/0.4 megalitres) did not affect eDNA detection. These results demonstrate that eDNA technology can be effectively used in tropical ecosystems to detect invasive fish species. PMID- 26849295 TI - Host manipulation by cancer cells: Expectations, facts, and therapeutic implications. AB - Similar to parasites, cancer cells depend on their hosts for sustenance, proliferation and reproduction, exploiting the hosts for energy and resources, and thereby impairing their health and fitness. Because of this lifestyle similarity, it is predicted that cancer cells could, like numerous parasitic organisms, evolve the capacity to manipulate the phenotype of their hosts to increase their own fitness. We claim that the extent of this phenomenon and its therapeutic implications are, however, underappreciated. Here, we review and discuss what can be regarded as cases of host manipulation in the context of cancer development and progression. We elaborate on how acknowledging the applicability of these principles can offer novel therapeutic and preventive strategies. The manipulation of host phenotype by cancer cells is one more reason to adopt a Darwinian approach in cancer research. PMID- 26849296 TI - A Cell-ebration of Induced Pluripotency. PMID- 26849297 TI - Mom Knows Best: Imprinted Control of Hematopoietic Stem Cell Quiescence. AB - The mechanisms by which imprinted loci control activity of hematopoietic stem cells (HSCs) are not known. In this issue of Cell Stem Cell, Qian et al. (2016) demonstrate that non-coding RNAs expressed by the maternal-imprinted locus Dlk1 Gtl2 maintain HSC self-renewal through the inhibition of PI3K-mTOR signaling, mitochondrial biogenesis, and metabolic activity. PMID- 26849298 TI - Activated Muscle Satellite Cells Chase Ghosts. AB - The in vivo behaviors of skeletal muscle stem cells, i.e., satellite cells, during homeostasis and after injury are poorly understood. In this issue of Cell Stem Cell, Webster et al. (2016) now perform a tour de force intravital microscopic analysis of this population, showing that "ghost fiber" remnants act as scaffolds to guide satellite cell divisions after injury. PMID- 26849299 TI - Compacting Chromatin to Ensure Muscle Satellite Cell Quiescence. AB - Satellite cells comprise a pool of quiescent stem cells that repair muscle damage, but the mechanisms enforcing their quiescence are poorly defined. In this issue of Cell Stem Cell, Boonsanay et al. (2016) show that the histone methyltransferase Suv4-20H1 maintains satellite cell quiescence by promoting a heterochromatic state through transcriptional repression of the myogenic master regulator MyoD. PMID- 26849301 TI - Time to Relax: Mechanical Stress Release Guides Stem Cell Responses. AB - Stem cells integrate spatiotemporal cues, including the mechanical properties of their microenvironment, into their fate decisions. Chaudhuri et al. (2015) show that the ability of the extracellular matrix to dissipate cell-induced forces, referred to as stress-relaxation, is a key mechanical signal influencing stem cell fate and function. PMID- 26849300 TI - Naive versus Primed: It's Now Three-Dimensional. AB - We are only beginning to understand the higher-order chromatin structure of pluripotent stem cells and its relevance to cell fate. Three recent studies used different approaches to reconstruct the 3D chromatin landscape of naive and primed pluripotent cells, unveiling common features as well as differences between these two states. PMID- 26849302 TI - CDX2: Linking Cell and Patient Fates in Colon Cancer. AB - Administering adjuvant chemotherapy to stage II colon cancer patients is controversial due to limited benefit observed for this subpopulation. Recently, Dalerba et al. (2016) identified a subgroup of stage II patients that might benefit from adjuvant chemotherapy based on lack of CDX2 expression in their cancer stem cells. PMID- 26849303 TI - 10 Questions: Clinical Outlook for iPSCs. AB - In an interview, we recently asked four leaders in the field to share their insights with us on the clinical outlook for hiPSCs. We present highlights from their responses here. PMID- 26849306 TI - Timeline: iPSCs--The First Decade. AB - Research into induced pluripotent stem cells (iPSCs) has expanded at a remarkable pace in the decade since Shinya Yamanaka and Kazutoshi Takahashi first reported their groundbreaking discovery in 2006. This Timeline highlights the key events in the development of this field, including basic insights into the production of iPSCs and how they have been applied to improve our understanding and treatment of human disease. To view this Timeline, open or download the PDF. You can also listen to the associated interview with Debbie Sweet, Editor of Cell Stem Cell, and Elena Porro, Editor of Cell. PAPERCLIP. PMID- 26849305 TI - A miR-34a-Numb Feedforward Loop Triggered by Inflammation Regulates Asymmetric Stem Cell Division in Intestine and Colon Cancer. AB - Emerging evidence suggests that microRNAs can initiate asymmetric division, but whether microRNA and protein cell fate determinants coordinate with each other remains unclear. Here, we show that miR-34a directly suppresses Numb in early stage colon cancer stem cells (CCSCs), forming an incoherent feedforward loop (IFFL) targeting Notch to separate stem and non-stem cell fates robustly. Perturbation of the IFFL leads to a new intermediate cell population with plastic and ambiguous identity. Lgr5+ mouse intestinal/colon stem cells (ISCs) predominantly undergo symmetric division but turn on asymmetric division to curb the number of ISCs when proinflammatory response causes excessive proliferation. Deletion of miR-34a inhibits asymmetric division and exacerbates Lgr5+ ISC proliferation under such stress. Collectively, our data indicate that microRNA and protein cell fate determinants coordinate to enhance robustness of cell fate decision, and they provide a safeguard mechanism against stem cell proliferation induced by inflammation or oncogenic mutation. PMID- 26849304 TI - Stem and Progenitor Cell-Based Therapy of the Central Nervous System: Hopes, Hype, and Wishful Thinking. AB - A variety of neurological disorders are attractive targets for stem and progenitor cell-based therapy. Yet many conditions are not, whether by virtue of an inhospitable disease environment, poorly understood pathophysiology, or poor alignment of donor cell capabilities with patient needs. Moreover, some disorders may be medically feasible targets but are not practicable, in light of already available treatments, poor risk-benefit and cost-benefit profiles, or resource limitations. This Perspective seeks to define those neurological conditions most appropriate for cell replacement therapy by considering its potential efficacy and clinical feasibility in those disorders, as well as potential impediments to its application. PMID- 26849308 TI - Single-Molecule Encapsulation: A Straightforward Route to Highly Stable and Printable Enzymes. AB - A mild, fast, and sequence-independent method for controlled enzyme immobilization is presented. This novel approach involves the encapsulation of single-enzyme molecules and the covalent attachment of these nanobiocatalysts onto surfaces. Fast and mild immobilization conditions, combined with low nonspecific adsorption on hydrophobic substrates, enables well-defined surface patterns via microcontact printing. The biohybrid materials show enhanced activity in organic solvents. PMID- 26849307 TI - A Robust Workflow for Native Mass Spectrometric Analysis of Affinity-Isolated Endogenous Protein Assemblies. AB - The central players in most cellular events are assemblies of macromolecules. Structural and functional characterization of these assemblies requires knowledge of their subunit stoichiometry and intersubunit connectivity. One of the most direct means for acquiring such information is so-called "native mass spectrometry (MS)", wherein the masses of the intact assemblies and parts thereof are accurately determined. It is of particular interest to apply native MS to the study of endogenous protein assemblies-i.e., those wherein the component proteins are expressed at endogenous levels in their natural functional states, rather than the overexpressed (sometimes partial) constructs commonly employed in classical structural studies, whose assembly can introduce stoichiometry artifacts and other unwanted effects. To date, the application of native MS to the elucidation of endogenous protein complexes has been limited by the difficulty in obtaining pristine cell-derived assemblies at sufficiently high concentrations for effective analysis. Here, to address this challenge, we present a robust workflow that couples rapid and efficient affinity isolation of endogenous protein complexes with a sensitive native MS readout. The resulting workflow has the potential to provide a wealth of data on the stoichiometry and intersubunit connectivity of endogenous protein assemblies-information that is key to successful integrative structural elucidation of biological systems. PMID- 26849309 TI - Comparison between PEEK and Ti6Al4V concerning micro-scale abrasion wear on dental applications. AB - In the oral cavity, abrasive wear is predictable at exposed tooth or restorative surfaces, during mastication and tooth brushing. Also, wear can occur at contacting surfaces between the Ti-based prosthetic structures and implants in presence of abrasive compounds from food or toothpaste. Thus, the aim of this work was to compare the abrasive wear resistance of PEEK and Ti6Al4V on three body abrasion related to different hydrated silica content and loads. Surfaces of Ti6Al4V or PEEK cylinders (8mm diameter and 4mm height) were wet ground on SiC papers and then polished with 1um diamond paste. After that, surfaces were ultrasonically cleaned in propyl alcohol for 15min and then in distilled water for 10min. Micro-scale abrasion tests were performed at 60rpm and on different normal loads (0.4, 0.8 or 1.2N) after 600 ball revolutions using suspensions with different weight contents of hydrated silica. After abrasive tests, wear scars on flat samples were measured to quantify the wear volume and characterized by scanning electron microscope (SEM) to identify the dominant wear mechanisms. Results showed a higher volume loss rate on PEEK than that recorded on Ti6Al4V,, when subjected to three-body abrasion tests involving hydrated silica suspensions. An increase in volume loss was noted on both tested materials when the abrasive content or load was increased. PEEK was characterized by less wear resistance than that on Ti6Al4V after micro-scale abrasion wear in contact with hydrated silica particles, as commonly found in toothpastes. PMID- 26849310 TI - Contributions of ancestral inter-species recombination to the genetic diversity of extant Streptomyces lineages. AB - Streptomyces species produce many important antibiotics and have a crucial role in soil nutrient cycling. However, their evolutionary history remains poorly characterized. We have evaluated the impact of homologous recombination on the evolution of Streptomyces using multi-locus sequence analysis of 234 strains that represent at least 11 species clusters. Evidence of inter-species recombination is widespread but not uniform within the genus and levels of mosaicism vary between species clusters. Most phylogenetically incongruent loci are monophyletic at the scale of species clusters and their subclades, suggesting that these recombination events occurred in shared ancestral lineages. Further investigation of two mosaic species clusters suggests that genes acquired by inter-species recombination may have become fixed in these lineages during periods of demographic expansion; implicating a role for phylogeography in determining contemporary patterns of genetic diversity. Only by examining the phylogeny at the scale of the genus is apparent that widespread phylogenetically incongruent loci in Streptomyces are derived from a far smaller number of ancestral inter species recombination events. PMID- 26849311 TI - Emerging pathogens of gilthead seabream: characterisation and genomic analysis of novel intracellular beta-proteobacteria. AB - New and emerging environmental pathogens pose some of the greatest threats to modern aquaculture, a critical source of food protein globally. As with other intensive farming practices, increasing our understanding of the biology of infections is important to improve animal welfare and husbandry. The gill infection epitheliocystis is increasingly problematic in gilthead seabream (Sparus aurata), a major Mediterranean aquaculture species. Epitheliocystis is generally associated with chlamydial bacteria, yet we were not able to localise chlamydial targets within the major gilthead seabream lesions. Two previously unidentified species within a novel beta-proteobacterial genus were instead identified. These co-infecting intracellular bacteria have been characterised using high-resolution imaging and genomics, presenting the most comprehensive study on epitheliocystis agents to date. Draft genomes of the two uncultured species, Ca. Ichthyocystis hellenicum and Ca. Ichthyocystis sparus, have been de novo sequenced and annotated from preserved material. Analysis of the genomes shows a compact core indicating a metabolic dependency on the host, and an accessory genome with an unprecedented number of tandemly arrayed gene families. This study represents a critical insight into novel, emerging fish pathogens and will be used to underpin future investigations into the bacterial origins, and to develop diagnostic and treatment strategies. PMID- 26849312 TI - Interactions between hydrology and water chemistry shape bacterioplankton biogeography across boreal freshwater networks. AB - Disentangling the mechanisms shaping bacterioplankton communities across freshwater ecosystems requires considering a hydrologic dimension that can influence both dispersal and local sorting, but how the environment and hydrology interact to shape the biogeography of freshwater bacterioplankton over large spatial scales remains unexplored. Using Illumina sequencing of the 16S ribosomal RNA gene, we investigate the large-scale spatial patterns of bacterioplankton across 386 freshwater systems from seven distinct regions in boreal Quebec. We show that both hydrology and local water chemistry (mostly pH) interact to shape a sequential structuring of communities from highly diverse assemblages in headwater streams toward larger rivers and lakes dominated by fewer taxa. Increases in water residence time along the hydrologic continuum were accompanied by major losses of bacterial richness and by an increased differentiation of communities driven by local conditions (pH and other related variables). This suggests that hydrology and network position modulate the relative role of environmental sorting and mass effects on community assembly by determining both the time frame for bacterial growth and the composition of the immigrant pool. The apparent low dispersal limitation (that is, the lack of influence of geographic distance on the spatial patterns observed at the taxonomic resolution used) suggests that these boreal bacterioplankton communities derive from a shared bacterial pool that enters the networks through the smallest streams, largely dominated by mass effects, and that is increasingly subjected to local sorting of species during transit along the hydrologic continuum. PMID- 26849313 TI - Patterns and processes in microbial biogeography: do molecules and morphologies give the same answers? AB - Our knowledge on microbial biogeography depends on the way we define and study diversity. In contrast to most microbes, some protist lineages have conspicuous structures that allow comparisons of diversity concepts and measures-those based on molecules and those based on morphology. We analyzed a group of shell-bearing planktonic ciliates, the tintinnids, in a coast-to-ocean gradient using high throughput sequencing and microscopy. First, we compared molecular operational taxonomic units (OTUs) and morphospecies in terms of assemblage composition, distribution and relationships with the environment. OTUs revealed potentially novel and rare taxa, while morphospecies showed clearer correlations with environmental factors, and both approaches coincided in supporting a coastal versus oceanic pattern. Second, we explored which processes influence assembly across the environmental gradient examined. Assemblage fluctuations were associated with significant distance-decay and changes in morphospecies size and prey proxies, thus suggesting niche partitioning as a key structuring mechanism. Our conclusion is that molecules and morphologies generally agreed, but they provided complementary data, the first revealing hidden diversity, and the latter making better connections between distribution patterns and ecological processes. This highlights the importance of linking genotypes and phenotypes (using multidisciplinary analyses and/or reliable databases of barcoded species), to understand the diversity, biogeography and ecological roles of microbes. PMID- 26849315 TI - Microbial interactions with naturally occurring hydrophobic sediments: Influence on sediment and associated contaminant mobility. AB - The erosion, transport and fate of sediments and associated contaminants are known to be influenced by both particle characteristics and the flow dynamics imparted onto the sediment. The influential role of bitumen containing hydrophobic sediments and the microbial community on sediment dynamics are however less understood. This study links an experimental evaluation of sediment erosion with measured sediment-associated contaminant concentrations and microbial community analysis to provide an estimate of the potential for sediment to control the erosion, transport and fate of contaminants. Specifically the paper addresses the unique behaviour of hydrophobic sediments and the role that the microbial community associated with hydrophobic sediment may play in the transport of contaminated sediment. Results demonstrate that the hydrophobic cohesive sediment demonstrates unique transport and particle characteristics (poor settling and small floc size). Biofilms were observed to increase with consolidation/biostabilization times and generated a unique microbial consortium relative to the eroded flocs. Natural oil associated with the flocs appeared to be preferentially associated with microbial derived extracellular polymeric substances. While PAHs and naphthenic acid increased with increasing shear (indicative of increasing loads), they tended to decrease with consolidation/biostabilization (CB) time at similar shears suggesting a chemical and/or biological degradation. PAH and napthenic acid degrading microbes decreased with time as well, which may suggest that there was a reduced pool of PAHs and naphthenic acids available resulting in their die off. This study emphasizes the importance that any management strategies and operational assessments for the protection of human and aquatic health incorporate the sediment (suspended and bed sediment) and biological (biofilm) compartments and the energy dynamics within the system in order to better predict contaminant transport. PMID- 26849314 TI - The evolutionary dynamics of integrons in changing environments. AB - Integrons are genetic elements that are common in bacteria and are hotspots for genome evolution. They facilitate the acquisition and reassembly of gene cassettes encoding a variety of functions, including drug resistance. Despite their importance in clinical settings, the selective forces responsible for the evolution and maintenance of integrons are poorly understood. We present a mathematical model of integron evolution within bacterial populations subject to fluctuating antibiotic exposures. Bacteria carrying a functional integrase that mediates reshuffling of cassette genes and thereby modulates gene expression patterns compete with bacteria without a functional integrase. Our results indicate that for a wide range of parameters, the functional integrase can be stably maintained in the population despite substantial fitness costs. This selective advantage arises because gene-cassette shuffling generates genetic diversity, thus enabling the population to respond rapidly to changing selective pressures. We also show that horizontal gene transfer promotes stable maintenance of the integrase and can also lead to de novo assembly of integrons. Our model generates testable predictions for integron evolution, including loss of functional integrases in stable environments and selection for intermediate gene shuffling rates in changing environments. Our results highlight the need for experimental studies of integron population biology. PMID- 26849316 TI - Combination of granular activated carbon adsorption and deep-bed filtration as a single advanced wastewater treatment step for organic micropollutant and phosphorus removal. AB - Adsorption onto granular activated carbon (GAC) is an established technology in water and advanced wastewater treatment for the removal of organic substances from the liquid phase. Besides adsorption, the removal of particulate matter by filtration and biodegradation of organic substances in GAC contactors has frequently been reported. The application of GAC as both adsorbent for organic micropollutant (OMP) removal and filter medium for solids retention in tertiary wastewater filtration represents an energy- and space saving option, but has rarely been considered because high dissolved organic carbon (DOC) and suspended solids concentrations in the influent of the GAC adsorber put a significant burden on this integrated treatment step and might result in frequent backwashing and unsatisfactory filtration efficiency. This pilot-scale study investigates the combination of GAC adsorption and deep-bed filtration with coagulation as a single advanced treatment step for simultaneous removal of OMPs and phosphorus from secondary effluent. GAC was assessed as upper filter layer in dual-media downflow filtration and as mono-media upflow filter with regard to filtration performance and OMP removal. Both filtration concepts effectively removed suspended solids and phosphorus, achieving effluent concentrations of 0.1 mg/L TP and 1 mg/L TSS, respectively. Analysis of grain size distribution and head loss within the filter bed showed that considerable head loss occurred in the topmost filter layer in downflow filtration, indicating that most particles do not penetrate deeply into the filter bed. Upflow filtration exhibited substantially lower head loss and effective utilization of the whole filter bed. Well-adsorbing OMPs (e.g. benzotriazole, carbamazepine) were removed by >80% up to throughputs of 8000-10,000 bed volumes (BV), whereas weakly to medium adsorbing OMPs (e.g. primidone, sulfamethoxazole) showed removals <80% at <5,000 BV. In addition, breakthrough behavior was also determined for gabapentin, an anticonvulsant drug recently detected in drinking water resources for which suitable removal technologies are still largely unknown. Gabapentin showed poor adsorptive removal, resulting in rapid concentration increases. Whereas previous studies classified gabapentin as not readily biodegradable, sustained removal was observed after prolonged operation and points at biological elimination of gabapentin within the GAC filter. The application of GAC as filter medium was compared to direct addition of powdered activated carbon (PAC) to deep-bed filtration as a direct process alternative. Both options yielded comparable OMP removals for most compounds at similar carbon usage rates, but GAC achieved considerably higher removals for biodegradable OMPs. Based on the results, the application of GAC in combination with coagulation/filtration represents a promising alternative to powdered activated carbon and ozone for advanced wastewater treatment. PMID- 26849317 TI - Catalytic ozonation of organic pollutants from bio-treated dyeing and finishing wastewater using recycled waste iron shavings as a catalyst: Removal and pathways. AB - Catalytic ozonation of organic pollutants from actual bio-treated dyeing and finishing wastewater (BDFW) with iron shavings was investigated. Catalytic ozonation effectively removed organic pollutants at initial pH values of 7.18 7.52, and the chemical oxygen demand (COD) level decreased from 142 to 70 mg.L( 1) with a discharge limitation of 80 mg.L(-1). A total of 100% and 42% of the proteins and polysaccharides, respectively, were removed with a decrease in their contribution to the soluble COD from 76% to 41%. Among the 218 organic species detected by liquid chromatography-mass spectrometry, 58, 77, 79 and 4 species were completely removed, partially removed, increased and newly generated, respectively. Species including textile auxiliaries and dye intermediates were detected by gas chromatography-mass spectrometry. The inhibitory effect decreased from 51% to 33%, suggesting a reduction in the acute toxicity. The enhanced effect was due to hydroxyl radical (OH) oxidation, co-precipitation and oxidation by other oxidants. The proteins were removed by OH oxidation (6%), by direct ozonation, co-precipitation and oxidation by other oxidants (94%). The corresponding values for polysaccharides were 21% and 21%, respectively. In addition, the iron shavings behaved well in successive runs. These results indicated that the process was favorable for engineering applications for removal of organic pollutants from BDFW. PMID- 26849318 TI - Sensory Profiles and Seasonal Variation of Black Walnut Cultivars. AB - Black walnut (Juglans nigra L.) is a North American hardwood tree valued for producing nuts and wood. Black walnut cultivars were evaluated by a trained panel over 2 growing seasons to determine the seasonal variation in the sensory profile. Results showed that cultivars were significantly different on 3 appearance (skin color, nutmeat color, and kernel roughness), 1 aroma (black walnut ID), 5 flavor (black walnut ID, banana-like, piny, rancid, and overall nutty), and 2 texture attributes (surface roughness and hardness). These profiles were compared to results collected in 2011 to determine differences between growing seasons. Results showed 4 flavor attributes (black walnut ID, overall nutty, fruity-dark and rancid) had an interaction effect of year and cultivar, while 6 attributes (brown, caramelized, floral/fruity, piny, musty/dusty, and oily) showed a main effect of year. In general, flavor attributes had higher intensities in 2011 than in 2013. These results suggest that seasonal variation may influence flavor profile more than cultivar. Thus, using samples from only 1 growing season when testing agricultural products may not provide adequate information for the long term. PMID- 26849319 TI - Spatial and temporal variability of snow chemical composition and accumulation rate at Talos Dome site (East Antarctica). AB - Five snow pits and five firn cores were sampled during the 2003-2004 Italian Antarctic Campaign at Talos Dome (East Antarctica), where a deep ice core (TALDICE, TALos Dome Ice CorE, 1650m depth) was drilled in 2005-2008 and analyzed for ionic content. Particular attention is spent in applying decontamination procedures to the firn cores, as core sections were stored for approximately 10years before analysis. By considering the snow pit samples to be unperturbed, the comparison with firn core samples from the same location shows that ammonium, nitrate and MSA are affected by storage post-depositional losses. All the other measured ions are confirmed to be irreversibly deposited in the snow layer. The removal of the most external layers (few centimeters) from the firn core sections is proved to be an effective decontamination procedure. High-resolution profiles of seasonal markers (nitrate, sulfate and MSA) allow a reliable stratigraphic dating and a seasonal characterization of the samples. The calculated mean accumulation-rate values range from 70 to 85mmw.e.year(-1), in the period 2003 1973 with small differences between two sectors: 70-74mmw.e.year(-1) in the NNE sector (spanning 2003-1996years) and 81-92mmw.e.year(-1) in the SSW sector (spanning 2003-1980years). This evidence is interpreted as a coupled effect of wind-driven redistribution processes in accumulation/ablation areas. Statistical treatment applied to the concentration values of the snow pits and firn cores samples collected in different points reveals a larger temporal variability than spatial one both in terms of concentration of chemical markers and annual accumulation. The low spatial variability of the accumulation rate and chemical composition measured in the five sites demonstrates that the TALDICE ice core paleo-environmental and paleo-climatic stratigraphies can be considered as reliably representative for the Talos Dome area. PMID- 26849320 TI - Hydrogeomorphic connectivity on roads crossing in rural headwaters and its effect on stream dynamics. AB - Unpaved roads are ubiquitous features that have been transforming the landscape through human history. Unpaved roads affect the water and sediment pathways through a catchment and impacts the aquatic ecosystem. In this study, we describe the effect of unpaved road on the hydrogeomorphic connectivity at the rural headwater scale. Measurement was based on the stream crossing approach, i.e., road superimposing the drainage system. We installed a Parshall flume coupled with single-stage suspended sediment sampler at each stream crossing. In addition, we displayed our monitoring scheme with an upscaling perspective from second-order to third-order stream. We concluded that the road-stream coupling dramatically changed the stream dynamic. The increase of discharge caused by roads at the headwater was 50% larger compared to unaffected streams. Additionally, suspended sediment concentration enhancement at stream crossings ranged from to 413% at second-order streams to 145% at third-order streams. The landform characteristics associated with the road network produced an important hydrogeomorphic disruption in the landscape. As a result, the sediment filter function of the riparian zone was reduced dramatically. Therefore, we recommend that projects for aquatic system restoration or conservation in rural landscape consider the role of the road network on stream dynamics. PMID- 26849321 TI - A-Differential Synthetic Aperture Radar Interferometry analysis of a Deep Seated Gravitational Slope Deformation occurring at Bisaccia (Italy). AB - This paper presents the results of an investigation on a Deep Seated Gravitational Slope Deformation (DSGSD), previously only hypothesized by some authors, affecting Bisaccia, a small town located in Campania region, Italy. The study was conducted through the integration of conventional methods (geological geomorphological field survey, air-photo interpretation) and an Advanced Differential Interferometry Synthetic Aperture Radar (A-DInSAR) technique. The DSGSD involves a brittle lithotype (conglomerates of the Ariano Irpino Supersynthem) resting over a Structurally Complex Formation (Varycoloured Clays of Calaggio Formation). At Bisaccia, probably as a consequence of post-cyclic recompression phenomena triggered by reiterated seismic actions, the rigid plate made up of conglomeratic sediments resulted to be split in five portions, showing different rates of displacements, whose deformations are in the order of some centimeter/year, thus inducing severe damage to the urban settlement. A-DInSAR techniques confirmed to be a reliable tool in monitoring slow-moving landslides. In this case 96 ENVIronmental SATellite-Advanced Synthetic Aperture Radar (ENVISAT-ASAR) images, in ascending and descending orbits, have been processed using SUBSOFT software, developed by the Remote Sensing Laboratory (RSLab) group from the Universitat Politecnica de Catalunya (UPC). The DInSAR results, coupled with field survey, supported the analysis of the instability mechanism and confirmed the historical record of the movements already available for the town. PMID- 26849322 TI - A multi-stakeholder framework for urban runoff quality management: Application of social choice and bargaining techniques. AB - In this paper, an integrated framework is proposed for urban runoff management. To control and improve runoff quality and quantity, Low Impact Development (LID) practices are utilized. In order to determine the LIDs' areas and locations, the Non-dominated Sorting Genetic Algorithm-II (NSGA-II), which considers three objective functions of minimizing runoff volume, runoff pollution and implementation cost of LIDs, is utilized. In this framework, the Storm Water Management Model (SWMM) is used for stream flow simulation. The non-dominated solutions provided by the NSGA-II are considered as management scenarios. To select the most preferred scenario, interactions among the main stakeholders in the study area with conflicting utilities are incorporated by utilizing bargaining models including a non-cooperative game, Nash model and social choice procedures of Borda count and approval voting. Moreover, a new social choice procedure, named pairwise voting method, is proposed and applied. Based on each conflict resolution approach, a scenario is identified as the ideal solution providing the LIDs' areas, locations and implementation cost. The proposed framework is applied for urban water quality and quantity management in the northern part of Tehran metropolitan city, Iran. Results show that the proposed pairwise voting method tends to select a scenario with a higher percentage of reduction in TSS (Total Suspended Solid) load and runoff volume, in comparison with the Borda count and approval voting methods. Besides, the Nash method presents a management scenario with the highest cost for LIDs' implementation and the maximum values for percentage of runoff volume reduction and TSS removal. The results also signify that selection of an appropriate management scenario by stakeholders in the study area depends on the available financial resources and the relative importance of runoff quality improvement in comparison with reducing the runoff volume. PMID- 26849324 TI - SWAT-CS(enm): Enhancing SWAT nitrate module for a Canadian Shield catchment. AB - Nonpoint source modeling using hydrological models has been extensively studied at agriculture and urban watersheds; however, this has not been well addressed in forested ones where agricultural sources are comparatively minimal and nitrogen deposition exerts remarkable impacts on the nutrient cycles of a catchment. Thus it is critically important for hydrological models to incorporate the dynamics of nitrogen deposition and its transport processes, for reasonable nitrogen modeling. This is especially so for the Canadian Shield, which is characterized by a cold climate and special physiographic features. A revision of Soil and Water Assessment Tool for Canadian Shield (SWAT-CS) was proposed by Fu et al. (2014) to better characterize the hydrological features. In this study, more revisions were added to better simulate processes of nitrate by: 1) incorporating the dynamics of nitrogen deposition; and 2) allowing the deposition to distribute along with rapid-moving macropore flows. The newly revised model, SWAT-CS(enm) (SWAT-CS with an Enhanced Nitrate Module), and SWAT-CS were calibrated and tested with data of a subbasin of Harp Lake in south-central Ontario for 1990 to 2007. Modeling performance of nitrate flux rate in the stream for SWAT-CS(enm) was nearly acceptable with maximum daily Nash-Sutcliffe efficiencies (ENSs) for calibration and validation periods of 0.66 and 0.43, respectively; whereas the result of SWAT-CS was generally unsatisfied with maximum daily ENSs of 0.16 and 0.07, respectively. An uncertainty analysis using GLUE (generalized likelihood uncertainty estimation) showed a modest performance as about 50% of observations can be incorporated by the 95% prediction range deriving from the behavioral solutions (ENS>=0.5) for both daily and monthly simulations. It is concluded that the enhanced nitrate module improved the model performance of SWAT-CS on nitrate modeling, since the previous SWAT-CS failed to consider the effect of dynamics of nitrogen deposition and its sequential processes at the investigated site. PMID- 26849323 TI - Variation in predicted internal concentrations in relation to PBPK model complexity for rainbow trout. AB - The present study is motivated by the increasing demand to consider internal partitioning into tissues instead of exposure concentrations for the environmental toxicity assessment. To this end, physiologically based pharmacokinetic (PBPK) models can be applied. We evaluated the variation in accuracy of PBPK model outcomes depending on tissue constituents modeled as sorptive phases and chemical distribution tendencies addressed by molecular descriptors. The model performance was examined using data from 150 experiments for 28 chemicals collected from US EPA databases. The simplest PBPK model is based on the "Kow-lipid content" approach as being traditional for environmental toxicology. The most elaborated one considers five biological sorptive phases (polar and non-polar lipids, water, albumin and the remaining proteins) and makes use of LSER (linear solvation energy relationship) parameters to describe the compound partitioning behavior. The "Kow-lipid content"-based PBPK model shows more than one order of magnitude difference in predicted and measured values for 37% of the studied exposure experiments while for the most elaborated model this happens only for 7%. It is shown that further improvements could be achieved by introducing corrections for metabolic biotransformation and compound transmission hindrance through a cellular membrane. The analysis of the interface distribution tendencies shows that polar tissue constituents, namely water, polar lipids and proteins, play an important role in the accumulation behavior of polar compounds with H-bond donating functional groups. For compounds without H-bond donating fragments preferable accumulation phases are storage lipids and water depending on compound polarity. PMID- 26849325 TI - Surface tailored organobentonite enhances bacterial proliferation and phenanthrene biodegradation under cadmium co-contamination. AB - Co-contamination of soil and water with polycyclic aromatic hydrocarbon (PAH) and heavy metals makes biodegradation of the former extremely challenging. Modified clay-modulated microbial degradation provides a novel insight in addressing this issue. This study was conducted to evaluate the growth and phenanthrene degradation performance of Mycobacterium gilvum VF1 in the presence of a palmitic acid (PA)-grafted Arquad(r) 2HT-75-based organobentonite in cadmium (Cd) phenanthrene co-contaminated water. The PA-grafted organobentonite (ABP) adsorbed a slightly greater quantity of Cd than bentonite at up to 30mgL(-1) metal concentration, but its highly negative surface charge imparted by carboxylic groups indicated the potential of being a significantly superior adsorbent of Cd at higher metal concentrations. In systems co-contained with Cd (5 and 10mgL( 1)), the Arquad(r) 2HT-75-modified bentonite (AB) and PA-grafted organobentonite (ABP) resulted in a significantly higher (72-78%) degradation of phenanthrene than bentonite (62%) by the bacterium. The growth and proliferation of bacteria were supported by ABP which not only eliminated Cd toxicity through adsorption but also created a congenial microenvironment for bacterial survival. The macromolecules produced during ABP-bacteria interaction could form a stable clay bacterial cluster by overcoming the electrostatic repulsion among individual components. Findings of this study provide new insights for designing clay modulated PAH bioremediation technologies in mixed-contaminated water and soil. PMID- 26849326 TI - Genotoxic and cytotoxic effects of ZnO nanoparticles for Dunaliella tertiolecta and comparison with SiO2 and TiO2 effects at population growth inhibition levels. AB - The increasing use of oxide nanoparticles (NPs) in commercial products has intensified the potential release into the aquatic environment where algae represent the basis of the trophic chain. NP effects upon algae population growth were indeed already reported in literature, but the concurrent effects at cellular and genomic levels are still largely unexplored. Our work investigates the genotoxic (by COMET assay) and cytotoxic effects (by qualitative ROS production and cell viability) of ZnO nanoparticles toward marine microalgae Dunaliella tertiolecta. A comparison at defined population growth inhibition levels (i.e. 50% Effect Concentration, EC50, and No Observed Effect Concentration, NOEC) with SiO2 and TiO2 genotoxic effects and previously investigated cytotoxic effects (Manzo et al., 2015) was performed in order to elucidate the possible diverse mechanisms leading to algae growth inhibition. After 72h exposure, ZnO particles act firstly at the level of cell division inhibition (EC50: 2mg Zn/L) while the genotoxic action is evident only starting from 5mg Zn/L. This outcome could be ascribable mainly to the release of toxic ions from the aggregate of ZnO particle in the proximity of cell membrane. In the main, at EC50 and NOEC values for ZnO NPs showed the lowest cytotoxic and genotoxic effect with respect to TiO2 and SiO2. Based on Mutagenic Index (MI) the rank of toxicity is actually: TiO2>SiO2>ZnO with TiO2 and SiO2 that showed similar MI values at both NOEC and EC50 concentrations. The results presented herein suggest that up to TiO2 NOEC (7.5mg/L), the algae DNA repair mechanism is efficient and the DNA damage does not result in an evident algae population growth inhibition. A similar trend for SiO2, although at lower effect level with respect to TiO2, is observable. The comparison among all the tested nanomaterial toxicity patterns highlighted that the algae population growth inhibition occurred through pathways specific for each NP also related to their different physicochemical behaviors in seawater. PMID- 26849327 TI - Inorganic pollution around the Qinghai-Tibet Plateau: An overview of the current observations. AB - The Qinghai-Tibet Plateau is the highest geographical unit in the world. Thus, it serves an important role in evaluating long-term ecologic conditions and environmental status and changes over time. This study summarizes major and trace element concentrations in biota and in water and soil. It also pays attention to gaseous pollutant and particle concentrations in air around the Qinghai-Tibet Plateau. The degree of soil heavy metal contamination and the water heavy metal hazard index were respectively evaluated. The contamination degrees of two sampling areas around the Qinghai-Tibet Plateau reached extremely high levels with soil mCd (modified degree of contamination) values exceeding 20. Surprisingly, over 54% of sampling areas showed moderate or more serious soil contamination degree (mCd>1.5). Moreover, the hazard indexes of two important rivers were 1.56 and 7.59, reaching unacceptable level. The potential risk might be beyond our expectation. Therefore, it should be an urgent and top priority to identify and confirm possible pollution sources around the Qinghai-Tibet Plateau. Then, it is imperative to implement feasible and effective environmental quality control strategies. PMID- 26849328 TI - Dissipation and effects of tricyclazole on soil microbial communities and rice growth as affected by amendment with alperujo compost. AB - The presence of pesticides in surface and groundwater has grown considerably in the last decades as a consequence of the intensive farming activity. Several studies have shown the benefits of using organic amendments to prevent losses of pesticides from runoff or leaching. A particular soil from the Guadalquivir valley was placed in open air ponds and amended at 1 or 2% (w/w) with alperujo compost (AC), a byproduct from the olive oil industry. Tricyclazole dissipation, rice growth and microbial diversity were monitored along an entire rice growing season. An increase in the net photosynthetic rate of Oryza sativa plants grown in the ponds with AC was observed. These plants produced between 1100 and 1300kgha(-1) more rice than plants from the unamended ponds. No significant differences were observed in tricyclazole dissipation, monitored for a month in soil, surface and drainage water, between the amended and unamended ponds. The structure and diversity of bacteria and fungi communities were also studied by the use of the polymerase chain reaction denaturing gel electrophoresis (PCR DGGE) from DNA extracted directly from soil samples. The banding pattern was similar for all treatments, although the density of bands varied throughout the time. Apparently, tricyclazole did not affect the structure and diversity of bacteria and fungi communities, and this was attributed to its low bioavailability. Rice cultivation under paddy field conditions may be more efficient under the effects of this compost, due to its positive effects on soil properties, rice yield, and soil microbial diversity. PMID- 26849329 TI - Carbon cycling and exports over diel and flood-recovery timescales in a subtropical rainforest headwater stream. AB - Catchment headwaters comprise the majority of all stream length globally, however, carbon (C) dynamics in these systems remains poorly understood. We combined continuous measurements of pCO2 and radon ((222)Rn, a natural groundwater tracer) with discrete sampling for particulate organic, dissolved organic and inorganic carbon (POC, DOC, and DIC) to assess the short-term carbon dynamics of a pristine subtropical headwater stream in Australia, over contrasting hydrologic regimes of drought, flash-flooding and recovery. Observations over 23days revealed a shift from carbon losses dominated by CO2 outgassing under conditions of low flow (66.4+/-0.4% of carbon export) to downstream exports of carbon during the flood (87.8+/-9.7% of carbon export). DOC was the dominant form of downstream exports throughout the study (DOC:DIC:POC=0.82:0.05:0.13). The broadest diel variability among variables occurred during the drought phase, with diel variability up to 662MUatmd(-1) (or 27MUM[CO2*]d(-1)), 17MUMd(-1) and 268Bqm(-3)d(-1) for pCO2, dissolved oxygen and (222)Rn, respectively. Diel dynamics indicated multiple interrelated drivers of stream water chemistry including groundwater seepage and in-stream metabolism. The catchment exported terrestrial carbon throughout the field campaign, with a mean net stream flux of 4.7+/-7.8mmolCm(-2)(catchment area)d(-1) which is equivalent to 1.4+/-2.3% of the estimated local terrestrial net primary production. Our observations highlight the importance of accounting for hydrological extremes when assessing the carbon budgets and ecosystem metabolism of headwater streams, and provide a first estimate of aquatic carbon exports from a pristine Australian subtropical rainforest. PMID- 26849330 TI - Characterization and mobility of arsenic and heavy metals in soils polluted by the destruction of arsenic-containing shells from the Great War. AB - Destruction of chemical munitions from World War I has caused extensive local top soil contamination by arsenic and heavy metals. The biogeochemical behavior of toxic elements is poorly documented in this type of environment. Four soils were sampled presenting different levels of contamination. The range of As concentrations in the samples was 1937-72,820mg/kg. Concentrations of Zn, Cu and Pb reached 90,190mg/kg, 9113mg/kg and 5777mg/kg, respectively. The high clay content of the subsoil and large amounts of charcoal from the use of firewood during the burning process constitute an ample reservoir of metals and As-binding materials. However, SEM-EDS observations showed different forms of association for metals and As. In metal-rich grains, several phases were identified: crystalline phases, where arsenate secondary minerals were detected, and an amorphous phase rich in Fe, Zn, Cu, and As. The secondary arsenate minerals, identified by XRD, were adamite and olivenite (zinc and copper arsenates, respectively) and two pharmacosiderites. The amorphous material was the principal carrier of As and metals in the central part of the site. This singular mineral assemblage probably resulted from the heat treatment of arsenic-containing shells. Microbial characterization included total cell counts, respiration, and determination of As(III)-oxidizing activities. Results showed the presence of microorganisms actively contributing to metabolism of carbon and arsenic, even in the most polluted soil, thereby influencing the fate of bioavailable As on the site. However, the mobility of As correlated mainly with the availability of iron sinks. PMID- 26849331 TI - Biostimulation of metal-resistant microbial consortium to remove zinc from contaminated environments. AB - Understanding the diversity and metal removal ability of microorganisms associated to contaminated aquatic environments is essential to develop metal remediation technologies in engineered environments. This study investigates through 16S rRNA deep sequencing the composition of a biostimulated microbial consortium obtained from the polluted Tiete River in Sao Paulo, Brazil. The bacterial diversity of the biostimulated consortium obtained from the contaminated water and sediment was compared to the original sample. The results of the comparative sequencing analyses showed that the biostimulated consortium and the natural environment had gamma-Proteobacteria, Firmicutes, and uncultured bacteria as the major classes of microorganisms. The consortium optimum zinc removal capacity, evaluated in batch experiments, was achieved at pH=5 with equilibrium contact time of 120min, and a higher Zn-biomass affinity (KF=1.81) than most pure cultures previously investigated. Analysis of the functional groups found in the consortium demonstrated that amine, carboxyl, hydroxyl, and phosphate groups present in the consortium cells were responsible for zinc uptake. PMID- 26849332 TI - A new approach to nationwide sanitation planning for developing countries: Case study of Indonesia. AB - Many developing countries struggle to provide wastewater and solid waste services. The backlog in access has been partly attributed to the absence of a functional sanitation planning framework. Various planning tools are available; however a comprehensive framework that directly links a government policy to nationwide planning is missing. Therefore, we propose a framework to facilitate the nationwide planning process for the implementation of wastewater and solid waste services. The framework requires inputs from government planners and experts in the formulation of starting points and targets. Based on a limited number of indicators (population density, urban functions) three outputs are generated. The first output is a visualization of the spatial distribution of wastewater and solid waste systems to support regional priority setting in planning and create awareness. Secondly, the total number of people served, budget requirements and distribution of systems is determined. Thirdly, the required budget is allocated to the responsible institution to assure effective implementation. The determined budgets are specified by their beneficiaries, distinguishing urban, rural, poor and non-poor households. The framework was applied for Indonesia and outputs were adopted in the National Development Plan. The required budget to reach the Indonesian government's 2019 target was determined to be 25 billion US$ over 5years. The contribution from the national budget required a more than fivefold increase compared to the current budget allocation in Indonesia, corresponding to an increase from 0.5 to 2.7 billion US$ per year. The budget for campaigning, advocacy and institutional strengthening to enable implementation was determined to be 10% of the total budget. The proposed framework is not only suitable for Indonesia, but could also be applied to any developing country that aims to increase access to wastewater and solid waste facilities. PMID- 26849334 TI - First measurements of ambient aerosol over an ecologically sensitive zone in Central India: Relationships between PM2.5 mass, its optical properties, and meteorology. AB - PM2.5 mass and its optical properties were measured over an ecologically sensitive zone in Central India between January and December, 2012. Meteorological parameters including temperature, relative humidity, wind speed, wind direction, and barometric pressure were also monitored. During the study period, the PM2.5 (fine PM) concentration ranged between 3.2MUgm(-3) and 193.9MUgm(-3) with a median concentration of 31.4MUgm(-3). The attenuation coefficients, betaATN at 370nm, 550nm, and 880nm had median values of 104.5Mm( 1), 79.2Mm(-1), and 59.8Mm(-1), respectively. Further, the dry scattering coefficient, betaSCAT at 550nm had a median value of 17.1Mm(-1) while the absorption coefficient betaABS at 550nm had a median value of 61.2Mm(-1). The relationship between fine PM mass and attenuation coefficients showed pronounced seasonality. Scattering, absorption, and attenuation coefficient at different wavelengths were all well correlated with fine PM mass only during the post monsoon season (October, November, and December). The highest correlation (r(2)=0.81) was between fine PM mass and betaSCAT at 550nm during post-monsoon season. During this season, the mass scattering efficiency (sigmaSCAT) was 1.44m(2)g(-1). Thus, monitoring optical properties all year round, as a surrogate for fine PM mass was found unsuitable for the study location. In order to assess the relationships between fine PM mass and its optical properties and meteorological parameters, multiple linear regression (MLR) models were fitted for each season, with fine PM mass as the dependent variable. Such a model fitted for the post-monsoon season explained over 88% of the variability in fine PM mass. However, the MLR models were able to explain only 31 and 32% of the variability in fine PM during pre-monsoon (March, April, and May) and monsoon (June, July, August, and September) seasons, respectively. During the winter (January and February) season, the MLR model explained 54% of the PM2.5 variability. PMID- 26849333 TI - Plastic mulching in agriculture. Trading short-term agronomic benefits for long term soil degradation? AB - Plastic mulching has become a globally applied agricultural practice for its instant economic benefits such as higher yields, earlier harvests, improved fruit quality and increased water-use efficiency. However, knowledge of the sustainability of plastic mulching remains vague in terms of both an environmental and agronomic perspective. This review critically discusses the current understanding of the environmental impact of plastic mulch use by linking knowledge of agricultural benefits and research on the life cycle of plastic mulches with direct and indirect implications for long-term soil quality and ecosystem services. Adverse effects may arise from plastic additives, enhanced pesticide runoff and plastic residues likely to fragment into microplastics but remaining chemically intact and accumulating in soil where they can successively sorb agrochemicals. The quantification of microplastics in soil remains challenging due to the lack of appropriate analytical techniques. The cost and effort of recovering and recycling used mulching films may offset the aforementioned benefits in the long term. However, comparative and long-term agronomic assessments have not yet been conducted. Furthermore, plastic mulches have the potential to alter soil quality by shifting the edaphic biocoenosis (e.g. towards mycotoxigenic fungi), accelerate C/N metabolism eventually depleting soil organic matter stocks, increase soil water repellency and favour the release of greenhouse gases. A substantial process understanding of the interactions between the soil microclimate, water supply and biological activity under plastic mulches is still lacking but required to estimate potential risks for long-term soil quality. Currently, farmers mostly base their decision to apply plastic mulches rather on expected short-term benefits than on the consideration of long-term consequences. Future interdisciplinary research should therefore gain a deeper understanding of the incentives for farmers and public perception from both a psychological and economic perspective in order to develop new support strategies for the transition into a more environment-friendly food production. PMID- 26849335 TI - Cotransport of graphene oxide and Cu(II) through saturated porous media. AB - This study examines the cotransport of graphene oxide (GO) and Cu in porous media. The impacts of GO concentration and ion strength (IS) on Cu transport in laboratory packed columns were investigated. The results indicated that GO had fairly high mobility at a IS of 1mM, and could serve as an effective carrier of Cu(II). The facilitated transport was found to increase with increasing concentration of GO (CGO). The peak effluent concentration (C/C0)max of Cu was 0.57 at CGO of 120mg/L and IS=1mM and 0.13 at 40mg/L and IS=1mM. The Cu appears to be irreversibly adsorbed by the sand because no Cu appeared in the effluent in the absence of GO. However, the GO-facilitated Cu transport was reduced as the IS increased from 1 to 1000mM. In fact, the facilitated transport was zero percent at an IS of 1000mM. Particle size analysis, Zeta potential measurements and DLVO calculations demonstrated that higher IS values made the GO became unstable and it flocculated and attached to the sand. We also fed GO into the column pre equilibrated by Cu as sequential elution experiments and found that the later introduced GO can complex the pre-adsorbed Cu from the sand surface because GO has a higher adsorption affinity for Cu. An advection-dispersion-retention numerical model was able to describe the Cu and GO transport in the column. Our work provides useful insights into fate, transport and risk assessment of heavy metal contaminants in the presence of engineered nanoparticles. PMID- 26849336 TI - Indoor/outdoor PM2.5 elemental composition and organic fraction medications, in a Greek hospital. AB - In the newly constructed General Hospital of Kavala, Greece, air quality was monitored in two indoor locations (the Triage room at the emergency department and the Laboratory of bio-pathology) and also outdoors. Indoor PM2.5 filter samples were collected at both rooms and outdoors, in the yard of the hospital. PM2.5 organic content and elemental composition were determined. Analyses of selected organic compounds in PM2.5 samples, revealed that chemicals from medications were distributed in the air of the hospital. Qualitatively, dehydrocholic acid, hydrocortisone acetate, gama-bufotalin, syrosingopine, dimethyl phthalate and o,p'-DDT were found in the Triage. In the bio-pathology laboratory, triethoxypentylsilane and carbohydrazide were also found. An unexpected air pollutant pathway was the pneumatic system which delivered the blood samples from the emergency department to the bio-pathology laboratory, as the presence of gama-bufotalin and syrosingopine was found in the aerosol samples from both locations. Indoor PM2.5 24-h average mass concentration ranged from 10.16MUgm(-3) to 21.87MUgm(-3) in the laboratory and between 9.86MUgm(-3) to 26.27MUgm(-3) in the Triage room, where the limit value set for human health protection, i.e. 25MUgm(-3) for 24h, was exceeded once. The I/O 24-h average PM2.5 mass concentration ratio, ranged from 0.74-1.11 in the Triage and from 0.67 1.07 in the Lab, respectively. On the contrary, the I/O elemental concentration ratios were below unity for the whole campaign, indicating an outdoor origin of the monitored elements (Al, Si, Br, P, S, Na, K, Mg, Ca, Co, Cr, Cu, Fe, Mn, Ni, Pb, Ti and Zn). This finding was also confirmed by high sulfur I/O ratios in both rooms. The diurnal variations of PM2.5, Black Carbon, CO2 concentrations and microclimatic conditions were also monitored. PMID- 26849338 TI - Estimation of hydraulic parameters in a complex porous aquifer system using geoelectrical methods. AB - Geoelectrical methods have been widely used for the estimation of aquifer hydraulic properties. In this study, geoelectrical methods were applied in a lithologically and hydrochemically complex porous aquifer to estimate its porosity, hydraulic conductivity and transmissivity. For this purpose, the electrical resistivity of the aquifer as well as the electrical conductivity of the groundwater was measured in 37 sites and wells. Initially, the Archie's law was used to generate sets of cementation factor (m) and alpha (alpha) parameter from which the mode values of alpha=0.98 and m=1.75 are representative of the studied aquifer. The transmissivity of the aquifer varies from 5.1*10(-3) to 3.1*10(-5)m(2)/s, whereas the mean value of its porosity is 0.45. The hydraulic conductivity of the aquifer which was calculated according to Archie's law varies from 2.08*10(-6) to 6.84*10(-5)m/s and is strongly correlated with the pumping test's hydraulic conductivity. In contrast, the hydraulic conductivity which was calculated using Dar-Zarrouk parameters presents lower correlation with the pumping test's hydraulic conductivity. Furthermore, a relation between aquifer resistivity and hydraulic conductivity was established for the studied aquifer to enable the estimation of these parameters in sites lacking data. PMID- 26849337 TI - Modeling the pH-mediated extraction of ionizable organic contaminants to improve the quality of municipal sewage sludge destined for land application. AB - A model was developed to assess the impact of adding acids and bases to processed municipal sewage sludge (MSS) to mobilize contaminants, facilitating their removal from sludge by flushing prior to land application. Among 312 organic contaminants documented to occur in U.S. MSS, 71 or 23% were identified as ionizable organic contaminants (IOCs), contributing a disproportionately large fraction of 82% of the total mass of sludge-borne contaminants. Detected IOCs included 57 pharmaceuticals and personal care products, 12 perfluorinated compounds, one surfactant and one pesticide. Annually, about 2000t of IOCs were estimated to be released to U.S. soils via land-application of MSS. A partitioning model developed to assess the impact of pH on hydrophobic sorption revealed that between 36 and 85% of the mass of individual classes of IOCs potentially could be desorbed from MSS via pH adjustment and flushing. Thus, modeling results suggest that a sequential pH treatment [acidic (~pH2) followed by basic (~pH12) treatment] has the potential to reduce the burden of harmful IOCs in MSS applied on U.S. land by up to 40+/-16t annually. This approach may serve as a cost-effective treatment process that can be implemented easily in existing sludge treatment infrastructure in the U.S. and worldwide, serving to significantly improve the quality of MSS destined for land application. PMID- 26849339 TI - Ambient bioaerosol particle dynamics observed during haze and sunny days in Beijing. AB - The chemical characteristics of airborne particulate matter (PM) have been extensively studied; however, little information exists for its biological components (bioaerosol) especially during a haze event in mega cities. Herein, we studied the bioaerosol (fluorescent particle) dynamics on both haze and sunny days in Beijing from Dec. 2013 to March 2014 by employing a widely used real-time bioaerosol sensor-ultraviolet aerodynamic particle spectrometer (UV-APS). Firstly, we studied the fluorescent particle (BioPM) concentration and size distributions during three independent haze and three independent sunny days. Secondly, we investigated BioPM dynamics over a two-week long monitoring period which included consecutive haze days and alternated sunny days. In addition, we analyzed bacterial community structures and endotoxin levels in the air samples using pyrosequencing and Limulus amebocyte lysate (LAL) method, respectively. More than 6-fold higher fluorescent particle concentrations up to 5*10(5)/m(3) with peaks at night or early dawn were detected at the time of haze occurrences than those observed on sunny days. When the haze episode progressed for 3-5days, the BioPM concentrations were observed to decrease to the levels that were typically observed on sunny days. In general, ozone levels were found to be elevated at noon, while BioPM, NOx and relative humidity were reduced. Gene sequence analysis revealed no significant difference in abundances and community structures for top 13 bacterial genera between haze and sunny days, yet about twice higher endotoxin levels (12.4EU/m(3)) were detected on haze days than on sunny days. The results here facilitate a better understanding of atmospheric fluorescent particle dynamics including those under haze events. PMID- 26849340 TI - Influence of green waste compost on azimsulfuron dissipation and soil functions under oxic and anoxic conditions. AB - Concerns have been raised over the sustainability of intensive rice cultivation, where the use of chemical fertilizers and pesticides has been associated with numerous environmental problems. The objective of this study was to test the effect of the herbicide azimsulfuron on important soil functions as affected by amendment with a byproduct of the olive oil industry. Soil was collected from a Mediterranean rice field. Part of it was amended with alperujo compost (AC). Amended and unamended soils were incubated for 43days in presence or not of azimsulfuron, under anoxic-flooded (AF) and oxic-unflooded (OU) conditions. We monitored the dissipation of the herbicide azimsulfuron, C mineralization, soil microbial biomass (SMB) and dissolved organic carbon (DOC) content and its nature. Under AF conditions, the application of compost produced an increase in the dissipation of the herbicide (up to 12.4%). It was related with the higher DOC content, 4 times higher than under OU conditions. Though increases in carbon turnover (under AF and OU conditions) and reduction of SMBC after herbicide application (only under AF conditions) were observed, the differences were not statistically significant. The application of this organic amendment is presented as an efficient management strategy to increase C turnover in agricultural soils and reduce some of the negative effects derived from the application of azimsulfuron under flooded conditions. PMID- 26849341 TI - Quantitative evaluation of specific vulnerability to nitrate for groundwater resource protection based on process-based simulation model. AB - It has been proved that groundwater vulnerability assessment is an effective tool for groundwater protection. Nowadays, quantitative assessment methods for specific vulnerability are scarce due to limited cognition of complicated contaminant fate and transport processes in the groundwater system. In this paper, process-based simulation model for specific vulnerability to nitrate using 1D flow and solute transport model in the unsaturated vadose zone is presented for groundwater resource protection. For this case study in Jilin City of northeast China, rate constants of denitrification and nitrification as well as adsorption constants of ammonium and nitrate in the vadose zone were acquired by laboratory experiments. The transfer time at the groundwater table t50 was taken as the specific vulnerability indicator. Finally, overall vulnerability was assessed by establishing the relationship between groundwater net recharge, layer thickness and t50. The results suggested that the most vulnerable regions of Jilin City were mainly distributed in the floodplain of Songhua River and Mangniu River. The least vulnerable areas mostly appear in the second terrace and back of the first terrace. The overall area of low, relatively low and moderate vulnerability accounted for 76% of the study area, suggesting the relatively low possibility of suffering nitrate contamination. In addition, the sensitivity analysis showed that the most sensitive factors of specific vulnerability in the vadose zone included the groundwater net recharge rate, physical properties of soil medium and rate constants of nitrate denitrification. By validating the suitability of the process-based simulation model for specific vulnerability and comparing with index-based method by a group of integrated indicators, more realistic and accurate specific vulnerability mapping could be acquired by the process-based simulation model acquiring. In addition, the advantages, disadvantages, constraint conditions and applying prospects of the quantitative approach for specific vulnerability assessment were discussed. PMID- 26849342 TI - Urbanization and agriculture increase exports and differentially alter elemental stoichiometry of dissolved organic matter (DOM) from tropical catchments. AB - Many tropical biomes are threatened by rapid land-use change, but its catchment wide biogeochemical effects are poorly understood. The few previous studies on DOM in tropical catchments suggest that deforestation and subsequent land use increase stream water dissolved organic carbon (DOC) concentrations, but consistent effects on DOM elemental stoichiometry have not yet been reported. Here, we studied stream water DOC concentrations, catchment DOC exports, and DOM elemental stoichiometry in 20 tropical catchments at the Cerrado-Atlantic rainforest transition, dominated by natural vegetation, pasture, intensive agriculture, and urban land cover. Streams draining pasture could be distinguished from those draining natural catchments by their lower DOC concentrations, with lower DOM C:N and C:P ratios. Catchments with intensive agriculture had higher DOC exports and lower DOM C:P ratios than natural catchments. Finally, with the highest DOC concentrations and exports, as well as the highest DOM C:P and N:P ratios, but the lowest C:N ratios among all land-use types, urbanized catchments had the strongest effects on catchment DOM. Thus, urbanization may have alleviated N limitation of heterotrophic DOM decomposition, but increased P limitation. Land use-especially urbanization-also affected the seasonality of catchment biogeochemistry. While natural catchments exhibited high DOC exports and concentrations, with high DOM C:P ratios in the rainy season only, urbanized catchments had high values in these variables throughout the year. Our results suggest that urbanization and pastoral land use exerted the strongest impacts on DOM biogeochemistry in the investigated tropical catchments and should thus be important targets for management and mitigation efforts. PMID- 26849343 TI - Modeling surface energy fluxes and thermal dynamics of a seasonally ice-covered hydroelectric reservoir. AB - The thermal dynamics of human created northern reservoirs (e.g., water temperatures and ice cover dynamics) influence carbon processing and air-water gas exchange. Here, we developed a process-based one-dimensional model (Snow, Ice, WAater, and Sediment: SIWAS) to simulate a full year's surface energy fluxes and thermal dynamics for a moderately large (>500km(2)) boreal hydroelectric reservoir in northern Quebec, Canada. There is a lack of climate and weather data for most of the Canadian boreal so we designed SIWAS with a minimum of inputs and with a daily time step. The modeled surface energy fluxes were consistent with six years of observations from eddy covariance measurements taken in the middle of the reservoir. The simulated water temperature profiles agreed well with observations from over 100 sites across the reservoir. The model successfully captured the observed annual trend of ice cover timing, although the model overestimated the length of ice cover period (15days). Sensitivity analysis revealed that air temperature significantly affects the ice cover duration, water and sediment temperatures, but that dissolved organic carbon concentrations have little effect on the heat fluxes, and water and sediment temperatures. We conclude that the SIWAS model is capable of simulating surface energy fluxes and thermal dynamics for boreal reservoirs in regions where high temporal resolution climate data are not available. SIWAS is suitable for integration into biogeochemical models for simulating a reservoir's carbon cycle. PMID- 26849344 TI - Nutrient and metal pollution of the eastern Gulf of Finland coastline: Sediments, macroalgae, microbiota. AB - The anthropogenic pollution along the coastline of the eastern Gulf of Finland was studied through a range of methods, including analyses of metal contamination in water, surface sediments, accumulated algal biomass and its correlation with resistant microbiota. According to concentrations, the main pollutants in water were copper and manganese. Influence of Nuclear Power Plant was remarkable in adjacent areas and was expressed in high concentrations of molybdenum, nickel, copper and other elements in the water. Relatively high concentrations of copper, lead and zinc were found in sediments. Microbial tolerance appeared to be correlated with the concentration of the metals in sediments. Higher tolerance levels were found in sediment samples from more polluted stations. Macroalgae, which were massively developed in the coastal zone, had shown high level of metal bioaccumulation. Analyses of carbon, nitrogen and phosphorus content of algal tissues allowed the estimation of additional nutrient loading from accumulated decaying algal biomass on the coastal zone of the eastern Gulf of Finland. Mass development of algae in coastal area may contribute to accumulation of organic matter and associated metals. In our study the highest metal concentrations in sediments were found at the sites with dense and continuous layer of fresh and decaying macroalgal biomass, accompanied by hypoxic conditions. Also our study has shown that accumulated biomass may be a significant source of nutrients in the coastal ecosystem. PMID- 26849345 TI - Fluorescence labelling as tool for zeolite particle tracking in nanoremediation approaches. AB - Colloidal Fe-zeolites such as Fe-BEA-35 are currently under study as new adsorbent and catalyst materials for in-situ chemical oxidation with H2O2. As for nanoremediation in general, the availability of suitable particle detection methods is a requirement for successful process development and particle tracing. Detection and distinguishing between natural colloids and introduced particles with a similar composition are a challenge. By means of fluorescence labelling, a highly specific detection option for Fe-BEA-35 was developed. 'Ship-in-a-bottle' synthesis of fluorescein within the zeolite pores, which was applied for the first time for a BEA type zeolite, provides a product with stable and non extractable fluorescence. When the fluorescent labelled zeolite is added at a concentration of 1wt.% referring to the total zeolite mass, a very low detection limit of 1mg/L of total zeolite is obtained. Compared to commonly applied turbidity measurements, detection via fluorescence labelling is much more specific and sensitive. Fluorescence is only marginally affected by carboxymethyl cellulose, which is frequently applied as stabilizer in application suspensions but will be depleted upon contact with H2O2. Transport properties of fluorescent labelled and non-labelled Fe-zeolite particles are in agreement as determined in a column study with quartz sand and synthetic groundwater (classified as very hard). PMID- 26849346 TI - Chemical and biological assessment of endocrine disrupting chemicals in a full scale dairy manure anaerobic digester with thermal pretreatment. AB - Concentrated animal feeding operations are important sources of estrogens and their conjugates, which are introduced into the environment through manure land application. In this study, concentrations of estrogens were measured in an anaerobic co-digestion system with thermal pasteurization pretreatment. Free estrogens (estrone (E1), 17alpha-estradiol (E2alpha), 17beta-estradiol (E2beta), estriol (E3)) were analyzed by gas chromatography with mass spectrometry (GC/MS), and conjugated estrogens (sulfate- and glucuronide-conjugates) were analyzed by liquid chromatography with tandem mass spectrometry (LC/MS/MS). Additionally, yeast estrogen screen assay was used to determine the estrogenic potential of the manure. The total hormone concentrations (mainly E1, E2alpha, E2beta, and sulfated estrogens) were observed at concentrations up to a total of 7100ng/L in the liquid fraction, while free estrogen levels were 630ng/kg in the solid fraction of the untreated manure. The total hormone concentration did not decrease significantly during digestion, however, the relative composition of the estrogens changed from E2alpha (65%) being the predominant species before digestion to mostly E1 (72%) after digestion. This conversion process has important implications because E1 is more estrogenic than E2alpha. Total E2 equivalents associated with E1, E2alpha and E2beta concentrations as determined by GC/MS indicate that E1 is the most important contributor to the endocrine disruption activity of the treated manure. PMID- 26849348 TI - Ultrasensitive electrochemical detection of nucleic acid by coupling an autonomous cascade target replication and enzyme/gold nanoparticle-based post amplification. AB - Owing to the intrinsic importance of nucleic acid as bio-targets, the development of isothermal and ultrasensitive electrochemical DNA biosensor is very essential for biological studies and medical diagnostics. Herein, the autonomous cascade DNA replication strategy was effectively married with the enzyme/gold nanoparticle-based post-amplification strategy to promote the detection performance toward target DNA. A hairpin DNA probe (HP) is designed that consists of an overhang at 3'-end as the recognition unit for target DNA, a recognition site for nicking endonuclease, and an alkane spacer to terminate polymerization reaction. The autonomous DNA replication-scission-displacement reaction operated by the nicking endonuclease/KF polymerase induced the autocatalytic opening of HP, which was then specifically bound by the enzyme/gold nanoparticles for further dual-signal amplification toward target-related sensing events. A low detection limit of 0.065 fM with an excellent selectivity toward target DNA could be achieved. The proposed biosensor could be also easily regenerated for target detection. The developed biosensor creates an opportunity for the effective coupling of the target replication with post-amplification strategies and thus opens a promising avenue for the detection of nucleic acid with low abundance in bioanalysis and clinical biomedicine. PMID- 26849347 TI - Out of sight, out of mind? Does terminating the physical presence of a geriatric consultant in the community clinic reduce the implementation rate for geriatric recommendations. AB - AIM: To assess the effect of moving the geriatric consultation from the primary care clinic to another setting, on the rate of implementation of geriatric recommendations by family physicians. METHODS: A retrospective review of the computerized medical records of elderly patients in four primary care clinics. The rate of implementation of geriatric recommendations was compared between clinics in which a geriatric consultant was physically present (control clinics) and a clinic where the consultation took place elsewhere (study clinic). In addition, the results of the present study were compared to a previous study in which the geriatric consultation was carried out in the study clinic and the family doctor was an active participant. RESULTS: 127 computerized files were reviewed in the study clinic and 133 in the control clinics. The mean age of the patients was 81.1+/-6.3 years and 63.1% were women. The overall implementation of geriatric recommendations by family doctors in the study clinic was 55.9%, a statistically significant decrease compared to the previous study where the rate was 73.9% (p<0.0001). In contrast, there was no change in the implementation rate in the control clinics at 65.0% in the present study and 59.9% in the previous one (p=0.205). CONCLUSIONS: Direct, person-to-person contact between the geriatric consultant and the family doctor has a beneficial effect on the implementation of geriatric recommendations. This should be considered by healthcare policy makers when planning geriatric services in the community. PMID- 26849350 TI - Pyrolytic Temperature Dependent and Ash Catalyzed Formation of Sludge Char with Ultra-High Adsorption to 1-Naphthol. AB - Massively produced sewage sludge brings a serious problem to environment. Pyrolysis is a promising and bifunctional technology to dispose the sewage sludge and recover energy, in which a large amount of pyrolytic sludge char is also produced. In this study, we proposed a value-added utilization of sludge char. We prepared an adsorbent with ultrahigh capacity for hydrophobic organic pollutant (1-naphthol) by pyrolysis of sludge and removal of the ash moiety from the sludge char. The adsorptive behavior of the adsorbent is strongly dependent on the pyrolytic temperature of sludge, and the maximum adsorption capacity of 666 mg g( 1) was achieved at 800 degrees C, which is comparable to deliberately modified graphene. Further exploration indicated that the robust adsorption to 1-naphthol is attributed to the catalytic effect of ash in sludge which facilitated the formation of more orderly graphitic structures and aromaticity at high pyrolytic temperatures. PMID- 26849349 TI - Role of Vibrio cholerae exochitinase ChiA2 in horizontal gene transfer. AB - Vibrio cholerae exochitinase ChiA2 plays a key role in acquisition of nutrients by chitin hydrolysis in the natural environment as well as in pathogenesis in the intestinal milieu. In this study we demonstrate the importance of ChiA2 in horizontal gene transfer in the natural environment. We found that the expression of ChiA2 and TfoX, the central regulator of V. cholerae horizontal gene transfer, varied with changes in environmental conditions. The activity of ChiA2 was also dependent on these conditions. In 3 different environmental conditions tested here, we observed that the supporting environmental condition for maximum expression and activity of ChiA2 was 20 degrees C, pH 5.5, and 100 mmol/L salinity in the presence of chitin. The same condition also induced TfoX expression and was favorable for horizontal gene transfer in V. cholerae. High performance liquid chromatography analysis showed that ChiA2 released a significant amount of (GlcNAc)2 from chitin hydrolysis under the favorable condition. We hypothesized that under the favorable environmental condition, ChiA2 was upregulated and maximally active to produce a significant amount of (GlcNAc)2 from chitin. The same environmental condition also induced tfoX expression, followed by its translational activation by the (GlcNAc)2 produced, leading to efficient horizontal gene transfer. PMID- 26849351 TI - Successful detection of a minute tonsillar cancer lesion on transoral examination with narrow band imaging: A report of 2 cases. AB - BACKGROUND: The improvement of optical enhancement devices, such as narrow band imaging (NBI), has enabled us to visualize lesions that cannot be seen upon macroscopic examination. NBI is useful for detecting subtle lesions, including the primary sites of occult primary cancer. METHODS AND RESULTS: We describe 2 cases of tiny tonsillar cancer with positive p16 staining. Case 1 was as an occult primary cancer, and case 2 had a foreign body sensation of the pharynx. With transoral examination using a flexible video-laryngoscope with NBI, we successfully detected tonsillar cancer. These patients were treated with surgery, and the patients are currently alive with no evidence of disease more than 1 year posttreatment. CONCLUSION: We detected a small primary lesion in the palatine tonsil through transoral examination with NBI, which is a simple and noninvasive method. This approach may be useful to detect subtle lesions, especially in patients with human papillomavirus (HPV)-related tonsillar cancer. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2421-E2424, 2016. PMID- 26849352 TI - Advances in understanding gender difference in cardiometabolic disease risk. AB - Gender differences exist in cardiovascular or metabolic disease risk, beyond the protective effect of estrogens, mostly burdening the postmenopausal female. We aimed to review herein sex differences in pro-inflammatory states, the independence of inflammation from insulin resistance, differences in high-density lipoprotein dysfunction, in gene-environment interactions, and in the influence of current and former smoking on cardiometabolic risk. Sex differences in absorption of long-chain fatty acids are highlighted. Differences exist in the first manifestation of cardiovascular disease, men being more likely to develop coronary heart disease as a first event, compared to women who have cerebrovascular disease or heart failure as a first event. Autoimmune activation resulting from pro-inflammatory states, a fundamental mechanism for numerous chronic diseases in people prone to metabolic syndrome, is much more common in women, and these constitute major determinants. Therapeutic approaches to aspects related to sex difference are briefly reviewed. PMID- 26849353 TI - Interleukin-6 Levels in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis. AB - BACKGROUND: The change of serum interleukin-6(IL-6) levels in women with polycystic ovary syndrome (PCOS), as well as the relations between IL-6 levels and body mass index (BMI), insulin resistance(IR) and androgen status of PCOS patients, are not fully understood. METHODS: A literature search was performed in October 2015 using PubMed, Embase and the Cochrane Library databases to identify studies. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). RESULTS: Twenty articles with 25 case-control studies included 1618 women (922 PCOS patients and 696 controls) were included in this study. IL-6 levels in controls were significantly lower than that of PCOS patients (SMD = 0.78, 95%CI = 0.41-1.16, P<0.001), with significant heterogeneity across studies (I2 = 91% and P<0.001). Meta-regression analysis model indicated IR status was the main source of heterogeneity (P = 0.005). Results from group analysis suggested that high IL-6 levels in PCOS were significantly associated with Homeostasis Model Assessment of Insulin Resistance (HOMA2-IR) ratio and total testosterone ratio (T ratio), and was found in both lean and obese women with PCOS. Cumulative meta-analysis results indicated the total effect size (SMD) had tend to be stable since 2012(0.79 to 0.92). CONCLUSIONS: A high IL-6 level is not an intrinsic characteristic of PCOS, but may be a useful monitoring biomarker for the treatment of PCOS. PMID- 26849354 TI - Enantioselective Decarboxylative Arylation of alpha-Amino Acids via the Merger of Photoredox and Nickel Catalysis. AB - An asymmetric decarboxylative Csp(3)-Csp(2) cross-coupling has been achieved via the synergistic merger of photoredox and nickel catalysis. This mild, operationally simple protocol transforms a wide variety of naturally abundant alpha-amino acids and readily available aryl halides into valuable chiral benzylic amines in high enantiomeric excess, thereby producing motifs found in pharmacologically active agents. PMID- 26849355 TI - Network Analysis of a Comprehensive Knowledge Repository Reveals a Dual Role for Ceramide in Alzheimer's Disease. AB - Alzheimer's disease (AD) is the most common cause of senile dementia. Many inflammatory factors such as amyloid-beta and pro-inflammatory cytokines are known to contribute to the inflammatory response in the AD brain. Sphingolipids are widely known to have roles in the pathogenesis of inflammatory diseases, where the precise roles for sphingolipids in inflammation-associated pathogenesis of AD are not well understood. Here we performed a network analysis to clarify the importance of sphingolipids and to model relationships among inflammatory factors and sphingolipids in AD. In this study, we have updated sphingolipid signaling and metabolic cascades in a map of AD signaling networks that we named "AlzPathway," a comprehensive knowledge repository of signaling pathways in AD. Our network analysis of the updated AlzPathway indicates that the pathways related to ceramide are one of the primary pathways and that ceramide is one of the important players in the pathogenesis of AD. The results of our analysis suggest the following two prospects about inflammation in AD: (1) ceramide could play important roles in both inflammatory and anti-inflammatory pathways of AD, and (2) several factors such as Sphingomyelinase and Siglec-11 may be associated with ceramide related inflammation and anti-inflammation pathways in AD. In this study, network analysis of comprehensive knowledge repository reveals a dual role for ceramide in AD. This result provides a clue to clarify sphingolipids related inflammatory and anti-inflammatory pathways in AD. PMID- 26849356 TI - Influence of Snowmelt Timing on the Diet Quality of Pyrenean Rock Ptarmigan (Lagopus muta pyrenaica): Implications for Reproductive Success. AB - The Pyrenean rock ptarmigan (Lagopus muta pyrenaica) is the southernmost subspecies of the species in Europe and is considered threatened as a consequence of changes in landscape, human pressure, climate change, and low genetic diversity. Previous studies have shown a relationship between the date of snowmelt and reproductive success in the Pyrenean ptarmigan. It is well established that birds laying early in the breeding season have higher reproductive success, but the specific mechanism for this relationship is debated. We present an explicative model of the relationship between snowmelt date and breeding success mediated by food quality for grouse in alpine environments. From microhistological analyses of 121 faecal samples collected during three years in the Canigou Massif (Eastern Pyrenees), and the assessment of the chemical composition of the main dietary components, we estimated the potential quality of individual diets. Potential dietary quality was correlated with free-urate faecal N, a proxy of the digestible protein content ingested by ptarmigan, and both were correlated with phenological stage of consumed plants, which in turn depends on snowmelt date. Our findings suggest that the average snowmelt date is subject to a strong interannual variability influencing laying date. In years of early snowmelt, hens benefit from a longer period of high quality food resources potentially leading to a higher breeding success. On the contrary, in years of late snowmelt, hens begin their breeding period in poorer nutrient condition because the peaks of protein content of their main food items are delayed with respect to laying date, hence reducing breeding performance. We discuss the possible mismatch between breeding and snowmelt timing. PMID- 26849357 TI - Prevalence of Comorbidities, Overweight and Obesity in an International Sample of People with Multiple Sclerosis and Associations with Modifiable Lifestyle Factors. AB - Multiple sclerosis (MS) is a chronic neurological disorder, often affecting young people. Comorbid disorders such as depression, anxiety and hypertension are common and can affect disease course, treatment, and quality of life (QOL) of people with MS (PwMS). The associations between comorbidities, body mass index (BMI) and health outcomes are not well studied in MS, although research shows most PwMS are overweight. Most data on the prevalence of comorbidities and obesity in PwMS comes from North American populations. This study describes the prevalence of comorbidities, overweight and obesity and associations with modifiable factors in an international sample of PwMS recruited online through social media, MS societies and websites. The online survey consisted of validated and researcher-devised instruments to assess self-reported health outcomes and lifestyle behaviors. Of the 2399 respondents, 22.5% were overweight, 19.4% were obese and 67.2% reported at least one comorbidity, with back pain (36.2%), depression (31.7%), anxiety (29.1%) and arthritis (13.7%) most prevalent and most limiting in daily activities. Obesity and most comorbid disorders were significantly more prevalent in North America. Obese participants were more likely to have comorbidities, especially diabetes (OR 4.8) and high blood pressure (OR 4.5) but also depression (OR 2.2). Being overweight, obese, or a former, or current smoker was associated with an increase in the number of comorbidities; while healthy diet, physical activity (borderline significant) and moderate alcohol consumption were associated with decreased number of comorbidities. Increasing number of comorbidities was related to worse QOL, increased odds of disability and prior relapse. Obese PwMS had higher odds of disability and lower QOL. The associations between BMI, comorbidities and health outcomes are likely to be bi-directional and associated with lifestyle behaviors. Preventing and treating comorbid disorders and obesity in PwMS is warranted, and advice regarding healthy and risky lifestyle may assist in improving health outcomes. PMID- 26849358 TI - Rabies in the Baltic States: Decoding a Process of Control and Elimination. AB - Rabies is a fatal zoonosis that still causes nearly 70, 000 human deaths every year. In Europe, the oral rabies vaccination (ORV) of red foxes (Vulpes vulpes) was developed in the late 1970s and has demonstrated its effectiveness in the eradication of the disease in Western and some Central European countries. Following the accession of the three Baltic countries--Estonia, Latvia and Lithuania--to the European Union in 2004, subsequent financial support has allowed the implementation of regular ORV campaigns since 2005-2006. This paper reviews ten years of surveillance efforts and ORV campaigns in these countries resulting in the near eradication of the disease. The various factors that may have influenced the results of vaccination monitoring were assessed using generalized linear models (GLMs) on bait uptake and on herd immunity. As shown in previous studies, juveniles had lower bait uptake level than adults. For the first time, raccoon dogs (Nyctereutes procyonoides) were shown to have significantly lower bait uptake proportion compared with red foxes. This result suggests potentially altered ORV effectiveness in this invasive species compared to the red foxes. An extensive phylogenetic analysis demonstrated that the North East European (NEE) rabies phylogroup is endemic in all three Baltic countries. Although successive oral vaccination campaigns have substantially reduced the number of detected rabies cases, sporadic detection of the C lineage (European part of Russian phylogroup) underlines the risk of reintroduction via westward spread from bordering countries. Vaccine induced cases were also reported for the first time in non-target species (Martes martes and Meles meles). PMID- 26849360 TI - Phosphate removal and recovery from water using nanocomposite of immobilized magnetite nanoparticles on cationic polymer. AB - A novel nanocomposite (NC) based on magnetite nanoparticles (Fe3O4-NPs) immobilized on the surface of a cationic exchange polymer, C100, using a modification of the co-precipitation method was developed to obtain magnetic NCs for phosphate removal and recovery from water. High-resolution transmission electron microscopy-energy-dispersive spectroscopy, scanning electron microscopy , X-ray diffraction, and inductively coupled plasma optical emission spectrometry were used to characterize the NCs. Continuous adsorption process by the so-called breakthrough curves was used to determine the adsorption capacity of the Fe3O4 based NC. The adsorption capacity conditions were studied under different conditions (pH, phosphate concentration, and concentration of nanoparticles). The optimum concentration of iron in the NC for phosphate removal was 23.59 mgFe/gNC. The sorption isotherms of this material were performed at pH 5 and 7. Taking into account the real application of this novel material in real water, the experiments were performed at pH 7, achieving an adsorption capacity higher than 4.9 mgPO4-P/gNC. Moreover, Freundlich, Langmuir, and a combination of them fit the experimental data and were used for interpreting the influence of pH on the sorption and the adsorption mechanism for this novel material. Furthermore, regeneration and reusability of the NC were tested, obtaining 97.5% recovery of phosphate for the first cycle, and at least seven cycles of adsorption-desorption were carried out with more than 40% of recovery. Thus, this work described a novel magnetic nanoadsorbent with properties for phosphate recovery in wastewater. PMID- 26849359 TI - Risk Factors for Long-Term Mortality after Hospitalization for Community-Acquired Pneumonia: A 5-Year Prospective Follow-Up Study. AB - BACKGROUND: Contributors to long-term mortality in patients with community acquired pneumonia (CAP) remain unclear, with little attention paid to pneumonia etiology. We examined long-term survival, causes of death, and risk factors for long-term mortality in adult patients who had been hospitalized for CAP, with emphasis on demographic, clinical, laboratory, and microbiological characteristics. METHODS: Two hundred and sixty-seven consecutive patients admitted in 2008-2011 to a general hospital with CAP were prospectively recruited and followed up. Patients who died during hospital stay were excluded. Demographic, clinical, and laboratory data were collected within 48 hours of admission. Extensive microbiological work-up was performed to establish the etiology of CAP in 63% of patients. Mortality data were obtained from the Norwegian Cause of Death Registry. Cox regression models were used to identify independent risk factors for all-cause mortality. RESULTS: Of 259 hospital survivors of CAP (median age 66 years), 79 (30.5%) died over a median of 1,804 days (range 1-2,520 days). Cumulative 5-year survival rate was 72.9% (95% CI 67.4 78.4%). Standardized mortality ratio was 2.90 for men and 2.05 for women. The main causes of death were chronic obstructive pulmonary disease (COPD), vascular diseases, and malignancy. Independent risk factors for death were the following (hazard ratio, 95% CI): age (1.83 per decade, 1.47-2.28), cardiovascular disease (2.63, 1.61-4.32), COPD (2.09, 1.27-3.45), immunocompromization (1.98, 1.17 3.37), and low serum albumin level at admission (0.75 per 5 g/L higher, 0.58 0.96), whereas active smoking was protective (0.32, 0.14-0.74); active smokers were younger than non-smokers (P < 0.001). Microbial etiology did not predict mortality. CONCLUSIONS: Results largely confirm substantial comorbidity-related 5 year mortality after hospitalization for CAP and the impact of several well-known risk factors for death, and extend previous findings on the prognostic value of serum albumin level at hospital admission. Pneumonia etiology had no prognostic value, but this remains to be substantiated by further studies using extensive diagnostic microbiological methods in the identification of causative agents of CAP. PMID- 26849361 TI - The Affective Slider: A Digital Self-Assessment Scale for the Measurement of Human Emotions. AB - Self-assessment methods are broadly employed in emotion research for the collection of subjective affective ratings. The Self-Assessment Manikin (SAM), a pictorial scale developed in the eighties for the measurement of pleasure, arousal, and dominance, is still among the most popular self-reporting tools, despite having been conceived upon design principles which are today obsolete. By leveraging on state-of-the-art user interfaces and metacommunicative pictorial representations, we developed the Affective Slider (AS), a digital self-reporting tool composed of two slider controls for the quick assessment of pleasure and arousal. To empirically validate the AS, we conducted a systematic comparison between AS and SAM in a task involving the emotional assessment of a series of images taken from the International Affective Picture System (IAPS), a database composed of pictures representing a wide range of semantic categories often used as a benchmark in psychological studies. Our results show that the AS is equivalent to SAM in the self-assessment of pleasure and arousal, with two added advantages: the AS does not require written instructions and it can be easily reproduced in latest-generation digital devices, including smartphones and tablets. Moreover, we compared new and normative IAPS ratings and found a general drop in reported arousal of pictorial stimuli. Not only do our results demonstrate that legacy scales for the self-report of affect can be replaced with new measurement tools developed in accordance to modern design principles, but also that standardized sets of stimuli which are widely adopted in research on human emotion are not as effective as they were in the past due to a general desensitization towards highly arousing content. PMID- 26849362 TI - Correction: An Analysis of the Binding Characteristics of a Panel of Recently Selected ICAM-1 Binding Plasmodium falciparum Patient Isolates. PMID- 26849363 TI - Exome-Wide Association Analysis of Coronary Artery Disease in the Kingdom of Saudi Arabia Population. AB - Coronary Artery Disease (CAD) remains the leading cause of mortality worldwide. Mortality rates associated with CAD have shown an exceptional increase particularly in fast developing economies like the Kingdom of Saudi Arabia (KSA). Over the past twenty years, CAD has become the leading cause of death in KSA and has reached epidemic proportions. This rise is undoubtedly caused by fast urbanization that is associated with a life-style that promotes CAD. However, the question remains whether genetics play a significant role and whether genetic susceptibility is increased in KSA compared to the well-studied Western European populations. Therefore, we performed an Exome-wide association study (EWAS) in 832 patients and 1,076 controls of Saudi Arabian origin to test whether population specific, strong genetic risk factors for CAD exist, or whether the polygenic risk score for known genetic risk factors for CAD, lipids, and Type 2 Diabetes show evidence for an enriched genetic burden. Our results do not show significant associations for a single genetic locus. However, the heritability estimate for CAD for this population was high (h(2) = 0.53, S.E. = 0.1, p = 4e( 12)) and we observed a significant association of the polygenic risk score for CAD that demonstrates that the population of KSA, at least in part, shares the genetic risk associated to CAD in Western populations. PMID- 26849364 TI - Genome Wide Association Study of Seedling and Adult Plant Leaf Rust Resistance in Elite Spring Wheat Breeding Lines. AB - Leaf rust is an important disease, threatening wheat production annually. Identification of resistance genes or QTLs for effective field resistance could greatly enhance our ability to breed durably resistant varieties. We applied a genome wide association study (GWAS) approach to identify resistance genes or QTLs in 338 spring wheat breeding lines from public and private sectors that were predominately developed in the Americas. A total of 46 QTLs were identified for field and seedling traits and approximately 20-30 confer field resistance in varying degrees. The 10 QTLs accounting for the most variation in field resistance explained 26-30% of the total variation (depending on traits: percent severity, coefficient of infection or response type). Similarly, the 10 QTLs accounting for most of the variation in seedling resistance to different races explained 24-34% of the variation, after correcting for population structure. Two potentially novel QTLs (QLr.umn-1AL, QLr.umn-4AS) were identified. Identification of novel genes or QTLs and validation of previously identified genes or QTLs for seedling and especially adult plant resistance will enhance understanding of leaf rust resistance and assist breeding for resistant wheat varieties. We also developed computer programs to automate field and seedling rust phenotype data conversions. This is the first GWAS study of leaf rust resistance in elite wheat breeding lines genotyped with high density 90K SNP arrays. PMID- 26849366 TI - Fall prevention in the young old using an exoskeleton human body posturizer: a randomized controlled trial. AB - BACKGROUND: Fall risk in elderly has been related with physical decline, low quality of life and reduced survival. AIM: To evaluate the impact of exoskeleton human body posturizer (HBP) on the fall risk in the elderly. METHODS: 150 subjects (mean age 64.85; 79 M/71 F) with mild fall risk were randomized into two groups: 75 for group treated with human body posturizer (HBP group) and 75 for physical training without HBP group (exercise group). The effects of interventions were assessed by differences in tests related to balance and falls. Medically eligible patients were screened with Tinetti balance and Gait evaluation scale, short physical performance battery and numeric pain rating scale to determine fall risk in elderly people. RESULTS: In the HBP group there was a significant improvement in short physical performance battery, Tinetti scale and Pain Numeric rating scale with a significant reduction in fall risk (p < 0.05). In the exercise group we observed only minimal variations in the test scores. DISCUSSION: The results at the sixth and twelfth months show a twofold positive effect in the HBP group reducing fall risk and improving quality of life by reducing pain. CONCLUSION: The use of exoskeleton human body posturizer seems to be a new significant device for prevention of fall in elderly patients. Further research should be carried out to obtain more evidence on effects of robotic technology for fall prevention in the elderly. PMID- 26849365 TI - Biomarkers of Exposure to Polycyclic Aromatic Hydrocarbons and Cognitive Function among Elderly in the United States (National Health and Nutrition Examination Survey: 2001-2002). AB - Recent studies report a link between common environmental exposures, such as particulate matter air pollution and tobacco smoke, and decline in cognitive function. The purpose of this study was to assess the association between exposure to polycyclic aromatic hydrocarbons (PAHs), a selected group of chemicals present in particulate matter and tobacco smoke, and measures of cognitive performance among elderly in the general population. This cross sectional analysis involved data from 454 individuals aged 60 years and older from the 2001-2002 National Health and Nutrition Examination Survey. The association between PAH exposures (as measured by urinary biomarkers) and cognitive function (digit symbol substitution test (DSST)) was assessed using multiple linear regression analyses. After adjusting for age, socio-economic status and diabetes we observed a negative association between urinary 1 hydroxypyrene, the gold standard of PAH exposure biomarkers, and DSST score. A one percent increase in urinary 1-hydroxypyrene resulted in approximately a 1.8 percent poorer performance on the digit symbol substitution test. Our findings are consistent with previous publications and further suggest that PAHs, at least in part may be responsible for the adverse cognitive effects linked to tobacco smoke and particulate matter air pollution. PMID- 26849367 TI - Neural Androgen Receptor Deletion Impairs the Temporal Processing of Objects and Hippocampal CA1-Dependent Mechanisms. AB - We studied the role of testosterone, mediated by the androgen receptor (AR), in modulating temporal order memory for visual objects. For this purpose, we used male mice lacking AR specifically in the nervous system. Control and mutant males were gonadectomized at adulthood and supplemented with equivalent amounts of testosterone in order to normalize their hormonal levels. We found that neural AR deletion selectively impaired the processing of temporal information for visual objects, without affecting classical object recognition or anxiety-like behavior and circulating corticosterone levels, which remained similar to those in control males. Thus, mutant males were unable to discriminate between the most recently seen object and previously seen objects, whereas their control littermates showed more interest in exploring previously seen objects. Because the hippocampal CA1 area has been associated with temporal memory for visual objects, we investigated whether neural AR deletion altered the functionality of this region. Electrophysiological analysis showed that neural AR deletion affected basal glutamate synaptic transmission and decreased the magnitude of N-methyl-D aspartate receptor (NMDAR) activation and high-frequency stimulation-induced long term potentiation. The impairment of NMDAR function was not due to changes in protein levels of receptor. These results provide the first evidence for the modulation of temporal processing of information for visual objects by androgens, via AR activation, possibly through regulation of NMDAR signaling in the CA1 area in male mice. PMID- 26849368 TI - Changes in Soluble CD18 in Murine Autoimmune Arthritis and Rheumatoid Arthritis Reflect Disease Establishment and Treatment Response. AB - INTRODUCTION: In rheumatoid arthritis (RA) immune activation and presence of autoantibodies may precede clinical onset of disease, and joint destruction can progress despite remission. However, the underlying temporal changes of such immune system abnormalities in the inflammatory response during treat-to-target strategies remain poorly understood. We have previously reported low levels of the soluble form of CD18 (sCD18) in plasma from patients with chronic RA and spondyloarthritis. Here, we study the changes of sCD18 before and during treatment of early RA and following arthritis induction in murine models of rheumatoid arthritis. METHODS: The level of sCD18 was analyzed with a time resolved immunoflourometric assay in 1) plasma from early treatment naive RA patients during a treat-to-target strategy (the OPERA cohort), 2) plasma from chronic RA patients, 3) serum from SKG and CIA mice following arthritis induction, and 4) supernatants from synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from 6 RA patients cultured with TNFalpha or adalimumab. RESULTS: Plasma levels of sCD18 were decreased in chronic RA patients compared with early RA patients and in early RA patients compared with healthy controls. After 12 months of treatment the levels in early RA patients were similar to healthy controls. This normalization of plasma sCD18 levels was more pronounced in patients with very early disease who achieved an early ACR response. Plasma sCD18 levels were associated with radiographic progression. Correspondingly, the serum level of sCD18 was decreased in SKG mice 6 weeks after arthritis induction compared with healthy littermates. The sCD18 levels in both SKG and CIA mice exhibited a biphasic course after arthritis induction with an initial increase above baseline followed by a decline. Shedding of CD18 from RA SFMC and RA PBMC cultures was increased by TNFalpha and decreased by adalimumab. CONCLUSIONS: The plasma sCD18 levels were altered in patients with RA, in mice with autoimmune arthritis and in cell cultures treated with TNFalpha and adalimumab. Decreased levels of plasma sCD18 could reflect autoimmunity in transition from early to chronic disease and normalization in response to treatment could reflect autoimmunity in remission. PMID- 26849370 TI - Correction: Behavior of Tilted Angle Shear Connectors. PMID- 26849369 TI - A Vector with a Single Promoter for In Vitro Transcription and Mammalian Cell Expression of CRISPR gRNAs. AB - The genomes of more than 50 organisms have now been manipulated due to rapid advancement of gene editing technology. One way to perform gene editing in the mouse using the CRISPR/CAS system, guide RNA (gRNA) and CAS9 mRNA transcribed in vitro are microinjected into fertilized eggs that are then allowed to develop to term. As a rule, gRNAs are tested first in tissue culture cells and the one with the highest locus-specific cleavage activity is chosen for microinjection. For cell transfections, gRNAs are typically expressed using the human U6 promoter (hU6). However, gRNAs for microinjection into zygotes are obtained by in vitro transcription from a T7 bacteriophage promoter in a separate plasmid vector. Here, we describe the design and construction of a combined U6T7 hybrid promoter from which the same gRNA sequence can be expressed. An expression vector containing such a hybrid promoter can now be used to generate gRNA for testing in mammalian cells as well as for microinjection purposes. The gRNAs expressed and transcribed from this vector are found to be functional in cells as well as in mice. PMID- 26849371 TI - Blockage of the Ryanodine Receptor via Azumolene Does Not Prevent Mechanical Ventilation-Induced Diaphragm Atrophy. AB - Mechanical ventilation (MV) is a life-saving intervention for patients in respiratory failure. However, prolonged MV causes the rapid development of diaphragm muscle atrophy, and diaphragmatic weakness may contribute to difficult weaning from MV. Therefore, developing a therapeutic countermeasure to protect against MV-induced diaphragmatic atrophy is important. MV-induced diaphragm atrophy is due, at least in part, to increased production of reactive oxygen species (ROS) from diaphragm mitochondria and the activation of key muscle proteases (i.e., calpain and caspase-3). In this regard, leakage of calcium through the ryanodine receptor (RyR1) in diaphragm muscle fibers during MV could result in increased mitochondrial ROS emission, protease activation, and diaphragm atrophy. Therefore, these experiments tested the hypothesis that a pharmacological blockade of the RyR1 in diaphragm fibers with azumolene (AZ) would prevent MV-induced increases in mitochondrial ROS production, protease activation, and diaphragmatic atrophy. Adult female Sprague-Dawley rats underwent 12 hours of full-support MV while receiving either AZ or vehicle. At the end of the experiment, mitochondrial ROS emission, protease activation, and fiber cross sectional area were determined in diaphragm muscle fibers. Decreases in muscle force production following MV indicate that the diaphragm took up a sufficient quantity of AZ to block calcium release through the RyR1. However, our findings reveal that AZ treatment did not prevent the MV-induced increase in mitochondrial ROS emission or protease activation in the diaphragm. Importantly, AZ treatment did not prevent MV-induced diaphragm fiber atrophy. Thus, pharmacological inhibition of the RyR1 in diaphragm muscle fibers is not sufficient to prevent MV induced diaphragm atrophy. PMID- 26849372 TI - Flexibility of Physiological Traits Underlying Inter-Individual Growth Differences in Intertidal and Subtidal Mussels Mytilusgalloprovincialis. AB - Mussel seed (Mytilusgalloprovincialis) gathered from the intertidal and subtidal environments of a Galician embayment (NW, Spain) were maintained in the laboratory during five months to select fast (F) and slow (S) growing mussels. The physiological basis underlying inter-individual growth variations were compared for F and S mussels from both origins. Fast growing seemed to be a consequence of greater energy intake (20% higher clearance and ingestion rate) and higher food absorption rate coupled with low metabolic costs. The enhanced energy absorption (around 65% higher) resulted in 3 times higher Scope for Growth in F mussels (20.5+/-4.9 J h(-1)) than S individuals (7.3+/-1.1 J h(-1)). The higher clearance rate of F mussels appears to be linked with larger gill filtration surface compared to S mussels. Intertidal mussels showed higher food acquisition and absorption per mg of organic weight (i.e. mass-specific standardization) than subtidal mussels under the optimal feeding conditions of the laboratory. However, the enhanced feeding and digestive rates were not enough to compensate for the initial differences in tissue weight between mussels of similar shell length collected from the intertidal and subtidal environments. At the end of the experiment, subtidal individuals had higher gill efficiency, which probably lead to higher total feeding and absorption rates relative to intertidal individuals. PMID- 26849373 TI - Calcification on CT is a simple and valuable preoperative indicator of 1p/19q loss of heterozygosity in supratentorial brain tumors that are suspected grade II and III gliomas. AB - Gliomas with 1p/19q loss of heterozygosity (LOH) are known to be associated with longer patient survival and higher sensitivity to treatment than tumors without 1p/19q LOH. This study was designed to clarify whether the preoperative finding of calcification on CT was correlated with 1p/19q LOH in patients with suspected WHO grade II and III gliomas. This study included 250 adult patients who underwent resection for primary supratentorial tumors at Tokyo Women's Medical University Hospital. The tumors were suspected, based on MRI findings, to be WHO grade II or III gliomas. The presence of calcification on the patients' CT images was qualitatively evaluated before treatment. After surgery, the resected tumors were examined to determine their 1p/19q status and mutations of IDH1 and p53. The presence of calcification was significantly correlated with 1p/19q LOH (P < 0.0001), with a positive predictive value of 91 %. The tumors of all the 78 patients with calcification were diagnosed as oligodendroglial tumors. Seventy of these patients showed classic oligodendroglial features, while 8 patients showed non-classic features. Calcification on CT is a simple and valuable preoperative indicator of 1p/19q LOH in supratentorial brain tumors that are suspected to be WHO grade II and III gliomas. PMID- 26849375 TI - Men and women should be separately investigated in studies of orthostatic challenge due to different gender-related dynamics of autonomic response. AB - In studies of autonomic regulation during orthostatic challenges only a few nonlinear methods have been considered without investigating the effect of gender in young controls. Especially, the temporal development of the autonomic regulation has not yet been explicitly analyzed using short-term segments in supine position, transition and orthostatic phase (OP). In this study, nonlinear analysis of cardiovascular and respiratory time series was performed to investigate how nonlinear indices are dynamically changing with respect to gender during orthostatic challenges. The analysis was carried out using shifted short term segments throughout a head-up tilt test in 24 healthy subjects, 12 men (26 +/- 4 years) and 12 age-matched women (26 +/- 5 years), at supine position and during OP at 70 degrees . The nonlinear methods demonstrated statistical differences in the autonomic regulation between males and females. Orthostatic stress caused significantly decreased heart rate variability due to increased sympathetic activity mainly in men, already at the beginning and during the complete OP, revealed by (a) increased occurrence of specific word types with constant fluctuations as pW111 from symbolic dynamics, (b) augmented fractal correlation properties by the short-term index alpha1 from detrended fluctuation analysis, (c) increased slope indices (21ati and 31ati) from auto transinformation and (d) augmented time irreversibility indices demonstrating more temporal asymmetries and nonlinear dynamics in men than in women. After tilt up, both men and women increased their sympathetic activity but in a different way. Time-dependent gender differences during orthostatic challenge were shown directly between men and women or indirectly comparing baseline and different temporal stages of OP. The proposed dynamical study of autonomic regulation has the advantage of screening the fluctuations of the sympathetic and vagal activities that can be quantified by the temporal behavior of nonlinear indices. The findings in this paper strongly suggest the need for gender separation in studies of the dynamics of autonomic regulation during orthostatic challenge. PMID- 26849374 TI - Frequency specific brain networks in Parkinson's disease and comorbid depression. AB - The topological organization underlying the human brain was extensively investigated using resting-state functional magnetic resonance imaging, focusing on a low frequency of signal oscillation from 0.01 to 0.1 Hz. However, the frequency specificities with regard to the topological properties of the brain networks have not been fully revealed. In this study, a novel complementary ensemble empirical mode decomposition (CEEMD) method was used to separate the fMRI time series into five characteristic oscillations with distinct frequencies. Then, the small world properties of brain networks were analyzed for each of these five oscillations in patients (n = 67) with depressed Parkinson's disease (DPD, n = 20) , non-depressed Parkinson's disease (NDPD, n = 47) and healthy controls (HC, n = 46). Compared with HC, the results showed decreased network efficiency in characteristic oscillations from 0.05 to 0.12 Hz and from 0.02 to 0.05 Hz for the DPD and NDPD patients, respectively. Furthermore, compared with HC, the most significant inter-group difference across five brain oscillations was found in the basal ganglia (0.01 to 0.05 Hz) and paralimbic-limbic network (0.02 to 0.22 Hz) for the DPD patients, and in the visual cortex (0.02 to 0.05 Hz) for the NDPD patients. Compared with NDPD, the DPD patients showed reduced efficiency of nodes in the basal ganglia network (0.01 to 0.05 Hz). Our results demonstrated that DPD is characterized by a disrupted topological organization in large-scale brain functional networks. Moreover, the CEEMD analysis suggested a prominent dissociation in the topological organization of brain networks between DPD and NDPD in both space and frequency domains. Our findings indicated that these characteristic oscillatory activities in different functional circuits may contribute to distinct motor and non-motor components of clinical impairments in Parkinson's disease. PMID- 26849376 TI - Expression of 58-kD Microspherule Protein (MSP58) is Highly Correlated with PET Imaging of Tumor Malignancy and Cell Proliferation in Glioma Patients. AB - BACKGROUND/AIMS: The nucleolar 58-kDa microspherule protein (MSP58) has important transcriptional regulation functions and plays a crucial role in the tumorigenesis and progression of cancers. 3'-deoxy-3'-[18F]fluorothymidine (FLT) has emerged as a promising positron emission tomography (PET) tracer for evaluating tumor malignancy and cell proliferation. METHODS: In the present study, the expression of MSP58 was evaluated by immunohistochemistry and the corresponding PET image was examined using FLT-PET in 55 patients with various grades of gliomas. RESULTS: The immunoreactivity score (IRS) of MSP58 increased with tumor grade with grade IV gliomas exhibiting the highest expression and showed a highly significant positive correlation with the Ki-67 index (r = 0.65, P < 0.001). The IRS of MSP58 in the tumor showed a highly significant positive correlation with corresponding FLT uptake value (r = 0.61, P < 0.001). The correlation between MSP58 expression and glioma malignancy was also confirmed by immunofluorescence, RT-PCR and western blot analysis. FLT uptake value also exhibited a highly significant positive correlation with the Ki-67 index (r = 0.59, P < 0.001). Kaplan-Meier analysis revealed that MSP58 expression has a significant prognostic ability for the overall survival time similar to that found in the uptake value of FLT-PET. CONCLUSION: These results indicate that MSP58 plays an important role in cell proliferation and will be one of the potential candidates of molecular therapy targeting proliferation. FLT-PET might be used as an early measure of treatment response in the proliferation-targeted therapy. PMID- 26849377 TI - Prevalence of Multiple Sclerosis in the Republic of Moldova. AB - BACKGROUND: The occurrence of multiple sclerosis (MS) increases in populations featuring both high and low disease burden, and variations across regions at the same latitude are reported. MS epidemiological data in Eastern Europe are scarce and out of date. We report on sex- and age-specific prevalence of MS in the Republic of Moldova. METHODS: Benefitting from a nationwide survey aimed to quantify the MS burden in Moldovans (3,559,541 population in 2012), multiple epidemiological sources were scrutinized. RESULTS: On prevalence day, December 31, 2012, 747 MS patients (McDonald criteria) resided in the study area, yielding a crude prevalence of 20.9 per 100,000 (95% CI 14.7-27.1), 25.7 (95% CI 20.5 30.5) in women and 15.8 (95% CI 12.2-19.3) in men (F:M ratio of 1.63), and standardized estimates of 20.2, 24.3 and 15.5 per 100,000, respectively. Prevalence was highest in the age group 40-49 years (43.9 per 100,000) and higher in rural (72.6%) than in urban (27.4%) areas. CONCLUSIONS: This is the first report on sex- and age-specific prevalence of MS in the Republic of Moldova, which was lower than in Europe on average, but consistent with that of neighboring countries, Romania and Ukraine. Moldovans represent a population wherein MS natural history is not yet influenced by use of disease-modifying drugs. PMID- 26849378 TI - [Winged scapula in lyme borreliosis]. AB - Here we present the case of a young patient with one-sided winged scapula and lyme borreliosis. This disease can be very delimitating in daily life. If non operative treatment fails, dynamic or static stabilization of the scapula can be a therapeutic option. PMID- 26849380 TI - Aryl Nitriles from Alkynes Using tert-Butyl Nitrite: Metal-Free Approach to C=C Bond Cleavage. AB - Alkyne C=C bond breaking, outside of alkyne metathesis, remains an underdeveloped area in reaction discovery. Recently, nitrogenation has been reported to allow nitrile formation from alkynes. A new protocol for the metal-free C=C bond cleavage of terminal alkynes to produce nitriles is reported. This method provides an opportunity to synthesize a vast range of nitriles containing aryl, heteroaryl, and natural product derivatives (38 examples). In addition, the potential of (t)BuONO to act as a powerful nitrogenating agent for terminal aryl alkynes is demonstrated. PMID- 26849379 TI - The inheritance of corneal endothelial cell density. AB - BACKGROUND: Although it is known that some corneal diseases and degenerations have a significant heritable background, heritability on corneal endothelial cell density (ECD) has never been clearly determined. Our aim was to determine the heritability of corneal ECD. MATERIAL AND METHODS: Corneal ECD of 114 eyes (66 eyes of 33 monozygotic and 48 eyes of 24 dizygotic pairs; mean age 49.0 +/- 15.5 years) was investigated by Konan Noncon Robo NSP-9900 specular microscopy. Structural equation modeling (ACE model) was applied. RESULTS: Endothelial corneal cell density was highly heritable (82.0%, 95%CI, 70.0-92.0%), whereas the unique environmental contribution was 18.0% (95%CI, 8.0-29.0%). Shared environmental factors had no influence on the endothelial corneal cell density. DISCUSSION: In this twin study, we established first that the density of the corneal endothelial cells is strongly heritable, which should stimulate future genetic studies to identify genes and pathways that are involved in determining ECD which might in turn lead to future treatments to prevent EC loss. PMID- 26849381 TI - Cost of skeletal complications from bone metastases in six European countries. AB - Objective Patients with bone metastases or lesions secondary to solid tumors or multiple myeloma often experience bone complications (skeletal-related events [SREs]-radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression); however, recent data that can be used to assess the value of treatments to prevent SREs across European countries are limited. This study aimed to provide estimates of health resource utilization (HRU) and cost associated with all SRE types in Europe. HRU data were reported previously; cost data are reported herein. Methods Eligible patients from 49 centers across Austria (n = 57), the Czech Republic (n = 59), Finland (n = 60), Greece (n = 59), Portugal (n = 59), and Sweden (n = 62) had bone metastases or lesions secondary to breast, lung, or prostate cancer, or multiple myeloma, and >=1 index SRE (a SRE preceded by a SRE-free period of >= 6.5 months). SRE-related costs were estimated from a payer perspective using health resource utilization data from patient charts (before and after the index SRE diagnosis). Country-specific unit costs were from 2010 and local currencies were converted to 2010 euros. Results The mean costs across countries were ?7043, ?5242, ?11,101, and ?11,509 per radiation to bone, pathologic fracture, surgery to bone, and spinal cord compression event, respectively. Purchasing power parity (PPP)-adjusted mean cost ratios were similar in most countries, with the exception of radiation to bone. Limitations The overall burden of SREs may have been under-estimated owing to home visits and evaluations outside the hospital setting not being reported here. Conclusions All SREs were associated with substantial costs. Variation in SRE associated costs between countries was most likely driven by differences in treatment practices and unit costs. PMID- 26849382 TI - LONG-TERM OUTCOMES IN PATIENTS WITH VITREOMACULAR TRACTION TREATED WITH A SINGLE INTRAVITREAL INJECTION OF OCRIPLASMIN. AB - PURPOSE: To report long-term outcomes in patients with vitreomacular traction injected with intravitreal ocriplasmin. METHODS: Interventional case series. PATIENTS: A 64-year-old woman and a 46-year-old woman. RESULTS: In Case 1, a 64 year-old woman with focal vitreomacular traction with impending macular hole presented with a visual acuity of 20/80 +1 and was injected with ocriplasmin 11 days later. Visual acuity continued to improve and stabilized through 60 weeks of follow-up with a final visual acuity of 20/50. Vitreomacular traction release was confirmed by optical coherence tomography 6 weeks after injection.In Case 2, a 46 year-old woman with focal vitreomacular traction presented with a visual acuity of 20/60 and received ocriplasmin treatment the same day. Vitreomacular traction release was confirmed by optical coherence tomography 2 days later. After subsequent worsening of visual acuity, pneumatic retinopexy and pars plana vitrectomy were performed. Visual acuity continued to improve and stabilize throughout the 52-week follow-up with a final visual acuity of 20/25. CONCLUSION: We present here two patients with focal vitreomacular traction treated with ocriplasmin and followed up long-term for up to one year. In both cases, visual acuity improved compared with baseline and stabilized after ocriplasmin treatment. These cases add to the growing literature demonstrating resolution of symptoms after ocriplasmin treatment over longer follow-up periods. PMID- 26849383 TI - Management of Candida biofilms: state of knowledge and new options for prevention and eradication. AB - Biofilms formed by Candida species (spp.) on medical devices represent a potential health risk. The focus of current research is searching for new options for the treatment and prevention of biofilm-associated infections using different approaches including modern nanotechnology. This review summarizes current information concerning the most relevant resistance/tolerance mechanisms to conventional drugs and a role of additional factors contributing to these phenomena in Candida spp. (mostly Candida albicans). Additionally, it provides an information update in prevention and eradication of a Candida biofilm including experiences with 'lock' therapy, potential utilization of small molecules in biomedical applications, and perspectives of using photodynamic inactivation in the control of a Candida biofilm. PMID- 26849384 TI - Dynamics of Spatially Confined Bisphenol A Trimers in a Unimolecular Network on Ag(111). AB - Bisphenol A (BPA) aggregates on Ag(111) shows a polymorphism between two supramolecular motifs leading to formation of distinct networks depending on thermal energy. With rising temperature a dimeric pairing scheme reversibly converts into a trimeric motif, which forms a hexagonal superstructure with complex dynamic characteristics. The trimeric arrangements notably organize spontaneously into a self-assembled one-component array with supramolecular BPA rotors embedded in a two-dimensional stator sublattice. By varying the temperature, the speed of the rotors can be controlled as monitored by direct visualization. A combination of scanning tunneling microscopy and dispersion corrected density-functional tight-binding (DFTB-vdW(surf)) based molecular modeling reveals the exact atomistic position of each molecule within the assembly as well as the driving force for the formation of the supramolecular rotors. PMID- 26849385 TI - Lewis Acid Catalyzed Synthesis of Cyanidophosphates. AB - Salts containing new cyanido(fluorido)phosphate anions of the general formula [PF6-n(CN)n](-) (n=1-4) were synthesized by a very mild Lewis-acid-catalyzed synthetic protocol and fully characterized. All [PF6-n(CN)n](-) (n=1-4) salts could be isolated on a preparative scale. It was also possible to detect the [PF(CN)5](-) but not the [P(CN)6](-) anion. The best results with respect to purity, yield, and low cost were obtained when the F(-)/CN(-) substitution reactions were carried out in ionic liquids. PMID- 26849386 TI - Systematic Review and Meta-Analysis of Avascular Necrosis and Posttraumatic Arthritis After Traumatic Hip Dislocation. AB - OBJECTIVES: To determine the incidence rate and associative factors for the development of avascular necrosis (AVN) and posttraumatic arthritis (PTA) after traumatic hip dislocation and time to reduction. DATA SOURCES: A comprehensive search of databases including PubMed, Cochrane Database, and Embase through April 2014 for English articles reporting complications of AVN and PTA after hip dislocation was performed. STUDY SELECTION: Inclusion criteria were English-only studies, a patient population of adults, study outcomes of AVN and/or PTA reported, and articles reported at least type I dislocations. DATA EXTRACTION: Two authors independently extracted data from the selected studies and the data collected were compared to verify agreement. DATA SYNTHESIS: Random-effects models were used for meta-analysis. The overall event rate of AVN and PTA was calculated and stratified based on Thompson-Epstein of the hip dislocation. Odds ratios were calculated for those articles that reported rates of AVN based on time to reduction. CONCLUSIONS: For anterior dislocations, the event rate for AVN ranged from 0.087 to 0.333, whereas the event rate for PTA ranged from 0.125 to 0.700. Analysis of posterior dislocations revealed that the event rate for AVN ranged from 0.106 to 0.430; additionally, the event rate for PTA ranged from 0.194 to 0.586. For posterior hip dislocations and type I and II anterior dislocations, the severity of the injury correlates with an increase in the development of AVN and PTA. The odds ratio of AVN for those hip dislocations reduced after 12 hours versus those reduced before 12 hours was 5.627. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 26849387 TI - Knee Injury Associated With Acetabular Fractures: A Multicenter Study of 1273 Patients. AB - OBJECTIVES: The purpose of this study was to determine the incidence and pattern of the knee injury associated with acetabular fractures. DESIGN: Retrospective cohort study. SETTING: Three level I and one level II trauma centers. PATIENTS: A total of 1273 skeletally mature patients treated at 4 trauma centers between November 2004 and December 2013 for acetabular fractures were retrospectively identified from orthopaedic trauma databases. INTERVENTION: Analysis of all acetabular fractures with knee injury regarding type of acetabular fracture, mechanism of injury, energy of injury, pattern of the knee injury, knee examination findings at initial presentation, intraoperative and on follow-up, requirement for surgery/conservative management, and the associated injuries. The clinical data entered during inpatient stay and office visits were analyzed. MAIN OUTCOME MEASURES: Incidence and pattern of the knee injury. RESULTS: One hundred ninety-three of 1273 patients (15%) were found to have ipsilateral knee symptoms within a period of 1 year from the date of injury. The patterns of knee injury included 56 fractures (29%), 49 ligamentous lesions (25%), and 88 miscellaneous (46%) causes including bone bruises, wounds, and swelling. Associated injuries included 85 patients with ipsilateral hip dislocation (45%), 59 pelvic injuries (31%), 61 extremity injuries (32%), 38 head injuries (20%), 37 chest injuries (20%), 23 abdominal and genitourinary injuries (12%), and 7 injuries of the spine (4%). CONCLUSION: Based on this study, we conclude that knee injuries associated with high-energy acetabular fractures constitute a significant portion of the patient population. Ligament injuries are frequently overlooked and thorough clinical evaluation and utilization of magnetic resonance imaging in selected cases will help in early detection and prevention of long-term complications. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. PMID- 26849388 TI - Rotationally Stable Screw-Anchor With Locked Trochanteric Stabilizing Plate Versus Proximal Femoral Nail Antirotation in the Treatment of AO/OTA 31A2.2 Fracture: A Biomechanical Evaluation. AB - OBJECTIVES: Third-generation cephalomedullary nails currently represent the gold standard in the treatment of unstable trochanteric femur fractures. Recently, an extramedullary rotationally stable screw-anchor system (RoSA) has been developed. It was designed to combine the benefits of screw and blade and to improve stability using a locked trochanteric stabilizing plate (TSP). The purpose of this study was to compare the biomechanical behavior of RoSA/TSP and the proximal femoral nail antirotation (PFNA). METHODS: Standardized AO/OTA 31A2.2 fractures were induced by an oscillating saw in 10 paired human specimens (n = 20; mean age = 85 years; range: 71-96 years). The fractures were stabilized by either the RoSA/TSP (Koenigsee Implants, Allendorf, Germany) or the PFNA (DePuy Synthes, Zuchwil, Switzerland). Femurs were positioned in 25 degrees of adduction and 10 degrees of posterior flexion and were cyclically loaded with axial sinusoidal pattern at 0.5 Hz, starting at 300 N, with stepwise increase by 300 N every 500 cycles until bone-implant failure occurred. After every load step, the samples were measured visually and radiographically. Femoral head migration was assessed. RESULTS: The stiffness at the load up to the clinically relevant load step of 1800 N (639 +/- 378 N/mm (RoSA/TSP) vs. 673 +/- 227 N/mm (PFNA); P = 0.542) was comparable, as was the failure load (3000 +/- 787 N vs. 3780 +/- 874 N; P = 0.059). Up to 1800 N, no femoral head rotation, head migration, or femoral neck shortening were observed either for RoSA/TSP or PFNA. Whereas failure of the PFNA subsumed fractures of the greater trochanter and the lateral wall, a posterior femoral neck fracture with a significantly increased femoral neck shortening (1.7 mm vs. 0 mm; P = 0.012) was the cause of failure with RoSA/TSP. This specific kind of failure was induced by a femoral neck weakening caused by the posterior TSP stabilizing screw. CONCLUSIONS: There was no significant difference in biomechanical properties between the RoSA/TSP and the PFNA for the fracture pattern tested. However, failure modes differed between the 2 implants with greater femoral neck shortening observed in the RoSA/TSP group. PMID- 26849389 TI - Errata. PMID- 26849390 TI - Early Mechanical Failures of the Synthes Variable Angle Locking Distal Femur Plate. AB - OBJECTIVES: To document the high failure rate of a specific implant: the Synthes Variable Angle (VA) Locking Distal Femur Plate. DESIGN: Retrospective. SETTING: Urban University Level I Trauma Center. PATIENT/PARTICIPANTS: All distal femur fractures (OTA/AO 33-A, B, C) treated from March 2011 through August 2013 were reviewed from our institutional orthopaedic trauma registry. Inclusion criteria were fractures treated with a precontoured distal femoral locking plate and age between 18 and 84. Exclusion criteria were fractures treated with intramedullary nails, arthroplasty, non-precontoured plates, dual plating, or screw fixation alone. The population was divided into 3 groups: less invasive stabilization system (LISS) group (n = 21), treated with LISS plates (Synthes, Paoli, PA); locking condylar plates (LCPs) group (n = 10), treated with LCPs (Synthes, Paoli, PA); and VA group (n = 36), treated with VA distal femoral LCPs (Synthes, Paoli, PA). Average age was 54.6 +/- 17.5 years. INTERVENTION: Open reduction internal fixation with one of the above implants was performed. MAIN OUTCOME MEASURES: The patients were followed radiographically for early mechanical implant failure defined as loosening of locking screws, loss of fixation, plate bending, or implant failure. RESULTS: There were no statistically significant differences between groups for age, gender, open fracture, mechanism of injury, or medial comminution. There were 3 failures (14.3%) in group LISS, no failures (0%) in group LCP, and 8 failures (22.2%) in group VA. All 3 failures in group LISS were in A-type fractures (2 periprosthetic) and all failures in group VA were in C type fractures. When all fractures for all 3 groups were compared for failure rate, there was no statistically significant difference (P = 0.23). However, when only 33-C fractures were compared, there was significantly greater failure rate in the VA group (P = 0.03). The mean time to failure in group VA was 147 days (range 24-401 days) and was significantly earlier (P = 0.034) when compared with group LISS (mean 356 days; range 251-433 days). CONCLUSIONS: Early mechanical failure with the VA distal femoral locking plate is higher than traditional locking plates (LCP and LISS) for OTA/AO 33-C fractures. We caution practicing surgeons against the use of this plate for metaphyseal fragmented distal femur fractures. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. PMID- 26849392 TI - Highly Sensitive and Selective Surface-Enhanced Raman Spectroscopy Label-free Detection of 3,3',4,4'-Tetrachlorobiphenyl Using DNA Aptamer-Modified Ag-Nanorod Arrays. AB - An improved label-free approach for highly sensitive and selective detection of 3,3',4,4'-tetrachlorobiphenyl (PCB-77), a type of polychlorinated biphenyl, via surface-enhanced Raman spectroscopy (SERS) using DNA aptamer-modified Ag-nanorod arrays as the effective substrate is reported. The devised system consists of Ag nanorod (Ag-NR) arrays with the PCB-77 binding aptamers anchored covalently to the Ag surfaces through a thiol linker. The aptamers are made of single-stranded DNA (ssDNA) oligomers, with one end standing on the Ag surface, and upon conjugation with PCB-77, the ssDNA molecules can change their conformation to hairpin loops, so that the Raman intensity of guanines at the other end of the DNA strand increases accordingly. As such, the intensity ratio I(656 cm( 1))/I(733 cm(-1)) increases concomitantly with the increase of the concentration of PCB-77, making the quantitative evaluation of trace amounts of PCB-77 attainable. Moreover, it is found that the DNA aptamer-based Ag-NR arrays can be more responsive with a lower and optimal density of the DNA molecules modified on the substrate surface, and the best sensitivity for detection of PCB-77 can be achieved with the lower detection limit approaching 3.3 * 10(-8) M. This work therefore demonstrates that the design of aptamer-modified Ag-NRs can be used as a practically promising SERS substrate for label-free trace detection of persistent organic pollutants (POPs) in the environment. PMID- 26849393 TI - Breastfeeding: a reproductive factor able to reduce the risk of luminal B breast cancer in premenopausal White women. AB - In the medical literature, the role of breastfeeding and reproductive factors in the risk of breast carcinoma is still an open debate in premenopausal women. We highlight the role of breastfeeding and reproductive factors in luminal A and luminal B, the most frequent breast cancers. This case-control study analyzes a White premenopausal population of 286 breast cancer patients, divided into molecular subtypes, and 578 controls matched by age. Multivariate logistic regression models were used to assess the relationships of breastfeeding and other reproductive factors (age at menarche, parity, age at first pregnancy, number of children) with the risk of breast cancers. Among the variables examined, reproductive factors did not alter the risk of cancer, whereas breastfeeding up to 12 months was a significant protective factor against luminal B breast cancer (multivariate odds ratio: 0.22, 95% confidence interval: 0.09 0.59, P=0.002). In contrast, luminal A cases did not significantly correlate with breastfeeding or other reproductive factors. Breastfeeding up to 12 months is strongly protective against the more aggressive luminal B, but not against the less aggressive luminal A breast cancer in premenopausal White women. PMID- 26849395 TI - Laparoscopic Appendectomy for Chronic Right Iliac Fossa Pain: Correlating Histology with Outcome. AB - BACKGROUND: Chronic right iliac fossa (CRIF) pain in children is associated with repeated hospital attendance, inconclusive investigations, and missed school days. There is increasing evidence for the role of laparoscopic appendectomy for the management of CRIF pain. However, currently there is no substantial evidence to correlate histological changes identified in the appendixes removed with resolution of pain. METHOD: This study collected prospective data for a single surgeon's series of laparoscopic appendectomy performed for CRIF pain between 2003 and 2014. RESULTS: Forty patients with a median age of 13 years (range 5-19 years) underwent laparoscopic appendectomy for CRIF pain. Twenty-nine patients (73%) had macroscopically normal appendixes, but histological changes were identified in 28 patients (70%). Other findings at laparoscopy included gynecological pathology (ovarian/para-ovarian cysts), unfixed mobile caecum, and a well-defined peritoneal band extending from the caecum to the anterolateral abdominal wall (caeco-peritoneal band). Patients were followed up for a median of 2 months (range 1-15 months). All patients reported resolution of CRIF pain. DISCUSSION: Laparoscopic appendectomy appears to be an effective treatment for CRIF pain, while also providing the opportunity to diagnose and treat potential sources of CRIF pain other than the appendix. Consistent with the literature, a small number of patients appear to have resolution of pain, despite no histological change being identified in the appendix removed and no other pathology having been identified. The same histological changes commonly seen have also been demonstrated in appendixes removed incidentally. Caution therefore should be applied when interpreting the significance of histological changes seen. PMID- 26849394 TI - Community-acquired pneumonia in primary care: clinical assessment and the usability of chest radiography. AB - OBJECTIVES: To investigate the diagnostic value of different clinical and laboratory findings in pneumonia and to explore the association between the doctor's degree of suspicion and chest X-ray (CXR) result and to evaluate whether or not CXR should be used routinely in primary care, when available. DESIGN: A three-year prospective study was conducted between September 2011 and December 2014. SETTING: Two primary care settings in Linkoping, Sweden. SUBJECTS: A total of 103 adult patients with suspected pneumonia in primary care. MAIN OUTCOME MEASURES: The physicians recorded results of a standardized medical physical examination, including laboratory results, and rated their suspicion into three degrees. The outcome of the diagnostic variables and the degree of suspicion was compared with the result of CXR. RESULTS: Radiographic pneumonia was reported in 45% of patients. When the physicians were sure of the diagnosis radiographic pneumonia was found in 88% of cases (p < 0.001), when quite sure the frequency of positive CXR was 45%, and when not sure 28%. Elevated levels of C-reactive protein (CRP) >= 50mg/L were associated with the presence of radiographic pneumonia when the diagnosis was suspected (p < 0.001). CONCLUSION: This study indicates that CXR can be useful if the physician is not sure of the diagnosis, but when sure one can rely on one's judgement without ordering CXR. KEY POINTS: There are different guidelines but no consensus on how to manage community acquired pneumonia in primary care. When the physician is sure of the diagnosis the judgement is reliable without chest X-ray and antibiotics can be safely prescribed. Chest X-ray can be useful in the assessment of pneumonia in primary care, when the physician is not sure of the diagnosis. PMID- 26849397 TI - Competency Evaluations in the Next Accreditation System: Contributing to Guidelines and Implications. AB - CONSTRUCT: This study examines validity evidence of end-of-rotation evaluation scores used to measure competencies and milestones as part of the Next Accreditation System (NAS) of the Accreditation Council for Graduate Medical Education (ACGME). BACKGROUND: Since the implementation of the milestones, end-of rotation evaluations have surfaced as a potentially useful assessment method. However, validity evidence on the use of rotation evaluation scores as part of the NAS has not been studied. This article examines validity evidence for end-of rotation evaluations that can contribute to developing guidelines that support the NAS. APPROACH: Data from 2,701 end-of-rotation evaluations measuring 21 out of 22 Internal Medicine milestones for 142 residents were analyzed (July 2013 June 2014). Descriptive statistics were used to measure the distribution of ratings by evaluators (faculty, n = 116; fellows, n = 59; peer-residents, n = 131), by postgraduate years. Generalizability analysis and higher order confirmatory factor analysis were used to examine the internal structure of ratings. Psychometric implications for combining evaluation scores using composite score reliability were examined. RESULTS: Milestone ratings were significantly higher for each subsequent year of training (15/21 milestones). Faculty evaluators had greater variability in ratings across milestones, compared to fellows and residents; faculty ratings were generally correlated with milestone ratings from fellows (r = .45) and residents (r = .25), but lower correlations were found for Professionalism and Interpersonal and Communication Skills. The Phi-coefficient was .71, indicating good reliability. Internal structure supported a 6-factor solution, corresponding to the hierarchical relationship between the milestones and the 6 core competencies. Evaluation scores corresponding to Patient Care, Medical Knowledge, and Practice-Based Learning and Improvement had higher correlations to milestones reported to the ACGME. Mean evaluation ratings predicted problem residents (odds ratio = 5.82, p < .001). CONCLUSIONS: Guidelines for rotation evaluations proposed in this study provide useful solutions that can help program directors make decisions on resident progress and contribute to assessment systems in graduate medical education. PMID- 26849396 TI - Overexpression of WDR79 in non-small cell lung cancer is linked to tumour progression. AB - WD-repeat protein 79 (WDR79), a member of the WD-repeat protein family, acts as a scaffold protein, participating in telomerase assembly, Cajal body formation and DNA double-strand break repair. Here, we first report that WDR79 is frequently overexpressed in cell lines and tissues derived from non-small cell lung cancer (NSCLC). Knockdown of WDR79 significantly inhibited the proliferation of NSCLC cells in vitro and in vivo by inducing cell cycle arrest and apoptosis. WD-repeat protein 79 -induced cell cycle arrest at the G0/G1 phase was associated with the expression of G0/G1-related cyclins and cyclin-dependent kinase complexes. We also provide evidence that WDR79 knockdown induces apoptosis via a mitochondrial pathway. Collectively, these results suggest that WDR79 is involved in the tumorigenesis of NSCLC and is a potential novel diagnostic marker and therapeutic target for NSCLC. PMID- 26849398 TI - Heart attacks prevent chocolate. Or, the differences between correlation and causation. PMID- 26849399 TI - Acupuncture-Induced Analgesia: The Role of Microglial Inhibition. AB - The last three decades have documented preclinical and clinical data supporting the use of acupuncture in relieving symptoms of many diseases, including allergies, infections, and neurological disorders. The advent of electroacupuncture has not only modernized the practice of acupuncture, but also has improved its efficacy, especially for producing analgesic-like effects. Although the mechanism of action of acupuncture-induced analgesia remains largely unknown, several lines of investigation have implicated modulation of pain processes via brain opioid signaling and neuroimmunoregulatory pathways. Here, we review key findings demonstrating the efficacy and underlying mechanisms of acupuncture-induced analgesia. In particular, we discuss potent analgesic effects of acupuncture via neural pain processes through inhibition of microglial activation. The safe and effective use of acupuncture stands as a nonpharmacological alternative for induction of analgesia, which has direct clinical applications, especially for pain-related diseases. PMID- 26849400 TI - Energy utilization, nitrogen balance and microbial protein supply in cattle fed Pennisetum purpureum and condensed tannins. AB - The aim of the experiment was to assess the effect of condensed tannins (CT) on feed intake, dry matter digestibility, nitrogen balance, supply of microbial protein to the small intestine and energy utilization in cattle fed a basal ration of Pennisetum purpureum grass. Five heifers (Bos taurus * Bos indicus) with an average live weight of 295 +/- 19 kg were allotted to five treatments consisting of increasing levels of CT (0, 1, 2, 3 and 4% CT/kg DM) in a 5 * 5 Latin square design. Dry matter intake (DMI) was similar (p > 0.05) between treatments containing 0, 1, 2 and 3% of CT/kg DM and it was reduced (p < 0.05) to 4% CT (5.71 kg DM/day) with respect to that observed with 0% CT (6.65 kg DM/day). Nitrogen balance, purine derivatives excretion in urine, microbial protein synthesis and efficiency of synthesis of microbial nitrogen in the rumen were not affected (p >= 0.05) by the increase in the levels of condensed tannins in the ration. Energy loss as CH4 was on average 2.7% of the gross energy consumed daily. Metabolizable energy intake was 49.06 MJ/day in cattle fed low-quality tropical grass with a DMI of 6.27 kg/day. It is concluded that concentrations of CT between 2 and 3% of DM of ration reduced energy loss as CH4 by 31.3% and 47.6%, respectively, without affecting intakes of dry and organic matter; however, digestibilities of dry and organic matter are negatively affected. PMID- 26849402 TI - Task Analysis as a Resource for Strengthening Health Systems. AB - Task analysis is a descriptive study methodology that has wide application in the health professions. Task analysis is particularly useful in assessment and definition of the knowledge, skills, and behaviors that define the scope of practice of a health profession or occupation. Jhpiego, a US-based nongovernmental organization, has adapted traditional task analysis methods in several countries in assessment of workforce education and practice issues. Four case studies are presented to describe the utility and adaptability of the task analysis approach. Traditional task analysis field survey methods were used in assessment of the general and maternal-child health nursing workforce in Mozambique that led to curriculum redesign, reducing the number of education pathways from 4 to 2. The process of health system strengthening in Liberia, following a long history of civil war conflict, included a traditional task analysis study conducted among 119 registered nurses and 46 certified midwives who had graduated in the last 6 months to 2 years to determine gaps in education and preparation. An innovative approach for data collection that involves "playing cards" to document participant opinions (Task Master, Mining for Data) was developed by Jhpiego for application in other countries. Results of a task analysis involving 54 nurses and 100 nurse-midwives conducted in Lesotho were used to verify the newly drafted scope and standards of practice for nurses and to inform planning for a competency-based preservice curriculum for nursing. The Nursing and Midwifery Council developed a 100-question licensing examination for new graduates following a task analysis in Botswana. The task analysis process in each country resulted in recommendations that were action oriented and were implemented by the country governments. For maximal utility and ongoing impact, a task analysis study should be repeated on a periodic basis and more frequently in countries undergoing rapid change in development of workforce policy. PMID- 26849403 TI - Specific gene patterns and molecular pathways related to human carcinogenesis in different populations among various geographic locations. PMID- 26849401 TI - Same sibling marrow following cord allogeneic transplantation as therapy for second relapse acute promyelocytic leukemia in a pediatric patient. AB - Optimal therapy for relapsed APL in pediatric patients is controversial. Allogeneic HSCT is an alternative, with event-free survival of 70-75%. We report a pediatric patient with APL who relapsed 28 months after CBT from her sibling and then was treated with BMT from the same donor. Bone marrow was selected for higher cell dose, donor availability, and partial donor chimerism. Persistent molecular remission was achieved, currently at 65 months after BMT. This case suggests the potential role of GVL activity in APL and illustrates the use of different cell sources from the same donor in allogeneic transplantation for pediatric patients. PMID- 26849404 TI - Enhancement of Peroxidase Release from Non-Malignant and Malignant Cells through Low-Dose Irradiation with Different Radiation Quality. AB - The release of peroxidase by nontransformed or transformed fibroblasts or epithelial cells (effector cells) triggers apoptosis induction selectively in transformed fibroblasts or transformed epithelial cells (target cells) through intercellular apoptosis-inducing signaling. The release of peroxidase can be induced either by treatment with transforming growth factor beta 1 or by low doses of alpha particles, gamma rays or ultrasoft X rays. In addiation, data indicates that radiation quality does not determine the overall efficiency of peroxidase release and the effects among a wide range of radiation doses are indistinguishable. These findings suggested that peroxidase release might be being triggered through intercellular bystander signaling. We show here that maximal peroxidase release does indeed occur after coculture of a small number of irradiated cells with an excess of unirradiated cells and demonstrate an enhanced effector function of nontransformed cells after the addition of a small number of irradiated cells. These data strongly indicate that peroxidase release is indeed triggered through bystander signaling mechanisms in mammalian cells. PMID- 26849405 TI - Inter-Relationship between Low-Dose Hyper-Radiosensitivity and Radiation-Induced Bystander Effects in the Human T98G Glioma and the Epithelial HaCaT Cell Line. AB - Over the past several years, investigations in both low-dose hyper radiosensitivity and increased radioresistance have been a focus of radiation oncology and biology research, since both conditions occur primarily in tumor cell lines. There has been significant progress in elucidating their signaling pathways, however uncertainties exist when they are studied together with radiation-induced bystander effects. Therefore, the aim of this work was to further investigate this relationship using the T98G glioma and HaCaT cell lines. T98G glioma cells have demonstrated a strong transition from hyper radiosensitivity to induced radioresistance, and HaCaT cells do not show low-dose hypersensitivity. Both cell lines were paired using a mix-and-match protocol, which involved growing nonirradiated cells in culture media from irradiated cells and covering all possible combinations between them. The end points analyzed were clonogenic cell survival and live calcium measurements through the cellular membrane. Our data demonstrated that T98G cells produced bystander signals that decreased the survival of both reporter T98G and HaCaT cells. The bystander effect occurred only when T98G cells were exposed to doses below 1 Gy, which was corroborated by the induction of calcium fluxes. However, when bystander signals originated from HaCaT cells, the survival fraction increased in reporter T98G cells while it decreased in HaCaT cells. Moreover, the corresponding calcium data showed no calcium fluxes in T98G cells, while HaCaT cells displayed a biphasic calcium profile. In conclusion, our findings indicate a possible link between low dose hyper-radiosensitivity and bystander effects. This relationship varies depending on which cell line functions as the source of bystander signals. This further suggests that the bystander mechanisms are more complex than previously expected and caution should be taken when extrapolating bystander results across all cell lines and all radiation doses. PMID- 26849406 TI - Cancer Stem cells and their cellular origins in primary liver and biliary tract cancers. AB - Liver and biliary tract cancers are highly aggressive, are heterogeneous in their phenotypic traits, and result in clinical outcomes that are difficult to manage. Cancers have subpopulations of cells termed "cancer stem cells" (CSCs) that share common intrinsic signaling pathways for self-renewal and differentiation with normal stem cells. These CSCs likely have the potential to evolve over time and to give rise to new genetically and functionally diverse subclones by accumulating genetic mutations. Extrinsic signaling from the tumor microenvironment, including the CSC niche, has been implicated in tumor initiation/progression and heterogeneity through dynamic crosstalk. CSCs have become recognized as pivotal sources of tumor initiation/progression, relapse/metastasis, and chemoresistance. CONCLUSION: The origins of CSCs are hypothesized to derive from the transformation of normal stem/progenitors and/or from the reprogramming of adult cells that converts them to stem/progenitor traits; however, the precise mechanisms have not yet been fully elucidated. (Hepatology 2016;64:645-651). PMID- 26849407 TI - The nucleus is a conserved mechanosensation and mechanoresponse organelle. AB - Cells in vivo exist in a dynamic environment where they experience variable mechanical influences. The precise mechanical environment influences cell-cell interactions, cell-extracellular matrix interactions, and in-turn, cell morphology and cell function. Therefore, the ability of each cell to constantly and rapidly alter their behavior in response to variations in their mechanical environment is essential for cell viability, development, and function. Mechanotransduction, the process by which mechanical force is translated into a biochemical signal to activate downstream cellular responses, is thus crucial to cell function during development and homeostasis. Although much research has focused on how protein complexes at the cell cortex respond to mechanical stress to initiate mechanotransduction, the nucleus has emerged as crucial to the ability of the cell to perceive and respond to changes in its mechanical environment. This additional method for mechanosensing allows for direct transmission of force through the cytoskeleton to the nucleus, which can increase the speed at which a cell changes its transcriptional profile. This review discusses recent work demonstrating the importance of the nucleus in mediating the cellular response to internal and external force, establishing the nucleus as an important mechanosensing organelle. PMID- 26849409 TI - Impact of an intervention for recently released homeless offenders on self reported re-arrest at 6 and 12 months. AB - A randomized controlled trial was conducted with 600 paroled men, homeless prior to incarceration, to assess varying levels of peer-coach and nurse-partnered interventions on re-arrest at 6 and 12 months. Findings revealed that positive predictors of re-arrest at 12 months included having received social support from drug users and non-drug users, as well as having used marijuana at least once a week prior to their most recent incarceration. In terms of protective factors, those who participated in a substance abuse program contract within a residential drug treatment program or spent 90 days or greater in a residential drug treatment program were less likely to have been re-arrested within 12 months. PMID- 26849410 TI - Pain self-management training increases self-efficacy, self-management behaviours and pain and depression outcomes. AB - BACKGROUND: Self-management practices among patients with medical and psychiatric comorbidity is not well understood. We assessed the effects of a combined pharmacological and behavioural intervention on self-efficacy to manage symptoms and self-management behaviours in patients with pain and comorbid depression. METHODS: Longitudinal analysis of self-management behaviours and their relationship with outcomes in a 12-month trial of 250 primary care patients with chronic musculoskeletal pain and comorbid depression. Participants were randomized to either usual care or an intervention that consisted of optimized antidepressant therapy followed by six sessions of a pain self-management (PSM) programme. RESULTS: Participants in the intervention group significantly increased the time spent performing self-management behaviours including strengthening and stretching exercises, progressive muscle relaxation and visualization at 12 months. Moreover, intervention participants reported greater self-efficacy to manage their pain and depression. The number of pain self management sessions received showed a dose-response relationship with improvement in both pain and depression severity. CONCLUSION: A combined intervention increased patient self-management behaviours and self-efficacy to manage symptoms among primary care patients with chronic musculoskeletal pain and depression. Receipt of the full dose of the entire PSM programme was related to improvements in pain interference and depression severity. WHAT DOES THIS STUDY ADD?: A nurse led six-session PSM programme increased self-efficacy as well as specific behaviours such as strengthening and stretching exercises, progressive muscle relaxation and visualization. There was a dose-response in that attending a greater proportion of the PSM sessions led to greater improvement in both pain and depression outcomes. PMID- 26849412 TI - Impact of the Nanoscale Gap Morphology on the Plasmon Coupling in Asymmetric Nanoparticle Dimer Antennas. AB - Coupling of plasmon resonances in metallic gap antennas is of interest for a wide range of applications due to the highly localized strong electric fields supported by these structures, and their high sensitivity to alterations of their structure, geometry, and environment. Morphological alterations of asymmetric nanoparticle dimer antennas with (sub)-nanometer size gaps are assigned to changes of their optical response in correlative dark-field spectroscopy and high resolution transmission electron microscopy (HR-TEM) investigations. This multimodal approach to investigate individual dimer structures clearly demonstrates that the coupling of the plasmon modes, in addition to well-known parameters such as the particle geometry and the gap size, is also affected by the relative alignment of both nanoparticles. The investigations corroborate that the alignment of the gap forming facets, and with that the gap area, is crucial for their scattering properties. The impact of a flat versus a rounded gap structure on the optical properties of equivalent dimers becomes stronger with decreasing gap size. These results hint at a higher confinement of the electric field in the gap and possibly a different onset of quantum transport effects for flat and rounded gap antennas in corresponding structures for very narrow gaps. PMID- 26849413 TI - Metformin-induced mitochondrial function and ABCD2 up-regulation in X-linked adrenoleukodystrophy involves AMP-activated protein kinase. AB - X-linked adrenoleukodystrophy (X-ALD) is a progressive neurometabolic disease caused by mutations/deletions in the Abcd1 gene. Similar mutations/deletions in the Abcd1 gene often result in diagonally opposing phenotypes of mild adrenomyeloneuropathy and severe neuroinflammatory cerebral adrenoleukodystrophy (ALD), which suggests involvement of downstream modifier genes. We recently documented the first evidence of loss of AMP-activated protein kinase alpha1 (AMPKalpha1) in ALD patient-derived cells. Here, we report the novel loss of AMPKalpha1 in postmortem brain white matter of patients with ALD phenotype. Pharmacological activation of AMPK can rescue the mitochondrial dysfunction and inhibit the pro-inflammatory response. The FDA approved anti-diabetic drug Metformin, a well-known AMPK activator, induces mitochondrial biogenesis and is documented for its anti-inflammatory role. We observed a dose-dependent activation of AMPKalpha1 in metformin-treated X-ALD patient-derived fibroblasts. Metformin also induced mitochondrial oxidative phosphorylation and ATP levels in X-ALD patient-derived fibroblasts. Metformin treatment decreased very long chain fatty acid levels and pro-inflammatory cytokine gene expressions in X-ALD patient derived cells. Abcd2 [adrenoleukodystrophy protein-related protein] levels were increased in metformin-treated X-ALD patient-derived fibroblasts and Abcd1-KO mice primary mixed glial cells. Abcd2 induction was AMPKalpha1-dependent since metformin failed to induce Abcd2 levels in AMPKalpha1-KO mice-derived primary mixed glial cells. In vivo metformin (100 mg/Kg) in drinking water for 60 days induced Abcd2 levels and mitochondrial oxidative phosphorylation protein levels in the brain and spinal cord of Abcd1-KO mice. Taken together, these results provide proof-of-principle for therapeutic potential of metformin as a useful strategy for correcting the metabolic and inflammatory derangements in X-ALD by targeting AMPK. There is no effective therapy for inherited peroxisomal disorder X-linked adrenoleukodystrophy (X-ALD). We document the therapeutic potential of FDA approved drug, Metformin, for X-ALD by targeting AMPK. Metformin induced peroxisomal Abcd2 levels in vitro and in vivo. Metformin lowered VLCFA levels, improved mitochondrial function and ameliorated inflammatory gene expression in X ALD patient-derived cells. Metformin-induced Abcd2 levels were dependent on AMPKalpha1, a metabolic and anti-inflammatory gene, recently documented by our laboratory to play a putative role in X-ALD pathology. Read the Editorial Highlight for this article on page 10. PMID- 26849408 TI - Atherogenesis: hyperhomocysteinemia interactions with LDL, macrophage function, paraoxonase 1, and exercise. AB - Despite great strides in understanding the atherogenesis process, the mechanisms are not entirely known. In addition to diet, cigarette smoking, genetic predisposition, and hypertension, hyperhomocysteinemia (HHcy), an accumulation of the noncoding sulfur-containing amino acid homocysteine (Hcy), is a significant contributor to atherogenesis. Although exercise decreases HHcy and increases longevity, the complete mechanism is unclear. In light of recent evidence, in this review, we focus on the effects of HHcy on macrophage function, differentiation, and polarization. Though there is need for further evidence, it is most likely that HHcy-mediated alterations in macrophage function are important contributors to atherogenesis, and HHcy-countering strategies, such as nutrition and exercise, should be included in the combinatorial regimens for effective prevention and regression of atherosclerotic plaques. Therefore, we also included a discussion on the effects of exercise on the HHcy-mediated atherogenic process. PMID- 26849414 TI - Optimization of AFLP for extremely large genomes over 70 Gb. AB - Here, we present an improved amplified fragment length polymorphism (AFLP) protocol using restriction enzymes (AscI and SbfI) that recognize 8-base pair sequences to provide alternative optimization suitable for species with a genome size over 70 Gb. This cost-effective optimization massively reduces the number of amplified fragments using only +3 selective bases per primer during selective amplification. We demonstrate the effects of the number of fragments and genome size on the appearance of nonidentical comigrating fragments (size homoplasy), which has a negative impact on the informative value of AFLP genotypes. We also present various reaction conditions and their effects on reproducibility and the band intensity of the extremely large genome of Viscum album. The reproducibility of this octo-cutter protocol was calculated using several species with genome sizes ranging from 1 Gb (Carex panicea) to 76 Gb (V. album). The improved protocol also succeeded in detecting high intraspecific variability in species with large genomes (V. album, Galanthus nivalis and Pinus pumila). PMID- 26849416 TI - Green tea catechins potentiate the effect of antibiotics and modulate adherence and gene expression in Porphyromonas gingivalis. AB - OBJECTIVES: A number of studies have brought evidence that green tea catechins may contribute to periodontal health. The objective of this study was to investigate the ability of a green tea extract and its principal constituent epigallocatechin-3-gallate (EGCG) to potentiate the antibacterial effects of antibiotics (metronidazole, tetracycline) against Porphyromonas gingivalis, and to modulate the adherence to oral epithelial cells and expression of genes coding for virulence factors and the high temperature requirement A (HtrA) stress protein in P. gingivalis. METHODS: A broth microdilution assay was used to determine the antibacterial activity of the green tea extract and EGCG. The synergistic effects of either compounds in association with metronidazole or tetracycline were evaluated using the checkerboard technique. A fluorescent assay was used to determine bacterial adherence to oral epithelial cells. The modulation of gene expression in P. gingivalis was evaluated by quantitative RT PCR. The Vibrio harveyi bioassay was used for monitoring quorum sensing inhibitory activity. RESULTS: The MIC values of the green tea extract on P. gingivalis ranged from 250 to 1000 MUg/ml, while those of EGCG ranged from 125 to 500 MUg/ml. A marked synergistic effect on P. gingivalis growth was observed for the green tea extract or EGCG in combination with metronidazole. Both the green tea extract and EGCG caused a dose-dependent inhibition of P. gingivalis adherence to oral epithelial cells. On the one hand, green tea extract and EGCG dose-dependently inhibited the expression of several P. gingivalis genes involved in host colonization (fimA, hagA, hagB), tissue destruction (rgpA, kgp), and heme acquisition (hem). On the other hand, both compounds increased the expression of the stress protein htrA gene. The ability of the green tea extract and EGCG to inhibit quorum sensing may contribute to the modulation of gene expression. CONCLUSIONS: This study explored the preventive and therapeutic potential of green tea catechins against periodontal disease. In addition to inhibit growth and adherence of P. gingivalis, a green tea extract and its main constituent EGCG was found to decrease the expression of genes coding for the major virulence factors. PMID- 26849418 TI - Anticlostridial agent 8-hydroxyquinoline improves the isolation of faecal bifidobacteria on modified Wilkins-Chalgren agar with mupirocin. AB - The need for suitable selective cultivation media for the isolation of Bifidobacterium spp. continues to be a real concern in the field of intestinal microbiology. Isolation of bifidobacteria from human and animal faecal samples using selective agar plating may be problematic especially in samples with increased clostridial counts than bifidobacterial counts. Due to the absence of anticlostridial agents in existing selective media, clostridia can displace bifidobacteria resulting in incorrect estimation of their counts. Therefore, we supplemented the existing selective medium 'modified Wilkins Chalgren agar with mupirocin' (MWM) with 90 mg l(-1) of 8-hydroxyquinoline (8HQ), which was recently proved to act selectively against clostridia. The newly composed 'modified Wilkins-Chalgren agar with 8HQ' (MWMQ) was tested on pure bifidobacterial and clostridial strains, their mixtures, and using faecal samples of mammalian origin; its selectivity was evaluated by genus-specific identification of isolates. The results demonstrated that the presence of 8HQ in this agar eliminated the growth of nonbifidobacterial strains on MWMQ compared to that on MWM, whereas the recovery of bifidobacterial counts was at satisfactory levels. In conclusion, MWMQ could be recommended for bifidobacterial isolation from human and animal faeces especially when bifidobacteria are not numerically dominant and there are chances of clostridial contamination. SIGNIFICANCE AND IMPACT OF THE STUDY: Routine isolation of bifidobacteria from mammalian faeces does not use a reliable selective agar with an anticlostridial agent. Overgrowth of clostridia may result in incorrect estimation of bifidobacterial counts. Thus, in order to improve the selectivity of existing media for bifidobacterial isolation, we chose the modified Wilkins-Chalgren agar with mupirocin and supplemented it with 8 hydroxyquinoline (8HQ), a molecule that shows anticlostridial activity without affecting the growth of bifidobacteria. This newly composed medium showed enhanced selectivity and specificity compared to the original medium and therefore, can be recommended for the isolation of bifidobacteria from mammal faeces. PMID- 26849419 TI - Cross-Interface Emulsification for Generating Size-Tunable Droplets. AB - We report cross-interface emulsification (XiE), a simple method for the generation of monodisperse droplets of controllable volumes from picoliter to nanoliter. A device is set up in which a fused-silica capillary is vibrating across the surface of the continuous phase (mineral oil) in a reservoir, and the flow of the dispersed phase (aqueous solution) in the capillary is segmented into monodisperse droplets at the air/oil interface. We find that the volume of droplets is mainly dominated by the flow rate and vibrating frequency and not significantly influenced by other factors, such as the viscosity of the continuous phase and dispersed phase, the inner diameter of the capillary (20-100 MUm), or the shape of the tip (tapered or flat). These features reflect high robustness, flexibility, and precision of XiE for on-demand volume control of droplets. The droplets automatically assemble into planar monolayer droplet arrays (PMDA) in flat-bottomed microwells of 96-well plates, offering excellent convenience for imaging of droplets. As a representative application, we carry out digital loop-mediated isothermal amplification using PMDAs with multivolume droplets for the absolute quantification of nucleic acids. Our results demonstrate that XiE is simple and controllable for the production of monodisperse size-tunable droplets, and it offers opportunities for common laboratories, even without microfabrication facilities, to perform digital quantification, single cell analysis, and other biochemical assays with high throughput. PMID- 26849417 TI - Gene Transfer of Brain-derived Neurotrophic Factor (BDNF) Prevents Neurodegeneration Triggered by FXN Deficiency. AB - Friedreich's ataxia is a predominantly neurodegenerative disease caused by recessive mutations that produce a deficiency of frataxin (FXN). Here, we have used a herpesviral amplicon vector carrying a gene encoding for brain-derived neurotrophic factor (BDNF) to drive its overexpression in neuronal cells and test for its effect on FXN-deficient neurons both in culture and in the mouse cerebellum in vivo. Gene transfer of BDNF to primary cultures of mouse neurons prevents the apoptosis which is triggered by the knockdown of FXN gene expression. This neuroprotective effect of BDNF is also observed in vivo in a viral vector-based knockdown mouse cerebellar model. The injection of a lentiviral vector carrying a minigene encoding for a FXN-specific short hairpin ribonucleic acid (shRNA) into the mouse cerebellar cortex triggers a FXN deficit which is accompanied by significant apoptosis of granule neurons as well as loss of calbindin in Purkinje cells. These pathological changes are accompanied by a loss of motor coordination of mice as assayed by the rota-rod test. Coinjection of a herpesviral vector encoding for BDNF efficiently prevents both the development of cerebellar neuropathology and the ataxic phenotype. These data demonstrate the potential therapeutic usefulness of neurotrophins like BDNF to protect FXN-deficient neurons from degeneration. PMID- 26849420 TI - Episodic feeling-of-knowing relies on noncriterial recollection and familiarity: Evidence using an online remember-know procedure. AB - We examined the hypothesis that feeling-of-knowing judgments rely on recollection as well as on familiarity prompted by the cue presentation. A remember-know-no memory procedure was combined with the episodic FOK procedure employing a cue target pair memory task. The magnitude of FOK judgments and FOK accuracy were examined as a function of recollection, familiarity, or the "no memory" option. Results showed that the proportion of R and K responses was similar. FOK accuracy and magnitude of FOK judgments were higher for R and K responses than for N responses. FOK accuracy related to R and K responses were above chance level, but FOK was not accurate in the "no memory" condition. Finally, both FOK magnitude and FOK accuracy were related more to recollection than to familiarity. These results support the hypothesis that both recollection and familiarity are determinants of the FOK process, although they suggest that recollection has a stronger influence. PMID- 26849422 TI - Computer assisted preoperative planning of bone fracture reduction: Simulation techniques and new trends. AB - The development of support systems for surgery significantly increases the likelihood of obtaining satisfactory results. In the case of fracture reduction interventions these systems enable surgery planning, training, monitoring and assessment. They allow improvement of fracture stabilization, a minimizing of health risks and a reduction of surgery time. Planning a bone fracture reduction by means of a computer assisted simulation involves several semiautomatic or automatic steps. The simulation deals with the correct position of osseous fragments and fixation devices for a fracture reduction. Currently, to the best of our knowledge there is no computer assisted methods to plan an entire fracture reduction process. This paper presents an overall scheme of the computer based process for planning a bone fracture reduction, as described above, and details its main steps, the most common proposed techniques and their main shortcomings. In addition, challenges and new trends of this research field are depicted and analyzed. PMID- 26849421 TI - Groupwise connectivity-based parcellation of the whole human cortical surface using watershed-driven dimension reduction. AB - Segregating the human cortex into distinct areas based on structural connectivity criteria is of widespread interest in neuroscience. This paper presents a groupwise connectivity-based parcellation framework for the whole cortical surface using a new high quality diffusion dataset of 79 healthy subjects. Our approach performs gyrus by gyrus to parcellate the whole human cortex. The main originality of the method is to compress for each gyrus the connectivity profiles used for the clustering without any anatomical prior information. This step takes into account the interindividual cortical and connectivity variability. To this end, we consider intersubject high density connectivity areas extracted using a surface-based watershed algorithm. A wide validation study has led to a fully automatic pipeline which is robust to variations in data preprocessing (tracking type, cortical mesh characteristics and boundaries of initial gyri), data characteristics (including number of subjects), and the main algorithmic parameters. A remarkable reproducibility is achieved in parcellation results for the whole cortex, leading to clear and stable cortical patterns. This reproducibility has been tested across non-overlapping subgroups and the validation is presented mainly on the pre- and postcentral gyri. PMID- 26849424 TI - A local Echo State Property through the largest Lyapunov exponent. AB - Echo State Networks are efficient time-series predictors, which highly depend on the value of the spectral radius of the reservoir connectivity matrix. Based on recent results on the mean field theory of driven random recurrent neural networks, enabling the computation of the largest Lyapunov exponent of an ESN, we develop a cheap algorithm to establish a local and operational version of the Echo State Property. PMID- 26849423 TI - The application of a new sampling theorem for non-bandlimited signals on the sphere: Improving the recovery of crossing fibers for low b-value acquisitions. AB - Recent development in sampling theory now allows the sampling and reconstruction of certain non-bandlimited functions on the sphere, namely a sum of weighted Diracs. Because the signal acquired in diffusion Magnetic Resonance Imaging (dMRI) can be modeled as the convolution between a sampling kernel and two dimensional Diracs defined on the sphere, these advances have great potential in dMRI. In this work, we introduce a local reconstruction method for dMRI based on a new sampling theorem for non-bandlimited signals on the sphere. This new algorithm, named Spherical Finite Rate of Innovation (SFRI), is able to recover fibers crossing at very narrow angles with little dependence on the b-value. Because of its parametric formulation, SFRI can distinguish crossing fibers even when using a DTI-like acquisition (~32 directions). This opens new perspective for low b-value and low number of gradient directions diffusion acquisitions and tractography studies. We evaluate the angular resolution of SFRI using state of the art synthetic data and compare its performance using in-vivo data. Our results show that, at low b-values, SFRI recovers crossing fibers not identified by constrained spherical deconvolution. We also show that low b-value results obtained using SFRI are similar to those obtained with constrained spherical deconvolution at a higher b-value. PMID- 26849425 TI - Photochemical Properties and Reactivity of a Ru Compound Containing an NAD/NADH Functionalized 1,10-Phenanthroline Ligand. AB - An NAD/NADH-functionalized ligand, benzo[b]pyrido[3,2-f][1,7]-phenanthroline (bpp), was newly synthesized. A Ru compound containing the bpp ligand, [Ru(bpp)(bpy)2](2+), underwent 2e(-) and 2H(+) reduction, generating the NADH form of the compound, [Ru(bppHH)(bpy)2](2+), in response to visible light irradiation in CH3CN/TEA/H2O (8/1/1). The UV-vis and fluorescent spectra of both [Ru(bpp)(bpy)2](2+) and [Ru(bppHH)(bpy)2](2+) resembled the spectra of [Ru(bpy)3](2+). Both complexes exhibited strong emission, with quantum yields of 0.086 and 0.031, respectively; values that are much higher than those obtained from the NAD/NADH-functionalized complexes [Ru(pbn)(bpy)2](2+) and [Ru(pbnHH)(bpy)2](2+) (pbn = (2-(2-pyridyl)benzo[b]-1.5-naphthyridine, pbnHH = hydrogenated form of pbn). The reduction potential of the bpp ligand in [Ru(bpp)(bpy)2](2+) (-1.28 V vs SCE) is much more negative than that of the pbn ligand in [Ru(pbn)(bpy)2](2+) (-0.74 V), although the oxidation potentials of bppHH and pbnHH are essentially equal (0.95 V). These results indicate that the electrochemical oxidation of the dihydropyridine moiety in the NADH-type ligand was independent of the pi system, including the Ru polypyridyl framework. [Ru(bppHH)(bpy)2](2+) allowed the photoreduction of oxygen, generating H2O2 in 92% yield based on [Ru(bppHH)(bpy)2](2+). H2O2 production took place via singlet oxygen generated by the energy transfer from excited [Ru(bppHH)(bpy)2](2+) to triplet oxygen. PMID- 26849426 TI - Comparison of single photon emission CT (SPECT) with SPECT/CT imaging in preoperative localization of parathyroid adenomas: A cost-effectiveness analysis. AB - BACKGROUND: Controversy exists regarding the superiority of single photon emission CT (SPECT)/CT over SPECT for preoperative localization of parathyroid adenomas in primary hyperparathyroidism (PHPT), as well as the cost effectiveness. METHODS: A retrospective review was undertaken of patients undergoing surgery for PHPT from January 2009 to August 2014. Ultrasound and SPECT (ultrasound-SPECT) or SPECT/CT (ultrasound-SPECT/CT) were performed for each patient. Sensitivity and positive predictive value (PPV) of each modality were calculated. Cost-effectiveness was determined by an incremental cost effectiveness ratio (ICER) analysis. RESULTS: Two hundred fifty-nine patients with 266 parathyroid adenomas were included in the study. Lateralization sensitivity and PPV of ultrasound-SPECT were 85.1% and 98.2%, respectively. The lateralization sensitivity and PPV of ultrasound-SPECT/CT were 86.9% and 99.4%, respectively. A cost of $2499.22 (CAD) per additional parathyroid adenoma detection by ultrasound-SPECT/CT was determined from the ICER analysis. CONCLUSION: Similar sensitivities and PPVs were observed between ultrasound-SPECT and ultrasound-SPECT/CT in preoperatively lateralizing parathyroid adenomas, with relatively equivalent cost-effectiveness. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2062-E2065, 2016. PMID- 26849427 TI - The safety and efficacy of safinamide mesylate for the treatment of Parkinson's disease. AB - Safinamide (brand name Xadago(r), Zambon S.p.A) is a third-generation reversible MAO-B inhibitor, which also blocks sodium voltage-sensitive channels and modulates stimulated release of glutamate. Safinamide was recently licensed by EMA for the treatment of PD as add-on therapy to a stable dose of levodopa alone or in combination with other PD medicinal products in mid-to advanced-stage fluctuating patients. It is also under review by the US FDA. Studies in 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys and 6OHDA-lesioned rats suggest antiparkinsonian efficacy and antidyskinesic effects. Randomized, double-blind, placebo-controlled trials have shown efficacy for the treatment of motor symptoms in stable PD patients on dopamine agonists and in fluctuating PD patients on levodopa. Significant improvement in daily ON time was also observed in the latter. This effect was maintained for at least 2 years in double-blind conditions and, interestingly, without significant worsening of dyskinesia. Clinical studies have not detected any specific safety issue other than those already known with MAO-B inhibitors. PMID- 26849430 TI - A survey of anthropometry and physical accommodation in ergonomics curricula. AB - The size and shape of users are an important consideration for many products and environments. Designers and engineers in many disciplines must often accommodate these attributes to meet objectives such as fit and safety. When practitioners have academic training in addressing these issues, it is typically through courses in Human Factors/Ergonomics (HF/E). This paper investigates education related to physical accommodation and offers suggestions for improvement. A survey was conducted wherein 21 instructors at 18 universities in the United States provided syllabi for 29 courses, which were analysed to determine topics related to anthropometry and resources used for the courses. The results show that within the U.S., anthropometry is covered in the majority of courses discussing physical ergonomics, but important related concepts were often omitted (e.g., digital human modelling, multivariate accommodation and variability across global populations). Curricula could be improved by incorporating more accurate anthropometry, multivariate problems and interactive online tools. PRACTITIONER SUMMARY: This paper describes a study investigating collegiate ergonomics courses within the U.S. in the area of physical accommodation. Course schedules and texts were studied for their treatment of several topics related to accommodating the spatial requirements (anthropometry) of users. Recommendations are made for improving course curricula. PMID- 26849429 TI - MicroRNA-27b Regulates Mitochondria Biogenesis in Myocytes. AB - MicroRNAs (miRNAs) are small, non-coding RNAs that affect the post transcriptional regulation of various biological pathways. To date, it is not fully understood how miRNAs regulate mitochondrial biogenesis. This study aimed at the identification of the role of miRNA-27b in mitochondria biogenesis. The mitochondria content in C2C12 cells was significantly increased during myogenic differentiation and accompanied by a marked decrease of miRNA-27b expression. Furthermore, the expression of the predicted target gene of miRNA-27b, forkhead box j3 (Foxj3), was also increased during myogenic differentiation. Luciferase activity assays confirmed that miRNA-27b directly targets the 3'-untranslated region (3'-UTR) of Foxj3. Overexpression of miRNA-27b provoked a decrease of mitochondria content and diminished expression of related mitochondrial genes and Foxj3 both at mRNA and protein levels. The expression levels of downstream genes of Foxj3, such as Mef2c, PGC1alpha, NRF1 and mtTFA, were also decreased in C2C12 cells upon overexpression of miRNA-27b. These results suggested that miRNA-27b may affect mitochondria biogenesis by down-regulation of Foxj3 during myocyte differentiation. PMID- 26849428 TI - Site-Specific Internal Motions in GB1 Protein Microcrystals Revealed by 3D 2H-13C 13C Solid-State NMR Spectroscopy. AB - (2)H quadrupolar line shapes deliver rich information about protein dynamics. A newly designed 3D (2)H-(13)C-(13)C solid-state NMR magic angle spinning (MAS) experiment is presented and demonstrated on the microcrystalline beta1 immunoglobulin binding domain of protein G (GB1). The implementation of (2)H (13)C adiabatic rotor-echo-short-pulse-irradiation cross-polarization (RESPIRATION CP) ensures the accuracy of the extracted line shapes and provides enhanced sensitivity relative to conventional CP methods. The 3D (2)H-(13)C-(13)C spectrum reveals (2)H line shapes for 140 resolved aliphatic deuterium sites. Motional-averaged (2)H quadrupolar parameters obtained from the line-shape fitting identify side-chain motions. Restricted side-chain dynamics are observed for a number of polar residues including K13, D22, E27, K31, D36, N37, D46, D47, K50, and E56, which we attribute to the effects of salt bridges and hydrogen bonds. In contrast, we observe significantly enhanced side-chain flexibility for Q2, K4, K10, E15, E19, N35, N40, and E42, due to solvent exposure and low packing density. T11, T16, and T17 side chains exhibit motions with larger amplitudes than other Thr residues due to solvent interactions. The side chains of L5, V54, and V29 are highly rigid because they are packed in the core of the protein. High correlations were demonstrated between GB1 side-chain dynamics and its biological function. Large-amplitude side-chain motions are observed for regions contacting and interacting with immunoglobulin G (IgG). In contrast, rigid side chains are primarily found for residues in the structural core of the protein that are absent from protein binding and interactions. PMID- 26849431 TI - Age-Related Decline of Neutrophilic Inflammation Is Associated with Better Postoperative Prognosis in Non-eosinophilic Nasal Polyps. AB - BACKGROUND: Innate and adaptive immune responses change with increasing age and affect the course of diseases. Previous study investigated immunologic alteration in Western nasal polyps (NP) which is mostly eosinophilic. However, there are no reports regarding age-related immune changes of non-eosinophilic NP (NE-NP) which is a predominant subtype in Asian population. METHODS: A total of 153 subjects, including 20 with control, 63 with chronic rhinosinusitis (CRS) without NP (CRSsNP), and 70 with CRS with NP were enrolled. Age-related changes in computed tomography (CT), cytokines and clinical information were investigated. Tissue samples were analyzed for protein levels of IL-5, IL-17A, IL-23, interferon (IFN) gamma, CCL-11, and CXCL-8, using Luminex immunoassay and for mRNA expression levels of interleukin (IL)-5, IL-17A, IL-23p19, IFN-gamma, CCL-11, CXCL-1, CXCL 2, CXCL-8, and CXCR2 by quantitative RT-PCR. Immunohistochemistry (IHC) was performed for the number of inflammatory cells. RESULTS: We observed that Lund Mackay CT scores decreased with age in NE-NP. The number of human neutrophil elastase-positive cells and myeloperoxidase gene expression decreased in older patients with NE-NP, but not in control subjects, CRSsNP, and E-NP. Neutrophil associated cytokines including IL-17A and IL-23, were negatively correlated with age in NE-NP at the protein and mRNA levels. Additionally, the expression of CXCR2, a receptor for CXCL-1 and CXCL-2, was decreased with age in NE-NP. However, there were no age-related changes in blood neutrophil count, and neutrophil-recruiting chemokines such as CXCL-1, CXCL-2, and CXCL-8. Elderly NE NP patients showed better endoscopic scores at 12 months after surgery compared with the non-elderly. CONCLUSION: Age-related decline in neutrophil inflammation may favorably affect postoperative results in elderly patients with NE-NP. PMID- 26849433 TI - Cranial Anatomy and Palaeoneurology of the Archosaur Riojasuchus tenuisceps from the Los Colorados Formation, La Rioja, Argentina. AB - Riojasuchus tenuisceps Bonaparte 1967 is currently known from four specimens, including two complete skulls, collected in the late 1960s from the upper levels of the Los Colorados Formation (Late Triassic), La Rioja, Argentina. Computed tomography (CT) scans of the skulls of the holotype and a referred specimen of Riojasuchus tenuisceps and the repreparation of the latter allows recognition of new features for a detailed analysis of its cranial anatomy and its comparison with a wide variety of other archosauriform taxa. The diagnosis of Riojasuchus tenuisceps is emended and two autapomorphies are identified on the skull: (1) a deep antorbital fossa with its anterior and ventral edges almost coinciding with the same edges of the maxilla itself and (2) a suborbital fenestra equal in size to the palatine-pterygoid fenestra. Also, the first digital 3D reconstruction of the encephalon of Riojasuchus tenuisceps was carried out to study its neuroanatomy, showing a shape and cranial nerve disposition consistent to that of other pseudosuchians. PMID- 26849432 TI - Voltage-Gated K+ Channel, Kv3.3 Is Involved in Hemin-Induced K562 Differentiation. AB - Voltage-gated K+ (Kv) channels are well known to be involved in cell proliferation. However, even though cell proliferation is closely related to cell differentiation, the relationship between Kv channels and cell differentiation remains poorly investigated. This study demonstrates that Kv3.3 is involved in K562 cell erythroid differentiation. Down-regulation of Kv3.3 using siRNA-Kv3.3 increased hemin-induced K562 erythroid differentiation through decreased activation of signal molecules such as p38, cAMP response element-binding protein, and c-fos. Down-regulation of Kv3.3 also enhanced cell adhesion by increasing integrin beta3 and this effect was amplified when the cells were cultured with fibronectin. The Kv channels, or at least Kv3.3, appear to be associated with cell differentiation; therefore, understanding the mechanisms of Kv channel regulation of cell differentiation would provide important information regarding vital cellular processes. PMID- 26849434 TI - Correction: Rapid Diagnostic Tests for Dengue Virus Infection in Febrile Cambodian Children: Diagnostic Accuracy and Incorporation into Diagnostic Algorithms. PMID- 26849435 TI - Improved Resection and Outcome of Colon-Cancer Liver Metastasis with Fluorescence Guided Surgery Using In Situ GFP Labeling with a Telomerase-Dependent Adenovirus in an Orthotopic Mouse Model. AB - Fluorescence-guided surgery (FGS) of cancer is an area of intense development. In the present report, we demonstrate that the telomerase-dependent green fluorescent protein (GFP)-containing adenovirus OBP-401 could label colon-cancer liver metastasis in situ in an orthotopic mouse model enabling successful FGS. OBP-401-GFP-labeled liver metastasis resulted in complete resection with FGS, in contrast, conventional bright-light surgery (BLS) did not result in complete resection of the metastasis. OBP-401-FGS reduced the recurrence rate and prolonged over-all survival compared with BLS. In conclusion, adenovirus OBP-401 is a powerful tool to label liver metastasis in situ with GFP which enables its complete resection, not possible with conventional BLS. PMID- 26849437 TI - Correction: Universality of Citation Distributions for Academic Institutions and Journals. PMID- 26849436 TI - Transcriptome Profiling of Resistance to Fusarium oxysporum f. sp. conglutinans in Cabbage (Brassica oleracea) Roots. AB - Fusarium wilt caused by Fusarium oxysporum f. sp. conglutinans (FOC) is a destructive disease of Brassica crops, which results in severe yield losses. There is little information available about the mechanism of disease resistance. To obtain an overview of the transcriptome profiles in roots of R4P1, a Brassica oleracea variety that is highly resistant to fusarium wilt, we compared the transcriptomes of samples inoculated with FOC and samples inoculated with distilled water. RNA-seq analysis generated more than 136 million 100-bp clean reads, which were assembled into 62,506 unigenes (mean size = 741 bp). Among them, 49,959 (79.92%) genes were identified based on sequence similarity searches, including SwissProt (29,050, 46.47%), Gene Ontology (GO) (33,767, 54.02%), Clusters of Orthologous Groups (KOG) (14,721, 23.55%) and Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG) (12,974, 20.76%) searches; digital gene expression analysis revealed 885 differentially expressed genes (DEGs) between infected and control samples at 4, 12, 24 and 48 hours after inoculation. The DEGs were assigned to 31 KEGG pathways. Early defense systems, including the MAPK signaling pathway, calcium signaling and salicylic acid mediated hypersensitive response (SA-mediated HR) were activated after pathogen infection. SA-dependent systemic acquired resistance (SAR), ethylene (ET)- and jasmonic (JA)-mediated pathways and the lignin biosynthesis pathway play important roles in plant resistance. We also analyzed the expression of defense related genes, such as genes encoding pathogenesis-related (PR) proteins, UDP glycosyltransferase (UDPG), pleiotropic drug resistance, ATP-binding cassette transporters (PDR-ABC transporters), myrosinase, transcription factors and kinases, which were differentially expressed. The results of this study may contribute to efforts to identify and clone candidate genes associated with disease resistance and to uncover the molecular mechanism underlying FOC resistance in cabbage. PMID- 26849439 TI - Differences between Total Intravenous Anesthesia and Inhalation Anesthesia in Free Flap Surgery of Head and Neck Cancer. AB - BACKGROUND: Many studies have evaluated risk factors associated with complications after free flap surgery, but these studies did not evaluate the impact of anesthesia management. The goal of the current study was to evaluate the differences between patients who received inhalation and total intravenous anesthesia (TIVA) in free flap surgery. METHODS: One hundred and fifty-six patients who underwent free flap surgery for head and neck cancer were retrospectively divided into the TIVA (96 patients) and the inhalation group (87 patients). Perioperative hemodynamic data and postoperative medical complications were determined by documented medical records. RESULTS: Ninety-six patients in the TIVA group were compared with 87 patients who received inhalation anesthesia. There were no differences in gender, age, classification of physical status based on American Society for Anesthesiologists (ASA) score, and cormobidities between the two groups. Patients in the TIVA group required less perioperative crystalloid (4172.46 +/- 1534.95 vs. 5183.91 +/- 1416.40 ml, p < 0.0001) and colloid (572.46 +/- 335.14 vs. 994.25 +/- 434.65 ml, p < 0.0001) to maintain hemodynamic stability. Although the mean anesthesia duration was shorter in the TIVA group (11.02 +/- 2.84 vs. 11.70+/- 1.96 hours, p = 0.017), the blood loss was similar between groups (p = 0.71). There was no difference in surgical complication rate, but patients in the TIVA group developed fewer pulmonary complications (18 vs. 47, p = 0.0008). After multivariate regression, patients in the TIVA group had a significantly reduced risk of pulmonary complication compared with the inhalation group (Odds ratio 0.41, 95% CI 0.18-0.92). CONCLUSIONS: Total intravenous anesthesia was associated with significantly fewer pulmonary complications in patients who received free flap reconstruction. PMID- 26849440 TI - Community Structure of Macrobiota and Environmental Parameters in Shallow Water Hydrothermal Vents off Kueishan Island, Taiwan. AB - Hydrothermal vents represent a unique habitat in the marine ecosystem characterized with high water temperature and toxic acidic chemistry. Vents are distributed at depths ranging from a few meters to several thousand meters. The biological communities of shallow-water vents have, however, been insufficiently studied in most biogeographic areas. We attempted to characterize the macrofauna and macroflora community inhabiting the shallow-water vents off Kueishan Island, Taiwan, to identify the main abiotic factors shaping the community structure and the species distribution. We determined that positively buoyant vent fluid exhibits a more pronounced negative impact to species on the surface water than on the bottom layer. Species richness increased with horizontal distance from the vent, and continuing for a distance of 2000 m, indicating that the vent fluid may exert a negative impact over several kilometers. The community structure off Kueishan Island displayed numerous transitions along the horizontal gradient, which were broadly congruent with changes in environmental conditions. Combination of variation in Ca2+, Cl-, temperature, pH and depth were revealed to show the strongest correlation with the change in benthic community structure, suggesting multiple factors of vent fluid were influencing the associated fauna. Only the vent crabs of Kueishan Island may have an obligated relationship with vents and inhabit the vent mouths because other fauna found nearby are opportunistic taxa that are more tolerant to acidic and toxic environments. PMID- 26849438 TI - Clinical Guidelines for Management of Bone Health in Rett Syndrome Based on Expert Consensus and Available Evidence. AB - OBJECTIVES: We developed clinical guidelines for the management of bone health in Rett syndrome through evidence review and the consensus of an expert panel of clinicians. METHODS: An initial guidelines draft was created which included statements based upon literature review and 11 open-ended questions where literature was lacking. The international expert panel reviewed the draft online using a 2-stage Delphi process to reach consensus agreement. Items describe the clinical assessment of bone health, bone mineral density assessment and technique, and pharmacological and non-pharmacological interventions. RESULTS: Agreement was reached on 39 statements which were formulated from 41 statements and 11 questions. When assessing bone health in Rett syndrome a comprehensive assessment of fracture history, mutation type, prescribed medication, pubertal development, mobility level, dietary intake and biochemical bone markers is recommended. A baseline densitometry assessment should be performed with accommodations made for size, with the frequency of surveillance determined according to individual risk. Lateral spine x-rays are also suggested. Increasing physical activity and initiating calcium and vitamin D supplementation when low are the first approaches to optimizing bone health in Rett syndrome. If individuals with Rett syndrome meet the ISCD criterion for osteoporosis in children, the use of bisphosphonates is recommended. CONCLUSION: A clinically significant history of fracture in combination with low bone densitometry findings is necessary for a diagnosis of osteoporosis. These evidence and consensus-based guidelines have the potential to improve bone health in those with Rett syndrome, reduce the frequency of fractures, and stimulate further research that aims to ameliorate the impacts of this serious comorbidity. PMID- 26849441 TI - Anatomical Variations in the Sinoatrial Nodal Artery: A Meta-Analysis and Clinical Considerations. AB - BACKGROUND AND OBJECTIVE: The sinoatrial nodal artery (SANa) is a highly variable vessel which supplies blood to the sinoatrial node (SAN). Due to its variability and susceptibility to iatrogenic injury, our study aimed to assess the anatomy of the SANa and determine the prevalence of its anatomical variations. STUDY DESIGN: An extensive search of major electronic databases was performed to identify all articles reporting anatomical data on the SANa. No lower date limit or language restrictions were applied. Anatomical data regarding the artery were extracted and pooled into a meta-analysis. RESULTS: Sixty-six studies (n = 21455 hearts) were included in the meta-analysis. The SANa usually arose as a single vessel with a pooled prevalence of 95.5% (95%CI:93.6-96.9). Duplication and triplication of the artery were also observed with pooled prevalence of 4.3% (95%CI:2.8-6.0) and 0.3% (95%CI:0-0.7), respectively. The most common origin of the SANa was from the right coronary artery (RCA), found in 68.0% (95%CI:55.6-68.9) of cases, followed by origin from the left circumflex artery, and origin from the left coronary artery with pooled prevalence of 22.1% (95%CI:15.0-26.2) and 2.7 (95%CI:0.7-5.2), respectively. A retrocaval course of the SANa was the most common course of the artery with a pooled prevalence of 47.1% (95%CI:36.0-55.5). The pooled prevalence of an S-shaped SANa was 7.6% (95%CI:2.9-14.1). CONCLUSIONS: The SANa is most commonly reported as a single vessel, originating from the RCA, and taking a retrocaval course to reach the SAN. Knowledge of high risk anatomical variants of the SANa, such as an S-shaped artery, must be taken into account by surgeons to prevent iatrogenic injuries. Specifically, interventional or cardiosurgical procedures, such as the Cox maze procedure for atrial fibrillation, open heart surgeries through the right atrium or intraoperative cross-clamping or dissection procedures during mitral valve surgery using the septal approach can all potentiate the risk for injury in the setting of high risk morphological variants of the SANa. PMID- 26849442 TI - Direct Observation of Treatment Provided by a Family Member as Compared to Non Family Member among Children with New Tuberculosis: A Pragmatic, Non-Inferiority, Cluster-Randomized Trial in Gujarat, India. AB - BACKGROUND: The World Health Organization recommends direct observation of treatment (DOT) to support patients with tuberculosis (TB) and to ensure treatment completion. As per national programme guidelines in India, a DOT provider can be anyone who is acceptable and accessible to the patient and accountable to the health system, except a family member. This poses challenges among children with TB who may be more comfortable receiving medicines from their parents or family members than from unfamiliar DOT providers. We conducted a non inferiority trial to assess the effect of family DOT on treatment success rates among children with newly diagnosed TB registered for treatment during June September 2012. METHODS: We randomly assigned all districts (n = 30) in Gujarat to the intervention (n = 15) or usual-practice group (n = 15). Adult family members in the intervention districts were given the choice to become their child's DOT provider. DOT was provided by a non-family member in the usual practice districts. Using routinely collected clinic-based TB treatment cards, we compared treatment success rates (cured and treatment completed) between the two groups and the non-inferiority limit was kept at 5%. RESULTS: Of 624 children with newly diagnosed TB, 359 (58%) were from intervention districts and 265 (42%) were from usual-practice districts. The two groups were similar with respect to baseline characteristics including age, sex, type of TB, and initial body weight. The treatment success rates were 344 (95.8%) and 247 (93.2%) (p = 0.11) among the intervention and usual-practice groups respectively. CONCLUSION: DOT provided by a family member is not inferior to DOT provided by a non-family member among new TB cases in children and can attain international targets for treatment success. TRIAL REGISTRATION: Clinical Trials Registry-India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2015/09/006229. PMID- 26849444 TI - Correction: The Global Health Impact Index: Promoting Global Health. PMID- 26849443 TI - Missense Mutations Allow a Sequence-Blind Mutant of SpoIIIE to Successfully Translocate Chromosomes during Sporulation. AB - SpoIIIE directionally pumps DNA across membranes during Bacillus subtilis sporulation and vegetative growth. The sequence-reading domain (gamma domain) is required for directional DNA transport, and its deletion severely impairs sporulation. We selected suppressors of the spoIIIEDeltagamma sporulation defect. Unexpectedly, many suppressors were intragenic missense mutants, and some restore sporulation to near-wild-type levels. The mutant proteins are likely not more abundant, faster at translocating DNA, or sequence-sensitive, and rescue does not involve the SpoIIIE homolog SftA. Some mutants behave differently when co expressed with spoIIIEDeltagamma, consistent with the idea that some, but not all, variants may form mixed oligomers. In full-length spoIIIE, these mutations do not affect sporulation, and yet the corresponding residues are rarely found in other SpoIIIE/FtsK family members. The suppressors do not rescue chromosome translocation defects during vegetative growth, indicating that the role of the gamma domain cannot be fully replaced by these mutations. We present two models consistent with our findings: that the suppressors commit to transport in one arbitrarily-determined direction or delay spore development. It is surprising that missense mutations somehow rescue loss of an entire domain with a complex function, and this raises new questions about the mechanism by which SpoIIIE pumps DNA and the roles SpoIIIE plays in vivo. PMID- 26849446 TI - Prioritizing health services research: an economic perspective. AB - INTRODUCTION: Given limited resources policymakers need to decide about how much and in what areas of health services research (HSR) to invest. The purpose of this study is to provide guidance for priority setting of HSR projects based on economic theory. METHODS: The conceptual analysis starts from the premise that competition in health care is valuable-a position that seems to predominate among Western policymakers. The principle of competition rests on economic theory and, in particular, its branch of welfare economics. RESULTS: Based on economic theory, the role of HSR is to detect and alleviate information asymmetry, negative externalities, and harm caused by competition and inappropriate incentives for competition. A hierarchy of HSR projects is provided; following the ethical principle of harm ('do not harm'), the detection and prevention of harm would receive highest priority among HSR projects. CONCLUSIONS: Agreeing that competition is valuable in achieving efficiency and quality of care (and therefore agreeing to the assumptions of economic theory) implies accepting the role of HSR in detecting market failure and the HSR hierarchy as suggested. Disagreement would require an alternative coherent concept of improving efficiency and quality of care. PMID- 26849445 TI - Comparison of Three Screening Test Kits for G6PD Enzyme Deficiency: Implications for Its Use in the Radical Cure of Vivax Malaria in Remote and Resource-Poor Areas in the Philippines. AB - OBJECTIVE: We evaluated a battery of Glucose-6-Phosphate Dehydrogenase diagnostic point-of-care tests (PoC) to assess the most suitable product in terms of performance and operational characteristics for remote areas. METHODS: Samples were collected in Puerto Princesa City, Palawan, Philippines and tested for G6PD deficiency with a fluorescent spot test (FST; Procedure 203, Trinity Biotech, Ireland), the semiquantitative WST8/1-methoxy PMS (WST; Dojindo, Japan) and the Carestart G6PD Rapid Diagnostic Test (CSG; AccessBio, USA). Results were compared to spectrophotometry (Procedure 345, Trinity Biotech, Ireland). Sensitivity and specificity were calculated for each test with cut-off activities of 10%, 20%, 30% and 60% of the adjusted male median. RESULTS: The adjusted male median was 270.5 IU/10(12) RBC. FST and WST were tested on 621 capillary blood samples, the CSG was tested on venous and capillary blood on 302 samples. At 30% G6PD activity, sensitivity for the FST was between 87.7% (95%CI: 76.8% to 93.9%) and 96.5% (95%CI: 87.9% to 99.5%) depending on definition of intermediate results; the WST was 84.2% (95%CI: 72.1% to 92.5%); and the CSG was between 68.8% (95%CI: 41.3% to 89.0%) and 93.8% (95%CI: 69.8% to 99.8%) when the test was performed on capillary or venous blood respectively. Sensitivity of FST and CSG (tested with venous blood) were comparable (p>0.05). The analysis of venous blood samples by the CSG yielded significantly higher results than FST and CSG performed on capillary blood (p<0.05). Sensitivity of the CSG varied depending on source of blood used (p<0.05). CONCLUSION: The operational characteristics of the CSG were superior to all other test formats. Performance and operational characteristics of the CSG performed on venous blood suggest the test to be a good alternative to the FST. PMID- 26849448 TI - Psychopathic teamwork: lessons learned from recent terrorist attacks. PMID- 26849447 TI - Differences in Looking at Own- and Other-Race Faces Are Subtle and Analysis Dependent: An Account of Discrepant Reports. AB - The Other-Race Effect (ORE) is the robust and well-established finding that people are generally poorer at facial recognition of individuals of another race than of their own race. Over the past four decades, much research has focused on the ORE because understanding this phenomenon is expected to elucidate fundamental face processing mechanisms and the influence of experience on such mechanisms. Several recent studies of the ORE in which the eye-movements of participants viewing own- and other-race faces were tracked have, however, reported highly conflicting results regarding the presence or absence of differential patterns of eye-movements to own- versus other-race faces. This discrepancy, of course, leads to conflicting theoretical interpretations of the perceptual basis for the ORE. Here we investigate fixation patterns to own- versus other-race (African and Chinese) faces for Caucasian participants using different analysis methods. While we detect statistically significant, though subtle, differences in fixation pattern using an Area of Interest (AOI) approach, we fail to detect significant differences when applying a spatial density map approach. Though there were no significant differences in the spatial density maps, the qualitative patterns matched the results from the AOI analyses reflecting how, in certain contexts, Area of Interest (AOI) analyses can be more sensitive in detecting the differential fixation patterns than spatial density analyses, due to spatial pooling of data with AOIs. AOI analyses, however, also come with the limitation of requiring a priori specification. These findings provide evidence that the conflicting reports in the prior literature may be at least partially accounted for by the differences in the statistical sensitivity associated with the different analysis methods employed across studies. Overall, our results suggest that detection of differences in eye-movement patterns can be analysis-dependent and rests on the assumptions inherent in the given analysis. PMID- 26849449 TI - Comparison of single-spot technique and RGB imaging for erythema index estimation. AB - A commercially available point measurement device, the Mexameter((r)), and an experimental RGB imaging prototype device were used for erythema index estimation of 50 rosacea patients by analysing the level of skin redness on the forehead, both cheeks and both sides of a nose. Results are compared with Clinician's Erythema Assessment (CEA) values given by two dermatologists. The Mexameter uses 568 nm and 660 nm LEDs and a photodetector for estimation of erythema index, while the used prototype device acquired RGB images at 460 nm, 530 nm and 665 nm LED illumination. Several erythema index estimation algorithms were compared to determine which one gives the best contrast between increased erythema and normal skin. The erythema index estimations and CEA values correlated much better for the RGB imaging data than for those obtained by the conventional Mexameter technique that is widely used by dermatologists and in clinical trials. In result, we propose an erythema index estimation approach that represents increased erythema with higher accuracy than other available methods. PMID- 26849450 TI - Beat Rate Variability in Murine Embryonic Stem Cell-Derived Cardiomyocytes: Effect of Antiarrhythmic Drugs. AB - BACKGROUND/AIMS: Heart rate variability (HRV) refers to the fluctuation of the time interval between consecutive heartbeats in humans. It has recently been discovered that cardiomyocytes derived from human embryonic and induced pluripotent stem cells show beat rate variability (BRV) that is similar to the HRV in humans. In the present study, clinical aspects of HRV were transferred to an in vitro model. The aims of the study were to explore the BRV in murine embryonic stem cell (mESC)-derived cardiomyocytes and to demonstrate the influence of antiarrhythmic drugs on BRV as has been shown in clinical trials previously. METHODS: The Microelectrode Array (MEA) technique was used to perform short-term recordings of extracellular field potentials (FPs) of spontaneously beating cardiomyocytes derived from mESCs (D3 cell line, alphaPig-44). Offline analysis was focused on time domain and nonlinear methods. RESULTS: The Poincare Plot analysis of measurements without pharmacological intervention revealed that three different shapes of scatter plots occurred most frequently. Comparable shapes have been described in clinical studies before. The antiarrhythmic drugs Ivabradine, Verapamil and Sotalol augmented BRV, whereas Flecainide decreased BRV parameters at low concentrations (SDSD 79.0 +/- 8.7% of control at 10(-9) M, p < 0.05) and increased variability measures at higher concentrations (SDNN 258.8 +/- 42.7% of control at 10(-5) M, p < 0.05). Amiodarone and Metoprolol did not alter BRV significantly. CONCLUSIONS: Spontaneously beating cardiomyocytes derived from mESCs showed BRV that appears to be similar to the HRV known from humans. Antiarrhythmic drugs affected BRV parameters similar to clinical observations. Therefore, our study demonstrates that this in vitro model can contribute to a better understanding of electrophysiological properties of mESC-derived cardiomyocytes and might serve as a valuable tool for drug safety screening. PMID- 26849451 TI - Formation and Dynamics of Ion-Stabilized Gas Nanobubble Phase in the Bulk of Aqueous NaCl Solutions. AB - Ion-stabilized gas nanobubbles (the so-termed "bubstons") and their clusters are investigated in bulk aqueous solutions of NaCl at different ion concentrations by four independent laser diagnostic methods. It turned out that in the range of NaCl concentration 10(-6) < C < 1 M the radius of bubston remains virtually unchanged at a value of 100 nm. Bubstons and their clusters are a thermodynamically nonequilibrium phase, which has been demonstrated in experiments with magnetic stirrer at different stirring rates. Different regimes of the bubston generation, resulting from various techniques of processing the liquid samples, were explored. PMID- 26849452 TI - Access to the 2H-Tetrahydro-4,6-dioxo-1,2-oxazine Ring System from Nitrone via a Tandem Nucleophilic Addition and Transesterification Reaction. AB - A general and efficient synthesis of the 2H-tetrahydro-4,6-dioxo-1,2-oxazine ring system through a tandem nucleophilic addition and transesterification reaction is described. The reaction is highly functional-group-tolerant and proceeds under mild conditions, affording the corresponding products in good to excellent yields. This method represents the first general synthetic route to access this heterocyclic scaffold, which exists in the complex natural products alchivemycin A and B with significant antibiotic activities. PMID- 26849453 TI - Prevalence of Diabetes and Diabetic Neuropathy in Qena Governorate: Population Based Survey. AB - BACKGROUND: No previous study was done to estimate the prevalence of diabetic neuropathy (DN) in Arabic countries. The aim of this study was to estimate the prevalence of DN and its characteristics in Qena governorate. MATERIAL AND METHODS: This is a random sampling of 10 study areas, involving 9,303 inhabitants; 51.1% men and 48.9% women were recruited. There were 57.3% urban residents and 42.7% rural residents. Patients were diagnosed using a screening questionnaire for diabetes mellitus (DM) as well as for DN in addition to measuring blood sugar in suspected cases. All positive cases were referred to Qena University Hospital and were subjected to full clinical, electrophysiological and laboratory investigations. RESULTS: Out of 9,303 people screened, 837 were diabetic giving prevalence 8.99% of the population. Eight hundred eleven had type II DM and 26 cases had type I giving prevalence of 8.7 and 0.3%, respectively. One hundred fifty-five out of 837 (18.5%) diabetic patients had evidence of DN with prevalence rate being 1.7% of the total population. Diabetic polyneuropathy was the commonest type with prevalence 1.5%. The prevalence of DN was higher in women than in men. Rural residents had significantly higher prevalence of DN compared to urban residents (1.9 vs. 1.4) and illiterate population more than educated (5.8 vs. 1.2). CONCLUSION: The overall crude prevalence rate of DM and DN is nearly the same as in European countries and lower than that in other Arabic countries. PMID- 26849454 TI - Duane retraction syndrome in a patient with Duchenne muscular dystrophy. AB - PURPOSE: We describe the clinical features of a boy with bilateral Duane retraction syndrome (DRS), Duchenne muscular dystrophy (DMD), and other medical problems. METHODS: The child was followed-up for five years; his chart was reviewed, including the results of a muscle biopsy and genetic testing. Multiplex ligation-dependent probe amplification (MLPA) was used to interrogate deletions/duplications in the dystrophin gene. RESULTS: The proband had bilateral DRS with otherwise normal ocular motility; he also had developmental delay, mild mental retardation, and seizures. Clinical diagnosis of DMD included progressive proximal weakness, highly elevated creatine kinase levels, and a muscle biopsy showing significant dystrophic changes including contracted, degenerative, and regenerative fibers, and negative dystrophin immunostaining. MLPA documented duplication of exons 3 and 4 of the dystrophin gene. CONCLUSIONS: This boy is the third patient to be reported with DRS and DMD, the second with bilateral DRS and the only one with other neurologic features. Mutated dystrophin is present in extraocular muscles and in the central nervous system (CNS) in DMD, leaving open the question of whether this co-occurrence is the result of the genetic muscle abnormality, CNS effects caused by dystrophin mutations, or chance. PMID- 26849455 TI - Remission of human immunodeficiency virus-related lymphoma in association with immune reconstitution on anti-retroviral therapy, without chemotherapy. PMID- 26849456 TI - Abdominal obesity and hip fracture: results from the Nurses' Health Study and the Health Professionals Follow-up Study. AB - Abdominal obesity might increase fracture risk. We studied the prospective associations between waist circumference, waist-to-hip ratio, and hip fracture. The indicators of abdominal obesity were associated with increased hip fracture risk in women, but not in men. The increased risk was restricted to women with low physical activity. INTRODUCTION: Low weight is an established risk factor for osteoporosis and hip fracture. However, the association between fat tissue, muscle, and bone is complex, and abdominal obesity might increase fracture risk. We studied the prospective associations between indicators of abdominal obesity and hip fracture in two large US cohorts. METHODS: At baseline in 1986 and through biennial follow-up, information on hip fracture and potential risk factors was collected in 61,677 postmenopausal women and 35,488 men above age 50. Waist and hip circumferences were reported at baseline and updated twice. RESULTS: During follow-up, 1168 women and 483 men sustained a hip fracture. After controlling for known risk factors, there was a significant association in women between increasing waist circumference and hip fracture (RR per 10-cm increase 1.13 (95 % CI 1.04-1.23) and between increasing waist-to-hip ratio and hip fracture (RR per 0.1 unit increase 1.14 (95 % CI 1.04-1.23), but these associations were not seen in men. In women, both measures interacted with physical activity. Those in the highest (>=0.90) versus lowest (<0.75) category of waist-to-hip ratio had increased risk of hip fracture if their activity was less than the population median (RR = 1.61, 95 % CI 1.18-2.19) but not if their activity was higher (RR = 1.00, 95 % CI 0.72-1.40). A similar pattern was found for waist circumference. CONCLUSION: Indicators of abdominal obesity were associated with increased hip fracture risk after controlling for BMI in women. The increased risk was restricted to women with low physical activity. In men, no significant associations were found. PMID- 26849457 TI - Reply. PMID- 26849458 TI - Platelets and their immune role in anti-infective immunity. PMID- 26849459 TI - Lipid Nanotube Tailored Fabrication of Uniquely Shaped Polydopamine Nanofibers as Photothermal Converters. AB - Helically coiled and linear polydopamine (PDA) nanofibers were selectively fabricated with two different types of lipid nanotubes (LNTs) that acted as templates. The obtained coiled PDA-LNT hybrid showed morphological advantages such as higher light absorbance and photothermal conversion effect compared to a linear counterpart. Laser irradiation of the coiled PDA-LNT hybrid induced a morphological change and subsequent release of the encapsulated guest molecule. In cellular experiments, the coiled PDA-LNT efficiently eliminated HeLa cells because of its strong affinity with the tumor cells. This work illustrates the first approach to construct characteristic morphologies of PDA nanofibers using LNTs as simple templates, and the coiled PDA-LNT hybrid exhibits attractive photothermal features derived from its unique coiled shape. PMID- 26849460 TI - Lumbar spine duplication: a case report. AB - Duplication of the spine is a rare malformation. A neurologically intact pediatric patient with this malformation is described here. A 6-year-old girl presented to our institution for evaluation of an asymptomatic kyphotic deformity. She denied weakness, sensory changes, and bowel or bladder complaints. Physical examination revealed mild kyphosis at the thoracolumbar junction with normal gait and neurologic function. Radiographs demonstrated duplication of the lumbar spine and sacrum. Computed tomography, MRI, and abdominal ultrasound results are reported. As she is neurologically normal, we will continue to observe this patient and intervene in the case of development of neurologic impairment or worsening kyphosis. PMID- 26849461 TI - Predictors of variability in the length of surgery of posterior instrumented arthrodesis in patients with adolescent idiopathic scoliosis. AB - The most common corrective surgery for adolescent idiopathic scoliosis (AIS) is posterior instrumented spinal fusion, which is a relatively lengthy procedure. Longer procedures are known to have higher rates of negative outcomes and higher economic costs across the surgical specialties. The purpose of this study is to identify the factors that influence the length of this operation in AIS patients. This was an institutional review board-approved, retrospective cohort study. All primary posterior instrumented arthrodesis procedures in 2011-2013 performed by three surgeons on AIS patients at a tertiary care hospital were included. Age, race, sex, BMI, Cobb angle, curve flexibility, Lenke classification, number of levels fused, number of screws used, osteotomy use, intraoperative O-arm use, and length of surgery (time from incision to closure) were obtained from the electronic medical record. Multivariable linear regression analysis was used to determine independent predictors of length of surgery, and standardized regression coefficients were calculated to compare the relative magnitude of significant variables. A total of 95 procedures were included. The average length of surgery was 375 +/- 72.7 min. The multivariable linear regression analysis contained the variables Cobb angle, number of screws used, osteotomy use, Lenke curve type, surgeon, patient age, and sex. The regression identified the number of screws used [beta=4.72, P=0.003, 95% confidence interval (CI) 1.7-7.8], osteotomy use (beta = 50.2, P = 0.004, 95% CI 16.2-84.1), Lenke type 3 curve (beta = 77.9, P = 0.001, 95% CI 31.7-174), male sex (beta=62.5, P=0.003, 95% CI 21.5-103), the Cobb angle (beta=1.04, P=0.045, 95% CI 0.02-2.1), and the surgeon (beta = 75.2, P < 0.0001, 95% CI 40-110) as independently associated with the length of surgery. The most significant factor associated with operative duration was the surgeon performing the case. We identified male sex, number of screws used, Lenke type 3 curves, osteotomy use, Cobb angle, and the surgeon variable as significantly associated with increased length of surgery in posterior arthrodesis of AIS patients. PMID- 26849462 TI - Clinical impact of second-look endoscopy after endoscopic submucosal dissection of gastric neoplasm: a multicenter prospective randomized-controlled trial. AB - OBJECTIVES: This multicenter prospective randomized-controlled study was conducted to examine the effectiveness of second-look endoscopy (SLE) implemented after performing endoscopic submucosal dissection (ESD) of gastric neoplasms and to also examine which clinical and endoscopic elements are risk factors for post ESD bleeding. PATIENTS AND METHODS: Prospective randomized studies were carried out at two tertiary medical centers. Patients were divided into a group that underwent SLE (n=110) and a group that did not undergo SLE (non-SLE, n=110). The patients' clinical characteristics, endoscopic findings, and pathologic outcomes were analyzed after ESD. RESULTS: The post-ESD bleeding rate was 4.1% and no difference was observed between the SLE group and the non-SLE group. There was no difference in age, sex, drug use, comorbidities, endoscopic findings, pathological findings, or ESD procedure time between the SLE group and the non SLE group. When the 211 patients who showed no post-ESD bleeding and nine patients who showed post-ESD bleeding were compared with each other, there was no difference in whether they underwent SLE, age, drug use, comorbidities, endoscopic findings, or pathological findings. However, the risk of occurrence of post-ESD bleeding was higher when ulcers in lesions were found (odds ratio: 12.54; P=0.03). CONCLUSION: The SLE group and the non-SLE group did not show any significant difference in post-ESD bleeding ratios among gastric neoplasm patients. It was shown that the risk of occurrence for post-ESD bleeding was higher in cases where there were ulcers in lesions than in cases where there was no ulcer in lesions. PMID- 26849463 TI - Risk factors associated with refractoriness to esophageal dilatation for benign dysphagia. AB - BACKGROUND: Benign esophageal strictures need repeated dilatations to relieve dysphagia. Literature is scarce on the risk factors for refractoriness of these strictures. AIM: This study aimed to assess the risk factors associated with refractory strictures. MATERIALS AND METHODS: This is a retrospective study of patients with benign esophageal strictures who were referred for esophageal dilatation over a period of 3 years. RESULTS: A total of 327 esophageal dilatations were performed in 103 patients; 53% of the patients reported dysphagia for liquids. Clinical success was achieved in 77% of the patients. There was a need for further dilatations in 54% of patients, being more frequent in patients with dysphagia for liquids [78 vs. 64%, P=0.008, odds ratio (OR) 1.930], in those with caustic strictures (89 vs. 70%, P=0.007, OR 3.487), and in those with complex strictures (83 vs. 70%, P=0.047, OR 2.132). Caustic strictures, peptic strictures, and complex strictures showed statistical significance in the multivariate analysis. Time until subsequent dilatations was less in patients with dysphagia for liquids (49 vs. 182 days, P<0.001), in those with peptic strictures (49 vs. 98 days, P=0.004), in those with caustic strictures (49 vs. 78 days, P=0.005), and in patients with complex strictures (47 vs. 80 days P=0.009). In multivariate analysis, further dilatations occurred earlier in patients with dysphagia for liquids [hazard ratio (HR) 1.506, P=0.004], in those with peptic strictures (HR 1.644, P=0.002), in those with caustic strictures (HR 1.581, P=0.016), and in patients with complex strictures (HR 1.408, P=0.046). CONCLUSION: Caustic, peptic, and complex strictures were associated with a greater need for subsequent dilatations. Time until subsequent dilatations was less in patients with dysphagia for liquids and in those with caustic, peptic, and complex strictures. PMID- 26849464 TI - Short article: Gastrointestinal bleeding in multiorgan failure. AB - BACKGROUND AND AIMS: Gastrointestinal bleeding (GIB) may present as complication of multiorgan failure (MOF). The study aims to analyze the reasons for the limited success of hemostasis of GIB in MOF. METHODS: Using a Markov process, GIB is modeled as one of several complications associated with multiorgan breakdown to study how the reversal of GIB affects clinical outcome. RESULTS: Although endoscopic hemostasis can delay mortality in patients with severe systemic disease, its overall influence on survival is relatively small. In patients with a time-limited transition through an acute phase of increased mortality risk secondary to MOF, endoscopic hemostasis may substantially prolong survival in absolute terms. However, its relative contribution to overall survival still remains relatively small even in the scenario of transient risk only. The benefit of endoscopy is largest, if GIB is a major contributor to morbidity and mortality in comparison with all other disease complications. CONCLUSION: Because disease outcome in MOF is ultimately determined by other complications than GIB alone, the influence of endoscopic hemostasis on patient survival often remains disappointingly small. PMID- 26849465 TI - Time pressured deprioritization of COPD in primary care: a qualitative study. AB - OBJECTIVE: To identify factors that hinder discussions regarding chronic obstructive pulmonary disease (COPD) between primary care physicians (PCPs) and their patients in Sweden. SETTING: Primary health care centres (PHCCs) in Stockholm, Sweden. SUBJECTS: A total of 59 PCPs. DESIGN: Semi-structured individual and focus-group interviews between 2012 and 2014. Data were analysed inspired by grounded theory methods (GTM). RESULTS: Time-pressured patient-doctor consultations lead to deprioritization of COPD. During unscheduled visits, deprioritization resulted from focusing only on acute health concerns, while during routine care visits, COPD was deprioritized in multi-morbid patients. The reasons PCPs gave for deprioritizing COPD are: "Not becoming aware of COPD", "Not becoming concerned due to clinical features", "Insufficient local routines for COPD care", "Negative personal attitudes and views about COPD", "Managing diagnoses one at a time", and "Perceiving a patient's motivation as low''. CONCLUSIONS: De-prioritization of COPD was discovered during PCP consultations and several factors were identified associated with time constraints and multi morbidity. A holistic consultation approach is suggested, plus extended consultation time for multi-morbid patients, and better documentation and local routines. KEY POINTS: Under-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care. A patient doctor consultation offers a key opportunity to identify and provide COPD care. Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation. Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation. Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD. PMID- 26849466 TI - Roles of Estrogen Receptor-alpha and the Coactivator MED1 During Human Endometrial Decidualization. AB - The steroid hormones 17beta-estradiol and progesterone are critical regulators of endometrial stromal cell differentiation, known as decidualization, which is a prerequisite for successful establishment of pregnancy. The present study using primary human endometrial stromal cells (HESCs) addressed the role of estrogen receptor-alpha (ESR1) in decidualization. Knockdown of ESR1 transcripts by RNA interference led to a marked reduction in decidualization of HESCs. Gene expression profiling at an early stage of decidualization indicated that ESR1 negatively regulates several cell cycle regulatory factors, thereby suppressing the proliferation of HESCs as these cells enter the differentiation program. ESR1 also controls the expression of WNT4, FOXO1, and progesterone receptor (PGR), well-known mediators of decidualization. Whereas ESR1 knockdown strongly inhibited the expression of FOXO1 and WNT4 transcripts within 24 hours of the initiation of decidualization, PGR expression remained unaffected at this early time point. Our study also revealed a major role of cAMP signaling in influencing the function of ESR1 during decidualization. Using a proteomic approach, we discovered that the cAMP-dependent protein kinase A (PKA) phosphorylates Mediator 1 (MED1), a subunit of the mediator coactivator complex, during HESC differentiation. Using immunoprecipitation, we demonstrated that PKA phosphorylated MED1 interacts with ESR1. The PKA-dependent phosphorylation of MED1 was also correlated with its enhanced recruitment to estrogen-responsive elements in the WNT4 gene. Knockdown of MED1 transcripts impaired the expression of ESR1-induced WNT4 and FOXO1 transcripts and blocked decidualization. Based on these findings, we conclude that modulation of ESR1-MED1 interactions by cAMP signaling plays a critical role in human decidualization. PMID- 26849467 TI - GRK2 Up-Regulation Creates a Positive Feedback Loop for Catecholamine Production in Chromaffin Cells. AB - Elevated sympathetic nervous system (SNS) activity aggravates several diseases, including heart failure. The molecular cause(s) underlying this SNS hyperactivity are not known. We have previously uncovered a neurohormonal mechanism, operating in adrenomedullary chromaffin cells, by which circulating catecholamine (CA) levels increase in heart failure: severe dysfunction of the adrenal alpha2 adrenergic receptors (ARs) due to the up-regulation of G protein-coupled receptor kinase (GRK)-2, the kinase that desensitizes them. Herein we looked at the potential signaling mechanisms that bring about this GRK2 elevation in chromaffin cells. We found that chronic CA treatment of either PC12 or rat primary chromaffin cells can in itself result in GRK2 transcriptional up-regulation through alpha2ARs-Gi/o proteins-Src-ERK1/2. The resultant GRK2 increase severely enhances the alpha2AR desensitization/down-regulation elevating not only CA release but also CA biosynthesis, as evidenced by tyrosine hydroxylase up regulation. Finally, GRK2 knockdown leads to enhanced apoptosis of PC12 cells, indicating an essential role for GRK2 in chromaffin cell homeostasis/survival. In conclusion, chromaffin cell GRK2 mediates a positive feedback loop that feeds into CA secretion, thereby enabling the adrenomedullary component of the SNS to turn itself on. PMID- 26849470 TI - Erratum to "A New Algorithm for Time-Delay Estimation in Ultrasonic Echo Signals". PMID- 26849469 TI - The Barriers and Facilitators to Transfer of Ultrasound-Guided Central Venous Line Skills From Simulation to Practice: Exploring Perceptions of Learners and Supervisors. AB - PHENOMENON: Ultrasound-guided central venous line insertion is currently the standard of care. Randomized controlled trials and systematic reviews show that simulation is superior to apprenticeship training. The purpose of this study is to explore, from the perspectives of participants in a simulation-training program, the factors that help or hinder the transfer of skills from simulation to practice. APPROACH: Purposeful sampling was used to select and study the experience and perspective of novice fellows after they had completed simulation training and then performed ultrasound-guided central venous line in practice. Seven novice pediatric intensive care unit fellows and six supervising faculty in a university-affiliated academic center in a large urban city were recruited between September 2012 and January 2013. We conducted a qualitative study using semistructured interviews as our data source, employing a constructivist, grounded theory methodology. FINDINGS: Both curricular and real-life factors influence the transfer of skills from simulation to practice and the overall performance of trainees. Clear instructions, the opportunity to practice to mastery, one-on-one observation with feedback, supervision, and further real-life experiences were perceived as factors that facilitated the transfer of skills. Concern for patient welfare, live trouble shooting, complexity of the intensive care unit environment, and the procedure itself were perceived as real-life factors that hindered the transfer of skills. Insights: As more studies confirm the superiority of simulation training versus apprenticeship training for initial student learning, the faculty should gain insight into factors that facilitate and hinder the transfer of skills from simulation to bedside settings and impact learners' performances. As simulation further augments clinical learning, efforts should be made to modify the curricular and bedside factors that facilitate transfer of skills from simulation to practice settings. PMID- 26849468 TI - Protein profile of basal prostate epithelial progenitor cells--stage-specific embryonal antigen 4 expressing cells have enhanced regenerative potential in vivo. AB - The long-term propagation of basal prostate progenitor cells ex vivo has been very difficult in the past. The development of novel methods to expand prostate progenitor cells in vitro allows determining their cell surface phenotype in greater detail. Mouse (Lin(-)Sca-1(+) CD49f(+) Trop2(high)-phenotype) and human (Lin(-) CD49f(+) TROP2(high)) basal prostate progenitor cells were expanded in vitro. Human and mouse cells were screened using 242 anti-human or 176 antimouse monoclonal antibodies recognizing the cell surface protein profile. Quantitative expression was evaluated at the single-cell level using flow cytometry. Differentially expressed cell surface proteins were evaluated in conjunction with the known CD49f(+)/TROP2(high) phenotype of basal prostate progenitor cells and characterized by in vivo sandwich-transplantation experiments using nude mice. The phenotype of basal prostate progenitor cells was determined as CD9(+)/CD24(+)/CD29(+)/CD44(+)/CD47(+)/CD49f(+)/CD104(+)/CD147(+)/CD326(+)/Trop2( igh) of mouse as well as human origin. Our analysis revealed several proteins, such as CD13, Syndecan-1 and stage-specific embryonal antigens (SSEAs), as being differentially expressed on murine and human CD49f(+) TROP2(+) basal prostate progenitor cells. Transplantation experiments suggest that CD49f(+) TROP2(high) SSEA-4(high) human prostate basal progenitor cells to be more potent to regenerate prostate tubules in vivo as compared with CD49f(+) TROP2(high) or CD49f(+) TROP2(high) SSEA-4(low) cells. Determination of the cell surface protein profile of functionally defined murine and human basal prostate progenitor cells reveals differentially expressed proteins that may change the potency and regenerative function of epithelial progenitor cells within the prostate. SSEA-4 is a candidate cell surface marker that putatively enables a more accurate identification of the basal PESC lineage. PMID- 26849471 TI - Effects of selenium supplementation on the oxidative state of acute heat stress exposed quails. AB - This study aimed to evaluate the effect of heat stress (HS) and selenium supplementation on markers of stress, meat quality and gene expression. For this, meat quails of 42 days of age were fed a diet that either met [0.33 mg/kg, nutritional demand for selenium (SS)] or did not meet [0.11 mg/kg, selenium deficient (SD)] the nutritional demands for selenium during the 7 days of evaluation. In addition, the animals were kept at either a thermal comfort temperature (25 degrees C) or exposed to HS (38 degrees C for 24 h). Glutathione synthetase (GSS), glutathione reductase (GSR) and uncoupling protein (UCP) gene expression were influenced by the interaction between temperature and diet. Animals subjected to HS and fed the SS diet exhibited the highest GSS and GSR gene expression. In terms of UCP gene expression, the lowest values were observed in HS animals on the SD diet. Glutathione peroxidase 7 (GPX7) gene expression, body temperature (BT) and creatine kinase (CK) activity were influenced by both selenium supplementation and HS. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) activity and creatinine content all were influenced by the diet/environment interaction. The highest AST activity, ALT activity and creatinine levels were observed in animals that were both on the SD diet and exposed to HS. HS animals also exhibited an increased heterophil/lymphocyte ratio and lower triiodothyronine (T3) hormone levels than birds that remained at the comfortable temperature. Animals subjected to HS and fed with selenium supplemented diet showed better results regarding gene expression and, thus, better results for the activities of enzymes used as stress markers, which could be due to the higher antioxidant capacity provided by the action of the studied genes. PMID- 26849472 TI - Misoprostol for Prevention of Postpartum Hemorrhage at Home Birth in Afghanistan: Program Expansion Experience. AB - INTRODUCTION: Afghanistan has a maternal mortality ratio of 400 per 100,000 live births. Hemorrhage is the leading cause of maternal death. Two-thirds of births occur at home. A pilot program conducted from 2005 to 2007 demonstrated the effectiveness of using community health workers for advance distribution of misoprostol to pregnant women for self-administration immediately following birth to prevent postpartum hemorrhage. The Ministry of Public Health requested an expansion of the pilot to study implementation on a larger scale before adopting the intervention as national policy. The purpose of this before-and-after study was to determine the effectiveness of advance distribution of misoprostol for self-administration across 20 districts in Afghanistan and identify any adverse events that occurred during expansion. METHODS: Cross-sectional household surveys were conducted pre- (n = 408) and postintervention (n = 408) to assess the effect of the program on uterotonic use among women who had recently given birth. Maternal death audits and verbal autopsies were conducted to investigate peripartum maternal deaths that occurred during implementation in the 20 districts. RESULTS: Uterotonic use among women in the sample increased from 50.3% preintervention to 74.3% postintervention. Because of a large-scale investment in Afghanistan in training and deployment of community midwives, it was assumed that all women who gave birth in facilities received a uterotonic. A significant difference in uterotonic use at home births was observed among women who lived farthest from a health facility (> 90 minutes self-reported travel time) compared to women who lived closer (88.5% vs 38.9%; P < .0001). All women who accepted misoprostol and gave birth at home used the drug. No maternal deaths were identified among those women who used misoprostol. DISCUSSION: The results of this study build on the findings of the pilot program and provide evidence on the effectiveness, primarily measured by uterotonic use, of an expansion of advance distribution of misoprostol for self-administration. PMID- 26849473 TI - Monitoring Tyrosinase Expression in Non-metastatic and Metastatic Melanoma Tissues by Scanning Electrochemical Microscopy. AB - Although tremendous progress has been made in the diagnosis of melanoma, the identification of different stages of malignancy in a reliable way remains challenging. Current strategies rely on optical monitoring of the concentration and spatial distribution of specific biomarkers. State-of-the-art optical methods can be affected by background-color interference and autofluorescence. We overcame these shortcomings by employing scanning electrochemical microscopy (SECM) to map the prognostic indicator tyrosinase (TyR) in non-metastatic and metastatic melanoma tissues by using soft-stylus microelectrodes. Electrochemical readout of the TyR distribution was enabled by adapting an immunochemical method. SECM can overcome the limitations of optical methods and opens unprecedented possibilities for improved diagnosis and understanding of the spatial distribution of TyR in different melanoma stages. PMID- 26849474 TI - Synthesis and in Vitro Studies of a Series of Carborane-Containing Boron Dipyrromethenes (BODIPYs). AB - A series of seven BODIPYs functionalized with ortho-carborane groups at the 8(meso) or 3/5(alpha) position were synthesized and characterized by NMR, HRMS, HPLC, and in the cases of 2b and 5b, by X-ray analysis. The BODIPYs exhibited low dark toxicity and phototoxicity toward human glioma T98G cells, and their cellular uptake varied significantly, with 5b accumulating the most and 7 the least. All BODIPYs localized mainly within the cell ER. The BODIPYs showed higher permeabilities than lucifer yellow across human hCMEC/D3 brain endothelial cell monolayers as the BBB model. Among this series, 1b showed the highest BBB permeability (Pe = 16.4 * 10(-5) cm/s), probably as a result of its lower MW (366 Da) and favorable hydrophobicity (log P = 1.5). The combination of low cytotoxicity, amphiphilicity, high boron content, high cellular uptake, and moderate BBB permeability renders these compounds promising boron delivery agents for the BNCT of brain tumors. PMID- 26849475 TI - Indigenous birth outcomes at a Victorian urban hospital, a retrospective 5-year cohort study 2010-2014. AB - BACKGROUND: Indigenous people in Australia experience higher rates of preterm birth and low birthweight than their nonindigenous counterparts. There is currently no data on these rates from Victoria, with the data coming from states with higher indigenous proportions. MATERIALS AND METHODS: Five years (1st January 2010-31st December 2014) of retrospective data from The Northern Hospital's (Melbourne, Victoria) database were analysed. Mothers and babies were split according to self-reported indigenous status: 13800 nonindigenous mothers, 185 indigenous mothers, 301 indigenous babies and 13843 nonindigenous babies. Primary outcomes measured were low birthweight (LBW) and preterm birth. RESULTS: There was a higher incidence of indigenous babies born preterm (8.8% vs 5.9%, P = 0.034), but the adjusted odds ratios for preterm birth were not significant (indigenous babies OR 1.19, 95% CI: 0.77-1.87, indigenous mothers OR 0.97, CI: 0.52-1.80). There was a similar incidence of LBW among indigenous and nonindigenous babies (6.5% vs 5.4%, P = 0.416). The rate of indigenous women smoking was 29.3% compared to 12.3% of nonindigenous women (P < 0.001), and 40.3% were obese compared to 28.7% (P = 0.001). Indigenous women had lower rates of diabetes (pre-existing or gestational diabetes, 6.1% vs 13.5% P = 0.003). CONCLUSION: Heterogeneity of indigenous people and geography means that inferences about indigenous health are difficult to make. It appears that Victorian urban indigenous women have similar rates of preterm birth and LBW to nonindigenous women. While there were pleasing results concerning LBW, antenatal care, diabetes and preterm birth, the rates of smoking and obesity remain a challenge in the indigenous population. PMID- 26849477 TI - Effects on muscle strength, maximal jump height, flexibility and postural sway after soccer and Zumba exercise among female hospital employees: a 9-month randomised controlled trial. AB - This 9-month randomised controlled workplace physical activity trial investigated the effects of soccer and Zumba exercise, respectively, on muscle strength, maximal jump height, sit-and-reach flexibility and postural sway among female workers. A total of 107 female hospital employees aged 25-63 were cluster randomised to a soccer group, a Zumba group or a control group. Training was conducted outside working hours as two to three 1-h weekly sessions the first 3 months and once a week the last 6 months. Tests were conducted at baseline, after 3 and 9 months. The soccer group improved maximal neck extension strength both after 3 (1.2 kg; P < 0.05) and 9 months (1.7 kg; P < 0.01) compared to the control group. The Zumba group improved maximal trunk extension strength (3.1 kg; P = 0.04) after 3 months, with improvements in postural sway velocity moment ( 9.2 mm(2)/s; P < 0.05) and lower limb lean mass (0.4 kg; P < 0.05) after 9 months. No significant intervention effects were revealed in vertical jump height or sit-and-reach flexibility. The present study indicates that workplace initiated soccer and Zumba exercise may be beneficial for improvement of the neck and trunk strength, which may have preventive effects with regard to future perceived muscle pain in the respective body regions. Furthermore, the Zumba group revealed positive effects on lower limb lean mass and postural sway compared to the control group. PMID- 26849476 TI - The expanding role of neuropilin: regulation of transforming growth factor-beta and platelet-derived growth factor signaling in the vasculature. AB - PURPOSE OF REVIEW: Long recognized for its role in regulation of vascular endothelial growth factor signaling, neuropilin (Nrp)1 has emerged as a modulator of additional signaling pathways critical for vascular development and function. Here we review two novel functions of Nrp1 in blood vessels: regulation of transforming growth factor-beta (TGFbeta) signaling in endothelial cells and regulation of platelet-derived growth factor (PDGF) signaling in vascular smooth muscle cells. RECENT FINDINGS: Novel mouse models demonstrate that Nrp1 fulfills vascular functions independent of vascular endothelial growth factor signaling. These include modulation of TGFbeta-dependent inhibition of endothelial sprouting during developmental angiogenesis and PDGF signaling in vascular smooth muscle cells during development and disease. SUMMARY: Broadening our understanding of how and where Nrp1 functions in the vasculature is critical for the development of targeted therapeutics for cancer and vascular diseases such as atherosclerosis and retinopathies. PMID- 26849478 TI - DEPDC5 mutations in epilepsy with auditory features. PMID- 26849479 TI - In response: DEPDC5 mutations in epilepsy with auditory features. PMID- 26849481 TI - Clarification Statement. PMID- 26849482 TI - The Key Role of Experiential Uncertainty when Dealing with Risks: Its Relationships with Demand for Regulation and Institutional Trust. AB - The results of a survey and an experiment show that experiential uncertainty people's experience of uncertainty in risk contexts-plays a moderating role in individuals' risk-related demand for government regulation and trust in risk managing government institutions. First, descriptions of risks were presented to respondents in a survey (N = 1,017) and their reactions to questions about experiential uncertainty, risk perception, and demand for government regulation were measured, as well as levels of risk-specific knowledge. When experiential uncertainty was high, risk perceptions had a positive relationship with demand for government regulation of risk; no such relationship showed under low experiential uncertainty. Conversely, when people experience little experiential uncertainty, having more knowledge about the risk topic involved was associated with a weaker demand for government regulation of risk. For people experiencing uncertainty, this relationship between knowledge and demand for regulation did not emerge. Second, in an experiment (N = 120), experiential uncertainty and openness in risk communication were manipulated to investigate effects on trust. In the uncertainty condition, the results showed that open versus nonopen government communication about Q-fever-a zoonosis-led to higher levels of trust in the government agency, but not in in the control condition. Altogether, this research suggests that only when people experience relatively little uncertainty about the risk, knowledge provision may preclude them from demanding government action. Also, only when persons experience uncertainty are stronger risk perceptions associated with a demand for government regulation, and they are affected by openness of risk communication in forming institutional trust. PMID- 26849483 TI - Perceptions of diabetes control among physicians and people with type 2 diabetes uncontrolled on basal insulin in Sweden, Switzerland, and the United Kingdom. AB - Objective A large proportion of people with type 2 diabetes (T2D) remain uncontrolled on basal insulin. Yet, there is limited understanding of how people with uncontrolled type 2 diabetes (PWUD) perceive control and insulin intensification and whether their perceptions differ from those of physicians. The purpose of the study was to investigate perceptions of control and views on insulin intensification among physicians and PWUD. Research design and methods Web surveys of 1012 PWUD on basal insulin and 300 physicians were conducted in Sweden, Switzerland, and the United Kingdom. Results Analyses revealed significant differences between physicians and PWUD. Physicians were significantly more likely than PWUD to indicate that HbA1c (85.0% vs. 78.9%, p < 0.05), complications from diabetes (89.3% vs. 75.3%, p < 0.001), and frequency/severity of hypoglycemia (93.3% vs. 68.6%, p < 0.001) were very/extremely important for deciding whether or not diabetes is well controlled. In contrast PWUD were significantly more likely to place importance on a variety of factors, including energy levels (74.5% vs. 33.0%, p < 0.001), insulin units/day (77.6% vs. 29.0%, p < 0.001) and how predictable life is (72.1% vs. 29.3%, p < 0.001). PWUD also perceived significantly greater obstacles to control and viewed uncontrolled T2D as more interfering in their lives compared to physicians. Physicians were most reluctant to intensify insulin when there is a lack of patient agreement. Worries about weight gain and feelings of 'getting sicker' were the most frequently reported reasons why PWUD on basal insulin were reluctant to intensify insulin. Conclusions Results revealed a significant disconnect between physicians and PWUD in their perceptions of diabetes control. While physicians generally expressed a more focused and clinical view of diabetes control, patients had a broader view. Results also provide insights into PWUD and physicians' reluctance to intensify insulin. The findings suggest that physician and patient education on differing perceptions could benefit communication and improve diabetes management. PMID- 26849485 TI - Linda Peters 1964-2015. PMID- 26849484 TI - Dendritic spine actin dynamics in neuronal maturation and synaptic plasticity. AB - The majority of the postsynaptic terminals of excitatory synapses in the central nervous system exist on small bulbous structures on dendrites known as dendritic spines. The actin cytoskeleton is a structural element underlying the proper development and morphology of dendritic spines. Synaptic activity patterns rapidly change actin dynamics, leading to morphological changes in dendritic spines. In this mini-review, we will discuss recent findings on neuronal maturation and synaptic plasticity-induced changes in the dendritic spine actin cytoskeleton. We propose that actin dynamics in dendritic spines decrease through actin filament crosslinking during neuronal maturation. In long-term potentiation, we evaluate the model of fast breakdown of actin filaments through severing and rebuilding through polymerization and later stabilization through crosslinking. We will discuss the role of Ca(2+) in long-term depression, and suggest that actin filaments are dissolved through actin filament severing. (c) 2016 Wiley Periodicals, Inc. PMID- 26849486 TI - Research that matters--clinical studies. PMID- 26849487 TI - Cone beam computed tomography in Endodontics. PMID- 26849488 TI - Response to the letter entitled: 'Cone beam computed tomography in Endodontics'. PMID- 26849489 TI - Wedding Imagery and Public Support for Gay Marriage. AB - This study uses an experiment embedded in a large, nationally representative survey to test whether exposure to imagery of a gay or lesbian couple's wedding influences support for gay marriage. It also tests whether any such effects depend on the nature of the image (gay or lesbian couple, kissing or not) and viewer characteristics (sex, age, race, education, religion, and ideology). Results show that exposure to imagery of a gay couple kissing reduced support for gay marriage relative to the baseline. Other image treatments (gay couple not kissing, lesbian couple kissing, lesbian couple not kissing) did not significantly influence opinion. PMID- 26849490 TI - Association between catechol-O-methyl transferase gene polymorphisms and fibromyalgia in a Korean population: A case-control study. AB - BACKGROUND: Although polymorphisms of the catechol-O-methyl transferase (COMT) gene have been implicated in altered pain sensitivity, results concerning the association between COMT gene polymorphisms and fibromyalgia (FM) are equivocal. We assessed the associations between COMT single-nucleotide polymorphisms (SNP) and FM risk and symptom severity. METHODS: In total, 409 FM patients and 423 controls were enrolled. Alleles and genotypes at five positions [rs6269 (A>G), rs4633 (C>T), rs4818 (C>G), rs4680 (C>G) and rs165599 (A>G)] in the COMT gene were genotyped from peripheral blood DNA. RESULTS: Alleles and genotypes of the rs4818 COMT gene polymorphism were significantly associated with increased susceptibility to FM. The rs4818 GG genotype was more strongly associated with FM compared to the CC genotype (OR = 1.680, 95% CI: 1.057, 2.672, p = 0.027). Although allele and genotype frequencies did not differ among groups, the rs4633 CT genotype was not associated with the presence of FM following adjustment for age and sex (OR = 0.745; 95% CI: 0.558, 0.995; p = 0.046). However, no association was observed between clinical measures and individual COMT SNPs. In haplotype analysis, there was a significant association between ACG haplotype and FM susceptibility sex (OR = 2.960, 95% CI: 1.447, 6.056, p = 0.003) and the number of tender points (p = 0.046). CONCLUSIONS: This large-scale study suggests that polymorphisms of the COMT gene may be associated with FM risk and pain sensitivity in Korean FM patients. However, our results differed to those of previous studies, suggesting ethnic variation in COMT gene polymorphisms in FM. WHAT DOES THIS STUDY ADD: By contrast to Caucasian and Latin-American populations, the COMT gene polymorphisms are associated with FM risk and pain sensitivity in Korean FM patients, suggesting ethnic variation in COMT gene polymorphisms. PMID- 26849492 TI - Gold-Quantum Dot Core-Satellite Assemblies for Lighting Up MicroRNA In Vitro and In Vivo. AB - A high yield DNA-driven gold-quantum dot core-satellite is developed for miRNA detection in vitro and vivo. In the presence of the target miRNA, the DNA hairpin between core and satellite is ruined, resulting in the recovery of fluorescence. The limit of detection for miRNA-21 detection in living cells reaches 296 copies per cell. PMID- 26849494 TI - Don't put all your eggs in one basket: a cost-effective and powerful method to optimize primer choice for rRNA environmental community analyses using the Fluidigm Access Array. AB - With the increasing democratization of high-throughput sequencing (HTS) technologies, along with the concomitant increase in sequence yield per dollar, many researchers are exploring HTS for microbial community ecology. Many elements of experimental design can drastically affect the final observed community structure, notably the choice of primers for amplification prior to sequencing. Some targeted microbes can fail to amplify due to primer-targeted sequence divergence and be omitted from obtained sequences, leading to differences among primer pairs in the sequenced organisms even when targeting the same community. This potential source of taxonomic bias in HTS makes it prudent to investigate how primer choice will affect the sequenced community prior to investing in a costly community-wide sequencing effort. Here, we use Fluidigm's microfluidic Access Arrays (IFC) followed by Illumina((r)) MiSeq Nano sequencing on a culture derived local mock community to demonstrate how this approach allows for a low cost combinatorial investigation of primer pairs and experimental samples (up to 48 primer pairs and 48 samples) to determine the most effective primers that maximize obtained communities whilst minimizing taxonomic biases. PMID- 26849493 TI - Dynamic DNA methylation controls glutamate receptor trafficking and synaptic scaling. AB - Hebbian plasticity, including long-term potentiation and long-term depression, has long been regarded as important for local circuit refinement in the context of memory formation and stabilization. However, circuit development and stabilization additionally relies on non-Hebbian, homeostatic, forms of plasticity such as synaptic scaling. Synaptic scaling is induced by chronic increases or decreases in neuronal activity. Synaptic scaling is associated with cell-wide adjustments in postsynaptic receptor density, and can occur in a multiplicative manner resulting in preservation of relative synaptic strengths across the entire neuron's population of synapses. Both active DNA methylation and demethylation have been validated as crucial regulators of gene transcription during learning, and synaptic scaling is known to be transcriptionally dependent. However, it has been unclear whether homeostatic forms of plasticity such as synaptic scaling are regulated via epigenetic mechanisms. This review describes exciting recent work that has demonstrated a role for active changes in neuronal DNA methylation and demethylation as a controller of synaptic scaling and glutamate receptor trafficking. These findings bring together three major categories of memory-associated mechanisms that were previously largely considered separately: DNA methylation, homeostatic plasticity, and glutamate receptor trafficking. This review describes exciting recent work that has demonstrated a role for active changes in neuronal DNA methylation and demethylation as a controller of synaptic scaling and glutamate receptor trafficking. These findings bring together three major categories of memory associated mechanisms that were previously considered separately: glutamate receptor trafficking, DNA methylation, and homeostatic plasticity. PMID- 26849496 TI - Research not fit to print. PMID- 26849495 TI - gH/gL supercomplexes at early stages of herpesvirus entry. AB - Membrane fusion during herpesvirus entry into host cells is a complex process where multiple glycoproteins interact to relay the triggering signal from a receptor-binding protein to the conserved fusogen gB through the conserved heterodimer gH/gL. Crystal structures of individual glycoproteins are available, yet high-order 'supercomplexes' have been elusive. Recent structures of complexes between gH/gL from human cytomegalovirus or Epstein-Barr virus and the receptor binding proteins that form at early stages of herpesviral entry highlighted mechanisms that control tropism and revealed dynamic intermediate complexes containing gH/gL that may directly participate in membrane deformation and juxtaposition. Determining how the triggering signal reaches the fusogen gB represents the next frontier in structural biology of herpesvirus entry. PMID- 26849497 TI - FDA approves 'farmaceutical' drug from transgenic chickens. PMID- 26849498 TI - Obama's cancer moonshot. PMID- 26849499 TI - Biotechs target stagnant baldness market. PMID- 26849500 TI - CRISPR patents to go on trial. PMID- 26849501 TI - Bayer joins CRISPR. PMID- 26849502 TI - Proteasome play C4 debuts. PMID- 26849503 TI - Direct Genomics revives Helicos sequencing system for China's hospitals. PMID- 26849504 TI - New partner for Galapagos JAK drug. PMID- 26849505 TI - Chimera research under the spotlight. PMID- 26849506 TI - Around the world in a month. PMID- 26849507 TI - Corrections. PMID- 26849508 TI - FDA approves three different multiple myeloma drugs in one month. PMID- 26849509 TI - 2015--another banner year for biotech. PMID- 26849510 TI - Drug pipeline Q4 2015. PMID- 26849511 TI - Fresh from the biotech pipeline--2015. PMID- 26849512 TI - Preparing for crises. PMID- 26849513 TI - Cas9-triggered chain ablation of cas9 as a gene drive brake. PMID- 26849514 TI - Precision and robustness of 2D-NMR for structure assessment of filgrastim biosimilars. PMID- 26849515 TI - Evolving Japanese regulations on companion diagnostics. PMID- 26849516 TI - Persistent confusion and controversy surrounding gene patents. PMID- 26849518 TI - Can CRISPR-Cas9 gene drives curb malaria? PMID- 26849519 TI - Mapping regulatory elements. PMID- 26849520 TI - Personalized nutrition through big data. PMID- 26849522 TI - Erratum: Share and share alike. PMID- 26849523 TI - Corrigendum: Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining. PMID- 26849524 TI - Erratum: Analysis of intronic and exonic reads in RNA-seq data characterizes transcriptional and post-transcriptional regulation. PMID- 26849525 TI - Fourth-quarter biotech job picture. PMID- 26849528 TI - Metallic nickel nanoparticles and their effect on the embryonic development of the sea urchin Paracentrotus lividus. AB - The presence of nanoparticles in many industrial applications and daily products is making it nowadays crucial to assess their impact when exposed to the environment. Metallic nickel nanoparticles (Ni NPs) are of high industrial interest due to their ability to catalyze the reversible hydration of CO2 to carbonic acid at ambient conditions. We characterized metallic Ni NPs by XRD, HRTEM and EDS and determined the solubility of free nickel ions from 3 mg/L metallic Ni NPs in seawater by ICP-MS over 96 h, which was below 3%. Further, embryonic development of the sea urchin Paracentrotus lividus was investigated for 48 h in the presence of metallic Ni NPs (0.03 mg/L to 3 mg/L), but no lethal effects were observed. However, 3 mg/L metallic Ni NPs caused a size reduction similar to 1.2 mg/L NiCl2*6 H2O. The obtained results contribute to current studies on metallic Ni NPs and point to their consequences for the marine ecosystem. PMID- 26849527 TI - Clostridium difficile associated risk of death score (CARDS): a novel severity score to predict mortality among hospitalised patients with C. difficile infection. AB - BACKGROUND: Clostridium difficile infection (CDI) is a public health threat and associated with significant mortality. However, there is a paucity of objectively derived CDI severity scoring systems to predict mortality. AIM: To develop a novel CDI risk score to predict mortality entitled: Clostridium difficile associated risk of death score (CARDS). METHODS: We obtained data from the United States 2011 Nationwide Inpatient Sample (NIS) database. All CDI-associated hospitalisations were identified using discharge codes (ICD-9-CM, 008.45). Multivariate logistic regression was utilised to identify independent predictors of mortality. Clostridium difficile associated risk of death score was calculated by assigning a numeric weight to each parameter based on their odds ratio in the final logistic model. Predictive properties of model discrimination were assessed using the c-statistic and validated in an independent sample using the 2010 NIS database. RESULTS: We identified 77 776 hospitalisations, yielding an estimate of 374 747 cases with an associated diagnosis of CDI in the US, 8% of whom died in the hospital. The eight severity score predictors were identified on multivariate analysis: age, cardiopulmonary disease, malignancy, diabetes, inflammatory bowel disease, acute renal failure, liver disease and ICU admission, with weights ranging from -1 (for diabetes) to 5 (for ICU admission). The overall risk score in the cohort ranged from 0 to 18. Mortality increased significantly as CARDS increased. CDI-associated mortality was 1.2% with a CARDS of 0 compared to 100% with CARDS of 18. The model performed equally well in our validation cohort. CONCLUSION: Clostridium difficile associated risk of death score is a promising simple severity score to predict mortality among those hospitalised with C. difficile infection. PMID- 26849529 TI - Aerobic biotransformation of polyfluoroalkyl phosphate esters (PAPs) in soil. AB - Microbial transformation of polyfluoroalkyl phosphate esters (PAPs) into perfluorocarboxylic acids (PFCAs) has recently been confirmed to occur in activated sludge and soil. However, there lacks quantitative information about the half-lives of the PAPs and their significance as the precursors to PFCAs. In the present study, the biotransformation of 6:2 and 8:2 diPAP in aerobic soil was investigated in semi-dynamics reactors using improved sample preparation methods. To develop an efficient extraction method for PAPs, six different extraction solvents were compared, and the phenomenon of solvent-enhanced hydrolysis was investigated. It was found that adding acetic acid could enhance the recoveries of the diPAPs and inhibit undesirable hydrolysis during solvent extraction of soil. However 6:2 and 8:2 monoPAPs, which are the first breakdown products from diPAPs, were found to be unstable in the six solvents tested and quickly hydrolyzed to form fluorotelomer alcohols. Therefore reliable measurement of the monoPAPs from a live soil was not achievable. The apparent DT50 values of 6:2 diPAP and 8:2 diPAP biotransformation were estimated to be 12 and > 1000 days, respectively, using a double first-order in parallel model. At the end of incubation of day 112, the major degradation products of 6:2 diPAP were 5:3 fluorotelomer carboxylic acid (5:3 acid, 9.3% by mole), perfluoropentanoic acid (PFPeA, 6.4%) and perfluorohexanoic acid (PFHxA, 6.0%). The primary product of 8:2 diPAP was perfluorooctanoic acid (PFOA, 2.1%). The approximately linear relationship between the half-lives of eleven polyfluoroalkyl and perfluoroalkyl substances (PFASs, including 6:2 and 8:2 diPAPs) that biotransform in aerobic soils and their molecular weights suggested that the molecular weight is a good indicator of the general stability of low-molecular-weight PFAS-based compounds in aerobic soils. PMID- 26849530 TI - Resting-State Peripheral Catecholamine and Anxiety Levels in Korean Male Adolescents with Internet Game Addiction. AB - The purpose of this study was to compare the resting-state plasma catecholamine and anxiety levels of Korean male adolescents with Internet game addiction (IGA) and those without IGA. This cross-sectional comparative study was conducted with 230 male high school students in a South Korean city. Convenience and snowball sampling methods were employed, and data were collected using (1) participant blood samples analyzed for dopamine (DA), epinephrine (Epi), and norepinephrine (NE) and (2) two questionnaires to assess IGA and anxiety levels. Using SPSS 15.0, data were analyzed by descriptive analysis, chi(2)-tests, t-tests, and Pearson's correlation tests. The plasma Epi (t = 1.962, p < 0.050) and NE (t = 2.003, p = 0.046) levels were significantly lower in the IGA group than in the non-IGA group; DA levels did not significantly differ between the groups. The mean anxiety level of the IGA group was significantly higher compared with the non-IGA group (t = -6.193, p < 0.001). No significant correlations were found between catecholamine and anxiety levels. These results showed that excessive Internet gaming over time induced decreased peripheral Epi and NE levels, thus altering autonomic regulation, and increasing anxiety levels in male high school students. Based on these physiological and psychological effects, interventions intended to prevent and treat IGA should include stabilizing Epi, NE, and anxiety levels in adolescents. PMID- 26849532 TI - New Series of Polar and Nonpolar Platinum Iodates A2Pt(IO3)6 (A = H3O, Na, K, Rb, Cs). AB - A new series of platinum iodates, namely, alpha-(H3O)2Pt(IO3)6, beta (H3O)2Pt(IO3)6, and A2Pt(IO3)6 (A = Na, K, Rb, Cs), have been synthesized. Interestingly, among these six stoichiometrically identical compounds, alpha (H3O)2Pt(IO3)6 is polar, whereas other compounds are nonpolar and centrosymmetric. They all consist of zero-dimensional [Pt(IO3)6](2-) molecular units separated by H3O(+) or A(+) cations. All of the lone electron pairs of the IO3(-) groups are aligned and almost point to one direction for alpha (H3O)2Pt(IO3)6, whereas IO3(-) groups are located trans to each other in other compounds. The material, alpha-(H3O)2Pt(IO3)6, exhibits very strong second harmonic generation (SHG) effects, approximately 1.2 * KTiOPO4 (KTP), and is phase-matchable. Thermogravimetric analysis, elemental analysis, infrared spectra, UV-vis spectra, nonlinear optical properties, and theoretical calculations are also reported. PMID- 26849531 TI - Quantum Yield Heterogeneity among Single Nonblinking Quantum Dots Revealed by Atomic Structure-Quantum Optics Correlation. AB - Physical variations in colloidal nanostructures give rise to heterogeneity in expressed optical behavior. This correlation between nanoscale structure and function demands interrogation of both atomic structure and photophysics at the level of single nanostructures to be fully understood. Herein, by conducting detailed analyses of fine atomic structure, chemical composition, and time resolved single-photon photoluminescence data for the same individual nanocrystals, we reveal inhomogeneity in the quantum yields of single nonblinking "giant" CdSe/CdS core/shell quantum dots (g-QDs). We find that each g-QD possesses distinctive single exciton and biexciton quantum yields that result mainly from variations in the degree of charging, rather than from volume or structure inhomogeneity. We further establish that there is a very limited nonemissive "dark" fraction (<2%) among the studied g-QDs and present direct evidence that the g-QD core must lack inorganic passivation for the g-QD to be "dark". Therefore, in contrast to conventional QDs, ensemble photoluminescence quantum yield is principally defined by charging processes rather than the existence of dark g-QDs. PMID- 26849533 TI - Microbial pathogenesis meets biomechanics. AB - Introducing concepts from soft matter physics and mechanics has largely contributed to our understanding of a variety of biological processes. In this review, we argue that this holds true for bacterial pathogenesis. We base this argument on three examples of bacterial pathogens and their interaction with host cells during infection: (i) Shigella flexneri exploits actin-dependent forces to come into close contact with epithelial cells prior to invasion of the epithelium; (ii) Neisseria meningitidis manipulates endothelial cells to resist shear stress during vascular colonization; (iii) bacterial toxins take advantage of the biophysical properties of the host cell plasma membrane to generate transcellular macroapertures in the vascular wall. Together, these examples show that a multidisciplinary approach integrating physics and biology is more necessary than ever to understand complex infectious phenomena. Moreover, this avenue of research will allow the exploration of general processes in cell biology, highlighted by pathogens, in the context of other non-communicable human diseases. PMID- 26849534 TI - Impact of the Fukushima nuclear accident on obesity of children in Japan (2008 2014). AB - This study used prefecture-level panel data from Japan for the period 2008-2014 to investigate the influence of the 2011 Fukushima nuclear accident on the body mass index (BMI) z-score and obesity rates of children over time. I adopted a difference-in-differences approach and found the following: (1) for the cohort aged 5-7 years in 2010, the BMI z-score and obesity rates in disaster-affected areas were higher than in other areas, although this was not observed for the other cohorts; (2) for the cohort aged 5-7 years in 2010, the influence of the accident persisted even after 3 years; and (3) the differences in the BMI z-score and obesity rate before and after the accident were greater for Fukushima Prefecture than for the other affected areas (Iwate and Miyagi prefectures). I infer that health-conscious parents, whose children had lower BMIs, may have moved from Fukushima, thereby increasing the BMI z-score of the child population living in Fukushima by around 0.05 for the cohort aged 5-7 years. The enforced reduction in physical activity increased the BMI z-score of children living in Fukushima by around 0.19 for that cohort. PMID- 26849535 TI - Human papillomavirus-associated oropharyngeal squamous cell carcinoma and anogenital cancers in men: Epidemiologic evaluation of association. AB - BACKGROUND: The purpose of this study was to investigate the possible epidemiological association between oropharyngeal carcinoma and anogenital tumors. METHODS: Population-based demographic and pathologic data on all male patients diagnosed with oropharyngeal squamous cell carcinoma (OPSCC) and anogenital cancer between 1980 and 2011 in the province of Alberta was collected. The risk of association between anogenital cancers and OPSCCs was estimated. RESULTS: Between 1980 and 2011, a total of 2105 male patients were diagnosed with OPSCC and 914 with anogenital cancers. Only 5 patients were diagnosed with both. CONCLUSION: In our male population, there was no significant association between anogenital and OPSCCs. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2100 E2102, 2016. PMID- 26849536 TI - Output Coupling of Perovskite Lasers from Embedded Nanoscale Plasmonic Waveguides. AB - Nanoscale lasers are ideal light-signal sources for integrated photonic devices. Most of the present lasers made of dielectric materials are restricted to being larger than half the wavelength of the optical field. Plasmon lasers made from metallic nanostructures can help to break the diffraction limit, yet they suffer from low optical pump efficiencies and low quality factors. Integrating dielectric lasers with plasmonic waveguides to construct hybrid material systems may circumvent these problems and combine the advantages of the two components. Here we demonstrate the nanoscale output of dielectric lasers via photon-plasmon coupling in rationally designed perovskite/silver heterostructures. The perovskite crystals offer the gain and high-Q cavity for low-threshold laser generation, while the embedded silver nanowires (AgNWs) help to output the lasing modes efficiently in the form of surface plasmons. The output coupling can be modulated by controlling the resonant modes of the two-dimensional perovskite microcavities. The results would pave an alternative avenue to ultrasmall light sources as well as fundamental studies of light-matter interactions. PMID- 26849537 TI - Effects of Exergames on Balance, Functional Mobility, and Quality of Life of Geriatrics Versus Home Exercise Programme: Randomized Controlled Study. AB - AIM: To compare the effects of exergames (EGs) using the Xbox KinectTM device and home exercise (HE) on balance, functional mobility, and quality of life of individuals aged 65 years or older. METHOD: One hundred participants who met the inclusion criteria were randomized to the EG or HE group. The EG group took part in a 6-week programme using the Xbox360KinectTM device, and the HE group took part in a 6-week balance exercise programme at home 5 days a week. The Berg Balance Scale (BBS) was used to assess balance, the Timed Up and Go (TUG) test was used to evaluate functional walking, and the Short Form 36 (SF-36) was used to assess quality of life. RESULTS: Forty-eight participants in the EG group and 42 participants in the HE group completed the study. The groups were similar in terms of age, sex, and pretreatment values of BBS, TUG, and SF-36. Although the BBS scores of both groups improved significantly (all p<0.05), the post-treatment scores of the EG group were better than those of the HE group. The TUG scores improved only in the EG group (p<0.05). The increase in the BBS scores and decrease in the TUG test scores were significant only in the EG group (all p<0.05). A significant improvement was also observed in the quality of life parameters of physical functioning, social role functioning, physical role restriction, general health perceptions, and physical component scores in the post-exercise evaluations of the EG group. The participants commented that they found the EG programme very entertaining. CONCLUSION: The EG can be considered a safe, entertaining and sustainable alternative to HE programmes, and it may have positive effects on balance, functional walking and quality of life in geriatric subjects. PMID- 26849538 TI - Body Composition Changes in Adult Females after Lifestyle Intervention Are Influenced by the NYD-SP18 Variant. AB - AIM: The study focuses on the analysis of the possible relationship between a common NYD-SP18 (rs6971091, G>A) gene polymorphism and weight loss after lifestyle intervention (combined dietary intake and physical activity) in overweight/obese females. METHODS: We genotyped 139 unrelated non-diabetic Czech females (49.5 +/- 13.3 years, average BMI at baseline 32.2 +/- 4.6 kg/m2. Biochemical and anthropometrical measurements were performed before and after ten weeks of lifestyle intervention. CONCLUSION: Overweight/obese female carriers of the NYD-SP18 rs6971091 GG genotype exhibited a more beneficial response to the intensive lifestyle intervention than others. PMID- 26849539 TI - Assessment of Environmental Determinants of Physical Activity: a Study of Built Environment Indicators in Brno, Czech Republic. AB - BACKGROUND: Research on physical activity in relation to obesity gradually becomes more focused on environmental determinants, which can potentially influence people's health choices. The present article addresses the topic of physical activity from a wider sociological perspective. Our pilot study was designed with the objective of testing the applicability of a method included in the EC 6th Framework Programme EURO-PREVOB, in the Czech context. The method examines specific determinants of the built environment that can have an impact on physical activity at the population level. In addition, the study aims to analyze possible differences in built environment indicators and their relation to the physical activity of people living in neighbourhoods with areas of varying socioeconomic status. METHODS: The field study was carried out in the city of Brno, Czech Republic, in 5 neighbourhood quintiles, i.e. areas divided according to the socioeconomic status of local residents. In each quintile, we evaluated the quality of the built environment according to the quality, aesthetics and safety of segregated cycle facilities, playgrounds/playing areas, public open spaces, marked road crossings and pavements as well as signs of incivilities and devastation. RESULTS: Between the five quintiles, significant differences were found in the quality of parks and playgrounds/playing areas, pavements, marking of pedestrian crossings, and in general aesthetics, i.e. signs of incivilities and devastation of the built environment. No differences were found in the quality and use of cycle facilities. CONCLUSIONS: The method we used for the evaluation of the built environment proved highly applicable in Czech populated areas. Monitoring of built environment indicators in the Czech Republic should provide a basis for health maps, showing potential associations between the prevalence of high-incidence, non-infectious diseases and various social determinants of physical activity. This information might help in achieving an improvement in these determinants at a community level and promoting an increase in physical activity at the population level. PMID- 26849540 TI - Physical Activity and Exercise as a Basic Preventive Measure (Primary Prevention, Prevention after Renal Transplantation). AB - Movement is an inseparable part of one's life, and has been a basic everyday activity through the history of mankind. However, a lack of physical activity and availability of food have resulted in a variety of serious health impairments. The 20th century has witnessed a steep rise of mortality from cardiovascular disease, increase in the prevalence of type-2 diabetes mellitus, malignant diseases, and dramatic increase in body weight initially in industrialized nations followed, in the last two decades of the last century, by the populations of third-world countries with all inherent consequences of this phenomenon. Preventive programmes involving physical activity have also been on the list of top priorities of various materials issued by the World Health Organization. Physical activity is one of the simplest non-pharmacological tools in the prevention of a plethora of diseases. The simplest physical activity, even for therapeutic purposes, is walking. We can walk any time, virtually anywhere, so walking is also the least expensive therapeutic option. PMID- 26849541 TI - Age and Gender Differences in Prevalence of Screen Based Behaviour, Physical Activity and Health Complaints among Slovak School-aged Children. AB - AIM: The aim of this study was to assess age and gender differences in prevalence of screen based behaviour, physical activity and health complaints among Slovak school-aged children. METHODS: Data from the cross-sectional Health Behaviour of School-aged Children study collected in 2010 among Slovak children (age 11-15 years, N=8,042) was used. Logistic regression models adjusted to age and gender were used to analyse the associations between watching TV, working with a computer or playing computer games and physical activity and headache, backache, sleep difficulties, feeling low, irritability, and feeling nervous. RESULTS: Around one-quarter of adolescents is spending more than three hours a day with screen-based activities. While the age was significantly associated with watching TV and computer use, gender was significantly associated only with excessive computer use. As for physical activity only 25% of adolescents reported being physically active every day as recommended, and this number decreases with increasing age. Boys used to be more often active in comparison with girls. A sizeable number of adolescents suffer with selected health complaints every week. Moreover, the prevalence of health complaints increases with age and is significantly higher among girls. CONCLUSIONS: The prevalence of screen-based activities as well as insufficient physical activity and health complaints among adolescents is relatively high and it increases with age. Gender differences are also significant, except for watching TV. PMID- 26849543 TI - Mental Load and Its Compensation by Physical Activity in Adolescents at Secondary Schools. AB - AIM: Sedentary behaviour and increasing mental load in adolescents is one of the major health problems of the contemporary youth. The aim of the study is to analyze the associations between mental load and physical activity (PA) in adolescents in school-day segments. METHODS: 381 adolescents (120 boys, 261 girls) took part in the research which was conducted in 19 secondary schools in the Czech Republic. Participants throughout the whole day (1-3 days) wore an ActiTrainer accelerometer that monitors PA and heart rate (HR). The reports covered 727 school days. The participants were divided into two groups with lower and higher mental load. RESULTS: Boys and girls with higher mental load in lessons do not compensate this load in neither volume nor intensity of PA during recess in greater amount than those who had lower mental load. In the individual school-day segments (apart from the time before school) no significant differences between the groups were found. CONCLUSION: When creating a habit of immediate compensation for mental load in lessons by PA, it is necessary to pay attention to boys and girls with higher mental load in lessons. The adoption of the habit should be supported by adequate physical literacy of both students and teachers and by changes in the school programme. PMID- 26849542 TI - Physical Activity and Sedentary Screen Time in Obese and Overweight Children Living in Different Environments. AB - AIM: To assess the relationship of children's physical activity and sedentary screen time with overweight and obesity in children living in different environments (town and city) in Lithuania. METHODS: An analysis of anthropometric data from 532 children living in town and city areas was performed. A youth physical activity questionnaire (YPAQ) was conducted to evaluate physical activity and sedentary screen time. RESULTS: The prevalence of overweight and obesity among the children was 25.5% in the town and 18.6% in the city. Children living in the town on average engaged 9.3 min/day less in moderate to vigorous physical activity (p=0.050) and had 33.2 MET-min/day lower energy expenditure than children living in the city. Sedentary screen time was extremely high on weekends in both town and city children. CONCLUSIONS: A higher prevalence of overweight and obesity and a lower amount of moderate-to-vigorous physical activity was found in children living in the town compared to children living in the city. PMID- 26849544 TI - Physical Activity and Screen-based Activity in Healthy Development of School-aged Children. AB - AIM: Physical and screen-based activity in adolescents plays a crucial role in future health outcomes. Therefore, the aim of the study was to examine the associations of physical activity and screen-based activity with behavioural and psychosocial characteristics of school-aged children. METHODS: Data on 11, 13 and 15 years old elementary school pupils (N=9,014; mean age=13.59) who participated in the cross-sectional Health Behaviour in School-aged Children 2009/2010 study in the Czech Republic and the Slovak Republic were analyzed. The associations of vigorous physical activity and screen-based activity with substance use, violent behaviour, eating habits and school-related outcomes adjusted for age were explored using logistic regression. RESULTS: Vigorous physical activity was positively associated with some of the health-related behaviours (smoking, breakfast consumption, vegetable and fruit consumption) and school related outcomes (perceived school achievement and school pressure), with gender and country based differences. Screen-based activity was significantly associated with all examined health-related behaviours and school related outcomes with only some country and gender based differences. CONCLUSIONS: Vigorous physical activity is positively associated with healthy development of adolescents. Screen based behaviour shows an inverse relationship with adolescents' healthy development, especially in the group of 11 and 13 years old children. Supporting physical activity conducive environments might lead to a reduction in screen based behaviour in adolescents and should be highlighted in health-promoting strategies. PMID- 26849545 TI - Effect of Physical Activity in Treatment of Paediatric Obesity. AB - The aim of the study was to compare the differences in anthropometric parameters, maximal oxygen uptake (VO2max) and physical activity (PA) between groups of 146 obese boys and 128 obese girls. We tried to describe the relationships between changes in PA and changes in VO2max, body fat, weight, waist circumference and hip circumference. We found statistically significant changes in VO2max and waist circumference only in the group of boys and significant changes in VO2max in the group of girls. PMID- 26849546 TI - The Impact of Physical Activity and Dietary Measures on the Biochemical and Anthropometric Parameters in Obese Children. Is There Any Genetic Predisposition? AB - AIM: The aim of the study was to monitor the importance of laboratory, anthropometric and genetic determination of the presence of risk factors for atherosclerosis, obesity, dyslipidemia and components of the metabolic syndrome in obese children and the response to dietary and regimen interventions in obese children. METHODS: As a part of the study, 353 paediatric patients (46% boys, 54% girls) with obesity and dyslipidemia, aged 8-16 years, participated in a one month lifestyle intervention programme. The programme involved a reduction of energy intake and supervised exercise programme consisting of 5 exercise units per day, each 50 minutes long. Standard biochemical methods were applied, including Lp-PLA2, as were anthropometric measurements and genetic analyses. RESULTS: During the reduction programme for the children there was a statistically significant decrease in all anthropometric indicators of bodyweight (p<0.001) as well as in lipid parameters and LpLPA2. Carriers of the FTO GG genotype and/or MC4R CC genotype lost significantly more body weight in comparison to non-carriers. CONCLUSION: Child obesity is an important social issue. After regimen interventions, there is weight loss as well as an improvement in biochemical parameters. There are individuals with a genetic predisposition for obesity, as well as individuals with a better response to regimen interventions which could, among other things, be determined by the FTO and MC4R genotypes. PMID- 26849547 TI - The effects of dance training program on the postural stability of middle aged women. AB - AIM: The aim of the study was to determine the effects of Greek folk dancing on postural stability in middle age women. METHODS: Sixty-three women aged from 47 53 participated in this study. All participants were randomly divided into the experimental group - 33 participants (mean +/- SD; body height=160.13 +/- 12.07 cm, body mass=63.81 +/- 10.56 kg), and the control group - 30 participants (mean +/- SD; body height=160.63 +/- 6.22 cm, body mass=64.79 +/- 8.19 kg). The following tests were used to evaluate the motor balance and posture stability of participants; the double-leg stance along the length of a balance beam (eyes open), the double-leg stance along the width of a balance beam (eyes open), the single-leg stance (eyes open) and the double-leg stance on one's toes (eyes closed). The Functional Reach Test for balance and the Star Excursion Balance Test were used to evaluate dynamic balance. RESULTS: The multivariate analysis of covariance of static and dynamic balance between participants of the experimental and control group at the final measuring, with neutralized differences at the initial measuring (Wilks' lambda=0.45), revealed a significant difference (p<0.05). The intergroup difference at the final measuring was also found to be significant (p<0.05) for the following variables; the double-leg stance on one's toes, the Functional Reach Test, balance of the right anterolateral, balance of the right posterolateral and balance of the left posteromedial. CONCLUSION: An organized dance activity programme does lead to the improvement of static and dynamic balance in middle aged women. PMID- 26849548 TI - Changing Views: Safety and Efficacy of Implantable Cardioverter- Defibrillator Therapy in Athletes. AB - The implantable cardioverter-defibrillator (ICD) is highly effective in reducing sudden death from ventricular tachyarrhythmia among high-risk cardiac patients. Conventional advice given to patients with ICD is to avoid physical activity more strenuous than playing golf or bowling. This recommendation is given due to a theoretical risk of arrhythmia precipitation, and thus increased risk of death due to failure to defibrillate, injury resulting from loss of control caused by arrhythmia-related syncope or shock, and also due to sport related direct damage to the ICD system. Recent prospective data from an international registry involving 372 athletes with ICDs in situ and actively participating in sports has been published. This indicates that, although physical activity resulted in an increased number of shocks compared to rest, there was no significant difference between intensive physical activity and any other activity (10% vs. 8%, p=0.34) in frequency of shocks. Furthermore, over a median follow-up period of 31 months (21-46 months), in the period of sports activity and 2 hour rest directly after there were no occurrences of death, resuscitated arrest or arrhythmia, or shock related injury. This data is likely to start a shift in every-day clinical decision-making leading to revision of the high level of precautions imposed on the rapidly enlarging ICD recipient population. PMID- 26849549 TI - Motives for Physical Activity among Adolescents in the Czech and Slovak Republics. AB - OBJECTIVES: Physical activity significantly contributes to overall health and the level of activity during adolescence has been associated with physical activity in adulthood. The aim of this paper was to analyse motives for young people undertaking leisure time physical activity in the Czech and Slovak Republics. METHODS: Eleven to fifteen year old schoolchildren (N=9,014; mean age=13.59) participating in the Health Behaviour in School-aged Children 2009/2010 study in the Czech and Slovak Republics completed 12 items measuring physical activity motivations. To analyse the factor structure of motives for physical activity, Confirmatory Factor Analysis (CFA) was conducted using Principal Component Analysis (PCA) with varimax rotation. RESULTS: Contrary to previous research that reported three main motives for physical activity (health, social, achievement), our study suggests four motives. The additional motive is a combination of internal and external motivations and was called the "Good Child Motive". CONCLUSIONS: Better understanding of motives behind physical activity or inactivity of young people could significantly contribute to evidence based planning and development of national strategies for public health and active living. PMID- 26849550 TI - Relationship between Czech Parent and Child Pedometer-assessed Weekday and Weekend Physical Activity and Screen Time. AB - AIM: Uncovering the influences of parents' behaviour on their children's physical activity provides an insight into the lifestyle of families and development of effective family-based interventions. The aim of this study was to determine the relationship between parents' behaviour (step count (SC) and screen time (ST)) and children's SC on weekdays and at weekends. METHODS: The participants (388 parents aged 35-45 and their 485 children aged 9-12) were randomly recruited from 21 Czech government funded primary schools. The participants recorded SC and ST duration for seven consecutive days (>= 10 h/day) during April-May and September October 2013. The associations between parents' behaviour (SC and ST) and children's SC were estimated using general linear regression separately for weekdays and weekends. Each 1,000 SC increase in mothers' (fathers') SC/weekday was associated with an extra 261 SC/day in their daughters and 413 (244) SC/day in their sons. RESULTS: Each 1,000 SC increase in mothers' (fathers') SC/weekend day was associated with an extra 523 (386) SC/day in their daughters and 508 (435) SC/day in their sons. A reduction in mothers' ST by 30 minutes per weekend day was associated with an extra 494 SC/day in their daughters and 467 SC/day in their sons. CONCLUSIONS: This study reveals a quantifiable relationship between parent-child SC/day and mothers' ST and children's SC at weekends. Weekend days are more suitable for the implementation of family-based interventions. PMID- 26849551 TI - Dramatic decrease in muscular fitness in the Czech schoolchildren over the Last 20 years. AB - AIM: Obesity and physical inactivity had already reached epidemic, becoming one of the leading causes of death and disability worldwide. The objective of this study was to investigate the current level and a nearly three decades' trend of muscular fitness (MF) and the nutritional state of Czech children. METHODS: In 2013, cross-sectional epidemiological survey was conducted in schoolchildren with examination of the anthropometric characteristics and measured MF using a UNIFIT test, which normative for MF categories was given as results of national monitoring data collected in 1987. In total 896 current schoolchildren (472 aged 8-9 years and 424 aged 12-13 years) were examined from selected children through stratified sampling from the Czech Republic. RESULTS: Against 31% of children from 1986 there were 74% of current children classified as "poor" or "below normal" in the MF category (p<0.001). MF was inversely associated with BMI. Poor posture was diagnosed in 24% of children, more frequently in overweight (OW) and obese (OB) children in comparison to normal body weight children (p<0.001). In comparison to 10% of OW and OB children in 1991, using these cut-off points for body mass index references, the current prevalence of OW and OB doubled (19.8%). CONCLUSIONS: Current Czech schoolchildren showed a doubled prevalence of OW and OB during the last two decades and simultaneously during nearly three decades there were more than doubled prevalence of "poor" or "under normal" MF of children, with overall dramatic decrease of MF in current schoolchildren. PMID- 26849552 TI - Sedentary Behaviour and Physical Activity of Randomised Sample of Czech Adults Aged 20-64 Years: IPAQ and GPAQ Studies between 2002 and 2011. AB - AIM: The prevalence of sedentary behaviour has increased, and physical activity (PA) levels have declined with increases in urbanisation and modernisation. Researchers need to find solutions to address this lack of PA. The main aim of this study was to identify the PA level and sedentary behaviour in a randomised sample of the Czech adult population in 2002 and 2011. METHODS: To investigate PA in 20-64 year old adults, the International Physical Activity Questionnaire (IPAQ) (in 2002) and the Global Physical Activity Questionnaire (GPAQ) (in 2011) were applied. The randomised samples comprised 1,782 participants in 2002, and 1,359 participants in 2011. RESULTS: The results showed a significant decrease (F=83.84; p<0.001; omega2=0.03) in the time spent sitting between the years 2002 and 2011. The proportion of individuals reporting low PA has increased (11.4% in 2002 vs. 27.9% in 2011). Individuals with college/university education were more likely to have low PA levels (OR=1.51, p<0.001, CI=1.21-1.68) compared with those with elementary or secondary education. Along with educational level, low PA levels are also associated with older age, spending more than four hours a day sitting, and the survey year. CONCLUSION: Sedentary behaviour, PA, and factors influencing this behaviour may differ across countries; therefore, more trend related research should be performed on these issues, especially in Central and Eastern Europe, where these studies are scarce. PMID- 26849554 TI - Association of Elevated High Sensitivity Cardiac Troponin T(hs-cTnT) Levels with Hemorrhagic Transformation and 3-Month Mortality in Acute Ischemic Stroke Patients with Rheumatic Heart Disease in China. AB - BACKGROUND AND OBJECTIVE: Elevated levels of high sensitivity cardiac troponin T (hs-cTnT) occur in a substantial proportion of patients with acute ischemic stroke (AIS) and can predict poor outcome and mortality after stroke. Whether elevated hs-cTnT levels can also predict hemorrhagic transformation (HT) or prognosis in AIS patients with rheumatic heart disease (RHD) remains unclear. METHODS: Data from the Chengdu Stroke Registry on consecutive AIS patients with RHD admitted to West China Hospital within 1 month of stroke onset from October 2011 to February 2014 were examined. Clinico-demographic characteristics, HT, functional outcomes and stroke recurrence were compared between patients with elevated hs-cTnT levels (>=14 ng/L) and patients with normal hs-cTnT levels (<14 ng/L). RESULTS: The final analysis involved 84 patients (31 males; mean age, 61.6+/-12.2 years), of whom serum hs-cTnT levels were elevated in 58.3%. Renal impairment was independently associated with elevated hs-cTnT levels (OR 4.184, 95%CI 1.17 to 15.01, P = 0.028), and patients with elevated hs-cTnT levels were at significantly higher risk of HT, 3-month mortality and 3-month disability/mortality (all P<=0.029). After controlling for age, sex, hypertension, renal impairment and National Institutes of Health Stroke Scale score on admission, the risk of HT and 3-month mortality was, respectively, 4.0- and 5.5-fold higher in patients with elevated hs-cTnT levels than in patients with normal hs-cTnT levels. CONCLUSION: Elevated hs-cTnT levels are independently associated with HT and 3-month mortality in AIS patients with RHD. These results with a small cohort should be verified and extended in large studies. PMID- 26849553 TI - Transcriptome Analysis of an Anthracnose-Resistant Tea Plant Cultivar Reveals Genes Associated with Resistance to Colletotrichum camelliae. AB - Tea plant breeding is a topic of great economic importance. However, disease remains a major cause of yield and quality losses. In this study, an anthracnose resistant cultivar, ZC108, was developed. An infection assay revealed different responses to Colletotrichum sp. infection between ZC108 and its parent cultivar LJ43. ZC108 had greater resistance than LJ43 to Colletotrichum camelliae. Additionally, ZC108 exhibited earlier sprouting in the spring, as well as different leaf shape and plant architecture. Microarray data revealed that the genes that are differentially expressed between LJ43 and ZC108 mapped to secondary metabolism-related pathways, including phenylpropanoid biosynthesis, phenylalanine metabolism, and flavonoid biosynthesis pathways. In addition, genes involved in plant hormone biosynthesis and signaling as well as plant-pathogen interaction pathways were also changed. Quantitative real-time PCR was used to examine the expression of 27 selected genes in infected and uninfected tea plant leaves. Genes encoding a MADS-box transcription factor, NBS-LRR disease resistance protein, and phenylpropanoid metabolism pathway components (CAD, CCR, POD, beta-glucosidase, ALDH and PAL) were among those differentially expressed in ZC108. PMID- 26849555 TI - CDKL5 and Shootin1 Interact and Concur in Regulating Neuronal Polarization. AB - In the last years, the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene has been associated with epileptic encephalopathies characterized by the early onset of intractable epilepsy, severe developmental delay, autistic features, and often the development of Rett syndrome-like features. Still, the role of CDKL5 in neuronal functions is not fully understood. By way of a yeast two hybrid screening we identified the interaction of CDKL5 with shootin1, a brain specific protein acting as a determinant of axon formation during neuronal polarization. We found evidence that CDKL5 is involved, at least in part, in regulating neuronal polarization through its interaction with shootin1. Indeed, the two proteins interact in vivo and both are localized in the distal tip of outgrowing axons. By using primary hippocampal neurons as model system we find that adequate CDKL5 levels are required for axon specification. In fact, a significant number of neurons overexpressing CDKL5 is characterized by supernumerary axons, while the silencing of CDKL5 disrupts neuronal polarization. Interestingly, shootin1 phosphorylation is reduced in neurons silenced for CDKL5 suggesting that the kinase affects, directly or indirectly, the post-translational modification of shootin1. Finally, we find that the capacity of CDKL5 to generate surplus axons is attenuated in neurons with reduced shootin1 levels, in agreement with the notion that two proteins act in a common pathway. Altogether, these results point to a role of CDKL5 in the early steps of neuronal differentiation that can be explained, at least in part, by its association with shootin1. PMID- 26849556 TI - Identifying Adult Dengue Patients at Low Risk for Clinically Significant Bleeding. AB - BACKGROUND: Clinically significant bleeding is important for subsequent optimal case management in dengue patients, but most studies have focused on dengue severity as an outcome. Our study objective was to identify differences in admission parameters between patients who developed clinically significant bleeding and those that did not. We sought to develop a model for discriminating between these patients. METHODS: We conducted a retrospective study of 4,383 adults aged >18 years who were hospitalized with dengue infection at Tan Tock Seng Hospital, Singapore from 2005 to 2008. Patients were divided into those with clinically significant bleeding (n = 188), and those without (n = 4,195). Demographic, clinical, and laboratory variables on admission were compared between groups to determine factors associated with clinically significant bleeding during hospitalization. RESULTS: On admission, female gender (p<0.001); temperature >38 degrees C (p<0.001); nausea/vomiting (p = 0.009) and abdominal pain/tenderness (p = 0.005); lower systolic blood pressure (p<0.001); higher pulse rate (p<0.001); increased absolute neutrophil count (ANC; p<0.001); reduced absolute lymphocyte count (ALC; p<0.001), haematocrit percentage (p<0.001) and platelet count (p = 0.04), and increased prothrombin time (p = 0.003) were significantly associated with clinically significant bleeding on univariate analysis. Multivariate analysis showed that independent variables in the final model were female gender (aOR 2.85; 95% CI: 1.9-4.33); temperature >38 degrees C (aOR 1.81; 95% CI: 1.27-2.61), nausea/vomiting (aOR 1.39; 95% CI: 0.94-2.12), ANC (aOR 1.3; 95% CI: 1.15-1.46), ALC (aOR 0.4; 95% CI: 0.25-0.64), hematocrit percentage (aOR 0.96; 95% CI: 0.92-1.002) and platelet count (aOR 0.993; 95% CI: 0.988-0.998). At the cutoff of -3.919, the model achieved an AUC of 0.758 (sensitivity:0.87, specificity: 0.38, PPV: 0.06, NPV: 0.98). CONCLUSION: Clinical risk factors associated with clinically significant bleeding were identified. This model may be useful to complement clinical judgement in triaging adult dengue patients given the dynamic nature of acute dengue, particularly in pre identifying those less likely to develop clinically significant bleeding. PMID- 26849557 TI - Correction: FOXP3+ Regulatory T Cells in Hepatic Fibrosis and Splenomegaly Caused by Schistosoma japonicum: The Spleen May Be a Major Source of Tregs in Subjects with Splenomegaly. PMID- 26849559 TI - Mechanical Intestinal Obstruction in a Porcine Model: Effects of Intra-Abdominal Hypertension. A Preliminary Study. AB - INTRODUCTION: Mechanical intestinal obstruction is a disorder associated with intra-abdominal hypertension and abdominal compartment syndrome. As the large intestine intraluminal and intra-abdominal pressures are increased, so the patient's risk for intestinal ischaemia. Previous studies have focused on hypoperfusion and bacterial translocation without considering the concomitant effect of intra-abdominal hypertension. The objective of this study was to design and evaluate a mechanical intestinal obstruction model in pigs similar to the human pathophysiology. MATERIALS AND METHODS: Fifteen pigs were divided into three groups: a control group (n = 5) and two groups of 5 pigs with intra abdominal hypertension induced by mechanical intestinal obstruction. The intra abdominal pressures of 20 mmHg were maintained for 2 and 5 hours respectively. Hemodynamic, respiratory and gastric intramucosal pH values, as well as blood tests were recorded every 30 min. RESULTS: Significant differences between the control and mechanical intestinal obstruction groups were noted. The mean arterial pressure, cardiac index, dynamic pulmonary compliance and abdominal perfusion pressure decreased. The systemic vascular resistance index, central venous pressure, pulse pressure variation, airway resistance and lactate increased within 2 hours from starting intra-abdominal hypertension (p<0.05). In addition, we observed increased values for the peak and plateau airway pressures, and low values of gastric intramucosal pH in the mechanical intestinal obstruction groups that were significant after 3 hours. CONCLUSION: The mechanical intestinal obstruction model appears to adequately simulate the pathophysiology of intestinal obstruction that occurs in humans. Monitoring abdominal perfusion pressure, dynamic pulmonary compliance, gastric intramucosal pH and lactate values may provide insight in predicting the effects on endorgan function in patients with mechanical intestinal obstruction. PMID- 26849558 TI - Causal Role of Alcohol Consumption in an Improved Lipid Profile: The Atherosclerosis Risk in Communities (ARIC) Study. AB - INTRODUCTION: Health benefits of low-to-moderate alcohol consumption may operate through an improved lipid profile. A Mendelian randomization (MR) approach was used to examine whether alcohol consumption causally affects lipid levels. METHODS: This analysis involved 10,893 European Americans (EA) from the Atherosclerosis Risk in Communities (ARIC) study. Common and rare variants in alcohol dehydrogenase and acetaldehyde dehydrogenase genes were evaluated for MR assumptions. Five variants, residing in the ADH1B, ADH1C, and ADH4 genes, were selected as genetic instruments and were combined into an unweighted genetic score. Triglycerides (TG), total cholesterol, high-density lipoprotein cholesterol (HDL-c) and its subfractions (HDL2-c and HDL3-c), low-density lipoprotein cholesterol (LDL-c), small dense LDL-c (sdLDL-c), apolipoprotein B (apoB), and lipoprotein (a) (Lp(a)) levels were analyzed. RESULTS: Alcohol consumption significantly increased HDL2-c and reduced TG, total cholesterol, LDL c, sdLDL-c, and apoB levels. For each of these lipids a non-linear trend was observed. Compared to the first quartile of alcohol consumption, the third quartile had a 12.3% lower level of TG (p < 0.001), a 7.71 mg/dL lower level of total cholesterol (p = 0.007), a 10.3% higher level of HDL2-c (p = 0.007), a 6.87 mg/dL lower level of LDL-c (p = 0.012), a 7.4% lower level of sdLDL-c (p = 0.037), and a 3.5% lower level of apoB (p = 0.058, poverall = 0.022). CONCLUSIONS: This study supports the causal role of regular low-to-moderate alcohol consumption in increasing HDL2-c, reducing TG, total cholesterol, and LDL c, and provides evidence for the novel finding that low-to-moderate consumption of alcohol reduces apoB and sdLDL-c levels among EA. However, given the nonlinearity of the effect of alcohol consumption, even within the range of low to-moderate drinking, increased consumption does not always result in a larger benefit. PMID- 26849562 TI - SMFM 2016: Meeting highlights-Friday (Podcast). PMID- 26849560 TI - Relationship between High Serum Cystatin C Levels and the Risk of Gestational Diabetes Mellitus. AB - AIMS: Serum cystatin C (CysC) has recently been shown to be associated with the incidence of type 2 diabetes mellitus (T2DM) and progression to the pre-diabetic state. The aim of this study was to explore the relationship between serum CysC and the risk of gestational diabetes mellitus (GDM) in Chinese pregnant women. METHODS: This cross-sectional study consisted of 400 pregnant women including 111 with GDM and 289 with normal glucose tolerance at 24-28 weeks of gestation. The subjects were further divided into four groups according to the CysC quartiles, and their clinical characteristics were compared. The serum CysC concentration was measured using immunoturbidimetry and the degree of insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Serum CysC levels were significantly higher in pregnant women with GDM than in the healthy pregnant women[1.0(0.8-1.8) vs 0.7(0.6-1.0), P<0.01). The Spearman's correlation analysis showed that serum CysC was positively associated with HOMA-IR(r = 0.118, P<0.05) and the occurrence of GDM(r = 0.348, P<0.01). The pregnant women were divided into quartiles according to their serum CysC concentrations. Compared to the first quartile, pregnant women in Q2 (OR, 2.441; P = 0.025), Q3 (OR, 3.383; P = 0.001) and Q4 (OR, 5.516; P<0.001) had higher risk of GDM after adjusted for age, BMI, HbA1c and HOMA-IR. Further, with a rise in the serum CysC, there was an increasing trend in the HOMA-IR levels (P<0.05). A binary logistic regression analysis after adjusting for other confounding variables revealed a significant and independent association between serum CysC and GDM [OR = 14.269; 95% confidence interval, 4.977-40.908, P<0.01].The receiver operating characteristic curve analysis revealed that the optimal cutoff point for serum CysC to indicate GDM was 0.95 mg/L. CONCLUSIONS: Serum CysC is significantly and independently associated with insulin resistance and GDM. It may be a helpful biomarker to identify the risk of GDM in Chinese pregnant women. PMID- 26849561 TI - The Impact of Comprehensive Case Management on HIV Client Outcomes. AB - In 1990, New York State instituted Comprehensive Medicaid Case Management, also known as Target Case Management (TCM), for people dealing with multiple comorbid conditions, including HIV. The goal of TCM is to assist clients in navigating the health care system to increase care engagement and treatment adherence for individuals with complex needs. HIV-positive individuals engaged in care are more likely to be virally suppressed, improving clinical outcomes and decreasing chances of HIV transmission. The purpose of this study was to understand the impact of TCM management on outcomes for people with HIV. Data were obtained from Amida Care, which operates not-for-profit managed care Medicaid and Medicare Special Needs Plans (SNPs) for HIV clients. Changes in clinical, cost, as well as medical and pharmacy utilization data among TCM clients were examined between January 2011 through September 2012 from the start of case management enrollment through the end of the study period (i.e., up to 6 months after disenrollment). Additionally, CD4 counts were compared between Amida Care TCM clients and non-TCM clients. Notable findings include increased CD4 counts for TCM clients over the one-year study period, achieving parity with non-TCM clients (i.e., Mean CD4 count > 500). When looking exclusively at TCM clients, there were increases in medication costs over time, which were concomitant with increased care engagement. Current findings demonstrate that TCM is able to achieve its goals of improving care engagement and treatment adherence. Subsequent policy changes resulting from the Affordable Care Act and the New York State Medicaid Redesign have made the Health Home the administrator of TCM services. Government entities charged with securing and managing TCM and care coordination for people with HIV should provide thoughtful and reasonable guidance and oversight in order to maintain optimal clinical outcomes for TCM clients and reduce the transmission of HIV. PMID- 26849563 TI - Insulin-Like Growth Factor-1 Levels in Term Newborns with Hypoxic-Ischemic Encephalopathy. AB - Objective This study aims to evaluate the correlation of changes in serum insulin like growth factor-1 (IGF-1) levels with the clinical staging of hypoxic-ischemic encephalopathy (HIE) in term newborns. Study Design A prospective study of 29 newborns with HIE (stage I = 15, stage II + III = 14) and 28 healthy term newborns as the control group was performed in the neonatal intensive care unit. IGF-1 levels were obtained within 6 hours after birth from HIE and control groups and again on day 3 from HIE group. HIE was classified using the Sarnat staging I to III. Results IGF-1 levels were significantly lower in the HIE group than in the control group (p = 0.024). It was lower in the HIE stage II to III group compared with HIE stage I group at birth (p < 0.0001) and on day 3 (p = 0.009). The mean IGF-1 levels were significantly higher on day 3 than on day 1 among stage II to III HIE (p = 0.006) and it was inversely correlated with staging (R = - 0.475, p = 0.009). There was a significant correlation between IGF-1 levels and Apgar score at 5 (R = 0.39, p = 0.042) and 10 minutes (R = 0.38, p = 0.035). Conclusions IGF-1 was lower in HIE and inversely correlated with clinical staging. It was increased with clinical improvement in the subsequent days. PMID- 26849564 TI - Mammalian Herbivores Alter the Population Growth and Spatial Establishment of an Early-Establishing Grassland Species. AB - Plant-herbivore interactions influence the establishment context of plant species, as herbivores alter the community context in which individual species establish, and the spatial relationship between individuals and their source population as plants invade. This relationship can be described using an establishment kernel, which takes into account movement through seed dispersal, and subsequent establishment of adults. Mammalian herbivores are hypothesized to influence plant population growth and establishment through a combination of consumption of seeds and seedlings, and movement of seeds. While the movement abilities of plants are well known, we have very few empirical mechanistic tests of how biotic factors like mammalian herbivores influence this spread potential. As herbivores of all sizes are abundant on the landscape, we asked the question, how do mammalian herbivores influence the population growth, spatial establishment, and the community establishment context of an early-recruiting native prairie legume, Chamaecrista fasciculata? We planted C. fasciculata in source populations within a four-acre tallgrass prairie restoration in plots with and without herbivores, and monitored its establishment with respect to distance from the source populations. We found that herbivores decreased population growth, and decreased the mean and range establishment distance. Additionally, C. fasciculata established more often without herbivores, and when surrounded by weedy, annual species. Our results provide insight into how the interactions between plants and herbivores can alter the spatial dynamics of developing plant communities, which is vital for colonization and range spread with fragmentation and climate change. Mammalian herbivores have the potential to both slow rates of establishment, but also determine the types of plant communities that surround invading species. Therefore, it is essential to consider the herbivore community when attempting to restore functioning plant communities. PMID- 26849565 TI - Comparison of Sample Preparation Methods Used for the Next-Generation Sequencing of Mycobacterium tuberculosis. AB - The advent and widespread application of next-generation sequencing (NGS) technologies to the study of microbial genomes has led to a substantial increase in the number of studies in which whole genome sequencing (WGS) is applied to the analysis of microbial genomic epidemiology. However, microorganisms such as Mycobacterium tuberculosis (MTB) present unique problems for sequencing and downstream analysis based on their unique physiology and the composition of their genomes. In this study, we compare the quality of sequence data generated using the Nextera and TruSeq isolate preparation kits for library construction prior to Illumina sequencing-by-synthesis. Our results confirm that MTB NGS data quality is highly dependent on the purity of the DNA sample submitted for sequencing and its guanine-cytosine content (or GC-content). Our data additionally demonstrate that the choice of library preparation method plays an important role in mitigating downstream sequencing quality issues. Importantly for MTB, the Illumina TruSeq library preparation kit produces more uniform data quality than the Nextera XT method, regardless of the quality of the input DNA. Furthermore, specific genomic sequence motifs are commonly missed by the Nextera XT method, as are regions of especially high GC-content relative to the rest of the MTB genome. As coverage bias is highly undesirable, this study illustrates the importance of appropriate protocol selection when performing NGS studies in order to ensure that sound inferences can be made regarding mycobacterial genomes. PMID- 26849566 TI - Crimson Spotted Rainbowfish (Melanotaenia duboulayi) Change Their Spatial Position according to Nutritional Requirement. AB - Decision making in moving animal groups has been shown to be disproportionately influenced by individuals at the front of groups. Therefore, an explanation of state-dependent positioning of individuals within animal groups may provide a mechanism for group movement decisions. Nutritional state is dynamic and can differ between members of the same group. It is also known to drive animal movement decisions. Therefore, we assayed 6 groups of 8 rainbowfish foraging in a flow tank. Half of the fish had been starved for 24h and half had been fed 1h prior to experimental start. Groups were assayed again one week later but individuals were allocated to the opposite nutritional treatment. During the assay the positions of individually identified fish were recorded as were the number of food items they each ate and the position within the group they acquired them from. Food-deprived fish were more often found towards the front of the shoal; the mean weighted positional score of food-deprived fish was significantly larger than that of well-fed fish. Individuals were not consistent in their position within a shoal between treatments. There was a significant positive correlation between mean weighted positional score and number of food items acquired which displays an obvious benefit to front positions. These results suggest that positional preferences are based on nutritional state and provide a mechanism for state-dependent influence on group decision-making as well as increasing our understanding of what factors are important for group functioning. PMID- 26849567 TI - Effect of Tobacco Control Policies on Information Seeking for Smoking Cessation in the Netherlands: A Google Trends Study. AB - BACKGROUND: The impact of tobacco control policies on measures of smoking cessation behaviour has often been studied, yet there is little information on their precise magnitude and duration. This study aims to measure the magnitude and timing of the impact of Dutch tobacco control policies on the rate of searching for information on smoking cessation, using Google Trends search query data. METHODS: An interrupted time series analysis was used to examine the effect of two types of policies (smoke-free legislation and reimbursement of smoking cessation support (SCS)) on Google searches for 'quit smoking'. Google Trends data were seasonally adjusted and analysed using autoregressive integrated moving average (ARIMA) modelling. Multiple effect periods were modelled as dummy variables and analysed simultaneously to examine the magnitude and duration of the effect of each intervention. The same analysis was repeated with Belgian search query data as a control group, since Belgium is the country most comparable to the Netherlands in terms of geography, language, history and culture. RESULTS: A significant increase in relative search volume (RSV) was found from one to four weeks (21-41%) after the introduction of the smoking ban in restaurants and bars in the Netherlands in 2008. The introduction of SCS reimbursement in 2011 was associated with a significant increase of RSV (16-22%) in the Netherlands after 3 to 52 weeks. The reintroduction of SCS in 2013 was associated with a significant increase of RSV (9-21%) in the Netherlands from 3 to 32 weeks after the intervention. No effects were found in the Belgian control group for the smoking ban and the reintroduction of SCS in 2013, but there was a significant increase in RSV shortly before and after the introduction of SCS in 2011. CONCLUSIONS: These findings suggest that these tobacco control policies have short-term or medium-term effects on the rate of searching for information on smoking cessation, and therefore potentially on smoking cessation rates. PMID- 26849568 TI - What Makes Sports Fans Interactive? Identifying Factors Affecting Chat Interactions in Online Sports Viewing. AB - Sports fans are able to watch games from many locations using TV services while interacting with other fans online. In this paper, we identify the factors that affect sports viewers' online interactions. Using a large-scale dataset of more than 25 million chat messages from a popular social TV site for baseball, we extract various game-related factors, and investigate the relationships between these factors and fans' interactions using a series of multiple regression analyses. As a result, we identify several factors that are significantly related to viewer interactions. In addition, we determine that the influence of these factors varies according to the user group; i.e., active vs. less active users, and loyal vs. non-loyal users. PMID- 26849569 TI - Preoperative Diagnostic Strategy for Parotid Gland Tumors Using Diffusion Weighted MRI and Technetium-99m Pertechnetate Scintigraphy: A Prospective Study. AB - OBJECTIVE: Fine needle aspiration cytology (FNAC) for diagnosis of a parotid gland tumor is widely used but its sensitivity is low and non-diagnostic rate is relatively high. In contrast, core needle biopsy (CNB) has a higher sensitivity and lower rate of sampling errors but has a higher risk of injury to adjacent organs such as facial nerve than FNAC. Screening of patients with parotid gland tumors to identify cases of pleomorphic adenoma (PA) and Warthin tumor (WT) may allow CNB to be confined to patients without PA and WT. We established an algorithm for preoperative diagnosis and management of parotid gland tumor using diffusion-weighted MRI and 99mTc pertechnetate scintigraphy. This algorithm was developed with the goal of maximal reduction of the number of patients in whom CNB is required. The purpose of the study is to validate our algorithm prospectively. METHODS: A prospective study was conducted in 71 cases who were newly diagnosed with parotid gland tumor and 53 cases were enrolled in the study. In the algorithm, PA (high apparent diffusion coefficient (ADC) mean>=1.5*10(-3) mm(2)/s) and non-PA (low ADCmean<1.5*10(-3) mm(2)/s) cases are first distinguished based on the ADCmean on diffusion-weighed MRI. Second, among suspected non-PA cases, WT and non-WT are distinguished using technetium-99m pertechnetate scintigraphy. CNB is then performed only in probable non-PA and non WT cases. RESULTS: Although CNB was only required in 40% (21/53) of all cases, we made a preoperative histopathological diagnosis with an accuracy of 87% (46/53) and we correctly diagnosed whether a tumor was benign or malignant with an accuracy of 96% (51/53). Preoperative surgical planning had to be changed during surgery in only one case (2%). CONCLUSIONS: Our algorithm is valuable in terms of clinical practice with highly potential for preoperative diagnosis and with less risk of CNB procedure. PMID- 26849570 TI - Multiple breath washout analysis in infants: quality assessment and recommendations for improvement. AB - Infant multiple breath washout (MBW) testing serves as a primary outcome in clinical studies. However, it is still unknown whether current software algorithms allow between-centre comparisons. In this study of healthy infants, we quantified MBW measurement errors and tried to improve data quality by simply changing software settings. We analyzed best quality MBW measurements performed with an ultrasonic flowmeter in 24 infants from two centres in Switzerland with the current software settings. To challenge the robustness of these settings, we also used alternative analysis approaches. Using the current analysis software, the coefficient of variation (CV) for functional residual capacity (FRC) differed significantly between centres (mean +/- SD (%): 9.8 +/- 5.6 and 5.8 +/- 2.9, respectively, p = 0.039). In addition, FRC values calculated during the washout differed between -25 and +30% from those of the washin of the same tracing. Results were mainly influenced by analysis settings and temperature recordings. Changing few algorithms resulted in significantly more robust analysis. Non-systematic inter-centre differences can be reduced by using correctly recorded environmental data and simple changes in the software algorithms. We provide implications that greatly improve infant MBW outcomes' quality and can be applied when multicentre trials are conducted. PMID- 26849572 TI - Fusion and Thermal Degradation Behavior of Symmetric Sulfur-Containing Quaternary Ammonium Bromides. AB - Quaternary ammonium salts are widely used in consumer products and industrial processes, where their instability at elevated temperatures limits their range of applications. In this work, the thermal behavior of a new class of quaternary ammonium salts was investigated using differential scanning calorimetry. These salts contain a sulfur atom in each chain at the fourth position from the central nitrogen and are thus termed thiaquats. The temperatures at which these salts melt and thermally degrade were determined, and enthalpies and entropies of fusion were evaluated. Their melting points increase with chain lengths, in contrast to the behavior of traditional quaternary ammonium salts. Furthermore, they exhibit enthalpies and entropies of fusion significantly lower than corresponding tetraalkyl analogues. These trends provide physical insight into the molecular-level behavior of these salts, suggesting that they do not fully dissociate upon melting. The thiaquats also exhibit thermal stability to markedly higher temperatures than traditional quaternary ammonium bromides, a phenomenon that can be explained in by strong pairing between the quaternary cation and bromide anion, which inhibits possible decomposition mechanisms. This enhanced thermal stability may enable applications of these salts in processes where traditional salts are not viable, such as phase-transfer-catalyzed systems performed at elevated temperatures. PMID- 26849571 TI - On Nature's Strategy for Assigning Genetic Code Multiplicity. AB - Genetic code redundancy would yield, on the average, the assignment of three codons for each of the natural amino acids. The fact that this number is observed only for incorporating Ile and to stop RNA translation still waits for an overall explanation. Through a Structural Bioinformatics approach, the wealth of information stored in the Protein Data Bank has been used here to look for unambiguous clues to decipher the rationale of standard genetic code (SGC) in assigning from one to six different codons for amino acid translation. Leu and Arg, both protected from translational errors by six codons, offer the clearest clue by appearing as the most abundant amino acids in protein-protein and protein nucleic acid interfaces. Other SGC hidden messages have been sought by analyzing, in a protein structure framework, the roles of over- and under-protected amino acids. PMID- 26849573 TI - Effects of dentifrices differing in fluoride compounds on artificial enamel caries lesions in vitro. AB - The aim of this study was to compare the caries-preventive effect of a stabilized stannous fluoride/sodium fluoride dentifrice containing sodium hexametaphosphate with those of a regular, solely sodium fluoride-containing and amine fluoride containing dentifrice on pre-demineralized bovine enamel specimens using a pH cycling model. Bovine enamel specimens with two artificial lesions each were prepared. Baseline mineral loss of both lesions was analyzed using transversal microradiography (TMR). Eighty-five specimens with a mean (SD) baseline mineral loss of 3393 (683) vol% * um were selected and randomly allocated to five groups (n = 13/15). Treatments during pH-cycling (28 days and 2 * 20 min demineralization/day) were: brushing twice daily with slurries of AmF (1400 ppm F ), NaF (1450 ppm F-), SnF2/NaF (1100 ppm F-/350 ppm F-), and fluoride-free (FF) dentifrices or they were immersed in distilled water and remained unbrushed (NB). Subsequently, from each specimen one lesion was covered with acid-resistant varnish, while the remaining lesion was demineralized for another 14 days. Differences in integrated mineral loss (??Z) were calculated between values before and after pH-cycling (??Z E1) as well as before pH-cycling and after second demineralization (??Z E2) using TMR. Treatments AmF and NaF induced a significantly higher mineral gain (??Z E1/??Z E2) compared to treatments FF and NB (p < 0.05; ANOVA test). Except for treatments AmF and NaF no significant differences in mineral loss between before and after pH-cycling could be observed (p < 0.05; t test) [??Z E1: AmF:1563 (767); NaF:1222 (1246); SnF2/NaF:258 (1259); FF:-52 (1223); NB:-151 (834)]. Both dentifrices with either AmF or NaF promoted remineralization, whereas SnF2/NaF dentifrice did not promote remineralization in a biofilm-free pH-cycling model. PMID- 26849576 TI - Random Free Fermions: An Analytical Example of Eigenstate Thermalization. AB - Having analytical instances of the eigenstate thermalization hypothesis (ETH) is of obvious interest, both for fundamental and applied reasons. This is generally a hard task, due to the belief that nonlinear interactions are basic ingredients of the thermalization mechanism. In this article we prove that random Gaussian free fermions satisfy ETH in the multiparticle sector, by analytically computing the correlations and entanglement entropies of the theory. With the explicit construction at hand, we finally comment on the differences between fully random Hamiltonians and random Gaussian systems, providing a physically motivated notion of randomness of the microscopic quantum state. PMID- 26849577 TI - Cooling of a One-Dimensional Bose Gas. AB - We experimentally study the dynamics of a degenerate one-dimensional Bose gas that is subject to a continuous outcoupling of atoms. Although standard evaporative cooling is rendered ineffective by the absence of thermalizing collisions in this system, we observe substantial cooling. This cooling proceeds through homogeneous particle dissipation and many-body dephasing, enabling the preparation of otherwise unexpectedly low temperatures. Our observations establish a scaling relation between temperature and particle number, and provide insights into equilibration in the quantum world. PMID- 26849575 TI - Parasympathetic Vagal Control of Cardiac Function. AB - This brief review focuses on four new topics, with novel and clinically significant consequences, concerning the powerful influence of parasympathetic activity on cardiac function. In this short summary, we will highlight very recent and important work, published in the last 3-4 years, that (1) challenges the paradigm that parasympathetic activity to the heart is involved in the control of heart rate but plays little role in other cardiac functions, (2) characterizes important long-range synaptic pathways to parasympathetic cardiac vagal neurons that are involved in "higher" brain functions (such as arousal and emotional challenges), (3) asks whether implantable chronic vagal nerve stimulation is a promising clinical tool for treating cardiovascular diseases, and (4) describes newly identified neuropeptides and other modulators that can influence the generation and maintenance of parasympathetic activity to the heart. PMID- 26849578 TI - Dissipative Remote-State Preparation in an Interacting Medium. AB - Standard quantum state preparation methods work by preparing a required state locally and then distributing it to a distant location by a free-space propagation. We instead study procedures of preparing a target state at a remote location in the presence of an interacting background medium on which no control is required, manipulating only local dissipation. In mathematical terms, we characterize a set of reduced steady states stabilizable by local dissipation. An explicit local method is proposed by which one can construct a wanted one-site reduced steady state at an arbitrary remote site in a lattice of any size and geometry. In the chain geometry we also prove uniqueness of such a steady state. We demonstrate that the convergence time to fixed precision is smaller than the inverse gap, and we study robustness of the scheme in different medium interactions. PMID- 26849574 TI - Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study. AB - BACKGROUND: Myotonic Dystrophy type 1 (DM1) is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported. Our aim is to study gender impact on DM1 phenotype and severity. METHODS: We first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (>18 y) from the DM-Scope nationwide registry and observed different patterns in males and females. Then, we assessed gender impact on social and economic domains using the AFM-Telethon DM1 survey (n = 970), and morbidity and mortality using the French National Health Service Database (n = 3301). RESULTS: Men more frequently had (1) severe muscular disability with marked myotonia, muscle weakness, cardiac, and respiratory involvement; (2) developmental abnormalities with facial dysmorphism and cognitive impairment inferred from low educational levels and work in specialized environments; and (3) lonely life. Alternatively, women more frequently had cataracts, dysphagia, digestive tract dysfunction, incontinence, thyroid disorder and obesity. Most differences were out of proportion to those observed in the general population. Compared to women, males were more affected in their social and economic life. In addition, they were more frequently hospitalized for cardiac problems, and had a higher mortality rate. CONCLUSION: Gender is a previously unrecognized factor influencing DM1 clinical profile and severity of the disease, with worse socio-economic consequences of the disease and higher morbidity and mortality in males. Gender should be considered in the design of both stratified medical management and clinical trials. PMID- 26849579 TI - Quantum Enhanced Estimation of a Multidimensional Field. AB - We present a framework for the quantum enhanced estimation of multiple parameters corresponding to noncommuting unitary generators. Our formalism provides a recipe for the simultaneous estimation of all three components of a magnetic field. We propose a probe state that surpasses the precision of estimating the three components individually, and we discuss measurements that come close to attaining the quantum limit. Our study also reveals that too much quantum entanglement may be detrimental to attaining the Heisenberg scaling in the estimation of unitarily generated parameters. PMID- 26849581 TI - Sound of Dark Matter: Searching for Light Scalars with Resonant-Mass Detectors. AB - The fine-structure constant and the electron mass in string theory are determined by the values of scalar fields called moduli. If the dark matter takes on the form of such a light modulus, it oscillates with a frequency equal to its mass and an amplitude determined by the local dark-matter density. This translates into an oscillation of the size of a solid that can be observed by resonant-mass antennas. Existing and planned experiments, combined with a dedicated resonant mass detector proposed in this Letter, can probe dark-matter moduli with frequencies between 1 kHz and 1 GHz, with much better sensitivity than searches for fifth forces. PMID- 26849580 TI - Testing General Relativity with the Shadow Size of Sgr A(*). AB - In general relativity, the angular radius of the shadow of a black hole is primarily determined by its mass-to-distance ratio and depends only weakly on its spin and inclination. If general relativity is violated, however, the shadow size may also depend strongly on parametric deviations from the Kerr metric. Based on a reconstructed image of Sagittarius A^{*} (Sgr A^{*}) from a simulated one-day observing run of a seven-station Event Horizon Telescope (EHT) array, we employ a Markov chain Monte Carlo algorithm to demonstrate that such an observation can measure the angular radius of the shadow of Sgr A^{*} with an uncertainty of ~1.5 MUas (6%). We show that existing mass and distance measurements can be improved significantly when combined with upcoming EHT measurements of the shadow size and that tight constraints on potential deviations from the Kerr metric can be obtained. PMID- 26849582 TI - Dark Matter Velocity Spectroscopy. AB - Dark matter decays or annihilations that produce linelike spectra may be smoking gun signals. However, even such distinctive signatures can be mimicked by astrophysical or instrumental causes. We show that velocity spectroscopy-the measurement of energy shifts induced by relative motion of source and observer can separate these three causes with minimal theoretical uncertainties. The principal obstacle has been energy resolution, but upcoming experiments will have the precision needed. As an example, we show that the imminent Astro-H mission can use Milky Way observations to separate possible causes of the 3.5-keV line. We discuss other applications. PMID- 26849585 TI - Scale-Invariant Resummed Perturbation at Finite Temperatures. AB - We use the scalar model with quartic interaction to illustrate how a nonperturbative variational technique combined with renormalization group (RG) properties efficiently resums perturbative expansions in thermal field theories. The resulting convergence and scale dependence of optimized thermodynamical quantities, here illustrated up to two-loop order, are drastically improved as compared to standard perturbative expansions, as well as to other related methods such as the screened perturbation or (resummed) hard-thermal-loop perturbation, that miss RG invariance (as we explain). Being very general and easy to implement, our method is a potential analytical alternative to dealing with the phase transitions of field theories such as thermal QCD. PMID- 26849584 TI - Inflatable Dark Matter. AB - We describe a general scenario, dubbed "inflatable dark matter," in which the density of dark matter particles can be reduced through a short period of late time inflation in the early Universe. The overproduction of dark matter that is predicted within many, otherwise, well-motivated models of new physics can be elegantly remedied within this context. Thermal relics that would, otherwise, be disfavored can easily be accommodated within this class of scenarios, including dark matter candidates that are very heavy or very light. Furthermore, the nonthermal abundance of grand unified theory or Planck scale axions can be brought to acceptable levels without invoking anthropic tuning of initial conditions. A period of late-time inflation could have occurred over a wide range of scales from ~MeV to the weak scale or above, and could have been triggered by physics within a hidden sector, with small but not necessarily negligible couplings to the standard model. PMID- 26849583 TI - Improved Constraints on Cosmology and Foregrounds from BICEP2 and Keck Array Cosmic Microwave Background Data with Inclusion of 95 GHz Band. AB - We present results from an analysis of all data taken by the BICEP2 and Keck Array cosmic microwave background (CMB) polarization experiments up to and including the 2014 observing season. This includes the first Keck Array observations at 95 GHz. The maps reach a depth of 50 nK deg in Stokes Q and U in the 150 GHz band and 127 nK deg in the 95 GHz band. We take auto- and cross spectra between these maps and publicly available maps from WMAP and Planck at frequencies from 23 to 353 GHz. An excess over lensed LambdaCDM is detected at modest significance in the 95*150 BB spectrum, and is consistent with the dust contribution expected from our previous work. No significant evidence for synchrotron emission is found in spectra such as 23*95, or for correlation between the dust and synchrotron sky patterns in spectra such as 23*353. We take the likelihood of all the spectra for a multicomponent model including lensed LambdaCDM, dust, synchrotron, and a possible contribution from inflationary gravitational waves (as parametrized by the tensor-to-scalar ratio r) using priors on the frequency spectral behaviors of dust and synchrotron emission from previous analyses of WMAP and Planck data in other regions of the sky. This analysis yields an upper limit r_{0.05}<0.09 at 95% confidence, which is robust to variations explored in analysis and priors. Combining these B-mode results with the (more model-dependent) constraints from Planck analysis of CMB temperature plus baryon acoustic oscillations and other data yields a combined limit r_{0.05}<0.07 at 95% confidence. These are the strongest constraints to date on inflationary gravitational waves. PMID- 26849586 TI - Magnetic Corrections to the Soft Photon Theorem. AB - The soft photon theorem, in its standard form, requires corrections when the asymptotic particle states carry magnetic charges. These corrections are deduced using electromagnetic duality and the resulting soft formula conjectured to be exact for all Abelian gauge theories. Recent work has shown that the standard soft theorem implies an infinity of conserved electric charges. The associated symmetries are identified as "large" electric gauge transformations. Here the magnetic corrections to the soft theorem are shown to imply a second infinity of conserved magnetic charges. The associated symmetries are identified as large magnetic gauge transformations. The large magnetic symmetries are naturally subsumed in a complexification of the electric ones. PMID- 26849589 TI - Relativistic and Nuclear Medium Effects on the Coulomb Sum Rule. AB - In light of the forthcoming high precision quasielastic electron scattering data from Jefferson Lab, it is timely for the various approaches to nuclear structure to make robust predictions for the associated response functions. With this in mind, we focus here on the longitudinal response function and the corresponding Coulomb sum rule for isospin-symmetric nuclear matter at various baryon densities. Using a quantum field-theoretic quark-level approach which preserves the symmetries of quantum chromodynamics, as well as exhibiting dynamical chiral symmetry breaking and quark confinement, we find a dramatic quenching of the Coulomb sum rule for momentum transfers |q|?0.5 GeV. The main driver of this effect lies in changes to the proton Dirac form factor induced by the nuclear medium. Such a dramatic quenching of the Coulomb sum rule was not seen in a recent quantum Monte Carlo calculation for carbon, suggesting that the Jefferson Lab data may well shed new light on the explicit role of QCD in nuclei. PMID- 26849591 TI - Phase-Stable Free-Space Optical Lattices for Trapped Ions. AB - We demonstrate control of the absolute phase of an optical lattice with respect to a single trapped ion. The lattice is generated by off-resonant free-space laser beams, and we actively stabilize its phase by measuring its ac-Stark shift on a trapped ion. The ion is localized within the standing wave to better than 2% of its period. The locked lattice allows us to apply displacement operations via resonant optical forces with a controlled direction in phase space. Moreover, we observe the lattice-induced phase evolution of spin superposition states in order to analyze the relevant decoherence mechanisms. Finally, we employ lattice induced phase shifts for inferring the variation of the ion position over the 157 MUm range along the trap axis at accuracies of better than 6 nm. PMID- 26849593 TI - Positronium Confinement in Small Cavities: A Two-Particle Model for the Lowering of Contact Density. AB - Positronium (Ps) is widely used as a probe for studying nanometric porosities in condensed matter. Accessible experimental measurements concern annihilation rates by pickoff processes and contact densities (the electron density at the positron position). Existing models for describing Ps properties in small cavities do not justify the lowering of the contact density with respect to that of Ps in vacuum, as found in most materials. We formulate a two-particle model in which only the electron is confined in the cavity, while the positron is moving freely and feels the medium via a positive work function. Our calculation fully explains experimental data for a large class of materials and suggests a way to gain information on pore sizes and positron work functions. PMID- 26849592 TI - Entanglement and Bell Correlation in Electron-Exchange Collisions. AB - Elastic collisions between initially unpolarized electrons and hydrogenlike atoms are discussed, aiming to analyze the entanglement properties of the correlated final spin system. Explicit spin-dependent interactions are neglected and electron exchange only is taken into account. We show the final spin system to be completely characterized by a single spin correlation parameter depending on scattering angle and energy. Its numerical value identifies the final spins of the collision partners to be either in the separable, entangled, or Bell correlated regions. We emphasize explicit examples for the mixed spin system in order to illustrate the abstract concepts. The analysis of published experimental and numerical data reveals the possibility to create tunable pairs of collision partners with any desired degree of spin entanglement. PMID- 26849588 TI - Simple Nuclear Structure in (111-129)Cd from Atomic Isomer Shifts. AB - Isomer shifts have been determined in ^{111-129}Cd by high-resolution laser spectroscopy at CERN-ISOLDE. The corresponding mean square charge-radii changes, from the 1/2^{+} and the 3/2^{+} ground states to the 11/2^{-} isomers, have been found to follow a distinct parabolic dependence as a function of the atomic mass number. Since the isomers have been previously associated with simplicity due to the linear mass dependence of their quadrupole moments, the regularity of the isomer shifts suggests a higher order of symmetry affecting the ground states in addition. A comprehensive description assuming nuclear deformation is found to accurately reproduce the radii differences in conjunction with the known quadrupole moments. This intuitive interpretation is supported by covariant density functional theory. PMID- 26849590 TI - Ionization Avalanching in Clusters Ignited by Extreme-Ultraviolet Driven Seed Electrons. AB - We study the ionization dynamics of Ar clusters exposed to ultrashort near infrared (NIR) laser pulses for intensities well below the threshold at which tunnel ionization ignites nanoplasma formation. We find that the emission of highly charged ions up to Ar^{8+} can be switched on with unit contrast by generating only a few seed electrons with an ultrashort extreme-ultraviolet (XUV) pulse prior to the NIR field. Molecular dynamics simulations can explain the experimental observations and predict a generic scenario where efficient heating via inverse bremsstrahlung and NIR avalanching is followed by resonant collective nanoplasma heating. The temporally and spatially well-controlled injection of the XUV seed electrons opens new routes for controlling avalanching and heating phenomena in nanostructures and solids, with implications for both fundamental and applied laser-matter science. PMID- 26849594 TI - Exploring Dephasing of a Solid-State Quantum Emitter via Time- and Temperature Dependent Hong-Ou-Mandel Experiments. AB - We probe the indistinguishability of photons emitted by a semiconductor quantum dot (QD) via time- and temperature-dependent two-photon interference (TPI) experiments. An increase in temporal separation between consecutive photon emission events reveals a decrease in TPI visibility on a nanosecond time scale, theoretically described by a non-Markovian noise process in agreement with fluctuating charge traps in the QD's vicinity. Phonon-induced pure dephasing results in a decrease in TPI visibility from (96+/-4)% at 10 K to a vanishing visibility at 40 K. In contrast to Michelson-type measurements, our experiments provide direct access to the time-dependent coherence of a quantum emitter on a nanosecond time scale. PMID- 26849595 TI - Partially Nondestructive Continuous Detection of Individual Traveling Optical Photons. AB - We report the continuous and partially nondestructive measurement of optical photons. For a weak light pulse traveling through a slow-light optical medium (signal), the associated atomic-excitation component is detected by another light beam (probe) with the aid of an optical cavity. We observe strong correlations of g_{sp}^{(2)}=4.4(5) between the transmitted signal and probe photons. The observed (intrinsic) conditional nondestructive quantum efficiency ranges between 13% and 1% (65% and 5%) for a signal transmission range of 2% to 35%, at a typical time resolution of 2.5 MUs. The maximal observed (intrinsic) device nondestructive quantum efficiency, defined as the product of the conditional nondestructive quantum efficiency and the signal transmission, is 0.5% (2.4%). The normalized cross-correlation function violates the Cauchy-Schwarz inequality, confirming the nonclassical character of the correlations. PMID- 26849596 TI - Suppressing Spectral Diffusion of Emitted Photons with Optical Pulses. AB - In many quantum architectures the solid-state qubits, such as quantum dots or color centers, are interfaced via emitted photons. However, the frequency of photons emitted by solid-state systems exhibits slow uncontrollable fluctuations over time (spectral diffusion), creating a serious problem for implementation of the photon-mediated protocols. Here we show that a sequence of optical pulses applied to the solid-state emitter can stabilize the emission line at the desired frequency. We demonstrate efficiency, robustness, and feasibility of the method analytically and numerically. Taking nitrogen-vacancy center in diamond as an example, we show that only several pulses, with the width of 1 ns, separated by few ns (which is not difficult to achieve) can suppress spectral diffusion. Our method provides a simple and robust way to greatly improve the efficiency of photon-mediated entanglement and/or coupling to photonic cavities for solid-state qubits. PMID- 26849597 TI - Spontaneous Symmetry Breaking and Phase Coherence of a Photon Bose-Einstein Condensate Coupled to a Reservoir. AB - We examine the phase evolution of a Bose-Einstein condensate of photons generated in a dye microcavity by temporal interference with a phase reference. The photoexcitable dye molecules constitute a reservoir of variable size for the condensate particles, allowing for grand canonical statistics with photon bunching, as in a lamp-type source. We directly observe phase jumps of the condensate associated with the large statistical number fluctuations and find a separation of correlation time scales. For large systems, our data reveal phase coherence and a spontaneously broken symmetry, despite the statistical fluctuations. PMID- 26849598 TI - Walk-Off-Induced Modulation Instability, Temporal Pattern Formation, and Frequency Comb Generation in Cavity-Enhanced Second-Harmonic Generation. AB - We derive a time-domain mean-field equation to model the full temporal and spectral dynamics of light in singly resonant cavity-enhanced second-harmonic generation systems. We show that the temporal walk-off between the fundamental and the second-harmonic fields plays a decisive role under realistic conditions, giving rise to rich, previously unidentified nonlinear behavior. Through linear stability analysis and numerical simulations, we discover a new kind of quadratic modulation instability which leads to the formation of optical frequency combs and associated time-domain dissipative structures. Our numerical simulations show excellent agreement with recent experimental observations of frequency combs in quadratic nonlinear media [Phys. Rev. A 91, 063839 (2015)]. Thus, in addition to unveiling a new, experimentally accessible regime of nonlinear dynamics, our work enables predictive modeling of frequency comb generation in cavity-enhanced second-harmonic generation systems. We expect our findings to have wide impact on the study of temporal and spectral dynamics in a diverse range of dispersive, quadratically nonlinear resonators. PMID- 26849599 TI - Unveiling Temporal Correlations Characteristic of a Phase Transition in the Output Intensity of a Fiber Laser. AB - We use advanced statistical tools of time-series analysis to characterize the dynamical complexity of the transition to optical wave turbulence in a fiber laser. Ordinal analysis and the horizontal visibility graph applied to the experimentally measured laser output intensity reveal the presence of temporal correlations during the transition from the laminar to the turbulent lasing regimes. Both methods unveil coherent structures with well-defined time scales and strong correlations both, in the timing of the laser pulses and in their peak intensities. Our approach is generic and may be used in other complex systems that undergo similar transitions involving the generation of extreme fluctuations. PMID- 26849600 TI - Synthetic Spin-Orbit Coupling in an Optical Lattice Clock. AB - We propose the use of optical lattice clocks operated with fermionic alkaline earth atoms to study spin-orbit coupling (SOC) in interacting many-body systems. The SOC emerges naturally during the clock interrogation, when atoms are allowed to tunnel and accumulate a phase set by the ratio of the "magic" lattice wavelength to the clock transition wavelength. We demonstrate how standard protocols such as Rabi and Ramsey spectroscopy that take advantage of the sub Hertz resolution of state-of-the-art clock lasers can perform momentum-resolved band tomography and determine SOC-induced s-wave collisions in nuclear-spin polarized fermions. With the use of a second counterpropagating clock beam, we propose a method for engineering controlled atomic transport and study how it is modified by p- and s-wave interactions. The proposed spectroscopic probes provide clean and well-resolved signatures at current clock operating temperatures. PMID- 26849601 TI - Acoustic Emission from Breaking a Bamboo Chopstick. AB - The acoustic emission from breaking a bamboo chopstick or a bundle of spaghetti is found to exhibit similar behavior as the famous seismic laws of Gutenberg and Richter, Omori, and Bath. By the use of a force-sensing detector, we establish a positive correlation between the statistics of sound intensity and the magnitude of a tremor. We also manage to derive these laws analytically without invoking the concept of a phase transition, self-organized criticality, or fractal. Our model is deterministic and relies on the existence of a structured cross section, either fibrous or layered. This success at explaining the power-law behavior supports the proposal that geometry is sometimes more important than mechanics. PMID- 26849602 TI - Anomalously Soft Non-Euclidean Springs. AB - In this work we study the mechanical properties of a frustrated elastic ribbon spring-the non-Euclidean minimal spring. This spring belongs to the family of non Euclidean plates: it has no spontaneous curvature, but its lateral intrinsic geometry is described by a non-Euclidean reference metric. The reference metric of the minimal spring is hyperbolic, and can be embedded as a minimal surface. We argue that the existence of a continuous set of such isometric minimal surfaces with different extensions leads to a complete degeneracy of the bulk elastic energy of the minimal spring under elongation. This degeneracy is removed only by boundary layer effects. As a result, the mechanical properties of the minimal spring are unusual: the spring is ultrasoft with a rigidity that depends on the thickness t as t^{7/2} and does not explicitly depend on the ribbon's width. Moreover, we show that as the ribbon is widened, the rigidity may even decrease. These predictions are confirmed by a numerical study of a constrained spring. This work is the first to address the unusual mechanical properties of constrained non-Euclidean elastic objects. PMID- 26849603 TI - Collective Atomic Displacements during Complex Phase Boundary Migration in Solid Solid Phase Transformations. AB - The A15 to bcc phase transition is simulated at the atomic scale based on an interatomic potential for molybdenum. The migration of the phase boundary proceeds via long-range collective displacements of entire groups of atoms across the interface. To capture the kinetics of these complex atomic rearrangements over extended time scales we use the adaptive kinetic Monte Carlo approach. An effective barrier of 0.5 eV is determined for the formation of each new bcc layer. This barrier is not associated with any particular atomistic process that governs the dynamics of the phase boundary migration. Instead, the effective layer transformation barrier represents a collective property of the complex potential energy surface. PMID- 26849604 TI - Random Field Driven Spatial Complexity at the Mott Transition in VO(2). AB - We report the first application of critical cluster techniques to the Mott metal insulator transition in vanadium dioxide. We show that the geometric universal properties of the metallic and insulating puddles observed by scanning near-field infrared microscopy are consistent with the system passing near criticality of the random field Ising model as temperature is varied. The resulting large barriers to equilibrium may be the source of the unusually robust hysteresis phenomena associated with the metal-insulator transition in this system. PMID- 26849606 TI - Voltage Quench Dynamics of a Kondo System. AB - We examine the dynamics of a correlated quantum dot in the mixed valence regime. We perform numerically exact calculations of the current after a quantum quench from equilibrium by rapidly applying a bias voltage in a wide range of initial temperatures. The current exhibits short equilibration times and saturates upon the decrease of temperature at all times, indicating Kondo behavior both in the transient regime and in the steady state. The time-dependent current saturation temperature connects the equilibrium Kondo temperature to a substantially increased value at voltages outside of the linear response. These signatures are directly observable by experiments in the time domain. PMID- 26849605 TI - Unraveling Photoinduced Spin Dynamics in the Topological Insulator Bi(2)Se(3). AB - We report on a time-resolved ultrafast optical spectroscopy study of the topological insulator Bi_{2}Se_{3}. We unravel that a net spin polarization cannot only be generated using circularly polarized light via interband transitions between topological surface states (SSs), but also via transitions between SSs and bulk states. Our experiment demonstrates that tuning photon energy or temperature can essentially allow for photoexcitation of spin-polarized electrons to unoccupied topological SSs with two distinct spin relaxation times (~25 and ~300 fs), depending on the coupling between SSs and bulk states. The intrinsic mechanism leading to such distinctive spin dynamics is the scattering in SSs and bulk states which is dominated by E_{g}^{2} and A_{1g}^{1} phonon modes, respectively. These findings are suggestive of novel ways to manipulate the photoinduced coherent spins in topological insulators. PMID- 26849607 TI - Narrow-Line Single-Molecule Transducer between Electronic Circuits and Surface Plasmons. AB - A molecular wire containing an emitting molecular center is controllably suspended between the plasmonic electrodes of a cryogenic scanning tunneling microscope. Passing current through this circuit generates an ultranarrow-line emission at an energy of ~1.5 eV which is assigned to the fluorescence of the molecular center. Control over the linewidth is obtained by progressively detaching the emitting unit from the surface. The recorded spectra also reveal several vibronic peaks of low intensities that can be viewed as a fingerprint of the emitter. Surface plasmons localized at the tip-sample interface are shown to play a major role in both excitation and emission of the molecular excitons. PMID- 26849608 TI - Anomalous Quasiparticle Symmetries and Non-Abelian Defects on Symmetrically Gapped Surfaces of Weak Topological Insulators. AB - We show that boundaries of 3D weak topological insulators can become gapped by strong interactions while preserving all symmetries, leading to Abelian surface topological order. The anomalous nature of weak topological insulator surfaces manifests itself in a nontrivial action of symmetries on the quasiparticles; most strikingly, translations change the anyon types in a manner impossible in strictly 2D systems with the same symmetry. As a further consequence, screw dislocations form non-Abelian defects that trap Z_{4} parafermion zero modes. PMID- 26849609 TI - Effect of Impurities on the Josephson Current through Helical Metals: Exploiting a Neutrino Paradigm. AB - In this Letter we study the effect of time-reversal symmetric impurities on the Josephson supercurrent through two-dimensional helical metals such as on a topological insulator surface state. We show that, contrary to the usual superconducting-normal metal-superconducting junctions, the suppression of the supercurrent in the superconducting-helical metal-superconducting junction is mainly due to fluctuations of impurities in the junctions. Our results, which are a condensed matter realization of a part of the Mikheyev-Smirnov-Wolfenstein effect for neutrinos, show that the relationship between normal state conductance and the critical current of Josephson junctions is significantly modified for Josephson junctions on the surface of topological insulators. We also study the temperature dependence of the supercurrent and present a two fluid model which can explain some of the recent experimental results in Josephson junctions on the edge of topological insulators. PMID- 26849611 TI - Field-Induced Lifshitz Transition without Metamagnetism in CeIrIn(5). AB - We report high magnetic field measurements of magnetic torque, thermoelectric power, magnetization, and the de Haas-van Alphen effect in CeIrIn_{5} across 28 T, where a metamagnetic transition was suggested in previous studies. The thermoelectric power displays two maxima at 28 and 32 T. Above 28 T, a new, low de Haas-van Alphen frequency with a strongly enhanced effective mass emerges, while the highest frequency observed at low field disappears entirely. This suggests a field-induced Lifshitz transition. However, longitudinal magnetization does not show any anomaly up to 33 T, thus ruling out a metamagnetic transition at 28 T. PMID- 26849610 TI - Orbital Glass State of the Nearly Metallic Spinel Cobalt Vanadate. AB - Strain, magnetization, dielectric relaxation, and unpolarized and polarized neutron diffraction measurements were performed to study the magnetic and structural properties of spinel Co_{1-x}V_{2+x}O_{4}. The strain measurement indicates that, upon cooling, DeltaL/L in the order of ~10^{-4} starts increasing below T_{C}, becomes maximum at T_{max}, and then decreases and changes its sign at T^{*}. Neutron measurements indicate that a collinear ferrimagnetic order develops below T_{C} and upon further cooling noncollinear ferrimagnetic ordering occurs below T_{max}. At low temperatures, the dielectric constant exhibits a frequency dependence, indicating slow dynamics. These results indicate the existence of an orbital glassy state at low temperatures in this nearly metallic frustrated magnet. PMID- 26849612 TI - Quantum Stoner-Wohlfarth Model. AB - The quantum mechanical counterpart of the famous Stoner-Wohlfarth model-an easy axis magnet in a tilted magnetic field-is studied theoretically and through simulations as a function of the spin size S in a sweeping longitudinal field. Beyond the classical Stoner-Wohlfarth transition, the sweeping field-induced adiabatic change of states slows down as S increases, leading to a dynamical quantum phase transition. This result gives us new insights to describe the collapse of the metastability from the viewpoint of a critical phenomenon associated with the Landau-Zener tunneling gaps. Furthermore, a beating of the amplitude of the magnetization (the spin-length fidelity) is discovered after the Stoner-Wohlfarth transition. The period of the beating, confirmed analytically, arises from a new type of quantum phase factor. PMID- 26849613 TI - Long-Range Plasmon-Assisted Energy Transfer between Fluorescent Emitters. AB - We demonstrate plasmon-assisted energy transfer between fluorophores located at distances up to 7 MUm on the top of a thin silver film. Thanks to the strong confinement and large propagation length of surface plasmon polaritons, the range of the energy transfer is almost 2 orders of magnitude larger than the values reported in the literature so far. The parameters driving the energy transfer range are thoroughly characterized and are in very good agreement with theoretically expected values. PMID- 26849614 TI - Electronic Enhancement of the Exciton Coherence Time in Charged Quantum Dots. AB - Minimizing decoherence due to coupling of a quantum system to its fluctuating environment is at the forefront of quantum information and photonics research. Nature sets the ultimate limit, however, given by the strength of the system's coupling to the electromagnetic field. Here, we establish the ability to electronically control this coupling and enhance the optical coherence time of the charged exciton transition in quantum dots embedded in a photonic waveguide. By manipulating the electronic wave functions through an applied lateral electric field, we increase the coherence time from ~1.4 to ~2.7 ns. Numerical calculations reveal that longer coherence arises from the separation of charge carriers by up to ~6 nm, which leads to a 30% weaker transition dipole moment. The ability to electronically control the coherence time opens new avenues for quantum communication and novel coupling schemes between distant qubits. PMID- 26849615 TI - Hamiltonian Dynamics of Protein Filament Formation. AB - We establish the Hamiltonian structure of the rate equations describing the formation of protein filaments. We then show that this formalism provides a unified view of the behavior of a range of biological self-assembling systems as diverse as actin, prions, and amyloidogenic polypeptides. We further demonstrate that the time-translation symmetry of the resulting Hamiltonian leads to previously unsuggested conservation laws that connect the number and mass concentrations of fibrils and allow linear growth phenomena to be equated with autocatalytic growth processes. We finally show how these results reveal simple rate laws that provide the basis for interpreting experimental data in terms of specific mechanisms controlling the proliferation of fibrils. PMID- 26849616 TI - Motility of Colonial Choanoflagellates and the Statistics of Aggregate Random Walkers. AB - We illuminate the nature of the three-dimensional random walks of microorganisms composed of individual organisms adhered together. Such aggregate random walkers are typified by choanoflagellates, eukaryotes that are the closest living relatives of animals. In the colony-forming species Salpingoeca rosetta we show that the beating of each flagellum is stochastic and uncorrelated with others, and the vectorial sum of the flagellar propulsion manifests as stochastic helical swimming. A quantitative theory for these results is presented and species variability discussed. PMID- 26849617 TI - Colloidal Swarms Can Settle Faster than Isolated Particles: Enhanced Sedimentation near Phase Separation. AB - By experimenting on model colloids where depletion forces can be carefully tuned and quantified, we show that attractive interactions consistently "promote" particle settling, so much that the sedimentation velocity of a moderately concentrated dispersion can even exceed its single-particle value. At larger particle volume fraction phi, however, hydrodynamic hindrance eventually takes over. Hence, v(phi) actually displays a nonmonotonic trend that may threaten the stability of the settling front to thermal perturbations. Finally, by discussing a representative case, we show that these results are relevant to the investigation of protein association effects by ultracentrifugation. PMID- 26849619 TI - Geometric Frustration of Colloidal Dimers on a Honeycomb Magnetic Lattice. AB - We study the phase behavior and the collective dynamics of interacting paramagnetic colloids assembled above a honeycomb lattice of triangular shaped magnetic minima. A frustrated colloidal molecular crystal is realized when filling these potential minima with exactly two particles per pinning site. External in-plane rotating fields are used to anneal the system into different phases, including long range ordered stripes, random fully packed loops, labyrinth and disordered states. At a higher amplitude of the annealing field, the dimer lattice displays a two-step melting transition where the initially immobile dimers perform first localized rotations and later break up by exchanging particles across consecutive lattice minima. PMID- 26849618 TI - Unexpected Molecular Weight Effect in Polymer Nanocomposites. AB - The properties of the interfacial layer between the polymer matrix and nanoparticles largely determine the macroscopic properties of polymer nanocomposites (PNCs). Although the static thickness of the interfacial layer was found to increase with the molecular weight (MW), the influence of MW on segmental relaxation and the glass transition in this layer remains to be explored. In this Letter, we show an unexpected MW dependence of the interfacial properties in PNC with attractive polymer-nanoparticle interactions: the thickness of the interfacial layer with hindered segmental relaxation decreases as MW increases, in sharp contrast to theoretical predictions. Further analyses reveal a reduction in mass density of the interfacial layer with increasing MW, which can elucidate these unexpected dynamic effects. Our observations call for a significant revision of the current understandings of PNCs and suggest interesting ways to tailor their properties. PMID- 26849620 TI - Heterogeneous Preference and Local Nonlinearity in Consensus Decision Making. AB - In recent years, a large body of research has focused on unveiling the fundamental physical processes that living systems utilize to perform functions, such as coordinated action and collective decision making. Here, we demonstrate that important features of collective decision making among higher organisms are captured effectively by a novel formulation of well-characterized physical spin systems, where the spin state is equivalent to two opposing preferences, and a bias in the preferred state represents the strength of individual opinions. We reveal that individuals (spins) without a preference (unbiased or uninformed) play a central role in collective decision making, both in maximizing the ability of the system to achieve consensus (via enhancement of the propagation of spin states) and in minimizing the time taken to do so (via a process reminiscent of stochastic resonance). Which state (option) is selected collectively, however, is shown to depend strongly on the nonlinearity of local interactions. Relatively linear social response results in unbiased individuals reinforcing the majority preference, even in the face of a strongly biased numerical minority (thus promoting democratic outcomes). If interactions are highly nonlinear, however, unbiased individuals exert the opposite influence, promoting a strongly biased minority and inhibiting majority preference. These results enhance our understanding of physical computation in biological collectives and suggest new avenues to explore in the collective dynamics of spin systems. PMID- 26849621 TI - Screening of PAX6 gene in Italian congenital aniridia patients revealed four novel mutations. AB - PURPOSE: To uncover underlying mutations in a cohort of Italian patients with aniridia, a rare congenital panocular condition with an incidence ranging from 1:64,000 to 1:100,000. The disease may be found isolated or in association with other syndromes characterized by partial or complete absence of the iris and iris hypoplasia. METHODS: We analyzed the PAX6 gene in 11 patients with aniridia fulfilling the following inclusion criteria: partial or complete absence of the iris and age < 18 years at the time of diagnosis. DNA sequence analysis was integrated with Multiple Ligation Probe Assay (MLPA) analysis. RESULTS: We identified seven PAX6 mutations, including four novel ones. The majority of mutations lie in the DNA-binding domain and all produce a truncated protein. All tested patients did not have WT1 gene deletions thus excluding the WAGR syndrome. We present the clinical findings in the four cases harboring novel mutations. We were unable to identify mutations in four cases with complete aniridia thus indicating that other gene/s could be involved in the disease. CONCLUSIONS: It is important to establish the molecular diagnosis early to avoid repeated and long term screening for Wilms tumor. Our work further emphasizes that a wide range of ocular phenotypes are associated with loss of function PAX6 mutations. In addition to the possibility of stochastic variations, other genetic variations could play a role as modifier genes, thus giving rise to the observed different ocular phenotypes. PMID- 26849622 TI - Insulin Increases Expression of TRPC6 Channels in Podocytes by a Calcineurin Dependent Pathway. AB - BACKGROUND/AIMS: Insulin signaling to podocytes is relevant for the function of the glomerulus. Now, we tested the hypothesis that insulin increases the surface expression of canonical transient receptor potential canonical type 6 (TRPC6) channels in podocytes by a calcineurin-dependent pathway. METHODS: We used quantitative RT-PCR, immunoblotting, immunofluorescence and fluorescence spectrophotometry in cultured podocytes. Activation of Nuclear Factor of Activated T-cells (NFATc1) was measured using a specific calorimetric assay. RESULTS: Insulin increased the expression of TRPC6 transcripts and protein in podocytes. Insulin increased TRPC6 transcripts in a time and dose-dependent manner. The insulin-induced elevation of TRPC6 transcripts was blocked in the presence of tacrolimus, cyclosporine A, and NFAT-inhibitor (each p < 0.01 by ANOVA and Bonferroni's multiple comparison test). Transcripts of NOX4, another target gene of the calcineurin-NFAT pathway, were affected in a similar way. Immunoblotting showed that the administration of 100 nmol/L insulin increased TRPC6-proteins 2-fold within 48 hours. Insulin increased the activity of NFATc1 in nuclear extracts (p < 0.001) whereas tacrolimus, cyclosporine A, and NFAT inhibitor blocked that insulin effect (p < 0.001; two way ANOVA). Immunofluorescence showed that insulin increased TRPC6-expression on the cell surface. Fluorescence-spectrophotometry and manganese quench experiments indicated that the increased TRPC6-expression after insulin administration was accompanied by an elevated transplasmamembrane cation influx. Insulin-stimulated surface expression of TRPC6 as well as transplasmamembrane cation influx could be reduced by pretreatment with tacrolimus. CONCLUSION: Insulin increases the expression of TRPC6 channels in podocytes by activation of the calcineurin dependent pathway. PMID- 26849623 TI - The Antitumor Effect of DYC-279 on Human Hepatocellular Carcinoma HepG2 Cells. AB - DYC-279 is a newly synthesized compound. In this study, we revealed that DYC-279 could inhibit the proliferation of HepG2 cells in a dose- and time-dependent manner using the CCK-8 test. FACS showed that DYC-279 induced a G2/M arrest and apoptosis in a dose-dependent manner. Western blot demonstrated that DYC-279 induced G2/M arrest effect was correlated with the inhibition of cyclin-dependent kinase 1 activity, including a concomitant downregulation of cyclinD1 and cdc2 and upregulation of cyclinB1 in HepG2 cells. DYC-279 also significantly increased the ratio of Bax/Bcl-2, and stimulated the released of cytochrome c into cytosol and also activated caspase-9 and caspase-3, suggesting DYC-279 induced apoptosis via mitochondrial apoptotic pathway. These data support that DYC-279 has anticancer properties in HepG2 cells and may be used as a novel effective reagent in the treatment of human liver cancer. PMID- 26849624 TI - Pre-treatment with oral hydroxyurea prior to intensive chemotherapy improves early survival of patients with high hyperleukocytosis in acute myeloid leukemia. AB - Acute myeloid leukemia with high white blood cell count (WBC) is a medical emergency. A reduction of tumor burden with hydroxyurea may prevent life threatening complications induced by straight chemotherapy. To evaluate this strategy, we reviewed medical charts of adult patients admitted to our institution from 1997 to 2011 with non-promyelocytic AML and WBC over 50 G/L. One hundred and sixty patients were included with a median WBC of 120 G/L (range 50 450), 107 patients received hydroxyurea prior to chemotherapy, and 53 received emergency induction chemotherapy (CT). Hospital mortality was lower for patients treated with hydroxyurea (34% versus 19%, p = 0.047) even after adjusting for age (p < 0.01) and initial WBC count (p = 0.02). No evidence of any difference between treatment groups in terms of WBC decline kinetics and disease free survival (p = 0.87) was found. Oral hydroxyurea prior to chemotherapy seems a safe and efficient strategy to reduce early death of hyperleukocytic AML patients. PMID- 26849625 TI - Beneficial Effects of Norepinephrine Alone on Cardiovascular Function and Tissue Oxygenation in a Pig Model of Cardiogenic Shock. AB - INTRODUCTION: The present study was developed to investigate the effects of norepinephrine alone on hemodynamics and intrinsic cardiac function in a pig model of cardiogenic shock mimicking the clinical setting. METHODS: Cardiogenic shock was induced by 1-h ligation of the left anterior descending (LAD) artery followed by reperfusion. Pigs were monitored with a Swan-Ganz catheter, a transpulmonary thermodilution catheter, and a conductance catheter placed in the left ventricle for pressure-loop measurements. Measurements were performed before LAD occlusion, 1 h after LAD occlusion, and 4 h after myocardial reperfusion. RESULTS: Myocardial infarction and reperfusion was followed by cardiogenic shock characterized by a significant increase in heart rate and significant decreases in mean arterial pressure (MAP), mixed venous oxygen saturation (SVO2), left ventricular end-diastolic pressure (LVEDP), prerecruitable stroke work (PRSW), and cardiac power index (CPI). Lactate levels were significantly increased. The systemic vascular resistance index (SVRI) and global end-diastolic volume index (GEDVI) remained unchanged. When compared with the control group (n = 6), norepinephrine infusion (n = 6) was associated with no changes in heart rate, a significant increase in MAP, SVO2, left ventricular ejection fraction, pressure development during isovolumic contraction, SVRI, and CPI and a decrease in lactate level. Cardiac index tended to increase (P = 0.059), whereas PRSW did not change in the norepinephrine group. LVEDP and GEDVI remained unchanged. CONCLUSIONS: Norepinephrine alone is able to improve hemodynamics, cardiac function, and tissue oxygenation in a pig model of ischemic cardiogenic shock. PMID- 26849626 TI - The Utility of Inflammatory and Endothelial Markers to Identify Infection in Emergency Department Patients. PMID- 26849627 TI - Biomarkers or Clinical Observations to Identify (Outcome of) Emergency Department Patients With Infection? PMID- 26849629 TI - 17beta-Estradiol Accelerated Renal Tubule Regeneration in Male Rats After Ischemia/Reperfusion-Induced Acute Kidney Injury. AB - Ischemic/reperfusion injury (IRI) is the most common cause of acute kidney injury (AKI). Murine studies report that pretreatment with 17beta-estradiol protects against AKI using multiple mechanisms, but how 17beta-estradiol is involved in regenerating tubular cells is unknown. To visualize the kidney injury and repair, we used 17beta-estradiol to treat rats with postischemic acute kidney injury. AKI was induced by clamping the renal pedicle for 90 minutes 2 weeks after a unilateral nephrectomy. Rats were treated with an intravenous injection of 17beta estradiol or vehicle immediately after reperfusion. Kidney injury was assessed by measuring biochemical and histopathological changes. Immunohistochemical staining of vimentin, proliferating cell nuclear antigen (PCNA), and E-cadherin were used to assess dedifferentiation, proliferation, and redifferentiation. Rats treated with 17beta-estradiol had less kidney injury than did vehicle-treated rats post IRI day 1. The number of PCNA-positive (PCNA) cells was significantly higher in post-IRI kidneys on day 1 in 17beta-estradiol-treated rats. Moreover, vimentin and E-cadherin cells, which were interpreted as regeneration markers, were expressed earlier and significantly more copiously in 17beta-estradiol-treated rats. We hypothesize that 17beta-estradiol attenuates IRI-induced AKI by reducing inflammation and accelerating injured tubular cell regeneration. PMID- 26849628 TI - Surfactant Proteins SP-A and SP-D Ameliorate Pneumonia Severity and Intestinal Injury in a Murine Model of Staphylococcus Aureus Pneumonia. AB - Staphylococcus aureus pneumonia is an important cause of sepsis which causes gut injury, inflammation, and apoptosis. The surfactant proteins surfactant protein A (SP-A) and surfactant protein D (SP-D) bind bacterial pathogens and facilitate clearance of pathogens, apoptotic bodies, and modulate immune responses. SP-A and SP-D are expressed in both lung and gut epithelia. We hypothesize SP-A and SP-D regulate pneumonia severity and gut injury during pneumonia. METHODS: Wild-type (WT) and SP-A and SP-D double knockout (SP-A/D KO) mice were subjected to S. aureus or sham pneumonia. Bronchoalveolar lavage and tissue harvest were performed 24 h later. Pneumonia severity, gut mucosal injury, inflammation, and apoptosis were measured using a combination of histology, immunohistochemistry, cytokine assay, TUNEL assay, quantitative real-time polymerase chain reaction, and Western blot analyses. RESULTS: Pneumonia increased gut inflammation, apoptosis, and mucosal injury in both groups. Pneumonia histology and bacterial growth in bronchoalveolar lavage fluid demonstrate more severe infection in SP A/D KO mice compared with WT controls. SP-A/D KO mice with pneumonia also demonstrate more severe histologic gut mucosal injury, increased gut apoptosis, elevated caspase-3 levels, and Bax/Bcl-2 mRNA expression compared with WT pneumonia mice. Nuclear factor kappaB (NF-kappaB) p65 expression and its nuclear translocation, gut levels of tumor necrosis factor alpha and interleukin-1beta were all increased in SP-A/D KO mice with pneumonia compared with WT controls. CONCLUSIONS: These data provide evidence SP-A and SP-D attenuate S. aureus pneumonia severity resulting in decreased intestinal mucosal injury, apoptosis, and inflammation. Improved pulmonary clearance of S. aureus decreased caspase-3 and Bax/Bcl-2 expressions and decreased activation of the NF-kappaB signaling pathway in intestine represent potential mechanisms for the effects of SP-A and SP-D on gut injury during pneumonia. PMID- 26849630 TI - Enhanced Efficacy of Combinations of Pexiganan with Colistin Versus Acinetobacter Baumannii in Experimental Sepsis. AB - We investigated the efficacy of colistin combined with pexiganan in experimental mouse models of Acinetobacter baumannii infection.Adult male BALB/c mice received intraperitoneally 1 mL saline containing 2 * 10 CFU of susceptible and multiresistant A. baumannii. Two hours after bacterial challenge, animals received 1 mg/kg of colistin, 1 mg/kg of pexiganan, or 1 mg/kg of colistin plus 1 mg/kg of pexiganan.Blood culture positivity, the quantities of bacteria in the intra-abdominal fluid, the rate of lethality and immunological studies, such as immunophenotyping and NK cytotoxicity, were evaluated.In the in vitro study, A. baumannii showed susceptibility to colistin and pexiganan and a strong synergy was observed by testing colistin combined with pexiganan with fractionary inhibitory concentration index of 0.312 for both strains.In the in vivo study colistin or pexiganan alone showed a good antimicrobial efficacy. When colistin was combined with pexiganan, the positive interaction produced low bacterial counts that were statistically significant versus singly treated groups. For both strains the highest rate of survival was observed in combined-treated groups (90%).Pexiganan increased NK cytotoxic activity over the levels of infected and colistin-treated animals.In conclusion, pexiganan combined with colistin was found to be efficacious against A. baumannii infection. PMID- 26849631 TI - Association of Urinary Neutrophil Gelatinase-Associated Lipocalin With Long-Term Renal Outcomes in ICU Survivors: A Retrospective Observational Cohort Study. AB - BACKGROUND: Epidemiological studies recently suggested that acute kidney injury (AKI) in intensive care units (ICUs) increases the risk of chronic kidney disease development and progression. However, whether any AKI biomarker can predict long term renal outcomes in ICU survivors remains unclear. This study was undertaken to elucidate the role of urinary biomarkers for long-term renal outcome prediction after ICU discharge. METHODS: This retrospective observational study examined 495 adult patients who had been admitted to the ICU of the University of Tokyo Hospital. Major adverse kidney events (MAKE): death, incident end-stage renal disease (ESRD), and halving of estimated glomerular filtration rate (eGFR), at hospital discharge and long-term renal outcomes of 30% reduction of eGFR or incident ESRD were evaluated. RESULTS: Among all the enrolled 495 patients, 393 patients were discharged from the hospital without MAKE. Data of eGFR up to two years after ICU discharge were available for 173 patients; 63 patients (36.4%) were positive for long-term renal outcomes. Step-wise logistic regression analysis demonstrated that male sex and urinary neutrophil gelatinase-associated lipocalin (NGAL) measured at ICU admission showed significant associations with long-term renal outcomes. Receiver operating characteristic curve analysis showed the area under the curve of 0.66 (95% confidence interval 0.57-0.74) for prediction of long-term renal outcome by urinary NGAL. CONCLUSION: Urinary NGAL measured at ICU admission was significantly associated with long-term renal outcomes after hospital discharge in MAKE-free ICU survivors. Urinary NGAL measurements at ICU might be useful to identify a high risk population of kidney disease progression after intensive care. PMID- 26849632 TI - Hydrogen Inhalation is Superior to Mild Hypothermia in Improving Cardiac Function and Neurological Outcome in an Asphyxial Cardiac Arrest Model of Rats. AB - BACKGROUND: Non-shockable rhythms represent an increasing proportion of reported cases of out-of-hospital cardiac arrest but with an associated poor prognosis. In the present study, we investigated the effects of hydrogen inhalation on cardiac and neurological function after cardiopulmonary resuscitation and compared the therapeutic benefit with hypothermia in an asphyxial rat model of cardiac arrest. METHODS: Cardiopulmonary resuscitation was initiated after 5 min of untreated asphyxial cardiac arrest. Animals were randomly assigned to three experimental groups immediately after successful resuscitation: ventilation with 2% hydrogen/98% oxygen under normothermia (H2 inhalation), ventilation with 2% nitrogen/98% oxygen under normothermia (Control), and ventilation with 2% nitrogen/98% oxygen under hypothermia (TH). Mixed gas inhalation continued for 1 h while hypothermia continued for 2 h. Animals were observed up to 96 h for assessment of survival and neurologic recovery. RESULTS: No statistical differences in baseline measurements were observed among groups and all the animals were successfully resuscitated. Serum cardiac troponin T and S100B measured during earlier post-resuscitation period were markedly reduced in both H2 inhalation and hypothermic groups. However, significantly better left ventricular ejection fraction, cardiac work, and neurological deficit score were observed in the H2 inhalation group. Ninety-six hours survival rate was significantly higher in the H2 inhalation group (75.0%), either compared with TH (45.8%) or compared with Control (33.3%). But there was no statistical difference between TH and Control. CONCLUSIONS: Small amounts of inhaled hydrogen were superior to mild hypothermia in improving cardiac function and neurological outcome in this asphyxial rat model of cardiac arrest. PMID- 26849633 TI - Recent developments in severe sepsis research: from bench to bedside and back. AB - Severe sepsis remains a worldwide threat, not only in industrialized countries, due to their aging population, but also in developing countries where there still are numerous cases of neonatal and puerperal sepsis. Tools for early diagnosis, a prerequisite for rapid and appropriate antibiotic therapy, are still required. In this review, we highlight some recent developments in our understanding of the associated systemic inflammatory response that help deciphering pathophysiology (e.g., epigenetic, miRNA, regulatory loops, compartmentalization, apoptosis and synergy) and discuss some of the consequences of sepsis (e.g., immune status, neurological and muscular alterations). We also emphasize the challenge to better define animal models and discuss past failures in clinical investigations in order to define new efficient therapies. PMID- 26849635 TI - Peter Kramp: 1941-2015. PMID- 26849634 TI - Ex-armed forces personnel in prison: Where do we stand? PMID- 26849636 TI - The Frequency of AVN Following Reconstructive Hip Surgery in Children With Cerebral Palsy: A Systematic Review. AB - BACKGROUND: Children with cerebral palsy (CP) undergoing reconstructive hip surgery are at risk for developing avascular necrosis (AVN). The purpose of this systematic review was to investigate the reported frequency of AVN, the amount and quality of literature available, and possibly identity risk factors for developing AVN following reconstructive surgery for hip displacement in children with CP. METHODS: We performed a review of the literature using EMBASE and MEDLINE databases. Studies investigating the outcome of reconstructive hip surgery in patients with CP that identified the presence or absence of AVN were included. Study quality was assessed using the Methodological Index for Non Randomized Studies and the Oxford Centre for Evidence-Based Medicine scale. RESULTS: Three hundred and ninety-nine articles were identified using our search strategy. Twenty-nine studies were included for data extraction after full-text review. The frequency of AVN ranged from 0% to 46% with an overall rate across studies of 7.5%. Presence of AVN was the primary outcome in 2 studies. The frequency of AVN in these studies was significantly higher than other studies at 37% and 46%. No statistically significant associations were found between age at surgery, severity of hip subluxation, length of follow-up, or type of surgery (combined varus derotation osteotomy and pelvic osteotomy vs. varus derotation osteotomy alone), and the rate of AVN. The majority of studies did not comment on methods used for determining diagnosis or severity of AVN and clinical significance was not well documented. CONCLUSIONS: Children with CP undergoing reconstructive hip surgery are at risk of developing AVN. Frequency and severity of this complication is poorly documented in the literature. On the basis of current evidence no significant risk factors were identified; however, it is not possible to draw firm conclusions about them. Incidence of AVN was higher in studies in which AVN was a primary outcome suggesting that the true frequency of AVN may be higher than is currently understood. PMID- 26849637 TI - Antitumor activity of alectinib, a selective ALK inhibitor, in an ALK-positive NSCLC cell line harboring G1269A mutation: Efficacy of alectinib against ALK G1269A mutated cells. AB - PURPOSE: Alectinib is a highly selective next-generation anaplastic lymphoma kinase (ALK) inhibitor. Although alectinib shows inhibitory activity against various crizotinib-resistant ALK mutations in studies using cell-free kinase assays and Ba/F3 cell-based assays, it has not been tested for efficacy against non-small cell lung cancer (NSCLC) with the ALK mutations. METHODS: We conducted in vitro and in vivo investigations into the antitumor activity of alectinib against an ALK-positive NSCLC cell line, SNU-2535, which harbors an ALK G1269A mutation. The clinical efficacy of alectinib against a NSCLC patient harboring ALK G1269A mutation was evaluated in the phase I part of the North American study. RESULTS: Alectinib exhibited antiproliferative activity against SNU-2535 cells in vitro with IC50 of 33.1 nM. Alectinib strongly inhibited phosphorylation of ALK and its downstream signaling molecules ERK1/2, AKT, and STAT3. In a mouse xenograft model, once-daily oral administration of alectinib for 21 days resulted in strong tumor regression. In addition, administration of alectinib for 100 days achieved continuous tumor regression without tumor regrowth in all mice. Notably, eradication of tumor cells was observed in half of the mice. In the clinical study, a patient with ALK G1269A mutation showed partial response to alectinib with a duration of response of 84 days. CONCLUSION: These results indicated that alectinib has potent antitumor activity against NSCLC cells harboring the crizotinib-resistant mutation ALK G1269A. It is expected that alectinib would provide a valuable therapeutic option for patients with NSCLC having not only native ALK but also crizotinib-resistant ALK mutations. PMID- 26849638 TI - Problematic Internet use was more common in Turkish adolescents with major depressive disorders than controls. AB - AIM: This study compared problematic Internet use (PIU) rates in 12- to 18-year olds with major depressive disorder (MDD) and healthy controls and explored potential links between PIU and suicide among patients with MDD. METHODS: The study sample consisted of 120 patients with MDD (62.5% girls) and 100 controls (58% girls) with a mean age of 15. Suicide ideation and suicide attempts were evaluated, and sociodemographic data were collected. In addition, the Children's Depression Inventory, Young Internet Addiction Test and Suicide Probability Scale were applied. RESULTS: The results showed that PIU rates were significantly higher in the MDD cases than the controls (p < 0.001). The analysis of covariance results showed that there was no relationship between potential suicide and the Young Internet Addiction Test score in MDD cases. However, the hopelessness subscale scores of the MDD patients with PIU were significantly higher than the scores of those without PIU. CONCLUSION: Our results show that PIU was higher in adolescents with MDD and hopelessness was more prevalent among MDD patients with PIU, but no links with potential suicide were found. As this study was a cross sectional one, it did not allow us to infer a causality relationship between PIU and MDD. PMID- 26849639 TI - Commentary: "Randomize, Then Consent" or "Consent, Then Randomize"?: Revitalizing the Issue of Preconsent Randomization. PMID- 26849640 TI - Re: Thyroid Cancer Among Young People in Fukushima. PMID- 26849641 TI - Soluble Adhesion Molecules in Patients Coinfected with HIV and HCV: A Predictor of Outcome. AB - BACKGROUND: Higher serum levels of adhesion molecules (sICAM-1 and sVCAM-1) are associated with advanced liver fibrosis in patients coinfected with human immunodeficiency virus and hepatitis C virus. We assessed the relationship between serum levels of adhesion molecules and liver-related events (LRE) or death, in coinfected patients. METHODS: We studied clinical characteristics and outcomes of 182 coinfected patients with a baseline liver biopsy (58 with advanced fibrosis) and simultaneous plasma samples who were followed for median of 9 years. We used receiver-operating characteristic (ROC) curves to calculate optimized cutoff values (OCV) of sICAM-1 and sVCAM-1, defined as the values with the highest combination of sensitivity and specificity for LRE. We used multivariate regression analysis to test the association between OCVs of sICAM-1 and sVCAM-1 and outcomes. The variables for adjustment were age, HIV transmission category, liver fibrosis, baseline CD4+ T-cell counts, antiretroviral therapy, and sustained virologic response (SVR). RESULTS: During the study period 51 patients had SVR, 19 had LRE, and 16 died. The OCVs for LRE were 5.68 Log pg/mL for sICAM-1 and 6.25 Log pg/mL for sVCAM-1, respectively. The adjusted subhazard ratio (aSHR) (95% confidence interval [CI]) of death or LRE, whichever occurred first, for sICAM-1 and sVCAM-1 > OCV were 3.98 ([1.14; 13.89], P = 0.030) and 2.81 ([1.10; 7.19], respectively (P = 0.030). CONCLUSIONS: Serum levels of sICAM 1 and sVCAM-1 can serve as markers of outcome in HIV/HCV-coinfected patients. Therapies targeting necroinflammatory damage and fibrogenesis may have a role in the management chronic hepatitis C. PMID- 26849642 TI - Ungulate Reproductive Parameters Track Satellite Observations of Plant Phenology across Latitude and Climatological Regimes. AB - The effect of climatically-driven plant phenology on mammalian reproduction is one key to predicting species-specific demographic responses to climate change. Large ungulates face their greatest energetic demands from the later stages of pregnancy through weaning, and so in seasonal environments parturition dates should match periods of high primary productivity. Interannual variation in weather influences the quality and timing of forage availability, which can influence neonatal survival. Here, we evaluated macro-scale patterns in reproductive performance of a widely distributed ungulate (mule deer, Odocoileus hemionus) across contrasting climatological regimes using satellite-derived indices of primary productivity and plant phenology over eight degrees of latitude (890 km) in the American Southwest. The dataset comprised > 180,000 animal observations taken from 54 populations over eight years (2004-2011). Regionally, both the start and peak of growing season ("Start" and "Peak", respectively) are negatively and significantly correlated with latitude, an unusual pattern stemming from a change in the dominance of spring snowmelt in the north to the influence of the North American Monsoon in the south. Corresponding to the timing and variation in both the Start and Peak, mule deer reproduction was latest, lowest, and most variable at lower latitudes where plant phenology is timed to the onset of monsoonal moisture. Parturition dates closely tracked the growing season across space, lagging behind the Start and preceding the Peak by 27 and 23 days, respectively. Mean juvenile production increased, and variation decreased, with increasing latitude. Temporally, juvenile production was best predicted by primary productivity during summer, which encompassed late pregnancy, parturition, and early lactation. Our findings offer a parsimonious explanation of two key reproductive parameters in ungulate demography, timing of parturition and mean annual production, across latitude and changing climatological regimes. Practically, this demonstrates the potential for broad scale modeling of couplings between climate, plant phenology, and animal populations using space-borne observations. PMID- 26849644 TI - Estimation of the Basic Reproductive Number and Mean Serial Interval of a Novel Pathogen in a Small, Well-Observed Discrete Population. AB - BACKGROUND: Accurately assessing the transmissibility and serial interval of a novel human pathogen is public health priority so that the timing and required strength of interventions may be determined. Recent theoretical work has focused on making best use of data from the initial exponential phase of growth of incidence in large populations. METHODS: We measured generational transmissibility by the basic reproductive number R0 and the serial interval by its mean Tg. First, we constructed a simulation algorithm for case data arising from a small population of known size with R0 and Tg also known. We then developed an inferential model for the likelihood of these case data as a function of R0 and Tg. The model was designed to capture a) any signal of the serial interval distribution in the initial stochastic phase b) the growth rate of the exponential phase and c) the unique combination of R0 and Tg that generates a specific shape of peak incidence when the susceptible portion of a small population is depleted. FINDINGS: Extensive repeat simulation and parameter estimation revealed no bias in univariate estimates of either R0 and Tg. We were also able to simultaneously estimate both R0 and Tg. However, accurate final estimates could be obtained only much later in the outbreak. In particular, estimates of Tg were considerably less accurate in the bivariate case until the peak of incidence had passed. CONCLUSIONS: The basic reproductive number and mean serial interval can be estimated simultaneously in real time during an outbreak of an emerging pathogen. Repeated application of these methods to small scale outbreaks at the start of an epidemic would permit accurate estimates of key parameters. PMID- 26849643 TI - A New Computational Model for Neuro-Glio-Vascular Coupling: Astrocyte Activation Can Explain Cerebral Blood Flow Nonlinear Response to Interictal Events. AB - Developing a clear understanding of the relationship between cerebral blood flow (CBF) response and neuronal activity is of significant importance because CBF increase is essential to the health of neurons, for instance through oxygen supply. This relationship can be investigated by analyzing multimodal (fMRI, PET, laser Doppler...) recordings. However, the important number of intermediate (non observable) variables involved in the underlying neurovascular coupling makes the discovery of mechanisms all the more difficult from the sole multimodal data. We present a new computational model developed at the population scale (voxel) with physiologically relevant but simple equations to facilitate the interpretation of regional multimodal recordings. This model links neuronal activity to regional CBF dynamics through neuro-glio-vascular coupling. This coupling involves a population of glial cells called astrocytes via their role in neurotransmitter (glutamate and GABA) recycling and their impact on neighboring vessels. In epilepsy, neuronal networks generate epileptiform discharges, leading to variations in astrocytic and CBF dynamics. In this study, we took advantage of these large variations in neuronal activity magnitude to test the capacity of our model to reproduce experimental data. We compared simulations from our model with isolated epileptiform events, which were obtained in vivo by simultaneous local field potential and laser Doppler recordings in rats after local bicuculline injection. We showed a predominant neuronal contribution for low level discharges and a significant astrocytic contribution for higher level discharges. Besides, neuronal contribution to CBF was linear while astrocytic contribution was nonlinear. Results thus indicate that the relationship between neuronal activity and CBF magnitudes can be nonlinear for isolated events and that this nonlinearity is due to astrocytic activity, highlighting the importance of astrocytes in the interpretation of regional recordings. PMID- 26849645 TI - Molecular and Cellular Profiling of Scalp Psoriasis Reveals Differences and Similarities Compared to Skin Psoriasis. AB - Scalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis in other skin areas. We sought to determine the cellular and molecular phenotype of scalp psoriasis by performing a comparative analysis of scalp and skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement and 10 control subjects without psoriasis. Our results suggest that even in the scalp, psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprint were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with that of skin psoriasis, which was mainly associated with activation of TNFalpha/L 17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes. PMID- 26849646 TI - Performance Feedback Processing Is Positively Biased As Predicted by Attribution Theory. AB - A considerable literature on attribution theory has shown that healthy individuals exhibit a positivity bias when inferring the causes of evaluative feedback on their performance. They tend to attribute positive feedback internally (e.g., to their own abilities) but negative feedback externally (e.g., to environmental factors). However, all empirical demonstrations of this bias suffer from at least one of the three following drawbacks: First, participants directly judge explicit causes for their performance. Second, participants have to imagine events instead of experiencing them. Third, participants assess their performance only after receiving feedback and thus differences in baseline assessments cannot be excluded. It is therefore unclear whether the classically reported positivity bias generalizes to setups without these drawbacks. Here, we aimed at establishing the relevance of attributions for decision-making by showing an attribution-related positivity bias in a decision-making task. We developed a novel task, which allowed us to test how participants changed their evaluations in response to positive and negative feedback about performance. Specifically, we used videos of actors expressing different facial emotional expressions. Participants were first asked to evaluate the actors' credibility in expressing a particular emotion. After this initial rating, participants performed an emotion recognition task and did--or did not--receive feedback on their veridical performance. Finally, participants re-rated the actors' credibility, which provided a measure of how they changed their evaluations after feedback. Attribution theory predicts that participants change their evaluations of the actors' credibility toward the positive after receiving positive performance feedback and toward the negative after negative performance feedback. Our results were in line with this prediction. A control condition without feedback showed that correct or incorrect performance alone could not explain the observed positivity bias. Furthermore, participants' behavior in our task was linked to the most widely used measure of attribution style. In sum, our findings suggest that positive and negative performance feedback influences the evaluation of task-related stimuli, as predicted by attribution theory. Therefore, our study points to the relevance of attribution theory for feedback processing in decision making and provides a novel outlook for decision-making biases. PMID- 26849647 TI - Correction: Multiple Pathogens Including Potential New Species in Tick Vectors in Cote d'Ivoire. PMID- 26849648 TI - Ecophenotypic Variation and Developmental Instability in the Late Cretaceous Echinoid Micraster brevis (Irregularia; Spatangoida). AB - The Late Cretaceous echinoid genus Micraster (irregular echinoids, Spatangoida) is one of the most famous examples of a continuous evolutionary lineage in invertebrate palaeontology. The influence of the environment on the phenotype, however, was not tested so far. This study analyses differences in phenotypical variations within three populations of Micraster (Gibbaster) brevis from the early Coniacian, two from the Munsterland Cretaceous Basin (Germany) and one from the North Cantabrian Basin (Spain). The environments of the Spanish and the German sites differed by their sedimentary characteristics, which are generally a crucial factor for morphological adaptations in echinoids. Most of the major phenotypical variations (position of the ambitus, periproct and development of the subanal fasciole) among the populations can be linked to differences in their host sediments. These phenotypic variations are presumed to be an expression of phenotpic plasticiy, which has not been considered in Micraster in previous studies. Two populations (Erwitte area, Germany; Liencres area, Spain) were tested for stochastic variation (fluctuating asymmetry) due to developmental instability, which was present in all studied traits. However, differences in the amount of fluctuating asymmetry between both populations were recognised only in one trait (amount of pore pairs in the anterior paired petals). The results strengthen previous assumptions on ecophenotypic variations in Micraster. PMID- 26849650 TI - Correction: Optogenetics in Mice Performing a Visual Discrimination Task: Measurement and Suppression of Retinal Activation and the Resulting Behavioral Artifact. PMID- 26849649 TI - Evaluating the Metal Tolerance Capacity of Microbial Communities Isolated from Alberta Oil Sands Process Water. AB - Anthropogenic activities have resulted in the intensified use of water resources. For example, open pit bitumen extraction by Canada's oil sands operations uses an estimated volume of three barrels of water for every barrel of oil produced. The waste tailings-oil sands process water (OSPW)-are stored in holding ponds, and present an environmental concern as they are comprised of residual hydrocarbons and metals. Following the hypothesis that endogenous OSPW microbial communities have an enhanced tolerance to heavy metals, we tested the capacity of planktonic and biofilm populations from OSPW to withstand metal ion challenges, using Cupriavidus metallidurans, a known metal-resistant organism, for comparison. The toxicity of the metals toward biofilm and planktonic bacterial populations was determined by measuring the minimum biofilm inhibitory concentrations (MBICs) and planktonic minimum inhibitory concentrations (MICs) using the MBEC TM assay. We observed that the OSPW community and C. metallidurans had similar tolerances to 22 different metals. While thiophillic elements (Te, Ag, Cd, Ni) were found to be most toxic, the OSPW consortia demonstrated higher tolerance to metals reported in tailings ponds (Al, Fe, Mo, Pb). Metal toxicity correlated with a number of physicochemical characteristics of the metals. Parameters reflecting metal-ligand affinities showed fewer and weaker correlations for the community compared to C. metallidurans, suggesting that the OSPW consortia may have developed tolerance mechanisms toward metals present in their environment. PMID- 26849651 TI - The Presence of Pretreated Lignocellulosic Solids from Birch during Saccharomyces cerevisiae Fermentations Leads to Increased Tolerance to Inhibitors--A Proteomic Study of the Effects. AB - The fermentation performance of Saccharomyces cerevisiae in the cellulose to ethanol conversion process is largely influenced by the components of pretreated biomass. The insoluble solids in pretreated biomass predominantly constitute cellulose, lignin, and -to a lesser extent- hemicellulose. It is important to understand the effects of water-insoluble solids (WIS) on yeast cell physiology and metabolism for the overall process optimization. In the presence of synthetic lignocellulosic inhibitors, we observed a reduced lag phase and enhanced volumetric ethanol productivity by S. cerevisiae CEN.PK 113-7D when the minimal medium was supplemented with WIS of pretreated birch or spruce and glucose as the carbon source. To investigate the underlying molecular reasons for the effects of WIS, we studied the response of WIS at the proteome level in yeast cells in the presence of acetic acid as an inhibitor. Comparisons were made with cells grown in the presence of acetic acid but without WIS in the medium. Altogether, 729 proteins were detected and quantified, of which 246 proteins were significantly up-regulated and 274 proteins were significantly down-regulated with a fold change>=1.2 in the presence of WIS compared to absence of WIS. The cells in the presence of WIS up-regulated several proteins related to cell wall, glycolysis, electron transport chain, oxidative stress response, oxygen and radical detoxification and unfolded protein response; and down-regulated most proteins related to biosynthetic pathways including amino acid, purine, isoprenoid biosynthesis, aminoacyl-tRNA synthetases and pentose phosphate pathway. Overall, the identified differentially regulated proteins may indicate that the likelihood of increased ATP generation in the presence of WIS was used to defend against acetic acid stress at the expense of reduced biomass formation. Although, comparative proteomics of cells with and without WIS in the acetic acid containing medium revealed numerous changes, a direct effect of WIS on cellular physiology remains to be investigated. PMID- 26849652 TI - Is adenosine a modulator of peripheral vasoconstrictor responses? AB - BACKGROUND: Local vasoconstrictor reflexes, the vascular myogenic response (VMR) and the veno-arterial reflex (VAR) are necessary for the maintenance of regional blood flow and systemic arterial blood pressure during orthostatic stress. Their molecular mechanism is unknown. We postulated that adenosine is involved in the activation of these local reflexes. METHODS: This hypothesis was tested in 10 healthy male volunteers (age 29 +/- 3 years, BMI 24 +/- 1 kg/m(2)). We used veno occlusive plethysmography method for the assessment of forearm arterial blood flow at baseline and upon causing local venous congestion by inflating a second cuff to 40 mmHg for 4 min (VAR) and during placement of the forearm 40 cm below cardiac level for 4 min (VMR). These measurements were repeated after local infusion of either saline or aminophylline, non-selective adenosine blockers, using the Bier block method. RESULTS: Rest baseline forearm blood flow was comparable in both arms. Saline did not affect the baseline forearm blood flow. However, aminophylline causes a significant increase in baseline forearm blood flow of 34 +/- 6 % (p = 0.002). VAR demonstrated a decrease in forearm blood flow of 49 +/- 4.5 % and after saline infusion it remained unchanged, 49 +/- 5 % (p = 0.92). However, aminophylline causes significant decrease in the VAR by 35 +/- 3 % (p = 0.02). But, both, saline and aminophylline did not affect the VMR. CONCLUSION: Arterial vasoconstriction triggered by venous congestion, which is the veno-arterial reflexis seems to be modulated by adenosine, at least partially. This "sensory" reflex requires further pharmacologic physiologic investigation. PMID- 26849654 TI - A Fast and Practical Yeast Transformation Method Mediated by Escherichia coli Based on a Trans-Kingdom Conjugal Transfer System: Just Mix Two Cultures and Wait One Hour. AB - Trans-kingdom conjugation is a phenomenon by which DNA is transferred into a eukaryotic cell by a bacterial conjugal transfer system. Improvement in this method to facilitate the rapid co-cultivation of donor bacterial and recipient eukaryotic cell cultures could make it the simplest transformation method, requiring neither isolation of vector DNA nor preparation of competent recipient cells. To evaluate this potential advantage of trans-kingdom conjugation, we examined this simple transformation method using vector combinations, helper plasmids, and recipient Saccharomyces cerevisiae strains. Mixing donor Escherichia coli and recipient S. cerevisiae overnight cultures (50 MUL each) consistently yielded on the order of 10(1) transformants using the popular experimental strain BY4742 derived from S288c and a shuttle vector for trans kingdom conjugation. Transformation efficiency increased to the order of 10(2) using a high receptivity trans-kingdom conjugation strain. In addition, either increasing the amount of donor cells or pretreating the recipient cells with thiols such as dithiothreitol improved the transformation efficiency by one order of magnitude. This simple trans-kingdom conjugation-mediated transformation method could be used as a practical yeast transformation method upon enrichment of available vectors and donor E. coli strains. PMID- 26849655 TI - Costs and Benefits Associated with the MRSA Search and Destroy Policy in a Hospital in the Region Kennemerland, The Netherlands. AB - OBJECTIVE: The objective of this study was to analyze the costs and benefits of the MRSA Search and Destroy (S&D) policy between 2008 and 2013 in the Kennemer Gasthuis, a 400 bed teaching hospital in the region Kennemerland, the Netherlands. METHODS: A patient registration database was used to retrospectively calculate costs, including screening, isolation, follow-up, contact tracing, cleaning, treatment, deployment of extra healthcare workers, salary for an infection control practitioner (ICP) and service of isolation rooms. The estimated benefits (costs and lives when no MRSA S&D was applied) were based on a varying MRSA prevalence rate (up to 50%). RESULTS: When no MRSA S&D policy was applied, the additional costs and deaths due to MRSA bacteraemia were estimated to be ? 1,388,907 and 33 respectively (at a MRSA prevalence rate of 50%). Currently, the total costs were estimated to be ? 290,672 (? 48,445 annually) and a MRSA prevalence rate of 17.3% was considered as break-even point. Between 2008 and 2013, a total of 576 high risk patients were screened for MRSA carriage, of whom 19 (3.3%) were found to be MRSA positive. Forty-nine patients (72.1%) were found unexpectedly. CONCLUSIONS: Application of the MRSA S&D policy saves lives and money, although the high rate of unexpected MRSA cases is alarming. PMID- 26849653 TI - Heart Rate and Systolic Blood Pressure Variability in the Time Domain in Patients with Recent and Long-Standing Diabetes Mellitus. AB - Diabetes Mellitus (DM) affects the cardiovascular response of patients. To study this effect, interbeat intervals (IBI) and beat-to-beat systolic blood pressure (SBP) variability of patients during supine, standing and controlled breathing tests were analyzed in the time domain. Simultaneous noninvasive measurements of IBI and SBP for 30 recently diagnosed and 15 long-standing DM patients were compared with the results for 30 rigorously screened healthy subjects (control). A statistically significant distinction between control and diabetic subjects was provided by the standard deviation and the higher moments of the distributions (skewness, and kurtosis) with respect to the median. To compare IBI and SBP for different populations, we define a parameter, alpha, that combines the variability of the heart rate and the blood pressure, as the ratio of the radius of the moments for IBI and the same radius for SBP. As diabetes evolves, alpha decreases, standard deviation of the IBI detrended signal diminishes (heart rate signal becomes more "rigid"), skewness with respect to the median approaches zero (signal fluctuations gain symmetry), and kurtosis increases (fluctuations concentrate around the median). Diabetes produces not only a rigid heart rate, but also increases symmetry and has leptokurtic distributions. SBP time series exhibit the most variable behavior for recently diagnosed DM with platykurtic distributions. Under controlled breathing, SBP has symmetric distributions for DM patients, while control subjects have non-zero skewness. This may be due to a progressive decrease of parasympathetic and sympathetic activity to the heart and blood vessels as diabetes evolves. PMID- 26849658 TI - Whole Transcriptome Analysis of Hypertension Induced Cardiac Injury Using Deep Sequencing. AB - BACKGROUND/AIMS: Hypertension plays a critical role in the cardiac inflammation and injury. However, the mechanism of how hypertension causes the cardiac injury at a molecular level remains to be elucidated. METHODS: RNA-Seq has been demonstrated to be an effective approach for transcriptome analysis, which is essential to reveal the molecular constituents of cells and tissues. In this study, we investigated the global molecular events associated with the mechanism of hypertension induced cardiac injury using RNA-Seq analysis. RESULTS: Our results showed that totally 1,801 genes with different expression variations were identified after Ang II infusion at 1, 3 and 7 days. Go analysis showed that the top 5 high enrichment Go terms were response to stress, response to wounding, cellular component organization, cell activation and defense response. KEGG pathway analysis revealed the top 5 significantly overrepresented pathways were associated with ECM-receptor interaction, focal adhesion, protein digestion and absorption, phagosome and asthma. Moreover, protein-protein interaction network analysis indicated that ubiquitin C may play a key role in the processes of hypertension-induced cardiac injury. CONCLUSION: Our study provides a comprehensive understanding of the transcriptome events in hypertension-induced cardiac pathology. PMID- 26849659 TI - Link Prediction in Weighted Networks: A Weighted Mutual Information Model. AB - The link-prediction problem is an open issue in data mining and knowledge discovery, which attracts researchers from disparate scientific communities. A wealth of methods have been proposed to deal with this problem. Among these approaches, most are applied in unweighted networks, with only a few taking the weights of links into consideration. In this paper, we present a weighted model for undirected and weighted networks based on the mutual information of local network structures, where link weights are applied to further enhance the distinguishable extent of candidate links. Empirical experiments are conducted on four weighted networks, and results show that the proposed method can provide more accurate predictions than not only traditional unweighted indices but also typical weighted indices. Furthermore, some in-depth discussions on the effects of weak ties in link prediction as well as the potential to predict link weights are also given. This work may shed light on the design of algorithms for link prediction in weighted networks. PMID- 26849656 TI - Impact of Community-Based DOT on Tuberculosis Treatment Outcomes: A Systematic Review and Meta-Analysis. AB - BACKGROUND: Poor adherence to tuberculosis (TB) treatment can lead to prolonged infectivity and poor treatment outcomes. Directly observed treatment (DOT) seeks to improve adherence to TB treatment by observing patients while they take their anti-TB medication. Although community-based DOT (CB-DOT) programs have been widely studied and promoted, their effectiveness has been inconsistent. The aim of this study was to critical appraise and summarize evidence of the effects of CB-DOT on TB treatment outcomes. METHODS: Studies published up to the end of February 2015 were identified from three major international literature databases: Medline/PubMed, EBSCO, and EMBASE. Unpublished data from the grey literature were identified through Google and Google Scholar searches. RESULTS: Seventeen studies involving 12,839 pulmonary TB patients (PTB) in eight randomized controlled trials (RCTs) and nine cohort studies from 12 countries met the criteria for inclusion in this review and 14 studies were included in meta analysis. Compared with clinic-based DOT, pooled results of RCTs for all PTB cases (including smear-negative or -positive, new or retreated TB cases) and smear-positive PTB cases indicated that CB-DOT promoted successful treatment [pooled RRs (95%CIs): 1.11 (1.02-1.19) for all PTB cases and 1.11 (1.02-1.19) for smear-positive PTB cases], and completed treatment [pooled RRs (95%CIs): 1.74(1.05, 2.90) for all PTB cases and 2.22(1.16, 4.23) for smear-positive PTB cases], reduced death [pooled RRs (95%CIs): 0.44 (0.26-0.72) for all PTB cases and 0.39 (0.23-0.66) for smear-positive PTB cases], and transfer out [pooled RRs (95%CIs): 0.37 (0.23-0.61) for all PTB cases and 0.42 (0.25-0.70) for smear positive PTB cases]. Pooled results of all studies (RCTs and cohort studies) with all PTB cases demonstrated that CB-DOT promoted successful treatment [pooled RR (95%CI): 1.13 (1.03-1.24)] and curative treatment [pooled RR (95%CI): 1.24 (1.04 1.48)] compared with self-administered treatment. CONCLUSIONS: CB-DOT did improved TB treatment outcomes according to the pooled results of included studies in this review. Studies on strategies for implementation of patient centered and community-centered CB-DOT deserve further attention. PMID- 26849661 TI - beta-Catenin Expression in Oropharyngeal Squamous Cell Carcinomas: Comparison and Correlation with p16 and Human Papillomavirus in situ Hybridization. AB - BACKGROUND: The Wnt/beta-catenin signaling pathway has been noted to be upregulated in head and neck cancers, including oropharyngeal squamous cell carcinoma (OSCC). This study compared the efficacy of beta-catenin immunohistochemistry (IHC), p16 IHC and automated human papillomavirus (HPV) in situ hybridization (ISH) in OSCC. METHODS: Sixty-eight OSCCs (48 surgical specimens and 20 fine-needle aspirations) were evaluated. Nuclear staining only of beta-catenin was assessed as 0-3+ intensity (relative to controls of benign squamous mucosa). p16 was interpreted as positive if 70% of tumor cells showed brown nuclear and cytoplasmic staining. HPV ISH was interpreted as positive if a minimum of one tumor cell showed brown punctate dot-like nuclear positivity. p16 IHC and HPV ISH were then correlated with beta-catenin staining. HPV ISH was used as the gold standard. RESULTS: Twenty-five of 48 surgical specimens (52.1%) and 11 of 20 cell blocks (55%) stained positively for beta-catenin, making a total of 36 of 68 (52.9%) staining positively for beta-catenin, as compared to 61.7% positive for p16 IHC and 70.6% positive by automated HPV ISH, the gold standard method for OSCC diagnosis. x03C7;2 analysis revealed no significant correlation between beta-catenin and HPV ISH (p > 0.05) and demonstrated a strong correlation between p16 and HPV ISH (p < 0.05). CONCLUSION: beta-Catenin IHC is not a sensitive or specific marker of HPV and is unlikely to be a useful adjunct to p16 IHC or HPV ISH in the setting of advanced OSCC. However, as this study focused on samples of advanced OSCC, beta-catenin IHC may still find some use in the diagnosis of early-stage OSCC. PMID- 26849660 TI - Particle Radiation Therapy for Gastrointestinal Cancers. AB - Particle irradiation of cancerous disease has gained great traction in recent years. The ability for particle therapy centers to deliver radiation with a highly conformal dose distribution while maintaining minimal exit or excess dose delivered to normal tissue, coupled with various biological advantages particularly found with heavy-ion beams, enables treatment of diseases inapproachable with conventional radiotherapy. Here, we present a review of the current status of particle therapy with regard to cancers of the gastrointestinal tract, including esophagus, liver, pancreas, and recurrent rectal cancer. PMID- 26849665 TI - Nanoarchitectonics for Advanced Materials: Strategy Beyond Nanotechnology. PMID- 26849662 TI - Developing a Correct System to Evaluate the Accuracy of Gleason Score in Prostate Cancer of Chinese Population. AB - INTRODUCTION: A study was conducted to develop a new correct system to improve the overall rate of Gleason sum concordance between biopsy and final pathology. MATERIALS AND METHODS: A total of 592 consecutive patients who had undergone transrectal ultrasound-guided prostate biopsy and radical prostatectomy were evaluated during the first stage. Age, PSA, PSA density (PSAD), biopsy cores, positive cores, prostate volume, positive core rate (PCR), core volume rate (CVR) and digital rectal examination findings were considered predictive factors. A multiple logistic regression analysis involving a backward elimination selection procedure and linear regression analysis involving a stepwise procedure were applied to select independent predictors. RESULTS: Positive cores, PCR, CVR and PSAD were included in our assessing credibility model in the first stage. A significantly higher area under the receiver-operating curve was obtained in our model compared with CVR alone (0.641 vs. 0.517). In the second stage, patients with credibility of pre-operative Gleason score <0.388 were subjected to further evaluation. Compared with the 2 statuses, the rate of overall concordance was significantly increased (60.3 vs. 50.2%, p = 0.002). CONCLUSIONS: We developed a follow-up strategy based on the new and correct system, which represents an important consideration procedure when clinicians make decisions with regard to treatment plans. PMID- 26849668 TI - Cell Death Induction by the Indirubin Derivative 7BIO and the BH3 Mimetic Drugs ABT-737 and GX15-070 in Medullary Thyroid Carcinoma Cells. AB - PURPOSE: Patients with advanced and metastasized medullary thyroid carcinoma are difficult to treat since tumor cells do not respond to chemotherapeutic treatment and external radiation. Direct induction of cell death is a new therapeutic approach to therapy-resistant tumor cells. In this study we analyzed the effect of the indirubin-derivative 7BIO and the BH3 mimetic drugs ABT-737 and GX15-070 on cell death induction of TT medullary thyroid carcinoma cells. METHODS: TT medullary thyroid carcinoma cell line was treated with 7BIO, ABT-737 and GX15 070. Cell viability was analyzed by MTT assay, while cell death was determined by caspase 3/7 activity, measurement of caspase cleavage products and lactate dehydrogenase liberation assay. LC3B cleavage was analyzed by western blot. RESULTS: Incubation with all 3 drugs efficiently decreased the number of viable TT cells with IC50 values of 4.1 uM (7BIO), 0.19 uM (ABT-737) and 0.23 uM (GX15 070). The BH3 mimetic ABT-737 caused an apoptotic cell death with caspase activation as expected, while 7BIO- and GX15-070-treatment led to a mixed kind of cell death, where caspase activation was detected but had no effect on viability of TT cells. LC3 conversion as a biochemical marker of autophagic cell death was observed after GX15-070 treatment while LDH release pointed to involvement of necrosis after treatment with all 3 drugs. CONCLUSION: The BH3 mimetic drugs ABT 737 and GX15-070 efficiently killed TT medullary thyroid carcinoma cells with low IC50 values, while the indirubin-derivative 7BIO was also effective but with a higher IC50 value. Although the exact kind of cell death and target molecules of 7BIO and GX15-070 are not yet defined, direct induction of cell death may be a new therapeutic option in medullary thyroid carcinoma cells. PMID- 26849669 TI - Effect of Lipoic Acid on Serum Paraoxonase-1 and Paraoxonase-3 Protein Levels and Activities in Diabetic Rats. AB - The aim of the present study was to investigate the effect of streptozotocin induced diabetes mellitus and lipoic acid treatment on serum paraoxonase-1 and paraoxonase-3 protein levels and paraoxonase, arylesterase and lactonase activities.36 rats were equally and randomly divided into 4 groups as control, lipoic acid, diabetes and diabetes+lipoic acid. To induce diabetes, a single dose of streptozotocin (40 mg/kg) was injected intraperitoneally to diabetes and diabetes+lipoic acid groups. Lipoic acid (10 mg/kg/day) was injected intraperitoneally for 14 days to lipoic acid and diabetes+lipoic acid groups. Serum PON1 and PON3 protein levels were measured by western blotting. Serum paraoxonase, arylesterase and lactonase activities were determined by the measuring initial rate of substrate (paraoxon, phenylacetate and dihydrocoumarin) hydrolysis.Streptozotocin-induced diabetes mellitus caused a significant decrease whereas lipoic acid treatment caused a significant increase in serum PON1 and PON3 protein levels and paraoxonase, arylesterase and lactonase activities. The increase percent of serum PON3 protein was higher than that of serum PON1 protein and the increase percent of serum lactonase activity was higher than that of serum paraoxonase and arylesterase activities in diabetes+lipoic acid group.We can report that, like PON1 protein, PON3 protein and actually its lactonase activity may also have a role as an antioxidant in diabetes mellitus and lipoic acid treatment may be useful for the prevention of the atherosclerotic complications of diabetes by increasing serum PON1 and PON3 protein levels and serum enzyme activities. PMID- 26849670 TI - Isolation and functional characterization of a R2R3-MYB regulator of the anthocyanin biosynthetic pathway from Epimedium sagittatum. AB - KEY MESSAGE: A R2R3-MYB transcription factor EsAN2 was isolated from Epimedium sagittatum and functionally characterized to regulate the anthocyanin biosynthetic pathway. Epimedium plants are used widely both as traditional Chinese medicinal herbs and ornamental perennials. Anthocyanins, acting as major contributors to plant color diversity, their biosynthesis are regulated by a series of transcription factors, including MYB, bHLH and WD40 protein. Previously, a MYB transcription factor involved in regulation of the anthocyanin pathway from Epimedium sagittatum, EsMYBA1 has been isolated, but was found to be expressed mostly in leaves. In this research, another MYB transcription factor, designated as EsAN2, was isolated from flowers by the screening of E. sagittatum EST database. Preferential expression of EsAN2 in flowers and flower buds was found. Ectopic expression of EsAN2 in tobacco significantly enhanced the anthocyanin biosynthesis and accumulation, both in leaves and flowers. Most structural genes of the anthocyanin biosynthetic pathway were strongly upregulated, as well as two bHLH regulators (NtAn1a and NtAn1b) in old leaves of tobacco overexpressing EsAN2, compared to the control plants. While only three structural genes, chalcone synthase (CHS), chalcone isomerase (CHI) and anthocyanidin synthase (ANS), were upregulated by EsAN2 ectopic expression in tobacco flowers. Yeast two-hybrid assay showed that EsAN2 was capable of interacting with four bHLH regulators of the anthocyanin biosynthetic pathway. These results suggest that EsAN2 is involved in regulation of the anthocyanin biosynthesis in Epimedium flowers. Identification and characterization of EsAN2 provide insight into the coloration of Epimedium flowers and a potential candidate gene for metabolic engineering of flavonoids in the future. PMID- 26849673 TI - Application of SELDI-TOF in N-glycopeptides profiling of the urine from patients with endometrial, ovarian and cervical cancer. AB - PURPOSE: Endometrial (ECa), ovarian (OCa) and cervical (CCa) cancers are among 10 of the most common cancers affecting women worldwide. Cancers are known to cause some proteins to be differentially glycosylated or aberrantly excreted in the urine, which can be used as biomarkers. Since ECa, OCa and CCa are difficult to diagnose at the early stage, the aim of the present study was to identify a panel of new biomarkers for early detection of the cancers using surface-enhanced laser desorption/ionization-time-of-flight (SELDI-TOF) technology. Identification of early biomarkers that are specific and efficient can increase the survival rate of the patients. EXPERIMENTAL DESIGN: Digested urinary proteins from patients with ECa, OCa and CCa were incubated on the champedak mannose-binding (CMB) lectin-immobilized PS10 chip. The lectin-captured glycopeptides were detected with SELDI-TOF mass spectrometry and followed by biomarker wizard analysis. RESULTS: Peaks m/z 1201 and 1449 were detected as potential group discriminators. The peak m/z 1201 could distinguish OCa from CCa and ECa and its sensitivity and specificity were 100%. For m/z 1449, it was able to differentiate ECa from the other two types of cancer. CONCLUSIONS: The findings of this study suggest urinary glycopeptides m/z 1201 and 1449 may serve as potential biomarkers for the early detection of ECa, OCa and CCa, although this requires further extensive validation on clinically representative populations. PMID- 26849672 TI - Characterization of NtREL1, a novel root-specific gene from tobacco, and upstream promoter activity analysis in homologous and heterologous hosts. AB - KEY MESSAGE: A novel root-specific gene and its upstream promoter were cloned and characterized for potential application in root-specific expression of transgenes. The root is an important plant organ subjected to many biotic and abiotic stresses, such as infection by Ralstonia solanacearum. To isolate tobacco root-specific promoters for genetic applications, microarray screening was performed to identify genes highly and specifically expressed in the root. One root-specific gene encoding an extensin-like protein (NtREL1) was isolated, and its expression pattern was further characterized by both microarray analysis and reverse transcription-polymerase chain reaction. NtREL1 was highly expressed only in roots but not in any other organ. NtREL1 expression was affected by hormone treatment (salicylic acid, abscisic acid, and ethephon) as well as low temperature, drought, and R. solanacearum infection. A full-length 849 bp cDNA containing a 657-nucleotide open reading frame was cloned by Rapid Amplification of cDNA Ends. Subsequently, a fragment of 1,574 bp upstream of NtREL1 was isolated by flanking PCR and named pNtREL1. This promoter fragment contains TATA, GATA, and CAAT-boxes, the basic elements of a promoter, and six root-specific expression elements, namely OSE1, OSE2, ROOTMOTIFTAPOX1, SURECOREATSULTR11, P1BS, and WUSATAg. A construct containing the bacterial uidA reporter gene (beta glucuronidase, GUS) driven by the pNtREL1 promoter was transformed into tobacco plants. GUS staining was only detected in the root, but not in leaves and stems. Additionally, transgenic tobacco plants containing peanut resveratrol synthase gene (AhRS) driven by the pNtREL1 promoter produced resveratrol only in the root. Thus, the pNtREL1 promoter can be used to direct root-specific expression of target genes to protect the root from stress or for biological studies. PMID- 26849671 TI - Role of salicylic acid in resistance to cadmium stress in plants. AB - KEY MESSAGE: We review and introduce the importance of salicylic acid in plants under cadmium stress, and provide insights into potential regulatory mechanisms for alleviating cadmium toxicity. Cadmium (Cd) is a widespread and potentially toxic environmental pollutant, originating mainly from rapid industrial processes, the application of fertilizers, manures and sewage sludge, and urban activities. It is easily taken up by plants, resulting in obvious toxicity symptoms, including growth retardation, leaf chlorosis, leaf and root necrosis, altered structures and ultrastructures, inhibition of photosynthesis, and cell death. Therefore, alleviating Cd toxicity in plants is a major aim of plant research. Salicylic acid (SA) is a ubiquitous plant phenolic compound that has been used in many plant species to alleviate Cd toxicity by regulating plant growth, reducing Cd uptake and distribution in plants, protecting membrane integrity and stability, scavenging reactive oxygen species and enhancing antioxidant defense system, improving photosynthetic capacity. Furthermore, SA functions as a signaling molecule involved in the expression of several important genes. Significant amounts of research have focused on understanding SA functions and signaling in plants under Cd stress, but several questions still remain unanswered. In this article, the influence of SA on Cd-induced stress in plants and the potential regulation mechanism for alleviating Cd toxicity are reviewed. PMID- 26849674 TI - Microbial Diversity in Cerrado Biome (Neotropical Savanna) Soils. AB - The Cerrado, the largest savanna region in South America, is located in central Brazil. Cerrado physiognomies, which range from savanna grasslands to forest formations, combined with the highly weathered, acidic clay Cerrado soils form a unique ecoregion. In this study, high-throughput sequencing of ribosomal RNA genes was combined with shotgun metagenomic analysis to explore the taxonomic composition and potential functions of soil microbial communities in four different vegetation physiognomies during both dry and rainy seasons. Our results showed that changes in bacterial, archaeal, and fungal community structures in cerrado denso, cerrado sensu stricto, campo sujo, and gallery forest soils strongly correlated with seasonal patterns of soil water uptake. The relative abundance of AD3, WPS-2, Planctomycetes, Thermoprotei, and Glomeromycota typically decreased in the rainy season, whereas the relative abundance of Proteobacteria and Ascomycota increased. In addition, analysis of shotgun metagenomic data revealed a significant increase in the relative abundance of genes associated with iron acquisition and metabolism, dormancy, and sporulation during the dry season, and an increase in the relative abundance of genes related to respiration and DNA and protein metabolism during the rainy season. These gene functional categories are associated with adaptation to water stress. Our results further the understanding of how tropical savanna soil microbial communities may be influenced by vegetation covering and temporal variations in soil moisture. PMID- 26849675 TI - Paul I. Terasaki, PhD, 1929-2016. AB - Paul Terasaki was a pioneer of transplantation and had a global following. His career, which spanned >50 years, included accomplishments and discoveries that revolutionized the field of transplantation and that advanced the care of transplant patients. Paul is survived by his wife Hisako, his brother, four children and six grandchildren as well as legions of close friends and colleagues around the world who will continue to build on his successes. PMID- 26849676 TI - C-Peptide Level in Fasting Plasma and Pooled Urine Predicts HbA1c after Hospitalization in Patients with Type 2 Diabetes Mellitus. AB - In this study, we investigate how measures of insulin secretion and other clinical information affect long-term glycemic control in patients with type 2 diabetes mellitus. Between October 2012 and June 2014, we monitored 202 diabetes patients who were admitted to the hospital of Asahi Life Foundation for glycemic control, as well as for training and education in diabetes management. We measured glycated hemoglobin (HbA1c) six months after discharge to assess disease management. In univariate analysis, fasting plasma C-peptide immunoreactivity (F CPR) and pooled urine CPR (U-CPR) were significantly associated with HbA1c, in contrast to DeltaCPR and C-peptide index (CPI). This association was strongly independent of most other patient variables. In exploratory factor analysis, five underlying factors, namely insulin resistance, aging, sex differences, insulin secretion, and glycemic control, represented patient characteristics. In particular, insulin secretion and resistance strongly influenced F-CPR, while insulin secretion affected U-CPR. In conclusion, the data indicate that among patients with type 2 diabetes mellitus, F-CPR and U-CPR may predict improved glycemic control six months after hospitalization. PMID- 26849677 TI - Commentary: Linking Cortical and Subcortical Developmental Trajectories to Behavioral Deficits in a Mouse Model of Prenatal Alcohol Exposure. PMID- 26849678 TI - Marginally low birthweight increases the risk of underweight and short stature at three and a half years of age. AB - AIM: Little is known about the long-term health of marginally low birthweight (LBW) children. This study characterised growth among infants weighing 2000 g 2500 g and explored the prevalence and predictors of sustained growth restriction. METHOD: This prospective observational trial followed the weight and height of 281 Swedish marginally LBW children from birth to 3.5 years of age. Children with a standard deviation score (SDS) for body mass index or height below -2 were considered underweight and short, respectively. RESULTS: The mean SDS for weight and height showed a rapid increase before 12-19 weeks of age. The most rapid weight gain was in infants born small for gestational age. However, at 3.5 years of age, 9.5% of the children remained underweight and 6.5% had short stature. Regression models showed that slow weight gain before 19 weeks of age was the strongest predictor for lasting underweight, while slow height gain before 19 weeks of age and male sex were associated with short stature. CONCLUSION: Marginally LBW infants were more likely to be underweight and have a short stature at 3.5 years of age and the absence of catch-up growth during the first five months after birth identified those at highest risk. PMID- 26849679 TI - Factors Influencing the Prescription of Cardiovascular Preventive Therapies in Patients with Peripheral Arterial Disease. AB - BACKGROUND: Guidelines recommend that patients with peripheral arterial disease should be medically treated to reduce the occurrence of serious cardiovascular events. Despite these recommendations, studies conducted in the early 2000s reported that medical therapies for secondary cardiovascular prevention are not given systematically to patients with peripheral arterial disease (PAD). We identified factors associated with the prescription of preventive therapies in patients with symptomatic PAD. METHODS AND FINDINGS: Consecutive patients with symptomatic peripheral arterial disease (n = 362) treated between 2008 and 2010 in one tertiary care center (CHU de Quebec, Canada) were considered. Data were collected from the medical charts. The main outcome was the combined prescription of three therapies: 1) statins, 2) antiplatelets, 3) angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The mean age was 70 years and 43% had a pre-existing coronary artery disease. Antiplatelet therapy was the most prescribed drug (83%). A total of 52% of the patients received the three combined therapies. Less than 10% of patients had a known contraindication to one class of medication. Having at least three cardiovascular risk factors (Odds Ratio (OR) = 4.51; 95% CI: 2.76-7.37) was the factor most strongly associated with the prescription of the combined therapies. Pre-existing coronary artery disease (OR = 2.28; 95% CI: 1.43-3.65) and history of peripheral vascular surgery (OR = 2.30; 95% CI: 1.37-3.86) were two factors independently associated with the prescription of the combined therapies. However, peripheral arterial disease patients with chronic critical limb ischemia were less likely to receive the combined therapies (OR = 0.53; 95% CI: 0.32-0.87) than those with claudication. The retrospective nature of this study, not allowing for an exhaustive report of the contraindication to medication prescription, is the main limitation. CONCLUSION: About half of the patients with peripheral arterial disease were not optimally managed. Patients with multiple cardiovascular risk factors were more likely to receive the combined therapies. We still need to better understand the barriers and facilitators to the application of the guidelines. PMID- 26849680 TI - Application of a Persistent Heparin Treatment Inhibits the Malignant Potential of Oral Squamous Carcinoma Cells Induced by Tumor Cell-Derived Exosomes. AB - Exosomes are 30-100 nm-sized membranous vesicles, secreted from a variety of cell types into their surrounding extracellular space. Various exosome components including lipids, proteins, and nucleic acids are transferred to recipient cells and affect their function and activity. Numerous studies have showed that tumor cell-derived exosomes play important roles in tumor growth and progression. However, the effect of exosomes released from oral squamous cell carcinoma (OSCC) into the tumor microenvironment remains unclear. In the present study, we isolated exosomes from OSCC cells and investigated the influence of OSCC cell derived exosomes on the tumor cell behavior associated with tumor development. We demonstrated that OSCC cell-derived exosomes were taken up by OSCC cells themselves and significantly promoted proliferation, migration, and invasion through the activation of the PI3K/Akt, MAPK/ERK, and JNK-1/2 pathways in vitro. These effects of OSCC cell-derived exosomes were obviously attenuated by treatment with PI3K, ERK-1/2, and JNK-1/2 pharmacological inhibitors. Furthermore, the growth rate of tumor xenografts implanted into nude mice was promoted by treatment with OSCC cell-derived exosomes. The uptake of exosomes by OSCC cells and subsequent tumor progression was abrogated in the presence of heparin. Taken together, these data suggest that OSCC cell-derived exosomes might be a novel therapeutic target and the use of heparin to inhibit the uptake of OSCC-derived exosomes by OSCC cells may be useful for treatment. PMID- 26849682 TI - Exploiting Publication Contents and Collaboration Networks for Collaborator Recommendation. AB - Thanks to the proliferation of online social networks, it has become conventional for researchers to communicate and collaborate with each other. Meanwhile, one critical challenge arises, that is, how to find the most relevant and potential collaborators for each researcher? In this work, we propose a novel collaborator recommendation model called CCRec, which combines the information on researchers' publications and collaboration network to generate better recommendation. In order to effectively identify the most potential collaborators for researchers, we adopt a topic clustering model to identify the academic domains, as well as a random walk model to compute researchers' feature vectors. Using DBLP datasets, we conduct benchmarking experiments to examine the performance of CCRec. The experimental results show that CCRec outperforms other state-of-the-art methods in terms of precision, recall and F1 score. PMID- 26849681 TI - In Vivo, In Vitro, and In Silico Characterization of Peptoids as Antimicrobial Agents. AB - Bacterial resistance to conventional antibiotics is a global threat that has spurred the development of antimicrobial peptides (AMPs) and their mimetics as novel anti-infective agents. While the bioavailability of AMPs is often reduced due to protease activity, the non-natural structure of AMP mimetics renders them robust to proteolytic degradation, thus offering a distinct advantage for their clinical application. We explore the therapeutic potential of N-substituted glycines, or peptoids, as AMP mimics using a multi-faceted approach that includes in silico, in vitro, and in vivo techniques. We report a new QSAR model that we developed based on 27 diverse peptoid sequences, which accurately correlates antimicrobial peptoid structure with antimicrobial activity. We have identified a number of peptoids that have potent, broad-spectrum in vitro activity against multi-drug resistant bacterial strains. Lastly, using a murine model of invasive S. aureus infection, we demonstrate that one of the best candidate peptoids at 4 mg/kg significantly reduces with a two-log order the bacterial counts compared with saline-treated controls. Taken together, our results demonstrate the promising therapeutic potential of peptoids as antimicrobial agents. PMID- 26849683 TI - Halide-Amine Co-Passivated Indium Phosphide Colloidal Quantum Dots in Tetrahedral Shape. AB - Wet chemical synthesis of covalent III-V colloidal quantum dots (CQDs) has been challenging because of uncontrolled surfaces and a poor understanding of surface ligand interactions. We report a simple acid-free approach to synthesize highly crystalline indium phosphide CQDs in the unique tetrahedral shape by using tris(dimethylamino) phosphine and indium trichloride as the phosphorus and indium precursors, dissolved in oleylamine. Our chemical analyses indicate that both the oleylamine and chloride ligands participate in the stabilization of tetrahedral shaped InP CQDs covered with cation-rich (111) facets. Based on density functional theory calculations, we propose that fractional dangling electrons of the In-rich (111) surface could be completely passivated by three halide and one primary amine ligands per the (2*2) surface unit, satisfying the 8-electron rule. This halide-amine co-passivation strategy will benefit the synthesis of stable III-V CQDs with controlled surfaces. PMID- 26849684 TI - Effects of liraglutide on no-reflow in patients with acute ST-segment elevation myocardial infarction. AB - BACKGROUND: The 'no-reflow' phenomenon after a percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) is a strong predictor of both short- and long-term mortality. Glucagon-like peptide-1 (GLP-1) exerts a cardioprotective effect during ischemia reperfusion injury. We planned to evaluate the effects of liraglutide on myocardial no-reflow after PCI for STEMI. METHODS: A total of 284 patients with STEMI undergoing PCI were enrolled in this study between September 2013 and March 2015. Of these, 210 patients were randomized 1:1 to receive either liraglutide or placebo 30 min before PCI (1.8 mg). RESULTS: The primary end point, the prevalence of no-reflow, was significantly lower in the liraglutide group than in the control group (5% vs. 15%, P=0.01). Administration of liraglutide was consistently identified as a significant determinant for no-reflow ratio. There was a significant decrease in serum high-sensitivity C-reactive protein levels at 6-hour reperfusion in the liraglutide group compared to the control group (0.87 +/- 0.09 mg/dL vs. 0.96 +/- 0.10mg/dL, P<0.001). During a 3-month follow-up period, no difference was observed in the incidence of major adverse cardiovascular event. CONCLUSIONS: Liraglutide may be associated with less no-reflow in STEMI, which should be confirmed by larger-scale trials. PMID- 26849685 TI - Outcome of direct current cardioversion for atrial arrhythmia in adult Fontan patients. AB - BACKGROUND: Limited data are available about direct current cardioversion (DCCV) in Fontan patients. METHODS: Retrospective review of adult Fontan patients that underwent DCCV for atrial arrhythmias at Mayo Clinic, 1994-2014. Study endpoints were to determine procedural success, safety, and the freedom from arrhythmia recurrence after DCCV. Procedural success was defined as termination of the presenting atrial arrhythmia prior to leaving the cardioversion suite. RESULTS: 86 patients underwent 152 DCCV; age 27 +/- 8 years; male 49 (57%); atriopulmonary Fontan, 64 (74%); atrial flutter/interatrial reentry tachycardia 125 (82%). Freedom from recurrence was 84% and 47% at 12 and 36 months; freedom from repeat DCCV was 91% and 64% at 12 and 36 months. Procedural failure occurred in 41 (27%); predictors of procedural failure were older age (HR 1.91, CI 1.16-2.73 per decade) and prior DCCV (HR 2.71, CI 1.22-3.21). Concomitant oral class I or III antiarrhythmic medication was associated with an increased likelihood of success (HR 0.64, CI 0.41-0.87). Predictors of recurrence were older age (HR 3.26, CI 1.19-6.55 per decade); duration of arrhythmia (HR 1.87, CI 1.14-2.56 per decade); and presence of atriopulmonary Fontan (HR 1.54, CI 1.27-1.85). Procedural complications were symptomatic bradycardia in 2 cases (1%). No thromboembolic complications or deaths occurred. CONCLUSION: DCCV in Fontan patients is safe but is associated with significant procedural failure and recurrence rates. Ideally, antiarrhythmic medication should be instituted prior to DCCV in stable patients and DCCV alone should be considered as a temporizing measure to maintain sinus rhythm. PMID- 26849687 TI - Do stress, health behavior, and sleep mediate the association between loneliness and adverse health conditions among older people? AB - INTRODUCTION: Prior research has established an association between loneliness and a variety of negative health conditions among older people. However, little is known about the mechanisms underlying this association. OBJECTIVE: Building on the Loneliness Model, Hawkley and Cacioppo (2010) identified possible pathways through which loneliness may affect the development of adverse health conditions. The present study was designed to test the pathways proposed by Hawkley and Cacioppo. METHODS: The sample consisted of 8593 elderly ranging from 65 to 102 years of age participating in the 2013 Public Health Survey "How are you?". RESULTS: Findings show that loneliness was significantly associated with cardiovascular disease, diabetes, and migraine. In addition high perceived stress, physical inactivity, daily smoking, and poor sleep mediated the association between loneliness and adverse health conditions. Moreover, findings demonstrate several gender differences in the association between loneliness and various adverse condition and the indirect mechanisms affecting these associations. CONCLUSION: The findings largely support the pathways proposed by Hawkley and Cacioppo. PMID- 26849686 TI - The influence of training characteristics on the effect of aerobic exercise training in patients with chronic heart failure: A meta-regression analysis. AB - Although aerobic exercise training has shown to be an effective treatment for chronic heart failure patients, there has been a debate about the design of training programs and which training characteristics are the strongest determinants of improvement in exercise capacity. Therefore, we performed a meta regression analysis to determine a ranking of the individual effect of the training characteristics on the improvement in exercise capacity of an aerobic exercise training program in chronic heart failure patients. We focused on four training characteristics; session frequency, session duration, training intensity and program length, and their product; total energy expenditure. A systematic literature search was performed for randomized controlled trials comparing continuous aerobic exercise training with usual care. Seventeen unique articles were included in our analysis. Total energy expenditure appeared the only training characteristic with a significant effect on improvement in exercise capacity. However, the results were strongly dominated by one trial (HF-action trial), accounting for 90% of the total patient population and showing controversial results compared to other studies. A repeated analysis excluding the HF-action trial confirmed that the increase in exercise capacity is primarily determined by total energy expenditure, followed by session frequency, session duration and session intensity. These results suggest that the design of a training program requires high total energy expenditure as a main goal. Increases in training frequency and session duration appear to yield the largest improvement in exercise capacity. PMID- 26849688 TI - A Generalized QMRA Beta-Poisson Dose-Response Model. AB - Quantitative microbial risk assessment (QMRA) is widely accepted for characterizing the microbial risks associated with food, water, and wastewater. Single-hit dose-response models are the most commonly used dose-response models in QMRA. Denoting PI(d) as the probability of infection at a given mean dose d, a three-parameter generalized QMRA beta-Poisson dose-response model, PI(d|alpha,beta,r*), is proposed in which the minimum number of organisms required for causing infection, Kmin , is not fixed, but a random variable following a geometric distribution with parameter 0 0.05), when adjusted for total body fat mass. There were no associations between estradiol tertiles and BMDs, or with cIMT or CAC. Adiponectin levels were inversely associated with femoral neck BMD (p = 0.019, beta = -0.138) and total body BMD (p = 0.009, beta = -0.142), adjusted for total body fat mass, age, current smoking and estradiol, but showed no relationship with CAC or cIMT. Leptin levels were not associated with BMDs or cIMT; but the odds ratio was 1.5 between the CAC and leptin quartiles (p = 0.014), adjusted for total body fat mass, age, statin use and calcium intake. CONCLUSION: The adipokines are associated with vascular calcification and low BMD. Moreover, estradiol was not independently associated with BMD or CAC. PMID- 26849747 TI - Plasticity and evolution in correlated suites of traits. AB - When organisms are faced with new or changing environments, a central challenge is the coordination of adaptive shifts in many different phenotypic traits. Relationships among traits may facilitate or constrain evolutionary responses to selection, depending on whether the direction of selection is aligned or opposed to the pattern of trait correlations. Attempts to predict evolutionary potential in correlated traits generally assume that correlations are stable across time and space; however, increasing evidence suggests that this may not be the case, and flexibility in trait correlations could bias evolutionary trajectories. We examined genetic and environmental influences on variation and covariation in a suite of behavioural traits to understand if and how flexibility in trait correlations influences adaptation to novel environments. We tested the role of genetic and environmental influences on behavioural trait correlations by comparing Trinidadian guppies (Poecilia reticulata) historically adapted to high- and low-predation environments that were reared under native and non-native environmental conditions. Both high- and low-predation fish exhibited increased behavioural variance when reared under non-native vs. native environmental conditions, and rearing in the non-native environment shifted the major axis of variation among behaviours. Our findings emphasize that trait correlations observed in one population or environment may not predict correlations in another and that environmentally induced plasticity in correlations may bias evolutionary divergence in novel environments. PMID- 26849746 TI - Molecular evolution of troponin I and a role of its N-terminal extension in nematode locomotion. AB - The troponin complex, composed of troponin T (TnT), troponin I (TnI), and troponin C (TnC), is the major calcium-dependent regulator of muscle contraction, which is present widely in both vertebrates and invertebrates. Little is known about evolutionary aspects of troponin in the animal kingdom. Using a combination of data mining and functional analysis of TnI, we report evidence that an N terminal extension of TnI is present in most of bilaterian animals as a functionally important domain. Troponin components have been reported in species in most of representative bilaterian phyla. Comparison of TnI sequences shows that the core domains are conserved in all examined TnIs, and that N- and C terminal extensions are variable among isoforms and species. In particular, N terminal extensions are present in all protostome TnIs and chordate cardiac TnIs but lost in a subset of chordate TnIs including vertebrate skeletal-muscle isoforms. Transgenic rescue experiments in Caenorhabditis elegans striated muscle show that the N-terminal extension of TnI (UNC-27) is required for coordinated worm locomotion but not in sarcomere assembly and single muscle-contractility kinetics. These results suggest that N-terminal extensions of TnIs are retained from a TnI ancestor as a functional domain. PMID- 26849748 TI - Zika Virus: A New Chapter in the History of Medicine. PMID- 26849749 TI - [Hospital Based Public Health Doctors: Just a Part of the Future]. PMID- 26849751 TI - Detection and Intervention Strategies by Primary Health Care Professionals in Suspected Elder Abuse. AB - INTRODUCTION: Primary health care professionals are in a privileged position to recognize and manage cases of suspected elder abuse. The purpose of this study was to provide some insight of these professionals' views and knowledge on this subject. MATERIAL AND METHODS: A questionnaire was elaborated and sent to physicians and nursing staff practicing in 12 different health care units in Coimbra. The data collected included parameters related to demography, perception of abuse and management strategies, personal experience and training on this subject. RESULTS: The global response rate was 67.9% corresponding to 127 validated questionnaires. From the results found, we highlight the following: there was a significant contact between these professionals and older people; most (64.6%) considered the abuse as more prevalent in the familiar context and 32.3% signed negligence as the most common type; the majority of professionals considered themselves as useful (97.6%); the uncertainty in the diagnosis was one of the most important causes for non-reporting; there were doubts concerning mandatory report of abuse to judicial authorities. It was also found that 87.4% of the respondents stated they would feel more comfortable having formal protocol to handle these cases and this subject was not included in the training curriculum of 70.9% of the respondents. DISCUSSION: The significant contact between older population and health care professionals allows for an early diagnose and intervention. The professionals showed knowledge in accordance to some studies, namely, as to the context and prevalence of abuse. Doubts as to the best way to manage these cases could be solved by implementing protocols and by specific training, which is a fundamental cornerstone for preparing professionals to deal with these kind of cases. CONCLUSION: Health care professionals seemed to be aware of the relevance of elder abuse, as well as the importance of their role in preventing and diagnosing these abuses. However, a more extensive approach on this subject during clinical training and the definition of general clinical guidelines are important to increase the professionals' confidence in managing suspected cases. PMID- 26849750 TI - [Analysis of the Cochrane Review: Helicobacter pylori Eradication for the Prevention of Gastric Neoplasia. Cochrane Database Syst Rev. 2015;7:CD005583]. AB - Helicobacter pylori infection is a risk factor for gastric adenocarcinoma. Identification of individuals with this infection and its eradication may be considered as a primary prevention strategy to reduce the incidence of gastric adenocarcinoma; however, the magnitude of benefit and the effectiveness of this strategy are still unclear. A systematic review and meta-analysis of randomized clinical trials was conducted comparing the incidence of gastric adenocarcinoma in infected individuals submitted to Helicobacter pylori eradication and individuals not submitted to this therapy. The results of the six included randomized clinical trials (all conducted in countries with high gastric cancer incidence) suggest that Helicobacter pylori eradication is associated with a relative risk reduction of 34% in gastric cancer incidence. However, generalization of the results to countries with lower gastric cancer incidence should be cautious and the cost-effectiveness of this strategy in this context remains uncertain. PMID- 26849752 TI - [Assessment of Hepatitis C Virus Diversity in Addition to the Frequency of Genotypes in Samples Analyzed Between 2009 and 2014 at the Reference Laboratory of National Health Institute Dr. Ricardo Jorge]. AB - INTRODUCTION: The identification of genotypes was essential for the prognosis and treatment of hepatitis C virus chronic patients in recent years. The aims of the study were to know the frequency of genotypes diagnosed in the last six years at the laboratory, and reveal the contribution of an in-house assay for molecular characterization of viruses. MATERIAL AND METHODS: The genotyping of hepatitis C virus by LiPA was performed in 923 samples, mostly from male individuals. The subtyping of hepatitis C virus by an in-house assay to target regions in the Core/E1 and/or NS5B was performed in 112 samples. RESULTS: We observed a high prevalence of genotype 1 (56.6%), with a frequency of subtype 1a four times higher compared to 1b. All cases of genotype 3 (27.5%) were subtype 3a. For the cases of genotype 4 (12.9%), it were identified subtypes 4a (65.5%), 4d (31%), 4b (1.7%) and 4c (1.7%). Recombinants intragenotype 2, the RF1_2k/1b, and mixed infections, were also identified. DISCUSSION: The most prevalent subtypes (1a and 3a) obtained are usually described in injecting drug users. Although most of the samples analysed match to inmates (78.4%), we cannot exclude any possible risk behaviors associated with illicit drug use. CONCLUSIONS: The high prevalence of subtype 1a, the frequency and diversity of genotype 4, and the identification of recombined virus suggest modification of the molecular pattern of hepatitis C virus infection described in the past. The in-house assay proved to be useful for the correct classification of hepatitis C virus and improving knowledge about the diversity of virus circulating in the country. PMID- 26849753 TI - Assessment of Inhalation Technique in Clinical and Functional Control of Asthma and Chronic Obstructive Pulmonary Disease. AB - INTRODUCTION: Chronic obstructive pulmonary disease and asthma affect almost 300 million individuals. Inhaled therapy is often associated with technical errors reducing efficacy and compliance. OBJECTIVE: To evaluate the inhalation technique and its relation with clinical and functional control in asthma and chronic obstructive pulmonary disease. MATERIAL AND METHODS: Analytical cross-sectional study including patients with asthma and chronic obstructive pulmonary disease treated with any type of inhaler device. Demographic data and inquiry about previous teaching of inhalation technique were collected in all participants. Inhalation technique was evaluated in: Step 1 - device activation; Step 2 - previous expiration; Step 3 - inspiration; Step 4 - end inspiratory pause. Clinical control was assessed from the questionnaires Asthma Control Test, Control of Allergic Rhinitis and Asthma Test, modified Medical Research Council and Chronic Obstructive Pulmonary Disease Assessment Test. Spirometric evaluation was performed in all participants. RESULTS: From a total of 62 subjects, 74.19% made at least one error, mainly during step 2 (53.2%). Previous education on inhalation technique was associated with lower number of errors (p = 0.014). There was no association between number of errors and age (p = 0.321), years of diagnosis (p = 0.119) or spirometric evaluation (p > 0.05). In asthma an association was found between number of errors and Asthma Control Test (p = 0.032) and Control of Allergic Rhinitis and Asthma Test (p = 0.008). DISCUSSION AND CONCLUSION: Teaching inhalation technique has a positive impact on its future performance. Most patients make mistakes, affecting clinical control in asthma, although in chronic obstructive pulmonary disease no relation was found. This is an ongoing work that aims to reevaluate inhalation technique after patients' education and its further impact. PMID- 26849754 TI - [Congenital Anomalies Detected at Birth in Newborns of Adolescent Women]. AB - INTRODUCTION: To analyze the prevalence of congenital anomalies detected at birth among children of pregnant adolescents, emphasizing the most common types and the time of diagnosis. MATERIAL AND METHODS: Retrospective study of type census, in which were analyzed in all newborns, living or dead, weighing more than 500 g of women who gave birth at Hospital Sao Paulo in a period of six years. The fetuses bearing anomalies were identified prenatally or through postnatal physical examination period, according to the criteria of the Latin American Collaborative Study of Congenital Malformations. The results were expressed descriptively using absolute and relative values, the prevalence of anomalies was calculated, as well as the comparison between groups using nonparametric tests. RESULTS: We analyzed 6 257 pregnancies, of which 577 newborns had some congenital anomaly identified at birth (prevalence 9.2%). Among these 6 257, 907 were adolescents, which showed a 9.9% prevalence of anomalies among their newborns. There was no significant difference between the presence of abnormalities in newborns of adolescents and women with age greater than or equal to 20 years. About 56% of congenital anomalies were diagnosed in the prenatal period. We observed a higher prevalence of defects of neural tube between newborns of adolescents (p = 0.027). DISCUSSION: We observed high rate of deliveries in adolescents, higher than developed countries. We observed also high frequency of congenital anomalies in newborns, probably because our tertiary reference center. The high prevalence of neural tube defect among young pregnant women could be explained by the absent of acid folic supplementation in non-planned gestations which is typical of adolescents. CONCLUSION: The prevalence and time of diagnosis of congenital anomalies showed similar behavior among newborns of teenagers and women with age greater than or equal to 20 years, except for the defects of the neural tube, which were more prevalent among newborns of teenagers. PMID- 26849755 TI - Stigma and Attitudes towards Psychiatric Patients in Portuguese Medical Students. AB - INTRODUCTION: This study aims to assess the impact of psychiatric education on attitudes of medical students towards psychiatric patients. MATERIAL AND METHODS: A cross-sectional survey of medical students was conducted at the biggest Portuguese medical school. The students completed an anonymous self-report questionnaire, including sociodemographic data, family history of psychiatric illness, and the Community Attitudes toward the Mentally Ill scale. RESULTS: Of the 2 178 students, 398 answered the survey, representing 18.2% of the whole medical school. There was a significant improvement in all Community Attitudes toward the Mentally Ill scale dimensions along the medical course. The higher scores were in Restrictiveness subscale (38.01), and the lower scores were for Authoritarianism (36.13). The best improvement along the course was for Authoritarianism (5th year score - 1st year score = 2.03), and the worse was for Benevolence (5th year score - 1st year score = 0.39). The biggest improvement, in all scores, was found at the end of the 3rd year. DISCUSSION: The authors propose that the better attitudes found on third year students were due to a very specific anti-stigma module on the theoretical discipline 'Introduction to Mental Health'. After that, this positive effect was lost, with fourth and fifth year medical students showing a worsening of their attitudes. CONCLUSION: Our results highlight the importance of anti-stigma specific education modules in order to improve students' attitudes toward mental health. Thus more anti-stigma preventive measures can be taken onward, on preparing the best way possible, the next generation of doctors. PMID- 26849756 TI - [Serum Erythropoietin as Prognostic Marker in Myelodysplastic Syndromes]. AB - INTRODUCTION: This myelodysplastic syndromes are a heterogeneous entity characterized by dysplasia, hypercellular bone marrow, cytopenias and risk of transformation to acute leukaemia. Prognostic factors, such as bone marrow fibrosis, lactate dehydrogenase and 2-microglobulin elevation have been described, but treatment is mainly based in the International Prognostic Scoring System. MATERIAL AND METHODS: Our aim was to analyze serum's erythropoietin at diagnosis in de novo myelodysplastic syndromes patients, through its impact in overall survival and possible implementation as prognostic marker. Clinical and laboratorial data from 102 patients with de novo myelodysplastic syndromes diagnosed between October/2009 and March/2014 were collected. Survival analysis was performed according to serum erythropoietin level stratification, using Kaplan-Meier methodology. RESULTS: Our 102 patients had a median age of 74 years, with a male:female ratio of 0.8. Mean erythropoietin was significantly lower in refractory cytopenia with unilineage dysplasia patients in contrast with the higher values observed in 5q- syndrome (p < 0.05). Eleven patients progressed to acute leukaemia; these have higher mean erythropoietin values (p < 0.05). In addition, elevated serum erythropoietin was associated with lower survival rates (p = 0.0336). Predictive value of serum erythropoietin was maintained after Cox regression adjustment. In multivariate analysis, serum erythropoietin is an independent survival predictor (p < 0.001). DISCUSSION: Serum erythropoietin is a predictive factor for response to therapy with subcutaneous erythropoietin, and patients with myelodysplastic syndromes with higher values of erythropoietin have poorer response to administration of erythropoietin even at higher doses. Our sample shows that serum erythropoietin also has prognostic value, and in all myelodysplastic syndromes subtypes. Moreover, alone or in combination with other factors or prognostic indices, erythropoietin may enhance the prognostic indices such as the International Prognostic Scoring System, since high levels are associated with progression to acute leukemia and hence lower survival. CONCLUSION: This study suggests that increased erythropoietin levels at diagnosis can by itself be a poor prognosis factor inmyelodysplastic syndromes patients, with higher values in patients with progression to acute leukaemia and decreased overall survival. PMID- 26849757 TI - [Vitamin D Insufficiency in a Hospital Population: A Photograph from the Laboratory Perspective]. AB - INTRODUCTION: Although vitamin D deficiency is increasingly recognized around the world, there are few studies on the Portuguese reality. This study aims to analyse vitamin D levels in the assays performed in our hospital and their relationship with age, genre, requesting specialty and moment of sample collection. MATERIAL AND METHODS: Cross-sectional study of measurements of 25(HO)D performed in our Hospital between June 2012 and November 2014. Included variables: gender, age, requesting specialty, month of sample collection. Vitamin D status classified as: 'Deficiency' (<= 20 ng/mL), 'Insufficiency' (21 - 29 ng/ml) and 'Sufficiency' (>= 30 ng/mL). RESULTS: We included 5 439 assays; 55.0% from women; the median age was 64.0 years. Sixty per cent had 'Deficiency', 20.7% 'Insufficiency' and 18.9% 'Sufficiency'. We found a negative correlation between age and vitamin D level (p < 0.001). We didn't find differences in vitamin D levels between genres. Nine specialties requested 98% of the assays, namely Nephrology (56.2%). We found differences between specialties based on age and vitamin D level (p < 0.001). Vitamin D levels changed throughout the year, with higher levels in the summer, followed by autumn, spring and winter (p < 0.001). Despite this seasonal fluctuation, vitamin D sufficiency was only present in a minority of assays (27.8% in summer and 9.2% in winter). DISCUSSION: Vitamin D deficiency is prevalent in this population, affects individuals of all ages and is not offset by the seasonal variation of sunlight. CONCLUSION: Vitamin D deficiency is a real and prevalent problem in our population that needs further attention and action, given its clinical implications. PMID- 26849758 TI - Laparoscopic Adjustable Gastric Band: Complications, Removal and Revision in a Portuguese Highly Differentiated Obesity Treatment Center. AB - INTRODUCTION: Our objective is to determine which complications lead to reoperation, and the outcomes of reoperation using laparoscopic adjustable gastric banding, laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy at Centro Hospitalar de Sao Joao. MATERIAL AND METHODS: Observational study. Patients included were aged 18 to 65 years at first gastric banding, underwent removal from March 21st 2007 to January 23rd 2014 and were subsequently converted to gastric banding, gastric bypass or sleeve gastrectomy. Women who got pregnant during the initial gastric banding follow-up and patients that performed more than one conversion were excluded. RESULTS: A total of 103 patients were included. Fifteen underwent revision to gastric banding, 71 to gastric bypass and 17 to sleeve gastrectomy. Respectively, percentage of excess weight loss at 1 month were 1.9 +/- 12.2% in 6 patients, 36.9 +/- 18.2% in 49 patients and 27.1% (13.3 - 68.6) in 11 patients (laparoscopic adjustable-gastric banding laparoscopic Roux-en-Y gastric bypass p < 0.001, laparoscopic adjustable-gastric banding-laparoscopic sleeve gastrectomy p = 0.002 and laparoscopic Roux-en-Y gastric bypass-laparoscopic sleeve gastrectomy p = 0.474). At 3 months there were 12.8% (5.7 - 84.8) in 6 patients, 44.8 +/- 19.7% in 24 patients and 48 +/- 20.1% in 8 patients (laparoscopic adjustable-gastric banding-laparoscopic Roux-en-Y gastric bypass p = 0.017, laparoscopic adjustable-gastric banding-laparoscopic sleeve gastrectomy p = 0.039 and laparoscopic Roux-en-Y gastric bypass laparoscopic sleeve gastrectomy p = 0.691). DISCUSSION: At revision, ages and body mass indices are higher than other studies. Gastric bypass is the preferred revision surgery, because combines restriction and malabsorption, surgeons have more experience and long term outcomes are better described. CONCLUSIONS: The main indications for reoperation were inadequate weight loss (37.4%) and band slippage (30%). At short term, in our patients, gastric banding as a revision surgery was not effective, as opposed to gastric bypass and sleeve gastrectomy. PMID- 26849759 TI - [Clinical and Epidemiological Study of Complicated Infection by Varicella-Zoster Virus in the Pediatric Age]. AB - INTRODUCTION: In Portugal, the incidence of complicated infection by varicella zoster virus is unknown. The purpose of this study was to describe the epidemiological and clinical features of complicated infection by varicella zoster virus in children. MATERIAL AND METHODS: Retrospective review of the clinical files of patients admitted between January 1999 and July 2013, with a diagnosis of complicated varicella-zoster virus infection. RESULTS: Ninety-four patients were hospitalized with complicated varicella-zoster virus infection, two of them by reactivation of latent infection. The median age was 38 (IQR 18 - 65) months. The most frequent types of complications were bacterial overinfection of the skin and subcutaneous cellular tissue (37.2%) and respiratory complications (24.5%). Other complications were neurologic complications (19.1%), gastrointestinal (9.6%), hematologic (5.3%) and osteoarticular (4.3%). In 38 patients invasive bacterial infections were diagnosed, with bacteremia in 6 patients. The median age was highest in the immunological complications compared with infectious complications. Neurological complications occurred mainly in healthy children, while infectious complications, including the invasive bacterial infections were more frequent in patients treated with ibuprofen and/or corticosteroids. The evolution was favorable in most cases. DISCUSSION: The complications of varicella-zoster virus infection occurred mainly in pre-school age and in healthy children. Infectious complications, particularly respiratory complications and bacterial overinfection of the skin and subcutaneous cellular tissue, were the most frequent. There was association between infectious complications and previous therapy with ibuprofen and / or corticosteroids. CONCLUSION: Multicenter studies should be planned in order to optimize and adjust the vaccine strategies to our reality. PMID- 26849760 TI - [Hodgkin's Lymphoma and Autoimmunity: Is There a Relationship?]. AB - INTRODUCTION: The relationship between lymphomas and autoimmune diseases has been reported as bi-directional, however there is a few data in pediatric population. The aim of this work is to evaluate the prevalence of autoimmune diseases in children and adolescents with Hodgkin's lymphoma followed in a Pediatric Oncology Unit. MATERIAL AND METHODS: By reviewing Hodgkin's lymphomas data from the past 16 years (collected prospectively), an apparently large incidence of autoimmune diseases, mostly in female patients, was noted. We decided to do this retrospective study with an update on follow-up. Data analyzed: age, gender, autoimmune disease, temporal relation with lymphoma, lymphoma's stage, histologic subtype and treatment. RESULTS: Fifty-two cases were included, 7 (13.5%) of which, all female, had an autoimmune disease diagnosed previously, simultaneously or after lymphoma. Autoimmune diseases were: juvenile idiopathic arthritis, inflammatory bowel disease, Behcet's disease, autoimmune hepatitis, systemic erythematosus lupus, Hashimoto's thyroiditis and idiopathic thrombocytopenic purpura. The diagnosis was made after lymphoma in 4 patients, before in 2 and simultaneously in 1 patient. All cases, except the one with simultaneous diagnosis, are out of treatment and without oncologic disease relapse. No deaths were registered. DISCUSSION: There was an important prevalence of autoimmune diseases in girls with Hodgkin's lymphoma. We present data and discuss the possible causes based on a literature review. CONCLUSIONS: This relationship should be invoked, requiring more studies, especially in pediatric age. PMID- 26849761 TI - [The Portuguese Guidelines and Patients Values]. AB - INTRODUCTION: Clinical guidelines are support tools, aiming to improve quality of the clinical practice. Patient centered care allows best satisfaction rates, with greater health self-management, and potential gains in quality with fewer costs. OBJECTIVE: To evaluate the integration of patients' values in Portuguese guidelines. MATERIAL AND METHODS: We reviewed the 18 guidelines about cardiovascular diseases published in Portugal from 2011 to 2013, searching for the integration of patients' ideas, fears, expectations and preferences. RESULTS: Eight guidelines were related to diagnosis approach and 10 with treatment. We found references to patients' values in 5 (28%) guidelines, all about treatment aspects. The incorporation of patients' expectations was the most present feature. Reference to financial costs was present in 78% of the guidelines. DISCUSSION: Clinical guidelines are health technology instruments available to practitioners in order to improve the quality of care provided to patients, who are the real users of these tools. As in other countries, there is a tendency to disregard the users' value systems in the conception of the guidelines, giving the privilege to a population logic, not always applicable to the individual, and to financial arithmetic with low support in cost-effectiveness assessments. In the Portuguese case, the way guidelines were proposed conditioned also some suspicion both in the professionals and in the users. CONCLUSION: Portuguese guidelines have low incorporation of references to patients' values. This is more evident when questions about diagnosis are addressed, placing patients in a secondary role in the clinical decision-making process with potential losses in quality of care and eventual increase in costs. PMID- 26849762 TI - [Zika Virus: A Review to Clinicians]. AB - Zika virus is a flavivirus related to Dengue virus, yellow fever virus and West Nile virus. It is considered an emerging arbovirus transmitted by mosquitos of the genus Aedes. Its first description took place in 1947 in the Zika Forest in Uganda, isolated on Rhesus monkey used as bait to study the yellow fever virus. Sporadic cases have been detected in African countries and at the end of the 70's in Indonesia. In 2007, epidemics were described in Micronesia and other islands in the Pacific Ocean and more recently in Brazil. Clinical picture is characterized as a 'dengue-like' syndrome, with abrupt onset of fever and an early onset evanescent rash, often pruritic. Occasionally the disease has been associated with Guillain-Barre syndrome. Nevertheless, until now deaths and complications caused by the disease were not reported. The diagnosis can be performed by PCR or by IgG and IgM antibodies detection. The rapid spread of the virus and its epidemic potential are especially problematic in countries where there are the circulation of other arboviruses which imposes difficulties in the differential diagnosis and healthcare burden. Control measures are the same recommended for dengue and chikungunya which are based in health education and vector control. PMID- 26849763 TI - [Duration of Atrial Fibrillation Episodes and Implications for the Thromboembolic Risk]. AB - INTRODUCTION: Atrial fibrillation is the most common chronic arrhythmia in clinical practice, which is associated with a well known increased thromboembolic risk. The use of oral anticoagulants in this context is well established. However, there are some gaps in information that warrant further studies, such as the duration of an atrial fibrillation event that is long enough to increase the risk of embolic phenomena. This may be of important clinical concern, particularly in patients with cardiac implanted devices, in which very short periods of asymptomatic atrial fibrillation are often detected. MATERIAL AND METHODS: We performed a critical review on the association of brief atrial fibrillation episodes and thromboembolic events, based on available literature indexed on PubMed. RESULTS: After initial selection of abstracts and checking of references a final pool of 8 papers were analysed; seven describing studies with cardiac implanted devices and one with Holter monitoring. Four of the studies addressed this issue with a 'daily burden' approach rather than single episode duration. The risk increases with the magnitude of atrial fibrillation burden, with 5 minutes of atrial fibrillation in one day being the shortest time shown to independently predict thromboembolic events. DISCUSSION: The formation of an intracardiac thrombus, and respective embolic potential, is a dynamic process resulting from the interaction of anatomical and functional variables. The individual risk will depend on these factors. The association between embolic events and short atrial fibrillation episodes is evident, although the mechanism is not obvious, given the time discrepancy that is frequently observed between atrial fibrillation episode and clinical event. CONCLUSIONS: An atrial fibrillation burden of 5 minutes in one day has been shown to be independently associated with a significantly increased risk, although the cause-effect mechanism is not clear. A standardized way to select patients with short-duration atrial fibrillation periods that will have a meaningful benefit of chronic oral anticoagulation is still to define. Therefore, decisions should be made in an individualized manner. PMID- 26849764 TI - [A Rare Case of Neonatal Teeth]. AB - Neonatal teeth is a rare disorder of tooth eruption, arising in the oral cavity, usually in the anterior mandible, in the first month of life. Its etiology is unknown. This condition can cause breastfeeding difficulties, besides aspiration or swallowing of the teeth. We describe the case of a premature infant in the second day of life presented with gingival edema, redness and discrete swelling in the region of the mandibular central incisors. Ten days later, two small teeth with hypermobility were detected. Extraction of those teeth was performed. With this clinical case we intend to show the rarity of this entity, especially in premature infants, the possible association with various syndromes and the need for a multifactorial approach to the treatment decision (extraction / conservative treatment). PMID- 26849765 TI - [Selective Arterial Embolization for a Large Pelvic Aneurysmal Bone Cyst Treatment]. AB - Aneurysmal bone cysts are benign musculoskeletal tumours, which occur in young patients and, occasionally, with aggressive behaviour. Those tumours very often will need surgical treatment with curettage and bone grafting, but for aggressive lesions, inbloc resection is more advisable. Aggressive tumours use to be large and sometimes with difficult surgical approach and demanding complex surgical reconstructions. In this scenario, selective arterial embolization is a possible primary or adjuvant treatment option. This paper presents a paradigmatic case, where selective arterial embolization allowed a successful treatment of a large aneurysmal bone cyst with difficult surgical resolution. PMID- 26849766 TI - A Pink Conjunctival Lesion. PMID- 26849767 TI - [Juvenile Systemic Sclerosis]. PMID- 26849768 TI - [Approach and Registry of Anaphylaxis in Portugal]. AB - Anaphylaxis has a growing incidence, especially in children. It represents a medical emergency and its successful therapy depends on early and proper intervention. Intramuscular epinephrine, with dose adjustment according to weight and age, is the drug of choice for anaphylaxis treatment. After resolution of the acute reaction, the patient should be kept under clinical surveillance for 6 to 24 hours, due to possible biphasic reactions. Prescription of an epinephrine auto injectable device should be considered in all patients with diagnosed or suspected anaphylaxis; additionally these patients should always be referred to an Immunoallergy consultation, to perform adequate investigation and management in order to reduce future risk. All anaphylaxis episodes must be recorded in The Portuguese Catalogue of Allergies and other Adverse Reactions (Catalogo Portugues de Alergias e outras Reacoes Adversas, CPARA), which represents a fundamental tool to share clinical information within the Health System. The present manuscript intends to disclose the most recent Portuguese guidelines for the diagnosis and treatment of anaphylaxis, making its clinical approach more effective and homogeneous, and to promote the use of The Portuguese Catalogue of Allergies and other Adverse Reactions as an essential tool to register and share information on anaphylaxis in Portugal. PMID- 26849769 TI - The Modern Value of Clinical Autopsies. PMID- 26849770 TI - Catalyst-Free Synthesis of Borylated Lactones from Esters via Electrophilic Oxyboration. AB - A catalyst-free oxyboration reaction of alkynes is developed. The resulting borylated isocoumarins and 2-pyrones are isolated as boronic acids, pinacolboronate esters, or potassium organotrifluoroborate salts, providing a variety of bench-stable organoboron building blocks for downstream functionalization. This method has functional group compatibility, is scalable, and proceeds with readily available materials: B-chlorocatecholborane and methyl esters. Mechanistic studies indicate that the B-chlorocatecholborane acts as a carbophilic Lewis acid toward the alkyne, providing a mechanistically distinct pathway for oxyboration that avoids B-O sigma bond formation and enables this catalyst-free route. PMID- 26849771 TI - How the stimulus defines the dynamics of vesicle pool recruitment, fusion mode, and vesicle recycling in neuroendocrine cells. AB - The pattern of stimulation defines important characteristics of the secretory process in neurons and neuroendocrine cells, including the pool of secretory vesicles being recruited, the type and amount of transmitters released, the mode of membrane retrieval, and the mechanisms associated with vesicle replenishment. This review analyzes the mechanisms that regulate these processes in chromaffin cells, as well as in other neuroendocrine and neuronal models. A common factor in these mechanisms is the spatial and temporal distribution of the Ca(2+) signal generated during cell stimulation. For instance, neurosecretory cells and neurons have pools of vesicles with different locations with respect to Ca(2+) channels, and those pools are therefore differentially recruited following different patterns of stimulation. In this regard, a brief stimulus will induce the exocytosis of a small pool of vesicles that is highly coupled to voltage dependent Ca(2+) channels, whereas longer or more intense stimulation will provoke a global Ca(2+) increase, promoting exocytosis irrespective of vesicle location. The pattern of stimulation, and therefore the characteristics of the Ca(2+) signal generated by the stimulus also influence the mode of exocytosis and the type of endocytosis. Indeed, low-frequency stimulation favors kiss-and-run exocytosis and clathrin-independent fast endocytosis, whereas higher frequencies promote full fusion and clathrin-dependent endocytosis. This latter type of endocytosis is accelerated at high-frequency stimulation. Synaptotagmins, calcineurin, dynamin, complexin, and actin remodeling, appear to be involved in the mechanisms that determine the response of these processes to Ca(2+) . In chromaffin cells, a brief stimulus induces the exocytosis of a small pool of vesicles that is highly coupled to voltage-dependent Ca(2+) channels (A), whereas longer or high-frequency stimulation provokes a global Ca(2+) increase, promoting exocytosis irrespective of vesicle location (B). Furthermore, low-frequency stimulation favors kiss-and-run exocytosis (A), whereas higher frequencies promote full fusion (B). In this review, we analyze the mechanisms by which a given stimulation pattern defines the mode of exocytosis, and recruitment and recycling of neurosecretory vesicles. This article is part of a mini review series on Chromaffin cells (ISCCB Meeting, 2015). PMID- 26849774 TI - Duration of therapy of ventilator-associated pneumonia. AB - PURPOSE OF REVIEW: Ventilator-associated pneumonia (VAP) is a major cause of morbidity and mortality in the critical care setting. It incurs great additional cost and the antibiotics prescribed for patients with VAP account for the majority of total antibiotic prescriptions. The increased cost of VAP as well as the emergence of antimicrobial resistance and the potential adverse events because of treatment indicate that the application of shorter antibiotic regimens for the treatment of VAP poses as a one-way choice. RECENT FINDINGS: According to the findings of relevant randomized controlled trials, patients receiving short course regimens for the treatment of VAP have significantly more antibiotic-free days without any negative impact on mortality. Additionally, no other differences were found regarding other secondary outcomes. However, there were higher relapse rates in patients with VAP because of nonfermenting Gram-negative bacilli and there was a lower emergence of multidrug-resistant pathogens. SUMMARY: The shortening of the duration of treatment for VAP is promising, as long as a holistic approach that combines methods ensuring the adequate sterilization of septic foci, the optimization of antibiotic levels, the multifaceted delivery of antimicrobials in the lung and the usage of biomarkers that allow the monitoring of the disease course and the effectiveness of administered treatment are incorporated in clinical practice. PMID- 26849772 TI - Isolates of Alpinia officinarum Hance as COX-2 inhibitors: Evidence from anti inflammatory, antioxidant and molecular docking studies. AB - BACKGROUND: Inflammation triggered by oxidative stress can cause various ailments, such as cancer, rheumatoid arthritis, asthma, diabetes etc. In the last few years, there has been a renewed interest in studying the antioxidant and anti inflammatory action of plant constituents such as flavonoids and diarylheptanoids. AIM: To evaluate the antioxidant, anti-inflammatory activity and the total phenolic content of isolated compounds from Alpinia officinarum rhizomes. Furthermore, molecular docking was performed to study the binding mode of these compounds into the active site of cyclooxygenase-2 (COX-2). METHODS: A. officinarum rhizomes were extracted by maceration, using methanol. This extract was further fractionated by partitioning with hexane, chloroform and ethyl acetate and these fractions on further purification resulted in isolation of five pure compounds. Characterization was carried out by using (1)H NMR, (13)C NMR and MS. They were further evaluated for antioxidant and anti-inflammatory activity using carrageenan-induced paw edema model in rats. Molecular docking study was performed using Glide module integrated in Schrodinger molecular modeling software. RESULTS: The compounds were identified as 1,7-diphenylhept-4-en-3-one (1), 5-hydroxy-1,7-diphenyl-3-heptanone (2), 3,5,7-trihydroxyflavone (Galangin, 3), 3,5,7-trihydroxy-4'-methoxyflavone (Kaempferide, 4) and 5-hydroxy-7-(4" hydroxy-3"-methoxyphenyl)-1-phenyl-3-heptanone (5). The compound-3 and compound-5 (10mg/kg) showed significant (p<0.001) antioxidant and anti-inflammatory potential. Moreover, total phenolic content was detected as 72.96 mg and 51.18 mg gallic acid equivalent respectively. All the five isolates were found to be good binders with COX-2 (average docking score -9.03). CONCLUSIONS: Galangin and 5 hydroxy-7-(4"-hydroxy-3"-methoxyphenyl)-1-phenyl-3-heptanone exhibited anti inflammatory and in-vitro antioxidant activity which may be due to presence of phenolic content in it. The molecular docking study revealed that these compounds have affinity towards COX-2 active site which can further be explored as selective COX-2 inhibitors. The results obtained in this work justify the use of A. officinarum in the treatment of inflammatory disorders like rheumatoid arthritis and inflammatory bowel diseases. PMID- 26849776 TI - A 250 mV Cu/SiO2/W Memristor with Half-Integer Quantum Conductance States. AB - Memristive devices, whose conductance depends on previous programming history, are of significant interest for building nonvolatile memory and brain-inspired computing systems. Here, we report half-integer quantized conductance transitions G = (n/2) (2e(2)/h) for n = 1, 2, 3, etc., in Cu/SiO2/W memristive devices observed below 300 mV at room temperature. This is attributed to the nanoscale filamentary nature of Cu conductance pathways formed inside SiO2. Retention measurements also show spontaneous filament decay with quantized conductance levels. Numerical simulations shed light into the dynamics underlying the data retention loss mechanisms and provide new insights into the nanoscale physics of memristive devices and trade-offs involved in engineering them for computational applications. PMID- 26849775 TI - Use of the Salmonella MgtR peptide as an antagonist of the Mycobacterium MgtC virulence factor. AB - BACKGROUND: The MgtC virulence factor has been proposed as an attractive target for antivirulence strategies because it is shared by several important bacterial pathogens, including Salmonella enterica and Mycobacterium tuberculosis (Mtb). AIM: A natural antagonistic peptide, MgtR, which interacts with MgtC and modulates its stability, has been identified in Salmonella, and we investigated its efficiency to target MgtC in another pathogen. MATERIALS & METHODS: We evaluated the interaction between Salmonella MgtR peptide and the Mtb MgtC protein using an in vivo bacterial two-hybrid system and we addressed the effect of exogenously added synthetic MgtR and endogenously expressed peptide. RESULTS: MgtR peptide strongly interacted with Mtb MgtC protein and exogenously added synthetic MgtR peptide-reduced Mtb MgtC level and interfered with the dimerization of Mtb MgtC. Importantly, heterologous expression of MgtR in Mycobacterium bovis BCG resulted in increased phagocytosis and reduced intramacrophage survival. CONCLUSION: MgtR peptide can target Mtb MgtC protein and reduce mycobacterial macrophage resistance, thus providing a promising new scaffold for the development of antivirulence compounds. PMID- 26849777 TI - Application of Plasma Levels of Olanzapine and N-Desmethyl-Olanzapine to Monitor Clinical Efficacy in Patients with Schizophrenia. AB - BACKGROUND: This therapeutic drug monitoring (TDM) study aimed to determine the role of olanzapine (OLZ) and N-desmethyl-OLZ (DMO) levels in the therapeutic efficacy of OLZ in patients with schizophrenia. METHOD: Plasma concentrations of OLZ (COLZ) and DMO (CDMO) in schizophrenic patients 12 hours post-dose were assessed. The correlations of COLZ and CDMO with the various scores of the Positive and Negative Syndrome Scale (PANSS) were evaluated. A receiver operating characteristic curve (ROC) was utilized to identify the threshold COLZ and COLZ/CDMO ratio for maintenance of satisfactory efficacy. RESULTS: A total of 151 samples from patients with schizophrenia were analyzed for individual COLZ and CDMO levels. The mean COLZ and CDMO levels were 37.0 +/- 25.6 and 6.9 +/- 4.7 ng/mL, respectively, and COLZ was ~50% higher in female or nonsmokers (p<0.01). In all patients, the daily dose of OLZ was positively correlated with COLZ and CDMO. Linear relationships between COLZ and OLZ dose were observed in both nonsmokers and smokers (rs = 0.306, 0.426, p<0.01), although CDMO was only correlated with OLZ dose in smokers (rs = 0.485, p<0.01) and not nonsmokers. In all patients, COLZ was marginally negatively correlated with the total PANSS score. The total PANSS score was significantly negatively correlated with the COLZ/CDMO ratio (p<0.005), except in smokers. The ROC analysis identified a COLZ/CDMO ratio >=2.99 or COLZ >=22.77 ng/mL as a predictor of maintenance of an at least mildly ill status (PANSS score <=58) of schizophrenia in all patients. CONCLUSIONS: A significantly negative correlation between the steady-state COLZ/CDMO ratio and total PANSS score was observed in Taiwanese schizophrenic patients. TDM of both OLZ and DMO levels could assist clinical practice when individualizing OLZ dosage adjustments for patients with schizophrenia. PMID- 26849778 TI - Thiazolino 2-Pyridone Amide Inhibitors of Chlamydia trachomatis Infectivity. AB - The bacterial pathogen Chlamydia trachomatis is a global health burden currently treated with broad-spectrum antibiotics which disrupt commensal bacteria. We recently identified a compound through phenotypic screening that blocked infectivity of this intracellular pathogen without host cell toxicity (compound 1, KSK 120). Herein, we present the optimization of 1 to a class of thiazolino 2 pyridone amides that are highly efficacious (EC50 <= 100 nM) in attenuating infectivity across multiple serovars of C. trachomatis without host cell toxicity. The lead compound 21a exhibits reduced lipophilicity versus 1 and did not affect the growth or viability of representative commensal flora at 50 MUM. In microscopy studies, a highly active fluorescent analogue 37 localized inside the parasitiphorous inclusion, indicative of a specific targeting of bacterial components. In summary, we present a class of small molecules to enable the development of specific treatments for C. trachomatis. PMID- 26849779 TI - Accuracy and Reliability of Internet Resources for Information on Idiopathic Pulmonary Fibrosis. AB - RATIONALE: Patients commonly use the Internet as a resource for health information; however, no studies have evaluated the online information about idiopathic pulmonary fibrosis (IPF). OBJECTIVES: We sought to determine the readability, content (compared with established guidelines), bias, and quality of online IPF resources. METHODS: We analyzed the first 200 hits for "idiopathic pulmonary fibrosis" in Google, Yahoo, and Bing. Each website was evaluated for content related to IPF features and treatments that are discussed in clinical guidelines. Website quality was assessed using the validated DISCERN instrument. MEASUREMENTS AND MAIN RESULTS: Eligibility criteria were met in 181 websites. The median reading grade level was 12. More content was provided in scientific resources (academic institutions or governmental organizations) and foundation/advocacy organization sites than in personal commentary (blog) sites; however, most sites provided incomplete and/or inaccurate information. Nonindicated and/or harmful pharmacotherapies for IPF were described as potential IPF treatments in 48% of websites and were most often recommended in foundation/advocacy organization websites. Azathioprine and corticosteroids were discussed as potential chronic treatments of IPF in 13.3 and 30.6% of the 98 websites that had been updated after publication of data demonstrating harm from these medications. Website quality (DISCERN score) was poor in all site types but was worse in news/media reports and personal commentary (blog) sites than in sites from scientific and foundation/advocacy organizations. CONCLUSIONS: Patient directed online information on IPF is frequently incomplete, inaccurate, and outdated. There is no reliable method for patients to identify sites that provide appropriate information on IPF. PMID- 26849782 TI - An expert system for the quantification of fault rates in construction fall accidents. AB - INTRODUCTION: Expert witness reports, prepared with the aim of quantifying fault rates among parties, play an important role in a court's final decision. However, conflicting fault rates assigned by different expert witness boards lead to iterative objections raised by the related parties. This unfavorable situation mainly originates due to the subjectivity of expert judgments and unavailability of objective information about the causes of accidents. As a solution to this shortcoming, an expert system based on a rule-based system was developed for the quantification of fault rates in construction fall accidents. The aim of developing DsSafe is decreasing the subjectivity inherent in expert witness reports. METHODOLOGY: Eighty-four inspection reports prepared by the official and authorized inspectors were examined and root causes of construction fall accidents in Turkey were identified. Using this information, an evaluation form was designed and submitted to the experts. Experts were asked to evaluate the importance level of the factors that govern fall accidents and determine the fault rates under different scenarios. Based on expert judgments, a rule-based expert system was developed. The accuracy and reliability of DsSafe were tested with real data as obtained from finalized court cases. RESULT: DsSafe gives satisfactory results. PMID- 26849781 TI - Estimation of sparse directed acyclic graphs for multivariate counts data. AB - The next-generation sequencing data, called high-throughput sequencing data, are recorded as count data, which are generally far from normal distribution. Under the assumption that the count data follow the Poisson log-normal distribution, this article provides an L1-penalized likelihood framework and an efficient search algorithm to estimate the structure of sparse directed acyclic graphs (DAGs) for multivariate counts data. In searching for the solution, we use iterative optimization procedures to estimate the adjacency matrix and the variance matrix of the latent variables. The simulation result shows that our proposed method outperforms the approach which assumes multivariate normal distributions, and the log-transformation approach. It also shows that the proposed method outperforms the rank-based PC method under sparse network or hub network structures. As a real data example, we demonstrate the efficiency of the proposed method in estimating the gene regulatory networks of the ovarian cancer study. PMID- 26849783 TI - Lower Body Stiffness Modulation Strategies in Well Trained Female Athletes. AB - Millett, EL, Moresi, MP, Watsford, ML, Taylor, PG, and Greene, DA. Lower body stiffness modulation strategies in well trained female athletes. J Strength Cond Res 30(10): 2845-2856, 2016-Lower extremity stiffness quantifies the relationship between the amount of leg compression and the external load to which the limb are subjected. This study aimed to assess differences in leg and joint stiffness and the subsequent kinematic and kinetic control mechanisms between athletes from various training backgrounds. Forty-seven female participants (20 nationally identified netballers, 13 high level endurance athletes and 14 age and gender matched controls) completed a maximal unilateral countermovement jump, drop jump and horizontal jump to assess stiffness. Leg stiffness, joint stiffness and associated mechanical parameters were assessed with a 10 camera motion analysis system and force plate. No significant differences were evident for leg stiffness measures between athletic groups for any of the tasks (p = 0.321-0.849). However, differences in joint stiffness and its contribution to leg stiffness, jump performance outcome measures and stiffness control mechanisms were evident between all groups. Practitioners should consider the appropriateness of the task utilised in leg stiffness screening. Inclusion of mechanistic and/or more sports specific tasks may be more appropriate for athletic groups. PMID- 26849784 TI - The Effect of beta-Hydroxy-beta-Methylbutyrate on Aerobic Capacity and Body Composition in Trained Athletes. AB - Durkalec-Michalski, K and Jeszka, J. The effect of beta-hydroxy-beta methylbutyrate on aerobic capacity and body composition in trained athletes. J Strength Cond Res 30(9): 2617-2626, 2016-The aim of this study was to investigate whether supplementation with beta-hydroxy-beta-methylbutyrate (HMB) affects body composition, aerobic capacity, or intramuscular enzymes activity, as well as in anabolic and/or catabolic hormones and lactate concentrations. A cohort of 58 highly trained males was subjected to 12-week supplementation with HMB (3 * 1 gHMB.d) and a placebo (PLA) in randomized, PLA controlled, double-blind crossover trials, with a 10-day washout period. Body composition and aerobic capacity were recorded, whereas the levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol, and lactate, as well as the T/C ratio, in blood samples were measured. After HMB supplementation, fat-free mass increased (+0.2 kgHMB vs. -1.0 kgPLA, p = 0.021), with a simultaneous reduction of fat mass (-0.8 kgHMB vs. +0.8 kgPLA, p < 0.001). In turn, after HMB supplementation, in comparison to PLA, maximal oxygen uptake (V[Combining Dot Above][Combining Dot Above]O2max: +0.102 L.minHMB vs. -0.063 L.minPLA, p = 0.013), time to reach ventilatory threshold (VT) (TVT: +1.0 minHMB vs. -0.4 minPLA, p < 0.0001), threshold load at VT (WVT: +20 WHMB vs. -7 WPLA, p = 0.001), and the threshold heart rate at VT (HRVT: +8 b.minHMB vs. -1 b.minPLA, p < 0.0001) increased significantly. Analysis of the tested biochemical markers shows significant differences only in relation to the initial concentration. In HMB group, testosterone levels increased (p = 0.047) and in both groups (HMB: p = 0.008; PLA: p = 0.008) higher cortisol levels were observed. The results indicate that supplying HMB promotes advantageous changes in body composition and stimulates an increase in aerobic capacity, although seeming not to significantly affect the levels of the analyzed blood markers. PMID- 26849786 TI - External Responsiveness and Intrasession Reliability of the Rope-Climbing Test. AB - Dhahbi, W, Chamari, K, Cheze, L, Behm, DG, and Chaouachi, A. External responsiveness and intrasession reliability of the rope-climbing test. J Strength Cond Res 30(10): 2952-2958, 2016-Although the rope-climbing test (RCT) has been validated for upper-body power assessment of Commando soldiers, the external responsiveness and intrasession reliability of the RCT have not been reported. To examine RCT external responsiveness and intrasession reliability, this study consisted of 2 separate phases. Forty male soldiers belonging to the special units of the National Guard, selected on the basis of their training and specialty operations levels, participated in the first phase of the study to identify the discriminant ability of RCT. This group was then divided into anti terrorism Commandos (21 soldiers) and Intervention-Brigade (19 soldiers). Only the anti-terrorism Commandos participated in the intrasession reliability study. The Commandos were significantly better than the Intervention-Brigade soldiers on execution time (ET), absolute power output (APO), and relative power output (RPO; p < 0.001). The areas under the receiver operator characteristics curves were all higher than 0.70: 0.91, 0.85, and 0.90 for ET, APO, and RPO, respectively. The RCT provided good external responsiveness; thus, RCT was considered to indicate "good" discriminative ability. No significant difference was found between groups in posttest rating of perceived exertion. The intrasession reliability coefficients were excellent for ET, APO, and RPO (intraclass correlation coefficient [3,1] > 0.90). The standard errors of measurement values for the ET, APO, and RPO were all less than 5% (range: 1.29-1.47%). The main findings of this study suggest that RCT is a tool with both high sensitivity and intrasession reliability, allowing the consistent detection of differences in upper-limb power performance between the 2 military groups of different operational capacity levels. PMID- 26849785 TI - Determinants of Club Head Speed in PGA Professional Golfers. AB - Turner, AN. Determinants of club head speed in PGA professional golfers. J Strength Cond Res 30(8): 2266-2270, 2016-Club head speed (CHS) has been significantly correlated with golf performance, but only in amateurs. The purpose of this study therefore, was to investigate the relationship between field-based measures of strength and power with CHS in Professional Golfers Association (PGA) professional golfers, and further determine differences between age groups. A correlation design was used to test relationships between squat jump (SJ), seated medicine ball throw (SMBT), rotational medicine ball throw (RMBT), and CHS. Twenty participants volunteered to take part in the study (age, 31.95 +/- 8.7 years; height, 182.75 +/- 6.88 cm; mass, 90.47 +/- 15.6 kg). Intraclass correlation coefficients reported high reliability for performance variables (r = 0.85-0.95). Significant correlations (p < 0.01) were found between CHS and SJ (r = 0.817) and SMBT (r = 0.706), but not RMBT (r = 0.572). A stepwise linear regression analysis identified that SJ and SMBT explained 74% of the variance in CHS. When dividing the sample based on age, professionals <30 years (n = 10; 25.6 +/- 2.9 years) displayed significantly (p <= 0.05) higher CHS and SJ height compared with professionals >30 (n = 10; 39.7 +/- 5.5 years). Correlations to CHS for <30 were significant for SJ (r = 0.801) and SMBT (r = 0.643), but nonsignificant for RMBT. Those >30 had significant correlations to CHS not only in SMBT (r = 0.881) and SJ (r = 0.729), but also in RMBT (r = 0.642). The results of this study suggest that SJ and SMBT have the largest contribution to CHS in PGA professional golfers. When comparing age groups, it appears that younger golfers (<30 years) utilize more leg strength whereas older golfers (>30 years) utilize more upper body strength. Results suggest that strength-based leg exercises and power-based chest exercises may improve CHS in professional golfers. PMID- 26849787 TI - The V[Combining Dot Above]O2 Kinetics of Maximal and Supramaximal Running Exercises in Sprinters and Middle-Distance Runners. AB - do Nascimento Salvador, PC, Dal Pupo, J, De Lucas, RD, de Aguiar, RA, Arins, FB, and Guglielmo, LGA. The V[Combining Dot Above]O2 kinetics of maximal and supramaximal running exercises in sprinters and middle-distance runners. J Strength Cond Res 30(10): 2857-2863, 2016-The aim of this study was to compare the V[Combining Dot Above]O2 kinetics parameters during maximal and supramaximal running exercises in sprinters (SPR) and middle-distance runners (MDR). Twelve SPR (age 20.6 +/- 3.4 years; and body mass 74.9 +/- 6.2 kg) and 10 MDR (age 17.6 +/- 1.4 years; and body mass 70.1 +/- 11.8 kg) performed, on different days, a maximal incremental running test for determination of the velocity at maximum oxygen uptake (vV[Combining Dot Above]O2max) and 2 constant-speed tests for analysis of V[Combining Dot Above]O2 kinetics at 100 and 120% of vV[Combining Dot Above]O2max. The MDR presented significantly higher values for the critical speed (18.0 +/- 1.0 vs. 14.2 +/- 1.0 km.h), vV[Combining Dot Above]O2max (19.4 +/- 0.7 vs. 17.2 +/- 0.8 km.h), and time to exhaustion at 100% (437 +/- 53 vs. 366 +/- 49 seconds) than the SPR (p <= 0.05). However, the SPR demonstrated greater values for the anaerobic distance capacity (281.3 +/- 66.1 vs. 208.0 +/- 43.4 m). Although the mean response time and the time to attain the V[Combining Dot Above]O2max of the V[Combining Dot Above]O2 kinetics was higher in the maximal than supramaximal running speed (p <= 0.05), no difference was found in these parameters as well for V[Combining Dot Above]O2 slow component (p > 0.05) between the groups. This study showed that different aerobic and anaerobic characteristics in MDR and SPR did not affect the V[Combining Dot Above]O2 kinetics in maximal and supramaximal intensities within the severe-intensity domain. From a practical perspective, parameters of V[Combining Dot Above]O2 response may provide helpful information for training control as the duration of stimulus close to V[Combining Dot Above]O2max. PMID- 26849788 TI - Analysis of Agreement Between 4 Lactate Threshold Measurements Methods in Professional Soccer Players. AB - Cerda-Kohler, H, Burgos-Jara, C, Ramirez-Campillo, R, Valdes-Cerda, B, Baez, E, Zapata-Gomez, D, Cristobal Andrade, D, and Izquierdo, M. Analysis of agreement between 4 lactate threshold measurements methods in professional soccer players. J Strength Cond Res 30(10): 2864-2870, 2016-Lactate threshold (LT) represents the inflection point of blood lactate values from rest to high-intensity exercise during an incremental test, is commonly used to determine exercise intensity, and is related to different positional roles of elite soccer players. Different methodologies have been adopted to determine the LT; however, the agreement between these methodologies in professional soccer players is unclear. Seventeen professional soccer players were recruited (age 24.7 +/- 3.7 years, body mass 70.1 +/- 5.3 kg, height 172.8 +/- 7.3 cm) and performed an incremental treadmill test until volitional fatigue. Speed at LT (LTspeed), heart rate at LT (LTHR), and lactate values from capillary blood samples obtained at 3-minute intervals were analyzed using 4 LT measurement methods: visual inspection (VI), maximum distance (Dmax), modified Dmax (DmaxM), and logarithmic (log-log). Only Bland Altman analysis for LTHR showed agreement between VI and Dmax, between VI and DmaxM, and between Dmax and DmaxM methods. No agreement between methods was observed after intraclass correlation coefficient and 95% one-sided lower-limit analysis. Comparative results showed that LTspeed was lower (p < 0.01) with the log-log method compared with the Dmax method and lower (p < 0.01) with the latter compared with the VI and DmaxM methods. Regarding LTHR, higher (p < 0.01) values were observed using the VI, DmaxM, and Dmax methods compared with the log-log method. Therefore, VI, Dmax, DmaxM, and log-log methods should not be used interchangeably for LT measurement. More studies are needed to determine a gold standard for LT detection in professional soccer players. PMID- 26849789 TI - Testing of Badminton-Specific Endurance. AB - Madsen, CM, Hojlyng, M, and Nybo, L. Testing of badminton-specific endurance. J Strength Cond Res 30(9): 2582-2590, 2016-In the present study, a novel intermittent badminton endurance (B-ENDURANCE) test was developed and tested in elite (n = 17) and skilled (n = 9) badminton players and in age-matched physically active men (nonbadminton players; n = 8). In addition, B-ENDURANCE test-retest reproducibility was evaluated in 9 badminton players. The B-ENDURANCE test is an incremental test where each level consists of repeated sequences of badminton-specific actions toward the 4 corners of the court. The subject starts in the center of the court in front of a computer screen and within each sequence, he must, in a randomized order, complete 8 actions as dictated by the computer, providing the audiovisual input and verifying that the appropriate sensor is activated within the allocated time. Recovery time between each sequence is 10 seconds throughout the test, but the time to complete each sequence is gradually decreased until the subjects cannot follow the dictated tempo. The B-ENDURANCE test performance for elite players was better (p <= 0.05) compared with the skilled players and nonbadminton players. In addition, the B ENDURANCE test performance correlated (r = 0.8 and p < 0.0001) with elite players' national single rankings. Test-retest coefficient of variation was 7.9% between the first 2 trials (i.e., without a familiarization trial) but reduced to 2.5% when comparing the second and third trials. In conclusion, the B-ENDURANCE test is relevant for the evaluation of badminton-specific endurance but at least 1 familiarization trial is recommended if the test is used for evaluation of longitudinal changes, e.g., tracking training effects. PMID- 26849587 TI - Study of B Meson Production in p+Pb Collisions at ?[S(NN)]=5.02 TeV Using Exclusive Hadronic Decays. AB - The production cross sections of the B^{+}, B^{0}, and B_{s}^{0} mesons, and of their charge conjugates, are measured via exclusive hadronic decays in p+Pb collisions at the center-of-mass energy sqrt[s_{NN}]=5.02 TeV with the CMS detector at the CERN LHC. The data set used for this analysis corresponds to an integrated luminosity of 34.6 nb^{-1}. The production cross sections are measured in the transverse momentum range between 10 and 60 GeV/c. No significant modification is observed compared to proton-proton perturbative QCD calculations scaled by the number of incoherent nucleon-nucleon collisions. These results provide a baseline for the study of in-medium b quark energy loss in Pb+Pb collisions. PMID- 26849790 TI - Comparison of Sodium Chloride Tablets-Induced, Sodium Chloride Solution-Induced, and Glycerol-Induced Hyperhydration on Fluid Balance Responses in Healthy Men. AB - Savoie, FA, Asselin, A, and Goulet, EDB. Comparison of sodium chloride tablets induced, sodium chloride solution-induced, and glycerol-induced hyperhydration on fluid balance responses in healthy men. J Strength Cond Res 30(10): 2880-2891, 2016-Sodium chloride solution-induced hyperhydration (NaCl-SolIH) is a powerful strategy to increase body water before exercise. However, NaCl-SolIH is associated with an unpleasant salty taste, potentially dissuading some athletes from using it and coaches from recommending it. Therefore, we evaluated the hyperhydrating potential of sodium chloride tablets-induced hyperhydration (NaCl TabIH), which bypasses the palatability issue of NaCl-SolIH without sacrificing sodium chloride content, and compared it to NaCl-SolIH and glycerol-induced hyperhydration (GIH). Sixteen healthy males (age: 21 +/- 2 years; fat-free mass (FFM): 65 +/- 6 kg) underwent three, 3-hour long passive hyperhydration protocols during which they drank, over the first 60 minutes, 30-ml.kg FFM of an artificially sweetened solution. During NaCl-TabIH, participants swallowed 7.5, 1 g each, sodium chloride tablets with every liter of solution. During NaCl-SolIH, an equal quantity of sodium chloride tablets was dissolved in each liter of solution. With GIH, the glycerol concentration was 46.7 g.L. Urine production, fluid retention, hemoglobin, hematocrit, plasma volume, and perceptual variables were monitored throughout the trials. Total fluid intake was 1948 +/- 182 ml. After 3 hour, there were no significant differences among treatments for hemoglobin, hematocrit, and plasma volume changes. Fluid retention was significantly greater with NaCl-SolIH (1150 +/- 287 ml) than NaCl-TabIH (905 +/- 340 ml) or GIH (800 +/- 211 ml), with no difference between NaCl-TabIH and GIH. No differences were found among treatments for perceptual variables. NaCl-TabIH and GIH are equally effective, but inferior than NaCl-SolIH. NaCl-TabIH represents an alternative to hyperhydration induced with glycerol, which is prohibited by the World Anti-Doping Agency. PMID- 26849791 TI - Effects of Short-Interval and Long-Interval Swimming Protocols on Performance, Aerobic Adaptations, and Technical Parameters: A Training Study. AB - Dalamitros, AA, Zafeiridis, AS, Toubekis, AG, Tsalis, GA, Pelarigo, JG, Manou, V, and Kellis, S. Effects of short-interval and long-interval swimming protocols on performance, aerobic adaptations, and technical parameters: A training study. J Strength Cond Res 30(10): 2871-2879, 2016-This study compared 2-interval swimming training programs of different work interval durations, matched for total distance and exercise intensity, on swimming performance, aerobic adaptations, and technical parameters. Twenty-four former swimmers were equally divided to short-interval training group (INT50, 12-16 * 50 m with 15 seconds rest), long interval training group (INT100, 6-8 * 100 m with 30 seconds rest), and a control group (CON). The 2 experimental groups followed the specified swimming training program for 8 weeks. Before and after training, swimming performance, technical parameters, and indices of aerobic adaptations were assessed. IotaNuTau50 and IotaNuTau100 improved swimming performance in 100 and 400-m tests and the maximal aerobic speed (p <= 0.05); the performance in the 50-m swim did not change. Posttraining V[Combining Dot Above]O2max values were higher compared with pretraining values in both training groups (p <= 0.05), whereas peak aerobic power output increased only in INT100 (p <= 0.05). The 1-minute heart rate and blood lactate recovery values decreased after training in both groups (p < 0.01). Stroke length increased in 100 and 400-m swimming tests after training in both groups (p <= 0.05); no changes were observed in stroke rate after training. Comparisons between groups on posttraining mean values, after adjusting for pretraining values, revealed no significant differences between IotaNuTau50 and IotaNuTau100 for all variables; however, all measures were improved vs. the respective values in the CON (p < 0.001-0.05). In conclusion, when matched for distance and exercise intensity, the short-interval (50 m) and long-interval (100 m) protocols confer analogous improvements in swimming performance, in stroke cycle parameters, and in indices of aerobic adaptations after 8 weeks of training. PMID- 26849795 TI - Kinetics and Mechanism of the Chlorite-Periodate System: Formation of a Short Lived Key Intermediate OClOIO3 and Its Subsequent Reactions. AB - The chlorite-periodate reaction has been studied spectrophotometrically in acidic medium at 25.0 +/- 0.1 degrees C, monitoring the absorbance at 400 nm in acetate/acetic acid buffer at constant ionic strength (I = 0.5 M). We have shown that periodate was exclusively reduced to iodate, but chlorite ion was oxidized to chlorate and chlorine dioxide via branching pathways. The stoichiometry of the reaction can be described as a linear combination of two limiting stoichiometries under our experimental conditions. Detailed initial rate studies have clearly revealed that the formal kinetic orders of hydrogen ion, chlorite ion, and periodate ion are all strictly one, establishing an empirical rate law to be d[ClO2]/dt = kobs[ClO2(-)][IO4(-)][H(+)], where the apparent rate coefficient (kobs) was found to be 70 +/- 13 M(-2) s(-1). On the basis of the experiments, a simple four-step kinetic model with three fitted kinetic parameters is proposed by nonlinear parameter estimation. The reaction was found to proceed via a parallel oxygen transfer reaction leading to the exclusive formation of chlorate and iodate as well as via the formation of a short-lived key intermediate OClOIO3 followed by its further transformations by a sequence of branching pathways. PMID- 26849792 TI - Utilization of Practice Session Average Inertial Load to Quantify College Football Injury Risk. AB - Wilkerson, GB, Gupta, A, Allen, JR, Keith, CM, and Colston, MA. Utilization of practice session average inertial load to quantify college football injury risk. J Strength Cond Res 30(9): 2369-2374, 2016-Relatively few studies have investigated the potential injury prevention value of data derived from recently developed wearable technology for measurement of body mass accelerations during the performance of sport-related activities. The available evidence has been derived from studies focused on avoidance of overtraining syndrome, which is believed to induce a chronically fatigued state that can be identified through monitoring of inertial load accumulation. Reduced variability in movement patterns is also believed to be an important injury risk factor, but no evidence currently exists to guide interpretation of data derived from inertial measurement units (IMUs) in this regard. We retrospectively analyzed archived data for a cohort of 45 National Collegiate Athletic Association Division 1 football bowl subdivision football players who wore IMUs on the upper back during practice sessions to quantify any associations between average inertial load measured during practice sessions and occurrence of musculoskeletal sprains and strains. Both the coefficient of variation for average inertial load and frequent exposure to game conditions were found to be strongly associated with injury occurrence. Having either or both of the 2 risk factors provided strong discrimination between injured and noninjured players (chi = 9.048; p = 0.004; odds ratio = 8.04; 90% CI: 2.39, 27.03). Our findings may facilitate identification of individual football players who are likely to derive the greatest benefit from training activities designed to reduce injury risk through improved adaptability to rapidly changing environmental demands. PMID- 26849793 TI - Whole Body Vibration Immediately Decreases Lower Extremity Loading During the Drop Jump. AB - Chen, Z-R, Peng, H-T, Siao, S-W, Hou, Y-T, and Wang, L-I. Whole body vibration immediately decreases lower extremity loading during the drop jump. J Strength Cond Res 30(9): 2476-2481, 2016-The purpose of this study was to evaluate the acute effect of whole body vibration (WBV) on lower extremity loading during the drop jump (DJ). Fifteen male collegiate physical education students randomly completed 3 experimental sessions on 3 separate days with 4 days interval between sessions (performing 3 trials of DJ from 30-, 40-, and 50-cm drop heights before WBV and 4 minutes after WBV). Eight cameras and 2 force platforms were used to record kinematic and kinetic data, respectively. Peak impact force and loading rate significantly decreased after WBV during DJ from 40 and 50 cm. Knee angular displacements significantly increased after WBV during DJ from 30, 40, and 50 cm. Whole body vibration may help immediately reduce lower extremity loading. PMID- 26849794 TI - Five Weeks of Sprint and High-Intensity Interval Training Improves Paddling Performance in Adolescent Surfers. AB - Farley, ORL, Secomb, JL, Parsonage, JR, Lundgren, LE, Abbiss, CR, and Sheppard, JM. Five weeks of sprint and high-intensity interval training improves paddling performance in adolescent surfers. J Strength Cond Res 30(9): 2446-2452, 2016-The purpose of our study was to examine the effects of sprint interval training (SIT; 10 seconds) and high-intensity interval training (HIT; 30 seconds) on surfing athletes paddling performance (400-m time trial and repeat-sprint paddle performance). Twenty-four competitive adolescent surfers (19 male, 5 female; age = 14.4 +/- 1.3 years, mass: 50.1 +/- 10.7 kg, and stature: 159.9 +/- 10.3 cm) were assigned to perform either 5 weeks of SIT and HIT. Participants completed a repeated-sprint paddle ability test (RSPT, 15-m surfboard sprint paddle initiated every 40 seconds * 10 bouts) and 400-m endurance surfboard paddle time trial before and after training. High-intensity interval training decreased the total time to complete the 400 m by 15.8 +/- 16.1 seconds (p = 0.03), and SIT decreased the total time to complete the RSPT by 6.5 +/- 4.3 seconds (p = 0.02). Fatigue index during the RSPT (first-slowest effort) was lower after HIT and SIT (p <= 0.001 and p = 0.02, respectively). There were no significant differences in performance changes in the 400 m (total time) and RSPT (total time, fastest 15 m time, and peak velocity) between HIT and SIT. Our study indicates that HIT and SIT may be implemented to the training program of surfers to improve aerobic and repeat-sprint paddle ability, both of which are identified as key aspects of the sport. In addition, these findings indicate that 400-m paddle and RSPT can discriminate between aerobic and anaerobic training adaptations, with aerobic gains likely from HIT and anaerobic gains from SIT. PMID- 26849796 TI - Optical Coherence Tomographic Elastography Reveals Mesoscale Shear Strain Inhomogeneities in the Annulus Fibrosus. AB - STUDY DESIGN: Basic science study using in vitro tissue testing and imaging to characterize local strains in annulus fibrosus (AF) tissue. OBJECTIVE: To characterize mesoscale strain inhomogeneities between lamellar and inter /translamellar (ITL) matrix compartments during tissue shear loading. SUMMARY OF BACKGROUND DATA: The intervertebral disc is characterized by significant heterogeneities in tissue structure and plays a critical role in load distribution and force transmission in the spine. In particular, the AF possesses a lamellar architecture interdigitated by a complex network of extracellular matrix components that form a distinct ITL compartment. Currently, there is not a firm understanding of how the lamellar and ITL matrix coordinately support tissue loading. METHODS: AF tissue samples were prepared from frozen porcine lumbar spines and mounted onto custom fixtures of a materials testing system that incorporates optical coherence tomography (OCT) imaging to perform tissue elastography. Tissues were subjected to 20 and 40% nominal shear strain, and OCT images were captured and segmented to identify regions of interest corresponding to lamellar and ITL compartments. Images were analyzed using an optical flow algorithm to quantify local shear strains within each compartment. RESULTS: Using histology and OCT, we first verified our ability to visualize and discriminate the ITL matrix from the lamellar matrix in porcine AF tissues. Local AF strains in the ITL compartment (22.0 +/- 13.8, 31.1 +/- 16.9 at 20% and 40% applied shear, respectively) were significantly higher than corresponding strains in the surrounding lamellar compartment (12.1 +/- 5.6, 15.3 +/- 5.2) for all tissue samples (P < 0.05). CONCLUSION: Results from this study demonstrate that the lamellar and ITL compartments of the AF distribute strain unevenly during tissue loading. Specifically, shear strain is significantly higher in the ITL matrix, suggesting that these regions may be more susceptible to tissue damage and more mechanobiologically active. LEVEL OF EVIDENCE: N/A. PMID- 26849798 TI - Allene Functionalized Azobenzene Linker Enables Rapid and Light-Responsive Peptide Macrocyclization. AB - In this manuscript, we describe the efficient synthesis of a bis(allenamide) functionalized water-soluble azobenzene reagent (BSBDA) and its application as a new tool for the rapid generation of visible light-responsive macrocyclic peptides and peptide libraries displayed on the surface of bacteriophage. The allenamide functionality promotes cysteine ligation in model peptides and those displayed on phage with rates 2-3 orders of magnitude faster than the established alkyl halide containing azobenzenes. PMID- 26849797 TI - Hyperferritinemia-cataract syndrome: Long-term ophthalmic observations in an Italian family. AB - BACKGROUND: Hyperferritinemia-cataract syndrome (HCS) is a rare Mendelian condition characterized by bilateral cataract and high levels of serum ferritin in the absence of iron overload. METHODS: HCS was diagnosed in three adult siblings. In two of them it was possible to assess lens changes initially in 1995 and again in 2013. Serum ferritin, iron, transferrin concentrations and transferrin saturation percentage were also measured, and the Iron Responsive Element (IRE) region of the L-ferritin gene (FTL) was studied. RESULTS: Serum ferritin concentrations were considerably elevated while serum iron, transferrin and transferrin saturation levels were within the normal range in each sibling. Cataract changes in our patients were consistent with those previously reported in the literature. Progression of the cataract, an aspect of few studies in this syndrome, appeared to be quite limited in extent. The heterozygous +32G to T ( 168G>T) substitution in the IRE of the FTL gene was detected in this family. CONCLUSIONS: Ophthalmic and biochemical studies together with genetic testing confirmed HCS in three family members. Although the disorder has been extensively described in recent years, little is known regarding cataract evolution over time. In our cases, lens evaluations encompassed many years, identified bilateral cataract of typical morphology and supported the hypothesis that this unique clinical feature of the disease tends to be slowly progressive in nature, at least in adults. PMID- 26849799 TI - Vitamin E neuroprotection against cisplatin ototoxicity: Preliminary results from a randomized, placebo-controlled trial. AB - BACKGROUND: Few studies have investigated the effect of vitamin E in reducing the cisplatin (CDDP)-induced ototoxicity. This study evaluated vitamin E supplementation as a protecting agent against CDDP-induced ototoxicity. METHODS: Patients who started CDDP were randomly assigned to receive vitamin E supplementation at 400 mg per day (group 1) or placebo (group 2). Audiograms and evoked brainstem responses were obtained at baseline, and after 1, 2, and 3 months. RESULTS: Twenty-three patients affected by solid malignancies were enrolled (13 in group 1 and 10 in group 2). At 1 month, a significant hearing loss in group 2 at both 2000 HZ (right ear: p = .05; left ear: p = .04) and 8000 HZ (right ear: p = .04; left ear: p = .03) was detected when compared to baseline values. Audiograms did not show significant changes. At 1 month, evoked brainstem responses remained unchanged in both arms without significant differences between groups. CONCLUSION: These preliminary findings confirm the neuroprotective properties of vitamin E against the CDDP-induced ototoxicity. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2118-E2121, 2016. PMID- 26849800 TI - Fully Atomistic Simulations of the Ionic Liquid Crystal [C16mim][NO3]: Orientational Order Parameters and Voids Distribution. AB - We present a fully atomistic molecular dynamics simulation of the smectic phase of the ionic liquid crystal (ILC) 1-hexadecyl-3-methylimidazolium nitrate, [C16MIm][NO3]. We have characterized the structure of the phase by means of a set of radial distribution functions resolved along the director and in the plane of the smectic layers. The results obtained allow us to discuss the similarities in the microscopic structure of ionic liquids (ILs) and ILCs. In addition to this, we have calculated the orientational order parameters, S, of the methylene groups of the alkyl chain and compared them with the results obtained for phospholipidic membranes from (2)H NMR experiments. We also discuss the orientational order parameters of the imidazolium ring. Finally, we analyze the distribution of voids in the ILC phase. We have found that voids of considerable volume to host a nonpolar gas, e.g. xenon, are localized in the hydrophobic layers and almost absent in the ionic layers. PMID- 26849801 TI - The Increasing Trend in Caesarean Section Rates: Global, Regional and National Estimates: 1990-2014. AB - BACKGROUND: Caesarean section (CS) rates continue to evoke worldwide concern because of their steady increase, lack of consensus on the appropriate CS rate and the associated additional short- and long-term risks and costs. We present the latest CS rates and trends over the last 24 years. METHODS: We collected nationally-representative data on CS rates between 1990 to 2014 and calculated regional and subregional weighted averages. We conducted a longitudinal analysis calculating differences in CS rates as absolute change and as the average annual rate of increase (AARI). RESULTS: According to the latest data from 150 countries, currently 18.6% of all births occur by CS, ranging from 6% to 27.2% in the least and most developed regions, respectively. Latin America and the Caribbean region has the highest CS rates (40.5%), followed by Northern America (32.3%), Oceania (31.1%), Europe (25%), Asia (19.2%) and Africa (7.3%). Based on the data from 121 countries, the trend analysis showed that between 1990 and 2014, the global average CS rate increased 12.4% (from 6.7% to 19.1%) with an average annual rate of increase of 4.4%. The largest absolute increases occurred in Latin America and the Caribbean (19.4%, from 22.8% to 42.2%), followed by Asia (15.1%, from 4.4% to 19.5%), Oceania (14.1%, from 18.5% to 32.6%), Europe (13.8%, from 11.2% to 25%), Northern America (10%, from 22.3% to 32.3%) and Africa (4.5%, from 2.9% to 7.4%). Asia and Northern America were the regions with the highest and lowest average annual rate of increase (6.4% and 1.6%, respectively). CONCLUSION: The use of CS worldwide has increased to unprecedented levels although the gap between higher- and lower-resource settings remains. The information presented is essential to inform policy and global and regional strategies aimed at optimizing the use of CS. PMID- 26849802 TI - A Mismatch between High-Risk Behaviors and Screening of Infectious Diseases among People Who Inject Drugs in Dar es Salaam, Tanzania. AB - BACKGROUND: People who inject drugs are at risk of various infectious diseases. Despite such a risk, evidence is limited which studied the utilization of screening services for common infectious diseases among people who inject drugs in Tanzania. We aimed to examine their high-risk behaviors; utilization of screening services for HIV infection, hepatitis B/C, any other sexually transmitted infection, and tuberculosis; and their associated factors in Dar es Salaam, Tanzania. METHODS: We conducted a baseline cross-sectional study as part of a prospective cohort study of people who inject drugs. We included 578 participants comprising of new enrollees of the integrated methadone-assisted treatment program and those who were selected from the communities but not enrolled in the program. We interviewed new enrollees preceding their enrollment and receipt of services from the program. We measured participants' high-risk behaviors and their utilization of screening services. We analyzed the data descriptively and used multiple logistic regressions to identify the factors associated with ever being screened for infectious diseases. RESULTS: Of 578 participants, 14.2% shared injection needles. Of 547 sexually active participants, 37.5% had multiple sexual partners and only 17.4% used a condom. Of all participants, however, only 36.0% had ever been screened for HIV infection, 18.5% for tuberculosis, 11.8% for any other sexually transmitted infection, and 11.6% for hepatitis B/C. They were more likely to have ever been screened for HIV infection if they had education levels above primary education (adjusted odds ratio [AOR]: 2.54, 95% CI: 1.54-4.20), had a history of transactional sex (OR: 2.63, 95% CI: 1.01-6.84), and were new enrollees of the program (AOR: 7.41, 95% CI: 4.41-12.86). CONCLUSIONS: People who inject drugs practice high-risk behaviors but their utilization of screening services for infectious diseases is poor in Dar es Salaam, Tanzania. It is crucial to increase the coverage of screening services for them and strengthen the counseling of safer sexual practices. PMID- 26849803 TI - Change in Obesity Prevalence across the United States Is Influenced by Recreational and Healthcare Contexts, Food Environments, and Hispanic Populations. AB - OBJECTIVE: To examine change in county-level adult obesity prevalence between 2004 and 2009 and identify associated community characteristics. METHODS: Change in county-level adult (>=20 years) obesity prevalence was calculated for a 5-year period (2004-2009). Community measures of economic, healthcare, recreational, food environment, population structure, and education contexts were also calculated. Regression analysis was used to assess community characteristics associated (p<0.01) with change in adult obesity prevalence. RESULTS: Mean+/-SD change in obesity prevalence was 5.1+/-2.4%. Obesity prevalence decreased in 1.4% (n = 44) and increased in 98% (n = 3,060) of counties from 2004-2009. Results showed that both baseline levels and increases in physically inactive adults were associated with greater increases in obesity prevalence, while baseline levels of and increases in physician density and grocery store/supercenter density were related to smaller increases in obesity rates. Baseline levels of the Hispanic population share were negatively linked to changing obesity levels, while places with greater Hispanic population growth saw greater increases in obesity. CONCLUSIONS: Most counties in the U.S. experienced increases in adult obesity prevalence from 2004 to 2009. Findings suggest that community-based interventions targeting adult obesity need to incorporate a range of community factors, such as levels of physical inactivity, access to physicians, availability of food outlets, and ethnic/racial population composition. PMID- 26849804 TI - Establishment of Leptin-Responsive Cell Lines from Adult Mouse Hypothalamus. AB - Leptin resistance is considered to be the primary cause of obesity. However, the cause of leptin resistance remains incompletely understood, and there is currently no cure for the leptin-resistant state. In order to identify novel drug target molecules that could overcome leptin resistance, it would be useful to develop in vitro assay systems for evaluating leptin resistance. In this study, we established immortalized adult mouse hypothalamus-derived cell lines, termed adult mouse hypothalamus (AMH) cells, by developing transgenic mice in which SV40 Tag was overexpressed in chromogranin A-positive cells in a tamoxifen-dependent manner. In order to obtain leptin-responsive clones, we selected clones based on the phosphorylation levels of STAT3 induced by leptin. The selected clones were fairly responsive to leptin in terms of STAT3, ERK, and Akt phosphorylation and induction of c-Fos mRNA induction. Pretreatment with leptin, insulin, and palmitate attenuated the c-Fos mRNA response to leptin, suggesting that certain aspects of leptin resistance might be reconstituted in this cellular model. These cell lines are useful tools for understanding the molecular nature of the signal disturbance in the leptin-resistant state and for identifying potential target molecules for drugs that relieve leptin resistance, although they have drawbacks including de-differentiated nature and lack of long-time stability. PMID- 26849805 TI - The LPS O-Antigen in Photosynthetic Bradyrhizobium Strains Is Dispensable for the Establishment of a Successful Symbiosis with Aeschynomene Legumes. AB - The photosynthetic bradyrhizobia are able to use a Nod-factor independent process to induce nitrogen-fixing nodules on some semi-aquatic Aeschynomene species. These bacteria display a unique LPS O-antigen composed of a new sugar, the bradyrhizose that is regarded as a key symbiotic factor due to its non immunogenic character. In this study, to check this hypothesis, we isolated mutants affected in the O-antigen synthesis by screening a transposon mutant library of the ORS285 strain for clones altered in colony morphology. Over the 10,000 mutants screened, five were selected and found to be mutated in two genes, rfaL, encoding for a putative O-antigen ligase and gdh encoding for a putative dTDP-glucose 4,6-dehydratase. Biochemical analysis confirmed that the LPS of these mutants completely lack the O-antigen region. However, no effect of the mutations could be detected on the symbiotic properties of the mutants indicating that the O-antigen region of photosynthetic Bradyrhizobium strains is not required for the establishment of symbiosis with Aeschynomene. PMID- 26849806 TI - (99m)Tc-DPD uptake reflects amyloid fibril composition in hereditary transthyretin amyloidosis. AB - Aims In transthyretin amyloid (ATTR) amyloidosis various principal phenotypes have been described: cardiac, neuropathic, or a mixed cardiac and neuropathic. In addition, two different types of amyloid fibrils have been identified (type A and type B). Type B fibrils have thus far only been found in predominantly early onset V30M and in patients carrying the Y114C mutation, whereas type A is noted in all other mutations currently examined as well as in wild-type ATTR amyloidosis. The fibril type is a determinant of the ATTR V30M disease phenotype. (99m)Tc-DPD scintigraphy is a highly sensitive method for diagnosing heart involvement in ATTR amyloidosis. The objective of this study was to determine the relationship between ATTR fibril composition and (99m)Tc-DPD scintigraphy outcome in patients with biopsy-proven ATTR amyloidosis. Methods Altogether 55 patients with biopsy-proven diagnosis of ATTR amyloidosis and amyloid fibril composition determined were examined by (99m)Tc-DPD scintigraphy. The patients were grouped and compared according to their type of amyloid fibrils. Cardiovascular evaluation included ECG, echocardiography, and cardiac biomarkers. The medical records were scrutinized to identify subjects with hypertension or other diseases that have an impact on cardiac dimensions. Results A total of 97% with type A and none of the patients with type B fibrils displayed (99m)Tc-DPD uptake at scintigraphy (p < 0.001). Findings from analyses of cardiac biomarkers, ECG, and echocardiography, though significantly different, could not differentiate between type A and B fibrils in individual patients. Conclusion In ATTR amyloidosis, the outcome of (99m)Tc-DPD scintigraphy is strongly related to the patients' transthyretin amyloid fibril composition. PMID- 26849808 TI - Serial Changes of Quadriceps and Hamstring Muscle Strength Following Total Knee Arthroplasty: A Meta-Analysis. AB - This meta-analysis was performed to analyze serial changes in thigh muscles, including quadriceps and hamstring muscles, from before to one year after total knee arthroplasty (TKA). All studies sequentially comparing isokinetic quadriceps and hamstring muscle strengths between the TKA side and the contralateral uninjured limb were included in this meta-analysis. Five studies with 7 cohorts were included in this meta-analysis. The mean differences in the strengths of quadriceps and hamstring muscles between the TKA and uninjured sides were greatest three months after surgery (26.8 N?m, 12.8 N?m, P<0.001), but were similar to preoperative level at six months (18.4 N?m, 7.4 N?m P<0.001) and were maintained for up to one year (15.9 N?m, 4.1 N?m P<0.001). The pooled mean differences in changes in quadriceps and hamstring strengths relative to preoperative levels were 9.2 N?m and 4.9 N?m, respectively, three months postoperatively (P = 0.041), but were no longer significant after six months and one year. During the year after TKA, quadriceps and hamstring muscle strengths were lowest after 3 months, recovering to preoperative level after six months, but not reaching the muscle strength on the contralateral side. Relative to preoperative levels, the difference in muscle strength between the TKA and contralateral knees was only significant at three months. Because decrease of strength of the quadriceps was significantly greater than decrease in hamstring muscle strength at postoperative three months, early rehabilitation after TKA should focus on recovery of quadriceps muscle strength. PMID- 26849809 TI - Association between moyamoya syndrome and the RNF213 c.14576G>A variant in patients with neurofibromatosis Type 1. AB - OBJECTIVE In a minority of patients with neurofibromatosis Type 1 (NF-1), cerebral vasculopathy reminiscent of moyamoya disease develops. This phenomenon is called moyamoya syndrome (MMS), but there are no known risk factors for the prediction of MMS in NF-1 patients. Polymorphism of the RNF213 gene has exhibited strong associations with familial and sporadic moyamoya disease and other cerebral vasculopathies. The aim of this study is to find whether the RNF213 c.14576G>A variant is associated with MMS development in the NF-1 population or not. METHODS The MMS group included 16 NF-1 patients with documented MMS. The control group consisted of 97 NF-1 patients without MMS. Genomic DNA samples were obtained from the saliva or blood of both groups, and the presence of the RNF213 c.14576G>A variant was assessed by Sanger sequencing. RESULTS In the MMS group, 3 patients had the RNF213 c.14576G>A variant (18.7%), whereas no patients with this genetic variation were observed in the control group (0%). There was a meaningful association between the RNF213 c.14576G>A variant and MMS development (p = 0.0024). The crude odds ratio was calculated as 50.57 (95% CI 1.57-1624.41). All 3 patients with MMS and the c.14576G>A variant were diagnosed with MMS at an early age and had bilateral involvement. CONCLUSIONS The RNF213 c.14576G>A variant is more common in NF-1 patients who develop MMS than in NF-1 patients without MMS. This variant might be a susceptibility gene for the NF-1-moyamoya connection. PMID- 26849810 TI - Outcome of hospital discharge on postoperative Day 1 following uncomplicated tethered spinal cord release. AB - OBJECTIVE Postoperative management following the release of simple spinal cord tethering lesions is highly variable. As a quality improvement initiative, the authors aimed to determine whether an institutional protocol of discharging patients on postoperative day (POD) 1 was associated with a higher rate of postoperative CSF leaks than the prior protocol of discharge on POD 2. METHODS This was a single-center retrospective review of all children who underwent release of a spinal cord-tethering lesion that was not associated with a substantial fascial or dural defect (i.e., simple spinal cord detethering) during 2 epochs: prior to and following the institution of a protocol for discharge on POD 1. Outcomes included the need for and timing of nonroutine care of the surgical site, including return to the operating room, wound suturing, and nonsurgical evaluation and management. RESULTS Of 169 patients identified, none presented with CSF-related complications prior to discharge. In the preintervention group (n = 113), the postoperative CSF leak rate was 4.4% (5/113). The mean length of stay was 2.3 days. In the postintervention group, the postoperative CSF leak rate was 1.9% (1/53) in the patients with postdischarge follow-up. The mean length of stay in that group was 1.3 days. CONCLUSIONS At a single academic children's hospital, a protocol of discharging patients on POD 1 following uncomplicated release of a simple spinal cord-tethering lesion was not associated with an increased rate of postoperative CSF leaks, relative to the previous protocol. The rates identified are consistent with the existing literature. The authors' practice has changed to discharge on POD 1 in most cases. PMID- 26849811 TI - Magnetic resonance-guided laser interstitial thermal therapy: report of a series of pediatric brain tumors. AB - OBJECTIVE Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a novel, minimally invasive treatment that has multiple advantages in pediatric use and broad applicability for different types of lesions. Here, the authors report the preliminary results of the first series of pediatric brain tumors treated with MRgLITT at Golisano Children's Hospital in Syracuse, New York. METHODS Pediatric brain tumors treated with MRgLITT between February 2012 and August 2014 at Golisano Children's Hospital were evaluated retrospectively. Medical records, radiological findings, surgical data, complications, and results of tumor volumetric analyses were reviewed. The Visualase thermal laser system (Medtronic) was used in all MRgLITT procedures. RESULTS This series included 11 patients with 12 tumors (pilocytic astrocytoma, ependymoma, medulloblastoma, choroid plexus xanthogranuloma, subependymal giant cell astrocytoma, and ganglioglioma). A single laser and multiple overlapping ablations were used for all procedures. The mean laser dose was 10.23 W, and the mean total ablation time was 68.95 seconds. The mean initial target volume was 6.79 cm(3), and the mean immediate post-ablation volume was 7.86 cm(3). The mean hospital stay was 3.25 days, and the mean follow-up time was 24.5 months. Tumor volume decreased in the first 3 months after surgery (n = 11; p = 0.007) and continued to decrease by the 4- to 6-month followup (n = 11; mean volume 2.61 cm(3); p = 0.009). Two patients experienced post-ablation complications: transient right leg weakness in one patient, and transient hemiparesis, akinetic mutism, and eye movement disorder in the other. CONCLUSIONS Magnetic resonance-guided laser interstitial thermal therapy is an effective first- or second-line treatment for select pediatric brain tumors. Larger multiinstitutional clinical trials are necessary to evaluate its use for different types of lesions to further standardize practices. PMID- 26849807 TI - The Unfolded Protein Response Plays a Predominant Homeostatic Role in Response to Mitochondrial Stress in Pancreatic Stellate Cells. AB - Activated pancreatic stellate cells (PaSC) are key participants in the stroma of pancreatic cancer, secreting extracellular matrix proteins and inflammatory mediators. Tumors are poorly vascularized, creating metabolic stress conditions in cancer and stromal cells that necessitate adaptive homeostatic cellular programs. Activation of autophagy and the endoplasmic reticulum unfolded protein response (UPR) have been described in hepatic stellate cells, but the role of these processes in PaSC responses to metabolic stress is unknown. We reported that the PI3K/mTOR pathway, which AMPK can regulate through multiple inputs, modulates PaSC activation and fibrogenic potential. Here, using primary and immortalized mouse PaSC, we assess the relative contributions of AMPK/mTOR signaling, autophagy and the UPR to cell fate responses during metabolic stress induced by mitochondrial dysfunction. The mitochondrial uncoupler rottlerin at low doses (0.5-2.5 MUM) was added to cells cultured in 10% FBS complete media. Mitochondria rapidly depolarized, followed by altered mitochondrial dynamics and decreased cellular ATP levels. This mitochondrial dysfunction elicited rapid, sustained AMPK activation, mTOR pathway inhibition, and blockade of autophagic flux. Rottlerin treatment also induced rapid, sustained PERK/CHOP UPR signaling. Subsequently, high doses (>5 MUM) induced loss of cell viability and cell death. Interestingly, AMPK knock-down using siRNA did not prevent rottlerin-induced mTOR inhibition, autophagy, or CHOP upregulation, suggesting that AMPK is dispensable for these responses. Moreover, CHOP genetic deletion, but not AMPK knock-down, prevented rottlerin-induced apoptosis and supported cell survival, suggesting that UPR signaling is a major modulator of cell fate in PaSC during metabolic stress. Further, short-term rottlerin treatment reduced both PaSC fibrogenic potential and IL-6 mRNA expression. In contrast, expression levels of the angiogenic factors HGF and VEGFalpha were unaffected, and the immune modulator IL 4 was markedly upregulated. These data imply that metabolic stress-induced PaSC reprogramming differentially modulates neighboring cells in the tumor microenvironment. PMID- 26849813 TI - Updates in the Pathologic Diagnosis and Classification of Epithelial Neoplasms of Urachal Origin. AB - Since the publication of the World Health Organization "blue book" in 2004, several recent studies have provided new insights on the pathologic aspects of urachal neoplasms. The proposed updates include modified criteria for the diagnosis of urachal carcinoma. A uniform nomenclature for cystic tumors was lacking, and it is recommended that urachal mucinous cystic tumors should be separated and classified in a manner similar to ovarian mucinous neoplasms. The spectrum includes mucinous cystadenoma, mucinous cystic tumor of low malignant potential, mucinous cystic tumor of low malignant potential with intraepithelial carcinoma, and microscopically or frankly invasive mucinous cystadenocarcinoma, with 65% of cystic tumors classified as mucinous cystic tumor of low malignant potential. Most importantly, it has been shown that progression-free survival of noninvasive mucinous cystic tumors is significantly better than noncystic invasive adenocarcinoma. This development, along with prior descriptions of urachal villous adenoma, has also reaffirmed the occurrence of benign tumors of urachal epithelial origin. For noncystic (usual) invasive adenocarcinomas, the traditionally described histologic subtypes of enteric, mucinous, signet ring cell, not otherwise specified, and mixed remain appropriate, with 50% of tumors classified as mucinous subtype. Although this subtyping is helpful in diagnosis and differential diagnosis, the clinical significance of subtyping adenocarcinoma is still uncertain. Rare nonglandular morphologies such as urothelial, squamous, and neuroendocrine carcinoma in urachal carcinomas have been described in detail with proposals for their own set of diagnostic criteria. These criteria are based on unique features of urachal nonglandular carcinomas. Among the immunomarkers studied, only beta-catenin and CK7 may be of help in the distinction of urachal from colorectal adenocarcinoma. Awareness of the expression profile of immunomarkers such as CDX2, P504S (racemase), PSMA, claudin-18, and REG IV in urachal tumors and in tumors in the differential diagnosis is important to avoid overreliance of these markers in the diagnosis. Limited studies have identified KRAS mutations interestingly only in mucinous adenocarcinoma and exclusive of MSI loss, and mutations in BRAF are not present. Several alternative tumor staging approaches (eg, Mayo, Ontario, TNM systems) different from the traditional staging proposed by Sheldon are used that provide better tumor distribution across stages; however, the prognostic utility of the stage substratification has yet to be validated in large prospective studies. Evidence though suggests that staging urachal cancer is most pertinent when dichotomized to tumors that have spread outside versus within the perivesical tissue. Only high tumor stage and residual tumor after surgery have been shown to be independent predictors of outcome. This review updates the contemporary classification of urachal epithelial tumors, which has informed the upcoming 2016 classification of World Health Organization tumors. We provide modified criteria for diagnosing urachal adenocarcinomas, which remains a clinico-pathologic exercise. The role of ancillary diagnostic methodology and issues pertaining to staging and prognostication are presented. PMID- 26849812 TI - A Pilot Study Evaluating the Effectiveness of Platelet-Rich Plasma Therapy for Treating Degenerative Tendinopathies: A Randomized Control Trial with Synchronous Observational Cohort. AB - OBJECTIVE: This pilot study aimed to inform future research evaluating the effectiveness of Platelet Rich Plasma (PRP) injection for tendinopathy. DESIGN: Randomized control trial (RCT) and synchronous observational cohort studies. For the RCT, consecutive consenting patients treated at an academic sports medicine clinic were randomly assigned to either a PRP or placebo control group. SETTING: The Glen Sather Sport Medicine Clinic, Edmonton, Canada. PATIENTS: The RCT included 9 participants with rotator cuff tendinopathy. The cohort study included 178 participants with a variety of tendinopathies. INTERVENTIONS: Patients receiving PRP were injected with 4 ml of platelets into the supraspinatus and/or infraspinatus, while patients in the placebo group were injected with 4 ml of saline. All participants undertook a 3-month standardized, home-based, daily exercise program. MAIN OUTCOME MEASURES: Participants in the RCT were re evaluated 3, and 6 months post-injection. Change scores before and after injection on pain, disability and MRI-documented pathology outcomes were compared. In the cohort study, pain and disability were measured at 1, 2 and 3 months post-injection. RESULTS: For the RCT, 7 participants received PRP and 2 received placebo injections. Patients receiving PRP reported clinically important improvements in pain (>1.5/10 on VAS), disability (>15 point DASH change), and tendon pathology while those receiving placebo injections did not. In the observational cohort, statistically and clinically significant improvements in pain and disability were observed. CONCLUSION: This pilot study provides information for planning future studies of PRP effectiveness. Preliminary results indicate intratendinous, ultrasound-guided PRP injection may lead to improvements in pain, function, and MRI-documented tendon pathology. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN68341698. PMID- 26849814 TI - Laryngeal Squamous Intraepithelial Lesions: An Updated Review on Etiology, Classification, Molecular Changes, and Treatment. AB - Laryngeal carcinogenesis is a multistep process, characterized by an accumulation of genetic changes associated with architectural and cytologic alterations, ranging from squamous hyperplasia to carcinoma in situ and encompassed by the terminology of squamous intraepithelial lesions (SILs). The etiology, classification, genetic changes, and malignant progression of these lesions are reviewed. Tobacco remains the principal etiological factor with gastroesophageal reflux disease recently considered as a possible factor. In contrast, there is little evidence that microbiological agents, especially human papillomavirus infection, are frequently involved in laryngeal carcinogenesis and probably <10% of SILs are driven by biologically active human papillomavirus infection. Light microscopy, despite a degree of subjectivity, remains the mainstay of accurate diagnosis, prognosis, and guidance for a patient's treatment. The currently used classifications, the dysplasia system, squamous intraepithelial neoplasia, and the Ljubljana classification, reflect different standpoints on this important topic. The modified Ljubljana classification, with good interobserver agreement, could be considered as a proposal for a unified classification of laryngeal SILs. This review also briefly discusses recently discovered genetic changes, such as CDKN2A and CTNNB1 genes, and chromosome instability of chromosomes 1 and 7; however, none of these can at present improve histologic diagnosis. Malignant progression of precursor lesions varies from 2% to 74%, according to different studies. Cold-steel microinstruments, CO2 laser, and radiotherapy are used to treat the different grades of precursor lesions. There is as yet no worldwide agreement on the treatment of high-grade lesions and carcinoma in situ. PMID- 26849816 TI - Solitary Fibrous Tumor/Hemangiopericytoma Dichotomy Revisited: A Restless Family of Neoplasms in the CNS. AB - Solitary fibrous tumor (SFT) and hemangiopericytoma (HPC) both entered the literature as separate entities in the early to mid 1900s. In contrast to their central nervous system (CNS) counterparts, there has been a tendency to consider these 2 entities as 1 since the early 1990s, as soft tissue SFT gradually included the tumors previously diagnosed as HPC. The most recent World Health Organization (WHO) classification of the tumors of soft tissue considered the term HPC obsolete, and places all such tumors within the extrapleural SFT category. In contrast, CNS SFT and HPC continue to be regarded as different entities in the latest version of the WHO CNS tumor classification. A change in this approach is currently being considered for the upcoming revision of the WHO scheme, but it is not quite clear whether such a change will be as drastic as the one adopted by the soft tissue and bone tumor working group. This article focuses on the historical evolution of these 2 labels as primary CNS neoplasms, and reviews their differences and similarities in terms of clinical, pathologic, and molecular features. PMID- 26849817 TI - Patient Safety Curriculum for Anatomic Pathology Trainees: Recommendations Based on Institutional Experience. AB - Because of the unique systems and skills involved in patient care by the pathologist, it is challenging to design and implement relevant training in patient safety for pathology trainees. We propose a patient safety curriculum for anatomic pathology (AP) residents based on our institutional experience. The Hospital of the University of the Pennsylvania employs a self-reporting safety database. The occurrences from July 2013 to June 2015 recorded in this system that involved the division of AP were reviewed and cataloged as preanalytic, analytic, and postanalytic. The distribution of these occurrences was then used to create a framework for curriculum development in AP. We identified areas in which trainees are involved in the identification and prevention of common patient safety errors that occur in our AP department. Using these data-proven target areas, and employing current Accreditation Council for Graduate Medical Education recommendations and patient safety literature, a strategy for delivering relevant patient safety training is proposed. Teaching patient safety to pathology trainees is a challenging, yet necessary, component of AP training programs. By analyzing the patient safety errors that occur in the AP department, relevant and actionable training can be developed. This provides quality professional development and improves overall performance as trainees are integrated into laboratory systems. PMID- 26849818 TI - Mobile Technology for the Practice of Pathology. AB - Recently, several technological advances have been introduced to mobile phones leading some people to refer to them as "smartphones." These changes have led to widespread consumer adoption. A similar adoption has occurred within the medical field and this revolution is changing the practice of medicine, including pathology. Several mobile applications have been published for dermatology, orthopedics, ophthalmology, neurosurgery, and clinical pathology. The applications are wide ranging, including mobile technology to increase patient engagement, self-monitoring by patients, clinical algorithm calculation, facilitation between experts to resource-poor environments. These advances have been received with mixed reviews. For anatomic pathology, mobile technology applications can be broken into 4 broad categories: (a) educational uses, (b) microscope with mobile phone, (c) mobile phone as microscope/acquisition device, and (d) miscellaneous. Using a mobile phone as an acquisition device paired with a microscope seems to be the most interesting current application because of the need for expert consultation with resource-poor environments. However, several emerging uses for mobile technology may become more prominent as the technology matures including image analysis, alternative light sources, and increased opportunities for clinician and patient engagement. The flexibility represented by mobile technology represents a burgeoning field in pathology informatics. PMID- 26849815 TI - The State of the Art in Colorectal Cancer Molecular Biomarker Testing. AB - The number of molecular biomarkers to inform treatment decisions in patients with metastatic colorectal cancer (mCRC) continues to expand and with it the methodologies that can be employed to evaluate these biomarkers. Beyond standard diagnostic and prognostic biomarkers, such as those used for Lynch syndrome, mutations in KRAS exon 2 are well established as predictive for lack of response to the antiepidermal growth factor receptor therapies panitumumab and cetuximab. Recent studies have extended these findings by demonstrating that mutations in KRAS exons 3 and 4 and in NRAS exons 2, 3, and 4 (with all KRAS and NRAS mutations collectively referred to as RAS) are also predictive for treatment outcomes among patients with mCRC receiving panitumumab and cetuximab in combination with chemotherapy or as monotherapy. Consequently, evaluation of these additional loci has been incorporated into current clinical guidelines, and pathologists will need to develop testing procedures and algorithms to reliably and rapidly evaluate RAS status. With the increased number of mutations that must be examined to evaluate the status of RAS and other emerging biomarkers, next generation sequencing technologies are likely to become increasingly important in mCRC testing. This review describes new considerations for pathologists that have arisen as a consequence of the incorporation of additional biomarker testing into clinical practice for mCRC. PMID- 26849819 TI - Laboratory Information Systems in Molecular Diagnostics: Why Molecular Diagnostics Data are Different. AB - Molecular diagnostic testing presents new challenges to information management that are yet to be sufficiently addressed by currently available information systems for the molecular laboratory. These challenges relate to unique aspects of molecular genetic testing: molecular test ordering, informed consent issues, diverse specimen types that encompass the full breadth of specimens handled by traditional anatomic and clinical pathology information systems, data structures and data elements specific to molecular testing, varied testing workflows and protocols, diverse instrument outputs, unique needs and requirements of molecular test reporting, and nuances related to the dissemination of molecular pathology test reports. By satisfactorily addressing these needs in molecular test data management, a laboratory information system designed for the unique needs of molecular diagnostics presents a compelling reason to migrate away from the current paper and spreadsheet information management that many molecular laboratories currently use. This paper reviews the issues and challenges of information management in the molecular diagnostics laboratory. PMID- 26849820 TI - Doxycycline in Eradication Therapy of Helicobacter pylori--a Systematic Review and Meta-Analysis. AB - BACKGROUND: Since resistance of Helicobacter pylori is developing very fast all over the world, new treatment regimens for eradication are urgently needed. AIM: To compare eradication success rate of H. pylori treatment regimens with and without doxycycline. METHODS: English medical literature searches were conducted for regimens including doxycycline for eradication of H. pylori. Searches were performed up to August 31, 2015, using MEDLINE, PubMed, EMBASE, Scopus and CENTRAL. Meta-analysis was performed by using comprehensive meta-analysis software. Pooled ORs and 95% CIs were calculated comparing treatment regimens for eradication of H. pylori infection with and without doxycycline. RESULTS: The OR for eradication success rate in a fixed model was in favor for treatment regimens with doxycycline: 1.292, 95% CI 1.048-1.594, p = 0.016. There was no significant heterogeneity in the included studies: Q = 15.130, d.f. (Q) = 8, I2 = 47.126, p > 0.10. When treatment regimens with doxycycline were compared only with treatment regimens with tetracycline, no significant difference was found in eradication success rate: OR 0.95, 95% CI 0.68-1.32, p = 0.77. But when treatment regimens with doxycycline were compared with treatment regimens without tetracycline, the OR in favor of doxycycline was even higher: OR 1.59, 95% CI 1.21-2.09, p < 0.001. CONCLUSION: In this meta-analysis, we confirmed doxycycline efficiency in the eradication of H. pylori. Thus, triple, quadruple or even high dose dual therapy with regimens containing doxycycline should be considered. PMID- 26849821 TI - Nifedipine Treatment for Hypertension is Associated with Enhanced Lipolytic Activity and Accelerated Clearance of Postprandial Lipemia. AB - Hypertension, advanced age, postprandial hyperlipidemia, and insulin resistance are major risk factors for atherosclerosis. The calcium channel blocker nifedipine is reported to ameliorate insulin resistance possibly by activating PPARgamma. This is expected to become accentuated in elderly individuals due to age-related insulin resistance. Insulin resistance modulates lipoprotein metabolism. Therefore, we reasoned that nifedipne offers the potential for improving postprandial lipemia in association with increasing age. We studied the effect of nifedipine on fasting lipids, postprandial lipemia, insulin sensitivity, and plasma lipolytic activity in 24 and 15 hypertensive subjects aged 70-75 years and 40-45 years, respectively. As expected, nifedipine significantly lowered systolic and diastolic blood pressure. Nifedipine decreased fasting triglyceride level (23%) and increased HDL-C (15%) in the elderly group. At baseline, postprandial triglyceride levels were remarkably elevated in elderly compared to younger patients (1 288+/-798 vs. 501+/-260 mg.dl(-1).h, p<0.05), as was retinyl palmitate (surrogate marker for intestinally-derived cholesterol) in the chylomicrons (45.0+/-26.5 vs. 23.4+/-10.6 mg.l(-1).h, p<0.05) and chylomicron remnant (15.2+/-5.4 vs. 11.7+/-4.7 mg.l(-1).h, p<0.05) fractions. Importantly, while the level of chylomicron remnants in the group of younger subjects remained unchanged after treatment, nifedipine was associated with a significantly decreased chylomicron remnants retinyl palmitate in the elderly group, which dropped to levels, observed in younger subjects. This was accompanied by enhanced insulin sensitivity and augmented plasma lipolytic activity. The present work suggests that nifedipine has favorable metabolic effects that are beyond the known enhancement of insulin sensitivity. The improvement in postprandial lipidemia by nifedipine may add to its anti-atherogenic effects in hypertensive patients. PMID- 26849822 TI - Evolution of Glucose Tolerance After Treatment of Acromegaly: A Study in 57 Patients. AB - The aim of our study was to evaluate the evolution of glucose metabolism in 57 patients after treatment of their acromegaly and to determine risk factors for the persistence of abnormal glucose tolerance. Therefore, we performed IGF-I measurements, oral glucose tolerance tests (OGTTs), and HOMA to evaluate insulin sensitivity (HOMA-S) and beta-cell function (HOMA-beta) at diagnosis and at last visit (median follow-up 7 years). At diagnosis of acromegaly, 14 patients (25%) were diabetic and 15 (26%) had impaired glucose tolerance, whereas at the last visit, 32% were diabetic and 26% remained glucose intolerant. There was a decrease in fasting glucose (median - 7.0 mg/dl) in the 20 patients cured by surgery, whereas it increased in the 28 patients controlled under medical therapy (median + 2.0 mg/dl; p<0.05 vs. cured group) and in the 9 patients with active disease (median + 4.0 mg/dl). Loss of beta-cell function was more pronounced in the patients under medical treatment (median - 87.9%) vs. the cured group (median - 30.4%; p<0.05). There was a decrease in HbA1c between diagnosis and last visit in patients under pegvisomant (mean - 19.2 mmol/mol) vs. a small increase in patient treated by somatostatin analogues (+ 3.4 mmol/mol; p<0.05). Independent risk factors for persistent abnormal glucose tolerance were the glucose tolerance status at diagnosis and ongoing treatment with somatostatin analogues. In conclusion, we found that more than 50% of patients still have IGT or diabetes after treatment of acromegaly. Improvement of glucose metabolism is mainly observed in cured patients and in patients treated with pegvisomant. PMID- 26849823 TI - Screening for Acromegaly in Patients with Carpal Tunnel Syndrome: A Prospective Study (ACROCARP). AB - Early diagnosis of acromegaly prevents irreversible comorbidities and facilitates surgical cure. Carpal tunnel syndrome (CTS) is common in acromegaly and patients have often undergone surgery for CTS prior to the diagnosis of acromegaly. We hypothesized that screening CTS-patients for acromegaly could facilitate active case-finding. We prospectively enrolled 196 patients [135 women, 56.9 (range 23 103) years] who presented with CTS for surgery. Patients were asked about 6 symptoms suggestive of acromegaly using a questionnaire calculating a symptom score (0-6 points), and insulin-like-growth factor 1 (IGF-1) was measured. If IGF 1 was increased, IGF-1 measurement was repeated, and random growth hormone (GH) and/or an oral glucose tolerance test (OGTT) with assessment of GH-suppression were performed. The mean symptom score was 1.7+/-1.3 points. Three patients reported the maximal symptom score of 6 points, but none of them had an increased IGF-1. There was no correlation between the symptom score and IGF-1-SDS (standard deviation score) (r=0.026; p=0.71). Four patients had an IGF-1>2 SDS. In 2 patients acromegaly was ruled out using random GH and OGTT. One patient had normal IGF-1 and random GH at follow-up. One patient refused further diagnostics. In this prospective cohort of patients with CTS, the observed frequency of acromegaly was at most 0.51% (95% CI 0.03 to 2.83%). In this prospective study, none of the 196 patients with CTS had proven acromegaly. Thus, we see no evidence to justify general screening of patients with CTS for acromegaly. PMID- 26849824 TI - In Vitro Effects of Pioglitazone on the Expression of Components of Wnt Signaling Pathway and Markers of Bone Mineralization. AB - Pioglitazone is an insulin-sensitizing thiazolidinedione (TZD) whose use is associated with bone loss. We examined the effects of pioglitazone on components of the Wnt signaling pathway (Wnt1, beta-catenin) and markers of bone mineralization [osteoprotegerin (OPG), bone sialoprotein (BSP), fibroblast growth factor (FGF)23] as well as mineral content in human osteoblast hFOB 1.19 cells. hFOB 1.19 cells were cultured in K12/DMD medium with or without pioglitazone. PPARgamma Wnt1, OPG, BSP, or FGF23 mRNA expression was measured using qRT-PCR; beta-catenin, OPG, BSP, or FGF23 using ELISA; and calcium or phosphate content using colorimetry. Treatment with pioglitazone resulted in increased expression of PPARgamma mRNA in hFOB 1.19 osteoblasts. Pioglitazone decreased Wnt1 mRNA levels and suppressed components of Wnt signaling pathway as evidenced by a decrease in beta-catenin gene expression and secretion as well as beta-catenin specific activity. The expression and the activity of OPG, BSP, and FGF23 were also reduced by pioglitazone together with total (but not specific) calcium and phosphate content. Pioglitazone affects Wnt1 signaling pathway and mineral matrix regulation components in human osteoblasts. PMID- 26849825 TI - Effect of Telmisartan or Insulin on the Expression of Adiponectin and its Receptors in the Testis of Streptozotocin-Induced Diabetic Rats. AB - This study investigated the effect of insulin and telmisartan on the expression of adiponectin and its receptors, oxidative stress, and inflammatory cytokines in the testis of streptozotocin-induced diabetic rats. Male Wistar rats were randomly divided into control (C, n=8), diabetic (D, n=8), diabetic treated with insulin (DI, n=8), and diabetic treated with telmisartan (DT, n=8). Diabetic was induced by the peritoneal injection of a single dose of streptozotocin. Eight weeks later, bilateral testes were immediately removed after the rat was sacrificed. Epididymis was harvested to prepare sperm suspension. Plasma adiponectin, testicular interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-alpha) were detected by enzyme linked immunosorbent assay (ELISA). The mRNA or protein expression of testicular adiponectin receptor 1 (adipoR1) and 2 (adipoR2), p22phox, transcription factor NF-E2 associated factor 2 (Nrf2), NAD(P)H quinone oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), AMPK-alpha, Akt, and eNOS was assayed by real-time fluorescence quantitative PCR or Western blot. There were significant pathological changes in the testes of diabetic rats. The levels of testicular weight, sperm number and motility, serum and testicular testosterone, plasma insulin and adiponectin, testicular adiponectin and its receptor 1, Nrf2, NQO1, HO-1, and phosphorylated-AMPK were significantly decreased in diabetic rats. The levels of blood glucose and lipids, and the levels of testicular p22phox, IL-6, TNF-alpha, phosphorylated-AKT, e-NOS, and nitric oxide (NO) were significantly increased in diabetic rats. These changes could be significantly reversed by insulin treatment. Similar results were observed with telmisartan treatment except for NQO1 mRNA and phosphorylated-AMPK. There was no significant difference in the expression of testicular adiponectin receptor 2 among 4 groups. The decreased adiponectin and its receptors, and the increased oxidative stress and inflammatory cytokines may play an important role in the testopathy of type 1 diabetic rats. Insulin and telmisartan may produce the protective effect on the testes of diabetic rats by upregulating the expression of adiponectin and its receptors and downregulating the level of oxidative stress and inflammatory cytokines. PMID- 26849826 TI - Exploring the Leaf Beetle Fauna (Coleoptera: Chrysomelidae) of an Ecuadorian Mountain Forest Using DNA Barcoding. AB - BACKGROUND: Tropical mountain forests are hotspots of biodiversity hosting a huge but little known diversity of insects that is endangered by habitat destruction and climate change. Therefore, rapid assessment approaches of insect diversity are urgently needed to complement slower traditional taxonomic approaches. We empirically compare different DNA-based species delimitation approaches for a rapid biodiversity assessment of hyperdiverse leaf beetle assemblages along an elevational gradient in southern Ecuador and explore their effect on species richness estimates. METHODOLOGY/PRINCIPAL FINDINGS: Based on a COI barcode data set of 674 leaf beetle specimens (Coleoptera: Chrysomelidae) of 266 morphospecies from three sample sites in the Podocarpus National Park, we employed statistical parsimony analysis, distance-based clustering, GMYC- and PTP-modelling to delimit species-like units and compared them to morphology-based (parataxonomic) species identifications. The four different approaches for DNA-based species delimitation revealed highly similar numbers of molecular operational taxonomic units (MOTUs) (n = 284-289). Estimated total species richness was considerably higher than the sampled amount, 414 for morphospecies (Chao2) and 469-481 for the different MOTU types. Assemblages at different elevational levels (1000 vs. 2000 m) had similar species numbers but a very distinct species composition for all delimitation methods. Most species were found only at one elevation while this turnover pattern was even more pronounced for DNA-based delimitation. CONCLUSIONS/SIGNIFICANCE: Given the high congruence of DNA-based delimitation results, probably due to the sampling structure, our study suggests that when applied to species communities on a regionally limited level with high amount of rare species (i.e. ~50% singletons), the choice of species delimitation method can be of minor relevance for assessing species numbers and turnover in tropical insect communities. Therefore, DNA-based species delimitation is confirmed as a valuable tool for evaluating biodiversity of hyperdiverse insect communities, especially when exact taxonomic identifications are missing. PMID- 26849827 TI - An Unusual Case of Oral Metastasis from Rectal Adenocarcinoma Precipitated by Iatrogenicity. PMID- 26849828 TI - Identification of beta-glucosidase 1 as a biomarker and its high expression in hepatocellular carcinoma is associated with resistance to chemotherapy drugs. AB - CONTEXT AND OBJECTIVE: Long-term prognosis of hepatocellular carcinoma (HCC) patients is challenging, and novel biomarkers are needed to predict patient risk and serve as potential therapeutic target. RESULTS: We found beta-glucosidase 1 is significantly overexpressed and activated in primary HCC tissue and multiple HCC cell lines. beta-Glucosidase 1 expression is associated with predicting prognosis of HCC patients under chemotherapy. Silencing beta-glucosidase 1 inhibits growth and survival of HCC cells, with preferential inhibitory effects on high beta-glucosidase 1-expressing cells. Combination of chemo drug with beta glucosidase 1 inhibitor sensitized HCC cells to chemotherapy. CONCLUSION: Our data support beta-glucosidase 1 as a HCC biomarker due to its prognosis significance. PMID- 26849829 TI - APOL1 Polymorphisms in a Deceased Donor and Early Presentation of Collapsing Glomerulopathy and Focal Segmental Glomerulosclerosis in Two Recipients. AB - Two common polymorphisms in APOL1 (G1 and G2) are conserved in persons of African ancestry, and the presence of two polymorphisms (commonly referred to as risk variants) has been identified as a risk factor for chronic kidney disease and focal seg-mental glomerulosclerosis. In kidney transplantation, deceased donors with two APOL1 risk variants carry an increased risk of renal allograft failure in the recipient. An emerging question is whether these data should influence deceased donor assessment or be used to refine prediction of allograft survival. We present the first detailed report of two cases of recipient glomerular disease in the first year following transplant from a deceased donor later defined as carrying two APOL1 risk variants. A possible "second hit" predisposing to renal disease in these recipients is discussed, one with active cytomegalovirus infection concurrent with collapsing glomerulopathy and renal failure and the other with chronic, slowly healing wound infection and focal segmental glomeru losclerosis but stable renal function. In retrospect, awareness of the donor APOL1 risk alleles would not have influenced donor selection and ultimately did not influence posttransplant management. These case reports inform further discussion of the value of APOL1 testing for deceased donors. PMID- 26849830 TI - Automatic Control of Veno-Venous Extracorporeal Lung Assist. AB - Veno-venous extracorporeal lung assist (ECLA) can provide sufficient gas exchange even in most severe cases of acute respiratory distress syndrome. Commercially available systems are manually controlled, although an automatically controlled ECLA could allow individualized and continuous adaption to clinical requirements. Therefore, we developed a demonstrator with an integrated control algorithm to keep continuously measured peripheral oxygen saturation and partial pressure of carbon dioxide constant by automatically adjusting extracorporeal blood and gas flow. The "SmartECLA" system was tested in six animal experiments with increasing pulmonary hypoventilation and hypoxic inspiratory gas mixture to simulate progressive acute respiratory failure. During a cumulative evaluation time of 32 h for all experiments, automatic ECLA control resulted in a peripheral oxygen saturation >=90% for 98% of the time with the lowest value of 82% for 15 s. Partial pressure of venous carbon dioxide was between 40 and 49 mm Hg for 97% of the time with no value <35 mm Hg or >49 mm Hg. With decreasing inspiratory oxygen concentration, extracorporeal oxygen uptake increased from 68 +/- 25 to 154 +/- 34 mL/min (P < 0.05), and reducing respiratory rate resulted in increasing extracorporeal carbon dioxide elimination from 71 +/- 37 to 92 +/- 37 mL/min (P < 0.05). The "SmartECLA" demonstrator allowed reliable automatic control of the extracorporeal circuit. Proof of concept could be demonstrated for this novel automatically controlled veno-venous ECLA circuit. PMID- 26849832 TI - Body Talk: Body Image Commentary on Queerty.com. AB - In this study, we conducted a content analysis of 243 photographic images of men published on the gay male-oriented blog Queerty.com. We also analyzed 435 user generated comments from a randomly selected 1-year sample. Focusing on images' body types, we found that the range of body types featured on the blog was quite narrow-the vast majority of images had very low levels of body fat and very high levels of muscularity. Users' body image-related comments typically endorsed and celebrated images; critiques of images were comparatively rare. Perspectives from objectification theory and social comparison theory suggest that the images and commentary found on the blog likely reinforce unhealthy body image in gay male communities. PMID- 26849831 TI - Impact of catheter size on reliability of quantitative coronary angiographic measurements (comparison of 4Fr and 6Fr catheters). AB - To evaluate the feasibility of catheter down sizing for QCA, the reliability of a 4Fr catheter as a calibration device was evaluated. Repeated coronary angiograms of 9 lesions were obtained using 4Fr and 6Fr catheters under otherwise identical conditions. The calibration factor was measured 10 times by 4Fr and 6Fr catheters. QCA measurements including minimal lumen diameter (MLD), interpolated normal reference (Int N), percent diameter stenosis (%DS), and lesion length (LL) were performed by two technicians twice with a 3-month interval. The intraobserver and interobserver variability of each parameter was evaluated using intraclass correlation coefficients (ICCs). Mean of mean SD of calibration factor was significantly larger in 4Fr than in 6Fr in 9 lesions. The mean of mean coefficient of variance was significantly larger in 4Fr catheters vs in 6Fr catheters. A 6Fr catheter showed excellent reliability for both intraobserver and interobserver variability in MLD, Int N, %DS, and LL. In contrast, 4Fr showed that reliability in intraobserver variability depended on the analyst. Although reliability of interobserver variability in Int N measured by the 4Fr catheter was >0.80, the value was less than that by the 6Fr catheter. Taking these results into consideration, 4Fr catheters are less reliable than 6Fr catheters when measuring QCA data especially for follow-up data that need most accurate measurements of MLD and %DS. It would be better to use a 6Fr catheter to evaluate QCA measurements such as acute gain, late loss, restenosis rate, and device size. PMID- 26849834 TI - Tutorial: Parallel Computing of Simulation Models for Risk Analysis. AB - Simulation models are widely used in risk analysis to study the effects of uncertainties on outcomes of interest in complex problems. Often, these models are computationally complex and time consuming to run. This latter point may be at odds with time-sensitive evaluations or may limit the number of parameters that are considered. In this article, we give an introductory tutorial focused on parallelizing simulation code to better leverage modern computing hardware, enabling risk analysts to better utilize simulation-based methods for quantifying uncertainty in practice. This article is aimed primarily at risk analysts who use simulation methods but do not yet utilize parallelization to decrease the computational burden of these models. The discussion is focused on conceptual aspects of embarrassingly parallel computer code and software considerations. Two complementary examples are shown using the languages MATLAB and R. A brief discussion of hardware considerations is located in the Appendix. PMID- 26849833 TI - Inhibitors of Growth 1b Suppresses Peroxisome Proliferator-Activated Receptor beta/delta Expression Through Downregulation of Hypoxia-Inducible Factor 1alpha in Osteoblast Differentiation. AB - Bone formation, a highly regulated developmental process, involves osteoblast differentiation, which is controlled by different important transcription factors. Recent evidence has suggested possible negative regulation of inhibitors of growth (ING) 1b on the osteoblast marker expression. The aim of this study is to examine the detailed mechanism by which the activity of ING1b inhibits osteoblast differentiation. In the current study, we investigated the function and mechanism by which ING1b inhibits osteoblast differentiation using C3H10T1/2 mesenchymal stem cells and MC3T3-E1 preosteoblasts. Real-time polymerase chain reaction and Western blotting showed that ING1b was decreased during osteoblast differentiation and ING1b overexpression markedly decreased alkaline phosphatase (ALP) activity, runt-related transcription factor 2 (Runx2) expression, and collagen type 1 synthesis, whereas ING1b silencing significantly upregulated ALP activity, Runx2 expression, and collagen type 1 synthesis. Further studies indicated that ING1b suppressed the expression of peroxisome proliferator activated receptor (PPAR)-beta/delta in a hypoxia-inducible factor (HIF) 1alpha dependent manner, while ING1b silencing significantly increased the expression of PPAR-beta/delta and HIF1alpha. Moreover, PPAR-beta/delta or HIF1alpha silencing significantly inhibited ALP activity, Runx2 expression, and collagen type 1 synthesis. These results demonstrated that ING1b is an important regulator of osteoblast differentiation and suppresses PPAR-beta/delta. Our study may provide additional insight into osteoblast differentiation and offer a potential new molecular target for osteoporosis. PMID- 26849835 TI - Diversity and functional traits of culturable microbiome members, including cyanobacteria in the rice phyllosphere. AB - The diversity and abundance of culturable microbiome members of the rice phyllosphere was investigated using cv. Pusa Punjab Basmati 1509. Both diversity and species richness of bacteria were significantly higher in plants in pots in a semi-controlled environment than those in fields. Application of fertilisers reduced both diversity and species richness in field-grown plants under a conventional flooded system of rice intensification (SRI) and in dry-seeded rice (DSR) modes. Sequence analyses of 16S rDNA of culturable bacteria, those selected after amplified ribosomal DNA restriction analysis (ARDRA), showed the dominance of alpha-proteobacteria (35%) and actinobacteria (38%); Pantoea, Exiguobacterium and Bacillus were common among the culturable phyllospheric bacteria. About 34% of 83 culturable bacterial isolates had higher potential (>2 MUg.ml(-1) ) for indole acetic acid production in the absence of tryptophan. Interestingly, the phyllosphere bacterial isolates from the pot experiment had significantly higher potential for nitrogen fixation than isolates from the field experiment. Enrichment for cyanobacteria showed both unicellular forms and non-heterocystous filaments under aerobic as well as anaerobic conditions. PCR-DGGE analysis of these showed that aerobic and anaerobic conditions as well as the three modes of cultivation of rice in the field strongly influenced the number and abundance of phylotypes. The adaptability and functional traits of these culturable microbiome members suggest enormous diversity in the phyllosphere, including potential for plant growth promotion, which was also significantly influenced by the different methods of growing rice. PMID- 26849836 TI - Using travel times to simulate multi-dimensional bioreactive transport in time periodic flows. AB - In travel-time models, the spatially explicit description of reactive transport is replaced by associating reactive-species concentrations with the travel time or groundwater age at all locations. These models have been shown adequate for reactive transport in river-bank filtration under steady-state flow conditions. Dynamic hydrological conditions, however, can lead to fluctuations of infiltration velocities, putting the validity of travel-time models into question. In transient flow, the local travel-time distributions change with time. We show that a modified version of travel-time based reactive transport models is valid if only the magnitude of the velocity fluctuates, whereas its spatial orientation remains constant. We simulate nonlinear, one-dimensional, bioreactive transport involving oxygen, nitrate, dissolved organic carbon, aerobic and denitrifying bacteria, considering periodic fluctuations of velocity. These fluctuations make the bioreactive system pulsate: The aerobic zone decreases at times of low velocity and increases at those of high velocity. For the case of diurnal fluctuations, the biomass concentrations cannot follow the hydrological fluctuations and a transition zone containing both aerobic and obligatory denitrifying bacteria is established, whereas a clear separation of the two types of bacteria prevails in the case of seasonal velocity fluctuations. We map the 1-D results to a heterogeneous, two-dimensional domain by means of the mean groundwater age for steady-state flow in both domains. The mapped results are compared to simulation results of spatially explicit, two-dimensional, advective-dispersive-bioreactive transport subject to the same relative fluctuations of velocity as in the one-dimensional model. The agreement between the mapped 1-D and the explicit 2-D results is excellent. We conclude that travel time models of nonlinear bioreactive transport are adequate in systems of time periodic flow if the flow direction does not change. PMID- 26849837 TI - Different low-molecular-mass organic acids specifically control leaching of arsenic and lead from contaminated soil. AB - Low-molecular-mass organic acids (LMMOA) are of key importance for mobilisation and fate of metals in soil, by functioning as ligands that increase the amount of dissolved metal in solution or by dissociation of metal binding minerals. Column leaching experiments were performed on soil polluted with As and Pb, in order to determine the specificity of LMMOA related release for individual elements, at varying organic acid concentrations. Acetic, citric and oxalic acids were applied in 12h leaching experiments over a concentration range (0.5-25 mM) to soil samples that represent organic and mineral horizons. The leaching of As followed the order: oxalic>citric>acetic acid in both soils. Arsenic leaching was attributed primarily to ligand-enhanced dissolution of mineral oxides followed by As released into solution, as shown by significant correlation between oxalic and citric acids and content of Al and Fe in leaching solutions. Results suggest that subsurface mineral soil layers are more vulnerable to As toxicity. Leaching of Pb from both soils followed the order: citric>oxalic>acetic acid. Mineral soil samples were shown to be more susceptible to leaching of Pb than samples characterised by a high content of organic matter. The leaching efficiency of citric acid was attributed to formation of stable complexes with Pb ions, which other acids are not capable of. Results obtained in the study are evidence that the extent of As and Pb leaching in contaminated surface and subsurface soil depends significantly on the types of carboxylic acid involved. The implications of the type of acid and the specific element that can be mobilised become increasingly significant where LMMOA concentrations are highest, such as in rhizosphere soil. PMID- 26849839 TI - Comparison of LC-UV and LC-MS methods for simultaneous determination of teriflunomide, dimethyl fumarate and fampridine in human plasma: application to rat pharmacokinetic study. AB - This study describes a comparison between LC-UV and LC-MS method for the simultaneous analyses of a few disease-modifying agents of multiple sclerosis. Quantitative determination of fampridine (FAM), teriflunomide (TFM) and dimethyl fumarate (DMF) was performed in human plasma with the recovery values in the range of 85-115%. A reversed-phase high-performance liquid chromatography (HPLC) with UV as well as MS detection is used. The method utilizes an XBridge C18 silica column and a gradient elution with mobile phase consisting of ammonium formate and acetonitrile at a flow rate of 0.5 mL min(-1) . The method adequately resolves FAM, TFM and DMF within a run time of 15 min. Owing to low molecular weights, the estimation of DMF and FAM is more versatile in UV than MS detection. With LC-UV, the detection limits of FAM, TFM and DMF were 0.1, 0.05, 0.05 MUg and the quantification limit for all the analytes was 1 MUg. With LC-MS, the detection and quantification limits for all of the analytes were 1 and 5 ng, respectively. The two techniques were completely validated and shown to be reproducible and sensitive. They were applied to a pharmacokinetic study in rats by a single oral dose. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26849838 TI - The neural circuits of mating and fighting in male mice. AB - Tinbergen proposed that instinctive behaviors can be divided into appetitive and consummatory phases. During mating and aggression, the appetitive phase contains various actions to bring an animal to a social target and the consummatory phase allows stereotyped actions to take place. Here, we summarize recent advances in elucidating the neural circuits underlying the appetitive and consummatory phases of sexual and aggressive behaviors with a focus on male mice. We outline the role of the main olfactory inputs in the initiation of social approach; the engagement of the accessory olfactory system during social investigation, and the role of the hypothalamus and its downstream pathways in orchestrating social behaviors through a suite of motor actions. PMID- 26849840 TI - Local delivery methods of therapeutic agents in the treatment of diffuse intrinsic brainstem gliomas. AB - Brainstem gliomas comprise 10-20% of all pediatric central nervous system (CNS) tumors and diffuse intrinsic pontine gliomas (DIPGs) account for the majority of these lesions. DIPG is a rapidly progressive disease with almost universally fatal outcomes and a median survival less than 12 months. Current standard-of care treatment for DIPG includes radiation therapy, but its long-term survival effects are still under debate. Clinical trials investigating the efficacy of systemic administration of various therapeutic agents have been associated with disappointing outcomes. Recent efforts have focused on improvements in chemotherapeutic agents employed and in methods of localized and targeted drug delivery. This review provides an update on current preclinical and clinical studies investigating treatment options for brainstem gliomas. PMID- 26849841 TI - Optical mammography: bilateral breast symmetry in hemoglobin saturation maps. AB - We present a study of the bilateral symmetry of human breast hemoglobin saturation maps measured with a broadband optical mammography instrument. We have imaged 21 patients with unilateral breast cancer, 32 patients with unilateral benign lesions, and 27 healthy patients. An image registration process was applied to the bilateral hemoglobin saturation (SO 2 SO2 ) images by assigning each pixel to the low, middle, or high range of SO 2 SO2 values, where the thresholds for the categories were the 15th and 85th percentiles of the individual saturation range. The Dice coefficient, which is a measure of similarity, was calculated for each patient's pair of right and left breast SO 2 SO2 images. The invasive cancer patients were found to have an average Dice coefficient value of 0.55+/-0.07 0.55+/-0.07 , which was significantly lower than the benign and healthy groups (0.61+/-0.11 0.61+/-0.11 and 0.62+/-0.12 0.62+/ 0.12 , respectively). Although differences were seen in a group analysis, the healthy patient Dice coefficients spanned a wide range, limiting the diagnostic capabilities of this SO 2 SO2 symmetry analysis on an individual basis. Our results suggest that for assessing the SO 2 SO2 contrast of breast lesions, it may be better to select a reference tissue in the ipsilateral rather than the contralateral breast. PMID- 26849842 TI - A New Equation to Estimate Muscle Mass from Creatinine and Cystatin C. AB - BACKGROUND: With evaluation for physical performance, measuring muscle mass is an important step in detecting sarcopenia. However, there are no methods to estimate muscle mass from blood sampling. METHODS: To develop a new equation to estimate total-body muscle mass with serum creatinine and cystatin C level, we designed a cross-sectional study with separate derivation and validation cohorts. Total body muscle mass and fat mass were measured using dual-energy x-ray absorptiometry (DXA) in 214 adults aged 25 to 84 years who underwent physical checkups from 2010 to 2013 in a single tertiary hospital. Serum creatinine and cystatin C levels were also examined. RESULTS: Serum creatinine was correlated with muscle mass (P < .001), and serum cystatin C was correlated with body fat mass (P < .001) after adjusting glomerular filtration rate (GFR). After eliminating GFR, an equation to estimate total-body muscle mass was generated and coefficients were calculated in the derivation cohort. There was an agreement between muscle mass calculated by the novel equation and measured by DXA in both the derivation and validation cohort (P < .001, adjusted R2 = 0.829, beta = 0.95, P < .001, adjusted R2 = 0.856, beta = 1.03, respectively). CONCLUSION: The new equation based on serum creatinine and cystatin C levels can be used to estimate total-body muscle mass. PMID- 26849843 TI - Identification of new candidate drugs for lung cancer using chemical-chemical interactions, chemical-protein interactions and a K-means clustering algorithm. AB - Lung cancer, characterized by uncontrolled cell growth in the lung tissue, is the leading cause of global cancer deaths. Until now, effective treatment of this disease is limited. Many synthetic compounds have emerged with the advancement of combinatorial chemistry. Identification of effective lung cancer candidate drug compounds among them is a great challenge. Thus, it is necessary to build effective computational methods that can assist us in selecting for potential lung cancer drug compounds. In this study, a computational method was proposed to tackle this problem. The chemical-chemical interactions and chemical-protein interactions were utilized to select candidate drug compounds that have close associations with approved lung cancer drugs and lung cancer-related genes. A permutation test and K-means clustering algorithm were employed to exclude candidate drugs with low possibilities to treat lung cancer. The final analysis suggests that the remaining drug compounds have potential anti-lung cancer activities and most of them have structural dissimilarity with approved drugs for lung cancer. PMID- 26849845 TI - Adventures in Chemistry and in Information Technology: Using Chemistry Skill to Finance Partnership with Computers. PMID- 26849846 TI - Quasi-Continuous Wave Near-Infrared Excitation of Upconversion Nanoparticles for Optogenetic Manipulation of C. elegans. AB - Optogenetics is an emerging powerful tool to investigate workings of the nervous system. However, the use of low tissue penetrating visible light limits its therapeutic potential. Employing deep penetrating near-infrared (NIR) light for optogenetics would be beneficial but it cannot be used directly. This issue can be tackled with upconversion nanoparticles (UCNs) acting as nanotransducers emitting at shorter wavelengths extending to the UV range upon NIR light excitation. Although attractive, implementation of such NIR-optogenetics is hindered by the low UCN emission intensity that necessitates high NIR excitation intensities, resulting in overheating issues. A novel quasi-continuous wave (quasi-CW) excitation approach is developed that significantly enhances multiphoton emissions from UCNs, and for the first time NIR light-triggered optogenetic manipulations are implemented in vitro and in C. elegans. The approach developed here enables the activation of channelrhodopsin-2 with a significantly lower excitation power and UCN concentration along with negligible phototoxicity as seen with CW excitation, paving the way for therapeutic optogenetics. PMID- 26849844 TI - Exploratory Biomarker Study of the Triple Reuptake Inhibitor SEP-432 Compared to the Dual Reuptake Inhibitor Duloxetine in Healthy Normal Subjects. AB - INTRODUCTION: SEP-432 is a triple monoamine reuptake inhibitor of norepinephrine (NE), serotonin (5-HT), and dopamine (DA), based on in vitro binding studies. We sought evidence that SEP-432 engages these monoamine systems by measuring concentrations of monoamines and/or their main metabolites in cerebrospinal fluid (CSF) and plasma and comparing results to duloxetine, a dual reuptake inhibitor of NE and 5-HT. METHODS: Eighteen healthy normal subjects received either SEP-432 (300 mg/day), duloxetine (60 mg/day), or placebo for 14 days in-clinic (double blind) with CSF and plasma collections at baseline (single lumbar puncture) and Day 14 (24-h CSF and plasma collection). Concentrations of monoamines and their metabolites, as well as pharmacokinetic concentrations of SEP-432 and metabolite, were quantified by liquid chromatography-tandem mass spectrometry. RESULTS: Compared to placebo in the Day 14 area under the curve 24-h (AUC0-24 h ) analysis, SEP-432 significantly (P < 0.05) decreased the NE metabolite dihydroxyphenylglycol (DHPG) in CSF and plasma, decreased 5-HT in plasma, and did not affect DA metabolites, while duloxetine had significant effects on DHPG and 5 HT. Time-matched baseline to Day 14 biomarker comparisons confirmed these findings. CONCLUSION: CSF monoamine biomarkers confirmed central NET activity for SEP-432 and duloxetine's dual reuptake inhibition. PMID- 26849849 TI - Fall prevention in postmenopausal women: the role of Pilates exercise training. AB - Falls and fall-related injuries are a major public health concern for postmenopausal women. Fear of falling, impairments in gait and postural control, and changes in body composition have been identified as important risk factors for falling. Physical exercise is an important tool in fall prevention and management. The Pilates method is a non-impact activity that can be adapted to different physical conditions and health status and is recommended for various populations. In postmenopausal women, it has been deemed an effective way to improve some fall-related physical and psychological aspects, such as postural and dynamic balance. In addition, some physical capacities, such as flexibility, personal autonomy, mobility, and functional ability have also shown to benefit from Pilates interventions involving women in their second half of life, as well as certain psychological aspects including fear of falling, depressive status, and quality of life. Pilates exercise has shown effectively to prevent falls in postmenopausal women by improving their balance, physical and psychological functioning, and independence. Nevertheless, further studies are needed to demonstrate its validity in different clinical situations. PMID- 26849847 TI - The Replisome-Coupled E3 Ubiquitin Ligase Rtt101Mms22 Counteracts Mrc1 Function to Tolerate Genotoxic Stress. AB - Faithful DNA replication and repair requires the activity of cullin 4-based E3 ubiquitin ligases (CRL4), but the underlying mechanisms remain poorly understood. The budding yeast Cul4 homologue, Rtt101, in complex with the linker Mms1 and the putative substrate adaptor Mms22 promotes progression of replication forks through damaged DNA. Here we characterized the interactome of Mms22 and found that the Rtt101(Mms22) ligase associates with the replisome progression complex during S-phase via the amino-terminal WD40 domain of Ctf4. Moreover, genetic screening for suppressors of the genotoxic sensitivity of rtt101Delta cells identified a cluster of replication proteins, among them a component of the fork protection complex, Mrc1. In contrast to rtt101Delta and mms22Delta cells, mrc1Delta rtt101Delta and mrc1Delta mms22Delta double mutants complete DNA replication upon replication stress by facilitating the repair/restart of stalled replication forks using a Rad52-dependent mechanism. Our results suggest that the Rtt101(Mms22) E3 ligase does not induce Mrc1 degradation, but specifically counteracts Mrc1's replicative function, possibly by modulating its interaction with the CMG (Cdc45-MCM-GINS) complex at stalled forks. PMID- 26849850 TI - Ochratoxin A and T-2 Toxin Induce Clonogenicity and Cell Migration in Human Colon Carcinoma and Fetal Lung Fibroblast Cell Lines. AB - T-2 toxin and Ochratoxin A (OTA) are toxic secondary metabolites produced by various fungi, and together they contaminate feedstuffs worldwide. T-2 toxin and OTA may exert carcinogenic action in rodent. Despite the various in vivo experiments, carcinogenicity of these two mycotoxins has not yet been proven for human. In this current study, we proposed to investigate, in Human colon carcinoma cells and fetal lung fibroblast-like cells transfected with MYC, the effect of T-2 toxin and OTA on cell clonogenicity and cell migration. Results of the present investigation showed that T2-toxin as well as OTA has an important clonogenic effect in all cell lines, suggesting that these mycotoxins could promote the transcription of c-myc gene. Furthermore, T-2 toxin and OTA enhanced the migration effect of HCT116 cells at very low concentrations, proposing that these mycotoxins may exhibit carcinogenesis-like properties in the studied cells. PMID- 26849851 TI - Novel therapies for severe dyslipidemia originating from human genetics. AB - PURPOSE OF REVIEW: Novel therapies for severe dyslipidemia target a wide range of unmet medical needs: severe familial hypercholesterolemia, severe hypertriglyceridemia and chylomicronemia, elevated lipoprotein (a), lipodystrophies, high-density lipoprotein particle diseases, lysosomal acid lipase deficiency and storage diseases, nonalcoholic fatty liver disease and others. The purpose of this review is to describe the contribution of human genetics to the development of therapeutic approaches targeting severe dyslipidemia. RECENT FINDINGS: Recent advances in human genetics and the identification of rare genetic variants having strong effects on disease risk not only accelerated the development of therapies for severe dyslipidemia, they also revealed new pathways, genes and mechanisms of health, disease or drug response, and facilitated molecular diagnosis, which may prove essential as the authorized use of some of these novel drugs is limited to specific conditions. In addition, the dissection of the gene and cell machinery gave rise to new technologies, gene based therapies and biodrugs covering a broad range of novel agents currently available or in clinical development to treat severe lipid disorders. SUMMARY: Several novel therapies are recently available or under development to treat severe dyslipidemia and associated risk stem directly from genetic research. Altogether, these therapies target a broad variety of severe dyslipidemia pathways or mechanisms and illustrate that clinical lipidology has now entered the era of precision medicine. PMID- 26849852 TI - Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi. AB - Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 MUM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani infected human macrophages with a low IC50 value of 0.06 MUM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 MUM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease. PMID- 26849855 TI - Psychosis following traumatic brain injury and cannabis use in late adolescence. AB - BACKGROUND: Both cannabis and traumatic brain injury (TBI) pose risks on the developing brain, including a potential increased vulnerability for developing psychosis. Recent reports detail an upward trend in both adolescent cannabis use and the concentration of THC, the most potent psychoactive component in cannabis. Similarly, it is estimated that 1.7 million Americans incur a TBI each year. Previously trivialized as a minor nuisance, attitudes towards TBIs are changing as researchers and the public recognize TBIs' possible long-lasting sequelae. CASE REPORT: Two cases are presented of adolescent patients with histories of TBI and self-reported heavy, recreational cannabis use who developed symptoms of psychosis. DISCUSSION: Similar neuronal signaling pathways involved in cannabis ingestion and TBI recovery, specifically CB1 receptors of the endocannabinoid system, as well as the allostatic load model provide context for the two presented cases. Given the cases and theories presented, we believe that cannabis use may act as a neurological stressor and risk factor for psychosis outweighing its possible benefits as a therapeutic solution for pain in late adolescent and young adult populations. SIGNIFICANCE: The presented cases provide further support for the compounded risk of developing psychosis following TBI and cannabis use. PMID- 26849853 TI - Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study. AB - We report a phase II study to evaluate the efficacy and toxicity of abbreviated immunochemotherapy followed by (90) Y Ibritumomab tiuxetan ((90) Y-IT) in patients with recurrent follicular lymphoma. Of the 52 patients enrolled, 50 were treated with three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisolone), followed by (90) Y-IT regimen (15 MBq/kg, maximum 1200 MBq) preceded by two infusions of 250 mg/m(2) rituximab. The overall response rate was 98% with complete response (CR) 30% and partial response (PR) 68%. 18 patients with a PR following chemotherapy improved to a CR following (90) Y-IT: a conversion rate of 40%. Seven patients with PR following (90) Y-IT subsequently improved to a CR 12-18 months later, leading to an overall CR rate of 44%. With a median follow-up of 5 years, median progression-free survival was 23.1 months and overall survival was 77.5% at 5 years. High trough serum rituximab levels (median 112 MUg/ml; range 52-241) were attained after four doses of rituximab, prior to (90) Y-IT; this was not found to influence response rates. The treatment was well tolerated with few (13.5%) grade 3 or 4 infective episodes and manageable haematological toxicity. Abbreviated immunochemotherapy followed by (90) Y-IT is an effective and well-tolerated treatment in recurrent follicular lymphoma patients previously exposed to rituximab. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00637832. PMID- 26849856 TI - Do Social Workers Apply "Love Thy Neighbor as Thyself" to Gay, Lesbian, Bisexual, and Transpersons in the South? AB - Across the United States there has been a spate of legislative bills and initiatives that blatantly stigmatize and discriminate against the lesbian, gay, bisexual, and transgender (LGBT) community. This study was a cross-sectional, exploratory survey designed to measure the attitudes, perceptions, and behaviors of Tennessee social workers and future social workers toward the LGBT population and toward proposed discriminatory legislation. A 3-way factorial ANOVA investigated the effects of political affiliation, religious affiliation, and social contact on the dependent measures. Significant main effects were found. Self-reported political affiliation was found to be the most important factor predicting LGBT acceptance and LGBT respect among this sample. PMID- 26849857 TI - Stainless Steel Mesh-Supported NiS Nanosheet Array as Highly Efficient Catalyst for Oxygen Evolution Reaction. AB - Nickel(II) sulfide (NiS) nanosheets with a thickness of 10 nm and a size of 200 nm were facilely grown on stainless steel (SLS) meshes via a one-pot hydrothermal method. This unique construction renders an excellent electrical contact between the porous film of active NiS sheets and the highly conductive substrate, which exhibits a superior catalytic activity toward oxygen evolution reaction (OER). The NiS@SLS electrocatalyst exhibits an unusually low overpotential of 297 mV (i.e., 1.524 V vs RHE) at a current density of 11 mA.cm(-2), and an extra small Tafel slope of only 47 mV.dec(-1) proves an even more competitive performance at high to very high current densities. This performance compares very favorably to other Ni-based catalysts and even to the precious state-of-the-art IrO2 or RuO2 catalyst. PMID- 26849858 TI - Novel Foot Progression Angle Algorithm Estimation via Foot-Worn, Magneto-Inertial Sensing. AB - OBJECTIVE: The foot progression angle (FPA) is an important clinical measurement but currently can only be computed while walking in a laboratory with a marker based motion capture system. This paper proposes a novel FPA estimation algorithm based on a single integrated sensor unit, consisting of an accelerometer, gyroscope, and magnetometer, worn on the foot. METHODS: The algorithm introduces a real-time heading vector with a complementary filter and utilizes a gradient descent method and zero-velocity update correction. Validation testing was performed by comparing FPA estimation from the wearable sensor with the standard FPAs computed from a marker-based motion capture system. Subjects performed nine walking trials of 2.5 min each on a treadmill. During each trial, subjects walked at one speed out of three options (1.0, 1.2, and 1.4 m/s) and walked with one gait pattern out of three options (normal, toe-in, and toe-out). RESULTS: The algorithm estimated FPA to within 0.2 degrees of error or less for each walking conditions. CONCLUSION: A novel FPA algorithm has been introduced and described based on a single foot-worn sensor unit, and validation testing showed that FPA estimation was accurate for different walking speeds and foot angles. SIGNIFICANCE: This study enables future wearable systems gait research to assess or train walking patterns outside a laboratory setting in natural walking environments. PMID- 26849859 TI - Automatic Lumbar Spondylolisthesis Measurement in CT Images. AB - Lumbar spondylolisthesis is one of the most common spinal diseases. It is caused by the anterior shift of a lumbar vertebrae relative to subjacent vertebrae. In current clinical practices, staging of spondylolisthesis is often conducted in a qualitative way. Although meyerding grading opens the door to stage spondylolisthesis in a more quantitative way, it relies on the manual measurement, which is time consuming and irreproducible. Thus, an automatic measurement algorithm becomes desirable for spondylolisthesis diagnosis and staging. However, there are two challenges. 1) Accurate detection of the most anterior and posterior points on the superior and inferior surfaces of each lumbar vertebrae. Due to the small size of the vertebrae, slight errors of detection may lead to significant measurement errors, hence, wrong disease stages. 2) Automatic localize and label each lumbar vertebrae is required to provide the semantic meaning of the measurement. It is difficult since different lumbar vertebraes have high similarity of both shape and image appearance. To resolve these challenges, a new auto measurement framework is proposed with two major contributions: First, a learning based spine labeling method that integrates both the image appearance and spine geometry information is designed to detect lumbar vertebrae. Second, a hierarchical method using both the population information from atlases and domain-specific information in the target image is proposed for most anterior and posterior points positioning. Validated on 258 CT spondylolisthesis patients, our method shows very similar results to manual measurements by radiologists and significantly increases the measurement efficiency. PMID- 26849860 TI - MultiVCRank With Applications to Image Retrieval. AB - In this paper, we propose and develop a multi-visual-concept ranking (MultiVCRank) scheme for image retrieval. The key idea is that an image can be represented by several visual concepts, and a hypergraph is built based on visual concepts as hyperedges, where each edge contains images as vertices to share a specific visual concept. In the constructed hypergraph, the weight between two vertices in a hyperedge is incorporated, and it can be measured by their affinity in the corresponding visual concept. A ranking scheme is designed to compute the association scores of images and the relevance scores of visual concepts by employing input query vectors to handle image retrieval. In the scheme, the association and relevance scores are determined by an iterative method to solve limiting probabilities of a multi-dimensional Markov chain arising from the constructed hypergraph. The convergence analysis of the iteration method is studied and analyzed. Moreover, a learning algorithm is also proposed to set the parameters in the scheme, which makes it simple to use. Experimental results on the MSRC, Corel, and Caltech256 data sets have demonstrated the effectiveness of the proposed method. In the comparison, we find that the retrieval performance of MultiVCRank is substantially better than those of HypergraphRank, ManifoldRank, TOPHITS, and RankSVM. PMID- 26849861 TI - Category Specific Dictionary Learning for Attribute Specific Feature Selection. AB - Attributes, as mid-level features, have demonstrated great potential in visual recognition tasks due to their excellent propagation capability through different categories. However, existing attribute learning methods are prone to learning the correlated attributes. To discover the genuine attribute specific features, many feature selection methods have been proposed. However, these feature selection methods are implemented at the level of raw features that might be very noisy, and these methods usually fail to consider the structural information in the feature space. To address this issue, in this paper, we propose a label constrained dictionary learning approach combined with a multilayer filter. The feature selection is implemented at dictionary level, which can better preserve the structural information. The label constrained dictionary learning suppresses the intra-class noise by encouraging the sparse representations of intra-class samples to lie close to their center. A multilayer filter is developed to discover the representative and robust attribute specific bases. The attribute specific bases are only shared among the positive samples or the negative samples. The experiments on the challenging Animals with Attributes data set and the SUN attribute data set demonstrate the effectiveness of our proposed method. PMID- 26849862 TI - Blind Super Resolution of Real-Life Video Sequences. AB - Super resolution (SR) for real-life video sequences is a challenging problem due to complex nature of the motion fields. In this paper, a novel blind SR method is proposed to improve the spatial resolution of video sequences, while the overall point spread function of the imaging system, motion fields, and noise statistics are unknown. To estimate the blur(s), first, a nonuniform interpolation SR method is utilized to upsample the frames, and then, the blur(s) is(are) estimated through a multi-scale process. The blur estimation process is initially performed on a few emphasized edges and gradually on more edges as the iterations continue. Also for faster convergence, the blur is estimated in the filter domain rather than the pixel domain. The high-resolution frames are estimated using a cost function that has the fidelity and regularization terms of type Huber-Markov random field to preserve edges and fine details. The fidelity term is adaptively weighted at each iteration using a masking operation to suppress artifacts due to inaccurate motions. Very promising results are obtained for real-life videos containing detailed structures, complex motions, fast-moving objects, deformable regions, or severe brightness changes. The proposed method outperforms the state of the art in all performed experiments through both subjective and objective evaluations. The results are available online at http://lyle.smu.edu/~rajand/Video_SR/. PMID- 26849864 TI - Robust All-in-Focus Super-Resolution for Focal Stack Photography. AB - We present an unconventional image super-resolution algorithm targeting focal stack images. Contrary to previous works, which align multiple images with sub pixel accuracy for image super-resolution, we analyze the correlation among the differently focused narrow depth-of-field images in a focal stack to infer high resolution details for image super-resolution. In order to accurately model the defocus kernels at different depths, we use a cubic interpolation to parameterize the projection of defocus kernels, and apply the radon transform to accurately reconstruct the defocus kernels at arbitrary depth. In the image super resolution, we utilize the multi-image deconvolution method with a l1 -norm regularization to suppress noise and ringing artifacts. We have also extended the depth-of-field of our inputs to produce an all-in-focus super-resolution image. The effectiveness of our algorithm is demonstrated with the quantitative analysis using synthetic examples and the qualitative analysis using real-world examples. PMID- 26849863 TI - Framelet-Based Sparse Unmixing of Hyperspectral Images. AB - Spectral unmixing aims at estimating the proportions (abundances) of pure spectrums (endmembers) in each mixed pixel of hyperspectral data. Recently, a semi-supervised approach, which takes the spectral library as prior knowledge, has been attracting much attention in unmixing. In this paper, we propose a new semi-supervised unmixing model, termed framelet-based sparse unmixing (FSU), which promotes the abundance sparsity in framelet domain and discriminates the approximation and detail components of hyperspectral data after framelet decomposition. Due to the advantages of the framelet representations, e.g., images have good sparse approximations in framelet domain, and most of the additive noises are included in the detail coefficients, the FSU model has a better antinoise capability, and accordingly leads to more desirable unmixing performance. The existence and uniqueness of the minimizer of the FSU model are then discussed, and the split Bregman algorithm and its convergence property are presented to obtain the minimal solution. Experimental results on both simulated data and real data demonstrate that the FSU model generally performs better than the compared methods. PMID- 26849865 TI - The Lattice-Based Screen Set: A Square N -Color All-Orders Moire-Free Screen Set. AB - Periodic clustered-dot screens are widely used for electrophotographic printers due to their print stability. However, moire is a ubiquitous problem that arises in color printing due to the beating together of the clustered-dot, periodic halftone patterns that are used to represent different colorants. The traditional solution in the graphic arts and printing industry is to rotate identical square screens to angles that are maximally separated from each other. However, the effectiveness of this approach is limited when printing with more than four colorants, i.e., N -color printing, where N > 4 . Moreover, accurately achieving the angles that have maximum angular separation requires a very high-resolution plate writer, as is used in commercial offset printing. Commercially available high-end digital printers cannot achieve this resolution. In this paper, we propose a systematic way to design color screen sets for periodic, clustered-dot screens that offer more explicit control of the moire properties of the resulting screens when used in color printing. We develop a principled approach for the moire-free screen design that is called lattice-based screen design. The basic concept behind our approach is the creation of the screen set on a 2D lattice in the frequency domain, and then picking each fundamental frequency vector of the individual colorant planes in the created spectral lattice according to the desired properties. The lattice-based screen design offers more flexibility in designing N -color screen sets with different halftone geometries, and all of them are guaranteed to be all-orders moire-free. We demonstrate the efficacy of our proposed method by introducing several new screen designs, and a comparison with published screen designs. PMID- 26849866 TI - Learn Sparse Dictionaries for Edit Propagation. AB - With the increasing availability of high-resolution images, videos, and 3D models, the demand for scalable large data processing techniques increases. We introduce a method of sparse dictionary learning for edit propagation of large input data. Previous approaches for edit propagation typically employ a global optimization over the whole set of pixels (or vertexes), incurring a prohibitively high memory and time-consumption for large input data. Rather than propagating an edit pixel by pixel, we follow the principle of sparse representation to obtain a representative and compact dictionary and perform edit propagation on the dictionary instead. The sparse dictionary provides an intrinsic basis for input data, and the coding coefficients capture the linear relationship between all pixels and the dictionary atoms. The learned dictionary is then optimized by a novel scheme, which maximizes the Kullback-Leibler divergence between each atom pair to remove redundant atoms. To enable local edit propagation for images or videos with similar appearance, a dictionary learning strategy is proposed by considering range constraint to better account for the global distribution of pixels in their feature space. We show several applications of the sparsity-based edit propagation, including video recoloring, theme editing, and seamless cloning, operating on both color and texture features. Our approach can also be applied to computer graphics tasks, such as 3D surface deformation. We demonstrate that with an atom-to-pixel ratio in the order of 0.01% signifying a significant reduction on memory consumption, our method still maintains a high degree of visual fidelity. PMID- 26849867 TI - Fourier Spectral Filter Array for Optimal Multispectral Imaging. AB - Limitations to existing multispectral imaging modalities include speed, cost, range, spatial resolution, and application-specific system designs that lack versatility of the hyperspectral imaging modalities. In this paper, we propose a novel general-purpose single-shot passive multispectral imaging modality. Central to this design is a new type of spectral filter array (SFA) based not on the notion of spatially multiplexing narrowband filters, but instead aimed at enabling single-shot Fourier transform spectroscopy. We refer to this new SFA pattern as Fourier SFA, and we prove that this design solves the problem of optimally sampling the hyperspectral image data. PMID- 26849868 TI - Biomechanical and Physiological Evaluation of Multi-Joint Assistance With Soft Exosuits. AB - To understand the effects of soft exosuits on human loaded walking, we developed a reconfigurable multi-joint actuation platform that can provide synchronized forces to the ankle and hip joints. Two different assistive strategies were evaluated on eight subjects walking on a treadmill at a speed of 1.25 m/s with a 23.8 kg backpack: 1) hip extension assistance and 2) multi-joint assistance (hip extension, ankle plantarflexion and hip flexion). Results show that the exosuit introduces minimum changes to kinematics and reduces biological joint moments. A reduction trend in muscular activity was observed for both conditions. On average, the exosuit reduced the metabolic cost of walking by 0.21 +/-0.04 and 0.67 +/-0.09 W/kg for hip extension assistance and multi-joint assistance respectively, which is equivalent to an average metabolic reduction of 4.6% and 14.6%, demonstrating that soft exosuits can effectively improve human walking efficiency during load carriage without affecting natural walking gait. Moreover, it indicates that actuating multiple joints with soft exosuits provides a significant benefit to muscular activity and metabolic cost compared to actuating single joint. PMID- 26849869 TI - Endogenous Sensory Discrimination and Selection by a Fast Brain Switch for a High Transfer Rate Brain-Computer Interface. AB - In this study, we present a novel multi-class brain-computer interface (BCI) for communication and control. In this system, the information processing is shared by the algorithm (computer) and the user (human). Specifically, an electro tactile cycle was presented to the user, providing the choice (class) by delivering timely sensory input. The user discriminated these choices by his/her endogenous sensory ability and selected the desired choice with an intuitive motor task. This selection was detected by a fast brain switch based on real-time detection of movement-related cortical potentials from scalp EEG. We demonstrated the feasibility of such a system with a four-class BCI, yielding a true positive rate of ~ 80% and ~ 70%, and an information transfer rate of ~ 7 bits/min and ~ 5 bits/min, for the movement and imagination selection command, respectively. Furthermore, when the system was extended to eight classes, the throughput of the system was improved, demonstrating the capability of accommodating a large number of classes. Combining the endogenous sensory discrimination with the fast brain switch, the proposed system could be an effective, multi-class, gaze-independent BCI system for communication and control applications. PMID- 26849870 TI - The Time-Varying Networks in P300: A Task-Evoked EEG Study. AB - P300 is an important event-related potential that can be elicited by external visual, auditory, and somatosensory stimuli. Various cognition-related brain functions (i.e., attention, intelligence, and working memory) and multiple brain regions (i.e., prefrontal, frontal, and parietal) are reported to be involved in the elicitation of P300. However, these studies do not investigate the instant interactions across the neural cortices from the hierarchy of milliseconds. Importantly, time-varying network analysis among these brain regions can uncover the detailed and dynamic information processing in the corresponding cognition process. In the current study, we utilize the adaptive directed transfer function to construct the time-varying networks of P300 based on scalp electroencephalographs, investigating the time-varying information processing in P300 that can depict the deeper neural mechanism of P300 from the network. Our analysis found that different stages of P300 evoked different brain networks, i.e., the center area performs as the central source during the decision process stage, while the source region is transferred to the right prefrontal cortex (rPFC) in the neuronal response stage. Moreover, during the neuronal response stage, the directed information that flows from the rPFC to the parietal cortex are remarkably important. These findings indicate that the two brain hemispheres exhibit asymmetrical functions in processing related information for different P300 stages, and this work may provide new evidence for our better understanding of the neural mechanism of P300 generation. PMID- 26849871 TI - A Study of Domain Adaptation Classifiers Derived From Logistic Regression for the Task of Splice Site Prediction. AB - Supervised classifiers are highly dependent on abundant labeled training data. Alternatives for addressing the lack of labeled data include: labeling data (but this is costly and time consuming); training classifiers with abundant data from another domain (however, the classification accuracy usually decreases as the distance between domains increases); or complementing the limited labeled data with abundant unlabeled data from the same domain and learning semi-supervised classifiers (but the unlabeled data can mislead the classifier). A better alternative is to use both the abundant labeled data from a source domain, the limited labeled data and optionally the unlabeled data from the target domain to train classifiers in a domain adaptation setting. We propose two such classifiers, based on logistic regression, and evaluate them for the task of splice site prediction-a difficult and essential step in gene prediction. Our classifiers achieved high accuracy, with highest areas under the precision-recall curve between 50.83% and 82.61%. PMID- 26849872 TI - Treatment of the Partial Hand Amputation: An Engineering Perspective. AB - Partial hand amputation is perhaps the most frequent amputation level, worldwide. Although its annual incidence in western countries is roughly 1:18 000 inhabitants, the treatments of partial hand amputations have modestly progressed so far. We have identified three main limitation factors to this progress: 1) the wide range of anatomical and functional presentations, which makes difficult to find standardized and scalable solutions; 2) the technological complexity in replacing the motor and sensory function of a lost digit in the size of a digit; and 3) the fact that a partial hand can be functionally successful mostly when it restores a lost opposition movement, i.e., the ability to oppose the thumb against the fingers while providing enough grasping force and aperture width. This review presents an overview of the existing surgical and technological solutions for treating partial hand amputations, and is specifically targeted to (biomedical) engineers. We critically highlighted the advantages, limitations, and open challenges. Remarkably, current fitting procedures rely on manual approaches by skilled prosthetic technicians rather than on modern engineering methods. Hence, the objective of this study is to comprehensively but concisely overview the field in order to inspire engineers to develop new systems and procedures able to address current open issues. PMID- 26849873 TI - Learning in Variable-Dimensional Spaces. AB - This paper proposes a unified approach to learning in environments in which patterns can be represented in variable-dimension domains, which nicely includes the case in which there are missing features. The proposal is based on the representation of the environment by pointwise constraints that are shown to model naturally pattern relationships that come out in problems of information retrieval, computer vision, and related fields. The given interpretation of learning leads to capturing the truly different aspects of similarity coming from the content at different dimensions and the pattern links. It turns out that functions that process real-valued features and functions that operate on symbolic entities are learned within a unified framework of regularization that can also be expressed using the kernel machines mathematical and algorithmic apparatus. Interestingly, in the extreme cases in which only the content or only the links are available, our theory returns classic kernel machines or graph regularization, respectively. We show experimental results that provide clear evidence of the remarkable improvements that are obtained when both types of similarities are exploited on artificial and real-world benchmarks. PMID- 26849874 TI - Adaptive Method for Nonsmooth Nonnegative Matrix Factorization. AB - Nonnegative matrix factorization (NMF) is an emerging tool for meaningful low rank matrix representation. In NMF, explicit constraints are usually required, such that NMF generates desired products (or factorizations), especially when the products have significant sparseness features. It is known that the ability of NMF in learning sparse representation can be improved by embedding a smoothness factor between the products. Motivated by this result, we propose an adaptive nonsmooth NMF (Ans-NMF) method in this paper. In our method, the embedded factor is obtained by using a data-related approach, so it matches well with the underlying products, implying a superior faithfulness of the representations. Besides, due to the usage of an adaptive selection scheme to this factor, the sparseness of the products can be separately constrained, leading to wider applicability and interpretability. Furthermore, since the adaptive selection scheme is processed through solving a series of typical linear programming problems, it can be easily implemented. Simulations using computer-generated data and real-world data show the advantages of the proposed Ans-NMF method over the state-of-the-art methods. PMID- 26849875 TI - Symmetric Complex-Valued Hopfield Neural Networks. AB - Complex-valued neural networks, which are extensions of ordinary neural networks, have been studied as interesting models by many researchers. Especially, complex valued Hopfield neural networks (CHNNs) have been used to process multilevel data, such as gray-scale images. CHNNs with Hermitian connection weights always converge using asynchronous update. The noise tolerance of CHNNs deteriorates extremely as the resolution increases. Noise tolerance is one of the most controversial problems for CHNNs. It is known that rotational invariance reduces noise tolerance. In this brief, we propose symmetric CHNNs (SCHNNs), which have symmetric connection weights. We define their energy function and prove that the SCHNNs always converge. In addition, we show that the SCHNNs improve noise tolerance through computer simulations and explain this improvement from the standpoint of rotational invariance. PMID- 26849876 TI - EFLM WG-Preanalytical phase opinion paper: local validation of blood collection tubes in clinical laboratories. AB - The selection or procurement of blood collection devices in healthcare facilities is often an underestimated issue. This is probably due to different factors including the lack of knowledge of policymakers, hospital administrators and even laboratory managers about the importance of preanalytical quality and phlebotomy process, as well as to the absence of reliable guidelines or recommendations on how to precisely assess the quality of blood collection devices around the globe. With the awareness that a gap remains between manufacturers' and local validation of blood collection devices, the Working Group for Preanalytical Phase (WG-PRE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has drafted a consensus document aimed to provide a set of essential requisites, technical criteria (e.g. presence of physical defects, malfunctioning, safety problems) and clinical issues for supporting laboratory professionals in organization blood collection tubes tenders and validating new devices before local routine implementation. The laboratory professionals should also make sure that the tenders accurately and strictly define the responsibilities for validation experiments and the potential consequences in the case the validation outcome shows that tubes due not fulfill the expectations. PMID- 26849877 TI - Erratum to: Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study. PMID- 26849878 TI - Anti-inflammatory function of 4-tert-butylphenyl salicylate through down regulation of the NF-kappa B pathway. AB - The salicylic acid derivative 4-tert-butylphenyl salicylate (4-TBPS) possesses anti-inflammatory activity. We demonstrated this and elucidated the mechanisms involved by using the lipopolysaccharide-stimulated Raw 264.7 mouse macrophage model. The 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, western blot, enzyme-linked immunosorbent assay, and reverse transcriptase polymerase chain reaction were performed to explore 4-TBPS anti-inflammatory activity. We found that 4-TBPS decreased nitric oxide production without cytotoxic effects on macrophages and reduced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in a dose-dependent manner. Additionally, mRNA expressions of iNOS and COX-2 significantly reduced, with concentrations between 1 and 15 ug/ml. Furthermore, 4-TBPS significantly inhibited the production of pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin- (IL)-1beta, and IL-6. Moreover, mRNA gene expression of TNF-alpha, IL-1beta, and IL-6 was attenuated in a dose-dependent manner. 4-TBPS potently inhibited translocation of nuclear factor-kappaB (NF kappaB) into the nucleus by degrading IkappaB kinase (IkappaBalpha) following its phosphorylation, thereby causing NF-kappaB to remain inactive. Collectively, our data indicate that 4-TBPS significantly (p < 0.01) targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, TNF-alpha, IL-1beta, and IL-6 through downregulation of the NF-kappaB pathway. This indicates that 4-TBPS may have therapeutic potential in inflammatory disorders. PMID- 26849879 TI - Geographic divergence in upper thermal limits across insect life stages: does behavior matter? AB - Insects with complex life cycles vary in size, mobility, and thermal ecology across life stages. We examine how differences in the capacity for thermoregulatory behavior influence geographic differences in physiological heat tolerance among egg and adult Colias butterflies. Colias adults exhibit differences in morphology (wing melanin and thoracic setal length) along spatial gradients, whereas eggs are morphologically indistinguishable. Here we compare Colias eriphyle eggs and adults from two elevations and Colias meadii from a high elevation. Hatching success and egg development time of C. eriphyle eggs did not differ significantly with the elevation of origin. Egg survival declined in response to heat-shock temperatures above 38-40 degrees C and egg development time was shortest at intermediate heat-shock temperatures of 33-38 degrees C. Laboratory experiments with adults showed survival in response to heat shock was significantly greater for Colias from higher than from lower elevation sites. Common-garden experiments at the low-elevation field site showed that C. meadii adults initiated heat-avoidance and over-heating behaviors significantly earlier in the day than C. eriphyle. Our study demonstrates the importance of examining thermal tolerances across life stages. Our findings are inconsistent with the hypothesis that thermoregulatory behavior inhibits the geographic divergence of physiological traits in mobile stages, and suggest that sessile stages may evolve similar heat tolerances in different environments due to microclimatic variability or evolutionary constraints. PMID- 26849880 TI - 'Candidatus Phytoplasma cirsii', a novel taxon from creeping thistle [Cirsium arvense (L.) Scop]. AB - Creeping thistle [Cirsium arvense (L.) Scop.] and dahlia (Dahlia sp.) plants showing typical symptoms of phytoplasma infection including yellowing, stunting, inflorescence and proliferation, were sampled; the presence of phytoplasma was confirmed by standard PCR using universal primers. RFLP analysis allowed classification of the detected phytoplasma strains CirYS, CirYS1 and DahlP within the 16SrXI group, the unique restriction profile F2nR2 fragment obtained in silico by iPhyClassifier indicated that they belong to the new 16SrXI-E subgroup. Genetic analysis of the 16S rRNA gene revealed that the studied strains shared less than 97.5% similarity with all of the previously described 'Candidatus Phytoplasma' species. The closest relatives are 'Candidatus Phytoplasma cynodontis' and 'Candidatus Phytoplasma oryzae' with 96.8% and 96.6% similarity. All strains studied bear three specific regions in the 16S rRNA gene, discriminating them from the other phytoplasma species. Phylogenetic analysis of the 16S rRNA and secA genes confirmed this specificity, as the creeping thistle and dahlia phytoplasma strains clustered in a distinguishable lineage group. The uniqueness of the genetic analysis agrees with the biological characterization of the studied phytoplasma strains, their host range, and geographical distribution. The strains only infect dicotyledonous plants in Europe, contrary to their closest relatives. Based on their unique properties, it could be concluded that the studied phytoplasma strains represent a discrete group that is proposed as a novel taxon 'Candidatus Phytoplasma cirsii', with strain CirYS as a reference strain. PMID- 26849881 TI - Results of the treatment of bone metastases with modular prosthetic replacement- analysis of 67 patients. AB - BACKGROUND: Surgical treatment of long-bone metastases requires a comprehensive approach. The indications for surgery are based on the patient's general condition, type and stage of cancer, and survival time expectancy. Tumor modular endoprostheses have been increasingly used. Surgery should provide pain relief and improve the quality of life. METHODS: Between 2010 and 2013, 67 patients with malignant metastases were surgically treated with resection prostheses. We performed a retrospective analysis of the indications for the surgery, its course, the type of the prostheses used, and the implantation techniques applied. We evaluated the most important clinical parameters influencing the postoperative quality of life of the patients. RESULTS: Breast, prostate, and lung cancers are the most common primary tumors that metastasize to bones. The most common site of the lesions is the proximal femur; sporadically, they do occur in bones distal to the knee and elbow. After the surgery, all the patients could walk, most of them without crutches. The pain, rated on a VAS scale, decreased significantly, and the Karnofsky score improved. We observed that joint mobility and the strength of the muscles in the limbs allowed for normal functioning. Postoperative complications including infections and local tumor recurrences were rarely observed. CONCLUSIONS: The use of modular prostheses is an adequate method of treatment in patients with bone metastases. A radical resection of the tumor, which prevents local recurrences and loosening of implants, gives good outcomes. Reduced joint mobility resulting from muscle attachment cutting is well tolerated and concerns mainly patients that underwent operations on the humerus. PMID- 26849882 TI - Liquid PTVA: a faster and cheaper alternative for generating multi-copy clones in Pichia pastoris. AB - BACKGROUND: Multiple cognate gene copy clones have often been used in order to increase the yield of recombinant protein expression in the yeast Pichia pastoris. The method of posttransformational vector amplification (PTVA) has allowed for the efficient generation of multi-copy clones in P. pastoris. However, despite its relative ease and success, this process can be expensive and time consuming. RESULTS: We have developed a modified version of PTVA, called Liquid PTVA, which allows for faster and cheaper selection of multi-copy clones. Cultures are grown in liquid medium with only a final selection carried out on agar plates, reducing overall antibiotic usage and increasing the speed of clone amplification. In addition, it was established that starting PTVA with a single copy clone resulted in higher copy number strains for both traditional plate PTVA and liquid PTVA. Furthermore, using the Zeocin selection marker in liquid PTVA results in strains with higher growth rates, which could be beneficial for recombinant protein production processes. CONCLUSIONS: We present a methodology for creating multi-copy clones that can be achieved over 12 days instead of the traditional 45 and at approximately half the cost. PMID- 26849883 TI - Subclinical pulmonary abnormalities in childhood-onset systemic lupus erythematosus patients. AB - OBJECTIVE: The aims of this study were to analyze the pulmonary function of childhood-onset systemic lupus erythematosus (cSLE) patients and to identify possible correlations between the high-resolution computed chest tomography (HRCT) score, disease activity, disease cumulative damage, and the participants' quality of life. METHODS: Forty cSLE patients, median age: 14.1 years (range: 7.4 17.9), underwent spirometry and plethysmography. Carbon monoxide diffusing capacity (DLCO), HRCT, disease activity, disease cumulative damage, and quality of life were assessed. RESULTS: Pulmonary abnormalities were evident in 19/40 (47.5%) cSLE patients according to spirometry/DLCO. Forced expired volume in one second (FEV1%) was the parameter most affected (30%). The HRCT showed some abnormality in 22/30 patients (73%), which were minimal in 43%. Signs of airway affects were found in 50%. Twelve patients were hospitalized due to cSLE-related pulmonary complications before the study began (median discharge: 2.1 years earlier). Total lung capacity (TLC%), vital capacity (VC%), forced vital capacity (FVC%), and FEV1% were significantly lower in the group with hospitalization compared to the group without hospitalization (p = 0.0025, p = 0.0022, p = 0.0032, and p = 0.0004, respectively). Of note, DLCO was positively correlated with disease duration (r = +0.4; p = 0.01). The HRCT-score was negatively correlated with FEV1/VC (r = -0.63; p = 0.0002), FEV1 (r = -0.54; p = 0.018), FEF25%-75% (r = -0.67; p < 0.0001), and HRCT-score was positively correlated with resistance (r = +0.49; p = 0.0056). CONCLUSIONS: Almost half of patients with cSLE had subclinical pulmonary abnormalities, especially airway abnormalities. The cSLE-related pulmonary complications seem to determine long-term functional damage. PMID- 26849884 TI - Right paratracheal mass on chest X-ray: an important part of the checklist before cardiac catheterisation. PMID- 26849885 TI - Bias in military studies of mefloquine. PMID- 26849886 TI - Pertussis has low prevalence in adults with acute cough and is difficult to distinguish clinically from other causes. PMID- 26849887 TI - Waste dumps in local communities in developing countries and hidden danger to health. AB - AIM: The rapid industrialisation and urbanisation fuelled by a fast-growing population has led to the generation of a huge amount of waste in most communities in developing countries. The hidden disorders and health dangers in waste dumps are often ignored. The waste generated in local communities is usually of a mixed type consisting of domestic waste and waste from small-scale industrial activities. Among these wastes are toxic metals, lead (Pb), cadmium (Cd), arsenic (As), mercury (Hg), halogenated organic compounds, plastics, remnants of paints that are themselves mixtures of hazardous substances, hydrocarbons and petroleum product-contaminated devices. Therefore, there is the urgent need to create an awareness of the harmful health effect of toxic wastes in developing countries, especially Nigeria. METHOD: This is a review aimed at creating awareness on the hidden dangers of waste dumps to health in local communities in developing countries. Many publications in standard outlets use the following keywords: cancer, chemical toxicity, modern environmental health hazards, waste management and waste speciation in PubMed, ISI, Toxbase environmental digest, related base journals, and some standard textbooks, as well as the observation of the researcher between 1959 and 2014. RESULTS: Studies revealed the preponderance of toxic chemicals such as Pb, Cd, As and Hg in dump sites that have the risk of entering food chain and groundwater supplies, and these can give rise to endemic malnutrition and may also increase susceptibility to mutagenic substances, thereby increasing the incidence of cancer in developing countries. CONCLUSION: Industrialisation and urbanisation have brought about a change in the waste that is generated in contemporary communities in developing countries. Therefore, there is the need to embrace speciation and sound management of waste, probably including bioremediation. RECOMMENDATION: The populations in the local communities need regulatory agencies who are health educators as positive change agents. PMID- 26849888 TI - Neurological presentations of intravascular lymphoma (IVL): meta-analysis of 654 patients. AB - BACKGROUND: Patients with intravascular lymphoma (IVL) frequently have neurological signs and symptoms. Prompt diagnosis and treatment is therefore crucial for their survival. However, the spectrum of neurological presentations and their respective frequencies have not been adequately characterized. Our aim is to document the spectrum of clinical symptoms and their respective frequencies and to create a clinical framework for the prompt diagnosis of IVL. METHODS: A comprehensive meta-analysis of 654 cases of IVL published between 1957 and 2012 was performed to provide better insight into the neurological presentations of this disease. Neurologic complications were mainly divided into central nervous system (CNS) and peripheral nervous system (PNS) presentations. RESULTS: There were no differences in occurrences of CNS IVL based on gender or geographic locations (Asian Vs non-Asian). However, most patients with CNS IVL were younger than 70 years of age (p < 0.05). Our limited data do not support the treatment efficacy of methotrexate. CNS symptoms were seen in 42% of all cases. The most common CNS complications identified were cognitive impairment/dementia (60.9%), paralysis (22.2%), and seizures (13.4%). PNS complications were seen in 9.5% of cases. Out of these, muscle weakness (59.7%), neurogenic bladder (37.1%), and paresthesia (16.1%) were the most common presentations. CONCLUSIONS: CNS complications are more common among IVL patients. Out of these, dementia and seizures outnumber stroke-like presentations. PMID- 26849889 TI - Studying in the region of proximal learning reduces mind wandering. AB - Insofar as mind wandering has been linked to poor learning, finding ways to reduce the propensity to mind wander should have implications for improving learning. We investigated the possibility that studying materials at an appropriate level of difficulty with respect to the individual's capabilities that is, studying in the region of proximal learning (RPL)-might reduce mind wandering. In Experiments 1 and 2, participants were probed for their attentional state while they studied blocks of English-Spanish word pairs that were (a) easy, (b) in the RPL, or (c) difficult. We found that studying materials in the RPL was associated with reduced mind wandering. Test performance on items studied while mind wandering was also poorer. In Experiment 3, we investigated the relation between differences in participants' mastery and mind wandering. We found that high performers mind wandered more when studying the easier word pairs, whereas low performers mind wandered more when studying the difficult items. These results indicate that the RPL is specific to the individual's level of mastery and that mind wandering occurs when people are outside that region. PMID- 26849890 TI - Pro-brain natriuretic peptide (ProBNP) levels in North Indian children with Kawasaki disease. AB - The diagnosis of Kawasaki disease (KD), a common pediatric vasculitis, is based solely on clinical criteria. There is a need for a robust laboratory marker that can help differentiate KD from other acute, febrile, childhood illnesses and also to predict cardiac involvement. We conducted a cross-sectional study of 25 consecutive patients admitted with diagnosis of KD from January 2013 to April 2014 and compared them with age- and sex-matched febrile controls. We studied the serum pro-brain natriuretic peptide (ProBNP) [ProBNP and N-terminal pro-B-type natriuretic peptide (NT-ProBNP) levels], a marker of myocardial dysfunction, in children with KD in acute and convalescent phases of disease. These levels were also estimated in febrile controls for comparison. The ProBNP (ProBNP and NT ProBNP) levels were much higher in the acute phase of the KD patients compared to levels in the convalescent phase of KD (p = 0.000014). Similarly, the levels in the acute phase were higher when compared to the age- and sex-matched febrile controls (p = 0.000126). The receiver operating curve (ROC) analysis for the ProBNP levels in the acute phase of KD yielded an area under the curve of 0.954 +/- 0.034 (p < 0.000, 95 % CI 0.886-1.0). Based on ROC analysis, a cutoff of 1025 pg/mL for ProBNP levels in the acute phase of KD had 88 % sensitivity and 96 % specificity for the diagnosis of KD. A lower cut-off of 514 pg/mL yielded a 100 % sensitivity and 80 % specificity for the diagnosis of KD. The ProBNP levels were higher in those with coronary artery abnormalities (CAA) compared to those without CAA in both acute (p = 0.013) and convalescent (p = 0.045) phases. ProBNP levels may be used as a surrogate marker for the differentiation of KD from other febrile, infectious illnesses and may also predict the involvement of coronary arteries. PMID- 26849892 TI - Accurate estimation of protein/creatinine ratio on urine sample in CKD patients. PMID- 26849891 TI - Mapping health assessment questionnaire disability index (HAQ-DI) score, pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) onto the EuroQol-5D (EQ-5D) utility score with the KORean Observational study Network for Arthritis (KORONA) registry data. AB - The aim of this study was to estimate the mapping model for EuroQol-5D (EQ-5D) utility values using the health assessment questionnaire disability index (HAQ DI), pain visual analog scale (VAS), and disease activity score in 28 joints (DAS28) in a large, nationwide cohort of rheumatoid arthritis (RA) patients in Korea. The KORean Observational study Network for Arthritis (KORONA) registry data on 3557 patients with RA were used. Data were randomly divided into a modeling set (80 % of the data) and a validation set (20 % of the data). The ordinary least squares (OLS), Tobit, and two-part model methods were employed to construct a model to map to the EQ-5D index. Using a combination of HAQ-DI, pain VAS, and DAS28, four model versions were examined. To evaluate the predictive accuracy of the models, the root-mean-square error (RMSE) and mean absolute error (MAE) were calculated using the validation dataset. A model that included HAQ-DI, pain VAS, and DAS28 produced the highest adjusted R (2) as well as the lowest Akaike information criterion, RMSE, and MAE, regardless of the statistical methods used in modeling set. The mapping equation of the OLS method is given as EQ-5D = 0.95-0.21 * HAQ-DI-0.24 * pain VAS/100-0.01 * DAS28 (adjusted R (2) = 57.6 %, RMSE = 0.1654 and MAE = 0.1222). Also in the validation set, the RMSE and MAE were shown to be the smallest. The model with HAQ-DI, pain VAS, and DAS28 showed the best performance, and this mapping model enabled the estimation of an EQ-5D value for RA patients in whom utility values have not been measured. PMID- 26849893 TI - Parkinson's disease diagnosis is preceded by increased risk of falls, study finds. PMID- 26849894 TI - Should ketamine be used for the clinical treatment of depression? AB - OBJECTIVE: There has been widespread interest from the public and media in the potential of ketamine as a novel treatment for depression. This paper reviews whether current evidence supports the use of ketamine for the clinical treatment of depression. CONCLUSIONS: Clinical trials have investigated the use of intravenous ketamine for the treatment of depressive symptoms over the past 15 years. However, there remain many unanswered questions regarding its effectiveness, safety, and the route, dose and regimen for repeated administration. Experts have also raised concerns regarding ketamine's adverse effects, abuse potential and the risk of addiction. At this stage, the use of ketamine in the treatment of depression remains in the realm of research settings. PMID- 26849895 TI - Rate of community treatment orders and readmission orders following reconfiguration of community mental health services. AB - OBJECTIVES: Community treatment orders (CTOs) are a controversial practice as they extend the practice of involuntary treatment into the community. This study aimed to determine whether there was a difference in the rate of CTOs and revocation (readmission) orders following the implementation of a recovery orientated model across four adult mental health services. METHODS: A retrospective cohort study was conducted prior to and after the reconfiguration of services. Population data for those aged 15 to 65 were obtained from a census and rate rates were calculated. RESULTS: Prior to the reconfiguration, there were 893 individuals subject to a CTO and 136 of these individuals had a revocation of their CTO (i.e. were involuntarily readmitted). This represented a rate of 100.8 individuals on CTOs per 100,000 population and a rate of 15.4 revocations per 100,000 population. Following the reconfiguration, the rate of CTOs increased by 10% and there was a trend for the rate of revocation orders to have decreased by 17%. CONCLUSIONS: Rates of CTOs and readmissions varied across services and further research is warranted to identify factors associated with these increased rates. Additionally, the very high rate of CTOs in the catchment areas warrants further examination. PMID- 26849896 TI - WHO warns European countries to be on alert for Zika. PMID- 26849897 TI - beta-Catenin is important for cancer stem cell generation and tumorigenic activity in nasopharyngeal carcinoma. AB - Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors with poor prognosis and recurrence in South China. The hard eradication of NPC in clinic is predominantly due to cancer stem cells (CSCs). Increasing evidence revealed that the aberrant activation of Wnt/beta-catenin was positively correlated with the produce of CSCs. To further investigate the effect of beta catenin on CSCs and tumorigenesis in NPC, a CNE2 cell line (pLKO.1-sh-beta catenin-CNE2) with stably suppressed expression of beta-catenin was used in this study. The expressions of biomarkers in CSCs including c-myc, Nanog, Oct3/4, Sox2, EpCAM as well as adhesion-related proteins like E-cadherin and vimentin were analyzed by western blot analysis and immunofluorescent staining. The proliferation and migration abilities were investigated by MTT assay and Transwell assay, respectively. Cell cycle was analyzed by flow cytometry. Finally, xenograft was performed to determine the effect of beta-catenin on oncogenesis in vivo. Results showed that the expressions of c-myc, Nanog, Oct3/4, Sox2, and EpCAM were all decreased in pLKO.1-sh-beta-catenin-CNE2 cells. It was also found that vimentin was downregulated, while E-cadherin was upregulated. Results of MTT and Transwell assays suggested that the proliferation and migration abilities were impaired by silencing of beta-catenin, and more cells were arrested in G1 phase when compared with the control. In vivo study indicated that the tumor growth was markedly suppressed in experimental group. Based on current findings, beta-catenin may function as an essential protein for the maintenance of migration and proliferation abilities of NPC cells, and a complicated network consisting of c-myc, Nanog, Oct3/4, Sox2, EpCAM, E-cadherin, vimentin, and beta-catenin may be involved in the inherent regulation mechanisms. PMID- 26849898 TI - Host-Feeding Sources and Infection With Trypanosoma cruzi of Triatoma infestans and Triatoma eratyrusiformis (Hemiptera: Reduviidae) From the Calchaqui Valleys in Northwestern Argentina. AB - We assessed the prevalence of infection with Trypanosoma cruzi, parasite genotypes (discrete typing units, DTUs), and the host-feeding sources of domestic and peridomestic Triatoma infestans Klug and Triatoma eratyrusiformis Del Ponte in eight rural communities of the subandean Calchaqui valleys in northwestern Argentina. We sought to analyze their epidemiological role in the context of routine vector surveillance and control actions. Infection with T. cruzi was determined by optic microscopy or polymerase chain reaction (PCR) amplification of the hypervariable region of kinetoplast DNA minicircles. Parasite genotypes were identified through a multi PCR-based strategy. Bloodmeal contents were tested with a direct ELISA assay against nine antisera. Human sleeping quarters (domiciles) and peridomestic dry-shrub fences concentrated most of the T. infestans and T. eratyrusiformis infected with T. cruzi, respectively. The most frequent host-feeding sources of T. infestans were chickens (73.1%) in peridomiciles and humans (73.3%) in domiciles, whereas T. eratyrusiformis fed more often on cavid rodents (92.6%), which thrived in the dry-shrub fences. The main T. cruzi DTU identified in both vectors was T. cruzi I (TcI). Triatoma eratyrusiformis was implicated in the local circulation of TcI among cavies and perhaps mice, but infection with other typically domestic DTUs (TcVI and TcII/TcV/TcVI) indicated overlap between (peri)domestic transmission cycles in both vector species. Because dry-shrub fences were not targeted for routine insecticide spraying, they may act as sources of (peri)domestic reinfestation. Triatoma eratyrusiformis is an emergent secondary vector of T. cruzi and plays a significant role in the local transmission of T. cruzi. PMID- 26849899 TI - Educational class inequalities in the incidence of coronary heart disease in Europe. AB - OBJECTIVE: To estimate the burden of social inequalities in coronary heart disease (CHD) and to identify their major determinants in 15 European populations. METHODS: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) study comprised 49 cohorts of middle-aged European adults free of CHD (110 928 individuals) recruited mostly in the mid-1980s and 1990s, with comparable assessment of baseline risk and follow-up procedures. We derived three educational classes accounting for birth cohorts and used regression-based inequality measures of absolute differences in CHD rates and HRs (ie, Relative Index of Inequality, RII) for the least versus the most educated individuals. RESULTS: N=6522 first CHD events occurred during a median follow-up of 12 years. Educational class inequalities accounted for 343 and 170 additional CHD events per 100 000 person-years in the least educated men and women compared with the most educated, respectively. These figures corresponded to 48% and 71% of the average event rates in each gender group. Inequalities in CHD mortality were mainly driven by incidence in the Nordic countries, Scotland and Lithuania, and by 28-day case-fatality in the remaining central/South European populations. The pooled RIIs were 1.6 (95% CI 1.4 to 1.8) in men and 2.0 (1.7 to 2.4) in women, consistently across population. Risk factors accounted for a third of inequalities in CHD incidence; smoking was the major mediator in men, and High Density-Lipoprotein (HDL) cholesterol in women. CONCLUSIONS: Social inequalities in CHD are still widespread in Europe. Since the major determinants of inequalities followed geographical and gender-specific patterns, European-level interventions should be tailored across different European regions. PMID- 26849901 TI - From the editors. PMID- 26849900 TI - Cardiopulmonary exercise test and sudden cardiac death risk in hypertrophic cardiomyopathy. AB - BACKGROUND: In hypertrophic cardiomyopathy (HCM), most of the factors associated with the risk of sudden cardiac death (SCD) are also involved in the pathophysiology of exercise limitation. The present multicentre study investigated possible ability of cardiopulmonary exercise test in improving contemporary strategies for SCD risk stratification. METHODS: A total of 623 consecutive outpatients with HCM, from five tertiary Italian HCM centres, were recruited and prospectively followed, between September 2007 and April 2015. The study composite end point was SCD, aborted SCD and appropriate implantable cardioverter defibrillator (ICD) interventions. RESULTS: During a median follow up of 3.7 years (25th-75th centile: 2.2-5.1 years), 25 patients reached the end point at 5 years (3 SCD, 4 aborted SCD, 18 appropriate ICD interventions). At multivariate analysis, ventilation versus carbon dioxide relation during exercise (VE/VCO2 slope) remains independently associated to the study end point either when challenged with the 2011 American College of Cardiology Foundation/American Heart Association guidelines-derived score (C index 0.748) or with the 2014 European Society of Cardiology guidelines-derived score (C index 0.750). A VE/VCO2 slope cut-off value of 31 showed the best accuracy in predicting the SCD end point within the entire HCM study cohort (sensitivity 64%, specificity 72%, area under the curve 0.72). CONCLUSIONS: Our data suggest that the VE/VCO2 slope might improve SCD risk stratification, particularly in those HCM categories classified at low-intermediate SCD risk according to contemporary guidelines. There is a need for further larger studies, possibly on independent cohorts, to confirm our preliminary findings. PMID- 26849902 TI - TGF-beta: the connecting link between nephropathy and fibrosis. AB - Renal fibrosis is the usual outcome of an excessive accumulation of extracellular matrix (ECM) that frequently occurs in membranous and diabetic nephropathy. The result of renal fibrosis would be end-stage renal failure, which requires costly dialysis or kidney transplantation. Renal fibrosis typically results from chronic inflammation via production of several molecules, such as growth factors, angiogenic factors, fibrogenic cytokines, and proteinase. All of these factors can stimulate excessive accumulation of ECM components through epithelial to mesenchymal transition (EMT), which results in renal fibrosis. Among these, transforming growth factor-beta (TGF-beta) is proposed to be the major regulator in inducing EMT. Besides ECM protein synthesis, TGF-beta is involved in hypertrophy, proliferation, and apoptosis in renal cells. In particular, TGF-beta is likely to be most potent and ubiquitous profibrotic factor acting through several intracellular signaling pathways including protein kinases and transcription factors. Factors that regulate TGF-beta expression in renal cell include hyperglycemia, angiotensin II, advance glycation end products, complement activation (C5b-9), and oxidative stress. Over the past several years, the common understanding of the pathogenic factors that lead to renal fibrosis in nephropathy has improved considerably. This review will discuss the recent findings on the mechanisms and role of TGF-beta in membranous and diabetic nephropathy. PMID- 26849903 TI - The anti-candidal activity of Satureja khuzistanica ethanol extract against clinical isolates of C. albicans. AB - Candida albicans is the common cause of some infectious diseases such as vaginal candidiasis or candidemia. Due to the emergence of drug resistant isolates of C. albicans, finding a new anti-Candida agent is a new strategy for current treatments. This study evaluated the anti-candidal activity of Satureja khuzistanica ethanol extract against clinical isolates of C. albicans. S. khuzistanica ethanol extract from aerial parts of plant at full flowering stage was evaluated against 30 clinical isolates and two ATCC reference strains of C. albicans by disc diffusion and micro-broth dilution assay. Also, in this study we evaluated the synergistic effects of amphotericin B, clotrimazole and ketoconazole with S. khuzistanica ethanol extract. The means of MIC and MFC of S. khuzistanica ethanol extract against clinical isolates were 299.4 and 722.6 (MUg/mL), respectively. S. khuzistanica ethanol extract increased the anti candidal effect of amphotericin B and ketoconazole, while it had no synergistic effect on clotrimazole against clinical isolates of C. albicans. Therefore, S. khuzistanica ethanol extract can be introduced as a new source of anti-candidal agent against clinical isolates of C. albicans. PMID- 26849904 TI - Tumors of the lacrimal gland. AB - Tumors of the lacrimal gland comprise a wide spectrum, of which the most common demonstrate epithelial and lymphoid differentiation. The diagnosis of lacrimal gland tumors depends primarily on histological evaluation, as do the choice of treatment and prognosis. For some lacrimal gland neoplasms, such as adenoid cystic carcinoma, the outlook is grave. Optimal treatment for several lacrimal gland tumors is also a matter of controversy. However, recent progress has been made in the molecular and genetic understanding of tumorigenesis for such lesions. This article presents an overview of the histopathology of lacrimal gland tumors, together with their epidemiological features, clinical characteristics, and treatment strategies. PMID- 26849905 TI - Globular adiponectin attenuates LPS-induced reactive oxygen species production in HepG2 cells via FoxO3A and HO-1 signaling. AB - AIMS: Adiponectin has been shown to possess potent anti-oxidative properties in various experimental conditions. However, its anti-oxidative effects and underlying mechanisms have not been reported in liver cells. Herein, we investigated the effects of globular adiponectin (gAcrp) on LPS-stimulated reactive oxygen species (ROS) production and its mechanisms underlying in human hepatic cells (HepG2). MAIN METHODS: Intracellular ROS production was determined by fluorescence of 5-chloromethyl-2,7-dichlorodihydrofluorescein diacetate (CM H2DCFDA). NADPH oxidase-dependent ROS formation was determined by lucigenin derived chemiluminescence. Messenger RNA expression level of target genes was determined by quantitative RT-PCR and protein expression was measured by Western blot analysis. KEY FINDINGS: LPS-induced increase in ROS production was prevented by pretreatment with gAcrp in HepG2 cells. Furthermore, gAcrp treatment suppressed LPS-induced activation of NADPH oxidase and increase in mRNA and protein expression of Nox-4. We also found that adiponectin increased expression of FoxO3A and HO-1 and ablation of either of these genes partially restored suppression of LPS-induced ROS production and NADPH oxidase activation by gAcrp, indicating the vital role of FoxO3A and HO-1 signaling in the inhibition of ROS production and NADPH oxidase activation by gAcrp. SIGNIFICANCE: These results suggest that gAcrp prevents LPS-induced ROS production and NADPH oxidase activity in HepG2 cells via FoxO3A and HO-1 signaling-dependent mechanisms. The present study demonstrated a suppressive effect of adiponectin on ROS production in liver cells and presented a novel mechanism underlying suppression of ROS production by adiponectin. PMID- 26849906 TI - The role of mTOR signalling in neurogenesis, insights from tuberous sclerosis complex. AB - Understanding the development and function of the nervous system is one of the foremost aims of current biomedical research. The nervous system is generated during a relatively short period of intense neurogenesis that is orchestrated by a number of key molecular signalling pathways. Even subtle defects in the activity of these molecules can have serious repercussions resulting in neurological, neurodevelopmental and neurocognitive problems including epilepsy, intellectual disability and autism. Tuberous sclerosis complex (TSC) is a monogenic disease characterised by these problems and by the formation of benign tumours in multiple organs, including the brain. TSC is caused by mutations in the TSC1 or TSC2 gene leading to activation of the mechanistic target of rapamycin (mTOR) signalling pathway. A desire to understand the neurological manifestations of TSC has stimulated research into the role of the mTOR pathway in neurogenesis. In this review we describe TSC neurobiology and how the use of animal model systems has provided insights into the roles of mTOR signalling in neuronal differentiation and migration. Recent progress in this field has identified novel mTOR pathway components regulating neuronal differentiation. The roles of mTOR signalling and aberrant neurogenesis in epilepsy are also discussed. Continuing efforts to understand mTOR neurobiology will help to identify new therapeutic targets for TSC and other neurological diseases. PMID- 26849907 TI - Have humans lost control: The elusive X-controlling element. AB - The process of X-chromosome inactivation (XCI) randomly silences one of two X chromosomes in normal female cells. The ability to predict if there is a preference for one of the two Xs to be chosen (and survive) more often as the active X has important repercussions in human health and X-linked disease. Mice have a genetic component that modulates non-random skewing called the X controlling element (Xce). Although the nature of the locus and its mechanisms of action are still under investigation, it is clear that different mouse strains carry unique Xce alleles on their X chromosomes, resulting in distinct skewing phenotypes in the F1 progeny of hybrid crosses. Whether a similar mechanism exists in humans is unclear, and challenges to identifying such a locus include the complexity and diversity of the human genome, the restricted time points and tissue(s) of examination in human subjects, and the lack of a model system recapitulating XCI in early development. In this review we consider the evidence for such a controlling locus in humans, in addition to discussing if we have the power to recognize it given the contribution of selective growth in causing skewed patterns of XCI. PMID- 26849909 TI - Ionizing radiation and heart risks. AB - Cardiovascular disease and cancer are the two leading causes of morbidity and mortality worldwide. As advancements in radiation therapy (RT) have significantly increased the number of cancer survivors, the risk of radiation-induced cardiovascular disease (RICD) in this group is a growing concern. Recent epidemiological data suggest that accidental or occupational exposure to low dose radiation, in addition to therapeutic ionizing radiation, can result in cardiovascular complications. The progression of radiation-induced cardiotoxicity often takes years to manifest but is also multifaceted, as the heart may be affected by a variety of pathologies. The risk of cardiovascular disease development in RT cancer survivors has been known for 40 years and several risk factors have been identified in the last two decades. However, most of the early work focused on clinical symptoms and manifestations, rather than understanding cellular processes regulating homeostatic processes of the cardiovascular system in response to radiation. Recent studies have suggested that a different approach may be needed to refute the risk of cardiovascular disease following radiation exposure. In this review, we will focus on how different radiation types and doses may induce cardiovascular complications, highlighting clinical manifestations and the mechanisms involved in the pathophysiology of radiation induced cardiotoxicity. We will finally discuss how current and future research on heart development and homeostasis can help reduce the incidence of RICD. PMID- 26849908 TI - Repression of harmful meiotic recombination in centromeric regions. AB - During the first division of meiosis, segregation of homologous chromosomes reduces the chromosome number by half. In most species, sister chromatid cohesion and reciprocal recombination (crossing-over) between homologous chromosomes are essential to provide tension to signal proper chromosome segregation during the first meiotic division. Crossovers are not distributed uniformly throughout the genome and are repressed at and near the centromeres. Rare crossovers that occur too near or in the centromere interfere with proper segregation and can give rise to aneuploid progeny, which can be severely defective or inviable. We review here how crossing-over occurs and how it is prevented in and around the centromeres. Molecular mechanisms of centromeric repression are only now being elucidated. However, rapid advances in understanding crossing-over, chromosome structure, and centromere functions promise to explain how potentially deleterious crossovers are avoided in certain chromosomal regions while allowing beneficial crossovers in others. PMID- 26849910 TI - The influence of carotenoid supplementation at different life-stages on the foraging performance of the Southern Corroboree frog (Pseudophryne corroboree): A test of the Silver Spoon and Environmental Matching Hypotheses. AB - Organismal performance can be significantly affected by the nutritional conditions experienced during different life-stages. The Silver Spoon Hypothesis predicts that individuals will always perform better as adults when they experience advantageous conditions during development. In contrast, the Environmental Matching Hypothesis predicts that individuals will perform better if they experience similar conditions during development and adulthood. Past tests of these hypotheses have focussed on the effect of food quantity on growth and development, with little attempt to investigate the effect of individual nutrients on behavioural traits. This study aimed to test the predictions of the Environmental Matching and Silver Spoon Hypotheses by investigating the influence of carotenoid supplementation at different life-stages on the foraging performance of Pseudophryne corroboree. To assess foraging performance, adults were presented with prey in either a cryptic or conspicuous foraging matrix. There was no effect of diet treatment on time to first movement towards prey, number of stalking events, time spent actively foraging, proportion of successful strikes, proportion of prey consumed or number of pedal luring events. These findings indicate that carotenoid supplementation at different life-stages does not influence the foraging performance of P. corroboree, providing no support for either the Silver Spoon or Environmental Matching Hypotheses. PMID- 26849911 TI - Salt-resistant short antimicrobial peptides. AB - Antimicrobial peptides (AMPs) are promising leads for the development of antibiotics against drug resistant bacterial pathogens. However, in vivo applications of AMPs remain obscure due to salt and serum mediated inactivation. The high cost of chemical synthesis of AMPs also impedes potential clinical application. Consequently, short AMPs resistant toward salt and serum inactivation are desirable for the development of peptide antibiotics. In this work, we designed a 12-residue amphipathic helical peptide RR12 (R-R-L-I-R-L-I-L R-L-L-R-amide) and two Trp containing analogs of RR12 namely RR12Wpolar (R-R-L-I W-L-I-L-R-L-L-R-amide), and RR12Whydro (R-R-L-I-R-L-W-L-R-L-L-R-amide). Designed peptides demonstrated potent antibacterial activity; MIC ranging from 2 to 8 MUM, in the presence of sodium chloride (150 mM and 300 mM). Antibacterial activity of these peptides was also detected in the presence of human serum. Designed peptides, in particular RR12 and RR12Whydro, were only poorly hemolytic. As a mode of action; these peptides demonstrated efficient permeabilization of bacterial cell membrane and lysis of cell structure. We further investigated interactions of the designed peptides with lipopolysaccharide (LPS), the major component of the outer membrane permeability barrier of Gram-negative bacteria. Designed peptides adopted helical conformations in complex with LPS. Binding of peptides with LPS has yielded dissociation the aggregated structures of LPS. Collectively, these designed peptides hold ability to be developed for salt resistant antimicrobial compounds. Most importantly, current work provides insights for designing salt-resistant antimicrobial peptides. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 345-356, 2016. PMID- 26849912 TI - Challenge models for atypical Aeromonas salmonicida and Vibrio anguillarum in farmed Ballan wrasse (Labrus bergylta) and preliminary testing of a trial vaccine against atypical Aeromonas salmonicida. PMID- 26849914 TI - Heavy metal pollution and Pb isotopic tracing in the intertidal surface sediments of Quanzhou Bay, southeast coast of China. AB - Concentrations of 16 heavy metals and Pb isotopic ratios in the intertidal surface sediments of Quanzhou Bay were determined to study the pollution level of heavy metals and the sources of Pb. The results showed that most concentrations of Cd, Sn, Mn, Cu, Zn, Cr, Pb, Hg, Ni, Co, Cs, Fe and V were higher than the background values, while most concentrations of Ti, Sb and Sr were lower than the background values. The mean concentrations of Cu, Zn, Pb, Cr and Cd exceeded the first-grade criteria of Chinese marine sediment quality. The geo-accumulation indexes revealed that the sediments had been polluted by some heavy metals. The results of Pb isotopic tracing indicated that the total Pb in the sediments were mainly from parent material, industrial emission and vehicle exhaust with the mean contributions of 38.2%, 51.3% and 10.5%, respectively, calculated by a three end-member model of Pb isotopic ratios. PMID- 26849913 TI - Hydrocarbon pollutants shape bacterial community assembly of harbor sediments. AB - Petroleum pollution results in co-contamination by different classes of molecules, entailing the occurrence of marine sediments difficult to remediate, as in the case of the Ancona harbor (Mediterranean Sea, Italy). Autochthonous bioaugmentation (ABA), by exploiting the indigenous microbes of the environment to be treated, could represent a successful bioremediation strategy. In this perspective we aimed to i) identify the main drivers of the bacterial communities' richness in the sediments, ii) establish enrichment cultures with different hydrocarbon pollutants evaluating their effects on the bacterial communities' composition, and iii) obtain a collection of hydrocarbon degrading bacteria potentially exploitable in ABA. The correlation between the selection of different specialized bacterial populations and the type of pollutants was demonstrated by culture-independent analyses, and by establishing a collection of bacteria with different hydrocarbon degradation traits. Our observations indicate that pollution dictates the diversity of sediment bacterial communities and shapes the ABA potential in harbor sediments. PMID- 26849915 TI - Metal-contaminated resuspended sediment particles are a minor metal-uptake route for the Sydney rock oyster (Saccostrea glomerata)--A mesocosm study, Sydney Harbour estuary, Australia. AB - Resuspension of surficial sediments is considered a key process influencing bioaccumulation of metals in filter-feeders in the contaminated Sydney Harbour estuary (Australia). However, previous investigations were unable to establish a significant relationship between metals in sediments or suspended particulate matter (SPM) and oyster tissue concentrations. This study used a 60-d laboratory mesocosm experiment to expose Sydney rock oysters, Saccostrea glomerata, to a natural range of SPM concentrations with different SPM-metal concentrations. Dissolved metal concentrations were low and the availability of algae provided as food was constant for all treatments. Tissue metal concentrations of Cu, Pb and Zn increased significantly, however, no relationship was determined between tissue metal concentrations in the oyster and either SPM or SPM-metal concentrations. The results indicated that exposure to resuspended contaminated sediment particles contributed little to the observed metal uptake. Dissolved or algae food sources appear to be more important for metal accumulation in these oysters. PMID- 26849916 TI - Excitation-emission matrix scan analysis of raw fish oil from coastal New Jersey menhaden collected before and after Hurricane Sandy. AB - The impact of Hurricane Sandy (October 29, 2012) on PAH exposure was investigated in adult Atlantic menhaden (Brevoortia tyrannus) collected along the NJ coast. Collections were made in August, September and/or October of 2011, 2012 and 2013. PAHs were monitored in raw fish oil using excitation-emission matrix (EEM) spectroscopy. Results showed that raw fish oils had relatively high levels of high molecular weight, PAH-like compounds (173 to 24,421ng/mL) compared to values reported for bile in other species. EEM profiles resembled that of crude oil and excluded matrix interference by some common biological molecules that also fluoresce. Concentrations and EEM profiles varied by collection; however, collection ship, month, year and fish size did not account for the data. Replicates showed that fish from the same catch had similar PAH exposure. Overall, Hurricane Sandy did not alter body burdens of PAHs in raw fish oil of menhaden. PMID- 26849917 TI - Potential of the isolated lung technique for the examination of sildenafil absorption from lung-delivered poly(lactide-co-glycolide) microparticles. AB - Herein, we challenged the isolated lung (IL) technique to discriminate the performance of lung-delivered polymeric microparticles (MPs) having distinct drug release rates. For this purpose, sildenafil-loaded poly(lactide-co-glycolide) MPs were administered to the airspace of an IL model and the drug absorption profile was monitored. MPs (particle size of ~5MUm) composed of PLGA of lower molecular weight (and glass transition temperature) manifested in the most rapid in vitro drug release (half-times ranging from <15 to ~200min). Moreover, microencapsulation resulted in a delayed sildenafil transfer over the air/perfusate barrier (half-times ranging from <5 to ~230min), where the actual ex vivo absorption profile depended on the release behavior of the utilized formulation. Finally, the obtained in vitro and ex vivo results were tested for level C, B and A correlations. The plotted data showed good agreement (R(2)>0.96) and the slopes of the resulting lines of regression (i.e., 0.80-0.85) indicated a slightly elevated in vitro drug release behavior. Overall, the IL model was able to differentiate between distinct microparticulate formulations and is, therefore, a valuable technique for early testing of potential inhalable controlled release medications. PMID- 26849918 TI - Emerging landscape of cell penetrating peptide in reprogramming and gene editing. AB - The plasma membrane remains a major barrier for intracellular drug delivery, to overcome this issue, a variety of approaches have been developed and used to deliver therapeutic cargos. Among these approaches, cell penetrating peptide (CPP) is promising and affords widely used vector for efficient intracellular delivery of cargos. Moreover, the latter findings including iPS reprogramming and direct transdifferentiation as well as gene editing have gradually become hot research topic; because their application in tissue engineering and disease modeling have great potential to advance innovation in precision medicine. Since the beginning, research on these approaches is mainly based on virus transduction system, while, under the consideration for obviating the risk of mutagenic insertion and enables more accurate controlling, CPP-based efficient virus-free delivery strategy has been used recently. In this review, we summarize the existing CPP-based delivery system, emerging landscape of CPP application in stem cell manipulation and reprogramming, along with CPP contributions to gene editing techniques. PMID- 26849919 TI - Development and in vivo evaluation of child-friendly lopinavir/ritonavir pediatric granules utilizing novel in situ self-assembly nanoparticles. AB - The aim of this study was to develop a nanotechnology to formulate a fixed-dose combination of poorly water-soluble drugs in a children-friendly, flexible solid dosage form. For diseases like HIV, pediatric patients are taking multiple drugs for effective treatments. Fixed-dose combinations could reduce pill burdens and costs as well as improving patient adherence. However, development of fixed-dose combinations of poorly water-soluble drugs for pediatric formulations is very challenging. We discovered a novel nanotechnology that produced in situ self assembly nanoparticles (ISNPs) when the ISNP granules were introduced to water. In this study, antiretroviral drug granules, including lopinavir (LPV) ISNP granules and a fixed-dose combination of LPV/ritonavir (RTV) ISNP granules, were prepared using the ISNP nanotechnology, which spontaneously produced drug-loaded ISNPs in contact with water. Drug-loaded ISNPs had particle size less than 158nm with mono-dispersed distribution, over 95% entrapment efficiency for both LPV and RTV and stability over 8h in simulated physiological conditions. Drug-loaded ISNP granules with about 16% of LPV and 4% of RTV were palatable and stable at room temperature over 6months. Furthermore, LPV/RTV ISNP granules displayed a 2.56 fold increase in bioavailability and significantly increased LPV concentrations in tested tissues, especially in HIV sanctuary sites, as compared to the commercial LPV/RTV tablet (Kaletra(r)) in rats. Overall, the results demonstrated that the novel ISNP nanotechnology is a promising platform to manufacture palatable, "heat" stable, and flexible pediatric granules for fixed-dose combinations that can be used as sachets and sprinkles. To the best of our knowledge, this is the first report on this kind of novel nanotechnology for pediatric fixed-dose combinations of poorly water-soluble drugs. PMID- 26849920 TI - Editorial Comment. PMID- 26849921 TI - Author Reply. PMID- 26849922 TI - Exploring the fungal protein cadre in the biosynthesis of PbSe quantum dots. AB - While a large number of microbial sources have recently emerged as potent sources for biosynthesis of chalcogenide quantum dots (QDs), studies regarding their biomimetic strategies that initiate QD biosynthesis are scarce. The present study describes several mechanistic aspects of PbSe QD biosynthesis using marine Aspergillus terreus. Scanning electron microscopic (SEM) studies indicated distinctive morphological features such as abrasion and agglomeration on the fungal biomass after the biosynthesis reaction. Further, the biomass subsequent to the heavy metal/metalloid precursor was characterized with spectral signatures typical to primary and secondary stress factors such as thiol compounds and oxalic acid using Fourier Transform Infra-Red Spectroscopic (FTIR) analysis. An increase in the total protein content in the reaction mixture after biosynthesis was another noteworthy observation. Further, metal-phytochelatins were identified as the prominent metal-ion trafficking components in the reaction mixture using Liquid Chromatography Mass Spectroscopic analysis (LCMS). Subsequent assays confirmed the involvement of metal binding peptides namely metallothioneins and other anti-oxidant enzymes that might have played a prominent role in the microbial metal detoxification system for the biosynthesis of PbSe QDs. Based on these findings a possible mechanism for the biosynthesis of PbSe QDs by marine A. terreus has been elucidated. PMID- 26849923 TI - [Randomized control multi-center clinical study of mycophenolate mofetil and cyclophosphamide in the treatment of connective tissue disease related interstitial lung disease]. AB - OBJECTIVE: To investigate the efficacy and safety of mycophenolate mofetil (MMF) in the treatment of connective tissue disease-related interstitial lung disease (CTD-ILD). METHODS: A total of 60 patients with CTD-ILD, confirmed by high resolution computer tomography (HRCT), were enrolled from five clinical centers from July 2010 to July 2014. In addition to the basic glucocorticoid treatment, patients received intravenous cyclophosphamide (Group A) or oral MMF (Group B) for one year. Pulmonary function was assessed at the 3, 6, 12 months. All adverse events were recorded and efficacy and safety were evaluated at the end of this trial. RESULTS: Total 60 patients were enrolled, each group had 30 patients. 5 patients withdrew voluntarily from each group, 2 and 3 patients died in group A and B, respectively. Total 45 patients completed this trial. Neither lung function, HRCT nor adverse events had differences between the two groups or within group (P>0.05). When the analysis was done among patients with forced vital capacity (FVC) <= 75% and forced expiratory volume in one second (FEV1)% <= 75%, there were significantly statistical differences in FVC and FEV1 at 6th month compared with prior treatment in group A (both P<0.05). And there were significant increase in FVC and FEV1 at 12 months in group B (both P<0.05). But there was no statistical difference between the two groups. For the patients with diffusion capacity for carbon monoxide (DLco) <= 65%, there were significant increase in group A at 3, 6 and 12 months (P<0.01, P<0.05, P<0.05, respectively). but no significant increase was found in patients on MMF. And there was no difference between the two groups. No statistical difference existed in survival rate between these two groups (P>0.05). CONCLUSIONS: MMF has comparative effect as cyclophosphamide in the remission or stability of lung function and HRCT manifestations of CTD-ILD patients. MMF is generally well-tolerated, but its efficacy in maintenance therapy and long-term safety remains to be clarified. PMID- 26849924 TI - [Clinical applications of apparent diffusion coefficient value for evaluation of hip joint of ankylosing spondylitis active lesions]. AB - OBJECTIVE: To evaluate the apparent diffusion coefficient (ADC) value in differential diagnosis of ankylosing spondylitis active lesions. METHOD: A total of 68 patients with AS involving hip joint who were diagnosed in Third Affiliated Hospital of Southern Medical University form March 2010 to December 2014 were evaluated by MRI. The ADC values of the hip joint lesions were measured and compared in 38 cases of ankylosing spondylitis active lesions (active group) and 30 cases of ankylosing spondylitis in stable period (stable group), all cases were confirmed by clinical diagnosis. RESULTS: There are 238 lesions were detected demonstrating hyperintens in DWI and ADC picture. The mean ADC values of active group and stable group were (1.00 +/- 0.13) * 10-3 mm2/s and (0.65 +/- 0.12) * 10-3 mm2/s (t=-11.85, P=0.00). The correlation coefficient between ADC and BASDAI score is 0.831 (P<0.01). ROC curve showed that the threshold ADC value differentiating active group and stable group was 0.81 * 10-3 mm2/s, with a sensitivity of 94.7%and specificity of 90%. CONCLUSION: The ADC value of hip joint lesion of AS patient can help to determine the nature of the ankylosing spondylitis. PMID- 26849925 TI - [Association of diffusion tensor imaging abnormalities with executive dysfunction in patients with leukoaraiosis]. AB - OBJECTIVE: To explore abnormal microstructural changes of white matter using diffusion tensor imaging (DTI) in patients with leukoaraiosis (LA), and to determine the association of such abnormalities of DTI parameters with cognitive function, especially executive function. METHODS: A total of 44 patients with LA and 36 healthy controls were recruited from the department of Neurology, Beijing Chaoyang Hospital, Capital Medical University between July 2010 and June 2011. The two groups were matched for age, sex, education, and vascular risk factors. All the subjects underwent the scans of conventional magnetic resonance imaging (MRI), DTI and neuropsychological assessment. The values of mean diffusivity (MD) and fractional anisotropy (FA) were measured within white matter lesions (WML) and normal appearing white matter (NAWM). Three regions of interest (ROIs) were located in the white matter of centrum semiovale, anterior periventricular white matter and posterior periventricular white matter. The relationships between the cognitive function and the abnormalities of DTI parameters were analyzed. RESULTS: (1) Patients with LA performed significantly worse cognitive function, especially in the fields of executive function. The results of our study showed that patients with LA were associated with comprehensive cognitive function deficits, including mini mental state examination (MMSE) (24.4 +/- 3.2 vs 28.3 +/ 1.2), montreal cognitive assessment (MoCA) (21.2 +/- 3.4 vs 25.7 +/- 1.7), Stroop B (69.2 +/- 13.5 vs 43.3 +/- 5.0), Stroop C (141.2 +/- 42.6 vs 64. 8 +/- 10.0), Stroop (C-B) (72.0 +/- 41.9 vs 21.5 +/- 9.4), trail making test (TMT)-A (73.4 +/- 15.4 vs 31.1 +/- 7.1), TMT-B (126.2 +/- 17.5 vs 81.4 +/- 5.7), digit symbol test (25.2 +/- 5 .4 vs 36.7 +/- 5.1) (all P<0.05). (2) The values of FA were lower, and MD were higher in WML than NAWM and controls in all the three ROIs (P<0.05). The values of FA in NAWM located in centrum semiovale and posterior periventricular white matter were lower than controls (P<0.05). The values of MD in NAWM located in anterior periventricular white matter were higher than controls (P<0.05). (3) The values of FA of NAWM located in anterior periventricular correlated inversely with the Z scores of executive function (r= 0.311, P=0.04). CONCLUSIONS: Patients with LA are related with significant cognitive impairment, especially in the domains of executive dysfunction. Microstructural integrity of both white matter lesions and NAWM is associated with executive function. The underlying executive dysfunction in LA may attribute to the damage of the prefrontal-subcortical circle. PMID- 26849926 TI - [Values of different diagnosis criteria for predicting the prognosis of amyotrophic lateral sclerosis]. AB - OBJECTIVE: To evaluate the value of different diagnosis criteria for predicting the prognosis of amyotrophic lateral sclerosis (ALS). METHODS: Between January 2011 and December 2012, all patients with a diagnosis of ALS referred to and assessed at Peking University Third Hospital (PUTH) were screened. Baseline demographic details and clinical data were collected from the patient's first visit to PUTH. According to the Airlie House and Awaji-shima criteria, the levels of diagnostic certainty were categorized. The follow-up period was 24 months. Receiver operating characteristic (ROC) curves were made to compare the efficiency of the two ALS-criteria. RESULTS: According to the Airlie House and Awaji-shima criteria, there was no difference in the outcome event rate among the different levels of diagnostic certainty (P>0.05). Among the sub-group with diagnostic delay time <12 months, the outcome event rate of high diagnostic level patients was higher than that of low diagnostic level patients (chi2 =43.283, P<0.05). For the non-bulbar onset patients whose diagnostic delay time was under 12 months, the areas under the ROC curves of the Airlie House to predict the prognosis of ALS was 0.603, which was significantly higher than the baseline area of 0.500 (P<0.05). CONCLUSION: The Airlie House criteria can predict the prognosis of non-bulbar onset ALS whose diagnostic delay time were under 12 months. PMID- 26849927 TI - [Value of MRI in preoperative evaluation of carotid body tumor]. AB - OBJECTIVE: To evaluate the value of MRI in preoperative evaluation of carotid body tumor. METHODS: A retrospective study was including 32 CBT of 28 patients of carotid body tumor with complete clinical, imaging and pathological data in our hospital. The MRI images of vascular adjacent length, no enhancement vascular wall, carotid displacement, wrapping angle and carotid stenosis were analyzed respectively in tumor resection group, tumor dissection and artery repair group, and tumor and artery resection group. The results were compared with surgery. RESULTS: The indexes of vascular adjacent average length were (3.2 +/- 0.8), (3.4 +/- 0.7) and (3.8 +/- 1.0) cm, respectively.The indexes of vascular adjacent average length and vascular displacement, which all showed no significant difference between each operation group (P=0.577, 0.859). The indexes of no enhancement vascular wall, wrapping angle and carotid stenosis, which all showed significant difference between each operation group (all P<0.01). Compared with the surgical and pathological findings, with no enhancement vascular wall <2/3 circumference as the index of carotid artery repair or resection, the sensitivity, specificity and accuracy were 86.4%, 90%, 87.5% respectively. With wrapping angle >1/3 circumference as the index of carotid artery repair or resection, the sensitivity, specificity and accuracy were 86.4%, 90%, 87.5% respectively. With carotid stenosis as the index of carotid artery resection, the sensitivity, specificity and accuracy were 80%, 100%, 93.7% respectively. CONCLUSION: The no enhancement vascular wall, wrapping angle and carotid stenosis have a correlation with carotid artery intervention.The no enhancement vascular wall <2/3 circumference, wrapping angle >1/3 circumference and carotid stenosis have a certain value in preoperative evaluation of carotid body tumor, although vascular adjacent average length and vascular displacement have limited value. PMID- 26849928 TI - [Comparison on efficacy between the different timings of methotrexate administration combined with laproscopy in the treatment of salpingocyesis]. AB - OBJECTIVES: To compare pretreatment and intra-operative methotrexate (MTX) administration when combined with laproscopy in the treatment of salpingocyesis. METHODS: All 200 patients with salpingocyesis treated with laproscopy in Jiangwan Hospital from Jan, 2010 to Dec, 2014 were enrolled and divided into group A and B, 100 patients in each. In group A, the patients were administered with MTX 50 mg/kg by intramuscular injection 24-48 h before the surgery. In group B, the patients were administered with MTX 20 mg in 2 ml normal saline to the target tubal seromuscular layer after the ectopic pregnancies were removed. Then, the following characteristics would be compared between the groups including the medical condition during the operation, post-operative body temperature, serum beta-human chorionic gonadotropin (beta-HCG) reduction, the rate of refractory ectopic pregnancy and tubal patency. RESULTS: The bleeding volume during the surgery (P<0.01) was significantly reduced and the operation duration (P<0.05) was significantly shortened in group A. The serum beta-HCG level (P<0.05) was also significantly reduced 4 and 7 days after the surgery in group A. There was significantly difference on the rate of tubal patency (P<0.01) between the groups. There was no refractory ectopic pregnancy in either groups after the surgery. And there were no significant differences on the post-operative temperature, period of serum beta-HCG moving to the normal level between the groups (P>0.05). CONCLUSIONS: Both pretreatment and intra-operative MTX administration showed good efficacy. But the surgery duration shortening, bleeding decreasing during the operation and tubes retaining were seen in group A. For this reason, we believe pro-operative MTX administration would be better for the patients with childbearing requests. PMID- 26849929 TI - [Vertebroplasty compared with conservative method of integrated Chinese and Western Medicine in patients with osteoporotic vertebral compression fractures]. AB - OBJECTIVE: To compare the effects of percutaneous vertebroplasty (PVP) versus conservative method of integrated Chinese and Western Medicine for pain relief and functional outcome in patients with painful osteoporotic vertebral fractures. New fractures and secondary adverse effects were also analyzed during a mid-long term follow-up period. METHODS: Patients were recruited to this prospective nonrandomized trial from a single hospital. Patients were aged 55 years or older, had vertebral compression fractures on spine radiograph (level of fracture at T6 or lower; bone oedema on MRI), with back pain for 6 weeks or less, and a visual analogue scale (VAS) score of 6 or more. Patients were nonrandomly assigned to PVP group or conservative treatment group according to their own desire. After 2 weeks, patients from the conservative group could change therapy to PVP. VAS for pain and Oswestry disability index (ODI) questionnaire scores were assessed before and 1 week, 1 month, 3, 6, 12, 24, 36, 48, and 60 months after the treatment. Other data included patients' baseline characteristics before the treatment, new fractures and secondary adverse effects were also recorded. RESULTS: A total of 181 consecutive patients were nonrandomly allocated to receive PVP (n=103) or conservative treatment (n=78) between December 2009 and August 2013. Six patients transferred to PVP group after 2 weeks conservative therapy. Pain relief and functional outcomes were significantly better in PVP group than in conservative group, as determined by VAS scores (3.67-1.13 vs 7.38 2.39) and ODI scores (23.55-5.83 vs 36.10-13.88) at 1 week, 1 month, 3 and 6 months (all P< 0.01). Both VAS and ODI scores decreased in PVP group showed no statistical significance at 1 year when compared with conservative group (P>0.05). However, pain relief and functional outcomes were significantly better at most of the subsequent follow-up points. The patients with complete pain relief (VAS<1) were significantly better in PVP group than in conservative group (P< 0.01) at all of the follow-up points. There were 17 patients died (PVP group: n=8) and 31 cases occurred secondary vertebral fractures (PVP group: n=19) during the follow-up periods. No serious complications or adverse events were related to PVP technique. CONCLUSION: PVP has immediate pain relief and functional improvement compared with conservative treatment. PVP should be considered as the treatment of first choice for symptomatic osteoporotic vertebral fractures. However, for patients with VAS < 5, conservative method of integrated Chinese and Western Medicine may perform well. PMID- 26849931 TI - [To cure coronoid process fractures of ulna through anterior approach of the elbow and frame shape plate internal fixation]. AB - OBJECTIVE: To observe the effect of open reduction through anterior approach of the elbow and frame shape plate internal fixation in the treatment of coronoid process fracture of ulna. METHODS: From August 2011 to October 2014, 17 patients with coronoid process fracture of ulna were treated with open reduction through anterior approach of the elbow and internal fixation with frame shape plate. There were 12 males and 5 females with an average age of 36.4 years old. A "S" shape anterior incision of the elbow was used to expose the fracture. The soft tissue of the bone block was kept intact and the fracture was fixed with internal frame shape plate. The therapeutic effects were evaluated by hospital for special surgery (HSS) elbow score system. RESULTS: All the patients were followed up for 8-26 months (average 14 months). The fractures clinically healed at an average time of 10 weeks (ranged from 9 to 11 weeks). There was no myositis ossificans happened. The patients' elbow joint function according to the HSS scores were 12 cases excellent (70.6%), good 4(23.5%) and moderate 1 (5.9%). The total excellent and good rate was 94.1%. CONCLUSION: Open reduction through anterior approach of the elbow and internal fixation with frame shape plate is effective to reach anatomical reduction in the treatment of the coronoid process fracture of ulna, with little damage and strong fixation. PMID- 26849930 TI - [Comparative evaluation of the techniques and effects of RetroButton and Interference Screw in anterior cruciate ligament reconstruction]. AB - OBJECTIVE: To evaluate the difference between RetroButton and Interference Screw in Anterior Cruciate Ligament (ACL) Reconstruction. METHODS: Ninety-seven patients with ACL rupture were treated by arthroscopic reconstruction with RetroButton and Interference Screw from June 2008 to December 2011. There were 54 males and 43 females with an average age of 27.5 years (range, 18-53 years). The preoperative magnetic resonance imaging (MRI) of all injured knees revealed the rupture of ACL. The average time from injury to surgery was 13.1 days (range, 6 20 days). All the patients were randomly divided into RetroButton group and Interference Screw group. And all the operations were performed under arthroscopy. Patients were instructed to walk with crutches and weight-bearing 4 weeks after operation. Walk without crutches was allowed 6 to 8 weeks after reconstruction and normal daily activities were gradually resumed. RESULTS: The average follow-up was 54.6 months (range 48-60 months). No adverse biological reactions or infection ever occurred. There was no spontaneous rupture or laxity of graft. The average Lysholm knee score[(56.1 +/- 7.9) vs (93.1 +/- 6.1); (55.3 +/- 8.5) vs (93.2 +/- 5.7)], KT-1000 examination [(9.2 +/- 1.8) vs (2.1 +/- 1.4); (9.5 +/- 1.7) vs (2.1 +/- 1.5)], International Knee Documentation Committee (IKDC) subjective and objective score [(49.7 +/- 5.9) vs (91.7 +/- 5.0); (50.2 +/ 6.3) vs (91.0 +/- 6.1)] were improved significantly in both two groups (all P<0.01), and there was no significant difference between the two groups [(93.1 +/ 6.1) vs (93.2 +/- 5.7), P>0.05]. CONCLUSIONS: ACL reconstruction using RetroButton and Interference Screw are simple and effective, and can lead to good ligamentous stability and knee function. The two kinds of fixation methods have no significant difference in short and medium term effect. Long-term follow-up should be performed to confirm the durable stability of the knee. PMID- 26849932 TI - [Effects of posterior lumbar spinal fusion on the stability of unstable lumbar segment and biomechanical properties of adjacent segments: a finite element study]. AB - OBJECTIVE: To explore the effects of posterolateral lumbar fusion (PLF) and posterior lumbar interbody fusion (PLIF) on the stability of postoperative unstable single lumbar segment and the biomechanical alterations of the adjacent segments. METHODS: A finite element model of L3-S1 segments with a single segmental degeneration at the L4-5 level was established, and the model of L4-5 segmental instability after posterior laminectomy and facetectomy was also established, in which laminar and interior 2/3 area of bilateral facet joints were resected. Physical loads were applied to the models and the changes of the range of motion (ROM) at L4-5 level in different models were recorded at the condition of flexion, extension, lateral bending and rotation. PLF and PLIF were performed on postoperative unstable model respectively, the changes of the ROM at L4-5 level, the ROM and the stress on the adjacent discs in different models were recorded. RESULTS: Compared to the unstable model, the L4-5 segmental stability was restored after PLF or PLIF. The ROMs of L3-4 and L5-S1 levels were similar to the preoperative unstable model. The stress on adjacent discs (L3-4 and L5-S1) was increased significantly, and maximum stress distribution changed and concentrated in the anterior annulus fiber in the two fusion models. There was no significant difference of the maximum stress on adjacent discs between PLF and PLIF models [(1.056 +/- 0.061) mPa vs (1.070 +/- 0.075) mPa; (1.147 +/- 0.055) mPa vs (1.162 +/- 0.075)mPa, P>0.05]. CONCLUSIONS: Lumbar segmental stability after posterior laminectomy and facetectomy can be recovered by both PLF and PLIF. Both PLF and PLIF may increase the possibility of adjacent segment degeneration because of the augmentation of maximum stress on adjacent discs. PMID- 26849933 TI - [Diagnosis and treatment of congenital diaphragmatic hernia during perinatal period]. AB - OBJECTIVE: To explore prenatal diagnosis, methods of clinical evaluation, therapy and prognosis for fetal congenital diaphragmatic hernia to guide clinical practice. METHODS: Analysis was done on data from all 26 patients who were diagnosed with fetal congenital diaphragmatic hernia by ultrasonography and delivered at Beijing obstetrics and gynecology hospital, capital medical university from Jan 1st, 2009 to Mar 31st, 2015. RESULTS: Out of the 26 patients, fetal congenital diaphragmatic hernia occurred at left side thoracic cavity in 25 patients, only one fetal congenital diaphragmatic hernia occurred at right side thoracic cavity. There were 14 patients who abandoned fetuses and induced labour in second trimester, and there were 12 patients who delivered in lategestation. 6 neonates received surgical procedures and survived. CONCLUSIONS: Prenatal ultrasonography is an important method to diagnose fetal congenital diaphragmatichernia.Comprehensive evaluation of the prognosis should be done based on site of diaphragmatic hernia, whether or not complicating with other abnormalities, pulmonary development condition.Intrauterine therapy can be applied during pregnancy, and surgical procedures can be conducted at fitting time after birth. PMID- 26849934 TI - [Brown tumor: clinical, pathological and imaging manifestations]. AB - OBJECTIVE: To explore the clinical, pathological characteristics and imaging manifestations of brown tumors caused by hyperparathyroidism, to improve the cognition of the disease. METHODS: The clinical, pathological characteristics and imaging manifestations of 15 cases of pathologically confirmed brown tumors were retrospectively reviewed. To analyze the imaging and pathological correlations, in addition, between the primary and secondary hyperparathyroidism led to brown tumors differential diagnoses. Rseults: In the 15 cases, aged from 26 to 66 years with median age of 51 years, 7 cases were caused by primary hyperparathyroidism, 8 cases secondary to long-term hemodialysis. Of the 15 cases(total of 34 lesions), 11 cases were multi-part bone involved. 13 of 15 patients for osteoporosis and 2 cases were osteosclerosis.32 lesions had bone destruction, 26 lesions showed expansive bone destruction, 6 showed soluble bone destruction, 12 lesions had harden edge. 23 lesions in bone destruction had calcification or ossification internal. 13 cases with soft tissue mass, enhanced significantly can be found in 3 cases. 2 lesions occured in the skull, bone density increased and the plate edge blur. pathological findings fibrous tissue , rich in blood vessels, scattered hemosiderin deposition, osteoid tissue around it. CONCLUSION: Brown tumor has relatively specific clinical history and laboratory characteristics. The imaging features include harden edge, in bone destruction has calcification or ossification internal and with soft tissue mass some enhanced significantly. The secondary brown tumor more multi-part destruction and more vertebra were involved than the primary.We can find osteosclerosis in secondary brown tumor. Those characteristic features were important to help for the diagnosis of the brown tumor. PMID- 26849935 TI - [Antagonistic effect and mechanism of Rosuvastatin on myocardial apoptosis in rats with acute myocardial infarction]. AB - OBJECTIVE: To investigate the protective effect of Rosuvastatin on myocardial cells in rats with acute myocardial infarction and its possible mechanism. METHODS: Rats were randomly assigned to four groups: Control group, Sham group, AMI and Rosuvastatin group. The levels of lactate dehydrogenase (LDH) and creatine jubase (CK), the vitality of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were detected by assay kits and the levels of C-reactive protein (CRP), tumor necrosis factor (TNF) alpha and interleukin (IL)-6 expression were detected by enzyme linked immunosorbent assay (ELISA). TTC/Evans blue staining was used to determine the relative myocardial infarction area, HE staining was used to detect pathologic changes and myocardial apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL). What's more, Western blot was used to detect the protein expression of B cell lymphoma-2 (Bcl-2), Bax, cleaved-Caspase-3, Rock1, Rock2, I-kappaB and NF kappaBp65. RESULTS: The model of acute myocardial infarction rats was established. Compared with Sham group, the myocardial pathological changes were more severe, and the apoptosis number, the production of inflammatory factors and oxidative damage were significantly increased in AMI group. Compared with AMI group, the relative area of infarction myocardium (43% +/- 4% vs 31% +/- 8%, P=0.004 3) was dramatically reduced, the levels of LDH (2 545.45 +/- 613.67 U/L vs 1 573.43 +/- 373.72 U/L, P=0.02) and CK (7.49 +/- 1.75 U/ml vs 4.42 +/- 1.28 U/ml, P=0.04) in serum were significantly lower (P<0.01), the myocardial pathological damage degree was relieved, the apoptosis number (41% +/- 8% vs 23% +/- 6%, P=0.014 7) was significantly decreased, the expression of Bax (1.17 +/- 0.10 vs 0.57 +/- 0.08, P=0.003) and cleaved-Caspase-3 (1.31 +/- 0.07 vs 0.70 +/- 0.01, P=0.004) were dramatically reduced, and the expression of Bcl-2 (0.19 +/- 0.01 vs 0.32 +/- 0.01, P=0.003) was enhanced in Rosuvastatin group. Furthermore, the production of inflammatory factors and oxidative damage were effectively alleviated (P<0.05), the protein expression of Rock1, Rock2 and NF-kappaBp65 were declined in Rosuvastatin group (P<0.01). CONCLUSION: Rosuvastatin can effectively alleviate the cardiomyocyte apoptosis induced by acute ischemia, and its main mechanism may be the inhibition on RhoA/ROCK activation and the oxidative stress and inflammation reaction mediated by it. PMID- 26849936 TI - [Effect of icariin on hypoxia/reoxygenation injury in neonatal rat cardiomyocytes]. AB - OBJECTIVE: To investigate the effect of icariin on myocardial hypoxia reoxygenation injury and the possible mechanism. METHODS: Neonatal Sprague-Dawley rat cardiomyocytes in primary culture were treated with different concentrations of icariin for 24 h prior to hypoxia/reoxygenation injury. Cardiomyocyte apoptosis was evaluated with Tunel staining. The expression levels of apoptosis proteins were detected by Western blotting. The nuclear translocation of p65 was evaluated by immunofluorescence. The p65 signaling pathway was also detected by Western blotting. RESULTS: Myocardial apoptosis rate significantly increased after hypoxia/reoxygenation (control: 1.5% +/- 0.1%; MODEL: 23.4% +/- 1.3%, P<0.05). While icariin significantly reduced cardiomyocyte apoptosis induced by hypoxia/reoxygenation (1 umol/L icariin: 7.2% +/- 0.9%; 10 umol/L icariin: 3.9% +/- 0.8%, both P<0.05). Western blot showed that the expression levels of pro apoptotic protein, Bax, increased significantly (control: 0.19 +/- 0.05; MODEL: 0.41 +/- 0.03, P<0.05), while the expression of anti-apoptotic protein, B-Cell CLL/Lymphoma 2 (BCL-2), was significantly reduced (control: 0.15 +/- 0.02; MODEL: 0.03 +/- 0.01, P<0.05) after hypoxia/reoxygenation. Notably, icariin reduced the expression of Bax (1 umol/L icariin: 0.29 +/- 0.01; 10 umol/L icariin: 0.33 +/- 0.03, both P<0.05) and increased expression of BCL-2 (1 umol/L icariin: 0.10 +/- 0.03; 10 umol/L icariin: 0.11 +/- 0.02, both P<0.05). Immunofluorescence showed that NFkappaB-p65 nuclear translocation in cardiomyocytes was increased after hypoxia/reoxygenation (control: 3.6% +/- 0.5%; MODEL: 89.5% +/- 4.8%, P<0.05), while icariin reduced the nuclear translocation of p65 (1 umol/L icariin: 32.6% +/- 2.3%; 10 umol/L icariin: 10.6% +/- 1.0%, both P<0.05). Moreover, icariin reduced the activation of p65 and phosphorylation of IKBalpha induced by hypoxia/reoxygenation in cardiomyocytes. CONCLUSION: Icariin can protect cardiomyocytes against hypoxia reoxygenation injury, which may be via blocking p65 signaling pathway. PMID- 26849937 TI - Neuroprotective effect of berberine is mediated by MAPK signaling pathway in experimental diabetic neuropathy in rats. AB - The mechanisms leading to diabetic neuropathy are complex. As an active component in several traditional Chinese medicines, berberine has a beneficial effect in the treatment of diabetes with hyperlipidemia. This study evaluated the protective effects of berberine on diabetic neuropathy induced by streptozotocin and a high-carbohydrate/high-fat diet in rats. Diabetic neuropathy was induced in rats by intraperitoneal injection of 35 mg/kg streptozotocin and a high carbohydrate/high-fat diet. Two weeks after diabetes induction, rats were treated with berberine (100 mg/kg) and rosiglitazone (4 mg/kg) for 24 weeks. Rats were studied using evoked potentials, the Morris water maze, transmission electron microscopy, real-time PCR, and Western blotting. Blood glucose, glycated hemoglobin, lipid profile, body weight, evoked potentials, and memory were altered in diabetic rats, as was the hippocampal expression of neuritin mRNA, p38 mitogen-activated protein kinase mRNA, c-Jun N-terminal kinase (JNK) mRNA, extracellular signal-regulated kinase mRNA and the phospho-proteins of p38, JNK, and extracellular signal-regulated kinase. In diabetic rats, berberine decreased body weight and the blood levels of glucose, glycated hemoglobin, triglyceride, and total cholesterol, improved memory and affected evoked potential by decreasing latency. Berberine decreased the mRNA expression of neuritin, p38, and JNK and the protein expression of neuritin, p-p38, and p-JNK. Slight micropathological changes were observed in the hippocampus of berberine-treated diabetic rats. These findings suggest that berberine has a beneficial effect against diabetic neuropathy by improving micropathology and increasing neuritin expression via the mitogen-activated protein kinase signaling pathway. PMID- 26849938 TI - Neurobehavioral effects of liraglutide and sitagliptin in experimental models. AB - Glucagon-like peptide (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP 4) inhibitors are two currently approved therapies for type 2 diabetes mellitus (T2DM). Present study evaluated the effect of liraglutide (a long-acting GLP-1 agonist) and sitagliptin (a DPP-4 inhibitor) on nociception, anxiety, depression like behavior and cognition in rats or mice. Nociception was assessed using tail flick test; anxiety-behavior in open-field test and elevated plus maze (EPM) test while depression-like behavior was evaluated in forced swim test (FST) and tail suspension test (TST). Cognition was assessed in EPM and Morris water maze (MWM) following memory deficit induced by pentylenetetrazole (PTZ) or scopolamine. In tail-flick test sitagliptin (6 mg/kg) produced transient nociceptive effect. Liraglutide (200 ug/kg) reduced peripheral square crossings by rats in open field test as well as reduced closed arm entries in the EPM, indicating a decline in exploratory behavior. In FST and TST models for depression, the duration of immobility with sitagliptin (6 mg/kg) was reduced significantly in comparison to control group suggesting its antidepressant effect. Liraglutide did not show any antidepressant action. In EPM test for cognition, liraglutide and sitagliptin ameliorated the increase in transfer latency caused by PTZ in a dose-dependent manner. In MWM liraglutide and sitagliptin prevented the scopolamine-induced increase of the escape latency. This study shows that sitagliptin has mild antinociceptive effect and anti-depressant effect in the animal models of depression while liraglutide did not have such an effect. Liraglutide showed anxiogenic effects in the animal models. Both liraglutide and sitagliptin produced cognitive improvement in the animal models. PMID- 26849939 TI - Inhibition of human alpha7 nicotinic acetylcholine receptors by cyclic monoterpene carveol. AB - Cyclic monoterpenes are a group of phytochemicals with antinociceptive, local anesthetic, and anti-inflammatory actions. Effects of cyclic monoterpenes including vanilin, pulegone, eugenole, carvone, carvacrol, carveol, thymol, thymoquinone, menthone, and limonene were investigated on the functional properties of the cloned alpha7 subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes. Monoterpenes inhibited the alpha7 nicotinic acetylcholine receptor in the order carveol>thymoquinone>carvacrol>menthone>thymol>limonene>eugenole>pulegone>=carvon >=vanilin. Among the monoterpenes, carveol showed the highest potency on acetylcholine-induced responses, with IC50 of 8.3uM. Carveol-induced inhibition was independent of the membrane potential and could not be reversed by increasing the concentration of acetylcholine. In line with functional experiments, docking studies indicated that cyclic monoterpenes such as carveol may interact with an allosteric site located in the alpha7 transmembrane domain. Our results indicate that cyclic monoterpenes inhibit the function of human alpha7 nicotinic acetylcholine receptors, with varying potencies. PMID- 26849940 TI - Dioscin suppresses human laryngeal cancer cells growth via induction of cell cycle arrest and MAPK-mediated mitochondrial-derived apoptosis and inhibition of tumor invasion. AB - The anti-cancer effects of dioscin have been widely reported. However, its effect on laryngeal cancer remains unknown. In the present paper, our results showed that dioscin markedly caused cell apoptosis and DNA damage, increased reactive oxygen species (ROS) level, induced S-phase arrest, and inhibited invasion of human laryngeal cancer HEp-2 and TU212 cells. Mechanism investigation showed that dioscin markedly up-regulated p53 level, and down-regulated cyclin-dependent kinase 2 (CDK2) and Cyclin A levels. In addition, dioscin significantly down regulated the levels of p-ERK, Bcl-2, up-regulated the levels of p-JNK, p-p38, Bax, cleaved caspase-3/-9, and caused Cytochrome c release. Furthermore, U0126, an ERK1/2 inhibitor, markedly down-regulated Bcl-2 level, up-regulated the levels of Bax, cleaved caspase-3/9, and enhanced Cytochrome c release inducted by dioscin. While, SP600125 (one JNK inhibitor) and SB203580 (one p38 inhibitor) markedly up-regulated Bcl-2 level, down-regulated the levels of Bax, cleaved caspase-3/9, and obviously boosted Cytochrome c release induced by dioscin. Interestingly, dioscin also markedly down-regulated the levels of MMP2 and MMP9 associated with tumor invasion. Taken together, our study indicated that dioscin suppressed laryngeal cancer cells growth via inducting cell-cycle arrest, MAPK mediated mitochondrial- derived apoptosis and inhibiting tumor invasion, which could be used as one potential candidate for the treatment of laryngeal cancer in the future. PMID- 26849941 TI - The therapeutic effects of tuberostemonine against cigarette smoke-induced acute lung inflammation in mice. AB - Chronic obstructive pulmonary disease (COPD) is mainly caused by cigarette smoking and is characterized by the destruction of lung parenchyma, structural alterations of the small airways, and systemic inflammation. Tuberostemonine (TS) is an alkaloid-type phytochemical from Stemona tuberosa. In the present study, we evaluated the anti-inflammatory effect of TS in a cigarette smoke (CS)-induced mouse model of acute lung inflammation. The mice were whole-body exposed to CS or fresh air for 7 days. TS was administered by an intraperitoneal (i.p.) injection 1h before exposure to CS. To test the effects of TS, the numbers of total cells, neutrophils, macrophages and lymphocytes in the bronchoalveolar lavage (BAL) fluid were counted. Furthermore, we measured the levels of several chemokines, such as GCP-2, MIP-3alpha, MCP-1 and KC, in the lung tissue. The cellular profiles and histopathological analysis demonstrated that the infiltration of peribronchial and perivascular inflammatory cells significantly decreased in the TS-treated groups compared with the CS-exposure group. The TS treatment significantly ameliorated the airway epithelial thickness induced by CS exposure and caused a significant decrement in the production of chemokines in the lung. These results suggest that TS has anti-inflammatory effects against CS-induced acute lung inflammation. PMID- 26849943 TI - Attenuation of neuropathic pain and neuroinflammatory responses by a pyranocoumarin derivative, anomalin in animal and cellular models. AB - The present study investigated the neuropathic pain, anti-neuroinflammatory and neuroprotective properties of a pyranocoumarin derivative (anomalin) in in vivo and in vitro models. An in vivo streptozotocin (STZ)-induced diabetic neuropathic pain model demonstrated that anomalin significantly suppressed neuropathic pain in mice. To identify the molecular mechanism of the anti-neuropathic pain activity of anomalin, sodium-nitroprusside (SNP)-induced neuroinflammation in neuro-2a (N2a) cells was further investigated in signaling pathways. The effects of anomalin against SNP-induced toxicity, nitrite production and related mRNA gene expression (iNOS and COX-2) were considerably reduced by anomalin in the SNP induced N2a cells. In the molecular signaling pathway, anomalin effectively blocked the SNP-induced activation of the IKKalpha/beta, IkappaBalpha, ERK1/2 and p38 MAPK pathways. Furthermore, anomalin remarkably reduced the increase in the SNP-induced nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. Additionally, the pro-inflammatory cytokines level was remarkably inhibited by anomalin in high glucose-induced DRG primary neurons and SNP-induced N2a cells. These findings indicate that anomalin has anti-neuropathic pain, anti neuroinflammatory and neuroprotective effects against STZ-induced diabetic type I neuropathic pain and SNP-induced in neuronal cell models via the inactivation of the NF-kappaB, Nrf2 and MAPK signaling pathways. PMID- 26849942 TI - Novel sulfamides and sulfamates derived from amino esters: Synthetic studies and anticonvulsant activity. AB - We report herein the design and optimization of a novel series of sulfamides and sulfamates derived from amino esters with anticonvulsant properties. The structures were designed based on the pharmacophoric pattern previously proposed, with the aim of improving the anticonvulsant action. The compounds were obtained by a new synthetic procedure with microwave assisted heating and the use of adsorbents in the isolation process. All the derivatives showed protection against the maximal electroshock seizure test (MES test) in mice at the lowest dose tested (30 mg/kg) but they did not show significant protection against the chemical induced convulsion by pentylenetetrazole. These results verify the ability of the computational model for designing new anticonvulsants structures with anti-MES activity. Additionally, we evaluated the capacity of the synthesized structures to bind to the benzodiazepine binding site (BDZ-bs) of the gamma-aminobutiric acid receptor (GABAA receptor). Some of them showed medium to low affinity for the BDZ-bs. PMID- 26849945 TI - Oxidative stress plays major role in mediating apoptosis in filarial nematode Setaria cervi in the presence of trans-stilbene derivatives. AB - Lymphatic filariasis, affecting around 120 million people in 80 countries worldwide, is an extremely painful disease and caused permanent and long term disability. Owing to its alarming prevalence there is immediate need for development of new therapeutics. A series of trans-stilbene derivatives were synthesized using aqueous reaction condition showing potential as antifilarial agents demonstrated in vitro. MTT reduction assay and dye exclusion test were performed to evaluate the micro and macrofilaricidal potential of these compounds. Amid 20 trans-stilbene derivatives together with Resveratrol (RSV), a multifunctional natural product was screened; nine compounds (28, 29, 33, 35, 36, 38, 39, 41 and 42) have showed promising micro and macrofilaricidal activities and four of them (28, 39, 41 and 42) showed better effectiveness than RSV. In the treated parasites apoptosis was established by DNA laddering, in situ DNA fragmentation and FACS analysis. The generation of ROS in the treated parasites was indicated by the depletion in the level of GSH, GR and GST activity and elevation of SOD, catalase, GPx activity and superoxide anion and H2O2 level. Along with the ROS generation and oxidative stress, the decreased expression of anti-apoptotic ced-9 gene and increased expression of nematode specific pro apoptotic genes, egl-1, ced-4 and ced-3 at the level of transcription and translation level; the up-regulation of caspase-3 activity and involvement of caspase-8,9,3, cytochrome-c and PARP were also observed and which denotes the probable existence of both extrinsic and intrinsic pathways apoptosis in parasitic nematodes. This observation is reported first time and thus it confirmed the mode of action and effectiveness of the compounds. Further, the comparative bioavailability-pharmacokinetics studies showed that compound 28 possesses comparable properties with Ivermectin. This study will certainly intensify our understanding of the pharmacological importance of trans-stilbenes as an anti-filarial agent. PMID- 26849944 TI - Up-regulation of Nrf2 is involved in FGF21-mediated fenofibrate protection against type 1 diabetic nephropathy. AB - The lipid lowering medication, fenofibrate (FF), is a peroxisome proliferator activated receptor-alpha (PPARalpha) agonist, possessing beneficial effects for type 2 diabetic nephropathy (DN). We investigated whether FF can prevent the development of type 1 DN, and the underlying mechanisms. Diabetes was induced by a single intraperitoneal injection of streptozotocin in C57BL/6J mice. Mice were treated with oral gavage of FF at 100mg/kg every other day for 3 and 6 months. Diabetes-induced renal oxidative stress, inflammation, apoptosis, lipid and collagen accumulation, and renal dysfunction were accompanied by significant decrease in PI3K, Akt, and GSK-3beta phosphorylation as well as an increase in the nuclear accumulation of Fyn [a negative regulator of nuclear factor (erythroid-derived 2)-like 2 (Nrf2)]. All these adverse effects were significantly attenuated by FF treatment. FF also significantly increased fibroblast growth factor 21 (FGF21) expression and enhanced Nrf2 function in diabetic and non-diabetic kidneys. Moreover, FF-induced amelioration of diabetic renal damage, including the stimulation of PI3K/Akt/GSK-3beta/Fyn pathway and the enhancement of Nrf2 function were abolished in FGF21-null mice, confirming the critical role of FGF21 in FF-induced renal protection. These results suggest for the first time that FF prevents the development of DN via up-regulating FGF21 and stimulating PI3K/Akt/GSK-3beta/Fyn-mediated activation of the Nrf2 pathway. PMID- 26849947 TI - Detrimental effects for colonocytes of an increased exposure to luminal hydrogen sulfide: The adaptive response. AB - Protein fermentation by the gut microbiota releases in the large intestine lumen various amino-acid derived metabolites. Among them, hydrogen sulfide (H2S) in excess has been suspected to be detrimental for colonic epithelium energy metabolism and DNA integrity. The first objective of this study was to evaluate in rats the epithelial response to an increased exposure to H2S. Experiments from colonocyte incubation and intra-colonic instillation indicate that low millimolar concentrations of the sulfide donor NaHS reversibly inhibited colonocyte mitochondrial oxygen consumption and increased gene expression of hypoxia inducible factor 1alpha (Hif-1alpha) together with inflammation-related genes namely inducible nitric oxide synthase (iNos) and interleukin-6 (Il-6). Additionally, rat colonocyte H2S detoxification capacity was severely impaired in the presence of nitric oxide. Based on the gammaH2AX ICW technique, NaHS did not induce DNA damage in colonocytes. Since H2S is notably produced by the gut microbiota from sulfur containing amino acids, the second objective of the study was to investigate the effects of a high protein diet (HPD) on large intestine luminal sulfide content and on the expression of genes involved in H2S detoxification in colonocytes. We found that HPD markedly increased H2S content in the large intestine but the concomitant increase of the content mass maintained the luminal sulfide concentration. HPD also provoked an increase of sulfide quinone reductase (Sqr) gene expression in colonocytes, indicating an adaptive response to increased H2S bacterial production. In conclusion, low millimolar NaHS concentration severely affects colonocyte respiration in association with increased expression of genes associated with intestinal inflammation. Although HPD increases the sulfide content of the large intestine, the colonic adaptive responses to this modification limit the epithelial exposure to this deleterious bacterial metabolite. PMID- 26849946 TI - Persister formation in Escherichia coli can be inhibited by treatment with nitric oxide. AB - Bacterial persisters are phenotypic variants that survive extraordinary concentrations of antibiotics, and are thought to underlie the propensity of biofilm infections to relapse. Unfortunately many aspects of persister physiology remain ill-defined, which prevents progress toward eradicating the phenotype. Recently, we identified respiration within non-growing Escherichia coli populations as a potential target for the elimination type I persisters, which are those that arise from passage through stationary phase. Here we discovered that nitric oxide (NO) treatment at the onset of stationary phase significantly reduced type I persister formation through its ability to inhibit respiration. NO decreased protein and RNA degradation in stationary phase cells, and produced populations that were more fit for protein synthesis and growth resumption upon introduction into fresh media than untreated controls. Overall, this data shows that NO, which is a therapeutically-relevant compound, has the potential to decrease the incidence of recurrent infections from persisters. PMID- 26849949 TI - Contrast Spread Technique: Evolution. PMID- 26849948 TI - Correlation Between DNA Methylation of TRPA1 and Chronic Pain States in Human Whole Blood Cells. AB - OBJECTIVES: Neuro-immune interactions with functional changes in the peripheral blood cells including changes in the transient receptor potential ankyrin 1 (TRPA1) appear to play a pivotal role in the development of chronic pain in humans. The aim of this study was to examine the association between TRPA1 DNA methylation in whole blood cells and the pain states in chronic pain patients. METHODS: After collecting blood samples from 12 chronic pain patients, the authors measured DNA methylation levels in whole blood cells. Significant associations between the patient's demographic data and the chronic pain states were determined by a multiple linear regression analysis that used age, body mass index, pain duration, depression, anxiety, cognitive impairment, activities of daily living, neuropathic pain, and pain states as the dependent variables, and the TRPA1 DNA methylation levels as the independent variables. RESULTS: Multiple regression analysis revealed a significant correlation between increases of the methylation levels of the CpG island in the TRPA1 gene and increases in the number of neuropathic pain symptoms, which were evaluated using the Douleur Neuropathique 4 (DN4) questionnaire. Decreases in the TRPA1 mRNA expression were also significantly related to increases in the DN4 score. The presence of a burning sensation, which is one of pain symptoms in the DN4 questionnaire, was significantly correlated with the increase in DNA methylation level of TRPA1. CONCLUSIONS: TRPA1 DNA methylation levels in whole blood cells appear to be associated with pain symptoms in chronic pain patients. PMID- 26849951 TI - Are antidepressants and psychotherapy equally effective in treating depression? A critical commentary. PMID- 26849950 TI - Comparative Analysis of Psychological, Hormonal, and Genetic Factors Between Burning Mouth Syndrome and Secondary Oral Burning. AB - OBJECTIVE: The objective of this study was to evaluate the association between psychological, hormonal, and genetic factors with the development of burning mouth syndrome (BMS) and secondary oral burning (SOB) in order to provide a better characterization and classification of these conditions. DESIGN: Cross sectional study. SETTING: Patients with complaints of mouth burning registered at the Oral Diagnostic Service of the Federal University of Rio Grande do Norte between 2000 and 2013. SUBJECTS: The sample consisted of 163 subjects divided into a group of patients with BMS (n = 64) and a group of subjects with SOB (n = 99). METHODS: The following variables were analyzed: passive and stimulated saliva flow, stress levels and phase, depression, anxiety, serum cortisol and dehydroepiandrosterone (DHEA) levels, and the presence of polymorphisms in the interleukin 6 (IL-6) gene. RESULTS: The results showed significant differences in the presence of xerostomia (p = 0.01), hyposalivation at rest (p < 0.001) and symptoms of depression (p = 0.033) between the two groups, which were more prevalent in the BMS group. DHEA levels were lower in the BMS group (p = 0.003) and were sensitive and specific for the diagnosis of this condition. Genetic analysis revealed no significant association between the polymorphisms analyzed and the development of BMS. CONCLUSION: These results suggest a possible role of depression, as well as of reduced DHEA levels, as associated factors for development of BMS. PMID- 26849952 TI - Investigation on the emission quality, performance and combustion characteristics of the compression ignition engine fueled with environmental friendly corn oil methyl ester - Diesel blends. AB - This paper deals with emission quality of diesel engine based on eco toxicological studies with different methods of environmental standard toxicity tests satisfy the Bharath and European emission norms. Based on the emission norms, Corn Oil Methyl Ester (COME) with diesel is tested in a compression ignition engine and the performance and combustion characteristics are discussed. The corn oil was esterified and the property of corn oil methyl ester was within the limits specified in ASTM D 6751-03. The COME was blended together with diesel in different proportion percentages along with B20, B40, B60, B80, and B100. The emission and performance tests for various blends of COME was carried out using single cylinder, four stroke diesel engine, and compared with the performance obtained with 100% diesel (D100). The results give clear information that COME has low exhaust emissions and increase in performance compared to D100 without any modifications. It gives better performance, which is nearer to the obtained results of D100. Specific Fuel Consumption (SFC) of B100 at the full load condition is found to be 4% lower than that of (D100). The maximum Brake Thermal Efficiency (BTE) of B100 is found to be 8.5% higher than that of the D100 at full load. Also, the maximum BTE of part load for different blends is varied from 5.9% to 7.45% which is higher than D100. The exhaust gas emissions like Carbon Monoxide (CO), Carbon Dioxide (CO2), Hydro Carbon (HC) and Nitrogen Oxide (NOx) are found to be 2.3 to 18.8% lower compared to D100 for part as well as full load. The heat release rate of biodiesel and it blends are found to 16% to 35% lower as compared to D100 for part load, where as for full load it is 21% lower than D100. The results showed that the test of emissions norms are well within the limits of Bharath VI and European VI and it leads to less pollution, less effect on green eco system and potential substitute to fossil fuels. PMID- 26849953 TI - Hashimoto's encephalopathy: A rare proteiform disorder. AB - Hashimoto's encephalopathy (HE) is a rare not well understood, progressive and relapsing multiform disease, characterized by seizures, movement disorders, subacute cognitive dysfunction, psychiatric symptoms and responsiveness to steroid therapy. The disorder is generally associated with thyroid diseases and the most common feature is the presence of anti-thyroperoxidase antibodies (TPOAb). Patients are usually euthyroid or mildly hypothyroid at presentation. All age groups can be affected. The pathophysiology is still unclear, especially the link between elevated serum TPOAb and the encephalopathy. Most reported cases occurred in women and girls. Unspecific symptoms, non-pathognomonic laboratory neurophysiology and neuroimaging features make its diagnosis a real challenge for clinicians. The case of a 16 year old boy, with a clinical picture of HE associated with hypothyroidism, demonstrating an excellent response to high dose steroids is presented together with a systematic review of the literature. PMID- 26849954 TI - Long-term biventricular HeartWare ventricular assist device support--Case series of right atrial and right ventricular implantation outcomes. AB - BACKGROUND: There is limited information on outcomes using the HeartWare ventricular assist device (HVAD; HeartWare, Framington, MA) as a biventricular assist device, especially with respect to site of right ventricular assist device (RVAD) implantation. METHODS: Outcomes in 13 patients with dilated cardiomyopathy and severe biventricular failure who underwent dual HVAD implantation as bridge to transplantation between August 2011 and October 2014 were reviewed. RESULTS: Of 13 patients, 10 were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Level 1, and 3 were INTERMACS Level 2. Mean age was 45 +/- 11 years, and mean body mass index was 26 +/- 4 kg/m(2). There were 7 patients on temporary mechanical support pre-operatively (extracorporeal life support, n = 5; intra-aortic balloon pump, n = 2). The median hospital length of stay was 53 days (interquartile range [IQR] 33-70 days) with a median intensive care unit length of stay of 14 days (IQR 8-36 days). The median length of support on device was 269 days (IQR 93-426 days). The right HVAD was implanted in the right ventricular (RV) free wall in 6 patients and in the right atrial (RA) free wall in 7 patients. Transplantation was successfully performed in 5 patients, and overall survival for the entire cohort was 54%. RVAD pump thrombosis occurred in 3 of 6 RV pumps and 1 of 7 RA pumps. No left ventricular assist device pump thrombosis was observed. Bleeding tended to be higher in the RV implantation group (3 of 6 vs 0 of 7). During follow up, 6 patients died (4 of 7 in the RA group vs 2 of 6 in the RV group). Cause of death was multiple-organ failure in 3 patients, sepsis in 2 patients, and intracerebral hemorrhage in 1 patient. CONCLUSIONS: Critically ill patients who require biventricular support can be successfully bridged to transplant using 2 HVADs. RA implantation may allow right heart support with lower pump thrombosis and bleeding complications, although this was at the expense of a higher mortality in this cohort. PMID- 26849955 TI - The numerical analysis of non-Newtonian blood flow in human patient-specific left ventricle. AB - Recently, various non-invasive tools such as the magnetic resonance image (MRI), ultrasound imaging (USI), computed tomography (CT), and the computational fluid dynamics (CFD) have been widely utilized to enhance our current understanding of the physiological parameters that affect the initiation and the progression of the cardiovascular diseases (CVDs) associated with heart failure (HF). In particular, the hemodynamics of left ventricle (LV) has attracted the attention of the researchers due to its significant role in the heart functionality. In this study, CFD owing its capability of predicting detailed flow field was adopted to model the blood flow in images-based patient-specific LV over cardiac cycle. In most published studies, the blood is modeled as Newtonian that is not entirely accurate as the blood viscosity varies with the shear rate in non-linear manner. In this paper, we studied the effect of Newtonian assumption on the degree of accuracy of intraventricular hemodynamics. In doing so, various non Newtonian models and Newtonian model are used in the analysis of the intraventricular flow and the viscosity of the blood. Initially, we used the cardiac MRI images to reconstruct the time-resolved geometry of the patient specific LV. After the unstructured mesh generation, the simulations were conducted in the CFD commercial solver FLUENT to analyze the intraventricular hemodynamic parameters. The findings indicate that the Newtonian assumption cannot adequately simulate the flow dynamic within the LV over the cardiac cycle, which can be attributed to the pulsatile and recirculation nature of the flow and the low blood shear rate. PMID- 26849956 TI - Putamen volume correlates with obsessive compulsive characteristics in healthy population. AB - Obsessions and compulsions (OCs) are frequent in healthy subjects; however neural backgrounds of the subclinical OCs were largely unknown. Results from recent studies suggested involvement of the putamen in the OC traits. To investigate this issue, 49 healthy subjects were assessed using structural magnetic resonance imaging (MRI) and the Maudsley Obsessive Compulsive Inventory (MOCI). Anatomical delineation on MRI yielded the global volume and local shape of the putamen. Other striatal structures (the caudate nucleus and globus pallidus) were also examined for exploratory purpose. The relationship between volume/shape of each structures and MOCI measure was analyzed, with sex, age, state anxiety, trait anxiety, and full-scale Intelligence Quotient regressed out. The volume analysis revealed a positive relationship between the MOCI total score and the bilateral putamen volumes. The shape analysis demonstrated associations between the higher MOCI total score and hypertrophy of the anterior putamen in both hemispheres. The present study firstly revealed that the volume changes of the putamen correlated with the manifestation of subclinical OC traits. The dysfunctional cortico anterior striatum networks seemed to be one of the neuronal subsystems underlying the subclinical OC traits. PMID- 26849958 TI - R76 in transmembrane domain 3 of the aspartate:alanine transporter AspT is involved in substrate transport. AB - The L-aspartate:L-alanine antiporter of Tetragenococcus halophilus (AspT) possesses an arginine residue (R76) within the GxxxG motif in the central part of transmembrane domain 3 (TM3)-a residue that has been estimated to transport function. In this study, we carried out amino acid substitutions of R76 and used proteoliposome reconstitution for analyzing the transport function of each substitution. Both l-aspartate and l-alanine transport assays showed that R76K has higher activity than the AspT-WT (R76), whereas R76D and R76E have lower activity than the AspT-WT. These results suggest that R76 is involved in AspT substrate transport. PMID- 26849957 TI - Clinical utility of multi-detector cardiac computed tomography in structural heart interventions. AB - In recent years, there have been major advances in structural interventional cardiology, which have revolutionized the practice of cardiology. Appropriate selection and follow-up of patients undergoing these structural heart interventions is vital. Multi-detector computed tomography (MDCT) has emerged as a key imaging modality in the peri-procedural assessment of patients undergoing multiple structural cardiac interventions. The purpose of this review is to provide an evidence-based clinical update on the roles of MDCT in both established and evolving structural heart interventions, including transcatheter aortic valve replacement (TAVR) and transcatheter mitral valve implantation (TMVI). The utility of MDCT in the peri-procedural assessment of patients undergoing pulmonary vein isolation (PVI) for atrial fibrillation, cardiac resynchronization therapy (CRT) and left atrial appendage (LAA) closure will also be reviewed. PMID- 26849959 TI - TGF-beta-induced profibrotic signaling is regulated in part by the WNT receptor Frizzled-8. AB - TGF-beta is important in lung injury and remodeling processes. TGF-beta and Wingless/integrase-1 (WNT) signaling are interconnected; however, the WNT ligand receptor complexes involved are unknown. Thus, we aimed to identify Frizzled (FZD) receptors that mediate TGF-beta-induced profibrotic signaling. MRC-5 and primary human lung fibroblasts were stimulated with TGF-beta1, WNT-5A, or WNT-5B in the presence and absence of specific pathway inhibitors. Specific small interfering RNA was used to knock down FZD8. In vivo studies using bleomycin induced lung fibrosis were performed in wild-type and FZD8-deficient mice. TGF beta1 induced FZD8 specifically via Smad3-dependent signaling in MRC-5 and primary human lung fibroblasts. It is noteworthy that FZD8 knockdown reduced TGF beta1-induced collagen Ialpha1, fibronectin, versican, alpha-smooth muscle (sm) actin, and connective tissue growth factor. Moreover, bleomycin-induced lung fibrosis was attenuated in FZD8-deficient mice in vivo Although inhibition of canonical WNT signaling did not affect TGF-beta1-induced gene expression in vitro, noncanonical WNT-5B mimicked TGF-beta1-induced fibroblast activation. FZD8 knockdown reduced both WNT-5B-induced gene expression of fibronectin and alpha-sm actin, as well as WNT-5B-induced changes in cellular impedance. Collectively, our findings demonstrate a role for FZD8 in TGF-beta-induced profibrotic signaling and imply that WNT-5B may be the ligand for FZD8 in these responses.-Spanjer, A. I. R., Baarsma, H. A., Oostenbrink, L. M., Jansen, S. R., Kuipers, C. C., Lindner, M., Postma, D. S., Meurs, H., Heijink, I. H., Gosens, R., Konigshoff, M. TGF-beta-induced profibrotic signaling is regulated in part by the WNT receptor Frizzled-8. PMID- 26849961 TI - Risk factors and outcomes of carbapenem-resistant Klebsiella pneumoniae infections in liver transplant recipients. PMID- 26849960 TI - Skeletal muscle PGC-1alpha modulates systemic ketone body homeostasis and ameliorates diabetic hyperketonemia in mice. AB - Ketone bodies (KBs) are crucial energy substrates during states of low carbohydrate availability. However, an aberrant regulation of KB homeostasis can lead to complications such as diabetic ketoacidosis. Exercise and diabetes affect systemic KB homeostasis, but the regulation of KB metabolism is still enigmatic. In our study in mice with either knockout or overexpression of the peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha in skeletal muscle, PGC-1alpha regulated ketolytic gene transcription in muscle. Furthermore, KB homeostasis of these mice was investigated during withholding of food, exercise, and ketogenic diet feeding, and after streptozotocin injection. In response to these ketogenic stimuli, modulation of PGC-1alpha levels in muscle affected systemic KB homeostasis. Moreover, the data demonstrate that skeletal muscle PGC-1alpha is necessary for the enhanced ketolytic capacity in response to exercise training and overexpression of PGC-1alpha in muscle enhances systemic ketolytic capacity and is sufficient to ameliorate diabetic hyperketonemia in mice. In cultured myotubes, the transcription factor estrogen-related receptor alpha was a partner of PGC-1alpha in the regulation of ketolytic gene transcription. These results demonstrate a central role of skeletal muscle PGC 1alpha in the transcriptional regulation of systemic ketolytic capacity. Svensson, K., Albert, V., Cardel, B., Salatino, S., Handschin, C. Skeletal muscle PGC-1alpha modulates systemic ketone body homeostasis and ameliorates diabetic hyperketonemia in mice. PMID- 26849962 TI - Purification and characterization of a novel extracellular alkaline protease from Cellulomonas bogoriensis. AB - An extracellular alkaline protease produced by the alkali-tolerant Cellulomonas bogoriensis was purified by a combination of ammonium sulfate precipitation and cation exchange chromatography. The purity of the protease was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its molecular weight was confirmed to be 18.3 kDa. The enzyme showed optimum activity at 60 degrees C and pH 11. The stability of the protease was maintained at a wide temperature range of 4-60 degrees C and pH range of 3-12. Irreversible inhibition of the enzyme activity by phenylmethylsulfonyl fluoride and tosyl-l-phenylalanine chloromethyl ketone demonstrated that the purified enzyme is a chymotrypsin of the serine protease family. The Km and Vmax of the protease activity on casein were 19.2 mg/mL and 25000 MUg/min/mg, respectively. The broad substrate specificity and remarkable stability in the presence of organic solvents, salt, and commercial detergents, as well as its excellent stain removal and dehairing capability, make the purified alkaline protease a promising candidate for industrial applications. PMID- 26849963 TI - Selection of suitable detergents for obtaining an active dengue protease in its natural form from E. coli. AB - Dengue protease is a two-component enzyme and is an important drug target against dengue virus. The protease activity and protein stability of dengue nonstructural protein 3 (NS3) require a co-factor region from a four-span membrane protein NS2B. A natural form of dengue protease containing full-length NS2B and NS3 protease domain NS2BFL-NS3pro will be useful for dengue drug discovery. In current study, detergents that can be used for protease purification were tested. Using a water soluble protease construct, 39 detergents were selected for both NS2B and NS2BFL-NS3pro purification. The results showed that 18 detergents were able to sustain the activity of the natural dengue protease and 11 detergents could be used for NS2B purification. The results obtained in this study will be useful for biochemical and biophysical studies on dengue protease. PMID- 26849964 TI - Georeferencing of deaths from sepsis in the city of Sao Paulo. AB - OBJECTIVE: The aim of the present study was to obtain information about deaths due to sepsis in Sao Paulo from 2004 to 2009 and their relationship with geographical distribution. METHODS: Causes of death, both main and secondary, were defined according to the codes of the International Classification of Disease version 10 (ICD-10) contained in the database. Sepsis, septic shock, multiple organ failure, pneumonia, urinary tract infection, peritonitis and other intraabdominal infections, skin and soft tissue infections (including surgical wound infection) and meningitis were considered as immediate cause of death or as the condition leading to the immediate cause of death related or associated to sepsis. RESULTS: In the analyzed period, there was a 15.3% increase in the absolute number of deaths from sepsis in Sao Paulo. The mean number of deaths during this period was 28,472+/-1566. Most deaths due to sepsis and sepsis related diseases over the studied period occurred in a hospital or health care facility, showing that most of the patients received medical care during the event that led to death. We observed a significant concentration of deaths in the most populous regions, tending more toward the center of the city. CONCLUSIONS: Georeferencing data from death certificates or other sources can be a powerful tool to uncover regional epidemiological differences between populations. Our study revealed an even distribution of sepsis all over the inhabited areas of Sao Paulo. PMID- 26849966 TI - 3D HPLC-MS with Reversed-Phase Separation Functionality in All Three Dimensions for Large-Scale Bottom-Up Proteomics and Peptide Retention Data Collection. AB - The growing complexity of proteomics samples and the desire for deeper analysis drive the development of both better MS instrument and advanced multidimensional separation schemes. We applied 1D, 2D, and 3D LC-MS/MS separation protocols (all of reversed-phase C18 functionality) to a tryptic digest of whole Jurkat cell lysate to estimate the depth of proteome coverage and to collect high-quality peptide retention information. We varied pH of the eluent and hydrophobicity of ion-pairing modifier to achieve good separation orthogonality (utilization of MS instrument time). All separation modes employed identical LC settings with formic acid-based eluents in the last dimension. The 2D protocol used a high pH-low pH scheme with 21 concatenated fractions. In the 3D protocol, six concatenated fractions from the first dimension (C18, heptafluorobutyric acid) were analyzed using the identical 2D LC-MS procedure. This approach permitted a detailed evaluation of the analysis output consuming 21* and 126* the analysis time and sample load compared to 1D. Acquisition over 189 h of instrument time in 3D mode resulted in the identification of ~14 000 proteins and ~250 000 unique peptides. We estimated the dynamic range via peak intensity at the MS(2) level as approximately 10(4.2), 10(5.6), and 10(6.2) for the 1D, 2D, and 3D protocols, respectively. The uniform distribution of the number of acquired MS/MS, protein, and peptide identifications across all 126 fractions and through the chromatographic time scale in the last LC-MS stage indicates good separation orthogonality. The protocol is scalable and is amenable to the use of peptide retention prediction in all dimensions. All these features make it a very good candidate for large-scale bottom-up proteomic runs, which target both protein identification as well as the collection of peptide retention data sets for targeted quantitative applications. PMID- 26849965 TI - Incidence of virulence determinants in clinical Enterococcus faecalis and Enterococcus faecium isolates collected in Bulgaria. AB - OBJECTIVES: To evaluate the prevalence of some virulence genes among 510 clinical Enterococcus spp. isolates and to assess the association of those genes with the species, infection site, and patient group (inpatients/outpatients). METHODS: Adhesins genes (aggregation substances agg and asa1 of Enterococcus faecalis and Enterococcus faecium, respectively), enterococcal surface protein (esp), endocarditis-specific antigen A (efaA), collagen-binding proteins (ace/acm)); invasins (hyaluronidase (hyl) and gelatinase (gelE)); cytotoxines (activation of cytolysin (cylA) in E. faecalis); and modulators of the host immunity and inflammation (enhanced expression pheromone (eep) in E. faecalis) were detected by polymerase chain reaction. RESULTS: The overall prevalence was: esp - 44.3%, agg/asa1 - 38.4%, ace/acm - 64.3%, efaA - 85.9%, eep - 69.4%, gelE - 64.3%, hyl - 25.1%, and cylA - 47.1%. E. faecalis isolates had significantly higher frequency of adhesin genes (esp and agg/asa1) and gelatinase in comparison to E. faecium. Multiple virulence genes in E. faecalis were significantly more prevalent than in E. faecium isolates. Domination of E. faecium with or without only one gene compared to the isolates of E. faecalis were found. Enterococcus spp. isolates obtained from outpatients compared to inpatients isolates had significantly higher frequency of agg/asa1, eep, gelE and cylA. Some adhesins genes (esp, agg/asa1 and efaA) had higher prevalence among the non-invasive Enterococcus spp. isolates compared to those causing invasive bacteremia, while ace/acm revealed higher dissemination in isolates causing invasive infections compared to non invasive isolates. CONCLUSION: Most E. faecalis attaches to abiotic surfaces in hospital environment, which correlates with higher prevalence of gene encoding for virulence factors involved in biofilm formation, such as enterococcal surface protein, aggregation substance, and gelatinase. The intestinal tract is an important reservoir for opportunistic enterococcal pathogens and allows them to access infectious sites through different virulence factors, demonstrated in outpatient isolates in this study. PMID- 26849967 TI - Complete genome sequence of a marine bacterium with two chromosomes, Pseudoalteromonas translucida KMM 520(T). AB - Bacteria with multiple chromosomes provide new insights into the evolution of multipartite genome structures and bacterial survival strategies. In this study, we report the complete genome sequence of Pseudoalteromonas translucida KMM 520(T), which contains two circular chromosomes and comprises 4,147,593 bp with a mean G+C content of 40.1%. The two chromosomes have similar G+C contents and similar percentages of coding regions. Chromosome II of P. translucida possesses a plasmid-type replication initiator protein (RepA), which indicated that chromosome II is probably originated from a plasmid. COG functional categories revealed that the two chromosomes have divergent distributions of functional categories, which indicated that they bear different responsibilities for cellular functions. The complete genome sequence of P. translucida contributes to a better understanding of the origin and evolution of the additional chromosome and the physiology of Pseudoalteromonas genus. PMID- 26849968 TI - The structure and morphogenic changes of antennae of Matsucoccus matsumurae (Hemiptera: Coccoidea: Matsucoccidae) in different instars. AB - To better understand the functioning and morphogenic changes of the antennae of Matsucoccus matsumurae (Kuwana) in different instars, the antennae are examined using light microscopy, scanning and transmission electron microscopy. The results show that the antennae of M. matsumurae display three different styles in morphology and sensillar distribution in different instars. The antennae of first instar nymphs are relatively simple, including one campaniform sensillum (Ca), four smooth aporous trichoid sensilla (SAt), two intersegmental sensilla (Ins), two coeloconic sensilla (Co), three multiporous pegs (Mp) and four uniporous pegs (Up). The antennae of adult females and third instar male nymphs both possess similar antennae, and exhibit seven types of sensilla. Adult female antennae have in total 82-108 sensilla, including 9-16 Bohm's bristle (Bb), 3-7 Ca, 50-75 SAt, 0-3 Ins, 3-10 Co, 8 Mp and 5 Up, whereas third instar male nymph antennae possess approximately 62-79 sensilla. Adult male antennae are the most developed, possessing 259-312 sensilla, including 7-15 Bb, 2-5 Ca, 7-11 grooved aporous trichoid sensilla, 4-9 SAt, 0-3 Ins, 2-7 Co, 23-29 knobbed seta sensilla, 179-230 multiporous trichoid sensilla and 8 Mp. Based on these results, the main functions and morphogenic changes of antennae M. matsumurae in different instars are discussed. PMID- 26849969 TI - Regulation of colorectal cancer cell epithelial to mesenchymal transition by the renin angiotensin system. AB - BACKGROUND AND AIM: Epithelial to mesenchymal transition (EMT) is implicated in tumor progression. We aimed to determine if the renin angiotensin system has a role in colorectal cancer (CRC) cell EMT. METHODS: Human CRC cell lines DLD-1 and LIM2405 were used in wound scratch migration assays where they were treated with renin angiotensin system peptide ANG II alone or with blockers of ANG II type 1 or 2 receptors (AT1R and AT2R). Levels of epithelial (E-cadherin), mesenchymal (ZEB1, Vimentin) markers, inducible nitric oxide synthase (iNOS), and MMP9 were determined by flow cytometry. Mice bearing CRC liver metastases and treated with blockers for AT1R or AT2R were examined for ZEB1 and iNOS by immunohistochemistry. RESULTS: ANG II increased in-vitro CRC cell migration in both cell lines, this was inhibited by AT1R (IRB) or AT2R blockade (PD123319). DLD-1 cells treated with AT1R blocker resulted in increased E-cadherin, reduced ZEB1, and Vimentin expression compared with ANG II-treated cells. Treatment with AT2R blocker decreased E-cadherin, no change in ZEB1 or Vimentin expression. AT1R blockade increased iNOS and decreased MMP9 expression in DLD-1 and LIM2405 cells. AT2R blockade decreased iNOS and MMP9 expression in both cell lines. In vivo, ZEB1 staining was higher in ANG II-treated animals compared with control and AT1R blockade treated animals, while activation of the AT2R led to an increase in iNOS compared with control and AT1R blockade. CONCLUSIONS: ANG II-induced migration of CRC cells via both AT1 and AT2 receptors; the AT1R-mediated effects were associated with changes typical of EMT. PMID- 26849970 TI - A novel local treatment for bleeding stomal varices. PMID- 26849971 TI - MicroRNA-145 Regulates Neural Stem Cell Differentiation Through the Sox2 Lin28/let-7 Signaling Pathway. AB - MicroRNAs (miRNAs or miRs) regulate several biological functions, including cell fate determination and differentiation. Although miR-145 has already been described to regulate glioma development, its precise role in neurogenesis has never been addressed. miR-145 represses sex-determining region Y-box 2 (Sox2), a core transcription factor of embryonic stem cells (ESCs), to inhibit pluripotency and self-renewal in human ESCs. In addition, the Sox2-Lin28/let-7 signaling pathway regulates proliferation and neurogenesis of neural precursors. In this study, we aimed to investigate the precise role of miR-145 in neural stem cell (NSC) fate decision, and the possible involvement of the Sox2-Lin28/let-7 signaling pathway in miR-145 regulatory network. Our results show for the first time that miR-145 expression significantly increased after induction of mouse NSC differentiation, remaining elevated throughout this process. Forced miR-145 downregulation decreased neuronal markers, namely betaIII-tubulin, NeuN, and MAP2. Interestingly, throughout NSC differentiation, protein levels of Sox2 and Lin28, a well-known suppressor of let-7 biogenesis, decreased. Of note, neuronal differentiation also resulted in let-7a and let-7b upregulation. Transfection of NSCs with anti-miR-145, in turn, increased both Sox2 and Lin28 protein levels, while decreasing both let-7a and let-7b. More importantly, Sox2 and Lin28 silencing partially rescued the impairment of neuronal differentiation induced by miR-145 downregulation. In conclusion, our results demonstrate a novel role for miR-145 during NSC differentiation, where miR-145 modulation of Sox2-Lin28/let-7 network is crucial for neurogenesis progression. Stem Cells 2016;34:1386-1395. PMID- 26849973 TI - Preface to the special issue "Hematopoiesis and immunity". PMID- 26849972 TI - Nurses' perceptions of care during wartime: a qualitative study. AB - AIM: This study explains nurses' experiences and views on the care of injured soldiers during the Iraq-Iran war (1980-1988) and the effect of this care on these nurses. BACKGROUND: Many studies on war suggest nurses' experiences physical and psychological trauma. Knowing the nurses' experiences can assist healthcare systems and the nursing profession to identify unknown threats. INTRODUCTION: War is a specific phenomenon. After soldiers, nurses are one of the first professions to engage in the phenomenon when it occurs. METHOD: A descriptive qualitative approach was used along with conventional content analysis. Data collected in 2014 from semi-structured interviews of 14 nurses who were selected through purposive sampling. RESULTS: Two themes (Care in the war, a different culture and concept and Care achievements during the war) and six subthemes (Unusual working conditions, Different work spirit, A real but informal classroom, Professional self-achievements, Outcomes for the professional community, The changed self) emerged from the data. CONCLUSION: A range of environmental factors and conditions, mental and emotional problems and the outcomes of war were identified. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study emphasizes the importance of being prepared for such crises and using the previous experiences of nurses who served in war time for training future nurses. PMID- 26849974 TI - Sexual satisfaction and inflammatory bowel diseases: an interdisciplinary clinical challenge. AB - Inflammatory bowel diseases (IBD), most commonly Crohn's disease and ulcerative colitis, have the highest incidence during the reproductive years. IBD and its treatments increase the risk of sexual dysfunction for both men and women with these diseases. Women with IBD often seek care from their gynecologist and may preferentially discuss sexual experiences with them over other providers. An understanding of IBD and its impact on sexual functioning and satisfaction will improve screening, evaluation, and management for these patients. Identifying interdisciplinary providers for referrals, such as pelvic floor physical therapists and health psychologists, is a key component to long-term improvements in sexual satisfaction for women with IBD. PMID- 26849975 TI - 'On-demand' romiplostim therapy in immune thrombocytopenia. AB - WHAT IS KNOWN AND OBJECTIVE: Although thrombopoietin receptor agonists are a second-line treatment for refractory immune thrombocytopenia (ITP), we lack guidelines recommending maintenance modality in patients who achieve complete remission (CR). CASE SUMMARY: We report a patient with refractory ITP who achieved CR on romiplostim. Obtaining romiplostim for 6 months of therapy, we decided to try extending this by modifying the standard treatment regimen. Romiplostim was successfully administered 'on-demand', only if the patient's platelet count dropped below 150 * 109 /L, over a period of 12 months. WHAT IS NEW AND CONCLUSION: The strategy of 'on-demand' therapy is a promising procedure for the maintenance of response, lowering costs and improving treatment safety. PMID- 26849976 TI - Thriving as AORN Members. PMID- 26849977 TI - Maintaining Ethics in Quality Improvement. PMID- 26849978 TI - A Few Minutes With Doreen Wagner. PMID- 26849980 TI - AORN Surgical Conference & Expo 2016 Speaker Interviews. PMID- 26849981 TI - Perioperative Care of the Transgender Patient. AB - Transgender patients are individuals whose gender identity is not related to their biological sex. Assuming a new gender identity that does not conform to societal norms often results in discrimination and barriers to health care. The exact number of transgender patients is unknown; however, these patients are increasingly seen in health care. Transgender individuals may experience provider generated discrimination in health care facilities, including refusal of service, disrespect, and abuse, which contribute to depression and low self-esteem. Transgender therapies include mental health counseling for depression and low self-esteem, hormone therapy, and sex reassignment surgery. Health care professionals require cultural competence, an understanding of the different forms of patient identification, and adaptive approaches to care for transgender patients. VA (Veterans Affairs) hospitals provide a model for the care for transgender patients and staff. PMID- 26849982 TI - OR Specimen Labeling. AB - Mislabeled surgical specimens jeopardize patient safety and quality care. The purpose of this project was to determine whether labeling surgical specimens with two patient identifiers would result in an 80% reduction in specimen labeling errors within six months and a 100% reduction in errors within 12 months. Our failure mode effects analysis found that the lack of two patient identifiers per label was the most unsafe step in our specimen handling process. We piloted and implemented a new process in the OR using the Plan-Do-Check-Act conceptual framework. The audit process included collecting data and making direct observations to determine the sustainability of the process change; however, the leadership team halted the direct observation audit after four months. The total number of surgical specimen labeling errors was reduced by only 60% within six months and 62% within 12 months; therefore, the goal of the project was not met. However, OR specimen labeling errors were reduced. PMID- 26849983 TI - ICD-10 Medical Coding: The Role of Perioperative Services in Addressing Implementation Challenges. AB - The International Classification of Diseases, 10th Revision (ICD-10) was adopted in the United States on October 1, 2015. Replacing the outdated ICD, Ninth Revision, Clinical Modification (ICD-9-CM) coding system was long overdue, and the updated classifications were needed to accurately collect data and improve patient care. However, the complexity of ICD-10 may present substantial challenges for health information management coders and affect hospital revenue collection. Because the OR generates a large share of a hospital's overall revenue, perioperative services personnel must take a critical look at ICD-10 changes and address adoption challenges to minimize the negative effects ICD-10 may have on surgical revenue and help personnel identify perioperative services' important role in ICD-10 implementation. PMID- 26849984 TI - Student Immersion in Perioperative Nursing. AB - The aging workforce and the lack of perioperative clinical practice and theoretical content in nursing education programs are factors contributing to the perioperative nursing shortage. This article discusses the implementation of a creatively designed perioperative program, which includes a didactic course and a 210-hour clinical course, developed by the faculty members of a Michigan school of nursing in collaboration with administrators at area hospitals. The didactic content covers materials presented during the first three months of orientation for newly employed perioperative nurses. Interested baccalaureate nursing students in their senior year are selected to participate in the program after being interviewed by hospital personnel and university faculty members. To date, the program has 18 student graduates in two semesters; all have been offered positions in the perioperative setting, and 14 have accepted positions. The active learning strategies used in the course are described with examples. PMID- 26849985 TI - Optimal Time to Surgery for Patients Requiring Laparoscopic Appendectomy: An Integrative Review. AB - Acute appendicitis is the most common condition requiring emergency surgery worldwide. Although current guidelines recommend prompt appendectomy as the preferred treatment, no time interval for surgery has been indicated. We used an integrative review methodology to critically evaluate evidence on the relationship between time to surgery and hospital length of stay and to identify the ideal time to surgery for patients undergoing appendectomy. We included 14 studies in our synthesis, most of which (n = 9/14, 64%) indicated that longer time delays to surgical intervention increased hospital length of stay for patients presenting with appendicitis. Researchers report that the optimal time for surgery is 24 to 36 hours after symptom onset, or 10 to 24 hours from admission. The results of our review indicate that patient symptoms on presentation may signify advancing pathology and may be more important than the time delay interval in defining surgical priority. PMID- 26849986 TI - Crisis Management of Unstable Bradycardia in the OR. PMID- 26849987 TI - Hospital-Acquired Pressure Ulcers in the Ambulatory Surgery Setting. PMID- 26849988 TI - Occupational Licensing Developments at the State Level for Nursing. PMID- 26849989 TI - Life After Accreditation: Keeping the Momentum Going. PMID- 26849990 TI - Nursing Considerations for the Patient With a Difficult Airway. PMID- 26849992 TI - Haste Makes Care Unsafe. PMID- 26849993 TI - Integrating Simulations Into Perioperative Education for Undergraduate Nursing Students. AB - Incorporating high-fidelity simulations into an undergraduate nursing program's perioperative elective course capitalizes on students' active learning. Simulations allow students the opportunity to assess and participate in clinical scenarios, apply standards, and demonstrate correct nursing actions without compromising patient safety. Incorporating a high-risk, low-volume malignant hyperthermia simulation experience into the undergraduate nursing curriculum emphasizes active learning and provides an opportunity for students to experience an uncommon emergency perioperative event. A high-fidelity malignant hyperthermia simulation links a scenario with course content, incorporates didactic information from previous courses, and emphasizes the importance of debriefing. PMID- 26849994 TI - Maintaining Perioperative Normothermia: Sustaining an Evidence-Based Practice Improvement Project. AB - Unintentional perioperative hypothermia has been shown to cause serious patient complications and, thus, to increase health care costs. In 2009, an evidence based practice improvement project produced a significant decrease in unintentional perioperative hypothermia in colorectal surgical patients through monitoring of OR ambient room temperature. Project leaders engaged all interdisciplinary stakeholders in the original project, which facilitated the sustainability of the intervention method. An important aspect of sustainability is ongoing monitoring and evaluation of a new intervention method. Therefore, continued evaluation of outcomes of the protocol developed in 2009 was scheduled at specific time points after the initial small test of change with colorectal patients. This article focuses on how attention to sustainability factors during implementation of an improvement project led to the sustainability of a protocol for monitoring OR ambient room temperature with all types of surgical patients five years after the initial project. PMID- 26849995 TI - Hydrothermal Preparation and Characterization of TiO2 /BiVO4 Composite Catalyst and its Photolysis of Water to Produce Hydrogen. AB - In the present work, bismuth vanadate composited photocatalysts were synthesized and characterized. X-ray diffractometry and Raman results showed that the particles were well crystallized, and formed by the complex of monoclinic BiVO4 and TiO2 . On electron microscopy, the photocatalyst exhibited high crystallization, agglutination and irregular shape, and was surrounded by numerous TiO2 particles. The study of surface areas showed that the specific surface area of 30-BiVO4 /TiO2 composited was 112 m(2) .g(-1) , which was nearly 10 times that of pure BiVO4 . The ultraviolet-visible diffuse reflectance spectra indicated the composited photocatalyst were activated in visible light. The activity of photocatalytic water splitting was studied. The results showed that monomer BiVO4 photocatalyst was not able to produce hydrogen under any light source. BiVO4 /TiO2 composited photocatalysts, however, were capable of generating hydrogen. Under UV light irradiation for 120 min, 1 g catalyst dispersed in 50 mL deionized water produced almost 1 mL hydrogen, such that the productivity of hydrogen was higher than that of P25-TiO2 . Photocatalytic decomposition of water under visible light also confirmed that the BiVO4 /TiO2 composited photocatalyst had the ability of water splitting. PMID- 26849996 TI - Motivational interviewing and self-determination theory in a web-based computer tailored physical activity intervention: A randomized controlled trial. AB - OBJECTIVE: This study explores whether a web-based physical activity (PA) intervention grounded in self-determination theory (SDT) and motivational interviewing (MI) is more effective and better appreciated than a traditional web based PA intervention. DESIGN: A randomized controlled trial was conducted, comparing (1) I Move; a web-based PA intervention based on SDT and MI, (2) Active Plus; a traditional web-based PA intervention and (3) a waiting list control condition. MAIN OUTCOME MEASURES: Weekly minutes of moderate to vigorous PA and weekly days with >=30 min PA were measured through self-report at baseline and at 3 and 6 months from baseline. RESULTS: I Move achieved a small, but significant increase in weekly minutes of moderate to vigorous PA, while Active Plus did not have a significant impact on this outcome. Both interventions were effective in increasing weekly days with >=30 min PA, whereas Active Plus yielded a greater effect on this outcome. CONCLUSION: Overall, the web-based PA intervention grounded in SDT and MI did not outperform the traditional web-based PA intervention. Further research should reveal whether this type of intervention is profitable for long-term maintenance of PA levels. PMID- 26849997 TI - Acute Effects of Lysergic Acid Diethylamide on Circulating Steroid Levels in Healthy Subjects. AB - Lysergic acid diethylamide (LSD) is a serotonin 5-hydroxytryptamine-2A (5-HT2A ) receptor agonist that is used recreationally worldwide. Interest in LSD research in humans waned after the 1970s, although the use of LSD in psychiatric research and practice has recently gained increasing attention. LSD produces pronounced acute psychedelic effects, although its influence on plasma steroid levels over time has not yet been characterised in humans. The effects of LSD (200 MUg) or placebo on plasma steroid levels were investigated in 16 healthy subjects using a randomised, double-blind, placebo-controlled, cross-over study design. Plasma concentration-time profiles were determined for 15 steroids using liquid chromatography tandem mass-spectrometry. LSD increased plasma concentrations of the glucocorticoids cortisol, cortisone, corticosterone and 11 dehydrocorticosterone compared to placebo. The mean maximum concentration of LSD was reached at 1.7 h. Mean peak psychedelic effects were reached at 2.4 h, with significant alterations in mental state from 0.5 h to > 10 h. Mean maximal concentrations of cortisol and corticosterone were reached at 2.5 h and 1.9 h, and significant elevations were observed 1.5-6 h and 1-3 h after drug administration, respectively. LSD also significantly increased plasma concentrations of the androgen dehydroepiandrosterone but not other androgens, progestogens or mineralocorticoids compared to placebo. A close relationship was found between plasma LSD concentrations and changes in plasma cortisol and corticosterone and the psychotropic response to LSD, and no clockwise hysteresis was observed. In conclusion, LSD produces significant acute effects on circulating steroids, especially glucocorticoids. LSD-induced changes in circulating glucocorticoids were associated with plasma LSD concentrations over time and showed no acute pharmacological tolerance. PMID- 26849998 TI - Intracortical Inhibition Assessed with Paired-Pulse Transcranial Magnetic Stimulation is Modulated during Shortening and Lengthening Contractions in Young and Old Adults. AB - BACKGROUND: The modulation of intracortical inhibition is thought to be impaired in older adults, which may contribute to their reduced fine motor control, particularly during lengthening muscle contractions. OBJECTIVE: To quantify the magnitude of intracortical inhibition and movement performance during postural, shortening and lengthening contractions of a hand muscle in young and old adults. METHODS: In 18 young (23.2 +/- 4.2) and 16 old (70.6 +/- 6.5) subjects, paired pulse transcranial magnetic stimulation (TMS) was used to assess short-interval intracortical inhibition (SICI) and long-interval intracortical inhibition (LICI) during a movement task involving the first dorsal interosseous muscle. The task required a constant load (50 g) to be slowly lifted and lowered using the index finger while single- or paired-pulse TMS was delivered during the shortening or lengthening contraction. RESULTS: Relative to postural contractions, SICI during shortening contractions was reduced by 29% in young subjects (P < 0.0001) and 43% in old subjects (P < 0.0001), whereas SICI during lengthening contractions was reduced by 11% in young subjects (P = 0.0004) and 33% in old subjects (P < 0.0001). Furthermore, SICI was significantly less in older adults during lengthening contractions (P-values < 0.01). For LICI, inhibition was not influenced by contraction type in old subjects, but was increased by 11% during shortening contractions (P < 0.0001) and by 9% during lengthening contractions in young subjects (P = 0.0008). In addition, old subjects showed significantly less LICI than young subjects in each movement phase (both P-values < 0.05). CONCLUSIONS: Shortening and lengthening contractions with a constant load are associated with a modulation of GABAergic inhibition that is altered by healthy ageing. PMID- 26849999 TI - Anodal Cerebellar Direct Current Stimulation Reduces Facilitation of Propriospinal Neurons in Healthy Humans. AB - BACKGROUND: Coordinated muscle synergies in the human upper limb are controlled, in part, by a neural distribution network located in the cervical spinal cord, known as the cervical propriospinal system. Studies in the cat and non-human primate indicate the cerebellum is indirectly connected to this system via output pathways to the brainstem. Therefore, the cerebellum may indirectly modulate excitability of putative propriospinal neurons (PNs) in humans during upper limb coordination tasks. OBJECTIVE/HYPOTHESIS: This study aimed to test whether anodal direct current stimulation (DCS) of the cerebellum modulates PNs and upper limb coordination in healthy adults. The hypothesis was that cerebellar anodal DCS would reduce descending facilitation of PNs and improve upper limb coordination. METHODS: Transcranial magnetic stimulation (TMS), paired with peripheral nerve stimulation, probed activity in facilitatory and inhibitory descending projections to PNs following an established protocol. Coordination was tested using a pursuit rotor task performed by the non-dominant (ipsilateral) hand. Anodal and sham DCS were delivered over the cerebellum ipsilateral to the non dominant hand in separate experimental sessions. Anodal DCS was applied to a control site lateral to the vertex in a third session. Twelve right-handed healthy adults participated. RESULTS: Pairing TMS with sub-threshold peripheral nerve stimulation facilitated motor evoked potentials at intensities just above threshold in accordance with the protocol. Anodal cerebellar DCS reduced facilitation without influencing inhibition, but the reduction in facilitation was not associated with performance of the pursuit rotor task. CONCLUSIONS: The results of this study indicate dissociated indirect control over cervical PNs by the cerebellum in humans. Anodal DCS of the cerebellum reduced excitability in the facilitatory descending pathway with no effect on the inhibitory pathway to cervical PNs. The reduction in PN excitability is likely secondary to modulation of primary motor cortex or brainstem nuclei, and identifies a neuroanatomical pathway for the cerebellum to assist in coordination of upper limb muscle synergies in humans. PMID- 26850000 TI - The complexities of simple technologies: re-imagining the role of rapid diagnostic tests in malaria control efforts. AB - BACKGROUND: Malaria rapid diagnostic tests (RDTs) are assumed to be simple-to-use and mobile technologies that have the capacity to standardize parasitological diagnosis for malaria across a variety of clinical settings. In order to evaluate these tests, it is important to consider how such assumptions play out in practice, in everyday settings of clinics, health centres, drug stores and for community health volunteers. METHODS: This paper draws on qualitative research on RDTs conducted over the last nine years. In particular the study reports on four qualitative case studies on the use of RDTs from Uganda, Tanzania and Sierra Leone, including qualitative interviews, focus group discussions and participant observation. RESULTS: Results suggest that while RDTs may be simple to use as stand-alone technological tools, it is not trivial to make them work effectively in a variety of economically pressured health care settings. The studies show that to perform RDTs effectively might very well need exactly the infrastructure they were designed to substitute: the medical expertise, organizational capacity and diagnostic and treatment options of well-funded and functioning health systems. CONCLUSIONS: These results underline that successful malaria diagnosis and treatment requires as much investment in general health infrastructure as it does in new technologies. PMID- 26850001 TI - Pedicle screw fixation and posterior fusion for lumbar degenerative diseases: effects on individual paraspinal muscles and lower back pain; a single-center, prospective study. AB - BACKGROUND: To the best of our knowledge, there have been no reports on the points at which the denervated multifidus and erector spinae muscles become reinnervated after pedicle screw fixation and posterior fusion in patients with lumbar degenerative diseases. Our study was designed to confirm reinnervation of denervated paraspinal muscles following pedicle screw fixation and posterior fusion and to confirm alleviation of the patients' lower back pain (LBP). METHODS: In this prospective study, we enrolled 67 patients who had undergone pedicle screw fixation and posterior fusion. The surgery had alleviated their leg pain, but the patients complained of LBP at the L3-5 level 3 months after the surgery. The patients were divided into two groups (I and II) according to the level at which pain was experienced. Paraspinal mapping scores were recorded preoperatively and 3, 6, 12, and 18 months postoperatively. Oswestry Disability Index and visual analogue scale scores were determined. Regression analyses using a general linear model and a mixed model were performed. RESULTS: Pedicle screw fixation and posterior fusion significantly denervated the multifidus and erector spinae not only in the surgical segment, but also in adjacent segments. Group I patients displayed reinnervation in the denervated erector spinae and multifidus muscles at 12 and 18 months, respectively. In contrast, group II showed reinnervation only in of the denervated erector spinae of the upper segment at 18 months, with no other areas of reinnervation. Postoperative LBP was significantly diminished at 12 months in group I and at 18 months in group II. There was also significantly less LBP at 6 months (prior to reinnervation of the paraspinal muscles). CONCLUSIONS: The denervated multifidus and erector spinae muscles at L4 5, which had been denervated using pedicle screw fixation and posterior fusion, were significantly reinnervated at 18 months postoperatively, whereas patients with denervation at L3-5 had only a tendency to be reinnervated at follow-up. Postoperative LBP in these patients was significantly diminished at the follow-up visits. PMID- 26850002 TI - Reluctance to care for patients with HIV or hepatitis B / C in Japan. AB - BACKGROUND: Healthcare workers are faced with various professional dilemmas in the workplace, including at times, a reluctance to care for particular patients. This study investigated personal attitudes and factors influencing Japanese nurses' reluctance to care for patients infected with HIV, Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV). METHODS: Participants completed an anonymous online survey focusing on potential attitudes towards hypothetical patients, awareness of infection risk and their confidence in using precautions to prevent infection. Statistical associations were analyzed using Poisson regression models. RESULTS: Regarding personal attitudes, 41% and 18% of nurses agreed or somewhat agreed that they would be reluctant to care for a hypothetical patient infected with HIV or HBV / HCV, respectively. Reluctance to care for patients with HIV or HBV / HCV was positively associated with prejudicial attitudes and negatively associated with confidence in personal safety precautions. Hypothetical reluctance to care for patients with HBV / HCV was negatively associated with actual previous experience caring for HBV / HCV patients. Older age among nurses (>=50 years) was positively associated with an increased reluctance to care for hypothetical patients with HIV. CONCLUSIONS: Overall, this study suggests that anxiety arising from perceived infection risk and having a prejudicial attitude might affect the acceptance of infected patients, while personal confidence in universal precautions probably mitigates this situation. Improving nurses' confidence in using universal precautions therefore represents a positive measure that can help reduce prejudice and improve the quality of healthcare services in Japan, as elsewhere. PMID- 26850003 TI - Discovery of silyl proline containing HCV NS5A inhibitors with pan-genotype activity: SAR development. AB - HCV NS5A inhibitors have shown impressive in vitro potency profiles in HCV replicon assays thus making them attractive components for inclusion in an all oral fixed dose combination treatment regimen. Herein we describe the research efforts that led to the discovery of silyl proline containing HCV NS5A inhibitors such as 7e and 8a with pan-genotype activity profile and acceptable pharmacokinetic properties. PMID- 26850004 TI - Syntheses and biological evaluation of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib. AB - Three novel series of 1,2,3-triazole and 1,3,4-oxadiazole derivatives of imatinib were prepared and evaluated in vitro for their cytostatic effects against a human chronic myeloid leukemia (K562), acute myeloid leukemia (HL60), and human leukemia stem-like cell line (KG1a). The structure-activity relationship was analyzed by determining the inhibitory rate of each imatinib analog. Benzene and piperazine rings were necessary groups in these compounds for maintaining inhibitory activities against the K562 and HL60 cell lines. Introducing a trifluoromethyl group significantly enhanced the potency of the compounds against these two cell lines. Surprisingly, some compounds showed significant inhibitory activities against KG1a cells without inhibiting common leukemia cell lines (K562 and HL60). These findings suggest that these compounds are able to inhibit leukemia stem-like cells. PMID- 26850006 TI - Anti-inflammatory and antioxidant properties of a novel resveratrol-salicylate hybrid analog. AB - Resveratrol is a natural compound with a plethora of activities as well as limitations. We recently reported a series of resveratrol-salicylate analogs with potential chemopreventive activity. Herein, we report the anti-inflammatory and antioxidant properties of these resveratrol derivatives. Using an in vitro COX inhibition assay, and two in vivo protocols (carrageenan-induced peritonitis and paw edema), we identified a novel compound (C10) as a potent anti-inflammatory agent. The enhanced potency of C10 was associated with the ability of C10 to decrease the activity of myeloperoxidase (MPO) enzyme at 10mg/kg, whereas resveratrol and it's natural analog (TMS) did not exert the same effect. Additionally, C10 significantly reduced the concentration of intracellular reactive oxygen species. Because of the proven association between cancer, inflammation, and oxidative stress, we believe that C10 is a promising chemopreventive molecule. PMID- 26850005 TI - Arylboronic acids as dual-action FAAH and TRPV1 ligands. AB - A series of 31 arylboronic acids designed on the basis of the pharmacophore model for a variety of TRPV1 antagonists was prepared and tested on FAAH and TRPV1 channel. Four of them, that is, compounds 3c, 4a, 5a,b acted as dual FAAH/TRPV1 blockers with IC50 values between 0.56 and 8.11MUM whereas ten others (compounds 1c,f-i, 2c-f, 4b) inhibited FAAH and activated/desensitized TRPV1. PMID- 26850007 TI - Genomic alterations of the JAK2 and PDL loci occur in a broad spectrum of lymphoid malignancies. AB - The recurrent 9p24.1 aberrations in lymphoid malignancies potentially involving four cancer-related and druggable genes (JAK2, CD274/PDL1, PDCD1LG2/PDL2, and KDM4C/JMJD2Cl) are incompletely characterized. To gain more insight into the anatomy of these abnormalities, at first we studied 9p24.1 alterations in 18 leukemia/lymphoma cases using cytogenetic and molecular techniques. The aberrations comprised structural (nine cases) and numerical (nine cases) alterations. The former lesions were heterogeneous but shared a common breakpoint region of 200 kb downstream of JAK2. The rearrangements predominantly targeted the PDL locus. We have identified five potential partner genes of PDL1/2: PHACTR4 (1p34), N4BP2 (4p14), EEF1A1 (6q13), JAK2 (9p24.1), and IGL (22q11). Interestingly, the cryptic JAK2-PDL1 rearrangement was generated by a microdeletion spanning the 3'JAK2-5'PDL1 region. JAK2 was additionally involved in a cytogenetically cryptic IGH-mediated t(9;14)(p24.1;q32) found in two patients. This rare but likely underestimated rearrangement highlights the essential role of JAK2 in B-cell neoplasms. Cases with amplification of 9p24.1 were diagnosed as primary mediastinal B-cell lymphoma (five cases) and T-cell lymphoma (four cases). The smallest amplified 9p24.1 region was restricted to the JAK2-PDL1/2-RANBP6 interval. In the next step, we screened 200 cases of classical Hodgkin lymphoma by interphase FISH and identified PDL1/2 rearrangement (CIITA- and IGH-negative) in four cases (2%), what is a novel finding. Forty (25%) cases revealed high level amplification of 9p24.1, including four cases with a selective amplification of PDL1/2. Altogether, the majority of 9p24.1 rearrangements occurring in lymphoid malignancies seem to target the programmed death-1 ligands, what potentiates the therapeutic activity of PD-1 blockade in these tumors. (c) 2016 Wiley Periodicals, Inc. PMID- 26850008 TI - Relative frontal brain asymmetry and cortisol release after social stress: The role of action orientation. AB - Social evaluation is a potent stressor and consistently leads to an activation of the hypothalamic-pituitary-adrenal system. Here, we investigated whether individual differences in action orientation influence the relationship between the cortisol response to social-evaluative threat and relative left frontal electroencephalographic (EEG) alpha asymmetry as a brain marker of approach motivation. Forty-nine participants were exposed to a camera-based variant of the Trier Social Stress Task while salivary cortisol and resting EEG frontal alpha asymmetry were assessed before and after stress induction. Higher relative left frontal activity was associated with higher changes in cortisol levels as measured by the area under curve with respect to increase, particularly in individuals low in action orientation. We discuss the role of the left frontal cortex in coping, the potential role of oxytocin, and negative health consequences when the left-frontal coping process becomes overstrained. PMID- 26850009 TI - Experimental Support for the Ecoimmunity Theory: Distinct Phenotypes of Nonlymphocytic Cells in SCID and Wild-Type Mice. AB - Immune tolerance toward "self" is critical in multiple immune disorders. While there are several mechanisms to describe the involvement of immune cells in the process, the role of peripheral tissue cells in that context is not yet clear. The theory of ecoimmunity postulates that interactions between immune and tissue cells represent a predator-prey relationship. A lifelong interaction, shaped mainly during early ontogeny, leads to selection of nonimmune cell phenotypes. Normally, therefore, nonimmune cells that evolve alongside an intact immune system would be phenotypically capable of evading immune responses, and cells whose phenotype falls short of satisfying this steady state would expire under hostile immune responses. This view was supported until recently by experimental evidence showing an inferior endurance of severe combined immunodeficiency (SCID) derived pancreatic islets when engrafted into syngeneic immune-intact wild-type (WT) mice, relative to islets from WT. Here we extend the experimental exploration of ecoimmunity by searching for the presence of the phenotypic changes suggested by the theory. Immune-related phenotypes of islets, spleen, and bone marrow immune cells were determined, as well as SCID and WT nonlymphocytic cells. Islet submass grafting was performed to depict syngeneic graft functionality. Islet cultures were examined under both resting and inflamed conditions for expression of CD40 and major histocompatibility complex (MHC) class I/II and release of interleukin-1alpha (IL-1alpha), IL-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), IL-10, and insulin. Results depict multiple pathways that appear to be related to the sculpting of nonimmune cells by immune cells; 59 SCID islet genes displayed relative expression changes compared with WT islets. SCID cells expressed lower tolerability to inflammation and higher levels of immune-related molecules, including MHC class I. Accordingly, islets exhibited a marked increase in insulin release upon immunocyte depletion, in effect resuming endocrine function that was otherwise suppressed by resident immunocytes. This work provides further support of the ecoimmunity theory and encourages subsequent studies to identify its role in the emergence and treatment of autoimmune pathologies, transplant rejection, and cancer. PMID- 26850010 TI - [Anti-angiogenic effect of interferon on JAK2V617F positive myeloproliferative neoplasms and its anti-angiogenic mechanisms]. AB - OBJECTIVE: To research the suppressive effect of interferon alpha2b (IFN-alpha2b) on angiogenesis of JAK2 tyrosine kinase gene point mutation (JAK2V617F) positive myeloproliferative neoplasm (MPN) and its anti-angiogenic mechanisms. METHODS: (1) A total of 42 cases of JAK2V617F positive MPN patients in the No.1 Hospital of Baoding were selected between January 2012 and October 2014, including the newly diagnosed group before treatment (n=25) and the IFN-alpha2b treatment group (n=17). Ten cases of idiopathic immune thrombocytopenic purpura (ITP) patients were enrolled as controls. JAK2V617F/JAK2 ratio was detected by real-time fluorescent quantitative PCR to measure mutation; the expression levels of phosphorylated JAK2 (p-JAK2), vascular endothelial growth factor (VEGF), hypoxia inducible factor-1alpha (HIF-1alpha) and CD105 marked microvascular density (MVD) in bone marrow were detected by immunohistochemistry. The correlations were analyzed among JAK2V617F mutation burden and VEGF, HIF-1alpha, and MVD. (2) Human erythroleukemia cell line HEL cells were treated with different concentrations of IFN-alpha2b. The apoptosis was detected by Hoechst staining method. The cell viability was detected by CCK-8 test. Cell migration ability was tested by transwell chambers. The protein expression levels of p-JAK2, VEGF, and HIF-1alpha were detected by Western blot. RESULTS: (1)The ratio of JAK2V617F/JAK2 in the IFN alpha2b treatment group (22.69% +/- 12.64%) was significantly lower than that in the newly diagnosed group (46.17% +/- 19.32%) (P<0.01). The expression levels of p-JAK2, VEGF, and HIF-1alpha in the newly diagnosed group (82.41% +/- 11.65%, 64.72% +/- 25.01%, 45.12% +/- 20.28%) were significantly higher than those in the IFN-alpha2b treatment group (60.93% +/- 20.57%, 36.58% +/- 15.95%, 32.15% +/- 14.27%) and the control group (43.05% +/- 12.59%, 25.69%+/- 1 3.75%, 25.07% +/- 15.49%) (all P<0.01). MVD in the newly diagnosed group (26.58% +/- 5.93%) was significantly higher than that in the treatment group (15.86%+/- 4.27%) and the control group (10.76% +/- 4.01%) (P<0.01). Spearman correlation analysis showed positive correlation of JAK2V617F mutation with VEGF and MVD (r=0.589, P<0.05; r=0.577, P<0.05). (2)The apoptosis of HEL cells were increased after treated with 30 000 U/L of IFN-alpha2b in HEL cells after 24 h. The proliferation of HEL cell were inhibited by different concentrations of IFN-alpha2b in time- and dose dependent manner. The number of membrane-permeating HEL cells after treated with 5 000 U/L of IFN-alpha2b in HEL cells after 24 h was significantly lower than that in the untreated cells (52.9 +/- 7.5 vs 77.3 +/- 6.1) (P<0.05). The expression levels of p-JAK2, VEGF, and HIF-1alpha were decreased in a dose dependent manner. CONCLUSION: IFN-alpha2b may exert an anti-angiogenic effect by inhibiting the VEGF, HIF-1alpha, and MVD expression in MPN via JAK2 signal pathway. PMID- 26850011 TI - [Value of three capsular antigen detection methods in diagnosis and efficacy assessment in patients with cryptococcal meningoencephalitis]. AB - OBJECTIVE: To assess the value of different kinds of cryptococcal capsular antigen detection methods in diagnosis and efficacy assessment in the patients with cryptococcal meningoencephalitis. METHODS: From October 2012 to March 2015, cerebrospinal fluid (CSF) samples were collected from 57 patients withcentral nervous system infection who hospitalized in Sir Run Run Shaw Hospital. The cryptococcal capsular antigen in CSF was detected by Lateral flow assay (LFA), Latex agglutination test(LA) and Enzyme immunoassay (EIA). Follow-up study was achieved in 10 patients by detecting the samples of their CSF using LA and EIA, so that the dynamic changes of the antigen level could be obtained and observed during the treatment. RESULTS: The sensitivity of LFA and LA were both 95%, meanwhile the specificity were both 100%; the sensitivity and specificity of EIA were both 100%. The level of cryptococcal capsular polysaccharide antigen decreased gradually with patients recovering. CONCLUSIONS: All the three different methods could beof great importance for the early diagnosis of cryptococcal meningoencephalitis. LFA should be recommended for screening the disease. Follow-up study by detecting the antigen level of CSF is valued in assessing the treatment efficacy of cryptococcal diseases. PMID- 26850012 TI - [Expression of miRNA-4497 in human chorionic villi from early recurrent miscarriage and the influence on apoptosis]. AB - OBJECTIVE: To investigate the expression of miRNA-4497 in human chorionic villi from early recurrent miscarriage and the influence on apoptosis. METHODS: The expression of miRNA-4497 in chorionic villi tissues collected from 20 early recurrent miscarriage cases and 20 controls were analyzed using quantitative real time polymerase chain reaction (qRT-PCR). Human BeWo trophoblastic strains transfected with miRNA-4497 mimic were collected before transfection and 24 h later to measure apoptosis by flow cytometry. RESULTS: miRNA-4497 was up regulated in early recurrent miscarriage (24.5% +/- 5.5% vs 1.1% +/- 0.1%, P<0.05), and there was significantly increase in apoptosis after miRNA-4497 mimic transfection (12.2% +/- 2.2% vs 7.3% +/- 1.2%, P<0.05). CONCLUSIONS: Up regulation of miR-4497 may play an important role in the pathogenesis of recurrent miscarriage. And the pathophysiological mechanism involved should be further studied. PMID- 26850013 TI - [Value of the Geriatric Nutritional Risk Index in predicting mortality of elderly patients undergoing hemodialysis]. AB - OBJECTIVE: To explore the reliability of the Geriatric Nutritional Risk Index (GNRI) as a mortality predictor in elderly patients undergoing hemodialysis (HD). METHODS: A total of 125 maintenance HD patients aged >60 years old who had received dialysis for over 6 months before entry was retrospectively examined. The values of GNRI were calculated, and death was taken as the end point. The patients were divided into 4 groups according to the quartiles of GNRI values. All-cause and cardiovascular mortality were calculated using Kaplan-Meier and cox proportional-hazards analyses, and ROC curve was adopted for analyzing the predicting value of GNRI on mortality. RESULTS: The GNRI of the four groups were <=92.06, 92.07-96.15, 96.16-101.25, >=101.26, respectively. Kaplan-Meier survival rate was significantly different among 4 groups for all-cause and cardiovascular mortality. Cox regression model analysis demonstrated that the GNRI was a predictor for all cause (HR=0.940, P=0.001, 95%CI: 0.907-0.974) and cardiovascular mortality (HR=0.906, P<0.001, 95%CI: 0.863-0.951). The area under ROC curve was 0.667 (P=0.001) for all-cause mortality and 0.717 (P=0.001) for cardiovascular mortality. CONCLUSION: The GNRI is a reliable predictor for all cause mortality in maintainance HD patients, but more multi-center studies with larger samples are still needed. PMID- 26850014 TI - [Correlation anslysis of sporadic breast cancer and BRCA1 gene plymorphisms in the Han Nationality and the Mongol Nationality of Inner Mongolia Region]. AB - OBJECTIVE: To study the correlationship between the BRCA1 gene polymorphisms, especially in 2731 loci (rs799917), and sporadic breast cancer in the Han nationality and the Mongol nationality of the Inner Mongolia region. METHODS: Using the prospective study method, 103 cases of patients with sporadic breast cancer (case group) and 103 cases of normal physical examination people (control group) were enrolled. PCR and direct sequencing method were used for analyzing the correlationship of 2731 loci polymorphisms of BRCA1 and sporadic breast cancer in our zone. RESULTS: In the case group, the age stratification, pathologic stage, immunohistochemistry and the distribution of lymph node metastasis had no significant difference in two ethnic group (P> 0.05). The age stratification of control group also had no significant difference in two ethnic group (P>0. 05). There was no statistically significant difference in age stratification of the case group and the control group (P>0.05). In the Inner Mongolia region, BRCA1 gene 2731 loci genotypes check out three genotypes: namely TT, CT and CC. The frequencies of genotype TT, CT, CC in the case group were 13.1%, 26.2%, 60.7% ( the Han nationality) and 16.7%, 28.6%, 54.7% (the Mongol nationality), respectively. Meanwhile the frequencies of allele T and allele C were 71.8% and 28.2%. In the control group, the frequencies of genotype TT, CT, CC were 18.0%, 31.1%, 50.9% ( the Han nationality) and 23.8%, 38.1%, 38.1% ( the Mongol nationality), respectively, and the frequencies of allele T and allele C were 62.9% and 37.1%. BRCA1 gene 2 731 loci gene polymorphism had no significant difference in two groups (chi(2)=3.438, P=0.752), but T allele frequency distribution in the case group was significantly increased (chi(2)=4.185, P=0.041). CONCLUSION: There is no obvious correlation between the BRCA1 gene 2731 loci and sporadic breast cancer in the Han nationality and the Mongol nationality of the Inner Mongolia region. C allele of BRCA1 gene 2731 loci may be one of the protective gene of sporadic breast cancer. PMID- 26850016 TI - [Effect of three-dimensional acellular fibrotic lung matrices on fibroblast-to myofibroblast differentiation]. AB - OBJECTIVE: To explore the effect of three-dimensional (3D) and two-dimensional (2D) acellular fibrotic lung matrices on fibroblast-to-myofibroblast differentiation. METHODS: Twenty adult SD rats were randomly divided into control group and idiopathic pulmonary fibrosis (IPF) group. The pulmonary fibrosis was induced by Bleomycin. Normal and fibrotic decellularized lungs were made, then sections with 500 um (3D) and 10 um (2D) thick were cut by a standard Vibratome. The lung fibroblasts were isolated from the lungs of SD rats at postnatal day 1, which were seeded dropwise into different slices (2D/3D normal and fibrotic scaffolds), then cultured for 72 hours in vitro. The protein expression of alpha smooth muscle actin (alpha-SMA) was measured by immunofluorescence staining and western blot. RESULTS: There was no spatial structure both in 2D normal scaffold and fibrotic scaffold. The spatial structure was different between 3D normal scaffold and fibrotic scaffold. The relative expression amount of alpha-SMA in 2D normal and fibrotic scaffold group and none scaffold group were (4.64 +/- 0.36, 4.86 +/- 0.37, 4.67 +/- 0.35, respectively), there were no difference among them (P>0.05). In 3D fibrotic scaffold group, the relative expression amount of alpha SMA was significantly increased compared with those in 3D normal scaffold group and 2D fibrotic scaffold group (6.29 +/- 0.85 vs 4.85 +/- 0.56, 4.86 +/- 0.37, both P<0.05). CONCLUSION: 3D acellular fibrotic lung scaffold can promote fibroblast-to-myofibroblast differentiation. PMID- 26850015 TI - [Lymphomatoid papulosis: a clinicopathologic study of 22 cases]. AB - OBJECTIVE: To investigate the clinical presentation, histopathological features, progression, and treatment of lymphomatoid papulosis (LyP). METHODS: A retrospective review was performed on clinicopathological data of 22 patients diagnosed with LyP from June 2010 to March 2015 in Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College. RESULT: The mean age of the 22 LyP patients was 39 years (range: 7-83 years). The male-to female ratio was 1:1. The areas predominantly affected were the trunks, followed by limbs and face. Most lesions presented as recurrent eruption of erythema, papule, nodules, ulcer, necrosis and crusting. Some of them leaved hyperpigmentation or atrophic scars on healing. Histopathologically, LyP were devided into types A, B, C, D and E, with 12, 1, 1, 3, and 4 cases in each type, respectively, and one case of mixed type B and C. One of the patients was also diagnosed with primary cutaneous anaplastic large-cell lymphoma besides the diagnosis of LyP. Among the 15 patients with follow-up information available, 11 patients were treated with regimens including oral corticosteroids, methotrexate, tripchlorolide, intramuscular injection of interferon, phototherapy, and topical corticosteroids. The mean follow-up time was 22 (1-54) months.All the patients were alive at the end of the follow-up period. CONCLUSIONS: LyP is a low-grade malignant T-cell lymphoma with a benign clinical course but histologically malignant features. Multi-agent chemotherapy is unnecessary. Patients with LyP are likely to have an favorable prognosis. PMID- 26850017 TI - [Related research between acute inflammatory reaction and hemodynamic changes of pulmonary embolism rabbit with hyperhomocysteinemia]. AB - OBJECTIVE: To explore the association between acute inflammatory reaction and hemodynamic changes of acute pulmonary embolism rabbit with hyperhomocysteinemia. METHODS: A total of 30 Japanese white rabbits were randomly divided into homocysteine group and control group according to the random number table, which were treated with 2% methionine and normal saline, respectively. Rabbit model of acute pulmonary embolism was established by autologous blood clots reinfusion after 8 weeks, then the level of serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), right ventricular systolic pressure (RVSP), right atria systolic pressure (RASP), pulmonary artery pressure (PAP) were checked before and after thrombosis at different time points. At last, area of embolism, degree of lung congestion and incidence of lung infarction were evaluated after the rabbits were sacrificed. RESULTS: Both homocysteine group and control group serum TNF-alpha, IL-1beta increased at 30, 60, 120 min after embolism, and serum TNF-alpha, IL-1beta of homocysteine group [(12.4 +/- 1.0), (15.7 +/- 1.1), (23.2 +/- 1.4) and (7.6 +/- 1.0), (10.2 +/- 2.1), (18.8 +/- 1.3) pg/ml] increased more obviously than control group [(10.2 +/- 1.0), (11.7 +/- 1.4), (12.1 +/- 1 .2) and (6.4 +/- 1.1), (8.5 +/- 1.9), (10.0 +/- 2.1) pg/ml] (all P<0.05). All of RVSP, RASP, and PAP increased in each group after embolism, while homocysteine group RVSP [(52.8 +/- 3.3), (54.7 +/- 4.5), (46.4 +/- 4.4) mmHg], RASP [(3.9 +/- 1.2), (4.5 +/- 2.0), (4.5 +/- 1.9) mmHg] and PAP[(52.9 +/- 3.3), (55.1 +/- 2.9), (47.5 +/- 3.6) mmHg] increased more obviously compared with control group [(39.4 +/- 2.5), (39.4 +/- 3.3), (34.5 +/- 3.9) mmHg, (2.3 +/- 1.1), (3.3 +/- 1.1), (3.3 +/- 1.2) mmHg and (37.7 +/- 2.7), (40.2 +/- 2.9), (33.7 +/- 4.2) mmHg] (all P<0.05). CONCLUSION: Inflammatory response of acute pulmonary embolism rabbit increases in hyperhomocysteinemia and the degree of embolism increases as well, which may lead to increase of hemodynamic instability. PMID- 26850018 TI - [Expression of the pulmonary surfactant in rat with paraquat-induced acute lung injury]. AB - OBJECTIVE: To explore the expression of pulmonary surfactant in rats with paraquat-induced acute lung injury. METHODS: A total of 36 SD rats were randomly divided into the control group (n=6) and paraquat group at 6, 12, 24, 48, 72 h five time points, each time points 6 rats. All of the rats were injected with paraquat (80 mg/kg) for once. The specimens were collected at 0 h (instant) after paraquat intoxication in the control group, and at the corresponding point in time in the paraquat each time point groups. The pathology changes of lung tissue were observed by HE staining, thiobarbituric acid method was used to detect malondialdehyde (MDA) level, and Western blot method was used to analyze the relative expression of surfactant protein (SP)-A and SP-D in bronchoalveolar lavage fluid (BALF) with time. RESULTS: As compared to control, the levels of MDA in BALF were significantly higher at 6, 24, 48 h after paraquat intoxication ((4.19 +/- 0.12), (3.33 +/- 0.08), (3.52 +/- 0.08) vs (2.82 +/- 0.15) nmol/mg, all P<0.01), no significantly different at 12, 72 h ((2.76 +/- 0.13), (2.79 +/- 0.10) nmol/mg, both P>0.05); the relative expression of SP-A in BALF were significantly higher at 6 h after paraquat intoxication (1.32 +/- 0.19 vs 1.00 +/ 0.19, P<0.01), lower at 24, 48 h (0.43 +/- 0.07, 0.67 +/- 0.08, both P<0.01), and no significantly different at 12, 72 h (0.98 +/- 0.15, 0.79 +/- 0.18, both P>0.05); the relative expression of SP-D in BALF were significantly higher at 6, 12 h after paraquat intoxication (1.54 +/- 0.33, 1.64 +/- 0.37 vs 1.00 +/- 0.23, both P<0.01), no significantly different at 24, 48 h (1.07 +/- 0.19, 0.97 +/- 0.15, both P>0.05), and reached the peak at 72 h (2.15 +/- 0.26, P<0.01); the expression of MDA, SP-A and SP-D were characterized by the state of fluctuation with increased first, reduced after, and finally increased. CONCLUSION: The expression of SP-A, SP-D increase at the early stage of the paraquat-induced acute lung injury in rat, which can reflect the degree of lung injury. PMID- 26850019 TI - [Expressions of Notch3, Notch4, Frizzled2 and Tead1 in rats with focal cerebral ischemia-reperfusion]. AB - OBJECTIVE: To investigate the expressions of Notch3, Notch4, Frizzled2 and Tead1 at protein levels in the cortex of frontal and parietal lobes after focal cerebral ischemia-reperfusion (I/R) in rats. METHODS: The focal cerebral I/R model was established by intraluminal thread occlusion of the middle cerebral artery (MCAO). The animals were divided into sham operation group (sham group) and I/R group. The infarct area of the brain was measured by 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining technique after 1 week. Protein expression levels of Notch3 and Frizzled2 in the cortex of frontal and parietal lobes were detected by immunohistochemical staining, and protein expression levels of Notch4 and Tead1 were detected by Western blot analysis. RESULTS: The infarct area of rats in I/R group was very obvious. The protein expressions of Notch3 and Frizzled2 in I/R group were higher than those in sham group (P<0.05, P<0.01). The protein expression of Notch4 in I/R group was significantly higher than that in sham group (P<0.01), but the protein expression level of Tead1 in I/R group was significantly lower than that in sham group(P<0.01). CONCLUSION: Notch signal transduction pathway was activated after focal cerebral ischemia/reperfusion in MCAO rats. PMID- 26850020 TI - [Effects of thyroid autoimmunity on pregnancy outcomes in euthyroid women receiving in vitro fertilization: a meta-analysis]. AB - OBJECTIVE: To investigate the association of thyroid autoimmunity (TAI) with pregnancy outcomes in euthyroid women undergoing in vitro fertilization (IVF). METHODS: The meta-analysis was a systematic review of cohort studies published before May 10th, 2014. Data were retrieved from Medline, Embase and Cochrane library, and the keywords were "thyroid autoimmunity" and "pregnancy outcome", with restriction to artificial reproductive technique. RevMan 5.2 software was used for data analysis. RESULTS: In all, 11 cohort studies met the inclusion criteria and were included in the meta-analysis. The results showed that TAI was not associated with clinical pregnancy rate (RR=0.99, 95%CI: 0.89-1.11, P=0.92), but significantly associated with miscarriage risk (RR=1.54, 95%CI: 1.24-1.92, P<0.001). Live birth/ongoing pregnancy rate decreased in the TAI group compared with the control group, but there was no statistically significant difference (RR=0.89, 95%CI: 0.79-1.00, P=0.06). CONCLUSION: As for euthyroid women who are receiving IVF, TAI contributes to increased risk of miscarriage. Therefore, we recommend universal screening for thyroid disease among women undergoing IVF. PMID- 26850021 TI - [Study on the feasibility of human papilloma virus subtypes detection by automatic nucleic acid extraction workstation]. AB - OBJECTIVE: To verify the feasibility of human papilloma virus(HPV) subtypes detection by AUTRAX automatic nucleic acid extraction workstation. METHODS: A total of 183 HPV test samples (2 562 types) were collected during August 2014 in Peking Union Medical College Hospital. Nucleic acid determination kit of high risk HPV types (16, 18, 35, 39, 58, 31, 33, 68, 56, 45, 59, 51, 52) and 6 , 11 type (real-time PCR) were applied for detection. Each sample was divided into two parts. One part was treated with manual extraction, which entailed manually preparing PCR reaction system and added the sample to the PCR plate. Another was treated with the AUTRAX automatic nucleic acid extraction workstation, which automatically prepared the reaction system and added to the PCR board. These two parts proceeded to the real-time PCR detection. The result of manual extraction was set as the golden standard and the Kappa consistency analysis was conducted. Meanwhile, precision and pollution prevention of the AUTRAX were verified. RESULTS: The sensitivity of AUTRAX automatic nucleic acids extraction workstation was 97.12% (101/104). The specificity was 99.51% (2 446/2 458). The accuracy was 99.42% (2 547/2 562). The result of Kappa consistency analysis showed that the two parts were the same (Kappa=0.926). Coefficient of variation (CV) of each HPV types was less than 5%.No pollution phenomenon was found. CONCLUSION: AUTRAX automatic nucleic acids extraction workstation can be used for the HPV subtypes detection in clinical settings. PMID- 26850022 TI - Identification of Dominant Excitation Patterns and Sources of Atrial Fibrillation by Causality Analysis. AB - Burden of atrial fibrillation (AF) can be reduced by ablation of sources of electrical impulses driving AF but driver identification is still challenging. This study presents a new methodology based on causality analysis that allows identifying the hierarchically dominant areas driving AF. Identification of dominant propagation patterns was achieved by computing causal relations between intracardiac multi-electrode catheter recordings of four paroxysmal AF patients during sinus rhythm, pacing and AF. In addition, realistic mathematical models of the atria during AF were used to validate the methodology both in the presence and absence of dominant frequency (DF) gradients. During electrical pacing, sources of propagation patterns detected by causality analysis were consistent with the location of the stimulating catheter. During AF, propagation patterns presented temporal variability, but a dominant direction accounted for significantly more propagations than other directions (49 +/- 15% vs. 14 +/- 13% or less, p < 0.01). Both in patients with a DF gradient and in mathematical models, causal maps allowed the identification of sites responsible for maintenance of AF. Causal maps allowed the identification of atrial dominant sites. In particular, causality analysis resulted in stable dominant cause-effect propagation directions during AF and could serve as a guide for performing ablation procedures in AF patients. PMID- 26850023 TI - Better quality of life in patients offered financial incentives for taking anti psychotic medication: Linked to improved adherence or more money? AB - PURPOSE: In a randomised controlled trial, patients were offered financial incentives to improve their adherence to anti-psychotic maintenance medication. Compared to a control group without the incentives, they had an improved adherence and also better subjective quality of life (SQOL) after 1 year. This paper explores the question as to whether this improvement in SQOL was associated with the amount of money received or with the improved adherence itself. METHOD: A secondary analysis was performed using data of the experimental group in the trial. Adherence was assessed as the percentage of all prescribed long-acting anti-psychotic injections that were taken by the patient. In regression models, we tested whether changes in medication adherence and/or the amount of incentives received over the 12-month period was associated with SQOL, as rated on the DIALOG scale. RESULTS: Adherence changed from 68.49 % at baseline to 88.23 % (mean difference in adherence = 19.59 %, SD = 17.52 %). The total amount of incentives received within the 1-year study period varied between L75 and L735, depending on the treatment cycle and the number of long-acting injections taken. Improvement in adherence was found to be a significant predictor of better subjective quality of life (beta = 0.014, 95 % CI 0.003-0.025, p = 0.014), whilst the amount of incentives received was not (beta = 0.0002, 95 % CI -0.002 to 0.002, p = 0.818). CONCLUSION: Improved medication adherence is associated with a more favourable SQOL. This underlines the clinical relevance of improved adherence in response to financial incentives in this patient group. PMID- 26850025 TI - Adapting the robotic platform to small operating theaters: our experience with the side-docking technique for robotic-assisted laparoscopic prostatectomy. AB - INTRODUCTION: Conventionally, in robotic-assisted laparoscopic prostatectomy (RALP), the robot is entered between the abducted legs of the patient. This approach may present drawbacks, including the limited access to the perineum, the inevitable abduction of the patient's legs, and the limited space available in small operating theaters. To overcome these problems, in our center, we use, from over 5 years, a side-docking technique. We herein describe our technique and a series of patients who underwent RALP using such side-docking procedure. METHODS: In our department, we have applied the side-docking technique for over 5 years, mainly in RALP procedures. The series reported includes 268 men undergoing RALP +/- extended lymph node dissection (ePLND) between mid-2010 and 2014. After trocart positioning, the robot is entered at a 45 degrees angle compared to the patient's main axis, coming in from the right side. Patient's legs are minimally abducted to <10 degrees . RESULTS: Mean docking time, from skin incision to full docking was 13 min. 41 % (109/268) of patients underwent simultaneous ePLND, dissecting nodes up till at least the iliac bifurcation. No conversion to open surgery was required. External collisions are infrequent with this configuration: No re-docking was necessary in this cohort. CONCLUSIONS: Side-docking of the da Vinci robot is a safe alternative for RALP. In our department, this technique has faced the proof of time and is routinely used. PMID- 26850024 TI - Can biological motion research provide insight on how to reduce friendly fire incidents? AB - The ability to accurately detect, perceive, and recognize biological motion can be associated with a fundamental drive for survival, and it is a significant interest for perception researchers. This field examines various perceptual features of motion and has been assessed and applied in several real-world contexts (e.g., biometric, sport). Unexplored applications still exist however, including the military issue of friendly fire. There are many causes and processes leading to friendly fire and specific challenges that are associated with visual information extraction during engagement, such as brief glimpses, low acuity, camouflage, and uniform deception. Furthermore, visual information must often be processed under highly stressful (potentially threatening), time constrained conditions that present a significant problem for soldiers. Biological motion research and anecdotal evidence from experienced combatants suggests that intentions, emotions, identities of human motion can be identified and discriminated, even when visual display is degraded or limited. Furthermore, research suggests that perceptual discriminatory capability of movement under visually constrained conditions is trainable. Therefore, given the limited military research linked to biological motion and friendly fire, an opportunity for cross-disciplinary investigations exists. The focus of this paper is twofold: first, to provide evidence for the possible link between biological motion factors and friendly fire, and second, to propose conceptual and methodological considerations and recommendations for perceptual-cognitive training within current military programs. PMID- 26850026 TI - Long-term prognosis after endoscopic submucosal dissection for early gastric cancer in super-elderly patients. AB - BACKGROUND: No previous study has confirmed the safety of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in the super-elderly patient population. The current study aimed to evaluate the validity of ESD for EGC in super-elderly patients aged >=85 years with comorbidities. METHODS: Our study group included 85 super-elderly patients (102 EGCs) who were diagnosed at Hiroshima University Hospital between April 2002 and October 2014. We evaluated the en bloc resection rates, R0 resection rates, complication rates, and prognosis in relation to the degree of comorbidities (group A-H, patients with high-risk comorbidities; group A-L, patients with low-risk comorbidities; group B, patients without comorbidities; and group C, patients followed without ESD). RESULTS: The en bloc resection rates were 100, 96, and 100 % in groups A-H, A-L, and B, respectively. R0 resection rates were 94, 96, and 94 % in groups A-H, A-L, and B, respectively. There were no severe complications related to ESD. During the follow-up period, there was a significantly higher frequency of death in group A than in group B (p < 0.01), and there were no significant differences between groups A-H and A-L. However, there were no cases of death related to gastric cancer. CONCLUSIONS: ESD was performed safely, and death related to gastric cancer was prevented in super-elderly patients with comorbidities, regardless of the degree of the disease. However, patients with comorbidities are at a high risk of poor prognosis. PMID- 26850028 TI - [Not Available]. PMID- 26850027 TI - Three-dimensional reconstruction of the vascular arrangement including the inferior mesenteric artery and left colic artery in laparoscope-assisted colorectal surgery. AB - BACKGROUND: We performed three-dimensional (3D) reconstruction to investigate the vascular anatomy, including the inferior mesenteric artery (IMA), left colic artery (LCA), and inferior mesenteric vein (IMV), for laparoscope-assisted left side colorectal surgery. Furthermore, we also examined the distances from the root of the IMA to the bifurcation of the LCA and to the IMV using 3D imaging. METHODS: We retrospectively analyzed 46 patients who underwent laparoscope assisted left-side colorectal surgery via 3D surgical reconstruction at Tsukuba Medical Center Hospital. The branching patterns among the IMA, LCA, and sigmoidal colic artery (SCA) in colon cancer could be classified into three groups (types A, B, and C): type A, in which both arteries (LCA and SCA) branch off from the same point of the IMA; type B, in which the common trunk of the LCA and SCA branches off from the IMA; and type C, in which the LCA and SCA branch off separately from the IMA. The shortest length from the root of the IMA to bifurcation of the LCA and SCA branches (D mm) or to the IMV (d mm) was measured by 3D imaging. RESULTS: The mean D mm and d mm for all cases were 39.4 +/- 11.2 and 27.9 +/- 9.21 mm, respectively. The D mm from the IMA root to the LCA or SCA branch in types A, B, and C was 37.8 +/- 9.21, 40.5 +/- 12.7, and 38.6 +/- 10.2 mm, respectively. Similarly, the d mm from the IMA root to the IMV in types A, B, and C was 30.2 +/- 11.3, 29.9 +/- 7.27, and 25.2 +/- 10.3 mm, respectively. CONCLUSION: The present 3D reconstruction technique was useful for determining the 3D vascular anatomical pattern including the relative positions of the IMA, SCA, and IMV during laparoscope-assisted left-side colorectal surgery. PMID- 26850030 TI - What is this image? 2016-Image 1. PMID- 26850031 TI - Visual identification of coronary calcifications on attenuation correction CT improves diagnostic accuracy of SPECT/CT myocardial perfusion imaging. AB - BACKGROUND: Coronary artery calcium (CAC) is a powerful CAD risk marker when assessed by dedicated calcium scoring CT scan. We assessed diagnostic implications of CAC visible on attenuation correction CT scans (CTAC) from SPECT/CT myocardial perfusion imaging (MPI). METHODS: Visual presence or absence of CAC was assessed on CTAC in 1047 consecutive patients undergoing SPECT/CT MPI. Accuracy of MPI was assessed in patients undergoing invasive coronary angiography (ICA) within 1 year (n = 109). Outcomes were identified by retrospective chart review. RESULTS: Prevalence of true positive SPECT/CT MPI studies was greater among patients with CAC on CTAC (70% vs 16%; p < .001); prevalence of false positive studies was greater among those without (68% vs 15%; p < .001). PPV of MPI was 0.82 in patients with CAC, but only 0.19 in those without. Within median follow-up of 27.7 months, patients with CAC had higher all-cause mortality (6% vs 0.4%; p < .001), more late revascularizations (8% vs 0.4%; p < .001), and more MI (5% vs 0.2%; p < .001). Hazard ratio for all-cause mortality, MI, or late revascularization was 22.7 (p < .001) for patients with CAC vs those without. CONCLUSIONS: Visual assessment of CAC on CTAC should be performed during SPECT/CT MPI because it affects diagnostic certainty and may improve risk stratification. PMID- 26850032 TI - Sole Dependence on Urine Testing Strips and the Ability to Identify Clinically Significant Disease: Challenging the Current Paradigm for Heme Detection in General Clinical Situations. AB - BACKGROUND: The ability of health care professionals to provide patient care is potentially compromised when predicated on untested, although longstanding, perspectives. One such example is urinalysis testing, which has been currently simplified to use only urine testing strips for detection of microscopic hematuria. OBJECTIVE: To determine whether urine testing strips are sufficient for identification of clinically significant findings in urinalysis. METHODS: To determine the presence of microscopic hematuria, I examined a collection of urine specimens that had tested heme negative during the 3-month study period. RESULTS: Of the 342 patients from whom urine specimens were examined during this interval, 50 had microscopic hematuria, despite having tested negative for heme via urine testing strip. Also, 30% were not receiving any medication known to produce microscopic hematuria, and 18% had clinically significant pathology. CONCLUSIONS: Diagnosis of significant clinical pathologic manifestations would have been compromised had microscopic examination not been performed on the urine specimens from the cohort individuals. Examination of the novel approach of including microscopic examination of specimens in a specific clinical situation challenges the dominant paradigm of reliance on assaying using urine testing strips only, revealing that the current method is not only unreliable for determining microscopic hematuria but also is less than optimal in general clinical practice. The findings of this study provide evidence of the importance of microscopic evaluation as a routine component of urinalysis. PMID- 26850033 TI - The Constitution of the Human Embryo as Substantial Change. AB - This paper analyzes the transformation from the human zygote to the implanted embryo under the prism of substantial change. After a brief introduction, it vindicates the Aristotelian ideas of substance and accident, and those of substantial and accidental change. It then claims that the transformation from the multicelled zygote to the implanted embryo amounts to a substantial change. Pushing further, it contends that this substantial change cannot be explained following patterns of genetic reductionism, emergence, and self-organization, and proposes Gustavo Bueno's idea of anamorphosis as a means to encapsulate criticism against such positions. PMID- 26850035 TI - Longer shifts don't increase harm to patients, finds controversial study. PMID- 26850034 TI - Natural Parasitism in Fruit Fly (Diptera: Tephritidae) Populations in Disturbed Areas Adjacent to Commercial Mango Orchards in Chiapas and Veracruz, Mexico. AB - To determine the natural parasitism in fruit fly populations in disturbed areas adjacent to commercial mango orchards in the states of Chiapas and Veracruz, Mexico, we recorded over one year the fruit fly-host associations, fly infestation, and parasitism rates in backyard orchards and patches of native vegetation. We also investigated the relationship between fruit size, level of larval infestation, and percent of parasitism, and attempted to determine the presence of superparasitism. The most recurrent species in trap catches was Anastrepha obliqua (Macquart), followed by Anastrepha ludens (Loew), in both study zones. The fruit infestation rates were higher in Chiapas than in Veracruz, with A. obliqua again being the most conspicuous species emerging from collected fruits. The diversity of parasitoids species attacking fruit fly larvae was greater in Chiapas, with a predominance of Doryctobracon areolatus (Szepligeti) in both sites, although the exotic Diachasmimorpha longicaudata (Ashmead) was well established in Chiapas. Fruit size was positively correlated with the number of larvae per fruit, but this relationship was not observed in the level of parasitism. The number of oviposition scars was not related to the number of immature parasitoids inside the pupa of D. areolatus emerging from plum fruits. Mass releases of Di. longicaudata seem not to affect the presence or prevalence of the native species. Our findings open new research scenarios on the role and impact of native parasitoid species attacking Anastrepha flies that can contribute to the development of sound strategies for using these species in projects for augmentative biological control. PMID- 26850036 TI - MPs find no evidence that Cancer Drugs Fund was spent wisely. PMID- 26850037 TI - Accuracy of Intravenous Electrocardiography Confirmation of Peripherally Inserted Central Catheter for Parenteral Nutrition. AB - BACKGROUND: Parenteral nutrition (PN) is a life-saving therapy for patients with intestinal failure. Safe delivery of hyperosmotic solution requires a central venous catheter (CVC) with tip in the lower superior vena cava (SVC) or at the SVC-right atrium (RA) junction. To reduce cost and delay in use of CVC, new techniques such as intravascular electrocardiogram (ECG) are being used for tip confirmation in place of chest x-ray (CXR). The present study assessed for accuracy of ECG confirmation in home PN (HPN). METHODS: Records for all patients consulted for HPN from December 17, 2014, to June 16, 2015, were reviewed for patient demographics, diagnosis leading to HPN initiation, and ECG and CXR confirmation. CXRs were subsequently reviewed by a radiologist to reassess location of the CVC tip and identify those that should be adjusted. RESULTS: Seventy-three patients were eligible, and after assessment for research authorization and postplacement CXR, 17 patients (30% male) with an age of 54 +/- 14 years were reviewed. In all patients, postplacement intravascular ECG reading stated tip in the SVC. However, based on CXR, the location of the catheter tip was satisfactory (low SVC or SVC-RA junction) in 10 of 17 patients (59%). CONCLUSION: Due to the high osmolality of PN, CVC tip location is of paramount importance. After radiology review of CXR, we noted that 7 of 17 (41%) peripherally inserted central catheter lines were in an unsatisfactory position despite ECG confirmation. With current data available, intravenous ECG confirmation should not be used as the sole source of tip confirmation in patients receiving HPN. PMID- 26850038 TI - Mutations of pvdhfr and pvdhps genes in vivax endemic-malaria areas in Kota Marudu and Kalabakan, Sabah. AB - BACKGROUND: Malaria cases persist in some remote areas in Sabah and Sarawak despite the ongoing and largely successful malaria control programme conducted by the Vector Borne Disease Control Programme, Ministry Of Health, Malaysia. Point mutations in the genes that encode the two enzymes involved in the folate biosynthesis pathway, dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) enzymes confer resistance to pyrimethamine and sulfadoxine respectively, in both Plasmodium falciparum and P. vivax. The aim of the current study was to determine the mutation on both pvdhfr at codon 13, 33, 57, 58, 61, 117, and 173 and pvdhps genes at codon 383 and 553, which are potentially associated with resistance to pyrimethamine and sulfadoxine in P. vivax samples in Sabah. METHODS: Every individual was screened for presence of malaria infection using a commercial rapid dipstick assay, ParaMax-3TM (Zephyr Biomedical, India). Individuals tested positive for P. vivax had blood collected and parasite DNA extracted. The pvdhfr and pvdhps genes were amplified by nested-PCR. Restriction fragment length polymorphism (RFLP) was carried out for detection of specific mutations in pvdhfr at codons 13Leu, 33Leu, 57Ile/Leu, 58Arg, 61Met, 117Asn/Thr, and 173Leu and pvdhps at codons 383Gly and 553Gly. The PCR-RFLP products were analysed using the Agilent 2100 Bioanalyzer (Agilent Technology, AS). RESULTS: A total of 619 and 2119 individuals from Kalabakan and Kota Marudu, respectively participated in the study. In Kalabakan and Kota Marudu, 9.37 and 2.45 % were tested positive for malaria and the positivity for P. vivax infection was 4.2 and 0.52 %, respectively. No mutation was observed at codon 13, 33 and 173 on pvdhfr and at codon 553 on pvdhps gene on samples from Kalabakan and Kota Marudu. One hundred per cent mutations on pvdhfr were at 57Leu and 117Thr. Mutation at 58Arg and 61Met was observed to be higher in Kota Marudu 72.73 %. Mutation at 383Gly on pvdhps was highest in Kalabakan with 80.77 %. There are four distinct haplotypes of pvdhfr/pvdhps combination. CONCLUSIONS: The presence of triple and quintuple mutation combination suggest that the P. vivax isolates exhibit a high degree of resistant to sulfadoxine, pyrimethamine and sulfadoxine-pyrimethamine combination therapy. PMID- 26850041 TI - Subchronic exposure to static magnetic field differently affects zinc and copper content in murine organs. AB - PURPOSE: Static magnetic fields (SMF) have been widely used in research, medicine and industry. Since zinc and copper play an important role in biological systems, we studied the effects of the subchronic continuous SMF exposure on their distribution in murine tissues. MATERIALS AND METHODS: For 30 days, mice were exposed to inhomogeneous, vertical, downward or upward oriented SMF of 1 mT averaged intensity with spatial gradient in vertical direction. RESULTS: SMF decreased the amount of copper and zinc in liver. In brain, zinc levels were increased and copper levels were decreased. In spleen, zinc content was reduced, while copper amount remained unchanged. CONCLUSIONS: Subchronic exposure to SMF differently affected copper and zinc content in examined organs, and the changes were more pronounced for the downward oriented field. The outcome could be attributed to the protective, rather than the harmful effect of SMF. PMID- 26850042 TI - Endometrial gene expression in high- and low-fertility heifers in the late luteal phase of the estrous cycle and a comparison with midluteal gene expression. AB - Embryonic mortality is a major constraint to improving reproductive efficiency and profitability in livestock enterprises. We previously reported differential expression of genes with identified roles in cellular growth and proliferation, lipid metabolism, endometrial remodeling, inflammation, angiogenesis, and metabolic exchange in endometrial tissue on day 7 of the estrous cycle (D7), between heifers ranked as either high (HF) or low (LF) for fertility. The aim of the current study was to further elucidate the underlying molecular mechanisms contributing to early embryo loss by examining differential endometrial gene expression in HF or LF heifers at a later stage of the estrous cycle;day 14(D14). A second objective was to compare these expression profiles with those from midluteal HF and LF endometrium. Using the same animal model as employed in the previous study, we slaughtered HF and LF animals on D14, harvested endometrial tissue, and carried out global gene expression analysis using the Affymetrix Bovine GeneChip. Microarray analysis detected 430 differentially expressed genes (DEG) between HF and LF animals. Ingenuity Pathway Analysis revealed enrichment for a host of biological pathways including lipid metabolism, molecular transport, immune response, cell morphology and development, and cell growth and proliferation. Important DEG includedALB, BMPR2, CCL28, COL4A3/4, FADS1, ITGA6, LDLR, PLCB3, PPARG, PTGS2, and SLC27A4 Furthermore, DEG expressed on both D7 and D14 included:PCCB,SLC25A24,DAP, and COL4A4 This study highlights some of the pathways and mechanisms underpinning late luteal bovine endometrial physiology and endometrial-related conception rate variance. PMID- 26850040 TI - Feasibility outcomes of a presurgical randomized controlled trial exploring the impact of caloric restriction and increased physical activity versus a wait-list control on tumor characteristics and circulating biomarkers in men electing prostatectomy for prostate cancer. AB - BACKGROUND: Obesity is associated with tumor aggressiveness and disease-specific mortality for more than 15 defined malignancies, including prostate cancer. Preclinical studies suggest that weight loss from caloric restriction and increased physical activity may suppress hormonal, energy-sensing, and inflammatory factors that drive neoplastic progression; however, exact mechanisms are yet to be determined, and experiments in humans are limited. METHODS: We conducted a randomized controlled trial among 40 overweight or obese, newly diagnosed prostate cancer patients who elected prostatectomy to explore feasibility of a presurgical weight loss intervention that promoted a weight loss of roughly one kg. week(-1) via caloric restriction and physical activity, as well as to assess effects on tumor biology and circulating biomarkers. Measures of feasibility (accrual, retention, adherence, and safety) were primary endpoints. Exploratory aims were directed at the intervention's effect on tumor proliferation (Ki-67) and other tumor markers (activated caspase-3, insulin and androgen receptors, VEGF, TNFbeta, NFkappaB, and 4E-BP1), circulating biomarkers (PSA, insulin, glucose, VEGF, TNFbeta, leptin, SHBG, and testosterone), lymphocytic gene expression of corresponding factors and cellular bioenergetics in neutrophils, and effects on the gut microbiome. Consenting patients were randomized in a 1:1 ratio to either: 1) weight loss via a healthful, guidelines based diet and exercise regimen; or 2) a wait-list control. While biological testing is currently ongoing, this paper details our methods and feasibility outcomes. RESULTS: The accrual target was met after screening 101 cases (enrollment rate: 39.6%). Other outcomes included a retention rate of 85%, excellent adherence (95%), and no serious reported adverse events. No significant differences by age, race, or weight status were noted between enrollees vs. non enrollees. The most common reasons for non-participation were "too busy" (30%), medical exclusions (21%), and "distance" (16%). CONCLUSIONS: Presurgical trials offer a means to study the impact of diet and exercise interventions directly on tumor tissue, and other host factors that are feasible and safe, though modifications are needed to conduct trials within an abbreviated period of time and via distance medicine-based approaches. Pre-surgical trials are critical to elucidate the impact of lifestyle interventions on specific mechanisms that mediate carcinogenesis and which can be used subsequently as therapeutic targets. TRIAL REGISTRATION: NCT01886677. PMID- 26850043 TI - MicroRNA expression profiling in skeletal muscle reveals different regulatory patterns in high and low responders to resistance training. AB - Large variability exists in muscle adaptive response to resistance exercise (RE) training between individuals. Recent studies have revealed a significant role for microRNAs (miRNAs) in skeletal muscle plasticity. In this study, we investigated how RE affects miRNA expression and whether the variability of muscle hypertrophy to RE training may be attributed to differential miRNA regulation in the skeletal muscle. To screen high and low responders to RE, we had 18 young men perform arm curl exercise training. After screening, all the men performed 12 wk of lower body RE training, but only the high or low responders participated in the acute RE test before training. Muscle biopsies were obtained from the vastus lateralis muscle at baseline, 3 h after acute RE, and after the training period. Total RNA was extracted from the skeletal muscle, and miRNA expression (800 miRNAs) was analyzed. RE training increased the cross-sectional area of the biceps brachii ( 1.7-26.1%), quadriceps (2.2-16.8%), and hamstrings (1.6-18.4%). Eighty-five and 102 miRNAs were differentially expressed after acute and chronic RE, respectively (P < 0.05). Seventeen miRNAs, especially 23b-3p, 26a-5p, 32-5p, 148b-3p, and 376a 3p, were differentially expressed at baseline, and 23 miRNAs, especially let-7a 5p, 95, 148a-3p, and 376a-3p, and 26 miRNAs, especially 30d-5p and 376a-3p, were differentially regulated after acute and chronic RE, respectively, in the skeletal muscle between high and low responders, indicating that the expression patterns of several miRNAs are altered by acute or chronic RE, and that miRNAs are involved in skeletal muscle adaptation to RE training. PMID- 26850044 TI - A Comparison of the Use and Quality of Antidiabetic Medication Regimens Between Non-Hispanic Black and White Adults With Uncontrolled Type 2 Diabetes in the US: NHANES 2003-2012. AB - PURPOSE: The purpose of this study was to determine the use of clinical guideline recommended antidiabetic therapies among whites and blacks with uncontrolled type 2 diabetes. METHODS: A secondary data analysis based on NHANES 2003-2012 cohort data including non-Hispanic black and white adults with uncontrolled (A1C >=6.5%) type 2 diabetes. RESULTS: Blacks were more likely to have the highest levels of A1C compared to whites (A1C >9% = 29.8% vs 16.2%). There was no statistical difference in the use of recommended regimens across racial group (blacks 60.5% vs whites 66.0%). Blacks and whites who were most uncontrolled were least likely to be on recommended regimens (A1C 6.5%-7.4%: 78.5%, A1C 7.5%-9%: 57.2%; and A1C >9%: 54.1%). This pattern was most pronounced among blacks compared to whites but was not statistically different. Use of recommended therapies decreased 29.0 percentage points for blacks and 20.1 percentage points among whites from an A1C level of 6.5% to 7.4% to >9%, respectively. The total proportion of blacks and whites on intensified non-insulin triple or insulin-based therapies were 38.9% and 41.8%, respectively. CONCLUSIONS: Even though blacks were more likely than whites to have the highest A1C, no significant differences were found in the use of clinical-guideline recommended regimens or other regimen use outcomes. Along with lifestyle modification, further intensification of antidiabetic regimens may help improve glycemic control and other disparities between blacks and whites. PMID- 26850045 TI - Educational Needs and Technological Preferences of Fathers of Youth With Type 1 Diabetes. AB - PURPOSE: The purpose of this study was to identify the educational needs and technological preferences of fathers of youth aged 6 to 17 years with type 1 diabetes (T1DM). METHODS: Participants completed 2 surveys and 1 in-person semistructured interview. Survey data were collected via Qualtrics; interviews were recorded and transcribed. The quantitative data were analyzed with SPSS 22. RESULTS: Thirty fathers/stepfathers of youth 6 to 17 years old with T1DM participated in the study. Participants reported high levels of unmet diabetes related educational needs, including needs in fundamental areas of diabetes management such as treatment of hyperglycemia, hypoglycemia, and calculating and adjusting insulin doses. A majority of participants identified educational needs in more nuanced aspects of diabetes management, indicating a need for more information about insulin pumps and continuous glucose monitors, managing diabetes at school, and finding help for diabetes challenges. All participants used smartphone technology, and most expressed interest in receiving diabetes education via mobile technology. CONCLUSIONS: The findings contribute to our understanding of the educational needs of fathers of children with T1DM and provide preliminary support for the acceptability of delivering diabetes education via mobile technology. The incorporation of patient and caregiver perspectives into the development of mHealth diabetes education applications may increase engagement and improve health outcomes. PMID- 26850046 TI - Nursing students' perceived stress and coping behaviors in clinical training in Saudi Arabia. AB - BACKGROUND: Clinical training has been recognized as a stressful experience for nursing students. AIMS: The aims of this study were to identify levels and types of stressors among nursing students during their clinical training and their coping behaviors. METHODS: Data were collected using a purposive sampling method from 100 nursing students using a self-reported questionnaire composed of Perceived Stress Scale and Coping Behavior Inventory. RESULTS: Results showed that "assignments and workload" as well as "teachers and nursing staff" were the highest sources of stress in clinical training. The most common coping behaviors used were "problem-solving" and "staying optimistic". There was a significant difference in perceived stress among students in regard to the way of choosing nursing. There were significant differences in coping behaviors in regard to the presence of relatives in nursing, living status and mothers' educational level. The predictors of perceived stress were self-choosing for nursing and the presence of relatives in nursing, while the predictors for coping behaviors were stress from peers and daily life as well as mothers' educational level. CONCLUSIONS: Nursing teachers and staff are encouraged to develop strategies that decrease level of stress and promote adaptive coping behaviors among nursing students during their clinical training. PMID- 26850048 TI - [Not Available]. PMID- 26850049 TI - [Analgesia and delirium management]. PMID- 26850047 TI - Ethnic and demographic incidence of amyotrophic lateral sclerosis (ALS) in Brazil: A population based study. AB - Our objectives were to examine demographic and ethnic factors associated with amyotrophic lateral sclerosis in Brazil. The method used was a retrospective study of death certificates performed in June 2015, identifying the incidence of amyotrophic lateral sclerosis over 10 years, from January 2004 to December 2013, related to gender, age and race. Results revealed 8942 death certificates with 8152 as the underlying cause and 790 as a secondary cause. The average age was 62.7 +/- 13.2 years, with a predominance of males (1.3:1). The adjusted mortality rate over 20 years was 0.61 to 0.89/100,000 person-years, and over 45 years was 1.77 to 2.3/100,000 person-years. There was a predominance of amyotrophic lateral sclerosis in Caucasians compared to the general population above 20 years (2010 Census), with an odds ratio (OR) of 2.92 (95% CI 2.78-3.07). The OR in blacks was 0.04 (95% CI: 0.03-0.04), in mestizos was 0.05 (0.04-0.07), and in Indians was 0.02 (0.01-0.04). The mean age was lower than in European populations (48.5 +/- 12.3 years) (p < 0.0001). In conclusion, the incidence of amyotrophic lateral sclerosis in Brazil is close to other Latin American populations, with a lower age at death and clear predominance in Caucasians. PMID- 26850051 TI - [Not Available]. PMID- 26850052 TI - Analysis of selected social determinants of health and their relationships with maternal health service coverage and child mortality in Vietnam. AB - INTRODUCTION: Achieving a fair and equitable distribution of health in the population while progressing toward universal health coverage (UHC) is a key focus of health policy in Vietnam. This paper describes health barriers experienced by women (and children by inference) in Vietnam, and measures how UHC, with reference to maternal health services and child mortality rates, is affected by selected social determinants of health (SDH), termed 'barriers'. METHODS: Our study uses a cross-sectional design with data from the 2011 Vietnam Multiple Indicator Cluster Survey. The study sample includes 11,663 women, aged 15-49 years. Weighted frequency statistics are cross-tabulated with socioeconomic characteristics of the population to describe the extent and distribution of health barriers experienced by disadvantaged women and children in Vietnam. A subset of women who had a live birth in the preceding two years (n=1,383) was studied to assess the impact of barriers to UHC and health. Six multiple logistic regressions were run using three dependent variables in the previous two years: 1) antenatal care, 2) skilled birth attendants, and 3) child death in the previous 15 years. Independent predictor variables were: 1) low education (incomplete secondary education), 2) lack of access to one of four basic amenities. In a second set of regressions, a constructed composite barrier index replaced these variables. Odds ratios (ORs) and 95% confidence intervals (95% CI) were used to report regression results. RESULTS: In Vietnam, about 54% of women aged 15-49 years in 2011, had low education or lacked access to one of four basic amenities. About 38% of poor rural women from ethnic minorities experienced both barriers, compared with less than 1% of rich urban women from the ethnic majority. Incomplete secondary education or lack of one of four basic amenities was a factor significantly associated with lower access to skilled birth attendants (OR=0.28, 95% CI: 0.14-0.55; OR=0.19, 95% CI: 0.05-0.80) and a higher risk of having had a child death in the previous two years (OR=1.71, 95% CI: 1.28 2.30; OR=1.59, 95% CI: 1.20-2.10). CONCLUSIONS: Our study shows the need for accelerating education and infrastructure investments for ethnic minority communities living in rural areas so as to be able to contribute to equity oriented progress toward UHC. PMID- 26850054 TI - Severity and outcomes according to stroke etiology in patients under 50 years of age with ischemic stroke. AB - To analyze the association of stroke etiological subtypes with severity and outcomes at 3 and 12 months in patients <=50 years. Observational study of patients admitted to a stroke unit (2007-2013). VARIABLES: demographic data, vascular risk factors, comorbidities, severity on admission (NIHSS), and good functional outcome (mRS <= 1) at 3 and 12 months. We used multivariate analyses to evaluate the influence of stroke etiology on severity and outcomes. We included 214 patients, 58.3 % men, mean age 41.4 years. General linear models showed all etiologies were more severe than lacunar strokes (P < 0.05). Atherothrombotic strokes showed greater severity than those of undetermined and uncommon etiology, whereas cardioembolic strokes were more severe than cryptogenic. Taking into account specific etiologies, atherothrombotic strokes (B = 5.860; 95 % CI 2.979-8.751), cervical artery dissection (CAD) [B = 7.485; 95 % confidence interval (CI) 4.734-10.237], and atrial fibrillation (AF) strokes (B = 5.773; 95 % CI 2.704-8.132) were more severe than other etiologies. Logistic regression models showed that strokes of uncommon etiology, especially those not related to CAD, had a lower probability of good outcome at 3 months [odds ratio (OR) = 0.197; CI 95 % 0.044-0.873], whereas atherothrombotic strokes were associated with this probability at 12 months (OR = 0.187; 95 % CI 0.037-0.951; P = 0.007). In patients <=50 years of age, strokes of atherothrombotic, cardioembolic (particularly those due to AF), and uncommon etiology had a greater severity than the rest. Furthermore, strokes of uncommon etiology, especially those different from CAD, decreased the probability of a good outcome at 3 months, as did atherothrombotic strokes at 1 year. PMID- 26850053 TI - Transcription factor KLF6 upregulates expression of metalloprotease MMP14 and subsequent release of soluble endoglin during vascular injury. AB - After endothelial injury, the transcription factor Kruppel-like factor 6 (KLF6) translocates into the cell nucleus to regulate a variety of target genes involved in angiogenesis, vascular repair and remodeling, including components of the membrane transforming growth factor beta (TGF-beta) receptor complex such as endoglin and activin receptor-like kinase 1. The membrane metalloproteinase 14 (MMP14 or MT1-MMP) targets endoglin to release soluble endoglin and is involved in vascular inflammation and endothelial tubulogenesis. However, little is known about the regulation of MMP14 expression during vascular wounding. In vitro denudation of monolayers of human endothelial cell monolayers leads to an increase in the KLF6 gene transcriptional rate, followed by an upregulation of MMP14 and release of soluble endoglin. Concomitant with this process, MMP14 co localizes with endoglin in the sprouting endothelial cells surrounding the wound border. MMP14 expression at mRNA and protein levels is increased by ectopic KLF6 and downregulated by KLF6 suppression in cultured endothelial cells. Moreover, after wire-induced endothelial denudation, Klf6 (+/-) mice show lower levels of MMP14 in their vasculature compared with their wild-type siblings. Ectopic cellular expression of KLF6 results in an increased transcription rate of MMP14, and chromatin immunoprecipitation assays show that KLF6 interacts with MMP14 promoter in ECs, this interaction being enhanced during wound healing. Furthermore, KLF6 markedly increases the transcriptional activity of different reporter constructs of MMP14 gene promoter. These results suggest that KLF6 regulates MMP14 transcription and is a critical player of the gene expression network triggered during endothelial repair. PMID- 26850055 TI - Encoding lexical tones in jTRACE: a simulation of monosyllabic spoken word recognition in Mandarin Chinese. AB - Despite its prevalence as one of the most highly influential models of spoken word recognition, the TRACE model has yet to be extended to consider tonal languages such as Mandarin Chinese. A key reason for this is that the model in its current state does not encode lexical tone. In this report, we present a modified version of the jTRACE model in which we borrowed on its existing architecture to code for Mandarin phonemes and tones. Units are coded in a way that is meant to capture the similarity in timing of access to vowel and tone information that has been observed in previous studies of Mandarin spoken word recognition. We validated the model by first simulating a recent experiment that had used the visual world paradigm to investigate how native Mandarin speakers process monosyllabic Mandarin words (Malins & Joanisse, 2010). We then subsequently simulated two psycholinguistic phenomena: (1) differences in the timing of resolution of tonal contrast pairs, and (2) the interaction between syllable frequency and tonal probability. In all cases, the model gave rise to results comparable to those of published data with human subjects, suggesting that it is a viable working model of spoken word recognition in Mandarin. It is our hope that this tool will be of use to practitioners studying the psycholinguistics of Mandarin Chinese and will help inspire similar models for other tonal languages, such as Cantonese and Thai. PMID- 26850056 TI - Norms of valence and arousal for 14,031 Spanish words. AB - Most current models of research on emotion recognize valence (how pleasant a stimulus is) and arousal (the level of activation or intensity that a stimulus elicits) as important components in the classification of affective experiences (Barrett, 1998; Kuppens, Tuerlinckx, Russell, & Barrett, 2012). Here we present a set of norms for valence and arousal for a very large set of Spanish words, including items from a variety of frequencies, semantic categories, and parts of speech, including a subset of conjugated verbs. In this regard, we found that there were significant but very small differences between the ratings for conjugations of the same verb, validating the practice of applying the ratings for infinitives to all derived forms of the verb. Our norms show a high degree of reliability and are strongly correlated with those of Redondo, Fraga, Padron, and Comesana's (2007) Spanish version of the influential Affective Norms for English Words (Bradley & Lang, 1999), as well as those from Warriner, Kuperman, and Brysbaert (2013), the largest available set of emotional norms for English words. Additionally, we included measures of word prevalence-that is, the percentage of participants that knew a particular word-for each variable (Keuleers, Stevens, Mandera, & Brysbaert, 2015). Our large set of norms in Spanish not only will facilitate the creation of stimuli and the analysis of texts in that language, but also will be useful for cross-language comparisons and research on emotional aspects of bilingualism. The norms can be downloaded and available as a supplementary materials to this article. PMID- 26850057 TI - Clinical characteristics and prevalence of complications of chronic kidney disease in children: the Taiwan Pediatric Renal Collaborative study. AB - BACKGROUND: Little information is available regarding the clinical characteristics and prevalence of complications in children with chronic kidney disease (CKD), especially in early disease stages. The objective of this study was to determine the clinical characteristics and prevalence of complications in children with predialytic CKD. METHODS: This multicenter, cross-sectional study enrolled children at all stages of predialytic CKD. Children who were between the ages of 1 year and 18 years and who fulfilled the clinical criteria of CKD were included in the study. Baseline demographic data, previous history, clinical characteristics, and laboratory data were collected. RESULTS: A total of 757 children were included in the study. The median age at the time of enrollment was 10.6 years; 397 patients (52.4 %) were males. A total of 39.0 % of the patients were in CKD stage 1, 37.6 % were in stage 2, 14.8 % were in stage 3, 3.0 % were in stage 4, and 5.5 % were in stage 5. Nonglomerular renal diseases were the primary cause of CKD, comprising 51.9 % of the patients with CKD. The age at disease onset, gender, CKD stage distribution, and proportion of co-morbidities varied between the glomerular and nonglomerular CKD cases. Anemia, hyperlipidemia, hypocalcemia, and hyperphosphatemia were more prevalent in patients with glomerular CKD. The overall prevalence of complications was as follows: uncontrolled blood pressure, 44.1 %; anemia, 34.2 %; hyperlipidemia, 44.9 %; short stature, 10.3 %; and failure to thrive, 8.2 %. Uncontrolled blood pressure (BP), anemia, and hyperlipidemia were common, even in the early CKD stages. The prevalence of CKD complications generally increased with the worsening stage of CKD. CONCLUSIONS: This study reveals differences in CKD etiology and prevalence of specific complications according to the stage of CKD. Early recognition and awareness of complications are mandatory for clinicians during the follow-up visits of children with CKD. PMID- 26850058 TI - Generation of a neutralization-resistant CCR5 tropic simian/human immunodeficiency virus (SHIV-MK38) molecular clone, a derivative of SHIV-89.6. AB - Previously, we reported that a new genetically diverse CCR5 (R5) tropic simian/human immunodeficiency virus (SHIV-MK38) adapted to rhesus monkeys became more neutralization resistant to SHIV-infected plasma than did the parental SHIV KS661 clone. Here, to clarify the significance of the neutralization-resistant phenotype of SHIV in a macaque model, we initially investigated the precise neutralization phenotype of the SHIVs, including SHIV-MK38 molecular clones, using SHIV-MK38-infected plasma, a pooled plasma of human immunodeficiency virus (HIV)-infected individuals, soluble CD4 and anti-HIV-1 neutralizing mAbs, the epitopes of which were known. The results show that SHIV-KS661 had tier 1 neutralization sensitivity, but monkey-adapted R5 tropic SHIV-MK38 acquired neutralization resistance similar to that of tier 2 or 3 as a clone virus. Sequence analysis of the env gene suggested that the neutralization-resistant phenotype of SHIV-MK38 was acquired by conformational changes in Env associated with the net charge and potential N-linked glycosylation sites. To examine the relationship between neutralization phenotype and stably persistent infection in monkeys, we performed in vivo rectal inoculation experiments using a SHIV-MK38 molecular clone. The results showed that one of three rhesus monkeys exhibited durable infection with a plasma viral load of 105 copies ml- 1 despite the high antibody responses that occurred in the host. Whilst further improvements are required in the development of a challenge virus, it will be useful to generate a neutralization-resistant R5 tropic molecular clone of the SHIV-89.6 lineage commonly used for vaccine development - a result that can be used to explore the foundation of AIDS pathogenesis. PMID- 26850059 TI - Challenges of early detection of oral cancer: raising awareness as a first step to successful campaigning. AB - In Germany, ~ 13,000 people are found to have oral and pharyngeal cancer every year. Awareness and knowledge about this cancer remain insufficient, particularly amongst elderly people. A campaign for early detection was launched in Northern Germany in April 2012. The first step of the campaign was to increase awareness about oral cancer. Prior to a pre-campaign evaluation at the campaign start, March 2012 and an intermediate-campaign evaluation, November 2012, a sample representative for the population aged 50 >= years (target group; N = 500) was drawn for a first process evaluation. The surveys were conducted by means of telephone interviews including questions on behaviour, knowledge and sociodemographic/socioeconomic aspects and target group-oriented questions on issue, media and campaign material awareness. The process evaluation showed an increase in issue awareness from 25 to 40% (P < 0.001) and the media awareness increased by over 10% (P < 0.001). The results suggested that particularly women, the core age group (60-79 years) and the educationally disadvantaged group might benefit from the campaign. Awareness about the issue 'oral cancer' was already significantly increased 7 months after the campaign start. The highest general and media-related increase in awareness was achieved in the target group. PMID- 26850061 TI - Texting your way to healthier eating? Effects of participating in a feedback intervention using text messaging on adolescents' fruit and vegetable intake. AB - This study investigates the effects of a feedback intervention employing text messaging during 11 weeks on adolescents' behavior, self-efficacy and outcome expectations regarding fruit and vegetable intake. A pre- and post-survey was completed by 1488 adolescents school-wise randomly allocated to a control group and two experimental groups. Both experimental groups set weekly goals on fruit and vegetable intake, reported their consumption daily and subsequently received feedback on their performance via mobile text messaging (Short Message Service [SMS]). The second experimental group also received, in addition, a 45-min nutrition education session from a dietitian during school. The direct effects of the interventions were not significant. However, for adolescents participating in the SMS routines, there were significant effects of the level of engagement in the intervention, reflected in the number of sent text messages, on intervention outcomes. Participants sending more than half of the possible text messages significantly increased their fruit and vegetable intake. Participants sending between 10% and 50% of the possible text messages experienced a significant drop in self-efficacy and those sending less than 10% experienced a significant drop in outcome expectations. The findings suggest that participants' active engagement in an intervention is crucial to its success. Implications for health promoting interventions are discussed. PMID- 26850062 TI - Controversies in the treatment of patients with STEMI and multivessel disease: is it time for PCI of all lesions? AB - Several randomized trials have suggested a benefit for multivessel PCI in patients with STEMI and multivessel disease. However, none of the studies compared multivessel PCI with a staged PCI-approach which is the current guideline recommended approach. The results of the trials may overestimate the beneficial effect of the multivessel PCI approach because the control group did not receive any ischaemia testing for evaluation of the significance of remaining lesions. Thus, unfavourable aspects of the multivessel PCI approach such as overestimation of non-culprit lesions at the time of acute coronary angiography, complications associated with PCI of the non-culprit lesion (i.e. dissection, no reflow, acute stent thrombosis) or increased risk for contrast induced nephropathy may have gone unnoticed as the comparative management pathway was unusual and likely inferior to the guideline recommended approach. We believe that culprit lesion only PCI and staged evaluation of remaining areas of myocardial ischaemia with subsequent PCI is still preferable in patients with STEMI and multivessel disease but a randomized study comparing this approach with multivessel PCI is needed. PMID- 26850060 TI - School district wellness policy quality and weight-related outcomes among high school students in Minnesota. AB - Weight-related outcomes were examined among high school students in Minnesota public school districts according to the quality of district wellness policies. Wellness policy strength and comprehensiveness were scored using the Wellness School Assessment Tool (WellSAT) for 325 Minnesota public school districts in 2013. The associations between WellSAT scores and district-level means of high school student responses to a statewide survey of health behaviors were examined in this ecologic study. WellSAT Total Strength and Total Comprehensiveness scores were positively associated with both student mean Body Mass Index (BMI) percentile (Strength: P = 0.018, Comprehensiveness: P = 0.031) and mean percent overweight or obese (Strength: P = 0.008, Comprehensiveness: P = 0.026), but only in districts with > 50% of students eligible for Free or Reduced-Price Lunches (FRPLs), or 'high FRPL districts'. WellSAT Physical Education and Physical Activity subscale scores were also positively associated with the mean days per week students engaged in physical activity for >= 60 min in high FRPL districts (Strength: P = 0.008, Comprehensiveness: P = 0.003) and in low FRPL districts (< 35% eligible) for Strength score: (P = 0.027). In medium FRPL districts (35-50% eligible), Nutrition Education and Wellness Promotion Strength and Comprehensiveness subscale scores were positively associated with, respectively, daily servings of vegetables (P = 0.037) and fruit (P = 0.027); and WellSAT Total scores were positively associated with daily vegetable servings (Strength: P = 0.037, Comprehensiveness: P = 0.012). Administrators of economically disadvantaged school districts with a higher percentage of overweight students may be recognizing the need for stronger wellness policies and the specific importance of implementing policies pertaining to physical activity as a means to improve student health. PMID- 26850063 TI - Medical cannabis: considerations for the anesthesiologist and pain physician. AB - PURPOSE: New regulations are in place at the federal and provincial levels in Canada regarding the way medical cannabis is to be controlled. We present them together with guidance for the safe use of medical cannabis and recent clinical trials on cannabis and pain. SOURCE: The new Canadian regulations on the use of medical cannabis, the provincial regulations, and the various cannabis products available from the Canadian Licensed Producers were reviewed from Health Canada, provincial licensing authorities, and the licensed producers website, respectively. Recent clinical trials on cannabis and pain were reviewed from the existing literature. PRINCIPAL FINDINGS: Health Canada has approved a new regulation on medical marijuana/cannabis, the Marihuana for Medical Purposes Regulations: The production of medical cannabis by individuals is illegal. Health Canada, however, has licensed authorized producers across the country, limiting the production to specific licenses of certain cannabis products. There are currently 26 authorized licensed producers from seven Canadian provinces offering more than 200 strains of marijuana. We provide guidance for the safe use of medical cannabis. The recent literature indicates that currently available cannabinoids are modestly effective analgesics that provide a safe, reasonable therapeutic option for managing chronic non-cancer-related pain. CONCLUSION: The science of medical cannabis and the need for education of healthcare professionals and patients require continued effort. Although cannabinoids work to decrease pain, there is still a need to confirm these beneficial effects clinically and to exploit them with acceptable benefit-to-risk ratios. PMID- 26850064 TI - Perioperative management and oncological outcomes following radical cystectomy for bladder cancer: a matched retrospective cohort study. AB - PURPOSE: The immune system plays an important role in tumour progression. Systemic opioids are immunosuppressive; thus, theoretically they may promote tumour spread. Our primary aim was to test the hypothesis that general anesthesia (GA) with spinal analgesia (SA) in patients with bladder cancer undergoing radical cystectomy (RC) will both reduce systemic opioid use and improve oncological outcomes. Since blood transfusions also induce immunosuppression, a secondary aim was to evaluate the effect of perioperative transfusions on oncological outcomes. METHODS: One hundred ninety-five patients who underwent RC with GA+SA from 1998-2007 were matched 1:1 to controls who underwent surgery with GA only using propensity scoring and tumour characteristics known to be highly associated with oncological outcomes. Medical records were reviewed for use of opioids and transfusions. Outcomes were tumour recurrence, cancer-specific mortality, and all-cause mortality. Survival was estimated using the Kaplan-Meier method, and associations of anesthetic technique and transfusions with outcomes were analyzed using stratified multivariable proportional hazard regression. RESULTS: Systemic opioid use was reduced with GA+SA relative to GA (P < 0.001). There was no difference between groups with respect to all-cause mortality (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.77 to 1.53; P = 0.636), bladder cancer mortality (HR, 1.03; 95% CI, 0.66 to 1.61; P = 0.893), or cancer recurrence (HR, 1.32; 95% CI, 0.86 to 2.02; P = 0.205). Nevertheless, patients who were perioperatively transfused had an increased all-cause mortality (HR, 2.21; 95% CI, 1.11 to 4.40; P = 0.025), and cancer-specific mortality (HR, 2.61; 95% CI, 1.05 to 6.48; P = 0.039). CONCLUSIONS: In patients undergoing RC, the opioid-sparing effect with SA was not associated with improved oncological outcomes, while blood transfusion was associated with increased mortality. PMID- 26850065 TI - Ataxin-2 (Atxn2)-Knock-Out Mice Show Branched Chain Amino Acids and Fatty Acids Pathway Alterations. AB - Human Ataxin-2 (ATXN2) gene locus variants have been associated with obesity, diabetes mellitus type 1,and hypertension in genome-wide association studies, whereas mouse studies showed the knock-out of Atxn2 to lead to obesity, insulin resistance, and dyslipidemia. Intriguingly, the deficiency of ATXN2 protein orthologs in yeast and flies rescues the neurodegeneration process triggered by TDP-43 and Ataxin-1 toxicity. To understand the molecular effects of ATXN2 deficiency by unbiased approaches, we quantified the global proteome and metabolome of Atxn2-knock-out mice with label-free mass spectrometry. In liver tissue, significant downregulations of the proteins ACADS, ALDH6A1, ALDH7A1, IVD, MCCC2, PCCA, OTC, together with bioinformatic enrichment of downregulated pathways for branched chain and other amino acid metabolism, fatty acids, and citric acid cycle were observed. Statistical trends in the cerebellar proteome and in the metabolomic profiles supported these findings. They are in good agreement with recent claims that PBP1, the yeast ortholog of ATXN2, sequestrates the nutrient sensor TORC1 in periods of cell stress. Overall, ATXN2 appears to modulate nutrition and metabolism, and its activity changes are determinants of growth excess or cell atrophy. PMID- 26850069 TI - What is the role of coronary angioplasty and stenting in stable angina? PMID- 26850066 TI - Acquired immune responses to three malaria vaccine candidates and their relationship to invasion inhibition in two populations naturally exposed to malaria. AB - BACKGROUND: Malaria still represents a major cause of morbidity and mortality predominantly in several developing countries, and remains a priority in many public health programmes. Despite the enormous gains made in control and prevention the development of an effective vaccine represents a persisting challenge. Although several parasite antigens including pre-erythrocytic antigens and blood stage antigens have been thoroughly investigated, the identification of solid immune correlates of protection against infection by Plasmodium falciparum or clinical malaria remains a major hurdle. In this study, an immuno epidemiological survey was carried out between two populations naturally exposed to P. falciparum malaria to determine the immune correlates of protection. METHODS: Plasma samples of immune adults from two countries (Ghana and Madagascar) were tested for their reactivity against the merozoite surface proteins MSP1-19, MSP3 and AMA1 by ELISA. The antigens had been selected on the basis of cumulative evidence of their role in anti-malarial immunity. Additionally, reactivity against crude P. falciparum lysate was investigated. Purified IgG from these samples were furthermore tested in an invasion inhibition assay for their antiparasitic activity. RESULTS: Significant intra- and inter- population variation of the reactivity of the samples to the tested antigens were found, as well as a significant positive correlation between MSP1-19 reactivity and invasion inhibition (p < 0.05). Interestingly, male donors showed a significantly higher antibody response to all tested antigens than their female counterparts. In vitro invasion inhibition assays comparing the purified antibodies from the donors from Ghana and Madagascar did not show any statistically significant difference. Although in vitro invasion inhibition increased with breadth of antibody response, the increase was not statistically significant. CONCLUSIONS: The findings support the fact that the development of semi-immunity to malaria is probably contingent on the development of antibodies to not only one, but a range of antigens and that invasion inhibition in immune adults may be a function of antibodies to various antigens. This supports strategies of vaccination including multicomponent vaccines as well as passive vaccination strategies with antibody cocktails. PMID- 26850070 TI - Former banker who hiked price of drug refuses to speak at congressional hearing. PMID- 26850068 TI - Metastatic EML4-ALK fusion detected by circulating DNA genotyping in an EGFR mutated NSCLC patient and successful management by adding ALK inhibitors: a case report. AB - BACKGROUND: Rebiopsy is highly recommended to identify the mechanism of acquired resistance to EGFR-TKIs in advanced lung cancer. Recent advances in multiplex genotyping based on circulating tumor DNA (ctDNA) provide a strong and non invasive alternative for detection of the resistance mechanism. CASE PRESENTATION: Here we report a multiple metastatic NSCLC patient who was detected to have pure EGFR 19 exon deletion (negative for EML4-ALK and ROS1 in both IHC based and sequencing assay) in the primary lesion and responded to first-line and second-line EGFR-TKI treatments (erlotinib then HY-15772). At 8 months, most lesions remained well controlled except for the liver metastases which presented dramatic progression. Considering the high risk of bleeding in rebiopsy of hepatic lesions, we conducted a multiplex genomic profiling with ctDNA. Results reported coexistence of EGFR mutation and EML4-ALK gene translocation in plasma which heavily indicated that ALK was the primary reason for progression of the liver lesions. This deduction was supported by the repeated response to ALK inhibitors (crizotinib then AP26113) of the hepatic metastases. CONCLUSIONS: This is the first report of the existence of ALK rearrangement in metastatic lesions in an EGFR mutated patient. It highlighted the feasibility and advantages of using ctDNA multiplex genotyping in identifying the heterogeneity across lesions and the resistance mechanism of targeted treatments. PMID- 26850071 TI - Fostering dignity in the care of nursing home residents through slow caring. AB - BACKGROUND: Physical impairment and dependency on others may be a threat to dignity. RESEARCH QUESTIONS: The purpose of this study was to explore dignity as a core concept in caring, and how healthcare personnel focus on and foster dignity in nursing home residents. RESEARCH DESIGN: This study has a hermeneutic design. Participants and research context: In all, 40 healthcare personnel from six nursing homes in Scandinavia participated in focus group interviews in this study. Ethical considerations: This study has been evaluated and approved by the Regional Ethical Committees and the Social Science Data Services in the respective Scandinavian countries. FINDINGS: Two main themes emerged: dignity as distinction (I), and dignity as influence and participation (II). DISCUSSION: A common understanding was that stress and business was a daily challenge. CONCLUSION: Therefore, and according to the health personnel, maintaining human dignity requires slow caring in nursing homes, as an essential approach. PMID- 26850072 TI - A Chemically Defined Medium-Based Strategy to Efficiently Generate Clinically Relevant Cord Blood Mesenchymal Stromal Colonies. AB - During the last decade it has been demonstrated that mesenchymal progenitors are present and can be isolated also from cord blood (CB). Recently, we managed to set up a standard protocol allowing the isolation of mesenchymal stromal cells (MSCs) with high proliferative potential and multiple differentiation capabilities, whereas the generation rate of MSC-initiating colonies could still be further improved. Herein, we strikingly succeeded in defining some simple and basic culture conditions based on the use of a chemically defined medium that increased the colony isolation efficiency up to almost 80% of processed CB units. Importantly, this result was achieved irrespective of CB unit white blood cell content and time elapsed from delivery, two limiting parameters involved with processing CB units. Thus, this high efficiency is guaranteed without strict selection of the starting material. In addition, since we are profoundly concerned about how different culture conditions can influence cell behavior, we devoted part of this study to in-depth characterization of the established CB-MSC populations to confirm their stemness features in this novel isolation and culture system. Therefore, an extended study of their immunophenotype, including classical pericytic markers, and a detailed molecular analysis addressing telomere length and also stemness-related microRNA contribution were performed. In summary, we propose a straightforward, extremely efficient, and reliable approach to isolate and expand thoroughly characterized CB-MSCs, even when poor quality CB units are the only available source, or there is no space for an isolation to fail. PMID- 26850073 TI - Luteal phase support after mild ovulation induction with intrauterine insemination: an on-going debate. AB - OBJECTIVE: To evaluate the effect of luteal phase support (LPS) using progesterone vaginal gel on pregnancy rate (PR) and live birth rate (LBR) during cycles in which controlled ovarian stimulation (COH) was performed using gonadotropins with intrauterine insemination (IUI) cycles in patients with unexplained infertility and polycystic ovarian syndrome. MATERIALS AND METHODS: From 2010 to 2015, all IUI cycles in which COH was performed using gonadotropins were evaluated retrospectively. LPS was not used until July 2013, after which vaginal progesterone gel was applied in the luteal phase of IUI cycles. Both groups of patients were evaluated in terms of the effect of LPS on PR and LBR. RESULTS: In total, 1578 IUI cycles were evaluated, of which 481 were LPS (+) and 1097 LPS (-). PR and LBR per cycle were 10.6% and 7.4%, respectively, in the LPS (+) group, and 11.6% and 7.7%, respectively, in the LPS (-) group (p = 0.31 and p = 0.25). PR and LBR per patient were 17% and 12%, respectively, in the LPS (+) group, and 17.4% and 12.3%, respectively, in the LPS (-) group (p = 0.48 and p = 0.82). CONCLUSIONS: We found no difference in PR and LBR per cycle and per patient according to the use of LPS in IUI cycles in which COH was performed using gonadotropins. Thus, routine use of LPS in gonadotropin-stimulated cycles requires further research involving larger numbers of patients. PMID- 26850074 TI - Healthcare resource utilization and work loss in dermatomyositis and polymyositis patients in a privately-insured US population. AB - Background Dermatomyositis and polymyositis (DM/PM) are inflammatory myopathies characterized by muscle inflammation/weakness. Patients with DM/PM have a reduced quality-of-life and are at an increased risk for several comorbidities. Studies have assessed the incidence and prevalence of DM/PM; however, no study has estimated the burden of the diseases in terms of both healthcare resource utilization (HCRU) and work loss incurred by patients. Objective To provide a comprehensive, current estimate of the annual HCRU and work loss in DM/PM patients in the US. Methods All patients (aged 18-64 years) with a first diagnosis of DM/PM between January 1, 1998 and March 31, 2014 ('index date') were selected from a de-identified privately-insured administrative claims database. DM/PM patients were required to have continuous health-plan enrollment 12 months prior to and following their index date. Propensity-score (1:1) matching of DM/PM patients with non-DM/PM controls was carried out based on a logistic regression of demographic characteristics, comorbidities, costs, and HCRU to control for these confounding factors. Burden of HCRU and work loss (disability days and medically-related absenteeism) were compared between the matched DM/PM and the non-DM/PM cohorts over the 12-month period after the index date ('outcome period'). Results Of the 2617 DM/PM patients that met sample selection criteria, 2587 (98.9%) were matched with a non-DM/PM control. During the outcome period, DM/PM patients had significantly increased HCRU across places of service, including 44% more inpatient admissions (3.6 vs 2.5, p < 0.001), increased visits with specialists such as rheumatologists, neurologists and physical therapists, and filled 4.7 more prescriptions (32.2 vs 27.5, p < 0.001) than matched control patients. The increased HCRU led to significantly more medically-related work loss among DM/PM patients than matched controls (p < 0.001). Conclusions DM/PM imposes a substantial increase in healthcare resource use and is associated with statistically significantly greater work loss in the first year following diagnosis. PMID- 26850075 TI - Do mental health clinicians elicit a history of previous trauma in female psychiatric inpatients? AB - BACKGROUND: A history of trauma is linked to the development of a wide range of mental health problems, and has long-lasting physiological and psychological consequences. The importance of clinicians directly questioning trauma history has been consistently emphasised in the literature. AIMS: To investigate whether a trauma history is obtained from female psychiatry inpatients during an inpatient admission. METHODS: The study was a retrospective file audit of 100 female patients admitted to the psychiatric ward of a major metropolitan Melbourne Hospital between December 2013 and November 2014. RESULTS: In the files of 51% of patients there was no mention of whether or not the patient had a trauma-abuse history. Eight percent of patients had documentation stating there was no trauma-abuse history. Forty-one percent of the patients had documented evidence of a trauma-abuse history, although only 3% of these patients had a specific description provided. The presence of current illicit drug use and the diagnosis of borderline personality disorder were the only variables associated with an increase in the likelihood of having a documented trauma-abuse history. CONCLUSION: There is a need for clinician retraining, a trauma-informed care model and the incorporation of mandatory inquiry in best practice guidelines to generate a shift in culture in the delivery of mental health care services. PMID- 26850076 TI - The modified stepwise ablation guided by low-dose ibutilide in chronic atrial fibrillation trial (The MAGIC-AF Study). AB - AIMS: Complex fractionated atrial electrograms (CFAE) are targeted during persistent atrial fibrillation (AF) ablation. However, many CFAE sites are non specific resulting in extensive ablation. Ibutilide has been shown to reduce left atrial surface area exhibiting CFAE. We hypothesized that ibutilide administration prior to CFAE ablation would identify sites critical for persistent AF maintenance allowing for improved procedural efficacy and long-term freedom from atrial arrhythmias. METHODS AND RESULTS: Two hundred patients undergoing a first-ever persistent AF catheter ablation procedure were randomly assigned to receive either 0.25 mg of intravenous ibutilide or saline placebo upon completion of pulmonary vein isolation. Complex fractionated atrial electrogram sites were then targeted with ablation. The primary efficacy endpoint was the 1-year single procedure freedom from atrial arrhythmia off anti arrhythmic drugs. Similar procedural characteristics (procedure, fluoroscopy, and ablation times) were observed with both strategies despite a greater reduction in left atrial surface area with CFAE sites (8 vs. 1%, P < 0.0001) and AF termination during CFAE ablation with ibutilide compared with placebo (75 vs. 57%, P = 0.007). The primary efficacy endpoint was achieved in 56% of patients receiving ibutilide and 49% receiving placebo (P = 0.35). No significant differences in peri-procedural complications were observed in both groups. CONCLUSION: Despite a reduction in CFAE area and greater AF termination during CFAE ablation, procedural characteristics and clinical outcomes were unchanged when CFAE ablation was guided by ibutilide administration. CLINICAL TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov number: NCT01014741. PMID- 26850078 TI - Exposure to a 50-Hz magnetic field induced mitochondrial permeability transition through the ROS/GSK-3beta signaling pathway. AB - PURPOSE: To investigate the biological effects of a 50-Hz magnetic field (MF) on mitochondrial permeability. MATERIALS AND METHODS: Human amniotic epithelial cells were exposed to MF (50 Hz, 0.4 mT) for different durations. Mitochondrial permeability, mitochondrial membrane potential (DeltaPsim), cytochrome c (Cyt-c) release and the related mechanisms were explored. RESULTS: Exposure to the MF at 0.4 mT for 60 min transiently induced mitochondrial permeability transition (MPT) and Cyt-c release, although there was no significant effect on mitochondrial membrane potential (DeltaPsim). Other than decreasing the total Bcl-2 associated X protein (Bax) level, MF exposure did not significantly affect the levels of Bax and B-cell lymphoma-2 (Bcl-2) in mitochondria. In addition, cells exposed to the MF showed increased intracellular reactive oxidative species (ROS) levels and glycogen synthase kinase-3beta (GSK-3beta) dephosphorylation at 9 serine residue (Ser(9)). Moreover, the MF-induced MPT was attenuated by ROS scavenger (N-acetyl L-cysteine, NAC) or GSK-3beta inhibitor, and NAC pretreatment prevented GSK-3beta dephosphorylation (Ser(9)) caused by MF exposure. CONCLUSION: MPT induced by MF exposure was mediated through the ROS/GSK-3beta signaling pathway. PMID- 26850079 TI - The role of a video-assisted thoracic approach for rib fixation. AB - PURPOSE: Rib fixation remains a contentious issue in the current practice of orthopaedic, trauma and thoracic surgeons. Whilst rib fractures are undoubtedly associated with high levels of morbidity and mortality, the optimal surgical approach has not yet been fully elucidated in prospective trials and the volume of procedures performed remains low. METHODS: We evaluated 21 consecutive patients who underwent surgical rib fixation either via a standard thoracotomy approach or following the introduction of a video-assisted technique with minimal thoracic incisions. RESULTS: The average age of patients undergoing rib fixation was 47 and the median length of post-operative stay was 4 days. More than 70 % of patients were found to have concurrent haemothoraces, and 19 % had significant injuries to underlying intra-thoracic structures requiring repair. One patient returned to theatre for persistent blood loss; however, there were no other immediate complications or mortalities. CONCLUSIONS: We discuss the involvement of thoracic surgeons, early assessment of the thoracic cavity with video assistance and optimal peri-operative management with particular reference to cases which demonstrate recent changes in our practice. PMID- 26850082 TI - The challenge of measuring IL-33 in serum using commercial ELISA: lessons from asthma. AB - BACKGROUND: Interleukin-33 (IL-33) has been subject of extensive study in the context of inflammatory disorders, particularly in asthma. Many human biological samples, including serum, have been used to determine the protein levels of IL 33, aiming to investigate its involvement in asthma. Reliable methods are required to study the association of IL-33 with disease, especially considering the complex nature of serum samples. OBJECTIVE: We evaluated four IL-33 ELISA kits, aiming to determine a robust and reproducible approach to quantifying IL-33 in human serum from asthma patients. METHODS: IL-33 levels were investigated in serum of well-defined asthma patients by the Quantikine, DuoSet (both R&D systems), ADI-900-201 (Enzo Life Sciences), and SKR038 (GenWay Biotech Inc San Diego USA) immunoassays, as well as spiking experiments were performed using recombinant IL-33 and its soluble receptor IL-1RL1-a. RESULTS: We show that 1) IL 33 is difficult to detect by ELISA in human serum, due to lack of sensitivity and specificity of currently available assays; 2) human serum interferes with IL-33 quantification, in part through IL-1RL1-a; and 3) using non-serum certified kits may lead to spurious findings. CONCLUSION AND CLINICAL RELEVANCE: If IL-33 is to be studied in the serum of asthma patients and other diseases, a more sensitive and specific assay method is required, which will be vital for further understanding and targeting of the IL-33/IL-1RL1 axis in human disease. PMID- 26850081 TI - In Vitro Engineering of High Modulus Cartilage-Like Constructs. AB - To date, the outcomes of cartilage repair have been inconsistent and have frequently yielded mechanically inferior fibrocartilage, thereby increasing the chances of damage recurrence. Implantation of constructs with biochemical composition and mechanical properties comparable to natural cartilage could be advantageous for long-term repair. This study attempted to create such constructs, in vitro, using tissue engineering principles. Bovine synoviocytes were seeded on nonwoven polyethylene terephthalate fiber scaffolds and cultured in chondrogenic medium for 4 weeks, after which uniaxial compressive loading was applied using an in-house bioreactor for 1 h per day, at a frequency of 1 Hz, for a further 84 days. The initial loading conditions, determined from the mechanical properties of the immature constructs after 4 weeks in chondrogenic culture, were strains ranging between 13% and 23%. After 56 days (sustained at 84 days) of loading, the constructs were stained homogenously with Alcian blue and for type II collagen. Dynamic compressive moduli were comparable to the high end values for native cartilage and proportional to Alcian blue staining intensity. We suggest that these high moduli values were attributable to the bioreactor setup, which caused the loading regime to change as the constructs developed, that is, the applied stress and strain increased with construct thickness and stiffness, providing continued sufficient cell stimulation as further matrix was deposited. Constructs containing cartilage-like matrix with response to load similar to that of native cartilage could produce long-term effective cartilage repair when implanted. PMID- 26850083 TI - Megavoltage conebeam CT cine as final verification of treatment plan in lung stereotactic body radiotherapy. AB - INTRODUCTION: To analyse the clinical impact of megavoltage conebeam computed tomography (MV-CBCT) cine on internal target volume (ITV) coverage in lung stereotactic body radiotherapy (SBRT). METHODS: One hundred and six patients received lung SBRT. All underwent 4D computed tomography simulation followed by treatment via image guided 3D conformal or intensity modulated radiation. Prior to SBRT, all patients underwent MV-CBCT cine, in which raw projections are displayed as beam's-eye-view fluoroscopic series with the planning target volume (PTV) projected onto each image, enabling verification of tumour motion relative to the PTV and assessment of adequacy of treatment margin. RESULTS: Megavoltage conebeam computed tomography cine was completed 1-2 days prior to SBRT. Four patients (3.8%) had insufficient ITV coverage inferiorly at cine review. All four plans were changed by adding 5 mm on the PTV margin inferiorly. The mean change in PTV volumes was 3.9 cubic centimetres (cc) (range 1.85-6.32 cc). Repeat cine was performed after plan modification to ensure adequate PTV coverage in the modified plans. CONCLUSIONS: PTV margin was adequate in the majority of patients with this technique. MV-CBCT cine did show insufficient coverage in a small subset of patients. Insufficient PTV margins may be a function of 4D CT simulation inadequacies or deficiencies in visualizing the ITV inferior border in the full-inhale phase. MV-CBCT cine is a valuable tool for final verification of PTV margins. PMID- 26850084 TI - Abstinence from cocaine-self-administration activates the nELAV/GAP -43 pathway in the hippocampus: A stress-related effect? AB - We previously demonstrated that nELAV/GAP-43 pathway is pivotal for learning and its hippocampal expression is up-regulated by acute stress following repeated cocaine administration. We therefore hypothesized that abstinence-induced stress may sustain nELAV/GAP-43 pathway during early abstinence following 2 weeks of cocaine self-administration. We found that contingent, but not non-contingent, cocaine exposure selectively increases hippocampal nELAV, but not GAP-43, expression immediately after the last self-administration session, an effect that wanes after 24 h and that comes back 7 days later when nELAV activation becomes associated with increased expression of GAP-43, an effect again observed only in animals self-administering the psychostimulant. Such effect is specific for nELAV since the ubiquitous ELAV/HuR is unchanged. This nELAV profile suggests that its initial transient alteration is perhaps related to the daily administration of cocaine, while the increase in the nELAV/GAP-43 pathway following a week of abstinence may reflect the activation of this cascade as a target of stressful conditions associated with drug-related memories. (c) 2016 Wiley Periodicals, Inc. PMID- 26850085 TI - Survival following salvage abdominoperineal resection for persistent and recurrent squamous cell carcinoma of the anus: do these disease categories affect survival? AB - AIM: This study aimed to investigate the results of salvage abdominoperineal excision (APR) in patients with persistent or recurrent squamous cell carcinoma of the anus (SCCA). METHOD: Patients with anal neoplasia were identified from a prospective database. Patients with invasive SCCA with demonstrated failure of chemoradiation therapy (CRT) who underwent salvage APR for one of three disease categories (persistent, < 6 months post-CRT; early recurrent, 6-24 months post CRT; late recurrent, > 24 months post-CRT) were included. The primary outcome was overall survival after salvage APR. Tumour size, metastatic lymph nodes (LN), circumferential resection margin positivity (CRM) and neurolymphovascular invasion (NLVI) were correlated with the outcome. RESULTS: Thirty-six patients with a median 3-year overall survival of 46% (median follow-up 24 months) underwent salvage APR due to persistent or recurrent SCCA (14 men, mean age 59 years). Eleven (31%) patients were diagnosed with persistent disease, 17 (47%) with early and 8 (22%) with late recurrence. Two-year overall survival of Stage 0/I/II and III/IV disease was 81.5% and 33.74%, respectively (P = 0.022). Overall disease stage was associated with disease categorization (P = 0.009): patients with persistent disease or early recurrence had a significantly higher disease stage than patients with late recurrence (OR = 20.9 and 17.2). Despite apparently improved survival in patients with late disease recurrence on live table analysis, no significant difference was identified in overall survival when stratified by disease category on log-rank test analysis. CONCLUSION: Persistent and recurrent disease does not show any significant difference in survival, but patients with late recurrence may have a better prognosis. PMID- 26850086 TI - Novel Glypican-3-Binding Peptide for in Vivo Hepatocellular Carcinoma Fluorescent Imaging. AB - Glypican-3 (GPC3) is a key member of the glypican family that is expressed on the cell surface by a glycosyl-phosphatidyl-inositol (GPI) anchor. It plays a significant role in hepatocellular carcinoma (HCC) development, angiogenesis, and metastasis. Most HCC overexpress GPC3, whereas little GPC3 can be detected in normal adult liver and benign liver lesions. Therefore, it is important to understand the function of GPC3 in HCC tumor development as the GPC3 ligand may facilitate detection of HCC. In this study, a 12-mer peptide with the sequence of DHLASLWWGTEL (denoted as TJ12P1) was identified by screening a phage display peptide library that demonstrated ideal GPC3 binding affinity. We used TJ12P1 conjugated with near-infrared fluorescent (NIFR) dye Cy5.5 for tumor imaging. After intravenous injection of the imaging agent, TJ12P1, xenografts of high GPC3 expressing hepatocellular carcinoma cell line, HepG2, demonstrated significantly higher tumor accumulation (tumor/muscle ratio: 3.98 +/- 0.36) than those of low GPC3 expressing prostate cancer cell line, PC3 (tumor/muscle ratio: 2.03 +/- 0.23). More importantly, GPC3 expression in tumor samples of patients could be visualized using TJ12P1, suggesting the potential use of this peptide as a probe for HCC detection. Our study has successfully identified a promising GPC3-binding peptide ligand for detecting the GPC3 expression in HCC not only in vitro but also in vivo by its noninvasive imaging. PMID- 26850088 TI - Verrucous dermal henneguyosis associated with Henneguya exilis (Kudo, 1929) (Cnidaria: Myxobolidae), a parasite of the channel catfish Ictalurus punctatus (Rafinesque, 1818). PMID- 26850089 TI - Experiences of nursing staff caring for patients with methicillin-resistant Staphylococcus aureus. AB - BACKGROUND: Methicillin-resistant Staphylococcus aureus is a resistant variant of S. aureus and can cause pneumonia, septicaemia and, in some cases, death. Caring for patients with antibiotic resistant bacteria is a challenge for healthcare personnel. There is a risk of spreading the bacteria among patients and of healthcare personnel being infected themselves. AIM: To describe nursing staffs' experiences of caring for patients with methicillin-resistant S. aureus in Sweden. METHOD: A descriptive qualitative approach was used and 15 nurses from different hospitals and care units, including emergency and geriatric wards and nursing homes in Stockholm, were interviewed. All nurses had been involved in the care of patients with methicillin-resistant S. aureus, but not on a regular basis. The interviews were analysed using qualitative content analysis. FINDINGS: Three themes emerged from the data: feeling ignorant, afraid and insecure, feeling competent and secure and feeling stressed and overworked. The more knowledge the nurses acquired about methicillin-resistant S. aureus, the more positive was their attitude to caring for these patients. DISCUSSION AND CONCLUSION: Caring for patients with methicillin-resistant S. aureus without adequate knowledge of how to protect oneself and other patients against transmission may provoke anxiety among personnel. Guidelines, memos and adequate information at the right time are of central importance. Healthcare personnel must feel safe in their role as caregivers. All patients have the right to have the same quality of care regardless of the diagnosis and a lack of knowledge influences the level of care given. IMPLICATIONS FOR NURSING AND HEALTH POLICY: This study demonstrates the importance of education when caring for patients with infectious diseases. Hopefully, knowledge gained from our study can provide guidance for future health care when new diseases and infections occur. PMID- 26850087 TI - Peribiliary Glands as a Niche of Extrapancreatic Precursors Yielding Insulin Producing Cells in Experimental and Human Diabetes. AB - Peribiliary glands (PBGs) are niches in the biliary tree and containing heterogeneous endodermal stem/progenitors cells that can differentiate, in vitro and in vivo, toward pancreatic islets. The aim of this study was to evaluate, in experimental and human diabetes, proliferation of cells in PBGs and differentiation of the biliary tree stem/progenitor cells (BTSCs) toward insulin producing cells. Diabetes was generated in mice by intraperitoneal injection of a single dose of 200 mg/kg (N = 12) or 120 mg/kg (N = 12) of streptozotocin. Liver, pancreas, and extrahepatic biliary trees were en bloc dissected and examined. Cells in PBGs proliferated in experimental diabetes, and their proliferation was greatest in the PBGs of the hepatopancreatic ampulla, and inversely correlated with the pancreatic islet area. In rodents, the cell proliferation in PBGs was characterized by the expansion of Sox9-positive stem/progenitor cells that gave rise to insulin-producing cells. Insulin-producing cells were located mostly in PBGs in the portion of the biliary tree closest to the duodenum, and their appearance was associated with upregulation of MafA and Gli1 gene expression. In patients with type 2 diabetes, PBGs at the level of the hepatopancreatic ampulla contained cells showing signs of proliferation and pancreatic fate commitment. In vitro, high glucose concentrations induced the differentiation of human BTSCs cultures toward pancreatic beta cell fates. The cells in PBGs respond to diabetes with proliferation and differentiation towards insulin-producing cells indicating that PBG niches may rescue pancreatic islet impairment in diabetes. These findings offer important implications for the pathophysiology and complications of this disease. Stem Cells 2016;34:1332-1342. PMID- 26850090 TI - Patients with perianal Crohn's disease have poor disease outcomes after primary bowel resection. AB - BACKGROUND AND AIM: The presence of perianal disease in Crohn's disease patients is one of the factors of postoperative recurrence. The aim of this study is to evaluate long-term prognosis of perianal Crohn's disease patients in Asian. METHODS: Patients with Crohn's disease who had undergone surgical bowel resection were divided into two groups according to the presence of perianal lesion. We monitored the occurrences of abdominal and/or perianal reoperation and readmission due to disease flare-up. RESULTS: The 132 patients included in the study were divided into 2 groups, those with perianal disease (45 patients, 34.1%) and those without perianal disease (87 patients, 65.9%). Patients with perianal disease was younger in age (33.8 years versus 39.8 years, p = 0.015) and had been diagnosed as CD at a younger age (21.9 years versus 28.6 years, p = 0.005) than patients without perianal disease. Patients with perianal disease showed more extra-intestinal manifestation than patients without perianal disease (8 versus 3, p = 0.008). Reoperation was required in 46 (44.8%) patients during the follow-up period. The presence of perianal disease independently increased the risk of reoperation [hazard ratio (HR), 3.112; confidence interval (CI), 1.707-5.675]. Furthermore, patients with perianal disease had increasing risks of abdominal reoperation (HR 1.978; 95% CI, 1.034-3.784). CONCLUSIONS: Patients with Crohn's disease and perianal lesions had a higher risk of reoperation. Considering these findings, physicians should consider aggressive and early top down therapy for patients with perianal Crohn's disease. PMID- 26850092 TI - Virtual substitution scan via single-step free energy perturbation. AB - With the rapid expansion of our computing power, molecular dynamics (MD) simulations ranging from hundreds of nanoseconds to microseconds or even milliseconds have become increasingly common. The majority of these long trajectories are obtained from plain (vanilla) MD simulations, where no enhanced sampling or free energy calculation method is employed. To promote the "recycling" of these trajectories, we developed the Virtual Substitution Scan (VSS) toolkit as a plugin of the open-source visualization and analysis software VMD. Based on the single-step free energy perturbation (sFEP) method, VSS enables the user to post-process a vanilla MD trajectory for a fast free energy scan of substituting aryl hydrogens by small functional groups. Dihedrals of the functional groups are sampled explicitly in VSS, which improves the performance of the calculation and is found particularly important for certain groups. As a proof-of-concept demonstration, we employ VSS to compute the solvation free energy change upon substituting the hydrogen of a benzene molecule by 12 small functional groups frequently considered in lead optimization. Additionally, VSS is used to compute the relative binding free energy of four selected ligands of the T4 lysozyme. Overall, the computational cost of VSS is only a fraction of the corresponding multi-step FEP (mFEP) calculation, while its results agree reasonably well with those of mFEP, indicating that VSS offers a promising tool for rapid free energy scan of small functional group substitutions. (c) 2016 Wiley Periodicals, Inc. Biopolymers 105: 324-336, 2016. PMID- 26850091 TI - Effect of diabetes and acute rejection on liver transplant outcomes: An analysis of the organ procurement and transplantation network/united network for organ sharing database. AB - The effects of diabetic status and acute rejection (AR) on liver transplant outcomes are largely unknown. We studied 13,736 liver recipients from the United Network for Organ Sharing/Organ Procurement Transplant Network database who underwent transplantation between 2004 and 2007 with a functioning graft for greater than 1 year. The association of pretransplant diabetes mellitus (PDM), new-onset diabetes after transplant (NODAT), and AR rates on allograft failure, all-cause mortality, and cardiovascular mortality were determined. To determine the differential and joint effects of diabetic status and AR on transplant outcomes, recipients were further stratified into 6 groups: neither (reference, n = 6600); NODAT alone (n = 2054); PDM alone (n = 2414); AR alone (n = 1448); NODAT and AR (n = 707); and PDM and AR (n = 513). An analysis with hepatitis C virus (HCV) serostatus was also performed (HCV recipients, n = 6384; and non-HCV recipient, n = 5934). The median follow-up was 2537 days. The prevalence of PDM was 21.3%. At 1 year after transplant, the rates of NODAT and AR were 25.5% and 19.4%, respectively. Overall, PDM, NODAT, and AR were associated with increased risks for graft failure (PDM, hazard ratio [HR] = 1.31, P < 0.01; NODAT, HR = 1.11, P = 0.02; AR, HR = 1.28, P < 0.01). A multivariate Cox regression analysis of the 6 recipient groups demonstrated that NODAT alone was not significantly associated with any study outcomes. The presence of PDM, AR, NODAT and AR, and PDM and AR were associated with higher overall graft failure risk and mortality risk. The presence of PDM was associated with higher cardiovascular mortality risk. The analyses in both HCV-positive and HCV-negative cohorts showed a similar trend as in the overall cohort. In conclusion, PDM and AR, but not NODAT, is associated with increased mortality and liver allograft failure. Liver Transplantation 22 796-804 2016 AASLD. PMID- 26850093 TI - Antihypertensive therapy for the prevention of nephropathy in diabetic hypertensive patients. AB - WHAT IS KNOWN AND OBJECTIVE: Although antihypertensive recommendations exist for diabetic nephropathy, there is less guidance for diabetics with normoalbuminuria. Therefore, this review evaluates antihypertensives in preventing nephropathy in diabetic hypertensive patients. COMMENT: A literature search was performed using PubMed and Medline for primary literature from 1978 through August 2015. Search terms included diabetes mellitus, normoalbuminuria, hypertension, ACE inhibitor, ARB and calcium channel blocker. There was no literature evaluating antihypertensive therapies in preventing nephropathy in type 1 hypertensive diabetics. However, in patients with type 2 diabetes and hypertension, multiple studies demonstrate the benefit of an ACEI or ARB in preventing or delaying the onset of nephropathy, while no study demonstrated the benefit of a CCB over an ACEI or ARB. WHAT IS NEW AND CONCLUSION: Due to the lack of literature, hypertension management in type 1 diabetics with normoalbuminuria should be guided by the treatment of comorbidities. To prevent diabetic nephropathy, an ACEI or ARB should be first-line monotherapy over a CCB for the management of hypertension in patients with type 2 diabetes mellitus, hypertension and normoalbuminuria. PMID- 26850095 TI - Integration of biofiltration and advanced oxidation processes for tertiary treatment of an oil refinery wastewater aiming at water reuse. AB - The combination of biological and chemical oxidation processes is an interesting approach to remove ready, poor, and non-biodegradable compounds from complex industrial wastewaters. In this study, biofiltration followed by H2O2/UV oxidation (or microfiltration) and final reverse osmosis (RO) step was employed for tertiary treatment of an oil refinery wastewater. Biofiltration alone allowed obtaining total organic carbon (TOC), chemical oxygen demand (COD), UV absorbance at 254 nm (UV254), ammonium, and turbidity removal of around 46, 46, 23, 50, and 61 %, respectively. After the combined biological-chemical oxidation treatment, TOC and UV254 removal amounted to 88 and 79 %, respectively. Whereas, the treatment performance achieved with different UV lamp powers (55 and 95 W) and therefore distinct irradiance levels (26.8 and 46.3 mW/cm(2), respectively) were very similar and TOC and UV254 removal rates were highly affected by the applied C/H2O2 ratio. Silt density index (SDI) was effectively reduced by H2O2/UV oxidation, favoring further RO application. C/H2O2 ratio of 1:4, 55 W UV lamp, and 20-min oxidation reaction corresponded to the experimental condition which provided the best cost/benefit ratio for TOC, UV254, and SDI reduction from the biofilter effluent. The array of treatment processes proposed in this study has shown to be adequate for tertiary treatment of the oil refinery wastewater, ensuring the mitigation of membrane fouling problems and producing a final effluent which is suitable for reuse applications. PMID- 26850094 TI - Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen induced pulmonary inflammation in mice. AB - BACKGROUND: Accumulation of activated eosinophils in tissue is a hallmark of allergic inflammation. The endocannabinoid 2-arachidonoylglycerol (2-AG) has been proposed to elicit eosinophil migration in a CB2 receptor/Gi/o -dependent manner. However, it has been claimed recently that this process may also involve other mechanisms such as cytokine priming and the metabolism of 2-AG into eicosanoids. Here, we explored the direct contribution of specific CB2 receptor activation to human and mouse eosinophil effector function in vitro and in vivo. METHODS: In vitro studies including CB2 expression, adhesion and migratory responsiveness, respiratory burst, degranulation, and calcium mobilization were conducted in human peripheral blood eosinophils and mouse bone marrow-derived eosinophils. Allergic airway inflammation was assessed in mouse models of acute OVA-induced asthma and directed eosinophil migration. RESULTS: CB2 expression was significantly higher in eosinophils from symptomatic allergic donors. The selective CB2 receptor agonist JWH-133 induced a moderate migratory response in eosinophils. However, short-term exposure to JWH-133 potently enhanced chemoattractant-induced eosinophil shape change, chemotaxis, CD11b surface expression, and adhesion as well as production of reactive oxygen species. Receptor specificity of the observed effects was confirmed in eosinophils from CB2 knockout mice and by using the selective CB2 antagonist SR144528. Of note, systemic application of JWH-133 clearly primed eosinophil-directed migration in vivo and aggravated both AHR and eosinophil influx into the airways in a CB2 specific manner. This effect was completely absent in eosinophil-deficient ?dblGATA mice. CONCLUSION: Our data indicate that CB2 may directly contribute to the pathogenesis of eosinophil-driven diseases. Moreover, we provide new insights into the molecular mechanisms underlying the CB2 -mediated priming of eosinophils. Hence, antagonism of CB2 receptors may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophilic disorders. PMID- 26850096 TI - Promotion of breast cancer cells MDA-MB-231 invasion by di(2-ethylhexyl)phthalate through matrix metalloproteinase-2/-9 overexpression. AB - Di(2-ethylhexyl)phthalate (DEHP) is an estrogenic chemical that is widely used in polyvinyl products. We aimed to determine the mechanisms behind the effects of DEHP on ERalpha-negative breast cancer cells MDA-MB-231 invasion and matrix metalloproteinases-2/-9 (MMP-2/-9) up-regulation in this study. Transwell assay indicated that DEHP exposure (>50 MUg/ml) significantly enhanced the invasion ability of MDA-MB-231 cells. Quantitative real-time PCR (qPCR) and western blotting revealed that MMP-2/-9 is overexpressed in mRNA and protein levels after DEHP treatment. Gelatin zymography consistently demonstrated that DEHP exposure also enhances the activity of MMP-2/-9. Immunofluorescence assay showed that DEHP could accelerate NF-kappaB (NF-kappaB) subunits-p65 translocation into the nucleus, which is confirmed by western blotting assay, suggesting that the ratio of nuclear/cytosolic level of p65 was significantly increased. Furthermore, the invasion and MMP-2/-9 overexpression of MDA-MB-231 cells after DEHP-treated were reversed by the NF-kappaB chemical inhibitor JSH-23 via drug inhibition assay. This study suggested that DEHP could promote ERalpha-negative breast cancer cells MDA-MB-231 invasion through activating NF-kappaB and MMP-2/-9 overexpression. PMID- 26850097 TI - Chemical speciation and bioavailability of cadmium in the temperate and semiarid soils treated with wheat residue. AB - Heavy metal bioavailability depends on metal fractions in soil. The impacts of mild wheat residue (<2 mm) and incubation time on fractions of Cd were studied in two different spiked soils sampled from Hamadan and Lahijan, Iran with semiarid and temperate climates, respectively. Two factorial experiments were done in two soils polluted with 10 MUg Cd g(-1) soil separately. Organic matter (0 and 5 % wheat straw) and soil incubation time (24 and 3600 h) were factors examined in three replicates. The transformation of Cd from KNO3 extractable form to less available fractions was higher in semiarid soils with lower clay and OM contents and higher pH and carbonate contents compared to temperate soils. In polluted semiarid soils after 24 h incubation, greater content of Cd was observed in residual (HNO3 extractable) (45 %), carbonates associated (EDTA extractable) (34 %), organic matter associated (NaOH extractable) (11 %), and KNO3 extractable (10 %) fractions, but in temperate soils, greater content of Cd was observed in KNO3 extractable (61 %), HNO3 extractable (14 %), EDTA extractable (13 %), and NaOH extractable (12 %) fractions. KNO3 extractable form of Cd was decreased, and NaOH extractable and HNO3 extractable forms of Cd were increased by addition of wheat residue to both soils. The initial decrease of added Cd from KNO3 extractable form to less mobile fractions in Hamadan soil was very interesting. But this change was not observed in Lahijan soil. Since contamination factor was significantly high in temperate soils compared to semiarid soils in all treatments, the risk of Cd environmental pollution in temperate region is considerably high. PMID- 26850099 TI - Characterization and source identification of pollutants in runoff from a mixed land use watershed using ordination analyses. AB - While identification of critical pollutant sources is the key initial step for cost-effective runoff management, it is challenging due to the highly uncertain nature of runoff pollution, especially during a storm event. To identify critical sources and their quantitative contributions to runoff pollution (especially focusing on phosphorous), two ordination methods were used in this study: principal component analysis (PCA) and positive matrix factorization (PMF). For the ordination analyses, we used runoff quality data for 14 storm events, including data for phosphorus, 11 heavy metal species, and eight ionic species measured at the outlets of subcatchments with different land use compositions in a mixed land use watershed. Five factors as sources of runoff pollutants were identified by PCA: agrochemicals, groundwater, native soils, domestic sewage, and urban sources (building materials and automotive activities). PMF identified similar factors to those identified by PCA, with more detailed source mechanisms for groundwater (i.e., nitrate leaching and cation exchange) and urban sources (vehicle components/motor oils/building materials and vehicle exhausts), confirming the sources identified by PCA. PMF was further used to quantify contributions of the identified sources to the water quality. Based on the results, agrochemicals and automotive activities were the two dominant and ubiquitous phosphorus sources (39-61 and 16-47 %, respectively) in the study area, regardless of land use types. PMID- 26850098 TI - Development of magnetic graphene oxide adsorbent for the removal and preconcentration of As(III) and As(V) species from environmental water samples. AB - New-generation adsorbent, Fe3O4@SiO2/GO, was developed by modification of graphene oxide (GO) with silica-coated (SiO2) magnetic nanoparticles (Fe3O4). The synthesized adsorbent was characterized using Fourier transform infrared spectroscopy, X-ray diffractometry, energy-dispersive X-ray spectroscopy, and field emission scanning electron microscopy. The developed adsorbent was used for the removal and simultaneous preconcentration of As(III) and As(V) from environmental waters prior to ICP-MS analysis. Fe3O4@SiO2/GO provided high adsorption capacities, i.e., 7.51 and 11.46 mg g(-1) for As(III) and As(V), respectively, at pH 4.0. Adsorption isotherm, kinetic, and thermodynamic were investigated for As(III) and As(V) adsorption. Preconcentration of As(III) and As(V) were studied using magnetic solid-phase extraction (MSPE) method at pH 9.0 as the adsorbent showed selective adsorption for As(III) only in pH range 7-10. MSPE using Fe3O4@SiO2/GO was developed with good linearities (0.05-2.0 ng mL(-1)) and high coefficient of determination (R (2) = 0.9992 and 0.9985) for As(III) and As(V), respectively. The limits of detection (LODs) (3* SD/m, n = 3) obtained were 7.9 pg mL(-1) for As(III) and 28.0 pg mL(-1) for As(V). The LOD obtained is 357-1265* lower than the WHO maximum permissible limit of 10.0 ng mL(-1). The developed MSPE method showed good relative recoveries (72.55-109.71 %) and good RSDs (0.1-4.3 %, n = 3) for spring water, lake, river, and tap water samples. The new-generation adsorbent can be used for the removal and simultaneous preconcentration of As(III) and As(V) from water samples successfully. The adsorbent removal for As(III) is better than As(V). PMID- 26850100 TI - Estimation and risk assessment of flubendiamide on fodder berseem clover (Trifolium alexandrinum L.) by QuEChERS methodology and LC-MS/MS. AB - The residues of flubendiamide from berseem were extracted and cleaned up by the QuEChERS approach and analysed by liquid chromatography/mass spectrometry (LC MS/MS). The dissipation studies on berseem were carried out by application of flubendiamide at five different dosages i.e. 24, 36, 48, 72 and 96 g a.i. ha(-1). The residues reached below determination limit (BDL) of 0.01 mg kg(-1) in 7, 10, 10, 15 and 15 days for 24, 36, 48, 72 and 96 g.a.i. ha(-1)dosages, respectively. Half-life (t1/2) of flubendiamide on berseem was observed to be 1.08, 1.88, 1.94, 2.26 and 2.27 days, respectively, at 24, 36, 48, 72 and 96 g a.i. ha(-1). Theoretical maximum residue contributions (TMRC) values reached below the maximum permissible limit (MPI) for 3, 5 and 7 days in treatments at 24, 36 and 48 g.a.i. ha(-1), respectively, whereas in case of higher dose treatments i.e. 72 and 96 g a.i. ha(-1), the residues of flubendiamide reached below MPI after 10 days of treatment. These data could provide guidance for the proper and safe use of this pesticide on berseem in India. PMID- 26850101 TI - Tu Amigo Pepe: Evaluation of a Multi-media Marketing Campaign that Targets Young Latino Immigrant MSM with HIV Testing Messages. AB - Latino immigrant men who have sex with men (MSM) are at risk for HIV and delayed diagnosis in the United States. This paper describes the evaluation of a pilot of the Tu Amigo Pepe, a multimedia HIV testing campaign aimed at Latino MSM in Seattle, WA particularly targeting immigrants who may not identify as gay, ages 18-30 years old. The 16-week campaign included Spanish-language radio public service announcements (PSAs), a Web site, social media outreach, a reminder system using mobile technology, print materials and a toll-free hotline. In developing the PSAs, the Integrated Behavioral Model was used as a framework to reframe negative attitudes, beliefs and norms towards HIV testing with positive ones as well as to promote self-efficacy towards HIV testing. The campaign had a significant and immediate impact on attitudes, beliefs, norms and self-efficacy towards HIV testing as well as on actual behavior, with HIV testing rates increasing over time. PMID- 26850102 TI - Evaluation of ten prognostic factors affecting the outcome of West syndrome. AB - The aim of this study is to assess the seizure and developmental outcome and to determine the prognostic factors affecting the outcome of West syndrome in an etiologically well-defined large cohort. Demographic features, treatment modalities, etiology, seizure and developmental outcome of 216 cases with West syndrome were recorded retrospectively. Ten prognostic factors possibly affecting the outcome of West syndrome including (1) gender, (2) age at the onset (3) presence of seizures prior to spasms, (4) presence of asymmetric spasm, (5) presence of abnormal neurological signs, (6) treatment lag, (7) etiology, (8) drug chosen as the initial treatment, (9) response to initial treatment regardless of the kind, (10) development of other seizure types after spasms were evaluated in terms of seizure and developmental outcome. Twelve percent of the cases were developmentally normal at the end of 2-year follow-up. Ongoing seizures requiring antiepileptic drug medication at the last follow-up were noted in 90 % of the cases. Hypoxia (29 %), metabolic disorders (11 %), infectious diseases (9 %) and cerebral developmental disorders (8 %) were the most frequent etiological factors. Five of the ten prognostic factors (presence of seizures prior to spasms, presence of abnormal neurological signs, response to initial treatment regardless of the kind, etiology and development of other seizure types after spasms) were found to be statistically significant prognostic factors predicting the outcome. In conclusion, West syndrome is still a catastrophic epileptic encephalopathy. Preventable causes still constitute a substantial portion of the etiological causes of West syndrome. Therefore, the prevention of avoidable causes is at least as important as the treatment. PMID- 26850103 TI - Modeling and in situ measurements of biometeorological conditions in microenvironments within the Athens University Campus, Greece. AB - The objective of this research is to assess and analyze the biometeorological perception in complex microenvironments in the Athens University Campus (AUC) using urban micromodels, such as RayMan. The human thermal sensation in such a place was considered of great significance due to the great gathering of student body and staff of the University. The quantification of the biometeorological conditions was succeeded by the estimation of the physiologically equivalent temperature (PET), which is a biometeorological index based on the human energy balance. We carried out, on one hand, field measurements of air temperature, relative humidity, wind speed, and global solar irradiance for different sites (building atrium, open area, and green atrium) of the examined microurban environment in order to calculate PET during January-July 2013. Additionally, on the other hand, PET modeling was performed using different sky-view factors and was compared to a reference site (meteorological station of Laboratory of Climatology and Atmospheric Environment, University of Athens). The global radiation was transferred to the examined sites with the RayMan model, which considers the sky-view factors for the adaptation of the radiation fluxes to simple and complex environments. The results of this study reveal the crucial importance of the existence of trees and green cover in a complex environment, as a factor that could be the solution to the efforts of stake holders in order to mitigate strong heat stress and improve people's living quality in urban areas. PMID- 26850104 TI - [Global management of patients with ebola viral disease, experience of the Healthcare workers Treatment of Conakry, Guinea]. AB - The Healthcare Workers Treatment Center of Conakry, Guinea, was inaugurated in january 2015. It is dedicated to the diagnosis and the treatment of healthcare workers with probable or confirmed Ebola viral disease. It is staffed by the french army medical service. The french military team may reconcile their medical practice and the ethno-cultural imperatives to optimise the patient adherence during his hospitalization. PMID- 26850105 TI - [Epidemiological and clinical features of cutaneous leishmaniasis in Kairouan Tunisia and characteristics in children]. AB - Cutaneous leishmaniasis (CL) remains highly endemic in Tunisia. The governorate of Kairouan (Center) is one of the most affected particularly by zoonotic form due to Leishmania major. The purpose of this study was to describe the epidemiological, clinical and therapeutic features of the disease in this governorate and to identify any particularities in children. Three hundred and ninety cases were registered over 2 years (2012 and 2013). The average age was 29 years one month [+/- 22.7] (34.6% of patients were under 15 years). The cumulative incidence of CL was equal to 34.4 per 100,000 per year. It was higher in children (39.6 per 100,000 versus 29, p=0.004). Cases were diagnosed especially in autumn and winter (88.3% of cases between October and January, p<0.001). The average delay of consultation was one month and 22 days [+/- 2.5] after onset of lesions. The average number of lesions per patient was 2.7 [+/- 2.3] with a mean diameter equal to 2.2 cm. In addition to a higher incidence of the disease, two other features were found in "Children" group which are the presence of similar cases in the neighborhood (27.7% versus 13.4%, p=0.002) and preferential localization in the face (36.4% versus 11%) while the members were more affected in adults (63.5% versus 46.4%) (p<0.001). Meglumine antimoniate was prescribed for most of our patients (93.1%). The intramuscular route was used more than local one, probably because of high proportions of multiple lesions and facial localization. PMID- 26850106 TI - [Ebola contacts' surveillance: social impact and ethical issues in Senegal]. AB - Quarantine has been widely used during the Ebola outbreak in West Africa mainly to control transmission chains. This measure raises ethical issues that require documentation of the modalities of quarantine at the field level and its social effects for contact persons. In Senegal, 74 people were in contact with the Ebola case coming from Guinea in September 2014. Of these, 34 members of the case's household were contained together at home and monitored by officers. The remaining 40 health care workers from two facilities were dispersed in their family households and monitored by telephone or during doctors' visits. The study is based on in-depth interviews with 43 adult contacts about their experiences and perceptions, with additional observation for interpretation and contextualization.Containment at home was applied differently to contacts who lived with patient zero than to professional health care contacts. No coercion was used at first since all contacts adhered to surveillance, but some of them did not fully comply with movement restrictions. Contacts found biosafety precautions stigmatizing, especially during the first days when health workers and contacts were feeling an acute fear of contagion. The material support that was provided-food and money-was necessary since contacts could not work nor get resources, but it was too limited and delayed. The relational support they received was appreciated, as well as the protection from stigmatization by the police and follow-up workers. But the information delivered to contacts was insufficient, and some of them, including health workers, had little knowledge about EVD and Ebola transmission, which caused anxiety and emotional suffering. Some contacts experienced the loss of their jobs and loss of income; several could not easily or fully return to their previous living routines.Beyond its recommendations to enhance support measures, the study identifies the ethical stakes of quarantine in Senegal regarding informed consent and individual autonomy, non-maleficence and benevolence, and equity and adaptation to specific situations. Nevertheless, the balance between preventive benefits and individual inconveniences of quarantine should still be evaluated from a public health perspective. PMID- 26850107 TI - PlsX deletion impacts fatty acid synthesis and acid adaptation in Streptococcus mutans. AB - Streptococcus mutans, one of the primary causative agents of dental caries in humans, ferments dietary sugars in the mouth to produce organic acids. These acids lower local pH values, resulting in demineralization of the tooth enamel, leading to caries. To survive acidic environments, Strep. mutans employs several adaptive mechanisms, including a shift from saturated to unsaturated fatty acids in membrane phospholipids. PlsX is an acyl-ACP : phosphate transacylase that links the fatty acid synthase II (FASII) pathway to the phospholipid synthesis pathway, and is therefore central to the movement of unsaturated fatty acids into the membrane. Recently, we discovered that plsX is not essential in Strep. mutans. A plsX deletion mutant was not a fatty acid or phospholipid auxotroph. Gas chromatography of fatty acid methyl esters indicated that membrane fatty acid chain length in the plsX deletion strain differed from those detected in the parent strain, UA159. The deletion strain displayed a fatty acid shift similar to WT, but had a higher percentage of unsaturated fatty acids at low pH. The deletion strain survived significantly longer than the parent strain when cultures were subjected to an acid challenge of pH 2.5.The DeltaplsX strain also exhibited elevated F-ATPase activity at pH 5.2, compared with the parent. These results indicate that the loss of plsX affects both the fatty acid synthesis pathway and the acid-adaptive response of Strep. mutans. PMID- 26850108 TI - Malaria in pregnancy: a passive surveillance study of pregnant women in low transmission areas of Colombia, Latin America. AB - BACKGROUND: Malaria causes a significant burden in highly endemic areas where children and pregnant women are more susceptible to severe disease and death, however, in low transmission settings malaria in pregnant women is less frequent. The aim of this study was to provide information of clinical profile, anti parasite host immune responses and parasite genotyping of pregnant women with malaria in low endemic areas of Colombia. METHODS: This was a descriptive study conducted through passive surveillance in 1328 individuals from three endemic areas of Cordoba, Narino and Choco departments between 2011 and 2013. Trained physicians confirmed the pregnancy status and recorded clinical and epidemiological information. Haematological parameters, as well as hepatic and renal function, anti-malarial antibodies and parasite genotypes were evaluated. RESULTS: A total of 582 women presented with malaria infection, 34 of whom were pregnant (5.8 %), and most were infected by Plasmodium falciparum (n = 24). In 44 % (n = 15) of the women, the infection occurred during the first half of pregnancy. Although uncomplicated disease and parasitaemia <=20,000 parasites/uL were common (n = 31), three women (8.8 %) infected by P. falciparum were classified as severe cases. Mild to moderate anaemia (68 %) and mild thrombocytopaenia (41 %) were the most frequent blood alterations and in four women acute renal failure was observed. Six women presented a second malaria episode during pregnancy mainly caused by P. vivax (n = 5), although no direct evidence of relapse was found by genotyping. Two out of the six women presenting a second malaria episode had severe malaria. A low prevalence of specific anti parasite antibodies was found. Microsatellites indicated that all P. vivax infections involved multiple lineages whereas all but one P. falciparum infections harboured single genotypes. CONCLUSIONS: Most malaria infected pregnant women displayed uncomplicated malaria, although a few of them with a second malaria episode presented an increased risk of severe malaria which appeared to be associated with malaria transmission intensity and not with levels of anti-parasite antibodies. The effects of severe malaria in both mother and fetus warrant future studies in low transmission settings. PMID- 26850109 TI - [Operative therapy for rheumatoid arthritis of the hand]. AB - The need for operative treatment of severe rheumatic deformities of the hand and wrist is decreasing due to the increased use of disease-modifying drugs; however, some patients do not tolerate or do not sufficiently respond to these drugs, which often results in the hands being affected and in advanced stages to severe deformity and loss of function. In these cases operative surgery can help to slow the progression of rheumatic destruction and restore the function of the patient's hand. This article describes the principles of surgery for rheumatoid arthritis of the hand. A meticulous synovectomy or tenosynovectomy is the first stage of treatment. With progression of rheumatic destruction various salvage procedures are necessary to preserve the best possible functional state. PMID- 26850110 TI - High mannose-binding Pseudomonas fluorescens lectin (PFL) downregulates cell surface integrin/EGFR and induces autophagy in gastric cancer cells. AB - BACKGROUND: Pseudomonas fluorescens lectin (PFL) belongs to a recently discovered anti-HIV lectin family and induces anoikis-like cell death of MKN28 gastric cancer cells by causing alpha2 integrin internalization through recognition of high mannose glycans; however, the detailed anti-cancer mechanism is not fully elucidated. METHODS: Cell adherence potency of MKN28 upon PFL treatment was assessed using a colorimetric assay. Cell surface molecules to which PFL bound were identified by peptide mass finger printing with Matrix Assisted Laser Desorption/Ionization-time of flight mass spectrometry and their cellular localization determined by immunofluorescence microscopy. Gene and protein expression in PFL-treated MKN28 cells were evaluated by microarray analysis and western blot, and the function of these genes was evaluated by siRNA knock-down. A proliferation assay measured the sensitivity of PFL-treated cancer cells to anti-cancer drugs. The effect of PFL on subcutaneous MKN28 tumor growth and hepatic tumor formation in BALB/c nude mice was evaluated. RESULTS: The strength of MKN28 cell adherence in vitro to the extracellular matrix was impaired by PFL treatment, consistent with the observation that PFL induces rapid downregulation of surface integrins. PFL also was found to bind to cell surface epidermal growth factor receptor (EGFR). Surface EGFR molecules were endocytosed following PFL binding, and were degraded in a time-dependent fashion. This degradation process was largely the result of autophagy, as revealed by the increased expression of autophagic proteins. PFL-induced EGFR degradation was partly inhibited by RAB7 siRNA as well as LC3 siRNA, and internalized EGFR colocalized with ATG9 at 48 h post-PFL treatment, suggesting that these proteins contribute to dynamic degradation induced by PFL. PFL-induced decrease in surface EGFR rendered MKN28 cells susceptible to gefitinib, a selective inhibitor of EGFR tyrosine kinase. In vivo experiments showed that PFL-treated MKN28-EGFP cells injected in the portal vein of BALB/c nude mice failed to form tumor colonies on the liver, and intratumoral injection of PFL significantly inhibited tumor growth. CONCLUSION: PFL-mediated downregulation of integrin and EGFR contributes to the inhibition of tumor growth in vitro and in vivo. This novel anti-cancer mechanism of PFL suggests that this lectin would be useful as an anti-cancer drug or an adjuvant for other drugs. PMID- 26850112 TI - Sobriety and alcohol use among rural Alaska Native elders. AB - BACKGROUND: Although notable health disparities related to alcohol use persist among Alaska Native people living in rural communities, there is a paucity of research examining drinking behaviour in particular segments of this population, including elders. One explanation for this is the distrust of behavioural health research in general and alcohol research in particular following the legacy of the Barrow Alcohol Study, still regarded as a notable example of ethics violations in cross-cultural research. OBJECTIVE: The present study reports findings from one of the first research studies asking directly about alcohol abuse among rural Alaska Natives (AN) since the study in Barrow took place in 1979. DESIGN: We report findings regarding self-reported alcohol use included in an elder needs assessment conducted with 134 Alaska Native elders from 5 rural villages off the road system in Alaska. Data were collected in partnership between academic researchers and community members in accordance with the principles of Community-Based Participatory Research. RESULTS: Findings showed very high rates of sobriety and low rates of alcohol use, contradicting stereotypes of widespread alcohol abuse among AN. Possible explanations and future research directions are discussed. CONCLUSIONS: This research represents one step forward in mending academic-community relationships in rural Alaska to further research on alcohol use and related health disparities. PMID- 26850113 TI - A magnet built on bronchoscopic suction for extraction of tracheobronchial headscarf pins: a novel technique and review of a tertiary centre experience. AB - OBJECTIVES: Airway metal pins are one of the most commonly inhaled foreign bodies in Eastern societies in young females wearing headscarves. We innovated a modified bronchoscopic technique to extract tracheobronchial headscarf pins by the insertion of a magnet to allow an easy and non-traumatic extraction of the pins. The aim of this study was to assess the feasibility and safety of our new technique and compare it with our large previous experience with the classic bronchoscopic method of extraction of tracheobronchial headscarf pins. METHODS: We performed a study comparing our retrospective experience of classic bronchoscopic extraction from February 2004 to January 2014 and prospective experience with our modified technique using the magnet from January 2014 to June 2015. An institutional review board and new device approval were obtained. RESULTS: Three hundred and twenty-six procedures on 315 patients were performed during our initial 10-year experience. Of them, 304 patients were females. The median age of our group was 13 (0-62). The median time from inhalation to procedure was 1 day (0-1022). After introducing our modified new technique using the magnet, 20 procedures were performed. Nineteen were females. The median time of the procedure and the need to forcefully bend the pin for extraction were in favour of the new technique in comparison with our classic approach (2 vs 6 min; P < 0.001) (2 patients = 20% vs 192 = 58%; P < 0.001). The conversion rate to surgery was also in favour of the modified technique but did not reach statistical significance (0 = 0% vs 15 = 4.8%; P = 0.32). All patients who underwent the modified technique were discharged home on the same day of the procedure. No procedural complications were recorded. All remain well on a follow up period of up to 14 months. CONCLUSIONS: Bronchoscopic extraction of tracheobronchial inhaled headscarf pins using a novel technique using homemade magnets was safer and simpler in comparison with our large experience with the classic approach. We advise the use of this device (or concept) in selected patients in centres dealing with this problem. PMID- 26850111 TI - Long term follow-up of cervical intervertebral disc herniation inpatients treated with integrated complementary and alternative medicine: a prospective case series observational study. AB - BACKGROUND: Symptomatic cervical intervertebral disc herniation (IDH) presenting as neck pain accompanied by arm pain is a common affliction whose prevalence continues to rise, and is a frequent reason for integrative inpatient care using complementary and alternative medicine (CAM) in Korea. However, studies on its long term effects are scarce. METHODS: A total 165 patients with cervical IDH admitted between January 2011 and September 2014 to a hospital that provides conventional and Korean medicine integrative treatment with CAM as the main modality were observed in a prospective observational study. Patients underwent CAM treatment administered by Korean medicine doctors (KMDs) in accordance with a predetermined protocol for the length of hospital stay, and additional conventional treatment by medical doctors (MDs) as referred by KMDs. Short term outcomes were assessed at discharge and long term follow-ups were conducted through phone interviews after discharge. Numeric rating scale (NRS) of neck and radiating arm pain, neck disability index (NDI), 5-point patient global impression of change (PGIC), and factors influencing long term satisfaction rates in PGIC were assessed. RESULTS: Of 165 patients who received inpatient treatment 20.8 +/- 11.2 days, 117 completed the long term follow-up up at 625.36 +/- 196.7 days post-admission. Difference in NRS between admission and discharge in the long term follow-up group (n = 117) was 2.71 (95% CI, 2.33, 3.09) for neck pain, 2.33 (95% CI, 1.9, 2.77) for arm pain, and that of NDI 14.6 (95% CI, 11.89, 17.32), and corresponding scores in the non-long term follow-up group (n = 48) were 2.83 (95% CI, 2.22, 3.45) for neck pain, 2.48 (95% CI, 1.84, 3.12) for arm pain, and that of NDI was 14.86 (95% CI, 10.41, 19.3). Difference in long term NRS of neck pain and arm pain from baseline was 3.15 (95% CI, 2.67, 3.64), and 2.64 (95% CI, 1.99, 3.29), respectively. PGIC was reported to be "satisfactory" or higher in 79.5% of patients at long term follow-up. CONCLUSIONS: Though the observational nature of this study limits us from drawing a more decisive conclusion, these results suggest that integrative treatment focused on CAM in cervical IDH inpatients may achieve favorable results in pain and functional improvement. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02257723. Registered October 2, 2014. PMID- 26850114 TI - Occult peripheral artery disease is common and limits the benefit achieved in cardiac rehabilitation. AB - Cardiac rehabilitation (CR) has proven morbidity and mortality benefits in cardiovascular disease, which directly correlates with exercise performance achieved. Many patients in CR exercise at sub-optimal levels, without obvious limitations. Occult lower-extremity peripheral artery disease (PAD) may be a determinant of diminished exercise capacity and reduced benefit obtained from traditional CR. In this prospective study of 150 consecutive patients enrolled in Phase II CR, we describe the prevalence of PAD, the utility of externally validated screening questionnaires, and the observed impact on CR outcomes. Abnormal ankle-brachial indices (ABI) (< 0.9 and >1.4) were observed in 19% of those studied. The Edinburgh Claudication Questionnaire was insensitive for detecting PAD by low ABI in this population, and the Walking Impairment Questionnaire and a modified Gardner protocol demonstrated a lack of typical symptoms with low levels of activity. Importantly, at completion of traditional CR, exercise improvement measured in metabolic equivalents (METs) was worse in those with a low ABI compared to those with a normal ABI (+1.39 vs +2.41 METs, p = 0.002). In conclusion, PAD is common in patients in Phase II CR and often clinically occult. Screening based on standard questionnaires appears insensitive in this population, suggesting a need for a broad-based screening strategy with ABI measurements. In this study, undiagnosed PAD significantly attenuated improvements in exercise performance, which potentially has bearings on future clinical events. PMID- 26850115 TI - Impact of sarcopenia on long-term mortality following endovascular aneurysm repair. AB - Sarcopenia, also known as a reduction of skeletal muscle mass, is a patient specific risk factor for vascular and cancer patients. However, there are no data on abdominal aortic aneurysm (AAA) patients treated with endovascular aneurysm repair (EVAR) who have sarcopenia. To determine the impact of sarcopenia on mortality following EVAR, we retrospectively reviewed 200 patients treated with EVAR by estimating muscle mass on abdominal computed tomography (CT) scans. Mortality was analyzed according to its presence (n=25) or absence (n=175). Sarcopenia was more common in women than men (32.0% vs 9.7%; p=0.005). Patients with sarcopenia had an increased risk of mortality compared to those without (76% vs 48%; p=0.016). Of note, the overall mortality rate was 51% with a median follow up of 8.4 years (interquartile range, 5.3-11.7). In conclusion, the presence of sarcopenia on a CT scan is an important predictor of long-term mortality in patients treated for AAA with EVAR. Pending further study, these data suggest that sarcopenia may aid in pre-procedural long-term survival assessment of patients undergoing EVAR. PMID- 26850116 TI - Extreme low-lying carotid bifurcations. PMID- 26850117 TI - The association between a novel polymorphism (rs1062577) in ESR1 and breast cancer susceptibility in the Han Chinese women. AB - OBJECTIVE: The aim of the present study was to analyze the genetic association between the three estrogen receptor 1 (ESR1) single nucleotide polymorphisms (SNPs; rs1062577, rs2881766, and rs9479118) and breast cancer risk in Han Chinese women. METHODS/MATERIALS: To investigate the possible association of genetic polymorphisms of any of the three ESR1 SNPs in breast cancer patients (n = 198) and healthy controls (n = 218) collected from the college hospital, peripheral blood mononuclear cells samples were analyzed by high-resolution melt-polymerase chain reaction. Odds ratios and 95% confidence intervals were used to evaluate the association between the ESR1 SNPs and breast cancer. RESULTS: Patients genotyped AA for ESR1 rs1062577 showed increased breast cancer risk (p = 0.005). In the menarche at <= 13-year-old group, there were significant differences in alleles A versus T at rs1062577 and alleles G versus T at rs2881766 between the breast cancer group and the control group. In the > 13-year-old group, the AA genotype at rs1062577, the GG genotype at rs2881766, and the CC genotype at rs9479118 increased breast cancer susceptibility. CONCLUSIONS: These results showed that the ESR1 rs1062577 polymorphism increased breast cancer risk in Han Chinese women, which might be used as a new SNP marker. PMID- 26850118 TI - 'A Friend in the Corner': supporting people at home in the last year of life via telephone and video consultation-an evaluation. AB - OBJECTIVE: To evaluate 'Gold Line', a 24/7, nurse-led telephone and video consultation support service for patients thought to be in the last year of life in Bradford, Airedale, Wharfedale and Craven. METHOD: Data on the time and nature of all calls between 1 April 2014 and 30 March 2015 were obtained from the patient Electronic Records. Interviews with 13 participants captured patients and carers perspectives. RESULTS: To date, 3291 patients have been referred to the Gold Line. During the study period, 42% of registered patients had a non-cancer diagnosis and 45.2% of service users were not known to Specialist Palliative Care services. The median time on the caseload was 49 days (range 1-504 days). 4533 telephone calls and 573 video consultations were made involving 1813 individuals. 39% of the 5106 contacts were resolved by the Gold Line team without referral to other services. 69% of calls were made outside normal working hours. Interviews with patients and carers reported experiences of support and reassurance from the Gold Line and the importance of practical advice was emphasised. Current data (year to October 2015) show that 98.5% of calls (4500/4568) resulted in patients remaining in their place of residence. CONCLUSIONS: A nurse led, 24/7 telephone and video consultation service can provide valuable support for patients identified to be in the last year of life and for their carers. The line enabled them to feel supported and remain in their place of residence, hence reducing the pressure for avoidable hospital admissions and use of other services. Providing this service may encourage healthcare professionals to identify more patients approaching the last year of life, widening support offered to this group of patients beyond those known to specialist palliative care services. PMID- 26850119 TI - Mesenchymal Stem Cells as Treatment for Behavioral Deficits and Neuropathology in the 5xFAD Mouse Model of Alzheimer's Disease. AB - Alzheimer's disease (AD) is characterized by a progressive loss of memory and other cognitive disturbances. The neuropathology of AD includes the major hallmarks of toxic amyloid-beta oligomer accumulation and neurofibrillary tangles, as well as increased oxidative stress, cholinergic dysfunction, synapse loss, changes in endogenous neurotrophic factors, and overall degeneration of the brain. Adult mesenchymal stem cells (MSCs) offer the potential for a readily available treatment that would be long lasting, have low likelihood of rejection, and could target a variety of pathological deficits. MSCs have been shown to be effective in alleviating symptoms in some transgenic models of AD, but the optimal location for transplanting MSCs has yet to be determined. In the present study, the behavioral effects of transplantation of MSCs into the lateral ventricles, the hippocampus, or both of these regions were compared in the 5xFAD mouse model of AD. The results indicate that MSC transplants effectively reduce learning deficits in the 5xFAD mouse model and demonstrate a clear impact of MSCs on the levels of Abeta42 in the brains of 5xFAD mice. Overall, these findings support the hypothesis that MSCs may be a viable treatment for AD, especially when injected into the lateral ventricles. PMID- 26850120 TI - CCGs told to delay signing L1.2bn deal on cancer and end of life services. PMID- 26850122 TI - Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes. AB - Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost, outcomes, and incremental cost-utility. PMID- 26850121 TI - Pharmacological effects of meldonium: Biochemical mechanisms and biomarkers of cardiometabolic activity. AB - Meldonium (mildronate; 3-(2,2,2-trimethylhydrazinium)propionate; THP; MET-88) is a clinically used cardioprotective drug, which mechanism of action is based on the regulation of energy metabolism pathways through l-carnitine lowering effect. l-Carnitine biosynthesis enzyme gamma-butyrobetaine hydroxylase and carnitine/organic cation transporter type 2 (OCTN2) are the main known drug targets of meldonium, and through inhibition of these activities meldonium induces adaptive changes in the cellular energy homeostasis. Since l-carnitine is involved in the metabolism of fatty acids, the decline in its levels stimulates glucose metabolism and decreases concentrations of l-carnitine related metabolites, such as long-chain acylcarnitines and trimethylamine-N-oxide. Here, we briefly reviewed the pharmacological effects and mechanisms of meldonium in treatment of heart failure, myocardial infarction, arrhythmia, atherosclerosis and diabetes. PMID- 26850123 TI - Factors Affecting Clinical Outcome in Patients With Structural Failure After Arthroscopic Rotator Cuff Repair. AB - PURPOSE: (1) To compare clinical outcomes between patients with large or massive rotator cuff tears who have healed cuffs and patients with postoperative structural failure (retear after complete or partial repair) and (2) to identify factors associated with clinical outcomes in patients with postoperative structural failure. METHODS: We conducted a retrospective study of consecutive patients with large or massive cuff tears who underwent arthroscopic repair at our institution between 2005 and 2012. On the basis of intraoperative findings and magnetic resonance imaging at final follow-up, the patients were divided into 3 groups: healed group, retear group (after complete repair), and partial-repair group. The outcome measures comprised the Japanese Orthopaedic Association (JOA) and University of California, Los Angeles (UCLA) scores; muscle strength; and range of motion. The tear length, tear width, muscle atrophy, and fatty degeneration were evaluated by preoperative and postoperative magnetic resonance imaging. The extent of tendon reattachment to the superior, middle, and inferior facets and the lesser tuberosity was examined on magnetic resonance images at final follow-up. RESULTS: In total, 74 patients (healed, 41; retear, 19; and partial repair, 14) were included in this study. The mean age was 63.8 +/- 8.5 years, with a mean follow-up period of 3.6 +/- 1.4 years. The postoperative JOA and UCLA scores significantly improved in all 3 groups, but the differences were not significant. In the retear and partial-repair groups, postoperative tendon preservation at the middle facet significantly affected the JOA and UCLA scores (P = .003 and P = .014, respectively). CONCLUSIONS: The JOA and UCLA scores were significantly improved in patients with structural failure. Under these conditions, the only clinical factor that affected patient outcome was tendon healing at the middle facet. Thus tendon preservation at the middle facet was a predictor of good clinical outcomes in patients who underwent arthroscopic rotator cuff repair of large or massive tears and had postoperative structural failure. LEVEL OF EVIDENCE: Level III, case-control study. PMID- 26850124 TI - The replacement of assertive outreach services by reinforcing local community teams: a four-year observational study. AB - BACKGROUND: The introduction of specialist Assertive Outreach (AO) teams has produced only modest differential findings from English studies compared to standard care. Providers have gradually closed AO services over the last 8 years. We previously studied outcomes at 12 months following the dismantling of two AO teams in London. We now report on the longer term outcomes for these patients. AIMS: To evaluate the longer term outcomes, activity and costs for patients receiving a less intensive service. METHODS: Observational service level evaluation of 112 patients comparing baseline of AO care with each year of routine care subsequent to the team closure. RESULTS: Patients transferred to standard teams reinforced with the Flexible Assertive Community Treatment (FACT) approach had significantly fewer admissions and bed days at each of the four subsequent years compared to baseline, offset by a significant rise in missed face-to-face appointments. There was no significant change in the use of crisis services. Predictably patients had significantly fewer contacts under standard care. CONCLUSIONS: AO patients are remarkably resilient to substantial reductions in the intensity of care. Reinforcing multi-disciplinary community mental health teams (CMHTs) with FACT appears to provide an integrated service that is clinically effective and an affordable alternative to orthodox AO teams. PMID- 26850125 TI - Pediatric Sudden Unexpected Death in Epilepsy. AB - BACKGROUND: Epilepsy is a common neurological disorder among children and adolescents that is associated with increased mortality for numerous reasons. Sudden unexpected death in epilepsy is a critically important entity for physicians who treat patients with epilepsy. Many pediatric neurologists are hesitant to discuss this condition with patients and families because of the lower risk in the pediatric age group. METHODS: We searched for studies published between January 2000 and June 2015 by means of a PubMed search and a cumulative review of reference lists of all relevant publications, using the keywords "sudden unexpected death in epilepsy patients," "pediatric SUDEP," "sudden unexpected death in epilepsy patients and children," "sudden unexpected death in children" and "sudden infant death syndrome." RESULTS: SUDEP is a rare condition in children. Its mechanism is poorly understood and may have a distinct pathogenesis from adult sudden unexpected death in epilepsy. Limited comfort, experience, and knowledge to provide appropriate education about sudden unexpected death in epilepsy leads to fewer physicians discussing this subject leading to less informed and less prepared patients and families. CONCLUSION: We provide a detailed review of the literature on pediatric SUDEP, including the definition, classification, and proposed mechanisms of sudden unexpected death in epilepsy in children, as well as discuss the incidence in the pediatric population and risk factors in children, concluding with possible prevention strategies. PMID- 26850126 TI - Neuroprotective effect of ethyl pyruvate against Zn(2+) toxicity via NAD replenishment and direct Zn(2+) chelation. AB - Ethyl pyruvate (EP) is a simple aliphatic ester of pyruvic acid and has been shown to have robust protective effect in various pathological conditions. A variety of mechanisms have been reported to underlie the protective effects of EP, which include anti-inflammatory, anti-oxidative, and anti-apoptotic functions. Recently, we reported that EP suppressed high mobility group box 1 (HMGB1) release from primary microglial cells via direct Ca(2+) chelation. In the present study, we investigated whether and how EP chelates Zn(2+) in neurons when it is present at toxic levels. In cortical neurons treated with 40 MUM of Zn(2+) for 24 h, both EP and pyruvate significantly suppressed neuronal cell death, although the potency of pyruvate was greater than that of EP, and that NAD replenishment contributed to the neuroprotective effects of both pyruvate and EP. However, when cortical neurons were exposed to acute treatment of Zn(2+) (400 MUM, 15 min), EP, but not pyruvate, significantly suppressed neuronal death, despite the fact that NAD replenishment by EP was weaker than that by pyruvate. Spectrophotometric studies revealed that EP directly chelates Zn(2+), and this was confirmed in physiological contexts, such as, NMDA-treated primary cortical cultures and OGD-subjected hippocampal slice cultures, in which EP suppressed intracellular Zn(2+) elevation and neuronal cell death. In addition, EP markedly reduced the expressions of PARP-1 and of the NADPH oxidase subunit in Zn(2+) treated primary cortical neurons, well known Zn(2+)-induced downstream processes. Together, these results show EP suppresses Zn(2+) induced neurotoxicity via dual functions, chelating Zn(2+) and promoting NAD replenishment. PMID- 26850127 TI - Roles of signaling and transcriptional networks in pathological lymphangiogenesis. AB - Lymphangiogenesis, the generation of new lymphatic vessels, plays important roles in cancer metastasis. Outstanding progress during the past decade has dramatically increased the novel knowledge and insights of the mechanisms underlying the generation of new lymphatic vessels, the roles of transcription factors and lymphangiogenic growth factors during physiological development and pathological processes such as cancer and inflammation. Furthermore, an understanding of the molecular consequences during tumor lymphangiogenesis has provided chances to develop better diagnostic and therapeutic approaches that aim to limit the progression of cancer. In this article, we will explain the current knowledge of how lymphatic function is altered in various pathological conditions including cancer progression. PMID- 26850130 TI - The history of human cytogenetics in India-A review. AB - It is 60years since the discovery of the correct number of chromosomes in 1956; the field of cytogenetics had evolved. The late evolution of this field with respect to other fields is primarily due to the underdevelopment of lenses and imaging techniques. With the advent of the new technologies, especially automation and evolution of advanced compound microscopes, cytogenetics drastically leaped further to greater heights. This review describes the historic events that had led to the development of human cytogenetics with a special attention about the history of cytogenetics in India, its present status, and future. Apparently, this review provides a brief account into the insights of the early laboratory establishments, funding, and the German collaborations. The details of the Indian cytogeneticists establishing their labs, promoting the field, and offering the chromosomal diagnostic services are described. The detailed study of chromosomes helps in increasing the knowledge of the chromosome structure and function. The delineation of the chromosomal rearrangements using cytogenetics and molecular cytogenetic techniques pays way in identifying the molecular mechanisms involved in the chromosomal rearrangement. Although molecular cytogenetics is greatly developing, the conventional cytogenetics still remains the gold standard in the diagnosis of various numerical chromosomal aberrations and a few structural aberrations. The history of cytogenetics and its importance even in the era of molecular cytogenetics are discussed. PMID- 26850129 TI - Track Recurrence After Robotic Transaxillary Thyroidectomy: A Case Report Highlighting the Importance of Controlled Surgical Indications and Addressing Unprecedented Complications. AB - BACKGROUND: Robot-assisted transaxillary thyroid surgery (RATS), widely accepted and used in Asian countries, can be an appealing treatment option both for patients with major concerns regarding a cervical scar and for their surgeons. Patients benefit from scarless neck surgery, while their surgeons benefit from improved dexterity and ergonomics compared with remote-access endoscopic thyroid surgery. However, validating any novel surgical procedure for thyroid pathology should be based on evidence regarding its feasibility, radicality, and safety compared to the time-honored, safe and effective, conventional open thyroidectomy. It should also be evaluated for potential risks that are not present with conventional approaches. PATIENT FINDINGS: This study reports a patient with surgical track and cervical nodal recurrence, and distant metastasis following a two-stage robot-assisted surgery, and radioactive iodine ablation therapy for a papillary thyroid carcinoma that was initially regarded a single indeterminate nodule. SUMMARY: This case emphasizes the importance of thoroughly evaluating the oncological safety of RATS, and points out the possibility of "malignant seeding along the surgical access" being an untraditional potential complication associated with the procedure. CONCLUSIONS: While tailoring the surgical strategy to the patients' concerns and desires is important, adhering to fundamental onco-surgical principles is a priority. Furthermore, unconventional complications associated with novel surgical procedures should be properly evaluated and addressed. PMID- 26850128 TI - Saccharomyces cerevisiae as a tool for mining, studying and engineering fungal polyketide synthases. AB - Small molecule secondary metabolites produced by organisms such as plants, bacteria, and fungi form a fascinating and important group of natural products, many of which have shown promise as medicines. Fungi in particular have been important sources of natural product polyketide pharmaceuticals. While the structural complexity of these polyketides makes them interesting and useful bioactive compounds, these same features also make them difficult and expensive to prepare and scale-up using synthetic methods. Currently, nearly all commercial polyketides are prepared through fermentation or semi-synthesis. However, elucidation and engineering of polyketide pathways in the native filamentous fungi hosts are often hampered due to a lack of established genetic tools and of understanding of the regulation of fungal secondary metabolisms. Saccharomyces cerevisiae has many advantages beneficial to the study and development of polyketide pathways from filamentous fungi due to its extensive genetic toolbox and well-studied metabolism. This review highlights the benefits S. cerevisiae provides as a tool for mining, studying, and engineering fungal polyketide synthases (PKSs), as well as notable insights this versatile tool has given us into the mechanisms and products of fungal PKSs. PMID- 26850131 TI - Oral mucosal stigmata in hereditary-cancer syndromes: From germline mutations to distinctive clinical phenotypes and tailored therapies. AB - Numerous familial tumor syndromes are associated with distinctive oral mucosal findings, which may make possible an early diagnosis as an efficacious marker for the risk of developing visceral malignancies. In detail, Familial Adenomatous Polyposis (FAP), Gardner syndrome, Peutz-Jeghers syndrome, Cowden Syndrome, Gorlin Syndrome, Lynch/Muir-Torre Syndrome and Multiple Endocrine Neoplasia show specific lesions of the oral mucosa and other distinct clinical and molecular features. The common genetic background of the above mentioned syndromes involve germline mutations in tumor suppressor genes, such as APC, PTEN, PTCH1, STK11, RET, clearly implied in both ectodermal and mesodermal differentiation, being the oral mucosal and dental stigmata frequently associated in the specific clinical phenotypes. The oral and maxillofacial manifestations of these syndromes may become visible several years before the intestinal lesions, constituting a clinical marker that is predictive for the development of intestinal polyps and/or other visceral malignancies. A multidisciplinary approach is therefore necessary for both clinical diagnosis and management of the gene-carriers probands and their family members who have to be referred for genetic testing or have to be investigated for the presence of visceral cancers. PMID- 26850133 TI - Role of Akt inhibition on Notch1 expression in hepatocellular carcinoma: potential role for dual targeted therapy. AB - BACKGROUND: We have shown that an Akt inhibitor, MK2206, reduces hepatocellular carcinoma (HCC) proliferation. To further delineate MK2206, we sought to investigate the Notch1 pathway and hypothesize that MK2206 treatment will result in Notch1 inhibition with either subsequent or parallel Akt suppression. METHODS: HCC cell lines were treated with various concentrations of MK2206. Cell proliferation was determined via real-time live cell imaging. Knockdown of Notch1 was used to observe interaction between Notch1 and pAkt. Cell lysates were analyzed via Western blotting for Notch and Akt pathway targets. RESULTS: After treatment with MK2206 (up to 2 MUM), there was a 60% reduction in cell viability at 48 hours with a concomitant reduction in Notch1 expression. Knockdown of Notch1 in HCC cell lines correlated with reduction in Akt phosphorylation. CONCLUSIONS: MK2206 inhibits both the PI3-K/Akt and Notch1 pathways. Therefore, further characterization of MK2206 comparing the 2 pathways is warranted and the effect of dual targeting in HCC. PMID- 26850132 TI - Identification of proteasome subunit beta type 2 associated with deltamethrin detoxification in Drosophila Kc cells by cDNA microarray analysis and bioassay analyses. AB - Insecticide deltamethrin resistance has presented a difficult obstacle for pest control and the resistance development is complex and associated with many genes. To better understand the possible molecular mechanisms involved in DM stress, in this study, cDNA microarray analysis was employed. 448 differentially expressed genes with at least a 2-fold expression difference were identified in Drosophila cells after DM exposure. Moreover, some genes were confirmed with qPCR, which yielded results consistent with the microarray analysis. Three members of the ubiquitin-proteasome system were significantly elevated in DM-stressed cells, suggesting that the ubiquitin-proteasome pathway may play an important role in DM detoxification. The proteasome beta2 subunit (Prosbeta2) is a member of 20S proteasome subunit family, which forms the proteolytic core of 26S proteasome. Whether Prosbeta2 participates in DM detoxification requires further study. RNAi and heterologous expression were conducted to investigate the contribution of Prosbeta2 in DM detoxification. The results revealed Prosbeta2 knockdown significantly reduce the level of DM detoxification in RNAi-treated cells after 48 h. Overexpression of Prosbeta2 increased cellular viability. These detoxification results represent the first evidence that Prosbeta2 plays a role in the detoxification of DM, which may provide new idea and target for studying the molecular mechanisms of insect resistance. PMID- 26850134 TI - Mending a broken heart?: Commentary on Joseph et al, "Identifying the Broken Heart...". PMID- 26850135 TI - Abdominal closure protocol in colorectal, gynecologic oncology, and urology procedures: a randomized quality improvement trial. AB - BACKGROUND: Prevention of surgical site infections (SSIs) can improve surgical quality through reductions in morbidity and cost. We sought to determine whether the abdominal closure protocol, in isolation, decreases SSI at an academic teaching hospital. METHODS: Adult patients undergoing laparotomy were prospectively randomized to an abdominal closure protocol, which includes unused sterile instruments and equipment at fascial closure, or usual care. A 30-day SSI rates were compared. General surgery, colorectal, urology, or gynecologic oncology patients undergoing anticipated wound classification II cases were eligible. RESULTS: Overall SSI rates were 11.6% in patients randomized to protocol closure vs 12.4% for usual care (total n = 233; P = .85). The abdominal closure protocol and usual care groups had similar rates of superficial (4.5% vs 4.1%; P = .9), deep (.9% vs 0%, P = .3), organ-space SSI rates (6.2% vs 8.3%, P = .55), and wound dehiscence (2.7% vs 5.3%; P = .24). CONCLUSIONS: An abdominal closure protocol did not decrease the rate of SSI and is likely not a key intervention for SSI reduction. PMID- 26850136 TI - Accuracy and content of medical student midclerkship self-evaluations. AB - BACKGROUND: Midclerkship self-evaluations (MCSEs) require students to reflect on their knowledge, skills, and behaviors. We hypothesized that MCSEs would be consistent with supervisor midpoint evaluations during a surgical clerkship. METHODS: MCSEs of 153 students who completed our surgery clerkship in 2 academic years were compared with supervisor midclerkship evaluations. The quantitative domains of the MCSE and supervisor evaluation were compared for accuracy. Identified areas of strengths and weakness were evaluated for thematic consistency. RESULTS: Student MCSE scoring was accurate across evaluated domains most of the time; when students were inaccurate, they tended to underrate themselves. Students and supervisors most often identified cognitive skills as areas for improvement and noncognitive skills predominated as student strengths. CONCLUSIONS: Medical students can accurately identify their strengths and weaknesses in the context of an MCSE. Based on these findings, knowledge acquisition and application by medical students in the clinical setting should be emphasized in undergraduate medical education. PMID- 26850137 TI - A proposal for a psychopharmacology-pharmacotherapy catalogue of learning objectives and a curriculum in Europe. AB - Objectives Post-graduate training for specialisation in psychiatry and psychotherapy is part of a 4-6-year programme. This paper aims to inform on the general situation of teaching and training of psychopharmacology psychopharmacotherapy in Europe. It presents the need for a psychopharmacotherapy education in psychiatric training programmes. Arguments as well as a proposal for a catalogue of learning objectives and an outline of a psychopharmacology curriculum are presented. Methods Based on their experience and on an analysis of the literature, the authors, experts in psychopharmacology-pharmacotherapy teaching, critically analyse the present situation and propose the development of a curriculum at the European level. Results Teaching programmes vary widely between European countries and, generally, teaching of psychopharmacology and pharmacotherapy does not exceed two-dozen hours. This is insufficient if one considers the central importance of psychopharmacology. A psychopharmacology psychopharmacotherapy curriculum for the professional training of specialists in psychiatry and psychotherapy is proposed. Conclusions As the number of hours of theoretical teaching and practical training is insufficient, a catalogue of learning objectives should be established, which would then be part of a comprehensive curriculum at the European level. It could be inspired partly by those few previously proposed by other groups of authors and organisations. PMID- 26850138 TI - Role of OATP2A1 in PGE(2) secretion from human colorectal cancer cells via exocytosis in response to oxidative stress. AB - Chronic inflammation induced by reactive oxygen species is associated with increased risk of developing colorectal cancer (CRC), and prostaglandin E2 (PGE2), which serves as a key mediator of inflammatory responses, plays an important role in CRC initiation and progression. Therefore, in the present study, we aimed to investigate the role of prostaglandin transporter OATP2A1/SLCO2A1 in the changes of PGE2 disposition in CRC cells in response to oxidative stress. H2O2 induced translocation of cytoplasmic OATP2A1 to plasma membranes in LoVo and COLO 320DM cells, but not in Caco-2 cells. The shift of subcellular OATP2A1 was abolished in the presence of anti-oxidant N-acetyl-L cysteine or an inhibitor of protein kinase C, which evokes exocytosis. Exposure of LoVo cells to H2O2 caused an increase in the amount of extracellular PGE2 without changing the sum of intra- and extracellular PGE2. OATP2A1 knockdown decreased extracellular PGE2 in LoVo cells. In addition, extracellular PGE2 was significantly reduced by exocytosis inhibitor cytochalasin D, suggesting that H2O2-induced PGE2 release occurs in an exocytotic manner. Furthermore, mRNA expression of vascular endothelial growth factor (VEGF) was significantly reduced in LoVo cells by knockdown of OATP2A1. These results suggest that cytoplasmic OATP2A1 likely facilitates PGE2 loading into suitable intracellular compartment(s) for efficient exocytotic PGE2 release from CRC cells exposed to oxidative stress. PMID- 26850139 TI - Editorial. PMID- 26850140 TI - [Collision tumors]. PMID- 26850141 TI - [Familial multiple comedones and PEN-2 mutation]. PMID- 26850142 TI - A simplified strategy for sensitive detection of Rose rosette virus compatible with three RT-PCR chemistries. AB - Rose rosette disease is a disorder associated with infection by Rose rosette virus (RRV), a pathogen of roses that causes devastating effects on most garden cultivated varieties, and the wild invasive rose especially Rosa multiflora. Reliable and sensitive detection of this disease in early phases is needed to implement proper control measures. This study assesses a single primer-set based detection method for RRV and demonstrates its application in three different chemistries: Endpoint RT-PCR, TaqMan-quantitative RT-PCR (RT-qPCR) and SYBR Green RT-qPCR with High Resolution Melting analyses. A primer set (RRV2F/2R) was designed from consensus sequences of the nucleocapsid protein gene p3 located in the RNA 3 region of RRV. The specificity of primer set RRV2F/2R was validated in silico against published GenBank sequences and in-vitro against infected plant samples and an exclusivity panel of near-neighbor and other viruses that commonly infect Rosa spp. The developed assay is sensitive with a detection limit of 1fg from infected plant tissue. Thirty rose samples from 8 different states of the United States were tested using the developed methods. The developed methods are sensitive and reliable, and can be used by diagnostic laboratories for routine testing and disease management decisions. PMID- 26850143 TI - Incidence of Lettuce mosaic virus in lettuce and its detection by polyclonal antibodies produced against recombinant coat protein expressed in Escherichia coli. AB - Lettuce mosaic virus (LMV), a member of the genus Potyvirus of family Potyviridae, causes mosaic disease in lettuce has recently been identified in India. The virus is seed borne and secondary infection occurs through aphids. To ensure virus freedom in seeds it is important to develop diagnostic tools, for serological methods the production of polyclonal antibodies is a prerequisite. The coat protein (CP) gene of LMV was amplified, cloned and expressed using pET 28a vector in Escherichia coli BL21DE3 competent cells. The LMV CP was expressed as a fusion protein containing a fragment of the E. coli His tag. The LMV CP/His protein reacted positively with a commercial antiserum against LMV in an immunoblot assay. Polyclonal antibodies purified from serum of rabbits immunized with the fusion protein gave positive results when LMV infected lettuce (Lactuca sativa) was tested at 1:1000 dilution in PTA-ELISA. These were used for specific detection of LMV in screening lettuce accessions. The efficacy of the raised polyclonal antiserum was high and it can be utilized in quarantine and clean seed production. PMID- 26850144 TI - The impact of comorbidities on inpatient Charcot neuroarthropathy cost and utilization. AB - AIMS: The purpose of this study was to portray the impact of comorbidities on inpatient cost and utilization in Charcot neuroarthropathy (CN) patients. METHODS: Two cohorts, CN and diabetic peripheral neuropathy (DPN), were identified by ICD-9 codes in the California Office for Statewide Health Planning and Development 2009-2012 public patient discharge files. DPN and CN costs and length of stay (LOS) were compared adjusting for the number of chronic conditions. The impact of the Elixhauser comorbidity measures and other comorbidities on costs and LOS in CN subjects was evaluated. RESULTS: CN was associated with 17.2% higher costs and 1.4 days longer LOS compared to DPN alone. Adjusting for 0.71 additional chronic conditions in CN patients accounted for 79.8% of variance and estimated a 13.9% cost difference between cohorts. Subjects averaged 4.5 Elixhauser comorbidities with higher scores corresponding to increased cost, LOS, and inpatient mortality. Other diabetic foot risk factors demonstrated that foot ulcers, foot infections, and osteomyelitis had significantly higher costs. Patients with foot ulcers, osteomyelitis, and depression had significantly increased LOS. CONCLUSIONS: Systemic and local comorbidities significantly impact the cost, utilization, and inpatient mortality in inpatient management of Charcot foot. PMID- 26850146 TI - Peptide-functionalized ZCIS QDs as fluorescent nanoprobe for targeted HER2 positive breast cancer cells imaging. AB - In this paper, the synthesis of alloyed CuInZnxS2+x quantum dots (ZCIS QDs), their transfer into aqueous solution via a polymer coating technique, and the use of these nanocrystals to selectively target HER2-positive cells, are reported. By optimizing first the ZnS shell deposition process onto the CuInS2 core, and next the encapsulation of the dots with the amphiphilic poly(maleic anhydride-alt-1 octadecene) (PMAO) polymer, water-dispersible ZCIS QDs were successfully prepared. The nanocrystals with a photoluminescence quantum yield of 35% were purified via centrifugation and ultracentrifugation and high quality nanoparticles with narrow size distributions and surface charges were obtained. After verifying the biocompatibility of PMO-coated ZCIS QDs, we coupled these nanocrystals with the LTVSPWY peptide and demonstrated via MTT assay that both bare and the peptide-linked QDs exhibit low cytotoxicity. The HER2-mediated delivery of the peptide-linked QDs was confirmed by confocal microscopy. This study indicates that as engineered QDs can efficiently be used as fluorescent nanoprobes for selective labelling of HER2-positive SKBR3 cancer cells. PMID- 26850145 TI - Increasing the strength and bioactivity of collagen scaffolds using customizable arrays of 3D-printed polymer fibers. AB - Tendon is a highly aligned connective tissue which transmits force from muscle to bone. Each year, people in the US sustain more than 32 million tendon injuries. To mitigate poor functional outcomes due to scar formation, current surgical techniques rely heavily on autografts. Biomaterial platforms and tissue engineering methods offer an alternative approach to address these injuries. Scaffolds incorporating aligned structural features can promote expansion of adult tenocytes and mesenchymal stem cells capable of tenogenic differentiation. However, appropriate balance between scaffold bioactivity and mechanical strength of these constructs remains challenging. The high porosity required to facilitate cell infiltration, nutrient and oxygen biotransport within three-dimensional constructs typically results in insufficient biomechanical strength. Here we describe the use of three-dimensional printing techniques to create customizable arrays of acrylonitrile butadiene styrene (ABS) fibers that can be incorporated into a collagen scaffold under development for tendon repair. Notably, mechanical performance of scaffold-fiber composites (elastic modulus, peak stress, strain at peak stress, and toughness) can be selectively manipulated by varying fiber reinforcement geometry without affecting the native bioactivity of the collagen scaffold. Further, we report an approach to functionalize ABS fibers with activity-inducing growth factors via sequential oxygen plasma and carbodiimide crosslinking treatments. Together, we report an adaptable approach to control both mechanical strength and presence of biomolecular cues in a manner orthogonal to the architecture of the collagen scaffold itself. STATEMENT OF SIGNIFICANCE: Tendon injuries account for more than 32 million injuries each year in the US alone. Current techniques use allografts to mitigate poor functional outcomes, but are not ideal platforms to induce functional regeneration following injury. Tissue engineering approaches using biomaterial substrates have significant potential for addressing these defects. However, the high porosity required to facilitate cell infiltration and nutrient transport often dictates that the resultant biomaterials has insufficient biomechanical strength. Here we describe the use of three-dimensional printing techniques to generate customizable fiber arrays from ABS polymer that can be incorporated into a collagen scaffold under development for tendon repair applications. Notably, the mechanical performance of the fiber-scaffold composite can be defined by the fiber array independent of the bioactivity of the collagen scaffold design. Further, the fiber array provides a substrate for growth factor delivery to aid healing. PMID- 26850147 TI - Brain biocompatibility and microglia response towards engineered self-assembling (RADA)4 nanoscaffolds. AB - (RADA)4-based nanoscaffolds have many inherent properties making them amenable to tissue engineering applications: ease of synthesis, ease of customization with bioactive moieties, and amenable for in situ nanoscaffold formation. There is a dearth in the literature on their biocompatibility in brain tissues; where the glia response is key to regulating the local host response. Herein, nanoscaffolds composed of (RADA)4 and (RADA)4-IKVAV mixtures were evaluated in terms of their effect on primary microglia in culture and general tissue (in vivo) biocompatibility (astrocyte and migroglia). Laminin-derived IKVAV peptide was chosen to promote beneficial cell interaction and attenuate deleterious glial responses. Microglia remained ramified when cultured with these nanoscaffolds, as observed using TNF-alpha and IL-1beta, NO, and proliferation assays. Evidence suggests that cultured microglia phagocytise the matrix whilst remaining ramified and viable, as shown visually and metabolically (MTT). Nanoscaffold intracerebral injection did not lead to microglia migration or proliferation, nor were glial scarring and axonal injury observed over the course of this study. IKVAV had no affect on microglia activation and astrogliosis. (RADA)4 should be advantageous for localized injection as a tuneable-platform device, which may be readily cleared without deleterious effects on tissue-resident microglia. STATEMENT OF SIGNIFICANCE: Self-assembling nanoscaffolds have many inherent properties making them amenable to tissue engineering applications: ease of synthesis, ease of customization with bioactive moieties, and amenable for in situ nanoscaffold formation. A dearth of literature exists on their biocompatibility in brain tissues; where the glia response is key to regulating the local host response. Herein, nanoscaffolds composed of the peptides (RADA)4 and (RADA)4-IKVAV mixtures were evaluated in terms of their effect on microglia cells in culture and general tissue (in vivo) biocompatibility (astrocyte and migroglia). Laminin-derived IKVAV peptide was chosen to promote beneficial cell interaction and attenuate deleterious glial responses. (RADA)4 nanoscaffolds showed no adverse effect from these cell types and should be advantageous for localized injection as a tuneable platform device. PMID- 26850148 TI - A mussel-inspired double-crosslinked tissue adhesive intended for internal medical use. AB - It has been a great challenge to develop aldehyde-free tissue adhesives that can function rapidly and controllably on wet internal tissues with fine adhesion strength, sound biocompatibility and degradability. To this end, we have devised a mussel-inspired easy-to-use double-crosslink tissue adhesive (DCTA) comprising a dopamine-conjugated gelatin macromer, a rapid crosslinker (namely, Fe(3+)), and a long-term acting crosslinker (namely, genipin). As a mussel-inspired gluing macromer, dopamine is grafted onto gelatin backbone via an one-step reaction, the catechol groups of which are capable of performing strong wet adhesion on tissue surfaces. By addition of genipin and Fe(3+), the formation of catechol-Fe(3+) complexation and accompanying spontaneous curing of genipin-primed covalent crosslinking of gluing macromers in one pot endows DCTA with the double-crosslink adhesion mechanism. Namely, the reversible catechol-Fe(3+) crosslinking executes an controllable and instant adhesive curing; while genipin-induced stable covalent crosslinking promises it with long-term effectiveness. This novel DCTA exhibits significantly higher wet tissue adhesion capability than the commercially available fibrin glue when applied on wet porcine skin and cartilage. In addition, this DCTA also demonstrates fine elasticity, sound biodegradability, and biocompatibility when contacting in vitro cultured cells and blood. In vivo biocompatibility and biodegradability are checked and confirmed via trials of subcutaneous implantation in nude mice model. This newly developed DCTA may be a highly promising product as a biological glue for internal medical use including internal tissue adhesion, sealing, and hemostasis. STATEMENT OF SIGNIFICANCE: There is a great demand for ideal tissue adhesives that can be widely used in gluing wet internal tissues. Here, we have devised a mussel-inspired easy-to-use double-crosslink tissue adhesive (DCTA) that meets the conditions as an ideal tissue adhesive. It is composed of gelatin-dopamine conjugates - a gluing macromer, Fe(3+) - a rapid crosslinker, and genipin - a long-term acting crosslinker. This DCTA is constructed with a novel complexation covalent double-crosslinking principle in one pot, in which the catechol-Fe(3+) crosslinking executes a controllable and instant adhesive curing, at the same time, genipin-induced covalent crosslinking promises it with long-term effectiveness in physiology conditions. This novel DCTA, with excellent wet tissue adhesion capability, fine elasticity, sound biodegradability, and biocompatibility, is a promising biological glue for internal medical use in surgical operations. PMID- 26850149 TI - Mitochondrial ORF79 levels determine pollen abortion in cytoplasmic male sterile rice. AB - Cytoplasmic male sterility (CMS) is an important agricultural trait characterized by lack of functional pollen, and caused by ectopic and defective mitochondrial gene expression. The pollen function in CMS plants is restored by the presence of nuclear-encoded restorer of fertility (Rf) genes. Previously, we cloned Rf2, which restores the fertility of Lead Rice (LD)-type CMS rice. However, neither the function of Rf2 nor the identity of the mitochondrial gene causing CMS has been determined in LD-CMS rice. Here, we show that the mitochondrial gene orf79 acts as a CMS-associated gene in LD-CMS rice, similar to its role in BT-CMS rice originating from Chinsurah Boro II, and Rf2 weakly restores fertility in BT-CMS rice. We also show that RF2 promotes degradation of atp6-orf79 RNA in a different manner from that of RF1, which is the Rf gene product in BT-CMS rice. The amount of ORF79 protein in LD-CMS rice was one-twentieth of the amount in BT-CMS rice. The difference in ORF79 protein levels probably accounts for the mild and severe pollen defects in LD-CMS and BT-CMS rice, respectively. In the presence of Rf2, accumulation of ORF79 was reduced to almost zero and 25% in LD-CMS and BT-CMS rice, respectively, which probably accounts for the complete and weak fertility restoration abilities of Rf2 in LD-CMS and BT-CMS rice, respectively. These observations indicate that the amount of ORF79 influences the pollen fertility in two strains of rice in which CMS is induced by orf79. PMID- 26850150 TI - [Gonococcal ophthalmia neonatorum: Clinical illustration, prevention, and future prospects]. AB - A 6-day-old infant presented with a bilateral suppurative ocular discharge with a conjunctival erythema. Polymerase chain reaction was performed on the pus and showed the presence of Neisseria gonorrhoeae DNA. Therapy with intravenous cefotaxime was initiated and completed with local application of tobramycin. This infection was associated with a small unilateral corneal lesion, with rapid resolution. This case provides the opportunity to focus on newborn suppurative conjunctivitis and its treatment. The different prophylaxes available (silver nitrate, povidone-iodine, local antibiotics, etc.) and their respective advantages and disadvantages are reviewed. There is no clear consensus on the most effective solution. Additionally, universal prophylaxis is challenged in several countries, where it is no longer recommended. PMID- 26850151 TI - [Prenatal discovery of Joubert syndrome associated with small bowel volvulus]. AB - Joubert syndrome and prenatal volvulus are difficult to diagnose during pregnancy. Joubert syndrome and related diseases should be considered in case of prenatal abnormal features of the fourth ventricle. Small bowel volvulus is also a surgical emergency because of the risk of intestinal necrosis before or after delivery. This type of condition justifies the transfer of pregnant women to a specialized hospital where the newborn may receive appropriate care. We report the case of a 31-week and 4-day gestational-age fetus in whom intrauterine growth retardation and small-bowel volvulus were diagnosed. Additional imaging revealed associated Joubert syndrome. This highlights the need for regular ultrasound monitoring during pregnancy and the comanagement of obstetricians and pediatricians to provide appropriate care before and after delivery. PMID- 26850152 TI - [Congenital mucocele of the ventral face of the tongue]. AB - BACKGROUND: Congenital cystic lesions of the oral cavity are an extremely rare occurrence. Their prenatal diagnosis is essential since they can impede respiratory and swallowing functions. We describe a case that was detected prenatally and discuss its management. CASE REPORT: A 21-year-old primigravida patient who was 23 weeks pregnant was referred to our obstetrics and gynecology center after fetal ultrasonography showed a cystic lesion of the oral cavity. She had no family history of any congenital anomalies. Ultrasonography showed a male fetus with an anechoic mass measuring 21*11 mm encompassing the entire oral cavity, evoking either a mucocele or a cystic hygroma. Magnetic resonance imaging (MRI) showed a fetus with a wide-open mouth, due to a well-demarcated protruding cystic mass with no solid component, suggestive of a mucocele. A prenatal sonographically guided percutaneous needle aspiration of mucous fluid was performed at 33 gestational weeks. Although the mucocele decreased significantly in size, it nevertheless continued to expand progressively. After an uncomplicated pregnancy, the patient had spontaneous onset of labor at 39 weeks of gestation. An iterative aspiration was performed in the same manner in utero, resulting in a complete collapse of the mucocele. If needed, intubation could be considered. A 3030-g male was born by vaginal delivery, without respiratory distress. Clinical examination showed the extremely opened mouth and confirmed the presence of a large cystic mass approximately 4 cm in diameter, of sublingual origin and encompassing the entire oral cavity. The continuous protrusion of the tongue was responsible for the infant's inability to close the mouth and be breastfed. After insertion of a feeding tube, the newborn had maxillofacial surgery consisting in marsupialization of the cyst at 2 days of age. The mucocele decreased in size and the postoperative course was uneventful. No recurrence was observed at 6 months' follow-up. DISCUSSION AND CONCLUSION: Congenital mucoceles of the tongue are very rare benign lesions of the oral cavity, resulting from extravasation or retention of mucus from minor salivary glands. Their prevalence is unknown and, to our knowledge, less than ten cases of prenatal diagnosis have been previously reported. Such cystic lesions can cause respiratory distress and swallowing disorders in newborns. They are usually suspected on ultrasonography. MRI highlights the nature of the lesion and its locoregional connections with muscles and blood vessels. It provides a good analysis of the soft tissues and can distinguish between the muscles of the tongue and the pathologic mass. However, the use of CT has been reported when the diagnosis was made after childbirth or in adulthood. Given the risks of interference of the lesion with respiratory and swallowing functions, intrauterine decompression of the mucocele can be an option to prevent respiratory distress at birth and the need for neonatal intubation. Mucoceles provide somewhat confusing and disturbing ultrasonographic appearances, which can be stressful for the medical team and parents. Prenatal diagnosis and early surgical intervention (marsupialization, complete excision of the cyst or the salivary gland) can prevent risks of breathing distress and breastfeeding problems. Therefore, this strategy is essential to offer fast and satisfactory management of this rare but anxiety producing congenital situation. PMID- 26850153 TI - [Neonatal cholestasis]. AB - "Cholestasis" means abnormal synthesis or secretion of bile. The main symptom in a neonate or infant is jaundice. Urine is dark, staining diapers, and stools are variably pale or white. Vitamin K should be injected (to prevent coagulation disorders due to malabsorption). The two diagnoses requiring urgent treatment are urinary tract infection and biliary atresia. If stools are permanently white, biliary atresia is highly probable. A few genetic causes of intrahepatic cholestasis should be screened and corrective surgery organized. The diseases responsible for cholestasis in this age group are described as well as the investigations and treatments, including the management of non-specific complications of cholestasis. A delay in the diagnosis of biliary atresia can have such severe consequences that consultation with a hepatology unit or transfer should be easy and rapid. PMID- 26850154 TI - [Respiratory outcome of bronchopulmonary dysplasia in school-age children]. AB - BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease of infancy. The influence of its initial severity on long-term respiratory outcome remains uncertain. OBJECTIVES: The purpose of this study was to examine the impact of "new BPD" on respiratory morbidity as well as respiratory function at rest and during exercise in school-age children. METHODS: The 93 preterm newborns (<33 weeks gestation) presenting with BPD between 1997 and 2004 at the Rennes University Hospital had been proposed for a specific follow-up program. The children included in this cohort and presenting without severe handicap or motor deficit were eligible for this observational retrospective study. Their standardized clinical evaluation and the results of the pulmonary function tests and cardiopulmonary exercise tests performed between the ages of 7 and 14 years were studied. BPD was considered to be moderate when respiratory or oxygen support continued at 36 weeks gestation with an FiO2 less than 30% and severe when FiO2 was greater than 30%. RESULTS: Among the 36 children assessed, the initial severity of the BPD was mild in 12 cases, moderate in 12 cases, and severe in 12 cases. The mean age at the time of the pulmonary function test (PFT) was 9.9 (+/-1.9) years, 19 children (53%) had respiratory symptoms during the year before the test, and six (17%) underwent long-term treatment. The PFT was abnormal for 32 children (89%): 23 showed airway obstruction, 16 hyperinflation, three increases in bronchial reactivity, and two restrictions. The residual volume/total lung capacity ratio was the only parameter related to the severity of BPD (P<0.05). The cardiopulmonary exercise test was given to 35 children: 15 of them had normal exercise ability but with a limited ventilatory reserve. CONCLUSIONS: Half of the children included in this "new-BPD" follow-up cohort had clinical respiratory morbidity and most of the children followed presented with persistent alterations in pulmonary function tests at school age, which were not associated with significant alterations in the maximum aerobic performance. PMID- 26850155 TI - [Malignant infantile osteopetrosis: Case report of a 5-month-old boy]. AB - Malignant infantile osteopetrosis is a rare congenital disease characterized by a dysfunction of osteoclasts followed by an abnormal bone densification. We report the case of a 5-month-old infant in whom this disease was suspected because of the clinical (hepatosplenomegaly, gingival hypertrophy), hematological (pancytopenia and hypocalcemia), and radiological criteria (abnormal bone density, periosteal reaction). The genetic investigation confirmed the diagnosis. Compound heterozygous mutations in the CLCN7 gene were identified, including an as yet undescribed mutation. The second mutation had already been described as being responsible for severe and irreversible neurological damage in patients with osteopetrosis. Since this patient presented severely delayed development, he was not eligible for bone marrow transplantation. PMID- 26850156 TI - Metagenomic profiles of antibiotic resistance genes in paddy soils from South China. AB - Overuse and arbitrary discarding of antibiotics have expanded antibiotic resistance reservoirs, from gut, waste water and activated sludge, to soil, freshwater and even the ocean. Based on the structured Antibiotic Resistance Genes Database and next generation sequencing, metagenomic analysis was used for the first time to detect and quantify antibiotic resistance genes (ARGs) in paddy soils from South China. A total of 16 types of ARGs were identified, corresponding to 110 ARG subtypes. The abundances and distribution pattern of ARGs in paddy soil were distinctively different from those in activated sludge and pristine deep ocean sediment, but close to those of sediment from human impacted estuaries. Multidrug resistance genes were the most dominant type (38 47.5%) in all samples, and the ARGs detected encompassed the three major resistance mechanisms, among which extrusion by efflux pumps was predominant. Redundancy analysis (RDA) showed that pH was significantly correlated with the distribution of ARG subtypes (P < 0.05). Our results provided a broad spectrum profile of ARGs in paddy soil, indicating that ARGs are widespread in paddy soils of South China. PMID- 26850157 TI - Evidence for plasmid-mediated salt tolerance in the human gut microbiome and potential mechanisms. AB - The human gut microbiome is critical to health and wellbeing. It hosts a complex ecosystem comprising a multitude of bacterial species, which contributes functionality that would otherwise be absent from the host. Transient and commensal bacteria in the gut must withstand many stresses. The influence of mobile genetic elements such as plasmids in stress adaptation within the ecosystem is poorly understood. Using a mobilomic approach we found evidence for plasmid-mediated osmotolerance as a phenotype amongst the Proteobacteria in healthy faecal slurries. A transconjugant carrying multiple plasmids acquired from healthy faecal slurry demonstrated increased osmotolerance in the presence of metal salts, particularly potassium chloride, which was not evident in the recipient. Pyrosequencing and analysis of the total plasmid DNA demonstrated the presence of plasmid-borne osmotolerance systems (including KdpD and H-NS) which may be linked to the observed phenotype. This is the first report of a transferable osmotolerance phenotype in gut commensals and may have implications for the transfer of osmotolerance in other niches. PMID- 26850158 TI - Mycorrhizal fungal communities respond to experimental elevation of soil pH and P availability in temperate hardwood forests. AB - Many forests are affected by chronic acid deposition, which can lower soil pH and limit the availability of nutrients such as phosphorus (P), but the response of mycorrhizal fungi to changes in soil pH and P availability and how this affects tree acquisition of nutrients is not well understood. Here, we describe an ecosystem-level manipulation in 72 plots, which increased pH and/or P availability across six forests in Ohio, USA. Two years after treatment initiation, mycorrhizal fungi on roots were examined with molecular techniques, including 454-pyrosequencing. Elevating pH significantly increased arbuscular mycorrhizal (AM) fungal colonization and total fungal biomass, and affected community structure of AM and ectomycorrhizal (EcM) fungi, suggesting that raising soil pH altered both mycorrhizal fungal communities and fungal growth. AM fungal taxa were generally negatively correlated with recalcitrant P pools and soil enzyme activity, whereas EcM fungal taxa displayed variable responses, suggesting that these groups respond differently to P availability. Additionally, the production of extracellular phosphatase enzymes in soil decreased under elevated pH, suggesting a shift in functional activity of soil microbes with pH alteration. Thus, our findings suggest that elevating pH increased soil P availability, which may partly underlie the mycorrhizal fungal responses we observed. PMID- 26850159 TI - Soil bacterial communities associated with natural and commercial Cyclopia spp. AB - The commercially important plants in the genus Cyclopia spp. are indigenous to the Cape Floristic Region of South Africa and are used to manufacture an herbal tea known as honeybush tea. Growing in the low nutrient fynbos soils, these plants are highly dependent on symbiotic interactions with soil microorganisms for nutrient acquisition. The aim of this study was to investigate the soil bacterial communities associated with two commercially important Cyclopia species, namely C. subternata and C. longifolia. Specific interest was the differences between rhizosphere and bulk soil collected from natural sites and commercially grown plants. Samples were collected on two occasions to include a dry summer and wet winter season. Results showed that the dominant bacterial taxa associated with these plants included Acidobacteria, Actinobacteria, Bacteroidetes and Proteobacteria. Commercial and natural as well as rhizosphere and bulk soil samples were highly similar in bacterial diversity and species richness. Significant differences were detected in bacterial community structures and co-occurrence patterns between the wet and dry seasons. The results of this study improved our knowledge on what effect commercial Cyclopia plantations and seasonal changes can have on soil bacterial communities within the endemic fynbos biome. PMID- 26850160 TI - Shift in antibiotic resistance gene profiles associated with nanosilver during wastewater treatment. AB - This study investigated the response of antibiotic resistance genes (ARGs) to nanosilver (Ag) in lab-scale nitrifying sequencing batch reactors (SBRs), compared to Ag(+)-dosed and undosed controls. Quantitative polymerase chain reaction (q-PCR) targeting sul1, tet(O), ermB and the class I integron gene intI1 and corresponding RNA expression did not indicate measureable effects of nanoAg or Ag(+) on abundance or expression of these genes. However, high-throughput sequencing based metagenomic analysis provided a much broader profile of gene responses and revealed a greater abundance of aminoglycoside resistance genes (mainly strA) in reactors dosed with nanoAg. In contrast, bacitracin and macrolide-lincosamide-streptogramin (MLS) resistance genes were more abundant in the SBRs dosed with Ag(+). The distinct ARG profiles associated with nanoAg and Ag(+) were correlated with the taxonomic composition of the microbial communities. This study indicates that nanoAg may interact with bacteria differently from Ag(+) during biological wastewater treatment. Therefore, it cannot necessarily be assumed that nanosilver behaves identically as Ag(+) when conducting a risk assessment for release into the environment. PMID- 26850161 TI - Multidrug resistant, extended spectrum beta-lactamase (ESBL)-producing Escherichia coli isolated from a dairy farm. AB - Escherichia coli strains were isolated from a single dairy farm as a sentinel organism for the persistence of antibiotic resistance genes in the farm environment. Selective microbiological media were used to obtain 126 E. coli isolates from slurry and faeces samples from different farm areas. Antibiotic resistance profiling for 17 antibiotics (seven antibiotic classes) showed 57.9% of the isolates were resistant to between 3 and 15 antibiotics. The highest frequency of resistance was to ampicillin (56.3%), and the lowest to imipenem (1.6%), which appeared to be an unstable phenotype and was subsequently lost. Extended spectrum beta-lactamase (ESBL) resistance was detected in 53 isolates and blaCTX-M, blaTEM and blaOXA genes were detected by PCR in 12, 4 and 2 strains, respectively. Phenotypically most isolates showing resistance to cephalosporins were AmpC rather than ESBL, a number of isolates having both activities. Phenotypic resistance patterns suggested co-acquisition of some resistance genes within subsets of the isolates. Genotyping using ERIC-PCR demonstrated these were not clonal, and therefore co-resistance may be associated with mobile genetic elements. These data show a snapshot of diverse resistance genes present in the E. coli population reservoir, including resistance to historically used antibiotics as well as cephalosporins in contemporary use. PMID- 26850163 TI - Learning dynamics for systems with space structure: Comment on the paper "Collective learning modeling based on the kinetic theory of active particles" by D. Burini et al. PMID- 26850164 TI - Two possible driving forces supporting the evolution of animal communication: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26850162 TI - Antimicrobial resistance dashboard application for mapping environmental occurrence and resistant pathogens. AB - An antibiotic resistance (AR) Dashboard application is being developed regarding the occurrence of antibiotic resistance genes (ARG) and bacteria (ARB) in environmental and clinical settings. The application gathers and geospatially maps AR studies, reported occurrence and antibiograms, which can be downloaded for offline analysis. With the integration of multiple data sets, the database can be used on a regional or global scale to identify hot spots for ARGs and ARB; track and link spread and transmission, quantify environmental or human factors influencing presence and persistence of ARG harboring organisms; differentiate natural ARGs from those distributed via human or animal activity; cluster and compare ARGs connections in different environments and hosts; and identify genes that can be used as proxies to routinely monitor anthropogenic pollution. To initially populate and develop the AR Dashboard, a qPCR ARG array was tested with 30 surface waters, primary influent from three waste water treatment facilities, ten clinical isolates from a regional hospital and data from previously published studies including river, park soil and swine farm samples. Interested users are invited to download a beta version (available on iOS or Android), submit AR information using the application, and provide feedback on current and prospective functionalities. PMID- 26850165 TI - The emergence of grammar in a language-ready brain: Comment on "Towards a Computational Comparative Neuroprimatology: Framing the language-ready brain" by Michael A. Arbib. PMID- 26850166 TI - pophelper: an R package and web app to analyse and visualize population structure. AB - The pophelper r package and web app are software tools to aid in population structure analyses. They can be used for the analyses and visualization of output generated from population assignment programs such as admixture, structure and tess. Some of the functions include parsing output run files to tabulate data, estimating K using the Evanno method, generating files for clumpp and functionality to create barplots. These functions can be streamlined into standard r analysis workflows. The latest version of the package is available on github (https://github.com/royfrancis/pophelper). An interactive web version of the pophelper package is available which covers the same functionalities as the r package version with features such as interactive plots, cluster alignment during plotting, sorting individuals and ordering of population groups. The interactive version is available at http://pophelper.com/. PMID- 26850167 TI - Structure of wild type and mutant F508del CFTR: A small-angle X-ray scattering study of the protein-detergent complexes. AB - CFTR is an anionic channel expressed in epithelia whose mutations cause cystic fibrosis. Wild (WT) and mutated (F508del) types were over-expressed in yeast, solubilised in the detergent LPG-14 and purified. The detergent-CFTR complexes were studied by SAXS techniques using a solvent of variable density. The final result of the study is the numerical value of a set of parameters: molecular mass, volume and radius of gyration, average electron density and second moment of the electron density fluctuations inside the particles. It is also shown that in the complex the centres of gravity of CFTR and of the detergent are displaced relative to each other. The analysis of these parameters led to the determination of the size and shape of the volumes occupied by protein and by detergent in the complex. WT-CFTR to be an elongated molecule (maximum diameter ~12.4nm) which spans a flat detergent micelle. The distance distribution function, P(r) confirms that the WT-CFTR is elongated and with an inhomogeneous electronic density. The F508del-CFTR molecule is also elongated (maximum diameter ~13.2nm), but the associated detergent micelle hides a larger surface, plausibly related to an increased exposure of hydrophobic portions of the mutated protein. The corresponding P(r) is consistent with the presence of well defined domains, probably linked by flexible regions. These differences suggest that the full length mutant F508del-CFTR has a detectably different conformation, in contrast to the minor differences observed for the isolated F508-containing domain. We interpret the data in terms of an incomplete post-translational assembly of the protein domains. PMID- 26850168 TI - Helicobacter pylori cell binding factor 2: Insights into domain motion. AB - Helicobacter pylori cell binding factor 2 (HpCBF2) is an antigenic virulence factor belonging to the SurA-like peptidyl-prolyl cis-trans isomerase family with implications for pathogenicity in the human gastrointestinal tract. HpCBF2 possesses PPIase activity and could act as a periplasmic chaperone to regulate outer membrane protein assembly. Here, we measured the isomerization and chaperone activity of HpCBF2, and determined the crystal structure of HpCBF2 in complex with an inhibitor, indole-2-carboxylic acid (I2CA), at 2.4A resolution. HpCBF2-I2CA forms a homodimer encasing a large central hydrophobic cavity with a basket-like structure, and each monomer contains a PPIase and a chaperone domain. In the HpCBF2-I2CA dimer, the two PPIase domains separate by a distance of 22.8A, while the two chaperone domains arrange in a domain-swap manner. The PPIase domains bound with I2CA ligand face towards the chaperone domains and are shielded by surrounding hydrophobic residues. With the aid of SAXS experiments, we also revealed domain motion between the apo- and I2CA-bound states of HpCBF2. The domain motion in HpCBF2 might be necessary for the isomerization activity of PPIase and the accommodation of the unfolded and partially folded peptides to refold by chaperone domain. PMID- 26850169 TI - Structural characterization of GASDALIE Fc bound to the activating Fc receptor FcgammaRIIIa. AB - The Fc region of Immunoglobulin G (IgG) initiates inflammatory responses such as antibody-dependent cell-mediated cytotoxicity (ADCC) through binding to activating Fc receptors (FcgammaRI, FcgammaRIIa, FcgammaRIIIa). These receptors are expressed on the surface of immune cells including macrophages, dendritic cells, and natural killer cells. An inhibitory receptor, FcgammaRIIb, is expressed on macrophages and other myeloid leukocytes simultaneously with the activating receptor FcgammaRIIa, thereby setting a threshold for cell activation. The affinity of IgG Fc for binding activating Fc receptors depends on IgG subclass and the composition of N-linked glycans attached to a conserved asparagine in the Fc CH2 domain. For example, Fc regions with afucosylated glycans bind more tightly to FcgammaRIIIa than fucosylated Fc, and afucosylated Fcs exhibit enhanced ADCC activity in vivo and in vitro. Enhanced pro inflammatory responses have also been seen for Fc regions with amino acid substitutions. GASDALIE Fc is an Fc mutant (G236A/S239D/A330L/I332E) that exhibits a higher affinity for FcgammaRIIIa and increased effector functions in vivo compared to wild-type Fc. To explore its altered functions, we compared the affinities of GASDALIE and wild-type Fc for activating and inhibitory FcgammaRs. We also determined the crystal structure of GASDALIE Fc alone and bound to FcgammaRIIIa. The overall structure of GASDALIE Fc alone was similar to wild-type Fc structures, however, increased electrostatic interactions in the GASDALIE Fc:FcgammaRIIIa interface compared with other Fc:FcgammaR structures suggest a mechanism for the increased affinity of GASDALIE Fc for FcgammaRIIIa. PMID- 26850171 TI - Quantification of systemic right ventricle by echocardiography. AB - Improvements in cardiac imaging have recently focused a great interest on the right ventricle (RV). In patients with congenital heart disease, the right ventricle (RV) may support the systemic circulation (systemic RV). There are 2 different anatomic conditions providing such physiology: the congenitally corrected transposition of the great arteries (ccTGA) and the TGA surgically corrected by atrial switch. During the last decades, evidence is accumulating that progressive systemic RV failure develops leading to considerable morbidity and mortality. Various imaging modalities have been used to evaluate the systemic RV, but echocardiography is still predominantly used in clinical practice, allowing an anatomic and functional approach of the systemic RV function and the potential associated anomalies. The goal of this review is to offer a clinical perspective of the non-invasive evaluation of the systemic RV by echocardiography. PMID- 26850170 TI - Easy mammalian expression and crystallography of maltose-binding protein-fused human proteins. AB - We present a strategy to obtain milligrams of highly post-translationally modified eukaryotic proteins, transiently expressed in mammalian cells as rigid or cleavable fusions with a mammalianized version of bacterial maltose-binding protein (mMBP). This variant was engineered to combine mutations that enhance MBP solubility and affinity purification, as well as provide crystal-packing interactions for increased crystallizability. Using this cell type-independent approach, we could increase the expression of secreted and intracellular human proteins up to 200-fold. By molecular replacement with MBP, we readily determined five novel high-resolution structures of rigid fusions of targets that otherwise defied crystallization. PMID- 26850172 TI - What level of pain are patients happy to live with after surgery for lumbar degenerative disorders? AB - BACKGROUND CONTEXT: A new approach to the interpretation of treatment success comprises the reporting of the proportion of patients whose symptoms have reduced to an acceptable level, ie, who have reached a satisfactory state. PURPOSE: We sought to evaluate the acceptable level of pain in patients after surgery for painful degenerative lumbar disorders. DESIGN: This is a cross-sectional study of outcome data, 12 months postoperatively. PATIENT SAMPLE: The sample includes 6,943 patients registered in our in-house Spine Outcomes Registry, nested within the EUROSPINE "Spine Tango" registry, undergoing surgery for degenerative disorders of the lumbar spine (disc herniation [DH; N=1,608], spinal stenosis [SS; N=1,782], degenerative spondylolisthesis [DS; N=1,000], degenerative deformity [DegDef; N=612], and degenerative disc or segment disease [DegSeg; N=473], and 1,468 degenerative but no specific category). OUTCOME MEASURES: The Core Outcome Measures Index (COMI) was the outcome measure. The specific items used for this analysis were the two 0 to 10 graphic rating scales for back and leg pain and the symptom-specific well-being (SSWB) item "if you had to spend the rest of your life with the symptoms you have now, how would you feel about it?", with a 5-point response scale from "very satisfied" to "very dissatisfied." METHODS: The COMI was completed before and at 3, 12, and 24 months after surgery. Answers on the SSWB were dichotomized and used as the external criterion in receiver operating characteristics (ROC) analysis to derive the cutoff score for pain (the higher of back and leg pain) indicating being at least "somewhat satisfied" with the symptom state 12 months postoperatively. Sensitivity analyses were carried out for various subgroups (sex, age, pathology, comorbidity status, smoking status, preoperative pain level, previous surgery, type of health insurance, and time of follow-up [3 and 24 months]). The study was funded by the Schulthess Klinik Research Funds; there were no potential conflict of interest associated biases for any of the authors. RESULTS: Of 6,943 patients, 6,248 (90%) returned a 12-month questionnaire, of which 47% reported being at least somewhat satisfied with their symptom state (52% [DH], 45% [SS], 53% [DS], 44% [DegDef], 45% [DegSeg], and 44% [others]). The areas under the curve for the ROCs were 0.89 to 0.91 for the different pathologies, indicating a good ability of the pain score to discriminate between being in a satisfactory state or not. The cutoff indicating a satisfactory symptom state was <=2 points for DH (sensitivity: 76%; specificity: 88%) and <=3 points for all other pathologies (sensitivity: 79%-84%; specificity 81%-85%). The sensitivity analyses revealed <=3 points to be the most common cutoff for the various subgroups. CONCLUSIONS: Most spine interventions decrease pain but rarely do they totally eliminate it. Reporting of the percent of patients achieving a pain score equivalent to the "acceptable symptom state" may represent a more stringent target for denoting surgical success in the treatment of painful spinal disorders. For DH, this is <=2, and for other degenerative pathologies it is <=3. PMID- 26850173 TI - Anterior transcorporeal approach of percutaneous endoscopic cervical discectomy for disc herniation at the C4-C5 levels: a technical note. AB - BACKGROUND CONTEXT: With the continuous development of the spinal endoscopic technique in recent years, percutaneous endoscopic cervical discectomy (PECD) has emerged, which bridges the gap between conservative therapy and traditional surgery and has been mainly divided into the anterior transdiscal approach and the posterior interlaminar access. Because of the relatively greater violation to the anterior nucleus pulposus, there is a higher potential of postoperative intervertebral space decrease in the anterior transdiscal approach than in the posterior interlaminar access. In addition, when the herniated lesion is migrated upward or downward behind the vertebral body, both approaches, and even anterior cervical discectomy and fusion, are impractical, and corpectomy is commonly considered as the only efficacious treatment. Anterior transcorporeal approach under endoscopy could enable an individual and adjustable trajectory within the vertebral body under different conditions of disc herniation preserving the motion of adjacent segment, especially in a migrated or sequestered lesion. PURPOSE: This report aimed to first describe a novel anterior transcorporeal approach under endoscopy in which we addressed a migrated disc herniation at the C4-C5 levels. STUDY DESIGN: A technical report was carried out. PATIENT SAMPLE: A 37-year-old woman presented with posterior neck pain and weakness of extremities for 9 months. On neurologic examination, tingling sensation and numbness were not obvious. However, the power of extremities was dramatically decreased at a level of 3. Hoffmann sign was positive in the bilateral hand. Magnetic resonance imaging (MRI) showed a huge herniation of the C4-C5 disc compressing the median area of the spinal cord. Besides the C4-C5 disc herniation, preoperative computer tomography (CT) also detected that the herniated disc had partial calcification. A novel anterior transcorporeal approach of PECD, through the vertebral body of C5, was performed to address a migrated disc herniation at the C4-C5 levels. OUTCOME MEASURES: The posterior neck pain was measured using the visual analog scale (VAS). METHODS: A novel anterior transcorporeal approach under endoscopy was performed to address a migrated disc herniation at the C4-C5 levels. RESULTS: This operation was accomplished in 75 minutes. Postoperatively, the drainage tube was retained into the drilling hole for 24 hours to avoid the possibility of hematoma. The patient was advised to wear a neck collar for 3 weeks. Immediately after the operation, the posterior neck pain improved from VAS 7/10 preoperatively to 3/10, and the myodynamia of extremities improved stepwise. At 12 hours postoperatively, the range of motion was also improved. In the further follow-up, the patient has completely recovered from the preoperative symptoms, whose myodynamia of extremities is normal. Besides the postoperative MRI, a total removal of the herniated disc and the transcorporeal drilling tunnel are observed in CT. At postoperative 3-month follow-up, neither disc space narrowing nor instability was observed on CT, in which the bone defect after drilling tunnelwas partially decreased, indicating bone healing. There were no surgery-related complications, such as dysphagia, Horner syndrome, recurrent laryngeal nerve palsy, vagus nerve injury, tracheoesophageal injury, or cervical hematocele. CONCLUSIONS: As a supplement to the described surgical approach of PECD, the transcorporeal approach is a novel access for the treatment of cervical intervertebral disc herniation. Among the advantages of this approach are providing a clear visual field during microendoscopic surgery and decreasing the intraoperative iatrogenic injury to, as well as avoiding violation to the discal tissue. Theoretically, the potential of secondary decline of intervertebral height is low. However, as the limitation of one case shows, whether this transcorporeal approach is efficacious and reliable should be verified in a further comparative cohort study with a large volume of patients. PMID- 26850174 TI - Zinc has insulin-mimetic properties which enhance spinal fusion in a rat model. AB - BACKGROUND CONTEXT: Previous studies have found that insulin or insulin-like growth factor treatment can stimulate fracture healing in diabetic and normal animal models, and increase fusion rates in a rat spinal fusion model. Insulin mimetic agents, such as zinc, have demonstrated antidiabetic effects in animal and human studies, and these agents that mimic the effects of insulin could produce the same beneficial effects on bone regeneration and spinal fusion. PURPOSE: The purpose of this study was to analyze the effects of locally applied zinc on spinal fusion in a rat model. STUDY DESIGN/SETTING: Institutional Animal Care and Use Committee-approved animal study using Sprague-Dawley rats was used as the study design. METHODS: Thirty Sprague-Dawley rats (450-500 g) underwent L4 L5 posterolateral lumbar fusion (PLF). After decortication and application of approximately 0.3 g of autograft per side, one of three pellets were added to each site: high-dose zinc calcium sulfate (ZnCaSO4), low-dose ZnCaSO4 (half of the high dose), or a control palmitic acid pellet (no Zn dose). Systemic blood glucose levels were measured 24 hours postoperatively. Rats were sacrificed after 8weeks and the PLFs analyzed qualitatively by manual palpation and radiograph review, and quantitatively by micro-computed tomography (CT) analysis of bone volume and trabecular thickness. Statistical analyses with p-values set at .05 were accomplished with analysis of variance, followed by posthoc tests for quantitative data, or Mann-Whitney rank tests for qualitative assessments. RESULTS: Compared with controls, the low-dose zinc group demonstrated a significantly higher manual palpation grade (p=.011), radiographic score (p=.045), and bone formation on micro-CT (172.9 mm(3) vs. 126.7 mm(3) for controls) (p<.01). The high-dose zinc also demonstrated a significantly higher radiographic score (p=.017) and bone formation on micro-CT (172.7 mm(3) vs. 126.7 mm(3)) (p<.01) versus controls, and was trending toward higher manual palpation scores (p=.058). CONCLUSIONS: This study demonstrates the potential benefit of a locally applied insulin-mimetic agent, such as zinc, in a rat lumbar fusion model. Previous studies have demonstrated the benefits of local insulin application in the same model, and it appears that zinc has similar effects. PMID- 26850175 TI - Do magnetic growing rods have lower complication rates compared with conventional growing rods? AB - BACKGROUND CONTEXT: The main advantage cited for the use of the magnetic controlled growing rod (MCGR) system over the conventional growing rod (CGR) in early-onset scoliosis is avoiding repeated invasive surgical procedures for lengthening, thus reducing, complications. PURPOSE: The study aimed to evaluate the complications of the MCGR system against the CGR system in our center. STUDY DESIGN/SETTING: This is a retrospective case control series. PATIENT SAMPLE: The sample includes patients with early-onset scoliosis treated with MCGR or CGR. OUTCOME MEASURES: Complications and unplanned return to theater were the outcome measures. RESULTS: Of the 37 patients (MCGR, N=10; CGR, N=27) in our cohort, 28 patients (76%) had at least one complication. Taking into account the follow-up period, MCGR had a higher complication rate than CGR group (0.32 complication per patient per year vs. 0.15 complication per patient per year). The use of MCGR was associated with a lower risk of deep infection (odds ratio [OR]: 0.22; p=.22) and superficial infection (OR: 0.07, p=.017) but increased risk of metalwork problems (OR: 4.67; p=.045) and unplanned return to theater (OR: 2.92; p=.05) compared with CGR. CONCLUSIONS: Although MCGR has a lower rate of both deep and superficial infections when compared with CGR, it does not completely avoid repeated invasive surgical procedures as previously suggested. It does have a significant increased risk of metalwork problems and unplanned return to theater. PMID- 26850176 TI - Myopic Maculopathy and Optic Disc Changes in Highly Myopic Young Asian Eyes and Impact on Visual Acuity. AB - PURPOSE: To determine the prevalence and risk factors of myopic maculopathy and specific optic disc and macular changes in highly myopic eyes of young Asian adults and their impact on visual acuity. DESIGN: Prospective cross-sectional study. METHODS: In total, 593 highly myopic (spherical equivalent refraction [SER] less than -6.00 diopters [D]) and 156 emmetropic (SER between -1.00 and +1.00 D) male participants from a population-based survey were included. All participants underwent standardized medical interviews, ophthalmic examination, and color fundus photographs. These photographs were graded systematically to determine the presence of optic disc and macular lesions. Myopic maculopathy was classified based on the International Classification of Myopic Maculopathy. RESULTS: The mean age was 21.1 +/- 1.2 years. The mean SER for the highly myopic and emmetropic group was -8.87 +/- 2.11 D and 0.40 +/- 0.39 D, respectively (P < .001). Compared to emmetropic eyes, highly myopic eyes were significantly more likely to have optic disc tilt, peripapillary atrophy (PPA), posterior staphyloma, chorioretinal atrophy, and myopic maculopathy (all P < .001). The main findings included PPA (98.3%), disc tilt (22.0%), posterior staphyloma (32.0%), and chorioretinal atrophy (8.3%). Myopic maculopathy was present in 8.3% of highly myopic eyes and was associated with older age (odds ratio [OR] 1.66; 95% CI: 1.22, 2.26), reduced choroidal thickness (OR 0.99; 95% CI: 0.98, 0.99), and increased axial length (AL) (OR 1.52; 95% CI: 1.06, 2.19). The presence of disc tilt, posterior staphyloma, and chorioretinal atrophy were associated with reduced visual acuity. CONCLUSIONS: Our study showed that myopia-related changes of the optic disc and macula were common in highly myopic eyes even at a young age. The risk factors for myopic maculopathy include increased age, longer AL, and reduced choroidal thickness. Some of these changes were associated with reduced central visual function. PMID- 26850177 TI - Sitting and chronic disease: where do we go from here? PMID- 26850178 TI - Septum-based cervical lymph-node free flap in rat: a new model. AB - BACKGROUND: A limited number of lymph node flap models are available in rats, and none of them include a skin paddle. The aim of this study was to describe a new cervical lymph node-adipo-cutaneous flap model in the rat for future experimental studies. MATERIAL AND METHODS: Fifteen Wistar rats were used. In four, neck anatomy was investigated with special focus on cervical lymph nodes. In eleven rats, a lymph node flap with a skin paddle of 1.5 * 0.5 cm centered along the surface projection of the innominate septum was harvested and transferred to the inguinal region. The rats were followed-up for 7 d. At 30-d postoperatively, the lymphatic flow restoration with the recipient limb lymphatics was assessed with methylene blue, and histology was performed on excised flaps. RESULTS: According to the anatomic findings, the flap was based on an innominate septum which was a well-defined adipofascial structure containing glandular vessels to the surrounding tissues and located between submandibular-sublingual glandular complex and parotid gland. Flap's microvascular and lymph node anatomy (two to three lymph nodes) was constant. Donor-site morbidity was minimal, and all flaps survived. At 30-d postoperatively, the restoration of the lymphatic flow with the recipient limb lymphatics was observed, and histology revealed viable lymph nodes. CONCLUSIONS: The constant anatomy, the possibility to include a skin paddle and the minimal donor-site morbidity, make this flap a safe, reliable, and versatile lymph node flap supermicrosurgical model for autologous transplant in the rat for future experimental studies. PMID- 26850179 TI - Interleukin 18--binding protein ameliorates liver ischemia--reperfusion injury. AB - BACKGROUND: The aim of this study was to investigate the possible protective effect of interleukin 18-binding protein (IL-18BP) on ischemia-reperfusion (I/R) induced liver injury in experimental rat models. Liver is one of the most affected organs from I/R process. IL-18 is an important proinflammatory cytokine, which may induce some events such as production of reactive oxygen substances and release of various cytokines. IL-18BP acts as an inhibitor of IL-18. The relationship between IL-18 and IL-18BP has an important place in inflammatory process. MATERIALS AND METHODS: Rats were equally divided into three groups as follows: sham: Hepatic pedicle dissection was done, but hepatic pedicle clamping was not used. I/R: Sixty minutes of ischemia and 2 h of reperfusion were applied. IR + IL-18BP: Recombinant human IL-18BP (100 MUg/kg) was administered 30 min before the surgery. Hepatic pedicle was clamped during 60 min of ischemia and 2 h of reperfusion was achieved. RESULTS: Liver enzyme levels were significantly lower in the IR + IL-18BP group, when compared with the I/R group. Serum and tissue levels of tumor necrosis factor-alpha, IL-6, and IL-18 were considerably lower in the IR + IL-18BP group, when compared with the I/R group, but hepatic interferon-gamma and IL1beta levels were not significant. Serum oxidative stress index level was significantly higher in the I/R group, when compared with the IR + IL-18BP group. In immunostaining, it was observed that pathologic changes were lower in IR + IL-18BP group than the I/R group. CONCLUSIONS: IL-18BP exhibited anti-inflammatory, antioxidant, and protective effects in I/R-mediated hepatic injury via regulating some liver enzyme activities and cytokine levels. Additionally, these effects have been verified by histomorphologic examination and oxidative stress markers. PMID- 26850180 TI - A cadaveric procedural anatomy course enhances operative competence. AB - BACKGROUND: Inadequate anatomy training has been cited as a major contributor to declines in surgical resident operative competence and confidence. We report the impact of a procedurally oriented general surgery cadaveric dissection course on trainee-operative confidence and competence. MATERIALS AND METHODS: After obtaining institutional review board approval, postgraduate year 2 and 3 general surgery residents were prospectively enrolled into two cohorts: (1) an intervention group (n = 7) participating in an 8-wk procedurally oriented cadaver course and (2) controls (n = 7) given access to course materials without participation in cadaver dissection. At both the beginning and end of the study, we used two evaluation instruments: (1) an oral examination using standardized templates and (2) a questionnaire assessing operative confidence. RESULTS: There were no intergroup differences in baseline characteristics, including number of operative procedures performed to date. Residents who took the anatomy course had significantly higher improvements in examination scores on common bile duct exploration (mean +/- standard error, 33 +/- 8% versus 10 +/- 7%, P = 0.04), femoral endarterectomy (43 +/- 5% versus 11 +/- 7%, P = 0.003), fasciotomies (55 +/- 10% versus 22 +/- 9%, P = 0.04), inguinal hernia repair (20 +/- 9% versus -14 +/- 5%, P = 0.005), superior mesenteric artery embolectomy (38 +/- 10% versus 2 +/- 11%, P = 0.04), and in overall examination scores (31 +/- 4% versus 8% +/- 3%, P = 0.0006). In addition, they reported higher operative confidence on common bile duct exploration (P = 0.008) and superior mesenteric artery embolectomy (P = 0.02), and a trend toward higher overall operative confidence (P = 0.06). CONCLUSIONS: In this study, we demonstrate that a procedurally oriented cadaver course covering a wide range of essential general surgery procedures resulted in significant improvements in self-reported operative confidence and competence as assessed by oral examination. PMID- 26850181 TI - An in vivo analysis of Miromesh--a novel porcine liver prosthetic created by perfusion decellularization. AB - BACKGROUND: Bioprosthetics derived from human or porcine dermis and intestinal submucosa have dense, homogenous, aporous collagen structures that potentially limit cellular penetration, undermining the theoretical benefit of a "natural" collagen scaffold. We hypothesized that Miromesh-a novel prosthetic derived from porcine liver by perfusion decellularization-provides a more optimal matrix for tissue ingrowth. METHODS: Thirty rats underwent survival surgery that constituted the creation of a 4 * 1 cm abdominal defect and simultaneous bridged repair. Twenty rats were bridged with Miromesh, and 10 rats were bridged with non-cross linked porcine dermis (Strattice). Ten Miromesh and all 10 Strattice were rinsed in vancomycin solution and inoculated with 10(4) colony-forming units of green fluorescent protein-labeled Staphylococcus aureus (GFP-SA) after implantation. Ten Miromesh controls were neither soaked nor inoculated. No animals received systemic antibiotics. All animals were euthanized at 90 d and underwent an examination of their gross appearance before being sectioned for quantitative bacterial culture and histologic grading. A pathologist scored specimens (0-4) for cellular infiltration, acute inflammation, chronic inflammation, granulation tissue, foreign body reaction, and fibrous capsule formation. RESULTS: All but one rat repaired with Strattice survived until the 90-d euthanization. All quantitative bacterial cultures for inoculated specimens were negative for GFP SA. Of nine Strattice explants, none received a cellular infiltration score >0, consistent with a poor tissue-mesh interface observed grossly. Of 10 Miromesh explants also inoculated with GFP-SA, seven of 10 demonstrated cellular infiltration with an average score of +2.7 +/- 0.8, whereas sterile Miromesh implants received an average score of 0.8 +/- 1.0. Two inoculated Miromesh implants demonstrated acute inflammation and infection on histology. CONCLUSIONS: A prosthetic generated from porcine liver by perfusion decellularization provides a matrix for superior cellular infiltration compared with non-cross-linked porcine dermis. PMID- 26850182 TI - Chromogranin A predicts survival for resected pancreatic neuroendocrine tumors. AB - BACKGROUND: Currently, no serological prognostic marker exists for pancreatic neuroendocrine tumors (pNETs). Previous studies have suggested potential for chromogranin A (CgA); however, the prognostic capability of CgA remains controversial. Our purpose was to explore preoperative CgA levels in predicting outcomes in patients with resected pNETs. MATERIALS AND METHODS: Patients with preoperative CgA levels who underwent resection of a pancreatic neuroendocrine tumor between July 2002 and May 2013 were identified from a prospective database. An elevated preoperative CgA was defined as a CgA laboratory value above the normal limit of the assay. All patients had pathologically confirmed primary pancreatic tumors. Outcomes were compared between elevated and normal CgA groups. RESULTS: A total of 38 patients were identified that met inclusion criteria. Of these, 45% were male, and the median age was 57 y (range, 17-81 y). All underwent resection with curative intent. Elevated preoperative CgA was present in 16 patients (42%). There were no differences in node positivity or margin status between the normal CgA and elevated CgA groups on univariate analysis. However, tumor size and grade were significantly different between the two groups. Both disease-free survival (DFS; P = 0.006) and overall survival (P = 0.017) were negatively impacted by an elevated preoperative CgA (median follow-up; 40 mo). CONCLUSIONS: In patients with resected pNETs, an elevated preoperative CgA level was negatively associated with DFS and OS and was the only independent predictor of DFS. These results indicate that preoperative CgA may be a clinically useful prognostic marker for patients undergoing pancreatic neuroendocrine tumor resection. PMID- 26850183 TI - Argon and xenon ventilation during prolonged ex vivo lung perfusion. AB - BACKGROUND: Evidence supports the use of ex vivo lung perfusion (EVLP) as a platform for active reconditioning before transplantation to increase the potential donor pool and to reduce the incidence of primary graft dysfunction. A promising reconditioning strategy is the administration of inhaled noble gases based on their organoprotective effects. Our aim was to validate a porcine warm ischemic lung injury model and investigate postconditioning with argon (Ar) or xenon (Xe) during prolonged EVLP. METHODS: Domestic pigs were divided in four groups (n = 5 per group). In the negative control group, lungs were flushed immediately. In the positive control (PC) and treatment (Ar, Xe) groups, lungs were flushed after a warm ischemic interval of 2-h in situ. All grafts were evaluated and treated during normothermic EVLP for 6 h. In the control groups, lungs were ventilated with 70% N2/30% O2 and in the treatment groups with 70% Ar/30% O2 or 70% Xe/30% O2, respectively. Outcome parameters were physiological variables (pulmonary vascular resistance, peak airway pressures, and PaO2/FiO2), histology, wet-to-dry weight ratio, bronchoalveolar lavage, and computed tomography scan. RESULTS: A significant difference between negative control and PC for pulmonary vascular resistance, peak airway pressures, PaO2/FiO2, wet-to dry weight ratio, histology, and computed tomography-imaging was observed. No significant differences between the injury group (PC) and the treatment groups (Ar, Xe) were found. CONCLUSIONS: We validated a reproducible prolonged 6-h EVLP model with 2 h of warm ischemia and described the physiological changes over time. In this model, ventilation during EVLP with Ar or Xe administered postinjury did not improve graft function. PMID- 26850184 TI - Significance of the resection margin in bronchopulmonary carcinoids. AB - BACKGROUND: Complete surgical resection is the treatment of choice in bronchopulmonary carcinoids. Previously published data showed no inferiority of sublobar versus lobar resection. Data on the length of resection margins are lacking; thus, we aimed to analyze resection margins in pulmonary carcinoids and correlated them with survival and recurrence. METHODS: We retrospectively analyzed 85 patients who underwent surgery for atypical (AC) or typical (TC) pulmonary carcinoids. Patient charts were reviewed, and clinicopathologic and survival data were collected. Pathology reports were reviewed for length of resection margins. RESULTS: The median follow-up period was 42.3 mo (range, 0.3 172.2). There was no statistically significant difference in disease-free survival (DFS) when comparing resection margins <=2 mm to >2 mm (P = 0.93, hazard ratio = 1.7). When looking at AC alone, a worse DFS can be seen if the resection margin was smaller than 2 mm (P = 0.06, hazard ratio = 15.8). In AC, likelihood of recurrence was higher when the resection margin was <=1 cm (odds ratio = 5.1, P = 0.28). In TC, this tendency was not present (odds ratio = 1.2, P = 1). CONCLUSIONS: There is a trend toward a worse prognosis and higher likelihood of recurrence in smaller resection margins in AC in contrast to TC. Owing to low sample size, no definitive statements can be made based on this study; however, respective data on these rare tumors cannot be drawn from tumor databases. The resection margin is one of the critical issues for the treating surgeon, and any information on this topic is of highest importance to the field. PMID- 26850185 TI - Polymyxin B hemoperfusion prevents acute kidney injury in sepsis model. AB - BACKGROUND: Direct hemoperfusion with a polymyxin B-immobilized column (PMX-DHP) adsorbs endotoxin and has been used for the treatment of septic shock. Yet, the mechanisms by which PMX-DHP acts on acute kidney injury are only partially understood. MATERIALS AND METHODS: Rats were anesthetized, tracheostomized, and placed on mechanical ventilation. The animals were randomized to three groups: a cecal ligation and puncture (CLP) + dummy-DHP group (n = 10), a CLP + PMX-DHP group (n = 10), and a sham group (n = 4). Four hours after CLP, a dummy-DHP or PMX-DHP was performed for 1 h. The heart rate, mean arterial pressure, arterial blood gases, and plasma concentrations of creatinine, lactate, potassium, interleukin (IL)-6, and IL-10 were measured at 0 h and 8 h. Eight hours after CLP, the kidney was harvested, and histopathologic examination was performed. The expressions of cleaved poly (ADP-ribose) polymerase (PARP) and nuclear factor (NF)-kappaB p65 were examined by immunohistochemistry. A terminal deoxynucleotide transferase dUTP nick-end labeling assay was performed to detect apoptotic nuclei in kidney sections. RESULTS: PMX-DHP maintained hemodynamics and the acid-base balance and significantly (P < 0.05) decreased the plasma concentrations of lactate, creatinine, potassium, IL-6, and IL-10 compared with dummy-DHP. PMX-DHP significantly (P < 0.001) attenuated the expressions of cleaved PARP and NF kappaB p65 in renal tubular cells and renal tubular cell apoptosis compared with dummy-DHP. CONCLUSIONS: These findings suggest that PMX-DHP may protect against acute kidney injury not only by inhibiting the NF-kappaB signaling pathway but also by preventing renal tubular cell apoptosis. PMID- 26850186 TI - Sildenafil obviates ischemia-reperfusion injury-induced acute kidney injury through peroxisome proliferator-activated receptor gamma agonism in rats. AB - BACKGROUND: Sildenafil is a phosphodiesterase inhibitor used clinically for treating erectile dysfunction. Few studies suggest sildenafil to be a renoprotective agent. The present study investigated the involvement of peroxisome proliferator-activated receptor gamma (PPAR-gamma) in sildenafil mediated protection against ischemia-reperfusion-induced acute kidney injury (AKI) in rats. MATERIALS AND METHODS: The rats were subjected to ischemia reperfusion injury (IRI) with 40 min of bilateral renal ischemia followed by reperfusion for 24 h. The renal damage was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, electrolytes, and microproteinuria in rats. The thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels were measured to assess oxidative stress in renal tissues. The hematoxylin-eosin staining was carried out to demonstrate histopathologic changes in renal tissues. Sildenafil (0.5 and 1.0 mg/kg, intraperitoneal) was administered 1 h before subjecting the rats to renal IRI. In a separate group, bisphenol A diglycidyl ether (30 mg/kg, intraperitoneal), a PPAR-gamma receptor antagonist, was given before sildenafil administration followed by IRI. RESULTS: The ischemia-reperfusion demonstrated marked AKI with significant changes in serum and urinary parameters, enhanced oxidative stress, and histopathologic changes in renal tissues. The administration of sildenafil demonstrated significant protection against ischemia reperfusion-induced AKI. The prior treatment with bisphenol A diglycidyl ether abolished sildenafil-mediated renal protection, thereby confirming involvement of PPAR-gamma agonism in the sildenafil-mediated renoprotective effect. CONCLUSIONS: It is concluded that sildenafil protects against ischemia-reperfusion-induced AKI through PPAR-gamma agonism in rats. PMID- 26850187 TI - Interleukin 6 production during cardiac surgery correlates with increasing age. AB - BACKGROUND: Cardiac surgery produces a proinflammatory response characterized by cytokine production. Proinflammatory cytokines such as interleukin 6 (IL-6) may contribute to morbidity and mortality after cardiopulmonary bypass (CPB). Elderly patients undergoing CPB are at increased risk of morbidity and mortality. We hypothesized that patients aged >70 y produce more IL-6 during CPB. METHODS: Twenty-three patients (ages 23-80) undergoing cardiac surgery had blood sampled from the ascending aorta and coronary sinus on initial cannulation for bypass, at 30 min of aortic cross-clamp time, on release of the aortic cross-clamp, and at 20 min after reperfusion. Group 1 patients (n = 8) were aged <60 y, group 2 patients (n = 7) were aged between 60 and 70 y, and group 3 patients (n = 8) were aged >70 y. Plasma levels of tumor necrosis factor-alpha, IL-1, and IL-6 were analyzed. RESULTS: The three groups did not differ with respect to preoperative ejection fraction, New York Heart Association classification, mean aortic cross clamp time, or mean CPB time. IL-6 levels rose throughout myocardial ischemia and reperfusion in all three age groups. The increase in IL-6 during ischemia and reperfusion in the age group >70 was greater than the increase in younger patients. IL-6 was similar in the coronary sinus and the ascending aorta. CONCLUSIONS: These data suggest that patients aged >70 y undergoing cardiac operations generate more IL-6 during CPB. The increased circulating IL-6 in elderly patients may incite a proinflammatory state that could subsequently underlie the associated higher mortality and morbidity of these procedures in elderly patients. PMID- 26850188 TI - Can a nickel-titanium memory-shape device serve as a substitute for the stapler in gastrointestinal anastomosis? A systematic review and meta-analysis. AB - BACKGROUND: Recently, a nickel-titanium (NiTi) memory-shape device has been successfully used in gastrointestinal anastomosis. The aim of this study was to investigate the feasibility and safety of the device. METHODS: Four databases, reference lists, and the World Health Organization International Clinical Trials Registry Platform were systematically searched for randomized controlled trials assessing the clinical efficacy of a NiTi memory-shape device compared with that of a stapler in gastrointestinal or colorectal anastomosis. RESULTS: Seven randomized controlled trials regarding the use of compression anastomosis clips (CACs) were enrolled for meta-analysis. The use of CACs was associated with a significant reduction in hospital duration (mean = -0.88 d; 95% confidence interval [CI], -1.38 to -0.38), the time to flatus (mean = -0.36 d; 95% CI, -0.08 to -0.04), and the start of oral intake (mean = -0.45 d; 95% CI, -0.83 to -0.06), as well as a nonsignificant change in postoperative complications and mortality. These clinical outcomes did not significantly change with the use of compression anastomosis rings. CONCLUSIONS: Colonic anastomosis with a CAC is likely to reduce hospital duration, time to flatus, and the start of oral intake without influencing mortality or postoperative complications and may be a safe and preferable choice in colonic anastomosis. Further well-designed trials should be performed to determine the safety and efficacy of the newly developed compression anastomosis ring in both ileocolic and colorectal anastomosis. PMID- 26850189 TI - Experimental replacement of esophagus with a short segment of trachea. AB - BACKGROUND: Segmental resection of esophagus with primary anastomosis is prohibited because of the risk of dehiscence. We previously have shown that replacement of a segment of cervical esophagus with a tracheal segment of the same length could successfully be performed in a canine model. In this study, we sought to assess the feasibility of replacement of the esophageal defect with a shorter segment of trachea. METHODS: In five mongrel dogs weighting 20-30 kg, under general anesthesia and after a cervical incision, 8 cm of the cervical esophagus was resected and replaced by a 4-cm segment of the adjacent trachea. The animals were evaluated clinically for signs and symptoms of stenosis and dehiscence and then euthanized after 2 mo of follow-up. RESULTS: All dogs recovered from surgery and started regular diet on the seventh postoperative day. No clinical or endoscopic sign of stenosis or voice change was seen. Squamous metaplasia and atrophy of mucosal glands and cartilage were detected in the histopathologic examination of the replaced segments. CONCLUSIONS: Replacement of a cervical esophageal defect with a shorter segment of trachea can be performed successfully in dogs. This procedure can be potentially used for the treatment of cervical esophageal lesions in humans. PMID- 26850190 TI - Mobile spaced education for surgery rotation improves National Board of Medical Examiners scores. AB - BACKGROUND: Use of mobile devices for medical education is increasing. The aim of this study was to describe the implementation of a spaced education-based app study program in a third year medical school surgery rotation and examine its effects on National Board of Medical Examiners (NBME) examination performance. MATERIALS AND METHODS: Case-based questions were created and distributed to students on a voluntary basis via a mobile app. Questions were repeated in a spaced based manner until mastered. Students completed surveys regarding study habits and app use. NBME examination scores and prior academic measures were obtained. Users of the app were compared to non-users of the app and the previous years' class. RESULTS: One hundred fifty-two students were offered the app; 121 (80%) used it. App users had a final NBME score of 77.5% compared with 68.8% (P < 0.01) in non-users, although their prior academic achievement was better. Categorizing them by their academic achievement and intensity of app use demonstrated significantly higher scores in regular users of the app as compared with casual and non-users in mid (78 versus 75 versus 71.2%, P < 0.01) and low achieving students (71.4 versus 70 versus 64.6, P < 0.01), but not high-achieving students (85.3 versus 81.1 versus 79.7, P = 0.09). Stepwise linear regression modeling revealed intensity of app use accounted for 6% of the variance in NBME scores. CONCLUSIONS: Use of the app-based program was an effective tool associated with higher scores on standardized tests in lower level achieving students. PMID- 26850191 TI - Efficacy of triclosan-coated sutures for reducing risk of surgical site infection in adults: a meta-analysis of randomized clinical trials. AB - BACKGROUND: Surgical site infection (SSI) is the third most frequent type of nosocomial infections. Triclosan-coated sutures are often used to reduce the risk of SSI, but studies examining this have given conflicting results. Therefore, this meta-analysis was performed to assess the efficacy of triclosan-coated sutures for reducing risk of SSI in adults. METHODS: PubMed, EMBASE, Google Scholar, and ClinicalTrials.gov were searched to identify randomized clinical trials evaluating triclosan-coated sutures for preventing SSI on patients 18 y or older. RESULTS: Thirteen randomized clinical trials involving 5256 participants were included. Triclosan-coated sutures were associated with lower risk of SSI than uncoated sutures across all surgeries (risk ratio [RR] 0.76, 95% confidence interval [CI] 0.65-0.88, P < 0.001). Similar proportions of patients experienced wound dehiscence with either type of suture (RR 0.97, 95% CI 0.49-1.89, P = 0.92). Subgroup analysis showed lower risk of SSI with triclosan-coated sutures in abdominal surgeries (RR 0.70, 95% CI 0.50-0.99, P = 0.04) and group with prophylactic antibiotic (RR 0.79, 95% CI 0.63-0.99, P = 0.04). However, such risk reduction was not observed in cardiac surgeries, breast surgeries, or group without prophylactic antibiotic. CONCLUSIONS: Triclosan-coated sutures can decrease the incidence of SSI in abdominal surgeries and might not interfere with wound healing process. Nevertheless, further studies are needed to examine whether triclosan-coated sutures are effective at preventing SSI in non-abdominal surgeries and to further study the interaction of antibiotic prophylaxis with triclosan-coated sutures. PMID- 26850192 TI - Acute appendicitis: variation in outcomes by insurance status. AB - BACKGROUND: Acute appendicitis (AA) is often studied as a surrogate for acute care surgery. Previous studies have shown differences in outcomes based on insurance status, but associated costs to health care systems are in need of further study. The purpose of the present study was to investigate how treatment, outcomes, and health care resource utilization differ between the uninsured and commercially insured in the setting of AA. METHODS: Patients with AA were identified by International Classification of Diseases, ninth edition, codes using the Agency for Health Care Administration Florida Hospital inpatient discharge data sets for 2002-2011. The outcomes studied were admission with complicated versus uncomplicated appendicitis, receiving laparoscopic versus open appendectomy and experiencing a perioperative complication, length of stay, and overall hospital cost. Data were analyzed using logistic, negative binomial, and least squares multivariate regression. A P value <0.05 was considered significant. All equations controlled for patient demographics, comorbidities, and year and hospital-fixed effects. RESULTS: The uninsured were more likely to present with complicated appendicitis (odds ratio = 1.31, P < 0.01), less likely to receive laparoscopic appendectomy (odds ratio = 0.70, P < 0.01), had longer length of stay, greater costs but had similar rates of perioperative complications in comparison to the commercially insured. CONCLUSIONS: Insurance status is known to affect health care utilization. The uninsured may delay seeking medical assistance, causing greater incidence of complicated disease and increased costs of treatment. Increasing the number of insured via the Affordable Care Act may improve patient outcomes and decrease costs related to AA. These findings may also apply to other acute care surgery conditions. PMID- 26850193 TI - A national trauma capacity assessment of Haiti. AB - BACKGROUND: Trauma systems in high-income countries have been shown to reduce trauma-related morbidity and mortality; however, these systems are infrequently implemented in low- and middle-income countries. Haiti currently lacks a well resourced and structured trauma system and in turn loses an estimated 800,000 y of healthy life to injuries annually. In the present study, we perform a nationwide trauma capacity assessment, and using the World Health Organization's Guidelines for Essential Trauma Care as a framework, we attempt to identify achievable steps that can be taken toward improving trauma care in Haiti. MATERIALS AND METHODS: This cross-sectional study was performed at 12 facilities nationally using a survey tool assessing the areas of infrastructure, supplies and equipment, personnel and training, and procedural capabilities. Additionally, the total number of trauma cases presenting to each facility was tabulated from emergency room logbooks. RESULTS: A total of six secondary and six tertiary facilities were surveyed. Secondary facilities received an average of 35 trauma cases per week, whereas tertiary facilities received an average of 65 cases per week. Survey results demonstrated a shortage of airway, breathing, and circulation equipment and supplies in both facility levels, particularly in emergency rooms. All facilities lacked access to essential surgical personnel and trauma training. CONCLUSIONS: This study makes recommendations for improvements in trauma care in Haiti in the areas of infrastructure and administration, physical resources, and training and human resources. These recommendations represent feasible steps that can be taken toward the construction of a national trauma system in Haiti. PMID- 26850194 TI - Nonoperative management of splenic injuries: significance of age. AB - BACKGROUND: In the nonoperative management (NOM) of blunt splenic injuries (BSI), the clinical relevance of age as a risk factor has not been well studied. METHODS: Using the 2011 National Trauma Data Bank data set, age was analyzed both as a continuous variable and a categorical variable (group 1 [13-54 y], group 2 [55-74 y], and group 3 [>=75 y]). BSI severity was stratified by abbreviated injury scale (AIS): group 1 (AIS <=2), group 2 (AIS 3), and group 3 (AIS >=4). A semiparametric proportional odds model was used to model NOM outcomes and effects due to age and BSI severity. RESULTS: Of 15,113 subjects, 15.3% failed NOM. The odds of failure increased by a factor of 1.014 for each year of age, or factor of 1.5 for groups 2 and 3 each. BSI severity groups 2 and 3 had increases in the odds of failure by factors of 3.9 and 13, respectively, compared with those of group 1. Most failures occurred by 48 h irrespective of age. The effect of age was most pronounced in age groups 2 and 3 with the most severe BSI, where a NOM failure rate of >50% was seen. Both age and failure of NOM were independent predictors of mortality. CONCLUSIONS: Age is associated with failure of NOM but its effect seems more clinically relevant only in high-grade BSI. Factors that could influence NOM success in elderly patients with high-grade injuries deserve further study. PMID- 26850195 TI - Identification of proteins regulated by curcumin in cerebral ischemia. AB - BACKGROUND: Curcumin is known to have a neuroprotective effect against cerebral ischemia. The objective of this study was to identify various proteins that are differentially expressed by curcumin treatment in focal cerebral ischemia using a proteomic approach. METHODS: Adult male rats were treated with vehicle or curcumin 1 h after middle cerebral artery occlusion. Brain tissues were collected 24 h after the onset of middle cerebral artery occlusion, and cerebral cortices proteins were identified by two-dimensional gel electrophoresis and mass spectrometry. RESULTS: We detected several proteins with altered expression levels between vehicle- and curcumin-treated animals. Among these proteins, ubiquitin carboxy-terminal hydrolase L1, isocitrate dehydrogenase, adenosylhomocysteinase, and eukaryotic initiation factor 4A were decreased in the vehicle-treated animal, and curcumin treatment attenuated the injury-induced decreases of these proteins. Conversely, pyridoxal phosphate phosphatase was increased in the vehicle-treated animal, and curcumin treatment prevented decreases in this protein. The identified altered proteins are associated with cellular metabolism and differentiation. CONCLUSIONS: The results of this study suggest that curcumin exerts a neuroprotective effect by regulating the expression of various proteins in focal cerebral ischemia. PMID- 26850196 TI - A comparison of suction and full-thickness rectal biopsy in children. AB - BACKGROUND: Rectal biopsy evaluation by an experienced pathologist is the gold standard in diagnosis of Hirschsprung's disease (HD). Although both suction rectal biopsy (SRB) and full-thickness (FTRB) rectal biopsy are performed, the ability for SRB to obtain adequate tissue in older children has been questioned. We hypothesized that SRB and FTRB yield tissue specimens of different size but are equally adequate for diagnosis. METHODS: Records of children who underwent rectal biopsy to evaluate for HD between January 2007 and July 2014 were reviewed. Volume, percent submucosa, and specimen adequacy were compared between biopsy techniques, and the effect of age on biopsy adequacy was assessed. Data were analyzed by mixed-effects models with covariate adjustment for age at biopsy and Fisher's exact test. RESULTS: Forty-seven children underwent a total of 58 biopsies, 45 SRB and 13 FTRB. Thirty-seven were performed before 12 mo of age, and 21 after 12 mo of age. Volume of SRB specimens was significantly smaller than FTRB across ages (14.8 +/- 7.8 mm(3)versus 121.3 +/- 13.8 mm(3), P = 0.0001). Percent submucosa did not differ significantly between SRB and FTRB specimens across ages (63.8 +/- 2.7% versus 66.5 +/- 4.3%, P = 0.575). The number of inadequate biopsies was low and not significantly different across ages (P = 0.345), or when comparing by biopsy method (P = 0.689). All biopsies were clinically diagnostic. There were no complications. CONCLUSIONS: Tissue specimens obtained by SRB are smaller than those obtained by FTRB, especially in older children. SRB and FTRB appear equivalent in their ability to provide adequate submucosa. Differences in cost and patient satisfaction between rectal biopsy techniques must be studied to further define the best overall technique. PMID- 26850197 TI - Gender and frailty predict poor outcomes in infrainguinal vascular surgery. AB - BACKGROUND: Women have poorer outcomes after vascular surgery as compared to men as shown by studies recently. Frailty is also an independent risk factor for postoperative morbidity and mortality. This study examines the interplay of gender and frailty on outcomes after infrainguinal vascular procedures. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to identify all patients who underwent infrainguinal vascular procedures from 2005-2012. Frailty was measured using a modified frailty index (mFI; derived from the Canadian Study of Health and Aging). Univariate and multivariate analysis were performed to investigate the association of preoperative frailty and gender, on postoperative outcomes. RESULTS: Of 24,645 patients (92% open, 8% endovascular), there were 533 deaths (2.2%) and 6198 (25.1%) major complications within 30 d postoperatively. Women were more frail (mean mFI = 0.269) than men (mean mFI = 0.259; P < 0.001). Women and frail patients (mFI>0.25) were more likely to have a major morbidity (P < 0.001) or mortality (P < 0.001) with the highest risk in frail women. On multivariate logistic regression analysis, female gender and increasing mFI were independently significantly associated with mortality (P < 0.05) as well as major complications. The interaction of gender and frailty in multivariate analysis showed the highest adjusted 30-d mortality and morbidity in frail females at 2.8% and 30.1%, respectively and that was significantly higher (P < 0.001) than nonfrail males, nonfrail females and frail males. CONCLUSIONS: Female gender and frailty are both associated with increased risk of complications and death following infrainguinal vascular procedures with the highest risk in frail females. Further studies are needed to explore the mechanisms of interaction of gender and frailty and its effect on long-term outcomes for peripheral vascular disease. PMID- 26850198 TI - Immune status does not predict high-risk HPV in anal condyloma. AB - BACKGROUND: More than 90% of anal condyloma is attributed to nonhigh risk strains of human papillomavirus (HPV), thus patients with anal condyloma do not necessarily undergo HPV serotyping unless they are immunocompromised (IC). We hypothesized that IC patients with anal condyloma have a higher risk of high-risk HPV and dysplasia than nonimmunocompromised (NIC) patients. METHODS: We performed a retrospective chart review of patients who underwent surgical treatment by a single surgeon for anal condyloma from 1/2000 to 1/2012. HPV serotyping was performed on all patient samples. We compared incidence of high-risk HPV and dysplasia in condyloma specimens from IC and NIC patients. RESULTS: High-risk HPV was identified in 14 specimens with serotypes 16, 18, 31, 33, 51, 52, and 67. Twenty-two cases (18.3%) had dysplasia. Invasive carcinoma was identified in one IC patient. The prevalence of dysplasia or high-risk HPV was not significantly different between IC and NIC groups. High-risk HPV was a significant independent predictor of dysplasia (odds ratio [OR] = 5.2; 95% CI = 1.24-21.62). Immune status, however, was not a significant predictor of high-risk HPV (OR = 1.11; 95% CI = 0.16-5.12) nor dysplasia (OR = 0.27; 95% CI = 0.037-1.17). CONCLUSIONS: IC patients did not have a significantly higher prevalence or risk of high-risk HPV or dysplasia in our study. HPV typing of all condylomata, regardless of immune status, should be considered as it may help predict risk of neoplastic transformation or identify NIC patients with an increased risk of developing anal intraepithelial neoplasia. PMID- 26850200 TI - Non-weight-based enoxaparin dosing subtherapeutic in trauma patients. AB - BACKGROUND: We report our experience dosing and monitoring enoxaparin with anti factor Xa activity (anti-FXaA) levels for venous thromboembolism prophylaxis in trauma patients (TP). MATERIALS AND METHODS: TP receiving standard, non-weight based dosed enoxaparin administered every 12 h for venous thromboembolism prophylaxis with peak anti-FXaA levels measured were prospectively monitored and evaluated and those whose first anti-FXaA levels >= or <0.2 IU/mL were compared. Anti-FXaA levels and enoxaparin dose (mg/kg actual body weight) were evaluated for correlation. RESULTS: Of the fifty-one TP included, initial anti-FXaA levels were <0.2 IU/mL in 37 (72.5%) whose dose was lower than those within target range (0.38 [0.32-0.42] mg/kg versus 0.45 [0.39-0.48] mg/kg, P = 0.003). Thirty-seven TP achieved anti-FXaA level >=0.2 IU/mL (23 requiring dose increases) at a dose of 0.49 [0.44-0.54] mg/kg. Correlation between dose and anti-FXaA levels for the initial 51 anti-FXaA levels (r = 0.360, P = 0.009) and for all 103 anti-XaA levels (r = 0.556, P < 0.001) was noted. CONCLUSIONS: Non-weight-based enoxaparin dosing did not achieve target anti-FXaA levels in most TP. Higher anti-FXaA levels correlated with larger weight-based enoxaparin doses. Weight-based enoxaparin dosing (i.e., 0.5 mg/kg subcutaneously every 12 h) would better achieve target anti-FXaA levels. PMID- 26850199 TI - Novel method to assess arterial insufficiency in rodent hind limb. AB - BACKGROUND: Lack of techniques to assess maximal blood flow capacity thwarts the use of rodent models of arterial insufficiency to evaluate therapies for intermittent claudication. We evaluated femoral vein outflow (VO) in combination with stimulated muscle contraction as a potential method to assess functional hind limb arterial reserve and therapeutic efficacy in a rodent model of subcritical limb ischemia. MATERIALS AND METHODS: VO was measured with perivascular flow probes at rest and during stimulated calf muscle contraction in young, healthy rats (Wistar Kyoto, WKY; lean Zucker rats, LZR) and rats with cardiovascular risk factors (spontaneously hypertensive [SHR]; obese Zucker rats [OZR]) with acute and/or chronic femoral arterial occlusion. Therapeutic efficacy was assessed by administration of Ramipril or Losartan to SHR after femoral artery excision. RESULTS: VO measurement in WKY demonstrated the utility of this method to assess hind limb perfusion at rest and during calf muscle contraction. Although application to diseased models (OZR and SHR) demonstrated normal resting perfusion compared with contralateral limbs, a significant reduction in reserve capacity was uncovered with muscle stimulation. Administration of Ramipril and Losartan demonstrated significant improvement in functional arterial reserve. CONCLUSIONS: The results demonstrate that this novel method to assess distal limb perfusion in small rodents with subcritical limb ischemia is sufficient to unmask perfusion deficits not apparent at rest, detect impaired compensation in diseased animal models with risk factors, and assess therapeutic efficacy. The approach provides a significant advance in methods to investigate potential mechanisms and novel therapies for subcritical limb ischemia in preclinical rodent models. PMID- 26850201 TI - Prognostic value of ABO blood group in patients with gastric cancer. AB - BACKGROUND: Previous studies have shown a link between the ABO blood groups and prognoses for several types of malignancies. However, little is known about the relationship between the ABO blood groups and prognosis in patients with gastric cancer (GC). The aim of this study was to investigate the prognostic performance of ABO blood groups in patients with GC. METHODS: A total of 1412 GC patients who had undergone curative intent surgery between January 2005 and January 2010 participated in the present study. A prognostic nomogram was constructed to improve the predictive capacity for patients with gastrectomy using R software, and its predictive accuracy was determined by the concordance index (c-index). RESULTS: The median follow-up period of the 1412 GC patients was 44 mo with 809 alive. Non-AB blood groups were associated with significantly decreased overall survival in GC patients (hazard ratio = 2.59; 95% confidence interval = 1.74 3.86, P < 0.001), but patients in the group AB had a better prognosis than those in the non-AB blood groups. Meanwhile, group A had the worst prognosis among all the blood groups (hazard ratio = 3.14; 95% confidence interval = 2.09-4.72; P < 0.001). In addition, our constructed nomogram, superior to that of the traditional AJCC stage system (c-index: 0.69), could more accurately predict overall survival (c-index: 0.78) in GC patients who had undergone gastrectomy. CONCLUSIONS: The blood group AB is a favorable prognostic factor for GC patients, but the blood group A is an adverse prognostic factor for patients with gastrectomy. Further prospective studies are warranted to confirm this relationship. PMID- 26850202 TI - Conditional survival in advanced colorectal cancer and surgery. AB - BACKGROUND: Recent data show patients with advanced colorectal cancer (CRC) are surviving longer. What is unknown is how specific treatment modalities affect long-term survival. Conditional survival, or survival prognosis based on time already survived, is becoming an acceptable means of estimating prognosis for long-term survivors. We evaluated the impact of cancer-directed surgery on long term survival in patients with advanced CRC. METHODS: We used Surveillance, Epidemiology, and End Results data to identify 64,956 patients with advanced (Stage IV) CRC diagnosed from 2000-2009. Conditional survival estimates by stage, age, and cancer-directed surgery were obtained based on Cox proportional hazards regression model of disease-specific survival. RESULTS: A total of 64,956 (20.1%) patients had advanced disease at the time of diagnosis. The proportion of those patients who underwent cancer-directed surgery was 65.1% (n = 42,176). Cancer directed surgery for patients with advanced stage disease was associated with a significant improvement in traditional survival estimates compared to patients who did not undergo surgery (hazard ratio = 2.22 [95% confidence interval, 2.17 2.27]). Conditional survival estimates show improvement in conditional 5-y disease-specific survival across all age groups, demonstrating sustained survival benefits for selected patients with advanced CRC. CONCLUSIONS: Five-year disease specific conditional survival improves dramatically over time for selected patients with advanced CRC who undergo cancer-directed surgery. This information is important in determining long-term prognosis and will help inform treatment planning for advanced CRC. PMID- 26850203 TI - More compression improves sealing effect on larger pulmonary arteries. AB - BACKGROUND: Small arteries and veins up to 7 mm can be sealed safe and divided with a bipolar sealing instrument. The results for the safe sealing of larger vessels were unsatisfactory in the past. Using an ex vivo pulmonary artery model, we aimed to investigate, if a higher compression force and duration will improve the bursting pressures in case of vessels >7 mm. MATERIAL AND METHODS: Heart-lung preparations (from 90 kg pigs) were removed en bloc at a slaughterhouse. The whole pulmonary artery was exposed from the pulmonary valve up to the periphery of the left lung. In the laboratory, a digital pressure sensor was implanted in the central end of the blood vessel to measure the bursting pressure (in mbar). The vessels examined were divided into three groups by diameter: 1-6 mm, 7-12 mm and >12 mm. After bipolar sealing, bursting pressures were determined by pneumatic testing. Seals were made using three equal MARSEAL instruments (Gebruder Martin GmbH & CoKG, Tuttlingen, Germany) with a SealSafe G3 electric current and different jaw compression forces of each 35 N, 45 N, and 55 N. Bursting pressures were also measured for different compression durations (0 s, 5 s, 10 s, and 20 s) with 35 N compression. Mean bursting pressures were calculated for each group (n = 15). Groups were compared using a nonparametric test (Mann Whitney U test). The significance level was P < 0.05. RESULTS: Mean bursting pressures in the 1-6 mm blood vessels were 290.5 +/- 77.1 mbar (35 N), 323.0 +/- 76.0 mbar (45 N) and 301.6 +/- 69.9 mbar (55 N). The groups did not differ significantly. Mean bursting pressures in the 7-12 mm vessels were 108.1 +/- 19.1 mbar (35 N), 154.3 +/- 28.5 mbar (45 N), and 212.4 +/- 45.3 mbar (55 N). In blood vessels >12 mm in diameter, we found mean bursting pressures of 77.7 +/- 11.7 mbar (35 N), 117.6 +/- 27.1 mbar (45 N), and 166.3 +/- 56.6 mbar (55 N). The results for the groups with 55 N compression were significantly higher than for the other groups. A compression duration of 5 s led to significantly higher mean bursting pressures than a duration of 0 s but a duration of >5 s did not bring a further significant increase in mean bursting pressure. Histologic staining of the seal zone and microscopic examination did not reveal any differences relating to compression force. CONCLUSIONS: With a higher compression force, we reached satisfactory bursting pressures in case of pulmonary arteries >7 mm. An additional 5 s of compression before starting coagulation brings a further significant increase in bursting pressure. However, there is no advantage in a longer compression. PMID- 26850204 TI - Dividing inferior pulmonary ligament may change the bronchial angle. AB - BACKGROUND: Whether dissecting the inferior pulmonary ligaments (IPLs) during superior video-assisted thoracoscopic (VATS) lobectomy for early stage lung cancer remains controversial. This study aimed to evaluate the influence of dissecting the IPLs during VATS superior lobectomy on bronchial distortion and recovery of pulmonary function. MATERIALS AND METHODS: This was a retrospective study of 72 patients with non-small cell lung cancer who underwent VATS superior lobectomy from March 2012-August 2013 at the First People's Hospital of Yunnan Province. Patients were grouped according to IPLs preservation (group P) or dissection (group D). The preoperative and postoperative pulmonary function and the postoperative complications were analyzed. The changes in bronchi angles and pulmonary capacity were measured using computed tomography. RESULTS: There were no significant differences in the complication rate and volume of chest drainage between the two groups. The changes in bronchus angle in group P were significantly smaller than those in group D after left lung operation (P = 0.046 at 3 mo; P = 0.038 at 6 mo); in the right lung, the changes were not significant between the two groups (P = 0.057 at 3 mo; P = 0.541 at 6 mo). The forced expiratory volume of 2% and forced expiratory volume in 1 s (FEV1%) were significantly better in group P than those in group D at 3 and 6 mo (P < 0.05). The pulmonary capacity in group P was significantly larger than that in group D at 6 mo (P = 0.002). CONCLUSIONS: Preservation of IPLs during VATS lobectomy might have an impact on the bronchus angle, lung function, and lung volume. PMID- 26850205 TI - Atrial natriuretic peptide attenuation of renal ischemia-reperfusion injury after major surgery. AB - BACKGROUND: Ischemia-reperfusion (I/R) injury is one of the most important pathologic processes causing acute kidney injury. Human atrial natriuretic peptide (hANP) has various effects, including renal protection. The purpose of the present work was to study the effects of intrarenal angiotensin II (Ang II) and investigate the potential of hANP to prevent kidney injury. MATERIALS AND METHODS: Male Sprague-Dawley rats were divided into three groups as follows: (1) sham; (2) I/R (30 min of bilateral renal ischemia followed by 6 h reperfusion); and (3) I/R + hANP (I/R injury + continuous intravenous infusion of hANP at 0.025 MUg/kg/min). After 6 h of reperfusion, both renal and plasma Ang II concentrations were measured. Urinary angiotensinogen and neutrophil gelatinase associated lipocalin were measured before ischemia and 2, 4, and 6 h after reperfusion. To evaluate the renal-protective effects of hANP, serum creatinine was determined 6 and 24 h after reperfusion. In addition, mitochondrial oxygen consumption in kidney cortex was measured in the presence of Ang II and hANP. RESULTS: Renal Ang II concentrations were 24.5 +/- 3.9 and 14.2 +/- 3.4 pg/mg renal weight in the I/R and I/R + hANP groups, respectively. Urinary angiotensinogen and neutrophil gelatinase-associated lipocalin excretions were elevated after I/R injury. Treatment with hANP significantly attenuated this effect after 4 and 6 h. Oxygen consumption in renal mitochondria increased with the addition of Ang II, which was also attenuated by hANP. CONCLUSIONS: Production of intrarenal Ang II was attenuated by hANP, indicating a potential to diminish renal I/R injury. PMID- 26850206 TI - Resident training in a new robotic thoracic surgery program. AB - BACKGROUND: The volume of robot-assisted operations has drastically increased over the past decade. New programs have focused on training surgeons, whereas resident training has lagged behind. The objective of this study was to evaluate our institutional experience with resident participation in thoracic robotic surgery cases since the initiation of our program. METHODS: The first 100 robotic thoracic surgery cases at our institution were retrospectively reviewed and categorized into three sequential cohorts. Procedure type, patient and operative characteristics, level of resident participation (primary surgeon [PS] or assistant), and postoperative variables were evaluated. RESULTS: Of the first 100 cases, 38% were lung resections, 23% were esophageal operations, and 20% were sympathectomies. The distribution of cases changed over time with the proportion of pulmonary resections significantly increasing. Patient age (P < 0.05), body mass index (P = not significant [NS]), and comorbidities (P = NS) increased over time. Resident participation as PS increased from 33%-59% between the early and late cohorts (P < 0.05). A subset analysis of the 20 lobectomies (7 attending PS, 13 residents) showed similar patient characteristics (P = NS): age (67 versus 69), body mass index (29.5 versus 26.1), and American Society of Anesthesiologists category (2.8 versus 2.8). Operative and postoperative characteristics were also similar (P = NS) regardless of PS: operative time (260 versus 249 min), estimated blood loss (187 versus 203 mL), and length of stay (4.8 versus 4.7 d). CONCLUSIONS: Residents can participate as the PS in a variety of thoracic operations during the implementation of a robotics program. Operative time, estimated blood loss, and length of stay were similar regardless of level of resident participation. PMID- 26850207 TI - Ghrelin ameliorates adhesions in a postsurgical mouse model. AB - BACKGROUND: Peritoneal adhesion formation is a well-recognized consequence of abdominal and pelvic surgery, causing infertility, chronic pelvic pain, and intestinal obstruction. We hypothesized that ghrelin, a 28-amino acid peptide predominantly found in the stomach, plays an important role in preventing postoperative surgical adhesions. The purpose of this study was to develop a new surgical peritoneal adhesion model to define the role that ghrelin plays in wound healing and adhesion formation. MATERIALS AND METHODS: C57BL/6 wild-type mice (n = 40) and growth hormone secretagogue receptor-knockout (GHSR KO) mice (n = 20) underwent a midline laparotomy to establish a peritoneal adhesion model characterized by the combination of two different techniques: ischemic peritoneal buttons and cecal multiple abrasion. All mice received intraperitoneal injections with ghrelin (0.16 mg/kg) or saline twice daily for 20 d after surgery. Peritoneal ischemic buttons were harvested to determine protein expression of collagen (Masson trichrome, picrosirius red stain, and Western blot). RESULTS: The novel mouse model demonstrated consistent and easily reproducible formation of intra-abdominal adhesions. Ghrelin administration significantly reduced postoperative adhesion formation (P < 0.001) in wild-type mice. The antifibrotic effect of ghrelin in wild-type mice was confirmed by measuring collagen I protein levels via Western blot analysis. The anti-adhesion effect of ghrelin seen in wild-type mice was not detected in GHSR KO mice demonstrating that this effect is mediated by the GHSR-1a receptor. CONCLUSIONS: Ghrelin administration may improve surgical outcome by reducing peritoneal adhesion formation and fibrotic response in a mouse model. PMID- 26850208 TI - Impact of video game genre on surgical skills development: a feasibility study. AB - BACKGROUND: The playing of video games (VGs) was previously shown to improve surgical skills. This is the first randomized, controlled study to assess the impact of VG genre on the development of basic surgical skills. MATERIALS AND METHODS: Twenty first-year, surgically inexperienced medical students attended a practical course on surgical knots, suturing, and skin-flap technique. Later, they were randomized into four groups: control and/or nongaming (ContG), first person-shooter game (ShotG), racing game (RaceG), and surgery game (SurgG). All participants had 3 wk of Nintendo Wii training. Surgical and VG performances were assessed by two independent, blinded surgeons who evaluated basal performance (time 0) and performance after 1 wk (time 1) and 3 wk (time 2) of training. RESULTS: The training time of RaceG was longer than that of ShotG and SurgG (P = 0.045). Compared to SurgG and RaceG, VG scores for ShotG improved less between times 0 and 1 (P = 0.010) but more between times 1 and 2 (P = 0.004). Improvement in mean surgical performance scores versus time differed in each VG group (P = 0.011). At time 2, surgical performance scores were significantly higher in ShotG (P = 0.002) and SurgG (P = 0.022) than in ContG. The surgical performance scores of RaceG were not significantly different from the score achieved by ContG (P = 0.279). CONCLUSIONS: Different VG genres may differentially impact the development of surgical skills by medical students. More complex games seem to improve performance even if played less. Although further studies are needed, surgery-related VGs with sufficient complexity and playability could be a feasible adjuvant to improving surgical skills. PMID- 26850209 TI - Increased rates of advanced thyroid cancer in California. AB - BACKGROUND: We have noted an unusually high rate of advanced thyroid cancers presenting from across California. We examined the rates of thyroid cancer presentation throughout California for potential geographic clustering. MATERIALS AND METHODS: A total of 26,983 patients with a new diagnosis of thyroid cancer (1999-2008) were abstracted from the California Cancer Registry and the Office of Statewide Health Planning and Development registry. Percentages of advanced thyroid cancer rates were calculated within each county (defined as those with distant metastatic stage; regional and/or distant metastatic stage [RM]) as well as those with well-differentiated thyroid cancer diagnosed before age 30. National averages were taken from Surveillance, Epidemiology, and End Results (SEER) data. RESULTS: There was no obvious clustering of advanced cases within certain regions in California; however, on average, the entire state of California had significantly higher rates of distant metastatic thyroid cancer (6.73%) and RM (34.92%) than the national SEER averages (4%, 29%, respectively, P < 0.001). Of the 47 California counties, 20 had significantly higher percentages of distant metastatic thyroid cancer than the national SEER average (range, 6% 13% versus 4%, P < 0.05), and 20 had a higher percentage of RM than the national SEER average (range, 35%-48% versus 29%, P < 0.05). Two California counties had higher rates of young patients with well-differentiated thyroid cancer (range, 14.29%-17.9%) than the national SEER average (12%). CONCLUSIONS: California exhibits more advanced thyroid cancers than the national SEER population average. Further studies are warranted to better understand etiologies for these disparities, which may include environmental impacts and/or delays in diagnosis. PMID- 26850210 TI - Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. AB - Noninvasive brain stimulation has been demonstrated to modulate cortical activity in humans. In particular, theta burst stimulation (TBS) has gained notable attention due to its ability to induce lasting physiological changes after short stimulation durations. The present study aimed to provide a comprehensive meta analytic review of the efficacy of two TBS paradigms; intermittent (iTBS) and continuous (cTBS), on corticospinal excitability in healthy individuals. Literature searches yielded a total of 87 studies adhering to the inclusion criteria. iTBS yielded moderately large MEP increases lasting up to 30 min with a pooled SMD of 0.71 (p<0.00001). cTBS produced a reduction in MEP amplitudes lasting up to 60 min, with the largest effect size seen at 5 min post stimulation (SMD=-0.9, P<0.00001). The collected studies were of heterogeneous nature, and a series of tests conducted indicated a degree of publication bias. No significant change in SICI and ICF was observed, with exception to decrease in SICI with cTBS at the early time point (SMD=0.42, P=0.00036). The results also highlight several factors contributing to TBS efficacy, including the number of pulses, frequency of stimulation and BDNF polymorphisms. Further research investigating optimal TBS stimulation parameters, particularly for iTBS, is needed in order for these paradigms to be successfully translated into clinical settings. PMID- 26850211 TI - The neurobiological basis of binge-eating disorder. AB - Relatively little is known about the neuropathophysiology of binge-eating disorder (BED). Here, the evidence from neuroimaging, neurocognitive, genetics, and animal studies are reviewed to synthesize our current understanding of the pathophysiology of BED. Binge-eating disorder may be conceptualized as an impulsive/compulsive disorder, with altered reward sensitivity and food-related attentional biases. Neuroimaging studies suggest there are corticostriatal circuitry alterations in BED similar to those observed in substance abuse, including altered function of prefrontal, insular, and orbitofrontal cortices and the striatum. Human genetics and animal studies suggest that there are changes in neurotransmitter networks, including dopaminergic and opioidergic systems, associated with binge-eating behaviors. Overall, the current evidence suggests that BED may be related to maladaptation of the corticostriatal circuitry regulating motivation and impulse control similar to that found in other impulsive/compulsive disorders. Further studies are needed to understand the genetics of BED and how neurotransmitter activity and neurocircuitry function are altered in BED and how pharmacotherapies may influence these systems to reduce BED symptoms. PMID- 26850212 TI - Effect of electroconvulsive seizures on cognitive flexibility. AB - Electroconvulsive seizures (ECS), an animal model of electroconvulsive therapy, strongly stimulate hippocampal neurogenesis, but it is not known how this relates to the therapeutic effect or to the unwanted cognitive side effects. Recent findings suggest that neurogenesis might be important for flexible learning in changing environments. We hypothesize that animals receiving ECS treatment, which induces hippocampal neurogenesis, will show enhanced cognitive flexibility compared with controls. We have utilized a touch screen-based cognitive test (location discrimination (LD) task) to assess how five consecutive ECS treatments affect cognitive flexibility (measured as reversal of cognitive strategy) as well as spatial pattern separation ability. ECS-treated animals performed more reversals in the LD task earlier than controls over the 9 experimental weeks irrespective of spatial separation of visual stimuli, indicating an enhanced cognitive flexibility but unaffected pattern separation ability after ECS. We observed no correlation between hippocampal neurogenesis and the number of performed reversals during the last experimental week. This is the first study to elucidate the effect of ECS on cognitive flexibility. Our results indicate that ECS improves cognitive flexibility without affecting spatial pattern separation ability. Whether cognitive flexibility is enhanced via neurogenesis or other ECS modulated processes, remains unknown. (c) 2016 Wiley Periodicals, Inc. PMID- 26850213 TI - [General characteristics of psychiatric emergencies in the Mahdia hospital]. PMID- 26850214 TI - [Psychiatric aspects of rheumatoid arthritis: Review of literature]. AB - BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory degenerative disease whose symptoms are mainly joint with significant functional impact, resulting in a restriction of the activities of the patient and increasing the impact on mental well-being. Several studies have been conducted to explore psychiatric disorders comorbid with RA. OBJECTIVE: The objective of this review is to present the various psychiatric manifestations of RA reported in the medical literature. METHODS: A literature review was conducted using the Pubmed search with the following keywords: psychiatry, psychiatric manifestations, rheumatoid arthritis. Three hundred and sixty-one articles were reviewed for relevance and 47 references were selected. RESULTS: Among the major psychiatric disorders found in RA, the anxiety and depressive disorders are prevalent (13 to 48% of patients), as well as suicide, insomnia and tiredness. The impairment of quality of life is markedly after age 65. The association between RA and schizophrenia seems negative so that factors predisposing one is protective for the other. CONCLUSION: Comorbid psychiatric disorders with RA are prevalent and may increase the impairment of quality of life for patients. The detection and treatment of psychiatric disorders improve the care of patients with RA. PMID- 26850215 TI - Clinical Features and Survival of Patients With Follicular Lymphoma in Korea. AB - BACKGROUND: The incidence of follicular lymphoma (FL) varies according to geographic location. It is the second most common non-Hodgkin lymphoma in Western countries but has a very low incidence in Asia. Thus, no representative data are available for FL. Therefore, we gathered our own data to build a foundation for FL research. PATIENTS AND METHODS: We collected a total of 343 patient records. The median age was 53 years, and the ratio of male to female patients was 1.4:1. Most patients received chemotherapy with or without rituximab. RESULTS: The incidence of grade 1 and 2 FL was 64.9% (n = 205) and of stage III and IV was 51.2% (n = 171). The grade tended to be higher and the stage to be lower compared with Western data. In the chemotherapy group, the complete response rate was 76.0%, and the partial response rate was 17.1%. The median follow-up duration was 38.1 months. The estimated 5- and 10-year progression-free survival and overall survival rates were 68.3% and 84.9% and 63.0% and 71.3%, respectively. CONCLUSION: We could not find definitive differences between our Korean data and the Western data, although we found some trends in the baseline characteristics. Therefore, we hope to develop an understanding of FL and perform more qualitative studies in the future. PMID- 26850217 TI - Medicare issues clarifications to "incident to" billing rules. PMID- 26850216 TI - Differences in screening vs non-screening colonoscopy: scope for improvement? AB - AIM: Colonoscopy performed as part of the NHS Bowel Cancer Screening Programme (BCSP) is of high standard as measured using global rating scale (GRS) criteria. Screening practitioners also provide a non-screening colonoscopy service. The current study compares colonoscopy quality indicators between screening and non screening groups performed by a single practitioner using the GRS. METHOD: Patient details were obtained for all consecutive colonoscopies between 2007 and 2014 performed by a single screening practitioner. Data were collected retrospectively from electronic patient records; BCSP Exeter database and non screening colonoscopies were compared. Data included patient demographics (age, gender), sedation, and the GRS data including caecal intubation, adenoma and neoplasia detection rates. RESULTS: In all, 1961 colonoscopy procedures (1067 screening and 894 non-screening) were identified; 57% were men. Mean (SD) age for all patients was 64 (+/- 10.4) years. Non-screening patients were younger [62 (+/ 14) vs 66 (+/- 4.8) years; P < 0.05] and were less likely to be men (51.5% vs 61.9%; P < 0.05) than their screening counterparts. Caecal intubation was more successful in screening patients [1027/1067 (96.3%)] than non-screening patients [805/894 (90%)]; P < 0.05. Adenoma detection rate was higher in the screening (46.8 +/- 4.4) than non-screening (26.3 +/- 11.8) group; P < 0.05. There were no differences in neoplasia detection. Polypectomy was more likely (55.5% vs 30.2%) and polyp retrieval more successful (97.5% vs 86.7%) in the screening group. CONCLUSION: Screening and non-screening colonoscopy differ in the GRS domains of completion and pathology detection. These differences need to be acknowledged when comparing screeners and non-screeners using GRS within units. PMID- 26850218 TI - Care transitions across the continuum: Improving geriatric competence. PMID- 26850219 TI - RNA Structure Duplications and Flavivirus Host Adaptation. AB - Flaviviruses include a highly diverse group of arboviruses with a global distribution and a high human disease burden. Most flaviviruses cycle between insects and vertebrate hosts; thus, they are obligated to use different cellular machinery for their replication and mount different mechanisms to evade specific antiviral responses. In addition to coding for viral proteins, the viral genome contains signals in RNA structures that govern the amplification of viral components and participate in triggering or evading antiviral responses. In this review, we focused on new information about host-specific functions of RNA structures present in the 3' untranslated region (3' UTR) of flavivirus genomes. Models and conservation patterns of RNA elements of distinct flavivirus ecological groups are revised. An intriguing feature of the 3' UTR of insect borne flavivirus genomes is the conservation of complex RNA structure duplications. Here, we discuss new hypotheses of how these RNA elements specialize for replication in vertebrate and invertebrate hosts, and present new ideas associating the significance of RNA structure duplication, small subgenomic flavivirus RNA formation, and host adaptation. PMID- 26850220 TI - Aryl-aryl interactions in designed peptide folds: Spectroscopic characteristics and optimal placement for structure stabilization. AB - We have extended our studies of Trp/Trp to other Aryl/Aryl through-space interactions that stabilize hairpins and other small polypeptide folds. Herein we detail the NMR and CD spectroscopic features of these types of interactions. NMR data remains the best diagnostic for characterizing the common T-shape orientation. Designated as an edge-to-face (EtF or FtE) interaction, large ring current shifts are produced at the edge aryl ring hydrogens and, in most cases, large exciton couplets appear in the far UV circular dichroic (CD) spectrum. The preference for the face aryl in FtE clusters is W ? Y >= F (there are some exceptions in the Y/F order); this sequence corresponds to the order of fold stability enhancement and always predicts the amplitude of the lower energy feature of the exciton couplet in the CD spectrum. The CD spectra for FtE W/W, W/Y, Y/W, and Y/Y pairs all include an intense feature at 225-232 nm. An additional couplet feature seen for W/Y, W/F, Y/Y, and F/Y clusters, is a negative feature at 197-200 nm. Tyr/Tyr (as well as F/Y and F/F) interactions produce much smaller exciton couplet amplitudes. The Trp-cage fold was employed to search for the CD effects of other Trp/Trp and Trp/Tyr cluster geometries: several were identified. In this account, we provide additional examples of the application of cross-strand aryl/aryl clusters for the design of stable beta sheet models and a scale of fold stability increments associated with all possible FtE Ar/Ar clusters in several structural contexts. (c) 2016 Wiley Periodicals, Inc. Biopolymers 105: 337-356, 2016. PMID- 26850221 TI - Atrioventricular conduction disturbances immediately after hepatic graft reperfusion and their outcomes in patients undergoing liver transplantation. AB - Hemodynamic perturbation during hepatic graft reperfusion in patients undergoing liver transplantation (LT) is challenging and is frequently accompanied by bradyarrhythmia and even asystole. However, detailed data on electrocardiographic (ECG) changes during reperfusion are almost nonexistent, although the correct diagnosis by record is important for the treatment. We aimed to identify ECG rhythm disturbances during graft reperfusion and to investigate risk factors and outcomes. Data from 1065 consecutive patients who underwent adult LT were analyzed. The incidence, type, and detailed characteristics of ECG changes immediately after graft reperfusion were assessed using an electronically archived intraoperative ECG database. We analyzed risk factors, postoperative outcomes including major cardiovascular events, 30-day and 1-year mortalities of recipients based on the occurrence of atrioventricular (AV) block, and asystole during reperfusion. The typical pattern of postreperfusion bradyarrhythmia was progressive PR interval prolongation until a Mobitz type 1 AV block occurred. The overall incidence of AV block was 5.0% (53/1065), and 30.2% of them (16/53) had initiated as AV block and then progressed into ventricular asystole. Fulminant hepatic failure was a significant predictor for occurrence of AV block (odds ratio [OR], 7.20; 95% confidence interval, 3.38-15.32; P < 0.001). Patients with AV block showed significantly higher incidence of postoperative major cardiovascular events (P < 0.001) and 30-day mortality (P = 0.002) than those without AV block, whereas the 1-year mortality was not different between the 2 groups (P = 0.10). The postreperfusion asystole was consistently preceded by a Mobitz type 1 AV block. The occurrence of AV block and asystole appears to be an important prognosticator. Therefore, maintaining an optimal range of physiological status and gradual unclamping of the vena cava to avoid sudden atrial distension are recommended in high-risk patients during reperfusion period. Liver Transplantation 22 956-967 2016 AASLD. PMID- 26850222 TI - Efficacy of a therapeutic treatment using gas-filled microbubble-associated phospholipase A2 in a mouse model of honeybee venom allergy. AB - BACKGROUND: Venom immunotherapy is efficient to desensitize people suffering from insect sting allergies. However, the numerous injections required over several years and important risks of severe side reactions complicate the widespread use of immunotherapy. In the search for novel approaches to blunt the overwhelming pro-allergic Th2 response, we evaluated the therapeutic efficacy of a treatment based on a denatured form of the major allergen, phospholipase A2, associated with microbubbles (PLA2denat -MB) in a mouse model of honeybee venom allergy. METHODS: Antibodies measured by ELISA, T-cell responses assessed by CFSE-based proliferation assays and ELISA, and basophil degranulation were examined after PLA2denat -MB-based therapeutic treatment of sensitized mice. Mice were challenged with a lethal dose of PLA2 to evaluate protection against anaphylaxis. RESULTS: Therapeutic subcutaneous administration of two different PLA2denat -MB formulations, in contrast to PLA2denat alone, reduced allergic symptoms and protected all mice from anaphylaxis-mediated death after allergen challenge. At the functional level, the use of PLA2denat decreased IgE-mediated basophil degranulation as compared to the native form of the allergen. In comparison with PLA2denat alone, both PLA2denat -MB formulations decreased allergen-specific Th2 CD4 T-cell reactivity. At the mechanistic level, PLA2denat -MB containing 20% palmitic acid and PEG induced PLA2-specific IgA and increased Foxp3(+) Treg frequencies and TGF-beta production, whereas the formulation bearing 80% palmitic acid triggered the production of IFN-gamma, IgG2a, and IgG3. CONCLUSIONS: In contrast to conventional PLA2 subcutaneous immunotherapy, the therapeutic administration of PLA2-MB treatment to mice that already had established allergy to PLA2 protects all subsequently challenged animals. PMID- 26850223 TI - Comprehensive analysis of cytokine gene polymorphisms defines the association of IL-12 gene with ophthalmopthy in Korean children with autoimmune thyroid disease. AB - In early onset autoimmune thyroid disease (AITD) showing a strong genetic tendency, cytokines have been suggested to play a critical role in the development of AITD. To directly compare the influences of several cytokine gene polymorphisms, 25 single nucleotide polymorphisms (SNPs) in 17 cytokine genes were analyzed on 104 Korean children with AITD [Hashimoto's disease (HD) = 44, Graves' disease (GD) = 60 (thyroid-associated ophthalmopathy (TAO) = 29, non-TAO = 31)] and 192 controls. Compared with healthy controls, any significant association with polymorphisms of cytokine genes was not found in HD and GD. Among GD patients, non-TAO group only showed significant associations with IL-12 C allele (rs3212227: A > C) (76.6% vs. 51.6%, OR = 0.3 [0.15-0.71], Pc = 0.007). Particularly, the frequency of IL-12C allele was significantly lower in the non TAO group than in the TAO group (82.8% vs. 51.6%, Pc = 0.018). Our comprehensive analysis of cytokine gene polymorphisms suggests that IL-12 gene may play impact on specific pathogenesis of ophthalmopathy in Korean children with AITD. PMID- 26850224 TI - A long-term high-fat, high-sucrose diet in Bama minipigs promotes lipid deposition and amyotrophy by up-regulating the myostatin pathway. AB - Skeletal muscle is as an important regulator of blood glucose and glycolipid metabolism and is closely related to motor ability. The underlying mechanisms by which dietary ectopic lipids in skeletal muscle prevents muscle growth remain elusive. We utilized miniature Bama swine as a model to mimic human obesity using prolonged dietary induction. After 23 months on a high-fat, high-sucrose diet, metabolic disorders were induced in the animals, which exhibited increased body weight, extensive lipid deposition in the skeletal muscle and amyotrophy. Microarray profiles demonstrated the up-regulation of genes related to fat deposition and muscle growth inhibition. We outline a clear potential pathway that in combination with increased 11beta-hydroxysteroid dehydrogenase type 1, promotes expression of a major inhibitor, myostatin, by converting corticosterone to cortisol, which leads to the growth inhibition of skeletal muscle. This research provides new insights into the treatment of muscle diseases induced by obesity. PMID- 26850225 TI - Clinical characteristics of primary gastric lymphoma detected during screening for gastric cancer in Korea. AB - BACKGROUND AND AIM: The role of screening endoscopy in primary gastric lymphoma (PGL) has not been investigated. This study aimed to evaluate the clinical characteristics and outcomes of PGLs detected by screening endoscopy in the high prevalence area of Helicobacter pylori (H. pylori) infection. METHODS: This retrospective cohort study enrolled consecutive subjects who were diagnosed with PGL by endoscopic screening in Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea, between October 2003 and September 2013. The characteristics and outcome of screening-detected patients (screening group) were compared with consecutive subjects diagnosed with PGL in the outpatient clinic (outpatient group). RESULTS: Of the 105 194 recipients of screening upper endoscopy, 52 (0.049%) were found to have PGL. The median age was 54.2 years (range 23-79), and 65.4% were women. The proportion of PGL to gastric malignancy was 12.1% (52/429) overall, but >30% (25/73) in middle-aged (40-59) women. PGLs in the screening group were more likely to be mucosa-associated lymphoid tissue lymphoma (98.1% vs 60.0%, P < 0.001) and treated with H. pylori eradication alone (90.0% vs 48.1%, P < 0.001) than those in the outpatient group. Moreover, the screening group showed better 5-year overall survival (100.0% vs 89.3%, P = 0.016) and progression-free survival (94.9% vs 83.4%, P = 0.040) than the outpatient group. CONCLUSIONS: In Korea, a high prevalence area of H. pylori infection, PGL seems more prevalent than in Western countries. Endoscopic screening may help to detect early stage H. pylori-positive mucosa-associated lymphoid tissue lymphoma. A high index of suspicion is needed, especially in middle-aged women. PMID- 26850226 TI - Click Reaction on Solid Phase Enables High Fidelity Synthesis of Nucleobase Modified DNA. AB - The post-synthetic functionalization of nucleic acids via click chemistry (CuAAC) has seen tremendous implementation, extending the applicability of nucleobase modified nucleic acids in fields like fluorescent labeling, nanotechnology, and in vitro selection. However, the production of large quantities of high-density functionalized material via solid phase synthesis has been hampered by oxidative by-product formation associated with the alkaline workup conditions. Herein, we describe a rapid and cost-effective protocol for the high fidelity large-scale production of nucleobase-modified nucleic acids, exemplified with a recently described nucleobase-modified aptamer. PMID- 26850227 TI - Acylated and unacylated ghrelin during OGTT in Prader-Willi syndrome: support for normal response to food intake. AB - BACKGROUND: Prader-Willi syndrome (PWS) is characterized by hyperphagia with impaired satiety. PWS patients have very high acylated ghrelin (AG) with normal unacylated ghrelin (UAG) levels, resulting in an elevated AG/UAG ratio, suggesting an intrinsic defect in the ghrelin regulation. Normally, food intake induces satiety and a drop in AG and UAG levels, but it is unknown if these levels also decline in PWS. OBJECTIVE: To evaluate whether the high AG levels in PWS decline in response to glucose intake during an oral glucose tolerance test (OGTT), and to investigate the effects of growth hormone (GH) treatment on this response. METHOD: Serum levels of AG, UAG and AG/UAG ratio during an OGTT were determined in 24 GH-treated patients with PWS (median age 19.0, range 14.2-25.9 years) and in 10 GH-stop patients (of whom five were in GH-treated group; 18.5, 14.5-20.3 years). RESULTS: In GH-treated and GH-stop young adults with PWS, there was a sharp decline of AG levels and a decrease of UAG levels in the first 30 min after the glucose load, which resulted in a lower AG/UAG ratio. GH-treated patients had significantly lower AG levels than GH-stop patients at baseline and during the OGTT. All UAG levels and AG/UAG ratios were lower in the GH-treated patients, although not significantly. CONCLUSIONS: In young adults with PWS, an oral glucose load significantly reduces AG and UAG levels, suggesting normal regulation of the ghrelin axis by food intake. GH treatment results in lower AG levels at baseline and during OGTT, suggesting a more favourable metabolic profile. Our findings might suggest that the impaired satiety is not the result of an abnormal response of the orexigenic ghrelin to food intake. PMID- 26850228 TI - Molecular docking and simulation studies of 3-(1-chloropiperidin-4-yl)-6-fluoro benzisoxazole 2 against VP26 and VP28 proteins of white spot syndrome virus. AB - White spot syndrome virus (WSSV), an aquatic virus infecting shrimps and other crustaceans, is widely distributed in Asian subcontinents including India. The infection has led to a serious economic loss in shrimp farming. The WSSV genome is approximately 300 kb and codes for several proteins mediating the infection. The envelope proteins VP26 and VP28 play a major role in infection process and also in the interaction with the host cells. A comprehensive study on the viral proteins leading to the development of safe and potent antiviral therapeutic is of adverse need. The novel synthesized compound 3-(1-chloropiperidin-4-yl)-6 fluoro benzisoxazole 2 is proved to have potent antiviral activity against WSSV. The compound antiviral activity is validated in freshwater crabs (Paratelphusa hydrodomous). An in silico molecular docking and simulation analysis of the envelope proteins VP26 and VP28 with the ligand 3-(1-chloropiperidin-4-yl)-6 fluoro benzisoxazole 2 are carried out. The docking analysis reveals that the polar amino acids in the pore region of the envelope proteins were involved in the ligand binding. The influence of the ligand binding on the proteins is validated by the molecular dynamics and simulation study. These in silico approaches together demonstrate the ligand's efficiency in preventing the trimers from exhibiting their physiological function. PMID- 26850229 TI - Erratum to: Dynamics of gene silencing during X inactivation using allele specific RNA-seq. PMID- 26850230 TI - Adapting the Patient-centered Specialty Practice Model for Populations With Cirrhosis. PMID- 26850231 TI - Olfactory pathway of the hornet Vespa velutina: New insights into the evolution of the hymenopteran antennal lobe. AB - In the course of evolution, eusociality has appeared several times independently in Hymenoptera, within different families such as Apidae (bees), Formicidae (ants), and Vespidae (wasps and hornets), among others. The complex social organization of eusocial Hymenoptera relies on sophisticated olfactory communication systems. Whereas the olfactory systems of several bee and ant species have been well characterized, very little information is as yet available in Vespidae, although this family represents a highly successful insect group, displaying a wide range of life styles from solitary to eusocial. Using fluorescent labeling, confocal microscopy, and 3D reconstructions, we investigated the organization of the olfactory pathway in queens, workers, and males of the eusocial hornet Vespa velutina. First, we found that caste and sex dimorphism is weakly pronounced in hornets, with regard to both whole-brain morphology and antennal lobe organization, although several male-specific macroglomeruli are present. The V. velutina antennal lobe contains approximately 265 glomeruli (in females), grouped in nine conspicuous clusters formed by afferent tract subdivisions. As in bees and ants, hornets display a dual olfactory pathway, with two major efferent tracts, the medial and the lateral antennal lobe tracts (m- and l-ALT), separately arborizing two antennal lobe hemilobes and projecting to partially different regions of higher order olfactory centers. Finally, we found remarkable anatomical similarities in the glomerular cluster organizations among hornets, ants, and bees, suggesting the possible existence of homologies in the olfactory pathways of these eusocial Hymenoptera. We propose a common framework for describing AL compartmentalization across Hymenoptera and discuss possible evolutionary scenarios. J. Comp. Neurol. 524:2335-2359, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26850233 TI - [Large prospective cohort studies: a review and update]. PMID- 26850232 TI - Direct Versus Video Laryngoscopy Using the C-MAC for Tracheal Intubation in the Emergency Department, a Randomized Controlled Trial. AB - BACKGROUND: Direct laryngoscopy (DL) has long been the most common approach for emergency endotracheal intubation, although the use of video laryngoscopy (VL) is becoming more widespread. Current observational data suggest that VL has higher first-pass success, although randomized trials are lacking. OBJECTIVES: The objective was to compare first-pass success in patients undergoing emergency intubation with DL or VL using a C-MAC device. METHODS: This was an open-label, prospective, randomized, controlled trial in an academic emergency department of patients undergoing emergency intubation with a plan of DL for the first attempt. Patients were randomly assigned in a 1:1 ratio to either DL or VL using a C-MAC device for the first intubation attempt. The primary outcome was first-pass success. Secondary outcomes included time to intubation, development of aspiration pneumonia, and hospital length of stay (LOS). The study was registered at Clinicaltrials.gov, number NCT01710891. RESULTS: A total of 198 patients were enrolled and intubated with either DL (n = 95) or VL (n = 103). First-attempt success was 86 and 92% for the DL and VL groups, respectively (difference = 5.9%, 95% confidence interval = -14.5% to 2.7%, p = 0.18). Time to intubation, rates of aspiration pneumonia, and hospital LOS were not different between the two groups. CONCLUSIONS: In patients undergoing emergency intubation in whom DL was planned for the first attempt, we did not detect a difference between VL or DL using the C-MAC device in first-pass success, duration of intubation attempt, aspiration pneumonia, or hospital LOS. PMID- 26850234 TI - [Regional specific differences in prevalence of overweight/obesity in China: findings from China Kadoorie Biobank study in 10 areas in China]. AB - OBJECTIVE: To describe gender and regional differences in the prevalence of overweight/obesity in adults found by China Kadoorie Biobank (CKB) study, involving 512 489 adults, in 10 areas in China. METHODS: The baseline survey of CKB was conducted in 5 urban areas and 5 rural areas in China during 2004-2008. After excluding those with extreme value of BMI (<15.0 kg/m(2) or >50 kg/m(2)), 512 489 subjects were included in the analysis. Overweight/obesity was classified according to BMI and WC, and diagnosed according to the guideline for prevention and control of overweight/obesity in Chinese adults. The gender and regional specific distributions of overweight/obesity were compared after adjusting for age. RESULTS: The overall prevalence of overweight/obesity was higher in females (45.3%) than in males (41.7%), and the prevalence of central obesity was also higher in females (44.6%) than in males (38.3%). Both the prevalence of overweight/obesity (66.9% in males and 67.5% in females) and the central obesity (63.3% in males and 64.9% in females) were highest in Qingdao. The area specific difference in the prevalence was more obvious in males than in females. Rural areas all had the low prevalence except Henan. Moreover, central obesity was diagnosed in some subjects (15.3% in females, 9.8% in males) with normal/low BMI (<24.0 kg/m(2)). This phenomenon was more obvious in Qingdao (22.2% in males and 23.2% in females). CONCLUSION: The prevalence of overweight/obesity in adults varied greatly across different areas in China. PMID- 26850235 TI - [Regional differences in adults' tea drinking pattern: findings from China Kadoorie Biobank study in 10 areas in China]. AB - OBJECTIVE: To describe the gender and regional differences in adults' tea drinking pattern found in China Kadoorie Biobank (CKB) survey, involving half million adults, in 10 areas in China. METHODS: The baseline survey of CKB was conducted in 5 urban areas and 5 rural areas in China during 2004-2008. The information on tea drinking of 512 891 adults aged 30-79 years was collected and analyzed. RESULTS: The overall prevalence of regular tea drinking (i.e., weekly) was 50.7% in males and 21.3% in females. Among 10 areas, Hunan reported the highest regular tea drinking prevalence (74.3% in males, 76.6% in females), while Henan reported the lowest regular tea drinking prevalence (5.5% in males, 1.0% in females). Most regular tea drinkers consumed green tea except those from Zhejiang and Haikou. Hunan reported the highest tea consumption per time (3.8 g in males, 3.1 g in females), per day (6.2 g in males, 4.1 g in females) and per week (38.4 g in males, 25.0 g in females). CONCLUSION: The adults' tea drinking pattern i.e. frequency, type, amount of tea and preferred concentration of tea water, varied greatly among the 10 regions covered by CKB study. PMID- 26850236 TI - [Regional differences in adults' smoking pattern: findings from China Kadoorie Biobank study in 10 areas in China]. AB - OBJECTIVE: To describe the regional differences in adults' smoking pattern found by China Kadoorie Biobank (CKB) study involving half million adults in 10 areas in China. METHODS: After exclusion of the adults with self reported histories of coronary heart disease, stroke, cancer and chronic obstructive pulmonary disease at baseline survey, the area specific differences in smoking pattern of 452 829 subjects aged 30-79 years was analyzed. RESULTS: The overall rate of current smoker was higher in males (64.2%) than in females (2.1%). For females, the current smoker rate was higher in Harbin (10.5%) and Sichuan (8.5%) than in other areas. For males, the current smoker rate and the average numbers of cigarettes smoked per day were high in Hunan (68.8%, 20.9) and Sichuan (67.2%, 21.5) ; the current smoker rate was lowest (49.9%) but the average number of cigarettes smoked per day was highest (21.9) in Haikou. On the other hand, Gansu showed the highest rate of current smoker (71.4% ) with a lower mean number of cigarettes smoked per day (14.9). Most current smokers in males (88.3% ) smoked filter cigarettes, while hand-rolled cigarettes were commonly used in Sichuan (38.8%) and Gansu (37.8%) and pipes or water pipe were mainly used in Henan (14.6%). CONCLUSION: The rate of current smoker and other patterns of smoking including cigarette type, daily amount and inhalation depth varied greatly among the adults in 10 areas covered by CKB study. PMID- 26850237 TI - [Area specific differences in lung function indices and prevalence of airflow obstruction in adults: findings from people in 10 areas in China]. AB - OBJECTIVE: To describe the area specific differences in lung function indices and prevalence of airflow obstruction (AFO) in adults found by China Kadoorie Biobank (CKB) study, involving 512 495 adults, in 10 areas in China. METHODS: The detailed information on lung function indices (FEV, and FVC) and prevalence of AFO (diagnosed according to GOLD and LLN criteria) of subjects aged 30-79 years were analyzed, those with abnormal lung function indices at baseline survey were excluded. RESULTS: The FEV1 and FVC among males (2.66 L, 3.16 L) were higher than those among females (1.99 L, 2.35 L). The FEV1 and FVC were highest in Henan and Harbin. The prevalence of AFO diaonosed according to GOLD criteria was 5.13% in males, higher than that in females (3.75%). The prevalence of AFO was higher in rural area than in urban area (males: 6.32% vs. 3.47%; females: 4.26% vs. 2.97%). The prevalence of AFO was highest in Sichuan (13.34% in males, 10.70% in females), followed by that in Suzhou, Henan and Hunan. The prevalence of AFO diagnosed according to LLN criteria (6.93% in males, 6.29% in females) was higher than that diagnosed according to GOLD criteria, but the area specific difference was similar. CONCLUSION: The lung function indices and the prevalence of AFO in adults varied greatly among the 10 areas covered by CKB study. PMID- 26850238 TI - [Association between sleep duration and stroke in adults]. AB - OBJECTIVE: To explore the association between sleep duration and stroke in adults. METHODS: Baseline data of 57 704 subjects who were aged 30-79 years and enrolled into China Kadoorie Biobank (CKB) study from Tongxiang county, Zhejiang province were analyzed. Multiple logistic regression analysis was conducted to investigate the putative association between sleep duration and stroke after adjusting for potential confounders. RESULTS: The mean age of the subjects was (53.15 +/- 10.20) years in males and (51.72 +/- .69) years in females, respectively. There were 14.43% of males and 15.30% of females reporting sleep durations <= 6 hours per day and 5.39% of males and 5.95% of females reporting long duration of sleep (>= 10 hours per day). The prevalence of stroke was 0.92% in males compared with 0.44% in females. The prevalence of stroke showed a U shaped distribution with sleep duration. Compared with 7 hours sleep duration per day, long sleep duration (>= 10 hours per day) was associated with stroke. The odds ratios (OR) were 2.11 (95%CI: 1.32-3.37) for males and 2.13 (95%CI: 1.24 3.65) for females after adjusting for age, socioeconomic status, health behaviors and health status. No statistical significant association was found between short sleep duration and stroke. Meanwhile, frequent sleep snoring was found to be associated with stroke in females (OR=1.63, 95% CI: 1.11-2.40). CONCLUSION: Longer sleep duration was found to be associated with higher risk of stroke in both males and females. Frequent sleep snoring would increase the risk of stroke in females. PMID- 26850239 TI - [Characteristics of hypertension prevalence and related factors in rural area in Sichuan]. AB - OBJECTIVE: To understand the prevalence, awareness, treatment and control of hypertension in rural area in Sichuan province. METHODS: The cross-sectional data of 55 687 subjects who were enrolled into the China Kadoorie Biobank study from Pengzhou in southwestern China were used to analyze the prevalence, awareness, treatment and control of hypertension among local residents. RESULTS: The prevalence of hypertension among population aged 30-79 years old was 25.2%. The awareness rate of self hypertension status, the treatment rate and the control rate of hypertension were 24.7%, 14.7% and 3.7%, respectively. The prevalence of hypertension, the awareness rate of self hypertension status, the treatment rate and the control rate of hypertension were associated with the socio-demographic characteristics of the subjects. The prevalence of hypertension in winter (70% 80%) was higher than that in summer, while the awareness rate, the treatment rate and the control rate of hypertension in winter were much lower than those in summer. Among the hypertension patients, the rates of smoking and alcohol use were high, the dietary habit was bad, physical activities were less and the prevalence of obesity was higher. The lifestyles of the hypertension patients were improved in those who know about their disease status. CONCLUSION: The prevalence of hypertension was high, but the awareness rate of self hypertension status, the treatment rate and the control rate of hypertension were low in rural area in Sichuan. It is necessary to strengthen the health education in young population and the treatment and control of hypertension in old population. Meanwhile, the management of hypertension patients should be standardized. PMID- 26850241 TI - [Effect of comprehensive intervention on capacity in prevention and control of chronic diseases in community medical staff in Hangzhou]. AB - OBJECTIVE: To evaluate the effect of the Oxford Health Alliance-Community Interventions for Health on chronic diseases prevention and control capacity in community medical staff in Hangzhou. METHODS: A two year comprehensive intervention on chronic disease prevention and control capacity was conducted in the medical staff in Xiacheng district and Gongshu district, Xihu district was used as control according to the study design principal of parallel comparison and non-random grouping. The intervention effect was evaluated with Cochran Mantel-Haenszel test. A total of 985 questionnaires were completed in the baseline survey and 870 questionnaires were completed in the follow-up survey. RESULTS: After 2 year intervention, the detection rates of blood cholesterol, blood pressure and fasting blood glucose by community medical staff significantly increased compared with the rates before the intervention (chi2 =7.97, P =0.05 ; chi2 =27.21, P =0.00 ; chi2 =21.32, P=0.00). While, in the control district, the fasting blood glucose detection rate increased from 25.37% to 31.19%, the differences showed statistical significance (chi2 =15.29, P=0.00). The communication between community medical staff and patients about healthy diet pattern was improved after the intervention, the difference was statistical significant (chi2 =8.64, P=0.03). However, no significant differences in communication about increasing physical activity and smoking cessation between community medical staff and patients was found before and after intervention both in intervention districts and in control district. Furthermore, multivariate logistic regression analysis indicated that the interventions on screening of common chronic diseases and management of chronic diseases patients were related with the detections of blood cholesterol, blood pressure and fasting blood glucose. Moreover, the intervention on counsel and suggestion for chronic disease prevention and control had some influence on the communication about chronic disease risk factors between community medical staff and patients. CONCLUSION: The intervention on chronic disease prevention and control capacity in community medical staff was effective to improve the detection of chronic diseases in community and the communication between the medical staff and patients. PMID- 26850240 TI - [Prevalence and associated risk factors of diabetes among ethnic Han residents in Guizhou]. AB - OBJECTIVE: To understand the fast plasma glucose (FPG) level and the epidemiologic characteristics of diabetes in ethnic Han residents of Guizhou province. METHODS: The survey was conducted among the ethnic Han residents aged 20-80 years, who were selected through multi stage cluster sampling in Guizhou. Basic laboratory test, physical examination were performed for each subject. RESULTS: A total of 2 967 subjects were surveyed. The average FPG level was 5.21 mmol/L for urban residents and 5.03 mmol/L for rural residents, (P<0.001) and the average FPG level was higher in males than in females (5.23 mmol/L vs. 5.09 mmol/L, P=0.003). The FPG level increased with age (P<0.001). In urban residents, the standardized prevalence of diabetes was 6.01% (crude prevalence: 7.45%), higher in males than in females (P<0.001) and increased with age. In rural residents, the standardized prevalence of diabetes was 3.47% (crude prevalence: 3.77%) and increased with age, but there was no sex specific difference in diabetes prevalence. The awareness rate of self diabetes status was 56.59%, the treatment rate was 84.47% and the plasma glucose control rate was 41.38%. Multiple logistic regression analysis indicated that risk factors for diabetes included being male, older than 40 years, family history of diabetes, frequent physical exercise, hypertension, high triglycerid level. CONCLUSION: The prevalence of diabetes was high in ethnic Han residents in Guizhou, the differences in diabetes prevalence between urban area and rural area was statistical significant. More than half of the patients' FPG level had not been under control after treatment. The awareness rate of self diabetes status, the treatment rate and the control rate of diabetes should be improved. PMID- 26850242 TI - [Prevalence of tobacco and alcohol use in ethnic Hui and Han residents in Ningxia]. AB - OBJECTIVE: To understand the prevalence of tobacco and alcohol use in ethnic Hui and Han residents in Ningxia Hui autonomous region and provide evidence for the smoking cessation and alcohol use reduction in minority area. METHODS: Face to face interview was performed in 6 476 subjects aged >= 18 years who were selected through systematic sampling in Ningxia. The tobacco use and alcohol use related disorders were evaluated with Composite International Diagnostic Interview 3.0 (CIDI 3.0 ) according to International Classification of Diseases-10 (ICD-10 ). RESULTS: A total of 5 811 subjects completed the survey, the prevalence of current smoking was 19.15%, which was significantly higher in males than in females (44.73% vs. 1.51%, chi2 =1 693.25, P<0.001). The prevalence of current smoking was lower in Hui males than in Han males (33.19% vs. 51.95%, chi2 =79.99, P<0.001). The prevalence of tobacco dependence was 1.75% in males, the difference between Hui ethnic group and Han ethnic group had no statistical significance (chi2 = 0.02, P=0.958). The prevalence of alcohol use was 5.78%, and it was significantly higher in males than in females (12.48% vs. 1.16%), the difference had statistical significance (chi2 =329.94, P<0.001). The prevalence of alcohol use was lower in Hui males than in Han males (4.71% vs. 17.34%), the difference had statistical significance (chi2 =82.03, P<0.001). The prevalence of alcohol use related disorders was 6.03% in males, and it was higher in Han ethnic group than in Hui ethnic group (3.50% vs. 7.61% ), the difference had statistical significance (chi2 =16.68, P<0.001). CONCLUSION: The prevalence of tobacco use and alcohol use were lower in Hui ethnic group than in Han ethnic group in Ningxia, which might be explained by the influence of the tradition of Hui ethnic group. PMID- 26850243 TI - [Cross-section survey on smoking behavior and cognition in Chongqing, 2014]. AB - OBJECTIVE: To investigate the prevalence of smoking, smoking cessation, passive smoking and awareness of the dangers of tobacco in population in Chongqing and provide evidence for developing prevention and control measures. METHODS: A total of 5 400 residents aged >=18 years were selected from 9 districts/counties in Chongqing through stratified multi-stage cluster sampling and face-to-face interviews were conducted among them. Indicators as current smoking rates, smoking cessation rates and passive smoking rates were calculated by the weight of age proportions from 2010 population census. The analytical method was based on complex sampling design. RESULTS: The current smoking rate of the residents aged >=18 years was 27.4% (male: 53.5% and female: 1.1%), which was highest in age group 40-50 years (58.4%) for males. The current smoking rate among rural residents was higher than that in urban residents. The prevalence of daily cigarette smoking was 27.5%, which was significantly higher in southeastern Chongqing. The rate of passive smoking was 52.4%. Among daily smokers, the mean number of cigarettes smoked was 17.5 per day (men: 17.6 per day; women: 13.5 per day). The daily smoked cigarette number in males was higher in age group 40-50 years (20.1 per day) and those with junior middle school education level (18.9 per day). The proportion of the current smokers who smoked more than 20 cigarettes per day (the rate of heavy smoker) was higher in males than in females and in rural residents than in urban residents. The proportion of heavy smokers was 59.3%, which was highest in age group 40-50 years (66.8%), followed by those with junior middle school educational level (65.2%). The average age of smokers when they stared to smoke was 20.8 years old, which was low in males and rural residents. About 80.2% of the smokers stared to smoke under 25 years old, and 70.3% of the smokers stared to smoke between 15 and 25 years old. The overall rate of smoking cessation was 20.1% and the successful smoking cessation rate was 13.7%. The two rates increased with age, the successful smoking cessation rate was lowest in age group 18-40 years (4.8%). The awareness of the tobacco risk related knowledge seemed poor among the residents, only 19.6% of the residents were aware that smoking could cause serious diseases (stoke, heart disease and lung cancer). 21.9% of the residents were aware that passive smoking could cause serious diseases (heart disease, lung disease and lung cancer). CONCLUSION: Current prevalence of smoking in males in Chongqing remains at a high level, indicating that the publicity programs on the tobacco risk related knowledge needs to be strengthened and the tobacco control needs more efforts. The tobacco control in Chongqing is still facing serious challenge. PMID- 26850244 TI - [Incidence of low birth weight among single live birth neonates and influencing factors in Shaanxi]. AB - OBJECTIVE: To analyze the incidence of low birth weight among single live birth neonates and identify the influencing factors in Shaanxi province. METHODS: A questionnaire survey was conducted among the childbearing aged women selected through multi stage stratified random sampling in Shaanxi during 2010-2013, all of these childbearing aged women were in pregnancy or had definite pregnancy outcomes. RESULTS: A total of 28 164 childbearing aged women and their infants were investigated. The overall incidence of low birth weight among the single live birth neonates surveyed was 3.4% during 2010-2013 (4.1% in 2010, 4.4% in 2011, 3.1% in 2012, 2.6% in 2013, respectively). The incidence of the low birth weight was 3.8% in southern Shaanxi, 3.4% in northern Shaanxi and 3.2% in central area of Shaanxi. The incidence of the low birth weight was 2.5% in urban area and 3.6% in rural area. Compared with the low birth weight incidence of 2.6% in full term infant, the low birth weight incidence was 32.0% in preterm infants. The results of logistic regression analysis suggested that being female infant (OR=1.57, 95% CI: 1.36-1.81), preterm delivery (OR=18.28, 95% CI: 15.23-21.96), lower educational level of mothers (OR=1.27, 95% CI: 1.06-1.52), antenatal care times <4 (compared with 4-7, OR=1.36, 95% CI: 1.14-1.63), antenatal care times >= 8 (compared with 4-7, OR=1.84, 95% CI: 1.48-2.29), gestational hypertension (OR=3.07, 95% CI: 2.12-4.43), being multipara (OR=1.21, 95% CI: 1.03-1.41), taking no folic acid during pregnancy (OR=1.30, 95% CI: 1.12-1.52) were risk factors for the low birth weight of neonate. CONCLUSION: The incidence of low birth weight among single live birth neonates was in decline in Shaanxi. The incidence of the low birth weight was higher in rural area than in urban area. The incidence of the low birth weight was lower than national level. Being female neonate, preterm delivery, lower education level of mothers, irregular antenatal care, gestational hypertension, being multipara, taking no folic acid during pregnancy were the risk factors for low birth weight of neonates. PMID- 26850246 TI - [A model for evaluation of key measures for control of chikungunya fever outbreak in China]. AB - OBJECTIVE: To analyze the transmission pattern of Chikungunya (CHIK) fever in community and evaluate the effectiveness of mosquito control, case isolation and other key control measures by using ordinary differential equation (ODE) model. METHODS: According to natural history of CHIK, an ODE model for the epidemiological analysis of CHIK outbreak was established. The key parameters of the model were obtained by fitting the model with reported outbreak data of the first CHIK outbreak in China. Then the outbreak characteristics without intervention, the effectiveness of mosquito control and case isolation were simulated. RESULTS: Without intervention, an imported case would cause an outbreak in a community with population of 11 000, and cumulative case number would exceed 941 when the total attack rate was 8.55%. The results of our simulation revealed that the effectiveness of case isolation was not perfect enough when it was implemented alone. Although the number of cases could be decreased by case isolation, the duration of outbreak would not be shortened. Differently, the effectiveness of mosquito control was remarkable. In addition, the earlier the measure was implemented, the better the effectiveness would be. The effectiveness of mosquito control plus case isolation was same with mosquito control. CONCLUSION: To control a CHIK outbreak, mosquito control is the most recommended measures. However, case isolation is also necessary as the supplementation of mosquito control. PMID- 26850245 TI - [Epidemiology of confirmed and suspected norovirus outbreaks in Shanghai, 2010 2014]. AB - OBJECTIVE: To understand the epidemiologic characteristics of confirmed and suspected norovirus outbreaks in Shanghai during 2010-2014. METHODS: The investigation reports of confirmed and suspected norovirus outbreaks in Shanghai from 2010 to 2014 were analyzed. RESULTS: A total of 80 norovirus outbreaks, involving 2 399 cases, were reported during this period, and the overall attack rate was 4.17%. The median of the outbreak duration was 4.5 days and the incidence peaked 2 days later averagely for an outbreak. The outbreaks mainly occurred in autumn and winter, 53 outbreaks occurred during October-February, accounting for 66.25%. Seventy five outbreaks occurred in schools, child care settings and nursing houses, accounting for 93.75%. The attack rates in hospitalized patients and the elders in nursing houses were higher than those in pre-school and school aged children, the differences were statistically significant (chi2 =683.12, P<0.01). The attack rates in medical staff and nurses in hospitals and nursing houses or staff in pre-schools and schools were lower. Vomiting, the main clinical symptom, occurred in 1 900 cases (79.20%), diarrhea and fever developed in 694 cases (28.93% ) and 364 cases (15.17% ) respectively. The differences were statistically significant (chi2 =2 251.48, P<0.01). The outbreaks were mainly caused by short common exposures and contact with cases. CONCLUSION: The surveillance for norovirus infection should be strengthened in hospitals, schools and others with the crowed during autumn-winter. The protection of risk population should be enhanced. PMID- 26850247 TI - [Spatial temporal distribution of mumps in Gansu, 2009-2013]. AB - OBJECTIVE: To detect the spatial temporal distribution of mumps in Gansu by means of spatial statistics. METHODS: The county-based incidence of mumps from 2009 to 2013 was used to calculate the global Moran's I and local G statistics, and analyze its spatial temporal distribution characteristics. RESULTS: The incidence of mumps in Gansu were spatial auto-correlated from 2009 to 2013 respectively (P<0.001), and the hot spots were mainly distributed in Hexi area, while the cold spots were distributed in Tianshui, Longnan and Qingyang. Spatial temporal analysis showed that the high incidence of mumps was most likely to be detect in Hexi area (RR=3.05, LLR=4 670.995, P<0.001), and the low incidence was most likely to be detect in Longdong area (RR=0.36, LLR=1 980.686, P<0.001). CONCLUSION: The spatial and spatial temporal clustering of mumps existed in Gansu from 2009 to 2013, the results can be used in the development of mumps prevention and control measure in Gansu. PMID- 26850248 TI - [Surveillance for diarrheagenic Escherichia coli in Shanghai, 2012-2013]. AB - OBJECTIVE: To understand the distribution of diarrheagenic Escherichia (E.) coli in population in Shanghai and discuss the practice model of cooperation in enteric infectious disease prevention and control between public health institution and hospital. METHODS: Sentinel hospitals were assigned, standard detection and identification of diarrheagenic E. coli were conducted, incidence curve of diarrheagenic E. coli infection was drawn and epidemiologic survey and laboratory detection were conducted for suspect diarrheagenic E. coli infection outbreaks. RESULTS: A total of 7 204 stool specimens were collected from diarrhea patients in 4 hospitals during 2012-2013, in which 712 (9.9% ) were diarrheagenic E. coli positive, including 351 enteropathogenic E. coli (EPEC) strains, 292 enterotoxigenic E. coli (ETEC) strains, 32 enteroinvasive E. coli(EIEC) strains and 6 Shiga toxin-producing E. coli (STEC/EHEC) strains, as well as 31 mixed strains. EPEC infection mainly occurred in children aged 1-5 years; and all of these infections were caused by aEPEC. The incidence peak of ETEC infection was during August, the positive rate was >20%. The ETEC infection mainly occurred in infants aged 1-28 days in 2012 and in people aged 20-60 years in 2013 (P<0.05). ST was the major type (59.6%), followed by LT (27.8%) and ST/LT (12.6%). EIEC infection increased in children obviously in 2013 (P<0.01). No EHEC O157:H7 case was detected, but two EHEC O26:H11 (eae-hlyA-stx1a) cases in children were reported for the first time in Shanghai. The survey result indicated that the multidrug-resistant ETEC (STh-CS21-CFA/I-ClyA-EatA-ST2332-SHNL0005) strain causing outbreak in 15 newborns in Shanghai in 2012 was in the same clone as the strain detected in Zigong in Sichuan province. CONCLUSION: Significant change has occurred in diarrheagenic E. coli distribution in Shanghai in recent years, ETEC has potential risk to cause outbreak of hospital acquired infection in neonates and food borne infection. The active surveillance on ETEC and other enteric pathogens by both public health institutions and hospitals need to be improved. PMID- 26850249 TI - [Prevalence of hepatitis C virus antibody among newly reported HIV infection cases in Henan, 2012-2014]. AB - OBJECTIVE: To study the prevalence of antibody to hepatitis C virus (anti-HCV) among newly reported HIV infection cases in Henan province, 2012-2014. METHODS: HIV-1 BED incidence test and anti-HCV test were conducted in newly diagnosed HIV infection cases in Henan, which were reported through national AIDS information system between 1 July 2012 and 30 June 2014. RESULTS: The data of 4 267 newly reported HIV-1 infection cases were analyzed, the positive rate of anti-HCV was 13.19% (563/4 267). The anti HCV was highest in those infected with HIV through injection drug use (77.27%), the anti-HCV positive rates in those infected with HIV through blood donation/transfusion, heterosexual contact, homosexual contact and mother-to-child transmission were 15.06%, 15.81%, 3.74% and 8.96%, respectively. Kaifeng (32.04%), Nanyang (14.67%), Shangqiu (25.00%), Zhumadian (25.00%) and Zhoukou (18.86%) were the first five prefectures with the high anti HCV positive rates. The anti-HCV positive rate in BED positive patients (recent HIV-1 infections) was 7.50% (86/1 146). The multivariate logistic regressions analysis revealed that BED negative, aged >40 years, being farmer, HIV infection though injection drug use and living in in Kaifeng, Nanyang, Shangqiu, Zhumadian and Zhoukou were the risk factors for HCV infection. CONCLUSION: The positive rate of anti-HCV declined between 2012-2014 in newly reported HIV infection cases in Henan, but the positive rate of anti-HCV was high in risk population and in some areas. PMID- 26850250 TI - [Analysis on influence of meteorological factors on Oncomelania density]. AB - OBJECTIVE: To understand the influence of meteorological factors on Oncomelania density in natural condition and provide scientific evidence for the control of the spread of schistosomiasis and Oncomelania. METHODS: Based on the Oncomelania survey data in spring and ground meteorological observation data of Qianjiang from 1990 to 2014, the first-order autoregressive analysis method was used for trend fitting and disassemble, and the correlation between the change rate of Oncomelania density and various meteorological factors in different periods were analyzed. RESULTS: The greatest influence of meteorological factors on Oncomelania density was temperature, followed by precipitation. The average minimum temperature in January and from December to February had predominant influence on Oncomelania density and frame occurrence rate of living Oncomelania (FORLO) respectively. The rise (fall) of average minimum temperature in January by 1 degrees C would lead to the increase (decrease) of Oncomelania density by 5.080%-6.710%; The rise (fall) of average minimum temperature from December to February by 1 degrees C would lead to the increase (decrease) of FORLO by 15.521%-15.928%. The period with the biggest influence of precipitation on Oncomelania density was from November to April, as the rainfall declined >20%, drought might occur, which would cause the reduction of Oncomelania density. Sunshine from September to November had some correlations with the change of Oncomelania density and FORLO. Statistical regression models for the change of Oncomelania density, FORLO and meteorological factors based on correlation analysis were established respectively. CONCLUSION: Weed removal in Oncomelania areas before December is beneficial to reduce the surface temperature and soil moisture content, which would result in Oncomelania density reduction in some extent. It' s notable that the winter temperature is in rise in Hubei province along with global climate change, causing the Oncomelania density to increase, to which more attention should be paid. PMID- 26850251 TI - [Burden of disease caused by low body weight in children aged <5 years in China, 1990-2010]. AB - OBJECTIVE: To analyze the disease burden caused by low body weight in children under 5 years old in China from 1990 to 2010. METHODS: The analysis was conducted on the low body weight related deaths, years lived with disability (YLD), years of life lost (YLL) and disability-adjusted life years (DALY) in children aged <5 years in China from 1990 to 2010 by using the data for the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD2010). The annual low body weight related deaths, YLL, YLD and DALY from 1990 to 2010 were compared. RESULTS: Among the children aged <5 years, 2 271 deaths and 295 300 person-years DALY were attributable to low body weight in 2010. Compared with 1990, the number of deaths and DALY attributed to low body weight decreased by 96.75% and 95.46% respectively. In 2010, the YLD and YLL attributable to low body weight in the children aged <5 years were 101 500 person-years and 193 800 person-years respectively. Compared with 1990, the YLD and YLL caused by low body weight in the children aged <5 years declined by 444 800 and 5.76 million person-years respectively. CONCLUSION: Compared with 1990, the death and DALY, YLD and YLL attributable to low body weight in the children aged <5 years significantly declined in 2010. Considering the serious impact of death to loss of life in young age group, the effects and burden of disease caused by low body weight in the children aged <5 years should not be neglected in China. PMID- 26850252 TI - [Etiologic characteristics of food-borne Vibrio parahaemolyticus strains isolated in Guangdong, 2014]. AB - OBJECTIVE: To investigate the serotypes, antimicrobial resistance, virulence genes and molecular characteristics of food-borne Vibrio parahaemolyticus isolated in Guangdong province in 2014. METHODS: Sixty V. parahaemolyticus strains were tested in this study. The serotyping and antibiotic resistance test were conducted, while the tdh and trh gens of the strains were detected with conventional PCR, and pulsed field gel electrophoresis (PFGE) and multiple locus sequence typing (MLST) were conducted too. RESULTS: The 60 strains belonged to 13 serotypes, the major serotypes included O3: K6, O4: K8, O1: K36 and O4: KUT. The antibiotic resistance test indicated the isolates were highly resistant to ampicillin (100.0%), sulfonamides (43.3%) and cefalotin (28.3%). Up to 56.7%(34/60) of the strains were resistant to two or more antibiotics, and 2 strains showed resistance to three antibiotics. The virulence gene detection indicated that 63.3% (38/60) of the strains carried tdh+ trh-, while only 1 strain carried tdh+ trh+. The 60 strains digested by NotI belonged to 48 different PFGE patterns and 3 clusters. The cluster B included the strains isolated from sporadic food borne cases with serotype of O3: K6 and similarity of 62.6%-100.0%. The cluster C included O4: K8 strains with the PFGE pattern similarity of 56.7%-62.5%. The MLST indicated that the 60 strains had 26 sequence types (STs). The ST-3 was predominant, including 33 strains (serotypes O3: K6 and O1 :K36). The four O4: K8 strains formed another predominant colony, which was different from ST-3. CONCLUSION: The etiologic characteristics of V. parahaemolyticus varied, which might be one of the reasons for high incidence of food-borne V. parahaemolyticus infection in Guangdong. The molecular characteristics of O4: K8 strain were different from the other predominant serotypes. Close attention should be paid to the possible outbreak caused by O4: K8 strain in this area. PMID- 26850253 TI - [Study on levels of serum phosphorus, bone alkaline phosphatase and 25 hydroxyvitamin D in preterm infants with very low birth weight]. AB - OBJECTIVE: To compare the levels of serum phosphorus, bone alkaline phosphatase and 25-hydroxyvitamin D3 in preterm infants with very low birth weight, and provide evidence for early screening, prevention of metabolic bone disease in preterm infants. METHODS: A total of 110 newborns who met the inclusion criteria were selected in pediatric ward in our hospital. The case group included 60 preterm infants with very low birth weight and control group included 50 full term infants. Fasting blood were taken from the subjects at week 1, 4, and 12 respectively, and ELISA was conducted to quantitatively detect the serum levels of phosphorus, bone alkaline phosphatase and 25-hydroxyvitamin D. RESULTS: The increase of serum 25-hydroxyvitamin D3in case group was smaller than that in control group; the levels of serum phosphorus had no significant difference between two groups. In case group, the level of bone alkaline phosphatase increased at week 1, 4, and 12, and the 25-hydroxyvitamin D3level had significant difference at week 12 (P<0.05). The abnormal rate of 25-hydroxyvitamin D3 level was 26.7% for case group and 0% for control group. CONCLUSION: There were significant differences between case group and control group in levels of bone alkaline phosphatase and 25-hydroxyvitamin D3, suggesting that detecting the serum levels of bone alkaline phosphatase and 25-hydroxyvitamin D3 would facilitate the early diagnosis of metabolic bone disease in preterm infants. PMID- 26850254 TI - [Meta-analysis on relationship between single nucleotide polymorphism of rs2231142 in ABCG2 gene and gout in East Asian population]. AB - OBJECTIVE: To systematically evaluate the association between single nucleotide polymorphism of rs2231142 genetic susceptibility and gout in East Asian population. METHODS: The literature retrieval was conducted by using English databases (Medline, EMbase), Chinese databases (CNKI, Vip, Wanfang, SinaMed) and others to collect the published papers on the association between single nucleotide polymorphism of rs2231142 genetic susceptibility and gout by the end of December 2014. Meta-analysis was performed with software Stata 12.0. RESULTS: Nine studies were included. There were significant associations between increased risk of gout and single nucleotide polymorphism of rs2231142, the combined OR was 2.04 (95%CI: 1.82-2.28) for A allele and C allele, 1.97 (95%CI: 1.57-2.48) for CA and CC, 3.71 (95%CI: 3.07-4.47) for AA and CC. Sex and region specific subgroup analysis showed less heterogeneity. CONCLUSION: There is significant association between gout and single nucleotide polymorphism of rs2231142 in East Asian population, and A allele is a high risk gene for gout. PMID- 26850255 TI - [Prevalence of HIV infection and syphilis, sexual behaviors and awareness of HIV/AIDS related knowledge among men who have sex with men in China: a Meta analysis of data collected from 2010 to 2013]. AB - OBJECTIVE: To understand the time and area specific prevalence of HIV infection and syphilis, sexual behaviors and awareness of HIV/AIDS related knowledge among men who have sex with men (MSM) in the mainland of China during 2010-2013. METHODS: All the published academic papers on the prevalence of HIV infection and syphilis among MSM in the mainland of China from 2010 to 2013 were collected from CNKI, Wanfang and PubMed databases. Meta-analysis was performed by using software Stata 12.0. RESULTS: Sixty six papers were selected. From 2010 to 2013 the pooled prevalence of HIV infection were 7.7% among the MSM (95% CI: 7.2%-8.3% ) and increased year by year, but the pooled prevalence of HIV infection was highest in southwestern China (12.0%). The pooled prevalence of syphilis were 10.9% among the MSM (95% CI: 9.8%-12.1%), and the pooled prevalence of syphilis was highest in southern China (14.4%). The incidence of anal sex was high (84.2%) in the past 6 months, but the consistent condom use rate was low (44.8%). The AIDS related knowledge awareness was high in the MSM (88.4%). CONCLUSION: The prevalence of HIV infection and syphilis were high among the MSM in the mainland of China during 2010-2013. It is necessary to explore the comprehensive intervention measures to promote condom use among MSM although they have high awareness of AIDS related knowledge. PMID- 26850256 TI - [Detecting gene-gene/environment interactions by model-based multifactor dimensionality reduction]. AB - This paper introduces a method called model-based multifactor dimensionality reduction (MB-MDR), which was firstly proposed by Calle et al., and can be applied for detecting gene-gene or gene-environment interactions in genetic studies. The basic principle and characteristics of MB-MDR as well as the operation in R program are briefly summarized. Besides, the detailed procedure of MB-MDR is illustrated by using example. Compared with classical MDR, MB-MDR has similar principle, which merges multi-locus genotypes into a one-dimensional construct and can be used in the study with small sample size. However, there is some difference between MB-MDR and classical MDR. First, it has higher statistical power than MDR and other MDR in the presence of different noises due to the different way the genotype cells merged. Second, compared with MDR, it can deal with all binary and quantitative traits, adjust marginal effects of factors and confounders. MBMDR could be a useful method in the analyses of gene gene/environment interactions. PMID- 26850257 TI - [Research progress on prevalence and risk factors of HIV among male-to-female transgenders]. PMID- 26850258 TI - [Research progress in mobile phone software for health interventions in men who have sex with men]. PMID- 26850259 TI - [Exploring pathogenic genes of non-syndromic oral cleft in post-GWAS era: from syndromic oral cleft to non-syndromic oral cleft]. PMID- 26850261 TI - The BAH domain of BAHD1 is a histone H3K27me3 reader. PMID- 26850260 TI - Structural dynamics of the yeast Shwachman-Diamond syndrome protein (Sdo1) on the ribosome and its implication in the 60S subunit maturation. AB - The human Shwachman-Diamond syndrome (SDS) is an autosomal recessive disease caused by mutations in a highly conserved ribosome assembly factor SBDS. The functional role of SBDS is to cooperate with another assembly factor, elongation factor 1-like (Efl1), to promote the release of eukaryotic initiation factor 6 (eIF6) from the late-stage cytoplasmic 60S precursors. In the present work, we characterized, both biochemically and structurally, the interaction between the 60S subunit and SBDS protein (Sdo1p) from yeast. Our data show that Sdo1p interacts tightly with the mature 60S subunit in vitro through its domain I and II, and is capable of bridging two 60S subunits to form a stable 2:2 dimer. Structural analysis indicates that Sdo1p bind to the ribosomal P-site, in the proximity of uL16 and uL5, and with direct contact to H69 and H38. The dynamic nature of Sdo1p on the 60S subunit, together with its strategic binding position, suggests a surveillance role of Sdo1p in monitoring the conformational maturation of the ribosomal P-site. Altogether, our data support a conformational signal relay cascade during late-stage 60S maturation, involving uL16, Sdo1p, and Efl1p, which interrogates the functional P-site to control the departure of the anti association factor eIF6. PMID- 26850262 TI - Proximal Roux-en-y Gastrojejunal Anastomosis with Pyloric Ring Resection Improves Gastric Emptying After Pancreaticoduodenectomy. AB - BACKGROUND: Delayed gastric emptying (DGE) is a common complication of pancreaticoduodenectomy. We determined the efficiency of a new reconstruction technique, designed to preserve motilin-secreting cells and maximize the utility of their receptors, in reducing the incidence of DGE after pancreaticoduodenectomy. METHODS: From April 2005 to September 2014, 217 consecutive patients underwent pancreaticoduodenectomy at our institution. Nine patients who underwent total pancreatectomy were excluded. We compared outcomes between patients who underwent pancreaticoduodenectomy with resection of the pyloric ring followed by proximal Roux-en-y gastrojejunal anastomosis (group I, n = 90) and patients who underwent standard pancreaticoduodenectomy with the orthotopic reconstruction technique (group II, n = 118). RESULTS: Overall and clinically relevant rates of DGE were significantly lower in group I than in group II (10 and 2.2 % vs. 57 and 24 %, respectively; p < 0.05). Length of hospital stay as a result of DGE was shorter in group I than in group II. In univariate analysis, older age, comorbidities, ASA grade 4, operative time, preoperative diabetes, standard reconstruction technique, and postoperative complications were significant risk factors for DGE. In multivariate analysis, older age, standard technique, and postoperative complications were independent risk factors for DGE. CONCLUSION: Our new reconstruction technique reduces the occurrence of DGE after pancreaticoduodenectomy. PMID- 26850263 TI - Learning to recognize younger faces at an older age. AB - OBJECTIVES: Processing of horizontal face cues has been shown to be an important element in face recognition of adults aged up to 30 years. In contrast, horizontally aligned facial features do not appear to contribute to older adults' (60-75 years) recognition in a similar way. To this end, we investigated potential learning effects on the ability to recognize faces based on horizontal features. Previous research suggests face recognition based on all face information experiences an accelerated decline after the age of 70. However, recognition based only on horizontal face information has not yet been studied in old age (75+ years of age). Thus, we investigated whether older adults (aged up to as well as starting at 75 years) can learn to recognize faces based on horizontal face cues alone. METHOD: One younger and two older adult groups (20 30, 60-75, and 75+ years) were familiarized with a high and a low amount of previously unfamiliar faces-some containing all face cues and others containing only horizontal face cues (reduced information). Subsequently, all groups received a recognition test. RESULTS: Repeated learning increased natural face recognition for all three age groups when all face cues were available. However, increases in face recognition were only observed for younger adults when horizontal face cued were only available. DISCUSSION: The importance of horizontally aligned spatial frequencies for recognizing human faces is lessened before the age of 60 (and plateaus thereon), whereas recognition of stimuli containing all face cues is still capable of improvement. PMID- 26850264 TI - A prospective randomized controlled study comparing the pain relief in patients with osteoporotic vertebral compression fractures with the use of vertebroplasty or facet blocking. AB - PURPOSE: To compare the clinical and radiological outcomes of patients undergoing percutaneous vertebroplasty (PVP) versus those undergoing facet blocking (FB) for severe pain due to osteoporotic vertebral compression fractures (OVCFs). METHODS: Two hundred and six patients who had OVCFs on spine radiography and intractable back pain for <=8 weeks were recruited between January 2009 and January 2013 (165 females and 41 males, age >=55 years). Patients were randomly assigned to the PVP group (100 patients) or the FB group (106 patients). VAS, ODI, Roland Morris disability (RMD) scores, scores on the Standardized Physical Component of the SF 36 form (SPC) and scores on the Standardized Mental Component of the SF-36 form (SMC) were determined preoperatively and at each follow-up time (1 day, 1 week, 1, 3, 6, and 12 months). In addition, plain radiographs were obtained at 3, 6, and 12 months postoperatively to detect new fractures. RESULTS: Significantly lower VAS, ODI, and RMD scores for patients in the PVP group compared to those in the FB group were observed at follow-up of 1 day and 1 week (p < 0.05). However, differences in the VAS, ODI, RMD and SPC/MCS (SF-36) scores between the two groups at follow-ups of more than 1 month were statistically insignificant (p > 0.05). Difference in numbers of new fractures in the two groups at the follow-up of 12 months was also statistically insignificant. CONCLUSIONS: PVP produced better pain relief than FB in the short term (<=1 week). However, the difference in pain-relief between these two techniques was insignificant in the long term (follow-up between 1 month and 12 months). PMID- 26850266 TI - Self-monitoring for atrial fibrillation recurrence in the discharge period post cardiac surgery using an iPhone electrocardiogram. AB - OBJECTIVES: Postoperative atrial fibrillation (POAF) occurs in 25-40% of patients following cardiac surgery, and is associated with a significant increased risk of stroke and mortality. Routine surveillance is not performed post-discharge; however, recurrence of POAF can occur in up to 30% of patients discharged in sinus rhythm. This study aimed to determine the feasibility of patients self monitoring with an iPhone handheld electrocardiogram (iECG) to identify recurrence of POAF in the post-discharge period following cardiac surgery. METHODS: Patients with POAF following cardiac surgery were eligible for participation if they had no prior history of atrial fibrillation (AF) and were discharged home in stable sinus rhythm. Participants were provided with an iECG and asked to record a 30-s iECG, four times per day for 4 weeks post-discharge. iECGs were automatically transmitted to a secure server, and reviewed for the presence of AF by the research team and a validated algorithm. All participants also received brief education on AF. RESULTS: Forty-two participants completed the intervention (mean age 69 +/- 9 years, 80% male). Self-monitoring for POAF recurrence using an iECG was feasible and acceptable, and participants felt empowered. Self-monitoring identified 24% (95% confidence interval, 12-39%) with an AF recurrence within 17 days of hospital discharge. These participants were significantly younger than those without AF recurrence (64 +/- 7 vs 70 +/- 10 years; P = 0.025), and had a significantly lower CHA2DS2-VASc score (2.3 +/- 1.2 vs 3.7 +/- 2.3; P = 0.007). However, 80% were at high enough stroke risk to warrant consideration of anticoagulation, i.e. CHA2DS2-VASc score >=2. Only 30% of recurrences were associated with palpitations. Participation also improved AF knowledge from 6.4 +/- 1.8 to 7.3 +/- 1.8 (P = 0.02), of a total score of 10. CONCLUSIONS: Providing patients with an iECG is a non-invasive, inexpensive, convenient and feasible way to monitor for AF recurrence in post-cardiac surgery patients. It also provides a mechanism to provide knowledge about the condition and also potentially reduce anxiety. The success of patients using this technology also has implications for extending the use of iECG self-monitoring to other patient groups such as those undergoing antiarrhythmic interventions for AF. PMID- 26850265 TI - Effect of a randomized controlled exercise trial on bone outcomes: influence of adjuvant endocrine therapy. AB - Bone loss is a significant clinical problem for female cancer survivors (FCS) and increases fracture risk. The aim of the Yale Fitness Intervention Trial (Yale FIT) was to determine the effects of a 12-month aerobic-resistance exercise intervention compared to a home-based physical activity group on bone outcomes [bone mineral density (BMD)] and biomarkers bone turnover). Early postmenopausal FCS (N = 154) were randomized to the exercise intervention (3 times/week) or to a home-based physical activity group. Calcium (1200 mg) and Vitamin D (400 IU) supplements were provided to both groups. BMD was measured at baseline and 12 months. No significant difference in BMD was observed for the exercise vs home based group. However, subjects on Tamoxifen or no endocrine therapy did not significantly lose BMD, with the exception of the femoral neck (FN). In contrast subjects on aromatase inhibitors (AIs) had significant BMD loss at all sites. The majority of subjects had sufficient serum levels of Vitamin D (>20 ng/mL) but there was significantly less bone loss in subjects in the 20-29 ng/mL range at the LS (p = 0.01), hip (p = 0.03), and GT (p = 0.008) compared to lower or higher levels. Exercise stimulates bone remodeling but the intervention was not superior for BMD outcomes at one year. The dose of the osteogenic stimulus in the intervention has been effective in preserving BMD in healthy postmenopausal women but it may be inadequate for survivors with chemotherapy-induced menopause and for those on adjuvant AI therapy. PMID- 26850267 TI - Thoracic endovascular aortic repair for degenerative distal arch aneurysm can be used as a standard procedure in high-risk patients. AB - OBJECTIVES: In recent years, supra-aortic rerouting and thoracic endovascular aortic repair (TEVAR) for treating aortic arch pathology have emerged as a less invasive option for high-risk patients. This study aimed to assess our strategy for preventing stroke and improving late outcomes after supra-aortic rerouting and TEVAR. METHODS: Between July 2008 and July 2015, we performed 280 cases of TEVAR for arch pathologies, using manufactured stent grafts. This study reviewed 101 patients who underwent supra-aortic rerouting and TEVAR for degenerative distal arch aneurysms (80 men, mean age 73.1 years, Zone 1/Zone 2 = 48/53). Since 2011, we have routinely used the brain protection method, which comprises blocking native forward flow from the left common carotid artery (LCA) and left subclavian artery (LSA) for zone 1 cases and the LSA for zone 2 cases before TEVAR. RESULTS: The mean operation time was 178 +/- 65 min. The stroke and 30-day death rates were 3 and 1%, respectively. Before the brain protection method was introduced, the perioperative risk factor for stroke was atheroma Grade >=III (P = 0.035). Proximal landing zone (P = 0.58) and LSA sacrifice (P = 1.00) were not risk factors for stroke. No strokes occurred after using the brain protection method (before protection: 6% and after protection: 0%). Regarding late results, the rate of freedom from aorta-related death at 1 and 4 years was 97 and 95%, respectively. The rate of freedom from aortic events at 1 and 4 years was 91 and 86%, respectively. During follow-up, no type Ia endoleak developed and one type A dissection was observed. CONCLUSIONS: Our strategy for supra-aortic rerouting and TEVAR showed satisfactory early and late results. The chief risk factor for perioperative stroke was atheroma, and blocking native forward flow from the LCA and the LSA prior to the TEVAR procedure helped prevent stroke. PMID- 26850268 TI - Spatial variability of the effect of air pollution on term birth weight: evaluating influential factors using Bayesian hierarchical models. AB - BACKGROUND: Epidemiological studies suggest that air pollution is adversely associated with pregnancy outcomes. Such associations may be modified by spatially-varying factors including socio-demographic characteristics, land-use patterns and unaccounted exposures. Yet, few studies have systematically investigated the impact of these factors on spatial variability of the air pollution's effects. This study aimed to examine spatial variability of the effects of air pollution on term birth weight across Census tracts and the influence of tract-level factors on such variability. METHODS: We obtained over 900,000 birth records from 2001 to 2008 in Los Angeles County, California, USA. Air pollution exposure was modeled at individual level for nitrogen dioxide (NO2) and nitrogen oxides (NOx) using spatiotemporal models. Two-stage Bayesian hierarchical non-linear models were developed to (1) quantify the associations between air pollution exposure and term birth weight within each tract; and (2) examine the socio-demographic, land-use, and exposure-related factors contributing to the between-tract variability of the associations between air pollution and term birth weight. RESULTS: Higher air pollution exposure was associated with lower term birth weight (average posterior effects: -14.7 (95 % CI: -19.8, -9.7) g per 10 ppb increment in NO2 and -6.9 (95 % CI: -12.9, -0.9) g per 10 ppb increment in NOx). The variation of the association across Census tracts was significantly influenced by the tract-level socio-demographic, exposure-related and land-use factors. Our models captured the complex non-linear relationship between these factors and the associations between air pollution and term birth weight: we observed the thresholds from which the influence of the tract-level factors was markedly exacerbated or attenuated. Exacerbating factors might reflect additional exposure to environmental insults or lower socio economic status with higher vulnerability, whereas attenuating factors might indicate reduced exposure or higher socioeconomic status with lower vulnerability. CONCLUSIONS: Our Bayesian models effectively combined a priori knowledge with training data to infer the posterior association of air pollution with term birth weight and to evaluate the influence of the tract-level factors on spatial variability of such association. This study contributes new findings about non-linear influences of socio-demographic factors, land-use patterns, and unaccounted exposures on spatial variability of the effects of air pollution. PMID- 26850271 TI - Cyst aspiration or GnRH antagonist administration for ovarian cysts detected at the start of fresh in vitro fertilization cycles. AB - The primary objective of this study is to investigate the effect of transvaginal ultrasonogram (TVUS)-guided cyst aspiration or gonadotropin releasing hormone antagonist (GnRH-ant) administration for the management of solitary ovarian cysts detected at the start of in vitro fertilization (IVF) cycles on the outcomes of the same cycles. This is a single-center, retrospective, cohort study of patients who had TVUS-guided cyst aspiration or GnRH-ant treatment for ovarian cysts detected at the start of IVF during a 5-year period. Four hundred and three patients met inclusion criteria: 41 (10.2%) underwent cyst aspiration and 362 (89.2%) were treated with GnRH-ant. There was no difference in the demographics or baseline IVF cycle characteristics of the two groups. Patients treated with GnRH-ant had a longer duration of ovarian stimulation (10.8 +/- 3.45 days versus 9.05 +/- 4.06 days, p = 0.003) and required higher gonadotropin doses (3887.7 +/- 1097.8 IU versus 3293.7 +/- 990.5 IU; p = 0.01) compared with the cyst aspiration group. There was no difference in the clinical pregnancy (43.9% versus 41.4%), spontaneous miscarriage (9.76% versus 8.01%) and live birth (34.1% versus 33.4%) rates between the groups. Our findings suggest that cyst aspiration is comparable to GnRH-ant administration for the management of solitary ovarian cysts detected at the start of IVF cycles. PMID- 26850269 TI - Dietary and lifestyle determinants of acrylamide and glycidamide hemoglobin adducts in non-smoking postmenopausal women from the EPIC cohort. AB - PURPOSE: Acrylamide was classified as 'probably carcinogenic' to humans in 1994 by the International Agency for Research on Cancer. In 2002, public health concern increased when acrylamide was identified in starchy, plant-based foods, processed at high temperatures. The purpose of this study was to identify which food groups and lifestyle variables were determinants of hemoglobin adduct concentrations of acrylamide (HbAA) and glycidamide (HbGA) in 801 non-smoking postmenopausal women from eight countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Biomarkers of internal exposure were measured in red blood cells (collected at baseline) by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) . In this cross-sectional analysis, four dependent variables were evaluated: HbAA, HbGA, sum of total adducts (HbAA + HbGA), and their ratio (HbGA/HbAA). Simple and multiple regression analyses were used to identify determinants of the four outcome variables. All dependent variables (except HbGA/HbAA) and all independent variables were log-transformed (log2) to improve normality. Median (25th-75th percentile) HbAA and HbGA adduct levels were 41.3 (32.8-53.1) pmol/g Hb and 34.2 (25.4-46.9) pmol/g Hb, respectively. RESULTS: The main food group determinants of HbAA, HbGA, and HbAA + HbGA were biscuits, crackers, and dry cakes. Alcohol intake and body mass index were identified as the principal determinants of HbGA/HbAA. The total percent variation in HbAA, HbGA, HbAA + HbGA, and HbGA/HbAA explained in this study was 30, 26, 29, and 13 %, respectively. CONCLUSIONS: Dietary and lifestyle factors explain a moderate proportion of acrylamide adduct variation in non-smoking postmenopausal women from the EPIC cohort. PMID- 26850272 TI - Statins and intracerebral hemorrhage: Still missing a mechanism? PMID- 26850273 TI - Auxin-Independent NAC Pathway Acts in Response to Explant-Specific Wounding and Promotes Root Tip Emergence during de Novo Root Organogenesis in Arabidopsis. AB - Plants have powerful regenerative abilities that allow them to recover from damage and survive in nature. De novo organogenesis is one type of plant regeneration in which adventitious roots and shoots are produced from wounded and detached organs. By studying de novo root organogenesis using leaf explants of Arabidopsis (Arabidopsis thaliana), we previously suggested that wounding is the first event that provides signals to trigger the whole regenerative process. However, our knowledge of the role of wounding in regeneration remains limited. In this study, we show that wounding not only triggers the auxin-mediated fate transition of regeneration-competent cells, but also induces the NAC pathway for root tip emergence. The NAC1 transcription factor gene was specifically expressed in response to wounding in the leaf explant, but not in the wounded leaf residue of the source plant. Inhibition of the NAC1 pathway severely affected the emergence of adventitious root tips. However, the NAC1 pathway functioned independently of auxin-mediated cell fate transition and regulates expression of CEP genes, which encode proteins that might have a role in degradation of extensin proteins in the cell wall. Overall, our results suggest that wounding has multiple roles in de novo root organogenesis and that NAC1 acts as one downstream branch in regulating the cellular environment for organ emergence. PMID- 26850270 TI - Divergent adherence estimates with pharmacokinetic and behavioural measures in the MTN-003 (VOICE) study. AB - INTRODUCTION: In the Microbicide Trial Network MTN-003 (VOICE) study, a Phase IIB pre-exposure prophylaxis trial of daily oral or vaginal tenofovir (TFV), product adherence was poor based on pharmacokinetic (PK) drug detection in a random subsample. Here, we sought to compare behavioural and PK measures of adherence and examined correlates of adherence misreporting. METHODS: We included participants with PK and behavioural data from VOICE random subsample. Behavioural assessments included face-to-face interviews (FTFI), audio computer assisted self-interviewing (ACASI) and pharmacy-returned product counts (PC). TFV concentrations < 0.31 ng/mL in plasma (oral group) and < 8.5 ng/swab in vaginal group were defined as "PK non-adherent." Logistic regression models were fit to calculate the combined predictive ability of the behavioural measures as summarized by area under the curve (AUC). Baseline characteristics associated with over-reporting daily product use relative to PK measures was assessed using a Generalized Linear Mixed Model. RESULTS: In this random adherence cohort of VOICE participants assigned to active products, (N = 472), PK non-adherence was 69% in the oral group (N = 314) and 65% in the vaginal group (N = 158). Behaviourally, <= 10% of the cohort reported low/none use with any behavioural measure and accuracy was low (<= 43%). None of the regression models had an AUC > 0.65 for any single or combined behavioural measures. Significant (p < 0.05) correlates of over-reporting included being very worried about getting HIV and being unmarried for the oral group; whereas for the vaginal group, being somewhat worried about HIV was associated with lower risk of over-reporting. CONCLUSIONS: PK measures indicated similarly low adherence for the oral and vaginal groups. No behavioural measure accurately predicted PK non-adherence. Accurate real-time measures to monitor product adherence are urgently needed. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00705679. PMID- 26850275 TI - Salt Stress and Ethylene Antagonistically Regulate Nucleocytoplasmic Partitioning of COP1 to Control Seed Germination. AB - Seed germination, a critical stage initiating the life cycle of a plant, is severely affected by salt stress. However, the underlying mechanism of salt inhibition of seed germination (SSG) is unclear. Here, we report that the Arabidopsis (Arabidopsis thaliana) CONSTITUTIVE PHOTOMORPHOGENESIS1 (COP1) counteracts SSG Genetic assays provide evidence that SSG in loss of function of the COP1 mutant was stronger than this in the wild type. A GUS-COP1 fusion was constitutively localized to the nucleus in radicle cells. Salt treatment caused COP1 to be retained in the cytosol, but the addition of ethylene precursor 1 aminocyclopropane-1-carboxylate had the reverse effect on the translocation of COP1 to the nucleus, revealing that ethylene and salt exert opposite regulatory effects on the localization of COP1 in germinating seeds. However, loss of function of the ETHYLENE INSENSITIVE3 (EIN3) mutant impaired the ethylene mediated rescue of the salt restriction of COP1 to the nucleus. Further research showed that the interaction between COP1 and LONG HYPOCOTYL5 (HY5) had a role in SSG Correspondingly, SSG in loss of function of HY5 was suppressed. Biochemical detection showed that salt promoted the stabilization of HY5, whereas ethylene restricted its accumulation. Furthermore, salt treatment stimulated and ethylene suppressed transcription of ABA INSENSITIVE5 (ABI5), which was directly transcriptionally regulated by HY5. Together, our results reveal that salt stress and ethylene antagonistically regulate nucleocytoplasmic partitioning of COP1, thereby controlling Arabidopsis seed germination via the COP1-mediated down regulation of HY5 and ABI5. These findings enhance our understanding of the stress response and have great potential for application in agricultural production. PMID- 26850274 TI - The Contribution of Carbon and Water in Modulating Wood Formation in Black Spruce Saplings. AB - Nonstructural carbohydrates (NSCs) play a crucial role in xylem formation and represent, with water, the main constraint to plant growth. We assessed the relationships between xylogenesis and NSCs in order to (1) verify the variance explained by NSCs and (2) determine the influence of intrinsic (tissue supplying carbon) and extrinsic (water availability and temperature) factors. During 2 years, wood formation was monitored in saplings of black spruce (Picea mariana) subjected to a dry period of about 1 month in June and exposed to different temperature treatments in a greenhouse. In parallel, NSC concentrations were determined by extracting the sugar compounds from two tissues (cambium and inner xylem), both potentially supplying carbon for wood formation. A mixed-effect model was used to assess and quantify the potential relationships. Total xylem cells, illustrating meristematic activity, were modeled as a function of water, sucrose, and d-pinitol (conditional r(2) of 0.79). Water availability was ranked as the most important factor explaining total xylem cell production, while the contribution of carbon was lower. Cambium stopped dividing under water deficit, probably to limit the number of cells remaining in differentiation without an adequate amount of water. By contrast, carbon factors were ranked as most important in explaining the variation in living cells (conditional r(2) of 0.49), highlighting the functional needs during xylem development, followed by the tissue supplying the NSCs (cambium) and water availability. This study precisely demonstrates the role of carbon and water in structural growth expressed as meristematic activity and tissue formation. PMID- 26850279 TI - Ridding NHS of "unwarranted variation" could save L5bn a year, says report. PMID- 26850276 TI - A Glycosyltransferase from Nicotiana alata Pollen Mediates Synthesis of a Linear (1,5)-alpha-L-Arabinan When Expressed in Arabidopsis. AB - The walls of Nicotiana alata pollen tubes contain a linear arabinan composed of (1,5)-alpha-linked arabinofuranose residues. Although generally found as a side chain on the backbone of the pectic polysaccharide rhamnogalacturonan I, the arabinan in N. alata pollen tubes is considered free, as there is no detectable rhamnogalacturonan I in these walls. Carbohydrate-specific antibodies detected arabinan epitopes at the tip and along the shank of N. alata pollen tubes that are predominantly part of the primary layer of the bilayered wall. A sequence related to ARABINAN DEFICIENT1 (AtARAD1), a presumed arabinan arabinosyltransferase from Arabidopsis (Arabidopsis thaliana), was identified by searching an N alata pollen transcriptome. Transcripts for this ARAD1-like sequence, which we have named N. alata ARABINAN DEFICIENT-LIKE1 (NaARADL1), accumulate in various tissues, most abundantly in the pollen grain and tube, and encode a protein that is a type II membrane protein with its catalytic carboxyl terminus located in the Golgi lumen. The NaARADL1 protein can form homodimers when transiently expressed in Nicotiana benthamiana leaves and heterodimers when coexpressed with AtARAD1 The expression of NaARADL1 in Arabidopsis led to plants with more arabinan in their walls and that also exuded a guttation fluid rich in arabinan. Chemical and enzymatic characterization of the guttation fluid showed that a soluble, linear alpha-(1,5)-arabinan was the most abundant polymer present. These results are consistent with NaARADL1 having an arabinan (1,5) alpha-arabinosyltransferase activity. PMID- 26850277 TI - Modulation of Protein S-Nitrosylation by Isoprene Emission in Poplar. AB - Researchers have been examining the biological function(s) of isoprene in isoprene-emitting (IE) species for two decades. There is overwhelming evidence that leaf-internal isoprene increases the thermotolerance of plants and protects them against oxidative stress, thus mitigating a wide range of abiotic stresses. However, the mechanisms of abiotic stress mitigation by isoprene are still under debate. Here, we assessed the impact of isoprene on the emission of nitric oxide (NO) and the S-nitroso-proteome of IE and non-isoprene-emitting (NE) gray poplar (Populus * canescens) after acute ozone fumigation. The short-term oxidative stress induced a rapid and strong emission of NO in NE compared with IE genotypes. Whereas IE and NE plants exhibited under nonstressful conditions only slight differences in their S-nitrosylation pattern, the in vivo S-nitroso proteome of the NE genotype was more susceptible to ozone-induced changes compared with the IE plants. The results suggest that the nitrosative pressure (NO burst) is higher in NE plants, underlining the proposed molecular dialogue between isoprene and the free radical NO Proteins belonging to the photosynthetic light and dark reactions, the tricarboxylic acid cycle, protein metabolism, and redox regulation exhibited increased S-nitrosylation in NE samples compared with IE plants upon oxidative stress. Because the posttranslational modification of proteins via S-nitrosylation often impacts enzymatic activities, our data suggest that isoprene indirectly regulates the production of reactive oxygen species (ROS) via the control of the S-nitrosylation level of ROS-metabolizing enzymes, thus modulating the extent and velocity at which the ROS and NO signaling molecules are generated within a plant cell. PMID- 26850280 TI - [Infertility and breast cancer: Is there a link? Updated review of the literature and meta-analysis]. AB - The objective of this review was to assess the level of risk of breast cancer of patients consulting for infertility. METHODS: Studies of cohorts and case-control were extracted from the Pubmed database from January 2000 until May 2015 through the following keywords: "infertility"; "endometriosis"; "polycystic ovary syndrome"; "breast cancer", "cancer risk". Eleven publications were finally selected after exclusion of publications dealing with infertility after breast cancer. Our meta-analysis, involving 10 of these publications, was performed using Review Manager software, Cochrane Collaboration, 2014. The results were calculated by etiology of infertility, polycystic ovary syndrome (PCOS) and endometriosis, as well as globally. RESULTS: The analysis of these published epidemiological studies confirms that infertility is not a breast cancer risk factor, but the results are contradictory. Three studies have shown a significantly increased risk of breast cancer in a population of infertile women, while 7 others have not found this risk. These contradictions are due to the heterogeneity of the studies, the included populations, the follow-up periods and confounding factors. Our meta-analysis of the selected studies has not identified a significant association between infertility and breast cancer risk (1.05; 95% CI [0.96-1.16]). A subgroup analysis on endometriosis and PCOS showed no significant association either, with an OR of 1.02 (95% CI [0.87-1.19]) and 1.19 (95% CI [0.93-1.51]), respectively. CONCLUSION: Infertility is not an identified risk factor for breast cancer. A message reassuring about a possible risk of infertility-related breast cancer should be given to these patients. Infertility is therefore not an indication of increased breast surveillance. PMID- 26850281 TI - [Shoulder dystocia: Quality of retranscription in medical files]. AB - OBJECTIVE: Shoulder dystocia is a rare obstetrical event and potentially serious. Apart from possible psychological implications, it may be responsible for maternal (haemorrhage and perineal tear) and neonatal complications (brachial plexus) leading to complaints and even lawsuits. The transcription of this event in medical files is essential as it is a reflection of the work in an emergency. It allows the obstetrician to defend him in case of trial. Our objective was to assess the quality of the transcription of shoulder dystocia situations in medical files. METHOD: Retrospective chart study conducted in a university hospital with maternity type III. The primary objective was the rate of comprehensive records (name maneuvers and order of maneuvers of the anterior shoulder hand, time between the expulsion of the head and body, Apgar score). RESULTS: Between 2007 and 2015, 54 cases of shoulder dystocia requiring a second line maneuver after vaginal delivery (Wood and/or Jacquemier) were included. In all, 98.2% of the files were incomplete. The maneuvers and their order were noted in 100% of cases. However, the operation was not correctly described in 16.7% of cases. The anterior shoulder was noted in 16.7% of cases. The time between the expulsion of the head and the body was noted in one single files. Neither broken collarbone nor brachial plexus were observed. CONCLUSION: To improve the management of dystocia shoulder and transcription of data in files, simulation sessions and the creation of a standardized form would be needed. PMID- 26850282 TI - [Is endometriosis a precancerous lesion? Perspectives and clinical implications]. AB - Epidemiological studies have shown a relationship between endometriosis and clear cell/endometrioid ovarian cancers (named "Endometriosis Associated Ovarian Cancer" or EAOC). The recent discovery of signaling pathways (especially the SWI/SNF and PI3K/AKT/mTOR pathways) that linked endometriosis and EAOC could lead to the development of specific biomarkers as ARID1A to screen benign to premalignant endometriosis and to new targeted treatment. Moreover, the better understanding of the pathogenesis of the epithelial ovarian cancer arising from the Fallopian tube could allow new early prevention strategies that will be described in this review. PMID- 26850278 TI - A Co-Opted Hormonal Cascade Activates Dormant Adventitious Root Primordia upon Flooding in Solanum dulcamara. AB - Soil flooding is a common stress factor affecting plants. To sustain root function in the hypoxic environment, flooding-tolerant plants may form new, aerenchymatous adventitious roots (ARs), originating from preformed, dormant primordia on the stem. We investigated the signaling pathway behind AR primordium reactivation in the dicot species Solanum dulcamara Transcriptome analysis indicated that flooding imposes a state of quiescence on the stem tissue, while increasing cellular activity in the AR primordia. Flooding led to ethylene accumulation in the lower stem region and subsequently to a drop in abscisic acid (ABA) level in both stem and AR primordia tissue. Whereas ABA treatment prevented activation of AR primordia by flooding, inhibition of ABA synthesis was sufficient to activate them in absence of flooding. Together, this reveals that there is a highly tissue-specific response to reduced ABA levels. The central role for ABA in the response differentiates the pathway identified here from the AR emergence pathway known from rice (Oryza sativa). Flooding and ethylene treatment also induced expression of the polar auxin transporter PIN2, and silencing of this gene or chemical inhibition of auxin transport inhibited primordium activation, even though ABA levels were reduced. Auxin treatment, however, was not sufficient for AR emergence, indicating that the auxin pathway acts in parallel with the requirement for ABA reduction. In conclusion, adaptation of S. dulcamara to wet habitats involved co-option of a hormonal signaling cascade well known to regulate shoot growth responses, to direct a root developmental program upon soil flooding. PMID- 26850283 TI - Bioimaging for quantitative phenotype analysis. AB - With the development of bio-imaging techniques, an increasing number of studies apply these techniques to generate a myriad of image data. Its applications range from quantification of cellular, tissue, organismal and behavioral phenotypes of model organisms, to human facial phenotypes. The bio-imaging approaches to automatically detect, quantify, and profile phenotypic changes related to specific biological questions open new doors to studying phenotype-genotype associations and to precisely evaluating molecular changes associated with quantitative phenotypes. Here, we review major applications of bioimage-based quantitative phenotype analysis. Specifically, we describe the biological questions and experimental needs addressable by these analyses, computational techniques and tools that are available in these contexts, and the new perspectives on phenotype-genotype association uncovered by such analyses. PMID- 26850284 TI - Multi-omics data driven analysis establishes reference codon biases for synthetic gene design in microbial and mammalian cells. AB - In this study, we analyzed multi-omics data and subsets thereof to establish reference codon usage biases for codon optimization in synthetic gene design. Specifically, publicly available genomic, transcriptomic, proteomic and translatomic data for microbial and mammalian expression hosts, Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris and Chinese hamster ovary (CHO) cells, were compiled to derive their individual codon and codon pair frequencies. Then, host dependent and -omics specific codon biases were generated and compared by principal component analysis and hierarchical clustering. Interestingly, our results indicated the similar codon bias patterns of the highly expressed transcripts, highly abundant proteins, and efficiently translated mRNA in microbial cells, despite the general lack of correlation between mRNA and protein expression levels. However, for CHO cells, the codon bias patterns among various omics subsets are not distinguishable, forming one cluster. Thus, we further investigated the effect of different input codon biases on codon optimized sequences using the codon context (CC) and individual codon usage (ICU) design parameters, via in silico case study on the expression of human IFNgamma sequence in CHO cells. The results supported that CC is more robust design parameter than ICU for improved heterologous gene design. PMID- 26850285 TI - [Cutaneous consequences of environmental changes]. AB - The skin is normally well protected against a majority of substances. Ultraviolet rays play an essential role in the occurrence of cancer and skin aging. There are numerous pollutants, which act on the skin or enter the body through the skin. The new lifestyle entails new risks. We must be vigilant but also avoid unjustified peremptory opinions scientifically unproven. PMID- 26850286 TI - [Not Available]. PMID- 26850287 TI - A global economic model to assess the cost-effectiveness of new treatments for advanced breast cancer in Canada. AB - Objective Considering the increasing number of treatment options for metastatic breast cancer (MBC), it is important to develop high-quality methods to assess the cost-effectiveness of new anti-cancer drugs. This study aims to develop a global economic model that could be used as a benchmark for the economic evaluation of new therapies for MBC. Methods The Global Pharmacoeconomics of Metastatic Breast Cancer (GPMBC) model is a Markov model that was constructed to estimate the incremental cost per quality-adjusted life years (QALY) of new treatments for MBC from a Canadian healthcare system perspective over a lifetime horizon. Specific parameters included in the model are cost of drug treatment, survival outcomes, and incidence of treatment-related adverse events (AEs). Global parameters are patient characteristics, health states utilities, disutilities, and costs associated with treatment-related AEs, as well as costs associated with drug administration, medical follow-up, and end-of-life care. The GPMBC model was tested and validated in a specific context, by assessing the cost effectiveness of lapatinib plus letrozole compared with other widely used first line therapies for post-menopausal women with hormone receptor-positive (HR+) and epidermal growth factor receptor 2-positive (HER2+) MBC. Results When tested, the GPMBC model led to incremental cost-utility ratios of CA$131 811 per QALY, CA$56 211 per QALY, and CA$102 477 per QALY for the comparison of lapatinib plus letrozole vs letrozole alone, trastuzumab plus anastrozole, and anastrozole alone, respectively. Results of the model testing were quite similar to those obtained by Delea et al., who also assessed the cost-effectiveness of lapatinib in combination with letrozole in HR+/HER2 + MBC in Canada, thus suggesting that the GPMBC model can replicate results of well-conducted economic evaluations. Conclusions The GPMBC model can be very valuable as it allows a quick and valid assessment of the cost-effectiveness of any new treatments for MBC in a Canadian context. PMID- 26850289 TI - Positive and negative gestational handling influences placental traits and mother offspring behavior in dairy goats. AB - Dairy animals are subjected to a number of potential stressors throughout their lives, including daily interactions with humans. The quality of these interactions may have direct consequences for the animal undergoing the experience, but if such events occur during gestation it may also affect the developing fetus. This study examined the effects of differential handling during mid-gestation in 40 twin-bearing Saanen*Toggenburg primiparous goats. Between days 80 and 115 of gestation (gestation=150 days), goats were subjected to aversive (AVS, n=13), gentle (GEN, n=13) or minimal (M, n=14) handling protocols for 10 minute periods twice daily. The control (M) group did not receive handling treatments and all goats received normal husbandry procedures outside treatment periods. Salivary cortisol measured during the treatment period was higher in AVS goats (mean cortisol (sem) in pg/MUl: AVS: 176.7 (18.2), GEN: 119.6 (11.1), M: 126.5 (13.7); P=0.007). Data collection was focussed on mother-offspring behaviors 2h post-partum, placental morphology and colostrum quality. AVS goats were the only treatment group to suffer fetal loss (16% loss vs 0% in GEN and M, P=0.05). Treatment also influenced placental morphology with a tendency for fewer cotyledons evident in placentae from the aversive treatment (AVS: 87.9 (7.8), GEN: 107.1 (7.9), M: 112.1 (9.3), P=0.093), and significantly fewer medium sized cotyledons (AVS: 67.6 (7.8), GEN: 89.3 (6.4), M: 84.3 (5.4), P=0.042). GEN goats displayed more grooming and nosing behaviors towards their young during the first 2h post-partum (grooming: GEN: 89.3% (7.1), AVS: 72.6% (7.7), M: 63.4% (9.0), P=0.045; nosing frequency: GEN: 58.8 (12.5), AVS: 28.6 (11.1), M: 34.7 (6.5), P=0.021). There was an overall trend for kids from mothers experiencing the AVS treatment to take longer to stand, reach the udder and suck compared to kids from GEN and M treatment groups. Treatment significantly affected latency to perform play behavior, with kids from AVS goats taking on average 25 min longer to play for the first time than kids from GEN and M treatment groups (P<0.001). The results show that handling during gestation affects placental morphology, fetal survival and post-partum maternal behaviors, and influences kid behavioral development. Such results have important animal welfare implications, demonstrating that negative handling of pregnant females results in poorer placental quality with potential for fetal loss. It also demonstrates the beneficial effects of positive handling on enhancement of maternal behaviors. PMID- 26850290 TI - Diet-induced obesity resistance of adult female mice selectively bred for increased wheel-running behavior is reversed by single perinatal exposure to a high-energy diet. AB - Female mice from independently bred lines previously selected over 50 generations for increased voluntary wheel-running behavior (S1, S2) resist high energy (HE) diet-induced obesity (DIO) at adulthood, even without actual access to running wheels, as opposed to randomly bred controls (CON). We investigated whether adult S mice without wheels remain DIO-resistant when exposed - via the mother - to the HE diet during their perinatal stage (from 2 weeks prior to conception until weaning on post-natal day 21). While S1 and S2 females subjected to HE diet either perinatally or from weaning onwards (post-weaning) resisted increased adiposity at adulthood (as opposed to CON females), they lost this resistance when challenged with HE diet during these periods combined over one single cycle of breeding. When allowed one-week access to wheels (at week 6-8 and at 10 months), however, tendency for increased wheel-running behavior of S mice was unaltered. Thus, the trait for increased wheel-running behavior remained intact following combined perinatal and post-weaning HE exposure, but apparently this did not block HE-induced weight gain. At weaning, perinatal HE diet increased adiposity in all lines, but this was only associated with hyperleptinemia in S lines irrespective of gender. Because leptin has multiple developmental effects at adolescence, we argue that a trait for increased physical activity may advance maturation in times of plenty. This would be adaptive in nature where episodes of increased nutrient availability should be exploited maximally. Associated disturbances in glucose homeostasis and related co-morbidities at adulthood are probably pleiotropic side effects. PMID- 26850291 TI - Behavioural and physiological measures indicate subtle variations in the emotional valence of young pigs. AB - In the study of animal emotions, emotional valence has been found to be difficult to measure. Many studies of farm animals' emotions have therefore focussed on the identification of indicators of strong, mainly negative, emotions. However, subtle variations in emotional valence, such as those caused by rather moderate differences in husbandry conditions, may also affect animals' mood and welfare when such variations occur consistently. In this study, we investigated whether repeated moderate aversive or rewarding events could lead to measurable differences in emotional valence in young, weaned pigs. We conditioned 105 female pigs in a test arena to either a repeated startling procedure (sudden noises or appearances of objects) or a repeated rewarding procedure (applesauce, toy and straw) over 11 sessions. Control pigs were also regularly exposed to the same test arena but without conditioning. Before and after conditioning, we measured heart rate and its variability as well as the behavioural reactions of the subjects in the test arena, with a special focus on detailed acoustic analyses of their vocalisations. The behavioural and heart rate measures were analysed as changes compared to the baseline values before conditioning. A limited number of the putative indicators of emotional valence were affected by the conditioning. We found that the negatively conditioned pigs showed changes that were significantly different from those in control pigs, namely a decrease in locomotion and an increase in standing. The positively conditioned pigs, however, showed a stronger increase in heart rate and a smaller decrease in SDNN (a heart rate variability parameter indicating changes in autonomic regulation) compared to the controls. Compared to the negatively conditioned pigs, the positively conditioned pigs produced fewer vocalisations overall as well as fewer low frequency grunts but more high-frequency grunts. The low-frequency grunts of the negatively conditioned pigs also showed lower frequency parameters (bandwidth, maximum frequency, 25% and 50% quartiles) compared to those of the positively conditioned pigs. In any of the statistically significant results, the conditioning accounted for 1.5-11.9% of variability in the outcome variable. Hence, we conclude that repeated moderate aversive and rewarding events have weak but measurable effects on some aspects of behaviour and physiology in young pigs, possibly indicating changes in emotional valence, which could ultimately affect their welfare. The combination of ethophysiological indicators, i.e., the concurrent examination of heart rate measures, behavioural responses and especially vocalisation patterns, as used in the current study, might be a useful way of examining subtle effects on emotional valence in further studies. PMID- 26850292 TI - McCune-Albright syndrome, natural history and multidisciplinary management in a series of 14 pediatric cases. AB - BACKGROUND: McCune-Albright syndrome is a rare disorder characterized by endocrine disorders, cafe-au-lait spots and fibrous dysplasia of bone that occurs early in life. METHODS: A series of 14 pediatric cases were followed between 1994 and 2013 by the competence center for rare endocrine diseases and constitutional bone diseases at CHU de Nancy (France). The diagnosis is based on the presence of at least two symptoms. RESULTS: The mean follow-up was 6 years (1-17 years). The sex ratio was six girls per boy. The incidence was 0.28 cases/million population/year. Mean age at diagnosis was 6 years. A mutation in the GNAS gene was found in 33% of patients tested. Gonadal involvement (13/14 cases), including early peripheral puberty and ovarian cysts in girls (82%) occurred on average at 4 years of age. Bone involvement (10/14 cases) appeared on average at 5 years of age and was most often multiple (80%) with fracture risk, and the skull, with a neurosensory risk. CONCLUSION: Clinical definition and methods of screening and monitoring can be improved to allow for an earlier intervention. It must be multidisciplinary and take into account the disability and quality of life of the patient. PMID- 26850293 TI - Intoxications involving the fentanyl analogs acetylfentanyl, 4 methoxybutyrfentanyl and furanylfentanyl: results from the Swedish STRIDA project. AB - BACKGROUND: Potent and potentially harmful new psychoactive substances (NPS) are continuously introduced on the recreational drugs market. This report from the Swedish STRIDA project describes analytically confirmed cases of intoxication involving the fentanyl analogs acetylfentanyl, 4-methoxybutyrfentanyl, and furanylfentanyl. METHODS: Patients with suspected NPS exposure presenting in emergency departments and intensive care units in Sweden and requiring hospital care are invited to the STRIDA project. Toxicological analysis of serum and urine samples was performed by multi-component liquid chromatographic-mass spectrometric methods. Data on clinical features were retrieved from telephone consultations with the Swedish Poisons Information Centre and from medical records. RESULTS: Between April and November 2015, 14 analytically confirmed intoxications involving acetylfentanyl (nine cases), 4-methoxybutyrfentanyl (3), furanylfentanyl (1), and 4-methoxybutyrfentanyl together with furanylfentanyl (1) were identified. The patients were aged 20-40 (mean 28.5) years and 86% were men. Twelve patients (86%) were admitted to intensive care, where two required intubation and mechanical ventilation. Typical clinical features were decreased consciousness, respiratory depression, and miosis. In eight cases, the antidote naloxone was administered to counter the effects. The serum acetylfentanyl concentration (N = 7) was 0.6-51.6 (mean 18.3 and median 14.8) ng/mL, and in urine (N = 8) 0.1-686 (mean 155 and median 66.6) ng/mmol creatinine. The serum 4 methoxybutyrfentanyl concentration (N = 2) was 1.3 and 3.1 ng/mL, and 5.1-51.3 ng/mmol creatinine in urine (N = 3). For furanylfentanyl, the serum concentrations were 4.4 and 148 ng/mL and in urine 9.2 and 85 ng/mmol creatinine, respectively. In 13 cases (93%), other NPS and/or classical drugs were also detected. Drug products brought to hospital by patients contained acetylfentanyl (nasal spray and pink tablet), 4-methoxybutyrfentanyl (green tablet), furanylfentanyl/traces of 4-methoxybutyrfentanyl (nasal spray), and 4 fluorobutyrfentanyl (purple tablet). CONCLUSION: Potentially life-threatening opioid toxicity was seen in acute intoxications involving acetylfentanyl, 4 methoxybutyrfentanyl, and furanylfentanyl. Intensive care treatment for one month was necessary in one acetylfentanyl case and one acetylfentanyl patient died from cerebral hemorrhage. PMID- 26850294 TI - High-Throughput Single-Cell Cultivation on Microfluidic Streak Plates. AB - This paper describes the microfluidic streak plate (MSP), a facile method for high-throughput microbial cell separation and cultivation in nanoliter sessile droplets. The MSP method builds upon the conventional streak plate technique by using microfluidic devices to generate nanoliter droplets that can be streaked manually or robotically onto petri dishes prefilled with carrier oil for cultivation of single cells. In addition, chemical gradients could be encoded in the droplet array for comprehensive dose-response analysis. The MSP method was validated by using single-cell isolation of Escherichia coli and antimicrobial susceptibility testing of Pseudomonas aeruginosa PAO1. The robustness of the MSP work flow was demonstrated by cultivating a soil community that degrades polycyclic aromatic hydrocarbons. Cultivation in droplets enabled detection of the richest species diversity with better coverage of rare species. Moreover, isolation and cultivation of bacterial strains by MSP led to the discovery of several species with high degradation efficiency, including four Mycobacterium isolates and a previously unknown fluoranthene-degrading Blastococcus species. PMID- 26850295 TI - New Recombinant Mycobacterium bovis BCG Expression Vectors: Improving Genetic Control over Mycobacterial Promoters. AB - The expression of many antigens, stimulatory molecules, or even metabolic pathways in mycobacteria such as Mycobacterium bovis BCG or M. smegmatis was made possible through the development of shuttle vectors, and several recombinant vaccines have been constructed. However, gene expression in any of these systems relied mostly on the selection of natural promoters expected to provide the required level of expression by trial and error. To establish a systematic selection of promoters with a range of strengths, we generated a library of mutagenized promoters through error-prone PCR of the strong PL5 promoter, originally from mycobacteriophage L5. These promoters were cloned upstream of the enhanced green fluorescent protein reporter gene, and recombinant M. smegmatis bacteria exhibiting a wide range of fluorescence levels were identified. A set of promoters was selected and identified as having high (pJK-F8), intermediate (pJK B7, pJK-E6, pJK-D6), or low (pJK-C1) promoter strengths in both M. smegmatis and M. bovisBCG. The sequencing of the promoter region demonstrated that it was extensively modified (6 to 11%) in all of the plasmids selected. To test the functionality of the system, two different expression vectors were demonstrated to allow corresponding expression levels of the Schistosoma mansoni antigen Sm29 in BCG. The approach used here can be used to adjust expression levels for synthetic and/or systems biology studies or for vaccine development to maximize the immune response. PMID- 26850296 TI - Ultrastructural Variability of the Exosporium Layer of Clostridium difficile Spores. AB - The anaerobic sporeformer Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea in developed and developing countries. The metabolically dormant spore form is considered the transmission, infectious, and persistent morphotype, and the outermost exosporium layer is likely to play a major role in spore-host interactions during the first contact of C. difficile spores with the host and for spore persistence during recurrent episodes of infection. Although some studies on the biology of the exosporium have been conducted (J. Barra-Carrasco et al., J Bacteriol 195:3863-3875, 2013, http://dx.doi.org/10.1128/JB.00369-13; J. Phetcharaburanin et al., Mol Microbiol 92:1025-1038, 2014, http://dx.doi.org/10.1111/mmi.12611), there is a lack of information on the ultrastructural variability and stability of this layer. In this work, using transmission electron micrographs, we analyzed the variability of the spore's outermost layers in various strains and found distinctive variability in the ultrastructural morphotype of the exosporium within and between strains. Through transmission electron micrographs, we observed that although this layer was stable during spore purification, it was partially lost after 6 months of storage at room temperature. These observations were confirmed by indirect immunofluorescence microscopy, where a significant decrease in the levels of two exosporium markers, the N-terminal domain of BclA1 and CdeC, was observed. It is also noteworthy that the presence of the exosporium marker CdeC on spores obtained from C. difficile biofilms depended on the biofilm culture conditions and the strain used. Collectively, these results provide information on the heterogeneity and stability of the exosporium surface of C. difficile spores. These findings have direct implications and should be considered in the development of novel methods to diagnose and/or remove C. difficile spores by using exosporium proteins as targets. PMID- 26850297 TI - Enhancing the alpha-Cyclodextrin Specificity of Cyclodextrin Glycosyltransferase from Paenibacillus macerans by Mutagenesis Masking Subsite -7. AB - Cyclodextrin glycosyltransferases (CGTases) (EC 2.4.1.19) catalyze the conversion of starch or starch derivates into mixtures of alpha-, beta-, and gamma cyclodextrins. Because time-consuming and expensive purification procedures hinder the widespread application of single-ingredient cyclodextrins, enzymes with enhanced specificity are needed. In this study, we tested the hypothesis that the alpha-cyclodextrin selectivity of Paenibacillus macerans alpha-CGTase could be augmented by masking subsite -7 of the active site, blocking the formation of larger cyclodextrins, particularly beta-cyclodextrin. Five single mutants and three double mutants designed to remove hydrogen-bonding interactions between the enzyme and substrate at subsite -7 were constructed and characterized in detail. Although the rates of alpha-cyclodextrin formation varied only modestly, the rate of beta-cyclodextrin formation decreased dramatically in these mutants. The increase in alpha-cyclodextrin selectivity was directly proportional to the increase in the ratio of their kcat values for alpha- and beta cyclodextrin formation. The R146A/D147P and R146P/D147A double mutants exhibited ratios of alpha-cyclodextrin to total cyclodextrin production of 75.1% and 76.1%, approximately one-fifth greater than that of the wild-type enzyme (63.2%), without loss of thermostability. Thus, these double mutants may be more suitable for the industrial production of alpha-cyclodextrin than the wild-type enzyme. The production of beta-cyclodextrin by these mutants was almost identical to their production of gamma-cyclodextrin, which was unaffected by the mutations in subsite -7, suggesting that subsite -7 was effectively blocked by these mutations. Further increases in alpha-cyclodextrin selectivity will require identification of the mechanism or mechanisms by which these small quantities of larger cyclodextrins are formed. PMID- 26850298 TI - Linking Microbial Community and Catabolic Gene Structures during the Adaptation of Three Contaminated Soils under Continuous Long-Term Pollutant Stress. AB - Three types of contaminated soil from three geographically different areas were subjected to a constant supply of benzene or benzene/toluene/ethylbenzene/xylenes (BTEX) for a period of 3 months. Different from the soil from Brazil (BRA) and Switzerland (SUI), the Czech Republic (CZE) soil which was previously subjected to intensive in situ bioremediation displayed only negligible changes in community structure. BRA and SUI soil samples showed a clear succession of phylotypes. A rapid response to benzene stress was observed, whereas the response to BTEX pollution was significantly slower. After extended incubation, actinobacterial phylotypes increased in relative abundance, indicating their superior fitness to pollution stress. Commonalities but also differences in the phylotypes were observed. Catabolic gene surveys confirmed the enrichment of actinobacteria by identifying the increase of actinobacterial genes involved in the degradation of pollutants. Proteobacterial phylotypes increased in relative abundance in SUI microcosms after short-term stress with benzene, and catabolic gene surveys indicated enriched metabolic routes. Interestingly, CZE soil, despite staying constant in community structure, showed a change in the catabolic gene structure. This indicates that a highly adapted community, which had to adjust its gene pool to meet novel challenges, has been enriched. PMID- 26850299 TI - Biofilm and Planktonic Bacterial and Fungal Communities Transforming High Molecular-Weight Polycyclic Aromatic Hydrocarbons. AB - High-molecular-weight polycyclic aromatic hydrocarbons (HMW-PAHs) are natural components of fossil fuels that are carcinogenic and persistent in the environment, particularly in oil sands process-affected water (OSPW). Their hydrophobicity and tendency to adsorb to organic matter result in low bioavailability and high recalcitrance to degradation. Despite the importance of microbes for environmental remediation, little is known about those involved in HMW-PAH transformations. Here, we investigated the transformation of HMW-PAHs using samples of OSPW and compared the bacterial and fungal community compositions attached to hydrophobic filters and in suspension. It was anticipated that the hydrophobic filters with sorbed HMW-PAHs would select for microbes that specialize in adhesion. Over 33 days, more pyrene was removed (75% +/- 11.7%) than the five-ring PAHs benzo[a]pyrene (44% +/- 13.6%) and benzo[b]fluoranthene (41% +/- 12.6%). For both bacteria and fungi, the addition of PAHs led to a shift in community composition, but thereafter the major factor determining the fungal community composition was whether it was in the planktonic phase or attached to filters. In contrast, the major determinant of the bacterial community composition was the nature of the PAH serving as the carbon source. The main bacteria enriched by HMW-PAHs were Pseudomonas, Bacillus, and Microbacterium species. This report demonstrates that OSPW harbors microbial communities with the capacity to transform HMW-PAHs. Furthermore, the provision of suitable surfaces that encourage PAH sorption and microbial adhesion select for different fungal and bacterial species with the potential for HMW-PAH degradation. PMID- 26850300 TI - CO Metabolism in the Thermophilic Acetogen Thermoanaerobacter kivui. AB - The thermophilic acetogenic bacterium Thermoanaerobacter kivui, previously described not to use carbon monoxide as a carbon and energy source, was adapted to grow on CO. This was achieved by using a preculture grown on H2 plus CO2 and by increasing the CO concentration in small, 10% increments.T. kivui was finally able to grow within a 100% CO atmosphere. Growth on CO was found in complex and mineral media, and vitamins were not required. Carbon monoxide consumption was accompanied by acetate and hydrogen production. Cells also grew on synthesis gas (syngas) with the simultaneous use of CO and H2 coupled to acetate production. CO oxidation in resting cells was coupled to hydrogen and acetate production and accompanied by the synthesis of ATP. A protonophore abolished ATP synthesis but stimulated H2 production, which is consistent with a chemiosmotic mechanism of ATP synthesis. Hydrogenase activity was highest in crude extracts of CO-grown cells, and carbon monoxide dehydrogenase (CODH) activity was highest in H2-plus CO2- or CO-grown cells. The genome of T. kivui harbors two CODH gene clusters, and both CODH proteins were present in crude extracts, but one CODH was more prevalent in crude extracts from CO-grown cells. PMID- 26850301 TI - Global Transcriptional Regulation of Backbone Genes in Broad-Host-Range Plasmid RA3 from the IncU Group Involves Segregation Protein KorB (ParB Family). AB - The KorB protein of the broad-host-range conjugative plasmid RA3 from the IncU group belongs to the ParB family of plasmid and chromosomal segregation proteins. As a partitioning DNA-binding factor, KorB specifically recognizes a 16-bp palindrome which is an essential motif in the centromere-like sequence parSRA3, forms a segrosome, and together with its partner IncC (ParA family) participates in active DNA segregation ensuring stable plasmid maintenance. Here we show that by binding to this palindromic sequence, KorB also acts as a repressor for the adjacent mobC promoter driving expression of the mobC-nicoperon, which is involved in DNA processing during conjugation. Three other promoters, one buried in the conjugative transfer module and two divergent promoters located at the border between the replication and stability regions, are regulated by KorB binding to additional KorB operators (OBs). KorB acts as a repressor at a distance, binding to OBs separated from their cognate promoters by between 46 and 1,317 nucleotides. This repressor activity is facilitated by KorB spreading along DNA, since a polymerization-deficient KorB variant with its dimerization and DNA binding abilities intact is inactive in transcriptional repression. KorB may act as a global regulator of RA3 plasmid functions in Escherichia coli, since its overexpression in transnegatively interferes with mini-RA3 replication and stable maintenance of RA3. PMID- 26850302 TI - Metabolic Engineering of Probiotic Saccharomyces boulardii. AB - Saccharomyces boulardiiis a probiotic yeast that has been used for promoting gut health as well as preventing diarrheal diseases. This yeast not only exhibits beneficial phenotypes for gut health but also can stay longer in the gut than Saccharomyces cerevisiae Therefore, S. boulardiiis an attractive host for metabolic engineering to produce biomolecules of interest in the gut. However, the lack of auxotrophic strains with defined genetic backgrounds has hampered the use of this strain for metabolic engineering. Here, we report the development of well-defined auxotrophic mutants (leu2,ura3,his3, and trp1) through clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-based genome editing. The resulting auxotrophic mutants can be used as a host for introducing various genetic perturbations, such as overexpression or deletion of a target gene, using existing genetic tools forS. cerevisiae We demonstrated the overexpression of a heterologous gene (lacZ), the correct localization of a target protein (red fluorescent protein) into mitochondria by using a protein localization signal, and the introduction of a heterologous metabolic pathway (xylose-assimilating pathway) in the genome ofS. boulardii We further demonstrated that human lysozyme, which is beneficial for human gut health, could be secreted by S. boulardii Our results suggest that more sophisticated genetic perturbations to improveS. boulardii can be performed without using a drug resistance marker, which is a prerequisite for in vivo applications using engineeredS. boulardii. PMID- 26850303 TI - Simultaneous Rapid Detection and Serotyping of Cronobacter sakazakii Serotypes O1, O2, and O3 by Using Specific Monoclonal Antibodies. AB - Cronobacter sakazakii is a foodborne pathogen associated with rare but often lethal infections in neonates. Powdered infant formula (PIF) represents the most frequent source of infection. Out of the identified serotypes (O1 to O7), O1, O2, and O3 are often isolated from clinical and PIF samples. Serotype-specific monoclonal antibodies (MAbs) suitable for application in enzyme immunoassays (EIAs) for the rapid detection of C. sakazakii have not yet been developed. In this study, we created specific MAbs with the ability to bind toC. sakazakii of serotypes O1, O2, and O3. Characterization by indirect EIAs, immunofluorescence, motility assays, and immunoblotting identified lipopolysaccharide (LPS) and exopolysaccharide (EPS) as the antigenic determinants of the MAbs. The established sandwich EIAs were highly sensitive and were able to detect between 2 * 10(3)and 9 * 10(6)CFU/ml. Inclusivity tests confirmed that 93% of serotype O1 strains, 100% of O2 strains, and 87% of O3 strains were detected at low cell counts. No cross-reactivity with >100 strains of Cronobacter spp. and other Enterobacter iaceae was observed, except for that with C. sakazakii serotype O3 and Cronobacter muytjensii serotype O1. Moreover, the sandwich EIAs detected C. sakazakii in PIF samples artificially contaminated with 1 to 10 bacterial cells per 10 g of sample after 15 h of preenrichment. The use of these serotype specific MAbs not only allows the reliable detection of C. sakazakii strains but also enables simultaneous serotyping in a simple sandwich EIA method. PMID- 26850304 TI - Host Plant Determines the Population Size of an Obligate Symbiont (Buchnera aphidicola) in Aphids. AB - Buchnera aphidicolais an obligate endosymbiont that provides aphids with several essential nutrients. Though much is known about aphid-Buchnera interactions, the effect of the host plant on Buchnera population size remains unclear. Here we used quantitative PCR (qPCR) techniques to explore the effects of the host plant on Buchnera densities in the cotton-melon aphid, Aphis gossypii Buchneratiters were significantly higher in populations that had been reared on cucumber for over 10 years than in populations maintained on cotton for a similar length of time. Aphids collected in the wild from hibiscus and zucchini harbored more Buchnera symbionts than those collected from cucumber and cotton. The effect of aphid genotype on the population size of Buchnera depended on the host plant upon which they fed. When aphids from populations maintained on cucumber or cotton were transferred to novel host plants, host survival and Buchnera population size fluctuated markedly for the first two generations before becoming relatively stable in the third and later generations. Host plant extracts from cucumber, pumpkin, zucchini, and cowpea added to artificial diets led to a significant increase in Buchnera titers in the aphids from the population reared on cotton, while plant extracts from cotton and zucchini led to a decrease in Buchnera titers in the aphids reared on cucumber. Gossypol, a secondary metabolite from cotton, suppressed Buchnera populations in populations from both cotton and cucumber, while cucurbitacin from cucurbit plants led to higher densities. Together, the results suggest that host plants influence Buchnera population processes and that this may provide phenotypic plasticity in host plant use for clonal aphids. PMID- 26850305 TI - Coagulopathy in Traumatic Brain Injury and Its Correlation with Progressive Hemorrhagic Injury: A Systematic Review and Meta-Analysis. AB - The association between coagulopathy and either isolated traumatic brain injury (TBI) or progressive hemorrhagic injury (PHI) remains controversial. The aims of this study were to evaluate whether isolated TBI induces pronounced coagulopathy, in comparison with non-TBI or TBI in conjunction with other injuries (TBI + other injuries), and to examine whether there is any evidence of a relationship between coagulopathy and PHI in patients who have experienced TBI. The MEDLINE((r)) and Embase databases, and the Cochrane Central Register of Controlled Trials (Central), were trawled for relevant studies. Searches covered the period from the inception of each of the databases to June 2015, and were conducted using appropriate combinations of terms and key words based on medical subject headings (MeSH). Studies were included if they compared isolated TBI with a similar severity of injury to other body regions, or compared PHI with non-PHI, with regard to coagulation tests and the prevalence of coagulopathy. We extracted the means and standard deviations (SD) of coagulation test levels, as well as their ranges or the percentage of abnormal coagulation tests, in both cases and controls. A total of 19 studies were included in our systematic review and meta analysis. Only the mean fibrinogen (FIB) in isolated TBI was found to be significantly higher than in TBI + other injuries (pooled mean difference [MD] 32.09; 95% confidence interval [CI] 4.92-59.25; p = 0.02); in contrast, it was also significantly higher than in non-TBI (pooled MD 15.44; 95% CI 0.28-30.59; p = 0.05). We identified 15 studies that compared coagulopathy between a PHI group and a non-PHI group. The PHI group had a lower platelet count (PLT) value (pooled MD -19.21; 95% CI: -26.99 to -11.44, p < 0.001) and a higher international normalized ratio (INR) value (pooled MD 0.07; 95% CI: 0.02-0.13, p = 0.006) than the non-PHI group, but no differences were observed in the mean activated partial thromboplastin time (APTT) and prothrombin time (PT) between the PHI and non-PHI patients. In addition, PHI was significantly associated with a higher percentage of INR >1.2 (pooled OR 3.49 [95% CI 1.97-6.20], p < 0.001), PLT <100 * 109/L (pooled OR 4.74 [95% CI 2.44-9.20], p < 0.001), and coagulopathy (pooled OR 2.52; 95% CI 1.88- 3.38; p < 0.001), compared with non-PHI. The current clinical evidence does not indicate that the prevalence of coagulopathy in TBI is significantly higher than in injuries of similar severity to other areas of the body, or in multiple injuries with TBI. With respect to the association between coagulopathy and PHI, the occurrence of coagulopathy, INR, and PLT was significantly associated with PHI, but APTT and PT were not found to be associated with PHI. In the future, high quality research will be required to further characterize the effects of coagulopathy on TBI and subsequent PHI. PMID- 26850307 TI - Comparison of early effects of budesonide/formoterol maintenance and reliever therapy with fluticasone furoate/vilanterol for asthma patients requiring step-up from inhaled corticosteroid monotherapy. AB - BACKGROUND: If asthma patients fail to achieve symptom control using a medium dose of inhaled corticosteroid (ICS) alone, addition of a long-acting beta2 agonist (LABA) is the preferred treatment. Currently, there are several combinations of ICS/LABA that are available, each of which has a different property. Here, we aimed to compare the early effects of budesonide/formoterol (BUD/FM; Symbicort((r))) for maintenance and reliever therapy (SMART) with a fixed dose of fluticasone furoate/vilanterol (FF/VI; Relvar((r))). METHODS: Inadequately controlled asthma patients (defined as having an Asthma Control Questionnaire, 5-item version [ACQ5] score>=1.5) with a fractional exhaled nitric oxide (FeNO) value > 35 ppb, who had been treated with a medium dose of ICS alone, were enrolled. Patients were randomized into two groups and treated with two inhalations twice-daily of BUD/FM 160/4.5 MUg plus as-needed BUD/FM (SMART group, n = 15) or one inhalation once-daily of FF/VI 100/25 MUg plus as-needed procaterol (FF/VI group, n = 15) for 4 weeks. Outcomes including FeNO, impulse oscillometry (IOS) parameters and ACQ5 scores were measured at 0, 2 and 4 weeks. RESULTS: Both groups showed improvement in airway inflammation, pulmonary function and symptoms from baseline to 2 weeks. From 2 to 4 weeks, the SMART group exhibited continuous improvement in most measured parameters, whereas improvement in the FF/VI group seemed to reach a plateau transiently. Consequently, the SMART group showed significant improvement in the FeNO, IOS parameters (resonance frequency and integrated area of low frequency reactance) and ACQ5 score as compared with the FF/VI group at 4 weeks. CONCLUSION: As compared with the FF/VI group, the SMART group achieved a greater improvement in FeNO, small airway parameters regarding IOS and ACQ score, in patients with airway inflammation and uncontrolled symptoms treated with a medium dose of ICS alone. In this 4-week study, these two ICS/LABA combination therapies showed different treatment outcomes; they must be investigated further to clarify suitable patient characters and the long term efficacies for each combination. PMID- 26850306 TI - Alkynyl gold(I) phosphane complexes: Evaluation of structure-activity relationships for the phosphane ligands, effects on key signaling proteins and preliminary in-vivo studies with a nanoformulated complex. AB - Gold alkynyl complexes with phosphane ligands of the type (alkynyl)Au(I)(phosphane) represent a group of bioorganometallics, which has only recently been evaluated biologically in more detail. Structure-activity relationship studies regarding the residues of the phosphane ligand (P(Ph)3, P(2 furyl)3, P(DAPTA)3, P(PTA)3, P(Et)3, P(Me)3) of complexes with an 4 ethynylanisole alkyne ligand revealed no strong differences concerning cytotoxicity. However, a relevant preference for the heteroatom free alkyl/aryl residues concerning inhibition of the target enzyme thioredoxin reductase was evident. Complex 1 with the triphenylphosphane ligand was selected for further studies, in which clear effects on cell morphology were monitored by time-lapse microscopy. Effects on cellular signaling were determined by ELISA microarrays and showed a significant induction of the phosphorylation of ERK1 (extracellular signal related kinase 1), ERK2 and HSP27 (heat shock protein 27) in HT-29 cells. Application of 1 in-vivo in a mouse xenograft model was found to be challenging due to the low solubility of the complex and required a formulation strategy based on a peanut oil nanoemulsion. PMID- 26850308 TI - Francois Jacob, Andre Lwoff and Jacques Monod, fifty years after the Nobel Prize. PMID- 26850309 TI - Structural equation modeling of the associations between the home environment and obesity-related cardiovascular fitness and insulin resistance among Hispanic children. AB - Hispanic children are disproportionally affected by obesity-related risk of metabolic disease. We used the structural equation modeling to examine the associations between specific diet and physical activity (PA) behaviors at home and Hispanic children's metabolic health. A total of 187 Hispanic children and their parents from an urban community in Wisconsin participated in the study. Exposure variables included, children's daily intake of sugar-sweetened beverages (SSB) and PA; home availability of SSB and PA areas/equipment; and parents' intake of SSB and PA, assessed through self-administered questionnaires. Outcome variables for children's metabolic health included, measured anthropometrics; cardiovascular fitness assessed using the Progressive Aerobic Cardiovascular Endurance Run (PACER); and insulin resistance determined with the homeostasis model assessment of insulin resistance (HOMAIR). We found that children's daily intake of SSB was positively associated with BMI z-score, which in turn, was positively associated with HOMAIR (P < 0.05). Specific diet behaviors at home associated with children's intake of SSB, included home availability of SSB, which mediated the association between parents' and children's intake of SSB (P < 0.05). Children's PA was positively associated with PACER z-score, which in turn, was inversely associated with HOMAIR (P < 0.05). Specific PA behaviors at home associated with children's PA, included home availability of PA areas/equipment, which mediated the association between parents' and children's PA (P < 0.05). The structural equation model indices suggested a satisfactory model fit (Chi-square, X(2) = 53.1, comparative fix index = 0.92, root-mean-squared error associated = 0.04). The findings confirm the need for interventions at the family level that promotes healthier home environments by targeting poor diet and low levels of PA in all family members. PMID- 26850310 TI - Nutrition education effective in increasing fruit and vegetable consumption among overweight and obese adults. AB - Despite the benefits of fruit and vegetable consumption on weight and decreased risk for chronic disease, Americans' intake of fruits and vegetables is well below the recommended daily servings. While previous studies have assessed fruit and vegetable consumption and the influence of educational interventions on fruit and vegetable intake, no studies to date have examined the effects of nutrition education combined with provision of fruits and vegetables on changes in fruit and vegetable consumption among overweight and obese adults. The objectives of this study were to evaluate fruit and vegetable consumption patterns, including intake of antioxidant-rich fruits and vegetables, provide education about benefits of consuming fruits and vegetables, expose participants to different varieties of fruits and vegetables, and improve fruit and vegetable consumption. Fifty-four adults (19 men/35 women; 44.7 +/- 12.1 y) were randomly assigned to one of three intervention groups. The control group received no intervention, the education group attended weekly nutrition lessons focused on benefits of fruit and vegetable consumption, and the fruit and vegetable group attended weekly nutrition lessons and received one serving of fruits and two servings of vegetables per day for 10 weeks. Intake of fruits and vegetables was assessed using semi-quantitative food frequency questionnaires and three-day food records. Findings suggested that while the majority of participants failed to consume the recommended number of servings of fruits and vegetables per day, nutrition education was helpful in improving the consumption frequency of antioxidant-rich fruits and vegetables among overweight and obese adults. PMID- 26850311 TI - The effect of academic stress and attachment stress on stress-eaters and stress undereaters. AB - It is well established that stress is related to changes in eating patterns. Some individuals are more likely to increase their overall food intake under conditions of stress, whereas others are more likely to consume less food when stressed. Attachment style has been linked to disordered eating and eating disorders; however, comparisons of eating behaviors under attachment versus other types of stress have yet to be explored. The present laboratory study examined the eating patterns in self-identified stress-undereaters and stress-eaters under various types of stress. More specifically, the study examined the effects of academic and attachment stress on calorie, carbohydrate and sugar consumption within these two groups. Under the guise of critiquing student films, university students viewed either one of two stress-inducing videos (academic stress or attachment stress, both designed to be emotionally arousing) or a control video (designed to be emotionally neutral), and their food intake was recorded. Results demonstrated that the video manipulations were effective in inducing stress. Differential patterns of eating were noted based on group and stress condition. Specifically, stress-undereaters ate fewer calories, carbohydrates and sugars than stress-eaters in the academic stress condition, but not in the attachment stress or control condition. Findings suggest that specific types of stressors may influence eating behaviors differently. PMID- 26850312 TI - Construct and criterion-related validation of nutrient profiling models: A systematic review of the literature. AB - Nutrient profiling (NP) is defined as the science of ranking foods according to their nutritional composition for the purpose of preventing disease or promoting health. The application of NP is ultimately to assist consumers to make healthier food choices, and thus provide a cost effective public health strategy to reduce the incidence of diet-related chronic disease. To our knowledge, no review has assessed the evidence to confirm the validity of NP models. We conducted a systematic review to investigate the construct and criterion-related validity of NP models in ranking food according to their nutritional composition for the purpose of preventing disease and promoting health. We searched peer-reviewed research published to 30 June 2015 and used PUBMED, Global Health (CABI), and SCOPUS databases. Within study bias was assessed using an adapted version of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies -2) tool for all diagnostic studies and the Cochrane Collaboration's Risk of Bias tool for all non diagnostic studies. The GRADE (Grades of Recommendation, Assessment, Development, and Evaluation) approach was used to guide our judgement of the quality of the body of evidence for each outcome measure. From a total of 83 studies, 69 confirmed the construct validity of NP models; however most of these studies contained methodological weaknesses. Six studies used objective external measures to confirm the criterion-related validity of NP models; which inherently improved quality. The overall quality of evidence on the accuracy of NP models was judged to be very low to moderate using the GRADE approach. Many carefully designed studies to establish both construct and criterion-related validity are necessary to authenticate the application of NP models and provide the evidence to support the current definition of NP. PMID- 26850313 TI - Development and evaluation of well-tolerated and tumor-penetrating polymeric micelle-based dry powders for inhaled anti-cancer chemotherapy. AB - Despite the direct access to the lung offered by the inhalation route, drug penetration into lung tumors could remain an important issue. In this study, folate-polyethylene glycol-hydrophobically-modified dextran (F-PEG-HMD) micelles were developed as an effective pulmonary drug delivery system to reach and penetrate lung tumors and cancer cells. The F-PEG-HMD micelles were able to enter HeLa and M109-HiFR, two folate receptor-expressing cancer cell lines, in vitro, and in vivo after administration by inhalation to orthotopic M109-HiFR lung tumor grafted mice. Paclitaxel-loaded F-PEG-HMD micelles characterized in PBS by a Z average diameter of ~50 nm and a zeta potential of ~-4 mV were prepared with an encapsulation efficiency of ~100%. The loaded micelles reduced HeLa and M109-HiFR cell growth, with half maximal inhibitory concentrations of 37 and 150 nM, respectively. Dry powders embedding the paclitaxel-loaded F-PEG-HMD micelles were developed by spray-drying. In vitro, good deposition profiles were obtained, with a fine particle fraction of up to 50% and good ability to re-disperse the micelles in physiological buffer. A polymeric micelle-based dry powder without paclitaxel was well-tolerated in vivo, as assessed in healthy mice by determination of total protein content, cell count, and cytokine IL-1beta, IL-6, and TNF-alpha concentrations in bronchoalveolar lavage fluids. PMID- 26850314 TI - Cremophor EL-based nanoemulsion enhances transcellular permeation of emodin through glucuronidation reduction in UGT1A1-overexpressing MDCKII cells. AB - Oral emodin, a natural anthraquinone and active component of many herbal medicines, is poorly bioavailable because of extensive first-pass glucuronidation. Here we aimed to prepare emodin nanoemulsion (EMO-NE) containing cremophor EL, and to assess its potential for enhancing transcellular absorption of emodin using UGT1A1-overexpressing MDCKII cells (or MDCK1A1 cells). EMO-NE was prepared using a modified emulsification technique and subsequently characterized by particle size, morphology, stability, and drug release. MDCKII cells were stably transfected with UGT1A1 using the lentiviral transfection approach. Emodin transport and metabolism were evaluated in Transwell-cultured MDCK1A1 cells after apical dosing of EMO-NE or control solution. The obtained EMO-NE (116 +/- 6.5 nm) was spherical and stable for at least 2 months. Emodin release in vitro was a passive diffusion-driven process. EMO-NE administration increased the apparent permeability of emodin by a 2.3-fold (p<0.001) compared to the pure emodin solution (1.2 * 10(-5) cm/s vs 5.3 * 10(-6) cm/s). Further, both apical and basolateral excretion of emodin glucuronide (EMO-G) were significantly decreased (>=56.5%, p<0.001) in EMO-NE group. This was accompanied by a marked reduction (57.4%, p<0.001) in total emodin glucuronidation. It was found that the reduced glucuronidation was due to inhibition of cellular metabolism by cremophor EL. Cremophor EL inhibited UGT1A1-mediated glucuronidation of emodin using the mixed type inhibition mechanism. In conclusion, cremophor EL-based nanoemulsion greatly enhanced transcellular permeation of emodin through inhibition of UGT metabolism. This cremophor EL-based nanoformulation may be a promising strategy to improve the oral bioavailability of emodin. PMID- 26850316 TI - Determination of the solubility of low volatility liquid organic compounds in water using volatile-tracer assisted headspace gas chromatography. AB - This study reports a new headspace gas chromatographic method (HS-GC) for the determination of water solubility of low volatility liquid organic compounds (LVLOs). The HS-GC analysis was performed on a set of aqueous solutions containing a range of concentrations of toluene-spiked (as a tracer) LVLOs, from under-saturation to over-saturation. A plot of the toluene tracer GC signal vs. the concentration of the LVLO results in two lines of different slopes that intersect at the concentration corresponding to the compound's solubility in water. The results showed that the HS-GC method has good precision (RSD <6.3%) and good accuracy, in which the relative deference between the data measured by the HS-GC method and the reference method were within 6.0%. The HS-GC method is simple and particularly suitable for measuring the solubility of LVLOs at elevated temperatures. This approach should be of special interest to those concerned about the impact of the presence of low-volatility organic liquids in waters of environmental and biological systems. PMID- 26850317 TI - Capillary-driven microfluidic paper-based analytical devices for lab on a chip screening of explosive residues in soil. AB - A novel microfluidic paper-based analytical device (MUPAD) was designed to filter, extract, and pre-concentrate explosives from soil for direct analysis by a lab on a chip (LOC) device. The explosives were extracted via immersion of wax printed MUPADs directly into methanol soil suspensions for 10min, whereby dissolved explosives travelled upwards into the MUPAD circular sampling reservoir. A chad was punched from the sampling reservoir and inserted into a LOC well containing the separation buffer for direct analysis, avoiding any further extraction step. Eight target explosives were separated and identified by fluorescence quenching. The minimum detectable amounts for all eight explosives were between 1.4 and 5.6ng with recoveries ranging from 53-82% from the paper chad, and 12-40% from soil. This method provides a robust and simple extraction method for rapid identification of explosives in complex soil samples. PMID- 26850318 TI - A new method for the rapid analysis of 1H-Pyrrole-2,5-diones (maleimides) in environmental samples by two-dimensional gas chromatography time-of-flight mass spectrometry. AB - Maleimides (1H-Pyrrole-2,5-diones) are monopyrrolic pigment derivatives with specific alkyl side chains that can be directly linked to their tetrapyrrole precursors, most notably chlorophylls and bacteriochlorophylls. These compounds can be used as palaeoenvironmental indicators such as algal productivity and redox conditions in ancient and modern aquatic systems. Here, we present a new method using two-dimensional gas chromatography time-of-flight mass spectrometry (GC * GC-ToF-MS), which enables the rapid analysis of maleimides in complex mixtures and different matrices (e.g. sediments and soils), therefore largely simplifying the previous intricate maleimide purification protocol. This method also reduces the potential for bias associated with partial losses due to low recovery and the high volatility of maleimides. The maleimide distributions and concentrations obtained by GC * GC-ToF-MS were reproducible and in agreement with the previously used purification procedure followed by analysis with traditional gas chromatography-mass spectrometry (GC-MS). The new method also resolved previously unrecognised, partial coelution of some maleimides with unknown compounds by quantification with the m/z 75 fragment ion. Furthermore, the higher sensitivity enabled the detection of previously unrecognised and preliminarily identified maleimides based on their relative retention times. The new, easier, rapid and more sensitive GC*GC-ToF-MS method greatly facilitates the analysis of maleimides in environmental samples to study tetrapyrrole degradation processes and will further the development of maleimides as biomarkers for palaeoenvironmental reconstructions. PMID- 26850319 TI - Allele-Specific Reduction of the Mutant Huntingtin Allele Using Transcription Activator-Like Effectors in Human Huntington's Disease Fibroblasts. AB - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an abnormal expansion of CAG repeats. Although pathogenesis has been attributed to this polyglutamine expansion, the underlying mechanisms through which the huntingtin protein functions have yet to be elucidated. It has been suggested that postnatal reduction of mutant huntingtin through protein interference or conditional gene knockout could prove to be an effective therapy for patients suffering from HD. For allele-specific targeting, transcription activator-like effectors (TALE) were designed to target single-nucleotide polymorphisms (SNP) in the mutant allele and packaged into a vector backbone containing KRAB to promote transcriptional repression of the disease-associated allele. Additional TALEs were packaged into a vector backbone containing heterodimeric FokI and were designed to be used as nucleases (TALEN) to cause a CAG-collapse in the mutant allele. Human HD fibroblasts were treated with each TALE-SNP or TALEN. Allele-expression was measured using a SNP-genotyping assay and mutant protein aggregation was quantified with Western blots for anti ubiquitin. The TALE-SNP and TALEN significantly reduced mutant allele expression (p < 0.05) when compared to control transfections while not affecting expression of the nondisease allele. This study demonstrates the potential of allele specific gene modification using TALE proteins, and provides a foundation for targeted treatment for individuals suffering from Huntington's or other genetically linked diseases. PMID- 26850315 TI - Unconventional aqueous humor outflow: A review. AB - Aqueous humor flows out of the eye primarily through the conventional outflow pathway that includes the trabecular meshwork and Schlemm's canal. However, a fraction of aqueous humor passes through an alternative or 'unconventional' route that includes the ciliary muscle, supraciliary and suprachoroidal spaces. From there, unconventional outflow may drain through two pathways: a uveoscleral pathway where aqueous drains across the sclera to be resorbed by orbital vessels, and a uveovortex pathway where aqueous humor enters the choroid to drain through the vortex veins. We review the anatomy, physiology and pharmacology of these pathways. We also discuss methods to determine unconventional outflow rate, including direct techniques that use radioactive or fluorescent tracers recovered from tissues in the unconventional pathway and indirect methods that estimate unconventional outflow based on total outflow over a range of pressures. Indirect methods are subject to a number of assumptions and generally give poor agreement with tracer measurements. We review the variety of animal models that have been used to study conventional and unconventional outflow. The mouse appears to be a promising model because it captures several aspects of conventional and unconventional outflow dynamics common to humans, although questions remain regarding the magnitude of unconventional outflow in mice. Finally, we review future directions. There is a clear need to develop improved methods for measuring unconventional outflow in both animals and humans. PMID- 26850320 TI - Coexisting cytomegalovirus infection in immunocompetent patients with Clostridium difficile colitis. AB - Cytomegalovirus (CMV) colitis usually occurs in immunocompromised patients with human immunodeficiency virus infection, organ transplantation, and malignancy receiving chemotherapy or ulcerative colitis receiving immunosuppressive agents. However, CMV colitis is increasingly recognized in immunocompetent hosts. Notably, CMV colitis coexisting with Clostridium difficile infection (CDI) in apparently healthy individuals has been published in recent years, which could result in high morbidity and mortality. CMV colitis is a rare but possible differential diagnosis in immunocompetent patients with abdominal pain, watery, or especially bloody diarrhea, which could be refractory to standard treatment for CDI. As a characteristic of CDI, however, pseudomembranous colitis may be only caused by CMV infection. Real-time CMV-polymerase chain reaction (PCR) for blood and stool samples may be a useful and noninvasive diagnostic strategy to identify CMV infection when treatment of CDI eventually fails to show significant benefits. Quantitative CMV-PCR in mucosal biopsies may increase the diagnostic yield of traditional histopathology. CMV colitis is potentially life-threatening if severe complications occur, such as sepsis secondary to colitis, massive colorectal bleeding, toxic megacolon, and colonic perforation, so that may necessitate pre-emptive antiviral treatment for those who are positive for CMV PCR in blood and/or stool samples while pending histological diagnosis. PMID- 26850321 TI - Molecular prevalence and estimated risk of cutaneous leishmaniasis in Libya. AB - BACKGROUND/PURPOSE: Cutanoeus leishmaniasis (CL) is an endemic disease in the Mediterranean area including Libya. The aim of the present study is to detect the prevalent Leishmania species obtained from smeared cutaneous lesions in addition to studying the diverse sociodemographic risk factors of the reported cases from different provinces of Libya. METHODS: A total of 250 archived microscopic slides from clinically suspected cases of CL attending the leishmaniasis clinic in the Dermatology Department, Tripoli Central Hospital, Tripoli, Libya, were microscopically examined. Leishmania-DNA was amplified using combined polymerase chain reaction (PCR) targeting kinetoplast-DNA (kDNA) and ribosomal internal transcribed spacer 1 (ITS1)-DNA with restriction fragment length polymorphism analysis for direct Leishmania species identification. RESULTS: Using kDNA and ITS1-PCR, 22.5% and 20% of cases were positive, respectively. Only 14.4% of cases were positive using microscopy. Nominating ITS1-PCR as the reference standard, kDNA-PCR assay was highly sensitive while microscopy was 100% specific but of limited sensitivity (72%) with a substantial agreement and an overall accuracy of 94.4%. Leishmania major and Leishmania tropica were the predominant species reported from the north-western provinces including Tripoli, Zintan, and Gharyan with their related subprovinces; Asabaa, Mizdan, Alkawasem, and Alorban. CL prevailed more among men and residents of rural areas. House wives and students were the most affected professions. Children were the least affected, while the middle-aged were the most affected age group. CONCLUSION: L. major and L. tropica are the predominant species in the north-western regions of Libya. ITS1-PCR restriction fragment length polymorphism assay offered a sensitive, specific, and faster diagnostic method especially with negative parasitologic examination. PMID- 26850322 TI - Components of the lectin pathway of complement activation in paediatric patients of intensive care units. AB - Infections are a major cause of childhood mortality. We investigated components of the lectin pathway of complement activation in the context of sepsis at both genetic and protein levels in neonates, infants and older children. Major components of the lectin pathway and two genes for Toll-like receptors were studied in 87 neonates with confirmed sepsis and compared with 40 babies with infections who did not develop sepsis (disease controls) and 273 infection-free neonatal controls. A second cohort comprised 47 older children with sepsis and 87 controls. Low MBL-conferring genotypes (LXA/O+O/O) were more frequent in sepsis patients than in healthy controls but no significant differences in the frequency of SNPs of other lectin pathway genes (FCN1, FCN2, FCN3, MASP1/3, MASP2) or TLR receptor genes (TLR2, TLR4) were found. One case of primary MASP-2 deficiency was found among healthy pre-terms and one neonate suffering from SIRS was heterozygous for the rare FCN1 gene mutation, +6658 G>A. Generally, sepsis was associated with low serum MBL and low ficolin-2 concentrations on admission. Among neonates, ficolin-1 and MASP-2 levels were elevated in sepsis relative to healthy, but not disease, controls. Unlike neonates, ficolin-3 and MASP-2 levels were lower in older patients than in healthy controls while no difference was found for ficolin-1. With the possible exception of MBL, inherited lectin pathway insufficiencies do not seem to predispose to sepsis, rather changes in protein concentrations reflect alterations in disease course. PMID- 26850323 TI - High expression of CD38, CD69, CD95 and CD154 biomarkers in cultured peripheral T lymphocytes correlates with an increased risk of acute rejection in liver allograft recipients. AB - The mayor goal still outstanding into the solid organ transplantation field involves the search of surrogate biomarkers able to predict several clinical events, such as acute rejection (AR) or opportunistic infection. In the present multicenter study, a series of interesting surface antigens with important activator or inhibitory immune functions on cultured peripheral T cells were monitored in liver transplant recipients drawn at baseline and up to one year after transplantation. Sixty-four patients were included in the multicenter study during 3 years. Pre- and post-transplantation surface antigens levels displayed significant differences between AR and non acute rejection (NAR) groups, and also this differential expression was used to construct a risk predictive model based on a composite panel of outcome biomarkers (CD38, CD69, CD95 and CD154). The model was able to stratify these patients at high risk of AR. These preliminary results could provide basic information to improve the immunosuppressive treatment and it might better help to predict AR episodes. PMID- 26850324 TI - A TILLING approach to generate broad-spectrum resistance to potyviruses in tomato is hampered by eIF4E gene redundancy. AB - Genetic resistance to pathogens is important for sustainable maintenance of crop yields. Recent biotechnologies offer alternative approaches to generate resistant plants by compensating for the lack of natural resistance. Tomato (Solanum lycopersicum) and related species offer a model in which natural and TILLING induced potyvirus resistance alleles may be compared. For resistance based on translation initiation factor eIF4E1, we confirm that the natural allele Sh eIF4E1(PI24)-pot1, isolated from the wild tomato species Solanum habrochaites, is associated with a wide spectrum of resistance to both potato virus Y and tobacco etch virus isolates. In contrast, a null allele of the same gene, isolated through a TILLING strategy in cultivated tomato S. lycopersicum, is associated with a much narrower resistance spectrum. Introgressing the null allele into S. habrochaites did not extend its resistance spectrum, indicating that the genetic background is not responsible for the broad resistance. Instead, the different types of eIF4E1 mutations affect the levels of eIF4E2 differently, suggesting that eIF4E2 is also involved in potyvirus resistance. Indeed, combining two null mutations affecting eIF4E1 and eIF4E2 re-establishes a wide resistance spectrum in cultivated tomato, but to the detriment of plant development. These results highlight redundancy effects within the eIF4E gene family, where regulation of expression alters susceptibility or resistance to potyviruses. For crop improvement, using loss-of-function alleles to generate resistance may be counter productive if they narrow the resistance spectrum and limit growth. It may be more effective to use alleles encoding functional variants similar to those found in natural diversity. PMID- 26850325 TI - Acute Myeloid Leukemia: analysis of epidemiological profile and survival rate. AB - OBJECTIVE: To describe the epidemiological profile and the survival rate of patients with acute myeloid leukemia (AML) in a state reference pediatric hospital. METHOD: Clinical-epidemiological, observational, retrospective, descriptive study. The study included new cases of patients with AML, diagnosed between 2004 and 2012, younger than 15 years. RESULTS: Of the 51 patients studied, 84% were white; 45% were females and 55%, males. Regarding age, 8% were younger than 1 year, 47% were aged between 1 and 10 years, and 45% were older than 10 years. The main signs/symptoms were fever (41.1%), asthenia/lack of appetite (35.2%), and hemorrhagic manifestations (27.4%). The most affected extra medullary site was the central nervous system (14%). In 47% of patients, the white blood cell (WBC) count was below 10,000/mm(3) at diagnosis. The minimal residual disease (MRD) was less than 0.1%, on the 15th day of treatment in 16% of the sample. Medullary relapse occurred in 14% of cases. When comparing the bone marrow MRD with the vital status, it was observed that 71.42% of the patients with type M3 AML were alive, as were 54.05% of those with non-M3 AML. The death rate was 43% and the main proximate cause was septic shock (63.6%). CONCLUSIONS: In this study, the majority of patients were male, white, and older than 1 year. Most patients with WBC count <10,000/mm(3) at diagnosis lived. Overall survival was higher in patients with MRD <0.1%. The prognosis was better in patients with AML-M3. PMID- 26850326 TI - Short-term and oncologic outcomes of laparoscopic and open complete mesocolic excision and central ligation. AB - PURPOSE: To evaluate the pathologic, short-term and oncologic outcomes of laparoscopic and open complete mesocolic excision (CME) and central ligation for right-sided colon cancer. METHODS: All patients (n = 215) underwent elective CME either by open surgery (n = 99) or laparoscopy (n = 116). RESULTS: Mean number of retrieved lymph nodes (31 vs. 27, p = 0.012) was greater in the open CME group. Between the open and laparoscopic CME groups, there were no differences of length of the specimen (44.3 cm and 43.2 cm), ileum (14 cm and 13.3 cm), or colon (30.3 cm and 29.8 cm), respectively. Proximal and distal margins were similar. Mean operative time was similar between the open and laparoscopic CME groups (175 min vs. 178 min). The rate of 30-day postoperative complications (36.4% vs. 23.3%, p = 0.036) was higher in the open CME group. There were no differences in 3-year overall survival rates (86.9% vs. 95.5% in stage II disease and 70.2% vs. 90.7% in stage III disease) or recurrence-free survival rates (84.5% vs. 84.8% in stage II disease and 64.2% vs. 68.9% in stage III disease) between the open and laparoscopic CME groups. CONCLUSIONS: Pathologic (specimen lengths, resection margin lengths, number of lymph nodes, and R0 resection) and oncologic outcomes of the laparoscopic CME group were comparable. Moreover, laparoscopic CME conferred short-term benefits in terms of lower rates of postoperative complications, reduced time to soft diet, and reduced length of hospital stay. Based on these results, laparoscopic CME can be considered as a routine elective approach for right-sided colon cancer. PMID- 26850327 TI - Retinal ischaemia and delayed fibrovascular proliferation associated with an optic nerve coloboma. AB - CASE REPORT: A patient with a left optic nerve coloboma with late development (at 15 years of age) of vitreoretinal fibrovascular proliferation and tractional retinal detachment (TRD). Sectorial retinal photocoagulation was performed with regression of the proliferative tissue and exudation. DISCUSSION: Congenital optic nerve anomalies may be associated with significant retinal avascularity, ischaemia and late fibrovascular proliferation. Laser is effective for regression of the neovascular tissue and preventing TRD progression. PMID- 26850328 TI - The presence of CFH, HTRA1, ARMS2, VEGF-A and VEGF-R and the appearance of age related macular degeneration sub-types. AB - OBJECTIVE: To demonstrate the genetic influence in the onset of the different age related macular disease (AMD) subtypes by analysing the genotype distribution of CFH, ARMS2, HTRA1, VEGF-A and VEGF-R polymorphisms in patients with neovascular and atrophic AMD. MATERIALS AND METHODS: The study was conducted on 101 consecutive patients with AMD diagnosis (74 exudative, 27 atrophic) following Wisconsin international classification criteria. The CFH rs1410996, ARMS2 rs10940923, VEGF-A rs833061, rs699947, and VEGF-R rs2071559 polymorphisms were analysed using real time PCR with taqman probes, and HTRA1 rs112000638 using restriction endonucleases digestion. A study was made of the genotype distribution of the different polymorphisms in our group of patients with neovascular AMD and those with the atrophic type, and a comparison was made of the results for each one of the genes studied. RESULTS: No statistically significant differences (P>.05) were found in the genotype distribution of the different polymorphisms between patients with neovascular AMD and patients with atrophic AMD in our population, although the "risk" genotypes tended to appear more frequently in patients with neovascular AMD, despite the lack of statistical significance. CONCLUSIONS: Allelic variants of CFH, ARMS2, HTRA1, VEGF-A or VEGF R genes are not associated with the different AMD subtypes. This suggests that, although the polymorphisms seem to be associated with the disease susceptibility, they are not involved in the onset of the different clinical variants of AMD. Further studies in different populations, and with a larger cohort of patients, are needed to confirm these results. PMID- 26850329 TI - Appropriate positioning of the NAVA catheter. PMID- 26850330 TI - Rapid response teams improve outcomes: no. PMID- 26850331 TI - Rapid response teams improve outcomes: we are not sure. PMID- 26850332 TI - Rapid response teams improve outcomes: yes. PMID- 26850333 TI - Oral mucosal adverse events with chlorhexidine 2% mouthwash in ICU. PMID- 26850334 TI - Unfinished nursing care: An important performance measure for nursing care systems. AB - Performance measurement is a core administrative function and an essential component of organizational quality programs. The prevalence of performance measurement initiatives increased significantly after the release of the Institute of Medicine series on quality. Nursing performance measures are limited in their scope, resulting in an underrepresentation of process measures. Development of performance indicators that reflect how effectively organizational units actually transform nursing resources into nursing services should be a high priority. Unfinished nursing care is a nursing process performance measure that reflects the complexity of the nursing care environment and can be useful in comparing process performance across systems and organizations. Unfinished nursing care is congruent with many of the National Quality Forum requirements for endorsement and warrants further refinement as an important nurse-sensitive performance measure. PMID- 26850335 TI - Responses of three very large inducible GTPases to bacterial and white spot syndrome virus challenges in the giant fresh water prawn Macrobrachium rosenbergii. AB - Interferons (IFNs) are cytokines secreted by cells in response to invasion by pathogens, such as viruses, bacteria, parasites, or tumor cells. Very large inducible GTPases (VLIG) are the latest IFN-inducible GTPase family to be discovered and are the largest known GTPases of any species. However, VLIG proteins from invertebrates have yet to be characterized. In this study, three forms of VLIGs designated as MrVLIG1, MrVLIG2, and MrVLIG3 were cloned from the giant fresh water prawn Macrobrachium rosenbergii. MrVLIG1 has a 5445 bp open reading frame (ORF) encoding an 1814-amino acid protein. The complete nucleotide sequence of MrVLIG2 cDNA is 7055 bp long consisting of a 5757 bp ORF encoding a protein with 1918 amino acids. The full length of the MrVLIG3 gene consists of 5511 bp with a 3909 bp ORF encoding a peptide with 1302 amino acids. BLASTP and phylogenetic tree analyses showed that the three MrVLIGs are clustered into one subgroup and, together with other vertebrate VLIGs, into a branch. Tissue distribution analysis indicated that the mRNAs of the three MrVLIGs were widely expressed in almost all detected tissues, including the hemocytes, heart, hepatopancreas, gills, stomach, and intestine, with the highest expression in the hepatopancreas. They were also detected in the intestine but with relatively low expression levels. Quantitative real-time RT-PCR analysis showed that the mRNA transcripts of the MrVLIGs in the hepatopancreas were significantly expressed at various time points after infection with Vibrio parahaemolyticus and white spot syndrome virus. In summary, the three isoforms of VLIG genes participate in the innate immune response of the shrimps to bacterial and viral infections. PMID- 26850336 TI - Knockdown of DNMT1 and DNMT3a Promotes the Angiogenesis of Human Mesenchymal Stem Cells Leading to Arterial Specific Differentiation. AB - Human mesenchymal stem cells (hMSCs) possess the potential to differentiate into endothelial cells (EC). DNA methylation plays an important role in cell differentiation during development. However, the role of the DNA methyltransferases Dnmt1 and Dnmt3a in specific arterial differentiation of hMSCs is not clear. Here, we show that the CpG islands in the promoter regions of the EC specification and arterial marker genes were highly methylated in hMSCs based on bisulfite genomic sequencing. Treatment with the DNMT inhibitor 5-aza-dc induced the reactivation of EC specification and arterial marker genes by promoting demethylation of these genes as well as stimulating tube-like structure formation. The hMSCs with stable knockdown of Dnmt1/Dnmt3a were highly angiogenic and expressed several arterial specific transcription factors and marker genes. A Matrigel plug assay confirmed that Dnmt1/Dnmt3a stable knockdown hMSCs enhanced blood vessel formation compared with WT MSCs. We also identified that the transcription factor E2F1 could upregulate the transcription of arterial marker genes by binding to the promoters of arterial genes, suggesting its critical role for arterial specification. Moreover, miRNA gain/loss-of-function analyses revealed that miR152 and miR30a were involved in endothelial differentiation of hMSCs by targeting Dnmt1 and Dnmt3a, respectively. Taken together, these data suggest that Dnmt1 and Dnmt3a are critical regulators for epigenetic silencing of EC marker genes and that E2F1 plays an important role in promoting arterial cell determination. Stem Cells 2016;34:1273-1283. PMID- 26850337 TI - Integrative discovery of CD98 as a melanoma biomarker. PMID- 26850338 TI - Spanish adaptation of the recommendations for the appropriate use of social networks in urology of the European Association of Urology. AB - OBJECTIVE: To adapt to Spanish the recommendations for the appropriate use of social media (SoMe) in the urological setting prepared by the European Association of Urology (EAU). ACQUISITION OF EVIDENCE: The use of SoMe has become fairly popular in the international urological community. Due to the nature of the medical content shared among healthcare professionals through SoMe, however, there is the risk of medical and legal problems. For this reason, various international urological associations such as the American Urological Association, the British Association of Urological Surgeons and EAU have published their recommendations for the appropriate use of social media. Efforts have been made to adapt and summarise the recommendations of the EAU in Spanish and to publish them in Actas Urologicas Espanolas (@actasurologicas), the official journal of the Spanish Urological Association (@InfoAEU) and the American Confederation of Urology (@CAU_URO). SYNTHESIS OF THE EVIDENCE: SoMe include well-known platforms such as Twitter, Facebook and YouTube, which have undoubtedly changed the way in which people communicate and interact. SoMe offer clear advantages for communicating between professionals, working in teams, disseminating knowledge and creating professional profiles and are increasingly used by patients and healthcare practitioners. The introduction of SoMe in the urological community has started a revolution in how scientific articles are shared, how people participate in congresses and how international urological associations communicate with their followers. However, SoMe is generally an open public setting, with potential risks for confidentiality and the doctor-patient relationship due to the nature of the shared information. The present recommendations include tools for creating professional profiles, protecting confidentiality and creating honest and responsible content. CONCLUSIONS: SoMe represents a fascinating area for the communication and dissemination of knowledge, with considerable applicability in health care and the urological community. New efforts are being directed to extend the use of social media in the urological community, measuring its actual academic impact and standardising the language employed. PMID- 26850339 TI - Artemisinin (Qinghaosu), Nobel Prize, anti-malaria, and beyond. PMID- 26850340 TI - Pharmaceutical innovation and advancement of Clinical therapy and public health: enlightenment from artemisinin development. PMID- 26850341 TI - Artemisinin: A wonder drug from Chinese natural medicines. PMID- 26850342 TI - Red ginseng and cancer treatment. AB - The ginseng family, including Panax ginseng (Asian ginseng), Panax quinquefolius (American ginseng), and Panax notoginseng (notoginseng), is commonly used herbal medicine. White ginseng is prepared by air-drying after harvest, while red ginseng is prepared by a steaming or heating process. The anticancer activity of red ginseng is significantly increased, due to the production of active anticancer ginsenosides during the steaming treatment, compared with that of white ginseng. Thus far, anticancer studies have been mostly focused on Asian ginseng. In this article, we review the research progress made in the anticancer activities of red Asian ginseng, red American ginseng and red notoginseng. The major anticancer mechanisms of red ginseng compounds include cell cycle arrest, induction of apoptosis/paraptosis, and inhibition of angiogenesis. The structure function relationship analysis has revealed that the protopanaxadiol group ginsenosides have more potent effects than the protopanaxatriol group. Sugar molecules in ginsenosides inversely impact the antiproliferative potential of these compounds. In addition, ginsenoside stereoselectivity and double bond position also influence the anticancer activity. Future studies should focus on characterizing active red ginseng derivatives as potential anticancer drugs. PMID- 26850343 TI - Phytochemistry, pharmacology, and clinical trials of Morus alba. AB - The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties. PMID- 26850344 TI - Delonix regia: historic perspectives and modern phytochemical and pharmacological researches. AB - Delonix regia (Bojer ex Hook) Raffin (Fabaceae), also known as flame of forest, is a semi-deciduous tree, distributed throughout Madagascar, India, Africa, and Northern Australia. Various parts of the plant are traditionally used for the treatment of different ailments such as inflammation, rheumatism, bronchitis, diabetes, anemia, fever, gynecological disorders, and pneumonia. The plant possess antioxidant, hepatoprotective, gastroprotective, wound healing, antiarthritic, larvicidal, antimalarial, antiemetic, antibacterial, antifungal, antiinflammatory, analgesic, antidiarrhoeal, antiheamolytic, diuretic, and anthelmintic activities. This review is an up-to-date compilation on its traditional uses in context to phytochemical and pharmacological perspectives. PMID- 26850345 TI - Silibinin alleviates N-nitrosodimethylamine-induced glutathione dysregulation and hepatotoxicity in rats. AB - The present study was designed to evaluate the hepatoprotective and antioxidant potentials of silibinin (SBN) against N-nitrosodimethylamine (DMN)-induced toxic insults in the rat liver. The liver damage was induced in Wistar albino rats by repeated administration of DMN (10 mg.kg(-1) b.w., i.p.) on 3 consecutive days per week for 3 weeks. SBN (100 mg.kg(-1) b.w., p.o.) was given daily to the DMN treated rats for two weeks. The marker enzymes of liver toxicity and second-line enzymic and non-enzymic antioxidants were evaluated in serum and liver tissues before and after SBN treatment. Histopathology of the liver was evaluated by H & E staining. The DMN treatment produced a progressive increase in all the serum marker enzymes (AST, ALT, ALP, LDH, and gamma-GT), peaking on Day 21. This treatment produced highly significant decreases in all the second-line antioxidant parameters (GSH, GST, GR, GPx, and vitamins C and E). The SBN treatment significantly reversed the DMN-induced damages, towards normalcy. Histopathological studies confirmed the development of liver toxicity in DMN treated rats, which was reversed by SBN treatment in corroboration with the aforementioned biochemical results, indicating the hepatoprotective and antioxidant properties of SBN. In conclusion, the DMN-induced degenerative changes in the liver were alleviated by SBN treatment and this protective ability may be attributed to its antioxidant, free radical scavenging, and membrane stabilizing properties. PMID- 26850346 TI - Baicalin attenuates high fat diet-induced insulin resistance and ectopic fat storage in skeletal muscle, through modulating the protein kinase B/Glycogen synthase kinase 3 beta pathway. AB - Insulin resistance is the pathophysiological basis of many diseases. Overcoming early insulin resistance highly significant in prevention diabetes, non-alcoholic fatty liver, and atherosclerosis. The present study aimed at evaluating the therapeutic effects of baicalin on insulin resistance and skeletal muscle ectopic fat storage in high fat diet-induced mice, and exploring the potential molecular mechanisms. Insulin resistance in mice was induced with a high fat diet for 16 weeks. Animals were then treated with three different doses of baicalin (100, 200, and 400 mg.kg(-1).d(-1)) for 14 weeks. Fasting blood glucose, fasting serum insulin, glucose tolerance test (GTT), insulin tolerance test (ITT), and skeletal muscle lipid deposition were measured. Additionally, the AMP-activated protein kinase/acetyl-CoA carboxylase and protein kinase B/Glycogen synthase kinase 3 beta pathways in skeletal muscle were further evaluated. Baicalin significantly reduced the levels of fasting blood glucose and fasting serum insulin and attenuated high fat diet induced glucose tolerance and insulin tolerance. Moreover, insulin resistance was significantly reversed. Pathological analysis revealed baicalin dose-dependently decreased the degree of the ectopic fat storage in skeletal muscle. The properties of baicalin were mediated, at least in part, by inhibition of the AMPK/ACC pathway, a key regulator of de novo lipogenesis and activation of the Akt/GSK-3beta pathway, a key regulator of Glycogen synthesis. These data suggest that baicalin, at dose up to 400 mg.kg( 1).d(-1), is safe and able to attenuate insulin resistance and skeletal muscle ectopic fat storage, through modulating the skeletal muscle AMPK/ACC pathway and Akt/GSK-3beta pathway. PMID- 26850347 TI - Non-alkaloid constituents of Vinca major. AB - The present study was designed to investigate the non-alkaloid compounds from the leaves and stems of Vinca major cultivated in Yunnan Province, China. The compounds were isolated using chromatographic techniques. The structures were elucidated by 1D- and 2D-NMR spectroscopic methods in combination with UV, IR, and MS analyses. The 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-scavenging activity of Compounds 1-7 were evaluated. One new iridoid glycoside (compound 1), together with 11 known compounds, were isolated from Vinca major. Compounds 1, 5, and 6 showed moderate DPPH-scavenging activity, with IC50 values being 70.6, 32.8, and 62.2 MUmol.L(-1), respectively. In conclusion, compound 1 is a newly identified iridoid glycoside with moderate antioxidant activity. PMID- 26850348 TI - Anti-inflammatory iridoids from the stems of Cistanche deserticola cultured in Tarim Desert. AB - In order to determine the chemical constituents of Cistanche deserticola cultured in Tarim desert, a systematically phytochemical investigation was carried out. The constituents were isolated by silica gel, Sephadex LH-20, MCI gel, ODS column chromatography, and semi-preparative HPLC. Their structures were determined on the basis of MS and NMR spectroscopic analyses, by chemical methods, and/or comparison with literature data. The anti-inflammatory activities of the isolates were evaluated for their inhibitory effects on the lipopolysaccharide (LPS) induced nitric oxide (NO) production in BV-2 mouse microglial cells. Nine iridoids were isolated and identified as cistadesertoside A (1), cistanin (2), cistachlorin (3), 6-deoxycatalpol (4), gluroside (5), kankanoside A (6), ajugol (7), bartsioside (8), and 8-epi-loganic acid (9). Compound 9 exhibited potent inhibition on the NO production with an IC50 value being 5.2 MUmol.L(-1), comparable to the positive control quercetin (4.3 MUmol.L(-1)). Compound 1 was a new iridoid, and compounds 5, 6, and 8 were isolated from this species for the first time. PMID- 26850349 TI - Dynamic changes of flavonoids in Actinidia valvata leaves at different growing stages measured by HPLC-MS/MS. AB - Flavonoids are a large group of phenolic secondary metabolites havinga wide range of biochemical and pharmacological effects. Quantitative analysis of flavonoid profiles in the genus Actinidia, which has not been intensively conducted, is useful to a better understanding of the pattern and distribution of flavonoids. In the present work, a liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) method was developed to profile the flavonoids, which was then used to determine the dynamic change of 17 biologically active flavonoids in the leaves of Actinidia valvata at the main growing stages, including glucuronides and acylated di- and triglycosides of flavonoids. The contents of flavonoid triglycosides were significantly higher than other flavonoids. The highest concentrations of kaemperol glycosides were observed in June, while other flavonoids showed highest concentrations in October. On the other hand, the contents of four isorhamnetin glycosides were increased sharply in September to October. The flavonoid profiles seem to be related to temperature, UV-B, and water deficit. Further studies are required to examine the functions of flavonoids in the Actinidia valvata and the underlying molecular mechanisms of actions. PMID- 26850350 TI - Impact of parameter fluctuations on the performance of ethanol precipitation in production of Re Du Ning Injections, based on HPLC fingerprints and principal component analysis. AB - The present study was designed to determine the relationships between the performance of ethanol precipitation and seven process parameters in the ethanol precipitation process of Re Du Ning Injections, including concentrate density, concentrate temperature, ethanol content, flow rate and stir rate in the addition of ethanol, precipitation time, and precipitation temperature. Under the experimental and simulated production conditions, a series of precipitated resultants were prepared by changing these variables one by one, and then examined by HPLC fingerprint analyses. Different from the traditional evaluation model based on single or a few constituents, the fingerprint data of every parameter fluctuation test was processed with Principal Component Analysis (PCA) to comprehensively assess the performance of ethanol precipitation. Our results showed that concentrate density, ethanol content, and precipitation time were the most important parameters that influence the recovery of active compounds in precipitation resultants. The present study would provide some reference for pharmaceutical scientists engaged in research on pharmaceutical process optimization and help pharmaceutical enterprises adapt a scientific and reasonable cost-effective approach to ensure the batch-to-batch quality consistency of the final products. PMID- 26850351 TI - Heterometopus meisterfeldi nov. gen., nov. spec. (Protozoa, Ciliophora), a new metopid from Australia. AB - Using standard methods, I describe Heterometopus meisterfeldi nov. gen., nov. spec., a new armophorean ciliate from dry soil of the bed of the Fogg Dam in northern Australia. It appeared in the non-flooded Petri dish culture three weeks after soil re-wetting, i.e., when the bottom zone of the culture became anaerobic. The new genus is characterized by a cylindroid body and a short, slightly oblique, J-shaped adoral zone extending only ventrally and about one third of body length. The species has an average size of 140*30MUm and has 23 ciliary rows, 30 adoral polykinetids, and 25 false kineties in the perizonal stripe. Metopus palaeformis, as redescribed by Foissner et al. (2002) and in the present paper, shows very similar characteristics and is thus transferred to the new genus: Heterometopus palaeformis (Kahl, 1927) nov. comb. Heterometopus meisterfeldi and H. palaeformis differ by body size (~140*30 vs. 100*20 in vivo), the shape of the macronucleus (ellipsoid, ~2:1 vs. elongate ellipsoid, ~3:1), the width of the side-stripe (12MUm vs. 4MUm), the number of false kineties in the perizonal stripe (25 vs. 14), and the number of adoral polykinetids (~30 vs. ~20). Very likely, several species from Kahl's Metopus groups II and III belong to Heterometopus but a transfer should await detailed redescriptions. Heterometopus meisterfeldi belongs very likely to the family Metopidae. The short, J-shaped adoral zone of polykinetids highly resembles the blepharismid genera Pseudoblepharisma and Blepharisma. PMID- 26850352 TI - A Q-backpropagated time delay neural network for diagnosing severity of gait disturbances in Parkinson's disease. AB - Parkinson's disease (PD) is a movement disorder that affects the patient's nervous system and health-care applications mostly uses wearable sensors to collect these data. Since these sensors generate time stamped data, analyzing gait disturbances in PD becomes challenging task. The objective of this paper is to develop an effective clinical decision-making system (CDMS) that aids the physician in diagnosing the severity of gait disturbances in PD affected patients. This paper presents a Q-backpropagated time delay neural network (Q BTDNN) classifier that builds a temporal classification model, which performs the task of classification and prediction in CDMS. The proposed Q-learning induced backpropagation (Q-BP) training algorithm trains the Q-BTDNN by generating a reinforced error signal. The network's weights are adjusted through backpropagating the generated error signal. For experimentation, the proposed work uses a PD gait database, which contains gait measures collected through wearable sensors from three different PD research studies. The experimental result proves the efficiency of Q-BP in terms of its improved classification accuracy of 91.49%, 92.19% and 90.91% with three datasets accordingly compared to other neural network training algorithms. PMID- 26850353 TI - Isolation of the monooxygenase complex from Rhipicephalus (Boophilus) microplus - clues to understanding acaricide resistance. AB - The monooxygenase complex is composed of three key proteins, a cytochrome P450 (CYP), the cytochrome P450 oxidoreductase (CPR) and cytochrome b5 and plays a key role in the metabolism and detoxification of xenobiotic substances, including pesticides. In addition, overexpression of these components has been linked to pesticide resistance in several important vectors of disease. Despite this, the monooxygenase complex has not been isolated from the Southern cattle tick Rhipicephalus (Boophilus) microplus, a major disease vector in livestock. Using bioinformatics 115 transcriptomic sequences were analyzed to identify putative pesticide metabolizing CYPs. RACE-PCR was used to amplify the full length sequence of one CYP; CYP3006G8 which displays a high degree of homology to members of the CYP6 and 9 subfamilies, known to metabolize pyrethroids. mRNA expression levels of CYP3006G8 were investigated in 11 strains of R. microplus with differing resistance profiles by qPCR, the results of which indicated a correlation with pyrethroid metabolic resistance. In addition to this gene, the sequences for CPR and cytochrome b5 were also identified and subsequently isolated from R. microplus using PCR. CYP3006G8 is only the third CYP gene isolated from R. microplus and the first to putatively metabolize pesticides. The initial results of expression analysis suggest that CYP3006G8 metabolizes pyrethroids but further biochemical characterization is required to confirm this. Differences in the kinetic parameters of human and mosquito CPR in terms of NADPH binding have been demonstrated and could potentially be used to design species specific pesticides. Similar differences in the tick CPR would confirm that this is a characteristic of heamatophagous arthropods. PMID- 26850357 TI - Defining immunological dysfunction in sepsis: A requisite tool for precision medicine. AB - OBJECTIVES: Immunological dysregulation is now recognised as a major pathogenic event in sepsis. Stimulation of immune response and immuno-modulation are emerging approaches for the treatment of this disease. Defining the underlying immunological alterations in sepsis is important for the design of future therapies with immuno-modulatory drugs. METHODS: Clinical studies evaluating the immunological response in adult patients with Sepsis and published in PubMed were reviewed to identify features of immunological dysfunction. For this study we used key words related with innate and adaptive immunity. RESULTS: Ten major features of immunological dysfunction (FID) were identified involving quantitative and qualitative alterations of [antigen presentation](FID1), [T and B lymphocytes] (FID2), [natural killer cells] (FID3), [relative increase in T regulatory cells] (FID4), [increased expression of PD-1 and PD-ligand1](FID5), [low levels of immunoglobulins](FID6), [low circulating counts of neutrophils and/or increased immature forms in non survivors](FID7), [hyper-cytokinemia] (FID8), [complement consumption] (FID9), [defective bacterial killing by neutrophil extracellular traps](FID10). CONCLUSIONS: This review article identified ten major features associated with immunosuppression and immunological dysregulation in sepsis. Assessment of these features could help in utilizing precision medicine for the treatment of sepsis with immuno-modulatory drugs. PMID- 26850356 TI - Generation and application of ssDNA aptamers against glycolipid antigen ManLAM of Mycobacterium tuberculosis for TB diagnosis. AB - The development of effective Mycobacterial antigen diagnostic reagents remains a high priority. Mannose-capped lipoarabinomannan (ManLAM) is a lipoglycan serving as a major cell wall component. ManLAM is also an early released antigen in the blood circulation system during Mycobacteria tuberculosis (M.tb) infection and is a perfect target antigen for TB diagnosis. In this study, ssDNA aptamers "antibodies" against ManLAM of the predominant clinical epidemic M.tb Beijing genotype strains were generated by the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) technique. The selected single aptamer T9 demonstrated the highest specificity and binding affinity, with an equilibrium dissociation constant (Kd) of 668 +/- 159 nmol/L. We further detected ManLAM antigens in serum and sputum samples from active pulmonary tuberculosis (aPTB) patients, extrapulmonary TB (EPTB) patients and healthy donors by using a T9 based enzyme-linked oligonucleotide assay (ELONA). The results showed that the specificity and sensitivity were 95.31% and 83.00% (for 100 aPTB serum samples), 98.70% and 92.71% (for 96 aPTB sputum samples), and 94.44% and 88.71% (for 62 EPTB serum samples), respectively. A good correlation was observed between the T9 aptamer-based ELONA and the clinical T-SPOT.TB. Thus, T9 based ELONA has potentials for diagnosis of TB, including inactive TB, smear-negative TB, EPTB, and TB with immunodeficiency, and assist the diagnosis of LTBI albeit it could not distinguish LTBI and active TB. PMID- 26850358 TI - Differences in Bordetella pertussis DNA load according to clinical and epidemiological characteristics of patients with whooping cough. AB - OBJECTIVE: To identify associations between nasopharyngeal Bordetella pertussis DNA load and clinical and epidemiological characteristics and evaluate DNA load prognostic value in pertussis severity. METHODS: Prospective observational multi centre study including nasopharyngeal samples positive to pertussis DNA by real time PCR collected from children and adult patients in more than 200 health centres of Catalonia (Spain) during 2012-2013. RESULTS: B. pertussis load was inversely correlated with age (rho = -0.32, p < 0.001), time to diagnosis (rho = 0.33, p < 0.001) and number of symptoms (rho = 0.13, p = 0.002). Median bacterial load was significantly higher in inpatients versus outpatients (4.91 vs. 2.55 log10 CFU/mL, p < 0.001), patients with complications versus those without (6.05 vs. 2.82 log10 CFU/mL, p < 0.001), disease incidence in summer and autumn versus spring and winter (3.50 vs. 2.21 log10 CFU/mL, p = 0.002), and unvaccinated partially vaccinated patients versus vaccinated (4.20 vs. 2.76 log10 CFU/mL, p = 0.004). A logistic regression model including bacterial load and other candidate prognostic factors showed good prediction for hospital care (AUC = 0.94) although only age and unvaccinated status were found to be prognostic factors. CONCLUSIONS: We observed strong positive associations of nasopharyngeal bacterial load with severity outcomes of hospitalisation and occurrence of complications. Bacterial load and other independent variables contributed to an accurate prognostic model for hospitalisation. PMID- 26850360 TI - Serum immune biomarkers in irritable bowel syndrome. AB - BACKGROUND AND OBJECTIVES: Irritable bowel syndrome (IBS) is the most prevalent functional gastrointestinal (GI) disorder, which presents with abdominal pain and changes in the bowel habits. Although the exact cause of IBS remains uncertain, some studies have shown that the inflammation and cytokine imbalance may act as potential etiological factors. The aim of our study is to compare the serum levels of interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-alpha) in patients with IBS with the healthy controls. The other aim of this study is to evaluate possible association between above-mentioned cytokines and IBS subtypes. METHODS: Seventy-four IBS patients diagnosed based on Rome III criteria and 75 gender and age-matched healthy controls were included in this study. Cytokines were measured in the serum using enzyme-linked immunosorbent assays (ELISA). RESULTS: Patients were classified into groups of IBS with diarrhea (IBS-D): 34, IBS with constipation (IBS-C): 29, and IBS with mixed symptoms (IBS-M): 11. The serum levels of IL-6, IL-8 and TNF-alpha were significantly higher in patients with IBS as compared to controls (P<0.001). There was no difference in serum levels of cytokines based on IBS subtypes. CONCLUSIONS: Higher serum level of IL-6, IL-8 and TNF-alpha in IBS suggests an important role of cytokines as immune mediators in the pathogenesis of this functional GI disorder. To understand any association between cytokines and IBS subtypes, further investigations with larger sample sizes are desired. PMID- 26850359 TI - Demethylation of tumor necrosis factor-alpha converting enzyme predicts poor prognosis in acute-on-chronic hepatitis B liver failure. AB - BACKGROUND AND OBJECTIVE: Tumor necrosis factor-alpha converting enzyme (TACE) has been demonstrated to be involved in liver inflammation. However, the significance of TACE methylation in acute-on-chronic hepatitis B liver failure (ACHBLF) has not been demonstrated. This study aims to evaluate TACE methylation status in ACHBLF and determine its predictive value for prognosis. METHODS: Forty five patients with ACHBLF, 80 with chronic hepatitis B (CHB) and 54 healthy controls (HCs) were enrolled. The methylation status of TACE promoter was determined by methylation-specific polymerase chain reaction. The TACE mRNA expression was determined by quantitative real-time polymerase chain reaction. The plasma levels of TACE, TNF-alpha, sTNFRI, sTNFRII were measured by enzyme linked immunosorbent assay. RESULTS: TACE methylation was significantly lower in patients with ACHBLF than those with CHB (chi(2)=24.69, P<0.01) and HCs (chi(2)=35.93, P<0.01). Meanwhile, TACE methylation was significantly lower in CHB patients than HCs (chi(2)=4.03, P<0.05). TACE methylation was significantly inversely associated with its mRNA expression (r=-0.68; P<0.01). The plasma levels of TACE, TNF-alpha, sTNFRI, sTNFRII were significantly higher in patients with ACHBLF than those with CHB (P<0.05, respectively) and HCs (P<0.05, respectively). In patients with ACHBLF, significantly higher prothrombin activity, lower total bilirubin and MELD score were found in TACE methylated group than unmethylated group (P<0.05). ACHBLF patients with methylated TACE showed significantly better survival than those without (P<0.01). CONCLUSION: This study showed that demethylation of TACE promoter occurred in ACHBLF and might serve as a potential prognostic marker. PMID- 26850361 TI - Chronic hepatitis B and fatty liver: Issues in clinical management. AB - With an increasing incidence of non-alcoholic fatty livers, the existence of concomitant hepatitis B and fatty liver is becoming more common in clinical practice. In clinical practice, the concomitant existence of hepatitis B and fatty livers raises practical issues in clinical management. It becomes more difficult for the clinician to decide on the mode of treatment in the case of elevated Alanine aminotransferase (ALT) and in deciding potential causes, whether they are related to chronic hepatitis B or to non-alcoholic steatohepatitis (NASH). With evolving changes in the practice and knowledge of non-alcoholic fatty liver disease and chronic hepatitis B, clinical judgment on the predominant disease becomes essential for their coexistence. This short review is aimed at reviewing the evidence available on the frequency of the two diseases existing concomitantly, possible ways of differentiating the two, the prognosis, outcomes of treatment and a possible common pathway. PMID- 26850362 TI - Metastases of pancreatic neuroendocrine tumor to the liver as extremely rare indication for liver transplantation in children. Case report and review of the literature. AB - Neuroendocrine tumors (NET) are extremely rare in children (0.75 cases per 100,000 children and adolescents a year) and the majority of these tumors are benign or present low grade of malignancy. According to the American registry Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute, less than 2% of all neuroendocrine tumors in children occur in the pancreas, making it a rare site for these tumors. The majority of them are found in children over 10years of age, especially those with malignant potential. Treatment of NET consists of different methods: surgery, somatostatin analogues and chemotherapy. Radical surgical resection remains the standard of treatment; however, it is not always feasible because of distant metastases. The authors present a case report of pancreatic NET with multiple metastases to the liver. The patient was treated with pancreatic resection and liver transplantation for liver metastases. Prior to liver transplantation, the patient was treated with somatostatin analogues, sunitinib and chemotherapy. Management of liver metastases with liver transplantation is discussed. PMID- 26850363 TI - Rescue therapy with bismuth-containing quadruple therapy in patients infected with metronidazole-resistant Helicobacter pylori strains. AB - BACKGROUND: The emergence of H. pylori strains that are resistant to clarithromycin, metronidazole and fluoroquinolone requires the evaluation of new and effective salvage therapies. AIMS: To test the efficacy of a new formulation of a bismuth-containing quadruple therapy as a rescue therapy in patients who were infected with a H. pylori strain resistant to metronidazole, clarithromycin and fluoroquinolone or who failed multiple lines of treatment using these three antibiotics. METHODS: A total of 103 patients with confirmed H. pylori infection with a resistance profile described above were treated with Pylera((r)) (3-in-1 capsules containing bismuth subcitrate potassium 140mg, metronidazole 125mg and tetracycline 125mg) 3 capsules four times a day plus omeprazole 20mg two times a day for 10 days in a named patient program. Eradication was confirmed using a urea breath test at least 28 days after the end of treatment. Efficacy and safety were studied. RESULTS: A total of 103 patients were prospectively included from June 2010 to October 2011. The eradication rate for the intent-to-treat analysis was 83% (CI95%[75-89%]); an 87% eradication rate (CI95%[80-94%]) was found for the per-protocol analysis and 81% (CI95%[80-82%]) for the intent-to-treat analysis in patients with proven resistance to metronidazole. Nine patients discontinued treatment, all due to adverse events. Two serious adverse events (AEs) were reported (memory disorders of unknown significance). Fifty-six (54%) patients reported at least one AE. CONCLUSION: This bismuth-containing quadruple therapy achieved a remarkable eradication rate as a salvage therapy in patients infected with metronidazole-resistant H. pylori strain, despite the frequent occurrence of mild-to-moderate adverse events. PMID- 26850364 TI - Angiotensin II activates different calcium signaling pathways in adipocytes. AB - Angiotensin II (Ang II) is an important mammalian neurohormone involved in reninangiotensin system. Ang II is produced both constitutively and locally by RAS systems, including white fat adipocytes. The influence of Ang II on adipocytes is complex, affecting different systems of signal transduction from early Sa(2+) responses to cell proliferation and differentiation, triglyceride accumulation, expression of adipokine-encoding genes and adipokine secretion. It is known that white fat adipocytes express all RAS components and Ang II receptors (AT1 and AT2). The current work was carried out with the primary white adipocytes culture, and Sa(2+) signaling pathways activated by Ang II were investigated using fluorescent microscopy. Sa(2+)-oscillations and transient responses of differentiated adipocytes to Ang II were registered in cells with both small and multiple lipid inclusions. Using inhibitory analysis and selective antagonists, we now show that Ang II initiates periodic Sa(2+)-oscillations and transient responses by activating AT1 and AT2 receptors and involving branched signaling cascades: 1) Ang II -> Gq -> PLC -> IP3 -> IP3Rs -> Ca(2+) 2) Gbetagamma -> PI3Kgamma -> PKB 3) PKB -> eNOS -> NO -> PKG 4) CD38 -> cADPR -> RyRs -> Ca(2+) In these cascades, AT1 receptors play the leading role. The results of the present work open a perspective of using Ang II for correction of signal resistance of adipocytes often observed during obesity and type 2 diabetes. PMID- 26850365 TI - Transanal completion proctectomy after total colectomy and ileal pouch-anal anastomosis for ulcerative colitis: a modified single stapled technique. AB - AIM: Minimally invasive surgery has proved its efficacy for the surgical treatment of ulcerative colitis (UC). The recent evolution in single port (SP) surgery together with transanal rectal surgery could further facilitate minimally invasive surgery in UC patients. This technical note describes a technical modification for single stapled anastomoses in patients undergoing transanal completion proctectomy and ileal pouch-anal anastomosis (ta-IPAA) for UC. METHODS: A step-by-step approach of the ta-IPAA in UC is described, including pictures and a video illustration. RESULTS: We describe a ta-IPAA with SP laparoscopy at the ileostomy site. All patients underwent a total colectomy with end-ileostomy for therapy refractory UC in a first step. Colectomy was done by multiport laparoscopy in six patients, while the ileostomy site was used as single port access in five patients. In all 11 patients the stoma site was used for SP mobilization of the mesenteric root and fashioning of the J-pouch. Completion proctectomy was done using a transanal approach. A single stapled anastomosis was performed in all patients. An 18 French catheter was used to approximate the pouch to the rectal cuff. CONCLUSION: A technical modification of the single stapled anastomosis facilitates the formation of the ta-IPAA, further reducing invasiveness in UC patients. PMID- 26850366 TI - Increased recombinant protein production owing to expanded opportunities for vector integration in high chromosome number Chinese hamster ovary cells. AB - Chromosomal instability is a characteristic of Chinese hamster ovary (CHO) cells. Cultures of these cells gradually develop heterogeneity even if established from a single cell clone. We isolated cells containing different numbers of chromosomes from a CHO-DG44-based human granulocyte-macrophage colony stimulating factor (hGM-CSF)-producing cell line and found that high chromosome number cells showed higher hGM-CSF productivity. Therefore, we focused on the relationship between chromosome aneuploidy of CHO cells and high recombinant protein-producing cell lines. Distribution and stability of chromosomes were examined in CHO-DG44 cells, and two cell lines expressing different numbers of chromosomes were isolated from the original CHO-DG44 cell line to investigate the effect of aneuploid cells on recombinant protein production. Both cell lines were stably transfected with a vector that expresses immunoglobulin G3 (IgG3), and specific antibody production rates were compared. Cells containing more than 30 chromosomes had higher specific antibody production rates than those with normal chromosome number. Single cell analysis of enhanced green fluorescent protein (Egfp)-gene transfected cells revealed that increased GFP expression was relative to the number of gene integration sites rather than the difference in chromosome numbers or vector locations. Our results suggest that CHO cells with high numbers of chromosomes contain more sites for vector integration, a characteristic that could be advantageous in biopharmaceutical production. PMID- 26850367 TI - Divalent Amino-Acid-Based Amphiphilic Antioxidants: Synthesis, Self-Assembling Properties, and Biological Evaluation. AB - We report herein the synthesis of a divalent amphiphilic carrier onto which alpha phenyl-N-tert-butyl nitrone (PBN) and 6-hydroxy-2,5,7,8-tetramethylchroman-2 carboxylic acid (Trolox) antioxidants were grafted to give the divalent derivative called FATxPBN. The divalent carrier consists of two lysine amino acids as a scaffold upon which the antioxidant moieties are grafted, a perfluorinated chain that supplies hydrophobicity, and a sugar-based polar headgroup that ensures water solubility. For the sake of comparison, a divalent PBN derivative called FADiPBN was also synthesized. The self-aggregation properties of FATxPBN and FADiPBN were studied by means of surface tension, dynamic light scattering, and transmission electron microscopy methods, and showed they form small micelles (i.e., 12 and 6 nm diameter, respectively) at submillimolar concentrations (i.e., 0.01 and 0.05 mM, respectively), in agreement with partition coefficient values. The superior antioxidant properties of FATxPBN over FADiPBN and the parent compounds PBN and Trolox were demonstrated using in vitro ABTS(*+) reduction (98%) and soybean lipoxygenase inhibition (94%) assays. Finally, FATxPBN was found to significantly inhibit hyperglycemia-induced toxicity on an ex-vivo rat model, demonstrating its potency as a bioactive antioxidant against oxidative stress-induced damage. PMID- 26850368 TI - Genetic overexpressing of GPx-1 attenuates cocaine-induced renal toxicity via induction of anti-apoptotic factors. AB - The present study investigates the role of the glutathione peroxidase (GPx)-1 gene in cocaine-induced renal damage in mice. Multiple doses of cocaine increased lipid peroxidation, protein oxidation, and glutathione oxidation in the kidney of the non-transgenic mice (non-TG mice). The enzymatic activities of GPx and glutathione reductase were significantly decreased in non-TG mice, whereas superoxide dismutase was increased in the early phase of cocaine exposure. Treatment with cocaine resulted in significant decreases in expression of Bcl-2 and Bcl-xl in the kidney of non-TG mice, which resulted in significant increases in Bax and cleaved-caspase 3. Consistently, cocaine-induced tubular epithelial vacuolization and focal tubular necrosis were mainly observed in the proximal tubules in the kidneys of non-TG mice. These renal pathologic changes were much less pronounced in GPx-1 TG than in non-TG mice. These results suggest that the GPx-1 gene is a protective factor against nephrotoxicity induced by cocaine via interactive modulations between antioxidant and cell survival signaling processes. PMID- 26850370 TI - Characterization of a new strain of Aeromonas dhakensis isolated from diseased pacu fish (Piaractus mesopotamicus) in Brazil. AB - This study provides a detailed description and characterization of a strain of Aeromonas dhakensis isolated from a diseased juvenile Piaractus mesopotamicus obtained from the fish farm of the National Center for Continental Fish Research and Conservation (CEPTA/ICMBio), in the state of Sao Paul, Brazil. Biochemical tests using the VITEK 2 automated bacterial identification system identified the isolate to genus level; however, further molecular analysis of the 16S rRNA, gyrB and rpoD genes showed that the strain belonged to the species A. dhakensis. As expected, the isolated A. dhakensis strain was resistant to ampicillin and ampicillin/sulbactam, as resistance to ampicillin is a typical characteristic of the genus Aeromonas. Resistance to cefoxitin and meropenem was also observed, but the strain was susceptible to most of the tested antibiotics. The isolated strain of A. dhakensis caused acute haemorrhagic septicaemia in experimentally infected P. mesopotamicus, with a fifty per cent lethal dose of 1.14 * 105 CFU/fish. This is the first report of the occurrence of an A. dhakensis strain causing an infection in a fish species of South America, providing important epidemiologic data relating to this important pathogenic species. PMID- 26850369 TI - Spontaneous and natural cytotoxicity receptor-mediated cytotoxicity are effector functions of distinct natural killer subsets in hepatitis C virus-infected chimpanzees. AB - In humans, CD16 and CD56 are used to identify functionally distinct natural killer (NK) subsets. Due to ubiquitous CD56 expression, this marker cannot be used to distinguish between NK cell subsets in chimpanzees. Therefore, functional analysis of distinct NK subsets during hepatitis C virus (HCV) infection has never been performed in these animals. In the present study an alternative strategy was used to identify four distinct NK subsets on the basis of the expression of CD16 and CD94. The expression of activating and inhibiting surface receptors showed that these subsets resemble human NK subsets. CD107 expression was used to determine degranulation of the different subsets in naive and HCV infected chimpanzees. In HCV-infected chimpanzees increased spontaneous cytotoxicity was observed in CD94(high/dim) CD16(pos) and CD94(low) CD16(pos) subsets. By contrast, increased natural cytotoxicity receptor (NCR)- mediated degranulation after NKp30 and NKp44 triggering was demonstrated in the CD94(dim) CD16(neg) subset. Our findings suggest that spontaneous and NCR-mediated cytotoxicity are effector functions of distinct NK subsets in HCV-infected chimpanzees. PMID- 26850371 TI - Nanosized titanium dioxide resulted in the activation of TGF-beta/Smads/p38MAPK pathway in renal inflammation and fibration of mice. AB - Titanium dioxide nanoparticles (TiO2 NPs) have been demonstrated to damage the kidneys. However, whether chronic nephritis leads to renal fibration or the fibrosis is associated with the activation of TGF-beta/Smads/p38MAPK pathway caused by TiO2 NPs exposure is not well understood. Forty male mice were separately exposed to 0, 2.5, 5, or 10 mg/kg body weight TiO2 NPs for 6 months. Renal biochemical functions and levels of TGF-beta/Smads/p38MAPK pathway-related markers and extracellular matrix (ECM) expression in the kidneys were investigated. The findings showed that subchronic TiO2 NPs exposure increased levels of urinary creatisix (Cr), N-acetyl-glucosaminidase, and vanin-1, resulted in severe renal inflammation and fibration. Furthermore, TiO2 NP exposure upregulated expression of transforming growth factor-beta1 (TGF-beta1, 0.07- to 2.72-fold), Smad2 (0.42- to 1.63-fold), Smad3 (0.02- to 1.94-fold), ECM (0.15- to 2.75-fold), alpha-smooth muscle actin (0.14- to 3.06-fold), p38 mitogen-activated protein kinase (p38MAPK, 0.11- to 3.78-fold), and nuclear factor-kappaB (0.4- to 2.27-fold), and downregulated Smad7 (0.05- to 0.61-fold) expression in mouse kidney. Subchronic TiO2 NPs exposure induced changes of renal characteristics towards inflammation and fibration may be mediated via TGF-beta/Smads/p38MAPK pathway, and the uses of TiO2 NPs should be carried out cautiously, especially in humans. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1452 1461, 2016. PMID- 26850372 TI - Inhibition of NF-kappaB translocation by curcumin analogs induces G0/G1 arrest and downregulates thymidylate synthase in colorectal cancer. AB - Cell cycle progression and DNA synthesis are essential steps in cancer cell growth and resistance. Thymidylate synthase (TS) is a therapeutic target for 5FU. Curcumin is a potent inhibitor of NF-kappaB. EF31 and UBS109 are potent synthetic analogues of curcumin. We tested the hypothesis that inhibition of NF-kappaB translocation by curcumin and its analogs EF31 and UBS109 can inhibit cell cycle progression and downregulate TS levels in colorectal cancer (CRC) cell lines. Two CRC cell lines (HCT116 and HT-29) were either untreated (control) or treated with IC50 concentrations of curcumin, EF31 UBS109 led to G0/G1 cell cycle arrest. Treatment with curcumin, EF31 or UBS109 inhibited NF-kappaB, downregulated survival pathways and inhibited cell cycle progression. Arrest in the G0/G1 phase was associated with downregulation of the transcription factor E2F-1 and its target gene TS. NF-kappaB over-expression induced E2F-1 and TS protein and mRNA levels in both cell lines. EF31 and UBS109 treatment significantly decreased tumor growth in compared to untreated tumors. EF31 and UBS109 are promising agents for the prevention and treatment of CRC. PMID- 26850373 TI - Serum miRNAs as predictive and preventive biomarker for pre-clinical hepatocellular carcinoma. AB - The extremely poor prognosis of patients with symptomatic hepatocellular carcinoma (HCC) diagnosed clinically at advanced stages suggests an urgent need for biomarkers that can be used for prospective surveillance and pre-clinical screening for early presence of pre-malignant lesions and tumors. In a retrospective longitudinal phase 3 biomarker study in seven medical centers of China, time-series and 6 months interval-serum samples were collected from chronic hepatitis B virus infected (CHB) patient cohorts at the pre-malignant or pre-clinical stages (average 6 months prior to clinical diagnosis) and CHB patients that did not develop cancer, and circulating miRNAs measured. A set of serum miRNAs including miR-193a-3p, miR-369-5p, miR-672, miR-429 and let-7i* were identified in pre-clinical HCC patients and have the potential to screen for CHB patients at high risk to develop HCC 6-12 months after miRNAs measurement. These circulating miRNAs combined with the conventional screening tools using alpha fetoprotein and ultrasound, may have great promise for the prediction and prevention of HCC in high-risk populations. PMID- 26850374 TI - Animal models of colorectal cancer with liver metastasis. AB - Liver metastasis is a leading cause of death in patients with colorectal cancer. Investigating the mechanisms of liver metastasis and control of disease progression are important strategies for improving survival of these patients. Liver metastasis is a multi-step process and relevant models representing these steps are necessary to understand the mechanism of liver metastasis and establish appropriate treatments. Recently, the development of animal models for use in metastasis research has greatly increased; however, there is still a lack of models that sufficiently represent human cancer. Thus, in order to select an optimal model for of a given study, it is necessary to fully understand the characteristics of each animal model. In this review, we describe the mouse models currently used for colorectal cancer with liver metastasis, their characteristics, and their pros and cons. This may help us specify the mechanism of liver metastasis and provide evidence relevant to clinical applications. PMID- 26850375 TI - Strategies in functional proteomics: Unveiling the pathways to precision oncology. AB - Personalised strategies in cancer care are required to overcome the therapeutic challenges posed by variability between patients and disease subsets. To this end, enhanced precision tools must be developed to describe the molecular drivers of malignant proliferation. Such tools must also identify druggable targets and biomarkers in order to provide essential information regarding drug development and therapeutic outcome. Here we discuss how proteomics-based approaches provide a set of viable methodologies capable of delivering quantitative information throughout the main stages of personalised oncology and a ratiometric platform that delivers systems-wide methods for drug evaluation. PMID- 26850376 TI - Structure-activity relationship study of 4-(thiazol-5-yl)benzoic acid derivatives as potent protein kinase CK2 inhibitors. AB - Two classes of modified analogs of 4-(thiazol-5-yl)benzoic acid-type CK2 inhibitors were designed. The azabenzene analogs, pyridine- and pyridazine carboxylic acid derivatives, showed potent protein kinase CK2 inhibitory activities [IC50 (CK2alpha)=0.014-0.017MUM; IC50 (CK2alpha')=0.0046-0.010MUM]. Introduction of a 2-halo- or 2-methoxy-benzyloxy group at the 3-position of the benzoic acid moiety maintained the potent CK2 inhibitory activities [IC50 (CK2alpha)=0.014-0.016MUM; IC50 (CK2alpha')=0.0088-0.014MUM] and led to antiproliferative activities [CC50 (A549)=1.5-3.3MUM] three to six times higher than those of the parent compound. PMID- 26850377 TI - Sulfonamide inhibition studies of the beta-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae. AB - The genome of the pathogenic bacterium Vibrio cholerae encodes for three carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the alpha-, beta- and gamma-classes. VchCA, the alpha-CA from this species was investigated earlier, whereas the beta class enzyme, VchCAbeta was recently cloned, characterized kinetically and its X ray crystal structure reported by this group. Here we report an inhibition study with sulfonamides and one sulfamate of this enzyme. The best VchCAbeta inhibitors were deacetylated acetazolamide and methazolamide and hydrochlorothiazide, which showed inhibition constants of 68.2-87.0nM. Other compounds, with medium potency against VchCAbeta, (KIs in the range of 275-463nM), were sulfanilamide, metanilamide, sulthiame and saccharin whereas the clinically used agents such as acetazolamide, methazolamide, ethoxzolamide, dorzolamide, zonisamide and celecoxib were micromolar inhibitors (KIs in the range of 4.51-8.57MUM). Identification of potent and possibly selective inhibitors of VchCA and VchCAbeta over the human CA isoforms, may lead to pharmacological tools useful for understanding the physiological role(s) of this under-investigated enzymes. PMID- 26850378 TI - High Single-dose Vancomycin Loading Is Not Associated With Increased Nephrotoxicity in Emergency Department Sepsis Patients. AB - OBJECTIVE: Vancomycin loading doses are recommended; however, the risk of nephrotoxicity with these doses is unknown. The primary objective of this study was to compare nephrotoxicity in emergency department (ED) sepsis patients who received vancomycin at high doses (>20 mg/kg) versus lower doses (<=20 mg/kg). METHODS: A retrospective cohort study was performed in three academic EDs. Inclusion criteria were age >= 18 years, intravenous vancomycin order, and hospital admission. Exclusion criteria were no documented weight, hemodialysis dependent, and inadequate serum creatinine (SCr) values for the measured outcome. Analyses compared the incidence of nephrotoxicity for patients who received vancomycin at high dose (>20 mg/kg) versus low dose (<=20 mg/kg). RESULTS: A total of 2,131 consecutive patients prescribed vancomycin over 6 months were identified. Of these, 1,330 patients had three SCr values assessed for the primary outcome. High-dose initial vancomycin was associated with a significantly lower rate of nephrotoxicity (5.8% vs. 11.1%). After age, sex, and initial SCr were adjusted for, the risk of high-dose vancomycin compared to low-dose was decreased for the development of nephrotoxicity (relative risk = 0.60; 95% confidence interval = 0.44 to 0.82). CONCLUSION: Initial dosing of vancomycin > 20 mg/kg was not associated with an increased rate of nephrotoxicity compared with lower doses. Findings from this study support compliance with initial weight based vancomycin loading doses. PMID- 26850379 TI - Feedback from each retinal neuron population drives expression of subsequent fate determinant genes without influencing the cell cycle exit timing. AB - During neurogenesis, progenitors balance proliferation and cell cycle exit together with expression of fate determinant genes to ensure that the correct number of each of these neuron types is generated. Although intrinsic gene expression acting cell autonomously within each progenitor drives these processes, the final number of neurons generated is also influenced by extrinsic cues, representing a potential avenue to direct neurogenesis in developmental disorders or regenerative settings without the requirement to change intrinsic gene expression. Thus, it is important to understand which of these stages of neurogenesis are amenable to such extrinsic influences. Additionally, all types of neurons are specified in a highly conserved histogenic order, although its significance is unknown. This study makes use of conserved patterns of neurogenesis in the relatively simple yet highly organized zebrafish retina model, in which such histogenic birth order is well characterized. We directly visualize and quantify birth dates and cell fate determinant expression in WT vs. environments lacking different neuronal populations. This study shows that extrinsic feedback from developing retinal neurons is important for the temporal expression of intrinsic fate determinants but not for the timing of birth dates. We found no changes in cell cycle exit timing but did find a significant delay in the expression of genes driving the generation only of later- but not earlier born cells, suggesting that the robustness of this process depends on continuous feedback from earlier-formed cell types. Thus, extrinsic cues selectively influence cell fate determinant progression, which may explain the function of the retinal histogenic order observed. J. Comp. Neurol. 524:2553-2566, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26850381 TI - Model for the allosteric regulation of the Na+/Ca2+ exchanger NCX. AB - The Na(+) /Ca(2+) exchanger provides a major Ca(2+) extrusion pathway in excitable cells and plays a key role in the control of intracellular Ca(2+) concentrations. In Canis familiaris, Na(+) /Ca(2+) exchanger (NCX) activity is regulated by the binding of Ca(2+) to two cytosolic Ca(2+) -binding domains, CBD1 and CBD2, such that Ca(2+) -binding activates the exchanger. Despite its physiological importance, little is known about the exchanger's global structure, and the mechanism of allosteric Ca(2+) -regulation remains unclear. It was found previously that for NCX in the absence of Ca(2+) the two domains CBD1 and CBD2 of the cytosolic loop are flexibly linked, while after Ca(2+) -binding they adopt a rigid arrangement that is slightly tilted. A realistic model for the mechanism of the exchanger's allosteric regulation should not only address this property, but also it should explain the distinctive behavior of Drosophila melanogaster's sodium/calcium exchanger, CALX, for which Ca(2+) -binding to CBD1 inhibits Ca(2+) exchange. Here, NMR spin relaxation and residual dipolar couplings were used to show that Ca(2+) modulates CBD1 and CBD2 interdomain flexibility of CALX in an analogous way as for NCX. A mechanistic model for the allosteric Ca(2+) regulation of the Na(+) /Ca(2+) exchanger is proposed. In this model, the intracellular loop acts as an entropic spring whose strength is modulated by Ca(2+) -binding to CBD1 controlling ion transport across the plasma membrane. PMID- 26850382 TI - [Achievement of HIV/AIDS program in the past 30 years and challenges in China]. PMID- 26850380 TI - White Paper on P4 Concepts for Pediatric Imaging. AB - Over the past decade, innovations in the field of pediatric imaging have been based largely on single-center and retrospective studies, which provided limited advances for the benefit of pediatric patients. To identify opportunities for potential "quantum-leap" progress in the field of pediatric imaging, the ACR Pediatric Imaging Research (PIR) Committee has identified high-impact research directions related to the P4 concept of predictive, preventive, personalized, and participatory diagnosis and intervention. Input from 237 members of the Society for Pediatric Radiology was clustered around 10 priority areas, which are discussed in this article. Needs within each priority area have been analyzed in detail by ACR-PIR experts on these topics. By facilitating work in these priority areas, we hope to revolutionize the care of children by shifting our efforts from unilateral reaction to clinical symptoms, to interactive maintenance of child health. PMID- 26850383 TI - [Characteristics of HIV transmission through heterosexual contact in China, 2008 2014]. AB - OBJECTIVE: To understand the epidemiological characteristics and changing patterns of HIV transmission through heterosexual contact since 2008, and to project the influences of heterosexual transmission mode on the HIV epidemic in China. METHODS: Demographic data and history of exposure in newly identified HIV/AIDS cases aged 15 years or older, through heterosexual transmission mode from 2008 to 2014, were collected and analyzed. RESULTS: The number of HIV/AIDS cases caused by heterosexual transmission increased from 23 402 in 2008, to 68 671 in 2014. The proportion of heterosexual transmission mode increased from 8.7% in 2008 to 66.4% in 2014. Among these cases, the proportion of males increased from 55.3% in 2008 to 68.2% in 2014. Among those who reported acquiring HIV through heterosexual contact, the proportion of cases through extramarital sexual acts out of all the newly report ones, increased from 78.2% in 2008 to 88.2% in 2014. This mode of infection accounted for 85.2% in the age 15 to 49 years group, comparing to 84.2% in the age group of 50 years old or above. The proportion of reported HIV infections through extramarital sexual acts appeared 93.8% on males while 69.0% on females, with statistically significant difference (chi(2)=36 000.000, P<0.001). CONCLUSION: As the predominant factor of HIV/AIDS epidemic, currently in China, heterosexual transmission showed diversities in different sub epidemic areas, gender or age groups. Tailored strategies were urgently needed for health education and highrisk behavioral intervention, according to the local epidemic driven factors, respectively. PMID- 26850384 TI - [Implementation of intervention programs on AIDS-related sexual transmission in China]. AB - OBJECTIVE: To analyze the implementation of intervention programs targeted on AIDS high risk sexual transmission groups since 2008, when the relative prevention and control information systems on HIV/AIDS were developed. METHODS: Data from both aggregated interventions and sentinel surveillance programs from 2008 to the end of 2014 were used. Descriptive statistics were performed to analyze the trends of implementation on high risk groups including men who have sex with men, female sex workers (FSW) and migrant workers. RESULTS: From 2008 to 2012, the monthly average numbers receiving intervention programs and the average monthly coverage rate on intervention for MSM, increased from 49 000 to 252 000, and from 8.6% to 78.5% respectively. The FSW related indicators increased from 329 000 to 625 000, and from 30.9% to 87.0% respectively. Above indexes on the two populations had dropped slightly in 2013 and 2014. Sentinel surveillance data showed that knowledge and behavior indicators observed from the MSM and FSW populations increased annually. The coverage of intervention programs on migrant workers increased from 4.7% to almost 10.0%, but the surveillance data on migrant men showed that the knowledge and behavior indicators were still lower than the other high-risk groups. CONCLUSION: Intervention related to sexual transmission on HIV/AIDS among high-risk populations were effectively implemented, with some achievements seen. However, as sexual contact currently became the main route of AIDS epidemic, new challenges called for serious attention. PMID- 26850385 TI - [The improvement of follow-up services for people living with HIV/AIDS in China from 2008 to 2014]. AB - OBJECTIVE: This article endeavors to describe the key indicators of follow-up services for people living with HIV/AIDS (PLWHA) in China from 2008 to 2014. METHODS: All data were extracted from the National Comprehensive HIV/AIDS database and cleaned, based on three key indicators (proportion of follow-up of PLWHA, CD(4) testing of PLWHA and HIV antibody testing of PLWHA' s spouse or partner) defined and developed by the National Center for AIDS/STD Control and Prevention for case management. Both key indicators were analyzed and comparisons were performed annually from 2008 through 2014. RESULTS: The proportion of follow up of PLWHA increased from 55.7% to 94.7% and the proportion of PLWHA' s CD(4) testing increased from 48.4% to 88.3%. The proportion of HIV antibody testing among PLWHA' s spouse or partner increased from 48.3% to 91.1%, during this period. The three indicators showed an yearly significant increase (intervention: chi(2)=180 466.733, P<0.01 ;CD(4): chi(2)=35 982.374, P<0.01; partner testing: chi(2)=43 108.270, P<0.01). PLWHA with a history of injecting drug use (IDU) , incarceration, as well as unknown infection route appeared significant lower proportion through the follow-up services. CONCLUSION: Both follow-up services and the chosen key indicators set for PLWHA showed dramatic improvement but called for further reinforcement. Information that had been collected from cases when initial diagnosis was made, appeared vital during the follow-up services. PMID- 26850386 TI - [Progress on China' s national free antiretroviral therapy strategy in 2002 2014]. AB - OBJECTIVE: To analyze the progress and characteristics of China' s "Free AIDS treatment strategy" since the implementation of the national "four free and one care" policy against AIDS 12 years ago. METHODS: Retrospective cohort study and cross-sectional analysis had been conducted in this study. 368 449 cases that had received the ' free antiviral therapy' from 2002 to 2014 were selected from the National Treatment Database. Data from the baseline (initial time of ART, CD(4) cell count, and antiretroviral regimen) and from the follow-up program (dates and status of follow-up, CD(4) cell counts) were gathered and analysed by SAS 9.3. RESULTS: The number of cases that having received new treatment was increasing year by year, accounting for 75.4% of all the cases identified from 2010 to 2014. Constituent ratios of patients with baseline CD(4) cell count <200 cells/ul and clinical diagnosis of AIDS were decreasing from 81.0% in 2006 to 39.7 % in 2014. Status on drug optimization showed that: 3TC replaced DDI, EFV replaced NVP and TDF replaced D4T, making the utilization rates as 99.5%, 75.7%, and 60.6%, respectively, by 2014. Regions that were covered by the treatment accounted for 75.4% of all the counties/districts involved. The previous CDC-led AIDS treatment program and mode of management had been transferred to the hospital-based model. Proportion on the twice-CD(4)-testing model had been 75.2% since 2010, with the rate of virological detection increased from 70.8% in 2010 to 87.4% in 2014 and the virological unsuccessful testing rate decreased from 17.6% in 2010 to 11.8% in 2014. Among all the patients, the 1, 5 and 10 year survival rates appeared as 92.2%, 80.5% and 69.6%, respectively. For patients with baseline CD(4) cell counts as <50 cells/ul or >350 cells/ul, the corresponding survival rates showed as 81.6% , 69.9% , 60.9% and 97.9%, 89.8% , 81.0%, respectively. CONCLUSION: China' s HIV/AIDS free antiretroviral therapy program appeared as a national treatment cohort which involved large number of participants, with new patients joining in, annually. Criterion on drug optimization and treatment were consistently following the recommendation and guidelines set by WHO. Management program on treatment had gradually turned to hospital-based, with follow-up and laboratory testing programs guaranteed, ended up with satisfactory treatment effects. PMID- 26850387 TI - [Multi-center cross-sectional study on type-specific human papillomavirus infection among Chinese women]. AB - OBJECTIVE: To study the type-specific prevalence of human papillomavirus (HPV) infection among women in China and to provide evidence for primary prevention and screening of cervical cancer programs. METHODS: From May, 2004 to April, 2007, a population-based multicenter cross-sectional study was conducted by the Cancer Hospital, Chinese Academy of Medical Sciences. Women aged 17-59 years from 4 urban areas and 4 rural areas, were screened, under both liquid based cytological and HPV tests for cervical cancer. Specimens of cervical cell were used for genotyping with Linear Array or enzyme-linked immunesorbent assay. Women showed positive in primary screening were referred to exams for further colposcopy and/or histo-pathological detections. RESULTS: A total of 6723 women were included in the data analysis. The overall prevalence of HPV infection was 15.5%. Two age-specific peaks of prevalence of HPV infection were detected among the different age groups. The first peak occurred in 17-24 year-old women in both rural areas and urban areas, while the second one occurred in 40-44 year-old women in urban areas and in 45-49 year-old women in rural areas. The prevalence of HPV infection increased with the severity of diagnosed cervical intraepithelial lesions by cytological or histo-pathological test (chi(2)=62.857, 22.113, P<0.001). HPV16 (3.2%) was seen the most common high risk HPV type, followed by HPV58 (1.8%) , HPV52 (1.5%) , HPV18 (1.0%) and HPV33 (1.0%) respectively. Other common types would include HPV66 (0.64%) , HPV42 (0.58%) and HPV53 (0.46%). The prevalence of HPV16 infection in rural women was significantly higher than that in urban women (chi(2)=4.696, P< 0.05). CONCLUSION: Prevalence of HPV infection in Chinese women seemed to be high and with two age-specific peaks. HPV16 appeared the most commonly seen type in women with cervical lesions. HPV58 and 18 were the predominant types. Type-specific distribution of HPV infection should be taken into consideration in the development of comprehensive cervical cancer prevention strategies in China. PMID- 26850388 TI - [Association between waist circumference and the prevalence/control of hypertension by gender and different body mass index classification in an urban elderly population]. AB - OBJECTIVE: The aim of the present study was to evaluate the association between waist circumference and the prevalence/control of hypertension in an urban elderly population. METHODS: From September 2009 to June 2010, a population-based cross-sectional study was conducted in Wanshoulu area of Beijing, China. RESULTS: A total of 2 035 elderly (828 male, 1 207 females) participants aged >=60 years from a community were included in this study for data analysis. We found that the increased waist circumference could significantly increase the risk of prevalence and poor control of hypertension, with the adjusted odds ratios (95% CI) as 1.04 (1.01-1.08) and 0.96 (0.92-1.00) , respectively. Among those identified pure central obesity females (64.7%) , the prevalence of hypertension was significantly higher than those females with normal body mass index (BMI) or with normal waist circumference (52.2%). The adjusted odds ratio (95%CI) between the above said groups appeared as 1.58 (1.07-2.32). The control rate of hypertension among females (32.9%) with pure central obesity, was lower than that of the females with normal BMI and waist circumference (43.5%) , with an adjusted odds ratio (95%CI) as 0.62 (0.37-1.04, P=0.071). CONCLUSION: There appeared significant association between people with pure central obesity and the increased risk of prevalence or with poor control of hypertension. More attention should be paid to both the prevalence and control of hypertension programs among females with pure central obesity. PMID- 26850389 TI - [Association between social support and outcomes as successful smoking cessation in males from the rural areas]. AB - OBJECTIVE: To examine the association between social support and successful smoking cessation outcomes in males from rural areas. METHODS: A community-based case-control study was conducted with 642 adult male cases who appeared to be successful spontaneous smoking quitters as cases, together with other 700 adult males who failed quitting smoking to serve, as controls. Social Support Rating Scale (SSRS) was used to assess the individual social support. Multiple linear method was used to evaluate the relationship between social support and the outcome of successful cessation in smoking. RESULTS: After adjusting the potential confounders as age, education, marital status, profession, age of initial smoking and number of pack-years on smoking, the adjusted mean of subjective social support in successful quitters was significant lower than that in the failed ones (P<0.001). The differences of adjusted means between objective social support and its utility were not statistically different in the two groups among the population who recognized that cigarettes should always be provided when people interact with each other (P=0.124; P=0.763). However, the adjusted means of social support and the related three dimensions did not show significant differences in the two groups among the population in disapproval of the above said social norms (P>0.05). CONCLUSION: Data from our research indicated that social support would negatively affect the successful spontaneous cessation of smoking among people under unhealthy smoking culture. PMID- 26850390 TI - [Epidemiological investigation on autism spectrum disorders among preschool children in Shanghai]. AB - OBJECTIVE: To investigate the prevalence of autism spectrum disorders (ASD) of children aged 4-6 years in public kindergartens in Shanghai. METHODS: Songjiang district and Xuhui district were selected randomly as the representative sample. By means of "Clancy Autism Behavior Scale", "Social Communication Questionnaire" and "high-functioning Autism Spectrum Screening Questionnaire", all of the 33 public kindergartens in chosen area, which contained 10 385 children aged 4-6 years, were surveyed. Those who were screened as suspected cases would be further diagnosed by "Autism Diagnostic Interview-Revised" and "Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition". RESULTS: Among 9 665 valid questionnaires, 9 children were diagnosed with ASD. The ratio of male to female was 8:1, the point prevalence rate was 0.930/00. The results of ADI-R corresponded with that of DSM-5. There were two children who never had medical records. For others, "language" problem was the most likely reason for their parents to seek medical help, while "deficits in social communication" was the main symptom of patients. CONCLUSION: The prevalence of ASD was lower than those recorded in literature, home and abroad which might be related to some patients not going to public kindergartens. PMID- 26850391 TI - [Pre- and post-iodine nutritional status among the population related to the practice of new standard on edible iodized salt, in Yunnan province]. AB - OBJECTIVE: In order to understand the iodine nutritional status, after the salt iodine content was showed a reduction in 2012 and to evaluate the current situation after the new standards was brought into force to the general population in an experimental community of Yunnan province. METHODS: Randomly sampled urine and salt were collected, to test the iodine concentration in the study-site. Pre-and post-levels of the iodized salt under the provision of the new standards, were identified. RESULTS: of this study were gathered upon 3 weeks or 3 months, respectively. Results Data from the three randomly chosen study sites showed that the urine iodine concentration in the general populations was reducing gradually. In the general population, medians of Urine Iodine (MUI) were 279.71 ug/L, 239.64 ug/L and 226.26 ug/L, respectively. Proportion of the urine iodine value for 100-199 ug/L increased but >=300 ug/L decreased, after the new standard was put into practice. Both homogeneity and stability of the new standard on iodized salt seemed to be good. CONCLUSION: Iodine nutrition in general population appeared reasonable under the use of newly set salt-iodine standards in general population living in Yunnan province. PMID- 26850392 TI - [Persistence of immune memory to hepatitis B vaccine among infants with normal or high antibody response to primary vaccination: a five-year following-up study]. AB - OBJECTIVE: To examine the immune memory status to hepatitis B vaccine among infants with normal or high antibody response to primary vaccination, 5 years after the primary vaccination and the risk factors associated with the immune memory. METHODS: Titers of the antibody against hepatitis B surface antigen (anti HBs) were detected, five years after the primary vaccination among children who appeared normal or high response to hepatitis B primary vaccination in infancy. Those whose anti-HBs titers were low than protective level (10 mIU/ml) were given a challenge dose of hepatitis B vaccine and titers of anti-HBs were detected 14 days after the challenge. Positive rate and geometric mean titer (GMT) of anti HBs were calculated. Level of the anti-HBs titers after primary vaccination, at following-up and after the challenge periods were divided into different levels, respectively. Risk factors associated with the levels of anti-HBs titer after the challenge were examined by univariate analysis that and multivariable analysis. RESULTS: Anti-HBs waned to the level below protective standard among 37.98% of the children with normal or high antibody response to hepatitis B primary vaccination; among those children whose anti-HBs were below the protection standard. The seroconversion rate and GMT of anti-HBs after the challenge dose were 98.95% (757/765) and 2 811.69 mIU/ml [95% Confidence Interval (CI) :2 513.55 3 145.19 mIU/ml] , respectively. Titers and levels of anti-HBs after the challenge, appeared an increase with anti-HBs after primary vaccination and the anti-HBs in the following-up (F=5.46, 10.23 respectively; P<0.000 1 for both) periods. Results from the multivariable analysis showed that gender, premature birth and birth weight were factors insignificantly associated with the anti-HBs titers after the dose of challenge, while the anti-HBs levels were independently associated with the levels of anti-HBs titer after the challenge [OR = 1.001 (95%CI: 1.000-1.002) , P<0.001; OR=1.28 (95%CI: 1.81-1.39) , P<0.001]at the following-up periods. CONCLUSIONS: Strong immune memory could be found among those children with normal or high responses to hepatitis B vaccination, 5 years after the primary vaccination. The intensity of immune memory might be associated with the anti-HBs titer after primary vaccination as well as the anti-HBs titers before the challenge dose was given. PMID- 26850393 TI - [Willingness on accepting the short-message-service and factors related to HIV/STD testing among male STD clinic clients]. AB - OBJECTIVE: To understand the willingness on acceptance of a short-messageservice (SMS) program provided for HIV/STD testing and the related factors, among male clients at the STD clinics in China. METHODS: Convenience sampling method was used to select study subjects at a STD clinic in Wuxi, Jiangsu province. A questionnaire survey was conducted among the subjects to collect the information on socio-demographic characteristics and willingness of acceptance to the SMS. RESULTS: A total of 368 SMS subjects were surveyed, in which 75.5% expressed the willingness of acceptance, while 57.2% and 38.1% of them wanted to receive the short message every 3 months or 6 months, respectively. 53.8% of the respondents showed their willingness to share the news with their sexual partners about SMS and 44.8% of them would do the same to their friends. Data from the Multivariate logistic regression analysis showed that those who had received senior high school or above education (aOR=3.632, 95%CI: 1.939-6.715) , having homosexual behavior (aOR = 1.973, 95%CI: 1.234-8.358) or those having received AIDS related intervention service in the past year (aOR=9.416, 95%CI: 4.822-18.309) were more likely to accept the SMS. CONCLUSION: SMS seemed to be acceptable among the male STD clinic clients in Wuxi, suggesting that it is feasible to conduct the SMS as a strategy to improve the HIV/STDs testing program at the STD clinics in the future. Promotion of SMS should be strengthened and the provision of general AIDS intervention service at the STD clinics should be established in order to make more STD clinic clients understand this SMS. PMID- 26850394 TI - [HIV incidence and factor related to lost-to-follow-up among men who have sex with men in Harbin, Heilongjiang]. AB - OBJECTIVE: To estimate the incidence of human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) and its related factors in Harbin, Heilongjiang province. METHODS: A total of 661 MSM were recruited at baseline study from April to June 2013, and followed at 6 months, 12 months, and 18 months periods, respectively. Face to face questionnaire interviews were conducted and venous blood was collected for HIV testing among these people. Univariate logistic regression model was used to identify the factors associated with lost-to-follow-up in the cohort. RESULTS: At the end of 18-month follow-up period, the HIV incidence density in the cohort was 4.23/100 person year (95%CI: 2.91/100 person year-5.93/100 person year) , with the follow-up rate of loss as 15.4%. Factors as failed to receiving the intervention programs, being at older age, with higher education level and receiving no HIV testing in this MSM community, were related to the loss of follow-up. CONCLUSION: The HIV incidence rate was high among the MSM in Harbin. MSM community based cohort study could improve the efficiency on the study for the problems of follow-up. PMID- 26850395 TI - [Association between type 2 diabetes mellitus and risk of cancers: a cohort study]. AB - OBJECTIVE: To understand the association between type 2 diabetes and the risk of cancers. METHODS: Data related to type 2 diabetes mellitus (T2DM) cases and cancer cases were collected from Zhejiang Chronic Disease Surveillance Information and Management System (CDSIMS) , between January 1, 2007 and December 31, 2013. Cumulative incidence and relative risk (RR) with 95% confidence interval (CI) were calculated. RESULTS: From 2007 to 2013, a total of 327 268 T2DM and 7 435 cancer cases were respectively reported and 778 439 person-years completed the followed-up program. Among the T2DM patients, incidence of cancers was 955.12 per 100 000, with standardized incidence as 458.05 per 100 000. Compared with people without T2DM, the risk of cancer incidence increased in T2DM patients (RR=1.68, 95%CI: 1.68-1.70). Risk appeared the highest in 20-39 year age group but decreased when the increase of age. In addition, the increased risk was still significant in T2DM patients aged >=60 years (RR=1.21, 95%CI: 1.18-1.25). CONCLUSION: Results from the study suggested that T2DM was associated with the increased risk of cancers, statistically. PMID- 26850396 TI - [Injury mortality in China, from 1990 to 2010]. AB - OBJECTIVE: To analyze the changing pattern of injury mortality from 1990 to 2010 in China. METHODS: Data related to injury mortality between 1990 and 2010 from the estimates of the Global Burden of Disease 2010 were analyzed by sex, age, causes and risk factors, under the linear regression model. RESULTS: The rates on mortality of injuries showed a significant decline between 1990 and 2010, especially in women and in children aged 0-4 years. In 2010, there were around 796 thousand people died from all kinds of injuries, with an age-standardized mortality as 57/100 000 population. Rates on injury mortality were higher in men and in people aged 70 years or over, than in women or in younger age groups. In contrast to the substantial increase on mortality rate caused by road injury, all the other causes induced mortalities showed distinct decrease. In 2010, injuries accounted for 9.6 percent of the total number of deaths in China, which exceeded the number of deaths caused by communicable, maternal, neonatal diseases or nutritional disorders. The leading causes of injury mortality were road traffic injury, self-hurt, drowning and falls in 2010. In addition, major risk factors that causing injury mortality reduced during the study period, and the top three risk factors showed as occupational-related, alcohol use, and low bone mineral density (osteoporosis). CONCLUSION: Despite the fact that rates on injury-related mortality were decreasing, injury remained a critical public health problem in China. PMID- 26850397 TI - [Study on malnutrition status among Wa ethnicity children and adolescents in Lingcang prefecture, Yunnan province]. AB - OBJECTIVE: To analyze the malnutrition status among children and adolescents of Wa ethnicity in Lincang prefecture, Yunnan province from 2005 to 2014, and to provide evidence for the improvement of the situation. METHODS: From 2005 to 2014, children and adolescents aged 7 to 18, from 19 primary and secondary schools in Cangyuan county of Lincang prefecture, Yunnan province, were chosen, using the multistage-stratified-random cluster sampling method, to receive physic examination. WHO-2006 standard was used. Situation related to the rate of growth retardation and malnutrition among students was analyzed, from 2005 to 2014. Data was from the National Student Physical Health Research Project. From 2000 to 2014, trends on nutrition development among these students were also studied. RESULTS: The rates related to growth retardation among 7-18 years-old Wa boys in 2005, 2010 and 2014 were 45.61%, 52.36% and 35.85%, with the rates of thinness as 1.44%, 0.76% and 1.36% , respectively. Rates on malnutrition were 52.35% , 56.01% and 41.13% , respectively. Rates related to growth retardation among 7-18 years old Wa girls were 42.03%, 47.41% and 33.06%, respectively, with rates of thinness as 0.91%, 0.68% and 0.83%, respectively. The rates on malnutrition were 46.13%, 49.77% and 35.56%, respectively. From year 2005 to 2014, spurt on height growth of boys and girls were among the 13-14 years-old and 9-10 years-old, respectively. Girls were 4 years earlier, entering the sudden increase in the peak age than boys. Sex difference on height among the 18 years-old Wa youngsters were 11.99, 9.34 and 11.38 cm in 2005, 2010 and 2014, respectively. CONCLUSION: Malnutrition status of retardation on growth among Wa children and adolescents remained quite serious. PMID- 26850398 TI - [Application of nonlinear autoregressive neural network in predicting incidence tendency of hemorrhagic fever with renal syndrome]. AB - OBJECTIVE: To explore the prospect of nonlinear autoregressive neural network in fitting and predicting the incidence tendency of hemorrhagic fever with renal syndrome (HFRS) , in the mainland of China. METHODS: Monthly reported case series of HFRS in China from 2004 to 2013 were used to build both ARIMA and NAR neural network models, in order to predict the monthly incidence of HFRS in China in 2014. Fitness and prediction on the effects of these two models were compared. RESULTS: For the Fitting dataset, MAE, RMSE and MAPE of the ARIMA model were 148.058, 272.077 and 12.678% respectively, while the MAE, RMSE and MAPE of NAR neural network appeared as 119.436, 186.671 and 11.778% respectively. For the Predicting dataset, MAE, RMSE and MAPE of the ARIMA model appeared as 189.088, 221.133 and 21.296%, while the MAE, RMSE and MAPE of the NAR neural network as 119.733, 151.329 and 11.431% respectively. CONCLUSION: The NAR neural network showed better effects in fitting and predicting the incidence tendency of HFRS than using the traditional ARIMA model, in China. NAR neural network seemed to have strong application value in the prevention and control of HFRS. PMID- 26850399 TI - [emm types of mutation in scarlet-fever-related group A streptococcal, among children in Beijing, 2011-2014]. AB - OBJECTIVE: To understand the distribution of emm gene types related to group A streptococcus-caused scarlet fever among children in Beijing and to analyze the relationship between the mutation of the emm types and scarlet fever. METHODS: Nasopharyngeal swab samples were collected from the scarlet fever cases diagnosed in 36 hospitals in Beijing to isolate the GAS strains from May to July, betgween 2011 and 2014. Genotyping of emm gene was performed with PCR and N-terminal gene fragments of M protein were sequenced. Data of all the scarlet fever cases in Beijing that reported through the National Notifiable Infectious Disease Surveillance System (NNIDSS) , were gathered and analyzed. RESULTS: Among the collected 2 161 nasopharyngeal swabs, 762 GAS strains were identified (35.3%). In addition, 7 emm types were detected, in which emm12 accounted for 69.4% (529/762) , emm1 accounted for 29.8% (227/762) , and other five types (emm 11, 22, 75, 89, and 128) accounted for 0.8% (6/762) , respctively. Compared with the emm types detected between 2011 and 2014, emm12, emm1 and other types accounted for 82.2% (295/359) , 16.7% (60/359) and 1.1% (4/359, including emm11, 22 and 89) in 2011 respectively.emm12, emm1 and emm75 accounted for 77.3% (123/163) , 23.9% (39/163) and 0.6% (1/163) respectively in 2012. emm12 and emm1 accounted for 50.7% (38/75) and 49.3% (37/75) in 2013 while emm12, emm1 and emm128 accounted for 44.2% (73/165) , 55.2% (91/165) and 0.6% (1/165) respectively in 2014. The differences of the constitution of emm types from 2011 to 2014 appeared statistically significant (P<0.001). In 2011 and 2012, major type appeared as emm12, but in 2014, emm1 became predominant. A total of 6 152 cases were reported in 2011, while 2 908, 2 048 and 3 918 cases were reported in 2012, 2013 and 2014 respectively. Age specific differences were noticed in the distribution of emm types GAS strains in 2011, with the number of emm12 strains detected higher in 1 5 year olds than in age group > 5 years (P<0.05). There were area specific differences in distribution of emm types of GAS strains seen in 2011 and 2013. In 2011, the number of emm1 strains detected in urban area was higher than in suburb area (P<0.05). However, in 2013, the number of emm1 strains detected in suburb area was seen higher than in urban area (P< 0.05). CONCLUSION: GAS with emm12 and GAS emm1 appeared interchangeably predominant in Beijing from 2011 to 2014. Changes in predominant emm types seemed also related to the trends of incidence rates on scarlet fever. PMID- 26850401 TI - [Influencing factors on AIDS-related deaths in Guangzhou 1991-2013]. AB - OBJECTIVE: To analyze the influencing factors on AIDS-related deaths among HIV/AIDS patients in Guangzhou, Guangdong province. METHODS: A retrospective cohort was formed, based on available data of HIV/AIDS patients between 1991 and 2013 in Guangzhou, that were gathered from the Chinese AIDS Prevention and Control Information System. Cox proportional hazard model was used to identify the influencing factors for AIDS-related deaths. RESULTS: Data showed that factors as: existence of full-bloom AIDS when HIV infection was diagnosed (HR =2.717, 95%CI: 2.039-3.621) , diagnose of AIDS was made in the hospitals (HR=1.516, 95%CI: 1.159-1.981) , never received no CD(4) count testing (HR=4.866, 95%CI: 3.674-6.444) , no drugs were provided to those who met the criteria for treatment (HR=12.213, 95%CI: 8.467-17.616) , and patients at aged >=40 years when HIV infection was diagnosed etc., were related to the risk for AIDS deaths. The risk of AIDS-related death was also high in those who did not meet the treatment criteria or receiving no treatment, when compared to those who had received the antiviral treatment (HR=1.936, 95%CI: 1.145-3.272). CONCLUSION: Factors as: earlier diagnosis of HIV/AIDS cases, provision of CD(4) count testing and antiviral treatment to more cases etc, could decrease the risk for AIDS-related deaths and improve the survival rate on HIV/AIDS cases. PMID- 26850400 TI - [Efficacy of antiviral therapy on prevention of HIV transmission among sero discordant couples in Guangxi Zhuang autonomous region]. AB - OBJECTIVE: To understand the efficacy of antiviral therapy on prevention of HIV transmission and to assess the feasibility of treatment-as-prevention strategy in public health practice, among sero-discordant couples in Guangxi Zhuang autonomous region (Guangxi). METHODS: Data was gathered through the AIDS prevention and control information system in Guangxi from January 1, 2008 to December 31, 2014, on HIV sero-discordant couples. Time-dependent Cox Model was used to analyze the efficacy of antiviral treatment. RESULTS: A total of 7 694 sero-discordant couples were followed and 394 appeared positive from those negative spouses. The overall HIV positive seroconversion rate was 2.5 (2.2-2.7) /100 person-year. The HIV positive sero-conversion rates were 4.3 (3.7-4.8) /100 person-year in the untreated cohort and 1.6 (1.4-1.9) per 100 person-year in the treated cohort. Rate of HIV transmission declined by 51% in the treated cohort (HR=0.49, 95%CI: 0.40-0.60) but appeared as 45% (AHR=0.55, 95%CI:0.43-0.69) after adjusting for factors as sex, age, education, marital status, occupation, transmission route and baseline CD4(+)T lymphocyte cell count. The rate of reduction in transmission was significant among couples in which the HIV-positive spouses showing the following features as: aged >=25 years, married, farmers, with educational level of junior high school or below, baseline CD4(+)T lymphocyte cell count <500 cells/mm(3) and infection was through heterosexual intercourse. CONCLUSION: Antiviral therapy as a prevention strategy among sero discordant couples seemed feasible and effective in Guangxi. Expansion of the coverage on antiviral therapy would reduce the spread of HIV in married couples. PMID- 26850402 TI - [Genetic diversity of Francisella tularensis subsp. holarctica in China]. AB - OBJECTIVE: To explore the genetic relationship between the Chinese and the foreign species of Francisella tularensis. METHODS: Based on our own findings and from the literature, 17 SNP, 4 INDEL, and 12 VNTR were selected for phylogenetic analysis on 39 strains of F.tularensis, including 10 strains of Chinese F. tularensis and 29 strains of foreign F. tularensis that had been sequenced and published. SNP-INDEL and MLVA were used for the separation and combination. RESULTS: Data from the combined analysis indicated that 3 strains of Chinese F. tularensis with Japanese FSC022 were assigned to B5; 3 strains, with Swedish FSC200 to B1; 3 strains with American OSU18 to B2 and 1 strain with French FTNF002-00, German F92, and American OR96246 to B4, respectively. 10 strains of Chinese F. tularensis were assigned to 4 clades and the result demonstrated a wide diversity of F. tularensis subsp.holarctica in China. CONCLUSION: A set of simple and robust typing tools for F. tularensis subsp.holarctica were established in this study. Based on the results, F. tularensis subsp.holarctica might have had its origins in Asia. PMID- 26850403 TI - [Study on the interaction between matrix metalloproteinases gene polymorphism and central obesity in nonalcoholic fatty liver disease]. AB - OBJECTIVE: To study whether matrix metalloproteinases-9 (MMP) -1562C/T (rs3918242) and MMP-2-1306C/T (rs243865) were associated with the susceptibility on nonalcoholic fatty liver disease (NAFLD) and the interactions between the two factors and central obesity. METHODS: Genotypes of 545 patients and 636 subjects with NAFLD under control were examined by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Unconditional logistic regression (ULR) was performed to assess the NAFLD risk. The gene-environment interactions on the risk of NAFLD were explored by generalized multifactor dimensionality reduction (GMDR) and ULR methods. RESULTS: Results from the case control analysis indicated that there was an increased risk of developing NAFLD for MMP-9 rs3918242 (TT/CT) genotype carriers, when compared with the non carriers (CC) , with OR=1.67, 95%CI: 1.32-2.12, P=0.001; Adjusted OR=1.65, 95% CI: 1.31-2.01 (P=0.008). However, risk reduction of NAFLD was found when MMP-2 rs243865 (TT/CT) genotype carriers compared with the non-carriers (CC) , with OR=0.68, 95% CI: 0.53-0.86, P=0.001; with adjusted OR=0.66, 95% CI: 0.49-0.90 (P=0.007). Data from the GMDR showed that gene-environment interaction among rs3918242 and central obesity on the risk of NAFLD might be significant (P=0.001). By using the ULR method, subjects as central obesity-positive but with genotype CT/TT, appeared having 4.50 (95% CI: 2.78-7.17, P= 0.007) times risk of NAFLD, when compared to the central obesity-negative subjects with genotype CC after adjusting for the covariates. CONCLUSION: MMP-9 rs3918242, MMP-2 rs243865 were associated with risk of NAFLD while both rs3918242 and central obesity showing synergistic effects on the risk of the NAFLD. PMID- 26850404 TI - [Meta-analysis on causes of ulcerative colitis]. AB - OBJECTIVE: To analyze the main influencing factor of ulcerative colitis (UC). METHODS: Literature retrieval was conducted by using English databases (PubMed, Cochrane and Embase) and Chinese databases (CNKI, Wanfang, SinoMed and VIP) to collect the studies on the influencing factors of UC published both at home and abroad from January 2000 to October 2014. According to the inclusion and exclusion criteria, data were extracted and methodological quality was assessed. Then, a Meta-analysis was performed with Stata 12.0 software. RESULTS: A total of 24 case-control studies were included, involving 5 653 patients and 20 218 controls. The results of Meta-analysis showed that the influencing factors of UC would include family history of inflammatory bowel disease, ex-smoker, gastrointestinal infections, regular consumption of milk, fat diet, appendectomy, smoking and high educational level, with the pooled OR values as 4.68 (95%CI:3.59 6.11) , 1.81 (95%CI: 1.58-2.09) , 5.10 (95%CI: 2.38-10.92) , 2.26 (95%CI: 1.65 3.09) , 2.21 (95%CI: 1.49-3.27) , 0.40 (95%CI:0.32-0.51) , 0.44 (95%CI:0.32-0.60) and 0.50 (95%CI:0.36-0.69) , respectively. CONCLUSION: Current evidence showed that the risk factors influencing the incidence of UC were family history of inflammatory bowel disease, ex-smoker, gastrointestinal infections, regular consumption of milk and fat diet, whereas appendectomy, smoking and high educational level were protective factors for UC. PMID- 26850405 TI - [Meta-analysis on risk factors of multidrug resistant tuberculosis in China]. AB - OBJECTIVE: To synthetically evaluate the risk factors of multidrug resistant tuberculosis (MDR-TB) in China. METHODS: Chinese databases (CNKI, Wanfang, SinoMed and VIP) and English database (PubMed) were used to collect studies on risk factors for MDR-TB from 1990 to 2013. Meanwhile, relevant studies were manually retrieved. According to the inclusion and exclusion criteria, studies were screened, data were extracted and quality assessed. A Meta-analysis was performed by using Stata 11.0 software. RESULTS: Twenty five studies on the risk factors of MDR-TB were synthetically and quantitatively analyzed. The results of Meta-analysis showed that factors as: being Han ethnic group, history of tuberculosis treatment, pulmonary cavity, floating population, TB case contact history, regular medication, living in rural areas, and poor economy were associated with the incidence of MDR-TB, the pooled OR values were 3.12 (95%CI: 1.16-8.40) , 5.27 (95% CI:3.60-7.72) , 1.39 (95%CI:1.03-1.87) , 1.69 (95%CI: 1.07 2.68) , 4.34 (95%CI: 1.91-9.86) , 0.23 (95% CI: 0.16-0.35) , 1.86 (95% CI: 1.59 2.18) and 1.62 (95% CI: 1.34-1.96) , respectively. CONCLUSION: Factors as: being Han ethnic group, history of tuberculosis treatment, pulmonary cavity, floating population, TB case contact history, living in rural areas and poor economy were considered to be at risk of MDR-TB while regular medication might be a protective factor to MDR-TB. PMID- 26850406 TI - [Meta-analysis on the efficacy and adverse events of aspirin plus clopidogrel versus aspirin-monotherapy in patients with ischemic stroke or transient ischemic attack]. AB - OBJECTIVE: To present the systematic assessment on the efficacy and bleeding adverse events of dual-antiplatelet therapy with aspirin and clopidogrel versus aspirin-mono-antiplatelet therapy in patients with ischemic stroke or transient ischemic attack. METHODS: Retrieve randomized controlled trials conformed to the inclusion and exclusion criteria in Cochrane Library, Medline, Embase, and Web of Science electronic database, between January 1, 1998 and April 1, 2015. Cochrane Collaboration was used to assess the methodological quality of the included research papers. Stratification analysis was performed on factors as: race, subtypes of the disease, duration of follow-up and with or without clopidogrel loading dose, of the patients. RESULTS: A total of 7 studies were eligible for analysis, including 14 022 study objects. Data from Meta-analysis showed that dual-antiplatelet therapy, when compared to the mono-therapy group, could reduce the risk of recurrent stroke (RR=0.71, 95%CI: 0.61-0.84, P<0.001) , at the same time, increase the risk of bleeding events (RR=1.60, 95%CI: 1.46-1.76, P<0.001). Data derived from the Hierarchical analysis showed that the risk of stroke recurrence in Chinese population (RR=0.55, 95%CI: 0.34-0.89) was lower than recorded in other populations (RR=0.78, 95%CI: 0.66-0.93) , with the risks of bleeding events as RR=1.41 (95%CI: 1.01-1.96) and RR=1.62 (95%CI: 1.47-1.79) , respectively. Risk of recurrence among the group with clopidogrel loading dose (RR=0.69, 95%CI: 0.58-0.81) was less than those without (RR=0.74, 95%CI:0.56 0.99). The risks of occurrence on bleeding events were RR=1.59 (95%CI: 1.10-2.30) and RR=1.60 (95%CI: 1.46-1.77) , respectively. CONCLUSION: The combined therapy of aspirin and clopidogrel could reduce the risk of recurrence of ischemic stroke and TIA patients, but increase the risk of bleeding, when compared to the group that using aspirin alone for the therapy. In Chinese population, the combined therapy seemed more effective than using aspirin alone in reducing the recurrence of stroke, but without increasing the risk of bleeding. PMID- 26850407 TI - [On 'social culture attribute of epidemiological variables']. PMID- 26850408 TI - [Research progress on survival analysis of highly antiretroviral therapy for HIV/AIDS]. PMID- 26850409 TI - [Situation on the research of Leptotrombidium rubellum]. PMID- 26850410 TI - Factors associated with the failure of first and second-line antiretroviral therapies therapy, a case control study in Cambodian HIV-1 infected children. AB - BACKGROUND: Little is known about the efficacy of first and and second-line antiretroviral therapies (ART) for HIV-1 infected children in resource limited Southeast Asian settings. Previous studies have shown that orphans are at a higher risk for virological failure (VF) in Cambodia. Consequently most of them required transfer to second-line ART. We assessed the factors associated with VF among HIV-1 infected children who were either under first-line (mostly 3TC + D4T + NVP) or under second-line (mostly ABC + DDI + LPV) therapies at a referral hospital in Cambodia. METHODS: A case-control study was conducted from February to July 2013 at the National Pediatric Hospital among HIV-1 infected children (aged 1-15 years) under second-line ART (cases) or first-line (matched controls at a ratio of 1:3) regimens. Children were included if a HIV-1 RNA plasma viral load (VL) result was available for the preceding 12 months. A standardized questionnaire explored family sociodemographics, HIV history, and adherence to ART. Associations between VF (HIV-1 RNA levels >=1000 copies/ml) and the children's characteristics were assessed using bivariate and multivariate analyses. RESULTS: A total of 232 children, 175 (75.4 %) under first-line and 57 (24.6 %) under second-line ART, for a median of 72.0 (IQR: 68.0-76.0) months, were enrolled. Of them, 94 (40.5 %) were double orphans and 51 (22.0 %) single orphans, and 77 (33.2 %) were living in orphanages. A total of 222 children (95.6 %) were deemed adherent to ART. Overall, 18 (7.7 %; 95 % CI 4.6-11.9) showed a VF, 14 (8.6 %; 95 % CI 4.8-14.0) under first-line and 4 (7.0 %; 95 % CI 1.9-17.0) under second-line ART (p = 0.5). Their median CD4 percentage was 8 % (IQR 2.9 12.9) at ART initiation. Children under second-line ART were older; more often double orphans, and had lower CD4 cell counts at the last control. In the multivariate analysis, having the last CD4 percentage below 15 % was the only factor associated with VF for ART regimen separately or when combined (OR 40.4; 95 % CI 11-134). CONCLUSIONS: The pattern of risk factors for VF in children is changing in Cambodia. Improved adherence evaluation and intensified monitoring of children with low CD4 counts is needed to decrease the risk of VF. PMID- 26850411 TI - Accurate, Automated Detection of Atrial Fibrillation in Ambulatory Recordings. AB - A highly accurate, automated algorithm would facilitate cost-effective screening for asymptomatic atrial fibrillation. This study analyzed a new algorithm and compared it to existing techniques. The incremental benefit of each step in refinement of the algorithm was measured, and the algorithm was compared to other methods using the Physionet atrial fibrillation and normal sinus rhythm databases. When analyzing segments of 21 RR intervals or less, the algorithm had a significantly higher area under the receiver operating characteristic curve (AUC) than the other algorithms tested. At analysis segment sizes of up to 101 RR intervals, the algorithm continued to have a higher AUC than any of the other methods tested, although the difference from the second best other algorithm was no longer significant, with an AUC of 0.9992 with a 95% confidence interval (CI) of 0.9986-0.9998, vs. 0.9986 (CI 0.9978-0.9994). With identical per-subject sensitivity, per-subject specificity of the current algorithm was superior to the other tested algorithms even at 101 RR intervals, with no false positives (CI 0.0 0.8%) vs. 5.3% false positives for the second best algorithm (CI 3.4-7.9%). The described algorithm shows great promise for automated screening for atrial fibrillation by reducing false positives requiring manual review, while maintaining high sensitivity. PMID- 26850412 TI - Statin Use, Diabetes Incidence and Overall Mortality in Normoglycemic and Impaired Fasting Glucose Patients. AB - BACKGROUND: The association between the use of statins and the risk of diabetes and increased mortality within the same population has been a source of controversy, and may underestimate the value of statins for patients at risk. OBJECTIVE: We aimed to assess whether statin use increases the risk of developing diabetes or affects overall mortality among normoglycemic patients and patients with impaired fasting glucose (IFG). DESIGN AND PARTICIPANTS: Observational cohort study of 13,508 normoglycemic patients (n = 4460; 33% taking statins) and 4563 IFG patients (n = 1865; 41% taking statin) among residents of Olmsted County, Minnesota, with clinical data in the Mayo Clinic electronic medical record and at least one outpatient fasting glucose test between 1999 and 2004. Demographics, vital signs, tobacco use, laboratory results, medications and comorbidities were obtained by electronic search for the period 1999-2004. Results were analyzed by Cox proportional hazards models, and the risk of incident diabetes and mortality were analyzed by survival curves using the Kaplan Meier method. MAIN MEASURES: The main endpoints were new clinical diagnosis of diabetes mellitus and total mortality. KEY RESULTS: After a mean of 6 years of follow-up, statin use was found to be associated with an increased risk of incident diabetes in the normoglycemic (HR 1.19; 95% CI, 1.05 to 1.35; p = 0.007) and IFG groups (HR 1.24; 95%CI, 1.11 to 1.38; p = 0.0001). At the same time, overall mortality decreased in both normoglycemic (HR 0.70; 95% CI, 0.66 to 0.80; p < 0.0001) and IFG patients (HR 0.77, 95% CI, 0.64 to 0.91; p = 0.0029) with statin use. CONCLUSION: In general, recommendations for statin use should not be affected by concerns over an increased risk of developing diabetes, since the benefit of reduced mortality clearly outweighs this small (19-24%) risk. PMID- 26850414 TI - "The Penitent Magdalene": Tiziano Vecellio (1488/1490-1576). PMID- 26850413 TI - Impact of Collaborative Care for Underserved Patients with PTSD in Primary Care: a Randomized Controlled Trial. AB - BACKGROUND: The effectiveness of collaborative care of mental health problems is clear for depression and growing but mixed for anxiety disorders, including posttraumatic stress disorder (PTSD). We know little about whether collaborative care can be effective in settings that serve low-income patients such as Federally Qualified Health Centers (FQHCs). OBJECTIVE: We compared the effectiveness of minimally enhanced usual care (MEU) versus collaborative care for PTSD with a care manager (PCM). DESIGN: This was a multi-site patient randomized controlled trial of PTSD care improvement over 1 year. PARTICIPANTS: We recruited and enrolled 404 patients in six FQHCs from June 2010 to October 2012. Patients were eligible if they had a primary care appointment, no obvious physical or cognitive obstacles to participation, were age 18-65 years, planned to continue care at the study location for 1 year, and met criteria for a past month diagnosis of PTSD. MAIN MEASURES: The main outcomes were PTSD diagnosis and symptom severity (range, 0-136) based on the Clinician-Administered PTSD Scale (CAPS). Secondary outcomes were medication and counseling for mental health problems, and health-related quality of life assessed at baseline, 6 months, and 12 months. KEY RESULTS: Patients in both conditions improved similarly over the 1 year evaluation period. At 12 months, PTSD diagnoses had an absolute decrease of 56.7% for PCM patients and 60.6% for MEU patients. PTSD symptoms decreased by 26.8 and 24.2 points, respectively. MEU and PCM patients also did not differ in process of care outcomes or health-related quality of life. Patients who actually engaged in care management had mental health care visits that were 14% higher (p < 0.01) and mental health medication prescription rates that were 15.2% higher (p < 0.01) than patients with no engagement. CONCLUSIONS: A minimally enhanced usual care intervention was similarly effective as collaborative care for patients in FQHCs. PMID- 26850416 TI - Progress through collaboration. PMID- 26850417 TI - Guidelines for reporting health economic research. AB - Health economic evaluations potentially provide valuable information to clinicians, health care administrators, and policy makers regarding the financial implications of decisions about the care of patients. The highest quality research should be used to inform decisions that have direct impact on the access to care and the outcome of treatment. However, economic analyses are often complex and use research methods which are relatively unfamiliar to clinicians. Furthermore, health economic data have substantial national, regional, and institutional variability, which can limit the external validity of the results of a study. Therefore, minimum guidelines that aim to standardise the quality and transparency of reporting health economic research have been developed, and instruments are available to assist in the assessment of its quality and the interpretation of results. The purpose of this editorial is to discuss the principal types of health economic studies, to review the most common instruments for judging the quality of these studies and to describe current reporting guidelines. Recommendations for the submission of these types of studies to The Bone & Joint Journal are provided. Cite this article: Bone Joint J 2016;98-B:147 51. PMID- 26850415 TI - Serum levels of the bone turnover markers dickkopf-1, sclerostin, osteoprotegerin, osteopontin, osteocalcin and 25-hydroxyvitamin D in Swedish geriatric patients aged 75 years or older with a fresh hip fracture and in healthy controls. AB - BACKGROUND: Bone turnover markers have a potential clinical use in describing bone remodeling and in predicting fractures. AIMS: In an elderly population >=75 years with a fresh hip fracture, and in healthy controls, investigate bone turnover markers and their relation to each other, to vitamin D status and to bone mineral density (BMD). METHODS: In a cross-sectional study serum levels of dickkopf-1 (DKK-1), sclerostin (SOST), osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, 25-hydroxyvitamin D (25(OH)D) were analyzed in 89 Swedish patients with a fresh hip fracture and in 82 healthy volunteers. Serum levels of bone markers were determined by Luminex technique. RESULTS: S-25-hydroxyvitamin D (S 25(OH)D) was decreased in patients compared to controls (48 +/- 21 vs. 76 +/- 25 nmol/L, p < 0.001). SOST, but none of the other bone turnover markers correlated with BMD (r = 0.50, p < 0.001). Compared with controls, higher levels of OPG (488 +/- 1.4 vs. 191 +/- 1.4 ng/L, p < 0.001), OPN (69 +/- 1.7 vs. 19 +/- 1.4 ug/L, p < 0.001), DKK-1 (273 +/- 1.7 vs. 168 +/- 1.7 ng/L, p < 0.001), and lower levels of osteocalcin (5.8 +/- 3.5 vs. 9.5 +/- 3.6 ug/L, p < 0.001), were found in the fracture group. Levels of OPG, DKK-1 and SOST in both groups were positively associated. S-25(OH)D concentration was not found to be strongly associated with any of the bone markers. CONCLUSIONS: In contrast to findings in other studies, we found no strong correlation between 25(OH)D and the investigated bone markers. Both in patients with a fresh hip fracture and in healthy elderly, DKK-1, SOST and OPG appear to be associated. This suggests a relevance in these relationships meriting further investigation. PMID- 26850420 TI - Current recommendations for assessing the reliability of a measurement tool: a survival guide for orthopaedic surgeons. AB - Previous standards for assessing the reliability of a measurement tool have lacked consistency. We reviewed the most current American Society for Testing and Materials and International Organisation for Standardisation (ISO) recommendations, and propose an algorithm for orthopaedic surgeons. When assessing a measurement tool, conditions of the experimental set-up and clear formulae used to compile the results should be strictly reported. According to these recent guidelines, accuracy is a confusing word with an overly broad meaning and should therefore be abandoned. Depending on the experimental conditions, one should be referring to bias (when the study protocol involves accepted reference values), and repeatability (sr, r) or reproducibility (SR, R). In the absence of accepted reference values, only repeatability (sr, r) or reproducibility (SR, R) should be provided. TAKE HOME MESSAGE: Assessing the reliability of a measurement tool involves reporting bias, repeatability and/or reproducibility depending on the defined conditions, instead of precision or accuracy. PMID- 26850418 TI - Cost effectiveness of surgical versus non-surgical treatment of adults with displaced fractures of the proximal humerus: economic evaluation alongside the PROFHER trial. AB - AIMS: A pragmatic multicentre randomised controlled trial (PROFHER) was conducted in United Kingdom National Health Service (NHS) hospitals to evaluate the clinical effectiveness and cost effectiveness of surgery compared with non surgical treatment for displaced fractures of the proximal humerus involving the surgical neck in adults. METHODS: A cost utility analysis from the NHS perspective was performed. Differences between surgical and non-surgical treatment groups in costs and quality adjusted life years (QALYs) at two years were used to derive an estimate of the cost effectiveness of surgery using regression methods. RESULTS: Patients randomised to receive surgical intervention accumulated mean greater costs and marginally lower QALYs than patients randomised to non-surgery. The surgical intervention cost a mean of L1758 more per patient (95% confidence intervals (CI) L1126 to L2389). Total QALYs for the surgical group were smaller than those for non-surgery -0.0101 (95% CI -0.13 to 0.11). The probability of surgery being cost effective was less than 10% given the current NICE willingness to pay at a threshold of L20 000 for an additional QALY. The results were robust to sensitivity analyses. DISCUSSION: The results suggest that current surgical treatment is not cost effective for the majority of displaced fractures of the proximal humerus involving the surgical neck in the United Kingdom's NHS. TAKE HOME MESSAGE: The results of this trial do not support the trend of increased surgical treatment for patients with displaced fractures of the proximal humerus involving the surgical neck within the United Kingdom NHS. PMID- 26850419 TI - New anti-resorptives and antibody mediated anti-resorptive therapy. AB - The ageing population and an increase in both the incidence and prevalence of cancer pose a healthcare challenge, some of which is borne by the orthopaedic community in the form of osteoporotic fractures and metastatic bone disease. In recent years there has been an increasing understanding of the pathways involved in bone metabolism relevant to osteoporosis and metastases in bone. Newer therapies may aid the management of these problems. One group of drugs, the antibody mediated anti-resorptive therapies (AMARTs) use antibodies to block bone resorption pathways. This review seeks to present a synopsis of the guidelines, pharmacology and potential pathophysiology of AMARTs and other new anti resorptive drugs. We evaluate the literature relating to AMARTs and new anti resorptives with special attention on those approved for use in clinical practice. Denosumab, a monoclonal antibody against Receptor Activator for Nuclear Factor Kappa-B Ligand. It is the first AMART approved by the National Institute for Health and Clinical Excellence and the US Food and Drug Administration. Other novel anti-resorptives awaiting approval for clinical use include Odanacatib. Denosumab is indicated for the treatment of osteoporosis and prevention of the complications of bone metastases. Recent evidence suggests, however, that denosumab may have an adverse event profile similar to bisphosphonates, including atypical femoral fractures. It is, therefore, essential that orthopaedic surgeons are conversant with these medications and their safe usage. TAKE HOME MESSAGE: Denosumab has important orthopaedic indications and has been shown to significantly reduce patient morbidity in osteoporosis and metastatic bone disease. PMID- 26850421 TI - Tranexamic acid: optimal blood loss management in surface replacement arthroplasty. AB - AIMS: This study investigated whether the use of tranexamic acid (TXA) decreased blood loss and transfusion related cost following surface replacement arthroplasty (SRA). METHODS: A retrospective review of patients treated with TXA during a SRA, who did not receive autologous blood (TXA group) was performed. Two comparison groups were established; the first group comprised of patients who donated their own blood pre-operatively (auto group) and the second of patients who did not donate blood pre-operatively (control). Outcomes included transfusions, post-operative haemoglobin (Hgb), complications, and length of post operative stay. RESULTS: Between 2009 and 2013, 150 patients undergoing SRA were identified for inclusion: 51 in the auto, 49 in the control, and 50 in the TXA group. There were no differences in the pre-operative Hgb concentrations between groups. The mean post-operative Hgb was 11.3 g/dL (9.1 to 13.6) in the auto and TXA groups, and 10.6 g/dL (8.1 to 12.1)in the control group (p = 0.001). Accounting for cost of transfusions, administration of TXA, and length of stay, the cost per patient was $1731, $339, and $185 for the auto, control and TXA groups, respectively. DISCUSSION: TXA use demonstrated higher post-operative Hgb concentrations when compared with controls and decreased peri-operative costs. TAKE HOME MESSAGE: Tranexamic acid safely limits allogeneic transfusion, maintains post-operative haemoglobin, and decreases direct and indirect transfusion related costs in surface replacement arthroplasty. PMID- 26850422 TI - International metal-on-metal multidisciplinary teams: do we manage patients with metal-on-metal hip arthroplasty in the same way? An analysis from the International Specialist Centre Collaboration on MOM Hips (ISCCoMH). AB - AIMS: There are many guidelines that help direct the management of patients with metal-on-metal (MOM) hip arthroplasties. We have undertaken a study to compare the management of patients with MOM hip arthroplasties in different countries. METHODS: Six international tertiary referral orthopaedic centres were invited to participate by organising a multi-disciplinary team (MDT) meeting, consisting of two or more revision hip arthroplasty surgeons and a musculoskeletal radiologist. A full clinical dataset including history, blood tests and imaging for ten patients was sent to each unit, for discussion and treatment planning. Differences in the interpretation of findings, management decisions and rationale for decisions were compared using quantitative and qualitative methods. RESULTS: Overall agreement between the orthopaedic centres and the recommended treatment plans for the ten patients with MOM hip implants was moderate (kappa = 0.6). Full agreement was seen in a third of cases, however split decisions were also seen in a third of cases. Units differed in their interpretation of the significance of the investigation findings and put varying emphasis on serial changes, in the presence of symptoms. DISCUSSION: In conclusion, the management of raised or rising blood metal ions, cystic pseudotumours and peri-acetabular osteolysis led to inconsistency in the agreement between centres. Coordinated international guidance and MDT panel discussions are recommended to improve consensus in decision making. TAKE HOME MESSAGE: A lack of evidence and the subsequent variation in regulator guidance leads to differences in opinions, the clinical impact of which can be reduced through a multi-disciplinary team approach to managing patients with MOM hip implants. Cite this article: Bone Joint J 2016;98 B:179-86. PMID- 26850423 TI - Delayed dislocation following metal-on-polyethylene arthroplasty of the hip due to 'silent' trunnion corrosion. AB - AIMS: We present a case series of ten metal-on-polyethylene total hip arthroplasties (MoP THAs) with delayed dislocation associated with unrecognised adverse local tissue reaction due to corrosion at the trunnion and pseudotumour formation. METHODS: The diagnosis was not suspected in nine of the ten patients (six female/four male; mean age 66 years), despite treatment in a specialist unit (mean time from index surgery to revision was 58 months, 36 to 84). It was identified at revision surgery and subsequently confirmed by histological examination of resected tissue. Pre-operative assessment and culture results ruled out infection. A variety of treatment strategies were used, including resection of the pseudotumour and efforts to avoid recurrent dislocation. RESULTS: The rate of complications was high and included three deep infections, two patients with recurrent dislocation, and one recurrent pseudotumour. CONCLUSION: This series (mean follow-up of 76 months following index procedure and 19 months following revision THA) demonstrates that pseudotumour is an infrequent but important contributor to delayed instability following MoP THA. It is easy to overlook in the differential diagnosis, especially if the alignment of the components is less than optimal, leading to an assumption that malalignment is the cause of the dislocation. The instability is likely to be multifactorial and the revision surgery is complex. TAKE HOME MESSAGE: Due to the high complication rate associated with revision in this cohort, the diagnosis should be borne in mind when counselling patients regarding the risks of revision surgery. PMID- 26850425 TI - Is a questionnaire and radiograph-based follow-up model for patients with primary hip and knee arthroplasty a viable alternative to traditional regular outpatient follow-up clinic? AB - AIMS: Increasing demand for total hip and knee arthroplasty (THA/TKA) and associated follow-up has placed huge demands on orthopaedic services. Feasible follow-up mechanisms are therefore essential. METHODS: We conducted an audit of clinical follow-up decision-making for THA/TKA based on questionnaire/radiograph review compared with local practice of Arthroplasty Care Practitioner (ACP)-led outpatient follow-up. In all 599 patients attending an ACP-led THA/TKA follow-up clinic had a pelvic/knee radiograph, completed a pain/function questionnaire and were reviewed by an ACP. An experienced orthopaedic surgeon reviewed the same radiographs and questionnaires, without patient contact or knowledge of the ACP's decision. Each pathway classified patients into: urgent review, annual monitoring, routine follow-up or discharge. RESULTS: In total, 401 hip and 198 knee patients were included. There was substantial agreement between the ACP and surgeon for both hip (kappa = 0.69, 95% confidence interval (CI) 0.62 to 0.76) and knee (kappa = 0.81, 95% CI 0.74 to 0.88). Positive agreement was very high for discharge and routine follow-up; however the ACP was more likely to select annual monitoring and the surgeon urgent review. DISCUSSION: Review of the questionnaire/radiograph together identified all patients in need of increased surveillance, with good agreement for on-going patient management. However, review of the radiograph or questionnaire alone missed some patients with potential problems. A radiograph in conjunction with a questionnaire as a review may represent a cost effective THA/TKA follow-up mechanism. TAKE HOME MESSAGE: A questionnaire and radiograph-based remote review may represent a cost-effective total joint arthroplasty follow-up mechanism; thereby reducing the considerable burden that follow-up currently places on the NHS. PMID- 26850424 TI - The impact of including corticosteroid in a periarticular injection for pain control after total knee arthroplasty: a double-blind randomised controlled trial. AB - There is conflicting evidence about the benefit of using corticosteroid in periarticular injections for pain relief after total knee arthroplasty (TKA). We carried out a double-blinded, randomised controlled trial to assess the efficacy of using corticosteroid in a periarticular injection to control pain after TKA. A total of 77 patients, 67 women and ten men, with a mean age of 74 years (47 to 88) who were about to undergo unilateral TKA were randomly assigned to have a periarticular injection with or without corticosteroid. The primary outcome was post-operative pain at rest during the first 24 hours after surgery, measured every two hours using a visual analogue pain scale score. The cumulative pain score was quantified using the area under the curve. The corticosteroid group had a significantly lower cumulative pain score than the no-corticosteroid group during the first 24 hours after surgery (mean area under the curve 139, 0 to 560, and 264, 0 to 1460; p = 0.024). The rate of complications, including surgical site infection, was not significantly different between the two groups up to one year post-operatively. The addition of corticosteroid to the periarticular injection significantly decreased early post-operative pain. Further studies are needed to confirm the safety of corticosteroid in periarticular injection. TAKE HOME MESSAGE: The use of corticosteroid in periarticular injection offered better pain relief during the initial 24 hours after TKA. PMID- 26850426 TI - Functional outcome and quality of life after traumatic total brachial plexus injury treated by nerve transfer or single/double free muscle transfers: a comparative study. AB - AIMS: Between 2002 and 2011, 81 patients with a traumatic total brachial plexus injury underwent reconstruction by double free muscle transfer (DFMT, 47 cases), single muscle transfer (SMT, 16 cases) or nerve transfers (NT, 18 cases). METHODS: They were evaluated for functional outcome and quality of life (QoL) using the Disability of Arm, Shoulder and Hand questionnaire, both pre- and post operatively. The three groups were compared and followed-up for at least 24 months. RESULTS: The mean shoulder abduction and flexion were comparable in all groups, but external rotation was significantly better in the DFMT group as were range and quantitative power of elbow flexion. Patients who had undergone DFMT had reasonable total active finger movement and hook grip strength. All groups showed improvement in function at a level greater than a minimum clinically important difference. The DFMT group showed the greatest improvement. DISCUSSION: Patients in the DFMT group had a better functional outcome and QoL recovery than those in the NT and SMT groups. TAKE HOME MESSAGE: Double free muscle transfer procedure is capable of restoring maximum function in patients of total brachial plexus palsy. PMID- 26850427 TI - The effect of glenosphere diameter and eccentricity on deltoid power in reverse shoulder arthroplasty. AB - AIMS: The eccentric glenosphere was principally introduced into reverse shoulder arthroplasty to reduce the incidence of scapular notching. There is only limited information about the influence of its design on deltoid power and joint reaction forces. The aim of our study was to investigate how the diameter and eccentricity of the glenosphere affect the biomechanics of the deltoid and the resultant joint reaction forces. METHODS: Different sizes of glenosphere and eccentricity were serially tested in ten cadaveric shoulders using a custom shoulder movement simulator. RESULTS: Increasing the diameter of the glenosphere alone did not alter the deltoid moment arm. However, using an eccentric glenosphere increased the moment arm of the deltoid, lowered the joint reaction force and required less deltoid force to generate movement. CONCLUSION: Eccentricity is an independent variable which increases deltoid efficiency and lowers joint reaction forces in a reverse shoulder arthroplasty. Cite this article: Bone Joint J 2016;98-B:218-23. PMID- 26850428 TI - Risk factors for blood transfusion after shoulder arthroplasty. AB - AIMS: Currently, there is little information about the need for peri-operative blood transfusion in patients undergoing shoulder arthroplasty. The purpose of this study was to identify the rate of transfusion and its predisposing factors, and to establish a blood conservation strategy. METHODS: We identified all patients who had undergone shoulder arthroplasty at our hospital between 1 January 2011 and 31 December 2013. The rate of transfusion was determined from the patient's records. While there were exceptions, patients typically underwent transfusion if they had a level of haemoglobin of < 7.5 g/dl if asymptomatic, < 9.0 g/dl if they had a significant cardiac history or symptoms of dizziness or light headedness. Multivariable regression analysis was undertaken to identify predictors of transfusion. High- and low-risk cohorts for transfusion were identified from a receiver operating characteristic (ROC) curve. RESULTS: Of 1174 shoulder arthroplasties performed on 1081 patients, 53 cases (4.5%) required transfusion post-operatively. Predictors of blood transfusion were a lower pre operative haematocrit (p < 0.001) and shoulder arthroplasty undertaken for post traumatic arthritis (p < 0.001). ROC analysis identified pre-operative haematocrit of 39.6% as a 90% sensitivity cut-off for transfusion. In total 48 of the 436 (11%) shoulder arthroplasties with a pre-operative haematocrit < 39.6% needed transfusion compared with five of the 738 (0.70%) shoulder arthroplasties with a haematocrit above this level. DISCUSSION: We found that transfusion was needed less frequently than previously described for shoulder arthroplasty. Patients with a pre-operative haematocrit < 39.6% should be advised that there is an increased risk for blood transfusion, while those with a haematocrit above this level are unlikely to require transfusion. TAKE HOME MESSAGE: The rate of transfusion after shoulder arthroplasty is under 5%, and those with a pre operative haematocrit greater than or equal to 39.6% have a very low likelihood (< 1%) of requiring a transfusion. PMID- 26850429 TI - Thoracolumbar kyphosis in patients with mucopolysaccharidoses: clinical outcomes and predictive radiographic factors for progression of deformity. AB - AIMS: Clinical and radiological data were reviewed for all patients with mucopolysaccharidoses (MPS) with thoracolumbar kyphosis managed non-operatively or operatively in our institution. METHODS: In all 16 patients were included (eight female: eight male; 50% male), of whom nine had Hurler, five Morquio and two Hunter syndrome. Six patients were treated non-operatively (mean age at presentation of 6.3 years; 0.4 to 12.9); mean kyphotic progression +1.5(o)/year; mean follow-up of 3.1 years (1 to 5.1) and ten patients operatively (mean age at presentation of 4.7 years; 0.9 to 14.4); mean kyphotic progression 10.8(o)/year; mean follow-up of 8.2 years; 4.8 to 11.8) by circumferential arthrodesis with posterior instrumentation in patients with flexible deformities (n = 6). RESULTS: In the surgical group (mean age at surgery of 6.6 years; 2.4 to 16.8); mean post operative follow-up of 6.3 years (3.5 to 10.3), mean pre-operative thoracolumbar kyphosis of 74.3(o) (42(o) to 110(o)) was corrected to mean of 28.6(o) (0(o) to 65(o)) post-operatively, relating to a mean deformity correction of 66.9% (31% to 100%). Surgical complications included a deep wound infection treated by early debridement, apical non-union treated by posterior re-grafting, and stable adjacent segment spondylolisthesis managed non-operatively. Thoracolumbar kyphosis > +38(o) at initial presentation was identified as predicting progressively severe deformity with 90% sensitivity and 83% specificity. DISCUSSION: This study demonstrates that severe thoracolumbar kyphosis in patients with MPS can be effectively treated by circumferential arthrodesis. Severity of kyphosis at initial presentation may predict progression of thoracolumbar deformity. Patients with MPS may be particularly susceptible to post-operative complications due to the underlying connective tissue disorder and inherent immunological compromise. TAKE HOME MESSAGE: Clinical and radiological data were reviewed for all patients with mucopolysaccharidoses with thoracolumbar kyphosis managed non-operatively or operatively in our institution. PMID- 26850430 TI - Restoration of the spinal canal volume in stenosis dependent on pedicle lengthening distance in pedicle-lengthening osteotomy: A three dimensional simulation. AB - AIMS: This study aimed to determine the relationship between pedicle-lengthening distance and bulge-canal volume ratio in cases of lumbar spinal stenosis, to provide a theoretical basis for the extent of lengthening in pedicle-lengthening osteotomies. METHODS: Three-dimensional reconstructions of CT images were performed for 69 patients (33 men and 36 women) (mean age 49.96 years; 24 to 81). Simulated pedicle-lengthening osteotomies and disc bulge and spinal canal volume calculations were performed using Mimics software. RESULTS: The mean spinal canal volume of the two groups, L4 and L5, were 14 646.81 mm(3) (5918.60 to 22 717.77) and 16 408.47 mm(3) (8678.21 to 31 204.79), respectively. The mean lengthening distance was 2.17 mm (0.5 to 4.8) and the mean bulge-canal volume ratio was 0.23 (0.05 to 0.48). The pedicle-lengthening distance of the two groups were very strongly correlated with disc bulge volume and bulge-canal volume ratio (p < 0.001); the predictive equation was established as L = 0.06 + 9.06R (where L equals the pedicle-lengthening distance and R represents the bulge-canal volume ratio). DISCUSSION: Our findings indicated that lumbar pedicle-lengthening distance strongly correlates with bulge-canal volume ratio, which can be estimated before surgery from CT images. TAKE HOME MESSAGE: The predictive equation could help surgeons to decide the pedicle lengthening distance according to individual's condition and guide the surgery effectively. PMID- 26850431 TI - Open reduction and internal fixation for the treatment of fractures of the lateral humeral condyle with an early delayed presentation in children: a radiological and clinical prospective study. AB - AIMS: The treatment of late presenting fractures of the lateral humeral condyle in children remains controversial. METHODS: We report on the outcome for 16 children who presented with a fracture of the lateral humeral epicondyle at a mean of 7.4 weeks (3 to 15.6) after injury and were treated surgically. RESULTS: The mean follow-up was four years (1.1 to 8.9), at which time the mean age of the patients was 8.7 years (3.2 to 17.8). The mean Dhillon functional score improved from 3.3 to 5.6 and the mean overall scores improved from 5.6 to 8.5. A total of seven patients had a fishtail deformity and eight had partial lateral epiphyseal closure. None had avascular necrosis. MRI showed an abnormal cartilage signal, incongruence of the joint surface and partial premature closure of the lateral physis in four patients. DISCUSSION: Neither age at the time of injury, the time interval between injury and operation, nor the pre-operative function were correlated with the incidence of complications. These results support the use of internal fixation for children with a lateral humeral epicondylar fracture with a delayed presentation. TAKE HOME MESSAGE: Open reduction and internal fixation yielded a satisfactory outcome within 16 weeks in children with a lateral humeral epicondylar fracture with a delayed presentation. PMID- 26850432 TI - Cost analysis of the surgical treatment of fractures of the proximal humerus: an evaluation of the determinants of cost and comparison of the institutional cost of treatment with the national tariff. AB - AIMS: The aims of this study were to estimate the cost of surgical treatment of fractures of the proximal humerus using a micro-costing methodology, contrast this cost with the national reimbursement tariff and establish the major determinants of cost. METHODS: A detailed inpatient treatment pathway was constructed using semi-structured interviews with 32 members of hospital staff. Its content validity was established through a Delphi panel evaluation. Costs were calculated using time-driven activity-based costing (TDABC) and sensitivity analysis was performed to evaluate the determinants of cost RESULTS: The mean cost of the different surgical treatments was estimated to be L3282. Although this represented a profit of L1138 against the national tariff, hemiarthroplasty as a treatment choice resulted in a net loss of L952. Choice of implant and theatre staffing were the largest cost drivers. Operating theatre delays of more than one hour resulted in a loss of income DISCUSSION: Our findings indicate that the national tariff does not accurately represent the cost of treatment for this condition. Effective use of the operating theatre and implant discounting are likely to be more effective cost containment approaches than control of bed-day costs. TAKE HOME MESSAGE: This cost analysis of fractures of the proximal humerus reinforces the limitations of the national tariff within the English National Health Service, and underlines the importance of effective use of the operating theatre, as well as appropriate implant procurement where controlling costs of treatment is concerned. PMID- 26850433 TI - Surgical hip dislocation according to Ganz for excision of osteochondromas in patients with multiple hereditary exostoses. AB - AIMS: We report a prospective cohort study of the midterm results of surgical dislocation of the hip (according to Ganz) to perform resection of osteochondromas involving the femoral neck in patients with multiple hereditary exostoses (MHE). METHODS: Hip range of movement (ROM) was assessed pre- and post operatively. Patients' judgment of post-operative reduction of pain, symptoms, the Rand 36-item Health Survey (RAND-36) and complications were analysed. RESULTS: Symptomatic osteochondromas of the femoral neck were removed in 20 hips (17 patients) between 2007 and 2012. There were nine men and eight women with a mean age at the time of surgery of 29 years (11 to 47). Mean follow-up was 46 months (26 to 73). At latest follow-up, mean ROM was significantly increased in all directions. Post-operatively the pain associated with the lesion was either significantly decreased or non-existent. There was a significant improvement in seven RAND-36 sub-domains. Encountered complications in four patients were pseudoarthrosis of the trochanteric osteotomy, traumatic separation of the trochanteric osteotomy, a pertrochanteric femoral fracture and avasvular necrosis. Histological analysis revealed osteochondromas in all hips. DISCUSSION: This study confirms the Ganz trochanteric flip osteotomy provided a reliable approach to osteochondromas of the femoral neck that are otherwise difficult to access for surgical resection. The procedure offered significant improvement in the quality of life, although one should be aware of the serious complications can arise despite the relatively safe procedure. TAKE HOME MESSAGE: When daily function and activities are affected, resection of osteochondromas of the proximal femur according to Ganz is indicated to significantly improve quality of life. PMID- 26850434 TI - Prognostic factors for patients with skeletal metastases from carcinoma of the breast. AB - AIMS: Surgical intervention in patients with bone metastases from breast cancer is dependent on the estimated survival of the patient. The purpose of this paper was to identify factors that would predict survival so that specific decisions could be made in terms of surgical (or non-surgical) management. METHODS: The records of 113 consecutive patients (112 women) with metastatic breast cancer were analysed for clinical, radiological, serological and surgical outcomes. Their median age was 61 years (interquartile range 29 to 90) and the median duration of follow-up was 1.6 years (standard deviation (sd) 1.9, 95% confidence interval (CI) 0 to 5.9). The cumulative one- and five-year rates of survival were 68% and 16% (95% Cl 60 to 77 and 95% CI 10 to 26, respectively). RESULTS: Linear discriminant analysis identified a 'quadruple A' predictor of survival by reclassifying the sum of the albumin, adjusted calcium, alkaline phosphatase and age covariates each multiplied by a determined factor. The accuracy of this 'quadruple A' predictor was 90% with a sensitivity of 100% and a specificity of 88%. A receiver operating characteristic (ROC) curve revealed an area under the curve of 79%. Survival analysis for this 'quadruple A' predictor (< = one or > one year survival) was statistically significant using the log rank test (p = 0.0004) and Cox proportional hazard (p = 0.001). Multivariate analysis showed the 'quadruple A' predictor to be the only independent predictor of survival (p = 0.01). DISCUSSION: The 'quadruple A' predictor, together with other positive predictors of survival, can be used by oncologists, orthopaedic and breast surgeons to estimate survival and therefore guide management. PMID- 26850435 TI - Prediction of survival after surgery due to skeletal metastases in the extremities. AB - AIMS: The purpose of this study was to develop a prognostic model for predicting survival of patients undergoing surgery owing to metastatic bone disease (MBD) in the appendicular skeleton. METHODS: We included a historical cohort of 130 consecutive patients (mean age 64 years, 30 to 85; 76 females/54 males) who underwent joint arthroplasty surgery (140 procedures) owing to MBD in the appendicular skeleton during the period between January 2003 and December 2008. Primary cancer, pre-operative haemoglobin, fracture versus impending fracture, Karnofsky score, visceral metastases, multiple bony metastases and American Society of Anaesthesiologist's score were included into a series of logistic regression models. The outcome was the survival status at three, six and 12 months respectively. Results were internally validated based on 1000 cross validations and reported as time-dependent area under the receiver-operating characteristic curves (AUC) for predictions of outcome. RESULTS: The predictive scores obtained showed AUC values of 79.1% (95% confidence intervals (CI) 65.6 to 89.6), 80.9% (95% CI 70.3 to 90.84) and 85.1% (95% CI 73.5 to 93.9) at three, six and 12 months. DISCUSSION: In conclusion, we have presented and internally validated a model for predicting survival after surgery owing to MBD in the appendicular skeleton. The model is the first, to our knowledge, built solely on material from patients who only had surgery in the appendicular skeleton. TAKE HOME MESSAGE: Applying this prognostic model will help determine whether the patients' anticipated survival makes it reasonable to subject them to extensive reconstructive surgery for which there may be an extended period of rehabilitation. Cite this article: Bone Joint J 2016;98-B:271-7. PMID- 26850436 TI - Predictors of outcome after single-event multilevel surgery in children with cerebral palsy: a retrospective ten-year follow-up study. AB - AIMS: Single event multilevel surgery (SEMLS) has been shown to improve gait in children with cerebral palsy (CP). However, there is limited evidence regarding long-term outcomes and factors influencing them. METHODS: In total 39 children (17 females and 22 males; mean age at SEMLS ten years four months, standard deviation 37 months) with bilateral CP (20 Gross Motor Function Classification System (GMFCS) level II and 19 GMFCS level III) treated with SEMLS were included. Children were evaluated using gait analysis and the Gait Deviation Index (GDI) before SEMLS and one, two to three, five and at least ten years after SEMLS. A linear mixed model was used to estimate the effect of age at the surgery, GMFCS and follow-up period on GDI. RESULTS: There was a mean improvement of 12.1 (-15.3 to 45.1) GDI points one year after SEMLS (p < 0.001) and 10.3 (-23.1 to 44.2) GDI points ten years after SEMLS compared with before SEMLS (p < 0.001). GMFCS level III children aged ten to 12 years had the most improvement. The GMFCS III group had more surgical procedures at the index SEMLS (p < 0.001) and during the follow up period (p = 0.039). After correcting for other factors, age at surgery was the only factor predictive of long-term results. Our model was able to explain 45% of the variance of the change in GDI at the different time points. TAKE HOME MESSAGE: Children with GMFCS III level aged ten to 12 are the benchmark responders to SEMLS in the long-term. PMID- 26850437 TI - Multilevel surgery in adults with cerebral palsy. AB - AIMS: Single-event multilevel surgery (SEMLS) has been used as an effective intervention in children with bilateral spastic cerebral palsy (BSCP) for 30 years. To date there is no evidence for SEMLS in adults with BSCP and the intervention remains focus of debate. METHODS: This study analysed the short-term outcome (mean 1.7 years, standard deviation 0.9) of 97 ambulatory adults with BSCP who performed three-dimensional gait analysis before and after SEMLS at one institution. RESULTS: Two objective gait variables were calculated pre- and post operatively; the Gillette Gait Index (GGI) and the Gait Profile Score (GPS). The results were analysed in three groups according to their childhood surgical history (group 1 = no surgery, group 2 = surgery other than SEMLS, group 3 = SEMLS). Improvements in gait were shown by a significant decrease of GPS (p = 0.001). Similar results were obtained for both legs (GGI right side and left side p = 0.01). Furthermore, significant improvements were found in all subgroups although this was less marked in group 3, where patients had undergone previous SEMLS. DISCUSSION: SEMLS is an effective and safe procedure to improve gait in adults with cerebral palsy. However, a longer rehabilitation period is to be expected than found in children. SEMLS is still effective in adult patients who have undergone previous SEMLS in childhood. TAKE HOME MESSAGE: Single-event multilevel surgery is a safe and effective procedure to improve gait disorders in adults with bilateral spastic cerebral palsy. PMID- 26850438 TI - Echocardiographic assessment of right ventricular functions in patients with proximal right coronary artery chronic total occlusion. AB - To assess right ventricular functions by echocardiography in patients with proximal right coronary artery (RCA) CTO and correlating it with clinical and angiographic variables. We studied 60 consecutive patients with CTO of the proximal RCA and no other significant lesions in the left coronary system. Echocardiography was performed in order to measure left ventricular (LV) dimensions, LVEF, RV end diastolic area (RVEDA), RV end systolic area (RVESA), RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), Doppler myocardial performance index (MPI), trans-tricuspid E and A waves, E/A ratio, S', e' and a'. Grades of coronary collaterals was assessed. Doppler MPI showed negative correlation with TAPSE (r = -0.8997, p < 0.0001) and RVFAC (r = -0.928, p < 0.0001). Positive correlation with trans-tricuspid E/A ratio (r = 0.893, p < 0.0001) and E/e' ratio (r = 0.783, p < 0.0001). Patients with no evidence of MI had more well-developed (grade 3) coronary collaterals (83.8 vs. 17.4 %). Patients with evidence of MI had lower RVFAC 38.13 +/- 5.39 versus 45.08 +/- 4.99 % (p < 0.0001), lower TAPSE 20.17 +/- 3.85 versus 25.35 +/- 3.46 mm (p < 0.0001), higher MPI 0.4 +/- 0.08 versus 0.31 +/- 0.05 (p < 0.0001), higher trans-tricuspid E/A ratio 1.79 +/- 0.38 versus 1.13 +/- 0.36 (p < 0.0001) and E/e' ratio 5.23 +/- 1.02 versus 3.61 +/- 0.88 (p < 0.0001). Patients with poorly developed collaterals had lower TAPSE and RVFAC and a higher MPI (p < 0.0001 for each). Patients with proximal RCA CTOs and evidence of inferior wall MI have significant impairment of RV functions in addition to poorly developed coronary collaterals. Those with proximal RCA CTOs and well-developed coronary collaterals have better RV functions. PMID- 26850439 TI - Emotion perception in adult attention-deficit hyperactivity disorder. AB - This study examined identification of emotional information in facial expression, prosody, and their combination in 23 adult patients with combined attention deficit-hyperactivity disorder (ADHD) versus 31 healthy controls (HC) matched for gender, age, and education. We employed a stimulus set which was carefully balanced for valence as well as recognizability of the expressed emotions as determined in an independent sample of HC to avoid potential biases due to different levels of task difficulty. ADHD patients were characterized by impaired recognition of all employed categories (neutral, happiness, eroticism, disgust, anger). Basic cognitive functions as assessed by neuropsychological testing, such as sustained attention, constancy of alertness, and verbal intelligence partially explained lower recognition rates. Removal of the correlated variance by means of regression analyses did not abolish lower performance in ADHD indicating deficits in social cognition independent of these neuropsychological factors (p < 0.05). Lower performance correlated with self-rated emotional intelligence (r = 0.38, p < 0.05) indicating that adults with ADHD are aware of their problems in emotion perception. ADHD patients could partly compensate their deficit in unimodal emotion perception by audiovisual integration as revealed by larger gains in emotion recognition accuracy during bimodal presentation (p < 0.05) as compared to HC. These behavioral results can serve as foundation for future neuroimaging studies and point rather towards sensory-specific regions than audiovisual integration areas in perception of emotional information in adult ADHD. PMID- 26850441 TI - Synergistic effect of calcium and zinc on glucose/xylose utilization and butanol tolerance of Clostridium acetobutylicum. AB - Biobutanol outperforms bioethanol as an advanced biofuel, but is not economically competitive in terms of its titer, yield and productivity associated with feedstocks and energy cost. In this work, the synergistic effect of calcium and zinc was investigated in the acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum using glucose, xylose and glucose/xylose mixtures as carbon source(s). Significant improvements associated with enhanced glucose/xylose utilization, cell growth, acids re-assimilation and butanol biosynthesis were achieved. Especially, the maximum butanol and ABE production of 16.1 and 25.9 g L(-1) were achieved from 69.3 g L(-1) glucose with butanol/ABE productivities of 0.40 and 0.65 g L(-1) h(-1) compared to those of 11.7 and 19.4 g/L with 0.18 and 0.30 g L(-1) h(-1) obtained in the control respectively without any supplement. More importantly, zinc was significantly involved in the butanol tolerance based on the improved xylose utilization under various butanol-shock conditions (2, 4, 6, 8 and 10 g L(-1) butanol). Under the same conditions, calcium and zinc co-supplementation led to the best xylose utilization and butanol production. These results suggested that calcium and zinc could play synergistic roles improving ABE fermentation by C. acetobutylicum. PMID- 26850440 TI - Isolation and identification of nematode-antagonistic compounds from the fungus Aspergillus candidus. AB - Culture medium from an isolate of the fungus Aspergillus candidus was extracted, fractionated and examined to discover compounds antagonistic to plant-parasitic nematodes that are important pathogens of agricultural crops. Column, thin layer and preparative chromatographies and spectral and elemental analyses, were used to isolate and identify two major constituents of an active fraction (Fraction F) obtained from the medium. Compound 1 was identified as 2-hydroxypropane-1, 2, 3 tricarboxylic acid (citric acid). Compound 2 was identified as 3-hydroxy-5 methoxy-3-(methoxycarbonyl)-5-oxopentanoic acid, an isomer of 1, 2-dimethyl citrate. Compound 1 and a citric acid standard, each tested at 50 mg mL(-1) in water, decreased hatch from eggs of the plant-parasitic nematode Meloidogyne incognita by more than 94%, and completely immobilized second-stage juveniles after 4-6 days exposure. Fraction F and Compounds 1 and 2 decreased the mobility of adults of the plant-parasitic nematode Ditylenchus destructor in vitro. Fraction F (25 mg mL(-1)) inhibited mobility >99% at 72 hrs. Compounds 1 and 2 (50 mg mL(-1)) each inhibited mobility more than 25% at 24 hr and more than 50% at 72 hr. This is the first assignment of nematode-antagonistic properties to specifically identified A. candidus metabolites. PMID- 26850442 TI - Single-stranded DNA phages: from early molecular biology tools to recent revolutions in environmental microbiology. AB - Single-stranded DNA (ssDNA) phages are profoundly different from tailed phages in many aspects including the nature and size of their genome, virion size and morphology, mutation rate, involvement in horizontal gene transfer, infection dynamics and cell lysis mechanisms. Despite the importance of ssDNA phages as molecular biology tools and model systems, the environmental distribution and ecological roles of these phages have been largely unexplored. Viral metagenomics and other culture-independent viral diversity studies have recently challenged the perspective of tailed, double-stranded DNA (dsDNA) phages, dominance by demonstrating the prevalence of ssDNA phages in diverse habitats. However, the differences between ssDNA and dsDNA phages also substantially limit the efficacy of simultaneously assessing the abundance and diversity of these two phage groups. Here we provide an overview of the major differences between ssDNA and tailed dsDNA phages that may influence their effects on bacterial communities. Furthermore, through the analysis of 181 published metaviromes we demonstrate the environmental distribution of ssDNA phages and present an analysis of the methodological biases that distort their study through metagenomics. PMID- 26850443 TI - T7-RNA polymerase dependent RNAi system in Aspergillus fumigatus: a proof of concept study. AB - An RNAi system based on T7 RNA polymerase (TRNAP) was designed and examined in Aspergillus fumigatus. This system consists of two elements; an inducible T7RNAP expressing cassette and an AMA1-based episomal RNAi plasmid. These constructs were transformed into the A. fumigatus protoplasts and the efficiency of this system was tested in downregulation of alb1 gene. Upon the induction of T7RNAP expression, the recombinant T7RNAP was able to recognize T7 promoters, which were located on the episomal plasmid and in opposite direction. As a result, the bidirectional transcription of alb1 fragment led to the silencing of the target gene. However, our results demonstrated that this silencing system is unstable and may not be applicable in preparation of RNAi libraries. PMID- 26850444 TI - Rumen ciliate protozoa of domestic sheep (Ovis aries) and goat (Capra aegagrus hircus) in Kyrgyzstan. AB - Species composition and concentration of rumen ciliate protozoa were investigated in the rumen contents of 14 domestic sheep and 1 goat living in Bishkek, Kyrgyzstan. This is the first report on rumen ciliates from ruminants living in Kyrgyzstan. In sheep 12 genera, 28 species and 12 morphotypes were detected, whereas in goat 8 genera, 12 species and 4 morphotypes were detected. The density of ciliates in sheep was (28.1 +/- 20.0) * 10(4) cells mL(-1) and in goat was 37.0 * 10(4) cells mL(-1). Dasytricha ruminantium, Isotricha prostoma, Entodinium simulans and Ophryoscolex caudatus were major species (100%) in sheep, and for the first time, Diplodinium rangiferi was detected in a domestic goat. PMID- 26850445 TI - Klinefelter syndrome, cardiovascular system, and thromboembolic disease: review of literature and clinical perspectives. AB - Klinefelter syndrome (KS) is the most frequently occurring sex chromosomal aberration in males, with an incidence of about 1 in 500-700 newborns. Data acquired from large registry-based studies revealed an increase in mortality rates among KS patients when compared with mortality rates among the general population. Among all causes of death, metabolic, cardiovascular, and hemostatic complication seem to play a pivotal role. KS is associated, as are other chromosomal pathologies and genetic diseases, with cardiac congenital anomalies that contribute to the increase in mortality. The aim of the current study was to systematically review the relationships between KS and the cardiovascular system and hemostatic balance. In summary, patients with KS display an increased cardiovascular risk profile, characterized by increased prevalence of metabolic abnormalities including Diabetes mellitus (DM), dyslipidemia, and alterations in biomarkers of cardiovascular disease. KS does not, however, appear to be associated with arterial hypertension. Moreover, KS patients are characterized by subclinical abnormalities in left ventricular (LV) systolic and diastolic function and endothelial function, which, when associated with chronotropic incompetence may led to reduced cardiopulmonary performance. KS patients appear to be at a higher risk for cardiovascular disease, attributing to an increased risk of thromboembolic events with a high prevalence of recurrent venous ulcers, venous insufficiency, recurrent venous and arterial thromboembolism with higher risk of deep venous thrombosis or pulmonary embolism. It appears that cardiovascular involvement in KS is mainly due to chromosomal abnormalities rather than solely on low serum testosterone levels. On the basis of evidence acquisition and authors' own experience, a flowchart addressing the management of cardiovascular function and prognosis of KS patients has been developed for clinical use. PMID- 26850446 TI - Postoperative sellar hematoma after pituitary surgery: clinical and biochemical characteristics. AB - BACKGROUND: Postoperative sellar hematoma can develop following surgery for pituitary tumors and other sellar masses such a Rathke's cleft cyst (RCC) due to continued blood oozing. Though often mild sellar hematoma can create mass effects that might impair pituitary function. AIM: This study summarizes the clinical and biochemical characteristics of sellar hematoma and explores the potential mechanisms for the associated hypopituitarism. PATIENTS AND METHODS: Sellar hematoma was suspected clinically (worsening headaches, visual impairment, and mental status alterations) and confirmed radiographically in 23 patients (18/279 with macroadenomas and in 5/92 with RCC). Postoperatively, patients were monitored without glucocorticoid therapy and all had appropriately normal HPA function before sellar hematoma diagnosis. RESULTS: The demographics of patients who had sellar hematoma were similar to those who did not. Biochemical changes at diagnosis included decreased plasma ACTH and its dependent steroids (cortisol, DHEA, and DHEA-S), concomitant mild hyperprolactinemia, and mild hyponatremia (P < 0.005 for all parameters). Treatment with glucocorticoids resulted in rapid clinical improvement in most patients. Glucocorticoid therapy was discontinued within 2 weeks and re-testing thereafter showed normal HPA function in 16/23. None of the patients without sellar hematoma had worsening in pituitary function, visual, or neurological symptoms. CONCLUSIONS: When large, sellar hematoma can lead to mass effect that causes headaches, visual symptoms, and acute and often reversible hypopituitarism manifesting initially as impaired HPA function. Rapid resolution is observed in most patients with glucocorticoid administration The rapid onset and reversibility of hypopituitarism associated with mild hyperprolactinemia suggest that compression of pituitary stalk/ portal vessels is likely the dominant mechanism of pituitary dysfunction in this setting. PMID- 26850447 TI - Impact of laparoscopic cystectomy of endometriotic and non-endometriotic cysts on ovarian volume, antral follicle count (AFC) and ovarian doppler velocimetry. AB - OBJECTIVE: To evaluate the effect on ovarian reserve and blood flow of unilateral laparoscopic stripping of endometriotic versus non-endometriotic cysts. DESIGN: Prospective observational study. SETTING: Tertiary university gynecology unit. PATIENTS: During the study period, 71 subjects underwent the first laparoscopic surgery for removal of a monolateral benign ovarian cyst. INTERVENTIONS: Trans vaginal ultrasound scans of the pelvis about six months after surgery. MAIN OUTCOME MEASURES: Ovarian volume, Antral Follicle Count (AFC) and Resistance Index (RI) of ovarian artery of the operated and the contralateral ovary. RESULTS: Among 71 cysts, 39.4% were endometriotic and 60.6% non-endometriotic benign cysts. All the procedures were performed by the same experienced surgeons with a standardized technique. No major complications were reported during surgery. The mean (+/-SD) age and BMI of women were 31.0 +/- 6.8 years and 24.2 +/- 3.3 kg/m(2), respectively. Mean diameter of the removed cysts was smaller for endometriotic than non-endometriotic cysts (4.35 +/- 1.77 cm versus 6.33 +/- 3.71 cm, p = 0.046). In comparison to non-operated, volume of the operated ovary was significantly lower and with a reduced AFC, with no difference between endometriotic and non-endometriotic cysts (-2.41 +/- 2.35 versus -2.00 +/- 2.23 cm(3), p = 0.496) (-3.45 +/- 3.07 versus -2.43 +/- 1.95, p = 0.11). Ovarian artery RI was higher in the operated ovary with no difference between endometriotic and non-endometriotic cysts (0.19 +/- 0.14 versus 0.14 +/- 0.10, p = 0.455). The difference in ovarian volume (r = 0.178), AFC (r = 0.094) and RI (r = 0.079) between operated and non-operated ovary was not dependent on the diameter of the removed cyst. CONCLUSION: Ovarian surgery is associated with a decline of ovarian reserve, independently on the histological type and the diameter of the removed cyst. PMID- 26850449 TI - Carbohydrate dependence during prolonged simulated cycling time trials. AB - PURPOSE: We determined the effect of suppressing lipolysis via administration of Nicotinic acid (NA) and pre-exercise feeding on rates of whole-body substrate utilisation and cycling time trial (TT) performance. METHODS: In a randomised, single-blind, crossover design, eight trained male cyclists/triathletes completed two series of TTs in which they performed a predetermined amount of work calculated to last ~60, 90 and 120 min. TTs were undertaken after a standardised breakfast (2 g kg(-1) BM of carbohydrate (CHO)) and ingestion of capsules containing either NA or placebo (PL). RESULTS: Plasma [free fatty acids] were suppressed with NA, but increased in the later stages of TT90 and TT120 with PL (p < 0.05). There was no treatment effect on time to complete TT60 (60.4 +/- 4.1 vs. 59.3 +/- 3.4 min) or TT90 (90.4 +/- 9.1 vs. 89.5 +/- 6.6 min) for NA and PL, respectively. However, TT120 was slower with NA (123.1 +/- 5.7 vs. 120.1 +/- 8.7 min, p < 0.001), which coincided with a decline in plasma [glucose] during the later stages of this ride (p < 0.05). For TTs of the same duration, the rates of whole-body CHO oxidation were unaffected by NA, but decreased with increasing TT time (p < 0.05). CHO was the predominant substrate for all TTs contributing between 83 and 94 % to total energy expenditure, although there was a small use of lipid-based fuels for all rides. CONCLUSION: (1) NA impaired cycling TT performance lasting 120 min, (2) cycling TTs lasting from 60 to 120 min are CHO dependent, and (3) there is an obligatory use of lipid-based fuels in TTs lasting 1-2 h. PMID- 26850448 TI - Fusion cytokine IL-2-GMCSF enhances anticancer immune responses through promoting cell-cell interactions. AB - BACKGROUND: Potent antitumor responses can be induced through cytokine immunotherapy. Interleukin (IL)-2 and granulocyte-macrophage colony-stimulating factor (GM-CSF) are among the most effective cytokines to induce tumor-specific systemic immune responses and can act synergistically. To overcome the limitations of combined use of these two cytokines, we have constructed an IL2 GMCSF fusion protein and characterized its antitumor effects in this study. METHODS: The expression of IL-2 receptor and GM-CSF receptor of cell lines were detected with quantitative real-time PCR. On this basis, the bioactivities of IL2 GMCSF, especially effects on DC2.4 cells were assayed. Another function of IL2 GMCSF-bridge two types of cells-was assessed by cell contact counting and cytotoxicity assays. The anti-tumor activity in vivo of IL2-GMCSF was evaluated in the melanoma model. The statistical significance among treatment groups were determined by One-Way ANOVA. RESULTS: The fusion protein IL2-GMCSF maintained the activities of IL-2 and GM-CSF, and could significantly promote DC2.4 cell activities, including phagocytosis, proliferation and cytokine secretion. In addition to the inherent cytokine activity, IL2-GMCSF bridges direct cell-cell interactions and enhances splenocyte killing efficacy against multiple tumor cell lines in vitro. Co-injection of IL2-GMCSF and inactivated B16F10 mouse melanoma cells induced complete immunoprotective responses in about 30 % of mice. CONCLUSION: These results suggested that IL2-GMCSF can efficiently regulate immune responses against tumors. Furthermore, as the bridging effect relies on both IL-2R and GM-CSFR and promotes interactions between immune and tumor cells, IL2-GMCSF may be utilized as a useful tool for dissecting specific immune responses for future clinical applications. PMID- 26850450 TI - Modulation of inflammasome activity by Porphyromonas gingivalis in periodontitis and associated systemic diseases. AB - Inflammasomes are large multiprotein complexes localized in the cytoplasm of the cell. They are responsible for the maturation of pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) and IL-18 as well as for the activation of inflammatory cell death, the so-called pyroptosis. Inflammasomes assemble in response to cellular infection, cellular stress, or tissue damage; promote inflammatory responses and are of great importance in regulating the innate immune system in chronic inflammatory diseases such as periodontitis and several chronic systemic diseases. In addition to sensing cellular integrity, inflammasomes are involved in the homeostatic mutualism between the indigenous microbiota and the host. There are several types of inflammasomes of which NLRP3 is best characterized in microbial pathogenesis. Many opportunistic bacteria try to evade the innate immune system in order to survive in the host cells. One of these is the periodontopathogen Porphyromonas gingivalis which has been shown to have several mechanisms of modulating innate immunity by limiting the activation of the NLRP3 inflammasome. Among them, ATP-/P2X7- signaling is recently associated not only with periodontitis but also with development of several systemic diseases. The present paper reviews multiple mechanisms through which P. gingivalis can modify innate immunity by affecting inflammasome activity. PMID- 26850452 TI - Erratum to: What drives junior doctors to use clinical practice guidelines? A national cross-sectional survey of foundation doctors in England & Wales. PMID- 26850451 TI - Child maltreatment victimization by type in relation to criminal recidivism in juvenile offenders. AB - BACKGROUND: This study aimed to examine the relation between different types of child abuse victimization and criminal recidivism among juvenile offenders. METHOD: Secondary analyses were conducted on data collected with the Washington State Juvenile Court Assessment and general recidivism. The sample consisted of female (n = 3502) and male (n = 10,111) juvenile offenders. RESULTS: For male juvenile offenders, neglect and physical abuse victimization were significantly but rather weakly associated with both general and violent recidivism. For female juvenile offenders, neglect and physical abuse were weakly associated with general recidivism, but not with violent recidivism. Sexual abuse was not related to either general or violent recidivism in both male and female juvenile offenders. Most associations between dynamic (treatable) risk domains and recidivism were stronger in male juvenile offenders than in female juvenile offenders. In addition, most risk domains were more strongly related to general recidivism than to violent felony recidivism. For male juvenile offenders, neglect victimization was uniquely related to general recidivism whereas physical abuse victimization was uniquely related to violent recidivism, over and above dynamic risk factors for recidivism. For female juvenile offenders none of the maltreatment variables were uniquely related to general or violent felony recidivism. CONCLUSIONS: Childhood experiences of neglect and physical abuse predict reoffending in male juvenile offenders, pointing at a possible need to address these in risk management interventions. PMID- 26850453 TI - Group psychotherapy for female adult survivors of interpersonal psychological trauma: a preliminary study in Scotland. AB - BACKGROUND: There is limited evidence on manualised group interventions that facilitate the development of trauma recovery skills, affect regulation and meaning making for survivors of interpersonal trauma. AIM: The study aimed to provide preliminary evidence on the effectiveness of group psychotherapy (based on Trauma Recovery and Empowerment Model, TREM) for psychological distress in adult survivors of interpersonal trauma. METHOD: Participants were a consecutive series of female patients (n = 71) from the waiting lists of five National Health Service (NHS) Boards in Scotland. Participants completed a set of self-rated measures (PCL, CORE, SCL-90, DES and RSES) at baseline, mid-intervention, post intervention and 3-month follow-up. RESULTS: Effect sizes were small to medium across measures and assessment points at post-treatment and follow-up. With regard to clinical significance, at post-treatment, a proportion of 9.9% to 54.9% of participants achieved clinical significance across measures. At follow-up, a proportion of 9.9% to 62.0% of participants achieved clinical significance across measures. CONCLUSIONS: Group psychotherapy may be useful for a proportion of participants and especially so for symptoms of dissociation and self-esteem. Survivors of interpersonal trauma should be offered a choice of individual or group treatment modalities to reduce drop-out rate and maximise outcomes. PMID- 26850455 TI - David Oliver: Doctors need intergenerational solidarity. PMID- 26850456 TI - Experience of implementing the integrated TB model in Zhejiang, China: a retrospective observational study. AB - BACKGROUND: This study aims to assess the implementation of the TB control program under the integrated model in China where TB diagnosis and treatment is provided in TB designated hospitals. METHODS: Six counties under the integrated model in Zhejiang were randomly selected. TB referral and tracing was analyzed based on routine TB reporting data between January and December 2009 from county TB dispensaries. Regarding treatment and community management, we conducted face to-face surveys with 50 new TB patients randomly selected from each county, and reviewed their medical charts. RESULTS: A total of 7090 persons with presumptive TB were reported in 2009, of whom, 66.7% (4732/7090) were referred by other health facilities to TB designated hospitals, while 80.2% (3795/4732) were successfully referred. In total, 301 patients were surveyed and had a median medical expenditure of US$192. Ten percent (31/301) missed at least one dose during their treatment, and 64.5% (194/301) received direct observation, mostly by family members. CONCLUSIONS: The integrated model performed better on case referral and community management, but higher medical expenditures than those reported by studies under the dispensary model in China. Clear guidelines should be issued on supervising TB treatment in designated hospitals. PMID- 26850454 TI - [Mucosa-associated lymphoid tissue-derived (MALT) lymphoma]. AB - Pulmonary Mucosa-Associated Lymphoid Tissue (MALT)-type lymphoma is the most frequent primary pulmonary lymphoma. We report the case of a patient who presented a pulmonary MALT-type lymphoma treated with chloraminophen, with a recurrence 5 years later characterized with pulmonary lesions associated with a gastric location. This observation underlines some anatomical and clinical aspects of pulmonary MALT-type lymphoma, and leads to discuss the evolution of its physiopathological and therapeutic concepts. In particular, the contributions of positron emission tomography and molecular biology allow the analysis of possible multifocal affections of this disease. PMID- 26850457 TI - The Nursing Ethics Heritage Project. PMID- 26850458 TI - Decolonising research practices with the ethics of care. PMID- 26850459 TI - Ethical aspects of nurses thought 'too fat to care'. PMID- 26850463 TI - Topical delivery of paclitaxel for treatment of skin cancer. AB - CONTEXT: Skin cancer represents the most growing types of cancer in human and ultraviolet radiation can be cited as one of the prime factor for its occurrence. Current therapy of skin cancer suffers from numerous side effects; for effective therapy, topical application of formulation of paclitaxel (PTX) can be considered as a novel approach. OBJECTIVE: The present study is an attempt to prepare formulation of solid lipid nanoparticles (SLN) of PTX for the effective treatment of various form of skin carcinoma. METHODS: The SLN were prepared by high-speed homogenization and ultrasonication method. The prepared SLN were characterized. The optimized PTX SLN were loaded in carbopol gel. The prepared gels were evaluated for its gelling properties and finally studied for in vivo anti-cancer efficacy and histopathological study. RESULTS: The particle size distribution was found to be in the range of 78.82-587.8 nm. The product yield (%) was found between 60% and 66% and showed a highest entrapment efficiency of 68.3%. The in vitro release of the drug from SLN dispersion was found to be biphasic with the initial burst effect, followed by slow release. SLN-loaded gel were subjected to permeability study and the results show steady-state flux (Jss), permeability coefficient (Kp), and enhancement ratio were significantly increased in SLN loaded gel formulation as compared with PTX-loaded gel. The histopathological study clearly reveals the efficacy of the SLN-F3 3G in the treatment of skin cancer. CONCLUSION: The experimental formulations show controlled release of PTX and thus expected to show reduce dose-related side effects. PMID- 26850464 TI - Uterine lavage is efficient to recover endometrial cytology sample and does not interfere with fertility rate after artificial insemination in cows. AB - Productivity rates directly depend on the fertility of a herd, which in turn can be influenced by many factors. Semen deposited in the female reproductive tract is foreign to the body and, in response to this invasion, produces an inflammatory reaction, which is characterized by rapid infusion of polymorphonuclear (PMN) cells. Techniques to obtain an endometrial sample are usually invasive and can mask the true inflammatory response. Ultrasound is a noninvasive technique and can contribute to the diagnosis of postartificial insemination (AI) inflammatory response in cattle. The present study was divided into two experiments. The aim of experiment 1 was to compare two methods of endometrial cytology collection, uterine cytobrush (UC) and uterine lavage (UL), and their effects on uterine hemodynamics that provide information about blood flow. The two methods were evaluated by Doppler ultrasound using the spectral and color modes. For that purpose, 19 Nellore cows were synchronized for timed AI and subjected to UC (n = 9) or UL (n = 10). The techniques were performed 4 hours after AI. The results showed that both techniques allow collection of a good quality sample and with enough PMN cells to perform counting. More PMN cells were obtained by UL than UC. There was no difference in uterine blood flow between the UC and UL groups in any of the periods evaluated (34 hours before and 4, 24, and 48 hours after collection of uterine sample). On the basis of results of experiment 1, the effect of UL on fertility was studied in experiment 2. A total of 128 Nellore cows were synchronized for TAI; 35 cows were subjected to endometrial cytology by UL 4 hours after AI, and 93 were not submitted to any procedure (control). Pregnancy diagnosis was performed by transrectal ultrasound 30 days after AI. Pregnancy rates did not differ between UL (54.29%) and control (56.99%) groups. The results of this study showed that UL allows the collection of more representative cells of the surface of the uterus than UC technique and causes no damage to the reproductive tract. Moreover, UL did not affect pregnancy rate when performed 4 hours after AI. PMID- 26850462 TI - miR-155 Overexpression Promotes Genomic Instability by Reducing High-fidelity Polymerase Delta Expression and Activating Error-Prone DSB Repair. AB - miR-155 is an oncogenic miRNA that is often overexpressed in cancer and is associated with poor prognosis. miR-155 can target several DNA repair factors, including RAD51, MLH1, and MSH6, and its overexpression results in an increased mutation frequency in vitro, although the mechanism has yet to be fully understood. Here, we demonstrate that overexpression of miR-155 drives an increased mutation frequency both in vitro and in vivo, promoting genomic instability by affecting multiple DNA repair pathways. miR-155 overexpression causes a decrease in homologous recombination, but yields a concurrent increase in the error-prone nonhomologous end-joining pathway. Despite repressing established targets MLH1 and MSH6, the identified mutation pattern upon miR-155 overexpression does not resemble that of a mismatch repair-deficient background. Further investigation revealed that all four subunits of polymerase delta, a high fidelity DNA replication, and repair polymerase are downregulated at the mRNA level in the context of miR-155 overexpression. FOXO3a, a transcription factor and known target of miR-155, has one or more putative binding site(s) in the promoter of all four polymerase delta subunits. Finally, suppression of FOXO3a by miR-155 or by siRNA knockdown is sufficient to repress the expression of the catalytic subunit of polymerase delta, POLD1, at the protein level, indicating that FOXO3a contributes to the regulation of polymerase delta levels. IMPLICATIONS: Taken together, miR-155 overexpression drives an increase in mutation frequency via multifaceted impact on DNA damage response and DNA repair pathways. PMID- 26850465 TI - Immortalization of porcine placental trophoblast cells through reconstitution of telomerase activity. AB - Placental trophoblast cells (PTCs) play a critical role in histotrophic nutrient absorption, gaseous exchange, endocrine activities, and barrier function between the maternal and fetal systems. Establishment of immortalized porcine PTCs will help us to investigate the potential effects of different viruses on porcine trophoblast. In the present study, primary porcine PTCs were isolated from healthy gilts at Day 30 to Day 50 of gestation through collagenase digestion, percoll gradient centrifugation, and anti-CD9 immunomagnetic negative selection. To provide stable and long lifespan cells, primary PTCs were transfected with human telomerase reverse transcriptase (hTERT) gene. One porcine placental trophoblast cell line, named as hTERT-PTCs, was chosen for characterization. Human telomerase reverse transcriptase-PTCs achieved an extended replicative lifespan without exhibiting any neoplastic transformation signs in vivo or in vitro. The morphologic and key physiological characteristics of the immortalized PTCs were similar to primary PTCs. The immortalized PTCs retained original cell polarity and normal karyotype, expressed trophoblast-specific marker cytokeratin 7 and E-cadherin but did not express vimentin and major histocompatibility complex class I antigens as well as primary PTCs. Human telomerase reverse transcriptase-PTCs secreted low levels of chorionic gonadotrophin beta-subunit and placental lactogen that were coincident with primary PTCs. Taken together, our results demonstrated that the porcine PTCs could be immortalized through reconstitution of telomerase activity. The immortalized PTCs maintained its original characteristics and can be used as a model cells line to study the pathologic changes of porcine placental trophoblast in viruses infectious diseases. PMID- 26850466 TI - Pterostilbene carboxaldehyde thiosemicarbazone, a resveratrol derivative inhibits 17beta-Estradiol induced cell migration and proliferation in HUVECs. AB - Angiogenesis plays important roles in tumor growth and metastasis, thus development of a novel angiogenesis inhibitor is essential for the improvement of therapeutics against cancer. Thrombospondins-1 (TSP-1) is a potent endogenous inhibitor of angiogenesis that acts through direct effects on endothelial cell migration, proliferation, survival, and activating apoptotic pathways. TSP-1 has been shown to disrupt estrogen-induced endothelial cell proliferation and migration. Here we investigated the potential of pterostilbene carboxaldehyde thiosemicarbazone (PTERC-T), a novel resveratrol (RESV) derivative, to inhibit angiogenesis induced by female sex steroids, particularly 17beta-Estradiol (E2), on Human umbilical vein endothelial cells (HUVECs) and to elucidate the involvement of TSP-1 in PTERC-T action. Our results showed that PTERC-T significantly inhibited 17beta-E2-stimulated proliferation of HUVECs and induced apoptosis as determined by annexin V/propidium iodide staining and cleaved caspase-3 expression. Furthermore, PTERC-T also inhibited endothelial cell migration, and invasion in chick chorioallantoic membrane (CAM) assay. In contrast, RESV failed to inhibit 17beta-E2 induced HUVECs proliferation and invasion at similar dose. PTERC-T was also found to increase TSP-1 protein expression levels in a dose-dependent manner which, however, was counteracted by co-incubation with p38MAPK or JNK inhibitors, suggesting involvement of these pathways in PTERC-T action. These results suggest that the inhibitory effect of PTERC-T on 17beta-E2 induced angiogenesis is associated, at least in part, with its induction of endothelial cell apoptosis and inhibition of cell migration through targeting TSP-1. Thus, PTERC-T could be considered as a potential lead compound for developing a class of new drugs targeting angiogenesis-related diseases. PMID- 26850469 TI - Accessibility of observable and unobservable characteristics in autobiographical memories of recent and distant past. AB - Self-reports regarding how people visualise themselves during events that occurred in the past show that for events from the distant past individuals report assuming a more external perspective than for events from the recent past [Nigro, G., & Neisser, U. (1983). Point of view in personal memories. Cognitive Psychology, 15, 467-482; Pronin, E., & Ross, L. (2006). Temporal differences in trait self-ascription. Journal of Personality & Social Psychology, 90, 197-209]. Thus it appears that, with the passage of time, representations of self embodied in memories of past events lose their position of an insider and assume a more ordinary position of self as an object seen from the perspective of an outside observer. The purpose of the present experiment was to examine this shift using a performance-based measure of accessibility. Results showed that self-judgements regarding unobservable, covert characteristics were faster for recent-compared to more distant-autobiographical events. However, self-judgements regarding observable, overt characteristics were faster for more distant events. This suggests an accessibility-based mechanism underlying the shift from internal to the relatively more external perspective in forming self-images related to the distant past. PMID- 26850467 TI - Estrogen stimulated migration and invasion of estrogen receptor-negative breast cancer cells involves an ezrin-dependent crosstalk between G protein-coupled receptor 30 and estrogen receptor beta signaling. AB - Estrogen mediates important cellular activities in estrogen receptor negative (ER ) breast cancer cells via membrane associated G protein-coupled receptor 30 (GPR30). However, the biological role and mechanism of estrogen action on cell motility and invasion in this aggressive kind of tumors remains poorly understood. We showed here that treatment with 17beta-estradiol (E2) in ER negative cancer cells resulted in ezrin-dependent cytoskeleton rearrangement and elicited a stimulatory effect on cell migration and invasion. Mechanistically, E2 induced ezrin activation was mediated by distinct mechanisms in different cell contexts. In SK-BR-3 cells with a high GPR30/ERbeta ratio, silencing of GPR30 was able to abolish E2 induced ERK1/2, AKT phosphorylation and ezrin activation, whereas in MDA-MB-231 cells with low GPR30/ERbeta ratio, E2 stimulated ezrin activation was mediated by the ERbeta/PI3K/AKT signaling pathway. Importantly, we showed that activation of GPR30 signaling significantly prevents ERbeta activation induced ezrin phosphorylation, cell migration and invasion, indicating an antagonist effect between GPR30 and ERbeta signaling in MDA-MB-231 cells. These findings highlight the important interplay between different estrogen receptors in estrogen induced cell motility and invasiveness in ER-negative breast cancer cells. PMID- 26850468 TI - Acetylcholinesterase inhibitory activity and molecular docking study of steroidal alkaloids from Holarrhena pubescens barks. AB - An alkaloidal extract of the bark of Holarrhena pubescens showed several inhibition zones of acetylcholinesterase (AChE) inhibitor, using a bioautographic assay. Activity-guided fractionation afforded three new steroidal alkaloids, mokluangins A-C (1-3), together with three known compounds, antidysentericine (4), holaphyllamine (5), methylholaphyllamine (6). All structures were elucidated by analysis of NMR and MS spectroscopic data. Compound 2 showed moderate antibacterial activity against Bacillus subtilis and Escherichia coli with the MIC value of 16 MUg/mL, while compound 3 exhibited moderate selective activity against E. coli with the MIC value of 16 MUg/mL. In addition, compounds 1-4 also showed strong AChE inhibiting activity with IC50 values ranging from 1.44 to 23.22 MUM. Molecular docking calculations were also performed and the results demonstrated that all compounds can bind at the aromatic gorge of AChE with estimated binding free energies correlated well with the in vitro inhibitory profiles. Hydrophobic and hydrogen bonding interactions contribute mainly to the binding of the alkaloids where the substituents at C-3 serving as key functional groups for the AChE inhibition. Our results will allow the development of new AChE-inhibitors based on steroidal alkaloid skeleton bearing the cyclic amide moiety. PMID- 26850470 TI - Perceptual Detection of Subtle Dysphonic Traits in Individuals with Cervical Spinal Cord Injury Using an Audience Response Systems Approach. AB - OBJECTIVES: Reduced respiratory function following lower cervical spinal cord injuries (CSCIs) may indirectly result in vocal dysfunction. Although self reports indicate voice change and limitations following CSCI, earlier efforts using global perceptual ratings to distinguish speakers with CSCI from noninjured speakers have not been very successful. We investigate the use of an audience response system-based approach to distinguish speakers with CSCI from noninjured speakers, and explore whether specific vocal traits can be identified as characteristic for speakers with CSCI. METHODS: Fourteen speech-language pathologists participated in a web-based perceptual task, where their overt reactions to vocal dysfunction were registered during the continuous playback of recordings of 36 speakers (18 with CSCI, and 18 matched controls). Dysphonic events were identified through manual perceptual analysis, to allow the exploration of connections between dysphonic events and listener reactions. RESULTS: More dysphonic events, and more listener reactions, were registered for speakers with CSCI than for noninjured speakers. Strain (particularly in phrase final position) and creak (particularly in nonphrase-final position) distinguish speakers with CSCI from noninjured speakers. CONCLUSIONS: For the identification of intermittent and subtle signs of vocal dysfunction, an approach where the temporal distribution of symptoms is registered offers a viable means to distinguish speakers affected by voice dysfunction from non-affected speakers. In speakers with CSCI, clinicians should listen for presence of final strain and nonfinal creak, and pay attention to self-reported voice function and voice problems, to identify individuals in need for clinical assessment and intervention. PMID- 26850471 TI - Video intervention changes parent perception of all-terrain vehicle (ATV) safety for children. AB - BACKGROUND: Children aged <16 years account for 25% of deaths on all-terrain vehicles (ATVs), despite public health and industry warning against paediatric use. Parents often underestimate instability and other risks associated with ATVs. OBJECTIVE: To determine if a brief intervention consisting of validated computer simulations of ATV performance with a child driver changes attitudes, beliefs and planned safety behaviours of parents of children who ride ATVs. DESIGN/METHODS: Participants were parents of children presenting to a children's hospital emergency department. All participants had children who had ridden an ATV in the past year. Subjects viewed a video simulation of ATVs in scenarios featuring 6-year-old and 10-year-old biofidelic anthropomorphic test devices. Parents completed a survey both before and after viewing the video to report attitudes/beliefs on ATV safety for children, use of safety equipment and family ATV use, as well as risk and safety perception. RESULTS: Surveys were collected from 99 parents, mostly mothers (79%), Caucasian (61%) and had high school education or less (64%). The intervention shifted parents' belief in overall ATV safety (48% unsafe pre-intervention, 73% unsafe post-intervention, p<0.001). After viewing the video simulation, parents were almost six times more likely to perceive ATVs as unsafe (OR 5.96, 95% CI 2.32 to 15.31, p<0.001) and many parents (71%) planned to change family ATV safety rules. CONCLUSION: Video simulations of ATV performance with child riders changed short-term risk perception and planned safety behaviours of parents whose children ride ATVs. Similar educational interventions hold promise for larger-scale studies in at-risk populations. PMID- 26850472 TI - Road traffic injuries in Baghdad from 2003 to 2014: results of a randomised household cluster survey. AB - INTRODUCTION: Around 50 million people are killed or left disabled on the world's roads each year; most are in middle-income cities. In addition to this background risk, Baghdad has been plagued by decades of insecurity that undermine injury prevention strategies. This study aimed to determine death and disability and household consequences of road traffic injuries (RTIs) in postinvasion Baghdad. METHODS: A two-stage, cluster-randomised, community-based household survey was performed in May 2014 to determine the civilian burden of injury from 2003 to 2014 in Baghdad. In addition to questions about household member death, households were interviewed regarding crash specifics, healthcare required, disability, relatedness to conflict and resultant financial hardship. RESULTS: Nine hundred households, totalling 5148 individuals, were interviewed. There were 86 RTIs (16% of all reported injuries) that resulted in 8 deaths (9% of RTIs). Serious RTIs increased in the decade postinvasion and were estimated to be 26 341 in 2013 (350 per 100 000 persons). 53% of RTIs involved pedestrians, motorcyclists or bicyclists. 51% of families directly affected by a RTI reported a significant decline in household income or suffered food insecurity. CONCLUSIONS: RTIs were extremely common and have increased in Baghdad. Young adults, pedestrians, motorcyclists and bicyclists were the most frequently injured or killed by RTCs. There is a large burden of road injury, and the families of road injury victims suffered considerably from lost wages, often resulting in household food insecurity. Ongoing conflict may worsen RTI risk and undermine efforts to reduce road traffic death and disability. PMID- 26850473 TI - Low-intensity pulsed ultrasound induces apoptosis in osteoclasts: Fish scales are a suitable model for the analysis of bone metabolism by ultrasound. AB - Using fish scales in which osteoclasts and osteoblasts coexist on the calcified bone matrix, we examined the effects of low-intensity pulsed ultrasound (LIPUS) on both osteoclasts and osteoblasts. At 3h of incubation after LIPUS treatment, osteoclastic markers such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K mRNA expressions decreased significantly while mRNA expressions of osteoblastic markers, osteocalcin, distal-less homeobox 5, runt-related transcription factor 2a, and runt-related transcription factor 2b, increased significantly. At 6 and 18h of incubation, however, both osteoclastic and osteoblastic marker mRNA expression did not change at least present conditions. Using GeneChip analysis of zebrafish scales treated with LIPUS, we found that cell death-related genes were upregulated with LIPUS treatment. Real-time PCR analysis indicated that the expression of apoptosis-related genes also increased significantly. To confirm the involvement of apoptosis in osteoclasts with LIPUS, osteoclasts were induced by autotransplanting scales in goldfish. Thereafter, the DNA fragmentation associated with apoptosis was detected in osteoclasts using the TUNEL (TdT-mediated dUTP nick end labeling) method. The multi-nuclei of TRAP stained osteoclasts in the scales were labeled with TUNEL. TUNEL staining showed that the number of apoptotic osteoclasts in goldfish scales was significantly elevated by treatment with LIPUS at 3h of incubation. Thus, we are the first to demonstrate that LIPUS directly functions to osteoclasts and to conclude that LIPUS directly causes apoptosis in osteoclasts shortly after exposure. PMID- 26850474 TI - Age Differences in Cancer Treatment Decision Making and Social Support. AB - OBJECTIVE: The aim of this study was to examine the decision-making (DM) styles of younger (18-39 years), middle-aged (40-59 years), and older (>=60 years) cancer survivors, the type and role of social support, and patient satisfaction with cancer treatment DM. METHOD: Adult cancer survivors ( N = 604) were surveyed using Qualtrics online software. RESULTS: Older adults reported significantly lower influence of support on DM than younger adults. The most common DM style for the age groups was collaborative DM with their doctors. Younger age was a significant predictor of independent ( p < .05), collaborative with family ( p < .001), delegated to doctor ( p < .01), delegated to family ( p < .001), and demanding ( p < .001) DM styles. DISCUSSION: Despite having lower received social support in cancer treatment DM, older adults were more satisfied with their DM than younger and middle-aged adults. Health care workers should be aware of different DM styles and influence of social networks to help facilitate optimal patient DM and satisfaction. PMID- 26850475 TI - Angiogenic factor with G patch and FHA domains 1 (Aggf1) regulates liver fibrosis by modulating TGF-beta signaling. AB - Fibrosis is a common pathophysiological process following liver injury and can lead to, if left unattended to, irreversible end-stage liver disease such as cirrhosis. Hepatic stellate cells (HSCs) are a major contributor to liver fibrosis. Here we investigated the involvement of angiogenic factor with G patch and FHA domains 1 (Aggf1) in HSC activation and the underlying mechanisms. Aggf1 expression was down-regulated in the livers in three different mouse models of liver fibrosis following injury. Aggf1 expression was also suppressed in activated HSCs when compared to quiescent HSCs. Over-expression of Aggf1 alleviated liver fibrosis in mice and in cultured HSCs. RNA-sequencing (RNA-seq) analysis performed in HSCs revealed that Aggf1-dependent transcription regulates several key fibrogenic pathways. Mechanistically, Aggf1 regulated liver fibrogenesis by forming a complex with the inhibitor SMAD protein (SMAD7) thereby leading to diminished SMAD3 binding to the pro-fibrogenic gene promoters. On the contrary, SMAD7 knockdown abrogated the effect of Aggf1 and rescued HSC activation. Aggf1 expression was silenced during HSC activation/liver fibrogenesis as a result of DNA methylation. Treatment with a DNA methyltransferase inhibitor (5-Azacytidine) restored Aggf1 expression and repressed liver fibrosis in an Aggf1-dependent manner. In conclusion, our data illustrate a previously unknown role for Aggf1 and shed light on the development of novel therapeutic solutions against liver fibrosis. PMID- 26850476 TI - Enhanced hepatotoxicity by acetaminophen in Vanin-1 knockout mice is associated with deficient proliferative and immune responses. AB - BACKGROUND AND AIMS: Pretreatment with clofibrate, a peroxisome proliferator activated receptor alpha (PPARa) agonist, protects mice from acetaminophen (APAP) injury. Protection is not due to alterations in APAP metabolism and is dependent on PPARa expression. Gene array analysis revealed that mice receiving clofibrate have enhanced hepatic Vanin-1 (Vnn1) gene expression, a response that is also PPARa dependent. METHODS: We examined the role of Vnn1 by comparing the responses of Vnn1 knockout and wild-type mice following APAP hepatotoxicity. APAP metabolism, hepatotoxicity, and compensatory hepatocyte proliferation and immune responses were assessed. RESULTS: Vnn1 knockout mice are more susceptible to APAP hepatotoxicity despite no differences in hepatic glutathione content, gene expression of APAP metabolizing enzymes, or hepatic capacity to bioactivate or detoxify APAP ex vivo. Together, these data strongly suggest that the susceptibility of Vnn1 knockout mice is not due to differences in APAP metabolism. Immunochemistry revealed a lack of proliferating cell nuclear antigen positive hepatocytes and F4/80-positive macrophages in and around areas of centrilobular necrosis in APAP-treated Vnn1 knockouts. Hepatic gene induction of pro-inflammatory cytokines was either significantly reduced or completely blunted in these mice. This was correlated with a reduction in early recruitment of cells positive for granulocyte differentiation antigen 1 or integrin alpha M. Heightened toxicity was also observed in CCl4 and ConA hepatitis models in the absence of Vnn1. CONCLUSIONS: These results indicate that mice lacking Vnn1 have deficiencies in compensatory repair and immune responses following toxic APAP exposure and that these mechanisms may contribute to the enhanced hepatotoxicity seen. PMID- 26850477 TI - Repeated exposure to far infrared ray attenuates acute restraint stress in mice via inhibition of JAK2/STAT3 signaling pathway by induction of glutathione peroxidase-1. AB - Exposure to far-infrared ray (FIR) has been shown to exert beneficial effects on cardiovascular and emotional disorders. However, the precise underlying mechanism mediated by FIR remains undetermined. Since restraint stress induces cardiovascular and emotional disorders, the present study investigated whether exposure to FIR affects acute restraint stress (ARS) in mice. c-Fos immunoreactivity (IR) was significantly increased in the paraventricular hypothalamic nucleus (PVN) and dorsomedial hypothalamic nucleus (DMH) in response to ARS. The increase in c-Fos-IR parallels that in oxidative burdens in the hypothalamus against ARS. Exposure to FIR significantly attenuated increases in the c-Fos-IR, oxidative burdens and corticosterone level. ARS elicited decreases in GSH/GSSG ratio, cytosolic Cu/Zn-superoxide dismutase (SOD-1), glutathione peroxidase (GPx), and glutathione reductase (GR) activities. FIR-mediated attenuation was particularly observed in ARS-induced decrease in GPx, but not in SOD-1 or GR activity. Consistently, ARS-induced decreases in GPx-1 immunoreactivity in PVN and DMH, and decreases in GPx-1 expression in the hypothalamus were significantly attenuated by FIR. ARS-induced significant increases in phosphorylation of JAK2/STAT3, and nuclear translocation and DNA binding activity of NFkappaB were observed in the hypothalamus. Exposure to FIR selectively attenuated phosphorylation of JAK2/STAT3, but did not diminish nuclear translocation and DNA-binding activity of NFkappaB, suggesting that JAK2/STAT3 constitutes a critical target for FIR-mediated pharmacological potential. ARS-induced increase in c-Fos-IR in the PVN and DMH of non-transgenic mice was significantly attenuated by FIR exposure or JAK2/STAT3 inhibitor AG490. GPx-1 overexpressing transgenic mice significantly protected increases in the c Fos-IR and corticosterone level induced by ARS. However, neither FIR exposure nor AG490 significantly affected attenuations by genetic overexpression of GPx-1. Moreover, AG490 did not exhibit any additional positive effects against the attenuation by genetic overexpression of GPx-1 or FIR exposure. Our results indicate that exposure to FIR significantly protects ARS-induced increases in c Fos-IR and oxidative burdens via inhibition of JAK2/STAT3 signaling by induction of GPx-1. PMID- 26850478 TI - Acute blockade of the Caenorhabditis elegans dopamine transporter DAT-1 by the mammalian norepinephrine transporter inhibitor nisoxetine reveals the influence of genetic modifications of dopamine signaling in vivo. AB - Modulation of neurotransmission by the catecholamine dopamine (DA) is conserved across phylogeny. In the nematode Caenorhabditis elegans, excess DA signaling triggers Swimming-Induced Paralysis (Swip), a phenotype first described in animals with loss of function mutations in the presynaptic DA transporter (dat 1). Swip has proven to be a phenotype suitable for the identification of novel dat-1 mutations as well as the identification of novel genes that impact DA signaling. Pharmacological manipulations can also induce Swip, though the reagents employed to date lack specificity and potency, limiting their use in evaluation of dat-1 expression and function. Our lab previously established the mammalian norepinephrine transporter (NET) inhibitor nisoxetine to be a potent antagonist of DA uptake conferred by DAT-1 following heterologous expression. Here we demonstrate the ability of low (MUM) concentrations of nisoxetine to trigger Swip within minutes of incubation, with paralysis dependent on DA release and signaling, and non-additive with Swip triggered by dat-1 deletion. Using nisoxetine in combination with genetic mutations that impact DA release, we further demonstrate the utility of the drug for demonstrating contributions of presynaptic DA receptors and ion channels to Swip. Together, these findings reveal nisoxetine as a powerful reagent for monitoring multiple dimensions of DA signaling in vivo, thus providing a new resource that can be used to evaluate contributions of dat-1 and other genes linked to DA signaling without the potential for compensations that attend constitutive genetic mutations. PMID- 26850480 TI - Re: "The Impact of Insurance Status on Tumor Characteristics...". PMID- 26850479 TI - A next-generation sequencing gene panel (MiamiOtoGenes) for comprehensive analysis of deafness genes. AB - Extreme genetic heterogeneity along with remarkable variation in the distribution of causative variants across in different ethnicities makes single gene testing inefficient for hearing loss. We developed a custom capture/next-generation sequencing gene panel of 146 known deafness genes with a total target size of approximately 1 MB. The genes were identified by searching databases including Hereditary Hearing Loss Homepage, the Human Genome Mutation Database (HGMD), Online Mendelian Inheritance in Man (OMIM) and most recent peer-reviewed publications related to the genetics of deafness. The design covered all coding exons, UTRs and 25 bases of intronic flanking sequences for each exon. To validate our panel, we used 6 positive controls with variants in known deafness genes and 8 unsolved samples from individuals with hearing loss. Mean coverage of the targeted exons was 697X. On average, each sample had 99.8%, 96.2% and 92.7% of the targeted region coverage of 1X, 50X and 100X reads, respectively. Analysis detected all known variants in nuclear genes. These results prove the accuracy and reliability of the custom capture experiment. PMID- 26850481 TI - The Authors Respond. PMID- 26850482 TI - Put Us Out of Business--Please! PMID- 26850483 TI - What Happens When Imatinib Goes Generic? PMID- 26850484 TI - Temporal Heterogeneity of Estrogen Receptor Expression in Bone-Dominant Breast Cancer: 18F-Fluoroestradiol PET Imaging Shows Return of ER Expression. AB - Changes in estrogen receptor (ER) expression over the course of therapy may affect response to endocrine therapy. However, measuring temporal changes in ER expression requires serial biopsies, which are impractical and poorly tolerated by most patients. Functional ER imaging using (18)F-fluoroestradiol (FES)-PET provides a noninvasive measure of regional ER expression and is ideally suited to serial studies. Additionally, lack of measurable FES uptake in metastatic sites of disease predict tumor progression in patients with ER-positive primary tumors treated with endocrine therapy. This report presents a case of restored sensitivity to endocrine therapy in a patient with bone-dominant breast cancer who underwent serial observational FES-PET imaging over the course of several treatments at our center, demonstrating the temporal heterogeneity of regional ER expression. Although loss and restoration of endocrine sensitivity in patients who have undergone prior hormonal and cytotoxic treatments has been reported, this is, to our knowledge, the first time the accompanying changes in ER expression have been documented by molecular imaging. PMID- 26850486 TI - Evaluating the Impact of Provincial Implementation of Screening for Distress on Quality of Life, Symptom Reports, and Psychosocial Well-Being in Patients With Cancer. AB - BACKGROUND: Although a number of accreditation agencies and professional societies recommend routine screening for distress (SFD) for patients with cancer, it has been integrated very slowly into clinical practice. OBJECTIVES: This evaluation investigated the impact of a large-scale SFD intervention on patients' quality of life, symptom reports, and psychosocial well-being. The SFD intervention involved (1) completion of the SFD tool by patients, (2) discussion between patient and provider about the concerns indicated, and (3) provision of appropriate assessments/interventions based on priority concerns. PATIENTS AND METHODS: This quality improvement work included a pre-evaluation and postevaluation of the impact of implementation on patients' well-being. Patients in cohort 1 (N=740) were surveyed before implementation, whereas patients in cohort 2 (N=534) were surveyed 10 months after the implementation at 17 clinics province-wide. As part of the implementation, providers received training on assessing and responding to patient priority concerns with the standardized tool. RESULTS: No differences were seen in total score of quality of life between the cohorts. Fewer patients in cohort 2 than in cohort 1 reported health problems, including tiredness, drowsiness, poor appetite, nausea, anxiety, and poor well being. Similarly, significantly fewer patients in cohort 2 endorsed problems relating to emotional, practical, informational, spiritual, social, and physical aspects of well-being. CONCLUSIONS: Results showed significantly improved psychological and physical symptoms and psychosocial well-being after routine SFD was implemented, suggesting that a large-scale SFD intervention is beneficial for patients when it is integrated into existing clinical practice and community resources. PMID- 26850485 TI - Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2015. AB - The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling and risk assessment and management for hereditary cancer syndromes. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meeting. Major discussion topics this year included multigene testing, risk management recommendations for less common genetic mutations, and salpingectomy for ovarian cancer risk reduction. The panel also discussed revisions to genetic testing criteria that take into account ovarian cancer histology and personal history of pancreatic cancer. PMID- 26850487 TI - A Nomogram to Predict Distant Metastases After Multimodality Therapy for Patients With Localized Esophageal Cancer. AB - BACKGROUND: Among patients with localized esophageal cancer (LEC), 35% or more develop distant metastases (DM) as first relapse, most in the first 24 months after local therapy. Implementation of novel strategies may be possible if DM can be predicted reliably. We hypothesized that clinical variables could help generate a DM nomogram. PATIENTS AND METHODS: Patients with LEC who completed multimodality therapy were analyzed. Various statistical methods were used, including multivariate analysis to generate a nomogram. A concordance index (c index) was established and validated using the bootstrap method. RESULTS: Among 629 patients analyzed (356 trimodality/273 bimodality), 36% patients developed DM as first relapse. The median overall survival from DM was only 8.6 months (95% CI, 7.0-10.2). In a multivariate analysis, the variables associated with a higher risk for developing DM were poorly differentiated histology (hazard ratio [HR], 1.76; P<.0001), baseline T3/T4 primary (HR, 3.07; P=.0006), and baseline N+ LEC (HR, 2.01; P<.0001). Although variables associated with a lower risk for DM were age of 60 years or older (HR, 0.75; P=.04), squamous cell carcinoma (HR, 0.54; P=.013), and trimodality therapy (HR, 0.58; P=.0001), the bias-corrected c-index was 0.67 after 250 bootstrap resamples. CONCLUSIONS: Our nomogram identified patients with LEC who developed DM with a high probability. The model needs to be refined (tumor and blood biomarkers) and validated. This type of model will allow implementation of novel strategies in patients with LEC. PMID- 26850488 TI - The Impact of Electromagnetic Navigational Bronchoscopy on a Multidisciplinary Thoracic Oncology Program. AB - BACKGROUND: The Leo W. Jenkins Cancer Clinic has adopted a programmatic, multidisciplinary approach to thoracic tumors, which has involved the implementation of new therapeutic and diagnostic approaches. In 2012 we began using electromagnetic navigational bronchoscopy (ENB) as a new diagnostic tool. ENB uses a guidance system that combines CT imaging with magnetic field-guided spatial information to allow tissue sampling or placement of fiducial markers to guide radiation therapy. METHODS: The numbers of early-stage (I and II) and late stage (III and IV) lung cancers were compared before and after the introduction of ENB. We also examined the number of cases of fiducial marker placement using bronchoscopy versus interventional radiology before and after ENB was introduced. Fisher's exact test was used to compare the early- versus late-stage lung cancers found at diagnosis pre- and post-ENB introduction, fiducial marker placements using interventional radiology versus bronchoscopy pre- and post-ENB introduction, and pneumothorax rates. RESULTS: More early-stage cancers were diagnosed after ENB introduction (67 of 286 cases vs 116 of 290; P<.0001). Bronchoscopy was also used more frequently to place fiducial markers post-ENB (53 of 86 pre-ENB vs 105 of 117 post-ENB; P<.0001) and had a lower pneumothorax rate (4% vs 22%) than fiducial placement in interventional radiology (P<.001). CONCLUSIONS: The addition of ENB to a multidisciplinary thoracic oncology program may permit the diagnosis of lung cancer at an earlier stage and offers the ability to safely place fiducial markers for therapeutic purposes, such as radiation therapy, within the same procedure, potentially improving safety and decreasing time to treatment. PMID- 26850489 TI - Impact of Prostate Cancer Diagnosis on Noncancer Hospitalizations Among Elderly Medicare Beneficiaries With Incident Prostate Cancer. AB - OBJECTIVES: The purpose of this study was to analyze the impact of cancer diagnosis on noncancer hospitalizations (NCHs) by comparing these hospitalizations between the precancer and postcancer periods in a cohort of fee for-service Medicare beneficiaries with incident prostate cancer. METHODS: A population-based retrospective cohort study was conducted using the SEER-Medicare linked database for 2000 through 2010. The study cohort consisted of 57,489 elderly men (aged >= 67 years) with incident prostate cancer. NCHs were identified in 6 periods (t1-t6) before and after the incidence of prostate cancer. Each period consisted of 120 days. For each period, NCHs were defined as inpatient admissions with primary diagnosis codes not related to prostate cancer, prostate cancer-related procedures, or bowel, sexual, and urinary dysfunction. Bivariate and multivariate comparisons on rates of NCHs between the precancer and postcancer periods accounted for the repeated measures design. RESULTS: The rate of NCHs was higher during the postcancer period (5.1%) compared with the precancer period (3.2%). In both unadjusted and adjusted models, elderly men were 37% (odds ratio [OR], 1.37; 95% CI, 1.32, 1.41) and 38% (adjusted OR, 1.38; 95% CI, 1.33, 1.46) more likely to have any NCHs during the postcancer period compared with the precancer period. CONCLUSIONS: Elderly men with prostate cancer had a significant increase in the risk of NCHs after the diagnosis of prostate cancer. This study highlights the need to design interventions for reducing the excess NCHs after prostate cancer diagnosis among elderly men. PMID- 26850490 TI - Diffuse Large B-Cell Lymphoma Version 1.2016. AB - Diffuse large B-cell lymphomas (DLBCL) are now considered a heterogeneous group of distinct molecular subtypes (germinal center B-cell DLBCL, activated B-cell DLBCL, and primary mediastinal large B-cell lymphoma (PMBL) with varied natural history and response to therapy. In addition, a subset of patients with DLBCL have concurrent MYC and/or BCL2 gene rearrangements (double-hit lymphomas; DHL) and others have a dual expression of both MYC and BCL2 proteins (double expressing DLBCL; DEL). The standard of care for the treatment of patients with PMBL, DHL, or DEL has not been established. Adequate immunophenotyping and molecular testing (in selected circumstances) are necessary for the accurate diagnosis of different subtypes of DLBCL. The NCCN Guidelines included in this issue, part of the NCCN Guidelines for non-Hodgkin's lymphomas, address the diagnosis and management of DLBCL and its subtypes. PMID- 26850491 TI - Real Personalized Medicine. PMID- 26850493 TI - Hypogammaglobulinemia in newly diagnosed chronic lymphocytic leukemia is a predictor of early death. AB - Hypogammaglobulinemia is the most common immune deficiency in chronic lymphocytic leukemia (CLL). However, the prognostic significance in terms of morbidity and mortality remains controversial. We here evaluate the significance of hypogammaglobulinemia in terms of infections, treatment-free survival (TFS), and overall survival (OS). A total of 159 consecutive, newly diagnosed patients were included for analysis. Twenty-five patients (16%) had a moderate or severe infection within one year of diagnosis, but no associations were found between low immunoglobulin (Ig) levels and infections. In multivariate analysis, we found age (>65), high Binet stage, high beta2-microglobulin, and Ig deficiency to be associated with shorter OS. Decreased levels of IgM, deletion of chromosome 17p and unmutated IGHV status had independent negative impact on TFS. Thus, patients with hypogammaglobulinemia did not suffer more from infections early in the disease course, and decreased Ig had independent negative prognostic impact in CLL. PMID- 26850494 TI - Post-Polypectomy Surveillance That Would Please Goldilocks--Not Too Much, Not Too Little, but Just Right. PMID- 26850496 TI - Changes in surface electrocardiogram in patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary endarterectomy. Correlations with hemodynamic and echocardiographic improvements after surgery. AB - BACKGROUND: The aim of the present study was to evaluate the changes of electrocardiographic (ECG) markers of right ventricular (RV) hypertrophy/overload in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary endarterectomy (PEA). METHODS AND RESULTS: We evaluated 99 CTEPH patients who underwent PEA. P wave amplitude in DII, R wave amplitude in V1 and the number of patients with negative T wave in V1-V3 decreased significantly at 1month after surgery with no further change at 1year, in parallel with the rapid improvement in right heart hemodynamics. S wave amplitude in V1, R:S wave ratio in lead V6 and prevalence of SIQIII pattern improved significantly at 1year, in parallel with the progressive reverse remodeling of the right ventricle at echocardiography. CONCLUSIONS: The study shows that some of the ECG markers of RV hypertrophy/overload better reflect RV hemodynamic overload while others better reflect the pathologic remodeling of the right ventricle. PMID- 26850497 TI - Criteria for evaluating rSr' patterns due to high precordial ECG lead placement accurately confirm absence of a Brugada ECG pattern. AB - BACKGROUND: An rSr' pattern in leads V1-V2 can be observed when ECG leads are placed in the 2nd intercostal space. Recently, three criteria analyzing the ST segment and r' width to identify true Brugada pattern ECGs have been described. OBJECTIVES: To assess the feasibility and reliability of using high precordial lead ECGs in conjunction with three new criteria for identifying true Brugada pattern ECGs. METHODS: ECGs of 491 college athletes and 181 non-athletes were performed with standard and high-lead ECGs. ECGs were then analyzed using the newly proposed criteria. RESULTS: Zero patients had a Brugada type 1 or 2 pattern at baseline; 76 patients demonstrated an rSr' pattern in leads V1-V2 on the high lead ECG. Two of the 76 (3%) met criteria suggesting a true Brugada ECG. CONCLUSION: New ECG criteria based on the r' wave accurately identify rSr' patterns in V1-V2 from potential Brugada type 2 patterns in patients with purposely placed high precordial leads. PMID- 26850499 TI - Torsades de pointes after adenosine administration. AB - Adenosine can produce arrhythmias, which are generally short living. It may induce PACs and PVCs, sinus bradycardia, and atrial fibrillation. There have been reports of transient polymorphic VT (torsades de pointes) in patients with LQTS and others in people with normal QT interval. We report a case of a long episode of polymorphic VT induced by adenosine. A 27 year old woman received 6 mg adenosine for PSVT, which terminated and torsades de pointes developed, persisting for 17 seconds and terminated spontaneously. This is the longest described duration of the torsades after adenosine administration in patients with normal QT interval. PMID- 26850495 TI - The MBOAT7-TMC4 Variant rs641738 Increases Risk of Nonalcoholic Fatty Liver Disease in Individuals of European Descent. AB - BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver damage and is characterized by steatosis. Genetic factors increase risk for progressive NAFLD. A genome-wide association study showed that the rs641738 C>T variant in the locus that contains the membrane bound O-acyltransferase domain containing 7 gene (MBOAT7, also called LPIAT1) and transmembrane channel-like 4 gene (TMC4) increased the risk for cirrhosis in alcohol abusers. We investigated whether the MBOAT7-TMC4 is a susceptibility locus for the development and progression of NAFLD. METHODS: We genotyped rs641738 in DNA collected from 3854 participants from the Dallas Heart Study (a multi-ethnic population-based probability sample of Dallas County residents) and 1149 European individuals from the Liver Biopsy Cross-Sectional Cohort. Clinical and anthropometric data were collected, and biochemical and lipidomics were measured in plasma samples from participants. A total of 2736 participants from the Dallas Heart Study also underwent proton magnetic resonance spectroscopy to measure hepatic triglyceride content. In the Liver Biopsy Cross-Sectional Cohort, a total of 1149 individuals underwent liver biopsy to diagnose liver disease and disease severity. RESULTS: The genotype rs641738 at the MBOAT7-TMC4 locus associated with increased hepatic fat content in the 2 cohorts, and with more severe liver damage and increased risk of fibrosis compared with subjects without the variant. MBOAT7, but not TMC4, was found to be highly expressed in the liver. The MBOAT7 rs641738 T allele was associated with lower protein expression in the liver and changes in plasma phosphatidylinositol species consistent with decreased MBOAT7 function. CONCLUSIONS: We provide evidence for an association between the MBOAT7 rs641738 variant and the development and severity of NAFLD in individuals of European descent. This association seems to be mediated by changes in the hepatic phosphatidylinositol acyl-chain remodeling. PMID- 26850498 TI - How to Review a Manuscript. AB - Manuscript peer review is fundamental to the evaluation and dissemination of modern science; it is the process whereby good science is enhanced and bad science is dismissed. Very little objective evidence, however, has been amassed to guide the manuscript peer review process. Rather, it is learned by experience and mentoring: by doing reviews, receiving reviews of one's own work, and by obtaining feedback from seasoned reviewers. Here, I lay out my perspective on this cornerstone of the scientific endeavor. PMID- 26850500 TI - First report of a mecA-positive multidrug-resistant Staphylococcus pseudintermedius isolated from a dog in New Zealand. AB - CASE HISTORY: A 14-year-old neutered male Sealyham terrier was referred for assessment of a persistent pyoderma. It had experienced numerous episodes of dermatitis involving pododermatitis, pyoderma and otitis over the previous 6 years. CLINICAL FINDINGS: Superficial, focally deep and mucocutaneous pyoderma were present, with yellow mucoid exudate on both nares and the lower lips crusted with haemopurulent exudate. Epidermal collarettes were present on the dorsal and lateral trunk. There were peri-anal crusts and mild erythema was present on the concave aspect of both pinnae. MICROBIOLOGICAL FINDINGS: Culture and microbiological testing identified Staphylococcus pseudintermedius as the infecting organism. Kirby-Bauer disc susceptibility testing revealed the isolate was resistant to numerous antimicrobials including oxacillin. PCR testing of the isolate identified the presence of the mecA gene which confers resistance to beta lactam antimicrobials. Pulsed field gel electrophoresis typing suggested the isolate was not related to the methicillin-resistant S. pseudintermedius that had been reported to be associated with canine infections in Western Australia. DIAGNOSIS: Superficial, deep and mucus membrane pyoderma associated with a multi drug resistant S. pseudintermedius. CLINICAL RELEVANCE: This is the first recorded case of canine pyoderma involving methicillin-resistant multidrug resistant S. pseudintermedius in New Zealand. Treatment of such cases is difficult because the number of effective and available antimicrobials is limited. This finding should raise the awareness of the veterinary and medical professions to the presence of such organisms in New Zealand and stimulate a discussion about possible biosecurity barriers, treatment strategies and prevention of zoonotic and nosocomial infections. PMID- 26850501 TI - [Cultural adaptation to Spanish and assessment of an Adolescent Peer Relationships Tool for detecting school bullying: Preliminary study of the psychometric properties]. AB - BACKGROUND AND OBJECTIVES: School bullying is a growing problem. The current study is aimed at culturally adapting and assessing the psychometric properties of a brief scale to measure bullying. MATERIAL AND METHODS: A cross-cultural adaptation of the brief scale -Adolescent Peer Relations Instrument-Bullying (APRI)- was performed using the translation and back-translation technique. The Spanish version of APRI questionnaire was administered to a sample of 1,428 schoolchildren aged 12-14years in the region of Mar Menor in Murcia (Spain). Exploratory factor analysis, with oblique rotation, was used to assess the validity of the internal structure, the Cronbach's alpha to analyse their consistency, and the Kruskal-Wallis test to check their ability to discriminate between subjects with varying degrees of bullying according to Kidscreen-52 scale of social acceptability RESULTS: Two factors were identified in the adapted version of APRI (physical victimisation and verbal/social victimisation), similar to those in the original scale. The questionnaire has high internal consistency (Cronbach's alpha=0.94) and discrimination capacity (P<01), with significant effect sizes between degrees of bullying. CONCLUSIONS: The internal structure of the APRI Spanish version is similar to the original, and its scores confirm high reliability and construct validity. Further studies need to be performed with broader age ranges and confirmatory analysis techniques, to ratify the equivalence of the adapted version with the original version. PMID- 26850502 TI - Focal cortical dysplasia and heterochromia of the iris. PMID- 26850503 TI - Cardiac manifestations in alcoholic liver disease. AB - Alcoholic liver disease is the most prevalent cause of progressive liver disease in Europe. Alcoholic cirrhosis occurs in 8%-20% of cases of alcoholic liver disease. It has significant influence on cardiovascular system and haemodynamics through increased heart rate, cardiac output, decreased systemic vascular resistance, arterial pressure and plasma volume expansion. Cirrhotic cardiomyopathy is characterised by systolic and diastolic dysfunction and electrophysiological abnormalities, if no other underlying cardiac disease is present. It is often unmasked only during pharmacological or physiological stress, when compensatory mechanisms of the heart become insufficient to maintain adequate cardiac output. Low-to-moderate intake of alcohol can be cardioprotective. However, heavy drinking is associated with an increased risk of cardiovascular diseases, such as alcoholic cardiomyopathy, arterial hypertension, atrial arrhythmias as well as haemorrhagic and ischaemic stroke. Alcoholic cardiomyopathy is characterised by dilated left ventricle (LV), increased LV mass, normal or reduced LV wall thickness and systolic dysfunction. PMID- 26850504 TI - Continuing medical education for general practitioners: a practice format. AB - INTRODUCTION: Our current knowledge-based society and the many actualisations within the medical profession require a great responsibility of physicians to continuously develop and refine their skills. In this article, we reflect on some recent findings in the field of continuing education for professional doctors (continuing medical education, CME). Second, we describe the development of a CME from the Academic Center for General Practice (ACHG) of the KU Leuven. METHODS: First, we performed a literature study and we used unpublished data of a need assessment performed (2013) in a selected group of general practitioners. Second, we describe the development of a proposal to establish a CME programme for general practitioners. RESULTS: CME should go beyond the sheer acquisition of knowledge, and also seek changes in practice, attitudes and behaviours of physicians. The continuing education offerings are subject to the goals of the organising institution, but even more to the needs and desires of the end user. CONCLUSIONS: Integrated education is crucial to meet the conditions for efficient and effective continuing education. The ACHG KU Leuven decided to offer a postgraduate programme consisting of a combination of teaching methods: online courses (self-study), contact courses (traditional method) and a materials database. PMID- 26850506 TI - [Pediatric optic nerve sheath meningioma with intraocular extension]. PMID- 26850505 TI - The multivariate association between genomewide DNA methylation and climate across the range of Arabidopsis thaliana. AB - Epigenetic changes can occur due to extracellular environmental conditions. Consequently, epigenetic mechanisms can play an intermediate role to translate environmental signals to intracellular changes. Such a role might be particularly important in plants, which often show strong local adaptation and have the potential for heritable epigenetic states. However, little is currently known about the role of epigenetic variation in the ecological mechanisms of adaptation. Here, we used multivariate redundancy analyses to examine genomewide associations between DNA methylation polymorphisms and climate variation in two independent panels of Arabidopsis accessions, including 122 Eurasian accessions as well as in a regional panel of 148 accessions in Sweden. At the single nucleotide methylation level, climate and space (geographic spatial structure) explain small yet significant amount of variation in both panels. On the other hand, when viewed in a context of genomic clusters of methylated and unmethylated cytosines, climate and space variables explain much greater amounts of variation in DNA methylation than those explained by variation at the single-nucleotide level. We found that the single-nucleotide methylation polymorphisms with the strongest associations with climate were enriched in transposable elements and in potentially RNA-directed methylation contexts. When viewed in the context of genomic clusters, variation of DNA methylation at different sequence contexts exhibit distinctive segregation along different axes of variation in the redundancy analyses. Genomewide methylation showed much stronger associations with climate within the regional panel (Sweden) compared to the global (Eurasia). Together, these findings indicate that genetic and epigenetic variation across the genome may play a role in response to climate conditions and local adaptation. PMID- 26850507 TI - Tuberculous ischemic panvasculitis: An ophthalmological challenge. PMID- 26850508 TI - [Treatment with ranibizumab for choroidal neovascularization secondary to a pseudoxanthoma elasticum: Results of the French observational study PiXEL]. AB - INTRODUCTION: Pseudoxanthoma elasticum (PXE), a rare hereditary connective tissue disorder, may be complicated by angioid streaks (AS) and choroidal neovascularization (CNV), which may lead to irreversible loss of visual acuity (VA). Here we describe the safety and efficacy of ranibizumab in patients with CNV secondary to PXE. METHODS: A multicenter (n=23), observational study of a retrospective/prospective cohort, performed under real world conditions in France in all patients with CNV secondary to PXE who received at least one ranibizumab injection as of October 2011. The study objectives were to describe the mean annual number and reason for ranibizumab injections since initiation, evolution of best-corrected visual acuity (BCVA by Early Treatment Diabetic Retinopathy Study [ETDRS] letters), and safety. RESULTS: Patients (n=72; 98 eyes) had a mean age of 59.6+/-8.3years and consisted of 54.2% men. The criterion for retreatment was based mainly on loss of VA, progression of CNV and angiographic leakage. CNV was primarily subfoveal or juxtafoveal (73.4%), and the initial mean VA was 64.6 ETDRS letters. On average, visual acuity of all eyes analyzed was relatively stable during the 2-year follow-up (62.3 letters vs 64.6 letters at the first injection), and 88.6% of eyes maintained VA between -15 and +15 letters or gained over 15 letters. No deaths or new intolerances were described. CONCLUSIONS: These results showed that ranibizumab was able to maintain stable VA in clinical practice for at least 2years in patients with CNV secondary to PXE, and to significantly reduce the frequency of neovascularization relapses, with a limited number of injections. The treatment was well tolerated by the patients. PMID- 26850509 TI - Pre- and post-natal growth in two sisters with 3-M syndrome. AB - 3-M syndrome (OMIM #273750) is a rare autosomal recessive growth disorder characterized by severe pre- and post-natal growth restriction, associated with minor skeletal abnormalities and dysmorphisms. Although the 3-M syndrome is well known as a primordial dwarfism, descriptions of the prenatal growth are missing. We report a family with variable phenotypic features of 3-M syndrome and we describe the prenatal and postnatal growth pattern of two affected sisters with a novel homozygous CUL7 mutation (c.3173-1G>C), showing a pre- and post-natal growth deficiency and a normal cranial circumference. PMID- 26850510 TI - A 10-year study of factors associated with alcohol treatment use and non-use in a U.S. population sample. AB - BACKGROUND: This study seeks to identify changes in perceived barriers to alcohol treatment and predictors of treatment use between 1991-92 and 2001-02, to potentially help understand reported reductions in treatment use at this time. Social, economic, and health trends during these 10 years provide a context for the study. METHODS: Subjects were Whites, Blacks, and Hispanics. The data were from the National Longitudinal Alcohol Epidemiologic Survey (NLAES) and the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). We conducted two analyses that compared the surveys on: (1) perceived treatment barriers for subjects who thought they should get help for their drinking, and (2) variables predicting past-year treatment use in an alcohol use disorder subsample using a multi-group multivariate regression model. RESULTS: In the first analysis, those barriers that reflected negative beliefs and fears about seeking treatment as well as perceptions about the lack of need for treatment were more prevalent in 2001-02. The second analysis showed that survey year moderated the relationship between public insurance coverage and treatment use. This relationship was not statistically significant in 1991-92 but was significant and positive in 2001-02, although the effect of this change on treatment use was small. CONCLUSIONS: Use of alcohol treatment in the U.S. may be affected by a number of factors, such as trends in public knowledge about treatment, social pressures to reduce drinking, and changes in the public financing of treatment. PMID- 26850511 TI - Validity of the CAGE questionnaire for men who have sex with men (MSM) in China. AB - BACKGROUND: Detection of heavy drinking among men who have sex with men (MSM) is crucial for both intervention and treatment. The CAGE questionnaire is a popular screening instrument for alcohol use problems. However, the validity of CAGE for Chinese MSM is unknown. METHOD: Data were from three waves of cross-sectional assessments among general MSM (n=523) and men who sell sex to other men ("money boys" or MBs, n=486) in Shanghai, China. Specifically, participants were recruited using respondent-driven, community popular opinion leader, and venue based sampling methods. The validity of the CAGE was examined for different cutoff scores and individual CAGE items using self-reported heavy drinking (>=14 drinks in the past week) as a criterion. RESULTS: In the full sample, 75 (7.4%) of participants were classified as heavy drinkers. 32 (6.1%) of general MSM and 43 (8.9%) of MBs were heavy drinkers. The area under curve statistics for overall sample was 0.7 (95% CI: 0.36-0.77). Overall, the sensitivities (ranging from 18.7 to 66.7%), specificities (ranging from 67.5 to 95.8%), and positive predictive values (ranging from 14.1 to 26.4%) for different cutoff scores were inadequate using past week heavy drinking as the criterion. The ability of CAGE to discriminate heavy drinkers from non-heavy drinkers was limited. CONCLUSIONS: Our findings showed the inadequate validity of CAGE as a screening instrument for current heavy drinking in Chinese MSM. Further research using a combination of validity criteria is needed to determine the applicability of CAGE for this population. PMID- 26850513 TI - Asymptomatic elite young tennis players show lateral and ventral growth plate alterations of proximal humerus on MRI. AB - PURPOSE: The specific aim of the study was to investigate and compare epiphyseal length and extension in the proximal humerus, closure in the growth plate and bone marrow signal intensity related to the proximal humeral physis in the dominant arm and the non-dominant arm of the asymptomatic adolescent elite tennis player. METHODS: The study sample included 35 asymptomatic elite young tennis players (15 males and 20 females, mean age 17.4 years +/- 2.7). Each player contributed with two shoulders to the MRI measurement. The non-dominant arm was used as a control. RESULTS: Relative reliability between the radiologists was excellent (ICC 0.78-0.96). Statistically significant differences between dominant arm and non-dominant arm in epiphyseal length (mm) laterally (DA 27.3 vs NDA 26.7) were shown. Statistically significant differences were also found in epiphyseal extension (mm) laterally (DA 36.1 vs NDA 35.1) and ventrally (DA 36.2 vs NDA 34.8). No statistically significant differences were found between dominant arm and non-dominant arm in epiphyseal extension (mm) medially (DA 31.7 vs NDA 31.7) and dorsally (DA 22.6 vs NDA 22.1). CONCLUSIONS: Significant findings assessing MRI measurements of the epiphyseal plate in the asymptomatic adolescent elite tennis player might reflect a development of consecutive alterations in the epiphyseal plate in the dominant arm. LEVEL OF EVIDENCE: Diagnostic study, Level IV. PMID- 26850512 TI - Measuring specific receptor binding of a PET radioligand in human brain without pharmacological blockade: The genomic plot. AB - PET studies allow in vivo imaging of the density of brain receptor species. The PET signal, however, is the sum of the fraction of radioligand that is specifically bound to the target receptor and the non-displaceable fraction (i.e. the non-specifically bound radioligand plus the free ligand in tissue). Therefore, measuring the non-displaceable fraction, which is generally assumed to be constant across the brain, is a necessary step to obtain regional estimates of the specific fractions. The nondisplaceable binding can be directly measured if a reference region, i.e. a region devoid of any specific binding, is available. Many receptors are however widely expressed across the brain, and a true reference region is rarely available. In these cases, the nonspecific binding can be obtained after competitive pharmacological blockade, which is often contraindicated in humans. In this work we introduce the genomic plot for estimating the nondisplaceable fraction using baseline scans only. The genomic plot is a transformation of the Lassen graphical method in which the brain maps of mRNA transcripts of the target receptor obtained from the Allen brain atlas are used as a surrogate measure of the specific binding. Thus, the genomic plot allows the calculation of the specific and nondisplaceable components of radioligand uptake without the need of pharmacological blockade. We first assessed the statistical properties of the method with computer simulations. Then we sought ground-truth validation using human PET datasets of seven different neuroreceptor radioligands, where nonspecific fractions were either obtained separately using drug displacement or available from a true reference region. The population nondisplaceable fractions estimated by the genomic plot were very close to those measured by actual human blocking studies (mean relative difference between 2% and 7%). However, these estimates were valid only when mRNA expressions were predictive of protein levels (i.e. there were no significant post-transcriptional changes). This condition can be readily established a priori by assessing the correlation between PET and mRNA expression. PMID- 26850514 TI - Arthroscopic modified Mason-Allen technique for large U- or L-shaped rotator cuff tears. AB - PURPOSE: While a conventional single- or double-row repair technique could be applied for repair of C-shaped tears, a different surgical strategy should be considered for repair of U- or L-shaped tears because they typically have complex patterns with anterior, posterior, or both mobile leaves. This study was performed to examine the outcomes of the modified Mason-Allen technique for footprint restoration in the treatment of large U- or L-shaped rotator cuff tears. METHODS: Thirty-two patients who underwent an arthroscopic modified Mason Allen technique for large U- or L-shaped rotator cuff tears between January 2012 and December 2013 were included in this study. Margin convergence was first performed to reduce the tear gap and tension, and then, an arthroscopic Mason Allen technique was performed to restore the rotator cuff footprint in a side-to end repair fashion. All patients were evaluated preoperatively and for a minimum of 2 years of follow-up with a visual analog scale (VAS) for pain, Constant score, and ultrasonography. RESULTS: There was significant improvement in all VAS and Constant scores compared with the preoperative values (P < 0.001). Functional results by Constant scores included 9 cases that were classified as excellent, 11 cases as good, 8 cases as fair, and 2 cases as poor. Binary logistic regression analysis revealed that heavy work, pseudoparalysis, joint space narrowing, fatty degeneration of the SST and IST, and a positive tangent sign were found to significantly correlate with functional outcomes. Multivariable logistic regression analysis revealed that only fatty degeneration of the SST was a risk factor for fair/poor clinical outcomes. Complications occurred in 5 of the 32 patients (15.6 %), and the reoperation rate due to complications was 6.3 % (2 of 32 patients). CONCLUSIONS: An arthroscopic modified Mason-Allen technique was sufficient to restore the footprint of the rotator cuff in our data. Overall satisfactory results were achieved in most patients, with the exception of those with severe fatty degeneration. An arthroscopic modified Mason-Allen technique could be an effective and reliable alternative for patients with large U- or L shaped rotator cuff tears. LEVEL OF EVIDENCE: Case Series, Therapeutic Level IV. PMID- 26850515 TI - Patients' perceptions of repair, rehabilitation and recovery after major orthopaedic trauma: a qualitative study. AB - INTRODUCTION: The most common major trauma injuries are multiple fractures. Orthopaedic trauma research has traditionally focused on surgical techniques, and the impact of this major life event on the patient is not well understood. This study explored how patients make sense of their rehabilitation and recovery following major orthopaedic trauma. DESIGN: Qualitative study using an Interpretative Phenomenological Analysis approach. METHODS: Semi-structured interviews of a purposive sample of 15 patients 3 to 6 months after sustaining major orthopaedic injuries, treated at a major trauma centre in England. FINDINGS: Recovery after trauma was conceptualised as a journey through repair and rehabilitation to achieve recovery. These phases were represented by three superordinate themes: getting back on your feet, getting the right help to get there, and regaining a sense of normality. Participants considered orthopaedic consultants and physiotherapists to be the primary professionals to provide the tools to enable them to help themselves. Improving physical function helped to restore emotional well-being, with recovery only attained when participants had normalised a new sense of self, and regained confidence or enjoyment in their chosen activities. CONCLUSION: Rehabilitation is a complex process of coming to terms with physical and social limitations to normalise a new sense of self. Individuals considered rehabilitation to be their responsibility; however, they needed expert help to know what to do. Physiotherapists were key to getting people back on their feet, and by facilitating physical recovery, physiotherapists were able to have a positive impact on emotional well-being. PMID- 26850516 TI - Concise Review: Heteroplasmic Mitochondrial DNA Mutations and Mitochondrial Diseases: Toward iPSC-Based Disease Modeling, Drug Discovery, and Regenerative Therapeutics. AB - Mitochondria contain multiple copies of their own genome (mitochondrial DNA; mtDNA). Once mitochondria are damaged by mutant mtDNA, mitochondrial dysfunction is strongly induced, followed by symptomatic appearance of mitochondrial diseases. Major genetic causes of mitochondrial diseases are defects in mtDNA, and the others are defects of mitochondria-associating genes that are encoded in nuclear DNA (nDNA). Numerous pathogenic mutations responsible for various types of mitochondrial diseases have been identified in mtDNA; however, it remains uncertain why mitochondrial diseases present a wide variety of clinical spectrum even among patients carrying the same mtDNA mutations (e.g., variations in age of onset, in affected tissues and organs, or in disease progression and phenotypic severity). Disease-relevant induced pluripotent stem cells (iPSCs) derived from mitochondrial disease patients have therefore opened new avenues for understanding the definitive genotype-phenotype relationship of affected tissues and organs in various types of mitochondrial diseases triggered by mtDNA mutations. In this concise review, we briefly summarize several recent approaches using patient-derived iPSCs and their derivatives carrying various mtDNA mutations for applications in human mitochondrial disease modeling, drug discovery, and future regenerative therapeutics. PMID- 26850517 TI - Recurrence of ANCA-associated vasculitis in a patient with kidney trasplant. AB - Renal disease secondary to vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA) can lead to chronic renal disease requiring renal replacement therapy. In these patients, kidney transplantation offers excellent long-term rates of allograft and patient survival; consequently, they can be trasplanted when the clinical disease activity has remitted. However, the risk of disease relapses in the renal allograft remains, although at lower rates due to modern immunosuppressive regimens. We describe the case of a male patient with extracapillary glomerulonephritis type III C-ANCA (+) who developed a recurrence in the renal allograft 8 years after transplantation. Intensive immunosupression with plasmapheresis controlled the disease. PMID- 26850519 TI - Engorged myometrial vein sign in uterine torsion. PMID- 26850520 TI - From the Editor. PMID- 26850521 TI - Controversies in hypertension: rationale and approach. PMID- 26850518 TI - Enhancing the evaluation of PI3K inhibitors through 3D melanoma models. AB - Targeted therapies for mutant BRAF metastatic melanoma are effective but not curative due to acquisition of resistance. PI3K signaling is a common mediator of therapy resistance in melanoma; thus, the need for effective PI3K inhibitors is critical. However, testing PI3K inhibitors in adherent cultures is not always reflective of their potential in vivo. To emphasize this, we compared PI3K inhibitors of different specificity in two- and three-dimensional (2D, 3D) melanoma models and show that drug response predictions gain from evaluation using 3D models. Our results in 3D demonstrate the anti-invasive potential of PI3K inhibitors and that drugs such as PX-866 have beneficial activity in physiological models alone and when combined with BRAF inhibition. These assays finally help highlight pathway effectors that could be involved in drug response in different environments (e.g. p4E-BP1). Our findings show the advantages of 3D melanoma models to enhance our understanding of PI3K inhibitors. PMID- 26850522 TI - Age matters in the treatment and management of hypertension. PMID- 26850523 TI - Age should not be a primary consideration in the management of hypertension. PMID- 26850525 TI - Can metabolic control variables of diabetic patients predict their quality of life? AB - The type and the complexity of regimen aimed at achieving better glycemic control may impact patient's health-related quality of life (HRQoL) in diabetic patients. But, the relationship between HbA1c levels of diabetic patients and their HRQoL is not clear. Our study aims to determine whether metabolic control variables can predict HRQoL or not and also the impact of hypertension (HT) on HRQoL in type II diabetic patients. A total of 469 patients with type II diabetes and 134 control subjects were studied. Medical Outcomes Study Short-Form-General Health Survey (SF-36) questionnaire was used as a health survey tool to measure the QoL of patients in the study. SF-36 includes 8 individual subscales and two summary scales (physical component summary [PCS] and mental component summary [MCS]). Age, gender, fasting blood glucose, postprandial blood glucose, HbA1c, high density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL C), triglyceride, total cholesterol, Apolipoprotein B (apoB), non-HDL-C, and body mass index values of the subjects were recorded. For statistical evaluation, SPSS (Statistical Package for the Social Sciences) 15 under Windows 7 was used. MCS values of patients group were statistically lower than control group (P < .05). There was no significant difference in PCS values between groups (P > .05). Diabetic patients with HT had significantly lower PCS and MCS values than those without HT. In addition, there was a negative correlation between HbA1c level and PCS and MCS values (P < .05). Hypertensive diabetic patients had significantly higher fasting blood glucose, postprandial blood glucose, HbA1c, HDL-C, LDL-C, total cholesterol, and body mass index values than hypertensive control subjects (P < .05). Normotensive diabetic patients also had significantly lower PCS value than normotensive control subjects (P < .05). But, MCS value was not different between groups (P > .05). PCS values in diabetic male patients were significantly higher than in diabetic female patients (P < .05). MCS value did not differ by gender in diabetic patients (P > .05). In our study, it is clear that diabetes affected the patients' HRQoL. In addition, we showed negative correlations between HbA1c levels and PCS and MCS values. There was a significant difference in PCS scores between genders in patients with diabetes. But, there was no significant difference in PCS and MCS values by age in diabetic patients. And having concomitant HT in diabetic patients causes a decrease in both MCS and PCS scores. Thus, HT is an important factor that should be considered in QoL of the diabetic patients. PMID- 26850524 TI - The septal bulge--an early echocardiographic sign in hypertensive heart disease. AB - Patients in the early stage of hypertensive heart disease tend to have normal echocardiographic findings. The aim of this study was to investigate whether pathology-specific echocardiographic morphologic and functional parameters can help to detect subclinical hypertensive heart disease. One hundred ten consecutive patients without a history and medication for arterial hypertension (AH) or other cardiac diseases were enrolled. Standard echocardiography and two dimensional speckle-tracking-imaging analysis were performed. Resting blood pressure (BP) measurement, cycle ergometer test (CET), and 24-hour ambulatory BP monitoring (ABPM) were conducted. Patients were referred to "septal bulge (SB)" group (basal-septal wall thickness >= 2 mm thicker than mid-septal wall thickness) or "no-SB" group. Echocardiographic SB was found in 48 (43.6%) of 110 patients. In this SB group, 38 (79.2%) patients showed AH either by CET or ABPM. In contrast, in the no-SB group (n = 62), 59 (95.2%) patients had no positive test for AH by CET or ABPM. When AH was solely defined by resting BP, SB was a reasonable predictive sign for AH (sensitivity 73%, specificity 76%). However, when AH was confirmed by CET or ABPM the echocardiographic SB strongly predicted clinical AH (sensitivity 93%, specificity 86%). In addition, regional myocardial deformation of the basal-septum in SB group was significantly lower than in no-SB group (14 +/- 4% vs. 17 +/- 4%; P < .001). In conclusion, SB is a morphologic echocardiographic sign for early hypertensive heart disease. Sophisticated BP evaluation including resting BP, ABPM, and CET should be performed in all patients with an accidental finding of a SB in echocardiography. PMID- 26850526 TI - In vitro and in vivo effects of lutein against cisplatin-induced ototoxicity. AB - INTRODUCTION: Cisplatin is a commonly prescribed drug that produces ototoxicity as a side effect. Lutein is a carotenoid with antioxidant and anti-inflammatory properties previously tested for eye, heart and skin diseases but not evaluated to date in ear diseases. AIM: To evaluate the protective effects of lutein on HEI OC1 auditory cell line and in a Wistar rat model of cisplatin ototoxicity. MATERIALS AND METHODS: In vitro study: Culture HEI-OC1 cells were exposed to lutein (2.5-100 MUM) and to 25 MUM cisplatin for 24h. In vivo study: Twenty eight female Wistar rats were randomized into three groups. Group A (n=8) received intratympanic lutein (0.03 mL) (1mg/mL) in the right ear and saline solution in the left one to determine the toxicity of lutein. Group B (n=8) received also intraperitoneal cisplatin (10mg/kg) to test the efficacy of lutein against cisplatin ototoxicity. Group C (n=12) received intratympanic lutein (0.03 mL) (1mg/mL) to quantify lutein in cochlear fluids (30 min, 1h and 5 days after treatment). Hearing function was evaluated by means of Auditory Steady-State Responses before the procedure and 5 days after (groups A and B). Morphological changes were studied by confocal laser scanning microscopy. RESULTS: In vitro study: Lutein significantly reduced the cisplatin-induced cytotoxicity in the HEI OC1 cells when they were pre-treated with lutein concentrations of 60 and 80 MUM. In vivo study: Intratympanic lutein (1mg/mL) application showed no ototoxic effects. However it did not achieve protective effect against cisplatin-induced ototoxicity in Wistar rats. CONCLUSIONS: Although lutein has shown beneficial effects in other pathologies, the present study only obtained protection against cisplatin ototoxicity in culture cells, but not in the in vivo model. The large molecule size, the low dose administered, and restriction to diffusion in the inner ear could account for this negative result. PMID- 26850527 TI - The Matrix Metalloproteinase 9 Point-of-Care Test in Dry Eye. AB - Dry eye is a common, multifactorial disease currently diagnosed by a combination of symptoms and signs. However, the subjective symptoms of dry eye poorly correlate to the current gold standard for diagnostic tests, reflecting the need to develop better objective tests for the diagnosis of dry eye. This review considers the role of ocular surface matrix metalloproteinase 9 (MMP-9) in dry eye and the implications of a novel point-of-care test that measures MMP-9 levels, InflammaDry (RPS, Sarasota, FL) on choosing appropriate therapeutic treatments. PMID- 26850529 TI - X and Y chromosome-bearing spermatozoa are equally able to uptake and internalize exogenous DNA by sperm-mediated gene transfer in swine. AB - Since proteomic differences between male X/Y chromosome-bearing gametes have recently been described, a question has been raised: could these differences be responsible for different behavior between X and Y chromosome-bearing spermatozoa during the binding and internalization of exogenous DNA in the swine species? In order to investigate this hypothesis, our group studied the process of the uptake and internalization of exogenous DNA in X and Y chromosome-bearing sperm sub populations. No significant differences were found between sperm types in both the uptake and internalization of exogenous DNA. The quantity of internalized exogenous DNA was significantly lower than that of the uptaken DNA. In conclusion, our results showed that X and Y chromosomes-bearing spermatozoa have the same binding capacity and internalization of DNA, and the proteomic differences between them do not seem to interfere with these complex processes. PMID- 26850528 TI - Neural Mechanisms Behind Identification of Leptokurtic Noise and Adaptive Behavioral Response. AB - Large-scale human interaction through, for example, financial markets causes ceaseless random changes in outcome variability, producing frequent and salient outliers that render the outcome distribution more peaked than the Gaussian distribution, and with longer tails. Here, we study how humans cope with this evolutionary novel leptokurtic noise, focusing on the neurobiological mechanisms that allow the brain, 1) to recognize the outliers as noise and 2) to regulate the control necessary for adaptive response. We used functional magnetic resonance imaging, while participants tracked a target whose movements were affected by leptokurtic noise. After initial overreaction and insufficient subsequent correction, participants improved performance significantly. Yet, persistently long reaction times pointed to continued need for vigilance and control. We ran a contrasting treatment where outliers reflected permanent moves of the target, as in traditional mean-shift paradigms. Importantly, outliers were equally frequent and salient. There, control was superior and reaction time was faster. We present a novel reinforcement learning model that fits observed choices better than the Bayes-optimal model. Only anterior insula discriminated between the 2 types of outliers. In both treatments, outliers initially activated an extensive bottom-up attention and belief network, followed by sustained engagement of the fronto-parietal control network. PMID- 26850530 TI - Caspase-9 inhibitor Z-LEHD-FMK enhances the yield of in vitro produced buffalo (Bubalus bubalis) pre-implantation embryos and alters cellular stress response. AB - The present investigation was done to study the effect of caspase-9 inhibitor Z LEHD-FMK, on in vitro produced buffalo embryos. Z-LEHD-FMK is a cell-permeable, competitive and irreversible inhibitor of enzyme caspase-9, which helps in cell survival. Buffalo ovaries were collected from slaughterhouse and the oocytes were subjected to in vitro maturation (IVM), in vitro fertilization (IVF) and in vitro culture (IVC). The culture medium was supplemented with Z-LEHD-FMK at different concentrations i.e. 0 MUM (control), 10 MUM, 20 MUM, 30 MUM and 50 MUM during IVM and IVC respectively. After day-2 post-insemination, the cleavage rate was significantly higher (74.20 +/- 5.87% at P<0.05) in the group treated with 20 MUM of Z-LEHD-FMK than at any other concentration. Same trend was observed in the blastocyst production rate which was higher at 20 MUM (27.42 +/- 2.94% at P<0.05). The blastocysts obtained at day-8 of the culture at different concentrations were subjected to TUNEL assay, to determine the level of apoptosis during the culture medium supplied with 20 MUM Z-LEHD-FMK which showed apoptotic index significantly lower (1.88 +/- 0.87 at P<0.05). There was a non-significant increase in total cell number in all Z-LEHD-FMK treated blastocysts. The quantitative gene expression of CHOP and HSP10 genes showed significant increase (P<0.05) in the group treated with 50 MUM Z-LEHD-FMK, while, HSP40 showed significant increase (P<0.05) at 30 MUM and 50 MUM Z-LEHD-FMK concentrations. From the afore mentioned results we conclude that, Z-LEHD-FMK at 20 MUM increased the cleavage and blastocyst rate of buffalo pre-implantation embryos also affecting the rate of apoptosis and cellular stress at various concentrations. PMID- 26850531 TI - Immunohistochemical analysis of the hypothalamic-pituitary-adrenal axis in dogs: Sex-linked and seasonal variation. AB - This study evaluated sexual dimorphism and seasonal variations in corticotrophs and adrenal zona fasciculata in dogs, as well as the expression of oestrogen receptor alpha (ERalpha). An immunohistochemical analysis was conducted in pituitaries for ACTH and in adrenal glands for ERalpha and for the melanocortin-2 receptor (MC2R) in winter and summer. Double immunofluorescence was performed to identify ERalpha in corticotrophs. Females had a greater proportion of corticotrophs per field (p<0.01), with a greater cellular area and optical density (p<0.001) than males. Optical density of corticotrophs was greater in winter for both sexes (p<0.001). In zona fasciculata, ERalpha and MC2R expression was greater in females (p<0.001) and was greater in winter (p<0.001). ERalpha was identified in corticotrophs. This study is the first to demonstrate ERalpha expression in corticotrophs and the adrenal cortex in dogs, providing evidence for sexual dimorphism and seasonal variations. PMID- 26850532 TI - Therapeutic effect of anti-feline TNF-alpha monoclonal antibody for feline infectious peritonitis. AB - Feline infectious peritonitis virus (FIPV) replication in macrophages/monocytes induced tumor necrosis factor (TNF)-alpha production, and that the TNF-alpha produced was involved in aggravating the pathology of FIP. We previously reported the preparation of a feline TNF-alpha (fTNF-alpha)-neutralizing mouse monoclonal antibody (anti-fTNF-alpha mAb). This anti-fTNF-alpha mAb 2-4 was confirmed to inhibit the following fTNF-alpha-induced conditions in vitro. In the present study, we investigated whether mAb 2-4 improved the FIP symptoms and survival rate of experimentally FIPV-inoculated SPF cats. Progression to FIP was prevented in 2 out of 3 cats treated with mAb 2-4, whereas all 3 cats developed FIP in the placebo control group. Plasma alpha1-glycoprotein and vascular endothelial growth factor levels were improved by the administration of mAb 2-4, and the peripheral lymphocyte count also recovered. These results strongly suggested that the anti fTNF-alpha antibody is effective for the treatment of FIP. PMID- 26850533 TI - Effects of electromagnetic field (1.8/0.9 GHz) exposure on growth plate in growing rats. AB - The purpose of this study was to determine the effects of whole-body electromagnetic field (EMF) exposure on growth plates in growing male rats. Two groups of rats were exposed to either 900 MHz EMF or 1800 MHz EMF 2 h/day for 90 days. Sham control rats were kept under similar conditions without exposure to the EMF. The rats in the EMF group experienced a more rapid weight gain and increase in length (p < 0.05). Calcium, growth hormone, estradiol and testosterone levels in the EMF groups were higher (p < 0.05). The Safranin O staining density of femoral growth plate was lowest in the reserve zone of rats exposed to 1800 MHz and was increased in the proliferative zone of the control group (p < 0.05). The trabecular zone was thinnest among all zones and the reserve and proliferative zones were thicker (p < 0.05) than other zones in 1800 MHz group.In conclusion, 1800 MHz and 900 MHz EMF may cause prolong the growth phase in growing rats. PMID- 26850534 TI - Alterations in innate immunity reactants and carbohydrate and lipid metabolism precede occurrence of metritis in transition dairy cows. AB - The overall purpose of the present study was to search for early screening biomarkers of disease state. Therefore the objectives of this study were to evaluate metabolites related to carbohydrate metabolism, acute phase proteins, and proinflammatory cytokines in the blood of transition dairy cows starting at 8 weeks before calving. Blood samples were collected from 100 multiparous Holstein dairy cows during -8, -4, disease diagnosis, +4 and +8 weeks relative to parturition. Six healthy cows and 6 cows that showed clinical signs of metritis were selected for serum analysis. Overall the results showed that cows with metritis had greater concentration of lactate, interleukin-6 (IL-6), tumor necrosis factor (TNF), and serum amyloid A (SAA) versus healthy cows throughout the experiment. The disease was associated with decrease in milk production and fat: protein ratio. Cows with metritis showed alteration in metabolites related to carbohydrate metabolism, acute phase proteins, and proinflammatory cytokines starting at -8 weeks prior to parturition and appearance of clinical signs of the disease. This study suggests a possible use of cytokines as early markers of disease in dairy cows. PMID- 26850535 TI - Infection of goats with goatpox virus triggers host antiviral defense through activation of innate immune signaling. AB - Goatpox, caused by goatpox virus (GTPV), is one of the most serious infectious diseases associated with high morbidity and mortality in goats. However, little is known about involvement of host innate immunity during the GTPV infection. For this, goats were experimentally infected with GTPV. The results showed that GTPV infection significantly induced mRNA expression of type I interferon (IFN)-alpha and IFN-beta in peripheral blood lymphocytes, spleen and lung. In addition, GTPV infection enhanced expression of several inflammatory cytokines, including interleukin (IL)-1beta, IL-6, IL-18; and tumor necrosis factor-alpha (TNF-alpha). Strikingly, infection with GTPV activated signal transducers and activators of transcription 3 (STAT3), a critical cytokine signaling molecule. Interestingly, the virus infection induced expression of suppressor of cytokine signaling (SOCS) 1. Importantly, the infection resulted in an increased expression of some critical interferon-stimulated genes, such as interferon-induced transmembrane protein (IFITM) 1, IFITM3, interferon stimulated gene (ISG) 15 and ISG20. Furthermore, we found that infection with GTPV up-regulated expression of Toll like receptor (TLR) 2 and TLR9. These results revealed that GTPV infection activated host innate immune signaling and thereby triggered antiviral innate immunity. The findings provide novel insights into complex mechanisms underlying GTPV-host interaction and pathogenesis of GTPV. PMID- 26850536 TI - Determining the persistence of Mycobacterium bovis bacille Calmette-Guerin Danish in select tissues of orally vaccinated feral swine (Sus scrofa ssp.). AB - Mycobacterium bovis bacille Calmette-Guerin (BCG) is being considered for vaccination of feral swine (Sus scrofa ssp.). Since BCG is a live bacterium, evaluation of its safety and persistence in tissues is important. Fifteen feral swine received approximately 4.5 * 10(6) colony forming units of BCG Danish via oral bait. Four animals received bait without BCG. At 1, 3, 6, and 9 months post vaccination, four vaccinates were euthanized. Non-vaccinates were euthanized at 9 months. Clinical signs were not noted in vaccinated pigs at any time. Tissues from all 20 pigs were culture-negative for mycobacteria. Based on our data, BCG is safe and appears not to persist in feral swine tissues after one month post oral vaccination. However, further work must be performed at higher doses, and on a larger number of animals representing the target population, and further evaluation of persistence in tissues within the first month post-vaccination is needed. PMID- 26850537 TI - Prevalence of Streptococcus equi subsp. equi in horses and associated risk factors in the State of Rio Grande do Sul, Brazil. AB - The aim of this study was to estimate the prevalence of equine strangles and to identify associated risk factors for this disease through a cross-sectional study of nasal swabs. Nasal swabs (n=1010) from healthy equines (absence of nasal discharge, lymphadenopathy and cough) from 341 farms were plated on 5% blood agar; of these horses, 24 were identified as positive for Streptococcus equi through isolation, PCR and DNA sequencing. The estimated prevalence for individual animals was 2.3%, and for herds, it was 5.86%. Statistical analysis identified the following as associated risk factors: the number of group events that were attended by the equines (PR: 1.06); the sharing of food containers (PR: 3.74); and at least one previous positive diagnosis of strangles on the farm (PR: 3.20). These results constitute an epidemiological contribution to the horse industry and may support measures for the future control of the disease. PMID- 26850539 TI - Detection and isolation of digital dermatitis treponemes from skin and tail lesions in pigs. AB - Pig skin lesions are common significant welfare issues, and can cause large economic losses, due to culling of severely affected animals or carcass condemnation at slaughter. It was considered that the treponemal bacteria associated with digital dermatitis (DD) lesions in cattle, sheep and goats may have a role in these pig lesions. Specific diagnostic PCR assays for three cultivable DD Treponema phylogroups were used to survey relevant porcine lesion samples. Using these assays, DD treponemes were detected in 88% (22/25), 72% (8/11) and 82% (14/17) of tail, ear and flank lesions, respectively. Mouth swabs from animals kept in enclosures with high prevalence of skin lesions were positive for the DD treponemes, but not in enclosures with low lesion prevalence. Culture of treponemes from skin lesions resulted in pure isolates of all three DD associated phylogroups. This study shows a strong association of DD treponemes with a range of pig skin lesions. PMID- 26850538 TI - Retardation of fracture healing by cerclage wire near the elbow in radius fracture models. AB - Cerclage wire is widely used in the treatment of fracture internal fixation and is shown effective in clinic. But a report by S.L. has pointed that the wire loop delayed the growth of bone. We have established a radius fracture model to study the possible detrimental effects of cerclage wire on fracture healing and the potential mechanism. By high-resolution CT analysis cerclage wire is found to delay fracture healing, by histological assessment cerclage wire is found to extended the time of hematoma and the marrow cavity appearing, by confocal microscopy cerclage wire decreased the content of calcium and the expression of alkaline phosphatase (ALP), and by RT-PCR analysis cerclage wire decreased the mRNA levels of bone sialoprotein and ALP. These results suggest that the cerclage wire near the elbow delayed the fracture healing in radius fracture models. PMID- 26850540 TI - Endothelial differentiation of canine yolk sac cells transduced with VEGF. AB - Yolk sac (YS) is the site of blood-cell production where primitive erythroid cells originate and complete their maturation. YS is a source of precursor cells, however its differentiation potential and suitability for cell therapies are not well described. YS can be a cell source when neovascularization is required. This study characterized YS canine cells, transduced with VEGF, to analyze then using Immunocytochemistry, flow cytometry and real time PCR. Immunocytochemistry: positive expression for CD105, PCNA, VEGF and vWF, flow cytometry for CD105, VEGF, PCNA, OCT-4 and RT-qPCR for VEGF, CD31, CD105, PCNA and FLT - 1, indicating that these cells have characteristics of endothelial progenitor and pluripotency. After transduction, the YS cells changed their morphology and showed endothelial like cells. We suggest, because of their cell surface phenotype as well as their capacity to differentiate into endothelial-like cells, that canine YS represents a source of cells for neovascularization therapies. PMID- 26850541 TI - Larvicidal potential of carvacrol and terpinen-4-ol from the essential oil of Origanum vulgare (Lamiaceae) against Anopheles stephensi, Anopheles subpictus, Culex quinquefasciatus and Culex tritaeniorhynchus (Diptera: Culicidae). AB - Mosquito-borne diseases represent a deadly threat for millions of people worldwide. However, the use of synthetic insecticides to control Culicidae may lead to resistance, high operational costs and adverse non-target effects. Nowadays, plant-borne mosquitocides may serve as suitable alternative in the fight against mosquito vectors. In this study, the mosquito larvicidal activity of Origanum vulgare (Lamiaceae) leaf essential oil (EO) and its major chemical constituents was evaluated against the malaria vectors Anopheles stephensi and An. subpictus, the filariasis vector Culex quinquefasciatus and the Japanese encephalitis vector Cx. tritaeniorhynchus. The chemical composition of the EO was analyzed by gas chromatography-mass spectroscopy. GC-MS revealed that the essential oil of O. vulgare contained 17 compounds. The major chemical components were carvacrol (38.30%) and terpinen-4-ol (28.70%). EO had a significant toxic effect against early third-stage larvae of An. stephensi, An. subpictus, Cx. quinquefasciatus and Cx. tritaeniorhynchus, with LC50 values of 67.00, 74.14, 80.35 and 84.93 MUg/ml. The two major constituents extracted from the O. vulgare EO were tested individually for acute toxicity against larvae of the four mosquito vectors. Carvacrol and terpinen-4-ol appeared to be most effective against An. stephensi (LC50=21.15 and 43.27 MUg/ml, respectively) followed by An. subpictus (LC50=24.06 and 47.73 MUg/ml), Cx. quinquefasciatus (LC50=26.08 and 52.19 MUg/ml) and Cx. tritaeniorhynchus (LC50=27.95 and 54.87 MUg/ml). Overall, this research adds knowledge to develop newer and safer natural larvicides against malaria, filariasis and Japanese encephalitis mosquito vectors. PMID- 26850542 TI - Permissive growth of human adenovirus type 4 vaccine strain-based vector in porcine cell lines. AB - In recent years, there has been considerable interest in using adenoviruses as live vectors to develop recombinant vaccines. Previous studies have demonstrated the safety and effectiveness of HIV/SIV and influenza vaccine candidates based on human adenovirus type 4 (Ad4) replication-competent vectors in rhesus macaque and human model. To explore the possibility of human Ad4 vaccine strain used as a vector in developing porcine vaccines, the growth properties of replication competent human Ad4 vaccine strain recombinant encoding EGFP in different porcine cell lines were investigated. All tested cell lines are permissive for Ad4 vaccine strain vector with varied replication efficiency. Thus, human Ad4 based vectors would be promising supplement to adenovirus vectors as a delivery vehicle for recombinant vaccines in swine industry. PMID- 26850543 TI - Dynamic modulation of platelet aggregation, albumin and nonesterified fatty acids during physical exercise in Thoroughbred horses. AB - The effect of exercise on platelet aggregation, albumin and nonesterified fatty acids (NEFAs) values and the correlation among these parameters were evaluated in ten clinically healthy and regularly trained Thoroughbred horses. All horses were subjected to two simulated races. Blood samples were collected by jugular venipuncture before and after the first simulated race (T0PRE and T0POST), every 7 days at rest condition for a month (T1R-T2R-T3R), and before and after the second simulated race (T4PRE and T4POST) in order to assess platelet aggregation, albumin and nonesterified fatty acids (NEFAs) levels. One-way analysis of variance showed a significant effect of exercise (P<0.01) on platelet aggregation, albumin and NEFAs values. A negative correlation between platelet aggregation and albumin or NEFAs values, and a positive correlation between albumin and NEFAs values, were found both at T0POST and T4POST (P<0.05). These findings are likely related to dynamic physiological adaptations to exercise that allow re-establishment of the homeostatic equilibrium of the organism. PMID- 26850544 TI - The effect of transport stress on turkey (Meleagris gallopavo) liver acute phase proteins gene expression. AB - The aim of this study was to investigate the effects of transport-related stress on the liver gene expression of four acute phase proteins (APP), namely alpha1 acid glycoprotein (AGP), C-Reactive Protein (CRP), Serum Amyloid A (SAA) and PIT54, in turkeys (Meleagris gallopavo). A group of seven BUT BIG 6 commercial hens was subjected to a two-hour long road transportation and the quantitative gene expression of APP in the liver was compared to that of a non transported control group. The expression of AGP and CRP mRNA was found to be increased in animals slaughtered after road transport. The presence of AGP protein was also confirmed by immunohistochemistry and Western blotting. The results of this study showed that road-transport may induce the mRNA expression of immune related proteins. The finding that AGP and CRP can be upregulated during transport could suggest their use as for the assessment of turkey welfare during transport. PMID- 26850545 TI - Assessment of fallen equine data in France and their usefulness for epidemiological investigations. AB - Quantitative information about equine mortality is relatively scarce, yet it could be of great value for epidemiology purposes. Several European projects based on the exploitation of data from rendering plants have been developed to improve livestock surveillance. Similar data are available for equines in France but have never been studied to date. The objective of this research was to evaluate the potential of the French Ministry of Agriculture's Fallen Stock Data Interchange (FSDI) database to provide quantitative mortality information on the French equine population. The quality of FSDI equine data from 2011 to 2014 was assessed using complementary data registered in the French equine census database, SIRE. Despite a perfectible quality, the FSDI database proved to be a valuable source for studying the basal patterns of mortality over time in the French equine population as illustrated by the spatial representation of the number of deaths. However, improvements in the FSDI database are needed, in particular regarding the registration of animal identification numbers, in order to detail equine mortality for epidemiology purposes. PMID- 26850546 TI - Investigation into homocysteine [corrected], vitamin E and malondialdehyde as indicators of successful artificial insemination in synchronized buffalo cows (Bubalus bubalis). AB - The aim of this study was to describe modifications in plasma homocysteine (Hcy), vitamin E (VitE) and malondialdehyde (MDA) concentrations in the first 56 days after artificial insemination (AI) in buffalo. Thirty-five buffalo cows were divided, ex post, into three groups on the basis of pregnancy diagnosis: pregnant, not pregnant, with embryonic mortality. Pregnancy was diagnosed by ultrasonography and plasma concentrations of pregnancy-associated glycoproteins (PAGs). Our results showed that, in pregnant buffaloes, included those with embryonic mortality, MDA increased progressively while VitE decreased. In non pregnant buffaloes, MDA and Vit E were unchanged. Hcy concentrations also remained unchanged within each group throughout the study period, but were lower in non-pregnant buffaloes than in the pregnant ones and in those with embryonic mortality. In conclusion, present data suggest that successful pregnancy in buffalo cows might be linked to Hcy metabolism and oxidative stress involvement. PMID- 26850548 TI - Differentiation of UK endemic strains of Salmonella enterica serovar Newport from epidemic North American strains by PCR detection of a truncated bapA chromosomal gene. AB - The aim of this study was to develop a PCR test to detect chromosomal differences between epidemic multidrug resistant (epi-MDR) strains of Salmonella enterica serovar Newport (S. Newport) and non-epi-MDR strains of S. Newport that are endemic to the United Kingdom (UK). Sequence analysis of the biofilm-associated protein A gene (bapA) showed that epi-MDR strains of S. Newport from the United States of America (USA) had a deletion of 309 bp, which was not present in non epi-MDR strains of S. Newport from the UK. A PCR test was developed using primers designed to target this difference and was applied to a panel of S. Newport isolates comprising of strains from the UK (n=20, non-epi-MDR), from the USA (n=10, epi-MDR) and from Canada (n=7). A second panel of isolates (n=73) was used to assess the test specificity, and these isolates consisted of non-Newport Salmonella serovars (n=25), and other epidemic serovars (n=48). Epi-MDR S. Newport isolates produced a characteristic 505 bp amplicon, whereas non-epi-MDR S. Newport isolates produced an 814 bp amplicon. The bapA PCR has potential to discriminate between these S. Newport strains irrespective of their carrying resistance genes. PMID- 26850547 TI - Towards the elimination of excessive cobalt supplementation in racing horses: A pharmacological review. AB - Cobalt is an essential trace element for many vital physiological functions. Cobalt is also known to stabilise hypoxia-inducible transcription factors leading to increased expression of erythropoietin which activates production of red blood cells. This implies that cobalt can be used to enhance aerobic performance in racing horses. If this becomes a pervasive practice, the welfare of racing animals would be at risk because cobalt is associated with cardiovascular, haematological, thyroid gland and reproductive toxicity as observed in laboratory animals and humans. It is expected that similar effects may manifest in horses but direct evidence on equine specific effects of cobalt and the corresponding exposure conditions leading to such effects is lacking. Available pharmacokinetic data demonstrates that intravenously administered cobalt has a long elimination half-life (42-156 h) and a large volume of distribution (0.94 L/kg) in a horse implying that repeated administration of cobalt would accumulate in tissues over time attaining equilibrium after ~9-33 days. Based on these pharmacokinetic data and surveys of horses post racing, threshold cobalt concentrations of 2-10 MUg/L in plasma and 75-200 MUg/L in urine have been recommended. However, there is no clearly defined, presumably normal cobalt supplementation regimen for horses and characterisation of potential adverse effects of any established threshold cobalt concentrations has not been done. This review outlines the strengths and limitations of the existing literature on the pharmacological effects of cobalt in horses with some recommendations on what gaps to bridge to enable the determination of optimal threshold cobalt concentrations in racing horses. PMID- 26850549 TI - A WUR SNP is associated with European Porcine Reproductive and Respiratory Virus Syndrome resistance and growth performance in pigs. AB - Porcine reproductive and respiratory syndrome (PRRS) causes decreased reproductive performance and respiratory problems in pigs. The goals of the current study were 1) to examine whether individual variation applies to infection with PRRSV European strains and 2) to investigate the association of a single nucleotide polymorphism (SNP) WUR10000125 (WUR) at the interferon inducible guanylate-binding protein 1 gene (GBP1) with average daily gain (ADG) in PRRSV infected and uninfected pigs. The experimental procedure consisted of two trials in which pigs from negative PRRSV farms were infected with a wild-type (n=80) or vaccinated with an attenuated European PRRS virus strain (n=40) and then monitored after infection or vaccination. Viral load and ADG were determined for each pig. In a third trial, the ADG for PRRSV-free pigs was monitored. All pigs were genotyped for WUR at the GBP1 gene (AA and AG genotype were defined). Results indicated that there was individual variation in the viral load from pigs challenged with a wild-type or low virulent European PRRSV strain. Secondly, our data showed that WUR SNP was associated to ADG in vaccinated pigs. Thus, ADG in AG pigs was significantly higher than in AA ones after vaccinating with an attenuated PRRSV strain. However, the reverse happened in a PRRSV-free environment where the AA pigs were those that grew faster. Based on these results, there is a scope for selecting pigs according to their responses to PRRS virus infection with European strains and that WUR SNP may play a role in causing PRRSV resistance. PMID- 26850550 TI - Plasmodium spp. In a captive raptor collection of a Safaripark in northwest Italy. AB - Blood parasites infect all vertebrates (Clayton and Moore 1997). Avian malaria parasites (Plasmodium spp., Plasmodiidae) are cosmopolitan in their distribution and are responsible for severe diseases in domestic and wild birds.In September 2009, nine raptorial birds that either arrived recently or were maintained as permanent residents at the Safaripark Pombia (northwest Italy) showed loss of stamina, developing listlessness, anorexia and regurgitation. Within one month three animals died and were necropsied.Following the diagnosis of Plasmodium infection all other raptorial birds were treated: clinical improvement was observed in all birds, and blood smears made after one month resulted negative for parasites. PMID- 26850551 TI - Sequence and partial functional analysis of canine Bcl-2 family proteins. AB - Dogs present with spontaneous neoplasms biologically similar to human cancers. Apoptotic pathways are deregulated during cancer genesis and progression and are important for therapy. We have assessed the degree of conservation of a set of canine Bcl-2 family members with the human and murine orthologs. To this end, seven complete canine open reading frames were cloned in this family, four of which are novel for the dog, their sequences were analyzed, and their functional interactions were studied in yeasts. We found a high degree of overall and domain sequence homology between canine and human proteins. It was slightly higher than between murine and human proteins. Functional interactions between canine pro apoptotic Bax and Bak and anti-apoptotic Bcl-xL, Bcl-w, and Mcl-1 were recapitulated in yeasts. Our data provide support for the notion that systems based on canine-derived proteins might faithfully reproduce Bcl-2 family member interactions known from other species and establish the yeast as a useful tool for functional studies with canine proteins. PMID- 26850552 TI - Temporal and spatial expression of Muc2 and Muc5ac mucins during rat respiratory and digestive tracts development. AB - Secreted mucins constitute a crucial part of the gel that protects respiratory and digestive epithelia, being MUC2/Muc2 the predominant gel-forming mucin of the intestine while MUC5AC/Muc5ac is one of the gel-forming mucins most expressed at the airways. In this study, we have analyzed Muc2 and Muc5ac during rat development by using immunohistochemistry, Western blotting and RT-PCR. We demonstrated that rat Muc2 was expressed in fetal intestinal goblet cells of surface epithelium of villi and developing Lieberkuhn crypts. In neonates and adults, Muc2 was expressed at luminal goblet cells of small and large intestine and at gastric mucous and glandular cells. Muc5ac protein was observed in embryonic gastric and lung samples; expression increased during development and postnatal and adult life. After birth, a low reaction was detected at the tracheal surface epithelium and glands, which increased in adults. PMID- 26850553 TI - Experimental infection with bovine ephemeral fever virus and analysis of its antibody response cattle. AB - Bovine ephemeral fever (BEF) is an arthropod-borne viral disease that occurs throughout mainland China. LS11 obtained in the 2011 BEF epidemic was a wild strain, and its virulence and antibody response have never been studied in China. Therefore, the issues were investigated in this work. Experimental cattle were intravenously infected with different doses of BEF virus, and some non-infected cattle were simultaneously monitored. Blood and serum samples were collected from all animals over the course of our study. Infected cattle were challenged for a second time with BEF virus to determine protective period of the antibodies. BEF virus was detected in blood samples from infected cattle, but not in monitored cattle. The neutralizing antibodies (nAbs) against BEFV were easier to be detected and persisted for longer periods in cattle infected with higher doses of BEFV than in those infected with lower doses. When the titer of nAbs was equal to 5 or 6, re-infected cattle still could mount a challenge against BEFV. However, after 3 or 6months, when nAbs were no longer apparent, re-infected cattle displayed typical symptoms of BEF. Our findings indicated that vaccination should be performed once the titer of nAb decreased to 5 or 6. PMID- 26850555 TI - Response of antimicrobial peptides from porcine neutrophils to pentoxifylline and antigens from Gram negative and Gram positive bacteria. AB - Neutrophils, the main component of the defense against invading organisms have also been implicated in tissue damage in numerous inflammatory conditions. Neutrophil products can degrade the extracellular matrix and when excessively released are thought to cause some disorders. As it is known, pentoxifylline (PTX) can suppress a range of neutrophil responses. Cathelicidins are components of the early host defenses against infection, however, in most cases cleavage with elastase is necessary to obtain active forms. Thus, the aim of our study was to assess the usage of PTX as a factor which could inhibit some neutrophil functions, and to assess if PTX can lead to the impairment of the release from these cells active cathelicidins. For these purposes we determined neutrophil activity as well as expression of cathelicidins from porcine neutrophils in cultures under the influence of PTX. PTX exerted an inhibitory effect on elastase and MPO release from neutrophils. At lower concentrations of PTX, ALP release was inhibited both in cultures stimulated with PTX+fMLP and with PTX+LPS. Inhibition of superoxide generation was insignificant, whereas a decrease of NO production was noted. The MALDI TOF analysis revealed that in all cultures stimulated with PTX+fLMP and PTX+LPS there was no inhibition of the release of cathelicidins in comparison with cultures stimulated only with fMLP and only with LPS. Our study proved that although PTX in porcine neutrophils is able to suppress many neutrophil functions, the expression of cathelicidins is maintained. PMID- 26850554 TI - Oral vaccination with a rough attenuated mutant of S. Infantis increases post wean weight gain and prevents clinical signs of salmonellosis in S. Typhimurium challenged pigs. AB - We show that oral inoculation of 14 day old conventional piglets with a rough attenuated Salmonella enterica serovar Infantis 1326/28F(r) (serogroup C1), 24h prior to oral challenge with S. enterica serovar Typhimurium 4/74 (serogroup B), resulted in significant weight gain (~10%) measured at 14 days post-weaning (38 days of age). Two days after challenge the S. Typhimurium induced stunting and, in some cases loss, of villi but this was prevented by pre-inoculation with the S. Infantis strain. The clinical signs of disease associated with S. Typhimurium 4/74 challenge and faecal shedding were also significantly (P<0.05) reduced by pre-inoculation with the S. Infantis mutant. Pre-inoculation of pigs with the S. Infantis mutant also increased weight gain in pigs challenged with pathogenic Escherichia coli. However, Mycobacterium bovis BCG, an unrelated intracellular bacterium, did not protect against challenge with S. Typhimurium 4/74. PMID- 26850556 TI - Calcium homeostasis in mitochondrion-mediated apoptosis of chick embryo cecal epithelial cells induced by Eimeria tenella infection. AB - In this study, the process of Eimeria tenella-induced apoptosis and the effect of calcium homeostasis were investigated in chick embryo cecal epithelial cells. In particular, we examined cytochrome c release into the cytoplasm, mitochondrial permeability transition pore (MPTP) opening, and changes in [Ca(2+)]c and apoptosis in host cells. Apoptosis, MPTP opening, cytochrome c release, and [Ca(2+)]c in host cells increased following infection. This trend was reversed by blocking the increase in [Ca(2+)]c using BAPTA/AM and EGTA (intra- and extracellular chelators of Ca(2+), respectively) and by applying heparin sodium and ryanodine (blockers of the inositol triphosphate and ryanodine receptors of the endoplasmic reticulum, respectively). These results indicate that [Ca(2+)]c plays a significant role in host cell mitochondrial apoptosis, which is induced via modulation of extracellular Ca(2+) levels and endoplasmic reticulum Ca(2+) channels. Thus, agents that restore Ca(2+) homeostasis may be useful for managing E. tenella infection in chickens. PMID- 26850558 TI - Immunogenicity of a recombinant Sendai virus expressing the capsid precursor polypeptide of foot-and-mouth disease virus. AB - In this study, SeV was used as a vector to express capsid precursor polypeptide (P1) of Foot-and-mouth disease virus (FMDV) by using reverse genetics. The rescue recombinant SeV (rSeV-P1) can efficiently propagate and express P1 protein by Western blot and IFA analysis. To evaluate the immunogenicity of rSeV-P1, BALB/c mice were divided into several groups and immunized intramuscularly with various doses of rSeV-P1, rSeV-eGFP, PBS and commercial FMD vaccine, respectively, and then challenged with an intraperitoneal injection of 1 * 10(6) TCID50 of virulent serotype O FMDV O/ES/2001 strain 4 weeks after booster immunization. Mice vaccinated with rSeV-P1 acquired FMDV-specific ELISA antibodies, neutralizing antibodies as well as cellular immune response. Meantime, mice immunized with rSeV-P1 (dose-dependent) had the ability to inhibit the replication of FMDV in the sera after FMDV challenge. Our results indicated that the recombinant SeV-P1 virus could be utilized as an alternative strategy to develop a new generation of safety and efficacious vaccine against FMDV infection. PMID- 26850557 TI - Design and evaluation of a polytope construct with multiple B and T epitopes against Tembusu virus infection in ducks. AB - Tembusu virus (TMUV) is a newly emerging pathogenic flavivirus that is causing massive economic loss in Chinese poultry industry; until now, there is no effective vaccine or drug for its prevention. Epitope-based vaccination is a promising approach to achieve protective immunity and to avoid immunopathology. In present study, based on in silico epitope selection, we optimized and proposed a polytope DNA vaccine (pVAX1-rTEM) consisting B-cell and T cell epitopes from the TMUV envelope (E) protein. The immunogenicity and protective efficacy of constructed polytope DNA vaccine was assessed by in vitro and in vivo experiments. In in vitro assays, the expressed pVAX1-rTEM showed reactivity with Tembusu positive serum. Its protective efficacy against TMUV infection was evaluated in ducks. The results showed that pVAX1-rTEM was highly immunogenic and could elicit high titer neutralizing antibodies and cell-mediated immune responses. These results indicate that pVAX1-rTEM may be a promising candidate vaccine for prevention of TMUV infection. PMID- 26850559 TI - Porcine circovirus type 2 induces type I interferon production via MyD88-IKKalpha IRFs signaling rather than NF-kappaB in porcine alveolar macrophages in vitro. AB - Type I interferon (IFN-I) plays important roles in host antiviral responses. The interferon regulatory factor (IRF) and NF-kappaB transcription factors are thought to be important in the processes of viral secretion and triggering of interferon production. Recently, studies have shown that porcine circovirus type 2 (PCV2) can induce IFN-I production in vivo and in vitro, but the mechanisms underlying the production of PAMs infected with PCV2 remains unknown. Treatment of these cells with BAY11-7082, an inhibitor of NF-kappaB activation, allowed us to study the secretion of IFN-alpha and IFN-beta in PAMs infected with PCV2. We found that IFN-alpha expression was induced following virus infection of PAMs. Notably, even after inhibitor treatment of PAMs infected with PCV2, secretion of IFN-alpha was significantly higher (P<0.05) compared with the PCV2 infection alone group. Our findings suggest that NF-kappaB plays a minor role in PCV2 induced type I interferon responses. To further characterize the signaling pathway that drives IFN-I expression in PAMs in response to PCV2, we used siRNA to silence the expression of Myeloid differentiation factor 88 (MyD88) and study the role of MyD88-IKKalpha-IRF signaling in IFN-I production in PAMs induced by PCV2. Our findings show that PCV2 induced IFN-alpha mRNA transcription, which is associated with the activities of MyD88, IRF7, and IRF3. Thus, PCV2 can induce IFN-I transcription via the MyD88-IKKalpha-IRF signaling axis. PMID- 26850561 TI - Impact of the amount of straw provided to pigs kept in intensive production conditions on the occurrence and severity of gastric ulceration at slaughter. AB - This study examined effects of the amount of straw offered on occurrence and severity of gastric lesions in pigs kept in pens (18 pigs, 0.7 m(2)/pig) with partly slatted flooring and 10, 500 or 1000 g straw/pig/day from 30 kg live weight. The pigs had ad libitum access to dry feed. Forty-five pigs were used, three from each of 15 pens. After euthanization, the dimension of the non glandular region of the stomach was measured. Lesions were characterized and scored. Irrespective of straw provided, 67% of the pigs showed signs of gastric pathology. Pigs provided with 500 or 1000 g straw were pooled as 'permanent access'. The proportion of pigs with ulcerations was reduced by permanent access to straw (7 vs. 33%; P<0.05), suggesting that permanent access to straw may improve animal health, and be considered as one possible strategy to limit gastric ulceration in pigs. PMID- 26850560 TI - Pain-related behavior was not observed in dairy cattle in the days after liver biopsy, regardless of whether NSAIDs were administered. AB - For liver biopsy in cattle, it is routine practice to only provide local anesthesia (LA) to the skin and muscle layers, with visceral tissues remaining unanesthetized. Cattle being biopsied may therefore benefit from additional analgesia. This study aimed to determine if non-steroidal anti-inflammatory drugs would decrease post-biopsy pain in cattle. Twenty-four dairy cows were allocated into four treatment groups: biopsy under LA only; biopsy under LA with ketoprofen; biopsy under LA with meloxicam; and a sham-biopsied control group. Behavior was observed for 4h immediately following biopsy, and for 2h each day for the first three days after biopsy. No significant differences in behavior were found between any treatment groups on any day. This suggests that any post biopsy pain present was not of enough significance to alter the cows' normal behavior patterns. Without identifying post-biopsy pain, it is not possible to determine what effect NSAID analgesia may have had on alleviating it. PMID- 26850562 TI - Headaches and intraventricular hyperattenuating areas on brain CT. PMID- 26850563 TI - Intrinsic features of the CD8alpha(-) dendritic cell subset in inducing functional T follicular helper cells. AB - T follicular helper (Tfh) cells, a true B cell helper, have a critical role in enhancing humoral immune responses. However, the initial differentiation of Tfh cells by dendritic cells (DCs), the most potent antigen presenting cells, has not been clearly understood, particularly in the knowledge of the two major conventional dendritic cell subsets, CD8alpha(+) DCs or CD8alpha(-) DCs. Here we demonstrated that the localization of CD8alpha(-) DCs in the marginal zone (MZ) bridging channels is closely associated with the induction of CXCR5(+)CCR7(low) Tfh cells. We also showed that the major source of IL-6 for inducing Tfh cells is provided from the activated CD4(+) T cells induced by CD8alpha(-) DCs, and IL-6 directly secreted from the DC subsets seems minor. CD8alpha(-) DCs were superior in inducing functional Tfh cells over other antigen presenting cells including B cells. We here observed the unknown intrinsic features of the DC subsets, suggesting the potential of utilizing the CD8alpha(-) DC subset as therapeutic vaccine for the regulation of humoral immune responses. PMID- 26850564 TI - Plant microbiota affects seed transmission of phytopathogenic microorganisms. PMID- 26850565 TI - Contrast-enhancement ratio on multiphase enhanced computed tomography predicts recurrence of pancreatic neuroendocrine tumor after curative resection. AB - BACKGROUND/OBJECTIVE: No previous study has quantitatively investigated the degree of enhancement of pancreatic neuroendocrine tumors (pNETs) using a routine preoperative modality. The aim of this study was to evaluate the contrast enhancement ratio (CER) of pNETs using multiphase enhanced CT and to assess the impact of the CER on disease recurrence after surgery. METHODS: A retrospective study was performed using data from 47 consecutive patients with pNETs who had undergone curative surgery. The CER of the tumor was calculated by dividing the CT attenuation value obtained during the maximum-enhanced phase by that obtained during the pre-enhanced phase. A region of interest was placed in the largest tumor dimension plane so as to cover as much surface of the tumor as possible while avoiding adjacent normal structures, calcification, and necrotic areas of the tumor. RESULTS: During a median follow-up period of 51 months (range, 1-132 months), a total of 4 patients (8.5%) developed disease recurrence. The median CER value was significantly lower for the patients with recurrence than for the patients without recurrence (2.9 vs. 4.3, P = 0.013). Univariate analyses showed that a CER <=3.2 was significantly associated with disease recurrence (P < 0.001). All the patients with disease recurrence had tumors that were both large (>20 mm) and weakly enhanced (CER <= 3.2), whereas no recurrences were observed even in patients with tumors >20 mm when the CER was greater than 3.2. CONCLUSIONS: CER might be a useful predictor of disease recurrence in patients with pNETs. PMID- 26850567 TI - Gold(I)-Catalyzed Allenyl Cope Rearrangement: Evolution from Asynchronicity to Trappable Intermediates Assisted by Stereoelectronic Switching. AB - Pericyclic reactions bypass high-energy reactive intermediates by synchronizing bond formation and bond cleavage. The present work offers two strategies for uncoupling these two processes and converting concerted processes into their "interrupted" versions by combining Au(I) catalysis with electronic and stereoelectronic factors. First, we show how the alignment of the C3-C4 bond with the adjacent pi systems can control the reactivity and how the concerted scission of the central sigma bond is prevented in the boat conformation. Second, the introduction of a fluorine atom at C3 also interrupts the sigmatropic shift and changes the rate-determining step of the interrupted cascade from the 6-endo-dig nucleophilic attack to the fragmentation of the central C3-C4 bond. Furthermore, this effect strongly depends on the relative orientation of the C-F bond toward the developing cationic center. The equatorial C-F bond has a much greater destabilizing effect on TS2 due to the more efficient through-bond interaction between the acceptor and the cationic pi system. In contrast, the axial C-F bond is not aligned with the bridging C-C bonds and does not impose an equally strong deactivating stereoelectronic effect. These differences illustrate that the competition between concerted and interrupted pericyclic pathways can be finely tuned via a combination of structural and electronic effects modulated by conformational equilibria. The combination of Au(I) catalysis and C-F-mediated stereoelectronic gating delays the central bond scission, opening access to the interrupted Cope rearrangements and expanding the scope of this classic reaction to the design of new cascade transformations. PMID- 26850566 TI - Validation and Establishment of an Interval-Level Measure of the Balance Assessment in Sitting and Standing Positions in Patients With Stroke. AB - OBJECTIVE: To validate the psychometric properties of the Balance Assessment in Sitting and Standing Positions, including validity (unidimensionality and concurrent validity), reliability (Rasch reliability), and responsiveness (compared with the Postural Assessment Scale for Stroke Patients [PASS]) and to transform the Balance Assessment in Sitting and Standing Positions from an ordinal-level measure into an interval-level measure. DESIGN: Retrospective cross sectional study. SETTING: Medical records from a medical center. PARTICIPANTS: Patients with stroke (N=1193). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The 4-item Balance Assessment in Sitting and Standing Positions was used, assessing static sitting balance, dynamic sitting balance, static standing balance, and dynamic standing balance. RESULTS: Data of 1193 patients with stroke were included for Rasch analysis. The 4 items of the Balance Assessment in Sitting and Standing Positions constituted a unidimensional construct (infit/outfit mean square, .75-1.05), had good concurrent validity (r=.70-.90), and had sufficient Rasch reliability (.93). The Balance Assessment in Sitting and Standing Positions had large responsiveness (effect size, 1.20; standardized response mean, 1.51) and was comparable with the PASS (effect size, .90; standardized response mean, 1.32). CONCLUSIONS: The Balance Assessment in Sitting and Standing Positions has sound psychometric properties. The transformed-Rasch scores of the Balance Assessment in Sitting and Standing Positions can be used to identify patients' balance function and detect patients' changes. PMID- 26850568 TI - An analysis of the teaching of intravenous self-administration in patients with hereditary angio-oedema. AB - BACKGROUND: Hereditary angio-oedema (HAE), C1 inhibitor HAE (C1-INH-HAE) type I and C1-INH-HAE type II, are inherited disorders characterised by potentially life threatening recurrent swellings, caused by a deficiency of C1 inhibitor. Management includes attack treatment or prevention using prophylaxis/routine prevention. AIM: To evaluate the success of self-administration training as part of a home care programme for treatment of HAE using intravenous C1 inhibitor. METHODS: In total, 18 patients (7 men, 11 women; aged 18-72 years) were trained to self-administer a plasma-derived C1 inhibitor concentrate for acute treatment or routine prevention of HAE attacks. The number of training sessions needed to learn intravenous self-administration, delay in time to treatment and reduction in attack frequency (per month) were evaluated after completion of the training. RESULTS: All patients successfully completed training. The median number of training sessions required to be capable of unassisted/independent self-injection was 5 (range 2-30). Time to treatment was reduced from a median of 4.5 h (270 min) by medical professionals to 15 min by patients after self-administration training). Using the treatment as routine prevention resulted in a reduction of median frequency of attacks from 8 to 0.5 attacks/month. CONCLUSION: C1 inhibitor self-administration for the treatment of HAE allows patients to quickly treat attacks at home, potentially reducing attack severity. The results also demonstrate the benefit of self-administered routine prevention therapy in a real world patient population. Self-administered therapy potentially allows patients to gain greater control over their attacks, resulting in a reduction in healthcare utilization. PMID- 26850570 TI - Morphometric human embryonic brain features according to developmental stage. AB - OBJECTIVES: The present study investigated linear, area, and volume measurements of human brain samples according to Carnegie stages (CS) in an attempt to select suitable morphometric features that reflect embryonic development. METHODS: Using magnetic resonance imaging, we measured seven linear segments, three separate areas, and three regional volumes in 101 samples between CS13 and 23. Brain volume was determined via manual segmentation of the magnetic resonance image, whereby a formula was generated to estimate the volume of each linear measurement. RESULTS: All parameters correlated with crown-rump length. Bitemporal length and mesencephalic height increased linearly according to the CS, and a high correlation between bitemporal length and both whole-brain (r = 0.98) and prosencephalon (r = 0.99) volumes was found when brain cavity volume was excluded. CONCLUSION: Morphometric data related to human embryonic stages are valuable for correcting and comparing sonographic data. The present approach may contribute to improvements in prenatal diagnostics by enabling the selection of more suitable measurements during early embryonic stages. (c) 2016 John Wiley & Sons, Ltd. PMID- 26850569 TI - Implementation of a pharmacogenomics consult service to support the INGENIOUS trial. AB - Hospital systems increasingly utilize pharmacogenomic testing to inform clinical prescribing. Successful implementation efforts have been modeled at many academic centers. In contrast, this report provides insights into the formation of a pharmacogenomics consultation service at a safety-net hospital, which predominantly serves low-income, uninsured, and vulnerable populations. The report describes the INdiana GENomics Implementation: an Opportunity for the UnderServed (INGENIOUS) trial and addresses concerns of adjudication, credentialing, and funding. PMID- 26850571 TI - Duplication 2p25 in a child with clinical features of CHARGE syndrome. AB - CHARGE syndrome is a dominant disorder characterized by ocular colobomata, heart defects, choanal atresia, retardation of growth and development, genital hypoplasia, and ear abnormalities including deafness and vestibular disorders. The majority of individuals with CHARGE have pathogenic variants in the gene encoding CHD7, a chromatin remodeling protein. Here, we present a 15-year-old girl with clinical features of CHARGE syndrome and a de novo 6.5 Mb gain of genomic material at 2p25.3-p25.2. The duplicated region contained 24 genes, including the early and broadly expressed transcription factor gene SOX11. Analysis of 28 other patients with CHARGE showed no SOX11 copy number changes or pathogenic sequence variants. To our knowledge, this child's chromosomal abnormality is unique and represents the first co-occurrence of duplication 2p25 and clinical features of CHARGE syndrome. We compare our patient's phenotype to ten previously published patients with isolated terminal duplication 2p, and elaborate on the clinical diagnosis of CHARGE in the context of atypical genetic findings. PMID- 26850572 TI - Chronic 5-HT4 receptor agonist treatment restores learning and memory deficits in a neuroendocrine mouse model of anxiety/depression. AB - Cognitive disturbances are often reported as serious invalidating symptoms in patients suffering from major depression disorders (MDD) and are not fully corrected by classical monoaminergic antidepressant drugs. If the role of 5-HT4 receptor agonists as cognitive enhancers is well established in naive animals or in animal models of cognitive impairment, their cognitive effects in the context of stress need to be examined. Using a mouse model of anxiety/depression (CORT model), we reported that a chronic 5-HT4 agonist treatment (RS67333, 1.5mg/kg/day) restored chronic corticosterone-induced cognitive deficits, including episodic-like, associative and spatial learning and memory impairments. On the contrary, a chronic monoaminergic antidepressant drug treatment with fluoxetine (18mg/kg/day) only partially restored spatial learning and memory deficits and had no effect in the associative/contextual task. These results suggest differential mechanisms underlying cognitive effects of these drugs. Finally, the present study highlights 5-HT4 receptor stimulation as a promising therapeutic mechanism to alleviate cognitive symptoms related to MDD. PMID- 26850573 TI - Effect of intermittent hypoxic training on hypoxia tolerance based on single channel EEG. AB - A single-channel algorithm was proposed in order to study effect of intermittent hypoxic training on hypoxia tolerance based on EEG pattern. EEG was decomposed by ensemble empirical mode decomposition into a finite number of intrinsic mode functions (IMFs) based on the intrinsic local characteristic time scale. Analytic amplitude, analytic frequency, and recurrence property quantified by recurrence quantification analysis were explored on IMFs, and the first two scales revealed difference between normal EEG and hypoxia EEG. Classification accuracy of hypoxia EEG and normal EEG could reach 67.8% before decline of neurobehavioral ability, which represented that hypoxia EEG pattern could be detected at an early stage. Classification accuracy of hypoxia EEG and normal EEG increased with time and deepened intensity of hypoxia was observed by regular shift of hypoxia EEG pattern with time in a three dimensional subspace. The reduced shift and classification accuracy after intermittent hypoxic training represented that hypoxia tolerance enhanced. PMID- 26850574 TI - Correlation of hemodynamic and fluorescence signals under resting state conditions in mice's barrel field cortex. AB - Both neurons and astrocytes are known to affect local vascular response in the brain following neuronal activity. In order to differentiate the contributions of each cell type to the hemodynamic response during stimulation and resting state, intrinsic optical signal (IOI) was recorded synchronized with fluorescence imaging of calcium concentration sensitive dye Oregon Green BAPTA-1 AM. By changing the stimulation parameters (frequency and duration), it was possible to individually promote neuronal and glial responses and to compare them to levels of oxy (HbO), deoxy (HbR) and total (HbT) hemoglobin concentrations. Finally, resting state recordings were done to investigate the possible correlation between hemoglobin fluctuation and calcium transients, based on different frequency bands associated either with neuronal or glial activity. PMID- 26850576 TI - Dendritic branching angles of pyramidal cells across layers of the juvenile rat somatosensory cortex. AB - The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II-VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567-2576, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26850575 TI - Understanding the FOLFOXIRI-regimen to optimize treatment for metastatic colorectal cancer. AB - The management of metastatic colorectal cancer substantially improved over the last 10 years and median overall survival of patients might exceed 30 months. The selection of an effective first-line treatment represents a crucial point in order to achieve good outcome results. In the last years, the intensive FOLFOXIRI regimen in combination with bevacizumab became a new standard option in this setting. In the present review we summarized the main steps of FOLFOXIRI regimen development from the first pilot study to the recent findings with biological agents, with a specific focus on practical aspects, such as patient's selection, adverse event management, treatment schedules and post-progression strategies. Possible predictive markers, open issues and ongoing clinical trials have been also deeply described. PMID- 26850577 TI - Does Reducing Inpatient Length of Stay Have Upstream Effects on the Emergency Room: Exploring the Impact of the General Internal Medicine Care Transformation Initiative. AB - OBJECTIVE: The General Internal Medicine (GIM) Care Transformation Initiative implemented at one of four teaching hospitals in the same city resulted in improved efficiency of in-hospital care. Whether it had beneficial effects upstream in the emergency department (ED) is unclear. METHODS: Controlled before after study of ED length of stay (LOS) and crowding metrics for the intervention site (n = 108,951 visits) compared to the three other teaching hospitals (controls, n = 300,930 visits). Our primary outcome was ED LOS for GIM patients but secondary outcomes included ED LOS for all adults and ED crowding metrics. RESULTS: The GIM Care Transformation was associated with an additional 2.8-hour reduction in median ED LOS (from 25.6 hours to 13.5 hours) over and above the 9.3 hour decline (from 30.6 hours to 21.3 hours) seen in the three control EDs for GIM patients who were hospitalized (p < 0.001). As less than one in 30 ED visits resulted in a GIM ward admission, the median ED LOS for all patients declined by 15 minutes (from 4.6 hours to 4.3 hours, p < 0.001) in the control hospitals and by 30 minutes (from 5.7 hours to 5.1 hours, p < 0.001) at the intervention hospital pre versus post (p = 0.04 for the 15-minute additional reduction, p < 0.001 for level change on interrupted time series). Other metrics of ED crowding improved by similar amounts at the intervention and control hospitals with no statistically significant differences. CONCLUSION: Although the GIM Care Transformation Initiative was associated with substantial reductions in ED LOS for patients admitted to GIM wards at the intervention hospital, it resulted in only minor changes in overall ED LOS and no appreciable changes in ED crowding metrics. PMID- 26850578 TI - Structure of iron saturated C-lobe of bovine lactoferrin at pH 6.8 indicates a weakening of iron coordination. AB - The bilobal lactoferrin is an approximately 76 kDa glycoprotein. It sequesters two Fe(3+) ions together with two CO(3)(2-) ions. The C-terminal half (residues, Tyr342-Arg689, C-lobe) of bovine lactoferrin (BLF) (residues Ala1-Arg689) was prepared by limited proteolysis using trypsin. Both C-lobe and intact BLF were saturated to 100%. Both of them retained up to nearly 85% of iron at pH 6.5. At pH 5.0, C-lobe retained 75% of iron whereas intact protein could retain only slightly more than 60%. At pH 4.0 both contained 25% iron and at pH 2.0 they were left with iron concentration of only 10%. The structure of iron saturated C-lobe was determined at 2.79 A resolution and refined to R(cryst) and R(free) factors of 0.205 and 0.273, respectively. The structure contains two crystallographically independent molecules, A and B. They were found to have identical structures with an r.m.s. shift of 0.5 A for their C(alpha) atoms. A high solvent content of 66% was observed in the crystals. The average value of an overall B-factor was 68.0 A(2). The distance of 2.9 A observed for the coordination bond between Fe(3+) ion and N(e2) of His595 appeared to be considerably longer than the normally observed values of 1.9-2.2 A. This indicated that the coordination bond involving His595 may be absent. Other coordination distances were observed in the range of 2.1-2.3 A. Based on the present structure of iron saturated C-lobe, it may be stated that His595 is the first residue to dissociate from ferric ion when the pH is lowered. PMID- 26850579 TI - [Active response to high momentum of diabetic retinopathy with the strategy of combined treatment and prevention]. AB - Diabetic retinopathy (DR) is an irreversible blinding eye disease. With the increased number of diabetes patients and aging population, China is now facing both the high prevalence rate and blindness rate of DR. It requires us to change the traditional mode and build a comprehensive, community-based system for DR prevention and treatment. The mainline is "Health Education-Screening-Referral Treatment-Follow-up-Health Management". The public health resource and clinical resource should be effectively integrated into this system, so as to control high momentum of DR. PMID- 26850580 TI - [Clarifying some concepts and clinical significance of refractory or recurrent neovascular age-related macular degeneration]. AB - Anti-VEGF therapy is currently one of the main treatments for neovascular age related macular degeneration (nAMD). Clinically, patients under standardized anti VEGF therapy showed different responses, of which recurrences or even insensitivity were found in some patients. However, the specific definitions of these various clinical responses are still unclarified. Therefore, to consolidate and define these concepts are of great importance regarding to future efficacy comparison, treatment response clarification and novel drug switching therapies. PMID- 26850581 TI - [The efficiency of 810 nm diode laser photocoagulation for type1 retinopathy of prematurity]. AB - OBJECTIVE: To evaluate diode laser photocoagulation effects in type 1 prethreshold retinopathy of prematurity (ROP) in Peking University People's Hospital. METHODS: Retrospective cross-sectional study. Clinical records of the premature infants treated for type 1 prethreshold ROP from the year of 2008 to 2012 were reviewed. RESULTS: We reviewed 226 infants including 146 male and 80 female. The mean birth weight and the gestational age were 1 386 grams and 30.2 weeks respectively. In all the 384 photocoagulation treated eyes, ROP regressed completely in 381 eyes (99.1%). One eye of zone I ROP progressed to stage 4A. Macula kept attaching after vitrectomy. There was no significant difference of regression rate between Zone I and Zone II of type 1 prethreshold ROP. No severe complications occurred. CONCLUSIONS: Diode laser photocoagulation in type 1 ROP was safe and efficient. PMID- 26850582 TI - [Clinical observation of a new anti-VEGF drugs conbercept for wet age-related macular degeneration]. AB - OBJECTIVE: To observe the efficacy and safety of intravitreal injection of conbercept, a new drugs of VEGFR fusion proteins, on wet age-related macular degeneration (wAMD). METHODS: To analyze retrospectively the clinical data of 58 patients with wet wAMD, which was diagnosed by examination of ETDRS charts, color fundus photograph, fluorescein angiography (FFA) and optical coherence tomography (OCT), were underwent intravitreal injection conbercept 0.5 mg (0.05 ml of 10 g/L). Follow-up time was 6 to 12 months.Visual acuity (ETDRS charts letter), retinal thickness, leakage of CNV and operative complications before and after the treatment were analyzed. RESULTS: Conbercept injection therapeutic times were 3-5, the average therapeutic times were 3.05. At the end of the follow-up period, the mean letter of ETDRS charts was 50.20+/-12.87, increased 26.20 letters (t=2.936, P<0.01). the ETDRS charts improved 15 or more letters in 33 eyes (53.23%), decreased more than 15 letters in 2 eyes (3.23%); the average foveal thickness on OCT images were (223+/-74) um after treatment, decreased significantly (t=3.669, P<0.01) ; FFA showed CNV complete closure in 34 eyes (54.84%), partial closure in 23 eyes (37.10%), no change in 5 eyes (8.06%). IOP increased in 2 eyes after treatment and recovered within one week. CONCLUSIONS: Intravitreal injection of conbercept for wAMD was well tolerated, with an improvement in BCVA, macular edema and leakage of CNV, reduce the risk of rehaemorrhagia. PMID- 26850583 TI - [The clinical study on intravitreous injection of ranibizumab for aggressive posterior retinopathy of prematurity]. AB - OBJECTIVE: To observe the retinal vascular development and changes on aggressive posterior retinopathy of prematurity (AP-ROP) by intravitreal ranibizumab, evaluate the therapeutic effect, and provide the basis for clinical treatment. METHODS: The total of 38 eyes of 19 premature infants who were diagnosed as AP ROP from January 2012 to October 2013 in our hospital were performed intravitreal injection of ranibizumab (0.04 ml). It was observed about the regression of plus diseases, ridges, neovascularization on the ridge and the development of peripheral retinal vessel. Laser photocoagulation were performed for 14 eyes of 7 cases whose plus diseases, ridges and neovascularization on the ridge didn't regress completely after intralvitreal injection of ranibizumab. RESULTS: All infants were found retinopathy regressed and retinal vessels continued to develop peripherally to some degree. Of all infants, 24 eyes of 12 infants were found complete regression of retinopathy, resolution of neovascularization and bleeding and that retinal vessels continued to develop to ora serrata or scarification of peripheral retinopathy. Fourteen eyes of 7 infants were found retinopathy didn't regressed completely and regressed completely after combing intravitreal ranibizumab injection. All 19 infants didn't occure infection, ocular or systemic complications. CONCLUSIONS: The efficacy of intravitreal injection of ranibizumab is good for AP-ROP. It can made ridge, neovascularization on the ridge and plus disease regress, as well as let the retinal vessel continue development. Infants with no regressed retinopathy may need combined laser photocoagulation. PMID- 26850584 TI - [Evaluation on the noninvasive measurement of macular pigment optical density by a novel technique]. AB - OBJECTIVE: To evaluate the measurement of macular pigment optical density (MPOD) by a novel instrument MPS1000 as compared to that measured by the traditional heterochromatic flicker photometer (HFP). METHODS: Method-comparative study. MPOD at 0.5 degrees eccentricity was measured simultaneously by the two different instruments in 111 eyes of the 59 healthy subjects. Test-retest variability was evaluated for each instrument over a 1-week period in 8 subjects. RESULT: The mean MPOD levels measured by the MPS1000 and HFP were 0.40+/-0.18 and 0.47+/ 0.15, respectively, which were statistically significantly different by the paired t-test (t=3.95, P<0.001). A positive linear correlation was observed for MPOD at 0.5 degrees eccentricity between the two different instruments (r=0.4, P<0.001). The 95% limit of agreement was 0.07+/-0.35 as shown by Bland-Altman analysis. Intersessional repeatability, expressed as a coefficient of repeatability, was 0.26 for HFP and 0.18 for MPS1000. CONCLUSION: MPOD levels measured by MPS1000 were significantly higher as compared to that measured by the traditional HFP, suggesting that it is inappropriate to directly compare the MPOD levels measured by these two methodologies. PMID- 26850585 TI - [Alterations of retinal tissue induced by amyloid beta(1- 42) subretinal injection in mice]. AB - OBJECTIVE: To investigate the alterations of retinal tissue induced by OAbeta(1 42) subretinal injection in normal C57BL/6N mice. METHODS: Experimental study. One hundred and twenty C57BL/6N mice aged 8 weeks participated in this study. Among them, 60 eyes received subretinal injection of OAbeta(1-42); another 60 received double distilled water as control. The concentration of OAbeta(1-42) was 0.312 5 mmol/L. We took fundus photograph and autofluorescence, electroretinogram(ERG), haematoxylineosin staining of retinal paraffin sections, beta-galactosidase staining of neural retinal flatmounts, immunofluorescence of senescence marker P16INK4a of RPE/choroidal flatmounts, Western blot and RT-PCR of senescence relative cytokines IL-6, TGF-beta1 before and after the injection. The data were analyzed by independent sample t-test. RESULTS: Comparing with controls, 1 week post injection, the experimental group eyes had atrophied area with high autofluorescence site, and showed evident decrease in amplitudes of a wave (39.94+/-7.75)uV comparing with the controls (225.27+/-28.94)uV(t=12.45, P<0.001) in scotopia ERG, so did the amplitude of b wave (185.55+/-4.62)uV comparing with the controls (873.78+/-43.80)uV(t=27.06, P<0.001), retinal structures appeared significant loss of retinal thickness (t=75.13, P<0.001) along with hypo- or hyperpigmentation; the experimental eyes had high frequency of blue-green deposits in retinal beta-gal staining; the green fluorescence sites of RPE/choroidal flatmounts were clear and bright, indicating higher expression of P16INK4a in the nucleus; these results were the same till 8 weeks post operation. Western blot and RT-PCR vertified conspicuous increases in expression of TGF-beta1, IL-6 in retinas of experimental eyes compared with the control ones 1 week post injection. CONCLUSIONS: OAbeta(1-42) subretinal injection could induce visual function deficiency and retinal tissue senescence. All the manifestations were AMD-like retinopathy, which implied that Abeta(1-42) might be an essential clue in human AMD pathology. PMID- 26850586 TI - [The correlation between the concentrations of VEGF and PEDF and Ca2+-PKC signaling pathways in human retinal pigment epithelial cells cultured in vitro after exposuring to blue light]. AB - OBJECTIVE: To investigate the concentrations of vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), inositol triphosphate (IP3) and diacylglycerol (DAG) in human retinal pigment epithelium (RPE) cells after exposuring to blue light, and to explore the relationship with Ca2+-PKC signaling pathways, to evaluate the role of Ca2+-PKC signaling pathways of blue light irradiation induced apoptosis in RPE cells. METHODS: The fourth generation human RPE cells in vitro were exposured to blue light (2000+/-500 lux) for 6 hours, 24 hours prolongation of post-exposure culture. The concentrations of VEGF, PEDF, IP3 and DAG were assayed by enzyme linked immunosorbent assay (ELISA). Cells were randomly divided into 6 groups, group A (control), group B (exposure to blue light), group C (exposure to blue light+PMA), group D (exposure to blue light+Calphostin C), group E (exposure to blue light+Nifedipine), group F (exposure to blue light+Calphostin C+Nifedipine). Flow cytometry was used to detect the apoptosis rate of human RPE cells in A, B and F group. RESULTS: Comparing with group A (584.38+/-10.66), the concentration of VEGF in group B (700.70+/-5.88), group C (698.21+/-6.66) and group E (648.30+/-4.91) was higher, the difference was statistically significant (P=0.002, 0.002, 0.016). Comparing with group B (700.70+/-5.88), the concentration of VEGF in Group D (623.87+/ 3.12) and E (648.30+/-4.91) was lower (P=0.001, 0.002). Comparing with group A (75.96+/-1.70), the concentration of PEDF in Group B (71.82+/-1.67) and C (72.43+/-0.58) was lower (P=0.004, 0.011), but the concentration of PEDF in Group D (86.31+/-1.35) and E (93.72+/-1.24) was higher (P=0.000, 0.000). Comparing with group B (71.82+/-1.67), the concentration of PEDF in Group D (86.31+/-1.35) and E (93.72+/-1.24) was higher (P=0.000, 0.000). Comparing with group A (7.70+/-0.29), the ratio of VEGF to PEDF in Group B (9.85+/-0.34) and Croup C (9.64+/-0.02) was higher (P=0.008, 0.027) Comparing with group B, The ratio of VEGF to PEDF in Group D (7.23+/-0.08) and E (6.92+/-0.06) was lower (P=0.016, 0.015). Comparing with group A (108.42+/-0.75, 995.47+/- 13.61), the concentration of IP3 and DAG in Group B (117.24+/-1.06, 1070.10+/-10.07), C (137.12+/-2.71, 1046.40+/-7.90), D (139.17+/-1.40, 1041.13+/-9.76) and E (149.61+/-0.77, 1273.14+/-10.89) was higher, the difference was statistically significant (P=0.003, 0.007, 0.000, 0.000, 0.000, 0.000, 0.000, 0.000). Comparing with group B, the concentration of IP3 in Group C, D and E was higher (P=0.011, 0.000, 0.000). Comparing with group B, the concentration of DAG in Group C and D was lower (P=0.021, 0.007). Comparing with group B, the concentration of DAG in Group E was higher (P=0.000). Comparing with group A (10.27+/-1.88), the apoptosis rate of RPE cells in Group B(25.07+/-2.66) and F(19.37+/-3.23) was higher, the difference was statistically significant (P=0.001, 0.009). Comparing with group B (25.07+/-2.66), the apoptosis rate of RPE cells in Group F (19.37+/-3.23) was lower (P=0.038). CONCLUSIONS: (1) After exposuring to blue light, the concentrations of VEGF, IP3 and DAG are increased and the ratio of VEGF to PEDF is also increased and the concentration of PEDF is decreased in human RPE cells. (2) L-Type Calcium Channels and Ca2+-PKC signaling pathways may be regulate the concentrations of VEGF, PEDF, IP3 and DAG in RPE cells after exposuring to blue light by feedback regulation. (3) The application of Calphostin C combined with Nifedipine may be restrain the apoptosis of RPE cells after exposuring to blue light. PMID- 26850587 TI - [Efficacy of surgery on congenital nystagmus with convergence damping]. AB - OBJECTIVE: To evaluate the efficacy of surgery in the treatment of congenital nystagmus with convergence damping. METHODS: Retrospective and comparative case series. Eight patients diagnosed as congenital nystagmus with convergence damping at Beijing Children's Hospital between September 2010 and September 2012 were enrolled in this study. The ages were 9.5 (12, 6) years old, and follow-up was 9 (24, 6) months. All patients received prism induced convergence and the same surgery of bimedial rectus recession and bilateral rectus tenotomy. The best corrected visual acuity, the range of fusion and the nystagmus waveforms were analyzed before and after surgery. RESULTS: The range of fusion was -3.75+/-1.83 degrees to +19.38+/-3.16 degrees before surgery and -3.88+/-1.55 degrees to +19.00+/-3.02 degrees after surgery; there was no significant difference (t=0.24, P=0.82). The binocular visual acuity increased from 0.21+/-0.15 without convergence to 0.28+/-0.18 using convergence; there was significant difference (t=-4.43, P=0.00). The visual acuity was 0.32+/-0.20 after surgery, significantly different from that before surgery without convergence (t=-5.29, P=0.00), but not significantly different from that before surgery using convergence (t=-2.12, P=0.07). Patients had significant improvements in the frequency (t=3.28, 3.02, P<0.05) and intensity of the nystagmus waveforms when using convergence and postoperatively (t=3.27, 3.48; P<0.05), but there was no significant improvement in the amplitude of the waveforms (t=1.31, 1.57, 0.31, P>0.05). CONCLUSIONS: Surgery for congenital nystagmus with convergence damping can provide expectations for ocular motor and visual results. The range of fusion should be wide enough, and the effect of convergence on the frequency is greater than that on the amplitude. PMID- 26850588 TI - [Application of retinal oximeter in ophthalmology]. AB - Retinal oximeter is a new machine which has been used in the diagnose, treatment and research of several ophthalmic diseases for recent years. It allows ophthalmologists to gain retinal oxygen saturation directly. Therefore, retinal oximeter might be useful for ophthalmologists to understand ophthalmic diseases more deeper and clarify the impact of ischemia on retinal function. It has been reported in the literatures that retinal oximeter has potentially useful diagnostic and therapeutic indications in various eye diseases such as diabetic retinopathy, central retinal vein and artery occlusion, retinitis pigmentosa, glaucomatous optic neuropathy, et al. In this thesis, the application of retinal oximeter in ophthalmology is reviewed. PMID- 26850589 TI - [The application progress of three-dimensional cell culture technology in ophthalmology]. AB - Three-dimensional cell culture technology is a kind of technology that cultures the cells in a three-dimensional cultivation by using a kind of scaffold materials in vitro. Its advantage is that the vivo microenvironment simulating degrees of the three-dimensional culture technology is higher than that of the two-dimensional planar cell culture model, and the controllability is also higher than the animal experiment. In recent years, with the development of tissue engineering technology, a varietiy of the stent of biological materials also a fast development, which provided a favorable platform for three-dimensional cell culture technology. In ophthalmology, three-dimensional cell culture has been applied to the cornea, retina and the visual system development and other optic tumor researches. The objective of this paper is to making a review the application status of the three-dimensional cell culture technology in the basic research and clinical treatment in ophthalmology. PMID- 26850590 TI - [The research advance of measuring techniques on corneoscleral constitutive parameters]. AB - The occurrence and development of myopia and keratoconus is closely related to the changes of scleral and corneal biomechanical properties. The accurate measurement of biomechanical properties for corneoscleral tissure is very important on diagnosis of eye diseases, improvement of ocular operation, ocular biological parameter measurement and invention of ophthalmic instrument. Corneoscleral tissue, composed of bundles of compact and staggered collagen fiber and extracellular matrix, constitute the outer surface of the eyeball. The inhomogeneous distribution of the diameter, gap and amount of collagen fiber, makes its biomechanical characteristics really complex, characterized by nonlinear, viscoelastic, anisotropic, regional variation and age-related variation and etc. With the development of medical diagnostic technology, the importance of the ocular biomechanical property measurement is increasingly recognized. Nevertheless, measuring technology on ocular biomechanics properties are still not well understood by the majority of ophthalmologists. In order to facilitate the researchers to select a suitable measuring platform and method, the development of international corneoscleral biomechanical propertiy measuring technology was reviewed in this article. PMID- 26850591 TI - Edwardsiella piscicida-associated septicaemia in a blotched fantail stingray Taeniura meyeni (Mueller & Henle). PMID- 26850592 TI - Hypertension: is it a peri-operative or a public health problem? PMID- 26850594 TI - DNA methyltransferase 1, 3a, and 3b expression in hepatitis C associated human hepatocellular carcinoma and their clinicopathological association. AB - Identification of biomarker will obligate a substantial influence on various cancer management and treatment. We hypothesize that genetic/proteomic and epigenetic studies should be uncovering modifications which may be independently or jointly affect the expression of the genes that are involved in the progression of liver cancer (LC). For this purpose, we examined the effect of expressional changes of DNMTs on HCV infected LC of different genotypes. We found that both mRNA and protein expression levels of DNMT1, 3a, and 3b were upregulated in genotype 1b and 3a HCV infected patients as compared to control. However, DNMT3b mRNA levels did not change in genotypes 2a, 3, and 4, but were upregulated at the protein level by genotype 1b, 2a, and 3a. Furthermore, no significant changes were observed for DNMTs investigated in sample expressing the genotypes 5 and 6. Our findings suggest that HCV at least in part by altering DNMTs expression may play a significant role in HCC progression. PMID- 26850593 TI - Essential role of mitogen-activated protein kinases in IL-17A-induced MMP-3 expression in human synovial sarcoma cells. AB - BACKGROUND: The tumor cells were needed to rearrange the extracellular matrix (ECM) and reorganize their cytoskeleton to facilitate the cell motility during the tumor invasion. The proinflammatory cytokine interleukin-17A (IL-17A) is reported to up-regulate tumor invasiveness via ECM degradation by matrix metalloproteinases (MMPs). However the precise effects of IL-17A-dependent invasion remain to be characterized. The aim of this study was to elucidate the mechanisms underlying IL-17A-induced MMP-3 expression in the human synovial sarcoma cells HS-SY-II. METHODS: HS-SY-II cells were incubated with IL-17A. In some experiments, the cells were pre-incubated with an anti-IL-17 receptor polyclonal antibody (IL-17R Ab) or inhibitors for signaling cascade prior to addition of IL-17A. The expression of MMP-3 was determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and western blotting. IL-17R expression in HS-SY-II cells was assessed by immunofluorescence microscopy, while the phosphorylation of signaling molecules was measured by western blotting. RESULTS: IL-17A increased MMP-3 mRNA and protein expression. HS-SY-II cells express the IL-17R on their surface and blockage of IL-17A-IL-17R binding by IL 17R Ab suppressed IL-17A-mediated induction of MMP-3. IL-17A induced the phosphorylation of three components of the mitogen-activated protein kinase (MAPK) pathway including extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAPK, and c-Jun NH2-terminal kinase (JNK). Pre-treatment of the cells with inhibitors of ERK1/2, p38 MAPK, and JNK attenuated the IL-17A-induced phosphorylation of activator protein-1 (AP-1) subunits and the expression of MMP 3 mRNA. CONCLUSION: Our results indicate an essential role for MAPKs in the induction of MMP-3 in synovial sarcoma cells, through AP-1 activation. PMID- 26850595 TI - MicroRNA-873 mediates multidrug resistance in ovarian cancer cells by targeting ABCB1. AB - Ovarian cancer is commonly treated with cisplatin and paclitaxel combination chemotherapy; however, ovarian cancer cells often develop resistance to these drugs. Increasingly, microRNAs (miRNAs) including miR-873 have been implicated in drug resistance in many cancers, but the role of miR-873 in ovarian cancer remains unknown. MTT cell viability assays revealed that the sensitivities of ovarian cancer lines to cisplatin and paclitaxel increased following transfection with miR-873 (P < 0.05). After predicting the miR-873 binding region in the 3' untranslated region of ABCB1, dual-luciferase reporter assay confirmed this prediction. RT-PCR and Western blotting revealed that MDR1 expression was significantly downregulated after transfection with miR-873 and upregulated after transfection with anti-miR-873 at both mRNA and protein levels compared to negative controls (P < 0.05). Experiments in a mouse xenograft model confirmed that intratumoral administration of miR-873 could enhance the efficacy of cisplatin in inhibiting tumor growth in ovarian cancer in vivo (P < 0.05). ABCB1 overexpression reduced sensitivities of ovarian cancer lines OVCAR3 and A2780 to cisplatin and paclitaxel, which can be reversed by miR-873 mimic transfection (P < 0.05). In summary, we demonstrated that overexpression of miR-873 increased the sensitivity of ovarian cancer cells to cisplatin and paclitaxel by targeting MDR1 expression. Our findings suggest that combination therapies with chemotherapy agents and miR-873 may suppress drug resistance in ovarian cancer. PMID- 26850596 TI - The effect of antisense inhibitor of miRNA 106b~25 on the proliferation, invasion, migration, and apoptosis of gastric cancer cell. AB - Accumulating data has demonstrated that miRNA 106b~25, which are composed of the highly conserved miRNA 106b, miRNA 93, and miRNA 25, play carcinogenic roles in cancers. We investigated the expression of miRNA 106b~25 in gastric cancer cells (SGC 7901, MGC 803, BGC 823) and normal gastric epithelial cell then inhibited miRNA 106b~25 expression via transiently transfecting their antisense inhibitor. After miRNA 106b~25 cluster was inhibited, MTT, Scratch test, Transwell invasion test, and flow cytometry were applied to investigate the proliferation, invasion, migration, cell cycle, and apoptosis of gastric cancer cell. The expression of miRNA 106b, miRNA 93, and miRNA 25 in gastric cancer cells SGC 7901, MGC 803, and BGC 823 was significantly higher than in gastric epithelial cell GES-1. The most significant suppression of miRNA 106b~25 expressions can be detected in MGC 803 cell after transiently transfecting their antisense inhibitors. So, MGC 803 cell was selected as our research object. After inhibiting miRNA 106b and miRNA 93 respectively and combined, the proliferation, migration, and invasion of gastric cancer cell MGC 803 were significantly suppressed. The most significant suppression was observed in combined inhibiting group. After miRNA 106b~25 cluster was inhibited respectively or combined, more gastric cancer cells were arrested in the G0G1 phase. However, there was no statistical difference in comparing with control groups. While the percentages of apoptotic cells increased after miRNA 106b~25 cluster was inhibited, the statistical difference was detected only in combined inhibiting group. Inhibiting miRNA 106b~25 cluster via transfecting antisense inhibitor can influence biological behavior of gastric cancer cell. PMID- 26850597 TI - Males seropositive for hepatitis B surface antigen are at risk of lower bone mineral density: the 2008-2010 Korea National Health and Nutrition Examination Surveys. AB - BACKGROUND: Hepatic osteodystrophy has been reported in patients with various chronic liver diseases, including liver cirrhosis. However, it has not been well investigated in patients with hepatitis B virus infection. The aim of this study was to investigate the association between hepatitis B surface antigen (HBsAg) seropositivity and bone mineral density (BMD) in a population representative of normal Koreans. METHODS: Subjects with both HBsAg and BMD levels examined during the 2008-2010 Korea National Health and Nutrition Examination Surveys were included. HBsAg-seropositive (+) subjects were compared with those who were HBsAg seronegative (-). BMD was measured at the lumbar spine and femur by dual-energy X ray absorptiometry. Multivariable logistic regression was performed for BMD . RESULTS: In total, 11,306 participants were included in this study, among which 423 (3.7 %) were HBsAg(+): 153 premenopausal female (3.4 %), 83 postmenopausal female (3.5 %), and 187 male (4.2 %). Multivariable logistic regression analysis adjusted for age and body mass index showed that HBsAg(+) male had significantly lower BMD of the femoral neck than HBsAg(-) male (0.810 +/- 0.009 vs. 0.827 +/- 0.002 g/cm(2), p = 0.035). Further adjustment for waist circumference, smoking, drinking, exercise, income, occupation, and vitamin D levels showed that HBsAg(+) male had significantly lower BMD of the femur neck (0.810 +/- 0.010 vs. 0.831 +/- 0.002 g/cm(2), p = 0.032) and lumbar spine (0.953 +/- 0.011 vs. 0.974 +/- 0.003 g/cm(2), p = 0.049) than HBsAg(-) male. CONCLUSIONS: HBsAg seropositivity was significantly associated with lower BMD in male. Future long-term prospective studies investigating bone turnover markers and hormones are needed to better understand the pathophysiology and clinical significance of chronic hepatitis B virus-related hepatic osteodystrophy. PMID- 26850598 TI - First Report of a Dominantly Inherited beta-Thalassemia Caused by a Novel Elongated beta-Globin Chain. AB - A distinct set of mutations on the beta-globin gene leads to dominantly inherited beta-thalassemia (beta-thal) that is associated with a disease phenotype in a single mutant copy. We described molecular and hematological characteristics of a novel elongated beta-globin chain in combination with a known hemoglobin (Hb) variant (N-Baltimore or HBB: c.286A>G) in cis. The highly unstable Hb variant caused typical features of beta-thal major (beta-TM) or beta-thal intermedia (beta-TI) in two members of a family depending on their alpha-globin genotypes. The beta mutant allele of the mother was transmitted in an autosomal dominant fashion to her daughter. They resemble severe forms of beta-thal due to ineffective erythropoiesis. Taken together with previously published data, this result indicates that a dominant form of beta-thal should be regarded as a phenotypic term of hemoglobinopathies caused by beta chain variants that are highly unstable. PMID- 26850599 TI - [Biomedical research thought in French: New year, new concepts]. PMID- 26850600 TI - [Early environments, early origins of health and disease]. PMID- 26850601 TI - [Not Available]. PMID- 26850602 TI - [Developmental origin of health and adult diseases (DOHaD): evolution of a concept over three decades]. AB - In the 1980s, D. Barker and his team proposed the hypothesis of a fetal origin of adult diseases. The concept subsequently evolved into the developmental origins of health and diseases. Progresses in various domains such as social epidemiology, neuroscience, toxicology have contributed to establish the early years of life as a key period for future health. Finally, epigenetics has provided biological plausibility to long-term programming of health by early exposures. The convergence of all these currents has led to conceptualize human health in a complex and dynamic continuum, the Lifecourse Health Development, beginning in the prenatal period and covering the whole life. Many animal models have been developed to try to unravel the mechanisms involved. Their contributions are described in this paper with the example of type 2 diabetes. PMID- 26850603 TI - [DOHaD: epidemiological researches]. AB - Epidemiological researches in the field of DOHaD are in favor of a role of early environment, including chemical (pesticides), physical (air pollution), nutritional or psychosocial environment, on child and adult health. Disentangling the different factors of environment that may affect health, especially over time, and identifying critical periods of exposure remains a major challenge. The biological mechanisms involved remain elusive in human beings. Nevertheless, it seems that whatever the nature of the exposure, epigenetic mechanisms are currently discussed to explain how the environment may alter biological systems over time. PMID- 26850604 TI - [The new paradigm of the developmental origin of health and diseases (DOHaD)- Epigenetics and environment: evidence and missing links]. AB - According to the new paradigm of the Developpemental Origins of Health and Disease (DOHaD), the environmental factors to which an individual is exposed throughout his life can leave an epigenetic footprint on the genome. A crucial period is the early development, where the epigenome is particularly sensitive to the effects of the environment, and during which the individual builds up his health capital that will enable him to respond more or less well to the vagaries of life. The research challenge is to decipher the modes of action and the epigenetic mechanisms put into play by environmental factors that lead to increased disease susceptibility or resilience. The challenge for health is to translate these scientific discoveries into action through, among others, the establishment of preventive recommendations to slow down the growing incidence of non communicable diseases. PMID- 26850605 TI - [Epigenetics in transgenerational responses to environmental impacts: from facts and gaps]. AB - The existence of non-genetic and non-cultural mechanisms that transfer information on the memory of parental exposures to various environments, determining the reactivity of the following generations to their environments during their life, are of growing interest. Yet fundamental questions remain about the nature, the roles and relative importance of epigenetic marks and processes, non-coding RNAs, or other mechanisms, and their persistence over generations. A model incorporating the various transmission systems, their cross talks and windows of susceptibility to the environment as a function of sex/gender of parent and offspring, has yet to be built. PMID- 26850606 TI - [Developmental and environnemental origin of male infertility: role of endocrine disruptors]. AB - Human and wildlife exposure to chemicals is thought to be extensive and particularly to endocrine-disrupting chemicals (EDCs) suspected to alter male reproductive tract. When the exposure occurs during perinatal period (fetal, neonatal periods or puberty) the reproductive health alterations are irreversible suggesting a developmental origin to male infertility. This concept is supported by numerous epidemiologic and experimental studies. This review summarizes the data concerning the epigenetic mechanisms (DNA methylation, chromatin remodelling, small-non coding RNAs) involved in developmentally-induced male infertility. These data open potentially to new diagnosis tools and new trails to assessment of EDCs risks. PMID- 26850607 TI - [Impact of in utero exposure to pollutants on metabolic health in adults]. AB - Obesity is a major public health problem because it is a risk factor for metabolic disorders including type 2 diabetes and cardiovascular disorders. Notably, pollutants endowed with endocrine disrupting activities have been charged to contribute to the etiology of obesity and type 2 diabetes, especially if exposure occurs during the early life shown to be a highly vulnerable window of time. An overview on endocrine disrupters in relation with the obesogen and metabolic disruption hypothesis is presented. Convincing data support the plausibility of such hypothesis. They also highlight the limits of the current threshold model used in risk assessment which focused on single chemicals and does not take into account potential effects of mixtures containing pollutants at environmental doses, e.g. the real life exposure. Certainly, the principle of precaution should guide the making of decisions especially when considering early life exposure. PMID- 26850608 TI - [DOHaD and pre- or peri-conceptional programming]. AB - The pre- and peri-conceptional periods (before and just after fertilization, until the blastocyst stage) are critical in the context of the Developmental Origins of Health and Disease (DOHaD). Maternal in vivo environment, in particular nutrition, can disturb the apposition of epigenetic marks throughout gametogenesis, fertilization and the first steps of embryonic development, which are times during which major epigenetic changes take place. The in vitro environment, in the case of assisted reproduction techniques, also affects epigenetic marks. Whilst the embryo is a target of these changes, female and male gametes are both target and vector of these epigenetic changes, thus leading to multigenerational effects. Long term consequences on the phenotype of offspring vary according to the sex of the vector parent, the sex of the individual and the generation. PMID- 26850609 TI - [Impact of maternal obesity and diabetes on placental function]. AB - Located at the feto-maternal interface, the placenta is involved in exchange, endocrine and immune functions, which impact fetal development. In contact with the maternal environment, this organ is sensitive to metabolic disorders as over nutrition, obesity or diabetes. The alteration of blood parameters associated with these pathologies affects placental histology, vascularization and nutrient transfers and, according to the types of troubles, induces local inflammation or hypoxia. These placental changes lead to disturbance of development and fetal growth, which increase the risk of pathologies in offspring in adulthood. The placenta thus appears as a crucial player in the fetal programming. PMID- 26850610 TI - [DOHaD: long-term impact of perinatal diseases (IUGR and prematurity)]. AB - The first epidemiological studies showing a link between low birth weight and chronic diseases in adults did not distinguish the origins of low birth weight. A low birth weight may be the result of a premature birth. It can also be caused by an intrauterine growth restriction (IUGR). A child can be both preterm and IUGR. It is clear now that prematurity is an independent risk factor for programming chronic adult diseases. However, unlike adults born IUGR, adults born prematurely do not have an increased risk to develop metabolic syndrome (dyslipidemia or obesity). An increased risk of neurodevelopmental and psychiatric morbidity and hypertension is found after a premature birth. Mechanisms of chronic diseases programming are multiple: they involve both the cause of prematurity and IUGR such as infection / inflammation or placental insufficiency, but also consequences for therapeutic or nutritional strategies needed to support these children. This chapter describes the possible prevention of perinatal programming of noncommunicable diseases. PMID- 26850611 TI - [Maternal nutritional manipulations: is the adipose tissue a key target of programming?]. AB - The nutritional imprinting, whose mechanisms remain still dark and which seem to continue through the following generations, highlight the key-role of the inadequacy between the pre-and postnatal nutritional environment and the programming of the obesity. PMID- 26850612 TI - [The sensory and nutritional experience of parents guide offsprings' feeding behavior]. AB - Eating behavior is strongly regulated by intrinsic physiological factors and largely influenced by the individual and cultural environments. Excessive food intake and sedentary lifestyle are the main reasons for the global epidemic of obesity. The influence of family background on eating habits makes no doubt but the fact that the nutritional, metabolic and hormonal status of the parents before conception, and of the mother during gestation and lactation, may influence the child's future eating behavior is an innovative concept that opens the way for preventive policies. In the last decades, research on human cohorts and animal models have targeted biological mechanisms (neuroanatomical, epigenetic) that give some clues on how eating behavior can be formatted by early nutrition and related sensory experience. PMID- 26850613 TI - [Early life stressful experiences and neuropsychiatric vulnerability: evidences from human and animal models]. AB - The human newborn is highly dependent on parental care for its survival but also for the healthy development of its brain. A large body of literature demonstrates the impact of early life adversity, even during the prenatal period, on the adult's health. The susceptibility to neuropsychiatric diseases is often potentiated by early stress. If there is an agreement that a critical developmental period exists, the mechanisms underlying the long term effects of early life adversity are still poorly understood. Recent studies in animals highlight the involvement of epigenetic processes in the transmission of such vulnerabilities, notably via modifications in germ cells, which can be transmitted in the next generations. PMID- 26850614 TI - [DOhaD and epigenetic information: societal challenges]. AB - The concept of the developmental origins of health and disease (DOHaD) alters our understanding of what constitutes "health" or "disease" intended as chronic, non communicable diseases, which develop over the life course in high income and emerging countries. It implies a change in paradigm forming a basis for prevention policies across the globe. It also impacts psychological, social, economic, ethical and legal sciences. In line with the unanticipated underpinning epigenetic mechanisms are also the social issues (including public policies) that could be produced by the knowledge related to DOHaD that opens a wide field of inquiry. The information unveiled by epigenetics coupled with information on lifestyle including during the development phase, is of unforeseen nature, raising issues of different nature. Therefore it requires specific attention and research, and a specific support by a pluridisciplinary reflection since the very beginning of its production, to anticipate the questions that might be raised in the future. PMID- 26850615 TI - [Youyou Tu, from Mao Zedong to the Nobel Prize]. PMID- 26850616 TI - [A Nobel Prize in Medicine 2015 for tropical countries: ivermectin, an antiparasitic drug undeniable against filariasis]. PMID- 26850617 TI - [A Nobel Prize for DNA repair]. AB - This year's Nobel Prize for chemistry recognizes the seminal contributions of three researchers who discovered the existence and the basic mechanisms of DNA repair: base excision repair, mismatch repair, and nucleotide excision repair. They have since been joined by many scientists elucidating diverse aspects of these complex mechanisms that now constitute a thriving research field with many applications, notably for understanding oncogenesis and devising more effective therapies. PMID- 26850618 TI - [The man who blew-up the lock of the anti-tumor adaptive immune response]. PMID- 26850619 TI - [Lasker award 2015: spotlight on DNA repair]. PMID- 26850620 TI - [In the beginning was the Word]. PMID- 26850621 TI - Effects of the exposure to atrazine on bone development of Podocnemis expansa (Testudines, Podocnemididae). AB - The use of pesticides is a widely spread practice in Brazilian agriculture, and dispersion of these substances is an important factor for the fauna and flora. Atrazine is an endocrine disruptor in the xenoestrogen class that is used worldwide in agricultural practices. In Brazil, its use is permitted in several crops. Podocnemis expansa is a representative of the Testudines order that is the largest freshwater reptile of South America. Its distribution enables it to get in contact with molecules that are commonly used as pesticides, which may cause deleterious effects in target populations. In order to evaluate the possible effects of the exposure to atrazine on bone ontogeny of this species, eggs were artificially incubated in sand moistened with water contaminated with atrazine at concentrations equal to 0, 2, 20 or 200 MUg/L. Embryos were collected throughout incubation and submitted to diaphanization of soft tissues with potassium hydroxide (KOH); bones were stained with Alizarin red S and cartilages by Alcian blue. Embryos were evaluated for the presence of abnormalities during the different stages of pre-natal development of skeletal elements. No effect of atrazine was observed on bone development during the embryonic phase in P. expansa individuals, in the conditions of this study. PMID- 26850622 TI - No effect of Zn-pollution on the energy content in the black garden ant. AB - Social insects may display a response to environmental pollution at the colony level. The key trait of an ant colony is to share energy between castes in order to maintain the existing adult population and to feed the brood. In the present study we calorimetrically measured the energy content per body mass (J/mg) of adults and pupae of workers, males and females of the black garden ant Lasius niger. The ants were sampled from 37 wild colonies originating from 19 sites located along the metal pollution gradient established in a post-mining area in Poland. The cost of metal detoxification seen as a possible reduction in energy content with increasing pollution was found neither for pupae nor adults. However, a considerable part of variance in energy content is explained by belonging to the same colony. These findings stress the importance of colony specific factors and/or the interaction of these factors with specific site in shaping the response of ants to metal-pollution stress. Colony-related factors may constrain possible selfish decisions of workers over energy allocation in workers and sexual castes. PMID- 26850624 TI - Can an internet-based program for the prevention and early intervention in eating disorders facilitate access to conventional professional healthcare? AB - BACKGROUND: The majorities of individual suffering from eating disorders do not seek or receive adequate professional treatment. Internet-based approaches promise to facilitate access to conventional healthcare by providing an easy access, low-threshold contact. AIM: The current study investigated whether an Internet-based program for the prevention and early intervention for eating disorders (ProYouth) may contribute to the actual and intended uptake of professional care. Characteristics of individuals who seek help are explored as well as barriers to help-seeking. METHOD: The sample included 453 ProYouth participants who were surveyed three months after registration. Actual help seeking behavior, intended help-seeking, potential help-seeking, and barriers to help-seeking were assessed. RESULTS: Within three months of participation, 43 individuals (9.5%) took up treatment, 32 (7.8%) intended to start treatment, and 163 (43.1%) of the remaining reported that they would seek professional help in case of need (potential help-seeking). Approximately 50% of (potential) help seekers stated that participation in ProYouth has changed their attitude towards help-seeking. Mental health literacy and shame/stigma were the most frequently mentioned barriers. CONCLUSIONS: This is the first study indicating that an online program for prevention and early intervention may serve as facilitator in accessing conventional healthcare. PMID- 26850623 TI - Cone beam CT evaluation of mandibular molar root canal morphology in a Turkish Cypriot population. AB - OBJECTIVES: Microorganisms in untreated or overlooked root canals can cause endodontic failure or infection and inflammation. Therefore, clinicians should familiarize themselves with patient's root canal anatomy and morphology. The objective of this retrospective study was to analyze and characterize mandibular root canal morphology using cone beam computed tomography (CBCT) in a Turkish Cypriot population. MATERIALS AND METHODS: This cross-sectional study consisted of retrospective evaluation of CBCT scans from 272 adult patients (aged 16-80 years). The number of roots and canals and the canal configuration in each root were evaluated using Vertucci's classification. The incidence of additional roots and of C-shaped canals in the mandibular first and second molars was also noted. Pearson chi-square tests were performed to analyze canal configurations, laterality, and gender (p <= 0.05). RESULTS: For the female and male patients, 94.5 and 94.4 % of the mandibular first and 96.7 and 97.2 % of the mandibular second molars had two roots, respectively. In females, 4.4 % of mandibular first molars had three roots versus 2.7 % of mandibular first molars in male patients. Type IV was the most prevalent canal configuration regardless of the gender (female 61.3 % and male 64.2 %) in the mesial roots. No statistically significant differences according to gender or laterality were found in the incidence of additional canals for either maxillary first or second molars. CONCLUSIONS: Type IV was the most prevalent canal configuration of both the mandibular first and second molar teeth. There was a low prevalence of three-rooted mandibular molars in this particular population. CLINICAL RELEVANCE: The current study is the first of its kind to include a Turkish Cypriot population and, thus, provides baseline data for these patients regarding appropriate root canal treatments. PMID- 26850625 TI - [Early lung disease in infants with cystic fibrosis. Diagnostic tools and possible therapeutic pathways]. AB - The lungs of infants with cystic fibrosis (CF) have been considered to be normal at birth. However, recent data indicates that this is unlikely to be true in most cases. Animal CF-models developed in the early 2000s have shown that constitutional airway narrowing may be present at birth, and is associated with both functional and structural abnormalities. Longitudinal birth cohort studies have shown that 25 % of CF infants followed in specialized centers, while being asymptomatic, showed decreased lung function at 3months of age. Air trapping was present in 68 % and bronchiectasis in 28 % of patients at the same age. The presence of neutrophil elastase in the bronchoalveolar lavage at 3months of age tripled the risk of bronchiectasis at the age of 3years. Currently available tools such as infant pulmonary function tests (both the jacket and multiple breath washout) as well as high-resolution volume controlled chest-computed tomography or functional magnetic resonance imaging will facilitate early intervention trials in the very near future. The role of such tools for the routine follow-up of patients, and the ability of early therapeutic interventions to alter the natural history of CF-lung disease should soon be established. PMID- 26850627 TI - Activation of context-specific attentional control sets by exogenous allocation of visual attention to the context? AB - Different contexts with high versus low conflict frequencies require a specific attentional control involvement, i.e., strong attentional control for high conflict contexts and less attentional control for low conflict contexts. While it is assumed that the corresponding control set can be activated upon stimulus presentation at the respective context (e.g., upper versus lower location), the actual features that trigger control set activation are to date not described. Here, we ask whether the perceptual priming of the location context by an abrupt onset of irrelevant stimuli is sufficient in activating the context-specific attentional control set. For example, the mere onset of a stimulus might disambiguate the relevant location context and thus, serve as a low-level perceptual trigger mechanism that activates the context-specific attentional control set. In Experiment 1 and 2, the onsets of task-relevant and task irrelevant (distracter) stimuli were manipulated at each context location to compete for triggering the activation of the appropriate control set. In Experiment 3, a prior training session enabled distracter stimuli to establish contextual control associations of their own before entering the test session. Results consistently showed that the mere onset of a task-irrelevant stimulus (with or without a context-control association) is not sufficient to activate the context-associated attentional control set by disambiguating the relevant context location. Instead, we argue that the identification of the relevant stimulus at the respective context is a precondition to trigger the activation of the context associated attentional control set. PMID- 26850628 TI - Cardiac CT assessment of left ventricular mass in mid-diastasis and its prognostic value. AB - AIMS: To determine the influence of cardiac motion on measurements of left ventricular (LV) mass obtained with 64-slice computed tomography (CT) and to elucidate the prognostic value of LV mass on major adverse cardiac events (MACE) and all-cause mortality. Increased LV mass has been linked with MACE. Although Cardiac CT allows measurement of LV anatomy, it is susceptible to motion artefacts often requiring image acquisition during diastasis. There is a need to understand variability in LV mass measurements across phases of the cardiac cycle, and whether mid-diastolic measurements have prognostic value. METHODS AND RESULTS: The study comprised two equally sized cohorts of patients that had undergone retrospectively gated cardiac CT: patients who had MACE and/or all cause death at follow-up and a matched (age, sex, and risk factors) event-free cohort. LV mass was measured at mid-diastole, end-diastole, and end-systole. Correlation and agreement between phases were determined. The incremental value of mid-diastolic hypertrophy (LVH) over the National Cholesterol Education Programme (NCEP) risk was performed for LV mass indices normalized to body surface area (LVMIBSA) or weight (LVMIWeight). Of 166 patients, 31.3% experienced MACE and 28.9% died of any cause (follow-up 22.9 +/- 13.4 months). LV mass at all cardiac phases were strongly correlated (r > 0.94). Mean mid-diastolic LVMIBSA was higher in the cohort with events (93.7 vs. 80.7 g/m2, P= 0.008) as was LVMIWeight (2.26 vs. 1.88 g/kg, P = 0.001). LVMIBSA and LVMIWeight had prognostic value incremental to NCEP with 1.85 and 2.47 hazard ratios, respectively. CONCLUSIONS: Measurement of LV mass can be obtained by cardiac CT images obtained at mid-diastasis. LV mass measurements obtained at mid-diastasis have prognostic value. PMID- 26850626 TI - Myocardial triglyceride content at 3 T cardiovascular magnetic resonance and left ventricular systolic function: a cross-sectional study in patients hospitalized with acute heart failure. AB - BACKGROUND: Increased myocardial triglyceride (TG) content has been recognized as a risk factor for cardiovascular disease. However, its relation with cardiac function in patients on recovery from acute heart failure (HF) remains unclear. In this cross-sectional study, we sought to investigate the association between myocardial TG content measured on magnetic resonance spectroscopy ((1)H-MRS) and left ventricular (LV) function assessed on cardiovascular magnetic resonance (CMR) in patients who were hospitalized with HF. METHODS: A total of 50 patients who were discharged after hospitalization for acute HF and 21 age- and sex matched controls were included in the study. Myocardial TG content and LV parameters (function and mass) were measured on a 3.0 T MR scanner. Fatty acid (FA) and unsaturated fatty acid (UFA) content was normalized against water (W) using the LC-Model algorithm. The patient population was dichotomized according to the left ventricular ejection fraction (LVEF, <50% or >= 50%). RESULTS: H-MRS data were available for 48 patients and 21 controls. Of the 48 patients, 25 had a LVEF <50% (mean, 31.2%), whereas the remaining 23 had a normal LVEF (mean, 60.2%). Myocardial UFA/W ratio was found to differ significantly in patients with low LVEF, normal LVEF, and controls (0.79% vs. 0.21% vs. 0.14%, respectively, p = 0.02). The myocardial UFA/TG ratio was associated with LV mass (r = 0.39, p < 0.001) and modestly related to LV end-diastolic volume (LVEDV; r = 0.24, p = 0.039). We also identified negative correlations of the myocardial FA/TG ratio with both LV mass (r = -0.39, p < 0.001) and LVEDV (r = -0.24, p = 0.039). CONCLUSIONS: As compared with controls, patients who were discharged after hospitalization for acute HF had increased myocardial UFA content; furthermore, UFA was inversely related with LVEF, LV mass and, to a lesser extent, LVEDV. Our study may stimulate further research on the measure of myocardial UFA content by (1)H-MRS for outcome prediction. TRIAL REGISTRATION: ClinicalTrial.gov: NCT02378402 . Registered 27/02/2015. PMID- 26850629 TI - The relationship between work stress and work ability among power supply workers in Guangdong, China: a cross-sectional study. AB - BACKGROUND: Faced with the challenge of population aging, a prolonged working life is increasingly important in today's society. Maintaining work ability of employees is one of the effective ways to cope with the challenges to sustainability of the workforce presented by population aging. Researchers have shown ongoing interest in exploring the determinants of restricted work ability. The aim of this study was to evaluate the effects of work stress on work ability among power supply workers in Guangdong, China. METHODS: A cross-sectional study was conducted among power supply workers during August 2014 to September 2014. A total of 805 subjects were enrolled in the study. Work stress was assessed by the Job Content Questionnaire and the Effort Reward Imbalance Questionnaire. Work ability was assessed by the Work Ability Index (WAI). The structural equation model was applied to test the relationship between different work stress components and work ability simultaneously using the Job Demands-Resources model as a framework. RESULTS: Job resources (measured by job control, reward and social support) were positively and directly associated with work ability (beta = 0.70, P < 0.001). The association between job demands and work ability was also statistically significant (beta = -0.09, P = 0.030). In addition, the findings also supported previous studies in that job demands were correlated with job resources (beta = -0.26, P < 0.001). CONCLUSIONS: Our findings suggest that decision makers and health care providers should consider increasing job resources available to power supply workers. Consideration of organizational changes related to the design of the job task also would be useful to improve the employees' work ability. PMID- 26850631 TI - Technical and clinical accuracy of three blood glucose meters: clinical impact assessment using error grid analysis and insulin sliding scales. AB - AIMS: Manufacturers of point-of-care testing (POCT) glucose systems must adhere to International Organisation for Standardisation (ISO) 15197 performance standards, a tightened version of which becomes mandatory in May 2016. Using methods deviating from the evaluation requirements of ISO 15197, we investigated the accuracy and clinical utility of three glucose testing systems. METHODS: Whole blood glucose was measured on 62 EDTA-preserved samples with each system followed by plasma glucose determination with a laboratory hexokinase method. Technical accuracy was assessed using linear regression, Bland-Altman plots and bias. Clinical utility was evaluated using consensus error grid analysis and insulin dosing algorithms. RESULTS: The correlation coefficient of the glucose measuring devices with the comparator method was between 0.979 and 0.993 (n=61). Bias against the reference method was +0.7-+4.4%. The FreeStyle Lite (0.7+/-4.4%) and ACCU-CHEK Aviva (1.3+/-7.3%) systems had the least bias to the reference. Error grid analysis depicts all meters to be clinically accurate, with all results falling within Zones A and B. CONCLUSIONS: Conformite Europeene-marked devices are presumed to have adequate accuracy, but postmarket evaluations are imperative to assess total system accuracy and whether regulatory targets are achieved. PMID- 26850630 TI - Advances in immunotherapy for melanoma. AB - In recent years, the introduction and Federal Drug Administration approval of immune checkpoint inhibitor antibodies has dramatically improved the clinical outcomes for patients with advanced melanoma. These antagonist monoclonal antibodies are capable of unleashing dormant or exhausted antitumor immunity, which has led to durable complete and partial responses in a large number of patients. Ipilimumab targets the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) receptor. Nivolumab and pembrolizumab target programmed cell death protein 1 (PD-1) receptors and have proven to be superior to ipilimumab alone. The combination of ipilimumab and nivolumab has yielded higher response rates, greater tumor shrinkage, and longer progression-free survival than either monotherapy alone. As other promising immunotherapies for melanoma proceed through clinical trials, future goals include defining the role of immune checkpoint inhibitors as adjuvant therapy, identifying optimal combination strategies, and developing reliable predictive biomarkers to guide treatment selection for individual patients. PMID- 26850633 TI - US needs $1.1bn to treat opioid addiction. PMID- 26850632 TI - The presence of fructosamine in human aortic valves is associated with valve stiffness. AB - AIMS: Human heart valves are prone to glycation, a fundamental process of ageing. The aim of this study was to establish the relationship between fructosamine formation and the mechanical properties of human aortic valves. METHODS: 67 patients (age: 76+/-8 years) diagnosed with an aortic valve stenosis, who underwent an aortic valve replacement were enrolled. Fructosamine and calcium concentrations in aortic valves were determined. Using a transthoracic Doppler echocardiography, aortic valve orifice area and transvalvular pressure gradients were measured. In a subgroup of 32 patients, the aortic valve orifice area was sufficient to carry out mechanical testing on a LFPlus Universal material tester. An in vitro removal of fructosamine of the valve was initiated using ATP dependent fructosamine 3-kinase (FN3K). RESULTS: A significant correlation was found between the aortic valve fructosamine concentration and the calculated aortic valve orifice area: Y (aortic valve orifice area, mm(2))=1.050-0.228X (aortic valve fructosamine concentration, umol/g valve) (r=-0.38). A significantly higher calcium concentration was measured in the aortic valves of diabetics in comparison with those of non-diabetics. A multiple regression analysis revealed that the presence of diabetes mellitus and aortic valve fructosamine concentration were the main predictors of the extensibility of the aortic valves. In the in vitro deglycation study, a significant lower aortic valve fructosamine concentration was detected after treatment with FN3K. This resulted in an increased flexibility of the aortic valves. CONCLUSIONS: Although no direct causativeness is proven with the presented results, which just show an association between fructosamine, the effect of FN3K and aortic valve stiffness, the present study points for the first time towards a possible additional role of the Amadori products in the biomechanical properties of ageing aortic valves. PMID- 26850634 TI - Cohen Kadosh, R., & Dowker, A. (Eds.). The Oxford Handbook of Numerical Cognition. PMID- 26850636 TI - Confirmation of brainstem death. PMID- 26850635 TI - IgA1 Protease Treatment Reverses Mesangial Deposits and Hematuria in a Model of IgA Nephropathy. AB - IgA nephropathy (IgAN), characterized by mesangial IgA1 deposits, is a leading cause of renal failure worldwide. IgAN pathogenesis involves circulating hypogalactosylated IgA1 complexed with soluble IgA Fc receptor I (sCD89) and/or anti-hypogalactosylated-IgA1 autoantibodies, but no specific treatment is available for IgAN. The absence of IgA1 and CD89 homologs in the mouse has precluded in vivo proof-of-concept studies of specific therapies targeting IgA1. However, the alpha1KI-CD89Tg mouse model of IgAN, which expresses human IgA1 and human CD89, allows in vivo testing of recombinant IgA1 protease (IgA1-P), a bacterial protein that selectively cleaves human IgA1. Mice injected with IgA1-P (1-10 mg/kg) had Fc fragments of IgA1 in both serum and urine, associated with a decrease in IgA1-sCD89 complexes. Levels of mesangial IgA1 deposits and the binding partners of these deposits (sCD89, transferrin receptor, and transglutaminase 2) decreased markedly 1 week after treatment, as did the levels of C3 deposition, CD11b(+) infiltrating cells, and fibronectin. Antiprotease antibodies did not significantly alter IgA1-P activity. Moreover, hematuria consistently decreased after treatment. In conclusion, IgA1-P strongly diminishes human IgA1 mesangial deposits and reduces inflammation, fibrosis, and hematuria in a mouse IgAN model, and therefore may be a plausible treatment for patients with IgAN. PMID- 26850637 TI - CD57 in human natural killer cells and T-lymphocytes. AB - The CD57 antigen (alternatively HNK-1, LEU-7, or L2) is routinely used to identify terminally differentiated 'senescent' cells with reduced proliferative capacity and altered functional properties. In this article, we review current understanding of the attributes of CD57-expressing T-cells and NK cells in both health and disease and discuss how this marker can inform researchers about their likely functions in human blood and tissues in vivo. While CD57 expression on human lymphocytes indicates an inability to proliferate, these cells also display high cytotoxic potential, and CD57(pos) NK cells exhibit both memory-like features and potent effector functions. Accordingly, frequencies of CD57 expressing cells in blood and tissues have been correlated with clinical prognosis in chronic infections or various cancers and with human aging. Functional modulation of senescent CD57(pos) T-cells and mature CD57(pos) NK cells may therefore represent innovative strategies for protection against human immunological aging and/or various chronic diseases. PMID- 26850638 TI - Identification of Inhibitors of Pseudomonas aeruginosa Exotoxin-S ADP Ribosyltransferase Activity. AB - The gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen associated with drug resistance complications and, as such, an important object for drug discovery efforts. One attractive target for development of therapeutics is the ADP-ribosyltransferase Exotoxin-S (ExoS), an early effector of the type III secretion system that is delivered into host cells to affect their transcription pattern and cytoskeletal dynamics. The purpose of this study was to formulate a real-time assay of purified recombinant ExoS activity for high throughput application. We characterized the turnover kinetics of the fluorescent dinucleotide 1,N(6)-etheno-NAD+ as co-substrate for ExoS. Further, we found that the toxin relied on any of five tested isoforms of human 14-3-3 to modify vH-Ras and the Rho-family GTPases Rac1, -2, and -3 and RhoC. We then used 14-3-3beta stimulated ExoS modification of vH-Ras to screen a collection of low-molecular weight compounds selected to target the poly-ADP ribose polymerase family and identified 3-(4-oxo-3,5,6,7-tetrahydro-4H-cyclopenta[4,5]thieno[2,3-d]pyrimidin-2 yl)propanoic acid as an ExoS inhibitor with micromolar potency. Thus, we present an optimized method to screen for inhibitors of ExoS activity that is amenable to high-throughput format and an intermediate affinity inhibitor that can serve both as assay control and as a starting point for further development. PMID- 26850639 TI - Long-term dual-color tracking of genomic loci by modified sgRNAs of the CRISPR/Cas9 system. AB - Visualization of chromosomal dynamics is important for understanding many fundamental intra-nuclear processes. Efficient and reliable live-cell multicolor labeling of chromosomal loci can realize this goal. However, the current methods are constrained mainly by insufficient labeling throughput, efficiency, flexibility as well as photostability. Here we have developed a new approach to realize dual-color chromosomal loci imaging based on a modified single-guide RNA (sgRNA) of the CRISPR/Cas9 system. The modification of sgRNA was optimized by structure-guided engineering of the original sgRNA, consisting of RNA aptamer insertions that bind fluorescent protein-tagged effectors. By labeling and tracking telomeres, centromeres and genomic loci, we demonstrate that the new approach is easy to implement and enables robust dual-color imaging of genomic elements. Importantly, our data also indicate that the fast exchange rate of RNA aptamer binding effectors makes our sgRNA-based labeling method much more tolerant to photobleaching than the Cas9-based labeling method. This is crucial for continuous, long-term tracking of chromosomal dynamics. Lastly, as our method is complementary to other live-cell genomic labeling systems, it is therefore possible to combine them into a plentiful palette for the study of native chromatin organization and genome ultrastructure dynamics in living cells. PMID- 26850640 TI - Kissing-loop interaction between 5' and 3' ends of tick-borne Langat virus genome 'bridges the gap' between mosquito- and tick-borne flaviviruses in mechanisms of viral RNA cyclization: applications for virus attenuation and vaccine development. AB - Insertion of microRNA target sequences into the flavivirus genome results in selective tissue-specific attenuation and host-range restriction of live attenuated vaccine viruses. However, previous strategies for miRNA-targeting did not incorporate a mechanism to prevent target elimination under miRNA-mediated selective pressure, restricting their use in vaccine development. To overcome this limitation, we developed a new approach for miRNA-targeting of tick-borne flavivirus (Langat virus, LGTV) in the duplicated capsid gene region (DCGR). Genetic stability of viruses with DCGR was ensured by the presence of multiple cis-acting elements within the N-terminal capsid coding region, including the stem-loop structure (5'SL6) at the 3' end of the promoter. We found that the 5'SL6 functions as a structural scaffold for the conserved hexanucleotide motif at its tip and engages in a complementary interaction with the region present in the 3' NCR to enhance viral RNA replication. The resulting kissing-loop interaction, common in tick-borne flaviviruses, supports a single pair of cyclization elements (CYC) and functions as a homolog of the second pair of CYC that is present in the majority of mosquito-borne flaviviruses. Placing miRNA targets into the DCGR results in superior attenuation of LGTV in the CNS and does not interfere with development of protective immunity in immunized mice. PMID- 26850641 TI - Knock-in of large reporter genes in human cells via CRISPR/Cas9-induced homology dependent and independent DNA repair. AB - CRISPR/Cas9-induced site-specific DNA double-strand breaks (DSBs) can be repaired by homology-directed repair (HDR) or non-homologous end joining (NHEJ) pathways. Extensive efforts have been made to knock-in exogenous DNA to a selected genomic locus in human cells; which, however, has focused on HDR-based strategies and was proven inefficient. Here, we report that NHEJ pathway mediates efficient rejoining of genome and plasmids following CRISPR/Cas9-induced DNA DSBs, and promotes high-efficiency DNA integration in various human cell types. With this homology-independent knock-in strategy, integration of a 4.6 kb promoterless ires eGFP fragment into the GAPDH locus yielded up to 20% GFP+ cells in somatic LO2 cells, and 1.70% GFP+ cells in human embryonic stem cells (ESCs). Quantitative comparison further demonstrated that the NHEJ-based knock-in is more efficient than HDR-mediated gene targeting in all human cell types examined. These data support that CRISPR/Cas9-induced NHEJ provides a valuable new path for efficient genome editing in human ESCs and somatic cells. PMID- 26850644 TI - Effects of dietary tannic acid on the growth, hepatic gene expression, and antioxidant enzyme activity in Brandt's voles (Microtus brandti). AB - This study was designed to investigate the physiological and biochemical responses of Brandt's voles to the persistent presence of dietary tannic acid. The diet for animals in the experimental group was supplemented with 3% dietary tannic acid for 5weeks. The control group received a commercial lab chow. No significant differences were detected in body weight, organ (heart, kidney, and liver) weights, and organ parameters between animals from two groups. However, voles in the experimental group had significantly higher daily food intake, increased contents of proline and histidine in saliva and feces after protein hydrolysis, and elevated hepatic expression of transferrin than the control. Our results suggested the existence of adaptive strategies developed in Brandt's voles to overcome the adverse effects of dietary tannic acid. (1) Food consumption was increased to satisfy their nutritional demands. (2) The secretion of tannic-acid-binding salivary proteins was promoted. (3) The absorption of iron was enhanced. These alterations contributed to neutralize the negative effects of tannic acid and maintain body mass in animals supplemented with tannic acid. As the result of the consumption of tannic acid, hepatic expression of 3-hydroxy-3 methylglutaryl coenzyme A reductase was significantly decreased, while the overall potential of the antioxidant system, characterized by increased hepatic enzymatic activities of catalase and glutathione peroxidase, was enhanced. Our results also implied the involvement of tannic acid in the regulation of lipid metabolism and oxidative stress in voles. PMID- 26850642 TI - Effective knockdown of Drosophila long non-coding RNAs by CRISPR interference. AB - Long non-coding RNAs (lncRNAs) have emerged as regulators of gene expression across metazoa. Interestingly, some lncRNAs function independently of their transcripts - the transcription of the lncRNA locus itself affects target genes. However, current methods of loss-of-function analysis are insufficient to address the role of lncRNA transcription from the transcript which has impeded analysis of their function. Using the minimal CRISPR interference (CRISPRi) system, we show that coexpression of the catalytically inactive Cas9 (dCas9) and guide RNAs targeting the endogenous roX locus in the Drosophila cells results in a robust and specific knockdown of roX1 and roX2 RNAs, thus eliminating the need for recruiting chromatin modifying proteins for effective gene silencing. Additionally, we find that the human and Drosophila codon optimized dCas9 genes are functional and show similar transcription repressive activity. Finally, we demonstrate that the minimal CRISPRi system suppresses roX transcription efficiently in vivo resulting in loss-of-function phenotype, thus validating the method for the first time in a multicelluar organism. Our analysis expands the genetic toolkit available for interrogating lncRNA function in situ and is adaptable for targeting multiple genes across model organisms. PMID- 26850645 TI - Concurrent validity of the international physical activity questionnaire in outpatients with bipolar disorder: Comparison with the Sensewear Armband. AB - The International Physical Activity Questionnaire (IPAQ) is a self-report questionnaire commonly used in mental health care settings to assess physical activity. However, despite its frequent use, its validity has not been investigated in people with bipolar disorder. The aim of this pilot study was to examine the concurrent validity of the energy expenditure recorded with the IPAQ compared with an objective measure, the Sensewear Armband (SWA). Twenty outpatients with bipolar disorder wore a SWA for 8 full consecutive days and subsequently completed the IPAQ. There was a significant correlation between the active (moderate and vigorous physical activity) energy expenditure as assessed with the IPAQ and SWA (minimum 10min bouts). The IPAQ overestimated active energy expenditure and underestimated total energy expenditure from physical activity by almost 40% compared with the SWA. Results demonstrate that the IPAQ should be used with caution as a measure for estimating energy expenditure from physical activity in outpatients with bipolar disorder. PMID- 26850643 TI - Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors. AB - We analyzed a multi-drug resistant (MR) HIV-1 reverse transcriptase (RT), subcloned from a patient-derived subtype CRF02_AG, harboring 45 amino acid exchanges, amongst them four thymidine analog mutations (TAMs) relevant for high level AZT (azidothymidine) resistance by AZTMP excision (M41L, D67N, T215Y, K219E) as well as four substitutions of the AZTTP discrimination pathway (A62V, V75I, F116Y and Q151M). In addition, K65R, known to antagonize AZTMP excision in HIV-1 subtype B was present. Although MR-RT harbored the most significant amino acid exchanges T215Y and Q151M of each pathway, it exclusively used AZTTP discrimination, indicating that the two mechanisms are mutually exclusive and that the Q151M pathway is obviously preferred since it confers resistance to most nucleoside inhibitors. A derivative was created, additionally harboring the TAM K70R and the reversions M151Q as well as R65K since K65R antagonizes excision. MR R65K-K70R-M151Q was competent of AZTMP excision, whereas other combinations thereof with only one or two exchanges still promoted discrimination. To tackle the multi-drug resistance problem, we tested if the MR-RTs could still be inhibited by RNase H inhibitors. All MR-RTs exhibited similar sensitivity toward RNase H inhibitors belonging to different inhibitor classes, indicating the importance of developing RNase H inhibitors further as anti-HIV drugs. PMID- 26850646 TI - Which tinnitus-related characteristics affect current health-related quality of life and depression? A cross-sectional cohort study. AB - Tinnitus is sometimes associated with lower health-related quality of life (HRQoL) and depressive symptoms. However, only limited evidence exists identifying which tinnitus characteristics are responsible for these associations. The aim of this cross-sectional study was to assess associations between tinnitus, HRQoL, depressive symptoms, subjective tinnitus loudness and audiometrically assessed tinnitus characteristics (e.g., hearing threshold). Two hundred and eight outpatients reporting tinnitus completed questionnaires on tinnitus (Tinnitus Handicap Inventory, THI), HRQoL (World-Health-Organisation Quality of Life Short Form Survey, WHOQOL-BREF), and depressive symptoms (Beck Depression Inventory, BDI), and underwent audiometry. Patients with higher THI scores exhibited significantly lower HRQoL, and higher depression scores. THI total-score, THI subscales, and subjective tinnitus loudness explained significant variance of WHOQOL-BREF and BDI. Audiometrically measured features were not associated with WHOQOL-BREF or BDI. Overall, we confirmed findings that different features of tinnitus are associated with HRQoL and depressive symptoms but not with audiometrically assessed tinnitus characteristics. Consequently, physicians should evaluate THI total score, its sub-scores, and subjective tinnitus loudness to reliably and quickly identify patients who potentially suffer from depressive symptoms or significantly lower HRQoL. Supporting these patients early might help to prevent the development of reactive depressive symptoms and impairment of HRQoL. PMID- 26850647 TI - Cognitive predictors of violent incidents in forensic psychiatric inpatients. AB - This study tested the predictive value of attentional bias, emotion recognition, automatic associations, and response inhibition, in the assessment of in-clinic violent incidents. Sixty-nine male forensic patients participated and completed an Emotional Stroop to measure attentional bias for threat and aggression, a Single Target - Implicit Association Task to assess automatic associations, a Graded Emotional Recognition Task to measure emotion recognition, and an Affective Go/NoGo to measure response inhibition. Violent incidents were derived from patient files and scored on severity level. The predictive value of level of psychopathy was tested with the Psychopathy Checklist - Revised (PCL-R). Generalized linear mixed model analyses showed that increased attention towards threat and aggression, difficulty recognizing sad faces and factor 2 of the PCL-R predicted the sum of violent incidents. Specifically, verbal aggression was predicted by increased attention towards threat and aggression, difficulty to recognize sad and happy faces, and PCL-R factor 2; physical aggression by decreased response inhibition, higher PCL-R factor 2 and lower PCL-R factor 1 scores; and aggression against property by difficulty recognizing angry faces. Findings indicate that cognitive tasks could be valuable in predicting aggression, thereby extending current knowledge on dynamic factors predicting aggressive behavior in forensic patients. PMID- 26850648 TI - [Intravenous leiomyomatosis: an unusual growth pattern in uterine myomas]. PMID- 26850649 TI - SBRT and HDR brachytherapy produce lower PSA nadirs and different PSA decay patterns than conventionally fractionated IMRT in patients with low- or intermediate-risk prostate cancer. AB - PURPOSE: To compare patterns of prostate-specific antigen (PSA) response following stereotactic body radiation therapy (SBRT), high-dose-rate (HDR) brachytherapy, and conventionally fractionated intensity modulated radiation therapy (IMRT) in patients with low- or intermediate-risk prostate cancer (CaP). METHODS AND MATERIALS: Eligible study patients included 439 patients with low- or intermediate-risk prostate cancer who were treated with radiation therapy (RT) alone between 2003 and 2013, remained free of biochemical recurrence, and had at least 2 PSA values within the first year following RT. Of these, 130 were treated with SBRT, 220 with HDR brachytherapy, and 89 with IMRT. Multivariate regression analysis was used to compare PSA nadirs (nPSA), time to nPSA, and PSA bounce parameters among the 3 modalities. Indicator variable analysis was used to develop empirical models of PSA decay using the treatment modalities as indicator variables. RESULTS: Significantly more patients treated with SBRT or HDR brachytherapy achieved raw nPSAs of <0.5 ng/mL compared with patients treated with IMRT (76.2% and 75.9% vs 44.9%, respectively; P < .0001 for SBRT or HDR brachytherapy vs IMRT). On multivariate analysis, nPSA was significantly lower with SBRT and HDR compared with IMRT (P < .0001). Time to nPSA and bounce parameters was not significantly different among IMRT, SBRT, and HDR. Overall, SBRT and HDR brachytherapy caused significantly larger PSA decay rates (P < .001). When truncating follow-up at 1000 days, the corresponding decay rates were larger for all 3 modalities, with no significant differences between them. CONCLUSIONS: Stereotactic body radiation therapy and HDR brachytherapy produce lower nPSAs than IMRT. Within 1000 days of follow-up, the modalities produce similar rates of PSA decay; subsequently, decay continues (albeit at a slower pace) after SBRT and HDR brachytherapy but plateaus with IMRT. Because nPSA is a validated predictor of long-term outcome, these data not only suggest a distinct radiobiological effect with SBRT and HDR brachytherapy, but also predict for clinical outcomes that might equal or surpass those of IMRT. PMID- 26850650 TI - Steroid and anticonvulsant prophylaxis for stereotactic radiosurgery: Large variation in physician recommendations. AB - PURPOSE/OBJECTIVE(S): The risk of developing symptomatic edema or seizure following stereotactic radiosurgery (SRS) is poorly defined, and many practitioners prescribe prophylactic corticosteroids and/or anticonvulsants. Because there are no clear guidelines regarding appropriate use, we sought to characterize prescribing practices and factors associated with these recommendations. METHODS AND MATERIALS: We conducted a 1-time, internet-based survey among 500 randomly selected radiation oncologists self-described as specializing in central nervous system diseases who were registered in the American Society for Radiation Oncology directory. Physicians were contacted by e mail and invited to complete the 22-question survey. RESULTS: The response rate was 32% (n = 161). Sixty-six percent of respondents had been in practice for >10 years, and 45% of respondents practiced at an academic medical center. During/after SRS, 53% of respondents "always" or "usually" recommended corticosteroids, whereas 47% "never," "rarely," or "sometimes" recommended them. When prescribing corticosteroids, the recommended duration of use was <1 week, 1 2 weeks, or >2 weeks among 49%, 33%, and 18% of respondents, respectively. Respondents who worked in an academic medical center were less likely to prescribe corticosteroids, although this did not reach significance (P = .09). Seizure prophylaxis was less common overall, as 79% of respondents "rarely" or "never" prescribed anticonvulsants for SRS. Respondents who prescribed anticonvulsants more frequently had higher estimations of the risk of seizure within 2 weeks of SRS (P < .001), and their recommended duration of anticonvulsant use was <1 week, 1-2 weeks, and >2 weeks among 35%, 25%, and 41% of respondents, respectively. CONCLUSIONS: There is extreme variation in physician recommendations regarding prophylactic corticosteroid and anticonvulsant use for patients undergoing SRS. Further investigation of the risks and benefits of these medications for SRS is warranted, which may promote guideline development and more patient-centered, rational prescribing practices. PMID- 26850651 TI - The implementation and assessment of a quality and safety culture education program in a large radiation oncology department. AB - In 2010, the American Society for Radiation Oncology launched a national campaign to improve patient safety in radiation therapy. One recommendation included the expansion of educational programs dedicated to quality and safety. We subsequently implemented a quality and safety culture education program (Q-SCEP) in our large radiation oncology department. The purpose of this study is to describe the design, implementation, and impact of this Q-SCEP. METHODS AND MATERIALS: In 2010, we instituted a comprehensive Q-SCEP, consisting of a longitudinal series of lectures, meetings, and interactive workshops. Participation was mandatory for all department members across all network locations. Electronic surveys were administered to assess employee engagement, knowledge retention, preferred learning styles, and the program's overall impact. The Agency for Healthcare Research and Quality (AHRQ) Survey on Patient Safety Culture was administered. Analysis of variance was used for statistical analysis. RESULTS: Between 2010 and 2015, 100% of targeted staff participated in Q-SCEP. Thirty-three percent (132 of 400) and 30% (136 of 450) responded to surveys in 2012 and 2014, respectively. Mean scores improved from 73% to 89% (P < .001), with the largest improvement seen among therapists (+21.7%). The majority strongly agreed that safety culture education was critical to performing their jobs well. CONCLUSIONS: Full course compliance was achieved despite the sizable number of personnel and treatment centers. Periodic assessments demonstrated high knowledge retention, which significantly improved over time in nearly all department divisions. Additionally, our AHRQ patient safety grade remains high and continues to improve. These results will be used to further enhance ongoing internal safety initiatives and to inform future innovative efforts. PMID- 26850652 TI - Obstructive sleep apnoea syndrome is an under-recognized cause of uncontrolled asthma across the life cycle. PMID- 26850653 TI - Limitations of evidence-based medicine. PMID- 26850654 TI - Evaluation and management of the patient with multiple syringomas: A systematic review of the literature. AB - Syringomas are benign adnexal tumors with distinct histopathologic features, including the characteristic comma ("tadpole") shaped tail comprised of dilated, cystic eccrine ducts. Clinically, syringomas typically present in adolescent females predominantly in the periorbital region. They may present as solitary or multiple lesions, and more rare sites of involvement include the genitals, palms, scalp, and the chest. Over the past 50 years, there have been >800 reported cases of syringoma either alone or in conjunction with a systemic syndrome, most commonly Down syndrome. The primary aim of this systematic review is to discuss the clinical features and associations of syringomas with a focus on the patient with multiple syringomas. Its secondary aims are to explore pathophysiology with a focus on multiple syringomas and provide comprehensive data on both traditional and novel treatments. Importantly, multiple syringomas present across a broad clinical spectrum. Though noted in many textbooks to be related to tumor syndromes, the association of syringomas with inherited tumor syndromes is only rarely reported in the literature. Despite multiple reported cases of syringoma, the pathophysiology remains poorly understood and treatment continues to pose a significant challenge. PMID- 26850655 TI - The effect of increasing the dose of hydroxychloroquine (HCQ) in patients with refractory cutaneous lupus erythematosus (CLE): An open-label prospective pilot study. AB - BACKGROUND: Up to 30% of patients with cutaneous lupus erythematosus (CLE) fail to respond to hydroxychloroquine (HCQ). OBJECTIVES: We sought to evaluate the efficacy of increased daily doses of HCQ on cutaneous response in refractory CLE. METHODS: We conducted an open-label prospective study between 2010 and 2014. Patients with CLE and HCQ blood level less than or equal to 750 ng/mL were included. The daily dose of HCQ was increased to reach blood concentrations greater than 750 ng/mL. The primary end point was the number of responders defined by an improvement of CLE Disease Area and Severity Index score (4 points or 20% decrease) in patients with HCQ blood concentration greater than 750 ng/mL. RESULTS: We included 34 patients (26 women; median age 45 [range 28-72] years). Two nonadherent patients were excluded. The median CLE Disease Area and Severity Index score before treatment was significantly improved after treatment (8 [range 2-30] vs 1.5 [range 0-30]), P < .001). The primary response criterion was reached in 26 (81%) of the 32 patients analyzed. A decrease in HCQ doses without further CLE flare (median follow-up 15.8 [range 3.06-77.4] months) was achieved in 15 of the 26 responders. LIMITATIONS: The main limitations of the study are its open label design and the limited number of patients included. CONCLUSIONS: Increasing HCQ doses to reach blood concentrations greater than 750 ng/mL should be considered before addition of other treatments in refractory CLE. PMID- 26850656 TI - Skin infections among US high school athletes: A national survey. AB - BACKGROUND: Skin infections have long been a reported problem among high school athletes, particularly wrestlers. There has yet to be a national study describing the epidemiology of skin infections across multiple high school sports. OBJECTIVE: We sought to report the epidemiology of skin infections among US high school athletes. METHODS: High school sports-related skin infections resulting in time loss were reported by a convenience sample of US high schools from 2009/2010 through 2013/2014 via High School Reporting Information Online. RESULTS: During the study, 474 skin infections were reported among 20,858,781 athlete exposures, a rate of 2.27 per 100,000 athlete exposures. The largest number of skin infections occurred in wrestling (73.6%) followed by football (17.9%). The most common infections were bacterial (60.6%) and tinea (28.4%) infections. Body parts most often affected were the head/face (25.3%) followed by the forearm (12.7%). LIMITATIONS: The study included only high schools with National Athletic Trainers' Association-affiliated athletic trainers, which may limit generalizability. However, using athletic trainers as data reporters improved data quality. CONCLUSIONS: Skin infections are an important subset of high school sports-related adverse events. An understanding of the epidemiology of sports related skin infections should promote awareness and drive evidence-based prevention efforts. PMID- 26850659 TI - How to select the frontline treatment for a patient with peripheral T-cell lymphoma. AB - Peripheral T-cell lymphomas are a diverse group of lymphoproliferative disorders with differing clinical presentations and biological behavior. The optimal treatment of these diseases is determined by an accurate diagnosis as well as determination of the unique phenotype, genetics and prognostic factors of each disease entity. While combination chemotherapy is the backbone of treatment for these patients, many patients may benefit from additional therapy such as brentuximab vedotin, radiation therapy, or stem cell transplantation. PMID- 26850658 TI - Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression. AB - Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-1 on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-1 infection and that ILC numbers did not recover after resolution of peak viremia. ILC numbers were preserved by antiretroviral therapy (ART), but only if initiated during acute infection. Transcriptional profiling during the acute phase revealed upregulation of genes associated with cell death, temporally linked with a strong IFN acute-phase response and evidence of gut barrier breakdown. We found no evidence of tissue redistribution in chronic disease and remaining circulating ILCs were activated but not apoptotic. These data provide a potential mechanistic link between acute HIV-1 infection, lymphoid tissue breakdown, and persistent immune dysfunction. PMID- 26850657 TI - MicroRNAs 24 and 27 Suppress Allergic Inflammation and Target a Network of Regulators of T Helper 2 Cell-Associated Cytokine Production. AB - MicroRNAs (miRNAs) are important regulators of cell fate decisions in immune responses. They act by coordinate repression of multiple target genes, a property that we exploited to uncover regulatory networks that govern T helper-2 (Th2) cells. A functional screen of individual miRNAs in primary T cells uncovered multiple miRNAs that inhibited Th2 cell differentiation. Among these were miR-24 and miR-27, miRNAs coexpressed from two genomic clusters, which each functioned independently to limit interleukin-4 (IL-4) production. Mice lacking both clusters in T cells displayed increased Th2 cell responses and tissue pathology in a mouse model of asthma. Gene expression and pathway analyses placed miR-27 upstream of genes known to regulate Th2 cells. They also identified targets not previously associated with Th2 cell biology which regulated IL-4 production in unbiased functional testing. Thus, elucidating the biological function and target repertoire of miR-24 and miR-27 reveals regulators of Th2 cell biology. PMID- 26850661 TI - In silico prediction of the G-protein coupled receptors expressed during the metamorphic molt of Sagmariasus verreauxi (Crustacea: Decapoda) by mining transcriptomic data: RNA-seq to repertoire. AB - Against a backdrop of food insecurity, the farming of decapod crustaceans is a rapidly expanding and globally significant source of food protein. Sagmariasus verreauxi spiny lobster, the subject of this study, are decapods of underdeveloped aquaculture potential. Crustacean neuropeptide G-protein coupled receptors (GPCRs) mediate endocrine pathways that are integral to animal fecundity, growth and survival. The potential use of novel biotechnologies to enhance GPCR-mediated physiology may assist in improving the health and productivity of farmed decapod populations. This study catalogues the GPCRs expressed in the early developmental stages, as well as adult tissues, with a view to illuminating key neuropeptide receptors. De novo assembled contiguous sequences generated from transcriptomic reads of metamorphic and post metamorphic S. verreauxi were filtered for seven transmembrane domains, and used as a reference for iterative re-mapping. Subsequent putative GPCR open reading frames (ORFs) were BLAST annotated, categorised, and compared to published orthologues based on phylogenetic analysis. A total of 85 GPCRs were digitally predicted, that represented each of the four arthropod subfamilies. They generally displayed low-level and non-differential metamorphic expression with few exceptions that we examined using RT-PCR and qPCR. Two putative CHH-like neuropeptide receptors were annotated. Three dimensional structural modelling suggests that these receptors exhibit a conserved extracellular ligand binding pocket, providing support to the notion that these receptors co-evolved with their ligands across Decapoda. This perhaps narrows the search for means to increase productivity of farmed decapod populations. PMID- 26850662 TI - [Consideration and discussion on ten hot issues of endocrine therapy for breast cancer]. AB - Endocrine therapy is one of the main treatment for hormone receptor positive breast cancer. In recent years, some of the critical results of clinical studies have been published, triggering a heat discussion. Guidelines and expert consensus have made appropriate updates based on some results. However, the selection and duration of the endocrine therapy for premenopausal women, the judgment of the menstrual conditions, the application of ovarian function suppression and the choice of endocrine drug combining with ovarian function suppress, and monitoring the endometrial thickness and hormone levels during therapy, as well as the endocrine therapy for postmenopausal patients and metastatic cancer are still controversial. Based on the evidence from study and clinical experience, this article will focus and discuss the ten hot issues. PMID- 26850663 TI - [Neoadjuvant treatment in human epidermal growth factor receptor 2-positive breast cancer]. AB - Breast cancer is the most prevalent malignancy among females worldwide. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer represents a subtype with aggressive behavior, poor response to treatment and unfavorable prognosis. Anti-HER2-based neoadjuvant treatment has improved clinical outcomes of patients with HER2-positive disease. Pathological complete response (pCR) after neoadjuvant treatment indicates a favorable prognosis. With the development of HER2-targeted therapy and neoadjuvant treatment, numerous studies focus on the predictive factors of pCR or therapeutic resistance of anti-HER2 therapy. Identification of novel predictive factors in HER2-positive breast cancer, such as tumor-infiltrating lymphocytes, will be helpful for clinical decision. PMID- 26850664 TI - [Disparities of breast cancer burden between China and western countries and its implication]. AB - The disease burden of breast cancer in China is growing, and its proportion contributed to the global burden is increasing accordingly. The western countries have achieved reduction of mortality and slow growth of incidence, while the breast cancer incidence and mortality rates have been increasing constantly with lower survival rates in China. The remarkable characteristics of breast cancer burden in China is the disparities of the current status and time trends of incidence, mortality and survival between urban and rural area. The breast cancer disease distributions and time trends in China and the differential from the developed countries are described, which may be benefit to draw the international experience on prevention, early detection, medical care and survival management. Assessment of the existing evidence, elaboration of the prevention, control strategies in consideration of Chinese social-economic and culture situation would be beneficial to rise to the future challenge. PMID- 26850660 TI - Jun-Mediated Changes in Cell Adhesion Contribute to Mouse Embryonic Stem Cell Exit from Ground State Pluripotency. AB - Embryonic stem cells (ESC) are able to give rise to any somatic cell type. A lot is known about how ESC pluripotency is maintained, but comparatively less is known about how differentiation is promoted. Cell fate decisions are regulated by interactions between signaling and transcriptional networks. Recent studies have shown that the overexpression or downregulation of the transcription factor Jun can affect the ESC fate. Here we have focussed on the role of the Jun in the exit of mouse ESCs from ground state pluripotency and the onset of early differentiation. Transcriptomic analysis of differentiating ESCs reveals that Jun is required to upregulate a programme of genes associated with cell adhesion as ESCs exit the pluripotent ground state. Several of these Jun-regulated genes are shown to be required for efficient adhesion. Importantly this adhesion is required for the timely regulated exit of ESCs from ground state pluripotency and the onset of early differentiation events. Stem Cells 2016;34:1213-1224. PMID- 26850665 TI - [Long-term survival analysis of different breast cancer molecular subtypes: Shanghai Breast Cancer Survival Study]. AB - OBJECTIVES: To analyze the survival of breast cancer molecular subtypes and to examine the effect of therapy on the long-term prognosis of different subtypes. METHODS: This study included 3 586 breast cancer patients with estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2) information in Shanghai Breast Cancer Survival Study, a population-based prospective cohort study established in 2002. Molecular subtypes, based on immunohistochemistry were categorized as follows: Luminal A, Luminal B, HER2, and triple-negative subtype. Characteristics and clinical data were collected through questionnaires and medical records at baseline survey and sequential follow-up surveys. Survival rates of different molecular subtypes were analyzed and compared with Log-rank tests. Multiple Cox regression models were used to evaluate the effect of therapy on long-term prognosis of different molecular subtypes. RESULTS: Among the 3 586 cases, Luminal A, Luminal B, HER2 and triple negative breast cancer subtypes accounted for 54.5%, 16.6%, 13.9%, and 14.9%, respectively. With a median follow-up of 10.3 years (ranging 0.6 to 12.8 years), the 10-year overall survival (OS) rates for the four subtypes were 82.7% (95% CI: 80.9% to 84.4%), 77.7% (95% CI: 74.1% to 80.8%), 76.3% (95% CI: 72.3% to 79.8%), and 74.8% (95% CI: 70.9% to 78.3%), respectively. The 10-year disease to free survival (DFS) rates were 79.0% (95% CI: 76.7% to 81.0%), 76.0% (95% CI: 71.9% to 79.5%), 73.6% (95% CI: 68.9% to 77.7%), and 74.5% (95% CI: 69.4% to 78.9%), respectively. Significant difference in survival among four subtypes was observed (Log-rank test, P<0.01). Multivariate Cox regression indicated that hormonal therapy can significantly reduce the long-term risk of total mortality and recurrence breast cancer specific mortality among Luminal A subtype patients. Adjuvant chemotherapy could improve the long-term prognosis of triple-negative breast cancer. No benefit from radiotherapy was observed for four subtypes of breast cancer in terms of long-term prognosis. CONCLUSIONS: Molecular subtypes based on ER/PR/HER2 could provide important information to predict breast cancer prognosis. The hormonal status was an important basis for individualized therapy and precision medicine. PMID- 26850666 TI - [Analysis on clinical and pathological characteristics of 66 patients with stage IV breast cancer]. AB - OBJECTIVES: To explore the clinical and pathological characteristics of stage IV breast cancer and to analyze their relationship with the morbidity and prognosis. METHODS: The records of 66 patients presenting from January 2008 to December 2014 with stage IV breast cancer were reviewed. All of the patients were women and the median age was 57.5 (31 to 80) years, accounted for 3.01% (66/2 189) among the breast cancer patients treated in the same period. Statistical methods were used to analyze the correlation between clinical and pathological characteristics such as T-stage, N-stage, immuno-histo-chemistry and the morbidity and prognosis of stage IV breast cancer. The influence of patients characteristics to metastasis were compared by chi(2) test. Kaplan-Meier curves were reported for overall survival (OS), and the Log-rank test was used to compare the difference in groups. Cox proportional models were fitted for multivariate analysis. RESULTS: The median survival time of stage IV breast cancer was 56.0 months and the 5-year survival rate was 40%. To metastasis, the effects of age, subtypes, histological grade, hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)had no significant statistics differences. It was concluded that the expression of HER2 (P=0.003) and HR (P=0.001) as well as single metastasis (P=0.029) were the influencing factors of the survival by multivariate Cox regression analysis. Primary tumor R0 surgery group and no surgery group had no significant statistics differences of overall survival and the 5-year survival rate (P=0.102). CONCLUSIONS: Clinical and pathological characteristics have no effect on metastasis. The expression of HER2 and HR as well as single metastasis play important roles in survival. PMID- 26850667 TI - [Risk factors of non-sentinel lymph node metastasis and performance of MSKCC nomogramin breast cancer patients with metastatic sentinel lymph node]. AB - OBJECTIVES: To study the factors influencing the non-sentinel lymph node(NSLN) status and to assess performance of Memorial Sloan-Kettering Cancer Center (MSKCC) nomogram in predicting sentinel lymph node(SLN) metastases in a SLN positive Chinese breast cancer population. METHODS: Data were collected from breast cancer patients who were diagnosed with pathological positive sentinel lymph node and received further axillary lymph node dissection(ALND) in Shanghai Ruijin Hospital from January 2011 to August 2014. MSKCC nomogram was used to calculate each patient's NSLN metastasis risk score. The receiver operator characteristic curve (ROC curve) and the area under the ROC curve (AUC) was used to assess the predictive accuracy of the model. RESULTS: Among the 1 147 patients who received sentinel biopsy, 150 SLN positive patients who received ALND were enrolled in this study. By univariate analysis, multifocal breast cancer (chi(2)=5.887, P=0.015), SLN+ /SLN ratio (chi(2)=6.683, P=0.010) and abnormal axillary lymph node displayed by ultrasound (chi(2)=7.736, P=0.005) were the influencing factors of NSLN metastases. By multivariate analysis, multifocal breast cancer (OR=7.25, 95% CI: 1.73 to 30.43, P=0.007), SLN+ /SLN ratio >= 0.5 (OR=2.564, 95% CI: 1.22 to 5.39, P=0.013) and abnormal axillary lymph node displayed by ultrasound (OR=2.471, 95% CI: 1.18 to 5.19, P=0.017) were the independent influencing factors of NSLN metastases. The AUC of MSKCC nomogram in this population was 0.677. CONCLUSIONS: For breast cancer patients with positive sentinel lymph node, multifocality, SLN+ /SLN ratio and axillary lymphadenopathy displayed by ultrasound is related to NSLN metastasis. MSKCC has low accuracy in predicting NSLN status of this population. PMID- 26850668 TI - [Safety of breast-conserving treatment for triple-negative breast cancer]. AB - OBJECTIVE: To investigate the effect of risk factors on ipsilateral breast tumor recurrence (IBTR) and distant disease-free survival (DDFS) for patients with triple-negative breast cancer (TNBC) who underwent breast-conserving treatment (BCT). METHODS: A series of 1 835 patients with primary breast cancer treated with BCT in a single institute between December 1999 and August 2010 were analyzed retrospectively. Totally 1 614 patients, whose characteristics were intact, were analyzed to compare their outcomes with respect to the incidence of IBTR, DDFS and disease-free survival (DFS). All of patients were female. Median age was 47 years (ranging 21 to 92 years, interquartile range 14 years). According to the immunohistochemical results of the patients, 1 614 cases were divided into TNBC group (n=308) and non-TNBC group (n=1 306). The risk factors of relapse after breast-conserving treatment (age at diagnosis, spread to axillary lymph nodes, hormone receptor status, neoadjuvant chemotherapy, and maximal tumor diameter, human epidermal growth factor receptor 2 (HER-2) status, preoperative MRI, the location and extent of the tumor bed defined by CT scans for electron boost planning as part of breast radiotherapy) were studied.chi(2) test was used to compare the distribution of baseline characteristics among subtypes. The probability of survival (or relapse occurrence), and DDFS were calculated using the Kaplan-Meier method. Cumulative incidence functions were used to describe the cumulative hazard from LR, IBTR and DDFS in the presence of competing risks. RESULTS: A total of 1 614 women with primary breast cancer underwent a breast conserving surgery followed by radiotherapy. The median follow-up period was 77 months (interquartile range 36 months). One hundred and forty patients (8.6%) were lost to follow-up. Overall 5-year IBTR rate was 3.1% (95% CI: 2.2% to 4.0%), 5-year DDFS rate was 95.8% (95% CI: 94.9% to 96.7%) and 5-year DFS rate was 93.8% (95% CI: 92.7% to 94.9%). Lymph nodal involvement (HR=3.03, 95% CI: 1.66 to 5.51, P=0.000) and use of CT information in boost field planning (HR=0.40, 95% CI: 0.20 to 0.80, P=0.010) were associated significantly with IBTR in Cox multivariable analysis. Multivariable analysis showed that TNBC doesn't have a significantly increased risk of IBTR compared with the non-TNBC subtype (HR=0.90, 95% CI: 0.50 to 1.76, P=0.78). TNBC was not an independent risk factor for DDFS or DFS. The multivariable model showed significant effect of nodal status and age at diagnosis on 5-year DDFS rate and 5-year DFS rate. CONCLUSIONS: Breast-conserving treatment for TNBC is not associated with increased IBTR compared with non-TNBC subtype. Use of CT information in boost field planning can reduce the risk of ipsilateral breast tumor recurrence for patients undergoing BCT. PMID- 26850670 TI - [Effect of Cdc42 gene inhibited on proliferation, migration and invasion in human hepatocellular carcinoma cells]. AB - OBJECTIVE: To investigate the effect of Cdc42-shRNA plasmid to proliferation, migration, invasion and other malignant biological behavior in hepatoma SMMC-7721 cells. METHODS: Cdc42-shRNA interfering vector transfected to SMMC-7721 cells with liposome method. The growth curve of transfected cells SMMC-7721, U6 control, Cdc42-shRNA2 was detected by MTT. The cells mobility was detected by wound healing experiment. Transwell chamber experiments to observe the cell migration and invasion. Detected AFP and PCNA expression level by Western blot.Human hepatoma SMMC-7721 transplanted subcutaneously in nude mouse, detected the expression of Cdc42 of the tumor by immunohistochemistry.t test was used to analyze the data between two groups. RESULTS: The doubling time of Cdc42-shRNA2, U6-control and SMMC7721 was 42.7 h, 34.9 h and 35.1 h. The relative migration distance of Cdc42-shRNA2 and U6-control on 36 h was (47.1 +/- 4.1)% and (86.6 +/- 5.3)% (t=-10.21, P<0.05). Transwell chamber experimental methods showed the numbers of permeating cells were 18.2 +/- 2.1(Cdc42-shRNA2) and 41.0 +/- 3.5 (U6 control) (t=-9.67, P<0.05) on 24 h. The AFP and PCNA expression of hepatoma cells is significantly inhibited after the Cdc42-shRNA2 was transfected compared with U6-control group.The tumor average weight of group Cdc42-shRNA2 was (335.1 +/- 178.2) mg, which was much lighter than that of SMMC-7721 group ((925.3 +/- 241.4) mg) and U6-control group ((910.5 +/- 225.6) mg) (t=-4.47, -4.39; P<0.05) and the Cdc42 expression was also weak positive. CONCLUSION: Cdc42 interfere with plasmid significant changes in human malignant biological behavior of hepatocellular carcinoma cells, and reduces liver cancer cell growth, invasion and metastasis of capacity. PMID- 26850671 TI - [Advances in studies on metabolic syndrome and breast cancer]. AB - Breast cancer is one of the most common malignancies in women. Over these years, the morbidity of metabolic syndrome (MS) has also been increasing in China, probably due to changes in economies and lifestyles. As a result, the association to between these two diseases has at tracted much attention. Results demonstrated the presence of MS was associated with breast cancer risk, and the risk became higher when more MS components were present compared to no components. Moreover, a specific association was indicated between MS and breast cancer recurrence and metastasis to some extent as well. Further, for breast cancer patients, being diagnosed with MS can increase the mortality and lead to poor prognosis. The mechanisms underlying the association is not clear yet, but several factors are speculated to be the possible causes, including the elevated level of insulin, insulin like growth factor-1, leptin and pro-inflammatory cytokines, the decreased level of adiponectin as well as the interaction between DBC1 and SIRT1. The prognosis of patients with breast cancer combined MS can be improved by means of changing diet habits, increasing physical activities and drug-intervention. Although the specific mechanisms underlying the association are still need to be elucidated, better understanding of the association must help us with new strategies for the prevention and treatment of breast cancer. PMID- 26850669 TI - [Diagnosis and treatment of primary intraspinal melanocytoma]. AB - OBJECTIVE: To investigate the clinical features, diagnostic and therapeutic strategy of primary intraspinal melanocytoma. METHOD: The clinical data of primary intraspinal melanocytoma patients who underwent surgical operations from June 2011 to December 2014 in Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University were retrospectively reviewed. RESULTS: Six cases of intraspinal melanocytoma, identified with pathology were collected, including 5 male and 1 female patients with the average age of 39.8 years (range 23-50 years). Limbs anesthesia and weakness were present in 2 cases. Neck and back pain were present in 4 cases. All patients performed MRI examination before operation, and only 1 case was diagnosed as primary melanocytoma, and the others were confirmed by postoperative pathology. All cases were confirmed by the pathological examination. Total resection was achieved in 2 cases, subtotal resection was achieved in 2 cases, 2 disseminated cases only achieved partial resection. The average period of postoperative follow-up process was 25.7 months(range 9-52 months). One case recurred in 9 months after surgery and died in 16 months, one case recurred in 1 year after surgery, and the other 4 cases had no recurrence. The recurrenced 2 patients had been not treated with radiotherapy, 2 patients of the 4 that not recurrenced had received radiotherapy. All patients didn't receive chemotherapy. The other patients were in good condition after surgery. CONCLUSIONS: The intraspinal primary melanocytoma is less likely to recurrence and metastasis if total resection is achieved. Diagnosis relies on pathology. Surgery is the first choice and early total resection is strongly recommend. Appropriate radiotherapy for partial resection cases can delay tumor recurrence. PMID- 26850672 TI - [Influence of oversizing of endovascular stent-graft to prognosis of aortic dissection]. AB - With the increasing application of endovascular stent-graft in the treatment of aortic dissection, there are still some problems and controversies in the selection of the stent-graft oversizing. This review summarized the latest research in the study of the baseline and measurement in stent-graft oversizing selection, the relationship between stent-graft oversizing and prognosis and the selection of stent-graft oversizing in different patients with different conditions, providing a reference for the endovascular stent-graft oversizing selection in the treatment of aortic dissection. PMID- 26850673 TI - [Research progress of peripheral applications of drug-eluting stent]. AB - In-stent restenosis severely reduces the long-term patency rate after stent implantation, but drug-eluting stent may be possible to solve this problem. This paper mainly from two aspects of the mechanism of in-stent restenosis and clinical trials to state progress in research of drug-eluting stent in the applications of peripheral artery disease. PMID- 26850674 TI - The "Strengthening Nursing Culture Project" - an exploratory evaluation study of nursing students' placements within Aboriginal Medical Services. AB - BACKGROUND: Cultural awareness and cultural competence have been the focus of the transcultural nursing literature that has explored the roles and responsibilities of nurses in their care of Aboriginal and Torres Strait Islander Peoples. Cultural immersion programs, upholding cultural safety and cultural humility, offer valuable guidance to the education of nursing students regarding Aboriginal and Torres Strait Islander health and cultures. OBJECTIVES: This study seeks to explore nursing students' experiences of a cultural immersion program within Aboriginal Medical Services (AMSs) in New South Wales, Australia. DESIGN: Eight nursing students participated in a mixed methods design exploratory study of their clinical placement within AMSs. METHODS: A survey gathered data regarding levels of preparation and confidence, learning barriers, placement stressors and personal reflections. FINDINGS: Nursing students reported positive and transformative experiences of intercultural learning. CONCLUSIONS: Cultural immersion programs provide a valuable framework for the design and evaluation of clinical placement programs for nursing students within intercultural learning spaces. PMID- 26850676 TI - Pharmacokinetic properties and bioequivalence of orally inhaled salbutamol in healthy Chinese volunteers. AB - CONTEXT: Salbutamol is a short-acting beta2-adrenergic receptor agonist that has been used for many years for relief of bronchospasm. However, studies on the pharmacokinetic profile of orally inhaled salbutamol doses used in clinical practice have not yet been reported in Chinese subjects. OBJECTIVE: The aim of this study was to compare the pharmacokinetics and evaluate the bioequivalence of two orally inhaled salbutamol formulations. MATERIALS AND METHODS: A single-dose randomized fasting two-period, two-treatment and two-sequence crossover open label bioequivalence study was conducted in 24 healthy Chinese adult male volunteers, with a 1-week washout period between treatments. Plasma concentrations of salbutamol were determined using liquid chromatography coupled to tandem mass spectrometry. Pharmacokinetic parameters, including AUC0-0.33 h, AUC0-24 h and Cmax were calculated and the 90% confidence intervals of the ratio (test/reference) pharmacokinetic parameters were obtained by analysis of variance on logarithmically transformed data. RESULTS: The mean (SD) pharmacokinetic parameters of the reference drug were AUC0-0.33 h, 227.2 (89.9) pg.h/ml; AUC0-24 h, 2551.9 (1008.0) pg.h/ml; Cmax, 801.3 (307.3) pg/ml and t1/2, 5.14(1.36) h. Those of the test drug were AUC0-0.33 h, 244.0 (104.4) pg.h/ml; AUC0-24 h, 2664.4 (1081.8) pg.h/ml; Cmax, 873.7 (374.4) pg/ml, t1/2, 5.29 (1.23) h. The median value for Tmax was 0.25 h for both formulations. The 90% confidence intervals for the AUC0-0.33 h, AUC0-24 h and Cmax were in the range of 0.892-1.208, 0.876-1.195 and 0.911-1.203, respectively. CONCLUSION: This single-dose study found that the test and reference products met the regulatory criteria for bioequivalence of China in healthy Chinese volunteers. PMID- 26850675 TI - Early afterdepolarizations promote transmural reentry in ischemic human ventricles with reduced repolarization reserve. AB - AIMS: Acute ischemia is a major cause of sudden arrhythmic death, further promoted by potassium current blockers. Macro-reentry around the ischemic region and early afterdepolarizations (EADs) caused by electrotonic current have been suggested as potential mechanisms in animal and isolated cell studies. However, ventricular and human-specific arrhythmia mechanisms and their modulation by repolarization reserve remain unclear. The goal of this paper is to unravel multiscale mechanisms underlying the modulation of arrhythmic risk by potassium current (IKr) block in human ventricles with acute regional ischemia. METHODS AND RESULTS: A human ventricular biophysically-detailed model, with acute regional ischemia is constructed by integrating experimental knowledge on the electrophysiological ionic alterations caused by coronary occlusion. Arrhythmic risk is evaluated by determining the vulnerable window (VW) for reentry following ectopy at the ischemic border zone. Macro-reentry around the ischemic region is the main reentrant mechanism in the ischemic human ventricle with increased repolarization reserve due to the ATP-sensitive potassium current (IK(ATP)) activation. Prolongation of refractoriness by 4% caused by 30% IKr reduction counteracts the establishment of macro-reentry and reduces the VW for reentry (by 23.5%). However, a further decrease in repolarization reserve (50% IKr reduction) is less anti-arrhythmic despite further prolongation of refractoriness. This is due to the establishment of transmural reentry enabled by electrotonically triggered EADs in the ischemic border zone. EADs are produced by L-type calcium current (ICaL) reactivation due to prolonged low amplitude electrotonic current injected during the repolarization phase. CONCLUSIONS: Electrotonically-triggered EADs are identified as a potential mechanism facilitating intramural reentry in a regionally-ischemic human ventricles model with reduced repolarization reserve. PMID- 26850677 TI - Biochar and compost amendments enhance copper immobilisation and support plant growth in contaminated soils. AB - Contamination of soil with trace elements, such as Cu, is an important risk management issue. A pot experiment was conducted to determine the effects of three biochars and compost on plant growth and the immobilisation of Cu in a contaminated soil from a site formerly used for wood preservation. To assess Cu mobility, amended soils were analysed using leaching tests pre- and post incubation, and post-growth. Amended and unamended soils were planted with sunflower, and the resulting plant material was assessed for yield and Cu concentration. All amendments significantly reduced leachable Cu compared to the unamended soil, however, the greatest reductions in leachable Cu were associated with the higher biochar application rate. The greatest improvements in plant yields were obtained with the higher application rate of biochar in combination with compost. The results suggest joint biochar and compost amendment reduces Cu mobility and can support biomass production on Cu-contaminated soils. PMID- 26850678 TI - Preclinical and first-in-human phase I studies of KW-2450, an oral tyrosine kinase inhibitor with insulin-like growth factor receptor-1/insulin receptor selectivity. AB - Numerous solid tumors overexpress or have excessively activated insulin-like growth factor receptor-1 (IGF-1R). We summarize preclinical studies and the first in-human study of KW-2450, an oral tyrosine kinase inhibitor with IGF-1R and insulin receptor (IR) inhibitory activity. Preclinical activity of KW-2450 was evaluated in various in vitro and in vivo models. It was then evaluated in a phase I clinical trial in 13 patients with advanced solid tumors (NCT00921336). In vitro, KW-2450 inhibited human IGF-1R and IR kinases (IC50 7.39 and 5.64 nmol/L, respectively) and the growth of various human malignant cell lines. KW 2450 40 mg/kg showed modest growth inhibitory activity and inhibited IGF-1 induced signal transduction in the murine HT-29/GFP colon carcinoma xenograft model. The maximum tolerated dose of KW-2450 was 37.5 mg once daily continuously; dose-limiting toxicity occurred in two of six patients at 50 mg/day (both grade 3 hyperglycemia) and in one of seven patients at 37.5 mg/day (grade 3 rash). Four of 10 evaluable patients showed stable disease. Single-agent KW-2450 was associated with modest antitumor activity in heavily pretreated patients with solid tumors and is being further investigated in combination therapy with lapatinib/letrozole in patients with human epidermal growth factor receptor 2 postive metastatic breast cancer. PMID- 26850679 TI - An Approach to Improve the Negative Predictive Value and Clinical Utility of Transthoracic Echocardiography in Suspected Native Valve Infective Endocarditis. AB - BACKGROUND: In patients with suspected native valve infective endocarditis, current guidelines recommend initial transthoracic echocardiography (TTE) followed by transesophageal echocardiography (TEE) if clinical suspicion remains. The guidelines do not account for the quality of initial TTE or other findings that may alter the study's diagnostic characteristics. This may lead to unnecessary TEE when initial TTE was sufficient to rule out vegetation. METHODS: The objective of this study was to determine if the use of a strict definition of negative results on TTE would improve the performance characteristics of TTE sufficiently to exclude vegetation. A retrospective analysis of patients at a single institution with suspected native valve endocarditis who underwent TTE followed by TEE within 7 days between January 1, 2007, and February 28, 2014, was performed. Negative results on TTE for vegetation were defined by either the standard approach (no evidence of vegetation seen on TTE) or by applying a set of strict negative criteria incorporating other findings on TTE. Using TEE as the gold standard for the presence of vegetation, the diagnostic performance of the two transthoracic approaches was compared. RESULTS: In total, 790 pairs of TTE and TEE were identified. With the standard approach, 661 of the transthoracic studies had negative findings (no vegetation seen), compared with 104 studies with negative findings using the strict negative approach (meeting all strict negative criteria). The sensitivity and negative predictive value of TTE for detecting vegetation were substantially improved using the strict negative approach (sensitivity, 98% [95% CI, 95%-99%] vs 43% [95% CI, 36%-51%]; negative predictive value, 97% [95% CI, 92%-99%] vs 87% [95% CI, 84%-89%]). CONCLUSIONS: The ability of TTE to exclude vegetation in patients is excellent when strict criteria for negative results are applied. In patients at low to intermediate risk with strict negative results on TTE, follow-up TEE may be unnecessary. PMID- 26850680 TI - New Reference Centiles for Left Ventricular Mass Relative to Lean Body Mass in Children. AB - BACKGROUND: Echocardiographic measurement of left ventricular (LV) mass is routinely performed in pediatric patients with elevated cardiovascular risk. The complex relationship between heart growth and body growth in children requires normalization of LV mass to determine its appropriateness relative to body size. LV mass is strongly determined by lean body mass (LBM). Using new LBM predictive equations, the investigators generated sex-specific LV mass-for-LBM centile curves for children 5 to 18 years of age. METHODS: This retrospective study used M-mode echocardiographic data collected from 1995 through 2003 from 939 boys and 771 girls between 5 and 18 years of age (body mass index < 85th percentile for sex and age) to create smoothed sex-specific LV mass-for-LBM reference centile curves using the Lamda Mu Sigma method. The newly developed reference centiles were applied to children with essential hypertension and with chronic kidney disease, groups known to be at high risk for LV hypertrophy (LVH). The identification of LVH using two different normalization approaches was compared: LV mass-for-LBM and LV mass index-for-age percentiles. RESULTS: Among 231 children at risk for LVH, on average, relative LV mass was higher using the LV mass index-for-age percentile method than the LV mass-for-LBM percentile method. LVH was more likely to be diagnosed among overweight children and less likely among thin children. CONCLUSIONS: This study provides new LV mass reference centiles expressing LV mass relative to LBM, the strongest determinant of LV mass. These reference centiles may allow more accurate stratification of cardiovascular risk in children. PMID- 26850681 TI - Sex-by-formulation interaction assessed through a bioequivalence study of efavirenz tablets. AB - Although sex-related differences in gastrointestinal physiology have been vastly reported, its impact on drug oral bioavailability and bioequivalence (product discrimination) is often ignored. On this work results from an average bioequivalence study between tablets containing 600mg of the antiretroviral efavirenz (EFV), carried out with 14 healthy subjects (8 female and 6 men) in a randomized 2-period, 2-treatment crossover design, are analyzed from a sex-based approach. Sequences were balanced within each sex group. Considering all subjects, no differences were observed on EFV absorbed amount, as shown by the estimated 90CI of the AUC96 Test/Reference bioequivalence ratio (T/R): 0.950 1.05. However, results were not conclusive due to the 90CI for CMAX T/R was 0.743 1.07. Over this parameter, a significant sex-by-formulation interaction was detected: 90CI CMAX T/R was 0.838-1.36 in women and 0.540-0.920 in men; with a 52% relative difference between point estimates. Formulation differences were therefore evidenced only by male subjects. In vitro dissolution and disintegration tests for both products were carried out in two aqueous media: A) SLS 0.25% and B) HCl/KCl pH1.2. T/R results for dissolution efficiency and tablet disintegration times of formulations in both A and B media were highly correlated with CMAX T/R bioequivalence results observed in women and men respectively, showing that a dissimilar gastrointestinal environment between sexes affected EFV oral absorption. This work shows how sex-by-formulation interaction can affect bioequivalence conclusions. Sex effect on product discrimination should be specially disclosed in bioequivalence studies, mainly for drugs aimed to be given to both sexes. PMID- 26850682 TI - Investigation of a suitable in vitro dissolution test for itraconazole-based solid dispersions. AB - The difficulty to find a relevant in vitro dissolution test to evaluate poorly soluble drugs is a well-known issue. One way to enhance their aqueous solubility is to formulate them as amorphous solid dispersions. In this study, three formulations containing itraconazole (ITZ), a model drug, were tested in seven different conditions (different USP apparatuses and different media). Two of the formulations were amorphous solid dispersions namely Sporanox(r), the marketed product, and extrudates composed of Soluplus(r) and ITZ produced by hot melt extrusion; and the last one was pure crystalline ITZ capsules. After each test, a ranking of the formulations was established. Surprisingly, the two amorphous solid dispersions exhibited very different behavior depending primarily on the dissolution media. Indeed, the extrudates showed a better release profile than Sporanox(r) in non-sink and in biphasic conditions, whilst Sporanox(r) showed a higher release profile than the extrudates in sink and fasted simulated gastric conditions. The disintegration, dynamic light scattering and nuclear magnetic resonance results highlighted the presence of interaction between the surfactants and Soluplus(r), which slowed down the erosion of the polymer matrix. Indeed, the negative charge of sodium dodecyl sulfate (SDS) and bile salts interacted with the surface of the extrudates that formed a barrier through which the water hardly diffused. Moreover, Soluplus(r) and SDS formed mixed micelles in solution in which ITZ interacts with SDS, but no longer with Soluplus(r). Regarding the biphasic dissolution test, the interactions between the octanol dissolved in the aqueous media disrupted the polymer--ITZ system leading to a reduced release of ITZ from Sporanox(r), whilst it had no influence on the extrudates. All together these results pointed out the difficulty of finding a suitable in vitro dissolution test due to interactions between the excipients that complicates the prediction of the behavior of these solid dispersions in vivo. PMID- 26850683 TI - Interrater reliability of the cervicothoracic and shoulder physical examination in patients with a primary complaint of shoulder pain. AB - OBJECTIVE: Examine the interrater reliability of cervicothoracic and shoulder physical examination in patients with a primary complaint of shoulder pain. DESIGN: Single-group repeated-measures design for interrater reliability. SETTING: Orthopaedic physical therapy clinics. PARTICIPANTS: Twenty-one patients with a primary complaint of shoulder pain underwent a standardized examination by a physical therapist (PT). A PT conducted the first examination and one of two additional PTs conducted the 2nd examination. MAIN OUTCOME MEASURES: The Cohen kappa and weighted kappa were used to calculate the interrater reliability of ordinal level data. Intraclass correlation coefficients model 2,1 (ICC2,1) and the 95% confidence intervals were calculated to determine the interrater reliability. RESULTS: The kappa coefficients ranged from -.24 to .83 for the mobility assessment of the glenohumeral, acromioclavicular and sternoclavicular joints. The kappa coefficients ranged from -.20 to .58 for joint mobility assessment of the cervical and thoracic spine. The kappa coefficients ranged from .23 to 1.0 for special tests of the shoulder and cervical spine. CONCLUSIONS: The present study reported the reliability of a comprehensive upper quarter physical examination for a group of patients with a primary report of shoulder pain. The reliability varied considerably for the cervical and shoulder examination and was significantly higher for the examination of muscle length and cervical range of motion. PMID- 26850684 TI - A subchronic feeding study of dicamba-tolerant soybean with the dmo gene in Sprague-Dawley rats. AB - The dicamba-tolerant soybean MON87708 expresses the dicamba mono-oxygenase (DMO) enzyme that is encoded by the dmo gene. In order to evaluate the safety of this soybean, a 90-day subchronic feeding toxicity study (13 weeks) was conducted on Sprague-Dawley rats. A total of 140 rats were divided into 7 groups (10/sex/group), including a standard commercial diet control group. The genetically modified (GM) soybean MON87708 and the near isogenic non-GM soybean A3525 were respectively processed to unhulled, full-fat, and heat-treated powder, then mixed into the diet at levels of 7.5%, 15%, and 30% (wt/wt) with the main nutrients of the various diets balanced and then fed to 6 groups. The remaining group of rats fed with a commercial rat diet served as blank control. Some isolated parameters indicated statistically significant differences in body weight, feed consumption/utilization, hematology, serum biochemistry, and relative organ weights. These differences were not consistent across gender or test-diet dose, which were attributed to incidental and biological variability. In conclusion, the results demonstrated that the transgenic soybean MON87708 containing DMO was as safe as non-transgenic isogenic counterpart with historical safe use. PMID- 26850685 TI - Derivation of a No-significant-risk-level (NSRL) for dermal exposures to diethanolamine. AB - Diethanolamine (DEA) has been found to produce liver and kidney tumors in mice following lifetime dermal exposures. Data regarding the mode of action by which DEA produces these tumors were used to support a dose-response assessment that resulted in a no-significant-risk-level (NSRL) for dermal exposures to DEA. DEA and its metabolites are structural analogs to endogenous agents important to choline homeostasis. Sufficient information is available to support an epigenetic MOA involving the perturbation of choline homeostasis and hepatic methylation reactions in the formation of mouse liver tumors. This MOA may also apply to mouse kidney tumors, but direct measurements for key events in kidney are lacking. For both tumor types, dose-response data were pooled across four cancer bioassays conducted for DEA and DEA-containing condensates in order to provide a more robust characterization of the dose-response relationships. Doses were expressed in terms of dermally absorbed dose so that the dose-dependency and species differences in the dermal absorption of DEA were addressed. The resulting NSRL value of 3400 ug/day for dermal exposures to DEA is considered to be protective of human health for both tumor endpoints. PMID- 26850686 TI - Intestinal Microbiota in Inflammatory Bowel Disease and Carcinogenesis: Implication for Therapeutics. AB - Trillions of bacteria inhabit our intestine, forming a community called the microbiota, whose contributions are essential to maintain host homeostasis. Disruption of this normal microbial-host communication network has deleterious consequences for the host and is associated with intestinal pathologies such as inflammatory bowel diseases (IBD) and colorectal cancer (CRC). Here we present key concepts and mechanisms by which bacteria may participate in intestinal pathology, and discuss possible means to therapeutically target the microbiome. PMID- 26850687 TI - Early-diverging wood-decaying fungi detected using three complementary sampling methods. AB - Wood-decaying fungi are essential components of degradation systems in forest ecosystems. However, their species diversity and ecological features are largely unknown. Three methods are commonly used to investigate fungal diversity: fruiting body collection, culturing, and environmental DNA analysis. Because no single method fully characterises fungal diversity, complementary approaches using two or more methods are required. However, few studies have compared the different methods and determined the best way to characterise fungal diversity. To this end, we investigated wood-decomposing Dacrymycetes (Agaricomycotina, Basidiomycota) using a complementary approach combining fruiting body collection, culturing, and environmental DNA analysis, thereby offering an effective approach for investigating the diversity of saprotrophic mushrooms. Fruiting body collection, culturing, and environmental DNA analysis detected 11, 10, and 16 operational taxonomic units (OTUs; 25 OTUs in total) and identified three, seven, and seven novel lineages, respectively. The three methods were complementary to each other to detect greater Dacrymycetes diversity. The culturing and environmental DNA analysis identified three early-diverging lineages that were not identified in the fruiting body collection suggesting that diverse lineages lacking observable fruiting bodies remain undiscovered. Such lineages may be important to understand Dacrymycetes evolution. To detect early branches of Dacrymycetes more efficiently, we recommend a combined approach consisting of a primary environmental DNA survey to detect novel lineages and a secondary culture survey to isolate their living mycelia. This approach would be helpful for identifying otherwise-undetectable lineages, and could thus uncover missing links that are important for understanding the evolution of mushroom-forming fungi. PMID- 26850688 TI - Evaluation of Interference of Cellular Phones on Electronic Apex Locators: An In Vitro Study. AB - INTRODUCTION: Use of mobile phone has been prohibited in many hospitals to prevent interference with medical devices. Electromagnetic radiation emitted from cellular phones might interfere with electronic working length determination. The purpose of this in vitro study was to evaluate the effect of a smart phone (Samsung Galaxy Note Edge) on working length determination of electronic apex locators (EALs) Propex II and Rootor. METHODS: Fifteen intact, non-carious single rooted teeth were decoronated at the cementoenamel junction. Visually, working length was determined by using a #15 K-file under stereomicroscope (*20). The effect of cellular phones on electronic working length (EWL) was determined under 2 experimental settings: (1) in a closed room with poor signal strength and (2) in a polyclinic set up with good signal strength and 5 conditions: (1) electronically, without cellular phone in room; (2) electronically, with cellular phone in physical contact with EAL; (3) electronically, with mobile phone in physical contact with EAL and in calling mode for a period of 25 seconds; (4) electronically, mobile phone placed at a distance of 40 cm from the EAL; and (5) electronically, mobile phone placed at a distance of 40 cm and in calling mode for a period of 25 seconds. The EWL was measured 3 times per tooth under each condition. Stability of the readings was scored from 1 to 3: (1) good stability, (2) stable reading after 1 attempt, and (3) stable reading after 2 attempts. The data were compared by using analysis of variance. RESULTS: The EWL measurements were not influenced by the presence of cellular phone and could be determined under all experimental conditions. CONCLUSIONS: Within the limitations of this study, it can be concluded that mobile phones do not interfere with the EWL determination. PMID- 26850689 TI - Rhodiola crenulata induces an early estrogenic response and reduces proliferation and tumorsphere formation over time in MCF7 breast cancer cells. AB - BACKGROUND: Rhodiola crenulata is a Tibetan mountainous plant, commonly used in Eastern alternative medicine. Many phytochemicals possess estrogenic activity, a critical regulator of proliferation in mammary epithelial cells. We have previously characterized anti-cancer properties of R. crenulata in aggressive triple negative breast cancer cells, lacking the expression of estrogen receptor. Currently, it is unknown whether R. crenulata exerts estrogenic effects and as such consumption may be a concern for women with estrogen receptor positive breast cancer that use Rhodiola sp. to relieve mild to moderate depression. PURPOSE: In this study, we wished to determine whether a hydroalcoholic fraction of the R. crenulata root extract exhibits estrogenic activity in estrogen receptor positive (ER+) breast cancer cells in vitro and whether it affects normal mammary epithelial ER target gene expression in vivo. METHODS: ER transcriptional activity was analyzed in MCF7 cells expressing an ERE reporter construct and confirmed via qPCR of endogenous ER target genes. We also monitored cellular proliferation over time. Additionally, to assess stem-like properties in MCF7 cells, we performed a tumorsphere formation assay under anchorage independent conditions. We examined whether R. crenulata treatment reduced beta catenin levels via Western blotting and measured beta-catenin transcriptional activity by a reporter assay. To examine the effects of R. crenulata on normal mammary epithelial cells, we performed immunohistochemical staining of ER and PR in the mammary glands of mice fed R. crenulata for 12 weeks. RESULTS: We show an initial activation of ER transcriptional activity by dual reporter assay, qPCR and proliferation of MCF7 ER+ cells in response to 24 h of R. crenulata treatment. However, upon longer treatment basal and R. crenulata induced transcriptional activity was suppressed. There was a decrease in cell doubling times and a decrease in tumorsphere formation. In association with these changes, ERalpha transcript levels were decreased and active beta-catenin levels were reduced in the cells treated for 2 weeks. Finally, we show no change in estrogen targets in normal mammary cells in vivo. CONCLUSION: These data suggest that the R. crenulata extract contains components with estrogenic activity. However, R. crenulata treatment could still be protective in ER+ breast cancer cells, as longer treatment reduced the transcriptional activity of beta-catenin and ER responses leading to reduced proliferation and tumorsphere formation. Furthermore, administration of 20 mg/kg/day R. crenulata to mice did not have an observable effect on mammary epithelial ERalpha target gene expression in vivo. PMID- 26850690 TI - The Crohn's Disease-Ulcerative Colitis Clinical Appraisal. PMID- 26850691 TI - Y-chromosome identification in circulating cell-free fetal DNA using surface plasmon resonance. AB - OBJECTIVE: Since the discovery of cell-free fetal DNA (cffDNA) in maternal plasma, diagnostic non-invasive prenatal methods have been developed or optimized for fetal sex determination and identification of genetic diseases. As far as fetal sex determination, this might be important for therapeutic intervention on sex-associated pathologies such as Duchenne muscular dystrophy, hemophilia and congenital adrenal hyperplasia. Surface plasmon resonance (SPR)-based biosensors might be useful for these studies, because they allow to monitor the molecular interactions in real-time providing qualitative and quantitative information, through kinetics, affinity and concentration analyses. METHODS: The BiacoreTM X100 has been applied to identify Y-chromosome sequence in cffDNA obtained from plasma samples of 26 pregnant women at different gestational ages. We have performed SPR-based analysis of SRY PCR products using SRY-specific probes immobilized on the sensor chip. RESULTS: We have demonstrated that there is a statistically significant difference between samples collected by pregnancies carrying male or female fetuses. Moreover, cffDNA obtained at early gestational ages and not detectable by conventional quantitative real-time PCR can be discriminated with high accuracy and reliability using SPR-based biosensors. CONCLUSIONS: These data, in addition to their direct applicability in more extensive diagnostic trials, should be considered as the basis of future developments. PMID- 26850692 TI - Iron overload enhances human mesenchymal stromal cell growth and hampers matrix calcification. AB - BACKGROUND: Iron overload syndromes include a wide range of diseases frequently associated with increased morbidity and mortality. Several organs are affected in patients with iron overload including liver, heart, joints, endocrine glands, and pancreas. Moreover, severe bone and hemopoietic tissue alterations are observed. Because of the role of bone marrow mesenchymal stromal cells (BM-MSCs) in bone turnover and hematopoiesis, iron effects on primary BM-MSCs cultures were evaluated. METHODS: Primary human BM-MSCs cultures were prepared and the effects of iron on their proliferation and differentiation were characterized by biochemical analyses and functional approaches. RESULTS: Addition of iron to the culture medium strongly increased BM-MSCs proliferation and induced their accelerated S phase entry. Iron enters BM-MSCs through both transferrin-dependent and transferrin-independent mechanisms, inducing the accumulation of cyclins E and A, the decrease of p27(Kip1), and the activation of MAPK pathway. Conversely, neither apoptotic signs nor up-regulation of reactive oxygen species were observed. Iron inhibited both differentiation of BM-MSCs into osteoblasts and in vitro matrix calcification. These effects result from the merging of inhibitory activities on BM-MSCs osteoblastic commitment and on the ordered matrix calcification process. CONCLUSIONS: We demonstrated that BM-MSCs are a target of iron overload. Iron accelerates BM-MSCs proliferation and affects BM-MSCs osteoblastic commitment, hampering matrix calcification. GENERAL SIGNIFICANCE: Our study reports, for the first time, that iron, at concentration found in overloaded patient sera, stimulates the growth of BM-MSCs, the BM multipotent stromal cell component. Moreover, iron modulates the physiological differentiation of these cells, affecting bone turnover and remodeling. PMID- 26850693 TI - Betaine chemistry, roles, and potential use in liver disease. AB - BACKGROUND: Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver its primary role is in metabolism as a methyl group donor. In both organs, a specific betaine transporter mediates cellular uptake of betaine from plasma. The abundance of both betaine and the betaine transporter in liver greatly exceeds that of other organs. SCOPE OF REVIEW: The remarkable contributions of betaine to normal human and animal health are summarized together with a discussion of the mechanisms and potential beneficial effects of dietary betaine supplements on liver disease. MAJOR CONCLUSIONS: A significant amount of data from animal models of liver disease indicates that administration of betaine can halt and even reverse progression of the disruption of liver function. Betaine is well-tolerated, inexpensive, effective over a wide range of doses, and is already used in livestock feeding practices. GENERAL SIGNIFICANCE: The accumulated data indicate that carefully controlled additional investigations in humans are merited. The focus should be on the long-term use of betaine in large patient populations with liver diseases characterized by development of fatty liver, especially non-alcoholic fatty liver disease and alcoholic liver disease. PMID- 26850694 TI - GSTZ1 expression and chloride concentrations modulate sensitivity of cancer cells to dichloroacetate. AB - Dichloroacetate (DCA), commonly used to treat metabolic disorders, is under investigation as an anti-cancer therapy due to its ability to reverse the Warburg effect and induce apoptosis in tumor cells. While DCA's mechanism of action is well-studied, other factors that influence its potential as a cancer treatment have not been thoroughly investigated. Here we show that expression of glutathione transferase zeta 1 (GSTZ1), the enzyme responsible for conversion of DCA to its inactive metabolite, glyoxylate, is downregulated in liver cancer and upregulated in some breast cancers, leading to abnormal expression of the protein. The cellular concentration of chloride, an ion that influences the stability of GSTZ1 in the presence of DCA, was also found to be abnormal in tumors, with consistently higher concentrations in hepatocellular carcinoma than in surrounding non-tumor tissue. Finally, results from experiments employing two- and three-dimensional cultures of HepG2 cells, parental and transduced to express GSTZ1, demonstrate that high levels of GSTZ1 expression confers resistance to the effect of high concentrations of DCA on cell viability. These results may have important clinical implications in determining intratumoral metabolism of DCA and, consequently, appropriate oral dosing. PMID- 26850695 TI - Subtle alterations of excitatory transmission are linked to presynaptic changes in the hippocampus of PINK1-deficient mice. AB - Homozygous or heterozygous mutations in the PTEN-induced kinase 1 (PINK1) gene have been linked to early-onset Parkinson's disease (PD). Several neurophysiological studies have demonstrated alterations in striatal synaptic plasticity along with impaired dopamine release in PINK1-deficient mice. Using electrophysiological methods, here we show that PINK1 loss of function causes a progressive increase of spontaneous glutamate-mediated synaptic events in the hippocampus, without influencing long-term potentiation. Moreover, fluorescence analysis reveals increased neurotrasmitter release although our biochemical results failed to detect which presynaptic proteins might be engaged. This study provides a novel role for PINK1 beyond the physiology of nigrostriatal dopaminergic circuit. Specifically, PINK1 might contribute to preserve synaptic function and glutamatergic homeostasis in the hippocampus, a brain region underlying cognition. The subtle changes in excitatory transmission here observed might be a pathogenic precursor to excitotoxic neurodegeneration and cognitive decline often observed in PD. Using electrophysiological and fluorescence techniques, we demonstrate that lack of PINK1 causes increased excitatory transmission and neurotransmitter release in the hippocampus, which might lead to the cognitive decline often observed in Parkinson's disease. PMID- 26850697 TI - The future of biology in driving the field of hyperthermia. AB - In 2011 Hanahan and Weinberg updated their well-established paper 'The hallmarks of cancer'. The rationale for that review and its predecessor was to produce a conceptual framework for future research in cancer. The original Hallmarks included: cell signalling to enhance tumour cell proliferation, acquisition of ability to evade growth suppressors, developing mechanisms to resist cell death, enabling replicative immortality, initiating angiogenesis and activating processes to enable invasion and metastasis. In the more recent paper, Hanahan and Weinberg added important new features to this composite paradigm. The new features were: (1) altered metabolism, (2) evasion of immune destruction, (3) tumour promoting inflammation, and (4) the cellular microenvironment. These four new features are the main focus of this review. Hanahan and Weinberg did not specifically include the physiological microenvironment which is dominated by hypoxia and acidosis. In this review we will consider these features in addition to the cellular and metabolic components of the microenvironment. The purpose of this review is to present a vision of emerging fields of study in hyperthermia biology over the next decade and beyond. As such, we are focusing our attention on pre-clinical studies, primarily using mice. The application of hyperthermia in human patients has been thoroughly reviewed elsewhere. PMID- 26850696 TI - Population genomics of the filarial nematode parasite Wuchereria bancrofti from mosquitoes. AB - Wuchereria bancrofti is a parasitic nematode and the primary cause of lymphatic filariasis--a disease specific to humans. W. bancrofti currently infects over 90 million people throughout the tropics and has been acknowledged by the world health organization as a vulnerable parasite. Current research has focused primarily on the clinical manifestations of disease and little is known about the evolutionary history of W. bancrofti. To improve upon knowledge of the evolutionary history of W. bancrofti, we whole genome sequenced 13 W. bancrofti larvae. We circumvent many of the difficulties of multiple infections by sampling larvae directly from mosquitoes that were experimentally inoculated with infected blood. To begin, we used whole genome data to reconstruct the historical population size. Our results support a history of fluctuating population sizes that can be correlated with human migration and fluctuating mosquito abundances. Next, we reconstructed the putative pedigree of W. bancrofti worms within an infection using the kinship coefficient. We deduced that there are full-sib and half-sib relationships residing within the same larval cohort. Through combined analysis of the mitochondrial and nuclear genomes we concluded that this is likely a results of polyandrous mating, the first time reported for W. bancrofti. Lastly, we scanned the genomes for signatures of natural selection. Annotation of putative selected regions identified proteins that may have aided in a parasitic life style or may have evolved to protect against current drug treatments. We discuss our results in the greater context of understanding the biology of an animal with a unique life history and ecology. PMID- 26850698 TI - Human urinary exosome proteome unveils its aerobic respiratory ability. AB - Exosomes are 40-100-nm vesicles released by most cell types after fusion of multivesicular endosomes with the plasma membrane. Exosomes, ubiquitary in body fluids including urines, contain proteins and RNA species specific of the tissue of origin. Exosomes from urine have been extensively studied as a promising reservoir for disease biomarkers. Here, we report the proteome analysis of urinary exosomes compared to urinoma, studied by Orbitrap mass spectrometry. A discovery approach was utilized on the sample. 3429 proteins were present, with minimal overlapping among exosome and urinoma. 959 proteins (28%) in exosome and 1478 proteins (43%) in urinoma were exclusively present in only one group. By cytoscape analysis, the biological process gene ontology was correlated to their probability (P <= 0.05) to be functional. This was never studied before and showed a significant clustering around metabolic functions, in particular to aerobic ATP production. Urinary exosomes carry out oxidative phosphorylation, being able to synthesize ATP and consume oxygen. A previously unsuspected function emerges for human urinary exosomes as bioactive vesicles that consume oxygen to aerobically synthesize ATP. Determination of normal human urine proteome can help generate the healthy urinary protein database for comparison, useful for various renal diseases. BIOLOGICAL SIGNIFICANCE: The findings reported represent a significant advance in the understanding of the healthy human urinary proteome. The methodology utilized to analyze the collection of proteomic data allowed the assessment of the unique composition of urinary exosomes with respect to urinoma and to elucidate the presence in the former of molecular pathways previously unknown. The paper has the potential to impact its field of research, due to the biological relevance of the metabolic capacity of urinary exosomes, which may represent their important general feature. PMID- 26850699 TI - Secretome protein signature of human pancreatic cancer stem-like cells. AB - Emerging research has demonstrated that pancreatic ductal adenocarcinoma (PDAC) contains a sub-population of cancer stem cells (CSCs) characterized by self renewal, anchorage-independent-growth, long-term proliferation and chemoresistance. The secretome analysis of pancreatic CSCs has not yet been performed, although it may provide insight into tumour/microenvironment interactions and intracellular processes, as well as to identify potential biomarkers. To characterize the secreted proteins of pancreatic CSCs, we performed an iTRAQ-based proteomic analysis to compare the secretomes of Panc1 cancer stem-like cells (Panc1 CSCs) and parental cell line. A total of 72 proteins were found up-/down-regulated in the conditioned medium of Panc1 CSCs. The pathway analysis revealed modulation of vital physiological pathways including glycolysis, gluconeogenesis and pentose phosphate. Through ELISA immunoassays we analysed the presence of the three proteins most highly secreted by Panc1 CSCs (ceruloplasmin, galectin-3, and MARCKS) in sera of PDAC patient. ROC curve analysis suggests ceruloplasmin as promising marker for patients negative for CA19-9. Overall, our study provides a systemic secretome analysis of pancreatic CSCs revealing a number of secreted proteins which participate in pathological conditions including cancer differentiation, invasion and metastasis. They may serve as a valuable pool of proteins from which biomarkers and therapeutic targets can be identified. BIOLOGICAL SIGNIFICANCE: The secretome of CSCs is a rich reservoir of biomarkers of cancer progression and molecular therapeutic targets, and thus is a topic of great interest for cancer research. The secretome analysis of pancreatic CSCs has not yet been performed. Recently, our group has demonstrated that Panc-1 CSCs isolated from parental cell line by using the CSC selective medium, represent a model of great importance to deepen the understanding of the biology of pancreatic adenocarcinoma. To our knowledge, this is the first proteomic study of pancreatic CSC secretome. We performed an iTRAQ-based analysis to compare the secretomes of Panc1 CSCs and Panc1 parental cell line and identified a total of 43 proteins secreted at higher level by pancreatic cancer stem cells. We found modulation of different vital physiological pathways (such as glycolysis and gluconeogenesis, pentose phosphate pathway) and the involvement of CSC secreted proteins (for example 72kDa type IV collagenase, galectin-3, alpha-actinin-4, and MARCKS) in pathological conditions including cancer differentiation, invasion and metastasis. By ELISA verification we found that MARCKS and ceruloplasmin discriminate between controls and PDAC patients; in addition ROC curve analyses indicate that MARCKS does not have diagnostic accuracy, while ceruloplasmin could be a promising marker only for patients negative for CA19-9. We think that the findings reported in our manuscript advance the understanding of the pathways implicated in tumourigenesis, metastasis and chemoresistance of pancreatic cancer, and also identify a pool of proteins from which novel candidate diagnostic and therapeutic biomarkers could be discovered. PMID- 26850700 TI - Efficient Synthesis and Biological Evaluation of a Novel Series of 1,5 Benzodiazepine Derivatives as Potential Antimicrobial Agents. AB - A series of novel 1,5-benzodiazepine derivatives were rationally designed and synthesized following the principle of the superposition of bioactive substructures by the combination of 1,5-benzodiazepine, pyridine (phenyl), and an ester group. The structures of the target compounds were determined by (1) H NMR, (13) C NMR, MS, IR, and elemental analysis. All the synthesized compounds were evaluated for their antimicrobial activities in vitro against the fungi C. neoformans, C. neoformans clinical isolates (ATCC 32264), C. albicans (ATCC 10231), Gram-negative bacterium E. coli (ATCC 44752), and Gram-positive bacterium S. aureus (ATCC 25923). The results of the bioactive assay demonstrated that most of the tested compounds exhibited variable inhibitory effects on the growth of the tested microorganisms. All the active compounds showed better antifungal activity than antibacterial activity. Notably, compound 2b displayed the highest activity (MIC = 30 MUg/mL) against C. neoformans and (MIC = 31 MUg/mL) against C. neoformans clinical isolates. In addition, compound 2a also showed excellent activity against C. neoformans and C. neoformans clinical isolates with minimum inhibitory concentration of 35 and 36 MUg/mL, respectively. Compounds 2a and 2b were further studied by evaluating their cytotoxicities, and the results showed that they have relatively low level cytotoxicity for BV2 and 293T cell. Preliminary structure-activity relationship study on three diverse sets (C-2, C 3, and C-8 positions) of 1,5-benzodiazepines was performed. The results revealed that the presence of a -CH3 group at the C-8 position had a positive effect on the inhibitory activity of these compounds. Additionally, the 2-pyridyl group at the C-2 position may be a pharmacophore and -COOC2 H5 at C-3 position is the best substituent for the maintenance of antimicrobial activities. PMID- 26850702 TI - Are residents of aged care facilities willing to have their medications deprescribed? AB - PURPOSE: There has been recent interest in deprescribing, particularly among older people. No previous studies have assessed whether residents of aged care facilities are willing to have their medications deprescribed. Understanding residents' attitudes toward deprescribing is important for developing deprescribing interventions. OBJECTIVE: To investigate residents' willingness to have their medications deprescribed. METHODS: This was a cross-sectional survey of 232 residents aged >=65 years from six residential aged care facilities (RACFs) across metropolitan and regional South Australia. Overall, 163 of the 232 residents (70.3%) took >=9 regular medications. All participants completed the 10 item Patients' Attitudes Towards Deprescribing (PATD) questionnaire. RESULTS: Overall, 40.5% of residents reported a desire to stop taking one or more of their medications. If their doctor said it was possible, 78.9% of residents were willing to have one or more of their medications deprescribed. Residents taking >=9 medications were more likely to feel that they were taking a large number of medications compared to residents taking <9 medications (50.3% vs 14.5%, P < 0.01), and were more likely to believe one or more of their medications was causing side effects (14.7% vs 10.1%, P = 0.02). However, residents taking >=9 regular medications were not significantly more likely to want to reduce their number of medications than residents taking <9 medications. CONCLUSIONS: Deprescribing interventions are likely to be acceptable to residents' of RACFs, with a high willingness to discontinue medicines if doctors say it is possible. This highlights the importance of the proactive involvement of health care professionals in an individualized deprescribing process. PMID- 26850703 TI - Modeling bond correlations in denatured proteins and polypeptides. AB - Bond-orientational correlations for finite-length homopolypeptides and a selected group of denatured proteins are obtained by numerical simulations using a polypeptide model with a potential of mean force. These correlations characterize the stiffness of the polypeptide backbone and are generally described by either an exponential or a power-law decay in the asymptotic limit. However, for finite length polypeptides and unfolded proteins the correlations significantly deviate from either single exponential or power-law behavior. A heuristic model is developed to analyze the correlations of homopolypeptides, which depends on the chain length and the side-chain properties. The model contains power-law and multi-exponential terms, the latter which could be interpreted as local persistence lengths. In the asymptotic limit, the model reduces to the expected power-law behavior. Simulations of denatured proteins show that the power-law behavior of the correlations is significantly suppressed and only the multi exponential term is needed to model the correlations. In addition, average persistence lengths (ranging from 2.0 to 2.5 nm) are obtained from the correlations by fitting single exponentials and shown to be in general agreement with experiments, which also assume single exponential decay. (c) 2016 Wiley Periodicals, Inc. Biopolymers 105: 312-323, 2016. PMID- 26850701 TI - Individual sympathetic postganglionic neurons coinnervate myenteric ganglia and smooth muscle layers in the gastrointestinal tract of the rat. AB - A full description of the terminal architecture of sympathetic axons innervating the gastrointestinal (GI) tract has not been available. To label sympathetic fibers projecting to the gut muscle wall, dextran biotin was injected into the celiac and superior mesenteric ganglia (CSMG) of rats. Nine days postinjection, animals were euthanized and stomachs and small intestines were processed as whole mounts (submucosa and mucosa removed) to examine CSMG efferent terminals. Myenteric neurons were counterstained with Cuprolinic Blue; catecholaminergic axons were stained immunohistochemically for tyrosine hydroxylase. Essentially all dextran-labeled axons (135 of 136 sampled) were tyrosine hydroxylase positive. Complete postganglionic arbors (n = 154) in the muscle wall were digitized and analyzed morphometrically. Individual sympathetic axons formed complex arbors of varicose neurites within myenteric ganglia/primary plexus and, concomitantly, long rectilinear arrays of neurites within circular muscle/secondary plexus or longitudinal muscle/tertiary plexus. Very few CSMG neurons projected exclusively (i.e., ~100% of an arbor's varicose branches) to myenteric plexus (~2%) or smooth muscle (~14%). With less stringent inclusion criteria (i.e., >=85% of an axon's varicose branches), larger minorities of neurons projected predominantly to either myenteric plexus (~13%) or smooth muscle (~27%). The majority (i.e., ~60%) of all individual CSMG postganglionics formed mixed, heterotypic arbors that coinnervated extensively (>15% of their varicose branches per target) both myenteric ganglia and smooth muscle. The fact that ~87% of all sympathetics projected either extensively or even predominantly to smooth muscle, while simultaneously contacting myenteric plexus, is consistent with the view that these neurons control GI muscle directly, if not exclusively. J. Comp. Neurol. 524:2577-2603, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26850704 TI - First case of hepatopancreatic necrosis disease in pond-reared Chinese mitten crab, Eriocheir sinensis, associated with microsporidian. AB - An epidemic of hepatopancreatic necrosis disease (HPND) with a high mortality rate (40%-50%) recently occurred in the cultured Chinese mitten crab, Eriocheir sinensis, which is a very important economic crustacean species in China. Histology revealed infection by a microsporidian parasite within the cytoplasm of the epithelial cells of the hepatopancreas. Numerous discrete inclusions in the infected cells and presumably free parasite spores were also observed. By negative staining using electron microscopy, a typical morphology of spores was observed with a protuberant front of the anchoring disc. Infection was confined to the epithelial cells of the hepatopancreas, with no other organ implicated. By sequencing the PCR products using specific primers based on conserved regions of microsporidian small subunit (18S) ribosomal DNA, it was revealed that the parasite from HPND ponds had 99% sequence identity to that of Hepatospora eriocheir. Phylogentic analysis also placed the microsporidian in the same lineage as H. eriocheir. This study reported the first case of widespread infections of H. eriocheir associated with HPND found in the pond-reared Chinese mitten crab, E. sinensis. The description of microsporidian in this important commercial host is fundamental for future consideration of factors affecting stock health and sustainability. PMID- 26850705 TI - Cell Transplantation and Neuroengineering Approach for Spinal Cord Injury Treatment: A Summary of Current Laboratory Findings and Review of Literature. AB - Spinal cord injury (SCI) can cause severe traumatic injury to the central nervous system (CNS). Current therapeutic effects achieved for SCI in clinical medicine show that there is still a long way to go to reach the desired goal of full or significant functional recovery. In basic medical research, however, cell transplantation, gene therapy, application of cytokines, and biomaterial scaffolds have been widely used and investigated as treatments for SCI. All of these strategies when used separately would help rebuild, to some extent, the neural circuits in the lesion area of the spinal cord. In light of this, it is generally accepted that a combined treatment may be a more effective strategy. This review focuses primarily on our recent series of work on transplantation of Schwann cells and adult stem cells, and transplantation of stem cell-derived neural network scaffolds with functional synapses. Arising from this, an artificial neural network (an exogenous neuronal relay) has been designed and fabricated by us-a biomaterial scaffold implanted with Schwann cells modified by the neurotrophin-3 (NT-3) gene and adult stem cells modified with the TrkC (receptor of NT-3) gene. More importantly, experimental evidence suggests that the novel artificial network can integrate with the host tissue and serve as an exogenous neuronal relay for signal transfer and functional improvement of SCI. PMID- 26850707 TI - Longevity on Antiretroviral Therapy for Children Living with HIV/AIDS--A Price to Pay for Success? PMID- 26850706 TI - Association between aspirin therapy and the outcome in critically ill patients: a nested cohort study. AB - BACKGROUND: Antiplatelet therapy may attenuate the undesirable effects of platelets on the inflammatory cascades in critical illness. The objective of this study was to evaluate the association between aspirin therapy during intensive care unit (ICU) stay and all-cause mortality. METHODS: This was a nested cohort study within two randomized controlled trials in which all enrolled patients (N = 763) were grouped according to aspirin intake during ICU stay. The primary endpoints were all-cause ICU mortality and hospital mortality. Secondary endpoints included the development of severe sepsis during the ICU stay, ICU and hospital length of stay and the duration of mechanical ventilation. Propensity score was used to adjust for clinically and statistically relevant variables. RESULTS: Of the 763 patients, 154 patients (20 %) received aspirin. Aspirin therapy was not associated with a reduction in ICU mortality (adjusted OR 1.18, 95 % CI 0.69-2.02, P = 0.55) nor with hospital mortality (adjusted OR 0.95, 95 % CI 0.61-1.50, P = 0.82). Aspirin use had no preferential association with mortality among any of the study subgroups. Additionally, aspirin therapy was associated with higher risk of ICU-acquired severe sepsis, and increased mechanical ventilation duration and ICU length of stay. CONCLUSION: Our study showed that the use of aspirin in critically ill patients was not associated with lower mortality, but rather with an increased morbidity. TRIAL REGISTRATION NUMBER: ISRCTN07413772 and ISRCTN96294863 . PMID- 26850708 TI - Closed-loop control in type 1 diabetes. PMID- 26850710 TI - Psychosocial dimensions of early-onset puberty and its treatment. PMID- 26850709 TI - Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial. AB - BACKGROUND: The safety and efficacy of continuous, multiday, automated glycaemic management has not been tested in outpatient studies of preadolescent children with type 1 diabetes. We aimed to compare the safety and efficacy of a bihormonal bionic pancreas versus conventional insulin pump therapy in this population of patients in an outpatient setting. METHODS: In this randomised, open-label, crossover study, we enrolled preadolescent children (aged 6-11 years) with type 1 diabetes (diagnosed for >=1 year) who were on insulin pump therapy, from two diabetes camps in the USA. With the use of sealed envelopes, participants were randomly assigned in blocks of two to either 5 days with the bionic pancreas or conventional insulin pump therapy (control) as the first intervention, followed by a 3 day washout period and then 5 days with the other intervention. Study allocation was not masked. The autonomously adaptive algorithm of the bionic pancreas received data from a continuous glucose monitoring (CGM) device to control subcutaneous delivery of insulin and glucagon. Conventional insulin pump therapy was administered by the camp physicians and other clinical staff in accordance with their established protocols; participants also wore a CGM device during the control period. The coprimary outcomes, analysed by intention to treat, were mean CGM-measured glucose concentration and the proportion of time with a CGM-measured glucose concentration below 3.3 mmol/L, on days 2-5. This study is registered with ClinicalTrials.gov, number NCT02105324. FINDINGS: Between July 20, and Aug 19, 2014, 19 children with a mean age of 9.8 years (SD 1.6) participated in and completed the study. The bionic pancreas period was associated with a lower mean CGM-measured glucose concentration on days 2-5 than was the control period (7.6 mmol/L [SD 0.6] vs 9.3 mmol/L [1.7]; p=0.00037) and a lower proportion of time with a CGM-measured glucose concentration below 3.3 mmol/L on days 2-5 (1.2% [SD 1.1] vs 2.8% [1.2]; p<0.0001). The median number of carbohydrate interventions given per participant for hypoglycaemia on days 1-5 (ie, glucose <3.9 mmol/L) was lower during the bionic pancreas period than during the control period (three [range 0-8] vs five [0-14]; p=0.037). No episodes of severe hypoglycaemia were recorded. Medium-to-large concentrations of ketones (range 0.6-3.6 mmol/dL) were reported on seven occasions in five participants during the control period and on no occasion during the bionic pancreas period (p=0.063). INTERPRETATION: The improved mean glycaemia and reduced hypoglycaemia with the bionic pancreas relative to insulin pump therapy in preadolescent children with type 1 diabetes in a diabetes camp setting is a promising finding. Studies of a longer duration during which children use the bionic pancreas during their normal routines at home and school should be done to investigate the potential for use of the bionic pancreas in real-world settings. FUNDING: The Leona M and Harry B Helmsley Charitable Trust and the US National Institute of Diabetes and Digestive and Kidney Diseases. PMID- 26850711 TI - Characterization of blooming algae and bloom-associated changes in the water quality parameters of traditional pokkali cum prawn fields along the South West coast of India. AB - In tropical shrimp farms, especially in traditional pokkali shrimp ponds, poor water quality management can lead to serious threats like heavy algal blooms and frequent disease outbreaks. An investigation regarding the frequent disease outbreaks in selected pokkali shrimp pond adjoining the Cochin backwaters has been conducted. Water quality parameters were analyzed during the study period. Results indicate a considerable fluctuation in the concentration of dissolved oxygen (DO) in the study in the shrimp farm where the algal bloom was observed. Poor water exchange along with nutrient loading from adjacent housing areas resulted in heavy algal bloom in the pond which led to hypoxic conditions in early morning and supersaturation of DO in the afternoon. It also led to considerably high alkaline pH. High levels of total ammonia nitrogen (TAN) were recorded in the sampling sites. Heavy algal bloom was observed throughout the study period in the selected pond especially in the summer. Anabaenopsis elenkinii and Merismopedia elagans which were the dominant species from the culture pond caused the bloom. Characterization and percentage distribution of bacteria present in the water and those associated with the algal blooms were carried out. The algae were found to support greater diversity of bacteria when compared to water. Pathogenic species like Aeromonas hydrophila and Vibrio parahaemolyticus were encountered in the study. Experimental challenge studies using Artemia as a model showed that the V. parahaemolyticus isolates were highly pathogenic. Hence, this study reveals how algal growth supports opportunistic pathogens in great diverse in a shrimp pond and causes frequent disease outbreaks under favourable conditions. PMID- 26850712 TI - Classification of riparian forest species and health condition using multi temporal and hyperspatial imagery from unmanned aerial system. AB - Riparian forests are critically endangered many anthropogenic pressures and natural hazards. The importance of riparian zones has been acknowledged by European Directives, involving multi-scale monitoring. The use of this very-high resolution and hyperspatial imagery in a multi-temporal approach is an emerging topic. The trend is reinforced by the recent and rapid growth of the use of the unmanned aerial system (UAS), which has prompted the development of innovative methodology. Our study proposes a methodological framework to explore how a set of multi-temporal images acquired during a vegetative period can differentiate some of the deciduous riparian forest species and their health conditions. More specifically, the developed approach intends to identify, through a process of variable selection, which variables derived from UAS imagery and which scale of image analysis are the most relevant to our objectives.The methodological framework is applied to two study sites to describe the riparian forest through two fundamental characteristics: the species composition and the health condition. These characteristics were selected not only because of their use as proxies for the riparian zone ecological integrity but also because of their use for river management.The comparison of various scales of image analysis identified the smallest object-based image analysis (OBIA) objects (ca. 1 m(2)) as the most relevant scale. Variables derived from spectral information (bands ratios) were identified as the most appropriate, followed by variables related to the vertical structure of the forest. Classification results show good overall accuracies for the species composition of the riparian forest (five classes, 79.5 and 84.1% for site 1 and site 2). The classification scenario regarding the health condition of the black alders of the site 1 performed the best (90.6%).The quality of the classification models developed with a UAS-based, cost-effective, and semi-automatic approach competes successfully with those developed using more expensive imagery, such as multi-spectral and hyperspectral airborne imagery. The high overall accuracy results obtained by the classification of the diseased alders open the door to applications dedicated to monitoring of the health conditions of riparian forest. Our methodological framework will allow UAS users to manage large imagery metric datasets derived from those dense time series. PMID- 26850713 TI - Permutation/randomization-based inference for environmental data. AB - Quantitative inference from environmental contaminant data is almost exclusively from within the classic Neyman/Pearson (N/P) hypothesis-testing model, by which the mean serves as the fundamental quantitative measure, but which is constrained by random sampling and the assumption of normality in the data. Permutation/randomization-based inference originally forwarded by R. A. Fisher derives probability directly from the proportion of the occurrences of interest and is not dependent upon the distribution of data or random sampling. Foundationally, the underlying logic and the interpretation of the significance of the two models vary, but inference using either model can often be successfully applied. However, data examples from airborne environmental fungi (mold), asbestos in settled dust, and 1,2,3,4-tetrachlorobenzene (TeCB) in soil demonstrate potentially misleading inference using traditional N/P hypothesis testing based upon means/variance compared to permutation/randomization inference using differences in frequency of detection (Deltaf d). Bootstrapping and permutation testing, which are extensions of permutation/randomization, confirm calculated p values via Deltaf d and should be utilized to verify the appropriateness of a given data analysis by either model. PMID- 26850714 TI - Eye movement abnormalities in a patient with Zellweger spectrum disorder. PMID- 26850716 TI - [Molecular analysis of an outbreak of Serratia marcescens and its possible connection with the use of a chlorhexidine solution]. PMID- 26850717 TI - [D68 enterovirus does exists in Spain]. PMID- 26850715 TI - Parkinsonism in a pair of monozygotic CADASIL twins sharing the R1006C mutation: a transcranial sonography study. AB - Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common hereditary cerebral small vessel disease, is caused by mutations in the NOTCH3 gene on chromosome 19. Clinical manifestations of CADASIL include recurrent transient ischemic attacks, strokes, cognitive defects, epilepsy, migraine and psychiatric symptoms. Parkinsonian features have variably been reported in CADASIL patients, but only a few patients showed a clear parkinsonian syndrome. We studied two patients, a pair of monozygotic twins, carrying the R1006C mutation of the NOTCH3 gene and affected by a parkinsonian syndrome. For the first time in CADASIL patients, we used transcranial sonography (TCS) to assess basal ganglia abnormalities. TCS showed a bilateral hyperechogenic pattern of substantia nigra in one twin, and a right hyperechogenic pattern in the other. In both patients, lenticular nuclei showed a bilateral hyperechogenic pattern, and the width of the third ventricle was slightly increased. The TCS pattern found in our CADASIL patients is characteristic neither for Parkinson's disease, nor for vascular parkinsonism and seems to be specific and related to the disease-specific pathological features. PMID- 26850718 TI - High prevalence of international ESBL CTX-M-15-producing Enterobacter cloacae ST114 clone in animals. AB - OBJECTIVES: The objective of this study was to characterize ESBL-producing Enterobacter cloacae isolated from animals and to compare their clonal distribution with that of human-related isolates. METHODS: Among 635 clinical E. cloacae from horses, dogs and cats collected in France between 2010 and 2013, 36 were resistant to ceftiofur as determined by disc diffusion. ESBL genes were identified by sequencing. Plasmids carrying ESBL-encoding genes were characterized by PCR-based replicon typing, S1-PFGE and Southern blotting. IncHI2 plasmids were subtyped using the plasmid double-locus sequence typing scheme and multiplex amplification of the hipA, smr0092 and smr0183 genes. All E. cloacae were typed by PFGE and MLST. ST clustering was analysed by eBURST. RESULTS: All 36 ceftiofur-resistant E. cloacae produced an ESBL. Their PFGE patterns formed 23 clusters of high similarity and 13 STs and were isolated from epidemiologically unrelated animals (14 horses, 11 dogs and 11 cats) distributed throughout France. ST114, the most prevalent clone in humans, was over-represented in animals (16/36) compared with other human-related clones detected here. The blaCTX-M-15 gene was dominant (66.7%) and mostly carried on IncHI2 plasmids (ST1 subtype). ST114 isolates always produced CTX-M-15. CONCLUSIONS: Most ESBL-producing E. cloacae from animals studied here (69.4%) belonged to potentially high-risk clones in humans, in particular ST114 (44.4%). These data raise questions and potential concerns about the transfer of E. cloacae between animals and humans. PMID- 26850719 TI - Dynamic interaction of colistin and meropenem on a WT and a resistant strain of Pseudomonas aeruginosa as quantified in a PK/PD model. AB - OBJECTIVES: Combination therapy can be a strategy to ensure effective bacterial killing when treating Pseudomonas aeruginosa, a Gram-negative bacterium with high potential for developing resistance. The aim of this study was to develop a pharmacokinetic/pharmacodynamic (PK/PD) model that describes the in vitro bacterial time-kill curves of colistin and meropenem alone and in combination for one WT and one meropenem-resistant strain of P. aeruginosa. METHODS: In vitro time-kill curve experiments were conducted with a P. aeruginosa WT (ATCC 27853) (MICs: meropenem 1 mg/L; colistin 1 mg/L) and a meropenem-resistant type (ARU552) (MICs: meropenem 16 mg/L; colistin 1.5 mg/L). PK/PD models characterizing resistance were fitted to the observed bacterial counts in NONMEM. The final model was applied to predict the bacterial killing of ARU552 for different combination dosages of colistin and meropenem. RESULTS: A model with compartments for growing and resting bacteria, where the bacterial killing by colistin reduced with continued exposure and a small fraction (0.15%) of the start inoculum was resistant to meropenem, characterized the bactericidal effect and resistance development of the two antibiotics. For a typical patient, a loading dose of colistin combined with a high dose of meropenem (2000 mg q8h) was predicted to result in a pronounced kill of the meropenem-resistant strain over 24 h. CONCLUSIONS: The developed PK/PD model successfully described the time course of bacterial counts following exposures to colistin and meropenem, alone and in combination, for both strains, and identified a dynamic drug interaction. The study illustrates the application of a PK/PD model and supports high-dose combination therapy of colistin and meropenem to overcome meropenem resistance. PMID- 26850720 TI - Single amino acid substitution Gly186Val in AdeS restores tigecycline susceptibility of Acinetobacter baumannii. AB - OBJECTIVES: Amino acid substitutions within the AdeRS two-component system are believed to result in overexpression of the AdeABC efflux pump and extensive resistance to antibiotics in clinical Acinetobacter baumannii isolates. However, the exact amino acid substitutions in AdeRS that cause overexpression of the AdeABC efflux pump remain unclear. We elucidated the role of amino acid substitutions in AdeRS by a complementation assay in an adeRS knockout strain of A. baumannii. METHODS: Five types of adeRS operon from tigecycline-resistant XDR A. baumannii (XDRAB) were cloned and introduced into the adeRS knockout strain to reverse its tigecycline susceptibility. RESULTS: Through shuffling gene segments among those five adeRS operons and performing site-directed mutagenesis, we found that the specific amino acid substitution Gly186Val in AdeS is crucial for reducing tigecycline susceptibility of A. baumannii. CONCLUSIONS: Our result demonstrates that a critical amino acid substitution in AdeS alters the AdeABC efflux pump-mediated tigecycline resistance of A. baumannii. PMID- 26850721 TI - Resistance and cross-resistance profile of the diaryltriazine NNRTI and candidate microbicide UAMC01398. AB - OBJECTIVES: The resistance development, cross-resistance to other NNRTIs and the impact of resistance on viral replicative fitness were studied for the new and potent NNRTI UAMC01398. METHODS: Resistance was selected by dose escalation and by single high-dose selection against a comprehensive panel of NNRTIs used as therapeutics and NNRTIs under investigation for pre-exposure prophylaxis of sexual HIV transmission. A panel of 27 site-directed mutants with single mutations or combinations of mutations involved in reverse transcriptase (RT) inhibitor-mediated resistance was developed and used to confirm resistance to UAMC01398. Cross-resistance to other NNRTIs was assessed, as well as susceptibility of UAMC01398-resistant HIV to diarylpyrimidine-resistant viruses. Finally, the impact of UAMC01398 resistance on HIV replicative fitness was studied. RESULTS: We showed that UAMC01398 has potent activity against dapivirine resistant HIV, that at least four mutations in the RT are required in concert for resistance and that the resistance profile is similar to rilpivirine, both genotypically and phenotypically. Resistance development to UAMC01398 is associated with a severe fitness cost. CONCLUSIONS: These data, together with the enhanced safety profile and good solubility in aqueous gels, make UAMC01398 an excellent candidate for HIV topical prevention. PMID- 26850722 TI - Proteomics reveals major components of oogenesis in the reproductive tract of sugar-fed Anopheles aquasalis. AB - Anopheles (Nyssorhynchus) aquasalis is a malaria vector mainly distributed along the coastal regions of South and Central America. In the absence of an effective vaccine against malaria, strategies for controlling the vector are the main tool for interrupting parasite transmission. Mechanisms of oogenesis and embryogenesis in anautogenous mosquitoes are mainly modulated by blood feeding. However, the expression, at the protein level, of genes involved in such mechanisms in sugar fed females is unknown. In this work, total protein extracts of the reproductive tract of female An. aquasalis that were fed sugar were analyzed using liquid chromatography followed by mass spectrometry for protein identification and bioinformatic tools for data mining. We identified 922 proteins expressed in the organ, and using several databases, we attributed biological meaning for several of them. Remarkably, nine proteins involved in oogenesis were identified in females fed sugar. Putative vitellogenins, vitellogenin receptor, lipid storage droplet, transferrin, ferritin, and apolipoprotein, identified here, are proteins involved in egg development. Proteins involved in embryonic development, such as paxillin, exuperantia, several growth factors, and dorsal switch protein, were identified. Interestingly, in this study, we identified 15 peptidases of various classes such as aminopeptidases, carboxypeptidases, serine protease, cathepsin, and metalloprotease that could potentially interact with male seminal components. Here, we demonstrated that the reproductive tract of female An. aquasalis fed on sugar expresses proteins involved in oogenesis and embryonic development. These findings reveal unknown aspects of the physiology of this organ under the given nutritional conditions. PMID- 26850724 TI - Chinese herbal medicine Xiaoji decoction inhibited growth of lung cancer cells through AMPKalpha-mediated inhibition of Sp1 and DNA methyltransferase 1. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoji decoction (XJD), which was considered as a Chinese herbal prescription, has been used for cancer treatment, especially lung cancer, for decades to improve quality of life and prolong the patient survival. However, the molecular mechanisms underlying the therapeutic potential have not been well elucidated. MATERIALS AND METHODS: The cell viability was examined by MTT assays. The phosphorylation and expression of AMP-activated protein kinase alpha (AMPKalpha), DNA methyltransferase 1 (DNMT1) and transcription factor Sp1 proteins were assessed by Western Blot. Exogenous expression of Sp1 and DNMT1 were performed by transient transfection methods. The effects of XJD on the growth of xenograft tumors were evaluated by in vivo bioluminescence imaging. RESULTS: We showed that XJD inhibited growth of human non small cell lung cancer (NSCLC) cells in vitro. We also found that XJD increased phosphorylation of AMPKalpha and inhibited protein expression of DNTM1, the latter was not observed in the presence of the inhibitor of AMPK (compound C). Overexpression of DNTM1 reversed the effect of XJD on cell growth. In addition, XJD decreased Sp1 protein expression, which was eliminated by compound C. Conversely, exogenous expressed Sp1 abrogated XJD-inhibited DNTM1 protein expression. Interestingly, exogenous expression of DNMT1 feedback antagonized the XJD-induced phosphorylation of AMPKalpha. In in vivo studies, we found that XJD inhibited tumor growth in xenograft nude mice model, which was accompanied by induction of phosphorylation of AMPKalpha and suppression of DNMT1 protein from xenograft tumors. CONCLUSION: Our results show that XJD inhibits NSCLC cell growth via AMPKalpha-mediated inhibition of transcription of Sp1, followed by the reduction of DNMT1 expression both in vitro and in vivo. The negative feedback regulation loop of AMPKalpha further demonstrates the critical role of DNMT1 in mediating the overall effects of XJD in this process. This study unveils novel molecular mechanism by which XJD controls NSCLC cell growth. PMID- 26850723 TI - Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face. AB - Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events. PMID- 26850726 TI - Walking the tightrope: communicating overdiagnosis in modern healthcare. PMID- 26850725 TI - Circulating angiopoietin-like protein 8 (betatrophin) association with HsCRP and metabolic syndrome. AB - BACKGROUND: ANGPTL8 also called betatrophin is a regulator of lipid metabolism through its interaction with ANGPTL3. It has also been suggested to play a role in insulin resistance and beta-cell proliferation. Based on its function, we hypothesized that ANGPTL8 will play a role in Metabolic Syndrome (MetS). To test this hypothesis we designed this study to measure ANGPTL8 level in subjects with MetS as well as its association with high sensitivity C-reactive protein (HsCRP) level in humans. METHODS: ANGPTL8 level was measured using ELISA in subjects with MetS as well as their controls, a total of 1735 subjects were enrolled. HsCRP was also measured and its association with ANGPTL8 was examined. RESULTS: ANGPTL8 level was higher in subjects with MetS 1140.6 (171.9-11736.1) pg/mL compared to 710.5 (59.5-11597.2) pg/mL in the controls. Higher levels of ANGPTL8 were also observed with the sequential increase in the number of MetS components (p value = <0.0001). ANGPTL8 showed strong positive correlation with HsCRP (r = 0.15, p value = <0.0001). Stratifying the population into tertiles according to the level of HsCRP showed increased ANGPTL8 level at higher tertiles of HsCRP in the overall population (p value = <0.0001).A similar trend was also observed in MetS and non-MetS subjects as well as in non-obese and obese subjects. Finally, multiple logistic regression models adjusted for age, gender, ethnicity and HsCRP level showed that subjects in the highest tertiles of ANGPTL8 had higher odds of having MetS (odd ratio [OR] = 2.3, 95 % confidence interval [CI] = (1.6-3.1), p value <0.0001. CONCLUSION: In this study we showed that ANGPTL8 is increased in subjects with MetS and it was significantly associated with HsCRP levels in different subgroups highlighting its potential role in metabolic and inflammatory pathways. PMID- 26850727 TI - Women's Health Behaviours and Psychosocial Well-Being by Cardiac Rehabilitation Program Model: A Randomized Controlled Trial. AB - BACKGROUND: Cardiac rehabilitation (CR) is associated with significantly lower mortality and improved psychosocial well-being. However, women are less likely to participate than men. This trial tested whether participation in women-only CR results in better health behaviours and psychosocial outcomes than do other models. METHODS: Cardiac Rehabilitation for her Heart Event Recovery (CR4HER) was a single-blind randomized trial with 3 parallel arms. Low-risk cardiac patients were recruited from 6 sites in Ontario. Consenting participants completed surveys assessing health behaviours (physical activity, diet, medication adherence, smoking) and psychosocial well-being (social support, quality of life, depressive symptoms) and wore pedometers for 7 days. After intake assessment, eligible participants were randomized to mixed-sex, women-only, or home-based CR. Participants were mailed follow-up surveys and pedometers 6 months later. RESULTS: One hundred sixty-nine patients were randomized, and 116 (68.6%) were retained. Self-reported physical activity increased among women in mixed-sex and women-only CR groups (per protocol and as treated, P < 0.05). Diet improved among women in women-only CR groups (as treated, P < 0.05). Quality of life improved among women in mixed-sex (per protocol and as treated, P < 0.05) and women-only CR groups (per protocol, P < 0.05; as treated, P < 0.01). After testing, women in the mixed-sex CR group had higher anxiety symptoms than did those in the women only group (per protocol, P = 0.017), and those in the mixed-sex CR group had higher depressive symptoms than did those in the women-only group (as treated, P = 0.001). Analyses adjusted for confounding variables revealed no significant differences in any outcome by model. Post hoc equivalency tests were computed on a per-protocol basis, and all outcomes were equivalent by model. CONCLUSIONS: Behavioural and psychosocial outcomes were largely equivalent regardless of model; however, women-only programs may confer an advantage for anxiety and depressive symptoms. PMID- 26850729 TI - Psychological distress of parents in conflict areas: the mediating role of war atrocities, normative stressors and family resources. AB - BACKGROUND: Despite the ongoing controversy regarding which types of stressors or resources contribute to psychological distress, there has been little research examining the relationship between war trauma, normative stressors, family resources for management and psychopathology. AIMS: This study investigated the differences between mothers and fathers in psychological distress, normative stressors and war atrocities experienced, and family's resources for management. It was hypothesized that a combination of risk variables and protective variables would be predictive of psychological distress in parents. METHODS: Questionnaires were used with 205 Palestinian parents from Gaza Strip. RESULTS: Mothers had more psychiatric disorders than did fathers. Although, mothers and fathers were exposed to comparable levels of normative stressors, mothers concerns about intrafamily strains, and family legal violations were greater than they were for fathers. Results revealed that fathers possess a larger repertoire of resources for management when compared to mothers reflected in esteem and communication, mastery and health, extended family social support and financial well-being. However, mastery and health seem to buffer the effect of war traumas and normative stressors on neuroticism in both parents. CONCLUSION: The different patterns of predictor-outcome relations have practical as well as theoretical implications. PMID- 26850728 TI - miR-320a affects spinal cord edema through negatively regulating aquaporin-1 of blood-spinal cord barrier during bimodal stage after ischemia reperfusion injury in rats. AB - BACKGROUND: Spinal cord edema is a serious complication and pathophysiological change after ischemia reperfusion (IR) injury. It has been demonstrated closely associated with bimodal disruption of blood-spinal cord barrier (BSCB) in our previous work. Aquaporin (AQP)1 plays important but contradictory roles in water homeostasis. Recently, microRNAs (miRs) effectively regulate numerous target mRNAs during ischemia. However, whether miRs are able to protect against dimodal disruption of BSCB by regulating perivascular AQP1 remains to be elucidated. RESULTS: Spinal water content and EB extravasation were suggested as a bimodal distribution in directly proportion to AQP1, since all maximal changes were detected at 12 and 48 h after reperfusion. Further TEM and double immunofluorescence showed that former disruption of BSCB at 12 h was attributed to cytotoxic edema by up-regulated AQP1 expressions in astrocytes, whereas the latter at 48 h was mixed with vasogenic edema with both endothelial cells and astrocytes involvement. Microarray analysis revealed that at 12 h post-injury, ten miRs were upregulated (>2.0 fold) and seven miRs were downregulated (<0.5 fold) and at 48 h, ten miRs were upregulated and eleven were downregulated compared to Sham-operated controls. Genomic screening and luciferase assays identified that miR-320a was a potential modulator of AQP1 in spinal cord after IR in vitro. In vivo, compared to rats in IR and negative control group, intrathecal infusion of miR-320a mimic attenuated IR-induced lower limb motor function deficits and BSCB dysfunction as decreased EB extravasation and spinal water content through down-regulating AQP1 expressions, whereas pretreated with miR-320a AMO reversed above effects. CONCLUSION: These findings indicate miR-320a directly and functionally affects spinal cord edema through negatively regulating AQP1 of BSCB after IR. PMID- 26850730 TI - Supra-physiological dose of testosterone induces pathological cardiac hypertrophy. AB - Testosterone and androgenic anabolic steroids have been misused for enhancement of physical performance despite many reports on cardiac sudden death. Although physiological level of testosterone provided many regulatory benefits to human health, including the cardiovascular function, supra-physiological levels of the hormone induce hypertrophy of the heart with unclear contractile activation. In this study, dose- and time-dependent effects of high-testosterone treatment on cardiac structure and function were evaluated. Adult male rats were divided into four groups of testosterone treatment for 0, 5, 10, and 20 mg/kg BW for 4, 8, or 12 weeks. Increases in both percentage heart:body weight ratio and cardiomyocyte cross-sectional area in representing hypertrophy of the heart were significantly shown in all testosterone-treated groups to the same degree. In 4-week-treated rats, physiological cardiac hypertrophy was apparent with an upregulation of alpha-MHC without any change in myofilament contractile activation. In contrast, pathological cardiac hypertrophy was observed in 8- and 12-week testosterone treated groups, as indicated by suppression of myofilament activation and myocardial collagen deposition without transition of MHC isoforms. Only in 12 week testosterone-treated group, eccentric cardiac hypertrophy was demonstrated with unaltered myocardial stiffness, but significant reductions in the phosphorylation signals of ERK1/2 and mTOR. Results of our study suggest that the outcome of testosterone-induced cardiac hypertrophy is not dose dependent but is rather relied on the factor of exposure to duration in inducing maladaptive responses of the heart. PMID- 26850731 TI - Multiwalled Carbon Nanotubes-Dispersive Solid-Phase Extraction Coupled with UPLC ESI-MS-MS for Simultaneous Determination of 10 Illegal Adulterants in Antihypertensive Functional Foods. AB - A reliable method for simultaneous determination of 10 illegal adulterants including chlortalidone, hydrochlorothiazide, indapamide, metoprolol, nifedipine, nimodipine, nitrendipine, reserpine, triamterene and valsartan in antihypertensive functional foods by ultra-high-performance liquid chromatography coupled with electrospray ionization-tandem mass spectrometry is presented in this article. The target chemicals were extracted with acetonitrile ultrasonically and cleaned up using multiwalled carbon nanotubes-dispersive solid phase extraction. The separation was performed on a Waters ACQUITY UPLC BEH C18 Column (2.1 * 100 mm, 1.7 um) with acetonitrile, 0.1% formic acid and 10 mmol/L ammonium acetate solution as mobile phase at a flow rate of 0.2 mL/min. Multiple reaction monitoring was applied for detection and sildenafil was used as the internal standard. The correlation coefficients of the method were >0.995, with the limits of detection of 0.022-0.30 ng/mL and the limits of quantification of 0.075-0.99 ng/mL. The interday and intraday relative standard deviations were <9.77% and the recoveries were in the range of 85.8-109%. The established method has been applied for the analysis of real samples, and reserpine was detected in a tonic wine sample with a content of 60.1 +/- 3.2 mg/L. PMID- 26850732 TI - A Validated Stability-Indicating and Stereoselective HPLC Method for the Determination of Lenalidomide Enantiomers in Bulk Form and Capsules. AB - A simple, rapid and stability-indicating chiral HPLC (CHR-HPLC) method was designed for the enantiomeric separation of lenalidomide (LDM) in the presence of its degradation products. LDM was exposed to different accelerated stress factors. The degradation products were well resolved from the pure drug enantiomers. Separation of the LDM enantiomers was achieved on a LUX 5U cellulose 2 chiral column (250 * 4.6 mm i.d.) with a mobile phase consisting of methanol : glacial acetic acid : triethyl amine (100 : 0.01 : 0.01, v/v/v) at a flow rate of 1.2 mL/min. The detection wavelength was 220 nm, and ornidazole was the internal standard. The chiral method was validated in terms of its specificity, linearity, range, precision and accuracy as well as solution stability, robustness, limit of detection and limit of quantification. The calibration curve was linear for concentrations ranging from 2 to 1,000 ng/mL (r= 0.9999) for both LDM enantiomers. The proposed method, which met International Conference on Harmonization/Food and Drug Administration regulatory requirements, was utilized successfully for the determination of LDM in bulk and in capsules with acceptable accuracy and precision; the label demand percentages were 100.09 +/- 0.80 and 99.97 +/- 0.93 for the S-(-) and R-(+)-LDM enantiomers, respectively. Based on these results, this method should have great value when applied to quality control and stability studies of LDM. PMID- 26850733 TI - Potential of Entomopathogenic Fungi as Biological Control Agents of Diamondback Moth (Lepidoptera: Plutellidae) and Compatibility With Chemical Insecticides. AB - The objectives were to evaluate the efficiency of entomopathogenic fungi against Plutella xylostella (L.) and the compatibility of the most virulent isolates with some of the insecticides registered for use on cabbage crops. Pathogenicity tests used isolates of Beauveria bassiana, Metarhizium rileyi, Isaria fumosorosea, Isaria sinclairii, and Lecanicillium muscarium standardized at a concentration of 10(7) conidia/ml. Cabbage leaf discs were immersed in these suspensions, and after evaporation of the excess water, were placed 10 second-instar larvae of P. xylostella, totaling 10 leaf discs per treatment. Mortality was assessed 7 d after treatment, and the isolates that caused mortality>80% were used to estimate LC50 and LT50. The compatibilities of the most virulent isolates and the insecticides were tested from the mixture of these into the culture medium, and after solidifying, the medium was inoculated with an aliquot of the isolated suspension. The following parameters were evaluated: growth of the colony, number and viability of conidia after 7 d. The isolated IBCB01, IBCB18, IBCB66, and IBCB87 of B. bassiana, LCMAP101 of M. rileyi, and ARSEF7973 of I. sinclairii caused mortality between 80 and 100%, with LC50 and LT50 between 2.504 to 6.775*10(4) conidia/ml and 52.22 to 112.13 h, respectively. The active ingredients thiamethoxam and azadirachtin were compatible with the entomopathogenic fungi. The results suggest that the use of these isolates is an important alternative in the pesticidal management of P. xylostella, with the possible exception of the associated use of chemical controls using the active ingredients thiamethoxam or azadirachtin. PMID- 26850734 TI - Vesical Artery Embolization in Haemorrhagic Cystitis in Children. AB - Haemorrhagic cystitis is an uncommon and, in its severe form, potentially life threatening complication of haematopoietic stem cell transplantation or cancer therapy in children. The severe form involves macroscopic haematuria with blood clots, urinary obstruction and/or renal impairment. There are many therapeutic options to treat acute haemorrhage, but only recombinant factor VII has a high level of clinical evidence in children. Supraselective vesical artery embolization (SVAE) is an increasingly used therapeutic procedure for controlling haemorrhage in adults, but is less commonly used in children. This might be due to several factors, such as the invasive nature of the procedure, lack of appropriate medical experience and possible long-term side effects. We present three cases of children successfully treated by means of effective SVAE. PMID- 26850735 TI - Restoring effect of selenium on the molecular content, structure and fluidity of diabetic rat kidney brush border cell membrane. AB - Diabetic kidney disease (DKD) is a dominant factor standing for kidney impairments during diabetes. In this study, attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was used to disclose the diabetes induced structural changes in the kidney and evaluate the effects of selenium on diabetes. The increase in the area of the olefinic band indicated increased amount of lipid peroxidation end products in diabetic kidney brush border cell membrane. Moreover, saturated lipid content of this cell membrane considerably diminished. DKD was found to disrupt lipid order and cause a decrease in membrane dynamics. However, the administration of selenium at low and medium doses was shown to improve these conditions by changing the lipid contents toward control values, restoring the ordered structure of the lipids and membrane dynamics. Curve-fitting and artificial neural network (ANN) analyses of secondary structures of proteins demonstrated a relative increase in alpha-helix and reduction in the beta-sheet during diabetes in comparison to the control group, which were ameliorated following selenium treatment at low and medium doses. These findings were further confirmed by applying hierarchical cluster analysis (HCA) and principal component analysis (PCA). A clear separation of the experimental groups was obtained with high heterogeneity in the lipid and protein regions. These chemometric analyses showed that the low and medium doses of selenium-treated diabetic groups are successfully segregated from the diabetic group and clustered closer to the control. The study suggests that medium and, more predominantly, low-dose selenium treatment can be efficient in eliminating diabetes-induced structural alterations. PMID- 26850736 TI - Membrane-binding properties of gating modifier and pore-blocking toxins: Membrane interaction is not a prerequisite for modification of channel gating. AB - Many venom peptides are potent and selective inhibitors of voltage-gated ion channels, including channels that are validated therapeutic targets for treatment of a wide range of human diseases. However, the development of novel venom peptide-based therapeutics requires an understanding of their mechanism of action. In the case of voltage-gated ion channels, venom peptides act either as pore blockers that bind to the extracellular side of the channel pore or gating modifiers that bind to one or more of the membrane-embedded voltage sensor domains. In the case of gating modifiers, it has been debated whether the peptide must partition into the membrane to reach its binding site. In this study, we used surface plasmon resonance, fluorescence spectroscopy and molecular dynamics to directly compare the lipid-binding properties of two gating modifiers (MU-TRTX Hd1a and ProTx-I) and two pore blockers (ShK and KIIIA). Only ProTx-I was found to bind to model membranes. Our results provide further evidence that the ability to insert into the lipid bilayer is not a requirement to be a gating modifier. In addition, we characterised the surface of ProTx-I that mediates its interaction with neutral and anionic phospholipid membranes and show that it preferentially interacts with anionic lipids. PMID- 26850737 TI - Validating lipid force fields against experimental data: Progress, challenges and perspectives. AB - Biological membranes display a great diversity in lipid composition and lateral structure that is crucial in a variety of cellular functions. Simulations of membranes have contributed significantly to the understanding of the properties, functions and behaviour of membranes and membrane-protein assemblies. This success relies on the ability of the force field used to describe lipid-lipid and lipid-environment interactions accurately, reproducibly and realistically. In this review, we present some recent progress in lipid force-field development and validation strategies. In particular, we highlight how a range of properties obtained from various experimental techniques on lipid bilayers and membranes, can be used to assess the quality of a force field. We discuss the limitations and assumptions that are inherent to both computational and experimental approaches and how these can influence the comparison between simulations and experimental data. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26850738 TI - Atypical Structural Connectome Organization and Cognitive Impairment in Young Survivors of Acute Lymphoblastic Leukemia. AB - Survivors of pediatric acute lymphoblastic leukemia (ALL) are at increased risk for cognitive impairments that disrupt everyday functioning and decrease quality of life. The specific biological mechanisms underlying cognitive impairment following ALL remain largely unclear, but previous studies consistently demonstrate significant white matter pathology. We aimed to extend this literature by examining the organization of the white matter connectome in young patients with a history of ALL treated with chemotherapy only. We applied graph theoretical analysis to diffusion tensor imaging obtained from 31 survivors of ALL age 5-19 years and 39 matched healthy controls. Results indicated significantly lower small-worldness (p = 0.007) and network clustering coefficient (p = 0.019), as well as greater cognitive impairment (p = 0.027) in the ALL group. Regional analysis indicated that clustered connectivity in parietal, frontal, hippocampal, amygdalar, thalamic, and occipital regions was altered in the ALL group. Random forest analysis revealed a model of connectome and demographic variables that could automatically classify survivors of ALL as having cognitive impairment or not (accuracy = 0.89, p < 0.0001). These findings provide further evidence of brain injury in young survivors of ALL, even those without a history of central nervous system (CNS) disease or cranial radiation. Efficiency of local information processing, reorganization of hub connectivity, and cognitive reserve may contribute to cognitive outcome in these children. Certain connectome properties showed U-shaped relationships with cognitive impairment suggesting an optimal range of regional connectivity. PMID- 26850739 TI - Endovascular Aneurysm Sealing Is Associated With Reduced Radiation Exposure and Procedure Time Compared With Standard Endovascular Aneurysm Repair. AB - PURPOSE: To compare indirect measures of radiation exposure and operating time between endovascular aneurysm sealing (EVAS) and endovascular aneurysm repair (EVAR) for the treatment of abdominal aortic aneurysm (AAA). METHODS: The study compared 32 consecutive patients (mean age 78 years; 21 men) with AAA who underwent standard EVAS with 32 consecutive patients (mean age 78 years; 25 men) treated with EVAR between November 2013 and May 2015. Electronic medical records and image archiving databases were interrogated to retrieve relevant information and scans. Screening time and dose area product (DAP) were the primary outcome measures. Data are presented as median and interquartile range (IQR). Correlations were tested with the Spearman rank coefficient (rho). RESULTS: The screening time was shorter in EVAS than in EVAR [16 (IQR 14, 20) vs 32 (IQR 26, 38) minutes; p<0.001]. DAP was lower in EVAS than in EVAR [54 (IQR 42, 77) vs 111 (IQR 75, 157) Gy?cm(2); p<0.001]. Digital subtraction angiography delivered 20% (IQR 15%, 28%) of the DAP in EVAS compared with 14% (IQR 11%, 19%) in EVAR (p<0.001), but the absolute time used on digital subtraction was marginally lower in EVAS than in EVAR [1.07 (IQR 0.52, 1.23) vs 1.19 (IQR 0.70, 1.39) minutes; p=0.037]. The operating time was shorter for EVAS [121 (IQR 105, 146) vs 162 (IQR 145,186) minutes; p<0.001]. There was a moderate correlation between DAP and screening time (rho=0.597, p<0.001), fluoroscopy time (rho=0.595, p<0.001), digital subtraction time (rho=0.301, p=0.015), and operating time (rho=0.512, p<0.001). CONCLUSION: EVAS is associated with reduced radiation exposure and operating room usage compared with EVAR, which may have safety and financial implications. PMID- 26850740 TI - Improved Delivery of Fat From Human Breast Milk via Continuous Tube Feeding. AB - BACKGROUND: Human breast milk is used sparingly in infants with intestinal failure due to observations from studies using syringe pumps that show loss of macronutrients with continuous feeding. Because of the potential benefits of using human milk, we sought to assess macronutrient losses using human milk as continuous tube feeds as done in the inpatient and home setting using a feeding bag and pump. METHODS: Using in vitro simulations of human milk to assess macronutrient losses with continuous tube feeds, hourly samples were analyzed using the SpectraStar Near-Infrared Analyzer (Unity Scientific, Columbia, MD). Effects of agitation and positional changes of the feeding bag on macronutrient delivery were investigated in 249 total samples. Pairwise comparisons were performed using repeated-measures analysis of variance. RESULTS: Significant fat losses were observed at all rates at hours 1-4, averaging to 73% at 5 mL/h. Caloric losses correlated strongly with fat losses. Significant gains in the fat content (+116% at hour 4 at 5 mL/h) were seen in the preinfusion aliquots (feeding bags). Horizontal positioning and continuous agitation of the feeding bag only partially limited fat losses. Fat delivery at 5 mL/h was significantly enhanced to 87% when the feeding bag was placed in an inverted position and improved further up to 98% with higher infusion rates. No carbohydrates and proteins losses were seen. CONCLUSIONS: Enabling the delivery of the human milk from the top of the feeding bag optimizes fat delivery and limits losses. Such top infusing feeding bags should be developed and could decrease healthcare costs for intestinal rehabilitation programs. PMID- 26850741 TI - Prevalence, Outcomes, and Management of Enteral Tube Feeding Intolerance: A Retrospective Cohort Study in a Tertiary Center. AB - BACKGROUND: Enteral tube feeding (ETF) is the most common form of artificial feeding in hospitalized patients, and the development of intolerance (ETFI) is the most common complication. This study aimed to determine the prevalence of ETFI, the clinical consequences, and the current management approach to ETFI in hospitalized adult patients. MATERIALS AND METHODS: Adult patients receiving ETF were identified from a prospective database in the Nutrition Services at Auckland City Hospital. Further information was obtained by the review of clinical records for a 12-month period, up to December 2014. RESULTS: The prevalence of ETFI was 33% among 754 patients. ETFI more frequently occurred in the intensive care unit ( P < .05). Patients with ETFI were less likely to reach their feeding goal rate ( P < .01). Multivariate analysis showed that younger age, certain specialties, and acute mesenteric ischemia were independent predictors of ETFI ( P < .05). The management of ETFI was highly variable. Medication was the most common treatment, while changes in the feeding protocol such as reducing infusion rate and stopping and changing the route of ETF were also frequently attempted. CONCLUSION: ETFI is a frequent problem in adult hospitalized patients receiving ETF, and it is associated with poor clinical outcomes such as inadequate nutrition and complications of feeding. While the pathophysiology is poorly understood, there also appears to be no standard evidence-based treatment. Studies investigating the mechanisms and optimized management are therefore indicated. PMID- 26850743 TI - Bilateral and symmetric isolated dorsospinal arteries with prominent anterior radiculomedullary contribution. AB - We present the case of a 15-year-old girl with a left T7 spinal epidural arteriovenous fistula (SEAVF), in whom bilateral and symmetric isolated T9 dorsospinal arteries (DAs) were incidentally documented, each providing a significant contribution to the anterior spinal artery. Recognizing the existence of isolated DAs of direct aortic origin is critical, both for the diagnostic evaluation and for the management of spinal vascular diseases. Notably, isolated DAs tend to branch off significant radiculomedullary arteries, which vascularize the normal spinal cord but have also been shown to supply spinal vascular malformations. PMID- 26850742 TI - Metabolic assessment of E. coli as a Biofactory for commercial products. AB - Metabolic engineering uses microorganisms to synthesize chemicals from renewable resources. Given the thousands of known metabolites, it is unclear what valuable chemicals could be produced by a microorganism and what native and heterologous reactions are needed for their synthesis. To answer these questions, a systematic computational assessment of Escherichia coli's potential ability to produce different chemicals was performed using an integrated metabolic model that included native E.coli reactions and known heterologous reactions. By adding heterologous reactions, a total of 1777 non-native products could theoretically be produced in E. coli under glucose minimal medium conditions, of which 279 non native products have commercial applications. Synthesis pathways involving native and heterologous reactions were identified from eight central metabolic precursors to the 279 non-native commercial products. These pathways were used to evaluate the dependence on, and diversity of, native and heterologous reactions to produce each non-native commercial product, as well as to identify each product's closest central metabolic precursor. Analysis of the synthesis pathways (with 5 or fewer reaction steps) to non-native commercial products revealed that isopentenyl diphosphate, pyruvate, and oxaloacetate are the closest central metabolic precursors to the most non-native commercial products. Additionally, 4 hydroxybenzoate, tyrosine, and phenylalanine were found to be common precursors to a large number of non-native commercial products. Strains capable of producing high levels of these precursors could be further engineered to create strains capable of producing a variety of commercial non-native chemicals. PMID- 26850744 TI - Intermittent Brugada Pattern in Relation to Changes in Body Temperature. PMID- 26850745 TI - Degree of Anticoagulation Control in Patients With Atrial Fibrillation in Spain: Need to Minimize Biases and Contextualize Results. Response by Anguita Sanchez et al. PMID- 26850746 TI - Omega-3 fatty acids do not alter P-wave parameters in electrocardiogram or expression of atrial connexins in patients undergoing coronary artery bypass surgery. AB - AIMS: We previously reported omega-3 polyunsaturated fatty acids (n-3PUFAs) supplementation does not reduce atrial fibrillation (AF) following coronary artery bypass graft (CABG) surgery. The aim of the present study is to evaluate the impact of n-3 PUFAs on electrocardiogram (ECG) atrial arrhythmic markers and compare with expression of gap-junction proteins, Connexins. METHODS AND RESULTS: Subset of clinical trial subjects with right atrial sampling during CABG surgery included. Twelve-lead ECG performed at recruitment and at surgery [after supplementation with n-3 PUFA (~1.8 g/day) or matched placebo] for ~14 days. Electrocardiograms analysed for maximum P-wave duration (P-max) and difference between P-max and minimum P-wave duration, P-wave dispersion (PWD). Right atrial specimens analysed for expression of Connexins 40 and 43 using real-time quantitative polymerase chain reaction (qPCR) and western blot. Serum levels of n 3 PUFA at baseline, at surgery, and atrial tissue levels at surgery collated from file. Postoperative AF was quantified by analysing data from stored continuous electrograms. A total of 61 patients (n-3 PUFA 34, Placebo 27) had ECG analysis and AF burden, of which 52 patients (26 in each group) had qPCR and 16 (8 in each group) had western blot analyses for Connexins 40 and 43. No difference between the two groups in ECG parameters or expression of Connexin 40 or 43. P-wave dispersion in the preoperative ECG independently predicted occurrence of AF following CABG surgery. CONCLUSIONS: Omega-3 polyunsaturated fatty acids supplementation does not alter pro-arrhythmic P-wave parameters in ECG or connexin expression in human atrium with no effect on the incidence of AF following CABG surgery. PMID- 26850748 TI - Combined remote magnetic navigation and ultra-high-density mapping (RhythmiaTM) in slow pathway ablation. PMID- 26850747 TI - Effect of experimental coronary sinus ligation on myocardial structure and function in the presence or absence of structural heart disease: an insight for the interventional electrophysiologist. AB - AIMS: To study the effect of coronary sinus (CS) occlusion on normal hearts and hearts with structural disease. METHODS AND RESULTS: We included 32 dogs, divided into 4 groups: (1) CS ligation (CSL): subjected to CSL; (2) control group: no intervention; (3) MI-CSL group: subjected to myocardial infarction (MI) induction followed by CSL after 1 week; and (4) MI-control group: subjected to MI induction, then open thoracotomy after 1 week without CSL. Electrocardiography, echocardiography, histopathology, and immunohistochemistry were done before and after CSL. In CSL group, there were no significant electrocardiographic or echocardiographic changes after CSL, although there was interstitial oedema that decreased after 1 week with the appearance of Thebesian vessels and positive staining for vascular endothelial growth factor. In MI-CSL group, there was significant increase in left ventricular (LV) end-systolic diameter (P = 02), decrease in LV fractional shortening (P = 0.0001), and LV ejection fraction (P = 0.002) in comparison with MI-control group, associated with severe myocardial degeneration. CONCLUSION: Acute CS occlusion could be compensated in normal hearts, but may be detrimental in the presence of structural heart disease. PMID- 26850749 TI - Giant epsilon waves in 12 leads in a patient with severe arrhythmogenic cardiomyopathy. PMID- 26850750 TI - An innovative fixed-pole numerical approximation for fractional order systems. AB - A novel numerical approximation scheme is proposed for fractional order systems by the concept of identification. An identical equation is derived firstly, from which one can obtain the exact state space model of fractional order systems. It reveals the nature of the approximation problem, and then provides an effective scheme to obtain the desired model. This research project also focuses on solving a knotty but crucial issue, i.e., the initial value problem of fractional order systems. The results generated by the study prove that it can reduce to the Caputo case by selecting some specific initial values. A careful simulation study is reported to illustrate the effectiveness of the proposed scheme. To exhibit the superiority clearly, the results are compared with that of the published fixed-pole finite model method. PMID- 26850751 TI - Stability analysis of autonomous space systems in the presence of large disturbances: A Lyapunov-based constrained control strategy. AB - The research addresses a Lyapunov-based constrained control strategy to deal with the autonomous space system in the presence of large disturbances. The aforementioned autonomous space system under control is first represented through a dynamics model and subsequently the proposed control strategy is fully investigated with a focus on the three-axis detumbling and the corresponding pointing mode control approaches. The three-axis detumbling mode control approach is designed to deal with the unwanted angular rates of the system to be zero, while the saturations of the actuators are taken into consideration. Moreover, the three-axis pointing mode control approach is designed in the similar state to deal with the rotational angles of the system to be desirable. The contribution of the research is mathematically made to propose a control law in connection with a new candidate of Lyapunov function to deal with the rotational angles and the related angular rates of the present autonomous space system with respect to state-of-the-art. A series of experiments are carried out to consider the efficiency of the proposed control strategy, as long as a number of benchmarks are realized in the same condition to verify and guarantee the strategy performance in both modes of control approaches. PMID- 26850752 TI - Iterated non-linear model predictive control based on tubes and contractive constraints. AB - This paper presents a predictive control algorithm for non-linear systems based on successive linearizations of the non-linear dynamic around a given trajectory. A linear time varying model is obtained and the non-convex constrained optimization problem is transformed into a sequence of locally convex ones. The robustness of the proposed algorithm is addressed adding a convex contractive constraint. To account for linearization errors and to obtain more accurate results an inner iteration loop is added to the algorithm. A simple methodology to obtain an outer bounding-tube for state trajectories is also presented. The convergence of the iterative process and the stability of the closed-loop system are analyzed. The simulation results show the effectiveness of the proposed algorithm in controlling a quadcopter type unmanned aerial vehicle. PMID- 26850753 TI - Alcohol-related driving in China: Countermeasure implications of research conducted in two cities. AB - OBJECTIVE: Drunk driving (blood alcohol concentration (BAC) 80mg/100ml) was upgraded to become a criminal offence under China's Criminal Law in May 2011. While this had a major road safety benefit, there was still a high level of alcohol related crashes and fatalities. This paper develops recommendations based on a programme of research undertaken in 2012 that examined the perceptions of general motor vehicle drivers, convicted drunk driving offenders and traffic police about drinking and driving and law enforcement in the cities of Guangzhou and Yinchuan. Alcohol misuse problems were also explored using the Alcohol Use Disorders Identification Test (AUDIT). This paper integrates the findings to examine existing problems in alcohol management, law enforcement, education and rehabilitation and provides recommendations for addressing alcohol-related driving in China. METHODS: A multi-study cross-sectional research programme was conducted in two Chinese cities involving general drivers, drunk driving offenders and traffic police. In total, 16 traffic police officers were interviewed and 105 traffic police officers were surveyed. In addition, 207 drunk driving offenders in detention facilities and 802 general motor vehicle drivers were surveyed. RESULTS: Traffic police resources including human resources and facilities such as breathalysers were reported as insufficient in both cities. There were problems reported in the process of law enforcement, and shortcomings in police knowledge of factors involved in drink/drunk driving and in the practice of conducting breath alcohol testing (BAT). Knowledge about legal BAC levels and how to keep under the legal limit was very low among general motor vehicle drivers and drunk driving offenders. Proportions with alcohol misuse problems in the two driver groups were high, especially among offenders. CONCLUSIONS: Recommendations to manage alcohol-related driving are proposed for the three groups of traffic police, general motor vehicle drivers and drunk driving offenders. In particular, traffic police resources need to be improved and further education provided to police on the general deterrence potential of BAT. There should be enhanced community education and publicity to improve knowledge of drink driving regulations and how to avoid breaking the law. Alcohol misuse problems should be addressed, particularly for drunk driving offenders. PMID- 26850754 TI - Delayed astrocytic contact with cerebral blood vessels in FGF-2 deficient mice does not compromise permeability properties at the developing blood-brain barrier. AB - The brain functions within a specialized environment tightly controlled by brain barrier mechanisms. Understanding the regulation of barrier formation is important for understanding brain development and may also lead to finding new ways to deliver pharmacotherapies to the brain; access of many potentially promising drugs is severely hindered by these barrier mechanisms. The cellular composition of the neurovascular unit of the blood-brain barrier proper and their effects on regulation of its function are beginning to be understood. One hallmark of the neurovascular unit in the adult is the astroglial foot processes that tightly surround cerebral blood vessels. However their role in barrier formation is still unclear. In this study we examined barrier function in newborn, juvenile and adult mice lacking fibroblast growth factor-2 (FGF-2), which has been shown to result in altered astroglial differentiation during development. We show that during development of FGF-2 deficient mice the astroglial contacts with cerebral blood vessels are delayed compared with wild type animals. However, this delay did not result in changes to the permeability properties of the blood brain barrier as assessed by exclusion of either small or larger sized molecules at this interface. In addition cerebral vessels were positive for tight-junction proteins and we observed no difference in the ultrastructure of the tight-junctions. The results indicate that the direct contact of astroglia processes to cerebral blood vessels is not necessary for either the formation of the tight-junctions or for basic permeability properties and function of the blood-brain barrier. (c) 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1201-1212, 2016. PMID- 26850755 TI - Using frozen section margin control technique to manage non-melanomatous skin lesions in high-risk sites. AB - BACKGROUND: In the UK, non-melanoma skin cancers (NMSCs) that are incompletely excised, recurrent or in sites high risk for incomplete excision are often offered Mohs micrographic surgery (MMS). Variations in waiting times and geographical access to MMS affect patient preference for other treatments. Our unit offers excision of such lesions under complete margin frozen section histological examination. METHODS: All NMSCs excised at our unit by complete margin frozen section histological analysis from 2010 to 2014 were retrospectively reviewed. The number of excisions required, complete excision rates and recurrences to date were analysed. RESULTS: Sixty-nine patients were treated using this technique with a total of 70 lesions excised. Approximately 71% of the excision margins were clear after primary excision, 27% at second excision and 1% at third excision. Patients had a mean follow-up of 12 months (range: 1-48) with no patients lost to follow-up and no recurrences reported to date. Ninety-eight percent of NMSC cases were completely excised and two cases were incompletely excised. CONCLUSION: We have found the rates of excision and recurrence of the high-risk NMSCs excised at our unit to be comparable to those reported with MMS. In addition, our data show that around 29% of patients would have had incomplete margins on primary resection, thus justifying the use of this technique in this group. We suggest that this technique is a safe and useful alternative to MMS in areas where waiting times or geographical patient preference may prohibit its use. PMID- 26850757 TI - Identification of a variant antigenic neutralizing epitope in hypervariable region 1 of avian leukosis virus subgroup J. AB - Avian leukosis virus subgroup J (ALV-J) is a hypervariable oncogenic retrovirus that causes great economic loss in poultry. Antigenic variations in the variable regions make the development of an effective vaccine a challenging task. In the present study, we identified a variant antigenic neutralizing epitope using reverse vaccinology methods. First, we predicted the B-cell epitopes in gp85 gene of ALV-J strains by DNAman and bioinformatics. Fourteen candidate epitopes were selected and linked in tandem with glycines or serines as a multi-epitope gene. The expressed protein of multi-epitope gene can induce high-titer antibody that can recognize nature ALV-J and neutralize the infectivity of ALV-J strains. Next, we identified a high effective epitope using eight overlapping fragments of gp85 gene reacting with mAb 2D5 and anti-multi-epitope sera. The identified epitope contained one of the predicted epitopes and localized in hyervariable region 1 (hr1), indicating a variant epitope. To better understand if the variants of the epitope have a good antigenicity, we synthesized four variants to react with mAb 2D5 and anti-ALV-J sera. The result showed that all variants could react with the two kinds of antibodies though they showed different antigenicity, while could not react with ALV-J negative sera. Thus, the variant antigenic neutralizing epitope was determined as 137-LRDFIA/E/TKWKS/GDDL/HLIRPYVNQS-158. The result shows a potential use of this variant epitopes as a novel multi-epitope vaccine against ALV-J in poultry. PMID- 26850756 TI - Place of influenza vaccination among children--United States, 2010-11 through 2013-14 influenza seasons. AB - BACKGROUND: Studies are published on settings adults receive influenza vaccination but few have reported on settings children are vaccinated and how this might be changing over time or vary by socio-demographics. METHODS: Data from the National Immunization Survey-Flu were analyzed to assess place of influenza vaccination among vaccinated children 6 months-17 years during the 2010 11, 2011-12, 2012-13, and 2013-14 influenza seasons. The percentage of children vaccinated at each place was calculated overall and by age, race/ethnicity, income, and Metropolitan Statistical Area (MSA). RESULTS: The places children received influenza vaccination varied little over four recent influenza seasons. From the 2010-11 through 2013-14 influenza seasons the percentage of vaccinated children receiving influenza vaccination at a doctor's office was 64.1%, 65.1%, 65.3%, and 65.3%, respectively with no differences from one season to the next. Likewise, for vaccination at clinics or health centers (17.8%, 17.5%, 17.0%. 18.0%), health departments (3.2%, 3.6%, 3.0%, 2.8%), and other non-medical places (1.6%, 1.4%, 1.2%, 1.1%), there were no differences from one season to the next. There were some differences for vaccinations at hospitals, pharmacies, and schools. There was considerable variability in the place of influenza vaccination by age, race/ethnicity, income, and MSA. Fewer Hispanic children were vaccinated at a doctor's office than black, white, and other or multiple race children and fewer black children and children of other or multiple races were vaccinated at a doctor's office than white children. More children at or below the poverty level were vaccinated at a clinic or health center than all of the other income groups. CONCLUSION: Most vaccinated children receive their influenza vaccination at a doctor's office. Place of vaccination changed little over four recent influenza seasons. Large variability in place of vaccination exists by age, race/ethnicity, income, and MSA. Monitoring place of vaccination can help shape future immunization programs. PMID- 26850759 TI - Successful introduction of an underutilized elderly pneumococcal vaccine in a national immunization program by integrating the pre-existing public health infrastructure. AB - BACKGROUND: Although pneumococcal vaccines had been recommended for the elderly population in South Korea for a considerable period of time, the coverage has been well below the optimal level. To increase the vaccination rate with integrating the pre-existing public health infrastructure and governmental funding, the Korean government introduced an elderly pneumococcal vaccination into the national immunization program with a 23-valent pneumococcal polysaccharide vaccine in May 2013. OBJECTIVE: The aim of this study was to assess the performance of the program in increasing the vaccine coverage rate and maintaining stable vaccine supply and safe vaccination during the 20 months of the program. METHODS: We qualitatively and quantitatively analyzed the process of introducing and the outcomes of the program in terms of the systematic organization, efficiency, and stability at the national level. RESULTS: A staggered introduction during the first year utilizing the public sector, with a target coverage of 60%, was implemented based on the public demand for an elderly pneumococcal vaccination, vaccine supply capacity, vaccine delivery capacity, safety, and sustainability. During the 20-month program period, the pneumococcal vaccine coverage rate among the population aged >=65 years increased from 5.0% to 57.3% without a noticeable vaccine shortage or safety issues. A web-based integrated immunization information system, which includes the immunization registry, vaccine supply chain management, and surveillance of adverse events following immunization, reduced programmatic errors and harmonized the overall performance of the program. CONCLUSION: Introduction of an elderly pneumococcal vaccination in the national immunization program based on strong government commitment, meticulous preparation, financial support, and the pre-existing public health infrastructure resulted in an efficient, stable, and sustainable increase in vaccination coverage. PMID- 26850758 TI - Antenatal immunisation intentions of expectant parents: Relationship to immunisation timeliness during infancy. AB - BACKGROUND: Most women decide about infant immunisation during pregnancy. However, we have limited knowledge of the immunisation intentions of their partners. We aimed to describe what pregnant women and their partners intended for their future child's immunisations, and to identify associations between parental intentions and the subsequent timeliness of infant immunisation. METHODS: We recruited a cohort of pregnant New Zealand (NZ) women expecting to deliver between April 2009 and March 2010. The cohort included 11% of births in NZ during the recruitment period and was generalisable to the national birth cohort. We completed antenatal interviews independently with mothers and partners. We determined immunisation receipt from the National Immunisation Register and defined timely immunisation as receiving all vaccines (scheduled at 6-weeks, 3- and 5-months) within 30 days of their due date. We described independent associations of immunisation intentions with timeliness using adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Of 6172 women, 5014 (81%) intended full immunisation, 245 (4%) partial immunisation, 140 (2%) no immunisation and 773 (13%) were undecided. Of 4152 partners, 2942 (71%) intended full immunisation, 208 (5%) partial immunisation, 83 (2%) no immunisation and 921 (22%) were undecided. Agreement between mothers and partners was moderate (Kappa=0.42). Timely immunisation occurred in 70% of infants. Independent of their partner's intentions, infants of pregnant women who decided upon full immunisation were more likely to be immunised on time (OR=7.65, 95% CI: 4.87-12.18). Independent of the future mother's intentions, infants of partners who had decided upon full immunisations were more likely to be immunised on time (OR=3.33, 95% CI: 2.29-4.84). CONCLUSIONS: During pregnancy, most future parents intend to fully immunise their child; however, more partners than mothers remain undecided about immunisation. Both future mothers' and future fathers' intentions are independently associated with the timeliness of their infant's immunisations. PMID- 26850760 TI - Adverse events following immunization in patients with primary immunodeficiencies. AB - BACKGROUND: Adverse events following immunization (AEFI) requires special consideration in patients with primary immunodeficiency diseases (PID) because they may represent a "red flag" for the initial diagnosis and may cause disease complications. Therefore, the definition of appropriate vaccination schemes is a major issue in PID. The aim of this study is to describe the AEFI in a cohort of PID patients. METHODS: Medical records from 379 PID patients were included. AEFI severity was classified according to the WHO 1999 guidelines. Causality was assessed using the Clinical Immunization Safety Assessment (CISA) 2009 criteria. RESULTS: Evidence of AEFI was found in 26 medical records and represented a total of 29 reactions. Most of the AEFI were observed in patients with idiopathic hypogammaglobulinemia (IHG), chronic granulomatous disease (CGD) and severe combined immunodeficiency (SCID), representing 10, 4 and 4 cases, respectively. A total of 21 reactions were associated with replicative vaccines, 7 of which were serious cases related to Bacille Calmette-Guerin (BCG). BCG was also the vaccine more often associated with definitive AEFI in PID. In addition to BCG-related complications, seizures were the most serious AEFI among PID patients. CONCLUSIONS: Our study included a large cohort of PID patients and confirmed an increased risk of serious AEFI in these populations. The design and implementation of neonatal screening strategies for the early detection of congenital lymphopenias and other PID are urgently needed to avoid serious complications of the BCG vaccine usually applied immediately after birth. Our findings also support the use of the acellular pertussis vaccine to minimize the appearance of seizures in PID patients vaccinated with diphtheria, pertussis and tetanus (DPT). PMID- 26850761 TI - Response to stimulus relations by a dog (Canis lupus familiaris). AB - A malamute-husky mixed-breed dog was trained to distinguish one object that differed from three others that were identical to each other. The dog progressed rapidly after an effective shaping procedure, requiring 37 training sessions to master 20 such problems to a criterion of 90 %. The dog subsequently scored 80 % correct on the first trials with new problems that required a reversal of previously correct choices. The dog then scored 70 % correct on his first trials with 20 new problems composed of entirely new objects. Both performances are far above chance. Consequently, we conclude that choosing the odd or least numerous object in a group is within the capacity of the domestic dog. PMID- 26850763 TI - Author's reply to the letter of Doll et al. PMID- 26850762 TI - Genomic Information may Inhibit Weight-Related Behavior Change Inclinations Among Individuals in a Fear State. AB - BACKGROUND: As evidence mounts regarding associations between genetics and body weight, it is essential to understand how to communicate this information, and factors like emotion that could moderate the effectiveness of messages. PURPOSE: We assessed influences of emotion on reactions to weight-related genomic information in a virtual clinical setting. METHODS: An online representative US sample of overweight women was randomized to receive an emotion induction (anger, fear, or neutral) paired with information about genomic or behavioral influences on weight in an interaction with a virtual doctor. RESULTS: Receiving genomic information led to reduced attributions of lifestyle causes for weight and behavioral intentions, but only among individuals in a fear state. CONCLUSIONS: The current study is among the first to reinforce the concern that discussing genomic underpinnings of overweight could undercut health behavior, and highlights the importance of identifying factors like emotion that influence interpretation of genomic information. Clinicaltrials.gov NCT01888913. PMID- 26850764 TI - Quality of patient information online for rectal prolapse. PMID- 26850765 TI - Caspofungin-induced in-vitro post-antifungal effect and its impact on adhesion related traits of oral Candida dubliniensis and Candida albicans isolates. AB - Adhesion to buccal epithelial cells (BEC) and denture acrylic surfaces (DAS), germ tube (GT) formation and cell surface hydrophobicity (CSH) are all virulence traits involved in the pathogenicity of Candida. Post-antifungal effect (PAFE) also have a bearing on pathogenicity and virulence of Candida. Candida dubliniensis is associated with oral and systemic candidosis, which can be managed with caspofungin. There is no published information on caspofungin induced PAFE and its impact on adhesion traits of C. dubliniensis isolates. Thus, the purpose of this investigation was to determine the in vitro duration of PAFE on 20 C. dubliniensis isolates following transient exposure to caspofungin. Furthermore the impacts of caspofungin-induced PAFE on adhesion to BEC and DAS, GT formation and CSH of these isolates were also determined. After establishing the minimum inhibitory concentration (MIC) of caspofungin, C. dubliniensis isolates were exposed to sub-lethal concentrations (*3 MIC) of caspofungin for 1 hr. Thereafter the duration of PAFE, adhesion to BEC and DAS, GT formation and CSH were determined by previously described in-vitro assays. MIC (MUg/mL) of C. dubliniensis isolates to caspofungin ranged from 0.004 to 0.19. Caspofungin induced mean PAFE on C. dubliniensis isolates was 2.17 hr. Exposure to caspofungin suppressed the ability of C. dubliniensis isolates to adhere to BEC and DAS, form GT and CSH by 69.97%, 71.95%, 90.06% and 32.29% (P < 0.001 for all), respectively. Thus, transient exposure of C. dubliniensis isolates to caspofungin produces an antifungal effect not only by suppressing its growth but also by altering its adhesion traits. PMID- 26850766 TI - Alabama pays town's residents to undergo TB testing. PMID- 26850767 TI - [Remarks on the establishment of intracranial tuberculosis imaging classification]. PMID- 26850768 TI - [The advantage of delayed-phase multi-slice Computed Tomography for the diagnosis of intracranial tuberculosis]. AB - OBJECTIVE: To study the advantages of delayed phase scan at 5 minutes using multi slice Computed Tomography (CT) for the diagnosis of intracranial tuberculosis. METHODS: Conventional non-contrast and dual-phase contrast enhancement were performed using 16-slice spiral CT for brain scanning. Arterial phase was performed 25 seconds after the injection of contrast agent, and the delayed phase was performed at 5 minutes. Then the ability of two phase images in intracranial tuberculosis displaying was evaluated. RESULTS: A total of 526 lesions in 30 patients were found. Delayed phase scan was superior to arterial phase in the ability of displaying the thickening of meninges, either basal cistern, pia mater or ependymal (P<0.01). The demonstration of lesion size and margins of tuberculoma was also better in delayed phase scan (P<0.01). The delayed phase scan was significantly better in distinguishing lesions and adjacent vascular sections in the sulcus (P<0.01). CONCLUSION: The delayed phase scan has obvious advantages in the display of intracranial tuberculosis. PMID- 26850769 TI - [MR image analysis of 147 cases of meningeal tuberculosis]. AB - OBJECTIVE: To investigate the MRI features of meningeal tuberculosis. METHODS: The MR images of meningeal tuberculosis were retrospectively analyzed in 147 patients who were clinically diagnosed from 2009 to 2014 years in our hospital, including 77 males, and 70 females. Their age ranged from 14 to 70 years, and the average age was(32 +/- 13)years. All cases underwent MR plain scan and enhancement scan, and 26 cases underwent 3D TOF sequence and MRA vascular reconstruction. The characteristics of the morphological change, MR signal of meningeal lesions and the secondary changes were investigated for 56 cases of meningeal carcinomatosis due to lung cancer, including 29 males and 27 females. Their age ranged from 36 to 78 years old, and the average age was (58 +/- 11)years. The MR imaging characteristics of meningeal lesions were compared with those of meningeal tuberculosis. Chi-square test and logistic regression analysis were used for count data analysis, and t-test was used for measurement data. P<0.05 was regarded as statistically significant. RESULTS: Among 147 cases of meningeal tuberculosis, 146 (99.32%) had involvement of the cerebral pia mater, 104 of the basal cistern, and 108 of the cistern of lateral fissure pools. Lesions located in fissura longitudinalis cerebri pool, convexity of brain and cerebellar back were found in 46, 35 and 17 cases, respectively. MRI findings in plain scan were normal in 11 patients, and abnormal in 136 cases. Thickening meningeal lesions with different degrees were shown in the abnormal cases, with irregular or nodular slightly low signal intensity in T2WI in 77 cases. The meningeal lesions of all cases had homogeneous or inhomogeneous enhancement in enhanced scanning. There were 85 cases with meningeal nodules, including nodules with scattered distribution in 23 cases, and cluster distribution in 62 cases. The number of nodules was up to 1 105, including 452 nodules with homogeneous enhancement, and 653 nodules with ring enhancement. Most nodules of cluster distribution showed ring enhancement or separate enhancement. Secondary changes included hydrocephalus in 94 cases, anterior cerebral artery involvement in 17 cases, middle cerebral artery involvement in 58 cases, posterior cerebral artery involvement in 9 cases, 42 cases complicated with cerebral infarction and optic nerve involvement in 49 cases. Comparison of MR manifestations of meningeal tuberculosis and meningeal metastasis showed that, the location, type of meningeal involvement, edge of lesions, relative position of lesions and meninges, distribution of nodules were significantly different(P<0.05), except arachnoid lesions (P=0.066). CONCLUSION: The MRI characteristics of meningeal tuberculosis were thickening of cerebral basilar cistern meninges. These signs were valuable for MRI diagnosis of meningeal tuberculosis, including cases complicated with meningeal nodules of cluster distribution. The nodules were of low signal on T2WI, with ring enhancement or separate enhancement, with secondary hydrocephalus, cerebral vasculitis in anterior circulation, and brain infarction. The result also showed that contrast-enhanced MRI was valuable for diagnosis of meningeal tuberculosis as well. PMID- 26850771 TI - [Analysis on 23 cases of spinal meningeal tuberculosis by magnetic resonance imaging]. AB - OBJECTIVE: To explore the imaging features of spinal cord and spinal meningeal tuberculosis by magnetic resonance (MR). METHODS: We analyzed retrospectively the features of MRI in 23 patients with spinal cord and spinal meningeal tuberculosis compared to 25 patients with spinal cord meningeal metastatic carcinoma. All patients were admitted in our hospital from Jun. 2011 to Oct. 2014. There were 12 males and 11 females with a median age of 26 (range 16-50) years in the spinal cord meningeal tuberculosis group, and 18 males and 7 females with a median age 56 (range 44-78) years in the spinal cord meningeal metastatic carcinoma group. All patients underwent MR plain and contrast-enhanced scanning. The enumeration data were compared with the chi2 test and the measurement data were compared with t test. The difference was considered statistically significant when the P value was <0.05. RESULTS: Of the 23 cases, 16 were spinal meningeal tuberculosis and 7 were spinal cord tuberculosis. The MR imaging features were as follows: (1) Spinal meningeal tuberculosis: Irregular and linear strip and hummocky thickening (thickness <5 mm) of the meninges (dura, arachnoid and pia mater), with the average length of involvement of 7 vertebral segments. Enhancement was present in all cases by contrast-enhanced scanning, including clustering or moniliform enhancement in 5 cases. Subarachnoid irregular stenosis was seen in all cases, partial occlusion in 5, abnormal heterogeneous signal in 20, rough cerebrospinal fluid (CSF)-spinal interface in 10, and formation of secondary arachnoid cyst in 15. (2) Spinal cord meningeal tuberculosis: of the 7 cases, 4 showed ring enhancement and 3 showed small plaque with heterogeneous enhancement. (3) There were 20 cases of meningeal metastatic carcinoma and 5 cases of meningeal metastatic carcinoma with spinal cord metastasis. Nodular thickening was present in 8 cases, plaque thickening in 10, and nodular and plaque thickening in 7. Continuous thickening involving 3 vertebral bodies was seen in 19 cases. Multiple localized thickening was present in 6 cases, with obvious enhancement in the meninges and heterogeneous enhancement in the spinal cord. CONCLUSIONS: The MR imaging features of spinal cord meningeal tuberculosis include continuous meningeal thickening, secondary arachnoid cyst, rough and moniliform CSF-spinal cord interface. Diagnosis and differential diagnosis can be made based on these features combined with clinical data and disease history. PMID- 26850770 TI - [MRI features of cerebral parenchymal tuberculosis and the dynamic evolution during antituberculous treatment]. AB - OBJECTIVE: To investigate the MRI features, classification and the evolution of cerebral parenchymal tuberculosis (TB) during anti-tuberculosis treatment. METHODS: A total of 134 patients with cerebral parenchymal TB registered in our hospital from Sep. 2010 to Aug. 2010 were studied retrospectively. There were 68 males and 66 females, aged 14 to 77 years. The MRI characteristics of these patients were analyzed after T1WI, T2WI, DWI and enhanced scan.The millet, small and large nodules were named by the lesion diameter of less than 0.3 cm, 0.3 to 1.0 cm and lager than 1.0 cm in brain parenchymal TB, respectively, and accordingly the cerebral parenchymal TB cases were divided into millet nodule type, small nodule type, large nodule type and mixed nodule type with at least 2 of 3 nodule sizes. According to the enhanced scanning patterns and signal characteristics, the cases were divided into hyperplastic nodule, tuberculoma type, abscess type and mixed type. Serial follow-up MRI scans were performed in 76 patients during their anti-tuberculosis treatment.Data on lesions of different size were analyzed by Chi-square test and the follow-up results were analyzed by single-factor logistic regression. RESULTS: Of all the 134 patients, the lesions were commonly found in the cerebral hemisphere and cerebellar hemisphere, often multiple in different locations. Three patterns of homogeneous enhancement, ring enhancement, and variegated enhancement were found in the 134 patients after the enhanced scan, of which 2 or more patterns co-existed in 72 cases. There were 124 cases with millet nodules, of which 116 were homogeneous enhancement and 32 were heterogeneous enhancement (including ring enhancement and variegated enhancement). Ninety cases were found to have small nodules, of which 34 were homogeneous enhancement and 69 were heterogeneous enhancement. Sixty cases were found to have large nodules, of which 1 was of homogeneous enhancement and 16 were of heterogeneous enhancement. The case number of the homogeneous enhancement and heterogeneous enhancement was significantly different for the 3 different sized nodules, respectively (P<0.05). Homogeneous enhancement was seen commonly in millet nodules, while heterogeneous enhancement in small nodules especially large nodules. In contrast to small nodule type (8 cases) and large nodule type (1 case), millet nodule type (68 cases) and mixed nodule type (57 cases) were predominant. The hyperplastic nodule type (64 cases) and mixed cerebral tuberculosis (60 cases) were predominant in contrast to tuberculoma type (9 cases) and abscess type (1 case) in the 134 patients. The cases with lesion diameter more than 0.5 cm mostly showed tuberculoma. The disappearance rates were 23 (30.3%) among 76 patients with serial MRI follow-up scans. The disappearance rate of hyperplastic nodule type (17/37) was significantly higher than that of the non-hyperplastic nodule type (including tuberculoma and mixed type) (6/39) (P=0.004). The disappearance rate of millet nodule type (15/38) was significantly higher than that of the non-millet nodule type (8/38) (P=0.02). Single-factor logistic regression analysis showed that, the results of the follow-up only related to 2 classifications (P<0.05). Fourteen patients were found to have enlarged lesions or newly appeared lesion during anti-tuberculosis treatment, of which 3 were refractory. CONCLUSIONS: Cerebral parenchymal TB showed certain MRI characteristics. Homogeneous enhancement, ring enhancement, and variegated enhancement. About half of the patients had more than 2 enhancement patterns. Homogeneous enhancement and heterogeneous enhancement were commonly seen in millet nodules and small nodules especially large nodules, respectively. According to the classification of lesion size, millet nodule type and mixed nodule type were predominant. According to the characteristics of the lesion enhancement pattern and signal characteristics, hyperplastic nodule type and mixed type were predominant. This classification would help to guide the treatment of cerebral parenchymal TB. The treatment effect of hyperplastic nodule type was better than non-hyperplastic nodule type, and millet nodule type was better than non-millet nodule types. PMID- 26850772 TI - [Clinical and genetic study on familial idiopathic pulmonary fibrosis in a Chinese family]. AB - OBJECTIVE: To identify the manifestations and pathogenesis of idiopathic pulmonary fibrosis (IPF) after studying the clinical features of familial idiopathic pulmonary fibrosis (FIPF) and detecting relevant genes. METHODS: Seven persons with FIPF from one family of Han nationality in northern China, which had FIPF patients in three consecutive generations, were included in this study. The incidence age of the 7 subjects (4 males and 3 females) ranged from 30 to 57 years. The propositus was II-4, while the first person attacked by FIPF was I-1. Five patients (2 males, 3 females) in the second generation and one case in the third generation were found at the time of this study. The genetic characteristics of FIPF in this study were complied with the pattern of autosomal dominant inheritance. Imaging examinations and pulmonary function tests were conducted to confirm the diagnosis of pulmonary fibrosis. Meanwhile, personal information and clinical data such as imaging examinations and pathological tests were acquired; clinical features and manifestations were analyzed and compared; and pathological tests and gene detection were performed. RESULTS: The average survival time was 3 years, and poor response to glucocorticoid treatment was observed. Three patients had detailed clinical information, whose interstitial pneumonia related immunologic tests were negative. Concerning pulmonary function, three patients had significant decrease of diffusion function and obvious restrictive ventilatory disorder, with DLCO value as 50%, 23% and 46%, respectively. Among the 3 patients with complete imaging data, 1 was considered as UIP, while 2 as NSIP. The 3 subjects who had different imaging findings all responded poorly to glucocorticoid treatment, and two of them died. Genetic test for TERT, TERC and SFTPC in peripheral blood and autopsy were performed for II-4 but all were negative. CONCLUSIONS: The average death age of family members with FIPF was 50.2 years. The patients presented various imaging features and pathological findings. Glucocorticoid treatment may be ineffective, even for persons diagnosed as NSIP by lung biopsy. PMID- 26850773 TI - [The value of bronchoscopy in the diagnosis of sarcoidosis]. AB - OBJECTIVE: To evaluate the role of bronchoscopy in the diagnosis of sarcoidosis. METHODS: A retrospective analysis was conducted for 200 patients who were diagnosed to have sarcoidosis and underwent bronchoscopy from June 2009 to June 2014 in Peking Union Medical College Hospital. The diagnostic value of different bronchoscopic procedures was analyzed. RESULTS: Of the 200 patients, 145 were finally confirmed to have sarcoidosis by pathology through bronchoscopic sampling techniques. The diagnostic yields of endobronchial biopsy (EBB), transbronchial lung biopsy (TBLB), and EBUS-TBNA were 71.14%, 46.77%, 46.80%, respectively. The yields among the 3 techniques were statistically different. In those with mucosal lesions, the yield of EBB was 80.80%, while that of the combination of EBB, TBLB and EBUS-TBNA was 83.3%, the difference being not significant. In those without mucosal lesions, the yields of EBB, and the combination of EBB, TBLB and EBUS TBNA were 20.8% and 48.0% respectively, with significant difference(chi(2)=4.463, P=0.035). CONCLUSIONS: EBB is a preferred approach for the diagnosis of sarcoidosis with endobronchial abnormalities, while for cases without mucosal lesions, combined TBLB, EBUS-TBNA and bronchoalveolar lavage can improve the diagnostic yield. PMID- 26850774 TI - [Validation of the advanced event detection in patients with sleep apnea hypopnea syndrome using auto-CPAP treatment]. AB - OBJECTIVE: To validate the use of the event detection capabilities in an auto CPAP system used by patients with sleep apnea hypopnea syndrome (SAHS). METHODS: A total of 28 subjects with SAHS were recruited in the study. All the underwent tests of polysomnography (PSG) before and during treatment by an-auto-CPAP system with advanced event detection (AED) in the sleep lab. Apnea-hypopnea index (AHI), apnea index (AI) and hypopnea index (HI) by PSG and PAP machine were compared. RESULTS: The mean AHI derived from PSG and AED was (6.1 +/- 5.6) and (7.1 +/- 5.3) times/h (P>0.05), AI was (5.4 +/- 5.4) and (4.6 +/- 4.2) times/h (P>0.05), HI was (0.77 +/- 1.07) and (2.54 +/- 1.98) times/h (P<0.05). The Spearman correlation coefficient of AHI was 0.698 (P<0.05), AI was 0.767 (P<0.05), HI was 0.141 (P>0.05). Bland-Altman plot also showed a high agreement between AHI derived from PSG and AHI derived from AED. CONCLUSION: AED showed a high agreement with PSG in the detection of AHI and AI, but not in HI. This technique may be helpful to monitor the efficacy of PAP treatment at home for long-term follow-up. PMID- 26850775 TI - [Effect of oxygen tubing connection site, changes of the inspiratory positive airway pressure and tidal volume on inspired oxygen concentration during noninvasive positive pressure ventilation]. AB - OBJECTIVE: We evaluated the effects of administering oxygen through nasal catheter inside the mask or through the mask on inspired oxygen concentration in order to find better ways of administering oxygen to improve the inspired oxygen concentration in non-invasive positive pressure ventilation (NPPV). METHODS: A human face model was used to simulate the human face, and the model of the double lumen endotracheal tube was used to simulate the bilateral nasal cavity and trachea, and then a model was constructed to allow simulated NPPV. The changes of FIO2were measured in different pressure (constant tidal volume) and different tidal volume (constant pressure) conditions under the way of administering oxygen through nasal catheter inside the mask or through the mask. The effects on FIO2were measured in different pressure (constant tidal volume) and different tidal volume (constant pressure) conditions under same way of administering oxygen. RESULTS: The FIO2was (35.4 +/- 1.7)% when oxygen was administered through the mask, but a higher FIO2was achieved with the oxygen injected into the mask [(52.4 +/- 2.1)%, and oxygen flow of 5 L/min, P<0.05]. The oxygen concentration declined with the increase of inspiratory positive airway pressure (IPAP) on the condition of administering oxygen through the mask on constant tidal volume. The FIO2at IPAP 16 cmH2O (1 cmH2O=0.098 kPa) was higher than that at IPAP 8 cmH2O, and the FIO2at IPAP 20 cmH2O was higher than those at IPAP 8 cmH2O and 12 cmH2O, P<0.05. The oxygen concentration increased with the tidal volume increase on the condition of administering oxygen through the mask on constant IPAP. The changes of tidal volume and IPAP had no effects on FIO2on the condition of administering oxygen through nasal catheter inside the mask. CONCLUSIONS: Administering oxygen through nasal catheter inside the mask during NPPV can increase FIO2and conserve oxygen. This study provides theoretical basis for the development of newer masks. PMID- 26850776 TI - [Tanshinone II A for pulmonary hypertension: mechanisms of action]. PMID- 26850777 TI - [Advances in acute pulmonary vascular reaction test for patients with pulmonary hypertension]. PMID- 26850778 TI - Abdominal tuberculosis manifested as tuberculosis of the urachal sinus in an adolescent and the role of laparoscopy in the management: a rare case report. AB - BACKGROUND: Abdominal tuberculosis (TB) is an uncommon affliction in adolescence. It is usually associated with pulmonary tuberculosis. The disease is caused by lymphohaematogenous spread after primary infection in the lung or ingestion of infected sputum and has a typically protean and nonspecific presentation. The occurrence of TB in an urachal remnant is probably from the contiguous spread of an abdominal focus or mesenteric lymph node. Urachal TB is a rare entity, with only two reported cases in the literature. We report here a case of clinically silent pulmonary and abdominal TB that manifested in the infection of an urachal sinus and highlight the role of laparoscopy in its diagnosis and treatment. CASE PRESENTATION: A 14-year-old boy presented to our institution with peri-umbilical swelling and purulent discharge from his umbilicus for 2 weeks duration. There were no radiological, microbiological or clinical evidences of TB in the initial presentation, though he had close social contact with someone who had TB. A computed tomography scan of the abdomen confirmed the diagnosis of an urachal abscess. An incision and drainage procedure was performed followed by a course of antibiotics. A scheduled laparoscopic approach later showed that the peritoneum and serosal surface of the small and large intestines were studded with nodules of variable sizes, in addition to the urachal sinus. The histology of the resected tissues (urachal sinus and nodules) was consistent of TB infection. He recovered fully after completing 6 months of anti-tuberculous therapy. CONCLUSION: This report highlights a rare case of TB urachal abscess in an adolescent boy, the difficulties in the diagnosis of abdominal tuberculosis, the need to consider TB as a cause of urachal infection in endemic areas and the use of laparoscopy in both diagnosis and treatment. PMID- 26850779 TI - Are primary renal cell carcinoma and metastases of renal cell carcinoma the same cancer? AB - Metastasis is a process consisting of cells spreading from the primary site of the cancer to distant parts of the body. Our understanding of this spread is limited and molecular mechanisms causing particular characteristics of metastasis are still unknown. There is some evidence that primary renal cell carcinoma (RCC) and metastases of RCC exhibit molecular differences that may effect on the biological characteristics of the tumor. Some authors have detected differences in clear cell and nonclear cell component between these 2 groups of tumors. Investigators have also determined that primary RCC and metastases of RCC diverge in their range of renal-specific markers and other protein expression, gene expression pattern, and microRNA expression. There are also certain proteins that are variously expressed in primary RCCs and their metastases and have effect on clinical outcome, e.g., endothelin receptor type B, phos-S6, and CD44. However, further studies are needed on large cohorts of patients to identify differences representing promising targets for prognostic purposes predicting disease-free survival and the metastatic burden of a patient as well as their suitability as potential therapeutic targets. To sum up, in this review we have attempted to summarize studies connected with differences between primary RCC and its metastases and their influence on the biological characteristics of renal cancer. PMID- 26850780 TI - Timing of blood transfusion and not ABO blood type is associated with survival in patients treated with radical cystectomy for nonmetastatic bladder cancer: Results from a single high-volume institution. AB - INTRODUCTION AND OBJECTIVES: Perioperative transfusions have been recently associated to poor outcomes as an indirect consequence of immune-hematological changes related to transfusion itself and blood type. We tested the role of blood transfusion on cancer-specific mortality (CSM) and overall mortality (OM), considering the effect of ABO system, Rh factor, and timing of transfusions. MATERIALS AND METHODS: The study focused on 728 patients with bladder cancer treated with radical cystectomy at a single tertiary care referral center between January 1995 and August 2013 with complete ABO blood type information. Kaplan Meier analysis was used to assess the effect of transfusions, stratified according to ABO type and Rh factor, on CSM and OM. The same endpoints were tested in Cox regression models, after adjusting for all available confounders. RESULTS: A total of 341 (46.8%), 277 (38.0%), 83 (11.4%), and 27 (3.7%) patients had blood type O, A, B and AB, respectively. Overall, 630 (86.5%) and 98 (13.5%) patients were Rh-and Rh+, respectively. At a median follow-up time of 65 months, 225 (30.9%) and 282 (38.7%) patients recorded CSM and OM, respectively. At univariable analyses, ABO blood type and Rh status were not associated to either CSM or OM (all P>0.2). Similar results were observed when ABO blood type and Rh factor were tested in multivariable models (all P>0.3). Conversely, Charlson score, preoperative hemoglobin, number of nodes removed, pathological T stage, and number of positive nodes were associated to both CSM and OM (all P<0.05). Interestingly, intraoperative transfusion (all P<0.03) but not the administration of blood units in the postoperative period (P>0.05) was associated with an increase of CSM and OM. CONCLUSIONS: Although ABO type or Rh factor or both were associated with several adverse outcomes in many cancers, we were not able to confirm this association in bladder cancer. Based on our results, the effect of transfusion on survival is independent by ABO type but is associated to the timing of blood supply administration. PMID- 26850781 TI - Abiraterone acetate post-docetaxel for metastatic castration-resistant prostate cancer in the Belgian compassionate use program. AB - BACKGROUND: Abiraterone acetate (AA) is licensed for treating metastatic castration-resistant prostate cancer (mCRPC). Real-world data on oncological outcome after AA are scarce. The current study assesses efficacy and safety of AA in mCRPC patients previously treated with docetaxel who started treatment during the Belgian compassionate use program (January 2011-July 2012). PATIENTS AND METHODS: Records from 368 patients with mCRPC from 23 different Belgian hospitals who started AA 1000mg per day with 10mg prednisone or equivalent were retrospectively reviewed (September 2013-December 2014). Prostate-specific antigen (PSA) response (decrease>=50%), time to PSA progression (increase>50% over PSA nadir in case of PSA response/>25% in absence of PSA response), time to radiographic progression (on bone scans or for soft tissue lesions using Response Evaluation Criteria In Solid Tumors 1.1), overall survival and adverse event rate (Common Terminology Criteria for Adverse Events v4.03) were analyzed. Kaplan Meier statistics were applied. RESULTS: Overall, 92 patients (25%) had an Eastern Cooperative Oncology Group performance status>=2. Median age was 73 years, median PSA was 103ng/dl. PSA response was observed in 131 patients (37.4%). Median time to PSA and radiographic progression was 4.1 months (95% CI: 3.6-4.6) and 5.8 months (5.3-6.4), respectively. Median overall survival was 15.1 months (13.6 16.6). Most common grade 3 to 4 adverse events were anemia (13.9%), hypokalemia (7.3%), fatigue (6.8%), and pain (6.3%). Median duration of AA treatment was 5.3 months (interquartile range: 2.8-10.3). The main study limitation is its retrospective design. CONCLUSIONS: These real-world data on post-docetaxel AA efficacy are in line with the COU-AA-301 trial. Importantly, incidence of severe anemia and hypokalemia is up to 50% higher than reported in previous studies. PMID- 26850782 TI - Benefits of aerobic or resistance training during pregnancy on maternal health and perinatal outcomes: A systematic review. AB - OBJECTIVE: To understand what evidence exists with regard to maternal and offspring benefits of aerobic and/or resistance training during pregnancy. METHODS: Systematic review of RCTs (published until May 2015) with healthy pregnant women and focusing on the benefits of exercise interventions on maternal health or perinatal outcomes. Studies were ranked as high/low quality, and a level of evidence was established according to the number of high-quality studies and consistency of the results. RESULTS: 61 RCTs were analyzed. The evidence for a benefit of combined exercise [aerobic+resistance (muscle strength)] interventions on maternal cardiorespiratory fitness and prevention of urinary incontinence was strong. A weak or insufficient level of evidence was found for the rest of interventions and outcomes CONCLUSION: The exercise modality that seems to induce a more favorable effect on maternal health is the combination of aerobic and resistance exercises during pregnancy. PMID- 26850783 TI - Effect of cisplatin containing liposomes formulated by unsaturated chain containing lipids on gynecological tumor cells. AB - Gynecological tumors are major therapeutic areas of platinum-based anticancer drugs. Here, we report the characterization and in vitro biological assays of cisplatin-containing Egg L-alpha-phosphatidylcholine liposomes with different amounts of cholesterol. Dynamic light scattering estimated sizes of all obtained liposomes in the 100 nm range that are suitable for in vivo use. On the basis of these data and of the drug loading values, the best formulation has been selected. Stability and drug release properties of platinum-containing liposomes have been verified in serum. The growth inhibitory effects of both liposomal and free drug in a panel of ovarian and breast human cancer cell lines, characterized by a different drug sensitivity, give comparable or better results with respect to free cisplatin drug. PMID- 26850784 TI - The association between influenza infection, vaccination, and atrial fibrillation: A nationwide case-control study. AB - BACKGROUND: Influenza infection could activate systemic inflammatory responses and increase the sympathetic tone that plays an important role in the pathogenesis of atrial fibrillation (AF). OBJECTIVES: The goal of the present study was to investigate whether influenza infection was a risk factor for AF. We also aimed to study whether influenza vaccination could decrease the risk of AF. METHODS: From 2000 to 2010, a total of 11,374 patients with newly diagnosed AF were identified from the Taiwan National Health Insurance Research Database. On the same date of enrollment, 4 control patients (without AF) with matched age and sex were selected to be the control group for each study patient. The relationship between AF and influenza infection or vaccination 1 year before the enrollment was analyzed. RESULTS: Compared with patients without influenza infection or vaccination (reference group; n = 38,353), patients with influenza infection without vaccination (n = 1369) were associated with a significantly higher risk of AF with an odds ratio of 1.182 (P = .032) after adjustment for baseline differences. The risk of AF was lower in patients receiving influenza vaccination without influenza infection (n = 16,452) with an odds ratio of 0.881 (P < .001). In patients who have received influenza vaccination and experienced influenza infection (n = 696), the risk of AF was similar to that in the reference group (odds ratio 1.136; P = .214). The lower risk of AF with vaccination was consistently observed in subgroup analyses. CONCLUSION: Influenza infection was significantly associated with the development of AF, with an 18% increase in the risk, which could be reduced through influenza vaccination. PMID- 26850785 TI - The flu and atrial fibrillation: Nothing to sneeze at. PMID- 26850787 TI - Treatment-resistant panic disorder: clinical significance, concept and management. AB - Panic disorder is commonly prevalent in the population, but the treatment response for panic disorder in clinical practice is much less effective than that in our imagination. Increasing evidence suggested existence of a chronic or remitting-relapsing clinical course in panic disorder. In this systematic review, we re-examine the definition of treatment-resistant panic disorder, and present the potential risk factors related to the treatment resistance, including the characteristics of panic disorder, other psychiatric and physical comorbidities, and psychosocial stresses. Furthermore, we summarize the potential pathophysiologies, such as genetic susceptibility, altered brain functioning, brain-derived neurotrophic factor, and long-term inflammation, to explain the treatment resistance. Finally, we conclude the current therapeutic strategies for treating treatment-resistant panic disorder from pharmacological and non pharmacological views. PMID- 26850788 TI - Carbonic anhydrase inhibition and cytotoxicity studies of Mannich base derivatives of thymol. AB - Mannich bases of thymol were synthesized. The aminomethylation reaction was realised in the ortho position of the phenol for compounds 2 (dipropylamine), 3 (benzylamine), and 4 (dibenzylamine) while it was from para position for 1 (dimethylamine), 5 (piperidine), 6 (morpholine) and 7 (N-methylpiperazine). The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory effects of the compounds were asssessed against hCA I and hCA II. All compounds moderately inhibited hCA I and hCA II. The cytotoxicity of the compounds against four human oral squamous cell carcinoma cell lines were compared those against three normal oral cells. Tumor specificity values were about 2 or slightly more for the compounds 2, 3, 4, 5 and 6. Compound 2 showed cytostatic activity against OSCC cell lines at 16 to 32-fold lower concentrations as compared with normal cells. This suggests that compound 2 can be considered as cytotoxicity enhancing drug candidate for further investigations. PMID- 26850786 TI - Genetic and Dietary Regulation of Glyburide Efflux by the Human Placental Breast Cancer Resistance Protein Transporter. AB - Glyburide is frequently used to treat gestational diabetes owing to its low fetal accumulation resulting from placental efflux by the breast cancer resistance protein (BCRP)/ABCG2 transporter. Here we sought to determine how exposure to the dietary phytoestrogen genistein and expression of a loss-of-function polymorphism in the ABCG2 gene (C421A) impacted the transport of glyburide by BCRP using stably transfected human embryonic kidney 293 (HEK) cells, human placental choriocarcinoma BeWo cells, and human placental explants. Genistein competitively inhibited the BCRP-mediated transport of (3)H-glyburide in both wild-type (WT) and C421A-BCRP HEK-expressing cells, with greater accumulation of (3)H-glyburide in cells expressing the C421A variant. In BeWo cells, exposure to genistein for 60 minutes increased the accumulation of (3)H-glyburide 30%-70% at concentrations relevant to dietary exposure (IC50 ~180 nM). Continuous exposure of BeWo cells to genistein for 48 hours reduced the expression of BCRP mRNA and protein by up to 40%, which impaired BCRP transport activity. Pharmacologic antagonism of the estrogen receptor attenuated the genistein-mediated downregulation of BCRP expression, suggesting that phytoestrogens may reduce BCRP levels through this hormone receptor pathway in BeWo cells. Interestingly, genistein treatment for 48 hours did not alter BCRP protein expression in explants dissected from healthy term placentas. These data suggest that whereas genistein can act as a competitive inhibitor of BCRP-mediated transport, its ability to downregulate placental BCRP expression may only occur in choriocarcinoma cells. Overall, this research provides important mechanistic data regarding how the environment (dietary genistein) and a frequent genetic variant (ABCG2, C421A) may alter the maternal-fetal disposition of glyburide. PMID- 26850789 TI - Impaired physical function following pediatric LT. AB - The purpose of this article is to investigate the spectrum of physical function of pediatric liver transplantation (LT) recipients 12-24 months after LT. Review data were collected through the functional outcomes group, an ancillary study of the Studies of Pediatric Liver Transplantation registry. Patients were eligible if they had survived LT by 12-24 months. Children >= 8 years and parents completed the Pediatric Quality of Life InventoryTM 4.0 generic core scales, which includes 8 questions assessing physical function. Scores were compared to a matched healthy child population (n = 1658) and between survivors with optimal versus nonoptimal health. A total of 263 patients were included. Median age at transplant and survey was 4.8 years (interquartile range [IQR], 1.3-11.4 years) and 5.9 years (IQR, 2.6-13.1 years), respectively. The mean physical functioning score on child and parent reports were 81.2 +/- 17.3 and 77.1 +/- 23.7, respectively. Compared to a matched healthy population, transplant survivors and their parents reported lower physical function scores (P < 0.001); 32.9% of patients and 35.0% of parents reported a physical function score <75, which is > 1 standard deviation below the mean of a healthy population. Physical functioning scores were significantly higher in survivors with optimal health than those with nonoptimal health (P < 0.01). There was a significant relationship between emotional functioning and physical functioning scores for LT recipients (r = 0.69; P < 0.001). In multivariate analysis, primary disease, height z score < 1.64 at longterm follow-up (LTF) visit, > 4 days of hospitalization since LTF visit, and not being listed as status 1 were predictors of poor physical function. In conclusion, pediatric LT recipients 1-2 years after LT and their parents report lower physical function than a healthy population. Findings suggest practitioners need to routinely assess physical function, and the development of rehabilitation programs may be important. PMID- 26850790 TI - Slicer Endonuclease Argonaute 2 Is a Negative Regulator of Hematopoietic Stem Cell Quiescence. AB - Hematopoietic stem cells (HSCs) are capable of both self-renewing throughout the lifetime of an organism and differentiating into all lineages of the blood system. A proper balance between quiescence and proliferation is critical for the self-renewal and functions of HSCs. The choice of HSCs to remain quiescent or to enter proliferation has been tightly regulated by a variety of cell intrinsic and extrinsic pathways. Identifying molecular players that control HSC quiescence and proliferation may lead to new treatment strategies and therapeutic interventions for hematologic disorders. To identify the functions of the slicer endonuclease Argonaute (Ago) 2 in the physiology of HSCs, we generated Ago2(Hem-KO) mice, that are deficient for Ago2 in HSCs and in their progeny. Analysis of Ago2(Hem-KO) mice indicated that a loss of Ago2 results in reduced HSC pool size and altered frequencies of hematopoietic progenitors. Ago2 deficient HSCs exhibit defective multilineage differentiation capacities and diminished repopulation abilities, in a cell intrinsic manner. Interestingly, Ago2 mutant HSCs remain largely quiescent and show reduced entry into cell cycle. Genome-wide transcriptome studies and gene set enrichment analysis revealed that Ago2 deficient HSCs downregulate the "HSC signature" and upregulate the "lineage signature." Moreover, our analysis on transcription factors (TFs) identified that a loss of Ago2 is sufficient to alter the "molecular signature" and "TF networks" that control the quiescent and proliferative states of HSCs. In essence, our study identified Ago2 as a key determinant of quiescence exit in HSCs. Stem Cells 2016;34:1343-1353. PMID- 26850791 TI - Temporary protection of rainbow trout gill epithelial cells from infection with viral haemorrhagic septicaemia virus IVb. AB - The branchial epithelium is not only a primary route of entry for viral pathogens, but is also a site of viral replication and subsequent shedding may also occur from the gill epithelium. This study investigated the potential of agents known to stimulate innate immunity to protect rainbow trout epithelial cells (RTgill-W1) from infection with VHSV IVb. RTgill-W1 cells were pretreated with poly I:C, FuGENE((r)) HD + poly I:C, lipopolysaccharide (LPS), LPS + poly I:C or heat-killed VHSV IVb and then infected with VHSV IVb 4 days later. Cytopathic effect (CPE) was determined at 2, 3, 4, 7 and 11 days post-infection. Virus in cells and supernatant was detected using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). All of the treatments delayed the onset of CPE (per cent of monolayer destruction), compared with untreated controls; however, killed VHSV or poly I:C combined with LPS was the most effective. Similarly, the detection of viral RNA in the supernatant was delayed, and the quantity was significantly (P < 0.05) reduced by all treatments with the exception of LPS alone (4 days). Unlike many of the other treatments, pretreatment of RTgill-W1 with heat-killed VHSV did not upregulate interferon 1, 2 or MX 1 gene expression. PMID- 26850792 TI - It's All in the Rhythm: The Role of Cannabinoids in Neural Oscillations and Psychosis. AB - Evidence has accumulated over the past several decades suggesting that both exocannabinoids and endocannabinoids play a role in the pathophysiology of schizophrenia. The current article presents evidence suggesting that one of the mechanisms whereby cannabinoids induce psychosis is through the alteration in synchronized neural oscillations. Neural oscillations, particularly in the gamma (30-80 Hz) and theta (4-7 Hz) ranges, are disrupted in schizophrenia and are involved in various areas of perceptual and cognitive function. Regarding cannabinoids, preclinical evidence from slice and local field potential recordings has shown that central cannabinoid receptor (cannabinoid receptor type 1) agonists decrease the power of neural oscillations, particularly in the gamma and theta bands. Further, the administration of cannabinoids during critical stages of neural development has been shown to disrupt the brain's ability to generate synchronized neural oscillations in adulthood. In humans, studies examining the effects of chronic cannabis use (utilizing electroencephalography) have shown abnormalities in neural oscillations in a pattern similar to those observed in schizophrenia. Finally, recent studies in humans have also shown disruptions in neural oscillations after the acute administration of delta-9 tetrahydrocannabinol, the primary psychoactive constituent in cannabis. Taken together, these data suggest that both acute and chronic cannabinoids can disrupt the ability of the brain to generate synchronized oscillations at functionally relevant frequencies. Hence, this may represent one of the primary mechanisms whereby cannabinoids induce disruptions in attention, working memory, sensory motor integration, and many other psychosis-related behavioral effects. PMID- 26850793 TI - Neurothrombectomy in acute ischaemic stroke: a prospective single-centre study and comparison with randomized controlled trials. AB - BACKGROUND AND PURPOSE: In the last few months five multicentre, randomized controlled trials (RCTs) unequivocally showed the superiority of mechanical thrombectomy in large vessel occlusion acute ischaemic stroke compared to systemic thrombolysis. Despite varying inclusion criteria and time intervals from onset to revascularization overall increases of good functional outcome between 55% and 81% were reported. However, only a minority of screened patients (approximately 1%) were eligible for intra-arterial (IA) therapy. METHODS: An investigator-initiated, single-centre, prospective and blinded end-point analysis was performed of 3123 consecutive patients with acute ischaemic stroke presenting between February 2010 and December 2014. RESULTS: One hundred and fifty-four patients [4.9%, age (years) mean (SD), median (interquartile range) 71.2 (+/-14), 74.7 (65.9-81.4)] met the inclusion criteria of sparse early ischaemic signs on initial standard cranial computed tomography (CT) (ASPECT score >=7), large vessel occlusion in the anterior circulation on CT angiography and start of treatment within 6 h of onset of symptoms. After consensual interdisciplinary treatment decisions 130 patients (4.2%) received IA treatment - in the majority stent-assisted thrombectomy in combination with intravenous (IV) recombinant tissue plasminogen activator - and 24 patients (0.7%) standard IV thrombolysis. On 3 months' follow-up an overall significant improvement of disability (P = 0.05) as measured by the modified Rankin Scale was shown in favour of the IA treatment group. Good functional outcome was achieved in about twice as many patients (IA vs. IV, 41.2% vs. 21.2%; P = 0.078). CONCLUSION: By choosing pragmatic inclusion criteria state-of-the-art IA therapy of a specialized tertiary stroke centre can be safely applied under real-world conditions to a higher percentage of patients with similar success to the recently published RCTs. PMID- 26850794 TI - Mannitol in Plants, Fungi, and Plant-Fungal Interactions. AB - Although the presence of mannitol in organisms as diverse as plants and fungi clearly suggests that this compound has important roles, our understanding of fungal mannitol metabolism and its interaction with mannitol metabolism in plants is far from complete. Despite recent inroads into understanding the importance of mannitol and its metabolic roles in salt, osmotic, and oxidative stress tolerance in plants and fungi, our current understanding of exactly how mannitol protects against reactive oxygen is also still incomplete. In this opinion, we propose a new model of the interface between mannitol metabolism in plants and fungi and how it impacts plant-pathogen interactions. PMID- 26850795 TI - What Does It Take to Evolve A Nitrogen-Fixing Endosymbiosis? AB - Plant rhizo- and phyllospheres are exposed to a plethora of nitrogen-fixing bacteria, providing opportunities for the establishment of symbiotic associations. Nitrogen-fixing endosymbioses are most profitable and have evolved more than ten times in the angiosperms. This suggests that the evolutionary trajectory towards endosymbiosis is not complex. Here, we argue that microbe induced cell divisions are a prerequisite for the entrance of diazotrophic prokaryotes into living plant cells. For rhizobia and Frankia bacteria, this is achieved by adapting the readout of the common symbiosis signalling pathway, such that cell divisions are induced. The common symbiosis signalling pathway is conserved in the plant kingdom and is required to establish an endosymbiosis with mycorrhizal fungi. We also discuss the adaptations that may have occurred that allowed nitrogen-fixing root nodule endosymbiosis. PMID- 26850796 TI - Randomized clinical trial of facial acupuncture with or without body acupuncture for treatment of melasma. AB - OBJECTIVE: To evaluate the efficacy of acupuncture treatments in treating facial melasma, contrasting treatments involving facial acupuncture with facial/body acupuncture. METHOD: Women suffering with melasma were randomly assigned into: 1) facial acupuncture (n = 20); or 2) facial/body acupuncture (n = 21). Each group was given 2 sessions per week for 8 weeks. Melasma area and darkness of its pigmentation were assessed using digital images. RESULTS: 95.2% and 90% of participants in facial/body and facial acupuncture, respectively, had decreased melasma areas, with a mean reduction area being 2.6 cm(2) (95%CI 1.6-3.6 cm(2)) and 2.4 cm(2) (95%CI 1.6-3.3 cm(2)), respectively. 66.7% (facial/body acupuncture) and 80.0% (facial acupuncture) of participants had lighter melasma pigmentation compared to their baselines (p-value = 0.482). CONCLUSIONS: Facial acupuncture, with or without body acupuncture, was shown to be effective in decreasing the size of melasma areas. This study is registered with the Thai Clinical Trial Registry (TCTR20140903004). PMID- 26850797 TI - Immediate effect of basic body awareness therapy on heart rate variability. AB - OBJECTIVE: To determine the immediate effect of a Basic Body Awareness Therapy (BAT) session on measures of heart rate variability (HRV) in healthy young people. METHODS: 13 healthy young subjects of both genders, who showed no illnesses related to the autonomic nervous system (ANS) underwent an ANS evaluation before and after conducting a session of BAT. The assessment of ANS activity was conducted through the HR with the aid of Nerve-Express((r)) software. The BAT session lasted for 50 min and was performed by one investigator (blinded to the assessment procedures). RESULTS: After BAT session significant improvement was found in the sympathetic and parasympathetic modulation (p < 0.05), and the general estimate of heart rate variability (p < 0.04). CONCLUSION: BAT was found to be an effective, easy to apply and inexpensive therapeutic technique, able to change ANS in order to improve HR which may suggest better health conditions for participating individuals. PMID- 26850798 TI - Comparison the effect of mefenamic acid and Teucrium polium on the severity and systemic symptoms of dysmenorrhea. AB - BACKGROUND: Primary dysmenorrhea is a prevalent problem and its effects decrease the quality of life in many women across the world. The aim of this study was to research the effect of Teucrium polium compared to mefenamic acid on primary dysmenorrhea. MATERIALS AND METHODS: This triple-blind, randomized, clinical trial study was performed on 70 single female students between 20 and 30 years old educating in Shahid Beheshti University (Tehran, Iran) from October 2014 to February 2014.They were allocated randomly into two groups: In T. polium group (n = 35) who took 250 mg of T. polium powder q6h for the first 3 days of menstruation for two cycles. The second group (n = 35) received 250 mg mefenamic acid,. Dysmenorrhea severity was determined by visual analog scale (VAS). RESULTS: There were no differences between two groups for demographic or descriptive variables. Comprising the VAS showed that the participants in T. polium and mefenamic acid groups had lower significant pain in the 1st and the 2nd months after the treatment (P < 0.05). No side effects were reported in the T. polium and Mefenamic Acid groups. CONCLUSION: T. polium was as effective as mefenamic acid in decreasing the pain severity in primary dysmenorrhea. PMID- 26850799 TI - The acute (immediate) effects of reflexology on arterial compliance in healthy volunteers: A randomised study. AB - BACKGROUND: Reflexology is a widely used complementary therapy. The effects of reflexology on the cardiovascular system are not well characterised. Arterial stiffness (compliance) is a marker of vascular health. This study aimed to evaluate the effects of reflexology on arterial compliance in healthy volunteers. METHODS: 12 healthy volunteers (1 male; 11 female; mean age 44.8 +/- 10.8 yrs) received 10 min of reflexology on each foot in a single-blind randomised study. The main outcome measures were measurements of cardiovascular parameters including heart rate, blood pressure and arterial compliance (augmentation index). RESULTS: Reflexology had no significant effect on heart rate, blood pressure or augmentation index (all p > 0.05). CONCLUSIONS: In healthy volunteers, there were no consistent changes in haemodynamic parameters with a single brief reflexology treatment. Thus from a cardiovascular point of view, reflexology (as delivered) would appear to have a limited (if any) effect on the cardiovascular system. PMID- 26850800 TI - Music used as anti-anxiety intervention for patients during outpatient procedures: A review of the literature. AB - Numerous patients experience anxiety before minor medical procedures [1]. Because patients' experiences are highly individualized, their distress may range from mild to moderate. For a decade, music-based complementary therapy has received increased attention because of the therapeutic and healing environment it creates for patients undergoing invasive procedures [13]. The purpose of this structured literature review is to assess the current evidence regarding the effectiveness of music as an intervention that decreases anxiety for patients undergoing minor medical procedures in outpatient healthcare settings. PMID- 26850801 TI - Implementation of evidence-based practice: A naturopath perspective. AB - Evidence-based practice (EBP), an approach to clinical practice that places emphasis on the use of best available research evidence for decision-making, has been adopted broadly in clinical practice. As a patient-focused approach, EBP promotes the spirit of inquiry. It can also facilitate consistency of care across professional boundaries, and clarify the directions of research. However, over emphasis on systematic reviews and randomised control trials as the "gold standard" for evidence is a major limitation of EBP as it is being practised today. There are also objections to EBP based on epistemological grounds. Complementary and alternative medicine (CAM) therapies often fare unfavourably under the scrutiny of EBP due to the lack of research and inherent differences in healing ideology. Naturopathy is a unique form of CAM, based on both traditional and scientific knowledge. We argue that there is no conflict between naturopathy and EBP. EBP can be adopted as a useful approach to assimilate scientific evidence in naturopathic practices. However, naturopaths need to reconcile tensions between traditional and scientific knowledge in their choice of treatment remedies, while adhering to the naturopathic principles of healing, to benefit the patients. They must also maintain their emphasis on clinical expertise, and also patient preferences and values, in clinical decision-making. PMID- 26850802 TI - Integrative management of pediatric tonsillopharyngitis: An international survey. AB - This survey investigated the management of pediatric tonsillopharyngitis, with a focus on natural remedies. 138 pediatricians, general practitioners and ear-nose throat (ENT) specialists in 7 countries were surveyed by a dedicated questionnaire. A rapid strept test (RST) to diagnose acute tonsillopharyngitis was routinely used by 56/138 participants (41%). The use of RST allowed 200 diagnosis/year compared with 125 diagnosis/year for clinicians who did not use this tool. Homeopathy remedies were prescribed as a supportive therapy by 62% of participants (85/138). Among different homeopathic remedies, SilAtro-5-90 was the most frequently prescribed (53/138, 38%). In the chronic setting, homeopathy was suggested as a supportive therapy by 82/138 participants (59%), phytotherapy by 39 (28%) and vitamins/nutritional supplementation by 51 (37%). The management of tonsillopharyngitis in pediatric patients still remains empiric. Natural remedies, and homeopathy in particular, are used in the management of URTIs. An integrative approach to these infections may help reduce excessive antibiotic prescription. PMID- 26850803 TI - The effects of aromatherapy with lavender essential oil on fatigue levels in haemodialysis patients: A randomized clinical trial. AB - OBJECTIVE: This study was intended to examine the efficacy of lavender essential oil for the alleviation of fatigue in haemodialysis patients. METHODS AND MATERIALS: This randomized clinical trial was conducted on 59 haemodialysis patients in two groups. The routine care group received the routine care, but the experimental group inhaled lavender essence 5% for 10 min, three times a week for 4 consecutive weeks. The Fatigue Severity Scale was used to assess fatigue before the intervention and after the last intervention in the second and fourth weeks. RESULTS: No statistically significant differences were observed between the two groups in terms of the fatigue scores before, and after the last intervention in the second and fourth weeks. CONCLUSION: Our result does not support other studies suggesting that lavender essential oil is effective on fatigue in haemodialysis patients. This conflicting result can mostly be ascribed to a variety of factors such as duration of aromatherapy and differences in concentrations of lavender essential oil. PMID- 26850804 TI - Investigating the effects of a multidimensional exercise program on symptoms and antiinflammatory status in female patients with ankylosing spondylitis. AB - OBJECTIVE: The purpose of this study is to investigate the effects of a multidimensional exercise program on symptoms and antiinflammatory status in female patients with ankylosing spondylitis (AS). METHODS: The BATH Indexes, Dougados Functional Index (DFI), Health Assessment Questionnaire in Spondyloarthopathies (HAQ-S), Ankylosing Spondylitis Quality of Life (ASQoL) and Beck Depression Inventory (BDI) were used to evaluate twenty-four female AS patients. ESR, CRP, TNF-alpha and IL-6 were also analyzed. All patients were assessed at baseline and with 3 weeks intervals till 12 week. A multidimensional exercise program was applied for three times a week. RESULTS: There were significant differences in Bath Ankylosing Spondylitis Global Index (BAS-G) and Disease Activity Index (BASDAI), HAQ-S, ASQoL and BDI scores (p < 0.05). The level of the ESR, CRP and IL-6 fluctuated slightly. There was only significant difference at 3 and 12 weeks as compared to baseline levels in TNF-alpha values (p = 0.048, p < 0.001). CONCLUSION: We concluded that multidimensional exercise program should be taken into consideration for AS patients due to its positive effects on symptoms and antiinflammatory effects. PMID- 26850805 TI - Effects of pomegranate extract supplementation on inflammation in overweight and obese individuals: A randomized controlled clinical trial. AB - The study was designed to determine the effect of thirty days of pomegranate extract oral supplementation on plasma inflammatory and oxidative stress biomarkers as well as serum metabolic profiles, in overweight and obese individuals. In this randomized, double-blind, placebo-controlled study 48 obese and overweight participants were randomly assigned to receive either 1000 mg of pomegranate extract, or a placebo, daily for 30 days. At baseline, and after 30 days of treatment, anthropometric parameters, dietary intake, plasma concentrations of malondialdehyde, interleukin-6 and hyper sensitive-C reactive protein and levels of serum lipids, glucose and insulin were assessed. Thirty days of PE supplementation resulted in a significant decrease in mean serum levels of glucose, insulin, total cholesterol, LDL-C, and plasma MDA, IL-6 and hs CRP. HDL-C significantly increased following the PE versus the PL intervention. Our study suggests that pomegranate extract consumption may reduce complications linked with obesity. PMID- 26850806 TI - The use of aromasticks to help with sleep problems: A patient experience survey. AB - To document the use of aromasticks to facilitate sleep in a cancer centre in the UK. Sleep disturbance is a common problem amongst patients diagnosed with cancer. Essential oils may be inhaled by means of an aromastick (a personal inhaler device containing essential oils) as a means of improving sleep. A prospective audit of aromasticks given to help facilitate sleep. Sixty-five aromasticks were given out over a 13 week period. 94% of patients reported that they did use their aromastick to help them sleep and 92% reported that they would continue to do so. An improvement of at least one point on a Likert scale measuring sleep quality was shown by 64% of patients following the use of an aromastick. Bergamot (Citrus bergamia) and sandalwood (Santalum austrocaladonicum); and frankincense (Boswellia carterii), mandarin (Citrus reticulata) and lavender (Lavandula angustifolia) were the essential oils used in the two blends chosen by patients. PMID- 26850807 TI - Prescription medication use in a chiropractic training clinic: Cause for vigilance. AB - PURPOSE: The concurrent use of CAM therapies with traditional allopathic medical practice is increasing. This study investigates the concurrent use of prescription medication in patients attending a chiropractic student teaching clinic for the first time. The need for practitioners to be aware of the side effects of prescribed medication patients are using is discussed. METHODS: Cross sectional study of 1008 new patient consultations at a university chiropractic teaching clinic. RESULTS: 549 prescription medications being used by 330 patients were included in the analysis. A total of 104 individual medications were identified of which 69 listed headache as a potential side effect of their use. 57 of 116 (49%) of patients seeking care for the treatment of headache were concurrently using these medications. CONCLUSIONS: Patients presenting to the university chiropractic teaching clinic may be seeking care for symptoms attributed to prescription medication. The requirement that practitioners be aware of the side effects of prescribed medication patients are using is raised. PMID- 26850808 TI - Therapeutic touch for nausea in breast cancer patients receiving chemotherapy: Composing a treatment. AB - BACKGROUND AND OBJECTIVE: Therapeutic touch (TT) is independent nursing intervention which is effective on nausea induced by chemotherapy but technique, steps and variables affected by this therapy are not yet well known. The aim of this study was to elicit descriptions of how TT is used with cancer patients, providing a basis for the systematic use and evaluation of TT with patients. MATERIALS AND METHOD: In this research, 108 patients were examined with intentional sampling and random allocation in 3 groups (control, placebo and intervention) in 2013 (each group 36). Intervention received therapeutic touch (touching of first energy layer) and demographic form, visual analog scale (VAS) for intensity of nausea, check list for duration and times of nausea in the morning, noon, afternoon and night at acute phase were used. Data were analyzed by Kruskal Wallis, chi(2) and analysis of variance (ANOVA). RESULTS: Duration, frequency and intensity of nausea were significantly lower in the test group (P < 0.001, P < 0.001 and P < 0.001). The mean duration of intervention (whole process) was 21.38 min [SD 6.04]. In 69.4% of women there was a need for re intervention after reassessment phase. CONCLUSION: Results of this randomized control trial showed that TT is effective on duration, times and intensity of nausea; therefore, TT can be used as an alternative method for patients who are willing to use this technique. PMID- 26850809 TI - Effects of yoga practice on muscular endurance in young women. AB - The aim of this study was to verify the effects of a systematized yoga practice on muscular endurance in young women. Twenty six women (24 +/- 3.5 years old) participated in six weeks of yoga classes, and twenty one women (25 +/- 5.1 years old) participated as the control group. The yoga intervention was composed of eighteen sessions, three times per week, at 1 h per session. The muscular endurance of upper limbs (push-up) and abdominal (sit-up) was assessed through the protocol suggested by Gettman (1989) [1] and Golding, Myers and Sinning (1989) [2] to the maximum repetitions performed in 1 min. To verify the significant differences intra groups and between groups a SPANOVA was performed, and the level of significance was p <= 0.05. The findings suggest that yoga provides improvement in upper limb and in abdominal muscular endurance. PMID- 26850810 TI - Multi-site evaluation of a complementary, spiritually-based intervention for Veterans: The Mantram Repetition Program. AB - BACKGROUND: Mental and physical symptoms affect Veterans' quality of life. Despite available conventional treatments, an increasing number of Veterans are seeking complementary approaches to symptom management. Research on the Mantram Repetition Program (MRP), a spiritually-based intervention, has shown significant improvements in psychological distress and spiritual well-being in randomized trials. However, these findings have not been replicated in real-world settings. METHODS: In this naturalistic study, we analyzed outcomes from 273 Veterans who participated in MRP at six sites and explored outcomes based on facilitator training methods. Measures included satisfaction and symptoms of anxiety, depression, and somatization using the Brief Symptom Inventory-18; Functional Assessment of Chronic Illness Therapy-Spiritual Well-being questionnaire; and the Mindfulness Attention Awareness Scale. RESULTS: There were significant improvements in all outcomes (p's < .001) regardless of how facilitators were trained. Patient satisfaction was high. CONCLUSION: The MRP was disseminated successfully yielding improvements in psychological distress, spiritual well being, and mindfulness. PMID- 26850811 TI - Mind body therapies in rehabilitation of patients with rheumatic diseases. AB - Mind body therapies (MBT) share a global approach involving both mental and physical dimensions, and focus on relationship between brain, mind, body and behavior and their effects on health and disease. MBT include concentration based therapies and movement based therapies, comprising traditional Oriental practices and somatic techniques. The greatest part of rheumatic diseases have a chronic course, leading to progressive damages at musculoskeletal system and causing physical problems, psychological and social concerns. Thus, rheumatic patients need to be treated with a multidisciplinary approach integrating pharmacological therapies and rehabilitation techniques, that not should only aim to reduce the progression of damages at musculoskeletal system. Thus, MBT, using an overall approach, could be useful in taking care of the overall health of the patients with chronic rheumatic diseases. This review will deal with different MBT and with their effects in the most common chronic rheumatic diseases (Rheumatoid Arthritis, Ankylosing Spondylitis, Fibromyalgia Syndrome). PMID- 26850812 TI - Knee osteoarthritis pain in the elderly can be reduced by massage therapy, yoga and tai chi: A review. AB - BACKGROUND AND METHODS: This is a review of recently published research, both empirical studies and meta-analyses, on the effects of complementary therapies including massage therapy, yoga and tai chi on pain associated with knee osteoarthritis in the elderly. RESULTS: The massage therapy protocols have been effective in not only reducing pain but also in increasing range of motion, specifically when moderate pressure massage was used and when both the quadriceps and hamstrings were massaged. The yoga studies typically measured pain by the WOMAC. Most of those studies showed a clinically significant reduction in pain, especially the research that focused on poses (e.g. the Iyengar studies) as opposed to those that had integrated protocols (poses, breathing and meditation exercises). The tai chi studies also assessed pain by self-report on the WOMAC and showed significant reductions in pain. The tai chi studies were difficult to compare because of their highly variable protocols in terms of the frequency and duration of treatment. DISCUSSION: Larger, randomized control trials are needed on each of these therapies using more standardized protocols and more objective variables in addition to the self-reported WOMAC pain scale, for example, range of-motion and observed range-of-motion pain. In addition, treatment comparison studies should be conducted so, for example, if the lower-cost yoga and tai chi were as effective as massage therapy, they might be used in combination with or as supplemental to massage therapy. Nonetheless, these therapies are at least reducing pain in knee osteoarthritis and they do not seem to have side effects. PMID- 26850813 TI - Evaluation of the efficacy of a polyherbal mouthwash containing Zingiber officinale, Rosmarinus officinalis and Calendula officinalis extracts in patients with gingivitis: A randomized double-blind placebo-controlled trial. AB - BACKGROUND: Gingivitis is a highly prevalent periodontal disease resulting from microbial infection and subsequent inflammation. The efficacy of herbal preparations in subjects with gingivitis has been reported in some previous studies. OBJECTIVE: To investigate the efficacy of a polyherbal mouthwash containing hydroalcoholic extracts of Zingiber officinale, Rosmarinus officinalis and Calendula officinalis (5% v/w) compared with chlorhexidine and placebo mouthwashes in subjects with gingivitis. METHODS: Sixty patients participated in this randomized double-blind placebo-controlled trial and were randomly assigned to the polyherbal mouthwash (n = 20), chlorhexidine mouthwash (n = 20) or placebo mouthwash (n = 20). Participants were instructed to use the mouthwash twice a day (after breakfast and dinner) for 30 s for a period of two weeks. Gingival and plaque indices were assessed using MGI, GBI and MQH scales at baseline, day 7 and day 14 of the trial. RESULTS: There were significant improvements in all assessed efficacy measures i.e. MGI, GBI and MQH scores from baseline to the end of trial in both polyherbal and chlorhexidine mouthwash groups; however, the scores remained statistically unchanged in the placebo group. MGI, BGI and MQH scores in the treatment groups were significantly lower compared with those of the control group at both day 7 and day 14 of the trial. However, there was no significant difference between the polyherbal and chlorhexidine groups, neither at day 7 nor day 14 of the trial. Polyherbal mouthwash was safe and there was neither report of adverse reactions, nor any drop-out during the course of study. CONCLUSION: Polyherbal mouthwash containing hydroalcoholic extracts of Z. officinale, R. officinalis and C. officinalis (5%) was effective in the treatment of gingivitis and its efficacy was comparable to that of chlorhexidine mouthwash. PMID- 26850814 TI - A Case of Bilateral Cystic Partially Differentiated Nephroblastoma vs Cystic Wilms' Tumor: Highlighting a Diagnostic Dilemma. AB - Cystic partially differentiated nephroblastoma (CPDN) is a rare multicystic renal tumor along the spectrum of cystic nephroma and cystic Wilms' tumor. There have only been two previously reported cases of bilateral CPDN in the literature. We present here a case of bilateral CPDN vs cystic Wilms' tumor treated with neoadjuvant and adjuvant chemotherapy in addition to a bilateral partial nephrectomy. We also review the relevant literature regarding CPDN in an effort to aid in diagnosis and management of these rare cystic renal tumors. PMID- 26850815 TI - The Memorial Sloan Kettering Cancer Center Recommendations for Prostate Cancer Screening. AB - The Memorial Sloan Kettering Cancer Center (MSKCC) recommendations on prostate cancer screening were developed in response to three limitations of previous screening guidelines: insufficient evidence base, failure to link screening with treatment, and lack of risk stratification. The objective of the recommendations is to provide a schema for prostate cancer screening that maximizes the benefits, in terms of reduction in prostate cancer-specific mortality, and minimizes the harms, in terms of overdiagnosis and overtreatment. We recommend the following schema for men choosing to be screened following informed decision-making: starting at age 45, prostate-specific antigen (PSA) without digital rectal examination. If PSA >= 3 ng/mL: consider prostate biopsy; if PSA >= 1 but < 3 ng/mL: return for PSA testing every 2-4 years; if PSA < 1 ng/mL: return for PSA testing at 6-10 years. PSA testing should end at age 60 for men with PSA <= 1 ng/ mL; at 70, unless a man is very healthy and has a higher than average PSA; at 75 for all men. The decision to biopsy a man with a PSA > 3 ng/mL should be based on a variety of factors including repeat blood draw for confirmatory testing of the PSA level, digital rectal examination results, and workup for benign disease. Additional reflex tests in blood such as a free-to-total PSA ratio, the Prostate Health Index, or 4Kscore, or urinary testing of PCA3, can also be informative in some patients. The best evidence suggests that more restricted indication for prostate biopsy and a more focused approach to pursue screening in men at highest risk of lethal cancer would retain most of the mortality benefits of aggressive screening schema, while importantly reducing harms from overdetection and overtreatment. PMID- 26850816 TI - Contemporary Evaluation and Management of Upper Tract Urothelial Cancer. AB - Radical nephroureterectomy with en bloc bladder cuff excision and regional lymphadenectomy is the gold standard for the management of high-grade and high risk upper tract urothelial carcinomas. There are a few prospective randomized controlled studies in this uncommon and often aggressive disease to support level 1 management guidelines. However, recent developments in imaging, minimally invasive techniques, lymphatic dissemination, and bladder cancer prevention raise the hope for improved risk stratification and treatments without compromising, and hopefully improving, oncological outcomes. Multimodality approaches in terms of neoadjuvant, adjuvant topical, and systemic chemotherapeutic regimens are promising, with 2 prospective trials either open or in development. PMID- 26850817 TI - Investigation of salt formation between memantine and pamoic acid: Its exploitation in nanocrystalline form as long acting injection. AB - In the present work, we prepared memantine-pamoic acid (MEM-PAM) salt by counter ion exchange in the aqueous phase to reduce the water solubility of MEM hydrochloride (native form) to make it suitable for long acting injection. The ratio of MEM to PAM in salt formation was optimized to maximize the loading efficiency and complexation efficiency. The 2:1 molar ratio of MEM to PAM salt form displayed nearly 95% complexation efficiency and 50% drug loading. The solubility was decreased by a ~1250 folds. Thermo Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), and Powder X-ray Diffraction Analysis (PXRD) studies revealed the formation of new solid phase. Additionally, Nuclear Magnetic Resonance (NMR) spectroscopy confirmed the anhydrous nature of the salt form. Through Fourier transformation infrared spectroscopy (FT-IR) we identified the molecular interactions. Further, the microcrystals of the salt were transformed into nanocrystals (NCs) using high pressure homogenization. The particle size distribution and atomic force microscopy confirmed the monodispersed and spherical shape of the NCs. The in vitro dissolution studies were performed under sink condition in phosphate buffer saline pH 6.8. The results of MTT assay in murine fibroblast 3T3 cell line show that the NCs were less cytotoxic and more tolerable than plain MEM HCl. The in vivo performance of NCs administered as i.m. injection at three different doses in female Sprague Dawley rats showed that the plasma levels lasted till the 24th day of the study. The pharmacokinetic parameters AUC0-infinity and Cmax increased linearly with increasing dose. Therefore, the results suggest that injectable NCs could represent a therapeutic alternative for the treatment of AD. PMID- 26850818 TI - Facilitators of recovery for step-up and step-down clients of a sub-acute residential mental health service. AB - BACKGROUND: Sub-acute residential mental health services provide care for people who are not acutely unwell but require more support than generally available when living in the community. Little is known about how these services facilitate recovery and whether these facilitators differ for clients entering from the community (step-up) or from inpatient settings (step-down). AIM: To identify features of a sub-acute residential service that have assisted step-up and step down clients in their recovery. METHOD: Semi-structured interviews were conducted with 16 step-up and 21 step-down clients. Interview transcripts were examined using an inductive, semantic content analysis approach. RESULTS: Themes identified included the community context, personal support, the formal program offered and assistance in personal recovery processes, with the level of support for these themes differing for step-up and step-down clients. CONCLUSIONS: Step up and step-down clients have differing needs to be addressed in a sub-acute service. These services can better meet the needs of clients if they are aware of the setting the client has come from and tailor their services accordingly. Step up clients prefer support in developing social skills and illness management techniques; step-down clients prefer a less structured environment with assistance in living skills and personal processes of recovery. PMID- 26850819 TI - Adverse events of gastric electrical stimulators recorded in the Manufacturer and User Device Experience (MAUDE) Registry. AB - : The role of gastric electrical stimulation for patients with refractory symptoms of gastroparesis remains controversial. Open label studies suggest benefit while randomized controlled trials did not demonstrate differences between active and sham intervention. Using a voluntary reporting system of the Federal Drug Administration, we examined the type and frequency of adverse events. METHODS: We conducted an electronic search of the Manufacturer and User Device Experience (MAUDE) databank using the keyword 'Enterra' for the time between January of 2001 and October of 2015. We abstracted information about the year of stimulator implantation, the year and type of adverse effect, the resulting intervention and outcome if available. RESULTS: A total of 1587 entries described adverse effects related the GES. Only 36 of the reports listed perioperative complications. The vast majority described problems that could be classified as patient concerns, local complications, or system failure. The most common problem related lack or loss of efficacy, followed by pain or complications affecting the pocket site. A subset of 801 reports provided information about the time between system implant and registration of concerns, which gradually declined over time. More than one third (35.7%) of the reported adverse events prompted surgical correction. CONCLUSION: The number of voluntarily reported adverse events and the high likelihood of repeated surgical interventions clearly demonstrate the potential downside of gastric electrical stimulation. Physicians considering this intervention will need to carefully weigh these risks and include this information when counseling or consenting patients. PMID- 26850820 TI - Ensemble-Based Virtual Screening and Experimental Validation of Inhibitors Targeting a Novel Site of Human DNMT1. AB - Human DNA methyltransferase1 (hDNMT1) is responsible for preserving DNA methylation patterns that play important regulatory roles in differentiation and development. Misregulation of DNA methylation has thus been linked to many syndromes, life style diseases, and cancers. Developing specific inhibitors of hDNMT1 is an important challenge in the area since the currently targeted cofactor and substrate binding site share structural features with various proteins. In this work, we generated a structural model of the active form of hDNMT1 and identified that the 5-methylcytosine (5-mC) binding site of the hDNMT1 is structurally unique to the protein. This site has been previously demonstrated to be critical for methylation activity. We further performed multiple nanosecond time scale atomistic molecular dynamics simulations of the structural model followed by virtual screening of the Asinex database to identify inhibitors targeting the 5-mC site. Two compounds were discovered that inhibited hDNMT1 in vitro, one of which also showed inhibition in vivo corroborating the screening procedure. This study thus identifies and attempts to validate for the first time a unique site of hDNMT1 that could be harnessed for rationally designing highly selective and potent hypomethylating agents. PMID- 26850822 TI - Joint instability leads to long-term alterations to knee synovium and osteoarthritis in a rabbit model. AB - OBJECTIVES: Joint instability is believed to promote early osteoarthritic changes in the knee. Inflammatory reactions are associated with cartilage degradation in osteoarthritis (OA) but their possible synergistic or additive effects remain largely unexplored. The goal of the present study was to investigate the in vivo effects of Botulinum Toxin A (BTX-A) induced joint instability on intraarticular alterations in an otherwise intact rabbit knee joint model. METHODS: Ten 1-year old female New Zealand White rabbits (average 5.7 kg, range 4.8-6.6 kg) were randomly assigned to receive three monthly unilateral intramuscular injections of BTX-A (experimental group), or no treatment (control group). After 90 days, all knees were analyzed for specific mRNA levels using RT-qPCR. The synovium and cartilage tissue was assessed for histological alterations using the OARSI scoring system. RESULTS: Cartilage and synovial histology showed significant higher OARSI scores in the BTX-A group animals compared to the untreated controls and contralateral limbs. There were no differences between the untreated control and the contralateral experimental limbs. Gene expression showed significant elevations for collagen I, collagen III, nitric oxide, TGF-beta, IL-1 and IL-6 compared to the healthy controls. CONCLUSION: BTX-A induced joint instability in a muscle weakness model uniquely leads to alterations in gene expression and histological changes in the synovial membranes and cartilage in otherwise intact knee joints. These results lead to the conclusion that joint instability may promote an inflammatory intraarticular milieu, thereby contributing to the development of OA. PMID- 26850821 TI - Coupled Heterogeneities and Their Impact on Parasite Transmission and Control. AB - Most host-parasite systems exhibit remarkable heterogeneity in the contribution to transmission of certain individuals, locations, host infectious states, or parasite strains. While significant advancements have been made in the understanding of the impact of transmission heterogeneity in epidemic dynamics and parasite persistence and evolution, the knowledge base of the factors contributing to transmission heterogeneity is limited. We argue that research efforts should move beyond considering the impact of single sources of heterogeneity and account for complex couplings between conditions with potential synergistic impacts on parasite transmission. Using theoretical approaches and empirical evidence from various host-parasite systems, we investigate the ecological and epidemiological significance of couplings between heterogeneities and discuss their potential role in transmission dynamics and the impact of control. PMID- 26850825 TI - Integration of the viral genome into the host cell genome: a double-edged sword. PMID- 26850824 TI - Spectrum of excess mortality due to carbapenem-resistant Klebsiella pneumoniae infections. AB - Patients infected or colonized with carbapenem-resistant Klebsiella pneumoniae (CRKp) are often chronically and acutely ill, which results in substantial mortality unrelated to infection. Therefore, estimating excess mortality due to CRKp infections is challenging. The Consortium on Resistance against Carbapenems in K. pneumoniae (CRACKLE) is a prospective multicenter study. Here, patients in CRACKLE were evaluated at the time of their first CRKp bloodstream infection (BSI), pneumonia or urinary tract infection (UTI). A control cohort of patients with CRKp urinary colonization without CRKp infection was constructed. Excess hospital mortality was defined as mortality in cases after subtracting mortality in controls. In addition, the adjusted hazard ratios (aHR) for time-to-hospital mortality at 30 days associated with infection compared with colonization were calculated in Cox proportional hazard models. In the study period, 260 patients with CRKp infections were included in the BSI (90 patients), pneumonia (49 patients) and UTI (121 patients) groups, who were compared with 223 controls. All cause hospital mortality in controls was 12%. Excess hospital mortality was 27% in both patients with BSI and those with pneumonia. Excess hospital mortality was not observed in patients with UTI. In multivariable analyses, BSI and pneumonia compared with controls were associated with aHR of 2.59 (95% CI 1.52-4.50, p <0.001) and 3.44 (95% CI 1.80-6.48, p <0.001), respectively. In conclusion, in patients with CRKp infection, pneumonia is associated with the highest excess hospital mortality. Patients with BSI have slightly lower excess hospital mortality rates, whereas excess hospital mortality was not observed in hospitalized patients with UTI. PMID- 26850823 TI - The association between MR T1rho and T2 of cartilage and patient-reported outcomes after ACL injury and reconstruction. AB - OBJECTIVE: To determine if cartilage T1rho and T2 relaxation time measures after ACL injury and prior to reconstruction (baseline) are associated with patient reported outcomes at baseline, 6-months, and 1-year after surgery. DESIGN: Fifty four ACL-injured participants were scanned in both knees at baseline using 3T MR T1rho and T2 mapping. Participants also completed Knee-injury and Osteoarthritis Outcome Score (KOOS) and Marx activity level questionnaires at baseline, 6 months, and 1-year after reconstruction. The difference between cartilage T1rho or T2 of the injured and contralateral knee (side-to-side difference, SSD) was calculated to account for physiological variations among patients. Linear regression models were built to evaluate the association between the baseline SSD T1rho or T2 and KOOS or Marx at all time points. RESULTS: Higher baseline SSD T1rho posterolateral tibia (pLT) was associated with worse KOOS in all subscales except symptoms at baseline, worse KOOS pain at 6-months, and worse KOOS in all subscales except sports function at 1-year. Higher baseline SSD T2 femoral trochlea (TrF) was associated with worse KOOS activities of daily living (ADL) at 1-year. Higher baseline SSD T1rho pLT was associated with lower Marx activity level at 1-year. More severe cartilage lesions, as assessed by Whole-Organ MRI Scoring (WORMS), was significantly associated with worse KOOS pain at 6-months and 1-year. CONCLUSION: T1rho and T2 of cartilage after ACL injury were associated with KOOS after injury and both KOOS and Marx after reconstruction. Such associations may help clinicians stratify outcomes post-injury, and thus, improve patient management. PMID- 26850826 TI - Predictors of outcome in ICU patients with septic shock caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae. AB - The aim of this study was to identify factors associated with mortality in intensive care unit patients with Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-Kp) septic shock. A retrospective analysis of intensive care unit patients with KPC-Kp infection and septic shock observed in a large teaching hospital from November 2010 to December 2014 was performed. A total of 111 patients were included in the study. The most frequent source of infection was unknown-focus bacteraemia in 53 patients (47.7%). The rate of resistance to colistin was 51.3%; 30-day mortality was reported for 44 patients (39.6%). Surviving patients were more frequently treated with an initial therapy (within 24 hours) including two or more antibiotics displaying in vitro activity against the isolated KPC-Kp strain (41.8 vs. 18.1%, p 0.01) and were also more likely to receive a definitive therapy including two or more in vitro active antibiotics (85.1 vs. 15.9%, p <0.001). Cox regression analysis revealed that a colistin containing antibiotic regimen (hazard ratio (HR) 0.21, confidence interval (CI) 95% 0.05-0.72, p <0.001), use of two or more in vitro active antibiotics as definite therapy (HR 0.08, CI 95% 0.02-0.21, p <0.001) and control of removable source of infection (HR 0.14, CI 95% 0.04-0.25, p <0.001) were associated with favourable outcome; colistin resistance (HR 8.09, CI 95% 3.14-11.23, p 0.001) and intra-abdominal source of infection (HR 2.92, CI 95% 2.11-4.12, p 0.002) were associated with death. In conclusion, use of a definitive therapy with at least two antibiotics displaying in vitro activity against the KPC-Kp isolates was the most important determinant of favourable outcome, whilst isolation of colistin resistant strains was associated with death in septic patients with KPC-Kp infection. PMID- 26850827 TI - Should we provide acute care in single or double room occupancy? PMID- 26850828 TI - Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins. AB - The emergence of infections by multidrug-resistant (MDR) Gram-negative bacteria, which is accompanied by considerable mortality due to inappropriate therapy, led to the investigation of whether adjunctive treatment with one polyclonal IgM enriched immunoglobulin preparation (IgGAM) would improve outcomes. One hundred patients in Greece with microbiologically confirmed severe infections by MDR Gram negative bacteria acquired after admission to the Intensive Care Unit and treated with IgGAM were retrospectively analysed from a large prospective multicentre cohort. A similar number of patient comparators well-matched for stage of sepsis, source of infection, appropriateness of antimicrobials and co-morbidities coming from the same cohort were selected. All-cause 28-day mortality was the primary end point; mortality by extensively drug-resistant (XDR) pathogens and time to breakthrough bacteraemia were the secondary end points. Fifty-eight of the comparators and 39 of the IgGAM-treated cases died by day 28 (p 0.011). The OR for death under IgGAM treatment was 0.46 (95% CI 0.26-0.85). Stepwise regression analysis revealed that IgGAM was associated with favourable outcome whereas acute coagulopathy, cardiovascular failure, chronic obstructive pulmonary disease and chronic renal disease were associated with unfavourable outcome. Thirty-nine of 62 comparators (62.9%) were infected by XDR Gram-negative bacteria and died by day 28 compared with 25 of 65 cases treated with IgGAM (38.5%) (p 0.008). Median times to breakthrough bacteraemia were 4 days and 10 days, respectively (p <0.0001). Results favour the use of IgGAM as an adjunct to antimicrobial treatment for the management of septic shock caused by MDR Gram-negative bacteria. A prospective randomized trial is warranted. PMID- 26850829 TI - Immunogenicity difference between two hepatitis E vaccines derived from genotype 1 and 4. AB - We investigated the immunogenicity difference between hepatitis E vaccine p239 derived from hepatitis E virus (HEV) genotype 1 and vaccine p179 derived from HEV genotype 4; and the presence of genotype-specific neutralizing epitopes. HEV ORF2 recombinant proteins (p166W01, p166Mex, p166US and p166Chn) derived from the four HEV genotypes were used to detect anti-HEV IgGs in sera of mice and humans vaccinated with p179 or p239 and in sera of rhesus monkey challenged with HEV genotype 1 or 4 strains. Then monoclonal antibodies (mAbs) against genotype 1 or 4 ORF2 recombinant proteins were prepared and their immunoreactivity was assessed using ELISA and Western blotting; their neutralizing activity was evaluated by an in vitro PCR-based neutralization assay. The results revealed significant immunogenicity difference between the two vaccines: p239-induced IgGs reacted more strongly against p166W01 and p166Mex than against p166US and p166Chn in mice and humans. By contrast, p179-induced IgGs showed a stronger reactivity against p166US and p166Chn than against p166W01 and p166Mex. This difference has also been observed in the sera of rhesus monkeys challenged with HEV genotype 1 or 4 strains. Moreover, besides the two common neutralizing mAbs 3G1 and 5G5, two genotype-specific neutralizing mAbs, 2B1 and 4C5, were obtained. 2B1 could specifically bind to recombinant proteins derived from genotypes 1 and 2 and neutralized only genotypes 1 and 2 strains, while 4C5 immunoreacted specifically against recombinant proteins derived from genotypes 3 and 4 and neutralized only genotypes 3 and 4 strains. These findings revealed the existence of immunogenicity difference between the p179 and p239 vaccines and demonstrated that this difference could be due to the presence of HEV genotype-specific neutralization epitopes. PMID- 26850831 TI - [Access to high-cost drugs in Brazil from the perspective of physicians, pharmacists and patients]. AB - OBJECTIVE: To explore perceptions on access to medication supplied by the Specialized Component of Pharmaceutical Assistance (CEAF) within the Brazilian Unified Health System (which includes high-cost drugs) by the actors involved in the healthcare services of this component. METHOD: A descriptive, qualitative study was carried out by using a focal group with 7 users and 11 semi-structured interviews with health professionals (physicians and pharmacist) in the state of Santa Catarina. RESULTS: According to the participants, access to medicines had improved. Two main perceptions of the CEAF Clinical Guidelines were identified: the requirements constitute a bureaucracy that limits access, and the requisites increase the demand for tests and specialized healthcare services, exceeding the capacity of the healthcare services network. These assumptions generated the search for other means of access that revealed a lack of information and understanding of the right to health among the users. In addition, according to the participants, because of the difficulties of accessing services as a whole, full access to CEAF medicines is a goal that remains to be achieved. CONCLUSION: Although access to CEAF medicines has improved, there are still some difficulties in guaranteeing treatment access and comprehensiveness. PMID- 26850830 TI - Benzothiazepinecarboxamides: Novel hepatitis C virus inhibitors that interfere with viral entry and the generation of infectious virions. AB - Upon screening synthetic small molecule libraries with the infectious hepatitis C virus (HCV) cell culture system, we identified a benzothiazepinecarboxamide (BTC) scaffold that inhibits HCV. A structure-activity relationship (SAR) study with BTCs was performed, and modifications that led to nanomolar antiviral activity and improved the selective index (CC50/EC50) by more than 1000-fold were identified. In addition, a pharmacophore modeling study determined that the tricyclic core and positive charge on the piperidine moiety were essential for antiviral activity. Furthermore, we demonstrated that BTC interferes with HCV glycoprotein E1/E2-mediated viral entry and the generation of infectious virions by using HCV pseudoparticle and cell culture supernatant transfer assays, respectively. BTC showed potent antiviral activity against HCV genotype 2 (EC50 = 0.01 +/- 0.01 MUM), but was less potent against a genotype 1/2 chimeric virus (EC50 = 2.71 +/- 0.05 MUM), which expressed the structural proteins of HCV genotype 1. In summary, we identified, optimized, and characterized novel BTC inhibitors that interfere with early and late steps of the HCV viral life cycle. PMID- 26850832 TI - Myocardial effects of fetal endoscopic tracheal occlusion in lambs with CDH. AB - INTRODUCTION: Fetal endoscopic tracheal occlusion in congenital diaphragmatic hernia (CDH) may reduce pulmonary hypertension and ameliorate postnatal cardiac output. The effects of sustained early (ETO) and late (LTO) tracheal occlusion on left ventricular (LV) cells in the lamb model have not been described. MATERIALS AND METHODS: CDH was created in lambs at 70 days' gestation (term = 145 days). ETO (85 days) or LTO (105 days) was sustained till term. After cesarean section (140 days) fetuses were euthanized and hearts harvested. LV myocardial cells were studied by histological and immunofluorescence (TGF-beta 1, endothelin-1) assays in CDH, ETO, LTO, and the control group (two subjects per group). Small intramyocardial arteries were evaluated by traditional histology. RESULTS: LV myocardial histology in CDH and LTO was similar. ETO-induced LV myocardial cell enlargement and increased endothelin-1 and TGF-beta 1 staining; a weaker immunofluorescence signal was observed in LTO compared with ETO. Myocardial vascular wall thickness was greater in CDH than in controls. ETO was associated with a vascular wall thickness within the range of controls. CONCLUSION: With only two fetuses in each group, only an explorative evaluation was possible. The time point at which TO is performed seems to have an effect on cardiac morphology. Functional studies as well as confirmation in clinical samples are mandatory. PMID- 26850833 TI - THBS1 is induced by TGFB1 in the cancer stroma and promotes invasion of oral squamous cell carcinoma. AB - BACKGROUND: THBS1 (thrombospondin-1) is the extracellular matrix (ECM) protein that affects diverse cellular activities. It constitutes the tumor stroma, but the role of THBS1 in oral squamous cell carcinoma (OSCC) development is unclear. The aim of this study was to clarify the relevance of THBS1 in the pathogenesis of OSCC. MATERIALS AND METHODS: The expression of THBS1 was examined in 44 OSCC by immunohistochemical analysis and in 43 OSCC by cDNA microarray analysis. Cell culture experiments were conducted using human OSCC cell lines HSC3 and HO1N1 and mouse fibroblast ST2 cells to examine the effect of TGFB1 on THBS1 expression, and the effect of THBS1 on cellular behaviors. RESULTS: THBS1 was specifically induced in the tumor microenvironment of OSCC. THBS1 appeared to be produced mainly by the stromal cells, but also by OSCC cells. TGFB1 stimulated THBS1 expression in ST2, primary fibroblasts, and the OSCC cells. THBS1 promoted migration and invasion of HSC3 and HO1N1 in transwell migration assays. THBS1 stimulated the expression of MMP3 (matrix metalloprotease 3), MMP9, MMP11, and MMP13 in ST2 cells and MMP3, MMP11, and MMP13 in HO1N1 cells. The RGD peptide suppressed the THBS1-stimulated migration and upregulation of MMP11 and MMP13. CONCLUSIONS: THBS1 is a tumor-specific ECM protein that is induced by TGFB1 and promotes migration of cancer cells and stimulates the expression of MMPs partly through the integrin signaling, thereby favoring OSCC invasion. PMID- 26850834 TI - Hybridization during altitudinal range shifts: nuclear introgression leads to extensive cyto-nuclear discordance in the fire salamander. AB - Ecological models predict that, in the face of climate change, taxa occupying steep altitudinal gradients will shift their distributions, leading to the contraction or extinction of the high-elevation (cold-adapted) taxa. However, hybridization between ecomorphologically divergent taxa commonly occurs in nature and may lead to alternative evolutionary outcomes, such as genetic merger or gene flow at specific genes. We evaluate this hypothesis by studying patterns of divergence and gene flow across three replicate contact zones between high- and low-elevation ecomorphs of the fire salamander (Salamandra salamandra) that have experienced altitudinal range shifts over the current postglacial period. Strong population structure with high genetic divergence in mitochondrial DNA suggests that vicariant evolution has occurred over several glacial-interglacial cycles and that it has led to cryptic differentiation within ecomorphs. In current parapatric boundaries, we do not find evidence for local extinction and replacement upon postglacial expansion. Instead, parapatric taxa recurrently show discordance between mitochondrial and nuclear markers, suggesting nuclear mediated gene flow across contact zones. Isolation with migration models support this hypothesis by showing significant gene flow across all five parapatric boundaries. Together, our results suggest that, while some genomic regions, such as the mitochondria, may follow morphologic species traits and retreat to isolated mountain tops, other genomic regions, such as nuclear markers, may flow across parapatric boundaries, sometimes leading to a complete genetic merger. We show that despite high ecologic and morphologic divergence over prolonged periods of time, hybridization allows for evolutionary outcomes alternative to extinction and replacement of taxa in response to climate change. PMID- 26850835 TI - Radiology of Osteoporosis. PMID- 26850836 TI - Career expectations and influences among dental students in Malaysia. AB - INTRODUCTION: It is important to understand career expectations of emerging dental graduates if human resources are to be harnessed in support of oral health. The aims of this study were to explore students' career expectations and their perceived influences, and to examine variation according to student and school characteristics. METHODS: All final-year students registered for 2013/2014 across 11 dental schools in Malaysia were invited to participate in a self administered questionnaire (n = 530). The instrument explored short- and long term career expectations, influences and students' background using a mix of open and closed-ended questions. The chi-square test was used for comparison according to student and school characteristics. RESULTS: Three-hundred and fifty six (83%) students, across eight schools, completed the questionnaire. In the short term, undertaking specialist training (46%) was the most commonly cited career goal, and achieving financial stability (79%) was the greatest influence. In the long term, 59% planned to specialise (with a significant difference found according to ethnic group), and 67% considered working full-time, with men significantly more likely to do so than women (P = 0.036). More Malay students (90%) ranked childcare commitments as an important influence on the number of sessions they planned to work per week compared with Chinese students (75%) and Others (74%; P = 0.001). Work-life balance (95%) and high income/financial security (95%) were the main influences on respondents' long-term goals. CONCLUSION: There was a high level of interest in specialisation and a desire to achieve financial stability and work-life balance in the group of dental students who responded to the survey. Long-term career expectations varied according to student but not according to school characteristics. PMID- 26850837 TI - Diurnal testosterone variability is differentially associated with parenting quality in mothers and fathers. AB - Previous studies on the relation between testosterone (T) levels and parenting have found ample evidence for the challenge hypothesis, demonstrating that high T levels inhibit parental involvement and that becoming a parent is related to a decrease in T levels in both mothers and fathers. However, less is known about the relation between T levels and more qualitative aspects of parenting. In the current study we examined basal T levels and diurnal variability in T levels in relation to mothers' and fathers' parenting quality. Participants included 217 fathers and 124 mothers with two children (3 and 5years of age). Evening and morning salivary T samples were analyzed with radio-immunoassays to determine circulating T levels. Parental sensitivity (i.e., child-centered responsiveness) and respect for children's autonomy were observed during free play in the family home. The results showed that higher evening T levels in mothers were associated with more sensitivity to the oldest and youngest child. Diurnal T variability was more consistently associated with parenting behavior towards their children than basal T levels. For fathers, more diurnal variability in T was associated with more sensitivity and more respect for autonomy with their youngest children. For mothers, more diurnal variability in T was associated with less sensitivity to both children and less respect for the youngest child's autonomy. These findings suggest that the T system might act differently in relation to parenting behavior in males and females. PMID- 26850838 TI - Effect of alanine, leucine, and arginine substitution on antimicrobial activity against candida albicans and action mechanism of a cationic octadecapeptide derived from alpha-amylase of rice. AB - AmyI-1-18, an antimicrobial peptide, is a cationic alpha-helical octadecapeptide derived from alpha-amylase of rice (Oryza sativa L. japonica) that contains four cationic amino acid residues (two arginines and two lysines). To enhance the antifungal activity of AmyI-1-18 against Candida albicans, 11 analogs bearing substitutions with alanine, leucine, and/or arginine, which were designed on the basis of the helical wheel projection of AmyI-1-18, were synthesized, and their antifungal activity was investigated. The antifungal activities of four analogs obtained by replacing arginine or lysine with alanine were significantly reduced. The results suggested that the cationic arginine and lysine residues in AmyI-1-18 are important for its antifungal activity. The antifungal activities of two single leucine-substituted analogs were not improved, but among three single arginine-substituted analogs, AmyI-1-18(D15R) had approximately a twofold higher antifungal activity [50% growth-inhibitory concentration (IC50 ): 31 MUM] than AmyI-1-18 (IC50 : 64 MUM) and exhibited low hemolytic activity (4% at 100 MUM). Flow cytometric analysis using propidium iodide revealed that the antifungal activity of AmyI-1-18(D15R) was dependent on its membrane-disrupting activity in a manner different from that of AmyI-1-18. Further enhancement of the cationicity and hydrophobicity of AmyI-1-18(D15R) resulted in no improvement in antifungal activity and a significant increase in hemolytic activity. In this study, the results demonstrated that the antifungal activity of AmyI-1-18 against C. albicans was enhanced through increasing its membrane-disrupting activity by replacing aspartic acid at position 15 with arginine without a significant increase in hemolytic activity. (c) 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 219-229, 2016. PMID- 26850839 TI - Gender differences in disclosure concerns and HIV-related quality of life. AB - HIV-related disclosure concerns are associated with higher rates of concealment and poorer well-being, including poorer health related HIV quality of life (HIV QOL). Little research, however, has examined whether gender differences exist in the links between HIV disclosure concerns and HIV-QOL. We expected that disclosure concerns and gender would be associated with HIV-QOL, such that the relationship between disclosure concerns and poorer HIV-QOL to be stronger in women living with HIV (WLWH) than in men living with HIV (MLWH). One hundred and forty MLWH (n = 102) and WLWH (n = 38) completed an online questionnaire consisting of measures regarding their demographics, disclosure concerns (HIV stigma scale), and HIV-QOL (HIV-AIDS-Targeted Quality of Life Instrument). Results suggested that more disclosure concerns were associated with poorer HIV QOL, but in general, men and women did not differ in their levels of HIV-QOL. As expected, interactions emerged between gender and disclosure concerns such that disclosure concerns were associated with increased health worries and poorer sexual functioning for WLWH but not for MLWH. Interventions should acknowledge the differing needs and experiences of WLWH in order to improve HIV-QOL and increase longevity. PMID- 26850840 TI - Dietary consumption of advanced glycation end products and risk of metabolic syndrome. AB - Metabolic syndrome (MetS) is a complex disorder which has become one of the major public health challenges worldwide. This study was conducted to evaluate the association between dietary advanced glycation end products (AGEs) and risk of MetS and its components. This cross-sectional study was conducted in a representative sample of 5848 adults, aged 19-70 years. Daily consumption of carboxymethyl lysine, a major type of AGEs, was determined using a validated semi quantitative food frequency questionnaire. Across increasing trend of AGEs consumption, the percentage of fat intake increased and that of carbohydrate significantly decreased (p < 0.001). Subjects in the highest (>10,506 kU/d) compared to the lowest (<6673 kU/d) quartile category of AGEs had higher risk of abdominal obesity (OR: 1.19, 95% CI: 1.01-1.39) and hypertriglyceridemia (OR: 1.26, 95% CI: 1.07-1.49). Therefore, recommendation on restriction of AGEs intake could be a practical approach to prevent metabolic abnormalities. PMID- 26850841 TI - c-MYC targets the central oscillator gene Per1 and is regulated by the circadian clock at the post-transcriptional level. AB - Cell proliferation in mammals follows a circadian rhythm while disruption of clock gene expression has been linked to tumorigenesis. Expression of the c-Myc oncogene is frequently deregulated in tumors, facilitating aberrant cell proliferation. c-MYC protein levels display circadian rhythmicity, which is compatible with an in vitro repressive role of the clock-activating complex BMAL1/CLOCK on its promoter. In this report, we provide evidence for the in vivo binding of the core circadian factor BMAL1 on the human c-Myc promoter. In addition, analysis of protein synthesis and degradation rates, as well as post translational acetylation, demonstrate that the clock tightly controls cellular MYC levels. The oncoprotein itself is a transcription factor that by responding to mitogenic signals regulates the expression of several hundred genes. c-MYC driven transcription is generally exerted upon dimerization with MAX and binding to E-box elements, a sequence that is also recognized by the circadian heterodimer. Our reporter assays reveal that the MYC/MAX dimer cannot affect transcription of the circadian gene Per1. However, when overexpressed, c-MYC is able to repress Per1 transactivation by BMAL1/CLOCK via targeting selective E-box sequences. Importantly, upon serum stimulation, MYC was detected in BMAL1 protein complexes. Together, these data demonstrate a novel interaction between MYC and circadian transactivators resulting in reduced clock-driven transcription. Perturbation of Per1 expression by MYC constitutes a plausible alternative explanation for the deregulated expression of clock genes observed in many types of cancer. PMID- 26850842 TI - Quantification of Shunt Volume Through Ventricular Septal Defect by Real-Time 3-D Color Doppler Echocardiography: An in Vitro Study. AB - Quantification of shunt volume is important for ventricular septal defects (VSDs). The aim of the in vitro study described here was to test the feasibility of using real-time 3-D color Doppler echocardiography (RT3-D-CDE) to quantify shunt volume through a modeled VSD. Eight porcine heart phantoms with VSDs ranging in diameter from 3 to 25 mm were studied. Each phantom was passively driven at five different stroke volumes from 30 to 70 mL and two stroke rates, 60 and 120 strokes/min. RT3-D-CDE full volumes were obtained at color Doppler volume rates of 15, 20 and 27 volumes/s. Shunt flow derived from RT3-D-CDE was linearly correlated with pump-driven stroke volume (R = 0.982). RT3-D-CDE-derived shunt volumes from three color Doppler flow rate settings and two stroke rate acquisitions did not differ (p > 0.05). The use of RT3-D-CDE to determine shunt volume though VSDs is feasible. Different color volume rates/heart rates under clinically/physiologically relevant range have no effect on VSD 3-D shunt volume determination. PMID- 26850844 TI - Use of dental adhesives as modeler liquid of resin composites. AB - OBJECTIVES: Resin adhesives (RA) have been applied between resin composite (RC) increments, but there is no consensus on the impact of this technique on the properties of the final restoration. This study evaluated the effect of the presence of RA between RC layers on physical properties, translucency and long term color stability of the restorative material. METHODS: ScotchbondTM Multi Purpose (bond, 3M ESPE) and AdperTM Single Bond 2 (3M ESPE) were used as RA, and FiltekTM Z350 (3M ESPE) as RC. Specimens containing RA were prepared by applying 3 layers of the adhesive between 4 increments of RC; adhesive-free specimens were also used (control). Tests of water sorption and solubility, mechanical performance (microtensile cohesive strength, flexural strength, and flexural modulus, after immediate and long-term water storage), and translucency and color stability (after immediate and 1, 7, 90, and 180 days of water or wine storage) were performed. Scanning electron microscopy (SEM) images were also taken from the fractured specimens (flexural strength test). Data were analyzed using ANOVA and Tukey test (p<0.05). RESULTS: Scotchbond (SBMP) showed lower water sorption and solubility than the control (p<0.001), and an overall similar (p>=0.198, immediate tests) or higher (p<=0.019, long-term tests) mechanical performance. SBMP exhibited a rougher cross-sectional surface compared to the other groups. Translucency remained unaltered after 180 days of storage (p>=0.313), except for single bond that had increased translucency with wine storage (p<0.045). After 180 days, all groups changed color (p<=0.002), although more intensively when immersed in wine. SIGNIFICANCE: The presence of RA within RC increments increased the physical stability of the material, being this effect more evident by using the hydrophobic unfilled adhesive resin (SBMP). This study is the first to show positive results from the use of resin adhesives as modeler liquid of resin composite, which is common in clinical practice. PMID- 26850845 TI - Involvement of the nervous system following experimental infection with Pasteurella multocida B:2 in buffalo (Bubalus bubalis): A clinicopathological study. AB - Haemorrhagic septicaemia (HS) is an acute, fatal, septicaemic disease of cattle and buffaloes caused by one of two specific serotypes of Pasteurella multocida B:2 and E:2 in Asian and African, respectively. It is well known that HS affect mainly the respiratory and digestive tracts. However, involvement of the nervous system in pathogenesis of HS has been reported in previous studies without details. In this study, nine buffalo calves of 8 months old were distributed into three groups. Animals of Group 1 and 2 were inoculated orally and subcutaneously with 10 ml of 1 * 10(12) cfu/ml of P. multocida B:2, respectively, while animals of Group 3 were inoculated orally with 10 ml of phosphate buffer saline as a control. All calves in Group 1 and Group 3 were euthanised after 504 h (21 day) post-infection, while calves in Group 2 had to euthanise after 12 h post infection as they develop sever clinical signs of HS. Significant differences were found in Group 2 in the mean scores of clinical signs, gross and histopathological changes which mainly affect different anatomic regions of the nervous system. In addition, successful bacterial isolation of P. multocida B:2 were obtained from different sites of the nervous system. On the other hand, less sever, clinical, gross and histopathological changes were found in Group 1. These results provide for the first time strong evidence of involving of the nervous system in pathogenesis of HS, especially in the peracute stage of the disease. PMID- 26850846 TI - Quantifying the risk of spread of bovine viral diarrhoea virus (BVDV) between contiguous herds in Ireland. AB - The control of bovine viral diarrhoea virus (BVDV) mainly focuses on the identification and restriction of persistently infected (PI) animals. However, other transmission pathways can also result in new breakdowns, including the movement of animals pregnant with PI calves (Trojan animals) and the spread of infection between contiguous farms. Contiguous spread is likely an important problem in the BVD eradication programme in Ireland, given the spatial distribution of residual infection, and the highly fragmented nature of land holdings on many Irish farms. In this study, we seek to quantify the risk of BVD spread between contiguous herds in Ireland. Multivariable logistic models were used to estimate the risk of a herd having BVD positive calves in January to June 2014 (the study period) when contiguous to a herd that had at least one BVD positive calf born in 2013. The models included risk factors relating to the study herd and to neighbouring herds. Separate multivariable models were built for each of four "PI-neighbour" factors relating to the presence of BVD+ animals and/or the presence of offspring of PI breeding animals. In total, 58,483 study herds were enrolled. The final model contained the province, the log of the number of calf births born during the study period, the number of cattle purchased between January 2013 and January 2014, and with a two-way interaction between the number of animals of unknown BVD status in the study herd and the PI neighbour risk factor. When the number of PI-neighbour herds was used as the PI neighbour risk factor, the odds ratio (OR) associated with the number of PI neighbour herds ranged from 1.07 to 3.02, depending on the number of unknown animals present. To further explore the risk associated with PI-neighbour factors, the models were repeated using a subset of the study herds (n=7440) that contained no animals of unknown status. The best fitting model including "any PI neighbour" as the PI-neighbour factor and also contained the log of the number of calf births born during the study period and the number of cattle purchased. The OR associated with "any PI-neighbour" was 1.92 (95% C.I. 1.37-2.70). This study provides the first quantitative information on the risks posed by the presence of BVD+ animals in neighbouring herds and also highlights the importance of clarifying the BVD status of animals that have not yet been tested in the context of the Irish eradication programme. PMID- 26850847 TI - Tectothalamic inhibitory projection neurons in the avian torus semicircularis. AB - Inhibitory feedforward projection is one of key features of the organization of the central auditory system. In mammals, the inferior colliculus (IC) is the origin of a substantial inhibitory feedforward projection as well as an excitatory projection to the auditory thalamus. This inhibitory feedforward projection is provided by large gamma-aminobutyric acid (GABA)ergic (LG) neurons, which are characterized by their receipt of dense excitatory axosomatic terminals positive for vesicular glutamate transporter (VGLUT) 2. In the avian torus semicircularis (TS), which is the homolog of the IC, neither the homology of cell types nor the presence of inhibitory feedforward inhibition have been established. In this study, we tested the presence of LG neurons in pigeon and chicken by neuroanatomical techniques. The TS contained two types of GABAergic neurons of different soma size. Of these, larger GABA + cells were encircled by dense VGLUT2 + axosomatic terminals. Ultrastructural analyses revealed that more than 30% of the perimeter of a large GABA+, but not small GABA + or GABA-, soma was covered by presumptive excitatory axosomatic terminals, suggesting that large GABA + cells are the sole recipient of dense excitatory axosomatic synapses. After injection of a retrograde tracer into the auditory thalamus, many retrogradely labeled neurons were found bilaterally in the TS, a few of which were GABA+. Almost all tectothalamic GABA + neurons had large somata, and received dense VGLUT2 + axosomatic terminals. These results clearly demonstrated the presence of LG neurons in birds. The similar morphology of LG neurons implies that the function of tectothalamic inhibition is similar among amniotes. J. Comp. Neurol. 524:2604-2622, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26850849 TI - Group IVA phospholipase A(2) deficiency prevents CCl4-induced hepatic cell death through the enhancement of autophagy. AB - Group IVA phospholipase A2 (IVA-PLA2), which generates arachidonate, plays a role in inflammation. IVA-PLA2-deficiency reduced hepatotoxicity and hepatocyte cell death in mice that received a single dose of carbon tetrachloride (CCl4) without any inhibitory effects on CCl4-induced lipid peroxidation. An immunoblot analysis of extracts from wild-type mouse- and IVA-PLA2 KO mouse-derived primary hepatocytes that transiently expressed microtubule-associated protein 1 light chain 3B (LC3) revealed a higher amount of LC3-II, a typical index of autophagosome formation, in IVA-PLA2-deficient cells, suggesting the enhancement of constitutive autophagy. IVA-PLA2 may promote CCl4-induced cell death through the suppression of constitutive autophagy in hepatocytes. PMID- 26850848 TI - Non-invasive glucagon-like peptide-1 receptor imaging in pancreas with (18)F-Al labeled Cys(39)-exendin-4. AB - PURPOSE: Glucagon-like peptide-1 receptor (GLP-1R) is abundantly expressed on beta cells and may be an ideal target for the pancreas imaging. Monitoring the GLP-1R of pancreas could be benefit for understanding the pathophysiology of diabetes. In the present study, (18)F-Al labeled exendin-4 analog, (18)F-Al-NOTA MAL-Cys(39)-exendin-4, was evaluated for PET imaging GLP-1R in the pancreas. METHODS: The targeting of (18)F-Al labeled exendin-4 analog was examined in healthy and streptozotocin induced diabetic rats. Rats were injected with (18)F Al-NOTA-MAL-Cys(39)-exendin-4 and microPET imaging was performed at 1 h postinjection, followed by ex vivo biodistribution. GLP-1R expression in pancreas was determined through post mortern examinations. RESULTS: The pancreas of healthy rats was readily visualized after administration of (18)F-Al-NOTA-MAL Cys(39)-exendin-4, whereas the pancreas of diabetic rats, as well as those from rats co-injected with excess of unlabeled peptides, was barely visible by microPET. At 60 min postinjection, the pancreatic uptakes were 1.02 +/- 0.15%ID/g and 0.23 +/- 0.05%ID/g in healthy and diabetic rats respectively. Under block, the pancreatic uptakes of non-diabetic rats reduced to 0.21 +/- 0.07%ID/g at the same time point. Biodistribution data and IHC staining confirmed the findings of the microPET imaging. CONCLUSION: The favorable preclinical data indicated that (18)F-Al-NOTA-MAL-Cys(39)-exendin-4may be suitable for non-invasive monitoring functional pancreatic beta cells. PMID- 26850850 TI - A natural component from Euphorbia humifusa Willd displays novel, broad-spectrum anti-influenza activity by blocking nuclear export of viral ribonucleoprotein. AB - The need to develop anti-influenza drugs with novel antiviral mechanisms is urgent because of the rapid rate of antigenic mutation and the emergence of drug resistant viruses. We identified a novel anti-influenza molecule by screening 861 plant-derived natural components using a high-throughput image-based assay that measures inhibition of the influenza virus infection. 1,3,4,6-tetra-O-galloyl beta-D-glucopyranoside (TGBG) from Euphorbia humifusa Willd showed broad-spectrum anti-influenza activity against two seasonal influenza A strains, A/California/07/2009 (H1N1) and A/Perth/16/2009 (H3N2), and seasonal influenza B strain B/Florida/04/2006. We investigated the mode of action of TGBG using neuraminidase activity inhibition and time-of-addition assays, which evaluate the viral release and entry steps, respectively. We found that TGBG exhibits a novel antiviral mechanism that differs from the FDA-approved anti-influenza drugs oseltamivir which inhibits viral release, and amantadine which inhibits viral entry. Immunofluorescence assay demonstrated that TGBG significantly inhibits nuclear export of influenza nucleoproteins (NP) during the early stages of infection causing NP to accumulate in the nucleus. In addition, influenza-induced activation of the Akt signaling pathway was suppressed by TGBG in a dose dependent manner. These data suggest that a putative mode of action of TGBG involves inhibition of viral ribonucleoprotein (vRNP) export from the nucleus to the cytoplasm consequently disrupting the assembly of progeny virions. In summary, TGBG has potential as novel anti-influenza therapeutic with a novel mechanism of action. PMID- 26850851 TI - Fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of LncRNA MEG3. AB - There is still no suitable drug for pancreatic cancer treatment, which is one of the most aggressive human tumors. Maternally expressed gene 3 (MEG3), a LncRNA, has been suggested as a tumor suppressor in a range of human tumors. Studies found fenofibrate exerted anti-tumor roles in various human cancer cell lines. However, its role in pancreatic cancer remains unknown. The present study aimed to explore the impacts of fenofibrate on pancreatic cancer cell lines, and to investigate MEG3 role in its anti-tumor mechanisms. We used MTT assay to determine cells proliferation, genome-wide LncRNA microarray analysis to identify differently expressed LncRNAs, siRNA or pCDNA-MEG3 transfection to interfere or upregulate MEG3 expression, western blot to detect protein levels, real-time PCR to determine MEG3 level. Fenofibrate significantly inhibited proliferation of pancreatic cancer cells, increased MEG3 expression and p53 levels. Moreover, knockdown of MEG3 attenuated cytotoxicity induced by fenofibrate. Furthermore, overexpression of MEG3 induced cells death and increased p53 expression. Our results indicated fenofibrate inhibited pancreatic cancer cells proliferation via activation of p53 mediated by upregulation of MEG3. PMID- 26850852 TI - Long non-coding RNA PVT1 and cancer. AB - Genome-wide sequencing technologies have led to the identification of many non coding RNAs and revealed an important role for these molecules in cancer. Although there have been many studies on the role of short non-coding RNAs in cancer, much work remains to characterize the functions of long non-coding RNAs. PVT1, a long non-coding RNA encoded by the human PVT1 gene, is located in the well-known cancer-related region 8q24, also known as the 8q24 'gene desert.' PVT1 has three main molecular mechanisms of action: participating in DNA rearrangements, encoding microRNAs, and interacting with MYC. Studies on the association between PVT1 and cancer have shown that PVT1 is a potential oncogene in a variety of cancer types. However, the underlying molecular mechanisms of PVT1 in cancer remain unknown. Further studies of PVT1 will be required to test the utility of this molecule as a target for cancer diagnosis and therapy, and they should also increase our understanding of the role of long non-coding RNAs in tumorigenesis. PMID- 26850853 TI - Expression and localization of heterogeneous nuclear ribonucleoprotein K in mouse ovaries and preimplantation embryos. AB - Heterogeneous nuclear ribonucleoprotein K (hnRNP K), an evolutionarily conserved protein, is involved in several important cellular processes that are relevant to cell proliferation, differentiation, apoptosis, and cancer development. However, details of hnRNP K expression during mammalian oogenesis and preimplantation embryo development are lacking. The present study investigates the expression and cellular localization of K protein in the mouse ovaries and preimplantation embryos using immunostaining. We demonstrate, for the first time, that hnRNP K is abundantly expressed in the nuclei of mouse oocytes in primordial, primary and secondary follicles. In germ vesicle (GV)-stage oocytes, hnRNP K accumulates in the germinal vesicle in a spot distribution manner. After germinal vesicle breakdown, speckled hnRNP K is diffusely distributed in the cytoplasm. However, after fertilization, the K protein relocates into the female and male pronucleus and persists in the blastomere nuclei. Localization of K protein in the human ovary and ovarian granulosa cell tumor (GCT) was also investigated. Overall, this study provides important morphological evidence to better understand the possible roles of hnRNP K in mammalian oogenesis and early embryo development. PMID- 26850854 TI - Biased alpha-adrenergic receptor and betaarrestin signaling in a cell culture model of benign prostatic hyperplasia. AB - Benign prostatic hyperplasia (BPH) is a common disease in older men that involves the enlargement of the prostate gland. This occurs in response to signal transduction initiated by alpha-adrenergic receptors (alpha-ARs). When bound to ligands, alpha-ARs stimulate the mitogenic extracellular signal-regulated kinases 1 and 2 (ERK) pathway, ultimately promoting stromal and epithelial cell hyperplasia in the prostate. Current knowledge of how alpha-ARs promote prostate cell growth remains incomplete, and despite decades of research, there is no cure for BPH. In this study, we aimed to exploit an in vitro model system of BPH in order to better understand the mechanisms of alpha-AR signaling in prostatic hyperplasia. PMID- 26850855 TI - Validation of the Peel PlateTM AC for Detection of Total Aerobic Bacteria in Dairy and Nondairy Products. AB - Peel PlateTM AC (aerobic count) is a low-profile plastic 47 mm culture dish with adhesive top that contains a dried standard plate count medium with oxidation/reduction indicator triphenyl tetrazolium chloride (TTC) that turns red with dehydrogenase enzyme activity of growing aerobic bacteria. The method provides a conventional quantitative count with simple rehydration and incubation for 48 +/- 3 h at 35 +/- 1 degrees C for most food matrixes and 32 +/- 1 degrees C for 48 +/- 3 h for dairy products. Dairy matrixes claimed and supported with total aerobic count data are whole milk, skim milk, chocolate milk (2% fat), light cream (20% fat), pasteurized whole goat milk, ultra-high temperature pasteurized milk, nonfat dried milk, lactose-reduced milk, strawberry milk, raw cow milk, raw goat milk, raw sheep milk, condensed skim milk, and vanilla ice cream. Food matrixes claimed for aerobic count detection are raw ground beef, environmental sponge of stainless steel, raw ground turkey, dry dog food, liquid whole pasteurized eggs, milk chocolate, poultry carcass rinse, and large animal carcass sponge. The method has been independently evaluated for aerobic count in dairy products: whole milk, skim milk, chocolate milk, and light cream. The method was also independently evaluated for aerobic count in food matrixes: ground beef and sponge rinse from stainless steel surfaces. In the matrix study, each matrix was assessed separately at each contamination level in comparison to an appropriate reference method. Colony counts were determined for each level and then log10-transformed. The transformed data were evaluated for repeatability, mean comparison between methods with 95% confidence interval (CI), and r(2). A CI range of (-0.5, 0.5) on the mean difference was used as the acceptance criterion to establish significant statistical differences between methods. The evaluations demonstrate that the Peel Plate AC provides no statistical differences across most of the matrixes with r(2) > 0.96. In the case of skim milk, there were significant differences that may be explained by a matrix-related stress on the spiked organisms but were not repeated in subsequent experiments. Within method repeatability of Peel Plate AC was similar to reference method with relative standard deviations in the ranges of 2 to 5% when log10 means were >=1.5. Quality control data support that Peel Plate AC is stable for at least 1 year refrigerated. Incubation temperature ranges 30-36 degrees C and times 45 -51 h were not significantly different. PMID- 26850856 TI - Cognitive Deficits in Healthy Elderly Population With "Normal" Scores on the Mini Mental State Examination. AB - This study investigated whether healthy older adults with Mini-Mental State Examination (MMSE) scores above 23 exhibit cognitive impairment on neuropsychological tests. Participants completed the MMSE and a neuropsychological battery including tests of 10 domains. Results were compared to published normative data. On neuropsychological testing, participants performed well on measures of naming and recall but showed mild to moderate impairment in working memory and processing speed and marked impairment in inhibition, sustained attention, and executive functioning. Almost everyone (91%) scored at least 1 standard deviation (SD) below the mean in at least 1 domain. The median number of domains in which individuals scored below 1 SD was 3.0 of 10.0, whereas over 21% scored below 1 SD in 5 domains or more. With the strictest of definitions for impairment, 20% of this population scored below 2.0 SDs below the norm in at least 2 domains, a necessary condition for a diagnosis of dementia. The finding that cognitive impairment, particularly in attention and executive functioning, is found in healthy older persons who perform well on the MMSE has clinical and research implications in terms of emphasizing normal variability in performance and early identification of possible impairment. PMID- 26850857 TI - A new pretest probability score for diagnosis of lower limb deep vein thrombosis in unselected population of outpatients and inpatients. AB - Objective To develop a new pretest probability score for deep vein thrombosis (DVT) in unselected population of outpatients and inpatients. Methods The new score was developed using independent factors from 500 patients clinically suspected of leg DVT. The new score was validated in a second group of 315 patients. Results The score consists of four components: unilateral leg pain, confinement to bed, calf enlargement >3 cm compared with the other side, and previous venous thromboembolism. A score >=2 indicated a high probability while a score <2 indicated low probability. The sensitivity and specificity of the new score were 71.60% and 79.49%, respectively. The area under the receiver operating characteristic curve for the new score was 0.79. The combination of a new score <2 and D-dimer level <500 ug/L had a negative predictive value of 96.43%. Conclusions Our new score was valid in an unselected population of outpatients and inpatients. PMID- 26850858 TI - Oil, Earth mass and gravitational force. AB - Fossil fuels are intensively extracted from around the world faster than they are renewed. Regardless of direct and indirect effects of such extractions on climate change and biosphere, another issue relating to Earth's internal structure and Earth mass should receive at least some interest. According to the Energy Information Administration (EIA), about 34 billion barrels of oil (~4.7 trillion metric tons) and 9 billion tons of coal have been extracted in 2014 worldwide. Converting the amounts of oil and coal extracted over the last 3 decades and their respective reserves, intended to be extracted in the future, into mass values suggests that about 355 trillion tons, or ~5.86*10(-9) (~0.0000000058)% of the Earth mass, would be 'lost'. Although this is a tiny percentage, modeling the potential loss of Earth mass may help figuring out a critical threshold of mass loss that should not be exceeded. Here, I briefly discuss whether such loss would have any potential consequences on the Earth's internal structure and on its gravitational force based on the Newton's law of gravitation that links the attraction force between planets to their respective masses and the distance that separate them. PMID- 26850859 TI - Temporal variability of micro-organic contaminants in lowland chalk catchments: New insights into contaminant sources and hydrological processes. AB - This paper explores the temporal variation of a broad suite of micro organic (MO) compounds within hydrologically linked compartments of a lowland Chalk catchment, the most important drinking water aquifer in the UK. It presents an assessment of results from relatively high frequency monitoring at a well-characterised site, including the type and concentrations of compounds detected and how they change under different hydrological conditions including exceptionally high groundwater levels and river flow conditions during 2014 and subsequent recovery. This study shows for the first time that within the Chalk groundwater there can be a greater diversity of the MOs compared to surface waters. Within the Chalk 26 different compounds were detected over the duration of the study compared to 17 in the surface water. Plasticisers (0.06-39MUg/L) were found to dominate in the Chalk groundwater on 5 visits (38.4%) accounting for 14.5% of detections but contributing highest concentrations whilst other compounds dominated in the surface water. Trichloroethene and atrazine were among the most frequently detected compounds. The limit for the total pesticide concentration detected did not exceed EU/UK prescribed concentration values for drinking water. Emerging organic compounds such as caffeine, which currently do not have water quality limits, were also detected. The low numbers of compounds found within the hyporheic zone highlight the role of this transient interface in the attenuation and breakdown of the MOs, and provision of an important ecosystem service. PMID- 26850860 TI - Acidic sandy soil improvement with biochar - A microcosm study. AB - Biochar produced from a wide range of organic materials by pyrolysis has been reported as a means to improve soil physical properties, fertility and crop productivity. However, there is a lack of studies on the complex effects of biochar both on the degraded sandy soil physico-chemical properties and the soil biota as well as on toxicity, particularly in combined application with fertilizer and compost. A 7-week microcosm experiment was conducted to improve the quality of an acidic sandy soil combining variations in biochar types and amounts, compost and fertilizer application rates. The applied biochars were produced from different feedstocks such as grain husks, paper fibre sludge and wood screenings. The main purpose of the microcosm experiment was to assess the efficiency and applicability of different biochars as soil amendment prior to field trials and to choose the most efficient biochar to improve the fertility, biological activity and physical properties of acidic sandy soils. We complemented the methodology with ecotoxicity assessment to evaluate the possible risks to the soil as habitat for microbes, plants and animals. There was clear evidence of biochar-soil interactions positively affecting both the physico chemical properties of the tested acidic sandy soil and the soil biota. Our results suggest that the grain husk and the paper fibre sludge biochars applied to the tested soil at 1% and 0.5 w/w% rate mixed with compost, respectively can supply a more liveable habitat for plants and soil living animals than the acidic sandy soil without treatment. PMID- 26850861 TI - Combined nano-biotechnology for in-situ remediation of mixed contamination of groundwater by hexavalent chromium and chlorinated solvents. AB - The present report describes a 13month pilot remediation study that consists of a combination of Cr(VI) (4.4 to 57mg/l) geofixation and dechlorination of chlorinated ethenes (400 to 6526MUg/l), achieved by the sequential use of nanoscale zerovalent iron (nZVI) particles and in situ biotic reduction supported by whey injection. The remediation process was monitored using numerous techniques, including physical-chemical analyses and molecular biology approaches which enabled both the characterization of the mechanisms involved in pollutant transformation and the description of the overall background processes of the treatment. The results revealed that nZVI was efficient toward Cr(VI) by itself and completely removed it from the groundwater (LOQ 0.05mg/l) and the subsequent application of whey resulted in a high removal of chlorinated ethenes (97 to 99%). The persistence of the reducing conditions, even after the depletion of the organic substrates, indicated a complementarity between nZVI and the whey phases in the combined technology as the subsequent application of whey phase partially assisted the microbial regeneration of the spent nZVI by promoting its reduction into Fe(II), which further supported remediation conditions at the site. Illumina sequencing and the detection of functional vcrA and bvcA genes documented a development in the reducing microbes (iron-reducing, sulfate-reducing and chlororespiring bacteria) that benefited under the conditions of the site and that was probably responsible for the high dechlorination and/or Cr(VI) reduction. The results of this study demonstrate the feasibility and high efficiency of the combined nano-biotechnological approach of nZVI and whey application in-situ for the removal of Cr(VI) and chlorinated ethenes from the groundwater of the contaminated site. PMID- 26850862 TI - Effects of positive blood alcohol concentration on outcome and systemic interleukin-6 in major trauma patients. AB - BACKGROUND: The influence of alcohol on the outcome after major trauma remains controversial. In several recent studies, alcohol has been associated with neuroprotective effects in head injuries, while others reported negative or no effects on survival and/or the in-hospital stay in major trauma patients (TP). The purpose of this study was to examine the relationship of alcohol with injury characteristics and outcome as well as to analyze possible anti-inflammatory properties in major TP. PATIENTS/METHODS: 184 severely injured TP with an Injury Severity Score (ISS) >=16 were successively enrolled. All patients had measured blood alcohol concentration (BAC). Patients were grouped according to their positive BAC (>0.50/00, BAC) vs. <0.50/00 alcohol (no BAC) upon arrival at the emergency department (ED). Injury characteristics, physiologic parameters and outcome with respect to organ or multiple organ failure (MOF), SIRS, sepsis, pneumonia, ARDS or mortality were assessed. Systemic levels of interleukin (IL)-6 at ED were determined. RESULTS: Forty-nine TP had positive BAC without chronic alcohol abuse history and 135 patients had BAC levels below 0.50/00. Overall injury severity and age were comparable in both groups. No BAC TP received significantly higher numbers of packed red blood cells and fresh frozen plasma (transfused within the initial 24h or in total) compared to BAC TP. Organ failure, MOF, SIRS, sepsis, pneumonia, ARDS and the in-hospital mortality were not different between both groups. Trauma patients with positive BAC had significantly decreased leukocyte numbers and systemic IL-6 levels compared to no BAC group. There was a significant positive correlation between leukocyte counts and IL-6 as well as BAC and leukocytes. BAC levels did not correlate with IL-6. CONCLUSIONS: Positive BAC is associated with reduced leukocyte numbers and lowered systemic IL-6 levels at admittance indicating immune-suppressive effects of alcohol in major trauma patients. PMID- 26850863 TI - CFD of mixing of multi-phase flow in a bioreactor using population balance model. AB - Mixing in bioreactors is known to be crucial for achieving efficient mass and heat transfer, both of which thereby impact not only growth of cells but also product quality. In a typical bioreactor, the rate of transport of oxygen from air is the limiting factor. While higher impeller speeds can enhance mixing, they can also cause severe cell damage. Hence, it is crucial to understand the hydrodynamics in a bioreactor to achieve optimal performance. This article presents a novel approach involving use of computational fluid dynamics (CFD) to model the hydrodynamics of an aerated stirred bioreactor for production of a monoclonal antibody therapeutic via mammalian cell culture. This is achieved by estimating the volume averaged mass transfer coefficient (kL a) under varying conditions of the process parameters. The process parameters that have been examined include the impeller rotational speed and the flow rate of the incoming gas through the sparger inlet. To undermine the two-phase flow and turbulence, an Eulerian-Eulerian multiphase model and k-epsilon turbulence model have been used, respectively. These have further been coupled with population balance model to incorporate the various interphase interactions that lead to coalescence and breakage of bubbles. We have successfully demonstrated the utility of CFD as a tool to predict size distribution of bubbles as a function of process parameters and an efficient approach for obtaining optimized mixing conditions in the reactor. The proposed approach is significantly time and resource efficient when compared to the hit and trial, all experimental approach that is presently used. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:613-628, 2016. PMID- 26850864 TI - [Bridging the Digital Divide]. PMID- 26850865 TI - Mechanics of biological membranes. PMID- 26850866 TI - Is Intra-Socket Drug Delivery Appropriate? PMID- 26850867 TI - Unusual Presentation of Epstein-Barr Virus-Positive Diffuse Large B-Cell Non Hodgkin Lymphoma of the Elderly. AB - This report describes the case of a 76-year-old woman diagnosed with Epstein-Barr virus-positive diffuse large B-cell non-Hodgkin lymphoma of the elderly. She had an unusual presentation of the disease with widespread skeletal muscle, masticatory muscle, and parotid gland involvement and the development of interesting erythematous lesions in the neck during chemotherapy. One month after completion of chemotherapy, positron-emission tomography (PET) showed features of persistent lymphoma, but a repeat PET scan a month later showed no active disease. This case reiterates 2 important points: first, to consider lymphoma a differential diagnosis in masticatory muscle enlargement and second, to question false positivity when interpreting post-treatment PET scan results, especially in the absence of clinical disease. PMID- 26850868 TI - Sialendoscopy of Salivary Glands Affected by Sjogren Syndrome: A Randomized Controlled Pilot Study. AB - PURPOSE: Sialendoscopy of the major salivary glands could alleviate the oral symptoms of Sjogren syndrome (SS) and restore salivary function. The aim of this pilot study was to evaluate the effect of sialendoscopy of the major salivary glands on salivary flow, saliva composition, and mouthfeel in patients with SS and to collect data for sample size analysis for a larger clinical trial. MATERIALS AND METHODS: Twenty patients diagnosed with SS were randomly assigned to a nonintervention control group or a sialendoscopy group. Unstimulated whole saliva flow, stimulated whole saliva flow, Clinical Oral Dryness Score, Xerostomia Inventory score, and EULAR Sjogren's Syndrome Patient Reported Index score were obtained 1 week before (T0), 1 week after (T2), and 8 weeks after (T3) sialendoscopy. Unstimulated whole saliva was analyzed for amylase concentration, activity, and mucin 5B concentration. Amylase and mucin 5B output were calculated. RESULTS: In the sialendoscopy group, unstimulated and stimulated whole saliva flows were numerically higher at T2 and T3 compared with T0. Xerostomia Inventory score was significantly lower in the sialendoscopy group at T2 compared with T0 (P = .03). Unstimulated and stimulated whole saliva flows were higher in the sialendoscopy group compared with the control group at T2 and T3 (not meaningful). Significant differences were found between groups for the EULAR Sjogren's Syndrome Patient Reported Index score at T2 (P = .03) and T3 (P = .001). Xerostomia Inventory score and Clinical Oral Dryness Score in the sialendoscopy group were lower compared with the control group at T2 (P = .02) and at T3 (P = .04), indicating less oral dryness. CONCLUSION: This pilot study indicates a positive effect of sialendoscopy on some parameters, but it cannot yet be concluded that it has a positive effect on salivary flow in patients with SS. These preliminary results need to be verified in a randomized controlled trial with a larger sample and longer follow-up period. PMID- 26850870 TI - A Management Strategy for Idiopathic Bone Cavities of the Jaws. AB - PURPOSE: Idiopathic bone cavities (IBCs) are benign osseous pseudocysts of unclear etiology. Their clinical course and response to treatment are poorly understood. The purpose of this study was to present a case series of patients with IBC with long-term follow-up. PATIENTS AND METHODS: A retrospective case series of patients with IBC of the jaw was implemented. Medical records were reviewed for data on presentation and imaging. All patients underwent surgical exploration to confirm the diagnosis. Follow-up radiographs were evaluated for resolution or persistence after the procedure. Descriptive data were summarized. RESULTS: The sample included 45 patients (60% girls) with 47 IBCs who presented at a mean age of 13.5 +/- 0.35 years (range, 9 to 17 yr). All lesions were asymptomatic and discovered as incidental findings; the average size was 2.0 cm (range, 0.8 to 7 cm). Most (n = 44) were solitary lesions of the mandible presenting within the body (n = 27), symphysis (n = 15), or ramus (n = 2). One patient had synchronous bilateral mandibular and maxillary IBCs. Common radiographic features included scalloping without root resorption or displacement and cortical thinning without expansion or perforation. Intraoperative findings showed an empty bone cavity often filled with blood-tinged serous fluid or blood. The histopathology of scrapings from the bony wall showed benign mixed fibrous tissue and no epithelial lining. Average radiographic follow-up was 32.7 +/- 6.7 months (range, 0 to 9 yr). After exploration and curettage, 43% of patients had complete bone fill within 2 to 5 years. The other 57% had no change in lesion size at an average of 2.25 years (range, 2 to 9 yr). No patients developed symptoms, had enlargement of the lesion, or had pathologic fracture. CONCLUSION: Many IBCs persist for years despite exploration and curettage. Nonetheless, unresolved lesions did not enlarge or cause harm. A single procedure to confirm the diagnosis is sufficient for management. PMID- 26850869 TI - Oral Trauma and Tooth Avulsion Following Explosion of E-Cigarette. AB - Electronic cigarettes (E-cigarettes), or personal vaporizers, were introduced in 2003 and have been available in the United States since 2007. In addition to the health and safety concerns of the aerosol delivery of nicotine through E cigarettes, during the past 8 years, reports of explosions and fires caused by the E-cigarette devices have led the US Fire Administration to evaluate the safety of these devices. These explosions have been observed frequently enough that the US Department of Transportation has recently banned E-cigarette devices in checked baggage aboard airplanes. This report contributes to existing knowledge about the hazards related to E-cigarettes by describing oral hard and soft tissue injuries from an E-cigarette explosion. PMID- 26850871 TI - Selective Versus Comprehensive Neck Dissection in Patients With T1 and T2 Oral Squamous Cell Carcinoma and cN0pN(+) Neck. AB - PURPOSE: There is still no consensus on the oncologic safety of selective neck dissection (SND) in the management of pathologically positive neck in patients with oral squamous cell carcinoma (OSCC). This study compared the clinical outcome between SND and comprehensive neck dissection (CND) for patients with T1 and T2 OSCC and a clinically negative but pathologically positive neck. MATERIALS AND METHODS: Retrospective study of medical records of patients with T1 and T2 OSCC and clinical N0 but pathologic N(+) disease from March 2000 through March 2011 was performed. Thirty-seven patients underwent SND or CND. Median follow-up was 51 months. Regional control and disease-specific survival rates were statistically analyzed. RESULTS: No significant differences in 3-year ipsilateral neck control rate (81.8 vs 91.7%; P = .590 by log-rank test) and overall regional control rate (72.7 vs 86.8%; P = .424 by log-rank test) were found between the SND and CND groups. Three-year disease-specific survival rates of the SND and CND groups were 72.7 and 82.1%, respectively. No significant difference was found between these 2 groups by log-rank test (P = .428). CONCLUSIONS: The results indicate that SND in conjunction with postoperative radiotherapy is effective in the management of patients with T1 and T2 OSCC and cN0pN(+) neck. PMID- 26850872 TI - Modified Mandibular Inferior Border Sagittal Split Osteotomy Reduces Postoperative Risk for Developing Inferior Border Defects. AB - PURPOSE: The purpose of this study was to evaluate the impact of a modified sagittal split osteotomy (SSO) surgical technique on the incidence of persisting inferior border defects. The secondary aim was to identify risk factors associated with the development of these complications. MATERIALS AND METHODS: The patient charts and radiographs of 276 consecutive patients who underwent bilateral SSO, performed by a single surgeon in 2 different centers from July 2012 to September 2014, were retrospectively examined. The predictor variable was length of advancement. The outcome variable was the presence or absence of an inferior border defect. Other variables included age and side of the jaw. In all cases the same surgical technique was used. All statistical analyses were performed using SAS software, version 9.4 (SAS Institute, Cary, NC). RESULTS: The analysis included 408 operation sites in 204 patients (132 female and 72 male patients; median age, 22 years; age range, 13 to 66 years). In 5.1% of operation sites an osseous defect at the lower border of the mandible was observed. Age at the time of surgery (P < .0001) and length of advancement (P = .0111) were identified as risk factors for the development of a persisting osseous defect at the inferior border of the osteotomy gap after SSO. CONCLUSIONS: This study confirms the findings previously reported by our research group that the modified inferior border osteotomy technique in SSO results in a substantial lower frequency of persisting inferior border defects. Surgeons are advised to ensure that the lingual cortex of the inferior border is not included in the split during mandibular advancements, and in cases in which the advancement is more than 10 mm and/or the patient is older than 30 years, surgeons might want to consider using a bone graft or a bone graft substitute. PMID- 26850873 TI - Pharyngeal Flap Is Effective Treatment for Post Maxillary Advancement Velopharyngeal Insufficiency in Patients With Repaired Cleft Lip and Palate. AB - PURPOSE: Patients with repaired cleft lip and cleft palate (CL/P) can develop velopharyngeal insufficiency (VPI) after Le Fort I maxillary advancement. The aim of this study was to evaluate speech outcomes in patients who required a pharyngeal flap after Le Fort I maxillary advancement. PATIENTS AND METHODS: This retrospective cohort study included all patients with repaired CL/P who underwent a Le Fort I osteotomy and subsequently required a pharyngeal flap to correct VPI. Patients were included if they had outcome measurements documented at 3 time points: 1) before Le Fort I (baseline), 2) after Le Fort I, and 3) after pharyngeal flap. Outcome measurements, including speech characteristics (resonance, nasal emission, and intraoral pressure) and velopharyngeal function, were evaluated on perceptual assessment by a speech pathologist specializing in cleft care. Velopharyngeal closure was assessed with multi-view videofluoroscopy or nasopharyngoscopy. Patient characteristics and descriptive statistics were summarized and continuous data were expressed as mean +/- standard deviation. Repeated-measures analysis of variance and paired samples t test were used to measure changes in speech outcome variables between time points. All P values were 2-tailed and considered significant for values less than .05. RESULTS: There were 23 patients for analysis (13 girls [56.5%] and 10 boys [43.5%]). Two patients (9%) had cleft palate only, 9 (39%) had unilateral cleft lip and palate (CLP), and 12 (52%) had bilateral CLP. Follow-up evaluations performed on average 12 months postoperatively showed statistically meaningful improvement for all variables, including decreased hypernasality, reduced nasal emission, and increased intraoral pressure for consonant production. Patients with repaired CL/P who had VPI after Le Fort I maxillary advancement showed significant improvement in all outcome measurements after pharyngeal flap (P < .001). CONCLUSIONS: The superiorly based pharyngeal flap is highly successful in correcting VPI after Le Fort I maxillary advancement in patients with repaired CL/P. PMID- 26850874 TI - Interpersonal Violence Is Associated With Increased Severity of Geriatric Facial Trauma. AB - PURPOSE: The geriatric population is rapidly increasing in number with increased demand on health care resources including those spent on the treatment of maxillofacial trauma. The purpose of this analysis was to investigate the independent and cumulative associations between potential risk factors (age, gender, mechanism of injury, drug use, and alcohol use) for and the severity of geriatric facial trauma. METHODS: This was a cross-sectional analysis of secondary data of geriatric (individuals aged >=65 years) facial trauma using the Allegheny General Hospital Trauma Registry database. Data were collected for diagnosis codes that reflected facial trauma (International Classification of Diseases, Ninth Revision codes 802.0 to 802.9, 800.1 to 801.9, and 803.0 to 804.9) and specific mechanisms of injury (E810 to E819, motor vehicle traffic accidents; E880 to E888, accidental falls; and E960 to E969, injury purposely inflicted by other persons). The Facial Injury Severity Scale (FISS) is a validated measurement that was used to determine the severity of the facial trauma and calculated through analysis of the abstracted data obtained from the trauma registry and patient records. Pearson correlations, 2-way independent t test, 1-way analysis of variance, and multiple linear regression were used to test hypotheses for independent and cumulative associations between the risk factors for and the severity of geriatric facial trauma. Statistical significance was set at the P < .05 level. RESULTS: The sample was composed of 229 patients with a mean age of 72.3 +/- 4.5 years. A statistically significant association between mechanism of injury and the severity of geriatric facial trauma (P = .019) was found. Specifically, interpersonal violence (assault) was associated with the greatest facial trauma severity (FISS score, 4.2) when compared with motor vehicle collisions (FISS score, 2.2; P = .011) and falls (FISS score, 2.4; P = .016). CONCLUSIONS: Interpersonal violence (assault) is associated with increased severity of geriatric facial trauma compared with other risk factors. PMID- 26850875 TI - Use of Computer-Assisted Navigation in the Retrieval of Accidentally Displaced Third Molars. AB - PURPOSE: The purpose of this study was to describe the application of computer assisted navigation for the retrieval of accidentally displaced mandibular third molars. PATIENTS AND METHODS: All patients identified as having an accidentally displaced mandibular third molar or root fragment and presented to the authors' department from April 2013 through June 2015 were included in this prospective study. Retrieval of the displaced molar was performed in these patients under the guidance of computer-assisted navigation, in which a registered forceps was used to clamp and retrieve the molar. Postoperative complications were assessed for all patients. RESULTS: Twelve patients were included in this case series. Using computer-assisted navigation, the operation proceeded successfully in all patients. These patients displayed uneventful healing without postoperative complications. CONCLUSION: Computer-assisted navigation is a safe, straightforward, and minimally invasive treatment method that can be applied for the retrieval of accidentally displaced third molars. It is recommended as an intraoperative tool for the retrieval of teeth or tooth fragments displaced into areas that are difficult to access. PMID- 26850876 TI - Effect of p38 Mitogen Activated Protein Kinase Inhibitor on Temporomandibular Joint Synovitis Induced by Occlusal Alteration. AB - PURPOSE: To investigate the alteration in rat temporomandibular joint (TMJ) synovial membrane induced by increased occlusal vertical dimension (iOVD) and to determine whether the p38 mitogen activated protein kinase (MAPK) signaling cascade is involved. MATERIALS AND METHODS: Thirty-six rats were randomly divided into 3 groups: control + normal saline (NS; controls), iOVD + NS, and iOVD + SB203580 (a potent p38 MAPK inhibitor). Morphologic changes of synovial tissues were observed and scored. Activation levels of p38 MAPK and activating transcription factor-2 (ATF2) were detected by immunohistochemistry. Expression levels of interleukin-1beta (IL-1beta) and matrix metalloproteinase-3 (MMP-3) were measured by quantitative real-time polymerase chain reaction and immunohistochemistry. RESULTS: Obvious synovitis was found in the iOVD group. P38 and ATF2 were activated, and mRNA and protein expression levels of IL-1beta and MMP-3 were upregulated after iOVD. However, decreased synovial tissue inflammation and lower mRNA and protein levels of IL-1beta and MMP-3 were observed in the iOVD + SB203580 group. CONCLUSION: iOVD can induce temporomandibular joint synovitis, and the p38 MAPK signaling cascade might participate in and aggravate the process of articular inflammation. PMID- 26850877 TI - Sedation Protocol Using Dexmedetomidine for Third Molar Extraction. AB - PURPOSE: The aim of this study was to establish a proper sedative protocol of dexmedetomidine for outpatients. MATERIALS AND METHODS: The study compared compare patients' pain, satisfaction, adverse events, and sedation depth during extraction of third molars using a sedative protocol of intravenous (IV; 1.0 MUg/kg) versus intranasal (IN; 1.5 MUg/kg) administration of dexmedetomidine. In total, 240 patients were randomized, 160 patients received dexmedetomidine, and data, including the amount of agent used, visual analog scale (VAS) pain score, adverse events, VAS score of patient satisfaction, and bispectral index, were recorded. RESULTS: Patients in the dexmedetomidine groups reported lower VAS pain scores and higher VAS satisfaction scores than patients in the local anesthesia group. There were no statistically meaningful differences between dexmedetomidine groups. Sedation with the IV route was slightly deeper than with the IN route. However, there were no statistically meaningful differences. CONCLUSION: IN or IV administration of dexmedetomidine is recommended as an effective, safe, and competent protocol in outpatient sedative surgeries. PMID- 26850878 TI - Copy number variation of a gene cluster encoding endopolygalacturonase mediates flesh texture and stone adhesion in peach. AB - Texture is an important attribute affecting consumer perception of fruit quality. Peach melting flesh and flesh adhesion to stone (endocarp) are simply inherited and controlled by the F-M locus on linkage group (LG) 4. Here, we report that two genes encoding endopolygalacturonase (endoPG) in the F-M locus, designated PpendoPGF and PpendoPGM, are associated with the melting flesh and stone adhesion traits. PpendoPGM controls melting flesh while PpendoPGF has pleiotropic effects on both melting flesh and stone adhesion. The F-M locus has three allelic copy number variants of endoPG, H1 (PpendoPGF and PpendoPGM), H2 (PpendoPGM), and H3 (null). The H2 haplotype represents the ancestral one while the H1 and H3 haplotypes are two variants due to duplication and deletion of PpendoPGM, respectively. Accessions with H1H1, H1H2, or H1H3 genotypes show the freestone or semi-freestone and melting flesh phenotype, while both H2H2 and H2H3 accessions have the clingstone and melting flesh phenotype. The H3H3 accessions have the clingstone and non-melting flesh phenotype. Our study not only demonstrates a driving role of gene copy number variations in flesh texture diversification in fruit trees, but also provides a useful diagnostic tool for early seedling selection in peach breeding programmes. PMID- 26850879 TI - Cellular and molecular insight into the inhibition of primary root growth of Arabidopsis induced by peptaibols, a class of linear peptide antibiotics mainly produced by Trichoderma spp. AB - Trichoderma spp. are well known biocontrol agents that produce a variety of antibiotics. Peptaibols are a class of linear peptide antibiotics mainly produced by Trichoderma Alamethicin, the most studied peptaibol, is reported as toxic to plants at certain concentrations, while the mechanisms involved are unclear. We illustrated the toxic mechanisms of peptaibols by studying the growth-inhibitory effect of Trichokonin VI (TK VI), a peptaibol from Trichoderma longibrachiatum SMF2, on Arabidopsis primary roots. TK VI inhibited root growth by suppressing cell division and cell elongation, and disrupting root stem cell niche maintenance. TK VI increased auxin content and disrupted auxin response gradients in root tips. Further, we screened the Arabidopsis TK VI-resistant mutant tkr1. tkr1 harbors a point mutation in GORK, which encodes gated outwardly rectifying K(+)channel proteins. This mutation alleviated TK VI-induced suppression of K(+)efflux in roots, thereby stabilizing the auxin gradient. The tkr1 mutant also resisted the phytotoxicity of alamethicin. Our results indicate that GORK channels play a key role in peptaibol-plant interaction and that there is an inter-relationship between GORK channels and maintenance of auxin homeostasis. The cellular and molecular insight into the peptaibol-induced inhibition of plant root growth advances our understanding of Trichoderma-plant interactions. PMID- 26850880 TI - Characterizing the Molecular Pathology of Arrhythmogenic Cardiomyopathy in Patient Buccal Mucosa Cells. AB - BACKGROUND: Analysis of myocardium has revealed mechanistic insights into arrhythmogenic cardiomyopathy but cardiac samples are difficult to obtain from probands and especially from family members. To identify a potential surrogate tissue, we characterized buccal mucosa cells. METHODS AND RESULTS: Buccal cells from patients, mutation carriers, and controls were immunostained and analyzed in a blinded fashion. In additional studies, buccal cells were grown in vitro and incubated with SB216763. Immunoreactive signals for the desmosomal protein plakoglobin and the major cardiac gap junction protein Cx43 were markedly diminished in buccal mucosa cells from arrhythmogenic cardiomyopathy patients with known desmosomal mutations when compared with controls. Plakoglobin and Cx43 signals were also reduced in most family members who carried disease alleles but showed no evidence of heart disease. Signal for the desmosomal protein plakophilin-1 was reduced in buccal mucosa cells in patients with PKP2 mutations but not in those with mutations in other desmosomal genes. Signal for the desmosomal protein desmoplakin was reduced in buccal mucosa cells from patients with mutations in DSP, DSG2, or DSC2 but not in PKP2 or JUP. Abnormal protein distributions were reversed in cultured cells incubated with SB216763, a small molecule that rescues the disease phenotype in cardiac myocytes. CONCLUSIONS: Buccal mucosa cells from arrhythmogenic cardiomyopathy patients exhibit changes in the distribution of cell junction proteins similar to those seen in the heart. These cells may prove useful in future studies of disease mechanisms and drug screens for effective therapies in arrhythmogenic cardiomyopathy. PMID- 26850881 TI - Safety and Feasibility of a Minimally Fluoroscopic Approach for Ventricular Tachycardia Ablation in Patients With Structural Heart Disease: Influence of the Ventricular Tachycardia Substrate. AB - BACKGROUND: We sought to evaluate the safety and feasibility of a minimally fluoroscopic approach using the CARTOUNIVU module during scar-related ventricular tachycardia (VT) ablation. METHODS AND RESULTS: Consecutive patients with structural heart disease undergoing VT ablation using the CARTOUNIVU module were prospectively included and classified depending on their VT substrate: (1) ischemic VT (IVT) and (2) nonischemic VT and depending on the presence of an epicardial access. Radiation exposure parameters and major and minor procedure related complications were registered. A near-zero fluoroscopy exposure was defined as those procedures with an effective dose <=1 mSv. A total of 44 VT ablation procedures were performed in 41 patients (22 IVT and 19 nonischemic VT). The use of the CARTOUNIVU module resulted in low levels of radiation exposure: median total fluoroscopy time and effective dose of 6.08 (1.51-12.36) minutes and 2.15 (0.58-8.22) mSv, respectively. Patients with IVT had lower radiation exposure than patients with nonischemic VT (total fluoroscopy time, 2.53 [1.22 11.22] versus 8.51 [5.55-17.34] minutes; P=0.016). Epicardial access was associated with significantly higher levels of radiation exposure. Complications occurred in 4.9% patients, none of them being related to the use of the image integration tool. A near-zero fluoroscopy ablation could be performed in 14 of 44 procedures (32%), 43% of IVT procedures, and 50% of procedures with endocardial access only. CONCLUSIONS: The use of the CARTOUNIVU module during scar-related VT ablation resulted in low levels of radiation exposure. A near-zero fluoroscopy approach can be achieved in up to half of the procedures, especially in IVT patients with endocardial ablation. PMID- 26850882 TI - Loss of the histone chaperone ASF1B reduces female reproductive capacity in mice. AB - Anti-silencing function 1 (ASF1) is an evolutionarily conserved histone H3-H4 chaperone involved in the assembly/disassembly of nucleosome and histone modification. Two paralogous genes, Asf1a and Asf1b, exist in the mouse genome. Asf1a is ubiquitously expressed and its loss causes embryonic lethality. Conversely, Asf1b expression is more restricted and has been less studied. To determine the in vivo function of Asf1b, we generated a Asf1b-deficient mouse line (Asf1b(GT(ROSA-betageo)437)) in which expression of the lacZ reporter gene is driven by the Asf1b promoter. Analysis of beta-galactosidase activity at early embryonic stages indicated a correlation between Asf1b expression and cell differentiation potential. In the gonads of both male and female, Asf1b expression was specifically detected in the germ cell lineage with a peak expression correlated with meiosis. The viability of Asf1b-null mice suggests that Asf1b is dispensable for mouse development. However, these mice showed reduced reproductive capacity compared with wild-type controls. We present evidence that the timing of meiotic entry and the subsequent gonad development are affected more severely in Asf1b-null female mice than in male mice. In female mice, in addition to subfertility related to altered gamete formation, variable defects compromising the development and/or survival of their offspring were also observed. Altogether, our data indicate the importance of Asf1b expression at the time of meiotic entry, suggesting that chromatin modifications may play a central role in this process. PMID- 26850884 TI - Cyclic stretch enhances apoptosis in human lumbar ligamentum flavum cells via the induction of reactive oxygen species generation. AB - OBJECTIVE: The lumbar ligamentum flavum (LF) is an important part of the spine to maintain the stability of the spine. In this study we aimed to examine whether mechanical force by cyclic stretch could induce apoptosis in human LF cells and investigate the underlying mechanism. METHODS: LF cells were isolated from six young patients undergoing spinal surgery and then cultured in vitro. LF cells were subjected to cyclic stretch and the poptosis was detected by flow cytometry. The level of intracellular reactive oxygen species (ROS) and caspase-9 activity were measured. RESULTS: Cyclic stretch at a frequency of 0.5 Hz with 20% elongation induced the apoptosis of human LF cells in vitro, and this was correlated with increased ROS generation and activation of caspase-9. CONCLUSION: Our study suggests that cyclic stretch-induced apoptosis in human LF cells may be mediated by ROS generation and the activation of caspase-9. PMID- 26850886 TI - [Emphasis on percutaneous transthoracic lung biopsy in the diagnosis of pulmonary lesions]. PMID- 26850887 TI - [Perioperative management of bronchial thermolpasty for asthma]. PMID- 26850885 TI - Comparison of alfaxalone, ketamine and thiopental for anaesthetic induction and recovery in Thoroughbred horses premedicated with medetomidine and midazolam. AB - REASONS FOR PERFORMING STUDY: There is limited information on clinical use of the new injectable anaesthetic agent alfaxalone in Thoroughbred horses. OBJECTIVES: To compare anaesthetic induction and recovery characteristics and cardiopulmonary responses between alfaxalone, ketamine and thiopental in Thoroughbred horses premedicated with medetomidine and midazolam. STUDY DESIGN: Randomised blinded experimental cross-over study. METHODS: Six Thoroughbred horses were anaesthetised 3 times with alfaxalone 1 mg/kg bwt, ketamine 2.5 mg/kg bwt or thiopental 4 mg/kg bwt after premedication with medetomidine 6 MUg/kg bwt and midazolam 20 MUg/kg bwt. Qualities of anaesthetic induction and recovery were scored on a scale of 1 (poor) to 5 (excellent). Induction time and recovery time were recorded. Cardiopulmonary values (heart rate, respiratory rate, arterial blood pressures, and arterial blood gases) were recorded throughout anaesthesia. Data were analysed with nonparametric methods. RESULTS: The anaesthetic induction (P = 0.2) and recovery (P = 0.1) quality scores (median, range) were not different amongst protocols and were 4.0, 3-5; 5.0, 4-5; 4.5, 3-5; and 4.5, 3-5; 3.5, 2-5; 4.0, 2-5 for alfaxalone, ketamine and thiopental, respectively. Induction time for ketamine (67, 53-89 s) was significantly longer than that for alfaxalone (49, 40-51 s, P = 0.01) and thiopental (48, 43-50 s, P = 0.01). Time to standing for alfaxalone (44, 40-63 min, P = 0.01) and thiopental (39, 30-58 min, P = 0.01) was significantly longer than that for ketamine (25, 18-26 min). Cardiovascular values were maintained within the clinically acceptable level throughout anaesthesia. Respiratory rate significantly decreased during anaesthesia for all 3 drugs; however, spontaneous breathing did not disappear, and PaCO2 values were maintained at approximately 50 mmHg. CONCLUSIONS: All 3 drugs showed similar effects in relation to anaesthetic induction and recovery qualities and cardiopulmonary responses. However, alfaxalone and thiopental prolonged recovery time compared with ketamine. PMID- 26850883 TI - Epigenetic regulation of the histone-to-protamine transition during spermiogenesis. AB - In mammals, male germ cells differentiate from haploid round spermatids to flagella-containing motile sperm in a process called spermiogenesis. This process is distinct from somatic cell differentiation in that the majority of the core histones are replaced sequentially, first by transition proteins and then by protamines, facilitating chromatin hyper-compaction. This histone-to-protamine transition process represents an excellent model for the investigation of how epigenetic regulators interact with each other to remodel chromatin architecture. Although early work in the field highlighted the critical roles of testis specific transcription factors in controlling the haploid-specific developmental program, recent studies underscore the essential functions of epigenetic players involved in the dramatic genome remodeling that takes place during wholesale histone replacement. In this review, we discuss recent advances in our understanding of how epigenetic players, such as histone variants and histone writers/readers/erasers, rewire the haploid spermatid genome to facilitate histone substitution by protamines in mammals. PMID- 26850888 TI - [Treatment effect analysis of the standard regimen and the optimized regimen for retreatment pulmonary tuberculosis complicated with diabetes]. AB - OBJECTIVE: To analyze the therapeutic effects of the standard regimen and the optimized regimen in retreatment pulmonary tuberculosis complicated with diabetes mellitus (DM). METHODS: In a multi-center cohort study, patients with smear positive retreatment pulmonary tuberculosis (TB) with DM and those without DM [excluding multi-drug resistance (MDR), extensively drug-resistant (XDR) and non tuberculosis Mycobacterium pulmonary disease(NTM)] were enrolled. There were a total of 178 cases, including 60 smear positive retreatment TB patients with DM and 118 without DM, who were randomly divided into 4 groups: Optimized group 1 [individualized treatment in 30 DM cases, 29 males, age (48 +/- 11)], retreatment group 1 [standard retreatment regimen in 30 DM cases, 28 males, age(48 +/- 10)], Optimized group 2[individual regimen in 57 non-DM cases, 37 males, age (41 +/- 14)], and retreatment group 2 [standard retreatment regimen in 61 non-DM cases, 49 males, age (43 +/- 13)]. Patients in the optimized group were treated with optimized individualized regimen based on DST result, with 3-4 sensitive drugs in the regimen, while those in the retreatment group were treated with national standard retreatment regimen. The therapeutic effect of different groups were recorded and the related factors of treatment outcome were analyzed with Chi square test and multi-factor analysis. RESULTS: The treatment success rates of the optimized group 1 and the retreatment group 1 were 83.3%(25/30) and 60.0%(18/30), respectively, and the difference was statistically significant (chi(2)=4.02, P=0.045<0.05). The treatment failure rate of the optimized group 1 (6.7%, 2/30) and the retreatment group 1(30.0%, 9/30) was statistically different (chi(2)=5.46, P=0.02<0.05). The outcome difference between the optimized group 2 and the retreatment group 2 showed no statistical significance. Multi-factor analysis showed that treatment regimen, DM, gender and drug resistance were the significant factors related with treatment outcome. The probability of treatment success using the individualized treatment regimen was 2.7 times higher than that using the standard regimen (P=0.025). The risk of treatment failure of the drug resistance cases was 2.8 times higher than that of the drug sensitive cases (P=0.038). The probability of treatment success in DM cases was 0.4 times that in non-DM cases (P<0.05). CONCLUSION: The outcome of the optimized regimen group was better than that of the standard regimen group, and retreatment TB patients complicated with DM faced a higher risk of treatment failure, which should receive more attention. PMID- 26850889 TI - [Evaluation of T-SPOT.TB assay in the diagnosis of pulmonary tuberculosis within different age groups]. AB - OBJECTIVE: To evaluate the value of T-SPOT.TB assay in the diagnosis of pulmonary tuberculosis within different age groups. METHODS: We analyzed 1 518 suspected pulmonary tuberculosis (PTB) patients who were admitted to the Beijing Chest Hospital from November 2012 to February 2014 and had valid T-SPOT.TB tests before anti-tuberculosis therapy. The 599 microbiologically and/or histopathologically confirmed PTB patients (16-89 years old, 388 males and 211 females) and 235 non TB patients (14-85 years old, 144 males and 91 females) were enrolled for the analysis of diagnostic performance of T-SPOT.TB, while patients with uncertain diagnosis or diagnosis based on clinical impression (n=684) were excluded from the analysis. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the T-SPOT.TB were analyzed according to the final diagnosis. Furthermore, the diagnostic performance of T-SPOT.TB assay in the younger patients (14-59 years old) and elderly patients (60-89 years old) were also analyzed respectively. Categorical variables were compared by Pearson's Chi-square test, while continuous variables were compared by the Mann-Whitney U-test. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the T-SPOT.TB in diagnosis of PTB were 90.1% (540/599), 65.5% (154/235), 86.9% (540/621), 72.3% (154/213), 2.61, and 0.15, respectively. The sensitivity and specificity of T SPOT.TB assay were 92.6% (375/405) and 75.6% (99/131), respectively in the younger patients, and 85.0% (165/194), 52.9% (55/104) respectively in the elderly patients. The sensitivity and specificity of T-SPOT.TB assay in the younger patients were significantly higher than those in the elderly patients (P<0.01), and the spot forming cells in the younger PTB patients were significantly higher than in the elderly PTB patients [300 (126, 666)/10(6) PBMCs vs. 258 (79, 621)/10(6) PBMCs, P=0.037]. CONCLUSION: T-SPOT.TB is a promising test in the diagnosis of younger patients (14-59 years old) with suspected PTB, but the diagnostic performance in elderly patients (60-89 years old) is relatively reduced. PMID- 26850890 TI - [Diagnostic value of computed tomography-guided percutaneous needle biopsy versus radial probe endobronchial ultrasound-guided transbronchial lung biopsy in peripheral pulmonary lesions]. AB - OBJECTIVE: To evaluate the value of computed tomography-guided percutaneous needle biopsy (CT-PNB) and radial probe endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) in the diagnosis of peripheral pulmonary lesions(PPLs). METHODS: The clinical data of 213 patients who were diagnosed as to have PPLs in the First Affiliated Hospital of Soochow University between December 1, 2012 and October 1, 2014 were studied retrospectively. The patients were divided into CT-PNB group and EBUS-TBLB group, according to biopsy methods. The diagnostic yield, complications and influencing factors of both groups were evaluated. RESULTS: The diagnostic yield (87.2%, 102/117) and complication rate (18.8%, 22/117) of the CT-PNB group were higher than those of the EBUS-TBLB group(61.5%, 59/96 and 18.8%, 22/117, respectively), the differences being statistically significant (chi(2)=18.906, P=0.000 and chi(2)=10.542, P=0.001, respectively). Analysis of the influencing factors showed that there were statistically significant correlations between pneumothorax and the lesion diameter(chi(2)=5.785, P=0.016) and location(chi(2)=7.559, P=0.006) in the CT-PNB group. The diagnostic yield was correlated with lesion diameter(chi(2)=7.995, P=0.004) and location(chi(2)=4.608, P=0.027) in the EBUS-TBLB group. There was no complicated pneumothorax if the lesions were attached to the chest wall in the CT PNB group. CONCLUSIONS: The diagnostic yield of CT-PNB in PPLs was better than that of EBUS-TBLB. Although CT-PNB had a higher complication rates, most complications were mild. PMID- 26850891 TI - [Characteristics of subgroups classified by pulmonary function test in chronic obstructive pulmonary disease patients]. AB - OBJECTIVE: To compare the clinical characteristics and the therapeutic responses in chronic obstructive pulmonary disease (COPD) subgroups, classified by diffusing capacity of the lung for carbon monoxide (D(L)CO) and inspiratary capacity (IC). METHODS: A total of 105 mild-severe patients (70 males, 35 females, 44 to 85 years of age), with stable COPD were recruited in Cangzhou Central Hospital from June 2012 to June 2014. According to baseline D(L)CO and IC, the patients were divided into normal D(L)CO/IC group (group A, n=10), low D(L)CO/normal IC group (group B, n=18), normal D(L)CO/low IC group (group C, n=22) and low D(L)CO/IC group (group D, n=55). We compared the clinical characteristics, induced sputum cells and the therapeutic responses to 3-month treatment of budesonide/formoterol(320 ug/9 ug, inhale, bid)among the 4 groups. RESULTS: Group D showed the highest CAT scores(27.6 +/- 6.4). Group C showed a higher prevalence of patients with wheezing(81.8)% and the highest percentage of sputum eosinophils (7.6 +/- 3.2)%. Group C showed the greatest FEV(1) increase(0.214 +/- 0.053)L. Group D showed a greater FEV(1) increase than Group B [(0.137 +/- 0.063) vs (0.092 +/- 0.048)L]. Group C showed a greater FVC[(0.342 +/ 0.073), (0.190 +/- 0.081), (0.223 +/- 0.094)L] increase and CAT[(4.4 +/- 2.0), (2.3 +/- 1.3), (3.9 +/- 1.9)] decrease than Group B and Group D(P<0.05). CONCLUSION: These findings suggest that COPD subgroups classified by D(L)CO and IC show several clinical characteristics and may be helpful to predict responses to treatment. PMID- 26850892 TI - [Nose-only cigarette smoke exposure plus airway lipopolysaccharide inhalation induced chronic obstructive pulmonary disease and associated pulmonary hypertension in mice]. AB - OBJECTIVE: To establish a mouse model of chronic obstructive pulmonary disease (COPD) and associated pulmonary hypertension (COPD-PH) induced by nose-only cigarette smoking exposure plus airway lipopolysaccharide (LPS) inhalation. METHODS: There were 24 male C57B6 mice divided into a control group and a model group at random. The model group was given LPS by intranasal inhalation on day 1 and day 14 and exposed to the cigarette smoke in a nose-only exposure system, while the control group was given physiological saline and exposed to normal air. The model establishment was evaluated according the following parameters: the lung function and the right heart pressure, the total and differential cell numbers in bronchial alveolar lavage fluid (BALF), and the pathological changes of lung tissues. RESULTS: The functional residual capacity data of the model group and the control group were (0.402 +/- 0.057) and (0.243 +/- 0.064) ml respectively (P<0.05). The inspiratory resistance data of the model group and the control group were (1.056 +/- 0.121) and (0.789 +/- 0.063) cmH(2)O . ml(-1) . s( 1) (1 cmH(2)O=0.098 kPa) respectively (P<0.05). The static lung compliance data of the model group and the control group were (0.084 +/- 0 .007) and (0.056 +/- 0.004) cmH(2)O/ml respectively (P<0.05). The right ventricular mean pressure of the model group and the control group were (11.3 +/- 1.3) and (7.9 +/- 1.1) mmHg (1 mmHg=0.133 kPa) respectively (P<0.05), while the right ventricular hypertrophy index of the model group and the control group were (0.267 +/- 0.019) and (0.195 +/- 0.023) respectively (P<0.05). Moreover, the histological staining showed that goblet cell hyperplasia, lung inflammation and thickening of smooth muscle layers of bronchial and pulmonary small vessels occurred in the model group, which indicated ongoing airway and blood vessel remodeling. CONCLUSIONS: A COPD-PH mouse model was established by nose-only cigarette smoking exposure plus airway LPS inhalation in a short period of time, and this method was more similar to the smoking behavior of human. PMID- 26850893 TI - [Hypereosinophilic syndrome with first presentation of pulmonary embolism and extensive venous thrombosis: a case report and literature review]. AB - OBJECTIVE: To study the diagnosis and treatment of hypereosinophilic syndrome complicated with thromboembolism. METHODS: A retrospective analysis of a patient with hypereosinophilic syndrome diagnosed and treated in the Department of Cardiology, PLA General Hospital was performed. A literature research was performed with "hypereosinophilic syndrome" as the Chinese key word in Wanfang database and China national knowledge internet and "hypereosinophilic syndrome, hypereosinophilia, eosinophilia" as the English key words in PubMed and Embase database. The time interval was from January 1975 to December 2013. RESULTS: The patient was a 31 year old male with a history of bilateral lower limb swelling and a history of chest pain accompanied with blood-stained sputum. Computed tomography pulmonary arteriography (CTPA) on admission showed multiple filling defects at lobular and segmental arteries. CT venography (CTV) and ultrasound examination of the legs demonstrated multiple venous thrombosis. Literature review found 41 articles, including 8 reviews, 29 case reports and 4 other type articles. CONCLUSIONS: The clinical manifestations of hypereosinophilic syndrome were varied, and therefore the disease should be managed differently according to different subtypes with glucocorticoids as the main therapy. Effectively reducing the eosinophil count could decrease the incidence of thrombotic complications. Anticoagulant therapy should be used in patients with thrombotic complications. The effectiveness of preventative anticoagulation and duration of anticoagulation are less clear and require further clinical study. PMID- 26850894 TI - [Advance of microRNA in antituberculosis immunity and diagnosis of tuberculosis]. PMID- 26850895 TI - [Recent progress of antituberculosis therapy-associated acute liver failure]. PMID- 26850896 TI - [Aerosol therapy of patients receiving noninvasive positive pressure ventilation]. PMID- 26850897 TI - [Idiopathic pulmonary fibrosis: cough and its treatment]. PMID- 26850898 TI - [The research progresses of oxidative stress biomarkers in COPD]. PMID- 26850899 TI - Antiviral therapy of primary cytomegalovirus infection with vascular thrombosis in immunocompetent adults. AB - BACKGROUND: Vascular thromboembolism (VTE) complicating cytomegalovirus (CMV) primary infection is increasingly reported in immunocompetent adults. No guideline is, however, currently available for the management of these infections and particularly for the antiviral therapy indication. METHODS: We performed a literature review of VTE complicating CMV primary infection in immunocompetent adults using PubMed. RESULTS: Sixty-nine case patients of VTE complicating CMV primary infection were reported. The main sites of venous thrombosis were the splanchnic veins (30 patients) or those of the lower limbs (18 patients). One third of patients presented with pulmonary embolism (25 patients). Forty-nine patients (76%) had at least one VTE risk factor, inherited or acquired thrombophilia for 37 patients (58%), and another risk factor for 27 patients (42%). Only 11 patients received an antiviral therapy. A positive outcome was observed in all patients. CONCLUSION: We suggest that antiviral therapy should be considered for patients presenting with severe VTE, VTE with a negative outcome despite anticoagulation, severe organ involvement, or for patients managed in the intensive care unit. PMID- 26850900 TI - Possible effects of Phillyrea latifolia on weight loss in rats fed a high-energy diet. AB - Context Phillyrea latifolia L. (Oleaceae), commonly found in the Mediterranean region in Turkey, is used as medicinal teas for weight loss and hyperglycaemia in folk medicine. Objective The study investigated the possible effects of P. latifolia leaves aqueous extract's on weight loss and biochemical-histological changes in the rats fed a high-energy diet (HED), also isolated and determined the main phenolic compounds. Materials and methods Twenty-four male Wistar albino rats were divided into four equal groups such as the HED group fed a HED, the PLE group given only the extract of P. latifolia leaves (220 mg/kg), the HED + PLE group administrated with the extract of leaves (220 mg/kg) after being fed with HED and a control group fed with standard pellet diet. Results PLE administration caused a remarkable decrement of body weight in the HED + PLE group (p < 0.05). PLE showed an improved effect on structural integrity and decreased leukocyte infiltration in liver and small intestinal tissues. The blood glucose (117.3 mmol/L), leptin (5.6 ng/mL), total cholesterol (61.8 mg/dL) and LDL (9.3 mmol/L) levels were significantly increased in the HED group. PLE administration in the HED group decreased these levels. The levels of HDL (26.8 mmol/L) in the HED + PLE group were higher than both control and HED groups. Chemical composition was investigated and luteolin 7-O-glucoside and chlorogenic acid were determined for the first time in Turkish sample from the EtOAc extract of leaves. Discussion and conclusion Phillyrea latifolia leaves may have beneficial effects on obesity related cellular problems and may become a good source of antidiabetic medication. PMID- 26850901 TI - Familias Unidas for high risk adolescents: Study design of a cultural adaptation and randomized controlled trial of a U.S. drug and sexual risk behavior intervention in Ecuador. AB - BACKGROUND: Developing, testing and implementing evidence-based prevention interventions are important in decreasing substance use and sexual risk behavior among adolescents. This process requires research expertise, infrastructure, resources and decades of research testing, which might not always be feasible for low resource countries. Adapting and testing interventions proven to be efficacious in similar cultures might circumvent the time and costs of implementing evidence-based interventions in new settings. This paper describes the two-phase study, including training and development of the research infrastructure in the Ecuadorian university necessary to implement a randomized controlled trial. METHODS/DESIGN: Familias Unidas is a multilevel parent-centered intervention designed in the U.S. to prevent drug use and sexual risk behaviors in Hispanic adolescents. The current study consisted of Phase 1 feasibility study (n=38) which adapted the intervention and study procedures within a single-site school setting in an area with a high prevalence of drug use and unprotected sexual behavior among adolescents in Ecuador, and Phase 2 randomized controlled trial of the adapted intervention in two public high schools with a target population of families with adolescents from 12 to 14 years old. DISCUSSION: The trial is currently in Phase 2. Study recruitment was completed with 239 parent youth dyads enrolling. The intervention phase and the first follow-up assessment have been completed. The second and third follow-up assessments will be completed in 2016. This project has the potential of benefitting a large population of families in areas of Ecuador that are disproportionally affected by drug trafficking and its consequences. TRIAL REGISTRATION: MSP-DIS-2015-0055-0, Ministry of Public Health (MSP), Quito, Ecuador. PMID- 26850903 TI - Mast cell activation disease and the modern epidemic of chronic inflammatory disease. AB - A large and growing portion of the human population, especially in developed countries, suffers 1 or more chronic, often quite burdensome ailments which either are overtly inflammatory in nature or are suspected to be of inflammatory origin, but for which investigations to date have failed to identify specific causes, let alone unifying mechanisms underlying the multiple such ailments that often afflict such patients. Relatively recently described as a non-neoplastic cousin of the rare hematologic disease mastocytosis, mast cell (MC) activation syndrome-suspected to be of greatly heterogeneous, complex acquired clonality in many cases-is a potential underlying/unifying explanation for a diverse assortment of inflammatory ailments. A brief review of MC biology and how aberrant primary MC activation might lead to such a vast range of illness is presented. PMID- 26850902 TI - High-density lipoprotein and inflammation in cardiovascular disease. AB - Great advances are being made at the mechanistic level in the understanding of the structural and functional diversity of high-density lipoprotein (HDL). HDL particle subspecies of different sizes are now known to differ in the protein and lipid cargo they transport, conferring on them the ability to perform different functions that in aggregate would be expected to provide protection against the development of atherosclerosis and its downstream clinical consequences. Exacerbating what is already a very complex system is the finding that inflammation, via alteration of the proteomic and lipidomic composition of HDL subspecies, can modulate at least some of their functional activities. In contrast to the progress being made at the mechanistic level, HDL epidemiologic research has lagged behind, largely because the simple HDL biomarkers used (mainly just HDL cholesterol) lack the needed complexity. To address this deficiency, analyses will need to use multiple HDL subspecies and be conducted in such a way as to eliminate potential sources of confounding. To help account for the modulating influence of inflammation, effective use must also be made of inflammatory biomarkers including searching systematically for HDL-inflammation interactions. Using nuclear magnetic resonance (NMR)-measured HDL subclass data and a novel NMR-derived inflammatory biomarker, GlycA, we offer a case study example of the type of analytic approach considered necessary to advance HDL epidemiologic understanding. PMID- 26850904 TI - Analysing predictors for future high-cost patients using German SHI data to identify starting points for prevention. AB - BACKGROUND: Demographic change influences not only the terms of health care, but also its financing. Hence, prevention is becoming a more important key to facing upcoming challenges. Aim of this study was to identify predictors for future high cost patients and derive implications for potential starting points for prevention. METHODS: Claims data from a German statutory health insurance agency were used. High-cost patients were defined as the 10% most expensive persons to insure in 2011. The predictors stemmed from the previous year. Logistic regression with stepwise forward selection for 10 sex- and age-specific subgroups was performed. Model fit was assessed by Nagelkerke's R-squared value. RESULTS: Model fit values indicated well-suited models that yielded better results among younger age-groups. Identified predictors can be summarized as different sets of variables that mostly pertain to diseases. Some are rather broad and include different disorders, like the set of mental/behavioural disorders including depression and schizophrenia; other sets of variables are more homogenous, such as metabolic diseases, with diabetes mellitus (DM) being the dominant member of every subgroup. CONCLUSION: Because diabetes was a significant predictor for future high-cost patients in all analysed subgroups, it should be considered as a potential starting point for prevention. The disease is specific enough to allow for the implementation of effective prevention strategies, and it is possible to intervene, even in patients already affected by DM. Furthermore, the monetary savings potential is probably high because the long-term complications of DM are expensive to treat and affect a large part of the population. PMID- 26850905 TI - Economic Evaluations of Public Health Surveillance Systems: a Systematic Review. PMID- 26850906 TI - 'Pre-prosthetic use of poly(lactic-co-glycolic acid) membranes treated with oxygen plasma and TiO2 nanocomposite particles for guided bone regeneration processes'. AB - OBJECTIVES: Guided bone regeneration (GBR) processes are frequently necessary to achieve appropriate substrates before the restoration of edentulous areas. This study aimed to evaluate the bone regeneration reliability of a new poly-lactic-co glycolic acid (PLGA) membrane after treatment with oxygen plasma (PO2) and titanium dioxide (TiO2) composite nanoparticles. METHODS: Circumferential bone defects (diameter: 10mm; depth: 3mm) were created on the parietal bones of eight experimentation rabbits and were randomly covered with control membranes (Group 1: PLGA) or experimental membranes (Group 2: PLGA/PO2/TiO2). The animals were euthanized two months afterwards, and a morphologic study was then performed under microscope using ROI (region of interest) colour analysis. Percentage of new bone formation, length of mineralised bone formed in the grown defects, concentration of osteoclasts, and intensity of osteosynthetic activity were assessed. Comparisons among the groups and with the original bone tissue were made using the Kruskal-Wallis test. The level of significance was set in advance at a=0.05. RESULTS: The experimental group recorded higher values for new bone formation, mineralised bone length, and osteoclast concentration; this group also registered the highest osteosynthetic activity. Bone layers in advanced formation stages and low proportions of immature tissue were observed in the study group. CONCLUSIONS: The functionalised membranes showed the best efficacy for bone regeneration. CLINICAL SIGNIFICANCE: The addition of TiO2 nanoparticles onto PLGA/PO2 membranes for GBR processes may be a promising technique to restore bone dimensions and anatomic contours as a prerequisite to well-supported and natural appearing prosthetic rehabilitations. PMID- 26850907 TI - Pediatric abdominal injury patterns caused by "falls": A comparison between nonaccidental and accidental trauma. AB - BACKGROUND/PURPOSE: Falling from a low height is the most common history given by caregivers of pediatric nonaccidental trauma (NAT) victims evaluated for blunt abdominal trauma (BAT). The purpose of this study is to compare the patterns of injuries seen in children with BAT who are victims of NAT with those seen after a fall-related incident. METHODS: Trauma database query from regional pediatric trauma centers identified patients were who were evaluated for BAT resulting from either NAT or a fall. Study groups included patients younger than five years who were (1) victims or NAT, or (2) fall casualties. RESULTS: Sixty-five NATs and 115 fall casualties were identified. NAT victims had higher ISS, had more severe head injuries according to AIS scores, had more hollow viscus injuries, and had more pancreatic injuries. Fall casualties were more likely to have solid organ injuries. CONCLUSIONS: When evaluating children with a history of blunt abdominal trauma caused by a fall, suspicion for NAT is warranted if the child is younger than five years, has a hollow viscus, pancreatic, and/or severe head injury and has a high ISS. Likewise, isolated splenic or renal injury allays suspicion for NAT. PMID- 26850908 TI - The role of ischemia in necrotizing enterocolitis. AB - AIM: The role of ischemia in the pathogenesis of necrotizing enterocolitis (NEC) remains unclear. We used immunohistochemical markers of hypoxia to identify presence/absence of ischemia in NEC and spontaneous intestinal perforation (SIP) with clinical correlation. METHODS: Immunohistochemical staining was performed on 24 NEC and 13 SIP intestinal resection specimens using 2 hypoxia markers, hypoxia inducible factor 1alpha (HIF-1alpha) and glucose transporter 1 (GLUT1) and inflammatory markers, leukocyte common antigen (LCA) and myeloperoxidase. Ischemic score (0-6) from the sum of the HIF-1alpha and GLUT1 staining intensity grades was devised (positive >=3). Inflammation was graded from the sum of LCA and myeloperoxidase grading. Relevant clinical information was obtained from hospital case records. RESULTS: Fourteen NEC specimens had positive ischemic score (4.6+/-1.2). The remaining 10 NEC (ischemic score 0.7+/-0.8) and all 13 SIP samples (ischemic score 0.5+/-0.5) were ischemic-negative. The ischemic-positive cases had classic NEC with multiple areas of bowel necrosis; were associated with later onset, enteral feeding and pneumatosis. In contrast, all ischemic-negative NEC were short-segment NEC with perforation. Their clinical profile was similar to the SIP cases with younger gestational age at birth, early onset, association with ibuprofen/indomethacin usage but not with feeding and pneumatosis. Ischemic scores are correlated with inflammation scores in mucosa but not submucosa. CONCLUSIONS: Ischemia as assessed with immunohistochemical markers HIF-1alpha and GLUT1, has a primary role in pathogenesis of classic NEC only, not in SIP or short-segment NEC with perforation. Better categorization of the different types of NEC can direct appropriate prevention and treatment strategies. PMID- 26850909 TI - Gastric teratoma: A series of 7 cases. AB - BACKGROUND: Gastric teratoma is a rare entity comprising less than 1% of germ cell tumors of childhood. We present a series of seven gastric teratomas with a review of literature. OBJECTIVE: To study the demographic profile, clinicopathological features and follow-up data of gastric teratomas. METHODS: We did a retrospective analysis of 7 cases of gastric teratomas more than 15years and studied their demographic profiles, clinicopathological features and follow up data. RESULTS: We came across 7 cases of gastric teratomas out of which 5 were mature and 2 were immature. One case of immature teratoma came back with recurrence and another one had an unusual finding of presence of renal and pulmonary tissues, which has not been reported earlier. CONCLUSION: Ours is the second largest case series of gastric teratomas in the pediatric age group and 2 out of 7 of our cases had immature elements. We also take this opportunity to report a case of gastric teratoma with the unusual histological finding of immature renal and pulmonary tissues, which has not been described previously. PMID- 26850911 TI - Possible efficacy of recombinant human soluble thrombomodulin for the treatment of thrombotic microangiopathy after liver transplantation. PMID- 26850910 TI - Comparison of transumbilical laparoscopic-assisted appendectomy versus single incision laparoscopic appendectomy in children: which is the better surgical option? AB - BACKGROUND: Transumbilical laparoscopic-assisted appendectomy (TULA) is a single incision technique that exteriorizes the appendix through the umbilicus. The aim of this study was to compare the surgical outcomes of TULA with SILA in pediatric appendicitis. METHODS: A retrospective review of medical records between April 2011 and April 2015 identified 250 pediatric patients who underwent single incision laparoscopic appendectomy. Of these, 137 patients underwent TULA and 113 patients underwent SILA. Measured outcomes included patients' demographics, clinical characteristics, operative time, length of stay, pain, and postoperative complications. RESULTS: TULA group had a shorter operative time than SILA group (28.93 vs. 49.19min, p<0.001). The use of rescue analgesics was more frequent in the SILA group (six cases (6.5%) vs. 19 cases (23.4%), p<0.001). There was no significant difference in cosmetic outcome between the two groups. However, TULA was associated with a lower complication rate (2/137, 1.5%) than SILA (11/113, 9.8%) (p=0.0035). In multiple logistic regression analysis, TULA was significantly associated with a lower complication rate (p=0.049). CONCLUSIONS: TULA is preferable to SILA for treating pediatric acute appendicitis because it is technically easier, results in better surgical outcomes, and provides the same excellent cosmetic results. PMID- 26850912 TI - Cellular Ontogeny and Hierarchy Influence the Reprogramming Efficiency of Human B Cells into Induced Pluripotent Stem Cells. AB - Although B cells have been shown to be refractory to reprogramming into pluripotency, induced pluripotent stem cells (iPSCs) have been very recently generated, at very low efficiency, from human cord blood (CB)- and peripheral blood (PB)-derived CD19+CD20 + B cells using nonintegrative tetracistronic OSKM expressing Sendai Virus (SeV). Here, we addressed whether cell ontogeny and hierarchy influence the reprogramming efficiency of the B-cell compartment. We demonstrate that human fetal liver (FL)-derived CD19 + B cells are 110-fold easier to reprogram into iPSCs than those from CB/PB. Similarly, FL-derived CD34+CD19 + B progenitors are reprogrammed much easier than mature B cells (0.46% vs. 0.11%). All FL B-cell iPSCs carry complete VDJH rearrangements while 55% and 45% of the FL B-progenitor iPSCs carry incomplete and complete VDJH rearrangements, respectively, reflecting the reprogramming of developmentally different B progenitors (pro-B vs. pre-B) within a continuous differentiation process. Finally, our data suggest that successful B-cell reprogramming relies on active cell proliferation, and it is MYC-dependent as identical nonintegrative polycistronic SeV lacking MYC (OSKL or OSKLN) fail to reprogram B cells. The ability to efficiently reprogram human fetal primary B cells and B precursors offers an unprecedented opportunity for studying developmental B-lymphopoiesis and modeling B-cell malignances. PMID- 26850914 TI - Nodular gill disease in farmed rainbow trout (Oncorhynchus mykiss) in Italy. PMID- 26850913 TI - Rising Energetic Cost of Walking Predicts Gait Speed Decline With Aging. AB - BACKGROUND: Slow gait is a robust biomarker of health and a predictor of functional decline and death in older adults, yet factors contributing to the decline in gait speed with aging are not well understood. Previous research suggests that the energetic cost of walking at preferred speed is inversely associated with gait speed, but whether individuals with a rising energetic cost of walking experience a steeper rate of gait speed decline has not been investigated. METHODS: In participants of the Baltimore Longitudinal Study of Aging, the energetic cost of overground walking at preferred speed (mL/kg/m) was assessed between 2007 and 2014 using a portable indirect calorimeter. The longitudinal association between the energetic cost of walking and usual gait speed over 6 meters (m/s) was assessed with multivariate linear regression models, and the risk of slow gait (<1.0 m/s) was analyzed using Cox proportional hazards models. RESULTS: The study population consisted of 457 participants aged 40 and older who contributed 1,121 person-visits to the analysis. In fully adjusted models, increases in the energetic cost of walking predicted the rate of gait speed decline in those older than 65 years (beta = -0.008 m/s, p < .001). Moreover, those with a higher energetic cost of walking (>0.17mL/kg/m) had a 57% greater risk of developing slow gait compared with a normal energetic cost of walking (<=0.17mL/kg/m; adjusted hazard ratio = 1.57, 95% confidence interval: 1.01-2.46). CONCLUSIONS: These findings suggest that strategies to maintain walking efficiency hold significant implications for maintaining mobility in late life. Efforts to curb threats to walking efficiency should focus on therapies to treat gait and balance impairments, and reduce clinical disease burden. PMID- 26850915 TI - Influence of the configurational pattern of sp(2)-iminosugar pseudo N-, S-, O- and C-glycosides on their glycoside inhibitory and antitumor properties. AB - The synthesis of a complete series of cyclic carbamate-type sp(2)-iminosugar N-, S-, O- and C-octyl pseudoglycosides related to nojirimycin, mannojirimycin and galactonojirimycin, all having the alpha-pseudoanomeric configuration, is reported. The gem-diamine-type N-pseudoglycosides can be accessed directly from the corresponding reducing sp(2)-imisosugar precursors by reaction with octylamine in methanol, whereas per-O-acetyl or 1-fluoro derivatives were used as pseudoglycosyl donors for the preparation of S-pseudoglycosides or O- and C pseudoglycosides, respectively. Evaluation of their inhibitory properties against a panel of glycosidases evidenced selectivity profiles that strongly depend on the configurational pattern and the nature of the glycosidic linkage. On the contrary, the antiproliferative activity determined against a panel of tumor cell lines was largely independent of the relative orientation of the hydroxyl groups in the sp(2)-iminosugar moiety. Indeed, sp(2)-iminosugar representatives exhibiting significant growth inhibition potencies were identified in all three configurationally different types of compounds studied, namely alpha-d-gluco, alpha-d-manno and alpha-d-galacto glycoside analogs. Interestingly, none of the compounds affected viability and mortality of normal cells at the used concentrations. Altogether, the results strongly suggest that the anticancer activity of amphiphilic sp(2)-iminosugar glycosides might be unrelated, or not solely related, to their glycosidase inhibitory activity. PMID- 26850916 TI - Targeted and exome sequencing identified somatic mutations in hepatocellular carcinoma. AB - AIM: Genetic analysis has revealed a subset of recurrently mutated genes and aberrant cellular signaling pathways in hepatocellular carcinoma. To investigate genetic alterations and dysregulated pathways in hepatocellular carcinoma, we performed targeted sequencing and exome analysis using next-generation sequencer. METHODS: We analyzed the somatic mutational profiles of 16 genes in primary hepatocellular carcinoma by targeted ultra-deep sequencing using nine pairs of specimens (tumor and peripheral blood) and whole-exome sequencing using one pair of samples. RESULTS: Overall, somatic mutations with high allele fraction were identified in tumor tissues by targeted deep sequencing. Somatic mutations with high allele fraction were observed in TP53 (3/9; 33%) and CTNNB1 (2/9; 22%) genes in five out of nine (55%) specimens. In vitro analysis showed that CTNNB1 H36P mutant protein identified in tumor samples was resistant to protein degradation and promoted cell proliferation. Exome sequencing identified SLIT3 mutation, implying that dysregulation of axon guidance genes is involved in the development of hepatocellular carcinoma. These results showed that TP53 and WNT/beta-catenin signaling pathways were commonly mutated in hepatocellular carcinoma. CONCLUSION: These results suggest that targeted sequencing and exome sequencing enable the identification of putative oncogenic driver mutations during the development of hepatocarcinoma. PMID- 26850917 TI - Nrf2 activator ameliorates hemorrhagic transformation in focal cerebral ischemia under warfarin anticoagulation. AB - BACKGROUND AND PURPOSE: Oxidative stress has been reported to be a main cause of neuronal cell death in ischemia reperfusion injury (IRI). Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important factor involved in anti oxidative responses. We previously reported that bardoxolone methyl (BARD), an Nrf2 activator, prevented damage induced by IRI. In this study, we investigated the effect of BARD on hemorrhagic transformation in the context of blood brain barrier (BBB) protection. METHODS: Mice received pre-treatment with warfarin (4.0 mg/kg, p.o.). IRI was subsequently induced 18 h after the warfarin administration by transient middle cerebral artery occlusion (MCAO) for 6 h. BARD (0.06, 0.2, 0.6 or 2.0 mg/kg) or saline was injected intravenously immediately after reperfusion. The infarct volume, neurological score, intracranial hemorrhage volume, and BBB permeability were evaluated 24 h after MCAO. The survival rate and behavioral functional recovery were evaluated for 7 days following IRI. Furthermore, the effects of BARD on BBB components were investigated by western blotting and immunostaining analysis. RESULTS: BARD suppressed warfarin-mediated increases in the intracranial hemorrhage volume without affecting the infarct volume. BBB permeability was also suppressed by administration of BARD. Western blotting showed that BARD increased expression of BBB components such as endothelial cells, pericytes, and tight junction proteins. Furthermore, immunostaining showed that BARD induced localization of Nrf2 to endothelial cells and pericytes. CONCLUSIONS: BARD suppressed the exacerbation hemorrhage caused by warfarin pretreatment and ameliorated BBB disruption by protecting endothelial cells, pericytes, and tight junction protein expressions. These results indicate that Nrf2 activators may be an effective therapy against hemorrhagic transformation caused by anticoagulant drugs. PMID- 26850919 TI - Irish coffee: Effects of alcohol and caffeine on object discrimination in zebrafish. AB - Many studies regarding the effects of drugs investigate the acute and chronic use of alcohol, but only a few address the effects of caffeine and alcohol combined to the performance of the zebrafish in cognitive tasks. The zebrafish is an important model for studying the effects of drugs on learning, because it has large genetic similarities to humans and the non-invasive administration of the substances favors translational bias of research. In this study, we observed the effects of alcohol and caffeine on zebrafish cognition through an object discrimination test. We noticed that animals subjected to acute alcohol dose and those under alcohol or caffeine withdrawal did not show discrimination. When fish were treated with associated alcohol and caffeine, those chronically treated with alcohol and subjected to moderate acute dose of caffeine showed learning of the task. Our results reinforce the harmful effects of the alcohol use on cognitive tasks, and suggest that continued use of high doses of caffeine cause cognitive impairment during withdrawal of the substance. However, the acute use of caffeine appears to reverse the harmful effects of alcohol withdrawal, allowing discriminative performance equivalent to control fish. Finally, we reiterate the use of zebrafish as a model for drug effects screening and search for active compounds that modulate the alcohol and caffeine effects. PMID- 26850918 TI - Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome. AB - Sensory processing deficits are common in autism spectrum disorders, but the underlying mechanisms are unclear. Fragile X Syndrome (FXS) is a leading genetic cause of intellectual disability and autism. Electrophysiological responses in humans with FXS show reduced habituation with sound repetition and this deficit may underlie auditory hypersensitivity in FXS. Our previous study in Fmr1 knockout (KO) mice revealed an unusually long state of increased sound-driven excitability in auditory cortical neurons suggesting that cortical responses to repeated sounds may exhibit abnormal habituation as in humans with FXS. Here, we tested this prediction by comparing cortical event related potentials (ERP) recorded from wildtype (WT) and Fmr1 KO mice. We report a repetition-rate dependent reduction in habituation of N1 amplitude in Fmr1 KO mice and show that matrix metalloproteinase-9 (MMP-9), one of the known FMRP targets, contributes to the reduced ERP habituation. Our studies demonstrate a significant up-regulation of MMP-9 levels in the auditory cortex of adult Fmr1 KO mice, whereas a genetic deletion of Mmp-9 reverses ERP habituation deficits in Fmr1 KO mice. Although the N1 amplitude of Mmp-9/Fmr1 DKO recordings was larger than WT and KO recordings, the habituation of ERPs in Mmp-9/Fmr1 DKO mice is similar to WT mice implicating MMP-9 as a potential target for reversing sensory processing deficits in FXS. Together these data establish ERP habituation as a translation relevant, physiological pre-clinical marker of auditory processing deficits in FXS and suggest that abnormal MMP-9 regulation is a mechanism underlying auditory hypersensitivity in FXS. SIGNIFICANCE: Fragile X Syndrome (FXS) is the leading known genetic cause of autism spectrum disorders. Individuals with FXS show symptoms of auditory hypersensitivity. These symptoms may arise due to sustained neural responses to repeated sounds, but the underlying mechanisms remain unclear. For the first time, this study shows deficits in habituation of neural responses to repeated sounds in the Fmr1 KO mice as seen in humans with FXS. We also report an abnormally high level of matrix metalloprotease-9 (MMP-9) in the auditory cortex of Fmr1 KO mice and that deletion of Mmp-9 from Fmr1 KO mice reverses habituation deficits. These data provide a translation relevant electrophysiological biomarker for sensory deficits in FXS and implicate MMP-9 as a target for drug discovery. PMID- 26850920 TI - Chronic caffeine produces sexually dimorphic effects on amphetamine-induced behavior, anxiety and depressive-like behavior in adolescent rats. AB - Caffeine consumption has been increasing rapidly in adolescents; however, most research on the behavioral effects of caffeine has been conducted in adults. Two experiments were conducted in which adolescent male and female rats were treated with a moderate dose of caffeine (0.25 g/l) in their drinking water beginning on P26-28. In the first experiment, animals were maintained on caffeinated drinking water or normal tap water for 14 days and were then tested for behavioral and striatal c-Fos response to amphetamine (1.5 mg/kg). In the second experiment, rats were maintained on caffeinated drinking water or normal tap water beginning on P28 and were tested for novel object recognition, anxiety in the light/dark test (L/D) and elevated plus maze (EPM), and depressive like behavior in the forced swim test (FST) beginning on the 14th day of caffeine exposure. Caffeine decreased amphetamine-induced rearing in males, but had no effect in females; however, this behavioral effect was not accompanied by changes in striatal c-Fos, which was increased by amphetamine but not altered by caffeine. No effects of caffeine were observed on novel object recognition or elevated plus maze behavior. However, in the L/D test, there was a sex by caffeine interaction on time spent in the light driven by a caffeine-induced increase in light time in the males but not the females. On the pretest day of the FST, sex by caffeine interactions were observed for swimming and struggling; caffeine decreased struggling behavior and increased swimming behavior in males and caffeine-treated females demonstrated significantly more struggling and significantly less swimming than caffeine-treated males. A similar pattern was observed on the test day in which caffeine decreased immobility overall and increased swimming. These data reveal sex dependent effects of caffeine on behavior in adolescent rats. PMID- 26850921 TI - The current status and future prospects of computer-assisted hip surgery. AB - The advances in computer assistance technology have allowed detailed three dimensional preoperative planning and simulation of preoperative plans. The use of a navigation system as an intraoperative assistance tool allows more accurate execution of the preoperative plan, compared to manual operation without assistance of the navigation system. In total hip arthroplasty using CT-based navigation, three-dimensional preoperative planning with computer software allows the surgeon to determine the optimal angle of implant placement at which implant impingement is unlikely to occur in the range of hip joint motion necessary for daily activities of living, and to determine the amount of three-dimensional correction for leg length and offset. With the use of computer navigation for intraoperative assistance, the preoperative plan can be precisely executed. In hip osteotomy using CT-based navigation, the navigation allows three-dimensional preoperative planning, intraoperative confirmation of osteotomy sites, safe performance of osteotomy even under poor visual conditions, and a reduction in exposure doses from intraoperative fluoroscopy. Positions of the tips of chisels can be displayed on the computer monitor during surgery in real time, and staff other than the operator can also be aware of the progress of surgery. Thus, computer navigation also has an educational value. On the other hand, its limitations include the need for placement of trackers, increased radiation exposure from preoperative CT scans, and prolonged operative time. Moreover, because the position of a bone fragment cannot be traced after osteotomy, methods to find its precise position after its movement need to be developed. Despite the need to develop methods for the postoperative evaluation of accuracy for osteotomy, further application and development of these systems are expected in the future. PMID- 26850922 TI - Osteochondral transplantation with a dynamic external fixator is useful treatment for traumatic osteochondral defect of the finger. A case report. PMID- 26850923 TI - Comparative analysis of dual-phase 18F-fluoride PET/CT and three phase bone scintigraphy in the evaluation of septic (or painful) hip prostheses: A prospective study. AB - BACKGROUND: The preoperative differentiation of aseptic and septic loosening of hip prostheses remains a diagnostic challenge for clinicians and many molecular imaging techniques have been evaluated. The objective of current study was to establish the clinical utility of dual phase 18F-fluoride PET/CT (DPFP) in diagnosing implant loosening, differentiation between septic and aseptic loosening and to compare the diagnostic accuracy of DPFP and three-phase bone scan (TPBS). METHODS: In this prospective study, we evaluated 57 hip components in 45 patients (bilateral prostheses in 12 patients, 45 painful and 12 asymptomatic contralateral hip components) with dual phase fluoride PET/CT and TPBS. Findings of skeletal scintigraphy and PET/CT were evaluated by two expert nuclear medicine physicians, blinded with clinical findings and final diagnosis. The patterns of tracer uptake and maximum standardized uptake value (SUVmax) were noted for each joint. The final diagnosis was based on intraoperative findings, histopathological or microbiological examinations. RESULTS: Out of twelve non painful hips, DPFP correctly identified no loosening in 11 hips while TPBS detected in 10 hips. In the remaining 45 hips with radiological proven loosening to rule out sepsis, DPFP had a sensitivity, specificity, PPV, NPV and accuracy of 75%, 97%, 92%, 88% and 88% respectively while TPBS revealed 81%, 86%, 76%, 89% and 82% respectively. DPFP had shown a higher specificity and PPV as compared to the TPBS in the evaluation of painful hip prostheses. The pattern of tracer uptake may help in the differentiation between the two entities. We also noted a significant difference between SUVmax values of septic and aseptic loosening. CONCLUSIONS: The results suggested that DPFP has considerable potential in differentiating septic from aseptic loosening of hip prostheses and more specific to rule out sepsis than TPBS. It may be employed before revision arthroplasty to evaluate implant for loosening and sepsis in loosened implant. PMID- 26850924 TI - State-of-the-art management of low back pain in athletes: Instructional lecture. AB - In this paper, we describe "state of the art" on the diagnosis and treatment for low back pain in athletes. Lumbar motion that induces specific pain would be a clue to the exact diagnosis. In the flexion pain group, lumbar herniated nucleus pulposus is the most common disorder. Discogenic pain and type 1 Modic endplate inflammation may also cause flexion pain; however, the diagnosis is sometimes difficult. In children and adolescents, apophyseal ring fracture is prevalent. In the extension pain group, lumbar spondylolysis is very common, especially in pediatric athletes. In adults, facet pain due to overloading would be the pathology, while low back pain with trunk rotation is not common. However, throwing athletes, such as pitchers and hammer throwers, may experience this kind of pain; facet arthritis contralateral to the throwing arm would be the origin of the pain. Low back pain on lumbar lateral bending is rare, but we experienced some cases in golfers in whom type 1 Modic change at the lateral corner was the source of pain. In this article, we explained strategies for state-of-the-art diagnosis and minimally invasive treatment. PMID- 26850925 TI - In situ monitoring of Shewanella oneidensis MR-1 biofilm growth on gold electrodes by using a Pt microelectrode. AB - Much attention has been focused on electrochemically active bacteria (EAB) in the application of bioelectrochemical systems (BESs). Studying the EAB biofilm growth mechanism as well as electron transfer mechanism provides a route to upgrade BES performance. But an effective bacterial growth monitoring method on the biofilm scale is still absent in this field. In this work, electrode-attached bacterial biofilms formed by Shewanella oneidensis MR-1 were dynamically monitored through a microelectrode method. For S. oneidensis MR-1, a respiratory electron transport chain is associated with the secretion of riboflavin, severing as the cofactor to the outer membrane c-type cytochromes. The biofilm growth was monitored through adopting riboflavin as an electrochemical probe during the approach of the microelectrode to the biofilm external surface. This method allows in vivo and in situ biofilm monitoring at different growth stages without destructive manipulation. Furthermore, the biofilm growth monitoring results have been proved to be relatively accurate through observation under confocal laser scanning microscopy. We further applied this method to investigate the effects of four environmental factors (the concentrations of dissolved oxygen, sodium lactate, riboflavin as well as the electrode potential) on S. oneidensis MR-1 biofilm development. PMID- 26850926 TI - A prospective picture collection study for a grading atlas of radiation dermatitis for clinical trials in head-and-neck cancer patients. AB - Radiation dermatitis is one of the most common acute toxicities of both radiotherapy and chemoradiotherapy. Many clinical trials have evaluated the level of toxicity using the Common Terminology Criteria for Adverse Events ver. 4.03. This criterion accounts for severity in a single sentence only, and no visual classification guide has been available. Thus, there is a risk of subjective interpretation by the individual investigator. This contrasts with the situation with hematologic toxicities, which can be interpreted objectively. The aim of this prospective picture collection study was to develop a grading tool for use in establishing the severity of radiation dermatitis in clinical trials. A total of 118 patients who were scheduled to receive definitive or postoperative radiotherapy or chemoradiotherapy were enrolled from the four participating cancer centers. All researchers in our group used the same model of camera under the same shooting conditions to maintain consistent photographic quality. In all, 1600 photographs were collected. Of these, 100 photographs qualified for the first round of selection and were then graded by six experts, basically in accordance with the CTCAE ver. 4.03 (JCOG ver. in Japanese). After further study, 38 photographs were selected as representing typical models for Grade 1-4 radiation dermatitis; the radiation dermatitis grading atlas was produced from these photographs. The atlas will play a major role in ensuring that the dermatitis rating system is consistent between the institutions participating in trials. We hope that this will contribute to improving the quality of clinical trials, and also to improving the level of routine clinical practice. PMID- 26850927 TI - Non-induction of radioadaptive response in zebrafish embryos by neutrons. AB - In vivo neutron-induced radioadaptive response (RAR) was studied using zebrafish (Danio rerio) embryos. The Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility at the National Institute of Radiological Sciences (NIRS), Japan, was employed to provide 2-MeV neutrons. Neutron doses of 0.6, 1, 25, 50 and 100 mGy were chosen as priming doses. An X-ray dose of 2 Gy was chosen as the challenging dose. Zebrafish embryos were dechorionated at 4 h post fertilization (hpf), irradiated with a chosen neutron dose at 5 hpf and the X-ray dose at 10 hpf. The responses of embryos were assessed at 25 hpf through the number of apoptotic signals. None of the neutron doses studied could induce RAR. Non-induction of RAR in embryos having received 0.6- and 1-mGy neutron doses was attributed to neutron-induced hormesis, which maintained the number of damaged cells at below the threshold for RAR induction. On the other hand, non induction of RAR in embryos having received 25-, 50- and 100-mGy neutron doses was explained by gamma-ray hormesis, which mitigated neutron-induced damages through triggering high-fidelity DNA repair and removal of aberrant cells through apoptosis. Separate experimental results were obtained to verify that high-energy photons could disable RAR. Specifically, 5- or 10-mGy X-rays disabled the RAR induced by a priming dose of 0.88 mGy of alpha particles delivered to 5-hpf zebrafish embryos against a challenging dose of 2 Gy of X-rays delivered to the embryos at 10 hpf. PMID- 26850928 TI - Comparison of bacterial counts in expressed breast milk following standard or strict infection control regimens in neonatal intensive care units: compliance of mothers does matter. AB - Bacterial counts in 1466 expressed breast milk (EBM) samples from women following one of two infection control regimens (standard vs strict) were investigated. Overall, 12% of samples yielded Gram-negative bacteria, with no significant differences between the standard [11.9% (94/788)] and strict [12.1% (82/678)] regimens (P = 0.92). Significantly more samples were contaminated when expressed at home (standard regimen home/hospital: 17.9% vs 6.1%; strict regimen home/hospital: 19.6% vs 3.4%; P < 0.001). Bacterial contamination of EBM was not associated with the regimen, but was associated with the location of breast milk expression. Attempts to improve personal hygiene during milk collection seem to be of limited value. Good hygiene of collection and storage equipment is likely to be the most important way to ensure the microbiological quality of EBM. PMID- 26850929 TI - Structural and Functional Characterization of Hirudin P6 Derived Novel Bivalent Thrombin Inhibitors - Studying the Effect of Linker Length and Glycosylation on Their Function. AB - HirudinP6 is a glycosylated and sulfated high affinity thrombin inhibitory protein isolated from Hirudineria manillensis. In this study, designing of novel bivalent thrombin inhibitory peptides based on this hirudin isoform is described. The structural and functional impact of varying linker length and glycosylation on their inhibitory potencies and binding kinetics were assessed. The bivalent peptides were obtained by tethering an active site blocking fPRP motif with the carboxy terminal 22 residue segment of hirudin P6 (HP642-63 ) by varying number of glycine residues in the linker region. Among them, analog BiG1 -HP6 inhibited thrombin with a Ki of 5.12 nm which was comparable to that of glycosylated (disaccharide bearing) and non-sulfated full length hirudin P6 protein (Ki = 6.38 nm). Binding kinetics studies revealed increasing linker length can decrease the association rates of peptide?thrombin interactions. Similarly, glycosylation was found to negatively modulate the inhibitory potencies of these peptides by decreasing their rates of association with thrombin. Molecular docking studies revealed that increasing linker length can compromise the electrostatic interactions with the prime subsite residues of thrombin and provided structural explanation for the observed effect of linker length on association rates. These findings thus enhance our understanding of thrombin?(glyco)peptide interactions and provide key insights into the designing of efficient thrombin inhibitors and allosteric modulators of therapeutic potential. PMID- 26850930 TI - Is it possible to cure myeloma without allogeneic transplantation? AB - During the last decades, a better understanding of the biology of multiple myeloma (MM) has led to the application of novel treatment strategies for MM patients. The new anti-myeloma regimens produce higher incidence of durable and of better quality responses and they improve overall survival, challenging the dogma of incurable disease, outside the context of allogeneic transplantation. This review presents all these strategies that aim to cure MM, including continuous treatment i.e. induction, consolidation and maintenance, treatment of asymptomatic MM and monitoring minimal residual disease using modern techniques, such as multi-parameter flow cytometry, molecular assays and advanced imaging. PMID- 26850931 TI - Quality of Life After Left Ventricular Assist Device Implantation: In a World Full of Data, #Missingness. PMID- 26850932 TI - Heterologous expression of melanopsin: Present, problems and prospects. AB - Melanopsin, the photosensory pigment of specialized mammalian retinal ganglion cells, is involved in various non-image forming tasks such as pupillary light reflex, circadian entrainment and irradiance detection. Melanopsin genes have been detected in all vertebrate classes and are resolved in two lineages, Opn4m and Opn4x. In addition, two splice variants have been found in several species leading to a short (OPN4-S) and a long (OPN4-L) isoform, mainly differing in the length of the C terminus. Since its discovery in Xenopus laevis in 1998, this novel photopigment has received tremendous interest, but has been very refractory to the many attempts to unravel its photochemical and structural properties. Largely, some insight has been collected in its downstream signaling. Due to its low natural abundance most molecular data have been gathered via recombinant expression in heterologous hosts. A variety of expression hosts has been utilized, but to date only a restricted set of to some extent conflicting data has become available, which we here aim to put into perspective. We first briefly recall the most popular hosts and solubilization and purification approaches reported for GPCRs. Subsequently, a critical overview is presented of the outcome of the various host systems employed for recombinant expression of melanopsins, categorized by host type. These data finally are compiled in a general conclusion, and followed by a critical assessment and potential future directions. PMID- 26850933 TI - Implicit and explicit processing of emotional facial expressions in Parkinson's disease. AB - OBJECTIVE: Besides motor problems, Parkinson's disease (PD) is associated with detrimental emotional and cognitive functioning. Deficient explicit emotional processing has been observed, whilst patients also show impaired Theory of Mind (ToM) abilities. However, it is unclear whether this PD patients' ToM deficit is based on an inability to infer others emotional states or whether it is due to explicit emotional processing deficits. We investigated implicit and explicit emotional processing in PD with an affective priming paradigm in which we used pictures of human eyes for emotional primes and a lexical decision task (LDT) with emotional connoted words for target stimuli. METHOD: Sixteen PD patients and sixteen matched healthy controls performed a LTD combined with an emotional priming paradigm providing emotional information through the facial eye region to assess implicit emotional processing. Second, participants explicitly evaluated the emotional status of eyes and words used in the implicit task. RESULTS: Compared to controls implicit emotional processing abilities were generally preserved in PD with, however, considerable alterations for happiness and disgust processing. Furthermore, we observed a general impairment of patients for explicit evaluation of emotional stimuli, which was augmented for the rating of facial expressions. CONCLUSIONS: This is the first study reporting results for affective priming with facial eye expressions in PD patients. Our findings indicate largely preserved implicit emotional processing, with a specific altered processing of disgust and happiness. Explicit emotional processing was considerably impaired for semantic and especially for facial stimulus material. Poor ToM abilities in PD patients might be based on deficient explicit emotional processing, with preserved ability to implicitly infer other people's feelings. PMID- 26850934 TI - [Scleroderma-like disorders]. AB - The finding of hardening and thickening of the skin is common and can be encountered in immune mediated, metabolic, neoplastic, toxic, genetic diseases, or associated with protein deposits. The lack of Raynaud's phenomenon, capillaroscopic abnormalities, or scleroderma-specific autoantibodies should question the diagnosis of scleroderma and trigger the search for a scleroderma like disorder, for which treatment and prognosis differ. This article gives a review of these disorders and their main characteristics. PMID- 26850936 TI - Xenotransplantation literature update, November-December 2015. PMID- 26850935 TI - Droplet digital PCR combined with minisequencing, a new approach to analyze fetal DNA from maternal blood: application to the non-invasive prenatal diagnosis of achondroplasia. AB - BACKGROUND: Achondroplasia is generally detected by abnormal prenatal ultrasound findings in the third trimester of pregnancy and then confirmed by molecular genetic testing of fetal genomic DNA obtained by aspiration of amniotic fluid. This invasive procedure presents a small but significant risk for both the fetus and mother. Therefore, non-invasive procedures using cell-free fetal DNA in maternal plasma have been developed for the detection of the fetal achondroplasia mutations. METHODS: To determine whether the fetus carries the de novo mis-sense genetic mutation at nucleotide 1138 in FGFR3 gene involved in >99% of achondroplasia cases, we developed two independent methods: digital-droplet PCR combined with minisequencing, which are very sensitive methods allowing detection of rare alleles. RESULTS: We collected 26 plasmatic samples from women carrying fetus at risk of achondroplasia and diagnosed to date a total of five affected fetuses in maternal blood. The sensitivity and specificity of our test are respectively 100% [95% confidence interval, 56.6-100%] and 100% [95% confidence interval, 84.5-100%]. CONCLUSIONS: This novel, original strategy for non-invasive prenatal diagnosis of achondroplasia is suitable for implementation in routine clinical testing and allows considering extending the applications of these technologies in non-invasive prenatal diagnosis of many other monogenic diseases. (c) 2016 John Wiley & Sons, Ltd. PMID- 26850937 TI - Factors That Influence Israeli Muslim Arab Parents' Intention to Vaccinate Their Children Against Influenza. AB - The purpose of the current study was to explore factors related to the intention of parents from the Muslim Arab ethnic minority in Israel to vaccinate their children against influenza, using the Health Belief Model (HBM). DESIGN AND METHODS: This study is a cross sectional quantitative study. A convenience sample of 200 parents of children aged 12 and younger completed a questionnaire based on the HBM. RESULTS: Perceived susceptibility, severity, benefits, and barriers predicted 88% of parents' intention to vaccinate their children. Parents who vaccinated their children in the past year were younger and had fewer children. Community nurses and physicians were identified as important cues to action. CONCLUSIONS: The HBM components predicted a high percentage of parents' intention to vaccinate their children PRACTICE IMPLICATIONS: Interventions to raise vaccination coverage rates among children belonging to an ethnic minority of Israeli Muslim Arabs should begin on the micro level of the parent-health care professional encounter. PMID- 26850938 TI - Comparative spatial genetics and epigenetics of plant populations: heuristic value and a proof of concept. AB - Despite the recent upsurge of interest on natural epigenetic variation of nonmodel organisms, factors conditioning the spatial structure of epigenetic diversity in wild plant populations remain virtually unexplored. We propose that information on processes shaping natural epigenetic variation can be gained using the spatial structure of genetic diversity as null model. Departures of epigenetic isolation-by-distance (IBD) patterns from genetic IBD patterns for the same sample, particularly differences in slope of similarity-distance regressions, will reflect the action of factors that operate specifically on epigenetic variation, including imperfect transgenerational inheritance and responsiveness to environmental factors of epigenetic marks. As a proof of concept, we provide a comparative analysis of spatial genetic and epigenetic structure of 200 mapped individuals of the perennial herb Helleborus foetidus. Plants were fingerprinted using nuclear microsatellites, amplified fragment length polymorphisms (AFLP) and methylation-sensitive AFLP markers. Expectations from individual-level IBD patterns were tested by means of kinship-distance regressions. Both genetic and epigenetic similarity between H. foetidus individuals conformed to theoretical expectations under individual-level IBD models. Irrespective of marker type, there were significant negative linear relationships between the kinship coefficient for plant pairs and their spatial separation. Regression slopes were significantly steeper for epigenetic markers. Epigenetic similarity between individuals was much greater than genetic similarity at shortest distances, such epigenetic 'kinship excess' tending to decrease as plant separation increased. Results suggest that moderate-to-high heritability and responsiveness to local environments are major drivers of epigenetic spatial structure in H. foetidus, and illustrate the heuristic value of comparing genetic and epigenetic spatial structure for formulating and testing hypotheses on forces shaping epigenetic diversity in wild plant populations. PMID- 26850939 TI - Editorial Commentary: Tissue factor expression by the endothelium: Coagulation or inflammation? PMID- 26850940 TI - Validation of a simulator for temporomandibular joint arthroscopy. AB - The traditional method of surgical training has followed the 'observe, practice, and teach' model, which is useful for open surgery, but is insufficient for minimally invasive surgery. This study presents the validation of a new simulator designed for TMJ arthroscopy training. A group of 10 senior maxillofacial surgeons performed an arthroscopy procedure using the simulator. They then completed a questionnaire analyzing the realism of the simulator, its utility, and the educational quality of the audiovisual software. The mean age of the 10 surgeons was 42.6 years, and they had performed a mean 151 arthroscopies. With regard to the realism of the simulator, 80% reported that it was of an appropriate size and design and 70% referred to the very realistic positions and relationships between the internal structures. Regarding its educational potential, 80% reported the simulator to be very useful for acquiring the basic skills and to acquire the sensation of depth during access to the TMJ. Finally, 90% reported the prototype to be very useful for TMJ arthroscopy training. These preliminary results showed a high degree of approval. The general opinion of the group of experts was that the experience was rewarding and inspiring, and that the prototype has the educational potential for the achievement of basic TMJ arthroscopy skills. PMID- 26850941 TI - Home-based HPV self-sampling improves participation by never-screened and under screened women: Results from a large randomized trial (iPap) in Australia. AB - We conducted a randomized controlled trial to determine whether HPV self-sampling increases participation in cervical screening by never- and under-screened (not screened in past 5 years) women when compared with a reminder letter for a Pap test. Never- or under-screened Victorian women aged 30-69 years, not pregnant and with no prior hysterectomy were eligible. Within each stratum (never-screened and under-screened), we randomly allocated 7,140 women to self-sampling and 1,020 to Pap test reminders. The self-sampling kit comprised a nylon tipped flocked swab enclosed in a dry plastic tube. The primary outcome was participation, as indicated by returning a swab or undergoing a Pap test; the secondary outcome, for women in the self-sampling arm with a positive HPV test, was undergoing appropriate clinical investigation. The Roche Cobas(r) 4800 test was used to measure presence of HPV DNA. Participation was higher for the self-sampling arm: 20.3 versus 6.0% for never-screened women (absolute difference 14.4%, 95% CI: 12.6-16.1%, p < 0.001) and 11.5 versus 6.4% for under-screened women (difference 5.1%, 95% CI: 3.4-6.8%, p < 0.001). Of the 1,649 women who returned a swab, 45 (2.7%) were positive for HPV16/18 and 95 (5.8%) were positive for other high-risk HPV types. Within 6 months, 28 (62.2%) women positive for HPV16/18 had colposcopy as recommended and nine (20%) had cytology only. Of women positive for other high risk HPV types, 78 (82.1%) had a Pap test as recommended. HPV self-sampling improves participation in cervical screening for never- and under-screened women and most women with HPV detected have appropriate clinical investigation. PMID- 26850942 TI - Activating transcription factor 3 SUMOylation is involved in angiotensin II induced endothelial cell inflammation and dysfunction. AB - Activating transcription factor 3 (ATF3) is an adaptive-response protein induced by various environmental stresses and is implicated in the pathogenesis of many disease states. However, the role of ATF3 SUMOylation in hypertension-induced vascular injury remains poorly understood. Here we investigated the function of ATF3 SUMOylation in vascular endothelial cells (ECs). The expression of ATF3 and small ubiquitin-like modifier 1 (SUMO1) was increased in angiotensin II (Ang II) induced human umbilical vein endothelial cells (HUVECs). Microscopic analyses further revealed that the expression of ATF3 and SUMO1 is upregulated and colocalized in the endothelium of thoracic aortas from Ang II-induced hypertensive mice. However, Ang II-induced upregulation of ATF3 and SUMO1 in vitro and in vivo was blocked by Ang II type I receptor antagonist olmesartan. Moreover, Ang II induced ATF3 SUMOylation at lysine 42, which is SUMO1 dependent. ATF3 SUMOylation attenuated ATF3 ubiquitination and in turn promoted ATF3 protein stability. ATF3 or SUMO1 knockdown inhibited Ang II-induced expression of inflammatory molecules such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-8. Wild type ATF3 but not ATF3-K42R (SUMOylation defective mutant) reduced the production of nitric oxide (NO), a key indicator of EC function. Consistently, ginkgolic acid, an inhibitor of SUMOylation, increased NO production in HUVECs and significantly improved vasodilatation of aorta from Ang II-induced hypertensive mice. Our findings demonstrated that ATF3 SUMOylation is involved in Ang II-induced EC inflammation and dysfunction in vitro and in vivo through inhibiting ATF3 ubiquitination and increasing ATF3 protein stability. PMID- 26850943 TI - Do stigma and its psychosocial impact differ between Asian-born Chinese immigrants and Western-born Caucasians with head and neck cancer? AB - Stigma appears to influence emotional distress and well-being in cancer survivors, but cross-cultural differences have been ignored. Previous studies suggest that stigma may be especially relevant for survivors of Asian origin. However, their study designs (e.g. focused on female cancers, qualitative designs, and an absence of comparison groups) limit the strength of this conclusion. We hypothesized that (1) Asian-born Chinese immigrants (AI) would report more perceived cancer-related stigma than Western-born Caucasians (WBC); and (2) the impact of stigma on emotional distress and well-being would be greater in AI as compared to WBC. Head and neck cancer survivors (n = 118 AI and n = 404 WBC) completed measures of well-being, emotional distress, and a three item indicator of stigma in structured interviews. The majority of respondents (59%) reported one or more indicators of stigma. Stigma correlated significantly with emotional distress (r = .13, p = .004) and well-being (r = -.09, p = .032). Contrary to our hypotheses, WBCs and AIs did not differ in reported stigma nor did we detect differences in its psychosocial impact. Stigma exerts a deleterious psychosocial impact on head and neck cancer survivors. It did not differ significantly between AI and WBC survivors. PMID- 26850944 TI - Asylum seekers and refugees - how should psychiatry respond? PMID- 26850951 TI - Constipation associated with clozapine: need for closer monitoring. PMID- 26850952 TI - Hallucinations not psychotic? PMID- 26850953 TI - Failure to thrive potentially secondary to maternal venlafaxine use. PMID- 26850968 TI - Impact of Body Mass Index, Age, Prostate Volume, and Genetic Polymorphisms on Prostate-specific Antigen Levels in a Control Population. AB - Prostate-specific antigen (PSA) is still the cornerstone of prostate cancer (PCa) screening and diagnosis in both research and current clinical practice. Inaccuracy of PSA is partly due to the influence of a number of genetic, clinical, and biological factors modifying PSA blood levels. In the present study, we detailed the respective influence of each factor among age, body mass index (BMI), prostate volume, and five single-nucleotide polymorphisms-rs10788160 (10q26), rs10993994 (10q11), rs11067228 (12q24), rs17632542 (19q13.33), and rs2928679 (8p21)-on PSA values in a cohort of 1374 men without PCa. Our results show that genetic factors, when risk variants are combined, influence PSA levels with an effect size similar to that of BMI. Taken together, the respective correlations of clinical parameters and genetic parameters would make it possible to correct and adjust PSA values more effectively in each individual. These results establish the basis to understand and implement a more personalised approach for the interpretation of PSA blood levels in the context of PCa screening and diagnosis. PATIENT SUMMARY: Prostate-specific antigen (PSA) values in an individual may vary according to genetic predisposition. The effect size of this variation can be significant, comparable with those resulting from clinical characteristics. Personalised PSA testing should take this into account. PMID- 26850969 TI - A Critical Analysis of the Current Knowledge of Surgical Anatomy of the Prostate Related to Optimisation of Cancer Control and Preservation of Continence and Erection in Candidates for Radical Prostatectomy: An Update. AB - CONTEXT: In 2010, we published a review summarising the available literature on surgical anatomy of the prostate and adjacent structures involved in cancer control and the functional outcome of prostatectomy. OBJECTIVE: To provide an update based on new literature to help the surgeon improve oncologic and surgical outcomes of radical prostatectomy (RP). EVIDENCE ACQUISITION: We searched the PubMed database using the keywords radical prostatectomy, anatomy, neurovascular bundle, nerve, fascia, pelvis, sphincter, urethra, urinary continence, and erectile function. Relevant articles and textbook chapters published since the last review were critically reviewed, analysed, and summarised. Moreover, we integrated aspects that were not addressed in the last review into this update. EVIDENCE SYNTHESIS: We found new evidence for several topics. Up to 40% of the cross-sectional surface area of the urethral sphincter tissue is laterally overlapped by the dorsal vascular complex and might be injured during en bloc ligation. Denonvilliers fascia is fused with the base of the prostate in a horizontal fashion dorsally/caudally of the seminal vesicles, requiring sharp detachment when preserved. During extended pelvic lymph node dissection, the erectile nerves are at risk in the presacral and internal iliac area. Dissection planes for nerve sparing can be graded according to the amount of tissue left on the prostate as a safety margin against positive surgical margins. Vascular structures can serve as landmarks. The urethral sphincter and its length after RP are influenced by the shape of the apex. Taking this shape into account allows preservation of additional sphincter length with improved postoperative continence. CONCLUSIONS: This update provides additional, detailed information about the surgical anatomy of the prostate and adjacent tissues involved in RP. This anatomy remains complex and widely variable. These details facilitate surgical orientation and dissection during RP and ideally should translate into improved outcomes. PATIENT SUMMARY: Based on recent anatomic findings regarding the prostate and its surrounding tissue, the urologist can individualise the dissection during RP according to cancer and patient characteristics to improve oncologic and functional results at the same time. PMID- 26850971 TI - Re: Craig Rogers, Ravi Barod, Scott Schwartz, Mani Menon. Endovascular Extraction of Caval Tumor Thrombus to Facilitate Minimally Invasive Cytoreductive Nephrectomy for Metastatic Kidney Cancer. Eur Urol 2015;68:167-8. PMID- 26850970 TI - New Clinical Indications for (18)F/(11)C-choline, New Tracers for Positron Emission Tomography and a Promising Hybrid Device for Prostate Cancer Staging: A Systematic Review of the Literature. AB - CONTEXT: Radiolabelled choline positron emission tomography has changed the management of prostate cancer patients. However, new emerging radiopharmaceutical agents, like radiolabelled prostate specific membrane antigen, and new promising hybrid imaging will begin new challenges in the diagnostic field. OBJECTIVE: The continuous evolution in nuclear medicine has led to the improvement in the detection of recurrent prostate cancer (PCa), particularly distant metastases. New horizons have been opened for radiolabelled choline positron emission tomography (PET)/computed tomography (CT) as a guide for salvage therapy or for the assessment of systemic therapies. In addition, new tracers and imaging tools have been recently tested, providing important information for the management of PCa patients. Herein we discuss: (1) the available evidence in literature on radiolabelled choline PET and their recent indications, (2) the role of alternative radiopharmaceutical agents, and (3) the advantages of a recent hybrid imaging device (PET/magnetic resonance imaging) in PCa. EVIDENCE ACQUISITION: Data from recently published (2010-2015), original articles concerning the role of choline PET/CT, new emerging radiotracers, and a new imaging device are analysed. This review is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. EVIDENCE SYNTHESIS: In the restaging phase, the detection rate of choline PET varies between 4% and 97%, mainly depending on the site of recurrence and prostate-specific antigen levels. Both 68gallium (68Ga)-prostate specific membrane antigen and 18F-fluciclovine are shown to be more accurate in the detection of recurrent disease as compared with radiolabelled choline PET/CT. Particularly, Ga68-PSMA has a detection rate of 50% and 68%, respectively for prostate-specific antigen levels < 0.5ng/ml and 0.5 2ng/ml. Moreover, 68Ga- PSMA PET/magnetic resonance imaging demonstrated a particularly higher accuracy in detecting PCa than PET/CT. New tracers, such as radiolabelled bombesin or urokinase-type plasminogen activator receptor, are promising, but few data in clinical practice are available today. CONCLUSIONS: Some limitations emerge from the published papers, both for radiolabelled choline PET/CT and also for new radiopharmaceutical agents. Efforts are still needed to enhance the impact of published data in the world of oncology, in particular when new radiopharmaceuticals are introduced into the clinical arena. PATIENT SUMMARY: In the present review, the authors summarise the last evidences in clinical practice for the assessment of prostate cancer, by using nuclear medicine modalities, like positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging. PMID- 26850972 TI - Effect of Erythropoietin and Stem Cells on Traumatic Brain Injury. AB - OBJECTIVE: To investigate the healing effects of erythropoietin (EPO) and stem cells (SCs) in traumatic brain injury (TBI). METHODS: Twenty-nine Wistar albino rats were used and separated into the following groups: control (C), EPO, SC, and SC+EPO. Group C received a TBI only, with no treatment. In the EPO group, 1000 U/kg EPO was given intraperitoneally at 30 minutes after TBI. In SC group, immediately after formation of TBI, 3 * 10,000 CD34(+) stem cells were injected into the affected area. In the SC+EPO group, half an hour after TBI and the injection of stem cells, 1000 U/kg EPO was injected. Before and after injury, trauma coordination performance was measured by the rotarod and inclined plane tests. RESULTS: Seven weeks after trauma, rat brains were examined by radiology and histology. Rotarod performance test did not change remarkably, even after the injury. Compared with group C, the SC+EPO group was found to have significant differences in the inclined plane test results. CONCLUSIONS: Separately given, SCs and EPO have a positive effect on TBI, and our findings suggest that their coadministration is even more powerful. PMID- 26850973 TI - Microvascular Decompression for Oculomotor Nerve Palsy: A Case Report and Literature Review. AB - BACKGROUND: Oculomotor nerve palsy can result as a manifestation of diabetic mellitus or aneurysmal compression. Vascular loop compression is a very rare etiology of oculomotor nerve palsy. Here, we present a case report of microvascular decompression for oculomotor nerve palsy. CASE DESCRIPTION: We present a 16-year-old male patient, otherwise healthy, who presented with right oculomotor nerve palsy for a period of 1 year. Aneurysmal compression and intracranial lesion were ruled out by cerebral angiogram and magnetic resonance imaging. The presence of vessel loop compression on the nerve was suspected on the basis of features on magnetic resonance imaging. The patient underwent microvascular decompression via a right subtemporal approach. We intraoperatively confirmed vessel loop compression at the exit zone of the nerve from midbrain. Subsequently, the patient's oculomotor palsy has improved gradually over a period of 6 months. CONCLUSIONS: Vascular compression of the oculomotor nerve is a very rare finding in neurosurgical practice. A diagnosis of vascular compression is made by excluding other pathologies and using high-resolution images that visualize the nerve and the offending vessel loop. Microvascular decompression can be an effective treatment method for this condition. PMID- 26850974 TI - Anticoagulation Therapy in Traumatic Brain Injury. AB - BACKGROUND: Optimal anticoagulation therapy (AT) in patients with traumatic brain injury (TBI) is a challenging task and proper management is strongly correlated with clinical outcomes. Only limited data are available on AT after TBI and practical decision making is based on the opinion of experts. This review sought to critically assess different therapeutic options using AT and antiplatelet agents in the perioperative period after TBI. METHODS: A comprehensive review of the literature was performed to summarize relevant data on AT in patients with TBI. RESULTS: Patients with preinjury AT with TBI require emergent neurosurgical treatment and they are also at high risk of developing thromboembolic complications or hematoma expansion. New oral anticoagulants offer a lower incidence of intracranial hemorrhage compared with warfarin. The rate of intracranial hemorrhage during new oral anticoagulants or heparin therapy is significantly lower than that with vitamin K antagonists. PMID- 26850975 TI - World Health Organization Grade II Meningioma: A 10-Year Retrospective Study for Recurrence and Prognostic Factor Assessment. AB - BACKGROUND: We analyzed the characteristics of patients with World Health Organization (WHO) Grade II meningioma to identify factors that may influence recurrence. MATERIALS AND METHODS: Between January 2000 and August 2015, 178 cases of WHO Grade II meningioma were operated at our institution. This population underwent a total of 224 surgical resections, and 36 patients received radiotherapy. Median follow-up was 3.6 years, and interquartile range was 1.5 6.2. RESULTS: A total of 28 patients (16.1%) were re operated for a relapse of their Grade II meningioma. The median time between the first and the second surgery was 4.2 years [interquartile range 1.4-5.3]. Surgical recurrence-free survival at 1, 2, 5, and 10 years were: 96.9% (95% confidence interval [95% CI] 94.2-99.6; 91.7%, 95% CI 87.3-96.3; 85%, 95% CI 78.6-92; and 70.8%, 95% CI 60.1 83.5), respectively. At the end of the study, 93 patients (57.8%) had no residual tumor on the last scan. Age at diagnosis (hazard ratio [HR] 0.17, 95% CI 0.05 0.56, P < 0.001), extent of resection (HR 0.22, 95% CI 0.08-0.64, P = 0.01), and Ki-67 index (HR 0.18, 95% CI 0.06-0.56, P < 0.001) were independent factors associated with the surgical recurrence-free survival. CONCLUSIONS: Younger patients with a lower proliferation rate and gross total resection are less likely to undergo a reintervention for WHO Grade II meningioma recurrence. Observation rather than systematic adjuvant radiotherapy may be preferred. If possible, a redo surgery may be considered in case of relapse or tumor residual progression, because radiotherapy may not decrease the surgical recurrence-free survival after complete or incomplete resection. PMID- 26850976 TI - Antiepileptic use for epilepsy and nonepilepsy disorders: A population-based study (1998-2013). AB - OBJECTIVE: To examine the trends in antiepileptic drug (AED) use among individuals living in Manitoba with and without a history of epilepsy. METHODS: Using data obtained from administrative health databases in Manitoba, we assessed the quarterly prevalence of AED use between 1998 and 2013 among individuals with and without a history of epilepsy using cross-sectional time series analysis. RESULTS: Over the study period, the number of individuals prescribed AEDs increased more than 3-fold, from 8,883 to 27,246. The prevalence of AED use among patients with epilepsy increased by 3%, from 789.6 per 1,000 in 1998/1999 to 813.9 per 1,000 in 2012/2013 (p < 0.001 after 2006). In contrast, we observed a 210% increase in AED use among patients without epilepsy from 6.8 to 21.1 per 1,000 over the same period (p < 0.001). We observed a 55-fold rise in gabapentin use among patients without a seizure disorder (from 0.2 to 11.1 per 1,000; p < 0.001), while gabapentin use among those with epilepsy increased only 2-fold, from 21.6 to 41.3 per 1,000 (p < 0.001). CONCLUSIONS: There has been a marked increase in the prevalence of AED users over the last 15 years, with a large shift towards the use of newer antiepileptic agents (primarily gabapentin) among those without epilepsy. Further research on the effect of these trends on health and economic outcomes will be of interest for clinicians and policymakers. PMID- 26850977 TI - Myasthenia gravis exacerbation after discontinuing mycophenolate: A single-center cohort study. AB - OBJECTIVE: To determine whether discontinuation or marked reduction of mycophenolate mofetil (MMF) in patients with myasthenia gravis (MG) causes MG exacerbations. METHODS: We identified 88 patients with MG who took MMF during the 5-year period 2007-2011 at our MG clinic. We then performed detailed chart reviews and recorded all MG exacerbations and their relationship to MMF and other treatment changes. We also recorded demographic data and disease characteristics (including antibody status and Myasthenia Gravis Foundation of America status). RESULTS: There were 14 patients who had an MG exacerbation during the study period. Of these, 13 had discontinued MMF therapy, with a median time until exacerbation of 16 weeks after discontinuation (9 patients) or marked dose reduction (4 patients) of MMF therapy (exacerbation in the absence of change in any other component of the immunosuppressive regimen). Using the cluster option in a Cox regression analysis, the MMF coefficient was -5.32, with a standard error of 1.05 and a p value of 0.0002, corresponding to an estimated hazard ratio of 204. CONCLUSIONS: This retrospective cohort study suggests that discontinuation/marked reduction of MMF therapy may increase the risk of MG exacerbation many fold, supporting the hypothesis that MMF plays a role in the maintenance of MG remission/minimal manifestation status. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with MG taking MMF, discontinuation or marked reduction of MMF causes MG exacerbation. PMID- 26850978 TI - Incontinence and gait disturbance after intraventricular extension of intracerebral hemorrhage. AB - OBJECTIVE: We tested the hypothesis that intraventricular hemorrhage (IVH) is associated with incontinence and gait disturbance among survivors of intracerebral hemorrhage (ICH) at 3-month follow-ups. METHODS: The Genetic and Environmental Risk Factors for Hemorrhagic Stroke study was used as the discovery set. The Ethnic/Racial Variations of Intracerebral Hemorrhage study served as a replication set. Both studies performed prospective hot-pursuit recruitment of ICH cases with 3-month follow-up. Multivariable logistic regression analyses were computed to identify risk factors for incontinence and gait dysmobility at 3 months after ICH. RESULTS: The study population consisted of 307 ICH cases in the discovery set and 1,374 cases in the replication set. In the discovery set, we found that increasing IVH volume was associated with incontinence (odds ratio [OR] 1.50; 95% confidence interval [CI] 1.10-2.06) and dysmobility (OR 1.58; 95% CI 1.17-2.15) after controlling for ICH location, initial ICH volume, age, baseline modified Rankin Scale score, sex, and admission Glasgow Coma Scale score. In the replication set, increasing IVH volume was also associated with both incontinence (OR 1.42; 95% CI 1.27-1.60) and dysmobility (OR 1.40; 95% CI 1.24-1.57) after controlling for the same variables. CONCLUSION: ICH subjects with IVH extension are at an increased risk for developing incontinence and dysmobility after controlling for factors associated with severity and disability. This finding suggests a potential target to prevent or treat long term disability after ICH with IVH. PMID- 26850979 TI - Integrated systems of stroke care and reduction in 30-day mortality: A retrospective analysis. AB - OBJECTIVE: To evaluate the association between the presence of integrated systems of stroke care and stroke case-fatality across Canada. METHODS: We used the Canadian Institute of Health Information's Discharge Abstract Database to retrospectively identify a cohort of stroke/TIA patients admitted to all acute care hospitals, excluding the province of Quebec, in 11 fiscal years from 2003/2004 to 2013/2014. We used a modified Poisson regression model to compute the adjusted incidence rate ratio (aIRR) of 30-day in-hospital mortality across time for provinces with stroke systems compared to those without, controlling for age, sex, stroke type, comorbidities, and discharge year. We conducted surveys of stroke care resources in Canadian hospitals in 2009 and 2013, and compared resources in provinces with integrated systems to those without. RESULTS: A total of 319,972 patients were hospitalized for stroke/TIA. The crude 30-day mortality rate decreased from 15.8% in 2003/2004 to 12.7% in 2012/2013 in provinces with stroke systems, while remaining 14.5% in provinces without such systems. Starting with the fiscal year 2009/2010, there was a clear reduction in relative mortality in provinces with stroke systems vs those without, sustained at aIRR of 0.85 (95% confidence interval 0.79-0.92) in the 2011/2012, 2012/2013, and 2013/2014 fiscal years. The surveys indicated that facilities in provinces with such systems were more likely to care for patients on a stroke unit, and have timely access to a stroke prevention clinic and telestroke services. CONCLUSION: In this retrospective study, the implementation of integrated systems of stroke care was associated with a population-wide reduction in mortality after stroke. PMID- 26850980 TI - Stroke systems of care: The sum is greater than the parts. PMID- 26850981 TI - Pseudotumoral presentation of cerebral amyloid angiopathy-related inflammation. AB - OBJECTIVE: To identify the clinical and radiologic features that should raise suspicion for the pseudotumoral presentation of cerebral amyloid angiopathy related inflammation (CAA-I). METHODS: We retrospectively reviewed the characteristics of 5 newly diagnosed and 23 previously reported patients in whom the CAA-I imaging findings were initially interpreted as CNS neoplasms. RESULTS: Most cases (85%) occurred in patients >60 years old. The clinical characteristics at presentation included subacute cognitive decline (50%), confusion (32%), focal deficits (32%), seizures (25%), and headaches (21%). Brain MRI demonstrated infiltrative white matter lesions that exhibited a loco-regional mass effect without parenchymal enhancement (93%). In general, these findings were interpreted as low-grade glioma or lymphoma. Eighteen patients (64%) underwent a biopsy, which was nondiagnostic in 4 patients (14%), and 6 patients (21%) underwent a surgical resection. The primary reason for the misinterpretation of the imaging findings was the absence of T2*-weighted gradient recalled echo (T2* GRE) sequences on initial imaging (89%). When subsequently performed (39%), the T2*-GRE sequences demonstrated multiple characteristic cortical and subcortical microhemorrhages in all cases. Perfusion MRI and magnetic resonance spectroscopy (MRS), which were performed on a subset of patients, indicated markedly reduced relative cerebral blood flow and a normal metabolic ratio. CONCLUSION: The identification of one or several nonenhancing space-occupying lesions, especially in elderly patients presenting with cognitive impairment, should raise suspicion for the pseudotumoral presentation of CAA-I and lead to T2*-GRE sequences. Perfusion MRI and MRS appear to be useful techniques for the differential diagnosis of this entity. PMID- 26850982 TI - Oral misoprostol is as safe as Foley catheter for labour induction...or is it? PMID- 26850984 TI - El Nino and climate change--contributing factors in the dispersal of Zika virus in the Americas? PMID- 26850983 TI - Induction of labour at term with oral misoprostol versus a Foley catheter (PROBAAT-II): a multicentre randomised controlled non-inferiority trial. AB - BACKGROUND: Labour is induced in 20-30% of all pregnancies. In women with an unfavourable cervix, both oral misoprostol and Foley catheter are equally effective compared with dinoprostone in establishing vaginal birth, but each has a better safety profile. We did a trial to directly compare oral misoprostol with Foley catheter alone. METHODS: We did an open-label randomised non-inferiority trial in 29 hospitals in the Netherlands. Women with a term singleton pregnancy in cephalic presentation, an unfavourable cervix, intact membranes, and without a previous caesarean section who were scheduled for induction of labour were randomly allocated to cervical ripening with 50 MUg oral misoprostol once every 4 h or to a 30 mL transcervical Foley catheter. The primary outcome was a composite of asphyxia (pH <=7.05 or 5-min Apgar score <7) or post-partum haemorrhage (>=1000 mL). The non-inferiority margin was 5%. The trial is registered with the Netherlands Trial Register, NTR3466. FINDINGS: Between July, 2012, and October, 2013, we randomly assigned 932 women to oral misoprostol and 927 women to Foley catheter. The composite primary outcome occurred in 113 (12.2%) of 924 participants in the misoprostol group versus 106 (11.5%) of 921 in the Foley catheter group (adjusted relative risk 1.06, 90% CI 0.86-1.31). Caesarean section occurred in 155 (16.8%) women versus 185 (20.1%; relative risk 0.84, 95% CI 0.69 1.02, p=0.067). 27 adverse events were reported in the misoprostol group versus 25 in the Foley catheter group. None were directly related to the study procedure. INTERPRETATION: In women with an unfavourable cervix at term, induction of labour with oral misoprostol and Foley catheter has similar safety and effectiveness. FUNDING: FondsNutsOhra. PMID- 26850985 TI - Transcription factor gene GATA2: Association of leukemia and nonsynonymous to the synonymous substitution rate across five mammals. AB - GATA2 gene encodes a member of the GATA family of zinc-finger transcription factors that play a pivotal role during the transition of primitive blood forming cells into white blood cells. Mutation in GATA2 results in the loss of function or even gain of function, including abnormal proliferation of white blood cells that may predispose to acute myeloid leukemia. Our results showed that the codon usage in GATA2 has been influenced by GC mutation bias where nature has highly favored fourteen most over represented codons but disfavored the ATA codon across five mammals. Purifying natural selection has affected GATA2 gene in human and other mammals to maintain its protein function during the period of evolution. Our findings report an insight into the codon usage patterns in gaining the clues for codon optimization to alter the translational efficiency as well as for the functional conservation of gene expression and the significance of nucleotide composition in GATA2 gene within mammals. PMID- 26850986 TI - Periplogenin induces necroptotic cell death through oxidative stress in HaCaT cells and ameliorates skin lesions in the TPA- and IMQ-induced psoriasis-like mouse models. AB - Psoriasis is a multifactorial skin disease that inconveniences many patients. Considering the side effects and drug resistance of the current therapy, it is urgent to discover more effective and safer anti-psoriatic drugs. In the present study, we screened over 250 traditional Chinese medicine compounds for their ability to inhibit the cell viability of cultured human HaCaT keratinocytes, a psoriasis-relevant in vitro model, and found that periplogenin was highly effective. Mechanistic studies revealed that apoptosis and autophagy were not induced by periplogenin in HaCaT cells. However, periplogenin caused PI to permeate into cells, increased lactate LDH release and rapidly increased the number of necrotic cells. Additionally, the typical characteristics of necrosis were observed in the periplogenin-treated HaCaT cells. Notably, the necroptosis inhibitor Nec-1 and NSA were able to rescue the cells from necrotic cell death, supporting that necroptosis was involved in periplogenin-induced cell death. Furthermore, the ROS levels were elevated in the periplogenin-treated cells, NAC (an antioxidant) and Nec-1 could inhibit the ROS levels, and NAC could attenuate necroptotic cell death, indicating that the periplogenin-induced necroptotic cell death was mediated by oxidative stress. More importantly, in the murine models of TPA-induced epidermal hyperplasia and IMQ-induced skin inflammation, topical administration of periplogenin ameliorated skin lesions and inflammation. In sum, our results indicate, for the first time, that periplogenin is a naturally occurring compound with potent anti-psoriatic effects in vitro and in vivo, making it a promising candidate for future drug research. PMID- 26850988 TI - From Resistance to Invitations: How Men Voluntarily in Therapy for Intimate Partner Violence May Contribute to the Development of a Working Alliance. AB - The high drop-out rate and modest outcome for men in treatment for intimate partner violence (IPV) have highlighted the question of how therapists can establish an effective working alliance with these clients. The aim of this study was to conceptualize the variety of ways in which male clients using violence against a female partner might present themselves to form a working alliance that might appeal to them. We studied how 20 men voluntarily in individual IPV treatment contributed at the beginning of therapy to forming an alliance with therapists skilled in such treatment. The first therapy session in 10 drop-out and 10 completed cases was transcribed verbatim and analyzed qualitatively, following guidelines drawn from the constructionist grounded theory. The analysis resulted in a conceptual model of gateways and invitations to an alliance. Gateways are themes that have the potential to open a path toward collaboration on personal change. Each of the three gateways identified, comprised solide and weak invitations to an alliance: (a) presenting reasons for seeking treatment-as their own choice, as avoidance, or as a mistake; (b) presenting notions of change as their own need to change their violent behavior, as ambivalence toward the project, or as a need to change the partner; and (c) disclosing and describing violence-as a personal narrative, as a scene, as a fragment of their life, or as something else. Implications for therapists' understanding of clients' motivational goals, negotiation of alliance, and disclosure of violence early in therapy are discussed. PMID- 26850987 TI - Chk1 inhibitor synergizes quinacrine mediated apoptosis in breast cancer cells by compromising the base excision repair cascade. AB - Quinacrine (QC) causes apoptosis in breast cancer cells by induction of DNA damage, arrest of cells in S-phase, and by topoisomerase inhibition. Here, we show that QC-mediated apoptosis is not only due to increased DNA damage but also by compromising cell cycle checkpoints and base excision repair (BER) capacity in breast cancer cells. QC decreased CHK1, CDKs (CDC2, MDM2, CDC6), cyclins (B1, E1) and CDC25-A in a dose dependent manner. The expression of basal ATR remains unaltered but pATR (Ser-428) increased after QC treatment. A CHK1 inhibitor, SB218078, was also tested alone and in combination with QC. Like QC, SB218078 caused apoptosis by DNA damage and S-phase arrest. The combination of QC and SB218078 increased apoptosis by blocking the cell cycle in G2/M, which caused a mitotic catastrophe, and induced DNA damage at a higher level in comparison to individual compound treatments. Both drugs individually or in combination decreased the levels of replication protein A (RPA). Measurement of the expression of BER (SP- and LP-BER) proteins and direct in vivo BER activity revealed that the QC/SB218078 combination caused apoptosis in cancer cells by disrupting the induction of BER, which represents a novel means of potentially treating breast cancer. PMID- 26850989 TI - A quantitative comparison of the hemispheric, areal, and laminar origins of sensory and motor cortical projections to the superior colliculus of the cat. AB - The superior colliculus (SC) is a midbrain structure central to orienting behaviors. The organization of descending projections from sensory cortices to the SC has garnered much attention; however, rarely have projections from multiple modalities been quantified and contrasted, allowing for meaningful conclusions within a single species. Here, we examine corticotectal projections from visual, auditory, somatosensory, motor, and limbic cortices via retrograde pathway tracers injected throughout the superficial and deep layers of the cat SC. As anticipated, the majority of cortical inputs to the SC originate in the visual cortex. In fact, each field implicated in visual orienting behavior makes a substantial projection. Conversely, only one area of the auditory orienting system, the auditory field of the anterior ectosylvian sulcus (fAES), and no area involved in somatosensory orienting, shows significant corticotectal inputs. Although small relative to visual inputs, the projection from the fAES is of particular interest, as it represents the only bilateral cortical input to the SC. This detailed, quantitative study allows for comparison across modalities in an animal that serves as a useful model for both auditory and visual perception. Moreover, the differences in patterns of corticotectal projections between modalities inform the ways in which orienting systems are modulated by cortical feedback. J. Comp. Neurol. 524:2623-2642, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26850990 TI - The impact of gender, level of amputation and diabetes on prosthetic fit rates following major lower extremity amputation. AB - BACKGROUND: Diabetes mellitus is a leading cause of major lower extremity amputation. OBJECTIVE: To examine the influence of gender, level of amputation and diabetes mellitus status on being fit with a prosthetic limb following lower extremity amputation for peripheral arterial disease. STUDY DESIGN: Retrospective analysis of the Scottish Physiotherapy Amputee Research Group dataset. RESULTS: Within the cohort with peripheral arterial disease ( n = 1735), 64% were men ( n = 1112) and 48% ( n = 834) had diabetes mellitus. Those with diabetes mellitus were younger than those without: mean 67.5 and 71.1 years, respectively ( p < 0.001). Trans-tibial amputation:trans-femoral amputation ratio was 2.33 in those with diabetes mellitus, and 0.93 in those without. A total of 41% of those with diabetes mellitus were successfully fit with a prosthetic limb compared to 38% of those without diabetes mellitus. Male gender positively predicted fitting with a prosthetic limb at both trans-tibial amputation ( p = 0.001) and trans-femoral amputation ( p = 0.001) levels. Bilateral amputations and increasing age were negative predictors of fitting with a prosthetic limb ( p < 0.001). Diabetes mellitus negatively predicted fitting with a prosthetic limb at trans-femoral amputation level ( p < 0.001). Mortality was 17% for the cohort, 22% when the amputation was at trans-femoral amputation level. CONCLUSION: Of those with lower extremity amputation as a result of peripheral arterial disease, those with diabetes mellitus were younger, and more had trans-tibial amputation. Although both age and amputation level are good predictors of fitting with a prosthetic limb, successful limb fit rates were no better than those without diabetes mellitus. Clinical relevance This is of clinical relevance to those who are involved in the decision-making process of prosthetic fitting following major amputation for dysvascular and diabetes aetiologies. PMID- 26850991 TI - Striking difference of periarticular bone density change in early psoriatic arthritis and rheumatoid arthritis following anti-rheumatic treatment as measured by digital X-ray radiogrammetry. AB - OBJECTIVES: To examine changes in hand BMD as measured by digital X-ray radiogrammetry (DXR-BMD) in early PsA compared with RA patients prior to and 3 and 12 months after introducing an antirheumatic treatment. Further, to identify predictors for hand bone loss at the time of disease presentation. METHODS: Recent-onset, active, treatment-naive patients were recruited. Clinical assessment, hand X-rays and DXR were obtained at 0, 3 and 12 months. Mean DXR-BMD for both hands and changes in DXR-BMD (mg/cm(2)/month) were compared between the two groups. We compared baseline disease characteristics of patients with normal hand DXR-BMD with those with bone loss. Logistic regression analyses were performed to identify predictors of hand BMD loss. RESULTS: A total of 64 patients were included. Hand DXR-BMD decreased in RA throughout the study (P = 0.043). Changes in periarticular bone density over 12 months differed between PsA and RA (P = 0.001). Hand bone loss at 3 months was associated with elevated BMI [odds ratio (OR) = 3.59, P = 0.041] and heavier alcohol intake (OR = 1.13, P = 0.035). Diagnosis of RA (OR = 57.48, P = 0.008), heavier alcohol intake (OR = 1.27, P = 0.012) and higher swollen joint count (SJC28) (OR = 1.5, P = 0.036) were independent predictors for hand bone loss in the first year. CONCLUSION: Following treatment, we found ongoing hand bone loss in RA and unchanged periarticular bone density in PsA, supporting the hypothesis that different pathomechanisms are involved in hand bone remodelling in PsA. Presence of RA, heavier alcohol intake and higher SJC were identified as independent predictors for hand bone loss over 1 year. PMID- 26850993 TI - Characterization of functionally active interleukin-18/eGFP fusion protein expression during cell cycle phases in recombinant chicken DF1 Cells. AB - The dependence of foreign gene expression on cell cycle phases in mammalian cells has been described. In this study, a DF1/chIL-18a cell line that stably expresses the fusion protein chIL-18 was constructed and the enhanced green fluorescence protein connected through a (G4 S)3 linker sequence investigated the relationship between cell cycle phases and fusion protein production. DF1/chIL-18a cells (1 * 10(5) ) were inoculated in 60-mm culture dishes containing 5 mL of media to achieve 50%-60% confluence and were cultured in the presence of the cycle specific inhibitors 10058-F4, aphidicolin, and colchicine for 24 and 48 h. The percentage of cell density and mean fluorescence intensity in each cell cycle phase were assessed using flow cytometry. The inhibitors effectively arrested cell growth. The fusion protein production rate was higher in the S phase than in the G0/G1 and G2/M phases. When cell cycle progression was blocked in the G0/G1, S, and G2/M phases by the addition of 10058-F4, aphidicolin, and colchicine, respectively, the aphidicolin-induced single cells showed higher fusion protein levels than did the 10058-F4- or colchicine-induced phase cells and the uninduced control cells. Although the cells did not proliferate after the drug additions, the amount of total fusion protein accumulated in aphidicolin-treated cells was similar to that in the untreated cultures. Fusion protein is biologically active because it induces IFN-gamma production in splenocyte cultures of chicken. (c) 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:581-591, 2016. PMID- 26850992 TI - Interaction of Insulin Resistance and Related Genetic Variants With Triglyceride Associated Genetic Variants. AB - BACKGROUND: Several studies suggest that some triglyceride-associated single nucleotide polymorphisms (SNPs) have pleiotropic and opposite effects on glycemic traits. This potentially implicates them in pathways such as de novo lipogenesis, which is presumably upregulated in the context of insulin resistance. We therefore tested whether the association of triglyceride-associated SNPs with triglyceride levels differs according to one's level of insulin resistance. METHODS AND RESULTS: In 3 cohort studies (combined n=12 487), we tested the interaction of established triglyceride-associated SNPs (individually and collectively) with several traits related to insulin resistance, on triglyceride levels. We also tested the interaction of triglyceride SNPs with fasting insulin associated SNPs, individually and collectively, on triglyceride levels. We find significant interactions of a weighted genetic risk score for triglycerides with insulin resistance on triglyceride levels (Pinteraction=2.73*10(-11) and Pinteraction=2.48*10(-11) for fasting insulin and homeostasis model assessment of insulin resistance, respectively). The association of the triglyceride genetic risk score with triglyceride levels is >60% stronger among those in the highest tertile of homeostasis model assessment of insulin resistance compared with those in the lowest tertile. Individual SNPs contributing to this trend include those in/near GCKR, CILP2, and IRS1, whereas PIGV-NROB2 and LRPAP1 display an opposite trend of interaction. In the pooled data set, we also identify a SNP-by-SNP interaction involving a triglyceride-associated SNP, rs4722551 near MIR148A, with a fasting insulin-associated SNP, rs4865796 in ARL15 (Pinteraction=4.1*10(-5)). CONCLUSIONS: Our findings may thus provide genetic evidence for the upregulation of triglyceride levels in insulin-resistant individuals, in addition to identifying specific genetic loci and a SNP-by-SNP interaction implicated in this process. PMID- 26850994 TI - "Tasting" the cerebrospinal fluid: Another function of the choroid plexus? AB - The choroid plexus (CP) located in brain ventricles, by forming the interface between the blood and the cerebrospinal fluid (CSF) is in a privileged position to monitor the composition of these body fluids. Yet, the mechanisms involved in this surveillance system remain to be identified. The taste transduction pathway senses some types of molecules, thereby evaluating the chemical content of fluids, not only in the oral cavity but also in other tissues throughout the body, such as some cell types of the airways, the gastrointestinal tract, testis and skin. Therefore, we hypothesized that the taste transduction pathway could also be operating in the CP to assess the composition of the CSF. We found transcripts for some taste receptors (Tas1r1, Tas1r2, Tas1r3, Tas2r109 and Tas2r144) and for downstream signaling molecules (alpha-Gustducin, Plcbeta2, ItpR3 and TrpM5) that encode this pathway, and confirmed the expression of the corresponding proteins in Wistar rat CP explants and in the CP epithelial cells (CPEC). The functionality of the T2R receptor expressed in CP cells was assessed by calcium imaging, of CPEC stimulated with the bitter compound D-Salicin, which elicited a rise in the intracellular Ca(2+). This effect was diminished in the presence of the bitter receptor blocker Probenecid. In summary, we described the expression of the taste-related components involved in the transduction signaling cascade in CP. Taken together, our results suggest that the taste transduction pathway in CPEC makes use of T2R receptors in the chemical surveillance of the CSF composition, in particular to sense bitter noxious compounds. PMID- 26850995 TI - Event-related potential correlates of mindfulness meditation competence. AB - OBJECTIVE: This cross-sectional study evaluated event-related potentials (ERPs) across three groups: naive, novice, and experienced meditators as potential physiological markers of mindfulness meditation competence. METHODS: Electroencephalographic (EEG) data were collected during a target tone detection task and a Breath Counting task. The Breath Counting task served as the mindfulness meditation condition for the novice and experienced meditator groups. Participants were instructed to respond to target tones with a button press in the first task (Tones), and then ignore the primed tones while Breath Counting. The primary outcomes were ERP responses to target tones, namely the N2 and P3, as markers of stimulus discrimination and attention, respectively. RESULTS: As expected, P3 amplitudes elicited by target tones were attenuated within groups during the Breath Counting task in comparison to the Tones task (p<.001). There was a task by group interaction for P3 (p=.039). Both meditator groups displayed greater change in peak-to-trough P3 amplitudes, with higher amplitudes during the Tones condition and more pronounced reductions in P3 amplitudes during the Breath Counting meditation task in comparison to the naive group. CONCLUSIONS: Meditators had stronger P3 amplitude responses to target tones when instructed to attend to the tones, and a greater attenuation of P3 amplitudes when instructed to ignore the same tones during the Breath Counting task. This study introduces the idea of identifying ERP markers as a means of measuring mindfulness meditation competence, and results suggest this may be a valid approach. This information has the potential to improve mindfulness meditation interventions by allowing objective assessment of mindfulness meditation quality. PMID- 26850996 TI - Localization of ghrelin-like peptide in the gastrointestinal tract of the golden apple snail (Pomacea canaliculata) and changing of its concentration during fasting. AB - Ghrelin is an endogenous hormone detected in the gastrointestinal tracts (GI) of various species. In the present study, ghrelin-like peptide (ghrelin-LP) was identified in the GI tract of the golden apple snail, Pomacea canaliculata. Using immunohistochemistry, the result revealed an immunoreactivity (-ir) of ghrelin-LP in regions of the GI tract. The ghrelin-LP-ir was observed in both opened-type and closed-type cells of the esophagus, stomach, and small and large intestines. The highest density of ghrelin-LP immunoreactive cells was found in the esophagus and the least density was detected in the stomach. The highest percentages of the opened-type and closed-type cells were present in the esophagus and small intestine, respectively. In immunoblotting, the molecular weight of ghrelin-LP was related to the human ghrelin peptide (~13kDa). Moreover, the concentration of ghrelin-LP was significantly higher in snails that were fasted for 24h compared with fed snails. The concentration decreased after refeeding. The present study could be useful for understanding the physiological role of ghrelin-LP in mollusk species. PMID- 26850998 TI - Skeletal and dental effects of rapid maxillary expansion assessed through three dimensional imaging: A multicenter study. AB - OBJECTIVES: The aim of this study was to determine the skeletal and dental changes in rapid maxillary expansion treatments in two different populations assessed through cone-beam computer tomography (CBCT). MATERIALS AND METHODS: Twenty-one patients from Edmonton, Canada and 16 patients from Cairo, Egypt with maxillary transverse deficiency (11-17 years old) were treated with a tooth-borne maxillary expander (Hyrax). CBCTs were obtained from each patient at two time points (initial T1 and at removal of appliance at 3-6 months T2). CBCTs were analyzed using AVIZO software and landmarks were placed on skeletal and dental anatomical structures on the cranial base, maxilla and mandible. Descriptive statistics, intraclass correlation coefficients and one-way ANOVA analysis were used to determine if there were skeletal and dental changes and if these changes were statistically different between both populations. RESULTS: Descriptive statistics show that dental changes were larger than skeletal changes for both populations. Skeletal and dental changes between populations were not statistically different (P<0.05) from each other with the exception of the upper incisor proclination being larger in the Indiana group (P>0.05). CONCLUSION: Rapid maxillary expansion treatments in different populations demonstrate similar skeletal and dental changes. These changes are greater on the dental structures compared to the skeletal ones in a 4:1 ratio. PMID- 26850997 TI - N-Arylacyl O-sulfonated aminoglycosides as novel inhibitors of human neutrophil elastase, cathepsin G and proteinase 3. AB - The balance between neutrophil serine proteases (NSPs) and protease inhibitors (PIs) in the lung is a critical determinant for a number of chronic inflammatory lung diseases such as chronic obstructive pulmonary disease, cystic fibrosis and acute lung injury. During activation at inflammatory sites, excessive release of NSPs such as human neutrophil elastase (HNE), proteinase 3 (Pr3) and cathepsin G (CatG), leads to destruction of the lung matrix and continued propagation of acute inflammation. Under normal conditions, PIs counteract these effects by inactivating NSPs; however, in chronic inflammatory lung diseases, there are insufficient amounts of PIs to mitigate damage. Therapeutic strategies are needed to modulate excessive NSP activity for the clinical management of chronic inflammatory lung diseases. In the study reported here, a panel of N-arylacyl O sulfonated aminoglycosides was screened to identify inhibitors of the NSPs. Dose dependent inhibitors for each individual serine protease were identified. Select compounds were found to inhibit multiple NSPs, including one lead structure that is shown to inhibit all three NSPs. Two lead compounds identified during the screen for each individual NSP were further characterized as partial mixed inhibitors of CatG. Concentration-dependent inhibition of protease-mediated detachment of lung epithelial cells is demonstrated. PMID- 26851000 TI - Reporting of adherence to healthy lifestyle behaviors among hypertensive adults in the 50 states and the District of Columbia, 2013. AB - Achieving and maintaining a healthy lifestyle is an important part of hypertension management. The purpose of this study was to assess US state-level prevalence of adherence to healthy lifestyle behaviors among those with self reported hypertension. Using 2013 data from the Behavioral Risk Factor Surveillance System, a state-based telephone survey, we examined the adherence to five healthy lifestyle behaviors related to hypertension management: having a "normal" weight, not smoking, avoiding or limiting alcohol intake, consuming the recommended amount of fruits and vegetables, and engaging in the recommended amount of physical activity. We estimated age-standardized percentages of each healthy lifestyle behavior overall and by state, as well as prevalence of all five healthy lifestyle behaviors. Overall, the prevalence of healthy lifestyle behaviors varied widely among those with self-reported hypertension: 20.5% had a normal weight, 82.3% did not smoke, 94.1% reported no or limited alcohol intake, 14.1% consumed the recommended amounts of fruits or vegetables, and 46.6% engaged in the recommended amount of physical activity. Overall, only 1.7% of adults with self-reported hypertension reported all five healthy lifestyle behaviors, with significant variation by state. Age-standardized prevalence of individuals reporting all five healthy lifestyle behaviors ranged from 0.3% in Louisiana to 3.8% in the District of Columbia. In conclusion, adherence to healthy lifestyle behaviors varied among those with hypertension; fewer than 2% reported meeting current recommendations and standards when assessed collectively. Disparities were observed by demographic and descriptive characteristics, including geography. PMID- 26851001 TI - Human Papillomavirus as a Diagnostic and Prognostic Tool in Cancer of Unknown Primary in the Head and Neck Region. AB - Human papillomavirus (HPV) is recognized as a risk factor for oropharyngeal squamous cell carcinomas (SCC), especially tonsillar and base of tongue cancer. Furthermore, HPV-positive tonsillar and base of tongue SCC have a significantly better prognosis than their HPV-negative counterparts and head and neck cancer (HNSCC) in general. HPV has recently also been implicated in cancer of unknown primary (CUP) in the head and neck region, where a primary tumour is not found despite extensive workup. Using fine-needle aspiration cytology to determine CUP HPV status in cervical lymph nodes could be of advantage, since it is minimally invasive and it is assumed that an HPV-positive lymph node metastasis likely has an HPV-positive otopharyngeal SCC origin. We review the current knowledge of HPV in HNSCC, with an emphasis on CUP of the head and neck region, its relation to oropharyngeal, tonsillar and base of tongue SCC and implications of HPV status for diagnosis, prognosis and treatment. PMID- 26851002 TI - Copper Transporter-CTR1 Expression and Pathological Outcomes in Platinum-treated Muscle-invasive Bladder Cancer Patients. AB - BACKGROUND/AIM: Platinum (Pt)-based neoadjuvant chemotherapy (NAC) is the standard-of-care for muscle-invasive bladder cancer (MIBC). However, the survival benefit with NAC is driven by patients with pathological response at cystectomy. Non-responders are subject to adverse effects of Pt, with delay in definitive treatment. Copper transporter receptor 1 (CTR1) plays an important role in Pt uptake and the level of expression may influence Pt sensitivity. We hypothesized that tumor CTR1 expression correlated with pathological outcome. PATIENTS AND METHODS: We identified matched paraffin-embedded tissues from pre-NAC transurethral bladder tumor resection (TURBT) and post-NAC radical cystectomy (RC) specimens in 47 patients with MIBC who received Pt-based NAC. Tumor and adjacent normal tissues were stained with CTR1 antibody. CTR1 expression was determined through immunohistochemistry by two pathologists blinded to the outcome (0=undetectable; 1+=barely detectable; 2+=moderate; and 3+=intense staining). Pathological response was defined as either down-staging to non-MIBC (<=pT1N0M0) or complete pathological response (pT0). Pathological outcome was compared between the CTR1 expression groups. RESULTS: Forty-three percent of TURBT and 41% of RC specimens expressed a CTR1 score of 3+. Forty-four percent of patients had a pathological response to NAC, and 17% had pT0 disease at cystectomy. In both pre-NAC TURBT and post-NAC RC specimens, a CTR1 expression score of 3+ correlated with pathological response (p=0.0076 and p=0.023, respectively). CONCLUSION: This is the first study to demonstrate a correlation between CTR1 tumor expression and pathological outcome in Pt-treated MIBC. These findings suggest that CTR1 expression may be a biomarker for Pt sensitivity. PMID- 26851003 TI - Increased Nicotinamide Phosphoribosyltransferase in Rhabdomyosarcomas and Leiomyosarcomas Compared to Skeletal and Smooth Muscle Tissue. AB - Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step in NAD synthesis and is up-regulated in several human malignancies, including breast, colon, prostate, thyroid, gastric, and several hematopoietic malignancies. In some malignancies, such as gastric, thyroid, and prostate carcinomas, higher NAMPT expression correlates with deeper tumor invasion, increased metastatic potential and chemotherapy resistance. We employed tissue microarray immunohistochemistry to examine NAMPT expression in benign skeletal and smooth muscle, leiomyomas, leiomyosarcomas (graded low-, intermediate-, and high-grade), and spindle, embryonal, pleomorphic, and alveolar rhabdomyosarcomas. We found low to intermediate NAMPT expression in benign tissue, leiomyomas, leiomyosarcomas (low- and intermediate-grades), and spindle cell rhabdomyosarcomas. In contrast, high-grade leiomyosarcomas and embryonal, alveolar, and pleomorphic rhabdomyosarcomas showed high NAMPT expression. Herein we show for the first time that NAMPT is overexpressed in certain sarcoma types and the level of NAMPT expression correlates with tumor behavior. PMID- 26851004 TI - Potential Dual Role of Activating Transcription Factor 3 in Colorectal Cancer. AB - BACKGROUND/AIM: Activating transcription factor 3 (ATF3) is a member of the ATF/CREB transcription factor family and has been proposed as a molecular target for cancer therapy. The present study was undertaken in order to investigate whether ATF3 influences cancer-related phenotypes in colorectal cancer. MATERIALS AND METHODS: ATF3 was overexpressed in human colorectal cancer cells and the effects of ATF3 on apoptosis, cell cycle, cell migration and epithelial mesenchymal transition (EMT) were investigated. B-cell lymphoma-2 (Bcl-2) promoter was cloned and used for luciferase assay in cells transfected with control or ATF3 expression vector. RESULTS: ATF3 down-regulated the expression of Bcl-2 and promoter activity of the Bcl-2 gene. ATF3 increased collective cell migration and expression of cluster of differentiation 44 (CD44) and decreased retinoblastoma (Rb) expression. In addition, ATF3 down-regulated EMT-inducing transcription factors and beta-catenin. CONCLUSION: ATF3 may play a dichotomous role in apoptosis and metastasis in human colorectal cancer cells. PMID- 26851005 TI - Surgical and Oncological Factors Affecting the Successful Engraftment of Patient derived Xenografts in Pancreatic Ductal Adenocarcinoma. AB - BACKGROUND: To effectively use pancreatic cancer patient-derived xenograft (PDX) models in translational research, successful PDX engraftment of surgical specimens in immune-deficient mice is needed. MATERIALS AND METHODS: A total of 102 patients underwent pancreatic cancer resection using various procedures. Tumor tissue from all patents was implanted subcutaneously into mice. Tumor engraftment and growth in mice were determined. Engraftment was tested for correlation with operation type, time, tumor size, and oncogene expression using immunohistoculture. RESULTS: Multivariate analysis showed that a tumor size of more than 3.5 cm in the patient was a significant factor related to successful PDX engraftment. In contrast, there was no correlation of engraftment with surgical procedure, time needed to remove the specimen, tumor differentiation, lymph node metastasis, and protein expression of p53, Receptor tyrosine-protein kinase erbB-2 (CERBB2), or deleted in pancreatic carcinoma locus 4 (DPC4). CONCLUSION: A minimum tumor size in the patient is an important factor for successful tumor engraftment. PMID- 26851006 TI - Molecular Pathways Mediating Metastases to the Brain via Epithelial-to Mesenchymal Transition: Genes, Proteins, and Functional Analysis. AB - BACKGROUND: Brain metastases are the leading cause of morbidity and mortality among patients with disseminated cancer. The development of metastatic disease involves an orderly sequence of steps enabling tumor cells to migrate from the primary tumor and colonize at secondary locations. In order to achieve this complex metastatic potential, a cancer cell is believed to undergo a cellular reprogramming process involving the development of a degree of stemness, via a proposed process termed epithelial-to-mesenchymal transition (EMT). Upon reaching its secondary site, these reprogrammed cancer stem cells submit to a reversal process designated mesenchymal-to-epithelial transition (MET), enabling establishment of metastases. Here, we examined the expression of markers of EMT, MET, and stem cells in metastatic brain tumor samples. MATERIALS AND METHODS: Immunohistochemical analyses were performed to establish the markers of EMT and MET. Co-expression of these markers was determined by immunofluorescence analysis. Gene-expression analysis was conducted using tissues from brain metastases of primary adenocarcinoma of the lung compared to non-metastatic tissue. Cell proliferation was carried out using 3- (4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide S-phase entry analysis, by determining the 5 ethynyl-2'-deoxyuridine incorporation. Scratch wound and chemotactic migration assays were performed in an astrocytic setting. RESULTS: Metastatic brain tumor samples displayed expression of epithelial markers (zinc finger protein SNAI1 and Twist-related protein-1), as well as the mesenchymal marker vimentin. The stem cell marker CD44 was also highly expressed. Moreover, co-expression of the epithelial marker E-cadherin with the mesenchymal marker vimentin was evident, suggesting a state of transition. Expression analysis of transcription factor genes in metastatic brain tumor samples demonstrated an alteration in genes associated with neurogenesis, differentiation, and reprogramming. Furthermore, tumor cells grown in astrocytic medium displayed increased cell proliferation and enhanced S-phase cell-cycle entry. Additionally, chemotactic signaling from the astrocytic environment promoted tumor cell migration. Primary tumor cells and astrocytes were also shown to grow amicably together, forming cell-to-cell interactions. CONCLUSION: These findings suggest that cellular reprogramming via EMT/MET plays a critical step in the formation of brain metastases, where the cerebral milieu provides a microenvironment suitable for the development of metastatic disease. PMID- 26851007 TI - Taurine Attenuates Dimethylbenz[a]anthracene-induced Breast Tumorigenesis in Rats: A Plasma Metabolomic Study. AB - Breast cancer is the most common malignancy and the leading cause of cancer related mortality in women worldwide. Taurine, the most abundant free amino acid, plays a role in several biological processes in humans and has been shown to have activity against breast cancer and other tumors. To investigate the role and mechanism of taurine action in breast cancer, we used dimethylbenz[a]anthracene (DMBA)-induced breast carcinogenesis in rats as a model of breast cancer. The administration of taurine significantly reduced the DMBA-induced breast cancer rate from 80% to 40% in rats (p<0.05). Metabolomic studies using time-of-flight gas chromatography-mass spectrometry identified 23 differential metabolites in the plasma of taurine-administered rats. Bioinformatic analysis further revealed that these metabolites are involved in multiple metabolic pathways, including energy, glucose, amino acid, and nucleic acid metabolism, suggesting that the antitumor activity of taurine in rats is mediated through altered metabolism of breast cancer cells. We propose that these differential metabolites may be potential biomarkers for monitoring cancer therapy and prognosis in the clinic. This study provides a scientific basis for further investigations of the antitumor mechanism of taurine and the development of novel therapeutic strategies to treat breast cancer. PMID- 26851008 TI - Intestinal Tumor Development in C57BL/6J-ApcMin/+ Mice Expressing Human Sulphotransferases 1A1 and 1A2 After Oral Exposure to 2,5-Dimethylfuran. AB - BACKGROUND: 2,5-dimethylfuran (DMF) is formed during heating of foods. Following side chain hydroxylation, DMF could be a substrate for human sulphotransferases (SULTs), which may lead to formation of a DNA reactive electrophile. Only few conflicting in vitro and no in vivo studies on DMF currently exist. MATERIALS AND METHODS: The tumorigenic potential of DMF was studied in multiple intestinal neoplasia Apc(Min/+) (Min) mice that are sensitive to intestinal carcinogenesis and express hSULTs 1A1 and 1A2 (Min/hSULT). Min and Min/hSULT mice were orally exposed to DMF for six weeks. RESULTS: The intestinal tumor development of untreated female Min/hSULT mice was significantly lower compared to that of untreated Min females. No such effects of hSULTs were seen in males. DMF had a weak tumorigenic potential in the colon of female Min/hSULT mice, but not in males. Tumor development in Min mice was not affected. CONCLUSION: Overall, the tumorigenic potential of DMF in a metabolically competent mouse model was not convincing. PMID- 26851009 TI - Restoring Natural Killer Cell Cytotoxicity After Hyperthermia Alone or Combined with Radiotherapy. AB - BACKGROUND: The aim of the present study was to investigate in vitro the effect of hypo- and hyperthermia alone or in combination with irradiation on natural killer cell (NK) cytotoxicity, recovery of this function and the possibility of preventing damage to or enhancing cytotoxicity recovery using interferons (IFNs) alpha, beta, and gamma and interleukin-2 (IL-2). MATERIALS AND METHODS: We used non-selected NK cells and measured their cytotoxicity using the (51)Cr release assay. Temperatures ranging from 31-45 degrees C and thermal treatment times from 0-180 min were assessed. IFNs were applied at concentrations from 0-1,000 IU/ml and IL-2 from 0-450 IU/ml. The range of irradiation dose was from 0-30 Gy. RESULTS: We detected no significant differences in cytotoxicity at temperatures from 31-37 degrees C. The most significant decrease in cytotoxicity was observed between 41 and 42 degrees C (p=0.0010), and heating NK cells at 42 degrees C for 180 min almost completely abolished this function. NK cell cytotoxicity largely recovered during the first 24 h, depending on the heating time. IFN-alpha, beta, and gamma demonstrated no concentration-dependent ability to aid in recovery when used before or after the thermal treatment. In contrast, IL-2 restored cytotoxicity in a concentration- and incubation time-dependent manner and was equally active when used before, during or after heating. NK cells were heated at 42 degrees C for various times and then irradiated with a single dose or first irradiated and then heated; however, no statistically significant differences were observed (p=0.520). An approach of IL-2 treatment followed by radiation and heating was the most effective in restoring NK cytotoxicity (p=0.000). CONCLUSION: NK cell cytotoxicity is impaired in vitro at 42 degrees C and above, with possible partial recovery. IL-2, but not IFNs, was able to restore NK cell cytotoxicity in a concentration-dependent manner. IL-2 can also reverse the damage caused by combined hyperthermia and irradiation. PMID- 26851010 TI - HSV-1 Infection Modulates the Radioresponse of a HPV16-positive Head and Neck Cancer Cell Line. AB - BACKGROUND: The combined effects of Human papillomavirus (HPV) and Herpes simplex type 1 (HSV-1) infections and their effects on cancer cell radioresistance are unexplored. MATERIALS AND METHODS: An HPV16-positive hypopharyngeal carcinoma cell line (UD-SCC-2) was infected with wt-HSV-1 at low multiplicity of infection (MOI) and irradiated with 2 Gy at 24 h postinfection. Viability assays and quantitative reverse-transcriptase PCR for HPV16 E6, E7, nuclear factor kappa B1, B-cell CLL/lymphoma 2 (BCL2), and caspases 3, 8 and 9 at 24, and 72 h, as well as immunocytochemistry for BCL2, caspase 3, cyclin E, mouse double minute 2 homolog (MDM2), HSV-1 and Ki-67 were performed at 144 h postirradiation. RESULTS: At 144 h, cell viability was significantly lowered by irradiation only in uninfected cells. Infection combined with irradiation resulted in increased expression of E6, E7, BCL2 and NF-kappaB1 at 144 h. Simultaneously, E6 and E7 were down regulated in non-irradiated infected cells. Irradiation and infection with 0.00001 MOI separately up-regulated caspase 3 but infection with 0.0001 MOI halved its expression in irradiated cells. CONCLUSION: HSV-1 infection modulates radioresistance of HPV16-positive hypopharyngeal carcinoma cells. PMID- 26851011 TI - Altered Micro-RNA Degradation Promotes Tumor Heterogeneity: A Result from Boolean Network Modeling. AB - Cancer heterogeneity may reflect differential dynamical outcomes of the regulatory network encompassing biomolecules at both transcriptional and post transcriptional levels. In other words, differential gene-expression profiles may correspond to different stable steady states of a mathematical model for simulation of biomolecular networks. To test this hypothesis, we simplified a regulatory network that is important for soft-tissue sarcoma metastasis and heterogeneity, comprising of transcription factors, micro-RNAs, and signaling components of the NOTCH pathway. We then used a Boolean network model to simulate the dynamics of this network, and particularly investigated the consequences of differential miRNA degradation modes. We found that efficient miRNA degradation is crucial for sustaining a homogenous and healthy phenotype, while defective miRNA degradation may lead to multiple stable steady states and ultimately to carcinogenesis and heterogeneity. PMID- 26851012 TI - alpha-Bisabolol Inhibits Invasiveness and Motility in Pancreatic Cancer Through KISS1R Activation. AB - alpha-Bisabolol is a plant-derived, oily sesquiterpene alcohol that induces apoptosis of various cancer cells. We previously reported the antiproliferative effects of alpha-bisabolol on pancreatic cancer cell lines using in vitro and in vivo experiments. However, the effects of alpha-bisabolol on tumor invasiveness and motility are still unknown. In this study, demonstrated that alpha-bisabolol suppressed the invasiveness and motility of a pancreatic cancer cell line. Although Early growth response 1 (EGR1) was involved in antiproliferative effects of alpha-bisabolol, it had no relationship with the inhibitory effect of alpha bisabolol on cellular invasiveness and motility. Polymerase chain reaction analysis revealed that alpha-bisabolol induced Kisspeptin 1 receptor (KISS1R) in pancreatic cancer cell lines. The inhibition of KISS1R weakened the inhibitory effect of alpha-bisabolol on invasiveness of pancreatic cancer cells. The results also implied that the inhibitory effects of alpha-bisabolol on tumor invasiveness and motility are at least partly associated with the activation of KISS1R. However, there is a possibility that other molecular mechanisms of alpha bisabolol regulate invasiveness and motility in pancreatic cancer cells. Further investigations are necessary to clarify the precise mechanisms of alpha-bisabolol activity for clinical application as a novel treatment for pancreatic cancer. PMID- 26851013 TI - Polyphosphate Derived from Lactobacillus brevis Inhibits Colon Cancer Progression Through Induction of Cell Apoptosis. AB - Although probiotics are known to have antitumor activity, few bacteria-derived antitumor molecules have been identified. The present study explored an antitumor molecule derived from Lactobacillus brevis SBL8803 (L. brevis 8803) and the mechanisms that underlie its effects. Cell viability and apoptosis were assessed by a sulforhodamine B assay and terminal deoxynucleotidyl transferase dUTP staining, respectively. Phosphorylated extracellular signal-regulated kinase (ERK) and cleaved poly ADP-ribose polymerase (PARP) expression were detected by western blotting. The conditioned medium of L. brevis 8803 inhibited SW620 cells viability and the effect was reduced by the degradation of polyphosphate (poly P) in the conditioned medium. A xenograft model showed that poly P inhibited the growth of SW620 cells. Poly P induced the apoptosis of SW620 cells through activation of the ERK pathway. In contrast, in primary cultured cells derived from normal mouse, poly P did not affect cell viability. Probiotic-derived poly P is expected to be an antitumor drug with fewer adverse effects than conventional drugs. PMID- 26851014 TI - Polo-like Kinase Inhibitor Volasertib Exhibits Antitumor Activity and Synergy with Vincristine in Pediatric Malignancies. AB - BACKGROUND: Polo-like kinase 1 (PLK1) controls the main cell-cycle checkpoints, suggesting utility of its inhibition for cancer treatment, including of highly proliferative pediatric cancer. This preclinical study explored the selective PLK1 inhibitor volasertib (BI 6727) alone and combined with chemotherapy in pediatric malignancies. MATERIALS AND METHODS: Inhibition of proliferation was explored in vitro using dimethylthiazol carboxymethoxyphenyl sulfophenyl tetrazolium (MTS) assay. Mice bearing human xenografts were treated with weekly intravenous injections of volasertib. RESULTS: Volasertib inhibited proliferation in all 40 cell lines tested, with a mean half-maximal growth inhibitory concentration of 313 nmol/l (range: 4-5000 nmol/l). Volasertib was highly active against RMS-1 alveolar rhabdomyosarcoma xenografts, resulting in 100% tumor regression. Activity was associated with complete and prolonged G2/M arrest and subsequent apoptotic cell death. Volasertib showed synergistic activity with vincristine but antagonistic effects with etoposide. CONCLUSION: These findings support the further exploration of volasertib for pediatric malignancies, particularly alveolar rhabdomyosarcoma, and its combination with mitotic spindle poison. PMID- 26851015 TI - Expression of Submaxillary Gland Androgen-regulated Protein 3A (SMR3A) in Adenoid Cystic Carcinoma of the Head and Neck. AB - BACKGROUND: Adenoid cystic carcinoma of the head and neck (ACC) is a rare tumor entity which originates from the salivary glands. The prognosis remains poor, as the tumor tends to exhibit perineural invasion and frequently develops distant metastases. The submaxillary gland androgen-regulated protein 3A (SMR3A) belongs to a gene family producing opiorphin homologs and is physiologically secreted by salivary glands. Expression of SMR3A has been identified as an unfavorable risk factor in survival of patients with squamous cell carcinoma in the head and neck, but its value as a prognostic biomarker for ACC has not been addressed. MATERIALS AND METHODS: Tissue sections from primary ACC (n=86) and healthy glandular tissue as reference, were stained by immunohistochemistry. SMR3A expression levels were correlated with clinical and pathological features, including overall survival. RESULTS: All patients had undergone surgery and 67 received adjuvant radiotherapy. The median disease-free survival (DFS) was 37 months and the median overall survival (OS) was 75 months. Prominent SMR3A expression in tumor cells was found in 24 of 86 patients (27,9%), and was inversely correlated with a male gender (p=0.009). There was no significant correlation between SMR3A expression and DFS, metastasis-free survival or OS. CONCLUSION: Our data demonstrate for the first time decreased levels of SMR3A in ACC compared to normal glandular tissue. These data suggest a context-dependent regulation of SMR3A expression in the pathogenesis of distinct subtypes of head and neck tumors, and support the assumption that detection of SMR3A expression serves as a surrogate for aberrant differentiation into mucosal- or glandular-like cells in ACC and head and neck squamous cell carcinoma. PMID- 26851017 TI - Development of Stemness in Cancer Cell Lines Resistant to the Anticancer Effects of Zoledronic Acid. AB - BACKGROUND: Drug resistance is closely related to cancer cell stemness, that is acquired along with resistance to various anticancer agents. However, this has not been investigated as a potential mechanism underlying cancer cell resistance to zoledronate, that is used to suppress bone metastasis. MATERIALS AND METHODS: Zoledronate-resistant A549 lung cancer and MG63 osteosarcoma cell lines were established by repeated treatment with sub-lethal concentrations of zoledronate. Expression levels of the stem cell marker NANOG, cMYC, octamer-binding transcription factor 4, and sex-determining region Y-box 2 were evaluated and sphere formation was compared between parental and resistant cell lines. Tumourigenicity was assessed in vivo. RESULTS: Stem cell marker expression was up regulated and sphere formation was enhanced in resistant compared to parental cells and showed greater tumour formation capacity in mice. CONCLUSION: Repeated treatment of malignant tumour cell lines with zoledronate, induces the development of drug resistance and stemness. PMID- 26851016 TI - PLAGL1 (ZAC1/LOT1) Expression in Clear Cell Renal Cell Carcinoma: Correlations with Disease Progression and Unfavorable Prognosis. AB - BACKGROUND: Pleiomorphic adenoma gene-like 1 (PLAGL1) protein was originally shown to induce cell-cycle arrest and promote apoptosis in several types of human tumors and therefore it was considered a candidate tumor suppressor. The involvement of PLAGL1 gene in the etiology and pathogenesis of clear cell renal cell carcinoma (ccRCC) has not been evaluated. The purpose of the present study was to determine the expression level of PLAGL1 in ccRCC and to investigate its potential utility as a prognostic factor. MATERIALS AND METHODS: We applied quantitative real-time polymerase chain reaction (QPCR), western blotting and immunohistochemistry to measure PLAGL1 mRNA/protein contents in paired tumor and kidney specimens of 40 patients with ccRCC. RESULTS: PLAGL1 mRNA and protein levels were increased in tumor tissues as determined by QPCR and immunohistochemistry, respectively. The average content of PLAGL1 protein measured by western blotting did not differ between tumor and non-cancerous kidney tissues. However, increased PLAGL1 protein level in ccRCC tissue positively correlated with the presence of distant metastases and worse patient outcome. CONCLUSION: These results suggest an oncogenic role of PLAGL1 in the progression of ccRCC and its potential value as a prognostic marker. PMID- 26851018 TI - Sensitivity Profiles of Human Prostate Cancer Cell Lines to an 80 Kinase Inhibitor Panel. AB - BACKGROUND: Taxanes and anti-androgen therapies are routinely used for the treatment of metastatic prostate cancer, however the majority of patients eventually develop resistance. MATERIALS AND METHODS: Eighty kinase inhibitors were screened regarding their ability to inhibit cell viability in CWR22, 22Rv1, PC-3 and DU145 prostate cancer cells using automated toxicity assays. Four kinase inhibitors were selected for further investigation. RESULTS: No significant difference in sensitivity patterns was found between the androgen receptor wild type CWR22 and its androgen receptor mutant variant 22Rv1, indicating that androgen receptor mutation did not impact on kinase inhibitor sensitivity in this model. Metastatic PC-3 and DU145 prostate cancer cell lines were less sensitive to kinase inhibitors than the non-metastatic CWR22 and 22Rv1. All four cell lines responded to GSK-3 inhibitor BIO, and MEK inhibitor PD198306. DU145 cells were resistant to p75NTR/TrkA and CHK4 inhibitors, RO-082750 and Ryuvidine. CONCLUSION: Kinase inhibition may be an appropriate strategy for the treatment of prostate cancer. PMID- 26851019 TI - Inhibitory Effects of the Four Main Theaflavin Derivatives Found in Black Tea on Ovarian Cancer Cells. AB - BACKGROUND: Some polyphenols induce apoptosis and inhibit angiogenesis. Consumption of black tea, rich in polyphenols, has been found to reduce ovarian cancer risk. Theaflavin (TF1), theaflavin-3-gallate (TF2a), theaflavin-3'-gallate (TF2b) and theaflavin-3, 3'-digallate (TF3) are four main theaflavin derivatives found in black tea. MATERIALS AND METHODS: Cell proliferation assay, Hoechst 33342 staining assay, Caspase-Glo Assay, western blot, human umbilical vein endothelial cell tube formation assay and vascular endothelial growth factor (VEGF) enzyme-linked immunosorbent assay were performed. RESULTS: All four theaflavin derivatives reduced viability of ovarian cancer cells at lower concentrations than with normal ovarian cells. TF1 mainly mediated apoptosis via the intrinsic pathway, while the others via the intrinsic and extrinsic pathways. TF1 inhibited tube formation via reducing VEGF secretion in a hypoxia-inducible factor 1alpha-independent manner, while the others in a HIF1alpha-dependent way. CONCLUSION: All four theaflavin derivatives inhibited ovarian cancer cells. Some of the effects and mechanisms of TF1 are different from those of the other three theaflavin derivatives. PMID- 26851020 TI - Hypoxic Conditions Promote Gemcitabine Sensitivity in a Pancreatic Cancer Stem Cell Line. AB - Development of an effective therapeutic strategy for refractory pancreatic cancer must consider whether chemosensitivity can be induced in chemoresistant cells. We established a pancreatic cancer stem cell-rich cell line using TIG-1 feeder cells and leukemia inhibitory factor (LIF)-rich SNL76/7 conditioned medium. We generated a cell line, namely YNPC031312-B, following isolation of cells from the malignant ascites of a patient with gemcitabine-resistant pancreatic cancer. A YNPC031312-B-Hypoxia cell line was established by maintaining YNPC031312-B cells under tumor-like hypoxic conditions (1% O2). Both cell lines exhibited a pancreatic cancer stem cell phenotype: YNPC031312-B cells were CD24(+)CD44( )CD133(+)epithelial cell adhesion molecule (EpCAM)(+)alkaline phosphatase(+)Octamer-binding transcription factor (OCT)3/4+and YNPC031312-B Hypoxia cells were CD24(+)CD44(+)CD133(+)EpCAM(+). YNPC031312-B-Hypoxia cells were larger, had superior migratory ability, and higher gemcitabine sensitivity compared to YNPC031312-B cells. The use of LIF or other factors with similar bioactivity under hypoxic conditions may contribute to the phenotypic change to gemcitabine sensitivity. Our results may aid development of new therapeutic strategies targeting refractory pancreatic cancer. PMID- 26851021 TI - Loss of SFRP1 Expression Is Associated with Poor Prognosis in Hepatocellular Carcinoma. AB - BACKGROUND: Secreted frizzled-related protein-1 (SFRP1) is a well-known inhibitor of the wingless type (WNT)-beta-catenin signaling pathway and its inactivation plays an important role in the development and progression of various types of cancer. However, the clinical significance of SFRP1 expression in patients with hepatocellular carcinoma (HCC) remains unknown. MATERIALS AND METHODS: A total of 63 patients with HCC who underwent hepatectomy at our Institution were enrolled in this study. A quantitative real-time polymerase chain reaction (RT-PCR) was performed to determine the SFRP1 mRNA expression level in both the tumorous and non-tumorous tissues of HCC. The patients were divided into low and high gene expression groups based on the SFRP1 gene expression level in their tumor tissues. We analyzed the differences in clinicopathological characteristics between these two groups of patients. RESULT: The expression level of SFRP1 was significantly lower in tumor tissue than in non-tumor tissue (p<0.0001). Significant correlations were observed between a high expression of SFRP1 in tumor tissue and older than 65 years (p=0.030), tumor size less than 5 cm (p=0.011); and no vascular invasion (p=0.004). Patients with high SFRP1 expression in tumor tissue had a significantly better overall survival rate (p=0.040). However, the SFRP1 expression level was not defined as an independent risk factor for patient survival based on results of multivariate analysis. CONCLUSION: SFRP1 may play a role in the development and progression of HCC. Therefore, more studies are required to investigate a potential role of SFRP1 in HCC prognosis. PMID- 26851022 TI - L-Carnosine Prevents the Pro-cancerogenic Activity of Senescent Peritoneal Mesothelium Towards Ovarian Cancer Cells. AB - BACKGROUND/AIM: L-Carnosine inhibits senescence of somatic cells and displays anticancer activity. Here we analyzed if L-carnosine (20 mM) retards senescence of human peritoneal mesothelial cells (HPMCs) and inhibits progression of ovarian cancer cells. MATERIALS AND METHODS: Experiments were performed with primary HPMCs established from patients undergoing abdominal surgery and with three ovarian cancer cell lines: A2780, OVCAR-3 and SKOV-3. RESULTS: L-Carnosine retards senescence of HPMCs plausibly via inhibition of mitochondria-related oxidative stress. Prolonged exposure of HPMCs to L-carnosine prevented senescent HPMC-dependent exacerbation of cancer cell adhesion, migration, invasion and proliferation, which may be linked with decreased secretion of various pro cancerogenic agents by HPMCs. Cancer cells exposed directly to L-carnosine displayed reduced viability, increased frequency of apoptosis and unaltered proliferation. CONCLUSION: L-carnosine may be a valuable anticancer drug, especially in the context of prevention and therapy of intraperitoneal ovarian cancer metastasis. PMID- 26851024 TI - High PTPRQ Expression and Its Relationship to Expression of PTPRZ1 and the Presence of KRAS Mutations in Colorectal Cancer Tissues. AB - BACKGROUND: The risk of sporadic colorectal cancer (CRC) is strongly influenced by Iifestyle, environmental and genetic factors. Protein tyrosine phosphatases belong to a group of enzymes whose role in CRC has not yet been intensively studied. They play an important role in activation/de-activation of many enzymes, influencing cell biology by catalyzing reactions opposing those catalyzed by kinases. Protein tyrosine phosphatase receptor-like type Q (PTPRQ) and protein tyrosine phosphatase receptor-like type Z polypeptide 1 (PTPRZ1) have both been shown to be important in development of many cancer types including CRC. MATERIALS AND METHODS: The expression level of PTPRQ and PTPRZ1 was determined by real-time polymerase chain reaction in 16 CRC tissues obtained from patients diagnosed with adenocarcinoma coli. RESULTS: We revealed a high level of PTPRQ expression (p=0.0080), as well as an association between expression levels of PTPRQ and PTPRZ1 (p<0.0001). Moreover PTPRQ expression was higher in tissues presenting with Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (p=0.0293). CONCLUSION: We confirmed the contribution of PTPRZ1 and especially PTPRQ in CRC development, supporting the hypothesis that PTPRQ is a candidate oncogene, playing a crucial role in phosphorylation/dephosphorylation signaling pathways. PMID- 26851023 TI - Sugar-carrying Polystyrenes Facilitate Harvesting of APCs from MLRs: Possible Application of Sugar-carrying Polystyrenes to Immunotherapy. AB - Antigen-presenting cells (APCs) play a pivotal role in cancer immunotherapy. APCs in conventionally used flasks are harvested by enzymatic digestion or cell scraping for application to cancer immunotherapy. However, these methods may impair functional molecules expressed on the APC surface and reduce their effects in cancer immunotherapy. Recently, we found that APCs could be harvested by shaking at 4 degrees C in flasks coated with poly[N-p-vinylbenzyl-O-2-acetoamide 2-deoxy-beta-D-glucopyranosyl-(1->4)-2-acetoamide-2-deoxy-beta-D-gluconamide] (PVGlcNAc) or a copolymer consisting of sulfonylurea (SU) linked to poly[N-p vinyl-benzyl-4-O-beta-D-galactopyranosyl-D-gluconamide] [P(VLA-co-SU)]. In the present study, we compared the functions of cytotoxic T-lymphocytes (CTLs) induced by APCs generated in PVGlcNAc- or P(VLA-co-SU)-coated flasks and conventional flasks. APCs from PVGlcNAc- or P(VLA-co-SU)-coated flasks showed higher expression of cluster of differentiation (CD)80/86, CD11c, and major histocompatibility complex class II alloantigen I-A(d), and higher cytotoxicity than APCs from conventional flasks. These results suggest that the use of PVGlcNAc- or P(VLA-co-SU)-coated flasks is optimal for harvesting APCs. The generated APCs also have a higher antigen-presenting ability compared to those generated in conventional flasks. Our results may contribute to the development of effective cancer immunotherapies. PMID- 26851025 TI - Antiproliferative and Pro-apoptotic Activities of a Novel Resveratrol Prodrug Against Jurkat CD4+ T-Cells. AB - BACKGROUND/AIM: Resveratrol, a natural polyphenol, possesses many beneficial health properties but its therapeutic application is limited due to its low water solubility and instability against oxidative processes. To improve the stability and lipophilicity of the natural compound, we synthesized a resveratrol prodrug, termed FEHH4-1. In the present study, we compared the antiproliferative and pro apoptotic effects of resveratrol with FEHH4-1 on Jurkat T-cells. MATERIALS AND METHODS: Cell proliferation and viability were monitored by 2,3-bis-(2-methoxy-4 nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay, annexin-V/7-amino actinomycin D staining and western blot. To induce interleukin-2 (IL2) expression, cells were stimulated with phorbol 12-myristate 13 acetate/phytohemagglutinin. IL2 production was quantified by enzyme-linked immunosorbent assay. IL2 promoter activity was studied by a Jurkat T-cell line containing an IL2 promoter luciferase reporter construct. RESULTS: Both polyphenols inhibited proliferation, induced apoptotic cell death and blocked IL2 synthesis in Jurkat T-cells. Most importantly, FEHH4-1 was three-to four-times more potent than resveratrol. CONCLUSION: FEHH4-1 had improved antiproliferative and pro-apoptotic potential against Jurkat T-cells compared to resveratrol. PMID- 26851026 TI - Synergisitic and Antagonistic AML Cell Type-specific Responses to 5-Aza-2 deoxycitidine and 1-h-D-Arabinofuranoside. AB - BACKGROUND: The search for synergistic drug combinations is critical to the treatment of drug-resistant cancer, such as acute myeloid leukemia (AML). Characterizing RNA expression associated with 5-aza-2'-deoxycytidine (DAC) and 1 h-D-arabinofuranosylcytosine (Ara-C) is a critical step to increase the efficacy of their combinatorial therapies. MATERIALS AND METHODS: After 72 h of single dose treatments of AML cells with DAC or Ara-C, the half-maximal effective concentration of DAC and Ara-C and the drug combination index were assessed. RESULTS: Pre-treatment with DAC restores cellular sensitivity in Ara-C-resistant AML cells. In contrast, DAC/Ara-C combinations are antagonistic in other Ara-C sensitive AML cells. CONCLUSION: Our results provide an alternative approach for predicting what combinations, dosing and scheduling of drug delivery should be used to better individualize therapy of AML. PMID- 26851027 TI - ER-Dependent Ca++-mediated Cytosolic ROS as an Effector for Induction of Mitochondrial Apoptotic and ATM-JNK Signal Pathways in Gallic Acid-treated Human Oral Cancer Cells. AB - Release of calcium (Ca(++)) from the endoplasmic reticulum (ER) has been proposed to be involved in induction of apoptosis by oxidative stress. Using inhibitor of ER Ca(++) release dantrolene and inhibitor of mitochondrial Ca(++) uptake Ru-360, we demonstrated that Ca(++) release from the ER was associated with generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, and apoptosis of human oral cancer (OC) cells induced by gallic acid (GA). Small interfering RNA-mediated suppression of protein kinase RNA-like endoplasmic reticulum kinase inhibited tunicamycin-induced induction of 78 kDa glucose regulated protein, C/EBP homologous protein, pro-caspase-12 cleavage, cytosolic Ca(++) increase and apoptosis, but did not attenuate the increase in cytosolic Ca(++) level and apoptosis induced by GA. Ataxia telangiectasia mutated (ATM) mediated c-Jun N-terminal kinase (JNK) phosphorylation and apoptosis by GA was blocked by dantrolene. The specificity of ROS-mediated ATM-JNK activation was confirmed by treatment with N-acetylcysteine, a ROS scavenger. Blockade of ATM activation by specific inhibitor KU55933, short hairpin RNA, or kinase-dead ATM overexpression suppressed JNK phosphorylation but did not completely inhibit cytosolic ROS production, mitochondrial cytochrome c release, pro-caspase-3 cleavage, and apoptosis induced by GA. Taken together, these results indicate that GA induces OC cell apoptosis by inducing the activation of mitochondrial apoptotic and ATM-JNK signal pathways, likely through ER Ca(++)-mediated ROS production. PMID- 26851028 TI - Apolipoprotein E Genotypes in Patients with Prostate Cancer. AB - BACKGROUND: Apolipoprotein E (ApoE) is a potential inhibitor of cell proliferation, immune regulation and modulation of cell growth and differentiation; it also has a substantial role in antioxidant activity. ApoE has a potential role in prostate cancer progression. MATERIALS AND METHODS: ApoE genotyping was performed using real-time polymerase chain reaction (RT-PCR) for blood samples from a group of patients with prostate cancer (n=68) and a control group (n=78). RESULTS: The frequency of the E3/E3 genotype was significantly higher in patients compared to controls (p=0.004). E3/E3 genotype carriers were 3.6-fold more likely to be patients than controls (odds ratio=3.67, 95% confidence interval=1.451-9.155; p=0.004). Additionally, the patients with E3/E3 genotype had significantly higher Gleason score (p=0.017), and more patients with this genotype had a Gleason score higher than 7 (p=0.007). Individuals carrying the E4 allele were significantly more common in the control group (p=0.006). The frequency of the E3/E4 genotype was found to be significantly higher in controls compared to patients (p=0.007), and patients were significantly less likely to have this genotype than controls (odds ratio=0.89, 95% confidence interval=0.833 0.967, p=0.007). Individuals carrying the E2/E3 genotype had a significantly lower Gleason score (p=0.049)-all of the patients with this genotype had a Gleason score lower than 7 (p=0.024). CONCLUSION: E3/E3 genotype may be a potential risk factor for prostate cancer and high Gleason scoring. The E4 allele maybe a risk-reducing factor for prostate cancer. PMID- 26851030 TI - Hypoxia-regulated MicroRNAs in Gastroesophageal Cancer. AB - BACKGROUND/AIM: The present study aimed to identify hypoxia-regulated microRNAs (HRMs) in vitro and investigate the clinical role of candidate HRMs in patients with gastroesophageal cancer (GEC). MATERIALS AND METHODS: microRNA expression changes induced by hypoxia in human GEC cell lines were measured with microarrays and validated by quantitative real-time polymerase chain reaction. Candidate HRMs were measured in pre-therapeutic tumor samples from 195 patients with GEC. RESULTS: Expression of miR-210 was shown to be significantly induced in esophageal squamous cell carcinoma (9.26-fold, p<0.001) and adenocarcinoma cell lines (4.95-fold, p<0.001) and miR-27a-star was significantly up-regulated in adenocarcinoma cell lines (4.79-fold, p=0.04). A weak but significant correlation between miR-210 expression and a 15-gene hypoxia signature was observed (Pearson r correlation: r=0.38, p<0.001). No significant associations of HRMs and clinical outcome in patients with GEC were identified. CONCLUSION: This study supports the involvement of hypoxia on miRNAs in vitro and confirms the role of miR-210 as being a universal HRM. PMID- 26851029 TI - A Phase II Study of BEZ235 in Patients with Everolimus-resistant, Advanced Pancreatic Neuroendocrine Tumours. AB - BACKGROUND: This was a two-stage, phase II trial of the dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor BEZ235 in patients with everolimus-resistant pancreatic neuroendocrine tumours (pNETs) (NCT01658436). PATIENTS AND METHODS: In stage 1, 11 patients received 400 mg BEZ235 orally twice daily (bid). Due to tolerability concerns, a further 20 patients received BEZ235 300 mg bid. Stage 2 would be triggered by a 16-week progression-free survival (PFS) rate of >=60% in stage 1. RESULTS: As of 30 June, 2014, 29/31 patients had discontinued treatment. Treatment-related grade 3/4 adverse events were reported in eight (72.7%) patients at 400 mg and eight (40.0%) patients at 300 mg, including hyperglycaemia, diarrhoea, nausea, and vomiting. The estimated 16-week PFS rate was 51.6% (90% confidence interval=35.7-67.3%). CONCLUSION: BEZ235 was poorly tolerated by patients with everolimus-resistant pNETs at 400 and 300 mg bid doses. Although evidence of disease stability was observed, the study did not proceed to stage 2. PMID- 26851031 TI - Treatment Results of Radiotherapy Combined with Balloon-occluded Arterial Infusion Chemotherapy for Invasive Bladder Cancer. AB - AIM: We present preliminary results from our clinical study evaluating the effectiveness of combination of radiotherapy with balloon-occluded arterial infusion (BOAI) and hemodialysis (HD) for bladder cancer. PATIENTS AND METHODS: We investigated 134 patients with a median age of 67 years (range=38-88 years) and a median follow-up time of 31 months. According to the UICC classification, 89 patients were at clinical stage T2, 40 at T3, and 5 at T4. All patients received external-beam radiation therapy (EBRT) of 50 Gy to the whole pelvis with 10 Gy to the bladder as a boost. During EBRT, BOAI of cisplatin (CDDP) (100 mg/body) was administered from bilateral internal iliac arteries with simultaneous HD to prevent back-flow of CDDP into the systemic circulation. RESULTS: Three-year local control and overall survival (OS) rates were 68% and 80%, respectively, and 3-year bladder preservation rate was 90%. Univariate and multivariate analysis showed that T stage and primary effect were significant prognostic factors for OS. In addition, primary effect was a significant prognostic factor for bladder preservation. None of the patients had grade 2 or more severe hematological toxicity. Late grade >=3 genitourinary (GU) and gastrointestinal (GI) complications were observed in 6% and 2% of the patients, respectively. CONCLUSION: Combination of radiotherapy with BOAI and HD, associated with reduced hematological toxicity, may be regarded as a curative therapy for patients with bladder cancer. Late GU and GI complications were within acceptable limits. T stage is an important predictive factor for the outcome of this therapy. PMID- 26851032 TI - Radiochemotherapy with Gemcitabine in Unresectable Extrahepatic Cholangiocarcinoma: Long-term Results of a Phase II Study. AB - PURPOSE: To evaluate the outcome of patients affected by unresectable extrahepatic cholangiocarcinoma treated with radiotherapy (ERT) and concurrent gemcitabine-based chemotherapy with or without intraluminal brachytherapy (BT). PATIENTS AND METHODS: Twenty-seven patients underwent weekly gemcitabine (100 mg/m(2)) as a 24-h infusion during the course of three-dimensional radiotherapy (50.4 Gy to the tumor and 39.6 Gy to the nodes). Among them, certain patients received a boost of intraluminal high-dose rate (HDR) brachytherapy with 192 Ir. The outcome of patients was evaluated in terms of response to therapy, local control (LC), overall survival (OS) and toxicity. RESULTS: We analyzed a total of 27 patients with the diagnosis of unresectable, non-metastatic adenocarcinoma of the extrahepatic biliary ducts, treated with radiochemotherapy with gemcitabine. After a dose of 50 Gy, a boost of HDR intraluminal brachytherapy was administered in 6 patients (22%): 4 patients received 15 Gy and 2 patients 20 Gy. With a median follow-up of 16 months (range=3-52 months), for the entire group, 2-year LC was 29% (median=12 months), 2-year MFS was 36% (median 16 months). Two-year and three-year OS were 27% and 7% respectively, with a median of 14 months. Toxicities were acceptable. Median OS in patients treated with brachytherapy boost was 21 months versus 14 months for the group treated with gemcitabine-based radiochemotherapy only; 2-year LC was 53% versus 25%, respectively. CONCLUSION: Gemcitabine appears to be a potent radiation sensitizer, and when combined with radiation therapy, it shows encouraging tumor response. Moreover, patients treated with a boost of brachytherapy after radiochemotherapy seem to have a better local control with an acceptable toxicity. Further investigation is warranted to confirm these data and define the optimal combined treatments. PMID- 26851033 TI - A Feasibility Study of Neoadjuvant XELOX Without Radiotherapy for Locally Advanced Lower Rectal Cancer. AB - AIM: This study was planned to evaluate the efficacy and safety of preoperative capecitabine and oxaliplatin (XELOX) without radiation in patients with locally advanced lower rectal cancer. PATIENTS AND METHODS: Patients with clinical stage II/III lower rectal cancer underwent three cycles of XELOX followed by radical surgery. The primary end-point was the R0 resection rate. RESULTS: Thirty-one patients were recruited between February 2012 and August 2014. The completion rate of neoadjuvant chemotherapy was 96.5% among the 29 patients who received it; the remaining two refused chemotherapy and underwent immediate surgery. Grade 3-4 adverse events occurred in nine patients (31%). All 29 patients who received chemotherapy underwent radical resection. The R0 resection rate was 96.5% among these 29 patients. Pathological complete responses were achieved in three patients (10.3%) and downstaging occurred in 13 (44.8%). CONCLUSION: This pilot study found that neoadjuvant XELOX for locally advanced lower rectal cancer is feasible and safe. This neoadjuvant treatment improved resection margin status. PMID- 26851034 TI - Gene-expression Classifier in Papillary Thyroid Carcinoma: Validation and Application of a Classifier for Prognostication. AB - BACKGROUND: No reliable biomarker for metastatic potential in the risk stratification of papillary thyroid carcinoma exists. We aimed to develop a gene expression classifier for metastatic potential. MATERIALS AND METHODS: Genome wide expression analyses were used. Development cohort: freshly frozen tissue from 38 patients was collected between the years 1986 and 2009. Validation cohort: formalin-fixed paraffin-embedded tissues were collected from 183 consecutively treated patients. RESULTS: A 17-gene classifier was identified based on the expression values in patients with and without metastasis in the development cohort. The 17-gene classifier for regional/distant metastasis identified was tested against the clinical status in the validation cohort. Sensitivity for detection of metastases was 51.5% and specificity 61.6%. Log-rank testing failed to identify any significance (p=0.32) regarding the classifier's usefulness as a prognostic marker for recurrence. CONCLUSION: A 17-gene classifier for metastatic potential was developed, and the results showed a clear biological difference between groups. However, through validation, no prognostic significance of this classifier was shown. PMID- 26851035 TI - High NEK2 Expression Is a Predictor of Tumor Recurrence in Hepatocellular Carcinoma Patients After Hepatectomy. AB - BACKGROUND/AIM: Better prognosis of cancer including hepatocellular carcinoma (HCC) remains unsatisfactory due to recurrence and chemoresistance. In this respect it is important to identify molecular targets specific to the disease in order to design effective therapeutic strategies. In the present study, we investigated the prognostic role of Never-in-mitosis-A-related kinase 2 (NEK2) in HCC. MATERIALS AND METHODS: Fifty HCC patients who underwent hepatectomy were enrolled in the study. NEK2 gene and protein expression was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively. RESULTS: Higher expression of NEK2 was detected in HCC tumoral compared to adjacent non-tumor tissues (p<0.001), and protein expression was also relatively high in tumor than corresponding non-tumor tissues. Furthermore, high NEK2 expression was positively correlated with hepatic venous invasion (p=0.047), des-gammacarboxy prothrombin (p=0.003), and alpha fetoprotein (AFP) (p=0.024). Patients with high NEK2 expression had significantly poor recurrence-free survival (p=0.042) and early recurrence. CONCLUSION: Overall, these results suggest that NEK2 could be a promising biomarker for HCC recurrence. PMID- 26851036 TI - Influence of Local Recurrence and Distant Metastasis on Prognosis After Local Excision of Rectal Carcinoma. AB - BACKGROUND: Influence of local recurrence (LR) on prognosis after a local excision (LE) for rectal cancer is unclear. PATIENTS AND METHODS: A total of 152 patients were retrospectively assigned to one of three groups: Groups 1 and 2: complete and incomplete resection respectively, for low-risk carcinoma; group 3: high-risk carcinoma. We evaluated LR, distant metastasis (DM), overall survival, and cancer-specific survival (CSS). RESULTS: LR rates were 10.4%, 43% and 29% for groups 1-3, respectively (p=0.002). In all three groups, DM incidence was low in patients without LR, but high in patients with LR (p<0.0001). Prior LR was an important risk factor for DM (hazard ratio: 14.1, 95% confidence interval=4.3 45.8, p<0.0001). DM significantly reduced CSS. CONCLUSION: There is a strong association between LR and DM independently in the cause of LR. Avoiding LE for high-risk carcinoma and complete LE of low-risk carcinoma are essential to reduce LR and DM. PMID- 26851037 TI - Giant Cavernous Hepatic Hemangioma Diagnosed Incidentally in a Perimenopausal Obese Female with Endometrial Adenocarcinoma: A Case Report. AB - Hemangiomas are the most common benign tumors of the liver, considered giant when they exceed 50-100 mm in diameter. In the present report, we present a case of a 5.2-kg hemangioma of the right hepatic lobe, with hemangiomatous foci in the left lobe, which was incidentally diagnosed in a 53-year-old obese female hospitalized for uterine bleeding. The computed tomographic scan and physical examination revealed a giant abdominal tumor and hepatic hemangioma of the right hepatic lobe was suspected. Right hepatectomy and total hysterectomy with bilateral ovariectomy was performed. The histological examination of the surgical specimens confirmed the extremely giant cavernous hepatic hemangioma, and a synchronous pT1a endometrioid endometrial adenocarcinoma was also diagnosed. The patient remains alive without postoperative disorders, 6 months after surgery. To our knowledge, this is the first reported case of such huge hemangioma incidentally diagnosed in an obese female, with a synchronous endometrial adenocarcinoma of the uterus. Because obesity may cause hyperestrogenism, it might both increase the growth rate of hemangioma and the genesis of endometrial cancer in perimenopausal females. PMID- 26851038 TI - The Role of TPS and TPA in the Diagnostics of Distant Metastases. AB - AIM: The aim of the study was to assess the degree to which tissue polypeptide antigen (TPA) and tissue polypeptide-specific antigen (TPS), as well as carcinoembryonic antigen (CEA), can assist in the detection of distant metastases. PATIENTS AND METHODS: We assessed 157 patients with colorectal and breast cancer divided into two groups. The first was a group of patients with cancer at stages 1, 2 and 3; the second was a group of patients with cancer at stage 4 with metastasis. RESULTS: We found significantly higher levels of all biomarkers in the metastatic group compared to the group with cancer at stages 1 3 (p<0.0001). The calculated area under the receiver operating characteristic (ROC) curve was 0.9929 for TPS, 0.9337 for TPA and 0.7234 for CEA. The cut-off was calculated for each biomarker at 95% specificity, TPS cut-off=255 IU/l (sensitivity 95%), TPA cut-off=200 IU/l (sensitivity 70%) and CEA cut-off=18 MUg/l (sensitivity 37%). CONCLUSION: We suggest combining CEA with TPS or TPA in the detection of distant metastases or using only cytokeratins. This approach can significantly increase the quality of detection of the metastatic process. PMID- 26851039 TI - Nipple-sparing Mastectomy in Patients with Preoperative Diagnosis of Non-invasive Breast Carcinoma. A Single-center Experience. AB - BACKGROUND: Nipple-sparing mastectomy (NSM) is a recognized treatment for selected patients with breast cancer (BC). Our study aimed to analyze 7 years' experience in NSM and breast reconstruction for patients with preoperative diagnosis of non-invasive BC. PATIENTS AND METHODS: All NSMs with breast reconstruction, performed between January 2007 and December 2013 in patients with preoperative diagnosis of non-invasive BC, were considered. RESULTS: Thirty-five NSMs were performed, 23 cases confirming the diagnosis of non-invasive BC, and in 12 patients it also resulted in findings of an invasive component. Patients were stratified into two groups: breast reconstruction was performed i) with silicone definitive implant, ii) with a temporary breast tissue expander. An invasive component at the postoperative histological examination was significantly associated with tissue expander reconstruction (p=0.03). CONCLUSION: In selected cases, NSM is a valid and safe procedure. Further critical evaluations are required for more evidence on this argument. PMID- 26851040 TI - Risk Factors Associated with Disease Recurrence in Patients with Stage III/IV Squamous Cell Carcinoma of the Oral Cavity Treated with Surgery and Postoperative Radiotherapy. AB - AIM: The purpose of the present study was to identify variables associated with high risk of failure in patients with locally advanced squamous cell carcinoma of the oral cavity (SCC-OC). PATIENTS AND METHODS: This retrospective study included 191 patients with stage III-IVb SCC-OC treated with post-operative radiotherapy (RT) or chemoradiotherapy (CRT) between 1995 and 2013. Disease-free (DFS) and overall survival (OS) were analyzed; variables associated with inferior DFS were identified. RESULTS: Seventy-five patients (39%) recurred. DFS and five-year OS were 52% and 54%, respectively. Poorly differentiated tumors (p=0.03), recurrent tumors (p=0.02) and high nodal ratio (p=0.02) were associated with an increased risk of recurrence. CRT was associated with improved DFS in patients with positive margins and/or extracapsular extension (p=0.021). CONCLUSION: Tumors that are recurrent, high grade, or have high nodal ratio are at risk of recurrence. Presence of these disease features should be taken into consideration for better risk stratification. PMID- 26851041 TI - Predictors of Benign Status in Liver Tumors Under 3 cm in Diameter Misdiagnosed as Hepatocellular Carcinoma. AB - BACKGROUND: The clinical features of benign liver lesions misdiagnosed as hepatocellular carcinoma have not been fully described. PATIENTS AND METHODS: This study included 187 patients who underwent hepatectomy at the Kyushu University Hospital following a diagnosis of solitary HCC of <=3 cm in diameter. RESULTS: Following hepatectomy, 9.6% patients were pathologically diagnosed with benign liver lesions. Univariate analysis showed that patient age <=67 years, negativity for hepatitis C virus antigen, lesion size <=1.5 cm, normal level of tumor markers, and absence of increase in tumor size were associated with benign lesions. Patient age <=67 years and absence of tumor size increase were independent predictors of benign lesions. CONCLUSION: Benign liver lesions misdiagnosed as HCC were not infrequent, accounting for approximately 10% of resected cases. Age <=67 years and absence of tumor size increase were independent predictors of benign liver lesions, and may help in the correct diagnosis of HCC. PMID- 26851042 TI - Prognostic Significance of Preoperative Urine Cytology in Low-grade Non-muscle invasive Bladder Cancer. AB - AIM: To examine the clinical significance of preoperative urine cytology in patients with low-grade bladder cancer. PATIENTS AND METHODS: We retrospectively investigated the records of 155 patients diagnosed with primary low-grade (Ta) urothelial carcinoma of the bladder between January 2000 and September 2014. RESULTS: Patients with class III or greater cytology had significantly higher grade (G2) (p=0.01), larger tumors (>=15 mm, p=0.0009) and significantly shorter recurrence-free survival compared to patients with class II or lower cytology (p<0.0001). However, Cox proportional hazards analysis for recurrence-free survival only identified tumor size (>=15 mm) (hazard ratio=5.97, 95% confidence interval=2.39-17.29; p<0.0001) as a predictor of poor prognosis, although patients with class III or higher preoperative cytology showed a tendency towards frequent intravesical recurrence (hazard ratio=1.98, 95% confidence interval=0.96 4.2; p=0.063). CONCLUSION: Preoperative urine cytology, in addition to tumor size, might be a useful predictor of intravesical recurrence of bladder cancer. PMID- 26851043 TI - Karnosky Performance Score and Radiation Dose Predict Survival of Patients Re irradiated for a Locoregional Recurrence of Small Cell Lung Cancer. AB - AIM: When patients with small cell lung cancer (SCLC) experience locoregional recurrence, surgery is often not employed as salvage therapy. Systemic chemotherapy and radiotherapy are often used. Many radiation oncologists are reluctant to deliver a second course of radiotherapy. However, select patients may benefit from re-irradiation. This study aimed to identify these patients. PATIENTS AND METHODS: In patients receiving re-irradiation for a locoregional recurrence of SCLC, 11 potential prognostic factors were analyzed for survival. RESULTS: Survival was positively associated with a Karnofsky performance score >=80 (p=0.003) and a cumulative dose >90 Gy (p=0.026). A trend was observed for younger age, longer interval between first course of radiotherapy and re irradiation, a greater dose of re-irradiation and for concurrent chemotherapy. CONCLUSION: Significant predictors of survival in patients re-irradiated for a locoregional recurrence of SCLC were identified. Patients with a good performance status can benefit from re-irradiation if administered in sufficient doses. PMID- 26851044 TI - Impact of Body Weight Loss on Recurrence After Curative Gastrectomy for Gastric Cancer. AB - BACKGROUND: This study was designed to assess the prognostic role of body weight loss (BWL) after curative gastrectomy for gastric cancer patients. PATIENTS AND METHODS: We analyzed a total of 102 consecutive patients who underwent curative gastrectomy for stage II or III gastric cancer between 2005 and 2011. Postoperative BWL during the first 6 months in patients was calculated from their hospital records. RESULTS: Postoperative BWL was significantly higher in patients with tumours in the upper stomach, total gastrectomy, or subsequent recurrence. A postoperative BWL of 12% was the optimal cut-off value, which was strongly associated with subsequent recurrence. Patients with a postoperative BWL of 12% or higher did not have poorer overall survival but did have significantly poorer disease-free survival than patients with BWL of less than 12%. Cox proportional hazard analyses revealed that a postoperative BWL of 12% or higher was an independent prognostic factor of poor disease-free survival. CONCLUSION: High BWL after curative gastrectomy is related to recurrence in patients with gastric cancer. PMID- 26851045 TI - The Usefulness of Diffusion MRI in Detection of Lymph Node Metastases of Colorectal Cancer. AB - The aim of this study was to assess the sensitivity and specificity of preoperative diagnosis by diffusion magnetic resonance imaging (D-MRI) for lymph node metastasis of colorectal cancer. The b-value represents the diffusion factor (measured in s/mm(2)) and the strength of the diffusion gradients. The b-value used in this study was 1,000 s/mm(2). A total of 119 patients underwent D-MRI before resection of primary colorectal cancer (52 of the rectum, 67 of the colon) at our hospital between February 2005 and April 2006. Lymph node metastases judged by D-MRI were compared with postoperative pathological results. The form of lymph node metastasis was classified either as abundant or scarce type. The predictive values for lymph-node metastasis (sensitivity and specificity) by D MRI were calculated from the result of this classification and lymph-node size. The study was divided into two periods: before the consensus meeting in January 2006, (n=79) (P-I), and after the adjustment of the criteria to improve the sensitivity and specificity based on the results of P-I (n=40) (P-II). Detection of lymph node metastasis using D-MRI in P-I had sensitivity of 61%, specificity of 73%, positive predictive value (PPV) of 55%, and negative predictive value (NPV) of 77%, while in P-II, these values improved to 79%, 95%, 94%, and 83%, respectively. Specificity and PPV for P-II were significantly higher than those for P-I (p<0.05). The diameter of lymph nodes judged to be metastatic on D-MRI (P I vs. P-II: n=32 vs. 16) was 10.3+/-5.4 (3-28) vs. 9.1+/-3.0 (4-14) mm; 11.5+/ 6.2 (4-28) vs. 9.2+/-3.1 (4-14) mm for truly positive nodes (n=18 vs. 15), and 6+/-3.8 (3-14) vs. 8 mm for false-positive nodes (n=14 vs. 1). On the other hand, lymph nodes judged negative by D-MRI (n=47 vs. 24) was 5.9+/-2.4 (3-16) vs. 5.7+/ 2.8 (2-15) mm; 5.9+/-2.1 (3-16) vs. 5.3+/-2.1 (2-8) mm for truly negative (n=36 vs. 20), and 5.7+/-2.7 (3-12) vs. 7.8+/-4.9 (4-15) mm for false negative (n=11 vs. 4). As to the form of metastasis, all truly positive nodes were of the abundant type, and 6/11 (55%) in P-I and 1/4 (25%) in P-II false-negatives were of the scarce type. In conclusion, D-MRI seems useful for preoperative detection of metastatic lymph nodes in colorectal cancer, especially if the node is hyperintense and more than 9 mm in diameter. PMID- 26851046 TI - Orbital Apex Syndrome Caused by Invasive Aspergillosis as an Adverse Effect of Systemic Chemotherapy for Metastatic Colorectal Cancer: a Case Report. AB - Continuous therapy with cytotoxic drugs suppresses humoral immune function and may result in local infection. We present a case of orbital apex syndrome caused by Aspergillus infection during chemotherapy for metastatic colorectal cancer. A 74-year-old man with colorectal liver metastases under long-term continuous systemic chemotherapy presented with painful, progressive orbital apex syndrome. Magnetic resonance imaging disclosed a small enhancing lesion around the right ethmoid sinus. We initially diagnosed colorectal cancer metastasis and he underwent biopsy via the endoscopic endonasal transethmoid approach. However, pathological examination of the cultured specimen revealed Aspergillus fumigatus. The patient was treated with voriconazole and the orbital apex syndrome resolved after 1 month. Orbital aspergillosis is a life-threatening disease and should be listed as a differential diagnosis of uncommon local infections during continuous chemotherapy. PMID- 26851047 TI - Stereotactic Body Radiation Therapy (SBRT) for Recurrent Non-small Cell Lung Cancer (NSCLC). AB - AIM: For local recurrence of non-small cell lung cancer (NSCLC), stereotactic body radiation therapy (SBRT) has become increasingly popular. Many patients with recurrent NSCLC are unable to receive high-dose SBRT [biologically effective dose (BED) >100 Gy] due to poor performance status and potential normal tissue damage. PATIENTS AND METHODS: Thirty-one patients receiving lower-dose SBRT with a BED of 57.6 to 96.0 Gy, were analyzed for local control, freedom from distant progression and survival. RESULTS: In the entire series, local control rates were 96% at 1, 2 and 3 years. Freedom from distant progression rates were 74%, 65% and 65%, respectively, and survival rates were 87%, 65% and 65%, respectively. On multivariate analysis, freedom from distant progression was significantly associated with absence of distant metastases (p=0.009), and survival with BED >75 Gy (p=0.039). CONCLUSION: SBRT with BED <100 Gy provided very promising outcomes when administered for recurrent NSCLC. A BED >75 Gy is recommended, which was superior to lower doses. PMID- 26851048 TI - Neoadjuvant Chemotherapy with Divided-dose Docetaxel, Cisplatin and Fluorouracil for Patients with Squamous Cell Carcinoma of the Esophagus. AB - BACKGROUND: The aim of this phase II study was to evaluate the feasibility of a neoadjuvant chemotherapy regimen consisting of divided-dose docetaxel and cisplatin, with 5-fluorouracil (NAC-DCF), for treatment of patients with stage II/III squamous cell carcinoma of the esophagus (SCCE). PATIENTS AND METHODS: The NAC-DCF regimen, consisting of 2-h infusion of docetaxel at 35 mg/m(2) on days 1 and 8, 4-h infusion of cisplatin at 12 mg/m(2) on days 1-5, and continuous infusion of 5-fluorouracil at 600 mg/m(2) on days 1-5, was administered. We compared NAC-DCF with conventional NAC-CF. RESULTS: The DCF group comprised of 45 patients, and the CF group comprised of 28 patients. The incidence of grade 3/4 neutropenia was significantly higher in the DCF group (56%) than in the CF group (0%). Grade 2/3 pathological response was attained in a significantly higher percentage of patients in the DCF group (40%) than in the CF group (11%) (p=0.0153). CONCLUSION: This DCF regimen led to a high frequency of pathological responses among patients with advanced SCCE. PMID- 26851049 TI - Errata. PMID- 26851050 TI - Developing and Testing a Vaginal Delivery Safety Checklist. AB - Communication failures are the most common root causes of perinatal deaths and injuries. We designed and tested a Vaginal Delivery Safety Checklist to improve communication and assist delivery teams' risk assessments and plans for potential complications of vaginal birth. Delivery teams found the checklist easy, convenient, and helpful. Teams completed the checklist within 2 to 3 minutes and showed improved teamwork, communication, and decision making. PMID- 26851051 TI - Gastric wall ischemia following massive gastric distension due to peptic pyloric stenosis: a case report. AB - Gastric necrosis is a rare entity mainly due to the rich collateral blood flow the stomach is supplied by. Acute gastric dilation is one of the described underlying causes, and although not fully understood, many potential alterations, such as vascular compression, herniation, volvulus, acute necrotizing gastritis, complications after abdominal surgery, anorexia, bulimia nervosa, trauma, exposure to caustic materials, diabetes, medications, infections, debilitating chronic illness, gastric outlet obstruction, aerophagia and acute pancreatitis have been described. In this report, we present a case of partial gastric ischemia with necrosis and consequent perforation of the lesser curvature of the stomach, as a result of gastric outlet obstruction due to pyloric stenosis. The patient underwent an emergency laparotomy. An atypical gastrectomy and a Heineke Mikulicz pyloroplasty were performed. We emphasize the need for the quick recognition of this condition and for the urgent management because of the high mortality rate associated with undiagnosed gastric necrosis. PMID- 26851052 TI - The face bow is irrelevant for making prostheses and planning orthognathic surgery. AB - BACKGROUND: The author addresses whether the face bow is irrelevant for all types of prosthetic work and for planning orthognathic surgery. METHODS: The author searched electronic databases to find studies whose investigators used the strongest clinical evidence (that is, randomized clinical trials) and studies whose investigators incorporated the use of cinefluorography. The author found 13 studies and 1 Internet video that provided strong evidence to support the irrelevancy of the face bow transfer. RESULTS: Evidence indicates that the face bow has nothing to do with speech, the fit and comfort of the prostheses, ridge morphology, facial contours, the color of the teeth and denture bases, the arrangement of the artificial teeth, chewing efficiency stability, and the psychological aspects of prosthodontic treatment. The cinefluorographic example showed that there was no condylar axis of rotation during functional activity, a sawing action of the mandibular incisors during the incising of toast and the mandible moving in a back and forth, rocking chair-like movement during functional activity. CONCLUSIONS: Eliminating the face bow transfer reduces the patient's chair time and the dentist's overhead expenses. The author found evidence in the results of randomized controlled trials and an online video that justify eliminating the use and teaching of the 133-year-old technique known as the face bow transfer. PRACTICAL IMPLICATIONS: Patients expect their physicians and dentists to perform only treatment procedures that are essential. The findings of this study show that the face bow transfer treatment procedure is not absolutely necessary to mount dental models on an articulator. Students', professors', schools', patients', and taxpayers' time and money can be saved by no longer teaching this 133-year-old treatment procedure. PMID- 26851053 TI - Relevance of activated hepatic stellate cells in predicting the development of pediatric liver allograft fibrosis. AB - Activated hepatic stellate cells (HSCs) are the main collagen-producing cells in liver fibrogenesis. With the purpose of analyzing their presence and relevance in predicting liver allograft fibrosis development, 162 liver biopsies of 54 pediatric liver transplantation (LT) recipients were assessed at 6 months, 3 years, and 7 years after LT. The proportion of activated HSCs, identified by alpha-smooth muscle actin (ASMA) immunostaining, and the amount of fibrosis, identified by picrosirius red (PSR%) staining, were determined by computer-based morphometric analysis. Fibrosis was also staged by using the semiquantitative liver allograft fibrosis score (LAFSc), specifically designed to score fibrosis in the pediatric LT population. Liver allograft fibrosis displayed progression over time by PSR% (P < 0.001) and by LAFSc (P < 0.001). The ASMA expression decreased in the long term, with inverse evolution with respect to fibrosis (P < 0.01). Patients with ASMA-positive HSCs area >= 8% at 6 months (n = 20) developed a higher fibrosis proportion compared to those with ASMA-positive HSCs area <= 8% (n = 34) at the same period of time and in the long term (P = 0.03 and P < 0.01, respectively), but not at 3 years (P = 0.8). ASMA expression >= 8% at 6 months was found to be an independent risk factor for 7-year fibrosis development by PSR% (r(2) = 0.5; P < 0.01) and by LAFSc (r(2) = 0.3; P = 0.03). Furthermore, ASMA expression >= 8% at 3 years showed an association with the development of fibrosis at 7 years (P = 0.02). In conclusion, there is a high proportion of activated HSCs in pediatric LT recipients. ASMA >= 8% at 6 months seems to be a risk factor for early and longterm fibrosis development. In addition, activated HSCs showed inverse evolution with respect to fibrosis in the long term. Liver Transplantation 22 822-829 2016 AASLD. PMID- 26851054 TI - Systematic reviews and meta-analyses of the accuracy of HPV tests, visual inspection with acetic acid, cytology, and colposcopy. AB - BACKGROUND: Cervical cancer screening is offered to women to identify and treat cervical intraepithelial neoplasia (CIN). OBJECTIVES: To support WHO guidelines, a systematic review was performed to compare test accuracy of the HPV test, cytology (cervical smear), and unaided visual inspection with acetic acid (VIA); and to determine test accuracy of HPV and colposcopy impression. SEARCH STRATEGY: Medline and Embase were searched up to September 2012, and experts were contacted for references. SELECTION CRITERIA: Studies of at least 100 nonpregnant women (aged >=18years) not previously diagnosed with CIN were included. DATA COLLECTION AND ANALYSIS: Two investigators independently screened and collected data. Pooled sensitivity and specificity, and absolute differences were calculated, and the quality of evidence assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). MAIN RESULTS: High to moderate quality evidence was found. The greatest difference in overtreatment occurred with VIA instead of the cervical smear (58 more per 1000 women). Differences in missed treatment ranged from 2-5 per 1000 women. For 1000 women screened positive and then sent to colposcopy, 464 would be falsely diagnosed with CIN grade 2-3 and treated. CONCLUSIONS: Although differences in sensitivity between tests could be interpreted as large, absolute differences in missed diagnoses were small. By contrast, small differences in specificity resulted in fairly large absolute differences in overtreatment. PMID- 26851055 TI - Utility of the MMPI-2-RF Validity Scales in Detection of Simulated Underreporting: Implications of Incorporating a Manipulation Check. AB - We examined the utility of the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF) underreporting Validity Scales in a simulation design with a sample of 257 undergraduate college students. Extending past research by Sellbom and Bagby, we added a manipulation check to determine whether individuals complied with instructions to underreport and examined the impact of underreporting on all of the MMPI-2-RF substantive scales. Results indicated that individuals who complied with instructions to underreport produced statistically significantly and meaningfully higher scores on the MMPI-2-RF underreporting Validity Scales (Uncommon Virtues [L-r] and Adjustment Validity [K-r]) when compared with those who received standard instructions and with individuals who did not comply with instructions to underreport. Moreover, in comparisons with both groups, participants who complied with instructions to underreport had lower scores on the majority of the substantive scales. L-r and K-r added incremental predictive utility (in reference to one another) in differentiating individuals who underreported from individuals who were given standard instructions. PMID- 26851056 TI - Control groups in studies of contrast media adverse events. PMID- 26851057 TI - Looking Under the Hood of Third-Party Punishment Reveals Design for Personal Benefit. AB - Third-party intervention, such as when a crowd stops a mugger, is common. Yet it seems irrational because it has real costs but may provide no personal benefits. In a laboratory analogue, the third-party-punishment game, third parties ("punishers") will often spend real money to anonymously punish bad behavior directed at other people. A common explanation is that third-party punishment exists to maintain a cooperative society. We tested a different explanation: Third-party punishment results from a deterrence psychology for defending personal interests. Because humans evolved in small-scale, face-to-face social worlds, the mind infers that mistreatment of a third party predicts later mistreatment of oneself. We showed that when punishers do not have information about how they personally will be treated, they infer that mistreatment of other people predicts mistreatment of themselves, and these inferences predict punishment. But when information about personal mistreatment is available, it drives punishment. This suggests that humans' punitive psychology evolved to defend personal interests. PMID- 26851058 TI - Comparing extracorporeal cardiopulmonary resuscitation with conventional cardiopulmonary resuscitation: A meta-analysis. AB - INTRODUCTION: The objective was to determine whether extracorporeal cardiopulmonary resuscitation (ECPR), when compared with conventional cardiopulmonary resuscitation (CCPR), improves outcomes in adult patients, and to determine appropriate conditions that can predict good survival outcome in ECPR patients through a meta-analysis. METHODS: We searched the relevant literature of comparative studies between ECPR and CCPR in adults, from the MEDLINE, EMBASE, and Cochrane databases. The baseline information and outcome data (survival, good neurologic outcome at discharge, at 3-6 months, and at 1 year after arrest) were extracted. Beneficial effect of ECPR on outcome was analyzed according to time interval, location of arrest (out-of-hospital cardiac arrest (OHCA) and in hospital cardiac arrest (IHCA)), and pre-defined population inclusion criteria (witnessed arrest, initial shockable rhythm, cardiac etiology of arrest and CPR duration) by using Review Manager 5.3. Cochran's Q test and I(2) were calculated. RESULTS: 10 of 1583 publications were included. Although survival to discharge did not show clear superiority in OHCA, ECPR showed statistically improved survival and good neurologic outcome as compared to CCPR, especially at 3-6 months after arrest. In the subgroup of patients with pre-defined inclusion criteria, the pooled meta-analysis found similar results in studies with pre defined criteria. CONCLUSION: Survival and good neurologic outcome tended to be superior in the ECPR group at 3-6 months after arrest. The effect of ECPR on survival to discharge in OHCA was not clearly shown. As ECPR showed better outcomes than CCPR in studies with pre-defined criteria, strict indications criteria should be considered when implementation of ECPR. PMID- 26851060 TI - A model for the implementation of cervical cancer screening and human papillomavirus vaccination in the ED: a pilot study. PMID- 26851059 TI - Design and implementation of the Resuscitation Outcomes Consortium Pragmatic Airway Resuscitation Trial (PART). AB - Airway management is an important component of resuscitation from out-of-hospital cardiac arrest (OHCA). The optimal approach to advanced airway management is unknown. The Pragmatic Airway Resuscitation Trial (PART) will compare the effectiveness of endotracheal intubation (ETI) and Laryngeal Tube (LT) insertion upon 72-h survival in adult OHCA. Encompassing United States Emergency Medical Services agencies affiliated with the Resuscitation Outcomes Consortium (ROC), PART will use a cluster-crossover randomized design. Participating subjects will include adult, non-traumatic OHCA requiring bag-valve-mask ventilation. Trial interventions will include (1) initial airway management with ETI and (2) initial airway management with LT. The primary and secondary trial outcomes are 72-h survival and return of spontaneous circulation. Additional clinical outcomes will include airway management process and adverse events. The trial will enroll a total of 3000 subjects. Results of PART may guide the selection of advanced airway management strategies in OHCA. PMID- 26851061 TI - Copeptin and high-sensitivity cardiac troponin to exclude severe coronary stenosis in patients with chest pain and coronary artery disease. AB - PURPOSE: The purpose was to evaluate the incremental value of copeptin associated with high-sensitivity cardiac T troponin (hs-cTnT) to exclude severe coronary stenosis in patients with coronary artery disease (CAD) and acute chest pain. METHODS: This monocentric prospective study included 96 consecutive patients with documented CAD and admitted to the intensive care unit for chest pain lasting for less than 10 hours. Acute coronary syndrome was excluded with electrocardiography and baseline hs-cTnT values <14 ng/L with dynamic changes <=50% 3 hours later (Roche Diagnostics, COBAS 8000). Copeptin (Thermofisher, Kryptor Compact) was considered as positive when >10 pmol/L. Primary end point was severe coronary stenosis at coronary angiography or myocardial ischemia on perfusion single photon emission computed tomography imaging. RESULTS: Mean age of patients was 60 +/- 13.8 years, and the mean time between chest pain onset and blood samples of copeptin was 4.2 +/- 2.7 hours. According to clinical decision, coronary angiography was performed in 71 patients (73.9%) and severe stenosis diagnosed in 14 of them (14.6%). No ischemia was detected on single-photon emission computed tomography imaging (n = 25). Among the 69 patients with a negative kinetic of hs cTnT and a negative baseline copeptin, 5 (7.4%) had a severe stenosis (negative predictive value, 0.93; 95% confidence interval, 0.87-0.99), 4 of them related to in-stent restenosis (negative predictive value for exclusion of native coronary stenosis, 0.98; 95% confidence interval, 0.93-1). CONCLUSIONS: For patients with preexisting CAD and acute chest pain, and once acute coronary syndrome is excluded, copeptin provides a useful additional triage strategy to exclude severe coronary stenosis, particularly those not related to in-stent restenosis. PMID- 26851062 TI - Ethical and regulatory challenges in advancing prehospital research: focus on sepsis. PMID- 26851064 TI - Paid sick leave is associated with fewer ED visits among US private sector working adults. AB - CONTEXT: The United States (US) is the only developed country that does not guarantee short-term or longer-term paid sick leave. OBJECTIVE: This study used a multiyear nationally representative database to examine the association between availability of paid sick leave and frequency of emergency department (ED) use among US private sector employees. STUDY SAMPLE: We used the National Health Interview Survey data (2012-2014). The final study sample consists of 42,460 US adults between 18 and 64years of age and working in nongovernmental private sector. RESULTS: Our results suggest that availability of paid sick leave is significantly associated with lower likelihood of ED use, for both moderate (1-3 times/year) and repeated users (4 or more times/year). After controlling for confounding factors, respondents with paid sick leave are 14% less likely to be moderate ED users (adjusted odds ratio, 0.86; 95% CI, 0.79-0.93) and 32% less likely to be repeated ED users (adjusted odds ratio, 0.68; 95% CI, 0.50-0.91). DISCUSSION: Although expansion of health insurance coverage under the Affordable Care Act has not been shown to reduce utilization of high cost health care services such as the ED, our study suggests other factors such as the availability of paid sick leave may do so, by allowing patients to seek care through other more cost-effective mechanisms (eg, primary care providers). To reduce ED utilization, health policymakers should consider alternative reforms including paid sick leave. PMID- 26851063 TI - Accuracy of bedside ultrasonography for the diagnosis of finger fractures. AB - OBJECTIVE: Diagnosis of bone fractures by ultrasonography is becoming increasingly popular in emergency medicine practice. We aimed to determine the diagnostic sensitivity and specificity of point-of-care ultrasonography (PoCUS) compared with plain radiographs in proximal and middle phalanx fractures. METHODS: Between August 2012 and July 2013, adult patients presenting to our emergency department with a possible (by clinical evaluation) proximal or middle phalanx fracture of finger were invited to participate in this prospective cohort study. From those granting consent to participate, anteroposterior and lateral radiographs were obtained. PoCUS was then performed by emergency physicians blinded to the radiograph results. The criterion standard test for diagnosis was radiograph interpretation by an orthopedic surgeon blinded to the ultrasonographic findings. RESULTS: During the study period, 212 patients with an injury to the proximal or middle phalanx presented to the emergency department. Of these, 93 patients met exclusion criteria; thus, data were analyzed from the remaining 119 patients. Fracture prevalence was 24.3%. Diagnostic sensitivity of PoCUS was 79.3% (95% confidence interval [CI], 59.7%-91.2%), specificity was 90% (95% CI, 81.4%-95.0%), positive predictive value was 71.8% (95% CI, 53.0%-85.6%), negative predictive value was 93.1% (95% CI, 85.0%-97.1%), positive likelihood ratio was 7.93 (95% CI, 4.15-15), and negative likelihood ratio was 0.23 (95% CI, 0.11-0.47). CONCLUSION: Emergency physician-performed PoCUS was moderately sensitive and specific for diagnosing proximal and middle phalanx fractures. PMID- 26851065 TI - Impaired nitric oxide production in children with MELAS syndrome and the effect of arginine and citrulline supplementation. AB - Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is one of the most frequent maternally inherited mitochondrial disorders. The pathogenesis of this syndrome is not fully understood and believed to result from several interacting mechanisms including impaired mitochondrial energy production, microvasculature angiopathy, and nitric oxide (NO) deficiency. NO deficiency in MELAS syndrome is likely to be multifactorial in origin with the decreased availability of the NO precursors, arginine and citrulline, playing a major role. In this study we used stable isotope infusion techniques to assess NO production in children with MELAS syndrome and healthy pediatric controls. We also assessed the effect of oral arginine and citrulline supplementations on NO production in children with MELAS syndrome. When compared to control subjects, children with MELAS syndrome were found to have lower NO production, arginine flux, plasma arginine, and citrulline flux. In children with MELAS syndrome, arginine supplementation resulted in increased NO production, arginine flux, and arginine concentration. Citrulline supplementation resulted in a greater increase of these parameters. Additionally, citrulline supplementation was associated with a robust increase in citrulline concentration and flux and de novo arginine synthesis rate. The greater effect of citrulline in increasing NO production is due to its greater ability to increase arginine availability particularly in the intracellular compartment in which NO synthesis takes place. This study, which is the first one to assess NO metabolism in children with mitochondrial diseases, adds more evidence to the notion that NO deficiency occurs in MELAS syndrome, suggests a better effect for citrulline because of its greater role as NO precursor, and indicates that impaired NO production occurs in children as well as adults with MELAS syndrome. Thus, the initiation of treatment with NO precursors may be beneficial earlier in life. Controlled clinical trials to assess the therapeutic effects of arginine and citrulline on clinical complications of MELAS syndrome are needed. PMID- 26851066 TI - Methamphetamine use among gay and bisexual men in Australia: Trends in recent and regular use from the Gay Community Periodic Surveys. AB - BACKGROUND: Gay and bisexual men typically report high rates of illicit drug use, including methamphetamine use. This paper aimed to analyse trends in crystal methamphetamine ('crystal') and powder methamphetamine ('speed') use among gay and bisexual men in Australia, and characterise the sociodemographic, drug use, and sexual risk practices of men who reported crystal use. METHODS: The Gay Community Periodic Surveys, routinely conducted behavioural surveillance surveys of gay men in Australia, were analysed to examine trends in recent crystal and speed use during 2005-14 (any use in the previous 6 months), and trends in regular crystal and speed use during 2007-14 (at least monthly use in the previous 6 months). Covariates of recent and regular crystal use were analysed using 2014 data. RESULTS: Speed use declined from 25.0% to 10.2% during 2005-14 (p-trend <.001), while regular speed use declined from 7.0% to 2.3% during 2007 14 (p-trend <.001). Any crystal use declined from 15.6% to 11.4% during 2005-14 (p-trend <.001) and increased during 2010-14 (from 9.6% in 2010; p-trend <.001). Regular crystal use declined from 6.1% to 4.0% during 2007-14 (p-trend <.001) and remained stable during 2010-14 (3.9% in 2010; p-trend=.64). Participants who reported regular crystal use were more likely than men who used crystal less frequently to have used gamma-hydroxybutyrate, used party drugs for sex, and to have injected drugs in the previous 6 months. High rates of crystal use and injecting were reported among HIV-positive participants. CONCLUSION: Rates of both crystal and speed use, despite fluctuations, were consistently high throughout the study period. The high rates of crystal use and associations with potentially risky sexual practices indicate that gay and bisexual men should be a particular focus for targeted harm reduction and combined harm reduction and sexual health services. PMID- 26851067 TI - Cortical thickness in bipolar disorder: a systematic review. AB - OBJECTIVES: Bipolar disorder (BD) is a debilitating illness, the psychopathology of which is associated with aberrant structural and functional differences in the brain. Despite the many advances in psychiatric research, our understanding of the complex neurobiological underpinnings of BD remains incomplete. The aim of this review was to critically examine all available published magnetic resonance imaging (MRI) research reporting cortical thickness in BD with respect to a healthy population and/or other psychiatric samples. METHODS: The systematic search encompassed all relevant studies published until November 2014. Relevant papers were identified through an online search of select databases (MEDLINE and EMBASE) using key terms bipolar disorder or mania, and cortical thickness. Two independent raters determined the eligibility of papers and performed separate data extraction to ensure quality and accuracy of reporting. RESULTS: A total of 17 papers met the criteria and were included in this review. Compared to a healthy population, the majority of studies reported decreased cortical thickness in the left anterior cingulate/paracingulate and the left superior temporal gyrus, as well as several prefrontal regions bilaterally in patients with BD. Studies also show consistency of cortical thinning in individuals with BD and schizophrenia in frontal and temporal regions, suggesting some common neuropathology. CONCLUSIONS: This systematic review further supports a link between specific structural brain abnormalities and BD. Future studies should investigate cortical thickness with respect to at-risk populations to determine whether these neuropathologies develop before or after the onset of BD. PMID- 26851068 TI - Investigations on the role of the salmon louse, Lepeophtheirus salmonis (Caligidae), as a vector in the transmission of Aeromonas salmonicida subsp. salmonicida. AB - A bacteria-parasite challenge model was used to study the role of sea lice, Lepeophtheirus salmonis (Copepoda), as a vector of Aeromonas salmonicida subsp. salmonicida. Three hypotheses were tested: (i) L. salmonis can acquire A. salmonicida subsp. salmonicida via water bath exposure; (ii) L. salmonis can acquire the bacteria via parasitizing infected Atlantic salmon, Salmo salar; and (iii) L. salmonis can transmit the bacteria to naive Atlantic salmon via parasitism. Adult L. salmonis exposed to varying A. salmonicida subsp. salmonicida suspensions (10(1) -10(7) cells mL(-1) ) for 1.0, 3.0 or 6.0 h acquired the bacteria externally (12.5-100%) and internally (10.0-100%), with higher prevalences associated with the highest concentrations and exposures. After exposure to 10(7) cells mL(-1) , viable A. salmonicida subsp. salmonicida could be isolated from the external carapace of L. salmonis for 120 h. Lepeophtheirus salmonis also acquired the bacteria externally and internally from parasitizing infected fish. Bacterial transmission was observed only when L. salmonis had acquired the pathogen internally via feeding on 'donor fish' and then by parasitizing smaller (<50 g) 'naive' fish. Under specific experimental conditions, L. salmonis can transfer A. salmonicida subsp. salmonicida via parasitism; however, its role as a mechanical or biological vector was not defined. PMID- 26851069 TI - TSPO ligand PK11195 alleviates neuroinflammation and beta-amyloid generation induced by systemic LPS administration. AB - Translocator protein 18 kDa (TSPO) is now an attractive drug target for controlling neuroinflammation. Studies applying TSPO ligands to neurodegenerative diseases, especially Alzheimer's disease (AD), were rare. Our study was aimed to evaluate the effect of PK11195, a specific TSPO ligand, in an animal model of neuroinflammation caused by systemic LPS administration. C57/BL6 mice were treated with lipopolysaccharide (LPS, 500 MUg/kg, i.p.) three days after PK11195 administration (3mg/kg, i.p.). The drugs were not discontinued until the mice were sacrificed. Cognitive function was assessed by Morris water maze (MWM) seven days after LPS injection. Chronic LPS-injection in mice was characterized by cognitive dysfunction, increased expression of cyclooxygenase (COX)-2 and TSPO, elevated Abeta content with increased expression of beta-site APP cleaving enzyme 1 (BACE-1) and insulin-degrading enzyme (IDE) as well as decreased brain progesterone and brain-derived neurophic factor (BDNF) level. PK11195 pretreatment protected cognitive function in LPS-injected animals and normalized the inflammatory proteins. Moreover, PK11195 pre-administration decreased elevated hippocampal Abetax-42 levels and increased brain levels of progesterone, allopregnanolone. However, LPS-induced BDNF decrease was not reversed by PK11195 administration. Our data demonstrated that PK11195 could protect cognitive deficits induced by chronic LPS administration. The underling mechanism may involve alleviated neuroinflammation, increased synthesis of neurosteroid and decreased Abeta accumulation accompanied by down-regulation of BACE-1. PMID- 26851070 TI - Whose "Storm and Stress" Is It? Parent and Child Reports of Personality Development in the Transition to Early Adolescence. AB - The present study investigated Big Five personality trait development in the transition to early adolescence (from the fifth to eighth grade). Personality traits were assessed in 2,761 (47% female) students over a 3-year period of time. Youths' self-reports and parent ratings were used to test for cross-informant agreement. Acquiescent responding and measurement invariance were established with latent variable modeling. Growth curve models revealed three main findings: (a) Normative mean-level changes occurred for youths' self-report data and parent ratings with modest effects in both cases. (b) Agreeableness and Openness decreased for self-reports and parent ratings, whereas data source differences were found for Conscientiousness (decreased for self-reports and remained stable for parent ratings), Extraversion (increased for self-reports and decreased for parent ratings), and Neuroticism (remained stable for self-reports and decreased for parent ratings). (c) Girls showed a more mature personality overall (self reports and parent ratings revealed higher levels of Agreeableness, Conscientiousness, and Openness) and became more extraverted in the middle of adolescence (self-reports). Personality changes modestly during early adolescence whereby change does not occur in the direction of maturation, and substantial differences exist between parent ratings and self-reports. PMID- 26851073 TI - Computation Resources for Molecular Biology: A Special Issue. PMID- 26851071 TI - Conserved Intramolecular Interactions Maintain Myosin Interacting-Heads Motifs Explaining Tarantula Muscle Super-Relaxed State Structural Basis. AB - Tarantula striated muscle is an outstanding system for understanding the molecular organization of myosin filaments. Three-dimensional reconstruction based on cryo-electron microscopy images and single-particle image processing revealed that, in a relaxed state, myosin molecules undergo intramolecular head head interactions, explaining why head activity switches off. The filament model obtained by rigidly docking a chicken smooth muscle myosin structure to the reconstruction was improved by flexibly fitting an atomic model built by mixing structures from different species to a tilt-corrected 2-nm three-dimensional map of frozen-hydrated tarantula thick filament. We used heavy and light chain sequences from tarantula myosin to build a single-species homology model of two heavy meromyosin interacting-heads motifs (IHMs). The flexibly fitted model includes previously missing loops and shows five intramolecular and five intermolecular interactions that keep the IHM in a compact off structure, forming four helical tracks of IHMs around the backbone. The residues involved in these interactions are oppositely charged, and their sequence conservation suggests that IHM is present across animal species. The new model, PDB 3JBH, explains the structural origin of the ATP turnover rates detected in relaxed tarantula muscle by ascribing the very slow rate to docked unphosphorylated heads, the slow rate to phosphorylated docked heads, and the fast rate to phosphorylated undocked heads. The conservation of intramolecular interactions across animal species and the presence of IHM in bilaterians suggest that a super-relaxed state should be maintained, as it plays a role in saving ATP in skeletal, cardiac, and smooth muscles. PMID- 26851072 TI - Structural Insights into the HWE Histidine Kinase Family: The Brucella Blue Light Activated Histidine Kinase Domain. AB - In response to light, as part of a two-component system, the Brucella blue light activated histidine kinase (LOV-HK) increases its autophosphorylation, modulating the virulence of this microorganism. The Brucella histidine kinase (HK) domain belongs to the HWE family, for which there is no structural information. The HWE family is exclusively present in proteobacteria and usually coupled to a wide diversity of light sensor domains. This work reports the crystal structure of the Brucella HK domain, which presents two different dimeric assemblies in the asymmetric unit: one similar to the already described canonical parallel homodimers (C) and the other, an antiparallel non-canonical (NC) dimer, each with distinct relative subdomain orientations and dimerization interfaces. Contrary to these crystallographic structures and unlike other HKs, in solution, the Brucella HK domain is monomeric and still active, showing an astonishing instability of the dimeric interface. Despite this instability, using cross-linking experiments, we show that the C dimer is the functionally relevant species. Mutational analysis demonstrates that the autophosphorylation activity occurs in cis. The different relative subdomain orientations observed for the NC and C states highlight the large conformational flexibility of the HK domain. Through the analysis of these alternative conformations by means of molecular dynamics simulations, we also propose a catalytic mechanism for Brucella LOV-HK. PMID- 26851074 TI - Exploiting the hypoxia sensitive non-coding genome for organ-specific physiologic reprogramming. AB - In this review we highlight the role of non-coding RNAs in the development and progression of cardiac pathology and explore the possibility of disease associated RNAs serving as targets for cardiac-directed therapeutics. Contextually, we focus on the role of stress-induced hypoxia as a driver of disease development and progression through activation of hypoxia inducible factor 1alpha (HIF1alpha) and explore mechanisms underlying HIFalpha function as an enforcer of cardiac pathology through direct transcriptional coupling with the non-coding transcriptome. In the interest of clarity, we will confine our analysis to cardiac pathology and focus on three defining features of the diseased state, namely metabolic, growth and functional reprogramming. It is the aim of this review to explore possible mechanisms through which HIF1alpha regulation of the non-coding transcriptome connects to spatiotemporal control of gene expression to drive establishment of the diseased state, and to propose strategies for the exploitation of these unique RNAs as targets for clinical therapy. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. PMID- 26851075 TI - Assembly, maintenance and dynamics of peroxisomes. AB - Peroxisomes are ubiquitous organelles of eukaryotic cells, and it is becoming increasingly clear that the biogenesis of these multi-purpose organelles is more complex than initially anticipated. Along this line, peroxisomes exhibit features, which clearly distinguish them from other cellular organelles, like their ability to import folded proteins or their capability to form de novo. However, further insight into the cellular life of peroxisomes also revealed features that they share with other organelles, such as organelle fission or regulated degradation by autophagy, that are similar for peroxisomes, mitochondria and chloroplasts. This special issue highlights recent progress in the understanding of the biogenesis of peroxisomes with emphasis on the assembly, maintenance and dynamics of the organelles. In particular, it focuses on the following areas: (i) topogenesis of peroxisomal matrix proteins as well as the structure and function of peroxisomal protein import machineries. (ii) Peroxisomal targeting of membrane proteins and de novo formation of peroxisomes. (iii) Maintenance of peroxisomes in health and disease. (iv) Proliferation and regulated degradation of peroxisomes. (v) Motility and inheritance of peroxisomes. (vi) Role of peroxisomes in the cellular context. PMID- 26851077 TI - Optimization of Ultrasound-Assisted Extraction of Cr, Cu, Zn, Cd, and Pb from Sediment, Followed by FAAS and GFAAS Analysis. AB - An ultrasound method for simultaneous extraction of Cr, Cu, Zn, Cd, and Pb from sediment, and determination by flame atomic absorption spectrometry (FAAS) and graphite furnace atomic absorption spectrometry (GFAAS) was proposed. The experimental results obtained using analytical curves and the method of standard additions agreed at a confidence level of 95% for all the analytes, as determined by FAAS and GFAAS, indicating no significant matrix effects. Recoveries ranged from 80.1 to 93.7% (certified reference material) and from 89 to 107% (spike tests). The LOD and LOQ results from the method were consistent with the techniques used (FAAS and GFAAS), with high analytical throughput. The proposed method was then used to determine Cr, Cu, Zn, Cd, and Pb in river sediment samples from Rio Doce, Minas Gerais, Brazil. The results indicated levels below those permitted by Brazilian legislation for all the analytes, with the exception of Cr. PMID- 26851076 TI - Vestiges of Ent3p/Ent5p function in the giardial epsin homolog. AB - An accurate way to characterize the functional potential of a protein is to analyze recognized protein domains encoded by the genes in a given group. The epsin N-terminal homology (ENTH) domain is an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated trafficking. In this work, we investigate the function of the single ENTH containing protein from the protist Giardia lamblia by testing its function in Saccharomyces cerevisiae. This protein, named GlENTHp (for G. lamblia ENTH protein), is involved in Giardia in endocytosis and in protein trafficking from the ER to the vacuoles, fulfilling the function of the ENTH proteins epsin and epsinR, respectively. There are two orthologs of epsin, Ent1p and Ent2p, and two orthologs of epsinR, Ent3p and Ent5p in S. cerevisiae. Although the expression of GlENTHp neither complemented growth in the ent1Deltaent2Delta mutant nor restored the GFP-Cps1 vacuolar trafficking defect in ent3Deltaent5Delta, it interfered with the normal function of Ent3/5 in the wild-type strain. The phenotype observed is linked to a defect in Cps1 localization and alpha-factor mating pheromone maturation. The finding that GlENTHp acts as dominant negative epsinR in yeast cells reinforces the phylogenetic data showing that GlENTHp belongs to the epsinR subfamily present in eukaryotes prior to their evolution into different taxa. PMID- 26851078 TI - Pharmacological Regulation of In Situ Tissue Stem Cells Differentiation for Soft Tissue Calcification Treatment. AB - Calcification of soft tissues, such as heart valves and tendons, is a common clinical problem with limited therapeutics. Tissue specific stem/progenitor cells proliferate to repopulate injured tissues. But some of them become divergent to the direction of ossification in the local pathological microenvironment, thereby representing a cellular target for pharmacological approach. We observed that HIF 2alpha (encoded by EPAS1 inclined form) signaling is markedly activated within stem/progenitor cells recruited at calcified sites of diseased human tendons and heart valves. Proinflammatory microenvironment, rather than hypoxia, is correlated with HIF-2alpha activation and promoted osteochondrogenic differentiation of tendon stem/progenitor cells (TSPCs). Abnormal upregulation of HIF-2alpha served as a key switch to direct TSPCs differentiation into osteochondral-lineage rather than teno-lineage. Notably, Scleraxis (Scx), an essential tendon specific transcription factor, was suppressed on constitutive activation of HIF-2alpha and mediated the effect of HIF-2alpha on TSPCs fate decision. Moreover, pharmacological inhibition of HIF-2alpha with digoxin, which is a widely utilized drug, can efficiently inhibit calcification and enhance tenogenesis in vitro and in the Achilles's tendinopathy model. Taken together, these findings reveal the significant role of the tissue stem/progenitor cells fate decision and suggest that pharmacological regulation of HIF-2alpha function is a promising approach for soft tissue calcification treatment. PMID- 26851079 TI - Nanocomposites of gold nanoparticles and graphene oxide towards an stable label free electrochemical immunosensor for detection of cardiac marker troponin-I. AB - A stable label-free amperometric immunosensor is presented based on gold nanoparticles and graphene oxide nanocomposites for detection of cardiac troponin I in the early diagnosis of myocardial infarction. For designing of the sensing platform, firstly the nanocomposites based on GO and AuNPs were prepared and anchored on electrode surfaces. The formed nanocomposites provided a platform with big surface area for loading anti-cTnI capture antibody, and worked as a bridge for fast electron transfer subsequently increased the sensitivity. Moreover, the linkages between AuNP, GO, and electrodes were based on covalent bonding by aryldiazonium salt coupling chemistry, which favors the stability of the sensing interface. Finally, the anti-cTnI detection antibody was immobilized on GO tailored with ferrocene molecules, functioning as the signal reporter for the detection of cTnI. The modification process was monitored using electrochemistry, SEM, XPS. The herein immunosensor demonstrates a good selectivity and high sensitivity against human-cTnI, and is capable of detecting cTnI at concentrations as low as 0.05 ng mL(-1), which is 100 times lower than that possible by conventional methods. It is potential to design the portable sensing platform based on AuNPs and GO nanocomposites for future point-of-care diagnostics. PMID- 26851080 TI - Chromatographic fingerprinting: An innovative approach for food 'identitation' and food authentication - A tutorial. AB - Fingerprinting methods describe a variety of analytical methods that provide analytical signals related to the composition of foodstuffs in a non-selective way such as by collecting a spectrum or a chromatogram. Mathematical processing of the information in such fingerprints may allow the characterisation and/or authentication of foodstuffs. In this context, the particular meaning of 'fingerprinting', in conjunction with 'profiling', is different from the original meanings used in metabolomics. This fact has produced some confusion with the use of these terms in analytical papers. Researchers coming from the metabolomic field could use 'profiling' or 'fingerprinting' on a different way to researchers who are devoted to food science. The arrival of an eclectic discipline, named 'foodomics' has not been enough to allay this terminological problem, since the authors keep on using the terms with both meanings. Thus, a first goal of this tutorial is to clarify the difference between both terms. In addition, the chemical approaches for food authentication, i.e., chemical markers, component profiling and instrumental fingerprinting, have been described. A new term, designated as 'food identitation', has been introduced in order to complete the life cycle of the chemical-based food authentication process. Chromatographic fingerprinting has been explained in detail and some strategies which could be applied has been clarified and discussed. Particularly, the strategies for chromatographic signals acquisition and chromatographic data handling are unified in a single framework. Finally, an overview about the applications of chromatographic (GC and LC) fingerprints in food authentication using different chemometric techniques has been included. PMID- 26851081 TI - Standard dilution analysis of beverages by microwave-induced plasma optical emission spectrometry. AB - In this work, standard dilution analysis (SDA) is combined with microwave-induced plasma optical emission spectrometry (MIP OES) to determine seven elements in coffee, green tea, energy drink, beer, whiskey and cachaca (Brazilian hard liquor). No sample preparation other than simple dilution in HNO3 1% v v(-1) is required. Due to relatively low plasma temperatures, matrix effects may compromise accuracies in MIP OES analyzes of complex samples. The method of standard additions (SA) offers enhanced accuracies, but is time-consuming and labor intensive. SDA offers a simpler, faster approach, with improved accuracies for complex matrices. In this work, SDA's efficiency is evaluated by spike experiments, and the results are compared to the traditional methods of external calibration (EC), internal standard (IS), and standard additions (SA). SDA is comparable to the traditional calibration methods, and it provides superior accuracies for applications involving ethanol-containing beverage samples. The SDA-MIP OES procedure is effective. Using only two calibration solutions, it may be easily automated for accurate and high sample throughput routine applications. PMID- 26851082 TI - A local pre-processing method for near-infrared spectra, combined with spectral segmentation and standard normal variate transformation. AB - Pre-processing of near-infrared (NIR) spectral data has become a necessary part of chemometrics modeling and is widely used in many practical applications. The objective of the pre-processing is to remove physical phenomena in the spectra in order to improve subsequent qualitative or quantitative analysis. Herein, a localized version of standard normal variate (SNV) is proposed, in which the correction parameters are estimated from local spectral areas. The method of determining the optimal spectral segmentation is also presented. Compared with full range methods, the local method demonstrates advantages in spectral linearity correction, model interpretation and prediction accuracy. Several benchmark NIR data sets were studied in our experiments; the proposed method achieved comparable performance against proven full range methods, with the reduction of prediction errors being statistically significant in many cases. PMID- 26851084 TI - Covalent functionalization of single-walled carbon nanotubes with polytyrosine: Characterization and analytical applications for the sensitive quantification of polyphenols. AB - This work reports the synthesis and characterization of single-walled carbon nanotubes (SWCNT) covalently functionalized with polytyrosine (Polytyr); the critical analysis of the experimental conditions to obtain the efficient dispersion of the modified carbon nanotubes; and the analytical performance of glassy carbon electrodes (GCE) modified with the dispersion (GCE/SWCNT-Polytyr) for the highly sensitive quantification of polyphenols. Under the optimal conditions, the calibration plot for the amperometric response of gallic acid (GA) shows a linear range between 5.0 * 10(-7) and 1.7 * 10(-4) M, with a sensitivity of (518 +/- 5) m AM(-1) cm(-2), and a detection limit of 8.8 nM. The proposed sensor was successfully used for the determination of total polyphenolic content in tea extracts. PMID- 26851083 TI - Improved prediction of drug-target interactions using regularized least squares integrating with kernel fusion technique. AB - Identification of drug-target interactions (DTI) is a central task in drug discovery processes. In this work, a simple but effective regularized least squares integrating with nonlinear kernel fusion (RLS-KF) algorithm is proposed to perform DTI predictions. Using benchmark DTI datasets, our proposed algorithm achieves the state-of-the-art results with area under precision-recall curve (AUPR) of 0.915, 0.925, 0.853 and 0.909 for enzymes, ion channels (IC), G protein coupled receptors (GPCR) and nuclear receptors (NR) based on 10 fold cross validation. The performance can further be improved by using a recalculated kernel matrix, especially for the small set of nuclear receptors with AUPR of 0.945. Importantly, most of the top ranked interaction predictions can be validated by experimental data reported in the literature, bioassay results in the PubChem BioAssay database, as well as other previous studies. Our analysis suggests that the proposed RLS-KF is helpful for studying DTI, drug repositioning as well as polypharmacology, and may help to accelerate drug discovery by identifying novel drug targets. PMID- 26851085 TI - Poly(amino acid)-based thermoresponsive molecularly imprinted magnetic nanoparticles for specific recognition and release of lysozyme. AB - In this study, poly(amino acid)-based thermoresponsive molecularly imprinted magnetic nanoparticles for recognition and release of lysozyme was prepared via surface imprinting method. For constructing the molecularly imprinted polymer (MIP) layer, amino acid-based thermoresponsive monomer (N-methacryloyl-L-alanine methyl ester, MA-L-Ala-OMe) was mainly selected for the functional monomer along with N,N'-methylenebis(acrylamide) as the crosslinker. The resultant magnetic MIP nanoparticles were characterized in detail. Meanwhile, the dynamic light scattering studies and swelling ratios measurements were carried out for demonstrating the thermoresponsive property of the imprinted nanoparticles. The prepared magnetic MIP nanoparticles showed good adsorption capacity and selective recognition properties to lysozyme. Moreover, the fast adsorption process could reach equilibrium within 15 min. Importantly, the capture and release of lysozyme could be easily realized simply by altering the temperature of aqueous solution. Furthermore, the prepared imprinted nanoparticles were applied to separate lysozyme from the real egg white samples. The results proved that the thermoresponsive MIPs based on MA-L-Ala-OMe have great potential for selectively enriching target proteins in real samples. PMID- 26851086 TI - Phosphopeptide enrichment: Development of magnetic solid phase extraction method based on polydopamine coating and Ti(4+)-IMAC. AB - Protein post translational modifications currently represent one of the main challenges with proteomic analysis, due to the important biological role they play within cells. Protein phosphorylation is one of the most important, with several approaches developed for phosphopeptides enrichment and analysis, essential for comprehensive phosphoproteomic analysis. However, the development of new materials for phosphopeptides enrichment may overcome previous drawbacks and improve enrichment of such peptides. In this regard, new magnetic stationary phases based on polydopamine coating and Ti(4+) immobilization exploit the potential of IMAC enrichment and couple it with the versatility of magnetic solid phase extraction. In this work the use of such stationary phase was extended from the MALDI proof of concept stage with the development of an optimized method for phosphopeptides enrichment compatible with typical shotgun proteomics experimental workflows. Different loading and elution buffers were tested to improve phosphopeptides recovery and enrichment selectivity. Finally, the analysis of isolated peptides pointed out that polydopamine alone is an ideal support matrix for polar post translational modifications because it enables to reduce unspecific binding and preferentially binds hydrophilic peptides. PMID- 26851087 TI - Simultaneous high-throughput determination of interaction kinetics for drugs and cyclodextrins by high performance affinity chromatography with mass spectrometry detection. AB - The individual determination of the apparent dissociation rate constant (kd,app) using high performance affinity chromatography (HPAC) is a tedious process requiring numerous separate tests and massive data fitting, unable to provide the apparent association rate constant (ka) and equilibrium binding constant (Ka). In this study, a HPAC with mass spectrometry detection (HPAC-MS/MS) was employed to determine the drug-cyclodextrin (CD) interaction kinetics with low sample loading quantity (<10 ng per injection for single compound) and high-throughput yield as twenty drugs determined in one injection. The kd,app measured by HPAC-MS/MS approach were 0.89 +/- 0.07, 4.34 +/- 0.01, 1.48 +/- 0.01 and 7.77 +/- 0.04 s(-1) for ketoprofen, trimethoprim, indapamide and acetaminophen, with kd,app for acetaminophen consistent with that from the HPAC method with UV detector in our previous studies. For twenty drugs with diverse structures and chemical properties, good correlationship was found between kd,app measured by single compound analysis method and high-throughput HPAC-MS/MS approach, with the correlation coefficient of 0.987 and the significance F less than 0.001. Comprehensive quantification of ka,app, kd,app and Ka values was further performed based on the measurement of kd,app by peak profiling method and Ka by the peak fitting method. And the investigation of the drug-CD interaction kinetics under different conditions indicated that the column temperature and mobile phase composition significantly affected the determination of ka,app, kd,app and Ka while also dependent on the acidity and basicity of drugs. In summary, the high-throughput HPAC-MS/MS approach has been demonstrated high efficiency in determination of the drug-CD primary interaction kinetic parameter, especially, kd,app, being proven as a novel tool in screening the right CD for the solubilization of the right drug. PMID- 26851088 TI - Towards metals analysis using corona discharge ionization ion mobility spectrometry. AB - For the first time, the capability of corona discharge ionization ion mobility spectrometry (CD-IMS) in the determination of metal complex was evaluated. The extreme simplicity of dispersive liquid-liquid microextraction (DLLME) coupled to the high sensitivity of CD-IMS measurement could make this combination really useful for simple, rapid, and sensitive determination of metals in different samples. In this regard, mercury, as a model metal, was complexed with diethyldithiocarbamate (DEDTC), and then extracted into the carbon tetrachloride using DLLME. Some parameters affecting the extraction efficiency, including the type and volume of the extraction solvent, the type and volume of the disperser solvent, the concentration of the chelating agent, salt addition and, pH were exhaustively investigated. Under the optimized condition, the enrichment factor was obtained to be 142. The linear range of 0.035-10.0 MUg mL(-1) with r(2) = 0.997 and the detection limit of 0.010 MUg mL(-1) were obtained. The relative standard deviation values were calculated to be lower than 4% and 8% for intra day and inter-day, respectively. Finally, the developed method was successfully applied for the extraction and determination of mercury in various real samples. The satisfactory results revealed the capability of the proposed method in trace analysis without tedious derivatization or hydride generation. PMID- 26851089 TI - New look inside human breast ducts with Raman imaging. Raman candidates as diagnostic markers for breast cancer prognosis: Mammaglobin, palmitic acid and sphingomyelin. AB - Looking inside the human body fascinated mankind for thousands of years. Current diagnostic and therapy methods are often limited by inadequate sensitivity, specificity and spatial resolution. Raman imaging may bring revolution in monitoring of disease and treatment. The main advantage of Raman imaging is that it gives spatial information about various chemical constituents in defined cellular organelles in contrast to conventional methods (liquid chromatography/mass spectrometry, NMR, HPLC) that rely on bulk or fractionated analyses of extracted components. We demonstrated how Raman imaging can drive the progress on breast cancer just unimaginable a few years ago. We looked inside human breast ducts answering fundamental questions about location and distribution of various biochemical components inside the lumen, epithelial cells of the duct and the stroma around the duct during cancer development. We have identified Raman candidates as diagnostic markers for breast cancer prognosis: carotenoids, mammaglobin, palmitic acid and sphingomyelin as key molecular targets in ductal breast cancer in situ, and propose the molecular mechanisms linking oncogenes with lipid programming. PMID- 26851090 TI - Colorimetric detection of hepatitis B virus (HBV) DNA based on DNA-templated copper nanoclusters. AB - DNA detection plays an important role in early diagnosis of genetic disease. The conventional detection methods of DNA are based on expensive equipment, which do not meet the demands of developing countries. Thus, we developed a colorimetric method, which could be observed with naked eye and used copper nanoclusters for cost-effective. Moreover, the target of this method is the DNA in Hepatitis B virus that is one of the most popular chronic viral infections in developing countries over the past years. Our method was sensitive and the limit of detection was 12 * 10(9) molecules. Three-base-pair mismatches target DNA was detected easily. These results revealed the favorable sensitivity and selectivity of this approach. Most importantly, our method may have potential applications in correct diagnosis of genetic disease and monitoring of gene therapy in the poverty-stricken areas. PMID- 26851091 TI - Molecular structure and thermodynamic predictions to create highly sensitive microRNA biosensors. AB - Many studies have established microRNAs (miRNAs) as post-transcriptional regulators in a variety of intracellular molecular processes. Abnormal changes in miRNA have been associated with several diseases. However, these changes are sometimes subtle and occur at nanomolar levels or lower. Several biosensing hurdles for in situ cellular/tissue analysis of miRNA limit detection of small amounts of miRNA. Of these limitations the most challenging are selectivity and sensor degradation creating high background signals and false signals. Recently we developed a reporter+probe biosensor for let-7a that showed potential to mitigate false signal from sensor degradation. Here we designed reporter+probe biosensors for miR-26a-2-3p and miR-27a-5p to better understand the effect of thermodynamics and molecular structures of the biosensor constituents on the analytical performance. Signal changes from interactions between Cy3 and Cy5 on the reporters were used to understand structural aspects of the reporter designs. Theoretical thermodynamic values, single stranded conformations, hetero- and homodimerization structures, and equilibrium concentrations of the reporters and probes were used to interpret the experimental observations. Studies of the sensitivity and selectivity revealed 5-9 nM detection limits in the presence and absence of interfering off-analyte miRNAs. These studies will aid in determining how to rationally design reporter+probe biosensors to overcome hurdles associated with highly sensitive miRNA biosensing. PMID- 26851092 TI - Novel CeO2-CuO-decorated enzymatic lactate biosensors operating in low oxygen environments. AB - The detection of the lactate level in blood plays a key role in diagnosis of some pathological conditions including cardiogenic or endotoxic shocks, respiratory failure, liver disease, systemic disorders, renal failure, and tissue hypoxia. Here, we described for the first time the use of a novel mixed metal oxide solution system to address the oxygen dependence challenge of first generation amperometric lactate biosensors. The biosensors were constructed using ceria copper oxide (CeO2-CuO) mixed metal oxide nanoparticles for lactate oxidase immobilization and as electrode material. The oxygen storage capacity (OSC, 492 MUmol-O2/g) of these metal oxides has the potential to reduce the oxygen dependency, and thus eliminate false results originated from the fluctuations in the oxygen concentration. In an effort to compare the performance of our novel sensor design, ceria nanoparticle decorated lactate sensors were also constructed. The enzymatic activity of the sensors were tested in oxygen-rich and oxygen-lean solutions. Our results showed that the OSC of the electrode material has a big influence on the activity of the biosensors in oxygen-lean environments. While the CeO2 containing biosensor showed an almost 21% decrease in the sensitivity in a O2-depleted solution, the CeO2-CuO containing electrode, with a higher OSC value, experienced no drop in sensitivity when moving from oxygen-rich to oxygen-lean conditions. The CeO2-CuO decorated sensor showed a high sensitivity (89.3 +/- 4 MUA mM(-1) cm(-2)), a wide linear range up to 0.6 mM, and a low limit of detection of 3.3 MUM. The analytical response of the CeO2 CuO decorated sensors was studied by detecting lactate in human serum with good selectivity and reliability. The results revealed that CeO2-CuO containing sensors are promising candidates for continuous lactate detection. PMID- 26851093 TI - Simple, quantitative method for low molecular weight dissolved organic matter extracted from natural waters based upon high performance counter-current chromatography. AB - A simple, high-performance counter-current chromatography method with sequential UV absorbance (254 nm) and evaporative light scattering detection (ELSD) was developed for the quantification of pre-extracted low molecular weight dissolved organic matter (DOM) extracted from natural waters. The method requires solid phase extraction (SPE) extraction of only small volumes of water samples, here using poly(styrenedivinylbenzene)-based extraction cartridges (Varian PPL). The extracted and concentrated DOM was quantified using reversed-phase high performance counter-current chromatography (HPCCC), with a water/methanol (5:5) mobile phase and hexane/ethyl acetate (3:7) stationary phase. The critical chromatographic parameters were optimised, applying a revolution speed of 1900 rpm and a flow-rate of 1 mL min(-1). Under these conditions, 50 MUL of extracted DOM solution could be injected and quantified using calibration against a reference natural dissolved material (Suwannee River), based upon UV absorbance at 254 nm and ELSD detection. Both detection methods provided excellent linearity (R(2) > 0.995) for DOM across the concentration ranges of interest, with limits of detection of 4 MUg ml(-1) and 7 MUg ml(-1) for ELSD and UV absorbance, respectively. The method was validated for peak area precision (<5%), and accuracy and recovery based upon spiking seawater samples prior to extraction, together with DOM solutions post-extraction (>95% recovery). The developed method was applied to the determination of the concentration of DOM in seawater, based upon initial sample volumes as small as 20 mL. PMID- 26851094 TI - BVA and BSAVA call for a ban on electric pulse collars. PMID- 26851095 TI - Brucellosis: pre-export testing requirement ends in Northern Ireland. PMID- 26851096 TI - Case dismissed against south London veterinary surgeon. PMID- 26851097 TI - Vet struck off following convictions. PMID- 26851098 TI - Wales to penalise cattle keepers who flout TB rules. PMID- 26851099 TI - Renewal of TB testing contracts. PMID- 26851100 TI - Veterinary medicines update. AB - The following information has been produced for Veterinary Record by the Veterinary Medicines Directorate (VMD) to provide an update for veterinary surgeons on recent changes to marketing authorisations for veterinary medicines in the UK and on other relevant issues. PMID- 26851101 TI - Cases of parasitic pneumonia in Scottish cattle. AB - Parasitic pneumonia in cattleNutritional osteodystrophy in cattleWhite liver disease in lambsErysipelas in pigsLead poisoning and atherosclerosis in an eagle These are among matters discussed in the disease surveillance report for October 2015 from SAC Consulting: Veterinary Services (SAC C VS). PMID- 26851102 TI - Enhancing collaboration in the UK animal welfare research community. PMID- 26851103 TI - Diagnosis of feline mycobacteriosis: Feline mycobacteriosis. PMID- 26851104 TI - Public good, private good, or both? PMID- 26851105 TI - Expert generalists. PMID- 26851106 TI - Study on epilepsy in the Italian spinone. PMID- 26851107 TI - Use of antibiotics in animals and people. PMID- 26851115 TI - Masterclass in veterinary public health. AB - Each summer, one student from each vet school in the British Isles gets the chance to attend a week-long masterclass to learn more about veterinary public health. Last year, Hannah Clifford was one of them. Here she explains how her understanding of the relevance and responsibility of vets working in public health has changed. PMID- 26851116 TI - Ten-minute chat. AB - Richard Chamings stood as a parliamentary candidate for the UK Independence Party in the general election last May. Born in Devon, he graduated from Edinburgh, and is a companion animal vet at White House Vets in Malvern, which he established in 1985. PMID- 26851117 TI - Treatment of anxiety and depression: medicinal plants in retrospect. AB - Anxiety and depression are complex heterogeneous psychiatric disorders and leading causes of disability worldwide. This review summarizes reports on the fundamentals, prevalence, diagnosis, neurobiology, advancement in treatment of these diseases and preclinical assessment of botanicals. This review was conducted through bibliographic investigation of scientific journals, books, electronic sources, unpublished theses and electronic medium such as ScienceDirect and PubMed. A number of the first-line drugs (benzodiazepine, azapirone, antidepressant tricyclics, monoamine oxidase inhibitors, serotonin selective reuptake inhibitors, noradrenaline reuptake inhibitors, serotonin and noradrenaline reuptake inhibitors, etc.) for the treatment of these psychiatric disorders are products of serendipitous discoveries. Inspite of the numerous classes of drugs that are available for the treatment of anxiety and depression, full remission has remained elusive. The emerging clinical cases have shown increasing interests among health practitioners and patients in phytomedicine. The development of anxiolytic and antidepressant drugs of plant origin takes advantage of multidisciplinary approach including but not limited to ethnopharmacological survey (careful investigation of folkloric application of medicinal plant), phytochemical and pharmacological studies. The selection of a suitable plant for a pharmacological study is a basic and very important step. Relevant clues to achieving this step include traditional use, chemical composition, toxicity, randomized selection or a combination of several criteria. Medicinal plants have been and continue to be a rich source of biomolecule with therapeutic values for the treatment of anxiety and depression. PMID- 26851118 TI - Triage tests should not be used to challenge the sensitivity of a full clinical examination for detecting dehydration. PMID- 26851120 TI - The effect of diabetes knowledge and attitudes on self-management and quality of life among people with type 2 diabetes. AB - We examined the effect of diabetes knowledge and attitudes on self-management and quality of life (QoL) of people with type 2 diabetes mellitus (T2DM). We employed a cross-sectional study design. A total of 137 female and 129 male participants with T2DM completed the diabetes knowledge scale (DKN), Diabetes Integration Scale-19 (ATT19), Summary of Diabetes Self-care Activities (SDSCA) scale, and Diabetes Quality of Life (DQoL) scale, measuring diabetes knowledge, attitudes, self-management, and QoL respectively. The SDSCA scale measures diet, exercise, blood glucose monitoring, and foot care. The DQoL scale measures satisfaction and impact of QoL. An initial path model that tested the inter-relationships of the study variables was first identified based on previous research. Then, the path model was tested using Mplus 7.3. In the final model, diabetes knowledge was a significant predictor of attitudes and self-management in terms of blood glucose monitoring and foot care. Attitudes was a significant predictor of impact of QoL. Self-management in terms of blood glucose monitoring was a significant predictor of impact of QoL and diet was a significant predictor of satisfaction and impact of QoL. Exercise and foot care aspects of Self-management were significant predictors of satisfaction and impact of QoL respectively. The final model showed a good fit to the data: RMSEA = .045 (90% CI: .009, .071; Clfit = .601), CFI = .950, SRMR = .058. The findings suggest a theoretical basis to direct the development of appropriate health programs and interventions for improving QoL in people with T2DM and warrant replication in diverse samples. PMID- 26851119 TI - Serum Interleukin-6 Levels and Pulmonary Function in Ataxia-Telangiectasia. AB - OBJECTIVE: To evaluate the potential link between systemic inflammation and impaired lung function in people with ataxia-telangiectasia (A-T), we hypothesized that serum levels of interleukin (IL)-6, a proinflammatory cytokine, would correlate inversely with lung function in subjects with A-T. STUDY DESIGN: Consecutive subjects with A-T were recruited from the Johns Hopkins Outpatient A T Clinical Center. Serum levels of IL-6 and 8 were measured by enzyme-linked immunosorbent assay. Spirometry was performed in subjects >= 6 years of age on the same day that serum was obtained for measurements of cytokines. RESULTS: Approximately 80% of subjects had elevated serum IL-6 levels (> 1.0 pg/mL). No association was found between elevated IL-6 and age. Elevated IL-8 levels were found in 23.6% of subjects, and all subjects with elevated IL-8 levels had elevated IL-6 levels. Subjects with elevated IL-6 levels (mean: 6.14 +/- 7.47 pg/mL) had significantly lower mean percent forced vital capacity (FVC%, 50.5% +/ 17.8%) compared with subjects with normal serum IL-6 levels (FVC% of 66.2 +/- 16.1, P = .018). Greater IL-6 levels were associated with lower FVC% even after adjustment for receiving gamma globulin therapy (P = .024) and supplemental nutrition (P = .055). CONCLUSIONS: An association was found between elevated serum IL-6 levels and lower lung function in subjects with A-T. In addition, subjects with both elevated IL-6 and IL-8 had the lowest mean lung function. These findings indicate that markers for systemic inflammation may be useful in identifying individuals with A-T at increased risk for lower lung function and may help in assessing response to therapy. PMID- 26851121 TI - Evaluating HPV-negative CIN2+ in the ATHENA trial. AB - A post hoc analysis of the ATHENA study was performed to determine whether true HPV-negative cervical lesions occur and whether they have clinical relevance. The ATHENA database was searched for all CIN2 or worse (CIN2+) cases with cobas HPV negative results and comparison was made with Linear Array (LA) and Amplicor to detect true false-negative HPV results. Immunostaining with p16 was performed on these cases to identify false-positive histology results. H&E slides were re reviewed by the study pathologists with knowledge of patient age, HPV test results and p16 immunostaining. Those with positive p16 immunostaining and/or a positive histopathology review underwent whole tissue section HPV PCR by the SPF10/LiPA/RHA system. Among 46,887 eligible women, 497 cases of CIN2+ were detected, 55 of which tested negative by the cobas((r)) HPV Test (32 CIN2, 23 CIN3/ACIS). By LA and/or Amplicor, 32 CIN2+ (20 CIN2, 12 CIN3/ACIS) were HPV positive and categorized as false-negatives by cobas HPV; nine of 12 false negative CIN3/ACIS cases were p16+. There were 23 cases (12 CIN2, 11 CIN3/ACIS) negative by all HPV tests; seven of 11 CIN3/ACIS cases were p16+. H&E slides were available for six cases for re-review and all were confirmed as CIN3/ACIS. Tissue PCR was performed on the six confirmed CIN3/ACIS cases (and one without confirmation): four were positive for HPV types not considered oncogenic, two were positive for oncogenic genotypes and one was indeterminate. In summary, subanalysis of a large cervical cancer screening study did not identify any true CIN3/ACIS not attributable to HPV. PMID- 26851122 TI - Successful induction of sclerostin in human-derived fibroblasts by 4 transcription factors and its regulation by parathyroid hormone, hypoxia, and prostaglandin E2. AB - Sclerostin, coded by SOST, is a secretory protein that is specifically expressed in osteocytes and suppresses osteogenesis by inhibiting WNT signaling. The regulatory mechanism underlying SOST expression remains unclear mainly due to the absence of an adequate human cell model. Thus, we herein attempted to establish a cell model of human dermal fibroblasts in order to investigate the functions of sclerostin. We selected 20 candidate transcription factors (TFs) that induce SOST expression by analyzing gene expression patterns in the human sarcoma cell line, SaOS-2, between differentiation and maintenance cultures using microarrays. An effective set of TFs to induce SOST expression was sought by their viral transduction into fibroblasts, and a combination of four TFs: ATF3, KLF4, PAX4, and SP7, was identified as the most effective inducer of SOST expression. Quantitative PCR demonstrated that the expression levels of SOST in fibroblasts treated with the 4 TFs were 199- and 1439-fold higher than those of the control after 1-week and 4-week cultures, respectively. The level of sclerostin in the conditioned medium, as determined by ELISA, was 21.2pmol/l 4weeks after the transduction of the 4 TFs. Interestingly, the production of Dickkopf1 (DKK1), another secreted inhibitor of WNT signaling, was also increased by transduction of these 4 TFs. Parathyroid hormone (PTH) significantly suppressed the induced SOST by 38% and sclerostin by 82% that of the vehicle. Hypoxia increased the induced SOST by 62% that of normoxia. Furthermore, prostaglandin E2 (PGE2) increased SOST expression levels to 16-fold those of the vehicle. In conclusion, the efficient induction of SOST expression and sclerostin production was achieved in human dermal fibroblasts by the transduction of ATF3, KLF4, PAX4, and SP7, and the induced SOST and sclerostin were regulated by PTH, hypoxia, and PGE2. This model may contribute to elucidating the regulatory mechanisms underlying SOST expression and advancing drug development for metabolic bone diseases. PMID- 26851123 TI - Prostaglandin-mediated inhibition of PTH-stimulated beta-catenin signaling in osteoblasts by bone marrow macrophages. AB - Bone marrow macrophages (BMMs), in the presence of cyclooxygenase-2 (Cox2) produced PGE2, secrete an inhibitory factor in response to Rankl that blocks PTH stimulated osteoblastic differentiation. This study was to determine if the inhibitory factor also blocks PTH-stimulated Wnt signaling. Primary calvarial osteoblasts (POBs) were co-cultured with conditioned medium (CM) from Rankl treated wild type (WT) BMMs, which make the inhibitory factor, and Cox2 knockout (KO) BMMs, which do not. PTH induced cAMP production was blocked by WT CM but not by KO CM. In the presence of KO CM, PTH induced phosphorylation at beta-catenin serine sites, ser552 and ser675, previously shown to be phosphorylated by protein kinase A (PKA). Phosphorylation was blocked by WT CM and by H89, a PKA inhibitor. PTH did not increase total beta-catenin. PTH-stimulated transcription factor/lymphoid enhancer-binding factor response element activity in POBs was blocked by WT CM and by serum amyloid A (SAA), the human recombinant analog of murine Saa3, which has recently been shown to be the inhibitory factor. In POBs cultured with Cox2 KO CM, PTH increased expression of multiple genes associated with the anabolic actions of PTH and decreased expression of Wnt antagonists. This differential regulation of gene expression was not seen in POBs cultured with WT CM. These data highlight the ability of PTH to phosphorylate beta-catenin directly via PKA and demonstrate the ability of a Cox2-dependent inhibitory factor, secreted by Rankl-stimulated BMMs, to abrogate PTH stimulated beta catenin signaling. Our results suggest that PTH can stimulate a novel negative feedback of its anabolic actions by stimulating Rankl and Cox2 expression. PMID- 26851124 TI - Elcatonin prevents bone loss caused by skeletal unloading by inhibiting preosteoclast fusion through the unloading-induced high expression of calcitonin receptors in bone marrow cells. AB - This study aimed to clarify whether elcatonin (EL) has a preventive action on bone dynamics in skeletal unloading. Seven-week-old male C57BL/6J mice with either ground control (GC) or tail suspension (TS) were administered EL 20U/kg or a vehicle (veh) three times per week and assigned to one of the following four groups: GCEL, GCveh, TSEL, and TSveh. Blood samples and bilateral femurs and tibias of the mice were obtained for analysis. After 7days of unloading, the trabecular bone mineral density in the distal femur obtained via peripheral quantitative computed tomography and the trabecular bone volume were significantly higher in the TSEL group than in the TSveh group. The bone resorption histomorphometric parameters, such as the osteoclast surface and osteoclast number, were significantly suppressed in the TSEL mice, whereas the number of preosteoclasts was significantly increased. The plasma level of tartrate-resistant acid phosphatase-5b (TRACP-5b) was significantly lower in the TSEL group than in all other groups. In the bone marrow cell culture, the number of TRACP-positive (TRACP(+)) multinucleated cells was significantly lower in the TSEL mice than in the TSveh mice, whereas the number of TRACP(+) mononucleated cells was higher in the TSEL mice. On day 4, the expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), cathepsin K and d2 isoform of vacuolar ATPase V0 domain (ATP6V0D2) mRNA in the bone marrow cells in the TSEL mice was suppressed, and the expression of calcitonin receptor (Calcr) mRNA on day 1 and Calcr antigen on day 4 were significantly higher in the TSveh mice than in the GCveh mice. EL prevented the unloading-induced bone loss associated with the high expression of Calcr in the bone marrow cells of mouse hindlimbs after tail suspension, and it suppressed osteoclast development from preosteoclasts to mature osteoclasts through bone-resorbing activity. This study of EL-treated unloaded mice provides the first in vivo evidence of a physiological role of EL in the inhibition of the differentiation process from preosteoclasts to osteoclasts. PMID- 26851125 TI - Computational Study and Modified Design of Selective Dopamine D3 Receptor Agonists. AB - Dopamine D3 receptor (D3 R) is considered as a potential target for the treatment of nervous system disorders, such as Parkinson's disease. Current research interests primarily focus on the discovery and design of potent D3 agonists. In this work, we selected 40 D3 R agonists as the research system. Comparative molecular field analysis (CoMFA) of three-dimensional quantitative structure activity relationship (3D-QSAR), structure-selectivity relationship (3D-QSSR), and molecular docking was performed on D3 receptor agonists to obtain the details at atomic level. The results indicated that both the CoMFA model (r(2) = 0.982, q(2) = 0.503, rpred2 = 0.893, SEE = 0.057, F = 166.308) for structure-activity and (r(2) = 0.876, q(2) = 0.436, rpred2 = 0.828, F = 52.645) for structure selectivity have good predictive capabilities. Furthermore, docking studies on three compounds binding to D3 receptor were performed to analyze the binding modes and interactions. The results elucidate that agonists formed hydrogen bond and hydrophobic interactions with key residues. Finally, we designed six molecules under the guidance of 3D-QSAR/QSSR models. The activity and selectivity of designed molecules have been improved, and ADMET properties demonstrate they have low probability of hepatotoxicity (<0.5). These results from 3D-QSAR/QSSR and docking studies have great significance for designing novel dopamine D3 selective agonists in the future. PMID- 26851126 TI - Interventions for preventing delirium in older people in institutional long-term care. PMID- 26851127 TI - Morcellator's Port-site Metastasis of a Uterine Smooth Muscle Tumor of Uncertain Malignant Potential After Minimally Invasive Myomectomy. AB - Since the safety warning from the US Food and Drug Administration on the use of power morcellators, minimally invasive procedures involving the removal of uterine myomas and large uteri are under scrutiny. Growing evidence suggests that morcellation of undiagnosed uterine malignancies is associated with worse survival outcomes of patients affected by uterine sarcoma. However, to date, only limited data regarding morcellation of low-grade uterine neoplasms are available. In the present article, we reported a case of a (morcellator) port-site implantation of a smooth muscle tumor that occurred 6 years after laparoscopic morcellation of a uterine smooth muscle tumor of uncertain potential. This case highlights the effects of intra-abdominal morcellation, even in low-grade uterine neoplasms. Caution should be used when determining techniques for tissue extraction; the potential adverse consequences of morcellation should be more fully explored. PMID- 26851128 TI - Hippocampal cytosolic estrogen receptors regulate fear generalization in females. AB - Generalization of fear responses is a symptom of many anxiety disorders and we have previously demonstrated that female rats generalize fear to a neutral context at a faster rate compared to males. This effect is due in part, to activation of ER and modulation of memory retrieval mechanisms resulting in fear generalization. Given that the effects of estradiol on fear generalization required approximately 24h, our data suggested possible genomic actions on fear generalization. To determine whether these actions were due to cytosolic versus membrane bound receptors, female rats were given infusions of ICI 182,780, a cytosolic estrogen receptor antagonist, into the lateral ventricle or dorsal hippocampus simultaneously with estradiol treatment or with an ER agonist (DPN). Infusions of ICI into the lateral ventricle or the dorsal hippocampus blocked fear generalization induced by peripheral or central treatment with estradiol or DPN, suggesting that estradiol acts through cytosolic ERbeta receptors. In further support of these findings, intracerebroventricular or intra-hippocampal infusions of bovine serum conjugated estradiol (E2-BSA), activating membrane bound estrogen receptors only, did not induce fear generalization. Moreover, rats receiving intra-hippocampal infusions of the ERK/MAPK inhibitor, U0126, continued to display estradiol-induced generalization, again suggesting that membrane-bound estrogen receptors do not contribute to fear generalization. Overall, these data suggest that estradiol-induced enhancements in fear generalization are mediated through activation of cytosolic/nuclear ER within the dorsal hippocampus. This region seems to be an important locus for the effects of estradiol on fear generalization although additional neuroanatomical regions have yet to be identified. PMID- 26851129 TI - Long term exposure to combination paradigm of environmental enrichment, physical exercise and diet reverses the spatial memory deficits and restores hippocampal neurogenesis in ventral subicular lesioned rats. AB - Subiculum is an important structure of the hippocampal formation and plays an imperative role in spatial learning and memory functions. We have demonstrated earlier the cognitive impairment following bilateral ventral subicular lesion (VSL) in rats. We found that short term exposure to enriched environment (EE) did not help to reverse the spatial memory deficits in water maze task suggesting the need for an appropriate enriched paradigm towards the recovery of spatial memory. In the present study, the efficacy of long term exposure of VSL rats to combination paradigm of environmental enrichment (EE), physical exercise and 18 C.W. diet (Combination Therapy - CT) in reversing the spatial memory deficits in Morris water maze task has been studied. Ibotenate lesioning of ventral subiculum produced significant impairment of performance in the Morris water maze and reduced the hippocampal neurogenesis in rats. Post lesion exposure to C.T. restored the hippocampal neurogenesis and improved the spatial memory functions in VSL rats. Our study supports the hypothesis that the combination paradigm is critical towards the development of an enhanced behavioral and cognitive experience especially in conditions of CNS insults and the associated cognitive dysfunctions. PMID- 26851130 TI - The consolidation of inhibitory avoidance memory in mice depends on the intensity of the aversive stimulus: The involvement of the amygdala, dorsal hippocampus and medial prefrontal cortex. AB - Several studies using inhibitory avoidance models have demonstrated the importance of limbic structures, such as the amygdala, dorsal hippocampus and medial prefrontal cortex, in the consolidation of emotional memory. However, we aimed to investigate the role of the amygdala (AMG), dorsal hippocampus (DH) and medial prefrontal cortex (mPFC) of mice in the consolidation of step-down inhibitory avoidance and whether this avoidance would be conditioned relative to the intensity of the aversive stimulus. To test this, we bilaterally infused anisomycin (ANI-40MUg/MUl, a protein synthesis inhibitor) into one of these three brain areas in mice. These mice were then exposed to one of two different intensities (moderate: 0.5mA or intense: 1.5mA) in a step-down inhibitory avoidance task. We found that consolidation of both of the aversive experiences was mPFC dependent, while the AMG and DH were only required for the consolidation of the intense experience. We suggest that in moderately aversive situations, which do not represent a severe physical risk to the individual, the consolidation of aversive experiences does not depend on protein synthesis in the AMG or the DH, but only the mPFC. However, for intense aversive stimuli all three of these limbic structures are essential for the consolidation of the experience. PMID- 26851131 TI - Venous vascular malformation of the floor of mouth masquerading as a dermoid tumor. AB - Venous vascular malformations (VVMs) are described as abnormal post-capillary lesions which exhibit low flow. These are typically malleable and may grow with endocrine fluctuations. A VVM that mimics the classic appearance of dermoid tumor on imaging has never been reported. We encountered a 43-year-old woman with intermittent dysphagia relating to a firm submandibular mass. Physical exam and cross-sectional imaging revealed features consistent with variant dermoid cyst. However, catheter angiography eventually demonstrated a VVM which possessed vessels of variable size and partial thrombosis. We report the case and propose that catheter angiography remains important in cases where vascular malformation is considered. PMID- 26851132 TI - Glial cell morphological and density changes through the lifespan of rhesus macaques. AB - How aging impacts the central nervous system (CNS) is an area of intense interest. Glial morphology is known to affect neuronal and immune function as well as metabolic and homeostatic balance. Activation of glia, both astrocytes and microglia, occurs at several stages during development and aging. The present study analyzed changes in glial morphology and density through the entire lifespan of rhesus macaques, which are physiologically and anatomically similar to humans. We observed apparent increases in gray matter astrocytic process length and process complexity as rhesus macaques matured from juveniles through adulthood. These changes were not attributed to cell enlargement because they were not accompanied by proportional changes in soma or process volume. There was a decrease in white matter microglial process length as rhesus macaques aged. Aging was shown to have a significant effect on gray matter microglial density, with a significant increase in aged macaques compared with adults. Overall, we observed significant changes in glial morphology as macaques age indicative of astrocytic activation with subsequent increase in microglial density in aged macaques. PMID- 26851133 TI - Factors related to telomere length. PMID- 26851135 TI - Do we have enough information to act accordingly? The relation between case volume and results revisited again. PMID- 26851134 TI - Integrated decision strategies for skin sensitization hazard. AB - One of the top priorities of the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM) is the identification and evaluation of non-animal alternatives for skin sensitization testing. Although skin sensitization is a complex process, the key biological events of the process have been well characterized in an adverse outcome pathway (AOP) proposed by the Organisation for Economic Co-operation and Development (OECD). Accordingly, ICCVAM is working to develop integrated decision strategies based on the AOP using in vitro, in chemico and in silico information. Data were compiled for 120 substances tested in the murine local lymph node assay (LLNA), direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT) and KeratinoSens assay. Data for six physicochemical properties, which may affect skin penetration, were also collected, and skin sensitization read-across predictions were performed using OECD QSAR Toolbox. All data were combined into a variety of potential integrated decision strategies to predict LLNA outcomes using a training set of 94 substances and an external test set of 26 substances. Fifty-four models were built using multiple combinations of machine learning approaches and predictor variables. The seven models with the highest accuracy (89-96% for the test set and 96-99% for the training set) for predicting LLNA outcomes used a support vector machine (SVM) approach with different combinations of predictor variables. The performance statistics of the SVM models were higher than any of the non-animal tests alone and higher than simple test battery approaches using these methods. These data suggest that computational approaches are promising tools to effectively integrate data sources to identify potential skin sensitizers without animal testing. Published 2016. This article has been contributed to by US Government employees and their work is in the public domain in the USA. PMID- 26851136 TI - Mass photokeratitis following ultraviolet light exposure at a nightclub. AB - PURPOSE: To report a mass presentation of photokeratitis arising from exposure to an unprotected ultraviolet-B (UV-B) light source. RESULTS: A cluster of 22 patients presented within a 24-h period to a single eye casualty with symptoms of photokeratitis following recent intense UV-B exposure at a local nightclub. Patients were treated with a short course of chloramphenicol, steroid or lubricant eye drops. No patients re-attended. CONCLUSION: This report highlights the hazards of ultraviolet lamps used in public places and the need for strict guidance and enforcement of UV radiation safety protocols to avoid the potential public health risk. PMID- 26851137 TI - Corneal elevation in a large number of myopic Chinese patients. AB - PURPOSE: To establish a normative database for corneal elevation in Chinese myopic patients who underwent refractive surgery, and analyze the association of corneal elevation with sex, age, and ocular parameters. METHODS: A total of 3000 eyes in 1500 patients were evaluated with the Pentacam. Anterior and posterior elevations were measured at the apex and thinnest point. Normative thresholds were defined according to the Tukey method. Univariate and multivariate analyses were performed to assess the association of corneal elevation with sex, age, and ocular parameters. RESULTS: Normal upper limits for corneal elevation in adult Chinese were 4.95MUm, 5.25MUm, 6.2MUm, and 11.0MUm at the anterior apex, anterior thinnest point, posterior apex, and posterior thinnest point, respectively. Thinner corneal pachymetry at the apex and greater anterior corneal astigmatism tended to show greater anterior corneal elevation values. Younger age, greater anterior corneal astigmatism, lower anterior and posterior keratometry, and shallower anterior chamber depth resulted in greater posterior corneal elevation values. CONCLUSIONS: Locally derived thresholds may offer higher sensitivity and specificity when screening eyes for myopic refractive surgery, and keratoconic and post-orthokeratology eyes. Anterior and posterior corneal elevation at the apex and thinnest point were associated significantly with anterior corneal astigmatism, showing a positive correlation. PMID- 26851138 TI - Evaluation of pigment location in tinted soft contact lenses. AB - PURPOSE: The purpose of this study was to investigate efficient methods to evaluate the pigment layer location of tinted soft contact lenses and to assess various lens products on the market using those methods. METHODS: Two types of tinted soft contact lenses with known pigment location embedded or back surface were manufactured and examined. Light microscopy (LM), focused ion beam milling and scanning electron microscopy (FIB-SEM), and Fourier-domain optical coherence tomography (FD-OCT) were used to examine the pigment layer. Lens surface roughness was also measured using atomic force microscopy. In the second part of the experiment, pigment location and surface roughness of a clear lens (Lens A) and eight commercially-available tinted soft contact lenses (Lens B-I) were evaluated using FIB-SEM and FD-OCT. RESULTS: Pigment location could be reliably determined with FIB-SEM and FD-OCT. With LM, 40% of the lens sections were broken or deformed during slide preparation. The pigment particles in Lens B were buried below the front surface and there were no significant differences of roughness between the front and back surfaces. However, all tinted lenses with surface pigment had significant difference of roughness between front and back surfaces at the pigmented area. CONCLUSION: The FIB-SEM and FD-OCT could reliably locate the pigment layer of tinted soft contact lenses. In addition, lens surface roughness was influenced by pigment layer location. PMID- 26851139 TI - The diagnostic ability of procalcitonin and interleukin-6 to differentiate infectious from noninfectious systemic inflammatory response syndrome and to predict mortality. AB - PURPOSE: The purpose of the study was to quantify the ability of procalcitonin (PCT) and interleukin-6 (IL-6) to differentiate noninfectious systemic inflammatory response syndrome (SIRS) and sepsis and to predict hospital mortality. MATERIALS: We recruited consecutively adult patients with SIRS admitted to an intensive care unit. They were divided into sepsis and noninfectious SIRS based on clinical assessment with or without positive cultures. Concentrations of PCT and IL-6 were measured daily over the first 3 days. RESULTS: A total of 239 patients were recruited, 164 (68.6%) had sepsis, and 68 (28.5%) died in hospital. The PCT levels were higher in sepsis compared with noninfectious SIRS throughout the 3-day period (P < .0001). On admission, PCT concentration was diagnostic of sepsis (area under the curve of 0.63 [0.55 0.71]), and IL-6 was predictive of mortality, (area under the curve of 0.70 [0.62 0.78]). Peak IL-6 concentration improved the risk assessment of Sequential Organ Failure Assessment (SOFA) score for prediction of mortality among those who went on to die by an average of 5% and who did not die by 2% CONCLUSIONS: Procalcitonin measured on intensive care unit admission was diagnostic of sepsis, and IL-6 was predictive of mortality. Addition of IL-6 concentration to SOFA score improved risk assessment for prediction of mortality. Future studies should include clinical indices, for example, SOFA score, for prognostic evaluation of biomarkers. PMID- 26851140 TI - Serial measurements of troponin and echocardiography in patients with moderate-to severe acute respiratory distress syndrome. AB - PURPOSE: To assess the clinical significance of serial troponin I levels (measured in the first 72 hours from admission) in 42 consecutive patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Echocardiography and electrocardiogram testings were serially performed in the time window. MATERIALS AND METHODS: Troponin I was measured every 12 hours in the first 72 hours from intensive care unit (ICU) admission. Echocardiography and electrocardiogram testings were serially performed in the same time window to clinically interpret Tn I levels. RESULTS: Patients with admission positive Tn I (38.1%) showed higher values of systolic pulmonary hypertension (P = .013) associated with significantly lower values of tricuspid annular plane excursion (P = .011). Twenty-five patients (25/42, 59.5%) exhibited positive peak Tn I and at second echocardiographic assessment exhibited significant lower tricuspid annular plane excursion values (P = .005). At stepwise regression analysis the following variables were an independent predictor for in-ICU mortality: Pco2 (OR 1.08, 95% CI 1.011-1.161, P = .023), systolic pulmonary arterial hypertension (OR 0.83, 95% CI 0.701-0.977, P = .002), log peak Tn I (OR 3.56, 95% CI 1.045-12.132, P = .042). CONCLUSIONS: In moderate-to-severe ARDS, serial troponin I assessment together with echocardiography evaluation helped to identify a subgroup at higher risk for in-ICU death. Moreover, troponin release can be related to right ventricular dysfunction, thus highlighting the clinical role of echocardiography in ARDS patients. PMID- 26851141 TI - Genome-wide investigation of schizophrenia associated plasma Ndel1 enzyme activity. AB - Ndel1 is a DISC1-interacting oligopeptidase that cleaves in vitro neuropeptides as neurotensin and bradykinin, and which has been associated with both neuronal migration and neurite outgrowth. We previously reported that plasma Ndel1 enzyme activity is lower in patients with schizophrenia (SCZ) compared to healthy controls (HCs). To our knowledge, no previous study has investigated the genetic factors associated with the plasma Ndel1 enzyme activity. In the current analyses, samples from 83 SCZ patients and 92 control subjects that were assayed for plasma Ndel1 enzyme activity were genotyped on Illumina Omni Express arrays. A genetic relationship matrix using genome-wide information was then used for ancestry correction, and association statistics were calculated genome-wide. Ndel1 enzyme activity was significantly lower in patients with SCZ (t=4.9; p<0.001) and was found to be associated with CAMK1D, MAGI2, CCDC25, and GABGR3, at a level of suggestive significance (p<10(-6)), independent of the clinical status. Then, we performed a model to investigate the observed differences for case/control measures. 2 SNPs at region 1p22.2 reached the p<10(-7) level. ZFPM2 and MAD1L1 were the only two genes with more than one hit at 10(-6) order of p value. Therefore, Ndel1 enzyme activity is a complex trait influenced by many different genetic variants that may contribute to SCZ physiopathology. PMID- 26851142 TI - The affective reactivity of psychotic speech: The role of internal source monitoring in explaining increased thought disorder under emotional challenge. AB - Thought disorder (TD) has been shown to vary in relation to negative affect. Here we examine the role internal source monitoring (iSM, i.e. ability to discriminate between inner speech and verbalized speech) in TD and whether changes in iSM performance are implicated in the affective reactivity effect (deterioration of TD when participants are asked to talk about emotionally-laden topics). Eighty patients diagnosed with schizophrenia-spectrum disorder and thirty healthy controls received interviews that promoted personal disclosure (emotionally salient) and interviews on everyday topics (non-salient) on separate days. During the interviews, participants were tested on iSM, self-reported affect and immediate auditory recall. Patients had more TD, poorer ability to discriminate between inner and verbalized speech, poorer immediate auditory recall and reported more negative affect than controls. Both groups displayed more TD and negative affect in salient interviews but only patients showed poorer performance on iSM. Immediate auditory recall did not change significantly across affective conditions. In patients, the relationship between self-reported negative affect and TD was mediated by deterioration in the ability to discriminate between inner speech and speech that was directed to others and socially shared (performance on the iSM) in both interviews. Furthermore, deterioration in patients' performance on iSM across conditions significantly predicted deterioration in TD across the interviews (affective reactivity of speech). Poor iSM is significantly associated with TD. Negative affect, leading to further impaired iSM, leads to increased TD in patients with psychosis. Avenues for future research as well as clinical implications of these findings are discussed. PMID- 26851143 TI - Measuring the capacity for auditory system plasticity: An examination of performance gains during initial exposure to auditory-targeted cognitive training in schizophrenia. AB - Auditory-Targeted Cognitive Training (ATCT), which aims to improve auditory information processing efficiency, has shown great promise for remediating cognitive deficits in schizophrenia (SZ). However, there is substantial heterogeneity in the degree of cognitive gains made during ATCT, and some patients show negligible benefit after completing therapeutic doses of training. Identifying individual differences that can be measured early in the course of ATCT and that predict subsequent cognitive benefits from the intervention is therefore important. The present study calculated a variety of performance metrics during the initial hour of exposure to ATCT Sound Sweeps, a frequency discrimination time-order judgment task, and investigated the relationships of these metrics to demographic, clinical, and cognitive characteristics of SZ patients. Thirty-seven SZ outpatients completed measures of auditory attention, working memory, verbal memory, and executive functioning, followed by 1h of Sound Sweeps training. Performance metrics, calculated after the first training level, the first training stage (Levels 1-4), and the entire hour of training included baseline and best auditory processing speed (APS) scores, as well as percent improvement in APS after training. The number of training levels completed by each participant was also calculated. Baseline and best APS correlated with performance in all cognitive domains, whereas APS improvements only correlated with verbal memory. Number of training levels completed was marginally associated with auditory attention only. CONCLUSIONS: Sound Sweeps performance correlates with a range of neurocognitive abilities. APS improvement may provide a particularly sensitive index of "plasticity potential" within the neural network underlying verbal learning and memory. PMID- 26851145 TI - Prevention of Cataract by Statins. PMID- 26851144 TI - Prevalence of Body Dysmorphic Disorder Symptoms and Body Weight Concerns in Patients Seeking Abdominoplasty. AB - BACKGROUND: Body dysmorphic disorder (BDD) is one of the most common psychiatric conditions found in patients seeking cosmetic surgery, and body contouring surgery is most frequently sought by patients with BDD. OBJECTIVES: To estimate the prevalence and severity of BDD symptoms in patients seeking abdominoplasty. METHODS: Ninety patients of both sexes were preoperatively divided into two groups: patients with BDD symptoms (n = 51) and those without BDD symptoms (n = 39) based both on the Body Dysmorphic Disorder Examination (BDDE) and clinical assessment. Patients in the BDD group were classified as having mild to moderate or severe symptoms, according to the BDDE. Body weight and shape concerns were assessed using the Body Shape Questionnaire (BSQ). RESULTS: The prevalence of BDD symptoms was 57%. There were significant associations between BDD symptoms and degree of body dissatisfaction, level of preoccupation with physical appearance, and avoidance behaviors. Mild to moderate and severe symptoms of BDD were present in 41% and 59% of patients, respectively, in the BDD group. It was found that the more severe the symptoms of BDD, the higher the level of concern with body weight and shape (P < .001). Patients having distorted self-perception of body shape, or distorted comparative perception of body image were respectively 3.67 or 5.93 times more likely to show more severe symptoms of BDD than those with a more accurate perception. CONCLUSIONS: Candidates for abdominoplasty had a high prevalence of BDD symptoms, and body weight and shape concerns were associated with increased symptom severity. PMID- 26851146 TI - Serum Osmolality and Postdischarge Outcomes After Hospitalization for Heart Failure. AB - Serum osmolality may fluctuate with neurohormonal activation and in response to certain therapeutics in patients with heart failure (HF). The clinical relevance of osmolality in patients with HF has not been defined. In this post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan trial, we analyzed serum osmolality measured at discharge in 3,744 patients hospitalized for HF and reduced ejection fraction (EF <=40%). Median follow-up was 9.9 months. The association between discharge osmolality and all cause mortality (ACM) and composite cardiovascular mortality or HF hospitalization was nonlinear; and thus, patients were divided into low (<=284), normal (285 to 300), and high (>=300 mOsm/kg) osmolality. Median serum osmolality at discharge was 297 (290 to 304) mOsm/kg. Patients in the low osmolality group (n = 454,12.1%) were more likely to be younger, men, have lower rates of hypertension, coronary artery disease, chronic kidney disease, diabetes, and have lower serum sodium, creatinine, systolic blood pressure, and EF (all p <0.001). Low discharge osmolality was associated with higher ACM (low 29.3%; normal 23.6%; high 25.2%; p = 0.04) and the composite endpoint (low 45.6%; normal 39.3%; high 41.8%; p = 0.04). After risk adjustment, a 15 mOsm/kg decrease in osmolality was predictive of higher ACM (hazard ratio 1.61, 95% CI 1.19 to 2.17) and the composite endpoint (hazard ratio 1.37, 95% CI 1.06 to 1.75) in the low osmolality group. These associations were not seen in patients with normal or high osmolality. Interaction analyses for tolvaptan treatment were nonsignificant (p >0.4). In conclusion, low discharge serum osmolality was independently predictive of worse postdischarge mortality and readmission. Further study is required to clarify the clinical utility of serum osmolality in hospitalized patients with HF. PMID- 26851147 TI - Coronoid process and residual ankylotic mass as an autograft in the management of ankylosis of the temporomandibular joint in young adolescent patients: a retrospective clinical investigation. AB - The aim of this non-randomised investigation was to assess the feasibility of using autogenous grafts (such as coronoid process and the resected ankylotic mass) in reconstruction of the condyle after gap arthroplasty for ankylosis of the temporomandibular joint (TMJ). Sixteen patients (23 joints) operated on between 2007 and 2009 were studied and postoperative measurements of maximum interincisal opening, bite force, range of movement, and infection were recorded. After a mean (SD) follow up of 55 (2.25) months mouth opening improved from 3 (3.84) mm to 33 (1.66) mm in patients treated with coronoid graft, while in patients treated with an ankylotic mass after a mean (SD) follow up of 58 (1.58) months it increased from 4 (2.64) mm to 26 (8.04) mm. Bite force six months postoperatively ranged from 18.25kg/cm(2) - 27.5kg/cm(2) after reconstruction with the coronoid process and 18.5kg/cm(2) - 23.25kg/cm(2) after reconstruction with the ankylotic mass. One patient developed reankylosis postoperatively and another developed infection, in both of which the ankylotic mass had been used. Both were managed successfully. Both the ankylotic mass and the coronoid process gave satisfactory results and seem to be options for reconstruction. However, the coronoid process graft was better than residual ankylotic mass in terms of masticatory efficiency, bite force, and range of movement. PMID- 26851148 TI - Transmigration of mandibular cuspids: review of published reports and description of nine new cases. AB - We have reviewed all documented cases of mandibular canine transmigration from 1951 (when to our knowledge the first case was published) to 2015, and retrospectively evaluated nine further sequential cases of transmigrating mandibular canines in one hospital by analysing relevant data, including patients' age and sex, presence of retained deciduous canines, radiographic changes, coexisting systemic diseases, and treatment. Transmigration of a mandibular canine is a rare anomaly of eruption, and extraction is the usual treatment. The nine new patients were aged from 16 -48 years, eight of the transmigrated canines were unilateral, and one patient had them bilaterally. They were all completely impacted. Four were retained primary teeth, and five exfoliated primary canines. Eight had no associated radiographic or clinical abnormalities, while one patient had an associated odontoma. Six mandibular canines were removed and three kept under observation. Early detection of transmigrated canines gives the opportunity to monitor their development, which may improve prognosis and treatment. PMID- 26851149 TI - Underestimation of myocardial blood flow by dynamic perfusion CT: Explanations by two-compartment model analysis and limited temporal sampling of dynamic CT. AB - PURPOSE: Previous studies using dynamic perfusion CT and volume perfusion CT (VPCT) software consistently underestimated the stress myocardial blood flow (MBF) in normal myocardium to be 1.1-1.4 ml/min/g, whilst the O 15-water PET studies demonstrated the normal stress MBF of 3-5 ml/min/g. We hypothesized that the MBF determined by VPCT (MBF-VPCT) is actually presenting the blood-to myocardium transfer constant, K1. In this study, we determined K1 using Patlak plot (K1-Patlak) and compared the results with MBF-VPCT. MATERIAL AND METHODS: 17 patients (66 +/- 9 years, 7 males) with suspected coronary artery disease (CAD) underwent stress dynamic perfusion CT, followed by rest coronary CT angiography (CTA). Arterial input and myocardial output curves were analyzed with Patlak plot to quantify myocardial K1. Significant CAD was defined as >50% stenosis on CTA. A simulation study was also performed to investigate the influence of limited temporal sampling in dynamic CT acquisition on K1 using the undersampling data generated from MRI. RESULTS: There were 3 patients with normal CTA, 7 patients with non-significant CAD, and 7 patients with significant CAD. K1-patlak was 0.98 +/- 0.35 (range 0.22-1.67) ml/min/g, whereas MBF-VPCT was 0.83 +/- 0.23 (range 0.34-1.40) ml/min/g. There was a linear relationship between them: (MBF-VPCT) = 0.58 x (K1-patlak) + 0.27 (r(2) = 0.65, p < 0.001). The simulation study done on MRI data demonstrated that Patlak plot substantially underestimated true K1 by 41% when true K1 was 2.0 ml/min/g with the temporal sampling of 2RR for arterial input and 4RR for myocardial output functions. CONCLUSIONS: The results of our study are generating hypothesis that MBF-VPCT is likely to be calculating K1 patlak equivalent, not MBF. In addition, these values may be substantially underestimated because of limited temporal sampling rate. PMID- 26851150 TI - Mutated tau, amyloid and neuroinflammation in Alzheimer disease-A brief review. AB - This review discussed the importance of mutated tau, amyloid and neuroinflammatory factors and microglia in Alzheimer disease. In particular tau, CD4 and TNF alpha were included in the review and the colocalizations of these factors were highlighted. It is important to realize the Alzheimer disease may result from the interactions of these factors. Some of these factors may coexist at the same region and at the same time e.g. mutated tau and amyloid in plaques. A summary scheme of etiology leading to the disease was included. PMID- 26851151 TI - Study of clitoral hood anatomy in the pediatric population. AB - INTRODUCTION AND AIMS: Pediatric female genitalia size and morphology have not previously been well described. The aims of this study were to create a standard reference for the anterior vulval structures, and examine the relationship between the clitoral hood and labia minora. METHOD: Female patients between 0 and 16 years of age, and with normal external genitalia had the following measurements taken: length of clitoral hood, length of sides of clitoral hood, clitoral diameter, apex of clitoral hood to base of pubic symphysis, apex of clitoral hood to urethral orifice, distance of clitoral hood to labia majora, and length and depth of labia minora. Qualitative descriptors of the clitoral hood and labia were recorded. Patients were grouped into age ranges for analysis: 0-3 years, 4-8 years, 9-12 years, and 13-16 years. RESULTS: Fifty-eight girls were examined. There was a linear relationship between age and genital structure size. In the majority of patients, the labia minora converged under the clitoral glans, separate to the clitoral hood. Four shapes of clitoral hood were observed: horseshoe, trumpet, coffee bean, and tent. DISCUSSION: This study observed great variation in size and morphology of pediatric female genitalia, which is in keeping with other studies. The study was limited by ability to recruit older patients to the study (girls aged 11-16 years) and, therefore, there were lower numbers in this age category. However, the trends that were observed were present in both younger and older girls. CONCLUSION: External genitalia size and morphology are varied in the pediatric female population. The clitoral hood and labia minora were observed to be distinctly separate structures. This study provides a reference for surgeons undertaking genital reconstruction procedures. The study demonstrated that the clitoral hood and labia minora are anatomically distinct structures. PMID- 26851152 TI - Preventing obesity among Brazilian adolescent girls: Six-month outcomes of the Healthy Habits, Healthy Girls-Brazil school-based randomized controlled trial. AB - BACKGROUND: School-based trials to prevent and reduce prevalence of pediatric obesity in low-income countries are necessary. In Brazil, addressing adolescent obesity is a public health priority. OBJECTIVE: To evaluate the impact of a group randomized controlled trial involving a 6-month multicomponent school-based obesity prevention program targeting adolescent girls. METHODS: The Healthy Habits, Healthy Girls-Brazil program recruited participants (n=253; 16.05+/-0.05 years) from ten eligible public technical schools in Sao Paulo, Brazil. The program was adapted from an Australian intervention study, which is based on the Social Cognitive Theory. The primary outcome measure was body mass index (BMI), and secondary outcomes included BMI z score, waist circumference, and various sedentary and dietary health-related behaviours. RESULTS: Although changes in BMI were not statistically significant, differences favored the intervention group (adjusted mean difference, -0.26kg/m(2),se SE=0.018, p=0.076). Statistically significant intervention effects were found for waist circumference (-2.28cm; p=, p=0.01), computer screen time on the weekends (0.63h/day, p; p=0.02), total sedentary activities on the weekends (-0.92h/day, p<0.01), and vegetable intake (1.16servings/day, p=0.01). CONCLUSION: These findings provide some evidence for the benefit of a school-based intervention to prevent unhealthy weight gain in adolescent girls living in low-income communities. PMID- 26851153 TI - Smoke and Hormone Mirrors: Action and Evolution of Karrikin and Strigolactone Signaling. AB - Karrikins and strigolactones are two classes of butenolide molecules that have diverse effects on plant growth. Karrikins are found in smoke and strigolactones are plant hormones, yet both molecules are likely recognized through highly similar signaling mechanisms. Here we review the most recent discoveries of karrikin and strigolactone perception and signal transduction. Two paralogous alpha/beta hydrolases, KAI2 and D14, are respectively karrikin and strigolactone receptors. D14 acts with an F-box protein, MAX2, to target SMXL/D53 family proteins for proteasomal degradation, and genetic data suggest that KAI2 acts similarly. There are striking parallels in the signaling mechanisms of karrikins, strigolactones, and other plant hormones, including auxins, jasmonates, and gibberellins. Recent investigations of host perception in parasitic plants have demonstrated that strigolactone recognition can evolve following gene duplication of KAI2. PMID- 26851154 TI - The potential of computed crystal energy landscapes to aid solid-form development. AB - Solid-form screening to identify all solid forms of an active pharmaceutical ingredient (API) has become increasingly important in ensuring the quality by design of pharmaceutical products and their manufacturing processes. However, despite considerable enlargement of the range of techniques that have been shown capable of producing novel solid forms, it is possible that practically important forms might not be found in the short timescales currently allowed for solid-form screening. Here, we report on the state-of-the-art use of computed crystal energy landscapes to complement pharmaceutical solid-form screening. We illustrate how crystal energy landscapes can help establish molecular-level understanding of the crystallization behavior of APIs and enhance the ability of solid-form screening to facilitate pharmaceutical development. PMID- 26851155 TI - Staphylococcus aureus lactate- and malate-quinone oxidoreductases contribute to nitric oxide resistance and virulence. AB - Staphylococcus aureus is a Gram-positive pathogen that resists many facets of innate immunity including nitric oxide (NO.). Staphylococcus aureus NO-resistance stems from its ability to evoke a metabolic state that circumvents the negative effects of reactive nitrogen species. The combination of l-lactate and peptides promotes S. aureus growth at moderate NO-levels, however, neither nutrient alone suffices. Here, we investigate the staphylococcal malate-quinone and l-lactate quinone oxidoreductases (Mqo and Lqo), both of which are critical during NO stress for the combined utilization of peptides and l-lactate. We address the specific contributions of Lqo-mediated l-lactate utilization and Mqo-dependent amino acid consumption during NO-stress. We show that Lqo conversion of l-lactate to pyruvate is required for the formation of ATP, an essential energy source for peptide utilization. Thus, both Lqo and Mqo are essential for growth under these conditions making them attractive candidates for targeted therapeutics. Accordingly, we exploited a modelled Mqo/Lqo structure to define the catalytic and substrate-binding residues.We also compare the S. aureus Mqo/Lqo enzymes to their close relatives throughout the staphylococci and explore the substrate specificities of each enzyme. This study provides the initial characterization of the mechanism of action and the immunometabolic roles for a newly defined staphylococcal enzyme family. PMID- 26851156 TI - Relationship of N-Terminal fragment of Pro-B-Type Natriuretic Peptide and copeptin with erythrocytes-related parameters: A population-based study. AB - BACKGROUND: Plasma levels of natriuretic peptides (NP) have been inversely related to hemoglobin (Hb) concentration in prior studies. However, the mechanism underlying this association remains unclear. We aimed to obtain further insights into potential mechanisms for this correlation in a cohort of healthy adults. METHODS: A population-based study was performed among 2113 healthy adults aged 25 41years. Relationships of N-Terminal fragment of Pro-B-Type Natriuretic Peptide (NT-proBNP) or copeptin with volume-dependent (Hb, hematocrit (Hct), erythrocyte count (EC), mean corpuscular Hb concentration (MCHC)) and volume-independent (mean corpuscular volume (MCV), mean corpuscular Hb (MCH)) erythrocyte-related parameters were assessed using sex-specific multivariable linear regression analyses. RESULTS: The median age was 36.7years. Median NT-proBNP (ng/L) levels were 49.5 and 20 among women and men, respectively (p<0.0001). Mean (standard deviation) Hb (g/L) levels were 130.1(9.1) and 149.7(8.6) among women and men, respectively (p<0.0001). Among men, multivariable adjusted beta-coefficients (95% confidence interval) for NT-proBNP were -1.68 (-2.36; -1.01), p<0.0001 for Hb; 0.38 (-0.57; -0.20), p<0.0001 for Hct; -0.06 (-0.09; -0.04), p<0.0001 for EC; 0.78 (-1.50; -0.07), p=0.03 for MCHC; 0.26 (-0.04; 0.56), p=0.09 for MCV; and 0.03 (-0.08; 0.14), p=0.61 for MCH. For copeptin, these relationships were 1.36 (0.39; 2.32), p=0.006; 0.41 (0.15; 0.68), p=0.002; 0.06 (0.02; 0.09), p=0.002; 0.17 (-1.19; 0.86), p=0.75; -0.12 (-0.55; 0.31), p=0.58 and -0.05 (-0.21; 0.10), p=0.52. Similar results were observed among women. CONCLUSIONS: We found significant relationships of NT-proBNP and copeptin with volume-dependent but not volume-independent erythrocyte-related parameters, suggesting that hemodilution may at least in part explain these associations. PMID- 26851157 TI - Reference gene selection for in vitro cell-free DNA analysis and gene expression profiling. AB - OBJECTIVES: (i) To optimize cell-free DNA (cfDNA) and mRNA quantification using eight housekeeping genes (HKGs), (ii) to determine if there is a difference in the occurrence of HKGs in the cfDNA and mRNA of normal cells and cancer cells, and (iii) to investigate whether there is some selectivity involved in the release of cfDNA. DESIGN AND METHODS: cfDNA was isolated directly from the growth medium of 3 cultured cancer cell lines and one non-malignant, primary cell line. At the same time interval, mRNA was isolated from these cells and cDNA was synthesized. CfDNA and cDNA were then amplified with real-time PCR utilizing eight different HKGs. RESULTS: For all cell lines tested, Beta-actin (ACTB) is the most appropriate HKG to use as a control for cfDNA and mRNA quantification. There was no clear difference in the occurrence of HKGs between cancer cells and healthy cells. Lastly, there is a consistent and distinct difference between the mRNA expression and cfDNA of all cell lines. CONCLUSIONS: This study reveals a new candidate HKG for a robust control in cfDNA analysis and gene expression profiling, and should be considered for optimal analysis. Furthermore, results indicate that cfDNA is selectively released from cells into culture medium. PMID- 26851158 TI - Transcatheter Therapy for Hepatic Malignancy: Standardization of Terminology and Reporting Criteria. PMID- 26851159 TI - Achieving self-management of prophylactic treatment in adolescents: The case of haemophilia. AB - OBJECTIVE: Adolescents with a chronic disorder, such as haemophilia, need to attain responsibility for their disease. The aim was to gain insight into how adolescents achieve self-management of prophylactic treatment. METHODS: In three Dutch Haemophilia Treatment Centres, adolescents (10-25 years) received structured questions on treatment responsibility and self-management (pre specified definitions) during routine nursing consultation. RESULTS: In total, 155 interviews were performed in 100 patients (median age 14.4 years). Self infusion was initiated at a median age of 12.3 years (IQR 11.5-13.0) and self management was achieved 9.6 years later, at a median age of 22.6 years. This process included three phases coinciding with known stages of adolescence. In early adolescence, patients acquired the technique of self-infusion (12.3 years) leading to independent self-infusion in middle adolescence (17.2 years). In late adolescence, patients demonstrated an increase in more complex skills, such as bleeding management and communication with the haemophilia physician (19.9-22.6 years). CONCLUSION: Although, the first steps in self-management with regard to self-infusion are taken in early adolescence, complete self-management was achieved in late adolescence after almost 10 years. PRACTICE IMPLICATIONS: Insight in this transitional process helps to provide individualized support and emphasizes the need for continued education with regard to self-management skills. PMID- 26851160 TI - Dealing with patients in healthcare: A self-assessment tool. AB - OBJECTIVE: This study aimed to investigate how healthcare personnel self-evaluate their ability to relate to patients in day-to-day practice from a patient centered perspective, and to test the psychometric properties of a questionnaire developed to assess it. METHODS: A sample of 600 healthcare personnel, recruited among eight hospitals in various parts of Italy, completed the 16-item Provider Patient Relationship Questionnaire (PPRQ). A sample of 50 nurses answered the PPRQ twice, at a four-week interval. The PPRQ validity, reliability and susceptibility to social desirability were tested. RESULTS: PPRQ showed good reliability and structural validity, with four first-order factors: effective communication, interest in the patient's agenda, empathy, and patient involvement in care. Correlation with social desirability was negligible. Participants rated themselves as highly competent in communicating with patients, but less interested in involving the patient in care and in the patient's agenda. Differences in PPRQ dimensions were found between groups based on job type and geographic area. CONCLUSION: PPRQ is a brief self-report measure of the provider patient relationship with promising psychometric properties in this sample. PRACTICE IMPLICATIONS: PPRQ has potential value in promoting a self-reflecting learning environment, whether through training or day-to-day practice. PMID- 26851161 TI - The biphasic function of microglia in ischemic stroke. AB - Microglia are brain resident macrophages originated from primitive progenitor cells in the yolk sac. Microglia can be activated within hours and recruited to the lesion site. Traditionally, microglia activation is considered to play a deleterious role in ischemic stroke, as inhibition of microglia activation attenuates ischemia induced brain injury. However, increasing evidence show that microglia activation is critical for attenuating neuronal apoptosis, enhancing neurogenesis, and promoting functional recovery after cerebral ischemia. Differential polarization of microglia could likely explain the biphasic role of microglia in ischemia. We comprehensively reviewed the mechanisms involved in regulating microglia activation and polarization. The latest discoveries of microRNAs in modulating microglia function are discussed. In addition, the interaction between microglia and other cells including neurons, astrocytes, oligodendrocytes, and stem cells were also reviewed. Future therapies targeting microglia may not exclusively aim at suppressing microglia activation, but also at modulating microglia polarization at different stages of ischemic stroke. More work is needed to elucidate the cellular and molecular mechanisms of microglia polarization under ischemic environment. The roles of microRNAs and transplanted stem cells in mediating microglia activation and polarization during brain ischemia also need to be further studied. PMID- 26851162 TI - The European Federation of Organisations for Medical Physics Policy Statement No. 6.1: Recommended Guidelines on National Registration Schemes for Medical Physicists. AB - This EFOMP Policy Statement is an update of Policy Statement No. 6 first published in 1994. The present version takes into account the European Union Parliament and Council Directive 2013/55/EU that amends Directive 2005/36/EU on the recognition of professional qualifications and the European Union Council Directive 2013/59/EURATOM laying down the basic safety standards for protection against the dangers arising from exposure to ionising radiation. The European Commission Radiation Protection Report No. 174, Guidelines on Medical Physics Expert and the EFOMP Policy Statement No. 12.1, Recommendations on Medical Physics Education and Training in Europe 2014, are also taken into consideration. The EFOMP National Member Organisations are encouraged to update their Medical Physics registration schemes where these exist or to develop registration schemes taking into account the present version of this EFOMP Policy Statement (Policy Statement No. 6.1"Recommended Guidelines on National Registration Schemes for Medical Physicists"). PMID- 26851163 TI - The European Federation of Organisations for Medical Physics Policy Statement No. 10.1: Recommended Guidelines on National Schemes for Continuing Professional Development of Medical Physicists. AB - Continuing Professional Development (CPD) is vital to the medical physics profession if it is to embrace the pace of change occurring in medical practice. As CPD is the planned acquisition of knowledge, experience and skills required for professional practice throughout one's working life it promotes excellence and protects the profession and public against incompetence. Furthermore, CPD is a recommended prerequisite of registration schemes (Caruana et al. 2014) and is implied in the Council Directive 2013/59/EURATOM (EU BSS) and the International Basic Safety Standards (BSS). It is to be noted that currently not all national registration schemes require CPD to maintain the registration status necessary to practise medical physics. Such schemes should consider adopting CPD as a prerequisite for renewing registration after a set period of time. This EFOMP Policy Statement, which is an amalgamation and an update of the EFOMP Policy Statements No. 8 and No. 10, presents guidelines for the establishment of national schemes for CPD and activities that should be considered for CPD. PMID- 26851164 TI - Evaluation of a new transperineal ultrasound probe for inter-fraction image guidance for definitive and post-operative prostate cancer radiotherapy. AB - PURPOSE: The aim of this study was to evaluate a new system based on transperineal ultrasound (TP-US) acquisitions for prostate and post-prostatectomy pre-treatment positioning by comparing this device to cone-beam computed tomography (CBCT). METHODS: The differences between CBCT/CT and TP-US/TP-US registrations were analyzed on 427 and 453 sessions for 13 prostate and 14 post prostatectomy patients, respectively. The inter-operator variability (IOV) of the registration process, and the impact and variability of the probe pressure were also evaluated. RESULTS: CBCT and TP-US shift agreements at +/- 5 mm were 76.6%, 95.1%, 96.3% and 90.3%, 85.0%, 97.6% in anterior-posterior, superior-inferior and left-right directions, for prostate and post-prostatectomy patients, respectively. IOV values were similar between the 2 modalities. Displacements above 5 mm due to strong pressures were observed on both localizations, but such pressures were rarely reproduced during treatment courses. CONCLUSIONS: High concordance between CBCT/CT and TP-US/TP-US localization of prostates or prostatic beds was found in this study. TP-US based prepositioning is a feasible method to ensure accurate treatment delivery, and represents an attractive alternative to invasive and/or irradiating imaging modalities. PMID- 26851165 TI - Implantation of healthy matrix-embedded endothelial cells rescues dysfunctional endothelium and ischaemic tissue in liver engraftment. AB - OBJECTIVE: Liver transplantation is limited by ischaemic injury which promotes endothelial cell and hepatocyte dysfunction and eventually organ failure. We sought to understand how endothelial state determines liver recovery after hepatectomy and engraftment. DESIGN: Matrix-embedded endothelial cells (MEECs) with retained healthy phenotype or control acellular matrices were implanted in direct contact with the remaining median lobe of donor mice undergoing partial hepatectomy (70%), or in the interface between the remaining median lobe and an autograft or isograft from the left lobe in hepatectomised recipient mice. Hepatic vascular architecture, DNA fragmentation and apoptosis in the median lobe and grafts, serum markers of liver damage and phenotype of macrophage and lymphocyte subsets in the liver after engraftment were analysed 7 days post-op. RESULTS: Healthy MEECs create a functional vascular splice in donor and recipient liver after 70% hepatectomy in mouse protecting these livers from ischaemic injury, hepatic congestion and inflammation. Macrophages recruited adjacent to the vascular nodes into the implants switched to an anti-inflammatory and regenerative profile M2. MEECs improved liver function and the rate of liver regeneration and prevented apoptosis in donor liver lobes, autologous grafts and syngeneic engraftment. CONCLUSIONS: Implants with healthy endothelial cells rescue liver donor and recipient endothelium and parenchyma from ischaemic injury after major hepatectomy and engraftment. This study highlights endothelial hepatocyte crosstalk in hepatic repair and provides a promising new approach to improve regenerative medicine outcomes and liver transplantation. PMID- 26851167 TI - Prevalence of Trypanosoma cruzi's Discrete Typing Units in a cohort of Latin American migrants in Spain. AB - Chagas disease is caused by the protozoan Trypanosoma cruzi. This is an endemic disease in the Americas, but increased migration to Europe has made it emerge in countries where it was previously unknown, being Spain the second non endemic country in number of patients. T. cruzi is a parasite with a wide genetic diversity, which has been grouped by consensus into 6 Discrete Typing Units (DTUs) affecting humans. Some authors have linked these DTUs either to a specific epidemiological context or to the different clinical presentations. Our main objective was to describe the T. cruzi DTUs identified from a population of chronically infected Latin American migrants attending a reference clinic in Madrid. 149 patients meeting this condition were selected for the study. Molecular characterization was performed by an algorithm that combines PCR of the intergenic region of the mini exon-gene, the 24Salpha and 18S regions of rDNA and the variable region of the satellite DNA. A descriptive analysis was performed and associations between geographical/clinical data and the different DTUs were tested. DTUs could be determined in 105 out of 149 patients, 93.3% were from Bolivia, 67.7% were women and median age was 35 years (IQR 29-44). The most common DTU found was TcV (58; 55.2%), followed by TcIV (17; 16.2%), TcII (10; 9.5%) and TcI (4; 3.8%). TcIII and TcVI were not identified from any patient, and 15.2% patients presented mixed infections. In addition, we determined DTUs after treatment in a subset of patients. In 57% patients had different DTUs before and after treatment. DTUs distribution from this study indicates active transmission of T. cruzi is occurring in Bolivia, in both domestic and sylvatic cycles. TcIV was confirmed as a cause of chronic human disease. The current results indicate no correlation between DTU and any specific clinical presentation associated with Chagas disease, nor with geographical origin. Treatment with benznidazole does not always clear T. cruzi's genetic material from blood, and DTUs detected in the same patient may vary over time indicating that polyparasitism is frequent. PMID- 26851166 TI - Insight into phagocytosis of mature sexual (gametocyte) stages of Plasmodium falciparum using a human monocyte cell line. AB - During natural infection malaria parasites are injected into the bloodstream of a human host by the bite of an infected female Anopheles mosquito. Both asexual and mature sexual stages of Plasmodium circulate in the blood. Asexual forms are responsible for clinical malaria while sexual stages are responsible for continued transmission via the mosquitoes. Immune responses generated against various life cycle stages of the parasite have important roles in resistance to malaria and in reducing malaria transmission. Phagocytosis of free merozoites and erythrocytic asexual stages has been well studied, but very little is known about similar phagocytic clearance of mature sexual stages, which are critical for transmission. We evaluated phagocytic uptake of mature sexual (gametocyte) stage parasites by a human monocyte cell line in the absence of immune sera. We found that intact mature stages do not undergo phagocytosis, unless they are either killed or freed from erythrocytes. In view of this observation, we propose that the inability of mature gametocytes to be phagocytized may actually result in malaria transmission advantage. On the other hand, mature gametocytes that are not transmitted to mosquitoes during infection will eventually die and undergo phagocytosis, initiating immune responses that may have transmission blocking potential. A better understanding of early phagocytic clearance and immune responses to gametocytes may identify additional targets for transmission blocking strategies. PMID- 26851168 TI - A facile chemical route for recovery of high quality zinc oxide nanoparticles from spent alkaline batteries. AB - Recycling of spent domestic batteries has gained a great environmental significance. In the present research, we propose a new and simple technique for the recovery of high-purity zinc oxide nanoparticles from the electrode waste of spent alkaline Zn-MnO2 batteries. The electrode material was collected by the manual dismantling and mixed with 5M HCl for reaction with a phosphine oxide reagent Cyanex 923(r) at 250 degrees C for 30min. The desired ZnO nanoparticles were restored from the Zn-Cyanex 923 complex through an ethanolic precipitation step. The recovered particle product with about 5nm diameter exhibited fluorescent properties (emission peak at 400nm) when excited by UV radiation (excitation energy of 300nm). Thus, the proposed technique offered a simple and efficient route for recovering high purity ZnO nanoparticles from spent alkaline batteries. PMID- 26851169 TI - A consumption approach to wastes from economic activities. AB - In a context of waste management policies aimed at promoting waste prevention and recycling and, conversely, reducing waste landfilling, this study investigates how waste is generated and treated in a consumption perspective. A Waste Input Output Analysis is implemented that considers 14 waste fractions and four waste management techniques. Input-Output Tables extended to wastes are initially compiled for the year 2008 considering France and five of its main import suppliers, and further completed with data on waste treatment. Wastes from economic activities are accordingly reallocated to the product categories of household consumption that induce their production. In particular, considering five waste categories (dry recyclable wastes, mixed wastes, mineral wastes, organic wastes, and total wastes) as an aggregation of the 14 waste fractions studied, the ten product categories with the highest contribution account for 64 86% of the total generation of wastes. Waste intensity and volume of expenses are analyzed as the drivers for the amounts of wastes induced by each product category. Similarly, the products responsible for the largest amounts of waste landfilling and incineration without energy recovery, i.e. the management techniques at the bottom of the "waste management hierarchy", are identified. Moreover, this study highlights the relative importance of waste produced abroad as compared to that produced in France, regarding the total amount of waste induced by French household consumption. The sensitivity of results to the modeling of import production is subsequently discussed. Finally, the potential perspectives for this type of consumption approach are considered with respect to its utility and current limitations in a context of waste policy planning, and more particularly regarding the way waste policy targets are set. PMID- 26851170 TI - A modern solid waste management strategy--the generation of new by-products. AB - To benefit the environment and society, EU legislation has introduced a 'zero waste' strategy, in which waste material should be converted to resources. Such legislation is supported by the solid waste hierarchy concept, which is a set of priorities in waste management. Under this concept, municipal solid waste plants (MSWPs) should be equipped with sorting and recycling facilities, composting/incineration units and landfill prisms for residual bulk disposal. However, each of the aforementioned facilities generates by-products that must be treated. This project focuses on the leachates from landfill prisms, including modern prism (MP) that meet EU requirements and previous prism (PP) that provide for the storage of permitted biodegradable waste as well as technological wastewaters from sorting unit (SU) and composting unit (CU), which are usually overlooked. The physico-chemical parameters of the liquid by-products collected over 38 months were supported by quantitative real-time PCR (qPCR) amplifications of functional genes transcripts and a metagenomic approach that describes the archaeal and bacterial community in the MP. The obtained data show that SU and especially CU generate wastewater that is rich in nutrients, organic matter and heavy metals. Through their on-site pre-treatment and recirculation via landfill prisms, the landfill waste decomposition process may be accelerated because of the introduction of organic matter and greenhouse gas emissions may be increased. These results have been confirmed by the progressive abundance of both archaeal community and the methyl coenzyme M reductase (mcrA) gene. The resulting multivariate data set, supported by a principal component analysis, provides useful information for the design, operation and risk assessment of modern MSWPs. PMID- 26851171 TI - Comparison of biodiesel production from sewage sludge obtained from the A2/O and MBR processes by in situ transesterification. AB - The potential of two types of sludge obtained from the anaerobic-anoxic-oxic (A(2)/O) and membrane bioreactor (MBR) processes as lipid feedstock for biodiesel production via in situ transesterification was investigated. Experiments were conducted to determine the optimum conditions for biodiesel yield using three factor and four-level orthogonal and single-factor tests. Several factors, namely, methanol-to-sludge mass ratio, acid concentration, and temperature, were examined. The optimum yield of biodiesel (16.6% with a fatty acid methyl ester purity of 96.7%) from A(2)/O sludge was obtained at a methanol-to-sludge mass ratio of 10:1, a temperature of 60 degrees C, and a H2SO4 concentration of 5% (v/v). Meanwhile, the optimum yield of biodiesel (4.2% with a fatty acid methyl ester purity of 92.7%) from MBR sludge was obtained at a methanol-to-sludge mass ratio of 8:1, a temperature of 50 degrees C, and a H2SO4 concentration of 5% (v/v). In this research, A(2)/O technology with a primary sedimentation tank is more favorable for obtaining energy from wastewater than MBR technology. PMID- 26851172 TI - Constitutive modelling of composite biopolymer networks. AB - The mechanical behaviour of biopolymer networks is to a large extent determined at a microstructural level where the characteristics of individual filaments and the interactions between them determine the response at a macroscopic level. Phenomena such as viscoelasticity and strain-hardening followed by strain softening are observed experimentally in these networks, often due to microstructural changes (such as filament sliding, rupture and cross-link debonding). Further, composite structures can also be formed with vastly different mechanical properties as compared to the individual networks. In this present paper, we present a constitutive model presented in a continuum framework aimed at capturing these effects. Special care is taken to formulate thermodynamically consistent evolution laws for dissipative effects. This model, incorporating possible anisotropic network properties, is based on a strain energy function, split into an isochoric and a volumetric part. Generalisation to three dimensions is performed by numerical integration over the unit sphere. Model predictions indicate that the constitutive model is well able to predict the elastic and viscoelastic response of biological networks, and to an extent also composite structures. PMID- 26851173 TI - Fitness landscapes among many options under social influence. AB - Cultural learning represents a novel problem in that an optimal decision depends not only on intrinsic utility of the decision/behavior but also on transparency of costs and benefits, the degree of social versus individual learning, and the relative popularity of each possible choice in a population. In terms of a fitness-landscape function, this recursive relationship means that multiple equilibria can exist. Here we use discrete-choice theory to construct a fitness landscape function for a bi-axial decision-making map that plots the magnitude of social influence in the learning process against the costs and payoffs of decisions. Specifically, we use econometric and statistical methods to estimate not only the fitness function but also movements along the map axes. To search for these equilibria, we employ a hill-climbing algorithm that leads to the expected values of optimal decisions, which we define as peaks on the fitness landscape. We illustrate how estimation of a measure of transparency, a measure of social influence, and the associated fitness landscape can be accomplished using panel data sets. PMID- 26851174 TI - Oleanane-type triterpene saponins from Hydrocotyle nepalensis. AB - Five new oleanane-type triterpene saponins including steganogenin 3-O-beta-D glucopyranoside (1), steganogenin 3-O-alpha-L-rhamnopyranosyl-(1->2)-beta-D glucopyranoside (2), steganogenin 3-O-beta-D-glucopyranosyl-(1->2)-beta-D glucopyranoside (3), chichipegenin 3-O-alpha-L-rhamnopyranosyl-(1->2)-beta-D glucopyranoside (4) and chichipegenin 3-O-beta-D-glucopyranosyl-(1->2)-beta-D glucopyranoside (5), along with four known oleanane-type triterpenes and triterpene saponins (6-9) were isolated from EtOH extract of the whole plant of Hydrocotyle nepalensis. To the best of our knowledge, oleanane-type triterpenes possessing skeleton with 17, 22-seco-backbone (1-3) are not common in natural products. Compound 8 was isolated as a new natural product. The structures of new compounds were elucidated by extensive spectroscopic methods and chemical evidence. Moreover, the cytotoxic activity of all the isolates against five selected human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) was evaluated and the results indicated that compounds 6 and 7 show stronger cytotoxic activity. PMID- 26851175 TI - Research progress on berberine with a special focus on its oral bioavailability. AB - The natural product berberine (BBR) has become a potential drug in the treatment of diabetes, hyperlipidemia, and cancer. However, the oral delivery of BBR is challenged by its poor bioavailability. It is necessary to improve the oral bioavailability of BBR before it can be used in many clinical applications. Understanding the pharmacokinetic characteristics of BBR will enable the development of suitable formulas that have improved oral bioavailability. The key considerations for BBR are how to enhance the drug absorption and to avoid the intestinal first-pass effect. This review summarizes the pharmacological activities of BBR and analyzes the factors that lead to its poor oral bioavailability. In particular, the therapeutic potential of BBR in new indications from the aspect of oral bioavailability is discussed. In conclusion, BBR is a promising drug candidate for metabolic disorders and cancer but faces considerable challenges due to its poor oral bioavailability. PMID- 26851176 TI - Modulation of WNT/beta-catenin pathway in melanoma by biologically active components derived from plants. AB - Metastatic melanoma is an aggressive cancer, often resistant to treatment. Therefore, it is essential to determine the molecular mechanisms leading to melanoma or underlying resistance to therapy, and the response to targeted inhibition of the RAS/BRAF/MEK/ERK pathway was a good lesson in this respect. Aberrant WNT/beta-catenin pathway is observed in melanoma, and the modulators of this signaling cascade have been under investigation in the context of therapy as well as chemoprevention. Several natural compounds were recognized as being capable of targeting elements of the WNT/beta-catenin pathway in various cancers, however, only a few of them can modulate this pathway in melanoma. This review examines recent research on the role of the WNT/beta-catenin pathway in tumor development and maintenance, as well as summarizes the current knowledge concerning the modulation of this pathway in melanoma by active compounds of natural origin. PMID- 26851177 TI - Evidence of sympatric speciation of elderberry carlaviruses. AB - Five new carlaviruses infecting elderberry were characterized and tentatively named as elderberry virus A-E (ElVA-ElVE). Their genome organization is similar to that of other carlaviruses with size ranging from 8540 to 8628 nucleotides, excluding the polyadenylated tails. ElVA, ElVB and ElVD share a common ancestor as do ElVC and ElVE, indicating that speciation may be sympatric with all viruses having emerged in elderberry. Analyses of the carlavirus conserved domains indicate that the 2-oxoglutarate and Fe(II)-dependent oxygenase motifs are reliable indicators of virus phylogenetic classification with recombination playing a significant role in the evolution of the genus. A universal RT-PCR assay that detects all the elderberry carlaviruses and potentially other members of the genus has been developed. This tool can be used for research and regulatory purposes as elderberry cultivation is rapidly expanding to new areas where the viruses may be absent. PMID- 26851181 TI - Pruning Cancer's Evolutionary Tree with Lesion-Directed Therapy. AB - Next-generation sequencing of spatially and temporally separated biopsies and circulating tumor DNA directs therapy in response to tumor evolution and acquired resistance in colorectal cancer. PMID- 26851182 TI - Adenoid Cystic Carcinoma Can Be Driven by MYB or MYBL1 Rearrangements: New Insights into MYB and Tumor Biology. AB - A majority of adenoid cystic carcinomas (AdCC)-rare tumors of the salivary gland and some other organs-have recently been found to be driven by chromosomal translocations resulting in MYB-NFIB fusions. Brayer and colleagues and Mitani and colleagues have now reported that AdCCs can alternatively be driven by similar rearrangements involving a second MYB family gene, MYBL1, and that these two drivers act in remarkably similar ways. PMID- 26851183 TI - Immunotherapy and Oncogenic Pathways: The PTEN Connection. AB - Peng and colleagues describe the effects of PTEN inactivation on antitumor immunity and response to immune checkpoint blockade in melanoma. These results shed light on the intricate interplay between oncogenic pathways and antitumor immune response. PMID- 26851184 TI - DNA-Guided Precision Medicine for Cancer: A Case of Irrational Exuberance? AB - Precision treatment with targeted cancer drugs requires the selection of patients who are most likely to benefit from a given therapy. We argue here that the use of a combination of both DNA and transcriptome analyses will significantly improve drug response prediction. PMID- 26851185 TI - Epithelial-Mesenchymal Transition Is Associated with a Distinct Tumor Microenvironment Including Elevation of Inflammatory Signals and Multiple Immune Checkpoints in Lung Adenocarcinoma. AB - PURPOSE: Promising results in the treatment of non-small cell lung cancer (NSCLC) have been seen with agents targeting immune checkpoints, such as programmed cell death 1 (PD-1) or programmed death ligand-1 (PD-L1). However, only a select group of patients respond to these interventions. The identification of biomarkers that predict clinical benefit to immune checkpoint blockade is critical to successful clinical translation of these agents. METHODS: We conducted an integrated analysis of three independent large datasets, including The Cancer Genome Atlas of lung adenocarcinoma and two datasets from MD Anderson Cancer Center (Houston, TX), Profiling of Resistance Patterns and Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax (named PROSPECT) and Biomarker-Integrated Approaches of Targeted Therapy for Lung Cancer Elimination (named BATTLE-1). Comprehensive analysis of mRNA gene expression, reverse-phase protein array, IHC, and correlation with clinical data were performed. RESULTS: Epithelial mesenchymal transition (EMT) is highly associated with an inflammatory tumor microenvironment in lung adenocarcinoma, independent of tumor mutational burden. We found immune activation coexistent with elevation of multiple targetable immune checkpoint molecules, including PD-L1, PD-L2, PD-1, TIM-3, B7-H3, BTLA, and CTLA-4, along with increases in tumor infiltration by CD4(+)Foxp3(+) regulatory T cells in lung adenocarcinomas that displayed an EMT phenotype. Furthermore, we identify B7-H3 as a prognostic marker for NSCLC. CONCLUSIONS: The strong association between EMT status and an inflammatory tumor microenvironment with elevation of multiple targetable immune checkpoint molecules warrants further investigation of using EMT as a predictive biomarker for immune checkpoint blockade agents and other immunotherapies in NSCLC and possibly a broad range of other cancers. Clin Cancer Res; 22(14); 3630-42. (c)2016 AACRSee related commentary by Datar and Schalper, p. 3422. PMID- 26851186 TI - STAT3/5-Dependent IL9 Overexpression Contributes to Neoplastic Cell Survival in Mycosis Fungoides. AB - PURPOSE: Sustained inflammation is a key feature of mycosis fungoides (MF), the most common form of cutaneous T-cell lymphoma (CTCL). Resident IL9-producing T cells have been found in skin infections and certain inflammatory skin diseases, but their role in MF is currently unknown. EXPERIMENTAL DESIGN: We analyzed lesional skin from patients with MF for the expression of IL9 and its regulators. To determine which cells were producing IL9, high-throughput sequencing was used to identify malignant clones and Vb-specific antibodies were employed to visualize malignant cells in histologic preparations. To explore the mechanism of IL9 secretion, we knocked down STAT3/5 and IRF4 by siRNA transfection in CTCL cell lines receiving psoralen+UVA (PUVA) +/- anti-IL9 antibody. To further examine the role of IL9 in tumor development, the EL-4 T-cell lymphoma model was used in C57BL/6 mice. RESULTS: Malignant and reactive T cells produce IL9 in lesional skin. Expression of the Th9 transcription factor IRF4 in malignant cells was heterogeneous, whereas reactive T cells expressed it uniformly. PUVA or UVB phototherapy diminished the frequencies of IL9- and IL9r-positive cells, as well as STAT3/5a and IRF4 expression in lesional skin. IL9 production was regulated by STAT3/5 and silencing of STAT5 or blockade of IL9 with neutralizing antibodies potentiated cell death after PUVA treatment in vitro IL9-depleted mice exhibited a reduction of tumor growth, higher frequencies of regulatory T cells, and activated CD4 and CD8 T lymphocytes. CONCLUSIONS: Our results suggest that IL9 and its regulators are promising new targets for therapy development in mycosis fungoides. Clin Cancer Res; 22(13); 3328-39. (c)2016 AACR. PMID- 26851187 TI - A Randomized Phase II/III Study of Naptumomab Estafenatox + IFNalpha versus IFNalpha in Renal Cell Carcinoma: Final Analysis with Baseline Biomarker Subgroup and Trend Analysis. AB - PURPOSE: To prospectively determine the efficacy of naptumomab estafenatox (Nap) + IFNalpha versus IFN in metastatic renal cell carcinoma (RCC). EXPERIMENTAL DESIGN: In a randomized, open-label, multicenter, phase II/III study, 513 patients with RCC received Nap (15 MUg/kg i. v. in three cycles of four once daily injections) + IFN (9 MU s.c. three times weekly), or the same regimen of IFN monotherapy. The primary endpoint was overall survival (OS). RESULTS: This phase II/III study did not meet its primary endpoint. Median OS/PFS for Nap + IFN patients was 17.1/5.8 months versus 17.5/5.8 months for the patients receiving IFN alone (P = 0.56; HR, 1.08/P = 0.41; HR, 0.92). Post hoc exploratory subgroup and trend analysis revealed that the baseline plasma concentrations of anti-SEA/E 120 (anti-Nap antibodies) for drug exposure and IL6 for immune status could be used as predictive biomarkers. A subgroup of patients (SG; n = 130) having concentrations below median of anti-SEA/E-120 and IL6 benefitted greatly from the addition of Nap. In SG, median OS/PFS for the patients treated with Nap + IFN was 63.3/13.7 months versus 31.1/5.8 months for the patients receiving IFN alone (P = 0.02; HR, 0.59/P = 0.02; HR, 0.62). Addition of Nap to IFN showed predicted and transient immune related AEs and the treatment had an acceptable safety profile. CONCLUSIONS: The study did not meet its primary endpoint. Nap + IFN has an acceptable safety profile, and results from post hoc subgroup analyses showed that the treatment might improve OS/PFS in a baseline biomarker-defined RCC patient subgroup. The results warrant further studies with Nap in this subgroup. Clin Cancer Res; 22(13); 3172-81. (c)2016 AACR. PMID- 26851188 TI - Colonoscopic screening shows increased early incidence and progression of adenomas in cystic fibrosis. AB - BACKGROUND: Colorectal cancer is an emerging problem in cystic fibrosis (CF). The goal of this study was to evaluate adenoma detection by systematic colonoscopic screening and surveillance. METHODS: We analyzed prospectively collected results of colonoscopies initiated at age 40years from 88 CF patients at a single Cystic Fibrosis Center. We also reviewed results of diagnostic colonoscopies from 27 patients aged 30-39years performed during the same time period at the Center. RESULTS: The incidence of polyp detection increased markedly after age 40 in CF patients. Greater than 50% were found to have adenomatous polyps; approximately 25% had advanced adenomas as defined by size and/or histopathology; 3% were found to have colon cancer. Multivariate analysis demonstrated specific risk factors for adenoma formation and progression. CONCLUSIONS: Early screening and more frequent surveillance should be considered in patients with CF due to early incidence and progression of adenomas in this patient population. PMID- 26851189 TI - Influence of light source, polarization, education, and training on shade matching quality. AB - STATEMENT OF PROBLEM: Many factors influence the quality of shade selection, and isolating how significantly each of these factors influences results is difficult. PURPOSE: The purpose of this in vitro study was to compare results of shade matching using handheld lights with or without a polarizing filter with results obtained using a professional viewing booth and to analyze the influence of education and training on shade selection outcome. MATERIAL AND METHODS: A total of 96 third-year dental students (evaluators) were randomly separated into 4 groups. Each group was assigned 1 of 2 handheld shade-matching devices (lights) with or without a polarizing filter. Each group performed a shade matching exercise using the handheld light or a professional viewing booth. The exercise consisted of matching shade tabs placed in a typodont to a commercial shade guide. Each group repeated this procedure 4 times over a 9-week period. A lecture on shade matching was presented at the fifth week of the study, between "before" and "after" shade matching procedures. RESULTS: Shade matching scores with handheld lights (7.8) were higher than scores of shade matching with the viewing booth (7.2). The mean scores for before (7.2) and after (7.8) shade matching (with education and training in between) were significantly different. The combined effect of light and education and training improved the shade matching score by 1.2, from 6.8 in the before sessions using the viewing booth to 8.0 in the after sessions using handheld lights. A 21% increase in the number of evaluators who selected 1 of 4 best matches was recorded, 10% for handheld lights versus viewing booth after education and training versus before sessions and 11% between after sessions using handheld lights versus before sessions using viewing booth. CONCLUSIONS: Within the limits of the study, the shade matching scores with handheld lights were significantly better than the results obtained using a viewing booth (P<.01). Using a handheld light with or without a polarizing filter did not influence shade matching results. Mean shade matching scores were significantly better after education and training (P<.01). Light combined with education and training resulted in the greatest increase in shade matching quality. PMID- 26851190 TI - Complexities of Mullerian Anatomy in 46XX Cloacal Exstrophy Patients. AB - STUDY OBJECTIVE: To characterize Mullerian anatomy in 46,XX cloacal exstrophy patients. DESIGN: Retrospective review of prospectively maintained, institutionally approved exstrophy-epispadias-cloacal exstrophy database. SETTING: Tertiary care, high-volume exstrophy center (Division of Pediatric Urology, The Johns Hopkins Hospital, Baltimore, Maryland). PARTICIPANTS: We included 31 patients who were genetically female with cloacal exstrophy for whom records included detailed evaluation of Mullerian anatomy. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Mullerian structures, method of evaluation, management, and sexual activity. RESULTS: Of our patients, 12.9% (3/31) had no identified abnormalities. Vaginal anatomy was described for 30 patients; 3/30 had vaginal agenesis, 14/30 had a single vagina, and 13/30 had vaginal duplication. Of 14 patients with 1 vagina, 5 had atresia/hypoplasia, and 1 had a lateral displacement. One patient with 2 vaginas also had distal atresia. Of the cervices evaluated, 9/14 were duplicated (2/9 with a solitary vagina), and 19/27 of the uteri were duplicated (6/22 with 1 vagina, 1/22 with no vagina). Five patients required imaging to fully characterize their anatomy, and 7 patients had studies that failed to identify Mullerian structures seen in the operating room or on physical examination. Common reconstructive surgeries included vaginoplasties, incisions of vaginal septa, colporrhaphies, and hysterectomies. Sexual activity was confirmed for 3 patients, 2 of whom had conceived. CONCLUSION: Most female cloacal exstrophy patients exhibit abnormalities of the Mullerian system. Axial imaging and ultrasound are helpful diagnostic adjuncts but do not replace careful physical examination and assessment in the operating room. Further studies of sexual activity and fertility are warranted. PMID- 26851192 TI - Distribution and time trends of HIV-1 variants in Poland: Characteristics of non B clades and recombinant viruses. AB - The spread of HIV-1 subtypes varies considerably both worldwide and within Europe, with non-B variants commonly found across various exposure groups. This study aimed to analyse the distribution and temporal trends in HIV-1 subtype variability across Poland. For analysis of the subtype distribution, 1219 partial pol sequences obtained from patients followed up in 9 of 17 Polish HIV treatment centres were used. Subtyping was inferred using the maximum likelihood method; recombination was assessed using the bootscanning and jumping profile hidden Markov model methods. Subtype B dominated in the studied group (n=1059, 86.9%); in 160 (13.1%) sequences, non-B variants were present [A1 (n=63, 5.2%), D (n=43, 3.5%), C (n=22, 1.8%), and F1 (n=2, 0.2%)]. In 25 (2.1%) cases circulating recombinant forms (CRFs) were found. Five A1 variants (0.4%) were unique AB recombinant forms (URF) not previously identified in Poland. Non-B clades were notably more common among females (n=73, 45.6%, p<0.001) and heterosexual individuals (n=103, 66.5%, p<0.001) and less frequent among men who have sex with men (MSM) (n=27, 17.42%, p<0.001). HIV-1 viral load at diagnosis was higher among non-B cases [median: 5.0 (IQR: 4.4-5.6)] vs. [median: 4.8 (IQR: 4.3-5.4) log copies/ml for subtype B (p<0.001)] with a lower CD4(+) lymphocyte count at baseline [median: 248 (IQR: 75-503) for non-B vs. median: 320 (IQR: 125-497) cells/MUl for subtype B; p<0.001]. The frequency of the non-B subtypes proved stable from 2008 (11.5%) to 2014 (8.0%) [OR: 0.95 (95% CI: 0.84-1.07), p=0.4], with no temporal differences for exposure groups, gender, age and AIDS. Despite the predominance of subtype B, the variability of HIV in Poland is notable; both CRFs and URFs are present in the analysed population. Non-B variants are associated with heterosexual transmission, more advanced HIV disease and have stable temporal frequencies. PMID- 26851191 TI - Changes in Physical Activity Following a Genetic-Based Internet-Delivered Personalized Intervention: Randomized Controlled Trial (Food4Me). AB - BACKGROUND: There is evidence that physical activity (PA) can attenuate the influence of the fat mass- and obesity-associated (FTO) genotype on the risk to develop obesity. However, whether providing personalized information on FTO genotype leads to changes in PA is unknown. OBJECTIVE: The purpose of this study was to determine if disclosing FTO risk had an impact on change in PA following a 6-month intervention. METHODS: The single nucleotide polymorphism (SNP) rs9939609 in the FTO gene was genotyped in 1279 participants of the Food4Me study, a four arm, Web-based randomized controlled trial (RCT) in 7 European countries on the effects of personalized advice on nutrition and PA. PA was measured objectively using a TracmorD accelerometer and was self-reported using the Baecke questionnaire at baseline and 6 months. Differences in baseline PA variables between risk (AA and AT genotypes) and nonrisk (TT genotype) carriers were tested using multiple linear regression. Impact of FTO risk disclosure on PA change at 6 months was assessed among participants with inadequate PA, by including an interaction term in the model: disclosure (yes/no) * FTO risk (yes/no). RESULTS: At baseline, data on PA were available for 874 and 405 participants with the risk and nonrisk FTO genotypes, respectively. There were no significant differences in objectively measured or self-reported baseline PA between risk and nonrisk carriers. A total of 807 (72.05%) of the participants out of 1120 in the personalized groups were encouraged to increase PA at baseline. Knowledge of FTO risk had no impact on PA in either risk or nonrisk carriers after the 6-month intervention. Attrition was higher in nonrisk participants for whom genotype was disclosed (P=.01) compared with their at-risk counterparts. CONCLUSIONS: No association between baseline PA and FTO risk genotype was observed. There was no added benefit of disclosing FTO risk on changes in PA in this personalized intervention. Further RCT studies are warranted to confirm whether disclosure of nonrisk genetic test results has adverse effects on engagement in behavior change. TRIAL REGISTRATION: ClinicalTrials.gov NCT01530139; http://clinicaltrials.gov/show/NCT01530139 (Archived by WebCite at: http://www.webcitation.org/6XII1QwHz). PMID- 26851193 TI - Application of immuno-PCR for the detection of early stage cancer. AB - Cancer detection in premalignant stage is directly related with increase survival rate. Several biomarkers have been investigated and characterized for monitoring changes inside the cancerous cells. Although enzyme-linked immunosorbent assay (ELISA) is the method of choice in clinical practice for detecting biomarkers in serum/urine samples. However, in certain malignancies the amount of biomarkers before reaching metastasis are too low to be detected by conventional ELISA. The seminal work of Sano et al. led to the development of highly sensitive and powerful detection method, the immuno-PCR (iPCR), which can detect very small amount of antigens/biomarkers. In spite of, several publications on iPCR sensitivity, it has not been recommended for clinical use and is limited to the scientific community only. In order to evaluate the importance of iPCR, we have made an effort to collect published studies, supporting the use of iPCR in detecting premalignant cancer. PMID- 26851194 TI - Superficial mucoceles at surgical mucosal margins of excised oral cancer specimens: An unexpected finding. PMID- 26851195 TI - Culture positivity and bacterial burden thresholds for Legionella in hospital water: Proceed with caution. PMID- 26851197 TI - Reply to Dikon in response to "A response to the relationship between different types of sharps containers and Clostridium difficile infection rates in acute care hospitals". PMID- 26851196 TI - The influence of biofilm formation and multidrug resistance on environmental survival of clinical and environmental isolates of Acinetobacter baumannii. AB - BACKGROUND: Acinetobacter baumannii is a gram-negative, opportunistic pathogen. Its ability to form biofilm and increasing resistance to antibiotic agents present challenges for infection control. A better understanding of the influence of biofilm formation and antibiotic resistance on environmental persistence of A baumannii in hospital settings is needed for more effective infection control. METHODS: A baumannii strains isolated from patients and the hospital environment were identified via Matrix Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) mass spectrometry (Bruker Daltonics, Bellerica, MA), repetitive extragenic palindromic polymerase chain reaction genotyped, and antibiotic resistance was determined using Vitek 2 (bioMerieux, Inc, Durham NC). Biofilm mass was quantified via microtiter plate method and desiccation tolerance determined up to 56 days. RESULTS: High biofilm forming, clinical, multidrug resistant- (MDR) positive strains were 50% less likely to die of desiccation than low biofilm, non-MDR strains. In contrast, environmental, MDR-positive, low biofilm forming strains had a 2.7 times increase in risk of cell death due to desiccation compared with their MDR-negative counterparts. MDR-negative, high biofilm forming environmental strains had a 60% decrease in risk compared with their low biofilm forming counterparts. CONCLUSION: The MDR-positive phenotype was deleterious for environmental strains and the high biofilm phenotype was critical for survival. This study provides evidence of the trade-off between antibiotic resistance and desiccation tolerance, driven by condition-dependent adaptation, and establishes rationale for research into the genetic basis of the variation in fitness cost between clinical and environmental isolates. PMID- 26851198 TI - Chronic graft versus host disease as a weapon for treating chronic myelomonocytic leukemia. PMID- 26851199 TI - The Saint Louis University Mental Status Examination Is Better than the Mini Mental State Examination to Determine the Cognitive Impairment in Turkish Elderly People. AB - INTRODUCTION: Presence of detailed screening instruments to detect cognitive impairment in the older adults' culture and language is very essential. The Saint Louis University Mental Status Examination (SLUMS) is one of cognitive screening scales used. The aim of the study was to establish the validity and reliability of the Turkish version of SLUMS (SLUMS-T). METHODS: Two hundred seventy-four participants aged 60 years and older admitted to our geriatric clinic were screened for cognitive impairment using SLUMS-T and Mini-Mental State Examination. Internal consistency was analyzed with Cronbach alpha test. Area under curves of receiver operating characteristic analyses were used to test the predictive accuracy of the SLUMS-T for detecting amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD) to set an appropriate cut-off point. RESULTS: The SLUMS-T scores were positively correlated with the Mini-Mental State Examination scores of the patients with aMCI and patients with AD and controls (r = 0.687, P < .001; r = 0.880, P < .001; respectively). Internal consistency of the SLUMS-T was Cronbach alpha = 0.85. It was found that SLUMS-T with a cut-off point of 23 had a sensitivity of 66.6% and a specificity of 72.3% for the diagnosis of aMCI, and with a cut-off point of 20 had a sensitivity of 83.8% and a specificity of 87.3% for the diagnosis of AD. CONCLUSIONS: SLUMS-T was demonstrated to have sufficient validity and reliability to evaluate cognitive impairment including MCI among Turkish elderly people. PMID- 26851200 TI - Modulation of nucleus accumbens connectivity by alcohol drinking and naltrexone in alcohol-preferring rats: A manganese-enhanced magnetic resonance imaging study. AB - The nonselective opioid receptor antagonist naltrexone is now used for the treatment of alcoholism, yet naltrexone's central mechanism of action remains poorly understood. One line of evidence suggests that opioid antagonists regulate alcohol drinking through interaction with the mesolimbic dopamine system. Hence, our goal here was to examine the role of the nucleus accumbens connectivity in alcohol reinforcement and naltrexone's actions using manganese-enhanced magnetic resonance imaging (MEMRI). Following long-term free-choice drinking of alcohol and water, AA (Alko Alcohol) rats received injections of MnCl2 into the nucleus accumbens for activity-dependent tracing of accumbal connections. Immediately after the accumbal injections, rats were imaged using MEMRI, and then allowed to drink either alcohol or water for the next 24h. Naltrexone was administered prior to the active dark period, and the second MEMRI was performed 24h after the first scan. Comparison of signal intensity at 1 and 24h after accumbal MnCl2 injections revealed an ipsilateral continuum through the ventral pallidum, bed nucleus of the stria terminalis, globus pallidus, and lateral hypothalamus to the substantia nigra and ventral tegmental area. Activation was also seen in the rostral part of the insular cortex and regions of the prefrontal cortex. Alcohol drinking resulted in enhanced activation of these connections, whereas naltrexone suppressed alcohol-induced activity. These data support the involvement of the accumbal connections in alcohol reinforcement and mediation of naltrexone's suppressive effects on alcohol drinking through their deactivation. PMID- 26851202 TI - Concordance Between Iothalamate and Iohexol Plasma Clearance. PMID- 26851201 TI - Rotigotine in Hemodialysis-Associated Restless Legs Syndrome: A Randomized Controlled Trial. AB - BACKGROUND: Restless legs syndrome (RLS) has been associated with insomnia, decreased quality of life, and increased morbidity and mortality in end-stage renal disease. This randomized controlled trial investigated effects of rotigotine in patients with RLS and end-stage renal disease. STUDY DESIGN: Double blind placebo-controlled study. SETTING & PARTICIPANTS: Adults with moderate to severe RLS (International RLS Study Group Rating Scale [IRLS] >= 15) and Periodic Limb Movement Index (PLMI) >= 15 who were receiving thrice-weekly hemodialysis enrolled from sites in the United States and Europe. INTERVENTION: Following randomization and titration (<=21 + 3 days) to optimal-dose rotigotine (1-3mg/24 h) or placebo, patients entered a 2-week maintenance period. Polysomnography was performed at baseline and the end of maintenance. OUTCOMES & MEASUREMENTS: Primary efficacy outcome: reduction in PLMI, assessed by ratio of PLMI at end of maintenance to baseline. Secondary/other outcomes (P values exploratory) included mean changes from baseline in PLMI, IRLS, and Clinical Global Impression item 1 (CGI-1 [severity of illness]) score. RESULTS: 30 patients were randomly assigned (rotigotine, 20; placebo, 10); 25 (15; 10) completed the study with evaluable data. Mean (SD) PLMI ratio (end of maintenance to baseline) was 0.7+/-0.4 for rotigotine and 1.3+/-0.7 for placebo (analysis of covariance treatment ratio, 0.44; 95% CI, 0.22 to 0.88; P=0.02). Numerical improvements were observed with rotigotine versus placebo in IRLS and CGI-1 (least squares mean treatment differences of -6.08 [95% CI, -12.18 to 0.02; P=0.05] and -0.81 [95% CI, -1.94 to 0.33; P=0.2]). 10 of 15 rotigotine and 2 of 10 placebo patients were CGI-1 responders (>=50% improvement). Hemodialysis did not affect unconjugated rotigotine concentrations. The most common adverse events (>=2 patients) were nausea (rotigotine, 4 [20%]; placebo, 0); vomiting (3 [15%]; 0); diarrhea (1 [5%]; 2 [20%]); headache (2 [10%]; 0); dyspnea (2 [10%]; 0); and hypertension (2 [10%]; 0). LIMITATIONS: Small sample size and short duration. CONCLUSIONS: Rotigotine improved periodic limb movements and RLS symptoms in the short term among ESRD patients requiring hemodialysis in a small-scale study. No dose adjustments are necessary for hemodialysis patients. PMID- 26851203 TI - Development and performance evaluation of novel nanoparticles of a grafted copolymer loaded with curcumin. AB - Inflammatory bowel disease (IBD) is an inflammatory condition with mucosal ulceration, edema and hemorrhage of gastrointestinal tract. Curcumin has been shown to mitigate colitis in animal models. However, its usefulness is reduced due to poor pharmacokinetic behavior and low oral bioavailability. To address this, novel pH-sensitive hydrolyzed polyacrylamide-grafted-xanthan gum (PAAm-g XG) nanoparticles (NPs) loaded with curcumin were prepared for colonic delivery. Optimized nanoparticles (CN20) were spherical, with an average size of 425 nm. A negligible amount of curcumin (~8%) was released from CN20 NPs in pH 1.2 and 4.5 solutions. When the pH was increased to 7.2, curcumin release was comparatively faster than that observed with pH 1.2 and 4.5 collectively. In pH 6.8 solution, excellent release of curcumin was observed. Highest curcumin release was observed when rat caecal contents were incorporated in pH 6.8 solution, indicating microflora-dependent drug release property of NPs. In acetic acid-induced IBD in rats, curcumin NPs reduced myeloperoxidase and nitrite levels, prevented weight loss and attenuated colonic inflammation. Curcumin was better absorbed systemically in nanoparticulate form with increased Cmax (~3 fold) and AUC (~2.5 fold) than when delivered as free curcumin. We demonstrate successful development of grafted co-polymeric NPs containing drug suitable for colon targeting. PMID- 26851204 TI - Characterization of microcapsulated beta-carotene formed by complex coacervation using casein and gum tragacanth. AB - Complex coacervation in casein/gum tragacanth (CAS/GT) mixtures was studied as a function of pH, initial protein to polysaccharide mixing ratio (Pr:Ps), total biopolymer concentration, core material load and ionic strength. This study is aimed at understanding how these parameters influence the coacervation kinetics, the coacervate yield, and entrapment efficiency. At a Pr:Ps=2:1, an optimum pH of complex coacervation was found 4.35, at which the intensity of electrostatic interaction was maximum. At these conditions, the phase separation occurred the fastest and the final coacervate yield and entrapment efficiency were the largest. Moreover, the developed beta-carotene loaded microcapsules formulation was found to have particle size 159.71+/-2.16MUm, coacervates yield 82.51+/ 0.412%, entrapment efficiency 79.36+/-0.541%. Varying the Pr:Ps shifted the value of optimum pH. Electrostatic interaction and formation of coacervates was confirmed by Fourier Transform Infra Red (FTIR) spectra. Size and surface properties of coacervates were studied using Scanning Electron Microscopy (SEM). Entrapment of core material within the coacervates was confirmed by Confocal Laser Scanning Microscope (CLSM). The resultant formulation was evaluated for release study and antioxidant activity. Stability of encapsulated beta-carotene was evaluated under three levels of temperature (5, 25 and 40 degrees C) for 3 months. Encapsulation strongly increased the stability of micronutrients. Our results advocate potential of microcapsules as a novel carrier for the safeguard and sustained release of micronutrient. PMID- 26851205 TI - Mycobacterium tuberculosis PE9 protein has high activity binding peptides which inhibit target cell invasion. AB - PE/PPE proteins are involved in several processes during Mycobacterium tuberculosis (Mtb) infection of target cells; studying them is extremely interesting as they are the only ones from the Mycobacterium genus, they abound in pathogenic species such as Mtb and their function remains yet unknown. The PE9 protein (Rv1088) was characterised, the rv1088 gene was identified by PCR in Mtb complex strains and its expression and localisation on mycobacterial surface was confirmed by Western blot and immunoelectron microscopy. Bioinformatics tools were used for predicting PE9 protein structural aspects and experimental study involved the circular dichroism of synthetic peptides. The peptides were tested in binding assays involving U937 and A549 cells; two high activity binding peptides (HABPs) were found for both cell lines (39226 (1)MSYMIATPAALTAAATDIDGI(21) and 39232-(125)YQRHFGTGGQPEFRQHSEHRR(144)), one for U937 (39231-(104)YAGAGRRQRRRRSGDGQWRLRQ(124)) and one for A549 (39230 (83)YGTGVFRRRRGRQTVTAAEHRA(103)). HABP 39232 inhibited mycobacterial entry to A549 cells (~70%) and U937 cells (~50%), peptides 39226 and 39231 inhibited entry to U937 cells (~60% and 80%, respectively) and peptide 39230 inhibited entry to A549 cells (~60%). This emphasised HABPs' functional importance in recognition between Mtb H37Rv and target cell receptors. These peptide sequences could be involved in invasion and were recognised by the host's immune system, thereby highlighting their use when designing an efficient anti-tuberculosis multiantigenic vaccine. PMID- 26851206 TI - New core-shell hyperbranched chitosan-based nanoparticles as optical sensor for ammonia detection. AB - In this paper, preparation of new core-shell amino-terminated hyperbranched chitosan nanoparticles (HBCs-NH2) NPs is described. The synthesized nanoparticles were characterized using ninhydrin assay, FTIR, TGA, and FESEM. The newly prepared (HBCs-NH2) NPs were then used as a platform for facile and controlled synthesis of silver nanoparticles (AgNPs) which was confirmed using FTIR, UV-vis spectrometry, X-ray diffraction, SEM and HRTEM. Formation of the AgNPs was also noted upon changing the color of (HBCs-NH2) NPs suspension from colorless into yellow as well as through the appearance of surface plasmon resonance (SPR) peak at 400 nm. HRTEM showed a uniform and spherical morphology of the resulting HBCs NH2 NPs with average size 400 nm, and the AgNPs were formed mainly on their surface with average size of 20-50 nm. The newly developed (HBCs-NH2) NPs-AgNPs showed a great potential as optical sensor for efficient detection of the ammonia concentration in solutions based on the change in the SPR. PMID- 26851207 TI - Optimization and characterization of PHA from isolate Pannonibacter phragmitetus ERC8 using glycerol waste. AB - Polyhydroxyalkanoates (PHAs) have been considered as a good alternative for petrochemical based polymers due to its biodegradability. However, a high production cost limits their acceptance in industries. In present work, efforts have been made to optimize the production of PHA by Pannonibacter phragmitetus ERC8 using glycerol waste as a sole carbon source, with enhanced polymer production in a cost effective way. To check the possibility of growth and polymer accumulation potential of P. phragmitetus ERC8, various low cost substrates such as food waste, mutton tallow, whey, sugarcane bagasse, corn steep liquor and glycerol waste were used. Optimum concentration of selected factors obtained as response of statistical experimental design were 0.8% (v/v) glycerol waste, 0.26% (w/v) BHM and 1.25%OD as an inoculum for the maximum PHA production. The suggested model was validated and maximum 1.36 g/L of PHA production was obtained after 96 h. PHA production of 1.87 g/L was achieved in 5L (working volume 3 L) lab scale bioreactor with the suggested media components by RSM (Response Surface Methodology). Characterization of the PHA by NMR spectroscopy revealed that the polymer was a hetromonomer of (R)-3-hydroxybutyrate and medium chain length 3HA[(R)-3-hydroxyalkanoate] monomers. PMID- 26851208 TI - Safety and biocompatibility of graphene: A new generation nanomaterial for biomedical application. AB - Graphene, a material with great application potential is expected to revolutionize various fields in the near future particularly biomedical field with its inherent properties. However, significant increase in the research on graphene in the recent years has created anxiety about their safety/biocompatibility towards living organisms. Though there is increase in reports on graphene synthesis and application, in parallel reports on unwanted toxic effects of these materials is under scrutiny. Before exploiting their use, any engineered nanomaterials should undergo through investigation regarding the risk and health hazards imposed by them. Toxicity of nanomaterial depends on many factors like size, shape, surface chemistry, dose, duration and the biological milieu. In this account, we reviewed physico-chemical properties of graphene that plays a key role in toxicity prediction. We also detailed some examples of the in vitro and in vivo toxicity studies that have been published so far. The potential environmental risk associated with these carbon materials is also addressed, in order to avoid unintentional leaching of these materials into surface water. PMID- 26851209 TI - Balloon-Occlusion Catheter Onyx Embolization of a Spinal Dural Arteriovenous Fistula Presenting with Subarachnoid Hemorrhage in a Pediatric Patient. AB - OBJECTIVE: Spinal dural arteriovenous fistulas (DAVFs) are insidious pathologies that, if left untreated, harbor potentially devastating consequences to the central nervous system. Spinal DAVFs are rare in the adult population and exceedingly uncommon in the pediatric population. In this report, we describe a spinal DAVF in a 3-year-old child whose initial presentation is subarachnoid hemorrhage (SAH). Balloon-test occlusion and balloon-catheter-assisted embolization of DAVF have not been previously described, and their advantages over alternative embolic and surgical techniques are discussed. METHODS: We performed a literature search on MEDLINE/PubMed to review current reports describing the epidemiology, clinical presentation, and treatment of spinal DAVFs. In this report, we describe a spinal DAVF in a 3-year-old child whose initial presentation is SAH. RESULTS: A spinal DAVF was diagnosed after deciding to image not only the brain but also the spine. Using a balloon-occlusion catheter, we confirmed that the DAVF arterial feeding vessel could be safely embolized. We then proceeded to effectively treat the DAVF with balloon-catheter assisted Onyx-18 embolization. CONCLUSION: Based on our report and an analysis of the literature, we propose that pediatric patients presenting with nontraumatic SAH should undergo at least a magnetic resonance imaging of the brain and cervical spine as part of their initial workup. In addition, we describe a balloon-occlusion catheter embolization technique that allows not only excellent embolic penetration of the fistula but also prevention of microcatheter reflux and lessening of the need for a tedious plug-and-stack technique. PMID- 26851210 TI - Optimal Peak Systolic Velocity Thresholds for Predicting Internal Carotid Artery Stenosis Greater than or Equal to 50%, 60%, 70%, and 80%. AB - BACKGROUND: We aimed to determine the optimal peak systolic velocity (PSV) thresholds for predicting >=50%, >=60%, >=70%, and >=80% internal carotid artery (ICA) stenosis. METHODS: Patients who underwent both carotid ultrasonography and cerebral angiography during hospitalization were consecutively and retrospectively enrolled. The degree of ICA stenosis was calculated using the North American Symptomatic Carotid Endarterectomy Trial method on cerebral angiography. The optimal PSV thresholds for predicting >=50%, >=60%, >=70%, and >=80% ICA stenosis were determined using receiver operating characteristic curves and the Youden index. RESULTS: A total of 127 ICAs were analyzed. The optimal PSV thresholds for predicting >=50%, >=60%, >=70%, and >=80% ICA stenosis were 130 cm/s (sensitivity, 95%; specificity, 85%; positive predictive value [PPV], 75%; negative predictive value [NPV], 97%; overall accuracy, 88%), 160 cm/s (sensitivity, 91%; specificity, 94%; PPV, 83%; NPV, 97%; overall accuracy, 93%), 200 cm/s (sensitivity, 96%; specificity, 95%; PPV, 83%; NPV, 99%; overall accuracy, 95%), and 270 cm/s (sensitivity, 89%; specificity, 94%; PPV, 74%; NPV, 98%; overall accuracy, 94%), respectively. CONCLUSIONS: The optimal PSV thresholds for predicting >=50%, >=60%, >=70%, and >=80% ICA stenosis were 130 cm/s, 160 cm/s, 200 cm/s, and 270 cm/s, respectively. All of them had high diagnostic accuracies. PMID- 26851212 TI - Inter-rater Agreement in Three Perfusion-Computed Tomography Evaluation Methods before Endovascular Therapy for Acute Ischemic Stroke. AB - PURPOSE: There is ongoing debate on which method of perfusion computed tomography (PCT) evaluation in ischemic stroke is the most appropriate for improved selection of patients for endovascular treatment. We sought to test different assessment methods for inter-rater reliability. METHODS: Twenty-six patients were enrolled prospectively before endovascular therapy for acute anterior circulation ischemic stroke. Three raters experienced in stroke imaging and blinded to other imaging and clinical information independently analyzed 22 technically successful PCT scans according to 3 prespecified assessment methods applied to cerebral blood flow (CBF)/cerebral blood volume (CBV) and time-to-peak (TTP) maps: (1) visual mismatch estimate (VME), (2) Alberta Stroke Program Early CT Score perfusion method (ASPECTS-PCT), and (3) quantitative perfusion ratios (qPRs): RCBF, RCBV, RTTP. Inter-rater agreement was assessed with Cohen's kappa, intraclass correlation coefficients (ICC), Bland-Altman plots, and global and descriptive statistics. RESULTS: Significant differences between raters were found with VME and ASPECTS-PCT (P < .001) but with qPRs only for CBV (P = .03). Inter-rater agreement for VME was at best moderate by kappa statistics (.51); moderate by ICC for all parametric maps of ASPECTS-PCT (.56-.62), strong for RTTP (.76), and excellent for RCBF (.92) and RCBV (.86). Pairwise comparisons revealed less scattering of individual values with qPRs and less deviation of mean differences from 0, suggesting minor systematic deviation by any 1 rater as compared with VME or ASPECTS-PCT. CONCLUSION: PCT evaluation methods used before endovascular therapy for acute anterior circulation stroke are subject to substantial inter-rater disagreement. QPRs in PCT evaluation had better inter rater reliability than the often used VME and ASPECTS-PCT assessment. PMID- 26851211 TI - Challenges in Recruitment for the Study of Noninvasive Brain Stimulation in Stroke: Lessons from Deep Brain Stimulation. AB - OBJECTIVE: Noninvasive brain stimulation (NIBS) can augment functional recovery following stroke; however, the technique lacks regulatory approval. Low enrollment in NIBS clinical trials is a key roadblock. Here, we pursued evidence to support the prevailing opinion that enrollment in trials of NIBS is even lower than enrollment in trials of invasive, deep brain stimulation (DBS). METHODS: We compared 2 clinical trials in stroke conducted within a single urban hospital system, one employing NIBS and the other using DBS, (1) to identify specific criteria that generate low enrollment rates for NIBS and (2) to devise strategies to increase recruitment with guidance from DBS. RESULTS: Notably, we found that enrollment in the NIBS case study was 5 times lower (2.8%) than the DBS trial (14.5%) (chi(2) = 20.815, P < .0001). Although the number of candidates who met the inclusion criteria was not different (chi(2) = .04, P < .841), exclusion rates differed significantly between the 2 studies (chi(2) = 21.354, P < .0001). Beyond lack of interest, higher exclusion rates in the NIBS study were largely due to exclusion criteria that were not present in the DBS study, including restrictions for recurrent strokes, seizures, and medications. CONCLUSIONS: Based on our findings, we conclude and suggest that by (1) establishing criteria specific to each NIBS modality, (2) adjusting exclusion criteria based on guidance from DBS, and (3) including patients with common contraindications based on a probability of risk, we may increase enrollment and hence significantly impact the feasibility and generalizability of NIBS paradigms, particularly in stroke. PMID- 26851213 TI - A role for tuned levels of nucleosome remodeler subunit ACF1 during Drosophila oogenesis. AB - The Chromatin Accessibility Complex (CHRAC) consists of the ATPase ISWI, the large ACF1 subunit and a pair of small histone-like proteins, CHRAC-14/16. CHRAC is a prototypical nucleosome sliding factor that mobilizes nucleosomes to improve the regularity and integrity of the chromatin fiber. This may facilitate the formation of repressive chromatin. Expression of the signature subunit ACF1 is restricted during embryonic development, but remains high in primordial germ cells. Therefore, we explored roles for ACF1 during Drosophila oogenesis. ACF1 is expressed in somatic and germline cells, with notable enrichment in germline stem cells and oocytes. The asymmetrical localization of ACF1 to these cells depends on the transport of the Acf1 mRNA by the Bicaudal-D/Egalitarian complex. Loss of ACF1 function in the novel Acf1(7) allele leads to defective egg chambers and their elimination through apoptosis. In addition, we find a variety of unusual 16 cell cyst packaging phenotypes in the previously known Acf1(1) allele, with a striking prevalence of egg chambers with two functional oocytes at opposite poles. Surprisingly, we found that the Acf1(1) deletion--despite disruption of the Acf1 reading frame--expresses low levels of a PHD-bromodomain module from the C-terminus of ACF1 that becomes enriched in oocytes. Expression of this module from the Acf1 genomic locus leads to packaging defects in the absence of functional ACF1, suggesting competitive interactions with unknown target molecules. Remarkably, a two-fold overexpression of CHRAC (ACF1 and CHRAC-16) leads to increased apoptosis and packaging defects. Evidently, finely tuned CHRAC levels are required for proper oogenesis. PMID- 26851214 TI - UHRF1 regulation of Dnmt1 is required for pre-gastrula zebrafish development. AB - Landmark epigenetic events underlie early embryonic development, yet how epigenetic modifiers are regulated to achieve rapid epigenome re-patterning is not known. Uhrf1 and DNA methyltransferase 1 (Dnmt1) are known to largely mediate maintenance DNA methylation and Uhrf1 is also required for both Dnmt1 localization and stability. Here, we investigate how these two key epigenetic modifiers regulate early zebrafish development and characterize the developmental consequences of disrupting their homeostatic relationship. Unlike Uhrf1 knockdown, which causes developmental arrest and death prior to gastrulation, overexpression of human UHRF1 (WT-UHRF1) caused asymmetric epiboly, inefficient gastrulation and multi-systemic defects. UHRF1 phosphorylation was previously demonstrated as essential for zebrafish embryogenesis, and we found that penetrance of the asymmetric epiboly phenotype was significantly increased in embryos injected with mRNA encoding non-phosphorylatable UHRF1 (UHRF1(S661A)). Surprisingly, both WT-UHRF1 and UHRF1(S661A) overexpression caused DNA hypomethylation. However, since other approaches that caused an equivalent degree of DNA hypomethylation did not cause the asymmetric epiboly phenotype, we conclude that bulk DNA methylation is not the primary mechanism. Instead, UHRF1(S661A) overexpression resulted in accumulation of Dnmt1 protein and the overexpression of both WT and a catalytically inactive Dnmt1 phenocopied the assymetric epiboly phenotype. Dnmt1 knockdown suppressed the phenotype caused by UHRF1(S661A) overexpression, and Uhrf1 knockdown suppressed the effect of Dnmt1 overexpression. Therefore, we conclude that the interaction between these two proteins is the mechanism underlying the gastrulation defects. This indicates that Dnmt1 stability requires UHRF1 phosphorylation and that crosstalk between the proteins is essential for the function of these two important epigenetic regulators during gastrulation. PMID- 26851217 TI - NK Cell Proportion and Number Are Influenced by Genetic Loci on Chromosomes 8, 9, and 17. AB - NK cells play a crucial role in innate immunity due to their direct cytotoxicity toward tumors, virally infected cells, and stressed cells, and they also contribute to the orchestration of the adaptive response by their ability to produce immunoregulatory cytokines. In secondary lymphoid organs, NK cells compose the third most abundant lymphocyte subset after T cells and B cells. In this study, we perform an unbiased linkage analysis to determine the genetic loci that may limit the size of the NK cell compartment. Specifically, we exploit differences in NK cell proportion and absolute number between the C57BL/6 and the NOD mice. In addition to the previously identified linkage to chromosome 8, we find that a locus on chromosome 17, which encompasses the MHC locus, impacts NK cell number. Moreover, we identify a locus on mouse chromosome 9 that is strongly linked to the proportion and absolute number of NK cells. Using NOD congenic mice, we validate that both the MHC and the chromosome 9 loci influence the proportion and absolute number of NK cells. We have thus identified additional loci specifically linked to the proportion of NK cells and present some of the potential candidate genes comprised within these loci. PMID- 26851215 TI - Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-kappaB Transcription Factors RELB and NF-kappaB2 in B Cells. AB - BAFF is critical for the survival and maturation of mature B cells. BAFF, via BAFFR, activates multiple signaling pathways in B cells, including the alternative NF-kappaB pathway. The transcription factors RELB and NF-kappaB2 (p100/p52) are the downstream mediators of the alternative pathway; however, the B cell-intrinsic functions of these NF-kappaB subunits have not been studied in vivo using conditional alleles, either individually or in combination. We in this study report that B cell-specific deletion of relb led to only a slight decrease in the fraction of mature splenic B cells, whereas deletion of nfkb2 caused a marked reduction. This phenotype was further exacerbated upon combined deletion of relb and nfkb2 and most dramatically affected the maintenance of marginal zone B cells. BAFF stimulation, in contrast to CD40 activation, was unable to rescue relb/nfkb2-deleted B cells in vitro. RNA-sequencing analysis of BAFF-stimulated nfkb2-deleted versus normal B cells suggests that the alternative NF-kappaB pathway, in addition to its critical role in BAFF-mediated cell survival, may control the expression of genes involved in the positioning of B cells within the lymphoid microenvironment and in the establishment of T cell-B cell interactions. Thus, by ablating the downstream transcription factors of the alternative NF kappaB pathway specifically in B cells, we identify in this study a critical role for the combined activity of the RELB and NF-kappaB2 subunits in B cell homeostasis that cannot be compensated for by the canonical NF-kappaB pathway under physiological conditions. PMID- 26851216 TI - Cutting Edge: NFAT Transcription Factors Promote the Generation of Follicular Helper T Cells in Response to Acute Viral Infection. AB - Follicular CD4(+) Th (Tfh) cells provide B cell help in germinal center reactions that support class switching, somatic hypermutation, and the generation of high affinity Abs. In this article, we show that deficiency in NFAT1 and NFAT2 in CD4(+) T cells leads to impaired germinal center reactions upon viral infection because of reduced Tfh cell differentiation and defective expression of proteins involved in T/B interactions and B cell help, including ICOS, PD-1, and SLAM family receptors. Genome-wide chromatin immunoprecipitation data suggest that NFAT proteins likely directly participate in regulation of genes important for Tfh cell differentiation and function. NFAT proteins are important TCR and Ca(2+) dependent regulators of T cell biology, and in this article we demonstrate a major positive role of NFAT family members in Tfh differentiation. PMID- 26851218 TI - NK Cell Maturation and Cytotoxicity Are Controlled by the Intramembrane Aspartyl Protease SPPL3. AB - NK cell maturation is critical for normal effector function and the innate immune response to tumors and pathogens. However, the molecular pathways that control NK cell maturation remain largely undefined. In this article, we investigate the role of SPPL3, an intramembrane aspartyl protease, in murine NK cell biology. We find that deletion of SPPL3 in the hematopoietic system reduces numbers of peripheral NK cells, clearance of MHC class I-deficient tumors in vivo, and cytotoxicity against tumor cells in vitro. This phenotype is concomitant with reduced numbers of CD27(+)CD11b(+) and CD27(-)CD11b(+) NK cells, indicating a requirement for SPPL3 in efficient NK cell maturation. NK cell-specific deletion of SPPL3 results in the same deficiencies, revealing a cell-autonomous role for SPPL3 in these processes. CRISPR/Cas9 genomic editing in murine zygotes was used to generate knockin mice with a catalytically compromised SPPL3 D271A allele. Mice engineered to express only SPPL3 D271A in NK cells phenocopy mice deleted for SPPL3, indicating a requirement for SPPL3 protease activity in NK cell biology. Our results identify SPPL3 as a cell-autonomous molecular determinant of NK cell maturation and expand the role of intramembrane aspartyl proteases in innate immunity. PMID- 26851220 TI - Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice. AB - Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of alpha4beta7(-) and alpha4beta7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. PMID- 26851219 TI - IL-10+ Innate-like B Cells Are Part of the Skin Immune System and Require alpha4beta1 Integrin To Migrate between the Peritoneum and Inflamed Skin. AB - The skin is an important barrier organ and frequent target of autoimmunity and allergy. In this study, we found innate-like B cells that expressed the anti inflammatory cytokine IL-10 in the skin of humans and mice. Unexpectedly, innate like B1 and conventional B2 cells showed differential homing capacities with peritoneal B1 cells preferentially migrating into the inflamed skin of mice. Importantly, the skin-homing B1 cells included IL-10-secreting cells. B1 cell homing into the skin was independent of typical skin-homing trafficking receptors and instead required alpha4beta1-integrin. Moreover, B1 cells constitutively expressed activated beta1 integrin and relocated from the peritoneum to the inflamed skin and intestine upon innate stimulation, indicating an inherent propensity to extravasate into inflamed and barrier sites. We conclude that innate-like B cells migrate from central reservoirs into skin, adding an important cell type with regulatory and protective functions to the skin immune system. PMID- 26851221 TI - Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence. AB - Dendritic cells (DCs) are specifically equipped with the G protein-coupled receptor 34 (GPR34). Tight regulation of GPR34 gene expression seems highly important for proper immunological functions, because the absence of this receptor leads to an alteration of the immune response, whereas overexpression was reported to be involved in neuroinflammation. However, the regulatory mechanism of GPR34 expression has not yet been investigated. Whole-transcriptome RNA sequencing analysis from spleens and DCs of GPR34 knockout and wild-type mice, combined with protein-protein interaction data, revealed functional modules affected by the absence of this receptor. Among these, NF-kappaB, MAPK, and apoptosis-signaling pathways showed high significance. Using murine DCs we experimentally show that NF-kappaB and MAPK pathways are involved in the downregulation of GPR34. DCs lacking GPR34 have a higher caspase-3/7 activity and increased apoptosis levels. Our study reveals a novel role of GPR34 in the fate of DCs and identifies a regulatory mechanism that could be relevant for treatment of GPR34-overexpressing pathologies, such as neuroinflammatory or cancer conditions. PMID- 26851222 TI - RasGRP1 Is an Essential Signaling Molecule for Development of B1a Cells with Autoantigen Receptors. AB - B1a cells, particularly the PD-L2(+) B1a cell subset, are enriched with autoantigen-specific receptors. However, the underlying molecular mechanism responsible for the skewed selection of autoreactive B1a cells remains unclear. In this study, we find that B1 cells express only Ras guanyl nucleotide-releasing protein (RasGRP) 1, whereas B2 cells express mostly RasGRP3 and little RasGRP1. RasGRP1 is indispensable for transduction of weak signals. RasGRP1 deficiency markedly impairs B1a cell development and reduces serum natural IgM production; in particular, B1a cells that express autoantigen receptors, such as anti phosphatidylcholine B1a cells, are virtually eliminated. Thus, unlike Btk and other signalosome components, RasGRP1 deficiency selectively affects only the B1a cell population with autoantigen receptors rather than the entire pool of B1a cells. PMID- 26851223 TI - Enhanced Cytotoxic CD8 T Cell Priming Using Dendritic Cell-Expressing Human Papillomavirus-16 E6/E7-p16INK4 Fusion Protein with Sequenced Anti-Programmed Death-1. AB - The incidence of human papillomavirus (HPV)-related head and neck squamous cell carcinoma has increased in recent decades, though HPV prevention vaccines may reduce this rise in the future. HPV-related cancers express the viral oncoproteins E6 and E7. The latter inactivates the tumor suppressor protein retinoblastoma (Rb), which leads to the overexpression of p16(INK4) protein, providing unique Ags for therapeutic HPV-specific cancer vaccination. We developed potential adenoviral vaccines that express a fusion protein of HPV-16 E6 and E7 (Ad.E6E7) alone or fused with p16 (Ad.E6E7p16) and also encoding an anti-programmed death (PD)-1 Ab. Human monocyte-derived dendritic cells (DC) transduced with Ad.E6E7 or Ad.E6E7p16 with or without Ad.alphaPD1 were used to activate autologous CD8 CTL in vitro. CTL responses were tested against naturally HPV-infected head and neck squamous cell carcinoma cells using IFN-gamma ELISPOT and [(51)Cr]release assay. Surprisingly, stimulation and antitumor activity of CTL were increased after incubation with Ad.E6E7p16-transduced DC (DC.E6E7p16) compared with Ad.E6E7 (DC.E6E7), a result that may be due to an effect of p16 on cyclin-dependent kinase 4 levels and IL-12 secretion by DC. Moreover, the beneficial effect was most prominent when anti-PD-1 was introduced during the second round of stimulation (after initial priming). These data suggest that careful sequencing of Ad.E6E7.p16 with Ad.alphaPD1 could improve antitumor immunity against HPV-related tumors and that p16 may enhance the immunogenicity of DC, through cyclin-dependent pathways, Th1 cytokine secretion, and by adding a nonviral Ag highly overexpressed in HPV-induced cancers. PMID- 26851225 TI - GED: a manually curated comprehensive resource for epigenetic modification of gametogenesis. AB - Reproductive infertility affects seventh of couples, which is most attributed to the obstacle of gametogenesis. Characterizing the epigenetic modification factors involved in gametogenesis is fundamental to understand the molecular mechanisms and to develop treatments for human infertility. Although the genetic factors have been implicated in gametogenesis, no dedicated bioinformatics resource for gametogenesis is available. To elucidate the relationship of epigenetic modification and mammalian gametogenesis, we developed a new database, gametogenesis epigenetic modification database (GED), a manually curated database, which aims at providing a comprehensive resource of epigenetic modification of gametogenesis. The database integrates three kinds information of epigenetic modifications during gametogenesis (DNA methylation, histone modification and RNA regulation), and the gametogenesis has been detailed as 16 stages in seven mammal species (Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa, Bos taurus, Capra hircus and Ovis aries). Besides, we have predicted the linear pathways of epigenetic modification which were composed of 211 genes/proteins and microRNAs that were involved in gametogenesis. GED is a user friendly Web site, through which users can obtain the comprehensive epigenetic factor information and molecular pathways by visiting our database freely. GED is free available at http://gametsepi.nwsuaflmz.com. PMID- 26851226 TI - Using popular education with health promotion students in the USA. AB - Recent publications have called for new approaches to training the next generation of health promotion professionals, for whom effective practice depends on understanding how systemic inequities are created and function and how they can be dismantled. These approaches gain particular urgency in the context of recent trends toward commodification of knowledge at both the secondary and post secondary levels. Popular education, a liberatory pedagogy, has been used in social movements around the world for decades. In a health promotion context, its use has been associated with increased empowerment and improved health. To explore the potential of popular education (PE) for helping health promotion students develop a systemic analysis of power and privilege and the concrete skills needed to address health and social inequities, we conducted a case study in the context of a community organizing class in a Master's in Public Health curriculum. Analysis of mixed methods data collected from students suggested that PE, with its focus on concrete practices and interactions, is a valid alternative to conventional pedagogy and a useful complement to liberatory pedagogies more common in university classrooms. Application of PE in higher education will require overcoming barriers, including student resistance and institutional pressures that discourage its use. PMID- 26851224 TI - Bridging semantics and syntax with graph algorithms-state-of-the-art of extracting biomedical relations. AB - Research on extracting biomedical relations has received growing attention recently, with numerous biological and clinical applications including those in pharmacogenomics, clinical trial screening and adverse drug reaction detection. The ability to accurately capture both semantic and syntactic structures in text expressing these relations becomes increasingly critical to enable deep understanding of scientific papers and clinical narratives. Shared task challenges have been organized by both bioinformatics and clinical informatics communities to assess and advance the state-of-the-art research. Significant progress has been made in algorithm development and resource construction. In particular, graph-based approaches bridge semantics and syntax, often achieving the best performance in shared tasks. However, a number of problems at the frontiers of biomedical relation extraction continue to pose interesting challenges and present opportunities for great improvement and fruitful research. In this article, we place biomedical relation extraction against the backdrop of its versatile applications, present a gentle introduction to its general pipeline and shared resources, review the current state-of-the-art in methodology advancement, discuss limitations and point out several promising future directions. PMID- 26851227 TI - Screening accuracy of the parent-completed Ages and Stages Questionnaires - second edition as a broadband screener for motor problems in preschoolers with autism spectrum disorders. AB - Children with autism spectrum disorders are at risk for motor problems. However, this area is often overlooked in the developmental evaluation in autism diagnostic clinics. An alternative can be to identify children who should receive intensive motor assessment by using a parent-based screener. The aim of this study was to examine whether the Ages and Stages Questionnaires - second edition may be used to identify gross and fine motor problems in children. High functioning children with autism spectrum disorder (n = 43, 22-54 m) participated in this study. Sensitivity, specificity, predictive values and areas under the receiver operating characteristic curve were calculated by comparing the Ages and Stages Questionnaires - second edition scores to the developmental evaluation of the Peabody Developmental Motor Scale - second edition. The results revealed that both the Ages and Stages Questionnaires - second edition gross and fine motor domain may be used to identify children without motor problems. In contrast, sensitivity analyses revealed the likelihood of under screening motor problems in this population. The Ages and Stages Questionnaires - second edition met only the criteria of a fair to good accuracy to identify poor gross motor (sensitivity = 100%) and below-average fine motor development (sensitivity = 71%) in this sample. Hence, the capacity of the Ages and Stages Questionnaires - second edition to identify motor problems in preschoolers with autism spectrum disorder appears to be limited. It is recommended to include a formal standardized motor test in the diagnostic procedure for all children with autism spectrum disorder. PMID- 26851228 TI - Parent and health care provider perspectives related to disclosure of autism spectrum disorder in pediatric emergency departments. AB - Children and youth with autism spectrum disorder presenting in emergency departments face potential cognitive, sensory, and behavioral challenges, and it is crucial for providers to be aware of their unique needs. However, disclosure of a child's autism spectrum disorder can be complex for parental caregivers and is not well understood. This qualitative study utilized a grounded theory approach and analyzed data from 28 parents and 16 health care providers related to autism spectrum disorder disclosure within two Canadian pediatric emergency departments. Study results indicated that participants identified benefits and risks of disclosure. Encouraging understanding, expediting service, and preparing health care providers for working with children with autism spectrum disorder were identified as benefits of disclosure. Risks related to disclosure included potential negative attributions toward the children and parental discomfort in disclosing a diagnosis in front of the children. Parents discussed the health care encounters they experienced following disclosure and provided recommendations for improving the disclosure process in the emergency department. It is recommended that future research explore the experiences of parents who choose not to disclose their child's autism spectrum disorder. Greater awareness of the disclosure experience and the development of resources and tools to support communication between parents and health care providers are also recommended. PMID- 26851229 TI - The impact of maternal, child, and family characteristics on the daily well-being and parenting experiences of mothers of children with autism spectrum disorder. AB - This study utilized a daily diaries method to explore the global factors that impact daily general affect and daily parenting interactions of mothers of children with autism spectrum disorder. Eighty-three mothers of a child with autism spectrum disorder between the ages of 3 and 13 years completed global assessments of maternal depressive symptoms, child autism spectrum disorder symptom severity, and family functioning. Mothers then reported on their daily negative and positive affect as well as their daily positive and frustrating parenting interactions for 14 consecutive days. The results indicated that higher levels of maternal depressive symptoms were related to decreased daily positive affect, whereas greater child social motivation impairments were related to increased daily positive affect. Only maternal depressive symptoms were associated with increased daily negative affect. Furthermore, higher levels of family cohesion were related to increased daily positive parenting interactions. Finally, higher maternal depressive symptoms as well as family rigidity were related to increased daily frustrating parenting interactions. Implications for interventions focused on the family system are discussed. PMID- 26851230 TI - Maternal experience of Lego Therapy in families with children with autism spectrum conditions: What is the impact on family relationships? AB - This study aimed to explore mothers' experience of implementing Lego Therapy at home within the family. Following a Lego Therapy training session, mothers carried out hourly sessions with their child with an autism spectrum condition and the child's sibling, once a week, for 6 weeks. Mothers were interviewed following the intervention, and the data were analysed using interpretative phenomenological analysis. Themes emerged around improved family relationships, a positive impact on the child as an individual, and changed maternal, sibling and child perspectives. Challenging and facilitative aspects also emerged, as did some ambivalence about the impact of the intervention in the wider context. The findings are supportive of previous Lego Therapy studies and have implications for strengths-based service provision. PMID- 26851231 TI - Socioeconomic status and intelligence quotient as predictors of psychiatric disorders in children and adolescents with high-functioning autism spectrum disorder and in their siblings. AB - Previous studies have shown high rates of comorbid disorders in children and adolescents with autism spectrum disorder, but failed to compare them with general population and few of them have identified predictors of comorbidity. This study compared the rates of psychiatric disorders in 50 children and adolescents with autism spectrum disorder, 24 of their siblings, 32 controls from general population and 22 of their siblings. Children and adolescent with autism spectrum disorder and their siblings had higher rates of attention deficit and hyperactivity disorder compared to controls. Lower socioeconomic status and intelligence quotient were the main risk factors. The contribution of socioeconomic status and intelligence quotient to increase the risk of developing comorbidity in autism spectrum disorder and psychopathology in their siblings deserves further study. PMID- 26851232 TI - School-based social skills training for preschool-age children with autism spectrum disorder. AB - Individuals with autism spectrum disorder display impairments in social interactions and communication that appear at early ages and result in short- and long-term negative outcomes. As such, there is a need for effective social skills training programs for young children with autism spectrum disorder-particularly interventions capable of being delivered in educational settings. The study evaluated the effects of the Superheroes Social Skills program on accurate demonstration of social skills in young children with autism spectrum disorder. Two preschool-age children with autism spectrum disorder participated in a weekly social skills intervention. A multiple probe design across skills was used to determine the effects of the intervention. Both participants demonstrated substantial improvements in skill accuracy. Social skills checklists also indicated improvements in social functioning over baseline levels. PMID- 26851234 TI - A Computational Modeling Approach for Deriving Biomarkers to Predict Cancer Risk in Premalignant Disease. AB - The lack of effective biomarkers for predicting cancer risk in premalignant disease is a major clinical problem. There is a near-limitless list of candidate biomarkers, and it remains unclear how best to sample the tissue in space and time. Practical constraints mean that only a few of these candidate biomarker strategies can be evaluated empirically, and there is no framework to determine which of the plethora of possibilities is the most promising. Here, we have sought to solve this problem by developing a theoretical platform for in silico biomarker development. We construct a simple computational model of carcinogenesis in premalignant disease and use the model to evaluate an extensive list of tissue sampling strategies and different molecular measures of these samples. Our model predicts that (i) taking more biopsies improves prognostication, but with diminishing returns for each additional biopsy; (ii) longitudinally collected biopsies provide slightly more prognostic information than a single biopsy collected at the latest possible time point; (iii) measurements of clonal diversity are more prognostic than measurements of the presence or absence of a particular abnormality and are particularly robust to confounding by tissue sampling; and (iv) the spatial pattern of clonal expansions is a particularly prognostic measure. This study demonstrates how the use of a mechanistic framework provided by computational modeling can diminish empirical constraints on biomarker development. PMID- 26851233 TI - DNA Methylation of BDNF Gene in Schizophrenia. AB - BACKGROUND Although genetic factors are risk factors for schizophrenia, some environmental factors are thought to be required for the manifestation of disease. Epigenetic mechanisms regulate gene functions without causing a change in the nucleotide sequence of DNA. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that regulates synaptic transmission and plasticity. It has been suggested that BDNF may play a role in the pathophysiology of schizophrenia. It is established that methylation status of the BDNF gene is associated with fear learning, memory, and stressful social interactions. In this study, we aimed to investigate the DNA methylation status of BDNF gene in patients with schizophrenia. MATERIAL AND METHODS The study included 49 patients (33 male and 16 female) with schizophrenia and 65 unrelated healthy controls (46 male and 19 female). Determination of methylation pattern of CpG islands was based on the principle that bisulfite treatment of DNA results in conversion of unmethylated cytosine residues into uracil, whereas methylated cytosine residues remain unmodified. Methylation-specific PCR was performed with primers specific for either methylated or unmethylated DNA. RESULTS There was no significant difference in methylated or un-methylated status for BDNF promoters between schizophrenia patients and controls. The mean duration of illness was significantly lower in the hemi-methylated group compared to the non-methylated group for BDNF gene CpG island-1 in schizophrenia patients. CONCLUSIONS Although there were no differences in BDNF gene methylation status between schizophrenia patients and healthy controls, there was an association between duration of illness and DNA methylation. PMID- 26851235 TI - Hepatic Premalignant Alterations Triggered by Human Nephrotoxin Aristolochic Acid I in Canines. AB - Aristolochic acid I (AAI) existing in plant drugs from Aristolochia species is an environmental human carcinogen associated with urothelial cancer. Although gene association network analysis demonstrated gene expression profile changes in the liver of human TP53 knock-in mice after acute AAI exposure, to date, whether AAI causes hepatic tumorigenesis is still not confirmed. Here, we show that hepatic premalignant alterations appeared in canines after a 10-day AAI oral administration (3 mg/kg/day). We observed c-Myc oncoprotein and oncofetal RNA binding protein Lin28B overexpressions accompanied by cancer progenitor-like cell formation in the liver by AAI exposure. Meanwhile, we found that forkhead box O1 (FOXO1) was robustly phosphorylated, thereby shuttling into the cytoplasm of hepatocytes. Furthermore, utilizing microarray and qRT-PCR analysis, we confirmed that microRNA expression significantly dysregulated in the liver treated with AAI. Among them, we particularly focused on the members in let-7 miRNAs and miR 23a clusters, the downstream of c-Myc and IL6 receptor (IL6R) signaling pathway linking the premalignant alteration. Strikingly, when IL6 was added in vitro, IL6R/NF-kappaB signaling activation contributed to the increase of FOXO1 phosphorylation by the let-7b inhibitor. Therefore, it highlights the new insight into the interplay of the network in hepatic tumorigenesis by AAI exposure, and also suggests that anti-premalignant therapy may be crucial for preventing AAI induced hepatocarcinogenesis. PMID- 26851238 TI - Role of the Apolipoprotein E Polymorphisms in the Development of Retinal Vein Occlusion in a Tunisian Population: A Case-Control Study. AB - Apolipoprotein E ( APOE) is a member of the apolipoprotein gene family. APOE is polymorphic with 3 main allelic types: ?2, ?3, and ?4. Certain of these alleles have been associated with higher vascular risk. However, the association of APOE genotypes with retinal biomarkers and risk of retinal stroke is less clear. This study evaluated the role of APOE polymorphisms in retinal vein occlusion (RVO). In the present study, 2-point mutations coding amino acid residues 112 and 158 were amplified using the polymerase chain reaction (PCR) from DNA extracted from Tunisian participants. APOE genotypes were determined by multiplex PCR followed by molecular hybridization. Eighty-eight patients (26 women and 62 men) and 100 age- and gender-matched healthy participants were enrolled. The statistical study revealed a higher frequency of the ?4 allele in patients as compared to controls (27.3% vs 9%) with a significant association of the ?4 allele with the disease ( P < 10-3, Pa < 10-3, odds ratio [OR] = 3.8, 95% confidence interval [CI] = 2.1 6.8). The frequency of the ?3 allele was significantly lower in the patients with RVO compared to the controls (60.2% vs 82.5%, respectively; P < 10-3, Pa < 10-3, OR = 0.32, 95% CI = 0.19-0.53). The ?3 allele seems to be protective against the disease. There was no association between the APO ?2 allele and RVO. The association of APOE allele and genotype with RVO requires further investigation in different populations. PMID- 26851239 TI - Determination of Human Hepatocyte Intrinsic Clearance for Slowly Metabolized Compounds: Comparison of a Primary Hepatocyte/Stromal Cell Co-culture with Plated Primary Hepatocytes and HepaRG. AB - A key requirement in drug discovery is to accurately define intrinsic clearance (CL(int)) values of less than 1 ul/min/10(6) hepatocytes, which requires assays that allow for longer incubation time as a complement to suspended hepatocytes. This study assessed the effectiveness of plated HepaRG cells, plated primary human hepatocytes (PHHs), and the HuREL human hepatocyte/stromal cell co-cultures for determination of low CL(int) values. The investigation demonstrated that the systems were capable of providing statistically significant CL(int) estimations down to 0.2 ul/min/10(6) cells. The HuREL assay provided a higher level of reproducibility, with repeat significant CL(int) values being defined in a minimum of triplicate consecutive assays for six of seven of the low CL(int) compounds compared with four of seven for PHHs and two of seven for HepaRG. The assays were also compared with a suspension assay using drugs with higher CL(int) values and diverse enzymology. The CL(int) values from the PHH and HuREL assays were similar to those defined by a hepatocyte suspension assay, indicating that they can be used interchangeably alongside a standard assay. Finally, data from these two assays could also predict in vivo hepatic metabolic CL(int) to within 3 fold for greater than 70% of the compounds tested, with average fold errors (AFE) of 1.6 and 2.3, respectively, whereas the HepaRG data were predictive to within 3 fold for only 50% of compounds (AFE 2.9). In summary, all systems have utility for low CL(int) determination, but the HuREL co-culture appears slightly superior regarding overall assay performance. PMID- 26851240 TI - Correlation between Conjugated Bisphenol A Concentrations and Efflux Transporter Expression in Human Fetal Livers. AB - Because of its widespread use in the manufacturing of consumer products over several decades, human exposure to bisphenol A (BPA) has been pervasive. Fetuses are particularly sensitive to BPA exposure, with a number of negative developmental and reproductive outcomes observed in rodent perinatal models. Xenobiotic transporters are one mechanism to extrude conjugated and unconjugated BPA from the liver. In this study, the mRNA expression of xenobiotic transporters and relationships with total, conjugated, and free BPA levels were explored utilizing human fetal liver samples. The mRNA expression of breast cancer resistance protein (BCRP) and multidrug resistance-associated transporter (MRP)4, as well as BCRP and multidrug resistance transporter 1 exhibited the highest degree of correlation, with r(2) values of 0.941 and 0.816 (P < 0.001 for both), respectively. Increasing concentrations of conjugated BPA significantly correlated with high expression of MRP1 (P < 0.001), MRP2 (P < 0.05), and MRP3 (P < 0.05) transporters, in addition to the NF-E2-related factor 2 transcription factor (P < 0.001) and its prototypical target gene, NAD(P)H quinone oxidoreductase 1 (P < 0.001). These data demonstrate that xenobiotic transporters may be coordinately expressed in the human fetal liver. This is also the first report of a relationship between environmentally relevant fetal BPA levels and differences in the expression of transporters that can excrete the parent compound and its metabolites. PMID- 26851241 TI - Inactivation of CYP2A6 by the Dietary Phenylpropanoid trans-Cinnamic Aldehyde (Cinnamaldehyde) and Estimation of Interactions with Nicotine and Letrozole. AB - Human exposure to trans-cinnamic aldehyde [t-CA; cinnamaldehyde; cinnamal; (E)-3 phenylprop-2-enal] is common through diet and through the use of cinnamon powder for diabetes and to provide flavor and scent in commercial products. We evaluated the likelihood of t-CA to influence metabolism by inhibition of P450 enzymes. IC50 values from recombinant enzymes indicated that an interaction is most probable for CYP2A6 (IC50 = 6.1 uM). t-CA was 10.5-fold more selective for human CYP2A6 than for CYP2E1; IC50 values for P450s 1A2, 2B6, 2C9, 2C19, 2D6, and 3A4 were 15.8-fold higher or more. t-CA is a type I ligand for CYP2A6 (KS = 14.9 uM). Inhibition of CYP2A6 by t-CA was metabolism-dependent; inhibition required NADPH and increased with time. Glutathione lessened the extent of inhibition modestly and statistically significantly. The carbon monoxide binding spectrum was dramatically diminished after exposure to NADPH and t-CA, suggesting degradation of the heme or CYP2A6 apoprotein. Using a static model and mechanism-based inhibition parameters (K(I) = 18.0 uM; k(inact) = 0.056 minute(-1)), changes in the area under the concentration-time curve (AUC) for nicotine and letrozole were predicted in the presence of t-CA (0.1 and 1 uM). The AUC fold-change ranged from 1.1 to 3.6. In summary, t-CA is a potential source of pharmacokinetic variability for CYP2A6 substrates due to metabolism-dependent inhibition, especially in scenarios when exposure to t-CA is elevated due to high dietary exposure, or when cinnamon is used as a treatment of specific disease states (e.g., diabetes). PMID- 26851243 TI - Comparing smartphone camera adapters in imaging post-operative cataract patients. AB - Introduction The goal of this study is to compare image quality and clinical confidence for managing post-operative cataract patients based on anterior segment smartphone images obtained in real-world settings using four types of adapters: (a) macro lens (ML), (b) ML with augmented light-emitting diode (LED) illumination (ML-LED), (c) no adapter (NA) and (d) slit lamp (SL) adapter. Methods Anterior segment images were obtained from 190 eyes after cataract surgery using an eight-megapixel iPhone 6 smartphone camera with four adapters: ML, ML-LED, NA, and SL. Smartphone images were subjectively rated by ophthalmologists as acceptable or not acceptable for: (a) image quality for evaluating the anterior segment structures and (b) reader confidence in clinically managing post-operative patients based on smartphone images. Results NA, ML-LED, and SL had the highest scores for image quality with 100%, 93.7%, and 86.3% judged as acceptable, respectively. NA, SL, and ML-LED were also rated highest in clinical confidence with 100%, 98%, and 93.2% having acceptable levels, respectively. ML was judged lowest in both image quality (61.1% acceptable) and clinical confidence (37.4% acceptable). Discussion This study represents the first effort to compare different smartphone camera adapters' ability to image the anterior segment of the eye in a real-world setting. Our study shows that ML-LED, NA, and SL adapters were acceptable for visualizing anterior segment structures to physician readers in 86-100% of cases. When coupled with visual acuity, intro-ocular pressure and history, these images can result in acceptable clinical confidence in 93-100% of cases. PMID- 26851242 TI - The Role of Protein-Protein and Protein-Membrane Interactions on P450 Function. AB - This symposium summary, sponsored by the ASPET, was held at Experimental Biology 2015 on March 29, 2015, in Boston, Massachusetts. The symposium focused on: 1) the interactions of cytochrome P450s (P450s) with their redox partners; and 2) the role of the lipid membrane in their orientation and stabilization. Two presentations discussed the interactions of P450s with NADPH-P450 reductase (CPR) and cytochrome b5. First, solution nuclear magnetic resonance was used to compare the protein interactions that facilitated either the hydroxylase or lyase activities of CYP17A1. The lyase interaction was stimulated by the presence of b5 and 17alpha-hydroxypregnenolone, whereas the hydroxylase reaction was predominant in the absence of b5. The role of b5 was also shown in vivo by selective hepatic knockout of b5 from mice expressing CYP3A4 and CYP2D6; the lack of b5 caused a decrease in the clearance of several substrates. The role of the membrane on P450 orientation was examined using computational methods, showing that the proximal region of the P450 molecule faced the aqueous phase. The distal region, containing the substrate-access channel, was associated with the membrane. The interaction of NADPH-P450 reductase (CPR) with the membrane was also described, showing the ability of CPR to "helicopter" above the membrane. Finally, the endoplasmic reticulum (ER) was shown to be heterogeneous, having ordered membrane regions containing cholesterol and more disordered regions. Interestingly, two closely related P450s, CYP1A1 and CYP1A2, resided in different regions of the ER. The structural characteristics of their localization were examined. These studies emphasize the importance of P450 protein organization to their function. PMID- 26851245 TI - Calmodulin kinase II inhibition limits the pro-arrhythmic Ca2+ waves induced by cAMP-phosphodiesterase inhibitors. AB - AIMS: A major concern of using phosphodiesterase (PDE) inhibitors in heart failure is their potential to increase mortality by inducing arrhythmias. By diminishing cyclic adenosine monophosphate (cAMP) hydrolysis, they promote protein kinase A (PKA) activity under beta-adrenergic receptor (beta-AR) stimulation, hence enhancing Ca(2+) cycling and contraction. Yet, cAMP also activates CaMKII via PKA or the exchange protein Epac, but it remains unknown whether these pathways are involved in the pro-arrhythmic effect of PDE inhibitors. METHODS AND RESULTS: Excitation-contraction coupling was investigated in isolated adult rat ventricular myocytes loaded with Fura-2 and paced at 1 Hz allowing coincident measurement of intracellular Ca(2+) and sarcomere shortening. The PDE4 inhibitor Ro 20-1724 (Ro) promoted the inotropic effects of the non selective beta-AR agonist isoprenaline (Iso) and also spontaneous diastolic Ca(2+) waves (SCWs). PDE4 inhibition potentiated RyR2 and PLB phosphorylation at specific PKA and CaMKII sites increasing sarcoplasmic reticulum (SR) Ca(2+) load and SR Ca(2+) leak measured in a 0Na(+)/0Ca(2+) solution +/- tetracaine. PKA inhibition suppressed all the effects of Iso +/- Ro, whereas CaMKII inhibition prevented SR Ca(2+) leak and diminished SCW incidence without affecting the inotropic effects of Ro. Inhibition of Epac2 but not Epac1 diminished the occurrence of SCWs. PDE3 inhibition with cilostamide induced an SR Ca(2+) leak, which was also blocked by CaMKII inhibition. CONCLUSION: Our results show that PDE inhibitors exert inotropic effects via PKA but lead to SCWs via both PKA and CaMKII activation partly via Epac2, suggesting the potential use of CaMKII inhibitors as adjuncts to PDE inhibition to limit their pro-arrhythmic effects. PMID- 26851244 TI - Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas. AB - Immobilization is a form of disuse characterized by a loss of strength and muscle mass. Among the main features are decreased IGF-1/Akt signalling and increased ubiquitin-proteasome pathway signalling, which induce greater myosin heavy chain degradation. Activation of the classical renin-angiotensin system (RAS) causes deleterious effects in skeletal muscle, including muscle wasting. In contrast, angiotensin-(1-7) [Ang-(1-7)], a peptide of the non-classical RAS, produces beneficial effects in skeletal muscle. However, the role of Ang-(1-7) in skeletal muscle disuse atrophy and independent of classical RAS activation has not been evaluated. Therefore, we assessed the functions of Ang-(1-7) and the Mas receptor in disuse muscle atrophyin vivousing unilateral cast immobilization of the hind limb in male, 12-week-old wild-type (WT) and Mas-knockout (Mas KO) mice for 1 and 14 days. Additionally, we evaluated the participation of IGF-1/IGFR-1/Akt signalling and ubiquitin-proteasome pathway expression on the effects of Ang-(1 7) immobilization-induced muscle atrophy. Our results found that Ang-(1-7) prevented decreased muscle strength and reduced myofiber diameter, myosin heavy chain levels, and the induction of atrogin-1 and MuRF-1 expressions, all of which normally occur during immobilization. Analyses indicated that Ang-(1-7) increases IGF-1/IGFR-1/Akt pathway signalling through IGFR-1 and Akt phosphorylation, and the concomitant activation of two downstream targets of Akt, p70S6K and FoxO3. These anti-atrophic effects of Ang-(1-7) were not observed in Mas KO mice, indicating crucial participation of the Mas receptor. This report is the first to propose anti-atrophic effects of Ang-(1-7) via the Mas receptor and the participation of the IGF-1/IGFR-1/Akt/p70S6K/FoxO3 mechanism in disuse skeletal muscle atrophy. PMID- 26851248 TI - Refinement of habituation procedures in diet-induced obese mice. AB - Orogastric gavage, while a common method for delivering experimental substances in mice, has been shown to induce stress. To minimize the associated stress with this procedure, sham gavage prior to the start of experiment is a common method for habiutating mice. We investigated whether handling and restraint could replace sham treatment in the acclimatization protocol. Mice were either undisturbed, hand-restrained for 10 s or sham-gavaged daily for six days prior to eight days of twice daily gavage. The results showed that repetitive restraint and gavage had no differences in body weight after eight days of treatment compared with the body weights at the start of treatment, whereas animals left undisturbed lost significant weight once treatment began. These data suggest that procedure refinement by replacing sham treatment with hand restraint is sufficient to acclimatize mice to the stress associated with gavage. PMID- 26851246 TI - Estrogen and testosterone in concert with EFNB3 regulate vascular smooth muscle cell contractility and blood pressure. AB - EPH kinases and their ligands, ephrins (EFNs), have vital and diverse biological functions, although their function in blood pressure (BP) control has not been studied in detail. In the present study, we report that Efnb3 gene knockout (KO) led to increased BP in female but not male mice. Vascular smooth muscle cells (VSMCs) were target cells for EFNB3 function in BP regulation. The deletion of EFNB3 augmented contractility of VSMCs from female but not male KO mice, compared with their wild-type (WT) counterparts. Estrogen augmented VSMC contractility while testosterone reduced it in the absence of EFNB3, although these sex hormones had no effect on the contractility of VSMCs from WT mice. The effect of estrogen on KO VSMC contractility was via a nongenomic pathway involving GPER, while that of testosterone was likely via a genomic pathway, according to VSMC contractility assays and GPER knockdown assays. The sex hormone-dependent contraction phenotypes in KO VSMCs were reflected in BP in vivo. Ovariectomy rendered female KO mice normotensive. At the molecular level, EFNB3 KO in VSMCs resulted in reduced myosin light chain kinase phosphorylation, an event enhancing sensitivity to Ca(2+)flux in VSMCs. Our investigation has revealed previously unknown EFNB3 functions in BP regulation and show that EFNB3 might be a hypertension risk gene in certain individuals. PMID- 26851247 TI - Hypoxia-induced cardiac injury in dystrophic mice. AB - Duchenne muscular dystrophy (DMD) is a disease of progressive destruction of striated muscle, resulting in muscle weakness with progressive respiratory and cardiac failure. Respiratory and cardiac disease are the leading causes of death in DMD patients. Previous studies have suggested an important link between cardiac dysfunction and hypoxia in the dystrophic heart; these studies aim to understand the mechanism underlying this connection. Here we demonstrate that anesthetized dystrophic mice display significant mortality following acute exposure to hypoxia. This increased mortality is associated with a significant metabolic acidosis, despite having significantly higher levels of arterial Po2 Chronic hypoxia does not result in mortality, but rather is characterized by marked cardiac fibrosis. Studies in isolated hearts reveal that the contractile function of dystrophic hearts is highly susceptible to short bouts of ischemia, but these hearts tolerate prolonged acidosis better than wild-type hearts, indicating an increased sensitivity of the dystrophic heart to hypoxia. Dystrophic hearts display decreased cardiac efficiency and oxygen extraction. Isolated dystrophic cardiomyocytes and hearts have normal levels of FCCP-induced oxygen consumption, and mitochondrial morphology and content are normal in the dystrophic heart. These studies demonstrate reductions in cardiac efficiency and oxygen extraction of the dystrophic heart. The underlying cause of this reduced oxygen extraction is not clear; however, the current studies suggest that large disruptions of mitochondrial respiratory function or coronary flow regulation are not responsible. This finding is significant, as hypoxia is a common and largely preventable component of DMD that may contribute to the progression of the cardiac disease in DMD patients. PMID- 26851249 TI - A study of the psychometric properties of 12-item World Health Organization Disability Assessment Schedule 2.0 in a large population of people with chronic musculoskeletal pain. AB - OBJECTIVE: To assess the validity of the Finnish translation of the 12-item World Health Organization Disability Assessment Schedule (WHODAS 2.0). DESIGN: Cross sectional cohort survey study. SETTING: Physical and Rehabilitation Medicine outpatient university clinic. SUBJECTS: The 501 consecutive patients with chronic musculoskeletal pain. MAIN MEASURES: Exploratory factor analysis and a graded response model using item response theory analysis were used to assess the constructs and discrimination ability of WHODAS 2.0. RESULTS: The exploratory factor analysis revealed two retained factors with eigenvalues 5.15 and 1.04. Discrimination ability of all items was high or perfect, varying from 1.2 to 2.5. The difficulty levels of seven out of 12 items were shifted towards the elevated disability level. As a result, the entire test characteristic curve showed a shift towards higher levels of disability, placing it at the point of disability level of +1 (where 0 indicates the average level of disability within the sample). CONCLUSIONS: The present data indicate that the Finnish translation of the 12-item WHODAS 2.0 is a valid instrument for measuring restrictions of activity and participation among patients with chronic musculoskeletal pain. PMID- 26851250 TI - Very early social support following mild stroke is associated with emotional and behavioral outcomes three months later. AB - OBJECTIVE: To investigate whether social contact and support received during hospitalization for acute ischemic stroke predict depression and daily life functioning three months later. DESIGN: Prospective observational study using Ecological Momentary Assessments to evaluate the number of social contacts as well as social support received from family, friends and medical staff within 24 hours following admission for stroke. Patients also monitored depression symptoms and behavior in real-time and in daily life contexts three months later. SETTING: A university hospital acute stroke unit. SUBJECTS: Thirty-four mild ischemic stroke patients. INTERVENTIONS: None. MAIN MEASURES: One-day Ecological Momentary Assessments immediately following stroke collected information concerning perceived social support, number of social contacts and depression symptoms. Ecological Momentary Assessments was repeated three months later and addressed depression levels as well as activities of daily living, such as working, cooking, shopping and housework. RESULTS: The number of social interactions received at hospitalization did not predict three-month outcomes. However, a better quality of moral support from friends and family immediately after stroke was associated with decreases in later depression levels ( p = 0.041) and increases in activities of daily living ( p = 0.011). Material support from friends and family was associated with increases in activities of daily living ( p = 0.012). No effect was observed for support received from medical staff. CONCLUSIONS: Patient perceptions of better support quality, and not quantity, immediately following mild stroke, are associated with better behavioral and emotional outcomes three months later. PMID- 26851251 TI - Description of load progression and pain response during progressive resistance training early after total hip arthroplasty: secondary analyses from a randomized controlled trial. AB - OBJECTIVE: To describe a progressive resistance training intervention implemented shortly after total hip arthroplasty, including a detailed description of load progression, pain response and adverse events to the training. DESIGN: Secondary analyses of data from the intervention group in a randomized controlled trial. SUBJECTS: This study reports data from the intervention group ( n = 37). INTERVENTIONS: The protocol described supervised progressive resistance training of the operated leg two days/week in addition to home-based exercise five days/week and for 10 weeks. The relative load progressed from 12 repetition maximum to 8 repetition maximum during 10 weeks for the exercises: knee extension, hip abduction, -flexion and -extension. MAIN MEASURES: Training load in kilograms (kg) for each exercise, hip pain during, before and after exercise using the Visual Analog Scale and adverse events during the initial four weeks of training. RESULTS: The majority of patients experienced only moderate hip pain during exercise (range in median across exercises and sessions: 5-35 mm Visual Analog Scale) and mild pain at rest (median: 1-18 mm Visual Analog Scale), both of which decreased over time ( p < 0.001), despite a substantial increase in absolute training load (67%-166 % across exercises, p < 0.001). Out of 152 training sessions, short term pain response (an increase >20 mm Visual Analog Scale) occurred in 13 patients in 24 training sessions. CONCLUSION: Progressive resistance training as described in the present study can be implemented shortly following total hip arthroplasty with substantial load progression and no overall exacerbation of postoperative pain. Some patients may experience a short term pain response. Trial Registration (primary trial): NCT01214954. PMID- 26851252 TI - Berberine induces dedifferentiation by actin cytoskeleton reorganization via phosphoinositide 3-kinase/Akt and p38 kinase pathways in rabbit articular chondrocytes. AB - Osteoarthritis is a nonrheumatologic joint disease characterized by progressive degeneration of the cartilage extracellular matrix. Berberine (BBR) is an isoquinoline alkaloid used in traditional Chinese medicine, the majority of which is extracted from Huang Lian (Coptis chinensis). Although numerous studies have revealed the anticancer activity of BBR, its effects on normal cells, such as chondrocytes, and the molecular mechanisms underlying its actions remain elusive. Therefore, we examined the effects of BBR on rabbit articular chondrocytes, and the underlying molecular mechanisms, focusing on actin cytoskeletal reorganization. BBR induced dedifferentiation by inhibiting activation of phosphoinositide-3(PI3)-kinase/Akt and p38 kinase. Furthermore, inhibition of p38 kinase and PI3-kinase/Akt with SB203580 and LY294002, respectively, accelerated the BBR-induced dedifferentiation. BBR also caused actin cytoskeletal architecture reorganization and, therefore, we investigated if these effects were involved in the dedifferentiation. Disruption of the actin cytoskeleton by cytochalasin D reversed the BBR-induced dedifferentiation by activating PI3 kinase/Akt and p38 kinase. In contrast, the induction of actin filament aggregation by jasplakinolide accelerated the BBR-induced dedifferentiation via PI3-kinase/Akt inhibition and p38 kinase activation. Taken together, these data suggest that BBR strongly induces dedifferentiation, and actin cytoskeletal reorganization is a crucial requirement for this effect. Furthermore, the dedifferentiation activity of BBR appears to be mediated via PI3-kinase/Akt and p38 kinase pathways in rabbit articular chondrocytes. PMID- 26851253 TI - 'Too much of a coincidence': identical twins with exertional heatstroke in the same race. AB - This report discusses a unique case of monozygotic male twins who both collapsed with exertional heat stroke (EHS) during the same marathon in relatively cool conditions. The twins were official race pacers in a popular city marathon held in the early spring in the UK. Both recovered uneventfully due to the prompt recognition of EHS and use of aggressive cooling measures, which prevented life threatening complications. The case illustrates that EHS is a complex illness with a possible genetic predisposition, which can occur among runners even in cooler conditions. This link is explored together with the influence of their role as race pacers and the additional backpack worn in the development of EHS. PMID- 26851254 TI - State of diagnostic quandary solved by modern technology: a rare case of Madelung's disease. AB - Madelung's disease is a neglected metabolic disease characterised by generalised multiple fatty tissue deposits. A 64-year-old Caucasian woman presented with generalised weakness and symptomatic hypoglycaemia with altered mental status. Physical examination showed very distinct physical characteristics with multiple lumps distributed over the upper body. Her neurological symptoms were solved by giving intravenous glucose and optimisation of medical treatment. Even though she had unique characteristics of Madelung's disease, many physicians, on several occasions, failed to recognise her 'hidden diagnosis'. This diagnostic uncertainty was able to be solved by searching the Internet for similar clinical features and images. This case demonstrates characteristics and unique features of a rare disease that can be seen in a female patient even though it is mostly found in males. PMID- 26851255 TI - Penile gangrene as a sign of uncontrolled diabetes mellitus. PMID- 26851256 TI - Testing for Response Shift Bias in Evaluations of School Antibullying Programs. AB - BACKGROUND: Involvement in bullying at school is detrimental to students' mental and physical health; however, school antibullying programs have not been found to be uniformly successful. Self-reported frequency of involvement in bullying victimization and perpetration, often used as outcome measures in intervention impact evaluation studies, may be subject to response shift, particularly in intervention conditions. Such differential shifts could lead to biased estimates of intervention effects. OBJECTIVES: This study investigated the presence of reconceptualization, reprioritization, and recalibration response shift, resulting from intervention implementation. METHOD: The study subjects were Grade 8 students (n = 3,382, 53% female) in the 35 schools participating in the Cyber Friendly Schools Project, a longitudinal group-randomized intervention trial. Response shift was assessed by comparing traditional and retrospective pretest measures of bullying involvement, as well as testing for measurement invariance over time in the Forms of Bullying Scale (FBS) using confirmatory factor analyses. RESULTS: No evidence of response shift was found, indicating students' understandings of bullying behavior remained stable over time. These findings also demonstrate the applicability of the FBS in longitudinal studies involving adolescents. CONCLUSION: While response shift was not present in our study, researchers conducting program evaluations in other contexts are advised to consider testing for this potential source of bias in their studies. PMID- 26851257 TI - Thrombin stimulates albumin transcytosis in lung microvascular endothelial cells via activation of acid sphingomyelinase. AB - Transcellular albumin transport occurs via caveolae that are abundant in lung microvascular endothelial cells. Stimulation of albumin transcytosis by proinflammatory mediators may contribute to alveolar protein leak in lung injury, yet the regulation of albumin transport and its underlying molecular mechanisms are so far incompletely understood. Here we tested the hypothesis that thrombin may stimulate transcellular albumin transport across lung microvascular endothelial cells in an acid-sphingomyelinase dependent manner. Thrombin increased the transport of fluorescently labeled albumin across confluent human lung microvascular endothelial cell (HMVEC-L) monolayers to an extent that markedly exceeds the rate of passive diffusion. Thrombin activated acid sphingomyelinase (ASM) and increased ceramide production in HMVEC-L, but not in bovine pulmonary artery cells, which showed little albumin transport in response to thrombin. Thrombin increased total caveolin-1 (cav-1) content in both whole cell lysates and lipid rafts from HMVEC-L, and this effect was blocked by inhibition of ASM or de novo protein biosynthesis. Thrombin-induced uptake of albumin into lung microvascular endothelial cells was confirmed in isolated perfused lungs by real-time fluorescence imaging and electron microscopy of gold labeled albumin. Inhibition of ASM attenuated thrombin-induced albumin transport both in confluent HMVEC-L and in intact lungs, whereas HMVEC-L treatment with exogenous ASM increased albumin transport and enriched lipid rafts in cav-1. Our findings indicate that thrombin stimulates transcellular albumin transport in an acid sphingomyelinase-dependent manner by inducing de novo synthesis of cav-1 and its recruitment to membrane lipid rafts. PMID- 26851258 TI - Fractal analysis of alveolarization in hyperoxia-induced rat models of bronchopulmonary dysplasia. AB - No papers are available about potentiality of fractal analysis in quantitative assessment of alveolarization in bronchopulmonary dysplasia (BPD). Thus, we here performed a comparative analysis between fractal [fractal dimension (D) and lacunarity] and stereological [mean linear intercept (Lm), total volume of alveolar air spaces, total number of alveoli, mean alveolar volume, total volume and surface area of alveolar septa, and mean alveolar septal thickness] parameters in experimental hyperoxia-induced models of BPD. At birth, rats were distributed between the following groups: 1) rats raised in ambient air for 2 wk; 2) rats exposed to 60% oxygen for 2 wk; 3) rats raised in normoxia for 6 wk; and 4) rats exposed to 60% hyperoxia for 2 wk and to room air for further 4 wk. Normoxic 6-wk rats showed increased D and decreased lacunarity with respect to normoxic 2-wk rats, together with changes in all stereological parameters except for mean alveolar volume. Hyperoxia-exposed 2-wk rats showed significant changes only in total number of alveoli, mean alveolar volume, and lacunarity with respect to equal-in-age normoxic rats. In the comparison between 6-wk rats, the hyperoxia-exposed group showed decreased D and increased lacunarity, together with changes in all stereological parameters except for septal thickness. Analysis of receiver operating characteristic curves showed a comparable discriminatory power of D, lacunarity, and total number of alveoli; Lm and mean alveolar volume were less discriminative. D and lacunarity did not show significant changes when different segmentation thresholds were applied, suggesting that the fractal approach may be fit to automatic image analysis. PMID- 26851260 TI - Treatment with intranasal iloprost reduces disease manifestations in a murine model of previously established COPD. AB - Pulmonary endothelial prostacyclin appears to be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). The effect of treatment with a prostacyclin analog in animal models of previously established COPD is unknown. We evaluated the short- and long-term effect of iloprost on inflammation and airway hyperresponsiveness (AHR) in a murine model of COPD. Nineteen mice were exposed to LPS/elastase, followed by either three doses of intranasal iloprost or saline. In the long-term treatment experiment, 18 mice were exposed to LPS/elastase and then received 6 wk of iloprost or were left untreated as controls. In the short-term experiment, iloprost did not change AHR but significantly reduced serum IL-5 and IFN-gamma. Long-term treatment with iloprost for both 2 and 6 wk significantly improved AHR. After 6 wk of iloprost, there was a reduction in bronchoalveolar lavage (BALF) neutrophils, serum IL-1beta (30.0 +/ 9.2 vs. 64.8 +/- 7.4 pg/ml, P = 0.045), IL-2 (36.5 +/- 10.6 vs. 83.8 +/- 0.4 pg/ml, P = 0.01), IL-10 (75.7 +/- 9.3 vs. 96.5 +/- 3.5 pg/ml, P = 0.02), and nitrite (15.1 +/- 5.4 vs. 30.5 +/- 10.7 MUmol, P = 0.01). Smooth muscle actin (SMA) in the lung homogenate was also significantly reduced after iloprost treatment (P = 0.02), and SMA thickness was reduced in the small and medium blood vessels after iloprost (P < 0.001). In summary, short- and long-term treatment with intranasal iloprost significantly reduced systemic inflammation in an LPS/elastase COPD model. Long-term iloprost treatment also reduced AHR, serum nitrite, SMA, and BALF neutrophilia. These data encourage future investigations of prostanoid therapy as a novel treatment for COPD patients. PMID- 26851259 TI - Increased susceptibility of Cftr-/- mice to LPS-induced lung remodeling. AB - Cystic fibrosis (CF) is caused by homozygous mutations of the CF transmembrane conductance regulator (CFTR) Cl(-) channel, which result in chronic pulmonary infection and inflammation, the major cause of morbidity and mortality. Although these processes are clearly related to each other, each is likely to contribute to the pathology differently. Understanding the contribution of each of these processes to the overall pathology has been difficult, because they are usually so intimately connected. Various CF mouse models have demonstrated abnormal immune responses compared with wild-type (WT) littermates when challenged with live bacteria or bacterial products acutely. However, these studies have not investigated the consequences of persistent inflammation on lung tissue in CF mice, which may better model the lung pathology in patients. We characterized the lung pathology and immune response of Cftr(-/-) (CF) and Cftr(+/+) (WT) mice to chronic administration of Pseudomonas aeruginosa lipopolysaccharide (LPS). We show that, after long-term repeated LPS exposure, CF mice develop an abnormal and persistent immune response, which is associated with more robust structural changes in the lung than those observed in WT mice. Although CF mice and their WT littermates develop lung pathology after chronic exposure to LPS, the inflammation and damage resolve in WT mice. However, CF mice do not recover efficiently, and, as a consequence of their chronic inflammation, CF mice are more susceptible to morphological changes and lung remodeling. This study shows that chronic inflammation alone contributes significantly to aspects of CF lung pathology. PMID- 26851262 TI - Electrophysiological characterization of voltage-dependent calcium currents and TRPV4 currents in human pulmonary fibroblasts. AB - We have presented indirect evidence of a key role for voltage-dependent Ca(2+) currents in TGFbeta-induced synthetic function in human pulmonary fibroblast (HPF), as well as in bleomycin-induced pulmonary fibrosis in mice. Others, however, have provided indirect evidence for transient receptor potential vanilloid 4 (TRPV4) channels in both of those effects. Unfortunately, definitive electrophysiological descriptions of both currents in HPFs have been entirely lacking. In this study, we provide the first direct electrophysiological and pharmacological evidence of the currents in HPFs at rest and during overnight stimulation with TGFbeta. These currents include a Ca(2+)-dependent K(+) current, a TRPV4 current, a chloride current, and an L-type voltage-dependent Ca(2+) current. Evidence for the TRPV4 current include activation of a large-conductance change by two putatively TRPV4-selective agonists (4alpha-phorbol-12,13 didecanoate; GSK1016790A), with a reversal potential near 0 mV, partial sensitivity to two different TRPV4-selective blockers (RN1734; HC067047), and partial reduction following removal of external Na(+) Substantial reduction of the evoked current was seen following the coapplication of RN1734, DIDS, and niflumic acid, suggesting that a chloride current is also involved. The voltage dependent Ca(2+) current is found to be "L-type" in nature, as indicated by the voltage and time dependence of its activation, deactivation, and inactivation properties, and by its pharmacology (sensitivity to replacement with barium and inhibition by nifedipine, verapamil, or mibefradil). We also found that overnight treatment with TGFbeta evoked a periodic current (inward at negative holding potentials, with reversal potential near 0 mV), which is sufficient to trigger the voltage-dependent Ca(2+) currents and, thereby, account for the rhythmic Ca(2+) oscillations, which we have described previously in these cells. PMID- 26851263 TI - Reading Balint group work through Lacan's theory of the four discourses. AB - In Balint groups, (para)medical professionals explore difficult interactions with patients by means of case presentations and discussions. As the process of Balint group work is not well understood, this article investigates Balint group meetings by making use of Lacan's theory of the four discourses. Five Balint group case presentations and their subsequent group discussion were studied, resulting in the observation of five crucial aspects of Balint group work. First, Balint group participants brought puzzlement to the group, which is indicative of the structural impossibility Lacan situates at the basis of all discourse (1). As for the group discussion, we emphasize 'hysterization' as a crucial process in Balint group work (2), the supporting role of the discourse of the analyst (3) and the centrality of discourse interactions (4). Finally, the potential transformation of the initial puzzlement is discussed (5). We conclude by putting forth the uniqueness of Balint group work as well as the potential usefulness of our analysis as a framework for Balint group leaders and professionals in charge of continuing medical education. PMID- 26851261 TI - Regulation of myofibroblast differentiation by cardiac glycosides. AB - Myofibroblast differentiation is a key process in pathogenesis of fibrotic diseases. Cardiac glycosides (ouabain, digoxin) inhibit Na(+)-K(+)-ATPase, resulting in increased intracellular [Na(+)]-to-[K(+)] ratio in cells. Microarray analysis suggested that increased intracellular [Na(+)]/[K(+)] ratio may promote the expression of cyclooxygenase-2 (COX-2), a critical enzyme in the synthesis of prostaglandins. Given antifibrotic effects of prostaglandins through activation of protein kinase A (PKA), we examined if cardiac glycosides stimulate COX-2 expression in human lung fibroblasts and how they affect myofibroblast differentiation. Ouabain stimulated a profound COX-2 expression and a sustained PKA activation, which was blocked by COX-2 inhibitor or by COX-2 knockdown. Ouabain-induced COX-2 expression and PKA activation were abolished by the inhibitor of the Na(+)/Ca(2+) exchanger, KB-R4943. Ouabain inhibited transforming growth factor-beta (TGF-beta)-induced Rho activation, stress fiber formation, serum response factor activation, and the expression of smooth muscle alpha actin, collagen-1, and fibronectin. These effects were recapitulated by an increase in intracellular [Na(+)]/[K(+)] ratio through the treatment of cells with K(+)-free medium or with digoxin. Although inhibition of COX-2 or of the Na(+)/Ca(2+) exchanger blocked ouabain-induced PKA activation, this failed to reverse the inhibition of TGF-beta-induced Rho activation or myofibroblast differentiation by ouabain. Together, these data demonstrate that ouabain, through the increase in intracellular [Na(+)]/[K(+)] ratio, drives the induction of COX-2 expression and PKA activation, which is accompanied by a decreased Rho activation and myofibroblast differentiation in response to TGF-beta. However, COX-2 expression and PKA activation are not sufficient for inhibition of the fibrotic effects of TGF-beta by ouabain, suggesting that additional mechanisms must exist. PMID- 26851264 TI - Producing, ratifying, and resisting support in an online support forum. AB - Previous research examining online support forums has tended to focus either on evaluating their effectiveness while paying limited or no attention to the details of the interactions therein, or on features of their social organization, without regard to their effectiveness in fulfilling their stated purposes. In this article, we consider both the interactional features of a forum and participants' treatment thereof as being effective (or otherwise), thus adopting a view of effectiveness grounded in participants' proximate orientations and actions. Our analysis demonstrates some ways in which participants produce ratified displays of empathy in response to troubles expressed by another, as well as considering some designedly supportive actions that are treated by their recipients as unsupportive or antagonistic. Our findings indicate some structural features of such forums that facilitate the production of support, while suggesting that claims of knowledge tend to be treated as a basis of resistance to ostensibly supportive actions. PMID- 26851265 TI - Struggling to care: A discursive-material analysis of negotiating agency among HIV-positive MSM. AB - A discursive-materialist framework of agency asserts the mutual constitution of agency within cultural discursive, economic, and embodied material structures. Understanding how HIV-positive men who have sex with men in the Philippines negotiate agency vis-a-vis wider social structures, we utilized Foucault's care of the self to locate agency in relationships with the self, others, and the broader world. Using data from narratives of 20 Filipino HIV-positive men who have sex with men, we analyzed the negotiation of agency as HIV-positive as embedded in the unique discursive terrain of Roman Catholicism and the economic materiality of a developing country. Three main processes of negotiating agency are elaborated: (1) questioning the spiritual self and the sexual body in the relationship with the self, (2) navigating interpersonal limits to care giving in the relationship with others, and (3) reclaiming human dignity in health care in the relationship with the broader world. Theoretical insights on the discursive and material constitution of healing in light of discursive and material challenges are discussed. PMID- 26851266 TI - Fast and Cheap in the Fall: Phylogenetic determinants of late flowering phenologies in Himalayan Rhododendron. AB - PREMISE OF THE STUDY: Biotic and abiotic pressures affect the beginning and end of phenologies differently, but little is known about how these temporal components may be determined by phylogeny. We tested for phylogenetic signal in the phenological components and related traits among Himalayan Rhododendron species. METHODS: We constructed a phylogeny with trnL-trnL-trnF, atpH-I, RPB2-I (3F-4R), and ITS 4-5, and examined it in combination with trait data recorded for a nine-species assemblage on Mt. Yulong, Yunnan, China. KEY RESULTS: Uniquely among phenological traits, 'last flowering day' had a significant phylogenetic signal. Last flowering day was latest in the clade with the smallest fruits. A similar association between the end of flowering and reproductive investment existed in data from Flora of China (Wu et al., 2005) for 160 Yunnan Rhododendron species, for which last flowering month was correlated with fruit size. CONCLUSIONS: Phylogenetic determinants of last flowering day and fruit size may be driven by limited time for fruit development before the onset of cold temperatures in autumn-a temporal niche that only small-fruited species can occupy. This strategy is analogous to 'fast and cheap' spring ephemerals. More may be gained from late-phenology studies, both within and among species and across seasons. PMID- 26851267 TI - Pleistocene radiation of the serpentine-adapted genus Hesperolinon and other divergence times in Linaceae (Malpighiales). AB - PREMISE OF THE STUDY: Hesperolinon (western flax; Linaceae) is endemic to the western United States, where it is notable for its high and geographically concentrated species diversity on serpentine-derived soils and for its use as a model system in disease ecology. We used a phylogenetic framework to test a long standing hypothesis that Hesperolinon is a neoendemic radiation. METHODS: Five plastid and two ribosomal nuclear DNA gene regions were sampled from 105 populations of Hesperolinon, including all 13 recently recognized species across their known ranges. We used these data to generate population-level phylogenies of Hesperolinon. We also generated a robustly sampled chronogram of Linaceae using an eight-gene, 100-taxon supermatrix calibrated using fossil Linum pollen and a published chronogram of Malpighiales. KEY RESULTS: Most diversification in Hesperolinon has taken place in the past 1-2 million yr, much more recently than previous estimates. Only the earliest-diverging species, H. drymarioides, was resolved as a clade. Denser taxon and gene sampling generally support previously proposed relationships within Linaceae, but with more recent diversification of key clades. CONCLUSIONS: Hesperolinon is an excellent example of edaphic neoendemism, in support of Raven and Axelrod's hypothesis for the genus. Dense population-level sampling reveals a complex of incipient species, with clades poorly aligned with traditional morphological circumscriptions, likely due in part to continued gene flow. The diversification of Linaceae is more recent than previously estimated, and other recent radiations (e.g., Hugonia) warrant further study. PMID- 26851268 TI - Utilizing RADseq data for phylogenetic analysis of challenging taxonomic groups: A case study in Carex sect. Racemosae. AB - PREMISE OF THE STUDY: Relationships among closely related and recently diverged taxa can be especially difficult to resolve. Here we use both Sanger sequencing and next-generation RADseq data sets to estimate phylogenetic relationships among species of Carex section Racemosae (Cyperaceae), a clade largely restricted to high latitudes and elevations. Interest in relationships among these taxa derives from questions about the species' biogeographic histories and possible links between diversification and Pleistocene glaciations. METHODS: A combination of approaches and molecular markers were used to estimate relationships among Carex species within sect. Racemosae and taxa from closely related sections. Nuclear and chloroplast loci generated by Sanger sequencing were analyzed with *BEAST, and SNP data from RADseq loci were analyzed as a concatenated data set using maximum likelihood and as independent loci using SVDquartets. KEY RESULTS: Sanger sequencing data sets resolved relationships among taxa at intermediate phylogenetic depths (albeit with low levels of support). Only the RADseq data resolved relationships with strong support at all phylogenetic depths. Moreover, different methods and data partitions of the RADseq data resulted in nearly identical topologies. Carex sect. Racemosae is a strongly supported clade, although a handful of species were found to group with closely related sections. Herbarium specimens up to 35 yr old successfully produced informative RADseq data. CONCLUSIONS: Despite the short read lengths of RADseq data, they nevertheless resolved relationships that Sanger sequencing data did not. Resolution of the phylogenetic relationships among recently and rapidly diversifying taxa within sect. Racemosae clades suggest a role for the Pleistocene glaciations in clade diversification. PMID- 26851269 TI - Estimating the Severity and Subclinical Burden of Middle East Respiratory Syndrome Coronavirus Infection in the Kingdom of Saudi Arabia. AB - Not all persons infected with Middle East respiratory syndrome coronavirus (MERS CoV) develop severe symptoms, which likely leads to an underestimation of the number of people infected and an overestimation of the severity. To estimate the number of MERS-CoV infections that have occurred in the Kingdom of Saudi Arabia, we applied a statistical model to a line list describing 721 MERS-CoV infections detected between June 7, 2012, and July 25, 2014. We estimated that 1,528 (95% confidence interval (CI): 1,327, 1,883) MERS-CoV infections occurred in this interval, which is 2.1 (95% CI: 1.8, 2.6) times the number reported. The probability of developing symptoms ranged from 11% (95% CI: 4, 25) in persons under 10 years of age to 88% (95% CI: 72, 97) in those 70 years of age or older. An estimated 22% (95% CI: 18, 25) of those infected with MERS-CoV died. MERS-CoV is deadly, but this work shows that its clinical severity differs markedly between groups and that many cases likely go undiagnosed. PMID- 26851270 TI - Stability of the Glenohumeral Joint With Combined Humeral Head and Glenoid Defects: A Cadaveric Study. AB - BACKGROUND: Shoulders with recurrent anterior instability often have combined bony defects of the humeral head and glenoid. Previous studies have looked at only isolated humeral head or glenoid defects. PURPOSE/HYPOTHESIS: The aim of this study was to define the relationship of combined humeral head and glenoid defects on anterior shoulder instability. Combined bony defects will lead to increased instability compared with an isolated defect, and the "critical" size of humeral head and glenoid defects that need to be addressed to restore stability will be smaller when combined rather than isolated. STUDY DESIGN: Controlled laboratory study. METHODS: Eighteen shoulder specimens were tested at 60 degrees of glenohumeral abduction and 80 degrees of glenohumeral external rotation. Humeral head defect sizes included 6%, 19%, 31%, and 44% of the humeral head diameter. Glenoid defect sizes included 10%, 20%, and 30% of the glenoid width. Outcome measures included percentage of intact stability ratio (%ISR; the stability ratio for a given trial divided by the stability ratio in the intact state for that specimen) and percentage of intact translation (%IT; the distance to dislocation for a given trial divided by the distance to dislocation in the intact state for that specimen). RESULTS: The decrease in %ISR reached statistical significance for humeral head defects of 44%, for glenoid defects of 30%, and for a combined 19% humeral head defect with a 20% glenoid defect (65% mean %ISR). The decrease in %IT reached statistical significance for humeral head defects >=31%, for glenoid defects >=20%, and for a combined 19% humeral head defect with a 10% glenoid defect (69% mean %IT). CONCLUSION: In shoulders with combined humeral head and glenoid defects, bony reconstruction may be indicated for humeral head defects as small as 19% of the humeral head diameter and glenoid defects as small as 10% to 20% of the glenoid width, especially if the glenoid defect produces a significant loss of glenoid concavity depth. CLINICAL RELEVANCE: In shoulders with combined humeral head and glenoid defects, bony reconstruction may be indicated for defect sizes smaller than would be indicated for either defect found in isolation. PMID- 26851271 TI - Outcomes of Combined Bone Marrow Stimulation and Patch Augmentation for Massive Rotator Cuff Tears. AB - BACKGROUND: The high failure rate after surgical repair of massive rotator cuff tears is a consistent problem. PURPOSE: To evaluate the clinical and radiological outcomes of arthroscopic rotator cuff repair with bone marrow stimulation and patch augmentation in patients with massive rotator cuff tears. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: This study included 21 patients who underwent bone marrow stimulation and patch augmentation (group 1) and 54 patients who underwent conventional repair (group 2) for massive rotator cuff tears. Postoperative clinical outcomes were evaluated based on visual analog scale (VAS) for pain, simple shoulder test (SST), University of California, Los Angeles (UCLA), Constant, and American Shoulder and Elbow Surgeons (ASES) scores at baseline, 1 year postoperatively, and final follow-up. Anatomic outcomes were evaluated by using postoperative magnetic resonance imaging at 1 year after surgery. RESULTS: No significant differences in demographic characteristics and baseline data were observed between groups 1 and 2. Clinical symptoms were significantly improved at the final follow-up in both groups (P < .001). At the final follow-up, no significant differences were found in VAS pain (P = .676), SST (P = .598), UCLA (P = .100), Constant (P = .469), or ASES (P = .880) scores. However, the retear rate was lower in group 1 (4/21, 19.0%) than in group 2 (25/54, 46.3%) (P = .036), and the medial-row failure rate (type 2 retears) was much lower in group 1 (0/4, 0%) than in group 2 (18/25, 72.0%) (P = .014). CONCLUSION: Concomitant bone marrow stimulation and patch augmentation significantly reduced retear and medial-row failure rates in the arthroscopic repair of massive rotator cuff tears. PMID- 26851272 TI - Recovery of Muscle Strength After Intact Arthroscopic Rotator Cuff Repair According to Preoperative Rotator Cuff Tear Size. AB - BACKGROUND: The recovery of muscle strength after arthroscopic rotator cuff repair based on the preoperative tear size has not yet been well described. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate the recovery period of muscle strength by a serial assessment of isometric strength after arthroscopic rotator cuff repair based on the preoperative tear size. The hypothesis was that muscle strength in patients with small and medium tears would recover faster than that in those with large-to-massive tears. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 164 patients who underwent arthroscopic rotator cuff repair were included. Isometric strength in forward flexion (FF), internal rotation (IR), and external rotation (ER) was evaluated preoperatively and at 6, 12, 18, and 24 months after surgery. Preoperative magnetic resonance imaging scans were assessed to evaluate the quality of the rotator cuff muscle, including fatty infiltration, occupation ratio, and tangent sign. Patient satisfaction as well as visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES), and Constant scores were assessed at every follow-up. RESULTS: Muscle strength demonstrated the slowest recovery in pain relief and the restoration of shoulder function. To reach the strength of the uninjured contralateral shoulder in all 3 planes of motion, recovery took 6 months in patients with small tears and 18 months in patients with medium tears. Patients with large-to-massive tears showed continuous improvement in strength up to 18 months; however, they did not reach the strength of the contralateral shoulder at final follow-up. At final follow up, mean strength in FF, IR, and ER was 113.0%, 118.0%, and 112.6% of the contralateral shoulder in patients with small tears, respectively; 105.0%, 112.1%, and 102.6% in patients with medium tears, respectively; and 87.6%, 89.5%, and 85.2% in patients with large-to-massive tears, respectively. Muscle strength in any direction did not significantly correlate with postoperative patient satisfaction (P = .374, .515, and .692 for FF, IR, and ER, respectively), whereas it highly correlated with preoperative quality of the muscle. CONCLUSION: The recovery of muscle strength after arthroscopic repair was poorly correlated with patient satisfaction. This study recommends that regardless of pain relief and improved shoulder function, patients with larger than medium tears should be encouraged to continue with rehabilitation for the maximal restoration of muscle strength beyond 1 year postoperatively. PMID- 26851273 TI - Antibiotics: from prehistory to the present day. AB - Antimicrobials have been in use for many thousands of years in a variety of formats. In this article, I trace how we have moved from ingenious use of agents available in the environment to chemically engineered agents. PMID- 26851274 TI - Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis. AB - OBJECTIVES: Notch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice. METHODS: Notch and hedgehog signalling were analysed by real time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and uCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments. RESULTS: Notch signalling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1. CONCLUSIONS: Inhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA. PMID- 26851275 TI - Insights into Coupled Folding and Binding Mechanisms from Kinetic Studies. AB - Intrinsically disordered proteins (IDPs) are characterized by a lack of persistent structure. Since their identification more than a decade ago, many questions regarding their functional relevance and interaction mechanisms remain unanswered. Although most experiments have taken equilibrium and structural perspectives, fewer studies have investigated the kinetics of their interactions. Here we review and highlight the type of information that can be gained from kinetic studies. In particular, we show how kinetic studies of coupled folding and binding reactions, an important class of signaling event, are needed to determine mechanisms. PMID- 26851276 TI - Thumb Site 2 Inhibitors of Hepatitis C Viral RNA-dependent RNA Polymerase Allosterically Block the Transition from Initiation to Elongation. AB - Replication of the hepatitis C viral genome is catalyzed by the NS5B (nonstructural protein 5B) RNA-dependent RNA polymerase, which is a major target of antiviral drugs currently in the clinic. Prior studies established that initiation of RNA replication could be facilitated by starting with a dinucleotide (pGG). Here we establish conditions for efficient initiation from GTP to form the dinucleotide and subsequent intermediates leading to highly processive elongation, and we examined the effects of four classes of nonnucleoside inhibitors on each step of the reaction. We show that palm site inhibitors block initiation starting from GTP but not when starting from pGG. In addition we show that nonnucleoside inhibitors binding to thumb site-2 (NNI2) lead to the accumulation of abortive intermediates three-five nucleotides in length. Our kinetic analysis shows that NNI2 do not significantly block initiation or elongation of RNA synthesis; rather, they block the transition from initiation to elongation, which is thought to proceed with significant structural rearrangement of the enzyme-RNA complex including displacement of the beta-loop from the active site. Direct measurement in single turnover kinetic studies show that pyrophosphate release is faster than the chemistry step, which appears to be rate-limiting during processive synthesis. These results reveal important new details to define the steps involved in initiation and elongation during viral RNA replication, establish the allosteric mechanisms by which NNI2 inhibitors act, and point the way to the design of more effective allosteric inhibitors that exploit this new information. PMID- 26851277 TI - Design Principles Involving Protein Disorder Facilitate Specific Substrate Selection and Degradation by the Ubiquitin-Proteasome System. AB - The ubiquitin-proteasome system (UPS) regulates diverse cellular pathways by the timely removal (or processing) of proteins. Here we review the role of structural disorder and conformational flexibility in the different aspects of degradation. First, we discuss post-translational modifications within disordered regions that regulate E3 ligase localization, conformation, and enzymatic activity, and also the role of flexible linkers in mediating ubiquitin transfer and reaction processivity. Next we review well studied substrates and discuss that substrate elements (degrons) recognized by E3 ligases are highly disordered: short linear motifs recognized by many E3s constitute an important class of degrons, and these are almost always present in disordered regions. Substrate lysines targeted for ubiquitination are also often located in neighboring regions of the E3 docking motifs and are therefore part of the disordered segment. Finally, biochemical experiments and predictions show that initiation of degradation at the 26S proteasome requires a partially unfolded region to facilitate substrate entry into the proteasomal core. PMID- 26851278 TI - Role of Intrinsic Protein Disorder in the Function and Interactions of the Transcriptional Coactivators CREB-binding Protein (CBP) and p300. AB - The transcriptional coactivators CREB-binding protein (CBP) and p300 undergo a particularly rich set of interactions with disordered and partly ordered partners, as a part of their ubiquitous role in facilitating transcription of genes. CBP and p300 contain a number of small structured domains that provide scaffolds for the interaction of disordered transactivation domains from a wide variety of partners, including p53, hypoxia-inducible factor 1alpha (HIF-1alpha), NF-kappaB, and STAT proteins, and are the targets for the interactions of disordered viral proteins that compete with cellular factors to disrupt signaling and subvert the cell cycle. The functional diversity of the CBP/p300 interactome provides an excellent example of the power of intrinsic disorder to facilitate the complexity of living systems. PMID- 26851280 TI - Targeting Stereotyped B Cell Receptors from Chronic Lymphocytic Leukemia Patients with Synthetic Antigen Surrogates. AB - Chronic lymphocytic leukemia (CLL) is a disease in which a single B-cell clone proliferates relentlessly in peripheral lymphoid organs, bone marrow, and blood. DNA sequencing experiments have shown that about 30% of CLL patients have stereotyped antigen-specific B-cell receptors (BCRs) with a high level of sequence homology in the variable domains of the heavy and light chains. These include many of the most aggressive cases that haveIGHV-unmutated BCRs whose sequences have not diverged significantly from the germ line. This suggests a personalized therapy strategy in which a toxin or immune effector function is delivered selectively to the pathogenic B-cells but not to healthy B-cells. To execute this strategy, serum-stable, drug-like compounds able to target the antigen-binding sites of most or all patients in a stereotyped subset are required. We demonstrate here the feasibility of this approach with the discovery of selective, high affinity ligands for CLL BCRs of the aggressive, stereotyped subset 7P that cross-react with the BCRs of several CLL patients in subset 7p, but not with BCRs from patients outside this subset. PMID- 26851279 TI - Modulation of Intrinsically Disordered Protein Function by Post-translational Modifications. AB - Post-translational modifications (PTMs) produce significant changes in the structural properties of intrinsically disordered proteins (IDPs) by affecting their energy landscapes. PTMs can induce a range of effects, from local stabilization or destabilization of transient secondary structure to global disorder-to-order transitions, potentially driving complete state changes between intrinsically disordered and folded states or dispersed monomeric and phase separated states. Here, we discuss diverse biological processes that are dependent on PTM regulation of IDPs. We also present recent tools for generating homogenously modified IDPs for studies of PTM-mediated IDP regulatory mechanisms. PMID- 26851282 TI - Expanding the Range of Protein Function at the Far End of the Order-Structure Continuum. AB - The traditional view of the structure-function paradigm is that a protein's function is inextricably linked to a well defined, three-dimensional structure, which is determined by the protein's primary amino acid sequence. However, it is now accepted that a number of proteins do not adopt a unique tertiary structure in solution and that some degree of disorder is required for many proteins to perform their prescribed functions. In this review, we highlight how a number of protein functions are facilitated by intrinsic disorder and introduce a new protein structure taxonomy that is based on quantifiable metrics of a protein's disorder. PMID- 26851284 TI - Introduction to the Thematic Minireview Series on Intrinsically Disordered Proteins. AB - In this thematic minireview series, the JBC presents six exciting articles on low complexity or intrinsically disordered proteins (IDPs). The dynamical and fluctuating structures of IDPs or of disordered regions within proteins result in virtually all of their primary sequence being exposed, at least at some time, to potential interacting partners. Their structural versatility underlies their often wide functional repertoires, which is further expanded by post translational modifications. Given these characteristics, it is not surprising that IDPs serve as important hubs in signaling networks, scaffolding multivalent interactions. They are also important for organizing membrane-less protein organelles. This collection of reviews discusses biophysical approaches for studying IDPs and illuminates their importance to critical functions such as cell cycle control, transcription, and translation, as well as their regulation via cellular input signals. PMID- 26851281 TI - A G Protein-biased Designer G Protein-coupled Receptor Useful for Studying the Physiological Relevance of Gq/11-dependent Signaling Pathways. AB - Designerreceptorsexclusivelyactivated by adesignerdrug (DREADDs) are clozapine-N oxide-sensitive designer G protein-coupled receptors (GPCRs) that have emerged as powerful novel chemogenetic tools to study the physiological relevance of GPCR signaling pathways in specific cell types or tissues. Like endogenous GPCRs, clozapine-N-oxide-activated DREADDs do not only activate heterotrimeric G proteins but can also trigger beta-arrestin-dependent (G protein-independent) signaling. To dissect the relative physiological relevance of G protein mediatedversusbeta-arrestin-mediated signaling in different cell types or physiological processes, the availability of G protein- and beta-arrestin-biased DREADDs would be highly desirable. In this study, we report the development of a mutationally modified version of a non-biased DREADD derived from the M3muscarinic receptor that can activate Gq/11with high efficacy but lacks the ability to interact with beta-arrestins. We also demonstrate that this novel DREADD is activein vivoand that cell type-selective expression of this new designer receptor can provide novel insights into the physiological roles of G protein (Gq/11)-dependentversusbeta-arrestin-dependent signaling in hepatocytes. Thus, this novel Gq/11-biased DREADD represents a powerful new tool to study the physiological relevance of Gq/11-dependent signaling in distinct tissues and cell types, in the absence of beta-arrestin-mediated cellular effects. Such studies should guide the development of novel classes of functionally biased ligands that show high efficacy in various pathophysiological conditions but display a reduced incidence of side effects. PMID- 26851283 TI - The Type IV Pilus Assembly ATPase PilB of Myxococcus xanthus Interacts with the Inner Membrane Platform Protein PilC and the Nucleotide-binding Protein PilM. AB - Type IV pili (T4P) are ubiquitous bacterial cell surface structures, involved in processes such as twitching motility, biofilm formation, bacteriophage infection, surface attachment, virulence, and natural transformation. T4P are assembled by machinery that can be divided into the outer membrane pore complex, the alignment complex that connects components in the inner and outer membrane, and the motor complex in the inner membrane and cytoplasm. Here, we characterize the inner membrane platform protein PilC, the cytosolic assembly ATPase PilB of the motor complex, and the cytosolic nucleotide-binding protein PilM of the alignment complex of the T4P machinery ofMyxococcus xanthus PilC was purified as a dimer and reconstituted into liposomes. PilB was isolated as a monomer and bound ATP in a non-cooperative manner, but PilB fused to Hcp1 ofPseudomonas aeruginosaformed a hexamer and bound ATP in a cooperative manner. Hexameric but not monomeric PilB bound to PilC reconstituted in liposomes, and this binding stimulated PilB ATPase activity. PilM could only be purified when it was stabilized by a fusion with a peptide corresponding to the first 16 amino acids of PilN, supporting an interaction between PilM and PilN(1-16). PilM-N(1-16) was isolated as a monomer that bound but did not hydrolyze ATP. PilM interacted directly with PilB, but only with PilC in the presence of PilB, suggesting an indirect interaction. We propose that PilB interacts with PilC and with PilM, thus establishing the connection between the alignment and the motor complex. PMID- 26851285 TI - Acetylation of p53 Protein at Lysine 120 Up-regulates Apaf-1 Protein and Sensitizes the Mitochondrial Apoptotic Pathway. AB - The p53 tumor suppressor controls cell growth, metabolism, and death by regulating the transcription of various target genes. The target-specific transcriptional activity of p53 is highly regulated. Here we demonstrate that acetylation of p53 at Lys-120 up-regulates its transcriptional activity toward Apaf-1, a core component in the mitochondrial apoptotic pathway, and thus sensitizes caspase activation and apoptosis. We found that histone deacetylase (HDAC) inhibitors, including butyrate, augment Lys-120 acetylation of p53 and thus Apaf-1 expression by inhibiting HDAC1. In p53-null cells, transfection of wild-type but not K120R mutant p53 can restore the p53-dependent sensitivity to butyrate. Strikingly, transfection of acetylation-mimicking K120Q mutant p53 is sufficient to up-regulates Apaf-1 in a manner independent of butyrate treatment. Therefore, HDAC inhibitors can induce p53 acetylation at lysine 120, which in turn enhances mitochondrion-mediated apoptosis through transcriptional up regulation of Apaf-1. PMID- 26851287 TI - Fracture clinic redesign reduces the cost of outpatient orthopaedic trauma care. AB - OBJECTIVES: "Virtual fracture clinics" have been reported as a safe and effective alternative to the traditional fracture clinic. Robust protocols are used to identify cases that do not require further review, with the remainder triaged to the most appropriate subspecialist at the optimum time for review. The objective of this study was to perform a "top-down" analysis of the cost effectiveness of this virtual fracture clinic pathway. METHODS: National Health Service financial returns relating to our institution were examined for the time period 2009 to 2014 which spanned the service redesign. RESULTS: The total staffing costs rose by 4% over the time period (from L1 744 933 to L1 811 301) compared with a national increase of 16%. The total outpatient department rate of attendance fell by 15% compared with a national fall of 5%. Had our local costs increased in line with the national average, an excess expenditure of L212 705 would have been required for staffing costs. CONCLUSIONS: The virtual fracture clinic system was associated with less overall use of staff resources in comparison to national cost data. Adoption of this system nationally may have the potential to achieve significant cost savings.Cite this article: P. J. Jenkins. Fracture clinic redesign reduces the cost of outpatient orthopaedic trauma care. Bone Joint Res 2016;5:33-36. doi: 10.1302/2046-3758.52.2000506. PMID- 26851288 TI - Low chronic workload and the acute:chronic workload ratio are more predictive of injury than between-match recovery time: a two-season prospective cohort study in elite rugby league players. AB - BACKGROUND: Between-match recovery time, and acute and chronic workloads likely affect subsequent match-injury risk in elite rugby league players. METHODS: Workloads of 28 players throughout two seasons were calculated during short (<7 days), and long (>=7 days) between-match recovery times. 'Acute' workloads (1 week) greater than 'chronic' workloads (4-week rolling average acute workload) resulted in acute:chronic workload ratios above 1. RESULTS: No difference was found between the match-injury risk of short and long between-match recovery periods (7.5+/-2.5% vs 6.8+/-2.5%). When players had a short recovery between matches, high chronic workloads (18.9-22.0 km) were associated with a smaller risk of match injury than chronic workloads <18.9 km (relative risk (RR) range 0.27-0.32 (CI 0.08 to 0.92); likelihood range 90-95%, likely). Players who had shorter recovery and acute:chronic workload ratios >=1.6, were 3.4-5.8 times likely to sustain a match injury than players with lower acute:chronic workload ratios (RR range 3.41-5.80 (CI 1.17 to 19.2); likelihood range 96-99%, very likely). Acute:chronic workload ratios between 1.2 and 1.6 during short between match recovery times demonstrated a greater risk of match injury than ratios between 1.0 and 1.2 (RR=2.88 (CI 0.97 to 8.55); likelihood=92%, likely). CONCLUSIONS: Contrary to the philosophy that high workloads and shorter recovery equate to increased injury risk, our data suggest that high and very-high chronic workloads may protect against match injury following shorter between-match recovery periods. Acute:chronic workload ratios ~1.5 are associated with a greater risk of match injury than lower acute:chonic workload ratios. Importantly, workloads can be manipulated to decrease the match-injury risk associated with shorter recovery time between matches. PMID- 26851286 TI - Dancing Protein Clouds: The Strange Biology and Chaotic Physics of Intrinsically Disordered Proteins. AB - Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally heterogeneous, and can be considered an important part of the structure-function continuum. Furthermore, IDPs/IDPRs are everywhere, and are ubiquitously engaged in various interactions characterized by a wide spectrum of binding scenarios and an even wider spectrum of structural and functional outputs. PMID- 26851289 TI - CPR 11: a mobile application that can help in saving lives (Mobile App User Guide). PMID- 26851291 TI - Emerging roles for hemostatic dysfunction in malaria pathogenesis. AB - Severe Plasmodium falciparum malaria remains a leading cause of mortality, particularly in sub-Saharan Africa where it accounts for up to 1 million deaths per annum. In spite of the significant mortality and morbidity associated with cerebral malaria (CM), the molecular mechanisms involved in the pathophysiology of severe malaria remain surprisingly poorly understood. Previous studies have demonstrated that sequestration of P falciparum-infected erythrocytes within the microvasculature of the brain plays a key role in the development of CM. In addition, there is convincing evidence that both endothelial cell activation and platelets play critical roles in the modulating the pathogenesis of severe P falciparum malaria. In this review, we provide an overview of recent studies that have identified novel roles through which hemostatic dysfunction may directly influence malaria pathogenesis. In particular, we focus on emerging data suggesting that von Willebrand factor, coagulation cascade activation, and dysfunction of the protein C pathway may be of specific importance in this context. These collective insights underscore a growing appreciation of the important, but poorly understood, role of hemostatic dysfunction in malaria progression and, importantly, illuminate potential approaches for novel therapeutic strategies. Given that the mortality rate associated with CM remains on the order of 20% despite the availability of effective antimalarial therapy, development of adjunctive therapies that can attenuate CM progression clearly represents a major unmet need. These emerging data are thus not only of basic scientific interest, but also of direct clinical significance. PMID- 26851290 TI - Effects and dose-response relationships of resistance training on physical performance in youth athletes: a systematic review and meta-analysis. AB - OBJECTIVES: To quantify age, sex, sport and training type-specific effects of resistance training on physical performance, and to characterise dose-response relationships of resistance training parameters that could maximise gains in physical performance in youth athletes. DESIGN: Systematic review and meta analysis of intervention studies. DATA SOURCES: Studies were identified by systematic literature search in the databases PubMed and Web of Science (1985 2015). Weighted mean standardised mean differences (SMDwm) were calculated using random-effects models. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Only studies with an active control group were included if these investigated the effects of resistance training in youth athletes (6-18 years) and tested at least one physical performance measure. RESULTS: 43 studies met the inclusion criteria. Our analyses revealed moderate effects of resistance training on muscle strength and vertical jump performance (SMDwm 0.8-1.09), and small effects on linear sprint, agility and sport-specific performance (SMDwm 0.58-0.75). Effects were moderated by sex and resistance training type. Independently computed dose-response relationships for resistance training parameters revealed that a training period of >23 weeks, 5 sets/exercise, 6-8 repetitions/set, a training intensity of 80 89% of 1 repetition maximum (RM), and 3-4 min rest between sets were most effective to improve muscle strength (SMDwm 2.09-3.40). SUMMARY/CONCLUSIONS: Resistance training is an effective method to enhance muscle strength and jump performance in youth athletes, moderated by sex and resistance training type. Dose-response relationships for key training parameters indicate that youth coaches should primarily implement resistance training programmes with fewer repetitions and higher intensities to improve physical performance measures of youth athletes. PMID- 26851292 TI - Long-term treatment follow-up of children with sickle cell disease monitored with abnormal transcranial Doppler velocities. AB - Stroke risk in sickle cell anemia (SCA), predicted by high transcranial Doppler (TCD) velocities, is prevented by transfusions. We present the long-term follow up of SCA children from the Creteil newborn cohort (1992-2012) detected at risk by TCD and placed on chronic transfusions. Patients with normalized velocities and no stenosis were treated with hydroxyurea, known to decrease anemia and hemolytic rate. Trimestrial Doppler was performed and transfusions restarted immediately in the case of reversion to abnormal velocities. Patients with a genoidentical donor underwent transplant. Abnormal time-averaged maximum mean velocities (TAMMV) >=200 cm/s were detected in 92 SCA children at a mean age of 3.7 years (range, 1.3-8.3 years). No stroke occurred posttransfusion after a mean follow-up of 6.1 years. Normalization of velocities (TAMMV < 170 cm/s) was observed in 83.5% of patients. Stenosis, present in 27.5% of patients, was associated with the risk of non-normalization (P< .001). Switch from transfusions to hydroxyurea was prescribed for 45 patients, with a mean follow-up of 3.4 years. Reversion, predicted by baseline reticulocyte count >=400 * 10(9)/L (P< .001), occurred in 28.9% (13/45) patients at the mean age of 7.1 years (range, 4.3-9.5 years). Transplant, performed in 24 patients, allowed transfusions to be safely stopped in all patients and velocities to be normalized in 4 patients who still had abnormal velocities on transfusions. This long-term cohort study shows that transfusions can be stopped not only in transplanted patients but also in a subset of patients switched to hydroxyurea, provided trimestrial Doppler follow up and immediate restart of transfusions in the case of reversion. PMID- 26851294 TI - Better training is needed on fetal alcohol disorders, says BMA. PMID- 26851295 TI - The Emerging Importance of IgG Fab Glycosylation in Immunity. AB - Human IgG is the most abundant glycoprotein in serum and is crucial for protective immunity. In addition to conserved IgG Fc glycans, ~15-25% of serum IgG contains glycans within the variable domains. These so-called "Fab glycans" are primarily highly processed complex-type biantennary N-glycans linked to N glycosylation sites that emerge during somatic hypermutation. Specific patterns of Fab glycosylation are concurrent with physiological and pathological conditions, such as pregnancy and rheumatoid arthritis. With respect to function, Fab glycosylation can significantly affect stability, half-life, and binding characteristics of Abs and BCRs. Moreover, Fab glycans are associated with the anti-inflammatory activity of IVIgs. Consequently, IgG Fab glycosylation appears to be an important, yet poorly understood, process that modulates immunity. PMID- 26851296 TI - A Review of the McMorran Diet for Rearing Lepidoptera Species With Addition of a Further 39 Species. AB - Research on cutworms led us to explore the use of the McMorran diet to rear lepidopteran species, mainly Noctuidae, under laboratory conditions. We documented the development of 103 lepidopteran species, including 39 species not previously reported in the literature, to be reared on this diet. Given its low cost, ease of preparation, and wide species' acceptance, this diet provides a powerful tool for facilitating Lepidoptera and other insects rearing and research in the laboratory. PMID- 26851293 TI - The NAE inhibitor pevonedistat interacts with the HDAC inhibitor belinostat to target AML cells by disrupting the DDR. AB - Two classes of novel agents, NEDD8-activating enzyme (NAE) and histone deacetylase (HDAC) inhibitors, have shown single-agent activity in acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS). Here we examined mechanisms underlying interactions between the NAE inhibitor pevonedistat (MLN4924) and the approved HDAC inhibitor belinostat in AML/MDS cells. MLN4924/belinostat coadministration synergistically induced AML cell apoptosis with or without p53 deficiency or FLT3-internal tandem duplication (ITD), whereas p53 short hairpin RNA (shRNA) knockdown or enforced FLT3-ITD expression significantly sensitized cells to the regimen. MLN4924 blocked belinostat-induced antiapoptotic gene expression through nuclear factor-kappaB inactivation. Each agent upregulated Bim, and Bim knockdown significantly attenuated apoptosis. Microarrays revealed distinct DNA damage response (DDR) genetic profiles between individual vs combined MLN4924/belinostat exposure. Whereas belinostat abrogated the MLN4924-activated intra-S checkpoint through Chk1 and Wee1 inhibition/downregulation, cotreatment downregulated multiple homologous recombination and nonhomologous end-joining repair proteins, triggering robust double-stranded breaks, chromatin pulverization, and apoptosis. Consistently, Chk1 or Wee1 shRNA knockdown significantly sensitized AML cells to MLN4924. MLN4924/belinostat displayed activity against primary AML or MDS cells, including those carrying next-generation sequencing-defined poor-prognostic cancer hotspot mutations, and CD34(+)/CD38(-)/CD123(+) populations, but not normal CD34(+) progenitors. Finally, combined treatment markedly reduced tumor burden and significantly prolonged animal survival (P < .0001) in AML xenograft models with negligible toxicity, accompanied by pharmacodynamic effects observed in vitro. Collectively, these findings argue that MLN4924 and belinostat interact synergistically by reciprocally disabling the DDR in AML/MDS cells. This strategy warrants further consideration in AML/MDS, particularly in disease with unfavorable genetic aberrations. PMID- 26851297 TI - Feasibility and safety comparison of laparoscopy-assisted versus open gastrectomy for advanced gastric carcinoma with D2 lymphadenectomy. AB - OBJECTIVE: Laparoscopy-assisted gastrectomy for advanced gastric cancer still remains controversial. The aim of this study is to compare oncologic feasibility and technical safety of laparoscopic versus open gastrectomy for advanced gastric cancer with D2 lymphadenectomy by comparing patients' short-term postoperative outcomes. METHODS: One hundred and one patients with laparoscopy-assisted gastrectomy and 101 patients with open gastrectomy were one-to-one matched and then compared in terms of operative outcomes and hospital courses. RESULTS: The laparoscopic group showed significantly longer operating time (297.4 vs. 198.1 min, P < 0.001), earlier first flatus time (2.8 vs. 3.6 days, P < 0.001), earlier diet start time (3.8 vs. 4.6 days, P < 0.001), shorter hospital stay (10.5 vs. 11.9 days, P < 0.001) and less morbidity (21.8 vs. 37.6%, P = 0.019). However, retrieval lymph nodes, intraoperative blood loss, transfused patients, postoperative fever and mortality were similar in the two groups. As for complications, incision infection (1.0 vs. 8.9%, P = 0.021) was significantly more common in the open group than in the laparoscopic group. In the subgroup comparisons of outcomes of laparoscopy-assisted gastrectomy, the tumor, node, metastasis III group showed significantly increased retrieval lymph nodes (37.2 vs. 31.0, P < 0.001), increased intraoperative blood loss (147.2 vs. 120.5 ml, P = 0.010), increased length of hospital stay (11.1 vs. 9.9 days, P < 0.001) and increased morbidity (32.6 vs. 13.8%, P = 0.024) when compared with the tumor, node, metastasis II group. CONCLUSIONS: Laparoscopy-assisted gastrectomy is feasible and safe for the treatment of advanced gastric cancer with D2 lymphadenectomy compared with open gastrectomy. Higher-level tumor stage (tumor, node, metastasis III) may increase the operative risk and should be performed with caution by surgeons with considerable experience of laparoscopic gastrectomy. PMID- 26851299 TI - Nuclear compartmentalization of serine racemase regulates d-serine production. IMPLICATIONS FOR N-METHYL-d-ASPARTATE (NMDA) RECEPTOR ACTIVATION. PMID- 26851298 TI - S-nitrosylation of fatty acid synthase regulates its activity through dimerization. AB - NO regulates a variety of physiological processes, including cell proliferation, differentiation, and inflammation. S-nitrosylation, a NO-mediated reversible protein modification, leads to changes in the activity and function of proteins. In particular, the role of S-nitrosylation during adipogenesis is largely unknown. We hypothesized that the normal physiological levels of NO, but not the excess levels generated under severe conditions, such as inflammation, may be critically involved in the proper regulation of adipogenesis. We found that endogenous S-nitrosylation of proteins was required for adipocyte differentiation. By performing a biotin-switch assay, we identified FAS, a key lipogenic enzyme in adipocytes, as a target of S-nitrosylation during adipogenesis. Interestingly, we also observed that the dimerization of FAS increased in parallel with the amount of S-nitrosylated FAS during adipogenesis. In addition, we found that exogenous NO enhanced the dimerization and the enzymatic activity of FAS. Moreover, site-directed mutagenesis of three predicted S-nitrosylation sites indicated that S-nitrosylation of FAS at Cys(1471)and Cys(2091), but not at Cys(1127), increased its enzymatic activity. Taken together, these results suggest that the S-nitrosylation of FAS at normal physiological levels of NO increases its activity through dimerization and may contribute to the proper regulation of adipogenesis. PMID- 26851300 TI - Characterization of the product of a nonribosomal peptide synthetase-like (NRPS like) gene using the doxycycline dependent Tet-on system in Aspergillus terreus. AB - Genome sequencing of the fungus Aspergillus terreus uncovered a number of silent core structural biosynthetic genes encoding enzymes presumed to be involved in the production of cryptic secondary metabolites. There are five nonribosomal peptide synthetase (NRPS)-like genes with the predicted A-T-TE domain architecture within the A. terreus genome. Among the five genes, only the product of pgnA remains unknown. The Tet-on system is an inducible, tunable and metabolism-independent expression system originally developed for Aspergillus niger. Here we report the adoption of the Tet-on system as an effective gene activation tool in A. terreus. Application of this system in A. terreus allowed us to uncover the product of the cryptic NRPS-like gene, pgnA. Furthermore expression of pgnA in the heterologous Aspergillus nidulans host suggested that the pgnA gene alone is necessary for phenguignardic acid (1) biosynthesis. PMID- 26851301 TI - State of the ASE. PMID- 26851302 TI - Working to Prevent Work-related Musculoskeletal Disorders. PMID- 26851303 TI - Perspective: Incorporating Vascular Ultrasound into an Adult Echocardiography Laboratory--Practical Considerations. PMID- 26851304 TI - Production of specific-molecular-weight hyaluronan by metabolically engineered Bacillus subtilis 168. AB - Low-molecular-weight hyaluronan (LMW-HA) has attracted much attention because of its many potential applications. Here, we efficiently produced specific LMW-HAs from sucrose in Bacillus subtilis. By coexpressing the identified committed genes (tuaD, gtaB, glmU, glmM, and glmS) and downregulating the glycolytic pathway, HA production was significantly increased from 1.01gL(-1) to 3.16gL(-1), with a molecular weight range of 1.40*10(6)-1.83*10(6)Da. When leech hyaluronidase was actively expressed after N-terminal engineering (1.62*10(6)UmL(-1)), the production of HA was substantially increased from 5.96gL(-1) to 19.38gL(-1). The level of hyaluronidase was rationally regulated with a ribosome-binding site engineering strategy, allowing the production of LMW-HAs with a molecular weight range of 2.20*10(3)-1.42*10(6)Da. Our results confirm that this strategy for the controllable expression of hyaluronidase, together with the optimization of the HA synthetic pathway, effectively produces specific LMW-HAs, and could also be used to produce other LMW polysaccharides. PMID- 26851306 TI - Sex and stress steroids in adolescence: Gonadal regulation of the hypothalamic pituitary-adrenal axis in the rat. AB - This review provides an overview of the current understanding of the role of the hypothalamic-pituitary-gonadal (HPG) axis in regulating the hypothalamic pituitary-adrenal (HPA) axis response to stressors. HPA function is influenced by both organizational (programming) and activational effects of gonadal hormones. Typically, in adult rats, estradiol increases and androgens decrease the HPA response to stressors, thereby contributing to sex differences in HPA function, and sensitivity of the HPA axis to gonadal steroids is in part determined by exposure to these hormones in early development. Although developmental differences in HPA function are well characterized, the extent to which gonadal steroids contribute to age differences in HPA function is not well understood. Deficits in the understanding of the relationships between the HPA and HPG axes are greatest for the adolescent period of development. The critical outstanding questions are, when do gonadal hormones begin to regulate HPA function in adolescence, and what mechanisms precipitate change in sensitivity of the HPA axis to the HPG axis at this stage of life. PMID- 26851305 TI - Dietary fatty acid composition affects food intake and gut-brain satiety signaling in Senegalese sole (Solea senegalensis, Kaup 1858) larvae and post larvae. AB - Little is known how dietary lipids affect food intake during larval development of fish, especially with regard to fatty acid (FA) composition. In fact, very little work has been done on appetite regulation and food intake in fish larvae in general, due to biological and technical difficulties associated with this type of studies. A new method using fluorescent microspheres as markers was developed in this study to evaluate food intake and prey selectivity of Senegalese sole larvae and post-larvae. Food intake was quantified in fish fed Artemia metanauplii enriched with oils differing in FA profile: cod liver oil (CLO), linseed oil (LSO), soybean oil (SBO) or olive oil (OO). The fish did not preferentially ingest a specific diet when presented with a choice. However, pre metamorphic larvae from the CLO treatment ingested more metanauplii per g body weight, while differences in post-larvae were not significant. These findings were developed further by analyzing mRNA levels of a range of putative anorexigenic (pyya, pyyb, glp1, cckl, cart1a, cart1b, cart2a, cart4, pomca, pomcb, crf) and orexigenic (gal, npy, agrp2) genes, to identify those which are significantly affected by feeding and/or dietary FA composition. The variety of expression patterns observed highlighted the complexity of appetite regulatory mechanisms. In general, fish fed the CLO diet tended to show gene expression patterns most dissimilar to the remaining treatments. Expression in pre metamorphic larvae was generally less in accordance with the putative function of the genes than in post-larvae, which could suggest a yet underdeveloped regulatory system. PMID- 26851307 TI - Optical detection of neuron connectivity by random access two-photon microscopy. AB - BACKGROUND: Knowledge about the distribution, strength, and direction of synaptic connections within neuronal networks are crucial for understanding brain function. Electrophysiology using multiple electrodes provides a very high temporal resolution, but does not yield sufficient spatial information for resolving neuronal connection topology. Optical recording techniques using single cell resolution have provided promise for providing spatial information. Although calcium imaging from hundreds of neurons has provided a novel view of the neural connections within the network, the kinetics of calcium responses are not fast enough to resolve each action potential event with high fidelity. Therefore, it is not possible to detect the direction of neuronal connections. NEW METHOD: We took advantage of the fast kinetics and large dynamic range of the DiO/DPA combination of voltage sensitive dye and the fast scan speed of a custom-made random-access two-photon microscope to resolve each action potential event from multiple neurons in culture. RESULTS: Long-duration recording up to 100min from cultured hippocampal neurons yielded sufficient numbers of spike events for analyzing synaptic connections. Cross-correlation analysis of neuron pairs clearly distinguished synaptically connected neuron pairs with the connection direction. COMPARISON WITH EXISTING METHOD: The long duration recording of action potentials with voltage-sensitive dye utilized in the present study is much longer than in previous studies. Simultaneous optical voltage and calcium measurements revealed that voltage-sensitive dye is able to detect firing events more reliably than calcium indicators. CONCLUSIONS: This novel method reveals a new view of the functional structure of neuronal networks. PMID- 26851308 TI - Phenotypic, genotypic, and functional characterization of normal and acute myeloid leukemia-derived marrow endothelial cells. AB - In addition to participation in homing, egress, and transmigration of hematopoietic cells, marrow endothelium also contributes to cell proliferation and survival. Endothelial cells from multiple vascular beds are able to prevent spontaneous or therapy-induced apoptosis in acute myelogenous leukemia (AML) blasts. Marrow-derived endothelial cells from leukemia patients have not been well-characterized, and in this work, endothelial cells were purified from marrow aspirates from normal subjects or from newly diagnosed AML patients to compare these cells phenotypically and functionally. By reverse transcription polymerase chain reaction, these cells express CD31, Tie-2, vascular endothelial growth factor (VEGF), and endothelial nitric oxide synthase (eNOS), supporting endothelial origin. They take up acetyl low-density lipoprotein and are able to form tubular structures. Culture of AML cells with endothelial cells from both normal and AML subjects supported adhesion, transmigration, and leukemia colony forming unit outgrowth. RNA-sequencing analysis revealed 130 genes significantly up- or downregulated in AML-derived endothelial cells as compared with those derived from normal marrow. The genes differentially expressed (p < 0.001) were included in biological function categories involving cancer, cell development, cell growth and proliferation, cell signaling, inflammatory response, and cell death and survival. Further pathway analysis revealed upregulation of c-Fos and genes involved in chemotaxis such as CXCL16. AML-derived endothelial cells are similar in phenotype and function to their normal marrow-derived counterparts, but genomic analysis suggests a differential signature with altered expression of genes, which could play a role in leukemogenesis or leukemia cell maintenance in the marrow microenvironment. PMID- 26851309 TI - Distinct hemispheric specializations for native and non-native languages in one day-old newborns identified by fNIRS. AB - This study assessed whether the neonatal brain recruits different neural networks for native and non-native languages at birth. Twenty-seven one-day-old full-term infants underwent functional near-infrared spectroscopy (fNIRS) recording during linguistic and non-linguistic stimulation. Fourteen newborns listened to linguistic stimuli (native and non-native language stories) and 13 newborns were exposed to non-linguistic conditions (native and non-native stimuli played in reverse). Comparisons between left and right hemisphere oxyhemoglobin (HbO2) concentration changes over the temporal areas revealed clear left hemisphere dominance for native language, whereas non-native stimuli were associated with right hemisphere lateralization. In addition, bilateral cerebral activation was found for non-linguistic stimulus processing. Overall, our findings indicate that from the first day after birth, native language and prosodic features are processed in parallel by distinct neural networks. PMID- 26851310 TI - Risk Factors for Free Flap Failure in 2,846 Patients With Head and Neck Cancer: A National Database Study in Japan. AB - PURPOSE: The risk factors for an unfavorable outcome after microvascular free flap reconstruction in head and neck cancer are not fully understood. We sought to identify factors affecting the occurrence of free flap failure. MATERIALS AND METHODS: This was a retrospective cohort study using data from the national inpatient database in Japan between 2010 and 2012. We identified patients diagnosed with head and neck cancer who underwent tumor resection and consecutive free flap reconstruction. Cox proportional hazards regression was used to assess risk factors for free flap failure. The threshold for significance was P < .05. Missing data were imputed by using multiple imputation. RESULTS: We identified 2,846 eligible patients. The overall proportion of free flap failure was 3.3%. Free flap failure was associated with diabetes mellitus (hazard ratio [HR], 1.80; 95% confidence interval [95% CI], 1.18 to 2.76; P = .007), peripheral vascular disease (HR, 4.49; 95% CI, 1.61 to 12.52; P = .004), renal failure (HR, 3.67; 95% CI, 1.45 to 9.33; P = .006), preoperative radiotherapy (HR, 2.14; 95% CI, 1.11 to 4.13; P = .022), and duration of anesthesia greater than 18 hours (compared with <12 hours; HR, 2.72; 95% CI, 1.19 to 6.22; P = .018). CONCLUSIONS: Diabetes mellitus, peripheral vascular disease, renal failure, preoperative radiotherapy, and a longer duration of anesthesia were significant predictors of the occurrence of free flap failure. PMID- 26851311 TI - Can Superselective Intra-Arterial Chemoradiotherapy Replace Surgery Followed by Radiation for Advanced Cancer of the Tongue and Floor of the Mouth? AB - PURPOSE: The purpose of this study was to compare quality of life (QoL) and the survival rate after surgery with and without radiotherapy versus superselective intra-arterial chemoradiotherapy (SSIACRT) for advanced cancer of the tongue and floor of the mouth. MATERIALS AND METHODS: Patients with stage III and IV squamous cell carcinoma of the tongue and floor of the mouth treated between 2000 and 2013 were included in this study. The predictor variables were surgery without radiotherapy, surgery followed by radiotherapy, and SSIACRT. The outcome variables were QoL and the survival rate. The University of Washington QoL questionnaire (UW-QOL) was used for evaluation of QoL. The Kaplan-Meier method was used to estimate the overall survival rate. The UW-QOL was analyzed by analysis of covariance, and the survival rate was analyzed statistically by the log-rank test. RESULTS: Sixty-two patients were eligible for this study. Of these, 13 were treated by surgery without radiotherapy, 29 were treated by surgery plus radiotherapy, and 20 were treated by SSIACRT. The SSIACRT group had the best UW-QOL scores among the 3 groups. The 5-year Kaplan-Meier disease specific survival rates for these groups were 92.9%, 62.9%, and 83.2%, respectively, with no significant difference (P = .20) shown. CONCLUSIONS: The QoL scores of the SSIACRT group were the best among the 3 groups in most domains. The superiority of QoL and the survival rate in the SSIACRT group showed that SSIACRT should be preferred in managing advanced cancer of the tongue and floor of the mouth. PMID- 26851312 TI - Health Insurance Affects Head and Neck Cancer Treatment Patterns and Outcomes. AB - PURPOSE: The purpose of this study is to examine the effect of insurance coverage on stage of presentation, treatment, and survival of head and neck cancer (HNC). MATERIALS AND METHODS: A retrospective study was conducted using the Surveillance, Epidemiology, and End Results (SEER) program to identify patients diagnosed with HNC. The primary variable of interest was insurance analyzed as a dichotomous variable: Patients were considered uninsured if they were classified as "uninsured" by SEER, whereas patients were considered insured if they were defined by SEER as "any Medicaid," "insured," or "insured/no specifics." The outcomes of interest were cancer stage at presentation (M0 vs M1), receipt of definitive treatment, and HNC-specific mortality (HNCSM). Multivariable logistic regression modeled the association between insurance status and stage at presentation, as well as between insurance status and receipt of definitive treatment, whereas HNCSM was modeled using Fine and Gray competing risks. Sensitivity logistic regression analysis was used to determine whether observed interactions remained significant by insurance type (privately insured, Medicaid, and uninsured). RESULTS: Patients without medical insurance were more likely to present with metastatic cancer (adjusted odds ratio, 1.60; P < .001), were more likely to not receive definitive treatment (adjusted odds ratio, 1.64; P < .001), and had a higher risk of HNCSM (adjusted hazard ratio, 1.20; P = .002). Sensitivity analyses showed that when results were stratified by insurance type, significant interactions remained for uninsured patients and patients with Medicaid. CONCLUSIONS: Uninsured patients and patients with Medicaid are more likely to present with metastatic disease, are more likely to not be treated definitively, and are at a higher risk of HNCSM. The treatment gap between Medicaid and private insurance observed in this study should serve as an immediate policy target for health care reform. PMID- 26851313 TI - Why Do Women Choose to Enter Academic Oral and Maxillofacial Surgery? AB - PURPOSE: To determine why women choose to enter an academic career in oral and maxillofacial surgery (OMS). MATERIALS AND METHODS: An online questionnaire was developed and e-mailed to female OMS surgeons to assess the reasons women choose to pursue an academic career, the perceived positive and negative features of academia for women, and proposed measures to increase the percentage of women choosing to specialize in OMS and pursue an academic career. RESULTS: Thirty-one female OMS surgeons completed the questionnaire; 1 additional participant accessed the survey but did not respond to any of the questions. There were 25 full-time academics and 6 part-time academics (>=50% time commitment). Of the responders, 72% were married, and of these, 72% were married before entering academics. Forty-seven percent of the women had children, all during their academic tenure. Among the full-time academicians with children, only 2 (7.7%) reported moderate difficulty finding the time for childbirth and maternity leave, whereas 3 of the 5 part-time academics with children reported moderate or significant difficulty with childbirth and maternity leave. Factors associated with choosing and enjoying an academic career are involvement in resident-student teaching (78%), followed by colleague camaraderie and collaboration (65.6%), research potential (50%), time flexibility, and not having to deal with excessive "business" practice issues (33%). The main reason for considering leaving an academic OMS career and/or among the least enjoyable aspects of being in academics was the potential for a higher income in private practice (56%). Less significant reasons for considering leaving an academic OMS career were a more flexible work schedule in the private sector and less institutional red tape (37.5%), as well as independence/being in control and more family time (22%). Engaging residents and students by female OMS surgeons, better mentorship from academic OMS surgeons, and increasing the number of women serving in leadership positions in organized OMS were identified as the most important measures to increase female involvement in academic OMS. CONCLUSIONS: This study shows that among the major motivating factors for choosing an academic career are involvement in resident-student teaching and colleague camaraderie and collaboration. Additional important factors for making this career choice are the research potential in academia, time flexibility, and not having to deal with excessive business practice issues. The reasons that deter women from entering OMS as a specialty and choosing a full-time academic OMS career are not significantly related to childbirth and family life. The main reason for potentially considering leaving an academic OMS career and/or among the least enjoyable aspects of being in academics is the potential for a higher income in private practice. Other reasons for potentially considering leaving an academic OMS career indicated by this study are independence/being in control and more family time, as well as the lack of institutional red tape. It appears that engaging female residents and students by female OMS surgeons, better mentorship by (both male and female) academic OMS surgeons, and increasing the number of female surgeons who can serve as role models may be beneficial in increasing the number of female OMS surgeons interested in an academic career. PMID- 26851314 TI - AMD3100 Attenuates Matrix Metalloprotease-3 and -9 Expressions and Prevents Cartilage Degradation in a Monosodium Iodo-Acetate-Induced Rat Model of Temporomandibular Osteoarthritis. AB - PURPOSE: Temporomandibular joint osteoarthritis (TMJOA) is an important subtype of temporomandibular disorder. This study investigated the inflammatory role of the stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor-4 (CXCR4) axis and the probable signaling pathway involved in matrix metalloprotease (MMP) 3 and MMP-9 productions stimulated by the SDF-1-CXCR4 axis in an experimental rat model of TMJOA. MATERIALS AND METHODS: Rats were randomly divided into a control group, a pathologic model group, and an AMD3100 group. Effects of the bicyclam derivative AMD3100 (the specific antagonist of SDF-1-CXCR4 axis) were studied in TMJOA experimentally induced by monosodium iodo-acetate. Productions of SDF-1 and CXCR4 were compared in the normal and pathologic model groups, and cartilage changes and expressions of MMP-3, MMP-9, and phosphorylated extracellular signal regulated kinase (p-ERK) were compared in the control, pathologic model, and AMD3100 groups. RESULTS: Expressions of SDF-1 and CXCR4 in the pathologic model group were increased compared with the control group (P < .05). Releases of MMP 3, MMP-9, and p-ERK and cartilage changes were downregulated in the AMD3100 group compared with the pathologic model group (P < .05), and these changes occurred in a dose-dependent manner with AMD3100 concentrations. Moreover, there were strong predictive relations between the expression of p-ERK with MMP-3 (r(2) = 0.419; P < .001) and with MMP-9 (r(2) = 0.542; P < .001). CONCLUSIONS: The SDF-1-CXCR4 signaling pathway plays a proinflammatory role in experimental TMJOA, the bicyclam derivative AMD3100 can alleviate the severity of experimental TMJOA, and there might be a potential relation between the SDF-1-CXCR4 axis and the ERK signaling pathway. PMID- 26851315 TI - In Reply. PMID- 26851316 TI - Virtual Surgical Planning in Precise Maxillary Reconstruction With Vascularized Fibular Graft After Tumor Ablation. AB - PURPOSE: Reconstruction of maxillary and midfacial defects due to tumor ablation is challenging to conventional operation. The purposes of this study are to evaluate the precise 3-dimensional position of the fibular flap in reconstruction of maxillary defects assisted by virtual surgical planning and to assess the postoperative outcomes compared with conventional surgery. MATERIALS AND METHODS: We retrospectively reviewed 18 consecutive patients who underwent maxillary reconstruction with a vascularized fibular flap assisted by virtual surgical planning after maxillary or midfacial tumor ablation. Conventional surgery was performed in another 15 patients. Proplan CMF surgical planning (Materialise, Leuven, Belgium) was performed preoperatively in the virtual planning group. Fibular flaps were harvested and underwent osteotomy assisted by prefabricated cutting guides, and the maxilla and midface were resected and reconstructed assisted by the prefabricated cutting guides and templates in the virtual planning group. The operative time and fibular flap positions were evaluated in the 2 groups. Postoperative fibular positions of the maxillary reconstruction were compared with virtual plans in the virtual planning group. The postoperative facial appearance and occlusal function were assessed. RESULTS: The operations were performed successfully without complications. The ischemia time and total operative time were shorter in the virtual planning group than those in the conventional surgery group (P < .05). High precision of the cutting guides and templates was found on both the fibula and maxilla in the virtual planning group. The positions of the fibular flaps, including the vertical and horizontal positions, were more accurate in the virtual planning group than those in the conventional surgery group (P < .05). Bone-to-bone contact between the maxilla and fibular segments was more precise in the virtual planning group (P < .05). Postoperative computed tomography scans showed excellent contour of the fibular flap segments in accordance with the virtual plans in the virtual planning group. All patients were alive with no evidence of disease. Functional mandibular range of motion, good occlusion, and an ideal facial appearance were observed in the virtual planning group. CONCLUSIONS: Virtual surgical planning appears to achieve precise maxillary reconstruction with a vascularized fibular flap after tumor ablation, as well as an ideal facial appearance and function after dental rehabilitation. The use of prefabricated cutting guides and plates eases fibular flap molding and placement, minimizes operating time, and improves clinical outcomes. PMID- 26851317 TI - Impact of Body Mass Index on the Outcomes of Open Reduction for Mandibular Fractures. AB - PURPOSE: Little is known about the impact of body mass index (BMI) on the postoperative outcomes of open reduction for mandibular fractures. The aim of this study was to investigate the relationship between BMI and short-term outcomes of surgery for mandibular fractures. MATERIALS AND METHODS: We searched the Japanese Diagnosis Procedure Combination database to identify patients who underwent open reduction for mandibular fractures from July 2010 to March 2013. BMI was divided into three groups: less than 18.5 kg/m(2) (underweight), 18.5 to 24.9 kg/m(2) (normal weight), and 25 kg/m(2) or greater (overweight). The outcomes included postoperative complication rates, duration of anesthesia, length of stay, and total costs. We analyzed the relationships between BMI and the outcomes by multivariable regression analyses. RESULTS: We analyzed 309 patients who underwent open reduction for mandibular fractures during the study period. The group with a BMI of 25 kg/m(2) or greater had a significantly longer hospital stay (3.8 days; 95% confidence interval, 0.5 to 7.1 days, P = .03) than the group with a normal BMI. BMI was not significantly associated with duration of anesthesia, postoperative complication rates, or total costs. CONCLUSIONS: Regarding open reduction for mandibular fractures, overweight status may be associated with a prolonged length of stay, but may have little impact on operating time, postoperative morbidity, or overall costs. PMID- 26851318 TI - Longitudinal Contraction Venoplasty in Prevention of Internal Jugular Vein Thrombosis After Free Flap Vascular Anastomosis. AB - PURPOSE: The vascular anastomosis of free flap with the internal jugular vein stump is susceptible to thrombosis, thus resulting in flap compromise or failure. This study aims to explore the method of longitudinal contraction venoplasty in the prevention of internal jugular vein stump thrombosis after free flap vascular anastomosis and its feasibility. PATIENTS AND METHODS: A retrospective review was performed of 16 patients who underwent internal jugular vein resection because of cancer ablation and longitudinal contraction venoplasty to prevent internal jugular vein stump thrombosis after free flap vascular anastomosis from January 2013 through December 2014 at Second Xiangya Hospital. The methods for longitudinal contraction venoplasty and its efficacy are reported. RESULTS: Venous anastomosis of all flaps was performed with the internal jugular vein stump, and single venous anastomosis was made in all cases. Postoperatively, all flaps survived completely, without vascular compromise. All the patients were followed for approximately 9 to 33 months, and they were satisfied with the esthetic and functional results of the donor and recipient sites after reconstruction. CONCLUSIONS: Longitudinal contraction venoplasty may be an effective new method for prevention of internal jugular vein thrombosis after free flap vascular anastomosis. PMID- 26851319 TI - Idiopathic First Bite Syndrome. PMID- 26851320 TI - Primary process: why psychiatry and general practice should collaborate. PMID- 26851321 TI - Neuropathology: bridging psychiatry and neurology in medical education. PMID- 26851322 TI - The digital placebo effect: mobile mental health meets clinical psychiatry. PMID- 26851323 TI - Risk of bias in observational studies of interventions: the case of antipsychotic induced diabetes. PMID- 26851324 TI - Risk of bias in observational studies of interventions: the case of antipsychotic induced diabetes - Authors' reply. PMID- 26851325 TI - Long-term lithium and estimated glomerular filtration rate. PMID- 26851326 TI - Doubtful comparison group. PMID- 26851327 TI - Long-term lithium and estimated glomerular filtration rate - Authors' reply. PMID- 26851329 TI - Effectiveness of traditional healers in treating mental disorders: a systematic review. AB - Traditional healers form a major part of the mental health workforce worldwide. Despite this, little systematic examination has been done of their effectiveness in treating mental illness or alleviating psychological distress. In this Review, we aim to fill this gap, with a focus on quantitative outcomes. We searched four databases and reference lists for papers that explicitly measured the effectiveness of traditional healers on mental illness and psychological distress. Eligible papers were assessed for quality, and outcomes and other details were extracted with the use of a standardised template. 32 eligible papers from 20 countries were included. The published literature on this topic is heterogeneous and studies are generally of poor quality, although some findings emerge more consistently. Some evidence suggests that traditional healers can provide an effective psychosocial intervention. Their interventions might help to relieve distress and improve mild symptoms in common mental disorders such as depression and anxiety. However, little evidence exists to suggest that they change the course of severe mental illnesses such as bipolar and psychotic disorders. Nevertheless, qualitative changes that are captured poorly by conventional rating scales might be as important as the quantitative changes reviewed here. We conclude by outlining the challenges involved in assessing the effectiveness of traditional healers. PMID- 26851330 TI - Estimating the true global burden of mental illness. AB - We argue that the global burden of mental illness is underestimated and examine the reasons for under-estimation to identify five main causes: overlap between psychiatric and neurological disorders; the grouping of suicide and self-harm as a separate category; conflation of all chronic pain syndromes with musculoskeletal disorders; exclusion of personality disorders from disease burden calculations; and inadequate consideration of the contribution of severe mental illness to mortality from associated causes. Using published data, we estimate the disease burden for mental illness to show that the global burden of mental illness accounts for 32.4% of years lived with disability (YLDs) and 13.0% of disability-adjusted life-years (DALYs), instead of the earlier estimates suggesting 21.2% of YLDs and 7.1% of DALYs. Currently used approaches underestimate the burden of mental illness by more than a third. Our estimates place mental illness a distant first in global burden of disease in terms of YLDs, and level with cardiovascular and circulatory diseases in terms of DALYs. The unacceptable apathy of governments and funders of global health must be overcome to mitigate the human, social, and economic costs of mental illness. PMID- 26851331 TI - Anorexia nervosa and body-image disturbance - Authors' reply. PMID- 26851332 TI - Measuring substance misuse in trafficked people. PMID- 26851333 TI - Anorexia nervosa and body-image disturbance. PMID- 26851334 TI - New "Profiles" for tomorrow's health professionals: Welcome! We need you. PMID- 26851335 TI - Concurrent Validity of a Self-Reported Physical Activity "Vital Sign" Questionnaire With Adult Primary Care Patients. AB - INTRODUCTION: No tool currently used by primary health care providers to assess physical activity has been evaluated for its ability to determine whether or not patients achieve recommended levels of activity. The purpose of this study was to assess concurrent validity of physical activity self-reported to the brief (<30 sec) Physical Activity "Vital Sign" questionnaire (PAVS) compared with responses to the lengthier (3-5 min), validated Modifiable Activity Questionnaire (MAQ). METHODS: Agreement between activity reported to the PAVS and MAQ by primary care patients at 2 clinics in 2014 was assessed by using percentages and kappa coefficients. Agreement consisted of meeting or not meeting the 2008 Aerobic Physical Activity Guidelines for Americans (PA Guidelines) of the US Department of Health and Human Services. We compared self-reported usual minutes per week of moderate-to-vigorous physical activity among patients at a primary care clinic in 2014 who reported to PAVS and to MAQ by using Pearson correlation and Bland Altman plots of agreement. RESULTS: Among 269 consenting patients who reported physical activity, PAVS results agreed with those of MAQ 89.6% of the time and demonstrated good agreement in identifying patients who did not meet PA Guidelines recommendations (kappa = 0.55, rho = 0.57; P < .001). Usual minutes per week of moderate-to-vigorous physical activity reported to PAVS had a high positive correlation with the same reported to MAQ (r = 0.71; P < .001). CONCLUSION: PAVS may be a valid tool for identifying primary care patients who need counseling about physical activity. PAVS should be assessed further for agreement with repeated objective measures of physical activity in the patient population. PMID- 26851336 TI - How Tobacco Quitline Callers in 38 US States Reported Hearing About Quitline Services, 2010-2013. AB - INTRODUCTION: Telephone-based tobacco quitlines are an evidence-based intervention, but little is known about how callers hear about quitlines and whether variations exist by demographics or state. This study assessed trends in "how-heard-abouts" (HHAs) in 38 states. METHODS: Data came from the Centers for Disease Control and Prevention's (CDC's) National Quitline Data Warehouse, which stores nonidentifiable data collected from individual callers at quitline registration and reported quarterly by states. Callers were asked how they heard about the quitline; responses were grouped into the following categories: media, health professional, family or friends, and "other." We examined trends from 2010 through 2013 (N = 1,564,437) using multivariable models that controlled for seasonality and the impact of CDC's national tobacco education campaign, Tips From Former Smokers (Tips). Using data from 2013 only, we assessed HHAs variation by demographics (sex, age, race/ethnicity, education) and state in a 38-state sample (n = 378,935 callers). RESULTS: From 2010 through 2013, the proportion of HHAs through media increased; however, this increase was not significant when we controlled for calendar quarters in which Tips aired. The proportion of HHAs through health professionals increased, whereas those through family or friends decreased. In 2013, HHAs occurred as follows: media, 45.1%; health professionals, 27.5%, family or friends, 17.0%, and other, 10.4%. Media was the predominant HHA among quitline callers of all demographic groups, followed by health professionals (except among people aged 18-24 years). Large variations in source of HHAs were observed by state. CONCLUSION: Most quitline callers in the 38-state sample heard about quitlines through the media or health care professionals. Variations in source of HHAs exist across states; implementation of best-practice quitline promotional strategies is critical to maximize reach. PMID- 26851337 TI - Assessment of a University Campus Food Environment, California, 2015. AB - INTRODUCTION: University campuses offer an opportunity to study the extent to which modifying the food environment influences eating, but in-depth characterizations of campus food environments are needed to identify potential targets for intervention. The objective of this project was to describe the availability, accessibility, and quality of healthful food choices in dining venues and food stores at or near a public, 4-year university in California. METHODS: Trained assessors used the Nutrition Environment Measures Survey for campus dining (NEMS-CD) to evaluate all 18 campus dining venues, and NEMS for stores (NEMS-S) to evaluate 2 on-campus and 37 off-campus food stores. We calculated prevalence of healthful and unhealthful constructs (eg, availability of selected food items, presence of signage encouraging healthful eating, pricing options that encourage healthful eating), based on the NEMS and compared scores across different types of venues. RESULTS: NEMS-CD scores ranged from 4 to 47 (mean [SD], 26.0 [14.4]) out of a possible maximum score of 97; 12% of entrees and 36% of main dish salads served in these venues were classified as healthful. NEMS-S score for the 2 on-campus food stores (24 for both) was intermediate between off-campus convenience stores (mean [SD], 12.0 [5.3]) and grocery/supermarket stores (mean [SD], 31.1 [10.0]), with a possible maximum score of 54. CONCLUSION: Standardized environmental evaluation provides insights into both positive and negative aspects of campus community food venues. Environmental assessment identifies potential targets for modification and baseline data for designing and implementing action-oriented research aimed at improving the campus food environment's support of healthful food choices for college students. PMID- 26851338 TI - Diabetes Status and Being Up-to-Date on Colorectal Cancer Screening, 2012 Behavioral Risk Factor Surveillance System. AB - INTRODUCTION: Although screening rates for colorectal cancer are increasing, 22 million Americans are not up-to-date with recommendations. People with diabetes are an important and rapidly growing group at increased risk for colorectal cancer. Screening status and predictors of being up-to-date on screening are largely unknown in this population. METHODS: This study used logistic regression modeling and data from the 2012 Behavioral Risk Factor Surveillance System to examine the association between diabetes and colorectal cancer screening predictors with being up-to-date on colorectal cancer screening according to criteria of the US Preventive Services Task Force for adults aged 50 or older. State prevalence rates of up-to-date colorectal cancer screening were also calculated and mapped. RESULTS: The prevalence of being up-to-date with colorectal cancer screening for all respondents aged 50 or older was 65.6%; for respondents with diabetes, the rate was 69.2%. Respondents with diabetes were 22% more likely to be up-to-date on colorectal cancer screening than those without diabetes. Among those with diabetes, having a routine checkup within the previous year significantly increased the odds of being up-to-date on colorectal cancer screening (odds ratio, 1.90). Other factors such as age, income, education, race/ethnicity, insurance status, and history of cancer were also associated with up-to-date status. CONCLUSION: Regardless of diabetes status, people who had a routine checkup within the past year were more likely to be up-to-date than people who had not. Among people with diabetes, the duration between routine checkups may be of greater importance than the frequency of diabetes-related doctor visits. Continued efforts should be made to ensure that routine care visits occur regularly to address the preventive health needs of patients with and patients without diabetes. PMID- 26851339 TI - An effective thiol-reactive probe for differential scanning fluorimetry with a standard real-time polymerase chain reaction device. AB - Differential scanning fluorimetry (DSF) is used to assess protein stability, transition states, or the Kd values of various ligands, drug molecules, and antibodies. All fluorescent probes published to date either are incompatible with hydrophobic proteins/ligands, precluding analyses of transmembrane or membrane associated proteins, or have excitation and detection wavelengths outside the range of real-time polymerase chain reaction (RT-PCR) machines, necessitating the use of dedicated devices. Here, we describe a thiol-reactive probe, BODIPY FL L cystine (BFC), to overcome both of these shortcomings. The probe supports an inexpensive application of DSF measurements suitable for detection with standard RT-PCR machines in a hydrophilic or hydrophobic environment. PMID- 26851340 TI - DRME: Count-based differential RNA methylation analysis at small sample size scenario. AB - Differential methylation, which concerns difference in the degree of epigenetic regulation via methylation between two conditions, has been formulated as a beta or beta-binomial distribution to address the within-group biological variability in sequencing data. However, a beta or beta-binomial model is usually difficult to infer at small sample size scenario with discrete reads count in sequencing data. On the other hand, as an emerging research field, RNA methylation has drawn more and more attention recently, and the differential analysis of RNA methylation is significantly different from that of DNA methylation due to the impact of transcriptional regulation. We developed DRME to better address the differential RNA methylation problem. The proposed model can effectively describe within-group biological variability at small sample size scenario and handles the impact of transcriptional regulation on RNA methylation. We tested the newly developed DRME algorithm on simulated and 4 MeRIP-Seq case-control studies and compared it with Fisher's exact test. It is in principle widely applicable to several other RNA-related data types as well, including RNA Bisulfite sequencing and PAR-CLIP. The code together with an MeRIP-Seq dataset is available online (https://github.com/lzcyzm/DRME) for evaluation and reproduction of the figures shown in this article. PMID- 26851341 TI - A strategy to quantitate global phosphorylation of bone matrix proteins. AB - Current studies of protein phosphorylation focus primarily on the importance of specific phosphoproteins and their landscapes of phosphorylation in the regulation of different cellular functions. However, global changes in phosphorylation of extracellular matrix phosphoproteins measured "in bulk" are equally important. For example, correct global phosphorylation of different bone matrix proteins is critical to healthy tissue biomineralization. To study changes of bone matrix global phosphorylation, we developed a strategy that combines a procedure for in vitro phosphorylation/dephosphorylation of fully mineralized bone in addition to quantitation of the global phosphorylation levels of bone matrix proteins. For the first time, we show that it is possible to enzymatically phosphorylate/dephosphorylate fully mineralized bone originating from either cadaveric human donors or laboratory animals (mice). Using our strategy, we detected the difference in the global phosphorylation levels of matrix proteins isolated from wild-type and osteopontin knockout mice. We also observed that the global phosphorylation levels of matrix proteins isolated from human cortical bone were lower than those isolated from trabecular bone. The developed strategy has the potential to open new avenues for studies on the global phosphorylation of bone matrix proteins and their role in biomineralization as well for other tissues/cells and protein-based materials. PMID- 26851342 TI - Interocular grouping without awareness. AB - Interocular grouping occurs when different parts of an image presented to each eye bound into a coherent whole. Previous studies anticipated that these parts are visible to both eyes simultaneously (i.e., the images altered back and forth). Although this view is consistent with the general consensus of binocular rivalry (BR) that suppressed stimuli receive no processing beyond rudimentary level (i.e., adaptation), it is actually inconsistent with studies that use continuous flash suppression (CFS). CFS is a form of interocular suppression that is more stable and causes stronger suppression of stimuli than BR. In the present study, we examined whether or not interocular grouping needs to occur at a conscious level as prior studies suggested. The modified double-rectangle paradigm used by Egly, Driver, and Rafal (1994) was adopted, and object-based attention was directed for successful grouping. To induce interocular grouping, we presented complementary parts of two rectangles dichoptically for possible interocular grouping and a dynamic Mondrian in front of one eye (i.e., CFS). Two concurrent targets were presented after one of the visible parts of the rectangles was cued. Participants were asked to judge which target appeared first. We found that the target showed on the cued rectangle after interocular grouping was reported to appear first more frequently than the target on the uncued rectangle. This result was based on the majority of trials where the suppressed parts of the objects remained invisible, which indicates that interocular grouping can occur without all the to-be-grouped parts being visible and without awareness. PMID- 26851343 TI - Understanding the statistics of the natural environment and their implications for vision. PMID- 26851344 TI - Quassinoids from the stems of Picrasma quassioides and their cytotoxic and NO production-inhibitory activities. AB - Three new C20 quassinoids nigakilactone P (1), picraqualide F (2), nigakilactone Q (3), along with eight known quassinoids (4-11), were isolated from the 95% EtOH extract of the stems of Picrasma quassioides. The structures of the new compounds were elucidated by means of HRESIMS and different NMR techniques. Assignments of relative and absolute configurations for these compounds were achieved on the basis of ROESY spectra and quantum chemical ECD calculation. In vitro activity assays, none of the compounds showed cytotoxic (IC50>50 MUM) and NO production inhibitory activities (IC50>30 MUM), and the structure-activity relationships of quassinoids were summarized. In addition, the chemotaxonomic significance of the isolated compounds was also discussed. PMID- 26851345 TI - Heat Shock Protein 72 Antagonizes STAT3 Signaling to Inhibit Fibroblast Accumulation in Renal Fibrogenesis. AB - Heat shock protein 72 (HSP72) has been shown to attenuate unilateral ureteral obstruction-induced kidney fibrosis. It remains unknown whether HSP72 has direct effects on fibroblast proliferation in the renal fibrotic evolution. Herein, we first confirmed that increased HSP72 expression occurred in fibrotic human kidneys. Using three different animal models of kidney fibrosis, pharmacological down-regulation or genetic deletion of endogenous HSP72 expression exacerbated STAT3 phosphorylation, fibroblast proliferation, and tubulointerstitial fibrosis. In contrast, treatment with geranylgeranyl acetone, a specific inducer of HSP72, reduced phosphorylated STAT3 and protected animals from kidney fibrosis. In cultured renal interstitial fibroblasts, overexpression of HSP72 blocked transforming growth factor (TGF)-beta1-induced cell activation and proliferation, as evidenced by inhibiting expression of alpha-smooth muscle actin, fibronectin, and collagen I/III, as well as by reducing cell numbers and DNA synthesis. Mechanical studies showed that overexpressed HSP72 attenuated TGF-beta-induced phosphorylation and nuclear translocation of STAT3 and its downstream protein expression. However, siRNA knockdown of HSP72 increased TGF-beta-induced STAT3 activity and fibroblast proliferation. Ectopic expression of a constitutively active STAT3 conferred resistance to HSP72 inhibition of fibroblast proliferation. Thus, HSP72 blocks fibroblast activation and proliferation in renal fibrosis via targeting the STAT3 pathway and may serve as a novel therapeutic agent for chronic kidney disease regardless of the etiology. PMID- 26851346 TI - 1,25-Vitamin D3 Deficiency Induces Albuminuria. AB - Vitamin D plays an important role in renal (patho)physiology. Patients with glomerular diseases have an injured renal filtration barrier, leading to proteinuria and reduced renal function. An impaired renal function also leads to 1,25-vitamin D3 deficiency as a result of reduced renal 1alpha-hydroxylase activity. Vitamin D treatment to reduce proteinuria remains controversial, although there is an inverse correlation between vitamin D levels and proteinuria. Herein, we showed that 1,25-vitamin D3-deficient 25-hydroxy-vitamin D3-1alpha-hydroxylase knockout mice and 1,25-vitamin D3-deficient rats develop podocyte injury and renal dysfunction. Glomerular injury was characterized by proteinuria and partial podocyte foot process effacement. Expression of nephrin, podocin, desmin, and transient receptor potential channel C6 in the podocyte was significantly altered in 1,25-vitamin D3-deficient animals. Supplementation with 1,25-vitamin D3 or 1,25-vitamin D2 prevented podocyte effacement or reversed glomerular and tubulointerstitial damage in 1,25-vitamin D3-deficient animals, thereby preserving and restoring renal function, respectively. The effect of 1,25 vitamin D3 deficiency and 1,25-vitamin D3 and 1,25-vitamin D2 repletion on proteinuria could not be explained by hypocalcemia, changes in parathyroid hormone, or fibroblast growth factor 23. This study demonstrates that 1,25 vitamin D3 deficiency directly leads to renal injury in rodents. Translated to human subjects, this would underline the need for early vitamin D supplementation in patients with glomerular disease and chronic renal insufficiency, which might inhibit or potentially reverse renal injury. PMID- 26851347 TI - Characterizing Villitis of Unknown Etiology and Inflammation in Stillbirth. AB - Villitis of unknown etiology (VUE) is an enigmatic inflammatory condition of the placenta associated with fetal growth restriction and stillbirth. Greater understanding of this condition is essential to understand its contribution to adverse outcomes. Our aim was to identify and quantify the cells in VUE in cases of stillbirth and to characterize immune responses specific to this condition. Immunohistochemistry was performed on placentas from stillborn infants whose cause of death was recorded as VUE to identify CD45(+) leukocytes, CD163(+) macrophages, CD4(+) and CD8(+) T cells, neutrophils, and proinflammatory and anti inflammatory cytokines. Images were quantified with HistoQuest software. CD45(+) leukocytes comprised 25% of cells in VUE lesions: macrophages (12%) and CD4 T cells (11%) being predominant cell types; CD8 T cells were observed in all lesions. Leukocytes and macrophages were increased throughout the placenta in stillbirths; pan-placental CD4(+) and CD8(+) T cells outside VUE lesions were increased in stillbirth with VUE. There was increased IL-2 and IL-12 and reduced IL-4 immunostaining in VUE lesions. Our results suggest VUE in stillbirth has a similar immune cell profile to live birth. Pan-placental macrophages, CD4 and CD8 T cells indicate a wider inflammatory response unrestricted to VUE lesions. The cytokine profile observed suggests a skew towards inappropriate Th1 immune responses. Full characterisation VUE lesion phenotype confirms its immunological origins and provides foundations to develop novel investigations. PMID- 26851348 TI - Immune mechanisms of acute and chronic rejection. AB - With the currently available immunosuppression, severe T-cell mediated rejection has become a rare event. With the introduction of modern antibody-detection techniques, such as the L-SAB technology, acute or hyperacute antibody-mediated rejection of the kidney are also seen infrequently. In contrast, chronic antibody mediated rejection is considered to be a major contributor to graft loss in the late posttransplant phase. Problems in the management of chronic antibody mediated rejection are effective prevention of the development of alloantibodies against donor HLA and the early identification of patients at risk for this entity. Finally, today there is still noeffective strategy to treat this indolent and slowly progressing form of antibody-mediated rejection. Herein, we review the pathomechanisms of the different forms of rejection and the clinical significance of these entities in human kidney transplantation. PMID- 26851349 TI - Hair ethyl glucuronide and serum carbohydrate deficient transferrin for the assessment of relapse in alcohol-dependent patients. AB - OBJECTIVES: Ethyl glucuronide in hair (hEtG) and serum carbohydrate deficient transferrin (%CDT) are valuable markers for alcohol abuse, but their diagnostic accuracy to monitor abstinence and relapse is unclear. Here, we investigate to what extent repeated measurements of hEtG and %CDT can be used to monitor relapse in alcohol-dependent patients during abstinence treatment. DESIGN AND METHODS: HEtG and %CDT were measured in individuals starting treatment for alcohol dependence both at treatment entry and 3months later. Alcohol consumption and relapse episodes were recorded using the Time Line Follow Back and by alcohol breath and urine tests, and correlated with hEtG and %CDT measurements. RESULTS: Fifteen patients completed the study, of which nine had one or more relapses. Hair EtG and serum %CDT identified whether a relapse occurred in 78% and 57% of cases, respectively. Only hEtG correlated with the amount of alcohol consumed before treatment entry (Pearson r=0.92; p<0.001). The specificity of %CDT to assess abstinence during treatment was 100%. HEtG had a specificity of only 17%; however, in all patients who remained abstinent, hEtG decreased with >85% from initial values. Mean hEtG, but not %CDT, differed significantly between patients who relapsed and patients who remained abstinent (p=0.034). CONCLUSIONS: HEtG was more sensitive than serum %CDT to assess relapse in alcohol-dependent patients and was positively correlated with the amounts of alcohol consumed. In contrast, serum %CDT was more specific for assessing abstinence. We highlight the benefit of repeated measurements of hEtG and serum %CDT for monitoring abstinence during treatment. PMID- 26851350 TI - The Italian pilot external quality assessment program for cystic fibrosis sweat test. AB - OBJECTIVES: Sweat chloride test is the gold standard test for cystic fibrosis (CF) diagnosis. In 2014 the Istituto Superiore di Sanita established the Italian pilot external quality assessment program for CF sweat test (IEQA-ST). DESIGN AND METHODS: Ten laboratories, included among the 33 Italian CF Referral Centers, were selected and enrolled on the basis of their attitude to perform sweat test (ST) analysis by using methods recommended by the Italian Guidelines. They received three different sweat-like samples (normal, borderline and pathologic chloride concentration), with mock clinical indications, for analysis according to routine procedures. Assessment, performed by a panel of experts, covered analytical performance, interpretation and reporting of results; categories of "poor" and "satisfactory" performance were not defined. All data were managed through a web utility. RESULTS: The program identified important areas of interest and, in some case, of concern. It is important to underline that results are referred to a small proportion, i.e. about 30%, of Italian laboratories performing CF ST in the context of the Referral Centers. CONCLUSIONS: Data collected highlight the importance of participation in EQA programs as it may improve laboratory/clinical performance; our study represents a model for the setting up of a large-scale EQA scheme for ST. PMID- 26851351 TI - A retrospective analysis of meningioma in Central Texas. AB - Documented meningioma cases in Central Texas (USA) from 1976 to 2013 were studied utilizing the Scott & White Brain Tumor Registry. All the cases examined were histologically diagnosed as meningiomas. Of the 372 cases, most were benign tumors (p<0.05). A majority of the patients were females (p<0.05). Elderly individuals (>45years of age) superseded the younger patients in meningioma incidence (p<0.05). Previous data regarding meningioma epidemiology in Texas showed a higher incidence in black patients when compared to white patients. By contrast, this study's findings of Central Texas meningioma demographics show increased incidence of meningiomas in white patients (p<0.05). This interesting find in meningioma prevalence warrants further investigation with a larger sample size, in order to establish validity and further parse out possible causes of meningioma development among white individuals. PMID- 26851352 TI - Accurate prediction of helix interactions and residue contacts in membrane proteins. AB - Accurate prediction of intra-molecular interactions from amino acid sequence is an important pre-requisite for obtaining high-quality protein models. Over the recent years, remarkable progress in this area has been achieved through the application of novel co-variation algorithms, which eliminate transitive evolutionary connections between residues. In this work we present a new contact prediction method for alpha-helical transmembrane proteins, MemConP, in which evolutionary couplings are combined with a machine learning approach. MemConP achieves a substantially improved accuracy (precision: 56.0%, recall: 17.5%, MCC: 0.288) compared to the use of either machine learning or co-evolution methods alone. The method also achieves 91.4% precision, 42.1% recall and a MCC of 0.490 in predicting helix-helix interactions based on predicted contacts. The approach was trained and rigorously benchmarked by cross-validation and independent testing on up-to-date non-redundant datasets of 90 and 30 experimental three dimensional structures, respectively. MemConP is a standalone tool that can be downloaded together with the associated training data from http://webclu.bio.wzw.tum.de/MemConP. PMID- 26851354 TI - Influence of hydrophilic polymers on functional properties and wound healing efficacy of hydrocolloid based wound dressings. AB - The purpose of this study was to investigate the influence of different hydrophilic polymers on the swelling, bioadhesion and mechanical strength of hydrocolloid wound dressings (HCDs) in order to provide an appropriate composition for a hydrocolloid wound dressing system. In this study, the HCDs were prepared with styrene-isoprene-styrene copolymer (SIS) and polyisobutylene (PIB) as the base using a hot melting method. Additionally, numerous SIS/PIB based HCDs were prepared with six hydrophilic polymers, and their wound dressing properties were assessed. Finally, the wound healing efficacy of the selected formulations was compared to a commercial wound dressing. The swelling ratio, bioadhesive force and mechanical strengths of HCDs were increased in the order of sodium alginate>sodium CMC=poloxamer=HPMC>PVA=PVP, sodium alginate>sodium CMC=poloxamer>PVA>HPMC=PVP and sodium alginate>=PVA>PVP=HPMC=sodium CMC>poloxamer, respectively. Among the hydrophilic polymers tested, sodium alginate most enhanced the swelling capacity, bioadhesive force and mechanical strengths. Thus, the hydrophilic polymers played great role in the swelling, bioadhesion and mechanical strength of SIS/PIB-based HCDs. The HCD formulation composed of PIB, SIS, liquid paraffin and sodium alginate at the weight ratio of 20/25/12/43 gave better wound dressing properties and more excellent wound healing efficacy than the commercial wound dressing. Therefore, the novel HCD formulation could be a promising hydrocolloid system for wound dressings. PMID- 26851353 TI - Daidzein-loaded nanostructured lipid carriers-PLGA nanofibers for transdermal delivery. AB - Daidzein is one of the most effective candidates for treating cardiovascular and cerebrovascular disease. However, considering its poor oral absorption and limited bioavailability, daidzein-loaded nanostructured lipid carriers-PLGA nanofibers were designed to handle the drawbacks. Daidzein-NLCs were successfully prepared by an emulsification and low-temperature solidification method. The physicochemical characteristics of NLCs were evaluated afterwards. Based on the preparation of daidzein-loaded NLCs, Daidzein-NLCs-nanofibers were optimized by electrospinning and were observed under Scanning Electron Microscope to capture the appearance. The sustained release profile of daidzein from Daidzein-NLCs nanofibers in vivo was best fitted to the Kormeyer-Peppas equation. The in vitro skin permeable behavior showed the cumulative amount of daidzein from Daidzein NLCs-nanofibers reached 21.71 MUg cm(-2) at 60 h, which was 3.78 times higher than pure daidzein solution. It demonstrated that the Daidzein-NLCs-nanofibers could significantly enhance the transported amount of drug. Confocal Laser Scanning Microscopy resulting images revealed a more effective content accumulation of Daidzein-NLCs-nanofibers than Daidzein-NLCs in epidermis. In vivo study indicated that Daidzein-NLCs-nanofibers had better skin retention than Daidzein-NLCs in the long term. The skin irritation experiment showed a positive result with no obvious stimulus observed. These results suggested that Daidzein NLCs-nanofibers could be a potential candidate for transdermal delivery. PMID- 26851355 TI - Continuous manufacturing of delta mannitol by cospray drying with PVP. AB - Mannitol is a frequently used diluent in the production of tablets due to its non hygroscopic character and low drug interaction potential. Although the delta polymorph of mannitol has superior tabletability in comparison to alpha- and beta mannitol, the latter are most commonly used because large-scale production of delta-mannitol is difficult. Therefore, a continuous method for production of delta-mannitol was developed in the current study. Spray drying an aqueous solution of mannitol and PVP in a ratio of 4:1 resulted in formation of delta mannitol. The tabletability of a physical mixture of spray dried delta-mannitol with PVP (5%) and paracetamol (75%) was clearly superior to the tabletability of physical mixtures consisting of spray dried alpha- and beta-mannitol with PVP (5%) and paracetamol (75%) which confirmed the excellent tableting properties of the delta-polymorph. In addition, a coprocessing method was applied to coat paracetamol crystals with delta-mannitol and PVP. The tabletability of the resulting coprocessed particles consisting of 5% PVP, 20% delta-mannitol and 75% paracetamol reached a maximal tensile strength of 2.1 MPa at a main compression pressure of 260 MPa. Moreover the friability of tablets compressed at 184 MPa was only 0.5%. This was attributed to the excellent compression properties of delta mannitol and the coating of paracetamol crystals with delta-mannitol and PVP during coprocessing. PMID- 26851356 TI - Coordinated pH/redox dual-sensitive and hepatoma-targeted multifunctional polymeric micelle system for stimuli-triggered doxorubicin release: Synthesis, characterization and in vitro evaluation. AB - Multifunctional polymeric micelles self-assembled from a DOX-conjugated methoxypolyethylene glycols-b-poly (6-O-methacryloyl-D-galactopyranose)-disulfide bond-DOX (mPEG-b-PMAGP-SS-DOX) copolymer were prepared as an antitumor carrier for doxorubicin delivery, of which the chemical modification with disulfide bonds and hydrazone bonds allowed micelles to release doxorubicin (DOX) selectively at acidic pH and high redox conditions. The resulting micelles exhibited coordinated pH/redox dual-sensitive and hepatoma-targeted multifunction with sustaining stability in aqueous media. The multifunctional micelles showed spherical shapes with a mean diameter of 93 +/- 2.08 nm, a low polydispersity index (PDI) of 0.21, a low CMC value of 0.095 mg/mL, a high drug grafting degree of 56.9% and a drug content of 39.0%. Remarkably, in vitro drug release studies clearly exhibited a pH and redox dual-sensitive drug release profile with significantly accelerated drug release treated with pH 5.0 and 10mM GSH (88.4% in 72 h) without drug burst release. The tumor proliferation assays indicated that DOX-grafted micelles, along with low cytotoxicity and well biocompatibility to normal cells up to a concentration of 10 MUg/mL, inhibited the proliferation of HepG2 cells in a formulation-, time- and concentration-dependent manner in comparison with MCF-7 cells which was similar to free DOX. Anticancer activity releaved that the disulfide-modified micelles possessed much higher anti-hepatoma activity with a low IC50 value of 1.1 MUg/mL following a 72 h incubation. Furthermore, the intracellular uptake tested by CLSM and FCM demonstrated that multifunctional polymeric micelles could be more efficiently taken up by HepG2 cells compared with MCF-7 cells, agreed well with MTT assays, suggesting these well-defined micelles provide a potential drug delivery system for dual-responsive controlled drug release and enhanced anti-hepatoma therapy. PMID- 26851357 TI - Biophysical stability of hyFc fusion protein with regards to buffers and various excipients. AB - A novel non-cytolytic hybrid Fc (hyFc) with an intact Ig structure without any mutation in the hyFc region, was developed to construct a long-acting agonistic protein. The stability of interleukin-7 (IL-7) fused with the hyFc (GXN-04) was evaluated to develop early formulations. Various biophysical methods were utilized and three different buffer systems with various pH ranges were investigated including histidine-acetate, sodium citrate, and tris buffers. Various excipients were incorporated into the systems to obtain optimum protein stability. Two evident thermal transitions were observed with the unfolding of IL 7 and hyFc. The Tm and DeltaH increased with pH, suggesting increased conformational stability. Increased Z-average size with PDI and decreased zeta potential with pH increase, with the exception of tris buffer, showed aggregation issues. Moreover, tris buffer at higher pH showed aggregation peaks from DLS. Non ionic surfactants were effective against agitation by outcompeting protein molecules for hydrophobic surfaces. Sucrose and sorbitol accelerated protein aggregation during agitation, but exhibited a protective effect against oxidation, with preferential exclusion favoring the compact states of GXN-04. The stability of GXN-04 was varied by basal buffers and excipients, hence the buffers and excipients need to be evaluated carefully to achieve the maximum stability of proteins. PMID- 26851358 TI - Molecular investigations of flaxseed mucilage polysaccharides. AB - The molecular properties of flaxseed mucilage were determined using a multi-angle laser light scattering (MALLS) detector coupled on-line to size exclusion chromatography (SEC) and asymmetric flow field-flow fractionation (AF4). Water and salt solution were tested as mobile phases. The SEC-MALLS method gave partial information and enabled molecular characterization of disaggregated mucilage molecules. Regardless of the eluent used, the observed Mw ranged from about 1.6 * 10(6) to more than 10 * 10(6) g/mol for mucilage polysaccharides. The AF4-MALLS system enabled a complete analysis of mucilage carbohydrate aggregates in water, in which two populations were satisfactorily separated. The molecular weight distribution (MWD) of molecules ranged from 1.5 * 10(6) to more than 4 * 10(8) g/mol. Experiments showed that the conformational structure of mucilage molecules was strongly influenced by ionic strength. Mucilage carbohydrates exhibited a spherical and compact structure in NaCl solution while they displayed a random coil conformation in water. PMID- 26851359 TI - Dendrimers, mesoporous silicas and chitosan-based nanosorbents for the removal of heavy-metal ions: A review. AB - The application of nanomaterials as nanosorbents in solving environmental problems such as the removal of heavy metals from wastewater has received a lot of attention due to their unique physical and chemical properties. These properties make them more superior and useful in various fields than traditional adsorbents. The present mini-review focuses on the use of nanomaterials such as dendrimers, mesoporous silicas and chitosan nanosorbents in the treatment of wastewater contaminated with toxic heavy-metal ions. Recent advances in the fabrication of these nanoscale materials and processes for the removal of heavy metal ions from drinking water and wastewater are highlighted, and in some cases their advantages and limitations are given. These next-generation adsorbents have been found to perform very well in environmental remediation and control of heavy metal ions in wastewater. The main objective of this review is to provide up-to date information on the research and development in this particular field and to give an account of the applications, advantages and limitations of these particular nanosorbents in the treatment of aqueous solutions contaminated with heavy-metal ions. PMID- 26851360 TI - Chitin and chitosan based polyurethanes: A review of recent advances and prospective biomedical applications. AB - Chitin and chitosan are amino polysaccharides having massive structural propensities to produce bioactive materials with innovative properties, functions and diverse applications particularly in biomedical field. The specific physico chemical, mechanical, biological and degradation properties offer efficient way to blend these biopolymers with synthetic ones. Polyurethane (PU) gained substantial attention owing to its structure-properties relationship. The immense activities of chitin/chitosan are successfully utilized to enhance the bioactive properties of polyurethanes. This review shed a light on chitin and chitosan based PU materials with their potential applications especially focusing the bio medical field. All the technical scientific issues have been addressed highlighting the recent advancement in the biomedical field. PMID- 26851361 TI - The enhanced immune response of PCV-2 vaccine using Rehmannia glutinosa polysaccharide liposome as an adjuvant. AB - Liposomes, one kind of vaccine adjuvants, have been demonstrated as effective adjuvants and vaccine delivery system. Immunization against PCV-2 has been studied intensely and found to be the most effective strategy for protecting pigs against PCV-2 infection. Inactivated vaccines represent a complex mixture of viral antigens closely resembling the native virion. In the present study, PCV-2 attenuated antigen was encapsulated within Rehmannia glutinosa polysaccharide liposome, instead of oil adjuvant which is the mainstream adjuvant. Our results showed that RGPL could elicit a strong IgG response and significantly increased the production of Th1 and Th2 associated IgG subtypes and cytokines. R. glutinosa polysaccharide liposome showed excellent particle stability. In vitro, R. glutinosa polysaccharide liposome could also significantly promote phagocytic activity of macrophage and the levels of cytokines it produced. Overall, the results demonstrated that R. glutinosa polysaccharide liposome has the potential to be developed into a more effective and safer vaccine adjuvant. PMID- 26851362 TI - On the regulatory importance of 27-hydroxycholesterol in mouse liver. AB - 27-Hydroxycholesterol (27OH) is a strong suppressor of cholesterol synthesis and a weak activator of LXR in vitro. The regulatory importance of 27OH in vivo is controversial. Here we utilized male mice with increased levels of 27OH either due to increased production (CYP27A1 transgenic mice) or reduced metabolism (Cyp7b1-/- mice). We also used mice lacking 27OH due to a knockout of Cyp27a1. The latter mice were treated with cholic acid to compensate for reduced bile acid synthesis. The effects of the different levels of 27OH on Srebp- and other LXR regulated genes in the liver were investigated. In the liver of CYP27tg mice we found a modest increase of the mRNA levels corresponding to the LXR target genes Cyp7b1 and Abca1. A number of other LXR-regulated genes were not affected. The effect on Abca1 mRNA was not seen in the liver of Cyp7b1-/- mice. There were little or no effects on cholesterol synthesis. In the liver of the Cyp27-/- mice treated with 0.025% cholic acid there was no significant effect of the knockout on the LXR target genes. In a previous work triple-knockout mice deficient in the biosynthesis of 24S-hydroxycholesterol, 25-hydroxycholesterol and 27OH were shown to have impaired response to dietary cholesterol, suggesting side-chain oxidized oxysterols to be mediators in cholesterol-induced effects on LXR target genes at a transcriptional level (Chen W. et al., Cell Metab. 5 (2007) 73-79). The hydroxylated oxysterol responsible for the effect was not defined. We show here that treatment of wildtype mice with dietary cholesterol under the same conditions as in the above study induced the LXR target genes Lpl, Abcg8 and Srebp1c in wild type mice but failed to activate the same genes in mice lacking 27-hydroxycholesterol due to a knockout of Cyp27. We failed to demonstrate the above effects at the protein level (Abcg8) or at the activity level (Lpl). The results suggest that 27OH is not an important regulator of Srebp- or LXR regulated genes under basal conditions in mouse liver. On the other hand 27OH appears to mediate cholesterol-induced effects on some LXR target genes at a transcriptional level under some in vivo conditions. PMID- 26851363 TI - When I am (almost) 64: The effect of normal ageing on implicit motor imagery in young elderlies. AB - Motor imagery (M.I.) is a cognitive process in which movements are mentally evoked without overt actions. Behavioral and fMRI studies show a decline of explicit M.I. ability (e.g., the mental rehearsal of finger oppositions) with normal ageing: this decline is accompanied by the recruitment of additional cortical networks. However, none of these studies investigated behavioral and the related fMRI ageing modifications in implicit M.I. tasks, like the hand laterality task (HLT). To address this issue, we performed a behavioral and fMRI study: 27 younger subjects (mean age: 31 years) and 29 older subjects (mean age: 61 years) underwent two event-related design fMRI experiments. In the HLT, participants were asked to decide whether a hand rotated at different angles was a left or right hand. To test the specificity of any age related difference in the HLT, we used a letter rotation task as a control experiment: here subjects had to decide whether rotated letters were presented in a standard or a mirror orientation. We did not find any group difference in either behavioral task; however, we found significant additional neural activation in the elderly group in occipito-temporal regions: these differences were stronger for the HLT rather than for the LRT with group by task interactions effects in right occipital cortices. We interpret these results as evidence of compensatory processes associated with ageing that permit a behavioral performance comparable to that of younger subjects. This process appears to be more marked when the task specifically involves motor representations, even when these are implicitly evoked. PMID- 26851364 TI - Long-term heat stress induces the inflammatory response in dairy cows revealed by plasma proteome analysis. AB - In this work we employed a comparative proteomic approach to evaluate seasonal heat stress and investigate proteomic alterations in plasma of dairy cows. Twelve lactating Holstein dairy cows were used and the treatments were: heat stress (n = 6) in hot summer (at the beginning of the moderate heat stress) and no heat stress (n = 6) in spring natural ambient environment, respectively. Subsequently, heat stress treatment lasted 23 days (at the end of the moderate heat stress) to investigate the alterations of plasma proteins, which might be employed as long term moderate heat stress response in dairy cows. Changes in plasma proteins were analyzed by two-dimensional electrophoresis (2-DE) combined with mass spectrometry. Analysis of the properties of the identified proteins revealed that the alterations of plasma proteins were related to inflammation in long-term moderate heat stress. Furthermore, the increase in plasma tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) directly demonstrated that long-term moderate heat stress caused an inflammatory response in dairy cows. PMID- 26851365 TI - OsGF14e positively regulates panicle blast resistance in rice. AB - Though GF14e has been reported to negatively regulate bacterial blight and sheath blight resistance in rice, its effect on panicle blast, the most destructive disease in rice is still unknown. In the present study, we identified that GF14e was highly expressed in panicles and was induced in panicles infected by blast pathogen. Overexpression of GF14e enhances resistance to panicle blast whereas silencing GF14e results in increased susceptibility to panicle blast, suggesting that GF14e plays a positive role in quantitative panicle blast resistance in rice. Our results also demonstrate that GF14e is regulated by WRKY71 and GF14e mediated panicle blast resistance is related to activation of SA-dependent pathway and suppression of JA-dependent pathway. The functional confirmation of GF14e in panicle blast resistance makes it to be a promising target in molecular rice breeding. PMID- 26851366 TI - Proteasomal degradation of damaged polyubiquitin. AB - Ubiquitination is one of the most important post-translational modifications of proteins and is involved in various cellular activities, such as proteasomal protein degradation. Ubiquitination is performed via sequential reactions of three enzymes producing polyubiquitin chains, while deubiquitination enzymes can reverse this process, making it possible to recycle ubiquitin molecules. However, such repeated use may seriously damage ubiquitin molecules and result in cell toxicity. Here we show efficient, selective proteasomal degradation of damaged polyubiquitin chains both in vitro and in vivo. However, the degradation efficiency of the damaged polyubiquitin strongly depends on the extent and location of damage to polyubiquitin. Moderate damage at the C-terminal ubiquitin moiety accelerates the degradation of polyubiquitin chains, whereas other damaged ubiquitin escapes from proteasomal degradation. We suggest that the cell can cope with damaged ubiquitin by the cooperative actions of the proteasome and autophagy. PMID- 26851367 TI - Differentiation of pluripotent stem cells for regenerative medicine. AB - A long-standing goal in regenerative medicine is to obtain scalable functional cells on demand to replenish cells lost in various conditions, including relevant diseases, injuries, and aging. As an unlimited cell source, pluripotent stem cells (PSCs) are invaluable for regenerative medicine, because they have the potential to give rise to any cell type in an organism. For therapeutic purposes, it is important to develop specific approach to directing PSC differentiation towards desired cell types efficiently. Through directed differentiation, PSCs could give rise to scalable, clinically relevant cells for in vivo transplantation, as well as for studying diseases in vitro and discovering drugs to treat them. Over the past few years, significant progress has been made in directing differentiation of PSCs into a variety of cell types. In this review, we discuss recent progress in directed differentiation of PSCs, clinical translation of PSC-based cell replacement therapies, and remaining challenges. PMID- 26851368 TI - Ethambutol neutralizes lysosomes and causes lysosomal zinc accumulation. AB - Ethambutol is a common medicine used for the treatment of tuberculosis, which can have serious side effects, such as retinal and liver dysfunction. Although ethambutol has been reported to impair autophagic flux in rat retinal cells, the precise molecular mechanism remains unclear. Using various mammalian cell lines, we showed that ethambutol accumulated in autophagosomes and vacuolated lysosomes, with marked Zn(2+) accumulation. The enlarged lysosomes were neutralized and were infiltrated with Zn(2+) accumulations in the lysosomes, with simultaneous loss of acidification. These results suggest that EB neutralizes lysosomes leading to insufficient autophagy, implying that some of the adverse effects associated with EB in various organs may be of this mechanism. PMID- 26851369 TI - Predicting delayed kidney graft function with gene expression in preimplantation biopsies and first-day posttransplant blood. AB - The purpose of this study was to investigate possible markers for predicting delayed graft function (DGF). To this end we analyzed, in pre-implantation biopsies (PIB) and in first-day post-Tx peripheral blood mononuclear cells (PBMC), the expression of five genes (ACSL4, CUBN, DEFB1, FABP3, GK) through real time TaqMan PCR assays. These genes were selected from a large scale gene expression study in PIB. DEFB1, FABP3 and GK expression levels in PIB were lower in cases with DGF and, in a multivariate analysis which included these genes and clinical variables, only FABP3 expression remained independently associated with DGF. FABP3 expression lower than -1.32 units of relative expression conferred an odds ratio for DGF of 41.1. Compared to the PBMC of recipients without DGF, recipients with prolonged DGF (pDGF) had lower ACSL4 and higher DEFB1 expression levels. In a multivariate analysis, including PBMC gene expression levels of ACSL4, DEFB1 and TLR4 (data from a previous study with the same patients) and clinical variables, only TLR4 remained independently associated with pDGF. In summary, this study revealed FABP3 expression in PIB as a marker for DGF and disclosed new genes possibly involved in the pathogenesis of DGF. PMID- 26851370 TI - Angiotensin converting enzyme versus angiotensin converting enzyme-2 selectivity of MLN-4760 and DX600 in human and murine bone marrow-derived cells. AB - Angiotensin-converting enzymes, ACE and ACE2, are key members of renin angiotensin system. Activation of ACE2/Ang-(1-7) pathway enhances cardiovascular protective functions of bone marrow-derived stem/progenitor cells. The current study evaluated the selectivity of ACE2 inhibitors, MLN-4760 and DX-600, and ACE and ACE2 activities in human (hu) and murine (mu) bone marrow cells. Assays were carried out in hu and mu mononuclear cells (MNCs) and huCD34(+) cells or mu lineage-depleted (muLin(-)) cells, human-recombinant (rh) enzymes, and mu-heart with enzyme-specific substrates. ACE or ACE2 inhibition by racemic MLN-4760, its isomers MLN-4760-A and MLN-4760-B, DX600 and captopril were characterized. MLN 4760-B is relatively less efficacious and less-selective than the racemate or MLN 4760-A at hu-rhACE2, and all three of them inhibited 43% rhACE. In huMNCs, MLN 4760-B detected 63% ACE2 with 28-fold selectivity over ACE. In huCD34(+) cells, MLN-4760-B detected 38% of ACE2 activity with 63-fold selectivity. In mu-heart and muMNCs, isomer B was 100- and 228-fold selective for ACE2, respectively. In muLin(-) cells, MLN-4760-B detected 25% ACE2 activity with a pIC50 of 6.3. The racemic mixture and MLN-4760-A showed lower efficacy and poor selectivity for ACE2 in MNCs and mu-heart. ACE activity detected by captopril was 32% and 19%, respectively, in huCD34(+) and muLin(-) cells. DX600 was less efficacious, and more selective for ACE2 compared to MLN-4760-B in all samples tested. These results suggest that MLN-4760-B is a better antagonist of ACE2 than DX600 at 10 um concentration in human and murine bone marrow cells, and that these cells express more functional ACE2 than ACE. PMID- 26851371 TI - Taurochenodeoxycholate relaxes rat mesenteric arteries through activating eNOS: Comparing with glycochenodeoxycholate and tauroursodeoxycholate. AB - The bile acids (BAs) and their conjugates have vascular activities and the serum levels of BAs and their conjugates are increased in liver diseases. In the present study, we examined the in vitro vasoactivities of BAs conjugates taurochenodeoxycholate (TCDC) (5-80 uM), glycochenodeoxycholate (GCDC) (20-150 uM) and tauroursodeoxycholate (TUDC) (20-150 uM) in rat mesenteric arteries and thoracic aorta. The isometric tension of rat mesenteric arteries and thoracic aorta was recorded by using multi-wire myograph systems. TCDC induced significant concentration-dependent relaxation in endothelium-intact but not endothelium denuded rat mesenteric arteries pre-contracted with phenylephrine (PE). TCDC also showed vasorelaxant effects on high K(+) induced contraction in rat mesenteric arteries. L-NAME treatment inhibited TCDC-induced relaxation in mesenteric arteries pre-contracted with PE. Acute treatment with TCDC increased protein expression of P-eNOS (ser1177) in human umbilical vein endothelial cells. GCDC dose-dependently relaxed PE-induced vasoconstriction in both endotheium-intact and endothelium-denuded rat mesenteric arteries, but GCDC showed no effect on high K(+)-induced vasoconstriction. Both GCDC and TCDC showed no apparent relaxation on PE and high K(+)-induced vasoconstriction in rat thoracic aorta. TUDC showed no effect on PE and high K(+)-induced vasoconstriction in rat mesenteric arteries and thoracic aorta. The study demonstrates that TCDC relaxes rat mesenteric arteries through activating eNOS. TCDC might be the major BAs conjugate for vasorelaxation in vivo. PMID- 26851372 TI - Bumetanide increases manganese accumulation in the brain of rats with liver damage. AB - Hepatic encephalopathy is a common complication in cases of liver damage; it results from several factors, including the accumulation of toxic substances in the brain, e.g. manganese, ammonia and glutamine. We have previously reported that manganese favors ammonia and glutamine accumulation in the brain of cirrhotic rats, and we suggested that such effect could be mediated by manganese elicited activation of the NKCC1 (Na(+)/K(+)/2Cl(-) cotransporter 1). To test this hypothesis, we used bumetanide, an NKCC1 blocker prescribed to treat ascites in cirrhotic patients; we expected that if NKCC1 was responsible for manganese mediated ammonia buildup and the subsequent glutamine accumulation, bumetanide could counteract such effect and improve motor coordination. In addition, we considered essential to test the effect of bumetanide on manganese brain levels. We used a model of liver damage in rats, consisting in bile-duct ligation. Animals were exposed to manganese in the drinking water (1 mg/ml) for two weeks and ammonia in the food (20% w/w of ammonia acetate) during the second week after surgery. Bumetanide was administered intraperitoneally in the course of the ammonia treatment. We measured glutamine and manganese in three brain regions: frontal cortex, striatum and cerebellum. Bumetanide produced no effect on glutamine accumulation; however, because of bumetanide treatment, manganese was increased in the brain, and also the activity of gamma-glutamyl transferase in plasma; thus, we consider that the influence of bumetanide and similar diuretics on liver function and manganese homeostasis should be further studied. PMID- 26851373 TI - Potassium Transporter KUP7 Is Involved in K(+) Acquisition and Translocation in Arabidopsis Root under K(+)-Limited Conditions. AB - Potassium (K(+)) is one of the essential macronutrients for plant growth and development. K(+) uptake from environment and K(+) translocation in plants are conducted by K(+) channels and transporters. In this study, we demonstrated that KT/HAK/KUP transporter KUP7 plays crucial roles in K(+) uptake and translocation in Arabidopsis root. The kup7 mutant exhibited a sensitive phenotype on low-K(+) medium, whose leaves showed chlorosis symptoms compared with wild-type plants. Loss of function of KUP7 led to a reduction of K(+) uptake rate and K(+) content in xylem sap under K(+)-deficient conditions. Thus, the K(+) content in kup7 shoot was significantly reduced under low-K(+) conditions. Localization analysis revealed that KUP7 was predominantly targeted to the plasma membrane. The complementation assay in yeast suggested that KUP7 could mediate K(+) transport. In addition, phosphorylation on S80, S719, and S721 was important for KUP7 activity. KUP7 was ubiquitously expressed in many organs/tissues, and showed a higher expression level in Arabidopsis root. Together, our data demonstrated that KUP7 is crucial for K(+) uptake in Arabidopsis root and might be also involved in K(+) transport into xylem sap, affecting K(+) translocation from root toward shoot, especially under K(+)-limited conditions. PMID- 26851374 TI - In vitro study of the effect of metabolism enzymes on benzo(a)pyrene-induced DNA damage in the scallop Chlamys farreri. AB - Acute toxicity effect of benzo(a)pyrene (BaP) on isolated scallop (Chlamys farreri) digestive gland cells was studied and a dose-dependent increase in toxicity was observed. The 8 MUg/L of BaP had a significant toxic effect on isolated cells (p<0.05). In order to study the mechanism of CYP450, GST, SOD and MXR transporters involved in the production of DNA strand breakage such as DNA adduct formation and oxidative DNA damage by BaP were investigated in isolated digestive gland cells. Isolated cells were exposed in vitro to 0.8 MUg/L of BaP for 24h in the dark at 25 degrees C in the absence or presence of cytochrome P450 inhibitor, GST inhibitor, Pgp inhibitor and antioxidant enzyme inhibitor. DNA adduct and 8-OHdG content were measured using the Enzyme-linked Immunosorbent Assay. The result indicated that DNA strand breakage was increased to 2 times compared with the control in the 0.8 MUg/L of BaP treatment groups. The BaP induced DNA adduct and 8-OHdG content increased significantly by inhibiting GST, while only 8-OHdG increased significantly when SOD was inhibited. The content of DNA adduct and 8-OHdG had no significant change when CYP450 was inhibited, while it decreased significantly when MXR transporters were inhibited. The result proved that GST play a key role in eliminating the BaP-induced DNA adduct and 8 OHdG, and SOD also had an important function in reducing the production of BaP induced 8-OHdG. PMID- 26851375 TI - Pretilachlor has the potential to induce endocrine disruption, oxidative stress, apoptosis and immunotoxicity during zebrafish embryo development. AB - The objectives of the present study were to investigate the toxic effects of pretilachlor on zebrafish during its embryo development. The results demonstrated that the transcription of genes involved in the hypothalamic-pituitary gonadal/thyroid (HPG/HPT) axis was increased after exposure to 50, 100, 200 MUg/L pretilachlor for 96 h, the aromatase activity, vitellogenin (VTG) and thyroid hormones T3 and T4 levels in zebrafish were also up-regulated simultaneously. Pretilachlor exposure induced a noticeable increase in ROS level, increased the transcription and level of antioxidant proteins (e.g., CAT, SOD and GPX). Moreover, the up-regulation of P53, Mdm2, Bbc3 expression and Caspase3 and Caspase9 activities in the apoptosis pathway suggested pretilachlor might trigger cell apoptosis in zebrafish. In addition, the transcription of CXCL-C1C, IL-1beta and IL-8 related to the innate immunity was down-regulated after pretilachlor exposure. These data suggested that pretilachlor could simultaneously induce endocrine disruption, apoptosis, oxidative stress and immunotoxicity during zebrafish embryo development. PMID- 26851376 TI - Building up a QSAR model for toxicity toward Tetrahymena pyriformis by the Monte Carlo method: A case of benzene derivatives. AB - Data on toxicity toward Tetrahymena pyriformis is indicator of applicability of a substance in ecologic and pharmaceutical aspects. Quantitative structure-activity relationships (QSARs) between the molecular structure of benzene derivatives and toxicity toward T. pyriformis (expressed as the negative logarithms of the population growth inhibition dose, mmol/L) are established. The available data were randomly distributed three times into the visible training and calibration sets, and invisible validation sets. The statistical characteristics for the validation set are the following: r(2)=0.8179 and s=0.338 (first distribution); r(2)=0.8682 and s=0.341 (second distribution); r(2)=0.8435 and s=0.323 (third distribution). These models are built up using only information on the molecular structure: no data on physicochemical parameters, 3D features of the molecular structure and quantum mechanics descriptors are involved in the modeling process. PMID- 26851377 TI - Zearalenone impairs the male reproductive system functions via inducing structural and functional alterations of sertoli cells. AB - The aim of this study was to investigate the effects of ZEA on the cytoskeletal structure, and factors specifically expressed by Sertoli cells. Primary Sertoli cells from rats aged 18-21 days were exposed to increasing ZEA concentrations (0, 5, 10, 20 MUg mL(-1)) for 24 h. The results of immunofluorescence showed disruption of alpha-tubulin filaments and F-actin bundles, and damage to the nucleus of Sertoli cells on exposure to ZEA. In the control group, the protein level expression of androgen-binding protein (ABP), transferrin, vimentin, N cadherin, and follicle-stimulating hormone receptor (FSHR) were decreased significantly (p<0.05, p<0.01). The mRNA levels of ABP, transferrin, vimentin, N cadherin, and FSHR varied significantly in the experimental group (p<0.05). The results of enzyme-linked immunosorbent assay indicated a significant decrease in the levels of inhibin-beta and transferrin in the cultural supernatants (p<0.05). Additionally, the ultrastructural analysis indicated the absence of mitochondria and Golgi apparatus, and presence of vacuoles in the cytoplasm. These findings showed that ZEA treatment can damage the cytoskeletal structure and affect specific secretory functions of Sertoli cells, which may be an underlying cause of ZEA-induced reproductive toxicity. PMID- 26851379 TI - Development and evaluation of an automated fall risk assessment system. AB - BACKGROUND AND OBJECTIVE: Fall risk assessment is the first step toward prevention, and a risk assessment tool with high validity should be used. This study aimed to develop and validate an automated fall risk assessment system (Auto-FallRAS) to assess fall risks based on electronic medical records (EMRs) without additional data collected or entered by nurses. METHODS: This study was conducted in a 1335-bed university hospital in Seoul, South Korea. The Auto FallRAS was developed using 4211 fall-related clinical data extracted from EMRs. Participants included fall patients and non-fall patients (868 and 3472 for the development study; 752 and 3008 for the validation study; and 58 and 232 for validation after clinical application, respectively). The system was evaluated for predictive validity and concurrent validity. RESULTS: The final 10 predictors were included in the logistic regression model for the risk-scoring algorithm. The results of the Auto-FallRAS were shown as high/moderate/low risk on the EMR screen. The predictive validity analyzed after clinical application of the Auto FallRAS was as follows: sensitivity = 0.95, NPV = 0.97 and Youden index = 0.44. The validity of the Morse Fall Scale assessed by nurses was as follows: sensitivity = 0.68, NPV = 0.88 and Youden index = 0.28. CONCLUSION: This study found that the Auto-FallRAS results were better than were the nurses' predictions. The advantage of the Auto-FallRAS is that it automatically analyzes information and shows patients' fall risk assessment results without requiring additional time from nurses. PMID- 26851378 TI - Brain Aggregates: An Effective In Vitro Cell Culture System Modeling Neurodegenerative Diseases. AB - Drug discovery for neurodegenerative diseases is particularly challenging because of the discrepancies in drug effects between in vitro and in vivo studies. These discrepancies occur in part because current cell culture systems used for drug screening have many limitations. First, few cell culture systems accurately model human aging or neurodegenerative diseases. Second, drug efficacy may differ between dividing and stationary cells, the latter resembling nondividing neurons in the CNS. Brain aggregates (BrnAggs) derived from embryonic day 15 gestation mouse embryos may represent neuropathogenic processes in prion disease and reflect in vivo drug efficacy. Here, we report a new method for the production of BrnAggs suitable for drug screening and suggest that BrnAggs can model additional neurological diseases such as tauopathies. We also report a functional assay with BrnAggs by measuring electrophysiological activities. Our data suggest that BrnAggs could serve as an effective in vitro cell culture system for drug discovery for neurodegenerative diseases. PMID- 26851380 TI - Mediator Architecture and RNA Polymerase II Interaction. AB - Integrated structural biology recently elucidated the architecture of Mediator and its position on RNA polymerase II. Here we summarize these achievements and list open questions on Mediator structure and mechanism. PMID- 26851383 TI - Walking-induced muscle fatigue impairs postural control in adolescents with unilateral spastic cerebral palsy. AB - BACKGROUND: Fatigue is likely to be an important limiting factor in adolescents with spastic cerebral palsy (CP). AIMS: To determine the effects of walking induced fatigue on postural control adjustments in adolescents with unilateral CP and their typically developing (TD) peers. METHODS: Ten adolescents with CP (14.2 +/- 1.7 yr) and 10 age-, weight- and height-matched TD adolescents (14.1 +/- 1.9 yr) walked for 15 min on a treadmill at their preferred walking speed. Before and after this task, voluntary strength capacity of knee extensors (MVC) and postural control were evaluated in 3 conditions: eyes open (EO), eyes closed (EC) and with dual cognitive task (EODT). RESULTS: After walking, MVC decreased significantly in CP (-11%, P<0.05) but not in TD. The CoP area was only significantly increased in CP (90%, 34% and 60% for EO, EC and EODT conditions, respectively). The CoP length was significantly increased in the EO condition in CP and TD (20% and 21%) and was significantly increased in the EODT condition by 18% in CP only. CONCLUSIONS: Unlike TD adolescents, treadmill walking for 15 min at their preferred speed lead to significant knee extensor strength losses and impairments in postural control in adolescents with unilateral spastic CP. PMID- 26851381 TI - Moving towards personalised therapy in head and neck squamous cell carcinoma through analysis of next generation sequencing data. AB - Personalised medicine tumour boards, which leverage genomic data to improve clinical management, are becoming standard for the treatment of many cancers. This paper is designed as a primer to assist clinicians treating head and neck squamous cell carcinoma (HNSCC) patients with an understanding of the discovery and functional impact of recurrent genetic lesions that are likely to influence the management of this disease in the near future. This manuscript integrates genetic data from publicly available array comparative genome hybridization (aCGH) and next-generation sequencing genetics databases to identify the most common molecular alterations in HNSCC. The importance of these genetic discoveries is reviewed and how they may be incorporated into clinical care decisions is discussed. Considerations for the role of genetic stratification in the clinical management of head and neck cancer are maturing rapidly and can be improved by integrating data sets. This article is meant to summarise the discoveries made using multiple genomic platforms so that the head and neck cancer care provider can apply these discoveries to improve clinical care. PMID- 26851384 TI - The interrelationships between motor, cognitive, and language development in children with and without intellectual and developmental disabilities. AB - It is generally agreed that cognitive and language development are dependent on the emergence of motor skills. As the literature on this issue concerning children with developmental disabilities is scarce, we examined the interrelationships between motor, cognitive, and language development in children with intellectual and developmental disabilities (IDD) and compared them to those in children without IDD. In addition, we investigated whether these relationships differ between children with different levels of cognitive delay. Seventy-seven children with IDD (calendar age between 1;0 and 9;10 years; mean developmental age: 1;8 years) and 130 typically developing children (calendar age between 0;3 and 3;6 years; mean developmental age: 1;10 years) were tested with the Dutch Bayley Scales of Infant and Toddler Development, Third Edition, which assesses development across three domains using five subscales: fine motor development, gross motor development (motor), cognition (cognitive), receptive communication, and expressive communication (language). Results showed that correlations between the motor, cognitive, and language domains were strong, namely .61 to .94 in children with IDD and weak to strong, namely .24 to .56 in children without IDD. Furthermore, the correlations showed a tendency to increase with the severity of IDD. It can be concluded that both fine and gross motor development are more strongly associated with cognition, and consequently language, in children with IDD than in children without IDD. The findings of this study emphasize the importance of early interventions that boost both motor and cognitive development, and suggest that such interventions will also enhance language development. PMID- 26851382 TI - Hypolipidemic potential of perillaldehyde-loaded self-nanoemulsifying delivery system in high-fat diet induced hyperlipidemic mice: Formulation, in vitro and in vivo evaluation. AB - This study reports the hypolipidemic effects of perillaldehyde-loaded self nanoemulsifying delivery system (PAH-SNEDS) developed with D-optimal experimental design based on a three component system: 40% w/w drug-oil phase, X1 (a mixture of perillaldehyde-isopropyl myristate/medium chain triglyceride, 1:1, w/w); 48% surfactant, X2 (Kolliphor EL); and 12% co-surfactant, X3 (PEG 200). The design space was navigated using a linear model to produce spherical and homogenous droplets which were observed under TEM, with mean size, polydispersity index (PDI) and zeta potential of 32.8 +/- 0.1 nm, 0.270 +/- 0.029 and -10.14 +/- 0.66 mV, respectively. PAH-SNEDS demonstrated significant increase in dissolution in vitro compared to the free PAH, and further yielded an oral relative bioavailability of about 206.18% in vivo which suggested a promising formulation design for potential liquid bioactive compounds. Oral administration of PAH-SNEDS (240 mg/kg per body weight) in high-fat induced hyperlipidemia in mice, also significantly decreased serum total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) while increasing high-density lipoprotein cholesterol (HDL-C) level. The improved bioavailability and functional application of PAH via SNEDDS suggested a suitable approach to promote hypolipidemic effect of the drug. Perillaldehyde, therefore, promises to be a useful bioactive compound to prevent high-fat diet induced hyperlipidemia. PMID- 26851385 TI - A pilot study on early home-based intervention through an intelligent baby gym (CareToy) in preterm infants. AB - BACKGROUND: CareToy is an intelligent system, inspired by baby gyms, aimed to provide an intensive, individualized, home-based and family-centred early intervention (EI) program. AIMS: A pilot study was carried out to explore the feasibility of CareToy intervention in preterm infants, aged 3-9 months of corrected age. METHODS: Twenty low-risk preterm infants, without brain lesion or other clinical complications (14 allocated to CareToy intervention and 6 to Standard Care) were recruited. The Infant Motor Profile (IMP) was predefined as the primary outcome measure and Alberta Infant Motor Scale and Teller Acuity Cards as secondary measures. Moreover, 202 pre-programmed training scenarios were developed and instructions for the management of CareToy intervention were defined as general guidelines. OUTCOMES AND RESULTS: All infants received 4 weeks of their allocated intervention and were evaluated with the selected tests before and immediately after the 4 weeks. The mean difference changes in IMP total score and Teller Acuity Cards over the intervention period were higher in the CareToy group than in the Standard Care group. CONCLUSIONS AND IMPLICATIONS: CareToy seems a feasible device for providing EI. An adequately powered randomized clinical trial is warranted. PMID- 26851386 TI - Do "Consumer-Directed" health plans bend the cost curve over time? AB - "Consumer-Directed" Health Plans (CDHPs), those with high deductibles and personal medical accounts, are intended to reduce health care spending through greater patient cost exposure. Prior research agrees that in the first year, CDHPs reduce spending. There is little research and in it results are mixed regarding the impact of CDHPs over the longer term. We add to this literature with an intent-to-treat, difference-in-differences analysis of health care spending over up to three years post CDHP offer among 13 million person-years of data from 54 large US firms, half of which offered CDHPs. To strengthen the identification, we balance observables over time within firm, by developing weights through a machine learning algorithm, generalized boosted regression. We find that spending is reduced for those in firms offering CDHPs in all three years post offer relative to firms continuing to offer lower-deductible plans. The reductions are driven by spending decreases in outpatient care and pharmaceuticals, with no evidence of increases in emergency department or inpatient care over the three-year window. PMID- 26851387 TI - Complete genome sequence of Streptomyces reticuli, an efficient degrader of crystalline cellulose. AB - We report the complete, GC-rich genome sequence of the melanin producer Streptomyces reticuli Tu 45 (S. reticuli) that targets and degrades highly crystalline cellulose by the concerted action of a range of biochemically characterized proteins. It consists of a linear 8.3 Mb chromosome, a linear 0.8 Mb megaplasmid, a linear 94 kb plasmid and a circular 76 kb plasmid. Noteworthy, the megaplasmid is the second largest known Streptomyces plasmid. Preliminary analysis reveals, among others, 43 predicted gene clusters for the synthesis of secondary metabolites and 456 predicted genes for binding and degradation of cellulose, other polysaccharides and carbohydrate-containing compounds. PMID- 26851388 TI - Draft genome sequence of the sugar beet pathogen Rhizoctonia solani AG2-2IIIB strain BBA69670. AB - Rhizoctonia solani is a widespread plant pathogenic fungus featuring a broad host range including several economically important crops. Accordingly, genome analyses of R. solani isolates are important to uncover their pathogenic potential. Draft genome sequences for four R. solani isolates representing three of the 14 R. solani anastomosis groups (AGs) are available. Here, we present the first draft genome sequence for an R. solani AG2-2IIIB isolate that is pathogenic on sugar beet. The fungal genome was assembled in 2065 scaffolds consisting of 5826 contigs amounting to a size of about 52 Mb which is larger than any other R. solani isolate known today. Genes potentially encoding cellulolytic, lignolytic and pectinolytic enzymes were identified. PMID- 26851390 TI - Hyaluronic acid-shelled acid-activatable paclitaxel prodrug micelles effectively target and treat CD44-overexpressing human breast tumor xenografts in vivo. AB - The therapeutic efficacy of nanoscale anticancer drug delivery systems is severely truncated by their low tumor-targetability and inefficient drug release at the target site. Here, we report the design and development of novel endosomal pH-activatable paclitaxel prodrug micelles based on hyaluronic acid-b-dendritic oligoglycerol (HA-dOG-PTX-PM) for active targeting and effective treatment of CD44-overexpressing human breast cancer xenografts in nude mice. HA-dOG-PTX-PM had a high drug content of 20.6 wt.% and an average diameter of 155 nm. The release of PTX was slow at pH 7.4 but greatly accelerated at endosomal pH. MTT assays, flow cytometry and confocal experiments showed that HA-dOG-PTX-PM possessed a high targetability and antitumor activity toward CD44 receptor overexpressing MCF-7 human breast cancer cells. The in vivo pharmacokinetics and biodistribution studies showed that HA-dOG-PTX-PM had a prolonged circulation time in the nude mice and a remarkably high accumulation in the MCF-7 tumor (6.19%ID/g at 12 h post injection). Interestingly, HA-dOG-PTX-PM could effectively treat mice bearing MCF-7 human breast tumor xenografts with little side effects, resulting in complete inhibition of tumor growth and a 100% survival rate over an experimental period of 55 days. These results indicate that hyaluronic acid-shelled acid-activatable PTX prodrug micelles have a great potential for targeted chemotherapy of CD44-positive cancers. PMID- 26851391 TI - The two faces of metal ions: From implants rejection to tissue repair/regeneration. AB - The paradigm of metallic ions as exclusive toxic agents is changing. During the last 60 years, knowledge about toxicological and immunological reactions to metal particles and ions has advanced considerably. Hip prostheses, namely metal-on metal bearings, have prompted studies about excessive and prolonged exposure to prosthetic debris. In that context, the interactions of metal particles and ions with cells and tissues are mostly harmful, inducing immune responses that lead to osteolysis and implant failure. However, in the last decade, new strategies to promote immunomodulation and healing have emerged based on the unique properties of metallic ions. The atom-size and charge enable ions to interact with key macromolecules (e.g. proteins, nucleic acids) that affect cellular function. Moreover, these agents are inexpensive, stable and can be integrated in biomaterials, which may open new avenues for a novel generation of medical devices. Herein, orthopedic devices are discussed as models for adverse responses to metal ions, and debated together with the potential to use metal ions-based therapies, thus bridging the gap between unmet clinical needs and cutting-edge research. In summary, this review addresses the two "faces" of metallic ions, from pathological responses to innovative research strategies that use metal ions for regenerative medicine. PMID- 26851389 TI - Placental membrane aging and HMGB1 signaling associated with human parturition. AB - Aging is associated with the onset of several diseases in various organ systems; however, different tissues may age differently, rendering some of them dysfunctional sooner than others. Placental membranes (fetal amniochorionic membranes) protect the fetus throughout pregnancy, but their longevity is limited to the duration of pregnancy. The age-associated dysfunction of these membranes is postulated to trigger parturition. Here, we investigated whether cellular senescence-the loss of cell division potential as a consequence of stress-is involved in placental membrane function at term. We show telomere reduction, p38 MAPK activation, increase in p21 expression, loss of lamin B1 loss, increase in SA-beta-galactosidase , and senescence-associated secretory phenotype (SASP) gene expression in placental membranes after labor and delivery (term labor [TL]) compared to membranes prior to labor at term (term, not-in-labor [TNIL]). Exposing TNIL placental membranes to cigarette smoke extract, an oxidative stress inducer, also induced markers of cellular senescence similar to those in TL placental membranes. Bioinformatics analysis of differentially expressed SASP genes revealed HMGB1 signaling among the top pathways involved in labor. Further, we show that recombinant HMGB1 upregulates the expression of genes associated with parturition in myometrial cells. These data suggest that the natural physiologic aging of placental tissues is associated with cellular senescence and human parturition. PMID- 26851392 TI - Design and evaluation of novel pH-sensitive ureido-conjugated chitosan/TPP nanoparticles targeted to Helicobacter pylori. AB - The covalently modified ureido-conjugated chitosan/TPP multifunctional nanoparticles have been developed as targeted nanomedicine delivery system for eradication of Helicobacter pylori. H. pylori can specifically express the urea transport protein on its membrane to transport urea into cytoplasm for urease to produce ammonia, which protects the bacterium in the acid milieu of stomach. The clinical applicability of topical antimicrobial agent is needed to eradicate H. pylori in the infected fundal area. In this study, we designed and synthesized two ureido-conjugated chitosan derivatives UCCs-1 and UCCs-2 for preparation of multifunctional nanoparticles. The process was optimized in order to prepare UCCs/TPP nanoparticles for encapsulation of amoxicillin. The results showed that the amoxicillin-UCCs/TPP nanoparticles exhibited favorable pH-sensitive characteristics, which could procrastinate the release of amoxicillin at gastric acids and enable the drug to deliver and target to H. pylori at its survival region effectively. Compared with unmodified amoxicillin-chitosan/TPP nanoparticles, a more specific and effective H. pylori growth inhibition was observed for amoxicillin-UCCs/TPP nanoparticles. Drug uptake analysis tested by flow cytometry and confocal laser scanning microscopy verified that the uptake of FITC-UCCs-2/TPP nanoparticles was associated with urea transport protein on the membrane of H. pylori and reduced with the addition of urea as competitive transport substrate. These findings suggest that the multifunctional amoxicillin loaded nanoparticles have great potential for effective therapy of H. pylori infection. They may also serve as pharmacologically effective nanocarriers for oral targeted delivery of other therapeutic drugs to treat H. pylori. PMID- 26851393 TI - Systemic administration of RANKL overcomes the bottleneck of oral vaccine delivery through microfold cells in ileum. AB - A successful delivery of antigen through oral route requires to overcome several barriers, such as enzymatic barrier of gastrointestinal tract and epithelial barrier that constitutes of microfold cells (M cells) for antigen uptake. Although each barrier represents a critical step in determining the final efficiency of antigen delivery, the transcytosis of antigen by M cells in the follicle-associated epithelium (FAE) to Peyer's patches appears to be a major bottleneck. Considering the systemic administration of receptor activator of nuclear factor (NF)-KB ligand (RANKL) induces differentiation of receptor activator of nuclear factor (NF)-KB (RANK)-expressing enterocytes into M cells, here, we illustrated a promising approach of antigen delivery using full length transmembrane RANKL (mRANKL). The results showed that the intraperitoneal injection of mRANKL increased the population of dendritic cells and macrophages in mesenteric lymph nodes and spleen. Subsequently, systemic administration of mRANKL resulted in significantly higher number of functional GP2(+) M cells leading higher transcytosis of fluorescent beads through them. To corroborate the effect of mRANKL in antigen delivery through M cells, we orally delivered microparticulate antigen to mice treated with mRANKL. Oral immunization induced strong protective IgA and systemic IgG antibody responses against orally delivered antigen in mRANKL-treated mice. The higher antibody responses are attributed to the higher transcytosis of antigens through M cells. Ultimately, the higher memory B cells and effector memory CD4 T cells after oral immunization in RANKL-treated mice confirmed potency of RANKL-mediated antigen delivery. To the best of our knowledge, this is the first study to demonstrate significant induction of mucosal and humoral immune responses to M cell targeted oral vaccines after the systemic administration of RANKL. PMID- 26851395 TI - Two cases of cisplatin-induced permanent renal failure following neoadjuvant chemotherapy for esophageal cancer. AB - INTRODUCTION: We experienced two esophageal cancer patients who developed severe acute renal failure after neoadjuvant chemotherapy with cisplatin and 5 fluorourasil. PRESENTATION OF CASE: After administration of cisplatin, their serum creatinine increased gradually until they required hemodialysis and their renal failure was permanent. In both cases, renal biopsy examination indicated partial recovery of the proximal tubule, but renal function did not recover. After these events, one patient underwent definitive radiotherapy and the other underwent esophagectomy for their esophageal cancers, while continuing dialysis. Both patients are alive without cancer recurrence. DISCUSSION: In these two cases of cisplatin-induced renal failure, renal biopsy examination showed only slight disorder of proximal tubules and tendency to recover. CONCLUSION: Although cisplatin-related nephrotoxicity is a well-recognized complication, there have been few reports of renal failure requiring hemodialysis in cancer patients. In this report, we present their clinical courses and the pathological findings of cisplatin-related renal failure. PMID- 26851396 TI - Time discounting, present biases, and health-related behaviors: Evidence from Japan. AB - Human health is considered the outcome of intertemporal choices under tradeoffs between a small immediate reward and a larger delayed reward. Health-related behaviors are thus affected by personal time preferences. Based on an Internet based survey conducted on Japanese adults, we contribute to the literature by incorporating the multifaceted nature of time discounting in an analysis of the associations between time preference and health-related behaviors. We find that, first, less patient respondents tend to exhibit worse health-related attributes. Second, present bias, which is measured by the degree of declining impatience, is positively associated with unhealthy behaviors for naive respondents, who are unaware of their self-control problem. Third, such associations cannot be found in sophisticates, who are aware of that. As a policy implication, direct intervention policies, including "nudging," are more effective than a commitment device provision in correcting the unhealthy behaviors due to present bias. Fourth, the sign effect, wherein future losses are discounted at a lower rate than future gains, is negatively associated with unhealthy outcomes, although at weak statistical significance levels. PMID- 26851394 TI - Multifunctional coatings to simultaneously promote osseointegration and prevent infection of orthopaedic implants. AB - The two leading causes of failure for joint arthroplasty prostheses are aseptic loosening and periprosthetic joint infection. With the number of primary and revision joint replacement surgeries on the rise, strategies to mitigate these failure modes have become increasingly important. Much of the recent work in this field has focused on the design of coatings either to prevent infection while ignoring bone mineralization or vice versa, to promote osseointegration while ignoring microbial susceptibility. However, both coating functions are required to achieve long-term success of the implant; therefore, these two modalities must be evaluated in parallel during the development of new orthopaedic coating strategies. In this review, we discuss recent progress and future directions for the design of multifunctional orthopaedic coatings that can inhibit microbial cells while still promoting osseointegration. PMID- 26851397 TI - Current standards and new innovative approaches for treatment of pancreatic cancer. AB - Pancreatic adenocarcinoma remains a devastating disease with a 5-year survival rate not exceeding 6%. Treatment of this disease remains a major challenge. This article reviews the state-of-the-art in the management of this disease and the new innovative approaches that may help to accelerate progress in treating its victims. After careful pre-therapeutic evaluation, only 15-20% of patients diagnosed with a pancreatic cancer (PC) are eligible for upfront radical surgery. After R0 or R1 resection in such patients, evidence suggests a significantly positive impact on survival of adjuvant chemotherapy comprising 6 months of gemcitabine or fluorouracil/folinic acid. Delayed adjuvant chemoradiation is considered as an option in cases of positive margins. Borderline resectable pancreatic cancer (BRPC) is defined as a tumour involving the mesenteric vasculature to a limited extend. Resection of these tumours is technically feasible, yet runs the high risk of a R1 resection. Neoadjuvant treatment probably offers the best chance of achieving successful R0 resection and long term survival, but the best treatment options should be determined in prospective randomised studies. Gemcitabine has for 15 years been the only validated therapy for advanced PC. Following decades of negative phase III studies, increasing evidence now suggests that further significant improvements to overall survival can be achieved via either Folfirinox or gemcitabine + nab-paclitaxel regimens. Progress in systemic therapy may improve the chances of resection in borderline resectable pancreatic cancer (BRPC) or locally advanced PC. This requires first enhancing knowledge of the genetic events driving carcinogenesis, which may then be translated into clinical studies. PMID- 26851398 TI - Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy. AB - OBJECTIVE: Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in randomized, double-blind trials. This analysis explored the efficacy and safety of rolapitant in preventing CINV over multiple cycles of MEC or HEC. PATIENTS AND METHODS: Patients in one phase III MEC, one phase II HEC, and two phase III HEC clinical trials were randomized to receive oral rolapitant (180 mg) or placebo in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Regardless of response in cycle 1, patients could continue the same antiemetic treatment for up to six cycles. On days 6-8 of each subsequent chemotherapy cycle, patients reported the incidence of emesis and/or nausea interfering with normal daily life. Post hoc analyses of pooled safety and efficacy data from the four trials were performed for cycles 2-6. RESULTS: Significantly more patients receiving rolapitant than control reported no emesis or interfering nausea (combined measure) in cycles 2 (p = 0.006), 3 (p < 0.001), 4 (p = 0.001), and 5 (p = 0.021). Over cycles 1-6, time-to-first emesis was significantly longer with rolapitant than with control (p < 0.001). The incidence of treatment-related adverse events during cycles 2-6 was similar in rolapitant (5.5%) and control (6.8%) arms. No cumulative toxicity was observed. CONCLUSIONS: Over multiple cycles of MEC or HEC, rolapitant provided superior CINV protection and reduced emesis and nausea interfering with daily life compared with control and remained well tolerated. PMID- 26851400 TI - Software tools for simultaneous data visualization and T cell epitopes and disorder prediction in proteins. AB - We have developed EpDis and MassPred, extendable open source software tools that support bioinformatic research and enable parallel use of different methods for the prediction of T cell epitopes, disorder and disordered binding regions and hydropathy calculation. These tools offer a semi-automated installation of chosen sets of external predictors and an interface allowing for easy application of the prediction methods, which can be applied either to individual proteins or to datasets of a large number of proteins. In addition to access to prediction methods, the tools also provide visualization of the obtained results, calculation of consensus from results of different methods, as well as import of experimental data and their comparison with results obtained with different predictors. The tools also offer a graphical user interface and the possibility to store data and the results obtained using all of the integrated methods in the relational database or flat file for further analysis. The MassPred part enables a massive parallel application of all integrated predictors to the set of proteins. Both tools can be downloaded from http://bioinfo.matf.bg.ac.rs/home/downloads.wafl?cat=Software. Appendix A includes the technical description of the created tools and a list of supported predictors. PMID- 26851399 TI - Relationship between imatinib trough concentration and outcomes in the treatment of advanced gastrointestinal stromal tumours in a real-life setting. AB - BACKGROUND: Imatinib has dramatically improved the prognosis of advanced gastrointestinal stromal tumours (GISTs). Clinical trial data showed that patients with trough imatinib plasma concentrations (Cmin) below 1100 ng/ml (quartile 1) had shorter time to progression, but no threshold has been defined. The main objective of this study was to investigate in advanced GIST whether a Cmin threshold value associated with a longer progression-free survival (PFS) could be specified. This would be the first step leading to therapeutic drug monitoring of imatinib in GIST. PATIENTS AND METHODS: Advanced GIST patients (n=96) treated with imatinib 400 mg/d (41 stomach, 34 small bowel, and 21 other primary site localisations) were prospectively included in this real-life setting study. Routine plasma level testing imatinib (Cmin) and clinical data of were recorded prospectively. RESULTS: Small bowel localisation was associated with an increased relative risk of progression of 3.09 versus stomach localisation (p=0.0255). Mean Cmin (+/-standard deviation) was 868 (+/-536) ng/ml with 75% inter-individual and 26% intra-patient variability. A Cmin threshold of 760 ng/ml defined by log-rank test was associated with longer PFS for the whole population (p=0.0256) and for both stomach (p=0.043) and small bowel (p=0.049) localisations when analysed separately. Multivariate Cox regression analysis found that Cmin above 760 ng/ml was associated with 65% reduction risk of progression (p=0.0271) in the whole population independently of the anatomical localisation. CONCLUSION: Concentration of imatinib significantly influences duration of tumour control treatment in GIST patients with a Cmin threshold of 760 ng/ml associated with prolonged PFS in real-life setting. PMID- 26851401 TI - Prediction of black box warning by mining patterns of Convergent Focus Shift in clinical trial study populations using linked public data. AB - OBJECTIVE: To link public data resources for predicting post-marketing drug safety label changes by analyzing the Convergent Focus Shift patterns among drug testing trials. METHODS: We identified 256 top-selling prescription drugs between 2003 and 2013 and divided them into 83 BBW drugs (drugs with at least one black box warning label) and 173 ROBUST drugs (drugs without any black box warning label) based on their FDA black box warning (BBW) records. We retrieved 7499 clinical trials that each had at least one of these drugs for intervention from the ClinicalTrials.gov. We stratified all the trials by pre-marketing or post marketing status, study phase, and study start date. For each trial, we retrieved drug and disease concepts from clinical trial summaries to model its study population using medParser and SNOMED-CT. Convergent Focus Shift (CFS) pattern was calculated and used to assess the temporal changes in study populations from pre-marketing to post-marketing trials for each drug. Then we selected 68 candidate drugs, 18 with BBW warning and 50 without, that each had at least nine pre-marketing trials and nine post-marketing trials for predictive modeling. A random forest predictive model was developed to predict BBW acquisition incidents based on CFS patterns among these drugs. Pre- and post-marketing trials of BBW and ROBUST drugs were compared to look for their differences in CFS patterns. RESULTS: Among the 18 BBW drugs, we consistently observed that the post-marketing trials focused more on recruiting patients with medical conditions previously unconsidered in the pre-marketing trials. In contrast, among the 50 ROBUST drugs, the post-marketing trials involved a variety of medications for testing their associations with target intervention(s). We found it feasible to predict BBW acquisitions using different CFS patterns between the two groups of drugs. Our random forest predictor achieved an AUC of 0.77. We also demonstrated the feasibility of the predictor for identifying long-term BBW acquisition events without compromising prediction accuracy. CONCLUSIONS: This study contributes a method for post-marketing pharmacovigilance using Convergent Focus Shift (CFS) patterns in clinical trial study populations mined from linked public data resources. These signals are otherwise unavailable from individual data resources. We demonstrated the added value of linked public data and the feasibility of integrating ClinicalTrials.gov summaries and drug safety labels for post-marketing surveillance. Future research is needed to ensure better accessibility and linkage of heterogeneous drug safety data for efficient pharmacovigilance. PMID- 26851402 TI - CaTip41 regulates protein phosphatase 2A activity, CaRad53 deactivation and the recovery of DNA damage-induced filamentation to yeast form in Candida albicans. AB - Phosphorylation and dephosphorylation of the checkpoint kinase CaRad53 is crucial for fungal cells in response to genotoxic stresses. The protein phosphatase 2A (PP2A) CaPph3/CaPsy2 phosphatase complex is involved in CaRad53 dephosphorylation in Candida albicans. In view of the role of ScTip41/ScTap42 in regulating PP2A phosphatases in Saccharomyces cerevisiae, we have explored the function of CaTip41 in C. albicans. Here, we show that CaTIP41 is a functional ortholog of ScTIP41 in the sensitivity of S. cerevisiae cells to rapamycin. Deletion of CaTIP41 causes C. albicans cells to be sensitive to DNA damaging agents, methylmethane sulfonate (MMS) and cisplatin, and resistant to both rapamycin and caffeine. Accordingly, expression of CaTip41 increases in response to MMS and cisplatin. In addition, C. albicans cells lacking CaTIP41 show a delay in the recovery from MMS-induced filamentation to yeast form, decreased PP2A activity and a defect in deactivation of CaRad53 during recovery from DNA damage. Through yeast two-hybrid assay we show that CaTip41 interacts with either CaPph3, CaPsy2 or CaTap42. Therefore, CaTip41 plays regulatory roles in both the CaRad53 deactivation during recovery from DNA damage and the target of rapamycin signaling pathway. PMID- 26851403 TI - Absence of Rtt109p, a fungal-specific histone acetyltransferase, results in improved acetic acid tolerance of Saccharomyces cerevisiae. AB - RTT109 is a histone acetyltransferase for the acetylation of histone H3. It is still not clear whether RTT109 plays a role in regulation of gene expression under environmental stresses. In this study, the involvement of RTT109 in acetic acid stress tolerance of Saccharomyces cerevisiae was investigated. It was revealed that the absence of RTT109 enhanced resistance to 5.5 g L(-1) acetic acid, which was indicated by improved growth of RTT109Delta mutant compared with that of the wild-type BY4741 strain. Meanwhile, the lag phase was shortened for 48 h and glucose consumption completed 36 h in advance for RTT109Delta mutant compared to the wild-type strain, with ethanol production rate increased from 0.39 to 0.60 g L(-1) h(-1). Significantly, elevated transcription levels of HSP12, CTT1 and GSH1, as well as increased activities of antioxidant enzymes were observed in RTT109Delta under acetic acid stress. Improved flocculation of RTT109Delta compared to that of the control strain BY4741 under the acetic acid stress was also observed. These results suggest that the absence of RTT109 not only activates transcription of stress responsive genes, but also improves resistance to oxidative stress, which ultimately contributes to improved acetic acid tolerance in S. cerevisiae. PMID- 26851405 TI - Vision, knowledge, and assertion. AB - I report two experiments studying the relationship among explicit judgments about what people see, know, and should assert. When an object of interest was surrounded by visibly similar items, it diminished people's willingness to judge that an agent sees, knows, and should tell others that it is present. This supports the claim, made by many philosophers, that inhabiting a misleading environment intuitively decreases our willingness to attribute perception and knowledge. However, contrary to stronger claims made by some philosophers, inhabiting a misleading environment does not lead to the opposite pattern whereby people deny perception and knowledge. Causal modeling suggests a specific psychological model of how explicit judgments about perception, knowledge, and assertability are made: knowledge attributions cause perception attributions, which in turn cause assertability attributions. These findings advance understanding of how these three important judgments are made, provide new evidence that knowledge is the norm of assertion, and highlight some important subtleties in folk epistemology. PMID- 26851404 TI - Examination of the pathogenic potential of Candida albicans filamentous cells in an animal model of haematogenously disseminated candidiasis. AB - The opportunistic fungal pathogen Candida albicans is an increasingly common threat to human health. Candida albicans grows in several morphologies and mutant strains locked in yeast or filamentous forms have attenuated virulence in the murine model of disseminated candidiasis. Thus, the ability to change shape is important for virulence. The transcriptional repressors Nrg1p and Tup1p are required for normal regulation of C. albicans morphology. Strains lacking either NRG1 or TUP1 are constitutively pseudohyphal under yeast growth conditions, and display attenuated virulence in the disseminated model. To dissect the relative importance of hyphae and pseudohyphae during an infection, we used strains in which the morphological transition could be externally manipulated through controlled expression of NRG1 or TUP1. Remarkably, hyphal form inocula retain the capacity to cause disease. Whilst induction of a pseudohyphal morphology through depletion of TUP1 did result in attenuated virulence, this was not due to a defect in the ability to escape the bloodstream. Instead, we observed that pseudohyphal cells are cleared from tissues much more efficiently than either hyphal (virulent) or yeast form (avirulent) cells, indicating that different C. albicans morphologies have distinct interactions with host cells during an infection. PMID- 26851406 TI - Patient-reported outcomes in head and neck and thyroid cancer randomised controlled trials: A systematic review of completeness of reporting and impact on interpretation. AB - AIM: To determine the completeness of reporting of patient-reported outcomes (PROs) of head and neck cancer (HNC) and thyroid cancer randomised-controlled trials (RCTs) and identify PRO measures used. METHODS: A systematic literature search was conducted for HNC and thyroid cancer RCTs with PRO end-points (January 2004-June 2015). Two investigators independently extracted data, assessed adherence to the International Society for Quality of Life Research (ISOQOL) PRO reporting standards and concordance between hypotheses and PRO measures used. Data were entered into the Patient-Reported Outcomes Measurements Over Time in Oncology (PROMOTION) Registry. RESULTS: Sixty-six RCTs were included, 56 (85%) HNC and 10 (15%) thyroid cancer. Twenty-two (33%) included a primary and 44 (67%) included a secondary PRO end-point. A total of 40 unique PRO measures were used. Adherence to the ISOQOL PRO reporting standards was higher for RCTs with primary PRO end-points than for secondary PRO end-points: (mean adherence of 43% and 29% respectively). Completeness of PRO reporting did not improve with time: r = .13, p = .31. ISOQOL checklist items poorly reported included: PRO hypothesis (reported for eight RCTs, 12%), justification chosen of PRO measures (n = 16, 24%), rates of missing PRO data (n = 19, 29%), and generalisability of results (n = 12, 18%). Encouragingly, PROs were identified in 55 RCT abstracts (83%) and PRO results interpreted for 30 RCTs (45%). CONCLUSIONS: Reporting of PRO end-points was more comprehensive in RCTs with primary rather than secondary PRO end-points. Improvement is needed in the transparent reporting of PRO studies, particularly regarding data collection, analyses and generalisability of PRO results. PMID- 26851407 TI - The impact of a conditional cash transfer program on the utilization of non targeted services: Evidence from Afghanistan. AB - While existing research suggests that health-related conditional cash transfer (CCT) programs have positive impacts on the utilization of CCT-targeted health services, little is known as to whether they also influence the utilization of non-targeted health services-defined as general health services for which program participants are not financially motivated. Based on a sample of 6649 households in a CCT program that took place in May 2009-June 2011 in Afghanistan, we evaluate the impact of the receipt of CCTs on the utilization of non-targeted health services both by women, who were direct beneficiaries of the program, and by members of their households. We estimate the outcomes of interest through four probit models, accounting for potential endogeneity of the CCT receipt and dealing with lack of credible exclusion restrictions in different ways. In comparison with the control group, the receipt of CCTs is found to be associated with an increase in the probability of utilizing non-targeted services among household members across regression models. The results are mixed, with regard to the utilization by women, suggesting that there exist non-economic barriers to health care, unique to women, that are not captured by the data. The results confirm the importance of accounting for direct as well as indirect effects in policy evaluation and suggest that future studies investigate more deeply the role of community health workers in removing non-economic barriers for Afghan women and the possibility of introducing an incentive structure to motivate them to contribute more actively to population health in Afghanistan. PMID- 26851408 TI - Longitudinal association between time-varying social isolation and psychological distress after the Great East Japan Earthquake. AB - BACKGROUND: The association between social isolation and psychological distress among disaster survivors is inconclusive. In addition, because these previous studies were cross-sectional in design, the longitudinal association between time varying social isolation and psychological distress was not clear. The present study examined the longitudinal association between social isolation and psychological distress after the Great East Japan Earthquake. METHODS: We analyzed longitudinal data for 959 adults who had responded to the self-report questionnaires about Lubben Social Network Scale-6 (LSNS-6) and K6 in both a community-based baseline survey (2011) and a follow-up survey (2014) after the disaster. Participants were categorized into four groups according to changes in the presence of social isolation (<12/30 of LSNS-6) at two time points (2011 and 2014): "remained socially isolated", "became not socially isolated", "remained not socially isolated", and "became socially isolated". We defined a K6 score of >= 10/24 as indicating the presence of psychological distress. We used multiple logistic regression analysis to estimate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) to indicate how the change in social isolation was related to changes in psychological distress over 3 years. RESULTS: Among the participants who had not shown psychological distress at the baseline, the rates of deterioration of psychological distress were significantly lower in participants who "became not socially isolated" (multivariate OR = 0.26, 95% CI = 0.08-0.70) and "remained not socially isolated" (multivariate OR = 0.49, 95% CI = 0.27-0.91), compared with participants who "remained socially isolated". Among the participants who had psychological distress at the baseline, the rate of improvement of psychological distress was significantly higher in participants who "remained not socially isolated" (multivariate OR = 2.61, 95% CI = 1.08 6.44). CONCLUSION: The present findings suggest that prevention of social isolation may be an effective public health strategy for preventing psychological distress after a natural disaster. PMID- 26851409 TI - Obstacles to "race equality" in the English National Health Service: Insights from the healthcare commissioning arena. AB - Inequitable healthcare access, experiences and outcomes across ethnic groups are of concern across many countries. Progress on this agenda appears limited in England given the apparently strong legal and policy framework. This disjuncture raises questions about how central government policy is translated into local services. Healthcare commissioning organisations are a potentially powerful influence on services, but have rarely been examined from an equity perspective. We undertook a mixed method exploration of English Primary Care Trust (PCT) commissioning in 2010-12, to identify barriers and enablers to commissioning that addresses ethnic healthcare inequities, employing:- in-depth interviews with 19 national Key Informants; documentation of 10 good practice examples; detailed case studies of three PCTs (70+ interviews; extensive observational work and documentary analysis); three national stakeholder workshops. We found limited and patchy attention to ethnic diversity and inequity within English healthcare commissioning. Marginalization of this agenda, along with ambivalence, a lack of clarity and limited confidence, perpetuated a reinforcing inter-play between individual managers, their organisational setting and the wider policy context. Despite the apparent contrary indications, ethnic equity was a peripheral concern within national healthcare policy; poorly aligned with other more dominant agendas. Locally, consideration of ethnicity was often treated as a matter of legal compliance rather than integral to understanding and meeting healthcare needs. Many managers and teams did not consider tackling ethnic healthcare inequities to be part-and-parcel of their job, lacked confidence and skills to do so, and questioned the legitimacy of such work. Our findings indicate the need to enhance the skills, confidence and competence of individual managers and commissioning teams and to improve organizational structures and processes that support attention to ethnic inequity. Greater political will and clearer national direction is also required to produce the system change needed to embed action on ethnic inequity within healthcare commissioning. PMID- 26851411 TI - Fracture pain-Traveling unknown pathways. AB - An increase of fracture incidence is expected for the next decades, mostly due to the undeniable increase of osteoporotic fractures, associated with the rapid population ageing. The rise in sports-related fractures affecting the young and active population also contributes to this increased fracture incidence, and further amplifies the economical burden of fractures. Fracture often results in severe pain, which is a primary symptom to be treated, not only to guarantee individual's wellbeing, but also because an efficient management of fracture pain is mandatory to ensure proper bone healing. Here, we review the available data on bone innervation and its response to fracture, and discuss putative mechanisms of fracture pain signaling. In addition, the common therapeutic approaches to treat fracture pain are discussed. Although there is still much to learn, research in fracture pain has allowed an initial insight into the mechanisms involved. During the inflammatory response to fracture, several mediators are released and will putatively activate and sensitize primary sensory neurons, in parallel, intense nerve sprouting that occurs in the fracture callus area is also suggested to be involved in pain signaling. The establishment of hyperalgesia and allodynia after fracture indicates the development of peripheral and central sensitization, still, the underlying mechanisms are largely unknown. A major concern during the treatment of fracture pain needs to be the preservation of proper bone healing. However, the most common therapeutic agents, NSAIDS and opiates, can cause significant side effects that include fracture repair impairment. The understanding of the mechanisms of fracture pain signaling will allow the development of mechanisms-based therapies to effectively and safely manage fracture pain. PMID- 26851410 TI - Relative deprivation and risk factors for obesity in Canadian adolescents. AB - Research on socioeconomic differences in overweight and obesity and on the ecological association between income inequality and obesity prevalence suggests that relative deprivation may contribute to lifestyle risk factors for obesity independently of absolute affluence. We tested this hypothesis using data on 25,980 adolescents (11-15 years) in the 2010 Canadian Health Behaviour in School aged Children (HBSC) study. The Yitzhaki index of relative deprivation was applied to the HBSC Family Affluence Scale, an index of common material assets, with more affluent schoolmates representing the comparative reference group. Regression analysis tested the associations between relative deprivation and four obesity risk factors (skipping breakfasts, physical activity, and healthful and unhealthful food choices) plus dietary restraint. Relative deprivation uniquely related to skipping breakfasts, less physical activity, fewer healthful food choices (e.g., fruits, vegetables, whole grain breads), and a lower likelihood of dieting to lose weight. Consistent with Runciman's (1966) theory of relative deprivation and with psychosocial interpretations of the health consequences of income inequality, the results indicate that having mostly better off schoolmates can contribute to poorer health behaviours independently of school-level affluence and subjective social status. We discuss the implications of these findings for understanding the social origins of obesity and targeting health interventions. PMID- 26851413 TI - Hand-Assisted Laparoscopic Hysterectomy for Large Uteri. PMID- 26851412 TI - Early injury to cortical and cancellous bone from induction chemotherapy for adolescents and young adults treated for acute lymphoblastic leukemia. AB - Diminished bone density and skeletal fractures are common morbidities during and following therapy for acute lymphoblastic leukemia (ALL). While cumulative doses of osteotoxic chemotherapy for ALL have been reported to adversely impact bone density, the timing of onset of this effect as well as other changes to bone structure is not well characterized. We therefore conducted a prospective cohort study in pre-adolescent and adolescent patients (10-21years) newly diagnosed with ALL (n=38) to explore leukemia-related changes to bone at diagnosis and the subsequent impact of the first phase of chemotherapy ("Induction"). Using quantitative computerized tomography (QCT), we found that pre-chemotherapy bone properties were similar to age- and sex-matched controls. Subsequently over the one month Induction period, however, cancellous volumetric bone mineral density (vBMD) decreased markedly (-26.8%, p<0.001) with sparing of cortical vBMD (tibia 0.0%, p=0.860, femur -0.7%, p=0.290). The tibia underwent significant cortical thinning (average cortical thickness-1.2%, p<0.001; cortical area-0.4%, p=0.014), while the femur was less affected. Areal BMD (aBMD) concurrently measured by dual energy X-ray absorptiometry (DXA) underestimated changes from baseline as compared to vBMD. Biochemical evidence revealed prevalent Vitamin D insufficiency and a net resorptive state at start and end of Induction. Our findings demonstrate for the first time that significant alterations to cancellous and cortical bone develop during the first month of treatment, far earlier during ALL therapy than previously considered. Given that osteotoxic chemotherapy is integral to curative regimens for ALL, these results provide reason to re evaluate traditional approaches toward chemotherapy-associated bone toxicity and highlight the urgent need for investigation into interventions to mitigate this common adverse effect. PMID- 26851414 TI - The Role of Endometrial Biopsy in the Preoperative Detection of Uterine Leiomyosarcoma. AB - STUDY OBJECTIVE: To assess the sensitivity of preoperative endometrial biopsy in detection of uterine leiomyosarcoma (ULMS). STUDY DESIGN: Retrospective analysis of a prospectively collected database (Canadian Task Force III). SETTING: Two academic tertiary referral centers. PATIENTS: All cases of ULMS treated at participating institutions between January 2005 and August 2012 were identified following IRB approval. INTERVENTIONS: Abstracted data included demographics, preoperative evaluation, presenting symptom, surgical management, pathology and clinical outcomes. Chi-square tests were used for statistical analysis. MEASUREMENTS AND MAIN RESULTS: 329 cases were identified, of which 152 cases had complete pathologic data available for review. Sixty-eight (45%) of 152 patients had endometrial sampling prior to surgery. Patients with postmenopausal bleeding were significantly more likely to be biopsied preoperatively (51.6% vs 9.5%, p = <.0001). Of those sampled, 43 (63%) underwent endometrial pipelle biopsies and 25 (37%) had dilation and curettage. Endometrial sampling was significantly more likely to detect a concern for malignancy in patients who presented with postmenopausal bleeding (72.7% vs 32.3%, p = 0.002), however it was less likely to detect malignancy in patients with abnormal premenopausal bleeding (31.8% vs 64.3%, p = .02), compared to other presenting symptoms. Overall, 51.5% of patients with ULMS on final pathology had preoperative endometrial biopsies in which leiomyosarcoma or atypical spindle cell proliferation were diagnosed, whereas 35.5% of the pre-operative biopsies identified ULMS specifically. CONCLUSIONS: The sensitivity of an endometrial biopsy to detect ULMS is low, illustrating the difficulty of diagnosing ULMS preoperatively. As expected, the probability that an endometrial biopsy will detect ULMS or a related worrisome pathological finding is higher for patients with post-menopausal bleeding. Thus, benign endometrial biopsy results, particularly in pre-menopausal patients, should be interpreted with caution if there is suspicion for leiomyosarcoma. However, a positive or suspicious result can play an important role in the subsequent management of patients with ULMS, even if the absolute numbers of affected patients are small. PMID- 26851415 TI - Elevated Serum CD95/FAS and HIF-1alpha Levels, but Not Tie-2 Levels, May Be Biomarkers in Patients With Severe Endometriosis: A Preliminary Report. AB - STUDY OBJECTIVE: To evaluate serum values of cluster of differentiation 95 (CD95/FAS), hypoxia-inducible factor 1-alpha (HIF-1alpha), and tyrosine kinase receptor 2 (Tie-2) as possible biomarkers of disease presence and severity in women with endometriosis, and to characterize the changes in these values in women with stage I/II and stage III/IV endometriosis. DESIGN: Prospective study (Canadian Task Force classification I). SETTING: University hospital. PATIENTS: Thirty women with endometriosis and 30 healthy women without endometriosis. INTERVENTION: For the diagnosis of endometriosis and prediction of its severity, we measured the serum levels of CD95/FAS, which assess apoptotic conditions, and of HIF-1alpha and Tie-2, which assess angiogenesis. Endometriosis was diagnosed and staged through surgical laparoscopy and later confirmed histologically. During the surgery, the patients with endometriosis were divided into 2 groups based on disease stage. Eleven patients had stage I/II endometriosis, and 19 had stage III/IV endometriosis. MEASUREMENTS AND MAIN RESULTS: Endometriosis was associated with increased serum CD95/FAS and HIF-1alpha levels, but not Tie-2 levels. We also determined that stage III/IV endometriosis was associated with higher serum CD95/FAS and HIF-1alpha levels, but not Tie-2 levels, compared with stage I/II endometriosis. CONCLUSION: Endometriosis, in accordance with its severity, increases serum CD95/FAS and HIF-1alpha levels, but not Tie-2 levels. These biomarkers may be useful for reproductive surgeons to improve the quality of counseling women about the presence and severity of endometriosis. PMID- 26851416 TI - Hand-Assisted Laparoscopic Hysterectomy for Large Uteri. PMID- 26851417 TI - Overview of Risk-Estimation Tools for Primary Prevention of Cardiovascular Diseases in European Populations. AB - To identify persons with a high risk for cardiovascular diseases (CVD) special tools (scores, charts, graphics or computer programs) for CVD-risk assessment based on levels of the certain risk factors have been constructed. The applicability of these instruments depends on the derivation cohorts, considered risk factors and endpoints, applied statistical methods as well as used formats. The review addresses the risk-estimation tools for primary prevention of CVD potentially relevant for European populations. The risk-estimation tools were identified using two previously published systematic reviews as well as conducting a literature search in MEDLINE and a manual search. Only instruments were considered which were derived from cohorts of at least 1,000 participants of one gender without pre-existing CVD, enable risk assessment for a period of at least 5 years, were designed for an age-range of at least 25 years and published after the year 2000. A number of risk-estimation tools for CVD derived from single European, several European and from non-European cohorts were identified. From a clinical perspective, seem to be preferable instruments for risk of CVD contemporary developed for the population of interest, which use easily accessible measures and show a high discriminating ability. Instruments, restricting risk-estimation to certain cardiovascular events, recalibrated high accuracy tools or tools derived from European populations with similar risk factors distribution and CVD-incidence are the second choice. In younger people, calculating the relative risk or cardiovascular age equivalence measures may be of more benefit. PMID- 26851418 TI - Pilot Cross-Sectional Study of Three Zoonoses (Lyme Disease, Tularaemia, Leptospirosis) among Healthy Blood Donors in Eastern Slovakia. AB - OBJECTIVE: The aim of the study was to determine the seroprevalence of three zoonotic infections among healthy blood donors/volunteers in Eastern Slovakia. METHODS: Sera from 124 blood donors were investigated for the presence of antibodies against Borrelia burgdorferi, Francisella tularensis and Leptospira pomona. The participants also completed the questionnaire about demographic, exposure and epidemiological characteristics. Two serological methods were used for the diagnosis: the enzyme linked protein A/G assay (ELPAGA) and the Western blot (WB). First, sera were screened by ELPAGA (except for leptospirosis). RESULTS: The observed seroprevalence was 15% for Lyme borreliosis (LB) and 4% for tularaemia (TUL). The results were confirmed by WB. Positive IgG antibodies (WB method) were detected only in 1.6% of examined for LB and 0.8% for TUL. Our results did not identify any antibodies against Leptospira pomona agent in the examined healthy blood donors group. CONCLUSIONS: ELPAGA seroprevalence for TUL was significantly higher in blood donors working in the agricultural area in the direct contact with hay, straw, manure, and agricultural land. Our outputs determine tick bite as a significant risk factor for LB. The study confirms the explosion of tick-borne diseases in the healthy population of people. The exposure risk for leptospirosis seems to be minimal. PMID- 26851419 TI - The Pattern of Antibiotic Prescribing by Dental Practitioners in Zagreb, Croatia. AB - BACKGROUND: Bacterial resistance is considered a consequence of misuse or overuse of antibiotics. Dentistry significantly contributes to this increasing public health problem. The aim of this cross-sectional study was to examine the pattern of antibiotics prescribed by Croatian dentists in Zagreb area. METHODS: Out of 220 Doctors of Dental Medicine (DMDs) from Zagreb 110 responded to survey. Prior to the research an ethical approval was obtained. Participants were directly contacted. The questionnaire consisted of two parts: general data on DMDs and the part concerning indications, duration, type and dosage of antibiotic therapy. Data were processed using MS Excel and SPSS for Windows, Version 17.0. Statistical significance was tested by Fisher's exact test, chi-square test, Mann Whitney U test and Spearman's rank correlation at the level of statistical significance p<0.05. RESULTS: During the period of two months, the doctors prescribed antibiotics to 1,500 patients, 690 (46%) were men and 810 (54%) women. The most often prescribed antibiotics were penicillin (72.5% of patients), represented mostly by amoxicillin in combination with clavulanic acid (57.6%). The most common indication for the prescribed antibiotics was periapical or periodontal abscess (44%). Definite clinical indication (71.2%) was stated as the most common reason for antibiotic prescription. Antibiotic therapy usually lasted 7 days (62.9%). The doctors prescribed daily doses of antibiotics according to the instructions for the use of specific drugs. CONCLUSION: The examined subjects prescribe antibiotics according to the curriculum taught at the School of Dental Medicine for majority of types, doses and duration of the treatments, although antibiotics over-prescription in cases without medical indication was observed. The national guidelines on antibiotic regimens are required in order to reduce unnecessary antibiotic use. PMID- 26851420 TI - Antibiotics in Serbian Households: a Source of Potential Health and Environmental Threats? AB - AIM: Worldwide data indicate that antibiotics are frequently used inappropriately. The objective of this study was to investigate the extent of storage and wastage of antibacterial agents in households in Novi Sad, Serbia. METHODS: The study was performed in 8 months period (December 2011-July 2012) in households in Novi Sad, Serbia. The households were randomly selected from the telephone directory. The interviewer performed the survey visiting each household. RESULTS: The total number of antibacterial agents in the 383 surveyed households was 318, constituting 7.3% of the total stored medications. From 383 families included in the study antibiotics were found in 178 (46.5%). In 13 (7.3%) families were found more than one pack of the same antibiotics. The median number of antibacterial agents per household was 1 (range 1-5). The most common antibacterial agents that were not in current use were cephalexin (22.1%) and amoxicillin (16.6%), followed by doxycycline (11.4%), sulfamethoxazole/trimethoprim (11.4%) and amoxicillin/clavulanic acid (9.2%). The percentage of expired antibacterial agents was 20.8%, while 85.2% were not currently in use. CONCLUSION: Antibacterial agents were commonly encountered in Serbian households, and a relatively large percentage was wasted. Informational and educational activities aimed at improving the public knowledge about antimicrobials play the leading role in reducing imprudent use of antibiotics. PMID- 26851421 TI - Cutaneous Melanoma, Hodgkin's Lymphoma and non-Hodgkin's Lymphoma: Common Risk Factors? AB - AIM: An epidemiological cross-sectional study was conducted to evaluate the association between cutaneous melanoma, Hodgkin's lymphoma and non-Hodgkin's lymphoma in 40 European countries. METHODS: Incidence rates were obtained from the database of the International Agency for Research of Cancer (IARC). We analyzed age-adjusted and gender-stratified incidence rates for cutaneous melanoma, Hodgkin's lymphoma and non-Hodgkin's lymphoma in 40 European countries. All European countries included had registration systems that fulfilled the quality criteria of IARC. Normal distribution of the variables was examined using Kolmorov-Smirnov test before calculating their correlations using Pearson's Correlation test. RESULTS: In males, positive correlations were found between cutaneous melanoma, Hodgkin's lymphoma (r=0.14, p=0.38), and non-Hodgkin's lymphoma (r=0.64, p<0.001). In females, negative correlation was found between cutaneous melanoma and Hodgkin's lymphoma (r=0.28, p=0.08), however, positive correlation was found between cutaneous melanoma and non-Hodgkin's lymphoma (r=0.72, p<0.001). CONCLUSION: Our findings raise the hypothesis about common risk factors for cutaneous melanoma and non-Hodgkin's lymphoma. New epidemiological and genetic studies are needed to identify possible common risk factors. PMID- 26851422 TI - What Is the Real Public Health Significance of Iron Deficiency and Iron Deficiency Anaemia in Croatia? A Population-Based Observational Study on Pregnant Women at Early Pregnancy from Eastern Croatia. AB - AIM: Studies imply that significance of iron deficiency (ID) and iron deficiency anaemia (IDA) for pregnancy outcomes is especially highlighted in the early pregnancy. Prevalence around the world varies widely, however, no data is available up to date for Croatia or neighbouring countries. Therefore, the objective was to determine the prevalence of ID and IDA among pregnant women from Croatia at the first trimester. Also, the aim was to compare two criterions; the World Health Organization (WHO) one and the clinical one. METHODS: Randomised observational population based study was set up and 265 pregnant women at the first trimester were enrolled. RESULTS: Based on the WHO criteria, 17.7% on haemoglobin basis and 18.5% on haematocrit basis had either ID or IDA. Clinical criteria showed that even 32.8% had either ID or IDA (transferrin saturation <20.0%). The WHO criterion shows less sensitivity, especially in detecting less severe stages of IDA. CONCLUSIONS: Regardless of the criteria used, ID and IDA present a mild to moderate public health problem in pregnant women population. This high share of pregnant women who are starting their pregnancy as iron deficient, presents a potentially high risk for the pregnancy outcomes, especially in terms of a newborn, and it is fully justified to treat them as diseases of public health significance. PMID- 26851423 TI - Birth Outcomes of Children Born to Women with Rheumatoid Arthritis. AB - AIM: The aim of the study was to estimate the possible risk of adverse birth outcomes of children born to mothers with rheumatoid arthritis (RA). METHODS: The dataset of large population-based Hungarian Case-Control Surveillance System of Congenital Abnormalities from 1980-1996 was evaluated including 22,843 cases with congenital abnormalities and 38,151 matched controls without any defect. RESULTS: 36 cases (0.16%) had mothers with RA, while 68 controls (0.18%) were born to mothers without RA (OR=0.9, 95% CI=0.3-1.6). A higher risk for congenital abnormalities in the offspring of pregnant women with RA was not found. In fact there was a larger mean birth weight in the newborns without any defect of mothers with RA and it was associated with a somewhat lower rate of low birth weight. CONCLUSIONS: RA seems to have a beneficial effect not only for pregnant women but for their foetuses as well. PMID- 26851424 TI - Time-Site Survey of Substance Use, Sexual Behaviours, and HIV-Testing Practices among Women Attending Social Venues in Prague. AB - AIM: The rates of HIV acquired through heterosexual contact are increasing in the Czech Republic. This study explored potential HIV risk associa-tions with alcohol, illicit drugs and sexual behaviours among adults from a community-based sample attending gay- and non-gay venues in Prague. METHODS: Women attending bars, cafes and beer gardens in central Prague responded to the self administered, time-site survey. Alcohol use was measured by the AUDIT-C and CAGE questionnaires. Sexual network structuring identified number, gender and coital frequency with current and recent sexual partners. Statistical analysis included central tendency, chi-square and logistic regression. Female participants (n=124) ranged from 18 to 67 years of age (mean 29 years); 25% self-identified as non heterosexual. RESULTS: We found alcohol to be the preferred drug of choice. Younger heterosexual women with new and casual sexual partners were more likely to use alcohol excessively. Women with children reported the least alcohol use. Sixty percent of the sample had never used condoms; condom-use was associated with longer relationship duration and discussions about HIV status with a sexual partner; non-use tended to occur among unmarried women with multiple male partners in short, serial sexual relationships. Women who sought HIV testing tended to be younger and more self-identified as non-heterosexual. Protective practices were rarely reported even when HIV transmission increases via heterosexual sexual partnering. CONCLUSION: Further research is recommended regarding cultural and contextual influences on HIV risk behaviours among Czech women. PMID- 26851425 TI - Severity, Causes and Outcomes of Traumatic Brain Injuries Occurring at Different Locations: Implications for Prevention and Public Health. AB - AIM: Traumatic brain injuries (TBI) are a major public health problem. Although they are well studied, information on some aspects, such as the place of occurrence, is limited. The aim of this study was to describe the patterns of severity, causes and outcomes of TBI occurring at different locations and to identify the primary populations at risk of suffering TBI at each of the analysed locations. METHODS: 1,818 patients with TBI admitted to hospitals in Austria, Slovakia, Croatia, Bosnia, and Macedonia were analysed. Primary populations at risk, injury severity and extent along with short/long-term outcomes were analysed for TBI at each location. RESULTS: The highest mean age (57.9 years, p<0.001) was observed in injuries at home. The distribution of injury causes across the group was significantly different (p<0.001), with falls (39%) and traffic accidents (30%) being predominant. TBI occurring on roads or highways were the most severe (mean ISS=32.5, p<0.001; mean GCS=7.8, p<0.001). Injuries at home had the worst outcome (50% mortality, p<0.001 and 70% unfavourable outcome, p<0.001) whereas TBI at sport facilities or outdoors had the best outcome (24% mortality, 44% unfavourable outcome). When adjusted for age and severity, TBI occurring at home had the highest odds of mortality (OR=3.12, 95% CI=1.86-5.25) and unfavourable outcome (OR=2.51, 95% CI=1.54-4.08), compared to sports facility and outdoors as a reference. CONCLUSIONS: TBI at different locations display distinctive patterns as to causes, severity, outcome and populations at risk. Location is therefore a relevant epidemiological aspect of TBI and we advocate its inclusion in future studies. Definitions of primary populations at risk at different locations could help in targeted public health actions. PMID- 26851426 TI - Complementary Feeding Practices of Children Aged 12-23 Months in Turkey. AB - AIM: This study was conducted to determine the breastfeeding and complementary feeding attitudes and practices of women with children aged 12-23 months in three different regions in Turkey. METHODS: From 12 geographical regions (Nomenclature of Territorial Units for Statistics - NUTS 1), 3 regions were selected depending on the Turkish Demographic Health Survey 2003 (TDHS) results of nutritional status of children. Then, a weighted, multistage, stratified cluster sampling was used. In total, 1,486 children aged 12-23 months and mother pairs were enrolled. Mothers were face-to-face interviewed with trained health workers to collect information on breastfeeding practices, amount and types of complementary foods introduced and potentially related factors and demographic data filled in a questionnaire. RESULTS: The percentage of ever breastfeeding was 98.7%, no differences were determined among regions for ever breastfeeding (p>0.05). Duration of exclusive breastfeeding was 5.1+/-2.4 months. The shortest duration of exclusive breastfeeding was found in the good nutritional status region as 4.8+/-2.4 months (p<0.05). Yogurt, bread, pasta, fruits and vegetables were the foods introduced to the majority of the children. Red meat, poultry and fish were introduced to children in later ages in the low nutritional status region compared to middle and good nutritional status regions. Complementary feeding is introduced earlier than 6 months of age. CONCLUSIONS: Raising awareness on appropriate infant and young child feeding practices should be a priority. Enhancing of mothers knowledge, attitudes and practices on breastfeeding and complementary feeding is needed. PMID- 26851427 TI - Testing Two Nutrient Profiling Models of Labelled Foods and Beverages Marketed in Turkey. AB - AIM: The objective of this study was to evaluate the nutrient profile of labelled foods and also understand the application of two international nutrient profiling models of labelled foods and beverages. METHODS: WXYfm and NRF 9.3 nutrient profiling models were used to evaluate 3,171 labelled foods and beverages of 38 food categories and 500 different brands. RESULTS: According to the WXYfm model, pasta, grains and legumes and frozen foods had the best scores whereas oils had the worst scores. According to the NRF 9.3 model per 100 kcal, the best scores were obtained for frozen foods, grains and legumes and milk products whereas the confectionery foods had the worst scores. According to NRF 9.3 per serving size, grains and legumes had the best scores and flavoured milks had the worst scores. A comparison of WXYfm and NRF 9.3 nutrient profiling models ranked scores showed a high positive correlation (p=0.01). CONCLUSIONS: The two nutrient models evaluated yielded similar results. Further studies are needed to test other category specific nutrient profiling models in order to understand how different models behave. PMID- 26851428 TI - Assessment of Potential Health Hazards During Emission of Hydrogen Sulphide from the Mine Exploiting Copper Ore Deposit - Case Study. AB - AIM: The aim of this study was to determine hydrogen sulphide concentration emitted from the mine extracting copper ore, to evaluate potential adverse health effects to the population living in four selected villages surrounding the exhaust shaft. MATERIALS: Maximum measured concentration of hydrogen sulphide in the emitter is 286 ug/m3. Maximum emission calculated from the results of determinations of concentrations in the emitter is 0.44 kg/h. RESULTS: In selected villages hydrogen sulphide at concentrations exceeding 4 ug/m3 was not detected in any of the 5-hour air samples. In all locations, the estimated maximum 1-hour concentrations of hydrogen sulphide were below 1 ug/m3, and the estimated mean annual concentrations were below 0.53 ug/m3. CONCLUSION: Any risk to the health of people in the selected area is not expected. As indicated by the available data on the threshold odour, the estimated concentrations of hydrogen sulphide may be sensed by humans. PMID- 26851429 TI - Depression and Self-Esteem in Early Adolescence. AB - AIM: Depression prevalence has increased in the last few decades, affecting younger age groups. The aim of this research was to determine the range of depression and low self-esteem in elementary school children in the city of Split. Testing was carried out at school and the sample comprised 1,549 children (714 boys and 832 girls, aged 13). METHODS: Two psychological instruments were used: the Coopersmith Self-Esteem Inventory (SEI) and the Children and Adolescent Depression Scale (SDD). RESULTS: The average value of scores obtained by SEI test was 17.8 for all tested children. No statistically significant difference was found be-tween boys and girls. It was found that 11.9% of children showed signs of clinically significant depression, and 16.2% showed signs of depression. Statistically significant association between low self-esteem and clinically significant depression was found. No statistically significant difference among boys and girls according to dimension of cognitive depression was found, whereas statistically significant level of emotional depression was higher in girls than boys. It was found that both dimensions of depression decreased proportionally with the increase of SEI test score values: cognitive and emotional dimension of depression. CONCLUSION: The results of this study show that it is necessary to provide early detection of emotional difficulties in order to prevent serious mental disorders. PMID- 26851430 TI - Evaluation of Cat Scratch Disease Cases Reported from Turkey between 1996 and 2013 and Review of the Literature. AB - BACKGROUND: Cat scratch disease (CSD), the most common cause of chronic lymphadenopathy among children and adolescents, typically features regional lymphadenitis associated with inoculation site due to a cat scratch or bite. OBJECTIVE: The aim of this study was to systematically review the articles related to CSD which were reported from Turkey in national and international journals in the last 18 years with a pooled-analysis method. METHODS: The articles related to CSD were retrieved by search of four national (Ulakbim Turkish Medical Literature Databases) and three international databases (Pub-Med, Science Citation Index (SCI) and Google scholar). RESULTS: Between the years 1996 2013, CSD cases have been published in a total of 16 articles (4 international, 12 national). These articles which were presented as a case report included a total of 18 CSD cases (38.8% women, 61.2% men; median age 16 years). The most common clinicopathologic subtypes of CSD are regional lymphadenitis (n=9), hepatosplenic (n=3) and neuroretinitis (n=2). The most common complaints of patients were swelling (94.4%), fever (61.2%) and weakness (50%) at admission. On exam, the most common signs were lymphadenopathy (94.4%), fever (61.2%), splenomegaly (16.6%), and skin eruption (16.6%). CONCLUSION: This pooled analysis which enabled the evaluation of a large number of CSD cases, indicated that careful evaluation of clinical findings and histopathological investigation will provide valuable support for diagnosis and treatment of CSD. PMID- 26851431 TI - Remedy for Work Stress: the Impact and Mechanism of Ethical Leadership. AB - AIM: Ethical leadership was characterized by integrity, honesty and trustworthiness. The purpose of this study was to investigate whether and how ethical leadership relates to employees' work stress, specifically the mediating role of leader-member exchange (LMX), which referred to the dyadic exchange relationships between supervisors and subordinates within the workplace. METHODS: Cross-sectional data for ethical leadership, LMX, perception of work stress, and control variables were collected through the questionnaire that included 47 multiple-choice questions and 3 open-ended questions. Double-blind design was adopted in this study. Hypotheses were tested by hierarchical regression analysis. RESULTS: 203 first-line technical support employees from a communications enterprise participated in this study (return ratio 98.5%). Of the respondents, 58.6% were male, average age was 35.24 years, average years in the company and in current position were 13.67 years and 11.12 years, respectively. Results revealed that the subjective evaluation of supervisors' ethical leadership was negatively related to employees' perception of work stress (beta= 0.24, p<0.001), and this relationship was completely mediated by LMX. CONCLUSIONS: Through establishing high-quality LMX, ethical leadership played an important role in relieving employees' perception of work stress. PMID- 26851432 TI - Neonatal Mortality and Morbidity in Regional Provincial Hospitals in the People's Democratic Republic of Laos. AB - OBJECTIVE: The aim of this study was to identify the causes and incidences of neonatal diseases and deaths in five provincial hospitals in People's Democratic Republic of Laos retrospectively for the years 2010-12. METHODS: Data of neonatal patients were collected before a 3-year-training program for medical and nursing staff involved in the care of newborn infants in the provincial and associated district hospitals. RESULTS: In the years 2010-12, a total of 1673 neonatal patients were treated in the provincial hospitals. The reasons of treatment were as follows: 48% infections, 17% complications of prematurity, 14% intrapartum related complications and 9% other, not categorized diseases. The average mortality rate in all hospitals was 6.5%. The main causes of death were complications because of prematurity, infectious diseases and asphyxia. CONCLUSION: These data could be the basis for any teaching program aimed at reducing neonatal mortality. Furthermore, they enable an evaluation of the ongoing teaching program. PMID- 26851433 TI - Scrub Typhus: A Clinico-Laboratory Differentiation of Children with and without Meningitis. AB - Neurological involvement in the form of meningitis or meningoencephalitis, although well documented in scrub typhus, has not been extensively studied in the pediatric population. We report the clinical and laboratory profile of 96 children with scrub typhus and compared those with and without meningitis. Twenty seven (28%) children had clinical and laboratory evidence of meningitis. The most frequent presenting features were fever (100%), meningeal signs (66.6%), nausea and vomiting (56.3%), seizures (55.5%) and altered sensorium (51.8%). The children with meningitis presented early and had significantly lower respiratory and renal impairments when compared with the non-meningitis group. Cerebrospinal fluid (CSF) analysis revealed elevated total leukocyte count (86.73 +/- 94.50 cells/mm(3)), mononuclear pleocytosis (lymphocyte percentage of 76.85 +/- 15.86), elevated proteins (108.33 +/- 52.63 mg%) and normal CSF glucose (64.18 +/- 15.92 mg%). We conclude that meningitis is a common and early complication of childhood scrub typhus. The CSF reveals a lymphocytic pleocytosis, raised proteins and a normal glucose level. These children respond promptly to appropriate antibiotics as do children without meningitis. PMID- 26851434 TI - Outcome of Severe Dengue Viral Infection-caused Acute Liver Failure in Thai Children. AB - To determine clinical course and outcomes of liver functions in children with dengue viral infection-caused acute liver failure (ALF), the records of patients aged <15 years attending our institution during 1989-2011 were reviewed. Of the 41 ALF patients, 2, 6 and 33 patients had dengue hemorrhagic fever grade II, III and IV, respectively. Multiorgan failure including respiratory failure, massive bleeding and acute kidney injury occurred in 80.0%, 96.0% and 84.0% of the ALF cases, respectively, with an overall fatality rate of 68.3%. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were highest on the day that the patient developed ALF. Lactate dehydrogenase levels had positive correlations with AST (r = 0.95) and ALT (r = 0.87) (all p < 0.01). The median (interquartile range) days before the AST and ALT levels returned to lower than 200 U/L after the ALF were 10.5 (8.8, 12.8) and 10.5 (7.8, 14.0) days, respectively. PMID- 26851435 TI - Clinical Manifestations of Hyponatremia and Hypernatremia in Under-Five Diarrheal Children in a Diarrhea Hospital. AB - OBJECTIVE: To study clinical manifestations and outcome of hyponatremia and hypernatremia in children with diarrhea. METHOD: We compared children aged 0-59 months hospitalized from 1 January to 31 December 2013 with hyponatremia (serum sodium <130 mmol/l), hypernatremia (serum sodium >150 mmol/l) and normonatremia (serum sodium 135-145 mmol/l). RESULTS: The case fatality was significantly higher among the children with hypernatremia and hyponatremia than normonatremia. A logistic regression analysis adjusting for potential confounders revealed that children with hyponatremia are more likely to have convulsions, have severe acute malnutrition and be of older age compared with children with normal serum sodium. Children with hypernatremia are more likely to have convulsions and dehydration than normonatremic children (for all p < 0.05). CONCLUSION: Early diagnosis and prompt management of hypo- and hypernatremia by identifying simple clinical predicting factors of these two conditions in diarrheal children <5 years of age is critically important to prevent deaths in such children, especially in resource-limited settings. PMID- 26851436 TI - Impacted Sharp Oesophageal Foreign Bodies--A Novel Technique of Removal with the Paediatric Bronchoscope. AB - Sharp foreign bodies in the oesophagus may present as an entirely asymptomatic child with only radiological evidence but require emergent surgical management. Safety pins, razor blades and needles are a few of the commonly ingested sharp objects in developing countries. The open safety pin is a particularly interesting clinical problem, as the management depends on its location and orientation. Many methods and instruments have been used over the years to remove them from the upper digestive tract. We present a novel method using the rigid paediatric bronchoscope and alligator forceps for the extraction of this unusual foreign body from the oesophagus of a 6 year old girl. PMID- 26851437 TI - Selection and constraints on offspring size-number trade-offs in sand lizards (Lacerta agilis). AB - The trade-off between offspring size and number is a central component of life history theory, postulating that larger investment into offspring size inevitably decreases offspring number. This trade-off is generally discussed in terms of genetic, physiological or morphological constraints; however, as among-individual differences can mask individual trade-offs, the underlying mechanisms may be difficult to reveal. In this study, we use multivariate analyses to investigate whether there is a trade-off between offspring size and number in a population of sand lizards by separating among- and within-individual patterns using a 15-year data set collected in the wild. We also explore the ecological and evolutionary causes and consequences of this trade-off by investigating how a female's resource (condition)- vs. age-related size (snout-vent length) influences her investment into offspring size vs. number (OSN), whether these traits are heritable and under selection and whether the OSN trade-off has a genetic component. We found a negative correlation between offspring size and number within individual females and physical constraints (size of body cavity) appear to limit the number of eggs that a female can produce. This suggests that the OSN trade-off occurs due to resource constraints as a female continues to grow throughout life and, thus, produces larger clutches. In contrast to the assumptions of classic OSN theory, we did not detect selection on offspring size; however, there was directional selection for larger clutch sizes. The repeatabilities of both offspring size and number were low and we did not detect any additive genetic variance in either trait. This could be due to strong selection (past or current) on these life-history traits, or to insufficient statistical power to detect significant additive genetic effects. Overall, the findings of this study are an important illustration of how analyses of within individual patterns can reveal trade-offs and their underlying causes, with potential evolutionary and ecological consequences that are otherwise hidden by among-individual variation. PMID- 26851438 TI - High total metabolic tumor volume in PET/CT predicts worse prognosis in diffuse large B cell lymphoma patients with bone marrow involvement in rituximab era. AB - Bone marrow involvement (BMI) in diffuse large B cell lymphoma (DLBCL) was naively regarded as an adverse clinical factor. However, it has been unknown which factor would separate clinical outcomes in DLBCL patients with BMI. Recently, metabolic tumor volume (MTV) on positron emission tomography/computed tomography (PET/CT) was suggested to predict prognosis in several lymphoma types. Therefore, we investigated whether MTV would separate the outcomes in DLBCL patients with BMI. MTV on PET/CT was defined as an initial tumor burden as target lesion >= standard uptake value, 2.5 in 107 patients with BMI. Intramedullary (IM) MTV was defined as extent of BMI and total MTV was as whole tumor burden. 260.5 cm(3) and 601.2 cm(3) were ideal cut-off values for dividing high and low MTV status in the IM and total lymphoma lesions in Receiver Operating Curve analysis. High risk NCCN-IPI (p<0.001, p<0.001), bulky disease (p=0.011, p=0.005), concordant subtype (p=0.025, p=0.029), high IM MTV status (p<0.001, p<0.001), high total MTV status (p<0.001, p<0.001), and >= 2CAs in BM (p=0.037, p=0.033) were significantly associated with progression-free survival (PFS) and overall survival (OS) than other groups. In multivariate analysis, high risk NCCN IPI (PFS, p=0.006; OS, p=0.013), concordant subtype (PFS, p=0.005; OS, p=0.007), and high total MTV status (PFS, p<0.001; OS, p<0.001) had independent clinical impacts. MTV had prognostic significances for survivals in DLBCL with BMI. PMID- 26851440 TI - An injectable, dual pH and oxidation-responsive supramolecular hydrogel for controlled dual drug delivery. AB - A novel pH and oxidation dual-responsive and injectable supramolecular hydrogel was developed, which was formed from multi-block copolymer poly(ether urethane) (PEU) and alpha-cyclodextrin (alpha-CD) inclusion complexes (ICs). The PEU copolymer was synthesized through a simple one-pot condensation polymerization of poly(ethylene glycol), di(1-hydroxyethylene) diselenide, dimethylolpropionic acid and 3-isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate. In aqueous solution, the amphiphilic PEU copolymers could self-assemble into nanoparticles with dual pH and oxidation sensitivities, which can efficiently load and controllably release a hydrophobic drug indomethacin (IND). Then a dual-drug loaded supramolecular hydrogel was obtained by addition of alpha-CD and hydrophilic model drug (rhodamine B, RB) into the resulting IND-loaded PEU nanoparticle solution. The rheology studies showed that the supramolecular hydrogels with good injectability underwent a pH-induced reversible sol-gel transition and an oxidation-triggered degradation behavior. The in vitro drug release results demonstrated that the hydrogels showed dual drug release behavior and the release rates could be significantly accelerated by addition of an oxidizing agent (H2O2) or increasing the environmental pH. Therefore, this injectable and dual stimuli responsive supramolecular hydrogel based codelivery systems could potentially be a promising candidate for controlled drug delivery systems. PMID- 26851439 TI - Copy number neutral loss of heterozygosity at 17p and homozygous mutations of TP53 are associated with complex chromosomal aberrations in patients newly diagnosed with myelodysplastic syndromes. AB - Complex karyotypes are seen in approximately 20% of patients with myelodysplastic syndromes (MDS) and are associated with a high risk of transformation to acute myeloid leukemia and poor outcomes in patients. Copy number neutral loss of heterozygosity (CN-LOH, i.e., both copies of a chromosomal pair or their parts originate from one parent) might contribute to increased genomic instability in the bone-marrow cells of patients with MDS. The pathological potential of CN-LOH, which arises as a clonal aberration in a proportion of somatic cells, consists of tumor suppressor gene and oncogene homozygous mutations. The aim of our study was to evaluate the frequency of CN-LOH at 17p in bone-marrow cells of newly diagnosed MDS patients with complex chromosomal aberrations and to assess its correlation with mutations in the TP53 gene (17p13.1). CN-LOH was detected in 40 chromosomal regions in 21 (29%) of 72 patients analyzed. The changes in 27 of the 40 regions identified were sporadic. The most common finding was CN-LOH of the short arm of chromosome 17, which was detected in 13 (18%) of 72 patients. A mutational analysis confirmed the homozygous mutation of TP53 in all CN-LOH 17p patients, among which two frameshift mutations are not registered in the International Agency for Research on Cancer TP53 Database. CN-LOH 17p correlated with aggressive disease (median overall survival 4 months) and was strongly associated with a complex karyotype in the cohort studied, which might cause rapid disease progression in high-risk MDS. No other CN-LOH region previously recorded in MDS or AML patients (1p, 4q, 7q, 11q, 13q, 19q, 21q) was detected in our cohort of patients with complex karyotype examined at the diagnosis of MDS. The LOH region appeared to be balanced (i.e., with no DNA copy number change) when examined with conventional and molecular cytogenetic methods. Therefore, a microarray that detects single-nucleotide polymorphisms is an ideal method with which to identify and further characterize CN-LOH. Our data should specify the prognosis and should lead to the identification of potential targets for therapeutic interventions. PMID- 26851441 TI - A focal adhesion kinase inhibitor 16-hydroxy-cleroda-3,13-dien-16,15-olide incorporated into enteric-coated nanoparticles for controlled anti-glioma drug delivery. AB - 16-Hydroxy-cleroda-3,13-dien-16,15-olide (HCD) which is extracted from a medicinal plant, Polyalthia longifolia, was shown to exhibit anticancer activity through apoptosis and FAK inhibition in our previous study. To improve its solubility and efficacy, a novel HCD delivery system using copper-substituted mesoporous silica nanoparticles (MSNs) was designed as a delivery vehicle, and the outer surfaces of MSNs were further coated with enteric polymers to prevent the drug from leaching in the stomach acid. All the data regarding synthesis and physical characterization, including Zeta potential, FT-IR spectra, N2 adsorption desorption isotherms (BET), drug loading, powder X-ray diffraction, Thermo gravimetric analysis (TGA), Transmission electron microscopy (TEM), and Scanning electron microscopy (SEM) were well characterized. The non-coated MSN-HCD exposed to acidic pH (1.2) showed a rapid degradation of the drug, whereas the enteric coated samples presented a sustained release profile in the gastrointestinal pHs. Cell cytotoxicity was further confirmed by the MTT-C6 Glioma cell line, in vitro. When compared with the control and pure HCD, the MSN-HCD revealed a potential anti-proliferation effect via the synergistic effect of the drug and the MSN vehicle. Additionally, this MSN-HCD had the effect of increasing the reactive oxygen species (ROS) levels and altered the Mitochondria membrane potential (MMP) in C6 cell line. The in vivo anti-tumor efficacy of enteric-coated MSN-HCD was evaluated by C6 Glioma bearing xenograft nude mice, and enteric-coated MSN-HCD clearly exhibited the greatest anti-glioma activity, as compared to the pure HCD and the untreated control. In terms of the effective treatment of brain glioma, this study provides conclusive evidence of the successful development of the anti cancer agent HCD conjugated with enteric-coated MSN as a delivery control mechanism with enhanced dissolution characteristics. PMID- 26851442 TI - Viral metagenomics: are we missing the giants? AB - Amoeba-infecting giant viruses are recently discovered viruses that have been isolated from diverse environments all around the world. In parallel to isolation efforts, metagenomics confirmed their worldwide distribution from a broad range of environmental and host-associated samples, including humans, depicting them as a major component of eukaryotic viruses in nature and a possible resident of the human/animal virome whose role is still unclear. Nevertheless, metagenomics data about amoeba-infecting giant viruses still remain scarce, mainly because of methodological limitations. Efforts should be pursued both at the metagenomic sample preparation level and on in silico analyses to better understand their roles in the environment and in human/animal health and disease. PMID- 26851443 TI - Hydrodynamics and convection enhanced macromolecular fluid transport in soft biological tissues: Application to solid tumor. AB - This work addresses a theoretical framework for transvascular exchange and extravascular transport of solute macromolecules through soft interstitial space inside a solid tumor. Most of the soft biological tissues show materialistic properties similar to deformable porous material. They exhibit mechanical behavior towards the fluid motion since the solid phase of the tumor tissue gets compressed by the drag force that is associated with the extracellular fluid flow. This paper presents a general view about the transvascular and interstitial transport of solute nutrients inside a tumor in the macroscopic level. Modified Starling's equation is used to describe transvascular nutrient transport. On the macroscopic level, motion of extracellular fluid within the tumor interstitium is modeled with the help of biphasic mixture theory and a spherical symmetry solution is given as a simpler case. This present model describes the average interstitial fluid pressure (IFP), extracellular fluid velocity (EFV) and flow rate of extracellular fluid, as well as the deformation of the solid phase of the tumor tissue as an immediate cause of extracellular fluid flow. When the interstitial transport is diffusion dominated, an analytical treatment of advection-diffusion-reaction equation finds the overall nutrient distribution. We propose suitable criteria for the formation of necrosis within the tumor interstitium. This study introduces some parameters that represent the nutrient supply from tumor blood vessels into the tumor extracellular space. These transport parameters compete with the reversible nutrient metabolism of the tumor cells present in the interstitium. The present study also shows that the effectiveness factor corresponding to a first order nutrient metabolism may reach beyond unity if the strength of the distributive solute source assumes positive non-zero values. PMID- 26851444 TI - Personal Identification in Forensic Science Using Uniqueness of Radiographic Image of Frontal Sinus. AB - Frontal sinus pattern matching is a useful means of forensic identification. By the use of radiographs forensic scientists have recognized that there are diverse anatomical variations in the structure of the frontal sinus. Radiographs are a diagnostic tool, widely used in dental practices, hospitals and other health disciplines. Most health institutions possess the facility to store radiographs over long periods of time. Frontal sinus pattern matching technique can be applied in cases where ante mortem frontal sinus radiographs are available and dental matching cannot be carried out. Frontal sinus pattern matching technique may also be used to corroborate identifications based on other techniques such as fingerprints, teeth, or circumstantial evidence. The present study was carried out to assess the effectiveness of using the radiographic image of the frontal sinus for personal identification in studied population group. The results concluded that the appearance of the radiographic image of the frontal sinus is unique for each individual. On this evidence it is proposed that frontal sinus pattern matching can be used for personal identification when other methods have failed. PMID- 26851445 TI - In Vitro Description of Macroscopic Changes of Dental Amalgam Discs Subject to High Temperatures to Forensic Purposes. AB - OBJECTIVE: To describe the behavior of 45 discs of dental amalgam of known dimension prepared from three commercially available brands of dental amalgam (Contour(r) Kerr(r)-USA, Admix(r) SDI(r)-Australia and Nu Alloy(r) Newstethic(r) Colombia) when subjected to the action of high temperatures (200 degrees C, 400 degrees C, 600 degrees C, 800 degrees C, 1000 degrees C). It was hoped to establish parameters that could be used for human dental identification in cases of charred, burned or incinerated human remains. MATERIALS AND METHODS: A pseudo experimental descriptive in-vitro study was designed to describe the macroscopic physical changes to the surface of 45 discs of pre-prepared amalgam of three commercially available brands exposed to a range of high temperatures. RESULTS: Characteristic and repetitive physical changes were a noticeable feature of the discs of amalgam of each brand of amalgam subjected to the different temperature ranges. These physical changes included changes in dimensional stability, changes in texture, changes in colour, changes in the appearance of fissures and cracks and changes in the fracture and fragmentation of the sample. CONCLUSIONS: The characteristics of dental amalgam may be of assistance in cases of human identification where charred, burned or incinerated human remains are a feature and where fingerprints or other soft tissue features are unavailable. PMID- 26851446 TI - Histological assessment of cellular changes in postmortem gingival specimens for estimation of time since death. AB - Estimating the time after death is an important aspect of the role of a forensic expert. After death, the body undergoes substantial changes in its chemical and physical composition which can prove useful in providing an indication of the post-mortem interval. The most accurate estimate of the time of death is best achieved early in the post-mortem interval before the many environmental variables are able to affect the result. Whilst dependence on macroscopic observations was the foundation of the past practice, the application of histological techniques is proving to be an increasingly valuable tool in forensic research. The present study was conducted to evaluate the histologic post-mortem changes that take place in human gingival tissues and to correlate these changes with the time interval after death. Thirty one samples of post mortem human gingival tissues were obtained from a pool of decedents at varied post-mortem intervals (0-8 hrs, 8-16 hrs, 16-24 hrs). Ante-mortem samples of gingival tissues for comparison were obtained from patients undergoing crown lengthening procedure. Histological changes in the epithelium (cytoplasmic and nuclear) and connective tissue were assessed. The initial epithelial changes observed were homogenization and eosinophilia while cytoplasmic vacuolation and other alterations, including shredding of the epithelium, ballooning, loss of nuclei and suprabasilar split were noticed in late post-mortem interval (16-24 hrs). Nuclear changes such as vacuolation, karyorrhexis, pyknosis and karyolysis became increasingly apparent with lengthening post-mortem intervals. Homogenizations of collagen and fibroblast vacuolation were also observed. To conclude; the initiation of decomposition at cellular level appeared within 24 hours of death and other features of decomposition were observed subsequently. Against this background, histological changes in the gingival tissues may be useful in estimating the time of death in the early post-mortem period. PMID- 26851447 TI - Thoughts on donation of a tooth to science, in the course of dental care. AB - INTRODUCTION: Research on biological samples, including dental pulp stem cells (DPSC), has expanded considerably in recent years and is now seen as a way forward toward the possibilities of new therapies, such as craniofacial bone and tooth repair. The extraction of healthy teeth and their donation for scientific research is now well accepted by both patients and researchers alike. The present situation, as described above, presents a timely opportunity to reflect on the ethical and moral obligations of all of the stakeholders involved in this methodology. METHOD: Twenty-two patients who received dental treatment between November 2013 and February 2014 in the dental department of Louis Mourier Hospital in Colombes, France, completed a questionnaire. The questionnaire was designed to gather data in respect of giving patients optimal information necessary to acquire informed consent for extraction of teeth to be used for odontological biomedical research. RESULTS: When patients agree to donate their teeth for purposes of scientific research it is vital that they are properly informed and enabled so that they are able to give consent freely. CONCLUSIONS: The risks to patients during dental extractions are minimal. However despite the growing need for a supply of extracted teeth for dental pulp stem cell research it is imperative that any ethical questions that may be raised by potential donors guarantee the security, integrity, and respect of the intentions and aspirations of the donor. To enable the acquisition of true informed consent, this article explores how the dissemination of information relating to biomedical research in the field of dental care must remain as a duty of care and professional ethics. PMID- 26851448 TI - Cardiovascular biomarkers in paired maternal and umbilical cord blood samples at term and near term delivery. AB - BACKGROUND: Cardiovascular biomarkers might help to identify fetuses or pregnancies at risk. AIM: To examine the umbilical cord neonatal and maternal levels of cardiovascular biomarkers at the time of delivery, and to correlate maternal and fetal biomarker levels to each other, to gestational age and to delivery mode. STUDY DESIGN: In a prospective, observational, cross-sectional, single-center study biomarkers were measured in paired maternal and umbilical venous cord blood samples. SUBJECTS: The sample cohort included 66 sets of fetal and maternal blood samples (11 after multiple gestation, 53 after cesarean section, 17 after exposure to labor). OUTCOME MEASURES: Midregional pro adrenomedullin (MRproADM), midregional-pro atrial natriuretic peptide (MRproANP), brain natriuretic peptide (BNP), n-terminal-pro brain natriuretic peptide (NTproBNP), copeptin, and high sensitive troponin I (hsTnI) levels were measured. RESULTS: Mean +/- SEM for biomarker levels in umbilical venous/maternal blood were: MRproADM [nmol/L] 1.02 +/- 0.04/1.24 +/- 0.08, MRproANP [pmol/L] 215.53 +/- 12.96/54.65 +/- 3.41, BNP [pg/mL] 32.02 +/- 3.37/19.76 +/- 3.29, NTproBNP [pg/mL] 1228.94 +/- 91.73/71.48 +/- 8.65, copeptin [pmol/L] 103.42 +/- 22.89/10.41 +/- 1.71, and hsTnI [pg/mL] 13.54 +/- 5.17/4.91 +/- 2.37. Fetal MRproANP, NTproBNP, and BNP were inversely correlated with gestational age. Maternal and fetal MRproANP (r=0.472, p=0.002) and copeptin (r=0.572, p<0.001) levels were correlated, whereas there was no feto-maternal correlation for the other biomarkers. Fetal copeptin was elevated after exposure to labor. CONCLUSIONS: Biomarker levels appear to be regulated independently in mother and fetus. Fetal biomarkers are influenced by gestational age and delivery mode. In this study on term and near term pregnancies without specific fetal pathology, correlation between paired maternal and fetal biomarker levels was weak or not demonstrable. PMID- 26851449 TI - Quantitative in vivo CT arthrography of the human osteoarthritic knee to estimate cartilage sulphated glycosaminoglycan content: correlation with ex-vivo reference standards. AB - OBJECTIVE: Recently, computed tomography arthrography (CTa) was introduced as quantitative imaging biomarker to estimate cartilage sulphated glycosaminoglycan (sGAG) content in human cadaveric knees. Our aim was to assess the correlation between in vivo CTa in human osteoarthritis (OA) knees and ex vivo reference standards for sGAG and collagen content. DESIGN: In this prospective observational study 11 knee OA patients underwent CTa before total knee replacement (TKR). Cartilage X-ray attenuation was determined in six cartilage regions. Femoral and tibial cartilage specimens harvested during TKR were re scanned using equilibrium partitioning of an ionic contrast agent with micro-CT (EPIC-MUCT), which served as reference standard for sGAG. Next, cartilage sGAG and collagen content were determined using dimethylmethylene blue (DMMB) and hydroxyproline assays. The correlation between CTa X-ray attenuation, EPIC-MUCT X ray attenuation, sGAG content and collagen content was assessed. RESULTS: CTa X ray attenuation correlated well with EPIC-MUCT (r = 0.76, 95% credibility interval (95%CI) 0.64 to 0.85). CTa correlated moderately with the DMMB assay (sGAG content) (r = -0.66, 95%CI -0.87 to -0.49) and to lesser extent with the hydroxyproline assay (collagen content) (r = -0.56, 95%CI -0.70 to -0.36). CONCLUSIONS: Outcomes of in vivo CTa in human OA knees correlate well with sGAG content. Outcomes of CTa also slightly correlate with cartilage collagen content. Since outcomes of CTa are mainly sGAG dependent and despite the fact that further validation using hyaline cartilage of other joints with different biochemical composition should be conducted, CTa may be suitable as quantitative imaging biomarker to estimate cartilage sGAG content in future clinical OA research. PMID- 26851450 TI - Expression of the semicarbazide-sensitive amine oxidase in articular cartilage: its role in terminal differentiation of chondrocytes in rat and human. AB - OBJECTIVE: Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the oxidation of primary amines into ammonia and reactive species (hydrogen peroxide, aldehydes). It is highly expressed in mammalian tissues, especially in vascular smooth muscle cells and adipocytes, where it plays a role in cell differentiation and glucose transport. The study aims at characterizing the expression and the activity of SSAO in rat and human articular cartilage of the knee, and to investigate its potential role in chondrocyte terminal differentiation. DESIGN: SSAO expression was examined by immunohistochemistry and western blot. Enzyme activity was measured using radiolabeled benzylamine as a substrate. Primary cell cultures of rat chondrocytes were treated for 21 days by a specific SSAO inhibitor, LJP 1586. Terminal chondrocyte differentiation markers were quantified by RT-qPCR. The basal and IL1beta-stimulated glucose transport was monitored by the entrance of (3)[H]2-deoxyglucose in chondrocytes. RESULTS: SSAO was expressed in chondrocytes of rat and human articular cartilage. SSAO expression was significantly enhanced during the hypertrophic differentiation of chondrocytes characterized by an increase in MMP13 and in alkaline phosphatase (ALP) expressions. SSAO inhibition delayed the late stage of chondrocyte differentiation without cell survival alteration and diminished the basal and IL1beta-stimulated glucose transport. Interestingly, SSAO activity was strongly increased in human osteoarthritic cartilage. CONCLUSIONS: SSAO was expressed as an active form in rat and human cartilage. The results suggest the involvement of SSAO in rat chondrocyte terminal differentiation via a modulation of the glucose transport. In man, the increased SSAO activity detected in osteoarthritic patients may trigger hypertrophy and cartilage degeneration. PMID- 26851451 TI - Development and application of novel clonazepam molecularly imprinted coatings for stir bar sorptive extraction. AB - The molecularly imprinted magnetic stir bar coatings were created based on graft functional Fe3O4 nanoparticles with magnetic field-induced self-assembly. The magnetic complex including clonazepam as template, the graft-functional Fe3O4 nanoparticles and methacrylic acid as monomers was pre-assembled through pi-pi interaction and hydrogen bonding, then was directionally adsorbed on the surface of magnetic stir bar under the magnetic induction. The molecularly imprinted coating with well-ordered structure was generated by one-step copolymerization based on the cross linking of ethylene glycol dimethacrylate. The molecularly imprinted coating with multiple recognition sites could be manufactured and applied in polar solvents, and showed superior selectivity and fast binding kinetics for benzodiazepines. The analytes in herbal health foods, treated by stir bar sorptive extraction, were determined by HPLC-UV. Good linearity was observed in the range of 0.01-2 MUg mL(-1). The content of clonazepam in the herbal health foods was found to be 44 ng g(-1), and the average recoveries were 89.8-103.3% with a relative standard deviation (RSD) <6.5%, demonstrating the successful application in real sample analysis. PMID- 26851452 TI - Adsorption of T4 bacteriophages on planar indium tin oxide surface via controlled surface tailoring. AB - The work investigates the influence of surface physicochemical properties of planar indium tin oxide (ITO) as a model substrate on T4 bacteriophage adsorption. A comparative T4 bacteriophage adsorption study shows a significant difference in bacteriophage adsorption observed on chemically modified planar ITO when compared to similarly modified particulate ITO, which infers that trends observed in virus-particle interaction studies are not necessarily transferrable to predict virus-planar surface adsorption behaviour. We also found that ITO surfaces modified with methyl groups, (resulting in increased surface roughness and hydrophobicity) remained capable of adsorbing T4 bacteriophage. The adsorption of T4 onto bare, amine and carboxylic functionalised planar ITO suggests the presence of a unique binding behaviour involving specific functional groups on planar ITO surface beyond the non-specific electrostatic interactions that dominate phage to particle interactions. The paper demonstrates the significance of physicochemical properties of surfaces on bacteriophage-surface interactions. PMID- 26851453 TI - Highly active carbon supported ternary PdSnPtx (x=0.1-0.7) catalysts for ethanol electro-oxidation in alkaline and acid media. AB - A series of trimetallic PdSnPtx (x=0.1-0.7)/C catalysts with varied Pt content have been synthesized by co-reduction method using NaBH4 as a reducing agent. These catalysts were characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV) and chronoamperometry (CA). The electrochemical results show that, after adding a minor amount of Pt dopant, the resultant PdSnPtx/C demonstrated more superior catalytic performance toward ethanol oxidation as compared with that of mono-/bi-metallic Pd/C or PdSn/C in alkaline solution and the PdSnPt0.2/C with optimal molar ratio reached the best. In acid solution, the PdSnPt0.2/C also depicted a superior catalytic activity relative to the commercial Pt/C catalyst. The possible enhanced synergistic effect between Pd, Sn/Sn(O) and Pt in an alloyed state should be responsible for the as-revealed superior ethanol electro-oxidation performance based upon the beneficial electronic effect and bi-functional mechanism. It implies the trimetallic PdSnPt0.2/C with a low Pt content has a promising prospect as anodic electrocatalyst in fields of alkali- and acid-type direct ethanol fuel cells. PMID- 26851454 TI - Facile synthesis of 3D porous thermally exfoliated g-C3N4 nanosheet with enhanced photocatalytic degradation of organic dye. AB - 3D porous framework composed of exfoliated ultrathin nanosheets is a hot topic in the field of energy storage and conversion. A facile method to prepare 3D mesoporous C3N4 with few-layered nanosheets interconnected in large quantity via H2SO4 intercalation and subsequent thermal treatment was described herein. The obtained thermally-exfoliated C3N4 (TE-C3N4) was thoroughly characterized by scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FTIR) spectroscopy, atomic force microscopy (AFM), UV-Vis diffuse reflectance spectroscopy (DRS) and Brunauer Emmett-Teller (BET) measurements. The detailed analysis indicated that TE-C3N4 possessed enlarged inter-layer space, enhanced UV-light adsorption and high specific surface area with 3D interconnected structure composed of ultrathin 2D nanosheets. Compared to bulk C3N4, TE-C3N4 showed an enhanced photocatalytic activity for photodegradation of Rhodamine B under UV-light irradiation and exhibited no significant loss of photocatalytic activity after 11 recycled runs. The pseudo-first reaction rate constant for TE-C3N4 was about four times higher than that for pure bulk-C3N4. The better photocatalytic performance could be attributed to more active catalytic sites, prolonged photo-excited carrier lifetime and shorted pathway of the carriers to the reaction sites. PMID- 26851455 TI - Mate-choice copying in Drosophila melanogaster: Impact of demonstration conditions and male-male competition. AB - Individuals of many species, including invertebrates, have been shown to use social information in mate choice, notably by extracting information from the mating performance of opposite sex conspecifics, a process called "mate-choice copying" (MCC). Here, we performed four experiments with Drosophila melanogaster to investigate two aspects of MCC methodology: whether (i) providing positive and negative social information simultaneously or sequentially during the demonstration phase of the protocol, and (ii) male-male competition during the mate-choice test, affect MCC. We found that the simultaneous provision of positive and negative information during demonstrations hampered female MCC performance, compared to the sequential provision of information. This can be interpreted in two alternative, yet not exclusive, ways: (i) attentional mechanisms may restrict the focus of the brain to one source of information at a time, and/or (ii) the shorter duration of demonstrations in the simultaneous protocol may have not permit full social learning use and may explain the non detection of MCC in that protocol. Moreover, we did not detect any significant effect of male-male competition on female choice. This study thus provides further evidence for MCC in D. melanogaster and expands on the necessary methodology for detailed studies. PMID- 26851456 TI - Plastic pikas: Behavioural flexibility in low-elevation pikas (Ochotona princeps). AB - Behaviour is an important mechanism for accommodating rapid environmental changes. Understanding a species' capacity for behavioural plasticity is therefore a key, but understudied, aspect of developing tractable conservation and management plans under climate-change scenarios. Here, we quantified behavioural differences between American pikas (Ochotona princeps) living in an atypical, low-elevation habitat versus those living in a more-typical, alpine habitat. With respect to foraging strategy, low-elevation pikas spent more time consuming vegetation and less time caching food for winter, compared to high elevation pikas. Low-elevation pikas were also far more likely to be detected in forested microhabitats off the talus than their high-elevation counterparts at midday. Finally, pikas living in the atypical habitat had smaller home range sizes compared to those in typical habitat or any previously published home ranges for this species. Our findings indicate that behavioural plasticity likely allows pikas to accommodate atypical conditions in this low-elevation habitat, and that they may rely on critical habitat factors such as suitable microclimate refugia to behaviourally thermoregulate. Together, these results suggest that behavioural adjustments are one important mechanism by which pikas can persist outside of their previously appreciated dietary and thermal niches. PMID- 26851457 TI - Reduced glutathione biosynthesis in Drosophila melanogaster causes neuronal defects linked to copper deficiency. AB - Glutathione (GSH) is a tripeptide often considered to be the master antioxidant in cells. GSH plays an integral role in cellular redox regulation and is also known to have a role in mammalian copper homeostasis. In vitro evidence suggests that GSH is involved in copper uptake, sequestration and efflux. This study was undertaken to further investigate the roles that GSH plays in neuronal copper homeostasis in vivo, using the model organism Drosophila melanogaster. RNA interference-mediated knockdown of the Glutamate-cysteine ligase catalytic subunit gene (Gclc) that encodes the rate-limiting enzyme in GSH biosynthesis was utilised to genetically deplete GSH levels. When Gclc was knocked down in all neurons, this caused lethality, which was partially rescued by copper supplementation and was exacerbated by additional knockdown of the copper uptake transporter Ctr1A, or over-expression of the copper efflux transporter ATP7. Furthermore, when Gclc was knocked down in a subset of neuropeptide-producing cells, this resulted in adult progeny with unexpanded wings, a phenotype previously associated with copper dyshomeostasis. In these cells, Gclc suppression caused a decrease in axon branching, a phenotype further enhanced by ATP7 over-expression. Therefore, we conclude that GSH may play an important role in regulating neuronal copper levels and that reduction in GSH may lead to functional copper deficiency in neurons in vivo. We provide genetic evidence that glutathione (GSH) levels influence Cu content or distribution in vivo, in Drosophila neurons. GSH could be required for binding Cu imported by Ctr1A and distributing it to chaperones, such as Mtn, CCS and Atox1. Alternatively, GSH could modify the copper-binding and transport activities of Atox1 and the ATP7 efflux protein via glutathionylation of copper-binding cysteines. PMID- 26851458 TI - The impact of user- and system-initiated personalization on the user experience at large sports events. AB - This article describes an experimental study investigating the impact on user experience of two approaches of personalization of content provided on a mobile device, for spectators at large sports events. A lab-based experiment showed that a system-driven approach to personalization was generally preferable, but that there were advantages to retaining some user control over the process. Usability implications for a hybrid approach, and design implications are discussed, with general support for countermeasures designed to overcome recognised limitations of adaptive systems. PMID- 26851459 TI - Building healthy construction workers: Their views on health, wellbeing and better workplace design. AB - Construction is a heavy manual industry where working into later life can be a challenge. An interview study was conducted to explore workers' understanding of their health at work and ways of making their jobs easier, safer or more comfortable. Using purposive sampling, 80 trades' workers were selected from construction sites in the UK. The Nordic Musculoskeletal Questionnaire and Work Ability Index were used to explore aches and pains and reducing strain on the body. A high prevalence of symptoms was reported and ratings of work ability were high. Workers were aware of the physical demands of their work and had over 250 ideas around health and wellbeing e.g. rucksacks for tools, bespoke benches, adapting PPE, and higher cost solutions e.g. mechanical lifting aids. Engagement of the workforce should be encouraged and feed into change processes in the industry to enable all workers stay fit for work for longer. PMID- 26851460 TI - A macroergonomic perspective on fatigue and coping in the hospital nurse work system. AB - Occupational fatigue in hospital nurses is associated with increased nurse turnover, and decreased nurse health and patient safety. The goal of this study was to explore the factors contributing to or preventing fatigue, and barriers and facilitators to individual nurse coping in hospital work systems. Interviews were conducted and analyzed using a directed qualitative content analysis approach guided by the Systems Engineering Initiative for Patient Safety (SEIPS) model. Themes related to sources of fatigue within each of the five primary components of the SEIPS work system were identified, along with barriers and facilitators to nurses' experiences and strategies for coping with fatigue. Findings from this study provide guidance on what nurses perceive as contributing to fatigue and factors that are helpful and harmful to coping with fatigue within their work system. Implications for fatigue risk management systems (FRMS) are also discussed, in particular the importance of maintaining nurse autonomy in decision-making when implementing fatigue interventions or countermeasures. PMID- 26851461 TI - Effect of cardboard under a sleeping bag on sleep stages during daytime nap. AB - Fourteen healthy male subjects slept from 13:30 to 15:30 under ambient temperature and relative humidity maintained at 15 degrees C and 60%, respectively. They slept under two conditions: in a sleeping bag on wooden flooring (Wood) and in a sleeping bag with corrugated cardboard between the bag and the flooring (CC). Polysomnography, skin temperature (Tsk), microclimate, bed climate, and subjective sensations were obtained. The number of awakenings in the CC had significantly decreased compared to that in the Wood. The mean, back, and thigh Tsk, and bed climate temperature were significantly higher in the CC than that in the Wood. Subjective thermal sensations were warmer in the CC than in the Wood. These results suggest that using corrugated cardboard under a sleeping bag may reduce cold stress, thereby decreasing the number of awakenings and increasing subjective warmth; the mean, back, and thigh Tsk; and bed climate temperature. PMID- 26851462 TI - Evaluating the ability of novices to identify and quantify physical demand elements following an introductory education session: A pilot study. AB - A Physical Demands Description (PDD) is a resource that describes the physical demands of a job in a systematic way. PDD data are commonly used to make legal, medical, and monetary decisions related to work. Despite the fundamental importance of a PDD, data are often gathered by novice or early career ergonomists, where we have limited knowledge regarding their proficiency in performing PDDs. The purpose of this pilot study was to evaluate novices' proficiency in identifying and quantifying physical demands elements embedded within three job simulations, following a formal PDD education session. The education session was based on the revised Occupational Health Clinics for Ontario Workers (OHCOW, 2014) PDD Handbook. Participants were able to identify physical demands elements with an average success rate of 80%, but were often unable to accurately quantify measures related to each element within a prescribed error threshold of 10%. These data suggest that practitioners should exercise caution when sending novice ergonomists out on their own to complete PDDs. PMID- 26851463 TI - Age and work environment characteristics in relation to sleep: Additive, interactive and curvilinear effects. AB - Although additive combinations of age and work environment characteristics have been found to predict sleep impairment, possible age x work environment interactions have been largely disregarded. The present study examined linear and curvilinear interactions of age with work environment measures in relation to sleep quality and duration. Survey data were collected from offshore day-shift personnel (N = 901). Main effects and interactions of the age terms with work environment measures (job demand, control, and social support, physical environment and strenuous work) were evaluated. Sleep duration was predicted by a curvilinear interaction, age(2) x job demand (p < .005), and by the age x social support interaction (p < .002); sleep quality was predicted by age x job demand (p < .002). Job control and physical environment showed significant additive effects. At a time when older employees are encouraged to remain in the workforce, the findings serve to increase understanding of how ageing and work demands jointly contribute to sleep impairment. PMID- 26851464 TI - Discomfort of seated persons exposed to low frequency lateral and roll oscillation: Effect of backrest height. AB - Backrests influence the comfort of seated people. With 21 subjects sitting with three backrest heights (no backrest, short backrest, high backrest) discomfort caused by lateral, roll, and fully roll-compensated lateral oscillation was investigated at frequencies between 0.25 and 1.0 Hz. With lateral oscillation, the short backrest reduced discomfort at frequencies less than 0.63 Hz and the high backrest reduced discomfort at frequencies less than 1.0 Hz. With roll oscillation, the high backrest reduced discomfort at frequencies less than 0.63 Hz, but increased discomfort at 1.0 Hz. With fully roll-compensated lateral oscillation, the short backrest reduced discomfort at 0.4 Hz and the high backrest reduced discomfort at 0.5 and 0.63 Hz. As predicted by current standards, a backrest can increase discomfort caused by high frequencies of vibration. However, a backrest can reduce discomfort caused by low frequencies, with the benefit depending on the frequency and direction of oscillation and backrest height. PMID- 26851465 TI - Personal and other factors affecting acceptance of smartphone technology by older Chinese adults. AB - It has been well documented that in the 21st century, there will be relatively more older people around the world than in the past. Also, it seems that technology will expand in this era at an unprecedented rate. Therefore, it is of critical importance to understand the factors that influence the acceptance of technology by older people. The positive impact that the use of mobile applications can have for older people was confirmed by a previous study (Plaza et al., 2011). The study reported here aimed to explore and confirm, for older adults in China, the key influential factors of smartphone acceptance, and to describe the personal circumstances of Chinese older adults who use smartphone. A structured questionnaire and face to face individual interviews were used with 120 Chinese older adults (over 55). Structural Equation Modeling was used to confirm a proposed smartphone acceptance model based on Technology Acceptance Model (TAM), and the Unified Theory of Acceptance and Use of Technology (UTAUT). The results showed that those who were younger, with higher education, non widowed, with better economic condition related to salary or family support were more likely to use smartphone. Also, cost was found to be a critical factor influencing behavior intention. Self-satisfaction and facilitating conditions were proved to be important factors influencing perceived usefulness and perceived ease of use. PMID- 26851466 TI - The effect of split sleep schedules (6h-on/6h-off) on neurobehavioural performance, sleep and sleepiness. AB - Shorter, more frequent rosters, such as 6h-on/6h-off split shifts, may offer promise to sleep, subjective sleepiness and performance by limiting shift length and by offering opportunities for all workers to obtain some sleep across the biological night. However, there exists a paucity of studies that have examined these shifts using objective measures of sleep and performance. The present study examined neurobehavioural performance, sleepiness and sleep during 6h-on/6h-off split sleep schedules. Sixteen healthy adults (6 males, 26.13 y +/- 4.46) participated in a 9-day laboratory study that included two baseline nights (BL, 10h time in bed (TIB), 2200 h-0800 h), 4 days on one of two types of 6h-on/6h-off split sleep schedules with 5h TIB during each 'off' period (6h early: TIB 0300 h 0800 h and 1500 h-20000 h, or 6-h late: TIB 0900 h-1400 h and 2100 h-0200 h), and two recovery nights (10h TIB per night, 2200 h-0800 h). Participants received 10h TIB per 24h in total across both shift schedules. A neurobehavioural test bout was completed every 2 h during wake, which included the Psychomotor Vigilance Task (PVT) and the Karolinska Sleepiness Scale (KSS). Linear mixed effects models were used to assess the effect of day (BL, shift days 1-4), schedule (6h early, 6h late) and trial (numbers 1-6) on PVT lapses (operationalised as the number of reaction times >500 ms), PVT total lapse time, PVT fastest 10% of reaction times and KSS. Analyses were also conducted examining the effect of day and schedule on sleep variables. Overall, PVT lapses and total lapse time did not differ significantly between baseline and shift days, however, peak response speeds were significantly slower on the first shift day when compared to baseline, but only for those in the 6h-late condition. Circadian variations were apparent in performance outcomes, with individuals in the 6h-late condition demonstrated significantly more and longer lapses and slower peak reaction times at the end of their night shift (0730 h) than at any other time during their shifts. In the 6h early condition, only response speed significantly differed across trials, with slower response speeds occurring at trial 1 (0930 h) than in trials 3 (1330 h) or 4 (2130 h). While subjective sleepiness was higher on shift days than at baseline, sleepiness did not accumulate across days. Total sleep was reduced across split sleep schedules compared to baseline. Overall, these results show that while there was not a cumulative cost to performance across days of splitting sleep, participants obtained less sleep and reported lowered alertness on shift days. Tests near the circadian nadir showed higher sleepiness and increased performance deficits. While this schedule did not produce cumulative impairment, the performance deficits witnessed during the biological night are still of operational concern for industry and workers alike. PMID- 26851467 TI - Active workstation allows office workers to work efficiently while sitting and exercising moderately. AB - OBJECTIVE: To determine the effects of a moderate-intensity active workstation on time and error during simulated office work. METHODS: The aim of the study was to analyse simultaneous work and exercise for non-sedentary office workers. We monitored oxygen uptake, heart rate, sweating stains area, self-perceived effort, typing test time with typing error count and cognitive performance during 30 min of exercise with no cycling or cycling at 40 and 80 W. RESULTS: Compared baseline, we found increased physiological responses at 40 and 80 W, which corresponds to moderate physical activity (PA). Typing time significantly increased by 7.3% (p = 0.002) in C40W and also by 8.9% (p = 0.011) in C80W. Typing error count and cognitive performance were unchanged. CONCLUSIONS: Although moderate intensity exercise performed on cycling workstation during simulated office tasks increases working task execution time with, it has moderate effect size; however, it does not increase the error rate. Participants confirmed that such a working design is suitable for achieving the minimum standards for daily PA during work hours. PMID- 26851469 TI - A methodology using in-chair movements as an objective measure of discomfort for the purpose of statistically distinguishing between similar seat surfaces. AB - This study presents a method for objectively measuring in-chair movement (ICM) that shows correlation with subjective ratings of comfort and discomfort. Employing a cross-over controlled, single blind design, healthy young subjects (n = 21) sat for 18 min on each of the following surfaces: contoured foam, straight foam and wood. Force sensitive resistors attached to the sitting interface measured the relative movements of the subjects during sitting. The purpose of this study was to determine whether ICM could statistically distinguish between each seat material, including two with subtle design differences. In addition, this study investigated methodological considerations, in particular appropriate threshold selection and sitting duration, when analysing objective movement data. ICM appears to be able to statistically distinguish between similar foam surfaces, as long as appropriate ICM thresholds and sufficient sitting durations are present. A relationship between greater ICM and increased discomfort, and lesser ICM and increased comfort was also found. PMID- 26851468 TI - Assessing attentional prioritization of front-of-pack nutrition labels using change detection. AB - We used a change detection method to evaluate attentional prioritization of nutrition information that appears in the traditional "Nutrition Facts Panel" and in front-of-pack nutrition labels. Results provide compelling evidence that front of-pack labels attract attention more readily than the Nutrition Facts Panel, even when participants are not specifically tasked with searching for nutrition information. Further, color-coding the relative nutritional value of key nutrients within the front-of-pack label resulted in increased attentional prioritization of nutrition information, but coding using facial icons did not significantly increase attention to the label. Finally, the general pattern of attentional prioritization across front-of-pack designs was consistent across a diverse sample of participants. Our results indicate that color-coded, front-of pack nutrition labels increase attention to the nutrition information of packaged food, a finding that has implications for current policy discussions regarding labeling change. PMID- 26851470 TI - Time pressure and regulations on hospital-in-the-home (HITH) nurses: An on-the road study. AB - This study investigated both causal factors and consequences of time pressure in hospital-in-the-home (HITH) nurses. These nurses may experience additional stress from the time pressure they encounter while driving to patients' homes, which may result in greater risk taking while driving. From observation in natural settings, data related to the nurses' driving behaviours and emotions were collected and analysed statistically; semi-directed interviews with the nurses were analysed qualitatively. The results suggest that objective time constraints alone do not necessarily elicit subjective time pressure. The challenges and uncertainty associated with healthcare and the driving period contribute to the emergence of this time pressure, which has a negative impact on both the nurses' driving and their emotions. Finally, the study focuses on anticipated and in situ regulations. These findings provide guidelines for organizational and technical solutions allowing the reduction of time pressure among HITH nurses. PMID- 26851471 TI - Musculoskeletal disorders in construction: A review and a novel system for activity tracking with body area network. AB - Human body motions have been analysed for decades with a view on enhancing occupational well-being and performance of workers. On-going progresses in miniaturised wearable sensors are set to revolutionise biomechanical analysis by providing accurate and real-time quantitative motion data. The construction industry has a poor record of occupational health, in particular with regard to work-related musculoskeletal disorders (WMSDs). In this article, we therefore focus on the study of human body motions that could cause WMSDs in construction related activities. We first present an in-depth review of existing assessment frameworks used in practice for the evaluation of human body motion. Subsequently different methods for measuring working postures and motions are reviewed and compared, pointing out the technological developments, limitations and gaps; Inertial Measurement Units (IMUs) are particularly investigated. Finally, we introduce a new system to detect and characterise unsafe postures of construction workers based on the measurement of motion data from wearable wireless IMUs integrated in a body area network. The potential of this system is demonstrated through experiments conducts in a laboratory as well as in a college with actual construction trade trainees. PMID- 26851472 TI - Physical exercise and burnout facets predict injuries in a population-based sample of French career firefighters. AB - Although firefighting is known to engender a high rate of injury, few studies have examined the contribution of physical exercise, burnout and coping strategies to firefighting-related injuries. Data were collected from a population-based sample of 220 male firefighters. In a descriptive study, the nature and site of the injuries and the relationships among firefighter injuries, physical exercise, burnout and coping strategies were examined. Sprains were the most prevalent type of injury (98%), followed by tendinitis (40%) and muscle tears (30%). More than two thirds of these injuries were located at the ankle. Weekly hours of physical exercise, cognitive weariness at work, social support seeking, problem-focused coping and emotional exhaustion were significantly related to these injuries. The findings suggest that physical exercise and cognitive weariness can be considered as risk factors for French firefighter injuries, whereas problem-focused coping can be seen as a protective factor. More research is needed to explain the relationship between social support seeking and injury. PMID- 26851473 TI - Latent human error analysis and efficient improvement strategies by fuzzy TOPSIS in aviation maintenance tasks. AB - The purposes of this study were to develop a latent human error analysis process, to explore the factors of latent human error in aviation maintenance tasks, and to provide an efficient improvement strategy for addressing those errors. First, we used HFACS and RCA to define the error factors related to aviation maintenance tasks. Fuzzy TOPSIS with four criteria was applied to evaluate the error factors. Results show that 1) adverse physiological states, 2) physical/mental limitations, and 3) coordination, communication, and planning are the factors related to airline maintenance tasks that could be addressed easily and efficiently. This research establishes a new analytic process for investigating latent human error and provides a strategy for analyzing human error using fuzzy TOPSIS. Our analysis process complements shortages in existing methodologies by incorporating improvement efficiency, and it enhances the depth and broadness of human error analysis methodology. PMID- 26851474 TI - Removing the thermal component from heart rate provides an accurate VO2 estimation in forest work. AB - Heart rate (HR) was monitored continuously in 41 forest workers performing brushcutting or tree planting work. 10-min seated rest periods were imposed during the workday to estimate the HR thermal component (DeltaHRT) per Vogt et al. (1970, 1973). VO2 was measured using a portable gas analyzer during a morning submaximal step-test conducted at the work site, during a work bout over the course of the day (range: 9-74 min), and during an ensuing 10-min rest pause taken at the worksite. The VO2 estimated, from measured HR and from corrected HR (thermal component removed), were compared to VO2 measured during work and rest. Varied levels of HR thermal component (DeltaHRTavg range: 0-38 bpm) originating from a wide range of ambient thermal conditions, thermal clothing insulation worn, and physical load exerted during work were observed. Using raw HR significantly overestimated measured work VO2 by 30% on average (range: 1%-64%). 74% of VO2 prediction error variance was explained by the HR thermal component. VO2 estimated from corrected HR, was not statistically different from measured VO2. Work VO2 can be estimated accurately in the presence of thermal stress using Vogt et al.'s method, which can be implemented easily by the practitioner with inexpensive instruments. PMID- 26851475 TI - Classifying work rate from heart rate measurements using an adaptive neuro-fuzzy inference system. AB - In a new approach based on adaptive neuro-fuzzy inference systems (ANFIS), field heart rate (HR) measurements were used to classify work rate into four categories: very light, light, moderate, and heavy. Inter-participant variability (physiological and physical differences) was considered. Twenty-eight participants performed Meyer and Flenghi's step-test and a maximal treadmill test, during which heart rate and oxygen consumption (VO2) were measured. Results indicated that heart rate monitoring (HR, HRmax, and HRrest) and body weight are significant variables for classifying work rate. The ANFIS classifier showed superior sensitivity, specificity, and accuracy compared to current practice using established work rate categories based on percent heart rate reserve (%HRR). The ANFIS classifier showed an overall 29.6% difference in classification accuracy and a good balance between sensitivity (90.7%) and specificity (95.2%) on average. With its ease of implementation and variable measurement, the ANFIS classifier shows potential for widespread use by practitioners for work rate assessment. PMID- 26851476 TI - Thermal sensations and comfort investigations in transient conditions in tropical office. AB - The study was done to identify affective and sensory responses observed as a result of hysteresis effects in transient thermal conditions consisting of warm neutral and neutral - warm performed in a quasi-experiment setting. Air conditioned building interiors in hot-humid areas have resulted in thermal discomfort and health risks for people moving into and out of buildings. Reports have shown that the instantaneous change in air temperature can cause abrupt thermoregulation responses. Thermal sensation vote (TSV) and thermal comfort vote (TCV) assessments as a consequence of moving through spaces with distinct thermal conditions were conducted in an existing single-story office in a hot-humid microclimate, maintained at an air temperature 24 degrees C (+/- 0.5), relative humidity 51% (+/- 7), air velocity 0.5 m/s (+/- 0.5), and mean radiant temperature (MRT) 26.6 degrees C (+/- 1.2). The measured office is connected to a veranda that showed the following semi-outdoor temperatures: air temperature 35 degrees C (+/- 2.1), relative humidity 43% (+/- 7), air velocity 0.4 m/s (+/- 0.4), and MRT 36.4 degrees C (+/- 2.9). Subjective assessments from 36 college aged participants consisting of thermal sensations, preferences and comfort votes were correlated against a steady state predicted mean vote (PMV) model. Local skin temperatures on the forehead and dorsal left hand were included to observe physiological responses due to thermal transition. TSV for veranda-office transition showed that no significant means difference with TSV office-veranda transition were found. However, TCV collected from warm-neutral (-0.24, +/- 1.2) and neutral-warm (-0.72, +/- 1.3) conditions revealed statistically significant mean differences (p < 0.05). Sensory and affective responses as a consequence of thermal transition after travel from warm-neutral-warm conditions did not replicate the hysteresis effects of brief, slightly cool, thermal sensations found in previous laboratory experiments. These findings also indicate that PMV is an acceptable alternative to predict thermal sensation immediately after a down-step thermal transition (<= 1 min exposure duration) for people living in a hot-humid climate country. PMID- 26851477 TI - Anthropometric characteristics of female smallholder farmers of Uganda--Toward design of labor-saving tools. AB - Sub-Saharan African women on small-acreage farms carry a disproportionately higher labor burden, which is one of the main reasons they are unable to produce for both home and the market and realize higher incomes. Labor-saving interventions such as hand-tools are needed to save time and/or increase productivity in, for example, land preparation for crop and animal agriculture, post-harvest processing, and meeting daily energy and water needs. Development of such tools requires comprehensive and content-specific anthropometric data or body dimensions and existing databases based on Western women may be less relevant. We conducted measurements on 89 women to provide preliminary results toward answering two questions. First, how well existing databases are applicable in the design of hand-tools for sub-Saharan African women. Second, how universal body dimension predictive models are among ethnic groups. Our results show that, body dimensions between Bantu and Nilotic ethnolinguistic groups are different and both are different from American women. These results strongly support the need for establishing anthropometric databases for sub-Saharan African women, toward hand-tool design. PMID- 26851478 TI - Sex-based differences in lifting technique under increasing load conditions: A principal component analysis. AB - The objective of the present study was to determine if there is a sex-based difference in lifting technique across increasing-load conditions. Eleven male and 14 female participants (n = 25) with no previous history of low back disorder participated in the study. Participants completed freestyle, symmetric lifts of a box with handles from the floor to a table positioned at 50% of their height for five trials under three load conditions (10%, 20%, and 30% of their individual maximum isometric back strength). Joint kinematic data for the ankle, knee, hip, and lumbar and thoracic spine were collected using a two-camera Optotrak motion capture system. Joint angles were calculated using a three-dimensional Euler rotation sequence. Principal component analysis (PCA) and single component reconstruction were applied to assess differences in lifting technique across the entire waveforms. Thirty-two PCs were retained from the five joints and three axes in accordance with the 90% trace criterion. Repeated-measures ANOVA with a mixed design revealed no significant effect of sex for any of the PCs. This is contrary to previous research that used discrete points on the lifting curve to analyze sex-based differences, but agrees with more recent research using more complex analysis techniques. There was a significant effect of load on lifting technique for five PCs of the lower limb (PC1 of ankle flexion, knee flexion, and knee adduction, as well as PC2 and PC3 of hip flexion) (p < 0.005). However, there was no significant effect of load on the thoracic and lumbar spine. It was concluded that when load is standardized to individual back strength characteristics, males and females adopted a similar lifting technique. In addition, as load increased male and female participants changed their lifting technique in a similar manner. PMID- 26851479 TI - Driving while using a smartphone-based mobility application: Evaluating the impact of three multi-choice user interfaces on visual-manual distraction. AB - Innovative in-car applications provided on smartphones can deliver real-time alternative mobility choices and subsequently generate visual-manual demand. Prior studies have found that multi-touch gestures such as kinetic scrolling are problematic in this respect. In this study we evaluate three prototype tasks which can be found in common mobile interaction use-cases. In a repeated-measures design, 29 participants interacted with the prototypes in a car-following task within a driving simulator environment. Task completion, driving performance and eye gaze have been analysed. We found that the slider widget used in the filtering task was too demanding and led to poor performance, while kinetic scrolling generated a comparable amount of visual distraction despite it requiring a lower degree of finger pointing accuracy. We discuss how to improve continuous list browsing in a dual-task context. PMID- 26851480 TI - Predicting tool operator capacity to react against torque within acceptable handle deflection limits in automotive assembly. AB - The proportion of tool operators capable of maintaining published psychophysically derived threaded fastener tool handle deflection limits were predicted using a biodynamic tool operator model, interacting with the tool, task and workstation. Tool parameters, including geometry, speed and torque were obtained from the specifications for 35 tools used in an auto assembly plant. Tool mass moments of inertia were measured for these tools using a novel device that engages the tool in a rotating system of known inertia. Task parameters, including fastener target torque and joint properties (soft, medium or hard), were ascertained from the vehicle design specifications. Workstation parameters, including vertical and horizontal distances from the operator were measured using a laser rangefinder for 69 tool installations in the plant. These parameters were entered into the model and tool handle deflection was predicted for each job. While handle deflection for most jobs did not exceed the capacity of 75% females and 99% males, six jobs exceeded the deflection criterion. Those tool installations were examined and modifications in tool speed and operator position improved those jobs within the deflection limits, as predicted by the model. We conclude that biodynamic tool operator models may be useful for identifying stressful tool installations and interventions that bring them within the capacity of most operators. PMID- 26851481 TI - The effects of a passive exoskeleton on muscle activity, discomfort and endurance time in forward bending work. AB - Exoskeletons may form a new strategy to reduce the risk of developing low back pain in stressful jobs. In the present study we examined the potential of a so called passive exoskeleton on muscle activity, discomfort and endurance time in prolonged forward-bended working postures. Eighteen subjects performed two tasks: a simulated assembly task with the trunk in a forward-bended position and static holding of the same trunk position without further activity. We measured the electromyography for muscles in the back, abdomen and legs. We also measured the perceived local discomfort. In the static holding task we determined the endurance, defined as the time that people could continue without passing a specified discomfort threshold. In the assembly task we found lower muscle activity (by 35-38%) and lower discomfort in the low back when wearing the exoskeleton. Additionally, the hip extensor activity was reduced. The exoskeleton led to more discomfort in the chest region. In the task of static holding, we observed that exoskeleton use led to an increase in endurance time from 3.2 to 9.7 min, on average. The results illustrate the good potential of this passive exoskeleton to reduce the internal muscle forces and (reactive) spinal forces in the lumbar region. However, the adoption of an over-extended knee position might be, among others, one of the concerns when using the exoskeleton. PMID- 26851482 TI - Work system barriers to patient, provider, and caregiver use of personal health records: A systematic review. AB - OBJECTIVES: This review applied a human factors/ergonomics (HF/E) paradigm to assess individual, work system/unit, organization, and external environment factors generating barriers to patient, provider, and informal caregiver personal health record (PHR) use. METHODS: The literature search was conducted using five electronic databases for the timeframe January 2000 to October 2013, resulting in 4865 citations. Two authors independently coded included articles (n = 60). RESULTS: Fifty-five, ten and five articles reported barriers to patient, provider and caregiver PHR use, respectively. Barriers centered around 20 subfactors. The most frequently noted were needs, biases, beliefs, and mood (n = 35) and technology functions and features (n = 32). CONCLUSIONS: The HF/E paradigm was effective in framing the assessment of factors creating barriers to PHR use. Design efforts should address literacy, interoperability, access to health information, and secure messaging. A deeper understanding of the interactions between work systems and the role of organization and external environment factors is required. PMID- 26851483 TI - Working postures and physical activity among registered nurses. AB - Nurses report a high prevalence of musculoskeletal discomfort, particularly of the low back and neck/shoulder. This study characterized the full-shift upper arm and trunk postures and movement velocities of registered nurses using inertial measurement units (IMUs). Intensity of occupational physical activity (PA) was also ascertained using a waist-worn PA monitor and using the raw acceleration data from each IMU. Results indicated that nurses spent a relatively small proportion of their work time with the arms or trunk in extreme postures, but had few opportunities for rest and recovery in comparison to several other occupational groups. Comparisons between nurses in different PA groups suggested that using a combination of accelerometers secured to several body locations may provide more representative estimates of physical demands than a single, waist worn PA monitor. The findings indicate a need for continued field-based research with larger sample sizes to facilitate the development of maximally effective intervention strategies. PMID- 26851484 TI - Mup-knockout mice generated through CRISPR/Cas9-mediated deletion for use in urinary protein analysis. AB - Major urinary proteins (MUPs) are the most abundant protein species in mouse urine, accounting for more than 90% of total protein content. Twenty-one Mup genes and 21 pseudogenes are clustered in a region of around 2 megabase pairs (Mbp) on chromosome 4. A Mup-knockout mouse model would greatly facilitate researches in the field of proteomic analysis of mouse urine. Here, we report the successful knockout of the Mup gene cluster of 2.2 Mbp using the CRISPR/Cas9 system. Homozygous Mup-knockout mice survived to adulthood and exhibited no obvious defects. The patterns of the proteomes of non-MUP urinary proteins in homozygous Mup-knockout mice were similar to those of wild-type mice judged by sodium dodecyl sulfate polyacrylamide gel electrophoresis. The sensitivity of enzyme-linked immunosorbent assay to detect non-MUP urinary protein was significantly enhanced in Mup-knockout mice. In short, we have developed a Mup knockout mouse model. This mouse model will be useful for the research of urinary biomarker testing that may have relevance for humans. PMID- 26851487 TI - The use of quality metrics in health care: primum non nocere and the law of unintended consequences. PMID- 26851485 TI - Glial coverage in the optic nerve expands in proportion to optic axon loss in chronic mouse glaucoma. AB - Within the white matter, axonal loss by neurodegeneration is coupled to glial cell changes in gene expression, structure and function commonly termed gliosis. Recently, we described the highly variable expansion of gliosis alebosco@neuro.utah.edu in degenerative optic nerves from the DBA/2J mouse model of chronic, age-related glaucoma. Here, to estimate and compare the levels of axonal loss with the expansion of glial coverage and axonal degeneration in DBA/2J nerves, we combined semiautomatic axon counts with threshold-based segmentation of total glial/scar areas and degenerative axonal profiles in plastic cross-sections. In nerves ranging from mild to severe degeneration, we found that the progression of axonal dropout is coupled to an increase of gliotic area. We detected a strong correlation between axon loss and the aggregate coverage by glial cells and scar, whereas axon loss did not correlate with the small fraction of degenerating profiles. Nerves with low to medium levels of axon loss displayed moderate glial reactivity, consisting of hypertrophic astrocytes, activated microglia and normal distribution of oligodendrocytes, with minimal reorganization of the tissue architecture. In contrast, nerves with extensive axonal loss showed prevalent rearrangement of the nerve, with loss of axon fascicle territories and enlarged or almost continuous gliotic and scar domains, containing reactive astrocytes, oligodendrocytes and activated microglia. These findings support the value of optic nerve gliotic expansion as a quantitative estimate of optic neuropathy that correlates with axon loss, applicable to grade the severity of optic nerve damage in mouse chronic glaucoma. PMID- 26851486 TI - Glycan involvement in the adhesion of Pseudomonas aeruginosa to tears. AB - The human eye is constantly bathed by tears, which protect the ocular surface via a variety of mechanisms. The O-linked glycans of tear mucins have long been considered to play a role in binding to pathogens and facilitating their removal in the tear flow. Other conjugated glycans in tears could similarly contribute to pathogen binding and removal but have received less attention. In the work presented here we assessed the contribution of glycan moieties, in particular the protein attached N-glycans, presented by the broad complement of tear proteins to the adhesion of the opportunistic pathogen Pseudomonas aeruginosa, a leading cause of microbial keratitis and ulceration of the cornea. Our adhesion assay involved immobilising the macromolecular components of tears into the wells of a polyvinyl difluoride (PVDF) microtitre filter plate and probing the binding of fluorescently labelled bacteria. Three P. aeruginosa strains were studied: a cytotoxic strain (6206) and an invasive strain (6294) from eye infections, and an invasive strain (320) from a urinary tract infection (UTI). The ocular isolates adhered two to three times more to human tears than to human saliva or porcine gastric mucin, suggesting ocular niche-specific adaptation. Support for the role of the N-glycans carried by human tear proteins in the binding and removal of P. aeruginosa from the eye was shown by: 1) pre-incubation of the bacteria with free component sugars, galactose, mannose, fucose and sialyl lactose (or combination thereof) inhibiting adhesion of all the P. aeruginosa strains to the immobilised tear proteins, with the greatest inhibition of binding of the ocular cytotoxic 6206 and least for the invasive 6294 strain; 2) pre-incubation of the bacteria with N-glycans released from the commercially available human milk lactoferrin, an abundant protein that carries N-linked glycans in tears, inhibiting the adhesion to tears of the ocular bacteria by up to 70%, which was significantly more binding inhibition than by the same amount of intact human lactoferrin or by the plant-derived N-glycans released from the rice recombinant lactoferrin; 3) pre-incubation of the bacteria with N-linked glycans released from human tear proteins inhibiting the adhesion of the ocular P. aeruginosa strains to immobilised tear proteins; 4) inhibition by the N-glycans from lactoferrin of the ability of an ocular strain of P. aeruginosa to invade corneal epithelial cells; 5) removal of terminal sialic acid and fucose moieties from the tear glycoproteins with alpha2-3,6,8 neuraminidase (sialidase) and alpha1-2,3,4 fucosidase resulting in a reduction in binding of the UTI P. aeruginosa isolate, but not the adhesion of the ocular cytotoxic (6206) or invasive (6294) isolates. Glycosidase activity was validated by mass spectrometry. In all cases, the magnitude of inhibition of bacterial adhesion by the N-glycans was consistently greater for the cytotoxic ocular strain than for the invasive ocular strain. Ocular P. aeruginosa isolates seems to exhibit different adhesion mechanism than previously known PAI and PAII lectin adhesion. The work may contribute towards the development of glycan-focused therapies to prevent P. aeruginosa infection of the eye. PMID- 26851488 TI - Interaction of new kinase inhibitors cabozantinib and tofacitinib with human serum alpha-1 acid glycoprotein. A comprehensive spectroscopic and molecular Docking approach. AB - In the current study we have investigated the interaction of newly approved kinase inhibitors namely Cabozantinib (CBZ) and Tofacitinib (TFB) with human Alpha-1 acid glycoprotein (AAG) under simulated physiological conditions using fluorescence quenching measurements, circular dichroism, dynamic light scattering and molecular docking methods. CBZ and TFB binds to AAG with significant affinity and the calculated binding constant for the drugs lie in the order of 10(4). With the increase in temperature the binding constant values decreased for both CBZ and TFB. The fluorescence resonance energy transfer (FRET) from AAG to CBZ and TFB suggested the fluorescence intensity of AAG was quenched by the two studied drugs via the formation of a non-fluorescent complex in the static manner. The molecular distance r value calculated from FRET is around 2 nm for both drugs, fluorescence spectroscopy data was employed for the study of thermodynamic parameters, standard Gibbs free energy change at 300 K was calculated as -5.234 kcal mol(-1) for CBZ-AAG interaction and -6.237 kcal mol(-1) for TFB-AAG interaction, standard enthalpy change and standard entropy change for CBZ-AAG interaction are -9.553 kcal mol(-1) and -14.618 cal mol(-1) K(-1) respectively while for AAG-TFB interaction, standard enthalpy and standard entropy change was calculated as 4.019 kcal mol(-1) and 7.206 cal mol(-1) K(-1) respectively. Protein binding of the two drugs caused the tertiary structure alterations. Dynamic light scattering measurements demonstrated the reduction in the hydrodynamic radii of the protein. Furthermore molecular docking results suggested the Hydrophobic interaction and hydrogen bonding were the interactive forces in the binding process of CBZ to AAG while in case of TFB only hydrophobic interactions were found to be involved, overlap of the binding site for two studied drugs on the AAG molecule was revealed by docking results. PMID- 26851489 TI - Spirolactone and spirothiolactone rhodamine-pyrene probes for detection of Hg2+ with different sensing properties and its application in living cells. AB - Two new rhodamine B-based fluorescent probes PyRbS and PyRbO containing pyrene moiety were designed and synthesized. Both of the probes showed colorimetric and fluorometric sensing abilities for Hg(2+) with high selectivity over other metal ions. The binding analysis using Job's plot suggested 1:1 stoichiometry for the complexes formed for Hg(2+). Compared with PyRbO, the PyRbS showed higher selectivity and sensitivity due to the thiophilic property of Hg(2+) ion. The PyRbS exhibited the linear fluorescence quenching to Hg(2+) in the range of 0.3 to 4.8 MUM (lambda(ex)=365 nm) and 0.3 to 5.4 MUM (lambda(ex)=515 nm), and the detection limit was 0.72 MUM. Moreover, ratiometric changes of PyRbS with Hg(2+) in absorption spectrum were observed, which could not be obtained in the combination of PyRbO with Hg(2+). In addition, the methyl thiazolyl tetrazolium (MTT) assay demonstrated that RbPyS had low cytotoxicity and was successfully used to monitor intracellular Hg(2+) levels in living cells. PMID- 26851490 TI - Stability-indicating methods for the analysis of ciprofloxacin in the presence of its acid induced degradation product: A comparative study. AB - Four rapid, simple, accurate and precise spectrophotometric methods were used for the determination of ciprofloxacin in the presence of its acidic degradation product. The methods under study are ratio derivative, ratio difference, mean centering and dual wavelength. All the methods were validated according to the ICH guidelines and the obtained accuracy, precision and repeatability were found to be within the acceptable limits. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard addition technique. So, they can be used for the routine analysis of ciprofloxacin in quality-control laboratories. PMID- 26851492 TI - SMFM 2016: Meeting highlights-Saturday (Podcast). PMID- 26851491 TI - Dasatinib inhibits HIV-1 replication through the interference of SAMHD1 phosphorylation in CD4+ T cells. AB - Massive activation of infected CD4+ T cells during acute HIV-1 infection leads to reservoir seeding and T-cell destruction. During T-cell activation, the antiviral effect of the innate factor SAMHD1 is neutralized through phosphorylation at T592, allowing HIV-1 infection. Dasatinib, a tyrosine kinase inhibitor currently used for treating chronic myeloid leukemia, has been described to control HIV-1 replication through its negative effect on T-cell proliferation and viral entry. We demonstrate that Dasatinib can actually interfere with SAMHD1 phosphorylation in human peripheral blood lymphocytes, preserving its antiviral activity against HIV-1. Dasatinib prevented SAMHD1 phosphorylation in vitro and ex vivo, impairing HIV-1 reverse transcription and proviral integration. This was the major mechanism of action because the presence of Vpx, which degrades SAMHD1, in HIV-1 virions impeded the inhibitory effect of Dasatinib on HIV-1 replication. In fact, infection with VSV-pseudotyped HIV-1 virions and fusion of BlaM-Vpr-containing HIV-1 viruses with activated PBMCs in the presence of Dasatinib suggested that Dasatinib was not acting at fusion level. Finally, PBMCs from patients on chronic treatment with Dasatinib showed a lower level of SAMHD1 phosphorylation in response to activating stimuli and low susceptibility to HIV-1 infection ex vivo. Consequently, Dasatinib is a compound currently used in clinic that preserves the antiviral function of SAMHD1. Using Dasatinib as adjuvant of antiretroviral therapy during early primary HIV-1 infection would contribute to reduce viral replication and spread, prevent reservoir seeding, and preserve CD4 counts and CTL responses. These events would create a more favorable virologic and immunologic environment for future interventional studies aiming at HIV-1 eradication. PMID- 26851493 TI - Self-regulation strategies may enhance the acute effect of exercise on smoking delay. AB - The present study examined the acute effect of a moderate intensity aerobic exercise session combined with self-regulation on smoking delay in physically inactive smokers. Participants were 11 adults (5 males and 6 females) that completed three experimental conditions: control, exercise, and exercise using self-regulation strategies (SR). Following the experimental treatment smoking for the two exercise conditions delayed significantly more than for the control condition; in addition exercise SR delayed smoking marginally more that the plain exercise condition. Findings supported previous research that acute exercise reduces cravings to smoke, and suggests that the use of self-regulation strategies may strengthen exercise for smoking cessation interventions. PMID- 26851494 TI - Ecological momentary assessment versus standard assessment instruments for measuring mindfulness, depressed mood, and anxiety among older adults. AB - As mobile data capture tools for patient-reported outcomes proliferate in clinical research, a key dimension of measure performance is sensitivity to change. This study compared performance of patient-reported measures of mindfulness, depression, and anxiety symptoms using traditional paper-and-pencil forms versus real-time, ambulatory measurement of symptoms via ecological momentary assessment (EMA). Sixty-seven emotionally distressed older adults completed paper-and-pencil measures of mindfulness, depression, and anxiety along with two weeks of identical items reported during ambulatory monitoring via EMA before and after participation in a randomized trial of Mindfulness-Based Stress Reduction (MBSR) or a health education intervention. We calculated effect sizes for these measures across both measurement approaches and estimated the Number Needed-to-Treat (NNT) in both measurement conditions. Study outcomes greatly differed depending on which measurement method was used. When EMA was used to measure clinical symptoms, older adults who participated in the MBSR intervention had significantly higher mindfulness and significantly lower depression and anxiety than participants in the health education intervention at post-treatment. However, these significant changes in symptoms were not found when outcomes were measured with paper-and-pencil measures. The NNT for mindfulness and depression measures administered through EMA were approximately 25-50% lower than NNTs derived from paper-and-pencil administration. Sensitivity to change in anxiety was similar across administration modes. In conclusion, EMA measures of depression and mindfulness substantially outperformed paper-and-pencil measures with the same items. The additional resources associated with EMA in clinical trials would seem to be offset by its greater sensitivity to detect change in key outcome variables. PMID- 26851495 TI - The Influence of Comorbidity and the Simplified Comorbidity Score on Overall Survival in Non-Small Cell Lung Cancer-A Prospective Cohort Study. AB - INTRODUCTION: We addressed the uncertainty of comorbidity as a prognosticator by evaluating comorbidity and the Simplified Comorbidity Score (SCS) as predictors of overall survival in non-small cell lung cancer (NSCLC). METHODS: A prospective study included patients in whom NSCLC was diagnosed at an Australian cancer hospital between 2012 and 2014. Patients were assessed for SCS at recruitment and followed up every 3 months until death. RESULTS: The cohort included 633 patients; their median age was 67 years (range 28-93), 63% were male, and 86% were ever-smokers. The median SCS at enrolment was 8 (range 0-19); 20% had an SCS higher than 9, and 11% had an SCS of 0. An SCS higher than 9 was associated with male sex, age older than 75 years, an Eastern Cooperative Oncology Group performance status of 2 or higher, and fewer cancer treatments. The 1-year overall survival rate was 62% (95% confidence interval: 58-66). In multivariate analysis, the strongest associations with mortality were metastatic disease (hazard ratio [HR] = 2.8, p < 0.01), Eastern Cooperative Oncology Group performance status of 2 or higher (HR = 2.0, p < 0.01), male sex (HR = 1.6, p < 0.01), more than 10% weight loss at diagnosis (HR = 1.5, p < 0.01), and age older than 75 years (HR = 1.5, p = 0.01). An SCS higher than 9 was not associated with overall survival (HR = 1.0, p = 0.8), and the effect of continuous SCS (HR = 1.1, p < 0.01) was explained by smoking status. CONCLUSIONS: In this cohort of patients with NSCLC the SCS was not a clinically significant predictor of overall survival over and above basic patient and disease factors. PMID- 26851496 TI - Incidence of Lung Adenocarcinoma Biomarker in a Caribbean and African Caribbean Population. AB - INTRODUCTION: Lung cancer is the leading cause of cancer deaths in the United States and worldwide. Biomarker testing is critical to personalized therapy in lung adenocarcinoma and has been extensively investigated in whites and Asians. However, little information addresses the underlying genetic changes among Caribbean and African Caribbean patients. In this study, we identified targetable biomarkers in Caribbean patients with lung adenocarcinoma. METHODS: DNA extracted from lung adenocarcinoma specimens collected from 157 patients in whom primary lung adenocarcinoma was diagnosed from 2013 to 2015 in the University Hospital of Martinique was tested for mutation of the epidermal growth factor receptor gene (EGFR), Kirsten rat sarcoma viral oncogene homolog gene (KRAS), B-Raf proto oncogene, serine/threonine kinase gene (BRAF), phosphatidylinositol-4,5 bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), ROS proto-oncogene 1, receptor tyrosine kinase gene (ROS), and MMNG HOS Transforming gene (MET). Clinical characteristics of our patients have been retrospectively gathered and correlated with mutational status. RESULTS: Mutations in EGFR were identified in 57 cases (36%). Women accounted for 68% of patients with mutations versus 38% of those without mutations (p < 0.001). Eighteen percent of patients with mutations were smokers versus 62% of patients without mutations (p < 0.001). Sex, smoking habit, and age were significantly associated with differences in mutational status in univariate analysis, and the difference remained statistically significant in multivariate analysis (p = 0.0411, p = 0.001, and p = 0.0483, respectively). After the analysis was restricted to patients born in the French West Indies, the mutation rates reached 41%. CONCLUSION: Patients in Martinique, and specifically those of African descent, show very high levels of EGFR mutation as opposed to what can be found in mainland France or in African Americans. These findings may be ascribed to low tobacco consumption as well as to genetic factors. Systematic screening in patients of African Caribbean origin should be prescribed. PMID- 26851497 TI - How widespread is preparation for oxidative stress in the animal kingdom? PMID- 26851498 TI - Heavy metals in agricultural soils of the European Union with implications for food safety. AB - Soil plays a central role in food safety as it determines the possible composition of food and feed at the root of the food chain. However, the quality of soil resources as defined by their potential impact on human health by propagation of harmful elements through the food chain has been poorly studied in Europe due to the lack of data of adequate detail and reliability. The European Union's first harmonized topsoil sampling and coherent analytical procedure produced trace element measurements from approximately 22,000 locations. This unique collection of information enables a reliable overview of the concentration of heavy metals, also referred to as metal(loid)s including As, Cd, Cr, Cu, Hg, Pb, Zn, Sb. Co, and Ni. In this article we propose that in some cases (e.g. Hg and Cd) the high concentrations of soil heavy metal attributed to human activity can be detected at a regional level. While the immense majority of European agricultural land can be considered adequately safe for food production, an estimated 6.24% or 137,000km(2) needs local assessment and eventual remediation action. PMID- 26851499 TI - A comprehensive analysis on Symplocos racemosa Roxb.: Traditional uses, botany, phytochemistry and pharmacological activities. AB - ETHNOPHARMACOLOGICAL RELEVANCE: Symplocos racemosa Roxb. belongs to a unigeneric family Symplocaceae, known as lodhra in Sanskrit; is a small evergreen tree, found throughout the tropical and sub-tropical countries. Ethnobotanical literature indicates use of S. racemosa in treatment of eye disease, skin diseases, ear diseases, liver and bowel complaints, tumors, uterine disorders, spongy and bleeding gums, asthma, fever, snake-bite, gonorrhea and arthritis. The main aim of this review is to provide detailed phytopharmacological profile on S. racemosa in support with the traditional practices and ethnomedicinal uses. MATERIALS AND METHODS: All relevant worldwide accepted databases have been searched for the name "S. racemosa" along with other literature from Indian Classical texts and Pharmacopoeias. The accessible literatures available on S. racemosa, were collected through electronic search on Pub med, Scopus, Science direct and traditional reports. RESULTS: S. racemosa is important Indian traditional drug used in many Ayurvedic and herbal formulations for treatment of liver as well as uterine disorders and leucorrhea. Majority of phytopharmacological reports are on stem bark of the plant which include anti cancer, hepatoprotective, anti-oxidant, anti-androgenic effect, anti inflammatory, wound healing activity and anti-diabetic effects. Phytochemical studies indicated presence of many phenolic glycosides like symplocoside, triterpenoids like betulinic acid, acetyloleanolic acid and oleanolic acid and flavonoids like quercetin which might have contributed to the observed protective effects. CONCLUSION: Many ethnobotanical claims have been confirmed through systematic in-vitro and in-vivo pharmacological studies on different extracts of stem bark and isolated constituents. However, systematic studies on the bio markers are desirable to establish mode of action and to validate the traditional claim in clinical practice after proper safety assessment. The conservation data of genus Symplocos showed risk of extinction due to restricted distribution in the wild hence systematic techniques should be developed for the maintenance of this plant. PMID- 26851500 TI - High-fructose intake as risk factor for neurodegeneration: Key role for carboxy methyllysine accumulation in mice hippocampal neurons. AB - Several studies indicate the involvement of advanced glycation end-products (AGEs) in neurodegenerative diseases. Moreover, the rising consumption of fructose in industrialized countries has been related to cognitive impairment, but the impact of fructose-derived AGEs on hippocampus has never been investigated. The present study aimed to evaluate in the hippocampus of C57Bl/6 mice fed a standard (SD) or a 60% fructose (HFRT) diet for 12 weeks the production of the most studied AGEs, carboxy methyllysine (CML), focusing on the role of the glutathione-dependent enzyme glyoxalase (Glo-1), the main AGEs detoxifying system, in relation to early signs of neuronal impairment. HFRT diet evoked CML accumulation in the cell body of pyramidal neurons, followed by RAGE/NFkB signaling activation. A widespread reactive gliosis and altered mitochondrial respiratory complexes activity have been evidenced in HFRT hippocampi, paralleled by oxidative stress increase due to impaired activity of Nrf2 signaling. In addition, a translocation of Glo-1 from axons toward cell body of pyramidal neurons has been observed in HFRT mice, in relation to CML accumulation. Despite increased expression of dimeric Glo-1, its enzymatic activity was not upregulated in HFRT hippocampi, due to reduced glutathione availability, thus failing to prevent CML accumulation. The prevention of CML production by administration of the specific inhibitor pyridoxamine was able to prevent all the fructose-induced hippocampal alterations. In conclusion, a high fructose consumption, through CML accumulation and Glo-1 impairment, induces in the hippocampus the same molecular and metabolic alterations observed in early phases of neurodegenerative diseases, and can thus represent a risk factor for their onset. PMID- 26851501 TI - Specific promoter deacetylation of histone H3 is conserved across mouse models of Huntington's disease in the absence of bulk changes. AB - Defective epigenetic regulation has been postulated as a possible cause for the extensive and premature transcriptional dysregulation observed in experimental models of Huntington's disease (HD). In this study, we extended our observations in the N171-82Q mouse strain relating to the limited impact of polyQ pathology on the global histone acetylation to other animal and cellular models of HD, namely the R6/1 and YAC128 strains, striatal-electroporated mice, primary neuronal cultures and stably transfected PC12 cells. In the absence of bulk chromatin changes, we nonetheless documented histone deacetylation events at the transcription start sites (TSS) of genes relevant to neuronal functions (e.g., Rin1, Plk5, Igfbp5, Eomes, and Fos). In some instances, these local deficits were associated with an increased susceptibility to transcriptional dysregulation (e.g., Camk1g and Rasl11b) and the defective trimethylation of histone H3 at lysine 4 (H3K4me3), another covalent modification of histone tails that is related to active transcription and is also altered in HD. Overall, this study provides further insight into the nature and extent of epigenetic dysregulation in HD pathology. PMID- 26851502 TI - Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry. AB - Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early-use critical period. PMID- 26851504 TI - On prilled Nanotubes-in-Microgel Oral Systems for protein delivery. AB - Newly discovered active macromolecules are highly promising for therapy, but poor bioavailability hinders their oral use. Microencapsulation approaches, such as protein prilling into microspheres, may enable protection from gastrointestinal (GI) enzymatic degradation. This would increase bioavailability mainly for local delivery to GI lumen or mucosa. This work's purpose was to design a novel architecture, namely a Nanotubes-in-Microgel Oral System, by prilling for protein delivery. Halloysite nanotubes (HNT) were selected as orally acceptable clay particles and their lumen was enlarged by alkaline etching. This chemical modification increased the luminal volume to a mean of 216.3 MUL g(-1) (+40.8%). After loading albumin as model drug, the HNT were entrapped in microgels by prilling. The formation of Nanoparticles-in-Microsphere Oral System (NiMOS) yielded entrapment efficiencies up to 63.2%. NiMOS shape was spherical to toroidal, with a diameter smaller than 320 MUm. Release profiles depended largely on the employed system and HNT type. Protein stability was determined throughout prilling and after in vitro enzymatic degradation. Prilling did not harm protein structure, and NiMOS demonstrated higher enzymatic protection than pure nanotubes or microgels, since up to 82% of BSA remained unscathed after in vitro digestion. Therefore, prilled NiMOS was shown to be a promising and flexible multi compartment system for oral (local) macromolecular delivery. PMID- 26851505 TI - 5-Substituted 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2)H-pyrazolo[4,3 d]pyrimidines with anti-proliferative activity as potent and selective inhibitors of cyclin-dependent kinases. AB - A series of 5-substituted 3-isopropyl-7-[4-(2-pyridyl)benzyl]amino-1(2)H pyrazolo[4,3-d]pyrimidine derivatives was synthesized and evaluated for their cyclin-dependent kinase (CDK) inhibition activity. The most potent compounds contained various hydroxyalkylamines at the 5 position and possessed low nanomolar IC50 values for CDK2 and CDK5. Preliminary profiling of one of the most active compounds on a panel of 50 protein kinases revealed its high selectivity for CDKs. The compounds arrested cells in S and G2/M phases, and induced apoptosis in various cancer cell lines. Significant dephosphorylation of the C terminus of RNA polymerase II and focal adhesion kinase (FAK), well-established substrates of CDKs, has been found in treated cells. Cleavage of PARP-1, down regulation of Mcl-1 and activation of caspases correlated well with CDK inhibition and confirmed apoptosis as the primary type of cell death induced in cancer cells treated with the compounds in vitro. A comparison of known purine based CDK inhibitor CR8 with its pyrazolo[4,3-d]pyrimidine bioisosteres confirmed that the novel compounds are more potent in cellular assays than purines. Therefore, pyrazolo[4,3-d]pyrimidine may emerge as a novel scaffold in medicinal chemistry and as a source of potent CDK inhibitors. PMID- 26851503 TI - The Janus kinase inhibitor ruxolitinib reduces HIV replication in human macrophages and ameliorates HIV encephalitis in a murine model. AB - A hallmark of persistent HIV-1 infection in the central nervous system is increased activation of mononuclear phagocytes and surrounding astrogliosis, conferring persistent HIV-induced inflammation. This inflammation is believed to result in neuronal dysfunction and the clinical manifestations of HIV-associated neurocognitive disorders (HAND). The Jak/STAT pathway is activated in macrophages/myeloid cells upon HIV-1 infection, modulating many pro-inflammatory pathways that result in HAND, thereby representing an attractive cellular target. Thus, the impact of ruxolitinib, a Janus Kinase (Jak) 1/2 inhibitor that is FDA approved for myelofibrosis and polycythemia vera, was assessed for its potential to inhibit HIV-1 replication in macrophages and HIV-induced activation in monocytes/macrophages in culture. In addition, a murine model of HIV encephalitis (HIVE) was used to assess the impact of ruxolitinib on histopathological features of HIVE, brain viral load, as well as its ability to penetrate the blood-brain barrier (BBB). Ruxolitinib was found to inhibit HIV-1 replication in macrophages, HIV-induced activation of monocytes (CD14/CD16) and macrophages (HLA-DR, CCR5, and CD163) without apparent toxicity. In vivo, systemically administered ruxolitinib was detected in the brain during HIVE in SCID mice and markedly inhibited astrogliosis. Together, these data indicate that ruxolitinib reduces HIV-induced activation and infiltration of monocytes/macrophages in vitro, reduces the replication of HIV in vitro, penetrates the BBB when systemically administered in mice and reduces astrogliosis in the brains of mice with HIVE. These data suggest that ruxolitinib will be useful as a novel therapeutic to treat humans with HAND. PMID- 26851507 TI - The safety of the use of bisphenol A in medical devices. PMID- 26851506 TI - Differential analyses of major allergen proteins in wild-type rice and rice producing a fragment of anti-rotavirus antibody. AB - To develop oral antibody therapy against rotavirus infection, we previously produced a recombinant fragment of llama heavy-chain antibody to rotavirus (ARP1) in rice seeds (MucoRice-ARP1). We intend to use a purification-free rice powder for clinical application but needed to check whether MucoRice-ARP1 had increased levels of known allergen proteins. For this purpose, we used two-dimensional fluorescence difference gel electrophoresis to compare the allergen protein levels in MucoRice-ARP1 and wild-type rice. We detected no notable differences, except in the levels of alpha-amylase/trypsin inhibitor-like family proteins. Because by this approach we could not completely separate ARP1 from the proteins of this family, we confirmed the absence of changes in the levels of these allergens by using shotgun mass spectrometry as well as immunoblot. By using immunoelectron microscopy, we also showed that RAG2, a member of the alpha amylase/trypsin inhibitor-like protein family, was relocated from protein bodies II to the plasma membrane or cell wall in MucoRice-ARP1 seed. The relocation did not affect the level of RAG2. We demonstrated that most of the known rice allergens were not considerably upregulated by the genetic modification in MucoRice-ARP1. Our data suggest that MucoRice-ARP1 is a potentially safe oral antibody for clinical application. PMID- 26851508 TI - The bottom-up approach to bounding potential low-dose cancer risks from formaldehyde: An update. AB - In 2013, we proposed a novel bottom-up approach to bounding low-dose cancer risks that may result from small exogenous exposures to chemicals that are always present in the body as a result of normal biological processes. The approach utilizes the background cancer risk and the background (endogenous) concentration of a cancer-related exposure biomarker in specific target tissues. After allowing for statistical uncertainty in these two parameters, the ratio of the background risk to background exposure provides a conservative slope factor estimate that can be utilized to bound the added risk that may be associated with incremental exogenous exposures. Our original bottom-up estimates were markedly smaller than those obtained previously by the US Environmental Protection Agency (USEPA) with a conventional top-down approach to modeling nasopharyngeal cancer and leukemia mortality data from a US worker cohort. Herein we provide updated bottom-up estimates of risk for these two cancers that are smaller still, and rely upon more robust estimates of endogenous and exogenous formaldehyde-DNA adducts in monkeys and a more robust estimate of the DNA adduct elimination half-life in rats, both obtained very recently. We also re-examine the worker mortality data used by USEPA in developing its estimate of human leukemia incidence from lifetime exposure to 1 ppm airborne formaldehyde. Finally, we compare a new bottom-up slope estimate of the risk of rat nasal cancer with conventional top down estimates obtained with empirical dose-response modeling of rat nasal cancer bioassay data. PMID- 26851509 TI - Tissue tropism and molecular characterization of a Japanese encephalitis virus strain isolated from pigs in southwest China. AB - Since September 2012, an epidemic has been spreading among swine in a pig farm located in Sichuan province, southwest China, which has resulted in abortion, stillbirth, and fetal mummification. The brains of stillborn pigs were collected and a previously unknown Japanese encephalitis virus (JEV), namely SCYA201201, was isolated. According to the results of agarose gel diffusion precipitation, indirect immunofluorescence analysis, neutralization testing, reverse transcription PCR (RT-PCR) amplification, and physical and chemical testing, the virus was conformed to have the characteristics of JEV. The virus titer in BHK-21 cells was 10(8.47)PFU/ml and the median lethal dose (LD50) to 3-week-old and 7 day-old mice was 1.99 log10 and 1.02 log10 PFU/LD50, respectively. The results of tissue tropism for mice showed that the viral load in the brain was significantly higher than other organs, indicating that the isolate was strongly neurotropic. Additionally, the complete genome sequence of the isolate was determined and compared with other JEV strains. Phylogenetic analysis showed that the isolate belongs to genotype I and may be an imported virus. The isolate had 88.4% nucleotide identity with the Chinese vaccine strain SA14-14-2. However, there were 69 amino acid substitutions compared with the strain SA14-14-2. Some substitutions indicated that SCYA201201 was highly neurovirulent and infective, in accordance with the results of animal testing. PMID- 26851510 TI - GPCRs of adrenal chromaffin cells & catecholamines: The plot thickens. AB - The circulating catecholamines (CAs) epinephrine (Epi) and norepinephrine (NE) derive from two major sources in the whole organism: the sympathetic nerve endings, which release NE on effector organs, and the chromaffin cells of the adrenal medulla, which are cells that synthesize, store and release Epi (mainly) and NE. All of the Epi in the body and a significant amount of circulating NE derive from the adrenal medulla. The secretion of CAs from adrenal chromaffin cells is regulated in a complex way by a variety of membrane receptors, the vast majority of which are G protein-coupled receptors (GPCRs), including adrenergic receptors (ARs), which act as "presynaptic autoreceptors" in this regard. There is a plethora of CA-secretagogue signals acting on these receptors but some of them, most notably the alpha2ARs, inhibit CA secretion. Over the past few years, however, a few new proteins present in chromaffin cells have been uncovered to participate in CA secretion regulation. Most prominent among these are GRK2 and beta-arrestin1, which are known to interact with GPCRs regulating receptor signaling and function. The present review will discuss the molecular and signaling mechanisms by which adrenal chromaffin cell-residing GPCRs and their regulatory proteins modulate CA synthesis and secretion. Particular emphasis will be given to the newly discovered roles of GRK2 and beta-arrestins in these processes and particular points of focus for future research will be highlighted, as well. PMID- 26851511 TI - MiR-18b suppresses high-glucose-induced proliferation in HRECs by targeting IGF 1/IGF1R signaling pathways. AB - MicroRNAs (miRNAs) are important for the proliferation of endothelial cells and have been shown to be involved in diabetic retinopathy (DR). In previous study, we found that miRNAs might play a critical role in hyperglycemia-induced endothelial cell proliferation based on miRNA expression profiling. Here, the roles of microRNA-18b (miR-18b) in the proliferation of human retinal endothelial cells (HRECs) were investigated in an in vitro model of HRECs grown in high glucose. We identified that levels of miR-18b were decreased in high-glucose induced HRECs, compared with those in cells incubated in normal glucose. However, the reduction of miR-18b up-regulated vascular endothelial growth factor (VEGF) secretion and promoted effects on in vitro proliferation of HRECs. Mechanistically, insulin growth factor-1 (IGF-1) was identified as a target of miR-18b. IGF-1 simulation could antagonize the effect induced by miR-18b up regulation, promoting cell proliferation and increasing VEGF production. In contrast, the opposite results were observed with silencing IGF-1, which was consistent with the effects of miR-18b overexpression. MiR-18b exerted its function on VEGF synthesis and cell proliferation by suppressing the IGF 1/insulin growth factor-1 receptor (IGF1R) pathway, consequently inhibiting the downstream phosphorylation of Akt, MEK, and ERK. Hence, this may provide a new insight into understanding the mechanism of DR pathogenesis, as well as a potential therapeutic target for proliferative DR. PMID- 26851512 TI - TLR-7 agonist attenuates airway reactivity and inflammation through Nrf2-mediated antioxidant protection in a murine model of allergic asthma. AB - Toll-like receptors (TLRs) through innate immune system recognize pathogen associated molecular patterns and play an important role in host defense against bacteria, fungi and viruses. TLR-7 is responsible for sensing single stranded nucleic acids of viruses but its activation has been shown to be protective in mouse models of asthma. The NADPH oxidase (NOX) enzymes family mainly produces reactive oxygen species (ROS) in the lung and is involved in regulation of airway inflammation in response to TLRs activation. However, NOX-4 mediated signaling in response to TLR-7 activation in a mouse model of allergic asthma has not been explored previously. Therefore, this study investigated the role TLR-7 activation and downstream oxidant-antioxidant signaling in a murine model of asthma. Mice were sensitized with ovalbumin (OVA) intraperitoneally and treated with TLR-7 agonist, resiquimod (RSQ) intranasally before each OVA challenge from days 14 to 16. Mice were then assessed for airway reactivity, inflammation, and NOX-4 and nuclear factor E2-related factor 2 (Nrf2) related signaling [inducible nitric oxide synthase (iNOS), nitrotyrosine, lipid peroxides and copper/zinc superoxide dismutase (Cu/Zn SOD)]. Treatment with RSQ reduced allergen induced airway reactivity and inflammation. This was paralleled by a decrease in ROS which was due to induction of Nrf2 and Cu/Zn SOD in RSQ treated group. Inhibition of MyD88 reversed RSQ-mediated protective effects on airway reactivity/inflammation due to reduction in Nrf2 signaling. SOD inhibition produced effects similar to MyD88 inhibition. The current study suggests that TLR-7 agonist is beneficial and may be developed into a therapeutic option in allergic asthma. PMID- 26851513 TI - Enzymatic breakage of dimethylsulfoniopropionate-a signature molecule for life at sea. AB - Largely using gene-based evidence, the last few years have seen real insights on the diverse ways in which different microbes break down dimethylsulfoniopropionate, an abundant anti-stress molecule that is made by marine algae, some corals and a few angiosperms. Here, we review more recent advances in which in vitro biochemical tools-including structural determinations have shed new light on how the corresponding enzymes act on DMSP. These have revealed how enzymes in very different polypeptide families can act on this substrate, often by novel ways, and with broader implications that extend from enzymatic mechanisms to microbial ecology. PMID- 26851514 TI - Harvesting the biosynthetic machineries that cultivate a variety of indispensable plant natural products. AB - Plants are a sustainable resource for valuable natural chemicals best illustrated by large-scale farming centered on specific products. Here, we review recent discoveries of plant metabolic pathways producing natural products with unconventional biomolecular structures. Prenylation of polyketides by aromatic prenyltransferases (aPTases) ties together two of the major groups of plant specialized chemicals, terpenoids and polyketides, providing a core modification leading to new bioactivities and downstream metabolic processing. Moreover, PTases that biosynthesize Z-terpenoid precursors for small molecules such as lycosantalene have recently been found in the tomato family. Gaps in our understanding of how economically important compounds such as cannabinoids are produced are being identified using next-generation 'omics' to rapidly advance biochemical breakthroughs at an unprecedented rate. For instance, olivetolic acid cyclase, a polyketide synthase (PKS) co-factor from Cannabis sativa, directs the proper cyclization of a polyketide intermediate. Elucidations of spatial and temporal arrangements of biosynthetic enzymes into metabolons, such as those used to control the efficient production of natural polymers such as rubber and defensive small molecules such as linamarin and lotaustralin, provide blueprints for engineering streamlined production of plant products. PMID- 26851515 TI - Acanthamoeba and Fusarium interactions: A possible problem in keratitis. AB - The incidence of Acanthamoeba and Fusarium species has increased in contact lens related infectious keratitis. They share several environments and cases of co infection have been reported. The interaction between the amoebae and other microorganisms may result in significant changes for both, like increased virulence in mammalian hosts. In this study, we evaluated the interaction of three Acanthamoeba castellanii strains with Fusarium conidia and the possible implications on keratitis. F. conidia were internalized by A. castellanii strains and were able to germinate inside the amoebae. The co-culture with the live amoebae, as well as the amoebal culture supernatant and lysate, increased the fungal growth significantly. Moreover, live F. solani and its culture supernatant enhanced the survival of amoebae, but in a different way in each amoebal strain. The encystment of the A. castellanii strain re-isolated from rat lung was increased by the fungus. These results show that A. castellanii and F. solani interaction may have an important influence on survival of both, and specially indicate a possible effect on virulence characteristics of these microorganisms. These data suggest that the A. castellanii-F. solani interaction may cause severe impacts on keratitis. PMID- 26851516 TI - The core of hepatitis C virus pathogenesis. AB - Capsid proteins form protective shells around viral genomes and mediate viral entry. However, many capsid proteins have additional and important roles for virus infection and in modulating cellular response to infection, with important consequences on pathogenesis. Infection by the Hepatitis C virus (HCV) can lead to liver steatosis, cirrhosis, and hepatocellular carcinoma. Herein, we focus on the role in pathogenesis of Core, the capsid protein of the HCV. PMID- 26851517 TI - An international survey of medical licensing requirements for immigrating physicians, focusing on communication evaluation. AB - OBJECTIVE: To identify current entry requirements set by international medical licensing bodies for immigrating physicians, focusing on postgraduate level communication skills, clinical and technical skill assessments. METHODS: A standardised, author developed survey was administered to a selection of national, state and provincial licensing institutions across 6 continents. Representative institutions were selected from the most populated regions of each continent. Surveys were administered by email and telephone. The information was also searched by website review. Website information alone was used if no response was received by the targeted institution after 2 phone/2 email attempts. Statistical analysis of the non-parametric data was conducted using SPSS (v.21). RESULTS: Thirty-seven licensing bodies were contacted from 30 countries; verifiable information was available for 29; twenty-six responded to the communication inquiry. Sixty five 65.4% (n=17) surveyed communication skills, 100% involved language proficiency testing; 11.5% tested other forms of communication skills. For clinical and technical skills, 86.2% (n=25) assessed candidates by credential review, 72.4% (n=21) required both credential review and exam and 62.1% (n=18) used country-specific examination. A mentorship period were required by 37.9% (n=11), ranging from 3 months to 1 year. Only 2 countries identified examinations for recertification. No technical/clinical skills nor communication skill evaluation (beyond language proficiency) are routinely assessed at the postgraduate level. CONCLUSIONS: International assessments of migrating physicians are heterogeneous. Communication skills, beyond language proficiency, are not routinely assessed in foreign trained physicians seeking entry. The majority of clinical and technical skills are assessed by credential review only. This study highlights the lack of standardisation of assessment internationally and the need for steps toward a global agreement on training schemes and summative assessment. PMID- 26851518 TI - Generalized Lymphadenopathy of Prostate Adenocarcinoma Origin. A Case Series. AB - Generalized lymphadenopathy is a rare manifestation of metastatic prostate cancer. We report on 2 cases of prostate adenocarcinoma, which clinically manifested as generalized lymphadenopathy. The origin of the primary tumor was confirmed by transrectal ultrasound-guided prostate biopsy. We underline the fact that a suspicion of prostate cancer in men with adenocarcinoma of undetermined origin is important for an adequate and complete diagnostic and therapeutic approach. PMID- 26851520 TI - Homogeneous plate based antibody internalization assay using pH sensor fluorescent dye. AB - Receptor-mediated antibody internalization is a key mechanism underlying several anti-cancer antibody therapeutics. Delivering highly toxic drugs to cancer cells, as in the case of antibody drug conjugates (ADCs), efficient removal of surface receptors from cancer cells and changing the pharmacokinetics profile of the antibody drugs are some of key ways that internalization impacts the therapeutic efficacy of the antibodies. Over the years, several techniques have been used to study antibody internalization including radiolabels, fluorescent microscopy, flow cytometry and cellular toxicity assays. While these methods allow analysis of internalization, they have limitations including a multistep process and limited throughput and are generally endpoint assays. Here, we present a new homogeneous method that enables time and concentration dependent measurements of antibody internalization. The method uses a new hydrophilic and bright pH sensor dye (pHAb dye), which is not fluorescent at neutral pH but becomes highly fluorescent at acidic pH. For receptor mediated antibody internalization studies, antibodies against receptors are conjugated with the pHAb dye and incubated with the cells expressing the receptors. Upon binding to the receptor, the dyes conjugated to the antibody are not fluorescent because of the neutral pH of the media, but upon internalization and trafficking into endosomal and lysosomal vesicles the pH drops and dyes become fluorescent. The enabling attributes of the pHAb dyes are the hydrophilic nature to minimize antibody aggregation and bright fluorescence at acidic pH which allows development of simple plate based assays using a fluorescent reader. Using two different therapeutic antibodies- Trastuzumab (anti-HER2) and Cetuximab (anti-EGFR)--we show labeling with pHAb dye using amine and thiol chemistries and impact of chemistry and dye to antibody ration on internalization. We finally present two new approaches using the pHAb dye, which will be beneficial for screening a large number of antibody samples during early monoclonal development phase. PMID- 26851519 TI - pMINERVA: A donor-acceptor system for the in vivo recombineering of scFv into IgG molecules. AB - Phage display is the most widely used method for selecting binding molecules from recombinant antibody libraries. However, validation of the phage antibodies often requires early production of the cognate full-length immunoglobulin G (IgG). The conversion of phage library outputs to a full immunoglobulin via standard subcloning is time-consuming and limits the number of clones that can be evaluated. We have developed a novel system to convert scFvs from a phage display vector directly into IgGs without any in vitro subcloning steps. This new vector system, named pMINERVA, makes clever use of site-specific bacteriophage integrases that are expressed in Escherichia coli and intron splicing that occurs within mammalian cells. Using this system, a phage display vector contains both bacterial and mammalian regulatory regions that support antibody expression in E. coli and mammalian cells. A single-chain variable fragment (scFv) antibody is expressed on the surface of bacteriophage M13 as a genetic fusion to the gpIII coat protein. The scFv is converted to an IgG that can be expressed in mammalian cells by transducing a second E. coli strain. In that strain, the phiC31 recombinase fuses the heavy chain constant domain from an acceptor plasmid to the heavy chain variable domain and introduces controlling elements upstream of the light chain variable domain. Splicing in mammalian cells removes a synthetic intron containing the M13 gpIII gene to produce the fusion of the light chain variable domain to the constant domain. We show that phage displaying a scFv and recombinant IgGs generated using this system are expressed at wild-type levels and retain normal function. Use of the pMINERVA completely eliminates the labor intensive subcloning and DNA sequence confirmation steps currently needed to convert a scFv into a functional IgG Ab. PMID- 26851521 TI - Simple and reliable genotyping protocol for mouse Prkdc(SCID) mutation. AB - Mutant mouse models, genetically-engineered or spontaneous-mutations, serve as valuable tools for biomedical research. Genotyping of mutant mice is a critical requirement for maintaining the colony, to breed with other mutants and to match the phenotypic observations. The SCID (Severe Combine Immuno Deficiency) mouse model has been extensively used as a common background-strain in many immunology and transplantation studies. Many different types of assays, including Restriction Fragment Length Polymorphism (RFLP), confronting two primer pairs PCR and end-point methods have been attempted for establishing a genotyping protocol for the SCID mutation. However, the best method that is thought to be reliable is sequencing, which requires additional time and resources to perform on a routine basis. In this report, we describe a novel RFLP assay that is simple and reliable. The method is validated by sequencing analysis, and this novel method can be adapted for routine genotyping of SCID model. PMID- 26851522 TI - Simultaneous detection of five one-carbon metabolites in plasma using stable isotope dilution liquid chromatography tandem mass spectrometry. AB - Disturbance in one-carbon (1-C) cycle occurs due to nutritional deficiencies (vitamin B12/folate) or specific genetic polymorphisms. This leads to altered levels of key 1-C metabolites such as SAM (s-adenosyl methionine), SAH (s adenosyl homocysteine), methionine, homocysteine and MMA (methyl malonic acid). These 1-C metabolites are determinants of cellular methylation potential and epigenetic modifications of DNA which impairs metabolic pathways in several pathological diseases and developmental programming. Though methods were able to measure these analytes only independently, none of the methods detect simultaneously. Therefore we developed a method to measure these five 1-C metabolites in a single run using liquid chromatography tandem mass spectrometry (LC-MS/MS). We used stable isotopes dilution LC-MS/MS to measure the 1-C metabolites in human plasma. Blood samples were collected from pregnant women (n=30) at early gestation in the ongoing, multicentre, prospective PRiDE study. Linearity exhibited across the calibration range for all the analytes with the limit of detection (LOD) of 1.005nmol/l for SAM, 0.081nmol/l for SAH, 0.002MUmol/l for methionine, 0.046MUmol/l for homocysteine and 3.920nmol/l for MMA. The average recovery for SAM was 108%, SAH-110%, methionine-97%, homocysteine-91% and MMA-102%. The inter-assay CV for SAM was 7.3, SAH-5.6%, methionine-3.5%, homocysteine-7.0% and MMA-4.0%. The intra-assay CV for SAM was 8.7%, SAH-4.7%, methionine-5.4%, homocysteine-8.1% and MMA-6.1%. Pregnant women at early gestation with low B12 levels had significantly higher homocysteine, MMA, lower levels of methionine, SAM and SAM:SAH ratio and higher triglycerides. We developed a simple and rapid method to simultaneously quantify 1-C metabolites such as SAM, SAH, methionine, homocysteine and MMA in plasma by stable isotope dilution LC-MS/MS which would be useful to elucidate the epigenetic mechanisms related in the gene-nutrient interactions. PMID- 26851523 TI - Sialic acid-specific affinity chromatography for the separation of erythropoietin glycoforms using serotonin as a ligand. AB - Recombinant human erythropoietin (rhEPO) is an important CHO cell-derived glycoprotein and the degree of sialylation of this hormone is crucial for its in vivo bioactivity. In order to improve the purification process serotonin as a potential affinity ligand was tested for preparative chromatographic separation of rhEPO glycoforms into fractions of different degrees of sialylation. Therefore, two chromatographic matrices were prepared by immobilizing serotonin on CNBr- and NHS-SepharoseTM. First it was shown both matrices bind rhEPO only in its sialylated form. Results indicate that binding is pH independent between pH 3.5 to 8 suggesting it is not only based on electrostatic interactions. Second, after optimal binding conditions were identified, semi-purified rhEPO was loaded onto both matrices and eluted using a stepwise elution gradient of sodium chloride. For comparison same affinity purification experiments were performed using wheat germ agglutinin-coupled agarose, a lectin known for its affinity towards sialylated glycoproteins. To monitor changes in N-glycan fingerprint, eluate fractions were analyzed by multiplexed capillary gel electrophoresis coupled to laser-induced fluorescence (xCGE-LIF). For the serotonin matrices an increasing degree of sialylation was observed from the first to the third elution fraction while purity of rhEPO could be increased at the same time. The late elution fractions of serotonin-coupled CNBr- and NHS-SepharoseTM also showed an overall sialylation degree exceeding that of the starting material. In contrast, for rhEPO bound to wheat germ agglutinin-coupled agarose, no distinct change in the degree of sialylation could be observed after elution. Overall, these encouraging results highlight the potential of serotonin as a chromatographic ligand for the improvement of pharmaceutical purification processes of rhEPO. PMID- 26851524 TI - Somatic mosaicism of the PIK3CA gene identified in a Hungarian girl with macrodactyly and syndactyly. AB - Isolated macrodactyly (OMIM 155500) belongs to a heterogeneous group of overgrowth syndromes. It is a congenital anomaly resulting in enlargement of all tissues localized to the terminal portions of a limb and caused by somatic mutations in the phosphatidylinositol 3-kinase catalytic alpha (PIK3CA, OMIM 171834) gene. Here we report a Hungarian girl with macrodactyly and syndactyly. Genetic screening at hotspots in the PIK3CA gene identified a mosaic mutation (c.1624G > A, p.Glu542Lys) in the affected tissue, but not in the peripheral blood. To date, this somatic mutation has been reported in eight patients affected by different forms of segmental overgrowth syndromes. Detailed analysis of the Hungarian child and previously reported cases suggests high phenotypic diversity associated with the p.Glu542Lys somatic mutation. The identification of the mutation provides a novel therapeutic modality for the affected patients: those who carry somatic mutations in the PIK3CA gene are potential recipients of a novel "repurposing" approach of rapamycin treatment. PMID- 26851525 TI - Seven novel mutations of the SMPD1 gene in four Chinese patients with Niemann Pick disease type A and prenatal diagnosis for four fetuses. AB - BACKGROUND: Niemann-Pick disease type A (NPD-A) is a rare autosomal recessive lysosomal storage disorder caused by acid sphingomyelinase deficiency. Only a few cases have been documented in mainland China, and prenatal diagnosis has not been performed to date. In this study, the clinical and laboratory features of four Chinese patients with early-onset NPD-A were summarized. METHODS: Four patients with NPD-A were the firstborns of non-consanguineous parents from four unrelated Chinese families. Bone marrow analysis, acid sphingomyelinase assay and genetic studies were performed. SMPD1 gene studies on amniocytes were performed for the prenatal diagnosis of four fetuses from three families. RESULTS: Four patients were admitted at the age of 1-10 months due to jaundice, hepatosplenomegaly and psychomotor retardation. Liver histopathological analysis revealed glucolipid accumulation. Massive foamy histiocytes were found in the bone marrow. Acid sphingomyelinase activities of peripheral blood leukocytes were significantly decreased (4.05-21.9 nmol/h/mg protein, normal range 216.1-950.9 nmol/h/mg protein). Seven novel mutations (c.518-519insT, c.562_563insC, c.792Gdel, c.949G>A, c.1487_1499delACCGTGTGTACCA, c.1495T>C and c.1670T>C) of the SMPD1 gene were identified in four patients. Only one fetus had two mutations of the SMPD1 gene of amniocytes. The results suggested that the fetus was affected by NPD-A. The mother chose artificial abortion. The other three fetuses were not affected by NPD-A. No mutation of the SMPD1 gene was detected in the cultured amniocytes from the mothers. Postnatal genetic analysis and normal development of the three infants confirmed the prenatal diagnosis. CONCLUSIONS: Seven novel mutations associated with NPD-A were identified in the Chinese population. Prenatal diagnosis for four fetuses of three families was successfully performed by amniocyte gene analysis. PMID- 26851526 TI - Prevotella brain abscess in a healthy young patient with a patent foramen ovale. AB - Brain abscesses are frequently caused by poly-microbial conditions. Comparatively, brain abscesses caused by Prevotella species are very rare. Right to-left cardiac shunting due to a patent foramen ovale may predispose patients to infection. We report an isolated Prevotella brain abscess that occurred in a healthy, young, male patient with a patent foramen ovale. The patient did not have a clinically obvious odontogenic source of infection, and no other distant extracranial infectious sources were observed. The patient was successfully treated with stereotactic aspiration and antibiotics. PMID- 26851527 TI - Mechanical properties of normal and osteoarthritic human articular cartilage. AB - Isotropic hyperelastic models have been used to determine the material properties of normal human cartilage, but there remains an incomplete understanding of how these properties may be altered by osteoarthritis. The aims of this study were to (1) measure the material constants of normal and osteoarthritic human knee cartilage using isotropic hyperelastic models; (2) determine whether the material constants correlate with histological measures of structure and/or cartilage tissue damage; and (3) quantify the abilities of two common isotropic hyperelastic material models, the neo-Hookean and Yeoh models, to describe articular cartilage contact force, area, and pressure. Small osteochondral specimens of normal and osteoarthritic condition were retrieved from human cadaveric knees and from the knees of patients undergoing total knee arthroplasty and tested in unconfined compression at loading rates and large strains representative of weight-bearing activity. Articular surface contact area and lateral deformation were measured concurrently and specimen-specific finite element models then were used to determine the hyperelastic material constants. Structural parameters were measured using histological techniques while the severity of cartilage damage was quantified using the OARSI grading scale. The hyperelastic material constants correlated significantly with OARSI grade, indicating that the mechanical properties of cartilage for large strains change with tissue damage. The measurements of contact area described anisotropy of the tissue constituting the superficial zone. The Yeoh model described contact force and pressure more accurately than the neo-Hookean model, whereas both models under-predicted contact area and poorly described the anisotropy of cartilage within the superficial zone. These results identify the limits by which isotropic hyperelastic material models may be used to describe cartilage contact variables. This study provides novel data for the mechanical properties of normal and osteoarthritic human articular cartilage and enhances our ability to model this tissue using simple isotropic hyperelastic materials. PMID- 26851528 TI - Molecular modeling of the elastomeric properties of repeating units and building blocks of resilin, a disordered elastic protein. AB - The mechanisms responsible for the properties of disordered elastomeric proteins are not well known. To better understand the relationship between elastomeric behavior and amino acid sequence, we investigated resilin, a disordered rubber like protein, found in specialized regions of the cuticle of insects. Resilin of Drosophila melanogaster contains Gly-rich repetitive motifs comprised of the amino acids, PSSSYGAPGGGNGGR, which confer elastic properties to resilin. The repetitive motifs of insect resilin can be divided into smaller partially conserved building blocks: PSS, SYGAP, GGGN and GGR. Using molecular dynamics (MD) simulations, we studied the relative roles of SYGAP, and its less common variants SYSAP and TYGAP, on the elastomeric properties of resilin. Results showed that SYGAP adopts a bent structure that is one-half to one-third the end to-end length of the other motifs having an equal number of amino acids but containing SYSAP or TYGAP substituted for SYGAP. The bent structure of SYGAP forms due to conformational freedom of glycine, and hydrogen bonding within the motif apparently plays a role in maintaining this conformation. These structural features of SYGAP result in higher extensibility compared to other motifs, which may contribute to elastic properties at the macroscopic level. Overall, the results are consistent with a role for the SYGAP building block in the elastomeric properties of these disordered proteins. What we learned from simulating the repetitive motifs of resilin may be applicable to the biology and mechanics of other elastomeric biomaterials, and may provide us the deeper understanding of their unique properties. PMID- 26851529 TI - Neem leaf glycoprotein promotes dual generation of central and effector memory CD8(+) T cells against sarcoma antigen vaccine to induce protective anti-tumor immunity. AB - We have previously shown that Neem Leaf Glycoprotein (NLGP) mediates sustained tumor protection by activating host immune response. Now we report that adjuvant help from NLGP predominantly generates CD44(+)CD62L(high)CCR7(high) central memory (TCM; in lymph node) and CD44(+)CD62L(low)CCR7(low) effector memory (TEM; in spleen) CD8(+) T cells of Swiss mice after vaccination with sarcoma antigen (SarAg). Generated TCM and TEM participated either to replenish memory cell pool for sustained disease free states or in rapid tumor eradication respectively. TCM generated after SarAg+NLGP vaccination underwent significant proliferation and IL 2 secretion following SarAg re-stimulation. Furthermore, SarAg+NLGP vaccination helps in greater survival of the memory precursor effector cells at the peak of the effector response and their maintenance as mature memory cells, in comparison to single modality treatment. Such response is corroborated with the reduced phosphorylation of FOXO in the cytosol and increased KLF2 in the nucleus associated with enhanced CD62L, CCR7 expression of lymph node-resident CD8(+) T cells. However, spleen-resident CD8(+) T memory cells show superior efficacy for immediate memory-to-effector cell conversion. The data support in all aspects that SarAg+NLGP demonstrate superiority than SarAg vaccination alone that benefits the host by rapid effector functions whenever required, whereas, central memory cells are thought to replenish the memory cell pool for ultimate sustained disease free survival till 60 days following post-vaccination tumor inoculation. PMID- 26851530 TI - A new website to aid the interpretation of antemortem dental records:www.internationaldentalcharts.org. AB - The INTERPOL (International Police Organization) Disaster Victim Identification forms represent a global standard for mass disasters and the collection of international ante-mortem dental records. These records can now be interpreted more easily with the help of a new online dictionary of dental terminology for translating dental charts from several languages into English. The free website launched in 2013 (www.internationaldentalcharts.org) is the result of a M.Sc project on international dental charts: Guide of International Dental Charts translated into English decoding international ante-mortem dental charts for INTERPOL's Ante-mortem (AM) Disaster Victim Identification (DVI) forms (Section F2), completed in 2011. The aim of this study was to analyze the tooth numbering system, symbols and abbreviations used on dental charting worldwide. A letter was sent to the national dental associations of the 188 INTERPOL member countries, addressing the goals of the project and asking for samples of dental charts. A total of 45 countries replied and 32 common dental alterations were selected for translation, such as: decay, filling and extraction. Their symbols and/or abbreviations used were summarized in various languages. More than one system of dental notations was used in the same country whereas there was an absence of standard systems in other countries. Some of the samples of charts received were of little value. However, a fair amount of useful information and detail was found in most of them. This free consultation website could be useful when the handwriting, symbols, and abbreviations on the ante-mortem dental charts are not clear. It will be particularly applicable when ante-mortem xrays and casts are not available. PMID- 26851531 TI - Targeting inflammatory mediators with ferulic acid, a dietary polyphenol, for the suppression of monosodium urate crystal-induced inflammation in rats. AB - AIMS: The aim of this study was to investigate the anti-inflammatory effect of ferulic acid, a dietary phenol, on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. For the purpose of comparison, colchicine was used as a reference drug. MAIN METHODS: Paw edema, levels/activities of elastase, lysosomal enzymes (acid phosphatase and beta-galactosidase), nitric oxide, lipid peroxidation, antioxidant status and pro inflammatory cytokines (tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta), and histology of ankle joints were evaluated in rats with MSU crystal-induced inflammation. The messenger RNA (mRNA) expression of pro inflammatory cytokines (TNF-alpha and IL-1beta), NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasomes, caspase-1, and the transcription factor nuclear factor kappa B p65 (NF-kappaB p65) was determined by real-time polymerase chain reaction (PCR) analysis. The protein expression of NF-kappaB p65 and TNF-alpha was detected by immunohistochemical analysis. Further, a molecular docking analysis was conducted to determine the ligand efficiency of ferulic acid towards NF-kappaB, apoptosis associated speck-like protein containing a CARD (PYCARD/ASC), NLRP3, and pro caspase-1. KEY FINDINGS: In the joint homogenate of rats with MSU crystal-induced inflammation, treatment with ferulic acid (30mg/kg body weight (b.wt)) decreased paw edema; the level/activity of elastase, lysosomal enzymes, nitric oxide, lipid peroxidation, and pro-inflammatory cytokines (TNF-alpha and IL-1beta); and the mRNA expression of NLRP3 inflammasomes, caspase-1, pro-inflammatory cytokines, and NF-kappaB p65. In addition, the protein expression of NF-kappaB p65 and TNF alpha was also found to be significantly decreased. However, the antioxidant status (superoxide dismutase (SOD) and catalase (CAT)) were found to be increased. The molecular docking analysis showed that ferulic acid exhibited significant ligand efficiency towards pro-caspase-1, NF-kappaB, PYCARD/ASC, and NLRP3. SIGNIFICANCE: Our findings demonstrate the potential anti-inflammatory effect of ferulic acid on MSU crystal-induced inflammation in rats. PMID- 26851532 TI - Oxidative stress and metabolic disorders: Pathogenesis and therapeutic strategies. AB - Increased body weight and metabolic disorder including insulin resistance, type 2 diabetes and cardiovascular complications together constitute metabolic syndrome. The pathogenesis of metabolic syndrome involves multitude of factors. A number of studies however indicate, with some conformity, that oxidative stress along with chronic inflammatory condition pave the way for the development of metabolic diseases. Oxidative stress, a state of lost balance between the oxidative and anti-oxidative systems of the cells and tissues, results in the over production of oxidative free radicals and reactive oxygen species (ROS). Excessive ROS generated could attack the cellular proteins, lipids and nucleic acids leading to cellular dysfunction including loss of energy metabolism, altered cell signalling and cell cycle control, genetic mutations, altered cellular transport mechanisms and overall decreased biological activity, immune activation and inflammation. In addition, nutritional stress such as that caused by high fat high carbohydrate diet also promotes oxidative stress as evident by increased lipid peroxidation products, protein carbonylation, and decreased antioxidant system and reduced glutathione (GSH) levels. These changes lead to initiation of pathogenic milieu and development of several chronic diseases. Studies suggest that in obese person oxidative stress and chronic inflammation are the important underlying factors that lead to development of pathologies such as carcinogenesis, obesity, diabetes, and cardiovascular diseases through altered cellular and nuclear mechanisms, including impaired DNA damage repair and cell cycle regulation. Here we discuss the aspects of metabolic disorders-induced oxidative stress in major pathological conditions and strategies for their prevention and therapy. PMID- 26851533 TI - Nicotine inhibits the production of proinflammatory cytokines of mice infected with coxsackievirus B3. AB - AIMS: Although excessive sympathetic activation in viral myocarditis and the protective effects of sympathetic inhibition with beta-blockers are clear, the effects of enhancing vagal tone on viral myocarditis remain unclear. In several models, vagus nerve activation with the alpha7 nicotinic acetylcholine receptor (alpha7-nAChR) agonists has been demonstrated to ameliorate inflammation. This study was therefore designed to examine the effects of cholinergic stimulation with alpha7-nAChR agonist nicotine in a murine model of acute viral myocarditis. MATERIALS AND METHODS: BALB/C mice were infected by an intraperitoneally injection with coxsackievirus B3. Nicotine and methyllycaconitine (an alpha7 nAChR antagonist) were administered at doses of 0.4mg/kg and 0.8mg/kg three times per day for 7 or 14 consecutive days, respectively. The effects of nicotine and methyllycaconitine on survival rate, myocardial histopathological changes, cardiac function, cytokine levels, viral RNA, malondialdehyde, and superoxide dismutase contents were investigated. KEY FINDINGS: Nicotine significantly increased survival rate of the infected mice, decreased myocardial inflammation, and improved the impairment of left ventricular function in murine coxsackievirus B3-induced myocarditis compared with methyllycaconitine. The proinflammatory cytokines TNF-alpha, IL-1beta, IL-6 and IL-17A were significantly decreased in the infected mice treated with nicotine compared with methyllycaconitine. Nicotine had no significant anti-oxidative and antiviral effects in coxsackievirus B3-infected mice. SIGNIFICANCE: The results indicate that cholinergic stimulation with nicotine significantly reduced the severity of viral myocarditis in mice. The findings suggest that alpha7 nAChR agonists may be a promising new strategy for patients with myocarditis. PMID- 26851534 TI - Function of SOD1, SOD2, and PI3K/AKT signaling pathways in the protection of propofol on spinal cord ischemic reperfusion injury in a rabbit model. AB - AIMS: To verify that co-application of propofol preconditioning and postconditioning protects spinal cord from ischemia/reperfusion injury by enhancing the different subtypes of SOD activity, which is related to PI3K/AKT signal pathway. MATERIALS AND METHODS: 60 rabbits were randomly equally assigned to 3 groups: Group S, sham-operation group; Group I/R., ischemia/reperfusion group; Group P, ischemia/reperfusion group with propofol treatment. Four rabbits per group were randomly executed at the time-points: days 1, 2, 3, 5, and 7 post surgery. Spinal cord tissues at L3 to L4 levels were harvested. The bioactivities of SOD1 and SOD2, and the mRNA expression levels of SOD1, SOD2, PI3K, and AKT were detected. KEY FINDINGS: On day 1, the bioactivity of SOD1 increased significantly in Group I/R or Group P compared with Group S (P<0.05). On day 2, compared with Group S, the bioactivity of SOD1 increased significantly in Group P (P<0.05). On days 3, 5, and 7, the bioactivity of SOD1 decreased significantly respectively in Group I/R compared with Group S (P<0.05). On all timepoints, the bioactivity of SOD2 decreased significantly in Group I/R compared with Group S (P<0.05). There was a positive correlation between the SOD1 activity and the respective mRNA expression of SOD1, PI3K, and AKT. SIGNIFICANCE: Co-application of propofol preconditioning and postconditioning resulted in potent protective effects against spinal cord ischemia/reperfusion injury, which was associated with the increased expression of SOD1 in spinal cord tissues by activating PI3K/AKT signal pathway. PMID- 26851535 TI - Spiro sugar-isoxazolidine scaffold as useful polyfunctional building block for peptidomimetics design. AB - Spiro sugar-isoxazolidines obtained by 1,3-dipolar cycloaddition of activated exo glycals and nitrones were efficiently functionalized at two sites, i.e. C-4 and C 7, with arginine, arginine mimetics and guanidylated appendages. Two bicyclic sugar derivatives differing by the configuration at C-7 were chosen as model compounds. The small library of peptidomimetics was evaluated toward inhibition of VEGF-A165/neuropilin-1 binding. Unexpected cleavage of C3-C4 bond of isoxazolidine moiety was observed during hydrogenolysis and opened thus a new way toward hemiketal structures which could also find interesting applications as less constrained scaffold. PMID- 26851536 TI - Synthesis of type 2 Lewis antigens via novel regioselective glycosylation of an orthogonally protected lactosamine diol derivative. AB - The novel and efficient synthesis of type 2 Lewis antigens is reported in this study. The rationally designed lactosamine-3,2'-diol derivative with an orthogonal set of protecting groups is efficiently glycosylated with a benzyl protected 1-thio-l-fucoside donor in a unique regioselective manner to produce Lewis x (Le(x)) and Lewis y (Le(y)) derivatives in good yields. These derivatives can be prepared not only exclusively but also synchronously by choosing the appropriate reaction temperature and donor-acceptor molar ratio. The Le(x) derivatives are easily converted into sulfated or non-sulfated Le(x) bearing a terminal azido functionalized oligo-(ethyleneoxide) linker; the Le(y) derivative having the same linker can also be prepared, all of which can be further used for the chemical modification of other compounds and materials. PMID- 26851538 TI - TOEING THE LINE (OR DOING A DELICATE DANCE?): THE COURTS AND THE CLINICIANS. AB - This comment responds to the comment by Jonathan Youngs in St George's Healthcare NHS Trust v P(1) entitled 'Can the courts force the doctor's hand?' Vol. 24, No. 1, pp. 99-111, doi: 10.1093/medlaw/fwv042. It clarifies an important factual error in that comment as to the nature of the order made by the court, and it provides further observations upon the respective role of courts and clinicians in cases involving medical treatment decisions. PMID- 26851537 TI - Interdependent Barriers to Providing Adolescents with Long-Acting Reversible Contraception: Qualitative Insights from Providers. AB - STUDY OBJECTIVE: Long-acting reversible contraceptive (LARC) methods are the most effective form of reversible contraception but are underutilized by adolescents. The purpose of this study was to identify the context-specific barriers to providing adolescents with LARC that are experienced by pediatricians, family medicine physicians, and advanced practice nurses (APNs). DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: Pediatricians, family medicine providers, and APNs (n = 16) who care for adolescents participated in semistructured qualitative interviews. Interview data were analyzed using a modified grounded theory approach. MAIN OUTCOME MEASURES: Pediatricians, family medicine physicians, and APNs self-reported attitudes and practices regarding LARC provision to adolescents. RESULTS: Provider confidence in LARC, patient-centered counseling on LARC, and instrumental supports for LARC all work interdependently either in support of or in opposition to provision of LARC to adolescents. Low provider confidence in LARC for adolescents was characterized by confusion about LARC eligibility criteria and perceptions of LARC insertion as traumatic for adolescents. Patient-centered counseling on LARC required providers' ability to elicit patient priorities, highlight the advantages of LARC over other methods, and address patients' concerns about these methods. Instrumental support for LARC included provider training on LARC, access to and financial support for LARC devices, and opportunity to practice LARC insertion and counseling skills. CONCLUSION: Although none of the identified essential components of LARC provision to adolescents exist in isolation, instrumental support like provider training on LARC and access to LARC devices have the most fundamental effect on the other components and on providers' attitudes and practices regarding LARC for adolescents. PMID- 26851539 TI - Genome-wide transcriptome analysis in the ovaries of two goats identifies differentially expressed genes related to fecundity. AB - The goats are widely kept as livestock throughout the world. Two excellent domestic breeds in China, the Laiwu Black and Jining Grey goats, have different fecundities and prolificacies. Although the goat genome sequences have been resolved recently, little is known about the gene regulations at the transcriptional level in goat. To understand the molecular and genetic mechanisms related to the fecundities and prolificacies, we performed genome-wide sequencing of the mRNAs from two breeds of goat using the next-generation RNA-Seq technology and used functional annotation to identify pathways of interest. Digital gene expression analysis showed 338 genes were up-regulated in the Jining Grey goats and 404 were up-regulated in the Laiwu Black goats. Quantitative real-time PCR verified the reliability of the RNA-Seq data. This study suggests that multiple genes responsible for various biological functions and signaling pathways are differentially expressed in the two different goat breeds, and these genes might be involved in the regulation of goat fecundity and prolificacy. Taken together, our study provides insight into the transcriptional regulation in the ovaries of 2 species of goats that might serve as a key resource for understanding goat fecundity, prolificacy and genetic diversity between species. PMID- 26851540 TI - sMicroRNA-1290 inhibits cells proliferation and migration by targeting FOXA1 in gastric cancer cells. AB - BACKGROUND/AIMS: Gastric cancer is the third leading cause of cancer-related deaths in the world with high mortality rate due to the lack of markers in early detection and effective therapies. MicroRNAs (miRNAs), a critical part of epigenetic regulations in tumor, have been shown to be closely related to the initiation, development, invasion, metastasis and prognosis of gastric cancer. The present study aims to investigate the expression of miR-1290 in gastric tumor cells and to elucidate the target gene of miR-1290 in SGC-7901 gastric cancer cells. METHODOLOGY: The fluorescence in situ hybridization, real time PCR and Western blot were used to investigate the expression of miR-1290 in gastric tumor cells and clinical gastric tumor samples. The effect of miR-1290 expression on gastric tumor cells was studied using Synthetic miR-1290 inhibitor transfection, in vitro wound healing assay and flow cytometry analysis. Bioinformatics and Luciferase reporter assay were used to predict and validate the target gene of miR-1290. RESULTS: Our results revealed that miR-1290 was highly expressed in SGC 7901 gastric cancer cells as well as in clinical gastric cancer samples, which was correlated with clinical stages, depth of invasion and lymph node metastasis. Synthetic miR-1290 inhibitor transfection significantly inhibited the proliferation and migration of SGC-7901 cells. Bioinformatics analysis and luciferase reporter assay suggested that miR-1290 functioned in gastric cancer cells by targeting FOXA1 gene. CONCLUSION: miR-1290 promotes gastric tumor cells proliferation and metastasis through FOXA1, which could be used as a marker for diagnosis and a target for therapeutic intervention. PMID- 26851541 TI - Sealing frequency of B104 cells declines exponentially with decreasing transection distance from the axon hillock. AB - Transection of nerve axons (axotomy) leads to rapid (Wallerian) degeneration of the distal portion of the severed axon whereas the proximal portion and the soma often survive. Clinicians and neuroscientists have known for decades that somal survival is less likely for cells transected nearer to the soma, compared to further from the soma. Calcium ion (Ca(2+)) influx at the cut axonal end increases somal Ca(2+) concentration, which subsequently activates apoptosis and other pathways that lead to cell death. The same Ca(2+) influx activates parallel pathways that seal the plasmalemma, reduce Ca(2+) influx, and thereby enable the soma to survive. In this study, we have examined the ability of transected B104 axons to seal, as measured by uptake or exclusion of fluorescent dye, and quantified the relationship between sealing frequency and transection distance from the axon hillock. We report that sealing frequency is maximal at about 150MUm (MUm) from the axon hillock and decreases exponentially with decreasing transection distance with a space constant of about 40MUm. We also report that after Ca(2+) influx is initiated, the curve of sealing frequency versus time is well-fit by a one-phase, rising exponential model having a time constant of several milliseconds that is longer nearer to, versus further from, the axon hillock. These results could account for the increased frequency of cell death for axotomies nearer to, versus farther from, the soma of many types of neurons. PMID- 26851542 TI - Amelioration of non-motor dysfunctions after transplantation of human dopamine neurons in a model of Parkinson's disease. AB - BACKGROUND: Patients suffering from Parkinson's disease (PD) display cognitive and neuropsychiatric dysfunctions, especially with disease progression. Although these impairments have been reported to impact more heavily upon a patient's quality of life than any motor dysfunctions, there are currently no interventions capable of adequately targeting these non-motor deficits. OBJECTIVES: Utilizing a rodent model of PD, we investigated whether cell replacement therapy, using intrastriatal transplants of human-derived ventral mesencephalic (hVM) grafts, could alleviate cognitive and neuropsychiatric, as well as motor, dysfunctions. METHODS: Rats with unilateral 6-hydroxydopamine lesions to the medial forebrain bundle were tested on a complex operant task that dissociates motivational, visuospatial and motor impairments sensitive to the loss of dopamine. A subset of lesioned rats received intrastriatal hVM grafts of ~9 weeks gestation. Post graft, rats underwent repeated drug-induced rotation tests and were tested on two versions of the complex operant task, before post-mortem analysis of the hVM tissue grafts. RESULTS: Post-graft behavioural testing revealed that hVM grafts improved non-motor aspects of task performance, specifically visuospatial function and motivational processing, as well as alleviating motor dysfunctions. CONCLUSIONS: We report the first evidence of human VM cell grafts alleviating both non-motor and motor dysfunctions in an animal model of PD. This intervention, therefore, is the first to improve cognitive and neuropsychiatric symptoms long-term in a model of PD. PMID- 26851543 TI - Hepatitis B virus infection among pregnant women in Haiti: A cross-sectional serosurvey. AB - BACKGROUND: Hepatitis B vaccine administered shortly after birth is highly effective in preventing mother to child transmission (MTCT) of infection. While hepatitis B vaccine was introduced in Haiti as part of a combined pentavalent vaccine in 2012, a birth dose is not yet included in the immunization schedule. OBJECTIVES: Determine the seroprevalence of hepatitis B virus (HBV) infection among pregnant women to evaluate the risk of MTCT. STUDY DESIGN: We selected 1364 residual serum specimens collected during a 2012 human immunodeficiency virus (HIV) sentinel serosurvey among pregnant women attending antenatal care clinics. Haiti was stratified into two regions: West, which includes metropolitan Port-au Prince, and non-West, which includes all other departments. We evaluated the association between demographic and socioeconomic characteristics and HIV infection with HBV infection. RESULTS: Of 1364 selected specimens, 1307 (96%) were available for testing. A total of 422 specimens (32.7%) tested positive for total anti-HBc (38.2% in West vs. 27% in non-West, p<0.001), and 33 specimens (2.5%) were HBsAg positive (2.1% in West vs. 3% in non-West, p=0.4). Of HBsAg positive specimens, 79% had detectable HBV DNA. Women aged 30 and older had more than double the odds of positive total anti-HBc than women aged 15-19 years (p<0.001). Women with secondary (adjusted odds ratio (aOR)=0.54; 95% CI: 0.36 0.81) and post-secondary education (aOR=0.40, 95% CI: 0.19-0.79) had lower odds of total anti-HBc positivity compared with women with no education. HIV-status was not associated with HBV infection. CONCLUSIONS: Haiti has an intermediate endemicity of chronic HBV infection with high prevalence of positive HBV DNA among chronically infected women. Introduction of a universal birth dose of hepatitis B vaccine might help prevent perinatal HBV transmission. PMID- 26851545 TI - Winter precipitation and snow accumulation drive the methane sink or source strength of Arctic tussock tundra. AB - Arctic winter precipitation is projected to increase with global warming, but some areas will experience decreases in snow accumulation. Although Arctic CH4 emissions may represent a significant climate forcing feedback, long-term impacts of changes in snow accumulation on CH4 fluxes remain uncertain. We measured ecosystem CH4 fluxes and soil CH4 and CO2 concentrations and (13) C composition to investigate the metabolic pathways and transport mechanisms driving moist acidic tundra CH4 flux over the growing season (Jun-Aug) after 18 years of experimental snow depth increases and decreases. Deeper snow increased soil wetness and warming, reducing soil %O2 levels and increasing thaw depth. Soil moisture, through changes in soil %O2 saturation, determined predominance of methanotrophy or methanogenesis, with soil temperature regulating the ecosystem CH4 sink or source strength. Reduced snow (RS) increased the fraction of oxidized CH4 (Fox) by 75-120% compared to Ambient, switching the system from a small source to a net CH4 sink (21 +/- 2 and -31 +/- 1 mg CH4 m(-2) season(-1) at Ambient and RS). Deeper snow reduced Fox by 35-40% and 90-100% in medium- (MS) and high- (HS) snow additions relative to Ambient, contributing to increasing the CH4 source strength of moist acidic tundra (464 +/- 15 and 3561 +/- 97 mg CH4 m( 2) season(-1) at MS and HS). Decreases in Fox with deeper snow were partly due to increases in plant-mediated CH4 transport associated with the expansion of tall graminoids. Deeper snow enhanced CH4 production within newly thawed soils, responding mainly to soil warming rather than to increases in acetate fermentation expected from thaw-induced increases in SOC availability. Our results suggest that increased winter precipitation will increase the CH4 source strength of Arctic tundra, but the resulting positive feedback on climate change will depend on the balance between areas with more or less snow accumulation than they are currently facing. PMID- 26851544 TI - Regulation of different human NFAT isoforms by neuronal activity. AB - Nuclear factor of activated T-cells (NFAT) is a family of transcription factors comprising four calcium-regulated members: NFATc1, NFATc2, NFATc3, and NFATc4. Upon activation by the calcium-dependent phosphatase calcineurin (CaN), NFATs translocate from cytosol to the nucleus and regulate their target genes, which in the nervous system are involved in axon growth, synaptic plasticity, and neuronal survival. We have shown previously that there are a number of different splice variants of NFAT genes expressed in the brain. Here, we studied the subcellular localizations and transactivation capacities of alternative human NFAT isoforms in rat primary cortical or hippocampal neurons in response to membrane depolarization and compared the induced transactivation levels in neurons to those obtained from HEK293 cells in response to calcium signaling. We confirm that in neurons the translocation to the nucleus of all NFAT isoforms is reliant on the activity of CaN. However, our results suggest that both the regulation of subcellular localization and transcriptional activity of NFAT proteins in neurons is isoform specific. We show that in primary hippocampal neurons NFATc2 isoforms have very fast translocation kinetics, whereas NFATc4 isoforms translocate relatively slowly to the nucleus. Moreover, we demonstrate that the strongest transcriptional activators in HEK293 cells are NFATc1 and NFATc3, but in neurons NFATc3 and NFATc4 lead to the highest induction, and NFATc2 and NFATc1 display isoform-specific transcription activation capacities. Altogether, our results indicate that the effects of calcium signaling on the action of NFAT proteins are isoform-specific and can differ between cell types. We show that the effects of calcium signaling on the action of NFAT proteins are isoform-specific and differ between cell types. Although nuclear localization of all NFAT isoforms in neurons requires calcineurin, the subcellular distributions, neuronal activity-induced nuclear translocation extent and kinetics, and transcription activation capacities of alternative NFAT proteins vary. PMID- 26851546 TI - Aortic perforation following transcatheter aortic valve deployment. PMID- 26851548 TI - Noise exposure of immature rats can induce different age-dependent extra-auditory alterations that can be partially restored by rearing animals in an enriched environment. AB - It has been previously shown that different extra-auditory alterations can be induced in animals exposed to noise at 15 days. However, data regarding exposure of younger animals, that do not have a functional auditory system, have not been obtained yet. Besides, the possibility to find a helpful strategy to restore these changes has not been explored so far. Therefore, the aims of the present work were to test age-related differences in diverse hippocampal-dependent behavioral measurements that might be affected in noise-exposed rats, as well as to evaluate the effectiveness of a potential neuroprotective strategy, the enriched environment (EE), on noise-induced behavioral alterations. Male Wistar rats of 7 and 15 days were exposed to moderate levels of noise for two hours. At weaning, animals were separated and reared either in standard or in EE cages for one week. At 28 days of age, different hippocampal-dependent behavioral assessments were performed. Results show that rats exposed to noise at 7 and 15 days were differentially affected. Moreover, EE was effective in restoring all altered variables when animals were exposed at 7 days, while a few were restored in rats exposed at 15 days. The present findings suggest that noise exposure was capable to trigger significant hippocampal-related behavioral alterations that were differentially affected, depending on the age of exposure. In addition, it could be proposed that hearing structures did not seem to be necessarily involved in the generation of noise-induced hippocampal-related behaviors, as they were observed even in animals with an immature auditory pathway. Finally, it could be hypothesized that the differential restoration achieved by EE rearing might also depend on the degree of maturation at the time of exposure and the variable evaluated, being younger animals more susceptible to environmental manipulations. PMID- 26851549 TI - An update on biomarkers in axial spondyloarthritis. AB - Axial spondyloarthritis is a chronic inflammatory disease with the onset at a young age, and, if undiagnosed and untreated, it may result in permanent damage and lifelong disability. Rates of early diagnosis have improved, due in particular to the addition of magnetic resonance imaging into the diagnostic armamentaria; however, it is costly, not widely available, and requires experienced readers to interpret the findings. In addition to clinical measures and imaging techniques, biomarkers that will be described in this review may represent useful tools for diagnosis, monitoring disease activity and outcomes as well as therapeutic responses. Currently, HLA-B27 remains the best genetic biomarker for making a diagnosis, while CRP currently appears to be the best circulating measure for assessing disease activity, predicting structural progression and therapeutic response. Interestingly, key molecules in the pathogenesis of the disease and essential therapeutic targets, such as tumour necrosis factor (TNF)alpha, interleukin (IL)-17 and IL-23, show only limited association with disease characteristics or disease progression. Some genetic biomarkers and particularly anti-CD74 antibodies, may become a promising tool for the early diagnosis of axSpA. Further biomarkers, such as matrix metalloproteinases (MMP)-3, calprotectin (S100A8/9), vascular endothelial growth factor (VEGF), C-terminal telopeptide of type II collagen (CTX-II) or dickkopf-1 (DKK-1), are not sufficient to reflect disease activity, but may predict spinal structural progression. In addition, recent data have shown that monitoring calprotectin might represent a valuable biomarker of therapeutic response. However, all of these results need to be confirmed in large cohort studies prior to use in daily clinical practice. PMID- 26851547 TI - The highly selective orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol drinking in ethanol dependent mice. AB - The orexin/hypocretin (ORX) system plays a major role in motivation for natural and drug rewards. In particular, a number of studies have shown that ORX signaling through the orexin 1 receptor (OX1R) regulates alcohol seeking and consumption. Despite the association between ORX signaling and motivation for alcohol, no study to date has investigated what role the ORX system plays in alcohol dependence, an understanding of which would have significant clinical relevance. This study was designed to evaluate the effect of the highly selective OX1R antagonist GSK1059865 on voluntary ethanol intake in ethanol-dependent and control non-dependent mice. Mice were subjected to a protocol in which they were evaluated for baseline ethanol intake and then exposed to intermittent ethanol or air exposure in inhalation chambers. Each cycle of chronic intermittent ethanol (CIE), or air, exposure was followed by a test of ethanol intake. Once the expected effect of increased voluntary ethanol intake was obtained in ethanol dependent mice, mice were tested for the effect of GSK1059865 on ethanol and sucrose intake. Treatment with GSK1059865 significantly decreased ethanol drinking in a dose-dependent manner in CIE-exposed mice. In contrast GSK1059865 decreased drinking in air-exposed mice only at the highest dose used. There was no effect of GSK1059865 on sucrose intake. Thus, ORX signaling through the OX1R, using a highly-selective antagonist, has a profound influence on high levels of alcohol drinking induced in a dependence paradigm, but limited or no influence on moderate alcohol drinking or sucrose drinking. These results indicate that the ORX system may be an important target system for treating disorders of compulsive reward seeking such as alcoholism and other addictions in which motivation is strongly elevated. PMID- 26851551 TI - A link: Allergic rhinitis, Asthma & Systemic Lupus Erythematosus. AB - This review has discussed a link between allergic rhinitis, asthma and systemic lupus erythematosus (SLE) and a case report in this area. A clear link with symptoms of allergic rhinitis, asthma and SLE exists. Several articles found on pubmed in the literature are listed on allergic rhinitis and allergy, Th1-immune responses, mast cells in autoimmunity, total immunoglobulin E levels in lupus, atopic diseases and SLE are reviewed. In addition, risks and correlations, genetic predisposition, environmental factors, immune regulation, elevated serum IgE levels, regulatory B cells for both allergic and autoimmune diseases are mentioned, Asthma and the vascular endothelial cell growth factor, asthma and autoimmune diseases, allergy and autoimmunity, neutrophils, innate and adaptive immunity in the development of SLE, the (Tim) gene family, complement activation in SLE and immunomodulation, hypersensitivity reactions in autoimmunity are discussed. PMID- 26851550 TI - Granulomatosis with polyangiitis and facial palsy: Literature review and insight in the autoimmune pathogenesis. AB - Granulomatosis with polyangiitis (GPA) is an autoimmune systemic necrotizing small-vessel vasculitis associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). Oto-neurological manifestations of ANCA-associated vasculitis according to PR3-ANCA positivity and MPO-ANCA positivity are usually reported. Facial nerve palsy is usually reported during the clinical course of the disease but it might appear as the presenting sign of GPA. Necrotizing vasculitis of the facial nerve 'vasa nervorum' is nowadays the most widely accepted etiopathogenetic theory to explain facial damage in GPA patients. A central role for PR3-ANCA in the pathophysiology of vasculitis in GPA patients with oto-neurological manifestation is reported. GPA requires prompt, effective management of the acute and chronic manifestations. Once the diagnosis of GPA has been established, clinicians should devise an appropriate treatment strategy for each individual patient, based on current clinical evidence, treatment guidelines and recommendations. PMID- 26851552 TI - Improving medication adherence in bipolar disorder: A systematic review and meta analysis of 30 years of intervention trials. AB - BACKGROUND: Medication non-adherence in bipolar disorder is a significant problem resulting in increased morbidity, hospitalisation and suicide. Interventions to enhance adherence exist but it is not clear how effective they are, or what works and why. METHODS: We systematically searched bibliographic databases for RCTs of interventions to support adherence to medication in bipolar disorder. Study selection and data extraction was performed by two investigators. Data was extracted on intervention design and delivery, study characteristics, adherence outcomes and study quality. The meta-analysis used pooled odds ratios for adherence using random effects models. RESULTS: Searches identified 795 studies, of which 24 met the inclusion criteria, 18 provided sufficient data for meta analysis. The pooled OR was 2.27 (95% CI 1.45-3.56) equivalent to a two-fold increase in the odds of adherence in the intervention group relative to control. Smaller effects were seen where the control group consisted of an active comparison and with increasing intervention length. The effects were robust across other factors of intervention and study design and delivery. LIMITATIONS: Many studies did not report sufficient information to classify intervention design and delivery or judge quality and the interventions were highly variable. Therefore, the scope of moderation analysis was limited. CONCLUSIONS: Even brief interventions can improve medication adherence. Limitations in intervention and study design and reporting prevented assessment of which elements of adherence support are most effective. Applying published guidance and quality criteria for designing and reporting adherence interventions is a priority to inform the implementation of cost-effective adherence support. PMID- 26851553 TI - Inhibiting neuroinflammation: The role and therapeutic potential of GABA in neuro immune interactions. AB - The central nervous system, once thought to be a site of immunological privilege, has since been found to harbour immunocompetent cells and to communicate with the peripheral nervous system. In the central nervous system (CNS), glial cells display immunological responses to pathological and physiological stimuli through pro- and anti-inflammatory cytokine and chemokine signalling, antigen presentation and the clearing of cellular debris through phagocytosis. While this neuroinflammatory signalling can act to reduce neuronal damage and comprises a key facet of CNS homeostasis, persistent inflammation or auto-antigen-mediated immunoreactivity can induce a positive feedback cycle of neuroinflammation that ultimately results in necrosis of glia and neurons. Persistent neuroinflammation has been recognised as a major pathological component of virtually all neurodegenerative diseases and has also been a focus of research into the pathology underlying psychiatric disorders. Thus, pharmacological strategies to curb the pathological effects of persistent neuroinflammation are of interest for many disorders of the CNS. Accumulating evidence suggests that GABAergic activities are closely bound to immune processes and signals, and thus the GABAergic neurotransmitter system might represent an important therapeutic target in modulating neuroinflammation. Here, we review evidence that inflammation induces changes in the GABA neurotransmitter system in the CNS and that GABAergic signalling exerts a reciprocal influence over neuroinflammatory processes. Together, the data support the hypothesis that the GABA system is a potential therapeutic target in the modulation of central inflammation. PMID- 26851554 TI - High-repetition rate laser ablation coupled to dielectric barrier discharge postionization for ambient mass spectrometry. AB - Most ambient sample introduction and ionization techniques for native mass spectrometry are highly selective for polar agents. To achieve a more general sensitivity for a wider range of target analytes, a novel laser ablation dielectric barrier discharge (LA DBD) ionization scheme was developed. The approach employs a two-step mechanism with subsequent sample desorption and post ionization. Effective ablation was achieved by the second harmonic output (lambda=532nm) of a diode pumped Nd:YVO4 laser operating at a high-repetition rate of several kHz and pulse energies below 100MUJ. The ejected analyte containing aerosol was consecutively vaporized and ionized in the afterglow of a DBD plasma jet. Depending on their proton affinity the superexcited helium species in this afterglow produced analyte ions as protonated and ammoniated species, as well as radical cations. The optimization procedure could corroborate underlying conceptual consideration on the ablation, desorption and ionization mechanisms. A successful detection of a variety of target molecules could be shown from the pharmaceutical ibuprofen, urea, the amino acids l-arginine, l lysine, the polymer polyethylene glycol, the organometallic compound ferrocene and the technical mixture wild mint oil. For a reliable evaluation of the introduced detection procedure spectra from the naturally abundant alkaloid capsaicin in dried capsicum fruits were recorded. PMID- 26851555 TI - Evidence for involvement of NK3 receptors in the anxiogenic-like effect of SP6 11(C-terminal), a metabolite of substance P, in rats evaluated in the elevated plus-maze. AB - INTRODUCTION: Substance P (SP) is a neuropeptide widely expressed throughout the fear-processing pathways of the brain. SP is cleaved by several proteolytic enzymes in amino (N-) and carboxy (C-) terminal sequences, which can have biological activities per se. We have previously shown that the anxiogenic-like effects elicited by SP6-11(C-terminal), a specific metabolite of SP, are mediated via NK1 and NK2 receptors. Nevertheless, there are evidences that C-terminal fragments may have a greater affinity for NK3 receptors. OBJECTIVES: The aim of the present study was to further investigate the possible involvement of NK3 receptors in the anxiogenic-like effects induced by SP6-11(C-terminal). METHODS: Adult male Wistar rats were intracerebroventricularly (i.c.v.) treated with SR142801 (NK3 receptors antagonist) or vehicle one minute to prior SP6-11(C terminal) or vehicle. Other experimental groups received SP6-11(C-terminal) or vehicle i.c.v. one minute prior to senktide (NK3 receptors agonist) or vehicle. After five minutes, the animals were behaviorally evaluated in the elevated plus maze test (EPM). RESULTS: SR142801 (100 pmol) or SP6-11(C-terminal) (10 pmol) reduced all the parameters of open-arms exploration and increased the number of protected stretch-attend postures in the EPM, indicating an anxiogenic-like effect. Senktide (10 pmol) promoted an opposite effect on these behavioral parameters, characterizing an anxiolytic-like profile. Pretreatment with SR142801, in an ineffective dose, potentiated the SP6-11-induced anxiety, especially in the unprotected head-dipping and protected stretch-attend postures behaviors. Moreover, the anxiolytic-like effect induced by senktide (1 pmol) was prevented by SP6-11. CONCLUSIONS: Our results give support to the involvement of NK3 receptors in the anxiogenic-like actions of SP6-11(C-terminal), where this metabolite seems to behave as an antagonist, in a way similar to SR142801. PMID- 26851556 TI - Influence of SKF38393 on changes of gene profile in rat prefrontal cortex during chronic paradoxical sleep deprivation. AB - Chronic paradoxical sleep deprivation (CSD) can induce dramatic physiological and neurofunctional changes in rats, including decreased body weight, reduced learning and memory, and declined locomotor function. SKF38393, a dopamine D1 receptor agonist, can reverse the above damages. However, the mechanism of CSD syndrome and reversal role of SKF38393 remains largely unexplained. To preliminarily elucidate the mechanism of the neural dysfunction caused by CSD, in the present study we use gene chips to examine the expression profile of more than 28,000 transcripts in the prefrontal cortex (PFC). Rats were sleep deprived by modified multi-platform method for 3 weeks. Totally 59 transcripts showed differential expressions in CSD group in contrast to controls; they included transcripts coding for caffeine metabolism, circadian rhythm, drug metabolism and some amino acid metabolism pathway. Among the 59 transcripts, 39 increased their expression and 20 decreased. Two transcripts can be specifically reversed with SKF38393, one of them is Homer1, which is related to 20 functional classifications and coding for Glutamatergic synapse pathway. Our findings in the present study indicate that long-term sleep deprivation may trigger the changes of some certain functions and pathways in the PFC, and lead to the dysfunction of this advanced neuron, and the activation of D1 receptor by SKF38393 might ameliorate these changes via modulation of some transcripts such as Homer1, which is involved in the Ca(2+) pathway and MAPK pathway related to Glutamatergic synapse pathway. PMID- 26851557 TI - Neonatal proinflammatory challenge in male Wistar rats: Effects on behavior, synaptic plasticity, and adrenocortical stress response. AB - Effects of neonatal proinflammatory stress (NPS) on the development of anxiety and depressive-like behavior, stress responsiveness, hippocampal plasticity and conditioned fear response were studied in adolescent and adult male Wistar rats. On PND 3 and PND 5, the pups were subcutaneously injected with bacterial lipopolysaccharide (LPS, 50 MUg/kg). In the open field test, signs of increased anxiety were demonstrated in adolescent (PND 32), but not in adult (PND 101) rats. In the elevated plus maze, no changes could be detected in adolescent rats, however, in the adults the number of entries into the open arms decreased suggesting increased anxiety after NPS. Signs of "behavioral despair" in the forced swim test, expressed in adolescent rats as a trend, became significant in the adults indicating depression-like behavior. In the majority of brain slices from PND 19-PND 33 rats subjected to NPS, deficit of LTP in the hippocampal CA1 field was detected, this deficit being associated with the impaired mechanisms of LTP induction. In the adult rats, NPS enhanced fear conditioning promoting improved formation of the novel context-foot shock association in the contextual fear conditioning paradigm without effect on cued fear conditioning. NPS significantly impaired functioning of the hypothalamic-pituitary-adrenal axis (HPAA), resulting in an elevated corticosterone level maintained in the adolescents but not in the adults and in modified corticosterone response to behavioral sub-chronic stress in both adolescent and adult rats. Thus, NPS induces "perinatal malprogramming" resulting in development of depression-like behaviors, associated with abnormalities in functioning of the HPAA, impaired hippocampal neuroplasticity (LTP) and changes in hippocampus-dependent memory formation. PMID- 26851558 TI - Combined implant-residual tooth supported prosthesis after tooth hemisection: A finite element analysis. AB - Tooth hemisection preserves partial tooth structure and reduces the resorption of alveolar bone. The aim of this study was to analyze the feasibility of preserving a molar after hemisection and inserting a dental implant with different prosthetic superstructures by means of finite element analysis. First, the distance between the root of the mandibular second premolar and the distal root of the first molar were measured in 80 cone beam computed tomography (CBCT) data sets. Based on these data, the lower right posterior jaw segment was reconstructed and the geometries of the appropriate implant were imported. Four models were created: (1) Hemi-1: An implant (3.7*9mm) replaced the mesial root of the molar, and a single crown was placed on the implant and residual tooth. (2) Hemi-2: Two separate crowns were generated for the implant and the residual tooth. (3) Single: An implant (5.5*9mm) with crown replaced the whole molar. (4) FPD: A 3-unit fixed partial denture combined the distal residual part of the molar and premolar. The results indicated that stresses in the cortical bone and strains in the majority region of the spongious bone were below the physiological upper limits. There were higher stresses in implant with the Hemi-1 and Single models, which had the same maximum values of 45.0MPa. The FPD models represented the higher values of stresses in the teeth and strains in PDL compared to other models. From a biomechanical point of view, it can be concluded that a combination of an implant and residual molar after tooth hemisection is an acceptable treatment option. PMID- 26851559 TI - Assessment of mandibular posterior regional landmarks using cone-beam computed tomography in dental implant surgery. AB - The aim of this study has been to evaluate and correlate the anatomical features of the posterior mandibular region (submandibular fossa depth, bone height and thickness, and mandibular canal corticalization) to improve accident prevention and allow safe planning in implantology. Four parasagittal sections of cone-beam computed tomography (CBCT) from 100 patients were bilaterally analyzed. Linear measurements of the submandibular fossa depth, bone height and thickness were performed. The submandibular fossa was also classified into non-influential undercuts and influential undercuts for implant placement. Mandibular canal corticalization was also evaluated and classified according to the visualization. Data on patient age and gender were also collected. Forty-one scans (41%) were from male patients, and 59 (59%) were from female patients. Patient age ranged between 18 and 84 years, with an average age of 51.37 years. The submandibular fossa depth and implant bone thickness had a significant effect on the variability of the sample (46.1% and 22.3%, respectively). The submandibular fossa depth was quite variable, and the highest values were observed in the posterior regions. In 18.27% of the cases, the presence of the fossa directly influenced implant placement, considering a bone height of 10mm (standard implant). A significant correlation was observed between fossa depth and bone thickness. Thus, greater attention should be paid to thick ridges; although thick ridges are favorable, they may be associated with deeper submandibular fossae. The mandibular canal was the most influential anatomical structure in the premolar region due to the reduced bone height in this region and the greater difficulty in viewing the canal, and the submandibular fossa was the most influential structure in the molar region due to lower bone height leading up to the fossa and the greater fossa depth in this region. Therefore, CBCT is an important tool for assessing the mandibular region and planning for safe implant installation in the posterior mandible. Furthermore, comprehensive evaluation of the characteristics of this region is necessary, as the variables - submandibular fossa depth, bone height and thickness, and mandibular canal corticalization - are related and must be considered together when planning. PMID- 26851560 TI - Tannic acid alleviates lead acetate-induced neurochemical perturbations in rat brain. AB - Oxidative stress has been projected as a promising mechanism involved in lead exposure. The lead predisposition catalyzes oxidative reactions and generates reactive oxygen species. The present study was carried out to investigate the effect of oral administration of tannic acid (TA) on behavioral deficit, antioxidative deterioration induced by lead acetate (LA) exposure on experimental rat brain. Male Wistar rats were treated with 50mg/kg body weight of LA and TA for three times a week for two weeks. Our data showed LA-induced profound elevation of ROS production and oxidative stress, as evidenced by increased levels of oxidative stress markers such as lipid peroxidation and protein carbonyl observed in LA treated rats, whereas significant depletion in the activity of non-enzymatic antioxidants, enzymatic antioxidants, neurotoxicity biomarker and histological changes were observed in LA treated rat brain. However, TA administration restored antioxidant status of brain significantly when compared to control. Our results demonstrate that TA exhibits potent antioxidant properties and suppresses oxidative damages in rat brain induced by LA treatment. These findings were further supported by the neurotoxicity biomarker and histopathological findings in the brain tissue showed that TA protected tissue from deleterious effects of LA exposure. It is concluded, these data suggest that LA induces oxidative stress and supplementation of TA has a powerful antioxidant effect, and it protected rat brain from poisonous effect of LA exposure in experimental rat. PMID- 26851562 TI - Which Aspirin Dose and Preparation Is Best for the Long-Term Prevention of Cardiovascular Disease and Cancer? Evidence From a Systematic Review and Network Meta-Analysis. AB - The evidence base on aspirin in primary prevention suggests that it can reduce significantly the risk of cardiovascular disease (CVD) events and cancer, especially colorectal, albeit increasing bleeding. There is, however, uncertainty on the optimal aspirin dose and preparation for primary prevention. We thus aimed to review main sources of evidence informing on daily dosage and preparation of aspirin for primary prevention of CVD and cancer. We collected and elaborated aspirin effectiveness and safety data from U.S. Preventive Services Task Force reports on aspirin in primary prevention, distinguishing average daily dose in <100mg, 100mg, and >100mg. The following preparations were also systematically compared: enteric coated, controlled release, non-coated, or otherwise unspecified. Fixed-effect pairwise and network meta-analytic models were run in a frequentist framework. Eleven randomized trials were shortlisted, enrolling 104,101 subjects, followed for a median of 60months. At pairwise analysis, aspirin was associated with significant reductions in death and CVD events, non significant reductions in cancer death or incidence, and significant increases in the risk of intracranial and gastrointestinal (GI) bleeding. An average daily dose of 100mg had the highest probability of reducing death, cancer death, and cancer incidence, whereas higher doses seemed superior for reducing CVD events, and 100mg or less daily proved better tolerated. Coated preparations appeared more beneficial for death, cancer death, cancer incidence, and GI bleeding, whereas controlled release preparations appeared better for CVD events and non coated ones for intracranial bleeding. In conclusion, an average daily dose of 100mg of coated aspirin seems more likely to confer favorable preventive effects on death and cancer, with higher doses more appealing for CVD prevention and lower doses better tolerated. PMID- 26851563 TI - Comparative studies of cervical spine anterior stabilization systems--Finite element analysis. AB - BACKGROUND: The object of the study was to assess the impact of one-level stabilization of the cervical spine for both anterior static and dynamic plates. Segments C2-C6 of the cervical spine, were investigated, from which was determined the stress and strain fields in the region of implantation and adjacent motion segments. The purpose was the comparison of changes that affect the individual stabilizers. METHODS: For testing we used finite element analysis. The cervical spine model takes into account local spondylodesis. The study includes both an intact anatomical model and a model with implant stabilization. FINDINGS: The analysis covered the model loaded with a moment of force for 1 Nm in the sagittal plane during movement. We compared both the modeled response of the whole fragment C2-C6 and the response of individual motion segments. The largest limitation of range of motion occurred after implantation with static plates. The study also showed that the introduction of the one-level stabilization resulted in an increase in stress in intervertebral disc endplates of adjacent segments. INTERPRETATION: The results indicate that the increase in stress caused by stiffening may result in disorders in remodeling of bone structures. The use of dynamic plates showed improved continuity strains in the tested spine, thereby causing remodeling most similar to the physiological state and reducing the stresses in adjacent segments. PMID- 26851564 TI - Differences in hip-knee joint coupling during gait after anterior cruciate ligament reconstruction. AB - BACKGROUND: After anterior cruciate ligament injury, patients have increased risk for developing degenerative osteoarthritis, potentially due to the kinematic changes that persist after surgical reconstruction. Current research only describes single joint kinematic differences rather than the way in which two joints behave concurrently, termed joint coupling. The purpose of this study was to compare knee motion relative to hip motion in anterior cruciate ligament reconstructed and healthy limbs during walking and jogging. METHODS: Thirty-seven recreationally active volunteers (22 reconstructed, 15 healthy) walked and jogged at 4.83 km/h and 9.66 km/h respectively. Vector coding methods were used to calculate stride-to-stride variability, magnitude, and vector angle of 6 joint couples during walking and jogging: hip frontal-knee frontal planes, hip frontal knee sagittal, hip frontal-knee transverse, hip sagittal-knee frontal, hip sagittal-knee transverse, and hip transverse-knee frontal planes. FINDINGS: The hip sagittal-knee frontal and hip sagittal-knee transverse joint couples had decreased variability during mid-stance, and all other couples had increased variability during the stance phase in the reconstructed group. The reconstructed group had decreased magnitude of joint excursion in the hip frontal-knee sagittal couple during all phases of gait during walking. Vector angles of the hip frontal knee transverse couple increased in the reconstructed group during the loading, middle, and terminal stance phases, and swing phase of gait during walking. INTERPRETATION: The increased variability and decreased magnitude of joint excursion indicate that movement patterns were less consistent during walking gait despite employing a more constrained system during movement in the reconstructed limb compared to healthy controls. PMID- 26851565 TI - Transfer of the long head of biceps to the conjoint tendon. A biomechanical study. AB - BACKGROUND: Tenodesis of the long head of biceps has been intensively investigated and various surgical options exist. The aim of this biomechanical study was to compare the maximum strength of two different techniques for biceps tenodesis. Our hypothesis was that the two procedures have the same biomechanical properties. METHODS: We performed the two different tenodesis techniques using 12 fresh frozen shoulders divided into two groups of six. In the first group, the biceps was transferred to the conjoint tendon. In the second group, an intraossous suprapectoral tenodesis was performed. After a preload of 10 N, cyclical loading with a maximum of 60 N and 100 N with 100 cycles and 0.5 Hz was applied to the tendons for both groups. An axial ultimate loading to failure was conducted subsequently. RESULTS: No significant differences were found in age, bone mineral density, or weight between the two groups. During the cyclical loading with 60 N, one slippage of the tendon was observed in the suprapectoral group. The mean ultimate load to failure was 294.15N in the transposition group and 186.76 N in the suprapectoral group, but this difference was not significant (P=0.18). INTERPRETATION: The biomechanical results demonstrated equal biomechanical properties postoperatively for both transposition of the tendon and the current standard suprapectoral tenodesis procedure. The transposition can be performed as a primary or a salvage procedure in order to potentially reduce the proportion of patients with persistent postoperative bicipital groove pain and is comparable in strength to a standard tenodesis. PMID- 26851561 TI - Cardiac troponin structure-function and the influence of hypertrophic cardiomyopathy associated mutations on modulation of contractility. AB - Cardiac troponin (cTn) acts as a pivotal regulator of muscle contraction and relaxation and is composed of three distinct subunits (cTnC: a highly conserved Ca(2+) binding subunit, cTnI: an actomyosin ATPase inhibitory subunit, and cTnT: a tropomyosin binding subunit). In this mini-review, we briefly summarize the structure-function relationship of cTn and its subunits, its modulation by PKA mediated phosphorylation of cTnI, and what is known about how these properties are altered by hypertrophic cardiomyopathy (HCM) associated mutations of cTnI. This includes recent work using computational modeling approaches to understand the atomic-based structural level basis of disease-associated mutations. We propose a viewpoint that it is alteration of cTnC-cTnI interaction (rather than the Ca(2+) binding properties of cTn) per se that disrupt the ability of PKA mediated phosphorylation at cTnI Ser-23/24 to alter contraction and relaxation in at least some HCM-associated mutations. The combination of state of the art biophysical approaches can provide new insight on the structure-function mechanisms of contractile dysfunction resulting cTnI mutations and exciting new avenues for the diagnosis, prevention, and even treatment of heart diseases. PMID- 26851566 TI - Implementation and evaluation of a dilation and evacuation simulation training curriculum. AB - OBJECTIVES: To evaluate obstetrics and gynecology resident physicians' performance following a simulation curriculum on dilation and evacuation (D&E) procedures. STUDY DESIGN: This study included two phases: simulation curriculum development and resident physician performance evaluation following training on a D&E simulator. Trainees participated in two evaluations. Simulation training evaluated participants performing six cases on a D&E simulator, measuring procedural time and a 26-step checklist of D&E steps. The operative training portion evaluated residents' performance after training on the simulator using mastery learning techniques. Intra-operative evaluation was based on a 21-step checklist score, Objective Structured Assessment of Technical Skills (OSATS), and percentage of cases completed. RESULTS: Twenty-two residents participated in simulation training, demonstrating improved performance from cases one and two to cases five and six, as measured by checklist score and procedural time (p<.001 and p=.001, respectively). Of 10 participants in the operative training, all performed at least three D&Es, while seven performed at least six cases. While checklist scores did not change significantly from the first to sixth case (mean for first case: 18.3; for sixth case: 19.6; p=.593), OSATS ratings improved from case one (19.7) to case three (23.5; p=.001) and to case six (26.8; p=.005). Trainees completed approximately 71.6% of their first case (range: 21.4-100%). By case six, the six participants performed 81.2% of the case (range: 14.3-100%). CONCLUSIONS: D&E simulation using a newly-developed uterine model and simulation curriculum improves resident technical skills. Simulation training with mastery learning techniques transferred to high level of performance in OR using checklist. The OSATS measured skills and showed improvement in performance with subsequent cases. IMPLICATIONS: Implementation of a D&E simulation curriculum offers potential for improved surgical training and abortion provision. PMID- 26851567 TI - Gal/GalNAc specific multiple lectins in marine bivalve Anadara granosa. AB - Complete lectin mapping of molluscs with their diversified recognition pattern and possible role in lectin-carbohydrate interaction based immune response triggering need much attention. In this communication, Gal/GalNAc specific three lectins AGL-IA (Anadara granosa lectin-IA), AGL-IB (A. granosa lectin-IB) and AGL IV (A. granosa lectin-IV) and a lectin having hemolytic activity AGL-III (A. granosa lectin-III) were purified from the plasma of A. granosa bivalve by a combination of gel filtration and affinity chromatography. AGL-IA and IB were oligomeric lectins whereas, AGL-III and IV were monomeric. The molecular weight of AGL-IA, IB, III and IV were 375, 260, 45 and 33 kDa respectively. AGL-IA and IV agglutinated both rabbit and pronase treated human erythrocytes, whereas AGL IB agglutinated only rabbit erythrocytes. AGL-III was found to agglutinate rabbit erythrocytes, however, it caused hemolysis of pronase treated human erythrocytes. The activity of all four lectins was calcium dependent and maximum at a pH range 7-8. Apart from Gal/GalNAc specific, the four lectins showed substantial differences in their carbohydrate recognition pattern. Moreover, there was a difference in the carbohydrate specificity between AGL-III and other three lectins (AGL-IA, AGL-IB and AGL-IV) towards polyvalent glycotope. On the one hand, 'cluster glycoside effect' i.e., an enhancement of the activity of a multivalent ligand, was observed for carbohydrate specificities of AGL-IA, AGL IB, AGL-IV. On the other hand, the effect of multivalent ligands on the carbohydrate specificity of AGL-III was opposite of cluster glycoside effect. The affinity of AGL-IA, AGL-IB and AGL-IV for ligands can be ranked as follows: glycoproteins >> polysaccharide > oligosaccharides and monosaccharides. However, Gal related monosaccharides were the best inhibitors of AGL-III and the inhibitory activity decreased gradually in the following order: monosaccharide > disaccharide > polysaccharide. Thus, the diverse specificity of multiple lectins in A. granosa plasma possibly enables to recognize a wide range of microorganisms. PMID- 26851568 TI - Variations of immune parameters in the lined seahorse Hippocampus erectus after infection with enteritis pathogen of Vibrio parahaemolyticus. AB - Enteritis has been increasingly recognized as one of the major obstacles for the lined seahorse Hippocampus erectus mass culture success. In the present study, the intestinal bacteria strains of the lined seahorses H. erectus suffered from enteritis were isolated, then their pathogenicities were confirmed by artificial infection, and one pathogenic bacteria strain named DS3 was obtained. The median lethal dose (LD50) of strain DS3 for 10 days was determined. The seahorses with different infection levels of uninfected (control), early stage of infection (ESI) and late stage of infection (LSI) were respectively sampled at 0, 3, 6 and 9 days post infection, and 12 immune parameters in the plasma were analyzed. The strain DS3 identified with a biochemical test combined with a molecular method was Vibrio parahaemolyticus, and its LD50 for 10 days was 1.3 * 10(3) cfu/fish. Six parameters including monocytes/leucocytes, leucocytes phagocytic rate, interleukin-2, interferon-alpha, lysozyme and immunoglobulin M exhibited a generally similar variation trend: highest in the control, second in the ESI and lowest in the LSI throughout the entire experiment. In view of the infection level of V. parahaemolyticus to H. erectus is largely decided by the seahorse's own immune capacity, therefore, these immune parameters were high in the non- or slightly infected seahorses, and low in the severely infected individuals may be an indicator for immune level. These immune parameters may be reliable indicators for the juvenile and broodstock quality assessment. Moreover, clarification of the enteritis pathogen also provides guidances for targeted medicine choice for the lined seahorse. PMID- 26851569 TI - Histological changes, apoptosis and metallothionein levels in Triturus carnifex (Amphibia, Urodela) exposed to environmental cadmium concentrations. AB - The aim of this study was to verify if the freshwater safety values established from the European Community (1998) and the Italian Ministry of Health (2001) for cadmium (44.5nM/L in drinking water and 178nM/L in sewage waters) were safe for amphibians, since at these same concentrations cadmium induced endocrine disruption in the newt Triturus carnifex. Adult male specimens of T. carnifex were exposed daily to cadmium (44.5nM/L and 178nM/L as CdCl2, nominal concentrations), respectively, during 3- and 9-months; at the same time, control newts were exposed to tap water only. The accumulation of cadmium in the skin, liver and kidney, the levels of metallothioneins in the skin and the liver, the expression of metallothionein mRNA in the liver, as well as the presence of histological alterations and of apoptosis in the target organs were evaluated. The 9-months exposure induced cadmium accumulation in all the tissues examined; moreover, histological changes were observed in all the tissues examined, irrespective of the dose or the time of exposure. Apoptosis was only detected in the kidney, whereas metallothioneins and metallothionein mRNA did not increase. This study demonstrates that the existing chronic water quality criterion established for cadmium induces in the newt T. carnifex cadmium accumulation and histological alterations in the target organs examined. Together with our previous results, showing that, at these same concentrations, cadmium induced endocrine disruption, the present results suggest that the existing chronic water quality criterion for cadmium appears to be not protective of amphibians. PMID- 26851570 TI - Zinc toxicity to the alga Pseudokirchneriella subcapitata decreases under phosphate limiting growth conditions. AB - Previous studies have suggested that phosphorus (P) deficiency can increase the sensitivity of microalgae to toxic trace metals, potentially due to reduced metal detoxification at low cell P quota. The existing evidence is, however, inconsistent. This study was set up to determine the combined effects of zinc (Zn) and P supplies on Zn and P bioaccumulation and growth of the green microalgae Pseudokirchneriella subcapitata. Zinc toxicity was investigated in (i) a 24h growth rate assay with cells varying in initial cell P quota (0.5-1.7% P on cell dry weight) with no supplemental P during Zn exposure (Expt. 1) and in (ii) a 48h growth assay initiated with cells at the end of a 14-days steady state culture at three P addition rates (RARs) between 0.8 and 1.6day(-1) (Expt.2). The solution Zn concentrations required to reduce final cell density by 10% relative to control (EbC10) were 5-fold (Expt.1) or 2-fold (Expt.2) lower at the highest P supply than at the lowest P supply, i.e. Zn was more toxic at higher P supply, in contrast with the suggestions from previous studies. Cell P quota increased with increasing Zn in the exposure solution (Expt.2), thereby partially overcoming P deficiency under moderate Zn toxicity compared to low Zn exposure. Similarly, cell Zn increased with increasing P supply, potentially induced by Zn-P complexation or precipitation inside the cell. A dynamic growth model accounting for effects of external Zn and internal P on the specific growth rate was calibrated to all data. This model shows that the effect of solution Zn on specific growth rate (ErC50) was statistically unaffected by cell P quota. In contrast, this model predicts that the EbC10 (i.e. EC10 based on cell numbers) varies with P supply because cell P depends on external P and Zn. Moreover, scenario analysis predicts even contrasting trends of the EbC10 with increasing P supply depending on the duration of the growth assay and the P supply scenario. Our data at two experimental scenarios and the prediction under various relevant scenarios suggest a weaker effect of secondary stress factor (Zn) when nutrient deficiency (first stress factor) is prevailing. PMID- 26851571 TI - Developmental alterations and endocrine-disruptive responses in farmed Nile crocodiles (Crocodylus niloticus) exposed to contaminants from the Crocodile River, South Africa. AB - In the present study, the developmental (including fertility) and endocrine disruptive effects in relation to chemical burden in male and female Nile crocodiles (Crocodylus niloticus), from a commercial crocodile farm in the Brits district, South Africa, exposed to various anthropogenic aquatic contaminants from the natural environment was investigated. Hepatic transcript levels for vitellogenin (Vtg), zona pellucida (ZP) and ERalpha (also in gonads) were analyzed using real-time PCR. Plasma estradiol-17beta (E2), testosterone (T) and 11-ketotestosterone (11-KT) were analyzed using enzyme immunoassay. Gonadal aromatase and hepatic testosterone metabolism (6beta-hydroxylase (6beta-OHase)) were analyzed using biochemical methods. Overall, there is high and abnormal number (%) of infertile and banded eggs during the studied reproductive seasons, showing up to 57 and 34% of infertile eggs in the 2009/2010 and 2013/2014 seasons, respectively. In addition, the percentage of banded eggs ranged between 10 and 19% during the period of 2009-2014 seasons. While hepatic ERalpha, Vtg, ZP mRNA and testosterone 6beta-OHase, were equally expressed in female and male crocodiles, gonadal ERalpha mRNA and aromatase activity were significantly higher in females compared to male crocodiles. On the other hand, plasma T and 11-KT levels were significantly higher in males, compared to female crocodiles. Principal component analysis (PCA) produced significant grouping that revealed correlative relationships between reproductive/endocrine-disruptive variables and liver contaminant burden, that further relates to measured contaminants in the natural environment. The overall results suggest that these captive pre-slaughter farm crocodiles exhibited responses to anthropogenic aquatic contaminants with potentially relevant consequences on key reproductive and endocrine pathways and these responses may be established as relevant species endocrine disruptor biomarkers of exposure and effects in this threatened species. PMID- 26851572 TI - Characterization of a multifunctional caffeoyl-CoA O-methyltransferase activated in grape berries upon drought stress. AB - Drought stress affects anthocyanin accumulation and modification in vegetative and reproductive plant tissues. Anthocyanins are the most abundant flavonoids in grape (Vitis vinifera L.) coloured berry genotypes and are essential markers of grape winemaking quality. They are mostly mono- and di-methylated, such modifications increase their stability and improve berry quality for winemaking. Anthocyanin methylation in grape berries is induced by drought stress. A few caffeoyl-CoA O-methyltransferases (CCoAOMTs) active on anthocyanins have been described in grape. However, no drought-activated O-methyltransferases have been described in grape berries yet. In this study, we characterized VvCCoAOMT, a grapevine gene known to induce methylation of CoA esters in cultured grape cells. Transcript accumulation of VvCCoAOMT was detected in berry skins, and increased during berry ripening on the plant, and in cultured berries treated with ABA, concomitantly with accumulation of methylated anthocyanins, suggesting that anthocyanins may be substrates of this enzyme. Contrary as previously observed in cell cultures, biotic stress (Botrytis cinerea inoculation) did not affect VvCCoAOMT gene expression in leaves or berries, while drought stress increased VvCCoAOMT transcript in berries. The recombinant VvCCoAOMT protein showed in vitro methylating activity on cyanidin 3-O-glucoside. We conclude that VvCCoAOMT is a multifunctional O-methyltransferase that may contribute to anthocyanin methylation activity in grape berries, in particular under drought stress conditions. PMID- 26851573 TI - Monoamine oxidase and agitation in psychiatric patients. AB - Subjects with schizophrenia or conduct disorder display a lifelong pattern of antisocial, aggressive and violent behavior and agitation. Monoamine oxidase (MAO) is an enzyme involved in the degradation of various monoamine neurotransmitters and neuromodulators and therefore has a role in various psychiatric and neurodegenerative disorders and pathological behaviors. Platelet MAO-B activity has been associated with psychopathy- and aggression-related personality traits, while variants of the MAOA and MAOB genes have been associated with diverse clinical phenotypes, including aggressiveness, antisocial problems and violent delinquency. The aim of the study was to evaluate the association of platelet MAO-B activity, MAOB rs1799836 polymorphism and MAOA uVNTR polymorphism with severe agitation in 363 subjects with schizophrenia and conduct disorder. The results demonstrated significant association of severe agitation and smoking, but not diagnosis or age, with platelet MAO-B activity. Higher platelet MAO-B activity was found in subjects with severe agitation compared to non-agitated subjects. Platelet MAO-B activity was not associated with MAOB rs1799836 polymorphism. These results suggested the association between increased platelet MAO-B activity and severe agitation. No significant association was found between severe agitation and MAOA uVNTR or MAOB rs1799836 polymorphism, revealing that these individual polymorphisms in MAO genes are not related to severe agitation in subjects with schizophrenia and conduct disorder. As our study included 363 homogenous Caucasian male subjects, our data showing this negative genetic association will be a useful addition to future meta analyses. PMID- 26851574 TI - Weight stigma and eating behaviours in elementary school children: A prospective population-based study. AB - The relevance of weight stigma as an important factor in disordered eating has been supported by research. However, because most of the studies were cross sectional and focussed on older children, the causal relationships could not be fully determined in childhood. The current study explores the role of weight stigma in body dissatisfaction and eating behaviours. The sample consisted of 773 girls and 713 boys, aged 6-11 years, who completed surveys assessing weight stigma experiences, body dissatisfaction and eating behaviours at two points of measurement, approximately one year apart. The children's external and disordered eating was rated via parental questionnaires. As expected, the pattern of the associations between weight status, weight stigma, body dissatisfaction and eating behaviours differed by gender. Experience of weight stigma in girls led to external and restrained eating one year later, whereas in boys no such association was observed. Body dissatisfaction mediated the association between weight stigma and restrained eating behaviours in girls, whereas in boys, body dissatisfaction directly influenced restrained eating behaviours. However, in both girls and boys weight status predicted body dissatisfaction and disordered eating, while weight stigma did not have a direct effect on disordered eating. Results suggest that interventions involving weight stigma should be a part of eating disorder prevention programmes, and gender-specific pathways should be considered. PMID- 26851575 TI - Measuring wanting and liking from animals to humans: A systematic review. AB - Animal research has shown it is possible to want a reward that is not liked once obtained. Although these findings have elicited interest, human experiments have produced contradictory results, raising doubts about the existence of separate wanting and liking influences in human reward processing. This discrepancy could be due to inconsistences in the operationalization of these concepts. We systematically reviewed the methodologies used to assess human wanting and/or liking and found that most studies operationalized these concepts in congruency with the animal literature. Nonetheless, numerous studies operationalized wanting in similar ways to those that operationalized liking. These contradictions might be driven by a major source of confound: expected pleasantness. Expected pleasantness underlies cognitive desires and does not correspond to animal liking, a hedonic experience, or to animal wanting, which relies on affective relevance, consisting of the perception of a cue associated with a relevant reward for the organism's current physiological state. Extending the concept of affective relevance and differentiating it from expected pleasantness might improve measures of human wanting and liking. PMID- 26851576 TI - Effects of fibrillation on the wood fibers' enzymatic hydrolysis enhanced by mechanical refining. AB - The hardwood bleached kraft pulp (HBKP) fibers were pretreated by PFI mill to obtain the substrates, the effects of fibrillation on HBKP fibers' enzymatic hydrolysis was studied. The results showed that the enzymatic hydrolysis efficiency was enhanced obviously by mechanical refining. The mechanical refining alterated the fibers' characteristics such as fibrillation degree, specific surface area, swelling ability, crystallinity, fiber length and fines content. All these factors correlating to the enzymatic hydrolysis were evaluated through mathematical analysis. Among these factors, the fibrillation degree has the profoundest impact on the enzymatic hydrolysis of wood fibers. Consequently, the mechanical refining aiming for a high fibrillation degree was feasible to enhance the enzymatic hydrolysis of lignocellulosic biomass. PMID- 26851577 TI - The value of imaging in subclinical coronary artery disease. AB - Although the treatment of acute coronary syndromes (ACS) has advanced considerably, the ability to detect, predict, and prevent complications of atherosclerotic plaques, considered the main cause of ACS, remains elusive. Several imaging tools have therefore been developed to characterize morphological determinants of plaque vulnerability, defined as the propensity or probability of plaques to complicate with coronary thrombosis, able to predict patients at risk. By utilizing both intravascular and noninvasive imaging tools, indeed prospective longitudinal studies have recently provided considerable knowledge, increasing our understanding of determinants of plaque formation, progression, and instabilization. In the present review we aim at 1) critically analyzing the incremental utility of imaging tools over currently available "traditional" methods of risk stratification; 2) documenting the capacity of such modalities to monitor atherosclerosis progression and regression according to lifestyle modifications and targeted therapy; and 3) evaluating the potential clinical relevance of advanced imaging, testing whether detection of such lesions may guide therapeutic decisions and changes in treatment strategy. The current understanding of modes of progression of atherosclerotic vascular disease and the appropriate use of available diagnostic tools may already now gauge the selection of patients to be enrolled in primary and secondary prevention studies. Appropriate trials should now, however, evaluate the cost-effectiveness of an aggressive search of vulnerable plaques, favoring implementation of such diagnostic tools in daily practice. PMID- 26851578 TI - Paper-based biosensor relying on flower-like reduced graphene guided enzymatically deposition of polyaniline for Pb(2+) detection. AB - A multi-amplified paper-based electrochemical strategy using Pb(2+) dependent DNAzyme as the recognition unit for Pb(2+) detection was developed. In this work, flower-like reduced graphene (FrGO) was prepared utilizing flower-like ZnO as template, which was first one step grown on the gold nanoparticles modified paper working electrode (Au-PWE). After being treated with acid and then modified with Au, a novel sensor platform named Au/FrGO/Au-PWE with large specific surface area and good electrical conductivity was fabricated. The Mn2O3 nanoparticle-assembled hierarchical hollow spheres (H-Mn2O3) was served as nanocarrier to immobilize GOx, HRP and signal strand (S3), resulting to the formation of S3/H-Mn2O3/HRP/GOx bioconjugations. In the presence of Pb(2+), the DNAzyme (S1) was activated and the substrate strand (S2) was cleaved. After the incubation with S3/H Mn2O3/HRP/GOx in 0.1M HAc-NaAc solution (pH 4.3) containing 30 mM aniline and 15 mM glucose, a readily measurable "turn-on" electrochemical signal could be measured. On the basis of the signal amplification strategy of Au/FrGO/Au-PWE sensing platform and S3/H-Mn2O3/HRP/GOx bioconjugations, the developed biosensor exhibited a good linear response toward over a wide range of concentration from 0.005 to 2000 nM. PMID- 26851579 TI - Label-free immunosensor based on one-step electrodeposition of chitosan-gold nanoparticles biocompatible film on Au microelectrode for determination of aflatoxin B1 in maize. AB - Gold nanoparticles (AuNPs) embedded in chitosan (CHI) film, well-dispersed and smaller in size (about 10 nm), were fabricated by one-step electrodeposion on Au microelectrode in solution containing chitosan and chloride trihydrate. The nano structure CHI-AuNPs composite film offers abundant amine groups, good conductivity, excellent biocompatibility and stability for antibody immobilization. The combination of aflatoxin B1 (AFB1) with immobilized antibody introduces a barrier to electron transfer, resulting in current decreasement. The morphologies and characterizations of modified microelectrodes were investigated by scanning electron microscope (SEM), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and Fourier transform infrared spectroscopy (FT-IR). The proposed non-enzyme and label-free immunosensor exhibited high sensitive amperometric response to AFB1 concentration in two linear ranges of 0.1 to 1 ng mL(-1) and 1 to 30 ng mL(-1), with the detection limit of 0.06 ng mL(-1) (S/N=3). The immunoassay was also applied for analysis of maize samples spiked with AFB1. Considering the sample extraction procedure, the linear range and limit of detection were assessed to be 1.6-16 ng mL(-1) and 0.19 ng mL(-1) respectively. The simple method showed good fabrication controllability and reproducibility for immunosensor design. PMID- 26851581 TI - Fluorescence enhancement aided by metal ion displacement. AB - Immunosensors are one of the most common platform used in clinical laboratories, in particular the class based on Enzyme Linked Fluorescent Assays (ELFA) takes advantage of the amplification step of the enzyme, usually the alkaline phosphatase, that catalyzes the hydrolysis of a fluorescent substrate leading it to fluoresce. Anyway, they suffer in sensitivity if compared to molecular diagnostic or more modern in vitro diagnostic devices. In our work, a simple and effective mechanism to enhance the fluorescent signal, and hence the sensitivity of the system, is presented. It is based on the metal ion displacement principle in which a second fluorophore, in our case Calcein Blue, quenched by a cobalt ion is add to the first one (4-MUP), and, in presence of inorganic phosphate, it will be progressively activated by the inorganic phosphate itself leading to the metal displacement. In this way Calcein Blue, newly free to fluoresce, contributes to global fluorescent signal generated by 4-MU. We have tested our proof of principle on a currently used immunoanalyzer, that is VIDAS(r) system (bioMerieux, Marcy l'Etoile, France) obtaining a fluorescence enhancement of about 50% for each concentration of hydrolyzed 4-MUP tested. PMID- 26851580 TI - Electrical response of a B lymphoma cell line latently infected with Kaposi's sarcoma herpesvirus. AB - Certain viruses, such as herpesviruses, are capable of persistent and latent infection of host cells. Distinguishing and separating live, latently infected cells from uninfected cells is not easily attainable using current approaches. The ability to perform such separation would greatly enhance the ability to study primary, infected cells and potentially enable elimination of latently infected cells from the host. Here, the dielectrophoretic response of B cells infected with Kaposi's sarcoma-associated herpesvirus (KSHV) were investigated and compared to uninfected B cells. We evaluated the effect of applied voltage, signal frequency, and flow rate of the sample on the cell capture efficiency. We achieved 37.1% +/- 8.5% difference in capture efficiencies between latently KSHV infected and uninfected BJAB B lymphoma cells at the chip operational conditions of 1V, 50 kHz and 0.02 MUl/min sample flow rate. Our results show that latently infected B lymphoma cells demonstrated significantly different electrical response compared to uninfected B cells and DEP-based microchips can be potentially used for sorting latently infected cells based on their electrical properties. PMID- 26851582 TI - One-step green synthetic approach for the preparation of multicolor emitting copper nanoclusters and their applications in chemical species sensing and bioimaging. AB - One-step green microwave synthetic approach was developed for the synthesis of copper nanoclusters (Cu NCs) and used as a fluorescent probe for the sensitive detection of thiram and paraquat in water and food samples. Unexpectedly, the prepared Cu NCs exhibited strong orange fluorescence and showed emission peak at 600 nm, respectively. Under optimized conditions, the quenching of Cu NCs emission peak at 600 nm was linearly proportional to thiram and paraquat concentrations in the ranges from 0.5 to 1000 uM, and from 0.2 to 1000 uM, with detection limits of 70 nM and 49 nM, respectively. In addition, bioimaging studies against Bacillus subtilis through confocal fluorescence microscopy indicated that Cu NCs showed strong blue and green fluorescence signals, good permeability and minimum toxicity against the various bacteria species, which demonstrates their potential feasibility for chemical species sensing and bioimaging applications. PMID- 26851584 TI - Nanostructured SERS-electrochemical biosensors for testing of anticancer drug interactions with DNA. AB - Widely used anti-cancer treatments involving chemotherapeutic drugs result in cancer cell damage due to their strong interaction with DNA. In this work, we have developed laboratory biosensors for screening chemotherapeutic drugs and to aid in the assessment of DNA modification/damage caused by these drugs. The sensors utilize surface-enhanced Raman scattering (SERS) spectroscopy and electrochemical methods to monitor sensory film modification and observe the drug DNA reactivity. The self-assembled monolayer protected gold-disk electrode (AuDE) was coated with a reduced graphene oxide (rGO), decorated with plasmonic gold coated Fe2Ni@Au magnetic nanoparticles functionalized with double-stranded DNA (dsDNA), a sequence of the breast cancer gene BRCA1. The nanobiosensors AuDE/SAM/rGO/Fe2Ni@Au/dsDNA were then subjected to the action of a model chemotherapeutic drug, doxorubicin (DOX), to assess the DNA modification and its dose dependence. The designed novel nanobiosensors offer SERS/electrochemical transduction, enabling chemically specific and highly sensitive analytical signals generation. The SERS measurements have corroborated the DOX intercalation into the DNA duplex whereas the electrochemical scans have indicated that the DNA modification by DOX proceeds in a concentration dependent manner, with limit of detection LOD=8 ug/mL (S/N=3), with semilog linearity over 3 orders of magnitude. These new biosensors are sensitive to agents that interact with DNA and facilitate the analysis of functional groups for determination of the binding mode. The proposed nanobiosensors can be applied in the first stage of the drug development for testing the interactions of new drugs with DNA before the drug efficacy can be assessed in more expensive testing in vitro and in vivo. PMID- 26851583 TI - Fenton reaction-based colorimetric immunoassay for sensitive detection of brevetoxin B. AB - We designed a new colorimetric immunoassay for sensitive monitoring of brevetoxin B (BTB) using enzyme-controlled Fenton reaction with a high-resolution 3,3',5,5' tetramethylbenzidine (TMB)-based visual colored system. Upon addition of hydrogen peroxide (H2O2), the equivalent iron(II) could be first converted into iron(III) and free hydroxyl radical (*OH) via the classical Fenton reaction. Then the as produced iron(III) and *OH could cause a perceptible change from colorless to blue with the increasing H2O2 concentration in the presence of TMB. Based on Fenton reaction-triggered visual colored system, a novel competitive-type colorimetric enzyme immunoassay was developed for the quantitative screening of target BTB on the bovine serum albumin-BTB-modified magnetic bead using glucose oxidase/anti-BTB antibody-labeled gold nanoparticle as the signal-transduction tag. Upon target BTB introduction, the analyte competed with the conjugated BTB on the magnetic bead for anti-BTB antibody on gold nanoparticle. The carried glucose oxidase with the gold nanoparticle could implement the oxidation of glucose to produce H2O2, and the generated H2O2 promoted the above-mentioned Fenton reaction for color development. Under the optimal conditions, the absorbance decreased with the increasing target BTB in the range from 0.1 to 150 ng kg(-1) with a low detection limit (LOD) of 0.076 ng kg(-1). The LOD was 500 fold lower than that of commercialized Abraxis BTB ELISA kit. Non-specific adsorption was not observed. The precision, reproducibility and specificity were acceptable. Finally, the method accuracy was also validated for monitoring spiked seafood samples, giving results well matched with the referenced brevetoxin ELISA kit. PMID- 26851585 TI - Practical, highly sensitive, and regenerable evanescent-wave biosensor for detection of Hg(2+) and Pb(2+) in water. AB - A "turn-on" evanescent-wave fiber biosensor based on functional nucleic acids was developed for on-site detection of Hg(2+) and Pb(2+) in environmental water samples. A two-step strategy was conducted to take advantage of the rapid binding of T-T mismatches with Hg(2+) and the cleavage of a substrate by 8-17 DNAzyme with Pb(2+) in solution, as well as sensitive DNA detection on a liquid-solid interface based on evanescent wave. The biosensor demonstrated high sensitivity (with a detection limit of 22 pM for Hg(2+) and 20 nM for Pb(2+)) and selectivity without any signal amplification, rapid detection (within 13 min per test), low cost (10-20 Chinese yuan per sample), and multiple-cycle regeneration (at least 18 times). The method was also successfully applied on Hg(2+) and Pb(2+) detection in real environmental water samples. PMID- 26851587 TI - Identification and molecular characterization of border disease virus (BDV) from sheep in India. AB - Pestiviruses isolated from sheep and goats in India thus far have been bovine viral diarrhoea virus 1 (BVDV-1) or BVDV-2. During routine genetic typing of pestiviruses in the years 2009-10, border disease virus (BDV) was detected in eight Indian sheep of a flock showing clinical signs of BD by real time RT-PCR. All the samples yielded positive virus isolates in cell culture but were found negative by a BVDV antigen ELISA. A representative BDV isolate was characterized at genetic and antigenic level. Phylogenetic analysis carried out in 5'-UTR, N(pro) and E2 regions of genome typed the Indian BDV isolate as BDV-3. A more detailed analysis in N(pro) and entire region coding structural proteins showed that the N(pro) (168), C (100 aa), E(rns) (227 aa), E1 (195 aa) and E2 (373 aa) proteins were of size characteristic for BDV reference strain X818. Antigenic differences were evident between the BDV-3 isolate and previously reported BDV-1, BDV-5 and BDV-7 strains. Although origin of BDV-3 in India is not clear, the results reflect probable introduction through trade in sheep between India and other countries or BDV-3 may be more widely distributed. Additionally, this study suggests that for diagnosis of BDV infection, the commercial BVDV Ag-ELISA should be used with caution. This is the first identification of BDV in sheep in India which highlights the need for continued pestivirus surveillance and assessing its impact on sheep and goat production. PMID- 26851586 TI - Nano-biosensors to detect beta-amyloid for Alzheimer's disease management. AB - Beta-amyloid (beta-A) peptides are potential biomarkers to monitor Alzheimer's diseases (AD) for diagnostic purposes. Increased beta-A level is neurotoxic and induces oxidative stress in brain resulting in neurodegeneration and causes dementia. As of now, no sensitive and inexpensive method is available for beta-A detection under physiological and pathological conditions. Although, available methods such as neuroimaging, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) detect beta-A, but they are not yet extended at point-of-care (POC) due to sophisticated equipments, need of high expertize, complicated operations, and challenge of low detection limit. Recently, beta-A antibody based electrochemical immuno-sensing approach has been explored to detect beta-A at pM levels within 30-40 min compared to 6-8h of ELISA test. The introduction of nano-enabling electrochemical sensing technology could enable rapid detection of beta-A at POC and may facilitate fast personalized health care delivery. This review explores recent advancements in nano-enabling electrochemical beta-A sensing technologies towards POC application to AD management. These analytical tools can serve as an analytical tool for AD management program to obtain bio-informatics needed to optimize therapeutics for neurodegenerative diseases diagnosis management. PMID- 26851588 TI - Potential novel markers to discriminate between active and latent tuberculosis infection in Chinese individuals. AB - Latent tuberculosis infection (LTBI) constitutes the main reservoir for reactivation tuberculosis. The finding of potential biomarkers for differentiating between TB and LTBI is very necessary. In this study, the immunological characteristics and potential diagnostic utility of Rv2029c, Rv2628 and Rv1813c proteins were assessed. These three proteins stimulated PBMCs from ELISPOT-positive LTBI subjects produced higher levels of IFN-gamma in comparison with TB patients and ELISPOT-negative healthy subjects (p<0.05). BCG vaccination and non-TB respiratory disease had little influence on the immunological responses of Rv2029c and Rv2628 proteins (p>0.05). The LTBI diagnostic performance of Rv2029c was higher than Rv2628 and Rv1813c by ROC evaluation. But Rv2628 had much higher specificity than Rv2029c in active TB patients and uninfected healthy subjects. The IgG level against Rv1813c was higher in the TB group than in LTBI and uninfected healthy subjects (p<0.05). These results suggest that T cell response to Rv2628 and antibody against Rv1813c might be applicable as biomarkers to distinguish TB from LTBI and uninfected individuals. PMID- 26851589 TI - Multiple etiologies of equine recurrent uveitis--A natural model for human autoimmune uveitis: A brief review. AB - Equine recurrent uveitis (ERU) has various etiologies, with Leptospira infection and genetic predisposition being the leading risk factors. Regardless of etiology, expression of ocular proteins associated with maintenance of the blood ocular barrier is impaired in ERU. The recurring-remitting cycle of ERU repeatedly disrupts the blood-ocular barrier, allowing the previously immune privileged ocular environment to become the site of a progressive local autoimmune pathology that ultimately results in tissue destruction and vision loss. The immune-mediated process involves humoral and cellular mechanisms. Intraocular antibodies either produced in the eye or that leak through the blood ocular barrier, are often present at higher levels than in serum and react with antigens in ocular tissue of horses with ERU. Ocular infiltration of auto aggressive lymphocytes occurs with each uveitis episode and is the most crucial contributor to inflammation and eye damage. Recurring uveitis episodes may be initiated when epitopes of an ocular antigen become visible to the immune system (intramolecular spreading) or another autoantigen (intermolecular spreading), resulting in a new inflammatory reaction. PMID- 26851590 TI - Coagulase-positive Staphylococcus isolated from wildlife: Identification, molecular characterization and evaluation of resistance profiles with focus on a methicillin-resistant strain. AB - The aim of the study was molecular analysis of coagulase-positive isolates of Staphylococcus bacteria obtained from wild animals and evaluation of their resistance to antimicrobial agents. A total of 76 rectal swabs were taken from wild animals. The species of the Staphylococcus isolates was determined by MALDI TOF MS, susceptibility to antimicrobials was evaluated by phenotypic and molecular methods, epidemiological analysis (ADSRRS-fingerprinting) was also carried out. MRSA isolate was typed by MLST and spa-typing. The animals tested, were carriers (n=38) of coagulase-positive Staphylococcus (S. aureus, S. pseudintermedius and S. delphini B). Analyzed isolates were resistant to 1 or 2 antimicrobials, which was confirmed by the presence of genes (blaZ, ermA, ermB, msrA, tetK and tetM). A multi-drug resistant and methicillin-resistant isolate of S. aureus was obtained as well (MRSA, ST8, t1635, PVL-positive and ACME negative). The ADSRRS-fingerprinting method enabled interspecific and intraspecific differentiation of coagulase-positive Staphylococcus isolates, revealing a certain degree of correlation between the species of the isolate, and the degree of similarity between the isolates. The presence of resistance genes in 13% (5/38) of the isolates obtained from wild animals, including one methicillin-resistant isolate, is relatively small in comparison to the degree of colonization by resistant strains in humans, livestock or pets. Nevertheless, due to the possibility of contact between wild animals, domestic animals and humans, transmission of resistant strains is possible, as suggested by our isolation of a MRSA strain typed as ST8 and specific spa type t1635, which had previously been isolated exclusively from humans. PMID- 26851591 TI - One Health in food safety and security education: A curricular framework. AB - The challenges of producing and distributing the food necessary to feed an anticipated 9 billion people in developed and developing societies by 2050 without destroying Earth's finite soil and water resources present extremely complex problems that lack simple solutions. The ability of modern societies to adequately address these and other food-related problems will require an educated workforce trained not only in traditional food safety, security, and public health, but also in other areas including food production, sustainable practices, and ecosystem health. To help address the need for such an educated workforce, a curricular framework was developed to assist those tasked with designing education and training for future food systems workers. One sentence summary: A curricular framework for education and training in food safety and security was developed that incorporates One Health concepts. PMID- 26851592 TI - Is the microagglutination test (MAT) good for predicting the infecting serogroup for leptospirosis in Brazil? AB - Leptospirosis is a zoonotic infection caused by pathogenic members of the genus Leptospira spp. Knowledge of the prevalent serovars and their maintenance hosts is essential to understand the disease. The aim of this study was to evaluate the ability of serology by the microscopic agglutination test (MAT) to predict the serogroups compared with results of identification of leptospires in Sao Paulo, Brazil. MAT correctly assigned the serogroup of the infecting isolate in 49/52 cases (94.23%). The serogroup Icterohaemorrhagiae was the predominant serogroup (88.46%). This study showed the usefulness of the MAT to correctly identify the infecting serogroup with a good overall agreement between the serologically identified infecting serogroup and by identification of the isolate and can be used in epidemiological surveys in Sao Paulo. However, it should be complemented by the identification of Leptospira isolates. PMID- 26851593 TI - Occurrence and antimicrobial resistance of emergent Arcobacter spp. isolated from cattle and sheep in Iran. AB - This study is conducted to determine the occurrence and antimicrobial resistance of Arcobacter spp. isolated from clinically healthy food animals. A total of 308 samples from cattle (200) and sheep (108) were collected from Shiraz slaughterhouse, southern Iran to investigate the presence of the important Arcobacter spp. using cultivation and Polymerase Chain Reaction (PCR) methods. Antimicrobial susceptibility of Arcobacter isolates was determined for 18 antibiotics using disk diffusion method. Among 308 samples, 27 (8.7%) and 44 (14.28%) were positive for the presence of Arcobacter species with cultivation and PCR procedures, respectively. The predominant species was A. butzleri in both cattle (58.33%) and sheep (55%). In addition, concurrent incidence of the species was observed in 25% of the positive samples. All Arcobacter isolates were resistant to rifampicin, vancomycin, ceftriaxone, trimethoprim and cephalothin. The isolates showed high susceptibility to tetracycline, oxytetracycline, erythromycin, ciprofloxacin, kanamycin, amikacin, gentamicin and enrofloxacin. No significant difference among cattle and sheep isolates in resistance pattern was observed. The results indicate that cattle and sheep are significant intestinal carriers for Arcobacter spp. Moreover, tetracycline and aminoglycosides showed great effects on Arcobacter species in antibiogram test and can be used for treatment of human Arcobacter infections. PMID- 26851594 TI - Immunological evaluation of an rsmD-like rRNA methyltransferase from Wolbachia endosymbiont of Brugia malayi. AB - Wolbachia is a wonderful anti-filarial target with many of its enzymes and surface proteins (WSPs) representing potential drug targets and vaccine candidates. Here we report on the immunologic response of a drug target, rsmD like rRNA methyltransferase from Wolbachia endosymbiont of Brugia malayi. The recombinant protein generated both humoral and cell-mediated response in BALB/c mice but compromised its immunity. The humoral response was transient and endured barely for six months in mice with or without B. Malayi challenge. In splenocytes of mice, the key humoral immunity mediating cytokine IL4 was lowered (IL4?) while IFNgamma, the major cytokine mediating cellular immunity was decreased along with upregulation of IL10 cytokine (IFNgamma?, IL10?). The finding here indicates that the enzyme has low immunogenicity and triggers lowering of cytokine level in BALB/c mice. Interestingly the overall immune profile can be summed up with equivalent response generated by WSP or whole Wolbachia. PMID- 26851595 TI - Occurrence of non-O157 Shiga toxin-producing Escherichia coli in two commercial swine farms in the Eastern Cape Province, South Africa. AB - Shiga toxin-producing Escherichia coli (STEC) is one of the most significant causes of food-borne infections capable of causing serious health complications in humans. Even though ruminants are known to be the major reservoirs of STEC, other non-ruminant food producing animals may also harbour pathogenic E. coli strains. In this study, we investigated the prevalence of E. coli serogroups O26, O111, O121, O145, and O157 and their associated virulence genes (stx1, stx2, eae, and ehxA) in swine faecal samples obtained from the two major commercial farms located in the Nkonkobe Municipality, Eastern Cape, South Africa. The proportions of serogroups detected were O26; 35 (7%), O145; 14 (2.8%), and O157:H7; 43 (8.6%) of the total animals sampled. Out of the 500 animals sampled, 22 isolates of E. coli (1.4%) tested positive for the stx2 gene, and 7 of these isolates belonged to E. coli O26 serogroup, while the remaining 15 most likely belonged to serogroups untargeted in this study. Other virulence genes (stx1, eae, and ehxA) that we screened for were not detected. These findings reveal that pigs within the Eastern Cape Province of South Africa can harbour Shiga toxin-producing E. coli. PMID- 26851596 TI - A role for Toll-like receptor 4 in the host response to the lung infection of Yersinia pseudotuberculosis in mice. AB - Although a Yersinia pseudotuberculosis (Yptb) lung infection model has been developed to study Y. pestis pathogenesis, it is still necessary to establish a new animal model to mimic the pathophysiological features induced by Y. pestis infection. Here, we provide a new lung infection model using the Yptb strain, IP2777, which displayed rapid spread of bacteria to the liver, spleen, and blood. In addition, we examined whether TLR4 is involved in Yptb-induced pathogenesis in the lung infection model of mice we generated. Following lung infection of WT and TLR4-deficient mice with the Yptb strain IP2777, the survival rate, bacterial colonization, histopathology, and level of cytokines and chemokines in the lung, spleen, liver, and blood were analyzed. TLR4-deficient mice had a lower survival rate than WT mice in response to Yptb lung infection. Although the bacterial colonization and pathology of the lung were comparable between WT and TLR4 deficient mice, those of the spleen and liver were more severe in TLR4-deficient mice. In addition, the levels of TNF-alpha and CXCL2 in the liver and IL-6 and CXCL2 in the blood were higher in TLR4-deficient mice than in WT mice. Our results demonstrate that TLR4 is necessary for optimal host protection against Yptb lung infection and TLR4-deficient mice may serve as a better genetic model of Yptb infection for mimicking Y. pestis infection. PMID- 26851597 TI - The glucagon-like peptide 1 (GLP) receptor as a therapeutic target in Parkinson's disease: mechanisms of action. AB - Growing evidence suggests that agonists of the glucagon-like peptide 1 (GLP-1) receptor provide neuroprotection across a range of experimental models of Parkinson's disease (PD) and, recently, a small proof-of-concept, open-label human trial of exenatide in the treatment moderate severity PD appeared to show persistent improvements in motor and cognitive function. The underlying mechanisms of action remain unclear, but as evidence for the potential use of GLP 1 agonists in treating several neurodegenerative disease mounts, and with several clinical trials of GLP-1 analogues in PD and Alzheimer's disease (AD) currently underway, here we review the molecular mechanisms underlying the neuroprotective effects of GLP-1 analogues in the laboratory and their potential therapeutic utility with particular relevance to PD and PD dementia (PDD). PMID- 26851598 TI - Surgical treatment of deep infiltrating rectal endometriosis: in favor of less aggressive surgery. AB - Deep infiltrating endometriosis of the rectum is a severe disease concerning young women of reproductive age. Because it is a benign condition, aggressive surgical treatment and subsequent complications are not always accepted by young patients. Two surgical approaches exist: the radical approach, employing colorectal resection; and the conservative approach, based on rectal shaving or full-thickness disc excision. At present, the majority of patients with rectal endometriosis worldwide are managed by the radical approach. Conversely, as high as 66% of patients with colorectal endometriosis can be managed by either rectal shaving or full-thickness disc excision. Most arguments that used to support the large use of the radical approach may now be disputed. The presumed higher risk of recurrence related to conservative surgery can be balanced by a supposed higher risk of postoperative bowel dysfunction related to the radical approach. Bowel occult microscopic endometriosis renders debatable the hypothesis that more aggressive surgery can definitively cure endometriosis. Although most surgeons consider that radical surgery is unavoidable in patients with rectal nodules responsible for digestive stenosis, conservative surgery can be successfully performed in a majority of cases. In multifocal bowel endometriosis, multiple conservative procedures may be proposed, provided that the nodules are separated by segments of healthy bowel of longer than 5 cm. Attempting conservation of a maximum length of rectum may reduce the risk of postoperative anterior rectal resection syndrome and subsequent debilitating bowel dysfunction and impaired quality of life. Promotion of less aggressive surgery with an aim to better spare organ function has become a general tendency in both oncologic and benign pathologies; thus the management of deep colorectal endometriosis should logically be concerned, too. PMID- 26851599 TI - Nonantimuscarinic treatment for overactive bladder: a systematic review. AB - The purpose of the study was to determine the efficacy and safety of nonantimuscarinic treatments for overactive bladder. Medline, Cochrane, and other databases (inception to April 2, 2014) were used. We included any study design in which there were 2 arms and an n > 100, if at least 1 of the arms was a nonantimuscarinic therapy or any comparative trial, regardless of number, if at least 2 arms were nonantimuscarinic therapies for overactive bladder. Eleven reviewers double-screened citations and extracted eligible studies for study: population, intervention, outcome, effects on outcome categories, and quality. The body of evidence for categories of interventions were summarized and assessed for strength. Ninety-nine comparative studies met inclusion criteria. Interventions effective to improve subjective overactive bladder symptoms include exercise with heat and steam generating sheets (1 study), diaphragmatic (1 study), deep abdominal (1 study), and pelvic floor muscle training exercises (2 studies). Pelvic floor exercises are more effective in subjective and objective outcomes with biofeedback or verbal feedback. Weight loss with diet and exercise, caffeine reduction, 25-50% reduction in fluid intake, and pelvic floor muscle exercises with verbal instruction and or biofeedback were all efficacious. Botulinum toxin A improves urge incontinence episodes, urgency, frequency, quality of life, nocturia, and urodynamic testing parameters. Acupuncture improves quality of life and urodynamic testing parameters. Extracorporeal magnetic stimulation improves urodynamic parameters. Mirabegron improves daily incontinence episodes, nocturia, number of daily voids, and urine volume per void, whereas solabegron improves daily incontinence episodes. Short-term posterior tibial nerve stimulation is more efficacious than pelvic floor muscle training exercises and behavioral therapy for improving: urgency, urinary incontinence episodes, daily voids, volume per void, and overall quality of life. Sacral neuromodulation is more efficacious than antimuscarinic treatment for subjective improvement of overactive bladder and quality of life. Transvaginal electrical stimulation demonstrates subjective improvement in overactive bladder symptoms and urodynamic parameters. Multiple therapies, including physical therapy, behavioral therapy, botulinum toxin A, acupuncture, magnetic stimulation, mirabegron, posterior tibial nerve stimulation, sacral neuromodulation, and transvaginal electrical stimulation, are efficacious in the treatment of overactive bladder. PMID- 26851600 TI - The association between Myers-Briggs Type Indicator and Psychiatry as the specialty choice. AB - OBJECTIVE: The purpose of this pilot study is to examine the association between Myers-Briggs Type Indicator (MBTI) and prospective psychiatry residents. METHODS: Forty-six American medical schools were contacted and asked to participate in this study. Data were collected and an aggregated list was compiled that included the following information: date of MBTI administration, academic year, MBTI form/version, residency match information and student demographic information. The data includes 835 American medical students who completed the MBTI survey and matched into a residency training program in the United States. All analyses were performed using R 3.1.2. RESULTS: The probability of an introvert matching to a psychiatry residency is no different than that of an extravert (p= 0.30). The probability of an intuitive individual matching to a psychiatry residency is no different than that of a sensing type (p=0.20). The probability of a feeling type matching to a psychiatry residency is no different than that of a thinking type (p= 0.50). The probability of a perceiving type matching to a psychiatry residency is no different than that of a judging type (p= 0.60). CONCLUSIONS: Further analyses may elicit more accurate information regarding the personality profile of prospective psychiatry residents. The improvement in communication, team dynamics, mentor-mentee relationships and reduction in workplace conflicts are possible with the awareness of MBTI personality profiles. PMID- 26851601 TI - The effects of a picosecond pulsed electric field on angiogenesis in the cervical cancer xenograft models. AB - OBJECTIVE: The application of picosecond pulsed electric field (psPEF) is a new biomedical engineering technique used in cancer therapy. However, its effects on cervical cancer angiogenesis are not clear. Therefore, the aim of the present study is to investigate the effects of psPEF on angiogenesis in cervical cancer xenograft models. METHODS: Xenograft tumors were created by subcutaneously inoculating nude mice (athymic BALB/c nu/nu mice) with HeLa cells, then were placed closely between tweezer-type plate electrodes and subjected to psPEF with a gradually increased electric field intensity (0kV/cm, 50kV/cm, 60kV/cm, 70kV/cm). The direct effect on tumor tissue was observed by hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). The changes of blood vessels and oxygen saturation (sO2) of tumors were monitored in vivo by photoacoustic tomography (PAT). The microvessel density (MVD), vascular endothelial growth factor (VEGF) and hypoxia-inducible transcription factors (HIF 1alpha and HIF-2alpha) were detected by immunohistochemical technique (IHC). Their protein expressions and gene transcription levels were evaluated using western blot (WB) and quantitative reverse transcription and polymerase chain reaction (RT-PCR). RESULTS: PsPEF induced obvious necrosis of cervical cancer tissue; with the increasing of electric field intensity, the MVD, vascular PA signal and sO2 values declined significantly. The protein expression and gene transcription levels of VEGF, HIF1alpha and HIF2alpha were significantly decreased at the same time. CONCLUSION: PsPEF exhibited dramatic anti-tumor and anti-angiogenesis effects in cervical cancer xenograft models by exerting direct effect on cancer cells and vascular endothelial cells and indirect effect on tumor angiogenesis-related factors. PMID- 26851602 TI - NMR-based metabonomics for understanding the influence of dormant female genital tuberculosis on metabolism of the human endometrium. AB - STUDY QUESTION: Does investigation of metabolic perturbations in endometrial tissue of women with dormant genital tuberculosis (GTB) during the window of implantation (WOI) assist in improving the understanding of endometrial receptivity? SUMMARY ANSWER: In dormant GTB cases significant alterations in endometrial tissue metabolites occur, largely related to energy metabolism and amino acid biosynthesis in dormant GTB cases. WHAT IS KNOWN ALREADY: As an intracellular pathogen, Mycobacterium tuberculosis strongly influences the metabolism of host cells causing metabolic dysregulation. It is also accepted that dormant GTB impairs the receptive status of the endometrium. Global metabolic profiling is useful for an understanding of disease progression and distinguishing between diseased and non-diseased groups. STUDY DESIGN, SIZE, DURATION: Endometrial tissue samples were collected from patients reporting at the tertiary infertility care center during the period September 2011-March 2013. Women having tested positive for GTB were considered as the study group (n = 24). Normal healthy women undergoing sterilization (n = 26) and unexplained infertile women with repeated IVF failure (n = 21) volunteered to participate as controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: Endometrial tissue samples were collected 6-10 days after confirmation of ovulation. PCR and BACTEC-460 culture were used for diagnosing GTB. Proton nuclear magnetic resonance (1H NMR) spectra of tissue were recorded using a 700 MHz Bruker Avance AV III spectrometer. Following phase and baseline correction of all NMR spectra by Bruker Topspin 2.1 software, spectral peak alignment of the data was performed. Multivariate analysis was applied to all spectra and individual metabolites identified and multiple correlation analysis was performed. MAIN RESULTS AND THE ROLE OF CHANCE: Leucine, isoleucine, acetate, lactate, glutamate, glutamine, methionine, lysine, creatine, glycogen, glycine, proline and choline were found to be significantly increased (P < 0.05) in endometrial tissue of women with dormant GTB compared with unexplained infertile women with repeated implantation failure. Valine, citrate, succinate and aspartate were also observed to be significantly up regulated (P < 0.01). Furthermore, a significant decrease in glucose (P < 0.05), threonine (P < 0.05), tyrosine (P < 0.01) and phenylalanine (P < 0.0001) was observed in women with dormant GTB. Pearson's correlation analysis between the expression of various endometrial receptivity markers and metabolites showed a significant negative correlation (-0.236 to -0.545, P < 0.05). Also, the metabolites were positively correlated with endometrial receptivity markers (0.207 to 0.618, P < 0.05). LIMITATIONS, REASONS FOR CAUTION: It is often difficult to diagnose dormant GTB because it tends to exist without any clinical signs or symptoms. In addition, the diagnosis of GTB by culture remains a challenge due to low detection rates and its paucibacillary nature. Testing for prostate-specific antigen or the Y chromosome in order to account for the possible influences of recent exposure to semen on endometrial metabolism would be important. WIDER IMPLICATIONS OF THE FINDINGS: The metabolic changes associated with the dormant tubercle infection are of potential relevance to clinicians for the treatment of dormant GTB-related infertility. STUDY FUNDING/COMPETING INTERESTS: Government of India, Indian Council of Medical Research. There are no conflicts of interest. PMID- 26851603 TI - Human single follicle growth in vitro from cryopreserved ovarian tissue after slow freezing or vitrification. AB - STUDY QUESTION: What is the effect of human ovarian tissue cryopreservation on single follicular development in vitro? SUMMARY ANSWER: Vitrification had a greater negative effect on growth and gene expression of human ovarian follicles when compared with fresh follicles. WHAT IS KNOWN ALREADY: For human ovarian cortex cryopreservation, the conventional option is slow freezing while more recently vitrification has been demonstrated to maintain good quality and function of ovarian tissues. STUDY DESIGN, SIZE, DURATION: Ovarian tissues were collected from 11 patients. For every patient, the ovarian cortex was divided into three samples: Fresh, slow-rate freezing (Slow) and vitrification (Vit). Tissue histology was performed and follicles were isolated for single-cell mRNA analysis and in vitro culture (IVC) in 1% alginate for 8 days. PARTICIPANTS/MATERIALS, SETTING, METHODS: Follicle morphology was assessed with hematoxylin-eosin analysis. Follicles were individually embedded in alginate (1% w/v) and cultured in vitro for 8 days. Follicle survival and growth were assessed by microscopy. Follicle viability was observed after Calcein-AM and ethidium homodimer-I (Ca-AM/EthD-I) staining. Expression of genes, including GDF9 (growth differentiation factor 9), BMP15 (bone morphogenetic protein 15) and ZP3 (zona pellucida glycoprotein 3) in oocytes and AMH (anti-Mullerian hormone), FSHR (FSH receptor), CYP11A (cholesterol side-chain cleavage cytochrome P450) and STAR (steroidogenic acute regulatory protein) in GCs, was evaluated by single-cell mRNA analysis. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 129 follicles were separated from ovarian cortex (Fresh n = 44; Slow n = 40; Vit n = 45). The percentage of damaged oocytes and granulosa cells was significantly higher in both the Slow and Vit groups, as compared with Fresh control (P< 0.05). The growth of follicles in vitro was significantly delayed in the Vit group compared with the Fresh group (P< 0.05). Both slow freezing (P< 0.05) and vitrification (P< 0.05) down-regulated the mRNA levels of ZP3 and CYP11A compared with Fresh group, while there was no significant difference between the Slow and Vit groups (P> 0.05). Vitrification also down-regulates AMH mRNA levels compared with Fresh group (P< 0.05). LIMITATIONS, REASONS FOR CAUTION: Only short-term IVC studies (8 days) are reported. Further study should be performed to examine and improve follicular development in a long-term culture system after cryopreservation. WIDER IMPLICATIONS OF THE FINDINGS: This is the first comparison of gene expression and growth of single human ovarian follicles in vitro after either slow freezing or vitrification. With the decreased gene expression and growth during IVC, damage by cryopreservation still exists and needs to be minimized during the long-term IVC of follicles in the future for eventual clinical application. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Natural Science Foundation of China (31230047, 81571386, 81471508, 31429004 and 81501247), National Natural Science Foundation of Beijing (7142166) and Mega-projects of Science Research for the 12th five-year plan (2012ba132b05). There are no conflicts of interest to declare. PMID- 26851604 TI - The direct and indirect costs associated with endometriosis: a systematic literature review. AB - STUDY QUESTION: What is the economic burden of endometriosis? SUMMARY ANSWER: The identified studies indicate that there is a significant economic burden associated with endometriosis, as observed by both direct and indirect costs. WHAT IS KNOWN ALREADY: Two previous systematic literature reviews suggested that there were considerable direct costs associated with endometriosis and there was a general lack of measurement of indirect costs. STUDY DESIGN, SIZE, DURATION: We performed a systematic literature review. MEDLINE and EMBASE databases from 2000 to 2013 were searched. The literature search was limited to human studies of patients with endometriosis. Papers in languages other than English were excluded. PARTICIPANTS/MATERIALS, SETTING, METHODS: Studies reporting direct or indirect costs among patients with endometriosis were considered for inclusion. Direct costs included inpatient, outpatient, surgery, drug and other healthcare service cost. Indirect costs were related to absenteeism and presenteeism (lost productivity at work). MAIN RESULTS AND THE ROLE OF CHANCE: After evaluating the 1396 articles in the search results, 12 primary studies that reported direct or indirect costs associated with endometriosis were identified and included in the data extraction. Three of the studies were conducted in the USA, one study each was conducted in Austria, Belgium, Brazil, Canada, Finland, Germany and Italy, and two studies included data from 10 countries. Significant variability was observed in the reviewed studies in methodology, including data source, cost components considered and study perspective. Estimates of total direct costs ranged from $1109 per patient per year in Canada to $12 118 per patient per year in the USA. Indirect costs of endometriosis ranged from $3314 per patient per year in Austria to $15 737 per patient per year in the USA. LIMITATIONS, REASONS FOR CAUTION: The studies identified in the systematic literature review varied greatly by study methodology as well as by country owing to different healthcare systems and costs of healthcare services, which contributed to large variations in the direct and indirect cost estimates. WIDER IMPLICATIONS OF THE FINDINGS: A majority of the studies we found were published after the periods covered in the prior systematic literature reviews, which provided substantial contributions to an understanding of the economic burden of endometriosis, especially in the area of indirect costs. The long-term burden of endometriosis following diagnosis is still under-studied, which is a concern given the chronic nature of the disease and the substantial recurrence of endometriosis symptoms. STUDY FUNDING/COMPETING INTERESTS: This study was funded by AbbVie, which also develops the oral GnRH antagonist elagolix (in collaboration with Neurocrine Biosciences) for the management of endometriosis and uterine fibroids. A.M.S. is an employee of AbbVie and currently owns AbbVie stocks. H.Y., E.X.D. and C.K. are employees of Analysis Group, Inc., which has received consultancy fees from AbbVie. C.W. is a Clinical Professor at the Department Obstetrics and Gynecology at Georgetown University in Washington, DC, USA and has served in a consulting role to AbbVie for this project. PMID- 26851605 TI - Effects of parent-only childhood obesity prevention programs on BMIz and body image in rural preteens. AB - This experiment compared body image (BI) and BMI changes resulting from two parent-only obesity prevention interventions aimed at 8-12 year olds. Parents in the experimental intervention attended ten face-to-face educational sessions, while parents in the minimal (control) intervention received similar mailed information. Parent-child dyads (N=150) were semi-randomly assigned to intervention groups. Children were assessed before, after, and 6 months following the interventions; children did not attend experimental intervention sessions. Child BI assessments included weight and size perception, weight management goals, body esteem, and appearance attitudes. Significant effects included small decreases in BMIz scores and overweight dissatisfaction, as well as improvements in aspects of body esteem and appearance attitudes. Some BI effects were gender specific. Decreases in overweight dissatisfaction were greater following the experimental treatment. Neither treatment reduced body size misperception. Thus, parent-only obesity prevention interventions can reduce body weight and body image concerns among rural preteens. PMID- 26851606 TI - Efficacy of tamoxifen and miltefosine combined therapy for cutaneous leishmaniasis in the murine model of infection with Leishmania amazonensis. AB - OBJECTIVES: The objective of this study was to characterize in vitro interactions and evaluate the antileishmanial activity of tamoxifen and miltefosine combinations. METHODS: Interactions between drugs were evaluated in vitro against Leishmania amazonensis promastigotes and intracellular amastigotes by a modified isobologram method. Four different drug ratios were used to calculate the FIC index (FICI) and the mean sum of FICI. Treatment of L. amazonensis-infected BALB/c mice was initiated 4 weeks post-infection. Mice were treated with the half maximal effective dose (ED50) or half the ED50 of tamoxifen and miltefosine orally for 15 days. Efficacy was evaluated by lesion growth and parasite burden measured through luciferase detection at the end of treatment and 30 days later. Characterization of growth curves and stepwise increase in drug concentrations in vitro were used to measure survival and resistance selection of parasite populations submitted to combination treatment. RESULTS: No in vitro interactions between tamoxifen and miltefosine were found. In infected mice, the combination of tamoxifen and miltefosine at doses corresponding to half the ED50 was more effective than monotherapy with either tamoxifen or miltefosine. When the ED50 was employed, the efficacy of the combination was equivalent to miltefosine monotherapy. In vitro, tamoxifen was able to retard or suppress the growth of parasites treated with miltefosine. CONCLUSIONS: In vitro and in vivo studies revealed no interaction between tamoxifen and miltefosine. Tamoxifen was able to hinder the emergence of miltefosine resistance. PMID- 26851607 TI - Steady-state pharmacokinetics of oral linezolid suspension in a premature infant with osteomyelitis. PMID- 26851608 TI - Fitness of Escherichia coli mutants with reduced susceptibility to tigecycline. AB - OBJECTIVES: The objective of this study was to determine the fitness of Escherichia coli mutants with reduced susceptibility to tigecycline after exposure to adverse conditions in vitro and in vivo. METHODS: Survival in response to low pH, bile salts, oxidative stress and human serum was examined for E. coli mutants with reduced susceptibility to tigecycline due to single mutations that caused increased efflux (marR, lon) or impaired LPS (rfaC, rfaE, lpcA). An in vitro competition assay was used to determine growth fitness defects. Competitive fitness was assessed using mouse infection models. MICs, exponential growth rates and expression levels of efflux-related genes were measured for genetically reconstructed double and triple mutants. RESULTS: The LPS mutants were 48-85-fold more susceptible to bile salts compared with the ERN mutants and the WT. As shown by in vitro competitions, the fitness reduction was 0.3%-13% for ERN mutants and ~24% for LPS mutants. During in vivo survival experiments, LPS mutants were outcompeted by the WT strain in the thigh infection model. Constructed double ERN and LPS mutants showed additive and synergistic increases in tigecycline MICs. CONCLUSIONS: Generally, reduced susceptibility to tigecycline caused a decrease in fitness under stressful in vitro and in vivo conditions with ERN mutants being fitter than LPS mutants. When combined, ERN mutations caused a synergistic increase in the MIC of tigecycline. These findings could explain why clinical resistance to tigecycline in E. coli is mainly associated with up-regulation of the AcrAB efflux system. PMID- 26851610 TI - Antimicrobial susceptibility testing of Arcobacter butzleri and Arcobacter cryaerophilus strains isolated from Belgian patients. AB - OBJECTIVES: To evaluate the feasibility of different methods for susceptibility testing of human Arcobacter isolates, to assess susceptibility to antibiotics commonly used to treat diarrhoeal illness and to obtain MIC distribution data. METHODS: One-hundred-and-six unique Arcobacter strains were collected during an epidemiological study on pathogens in gastroenteritis. Strains were identified by multiplex PCR and PCR-RFLP, and characterized by PFGE. Susceptibility to ampicillin, erythromycin, tetracycline, doxycycline, gentamicin and ciprofloxacin was determined using gradient strip and disc diffusion methodology. Optimal conditions for growth and incubation were tested. Azithromycin was tested with gradient strip diffusion on a subset of 40 strains. Sequence analysis of the quinolone resistance-determining region of gyrA was performed for a subset of 18 strains. RESULTS: Based on gradient diffusion results, most Arcobacter strains were susceptible to gentamicin (99%) and tetracycline (89%). Erythromycin (78%), ciprofloxacin (72%) and doxycycline (76%) retained moderate activity against Arcobacter spp. Only 9% of the strains were susceptible to ampicillin. Most Arcobacter butzleri strains were susceptible to ciprofloxacin (87%), whereas half of the Arcobacter cryaerophilus isolates (51%) showed high-level resistance (MIC >32 mg/L). MIC50 values were comparable for both macrolide antibiotics. Ciprofloxacin-resistant strains possessed an identical mutation in gyrA. Overall, categorical agreement between gradient and disc diffusion results was 60%. Gradient diffusion showed superior readability. CONCLUSIONS: Gradient diffusion methodology is preferred for routine susceptibility testing. Acquired resistance to fluoroquinolones was observed in A. cryaerophilus. Macrolides are not first choice empirical antibiotics for Arcobacter infections. Tetracyclines can be suggested for treatment of documented Arcobacter-related gastrointestinal infections. PMID- 26851609 TI - Correlation of different phenotypic drug susceptibility testing methods for four fluoroquinolones in Mycobacterium tuberculosis. AB - BACKGROUND: Molecular resistance testing fails to explain all fluoroquinolone resistance, with a continued need for a suitable rapid phenotypic drug susceptibility testing method. OBJECTIVE: To evaluate the optimal method for phenotypic fluoroquinolone susceptibility testing. METHODS: Using Lowenstein Jensen medium, Middlebrook 7H11 agar, BACTEC-MGIT 960 and the resazurin microtitre plate assay, we determined susceptibility to fluoroquinolones in Mycobacterium tuberculosis and investigated cross-resistance between ofloxacin, levofloxacin, moxifloxacin and gatifloxacin. We compared MICs of all four fluoroquinolones for 91 strains on Lowenstein-Jensen (as the gold standard) with their MICs in resazurin plates, and with ofloxacin susceptibility at a single concentration in MGIT and on 7H11 agar, in addition to sequencing of the gyrAB genes. RESULTS AND CONCLUSIONS: Applying a cut-off of 2 mg/L ofloxacin, 1 mg/L levofloxacin and 0.5 mg/L moxifloxacin and gatifloxacin in all methods, some discordance between solid medium and MGIT methods was observed, yet this tended to be explained by MICs around the cut-off. The high discordance between Lowenstein-Jensen (LJ) and resazurin plates suggests that the currently applied cut-offs for all fluoroquinolones in the resazurin method should decrease and minor changes in colour (from blue to purple) be considered as meaningful. High level resistance in all assays to all drugs correlated well with the presence of gyrA mutations, in support of recent findings that fluoroquinolone resistance should be tested at different concentrations, as patients with lower levels of resistance may continue to benefit from high-dose fluoroquinolone-based therapy. PMID- 26851611 TI - New in vitro and in vivo models to evaluate antibiotic efficacy in Staphylococcus aureus prosthetic vascular graft infection. AB - OBJECTIVE: Prosthetic vascular graft infection (PVGI) is an emerging disease, mostly caused by staphylococci, with limited data regarding efficacy of current antistaphylococcal agents. We aimed to assess the efficacy of different antibiotic regimens. METHODS: Six different strains of MSSA and MRSA were used. We compared results of minimal biofilm inhibitory and eradicating concentrations (MBICs and MBECs) obtained with a Calgary Biofilm Pin Lid Device (CBPD) with those yielded by an original Dacron((r))-related minimal inhibitory and eradicating concentration measure model. We then used a murine model of Staphylococcus aureus vascular prosthetic material infection to evaluate efficacy of different antibiotic regimens: vancomycin and daptomycin combined or not with rifampicin for MRSA and the same groups with cloxacillin and cloxacillin combined with rifampicin for MSSA. RESULTS: We demonstrated that classical measures of MBICs and MBECs obtained with a CPBD could overestimate the decrease in antibiotic susceptibility in material-related infections and that the nature of the support used might influence the measure of biofilm susceptibility, since results yielded by our Dacron((r))-related minimal eradicating assay were lower than those found with a plastic device. In our in vivo model, we showed that daptomycin was significantly more bactericidal than comparators for some strains of MRSA or MSSA but not for all. For the majority of strains, it was as efficient as comparators. The addition of rifampicin to daptomycin did not enhance daptomycin efficacy. CONCLUSIONS: Despite the heterogeneity of results according to bacterial strains, these innovative models represent an option to better evaluate the in vitro efficacy of antibiotics on Dacron((r))-related biofilm S. aureus infections, and to screen different antibiotic regimens in a mouse model of PVGIs. PMID- 26851612 TI - A novel paramyxean parasite, Marteilia octospora n. sp. (Cercozoa) infecting the Grooved Razor Shell clam Solen marginatus from Galicia (NW Spain). AB - Protozoan parasites of the genus Marteilia have been detected in marine bivalves and other invertebrates around the world, associated in some cases with mass mortalities. The present paper reports the characterization of the Marteilia sp. protozoan infecting the digestive gland of the Grooved Razor Shell clam (Solen marginatus) from Galicia (NW Spain), proposing a novel species in the genus: Marteilia octospora n. sp. Morphological and molecular techniques were used for the description of this parasite. Tissue imprints were essential in the study to confirm the presence of 8 spores per sporangium, a number never reported in other species from this genus. An ultrastructural study revealed that the size and number of dense granules, free in the mature sporangia, were quite different from granules in other Marteilia spp. Another morphological difference is the absence of a layer of concentric membranes found surrounding the mature spore in other species. In addition, concentric membranous structures observed in the different stages of the parasite have never been mentioned in other species of genus Marteilia. Moreover, molecular analysis of the rDNA intergenic spacer (IGS) and the internal transcribed spacer (ITS-1) showed differences with the sequences available for other Marteilia spp. PMID- 26851613 TI - An assessment of the information content of likelihood ratios derived from complex mixtures. AB - With the increasing sensitivity of DNA typing methodologies, as well as increasing awareness by law enforcement of the perceived capabilities of DNA typing, complex mixtures consisting of DNA from two or more contributors are increasingly being encountered. However, insufficient research has been conducted to characterize the ability to distinguish a true contributor (TC) from a known non-contributor (KNC) in these complex samples, and under what specific conditions. In order to investigate this question, sets of six 15-locus Caucasian genotype profiles were simulated and used to create mixtures containing 2-5 contributors. Likelihood ratios were computed for various situations, including varying numbers of contributors and unknowns in the evidence profile, as well as comparisons of the evidence profile to TCs and KNCs. This work was intended to illustrate the best-case scenario, in which all alleles from the TC were detected in the simulated evidence samples. Therefore the possibility of drop-out was not modeled in this study. The computer program DNAMIX was then used to compute LRs comparing the evidence profile to TCs and KNCs. This resulted in 140,000 LRs for each of the two scenarios. These complex mixture simulations show that, even when all alleles are detected (i.e. no drop-out), TCs can generate LRs less than 1 across a 15-locus profile. However, this outcome was rare, 7 of 140,000 replicates (0.005%), and associated only with mixtures comprising 5 contributors in which the numerator hypothesis includes one or more unknown contributors. For KNCs, LRs were found to be greater than 1 in a small number of replicates (75 of 140,000 replicates, or 0.05%). These replicates were limited to 4 and 5 person mixtures with 1 or more unknowns in the numerator. Only 5 of these 75 replicates (0.004%) yielded an LR greater than 1,000. Thus, overall, these results imply that the weight of evidence that can be derived from complex mixtures containing up to 5 contributors, under a scenario in which no drop-out is required to explain any of the contributors, is remarkably high. This is a useful benchmark result on top of which to layer the effects of additional factors, such as drop out, peak height, and other variables. PMID- 26851614 TI - For Better or Worse? Change in Service Use by Children Investigated by Child Welfare Over a Decade. AB - BACKGROUND: Children, particularly minority children, referred to child welfare because of suspected maltreatment are vulnerable and need many services. We sought to assess whether service use has improved over the past decade and whether racial-ethnic disparities in service use have decreased. METHODS: We used 2 national data sets (the National Survey of Child and Adolescent Well-Being [NSCAW] I and II) collected a decade apart to assess changes over time in health, education, mental health (MH), and dental services and overall service use. RESULTS: In NSCAW II more children were young, had lower Child Behavior Checklist (CBCL) scores, and were Hispanic. We found significant increases in dental services, a decrease in special education services, and a decrease in MH services on the bivariate level (all P < .01). A large proportion of the change in MH services occurred in school settings, but the pattern continued when examining only those services delivered outside of school. The greatest decrease occurred for children with CBCL scores <64. However, in multivariate analyses, older children, white non-Hispanic children, and children placed out of the home were significantly more likely to receive MH services. Rates of MH services controlling for CBCL scores showed no improvement over the decade, nor was there a decrease in racial and ethnic disparities. CONCLUSIONS: These data showed no change in MH services over time for children referred for child welfare evaluation, but improvement in dental services was noted. Racial and ethnic disparities persist. Decrease in MH services occurred predominantly among children whose MH symptoms were below the clinical range. PMID- 26851615 TI - Infant Sleep Location and Breastfeeding Practices in the United States, 2011 2014. AB - OBJECTIVE: To describe the prevalence of breastfeeding and sleep location practices among US mothers and the factors associated with these behaviors, including advice received regarding these practices. METHODS: A nationally representative sample of 3218 mothers who spoke English or Spanish were enrolled at a sample of 32 US birth hospitals between January 2011 and March 2014. RESULTS: Exclusive breastfeeding was reported by 30.5% of mothers, while an additional 29.5% reported partial breastfeeding. The majority of mothers, 65.5%, reported usually room sharing without bed sharing, while 20.7% reported bed sharing. Compared to mothers who room shared without bed sharing, mothers who bed shared were more likely to report exclusive breastfeeding (adjusted odds ratio 2.46, 95% confidence interval 1.76, 3.45) or partial breastfeeding (adjusted odds ratio 1.75, 95% confidence interval 1.33, 2.31). The majority of mothers reported usually room sharing without bed sharing regardless of feeding practices, including 58.2% of exclusively breastfeeding mothers and 70.0% of nonbreastfeeding mothers. Receiving advice regarding sleep location or breastfeeding increased adherence to recommendations in a dose response manner (the adjusted odds of room sharing without bed sharing and exclusive breastfeeding increased as the relevant advice score increased); however, receiving advice regarding sleep location did not affect feeding practices. CONCLUSIONS: Many mothers have not adopted the recommended infant sleep location or feeding practices. Receiving advice from multiple sources appears to promote adherence in a dose response manner. Many women are able to both breastfeed and room share without bed sharing, and advice to adhere to both of these recommendations did not decrease breastfeeding rates. PMID- 26851616 TI - Hypersexuality and couple relationships in bipolar disorder: A review. AB - BACKGROUND: Although change in sexual behavior is recognized as an integral part of bipolar disorder, most of the relevant literature on sexual issues in patients with this illness concerns medication side effects and does not differentiate bipolar disorder from other serious mental disorders. Surprisingly, little has been published on mania-induced hypersexuality and the effects of mood cycling on couple relationships. In this review, we examine the extant literature on both of these subjects and propose a framework for future research. METHODS: A search of PsycINFO and PubMed was conducted using keywords pertaining to bipolar disorder, hypersexuality and couple relationships. A total of 27 articles were selected for review. RESULTS: Despite lack of uniformity in diagnosis of bipolar disorder and no formal definition of hypersexuality, the literature points to an increased incidence of risky sexual behaviors in bipolar patients during manic episodes compared to patients with other psychiatric diagnoses. Further, it appears that bipolar patients are more similar to healthy controls than to other psychiatric patients when it comes to establishing and maintaining couple relationships. Nonetheless, the studies that examined sexuality in couples with one bipolar partner found decreased levels of sexual satisfaction associated with the diagnosis, varying levels of sexual interest across polarities, increased incidence of sexual dysfunction during depressive episodes, and disparate levels of satisfaction in general between patients and their partners. LIMITATIONS: Due to changes in diagnostic criteria over time, there is a lack of uniformity in the definition of bipolar disorder across studies. Hypersexuality is not systematically defined and therefore the construct was not consistent across studies. Some of the older articles date back more than 30 years, making them subject to the biases of sexual and gender norms that have since become outdated. Finally, the heterogeneity of the samples, which include patients with comorbid substance use as well as inpatient, outpatient, symptomatic and euthymic patients, may limit the generalizability of results. CONCLUSIONS: Although bipolar patients experience disease-specific sexual problems of mania-induced hypersexuality and specific effects of mood cycling on couple relationships, the existing literature is mostly outdated and lacks a consistent definition of hypersexuality. Novel research is needed to address sexual symptomatology in bipolar disorder within the context of current sexual, cultural and gender norms. PMID- 26851617 TI - The deterioration of driving performance over time in drivers with untreated sleep apnea. AB - Sleep apnea increases risk of driving crashes when left untreated. This study examined the driving performance decrements of untreated, undiagnosed sleep apnea drivers compared with healthy controls in a monotonous highway driving simulator task. It was hypothesized that the sleep apnea group would perform worse during a driving simulator test compared with the control group. A significant group by time interaction occurred indicating that sleep apnea participants' performance degraded more quickly over the course of the drive. In contrast with previous studies, this sleep apnea group did not include sleep disorder center patients, but rather community volunteers whose screening indicated a significant apnea/hypopnea index of 15 or greater. There may be inherent differences between patients and nonpatients with sleep apnea, as patients may have a more significant impact on their quality of life, causing them to seek treatment. Still, the results are clear that although the sleep apnea group drove similarly to the control group at the start of the drive, they are sensitive to time on task effects. These results support the need to diagnose and treat sleep apnea. PMID- 26851618 TI - Computerized "Learn-As-You-Go" classification of traumatic brain injuries using NEISS narrative data. AB - One important routine task in injury research is to effectively classify injury circumstances into user-defined categories when using narrative text. However, traditional manual processes can be time consuming, and existing batch learning systems can be difficult to utilize by novice users. This study evaluates a "Learn-As-You-Go" machine-learning program. When using this program, the user trains classification models and interactively checks on accuracy until a desired threshold is reached. We examined the narrative text of traumatic brain injuries (TBIs) in the National Electronic Injury Surveillance System (NEISS) and classified TBIs into sport and non-sport categories. Our results suggest that the DUALIST "Learn-As-You-Go" program, which features a user-friendly online interface, is effective in injury narrative classification. In our study, the time frame to classify tens of thousands of narratives was reduced from a few days to minutes after approximately sixty minutes of training. PMID- 26851619 TI - Leptin concentrations in finishing beef steers and heifers and their association with dry matter intake, average daily gain, feed efficiency, and body composition. AB - The objective of this experiment was to determine the association of circulating plasma leptin concentrations with production and body composition measures of finishing beef steers and heifers and to determine if multiple sampling time points improve the associations of plasma leptin concentrations with production and body composition traits. Individual dry matter intake (DMI) and ADG were determined for 84 d using steers and heifers (n = 127 steers and n = 109 heifers). Blood was collected on day 0, day 42, and day 83 for determination of plasma leptin concentrations. Leptin concentrations were greater in heifers than those in steers on day 0 (P < 0.001 for sex by day interaction), and leptin concentrations increased in both sexes but were not different from each other on day 83. Leptin concentrations at all 3 time points and the mean were shown to be positively associated with DMI (P <= 0.006), whereas the mean leptin concentration explaining 8.3% of the variance of DMI. Concentrations of leptin at day 42, day 83, and the mean of all 3 time points were positively associated with ADG (P <= 0.011). Mean leptin concentration was negatively associated with gain:feed ratio and positively associated with residual feed intake (RFI), indicating that more efficient cattle had lower leptin concentrations. However, leptin concentrations explained very little of the variation in residual feed intake (<= 3.2% of the variance). Leptin concentrations were positively associated with body fat measured by ultrasonography at the 12th rib and over the rump (P < 0.001), with the mean leptin concentration explaining 21.9% and 12.7% of the variance in 12th rib and rump fat thickness, respectively. The same trend was observed with carcass composition where leptin concentrations were positively associated with 12th rib fat thickness, USDA-calculated yield grade (YG), and marbling score (P <= 0.006) and mean leptin concentration explained 16.8, 18.2, and 4.6% of the variance for 12th rib fat thickness, yield grade, and marbling score, respectively. Given these and previous results, it appears that leptin physiology could be a candidate for mechanisms that contribute to feed intake and feed efficiency variation in beef cattle. PMID- 26851620 TI - Sublingual microvascular perfusion is altered during normobaric and hyperbaric hyperoxia. AB - Hyperoxia and hyperbaric oxygen therapy can restore oxygen tensions in tissues distressed by ischemic injury and poor vascularization and is believed to also yield angiogenesis and regulate tissue perfusion. The aim of this study was to develop a model in which hyperoxia-driven microvascular changes could be quantified and to test the hypothesis that microcirculatory responses to both normobaric (NB) and hyperbaric (HB) hyperoxic maneuvers are reversible. Sublingual mucosa microcirculation vessel density, proportion of perfused vessels, vessel diameters, microvascular flow index, macrohemodynamic, and blood gas parameters were examined in male rabbits breathing sequential O2/air mixtures of 21%, 55%, 100%, and return to 21% during NB (1.0 bar) and HB (2.5 bar) conditions. The results indicate that NB hyperoxia (55% and 100%) produced significant decreases in microvascular density and vascular diameters (p<0.01 and p<0.05, respectively) accompanied by significant increases in systolic and mean arterial blood pressure (p<0.05, respectively) with no changes in blood flow indices when compared to NB normoxia. HB normoxia/hyperoxia resulted in significant decreases in microvascular density (p<0.05), a transient rise in systolic blood pressure at 55% (p<0.01), and no changes in blood vessel diameter and blood flow indices when compared to NB hyperoxia. All microcirculation parameters reverted back to normal values upon return to NB normoxia. We conclude that NB/HB hyperoxia-driven changes elicit reversible physiological control of sublingual mucosa blood perfusion in the presence of steady cardiovascular function and that the absence of microvascular vasoconstriction during HB conditions suggests a beneficial mechanism associated with maintaining peak tissue perfusion states. PMID- 26851621 TI - Endoscopic ampullectomy of simultaneous major and minor papilla adenomas in a patient with attenuated familial adenomatous polyposis. PMID- 26851622 TI - Cowden syndrome with multiple venous malformations in the small bowel. PMID- 26851623 TI - Small-bowel obstruction due to a migrated lumen-apposing metal stent. PMID- 26851625 TI - Nectins and nectin-like molecules (Necls): Recent findings and their role and regulation in spermatogenesis. AB - Nectins and nectin-like molecules (Necls) belong to Ca2+-independent immunoglobulin superfamily of cell adhesion molecules and they are ubiquitously expressed in most tissues. They not only interact in trans-homo and trans-hetero with others, but also interact in cis with growth factor receptors and integrins. Owning to these properties, nectins and Necls exert their role far beyond cell cell adhesion. Nectins and Necls are crucial for various cellular processes not limited to cell movement, cell proliferation and polarization. They are involved in organogenesis and developmental processes such as spermatogenesis. This review aims to provide an overview and highlight some recent findings on nectins and Necls in the field with emphasis on studies in the testis, upon which future studies can be designed to delineate the role and regulation of nectins and Necls in spermatogenesis. PMID- 26851624 TI - Using Xenopus to study genetic kidney diseases. AB - Modern sequencing technology is revolutionizing our knowledge of inherited kidney disease. However, the molecular role of genes affected by the rapidly rising number of identified mutations is lagging behind. Xenopus is a highly useful, but underutilized model organism with unique properties excellently suited to decipher the molecular mechanisms of kidney development and disease. The embryonic kidney (pronephros) can be manipulated on only one side of the animal and its formation observed directly through the translucent skin. The moderate evolutionary distance between Xenopus and humans is a huge advantage for studying basic principles of kidney development, but still allows us to analyze the function of disease related genes. Optogenetic manipulations and genome editing by CRISPR/Cas are exciting additions to the toolbox for disease modelling and will facilitate the use of Xenopus in translational research. Therefore, the future of Xenopus in kidney research is bright. PMID- 26851626 TI - Evaluating network inference methods in terms of their ability to preserve the topology and complexity of genetic networks. AB - Network inference is a rapidly advancing field, with new methods being proposed on a regular basis. Understanding the advantages and limitations of different network inference methods is key to their effective application in different circumstances. The common structural properties shared by diverse networks naturally pose a challenge when it comes to devising accurate inference methods, but surprisingly, there is a paucity of comparison and evaluation methods. Historically, every new methodology has only been tested against gold standard (true values) purpose-designed synthetic and real-world (validated) biological networks. In this paper we aim to assess the impact of taking into consideration aspects of topological and information content in the evaluation of the final accuracy of an inference procedure. Specifically, we will compare the best inference methods, in both graph-theoretic and information-theoretic terms, for preserving topological properties and the original information content of synthetic and biological networks. New methods for performance comparison are introduced by borrowing ideas from gene set enrichment analysis and by applying concepts from algorithmic complexity. Experimental results show that no individual algorithm outperforms all others in all cases, and that the challenging and non-trivial nature of network inference is evident in the struggle of some of the algorithms to turn in a performance that is superior to random guesswork. Therefore special care should be taken to suit the method to the purpose at hand. Finally, we show that evaluations from data generated using different underlying topologies have different signatures that can be used to better choose a network reconstruction method. PMID- 26851627 TI - Stem cell mitochondria during aging. AB - Mitochondria are the central hubs of cellular metabolism, equipped with their own mitochondrial DNA (mtDNA) blueprints to direct part of the programming of mitochondrial oxidative metabolism and thus reactive oxygen species (ROS) levels. In stem cells, many stem cell factors governing the intricate balance between self-renewal and differentiation have been found to directly regulate mitochondrial processes to control stem cell behaviors during tissue regeneration and aging. Moreover, numerous nutrient-sensitive signaling pathways controlling organismal longevity in an evolutionarily conserved fashion also influence stem cell-mediated tissue homeostasis during aging via regulation of stem cell mitochondria. At the genomic level, it has been demonstrated that heritable mtDNA mutations and variants affect mammalian stem cell homeostasis and influence the risk for human degenerative diseases during aging. Because such a multitude of stem cell factors and signaling pathways ultimately converge on the mitochondria as the primary mechanism to modulate cellular and organismal longevity, it would be most efficacious to develop technologies to therapeutically target and direct mitochondrial repair in stem cells, as a unified strategy to combat aging-related degenerative diseases in the future. PMID- 26851629 TI - Gene silencing of MCP-1 prevents microglial activation and inflammatory injury after intracerebral hemorrhage. AB - Microglia are activated after intracerebral hemorrhage and induce neuron death by releasing proinflammatory cytokines and chemokines. However, the related mechanism of microglia activation in such conditions remains elusive. MCP-1, the ligand of CCR2 expressed in the central nervous system, could promote microglia proliferation, survival and cytokine secretion. According to the previous findings, we make a hypothesis that whether alternation of MCP-1 level could attenuate microglia activation and toxicity to neuron in intracerebral hemorrhage. To identify that, we interfere with the MCP-1 expression of microglia by RNAi technology, and coculture the microglia and neuron in ICH. The results demonstrated that MCP-1 RNAi inhibited TNF-alpha, IL-1beta and IL-6 expression in microglia and attenuated neuron injury. In conclusion, the present study suggests that MCP-1 might promote ICH induced microglia activation and toxicity to neuron, and MCP-1 RNAi might provide promising therapeutical strategy for ICH. PMID- 26851630 TI - Madecassoside suppresses proliferation and invasiveness of HGF-induced human hepatocellular carcinoma cells via PKC-cMET-ERK1/2-COX-2-PGE2 pathway. AB - Recent studies showed that Madecassoside (MAD), a pentacyclic triterpene isolated from Centella asitica (L.), was used as a therapeutic agent in wound healing and also as an anti-inflammatory, anti-oxidative activities and anti-aging agent. However, its role in cancer has not been elucidated. In our present study, hepatocyte growth factor (HGF) induced the phosphorylation of its corresponding receptor cMET, increased expression of cyclo-oxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in human hepatocellular carcinoma (HCC) cells lines (HepG2 and SMMC-77), and this effect was inhibited by MAD in a dose-dependent manner. In addition, MAD exhibited significant anti-proliferative and anti invasive effect in HGF-induced HepG2 and SMMC-77 cells. Moreover, MAD inhibited the phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and the protein kinase C (PKC) activity in HGF-induced HepG2 and SMMC-77 cells. This conclusion was consistent with the effect of selective COX-2 inhibitor (NS-398) and knockdown of COX-2 by siRNA on attenuating the proliferation and invasiveness potential, and over-expression of COX-2 on abolishing the effects of MAD on proliferation and invasiveness potential, and was also in parallel with the effect of PKC inhibitor (Bisindolylmaleimide) on inhibiting PKC activity, MEK/ERK1/2 inhibitor (PD98059) inhibited MEK/ERK1/2 pathways in HGF-induced HepG2 and SMMC-77 cells. Collectively, MAD could inhibit the HGF-activated proliferation and invasiveness of HCC cells via regulating the activation of cMET PKC-ERK1/2-COX-2-PGE2 cascade, which indicated that MAD might help control HGF linked HCC. PMID- 26851628 TI - Frogs as integrative models for understanding digestive organ development and evolution. AB - The digestive system comprises numerous cells, tissues and organs that are essential for the proper assimilation of nutrients and energy. Many aspects of digestive organ function are highly conserved among vertebrates, yet the final anatomical configuration of the gut varies widely between species, especially those with different diets. Improved understanding of the complex molecular and cellular events that orchestrate digestive organ development is pertinent to many areas of biology and medicine, including the regeneration or replacement of diseased organs, the etiology of digestive organ birth defects, and the evolution of specialized features of digestive anatomy. In this review, we highlight specific examples of how investigations using Xenopus laevis frog embryos have revealed insight into the molecular and cellular dynamics of digestive organ patterning and morphogenesis that would have been difficult to obtain in other animal models. Additionally, we discuss recent studies of gut development in non model frog species with unique feeding strategies, such as Lepidobatrachus laevis and Eleutherodactylous coqui, which are beginning to provide glimpses of the evolutionary mechanisms that may generate morphological variation in the digestive tract. The unparalleled experimental versatility of frog embryos make them excellent, integrative models for studying digestive organ development across multiple disciplines. PMID- 26851631 TI - Zhen-wu-tang attenuates cationic bovine serum albumin-induced inflammatory response in membranous glomerulonephritis rat through inhibiting AGEs/RAGE/NF kappaB pathway activation. AB - Zhen-wu-tang (ZWT), a traditional Chinese compound formula recorded in the Treatise on Febrile Diseases, has significant inhibitory effects on inflammatory damage and oxidative lesions in rats, but its mechanism of action remains unclear. The aim of the present study was to explore whether the anti inflammatory and anti-oxidative effects of ZWT were mediated by the AGEs/RAGE/NF kappaB signaling pathway in rats with cationic bovine serum albumin (C-BSA) induced membranous glomerulonephritis (MGN). We found that ZWT significantly reduced the production of malondialdehyde (MDA), but enhanced the superoxide dismutase (SOD) activity. The ELISA results showed that ZWT not only reduced the serum levels of AGEs but also decreased the release of inflammatory mediators (TNF-alpha, IL-1beta, and IL-6). Meanwhile, HE staining showed that pathological kidney injury was alleviated by ZWT. In addition, ZWT suppressed the expression of RAGE1 and NF-kappaB p65, as well as the nuclear translocation of NF-kappaB p65. The accumulation of AGEs, oxidative lesions and inflammation damage were reduced by an AGE inhibitor. Thus, the present study demonstrates that AGEs play a role in the pathogenesis of MGN and that AGE inhibition could reduce the inflammatory reactions and oxidative lesions in MGN. In general, ZWT attenuated MGN, in part, by inhibiting the AGEs/RAGE/NF-kappaB pathway. PMID- 26851633 TI - The use of incinerated pig head in dental identification simulation. AB - PURPOSE: The aim of this exercise was to simulate a disaster victim identification scenario to allow training in documentation of postmortem incinerated remains and reconciliation of dental data. METHOD: Varying number of restorations were placed in ten pig heads. The teeth and restorations were charted, with the restorations radiographed and documented, creating an ante mortem data set. The following day the heads were cremated. Following cooling and recording they were transported for a post-mortem examination by trained specialist odontologists who were not involved in the initial antemortem phase. Recordings included the charting of teeth, restorations, lost teeth, and radiographs to simulate a post-mortem examination. A reconciliation of postmortem to antemortem information was attempted. RESULTS: There was an unacceptable amount of error in the postmortem examination of the heads. The errors related mainly to avulsed teeth and incorrect opinion of which charted surfaces the restorations were placed upon. Also noted were a considerable number of root fractures occurring beneath the crestal bone. This observation does not mimic the evidence observed in human incinerated teeth where the crowns tend to fracture off the roots at the dentin-enamel junction. CONCLUSION: The use of incinerated pig (Sus Scrofa) heads is not an ideal model for forensic odontology training in disaster victim identification. Differences in both anatomy and behavior following exposure to heat were shown to hamper documentation and subsequent comparison to antemortem data. PMID- 26851634 TI - Dental Patterns in Peruvians: A Panoramic Radiography Study. AB - The dental pattern is defined as the combination of distinct codes assigned to describe specific tooth conditions including virgin, missing, and restored teeth that comprise the complete dentition or from discrete groups of teeth. This pattern can be then compared to the dentition of individual/s in an attempt to determine positive identification. The aims of the present investigation were to study and determine the diversity of dental patterns in Peruvian citizens based on a sample of panoramic radiographs. Digital panoramic radiographs of 900 adult Peruvian patients (450 female and 450 male) were evaluated to determine the dental patterns. The most frequent dental patterns found in the complete dentition, maxillae, upper-anterior and lower-anterior sextants were all-virgin teeth (0.3%), all-extracted teeth (1.9%), all-virgin teeth (1%) and all-virgin teeth (34.2% and 72.3%) respectively. The diversity was calculated by the use of the Simpson's diversity index, the resulting values for the full-dentition, maxilla and mandible were over the 99.8% value and were similar to those previously reported in the scientific literature. This study demonstrates the positive benefit of dental patterns in the process of identification. Additionally a combination of codes is proposed that could prove useful in cases where a better radiographic description is required. PMID- 26851635 TI - Prediction of anthropometric measurements from tooth length--A Dravidian study. AB - BACKGROUND: Anthropometric measurement is essential for identification of both victims and suspects. Often, this data is not readily available in a crime scene situation. The availability of one data set should help in predicting the other. This study was hypothesised on the basis of a correlation and geometry between the tooth length and various body measurements. AIM AND OBJECTIVE: To correlate face, palm, foot and stature measurements with tooth length. To derive a regression formula to estimate the various measurements from tooth length. MATERIALS AND METHODS: The present study was conducted on Dravidian dental students in the age group 18 - 25 with a sample size of 372. All of the dental and physical parameters were measured using standard anthropometric equipments and techniques. RESULTS: The data was analysed using SPSS software and the methods used for statistical analysis were linear regression analysis and Pearson correlation. The parameters (incisor height (IH), face height (FH), palm length (PL), foot length (FL) and stature (S) showed nil to mild correlation (R = 0.2 <= 0.4) except for palm length (PL) and foot length (FL). (R>0.6). CONCLUSION: It is concluded that odontometric data is not a reliable source for estimating the face height (FH), palm length (PL), foot length (FL) and stature (S). PMID- 26851632 TI - Therapeutic advances for the tumors associated with neurofibromatosis type 1, type 2, and schwannomatosis. AB - Neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN) are tumor-suppressor syndromes. Each syndrome is an orphan disease; however, the tumors that arise within them represent the most common tumors of the nervous system worldwide. Systematic investigation of the pathways impacted by the loss of function of neurofibromin (encoded byNF1) and merlin (encoded byNF2) have led to therapeutic advances for patients with NF1 and NF2. In the syndrome of SWN, the genetic landscape is more complex, with 2 known causative genes (SMARCB1andLZTR1) accounting for up to 50% of familial SWN patients. The understanding of the molecular underpinnings of these syndromes is developing rapidly and offers more therapeutic options for the patients. In addition, common sporadic cancers harbor somatic alterations inNF1(ie, glioblastoma, breast cancer, melanoma),NF2(ie, meningioma, mesothelioma) andSMARCB1(ie, atypical teratoid/rhabdoid tumors) such that advances in management of syndromic tumors may benefit patients both with and without germline mutations. In this review, we discuss the clinical and genetic features of NF1, NF2 and SWN, the therapeutic advances for the tumors that arise within these syndromes and the interaction between these rare tumor syndromes and the common tumors that share these mutations. PMID- 26851636 TI - Can mandibular lingual canals be used as a forensic fingerprint? AB - OBJECTIVES: This study aimed to identify whether the lingual canals of the mandible can be used as a unique fingerprint when dealing with forensic victim identification. MATERIALS AND METHODS: The study consisted of two parts; an observational part and an objective image analysis part. In the observational part a total of 100 in vivo high resolution CBCT datasets of human mandibles were included in the process of simulated matching of ante-mortem (AM) and post-mortem (PM) data. For the objective image analysis part 10 dry human mandibles were scanned with 2 different Cone Beam Computed tomography (CBCT) machines. In the observational part of the study trained observers attempted to correctly identify matching pairs of images taken from the same mandible out of a series of 100 mandibles. The aim was to simulate matching of the neurovascular structures on AM and PM mandibular midline images and determine the percentage of mandibles identified correctly. In the objective image analysis part, simulated matching was carried out using a specific CBCT dataset acquired to mimic a PM dataset and 10 datasets acquired from a different CBCT device which served as the source of potential AM cases. Comparison between AM and PM datasets resulted in the matching of the AM data and PM data obtained from the same mandible, leading to an assumed correct identification. RESULTS: The observational part of the study showed an average 95% correct identification of the mandibular midline neurovascular structures. Registration of mandibles resulted in perfect overlap of the same mandible from 2 different CBCT machine with an error distance equalling zero, while the registration of different mandibles deviated on average error distance 0.13 mm to 0.18 mm. CONCLUSION: The percentage of fit for the simulated AM and PM data of the same mandible was 100%. This finding together with the significant deviations noted for the non-matching cases, may have a potential role in forensic identification in the same way that fingerprints are recognised as being a unique identifying feature. PMID- 26851637 TI - Combinatorial immunotherapy strategies for hepatocellular carcinoma. AB - Hepatocellular carcinoma (HCC) is the most common liver malignancy. The prognosis for HCC patients greatly varies according to the stage at diagnosis. Overall it is poor, with a 5-year survival rate of approximately 5-6%. Immunotherapeutic interventions represent a novel and effective therapeutic tool. However, only few immunotherapy trials for HCC have been conducted so far with contrasting results, suggesting that significant improvements are needed. Indeed, the liver is characterized by a strong intrinsic immune suppressive microenvironment which needs to be counterbalanced with immune stimulatory approaches. Therefore, the implementation of combinatorial protocols combining immune stimulatory strategies with specific immunotherapy approaches could result in a dramatic improvement of efficacy and clinical outcome in HCC patients. The present review aims at describing the state of the art in immunotherapy strategies for HCC and future perspectives. PMID- 26851638 TI - Beyond magnitude: Judging ordinality of symbolic number is unrelated to magnitude comparison and independently relates to individual differences in arithmetic. AB - In the field of numerical cognition, ordinality, or the sequence of numerals, has received much less attention than cardinality, or the number of items in a set. Therefore it is unclear whether the numerical effects generated from ordinality and cardinality tasks are associated, and whether they relate to math achievement and more domain-general variables in similar ways. To address these questions, sixty adults completed ordinality, cardinality, visual-spatial working memory, inhibitory control and math achievement tasks. The numerical distance effect from the cardinality task and the reverse distance effect from the ordinality task were both relatively reliable but not statistically significantly associated with one another. Additionally, both distance effects predicted independent unique variance in math scores, even when visual-spatial working memory and inhibitory control were included in the regression model. These findings provide support for dissociation in the mechanisms underlying cardinal and ordinal processing of number symbols and thereby highlight the critical role played by ordinality in symbolic numerical cognition. PMID- 26851639 TI - Functional analysis of Torpedo californica nicotinic acetylcholine receptors in multiple activation states by SSM-based electrophysiology. AB - Organophosphorus compounds (OPC), i.e. nerve agents or pesticides, are highly toxic due to their strong inhibition potency against acetylcholinesterase (AChE). Inhibited AChE results in accumulation of acetylcholine in the synaptic cleft and thus the desensitisation of the nicotinic acetylcholine receptor (nAChR) in the postsynaptic membrane is provoked. Direct targeting of nAChR to reduce receptor desensitisation might be an alternative therapeutic approach. For drug discovery, functional properties of potent therapeutic candidates need to be investigated in addition to affinity properties. Solid supported membrane (SSM)-based electrophysiology is useful for functional characterisation of ligand-gated ion channels like nAChRs, as charge translocations via capacitive coupling of the supporting membrane can be measured. By varying the agonist (carbamoylcholine) concentration, different functional states of the nAChR were initiated. Using plasma membrane preparations obtained from Torpedo californica electric organ, functional properties of selected nAChR ligands and non-oxime bispyridinium compounds were investigated. Depending on overall-size, the bispyridinium compounds enhanced or inhibited cholinergic signals induced by 100 MUM carbamoylcholine. Applying excessive concentrations of the agonist carbamoylcholine provoked desensitisation of the nAChRs, whereas addition of bispyridinium compounds bearing short alkyl linkers exhibited functional recovery of previously desensitised nAChRs. The results suggest that these non-oxime bispyridinium compounds possibly interacted with nAChR subtypes in a manner of a positive allosteric modulator (PAM). The described newly developed functional assay is a valuable tool for the assessment of functional properties of potential compounds such as nAChR modulating ligands, which might be a promising approach in the therapeutically treatment of OPC-poisonings. PMID- 26851640 TI - An evaluation of concentrations of styrene-7,8-oxide in rats and humans resulting from exposure to styrene or styrene-7,8-oxide and potential genotoxicity. AB - There is potential for oral exposure of humans to styrene (ST) such as from migration of residual levels in polystyrene food containers. After absorption, ST is metabolised to styrene-7,8-oxide (SO), an alkylating epoxide. Hence, a comparison of blood burdens of SO resulting from oral exposures to ST was made with SO burdens possibly warranting genotoxic concern. A validated physiological toxicokinetic model was used for the assessment. Model calculations predicted for exposures to ST that maximum concentrations of SO in venous blood of rats and humans should not exceed 0.33 MUg/ml and 0.036 MUg/ml, respectively, because of saturation of the SO formation from ST. The daily area under the concentration time curve of SO in venous blood (AUCSO) was directly proportional to the dose of ST (mg/kg body weight; BW), independent of the exposure route (inhalation or oral exposure). In resting humans, the daily AUCSO was about half that in rats at the same amount of ST/kg BW (calculated up to 100mg ST/kg BW in humans). Taking into account the results of cytogenetic studies in ST-exposed rats, it was deduced that no genotoxic effects of SO are to be expected in ST-exposed humans, at least up to a daily amount of 100mg ST/kg BW, which is equivalent to 100 times the amount originating from the Overall Migration Limit in the EU for ST migrating from food contact plastics. Therefore, no potential genotoxic concern is predicted for ST uptake from food packaging, based on the reported combined measured and modelled data. PMID- 26851641 TI - Kinetic analysis of interactions of amodiaquine with human cholinesterases and organophosphorus compounds. AB - Standard therapy of poisoning by organophosphorus compounds (OP) is a combined administration of an anti-muscarinic drug (e.g. atropine) and an oxime as reactivator of inhibited acetylcholinesterase (AChE). Limited efficacy of clinically used oximes against a variety of OPs was shown in numerous studies, calling for research on novel reactivators of OP-inhibited AChE. Recently, reactivation of OP-inhibited AChE by the antimalarial drug amodiaquine was reported. In the present study, amodiaquine and its interactions with human cholinesterases in presence or absence of OP nerve agents was investigated in vitro. Thereby, reversible inhibition of human cholinesterases by amodiaquine (AChE ? BChE) was observed. Additionally, a mixed competitive-non-competitive inhibition type of amodiaquine with human AChE was determined. Slow and partial reactivation of sarin-, cyclosarin- and VX-inhibited cholinesterases by amodiaquine was recorded, amodiaquine failed to reactivate tabun-inhibited human cholinesterases. Amodiaquine, being a potent, reversible AChE inhibitor, was tested for its potential benefit as a pretreatment to prevent complete irreversible AChE inhibition by the nerve agent soman. Hereby, amodiaquine failed to prevent phosphonylation and resulted only in a slight increase of AChE activity after removal of amodiaquine and soman. At present the molecular mechanism of amodiaquine-induced reactivation of OP-inhibited AChE is not known, nevertheless amodiaquine could be considered as a template for the design of more potent non-oxime reactivators. PMID- 26851642 TI - The role of the Wnt/beta-catenin-Annexin A1 pathway in the process of sevoflurane induced cognitive dysfunction. AB - Postoperative cognitive decline (POCD) is a common geriatric complication, and sevoflurane is a widely accepted inducer of POCD. Although the aetiology of POCD is not clear, a breach in the blood-brain barrier (BBB) is involved in early POCD. Annexin A1 has shown protective effects on BBB function. The objective of this study was to investigate both the effects of sevoflurane on the components of the BBB and the underlying mechanism. In vivo treatment with 3.6% sevoflurane for 6 h disrupted BBB components led to fibrinogen invasion and down-regulation of Annexin A1 expression at 24 h after inhalation. The administration of human recombinant Annexin A1 (hr Annexin A1) attenuated the disruption of BBB components, thereby reducing fibrinogen invasion. In addition, the administration of hr Annexin A1 improved cognitive function after the inhalation of 3.6% sevoflurane for 6 h. Moreover, in cultured endothelial cells, 3.6% sevoflurane for 6 h increased GSK-3beta and decreased beta-catenin levels at 24 h after inhalation. The activation/inhibition of the Wnt/beta-catenin signalling pathway attenuated/worsened the sevoflurane-induced decrease in Annexin A1. Our findings indicate that in endothelial cells, treatment with 3.6% sevoflurane for 6 h inhibits the Wnt/beta-catenin signalling pathway, thereby increasing GSK-3beta and decreasing beta-catenin. By inhibiting this pathway, the gas anaesthetic sevoflurane down-regulated Annexin A1, which consequently breached the BBB and induced POCD. We propose the following cascade for sevoflurane-induced cognitive dysfunction: in microvascular endothelial cells, treatment with 3.6% sevoflurane for 6 h inhibits the Wnt/beta-catenin signalling pathway, increasing GSK-3beta and decreasing beta-catenin, which down-regulates the expression of Annexin A1. This cascade leads to a breach in the blood-brain barrier, a process which is involved in the occurrence of early postoperative cognitive decline. Cover Image for this issue: doi: 10.1111/jnc.13314. PMID- 26851643 TI - Family factors contributing to emotional and behavioral problems in Korean adolescents with epilepsy. AB - PURPOSE: We aimed to determine whether different aspects of family functioning are associated with emotional and behavioral problems in adolescents with epilepsy and, if not, to document any indirect associations mediated by other family factors. METHODS: This was a cross-sectional, multicenter study. A total of 297 adolescents with epilepsy and their parents participated. Adolescent psychopathology was measured using the Youth Self-Report. Family factors were classified into proximal (parent-child interaction), distal (parent characteristics), and contextual factors (family characteristics) in accordance to their level of proximity to the adolescent's everyday life. Regression analyses were used to analyze the unique and combined predictive power of family factors in relation to psychopathology. RESULTS: In total, 44 (14.8%) and 51 (17.2%) adolescents with epilepsy scored above the borderline cutoff (T-score >= 60) of internalizing and externalizing problems, respectively. Proximal and distal factors were independently associated with both internalizing and externalizing problems. High levels of parental depressive mood and parental overcontrol were the strongest factors contributing to internalizing and externalizing problems, respectively. Contextual factors were indirectly associated with both internalizing and externalizing problems through more proximal factors. CONCLUSIONS: Both proximal and distal family factors affect psychopathology in Korean adolescents with epilepsy. Parental feelings of depression and parental overcontrol are the strongest factors contributing to internalizing and externalizing problems, respectively. PMID- 26851644 TI - Parent health literacy and adherence-related outcomes in children with epilepsy. AB - BACKGROUND: The relationship between parent health literacy and adherence to treatment in children with epilepsy has not been fully explored. The purpose of this study was to determine whether parent health literacy and other variables predicted factors associated with adherence, such as missed medication doses, missed medical appointments, and seizure frequency, in children with epilepsy between 1 and 12 years old. METHODS: It was hypothesized that parents with adequate parent health literacy would report fewer missed doses, missed appointments, and seizure occurrences. Using a nonexperimental, cross-sectional study design, interviews were conducted with 146 parents and guardians of children with epilepsy who resided in rural communities. Univariate analyses, including ANOVA, and multiple linear regressions were conducted. RESULTS: Results indicated that parent health literacy was the strongest predictor of two of the adherence-related factors. Higher health literacy scores were associated with fewer missed medication doses and seizure occurrences. However, health literacy was not associated with missed medical appointments. Among other study variables, higher household income was also predictive of fewer missed doses. CONCLUSION: The study findings suggest that inadequate health literacy among parents may serve as an independent risk factor for adherence-related outcomes among children with epilepsy. Further research, as well as effective, targeted parent health literacy strategies used to improve epilepsy management and care in children, is recommended. PMID- 26851645 TI - EEG epileptiform abnormalities at admission to a rehabilitation department predict the risk of seizures in disorders of consciousness following a coma. AB - BACKGROUND: Seizures affect about a quarter of patients with disorders of consciousness (DOC) after a coma. AIMS: We investigated whether the presence of epileptiform abnormalities (EAs) in the electroencephalogram (EEG) of patients with DOC may predict the occurrence of seizures. Moreover, we evaluated whether EAs have a prognostic role in these patients. METHODS: This was a retrospective single-center cohort study of patients hospitalized between January 2005 and December 2014 in a rehabilitation department (mean time from acute brain injury: 46.1 days). We analyzed 30-minute EEGs at admittance for 112 patients with unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS), then compared occurrence of seizures over the following three months across patients with absent, unilateral, and bilateral EAs (generalized or bilateral independent). Outcomes at three months were assessed in the same groups using the Coma Recovery Scale Revised. RESULTS: Epileptiform abnormalities were observed in 38 patients (33.9%). Of these, 25 were unilateral, and 13 were bilateral. Seizures occurred in 84.6% of patients with bilateral EAs, which was significantly higher than in patients without EAs (10.8%, p<0.001) or with unilateral EAs (24%, p=0.001). The presence of EAs was not related to etiology or different DOC and did not significantly affect outcomes at three months. CONCLUSIONS: Patients with EAs at admission to a rehabilitation department have an increased risk of seizures. Specifically, most patients with bilateral EAs had seizures within the following 3 months. Evaluation of EAs in EEGs of patients with DOC may give valuable information in the management of antiepileptic drug treatment. PMID- 26851646 TI - Psychiatric comorbidity in children and youth with epilepsy: An association with executive dysfunction? AB - OBJECTIVES: Psychopathology in children and youth with epilepsy has previously been related to executive dysfunction, but the nature of the association is uncertain. We sought to explore risk factors for psychiatric disorders in children and youth with epilepsy, with emphasis on executive dysfunction, along with seizure-related and psychosocial factors. METHODS: The cohort consisted of one hundred and one consecutive patients aged 10-19 years with focal (n=52) or genetic generalized (n=49) epilepsy. All were screened for psychiatric symptoms, using part of an extensive questionnaire, the Strengths and Difficulties Questionnaire (SDQ) for both patients and their parents. Participants scoring in the borderline or abnormal range on the SDQ received a psychiatric interview (Kiddie-SADS-PL). All participants underwent a neuropsychological examination, and those with general cognitive abilities (IQ)<70 were excluded. RESULTS: Forty seven of 101 participants (46.5%) had a SDQ score in the borderline or abnormal range and underwent a psychiatric evaluation. Of these, 44 (93.6%) met the criteria for a psychiatric diagnosis, the most common being ADHD and anxiety. An executive deficit was identified in 26.8% of the participants with a psychiatric diagnosis, but in only 5.4% of those without such a diagnosis (p=0.003). Multivariate logistic regression analysis showed that executive dysfunction was an independent risk factor for having a psychiatric disorder (OR 8.2, CI 1.8 37.2, p=0.006), along with male gender (OR 2.9, CI 1.2-7.3, p=0.02), and early seizure onset (0.86-that is one year older equals risk of psychiatric disorder reduced by 14%-CI 0.77-0.96, p=0.01). Other epilepsy-related or psychosocial factors were not significantly associated with psychiatric disorders. CONCLUSIONS: Multiple factors are associated with psychiatric problems in children and youth with epilepsy. In this study, executive dysfunction, male gender, and early epilepsy onset were independent risk factors for having a psychiatric disorder. An evaluation of psychiatric and cognitive problems is important to enable a positive long-term outcome in childhood epilepsy. PMID- 26851647 TI - The neuropsychological outcome of pediatric patients with refractory epilepsy treated with VNS--A 24-month follow-up in Taiwan. AB - OBJECTIVES: Multiple studies have reported the benefits of vagus nerve stimulation (VNS) on neuropsychological outcomes. The aim of this study was to investigate how VNS affects cognition and psychosocial adjustment in children with refractory epilepsy (RE), and to determine the efficacy of VNS in a Taiwanese population. METHODS: We conducted a one-group pretest-posttest study on pediatric patients with RE. The study comprised 19 males and 18 females, all aged <18 years. We recorded seizure frequency at 3, 12, and 24 months after VNS device implantation. Intelligence quotients (IQ) were assessed using the Wechsler Intelligence Scale for Children - IV. The Parental Stress Index (PSI) scores were evaluated by a pediatric psychologist. RESULTS: Vagus nerve stimulation device implantation significantly reduced seizure frequency at 3, 12 and 24 months, especially in young children (<12 years). No significant improvement in IQ test performance was observed, though there were significant improvements in the PSI, especially in young children. CONCLUSIONS: Vagus nerve stimulation device implantation does not significantly improve cognition function, but it does significantly reduce seizure frequency and stress in parent-child relationships, especially in young children (<12 years). These findings suggest that VNS should be considered as an alternative therapy for patients proven to have seizures that are medically refractory, especially those younger than 12 years of age. PMID- 26851648 TI - Serum fetuin-A levels are independently correlated with vascular endothelial growth factor and C-reactive protein concentrations in type 2 diabetic patients with diabetic retinopathy. AB - BACKGROUND: The higher expression of vascular endothelial growth factor (VEGF) and C-reactive protein (CRP) is associated with the development of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM). Fetuin-A is shown to have proangiogenic and proinflammatory effects. METHODS: This study included 245 T2DM patients consisting of 95 cases with non-diabetic retinopathy (NDR), 78 cases with non-proliferative diabetic retinopathy (NPDR) and 72 cases with proliferative diabetic retinopathy (PDR), in addition to 65 healthy controls. Serum fetuin-A, VEGF and CRP concentrations and related parameters were measured. RESULTS: Significant positive correlations were found between fetuin-A and VEGF and CRP, and between VEGF and CRP in T2DM patients (all p<0.001). After adjustment for confounders, fetuin-A was correlated independently with VEGF and CRP in NPDR and PDR patients, but not in NDR subjects. In addition, fetuin-A was correlated independently with HOMA-IR (all 4 groups), HbA1c (NDR, NPDR and PDR groups) and duration of diabetes (PDR group). When compared with NDR and control subjects, NPDR and PDR patients had higher HOMA-IR. CONCLUSIONS: Serum fetuin-A concentrations are independently correlated with VEGF and CRP concentrations in T2DM patients with DR, but not in NDR subjects. PMID- 26851649 TI - Blood arsenic: Pan-India prevalence. AB - INTRODUCTION: Arsenic, a well-known toxic element, has become one of the biggest causes for clinical concerns among elemental toxicities. Arsenicosis has been reported from many regions of the country, especially on exposure induced by ground water contamination. The clinical effects of chronic arsenic toxicity are generally varied and its timely diagnosis and management pose a big challenge. METHODOLOGY: Our study reports analysis of blood arsenic levels in a pan-India cohort of 205,530 including 111,737 males and 93,793 females respectively. The cohort included all age groups from infants to old adults. Arsenic levels were analyzed using the analytical platform of ICP-MS touted to be the gold standard for elemental analysis. RESULT: Blood arsenic levels of >=5 MUg/L were considered high in our study. The total frequency of high arsenic cases detected in the study is 1.37%. The frequency in males was 1.47% and in females it was detected to be 1.25%. Also, maximum cases of high arsenic levels were detected to be from the state of Kerala and in cities from Mumbai. CONCLUSION: Very few studies have recorded the frequency of high arsenic levels in Indians as well as its average blood levels in a pan-India cohort. Our study has made a pilot attempt to highlight the same to generate awareness about this elemental menace in the Indian context. PMID- 26851650 TI - Serum human epididymis protein 4 (HE4) may be a better tumor marker in early lung cancer. AB - BACKGROUND: Human epididymis protein 4 (HE4) had been shown to be an ideal biomarker in ovarian cancer. However, there were fewer reports on its application in lung cancer. We explored the diagnostic value of serum HE4 as a biomarker in early lung cancer by comparing it with other biomarkers. METHODS: 162 individuals including 112 cases of lung cancer at early stage and 50 healthy people as controls were enrolled. The serum concentrations of biomarkers were determined with the Roche Elecsys assays. RESULTS: In comparison to the other biomarkers such as carcinoembryonic antigen (CEA), neuron-specific-enolase (NSE), serum cytokeratin 19 fragment (CYFRA 21-1) and progastrinreleasing peptide (proGRP), serum HE4 was one of the biomarkers with the highest sensitivity (43.8%) and specificity (95.0%) for early lung cancer diagnosis. In terms of histological results, serum HE4 was the best biomarker both in adenocarcinoma (AC) and squamous carcinoma (SC), and serum proGRP was the best in small cell lung cancer (SCLC). The combination of proGRP, NSE and HE4 could determine the histological type of lung cancer with a very high accuracy of 93.8%. CONCLUSIONS: These findings suggested that serum HE4 was a better biomarker in early lung cancer than other frequently-used biomarkers. PMID- 26851651 TI - Oral fluid cocaine and benzoylecgonine concentrations following controlled intravenous cocaine administration. AB - Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral Eze((r)) (OE) and StatSure Saliva SamplerTM (SS) devices, an hour prior to and up to 69 h after 25mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE observed Cmax median (range) concentrations were 932 (394-1574)MUg/L for cocaine and 248 (96.9-953)MUg/L for BE. SS observed cocaine and BE Cmax median (range) concentrations trended lower at 732 (83.3-1892)MUg/L and 360 (77.2-836)MUg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5h and for BE 30.5 and 28.0 h, respectively at 1 MUg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs. PMID- 26851653 TI - Enhanced non-inflammasome mediated immune responses by mannosylated zwitterionic based cationic liposomes for HIV DNA vaccines. AB - Human immunodeficiency virus (HIV) DNA vaccine can induce cellular and humoral immunity. A safe and effective HIV DNA vaccine is urgent need to prevent the spread of acquired immune deficiency syndrome (AIDS). The major drawback of DNA vaccines is the low immunogenicity, which is caused by the poor delivery to antigen presenting cells and insufficient antigen expression. Sparked by the capability of endosomal/lysosomal escape of the zwitterionic lipid distearoyl phosphoethanol-amine-polycarboxybetaine (DSPE-PCB), we attempted to develop a zwitterionic-based cationic liposome with enhanced immunogenicity of DNA vaccines. The mannosylated zwitterionic-based cationic liposome (man-ZCL) was constructed as a DNA vaccine adjuvant for HIV vaccination. Man-ZCL could complex with DNA antigens to form a tight structure and protect them from nuclei enzyme degradation. Benefited from the capability of the specific mannose receptor mediated antigen processing cells targeting and enhanced endosomal/lysosomal escape, the man-ZCL lipoplexes were supposed to promote antigen presentation and the immunogenicity of DNA vaccines. In vitro and in vivo results revealed that man-ZCL lipoplexes showed enhanced anti-HIV immune responses and lower toxicity compared with CpG/DNA and Lipo2k/DNA, and triggered a Th1/Th2 mixed immunity. An antigen-depot effect was observed in the administration site, and this resulted in enhanced retention of DNA antigens in draining lymph nodes. Most importantly, the man-ZCL could assist to activate T cells through a non-inflammasome pathway. These findings suggested that the man-ZCL could be potentially applied as a safe and efficient DNA adjuvant for HIV vaccines. PMID- 26851654 TI - Time-based understanding of DLCO and DLNO. AB - Capture of CO and NO by blood requires molecules to travel by diffusion from alveolar gas to haemoglobin molecules inside RBCs and then to react. One can attach to these processes two times, a time for diffusion and a time for reaction. This reaction time is known from chemical kinetics and, therefore, constitutes a unique physical clock. This paper presents a time-based bottom-up theory that yields a simple expression for DLCO and DLNO that produces quantitative predictions which compare successfully with experiments. Specifically, when this new approach is applied to DLCO experiments, it can be used to determine the value of the characteristic diffusion time, and the value of capillary volume (Vc). The new theory also provides a simple explanation for still unexplained correlations such as the observed proportionality between the so-called membrane conductance DM and Vc of Roughton and Forster's interpretation. This new theory indicates that DLCO should be proportional to the haematocrit as found in several experiments. PMID- 26851652 TI - Pituitary Adenylate cyclase-activating polypeptide orchestrates neuronal regulation of the astrocytic glutamate-releasing mechanism system xc (.). AB - Glutamate signaling is achieved by an elaborate network involving neurons and astrocytes. Hence, it is critical to better understand how neurons and astrocytes interact to coordinate the cellular regulation of glutamate signaling. In these studies, we used rat cortical cell cultures to examine whether neurons or releasable neuronal factors were capable of regulating system xc (-) (Sxc), a glutamate-releasing mechanism that is expressed primarily by astrocytes and has been shown to regulate synaptic transmission. We found that astrocytes cultured with neurons or exposed to neuronal-conditioned media displayed significantly higher levels of Sxc activity. Next, we demonstrated that the pituitary adenylate cyclase-activating polypeptide (PACAP) may be a neuronal factor capable of regulating astrocytes. In support, we found that PACAP expression was restricted to neurons, and that PACAP receptors were expressed in astrocytes. Interestingly, blockade of PACAP receptors in cultures comprised of astrocytes and neurons significantly decreased Sxc activity to the level observed in purified astrocytes, whereas application of PACAP to purified astrocytes increased Sxc activity to the level observed in cultures comprised of neurons and astrocytes. Collectively, these data reveal that neurons coordinate the actions of glutamate related mechanisms expressed by astrocytes, such as Sxc, a process that likely involves PACAP. A critical gap in modeling excitatory signaling is how distinct components of the glutamate system expressed by neurons and astrocytes are coordinated. In these studies, we found that system xc (-) (Sxc), a glutamate release mechanism expressed by astrocytes, is regulated by releasable neuronal factors including PACAP. This represents a novel form of neuron-astrocyte communication, and highlights the possibility that pathological changes involving astrocytic Sxc may stem from altered neuronal activity. PMID- 26851655 TI - Clonal complex 398 methicillin-susceptible Staphylococcus aureus bloodstream infections are associated with high mortality. AB - Within the last decade, methicillin-resistant Staphylococcus aureus belonging to clonal complex 398 (CC398) has become a worldwide threat associated with livestock. More recently, methicillin-susceptible S. aureus (MSSA) belonging to CC398 have been increasingly reported as a cause of invasive infections in patients without livestock contact. We investigated risk factors associated with CC398 bloodstream infections (BSIs) compared with non-CC398 BSIs with a case control study in a French university Hospital. From January 2010 to December 2014, nonduplicate Staphylococcus aureus (SA) isolates responsible for BSIs in adult patient were typed to identify those belonging to CC398. Each adult patient with a CC398 SA BSI (cases) was matched with 2 non-CC398 SA BSI controls randomly selected on the basis of the time at risk, the unit of hospitalization and susceptibility to methicillin. We retrospectively extracted the clinical information from electronic medical records and used conditional logistic regression for univariate and multivariate analyses. We identified 67 CC398 isolates among the 770 SA responsible for BSI in adult patients. All CC398 isolates were susceptible to methicillin. The proportion of CC398 among MSSA increased steadily from 4.6% in 2010 to 15.1% in 2013 and then stabilized at 13.8% in 2014. Factors significantly associated with CC398 MSSA BSIs were healthcare-associated infection (odds ratio (OR) 3.02, 95% confidence interval (CI) 1.19-7.63), history of neurologic disease (OR 2.51, 95% CI 1.13-5.65) and 30 day mortality (OR 2.44, 95% CI 1.23-4.85). PMID- 26851656 TI - EUCAST technical note on isavuconazole breakpoints for Aspergillus, itraconazole breakpoints for Candida and updates for the antifungal susceptibility testing method documents. AB - The Subcommittee on Antifungal Susceptibility Testing (AFST) of the ESCMID European Committee for Antimicrobial Susceptibility Testing (EUCAST) has determined breakpoints for isavuconazole and Aspergillus and for itraconazole and Candida spp., released a new document summarizing existing and new minimum inhibitory concentration ranges for quality control strains and revised the method documents for yeast and mould susceptibility testing. This technical note is based on the EUCAST isavuconazole and itraconazole rationale documents, version 1.0 of the routine and extended internal quality control for antifungal susceptibility testing as recommended by EUCAST, and the E.Def 7.3, E.Def 9.2 and E.Def 9.3 method documents (http://www.eucast.org). PMID- 26851657 TI - Candidaemia after heart valve replacement surgery: recurrence as prosthetic valve endocarditis is an expected over one-year complication. PMID- 26851658 TI - Human betaA3/A1-crystallin splicing mutation causes cataracts by activating the unfolded protein response and inducing apoptosis in differentiating lens fiber cells. AB - betagamma-Crystallins, having a uniquely stable two domain four Greek key structure, are crucial for transparency of the eye lens,. Mutations in lens crystallins have been proposed to cause cataract formation by a variety of mechanisms most of which involve destabilization of the protein fold. The underlying molecular mechanism for autosomal dominant zonular cataracts with sutural opacities in an Indian family caused by a c.215+1G>A splice mutation in the betaA3/A1-crystallin gene CRYBA1 was elucidated using three transgenic mice models. This mutation causes a splice defect in which the mutant mRNA escapes nonsense mediated decay by skipping both exons 3 and 4. Skipping these exons results in an in-frame deletion of the mRNA and synthesis of an unstable p.Ile33_Ala119del mutant betaA3/A1-crystallin protein. Transgenic expression of mutant betaA3/A1-crystallin but not the wild type protein results in toxicity and abnormalities in the maturation and orientation of differentiating lens fibers in c.97_357del CRYBA1 transgenic mice, leading to a small spherical lens, cataract, and often lens capsule rupture. On a cellular level, the lenses accumulated p.Ile33_Ala119del betaA3/A1-crystallin with resultant activation of the stress signaling pathway - unfolded protein response (UPR) and inhibition of normal protein synthesis, culminating in apoptosis. This highlights the mechanistic contrast between mild mutations that destabilize crystallins and other proteins, resulting in their being bound by the alpha-crystallins that buffer lens cells against damage by denatured proteins, and severely misfolded proteins that are not bound by alpha-crystallin but accumulate and have a direct toxic effect on lens cells, resulting in early onset cataracts. PMID- 26851660 TI - Laboratory Information Systems. AB - Laboratory information systems (LISs) supply mission-critical capabilities for the vast array of information-processing needs of modern laboratories. LIS architectures include mainframe, client-server, and thin client configurations. The LIS database software manages a laboratory's data. LIS dictionaries are database tables that a laboratory uses to tailor an LIS to the unique needs of that laboratory. Anatomic pathology LIS (APLIS) functions play key roles throughout the pathology workflow, and laboratories rely on LIS management reports to monitor operations. This article describes the structure and functions of APLISs, with emphasis on their roles in laboratory operations and their relevance to pathologists. PMID- 26851659 TI - One-step chromatographic procedure for purification of B-phycoerythrin from Porphyridium cruentum. AB - B-phycoerythrin (B-PE) was separated and purified from microalga Porphyridium cruentum using one-step chromatographic method. Phycobiliproteins in P. cruentum was extracted by osmotic shock and initially purified by ultrafiltration. Further purification was carried out with a SOURCE 15Q exchange column and analytical grade B-PE was obtained with a purity ratio (A545/A280) of 5.1 and a yield of 68.5%. It showed a double absorption peaks at 545 nm and 565 nm and a shoulder peak at 498 nm, and displayed a fluorescence emission maximum at 580 nm. The analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed a bulky band between 18 and 20 kDa which could be assigned to subunits alpha and beta and a low intensity band of 27 kDa assigned to gamma subunit. Our protocol provides attractive alternative to consider for the purification procedure to obtain analytical grade B-PE at commercial level. PMID- 26851661 TI - Bar Coding and Tracking in Pathology. AB - Bar coding and specimen tracking are intricately linked to pathology workflow and efficiency. In the pathology laboratory, bar coding facilitates many laboratory practices, including specimen tracking, automation, and quality management. Data obtained from bar coding can be used to identify, locate, standardize, and audit specimens to achieve maximal laboratory efficiency and patient safety. Variables that need to be considered when implementing and maintaining a bar coding and tracking system include assets to be labeled, bar code symbologies, hardware, software, workflow, and laboratory and information technology infrastructure as well as interoperability with the laboratory information system. This article addresses these issues, primarily focusing on surgical pathology. PMID- 26851662 TI - Enhancing and Customizing Laboratory Information Systems to Improve/Enhance Pathologist Workflow. AB - Optimizing pathologist workflow can be difficult because it is affected by many variables. Surgical pathologists must complete many tasks that culminate in a final pathology report. Several software systems can be used to enhance/improve pathologist workflow. These include voice recognition software, pre-sign-out quality assurance, image utilization, and computerized provider order entry. Recent changes in the diagnostic coding and the more prominent role of centralized electronic health records represent potential areas for increased ways to enhance/improve the workflow for surgical pathologists. Additional unforeseen changes to the pathologist workflow may accompany the introduction of whole-slide imaging technology to the routine diagnostic work. PMID- 26851663 TI - Specialized Laboratory Information Systems. AB - Some laboratories or laboratory sections have unique needs that traditional anatomic and clinical pathology systems may not address. A specialized laboratory information system (LIS), which is designed to perform a limited number of functions, may perform well in areas where a traditional LIS falls short. Opportunities for specialized LISs continue to evolve with the introduction of new testing methodologies. These systems may take many forms, including stand alone architecture, a module integrated with an existing LIS, a separate vendor supplied module, and customized software. This article addresses the concepts underlying specialized LISs, their characteristics, and in what settings they are found. PMID- 26851664 TI - Laboratory Information Systems Management and Operations. AB - The main mission of a laboratory information system (LIS) is to manage workflow and deliver accurate results for clinical management. Successful selection and implementation of an anatomic pathology LIS is not complete unless it is complemented by specialized information technology support and maintenance. LIS is required to remain continuously operational with minimal or no downtime and the LIS team has to ensure that all operations are compliant with the mandated rules and regulations. PMID- 26851665 TI - Molecular Pathology Informatics. AB - Molecular informatics (MI) is an evolving discipline that will support the dynamic landscape of molecular pathology and personalized medicine. MI provides a fertile ground for development of clinical solutions to bridge the gap between clinical informatics and bioinformatics. Rapid adoption of next generation sequencing (NGS) in the clinical arena has triggered major endeavors in MI that are expected to bring a paradigm shift in the practice of pathology. This brief review presents a broad overview of various aspects of MI, particularly in the context of NGS based testing. PMID- 26851666 TI - Pathology Gross Photography: The Beginning of Digital Pathology. AB - The underutilized practice of photographing anatomic pathology specimens from surgical pathology and autopsies is an invaluable benefit to patients, clinicians, pathologists, and students. Photographic documentation of clinical specimens is essential for the effective practice of pathology. When considering what specimens to photograph, all grossly evident pathology, absent yet expected pathologic features, and gross-only specimens should be thoroughly documented. Specimen preparation prior to photography includes proper lighting and background, wiping surfaces of blood, removing material such as tubes or bandages, orienting the specimen in a logical fashion, framing the specimen to fill the screen, positioning of probes, and using the right-sized scale. PMID- 26851667 TI - Advanced Imaging Techniques for the Pathologist. AB - Advanced imaging refers to direct microscopic imaging of tissue, without the need for traditional hematoxylin-eosin (H&E) microscopy, including microscope slides or whole-slide images. A detailed example is presented of optical coherence tomography (OCT), an imaging technique based on reflected light. Experience and example images are discussed in the larger context of the evolving relationship of surgical pathology to clinical patient care providers. Although these techniques are diagnostically promising, it is unlikely that they will directly supplant H&E histopathology. It is likely that OCT and related technologies will provide narrow, targeted diagnosis in a variety of in vivo (patient) and ex vivo (specimen) applications. PMID- 26851668 TI - Overview of Telepathology. AB - Telepathology is the practice of remote pathology using telecommunication links to enable the electronic transmission of digital pathology images. Telepathology can be used for remotely rendering primary diagnoses, second opinion consultations, quality assurance, education, and research purposes. The use of telepathology for clinical patient care has been limited mostly to large academic institutions. Barriers that have limited its widespread use include prohibitive costs, legal and regulatory issues, technologic drawbacks, resistance from pathologists, and above all a lack of universal standards. This article provides an overview of telepathology technology and applications. PMID- 26851669 TI - Selection and Implementation of New Information Systems. AB - The single most important element to consider when evaluating clinical information systems for a practice is workflow. Workflow can be broadly defined as an orchestrated and repeatable pattern of business activity enabled by the systematic organization of resources into processes that transform materials, provide services, or process information. PMID- 26851670 TI - Health Information Systems. AB - This article provides surgical pathologists an overview of health information systems (HISs): what they are, what they do, and how such systems relate to the practice of surgical pathology. Much of this article is dedicated to the electronic medical record. Information, in how it is captured, transmitted, and conveyed, drives the effectiveness of such electronic medical record functionalities. So critical is information from pathology in integrated clinical care that surgical pathologists are becoming gatekeepers of not only tissue but also information. Better understanding of HISs can empower surgical pathologists to become stakeholders who have an impact on the future direction of quality integrated clinical care. PMID- 26851671 TI - Translational Bioinformatics and Clinical Research (Biomedical) Informatics. AB - Translational bioinformatics and clinical research (biomedical) informatics are the primary domains related to informatics activities that support translational research. Translational bioinformatics focuses on computational techniques in genetics, molecular biology, and systems biology. Clinical research (biomedical) informatics involves the use of informatics in discovery and management of new knowledge relating to health and disease. This article details 3 projects that are hybrid applications of translational bioinformatics and clinical research (biomedical) informatics: The Cancer Genome Atlas, the cBioPortal for Cancer Genomics, and the Memorial Sloan Kettering Cancer Center clinical variants and results database, all designed to facilitate insights into cancer biology and clinical/therapeutic correlations. PMID- 26851672 TI - Training in Informatics: Teaching Informatics in Surgical Pathology. AB - This article presents an overview of the curriculum deemed essential for trainees in pathology, with mapping to the Milestones competency statements. The means by which these competencies desired for pathology graduates, and ultimately practitioners, can best be achieved is discussed. The value of case (problem) based learning in this realm, in particular the kind of integrative experience associated with hands-on projects, to both cement knowledge gained in the lecture hall or online and to expand competency is emphasized. PMID- 26851673 TI - Evaluating the influence of light intensity in mcyA gene expression and microcystin production in toxic strains of Planktothrix agardhii and Microcystis aeruginosa. AB - Cyanobacteria are phytoplanktonic organisms widely occurring in freshwaters, being frequently associated with the production of toxins, namely microcystins (MCs). MCs are produced non-ribosomally by a multienzyme complex (mcy genes). It has been reported that environmental factors, such as light intensity, can influence toxin production. The aim of this study was to assess the influence of light intensity in the transcription of the mcyA gene and corresponding production of microcystins in toxic isolates of Planktothrix agardhii, where little is known, and compare them to Microcystis aeruginosa. For that purpose, cultures were exposed to three different light intensities (4, 20 and 30 MUmol photons m(-2) s(-1)) for 18 days at 20 +/- 1 degrees C. The growth was followed daily using absorbance readings. Samples were collected at each growth stage for cell counting, microcystins quantification and RNA extraction. The level of transcripts was quantified by RT-qPCR and the relative expression determined using 16S rDNA, gltA and rpoC1 as reference genes. The most stable reference genes in M. aeruginosa were rpoC1 and gltA, whereas in P. agardhii were 16S rDNA and gltA. There was a correspondence between the growth rate and light intensity in M. aeruginosa and P. agardhii. The growth rates for both species were lower at 4 and higher at 30 MUmol photons m(-2) s(-1). Microcystin concentration per cell was similar between light intensities in M. aeruginosa and over time, while in P. agardhii it was higher in the stationary phase at 4 MUmol photons m(-2) s(-1). There were differences in the expression of mcyA between the two species. In M. aeruginosa, the highest levels of expression occurred at 4 MUmol photons m(-2) s( 1) in the adaptation phase, whereas for P. agardhii it was at 4MUmol photons m( 2) s(-1) in the exponential growth phase. Our results indicate that the light intensities tested had distinct influences on the growth, microcystin production and mcyA expression levels, presenting considerable differences in M. aeruginosa and P. agardhii. PMID- 26851674 TI - Construction of pTM series plasmids for gene expression in Brucella species. AB - Brucellosis, the most common widespread zoonotic disease, is caused by Brucella spp., which are facultative, intracellular, Gram-negative bacteria. With the development of molecular biology techniques, more and more virulence-associated factors have been identified in Brucella spp. A suitable plasmid system is an important tool to study virulence genes in Brucella. In this study, we constructed three constitutive replication plasmids (pTM1-Cm, pTM2-Amp, and pTM3 Km) using the replication origin (rep) region derived from the pBBR1-MCS vector. Also, a DNA fragment containing multiple cloning sites (MCSs) and a terminator sequence derived from the pCold vector were produced for complementation of the deleted genes. Besides pGH-6*His, a plasmid containing the groE promoter of Brucella spp. was constructed to express exogenous proteins in Brucella with high efficiency. Furthermore, we constructed the inducible expression plasmid pZT 6*His, containing the tetracycline-inducible promoter pzt1, which can induce expression by the addition of tetracycline in the Brucella culture medium. The constructed pTM series plasmids will play an important role in the functional investigation of Brucella spp. PMID- 26851675 TI - Soluble recombinant merozoite surface antigen-142kDa of Plasmodium vivax: An improved diagnostic antigen for vivax malaria. AB - Enzyme Linked Immunosorbent Assay (ELISA), as a serological test, can be a beneficial tool for epidemiological studies by screening blood donors and diagnosis of specific antibodies from Plasmodium vivax (P. vivax) infected cases. Since P. vivax cannot easily be acquired in vitro, ELISA assays using total or semi-purified antigens are seldom used. On the basis of this restriction, we examined whether recombinant protein 42 kDa related to C-terminal region of the merozoite surface antigen-1 of P. vivax (MSA-1(42)) could be suitable for serological detection of vivax malaria infection. Purified recombinant protein produced in Escherichia coli (E. coli) (GST-MSA-1(42)) was examined for its ability to bind to IgG antibodies of individuals with patent P. vivax infection. The method was tested with 262 serum samples collected from individuals living in the south and southeastern regions of Iran where malaria is endemic. Samples exposed to Plasmodium falciparum (P. falciparum) infection and patients with other infectious disease (toxoplasmosis, Leishmania infantum infection, echinococcosis and FUO (fever with unknown origin)) except for P. falciparum were residing in non- malaria endemic areas in Iran. Generally, the sensitivity of ELISA evaluated with sera from naturally infected individuals was 86.9%. The specificity value of the ELISA determined with sera from healthy individuals and from individuals with other infectious diseases was 94.05%. The positive predictive value (PPV), negative predictive value (NPV) provided, and the diagnostic efficiency of anti-rPvMSA-1(42) antibody using indirect ELISA were determined 93.58, 87.77 and 91.06% respectively. Our study demonstrated that, because MSA-1(42) kDa contains both the 33 and 19 kDa fragments in its structure, it can serve as the basis for the development of a sensitive serological test which can be used for epidemiological studies, screening blood donors and diagnosis of P. vivax malaria. PMID- 26851676 TI - Novel triterpenoid AECHL-1 induces apoptosis in breast cancer cells by perturbing the mitochondria-endoplasmic reticulum interactions and targeting diverse apoptotic pathways. AB - BACKGROUND: The modus operandi for an anti-cancer drug must allow for an efficient discrimination system between tumorigenic and non-tumorigenic cells. Targeting ER stress and mitochondrial function in cancer cells appears to be a suitable option, as these processes are dysregulated in tumor cells. AECHL-1, a novel triterpenoid, exhibits potent anticancer activity against an array of cancer cell lines however, its mechanism of action remains elusive. METHODS: Molecular targets of AECHL-1 were investigated using breast adenocarcinoma cells MCF-7, MDA-MB-231 and mammary epithelial cell line MCF 10A in vitro and xenograft tumors in SCID mice in vivo. Western blotting, flow cytometry, and immunohistochemical studies were employed to delineate the molecular pathways. RESULTS: AECHL-1 caused a transient elevation of ER stress proteins along with a prolonged phosphorylation of eIF2alpha in breast cancer cells. This was accompanied by a simultaneous release of calcium from ER stores and subsequent mitochondrial accumulation. These effects could be reversed by using ER stress inhibitors. AECHL-1 brings about mitochondria mediated, caspase independent cell death via AIF in MCF-7 cells; MDA-MB-231 succumbed to caspase dependent extrinsic pathway. Xenograft studies closely echoed our in vitro results. AECHL-1 did not alter cellular and molecular parameters in MCF 10A. CONCLUSION: These findings reveal that, AECHL-1 targets the Achilles Heel of cancer cell, namely dysfunctional ER and mitochondria while being non toxic to normal parenchyma and can thus be further explored as a potential chemotherapeutic intervention. GENERAL SIGNIFICANCE: Aggravation of ER stress by AECHL-1 uncovers a novel pathway for selective elimination of cancer cells. PMID- 26851677 TI - Biomolecule-nanoparticle interactions: Elucidation of the thermodynamics by isothermal titration calorimetry. AB - BACKGROUND: Nanomaterials (NMs) are often exposed to a broad range of biomolecules of different abundances. Biomolecule sorption driven by various interfacial forces determines the surface structure and composition of NMs, subsequently governs their functionality and the reactivity of the adsorbed biomolecules. Isothermal titration calorimetry (ITC) is a nondestructive technique that quantifies thermodynamic parameters through in-situ measurement of the heat absorption or release associated with an interaction. SCOPE OF REVIEW: This review highlights the recent applications of ITC in understanding the thermodynamics of interactions between various nanoparticles (NPs) and biomolecules. Different aspects of a typical ITC experiment that are crucial for obtaining accurate and meaningful data, as well as the strengths, weaknesses, and challenges of ITC applications to NP research were discussed. MAJOR CONCLUSIONS: ITC reveals the driving forces behind biomolecule-NP interactions and the effects of the physicochemical properties of both NPs and biomolecules by quantifying the crucial thermodynamics parameters (e.g., binding stoichiometry, DeltaH, DeltaS, and DeltaG). Complimentary techniques would strengthen the interpretation of ITC results for a more holistic understanding of biomolecule-NP interactions. GENERAL SIGNIFICANCE: The thermodynamic information revealed by ITC and its complimentary characterizations is important for understanding biomolecule-NP interactions that are fundamental to the biomedical and environmental applications of NMs and their toxicological effects. PMID- 26851679 TI - Letter to the Editor. PMID- 26851678 TI - SPARC/osteonectin in mineralized tissue. AB - Secreted protein acidic and rich in cysteine (SPARC/osteonectin/BM40) is one of the most abundant non-collagenous protein expressed in mineralized tissues. This review will focus on elucidating functional roles of SPARC in bone formation building upon results from non-mineralized cells and tissues, the phenotype of SPARC-null bones, and recent discoveries of human diseases with either dysregulated expression of SPARC or mutations in the gene encoding SPARC that give rise to bone pathologies. The capacity of SPARC to influence pathways involved in extracellular matrix assembly such as procollagen processing and collagen fibril formation as well as the capacity to influence osteoblast differentiation and osteoclast activity will be addressed. In addition, the potential for SPARC to regulate cross-linking of extracellular matrix proteins by members of the transglutaminase family of enzymes is explored. Elucidating defined biological functions of SPARC in terms of bone formation and turnover are critical. Further insight into specific cellular mechanisms involved in the formation and homeostasis of mineralized tissues will lead to a better understanding of disease progression. PMID- 26851680 TI - Response to the letter submitted by Dos Santos et al. PMID- 26851681 TI - Theophylline, a methylxanthine drug induces osteopenia and alters calciotropic hormones, and prophylactic vitamin D treatment protects against these changes in rats. AB - The drug, theophylline is frequently used as an additive to medications for people suffering from chronic obstructive pulmonary diseases (COPD). We studied the effect of theophylline in bone cells, skeleton and parameters related to systemic calcium homeostasis. Theophylline induced osteoblast apoptosis by increasing reactive oxygen species production that was caused by increased cAMP production. Bone marrow levels of theophylline were higher than its serum levels, indicating skeletal accumulation of this drug. When adult Sprague-Dawley rats were treated with theophylline, bone regeneration at fracture site was diminished compared with control. Theophylline treatment resulted in a time-dependent (at 4- and 8 weeks) bone loss. At 8 weeks, a significant loss of bone mass and deterioration of microarchitecture occurred and the severity was comparable to methylprednisone. Theophylline caused formation of hypomineralized osteoid and increased osteoclast number and surface. Serum bone resorption and formation marker were respectively higher and lower in the theophylline group compared with control. Bone strength was reduced by theophylline treatment. After 8 weeks, serum 25-D3 and liver 25-hydroxylases were decreased in theophylline group than control. Further, theophylline treatment reduced serum 1, 25-(OH)2 vitamin D3 (1,25-D3), and increased parathyroid hormone and fibroblast growth factor-23. Theophylline treated rats had normal serum calcium and phosphate but displayed calciuria and phosphaturia. Co-administration of 25-D3 with theophylline completely abrogated theophylline-induced osteopenia and alterations in calcium homeostasis. In addition, 1,25-D3 protected osteoblasts from theophylline-induced apoptosis and the attendant oxidative stress. We conclude that theophylline has detrimental effects in bone and prophylactic vitamin D supplementation to subjects taking theophylline could be osteoprotective. PMID- 26851682 TI - Contribution of bacteriochlorophyll conformation to the distribution of site energies in the FMO protein. AB - The structural data for the Fenna-Matthews-Olson (FMO) protein indicate that the bacteriochlorophylls (BChls) display a significant degree of conformational heterogeneity of their peripheral substituents and the protein-induced nonplanar skeletal deformations of the tetrapyrrole macrocycle. As electronic properties of chromophores are altered by such differences, a conformational effect may influence the site-energies of specific pigments and thus play a role in mediating the excitation energy transfer dynamics, but this has not yet been established. The difficulty of assessing this question is shown to be partly the result of the inability of the sequential truncation approach usually employed to account for interactions between the conformations of the macrocycle and its substituents and an alternative approach is suggested. By assigning the BChl atoms to meaningful atom groups and performing all possible permutations of partial optimizations in a full-factorial design, where each group is either frozen in the crystal geometry or optimized in vacuo, followed by excited state calculations on each resulting structure (PM6//ZIndo/S), the specific effects of the conformations of each BChl component as well as mutual interactions between the molecular fragments on the site-energy can be delineated. This factorial relaxation procedure gives different estimates of the macrocycle conformational perturbation than the approach of sequentially truncating the BChl periphery. The results were evaluated in the context of published site-energies for the FMO pigments from three species to identify how conformational effects contribute to their distribution and instances of cross-species conservation and functional divergence of the BChl nonplanarity conformational contribution are described. PMID- 26851683 TI - Diffusion tensor tractography imaging in pediatric epilepsy - A systematic review. AB - PURPOSE: Recent years brought several experimental and clinical reports applying diffusion tensor tractography imaging (DTI) of the brain in epilepsy. This study was aimed to evaluate current evidence for adding the DTI sequence to the standard diagnostic magnetic resonance imaging (MRI) protocol in pediatric epilepsy. MATERIAL AND METHODS: Rapid and qualitative systematic review (RAE, Rapid Evidence Assessment), aggregating relevant studies from the recent 7 years. The PubMed database was hand searched for records containing terms "tractography AND epilepsy." Only studies referring to children were included; studies were rated using "final quality of evidence." RESULTS: Out of 144 screened records, relevant 101 were aggregated and reviewed. The synthesis was based on 73 studies. Case-control clinical studies were the majority of the material and comprised 43.8% of the material. Low 'confirmability' and low 'applicability' referred to 18 and 17 articles (29.5% and 27.9%), respectively. The sufficient quality of evidence supported performing DTI in temporal lobe epilepsy, malformations of cortical development and prior to a neurosurgery of epilepsy. CONCLUSIONS: The qualitative RAE provides an interim estimate of the clinical relevance of quickly developing diagnostic methods. Based on the critical appraisal of current knowledge, adding the DTI sequence to the standard MRI protocol may be clinically beneficial in selected patient groups with childhood temporal lobe epilepsy or as a part of planning for an epilepsy surgery. PMID- 26851684 TI - An in vivo model of anti-inflammatory activity of subdural dexamethasone following the spinal cord injury. AB - Current therapies to limit the neural tissue destruction following the spinal cord injury are not effective. Our recent studies indicate that the injury to the white matter of the spinal cord results in a severe inflammatory response where macrophages phagocytize damaged myelin and the fluid-filled cavity of injury extends in size with concurrent and irreversible destruction of the surrounding neural tissue over several months. We previously established that a high dose of 4mg/rat of dexamethasone administered for 1 week via subdural infusion remarkably lowers the numbers of infiltrating macrophages leaving large amounts of un phagocytized myelin debris and therefore inhibits the severity of inflammation and related tissue destruction. But this dose was potently toxic to the rats. In the present study the lower doses of dexamethasone, 0.125-2.0mg, were administered via the subdural infusion for 2 weeks after an epidural balloon crush of the mid-thoracic spinal cord. The spinal cord cross-sections were analyzed histologically. Levels of dexamethasone used in the current study had no systemic toxic effect and limited phagocytosis of myelin debris by macrophages in the lesion cavity. The subdural infusion with 0.125-2.0mg dexamethasone over 2 week period did not eliminate the inflammatory process indicating the need for a longer period of infusion to do so. However, this treatment has probably lead to inhibition of the tissue destruction by the severe, prolonged inflammatory process. PMID- 26851685 TI - Comparison of biochemical response between the minimally invasive and standard open posterior lumbar interbody fusion. AB - BACKGROUND: The mini-invasive open posterior lumbar fusion procedure (mini PLIF) procedure is an alternative to standard open procedure (open PLIF) and is intended to reduce surgery-related trauma. The measuring of suitable biochemical factors enables objective comparison of the invasiveness of spinal surgery procedures. METHODS: Prospectively collected data on myoglobin, creatine kinase, interleukin-6, C-reactive protein levels and intensity of low back pain and radicular pain in one-level mini PLIF and open PLIF procedures were analysed. The mini PLIF and the open PLIF groups included 27 and 23 patients, respectively. The collection of blood samples and clinical data were performed preoperatively and on postoperative days 1, 3 and 7. The non-paired t-test was used for statistical evaluation. RESULTS: We did not found any statistically significant differences of myoglobin and creatine kinase levels between the groups. In the open PLIF group the IL-6 levels were significantly higher than in the mini PLIF group on postoperative day 3. CRP levels showed significant lower stress response in favour of the mini PLIF group on postoperative days 3 and 7. Levels of post-op low back pain on day 3 were significantly lower in mini PLIF group. Also intensity of radicular pain on day 1 and 3 were lower also mini PLIF group. CONCLUSION: The extent of myonecrosis was comparable in both techniques. The analysis of the IL-6 and CRP levels showed significantly lower systemic inflammatory response in mini PLIF technique. The mini PLIF technique provides transiently lower postoperative pain levels. PMID- 26851686 TI - Plasma disc decompression compared to physiotherapy for symptomatic contained lumbar disc herniation: A prospective randomized controlled trial. AB - INTRODUCTION: To evaluate clinical outcomes with PDD as compared with patients who underwent to standard physiotherapy intervention. MATERIAL AND METHODS: One hundred-seventy-seven randomly assigned patients with primarily radicular pain associated with a single-level lumbar contained disc herniation were enrolled. Participants received either PDD (89 patients) or conservative physiotherapy care (88 patients). RESULTS: Patients in the PDD group had significantly greater reduction in leg pain scores and significantly improved VAS (p<0.001), Oswestry Disability Index (p<0.05), and 36-Item Short Form, than those in the physiotherapy group at 12 months. On subset analysis, patients achieved even better outcomes after PPD who: were younger, had a shorter period of radiculopathy, of male gender, and lower BMI. Patients with subacute pain reported better outcomes than those with chronic pain in the PDD group. CONCLUSIONS: Patient selection for PDD over physiotherapy favored younger patients who presented with a shorter period of pain symptoms and who had a more favorable body habitus. PMID- 26851687 TI - Management of spinal tumors in neurofibromatosis type 2 patients. AB - OBJECTIVE: We sought to determine clinical characteristics of NF2 patients with spinal lesions and to define when and like the spinal tumors are a major problem in the treatment of patients with NF2. METHODS: The authors retrospectively reviewed the clinical records, neuroimaging studies, and follow-up data of the 34 patients with neurofibromatosis type 2, who were treated at our institution between 1998 and 2014. 23 patients harbored one or multiple spinal tumors. RESULTS: Patients with spinal tumors had a lower age at first symptoms of the disease, a higher number of intracranial meningiomas and non-vestibular schwannomas. 11 patients had one or more intramedullary tumors with MRI characteristics of spinal ependymomas. 22 patients had intradural extramedullary tumors. 7 patients presented with symptomatic spinal tumors on admission or developed symptoms during the follow-up. Only two intramedullary and four extramedullary tumors demonstrated growth in the mean radiological follow-up period of over 6 years. It was found that symptomatic both intra- and extramedullary tumors were associated with younger age at the onset of NF2 related symptoms. 2 patients with intramedullary tumors and 12 patients with extramedullary tumors underwent their tumors resection. In case of symptomatic tumors partial recovery was observed in two patients. CONCLUSION: It seems that close surveillance with MR imaging is a reasonable option for asymptomatic spinal tumors. Nevertheless, intramedullary tumor removal in non-growing and asymptomatic cases may be an option when ABI implantation is considered. Symptomatic tumors and those of documented growth should be eligible for surgical intervention. PMID- 26851688 TI - Surgery for sporadic vestibular schwannoma. Part IV. Predictive factors influencing facial nerve function after surgery. AB - OBJECTIVE: To analyze the impact of various clinical, radiological and perioperative factors that could influence the facial nerve intraoperative disruption risk (CNVII-IDR) and its long-term function (CNVII-LTF) after vestibular schwannoma (VS) surgery. MATERIAL AND METHODS: The study included 212 patients operated on for sporadic VS with no history of previous treatment for VS or CNVII palsy. The mean size of the tumor was 30 mm. Gross (210) or near-total (2) resections were carried out using the retrosigmoid (210) or translabyrinthine (2) approach. Correlation studies and multivariate regression analysis (RA) were performed. RESULTS: In correlation studies, the CNVII-IDR was increased by: headaches and cerebellar ataxia if one of them was the first symptom of the tumor (33% and 29%, respectively, p=0.008); preoperative hydrocephalus (40% vs. 9%, p=0.01), tumor size >3 cm (18% vs. 5%, p<0.01), tumor volume >10 cm(3) (19% vs. 4%, p<0.01), right-sided location 15% vs. 6%, p=0.047), lateral "park-bench" position (19% vs. 5% for supine position, p<0.01) and the procedure order (16% for the first 106 procedures vs. 6% for the last 106 procedures, p<0.05). In RA the tumor volume (p=0.012), side of the tumor (p=0.028) and patient's position during surgery (p=0.016) independently affected the CNVII-IDR. The following factors correlated significantly with satisfactory CNVII-LTF (HB grades I-III): tumor stage 1.0mm(2)). Calcified patches were most abundant in the bulb and least in the common segment (bulb n=7.30+/ 1.08; internal n=4.81+/-1.17; common n=2.56+/-0.56; p=0.0007). Calcified patch circularity decreased with increasing size (<0.1mm(2): 0.77+/-0.01, 0.1-1mm(2): 0.62+/-0.01, >1.0mm(2): 0.51+/-0.02; p=0.0001). A reduced fibrous layer thickness was associated with increased calcium patch size (p<0.0001). CONCLUSIONS: In advanced carotid atherosclerosis, calcification appears to be a heterogeneous and dynamic atherosclerotic plaque component, as indicated by the simultaneous presence of few large stabilizing calcified patches and numerous small calcific patches. Future studies are needed to elucidate the associations of intra-plaque calcification size and distribution with atherothrombotic events. PMID- 26851732 TI - The effects of objectively measured sedentary behavior on all-cause mortality in a national sample of adults with diabetes. AB - BACKGROUND: Diabetes is a highly prevalent chronic disease that has been increasing globally and is the seventh leading cause of death in the United States. Sedentary behavior is associated with increased risk of diabetes and is unfavorably related to all-cause mortality, but there are limited studies examining the sedentary-mortality relationship among those with diabetes, which was the purpose of this study. METHODS: Using data from the 2003-2006 NHANES, 712 adult participants with evidence of diabetes had complete data on the study variables. A multivariable Cox proportional hazard model was used to examine the association between objectively measured sedentary behavior and all-cause mortality among this diabetic sample. RESULTS: Results showed that for every 60min/day increase in sedentary behavior, independent of moderate-to-vigorous physical activity (MVPA) and other covariates, adults with diabetes had a 13% increased risk of all-cause mortality (HRadjusted=1.13; 95% CI=1.03-1.24; P=0.01). However, after adjusting for total physical activity (light and MVPA), sedentary behavior was no longer associated with mortality risk (HRadjusted=1.04; 95% CI=0.92-1.16; P=0.46). CONCLUSION: Among those with diabetes, sedentary behavior may not have increased mortality risk independent of total physical activity behavior. PMID- 26851731 TI - Reversal of phenotypes of cellular senescence by pan-mTOR inhibition. AB - Cellular senescence, a state of essentially irreversible proliferation arrest, serves as a potent tumour suppressor mechanism. However, accumulation of senescent cells with chronological age is likely to contribute to loss of tissue and organ function and organismal aging. A crucial biochemical modulator of aging is mTOR; here, we have addressed the question of whether acute mTORC inhibition in near-senescent cells can modify phenotypes of senescence. We show that acute short term treatment of human skin fibroblasts with low dose ATP mimetic pan mTORC inhibitor AZD8055 leads to reversal of many phenotypes that develop as cells near replicative senescence, including reduction in cell size and granularity, loss of SA-beta-gal staining and reacquisition of fibroblastic spindle morphology. AZD8055 treatment also induced rearrangement of the actin cytoskeleton, providing a possible mechanism of action for the observed rejuvenation. Importantly, short-term drug exposure had no detrimental effects on cell proliferation control across the life-course of the fibroblasts. Our findings suggest that combined inhibition of both mTORC1 and mTORC2 may provide a promising strategy to reverse the development of senescence-associated features in near-senescent cells. PMID- 26851733 TI - Genetic analysis of attenuation markers of cold-adapted X-31 influenza live vaccine donor strain. AB - Cold-adapted live attenuated influenza vaccines (CAIVs) have been considered as a safe prophylactic measure to prevent influenza virus infections. The safety of a CAIV depends largely on genetic markers that confer specific attenuation phenotypes. Previous studies with other CAIVs reported that polymerase genes were primarily responsible for the attenuation. Here, we analyzed the genetic mutations and their phenotypic contribution in the X-31 ca strain, a recently developed alternative CAIV donor strain. During the cold-adaptation of its parental X-31 virus, various numbers of sequence changes were accumulated in all six internal genes. Phenotypic analysis with single-gene and multiple-gene reassortant viruses suggests that NP gene makes the largest contribution to the cold-adapted (ca) and temperature-sensitive (ts) characters, while the remaining other internal genes also impart attenuation characters with varying degrees. A balanced contribution of all internal genes to the attenuation suggests that X-31 ca could serve as an ideal master donor strain for CAIVs preventing influenza epidemics and pandemics. PMID- 26851734 TI - Changing the default to promote influenza vaccination among health care workers. AB - BACKGROUND: The prevention of health care acquired infections is an important objective for patient safety and infection control in all health care settings. Influenza vaccination uptake among health care workers (HCWs) is the most effective method to prevent transmission to patients, but vaccination coverage rates are low among HCWs. Several educational campaigns have been developed to increase the influenza vaccination coverage rates of HCWs, but showed only small effects. The aim of this study was to test an opt-out strategy in promoting uptake among HCWs in a tertiary care center for patients with complex chronic organ failure. METHODS: HCWs were randomly assigned to one of two conditions. In the opt-out condition (N=61), participants received an e-mail with a pre scheduled appointment for influenza vaccination, which could be changed or canceled. In the opt-in condition (N=61), participants received an e-mail explaining that they had to schedule an appointment if they wanted to get vaccinated. RESULTS: The findings show no statistically detectable effect of condition on being vaccinated against influenza. However, HCWs in the opt-out condition were more likely to have an appointment for influenza vaccination, which in turn increased the probability of getting vaccinated. CONCLUSION: To change the default to promote influenza vaccination among HCWs might be an easy and cost-effective alternative to the complex vaccination campaigns that have been proposed in recent years. PMID- 26851735 TI - Hepatic transcriptomic and metabolic responses of hybrid striped bass (Morone saxatilis*Morone chrysops) to acute and chronic hypoxic insult. AB - Striped bass (Morone saxatilis), white bass (Morone chrysops), and their hybrid are an important group of fish prized for recreational angling in the United States, and there and abroad as a high-value farmed fish. Regardless of habitat, it is not uncommon for fish of the genus Morone to encounter and cope with conditions of scarce oxygen availability. Previously, we determined that hybrid striped bass reared under conditions of chronic hypoxia exhibited reduced feed intake, lower lipid and nutrient retention, and poor growth. To better understand the molecular mechanisms governing these phenotypes, in the present study, we examined the transcriptomic profiles of hepatic tissue in hybrid striped bass exposed to chronic hypoxia (90days at 25% oxygen saturation) and acute hypoxia (6h at 25% oxygen saturation). Using high-throughput RNA-seq, we found that over 1400 genes were differentially expressed under disparate oxygen conditions, with the vast majority of transcriptional changes occurring in the acute hypoxia treatment. Gene pathway and bioenergetics analyses revealed hypoxia-mediated perturbation of genes and gene networks related to lipid metabolism, cell death, and changes in hepatic mitochondrial content and cellular respiration. This study offers a more comprehensive view of the temporal and tissue-specific transcriptional changes that occur during hypoxia, and reveals new and shared mechanisms of hypoxia tolerance in teleosts. PMID- 26851736 TI - Synthesis and pharmacological characterization of novel xanthine carboxylate amides as A2A adenosine receptor ligands exhibiting bronchospasmolytic activity. AB - The carboxylate amides of 8-phenyl-1,3-dimethylxanthine described herein represent a new series of selective ligands of the adenosine A2A receptors exhibiting bronchospasmolytic activity. The effects of location of 8-phenyl substitutions on the adenosine receptor (AR) binding affinities of the newly synthesized xanthines have also been studied. The compounds displayed moderate to potent binding affinities toward various adenosine receptor subtypes when evaluated through radioligand binding studies. However, most of the compounds showed the maximum affinity for the A2A subtype, some with high selectivity versus all other subtypes. Xanthine carboxylate amide 13b with a diethylaminoethylamino moiety at the para-position of the 8-phenylxanthine scaffold was identified as the most potent A2A adenosine receptor ligand with Ki=0.06MUM. Similarly potent and highly A2A-selective are the isovanillin derivatives 16a and 16d. In addition, the newly synthesized xanthine derivatives showed good in vivo bronchospasmolytic activity when tested in guinea pigs. PMID- 26851737 TI - One-pot synthesis of tetrazole-1,2,5,6-tetrahydronicotinonitriles and cholinesterase inhibition: Probing the plausible reaction mechanism via computational studies. AB - In the present study, one-pot synthesis of 1H-tetrazole linked 1,2,5,6 tetrahydronicotinonitriles under solvent-free conditions have been carried out in the presence of tetra-n-butyl ammonium fluoride trihydrated (TBAF) as catalyst and solvent. Computational studies have been conducted to elaborate two plausible mechanistic pathways of this one-pot reaction. Moreover, the synthesized compounds were screened for cholinesterases (acetylcholinesterase and butyrylcholinesterase) inhibition which are consider to be major malefactors of Alzheimer's disease (AD) to find lead compounds for further research in AD therapy. PMID- 26851738 TI - Phenotypic characteristics and genotypic correlation between Salmonella isolates from a slaughterhouse and retail markets in Yangzhou, China. AB - An epidemiological investigation of Salmonella spp. in pig and pork samples from one slaughterhouse and its downstream retail markets in Yangzhou, Jiangsu Province, China, was conducted from October 2013 to March 2014. A total of 71.8% (155/216) and 70.9% (78/110), respectively, of the slaughterhouse and retail market samples were recovered positive for Salmonella. All Salmonella isolates were characterized using serotyping, antimicrobial resistance detection, multilocus sequence typing (MLST), and pulsed-field gel electrophoresis (PFGE). Seven serotypes were shared by isolates from the two sources, with the most common serotypes being Salmonella Derby, Typhimurium, and Uganda. Antimicrobial sensitivity testing revealed that the highest antimicrobial resistance rate was against tetracycline (49.7% and 37.2% in isolates from the slaughterhouse and retail market, respectively) with many multidrug-resistant (MDR) isolates in both sources. MLST analysis showed that eight sequence type (ST) patterns were shared, and ST40 occupied an absolute superiority among isolates from both sources. PFGE permitted the resolution of XbaI macrorestriction fragments of the selected 31 Salmonella Derby and 19 Salmonella Typhimurium into 30 and 10 distinct pulsotypes, displaying the high similarity between the isolates from the two sources. Our findings indicated that Salmonella isolates from a slaughterhouse and its downstream retail markets were phenotypically and genetically homologous. Additionally, Salmonella may propagate along the slaughter line and pork production chain from the slaughterhouse to retail markets. PMID- 26851739 TI - Flow-Related Aneurysm within Glioblastoma: A Case Report and Review of Literature. AB - BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, with a median survival of 13 months despite surgery and chemoradiation. GBMs are often hypervascular tumors caused by abnormal oversecretion of growth factors such as vascular endothelial growth factor. These angiogenic factors are hypothesized to promote increased blood flow and possibly secondary changes to arterial walls, thus facilitating the formation of flow related aneurysms. CASE DESCRIPTION: A 59-year-old woman presented with headaches, confusion, nausea and emesis. Computed tomography and magnetic resonance imaging revealed a hypervascular lesion, likely high-grade glioma, in the right frontal lobe, with a dilated vessel within the tumor. Cerebral angiography demonstrated a flow-related aneurysm on the right frontopolar artery supplying the tumor. The aneurysm was embolized with coils and the patient later underwent craniotomy for near total resection of the lesion without complications. Final pathology returned GBM with dilated vessels noted. CONCLUSIONS: Hypervascular lesions, such as GBMs, may be associated with flow related aneurysms on feeding arteries, but aneurysms within the gross tumor are unusual. Although rare, this finding needs to be recognized on preoperative imaging before tumor resection to prevent potentially catastrophic intraoperative complications. PMID- 26851740 TI - Decompressive Craniectomy in Conjunction With Evacuation of Intracranial Hemorrhagic Lesions Is Associated With Worse Outcomes in Elderly Patients With Traumatic Brain Injury: A Propensity Score Analysis. AB - BACKGROUND: When it comes to evacuating intracranial hemorrhagic lesions in patients with traumatic brain injury (TBI), neurosurgeons perform either a craniotomy or a decompressive craniectomy (DC). The aim of the present study was to estimate the impact of DC on outcomes in elderly patients. METHODS: This retrospective cohort study, conducted in a neurosurgical institute in Japan from April 2009 to June 2014, included 91 consecutive patients with TBI (aged 60 years or older) who underwent evacuation of intracranial hemorrhagic lesions. Patients were divided into 2 groups: craniotomy only or DC. We set the primary endpoint as an unfavorable outcome (death or vegetative state), as evaluated on the Glasgow Outcome Scale at 6 months after injury. The secondary endpoints included existence of delayed hemorrhage and occurrence of hydrocephalus requiring shunt placement. The inverse probability of treatment weighting method was used to develop a propensity model to adjust for baseline imbalances between groups. RESULTS: The DC group exhibited greater severity both in clinical and computed tomography findings according to baseline characteristics. After we adjusted for these differences by inverse probability of treatment weighting using the propensity score, DC was significantly associated with unfavorable outcomes (adjusted odds ratio, 8.00; 95% confidential interval, 2.30-27.84; P = 0.002) and delayed hemorrhage (adjusted odds ratio, 13.42; 95% confidential interval, 1.52 118.89; P = 0.022). There was no significant difference in the occurrence of hydrocephalus requiring shunt placement. CONCLUSIONS: DC in conjunction with evacuation of intracranial hemorrhagic lesions was associated with worse functional outcome in elderly patients with TBI. PMID- 26851741 TI - Clinically Diagnosed Postoperative Venous Thromboembolism in a Neurosurgery Practice in Nigeria. AB - INTRODUCTION: Postoperative venous thromboembolism (VTE) is a major surgical complication, fraught with high case fatality rate, to which neurosurgical patients are particularly prone. There is dearth of data on this problem in the neurosurgical literature from sub-Saharan Africa. MATERIALS AND METHODS: A 6-year prospective descriptive study of postoperative VTE in a neurosurgeon's clinical practice in Nigeria is hereby presented. The clinical case of a fatal, postmortem confirmed post craniotomy VTE also is annotated. RESULTS: There were 10 cases of clinically diagnosed neurosurgical postoperative VTE, representing 2.4% of the surgical patients population. The cases were diagnosed from clinical impressions supplemented with laboratory investigations like the Doppler ultrasonography with B-mode imaging of the deep veins of the lower extremities, and chest computed tomographic angiography. Six of these 10 cases died, a case fatality rate of 60%. Meningiomas were the intracranial tumours operated on in 60% of the cases. CONCLUSIONS: Postoperative venous thromboembolism has a very high case fatality rate among these neurosurgical patients. There is need for continuing surveillance of this problem, as well as a heightened vigilance to prevent and treat it in our neurosurgical patient populations. PMID- 26851742 TI - Atypical Association of Ethmoidal Encephalocele and Hydrocephalus in an Adult Patient with Autosomal-Dominant Osteopetrosis Type I (ADO-I): A Case Report. AB - BACKGROUND: Osteopetroses are a heterogeneous group of heritable disorders characterized by increased bone density as the result of defective osteoclast mediated bone resorption. The autosomal-dominant osteopetrosis type I (ADO-I) is defined by the presence of osteosclerosis involving mainly the skull bones, variably associated with compression of the foramina of cranial nerves and vascular structures, hypertelorism, exophthalmos, and less commonly with hydrocephalus, pseudotumor, and Chiari malformation type I. CASE DESCRIPTION: We describe an adult patient with ADO-I presenting with an atypical association of clinical manifestations that required a tailored management. On admission, the patient complained about chronic headache, recurrent sinusitis, and postnasal drip. Findings of the examination didn't show clear signs of increased intracranial pressure, whereas imaging studies revealed thickening of the skull bones and an unexpected fistula associated with anterior ethmoidal meningoencephalocele. Some days after endoscopic transnasal closure of the fistula, a severe hypertensive hydrocephalus developed, which required a prompt ventriculoperitoneal shunt placement, complicated by a diffuse subarachnoid hemorrhage. The 6-month follow-up showed complete recovery. CONCLUSIONS: After reviewing the literature, we can confirm that ours was the second case of an adult ADO-I patient associated with anterior ethmoidal meningoencephalocele, the first one needing a combined treatment of the encephalocele and hydrocephalus. Because ADO-I is a rare disease with a wide spectrum of clinical manifestations, our case can represent a prototype for the future management of similar cases. PMID- 26851743 TI - Cisternostomy for Traumatic Brain Injury: Pathophysiologic Mechanisms and Surgical Technical Notes. AB - OBJECTIVE: Traumatic brain injury (TBI) is one of the major challenges in health care, representing the third most frequent cause of death. Current optimal management is based on a progressive, target-driven approach combining both medical and surgical treatment strategies. Here we describe cisternostomy, an emerging surgical treatment for the treatment of TBI. METHODS: Cisternostomy is a novel technique that incorporates knowledge of skull base and microvascular surgery. By opening the brain cisterns to atmospheric pressure, the technique could decrease the intracranial pressure due to a backshift of the cerebrospinal fluid (CSF) from the swollen brain to the cisterns through the Virchow-Robin spaces. RESULTS: An increasing number of evidence has demonstrated a paravascular pathway that facilitates CSF flow from the subarachnoid space through the brain parenchyma. This network of paravascular channels, termed as the "glymphatic" pathway, reduces considerably its activity after TBI, thus participating in the development of brain edema formation. Cisternostomy, by opening the brain cisterns to atmospheric pressure, could decrease the intracerebral pressure due to a backshift of CSF through the Virchow-Robin spaces. CONCLUSIONS: In the current common practice, the surgical measures for TBI include external ventricular drainage insertion and decompressive craniectomy. There is evidence that both of these measures reduce intracranial pressure but the effect on the outcome, particularly in the long term, is equivocal. A new line of evidence supports cisternostomy as an emerging surgical treatment for TBI. PMID- 26851744 TI - Steroids and Spinal Cord Injury-A Global Dilemma. PMID- 26851745 TI - Intraoperative Multi-Information-Guided Resection of Dominant-Sided Insular Gliomas in a 3-T Intraoperative Magnetic Resonance Imaging Integrated Neurosurgical Suite. AB - OBJECTIVE: To evaluate the clinical application of 3-T intraoperative magnetic resonance imaging (iMRI), awake craniotomy, multimodal functional mapping, and intraoperative neurophysiologic monitoring (IONM) for resection of dominant-sided insular gliomas. METHODS: From March 2011 to June 2013, 30 gliomas involving the dominant insular lobe were resected in the IMRIS 3.0-T iMRI integrated neurosurgical suite. For 20 patients, awake craniotomy with cortical electrical stimulation mapping was performed to locate the language areas. For 10 patients who were not suitable for awake surgery, general anesthesia and functional navigation were performed. Diffusion tensor imaging tractography-based navigation, continuous motor evoked potential monitoring, and subcortical electrical stimulation mapping were applied to localize and monitor the motor pathway in all cases. iMRI was used to assess the extent of resection. The results of intraoperative imaging, IONM, and the surgical consequences were analyzed. RESULTS: Intraoperative imaging revealed residual tumor in 26 cases and led to further resection in 9 cases. As a result, the median extent of resection was increased from 90% to 93% (P = 0.008) in all cases, and from 88% to 92% (P = 0.018) in low-grade gliomas. The use of iMRI also resulted in an increase in the percentage of gross and near total resection from 53% to 77% (P = 0.016). The rates of permanent language and motor deficits resulting from tumor removal were 11% and 7.1%, respectively. CONCLUSIONS: The combination of iMRI, awake craniotomy, multimodal brain mapping, and IONM tailored for each patient permits the maximal safe resection of dominant-sided insular glioma. PMID- 26851746 TI - Spinal Cervical Meningiomas: The Challenge Posed by Ventral Location. AB - OBJECTIVE: To evaluate the incidence, clinical presentation, operative techniques, and long-term outcome of spinal cervical meningiomas after surgery. METHODS: Twenty-two patients harboring spinal meningiomas on cervical region were treated between 2004 and 2014 in our department. Diagnosis was made via magnetic resonance imaging and confirmed histologically. Microsurgical resection was performed through different surgical approaches according to location of the tumor. To remove the tumor, the posterior, far-lateral, and combined approaches were used, respectively, in 13 patients (56%), 8 patients (35%), and 2 patients (9%). RESULTS: The mean follow-up was 40 +/- 26.5 months. The most common site of dural attachment of meningioma was ventral or ventrolateral to the spinal cord. Macroscopic resection was considered complete in 55% of cases. Neurologic improvement was observed in 60% of cases. The rate of operative mortality and morbidity was high (26.5%). Five patients underwent postoperative radiotherapy according to the actual recommendation, and the overall recurrence rate was 9%. CONCLUSIONS: Spinal meningiomas are benign tumors for which advances in imaging tools and microsurgical techniques have yielded better results. The goal of surgery should be the total resection, which significantly decreases the risk of recurrence with an acceptable morbidity. Cervical locations represent a challenge particularly for ventro and ventrolaterally located tumors. Despite the difficulty of performing a complete resection, the results obtained in this work advocate for the use of the far-lateral approach to manage meningiomas locate anterior to the neural axis. PMID- 26851747 TI - Organizational context associated with time spent evaluating language and cognitive-communicative impairments in skilled nursing facilities: Survey results within an implementation science framework. AB - BACKGROUND: The Consolidated Framework for Implementation Research (CFIR) was developed to merge research and practice in healthcare by accounting for the many elements that influence evidence-based treatment implementation. These include characteristics of the individuals involved, features of the treatment itself, and aspects of the organizational culture where the treatment is being provided. AIMS: The purpose of this study was to apply the CFIR to a measurement of current practice patterns of speech-language pathologists (SLPs) working in the skilled nursing facility (SNF) environment. In an effort to inform future evidence-based practice implementation interventions, research questions addressed current practice patterns, clinician treatment use and preferences, and perceptions of the organizational context including leadership, resources, and other staff. METHODS AND PROCEDURES: Surveys were mailed to each SLP working in a SNF in the state of Michigan. Participants (N=77, 19% response rate) completed a survey mapping on to CFIR components impacting evidence-based practice implementation. Quantitative descriptive and nonparametric correlational analyses were completed. OUTCOMES AND RESULTS: Use of evidence-based treatments by SLPs in SNFs was highly variable. Negative correlations between treating speech and voice disorders and treating swallowing disorders (rs=-.35, p<.01), evaluating language and cognitive communicative disorders and treating swallowing disorders (rs=-.30, p<.01), treating language and cognitive-communicative disorders and treating swallowing disorders (rs=-.67, p<.01), and evaluating swallowing disorders and treating language and cognitive-communicative disorders (rs=-.37, p<.01) were noted. A positive correlation between the SLPs' perception of organizational context and time spent evaluating language and other cognitive-communicative disorders (rs=.27, p<.05) was also present. CONCLUSIONS: Associative data suggest that the more an SLP in the SNF evaluates and treats swallowing disorders, the less he or she will evaluate speech, voice, language or other cognitive-communicative disorders. Further, SLPs in this sample spent more time evaluating language and cognitive-communicative impairments if they perceived their organizational context in a more positive way. The CFIR may guide treatment and implementation research to increase the uptake of evidence-based practices for SLPs working in the SNF setting. PMID- 26851748 TI - The structure of obsessive compulsive symptoms and beliefs: A correspondence and biplot analysis. AB - Research has suggested that obsessive-compulsive (OC) beliefs are differentially predictive of OC symptom dimensions. One additional way in which beliefs and symptoms may be related is by severity; that is, the role of beliefs may vary as a function of symptom severity. In order to evaluate this possibility, correspondence analysis with biplot was applied to evaluate the association between OC beliefs and OC symptom severity across three subsamples, individuals with obsessive-compulsive disorder (OCD; N=398), individuals with anxiety disorders (N=104), and undergraduate students (N=285). To do so, we generated five row categories of symptom severity and six columns based on the Obsessive Compulsive Beliefs Questionnaire (OBQ) for three subsamples. Unlike factor analyses of inter-variable correlations (or covariances), the CA-biplot paradigm calibrates simultaneously row and column information and estimates dimensional coordinates (analogous to factor loadings) separately for rows and columns. We used the first two dimensions from each subsample because they accounted for most variance (on average 89%) so as to construct a hypothetical plane with them. Then, we visually inspected associations among five severity categories (rows) and six OBQ subscales (columns) in the plane and also calculated their correlations. The visual configurations and numerical correlations were consistent across three subsamples, indicating that inflated responsibility was significantly associated with OC symptoms, but only for those with the least severe symptoms. Importance and control of thoughts were associated with OC symptoms across all levels of symptom severity. The implications of these findings for the cognitive model of OCD are considered. PMID- 26851749 TI - Does cyberchondria overlap with health anxiety and obsessive-compulsive symptoms? An examination of latent structure and scale interrelations. AB - Searching for medical information online is a widespread activity that increases distress for many individuals. Researchers have speculated that this phenomenon, referred to as cyberchondria, overlaps substantially with both health anxiety and obsessive-compulsive symptoms. This study sought to examine: (1) the distinguishability of cyberchondria from health anxiety and obsessive-compulsive symptoms and (2) the components of health anxiety and obsessive-compulsive symptoms that cluster most strongly with cyberchondria. The sample consisted of community adults in the United States with no current reported medical problems (N=375). Results from confirmatory factor analyses (CFAs) support the idea that cyberchondria is distinct from, yet related to, health anxiety and obsessive compulsive symptoms. Results from zero-order correlations and regression analyses suggest that cyberchondria clusters with the affective (health worry) component of health anxiety. Regression results diverged from prior findings, as obsessive compulsive symptoms did not share associations with cyberchondria after accounting for negative affect and health anxiety. The present results indicate that cyberchondria is possibly discernible from both health anxiety and obsessive compulsive symptoms, while also providing insight into areas of potential overlap. PMID- 26851751 TI - Cancer among patients with type 2 diabetes mellitus: A population-based cohort study in northeastern Italy. AB - Diabetes mellitus (DM) is associated with an elevated risk of cancer. The aim of this study was to assess cancer risk and survival in individuals with type 2 DM (T2DM) in Friuli Venezia Giulia, Italy. A retrospective population-based cohort study of 32,247 T2DM patients aged 40-84 years was conducted through a record linkage of local healthcare databases and cancer registry for the period 2002 2009. Standardized incidence ratios (SIRs) with 95% confidence intervals (95%CIs) and 5-year survival probabilities after T2DM and cancer diagnosis were computed. The SIRs for all cancers (n=2069) was 1.28 (95%CI: 1.23-1.34). The highest SIRs were observed for cancers of the liver, female genital organs, small intestine, and pancreas. After 3 years from T2DM diagnosis, a reduced risk of prostate cancer (SIR=0.73, 95%CI: 0.54-0.96) was found in men aged 65-74 years, and a higher risk for breast cancer (SIR=1.24, 95%CI: 1.00-1.52) was found among T2DM female patients. The overall 5-year survival after T2DM was 88.7%. Furthermore, T2DM appeared to have a negative effect on survival of women with breast cancer. This population-based study confirmed that T2DM patients are at increased risk of several cancers, and of premature death in women with breast cancer. PMID- 26851752 TI - The epidemic of oesophageal carcinoma: Where are we now? AB - Since the early 1970s, the incidence of oesophageal adenocarcinoma has increased dramatically in most Western populations. In contrast, the incidence of oesophageal squamous-cell carcinoma has decreased in these same populations. Epidemiological studies conducted over the past decade have provided great insights into the etiology of oesophageal cancer. These studies have identified gastro-oesophageal reflux disease, obesity and cigarette smoking as risk factors for oesophageal adenocarcinoma, while use of nonsteroidal anti-inflammatory drugs and infection with Helicobacter pylori are associated with reduced risk of oesophageal adenocarcinoma. For oesophageal squamous-cell carcinoma, alcohol and cigarette smoking are the two major risk factors underlying most cases. This review combines a synthesis of these studies with an analysis of data from the United States National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program to discuss the change in incidence of oesophageal cancer and summarize current knowledge of risk factors. PMID- 26851750 TI - The association between socioeconomic status and tumour stage at diagnosis of ovarian cancer: A pooled analysis of 18 case-control studies. AB - PURPOSE: Socioeconomic status (SES) is a known predictor of survival for several cancers and it has been suggested that SES differences affecting tumour stage at diagnosis may be the most important explanatory factor for this. However, only a limited number of studies have investigated SES differences in tumour stage at diagnosis of ovarian cancer. In a pooled analysis, we investigated whether SES as represented by level of education is predictive for advanced tumour stage at diagnosis of ovarian cancer, overall and by histotype. The effect of cigarette smoking and body mass index (BMI) on the association was also evaluated. METHODS: From 18 case-control studies, we obtained information on 10,601 women diagnosed with epithelial ovarian cancer. Study specific odds ratios (ORs) with corresponding 95% confidence intervals (CI) were obtained from logistic regression models and combined into a pooled odds ratio (pOR) using a random effects model. RESULTS: Overall, women who completed <=high school had an increased risk of advanced tumour stage at diagnosis compared with women who completed >high school (pOR 1.15; 95% CI 1.03-1.28). The risk estimates for the different histotypes of ovarian cancer resembled that observed for ovarian cancers combined but did not reach statistical significance. Our results were unchanged when we included BMI and cigarette smoking. CONCLUSION: Lower level of education was associated with an increased risk of advanced tumour stage at diagnosis of ovarian cancer. The observed socioeconomic difference in stage at diagnosis of ovarian cancer calls for further studies on how to reduce this diagnostic delay. PMID- 26851753 TI - 5-Hydroxymethylcytosine expression is associated with poor survival in cervical squamous cell carcinoma. AB - OBJECTIVE: Deoxyribonucleic acid methylation is an important epigenetic modification that is frequently altered in cancer. Recent reports showed that the level of 5-hydroxymethylcytosine was altered in various types of cancers. The influence of deoxyribonucleic acid methylation in cervical squamous cell carcinoma is not fully understood. In this study, we investigated 5 hydroxymethylcytosine and ten-eleven translocation expression in cervical squamous cell carcinoma and whether they are associated with poor survival in cervical squamous cell carcinoma. METHODS: We detected the expression of 5 hydroxymethylcytosine, 5-methylcytosine and TET1/2/3 in 140 patients with cervical squamous cell carcinoma and 40 patients with normal cervical tissues by immunohistochemistry. We assessed the prognostic values of 5 hydroxymethylcytosine, 5-methylcytosine and TET2 in the clinical outcome of cervical squamous cell carcinoma. RESULTS: Expression of 5-hydroxymethylcytosine was significantly decreased in cervical squamous cell carcinoma compared with normal cervix tissues. In contrast, 5-methylcytosine expression was significantly increased in cervical squamous cell carcinoma compared with normal cervix tissues. Moreover, expression of TET2, but not TET1 and TET3, was decreased in cervical squamous cell carcinoma. Our study showed that the decreased level of 5 hydroxymethylcytosine predicts poor prognosis of cervical squamous cell carcinoma patients. The expression of 5-hydroxymethylcytosine was an independent prognostic factor for both disease-free and overall survival of cervical squamous cell carcinoma patients. CONCLUSIONS: In cervical squamous cell carcinoma, less aggressive tumor behavior was correlated with 5-hydroxymethylcytosine and TET2. Our data indicated that 5-hydroxymethylcytosine may become a prognostic marker for cervical squamous cell carcinoma and the decreased expression of TET2 may be an underlying mechanism for decreased 5-hmC in cervical squamous cell carcinoma. PMID- 26851755 TI - Why neurons mix: high dimensionality for higher cognition. AB - Neurons often respond to diverse combinations of task-relevant variables. This form of mixed selectivity plays an important computational role which is related to the dimensionality of the neural representations: high-dimensional representations with mixed selectivity allow a simple linear readout to generate a huge number of different potential responses. In contrast, neural representations based on highly specialized neurons are low dimensional and they preclude a linear readout from generating several responses that depend on multiple task-relevant variables. Here we review the conceptual and theoretical framework that explains the importance of mixed selectivity and the experimental evidence that recorded neural representations are high-dimensional. We end by discussing the implications for the design of future experiments. PMID- 26851754 TI - Diversity in treatment modalities of Stage II/III urothelial cancer in Japan: sub analysis of the multi-institutional national database of the Japanese Urological Association. AB - OBJECTIVE: We aimed to survey treatment modalities for the patients with Stage II/III urothelial cancer in Japan. METHODS: We used the multi-institutional national database of the Japanese Urological Association from 348 Japanese institutions, in which a total of 3707 patients with muscle-invasive bladder cancer and 1538 with upper urinary tract urothelial carcinoma were registered in 2008 and 2011, respectively. Primary treatment was classified as surgery alone, surgery with chemotherapy, surgery with radiation, radiation alone, chemotherapy alone, combination of radiation and chemotherapy and observation. Overall and cancer-specific survivals were examined using the Kaplan-Meier method, and survival in the subgroups was analyzed using the log-rank test. RESULTS: In Stage II/III bladder cancer patients, 49.7% of those were treated with radical operation and 22.3% received observation only. A total 97.2% of Stage II/III upper urinary tract urothelial carcinoma patients treated with radical surgery. A total 30.4% of Stage II/III bladder cancer patients received chemotherapy. Majority of the patients received cisplatin-based regimen, however, regimens of chemotherapy was rich in variety up to 13 regimens. Chemotherapy regimens for the patients with upper urinary tract urothelial carcinoma were also various up to eight regimens. Overall and cancer-specific survivals were statistically significantly stratified according to the clinical stage. The upper urinary tract urothelial carcinoma patients diagnosed with clinical stage T3 had significantly poor prognosis compared with those diagnosed with clinical stage T2. CONCLUSIONS: This study demonstrated the variety of treatments used for Japanese patients with Stage II/III urothelial cancer. Treatment standardization for these entities may be necessary. PMID- 26851757 TI - Assessing future drought impacts on yields based on historical irrigation reaction to drought for four major crops in Kansas. AB - Evaluation of how historical irrigation reactions can adapt to future drought is indispensable to irrigation policy, however, such reactions are poorly quantified. In this paper, county-level irrigation data for maize, soybean, grain sorghum, and wheat crops in Kansas were compiled. Statistical models were developed to quantify changes of irrigation and yields in response to drought for each crop. These were then used to evaluate the ability of current irrigation to cope with future drought impacts on each crop based on an ensemble Palmer Drought Severity Index (PDSI) prediction under the Representative Concentration Pathways 4.5 scenario. Results indicate that irrigation in response to drought varies by crop; approximately 10 to 13% additional irrigation was applied when PDSI was reduced by one unit for maize, soybean, and grain sorghum. However, the irrigation reaction for wheat exhibits a large uncertainty, indicating a weaker irrigation reaction. Analysis of future climate conditions indicates that maize, soybean, and grain sorghum yields would decrease 2.2-12.4% at the state level despite additional irrigation application induced by drought (which was expected to increase 5.1-19.0%), suggesting that future drought will exceed the range that historical irrigation reactions can adapt to. In contrast, a lower reduction ( 0.99 to -0.63%) was estimated for wheat yields because wetter climate was projected in the central section of the study area. Expanding wheat areas may be helpful in avoiding future drought risks for Kansas agriculture. PMID- 26851756 TI - Development and application of freshwater sediment-toxicity benchmarks for currently used pesticides. AB - Sediment-toxicity benchmarks are needed to interpret the biological significance of currently used pesticides detected in whole sediments. Two types of freshwater sediment benchmarks for pesticides were developed using spiked-sediment bioassay (SSB) data from the literature. These benchmarks can be used to interpret sediment-toxicity data or to assess the potential toxicity of pesticides in whole sediment. The Likely Effect Benchmark (LEB) defines a pesticide concentration in whole sediment above which there is a high probability of adverse effects on benthic invertebrates, and the Threshold Effect Benchmark (TEB) defines a concentration below which adverse effects are unlikely. For compounds without available SSBs, benchmarks were estimated using equilibrium partitioning (EqP). When a sediment sample contains a pesticide mixture, benchmark quotients can be summed for all detected pesticides to produce an indicator of potential toxicity for that mixture. Benchmarks were developed for 48 pesticide compounds using SSB data and 81 compounds using the EqP approach. In an example application, data for pesticides measured in sediment from 197 streams across the United States were evaluated using these benchmarks, and compared to measured toxicity from whole sediment toxicity tests conducted with the amphipod Hyalella azteca (28-d exposures) and the midge Chironomus dilutus (10-d exposures). Amphipod survival, weight, and biomass were significantly and inversely related to summed benchmark quotients, whereas midge survival, weight, and biomass showed no relationship to benchmarks. Samples with LEB exceedances were rare (n=3), but all were toxic to amphipods (i.e., significantly different from control). Significant toxicity to amphipods was observed for 72% of samples exceeding one or more TEBs, compared to 18% of samples below all TEBs. Factors affecting toxicity below TEBs may include the presence of contaminants other than pesticides, physical/chemical characteristics of sediment, and uncertainty in TEB values. Additional evaluations of benchmarks in relation to sediment chemistry and toxicity are ongoing. PMID- 26851758 TI - Assessing redox potential of a native tree from the Brazilian Atlantic Rainforest: a successful evaluation of oxidative stress associated to a new power generation source of an oil refinery. AB - The antioxidant responses in saplings of Tibouchina pulchra (a native tree from the Brazilian Atlantic Rainforest) exposed around an oil refinery in the city of Cubatao (SE Brazil), varied during the exchange of its power generation source, from boilers fueled with oil to a thermoelectric fueled with natural gas. The redox potential changed in response to an interaction of air pollution and meteorological parameters, indicating that the pro-oxidant/antioxidant balance was not reached after the exchange of the power generation system. The gain in environmental quality in the region was not achieved as expected due the technological modernization, at least relative to oxidative stressors. These conclusions were based on results of analyses of enzymatic antioxidants: superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR); non-enzymatic antioxidants: reduced, oxidized and total ascorbic acid (AsA, DHA, totAA) and glutathione (GSH, GSSG, totG), their redox state (AsA/totAA and GSH/totG) and an indicator of lipid peroxidation (MDA). We also applied exploratory multivariate statistics in order to verify if the temporal sequence of changes in the plant redox capacity coincided with changes in the profile of air pollution, climatic conditions or with their interactions and if the environmental benefits that would supposedly be promoted by the mentioned exchange of power generation system were achieved in the region. PMID- 26851759 TI - Effects of virtual water flow on regional water resources stress: A case study of grain in China. AB - Scarcity of water resources is one of the major challenges in the world, particularly for the main water consumer, agriculture. Virtual water flow (VWF) promotes water redistribution geographically and provides a new solution for resolving regional water shortage and improving water use efficiency in the world. Virtual water transfer among regions will have a significant influence on the water systems in both grain export and import regions. In order to assess the impacts of VWF related grain transfer on regional water resources conditions, the study takes mainland China as study area for a comprehensive evaluation of virtual water flow on regional water resources stress. Results show that Northeast China and Huang-Huai-Hai region are the major grain production regions as well as the major virtual water export regions. National water savings related to grain VWF was about 58Gm(3), with 48Gm(3) blue water and 10Gm(3) green water. VWF changes the original water distribution and has a significant effect on water resources in both virtual water import and export regions. Grain VWF significantly increased water stress in grain export regions and alleviated water stress in grain import regions. Water stress index (WSI) of Heilongjiang and Inner Mongolia has been increased by 138% and 129% due to grain export. Stress from water shortages is generally severe in export regions, and issues with the sustainability of grain production and VWF pattern are worthy of further exploration. PMID- 26851760 TI - Comparisons of soil nitrogen mass balances for an ombrotrophic bog and a minerotrophic fen in northern Minnesota. AB - We compared nitrogen (N) storage and flux in soils from an ombrotrophic bog with that of a minerotrophic fen to quantify the differences in N cycling between these two peatlands types in northern Minnesota (USA). Precipitation, atmospheric deposition, and bog and fen outflows were analyzed for nitrogen species. Upland and peatland soil samples were analyzed for N content, and for ambient (DN) and potential (DEA) denitrification rates. Annual atmospheric deposition was: 0.88 3.07kg NH4(+)ha(-1)y(-1); 1.37-1.42kg NO3(-)ha(-1)y(-1); 2.79-4.69kg TNha(-1)y( 1). Annual N outflows were: bog-0.01-0.04kg NH4(+)ha(-1)y(-1), NO3(-) 0.01 0.06kgha(-1)y(-1), and TN 0.11-0.69kgha(-1)y(-1); fen-NH4(+) 0.01-0.16kgha(-1)y( 1), NO3(-) 0.29-0.48kgha(-1)y(-1), and TN 1.14-1.61kgha(-1)y(-1). Soil N content depended on location within the bog or fen, and on soil depth. DN and DEA rates were low throughout the uplands and peatlands, and were correlated with atmospheric N deposition, soil N storage, and N outflow. DEA was significantly greater than DN indicating C or N limitation of the denitrification process. We highlight differences between the bog and fen, between the upland mineral soils and peat, and the importance of biogeochemical hotspots within the peatlands. We point out the importance of organic N storage, as a source of N for denitrification, and propose a plausible link between organic N storage, denitrification and N export from peatlands. Finally, we considered the interactions of microbial metabolism with nutrient availability and stoichiometry, and how N dynamics might be affected by climate change in peatland ecosystems. PMID- 26851761 TI - Reduction, methylation, and translocation of arsenic in Panax notoginseng grown under field conditions in arsenic-contaminated soils. AB - Variations in arsenic (As) species in Panax notoginseng grown under field conditions remain understudied compared with those under greenhouse conditions. In the present study, soil and plant samples were collected from Wenshan Zhuang and Miao Autonomous Prefecture, Yunnan Province, which is the main production area of P. notoginseng in China, to identify As species in the soil and plant tissues and further assess effect of As toxic stress on As transformation and translocation in P. notoginseng. The results showed that arsenate (As(V)) was almost exclusively identified in the soil, while arsenite (As(III)) and monomethylarsonic acid (MMA) were detected in high proportions in plant tissues, suggesting that As(V) could be reduced and subsequently methylated in the plant body, mainly in the root. The reduction and methylation of As in the root of P. notoginseng were promoted by low As toxic stress, but were impeded by high As toxic stress. Arsenic(III) and MMA could rapidly translocate upwards in P. notoginseng. In addition, the translocation of total As, As(III), and MMA from the root to the rhizome was a response to As toxic stress, and the translocation rate increased with the increasing As concentration in the taproot. This study provides new insights into the detoxification mechanism of P. notoginseng grown in As-contaminated soils and the control of As during cultivation. PMID- 26851762 TI - Persistent organic pollutants (POPs) in fish with different feeding habits inhabiting a shallow lake ecosystem. AB - The occurrence of persistent organic pollutants (POPs) in the environment can affect organisms inhabiting aquatic systems, in particular shallow lakes that are vulnerable to environmental stressors. This study aimed to assess POPs accumulation and changes at histological and physiological levels in tissues of three fish species with different trophic habits. Gills, brain, muscle, liver and gonads of Odontesthes bonariensis, Oligosarcus jenynsii and Cyphocharax voga were collected from the shallow lake La Peregrina, located in an agricultural area from Argentina. In addition, contaminant levels in surface water (SW), suspended particulate matter (SPM) and bottom sediments (BS) were assessed. Histological lesions were evaluated in fish tissues and levels of vitellogenin (VTG) were assessed in plasma of male fish in order to correlate these alterations with the presence of POPs in the environment. Organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) were determined by GC-ECD. Biotic and abiotic samples showed the same POPs distribution pattern: OCPs>PCBs>PBDEs. Although tissue distribution of OCPs was species-specific, muscle showed the lowest levels in all species. The most abundant contaminants were endosulfans, suggesting their widespread use in the area. O. bonariensis showed the highest endosulfans levels in liver (184.2 219ngg(-1)wet w), which was associated with the high SPM levels considering this species is a filter feeder. The occurrence of PCBs and PBDEs shows the ubiquity of these pollutants in the area. Histological lesions in gills and liver of O. bonariensis and O. jenynsii, might be related with the high levels of endosulfans in these organs. The detection of VTG in males warns about a possible exposure to estrogenic compounds in the environment. In conclusion, the simultaneous exposure of fish to multiple environmental pollutants leads to different alterations, so measures should be taken in order to prevent their occurrence and toxic effects. PMID- 26851763 TI - The multifunctional artificial reef and its role in the defence of the Mediterranean coast. AB - Multifunctional artificial reefs (MFAR) are being implemented around the world, due to their ability to provide an environment where a sports-economic recreational use and environmental improvement is implemented, and are also elements of coastal defence. However, a lot of failures have been recorded, possibly due to disregarded local factors in the formulations used, and there is no method that has encompassed all these factors, in order to take them into account in its design. The aim of this paper was to provide the coastal engineer with a method that would be used for the design of such reefs. To do this, the Babilonia beach of Guardamar del Segura, Alicante (Spain), was chosen because it is a fully anthropised area (with houses in the Maritime-Terrestrial Public Domain, marina, channelling and river mouth) with continuous regression, in which all the elements considered in this study, were treated. Based on the performance obtained in studies and projects worldwide, the climatic characteristics, biocenosis, sediment transport, settlements and liquefaction and the evolution of the coastline, were analysed. The multidisciplinary study carried out showed that with the implementation of a MFAR, the problem was reversed. Furthermore, the area was provided with a playful-economic use, and could be used 60% of the time, by surfers whose skill level were low to intermediate, without forgetting that the diversity of the marine ecosystem in the area was increased. PMID- 26851764 TI - Public reporting of assisted reproductive technology cycle outcomes is not simple. PMID- 26851765 TI - Optimizing the culture environment and embryo manipulation to help maintain embryo developmental potential. AB - With increased use of comprehensive chromosome screening (CCS), the question remains as to why some practices do not experience the same high levels of clinical success after implementation of the approach. Indeed, the debate surrounding the efficacy and usefulness of blastocyst biopsy and CCS continues. Importantly, several variables impact the success of an assisted reproductive technology cycle. Transfer of a euploid embryo is but one factor in an intricate system that requires numerous steps to occur successfully. Certainly, the culture environment and the manipulations of the embryo during its time in the laboratory can impact its reproductive potential. Environmental stressors ranging from culture media to culture conditions and even culture platform can impact biochemical, metabolic, and epigenetic patterns that can affect the developing cell independent of chromosome number. Furthermore, accompanying procedures, such as biopsy and vitrification, are complex and, when performed improperly, can negatively impact embryo quality. These are areas that likely still carry room for improvement within the IVF laboratory. PMID- 26851766 TI - Assisted reproductive technology: moving forward--or just moving? PMID- 26851768 TI - Behavioral effects of transcranial pulsed current stimulation (tPCS): Speed accuracy tradeoff in attention switching task. AB - Transcranial pulsed current stimulation (tPCS) has been shown to increase inter hemispheric coherence of brain oscillatory activity, mainly in fronto-temporal regions, leading to enhancement of functional connectivity across neural networks. The question is whether tPCS can modulate behavior significantly. Our aim was to identify the effects of tPCS on paired associative learning task (PALT) and attention switching task (AST), and to further categorize physiological autonomic responses by heart rate variability and electrodermal activity measurements before and after task performance. Thirty healthy volunteers were randomized to receive a single session of sham or active 2mA tPCS stimulation with a random frequency between 1 and 5Hz. We show that active tPCS significantly improved response time in the AST compared to sham stimulation, so that subjects who received active tPCS significantly exhibit decreased switching cost between repeat and switch trials. No differences were found in response accuracy on AST and PALT. No significant changes were observed in physiological parameters. Based on our results, we suggest that tPCS has a more pronounced effect on tasks that require the increase of functional connectivity across pre existent neural circuitry, rather than on tasks that require the development of new learning circuits or the creation of new connections. PMID- 26851767 TI - Serum thyroglobulin as a biomarker of iodine deficiency in adult populations. AB - OBJECTIVE: To clarify which factors may influence the serum Tg level in an adult population and how this may affect Tg as a biomarker of iodine deficiency (ID). DESIGN AND METHODS: Two identical cross-sectional studies were performed before (C1a: 1997-98, n = 4649) and after (C2: 2004-05, n = 3570) the Danish mandatory iodine fortification (IF) of salt (2000). Additionally, a follow-up study of C1a was performed after IF (C1b: 2008-10, n = 2465). The studies took place in two regions with mild (Copenhagen) and moderate (Aalborg) ID before IF. Serum Tg was measured by immunoradiometric method and investigated as outcome variable in multivariate models. RESULTS: Multiple factors were associated with serum Tg. Some were directly related to iodine intake (cohort, urinary iodine concentration (UIC) level and region), and some were likely mediators of iodine intake effects on Tg (thyroid nodularity, thyroid size and autonomy with low TSH). Others were caused by Tg assay interference (Tg-Ab positivity), aggravation of ID (childbirths and smoking) or TSH stimulation of the thyroid. Estimated 24-h urinary iodine excretion was a more sensitive predictor of Tg than UIC. Iodine supplement users had low median Tg values compared with nonusers both before and after IF. CONCLUSIONS: Multiple factors should be taken into consideration when evaluating Tg as a marker of ID in adult populations, and the Tg results may depend on the assay used. Still, Tg is a sensitive marker of ID. We suggest including a reference population with known sufficient iodine intake when Tg is used to evaluate ID. PMID- 26851770 TI - Ingroup favoritism or the black sheep effect: Perceived intentions modulate subjective responses to aggressive interactions. AB - Social categorization plays an important role in provoking the victim's responses to aggressive interactions. Pioneering studies suggested that uncertainty in the perpetrator's hostile intention influences whether ingroup favoritism or the black sheep effect (ingroup strictness) will be manifested to a greater extent. However, when the hostile intention is ambiguous, subjective perception of the perpetrator's intention may still be quite different due to the inherent information gap between participants, and this discrepancy in perceived intentions may further modulate subjective responses to social aggression. In the present study, subjects played as responders of the Ultimatum Game, and received varied offers proposed by either ingroup or outgroup members. Electrophysiological results showed that, when proposers were perceived to be intentional, unfair offers from ingroups elicited significantly larger Feedback related Negativity (FRN) than those from outgroups, potentially providing neural evidence for the black sheep effect. The opposite FRN pattern was observed when proposers were perceived to be unintentional, which might suggest ingroup favoritism. Interestingly, despite contrary neural patterns, perceived intentions did not modulate behavioral response to aggressive interactions. Thus, converging results suggested that, when the perpetrator's hostile intention remained ambiguous, perceived intentions modulated the victim's electrophysiological response while not the rational behavioral response to aggressive interactions. PMID- 26851771 TI - Presynaptic facilitation of glycinergic mIPSC is reduced in mice lacking alpha3 glycine receptor subunits. AB - Glycinergic neurons provide an important mechanism to control excitation of motoneurons in the brainstem and a reduction or loss of glycinergic inhibition can be deleterious by leading to hyperexcitation such as in hyperekplexia or neurodegeneration and neuronal death as in amyotrophic lateral sclerosis (ALS). Second messenger systems that change cyclic AMP and lead to phosphorylation of the alpha3 subunit of the glycine receptor (GlyR alpha3) have been shown to be potent modulators of synaptic inhibition in the spinal cord and brain stem. In this study we analyzed the role of GlyR alpha3 in synaptic inhibition to the hypoglossal nucleus using Glra3 (the gene encoding the glycine receptor alpha3 subunit) knockout mice. We observed that baseline glycinergic synaptic transmission to nucleus of hypoglossal motoneurons is rather normal in Glra3 knockout mice. Interestingly, we found that the modulation of synaptic transmission by cAMP-mediated pathways appeared to be reduced in Glra3 knockout mice. In the second postnatal week the forskolin-induced increase of miniature inhibitory postsynaptic potential (mIPSC) frequency was significantly larger in control as compared to Glra3 knockout mice suggesting that presynaptic glycine release in the hypoglossal nucleus is partially depending on GlyR alpha3. PMID- 26851769 TI - Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia. AB - Approximately half of moderate to severely hypoxic-ischemic (HI) newborns do not respond to hypothermia, the only proven neuroprotective treatment. N acetylcysteine (NAC), an antioxidant and glutathione precursor, shows promise for neuroprotection in combination with hypothermia, mitigating post-HI neuroinflammation due to oxidative stress. As mechanisms of HI injury and cell death differ in males and females, sex differences must be considered in translational research of neuroprotection. We assessed the potential toxicity and efficacy of NAC in combination with hypothermia, in male and female neonatal rats after severe HI injury. NAC 50mg/kg/d administered 1h after initiation of hypothermia significantly decreased iNOS expression and caspase 3 activation in the injured hemisphere versus hypothermia alone. However, only females treated with hypothermia +NAC 50mg/kg showed improvement in short-term infarct volumes compared with saline treated animals. Hypothermia alone had no effect in this severe model. When NAC was continued for 6 weeks, significant improvement in long term neuromotor outcomes over hypothermia treatment alone was observed, controlling for sex. Antioxidants may provide insufficient neuroprotection after HI for neonatal males in the short term, while long-term therapy may benefit both sexes. PMID- 26851772 TI - A novel histochemical method for the visualization of thrombin activity in the nervous system. AB - Although thrombin has an important role in both central and peripheral nerve diseases, characterization of the anatomical distribution of its proteolytic activity has been limited by available methods. This study presents the development, challenges, validation and implementation of a novel histochemical method for visualization of thrombin activity in the nervous system. The method is based on the cleavage of the substrate, Boc-Asp(OBzl)-Pro-Arg-4MbetaNA by thrombin to liberate free 4-methoxy-2-naphthylamine (4MbetaNA). In the presence of 5-nitrosalicylaldehyde, free 4MbetaNA is captured, yielding an insoluble yellow fluorescent precipitate which marks the site of thrombin activity. The sensitivity of the method was determined in vitro using known concentrations of thrombin while the specificity was verified using a highly specific thrombin inhibitor. Using this method we determined the spatial distribution of thrombin activity in mouse brain following transient middle cerebral artery occlusion (tMCAo) and in mouse sciatic nerve following crush injury. Fluorescence microscopy revealed well-defined thrombin activity localized to the right ischemic hemisphere in cortical areas and in the striatum compared to negligible thrombin activity contralaterally. The histochemical localization of thrombin activity following tMCAo was in good correlation with the infarct areas per triphenyltetrazolium chloride staining and to thrombin activity measured biochemically in tissue punches (85 +/- 35 and 20 +/- 3 mU/ml, in the cortical and striatum areas respectively, compared to 7 +/- 2 and 13 +/- 2 mU/ml, in the corresponding contralateral areas; mean +/- SEM; p<0.05). In addition, 24 h following crush injury, focal areas of highly elevated thrombin activity were detected in teased sciatic fibers. This observation was supported by the biochemical assay and western blot technique. The histochemical method developed in this study can serve as an important tool for studying the role of thrombin in physiological and pathological conditions. PMID- 26851773 TI - Mesenchymal stem cell-derived exosomes from different sources selectively promote neuritic outgrowth. AB - Mesenchymal stem cells (MSCs) obtained from bone marrow (BM) have been shown to promote neuronal growth and survival. However, the comparative effects of MSCs of different sources, including menstrual MSCs (MenSCs), BM, umbilical cord and chorion stem cells on neurite outgrowth have not yet been explored. Moreover, the modulatory effects of MSCs may be mediated by paracrine mechanisms, i.e. by molecules contained in the MSC secretome that includes soluble factors and extracellular vesicles such as microvesicles and/or exosomes. The biogenesis of microvesicles, characterized by a vesicle diameter of 50 to 1000 nm, involves membrane shedding while exosomes, of 30 to 100 nm in diameter, originate in the multivesicular bodies within cells. Both vesicle types, which can be harvested from the conditioned media of cell cultures by differential centrifugation steps, regulate the function of target cells due to their molecular content of microRNA, mRNA, proteins and lipids. Here, we compared the effect of human menstrual MSCs (MenSCs) mediated by cell-cell contact, by their total secretome or by secretome derived extracellular vesicles on neuritic outgrowth in primary neuronal cultures. The contact of MenSCs with cortical neurons inhibited neurite outgrowth while their total secretome enhanced it. The extracellular vesicle fractions showed a distinctive effect: while the exosome-enriched fraction enhanced neurite outgrowth, the microvesicle-enriched fraction displayed an inhibitory effect. When we compared exosome fractions of different human MSC sources, MenSC exosomes showed superior effects on the growth of the longest neurite in cortical neurons and had a comparable effect to BM-SC exosomes on neurite outgrowth in dorsal root ganglia neurons. Thus, the growth-stimulating effects of exosomes derived from MenSCs as well as the opposing effects of both extracellular vesicle fractions provide important information regarding the potential use of MenSCs as therapeutic conveyors in neurodegenerative pathologies. PMID- 26851775 TI - Glycine-rich conotoxins from the Virgiconus clade. AB - Cone snails in the Virgiconus clade prey on marine worms. Here, we identify six related conotoxins in the O1-superfamily from three species in this clade, Conus virgo, Conus terebra and Conus kintoki. One of these peptides, vi6a, was directly purified from the venom of C. virgo by following its activity using calcium imaging of dissociated mouse dorsal root ganglion (DRG) neurons. The purified peptide was biochemically characterized, synthesized and tested for activity in mice. Hyperactivity was observed upon both intraperitoneal and intracranial injection of the peptide. The effect of the synthetic peptide on DRG neurons was identical to that of the native peptide. Using the vi6a sequence, five other homologs were identified. These peptides define a glycine-rich subgroup of the O1 superfamily from the Virgiconus clade, with biological activity in mice. PMID- 26851776 TI - Interaction between antimicrobial peptides and mycobacteria. AB - Mycobacteria can cause different severe health problems, including tuberculosis (TB). The treatment of TB with conventional antibiotics is successful, however, the number of multi-drug and extensively-drug resistant Mycobacterium tuberculosis strains increases. Moreover, many classical antimycobacterial antibiotics have severe side effects. Therefore, antimicrobial peptides (AMPs) seem to be good candidates for new therapeutic strategies. On the one hand AMPs can be used as a single drug or in combination with conventional antibiotics to directly kill mycobacteria, or on the other hand to act as immunstimulatory agents. This review summarizes the findings on the role of endogenous human AMPs being involved in TB, the antimycobacterial activity of various AMPs, and the molecular modes of action. Most active AMPs interact with the mycobacterial cell envelope and in particular with the mycomembrane and the plasma membrane. The mycomembrane is a very rigid membrane probably leading to a lower activity of the AMPs against mycobacteria as compared to other Gram-negative or Gram-positive bacteria. For some AMPs also other targets have been identified. Because of the complex environment of intracellular mycobacteria being trapped in the phagosome, within the macrophage, within the granuloma, within the lung, the external administration of AMPs in the latent phase of TB is a challenge. However, in the acute phase the AMPs can attack mycobacteria in a direct way. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert. PMID- 26851774 TI - Neurophysiology of rule switching in the corticostriatal circuit. AB - The ability to adjust behavioral responses to cues in a changing environment is crucial for survival. Activity in the medial Prefrontal Cortex (mPFC) is thought to both represent rules to guide behavior as well as detect and resolve conflicts between rules in changing contingencies. While lesion and pharmacological studies have supported a crucial role for mPFC in this type of set-shifting, an understanding of how mPFC represents current rules or detects and resolves conflict between different rules is still unclear. Meanwhile, medial dorsal striatum (mDS) receives major projections from mPFC and neural activity of mDS is closely linked to action selection, making the mDS a potential major player for enacting rule-guided action policies. However, exactly what is signaled by mPFC and how this impacts neural signals in mDS is not well known. In this review, we will summarize what is known about neural signals of rules and set shifting in both prefrontal cortex and dorsal striatum, as well as provide questions and directions for future experiments. PMID- 26851778 TI - Evaluation of antiviral activities of Houttuynia cordata Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection. AB - OBJECTIVE: To evaluate the in vitro activities of the ethyl acetate (EA) fraction of Houttuynia cordata (H. cordata) Thunb. (Saururaceae) and three of its constituent flavonoids (quercetin, quercitrin and rutin) against murine coronavirus and dengue virus (DENV). METHODS: The antiviral activities of various concentrations of the EA fraction of H. cordata and flavonoids were assessed using virus neutralization tests against mouse hepatitis virus (MHV) and DENV type 2 (DENV-2). Cinanserin hydrochloride was also tested against MHV. The EA fraction of H. cordata was tested for acute oral toxicity in C57BL/6 mice. RESULTS: The EA fraction of H. cordata inhibited viral infectivity up to 6 d. Cinanserin hydrochloride was able to inhibit MHV for only 2 d. The 50% inhibitory concentrations (IC50) of the EA fraction of H. cordata added before the viral adsorption stage were 0.98 MUg/mL for MHV and 7.50 MUg/mL for DENV-2 with absence of cytotoxicity. The mice fed with the EA fraction up to 2000 mg/kg did not induce any signs of acute toxicity, with normal histological features of major organs. Certain flavonoids exhibited comparatively weaker antiviral activity, notably quercetin which could inhibit both MHV and DENV-2. This was followed by quercitrin which could inhibit DENV-2 but not MHV, whereas rutin did not exert any inhibitory effect on either virus. When quercetin was combined with quercitrin, enhancement of anti-DENV-2 activity and reduced cytotoxicity were observed. However, the synergistic efficacy of the flavonoid combination was still less than that of the EA fraction. CONCLUSIONS: The compounds in H. cordata contribute to the superior antiviral efficacy of the EA fraction which lacked cytotoxicity in vitro and acute toxicity in vivo. H. cordata has much potential for the development of antiviral agents against coronavirus and dengue infections. PMID- 26851777 TI - Synaptobrevin transmembrane domain determines the structure and dynamics of the SNARE motif and the linker region. AB - The vesicular protein synaptobrevin II (sybII) constitutes a central component of the SNARE complex, which mediates vesicle fusion in neuronal exocytosis. Previous studies revealed that the transmembrane domain (TMD) of sybII is playing a critical role in the fusion process and is involved in all distinct fusion stages from priming to fusion pore opening. Here, we analyzed sequence-dependent effects of sybII and of mutants of sybII on both structure and flexibility of the protein and the interactions with a phospholipid bilayer by means of microsecond atomistic simulations. The sybII TMD was found to direct the folding of both the juxtamembrane helix and of the connecting linker and thus to influence both the intrinsic helicity and flexibility. Fusion active peptides revealed two helical segments, one for the juxtamembrane region and one for the TMD, connected by a flexible linker. In contrast, a fusion-inactive poly-leucine TMD mutant assumes a structure with a comparably rigid linker that is suggested to hinder the formation of the trans-SNARE complex during fusion. Kinking of the TMD at the central glycine together with anchoring of the TMD via conserved tryptophans and a lysine in position 94 likely yields an enhanced flexibility of sybII for different membrane thickness. All studied peptides were found to deform the outer membrane layer by altering the lipid head group orientation, causing partial membrane dehydration and enhancing lipid protrusions. These effects weaken the integrity of the outer membrane layer and are attributed mainly to the highly charged linker and JM regions of sybII. PMID- 26851779 TI - Non-aqueous extracts of Curcuma mangga rhizomes induced cell death in human colorectal adenocarcinoma cell line (HT29) via induction of apoptosis and cell cycle arrest at G0/G1 phase. AB - OBJECTIVE: To investigate the cytotoxic activity of the hexane and ethyl acetate extracts of Curcuma mangga rhizomes against human colorectal adenocarcinoma cell lines (HT29). METHODS: The cytotoxic activity of the hexane and ethyl acetate extracts of Curcuma mangga rhizomes against human colorectal adenocarcinoma cell lines (HT29) was determined by using the SRB assay. RESULTS: The ethyl acetate extract showed a higher cytotoxic effect compared to the hexane extract. Morphological changes of the HT29 cells such as cell shrinkage, membrane blebbling and formation of apoptotic bodies while changes in nuclear morphology like chromatin condensation and nuclear fragmentation were observed. Further evidence of apoptosis in HT29 cells was further supported by the externalization of phosphatidylserine which indicate early sign of apoptosis. CONCLUSIONS: The early sign of apoptosis is consistent with the cell cycle arrest at the G0/G1 checkpoint which suggests that the changes on the cell cycle lead to the induction of apoptosis in HT29. PMID- 26851780 TI - Potentiating activity of luteolin on membrane permeabilizing agent and ATPase inhibitor against methicillin-resistant Staphylococcus aureus. AB - OBJECTIVE: To investigate the mechanism of antibacterial activity of luteolin (LUT) against methicillin-resistant Staphylococcus aureus (MRSA). METHODS: The mechanism of anti-MRSA activity of LUT was analyzed by the viability assay in membrane permeabilizing agent, ATPase inhibitors, and peptidoglycan (PGN) derived from Staphylococcus aureus (S. aureus). Also, transmission electron microscopy was used to monitor survival characteristics and changes in S. aureus morphology. RESULTS: Compared to the LUT alone, the optical density of suspensions treated with the combination of 125 MUg/mL Tris and 250 MUg/mL N,N' dicyclohexylcarbodiimide were reduced to 60% and 46% of the control, respectively. PGN (15.6 MUg/mL) gradually impeded the activity of LUT, and PGN (62.5 MUg/mL) completely blocked the activity of LUT on S. aureus. CONCLUSIONS: Increased susceptibility to LUT with the Tris-dicyclohexylcarbodiimide combinations is evident in all tested MRSA isolates. The results indicate LUT synergy in increasing cytoplasmic membrane permeability and inhibiting ATPase. S. aureus PGN directly blocks the antibacterial activity of LUT, suggesting the direct binding of LUT with PGN. These findings may be validated for the development of antibacterial agent for low MRSA resistance. PMID- 26851781 TI - Evaluation of activity of triclabendazole against Taenia solium metacestode in naturally infected pigs. AB - OBJECTIVE: To assess the efficacy of triclabendazole (TCBZ) in porcine cysticercosis. METHODS: Eighteen naturally infected cysticercosis pigs were divided into 3 groups of 6 individuals each. The first group was treated orally with TCBZ at a single dose of 30 mg/kg of body weight, the second group was treated orally with oxfendazole at a single dose of 30 mg/kg of body weight and the third group received a placebo (control group). All animals were kept under the same management conditions. The pigs were euthanized 17 wk post-treatment and the number of surviving cysts in muscles was assessed and compared between groups. RESULTS: All pigs treated with oxfendazole had only degenerated cysts in their carcasses. In contrast, TCBZ had very little effect against the parasitic cysts. Cysts from pigs in the TCBZ group looked apparently normal after treatment. However, histological evaluation showed a mild to moderate degree of inflammation. CONCLUSIONS: TCBZ is not an efficacious drug against Taenia solium cysticercosis in swine using a single dose. PMID- 26851782 TI - Enterobacteria and Vibrio from Macrobrachium amazonicum prawn farming in Fortaleza, Ceara, Brazil. AB - OBJECTIVE: To investigate the isolation of enterobacteria associated with Macrobrachium amazonicum (M. amazonicum) farming and evaluate the in vitro antimicrobial susceptibility of Vibrio strains. METHODS: Strains were isolated from female M. amazonicum prawns and environmental and hatchery water. Biochemical assays were used to identify bacterial genera and those belonging to the genus Vibrio were submitted to further analyses for species identification, through Vitek 2 automated system and serotyping. Susceptibility test was performed according to Clinical Laboratory Standards Institute. RESULTS: The following genera of enterobacteria were recovered: Enterobacter (n = 11), Citrobacter (n = 10), Proteus (n = 2), Serratia (n = 2), Kluyvera (n = 2), Providencia (n = 2), Cedecea (n = 1), Escherichia (n = 1), Edwardsiella (n = 1) and Buttiauxella (n = 1). As for Vibrio, three species were identified: Vibrio cholerae non-O1/non-O139 (n = 4), Vibrio vulnificus (V. vulnificus) (n = 1) and Vibrio mimicus (n = 1). Vibrio spp. showed minimum inhibitory concentrations values within the susceptibility range established by Clinical Laboratory Standards Institute for almost all antibiotics, except for V. vulnificus, which presented intermediate profile to ampicillin. CONCLUSIONS: Enterobacteria do not seem to be the most important pathogens associated with M. amazonicum farming, whereas the recovery of Vibrio spp. from larviculture, with emphasis on Vibrio cholerae and V. vulnificus, deserves special attention due to their role as potentially zoonotic aquaculture-associated pathogens. Furthermore, the intermediate susceptibility of V. vulnificus to ampicillin reflects the importance of monitoring drug use in prawn farming. PMID- 26851783 TI - Bio-ecology of malaria vectors in an endemic area, Southeast of Iran. AB - OBJECTIVE: To determine some bio-ecological aspects of malaria vectors in Jask County, where is targeted for malaria elimination in the national program. METHODS: Mosquitoes were collected monthly during 2013-2014 using different collection methods. Subsequently, ELISA test was used to detect the human blood index of mosquitoes. The susceptibility status of Anopheles stephensi was evaluated against the diagnostic dosages of seven WHO recommended insecticides. RESULTS: A total of 3650 female and 4736 Anopheles larvae were collected including Anopheles stephensi, Anopheles culicifacies s.l., Anopheles dthali, Anopheles fluviatilis s.l., Anopheles moghulensis and Anopheles turkhodi species. Anopheles stephensi was the dominant collected species on human baits and indoors with high rate of unfed and gravid specimens in internal and external window traps. Human blood index was calculated as 14.3% for this species. It was also found to be resistant to DDT and Dieldrin. CONCLUSIONS: The collected species had a wide range of habitats, and resting behaviors. With regarding to the presence of most important malaria vectors in Jask, control of the disease may be so complicated; as based on the weather condition it can be transmitted during the whole year, expect for cold months. With this strong potential of transmission, existing population movements in the area may lead to imported cases of malaria and local outbreak(s). So, more specific studies on malaria vectors in high risk areas of Jask County are recommended. PMID- 26851784 TI - Surveillance of dengue and chikungunya infection in Dong Thap, Vietnam: A 13 month study. AB - OBJECTIVE: To establish a surveillance in Dong Thap, at the border with Cambodia by assessing the presence of DENV serotypes and CHIKV among patients hospitalized at Dong Thap general hospital. METHODS: Cross-sectional descriptive analysis was conducted on a cohort of 131 patients hospitalized with acute fever and symptoms compatible with dengue or chikungunya. The study was conducted from January 2012 to February 2013. The full clinical picture was established as well as serological and molecular detection. Serological analysis was sequentially performed on blood samples collected on admission and an average of seven days after admission. The detection of IgM antibody to DENV was performed by IgM capture ELISA and the detection of DENV and CHIKV RNA was done by reverse transcription multiplex PCR. RESULTS: 101 patients out of 131 (77%) were confirmed with dengue. All four dengue serotypes were detected with a predominance of DENV2 and DENV4. No chikungunya infection was detected although reported in neighboring Cambodia. A differential efficiency of serological dengue detection was observed. Efficiency was 29% upon admission and 53% after seven days on the same patients. 30 patients out of 131 (23%) were negative with both DENV and CHIKV. CONCLUSIONS: Dengue is at risk of being underestimated and chikungunya is not systematically detected. Changes in detection and surveillance procedures are therefore discussed to increase efficiency of dengue detection and continue the monitoring the emergence of CHIKV in Dong Thap province and in Vietnam. PMID- 26851785 TI - Prevalence of intestinal parasite infections among patients in local public hospitals of Hail, Northwestern Saudi Arabia. AB - OBJECTIVE: To evaluate the prevalence of intestinal parasites among patients in Hail, Northwestern Saudi Arabia. METHODS: Stool samples were collected from 130 patients (69 females and 61 males) in Hail General Hospital. Each sample was examined by direct wet mount microscopic examination using both normal saline and Lugol's iodine preparation and concentration techniques using salt and formol ether solutions. Permanent stained smears were performed for intestinal coccidian using modified Ziehl-Neelsen technique. RESULTS: The overall prevalence of intestinal parasitic infection was 45.38% (59 cases). Forty-four (33.84%) were found to be infected with one or more intestinal protozoa, 5 (3.84%) were infected with helminthes and 10 (7.69%) had mixed infection with both helminthes and protozoa. The most common intestinal helminth detected was Ancylostoma duodenale (n = 5, 3.84%), followed by Ascaris lumbricoides, Taenia sp. and Trichuris trichiura (n = 2 for each species, 1.5%). For intestinal protozoa, the coccidian Cryptosporidium parvum (n = 25, 19.23%) was the most common followed by Entamoeba histolytica/dispar (n = 21, 16.15%), Giardia lamblia (n = 15, 11.54%), Entamoeba coli (n = 5, 3.85%) and Blastocystis hominis (n = 3, 2.30%). The prevalence of intestinal parasitic infections in females was significantly higher than in males (P < 0.05). CONCLUSIONS: This is the first study highlighting that intestinal parasites are still an important public health problem in Northwestern Saudi Arabia. Therefore, health education would be the best way to prevent from intestinal parasite infections which are mainly food borne diseases. PMID- 26851786 TI - MEK/ERK signaling pathway in apoptosis of SW620 cell line and inhibition effect of resveratrol. AB - OBJECTIVE: To study the involvement of MAPK MEK/ERK signaling transduction pathway in the apoptosis process of SW620 tumor cell line and the inhibition effect of resveratrol. METHODS: SW620 cell lines were divided into 5 groups, namely, control group, PD98059 group, low-dose resveratrol group, mid-dose resveratrol group and high-dose resveratrol group. The inhibition rate of cell proliferation was detected by MTT method. The expression of apoptotic molecules and MEK/ERK signaling pathway related proteins were assayed by real-time PCR and Western blotting. RESULTS: Compared with control group, the proliferation of cells treated with resveratrol was significantly inhibited. In the case of apoptotic molecules, the expression of Bax, Caspase 3 and Caspase 9 was increased significantly while the expression of anti-apoptotic molecule Bcl2 was decreased significantly in resveratrol groups with a dose-dependent manner. In the case of molecules in MEK/ERK signaling pathway, the expression of Ras, Raf, MEK and ERK1/2 was decreased significantly in resveratrol groups with a dose-dependent manner. CONCLUSIONS: PD98059 and resveratrol can effectively inhibit the proliferation of SW620 through inhibiting the MEK/ERK signaling pathway. PMID- 26851787 TI - Effect of vitamin D3 on maturation and antigen-presenting function of dendritic cells treated with Mycobacterium tuberculosis. AB - OBJECTIVE: To investigate the phenotypic characteristics and functional capability differences of mouse bone marrow-derived dendritic cells after stimulation with Mycobacterium tuberculosis in the presence or absence of vitamin D3. METHODS: Mouse bone marrow-derived cells were cultured with GM-CSF (20 ng/mL). Then, one was added with 100 nmol/L of 25(OH)D3, while the other did not. On day 6, 5 MUg/mL of BCG was added to stimulate the cells for 24 h. On day 7, suspension cells were harvested for phenotypic and functional analyses. RESULTS: The percentages of CD86 dendritic cells (DCs) in the control group and 25(OH)D3 group were 66.97% +/- 8.29% and 52.18% +/- 8.52%, respectively; the mean fluorescence intensities of MHC-II in the control group and 25(OH)D3 group were 1 102.16 +/- 371.02 and 681.62 +/- 292.71. The expression levels of MHC- II and CD86 on the surface of the DCs in 25(OH)D3 group were significantly lower than those of the control group. The ability of the DCs to stimulate proliferation of T-lymphocytes was also significantly lower than that of the control group. CONCLUSIONS: These findings suggest that 25(OH)D3 modulates the immune response by affecting the maturation and function of DCs in Mycobacterium tuberculosis period. PMID- 26851788 TI - Mechanism of Wnt/beta-catenin signaling pathway in enhanced malignant phenotype of non-small cell lung cancer induced by anti-angiogenesis therapy. AB - OBJECTIVE: To study the mechanism of Wnt/beta-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the anti-angiogenesis therapy. METHODS: The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor (VEGF) in A549 cells and simulate the clinical course of anti-angiogenesis therapy. Real time PCR and western blot were used to study the change in the expression of Wnt/beta-catenin signaling molecules at the mRNA and protein level respectively, as well as the effect on the epithelial mesenchymal transition in A549 cells. The proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/beta-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis therapy. RESULTS: The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis therapy. Under the action of 50 nM VEGF siRNA, the proliferation ability of A549 significantly increased (P < 0.05). After being treated with VEGF siRNA, the invasion ability of cells increased. Twenty-four hours after the transcription of 50 nM siRNA into cells, the number of cells that come through the membrane was 278.3 +/- 12.9. Compared with the Ctrl siRNA group, when VEGF was inhibited, the expression of beta-catenin and Cyclin D1 increased by 86% and 55% respectively. Meanwhile, the expression of E cadherin decreased, while the one of vimentin increased. CONCLUSIONS: siRNA can significantly inhibit the expression of VEGF. For the anti-angiogenesis therapy, the inhibited expression of VEGF can activate the Wnt/beta-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer. PMID- 26851789 TI - Influence of Toxoplasma gondii on in vitro proliferation and apoptosis of hepatoma carcinoma H7402 cell. AB - OBJECTIVE: To discuss the influence of tachyzoite of Toxoplasma gondii (T. gondii) RH strain on proliferation and apoptosis of hepatoma carcinoma (HCC) H7402 cell. METHODS: The HCC H7402 cell in logarithmic phase and tachyzoite of T. gondii RH strain in different concentrations (1 * 10(7)/mL, 2 * 10(7)/mL, 4 * 10(7)/mL, 8 * 10(7)/mL and 16 * 10(7)/mL) were co-cultured. CCK-8 was utilized to determine the inhibition rate of T. gondii tachyzoite on H7402 cell growth. Flow cytometry was used to detect the change of cell cycle. RT-PCR method was used to detect the expression of cyclinB1 and cdc2-two genes related to cell cycle. Western blot method was used to detect the expression of apoptosis-related proteins Caspase-3 and Bcl-2. RESULTS: The tachyzoite of T. gondii RH strain can inhibit the proliferation of HCC H7402 cells. The inhibition rate of tumor cell growth increased with the increase of concentration of T. gondii tachyzoite. With the increase of concentration of T. gondii tachyzoite, the proportion of G0/G1 phase of H7402 cell increased, the proportion of S phase decreased, and PI value decreased accordingly. The expression of cyclinB1 and cdc2 genes decreased with the increase of the concentration of T. gondii tachyzoite. With the increase of the concentration of tachyzoite of T. gondii RH strain, the expression quantity of Caspase-3 in H7402 cell increased, but the expression quantity of Bcl-2 protein decreased. CONCLUSIONS: T. gondii can inhibit the in vitro proliferation of HCC H7402 cell, and induce its apoptosis. This effect shows a trend of concentration-dependent increase. Moreover, it is related to the down-regulation of cyclinB1 and cdc2 (cell cycle-related genes), the increase of apoptosis related protein Caspase-3, and the decrease of Bcl-2 expression. PMID- 26851790 TI - Expression of TRAP1 in gastric cancer tissue and its correlation with malignant biology. AB - OBJECTIVE: To study the expression of tumor necrosis factor receptor-associated protein 1 (TRAP1) in gastric cancer tissue and its correlation with malignant biology. METHODS: Gastric cancer tissue and adjacent normal tissue were collected, and mRNA content and protein content of TRAP1 were detected; gastric cancer cell lines SGC7901, BGC823, AGS and MGC803 were cultured, and mRNA contents and protein contents of TRAP1, CyclinB1, CyclinD1, CyclinE, MMP-2 and VEGF were detected. RESULTS: mRNA and protein expression levels of TRAP1 in gastric cancer tissue were significantly higher than those in adjacent normal tissue, and mRNA and protein expression levels of TRAP1 in gastric cancer tissue with muscularis and serosa infiltration, lymph node metastasis, distant organ metastasis and TNM III/IV stage were significantly higher than those in gastric cancer tissue with mucosa and submucosa infiltration, non-lymph node metastasis, non-distant organ metastasis and TNM I/II stage. mRNA and protein expression levels of TRAP1, CyclinB1, CyclinD1, CyclinE, MMP-2 and VEGF in MGC803 were the highest, and mRNA and protein expression levels of TRAP1, CyclinB1, CyclinD1, CyclinE, MMP-2 and VEGF in SGC7901 were the lowest. mRNA and protein expression levels of TRAP1 in gastric cancer cell lines were positively correlated with mRNA and protein expression of CyclinB1, CyclinD1, CyclinE, MMP-2 and VEGF. CONCLUSIONS: The expression of TRAP1 significantly increases in gastric cancer tissue; TRAP1 may regulate the malignant biology of cells by increasing the expression of CyclinB1, CyclinD1, CyclinE, MMP-2 and VEGF, thereby resulting in the occurrence and development of gastric cancer. PMID- 26851791 TI - Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3. AB - OBJECTIVE: To explore the expression of microRNA (miRNA) let-7c and its function in chronic obstructive pulmonary disease (COPD) and alveolar macrophage cells. METHODS: Real time PCR was performed to detect the expression of miRNA let-7c in the lung tissue of COPD patients and COPD model in mice. MiRNA let-7c was overexpressed in alveolar macrophages isolated from mice and its effect was measured by the production of pro-inflammation cytokines and the protein level of signal transducer and activator of transcription 3 (STAT3) as well as phosphorylation level of STAT3 after LPS stimulation. Luciferase assay was used to detect the binding of miRNA let-7c and 3'UTR of STAT3. RESULTS: MiRNA let-7c expression was significantly lower in patients with COPD compared with control group, and the similar result was found in COPD mice and LPS stimulated alveolar macrophages. Overexpression of miRNA let-7c in alveolar macrophages inhibited LPS induced increasing of tumor necrosis factor alpha, interleukin-6 and interleukin 1beta. Luciferase assay showed STAT3 was a targeting of miRNA let-7c in alveolar macrophages. CONCLUSIONS: MiRNA let-7c low expression in COPD can regulate inflammatory responses by targeting STAT3 in alveolar macrophage, which may provide a new target for COPD treatment strategies. PMID- 26851792 TI - Protective effect of hyperoside on cardiac ischemia reperfusion injury through inhibition of ER stress and activation of Nrf2 signaling. AB - OBJECT: To study the protective effect of hyperoside (Hyp) on cardiac ischemia reperfusion injury and its potential mechanism. METHODS: Rats were divided into two groups for the evaluation, the Hyp (50 MUM Hyp; n = 8) and the control group (n = 8). Rat hearts were isolated and perfused with Krebs-Henseleit buffer (KHB) for 30 min. After being inhibited with cardioplegic solution, they were stored for 4 h in B21 solution at 4 degrees C. Afterwards, rat hearts were perfused with KHB again for 45 min. In this period, Hyp was added into solutions of cardioplegia for storage and KHB. Parameters of cardiac functions, including heart rate, the systolic pressure of the left ventricle, the end-diastolic pressure of the left ventricle, the developed pressure of the left ventricle, the left-ventricular systolic pressure and the peak rise rate of the pressure of the left ventricle were recorded. The levels of adenosine triphosphate (ATP), the content of malondialdehyde and apoptotic cells were determined to evaluate the protective effect of Hyp on hearts suffered from ischemia reperfusion injury. Moreover, cultured cardiac myocytes were subjected to the process simulating ischemia/reperfusion. What were analyzed included the endoplasmic reticulum (ER) stress hallmarks expressions, such as binding immunoglobulin protein and C/EBP homologous protein, using the western blot and real-time PCR. Besides, the NF-E2 related factor 2 (Nrf2) expression was measured to explore the potential mechanism. RESULTS: Compared with the control group, the Hyp group had better cardiac functional parameters and higher ATP levels; pretreatment of Hyp greatly relieved the apoptosis of myocyte, decreased oxidative stress as well as ER stress and activated the signaling pathway of anti-oxidative Nrf2 to a further extent. CONCLUSIONS: Hyp plays an important role in preserving cardiac function by improving ATP levels of tissue, easing oxidative injury of myocardium and reducing apoptosis following IRI dramatically, while the ER stress inhibition and the downstream Nrf2 signaling activation may contribute to the effects of protection. PMID- 26851793 TI - Therapeutic and recurrence-preventing effects of Qi-Replenishing and Blood Activating Formula in rats with acetic acid-induced gastric ulcer. AB - OBJECTIVE: To explore the therapeutic and recurrence-preventing effects of Qi Replenishing and Blood-Activating Formula in rats with acetic acid-induced gastric ulcer. METHODS: A total of 138 SD rats were selected to make rat models with gastric ulcer induced by acetic acid (24 rats with sham operation served as sham operation group), and were randomly divided into model group (n = 30), western medicine group (n = 30), traditional Chinese medicine (TCM) group (n = 24) and combination group (combined western medicine and TCM group, n = 30). Western medicine group was gavaged with omeprazole in the morning and with iso volumetric distilled water in the afternoon; TCM group and TCM sham operation group were gavaged with iso-volumetric distilled water in the morning and with Qi Replenishing and Blood-Activating Formula in the afternoon; combination group was gavaged with omeprazole in the morning and with Qi-Replenishing and Blood Activating Formula in the afternoon; sham operation group and model group were gavaged with iso-volumetric distilled water both in the morning and afternoon. Ulcer indexes and degree of mucosal degree in rats at different time points after gavage were observed. Twenty-eight days after gavage, interleukin (IL)-1beta was given to induce ulcer recurrence so as to observe the recurrent severity and rate of ulcer in each group. RESULTS: Compared with model group and western medicine group, treatment in combination group could prominently reduce the ulcer index of rats with peptic ulcer, and increase the healing rate and inhibition rate of peptic ulcer. After IL-1beta-induced ulcer recurrence, combination group was significantly superior to model group and western medicine group in ulcer recurrent rate [50% (3/6) vs. 100% (6/6)] and severity. CONCLUSIONS: Basic acid suppression therapy combined with Qi-Replenishing and Blood-Activating Formula can effectually improve the ulcer healing quality and reduce ulcer recurrence. PMID- 26851794 TI - Effect of recombinant human endostatin onradiotherapy for esophagus cancer. AB - OBJECTIVE: To investigate the effect of radiotherapy plus recombinant human endostatin (RH-endostatin) on esophageal cancer and its mechanism. METHODS: A total of 50 nudemice were equally randomized into control group, radiotherapy group, and combined therapy group I, II, and III after inoculating with Eca109 cell suspension (1 * 10(7) cells/mL). On the day of grouping, control group and radiotherapy group were injected normal saline, while radiotherapy group and 3 combined therapy groups received radiotherapy; besides, combined therapy group I, II, and III was injected RH-endostatin of 2.5, 5, 10 mg/kg respectively. After 3 week therapy, the tumors of each group were collected and microvessel density and VEGF expression in tumors were determined. In vitro, Eca109 cells were divided into control group, radiotherapy group, and combined therapy group. Forty-eight hours after treatment, cell cycle distribution and apoptosis rate were detected, and the activity of VEGF signal paths was semiquantitatively analyzed. RESULTS: Since the 6th day of treatment, the relative tumor proliferation rate of combined therapy group II was lower than radiotherapy group (P < 0.05) and <=40% since the 15th day. Average microvessel density and EGFR expression in combined therapy group II were lower than radiotherapy group (P < 0.05). In vitro, the cell percentage in S and G2/M phase of combined therapy group cells was lower than that in radiotherapy group cells, while the apoptosis rate and the expression of VEGF, AKT, p-AKT, ERK1/2 and p-ERK1/2 in combined group were higher than that in radiotherapy group (P < 0.05). CONCLUSIONS: RH-endostatin promotes the efficacy of radiotherapy on esophageal cancer, which may be partly realized by inhibiting the activity of VEGF related signal paths. PMID- 26851795 TI - Effect of insulin and metformin on methylation and glycolipid metabolism of peroxisome proliferator-activated receptor gamma coactivator-1A of rat offspring with gestational diabetes mellitus. AB - OBJECTIVE: To discuss the effect of insulin and metformin on a methylation and glycolipid metabolism of peroxisome proliferator-activated receptor gamma coactivator-1A (PPARGC1A) of rat offspring with gestational diabetes mellitus (GDM). METHODS: A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM. A total of 21 pregnant rats with GDM were randomly divided into three groups, with 7 rats in each group, namely the insulin group, metformin group and control group. Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day. Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day, with the first dose of 300 mg/kg. The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L. Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day. After the natural delivery of pregnant rats, 10 offspring rats were randomly selected from each group. At birth, 4 wk and 8 wk after the birth of offspring rats, the weight of offspring rats was measured. The blood glucose level of offspring rats was measured at 4 wk and 8 wk, while the level of serum insulin, triglyceride and leptin was measured at 8 wk. RESULTS: The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group (P < 0.05), and there was no significant difference at 4 wk and 8 wk among three groups (P > 0.05). The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group (P < 0.05); there was no significant difference between the insulin group and metformin group (P > 0.05). The expression of PPARGC1A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1A was significantly lower than the one in the control group (P < 0.05); but there was no significant difference between the insulin group and metformin group (P > 0.05). Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher, while triglyceride was significantly lower than the one in the control group (P < 0.05); triglyceride level in the insulin group was significantly higher than the one in the metformin group (P < 0.05). There was no significant difference in insulin and leptin level between the insulin group and metformin group (P > 0.05). CONCLUSIONS: GDM can induce the methylation of PPARGC1A of offspring rats to reduce the expression of PPARGC1A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up; the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1A and thus improve the abnormal glycolipid metabolism of offspring rats. PMID- 26851796 TI - Effects of Ang II perfusion on transmural heterogeneous of Cx43 in acute myocardial ischemia reperfusion. AB - OBJECTIVE: To observe the effects of angiotensin II(Ang II) perfusion on transmural heterogeneity of Cx43 expression in the rabbit model with acute myocardial ischemia reperfusion (MIR), and investigate the role of rennin angiotensin system in malignant ventricular arrhythmia induced by MIR. METHODS: Twenty rabbits were randomly divided into MIR group (n = 10) and Ang II group (n = 10). MIR model was produced with traditional ligation and opening of the anterior descending coronary artery in all animal. The hearts in vitro in the MIR group and the Ang II group were perfused with simply improved Tyrode's solution and containing Ang II Tyrode's solution respectively. 90% monophasic action potential repolarization duration, transmural dispersion of repolarization, Cx43 protein (Cx43-pro) and mRNA (Cx43-Cq) expression in subepicardial, midmyocardial and subendocardial myocardium were measured in both groups. The greatest differences of Cx43-pro and Cx43-Cq among three myocardial layers were calculated and shown with DeltaCx43-pro and DeltaCx43-Cq respectively. RESULTS: After Ang II perfusion, 90% monophasic action potential repolarization duration among three myocardial layer were significantly prolonged (P < 0.05 and P < 0.01), and transmural dispersion of repolarization also significantly increased compared with the MIR group (P < 0.05). Compare with the MIR group, three myocardial Cx43 pro and Cx43-Cq expression in the Ang II group were significantly decreased (P < 0.05 and P < 0.01), but DeltaCx43-pro and DeltaCx43-Cq were significant increased. CONCLUSIONS: Renin-angiotensin system increases transmural heterogeneity of Cx43 expression in the rabbit model with MIR by Ang II, and enlarge transmural dispersion of repolarization among three myocardial layers of left ventricular which induces malignant ventricular arrhythmia. PMID- 26851797 TI - Neurocysticercosis: A case report and brief review. AB - Neurocysticercosis (NCC) is one of the seven neglected endemic zoonoses targeted by the World Health Organization. It is considered a common infection of the nervous system caused by the Taenia solium and is known to be the primary cause of preventable epilepsy in many developing countries. NCC is commonly resulted by the ingestion of Taenia solium eggs after consuming undercooked pork, or contaminated water. The parasite can grow in the brain and spinal cord within the nervous system, causing severe headache and seizures beside other pathological manifestations. Immigration and international travel to endemic countries has made this disease common in the United States. NCC can be diagnosed with computed tomography and magnetic resonance imaging of the brain. The treatment of the NCC including cysticidal drugs (e.g., albendazole and praziquantel), and neurosurgical procedure, depending upon the situation. A patient of Asian origin came to our clinic with complaints of dizziness, headaches and episodes seizures for the past twelve years without proper diagnosis. The computed tomography and magnetic resonance imaging scans indicated multilobulated cystic mass in the brain with the suspicion of neurocysticercosis. PMID- 26851798 TI - Molecular evidence of two new species of Eleotris (Gobiiformes: Eleotridae) in the western Atlantic. AB - Fishes of the genus Eleotris present highly conserved morphology, which may make their recognition difficult. Here, two cryptic Eleotris lineages from five locations along the coast of Brazil were identified using the COI gene and two nuclear fragments. High bootstrap and posteriori values supported those lineages, and the genetic distance of COI varied from 6% between the two lineages to 14.1% from other western Atlantic Eleotris species, such as E. pisonis, E. amblyopsis and E. perniger. The reciprocal monophyly for both types of markers, the divergences between those lineages and the other Eleotris species from the Brazilian coast may, in fact, represent two new cryptic species. The cryptic lineages and currently recognized species were collected in distinct environments, reinforcing the need for further sampling to understand the real distribution of each taxon. PMID- 26851800 TI - Diagnostic usefulness of T-cell based assays for tuberculous meningitis in HIV uninfected patients. AB - OBJECTIVES: Early diagnosis and treatment of tuberculous meningitis (TBM) is essential for a positive outcome, but sensitive, specific, and rapid diagnostic tests for TBM are lacking. We evaluated the diagnostic utility of enzyme-linked immunosorbent spot (ELISPOT) assays in HIV-uninfected patients with suspected TBM. METHODS: All HIV-uninfected patients with suspected TBM were prospectively enrolled at a tertiary care hospital in an intermediate TB-burden country, during a 6-year period. ELISPOT assays were performed on peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid-mononuclear cells (CSF-MC). RESULTS: Of the 276 evaluable patients, 90 (33%) were classified as having TBM (30 definite cases, 19 probable, and 41 possible), and 186 (67%) as having non-TBM. When comparing definite TBM versus non-TBM, the sensitivity and specificity of the PBMC ELISPOT assay (>=6 spots; manufacturer's recommended cut-off) for diagnosing TBM were 96% (95% CI, 82-100) and 58% (95% CI, 50-66), respectively. The CSF-MC ELISPOT assay (>=38 spots; receiver operating characteristic [ROC]-derived cut off) was a useful rule-in test with specificity of 95% (96% CI, 90-98). Its sensitivity was 68% (95% CI, 45-86), which was superior those of AFB smear microscopy (14%; P < 0.001) and CSF Mycobacterium tuberculosis PCR (41%; P = 0.07). Combining this assay with M. tuberculosis PCR, clinical score, and both together increased sensitivity to 86%, 91%, and 95%, respectively, while retaining about 95% specificity. CONCLUSIONS: The CSF-MC ELISPOT assay appears to be a rapid and accurate rule-in test for the diagnosis of TBM and a useful adjunct for diagnosing TBM in HIV-uninfected patients. PMID- 26851799 TI - Blood Eosinophils and Outcomes in Severe Hospitalized Exacerbations of COPD. AB - BACKGROUND: Patients with moderate exacerbations of COPD and the eosinophilic phenotype have better outcomes with prednisolone. Whether this outcome is similar in patients hospitalized with a severe exacerbation of COPD is unclear. We investigated the rate of recovery of eosinophilic and noneosinophilic exacerbations in patients participating in a multicenter randomized controlled trial assessing health outcomes in hospitalized exacerbations. METHODS: Patients were recruited at presentation to the hospital with an exacerbation of COPD. They were stratified into groups according to eosinophilic exacerbations if the peripheral blood eosinophil count on admission was >= 200 cells/MUL and/or >= 2% of the total leukocyte count. Admission details, serum C-reactive protein levels, length of stay, and subsequent rehospitalization data were compared between groups. RESULTS: A total of 243 patients with COPD (117 men) with a mean age of 71 years (range, 45-93 years) were recruited. The inpatient mortality rate was 3% (median time to death, 12 days; range, 9-16 days). The median absolute eosinophil count was 100 cells/MUL (range, 10-1,500 cells/MUL), and 25% met our criteria for an eosinophilic exacerbation; in this population, the mean length of stay (in days) was shorter than in patients with noneosinophilic exacerbations (5.0 [range, 1-19] vs 6.5 [range, 1-33]; P = .015) following treatment with oral corticosteroids and independent of treatment prior to admission. Readmission rates at 12 months were similar between groups. CONCLUSIONS: The study patients presenting to the hospital with a severe eosinophilic exacerbation of COPD had a shorter length of stay. The exacerbations were usually not associated with elevated C-reactive protein levels, suggesting that better treatment stratification of exacerbations can be used. TRIAL REGISTRY: http://www.isrctn.com/ISRCTN05557928. PMID- 26851801 TI - BRAF Inhibitors and IFNalpha: Plus, Minus, or Indeterminate? PMID- 26851803 TI - One good DNA-damage deserves another: Oxaliplatin in MSI-high colon cancer. PMID- 26851804 TI - Why can't the aortic valve be more like the mitral? PMID- 26851802 TI - Antitumor Activity of BRAF Inhibitor and IFNalpha Combination in BRAF-Mutant Melanoma. AB - BACKGROUND: BRAF(V600E)-mediated MAPK pathway activation is associated in melanoma cells with IFNAR1 downregulation. IFNAR1 regulates melanoma cell sensitivity to IFNalpha, a cytokine used for the adjuvant treatment of melanoma. These findings and the limited therapeutic efficacy of BRAF-I prompted us to examine whether the efficacy of IFNalpha therapy of BRAF(V600E) melanoma can be increased by its combination with BRAF-I. METHODS: BRAF/NRAS genotype, ERK activation, IFNAR1, and HLA class I expression were tested in 60 primary melanoma tumors from treatment-naive patients. The effect of BRAF-I on IFNAR1 expression was assessed in three melanoma cell lines and in four biopsies of BRAF(V600E) metastases. The antiproliferative, pro-apoptotic and immunomodulatory activity of BRAF-I and IFNalpha combination was tested in vitro and in vivo utilizing three melanoma cell lines, HLA class I-MA peptide complex-specific T-cells and immunodeficient mice (5 per group for survival and 10 per group for tumor growth inhibition). All statistical tests were two-sided. Differences were considered statistically significant when the P value was less than .05. RESULTS: The IFNAR1 level was statistically significantly (P < .001) lower in BRAF(V600E) primary melanoma tumors than in BRAF wild-type tumors. IFNAR1 downregulation was reversed by BRAF-I treatment in the three melanoma cell lines (P <= .02) and in three out of four metastases. The IFNAR1 level in the melanoma tumors analyzed was increased as early as 10 to 14 days following the beginning of the treatment. These changes were associated with: 1) an increased susceptibility in vitro of melanoma cells to the antiproliferative (P <= .04), pro-apoptotic (P <= .009) and immunomodulatory activity, including upregulation of HLA class I antigen APM component (P <= .04) and MA expression as well as recognition by cognate T-cells (P < .001), of BRAF-I and IFNalpha combination and 2) an increased survival (P < .001) and inhibition of tumor growth of melanoma cells (P < .001) in vivo by BRAF I and IFNalpha combination. CONCLUSIONS: The described results provide a strong rationale for the clinical trials implemented in BRAF(V600E) melanoma patients with BRAF-I and IFNalpha combination. PMID- 26851805 TI - Corrigendum to 'Morphological and functional consequences of transradial coronary angiography on the radial artery: implications for its use as a bypass conduit' [Eur J Cardiothorac Surg 2015;48:370-4]?. PMID- 26851806 TI - Corrigendum to 'Statistical and data reporting guidelines for the European Journal of Cardio-Thoracic Surgery and the Interactive CardioVascular and Thoracic Surgery' [Eur J Cardiothorac Surg 2015;48:180-93]?. PMID- 26851807 TI - Multiple arterial aneurysms in a patient with Behcet's disease. PMID- 26851808 TI - A novel approach to detect phrenic nerve stimulation in cardiac resynchronization therapy. PMID- 26851809 TI - Leadless pacemakers and MRI compatibility: authors' reply. PMID- 26851810 TI - Catheter ablation of multiple accessory pathways in Ebstein anomaly guided by intracardiac echocardiography. PMID- 26851811 TI - Retrieval of Medtronic Micra Transcatheter Pacing System after tether removal. PMID- 26851812 TI - An important advantage of the leadless pacemakers: magnetic resonance imaging compatibility. PMID- 26851813 TI - Yield of screening for atrial fibrillation in primary care with a hand-held, single-lead electrocardiogram device during influenza vaccination. AB - AIMS: To assess the yield of screening for atrial fibrillation (AF) with a hand held single-lead electrocardiogram (ECG) device during influenza vaccination in primary care in the Netherlands. METHODS AND RESULTS: We used the MyDiagnostick to screen for AF in persons who participated in influenza vaccination sessions of ten Dutch primary care practices. In case of suspected AF detection by the stick, the recorded 1-min ECG registrations were analysed by a cardiologist. We scrutinized electronic medical files of the general practitioners to obtain information about the cases screened. Multivariable logistic regression analysis was performed to predict the relation between patient characteristics and a new screen-detected diagnosis of AF. In total, 3269 persons were screened for AF during the influenza vaccination sessions of 10 general practitioner practices. As a result, 37 (1.1%) new cases of AF were detected. Prior transient ischeamic attack or stroke (OR 6.05; 95%CI 1.93-19.0), and age (OR 1.09 per year; 95% CI 1.05-1.14) were independent predictors for such newly screen-detected AF. Of the 37 screen-detected AF cases, 2.7% had a CHA2DS2-VASc of 0, 18.9% a score of 1, and 78.4% a score of 2 or more. The majority needed oral anticoagulant therapy. CONCLUSIONS: Screening seems feasible with an easy to use single-lead, hand-held ECG device with automatic AF detection during influenza vaccination in primary care and results in a '1-day' yield of 1.1% new cases of AF. TRIAL REGISTRATION CLINICALTRIALSGOV: NCT02006524. PMID- 26851814 TI - Effects of right ventricular pacing sites on blood pressure variation in upright posture: a comparison of septal vs. apical pacing sites. AB - AIMS: Large variations in blood pressure (BP) in the upright position are a major cause of pacemaker syndrome, observed in up to 80% of patients paced non physiologically at the right ventricular (RV) apex. We hypothesized that the magnitude of BP variations might be influenced by the RV pacing site. To assess this, we compared haemodynamic findings during supine and upright posture with RV apical vs. septal pacing. METHODS AND RESULTS: The study population comprised a retrospective cohort of 24 dual-chamber pacemaker patients with advanced or complete atrioventricular block, in which 11 were randomly chosen from those with RV apical pacing, and 13 randomly chosen from those with septal pacing. Studies were performed during fixed rate VVI and DDD pacing modes with patients in both supine and passive head-up tilt positions. Continuous BP, stroke volume, cardiac index, and total peripheral resistance index were measured non-invasively. During RV apical pacing, there were significant differences of beat-to-beat BP variation after movement from supine to upright posture for both VVI and DDD pacing modes (P < 0.05); however, this was not the case for either mode during RV septal pacing. Further, comparing RV apical to RV septal pacing in the supine position, there were no BP variation differences for either DDD or VVI modes. Conversely, in the upright position BP variation was significantly greater during RV apical vs. RV septal VVI pacing (P = 0.017) but not during DDD pacing. CONCLUSION: During VVI pacing, RV septal pacing exhibited lesser BP variation during upright posture compared with RV apical pacing. PMID- 26851815 TI - Syncope in patients paced for atrioventricular block. AB - AIMS: Although syncope is the main reason for cardiac pacing in ~40% of patients affected by atrioventricular block (AVB), very few data are available on the benefit of cardiac pacing in preventing syncopal recurrences. METHODS AND RESULTS: We retrospectively evaluated 229 consecutive patients (124 males, age 80 +/- 10 years) who had received a permanent pacemaker from January 2009 to December 2013 for AVB and syncope (94 patients, 41%) or AVB without syncope (135 patients, 59%). In patients with AVB and syncope, a third-degree or Mobitz II second-degree AVB had been documented in 73 and was only suspected in another 21, all of whom had bundle branch block. Follow-up was available in 223 patients. At 5 years, the actuarial syncope recurrence rate was 1% (95% CI, 0-3) in patients with documented AVB plus syncope and 3% (95% CI, 1-5) in those without syncope, whereas it was 14% (95% CI, 0-28) in patients with undocumented AVB plus syncope (P = 0.001). The actuarial combined recurrence rate of syncope and/or pre-syncope was 2% (95% CI, 0-4) in patients without syncope, 8% (95% CI, 0-17) in patients with documented AVB plus syncope, and 19% (95% CI, 1-37) in patients with undocumented AVB plus syncope, P = 0.002. All syncopes occurred in patients without overt structural heart disease (SHD), the corresponding actuarial estimate being 4% (95% CI, 0-6) at 1 year and 6% (95% CI, 4-8) at 5 years (P = 0.002 vs. patients with SHD). CONCLUSIONS: Cardiac pacing is highly effective in preventing syncopal recurrences when AVB is documented. Syncope may recur in a non-negligible minority of paced patients when AVB is suspected but not documented and in patients without SHD. PMID- 26851816 TI - Geographical variation in the prevalence of heavy drinking in young Swiss men. AB - BACKGROUND: Not much is known about how much geographical units matter for heavy alcohol consumption and how much of the geographical variations are explained by characteristics such as institutional alcohol policies and regional economic conditions. The study aim was to address these gaps considering three types of heavy alcohol consumption. METHODS: Analyses were based on data collected on 5879 men (age: 20.0 years, standard deviation: 1.2) years participating in the Cohort Study on Substance Use Risk Factors in Switzerland. Generalized linear mixed models were used to assess overall prevalence, geographical variations in prevalence across geographical units (institutional units, economic micro regions, linguistic regions, urban/rural status), and explanatory variables in three different types of heavy alcohol consumption (heavy weekend drinking, heavy workweek drinking, heavy volume drinking). RESULTS: The overall prevalence for heavy weekend drinking was 46.8%, 10.8% for heavy volume drinking and 3.6% for heavy workweek drinking. The extent and locations of geographical variation in prevalence rates were contingent upon the type of alcohol consumption. Institutional alcohol policies explained substantial geographical variations in heavy weekend drinking, but not in heavy workweek or heavy volume drinking. Regional economic conditions were not related to alcohol consumption. CONCLUSIONS: Different types of heavy alcohol consumption are determined by different geographical units. Alcohol policies protectively impact the major drinking style of heavy weekend drinking, but not other low prevalence forms of heavy drinking. Research and public health efforts must take into account these differences between types of alcohol consumption. PMID- 26851817 TI - The association between accessibility of local convenience stores and unhealthy diet. AB - BACKGROUND: High accessibility of unhealthy food stores may contribute to a poor dietary quality. Research on the link between neighbourhood food environment and consumption is limited, especially in a European context. The objective of this study was to examine the relationship between convenience stores (CS) and dietary quality within the Capital Region of Denmark. METHOD: Cross-sectional study of the geographic food environment in the Capital Region of Denmark based on 47 623 subjects (age 16+ years) with complete information on retail food environment and dietary quality. A categorization procedure to identify CS from a government list of inspected food stores (the Smiley register) was developed. Using GIS network analyses, density of CS within 0.25 km and 0.5 km network buffers from residency was calculated for participants in metropolitan and non-metropolitan areas, respectively. Information on dietary intake and confounders is derived from a questionnaire survey. Multi-level analyses were performed, adjusting for age, sex, individual socio-economic factors and area socio-economic status. RESULTS: In the non-metropolitan population, the odds of having an unhealthy diet increased significantly (P < 0.0001) with increased density of CS. Compared to individuals who did not have a CS within 0.5 km from their home, the odds ratios were 1.20 (95% CI: 1.09-1.33) and 1.37 (95% CI: 1.19-1.57) for individuals having 1 or >=2 CS, respectively. In the fully adjusted model, the overall association remained significant (P = 0.015) and odds ratios diminished to 1.14 (1.02-1.27) and 1.18 (1.01-1.38). CONCLUSION: High accessibility of CS in neighbourhoods is associated with less healthy dietary habits among residents. PMID- 26851818 TI - Limited evidence suggests higher risk of dental implant failures in smokers than in nonsmokers. PMID- 26851819 TI - Endobiliary hepatocellular carcinoma: A rare tumor mimicking cholangiocarcinoma. PMID- 26851820 TI - Seasonality and temperature effects on fasting plasma glucose: A population-based longitudinal study in China. AB - AIMS: To examine the seasonality and effects of temperature on levels of fasting plasma glucose (FPG). METHODS: We collected health data from the Kailuan cohort study. FPG, blood pressure and individual information including age, gender, body mass index, smoking status, drinking habit, physical activities, income, work type, education level, and history of diabetes, were collected for each participant. Daily weather conditions were collected during the study period of 2006-2011. A total of 49,417 participants who had three times of health examination were included to the analyses. Generalized additive mixed models were used to examine the effects of temperature and seasonality on FPG levels, while controlling for potential confounders. RESULTS: FPG level was higher in winter and spring than that in autumn and summer. For all participants, the FPG winter level increased 0.31mmol/L [95% confidence interval (CI), 0.28-0.33mmol/L] in comparison with autumn. The association between temperature and FPG levels was U shaped. For all participants, the change in FPG levels associated with extreme cold temperature (-6.7 degrees C), moderate cold temperature (2.4 degrees C), moderate hot temperature (23.7 degrees C), and with extreme hot temperature (28.1 degrees C), in comparison with threshold (18.1 degrees C) were 0.12mmol/L (95% CI: 0.10-0.14mmol/L), 0.10 (95% CI: 0.09-0.12mmol/L), 0.06 (95% CI: 0.04 0.08mmol/L), and 0.12mmol/L (95% CI: 0.08-0.16mmol/L), respectively. CONCLUSION: The findings suggest that there may be strong relationships between FPG levels and season and ambient temperature. In particular, there were higher FPG levels in the winter and at extreme cold and hot temperatures. PMID- 26851822 TI - Synthesis of lanthanum aluminate by reverse chemical precipitation using pseudoboehmite as alumina precursor. AB - Lanthanum aluminate was synthesized by using reverse precipitation. A lanthanum nitrate salt in solution allowed the precipitation of lanthanum hydroxide onto the surface of the pseudoboehmite particles. Pseudoboehmite was previously synthesized out of aluminum sulfate which after characterization presents a poor crystallized structure. A Perovskite-type lanthanum aluminate was obtained at different temperature and calcination time. When calcination was set up to 1500 degrees C to 3 degrees C/min pure, high crystallinity and highly agglomerated lanthanum aluminate is obtained, relative density of 94% was reached. PMID- 26851821 TI - Bacterial resistance in urinary tract infections in patients with diabetes matched with patients without diabetes. AB - BACKGROUND: With bacterial resistances having increased, patients with diabetes who are at higher risk of urinary tract infection (UTI) need to be studied. The study aim was to compare bacterial resistances to ofloxacin, cefixim, co trimoxazole, nitrofurantoin and fosfomycin in UTI between patients with and without diabetes. METHODS: A cross-sectional study was conducted in ambulatory laboratories, including patients over 18 coming for urinalyses. Patients with diabetes were matched with two patients without diabetes based on risk factors for UTI using a propensity score. RESULTS: Among 1119 patients with UTI, 124 patients with diabetes were matched with 246 patients without diabetes. In patients with diabetes, the bacteria identified were: Escherichia coli (71%), Klebsiella (6%), Staphylococcus (5%), Enterococcus (4%), Proteus (2%) and Pseudomonas (1%); these findings were similar to those found in patients without diabetes. Resistances to ofloxacin and cefixim regardless of the bacteria were increased in patients with diabetes after matching on age, sex and history of UTI (respectively: OR=2.09; p=0.04 and OR=3.67; p=0.05). Regarding E. coli resistance, there was no difference whatever the antibiotic. CONCLUSION: The increased ofloxacin and cefixim resistance in patients with diabetes should be considered when prescribing probabilistic antibiotics, and could lead to changes in first-line treatments in UTI. PMID- 26851823 TI - Measurement of (222)Rn by absorption in plastic scintillators and alpha/beta pulse shape discrimination. AB - This work demonstrates that common plastic scintillators like BC-400, EJ-200 and SCSF-81 absorb radon and their scintillation pulse decay times are different for alpha- and beta-particles. This allows the application of pulse shape analysis for separation of the pulses of alpha- and beta-particles emitted by the absorbed radon and its progeny. It is shown that after pulse shape discrimination of beta particles' pulses, the energy resolution of BC-400 and EJ-200 alpha spectra is sufficient to separate the peaks of (222)Rn, (218)Po and (214)Po and allows (222)Rn measurements that are unaffected by the presence of thoron ((220)Rn) in the environment. The alpha energy resolution of SCSF-81 in the experiments degrades due to imperfect collection of the light emitted inside the scintillating fibers. The experiments with plastic scintillation microspheres (PSM) confirm previous findings of other researchers that PSM have alpha-/beta discrimination properties and show suitability for radon measurements. The diffusion length of radon in BC-400 and EJ-200 is determined. The pilot experiments show that the plastic scintillators are suitable for radon-in-soil gas measurements. Overall, the results of this work suggest that it is possible to develop a new type of radon measurement instruments which employ absorption in plastic scintillators, pulse-shape discrimination and analysis of the alpha spectra. Such instruments can be very compact and can perform continuous, real time radon measurements and thoron detection. They can find applications in various fields from radiation protection to earth sciences. PMID- 26851824 TI - Prevalence of cerebral palsy and intellectual disability among children identified in two U.S. National Surveys, 2011-2013. AB - PURPOSE: Cerebral palsy (CP) and intellectual disability (ID) are developmental disabilities that result in considerable functional limitations. There are few recent and nationally representative prevalence estimates of CP and ID in the United States. METHODS: We used two U.S. nationally representative surveys, the 2011-2012 National Survey of Children's Health (NSCH) and the 2011-2013 National Health Interview Survey (NHIS), to determine the prevalence of CP and ID based on parent report among children aged 2-17 years. RESULTS: CP prevalence was 2.6 (95% confidence interval [CI]: 2.1-3.2) per 1000 in the NSCH and 2.9 (95% CI: 2.3-3.7) in the NHIS. ID prevalence was 12.2 (95% CI: 10.7-13.9) and 12.1 (95% CI: 10.8 13.7) in NSCH and NHIS, respectively. For both conditions, the NSCH and NHIS prevalence estimates were similar to each other for nearly all sociodemographic subgroups examined. CONCLUSIONS: Despite using different modes of data collection, the two surveys produced similar and plausible estimates of CP and ID and offer opportunities to better understand the needs and situations of children with these conditions. PMID- 26851825 TI - The impact of continuity of care on emergency room use in a health care system without referral management: an instrumental variable approach. AB - PURPOSE: The purpose of the study was to determine whether continuity of care (COC) is beneficial in national health care systems without referral management by controlling for endogeneity of COC. METHODS: We used National Health Insurance (Taiwan) claims data from 2008, encompassing approximately 23 million people, to determine whether COC is associated with reduced emergency room (ER) use by hypertension and diabetic patients in 2009. We used an instrumental variable approach to account for endogeneity associated with patients' COC levels. RESULTS: After controlling for endogeneity, the marginal effect of COC on ER use probability when the COC score increased from 0 to 1 was 7.6% (P < .001) and 14.8% (P < .001) for hypertension and diabetic patients, respectively. CONCLUSIONS: We determined that COC is more effective for reducing ER use than are models that assume that COC is exogenous. It has been argued that in many countries, health care systems without referral management encourage physician shopping and hinder physician-patient communication. However, there are benefits to disease-specific COC. Because current estimations have failed to take endogeneity biases into account, COC is more effective than is currently assumed. PMID- 26851826 TI - Concordant utrophin upregulation in phenotypically discordant DMD/BMD brothers. AB - Utrophin expression was investigated in two phenotypically discordant Duchenne muscular dystrophy half-brothers. The youngest was wheelchair-bound at age 9, while his mildly affected older brother was able to walk without difficulties at age 15. DNA analysis revealed an out-of-frame exon 2 duplication in the DMD gene, associated with muscle dystrophin protein deficiency. Utrophin localization and quantity was analyzed and compared in both sibs to verify whether this could explain the milder phenotype of the older brother. Immunofluorescence analysis showed a clear sarcolemmal labeling for utrophin in both of them, which was present in regenerating as well as in mature fibers. On western blot analysis, utrophin amount was increased 3.4 and 3.3 fold respectively, as compared to normal controls, while it was increased 1.7 to 4.0 fold in a group of DMD patients within the typical range of clinical progression. These data are in accordance with our previous observations suggesting no correlation between phenotype severity and utrophin up-regulation or sarcolemmal localization in dystrophinopathies. Finding the protective mechanisms in patients with milder course is of utmost interest to direct therapeutic targets. PMID- 26851827 TI - The role of substance P in the maintenance of colonic hypermotility induced by repeated stress in rats. AB - BACKGROUND: The mechanism underlying chronic stress-induced gastrointestinal (GI) dysmotility has not been fully elucidated and GI hormones have been indicated playing a role in mediating stress-induced changes in GI motor function. AIMS: Our objective was to study the possible role of substance P (SP) in the colonic hypermotility induced by repeated water avoidance stress (WAS) which mimics irritable bowel syndrome. METHODS: Male Wistar rats were submitted to WAS or sham WAS (SWAS) (1h/day) for up to 10 consecutive days. Enzyme Immunoassay Kit was used to detect the serum level of SP. The expression of neurokinin-1 receptor (NK1R) was investigated by Immunohistochemistry and Western blotting. The spontaneous contraction of muscle strip was studied in an organ bath system. L type calcium channel currents (ICa,L) of smooth muscle cells (SMCs) were recorded by whole-cell patch-clamp technique. RESULTS: Fecal pellet expulsion and spontaneous contraction of proximal colon in rats were increased after repeated WAS. The serum level of SP was elevated following WAS. Immunohistochemistry proved the expression of NK1R in mucosa, muscularis and myenteric plexus. Western blotting demonstrated stress-induced up-regulation of NK1R in colon devoid of mucosa and submucosa. Repeated WAS increased the contractile activities of longitudinal muscle and circular muscle strips induced by SP and this effect was reversed by a selective NK1R antagonist. The ICa,L of SMCs in the WAS rats were drastically increased compared to controls after addition of SP. CONCLUSIONS: Increased serum SP level and up-regulated NK1R in colon may contribute to stress induced colonic hypermotility. And L-type calcium channels play a potentially important role in the process of WAS-induced dysmotility. PMID- 26851828 TI - The genomics of prematurity in an era of more precise clinical phenotyping: A review. AB - Spontaneous preterm birth is a major public health problem, with a clear genetic component. Genetic association studies have evolved substantially in recent years, moving away from the traditional candidate gene analyses to newer approaches utilizing sophisticated analysis platforms to examine sequencing data, and shifting towards functional studies including methylation analysis. It is becoming increasingly evident that careful clinical phenotyping is crucial to high quality genetic association studies regardless of the assay or platform being used. Nonetheless, genetic studies of prematurity are hampered by numerous challenges including small sample sizes, incomplete phenotying, population stratification, and multiple comparisons. As the costs of sequencing and functional analyses continue to decrease, unbiased genome-wide assays will be more widely available. Researchers have met improved success recently when critically applying clinical phenotyping knowledge to group women prior to analyzing genotyping results. Eventually, as the analytic approaches evolve, it is likely that this methodology (combining precisely clinically phenotyped subjects with genome-wide data) will provide key information regarding the pathophysiology of prematurity, and provide potential new avenues for exploring innovative therapeutic strategies. PMID- 26851829 TI - Enhancing collaboration between China and African countries for schistosomiasis control. AB - Schistosomiasis remains an important public health issue, with a large number of cases reported across sub-Saharan Africa, and parts of Asia and Latin America. China was once highly endemic, but has made substantial progress and is moving towards elimination of schistosomiasis. Meanwhile, despite long-term, repeated, school-based chemotherapy in many African countries, more than 90% of all schistosomiasis cases are concentrated in Africa, and hence, this continent constitutes the key challenge for schistosomiasis control. Opportunities and issues for international collaboration in the fight against schistosomiasis are outlined with a focus on China's experiences, including the role of public health authorities and intersectoral collaboration, use of new and effective snail control approaches and diagnostic tools adapted to the specific stage of control, as well as the strengthening of risk mapping and surveillance-response mechanisms. Training courses targeting African governmental officials and professionals, coupled with field visits of African scientists and control programme managers to China, and vice versa, are considered important for improved schistosomiasis control and elimination. The crucial question remains whether the Chinese experience can be translated and applied in African countries to improve the effectiveness of health interventions and scale-up. PMID- 26851830 TI - Treatment of recalcitrant bullous pemphigoid (BP) with a novel protocol: A retrospective study with a 6-year follow-up. AB - BACKGROUND: Bullous pemphigoid is an autoimmune blistering skin disease that predominantly affects the elderly. Conventional therapy using high-dose systemic corticosteroids and immunosuppressive agents can be ineffective in some patients and produce adverse events and relapses. Hence, alternate therapies are required. OBJECTIVE: The clinical outcomes of patients with extensive, recalcitrant bullous pemphigoid treated with a combination therapy of rituximab (RTX) and intravenous immunoglobulin were evaluated. METHODS: In this retrospective study, 12 patients (mean age of 68.25 years) unresponsive to previous conventional immunosuppressive therapy, intravenous immunoglobulin, and/or RTX were treated with this combination therapy. RESULTS: Complete clinical resolution occurred in a mean of 4.6 months and previous systemic therapy was discontinued in 6.2 months. Two patients had a recurrence posttherapy and responded to additional RTX infusions. The remaining 10 patients had no recurrences. Patients were followed up for a mean of 73.8 months after discontinuation of all systemic therapy. All have remained in remission without adverse events for 6 years. LIMITATIONS: This was a retrospective study with a small sample size. CONCLUSION: The combination of RTX and intravenous immunoglobulin produced a sustained clinical remission without adverse events, infections, and hospitalizations. This specific combination protocol offers a promising therapy for patients with recalcitrant bullous pemphigoid. PMID- 26851831 TI - Distinguishing diffuse alopecia areata (AA) from pattern hair loss (PHL) using CD3(+) T cells. AB - BACKGROUND: Distinguishing between diffuse subacute alopecia areata (AA), in which the peribulbar infiltrate is absent, and pattern hair loss is challenging, particularly in cases that lack marked follicular miniaturization and a marked catagen/telogen shift. OBJECTIVE: We sought to distinguish diffuse AA from pattern hair loss using CD3(+) T lymphocytes. METHODS: A total of 28 cases of subacute AA and 31 cases of pattern hair loss were selected and a 4-mm punch biopsy was performed. All the specimens were processed using the "HoVert" (horizontal and vertical) technique. In all cases, hematoxylin-eosin and immunohistochemical stains for CD3, CD4, CD8, and CD20 were performed. RESULTS: The presence of CD3(+) lymphocytes within empty follicular fibrous tracts (stela), even without a concomitant peribulbar infiltrate, is a reliable histopathological clue in supporting a diagnosis of AA (sensitivity 0.964, specificity 1, P <= .001). LIMITATIONS: Limited tissue for analysis remained in the clinical sample tissue blocks. CONCLUSION: The presence of CD3(+) T-cells within empty follicular fibrous tracts (stela) supports a diagnosis of AA. PMID- 26851832 TI - How should we analyze and present mortality in our patients?: A multicentre GCDP experience. AB - INTRODUCTION: There are different strategies to analyse mortality in peritoneal dialysis (PD) with different definitions for case, event, time at risk, and statistical tests. A common method for the different registries would enable proper comparison to better understand the actual differences in mortality of our patients. METHODS: We review and describe the analysis strategies of regional, national and international registries. We include actuarial survival, Kaplan Meier (KM) and competitive risk (CR) analyses. We apply different approaches to the same database (GCDP), which show apparent differences with each method. RESULTS: A total of 1,890 incident patients in PD from 2003-2013 were included (55 years; men 64.2%), with initial RRF of 7ml/min; 25% had diabetes and a Charlson index of 3 [2-4]; 261 patients died, 380 changed to haemodialysis (HD) and 682 received a transplant. Annual mortality rates varied up to 20% in relative numbers (6.4 vs. 5.2%) depending on the system applied. The estimated probability of mortality measured by CR progressively differs from the KM over the years: 3.6 vs. 4.0% the first year, then 9.0 vs. 11.9%, 15.6 vs. 28.3%, and 18.5 vs. 43.3% the following years. CONCLUSIONS: Although each method may be correct in themselves and express different approaches, the final impression left on the reader is a number that under/overestimates mortality. The CR model better expresses the reality of PD, where the number of patients lost to follow-up (transplant, transfer to HD) it is 4 times more than deceased patients and only a quarter remain on PD at the end of follow up. PMID- 26851833 TI - Unsupervised entity and relation extraction from clinical records in Italian. AB - This paper proposes and discusses the use of text mining techniques for the extraction of information from clinical records written in Italian. However, as it is very difficult and expensive to obtain annotated material for languages different from English, we only consider unsupervised approaches, where no annotated training set is necessary. We therefore propose a complete system that is structured in two steps. In the first one domain entities are extracted from the clinical records by means of a metathesaurus and standard natural language processing tools. The second step attempts to discover relations between the entity pairs extracted from the whole set of clinical records. For this last step we investigate the performance of unsupervised methods such as clustering in the space of entity pairs, represented by an ad hoc feature vector. The resulting clusters are then automatically labelled by using the most significant features. The system has been tested on a fairly large data set of clinical records in Italian, investigating the variation in the performance adopting different similarity measures in the feature space. The results of our experiments show that the unsupervised approach proposed is promising and well suited for a semi automatic labelling of the extracted relations. PMID- 26851835 TI - 2-Oxo-1,2-dihydropyridinyl-3-yl amide-based GPa inhibitors: Design, synthesis and structure-activity relationship study. AB - Glycogen phosphorylase (GP), which plays a crucial role in the conversion of glycogen to glucose-1-phosphate, is a target for therapeutic intervention in diabetes. In this study, we report the design and synthesis of 29 new derivatives of 2-oxo-1,2-dihydro pyridin-3-yl amides, as potential inhibitors of GP. The hit rate (45%) was high with 13 compounds inhibiting GPa (between 33% at 4.40 mM and an IC50 of 1.92 MUM). Two lead compounds were identified as compounds exhibiting good GPa inhibition (IC50 = 2.1 and 1.92 MUM). SAR analysis of these compounds revealed sensitivity of GPa to the length of the 2-oxo-1,2-dihydro pyridin-3-yl amide derivative and a preference for inclusion of a 3,4-dichlorobenzyl moiety. PMID- 26851836 TI - Disgust stimuli reduce heart rate but do not contribute to vasovagal symptoms. AB - BACKGROUND AND OBJECTIVES: The vasovagal response demonstrates a unique form of stress response, common in medical settings yet provoked by a variety of blood injury-injection stimuli. This study aimed to better understand the psychophysiological mechanisms of the vasovagal response.. METHODS: 16 undergraduates with and 42 without a self-reported history of fainting watched five 3-5 min videos with different emotional content. One documentary clip (Neutral condition) described a campus environmental project while another (Blood/Injury) depicted portions of an open heart surgery. Three additional clips were also used, including Medical, Threat, and Contamination stimuli. Vasovagal symptoms and physiological variables were assessed during each video. RESULTS: As predicted, while the disgust-related stimuli (Blood/Injury, Medical, Contamination) were associated with generally lower heart rate, the Blood/Injury video produced the highest symptoms and the only significant difference between previous fainters and non-fainters. The physiological measures also revealed that participants with a fainting history experienced higher stroke volume and lower systolic blood pressure throughout, as well as several main effects of video. LIMITATIONS: An additional decrease in systolic blood pressure and respiration produced by watching the Blood/Injury video may have been sufficient to trigger symptoms in some, though results also suggest that systemic variables do not entirely explain susceptibility to symptoms. More careful evaluation of regional blood flow may be required. CONCLUSIONS: Participants who had previously experienced strong vasovagal responses displayed what appeared to be an anticipatory response to the Blood/Injury video. Finally, disgust stimuli may reduce heart rate but do not appear to contribute to vasovagal symptoms. PMID- 26851834 TI - The 5-HT1A receptor in Major Depressive Disorder. AB - Major Depressive Disorder (MDD) is a highly prevalent psychiatric diagnosis that is associated with a high degree of morbidity and mortality. This debilitating disorder is currently one of the leading causes of disability nationwide and is predicted to be the leading cause of disease burden by the year 2030. A large body of previous research has theorized that serotonergic dysfunction, specifically of the serotonin (5-HT) 1A receptor, plays a key role in the development of MDD. The purpose of this review is to describe the evolution of our current understanding of the serotonin 1A (5-HT1A) receptor and its role in the pathophysiology MDD through the discussion of animal, post-mortem, positron emission tomography (PET), pharmacologic and genetic studies. PMID- 26851837 TI - Aerobic bacterial catabolism of persistent organic pollutants - potential impact of biotic and abiotic interaction. AB - Several aerobic bacteria possess unique catabolic pathways enabling them to degrade persistent organic pollutants (POPs), including polychlorinated dibenzo-p dioxins/furans (PCDD/Fs), polybrominated diphenylethers (PBDEs), and polychlorinated biphenyls (PCBs). The catabolic activity of aerobic bacteria employed for removal of POPs in the environment may be modulated by several biotic (i.e. fungi, plants, algae, earthworms, and other bacteria) and abiotic (i.e. zero-valent iron, advanced oxidation, and electricity) agents. This review describes the basic biochemistry of the aerobic bacterial catabolism of selected POPs and discusses how biotic and abiotic agents enhance or inhibit the process. Solutions allowing biotic and abiotic agents to exert physical and chemical assistance to aerobic bacterial catabolism of POPs are also discussed. PMID- 26851838 TI - The effect of bergamot on dyslipidemia. AB - BACKGROUND: Statins are the most common used lipid lowering drugs but they may cause adverse effects and despite their well-established therapeutic benefits residual cardiovascular (CV) risk remains. The use of other lipid lowering drugs and nutraceuticals alone or as add-on lipid-modifying therapy can be an option in such cases. Several studies have reported health-related properties of the Citrus fruits, among which bergamot (Citrus bergamia Risso) differs from others by particularly high content of certain compounds. PURPOSE: This narrative review summarizes the current evidence on the effects of bergamot on lipid parameters based on studies involving animals and humans. MAIN EVIDENCE: This natural supplement may lead to effective lipid-lowering treatment. Its lipid-lowering activity is attributed to different flavonoids. However, the exact mechanisms involved remain unclear. CONCLUSION: It is expected that ongoing and future studies will confirm the benefit of bergamot in dyslipidemic and other cardiometabolic disorders, potentially leading to reduced overall CV risk. PMID- 26851840 TI - An integrative approach to understanding pyrethroid resistance in Rhipicephalus microplus and R. decoloratus ticks. AB - Rhipicephalus microplus and Rhipicephalus decoloratus species occur in regions with savannah and temperate climates, typically in grassland and wooded areas used as cattle pasture. Both species are associated with the transmission of Anaplasma and Babesia spp., impacting livestock health and quality of livestock associated products. In Africa, tick control is predominantly mediated with the use of acaricides, such as synthetic pyrethroids. After several years on the market, reports of resistance to synthetic pyrethroids escalated but limited field data and validation studies have been conducted to determine the extent of acaricide resistance in Africa. Without this data, knowledge-based tick control will remain problematic and selection pressure will remain high increasing the rate of resistance acquisition. To date, several pyrethroid resistance associated single nucleotide polymorphisms (SNPs) have been reported for arthropods within the voltage-gated sodium channel. Three SNPs have been identified within this channel in pyrethroid resistant R. microplus ticks, but none has been reported for R. decoloratus. This study is the first to report the presence of a shared SNP within the voltage-gated sodium channel in both R. microplus and R. decoloratus, which is directly linked to pyrethroid resistance in R. microplus. As the mode of action by which these SNPs mediate pyrethroid resistance remains unknown, this study aims to set hypotheses by means of predictive structural modelling. This not only paves the way forward to elucidating the underlying biological mechanisms involved in pyrethroid resistance, but also improvement of existing acaricides and ultimately sustainable tick control management. PMID- 26851839 TI - Subclinical neurological involvement does not develop if Wilson's disease is treated early. AB - BACKGROUND & AIMS: Wilson's disease (WD) is a genetic disorder of copper metabolism causing dysfunctions of various organs, mostly the liver and brain. If untreated, WD is fatal, but early treatment results in a good prognosis, although the long-term neurological outcome has not yet been clarified. To address this issue, we evaluated the neurological status of early-treated WD patients without overt nervous system impairment using neurophysiological, neuropsychological and neuroimaging procedures at least 10 years after treatment onset. METHODS: Thirty eight WD patients (18 females, aged 24.47 +/- 7.50 years), who received an early diagnosis (in presymptomatic or mild/moderate liver disease stages without neurological involvement) and prompt treatment, were clinically evaluated with the Global Assessment Scale. Presentation was hepatic in 36 subjects (95%), while 2 patients (5%) were presymptomatic. A neurophysiological study was performed to explore the central motor conduction time of the upper and lower limbs, and motor cortex excitability using single pulses and paired-pulse transcranial magnetic stimulation. Neuroimages were obtained with brain magnetic resonance scans. Cognitive abilities, and psychiatric and behavioral disturbances were evaluated with neuropsychological tests. RESULTS: Patients were undergoing treatment with penicillamine (7 patients) or zinc salts (31 patients) with good adherence. They did not present any neurological signs at clinical evaluation or at specific scale of impairment, the mean Global Assessment Scale score was 0.3 +/- 0.7. Magnetic resonance imaging, transcranial magnetic stimulation studies and neuropsychological/neuropsychiatric assessment ruled out subclinical involvement. CONCLUSIONS: This study suggests that early diagnosis and treatment of WD may prevent the onset of neurologic damage, even at subclinical level. PMID- 26851841 TI - Response to the influenza vaccine based on estradiol use in menopausal women. AB - OBJECTIVE: To assess the impact of 17beta-estradiol in modulating the response to the influenza vaccine in postmenopausal women. METHODS: A prospective cohort study was conducted with 46 healthy postmenopausal women aged 41-62 years without previous vaccination against the influenza virus. Evaluation of serum antibodies using hemagglutination inhibition and single radial hemolysis was performed at the Virology Laboratory of the Butantan Institute, Sao Paulo, Brazil, using serum samples collected at two time points: immediately before and one month after vaccination. RESULTS: In non-estradiol users (n=25), the median number of hemagglutination-inhibiting units (Log2) increased from 5.32 to 6.82 (p=0.003). In estradiol users (n=21), the median number of hemagglutination-inhibiting units (Log2) increased from 5.32 to 5.82 (p=0.149). The median hemolytic areas produced with the single radial hemolysis assay before and after the vaccine were 11 mm in both groups. CONCLUSION: In postmenopausal women, estrogen therapy did not have a positive influence on the production of antibodies against the influenza virus after vaccination, at least based on the formulation, time period, and methods used for quantifying these antibodies in the present study. PMID- 26851842 TI - Identification of the risk factors associated with cheese production to implement the hazard analysis and critical control points (HACCP) system on cheese farms. AB - The purpose of this paper was to evaluate, by statistical analyses, risk factors on cheese farms that can influence the microbial contamination of their products. Various assessment tools, such as cheese production questionnaires, food handlers' knowledge testing, and hygiene assessment system surveys, were used on 39 cheese farms on the island of Gran Canaria, Spain. The microbiological status of 773 raw milk and cheese samples from the cheese farms was assessed by enumerating total viable counts and 4 pathogens: Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, and Salmonella spp. The results revealed that the highest contamination by Staph. aureus (4.39%, >10(5)cfu/mL) was found in milk, and the highest contamination by E. coli (5.18%, >10(3) cfu/mL) was found in cheese. Very few samples (0.52%) were contaminated by L. monocytogenes or Salmonella spp. The factors associated with any tested microorganism were "handling," "knowledge," and "type of milk." Subsequently, multidimensional logistic analysis for contamination by E. coli showed an independent association for factors "cleaning and disinfection test" and "type of milk." The probability of total aerobic contamination of milk increased with lower hygiene assessment system survey scores. These results emphasize the need to apply and maintain good hygiene practices, and to study risk factors to prevent contamination and bacterial growth. Further research is required in other areas with different cheese farm types to reinforce the validity of these results. PMID- 26851843 TI - Relationship between processing score and kernel-fraction particle size in whole plant corn silage. AB - Kernel processing increases starch digestibility in whole-plant corn silage (WPCS). Corn silage processing score (CSPS), the percentage of starch passing through a 4.75-mm sieve, is widely used to assess degree of kernel breakage in WPCS. However, the geometric mean particle size (GMPS) of the kernel-fraction that passes through the 4.75-mm sieve has not been well described. Therefore, the objectives of this study were (1) to evaluate particle size distribution and digestibility of kernels cut in varied particle sizes; (2) to propose a method to measure GMPS in WPCS kernels; and (3) to evaluate the relationship between CSPS and GMPS of the kernel fraction in WPCS. Composite samples of unfermented, dried kernels from 110 corn hybrids commonly used for silage production were kept whole (WH) or manually cut in 2, 4, 8, 16, 32 or 64 pieces (2P, 4P, 8P, 16P, 32P, and 64P, respectively). Dry sieving to determine GMPS, surface area, and particle size distribution using 9 sieves with nominal square apertures of 9.50, 6.70, 4.75, 3.35, 2.36, 1.70, 1.18, and 0.59 mm and pan, as well as ruminal in situ dry matter (DM) digestibilities were performed for each kernel particle number treatment. Incubation times were 0, 3, 6, 12, and 24 h. The ruminal in situ DM disappearance of unfermented kernels increased with the reduction in particle size of corn kernels. Kernels kept whole had the lowest ruminal DM disappearance for all time points with maximum DM disappearance of 6.9% at 24 h and the greatest disappearance was observed for 64P, followed by 32P and 16P. Samples of WPCS (n=80) from 3 studies representing varied theoretical length of cut settings and processor types and settings were also evaluated. Each WPCS sample was divided in 2 and then dried at 60 degrees C for 48 h. The CSPS was determined in duplicate on 1 of the split samples, whereas on the other split sample the kernel and stover fractions were separated using a hydrodynamic separation procedure. After separation, the kernel fraction was redried at 60 degrees C for 48 h in a forced-air oven and dry sieved to determine GMPS and surface area. Linear relationships between CSPS from WPCS (n=80) and kernel fraction GMPS, surface area, and proportion passing through the 4.75-mm screen were poor. Strong quadratic relationships between proportion of kernel fraction passing through the 4.75-mm screen and kernel fraction GMPS and surface area were observed. These findings suggest that hydrodynamic separation and dry sieving of the kernel fraction may provide a better assessment of kernel breakage in WPCS than CSPS. PMID- 26851844 TI - Effects of dietary nitrogen levels and carbohydrate sources on apparent ruminal synthesis of some B vitamins in dairy cows. AB - Effects of nitrogen level and carbohydrate source on apparent ruminal synthesis (ARS) of thiamin, riboflavin, niacin, vitamin B6, folates, and vitamin B12 were evaluated using 4 lactating Holstein cows distributed in a 4 * 4 Latin square design with treatments following a 2 * 2 factorial arrangement. Cows were fitted with cannulas in the rumen and proximal duodenum. The treatments were 2 N levels and 2 carbohydrate sources. The diet with the high N level provided 14% crude protein, calculated to meet 110% of the protein requirements and an adequate supply in rumen-degradable protein, whereas the diet with the low N level contained 11% crude protein, calculated to meet 80% of the protein requirements with a shortage in rumen-degradable protein. Carbohydrate source treatments differed by their nature (i.e., high in starch from barley, corn, and wheat, or high in fiber from soybean hulls and dehydrated beet pulp). All 4 diets were isoenergetic, based on corn silage, and had the same forage-to-concentrate ratio (60:40, dry matter basis). Duodenal flow was determined using YbCl3 as a marker. Each B-vitamin ARS was calculated as duodenal flow minus daily intake. The intake of several B vitamins varied among treatments, but because the animals consumed a similar amount of feed every day (average of 20 kg of dry matter/d) the difference was mostly due to vitamin content of each ingredient and their relative proportion in the diets. Decreasing N concentration in the diet reduced vitamin B6 duodenal flow and increased its apparent ruminal degradation. It also decreased duodenal flow and ARS of folates. The high-starch diets increased duodenal flow and ruminal balance of riboflavin, vitamin B6, and folates, whereas the high-fiber diets increased vitamin B12 ARS and duodenal flow. These effects on apparent synthesis are possibly due to changes in ruminal fermentation. PMID- 26851845 TI - Is calcitonin an active hormone in the onset and prevention of hypocalcemia in dairy cattle? AB - The objective of this study was to assess the potential importance of calcitonin (CALC) in the onset of subclinical hypocalcemia (experiment 1) and in the physiological mechanisms underlying the prevention of bovine hypocalcemia under metabolic acidosis (experiments 2 and 3). In experiment 1, 15 Holstein cows naturally incurring subclinical hypocalcemia during the first 5d postpartum were classified as low subclinical hypocalcemia (LSH) when blood Ca concentrations were between 7.5 and 8.5mg/dL, or as high subclinical hypocalcemia (HSH) when blood Ca concentrations were between 6.0 and 7.6 mg/dL. Blood samples were taken daily from d -5 to 5 relative to parturition to determine concentrations of parathyroid hormone (PTH), CALC, and 1,25(OH)2D3. In experiment 2, 24 Holstein bulls (497 +/- 69 kg of body weight and 342 +/- 10.5d of age) were assigned to 2 treatments (metabolic acidosis or control). Metabolic acidosis was induced by an oral administration of ammonium chloride (2.5 mEq/d) during 10 d, and animals were slaughtered thereafter. Blood samples were collected before slaughter to determine CALC, PTH, 1,25(OH)2D3, and samples of urine, kidney, parathyroid, and thyroid glands were obtained immediately after slaughter to determine expression of several genes in these tissues. Last, in experiment 3, we tested the activity of CALC under metabolic acidosis in vitro using breast cancer cell (T47D) cultures. Although PTH tended to be greater in HSH than in LSH, the levels of 1,25(OH)2D3 were lower in HSH cows (experiment 1). Blood CALC concentration was not affected by the severity of subclinical hypocalcemia, but it was influenced by days from calving (experiment 1). The expression of PTH receptor (PTHR) in the kidney was increased under metabolic acidosis (experiment 2). Furthermore, the activity of CALC was impaired under acidic blood pH (experiment 3). In conclusion, the CALC rise in HSH cows after calving impaired the recovery of blood Ca concentrations because the PTHR response was not sufficient to activate 1,25(OH)2D3 and compensate for the CALC effect. Metabolic acidosis prevents hypocalcemia because the expression of PTHR is upregulated in the kidney, resulting in an increased PTH activity and a subsequent increase in 1,25(OH)2D3 serum concentrations. Moreover, an impairment of CALC activity at low pH enhances the hypercalcemic role of PTH. PMID- 26851846 TI - Effect of trace minerals and starch on digestibility and rumen fermentation in diets for dairy heifers. AB - The objective of this study was to evaluate the effect of different forms of trace minerals (TM) and the use of different starch levels in dairy heifer diets on rumen fermentation and digestibility. Eight rumen cannulated dairy heifers (15.4 +/- 0.8 mo of age and 438.31 +/- 18.08 kg of body weight) were subjected to a split-plot, 4 * 4 Latin square design with 19-d periods: 15d of adaptation and 4d of sampling. The whole-plot factor was type of TM; organic as proteinates (OTM) or inorganic sulfates (ITM), and the subplot was starch level (3.54, 12.95, 22.25, and 31.73%). Total collection of feces and urine was completed on d 15 to 19 to determine digestibility and TM excretion. Rumen contents were sampled on d 18 to 19 at 0, 1, 2, 4, 8, 12, 16, 20, and 22 h after feeding to measure pH and volatile fatty acid (VFA) concentrations. Plasma samples were collected to evaluate TM concentrations and enzymatic activity for ceruloplasmin, glutathione peroxidase, and superoxide dismutase. Starch level affected pH, individual VFA concentrations, and nutrient excretion. Trace mineral intake was lower for OTM compared with ITM. No effect of TM form on dry matter digestibility was detected, but as level of starch increased, diet dry matter digestibility increased. Rumen pH was lower for diets with OTM, which is consistent with higher total VFA production and butyrate proportion observed for heifers fed OTM diets. These variables may be explained by the higher bioavailability of OTM and faster utilization and fermentation by rumen microorganisms. Heifers that consumed ITM had higher moisture in feces and higher urine excretion, which increased total manure production. Total excretion of TM was not different by treatment. Blood plasma mineral concentration was not different between treatments except for Mn, which was higher for OTM. Enzymatic activity was not affected by treatments. Mineral intake was reduced and blood mineral levels were not different, suggesting enhanced absorption of OTM compared with ITM. In conclusion, based on rumen pH, VFA production, and plasma TM concentration, OTM may be more ruminally bioavailable and absorbed to a greater extent than ITM. Also, TM form affected fecal moisture and urine excretion, suggesting that ITM may stimulate water intake. PMID- 26851847 TI - Effective lactation yield: A measure to compare milk yield between cows with different dry period lengths. AB - To compare milk yields between cows or management strategies, lactations are traditionally standardized to 305-d yields. The 305-d yield, however, gives no insight into the combined effect of additional milk yield before calving, decreased milk yield after calving, and a possible shorter calving interval in the case of a shortened dry period. We aimed to develop a measure that would enable the comparison of milk yield between cows with different dry period (DP) lengths. We assessed the importance of accounting for additional milk yield before calving and for differences in calving interval. The 305-d yield was compared with a 365-d yield, which included additional milk yield in the 60 d before calving. Next, an effective lactation yield was computed, defined as the daily yield from 60d before calving to 60 d before the next calving, to account for additional milk yield before calving and for differences in calving interval. Test-day records and drying-off dates of 15 commercial farms were used to compute the 305-d, 365-d, and effective lactation yields for individual cows. We analyzed 817 second-parity lactations preceded by no DP, a short DP (20 to 40 d), or a conventional DP (49 to 90 d). Compared with cows with a conventional DP, the 305 d yield of cows with no DP was 7.0 kg of fat- and protein-corrected milk (FPCM) per day lower, and the 305-d yield of cows with a short DP was 2.3 kg of FPCM per day lower. Including additional milk yield before calving in the 365-d yield reduced this difference to 3.4 kg of FPCM per cow per day for cows with no DP and to 0.9 kg of FPCM per cow per day for cows with a short DP. Compared with cows with a conventional DP, median days open were reduced by 25d for cows with no DP and by 18d for cows with a short DP. Accounting for these differences in calving interval in the effective lactation yield further decreased yield reductions for cows with no DP or a short DP by 0.3 kg of FPCM per cow per day. At the herd level, estimated 365-d yield losses for cows with no DP or a short DP differed from effective lactation yield losses by 0.4 to -0.8 kg FPCM per cow per day. Accounting for additional milk yield before calving had a major and consistent effect on yield comparisons of cows with different DP lengths. The effect of correcting for calving interval was more variable between farms and will especially be important when calving interval is affected by DP length. PMID- 26851848 TI - Once-daily milking during late lactation in pasture-fed dairy cows has minor effects on feed intake, body condition score gain, and hepatic gene expression. AB - Milking cows once daily (1*) is a management practice occasionally used during mid/late lactation in pasture-based systems. It has been postulated that 1* milking will reduce dry matter intake (DMI) and increase body condition score (BCS) gain; however, this has not been quantified. Lactating, pregnant Holstein Friesian dairy cows (n=52) were allocated to either 1* or twice-daily (2*) milking in mid-January (summer, 175d in milk). To obtain accurate DMI measurements, cows underwent 4 periods in a Calan gate indoor feeding facility, interspersed with grazing outdoors. Milk production, body weight (BW), and BCS were recorded 2 wk before treatment start (-2 wk) and weekly thereafter. Blood variables were recorded at -2 wk and weekly when indoors. Liver was biopsied at 2, 2, and 10 wk, and hepatic gene expression measured using quantitative PCR. Milking cows 1* tended to lower DMI (17.8 vs. 18.2 kg of dry matter), but increased BCS gain (0.36 vs. 0.13 BCS units) and BW (546 vs. 533 kg) at wk 12 relative to 2*. The greater BCS and BW of cows milked 1* compared with 2* were reflected in lower plasma concentrations of nonesterified fatty acids and lower transcription of genes involved in the oxidation of fatty acids, indicating reduced release and processing of fatty acids. Cows milked 1* produced 20% less milk, and although milk fat and protein concentrations were increased relative to cows milked 2*, yields of fat and protein were 14 and 17% less, respectively. The reduction in milk production with 1* milking (14.1 vs. 16.8 kg/cow per d energy corrected milk) was accompanied by increases in blood concentrations of glucose and insulin, with a concurrent decrease in the transcription of the insulin receptor and gluconeogenic genes. These results indicate a coordinated response to reduce glucose production due to decreased mammary demand. Expression of 2 genes linked to inflammation and adipokine signaling was reduced in cows milked 1* and may indicate a lower inflammatory state in the liver of cows milked 1* in late lactation. No effect was found of milking frequency during late lactation on milk production in the subsequent lactation. In summary, although 1* milking tended to reduce DMI and increase BCS in late lactation, these effects were lower than what is commonly supposed in pasture-based dairy systems. The modest BCS gains need to be considered with the reduced milk production when adopting 1* milking as a management strategy. PMID- 26851849 TI - Future consequences of decreasing marginal production efficiency in the high yielding dairy cow. AB - The objectives were to examine the gross and marginal production efficiencies in high-yielding dairy cows and the future consequences on dairy industry profitability. Data from 2 experiments were used in across-treatments analysis (n=82 mid-lactation multiparous Israeli-Holstein dairy cows). Milk yields, body weights (BW), and dry matter intakes (DMI) were recorded daily. In both experiments, cows were fed a diet containing 16.5 to 16.6% crude protein and net energy for lactation (NEL) at 1.61 Mcal/kg of dry matter (DM). The means of milk yield, BW, DMI, NEL intake, and energy required for maintenance were calculated individually over the whole study, and used to calculate gross and marginal efficiencies. Data were analyzed in 2 ways: (1) simple correlation between variables; and (2) cows were divided into 3 subgroups, designated low, moderate, and high DMI (LDMI, MDMI, and HDMI), according to actual DMI per day: <= 26 kg (n=27); >26 through 28.2 kg (n=28); and >28.2 kg (n=27). The phenotypic Pearson correlations among variables were analyzed, and the GLM procedure was used to test differences between subgroups. The relationships between milk and fat corrected milk yields and the corresponding gross efficiencies were positive, whereas BW and gross production efficiency were negatively correlated. The marginal production efficiency from DM and energy consumed decreased with increasing DMI. The difference between BW gain as predicted by the National Research Council model (2001) and the present measurements increased with increasing DMI (r=0.68). The average calculated energy balances were 1.38, 2.28, and 4.20 Mcal/d (standard error of the mean=0.64) in the LDMI, MDMI, and HDMI groups, respectively. The marginal efficiency for milk yields from DMI or energy consumed was highest in LDMI, intermediate in MDMI, and lowest in HDMI. The predicted BW gains for the whole study period were 22.9, 37.9, and 75.8 kg for the LDMI, MDMI, and HDMI groups, respectively. The present study demonstrated that marginal production efficiency decreased with increasing feed intake. Because of the close association between production and intake, the principle of diminishing marginal productivity may explain why increasing milk production (and consequently increasing intake) does not always enhance profitability. To maintain high production efficiency in the future, more attention should be given to optimizing rather than maximizing feed intake, a goal that could be achieved by nutritional manipulations that would increase digestibility or by using a diet of denser nutrients that would provide all nutritional requirements from lower intake. PMID- 26851850 TI - Fatty acid profile of milk and Cacioricotta cheese from Italian Simmental cows as affected by dietary flaxseed supplementation. AB - The study aimed to determine the effects of adding flaxseed to the diet on the fatty acid profile of the milk of Italian Simmental cows and on the Cacioricotta cheese thereby produced. The experiment involved 24 Italian Simmental cows divided into 2 groups of 12 animals according to the diet fed: a control diet (CO) with no flaxseed supplementation, and a diet supplemented with whole flaxseed (FS). Milk yield and composition was not significantly changed by diet, whereas saturated fatty acids, monounsaturated fatty acids (MUFA), and polyunsaturated fatty acids (PUFA) were increased by flaxseed supplementation. Cows fed flaxseed showed higher percentages of long-chain fatty acids: in particular, linolenic acids, mainly represented by C18:3n-3, and n-3 series were higher in the FS group than in the CO group. The percentage of MUFA was higher by about 12% in FS than in CO, mainly due to the contribution of C18:1 cis-9. The percentage of conjugated linoleic acid (CLA) in milk was not significantly changed by flaxseed supplementation. Furthermore, atherogenic and thrombogenic indices were lower by about 30 and 16%, respectively, in the FS group compared with the CO group. The fatty acid profile of Cacioricotta cheese produced using Italian Simmental cow milk showed higher levels of MUFA, PUFA, and n-3, and improved atherogenic and thrombogenic indices in FS than in CO, confirming the ability to transfer beneficial molecules from milk into cheese. In particular, cheese-making technology contributed to the increased CLA content in Cacioricotta cheese. PMID- 26851851 TI - Morin suppresses inflammatory cytokine expression by downregulation of nuclear factor-kappaB and mitogen-activated protein kinase (MAPK) signaling pathways in lipopolysaccharide-stimulated primary bovine mammary epithelial cells. AB - Morin, a flavonoid isolated from Chinese herbs of the Moraceae family, has been reported to possess antiinflammatory activity. However, the effects of morin on mastitis have not been investigated. The present study was conducted to elucidate the antiinflammatory properties of morin on lipopolysaccharide (LPS)-stimulated primary bovine mammary epithelial cells (bMEC). The viability of bMEC was analyzed by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium] assay. Subsequently, bMEC were stimulated with LPS in the presence or absence of morin. Gene expression of proinflammatory cytokines was determined by quantitative real time PCR (qRT-PCR). Nuclear factor-kappaB (NF-kappaB), inhibitory kappa B (IkappaBalpha) protein, extracellular signal-regulated kinase (ERK), p38, and c Jun N-terminal kinase (JNK) were detected by Western blotting. The results showed that cell viability was not affected by morin. Moreover, morin inhibited the gene expression of tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-1beta in LPS stimulated bMEC in a dose-dependent manner. Western blot analysis showed that morin suppressed the phosphorylation of IkappaBalpha, NF-kappaB unit p65, ERK, p38, and JNK in LPS-stimulated bMEC. In conclusion, the protective effects of morin on LPS-induced inflammatory response in bMEC may be due to its ability to suppress NF-kappaB and mitogen-activated protein kinase (MAPK) signaling pathways. These findings suggest that morin may be used as antiinflammatory drug for mastitis. PMID- 26851852 TI - Source of carbohydrate and metabolizable lysine and methionine in the diet of recently weaned dairy calves on digestion and growth. AB - Two 56-d trials with weaned Holstein dairy calves (initially 72 +/- 1.8 kg of body weight, 58 to 60 d of age) fed 95% concentrate and 5% chopped grass hay diets were conducted. Each trial used 96 calves (4 calves/pen). During 15 of the last 21 d of the first trial and 10 of 14 d of the second and third week of the second trial, fecal samples were taken to estimate digestibility using acid insoluble ash as an internal marker. Digestibility estimates along with 56-d average daily gain (ADG), hip width change, body condition score, and fecal score were analyzed with pen as the experimental unit. In trial 1, a textured diet (19% crude protein) with high starch [52% starch, 13% neutral detergent fiber (NDF)] based on whole corn and oats or a pelleted low-starch (20% starch, 35% NDF), high digestible fiber diet were used. Within starch level, diets were formulated from supplemental soybean meal or soybean meal with blood meal and Alimet (Novus International Inc., St. Charles, MO) to provide 2 metabolizable protein levels (1 and 1.07% metabolizable lysine plus methionine). The 4 treatments were analyzed as a completely randomized design with a 2 by 2 factorial arrangement (6 pens/diet). In trial 2, all pelleted diets (19% crude protein) were fed. Diets were based on soybean hulls, wheat middlings, or corn, which contained increasing concentrations of starch (13, 27, and 42% starch and 42, 23, and 16% NDF, respectively; 8 pens/diet). Contrast statements were constructed to separate differences in the means (soybean hulls plus wheat middlings vs. corn; soybean hulls vs. wheat middlings). In trial 1, intake of organic matter (OM) did not differ. Digestibility of OM was greater in calves fed high- versus low starch diets. Digestibility of NDF and starch were less in calves fed the high- versus low-starch diets. Calf ADG and hip width change were greater for high- versus low starch diets. Source of protein did not influence digestibility or ADG. In trial 2, intake of OM was not different. Digestibility of OM was greater in calves fed corn versus other diets. Digestibility of NDF was greater for calves fed soybean hulls versus wheat middlings. Starch digestibility was not different among treatments. Calf ADG and hip width change were greater in calves fed corn versus other diets. High-starch diets were more digestible and supported more growth in 2- to 4-mo-old dairy calves than replacing starch with digestible fiber. Manipulating metabolizable protein compared with a control diet that was predominately corn and soybean meal did not alter growth or digestibility. PMID- 26851853 TI - Milk protein yield and mammary metabolism are affected by phenylalanine deficiency but not by threonine or tryptophan deficiency. AB - Efficient milk protein synthesis requires that the essential AA be presented to the mammary gland in the right amount and proportion to maximize protein synthesis and minimize losses. This study investigated the effects of individual AA deficiencies on cow productivity, mammary metabolism, and glucose whole-body rate of appearance. Five Holstein cows were used in a 5 * 5 Latin square design trial with 10-d periods. Treatments were abomasal infusions of (1) water (CTL); (2) complete AA mixture (TAA); (3) TAA without Phe (No-Phe); (4) TAA without Thr (No-Thr); and (5) TAA without Trp (No-Trp). Each treatment was compared with TAA. Treatment did not affect milk, fat, or lactose yields. Arterial concentrations of Phe, Thr, and Trp decreased with their respective deletions by 60, 76, and 69%. In response to the decreased arterial supply of the deleted AA, mammary plasma flow significantly increased by 55% with No-Thr but did not increase with No-Phe or No-Trp. Mammary uptake of Phe was reduced by No-Phe, accompanied by a reduced milk protein yield; uptakes of Thr and Trp were not affected by their respective deletions, and milk protein yield did not decrease with these treatments. Deletion of Phe tended to reduce its mammary uptake relative to milk output (U:O), accompanied by an increased U:O of Tyr, but deletion of Thr and Trp did not affect the U:O of the corresponding AA. Plasma urea-N concentration was lower with CTL and tended to be higher with No-Phe. Arterial concentrations and mammary uptake of acetate, beta-hydroxybutyrate, glucose, and lactate were unaffected by treatment. Treatment had no effect on glucose rate of appearance at the whole body level. Lactose output as a percentage of glucose whole-body rate of appearance was not affected by treatment. Overall, the study indicated that a deficiency of Phe negatively affected productivity and mammary metabolism but that a deficiency of Thr or Trp did not. PMID- 26851854 TI - Charge properties of peptides derived from casein affect their bioavailability and cytoprotection against H2O2-induced oxidative stress. AB - The effects of charge properties of casein peptides on absorption stability, antioxidant activity, and cytoprotection were evaluated. Alcalase hydrolysates of casein were separated into 4 fractions by cation-exchange chromatography according to charge properties. After simulated digestion and Caco-2 cell transmembrane transport, we determined the total antioxidant capacity (Trolox equivalent antioxidative capacity and oxygen radical antioxidant activity) and nitrogen content of peptide fractions to estimate available antioxidant efficacy and bioavailability (BA) of peptides. Results showed that negatively charged peptide fractions had greater BA and antioxidant activities after digestion and absorption. The peptide permeates were used to test the cytoprotective effect against H2O2-induced oxidative damage in HepG-2 cells. All peptide permeates increased cell viability, elevated catalase activity, and decreased superoxide dismutase activity. However, negatively charged peptide fractions preserved cell viability to a greater degree. Therefore, the negatively charged peptides from casein may be potential antioxidants and could be used as ingredients in functional foods and dietary supplements. PMID- 26851855 TI - Determination of amino acid profile of mare milk produced in the highlands of the Kyrgyz Republic during the milking season. AB - This study was carried out to determine the influence of milking season on amino acid (AA) profile and chemical composition of milk samples from Kyrgyz native breed mares under traditional pasture conditions. Milk samples were collected monthly from May to August 2014 from mares grazing at 2,200 m above sea level. The AA composition was determined by precolumn derivatization with diethyl ethoxymethylenemalonate in HPLC and 18 AA were determined in mare milk. The analytical parameters of linearity (0.01-4 MUg/mL), precision of the method (0.26 4.88% relative standard deviation), derivatization procedure (0.82-2.80% relative standard deviation), and instrument precision (0.08-1.00% relative standard deviation) were determined. The most abundant AA were glutamic acid (0.393-480 g/100g of milk), leucine (0.192-0.230 g/100g of milk), and lysine (0.192-0.230 g/100g of milk). The amount of ornithine was small (0.002-0.015 g/100g of milk). The percentages of essential AA in the protein of mare milk were 46, 46, 51, and 48% for May, June, July, and August, respectively, which demonstrate the high biological value of milk during the whole milking season. PMID- 26851856 TI - Associations between pregnancy-associated glycoproteins and pregnancy outcomes, milk yield, parity, and clinical diseases in high-producing dairy cows. AB - Pregnancy-associated glycoproteins (PAG) are produced by the ruminant placenta and secreted into the maternal circulation throughout pregnancy. The extent to which circulating PAG concentrations predict pregnancy outcomes was examined herein. Also, associations between circulating PAG concentrations and various production parameters and clinical diseases were evaluated. Lactating primiparous and multiparous Holstein cows (n=345) were bred via timed artificial insemination using a standard Ovsynch protocol. Pregnancy was diagnosed by transrectal ultrasonography at d 32, 46, and 74 of gestation. Blood was harvested at d 32 to determine plasma concentrations of PAG and progesterone. Cows pregnant at d 32 that subsequently lost their pregnancy at d 46 and 74 had reduced PAG concentrations. Both artificial insemination service number and parity were associated with plasma PAG concentrations. Concentration of PAG in plasma was greater for cows pregnant from their second or later breeding than those pregnant from the first breeding postpartum, and was increased for primiparous compared with multiparous. In addition, cows with greater milk yield had increased plasma PAG concentrations. No association was detected between body condition score and plasma PAG concentrations. Cows that experienced clinical metritis, metabolic problems, or left displacement abomasum in the early postpartum period preceding breeding had greater plasma PAG concentrations than cows not experiencing these clinical diseases. Also, cows with multiple clinical diseases had increased odds of pregnancy loss when compared with cows not experiencing clinical diseases. Odds ratio testing detected a tendency in the relationship between reduced milk yield and increased pregnancy loss. Collectively, these associations illustrate one feature of the early developing placenta that may predict pregnancy outcomes in dairy cattle. It is unclear if plasma PAG are actively involved with mediating pregnancy outcomes, but modifications in circulating PAG concentrations due to pregnancy loss, milk yield, parity, and clinical disease implicate placental PAG production or PAG release as being responsive to various physiological stimuli. PMID- 26851857 TI - Effect of fermented broth from lactic acid bacteria on pathogenic bacteria proliferation. AB - In this study, the effect that 5 fermented broths of lactic acid bacteria (LAB) strains have on the viability or proliferation and adhesion of 7 potentially pathogenic microorganisms was tested. The fermented broth from Lactococcus lactis C660 had a growth inhibitory effect on Escherichia coli K92 that reached of 31%, 19% to Pseudomonas fluorescens, and 76% to Staphylococcus epidermidis. The growth of Staph. epidermidis was negatively affected to 90% by Lc. lactis 11454 broth, whereas the growth of P. fluorescens (25%) and both species of Staphylococcus (35% to Staphylococcus aureus and 76% to Staph. epidermidis) were inhibited when they were incubated in the presence of Lactobacillus casei 393 broth. Finally, the fermented broth of Lactobacillus rhamnosus showed an inhibitory effect on growth of E. coli K92, Listeria innocua, and Staph. epidermidis reached values of 12, 28, and 76%, respectively. Staphylococcus epidermidis was the most affected strain because the effect was detected from the early stages of growth and it was completely abolished. The results of bacterial adhesion revealed that broths from Lc. lactis strains, Lactobacillus paracasei, and Lb. rhamnosus caused a loss of E. coli K92 adhesion. Bacillus cereus showed a decreased of adhesion in the presence of the broths of Lc. lactis strains and Lb. paracasei. Listeria innocua adhesion inhibition was observed in the presence of Lb. paracasei broth, and the greatest inhibitory effect was registered when this pathogenic bacterium was incubated in presence of Lc. lactis 11454 broth. With respect to the 2 Pseudomonas, we observed a slight adhesion inhibition showed by Lactobacillus rhamnosus broth against Pseudomonas putida. These results confirm that the effect caused by the different LAB assayed is also broth- and species-specific and reveal that the broth from LAB tested can be used as functional bioactive compounds to regulate the adhesion and biofilm synthesis and ultimately lead to preventing food and clinical contamination and colonization of E. coli K92, B. cereus, and Ls. innocua. PMID- 26851858 TI - Thyroid hormone responsive (THRSP) promotes the synthesis of medium-chain fatty acids in goat mammary epithelial cells. AB - In nonruminants, thyroid hormone responsive (THRSP) is a crucial protein for cellular de novo lipogenesis. However, the role of THRSP in regulating the synthesis of milk fatty acid composition in goat mammary gland remains unknown. In the present study, we compared gene expression of THRSP among different goat tissues. Results revealed that THRSP had the highest expression in subcutaneous fat, and expression was higher during lactation compared with the dry period. Overexpression of THRSP upregulated the expression of fatty acid synthase (FASN), stearoyl-coenzyme A desaturase 1 (SCD1), diacylglycerol acyltransferase 2 (DGAT2), and glycerol-3-phosphate acyltransferase (GPAM) in goat mammary epithelial cells. In contrast, overexpression of THRSP led to downregulation of thrombospondin receptor (CD36) and had no effect on the expression of acetyl coenzyme A carboxylase alpha (ACACA) and sterol regulatory element binding transcription factor1 (SREBF1). In addition, overexpressing THRSP in vitro resulted in a significant increase in triacylglycerol (TAG) concentration and the concentrations of C12:0 and C14:0. Taken together, these results highlight an important role of THRSP in regulating lipogenesis in goat mammary epithelial cells. PMID- 26851859 TI - Lactation performance of dairy cows fed yeast-derived microbial protein in low- and high-forage diets. AB - The objective of this study was to investigate the effect of substituting soybean meal products with yeast-derived microbial protein (YMP) on lactation performance in diets containing 2 forage-to-concentrate ratios. Sixteen Holstein cows (4 primiparous and 12 multiparous) were randomly assigned to multiple 4 * 4 Latin squares with a 2 * 2 factorial arrangement of treatments. Diets contained low (LF; 45% of diet DM) or high forage (HF; 65% of diet DM) and YMP at 0 (NYMP) or 2.25% (WYMP) of the diet. The forage mix consisted of 67% corn silage and 33% alfalfa hay on a DM basis. No interactions of forage and YMP were noted for any of the production parameters measured. Feed efficiency (energy-corrected milk/dry matter intake) was greater for cows fed NYMP compared with WYMP. Regardless of the addition of YMP, cows fed LF had greater dry matter intake and produced more milk than cows fed HF. In addition, cows fed LF produced more energy-corrected milk than those fed HF. Milk fat percentage was lower in cows fed LF compared with HF, whereas fat yield was similar between forage concentrations. Fat yield tended to decrease with feeding YMP. Interactions of forage and YMP were observed for propionate concentration, acetate and propionate proportion, and acetate-to propionate ratio. A tendency for an interaction of forage and YMP was also noted for ruminal pH. Cows fed HF diets had greater ruminal ammonia and butyrate concentrations, as well as proportion of butyrate. Arterial concentrations of Ile, Leu, Met, Thr, and Val were greater in cows fed LF. Cows fed NYMP had greater arterial concentrations of Ile, Lys, Trp, and Val than cows fed WYMP. Substitution of soybean proteins with YMP did not improve performance or feed efficiency of high-producing dairy cows regardless of the forage-to-concentrate ratio of the diet. PMID- 26851860 TI - Short communication: Evaluation of sampling socks for detection of Mycobacterium avium ssp. paratuberculosis on dairy farms. AB - Mycobacterium avium ssp. paratuberculosis (MAP) causes Johne's disease, a production-limiting disease in cattle. Detection of infected herds is often done using environmental samples (ES) of manure, which are collected in cattle pens and manure storage areas. Disadvantages of the method are that sample accuracy is affected by cattle housing and type of manure storage area. Furthermore, some sampling locations (e.g., manure lagoons) are frequently not readily accessible. However, sampling socks (SO), as used for Salmonella spp. testing in chicken flocks, might be an easy to use and accurate alternative to ES. The objective of the study was to assess accuracy of SO for detection of MAP in dairy herds. At each of 102 participating herds, 6 ES and 2 SO were collected. In total, 45 herds had only negative samples in both methods and 29 herds had >=1 positive ES and >=1 positive SO. Furthermore, 27 herds with >=1 positive ES had no positive SO, and 1 herd with no positive ES had 1 positive SO. Bayesian simulation with informative priors on sensitivity of ES and MAP herd prevalence provided a posterior sensitivity for SO of 43.5% (95% probability interval=33-58), and 78.5% (95% probability interval=62-93) for ES. Although SO were easy to use, accuracy was lower than for ES. Therefore, with improvements in the sampling protocol (e.g., more SO per farm and more frequent herd visits), as well as improvements in the laboratory protocol, perhaps SO would be a useful alternative for ES. PMID- 26851861 TI - Contrasting effects of progesterone on fertility of dairy and beef cows. AB - The role of progesterone in maintaining pregnancy is well known in the bovine. Subtle differences exist between dairy and beef cows because of differing concentrations of progesterone during recrudescence of postpartum estrous cycles, rate of follicular growth and maturation, proportions of 2- and 3-follicular wave cycles, and other effects on pregnancy outcomes per artificial insemination (P/AI). Because proportions of anovulatory cows before the onset of the artificial insemination (AI) period are greater and more variable in beef (usually ranging from 30 to 70%) than dairy (25%) cows, AI programs were developed to accommodate anovulatory and cycling beef cows enrolled therein. Incorporating a progestin as part of an AI program in beef cows improved P/AI by reducing the proportion of cows having premature luteal regression and short post AI luteal phases. In both genotypes, prolonged dominant follicle growth in a reduced progesterone milieu resulted in increased (1) LH pulses, (2) preovulatory follicle diameter, and (3) concentrations of estradiol and a subsequently larger corpora lutea (CL). In contrast, the progesterone milieu during growth of the ovulatory follicle in an ovulation control program does not seem to affect subsequent P/AI in beef cows, whereas in dairy cows follicle development in an elevated compared with a low progesterone environment increases P/AI. Progesterone status in beef cows at the onset of ovulation synchronization is not related to P/AI in multiparous cows, whereas P/AI was suppressed in primiparous cows that began a timed AI program in a low-progesterone environment. In timed AI programs, elevated concentrations of progesterone just before PGF2alpha and reduced concentrations at AI are critical to maximizing subsequent P/AI in dairy cows, but seemingly much less important in beef cows. By inducing ancillary CL and increasing concentrations of progesterone, human chorionic gonadotropin may increase P/AI when administered to beef cows 7d after AI or at embryo transfer, and its success seems to depend on induction of ancillary CL, whereas in dairy cows increased fertility was detected in cows with multiple CL, human chorionic gonadotropin-enhanced progesterone from original CL, or both. Pregnancy losses after AI are less frequent in beef cows and are not associated with pre-AI progesterone or cycling status, whereas losses in dairy cows are inversely related to progesterone and adversely affected in anovular dairy cows. Genotype and nutritional management likely influence several physiological differences including circulating concentrations of progesterone and responses to supplemental progesterone. PMID- 26851862 TI - Casein infusion rate influences feed intake differently depending on metabolizable protein balance in dairy cows: A multilevel meta-analysis. AB - The effects of casein infusion have been investigated extensively in ruminant species. Its effect on responses in dry matter intake (DMI) has been reviewed and indicated no significant effect. The literature reviewed in the current meta analysis is more extensive and limited to dairy cows fed ad libitum. A total of 51 studies were included in the meta-analysis and data were fitted to a multilevel model adjusting for the correlated nature of some studies. The effect size was the mean difference calculated by subtracting the means for the control from the casein-infused group. Overall, casein infusion [average of 333 g of dry matter (DM)/d; range: 91 to 1,092 g of DM/d] tended to increase responses in DMI by 0.18 kg/d (n=48 studies; 3 outliers). However, an interaction was observed between the casein infusion rate (IR) and the initial metabolizable protein (MP) balance [i.e., supply minus requirements (NRC, 2001)]. When control cows were in negative MP balance (n=27 studies), responses in DMI averaged 0.28 kg/d at mean MP balance (-264 g/d) and casein IR (336 g/d), and a 100g/d increment in the casein IR from its mean increased further responses by 0.14 kg/d (MP balance being constant), compared with cows not infused with casein. In contrast, when control cows were in positive MP balance (n=22 studies; 2 outliers), responses in DMI averaged -0.20 kg/d at mean casein IR (339 g/d), and a 100g/d increment in the casein IR from its mean further decreased responses by 0.33 kg/d, compared with cows not infused with casein. Responses in milk true protein yield at mean casein IR were greater (109 vs. 65 g/d) for cows in negative vs. positive MP balance, respectively, and the influence of the casein IR on responses was significant only for cows in negative MP balance. A 100g/d increment in the casein IR from its mean increased further responses in milk true protein yield by 25 g/d, compared with cows not infused with casein. Responses in blood urea concentration increased in casein studies (+0.59 mM) and the influence of the casein IR was greatest for cows in positive MP balance (0.26 vs. 0.11 mM per 100g/d increment). Responses in DMI were also correlated negatively with responses in blood urea concentration only for cows in positive MP balance. Together, these results suggest an association between satiety and deamination and oxidation of AA supplied in excess of requirements for cows in positive MP balance. Therefore, casein stimulated appetite in cows fed MP-deficient diets possibly via the supply of orexigenic AA or through a pull effect in response to an increased metabolic demand. Conversely, casein induced satiety in cows fed diets supplying MP in excess of requirements. Not precluding other factors involved in satiety (e.g., insulin, gut peptides), casein could have increased the supply of AA (e.g., Ser, Thr, Tyr), which might depress appetite at the brain level or increase the deamination and the oxidation of AA in oversupply in agreement with the hepatic oxidation theory. PMID- 26851863 TI - Cationic P?N interaction in XH3P(+)?NCY complexes (X=H, F, CN, NH2, OH; Y=H, Li, F, Cl) and its cooperativity with hydrogen/lithium/halogen bond. AB - The geometries, interaction energies and bonding properties of cationic pnicogen bond (CPB) interactions are studied in binary XH3P(+)?NCY (X=H, F, CN, NH2, OH; Y=H, Li, F, Cl) complexes by means of MP2/aug-cc-pVTZ calculations. Interaction energies of these binary complexes span a large range, from -16.36kcal/mol in (NH2)H3P(+)?NCF to -71.36kcal/mol in FH3P(+)?NCLi complex. The spin-spin coupling constant across P?N interaction depends considerably on the nature of X and Y substituents. The characteristic of CPB interactions is analyzed in terms of parameters derived from quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses. The charge transfer from the nitrogen base to the cationic acid stabilizes these pnicogen-bonded complexes. For a given XH3P(+), the net charge transfer value increases as the interaction energy of the complex becomes more negative, i.e., NCLi>NCCl>NCH>NCF. Moreover, mutual influence between the CPB and hydrogen/halogen/lithium bond is studied in the ternary XH3P(+)?NCY?NCH complexes. The results indicate that the formation of a Y?N interaction tends to strengthen CPB in the ternary systems. PMID- 26851864 TI - Ion-pi interaction in impacting the nonlinear optical properties of ion-buckybowl complexes. AB - Ion-buckybowl complexes have received considerable attention in modern chemical research due to its fundamental and practical importance. Herein, we performed density functional theory (DFT) to calculate the geometical structure, binding interactions, dipole moments and the first hyperpolarizabilities (betatot) of ion buckybowl complexes (ions are Cl(-) and Na(+), buckybowls are quadrannulene, corannulene and sumanene). It is found that the stabilities of ion-buckybowl compounds primarily originate from the interaction energy, which was proved by a new isomerization energy decomposition analysis approach. Plots of reduced density gradient mirror the ion-pi weak interaction has been formed between the ions and buckybowls. Significantly, the buckybowl subunits cannot effectively impact the nonlinear optical (NLO), but the kind of ion has marked influence on the second-order NLO responses. The betatot values of Cl(-)-buckybowl complexes are all larger as compared to that of Na(+)-buckybowl complexes, which is attributed to the large charge-transfer (CT) from Cl(-) to buckybowl. Our present work will be beneficial for further theoretical and experimental studies on the NLO properties of ion-buckybowl compounds. PMID- 26851865 TI - RADMAP: Simple probes for rapid assessment of complex reactivity: A method and case studies on the reaction of hydrogen atoms with unsaturated organic molecules. AB - RADMAP, an open source program, allows for rapid analysis and visualization of the earliest stages of reactions between any molecule and a monoatomic probe (i.e., H*, H(+), H(-), Br*, or any other monoatomic species) using ab initio methods. This program creates non-planar potential energy surfaces of the initial interaction between a molecule of interest and the monoatomic probe. These surfaces can be used to both predict the site of addition as well as provide a qualitative estimate for the relative proportion of the formation of adducts; therefore, it gives insight into both the reactivity and the kinetic stability of a molecule. The program presents a way to quickly predict the number of signals anticipated in transverse field muon spin resonance spectra as well as their relative intensities. PMID- 26851866 TI - Molecular dynamics simulations of Oxprenolol and Propranolol in a DPPC lipid bilayer. AB - Extensive microscopic molecular dynamics simulations have been performed to study the effects of tow beta-blocker drugs (Propranolol, Oxprenolol) on fully hydrated dipalmitoylphosphatidylcholine (DPPC) in the fluid phase at 323K. Simulation of 4 systems containing varying concentrations of drugs was carried out. For the purpose of comparison, a fully hydrated DPPC bilayer without drugs was also studied at the same level of simulation technique which has been done on 4 other systems. The length of each simulation was 100ns. The effects of concentrations of both drugs were analyzed on lipid bilayer properties, such as electrostatic potential, order parameter, diffusion coefficients, and hydrogen bond formation, etc. Penetration of water in the bilayer system was also investigated using radial distribution function analysis. Efficacy of varying concentrations of both drugs has no significant effect on P-N vector. Consistent with experimental results, by increasing the concentration of Propranolol, the thickness of the bilayer was increased. PMID- 26851867 TI - Insights into the binding interactions of autochthonous dissolved organic matter released from Microcystis aeruginosa with pyrene using spectroscopy. AB - The autochthonous dissolved organic matter (DOM) released by Microcystis aeruginosa (M. aeruginosa-DOM) during its growth period was characterized by spectroscopy. Furthermore, the relationships between the M. aeruginosa-DOM spectroscopic descriptors and the pyrene binding coefficient (KDOC) values were explored. The results showed that the spectroscopic characteristics of the M. aeruginosa-DOM and the binding properties of pyrene were dynamically changed along with the algae growth. Pearson correlation analysis demonstrated that a higher pyrene KDOC value was observed for the M. aeruginosa-DOM that has a higher humification index (HIX) value, a lower biological index (BIX) value and a lower absorption ratio (E2/E3). The presence of protein-like and long-wavelength excited humic-like components may impose negative and positive effects on binding of pyrene by the M. aeruginosa-DOM, respectively. Principal component analysis (PCA) further supported that the binding affinity of pyrene may be primarily influenced by the humification degree of the M. aeruginosa-DOM. PMID- 26851868 TI - The protective service of mangrove ecosystems: A review of valuation methods. AB - Concern over the loss of mangrove ecosystems often focuses on their role in protecting coastal communities from storms that damage property and cause deaths and injury. With climate change, mangrove loss may also result in less protection against coastal storms as well as sea-level rise, saline intrusion and erosion. Past valuations of the storm protection benefit of mangroves have relied on the second-best replacement cost method, such as estimating this protective value with the cost of building human-made storm barriers. More reliable methods instead model the production of the protection service of mangroves and estimate its value in terms of reducing the expected damages or deaths avoided by coastal communities. This paper reviews recent methods of valuing the storm protection service of mangroves and their role in protecting coastal areas and communities of tropical developing countries. PMID- 26851869 TI - Potential effects of sediment contaminants on diatom assemblages in coastal lagoons of New Jersey and New York States. AB - Sediment samples from the coastal lagoons and estuaries of New York and New Jersey were used to investigate the influence of contaminants on diatom assemblages. Multivariate analyses demonstrated correspondence between composition of diatom assemblages and concentrations of several metals and total PAH. The effects of the individual contaminants were difficult to disentangle because of the considerable correlations between their concentrations. The most conspicuous trend was the increase in the relative abundance of small centric planktonic diatoms in response to contamination and the corresponding decrease in the benthic flora. The high relative abundance of planktonic species on contaminated sediments apparently resulted not so much from their tolerance to pollution, but from the paucity of benthic species. A comparison of the assemblages on the surface and at the depth of approximately 8-10cm revealed a statistically significant temporal change in community composition towards planktonic diatoms. PMID- 26851870 TI - Assessment of the zinc diffusion rate in estuarine zones. AB - Industrial pressures suffered by estuarine zones leave a pollution record in their sediment. Thus, high concentrations of many heavy metals and some organic compounds are often found in estuarine sediment. This work aims to contribute to the enhancement of water quality management strategies in these zones by studying in detail the diffusive processes that take place between the water and sediment using a two-pronged approach: experimental practice and numerical simulation. To provide an example of the practical application of the methodologies proposed in this paper, the Suances Estuary (northern Spain) was selected as the study zone. This estuary exhibits significant historical pollution and its sediment acts as a continuous internal source of zinc, mainly due to diffusive processes derived from the concentration gradient between the interstitial water at the solid particles of the sediment and the bottom of the water column. The experimentally obtained results, based on 6 case studies, demonstrated the buffering capacity of the system and allowed the determination of the required time for the mass transfer processes to reach an equilibrium state. Furthermore, the diffusion rate of zinc was approximately modeled taking into consideration the high concentration variability observed in sediment along the entire estuary. The convergence between the modeled and the experimental results indicated the required contact time to reach an equilibrium state in a real field situation. PMID- 26851871 TI - Seasonal variation of methylmercury in sediment cores from the Tagus Estuary (Portugal). AB - Seasonal and spatial variations of dissolved and particulate methylmercury were evaluated for the first time in sediment cores from the Tagus Estuary. Results showed the highest MeHg concentrations in summer months indicating that the "seasonally" methylation process occurs not only at the topmost layers of the sediments but also in the deeper layers of the sediment column. The proportion of MeHg (up to 92%) in some of our pore water samples was higher than values reported in the literature for other estuaries suggesting that the sedimentary environment in the Tagus tends to favour Hg methylation. This work points to the importance of seasonal variation of the MeHg production in sediment cores. In physically dominated estuaries this enhances seasonal MeHg production in deeper sediments that can have serious ecological impacts due to resuspension or advection processes under extreme events by the increase of MeHg transported to the water column. PMID- 26851872 TI - Alteplase vs. urokinase for occluded hemodialysis catheter: A randomized trial. AB - Introduction Thrombosis of tunneled central venous catheters (CVC) in hemodialysis (HD) patients is common and it can lead to the elimination of vascular sites. To compare the efficacy of alteplase vs. urokinase in reestablishing adequate blood flow through completely occluded vascular catheters. Methods In this randomized study, patients with completely occluded tunneled HD catheters received 40 minutes intracatheter dwell with alteplase (1 mg/mL) or urokinase (5000 IU/mL). Primary endpoint was the proportion of patients with occluded catheters achieving post-thrombolytic blood flow of >=250 mL/min. Safety endpoints included the incidence of hemorrhagic and infectious complications. Findings Eligible adult patients (n = 100) were treated with alteplase (n = 44) or urokinase (n = 56). The two groups were similar in gender (male: 51.8% vs. 56.8%, P = 0.35), age (60 +/- 12 vs. 59 +/- 13 years, P = 0.71), time on dialysis (678 +/- 203 vs. 548 +/- 189 days, P = 0.77), diabetes and cardiovascular disease (55.6% vs. 70.4%, P = 0.08 and 17.8% vs. 22.7%, P = 0.38, respectively), jugular vein as main vascular access (54.8% vs. 62.5%, P = 0.57), and time of CVC (278 +/- 63 vs. 218 +/- 59 days, P = 0.67). Primary success with alteplase and urokinase occurred in 42/44 (95%) vs. 46/56 (82%), P = 0.06. Success was not achieved after the second dose of alteplase and urokinase in 1 and 7 cases, respectively (2% vs. 12%, P = 0.075). Serious adverse effects were not observed in both groups. There was no difference between the two groups in infectious complications (P = 0.94). Discussion Alteplase and urokinase are effective thrombolytic agents for restoring HD catheter patency. Our study has revealed a likely slight superiority of alteplase over urokinase for unblocking central lines, but which has enrolled too few patients to be able to detect a difference of this size. PMID- 26851873 TI - Using the evaluation process as a lever for improving health and healthcare accessibility: The case of HCV services organization in Quebec. AB - BACKGROUND: The evaluation process can be a lever to improve pathways of access to healthcare. The objective of this article is to show how an evaluation strategy can both contribute to knowledge development and have direct impacts on health services provision. We use the case of hepatitis C (HCV) services organization to illustrate the use and the value of this evaluative approach. METHOD: Inspired by empowerment evaluation, the transformative-participatory approach involved overlapping phases of knowledge development and discussion with stakeholders. We conducted several knowledge development activities to discern the needs of people with HCV, the resources available, and the facilitators and impediments along the care pathway, starting from prevention and screening, all the way through to treatment. Using an overlapping approach allowed us to regularly transfer acquired knowledge back to the participants in the study settings and also to gather their impressions, interpretations, and suggestions during periods of deliberation. RESULTS: The knowledge development activities made it possible to document the needs, resources, and experiences of people affected by HCV. In the discussion sessions, viable solutions were identified to improve health and healthcare access for people with HCV and to prioritize certain actions. This project demonstrated that using the evaluation process can enable an instrumental, conceptual use of results and, in fact, can have a transformative impact on services organization. PMID- 26851874 TI - Two cases of overlap severe cutaneous adverse reactions to benznidazole treatment for asymptomatic Chagas disease in a nonendemic country. AB - Chagas disease is a parasitosis endemic to South America. It is normally treated with benznidazole as first choice, which has been associated with numerous cutaneous reactions. However, very few benznidazole-associated severe cutaneous adverse reactions have been reported to date. The rise of Chagas disease in nonendemic countries represents a growing public health challenge. We report two patients who met the criteria for drug reaction with eosinophilia and systemic symptoms syndrome and Stevens-Johnson syndrome/toxic epidermal necrolysis according to the RegiSCAR scoring systems. They were thus deemed overlapping cases, with a lymphocyte transformation test positive for benznidazole. Both required intensive care unit admission and both survived. Considering the rising application of this drug for trypanosomiasis in immigrant populations, clinicians should be aware of this newly reported, potentially life-threatening risk. PMID- 26851875 TI - Women leaders in hematology: Inspirations & insights. PMID- 26851876 TI - Effects of Medicaid disease management programs on medical expenditures: Evidence from a natural experiment in Georgia. AB - In recent decades, most states' Medicaid programs have introduced disease management programs for chronically ill beneficiaries. Interventions assist beneficiaries and their health care providers to appropriately manage chronic health condition(s) according to established clinical guidelines. Cost containment has been a key justification for the creation of these programs despite mixed evidence they actually save money. This study evaluates the effects of a disease management program in Georgia by exploiting a natural experiment that delayed the introduction of high-intensity services for several thousand beneficiaries. Expenditures for medical claims decreased an average of $89 per person per month for the high- and moderate-risk groups, but those savings were not large enough to offset the total costs of the program. Impacts varied by the intensity of interventions, over time, and across disease groups. Heterogeneous treatment effect analysis indicates that decreases in medical expenditures were largest at the most expensive tail of the distribution. PMID- 26851877 TI - 7 day services and psychiatry. PMID- 26851878 TI - Chemically and biologically-mediated fertilizing value of manure-derived biochar. AB - This study evaluates the potential of manure-derived biochars in promoting plant growth and enhancing soil chemical and biological properties during a 150day pot experiment. Biochars from pyrolysis of poultry litter (PL) and swine manure (SM) at 400 and 600 degrees C, and a commonly available wood chip (WC) biochar produced at high temperature (1000 degrees C) were incorporated to silt-loam (SL) and sandy (SY) soils on a 2% dry soil weight basis. Ryegrass was sown and moisture was adjusted to 60% water filled pore space (WFPS). The PL400 and SM400 biochars significantly increased (p<0.05) shoot dry matter (DM) yields (SL soil) and enhanced nitrogen (N), phosphorus (P) and potassium (K) uptake by the plants in both soils, compared to the Control. All biochars significantly increased the soil carbon (C) contents compared to the Control. Total N contents were significantly greater for PL400 and PL600 treatments in both soils. The dehydrogenase activity (DA) significantly increased for PL400 and SM400 treatments and was positively correlated with the volatile matter (VM) contents of the biochars, while beta-glucosidase activity (GA) decreased for the same treatments in both soils. All biochars significantly shifted (p<=0.05) the bacterial community structure compared to the Control. This study suggests that pyrolysis of animal manures can produce a biochar that acts as both soil amendment and an organic fertilizer as proven by increased NPK uptake, positive liming effect and high soil nutrient availability, while WC biochar could work only in combination with fertilizers (organic as well as mineral). PMID- 26851879 TI - Zebrafish-based reporter gene assays reveal different estrogenic activities in river waters compared to a conventional human-derived assay. AB - Endocrine disrupting chemicals (EDCs) act on the endocrine system through multiple mechanisms of action, among them interaction with estrogen receptors (ERs) is a well-identified key event in the initiation of adverse outcomes. As the most commonly used estrogen screening assays are either yeast- or human-cell based systems, the question of their (eco)toxicological relevance when assessing risks for aquatic species can be raised. The present study addresses the use of zebrafish (zf) derived reporter gene assays, both in vitro (i.e. zf liver cell lines stably expressing zfERalpha, zfERbeta1 and zfERbeta2 subtypes) and in vivo (i.e. transgenic cyp19a1b-GFP zf embryos), to assess estrogenic contaminants in river waters. By investigating 20 French river sites using passive sampling, high frequencies of in vitro zfER-mediated activities in water extracts were measured. Among the different in vitro assays, zfERbeta2 assay was the most sensitive and responsive one, enabling the detection of active compounds at all investigated sites. In addition, comparison with a conventional human-based in vitro assay highlighted sites that were able to active zfERs but not human ER, suggesting the occurrence of zf-specific ER ligands. Furthermore, a significant in vivo estrogenic activity was detected at the most active sites in vitro, with a good accordance between estradiol equivalent (E2-EQ) concentrations derived from both in vitro and in vivo assays. Overall, this study shows the relevance and usefulness of such novel zebrafish-based assays as screening tools to monitor estrogenic activities in complex mixtures such as water extracts. It also supports their preferred use compared to human-based assays to assess the potential risks caused by endocrine disruptive chemicals for aquatic species such as fish. PMID- 26851880 TI - Influence of quarry mining dust on PM2.5 in a city adjacent to a limestone quarry: Seasonal characteristics and source contributions. AB - To understand the influence of quarry mining dust on particulate matter, ambient PM2.5 and quarry mining dust source samples were collected in a city near quarry facilities during 2013-2014. Samples were subject to chemical analysis for dust related species (Al, Si, Ca, Fe, Ti), tracer metals, carbon components and water soluble ions. Seasonal variations of PM2.5 and its main chemical components were investigated. Distinctive seasonal variations of PM2.5 were observed, with the highest PM2.5 concentrations (112.42MUgm(-3)) in fall and lowest concentrations in summer (45.64MUgm(-3)). For dust-related species, mass fractions of Si and Al did not show obvious seasonal variations, whereas Ca presented higher fractions in spring and summer and lower fractions in fall and winter. A combined receptor model (PMF-CMB) was applied to quantify the quarry mining dust contribution to PM2.5. Seven sources were identified, including quarry mining dust, soil dust, cement dust, coal combustion vehicles, secondary sulfate and secondary nitrate. On a yearly average basis, the contribution of quarry mining dust to PM2.5 was 6%. The contribution of soil dust to PM2.5 was comparable with cement dust (13% and 13%, respectively). Other identified sources included vehicle, secondary sulfate, secondary nitrate and coal combustion, which contributed 23, 15, 9 and 18% of the total mass, respectively. Air mass residence time (AMRT) analysis showed that northeast and southeast regions might be the major PM2.5 source during the sampling campaign. The findings of this study can be used to understand the characteristics of quarry mining dust and control strategies for PM2.5. PMID- 26851881 TI - A closure study of aerosol optical properties at a regional background mountainous site in Eastern China. AB - There is a large uncertainty in evaluating the radiative forcing from aerosol radiation and aerosol-cloud interactions due to the limited knowledge on aerosol properties. In-situ measurements of aerosol physical and chemical properties were carried out in 2012 at Mt. Huang (the Yellow Mountain), a continental background mountainous site in eastern China. An aerosol optical closure study was performed to verify the model outputs by using the measured aerosol optical properties, in which a spherical Mie model with assumptions of external and core-shell mixtures on the basis of a two-component optical aerosol model and high size-segregated element carbon (EC) ratio was applied. Although the spherical Mie model would underestimate the real scattering with increasing particle diameters, excellent agreement between the calculated and measured values was achieved with correlation coefficients above 0.98. Sensitivity experiments showed that the EC ratio had a negligible effect on the calculated scattering coefficient, but largely influenced the calculated absorption coefficient. The high size segregated EC ratio averaged over the study period in the closure was enough to reconstruct the aerosol absorption coefficient in the Mie model, indicating EC size resolution was more important than time resolution in retrieving the absorption coefficient in the model. The uncertainties of calculated scattering and absorption coefficients due to the uncertainties of measurements and model assumptions yielded by a Monte Carlo simulation were +/-6% and +/-14% for external mixture and +/-9% and +/-31% for core-shell mixture, respectively. This study provided an insight into the inherent relationship between aerosol optical properties and physicochemical characteristics in eastern China, which could supplement the database of aerosol optical properties for background sites in eastern China and provide a method for regions with similar climate. PMID- 26851882 TI - Characterization of PM2.5 in Guangzhou, China: uses of organic markers for supporting source apportionment. AB - Organic carbon (OC), elemental carbon (EC), and non-polar organic compounds including n-alkanes (n-C14-n-C40), polycyclic aromatic hydrocarbons (PAHs), phthalate esters (PAEs) and hopanes were quantified in fine particulate (PM2.5), which were collected in urban area of Guangzhou, China in winter and summer in 2012/2013. The pollutants levels were well comparable with the data obtained in previous studies in Pearl River Delta (PRD) region but much lower than most northern Chinese megacities. The contribution of EC to PM2.5 and OC/EC ratio suggest that the pollution sources were relatively consistent in GZ between the two seasons. Benzo[a]pyrene (BaP) was the most abundant PAHs, which were 4.9 and 1.0ng/m(3) on average, accounting for 10.7% and 9.1% to the total quantified PAHs in winter and summer, respectively. The total concentrations of PAEs ranged from 289.1 to 2435ng/m(3) and from 102.4 to 1437ng/m(3), respectively, in winter and summer. Di-n-butyl phthalate (DBP) was the most dominant PAEs. The ambient levels of PAEs could be partly attributed to the widespread uses of the household products, municipal garbage compressing, sewage, and external painting material on the building. Source apportionment for OC with chemical mass balance (CMB) model demonstrated coal combustion, vehicle emission, cooking, and secondary organic compounds (SOC) formation were the four major pollution sources. Both of the indices of n-alkanes and diagnostic PAHs ratios support that anthropogenic sources such as vehicle emission and coal combustion were the significant pollution sources with some extents from epicuticular waxes by terrestrial plants. The ratio of hopanes to EC proved the influences from vehicle emission, and displayed a certain degree of the air aging in the Guangzhou ambient air. PMID- 26851883 TI - From catchment to fish: Impact of anthropogenic pressures on gill histopathology. AB - Gill histopathology was investigated in barbel (Luciobarbus bocagei) and nase (Pseudochondrostoma sp.) in sub-catchments of Paiva River (Portugal) located upstream and downstream of a Waste Water Treatment Plant (WWTP). Multivariate statistical analyses were performed to set up correlations between the species sample (n=24) and injury types (8). The results discriminate well edema and vasodilatation between reference (upstream) and disturbed (downstream) samples. Using a watershed model, time series of physico-chemical parameters and heavy metal concentrations were calibrated and validated for the entire Paiva River basin as to investigate the relationship between water quality and the gill histopathology results. Increased concentrations of heavy metal downstream, specifically of zinc and lead, coincided with a higher severity of histopathological alterations in the fish gills. Significant but less evident relationship between water quality parameters and severity of gill injuries in the analyzed fish species were also observed for fecal coliforms, water temperature and manganese. Notwithstanding the location of the samples upstream and downstream of the WWTP, contamination of Paiva River and its effect on gill injuries cannot be disconnected from other punctual and diffuse pollution sources acting in different sectors within the watershed, namely agriculture and forest management. The severity of histopathological alterations in the fish gills reflected differences in the type and concentration of contaminants in Paiva River, and consequently can be viewed as valuable indicator of water quality. PMID- 26851884 TI - Residential exposure to RF-EMF from mobile phone base stations: Model predictions versus personal and home measurements. AB - INTRODUCTION: Geospatial models have been demonstrated to reliably and efficiently estimate RF-EMF exposure from mobile phone base stations (downlink) at stationary locations with the implicit assumption that this reflects personal exposure. In this study we evaluated whether RF-EMF model predictions at the home address are a good proxy of personal 48h exposure. We furthermore studied potential modification of this association by degree of urbanisation. METHOD: We first used an initial NISMap estimation (at an assumed height of 4.5m) for 9563 randomly selected addresses in order to oversample addresses with higher exposure levels and achieve exposure contrast. We included 47 individuals across the range of potential RF-EMF exposure and used NISMap to re-assess downlink exposure at the home address (at bedroom height). We computed several indicators to determine the accuracy of the NISMap model predictions. We compared residential RF-EMF model predictions with personal 48h, at home, and night-time (0:00-8:00AM) ExpoM3 measurements, and with EME-SPY 140 spot measurements in the bedroom. We obtained information about urbanisation degree and compared the accuracy of model predictions in high and low urbanised areas. RESULTS: We found a moderate Spearman correlation between model predictions and personal 48h (rSp=0.47), at home (rSp=0.49), at night (rSp=0.51) and spot measurements (rSp=0.54). We found no clear differences between high and low urbanised areas (48h: high rSp=0.38, low rSp=0.55, bedroom spot measurements: high rSp=0.55, low rSp=0.50). DISCUSSION: We achieved a meaningful ranking of personal downlink exposure irrespective of degree of urbanisation, indicating that these models can provide a good proxy of personal exposure in areas with varying build-up. PMID- 26851885 TI - Effects of Shen-Fu injection on coagulation-fibrinolysis disorders in a porcine model of cardiac arrest. AB - OBJECTIVE: The objective of the study is to investigate the effects of Shen-Fu injection (SFI) on coagulation-fibrinolysis disorders in a porcine model of cardiac arrest. MATERIALS AND METHODS: Thirty Wuzhishan pigs were randomly assigned into the sham operation group (SO group, n = 6), epinephrine group (EP group, n = 12), and SFI group (n = 12). After 8 minutes of untreated ventricular fibrillation (VF), pigs in the EP group or SFI group were administered with either EP (0.02 mg/kg) or SFI (1.0 mL/kg), respectively. Plasma levels of tissue factor, thrombin-antithrombin complex, tissue factor pathway inhibitor, antithrombin III, protein C, tissue plasminogen activator, plasminogen activator inhibitor 1, soluble thrombomodulin, and soluble endothelial protein C receptor were measured at baseline, 1, 6, 12, and 24 hours after return of spontaneous circulation (ROSC). In addition, arterial lactate levels were measured at baseline, 1, 6, 12, and 24 hours after ROSC, and lactate clearance was calculated at 1, 6, 12, and 24 hours after ROSC. RESULTS: Compared with the EP group, tissue factor, thrombin-antithrombin complex, tissue factor pathway inhibitor, tissue plasminogen activator, and plasminogen activator inhibitor 1 levels were significantly lower, whereas antithrombin III and protein C levels were significantly higher in the SFI group (all P < .05). In addition, soluble thrombomodulin and soluble endothelial protein C receptor levels in the SFI group were significantly lower in comparison to the EP group (all P < .01). Furthermore, arterial lactate levels were significantly lower, and lactate clearance was higher in the SFI group (all P < .01). CONCLUSIONS: This study demonstrates that SFI can inhibit coagulation-fibrinolysis disorders after cardiac arrest, which may be associated with alleviating endothelial damage and improving systemic metabolism. PMID- 26851886 TI - Icare vs Tono-Pen in the ED. PMID- 26851887 TI - Vermicompost humic acids modulate the accumulation and metabolism of ROS in rice plants. AB - This work aims to determine the reactive oxygen species (ROS) accumulation, gene expression, anti-oxidant enzyme activity, and derived effects on membrane lipid peroxidation and certain stress markers (proline and malondialdehyde-MDA) in the roots of unstressed and PEG-stressed rice plants associated with vermicompost humic acid (VCHA) application. The results show that the application of VCHA to the roots of unstressed rice plants caused a slight but significant increase in root ROS accumulation and the gene expression and activity of the major anti oxidant enzymes (superoxide dismutase and peroxidase). This action did not have negative effects on root development, and an increase in both root growth and root proliferation occurred. However, the root proline and MDA concentrations and the root permeability results indicate the development of a type of mild stress associated with VCHA application. When VCHA was applied to PEG-stressed plants, a clear alleviation of the inhibition in root development linked to PEG-mediated osmotic stress was observed. This was associated with a reduction in root ROS production and anti-oxidant enzymatic activity caused by osmotic stress. This alleviation of stress caused by VCHA was also reflected as a reduction in the PEG mediated concentration of MDA in the root as well as root permeability. In summary, the beneficial action of VCHA on the root development of unstressed or PEG-stressed rice plants clearly involves the modulation of ROS accumulation in roots. PMID- 26851888 TI - Identification of genes coding for functional zeaxanthin epoxidases in the diatom Phaeodactylum tricornutum. AB - Phaeodactylum tricornutum like other diatoms synthesizes fucoxanthin and diadinoxanthin as major carotenoid end products. The genes involved have recently been assigned for early pathway steps. Beyond beta-carotene, only gene candidates for beta-carotene hydroxylase, zeaxanthin epoxidase and zeaxanthin de-epoxidase have been proposed from the available genome sequence. The two latter enzymes may be involved in the two different xanthophyll cycles which operate in P. tricornutum. The function of three putative zeaxanthin epoxidase genes (zep) was addressed by pathway complementation in the Arabidopsis thaliana Zep mutant npq2. Genes zep2 and zep3 were able to restore zeaxanthin epoxidation and a functional xanthophyll cycle but the corresponding enzymes exhibited different catalytic activities. Zep3 functioned as a zeaxanthin epoxidase whereas Zep2 exhibited a broader substrate specificity additionally converting lutein to lutein-5,6 epoxide. Although zep1 was transcribed and the protein could be identified after import into the chloroplast in A. thaliana, Zep1 was found not to be functional in zeaxanthin epoxidation. The non-photochemical quenching kinetics of wild type A. thaliana was only restored in transformant npq2-zep3. PMID- 26851889 TI - Genomes of Strongylocentrotus franciscanus and Lytechinus variegatus: are there any genomic explanations for the two order of magnitude difference in the lifespan of sea urchins? AB - Sea urchins are marine invertebrates of extreme diversity of life span. Red sea urchin S. franciscanus is among the longest living creatures of the Ocean. Its lifetime is estimated to exceed a century, while the green sea urchin L. variegatus hardly survives more than four years. We sequenced and compared the genomes of these animals aiming at determination of the genetic basis of their longevity difference. List of genes related to the longevity of other animal species was created and used for homology search among the genomic data obtained in this study. Amino acid sequences of longevity related proteins of S. fransciscanus and L. variegatus as well as from a set of model species, were aligned and grouped on the basis of the species lifespan. Amino acid residues specific for a longevity group were identified. Proteins containing amino acids whose identity correlated with the lifespan were clustered on the basis of their function. PMID- 26851890 TI - Evaluating a handbook for parents of children with food allergy: a randomized clinical trial. AB - BACKGROUND: Educational materials are needed to support parent management of and coping with childhood food allergy. OBJECTIVES: To evaluate whether a food allergy handbook can improve parental knowledge, confidence, and quality of life associated with the management of food allergy. METHODS: Participants included 153 parents of children diagnosed as having food allergy within the past 12 months who were recruited from hospital-based allergy clinics and food allergy organizations. Parents were randomly assigned to receive the food allergy handbook either after a baseline survey (handbook group) or at the conclusion of study participation (control group). Outcomes were assessed using online surveys at baseline, 2-week follow-up, and 2-month follow-up. RESULTS: Compared with parents in the control group, parents in the handbook group had significantly greater improvement in knowledge at the 2-week (mean difference, 2.92; 95% confidence interval [CI], 2.20-3.64; P < .001) and 2-month (mean difference, 2.46; 95% CI, 1.68-3.25; P < .001) follow-ups, significantly greater improvement in confidence at the 2-week (mean difference, 0.24; 95% CI, 0.09-0.39; P = .002) and 2-month (mean difference, 0.47; 95% CI, 0.30-0.63; P < .001) follow-ups, and significantly greater improvement in quality of life at the 2-month follow-up (mean difference, -0.48; 95% CI, -0.79 to -0.16; P = .004). Parents reported satisfaction with the content the handbook, with mean ratings of individual sections ranging from 2.7 to 3.2 on a 0- to 4-point scale and modal ratings of 3 (very useful). CONCLUSIONS: The food allergy handbook evaluated in this study is an effective parent resource to supplement physician management of food allergy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01914978. PMID- 26851891 TI - Novel Protein Arginine Methyltransferase 8 Isoform Is Essential for Cell Proliferation. AB - Identification of molecular mechanisms that regulate cellular replicative lifespan is needed to better understand the transition between a normal and a neoplastic cell phenotype. We have previously reported that low oxygen-mediated activity of FGF2 leads to an increase in cellular lifespan and acquisition of regeneration competence in human dermal fibroblasts (iRC cells). Though cells display a more plastic developmental phenotype, they remain non-tumorigenic when injected into SCID mice (Page et al. [2009] Cloning Stem Cells 11:417-426; Page et al. [2011] Eng Part A 17:2629-2640) allowing for investigation of mechanisms that regulate increased cellular lifespan in a non-tumorigenic system. Analysis of chromatin modification enzymes by qRT-PCR revealed a 13.3-fold upregulation of the arginine methyltransferase PRMT8 in iRC cells. Increased protein expression was confirmed in both iRC and human embryonic stem cells-the first demonstration of endogenous human PRMT8 expression outside the brain. Furthermore, iRC cells express a novel PRMT8 mRNA variant. Using siRNA-mediated knockdown we demonstrated that this novel variant was required for proliferation of human dermal fibroblasts (hDFs) and grade IV glioblastomas. PRMT8 upregulation in a non tumorigenic system may offer a potential diagnostic biomarker and a therapeutic target for cells in pre-cancerous and cancerous states. J. Cell. Biochem. 117: 2056-2066, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26851893 TI - Effect of fermentation parameters, elicitors and precursors on camptothecin production from the endophyte Fusarium solani. AB - Volumetric productivity of camptothecin from the suspension culture of the endophyte Fusarium solani was enhanced up to ~152 fold (from 0.19 MUg l(-1) d(-1) to 28.9 MUg l(-1) d(-1)) under optimized fermentation conditions including initial pH (6.0), temperature (32 degrees C) and agitation speed (80 rpm) with (5% (v/v)) ethanol as medium component. Among various elicitors and precursors studied, tryptamine (0.5 mM) as precursor and bovine serum albumin (BSA) (0.075 mM) as an elicitor added on day 6 of the cultivation period resulted in maximum enhancement of camptothecin concentration (up to 4.5 and 3.4-fold, respectively). These leads provide immense scope for further enhancement in camptothecin productivity at bioreactor level. The cytotoxicity analysis of the crude camptothecin extract from the fungal biomass revealed its high effectiveness against colon and mammary gland cancer cell lines. PMID- 26851892 TI - Epidemiology of myasthenia gravis in Northern Portugal: Frequency estimates and clinical epidemiological distribution of cases. AB - INTRODUCTION: In this study we estimated the prevalence, incidence, and mortality of myasthenia gravis (MG) in northern Portugal and characterized the clinical features of the patients identified. METHODS: We used 2 data sources: clinical records from the hospitals and pyridostigmine prescription registers. RESULTS: On December 31, 2013, we estimated a point prevalence of 111.7 patients per million population. The highest prevalence was observed in the group >65 years of age, especially in men (288.1 per million). During 2013, we estimated an incidence rate of 6.3 per million per year. Among women, the incidence rate was highest in the 15-49-year age group; in men, incidence increased with age up to 22.1 per million in those >65 years old. The MG-related mortality rate was 0.5 per million. CONCLUSIONS: These figures are in keeping with similar studies and emphasize the importance of diagnosis and management of MG in elderly populations. Muscle Nerve 54: 413-421, 2016. PMID- 26851894 TI - Universal model of slow pyrolysis technology producing biochar and heat from standard biomass needed for the techno-economic assessment. AB - Biochar as a soil amendment and carbon sink becomes in last period one of the vast, interesting product of slow pyrolysis. Simplest and most used industrial process arrangement is a production of biochar and heat at the same time. Proposed mass and heat balance model consist of heat consumers (heat demand side) and heat generation-supply side. Direct burning of all generated uncondensed volatiles from biomass provides heat. Calculation of the mass and heat balance of both sides reveals the internal distribution of masses and energy inside process streams and units. Thermodynamic calculations verified not only the concept but also numerical range of the results. The comparisons with recent published scientific and vendors data prove its general applicability and reliability. The model opens the possibility for process efficiency innovations. Finally, the model was adapted to give more investors favorable results and support techno economic assessments entirely. PMID- 26851895 TI - Identification of recalcitrant compounds in a pilot-scale AB system: An adsorption (A) stage followed by a biological (B) stage to treat municipal wastewater. AB - This manuscript presents a comparison of the A-stage and B-stage sludges in terms of anaerobic biodegradability and low molecular weight compounds present in the supernatant using Gas Chromatography-Mass Spectrometry (GC-MS). The GC-MS analysis of A-stage and B-stage supernatants identified respectively 43 and 19 organic compounds consisting mainly of aromatics (27.9% and 21%), alcohols (25.6% and 15%) and acids (30.2% and 15%). The methane potential was found to be 349+/-1 mL CH4/g VS and 238+/-12 mL CH4/g VS, respectively. After anaerobic digestion of these sludges, a greater proportion of aromatics (42% and 58%) and a lower proportion of acids (10% and 10%) and alcohols (16% and 10%) was observed. PMID- 26851896 TI - The effect of oxalic and itaconic acids on threo-Ds-isocitric acid production from rapeseed oil by Yarrowia lipolytica. AB - The effect of oxalic and itaconic acids, the inhibitors of the isocitrate lyase, on the production of isocitric acid by the wild strain Yarrowia lipolytica VKM Y 2373 grown in the medium containing rapeseed oil was studied. In the presence of oxalic and itaconic acids, strain Y. lipolytica accumulated in the medium isocitric acid (70.0 and 82.7 g/L, respectively) and citric acid (23.0 and 18.4 g/L, respectively). In control experiment, when the inhibitors were not added to the medium, the strain accumulated isocitric and citric acids at concentrations of 62.0 and 28.0 g/L, respectively. Thus, the use of the oxalic and itaconic acids as additives to the medium is a simple and convenient method of isocitric acid production with a minimum content of citric acid. PMID- 26851898 TI - Culture strategies for lipid production using acetic acid as sole carbon source by Rhodosporidium toruloides. AB - Rhodosporidium toruloides AS 2.1389 was tested using different concentrations of acetic acid as a low-cost carbon source for the production of microbial lipids, which are good raw materials for biodiesel production. It grew and had higher lipid contents in media containing 4-20 g/L acetic acid as the sole carbon source, compared with that in glucose-containing media under the same culture conditions. At acetic acid concentrations as high as 20 g/L and the optimal carbon-to-nitrogen ratio (C/N) of 200 in a batch culture, the highest biomass production was 4.35 g/L, with a lipid content of 48.2%. At acetic acid concentrations as low as 4 g/L, a sequencing batch culture (SBC) with a C/N of 100 increased biomass production to 4.21 g/L, with a lipid content of 38.6%. These results provide usable culture strategies for lipid production by R. toruloides AS 2.1389 when using diverse waste-derived volatile fatty acids. PMID- 26851897 TI - Enhanced dewaterability of waste activated sludge by Fe(II)-activated peroxymonosulfate oxidation. AB - The effect of Fe(II)-activated peroxymonosulfate (Fe(II)-PMS) oxidation on the waste activated sludge (WAS) dewatering and its mechanisms were investigated in this study. The capillary suction time (CST), specific resistance to filterability (SRF) of sludge and water content (WC) of dewatered sludge cake were chosen as the main parameters to evaluate the sludge dewaterability. Experimental results showed that Fe(II)-PMS effectively disintegrated sludge and improved sludge dewaterability. High CST and SRF reduction (90% and 97%) was achieved at the optimal conditions of PMS (HSO5(-)) 0.9 mmol/gVSS, Fe(II) 0.81 mmol/gVSS, and pH 6.8. Extracellular polymeric substances (EPS) and three dimensional excitation-emission matrix (3D-EEM) fluorescence spectroscopy before and after Fe(II)-PMS oxidation were determined to explain the enhanced dewatering mechanism. The release of EPS-bound water induced by the destruction of EPS was the primary reason for the improvement of sludge dewaterability during Fe(II)-PMS oxidation. PMID- 26851899 TI - Ionic liquid as a promising biobased green solvent in combination with microwave irradiation for direct biodiesel production. AB - The wet biomass microalgae of Nannochloropsis sp. was converted to biodiesel using direct transesterification (DT) by microwave technique and ionic liquid (IL) as the green solvent. Three different ionic liquids; 1-butyl-3 metyhlimidazolium chloride ([BMIM][Cl], 1-ethyl-3-methylimmidazolium methyl sulphate [EMIM][MeSO4] and 1-butyl-3-methylimidazolium trifluoromethane sulfonate [BMIM][CF3SO3]) and organic solvents (hexane and methanol) were used as co solvents under microwave irradiation and their performances in terms of percentage disruption, cell walls ruptured and biodiesel yields were compared at different reaction times (5, 10 and 15 min). [EMIM][MeSO4] showed highest percentage cell disruption (99.73%) and biodiesel yield (36.79% per dried biomass) after 15 min of simultaneous reaction. The results demonstrated that simultaneous extraction-transesterification using ILs and microwave irradiation is a potential alternative method for biodiesel production. PMID- 26851900 TI - Communication: Librational dynamics in water, sI and sII clathrate hydrates, and ice Ih: Molecular-dynamics insights. AB - Equilibrium molecular-dynamics simulations have been performed for liquid water, and on metastable sI and sII polymorphs of empty hydrate lattices, in addition to ice Ih, in order to study the dynamical properties of librational motion (rotation oscillation) depicted by protons in water molecules. In particular, hydrate lattices were found to display prominent "bifurcated" features, or peaks, at circa 70 and 80-95 meV (or ~560 and 640-760 cm(-1), respectively), also displayed by ice, in essentially quantitative agreement with experimental neutron scattering data. However, observed differences in dispersion between these librational modes between these two structures (both hydrate polymorphs vis-a-vis ice), owing primarily to density effects, have been decomposed into contributions arising from angular-velocity dynamics about axes in the local molecular frame of water molecules, with in-plane "wagging" and "twisting" rationalising one mode at ~70 meV, and out-of-plane motion for the higher-frequency band. This was confirmed explicitly by a type of de facto normal-mode analysis, in which only immediate layers of water molecules about the one under consideration were allowed to move. In contrast, liquid water displayed no marked preference for such local in- or out-of-plane modes characterising librational motion, owing to the marked absence of rigid, pentamers or hexamers therein. PMID- 26851901 TI - Communication: Consistent interpretation of molecular simulation kinetics using Markov state models biased with external information. AB - Molecular simulations can provide microscopic insight into the physical and chemical driving forces of complex molecular processes. Despite continued advancement of simulation methodology, model errors may lead to inconsistencies between simulated and reference (e.g., from experiments or higher-level simulations) observables. To bound the microscopic information generated by computer simulations within reference measurements, we propose a method that reweights the microscopic transitions of the system to improve consistency with a set of coarse kinetic observables. The method employs the well-developed Markov state modeling framework to efficiently link microscopic dynamics with long-time scale constraints, thereby consistently addressing a wide range of time scales. To emphasize the robustness of the method, we consider two distinct coarse grained models with significant kinetic inconsistencies. When applied to the simulated conformational dynamics of small peptides, the reweighting procedure systematically improves the time scale separation of the slowest processes. Additionally, constraining the forward and backward rates between metastable states leads to slight improvement of their relative stabilities and, thus, refined equilibrium properties of the resulting model. Finally, we find that difficulties in simultaneously describing both the simulated data and the provided constraints can help identify specific limitations of the underlying simulation approach. PMID- 26851902 TI - A new discretization for the polarizable continuum model within the domain decomposition paradigm. AB - We present a new algorithm to solve the polarizable continuum model equation in a framework compatible with the strategy previously developed by us for the conductor-like screening model based on Schwarz's domain decomposition method (ddCOSMO). The new discretization is systematically improvable and is fully consistent with ddCOSMO so that it reproduces ddCOSMO results for large dielectric constants. PMID- 26851903 TI - Efficient linear-scaling second-order Moller-Plesset perturbation theory: The divide-expand-consolidate RI-MP2 model. AB - The Resolution of the Identity second-order Moller-Plesset perturbation theory (RI-MP2) method is implemented within the linear-scaling Divide-Expand Consolidate (DEC) framework. In a DEC calculation, the full molecular correlated calculation is replaced by a set of independent fragment calculations each using a subset of the total orbital space. The number of independent fragment calculations scales linearly with the system size, rendering the method linear scaling and massively parallel. The DEC-RI-MP2 method can be viewed as an approximation to the DEC-MP2 method where the RI approximation is utilized in each fragment calculation. The individual fragment calculations scale with the fifth power of the fragment size for both methods. However, the DEC-RI-MP2 method has a reduced prefactor compared to DEC-MP2 and is well-suited for implementation on massively parallel supercomputers, as demonstrated by test calculations on a set of medium-sized molecules. The DEC error control ensures that the standard RI MP2 energy can be obtained to the predefined precision. The errors associated with the RI and DEC approximations are compared, and it is shown that the DEC-RI MP2 method can be applied to systems far beyond the ones that can be treated with a conventional RI-MP2 implementation. PMID- 26851904 TI - Critical analysis of fragment-orbital DFT schemes for the calculation of electronic coupling values. AB - We present a critical analysis of the popular fragment-orbital density-functional theory (FO-DFT) scheme for the calculation of electronic coupling values. We discuss the characteristics of different possible formulations or "flavors" of the scheme which differ by the number of electrons in the calculation of the fragments and the construction of the Hamiltonian. In addition to two previously described variants based on neutral fragments, we present a third version taking a different route to the approximate diabatic state by explicitly considering charged fragments. In applying these FO-DFT flavors to the two molecular test sets HAB7 (electron transfer) and HAB11 (hole transfer), we find that our new scheme gives improved electronic couplings for HAB7 (-6.2% decrease in mean relative signed error) and greatly improved electronic couplings for HAB11 ( 15.3% decrease in mean relative signed error). A systematic investigation of the influence of exact exchange on the electronic coupling values shows that the use of hybrid functionals in FO-DFT calculations improves the electronic couplings, giving values close to or even better than more sophisticated constrained DFT calculations. Comparing the accuracy and computational cost of each variant, we devise simple rules to choose the best possible flavor depending on the task. For accuracy, our new scheme with charged-fragment calculations performs best, while numerically more efficient at reasonable accuracy is the variant with neutral fragments. PMID- 26851905 TI - Time-dependent wave packet averaged vibrational frequencies from femtosecond stimulated Raman spectra. AB - Femtosecond stimulated Raman spectroscopy (FSRS) on the Stokes side arises from a third order polarization, P(3)(t), which is given by an overlap of a first order wave packet, |Psi2(1)(pu,t)>, prepared by a narrow band (ps) Raman pump pulse, Epu(t), on the upper electronic e2 potential energy surface (PES), with a second order wave packet, resembles the zeroth order wave packet |Psi1(0)(t)> on the lower PES spatially, but with a force on |Psi2(1)(pu,t)> along the coordinates of the reporter modes due to displacements in the equilibrium position, so that . The observable FSRS Raman gain is related to the imaginary part of P(3)(omega). The imaginary and real parts of P(3)(omega) are related by the Kramers-Kronig relation. Hence, from the FSRS Raman gain, we can obtain the complex P(3)(omega), whose Fourier transform then gives us the complex P(3)(t) to analyze for omegaj(t). We apply the theory, first, to a two dimensional model system with one conformational mode of low frequency and one reporter vibrational mode of higher frequency with good results, and then we apply it to the time-resolved FSRS spectra of the cis-trans isomerization of retinal in rhodopsin [P. Kukura et al., Science 310, 1006 (2005)]. We obtain the vibrational frequency up-shift time constants for the C12-H wagging mode at 216 fs and for the C10-H wagging mode at 161 fs which are larger than for the C11-H wagging mode at 127 fs, i.e., the C11-H wagging mode arrives at its final frequency while the C12-H and C10-H wagging modes are still up-shifting to their final values, agreeing with the findings of Yan et al. [Biochemistry 43, 10867 (2004)]. PMID- 26851906 TI - Variational tensor approach for approximating the rare-event kinetics of macromolecular systems. AB - Essential information about the stationary and slow kinetic properties of macromolecules is contained in the eigenvalues and eigenfunctions of the dynamical operator of the molecular dynamics. A recent variational formulation allows to optimally approximate these eigenvalues and eigenfunctions when a basis set for the eigenfunctions is provided. In this study, we propose that a suitable choice of basis functions is given by products of one-coordinate basis functions, which describe changes along internal molecular coordinates, such as dihedral angles or distances. A sparse tensor product approach is employed in order to avoid a combinatorial explosion of products, i.e., of the basis set size. Our results suggest that the high-dimensional eigenfunctions can be well approximated with relatively small basis set sizes. PMID- 26851907 TI - Self-consistent second-order Green's function perturbation theory for periodic systems. AB - Despite recent advances, systematic quantitative treatment of the electron correlation problem in extended systems remains a formidable task. Systematically improvable Green's function methods capable of quantitatively describing weak and at least qualitatively strong correlations appear as promising candidates for computational treatment of periodic systems. We present a periodic implementation of temperature-dependent self-consistent 2nd-order Green's function (GF2) method, where the self-energy is evaluated in the basis of atomic orbitals. Evaluating the real-space self-energy in atomic orbitals and solving the Dyson equation in k space are the key components of a computationally feasible algorithm. We apply this technique to the one-dimensional hydrogen lattice--a prototypical crystalline system with a realistic Hamiltonian. By analyzing the behavior of the spectral functions, natural occupations, and self-energies, we claim that GF2 is able to recover metallic, band insulating, and at least qualitatively Mott regimes. We observe that the iterative nature of GF2 is essential to the emergence of the metallic and Mott phases. PMID- 26851908 TI - Phase space barriers and dividing surfaces in the absence of critical points of the potential energy: Application to roaming in ozone. AB - We examine the phase space structures that govern reaction dynamics in the absence of critical points on the potential energy surface. We show that in the vicinity of hyperbolic invariant tori, it is possible to define phase space dividing surfaces that are analogous to the dividing surfaces governing transition from reactants to products near a critical point of the potential energy surface. We investigate the problem of capture of an atom by a diatomic molecule and show that a normally hyperbolic invariant manifold exists at large atom-diatom distances, away from any critical points on the potential. This normally hyperbolic invariant manifold is the anchor for the construction of a dividing surface in phase space, which defines the outer or loose transition state governing capture dynamics. We present an algorithm for sampling an approximate capture dividing surface, and apply our methods to the recombination of the ozone molecule. We treat both 2 and 3 degrees of freedom models with zero total angular momentum. We have located the normally hyperbolic invariant manifold from which the orbiting (outer) transition state is constructed. This forms the basis for our analysis of trajectories for ozone in general, but with particular emphasis on the roaming trajectories. PMID- 26851909 TI - Natural occupation numbers in two-electron quantum rings. AB - Natural orbitals (NOs) are central constituents for evaluating correlation energies through efficient approximations. Here, we report the closed-form expression of the NOs of two-electron quantum rings, which are prototypical finite-extension systems and new starting points for the development of exchange correlation functionals in density functional theory. We also show that the natural occupation numbers for these two-electron paradigms are in general non vanishing and follow the same power law decay as atomic and molecular two electron systems. PMID- 26851910 TI - Energy landscapes and persistent minima. AB - We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests. PMID- 26851911 TI - A simple quasi-diabatization scheme suitable for spectroscopic problems based on one-electron properties of interacting states. AB - We present a simple quasi-diabatization scheme applicable to spectroscopic studies that can be applied using any wavefunction for which one-electron properties and transition properties can be calculated. The method is based on rotation of a pair (or set) of adiabatic states to minimize the difference between the given transition property at a reference geometry of high symmetry (where the quasi-diabatic states and adiabatic states coincide) and points of lower symmetry where quasi-diabatic quantities are desired. Compared to other quasi-diabatization techniques, the method requires no special coding, facilitates direct comparison between quasi-diabatic quantities calculated using different types of wavefunctions, and is free of any selection of configurations in the definition of the quasi-diabatic states. On the other hand, the method appears to be sensitive to multi-state issues, unlike recent methods we have developed that use a configurational definition of quasi-diabatic states. Results are presented and compared with two other recently developed quasi-diabatization techniques. PMID- 26851912 TI - Accurate molecular dynamics and nuclear quantum effects at low cost by multiple steps in real and imaginary time: Using density functional theory to accelerate wavefunction methods. AB - The development and implementation of increasingly accurate methods for electronic structure calculations mean that, for many atomistic simulation problems, treating light nuclei as classical particles is now one of the most serious approximations. Even though recent developments have significantly reduced the overhead for modeling the quantum nature of the nuclei, the cost is still prohibitive when combined with advanced electronic structure methods. Here we present how multiple time step integrators can be combined with ring-polymer contraction techniques (effectively, multiple time stepping in imaginary time) to reduce virtually to zero the overhead of modelling nuclear quantum effects, while describing inter-atomic forces at high levels of electronic structure theory. This is demonstrated for a combination of MP2 and semi-local DFT applied to the Zundel cation. The approach can be seamlessly combined with other methods to reduce the computational cost of path integral calculations, such as high-order factorizations of the Boltzmann operator or generalized Langevin equation thermostats. PMID- 26851913 TI - Ab initio molecular dynamics with nuclear quantum effects at classical cost: Ring polymer contraction for density functional theory. AB - Path integral molecular dynamics simulations, combined with an ab initio evaluation of interactions using electronic structure theory, incorporate the quantum mechanical nature of both the electrons and nuclei, which are essential to accurately describe systems containing light nuclei. However, path integral simulations have traditionally required a computational cost around two orders of magnitude greater than treating the nuclei classically, making them prohibitively costly for most applications. Here we show that the cost of path integral simulations can be dramatically reduced by extending our ring polymer contraction approach to ab initio molecular dynamics simulations. By using density functional tight binding as a reference system, we show that our ring polymer contraction scheme gives rapid and systematic convergence to the full path integral density functional theory result. We demonstrate the efficiency of this approach in ab initio simulations of liquid water and the reactive protonated and deprotonated water dimer systems. We find that the vast majority of the nuclear quantum effects are accurately captured using contraction to just the ring polymer centroid, which requires the same number of density functional theory calculations as a classical simulation. Combined with a multiple time step scheme using the same reference system, which allows the time step to be increased, this approach is as fast as a typical classical ab initio molecular dynamics simulation and 35* faster than a full path integral calculation, while still exactly including the quantum sampling of nuclei. This development thus offers a route to routinely include nuclear quantum effects in ab initio molecular dynamics simulations at negligible computational cost. PMID- 26851914 TI - Characterizing metastable states beyond energies and lifetimes: Dyson orbitals and transition dipole moments. AB - The theoretical description of electronic resonances is extended beyond calculations of energies and lifetimes. We present the formalism for calculating Dyson orbitals and transition dipole moments within the equation-of-motion coupled-cluster singles and doubles method for electron-attached states augmented by a complex absorbing potential (CAP-EOM-EA-CCSD). The capabilities of the new methodology are illustrated by calculations of Dyson orbitals of various transient anions. We also present calculations of transition dipole moments between transient and stable anionic states as well as between different transient states. Dyson orbitals characterize the differences between the initial neutral and final electron-attached states without invoking the mean-field approximation. By extending the molecular-orbital description to correlated many electron wave functions, they deliver qualitative insights into the character of resonance states. Dyson orbitals and transition moments are also needed for calculating experimental observables such as spectra and cross sections. Physically meaningful results for those quantities are obtained only in the framework of non-Hermitian quantum mechanics, e.g., in the presence of a complex absorbing potential (CAP), when studying resonances. We investigate the dependence of Dyson orbitals and transition moments on the CAP strength and illustrate how Dyson orbitals help understand the properties of metastable species and how they are affected by replacing the usual scalar product by the so called c-product. PMID- 26851915 TI - Lattice constants and expansivities of gas hydrates from 10 K up to the stability limit. AB - The lattice constants of hydrogenated and deuterated CH4-, CO2-, Xe- (clathrate structure type I) and N2-hydrates (clathrate structure type II) from 10 K up to the stability limit were established in neutron- and synchrotron diffraction experiments and were used to derive the related thermal expansivities. The following results emerge from this analysis: (1) The differences of expansivities of structure type I and II hydrates are fairly small. (2) Despite the larger guest-size of CO2 as compared to methane, CO2-hydrate has the smaller lattice constants at low temperatures, which is ascribed to the larger attractive guest host interaction of the CO2-water system. (3) The expansivity of CO2-hydrate is larger than for CH4-hydrate which leads to larger lattice constants for the former at temperatures above ~150 K; this is likely due to the higher motional degrees of freedom of the CO2 guest molecules. (4) The cage occupancies of Xe- and CO2-hydrates affect significantly the lattice constants. (5) Similar to ice Ih, the deuterated compounds have generally slightly larger lattice constants which can be ascribed to the somewhat weaker H-bonding. (6) Compared to ice Ih, the high temperature expansivities are about 50% larger; in contrast to ice Ih and the empty hydrate, there is no negative thermal expansion at low temperature. (7) A comparison of the experimental results with lattice dynamical work, with models based on an Einstein oscillator model, and results from inelastic neutron scattering suggest that the contribution of the guest atoms' vibrational energy to thermal expansion is important, most prominently for CO2- and Xe-hydrates. PMID- 26851916 TI - On the mean kinetic energy of the proton in strong hydrogen bonded systems. AB - The mean atomic kinetic energies of the proton, Ke(H), and of the deuteron, Ke(D), were calculated in moderate and strongly hydrogen bonded (HB) systems, such as the ferro-electric crystals of the KDP type (XH2PO4, X = K, Cs, Rb, Tl), the DKDP (XD2PO4, X = K, Cs, Rb) type, and the X3H(SO4)2 superprotonic conductors (X = K, Rb). All calculations utilized the simulated partial phonon density of states, deduced from density functional theory based first-principle calculations and from empirical lattice dynamics simulations in which the Coulomb, short range, covalent, and van der Waals interactions were accounted for. The presently calculated Ke(H) values for the two systems were found to be in excellent agreement with published values obtained by deep inelastic neutron scattering measurements carried out using the VESUVIO instrument of the Rutherford Laboratory, UK. The Ke(H) values of the M3H(SO4)2 compounds, in which the hydrogen bonds are centro-symmetric, are much lower than those of the KDP type crystals, in direct consistency with the oxygen-oxygen distance ROO, being a measure of the HB strength. PMID- 26851917 TI - Could the description on polynuclear superhalogens by DFT be comparable with high level ab initio results? A comparison between DFT and CCSD(T). AB - A systematic density functional theory study including 17 exchange-correlation functionals was performed on different types of superhalogens with high level coupled-cluster single double including perturbative triple excitations (CCSD(T)) results as the reference. The superhalogens selected here cover the ranges from mononuclear to polynuclear structures and from structures with halogen-atom ligands to those with non-halogen ligands, e.g., [MgX3](-), [Mg2X5](-), and [Mg3X7](-) (X = F, Cl, CN). It is clearly indicated that three double-hybrid functionals B2T-PLYP, B2GP-PLYP, B2K-PLYP as well as the range-separated hybrid functional omegaB97X are capable of providing results which approach the accuracy at the CCSD(T) level. The basis set effect is usually moderate and, in most cases, it is enough to utilize the basis set of triple-xi quality, e.g., Def2 TZVP. In addition, the results of the HF and MP2 method are also acceptable here, especially for polynuclear superhalogens where CCSD(T) is probably unpractical. PMID- 26851918 TI - Ab initio 3D potential energy and dipole moment surfaces for the CH4-Ar complex: Collision-induced intensity and dimer content. AB - We present new three-dimensional potential energy surface (PES) and dipole moment surfaces (DMSs) for the CH4-Ar van der Waals system. Ab initio calculations of the PES and DMS were carried out using the closed-shell single- and double excitation coupled cluster approach with non-iterative perturbative treatment of triple excitations. The augmented correlation-consistent aug-cc-pVXZ (X = D,T,Q) basis sets were employed, and the energies obtained were then extrapolated to the complete basis set limit. The dipole moment surface was obtained using aug-cc pVTZ basis set augmented with mid-bond functions for better description of exchange interactions. The second mixed virial coefficient was calculated and compared to available experimental data. The equilibrium constant for true dimer formation was calculated using classical partition function based on the knowledge of ab initio PES. Temperature variations of the zeroth spectral moment of the rototranslational collision-induced band as well as its true dimer constituent were traced with the use of the Boltzmann-weighted squared induced dipole properly integrated over respective phase space domains. Height profiles for N2-N2, N2-H2, CH4-N2, (CH4)2, and CH4-Ar true bound dimers in Titan's atmosphere were calculated with the use of reliable ab initio PESs. PMID- 26851919 TI - Time-resolved photoelectron spectroscopy of a dinuclear Pt(II) complex: Tunneling autodetachment from both singlet and triplet excited states of a molecular dianion. AB - Time-resolved pump-probe photoelectron spectroscopy has been used to study the relaxation dynamics of gaseous [Pt2(MU-P2O5H2)4 + 2H](2-) after population of its first singlet excited state by 388 nm femtosecond laser irradiation. In contrast to the fluorescence and phosphorescence observed in condensed phase, a significant fraction of the photoexcited isolated dianions decays by electron loss to form the corresponding monoanions. Our transient photoelectron data reveal an ultrafast decay of the initially excited singlet (1)A2u state and concomitant rise in population of the triplet (3)A2u state, via sub-picosecond intersystem crossing (ISC). We find that both of the electronically excited states are metastably bound behind a repulsive Coulomb barrier and can decay via delayed autodetachment to yield electrons with characteristic kinetic energies. While excited state tunneling detachment (ESETD) from the singlet (1)A2u state takes only a few picoseconds, ESETD from the triplet (3)A2u state is much slower and proceeds on a time scale of hundreds of nanoseconds. The ISC rate in the gas phase is significantly higher than in solution, which can be rationalized in terms of changes to the energy dissipation mechanism in the absence of solvent molecules. [Pt2(MU-P2O5H2)4 + 2H](2-) is the first example of a photoexcited multianion for which ESETD has been observed following ISC. PMID- 26851920 TI - Complex multireference configuration interaction calculations for the K-vacancy Auger states of N(q+) (q = 2-5) ions. AB - K-vacancy Auger states of N(q+) (q = 2-5) ions are studied by using the complex multireference single- and double-excitation configuration interaction (CMRD-CI) method. The calculated resonance parameters are in good agreement with the available experimental and theoretical data. It shows that the resonance positions and widths converge quickly with the increase of the atomic basis sets in the CMRD-CI calculations; the standard atomic basis set can be employed to describe the atomic K-vacancy Auger states well. The strong correlations between the valence and core electrons play important roles in accurately determining those resonance parameters, Rydberg electrons contribute negligibly in the calculations. Note that it is the first time that the complex scaling method has been successfully applied for the B-like nitrogen. CMRD-CI is readily extended to treat the resonance states of molecules in the near future. PMID- 26851921 TI - A theoretical simulation of the resonant Raman spectroscopy of the H2O?Cl2 and H2O?Br2 halogen-bonded complexes. AB - The resonant Raman spectra of the H2O?Cl2 and H2O?Br2 halogen-bonded complexes have been studied in the framework of a 2-dimensional model previously used in the simulation of their UV-visible absorption spectra using time-dependent techniques. In addition to the vibrational progression along the dihalogen mode, a progression is observed along the intermolecular mode and its combination with the intramolecular one. The relative intensity of the inter to intramolecular vibrational progressions is about 15% for H2O?Cl2 and 33% for H2O?Br2. These results make resonant Raman spectra a potential tool for detecting the presence of halogen bonded complexes in condensed phase media such as clathrates and ice. PMID- 26851922 TI - Isotope effects of ground and lowest lying vibrational states of H(3-x)D(x)O2(-) complexes. AB - Isotope effects of the H3O2(-) anion are investigated. For this, the 24 lowest excited vibrational states of the H(3-x)D(x)O2(-) complexes, with x = 0-3, are computed using two different Hamiltonians, namely, a 7D reduced-dimensionality one with a numerical representation of the kinetic energy operator (KEO) and a 9D full-dimensionality Hamiltonian with an exact analytic KEO. The computations are carried out with the multiconfiguration time-dependent Hartree method. The obtained results show that bridge and terminal H-D exchange cause a variation in energy with or without a rearrangement of states. A clear rearrangement of fundamental modes is observed in bridge H-D exchange of the H3O2(-) complex, where the frequency of bridge hydrogen stretching (z) is strongly lowered by substitution. The isotope effects show that rotation (phi), rocking (u1 + u2), wagging (u1 - u2), and O-O stretch (R) modes are sensitive to terminal H-D exchange, while the bridge-atom bending (x,y) and stretch (z) modes are sensitive to bridge H-D exchange. An influence coefficient, which measures the influence of an excitation of one mode on the various 1D reduced densities, is defined and analyzed in detail. It is shown that the D3O2(-) complex is more strongly correlated or coupled than the other isotopologues. PMID- 26851923 TI - Non-adiabatic dynamics of molecules in optical cavities. AB - Strong coupling of molecules to the vacuum field of micro cavities can modify the potential energy surfaces thereby opening new photophysical and photochemical reaction pathways. While the influence of laser fields is usually described in terms of classical field, coupling to the vacuum state of a cavity has to be described in terms of dressed photon-matter states (polaritons) which require quantized fields. We present a derivation of the non-adiabatic couplings for single molecules in the strong coupling regime suitable for the calculation of the dressed state dynamics. The formalism allows to use quantities readily accessible from quantum chemistry codes like the adiabatic potential energy surfaces and dipole moments to carry out wave packet simulations in the dressed basis. The implications for photochemistry are demonstrated for a set of model systems representing typical situations found in molecules. PMID- 26851924 TI - A theoretical investigation of the structural and electronic properties of 55 atom nanoclusters: The examples of Y-Tc and Pt. AB - Several studies have found that the Pt55 nanocluster adopts a distorted reduced core structure, DRC55, in which there are 8-11 atoms in the core and 47-44 atoms in the surface, instead of the compact and high-symmetry icosahedron structure, ICO55, with 13 and 42 atoms in the core and surface, respectively. The DRC structure has also been obtained as the putative global minimum configuration (GMC) for the Zn55 (3d), Cd55 (4d), and Au55 (5d) systems. Thus, the DRC55 structure has been reported only for systems with a large occupation of the d states, where the effects of the occupation of the valence anti-bonding d-states might play an important role. Can we observe the DRC structure for 55-atom transition-metal systems with non-occupation of the anti-bonding d-states? To address this question, we performed a theoretical investigation of the Y 55, Zr55, Nb55, Mo55, Tc55, and Pt55 nanoclusters, employing density functional theory calculations. For the putative GMCs, we found that the Y 55 adopts the ICO55 structure, while Nb55 and Mo55 adopt a bulk-like fragment based on the hexagonal close-packed structure and Tc55 adopts a face-centered cubic fragment; however, Zr55 adopts a DRC55 structure, like Zn55, Cd55, Pt55, and Au55. Thus we can conclude that the preference for DRC55 structure is not related to the occupation of the anti-bonding d-states, but to a different effect, in fact, a combination of structural and electronic effects. Furthermore, we obtained that the binding energy per atom follows the occupation of the bonding and anti bonding model, i.e., the stability of the studied systems increases from Y to Tc with a small oscillation for Mo, which also explains the equilibrium bond lengths. We obtained a larger magnetic moment for Y 55 (31 MUB) which can be explained by the localization of the d-states in Y at nanoscale, which is not observed for the remaining systems (0-1 MUB). PMID- 26851925 TI - (1)H NMR relaxometry and quadrupole relaxation enhancement as a sensitive probe of dynamical properties of solids--[C(NH2)3]3Bi2I9 as an example. AB - (1)H nuclear magnetic resonance relaxometry has been applied to reveal information on dynamics and structure of Gu3Bi2I9 ([Gu = C(NH2)3] denotes guanidinium cation). The data have been analyzed in terms of a theory of quadrupole relaxation enhancement, which has been extended here by including effects associated with quadrupole ((14)N) spin relaxation caused by a fast fluctuating component of the electric field gradient tensor. Two motional processes have been identified: a slow one occurring on a timescale of about 8 * 10(-6) s which has turned out to be (almost) temperature independent, and a fast process in the range of 10(-9) s. From the (1)H-(14)N relaxation contribution (that shows "quadrupole peaks") the quadrupole parameters, which are a fingerprint of the arrangement of the anionic network, have been determined. It has been demonstrated that the magnitude of the quadrupole coupling considerably changes with temperature and the changes are not caused by phase transitions. At the same time, it has been shown that there is no evidence of abrupt changes in the cationic dynamics and the anionic substructure upon the phase transitions. PMID- 26851926 TI - Viscoelasticity of glycerol at ultra-high frequencies investigated via molecular dynamics simulations. AB - We present a calculation of the shear and longitudinal moduli of glycerol in the gigahertz frequency regime and temperature range between 273 K and 323 K using classical molecular dynamics simulations. The full frequency spectra of shear and longitudinal moduli of glycerol between 0.5 GHz and 100 GHz at room temperature are computed, which was not previously available from experiments or simulations. We also demonstrate that the temperature dependence of the real parts of the shear and longitudinal moduli agrees well with available experimental counterparts obtained via time-domain Brillouin scattering. This work provides new insights into the response of molecular liquids to ultra-high frequency excitation and opens a new pathway for studying simple liquids at high frequencies and strain rates. PMID- 26851927 TI - High pressure dielectric studies on the structural and orientational glass. AB - High pressure dielectric studies on the H-bonded liquid D-glucose and Orientationally Disordered Crystal (ODIC) 1,6-anhydro-D-glucose (levoglucosan) were carried out. It was shown that in both compounds, the structural relaxation is weakly sensitive to compression. It is well reflected in the low pressure coefficient of the glass transition and orientational glass transition temperatures which is equal to 60 K/GPa for both D-glucose and 1,6-anhydro-D glucose. Although it should be noted that ?Tg(0)/?p evaluated for the latter compound seems to be enormously high with respect to other systems forming ODIC phase. We also found that the shape of the alpha-loss peak stays constant for the given relaxation time independently on the thermodynamic condition. Consequently, the Time Temperature Pressure (TTP) rule is satisfied. This experimental finding seems to be quite intriguing since the TTP rule was shown to work well in the van der Waals liquids, while in the strongly associating compounds, it is very often violated. We have also demonstrated that the sensitivity of the structural relaxation process to the temperature change measured by the steepness index (mp) drops with pressure. Interestingly, this change is much more significant in the case of D-glucose with respect to levoglucosan, where the fragility changes only slightly with compression. Finally, kinetics of ODIC-crystal phase transition was studied at high compression. It is worth mentioning that in the recent paper, Tombari and Johari [J. Chem. Phys. 142, 104501 (2015)] have shown that ODIC phase in 1,6-anhydro-D-glucose is stable in the wide range of temperatures and there is no tendency to form more ordered phase at ambient pressure. On the other hand, our isochronal measurements performed at varying thermodynamic conditions indicated unquestionably that the application of pressure favors solid (ODIC) solid (crystal) transition in 1,6-anhydro-D-glucose. This result mimics the impact of pressure on the crystallization of fully disordered supercooled van der Waals liquids. PMID- 26851928 TI - H-bonding of an NH(3) gas molecule to H(2)O/Pt(111)--A barrier-free path. AB - Does an OH-flipping barrier hinder H-bond formation between a gas phase molecule and a water monolayer whose free OH ligands point toward a substrate? According to density functional theory calculations for water on Pt(111) the answer is yes, when the molecule is CO or N2, but no when it is NH3. The difference is the relatively strong attraction of the NH3 lone pair to free OH ligands. PMID- 26851929 TI - Surface tension of the two center Lennard-Jones plus point dipole fluid. AB - Molecular dynamics simulations are used for systematically studying the surface tension of the two center Lennard-Jones plus point dipole (2CLJD) model fluid. In a dimensionless representation, this model fluid has two parameters describing the elongation and the dipole moment. These parameters were varied in the entire range relevant for describing real fluids resulting in a grid of 38 individual models. For each model, the surface tension was determined at temperatures between 60% and 90% of the critical temperature. For completeness, the vapor pressure and the saturated densities were also determined. The latter results agree well with the literature data, whereas for the surface tension, only few data were previously available. From the present results, an empirical correlation for the surface tension of the 2CLJD model as a function of the model parameters is developed. The correlation is used to predict the surface tension of 46 2CLJD molecular models from the literature, which were adjusted to bulk properties, but not to interfacial properties. The results are compared to the experimental data. The molecular models overestimate the surface tension, and deviations between the predictions and experimental data are below 12% on average. PMID- 26851930 TI - Observation of Fano line shapes in infrared vibrational spectra of CO2 adsorbed on Cu(997) and Cu(111). AB - Adsorption states of carbon dioxide on the Cu(997) and Cu(111) surfaces were investigated by infrared reflection absorption spectroscopy, temperature programmed desorption, and X-ray photoelectron spectroscopy. CO2 molecules are physisorbed on the Cu(997) surface at temperatures below 70 K; neither chemisorption nor dissociation of CO2 occurs on the Cu(997) surface at this low temperature. However, the vibrational spectra of adsorbed CO2 depend significantly on the substrate temperature and coverage. IR spectra of CO2 vibrational modes at 70 K show asymmetric Fano line shapes, while only normal absorption bands are observed when CO2 is adsorbed at 20 K. Fano line shapes are also observed for CO2 on Cu(111) at 85 K. The observation of Fano effect indicates the coupling between the electronic continuum states of the Cu surface and the internal vibrational modes of CO2 even in such physisorbed system. PMID- 26851931 TI - Self-diffusion in the non-Newtonian regime of shearing liquid crystal model systems based on the Gay-Berne potential. AB - The self-diffusion coefficients of nematic phases of various model systems consisting of regular convex calamitic and discotic ellipsoids and non-convex bodies such as bent-core molecules and soft ellipsoid strings have been obtained as functions of the shear rate in a shear flow. Then the self-diffusion coefficient is a second rank tensor with three different diagonal components and two off-diagonal components. These coefficients were found to be determined by a combination of two mechanisms, which previously have been found to govern the self-diffusion of shearing isotropic liquids, namely, (i) shear alignment enhancing the diffusion in the direction parallel to the streamlines and hindering the diffusion in the perpendicular directions and (ii) the distortion of the shell structure in the liquid whereby a molecule more readily can escape from a surrounding shell of nearest neighbors, so that the mobility increases in every direction. Thus, the diffusion parallel to the streamlines always increases with the shear rate since these mechanisms cooperate in this direction. In the perpendicular directions, these mechanisms counteract each other so that the behaviour becomes less regular. In the case of the nematic phases of the calamitic and discotic ellipsoids and of the bent core molecules, mechanism (ii) prevails so that the diffusion coefficients increase. However, the diffusion coefficients of the soft ellipsoid strings decrease in the direction of the velocity gradient because the broadsides of these molecules are oriented perpendicularly to this direction due the shear alignment (i). The cross coupling coefficient relating a gradient of tracer particles in the direction of the velocity gradient and their flow in the direction of the streamlines is negative and rather large, whereas the other coupling coefficient relating a gradient in the direction of the streamlines and a flow in the direction of the velocity gradient is very small. PMID- 26851932 TI - Effective electrostatic interactions among charged thermo-responsive microgels immersed in a simple electrolyte. AB - This work explores the nature and thermodynamic behavior of the effective electrostatic interactions among charged microgels immersed in a simple electrolyte, taking special interest in the effects due to the thermally induced variation of the microgel size while the remaining parameters (microgel charge and concentration, plus the amount of added salt) are kept constant. To this end, the rigorous approach obtained from applying the precise methodology of the dressed ion theory to the proper definition of the effective direct correlation functions, which emerge from tracing-out the degrees of freedom of the microscopic ions, is employed to provide an exact description of the parameters characterizing such interactions: screening length, effective permittivity, and renormalized charges. A model solution with three components is assumed: large permeable anionic spheres for the microgels, plus small charged hard spheres of equal size for the monovalent cations and anions. The two-body correlations among the components of this model suspension, used as the input for the determination of the effective interaction parameters, are here calculated by using the hyper netted chain approximation. It is then found that at finite microgel concentrations the values of these parameters change as the microgel size increases, even though the ionic strength of the supporting electrolyte and the bare charge of the microgels remain fixed during this process. The variation of the screening length, as well as that of the effective permittivity, is rather small, but still interesting in view of the fact that the corresponding Debye length stays constant. The renormalized charges, in contrast, increase markedly as the microgels swell. The ratio of the renormalized charge to the corresponding analytic result obtained in the context of an extended linear response theory allows us to introduce an effective charge that accounts for the non-linear effects induced by the short-ranged association of microions to the microgels. The behavior of these effective charges as a function of the amount of added salt and the macroion charge, size, and concentration reveals the interplay among all these system parameters. PMID- 26851933 TI - The interplay of intrinsic disorder and macromolecular crowding on alpha synuclein fibril formation. AB - alpha-synuclein (alpha-syn) is an intrinsically disordered protein which is considered to be one of the causes of Parkinson's disease. This protein forms amyloid fibrils when in a highly concentrated solution. The fibril formation of alpha-syn is induced not only by increases in alpha-syn concentration but also by macromolecular crowding. In order to investigate the coupled effect of the intrinsic disorder of alpha-syn and macromolecular crowding, we construct a lattice gas model of alpha-syn in contact with a crowding agent reservoir based on statistical mechanics. The main assumption is that alpha-syn can be expressed as coarse-grained particles with internal states coupled with effective volume; and disordered states are modeled by larger particles with larger internal entropy than other states. Thanks to the simplicity of the model, we can exactly calculate the number of conformations of crowding agents, and this enables us to prove that the original grand canonical ensemble with a crowding agent reservoir is mathematically equivalent to a canonical ensemble without crowding agents. In this expression, the effect of macromolecular crowding is absorbed in the internal entropy of disordered states; it is clearly shown that the crowding effect reduces the internal entropy. Based on Monte Carlo simulation, we provide scenarios of crowding-induced fibril formation. We also discuss the recent controversy over the existence of helically folded tetramers of alpha-syn, and suggest that macromolecular crowding is the key to resolving the controversy. PMID- 26851934 TI - Note: A new truncation correction for the configurational temperature extends its applicability to interaction potentials with a discontinuous force. AB - We present a simple truncation correction for the configurational temperature which, unlike previous corrections, works even at low truncation values for the shifted and truncated Lennard-Jones potential. The success of the new correction suggests that the expression for the configurational temperature is valid also for interaction potentials with a discontinuous force, given that the discontinuity is properly accounted for. PMID- 26851935 TI - Erratum: "A transformed framework for dynamic correlation in multireference problems" [J. Chem. Phys. 142, 124107 (2015)]. PMID- 26851936 TI - Economic costs of fever to households in the middle belt of Ghana. AB - BACKGROUND: Malaria is one of the main health problems in the sub-Saharan Africa accounting for approximately 198 million morbidity and close to 600,000 mortality cases. Households incur out-of-pocket expenditure for treatment and lose income as a result of not being able to work or care for family members. The main objective of this survey was to assess the economic cost of treating malaria and/or fever with the new ACT to households in the Kintampo districts of Ghana where a health and demographic surveillance systems (KHDSS) are set up to document population dynamics. METHODS: The study was a cross-sectional survey conducted from October 2009 to July 2011 using community members' accessed using KHDSS population in the Kintampo area. An estimated sample size of 4226 was randomly selected from the active members of the KHDSS. A structured questionnaire was administered to the selected populates who reported of fever within the last 2 weeks prior to the visit. Data was collected on treatment seeking behaviour, direct and indirect costs of malaria from the patient perspective. RESULTS: Of the 4226 households selected, 947 households with 1222 household members had fever out of which 92 % sought treatment outside home; 55 % of these were females. 31.6 % of these patients sought care from chemical shops. A mean amount of GHS 4.2 (US$2.76) and GHS 18.0 (US$11.84) were incurred by households as direct and indirect cost respectively. On average a household incurred a total cost of GHS 22.2 (US$14.61) per patient per episode. Total economic cost was lowest for those in the highest quintile and highest for those in the middle quintile. CONCLUSION: The total cost of treating fever/malaria episode is relatively high in the study area considering the poverty levels in Ghana. The NHIS has positively influenced health-seeking behaviours and reduced the financial burden of seeking care for those that are insured. PMID- 26851937 TI - Ultrasound guided double injection of blood into cisterna magna: a rabbit model for treatment of cerebral vasospasm. AB - BACKGROUND: Double injection of blood into cisterna magna using a rabbit model results in cerebral vasospasm. An unacceptably high mortality rate tends to limit the application of model. Ultrasound guided puncture can provide real-time imaging guidance for operation. The aim of this paper is to establish a safe and effective rabbit model of cerebral vasospasm after subarachnoid hemorrhage with the assistance of ultrasound medical imaging. METHODS: A total of 160 New Zealand white rabbits were randomly divided into four groups of 40 each: (1) manual control group, (2) manual model group, (3) ultrasound guided control group, and (4) ultrasound guided model group. The subarachnoid hemorrhage was intentionally caused by double injection of blood into their cisterna magna. Then, basilar artery diameters were measured using magnetic resonance angiography before modeling and 5 days after modeling. RESULTS: The depth of needle entering into cisterna magna was determined during the process of ultrasound guided puncture. The mortality rates in manual control group and model group were 15 and 23 %, respectively. No rabbits were sacrificed in those two ultrasound guided groups. We found that the mortality rate in ultrasound guided groups decreased significantly compared to manual groups. Compared with diameters before modeling, the basilar artery diameters after modeling were significantly lower in manual and ultrasound guided model groups. The vasospasm aggravated and the proportion of severe vasospasms was greater in ultrasound guided model group than that of manual group. In manual model group, no vasospasm was found in 8 % of rabbits. CONCLUSIONS: The ultrasound guided double injection of blood into cisterna magna is a safe and effective rabbit model for treatment of cerebral vasospasm. PMID- 26851938 TI - Scenario drafting for early technology assessment of next generation sequencing in clinical oncology. AB - BACKGROUND: Next Generation Sequencing (NGS) is expected to lift molecular diagnostics in clinical oncology to the next level. It enables simultaneous identification of mutations in a patient tumor, after which targeted therapy may be assigned. This approach could improve patient survival and/or assist in controlling healthcare costs by offering expensive treatment to only those likely to benefit. However, NGS has yet to make its way into the clinic. Health Technology Assessment can support the adoption and implementation of a novel technology, but at this early stage many of the required variables are still unknown. METHODS: Scenario drafting and expert elicitation via a questionnaire were used to identify factors that may act as a barrier or facilitate adoption of NGS-based molecular diagnostics. Attention was paid to predominantly elicit quantitative answers, allowing their use in future modelling of cost effectiveness. RESULTS: Adequately informing patients and physicians, the latters' opinion on clinical utility and underlying evidence as well as presenting sequencing results within a relevant timeframe may act as pivotal facilitators. Reimbursement for NGS-based testing and accompanying therapies (both general and in case of off-label prescription) was found to be a potential barrier. Competition on the market and demonstrating clinical utility may also be challenging. Importantly, numerous quantitative values for variables related to each of these potential barriers/facilitators, such as such as desired panel characteristics, willingness to pay or the expected number of targets identified per person, were also elicited. CONCLUSIONS: We have identified several factors that may either pose a barrier or facilitate the adoption of NGS in the clinic. We believe acting upon these findings, for instance by organizing educational events, advocating new ways of evidence generation and steering towards the most cost-effective solution, will accelerate the route from bench-to-bedside. Moreover, due to the methodology of expert elicitation, this study provides parameters that can be incorporated in future cost-effectiveness modeling to steer the development of NGS gene panels towards the most optimal direction. PMID- 26851939 TI - Primary care characteristics and their association with health screening in a low socioeconomic status public rental-flat population in Singapore- a mixed methods study. AB - BACKGROUND: In Singapore, subsidized primary care is provided by centralized polyclinics; since 2000, policies have allowed lower-income Singaporeans to utilize subsidies at private general-practitioner (GP) clinics. We sought to determine whether proximity to primary care, subsidised primary care, or having regular primary care associated with health screening participation in a low socioeconomic-status public rental-flat community in Singapore. METHODS: From 2009-2014, residents in five public rental-flat enclaves (N = 936) and neighboring owner-occupied precincts (N = 1060) were assessed for participation in cardiovascular and cancer screening. We then evaluated whether proximity to primary care, subsidised primary care, or having regular primary care associated with improved adherence to health screening. We also investigated attitudes to health screening using qualitative methodology. RESULTS: In the rental flat population, for cardiovascular screening, regular primary care was independently associated with regular diabetes screening (adjusted odds ratio, aOR = 1.59, CI = 1.12-2.26, p = 0.009) and hyperlipidemia screening (aOR = 1.82, CI = 1.10-3.04, p = 0.023). In the owner-occupied flats, regular primary care was independently associated with regular hypertension screening (aOR = 9.34 (1.82-47.85, p = 0.007), while subsidized primary care was associated with regular diabetes screening (aOR = 2.94, CI = 1.04-8.31, p = 0.042). For cancer screening, in the rental flat population, proximity to primary care was associated with less participation in regular colorectal cancer screening (aOR = 0.42, CI = 0.17-0.99, p = 0.049) and breast cancer screening (aOR = 0.29, CI = 0.10-0.84, p = 0.023). In the owner-occupied flat population, for gynecological cancer screening, usage of subsidized primary care and proximity to primary care was associated with higher rates of breast cancer and cervical cancer screening; however, being on regular primary care followup was associated with lower rates of mammography (aOR = 0.10, CI = 0.01-0.75, p = 0.025). On qualitative analysis, patients were discouraged from screening by distrust in the doctor-patient relationship; for cancer screening in particular, patients were discouraged by potential embarrassment. CONCLUSIONS: Regular primary care was independently associated with regular participation in cardiovascular screening in both low-SES and higher SES communities. However, for cancer screening, in the low-SES community, proximity to primary care was associated with less participation in regular screening, while in the higher-SES community, regular primary care was associated with lower screening participation; possibly due to embarrassment regarding screening modalities. PMID- 26851940 TI - Relationships of physical activity and sedentary time in obese parent-child dyads: a cross-sectional study. AB - BACKGROUND: Research suggests physical activity is linked to obesity. Further, the physical activity of healthy parents and their children is associated with each other. However, this relationship has not been examined in obese parents and their obese children. METHODS: The purpose of this study was to compare the physical activity and sedentary time of obese, low-income, ethnic minority parents and their children on weekdays and weekend days using accelerometry. Data were obtained from eight rural sites in the middle and eastern part of North Carolina (N.C.), United States (U.S.) from 2007-2010 using a rolling enrollment. One hundred and ninety-nine obese parents (94 % female) and their obese children (54 % female) wore accelerometers simultaneously for three weekdays and one weekend day. Total physical activity, moderate-to-vigorous physical activity (MVPA) and sedentary time and proportions were determined. RESULTS: Parents' and children's total physical activity and MVPA levels were lower on weekend days than weekdays. Total counts per minute for children on weekdays and weekend days were greater than for parents (p < 0.001). Total counts per minute were more highly correlated on weekend days than weekdays (r = 0.352, p < 0.0002 versus r = 0.165, p < 0.025). Parents' performed MVPA for 14 (SD = +/-25) and 9 (SD = +/-16) minutes/day on weekdays and weekend days, respectively; children performed MVPA for 37 (SD = +/-25) and 31(SD = +/-38) minutes/day for weekdays and weekend days, respectively. Correlations between parents and children for MVPA were higher on weekend days versus weekdays (r = 0.253 and 0.177, respectively; p < 0.015). Associations for sedentary time followed a similar trend, with r = 0.33 (p < 0.0002) for weekend days and r = 0.016 (p < 0.026) for weekdays. Associations between obese parent-child dyads on sedentary time were stronger for girls, while associations between dyads on MVPA were stronger for boys. However, formal interaction analyses were not significant (p > 0.13). DISCUSSION: Since physical activity levels of obese parents and their obese child are somewhat related, especially on weekend days, combined parent-child obesity programs focused on reducing sedentary time could be beneficial, particularly for the child. CONCLUSION: In conclusion, this study of the physical activity levels of obese parents and their obese children found some relationships between the parents' and children's physical activity and sedentary behavior patterns, especially on weekend days. TRIAL REGISTRATION: NCT01378806 . PMID- 26851941 TI - Qualitative analysis of programmatic initiatives to text patients with mobile devices in resource-limited health systems. AB - BACKGROUND: Text messaging is an affordable, ubiquitous, and expanding mobile communication technology. However, safety net health systems in the United States that provide more care to uninsured and low-income patients may face additional financial and infrastructural challenges in utilizing this technology. Formative evaluations of texting implementation experiences are limited. We interviewed safety net health systems piloting texting initiatives to study facilitators and barriers to real-world implementation. METHODS: We conducted telephone interviews with various stakeholders who volunteered from each of the eight California-based safety net systems that received external funding to pilot a texting-based program of their choosing to serve a primary care need. We developed a semi structured interview guide based partly on the Consolidated Framework for Implementation Research (CFIR), which encompasses several domains: the intervention, individuals involved, contextual factors, and implementation process. We inductively and deductively (using CFIR) coded transcripts, and categorized themes into facilitators and barriers. RESULTS: We performed eight interviews (one interview per pilot site). Five sites had no prior texting experience. Sites applied texting for programs related to medication adherence and monitoring, appointment reminders, care coordination, and health education and promotion. No site texted patient-identifying health information, and most sites manually obtained informed consent from each participating patient. Facilitators of implementation included perceived enthusiasm from patients, staff and management belief that texting is patient-centered, and the early identification of potential barriers through peer collaboration among grantees. Navigating government regulations that protect patient privacy and guide the handling of protected health information emerged as a crucial barrier. A related technical challenge in five sites was the labor-intensive tracking and documenting of texting communications due to an inability to integrate texting platforms with electronic health records. CONCLUSIONS: Despite enthusiasm for the texting programs from the involved individuals and organizations, inadequate data management capabilities and unclear privacy and security regulations for mobile health technology slowed the initial implementation and limited the clinical use of texting in the safety net and scope of pilots. Future implementation work and research should investigate how different texting platform and intervention designs affect efficacy, as well as explore issues that may affect sustainability and the scalability. PMID- 26851942 TI - Design, structure prediction and molecular dynamics simulation of a fusion construct containing malaria pre-erythrocytic vaccine candidate, PfCelTOS, and human interleukin 2 as adjuvant. AB - BACKGROUND: Malaria infection is still widespread in some parts of the world and threatens the lives of millions of people every year. Vaccines, especially oral vaccines are considered to be effective in reducing the burden of malaria morbidity and mortality. By using recombinant technology, suitable oral hosts could serve as antigen delivering vehicles in developing oral vaccines. This study was aimed towards designing and computational analysis of a fusion protein consisting of Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (PfCelTOS) fused to human interleukin-2 (IL-2) and M cell-specific peptide ligand (Co1), as a step toward developing a vaccine candidate. RESULTS: To our best knowledge, the three dimensional (3D) structure of CelTOS is not reported in protein database. Therefore, we carried out computational modeling and simulation in the hope of understanding the properties and structure of PfCelTOS. Then we fused IL-2 to PfCelTOS by a flexible linker and did in silico analysis to confirm the proper folding of each domain in the designed fusion protein. In the last step, Co1 ligand was added to the confirmed fusion structure using a rigid linker and computational analysis was performed to evaluate the final fusion construct. One structure out of five predicted by I-TASSER for PfCelTOS and fusion constructs was selected based on the highest value for C score. Molecular dynamics (MD) simulation analysis indicated that predicted structures are stable during the simulation. Ramchandran Plot analysis of PfCelTOS and fusion constructs before and after MD simulation also represented that most residues were fallen in favorable regions. CONCLUSION: In silico study showed that Co1-(AEEEK)3- IL-2-(GGGGS)3-PfCelTOS construct has a constant structure and the selected linkers are effectively able to separate the domains. Therefore, data reported in this paper represents the first step toward developing of an oral vaccine candidate against malaria infection. PMID- 26851943 TI - Early traumatic experiences, perceived discrimination and conversion to psychosis in those at clinical high risk for psychosis. AB - PURPOSE: There is evidence to suggest that both early traumatic experiences and perceived discrimination are associated with later onset of psychosis. Less is known about the impact these two factors may have on conversion to psychosis in those who are at clinical high risk (CHR) of developing psychosis. The purpose of this study was to determine if trauma and perceived discrimination were predictors of conversion to psychosis. METHODS: The sample consisted of 764 individuals who were at CHR of developing psychosis and 280 healthy controls. All participants were assessed on past trauma, bullying and perceived discrimination. RESULTS: Individuals at CHR reported significantly more trauma, bullying and perceived discrimination than healthy controls. Only perceived discrimination was a predictor of later conversion to psychosis. CONCLUSIONS: Given that CHR individuals are reporting increased rates of trauma and perceived discrimination, these should be routinely assessed, with the possibility of offering interventions aimed at ameliorating the impact of past traumas as well as improving self-esteem and coping strategies in an attempt to reduce perceived discrimination. PMID- 26851944 TI - Cancer-associated fibroblasts promote the progression of endometrial cancer via the SDF-1/CXCR4 axis. AB - BACKGROUND: Cancer-associated fibroblasts (CAFs) are believed to play an essential role in cancer initiation and development. However, little research has been undertaken to evaluate the role of CAFs in endometrial cancer (EC) progression. We aim to detect the functional contributions of CAFs to promote progression of EC. METHODS: Stromal fibroblasts were isolated from endometrioid adenocarcinomas and normal endometrial tissues. The conditioned media of cultured CAFs and normal fibroblasts (NFs) were collected to detect the level of stromal cell-derived factor-1alpha (SDF-1alpha), macrophage chemoattractant protein-1 (MCP-1), migration inhibitory factor (MIF), colony stimulating factor-1 (CSF-1), and interleukin-1 (IL-1) by ELISA. The CAFs or NFs were cocultured with EC cell lines to determine the proliferation, migration, and invasion by MTT assays and transwell chambers. Xenograft models were used to observe tumor growth. Matrix metalloproteinases (MMP)-2 and MMP-9 activity was evaluated by zymography. AMD3100 (a chemokine receptor 4 (CXCR4) antagonist) was used to block the SDF 1/CXCR4 axis. Neutralizing antibodies were used to detect PI3K/Akt and MAPK/Erk pathways by western blotting. SDF-1alpha and CXCR4 expressions were analyzed in xenotransplanted tumors and 348 cases by immunohistochemistry. RESULTS: CAFs promoted proliferation, migration, and invasion as well as in vivo tumorigenesis of admixed EC cells significantly more than NFs by secreting SDF-1alpha. These effects were significantly inhibited by AMD3100. CAFs promoted EC progression via the SDF-1alpha/CXCR4 axis to activate the PI3K/Akt and MAPK/Erk signalings in a paracrine-dependent manner or increase MMP-2 and MMP-9 secretion in an autocrine dependent manner. SDF-1alpha and CXCR4 expression upregulation accompanied clinical EC development and progression. High SDF-1alpha expression levels were associated with deep myometrial invasion, lymph node metastasis, and poor prognosis in EC. CONCLUSIONS: Our data indicated that CAFs derived from EC tissues promoted EC progression via the SDF-1/CXCR4 axis in a paracrine- or autocrine-dependent manner. SDF-1alpha is a novel independent poor prognostic factor for EC patients' survival. Targeting the SDF-1/CXCR4 axis might provide a novel therapeutic strategy for EC treatment. PMID- 26851946 TI - BMC reproductive health: family planning global conference series. PMID- 26851945 TI - Genetic, Cellular and Clinical Features of ICF Syndrome: a French National Survey. AB - PURPOSE: Autosomal recessive deficiencies of DNMT3B or ZBTB24 account for two thirds of cases of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome). This primary immunodeficiency (PID) is characterized mainly by an antibody deficiency, facial abnormalities and centromeric instability. We analyzed the national cohort of patients with ICF syndrome with the aim of providing a more detailed description of the phenotype and management of patients with ICF syndrome. METHODS: Demographic, genetic, immunological, and clinical features were recorded for each patient. RESULTS: In the French cohort, seven of the nine patients carried DNMT3B mutations, six of which had never been described before. One patient had compound heterozygous ZBTB24 mutations. All patients were found to lack CD19(+)CD27(+) memory B cells. This feature is a major diagnostic criterion for both ICF1 and ICF2. Patients suffered both bacterial and viral infections, and three patients developed bronchiectasis. Autoimmune manifestations (hepatitis, nephritis and thyroiditis) not previously reported in ICF1 patients were also detected in two of our ICF1 patients. The mode of treatment and outcome of the French patients are reported, by genetic defect, and compared with those for 68 previously reported ICF patients. Immunoglobulin (Ig) replacement treatment was administered to all nine French patients. One ICF1 patient presented severe autoimmune manifestations and pancytopenia and underwent allogeneic hematopoietic stem cell transplantation (HSCT), but she died from unknown causes 6 years post-transplant. CONCLUSION: Autoimmune signs are uncommon in ICF syndrome, but, when present, they affect patient outcome and require immunosuppressive treatment. The long-term outcome of ICF patients has been improved by the combination of IgG replacement and antibiotic prophylaxis. PMID- 26851947 TI - A mild form of dermatomyositis as a prodromal sign of lung adenocarcinoma: a case report. AB - BACKGROUND: Dermatomyositis is an idiopathic connective tissue disease characterized by specific cutaneous findings and inflammatory lesions in the muscle biopsy. An association between dermatomyositis and malignancy, including breast, ovarian, lung and colon cancer was recognized many years ago, with an incidence of malignancy in approximately 20 % of cases. Dermatomyositis is hypothesized to be an autoimmune reaction against factors or hormones secreted by the tumor; however, the exact autoimmune mechanism of the disease pathogenesis remains unknown. CASE PRESENTATION: Here we report a case of a woman with dermatomyositis who was diagnosed with lung adenocarcinoma in the setting of weight loss, progressive fatigue and muscle weakness. A 43-year-old Caucasian woman was referred to our hospital by her physician for suspected contact dermatitis since she described mild itching sensations in her arms and legs as her major symptom. A physical examination revealed erythematous papular lesions over her metacarpophalangeal and proximal interphalangeal joints together with a periungual involvement with redness, hyperkeratosis and capillary telangiectasia along the distal nailfolds on her hands. She was unaware of these features and they did not seem to bother her. A thorough examination of her medical history, however, revealed more symptoms. Pain and weakness in the muscles of her proximal extremities and neck flexor muscles led to difficulty in raising her arms and climbing stairs. At the same time she experienced swallowing difficulties and reported an uncharacteristic weight loss of 10 kg in the last 3 months. The results of laboratory tests showed increased values of serum creatine kinase and myoglobin. An electromyogram, a skin biopsy and a muscle biopsy confirmed the diagnosis of dermatomyositis. A computed tomography of her thorax showed a nodular mass in the upper lobe of her right lung. A histological examination of the lung biopsy showed an adenocarcinoma of moderate differentiation. She was diagnosed with paraneoplastic dermatomyositis as the first sign of a lung adenocarcinoma. CONCLUSIONS: Our case report highlights the importance of a thorough search for underlying malignancy in patients with dermatomyositis even if dermatomyositis has a mild appearance or a discrete skin manifestation. PMID- 26851948 TI - A comparative hospital-based observational study of mono- and co-infections of malaria, dengue virus and scrub typhus causing acute undifferentiated fever. AB - Positive serology for dengue and/or scrub typhus infection with/without positive malarial smear (designated as mixed or co-infection) is being increasingly observed during epidemics of acute undifferentiated febrile illnesses (AUFIs). We planned to study the clinical and biochemical spectrum of co-infections with Plasmodium sp., dengue virus and scrub typhus and compare these with mono infection by the same organisms. During the period from December 2012 to December 2013, all cases presenting with AUFIs to a single medical unit of a referral centre in Garhwal region of the north Indian state of Uttarakhand were retrospectively selected and categorised aetiologically as co-infections, malaria, dengue or scrub typhus. The groups thus created were compared in terms of demographic, clinical, biochemical and outcome parameters. The co-infection group (n = 49) was associated with milder clinical manifestations, fewer, milder and non-progressive organ dysfunction, and lesser need for intensive care, mechanical ventilation and dialysis as compared to mono-infections. When co infections were sub-grouped and compared with the relevant mono-infections, there were differences in certain haematological and biochemical parameters; however, this difference did not translate into differential outcomes. Scrub typhus mono infection was associated with severe disease in terms of both morbidity and mortality. Malaria, dengue and scrub typhus should be routinely tested in all patients with AUFIs. Co-infections, whether true or due to serological cross reactivity, appear to be a separate entity so far as presentation and morbidity is concerned. Further insight is needed into the mechanism and identification of the protective infection. PMID- 26851949 TI - Real-world effectiveness of peginterferon alpha-2b plus ribavirin in a Canadian cohort of treatment-naive chronic hepatitis C patients with genotypes 2 or 3: results of the PoWer and RediPEN studies. AB - The purpose of this investigation was to assess the real-life effectiveness of pegylated interferon (peg-IFN) alpha-2b with ribavirin (RBV) in a cohort of treatment-naive patients with chronic genotypes 2 (G2) or 3 (G3) hepatitis C virus (HCV) infection. A post-hoc pooled analysis of two Canadian multicenter, observational studies, RediPEN and PoWer, was carried out. A total of 1242 G2- or G3-infected patients were included. The primary outcome was sustained virologic response (SVR). Secondary endpoints included early virologic response (EVR), end of-treatment (EOT) response, and relapse. Multivariate logistic regression was used to identify independent predictors of treatment response. SVR in G2 and G3 was 74.4 % and 63.6 %, respectively. Relapse occurred in 12.7 % and 19.1 % of G2- and G3-infected patients achieving EOT response, respectively. Overall, G3 was found to independently predict reduced SVR [odds ratio (OR) = 0.20; p = 0.007] and increased relapse (OR = 6.84; p = 0.022). Among G3-infected patients, increasing fibrosis score was the most important factor predicting reduced SVR [F2 vs. F0/F1 (OR = 0.41; p = 0.009); F3 vs. F0/F1 (OR = 0.72; p = 0.338); F4 vs. F0/F1 (OR = 0.27; p = 0.001)]. Male gender (OR = 13.16; p = 0.020) and higher fibrosis score [F2 vs. F0/F1 (OR = 9.72; p = 0.016); F3/F4 vs. F0/F1 (OR = 4.23; p = 0.113)] were associated with increased relapse in G3 patients. These results support the real-life effectiveness of peg-IFN alpha-2b plus ribavirin in HCV G2- and G3-infected patients. Overall, genotype was identified as the most significant predictor of treatment outcome. Fibrosis score and gender were key outcome predictors in the G3-infected population. In clinical settings, peg INF/RBV offers an alternative for patients without access to all oral direct acting antivirals. PMID- 26851951 TI - Intravitreal aflibercept for myopic choroidal neovascularization. PMID- 26851950 TI - Maternal and neonatal FTO rs9939609 polymorphism affect insulin sensitivity markers and lipoprotein profile at birth in appropriate-for-gestational-age term neonates. AB - The influence of maternal fat mass and obesity (FTO) gene polymorphism on neonatal insulin sensitivity/resistance biomarkers and lipoprotein profile has not been tested. The study aimed to assess the association between the FTO rs9939609 polymorphism in mother-neonate couples and neonatal anthropometrical measurements, insulin sensitivity/resistance, and lipid and lipoprotein concentrations at birth. Fifty-three term, appropriate-for-gestational-age, Caucasian newborns together with their respective mothers participated in a cross sectional study. Sixty-six percent of mothers and neonates carried the A allele (being AA or AT). TT mothers gained less weight during pregnancy, but non significant maternal gene influence was found for neonatal bodyweight, body mass index, or ponderal index. Neonates from AA + AT mothers showed lower glucose, insulin, and homeostatic model assessment insulin resistance (HOMA-IR) but higher homeostatic model assessment insulin sensitivity (HOMA-IS) and homocysteine than neonates whose mothers were TT. AA + AT neonates had higher insulin and HOMA-IR than TT. The genotype neonatal * maternal association was tested in the following four groups of neonates: TT neonates * TT mothers (nTT * mTT), TT neonates * AA + AT mothers (nTT * mAA + AT), AA + AT neonates * TT mothers (nAA + AT * mTT), and AA + AT neonates * AA + AT mothers (nAA + AT * mAA + AT). Non-significant interactions between neonatal and maternal alleles were found for any parameter tested. However, maternal alleles affected significantly glucose, insulin, HOMA IR, and homocysteine while neonatal alleles the arylesterase activity. Most significant differences were found between nATT + AA * mTT and nATT + AA * mAA + AT. Glycemia, insulinemia, and HOMA-IR were lower, while the Mediterranean diet adherence (MDA) was higher in the mAA + AT vs. mTT whose children were AA + AT. This dietary fact seems to counterbalance the potential negative effect on glucose homeostasis of the obesogenic A allele in neonates. PMID- 26851952 TI - Size distribution characteristics of carbonaceous aerosol in Xishuangbanna, southwest China: a sign for biomass burning in Asia. AB - In 2012, size-segregated aerosol samples were collected in Xishuangbanna, a forest station in southwest China. The concentrations of organic and elemental carbon (OC and EC for short) were quantified with thermal/optical carbon analyzer in the filter samples. OC and EC exhibited similar seasonal patterns, with the highest concentrations in spring, possibly due to the influence of biomass burning in south and southeast Asia. The mass size distributions of OC and EC were bimodal in all the sampling seasons, each with a dominant peak in the fine mode of 0.4-0.7 MUm and a coarse peak in the size range of 2.1-4.7 MUm. In fine mode, OC and EC showed smaller geometric mean diameters (GMDs) during winter. OC and EC were prone to be more concentrated in fine particles in spring and winter than in summer and autumn. Furthermore, EC was more abundant in fine particles than OC. Good correlations (R(2) = 0.75-0.82) between OC and EC indicated that they had common dominant sources of combustion such as biomass burning and fossil fuel combustion emissions. The daily average OC/EC ratios ranged from 2.1 to 9.1, more elevated OC/EC ratios being found in the winter. PMID- 26851954 TI - Three-dimensional morphology study of surgical adolescent idiopathic scoliosis patient from encoded geometric models. AB - PURPOSE: The classification of three-dimensional (3D) spinal deformities remains an open question in adolescent idiopathic scoliosis. Recent studies have investigated pattern classification based on explicit clinical parameters. An emerging trend however seeks to simplify complex spine geometries and capture the predominant modes of variability of the deformation. The objective of this study is to perform a 3D characterization and morphology analysis of the thoracic and thoraco/lumbar scoliotic spines (cross-sectional study). The presence of subgroups within all Lenke types will be investigated by analyzing a simplified representation of the geometric 3D reconstruction of a patient's spine, and to establish the basis for a new classification approach based on a machine learning algorithm. METHODS: Three-dimensional reconstructions of coronal and sagittal standing radiographs of 663 patients, for a total of 915 visits, covering all types of deformities in adolescent idiopathic scoliosis (single, double and triple curves) and reviewed by the 3D Classification Committee of the Scoliosis Research Society, were analyzed using a machine learning algorithm based on stacked auto-encoders. The codes produced for each 3D reconstruction would be then grouped together using an unsupervised clustering method. For each identified cluster, Cobb angle and orientation of the plane of maximum curvature in the thoracic and lumbar curves, axial rotation of the apical vertebrae, kyphosis (T4-T12), lordosis (L1-S1) and pelvic incidence were obtained. No assumptions were made regarding grouping tendencies in the data nor were the number of clusters predefined. RESULTS: Eleven groups were revealed from the 915 visits, wherein the location of the main curve, kyphosis and lordosis were the three major discriminating factors with slight overlap between groups. Two main groups emerge among the eleven different clusters of patients: a first with small thoracic deformities and large lumbar deformities, while the other with large thoracic deformities and small lumbar curvature. The main factor that allowed identifying eleven distinct subgroups within the surgical patients (major curves) from Lenke type-1 to type-6 curves, was the location of the apical vertebra as identified by the planes of maximum curvature obtained in both thoracic and thoraco/lumbar segments. Both hypokyphotic and hyperkypothic clusters were primarily composed of Lenke 1-4 curve type patients, while a hyperlordotic cluster was composed of Lenke 5 and 6 curve type patients. CONCLUSION: The stacked auto-encoder analysis technique helped to simplify the complex nature of 3D spine models, while preserving the intrinsic properties that are typically measured with explicit parameters derived from the 3D reconstruction. PMID- 26851953 TI - Are non-invasive interventions effective for the management of headaches associated with neck pain? An update of the Bone and Joint Decade Task Force on Neck Pain and Its Associated Disorders by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. AB - PURPOSE: To update findings of the 2000-2010 Bone and Joint Decade Task Force on Neck Pain and its Associated Disorders and evaluate the effectiveness of non invasive and non-pharmacological interventions for the management of patients with headaches associated with neck pain (i.e., tension-type, cervicogenic, or whiplash-related headaches). METHODS: We searched five databases from 1990 to 2015 for randomized controlled trials (RCTs), cohort studies, and case-control studies comparing non-invasive interventions with other interventions, placebo/sham, or no interventions. Random pairs of independent reviewers critically appraised eligible studies using the Scottish Intercollegiate Guidelines Network criteria to determine scientific admissibility. Studies with a low risk of bias were synthesized following best evidence synthesis principles. RESULTS: We screened 17,236 citations, 15 studies were relevant, and 10 had a low risk of bias. The evidence suggests that episodic tension-type headaches should be managed with low load endurance craniocervical and cervicoscapular exercises. Patients with chronic tension-type headaches may also benefit from low load endurance craniocervical and cervicoscapular exercises; relaxation training with stress coping therapy; or multimodal care that includes spinal mobilization, craniocervical exercises, and postural correction. For cervicogenic headaches, low load endurance craniocervical and cervicoscapular exercises; or manual therapy (manipulation with or without mobilization) to the cervical and thoracic spine may also be helpful. CONCLUSIONS: The management of headaches associated with neck pain should include exercise. Patients who suffer from chronic tension type headaches may also benefit from relaxation training with stress coping therapy or multimodal care. Patients with cervicogenic headache may also benefit from a course of manual therapy. PMID- 26851956 TI - The global eradication of peste des petits ruminants (PPR) within 15 years--is this a pipe dream? AB - Gordon Scott did much to inspire the eradication of rinderpest, probably the most outstanding veterinary achievement of the twentieth century, and one currently inspiring is the proposed eradication of peste des petits ruminants (PPR), a disease of sheep and goats caused by a closely related Morbillivirus. The evolution and geographic spread of PPR along with its epidemiological characteristics are discussed and related to ways in which its spread can be reduced through the provision of diagnostic aids to sanitary livestock movement at local level. Taking a historical look at rinderpest eradication, it was shown that much could be achieved using a legislation-backed zoosanitary approach or, once developed, the build up of herd immunities in isolated populations. As the final cap to this (circa), two hundred-year-long process, major national and internationally funded vaccination programmes falling within the informal coordinatorship of the OIE and FAO showed that final eradication could be achieved with remarkable rapidity if the seat of infection was known and if appropriate national and international interventions were aimed at ending virus transmission. Were such international cooperation to be forthcoming once more, the understanding, tools and experiences now on offer suggest that PPR could be controlled and eradicated far more rapidly than rinderpest. PMID- 26851955 TI - Predicted structure of MIF/CD74 and RTL1000/CD74 complexes. AB - Macrophage migration inhibitory factor (MIF) is a key cytokine in autoimmune and inflammatory diseases that attracts and then retains activated immune cells from the periphery to the tissues. MIF exists as a homotrimer and its effects are mediated through its primary receptor, CD74 (the class II invariant chain that exhibits a highly structured trimerization domain), present on class II expressing cells. Although a number of binding residues have been identified between MIF and CD74 trimers, their spatial orientation has not been established. Using a docking program in silico, we have modeled binding interactions between CD74 and MIF as well as CD74 and a competitive MIF inhibitor, RTL1000, a partial MHC class II construct that is currently in clinical trials for multiple sclerosis. These analyses revealed 3 binding sites on the MIF trimer that each were predicted to bind one CD74 trimer through interactions with two distinct 5 amino acid determinants. Surprisingly, predicted binding of one CD74 trimer to a single RTL1000 antagonist utilized the same two 5 residue determinants, providing strong suggestive evidence in support of the MIF binding regions on CD74. Taken together, our structural modeling predicts a new MIF(CD74)3 dodecamer that may provide the basis for increased MIF potency and the requirement for ~3-fold excess RTL1000 to achieve full antagonism. PMID- 26851957 TI - UCA1 overexpression predicts clinical outcome of patients with ovarian cancer receiving adjuvant chemotherapy. AB - PURPOSE: Urothelial carcinoma associated 1 (UCA1) functions as an oncogene, which promotes cancer cell proliferation, invasion, and metastasis, and is responsible for drug resistance. This study aimed to determine the expression level of UCA1 in ovarian cancer and to further investigate its clinical significance. METHODS: The expression levels of UCA1 in ovarian cancer and normal ovaries were determined by quantitative real-time PCR. The relationship between UCA1 expression and clinical features and the prognostic value of UCA1 for overall survival were examined. RESULTS: UCA1 expression in ovarian cancer tissues was significantly upregulated compared with normal ovarian tissues. High UCA1 expression was related to lymph node metastasis, FIGO stage, and response to chemotherapy. Kaplan-Meier analysis demonstrated that high UCA1 expression was associated with poorer overall survival in patients with ovarian cancer. Cox proportional hazards analysis showed that high UCA1 expression was an independent prognostic marker of poor outcome. This effect remained significant in the further stratification analysis. CONCLUSIONS: Our findings provided the first evidence that UCA1 may serve as an indicator of response to chemotherapy and prognosis of ovarian cancer. UCA1 may play an important role in the progression of ovarian cancer. PMID- 26851958 TI - Development and Reproduction of Brethesiella cf. abnormicornis (Girault) (Hymenoptera: Encyrtidae), a Parasitoid of the Colombian Fluted Scale, Crypticerya multicicatrices Kondo & Unruh (Hemiptera: Monophlebidae). AB - Studies on the development and reproduction of Brethesiella cf. abnormicornis (Girault) (Hymenoptera: Encyrtidae), a parasitoid of the Colombian fluted scale, Crypticerya multicicatrices Kondo & Unruh (Hemiptera: Monophlebidae), were conducted under laboratory conditions. The duration of the life cycle, adult longevity, fecundity, and population parameters were determined. The parasitoid takes about 29 d to complete a single generation (from egg to adult). In addition, population parameters show that one female wasp is replaced by nearly 32 females, with a female-to-male sex ratio of 2:1. Population parameters estimated in this study can be considered baseline information for a mass-rearing protocol. This is the first detailed study of the biology of a species of Brethesiella, where the duration of all larval stages of the parasitoid is determined, being an important contribution for further biological studies of endoparasitoids. PMID- 26851959 TI - Clinical Values of Studying Kidney Elasticity with Virtual Touch Quantification in Gestational Hypertension Patients. AB - BACKGROUND The aim of this study was to investigate the differences in shear wave velocity (SWV) in renal cortex, renal medulla, and renal sinuses between gestational hypertension and normal pregnant women. MATERIAL AND METHODS Ninety patients with gestational hypertension and 30 women with normal pregnancy were enrolled in this study. Kidney biopsy was performed within 6 weeks to 3 months postpartum to determine the pathological nature of renal injury. According to the classification criteria for gestational hypertension, the patients were divided into 3 groups. Gestational hypertension only patients were classified as Group A; patients with mild preeclampsia as group B; patients with severe preeclampsia as group C; normal pregnant women as a control group. Virtual Touch Quantification technique was used to measure renal shear wave velocity; blood pressure, urine analysis, and renal function were also tested. RESULTS There was no difference in renal function between patients in group A and the control group (p>0.05), but there was a significant difference in renal function among patients in group A, B, and C, and there was a significant difference in renal function between patients in group B and C versus control (p<0.05 for all comparisons). There was also a significant difference in SWV values of the renal cortex, renal medulla, and renal sinus between patients in group A, B, and C versus control group (p<0.05). CONCLUSIONS The SWV values of the renal cortex, renal medulla, and renal sinus in patients with gestational hypertension were smaller than those of normal pregnant women, and the more severe the kidney injury, the smaller the SWV value. PMID- 26851960 TI - Doctors as street-level bureaucrats in a rural hospital in South Africa. AB - INTRODUCTION: In the perspectives of implementation of policy, the top-down and bottom-up perspectives of policy-making dominate the discourse. However, service delivery and therefore the experience of the policy by the citizen ultimately depend on the civil servant at the front line to implement the policy. Lipsky named this street-level bureaucracy, which has been used to understand professionals working in the public sector throughout the world. The public sector in South Africa has undergone a number of changes in the transition to a democratic state, post 1994. This needs to be understood in public administration developments throughout the world. At the time of the study, the public sector was characterized by considerable inefficiencies and system failures as well as inequitable distribution of resources. The context of the study was a rural hospital serving a population of approximately 150 000. RESULTS: An insider ethnography over a period of 13 months explored the challenges of being a professional within the public sector in a rural hospital in South Africa. Data collection included participant observation, field notes of events and meetings, and documentation review supplemented with in-depth interviews of doctors working at a rural hospital. Street-level bureaucracy was used as a framework to understand the challenges of being a professional and civil servant in the public sector. RESULTS: The context of a resource-constrained setting was seen as a major limitation to delivering a quality service. Yet considerable evidence pointed to doctors (both individually and collectively) being active in managing the services in the context and aiming to achieve optimal health service coverage for the population. In the daily routine of the work, doctors often advocated for patients and went beyond the narrow definitions of the guidelines. They compensated for failing systems, beyond a local interpretation of policy. However, doctors also at times used their discretion negatively, to avoid work or to contribute to the inefficiencies of healthcare delivery. CONCLUSIONS: While appearing to be in conflict, the merging of the roles of the health professional and the bureaucrat is required to be able to function effectively within the healthcare system. Being a doctor and being a civil servant are synergistic in daily work, and as a result it is difficult to neatly differentiate professional and civil servant roles in decision-making. It is in the discretion of both roles that considerable flexibility within the roles is possible. Such freedom to act is critical for being able to find local solutions and thereby improve healthcare services. The findings resonate strongly with studies from other parts of the world and offer a window into making sense of the local decision making of doctors. Street-level bureaucracy remains an important lens to view the work of healthcare professionals in the public sector. In the tension between the top down policy-making and the bottom-up pressure, street-level bureaucracy acts as an important terrain for improving the implementation of services and therefore advocacy and health system improvement. PMID- 26851961 TI - Role of Vorapaxar After Coronary Revascularization. AB - We aim to evaluate the potential benefit and risk of addition of vorapaxar to standard medical therapy in patients who underwent coronary revascularization with either percutaneous coronary revascularization or coronary artery bypass graft surgery. We searched PubMed, EMBASE, the Cochrane Central Register of Controlled trials, and the clinical trial registry maintained at clinicaltrials.gov for randomized control trials evaluating the safety and efficacy of vorapaxar in patients who underwent coronary revascularization procedures with either percutaneous coronary revascularization or coronary artery bypass graft surgery. Event rates were compared using a Forest plot of relative risk using a random-effects model. The 5 studies (n = 24,025) that met all criteria were included in the final analysis. After coronary revascularization procedures, addition of vorapaxar to standard medical therapy was associated with reduction in the risk of myocardial infarction (MI; risk ratio 0.83 [0.75 to 0.92]) and ischemic stroke (0.011 [0.007 to 0.016]); however, it also resulted in significant increase risk of hemorrhagic stroke (1.57 [1.01 to 2.44]) and Thrombolysis In Myocardial Infarction major and minor bleeds (1.36 [1.07 to 1.70]). There was no significant difference in the risk of cardiovascular mortality (0.90 [0.73 to 1.09]), repeat revascularization (0.78 [0.23 to 2.70]), and stent thrombosis (0.95 [0.62 to 1.45]) in the vorapaxar and control groups. In conclusion, after coronary revascularization procedures, addition of vorapaxar to standard medical therapy was associated with reduction in the risk of MI and ischemic stroke and increase in risk of hemorrhagic stroke and Thrombolysis In Myocardial Infarction major and minor bleeds. PMID- 26851962 TI - Comparison of Long-Term Mortality for Cardiac Diseases in Patients With Versus Without Diabetes Mellitus. AB - Diabetes mellitus confers the highest mortality risk in primary and secondary cardiovascular prevention, but long-term prognosis differences between different forms of cardiovascular disease have not been assessed. We hypothesized that acute heart failure (HF) could have poorer outcomes than acute coronary heart disease (CHD) in patients with diabetes. We performed a prospective study of all consecutive patients admitted in a single year. Patients were categorized according to main cardiologic diagnosis: acute HF, acute CHD, rhythm disorders, or noncardiac disease. A total of 1,293 patients were included, 31.8% had diabetes and had higher mean age, more risk factors, previous cardiovascular disease, and co-morbidities. Hospital mortality (5.6% vs 1.7%; p <0.01) was higher in patients with diabetes. During follow-up (median 58.0 months; interquartile range 31.0 to 60.0), diabetic patients had higher cardiovascular mortality (27.2% vs 9.6%; p <0.01) and all-cause mortality (35.8% vs 14.5%; p <0.01); cardiovascular disease accounted for 75% of deaths. According to discharge diagnosis, patients with diabetes only had higher mortality rates in the subgroup of acute CHD. Acute HF was the diagnosis with higher cardiovascular (36.9%) and all-cause mortality (44.1%), followed by acute CHD (16.8% and 24.4%) and rhythm disorders (5.8% and 8.8%). Multivariate analysis identified an independent association with higher long-term mortality of acute HF and acute CHD in patients with and without diabetes. In conclusion, 1/3 of cardiology-admitted patients have diabetes and have poorer long-term prognosis, especially when discharged with the diagnosis of acute HF or acute CHD. PMID- 26851963 TI - Superficial circumflex iliac artery perforator flap for tongue reconstruction. AB - OBJECTIVES: With microvascular reconstruction, different perforator flaps have been introduced for the treatment of head and neck defects. In light of this, the superficial circumflex iliac artery perforator (SCIP) flap was assessed for reconstruction after partial and hemiglossectomy. STUDY DESIGN: A total number of nine patients who received SCIP flap reconstruction for tongue defects were included in this study. Details on clinical features were collected, and postoperative functions and esthetic results were analyzed. RESULTS: All the SCIP flaps survived, and postoperative speech and swallowing functions were generally found to be acceptable during follow-up. In addition, subjective questionnaire appraisals from patients were favorable. CONCLUSION: The SCIP flap may present a good alternative for reconstruction of partial or hemiglossectomy defects. PMID- 26851964 TI - Characterizing the affective responses to an acute bout of moderate-intensity exercise among outpatients with schizophrenia. AB - In addition to offering many physical health benefits, exercise may help improve mental health among individuals with schizophrenia through regulating affect. Therefore, the purpose of this study is to characterize affective responses experienced before, during and after a 10-min bout of exercise versus passive sitting among individuals with schizophrenia. A randomized crossover design compared affect related to feelings of pleasure and arousal at baseline, 6-min into the task, immediately post-task, and 10min post-task to sitting. Thirty participants enroled in the study; 28 participants completed the study. Separate mixed model analyses of variance were conducted for pleasure and arousal, with test order as the between-subject factor, and time and task as within-subject factors. For pleasure, a significant main effect for time and a time x task interaction effect emerged. Post-hoc Bonferroni corrected t-tests (alpha=.0125) revealed significant differences between pleasure at baseline and both immediately post-task and 10min post-task. No other main effects or interactions emerged. Individuals with schizophrenia derive acute feelings of pleasure from exercise. Thus, exercise may provide a method of regulating affect to improve mental health. Future studies should examine the links between affective responses to health behaviours such as long-term adherence to exercise within this population. PMID- 26851965 TI - Time for a randomised clinical trial evaluating breast conserving surgery compared to mastectomy in ipsilateral mutlifocal breast cancer (MFBC)? PMID- 26851966 TI - Indoor microbial communities: Influence on asthma severity in atopic and nonatopic children. AB - BACKGROUND: Allergic and nonallergic asthma severity in children can be affected by microbial exposures. OBJECTIVE: We sought to examine associations between exposures to household microbes and childhood asthma severity stratified by atopic status. METHODS: Participants (n = 196) were selected from a cohort of asthmatic children in Connecticut and Massachusetts. Children were grouped according to asthma severity (mild with no or minimal symptoms and medication or moderate to severe persistent) and atopic status (determined by serum IgE levels). Microbial community structure and concentrations in house dust were determined by using next-generation DNA sequencing and quantitative PCR. Logistic regression was used to explore associations between asthma severity and exposure metrics, including richness, taxa identification and quantification, community composition, and concentration of total fungi and bacteria. RESULTS: Among all children, increased asthma severity was significantly associated with an increased concentration of summed allergenic fungal species, high total fungal concentrations, and high bacterial richness by using logistic regression in addition to microbial community composition by using the distance comparison t test. Asthma severity in atopic children was associated with fungal community composition (P = .001). By using logistic regression, asthma severity in nonatopic children was associated with total fungal concentration (odds ratio, 2.40; 95% CI, 1.06-5.44). The fungal genus Volutella was associated with increased asthma severity in atopic children (P = .0001, q = 0.04). The yeast genera Kondoa might be protective; Cryptococcus species might also affect asthma severity. CONCLUSION: Asthma severity among this cohort of children was associated with microbial exposure, and associations differed based on atopic status. PMID- 26851967 TI - Rapid recruitment of CD14(+) monocytes in experimentally induced allergic rhinitis in human subjects. AB - BACKGROUND: Activated TH2 cells and eosinophils are hallmarks of the allergic inflammation seen in patients with allergic rhinitis (AR). However, which cells activate and attract T cells and eosinophils to the inflammatory lesion has not been determined. OBJECTIVE: We wanted to assess the role of mucosal mononuclear phagocytes, consisting of monocytes, macrophages, and dendritic cells, in the local allergic inflammatory reaction. METHODS: Patients with AR and nonatopic control subjects were challenged with pollen extract, and nasal symptoms were recorded. Mucosal biopsy specimens obtained at different time points before and after challenge were used for immunostaining in situ and flow cytometric cell sorting. Sorted mononuclear phagocytes were subjected to RNA extraction and gene expression profiling. RESULTS: In an in vivo model of AR, we found that CD14(+) monocytes were recruited to the nasal mucosa within hours after local allergen challenge, whereas conventional dendritic cells accumulated after several days of continued provocation. Transcriptomic profiling of mucosal mononuclear phagocytes sorted after 1 week of continued allergen challenge showed an activated phenotype at least partially driven by IL-4 signaling, IL-13 signaling, or both. Importantly, gene expression of several TH2-related chemokines was significantly upregulated by the mononuclear phagocyte population concomitant with an increased recruitment of CD4(+) T cells and eosinophils. CONCLUSION: Our findings suggest that the mononuclear phagocyte population is directly involved in the production of proinflammatory chemokines that attract other immune cells. Rapid recruitment of CD14(+) monocytes to the challenged site indicates that these proinflammatory mononuclear phagocytes have a central role in orchestrating local allergic inflammation. PMID- 26851969 TI - Poststroke Physical Activity Levels No Higher in Rehabilitation than in the Acute Hospital. AB - BACKGROUND: Returning to physical activity is a common goal for stroke survivors undergoing rehabilitation, and higher levels of activity have been linked to better gait and greater independence in activities of daily living. Our aim was to determine if inpatient rehabilitation settings promoted higher levels of physical activity in stroke survivors than an acute stroke unit setting. METHODS: Stroke survivors were recruited from the inpatient rehabilitation wards of 4 different hospitals in southern Sweden and from the acute stroke unit at Karolinska University Hospital in Stockholm. Participants were observed for 1 minute every 10 minutes from 8:00 a.m. to 5:00 p.m. At each observation, the person's highest level of physical activity, location, and other people present were recorded. RESULTS: We collected data from 190 stroke survivors (104 rehabilitation, 86 acute). Contrary to our hypothesis, there was no significant difference between the groups in the amount of time spent in moderate-to-high physical activity (rehabilitation median 24%, acute median 23%; adjusted P = .74). Compared to those in the acute setting, participants in the rehabilitation setting spent less time lying in bed, more time sitting supported out of bed, less time in their bedroom, and more time with a therapist (all adjusted P < .001). CONCLUSION: In the context of stroke, the inpatient rehabilitation environment does not appear to promote higher levels of physical activity than the acute hospital environment. PMID- 26851968 TI - Multidimensional endotyping in patients with severe asthma reveals inflammatory heterogeneity in matrix metalloproteinases and chitinase 3-like protein 1. AB - BACKGROUND: Disease heterogeneity in patients with severe asthma and its relationship to inflammatory mechanisms remain poorly understood. OBJECTIVE: We aimed to identify and replicate clinicopathologic endotypes based on analysis of blood and sputum parameters in asthmatic patients. METHODS: One hundred ninety four asthmatic patients and 21 control subjects recruited from 2 separate centers underwent detailed clinical assessment, sputum induction, and phlebotomy. One hundred three clinical, physiologic, and inflammatory parameters were analyzed by using topological data analysis and Bayesian network analysis. RESULTS: Severe asthma was associated with anxiety and depression, obesity, sinonasal symptoms, decreased quality of life, and inflammatory changes, including increased sputum chitinase 3-like protein 1 (YKL-40) and matrix metalloproteinase (MMP) 1, 3, 8, and 12 levels. Topological data analysis identified 6 clinicopathobiologic clusters replicated in both geographic cohorts: young, mild paucigranulocytic; older, sinonasal disease; obese, high MMP levels; steroid resistant TH2 mediated, eosinophilic; mixed granulocytic with severe obstruction; and neutrophilic, low periostin levels, severe obstruction. Sputum IL-5 levels were increased in patients with severe particularly eosinophilic forms, whereas IL-13 was suppressed and IL-17 levels did not differ between clusters. Bayesian network analysis separated clinical features from intricately connected inflammatory pathways. YKL-40 levels strongly correlated with neutrophilic asthma and levels of myeloperoxidase, IL-8, IL-6, and IL-6 soluble receptor. MMP1, MMP3, MMP8, and MMP12 levels were associated with severe asthma and were correlated positively with sputum IL-5 levels but negatively with IL-13 levels. CONCLUSION: In 2 distinct cohorts we have identified and replicated 6 clinicopathobiologic clusters based on blood and induced sputum measures. Our data underline a disconnect between clinical features and underlying inflammation, suggest IL-5 production is relatively steroid insensitive, and highlight the expression of YKL 40 in patients with neutrophilic inflammation and the expression of MMPs in patients with severe asthma. PMID- 26851970 TI - Intravenous Thrombolysis Facilitates Successful Recanalization with Stent Retriever Mechanical Thrombectomy in Middle Cerebral Artery Occlusions. AB - AIM: Several factors influence the outcome after acute ischemic stroke secondary to proximal occlusions of cerebral vessels. Among others, noneligibility for intravenous thrombolysis (IVT) and incomplete revascularization have been identified as predictors of unfavorable outcome. The aim of this study was to investigate whether concomitant IVT influences the revascularization efficacy in mechanical thrombectomy (MT). METHODS: This study conducted a retrospective analysis of all consecutive patients presenting with an anterior circulation stroke due to large-artery occlusion with imaging evidence who were treated with MT between July 2012 and December 2013 at 2 high-volume stroke centers. Imaging data were regraded and re-evaluated according to the modified Treatment in Cerebral Ischemia scale and its respective vessel occlusion site definitions. Clinical end points included National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale; imaging and procedural measures were technical end points. RESULTS: We identified 93 patients who presented with an occlusion of the middle cerebral artery (MCA): of these patients, 66 (71%) received IVT. We did not find statistically significant differences in the baseline NIHSS score, time from symptom onset to groin puncture, and age when comparing the IVT group with the non-IVT group. The rate of successful recanalizations (modified Treatment in Cerebral Ischemia score >= 2b) was significantly higher in patients with MCA occlusion and concomitant IVT (P = .01). Stepwise logistic regression identified IVT and thrombus length as predictive factors for successful mechanical recanalization (P = .004, P = .002). CONCLUSION: IVT and thrombus length are predictive factors for a successful recanalization in MT for acute ischemic stroke with underlying MCA occlusion. PMID- 26851971 TI - Epigallocatechin Gallate Extends the Therapeutic Window of Recombinant Tissue Plasminogen Activator Treatment in Ischemic Rats. AB - BACKGROUND: Ischemic stroke is the leading cause of death and disability worldwide. To date, recombinant tissue plasminogen activator (rt-PA) remains the only safe and effective pharmaceutical treatment for brain ischemia, but delayed rt-PA administration leads to hyperperfusion, which severely limits its clinical efficacy. METHODS: In this study, we investigated the effect of epigallocatechin gallate (EGCG) in extending the therapeutic window of rt-PA using a rat middle cerebral artery occlusion (MCAO) model. RESULTS: Simultaneous treatment of EGCG and rt-PA significantly recovered the neurobehavioral deficit, when administered even 4 hours after MCAO. Pathological examinations on the ischemic brain samples revealed that EGCG significantly alleviated the common side effects of delayed rt PA treatment, including brain infarction, cerebral edema, and blood-brain barrier disruption. We further found that EGCG exerted its protective functions against delayed rt-PA through upregulation of plasminogen activator inhibitor-1, as well as downregulation of matrix metalloproteinases. CONCLUSION: Our study has demonstrated for the first time in vivo results supporting the potential of EGCG to be coadministered with rt-PA, to extend its therapeutic window in treating acute brain ischemia. PMID- 26851972 TI - Intracranial Atherosclerosis and Poststroke Depression in Chinese Patients with Ischemic Stroke. AB - BACKGROUND: Intracranial atherosclerosis (ICAS) is a common etiology of ischemic stroke in Chinese patients, probably leading to regional hypoperfusion in the brain. The purpose of this prospective study was to investigate the association between ICAS and poststroke depression in Chinese patients with ischemic stroke. METHODS: During the study period, a total of 569 patients aged between 40 and 80 years with acute ischemic stroke were consecutively admitted and screened. Patients with a National Institutes of Health Stroke Scale (NIHSS) total score of 15 or higher, with severe cognitive impairment, or with a history of depression before stroke were excluded. Two hundred seven patients with ischemic stroke were consecutively recruited in the study. Depressive symptoms were assessed in the acute stage and 3 months after stroke. Poststroke depression was defined as a score of 8 or higher in the 24-item Hamilton Depression Rating Scale. The evaluation of the magnetic resonance imaging scans focused on infarctions, white matter lesions, brain atrophy, and ICAS. RESULTS: In the acute stage of stroke, logistic regression revealed that female sex, NIHSS score at admission, prestroke insomnia, and ICAS were significant predictors of poststroke depression. At 3 months after stroke, prestroke insomnia, the Mini-Mental State Examination score and ICAS were significant predictors of poststroke depression. CONCLUSIONS: ICAS may be a significant independent predictor of poststroke depression in Chinese patients with ischemic stroke. PMID- 26851973 TI - Measurement of Resistive Plantar Flexion Torque of the Ankle during Passive Stretch in Healthy Subjects and Patients with Poststroke Hemiplegia. AB - BACKGROUND: Quantification of increased muscle tone for patients with spasticity has been performed to date using various devices to replace the manual scales, such as the modified Ashworth scale or the Tardieu scale. We developed a device that could measure resistive plantar flexion (PF) torque of the ankle during passive dorsiflexion (DF) as an indicator of muscle tone of ankle plantar flexors. METHODS: The primary objective was to explore the test-retest intrarater reliability of a custom-built device. Participants were 11 healthy subjects (7 men, 4 women; mean age 47.0 years) and 22 patients with poststroke hemiplegia (11 hemorrhagic, 11 ischemic; 14 men, 8 women; mean age 57.2 years). The device was affixed to the ankle. Subjects were seated with knees either flexed or extended. The ankle was passively dorsiflexed from 20 degrees of PF to more than 10 degrees of DF at 5 degrees /second (slow stretch) or 90 degrees /second (fast stretch). Angle and torque were measured twice during the stretches. The intraclass correlation coefficients (ICCs) of torque at 10 degrees of DF (T10) in the 4 conditions-slow and fast stretches with knee flexed or extended-were calculated. RESULTS: The T10 ICCs of the 4 conditions were .95-.99 in both groups. The healthy subjects showed significantly higher T10 of knee extension than of knee flexion during slow and fast stretches. The patients showed increased velocity-dependent torque during fast stretches. CONCLUSIONS: Excellent reliability was observed. The device is suitable for measuring resistive PF torque during passive stretch in a flexed knee condition. PMID- 26851974 TI - Effects of rivastigmine on visual attention in subjects with amnestic mild cognitive impairment: A serial functional MRI activation pilot-study. AB - A pilot study to investigate the effects of rivastigmine on the brain activation pattern due to visual attention tasks in a group of amnestic Mild Cognitive Impaired patients (aMCI). The design was an initial three-month double blind period with a rivastigmine and placebo arms, followed by a nine-month open-label period. All patients underwent serial functional magnetic resonance imaging (fMRI) at baseline, and after three and six months of follow-up. Primary endpoint was the effect of rivastigmine on functional brain changes during visual attention (face and location matching) tasks. There were five in the rivastigmine arm and two in the placebo arm. The face matching task showed higher activation of visual areas after three months of treatment but no differences compared to baseline at six months. The location matching task showed a higher activation along the dorsal visual pathway at both three and six months follow ups. Treatment with rivastigmine demonstrates a significant effect on brain activation of the dorsal visual pathway during a location matching task in patients with aMCI. Our data support the potential use of task fMRI to map specific treatment effects of cholinergic drugs during prodromal stages of Alzheimer's disease (AD). PMID- 26851976 TI - Computed Tomography Imaging in Oncology. AB - Computed tomography (CT) imaging has become the mainstay of oncology, providing accurate tumor staging and follow-up imaging to monitor treatment response. Presurgical evaluation of tumors is becoming commonplace and guides surgeons as to the extent and whether complete tumor resection is possible. CT imaging plays a crucial role in radiotherapy treatment planning. CT imaging in oncology has become ubiquitous in veterinary medicine because of increased availability of this imaging modality. This article focuses on CT cancer staging in veterinary oncology, CT imaging for surgical planning, and advances in CT simulation for radiation therapy planning. PMID- 26851975 TI - Ultrasound Imaging of the Hepatobiliary System and Pancreas. AB - Ultrasound is an extremely valuable diagnostic modality for the diagnosis of hepatobiliary and pancreatic disease. Normal appearance and normal variations are important to understand to avoid misinterpretation. Although ultrasound can identify a lesion, cytology and histopathology are usually needed for a final diagnosis. PMID- 26851977 TI - Interventional Oncology. AB - The approach to the treatment of cancer in veterinary patients is constantly evolving. Whenever possible and practical, surgery is pursued because it provides the greatest opportunity for tumor control and may result in a cure. Other cancer treatments, such as chemotherapy and radiation therapy, are commonplace in veterinary medicine, and the data outlining treatment regimens are growing rapidly. An absence of treatment options for veterinary cancer patients, however, has historically existed for some tumors. Interventional oncology options have opened the door to the potential for better therapeutic response and improved patient quality of life. PMID- 26851978 TI - [Tuberculosis and immigration]. AB - The incidence of tuberculosis worldwide is declining. However, in Western countries this decline is slower due to the impact of immigration. Tuberculosis in the immigrant population is related to health status in the country of origin and with overcrowding and poverty conditions in the host country. Immigrants with tuberculosis are younger, have a higher prevalence of extrapulmonary forms, greater proportion of drug resistance and higher treatment default rates than those of natives. New molecular techniques not only reduce diagnostic delay time but also allow the rapid identification of resistances and improve knowledge of transmission patterns. It is necessary to implement measures to improve treatment compliance in this population group like facilitating access to health card, the use of fixed-dose combination drugs, the participation of cultural mediators and community health workers and gratuity of drugs. PMID- 26851979 TI - Alteration of cytokine profile following hemorrhagic shock. AB - Hemorrhage is one of the leading causes of death in patients with trauma. We recently demonstrated that resveratrol can improve cardiac function and prolong life following severe hemorrhagic injury (HI) in a rat model. The present work is focused on determining changes in NF-kappaB dependent gene expression in the heart and the systemic cytokine milieu following HI and the effect of resveratrol treatment. The results indicate an increase in phosphorylated NF-kappaB in the heart with a concomitant increase in the expression of NF-kappaB dependent genes following HI. There was also a significant increase of systemic cytokine levels, both pro and anti-inflammatory, following HI and resolution when treated with resveratrol. This study demonstrates the potential role NF-kappaB has in the physiological response to HI and the effectiveness of resveratrol in reducing immune activation. PMID- 26851980 TI - Pollution by metals and toxicity assessment using Caenorhabditis elegans in sediments from the Magdalena River, Colombia. AB - The Magdalena River is the most important river in Colombia, supplying over 70% of the population of fish and drinking water, and it also is the main river transportation way of the country. It receives effluents from multiple sources along its course such as contaminant agricultural and industrial discharges. To evaluate the toxicity profile of Magdalena River sediments through endpoints such as survival, locomotion, and growth, wild type strains of Caenorhabditis elegans were exposed to aqueous extracts of the sediments. To identify changes in gene expression, GFP transgenic strains were used as reporter genes. Physiological and biochemical data were correlated with metal concentration in the sediments, identifying patterns of toxicity along the course of the river. Levels of some metals such as Cd, Cu, and Ni were above TEC and PEC limits. Effects in survival, growth, and locomotion were observed in most of the samples, and changes in gene expression were evident in the genes mtl-2, sod-4, and gst-1 using fluorescence expression. Cadmium and lead were the metals which were primarily associated with sediment toxicity, and the sampling sites with the highest increased expression of stress response genes were Barrancabermeja and Girardot. However, the diverse nature of toxic profiles observed in C. elegans in the study area showed the pervasiveness of different types of discharges throughout the river system. PMID- 26851981 TI - Intestinal alterations in European sea bass Dicentrarchus labrax (Linnaeus, 1758) exposed to microplastics: Preliminary results. AB - This study investigates, for the first time, the intestinal responses of European sea bass Dicentrarchus labrax chronically exposed to microplastics through ingestion. Fish (n = 162) were fed with 3 different treatment diets for 90 days: control, native polyvinyl chloride (PVC) and polluted polyvinyl chloride (PVC) pellets. Intestines were fixed and processed for histological analysis using standard techniques. Histopathological alterations were examined using a score value (from 0 to 4). The distal part of intestine in all samples proved to be the most affected by pathological alterations, showing a gradual change varying from moderate to severe related to exposure times. The histological picture that characterizes both groups especially after 90 days of exposure, suggests that the intestinal functions can be in some cases totally compromised. The worst condition is increasingly evident in the distal intestine of fish fed with polluted PVC pellets respect to control groups (p < 0.05) to different exposure times. These first results underline the need to assess the impact of increasing microplastics pollution on the marine trophic web. PMID- 26851982 TI - Postictal generalized EEG suppression after generalized convulsive seizures: A double-edged sword. AB - OBJECTIVE: The aim of this study is to investigate the key facilitating factors for postictal generalized EEG suppression (PGES) in a large cohort of patients with generalized convulsive seizures (GCSs). METHODS: We retrospectively reviewed the data of consecutive patients who had GCSs in the epilepsy monitoring units of two epilepsy centers. Statistical analysis was performed to assess specific variables as potential risk factors for PGES. RESULTS: Among the 208 enrolled patients with 366 seizures, PGES was observed in 109 (51.9%) patients and 168 (45.9%) GCSs. The mean duration of PGES was 33.2 +/- 12.0 s (34 s, 3-70 s). PGES or severe PGES (>20 s) was associated with more severe postictal coma and temporal lobe epilepsy. Moreover, PGES was independently associated with a longer tonic duration, shorter total seizure duration, and lower habitual seizure frequency. CONCLUSIONS: PGES is strongly correlated not only with longer tonic duration, but also with shorter total seizure duration and lower habitual seizure frequency. SIGNIFICANCE: PGES may represent a switch-off inhibitory mechanism in seizure termination; moreover, it may indicate the efficacy of a long-lasting inhibitory network that suppresses GCS ictogenesis. PMID- 26851984 TI - Early market access for unauthorized drugs in Italy: The value-based price for reimbursement decisions. PMID- 26851983 TI - First data from Latvian chronic thromboembolic pulmonary hypertension registry. PMID- 26851985 TI - Current topics in HIV pathogenesis, part 2: Inflammation drives a Warburg-like effect on the metabolism of HIV-infected subjects. AB - HIV-1 infection leads to a depletion of CD4 T-cells associated with a persistent immune inflammation and changes in cellular metabolism. Most effort of managing HIV infection with combination of antiretroviral therapies (ART) has been focused on CD4 T-cell recovery, while control of persistent immune inflammation and metabolism were relatively underappreciated in the past. Recent discoveries on the interplay between innate immunity, inflammation (especially the inflammasome) and metabolic changes in the context of cancer and autoimmunity provide an emerging field for chronic viral infections including HIV-1. In a previous review, we described the deregulated metabolism contributing to immune dysfunctions such as alteration of memory T-cell responses, mucosal protection, and dendritic cell-related antigen presentation. Here, we summarize the latest knowledge on the detrimental influence of long-lasting inflammation and inflammasome activation induced by HIV-1, gut dysbiosis, and bacterial translocation, on metabolism during the course of viral infection. We also report on the inability of ART to fully counteract inflammation, resulting in partial metabolic improvement and leading to an insufficient decrease in the risk of non AIDS events. Further advances in our understanding of the relationship between inflammation, altered metabolism, and long-term ART is warranted. Additionally, there is a critical need for developing new strategies to regulate the pro inflammatory signals to enhance cellular metabolism and immune functions in order to improve the quality of life of individuals living with HIV-1. PMID- 26851986 TI - A systematic review of the motivations for the non-medical use of prescription drugs in young adults. AB - BACKGROUND: Young adults (18-25) are most at-risk for the non-medical use of prescription drugs (NMUPD). Understanding this population's motivations for use can help inform efforts to reduce NMUPD. Therefore, this systematic review synthesizes the findings from research on young adults' motivations to engage in NMUPD. METHODS: Based on PRISMA guidelines, relevant databases were systematically searched for articles that assessed the motivations for NMUPD in young adults and college-aged students. Search strings included a range of prescription drug classes and terms to ensure an exhaustive review. RESULTS: The search resulted in identifying 353 potential articles after duplicates were removed, and 37 articles were included in the final qualitative synthesis. Of the final articles, the majority investigated the non-medical use of prescription stimulants in U.S. student populations cross-sectionally. Seven studies, either exclusively or in combination with other medications, researched prescription opioids, and five investigated central nervous system depressants. Only one study investigated motivations over time. CONCLUSION: There are many ways in which the current literature can be expanded, including researching other populations and focusing on prescriptions other than stimulants. Using the medications for their prescribed properties and known side effects emerged as a consistent theme. It was also fairly common for young adults to report recreational motives. Issues with measurement and definitions of key terms (e.g., non-medical) would benefit from consistency in future work. Research on motivations should continue and be incorporated into the larger drug use context, as well as existing prevention and intervention strategies. PMID- 26851988 TI - Genomic stability during cellular reprogramming: Mission impossible? AB - The generation of induced pluripotent stem cells (iPSCs) from adult somatic cells is one of the most exciting discoveries in recent biomedical research. It holds tremendous potential in drug discovery and regenerative medicine. However, a series of reports highlighting genomic instability in iPSCs raises concerns about their clinical application. Although the mechanisms cause genomic instability during cellular reprogramming are largely unknown, several potential sources have been suggested. This review summarizes current knowledge on this active research field and discusses the latest efforts to alleviate the genomic insults during cellular reprogramming to generate iPSCs with enhanced quality and safety. PMID- 26851987 TI - Comparison of methods to assess psychiatric medication adherence in methadone maintained patients with co-occurring psychiatric disorder. AB - BACKGROUND: Adherence with psychiatric medication is a critical issue that has serious individual and public health implications. This is a secondary analysis of a large-scale clinical treatment trial of co-occurring substance use and psychiatric disorder. METHOD: Participants (n=153) who received a clinically indicated psychiatric medication >=30 days during the 12-month study and provided corresponding data from Medication Event Monitoring System (MEMS) and Morisky Medication Taking Adherence Scale (MMAS) self-report adherence ratings were included in the analyses. Accuracy in MEMS caps openings was customized to each participant's unique required dosing schedule. RESULTS: Consistent with expectations, MEMS-based adherence declined slowly over time, though MMAS scores of forgetting medication remained high and did not change over the 12-month study. MEMS caps openings were not significantly impacted by any baseline or treatment level variables, whereas MMAS scores were significantly associated with younger age and presence of an Axis I disorder and antisocial personality disorder, or any cluster B diagnoses. CONCLUSIONS: Results suggest that MEMS caps may be a more objective method for monitoring adherence in patients with co occurring substance use and psychiatric disorder relative to the MMAS self report. Participants in this study were able to successfully use the MEMS caps for a 12-month period with <1% lost or broken caps, suggesting this comorbid population is able to use the MEMS successfully. Ultimately, these data suggest that an objective method for monitoring adherence in this treatment population yield more accurate outcomes relative to self-report. PMID- 26851989 TI - Adenoid Cystic Carcinoma of Accessory Parotid Gland: A Case Report. AB - The accessory parotid gland is salivary gland tissue separated from the main gland at a variable distance. This gland is histologically similar to the main gland, but has a higher incidence of malignant neoplasms than the main gland. Regarding the various malignant neoplasms, studies have shown higher incidences of mucoepidermoid carcinoma, with less than 2% being adenoid cystic carcinoma. We present a case of swelling in the midcheek region that, after clinical examination, was diagnosed as a case of neoplasm of the accessory parotid gland. On the basis of auxiliary investigations including intraoperative frozen section, it was concluded that it was adenoid cystic carcinoma, grade I, and after wide surgical resection, the tumor was removed without undergoing superficial parotidectomy. The patient received postoperative radiotherapy (RT) and was followed for 14 months without any recurrence or substantial facial asymmetry. PMID- 26851990 TI - The policy contribution of the German Health Economic Centres. PMID- 26851991 TI - A new proposal for priority setting in Norway: Open and fair. AB - Health systems worldwide struggle to meet increasing demands for health care, and Norway is no exception. This paper discusses the new, comprehensive framework for priority setting recently laid out by the third Norwegian Committee on Priority Setting in the Health Sector. The framework posits that priority setting should pursue the goal of "the greatest number of healthy life years for all, fairly distributed" and centres on three criteria: 1) The health-benefit criterion: The priority of an intervention increases with the expected health benefit (and other relevant welfare benefits) from the intervention; 2) The resource criterion: The priority of an intervention increases, the less resources it requires; and 3) The health-loss criterion: The priority of an intervention increases with the expected lifetime health loss of the beneficiary in the absence of such an intervention. Cost-effectiveness plays a central role in this framework, but only alongside the health-loss criterion which incorporates a special concern for the worse off and promotes fairness. In line with this, cost-effectiveness thresholds are differentiated according to health loss. Concrete implementation tools and open processes with user participation complement the three criteria. Informed by the proposal, the Ministry of Health and Care Services is preparing a report to the Parliament, with the aim of reaching political consensus on a new priority setting framework for Norway. PMID- 26851992 TI - New methodologies for measuring Brugada ECG patterns cannot differentiate the ECG pattern of Brugada syndrome from Brugada phenocopy. AB - BACKGROUND: Brugada phenocopies (BrP) are clinical entities characterized by ECG patterns that are identical to true Brugada syndrome (BrS), but are elicited by various clinical circumstances. A recent study demonstrated that the patterns of BrP and BrS are indistinguishable under the naked eye, thereby validating the concept that the patterns are identical. OBJECTIVE: The aim of our study was to determine whether recently developed ECG criteria would allow for discrimination between type-2 BrS ECG pattern and type-2 BrP ECG pattern. METHODS: Ten ECGs from confirmed BrS (aborted sudden death, transformation into type 1 upon sodium channel blocking test and/or ventricular arrhythmias, positive genetics) cases and 9 ECGs from confirmed BrP were included in the study. Surface 12-lead ECGs were scanned, saved in JPEG format for blind measurement of two values: (i) beta angle; and (ii) the base of the triangle. Cut-off values of >=58 degrees for the beta-angle and >=4mm for the base of the triangle were used to determine the BrS ECG pattern. RESULTS: Mean values for the beta-angle in leads V1 and V2 were 66.7+/-25.5 and 55.4+/-28.1 for BrS and 54.1+/-26.5 and 43.1+/-16.1 for BrP respectively (p=NS). Mean values for the base of the triangle in V1 and V2 were 7.5+/-3.9 and 5.7+/-3.9 for BrS and 5.6+/-3.2 and 4.7+/-2.7 for BrP respectively (p=NS). The beta-angle had a sensitivity of 60%, specificity of 78% (LR+ 2.7, LR- 0.5). The base of the triangle had a sensitivity of 80%, specificity of 40% (LR+ 1.4, LR- 0.5). CONCLUSIONS: New ECG criteria presented relatively low sensitivity and specificity, positive and negative predictive values to discriminate between BrS and BrP ECG patterns, providing further evidence that the two patterns are identical. PMID- 26851993 TI - Evaluation of Plasma Melatonin Levels in Children With Afebrile and Febrile Seizures. AB - BACKGROUND: Melatonin modulates central nervous system neuronal activity. We compared the melatonin levels of patients with febrile and afebrile seizures during and after seizure with those of healthy controls. METHODS: We enrolled 59 individuals with afebrile and febrile seizures (mean age, 6.09 +/- 4.46 years) and 28 age-, sex-, and weight-matched healthy children. Melatonin levels were measured near the time of a seizure (0 to 1 hour) and at 12 and 24 hours post seizure, and control melatonin levels were measured from a single venous blood sample. RESULTS: Plasma melatonin levels increased during seizures in the study group (P < 0.001). Post-seizure plasma melatonin levels were significantly lower in the study group than in the control group (P < 0.05). Plasma melatonin levels did not differ between patients with afebrile seizures who had and had not used antiepileptic drugs. Daytime (8 AM to 8 PM) and nighttime (8 PM to 8 AM) post seizure melatonin levels were not significantly different. CONCLUSIONS: Melatonin levels were lower in pediatric patients prone to seizures than in healthy children and increased during seizures. Further research is needed to test the role of melatonin in the pathophysiology and treatment of epilepsy. PMID- 26851994 TI - The concept of prehabilitation: What the surgeon needs to know? AB - Despite advances in surgical techniques, anesthesia and perioperative care, which became safer and accessible to a higher proportion of high-risk patients, major surgery remains morbid with a lot of patients not recovering their previous capacity. Indeed surgery is a physiological stress and decreases functional capacity in the postoperative period. A "prehabilitation" program should increase functional capacity in anticipation of an upcoming stress. It should occur after the surgical consultation and before surgery, and is based on three components: physical care, nutritional support and psychological support, during 6 to 8 weeks. The aims of prehabilitation are to improve both nutritional status and pre and postoperative fitness, and to reduce postoperative complications. Prehabilitation demonstrated benefit on postoperative complications in cardiovascular surgery but its benefit in digestive surgery is still unclear with contradictory results. The aim of this review was to summarize results of prehabilitation on the pre- and postoperative period and to determine its possible future in digestive surgery. PMID- 26851995 TI - Directivity patterns of laser-generated sound in solids: Effects of optical and thermal parameters. AB - In the present paper, directivity patterns of laser-generated sound in solids are investigated theoretically. Two main approaches to the calculation of directivity patterns of laser-generated sound are discussed for the most important case of thermo-optical regime of generation. The first approach, which is widely used in practice, is based on the simple modelling of the equivalent thermo-optical source as a mechanical dipole comprising two horizontal forces applied to the surface in opposite directions. The second approach is based on the rigorous theory that takes into account all acoustical, optical and thermal parameters of a solid material and all geometrical and physical parameters of a laser beam. Directivity patterns of laser-generated bulk longitudinal and shear elastic waves, as well as the amplitudes of generated Rayleigh surface waves, are calculated for different values of physical and geometrical parameters and compared with the directivity patterns calculated in case of dipole-source representation. It is demonstrated that the simple approach using a dipole-source representation of laser-generated sound is rather limited, especially for description of generated longitudinal acoustic waves. A practical criterion is established to define the conditions under which the dipole-source representation gives predictions with acceptable errors. It is shown that, for radiation in the normal direction to the surface, the amplitudes of longitudinal waves are especially sensitive to the values of thermal parameters and of the acoustic reflection coefficient from a free solid surface. A discussion is given on the possibility of using such a high sensitivity to the values of the reflection coefficient for investigation of surface properties of real solids. PMID- 26851997 TI - Reply by Authors. PMID- 26851996 TI - Editorial Comment. PMID- 26851998 TI - Editorial Comment. PMID- 26851999 TI - Editorial Comment. PMID- 26852000 TI - Editorial Comment. PMID- 26852001 TI - Graded changes in enamel component volumes resulted from a short tooth bleaching procedure. AB - AIM: To test the hypothesis that changes in enamel component volumes (mineral, organic, and water volumes, and permeability) are graded from outer to inner enamel after a short bleaching procedure. MATERIALS AND METHODS: Extracted unerupted human third molars had half of their crowns bleached (single bleaching session, 3 * 15 min), and tooth shade changes in bleached parts were analyzed with a spectrophotometer. Ground sections were prepared, component volumes and permeability were quantified at histological points located at varying distances from the enamel surface (n=10 points/location), representing conditions before and after bleaching. RESULTS: Tooth shade changes were significant (p<0.001; 95% CI=-1/-8; power=99%), and most of the enamel layer was unaffected after bleaching, except at the outer layers. Multiple analysis of covariances revealed that most of the variance of the change in enamel composition after bleaching was explained by the combination of the set of types of component volume (in decreasing order of relevance: mineral loss, organic gain, water gain, and decrease in permeability) with the set of distances from the enamel surface (graded from the enamel surface inward) (canonical R(2)=0.97; p<0.0001; power>99%). CONCLUSIONS: Changes in enamel composition after a short bleaching procedure followed a gradient within component volumes (mineral loss>organic gain>water gain>decrease in permeability) and decreased from the enamel surface inward. PMID- 26852002 TI - Cell differentiation and the multiple drug resistance phenotype in human erythroleukemic cells. AB - The gene expression of Oct-4, a transcription factor and hematopoietic stem cell marker, is higher in Lucena lines, which is MDR, and the gene Alox-5 has also been implicated in the differentiation of some cell lines. The aim of this study was to compare the response to PMA-induced differentiation in MDR and non-MDR cells. We observed the differentiation to megakaryocytes in the K562 cell line, which is non-MDR. The expression of Alox-5 and Nanog genes was downregulated and that of Mdr-1 was upregulated in K562 cells. The Lucena cell line contained a higher number of megakaryocytes than the non-MDR, but this number was not altered by PMA, as well as Mdr-1 gene expression. However, Alox-5 expression was downregulated. Alox-5, Mdr-1, Nanog, Oct-4 and Sox-2 basal expression was also evaluated in the K562, Lucena and FEPS (also MDR) cell lines. The transcription factors gene expression was similar in MDR cell lines. The expression of Alox-5 was higher in the non-MDR cell line, while FEPS had the lowest expression of this gene. The opposite pattern was observed for Mdr-1 gene expression. These results suggest that the Alox-5 gene might play a role in the differentiation of these cell lines. PMID- 26852003 TI - The influence of disease and comorbidity risk assessments on the survival of MDS and oligoblastic AML patients treated with 5-azacitidine: A retrospective analysis in ten centers of the "Rete Ematologica Lombarda". AB - 5-Azacytidine is an effective therapy in high risk MDS and oligoblastic AML. This "real life" analysis was made on 185 patients treated with 5-azacytidine in 10 centers afferent to REL ("Rete Ematologica Lombarda"), a network in Lombardia region. The aim was to assess the influence of disease and comorbidity risk assessments on the survival. The results confirm the utility of 5-azacitidine in prolonging OS regardless of advanced age and the presence of comorbidities. They also encourage an early treatment since patients with IPSS-R High risk MDS have better outcome with respect to Very High risk ones. According to the IPSS cytogenetic risk, there was no difference in the outcome between Intermediate and High risk patients. Nevertheless, a poorer cytogenetic risk, according to the IPSS-R cytogenetic stratification, negatively influenced the outcome. PMID- 26852004 TI - The natural history and outcomes for thoracic and abdominal penetrating aortic ulcers. AB - OBJECTIVE: The objective of this report was to define the natural history of penetrating aortic ulcers (PAUs) in the descending thoracic and abdominal aorta. METHODS: Data from consecutive patients with PAU from January 1, 1998 to December 31, 2012 were retrospectively reviewed. Computed tomography (CT) scans were analyzed for anatomic changes. End points analyzed were changes in size, development of symptoms or signs of rupture, morbidity, and mortality. RESULTS: Ninety-three patients were identified; 57 were followed up with two or more CT studies 3 months apart (group 1), and 20 had immediate repair (group 2). Sixteen had one CT scan and no intervention or follow-up and were excluded from analysis. In group 1, mean age was 75 years (29 men, 28 women), with 28 descending thoracic aorta and 29 abdominal aorta PAUs. Fifty patients were asymptomatic, whereas five had pain and two had emboli. Mean follow-up was 38 months (range, 3-108 months). Ulcer growth rate was as follows: length, 2.0 mm/y; depth, 1.2 mm/y; and aortic diameter, 2.2 mm/y. Thirteen (23%) went on to repair at a mean of 37 months after diagnosis because of size (54%; 7/13), rapid growth (31%; 4/13), and high-risk morphology (15%; 2/13). During surveillance, 11 patients died, 10 of unrelated causes, and 1 of rupture after refusing repair. All repairs in group 1 were endovascular. The 30-day surgical mortality was 0%. One patient had an access site complication requiring bypass after descending thoracic aorta PAU repair. At a mean follow-up of 32 months, all ulcers were excluded on CT; one (8%) had a type II endoleak. Group 2 included 13 men and seven women with a mean age of 70 years, with 12 descending thoracic and eight abdominal aorta PAUs. Repair indications were rupture (n = 3), symptoms (n = 10), or size (n = 7) and included one open and 19 endovascular repairs with 0% 30-day mortality. Major complications (3/20; 15%) included myocardial infarction, access site disruption, and hematoma; four of 20 patients had type II endoleaks. CONCLUSIONS: PAU growth rate and risk of rupture are low. Endovascular repair of symptomatic, ruptured, and large PAUs is safe and effective with excellent long-term results. For asymptomatic PAUs, serial CT surveillance is associated with a low rate of rupture or complications. PMID- 26852005 TI - Novel N-acyl-carbazole derivatives as 5-HT7R antagonists. AB - To discover a novel 5-HT7R antagonist for treatment of depression, we designed N acyl-carbazole derivatives which were synthesized and biologically evaluated against 5-HT7R. Among total 30 compounds synthesized, four compounds 27-30 showed good binding affinities with Ki values of <100 nM. The compound 28, 1-(9H carbazol-9-yl)-6-(4-(2-methoxyphenyl)piperazin-1-yl)hexan-1-one, showed good selectivity over other serotonin receptor subtypes and turned out to be a novel selective 5-HT7R antagonist following functional assays. The compound 28 showed moderate activity on hERG channel and good stability in microsomal stability test. The compound 28 exhibited a good pharmacokinetic profile with 67.8% oral bioavailability and good penetration to the brain. The compound 28 was also tested in in vivo depression animal model and showed antidepressant effect in the forced swimming test. Therefore, the selective 5-HT7R antagonist 28 can be considered as a good lead for discovery of novel 5-HT7R antagonists as antidepressants. PMID- 26852006 TI - Air pollution, health and social deprivation: A fine-scale risk assessment. AB - Risk assessment studies often ignore within-city variations of air pollutants. Our objective was to quantify the risk associated with fine particulate matter (PM2.5) exposure in 2 urban areas using fine-scale air pollution modeling and to characterize how this risk varied according to social deprivation. In Grenoble and Lyon areas (0.4 and 1.2 million inhabitants, respectively) in 2012, PM2.5 exposure was estimated on a 10*10m grid by coupling a dispersion model to population density. Outcomes were mortality, lung cancer and term low birth weight incidences. Cases attributable to air pollution were estimated overall and stratifying areas according to the European Deprivation Index (EDI), taking 10ug/m(3) yearly average as reference (counterfactual) level. Estimations were repeated assuming spatial homogeneity of air pollutants within urban area. Median PM2.5 levels were 18.1 and 19.6MUg/m(3) in Grenoble and Lyon urban areas, respectively, corresponding to 114 (5.1% of total, 95% confidence interval, CI, 3.2-7.0%) and 491 non-accidental deaths (6.0% of total, 95% CI 3.7-8.3%) attributable to long-term exposure to PM2.5, respectively. Attributable term low birth weight cases represented 23.6% of total cases (9.0-37.1%) in Grenoble and 27.6% of cases (10.7-42.6%) in Lyon. In Grenoble, 6.8% of incident lung cancer cases were attributable to air pollution (95% CI 3.1-10.1%). Risk was lower by 8 to 20% when estimating exposure through background stations. Risk was highest in neighborhoods with intermediate to higher social deprivation. Risk assessment studies relying on background stations to estimate air pollution levels may underestimate the attributable risk. PMID- 26852008 TI - Intelligence, democracy, and international environmental commitment. AB - This paper investigates the determinants of nations' commitment to environmental protection at the international level by focusing on the role of national intelligence and the level of democracy. The national intelligence is measured by nation's IQ scores. The findings based on a sample of 152 nations provide strong evidence that intelligence has statistically significant impact on ratification of international environmental agreements, and the countries with IQ 10-points above global average are 23% more likely to sign multilateral environmental agreements than others. The findings also demonstrate that it is the combination of high-level of intelligence of nations and democracy, that likely result in international environmental commitments. PMID- 26852007 TI - Exposure to organophosphorus and organochlorine pesticides, perfluoroalkyl substances, and polychlorinated biphenyls in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: The MIREC Study. AB - BACKGROUND: Studies report increases in rates of gestational diabetes mellitus (GDM) over recent decades. Environmental chemicals may increase the risk of diabetes through impacts on glucose metabolism, mitochondrial dysfunction, and endocrine-disrupting mechanisms including effects on pancreatic beta-cell function and adiponectin release. OBJECTIVES: To determine the associations between pesticides, perfluoroalkyl substances (PFASs) and polychlorinated biphenyls (PCBs) measured in early pregnancy and impaired glucose tolerance (IGT) and GDM in a Canadian birth cohort. METHODS: Women enrolled in the Maternal Infant Research on Environmental Chemicals (MIREC) Study were included if they had a singleton delivery and did not have pre-existing diabetes. Exposure variables included three organophosphorus (OP) pesticide metabolites detected in first-trimester urine samples, as well as three organochlorine (OC) pesticides, three PFASs, and four PCBs in first-trimester blood samples. Gestational IGT and GDM were assessed by chart review in accordance with published guidelines. Adjusted logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) for the association between quartiles of environmental chemicals and both gestational IGT and GDM. RESULTS: Of the 2001 women recruited into the MIREC cohort, 1274 met the inclusion criteria and had outcome and biomonitoring data available. Significantly lower odds of GDM were observed in the third and fourth quartiles of dimethylphosphate (DMP) and in the fourth quartile of dimethylthiophosphate (DMTP) in adjusted analyses (DMP Q3: OR=0.2, 95% CI=0.1-0.7; DMP Q4: OR=0.3, 95% CI=0.1-0.8; DMTP: OR=0.3, 95% CI=0.1 0.9). Significantly elevated odds of gestational IGT was observed in the second quartile of perfluorohexane sulfonate (PFHxS) (OR=3.5, 95% CI=1.4-8.9). No evidence of associations with GDM or IGT during pregnancy was observed for PCBs or OC pesticides. CONCLUSIONS: We did not find consistent evidence for any positive associations between the chemicals we examined and GDM or IGT during pregnancy. We observed statistical evidence of inverse relationships between urine concentrations of DMP and DMTP with GDM. We cannot rule out the influence of residual confounding due to unmeasured protective factors, such as nutritional benefits from fruit and vegetable consumption, also associated with pesticide exposure, on the observed inverse associations between maternal OP pesticide metabolites and GDM. These findings require further investigation. PMID- 26852009 TI - Morphological alterations in salivary glands of Rhipicephalus sanguineus ticks (Acari: Ixodidae) exposed to neem seed oil with known azadirachtin concentration. AB - Neem (Azadirachta indica) has attracted the attention of researchers worldwide due to its repellent properties and recognized effects on the morphology and physiology of arthropods, including ticks. Therefore, this study aimed to demonstrate the effects of neem seed oil enriched with azadirachtin on salivary glands of Rhipicephalus sanguineus ticks, targets of great veterinary interest because of their ability to transmit pathogens to dogs. For this, R. sanguineus semi-engorged females were subjected to treatment with neem seed oil, with known azadirachtin concentrations (200, 400 and 600ppm). After dissection, salivary glands were collected and evaluated through morphological techniques in light microscopy, confocal scanning laser microscopy and transmission electron microscopy, so that the possible relation between neem action and further impairment in these ectoparasites feed performance could be established. Neem oil demonstrated a clear dose-dependent effect in the analyzed samples. The agranular (type I) and granular acini (types II and III) showed, particularly in individuals treated with the highest concentrations of the product, cells with irregular shape, intense cytoplasmic disorganization and vacuolation, dilation of rough endoplasmic reticulum lumen, besides alterations in mitochondrial intermembrane space. These morphological damages may indicate modifications in salivary glands physiology, demonstrating the harmful effects of compounds present in neem oil on ticks. These results reinforce the potential of neem as an alternative method for controlling R. sanguineus ticks, instead of synthetic acaricides. PMID- 26852010 TI - Methotrexate in psoriasis under real-world conditions: long-term efficacy and tolerability. PMID- 26852011 TI - Women leaders in hematology: Inspirations & insights. PMID- 26852012 TI - Perception of pain during electromyography in children: A prospective study. AB - INTRODUCTION: Electrodiagnostic examination is perceived as a painful examination. An accurate assessment of its discomfort would be valuable to children, their parents, and clinicians. METHODS: We performed a prospective study of pediatric patients seen over 3 months at 1 center. Pain was scored for both nerve conduction studies and needle electromyography (EMG) on validated scales, depending on the child's age and in comparison with venipuncture. RESULTS: In 100 cases the pain recorded fell within the moderate range on the scoring systems used. Sixty-six percent of patients described the pain to be equivalent or less than that with venipuncture. EMG of > 1 muscle or a proximal muscle produced more pain in patients <4 years of age. CONCLUSIONS: When discussing the test with patients, the physician should reassure the patient and parents regarding the degree of pain that may be encountered, which is not materially different from venipuncture. Muscle Nerve 54: 422-426, 2016. PMID- 26852013 TI - Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High-Fat Diet-Induced Obese Mice. AB - Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT/enhancer-binding protein alpha (C/EBPalpha) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARgamma, C/EBPalpha, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26852014 TI - Exosomes secreted by human urine-derived stem cells could prevent kidney complications from type I diabetes in rats. AB - BACKGROUND: Diabetic nephropathy is one of the most serious complications in patients with diabetes. At present, there are no satisfactory treatments available for diabetic nephropathy. Stem cells are currently the main candidates for the development of new treatments for diabetic nephropathy, as they may exert their therapeutic effects mainly through paracrine mechanisms. Exosomes derived from stem cells have been reported to play an important role in kidney injury. In this article, we try to investigate whether exosomes retrieved from urine stem cells could itself prevent diabetic nephropathy at an early stage in vivo and in vitro. METHODS: Exosomes from conditioned medium of urine-derived stem cells (USCs-Exo) were isolated using ultrafiltration-combined purification methods. USCs-Exo were then verified by morphology, size, and specific biomarkers using transmission electron microscopy, tunable resistive pulse sensing analysis, and western blotting. After establishment of the streptozotocin-induced Sprague Dawley rat model, the effects of USCs-Exo on kidney injury and angiogenesis were observed via weekly tail intravenous injection of USCs-Exo or control until 12 weeks. In vitro, podocytes cultured in high-glucose medium were treated with USCs Exo to test the protective effect of USCs-Exo on podocytic apoptosis. Meanwhile, the potential factors in promoting vascular regeneration in USCs-Exo and urine derived stem cell conditioned medium were investigated by enzyme-linked immunosorbent assay. RESULTS: Urine-derived stem cells were cultured and were verified by positive markers for CD29, CD73, CD90 and CD44 antigens, and negative markers for CD34, CD45 and HLA-DR. USCs-Exo were approximately 50-100 nm spherical vesicles, and the specific markers included CD9, CD63 and CD81. Intravenous injections of USCs-Exo could potentially reduce the urine volume and urinary microalbumin excretion, prevent podocyte and tubular epithelial cell apoptosis, suppress the caspase-3 overexpression and increase glomerular endothelial cell proliferation in diabetic rats. In addition, USCs-Exo could reduce podocytic apoptosis induced by high glucose in vitro. USCs-Exo contained the potential factors, including growth factor, transforming growth factor-beta1, angiogenin and bone morphogenetic protein-7, which may be related with vascular regeneration and cell survival. CONCLUSION: USCs-Exo may have the potential to prevent kidney injury from diabetes by inhibiting podocyte apoptosis and promoting vascular regeneration and cell survival. PMID- 26852015 TI - Novel germline mutations and unclassified variants of BRCA1 and BRCA2 genes in Chinese women with familial breast/ovarian cancer. AB - BACKGROUND: Germline mutations in the BRCA1 and BRCA2 genes greatly increase a woman's risk of developing breast and/or ovarian cancer. The prevalence and distribution of such mutations differ across races/ethnicities. Several studies have investigated Chinese women with high-risk breast cancer, but the full spectrum of the mutations in these two genes remains unclear. METHODS: In this study, 133 unrelated Chinese women with familial breast/ovarian cancer living in Zhejiang, eastern China, were enrolled between the years 2008 and 2014. The complete coding regions and exon-intron boundaries of BRCA1 and BRCA2 were screened by PCR-sequencing assay. Haplotype analysis was performed to confirm BRCA1 and BRCA2 founder mutations. In silico predictions were performed to identify the non-synonymous amino acid changes that were likely to disrupt the functions of BRCA1 and BRCA2. RESULTS: A total of 23 deleterious mutations were detected in the two genes in 31 familial breast/ovarian cancer patients with a total mutation frequency of 23.3% (31/133). The highest frequency of 50.0% (8/16) was found in breast cancer patients with a history of ovarian cancer. The frequencies of BRCA1 and BRCA2 mutations were 13.5 % (18/133) and 9.8% (13/133), respectively. We identified five novel deleterious mutations (c.3295delC, c.3780_3781delAG, c.4063_4066delAATC, c.5161 > T and c.5173insA) in BRCA1 and seven (c.1-40delGA, c.4487delC, c.469_473delAAGTC, c.5495delC, c.6141T > A, c.6359C > G and c.7588C > T) in BRCA2, which accounted for 52.2% (12/23) of the total mutations. Six recurrent mutations were found, including four (c.3780_3781delAG, c.5154G > A, c.5468-1del8 and c.5470_5477del8) in BRCA1 and two (c.3109C > T and c.5682C > G) in BRCA2. Two recurrent BRCA1 mutations (c.5154G > A and c.5468-1del8) were identified as putative founder mutations. We also found 11 unclassified variants, and nine of these are novel. The possibility was that each of the non-synonymous amino acid changes would disrupt the function of BRCA1 and BRCA2 varied according to the different algorithms used. CONCLUSIONS: BRCA1 and BRCA2 mutations accounted for a considerable proportion of hereditary breast/ovarian cancer patients from eastern China and the spectrum of the mutations of these two genes exhibited some unique features. The two BRCA1 putative founder mutations may provide a cost-effective option to screen Chinese population, while founder effects of the two mutations should be investigated in a lager sample size of patients. PMID- 26852016 TI - A qualitative study of hospital pharmacists and antibiotic governance: negotiating interprofessional responsibilities, expertise and resource constraints. AB - BACKGROUND: Antibiotic treatment options for common infections are diminishing due to the proliferation of antimicrobial resistance (AMR). The impact of Antimicrobial Stewardship (AMS) programs seeking to preserve viable antibiotic drugs by governing their use in hospitals has hitherto been limited. Pharmacists have been delegated a critical role in antibiotic governance in AMS teams within hospitals but the experience of pharmacists in influencing antibiotic use has received limited attention. In this study we explore the experiences of pharmacists in antibiotic decision-making in two Australian hospitals. METHODS: We conducted 19 semi-structured interviews to explore hospital-based pharmacists' perceptions and experiences of antibiotic use and governance. The analysis was conducted with NVivo10 software, utilising the framework approach. RESULTS: Three major themes emerged in the pharmacist interviews including (1) the responsibilities of pharmacy in optimising antibiotic use and the interprofessional challenges therein; (2) the importance of antibiotic streamlining and the constraints placed on pharmacists in achieving this; and (3) the potential, but often under-utilised expertise, pharmacists bring to antibiotic optimisation. CONCLUSIONS: Pharmacists have a critical role in AMS teams but their capacity to enact change is limited by entrenched interprofessional dynamics. Identifying how hospital pharmacy's antibiotic gatekeeping is embedded in the interprofessional nature of clinical decision making and limited by organisational environment has important implications for the implementation of hospital policies seeking to streamline antibiotic use. Resource constraints (i.e. time limitation and task prioritisation) in particular limit the capacity of pharmacists to overcome the interprofessional barriers through development of stronger collaborative relationships. The results of this study suggest that to enact change in antibiotic use in hospitals, pharmacists must be supported in their negotiations with doctors, have increased presence on hospital wards, and must be given opportunities to pass on specialist knowledge within multidisciplinary clinical teams. PMID- 26852017 TI - Gene set analysis using sufficient dimension reduction. AB - BACKGROUND: Gene set analysis (GSA) aims to evaluate the association between the expression of biological pathways, or a priori defined gene sets, and a particular phenotype. Numerous GSA methods have been proposed to assess the enrichment of sets of genes. However, most methods are developed with respect to a specific alternative scenario, such as a differential mean pattern or a differential coexpression. Moreover, a very limited number of methods can handle either binary, categorical, or continuous phenotypes. In this paper, we develop two novel GSA tests, called SDRs, based on the sufficient dimension reduction technique, which aims to capture sufficient information about the relationship between genes and the phenotype. The advantages of our proposed methods are that they allow for categorical and continuous phenotypes, and they are also able to identify a variety of enriched gene sets. RESULTS: Through simulation studies, we compared the type I error and power of SDRs with existing GSA methods for binary, triple, and continuous phenotypes. We found that SDR methods adequately control the type I error rate at the pre-specified nominal level, and they have a satisfactory power to detect gene sets with differential coexpression and to test non-linear associations between gene sets and a continuous phenotype. In addition, the SDR methods were compared with seven widely-used GSA methods using two real microarray datasets for illustration. CONCLUSIONS: We concluded that the SDR methods outperform the others because of their flexibility with regard to handling different kinds of phenotypes and their power to detect a wide range of alternative scenarios. Our real data analysis highlights the differences between GSA methods for detecting enriched gene sets. PMID- 26852018 TI - Large-scale Anopheles arabiensis egg quantification methods for mass-rearing operations. AB - BACKGROUND: The success of the sterile insect technique relies, among other things, on the continuous release of over flooding numbers of sexually competitive sterile males into the target area. To produce sufficiently large quantities of sterile males, rearing protocols need to be optimized including the development and validation of a standardized egg quantification method. METHODS: Batches of 1000 freshly laid eggs collected from standard rearing cages were counted, gently dried under laboratory conditions (27 +/- 1 degrees C, 75 +/- 5 % RH) and combined so that 1000-8000 eggs were weighed, to calculate the correlation between weight and number. The actual counted egg number and the egg number estimated by weighing were further compared for samples of 1000, 3000 and 4000 eggs collected from both standard and mass-rearing cages. The effect of drying, brushing and weighing on egg hatch rate was evaluated in three samples each of 1000 fresh and 1000 dried eggs, and in batches of 1000, 3000 and 4000 dried eggs. Pupal production and adult life history traits were assessed for dried eggs hatched and reared in mass-rearing trays. Expected egg numbers and actual observed mean egg numbers were compared after gentle drying, and after applying a rapid drying method exposure to wind speed of 1.8 m/s for 30 min. RESULTS: A significant positive relationship between the number of dried eggs and egg weight was observed and the equation 'Weight (mg) = (0.00399 * Number of counted eggs) + 0.536 was derived. The actual counted mean egg number and the egg number estimated by weighing were similar for samples from small rearing cages but significantly lower for samples of 3000 and 4000 egg samples collected from mass-rearing cages. No negative effect of the drying, brushing and weighing process on egg hatch rate was observed. No significant difference was observed in any life history trait between adults reared from dried or from fresh eggs up to twenty-one days post emergence. The mean number of eggs counted from a given replicate's weight was significantly higher for egg batches fast dried with a suction device compared to those dried with a gentle drying method (fast: 1075 +/ 9, gentle: 1024 +/- 7). CONCLUSION: An equation has been derived to allow accurate quantification of dried Anopheles arabiensis eggs based on weight, enabling more accurate quantification of eggs for consistent larval rearing density to be achieved. Eggs can be dried for weighing in a manner which does not impair the quality of resulting adults. PMID- 26852019 TI - Prevalence of hemorrhagic fever with renal syndrome in Yiyuan County, China, 2005 2014. AB - BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) is highly endemic in mainland China, where human cases account for 90 % of the total global cases. Yiyuan County is one of the most serious affected areas in China. Therefore, there is an urgent need for monitoring and predicting HFRS incidence in Yiyuan to make the control of HFRS more effective. METHODS: The study was based on the reported cases of HFRS from the National Notifiable Disease Surveillance System. The demographic and spatial distributions of HFRS in Yiyuan were established. Then we fit autoregressive integrated moving average (ARIMA) models and predict the HFRS epidemic trend. RESULTS: There were 362 cases reported in Yiyuan during the 10-year study period. The human infections in the fall and winter reflected a seasonal characteristic pattern of Hantaan virus (HTNV) transmission. The best model was ARIMA (2, 1, 1) * (0, 1, 1)12 (AIC value 516.86) with a high validity. CONCLUSION: The ARIMA model fits the fluctuations in HFRS frequency and it can be used for future forecasting when applied to HFRS prevention and control. PMID- 26852020 TI - Biomechanical simulation of thorax deformation using finite element approach. AB - BACKGROUND: The biomechanical simulation of the human respiratory system is expected to be a useful tool for the diagnosis and treatment of respiratory diseases. Because the deformation of the thorax significantly influences airflow in the lungs, we focused on simulating the thorax deformation by introducing contraction of the intercostal muscles and diaphragm, which are the main muscles responsible for the thorax deformation during breathing. METHODS: We constructed a finite element model of the thorax, including the rib cage, intercostal muscles, and diaphragm. To reproduce the muscle contractions, we introduced the Hill-type transversely isotropic hyperelastic continuum skeletal muscle model, which allows the intercostal muscles and diaphragm to contract along the direction of the fibres with clinically measurable muscle activation and active force-length relationship. The anatomical fibre orientations of the intercostal muscles and diaphragm were introduced. RESULTS: Thorax deformation consists of movements of the ribs and diaphragm. By activating muscles, we were able to reproduce the pump-handle and bucket-handle motions for the ribs and the clinically observed motion for the diaphragm. In order to confirm the effectiveness of this approach, we simulated the thorax deformation during normal quiet breathing and compared the results with four-dimensional computed tomography (4D-CT) images for verification. CONCLUSIONS: Thorax deformation can be simulated by modelling the respiratory muscles according to continuum mechanics and by introducing muscle contractions. The reproduction of representative motions of the ribs and diaphragm and the comparison of the thorax deformations during normal quiet breathing with 4D-CT images demonstrated the effectiveness of the proposed approach. This work may provide a platform for establishing a computational mechanics model of the human respiratory system. PMID- 26852021 TI - A framework for analyzing the robustness of movement models to variable step discretization. AB - When sampling animal movement paths, the frequency at which location measurements are attempted is a critical feature for data analysis. Important quantities derived from raw data, e.g. travel distance or sinuosity, can differ largely based on the temporal resolution of the data. Likewise, when movement models are fitted to data, parameter estimates have been demonstrated to vary with sampling rate. Thus, biological statements derived from such analyses can only be made with respect to the resolution of the underlying data, limiting extrapolation of results and comparison between studies. To address this problem, we investigate whether there are models that are robust against changes in temporal resolution. First, we propose a mathematically rigorous framework, in which we formally define robustness as a model property. We then use the framework for a thorough assessment of a range of basic random walk models, in which we also show how robustness relates to other probabilistic concepts. While we found robustness to be a strong condition met by few models only, we suggest a new method to extend models so as to make them robust. Our framework provides a new systematic, mathematically founded approach to the question if, and how, sampling rate of movement paths affects statistical inference. PMID- 26852022 TI - Combinatorial synthesis of deuterium-enriched (S)-oxybutynin. AB - The concept of deuterium enrichment has gained more attention due to its advantages in the studies of clinical pharmacokinetics and metabolic profiles. In addition, it is cost and time efficient to develop deuterium-enriched drugs. Herein we built a combinatorial library of deuterated (S)-oxybutynins which all 8 D-compounds were characterized by MS, [Formula: see text] NMR and [Formula: see text]C NMR. PMID- 26852025 TI - Semi-Rational Design of Geobacillus stearothermophilus L-Lactate Dehydrogenase to Access Various Chiral alpha-Hydroxy Acids. AB - Chiral alpha-hydroxy acids (AHAs) are rapidly becoming important synthetic building blocks, in particular for the production of pharmaceuticals and other fine chemicals. Chiral compounds of a variety of functionalities are now often derived using enzymes, and L-lactate dehydrogenase from the thermophilic organism Geobacillus stearothermophilus (bsLDH) has the potential to be employed for the industrial synthesis of chiral alpha-hydroxy acids. Despite the thorough characterization of this enzyme, generation of variants with high activity on non natural substrates has remained difficult and therefore limits the use of bsLDH in industry. Here, we present the engineering of bsLDH using semi-rational design as a method of focusing screening in a small and smart library for novel biocatalysts. In this study, six mutant libraries were designed in an effort to expand the substrate range of bsLDH. The eight variants identified as having enhanced activity toward the selected alpha-keto acids belonged to the same library, which targeted two positions simultaneously. These new variants now may be useful biocatalysts for chiral synthesis of alpha-hydroxy acids. PMID- 26852023 TI - Genetics of structural connectivity and information processing in the brain. AB - Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 * 10-08). Suggestive associations (Meta P value <1 * 10-06) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 * 10-08). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 * 10-07). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 * 10-08), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 * 10-07) and the multimodal analysis (Fisher P value = 1 * 10-07). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain. PMID- 26852026 TI - Single-Step Purification and Characterization of A Recombinant Serine Proteinase Inhibitor from Transgenic Plants. AB - Expression of recombinant therapeutic proteins in transgenic plants has a tremendous impact on safe and economical production of biomolecules for biopharmaceutical industry. The major limitation in their production is downstream processing of recombinant protein to obtain higher yield and purity of the final product. In this study, a simple and rapid process has been developed for purification of therapeutic recombinant alpha1-proteinase inhibitor (ralpha1 PI) from transgenic tomato plants, which is an abundant serine protease inhibitor in human serum and chiefly inhibits the activity of neutrophil elastase in lungs. We have expressed ralpha1-PI with modified synthetic gene in transgenic tomato plants at a very high level (?3.2 % of total soluble protein). The heterologous protein was extracted with (NH4)2SO4 precipitation, followed by chromatographic separation on different matrices. However, only immunoaffinity chromatography resulted into homogenous preparation of ralpha1-PI with 54 % recovery. The plant purified ralpha1-PI showed molecular mass and structural conformation comparable to native serum alpha1-PI, as shown by mass spectrometry and optical spectroscopy. The results of elastase inhibition assay revealed biological activity of the purified ralpha1-PI protein. This work demonstrates a simple and efficient one-step purification of ralpha1-PI from transgenic plants, which is an essential prerequisite for further therapeutic development. PMID- 26852024 TI - Upper cervical and upper thoracic manipulation versus mobilization and exercise in patients with cervicogenic headache: a multi-center randomized clinical trial. AB - BACKGROUND: Although commonly utilized interventions, no studies have directly compared the effectiveness of cervical and thoracic manipulation to mobilization and exercise in individuals with cervicogenic headache (CH). The purpose of this study was to compare the effects of manipulation to mobilization and exercise in individuals with CH. METHODS: One hundred and ten participants (n = 110) with CH were randomized to receive both cervical and thoracic manipulation (n = 58) or mobilization and exercise (n = 52). The primary outcome was headache intensity as measured by the Numeric Pain Rating Scale (NPRS). Secondary outcomes included headache frequency, headache duration, disability as measured by the Neck Disability Index (NDI), medication intake, and the Global Rating of Change (GRC). The treatment period was 4 weeks with follow-up assessment at 1 week, 4 weeks, and 3 months after initial treatment session. The primary aim was examined with a 2-way mixed-model analysis of variance (ANOVA), with treatment group (manipulation versus mobilization and exercise) as the between subjects variable and time (baseline, 1 week, 4 weeks and 3 months) as the within subjects variable. RESULTS: The 2X4 ANOVA demonstrated that individuals with CH who received both cervical and thoracic manipulation experienced significantly greater reductions in headache intensity (p < 0.001) and disability (p < 0.001) than those who received mobilization and exercise at a 3-month follow-up. Individuals in the upper cervical and upper thoracic manipulation group also experienced less frequent headaches and shorter duration of headaches at each follow-up period (p < 0.001 for all). Additionally, patient perceived improvement was significantly greater at 1 and 4-week follow-up periods in favor of the manipulation group (p < 0.001). CONCLUSIONS: Six to eight sessions of upper cervical and upper thoracic manipulation were shown to be more effective than mobilization and exercise in patients with CH, and the effects were maintained at 3 months. TRIAL REGISTRATION: NCT01580280 April 16, 2012. PMID- 26852027 TI - The Proteolytic Activity of Philibertia gilliesii Latex. Purification of Philibertain g II. AB - The latex from the patagonic plant Philibertia gilliesii Hook. et Arn. (Apocynaceae) is a milky-white suspension containing a proteolytic system constituted by several cysteine endopeptidases. A proteolytic preparation (philibertain g) from the latex of P. gilliesii fruits was obtained and characterized to evaluate its potential use in bioprocesses. Philibertain g contained 1.2 g/L protein and a specific (caseinolytic) activity of 7.0 Ucas/mg protein. It reached 80 % of its maximum caseinolytic activity in the pH 7-10 range, retained 80 % of the original activity after 2 h of incubation at temperatures ranging from 25 to 45 degrees C and could be fully inactivated after 5 min at 75 degrees C. Philibertain g retained 60 % of the initial activity even at 1 M NaCl and was able to hydrolyze proteins from stickwater one, of the main waste effluents generated during fishmeal production. Furthermore, as a contribution to the knowledge of the proteolytic system of P. gilliesii, we are reporting the purification of a new peptidase, named philibertain g II (pI 9.4, molecular mass 23,977 Da, N-terminus LPESVDWREKGVVFPXRNQ) isolated from philibertain g through a purification scheme including acetone fractionation, cation exchange, molecular exclusion chromatography, and ultrafiltration. PMID- 26852028 TI - Comment on Vergeldt et al.: Risk factors for pelvic organ prolapse and its recurrence: a systematic review. PMID- 26852029 TI - Response to the letter to the editor by Shek et al. on Vergeldt et al: Risk factors for pelvic organ prolapse and its recurrence: a systematic review. PMID- 26852030 TI - Towards an optimal paradigm for intraoperative auditory nerve monitoring with auditory steady state responses. AB - Auditory steady state responses (ASSR) may offer an alternative to brainstem auditory evoked potentials for monitoring of the auditory nerve during surgical procedures. In the current study, we evaluated the influence of noise on ASSR characteristics in total intravenous anesthesia (TIVA). Simulated ASSR in real noise recorded during surgery under TIVA were constructed with known parameters. Influence of amplitude, modulation frequency, averaging sweeps and detection threshold on ASSR were evaluated. High amplitude, more sweeps and a liberal threshold facilitated detection. High amplitude ASSR (80 nV) were detected in up to 45 % with 16 s of data, in 80-90 % with 112 s. Near-threshold ASSR were detected in 0.8-25 %. False positives ranged between 0.3 and 10.3 %. Number of sweeps did not influence false positives. Amplitude errors varied between -61 and +39 % and improved with more averages but not with different thresholds. Modulation rate demonstrated the strongest influence on all parameters. 110 Hz yielded best, 90 Hz the worst results. Choice of parameters strongly influences detection and characteristics of ASSR. Optimal parameters enabled detection after 16 s in 45 %. Due to specific noise characteristics, modulation has a critical impact, which is currently not sufficiently recognized in ASSR studies. PMID- 26852032 TI - HIV and STI Testing and Related Factors Among Men Who Have Sex with Men in Estonia. AB - HIV and sexually transmitted infections (STI) testing rates among men who have sex with men (MSM) in Estonia are low. We collected data from 265 MSM in a national, online survey. Lifetime HIV testing was related to risky sexual behaviors and contacts with health care services, while lifetime STI testing was related only to contacts with health care services. In addition, some personal values were significant predictors of testing. For example, high achievement (personal success through demonstrating competence according to social standards) had a negative impact on lifetime HIV testing, and high interpersonal conformity (avoiding upsetting others) had a negative impact on lifetime STI testing. The results demonstrate the need to develop gay-friendly health services and to recognize the role of personal values and individual differences in values when designing attractive interventions to increase HIV/STI testing rates among MSM. PMID- 26852033 TI - Intracranial multifocal plasma cell granuloma: a case with multiple operations without recurrence of surgically removed lesions. PMID- 26852031 TI - Coronaviruses and the human airway: a universal system for virus-host interaction studies. AB - Human coronaviruses (HCoVs) are large RNA viruses that infect the human respiratory tract. The emergence of both Severe Acute Respiratory Syndrome and Middle East Respiratory syndrome CoVs as well as the yearly circulation of four common CoVs highlights the importance of elucidating the different mechanisms employed by these viruses to evade the host immune response, determine their tropism and identify antiviral compounds. Various animal models have been established to investigate HCoV infection, including mice and non-human primates. To establish a link between the research conducted in animal models and humans, an organotypic human airway culture system, that recapitulates the human airway epithelium, has been developed. Currently, different cell culture systems are available to recapitulate the human airways, including the Air-Liquid Interface (ALI) human airway epithelium (HAE) model. Tracheobronchial HAE cultures recapitulate the primary entry point of human respiratory viruses while the alveolar model allows for elucidation of mechanisms involved in viral infection and pathogenesis in the alveoli. These organotypic human airway cultures represent a universal platform to study respiratory virus-host interaction by offering more detailed insights compared to cell lines. Additionally, the epidemic potential of this virus family highlights the need for both vaccines and antivirals. No commercial vaccine is available but various effective antivirals have been identified, some with potential for human treatment. These morphological airway cultures are also well suited for the identification of antivirals, evaluation of compound toxicity and viral inhibition. PMID- 26852034 TI - Stereotactic biopsy approach to the upper clivus through the middle fossa floor that avoids pneumatised cavities and the intradural compartment. AB - BACKGROUND: Biopsies of clival lesions are usually performed, under general anaesthesia, through an anterior endoscopic approach or, alternatively, through a trans-nasal or trans-oral stereotactic approach. METHODS: A 57-year-old man with a symptomatic osteolytical lesion of the clivus, who refused general anaesthesia, underwent a sterotactically guided biopsy of the lesion by an antero-lateral approach through the temporal and sphenoid bones. RESULTS: Biopsy was successfully performed and the resulting diagnosis was myeloma. The patient was comfortable during and after surgery and there were no complications. CONCLUSIONS: The present stereotactic antero-lateral approach to the biopsy of the upper clivus can be considered an useful adjunct to the current trans-oral and transnasal approaches that often require general anaesthesia. PMID- 26852035 TI - Stress during neurosurgery: no need to worry? PMID- 26852036 TI - Selective amygdalohippocampectomy via trans-superior temporal gyrus keyhole approach. AB - BACKGROUND: Hippocampal sclerosis is the most common cause of drug-resistant epilepsy amenable for surgical treatment and seizure control. The rationale of the selective amygdalohippocampectomy is to spare cerebral tissue not included in the seizure generator. METHOD: Describe the selective amygdalohippocampectomy through the trans-superior temporal gyrus keyhole approach. CONCLUSION: Selective amygdalohippocampectomy for temporal lobe epilepsy is performed when the data (semiology, neuroimaging, electroencephalography) point to the mesial temporal structures. The trans-superior temporal gyrus keyhole approach is a minimally invasive and safe technique that allows disconnection of the temporal stem and resection of temporomesial structures. PMID- 26852037 TI - Enzymatic synthesis of lactosylated and sialylated derivatives of epothilone A. AB - Epothilone A is a derivative of 16-membered polyketide natural product, which has comparable chemotherapeutic effect like taxol. Introduction of sialic acids to these chemotherapeutic agents could generate interesting therapeutic glycoconjugates with significant effects in clinical studies. Since, most of the organisms biosynthesize sialic acids in their cell surface, they are key mediators in cellular events (cell-cell recognition, cell-matrix interactions). Interaction between such therapeutic sugar parts and cellular polysaccharides could generate interesting result in drugs like epothilone A. Based on this hypothesis, epothilone A glucoside (epothilone A 6-O-beta-D-glucoside) was further decorated by conjugating enzymatically galactose followed by sialic acids to generate epothilone A 7-O-beta-D-glucopyranosyl, 4'-O-alpha-D-galactoside i.e., lactosyl epothilone A (lac epoA) and two sialosides of epothilone A namely epothilone A 7-O-beta-D-glucopyranosyl, 4'-O-alpha-D-galactopyranosyl 3"-O-alpha N-acetyl neuraminic acid and epothilone A 7-O-beta-D-glucopyranosyl, 4'-O-alpha-D galactopyranosyl 6"-O-alpha-N-acetylneuraminic acid i.e., 3'sialyllactosyl epothilone A: 3'SL-epoA, and 6'sialyllactosyl epothilone A: 6'SL-epoA, respectively. These synthesized analogs were spectroscopically analyzed and elucidated, and biologically validated using HUVEC and HCT116 cancer cell lines. PMID- 26852038 TI - Marine steroid derived from Acropora formosa enhances mitochondrial-mediated apoptosis in non-small cell lung cancer cells. AB - p53 pathway has been revealed to mediate cellular stress responses and trigger DNA repair, cell cycle arrest, senescence, and apoptosis. We isolated 2 ethoxycarbonyl-2-beta-hydroxy-A-nor-cholest-5-ene-4one (ECHC) from butanol extracts of scleractinian coral Acropora formosa and reported its potential antioxidant and antimicrobial activity as well as less toxicity against zebrafish Danio rerio. In the present study, we intend to explore p53-mediated apoptosis pathway enhanced by ECHC in A549 human non-small cell lung cancer cell lines. This report shows that ECHC increases ROS generation and sensitizes mitochondrial membrane that leads to the release of cytochrome C (Cyto C) into cytosol. Further, ECHC decreases the expression of antiapoptotic genes such as TNF-alpha, IL-8, Bcl2, MMP2, and MMP9 which are actively involved in cancer cell proliferation, invasion, and metastasis etc. It also increases the expression of apoptotic genes Cyto C, Bax, and p21, which are responsible for cell cycle arrest and cell death. The tumor suppressor p53 was also observed to be upregulated during ECHC treatment in untransformed cells and was more likely to result in cell cycle arrest, senescence, and apoptosis. Finally, ECHC also down regulates the expression of caspase-9 and caspase-3 which are the death stage of intrinsic apoptosis. Our findings suggested that ECHC enhances ROS generation and mitochondrial sensitization determines the threshold for irreversible p53 mediated intrinsic apoptosis pathway. PMID- 26852039 TI - CLPTM1L polymorphism as a protective factor for lung cancer: a case-control study in southern Chinese population. AB - Variants of the cleft lip and palate trans-membrane 1 like (CLPTM1L) gene, located on chromosome 5p15.33, were previously determined to influence lung cancer susceptibility. Here, we performed a case-control study to examine the potential association of CLPTM1L single nucleotide polymorphisms (SNPs) with lung cancer in a Chinese Han population. We selected four SNPs in the CLPTM1L gene that were previously reported to be associated with lung cancer. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to estimate the strength of the relationship between each CLPTM1L SNP and lung cancer risk. Allelic model analysis revealed that the minor alleles of all four SNPs were significantly associated with decreased lung cancer risk. Similar significant results were detected using genetic model analysis. In addition, we observed a protective effect of haplotype "TT" in the CLPTM1L gene. Our results verified that certain CLPTM1L polymorphisms are protective factors against lung cancer in a southern Chinese Han population and may be potential diagnostic and molecular markers for lung cancer patients. PMID- 26852041 TI - Variation of mandibular sexual dimorphism across human facial patterns. AB - This study analysed how sex-specific features differed in male and female adult mandibles throughout the spectrum of vertical facial patterns (i.e., meso-, dolicho- and brachyfacial) and sagittal variations (the so-called skeletal Classes I, II and III; normal maxillo-mandibular relationship, maxillary prognathism vs. mandibular retrognathism, and maxillary retrognathism vs. mandibular prognathism, respectively). Specifically, we test the hypothesis that sexual dimorphism in the mandible is independent of such facial vertical and sagittal patterns. A sample of 187 European adults (92 males, 95 females; age range, 20-30 years; mean age 25.6 years, sd=4.2 years) from Granada (southern Spain) were randomly selected and grouped according to the standard cephalometric criteria of the sagittal and vertical patterns. Geometric morphometrics were used to analyse the size (centroid size) and shape (principal components analysis, mean shape comparisons) of the mandible. The patterns of sexual dimorphism were evaluated with a generalised linear model with interaction term. We found that sagittal and vertical facial patterns are associated with different mandibular morphologies (size and shape). Also, sexual dimorphism was present in all comparisons. The hypothesis was rejected only for vertical facial patterns. That is, the nature of sexual dimorphism was similar among the skeletal classes but different (e.g., distribution of dimorphic variables, interaction term) in meso-, dolicho-, and brachyfacial mandibles. In conclusion, sex-specific mandibular traits behave in a different way across vertical facial patterns. These results imply that an assessment of the vertical facial pattern of the individual is required before a sexual diagnosis of the mandible is proposed. PMID- 26852040 TI - A phase 3, multi-center, multinational, randomized, double-blind, placebo controlled study to evaluate the efficacy and safety of levofloxacin inhalation solution (APT-1026) in stable cystic fibrosis patients. AB - RATIONALE: For patients with cystic fibrosis (CF), the use of inhaled antibiotics has become standard of care to suppress chronic Pseudomonas airways infection. There are limited antibiotic options formulated and approved for inhaled use and antibiotic efficacies attenuate over time, making additional inhaled antibiotic classes desirable. APT-1026 (levofloxacin inhalation solution, LIS) is a fluoroquinolone in development for management of chronic P. aeruginosa airways infection in patients with CF. OBJECTIVES: To compare the safety and efficacy of a 28-day course of treatment with LIS 240mg or placebo BID in persons >=12years old with CF and chronic P. aeruginosa infection. METHODS: A multinational, randomized (2:1), double-blinded study of LIS and placebo over 28days in CF patients >=12years with chronic P. aeruginosa infection. Time to exacerbation was the primary endpoint. FEV1 (% predicted) and patient-reported quality of life were among secondary endpoints. MAIN RESULTS: Baseline demographics for 330 subjects (LIS=220) were similar although significantly more patients randomized to LIS had experienced multiple exacerbations in the year prior to study entry. There was no statistically significant difference in protocol-defined pulmonary exacerbations between treatment arms. Relative change in FEV1% predicted from baseline was significantly greater for patients randomized to LIS compared to those randomized to placebo (mean difference 1.31%, p=0.01 [95% CI 0.27, 2.34%]). LIS was well-tolerated, with dysguesia the most frequent adverse event. CONCLUSIONS: LIS did not demonstrate a difference in time to next exacerbation when compared to placebo. Reasons for this result are discussed but may be due to an imbalance in the frequency of prior pulmonary exacerbations between the two groups. An improvement in FEV1 (% predicted) at 28days was observed and LIS was well tolerated. LIS is safe and has a potential role in the management of CF patients with chronic P. aeruginosa. PMID- 26852043 TI - Cancer nanomedicine: challenges and opportunities. PMID- 26852042 TI - Investigation on environmental factors of waste plastics into oil and its emulsion to control the emission in DI diesel engine. AB - Rapid depletion of conventional fossil fuel resources, their rising prices and environmental issues are the major concern of alternative fuels. On the other hand waste plastics cause a very serious environmental dispute because of their disposal problems. Waste plastics are one of the promising factors for fuel production because of their high heat of combustion and their increasing availability in local communities. In this study, waste plastic oil (WPO) is tested in DI diesel engine to evaluate its performance and emission characteristics. Results showed that oxides of nitrogen (NOx) emission get increased with WPO when compared to diesel oil. Further, the three phase (O/W/O) plastic oil emulsion is prepared with an aid of ultrasonicater according to the %v (10, 20 & 30). Results expose that brake thermal efficiency (BTE) is found to be increased. NOx and smoke emissions were reduced up to 247ppm and 41% respectively, when compared to diesel at full load condition with use of 30% emulsified WPO. PMID- 26852044 TI - Five reasons to not prescribe opioids. PMID- 26852046 TI - Challenges of chronic kidney disease prevention. PMID- 26852047 TI - What can we do to help Australians die the way they want to? PMID- 26852048 TI - Threats and abuse: the price public health campaigners pay. PMID- 26852049 TI - The need to upskill rural general practitioners in mental health care. PMID- 26852050 TI - The need to upskill rural general practitioners in mental health care. PMID- 26852051 TI - Summary statement: new guidelines for the management of paracetamol poisoning in Australia and New Zealand. PMID- 26852052 TI - Medicare Local-Local Health Network partnerships in South Australia: lessons for Primary Health Networks. AB - OBJECTIVES: To examine the partnerships in population health planning between Medicare Locals (MLs) and Local Health Networks (LHNs) in South Australia, and the factors that facilitated or constrained collaborations, to offer lessons for LHNs and Primary Health Networks. DESIGN, PARTICIPANTS AND SETTING: We conducted a qualitative study using individual interviews with key informants (executive or program leader staff) from the five South Australian MLs and the five South Australian LHNs. A total of 34 interviews were conducted between March and July 2014. RESULTS: Significant work was undertaken by MLs in the process of population health planning and needs assessment. Participants from both MLs and LHNs described examples of collaborative work, including data sharing and synthesis, program implementation and community consultation. The focus of LHNs on acute and intermediate care, the lack of system-level strategies to support collaboration, and constant policy and structural changes leading to uncertainty in the primary health care landscape were perceived as key barriers to collaboration. CONCLUSIONS: The experience of MLs and their achievements in building relationships and trust with stakeholders in their regions, including LHNs, provide valuable lessons for the new Primary Health Networks in Australia. PMID- 26852053 TI - Suboptimal medication-related quality of care preceding hospitalisation of older patients. AB - OBJECTIVE: To examine the prevalence of suboptimal medication-related processes of care before the hospitalisation of older patients. DESIGN AND SETTING: We conducted a retrospective cohort study using a clinical indicator set related to medication management that has been validated by an expert panel as consisting of suboptimal aspects of medication use that clinicians should be able to foresee and avoid. Australian Government Department of Veterans' Affairs administrative claims data between 1 July 2007 and 30 June 2012 were analysed according to these clinical indicators to assess medication-related processes of care preceding hospitalisation. PARTICIPANTS: Veterans with one or more hospitalisations in Australia for a condition defined by the clinical indicator set. MAIN OUTCOME MEASURE: Prevalence of suboptimal medication-related processes of care before hospitalisation as a proportion of all hospitalisations defined by diagnoses in the clinical indicator set. RESULTS: During the 5-year study period, there were 164,813 hospitalisations with primary diagnoses for conditions included in the clinical indicator set, encompassing 83,430 patients. The overall proportion of hospitalisations that were preceded by suboptimal medication-related processes of care was 25.2% (41,546 hospitalisations); 34.5% of patients (28,807 patients) had at least one hospitalisation and 10.4% (8640 patients) had two or more hospitalisations preceded by suboptimal medication-related processes of care. At least one in 10 hospitalisations for chronic heart failure, ischaemic stroke, asthma, gastrointestinal ulcer or bleeding, fracture, renal failure or nephropathy, hyperglycaemia or hypoglycaemia were preceded by suboptimal medication-related processes of care. CONCLUSIONS: This study highlights conditions for which there are evidence-practice gaps in medication management in the older population. Routine prospective monitoring of these evidence-based, validated, medication-related clinical indicators provides a means for quality improvement in the management of common chronic conditions. PMID- 26852054 TI - Rheumatic heart disease in Indigenous children in northern Australia: differences in prevalence and the challenges of screening. AB - OBJECTIVES: To compare regional differences in the prevalence of rheumatic heart disease (RHD) detected by echocardiographic screening in high-risk Indigenous Australian children, and to describe the logistical and other practical challenges of RHD screening. DESIGN: Cross-sectional screening survey performed between September 2008 and November 2010. SETTING: Thirty-two remote communities in four regions of northern and central Australia. PARTICIPANTS: 3946 Aboriginal or Torres Strait Islander children aged 5-15 years. INTERVENTION: Portable echocardiography was performed by cardiac sonographers. Echocardiograms were recorded and reported offsite by a pool of cardiologists. MAIN OUTCOME MEASURES: RHD was diagnosed according to 2012 World Heart Federation criteria. RESULTS: The prevalence of definite RHD differed between regions, from 4.7/1000 in Far North Queensland to 15.0/1000 in the Top End of the Northern Territory. The prevalence of definite RHD was greater in the Top End than in other regions (odds ratio, 2.3; 95% CI, 1.2-4.6, P = 0.01). Fifty-three per cent of detected cases of definite RHD were new cases; the prevalence of new cases of definite RHD was 4.6/1000 for the entire sample and 7.0/1000 in the Top End. Evaluation of socioeconomic data suggests that the Top End group was the most disadvantaged in our study population. CONCLUSIONS: The prevalence of definite RHD in remote Indigenous Australian children is significant, with a substantial level of undetected disease. Important differences were noted between regions, with the Top End having the highest prevalence of definite RHD, perhaps explained by socioeconomic factors. Regional differences must be considered when evaluating the potential benefit of widespread echocardiographic screening in Australia. PMID- 26852055 TI - Tattoo-associated mycobacterial infections: an emerging public health issue. PMID- 26852056 TI - Photobacterium damselae and Vibrio harveyi hand infection from marine exposure. PMID- 26852057 TI - Steroid-induced cardiomyopathy. PMID- 26852058 TI - Warfarin or excipient allergy: a clinical dilemma resolved. PMID- 26852059 TI - Can a medical researcher have too many publications? PMID- 26852062 TI - Ciclesonide-induced bronchospasm: an important but preventable side effect. PMID- 26852063 TI - You are not Robinson Crusoe. PMID- 26852064 TI - Intramammary metastasis of renal cell carcinoma: A diagnostic trap. PMID- 26852065 TI - [Cerebral venous thrombosis during pregnancy]. PMID- 26852066 TI - Familial dilated cardiomyopathy diagnosis is commonly overlooked at the time of transplant listing. AB - BACKGROUND: The prevalence and clinical characteristics of familial dilated cardiomyopathy (FDCM) among patients with end stage heart failure (ESHF) has yet to be elucidated. We sought to determine the prevalence of FDCM in ESHF in the United Network for Organ Sharing (UNOS) registry and compare this with center specific data from a large tertiary teaching hospital. Patients with a banked UNOS diagnosis of dilated cardiomyopathy (DCM) whose care originated at our center then underwent detailed pedigree analysis in order to determine the true prevalence of FDCM. METHODS AND RESULTS: A total of 16,091 patients with DCM from all centers were identified in the UNOS registry of whom 492 carried the diagnosis of FDCM (3.1%). Patients with the diagnosis of FDCM tended to be younger (42 versus 49 years old in idiopathic dilated cardiomyopathy (IDCM), p=0.001), were less likely to have diabetes (7.8% versus 16.5% in IDCM, p<0.0001), had slightly lower creatinine (1.2 versus 1.4 in IDCM, p=0.0001) and were more likely to have a panel reactive antibody level >= 20% (62.1% versus 44.7% in IDCM, p<0.0001). Consecutive living adult patients with ESHF were identified from the UNOS registry that had been treated at the Yale Center for Advanced Heart Failure (YCAHF). After excluding all diagnoses that did not include any form of non-ischemic DCM, 73 patients met the inclusion criteria. Center-specific UNOS data showed pre-pedigree analysis diagnosis of FDCM in 4.12% of patients (3 out of 73), consistent with that found in the UNOS database for all centers. However, after detailed family history and pedigree analysis, 19 (26%) of 73 patients were found to have FDCM, while the remaining 54 were found to have IDCM. Echocardiographic findings including mitral regurgitation, mitral valve annulus and left ventricular end diastolic dimension were not significantly different between groups when adjusting for multiple testing. CONCLUSIONS: The diagnosis of FDCM was missed in the majority of patients with end stage heart failure enrolled in the UNOS database, as sampled from a large, tertiary care teaching hospital in the United States. Echocardiographic findings are unlikely to aid in the differentiation between DCM and FDCM. Detailed pedigree analysis can successfully identify undiagnosed FDCM and should be encouraged prior to transplant listing as it has important implications for early detection and treatment of disease in family members. PMID- 26852067 TI - A Predictive Model for the Diagnosis of Allergic Drug Reactions According to the Medical History. AB - BACKGROUND: Quantification of the risk of an allergic drug reaction through the medical history is essential in clinical decision making. However, in normal clinical practice, this evaluation is generally entirely subjective. OBJECTIVE: The objective of this study was to construct a mathematical model to predict the risk of allergic drug reactions using the data collected in the medical history. METHODS: A total of 696 active principles, corresponding to 466 patients aged more than 14 years attending the Allergy Service of the University Hospital of Salamanca, were included. Simple binary logistic regression was used to determine associations between variables from the medical history and the final diagnosis, to construct a predictive model. RESULTS: Variables useful in predicting a final diagnosis of allergic drug reaction were age, sex, drug class, number of active principles, time to the reaction, number of doses, clinical presentation suggestive of allergic disease, and time to medical consultation. True adverse drug reactions were estimated to occur in 20% of active principles. However, possible allergic reactions could only be ruled out in 52.2%. CONCLUSIONS: The use of mathematical models could greatly improve the discriminatory capacity of the medical history. Both the overdiagnosis and underdiagnosis of allergic drug reactions should be considered a public health problem. PMID- 26852068 TI - A case of aquagenic urticaria successfully treated with omalizumab. PMID- 26852069 TI - Ovine secondary follicles vitrified out the ovarian tissue grow and develop in vitro better than those vitrified into the ovarian fragments. AB - Cryopreservation of preantral follicles is a promising technique to preserve female fertility. The aim of this study was to evaluate the effect of vitrification on the development of secondary follicles included in ovarian tissue or isolated after microdissection. An important end point included is the capacity of grown oocytes to resume meiosis. Sheep ovarian cortexes were cut into fragments and split into three different groups: (1) fresh (control): secondary follicles isolated without any previous vitrification; (2) follicle-vitrification (follicle-vit): secondary follicles vitrified in isolated form; and (3) tissue vitrification (tissue-vit): secondary follicles vitrified within fragments of ovarian tissue (in situ former) and subsequently subjected to isolation. From the three groups, isolated secondary follicles were submitted to IVC for 18 days. After IVC, cumulus-oocyte complexes (COCs) were harvested from follicles. As an additional control group, in vivo grown, in vivo-grown COCs were collected from antral ovarian follicles. All, recovered COCs were matured and the chromatin configuration was evaluated. Data were analyzed by ANOVA, and the means were compared by Student-Newman-Keuls test, and by chi-square. Differences were considered to be significant when P < 0.05. Isolated preantral follicles from all treatments had normal morphology, antrum formation, and low follicle degeneration after IVC. The growth rate between control and follicle-vit did not differ (P > 0.05), and was higher (P < 0.05) than for tissue-vit. The percentage of follicles that decreased diameter during IVC was significantly higher in tissue-vit than the in follicle-vit. Recovery rate of oocytes from normal follicles was higher in follicle-vit than in tissue-vit. Furthermore, oocyte viability was lower in tissue-vit than other treatments, and follicle-vit did not differ from control and in vivo grown. The percentage of oocytes meiosis resuming was not different between treatments except for in vivo grown. After vitrification, only follicle vit showed metaphase I oocyte. We conclude that secondary follicles vitrified after isolation displayed a better follicular growth rate, oocyte viability, percentage of oocytes reaching the metaphase I stage, and fewer follicles with decreased diameter after IVC. PMID- 26852070 TI - The activity of three glycosidases (beta-Nu-acetyloglucosaminidase, alpha mannosidase, and beta-galactosidase) in the follicular fluid and in the maturation medium affects bovine oocyte maturation. AB - We studied the role of follicular fluid's (FF) glycosidase (alpha-mannosidase [alpha-MUAlphaNu], beta-Nu-acetyloglucosaminidase [NAGASE], beta-galactosidase [beta-GAL]) activity during IVM of bovine oocytes. Oocytes were allocated into two groups according to the follicular size (small follicle [SF]: 2-5 mm, large follicle [LF]: >5-8 mm). In experiment 1, cumulus-oocyte complexes (COCs) quality was evaluated according to morphologic criteria (grades A, B-C, D); oocyte (n = 801) nuclear maturation was assessed after 24 hours of incubation. Bovine embryos were produced in vitro in groups (experiment 2, n = 1503 oocytes) or individually (experiment 3, n = 50 oocytes). More grade-A and -BC COCs were collected from SF and LF groups, respectively (P < 0.05). Maturation rate (experiment 1) and cleavage rate (experiments 2 and 3) were similar in SF and LF groups. Activity of all glycosidases in FF was higher (P < 0.05) in SF group than in LF group, whereas in maturation medium of SF group it was, overall, significantly lower than in that of LF (experiments 2 and 3). In FF of SF group, NAGASE positively associated with grade-A oocytes and negatively with BC oocytes; increased beta GAL was associated with degenerated oocytes. Cleavage rate in LF group, related negatively to NAGASE and positively to alpha-MAN in maturation medium. These results indicate that during maturation, COCs release NAGASE and consume beta GAL, but differences probably exist between individual and group maturation. PMID- 26852071 TI - Ventral Capsule/Ventral Striatum Deep Brain Stimulation Does Not Consistently Diminish Occipital Cross-Frequency Coupling. PMID- 26852072 TI - Reply to: Ventral Capsule/Ventral Striatum Deep Brain Stimulation Does Not Consistently Diminish Occipital Cross-Frequency Coupling. PMID- 26852073 TI - Therapeutic Potential of Cannabinoids in Psychosis. AB - Over recent years, the interest in the endocannabinoid system (ECS) as a new target for the treatment of schizophrenia has evolved. The ECS represents one of the most relevant neurotransmitter systems in the brain and mainly fulfills a homeostatic role in terms of neurotransmission but also with respect to inflammatory processes. Two main approaches to the modulation of endocannabinoid functioning have been chosen so far. First, the selective blockade or inverse agonism of the type 1 cannabinoid receptor has been tested for the improvement of acute psychotic symptoms, as well as for the improvement of cognitive functions in schizophrenia. This was not effective in either case. Second, the modulation of endocannabinoid levels by use of the phytocannabinoid cannabidiol and selective fatty acid amide hydrolase inhibitors has been proposed, and the antipsychotic properties of cannabidiol are currently being investigated in humans. Unfortunately, for most of these trials that have focused on psychopathological and cognitive effects of cannabidiol, no published data are available. However, there is first evidence that cannabidiol may ameliorate psychotic symptoms with a superior side-effect profile compared with established antipsychotics. In conclusion, several clinical trials targeting the ECS in acute schizophrenia have either been completed or are underway. Although publicly available results are currently limited, preliminary data indicate that selected compounds modulating the ECS may be effective in acute schizophrenia. Nevertheless, so far, sample sizes of patients investigated are not sufficient to come to a final judgment, and no maintenance studies are available to ensure long term efficacy and safety. PMID- 26852074 TI - Joan of Arc: Sanctity, witchcraft or epilepsy? AB - OBJECTIVE: The objective of this article is to describe whether Joan of Arc had epilepsy and how that may have influenced her sense of mission and ability to encourage thousands of people to help her to chase the English out of France. METHODS: Documentation of her Trial of Condemnation in 1431 provides a description of her episodes of experienced voices and visions. RESULTS: From the age of thirteen, Joan of Arc experienced frequent episodes of auditory hallucinations associated with elementary or complex visual hallucinations (e.g., a great light or human faces). These had sudden onset, lasting seconds or minutes at most, and occurred when awake or during sleep, arousing her. Some could be triggered by an auditory stimulus. She had no disorganized thought between the episodes. CONCLUSIONS: The semiology of the episodes is very suggestive of epileptic seizures, which have been considered as ecstatic by some authors or as partial epilepsy with auditory features by others, which seems more concordant with the ictal symptoms. The auditory and visual hallucinations could have had a religious content because during her childhood and adolescence, she was brought up in a religious environment, insomuch as this content first undefined only appeared after a few seizures. We can suppose that such hallucinations, without the knowledge of their medical origin, gave her a sense of divine mission, hence, a real strength to try to accomplish the orders she heard during the episodes. Her role during the Hundred Years' War and her narration of her strange episodes led her to be burned for heresy at the age of nineteen, yet rehabilitated 25 years later and to be canonized for her achievements in 1920. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". PMID- 26852075 TI - Phase 1b Study of Abiraterone Acetate Plus Prednisone and Docetaxel in Patients with Metastatic Castration-resistant Prostate Cancer. AB - : Coadministration of docetaxel and abiraterone acetate plus prednisone (AA + P) may benefit patients with metastatic castration-resistant prostate cancer (mCRPC) because of complementary mechanisms of action. COU-AA-206 was a phase 1b study to determine the safe dose combination of docetaxel and AA + P in three cohorts of chemotherapy-naive mCRPC patients. Twenty-two patients received escalating doses of docetaxel plus AA + P. The primary endpoint was the proportion of patients with a dose-limiting toxicity (DLT) between weeks 2 and 7. The recommended phase 2 dose (RP2D) was the highest safe combination of docetaxel plus AA + P. Prostate specific antigen (PSA) changes and intensive pharmacokinetic parameters for each drug were evaluated. Docetaxel 75mg/m2 + AA 1000mg + P 10mg was deemed the RP2D, with DLT in one of six patients. PSA declines from baseline of >=50% and >=90% were observed for 85.7% and 66.7% of patients, respectively. During median follow up of 14.5 mo, eight patients had PSA progression and six had radiographic progression or died. Systemic exposure was comparable for docetaxel and abiraterone when given alone or in combination. Studies are ongoing to confirm the efficacy of potent androgen receptor-targeted therapy plus taxane in early mCRPC. PATIENT SUMMARY: The combination of hormonal therapy and chemotherapy may improve outcomes in men with metastatic prostate cancer. This study demonstrates the ability to combine the hormonal therapy agent abiraterone acetate, plus prednisone, and the chemotherapy drug docetaxel with an acceptable side effect profile. A high rate of prostate-specific antigen decline was seen, but the study was small and additional research is needed before this becomes a standard approach. PMID- 26852076 TI - Reply to Yi Zhou, Weigang Yan, and Hanzhong Li's Letter to the Editor re: Eduard Baco, Erik Rud, Lars Magne Eri, et al. A Randomized Controlled Trial to Assess and Compare the Outcomes of Two-core Prostate Biopsy Guided by Fused Magnetic Resonance and Transrectal Ultrasound Images and Traditional 12-core Systematic Biopsy. Eur Urol 2016;69:149-56. PMID- 26852077 TI - Re: John P. Sfakianos, Eugene K. Cha, Gopa Iyer, et al. Genomic Characterization of Upper Tract Urothelial Carcinoma. Eur Urol 2015;68:970-7. PMID- 26852078 TI - Understanding cognitive processes behind acceptance or refusal of phase I trials. AB - Participation in phase I trials gives patients the chance to obtain control over their disease by trying an experimental therapy. The patients' vulnerability, the informed consent process aiming at understanding the purpose and potential benefits of the phase I trial, and the complexity of the studies may impact the patient's final decision. Emotionally difficult health conditions may induce patients to succumb to cognitive biases, allocating attention only on a part of the provided information. Filling the gap in patients' information process can foster the implementation of strategies to help physicians tailor clinical trials' communication providing personalized support and tailored medical information around patients' need, so avoiding cognitive biases in patients and improving informed shared decision quality. The aim of the present review article focuses on the analysis of cognitive and psychological factors that affect patients' decision to participate or not to early phase clinical trials. PMID- 26852079 TI - Resistance mechanisms after tyrosine kinase inhibitors afatinib and crizotinib in non-small cell lung cancer, a review of the literature. AB - Targeted treatment of advanced non-small cell lung cancer patients with afatinib in EGFR mutation or crizotinib in ALK break positive patients results in profound tumor responses but inevitably induces resistance. In this review we present currently known resistance mechanisms for afatinib and crizotinib two recently approved drugs. Resistance mechanisms identified for afatinib include c-MET amplification and the V843I EGFR mutation. Expression of FGFR1, increased IL6R/JAK/STAT signaling, enhanced interference with aerobic glycolysis and autophagy are associated with resistance to afatinib. Most common resistance mechanisms for ALK break positive cases are gatekeeper mutations in the ALK gene. Also activation of the EGFR pathway, KRAS mutations, the autophagy pathway and epithelial mesenchymal transition (EMT), have been associated with resistance. Many of the proposed resistance mechanisms need to be functionally studied to proof a causative relationship with resistance. PMID- 26852080 TI - Aboriginal and Torres Strait Islander women's experiences accessing standard hospital care for birth in South Australia - A phenomenological study. AB - BACKGROUND: Aboriginal and Torres Strait Islander women, hereafter called Indigenous women, can experience a lack of understanding of their cultural needs when accessing maternity care in the standard hospital care system. AIM: To explore the lived experiences described by Indigenous women accessing labour and birth care in the standard hospital care system at a tertiary public hospital in South Australia. METHODS: An interpretive Heideggerian phenomenological approach was used. Indigenous women who accessed standard care voluntarily agreed to participate in semi-structured interviews with Indigenous interviewers. The interviews were transcribed and analysed informed by van Manen's approach. FINDINGS: Thematic analysis revealed six main themes: "knowing what is best and wanting the best for my baby", "communicating my way", "how they made me feel", "all of my physical needs were met", "we have resilience and strength despite our hardships" and "recognising my culture". CONCLUSION: Indigenous women in this study expressed and shared some of their cultural needs, identifying culturally unsafe practices. Recommendations to address these include the extension of current care planners to include cultural needs; Aboriginal Maternal Infant Care (AMIC) workers for women from rural and remote areas; AMIC workers on call to assist the women and midwives; increased education, employment and retention of Indigenous midwives; increased review into the women's experiences; removal of signs on the door restricting visitors in the birth suite; flexibility in the application of hospital rules and regulations; and changes to birthing services in rural and remote areas so women may not have to relocate for birth. PMID- 26852081 TI - A response to the relationship between different types of sharps containers and Clostridium difficile infection rates in acute care hospitals. PMID- 26852082 TI - [Experimentation of an e-platform to detect situations at risk of cardiac impairment (platform E-care) in an internal medicine unit]. AB - INTRODUCTION: Monitoring patients with heart failure by telemedicine systems is a potential means susceptible to optimize the management of these patients and avoid life-threatening emergencies. In this context, we experimented in internal medicine unit an e-platform E-care dedicated to automated, intelligent detection of situations at risk of heart failure. METHODS: The E-care platform based on medical sensors (blood pressure, heart rate, O2, weight), communicating (Bluetooth), to go up, in real time, to an intelligent physiological information and an analysis of the ontology medical, leading ultimately to the generation of alerts. After a development phase (proof of concept), the E-care platform has been deployed and tested by health professionals and patients in an internal medicine unit with 20 beds, opened on emergencies to the Strasbourg University Hospitals. RESULTS: One hundred and eighty patients were included and 1500 measurements were obtained. The patient profile included in this experiment was an elderly patient, with comorbidity in 90% of cases, with a loss of autonomy in 25%. Health professionals were using E-care platform every day to their great satisfaction. This experiment made it possible to validate the technology choices, to consolidate the system, and to test the robustness of the platform E care. The collection continuously allowed us to have the critical number of patients for more detailed analysis of the relevance of alerts related to heart impairment. A preliminary analysis showed the relevance of the generated alerts. CONCLUSION: Preliminary results following the deployment of E-care platform in hospitals appear to show the relevance of technological choices, tools and solutions developed and adopted. This telemedicine system allows automatic, non intrusive, generate alerts related to the detection of situations at risk for heart failure. Ultimately, E-care was capable of preventing hospitalization. A home deployment is currently underway. PMID- 26852083 TI - [A digital ischemia of unusual cause]. PMID- 26852084 TI - Low dose tranexamic acid reduces blood transfusion rate after total knee arthroplasty: A population-based study in Taiwan. AB - BACKGROUND/PURPOSE: Previous reports, mostly small clinical trials conducted in USA or Europe, indicated that tranexamic acid (TXA) would be effective for reducing blood transfusions after total knee arthroplasty (TKA). However, large scale studies are needed regarding the effectiveness and safety issue of complication events following TKA, especially for the Asian population. We aimed to evaluate the efficacy and safety of TXA use based on data from an elderly population in Taiwan. METHODS: This was a retrospective population-based study using an inpatient dataset from the nationwide health insurance research database in Taiwan. Patients aged >65 years with a diagnosis of osteoarthritic knee in 2012 were included (n = 10,321). A low-dose intravenous form of TXA (250-1000 mg) was identified perioperatively during the TKA. The surgical outcomes of interest were allogeneic red blood cell transfusion and postoperative 30-day complications. RESULTS: A total of 1205 (11.7%) patients received TXA. Based on a multilevel logistic regression model, we found a 47% odds reduction of blood transfusion without elevating the complications of infection and vascular-related diseases. Furthermore, the drug effect in reducing transfusion was different among hospital levels, and medical centers had a relatively lower transfusion rate. CONCLUSION: The use of perioperative TXA was an efficient strategy to prevent blood loss after TKA. PMID- 26852085 TI - Cytomegalovirus-infected duodenal ulcer with severe recurrent bleeding. PMID- 26852087 TI - Lipid signaling in keratinocytes: Lipin-1 plays a PArt. PMID- 26852086 TI - Calcium channels: the potential therapeutic targets for inflammatory bone destruction of rheumatoid arthritis. AB - INTRODUCTION: Inflammatory bone resorption causes progressive joint destruction which ultimately leads to functional disability in rheumatoid arthritis (RA). The primary cell responsible for bone resorption is the osteoclast, which means it is a potential therapeutic target against bone destruction. In fact, experimental and clinical findings suggest that blockade of osteoclast differentiation and function is highly effective in inhibiting bone destruction in RA. DISCUSSION AND CONCLUSION: In this report, we show several lines of experimental evidence which suggest that a variety of Ca(2+) channels are essential in osteoclast differentiation and function, and present a hypothesis that modulation of Ca(2+) channels is a highly effective therapeutic strategy in preventing osteoclast induced structural damage in RA. PMID- 26852088 TI - The epidemiology of asthma and its comorbidities in Poland--Health problems of patients with severe asthma as evidenced in the Province of Lodz. AB - INTRODUCTION: Population studies supply interesting data regarding the epidemiology, comorbidity and risk factors of asthma, which have direct clinical implications for patients. OBJECTIVES: The aim of the work was to evaluate the degree of severity of asthma in the studied group, the levels of anti-asthma treatment, the prevalence of asthma comorbidities and their influence on the clinical course of the illness. PATIENTS AND METHODS: The study encompassed 451 participants: 52.11% were asthma patients (study group) and 47.89% were healthy subjects (controls). Respiratory function tests, ACTTM test and skin prick tests were performed. RESULTS: Asthma severity was mild in 14.89%, moderate in 49.36% and severe in 35.74%. Oral GCS were used by 29%, inhalers 44%, LABA 68%, SABA 67%, LAMA 6%, SAMA 14% and MX 16%. Rhinitis and allergy were significantly more common in patients. GERD and neurological diseases were risk factors for asthma, and GERD significantly intensified the risk of severe asthma. GERD, atherosclerosis, hypertension, ischaemic heart disease and other cardiac diseases, lipid disorders, COPD, and the presence of any neoplastic disease significantly worsened the degree of asthma control. DISCUSSION: Severe asthma was a significant clinical issue in over 35% of cases. The most commonly-used group of drugs were LABAs, while inhaled GCS and LAMA were uncommon, especially among severe cases. A significant problem was the high percentage of systemic GCS used by severe cases. The most important risk factor for asthma, including its severe form, is GERD. Numerous comorbid conditions significantly worsen the degree of asthma control. PMID- 26852089 TI - Isolation and characterization of wound-induced compounds from the leaves of Citrus hassaku. AB - Citrus plants are world widely cultivated as horticultural tree crops, and nowadays their pharmacological activities have been well studied. Since research of defense responses in citrus plants have been mainly focused on the post harvested fruits because of their commercial importance, defense mechanisms during their developmental stages have not been well understood. In the present study, two wound-induced compounds were isolated from leaves of Citrus hassaku, and their structures were elucidated by high-resolution electron spray ionization mass spectra (HRESIMS) and nuclear magnetic resonance (NMR) analyses. One of these compounds was identified as a known flavanone, hesperetin. The other was characterized as a novel furofuran lignan, and was named 'biscitrusnin-A'. Their antimicrobial activities were also evaluated. PMID- 26852090 TI - Optimization of a NH4PF6-enhanced, non-organic solvent, dual microextraction method for determination of phthalate metabolites in urine by high performance liquid chromatography. AB - In conventional ionic liquid-based dispersive liquid-liquid microextraction (IL DLLME) procedures, most of the IL disperser remains in the aqueous phase resulting in low recovery for moderately and weakly polar analytes due to the "carry-over effect". Herein, we successfully developed a "NH4PF6-enhanced, non organic solvent, dual microextraction" method (ANSDM) for pretreatment of phthalate (PAE) metabolites with weak to moderate polarity. This method utilized in situ reaction of NH4PF6 as an ion-exchange reagent and disperser to realize two microextractions after using [C8MIM]PF6 as an extraction solvent and [C4MIM]BF4 as a disperser for conventional DLLME. Single-factor experiments, a two-level full factorial experimental design and central composite design were applied for optimizing operational parameters using 3D response surfaces and contour lines. Under optimized conditions, the newly developed method provided high extraction recoveries (93.8-99.1%) and low LODs (ca. 0.3MUgL(-1)) for three phthalate metabolites in human urine. The primary advantages of the ANSDM method include: (1) integration of in situ reaction and conventional DLLME techniques to effectively extract both weak and moderately polar pollutants simultaneously; (2) non-organic solvent use in the microextraction procedure making the process safer and more environmental friendly; and (3) a time-saving, simple operation that is fully compatibility with HPLC analysis. To the best of our knowledge, our group is the first to develop the "non-organic solvent, dual microextraction" method and it has great potential as a sample pre-treatment technique for organic pollutants with weak to moderate polarity in biological and environmental matrices. PMID- 26852091 TI - Novel Zeb2 gene variation in the Mowat Wilson syndrome (MWS). AB - BACKGROUND: Mowat Wilson syndrome (MWS) is an uncommon association of Hirschsprung's disease (HSCR). Phenotypic features may develop with time, causing initial difficulties in diagnosis. MWS results from haploinsufficiency of the Zinc finger E-box-binding homeobox 2 (ZEB2) gene, and molecular diagnosis of ZEB2 mutation is required to confirm the diagnosis. We report the first confirmed cases of MWS in three children with the typical facial features, mental retardation, absent corpus callosum, epilepsy, and HSCR and novel Zeb2 variations on DNA analysis. METHODOLOGY: Clinical features were monitored. DNA extracted from peripheral blood was subjected to bidirectional sequencing analysis following PCR DNA amplification. ZEB2 gene results were compared to the ZEB2 reference sequence (ENS00000169554) for variation. Bioinformatic investigation of novel gene variants was via the "Blastx" program function available via the National Center for Biotechnology Information (http://www.bioinfo.org/NPInter/blast/blast_link.cgi). RESULTS: Clinical follow up showed that the phenotypic features were not all present at birth but developed with time in 2 surviving patients. Several Zeb2 variations were detected in the promoter region of the ZEB2 gene of which 2 were novel (-56A/T 1174 11A/12A). In addition, a novel heterozygous single nucleotide insertion in exon 2 of ZEB2 in one patient results in a frameshift causing deletion of the first 8 amino acids of the ZEB2 protein and an alteration of amino acids 9 (G9A), 11 (R11G), and 12 (C12A). In the third patient, a novel single nucleotide deletion exon 8 (1784delC Het) results in a frameshift at amino acid 595 of translated protein. This shortens protein from 1214 to 594 amino acids and affects the functionality of the critical ZEB2 protein. CONCLUSIONS: MWS is an important link to recognise clinically. It underlines the functionality of the Zeb2 gene in certain syndromic Hirschsprung's disease. These variations probably contribute to the clinical features of the Mowat Wilson phenotype in Hirschsprung's disease but should be confirmed in further research. PMID- 26852092 TI - Preoperative Distress Factors Predicting Postoperative Pain in Adolescents Undergoing Surgery: A Preliminary Study. AB - The purpose of this study was to determine if preoperative distress factors could be used as predictors of postoperative pain in adolescents scheduled for spinal fusion surgery. Patients reporting the presence of pain before surgery reported greater pain intensity at postoperative day (POD) 1 (p = .033), POD 2 (p = .008) and at follow-up 6 weeks after surgery (p = .0001). Preoperative trait anxiety was associated with pain intensity before surgery (p = .002) but not with postoperative pain intensity (p > .05). Salivary cortisol concentrations did not differentiate between anxious and nonanxious patients based on anxiety trait (p = .21) and was not associated with postoperative pain intensity (p > .05). These findings suggest that preoperative distress factors do not predict postoperative pain intensity in the acute and intermediate period. The presence of preoperative pain was the best predictor of postoperative pain intensity, suggesting that preoperative pain assessment will identify patients at an elevated risk for intense postoperative pain. PMID- 26852093 TI - Prevalence of psychiatric morbidity in the primary health clinic attendees in Kuwait. AB - BACKGROUND: A substantial proportion of primary clinic attendees suffer from psychiatric disorders and many of them are neither recognized nor adequately treated by primary clinic physicians. OBJECTIVES: To determine the point prevalence of, and identify risk factors for, depression, anxiety, and somatisation disorder in the primary health clinics in the country. METHOD: The Physical Health Questionnaires (PHQ-SADs), were administered to a randomized sample of 1046 primary clinic attendees in all the five governorates of the country over a 5-month period. The descriptive data were computed with chi-square tests while the association of demographic characteristics with psychiatric disorders was determined with the logistic regression test. RESULTS: 42.7% of the our patients suffered from psychiatric disorders including depressive (22.9%), anxiety (17.7%), and somatization (33.4%) disorder. Comorbidity between the three disorders was found in 20.4% of the sample; 11% had two and 10.4% had all three disorders. The Kuwaiti nationals, female gender, older age group subjects and those with lower level of education were more likely to suffer from psychiatric disorder. LIMITATIONS: The inter-rater reliability may have affected the results as large number of physicians were responsible for administering the questionnaires. Moreover, the study did not include eating and substance-abuse disorders and the findings were limited to detection of somatization, depression, and anxiety disorders. CONCLUSIONS: In order to ensure timely provision of appropriate treatment, the primary care physicians need adequate information on different forms of presentation, and basic front line treatment, of the common mental disorders at the primary care level. PMID- 26852094 TI - Cerebellar microstructural abnormalities in bipolar depression and unipolar depression: A diffusion kurtosis and perfusion imaging study. AB - BACKGROUND: Depression in the context of bipolar disorder (BD) is often misdiagnosed as unipolar depression (UD), leading to mistreatment and poor clinical outcomes. However, little is known about the similarities and differences in cerebellum between BD and UD. METHODS: Patients with BD (n=35) and UD (n=30) during a depressive episode as well as 40 healthy controls underwent diffusional kurtosis imaging (DKI) and three dimensional arterial spin labeling (3D ASL). The DKI parameters including mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr),fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr) and 3D ASL parameters (i.e. cerebral blood flow) was measured by using regions-of-interest (ROIs) analysis in the superior cerebellar peduncles (SCP), middle cerebellar peduncles (MCP) and dentate nuclei (DN) of cerebellum. RESULTS: Patients with UD exhibited significant differences from controls for DKI measures in bilateral SCP and MCP and cerebral blood flow (CBF) in bilateral SCP and left DN. Patients with BD exhibited significant differences from controls for DKI measures in the right MCP and left DN and CBF in the left DN. Patients with UD showed significantly lower MD values compared with patients with BD in the right SCP. Correlation analysis showed there were negative correlations between illness duration and MD and Dr values in the right SCP in UD. LIMITATIONS: This study was cross-sectional and the sample size was not large. Parts of the patients included were under medication prior to MRI scanning. CONCLUSIONS: Our findings provide new evidence of microstructural changes in cerebellum in BD and UD. The two disorders may have overlaps in microstructural abnormality in MCP and DN during the depressive period. Microstructural abnormality in SCP may be a key neurobiological feature of UD. PMID- 26852095 TI - Patients with a preference for medication do equally well in mindfulness-based cognitive therapy for recurrent depression as those preferring mindfulness. AB - BACKGROUND: Previous studies have suggested that patients' treatment preferences may influence treatment outcome. The current study investigated whether preference for either mindfulness-based cognitive therapy (MBCT) or maintenance antidepressant medication (mADM) to prevent relapse in recurrent depression was associated with patients' characteristics, treatment adherence, or treatment outcome of MBCT. METHODS: The data originated from two parallel randomised controlled trials, the first comparing the combination of MBCT and mADM to MBCT in patients preferring MBCT (n=249), the second comparing the combination to mADM alone in patients preferring mADM (n=68). Patients' characteristics were compared across the trials (n=317). Subsequently, adherence and clinical outcomes were compared for patients who all received the combination (n=154). RESULTS: Patients with a preference for mADM reported more previous depressive episodes and higher levels of mindfulness at baseline. Preference did not affect adherence to either MBCT or mADM. With regard to treatment outcome of MBCT added to mADM, preference was not associated with relapse/recurrence (chi(2)=0.07; p=.80), severity of (residual) depressive symptoms during the 15-month follow-up period (beta=-0.08, p=.49), or quality of life. LIMITATIONS: The group preferring mADM was relatively small. The influence of preferences on outcome may have been limited in the current study because both preference groups received both interventions. CONCLUSIONS: The fact that patients with a preference for medication did equally well as those with a preference for mindfulness supports the applicability of MBCT for recurrent depression. Future studies of MBCT should include measures of preferences to increase knowledge in this area. PMID- 26852096 TI - Removals of pharmaceutical compounds from hospital wastewater in membrane bioreactor operated under short hydraulic retention time. AB - Pilot-scale membrane bioreactor (MBR) was operated at a short hydraulic retention time (HRT) of 3 h for the treatment of hospital wastewater. The removals of eleven pharmaceutical compounds in MBR operated at different mixed liquor suspended solids (MLSS) level were investigated during which nitrification degree was differed. The results experiments revealed the importance of immediate adsorption onto the colloidal particles in supernatant of MBR sludge and subsequently removed by membrane filtration for the recalcitrant pharmaceutical compounds. Nevertheless, the removals through biodegradation during short HRT were also found significant for some compounds. DGGE profile revealed the development of pharmaceutical degrading microorganisms in MBR. PMID- 26852097 TI - Functionalized gold nanoparticles for topical delivery of methotrexate for the possible treatment of psoriasis. AB - Gold nanoparticles (AuNPs) represent an effective choice for topical drug delivery systems thanks to their small size, general non-toxicity, ease of functionalization and high surface to volume ratio. Even if systemic, methotrexate still plays an important role in psoriasis treatment: its topical use shows insufficient percutaneus penetration owing to limited passive diffusion, high molecular weight and dissociation at physiological pH. The aim of our study was to design a new drug delivery nanocarrier for Methotrexate and to improve its solubility, stability and biodistribution. AuNPs were on purpose prepared with a hydrophilic stabilizing layer, in order to improve the colloidal stability in water. Water-soluble gold nanoparticles functionalized by sodium 3 mercapto-1-propansulfonate (Au-3MPS) were prepared and loaded with methotrexate (MTX). The loading efficiency of MTX on Au-3MPS was assessed in the range 70-80%, with a fast release (80% in one hour). The release was studied up to 24h reaching the value of 95%. The Au-3MPS@MTX conjugate was fully characterized by spectroscopic techniques (UV-vis, FTIR) and DLS. Preliminary toxicity tests in the presence of keratinocytes monolayers allowed to assess that the used Au-3MPS are not toxic. The conjugate was then topically used on C57BL/6 mouse normal skin in order to trace the absorption behavior. STEM images clearly revealed the distribution of gold nanoparticles inside the cells. In vitro studies showed that Methotrexate conjugated with Au-3MPS is much more efficient than Methotrexate alone. Moreover, DL50, based on MTT analysis, is 20 folds reduced at 48 h, by the presence of nanoparticles conjugation. UV-vis spectra for in vivo tracing of the conjugate on bare mouse skin after 24h of application, show increased delivery of Methotrexate in the epidermis and dermis using Au-3MPS@MTX conjugate, compared to MTX alone. Moreover we observed absence of the Au-3MPS in the dermis and in the epidermis, suggesting that these layers of the skin do not retain the nanoparticles. Based on our data, we found that the novel Au-3MPS@MTX conjugate is an effective non-toxic carrier for the satisfactory percutaneous absorption of Methotrexate and could help in possible topical treatment of psoriasis. PMID- 26852098 TI - Cyclodextrin-assisted assembly of PEGylated polyester nanoparticles decorated with folate. AB - In the last decades, nano-oncologicals bearing a polyethylene glycol (PEG) coating are being emerging as biomimetic devices able to drive their drug cargo to solid tumors through passive mechanisms. To improve selectivity toward cancer cells, nanocarriers decorated with the small ligand folate have been widely investigated. Nevertheless, a great challenge remains the effective exposition of folate on nanoparticles (NPs), which is a key prerequisite to ensure the correct binding to receptor and the following endocytic uptake. On these premises, in this study we propose a novel strategy to produce core-shell folate-targeted NPs based on diblock copolymers of poly(epsilon-caprolactone) (PCL) and PEG through the aid of (2-hydroxypropyl)-beta-cyclodextrin (HPbetaCD). PCL4300-PEG2000 and PCL4300-PEG2000-Fol copolymers were synthesized, characterized and employed to produce NPs without and with HPbetaCD by a melting/sonication procedure. Colloidal properties of targeted NPs produced with HPbetaCD demonstrated a highly extended conformation of PEG chains in the shell, an enhanced interaction with a specific antibody against folate and a higher uptake in cells overexpressing folate receptor. Overall, these results suggest that proper manipulation of PEG shell conformation through HPbetaCD can represent a novel non-covalent strategy to modify shell features. PMID- 26852099 TI - Silver nanoparticles synthesized from Adenium obesum leaf extract induced DNA damage, apoptosis and autophagy via generation of reactive oxygen species. AB - Silver nanoparticles (AgNPs) are an important class of nanomaterial used for a wide range of industrial and biomedical applications. Adenium obesum is a plant of the family Apocynaceae that is rich in toxic cardiac glycosides; however, there is scarce information on the anticancer potential of its AgNPs. We herein report the novel biosynthesis of AgNPs using aqueous leaf extract of A. obesum (AOAgNPs). The synthesis of AOAgNPs was monitored by color change and ultraviolet visible spectroscopy (425 nm). It was further characterized by Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and transmission electron microscopy (TEM). The FTIR spectra for the AOAgNPs indicated the presence of terpenoids, long chain fatty acids, secondary amide derivatives and proteins that could be responsible for the reduction and capping of the formed AOAgNPs. X-ray diffraction confirmed the crystallinity of the AgNPs. The TEM images revealed mostly spherical particles in the size range of 10-30 nm. The biological properties of novel AOAgNPs were investigated on MCF-7 breast cancer cells. Cell viability was determined by the MTT assay. Generation of reactive oxygen species (ROS), DNA damage, induction of apoptosis and autophagy were assessed. A dose dependent decrease in the cell viability was observed. The IC50 value was calculated as 217 MUg/ml. Both qualitative and quantitative evaluation confirmed about a 2.5 fold increase in the generation of ROS at the highest concentration of 150 MUg/ml. A significant (p<0.05) increase in the DNA damage evaluated by comet assay was evident. Flow cytometry revealed an increase in the apoptotic cells (24%) in the AOAgNPs treated group compared to the control. Acridine orange staining of acidic vesicles in exposed cells confirmed the induction of autophagy. These findings suggest that AOAgNPs increased the level of ROS resulting in heightened the DNA damage, apoptosis and autophagy in MCF-7 cells. PMID- 26852100 TI - What the cell surface does not see: The gene vector under the protein corona. AB - The fate of lipid-based nanovectors, used in genetic targeting inside cells, depends on their behavior in biological media. In fact, during both in vitro and in vivo transfection, nanovectors come in contact with proteins that compete for their surface and build the protein corona, their true biological identity while engaging the cell membrane. Nonetheless, after cell internalization, the efficacy of transfection may depend also on structural modifications that occurred under the protein cover, following interaction with biological fluids. Here, based on previous in vivo experiments, two widely used lipid mixtures, namely DOTAP/DOPC and DC-Chol/DOPE, were identified as paradigms to investigate the impact of the inner structure of nanovectors on the transfection efficiency, all being proficiently internalized. The evolution of the inner structure of cationic lipoplexes and nanoparticles based on such lipid mixtures, following interaction with human plasma, could be unraveled. Particles were investigated in high dilution, approaching the biosimilar conditions. Data have demonstrated that the modulation of their inner structure depends on their lipid composition and the plasma concentration, still preserving the genetic payload. Interestingly, protein contact induces a variety of inner structures with different perviousness, including reshaping into cubic phases of different porosity, sometimes observed upon interaction between carrier-lipids and cell-lipids. Cubic reshaping is of biological relevance, as lipid cubic phases have been recently associated to both fusogenicity and to the readiness in releasing the payload to the final target via endosomal escape. PMID- 26852101 TI - Effect of surface potential on epithelial cell adhesion, proliferation and morphology. AB - Cell adhesion is the basis of individual cell survival, division and motility. Hence, understanding the effects that the surface properties have on cell adhesion, proliferation and morphology are crucial. In particular, surface charge/potential has been identified as an important factor that affects cell behavior. However, how cells respond to incremental changes in surface potential remains unclear. By using binary self-assembled monolayer (SAM) modified Au surfaces that are similar in mechanical/chemical properties and provide a series of surface potentials, the effect of surface potential on the behavior of cells can be studied. In this work, the effect of surface potential on epithelial cells, including human embryonic kidney (HEK293T) and human hepatocellular carcinoma (HepG2), were examined. The results showed that the adhesion density of epithelial cells increased with increasing surface potential, which is similar to but varied more significantly compared with fibroblasts. The proliferation rate is found to be independent of surface potential in both cell types. Furthermore, epithelial cells show no morphological change with respect to surface potential, whereas the morphology of the fibroblasts clearly changed with the surface potential. These differences between the cell types were rationalized by considering the difference in extracellular matrix composition. Laminin-dominant epithelial cells showed higher adhesion density and less morphological change than did fibronectin-dominant fibroblasts because the more significant adsorption of positively charged laminin on the surface enhanced the adhesion of epithelial cells. In contrast, due to the dominance of negatively charged fibronectin that adsorbed weakly on the surface, fibroblasts had to change their morphology to fit the inhomogeneous fibronectin-adsorbed area. PMID- 26852102 TI - Fabrication of composite poly(d,l-lactide)/montmorillonite nanoparticles for controlled delivery of acetaminophen by solvent-displacement method using glass capillary microfluidics. AB - Paracetamol (PCM)-loaded composite nanoparticles (NPs) composed of a biodegradable poly(d,l-lactide) (PLA) polymer matrix filled with organically modified montmorillonite (MMT) nanoparticles were fabricated by antisolvent nanoprecipitation in a microfluidic co-flow glass capillary device. The incorporation of MMT in the polymer improved both the drug encapsulation efficiency and the drug loading, and extended the rate of drug release in simulated intestinal fluid (pH 7.4). The particle size increased on increasing both the drug loading and the concentration of MMT in the polymer matrix, and decreased on increasing the aqueous to organic flow rate ratio. The drug encapsulation efficiency in the NPs was higher at higher aqueous to organic flow rate ratio due to faster formation of the NPs. The PCM-loaded PLA NPs containing 2 wt% MMT in PLA prepared at an aqueous to organic flow rate ratio of 10 with an orifice size of 200 MUm exhibited a spherical shape with a mean size of 296 nm, a drug encapsulation efficiency of 38.5% and a drug loading of 5.4%. The encapsulation of MMT and PCM in the NPs was confirmed by transmission electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and attenuated total reflection Fourier transform infrared spectroscopy. PMID- 26852103 TI - Click synthesis of quaternized poly(dimethylaminoethyl methacrylate) functionalized graphene oxide with improved antibacterial and antifouling ability. AB - A quaternized poly(dimethylaminoethyl methacrylate) functionalized graphene oxide (GO-QPDMAEMA) was successfully prepared in this study via click chemistry. Alkyne functionalized graphene oxide (GO-alkyne) was first synthesized through a two step amidation reaction of GO-COOH. Meanwhile, azide-terminated poly(dimethylaminoethyl methacrylate) (PDMAEMA-N3) was prepared via the atom transfer radical-polymerization of dimethylaminoethyl methacrylate (DMAEMA). Subsequently, PDMAEMA-N3 was grafted onto the GO-alkyne through click chemistry to obtain PDMAEMA modified graphene oxide (GO-PDMAEMA). Finally, the tertiary amino groups of GO-PDMAEMA were quaternized by ethyl bromide to provide a quaternized poly(dimethylaminoethyl methacrylate) functionalized graphene oxide (GO-QPDMAEMA). Various characterization techniques, including Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, UV-vis spectrometry, zeta potential, Raman, contact angle analyses and field emission scanning electron microscope were used to ascertain the successful preparation of the quaternized GO-QPDMAEMA. Furthermore, antibacterial and antifouling activities of GO-QPDMAEMA were investigated via protein adsorption, as well as bacterial and cell adhesion studies. The results suggest that the GO-QPDMAEMA surface exhibited significant antibacterial and antifouling properties, compared with the GO-COOH and GO-PDMAEMA surfaces. PMID- 26852105 TI - Improving antiproliferative effect of the anticancer drug cytarabine on human promyelocytic leukemia cells by coating on Fe3O4@SiO2 nanoparticles. AB - In this study, Fe3O4@SiO2-cytarabine magnetic nanoparticles (MNPs) were prepared via chemical coprecipitation reaction and coating silica on the surface of Fe3O4 MNPs by Stober method via sol-gel process. The surface of Fe3O4@SiO2 MNPs was modified by an anticancer drug, cytarabine. The structural properties of the samples were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Zetasizer analyzer, and transmission electron microscopy (TEM). The results indicated that the crystalline phase of iron oxide NPs was magnetite (Fe3O4) and the average sizes of Fe3O4@SiO2-cytarabine MNPs were about 23 nm. Also, the surface characterization of Fe3O4@SiO2-cytarabine MNPs by FT-IR showed that successful coating of Fe3O4 NPs with SiO2 and binding of cytarabine drug onto the surface of Fe3O4@SiO2 MNPs were through the hydroxyl groups of the drug. The in vitro cytotoxic activity of Fe3O4@SiO2-cytarabine MNPs was investigated against cancer cell line (HL60) in comparison with cytarabine using MTT colorimetric assay. The obtained results showed that the effect of Fe3O4@SiO2 cytarabine magnetic nanoparticles on the cell lines were about two orders of magnitude higher than that of cytarabine. Furthermore, in vitro DNA binding studies were investigated by UV-vis, circular dichroism, and fluorescence spectroscopy. The results for DNA binding illustrated that DNA aggregated on Fe3O4@SiO2-cytarabine MNPs via groove binding. PMID- 26852104 TI - Hyperbranched exopolysaccharide-enhanced foam properties of sodium fatty alcohol polyoxyethylene ether sulfate. AB - The foam properties, such as the foamability, foam stability, drainage, coalescence and bulk rheology, of aqueous solutions containing an eco-friendly exopolysaccharide (EPS) secreted by a deep-sea mesophilic bacterium, Wangia profunda SM-A87, and an anionic surfactant, sodium fatty alcohol polyoxyethylene ether sulfate (AES), were studied. Both the foamability and foam stability of the EPS/AES solutions are considerably higher than those of single AES solutions, even at very low AES concentrations, although pure EPS solutions cannot foam. The improved foamability and foam stability arise from the formation of the EPS/AES complex via hydrogen bonds at the interfaces. The synergism between the EPS and AES decreases the surface tension, increases the interfacial elasticity and water carrying capacity, and suppresses the coalescence and collapse of the foams. The EPS/AES foams are more salt-resistant than the AES foams. This work provides not only a new eco-friendly foam with great potential for use in enhanced oil recovery and health-care products but also useful guidance for designing other environmentally friendly foam systems that exhibit high performance. PMID- 26852106 TI - Tumor angiogenesis-related parameters in multi-phase enhanced CT correlated with outcomes of hepatocellular carcinoma patients after radical hepatectomy. AB - PURPOSE: To determine if the prognosis of hepatocellular carcinoma (HCC) patients after radical hepatectomy may be indicated by the degree and pattern of contrast enhancement on preoperative computed tomography (CT) scan of the tumor. MATERIALS: The degree and patterns of enhancement of HCC tumor images were retrospectively reviewed of 87 HCC patients who underwent preoperative contrast enhanced CT prior to radical hepatectomy. The patients' conditions and outcomes were followed after surgery. The Kaplan-Meier method and log-rank test were used for univariate survival analysis. The Cox proportional hazard method was performed for multivariate analysis. RESULTS: The 1- and 3-year cumulative survival rates of this cohort were 78% and 57%, respectively. The univariate analyses showed that risk factors contributing to survival were, in the arterial phase, the degree of tumor enhancement (A-dTE), tumor-to-aortic ratio (A-T/A), and tumor-to-liver CT value ratio (A-T/L); and in the portal venous phase, the tumor-to-aortic ratio (P-T/A), and tumor-to-liver ratio (P-T/L). Further multivariable Cox analysis revealed that the A-T/A (P = 0.020) and P-T/L (P = 0.045) were, independently, significant factors related to the survival rate. A T/A <0.25, P-T/L <0.85, or both predicted a poor outcome for HCC patients after radical hepatectomy. CONCLUSIONS: Preoperative multi-phase contrast-enhanced CT parameters could be helpful in the prognosis of HCC patents after radical hepatectomy. PMID- 26852107 TI - Volumetric breast density is essential for predicting cosmetic outcome at the late stage after breast-conserving surgery. AB - BACKGROUND: The critical issue related to breast-conserving therapy (BCT) is that cosmetic outcomes deteriorate with long-term follow-up. There is little research for breast density as a predictor of cosmetic outcomes at the late stage after BCT. To improve the long-term quality of life after BCT of breast cancer patients, the correlation of volumetric breast density (VBD) and cosmetic outcome at the late stage after BCT was evaluated. STUDY DESIGN: Breast volume, fibroglandular tissue volume, adipose tissue volume, and VBD were calculated on mammography using image analysis software (Volpara((r))) in 151 patients with BCT. Furthermore, the correlation of breast density and the change of breast volume over time was analyzed on mammography in 99 patients who were followed-up long-term after BCT. RESULTS: On multivariate analysis, VBD was a predictor of cosmetic outcome after BCT with percent breast volume excised (PBVE). Decreased adipose tissue volume and increased fibrosis were more common in patients with VBD < 15%. Furthermore, remnant breast volume continued to decrease over time in low breast density patients during long-term follow-up. 93% of patients with VBD >= 15% and PBVE < 10% had a better cosmetic outcome, while 60% of patients with VBD < 15% and PBVE >= 10% had a worse cosmetic outcome after BCT. CONCLUSIONS: While PBVE was involved in cosmetic outcome at the early stage after BCT, VBD was associated with cosmetic outcome at the late stage after BCT. Thus, a combination of VBD and PBVE could predict cosmetic outcome after BCT and contribute to the selection for the appropriate BCT. PMID- 26852108 TI - The contribution of stored malate and citrate to the substrate requirements of metabolism of ripening peach (Prunus persica L. Batsch) flesh is negligible. Implications for the occurrence of phosphoenolpyruvate carboxykinase and gluconeogenesis. AB - The first aim of this study was to determine the contribution of stored malate and citrate to the substrate requirements of metabolism in the ripening flesh of the peach (Prunus persica L. Batsch) cultivar Adriatica. In the flesh, stored malate accumulated before ripening could contribute little or nothing to the net substrate requirements of metabolism. This was because there was synthesis and not dissimilation of malate throughout ripening. Stored citrate could potentially contribute a very small amount (about 5.8%) of the substrate required by metabolism when the whole ripening period was considered, and a maximum of about 7.5% over the latter part of ripening. The second aim of this study was to investigate why phosphoenolpyruvate carboxykinase (PEPCK) an enzyme utilised in gluconeogenesis from malate and citrate is present in peach flesh. The occurrence and localisation of enzymes utilised in the metabolism of malate, citrate and amino acids were determined in peach flesh throughout its development. Phosphoenolpyruvate carboxylase (essential for the synthesis of malate and citrate) was present in the same cells and at the same time as PEPCK and NADP malic enzyme (both utilised in the dissimilation of malate and citrate). A hypothesis is presented to explain the presence of these enzymes and to account for the likely occurrence of gluconeogenesis. PMID- 26852109 TI - Changes in the protective mechanism of photosystem II and molecular regulation in response to high temperature stress in grapevines. AB - The response to high temperature stress, which influences the growth and development of grapes, varies between laboratory conditions and ambient growth conditions, and is poorly understood. In the present study, we investigated the effects of high temperature on grapevines (Vitis vinifera L. * Vitis labrusca L.) grown under artificial and ambient conditions. A temperature of 35 degrees C did not alter Photosystem II (PS II) activity and the expression of some heat-shock protein (HSPs) genes. These changes were, however, observed at 45 degrees C under artificial conditions, as well as when the ambient natural temperature was greater than 40 degrees C. Interestingly, these changes corresponded to shifts in PS II activity and HSPs expression. The protective mechanism of PS II was induced by temperatures greater than 40 degrees C. These data indicating that the expression of HSFA2, GLOS1 and some heat-shock protein (sHSPs) genes were more sensitive to the heat stress. Unlike the Kyoho grapevines, the Jumeigui grapevines showed rapid and dramatically deterioration in PS II activity and the expression of some heat response genes and HSP21, indicating that the Jumeigui grapevines could not counter the heat stress. These were some differences in PSII activity and the expression of heat response genes between the two cultivated conditions could be attributed to other environmental factors, inherent plant vigor, and the adaptation mechanism. PMID- 26852110 TI - Pre-existing CD19-independent GL7(-) Breg cells are expanded during inflammation and in mice with lupus-like disease. AB - Interleukin 10 (IL-10)-producing regulatory B-cells (Bregs) suppress inflammatory responses that mediate autoimmune diseases. However, it is unknown whether Bregs derive from a pre-existing dedicated B-cell lineage or if any B-cell can differentiate into Bregs in response to BCR or TLR activation. GL7(+) B-cells are antigen-experienced differentiated B-cells while GL7(-/lo) are at an early stage of B-cell differentiation. While both GL7(-/lo) and GL7(+) B cells can produce IL 10, differentiation of GL7(-) B-cells into Bregs does not require CD19- or Bcl6 induced signals, suggesting that BCR-induced proliferation or Ig class-switching is not necessary for generation of Breg cells. Of particular importance, we show that GL7(-) Breg cells are dramatically expanded in lupus-like mice and GL7(-) Bregs suppressed inflammatory responses in lupus-like mice by inducing expansion of Foxp3(+)Treg cells. Taken together, these results suggest that pre-existing GL7(-)IL-10(+) cells are expanded during inflammation, differentiate into GL7(+) Bregs and contribute to immune-regulation in lupus-like mice. PMID- 26852112 TI - Two rhodamine derived chemosensors excited by up-conversion lattice for cysteine detection: Synthesis, characterization and sensing behavior. AB - In this paper, two chemosensors derived from rhodamine were reported for cysteine optical recognition. An up-conversion NaYF4 lattice was applied as excitation host to minimize chemosensor photobleaching. This NaYF4 lattice was firstly modified with alpha-cyclodextrin, making it water dispersible. It was found that chemosensor absorption matched well with host emission. The energy transfer between this excitation host and our chemosensors was analyzed and confirmed by their spectral analysis and emission decay lifetime comparison. Detailed analysis suggested that the recognition mechanism between our chemosensors and cysteine was a simple one with binding stoichiometry of 1:1. Our chemosensors showed emission "off-on" effect towards cysteine with good photostability. Maximum sensitivity was obtained as 7.90 for our chemosensors with a linear working curve. S substituent was found positive to improve selectivity. PMID- 26852111 TI - The three-dimensional genome: principles and roles of long-distance interactions. AB - The linear sequence of eukaryotic genomes is arranged in a specific manner within the three-dimensional nuclear space. Interactions between distant sites partition the genome into domains of highly associating chromatin. Interaction domains are found in many organisms, but their properties and the principles governing their establishment vary between different species. Topologically associating domains (TADs) extending over large genomic regions are found in mammals and Drosophila melanogaster, whereas other types of contact domains exist in lower eukaryotes. Here we review recent studies that explore the mechanisms by which long distance chromatin interactions determine the 3D organization of the genome and the relationship between this organization and the establishment of specific patterns of gene expression. PMID- 26852113 TI - iEMG: Imaging electromyography. AB - Advanced data analysis and visualization methodologies have played an important role in making surface electromyography both a valuable diagnostic methodology of neuromuscular disorders and a robust brain-machine interface, usable as a simple interface for prosthesis control, arm movement analysis, stiffness control, gait analysis, etc. But for diagnostic purposes, as well as for interfaces where the activation of single muscles is of interest, surface EMG suffers from severe crosstalk between deep and superficial muscle activation, making the reliable detection of the source of the signal, as well as reliable quantification of deeper muscle activation, prohibitively difficult. To address these issues we present a novel approach for processing surface electromyographic data. Our approach enables the reconstruction of 3D muscular activity location, making the depth of muscular activity directly visible. This is even possible when deep muscles are overlaid with superficial muscles, such as seen in the human forearm. The method, which we call imaging EMG (iEMG), is based on using the crosstalk between a sufficiently large number of surface electromyographic electrodes to reconstruct the 3D generating electrical potential distribution within a given area. Our results are validated by in vivo measurements of iEMG and ultrasound on the human forearm. PMID- 26852114 TI - Neck and shoulder muscle activity and posture among helicopter pilots and crew members during military helicopter flight. AB - Neck pain among helicopter pilots and crew-members is common. This study quantified the physical workload on neck and shoulder muscles using electromyography (EMG) measures during helicopter flight. Nine standardized sorties were performed, encompassing: cruising from location A to location B (AB) and performing search and rescue (SAR). SAR was performed with Night Vision Goggles (NVG), while AB was performed with (AB+NVG) and without NVG (AB-NVG). EMG was recorded for: trapezius (TRA), upper neck extensors (UNE), and sternocleido mastoid (SCM). Maximal voluntary contractions (MVC) were performed for normalization of EMG (MVE). Neck posture of pilots and crew-members was monitored and pain intensity of neck, shoulder, and back was recorded. Mean muscle activity for UNE was ~10% MVE and significantly higher than TRA and SCM, and SCM was significantly lower than TRA. There was no significant difference between AB-NVG and AB+NVG. Muscle activity in the UNE was significantly higher during SAR+NVG than AB-NVG. Sortie time (%) with non-neutral neck posture for SAR+NVG and AB-NVG was: 80.4%, 74.5% (flexed), 55.5%, 47.9% (rotated), 4.5%, 3.7% (lateral flexed). Neck pain intensity increased significantly from pre- (0.7+/-1.3) to post-sortie (1.6+/-1.9) for pilots (p=0.028). If sustained, UNE activity of ~10% MVE is high, and implies a risk for neck disorders. PMID- 26852115 TI - Avian influenza infection dynamics under variable climatic conditions, viral prevalence is rainfall driven in waterfowl from temperate, south-east Australia. AB - Understanding Avian Influenza Virus (AIV) infection dynamics in wildlife is crucial because of possible virus spill over to livestock and humans. Studies from the northern hemisphere have suggested several ecological and environmental drivers of AIV prevalence in wild birds. To determine if the same drivers apply in the southern hemisphere, where more irregular environmental conditions prevail, we investigated AIV prevalence in ducks in relation to biotic and abiotic factors in south-eastern Australia. We sampled duck faeces for AIV and tested for an effect of bird numbers, rainfall anomaly, temperature anomaly and long-term ENSO (El-Nino Southern Oscillation) patterns on AIV prevalence. We demonstrate a positive long term effect of ENSO-related rainfall on AIV prevalence. We also found a more immediate response to rainfall where AIV prevalence was positively related to rainfall in the preceding 3-7 months. Additionally, for one duck species we found a positive relationship between their numbers and AIV prevalence, while prevalence was negatively or not affected by duck numbers in the remaining four species studied. In Australia largely non seasonal rainfall patterns determine breeding opportunities and thereby influence bird numbers. Based on our findings we suggest that rainfall influences age structures within populations, producing an influx of immunologically naive juveniles within the population, which may subsequently affect AIV infection dynamics. Our study suggests that drivers of AIV dynamics in the northern hemisphere do not have the same influence at our south-east Australian field site in the southern hemisphere due to more erratic climatological conditions. PMID- 26852116 TI - Removing and reimplanting deep brain stimulation therapy devices in resistant OCD (when the patient does not respond): case report. AB - BACKGROUND: Deep brain stimulation (DBS) is emerging as a promising tool in the treatment of refractory obsessive-compulsive disorder (OCD) but the search for the best target still continues. This issue is especially relevant when particularly resistant profiles are observed in some patients, which have been ascribed to individual responses to DBS according to differential patterns of connectivity. As patients have been implanted, new dilemmas have emerged, such as what to do when the patient does not respond to surgery. CASE PRESENTATION: Here we describe a 22-year-old male with extremely severe OCD who did not respond to treatment with DBS in the nucleus accumbens, but who did respond after explanting and reimplanting leads targeting the ventral capsule-ventral striatum region. Information regarding the position of the electrodes for both surgeries is provided and possible brain structures affected during stimulation are reviewed. To our knowledge this case is the first in the literature reporting the removal and reimplantation of DBS leads for therapeutical benefits in a patient affected by a mental disorder. CONCLUSION: The capability for explantation and reimplantation of leads should be considered as part of the DBS therapy reversibility profile in resistant mental disorders, as it allows application in cases of non-response to the first surgery. PMID- 26852117 TI - Multiple signaling factors and drugs alleviate neuronal death induced by expression of human and zebrafish tau proteins in vivo. AB - BACKGROUND: The axonal tau protein is a tubulin-binding protein, which plays important roles in the formation and stability of the microtubule. Mutations in the tau gene are associated with familial forms of frontotemporal dementia with Parkinsonism linked to chromosome-17 (FTDP-17). Paired helical filaments of tau and extracellular plaques containing beta-amyloid are found in the brain of Alzheimer's disease (AD) patients. RESULTS: Transgenic models, including those of zebrafish, have been employed to elucidate the mechanisms by which tau protein causes neurodegeneration. In this study, a transient expression system was established to express GFP fusion proteins of zebrafish and human tau under the control of a neuron-specific HuC promoter. Approximately ten neuronal cells expressing tau-GFP in zebrafish embryos were directly imaged and traced by time lapse recording, in order to evaluate the neurotoxicity induced by tau-GFP proteins. Expression of tau-GFP was observed to cause high levels of neuronal death. However, multiple signaling factors, such as Bcl2-L1, Nrf2, and GDNF, were found to effectively protect neuronal cells expressing tau-GFP from death. Treatment with chemical compounds that exert anti-oxidative or neurotrophic effects also resulted in a similar protective effect and maintained human tau-GFP protein in a phosphorylated state, as detected by antibodies pT212 and AT8. CONCLUSIONS: The novel finding of this study is that we established an expression system expressing tau-GFP in zebrafish embryos were directly imaged and traced by time-lapse recording to evaluate the neurotoxicity induced by tau-GFP proteins. This system may serve as an efficient in vivo imaging platform for the discovery of novel drugs against tauopathy. PMID- 26852118 TI - What is the value of reactive case detection in malaria control? A case-study in India and a systematic review. AB - BACKGROUND: Reactive case detection (RCD) for malaria is a strategy to identify additional malaria infections in areas of low malaria transmission and can complement passive surveillance. This study describes experiences with RCD in two Indian sites, and aimed to synthesize experiences with RCD across endemic countries. METHODS: RCD programmes were piloted in two urban areas of India with a low prevalence of mainly Plasmodium vivax malaria in 2014. Cases were identified in a clinic by microscopy and contacts were screened within 2 weeks; PCR, in addition to microscopy, was used to detect Plasmodium parasites. A systematic review was conducted to identify RCD experiences in the literature. RESULTS: In Chennai, 868 contacts were enrolled for 18 index cases of clinical malaria; in Nadiad, 131 contacts were enrolled for 20 index cases. No new malaria infections were detected in Nadiad among contacts, and four new infections were detected in Chennai (three P. vivax and one Plasmodium falciparum), of which two were among household members of index cases. An additional five studies describing results from an RCD strategy were identified in the literature: four in Africa and one in Thailand. Including the results from India, the average number of contacts screened per index case in a total of seven studies ranged from four to 50, and 126 in a case study in Thailand with one index case. Malaria was detected in 0-45 % of the contacted persons. The average number of index cases needed to be traced to find one new case of malaria ranged from one to five, and could not be assessed in one study in India (no contacts positive for 20 cases). Sharing the household with an index case was associated with a five fold increased risk of malaria compared to contacts from households without an index case (pooled risk ratio 5.29, 95 % CI 3.31-8.47, I(2) 0 %, four studies). CONCLUSIONS: RCD in areas of low malaria transmission is a labour-intensive strategy, and its benefit is not clear. Studies are needed to assess how RCD can be optimized or into alternatives where interventions are targeted to family members or hotspots. PMID- 26852119 TI - Glioblastoma multiform with ipsilateral carotid artery stenosis: carotid artery stent promote tumor growth? AB - BACKGROUND: Ischemic stroke and glioblastoma multiforme have similar features on anatomic magnetic resonance imaging (MRI) and thus may require a surgical biopsy for a definitive diagnosis. CASE PRESENTATION: A 55-year-old male complained of dysphasia for 4 weeks and continuous deterioration for 5 days. Cerebral infarction was considered based on MRI, which showed hyperintensity at the border zone of the left hemisphere, and computed tomography angiography (CTA) showed left carotid artery severe stenosis. The patient underwent placement of a left carotid artery stent, and his symptoms recurred 2 months after carotid artery stent (CAS). MRI showed multiple ring-enhanced lesions in the left temporal, parietal, and occipital lobes accompanied by massive brain edema. The final pathologic diagnosis was glioblastoma multiforme. CONCLUSION: Although there is no evidence that stent therapy for carotid artery stenosis will worsen an ipsilateral glioblastoma, we should be careful to perform surgeries involving carotid artery stents when the patient has a glioblastoma. PMID- 26852120 TI - Deubiquitination and the regulation of stress granule assembly. AB - Stress granules (SGs) are evolutionarily conserved ribonucleoprotein (RNP) structures that form in response to a variety of environmental and cellular cues. The presence of these RNP granules has been linked to a number of human diseases, including neurodegenerative disorders like amyotrophic lateral sclerosis (ALS) and spinocerebellar ataxia type 2 (Li et al., J Cell Biol 201:361-372, 2013; Nonhoff et al., Mol Biol Cell 18:1385-1396, 2007). Understanding how the assembly of these granules is controlled could, therefore, suggest possible routes of therapy for patients afflicted with these conditions. Interestingly, several reports have identified a potential role for protein deubiquitination in the assembly of these RNP granules. In particular, recent work has found that a specific deubiquitinase enzyme, Ubp3, is required for efficient SG formation in S. cerevisiae (Nostramo et al., Mol Cell Biol 36:173-183, 2016). This same enzyme has been linked to SGs in other organisms, including humans and the fission yeast, Schizosaccharomyces pombe (Takahashi et al., Mol Cell Biol 33:815-829, 2013; Wang et al., RNA 18:694-703, 2012). At first glance, these observations suggest that a striking degree of conservation exists for a ubiquitin-based mechanism controlling SG assembly. However, the devil is truly in the details here, as the precise nature of the involvement of this deubiquitinating enzyme seems to vary in each organism. Here, we briefly review these differences and attempt to provide an overarching model for the role of ubiquitin in SG formation. PMID- 26852121 TI - (Actino)Bacterial "intelligence": using comparative genomics to unravel the information processing capacities of microbes. AB - Bacterial genomes encode numerous and often sophisticated signaling devices to perceive changes in their environment and mount appropriate adaptive responses. With their help, microbes are able to orchestrate specific decision-making processes that alter the cellular behavior, but also integrate and communicate information. Moreover and beyond, some signal transducing systems also enable bacteria to remember and learn from previous stimuli to anticipate environmental changes. As recently suggested, all of these aspects indicate that bacteria do, in fact, exhibit cognition remarkably reminiscent of what we refer to as intelligent behavior, at least when referred to higher eukaryotes. In this essay, comprehensive data derived from comparative genomics analyses of microbial signal transduction systems are used to probe the concept of cognition in bacterial cells. Using a recent comprehensive analysis of over 100 actinobacterial genomes as a test case, we illustrate the different layers of the capacities of bacteria that result in cognitive and behavioral complexity as well as some form of 'bacterial intelligence'. We try to raise awareness to approach bacteria as cognitive organisms and believe that this view would enrich and open a new path in the experimental studies of bacterial signal transducing systems. PMID- 26852122 TI - Molecular docking of Glycine max and Medicago truncatula ureases with urea; bioinformatics approaches. AB - Urease (EC 3.5.1.5) is a nickel-dependent metalloenzyme catalyzing the hydrolysis of urea into ammonia and carbon dioxide. It is present in many bacteria, fungi, yeasts and plants. Most species, with few exceptions, use nickel metalloenzyme urease to hydrolyze urea, which is one of the commonly used nitrogen fertilizer in plant growth thus its enzymatic hydrolysis possesses vital importance in agricultural practices. Considering the essentiality and importance of urea and urease activity in most plants, this study aimed to comparatively investigate the ureases of two important legume species such as Glycine max (soybean) and Medicago truncatula (barrel medic) from Fabaceae family. With additional plant species, primary and secondary structures of 37 plant ureases were comparatively analyzed using various bioinformatics tools. A structure based phylogeny was constructed using predicted 3D models of G. max and M. truncatula, whose crystallographic structures are not available, along with three additional solved urease structures from Canavalia ensiformis (PDB: 4GY7), Bacillus pasteurii (PDB: 4UBP) and Klebsiella aerogenes (PDB: 1FWJ). In addition, urease structures of these species were docked with urea to analyze the binding affinities, interacting amino acids and atom distances in urease-urea complexes. Furthermore, mutable amino acids which could potentially affect the protein active site, stability and flexibility as well as overall protein stability were analyzed in urease structures of G. max and M. truncatula. Plant ureases demonstrated similar physico-chemical properties with 833-878 amino acid residues and 89.39-90.91 kDa molecular weight with mainly acidic (5.15-6.10 pI) nature. Four protein domain structures such as urease gamma, urease beta, urease alpha and amidohydro 1 characterized the plant ureases. Secondary structure of plant ureases also demonstrated conserved protein architecture, with predominantly alpha-helix and random coil structures. In structure-based phylogeny, plant ureases from G. max, M. truncatula and C. ensiformis were clearly diverged from bacterial ureases of B. pasteurii and K. aerogenes. Glu, Thr, His and Gly were commonly found as interacting residues in most urease-urea docking complexes while Glu was available in all docked structures. Besides, Ala and Arg residues, which are reported in active-site architecture of plant and bacterial ureases were present in G. max urea-urease complex but not present in others. Moreover, Arg435 and Arg437 in M. truncatula and G. max, respectively were identified as highly mutable hotspot residues residing in amidohydro 1 domain of enzyme. In addition, a number of stabilizing residues were predicted upon mutation of these hotspot residues however Cys and Thr made strong implications since they were also found in codon-aligned sequences as substitutions of hotspot residues. Comparative analyses of primary sequence and secondary structure in 37 different plants demonstrated quite conserved natures of ureases in plant kingdom. Structure-based phylogeny indicated the presence of a possible prokaryote-eukaryote split and implicated the subjection of bacterial ureases to heavy selection in prokaryotic evolution compared to plants. Urea-urease docking complexes suggested that different species could share common interacting residues as well as may have some other uncommon residues at species-dependent way. In silico mutation analyses identified mutable amino acids, which were predicted to reside in catalytic site of enzyme therefore mutagenesis at these sites seemed to have adverse effects on enzyme efficiency or function. This study findings will become valuable preliminary resource for future studies to further understand the primary, secondary and tertiary structures of urease sequences in plants as well as it will provide insights about various binding features of urea-urease complexes. PMID- 26852123 TI - Acute anuria after a family vacation to Corsica/France. AB - A 12-year-old male patient suffered hematuria. Histopathology of a biopsy showed granulomata suspicious for schistosomiasis. The patient had never travelled outside Europe during his entire lifetime. He had taken frequent bathes in various rivers during his last family holidays 5 months earlier in Corsica. Microfiltration of urine revealed viable ova of Schistosoma haematobium with alterated size and shape. Ultrasonography showed a large focal echopoor mass attached to the bladder roof. Four days after antihelminthic therapy, the patient suffered inferior abdominal pain and acute anuria. Ultrasound revealed an approximately 5-cm mass in the bladder lumen suspicious for a large blood clot. After taking non-invasive measures such as drinking high amounts of fluid and treating the lower abdomen with a warm water bag and massage, the clot was excreted with urine and symptoms subsided. The further course was uneventful until 11 months later when hematuria recurred. This time, parasitological urine examination confirmed non-viable schistosome ova. Hematuria was likely due to erosion of the bladder mucosa by calcified non-viable ova. PMID- 26852124 TI - Metabolic signatures of Besnoitia besnoiti-infected endothelial host cells and blockage of key metabolic pathways indicate high glycolytic and glutaminolytic needs of the parasite. AB - Besnoitia besnoiti is an obligate intracellular and emerging coccidian parasite of cattle with a significant economic impact on cattle industry. During acute infection, fast-proliferating tachyzoites are continuously formed mainly in endothelial host cells of infected animals. Given that offspring formation is a highly energy and cell building block demanding process, the parasite needs to exploit host cellular metabolism to meet its metabolic demands. Here, we analyzed the metabolic signatures of B. besnoiti-infected endothelial host cells and aimed to influence parasite proliferation by inhibitors of specific metabolic pathways. The following inhibitors were tested: fluoro 2-deoxy-D-glucose and 2-deoxy-D glucose (FDG, DG; inhibitors of glycolysis), 6-diazo-5-oxo-L-norleucin (DON; inhibitor of glutaminolysis), dichloroacetate (DCA; inhibitor of pyruvate dehydrogenase kinase which favorites channeling of glucose carbons into the TCA cycle) and adenosine-monophosphate (AMP; inhibitor of ribose 5-P synthesis). Overall, B. besnoiti infections of bovine endothelial cells induced a significant and infection rate-dependent increase of glucose, lactate, glutamine, glutamate, pyruvate, alanine, and serine conversion rates which together indicate a parasite triggered up-regulation of glycolysis and glutaminolysis. Thus, addition of DON, FDG, and DG into the cultivation medium of B. besnoiti infected endothelial cells led to a dose-dependent inhibition of parasite replication (4 MUM DON, 99.5 % inhibition; 2 mM FDG, 99.1 % inhibition; 2 mM DG, 93 % inhibition; and 8 mM DCA, 71.9 % inhibition). In contrast, AMP had no significant effects on total tachyzoite production up to a concentration of 20 mM. Together, these data may open new strategies for the development of therapeutics for B. besnoiti infections. PMID- 26852125 TI - PCR-RFLP method to detect zoonotic and host-specific Giardia duodenalis assemblages in dog fecal samples. AB - Giardia duodenalis is a zoonotic protozoan that parasitizes the upper small intestine of human and many mammals including dogs. To develop a restriction fragment length polymorphism (RFLP) method for typing zoonotic (A, B) and host specific (C, D) assemblages of G. duodenalis from dog, beta-giardin gene was amplified with design primer pairs B3 and B4. The PCR products were digested with restriction enzyme Afa I and Msp I; then, PCR-RFLP method was compared with HRM genotyping and sequencing method for G. duodenalis from dog. The results showed that each of assemblages A-D had unique restriction pattern, which was consistent with the predictive results. Among 21 samples tested by PCR-RFLP, 1 human-derived and 8 dog-derived G. duodenalis were identified as assemblage A; 5 dog-derived G. duodenalis as assemblage C; 7 dog-derived G. duodenalis as assemblage D, which were coincided with the HRM genotyping and sequencing results. It is concluded that the PCR-RFLP is quick, easy, and accurate method for the sequence typing of G. duodenalis zoonotic and specific assemblages from dogs. PMID- 26852126 TI - Ivermectin-loaded lipid nanocapsules: toward the development of a new antiparasitic delivery system for veterinary applications. AB - Ivermectin (IVM) is probably one of the most widely used antiparasitic drugs worldwide, and its efficacy is well established. However, slight differences in formulation may change the plasma kinetics, the biodistribution, and in consequence, the efficacy of this compound. The present study focuses on the development of a novel nanocarrier for the delivery of lipophilic drugs such as IVM and its potential application in antiparasitic control. Lipid nanocapsules (LNC) were prepared by a new phase inversion procedure and characterized in terms of size, surface potential, encapsulation efficiency, and physical stability. A complement activation assay (CH50) and uptake experiments by THP-1 macrophage cells were used to assess the stealth properties of this nanocarrier in vitro. Finally, a pharmacokinetics and biodistribution study was carried out as a proof of concept after subcutaneous (SC) injection in a rat model. The final IVM-LNC suspension displayed a narrow size distribution and an encapsulation rate higher than 90 % constant over the evaluated time (60 days). Through flow cytometry and blood permanence measurements, it was possible to confirm the ability of these particles to avoid the macrophage uptake. Moreover, the systemic disposition of IVM in the LNC administered by the SC route was higher (p < 0.05) (1367 ng h/ml) compared to treatment with a commercial formulation (CF) (1193 ng.h/ml), but no significant differences in the biodistribution pattern were found. In conclusion, this new carrier seems to be a promising therapeutic approach in antiparasitic control and to delay the appearance of resistance. PMID- 26852127 TI - Arsenic Exposure in Children through Drinking Water in Different Districts of Sindh, Pakistan. AB - A cross sectional study has been conducted during 2007-2010 for the assessment of arsenic (As) contamination in drinking water, and its impact on the health of local public belongs to five districts of Sindh, Pakistan. The toxic risk assessment of As in different areas of Sindh province based upon its concentration in drinking water and scalp hair of boys and girls of age group 5 10 and 11-15 years. The total and inorganic As species in drinking water samples of four districts Hyderabad, Sukkur, Naushehro Firoze, Nawab shah, and Dadu were determined by advance pre-concentration methodologies. The resulting data indicated that the dominant inorganic As species in municipal treated (Hyaderabad) and hand pumps (Sukkur, Naushehro Firoze, Nawab shah and Dadu) water samples were arsenate (As(V)) and arsenite (As(III)), respectively. The total As concentrations in hand pumps water samples of Dadu district were 6.0- to 35-fold higher than the World Health Organization permissible limit of (10 MUg/L) for drinking water. Whereas, total As in hand pump water samples of Sukkur, Naushehro Firoze, and Nawab shah were found in the range of 26.0-98.2, 18.0-50.6, and 52.3 85.2 MUg/L, respectively. However, municipal treated water samples of Hyderabad were within recommended level (As <10 MUg/L). The content of total As in children of both genders and age group belonging to Sukkur, Naushehro Firoze, Nawab shah, and Dadu was found to be significantly high as compared to those children residing in Hyderabad district. The Pearson coefficient of correlation r values between As levels in hand pump water and scalp hair samples of children belonging to Sukkur, Naushehro Firoze, Nawab shah, and Dadu were observed in the range of 0.65-0.75, 0.75-0.82, 0.80-0.90, and 0.95-0.98, respectively. The results of As toxicity risk assessment based on hazard quotient indicated that Dadu district has high carcinogenic exposure risk for children. Moreover, it is concluded that the children consuming groundwater of Sukkur, Naushehro Firoze, Nawab shah, and Dadu districts of Sindh, Pakistan were at risk of chronic As toxicity in future. PMID- 26852129 TI - Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft fur Angewandte Humanpharmakologie e.V. (AGAH). PMID- 26852128 TI - Chemoradiotherapy for localized extranodal natural killer/T-cell lymphoma, nasal type, using a shrinking-field radiation strategy: multi-institutional experience. AB - PURPOSES: The prognosis of localized extranodal natural killer/T-cell lymphoma, nasal type (ENKTL), has improved with the development of chemoradiotherapy. However, conventional extended-field radiotherapy may cause optic disorders. Our group has employed smaller radiation fields in an attempt to avoid toxicity. The efficacy and toxicity of treatments were evaluated. MATERIALS AND METHODS: Chemoradiotherapy was delivered with a shrinking-field radiotherapy strategy. The endpoints of this study were overall survival (OS), local control (LC), progression-free survival (PFS), and toxicity. RESULTS: Fifteen patients with localized ENKTL were treated. After irradiation (median, 40 Gy) to the tumor plus a prophylactic volume, a reduced treatment volume to the tumor was boosted (median, 10 Gy). Twelve patients underwent chemoradiotherapy and 3 patients received radiotherapy alone. A complete response was achieved in 12 and a partial response in 3 patients. The 5-year OS, PFS, and LC rates were 80, 67, and 93 %, respectively. Distant recurrence occurred in 4 patients and locoregional and distant recurrence in 1 patient. Cataract (grade 3) and dry eye (grade 2) were observed as late adverse events in 1 patient each. CONCLUSIONS: Sufficiently high OS and LC were achieved with acceptable toxicities. Appropriate target volumes may be smaller with newer chemotherapy regimens. PMID- 26852130 TI - Tracking of the origin of recurrent mutations of the BRCA1 and BRCA2 genes in the North-East of Italy and improved mutation analysis strategy. AB - BACKGROUND: About 20 % of hereditary breast cancers are caused by mutations in BRCA1 and BRCA2 genes. Since BRCA1 and BRCA2 mutations may be spread throughout the gene, genetic testing is usually performed by direct sequencing of entire coding regions. In some populations, especially if relatively isolated, a few number of recurrent mutations is reported, sometimes caused by founder effect. METHODS: BRCA1 and BRCA2 screening for mutations was carried out on 1114 breast and/or ovarian cancer patients complying with the eligibility criteria for BRCA testing. Haplotype analysis was performed on the probands carrying recurrent mutations and their relatives, using two sets of microsatellite markers covering the BRCA1 (D17S588, D17S806, D17S902, D17S1325, D17S855, D17S1328, D17S800, and D17S250) and BRCA2 (D13S220, D13S267, D13S171, D13S1701, D13S1698, D13S260, D13S290, D13S1246) loci. The DMLE + 2.2 software was used to estimate the age of BRCA1 c.676delT and BRCA2 c.7806-2A > G. A multiplex PCR and two different primer extension assays were optimized and used for genotyping the recurrent mutations of the two genes. RESULTS: In the time frame of almost 20 years of genetic testing, we have found that five BRCA1 and three BRCA2 mutations are recurrent in a substantial subset of carriers from North-East Italy and neighboring Istria, where they represent more than 50 % of all mutations. Microsatellite analyses identified a common haplotype of different length for each mutation. Age estimation of BRCA1 c.676delT and BRCA2 c.7806-2A > G mutations revealed that they arose in the Friuli Venezia Giulia area about 86 and 94 generations ago, respectively. Suggestion of an association between BRCA2 c.7806-2A > G and risk of breast cancer in males has emerged. Finally, we developed a simple and efficient pre-screening test, performing an in-house primer extension SNaPshot(r) assay for the rapid identification of the eight recurrent mutations. CONCLUSIONS: Proofs of common ancestry has been obtained for the eight recurrent mutations. The observed genotype-phenotype correlation and the proposed rapid mutation detection strategy could improve the clinical management of breast and ovarian patients in North-East of Italy and neighboring geographic areas. PMID- 26852131 TI - Bridging the gap between science and policy: an international survey of scientists and policy makers in China and Canada. AB - BACKGROUND: Bridging the gap between science and policy is an important task in evidence-informed policy making. The objective of this study is to prioritize ways to bridge the gap. METHODS: The study was based on an online survey of high ranking scientists and policy makers who have a senior position in universities and governments in the health sector in China and Canada. The sampling frame comprised of universities with schools of public health and medicine and various levels of government in health and public health. Participants included university presidents and professors, and government deputy ministers, directors general and directors working in the health field. Fourteen strategies were presented to the participants for ranking as current ways and ideal ways in the future to bridge the gap between science and policy. RESULTS: Over a 3-month survey period, there were 121 participants in China and 86 in Canada with response rates of 30.0 and 15.9 %, respectively. The top strategies selected by respondents included focus on policy (conducting research that focuses on policy questions), science-policy forums, and policy briefs, both as current ways and ideal ways to bridge the gap between science and policy. Conferences were considered a priority strategy as a current way, but not an ideal way in the future. Canadian participants were more in favor of using information technology (web-based portals and email updates) than their Chinese counterparts. Among Canadian participants, two strategies that were ranked low as current ways (collaboration in study design and collaboration in analysis) became a priority as ideal ways. This could signal a change in thinking in shifting the focus from the "back end" or "downstream" (knowledge dissemination) of the knowledge transfer process to the "front end" or "upstream" (knowledge generation). CONCLUSIONS: Our international study has confirmed a number of previously reported priority strategies to bridge the gap between science and policy. More importantly, our study has contributed to the future work on evidence-based policy making by comparing the responses from China and Canada and the current and ideal way for the future. Our study shows that the concept and strategies of bridging the gap between science and policy are not static but varying in space and evolving over time. PMID- 26852132 TI - Downregulation of histone H2A and H2B pathways is associated with anthracycline sensitivity in breast cancer. AB - BACKGROUND: Drug resistance in breast cancer is the major obstacle to effective treatment with chemotherapy. While upregulation of multidrug resistance genes is an important component of drug resistance mechanisms in vitro, their clinical relevance remains to be determined. Therefore, identifying pathways that could be targeted in the clinic to eliminate anthracycline-resistant breast cancer remains a major challenge. METHODS: We generated paired native and epirubicin-resistant MDA-MB-231, MCF7, SKBR3 and ZR-75-1 epirubicin-resistant breast cancer cell lines to identify pathways contributing to anthracycline resistance. Native cell lines were exposed to increasing concentrations of epirubicin until resistant cells were generated. To identify mechanisms driving epirubicin resistance, we used a complementary approach including gene expression analyses to identify molecular pathways involved in resistance, and small-molecule inhibitors to reverse resistance. In addition, we tested its clinical relevance in a BR9601 adjuvant clinical trial. RESULTS: Characterisation of epirubicin-resistant cells revealed that they were cross-resistant to doxorubicin and SN-38 and had alterations in apoptosis and cell-cycle profiles. Gene expression analysis identified deregulation of histone H2A and H2B genes in all four cell lines. Histone deacetylase small-molecule inhibitors reversed resistance and were cytotoxic for epirubicin-resistant cell lines, confirming that histone pathways are associated with epirubicin resistance. Gene expression of a novel 18-gene histone pathway module analysis of the BR9601 adjuvant clinical trial revealed that patients with low expression of the 18-gene histone module benefited from anthracycline treatment more than those with high expression (hazard ratio 0.35, 95 % confidence interval 0.13-0.96, p = 0.042). CONCLUSIONS: This study revealed a key pathway that contributes to anthracycline resistance and established model systems for investigating drug resistance in all four major breast cancer subtypes. As the histone modification can be targeted with small-molecule inhibitors, it represents a possible means of reversing clinical anthracycline resistance. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00003012 . Registered on 1 November 1999. PMID- 26852134 TI - Paroxysmal nocturnal hemoglobinuria in the era of complement inhibition. PMID- 26852133 TI - Repellent and Attractive Effects of alpha-, beta-, and Dihydro-beta- Ionone to Generalist and Specialist Herbivores. AB - In plants, the oxidative cleavage of carotenoid substrates produces volatile apocarotenoids, including alpha-ionone, beta-ionone, and dihydro-beta-ionone, compounds that are important in herbivore-plant communication. For example, beta ionone is part of an induced defense in canola, Brassica napus, and is released following wounding by herbivores. The objectives of the research were to evaluate whether these volatile compounds would: 1) be released in higher quantities from plants through the over-expression of the carotenoid cleavage dioxygenase1 (CCD1) gene and 2) cause herbivores to be repelled or attracted to over-expressing plants relative to the wild-type. In vivo dynamic headspace collection of volatiles coupled with gas chromatography-mass spectrometry was used to determine volatile organic compounds (VOC) in the headspace of the Arabidopsis thaliana ecotype Columbia-0 (L.) over-expressing the AtCCD1 gene. The analytical method allowed the detection of beta-ionone in the Arabidopsis headspace where emission rates ranged between 2 and 5-fold higher compared to the wild type, thus corroborating the in vivo enhancement of gene expression. A two chamber choice test between wild type and AtCCD1 plants revealed that crucifer flea beetle Phyllotreta cruciferae (Goeze) adults were repelled by the AtCCD1 plants with the highest transcription and beta-ionone levels. alpha-Ionone and dihydro-beta ionone were not found in the headspace analysis, but solutions of the three compounds were tested in the concentration range of beta-ionone found in the Arabidopsis headspace (0.05 to 0.5 ng/MUl) in order to assess their biological activity with crucifer flea beetle, two spotted spider mite Tetranychus urticae (Koch), and silverleaf whiteflies Bemisia tabaci (Gennadius). Choice bioassays demonstrated that beta-ionone has a strong repellent effect toward both the flea beetle and the spider mite, and significant oviposition deterrence to whiteflies. In contrast, dihydro-beta-ionone had attractant properties, especially to the crucifer flea beetle, while alpha-ionone did not show any significant activity. These findings demonstrate how regulating genes of the carotenoid pathway can increase herbivore deterrent volatiles, a novel tool for insect pest management. PMID- 26852135 TI - Comment on 'Tumour necrosis factor-alpha plays a significant role in the Aldara induced skin inflammation in mice'. PMID- 26852136 TI - Ameliorative effects of Xue-Fu-Zhu-Yu decoction, Tian-Ma-Gou-Teng-Yin and Wen-Dan decoction on myocardial fibrosis in a hypertensive rat mode. AB - BACKGROUND: Xue-Fu-Zhu-Yu decoction (XFZYD), Tian-Ma-Gou-Teng-Yin (TMGTY) and Wen Dan decoction (WDD) are Chinese herbal formulas used to treat hypertension and cardiovascular diseases in traditional Chinese medicine (TCM). The goal of our study is to determine if XFZYD, TMGTY or WDD treatment ameliorated myocardial fibrosis in spontaneously hypertensive rats (SHRs) and to identify the mechanisms underlying any beneficial effects observed during the courses of the investigation. METHODS: Forty-five 12-week-old male spontaneously hypertensive rats and five age-matched male Wistar-Kyoto control rats were studied for 16 weeks. Each day 6 g?kg(-1) or 12 g?kg(-1) of XFZYD, TMGTY or WDD was orally administered at the indicated dose, and the systolic blood pressure (SBP) of all rats was measured using the tail-cuff method. Collagen levels were measured via hydroxyproline content assays and histological examination. Transforming growth factor beta-1 (TGF-beta1) protein levels were determined via immunhistochemical and Western blot analysis. TGF-beta1 mRNA levels were assessed using real-time reverse transcription polymerase chain reaction. RESULTS: Systolic blood pressure was unaffected, but collagen and TGF-beta1 levels in SHRs treated with captopril and XFZYD (12 g?kg(-1)) were significantly reduced when compared with untreated control SHRs. Administration of 12 g?kg(-1) XFZYD increased myocardial cell protection and decreased TGF-beta1 mRNA and protein expression when compared with the other SHR treatment groups. CONCLUSIONS: XFZYD treatment demonstrated a superior ability to reverse myocardial fibrosis when compared with WDD or TMGTY treatment in SHRs. XFZYD also decreased TGF-beta1 mRNA and protein expression, suggesting that the TGF-beta1 signaling pathway plays a role in the therapeutic effects of XFZYD treatment. PMID- 26852137 TI - MMSE and MoCA in Parkinson's disease and dementia with Lewy bodies: a multicenter 1-year follow-up study. AB - The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are the most commonly used scales to test cognitive impairment in Lewy body disease (LBD), but there is no consensus on which is best suited to assess cognition in clinical practice and most sensitive to cognitive decline. Retrospective cohort study of 265 LBD patients [Parkinson's disease (PD) without dementia (PDnD, N = 197), PD with dementia (PDD, N = 40), and dementia with Lewy bodies (DLB, N = 28)] from an international consortium who completed both the MMSE and MoCA at baseline and 1-year follow-up (N = 153). Percentage of relative standard deviation (RSD%) at baseline was the measure of inter-individual variance, and estimation of change (Cohen's d) over time was calculated. RSD% for the MoCA (21 %) was greater than for the MMSE (13 %) (p = 0.03) in the whole group. This difference was significant only in PDnD (11 vs. 5 %, p < 0.01), but not in PDD (30 vs. 19 %, p = 0.37) or DLB (15 vs. 14 %, p = 0.78). In contrast, the 1-year estimation of change did not differ between the two tests in any of the groups (Cohen's effect <0.20 in each group). MMSE and MoCA are equal in measuring the rate of cognitive changes over time in LBD. However, in PDnD, the MoCA is a better measure of cognitive status as it lacks both ceiling and floor effects. PMID- 26852138 TI - Methylphenidate and emotional-motivational processing in attention deficit/hyperactivity disorder. AB - In line with the assumption that emotional-motivational deficits are one core dysfunction in ADHD, in one of our previous studies we observed a reduced reactivity towards pleasant pictures in adult ADHD patients as compared to controls. This was indicated by a lack of attenuation of the startle reflex specifically during pleasant pictures in ADHD patients. The first choice medical agents in ADHD, methylphenidate (MPH), is discussed to normalize these dysfunctions. However, experimental evidence in the sense of double-blind placebo controlled study designs is lacking. Therefore, we investigated 61 adult ADHD patients twice, one time with placebo and one time with MPH with the same experimental design as in our study previously and assessed emotion processing during the presentation of pleasant, neutral and unpleasant pictures. We obtained startle reflex data as well as valence and arousal ratings in association with the pictures. As previously shown, ADHD patients showed a diminished startle attenuation during pleasant pictures while startle potentiation during unpleasant pictures was normal. Valence and arousal ratings unsuspiciously increased with increasing pleasantness and arousal of the pictures, respectively. There were no significant influences of MPH. The study replicates that ADHD patients show a reduced reactivity towards pleasant stimuli. MPH did not normalize this dysfunction. Possibly, MPH only influences emotions during more complex behavioural tasks that involve executive functions in adults with ADHD. Our results emphasize the importance for the use of double-blind placebo-controlled designs in psychopharmacological research. PMID- 26852139 TI - Amifampridine phosphate (Firdapse((r))) is effective and safe in a phase 3 clinical trial in LEMS. AB - OBJECTIVE: We evaluated the efficacy and safety of amifampridine phosphate (Firdapse((r))) for symptomatic treatment in Lambert-Eaton myasthenic syndrome (LEMS). METHODS: Phase 3, randomized, double-blind, study. Patients were treated initially with amifampridine phosphate for 7-91 days, followed by randomization to continue amifampridine phosphate for 14 days or placebo (7-day taper, 7-day placebo). The primary efficacy endpoints were changes from baseline at day 14 in Quantitative Myasthenia Gravis and Subject Global Impression scores. RESULTS: The coprimary efficacy end points and 1 of the secondary efficacy end points were met, showing a significant benefit of aminfampridine phosphate over placebo at Day 14. All 5 primary, secondary, and tertiary endpoints achieved statistical significance at Day 8. Amifampridine phosphate was well tolerated; the most common adverse events were oral and digital paresthesias, nausea, and headache. CONCLUSIONS: This study provides Class I evidence of efficacy of amifampridine phosphate as a symptomatic treatment for LEMS. PMID- 26852140 TI - Anticancer potential of pyrrole (1, 2, a) pyrazine 1, 4, dione, hexahydro 3-(2 methyl propyl) (PPDHMP) extracted from a new marine bacterium, Staphylococcus sp. strain MB30. AB - Marine bacterium, strain MB30 isolated from the deep sea sediment of Bay of Bengal, India, exhibited antimicrobial activity against human pathogenic bacteria. Based on the 16S rRNA sequence homology and subsequent phylogenetic tree analysis, the strain MB30 was identified as Staphylococcus sp. The bioactive metabolite produced by the strain MB30 was purified through silica gel column chromatography and preparative HPLC. Purified metabolite was further characterized by FT-IR, LC-MS and NMR analyses. On the basis of spectroscopic data, the metabolite was identified as pyrrole (1, 2, a) pyrazine 1, 4, dione, hexahydro 3-(2-methyl propyl) (PPDHMP). The PPDHMP exhibited in vitro anticancer potential against lung (A549) and cervical (HeLa) cancer cells in a dose dependent manner with the IC50 concentration of 19.94 +/- 1.23 and 16.73 +/- 1.78 MUg ml(-1) respectively. The acridine orange (AO)/ethidium bromide (EB) and 4,6 diamidino-2-phenylindole dihydrochloride (DAPI) staining of the IC50 concentration of PPDHMP-treated cancer cells exhibited an array of morphological changes such as nuclear condensation, cell shrinkage and formation of apoptotic bodies. The PPDHMP-treated cancer cells induced the progressive accumulation of fragmented DNA in a time-dependent manner. Based on the flow cytometric analysis, it has become evident that the compound was also effective in arresting the cell cycle at G1 phase. Further, the Western blotting analysis confirmed the down regulation of cyclin-D1, cyclin dependent kinase (CDK-2), anti-apoptotic Bcl-2 family proteins (Bcl-2 and Bcl-xL), activation of caspase-9 and 3 with the cleavage of PARP. The PPDHMP-treated cancer cells also showed the inhibition of migration and invasive capacity of cancer cells. In the present investigation, for the first time, we have reported the extraction, purification and characterization of an anticancer metabolite, PPDHMP from a new marine bacterium, Staphylococcus sp. strain MB30. PMID- 26852143 TI - Acrylic bone cement in total joint arthroplasty: A review. AB - Acrylic bone cement has a variety of applications in orthopedic surgery. Primary uses in total arthroplasties are limited to prostheses fixation and antibiotic delivery. With the large number of total joint arthroplasties expected to continue to rise, understanding the role bone cement plays in the success of total joint arthroplasty can have a significant impact on daily practice. The literature is inconclusive on whether cemented or cementless fixation technique is superior, and choice of fixation type is mainly determined by surgeon preference and experience. Surgeons should understand that if poor techniques exist, short-term outcomes of the replaced joint may be at risk. Statement of clinical significance: This article attempts to clarify some points of bone cement use through a review of the mechanical properties related to bone cement, a comparison to alternative materials, influence of additives, and the effects on surgical outcomes. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:737-744, 2016. PMID- 26852142 TI - Impact of data resolution on three-dimensional structure inference methods. AB - BACKGROUND: Assays that are capable of detecting genome-wide chromatin interactions have produced massive amount of data and led to great understanding of the chromosomal three-dimensional (3D) structure. As technology becomes more sophisticated, higher-and-higher resolution data are being produced, going from the initial 1 Megabases (Mb) resolution to the current 10 Kilobases (Kb) or even 1 Kb resolution. The availability of genome-wide interaction data necessitates development of analytical methods to recover the underlying 3D spatial chromatin structure, but challenges abound. Most of the methods were proposed for analyzing data at low resolution (1 Mb). Their behaviors are thus unknown for higher resolution data. For such data, one of the key features is the high proportion of "0" contact counts among all available data, in other words, the excess of zeros. RESULTS: To address the issue of excess of zeros, in this paper, we propose a truncated Random effect EXpression (tREX) method that can handle data at various resolutions. We then assess the performance of tREX and a number of leading existing methods for recovering the underlying chromatin 3D structure. This was accomplished by creating in-silico data to mimic multiple levels of resolution and submit the methods to a "stress test". Finally, we applied tREX and the comparison methods to a Hi-C dataset for which FISH measurements are available to evaluate estimation accuracy. CONCLUSION: The proposed tREX method achieves consistently good performance in all 30 simulated settings considered. It is not only robust to resolution level and underlying parameters, but also insensitive to model misspecification. This conclusion is based on observations made in terms of 3D structure estimation accuracy and preservation of topologically associated domains. Application of the methods to the human lymphoblastoid cell line data on chromosomes 14 and 22 further substantiates the superior performance of tREX: the constructed 3D structure from tREX is consistent with the FISH measurements, and the corresponding distances predicted by tREX have higher correlation with the FISH measurements than any of the comparison methods. SOFTWARE: An open-source R package is available at http://www.stat.osu.edu/~statgen/Software/tRex. PMID- 26852144 TI - Development of the Neonatal Intestinal Microbiome and Its Association With Necrotizing Enterocolitis. AB - PURPOSE: Neonatal necrotizing enterocolitis (NEC) remains the most devastating gastrointestinal disease for premature infants. In the United States alone, NEC affects >4000 premature infants yearly, has a mortality rate of nearly 33%, and costs the health care system >$1 billion annually. Although NEC has been actively researched for several decades, its pathophysiology remains elusive. One potential mechanism suggests that disruption of the normal neonatal intestinal bacterial flora induces a proinflammatory state, allowing translocation of pathogens across the intestinal epithelia. Disruption of the normal intestinal flora (dysbiosis) is associated with many human diseases. Thus, it is a reasonable hypothesis that dysbiosis may play an important role in the development of NEC. This hypothesis is supported by evidence that probiotic use in premature infants can prevent the development of NEC. Although the role of probiotics and NEC is covered in other reviews, this review instead focuses on normal bacterial colonization in both term and preterm infants and on the association of dysbiosis and the development of NEC. METHODS: PubMed was queried with the use of the following key search terms: NEC, neonatal microbiome, fetal microbiome, maternal microbiome, neonatal dysbiosis, and microbiome ontogeny. Relevant literature was reviewed and selected for inclusion in accordance with the objectives of the article according to the authors' discretion. Articles that made key salient points in review articles were further pulled from PubMed. FINDINGS: Although the onset of NEC is thought to involve bacteria, the mechanisms behind their involvement remain unclear. Research to date has failed to identify a single causative organism, and current theories and data now indicate that a disruption of the host intestinal flora is associated with the onset of disease. Recent reports have found that a bloom of Proteobacteria, specifically Enterobacteriacae species, occurs just before the diagnosis of NEC. Whether this is a causative event or merely a marker of intestinal disease is still unclear. IMPLICATIONS: Because of the complexity of these interactions, it is vital that we continue to investigate the host-bacterial axis in the developing intestine in both humans and in animal models. PMID- 26852145 TI - Preface. Analytical chemistry for ADMET research: Recent advances and future directions in LC-MS/MS and omics approaches. PMID- 26852141 TI - Cellular apoptosis in the cardiorenal axis. AB - Cardiomyocyte apoptosis plays a pivotal role in the pathogenesis of heart failure. It may be induced by different stimuli, and it seems to be perpetuated by oxidative stress and inflammation. In this scenario, heart failure may trigger various cell-mediated and humoral pathways affecting distant organs, such as kidneys, contributing to higher therapeutic costs, morbidity and mortality. The term Cardiorenal Syndromes describes this condition and represents an important model for exploring the pathophysiology of cardiac and renal dysfunction. In this review, we have analyzed the mechanisms of organ interaction and the role of apoptosis in heart-kidney crosstalk, in particular its role in the pathogenesis of the different types of Cardiorenal Syndromes. PMID- 26852146 TI - Race and socioeconomic disparities in national stoma reversal rates. AB - BACKGROUND: Many temporary stomas are never reversed leading to significantly worse quality of life. Recent evidence suggests a lower rate of reversal among minority patients. Our study aimed to elucidate disparities in national stoma closure rates by race, medical insurance status, and household income. METHODS: Five years of data from the Nationwide Inpatient Sample (2008 to 2012) was used to identify the annual rates of stoma formation and annual rates of stoma closure. Stomas labeled as "permanent" or those created secondary to colorectal cancers were excluded. Temporary stoma closure rates were calculated, and differences were tested with the chi-square test. Separate analyses were performed by race/ethnicity, insurance status, and household income. Nationally representative estimates were calculated using discharge-level weights. RESULTS: The 5-year average annual rate of temporary stoma creation was 76,551 per year (46% colostomies and 54% ileostomies). The annual rate of stoma reversal was 50,155 per year that equated to an annual reversal rate of 65.5%. Reversal rates were higher among white patients compared with black patients (67% vs 56%, P < .001) and among privately insured patients compared with uninsured patients (88% vs 63%, P < .001). Reversal rates increased as the household income increased from 61% in the lowest income quartile to 72% in the highest quartile (P < .001). CONCLUSIONS: Stark disparities exist in national rates of stoma closure. Stoma closure is associated with race, insurance, and income status. This study highlights the lack of access to surgical health care among patients of minority race and low-income status. PMID- 26852147 TI - Survey of trauma surgeon practice of emergency department thoracotomy. AB - BACKGROUND: There continues to be significant debate in the trauma community regarding the indications for emergency department thoracotomy (EDT). Numerous studies have focused on the duration of arrest in EDT, whereas few have examined other factors that influence surgeon decision-making. We hypothesize that there is continued variability among surgeons in the use of EDT. METHODS: A 13-question web-based survey was distributed to the membership of a large, national trauma association, examining demographics, trauma fellowship completion, trauma center designation, professional organization membership, and annual EDTs performed. Consideration of patient's age, comorbidities, total injury burden, and the use of technological adjuncts-such as ultrasound-was assessed. Respondents were asked when they would perform the procedure after loss of vital signs for blunt and penetrating trauma. Logistic regression determined factors influencing consideration of EDT. RESULTS: Overall 540 of 1,485 surveys were completed (36.4%). Patient age, total injury burden, and comorbidities are considered by 38.5%, 29.1%, and 55.7% of respondents, respectively. Technological adjuncts are used always or most of the time by 64% of respondents. A majority of respondents (51.9%) would perform an EDT for penetrating trauma with loss of vital signs 5 to 10 minutes before arrival. For blunt trauma, the largest group of respondents (47.0%) would perform an EDT only when loss of vital signs occurred in the ED. In addition, 20.6% would never perform EDT for blunt traumatic arrest. CONCLUSIONS: EDT decision-making is more nuanced than previously described. Variation continues in the use of thoracotomy after loss of vital signs, in both blunt and penetrating trauma. For both mechanisms, there remains little consensus on the appropriate duration of arrest before performing EDT after arrest despite published guidelines. A large proportion of surgeons consider other factors such as patient age, total injury burden, and comorbidities in addition to vital signs when deciding to perform an EDT. Technological adjuncts are frequently used by surgeons to determine the need for EDT. PMID- 26852148 TI - A Review of Tooth Discoloration after Regenerative Endodontic Therapy. AB - INTRODUCTION: The American Association of Endodontists clinical considerations for regenerative therapy (April 2015) advise of the risk of the possible adverse effect of staining of teeth. It is widely acknowledged that before these guidelines were developed there was no standardized protocol for regenerative therapy, and different approaches using different materials have been reported. The purpose of this review was to undertake a systematic review of published cases to determine the incidence of reported discoloration and examine whether there was any particular association with any material. METHODS: A PubMed search was performed using key words for regenerative endodontic therapy consistent with prior published systematic reviews. RESULTS: There were 80 studies identified with 379 teeth treated. Many of the studies did not report on the presence or absence of discoloration. It was noted that there was a strong association of discoloration with the use of triple antibiotic paste containing minocycline; however, discoloration was also noted when other materials were used. Unfortunately, bleaching of stained teeth was not predictably achieved in some studies. CONCLUSIONS: The use of triple antibiotic paste with minocycline as the intracanal medicament should be reconsidered. Either calcium hydroxide or the double antibiotic paste of metronidazole and ciprofloxacin may limit discoloration. Mineral trioxide aggregate was also associated with discoloration. However, there is little evidence of an alternative superior material as a coronal barrier. Because discoloration is a patient-orientated outcome, further research should document and identify the incidence of discoloration in regenerative endodontic treatment. PMID- 26852150 TI - Turkmenistan bans tobacco sales. PMID- 26852149 TI - The Effect of Sodium Hypochlorite and Chlorhexidine as Irrigant Solutions for Root Canal Disinfection: A Systematic Review of Clinical Trials. AB - INTRODUCTION: This systematic review aimed to compare the effectiveness of sodium hypochlorite and chlorhexidine for root canal disinfection during root canal therapy. METHODS: A literature search for clinical trials was made on the PubMed (MEDLINE), Web of Knowledge, SCOPUS, and Science Direct databases and in the reference lists of the identified articles up to January 2015. Quality assessment of the selected studies was performed according to the Consolidated Standards of Reporting Trials statement. RESULTS: One clinical trial and 4 randomized clinical trials were selected from the 172 articles initially identified. There was heterogeneity in the laboratory methods used to assess the root canal disinfection as well as in the concentrations of the irrigants used. Therefore, meta-analysis was not performed. Two studies reported effective and similar reductions in bacterial levels for both irrigants. Sodium hypochlorite was more effective than chlorhexidine in reducing microorganisms in 1 study, and another reported opposite findings. Both root irrigants were ineffective in eliminating endotoxins from necrotic pulp root canals in 1 study. Trial design and information regarding randomization procedures were not clearly described in the clinical trials. No study compared laboratory results with clinical outcomes. CONCLUSIONS: The available evidence on this topic is scarce, and the findings of studies were not consistent. Additional randomized clinical trials using clinical outcomes to compare the use of sodium hypochlorite and chlorhexidine during root canal therapy are needed. PMID- 26852151 TI - [Hormonotherapy for breast cancer prevention: What about women with genetic predisposition to breast cancer?]. AB - In France, women carrying BRCA1/2 mutation, at an identified high risk of breast cancer are recommended to undergo breast MRI screening. That screening does not however prevent the risk of developing a breast cancer. The only alternative to breast cancer screening available in France is surgical prevention by prophylactic mastectomy. An interesting option for women who wish to reduce their breast cancer risk, but are unready for prophylactic mastectomy is a preventive hormonal treatment by aromatase inhibitors, or selective estrogens receptor modulators (SERMs). Reliable clinical trials show the efficiency of tamoxifen, raloxifen, exemestane, and anastrozole especially, in reducing breast cancer incidence by 33%, 34%, 65% and 53% respectively. This article tries to sum up the main published trials of breast cancer prevention with hormonal treatment, and presents the latest American and English clinical guidelines concerning hormonal prevention for women at high risk of breast cancer, and starts thinking about the possibilities of hormonoprevention, especially among women carrying a BRCA1/2 mutation in France. PMID- 26852152 TI - Neutrophil to lymphocyte ratio for evaluating the viscosity of otitis media with effusion: Which method has more benefit on clinic? PMID- 26852153 TI - Neutrophil to lymphocyte ratio for evaluating the viscosity of otitis media with effusion: A novel predictor or fad? PMID- 26852154 TI - Biological properties and therapeutic activities of honey in wound healing: A narrative review and meta-analysis. AB - For thousands of years, honey has been used for medicinal applications. The beneficial effects of honey, particularly its anti-microbial activity represent it as a useful option for management of various wounds. Honey contains major amounts of carbohydrates, lipids, amino acids, proteins, vitamin and minerals that have important roles in wound healing with minimum trauma during redressing. Because bees have different nutritional behavior and collect the nourishments from different and various plants, the produced honeys have different compositions. Thus different types of honey have different medicinal value leading to different effects on wound healing. This review clarifies the mechanisms and therapeutic properties of honey on wound healing. The mechanisms of action of honey in wound healing are majorly due to its hydrogen peroxide, high osmolality, acidity, non-peroxide factors, nitric oxide and phenols. Laboratory studies and clinical trials have shown that honey promotes autolytic debridement, stimulates growth of wound tissues and stimulates anti-inflammatory activities thus accelerates the wound healing processes. Compared with topical agents such as hydrofiber silver or silver sulfadiazine, honey is more effective in elimination of microbial contamination, reduction of wound area, promotion of re-epithelialization. In addition, honey improves the outcome of the wound healing by reducing the incidence and excessive scar formation. Therefore, application of honey can be an effective and economical approach in managing large and complicated wounds. PMID- 26852155 TI - [Weight and height local growth charts of Algerian children and adolescents (6-18 years of age)]. AB - Measurements of height and weight provide important information on growth and development, puberty, and nutritional status in children and adolescents. The aim of this study was to develop contemporary reference growth centiles for Algerian children and adolescents (6-18 years of age). A cross-sectional growth survey was conducted in government schools on 7772 healthy schoolchildren (45.1% boys and 54.9% girls) aged 6-18 years in Constantine (eastern Algeria) in 2008. Height and weight were measured with portable stadiometers and calibrated scales, respectively. Smooth reference curves of height and weight were estimated with the LMS method. These height and weight curves are presented together with local data from Arab countries and with the growth references of France, Belgium (Flanders), and the World Health Organization (WHO) 2007. In girls, median height and weight increased until 16 and 17 years of age, respectively, whereas in boys, they increased through age 18 years. Between ages 11 and 13 years (puberty), girls were taller and heavier than boys. After puberty, boys became taller than girls, by up to 13 cm by the age of 18 years. Median height and weight of Algerian boys and girls were generally intermediate between those observed in other Arab countries. They were higher than the French reference values up to the age of 13 years and lower than Belgian and WHO reference values at all ages. The present study provides Algerian height- and weight-for-age growth charts, which should be recommended as a national reference for monitoring growth and development in children and adolescents. PMID- 26852156 TI - Synthesis of ZnO nanowire arrays/3D graphene foam and application for determination of levodopa in the presence of uric acid. AB - Three-dimensional (3D) graphene foam (GF) was prepared by chemical vapor deposition (CVD) using nickel foam as the template. ZnO nanowire arrays (ZnO NWAs) were vertically grown on the 3D GF by hydrothermal synthesis to prepare ZnO NWAs/GF. This hybrid combines the properties of ZnO NWAs and 3D GF, which has favorable electrocatalysis and outstanding electrical conductivity. The vertically aligned ZnO NWAs grown on the GF enlarged the electroactive surface area, which was investigated from the Fe(CN)63-4+ redox kinetic study. The ZnO NWAs/GF was used as an electrochemical electrode for the determination of Levodopa (LD) in the presence of uric acid (UA). The electrochemical responses of the ZnO NWAs/GF electrode were investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The results show that the sensitivity of the electrode for LD is 3.15MUAMUM-1 in the concentration range of 0.05-20MUM and the measured detection limit of the electrode for LD is 50nM. The electrode also shows good selectivity, reproducibility and stability. The proposed electrode is succsefully used to determine LD in human plasma samples and it is potential for use in clinical research. PMID- 26852157 TI - Construction of single fluorophore ratiometric pH sensors using dual-emission Mn(2+)-doped quantum dots. AB - We present a novel ratiometric pH sensor design using water-soluble, dual emission, Mn(2+)-doped quantum dots (Qdots) decorated with D-penicillamine (DPA MnQdots). In contrast to more commonly used ratiometric pH sensors that rely on the coupling of two fluorophores, our design uses only a single emitter, which simplifies ratiometric sensing and broadens the applications of the sensor. Our single-emitter DPA-MnQdots exhibit two emission bands, at 510nm (green) and 610nm (red), which are, respectively, attributable to exciton recombination and emission of the Mn(2+) dopants. The emission intensity ratio (I510/I610) of the DPA-MnQdots depends linearly on surrounding pH values within physiological conditions (from pH 4.5 to 8.5). Moreover, the biocompatible DPA-MnQdots were used for long-term monitoring of local pH values in HeLa cells. PMID- 26852159 TI - Fabrication of ciprofloxacin molecular imprinted polymer coating on a stainless steel wire as a selective solid-phase microextraction fiber for sensitive determination of fluoroquinolones in biological fluids and tablet formulation using HPLC-UV detection. AB - A molecularly imprinted polymer (MIP) fiber on stainless steel wire using ciprofloxacin template with a mild template removal condition was synthetized and evaluated for fiber solid phase microextraction (SPME) of fluoroquinolones (FQs) from biological fluids and pharmaceutical samples, followed by high performance liquid chromatography analysis with UV detection (HPLC-UV). The developed MIP fiber exhibited high selectivity for the analytes in complex matrices. The coating of the fibers were inspected using fourier transform infrared spectrophotometry, thermogaravimetric analysis, energy dispersive X-ray (EDX) spectroscopy as well as by scanning electron microscopy (SEM). The fiber shows high thermal stability (up to 300 degrees C), good reproducibility and long lifetime. The composite coating did not swell in organic solvents nor did it strip off from the substrate. It was also highly stable and extremely adherent to the surface of the stainless steel fiber. The fabricated fiber exclusively exhibited excellent extraction efficiency and selectivity for some FQs. The effective parameters influencing the microextraction efficiency such as pH, extraction time, desorption condition, and stirring rate were investigated. Under optimized conditions, the limits of detection of the four FQs ranged from 0.023 0.033 MUg L(-1) (S/N=5) and the calibration graphs were linear in the concentration range from 0.1-40 MUg L(-1), the inter-day and intraday relative standard deviations (RSD) for various FQs at three different concentration level (n=5) using a single fiber were 1.1-4.4% and the fiber to fiber RSD% (n=5) was 4.3-6.7% at 5 MUg L(-1) of each anlyetes. The method was successfully applied for quantification of FQs in real samples including serum, plasma and tablet formulation with the recoveries between 97 to 102%. PMID- 26852160 TI - Pharmacokinetics of 21 active components in focal cerebral ischemic rats after oral administration of the active fraction of Xiao-Xu-Ming decoction. AB - The Xiao-Xu-Ming decoction (XXMD) is a traditional Chinese medicine prescription that is clinically used for the treatment of stroke. The active fraction of XXMD (AF-XXMD) exhibits pharmacological effects that are similar to those of XXMD. In this study, 21 primary compounds of AF-XXMD with potential anti-ischemic-stroke activities were selected as effective candidates to perform comparisons of their pharmacokinetic differences between control and cerebral ischemic rats and to characterize their pharmacokinetic behaviors in cerebral ischemic rats. After oral administration of AF-XXMD to control and cerebral ischemic rats, plasma and brain were harvested and analyzed using liquid chromatography coupled with tandem mass spectrometry. Reverse molecular docking results indicate that 21 AF-XXMD derived compounds exert potential neuroprotection, anti- inflammation, and vascular dilation effects via interaction with multiple targets in stroke-related pathways. The blood-brain permeability, cerebral exposure and brain region distribution of these compounds were found to change in cerebral ischemic models. Flavonoids were identified as the predominant form in plasma, whereas chromones were found to be the major form in the brain, and alkaloids possessed moderate blood-brain permeability. Collectively, the cerebral pharmacokinetic behaviors of chromones, flavonoids and alkaloids were found to change under pathological conditions. The efficacy of AF-XXMD against cerebral ischemia is relevant to the synergistic effects of these compounds in targeting different receptors and pathways. Chromones exhibit relatively high brain permeability, and their activity and mechanism warrant further investigation. PMID- 26852161 TI - Impurity profiling of L-methionine by HPLC on a mixed mode column. AB - Methionine is mostly produced synthetically. Thus, impurities are synthesis by products in addition to oxidation and dimerization products. Here, a sensitive HPLC method for the determination of impurities in L-methionine was developed and validated using a SIELC((r)) Primesep 100 column. Impurities were separated on the mixed mode column by reversed phase and cationic exchange mechanism. The limit of detection was in the range of 0.06-0.30 MUg/ml (0.0004-0.002%), limit of quantification in the range of 0.30-0.75 MUg/ml (0.002-0.005%) and linearity was shown in the range of 0.3-30.0 MUg/ml (0.002-0.200%). The method was found to be precise (intermediate precision RS <5%; n=2) and accurate (recovery 96.0-121.4%, n=3). The method is also suitable for the purity assessment of DL-methionine and D-methionine. The amount of impurities found in batches was very low. Only L methionine-sulfoxide and N-acetyl-DL-methionine could be detected in levels less than 0.05%. PMID- 26852162 TI - Mass spectrometry characterization of circulating human serum albumin microheterogeneity in patients with alcoholic hepatitis. AB - Human serum albumin (HSA) is the most abundant plasma protein, endowed with several biological properties unrelated to its oncotic power, such as antioxidant and free-radicals scavenging activities, binding and transport of many endogenous and exogenous substances, and regulation of endothelial function and inflammatory response. These non-oncotic activities are closely connected to the peculiarly dynamic structure of the albumin molecule. HSA undergoes spontaneous structural modifications, mainly by reaction with oxidants and saccharides; however, patients with cirrhosis show extensive post-transcriptional changes at several molecular sites of HSA, the degree of which parallels the severity of the disease. The present work reports the development and application of an innovative LC-MS analytical method for a rapid and reproducible determination of the relative abundance of HSA isoforms in plasma samples from alcoholic hepatitis (AH) patients. A condition of severe oxidative stress, similar to that observed in AH patients, is associated with profound changes in circulating HSA microheterogeneity. More interestingly, the high resolution provided by the analytical platform allowed the monitoring of novel oxidative products of HSA never reported before. PMID- 26852164 TI - The effects of future nationwide forest transition to discharge in the 21st century with regard to general circulation model climate change scenarios. AB - Forest disturbance (or land-cover change) and climatic variability are commonly recognised as two major drivers interactively influencing hydrology in forested watersheds. Future climate changes and corresponding changes in forest type and distribution are expected to generate changes in rainfall runoff that pose a threat to river catchments. It is therefore important to understand how future climate changes will effect average rainfall distribution and temperature and what effect this will have upon forest types across Japan. Recent deforestation of the present-day coniferous forest and expected increases in evergreen forest are shown to influence runoff processes and, therefore, to influence future runoff conditions. We strongly recommend that variations in forest type be considered in future plans to ameliorate projected climate changes. This will help to improve water retention and storage capacities, enhance the flood protection function of forests, and improve human health. We qualitatively assessed future changes in runoff including the effects of variation in forest type across Japan. Four general circulation models (GCMs) were selected from the Coupled Model Intercomparison Project Phase 5 (CMIP5) ensemble to provide the driving fields: the Model for Interdisciplinary Research on Climate (MIROC), the Meteorological Research Institute Atmospheric General Circulation Model (MRI GCM), the Hadley Centre Global Environment Model (HadGEM), and the Geophysical Fluid Dynamics Laboratory (GFDL) climate model. The simulations consisted of an ensemble including multiple physics configurations and different reference concentration pathways (RCP2.6, 4.5, and 8.5), the results of which have produced monthly data sets for the whole of Japan. The impacts of future climate changes on forest type in Japan are based on the balance amongst changes in rainfall distribution, temperature and hydrological factors. Methods for assessing the impact of such changes include the Catchment Simulator modelling frameworks based on the Minimal Advanced Treatments of Surface Interaction and Runoff (MATSIRO) model, which was expanded to estimate discharge by incorporating the effects of forest-type transition across the whole of Japan. The results indicated that, by the 2090s, annual runoff will increase above present-day values. Increases in annual variation in runoff by the 2090s was predicted to be around 14.1% when using the MRI-GCM data and 44.4% when using the HadGEM data. Analysis by long term projection showed the largest increases in runoff in the 2090s were related to the type of forest, such as evergreen. Increased runoff can have negative effects on both society and the environment, including increased flooding events, worsened water quality, habitat destruction and changes to the forest moisture retaining function. Prediction of the impacts of future climate change on water generation is crucial for effective environmental planning and management. PMID- 26852165 TI - Summary and synthesis of current knowledge. PMID- 26852163 TI - An Impaired Respiratory Electron Chain Triggers Down-regulation of the Energy Metabolism and De-ubiquitination of Solute Carrier Amino Acid Transporters. AB - Hundreds of genes have been associated with respiratory chain disease (RCD), the most common inborn error of metabolism so far. Elimination of the respiratory electron chain by depleting the entire mitochondrial DNA (mtDNA, rho(0) cells) has therefore one of the most severe impacts on the energy metabolism in eukaryotic cells. In this study, proteomic data sets including the post translational modifications (PTMs) phosphorylation and ubiquitination were integrated with metabolomic data sets and selected enzyme activities in the osteosarcoma cell line 143B.TK(-) A shotgun based SILAC LC-MS proteomics and a targeted metabolomics approach was applied to elucidate the consequences of the rho(0) state. Pathway and protein-protein interaction (PPI) network analyses revealed a nonuniform down-regulation of the respiratory electron chain, the tricarboxylic acid (TCA) cycle, and the pyruvate metabolism in rho(0) cells. Metabolites of the TCA cycle were dysregulated, such as a reduction of citric acid and cis-aconitic acid (six and 2.5-fold), and an increase of lactic acid, oxalacetic acid (both twofold), and succinic acid (fivefold) in rho(0) cells. Signaling pathways such as GPCR, EGFR, G12/13 alpha, and Rho GTPases were up regulated in rho(0) cells, which could be indicative for the mitochondrial retrograde response, a pathway of communication from mitochondria to the nucleus. This was supported by our phosphoproteome data, which revealed two main processes, GTPase-related signal transduction and cytoskeleton organization. Furthermore, a general de-ubiquitination in rho(0) cells was observed, for example, 80S ribosomal proteins were in average threefold and SLC amino acid transporters fivefold de-ubiquitinated. The latter might cause the observed significant increase of amino acid levels in rho(0) cells. We conclude that an elimination of the respiratory electron chain, e.g. mtDNA depletion, not only leads to an uneven down-regulation of mitochondrial energy pathways, but also triggers the retrograde response. PMID- 26852158 TI - Inflammation and its role in age-related macular degeneration. AB - Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms. PMID- 26852166 TI - Assessment of conjunctival goblet cell density using laser scanning confocal microscopy versus impression cytology. AB - PURPOSE: To determine the association between conjunctival goblet cell density (GCD) assessed using in vivo laser scanning confocal microscopy and conjunctival impression cytology in a healthy population. METHODS: Ninety (90) healthy participants undertook a validated 5-item dry eye questionnaire, non-invasive tear film break-up time measurement, ocular surface fluorescein staining and phenol red thread test. These tests where undertaken to diagnose and exclude participants with dry eye. The nasal bulbar conjunctiva was imaged using laser scanning confocal microscopy (LSCM). Conjunctival impression cytology (CIC) was performed in the same region a few minutes later. Conjunctival goblet cell density was calculated as cells/mm(2). RESULTS: There was a strong positive correlation of conjunctival GCD between LSCM and CIC (rho=0.66). Conjunctival goblet cell density was 475+/-41 cells/mm(2) and 466+/-51 cells/mm(2) measured by LSCM and CIC, respectively. CONCLUSIONS: The strong association between in vivo and in vitro cellular analysis for measuring conjunctival GCD suggests that the more invasive CIC can be replaced by the less invasive LSCM in research and clinical practice. PMID- 26852167 TI - Comparison of the change in posterior corneal elevation and corneal biomechanical parameters after small incision lenticule extraction and femtosecond laser assisted LASIK for high myopia correction. AB - PURPOSE: To compare posterior corneal elevation (PCE) changes and corneal biomechanical changes post fematosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE) procedures using the Pentacam system and the Ocular Response Analyzer (ORA). DESIGN: Retrospective observational case series study. METHOD: 106 patients with bilateral myopia who underwent either FS-LASIK (56 patients) or SMILE (50 patients) were reviewed, only the right eye was used in the analysis. Inclusion criteria include a spherical equivalent of -6.00DS and completion of 12 months follow up. The main outcome evaluated was change in PCE at 3 months, 6 months and 12 months post-operation using the Pentacam system. Corneal biomechanical parameters were evaluated at 6 and 12 months with the ORA. RESULTS: PCE change at 3 and 6 months were not significantly different between the two procedures (p=0.064, p=0.109 respectively). At 12 months, PCE change was greater in FS-LASIK than SMILE (p=0.048). One-way ANOVA showed that for either procedure, the change in PCE did not differ at 3, 6 or 12 months post operation. CH and CRF values were reduced after both procedures, with FS-LASIK demonstrating a greater reduction in CRF than SMILE at 6 and 12 months (p=0.037 and p=0.001). Both CH and CRF reduction correlated with PCE increase at 6 and 12 months. CONCLUSION: FS-LASIK demonstrated a greater increase in PCE than SMILE only at 12 months, as well as a greater reduction of CRF than SMILE. There were no significant differences in PCE change over time within either group. PMID- 26852168 TI - Association between microRNA polymorphisms and chronic pancreatitis. AB - BACKGROUD: MicroRNAs play important roles in the development and progression of many human diseases. mir-146a could significantly suppress the induction of proinflammatory cytokines IL-1beta, IL-6, TNF-alpha, NF-kappaB and chemokine MCP 1, which might play important roles in chronic pancreatitis. This study was conducted to evaluate the association between mir-146a rs2910164, a functional polymorphism in the pre-mir-146a, and chronic pancreatitis risk. METHODS: The rs2910164 genotypes were determined in 165 patients with chronic pancreatitis and 200 healthy controls who were frequency matched for age and gender. One single nucleotide polymorphism (rs2910164) was genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP). RESULTS: The frequency of individuals who carried [G] allele was significantly higher in cases (62.7%) than in controls (53.7%, p = 0.015), which resulted in a statistically significant pathogenic effect associated with this variant allele (OR: 1.448, CI: 1.076 1.950; p = 0.015). The GC and GG genotypes showed strong and significant increased risk for complication of chronic pancreatitis (OR = 3.668, 95%CI = 1.233-10.916, p = 0.019; OR = 5.667, 95%CI = 1.852-17.336, p = 0.002). The individuals carrying G allele confer a lower expression level of mature mir-146a. CONCLUSION: These findings suggest that the mir-146a rs2910164 may contribute to genetic susceptibility to chronic pancreatitis, and that mir-146a might be involved in chronic pancreatitis development. PMID- 26852169 TI - Prognostic impact of preoperative NLR and CA19-9 in pancreatic cancer. AB - BACKGROUND: Recently, several preoperative proinflammatory markers and nutritional factors such as neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) have been reported as significant predictor for poor prognosis of various malignant tumors. In this study, we evaluated the prognostic values of these preoperative parameters in patients with resectable pancreatic head cancer. METHODS: We retrospectively reviewed consecutive patients who underwent PD for pancreatic head cancer between 2007 and 2012. A total of 46 patients were enrolled in this analysis. Preoperative parameters such as CRP, CA19-9, NLR and PNI at the time of presentation were recorded as well as overall survival. Cancer specific survival was assessed using Kaplan-Meier method. Univariate and multivariate Cox regression models were applied to evaluate the prognostic relevance of preoperative parameters. The correlations between CA19-9 values, NLR and pathological findings, first recurrence site were respectively reviewed. RESULTS: In multivariable analysis preoperative high NLR (?2.7) and high CA19-9 (?230) were independent prognostic factors for poor survival (P value: 0.03 and 0.025, respectively). Kaplan-Meier survival analysis demonstrated the overall 2-year survival rate in patients with high NLR or high CA19-9 were 37.5% compared with 89.9% in patients with low NLR and low CA19-9. CONCLUSION: Preoperative NLR and serum CA19-9 offer significant prognostic information associated with overall survival following PD in the patients with pancreatic head cancer. PMID- 26852170 TI - Systematic review and meta-analysis on targeted therapy in advanced pancreatic cancer. AB - AIM: A systematic review and meta-analysis from literature has been performed to assess the impact of targeted therapy in advanced pancreatic cancer. METHODS: By searching different literature databases and major cancer meetings proceedings, data from all randomized clinical trials designed to investigate molecular targeted agents in the treatment of advanced pancreatic cancer were collected. The time-frame between January 2007 and March 2015 was selected. Data on predefined end-points, including overall survival, progression-free survival in terms of Hazard Ratio and response-rate were extracted and analyzed by a random effects model. Pooled data analysis was performed according to the DerSimonian and Laird test. The occurrence of publication bias was investigated through Begg's test by visual inspection of funnel plots. RESULTS: Twenty-seven randomized clinical trials for a total of 8205 patients were selected and included in the final analysis. A significant benefit was demonstrated for anti EGFR agents on overall survival (HR = 0.880; 95% confidence interval (CI) 0.797 0.972; p = 0.011). In the pooled analysis no benefit on overall survival (OS: pooled HR = 0.957; 95%CI 0.900-1.017; p = 0.153), or progression-free survival (PFS: pooled HR = 0.908; 95%CI 0.817-1.010; p = 0.075) for targeted-based therapies as compared to conventional treatments could be demonstrated. No advantage was reported in response-rate (OR for RR = 1.210; 95%CI 0.990-1.478; p = 0.063). Begg's funnel plot showed no evidence of publication bias. CONCLUSION: The use of molecular targeted agents does not translate into clinical benefit. Therefore, our work highlights the need to identify predictive factors for patient selection and rationally designed clinical trials. PMID- 26852171 TI - Tracking Animal Dispersal: From Individual Movement to Community Assembly and Global Range Dynamics. AB - Dispersal is one of the key processes in shaping distributional ranges and community assemblages, but we know little about animal dispersal at the individual, population, or community levels, or about how dispersal correlates with the establishment and colonization of new areas. This is largely due to difficulties in studying individual movements at the relevant spatiotemporal scale, leading to a gap between the direct study of dispersal and our understanding of the build-up of larger-scale biodiversity. Recent advances in tracking technology make it possible to bridge this gap. We propose a way to link movement, dispersal, ecology, and biogeography. In particular, we offer a framework to scale-up from processes at the individual level to global patterns of biodiversity. PMID- 26852172 TI - Underutilization of radiation therapy in early-stage marginal zone lymphoma negatively impacts overall survival. AB - PURPOSE: Multiple population-based studies have suggested increasing omission of radiation therapy in favor of alternative treatment strategies in lymphomas, with an associated negative impact on survival. Radiation therapy has long been considered the standard management for many mucosa-associated lymphoid tissue lymphomas. Thus, we aimed to evaluate patterns of treatment utilization and survival. METHODS AND MATERIALS: A retrospective analysis based on the National Cancer Database was performed on 22,378 patients with splenic, nodal, or extranodal stage I-II marginal zone lymphoma diagnosed between 1998 and 2012. A logistic regression model was used to assess the association between sociodemographic, tumor, and treatment characteristics and the utilization of radiation therapy. Multivariate propensity score-adjusted Cox proportional hazards models were performed to identify factors independently associated with overall survival (OS). RESULTS: Of 22,378 patients, 82% had stage I disease, 77% had extranodal mucosa-associated lymphoid tissue lymphoma, 5% had splenic marginal zone lymphoma, and 64% were older than 60 years. Radiation therapy utilization decreased from a peak of 39% in 2007 to 33% in 2011 (P < .001), with a corresponding significant increase in systemic therapy utilization. Radiation therapy was associated with a 5- and 10-year OS of 86.7% and 68.8% compared with 78.3% and 54.3% for no radiation therapy (P < .001). On multivariate propensity score-adjusted survival analysis, radiation therapy remained independently associated with improved OS (hazard of death, 0.75; 95% confidence interval, 0.65 0.85; P < .001). CONCLUSIONS: Although clinical guidelines endorse radiation therapy as the preferred initial therapy for early-stage nongastric and Helicobacter pylori-negative gastric mucosa-associated lymphoid tissue lymphoma, radiation therapy is underused. Radiation therapy with or without systemic therapy was associated with a significant improvement in OS and should remain standard of care. PMID- 26852173 TI - Margin reduction from image guided radiation therapy for soft tissue sarcoma: Secondary analysis of Radiation Therapy Oncology Group 0630 results. AB - PURPOSE: Six imaging modalities were used in Radiation Therapy Oncology Group (RTOG) 0630, a study of image guided radiation therapy (IGRT) for primary soft tissue sarcomas of the extremity. We analyzed all daily patient-repositioning data collected in this trial to determine the impact of daily IGRT on clinical target volume-to-planning target volume (CTV-to-PTV) margin. METHODS AND MATERIALS: Daily repositioning data, including shifts in right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions and rotations for 98 patients enrolled in RTOG 0630 from 18 institutions were analyzed. Patients were repositioned daily on the basis of bone anatomy by using pretreatment images, including kilovoltage orthogonal images (KVorth), megavoltage orthogonal images (MVorth), KV fan-beam computed tomography (KVCT), KV cone beam CT (KVCB), MV fan-beam CT (MVCT), and MV cone beam CT (MVCB). Means and standard deviations (SDs) for each shift and rotation were calculated for each patient and for each IGRT modality. The Student's t tests and F-tests were performed to analyze the differences in the means and SDs. Necessary CTV-to-PTV margins were estimated. RESULTS: The repositioning shifts and day-to-day variations were large and generally similar for the 6 imaging modalities. Of the 2 most commonly used modalities, MVCT and KVorth, there were no statistically significant differences in the shifts and rotations (P = .15 and .59 for the RL and SI shifts, respectively; and P = .22 for rotation), except for shifts in AP direction (P = .002). The estimated CTV-to-PTV margins in the RL, SI, and AP directions would be 13.0, 10.4, and 11.7 mm from MVCT data, respectively, and 13.1, 8.6, and 10.8 mm from KVorth data, respectively, indicating that margins substantially larger than 5 mm used with daily IGRT would be required in the absence of IGRT. CONCLUSIONS: The observed large daily repositioning errors and the large variations among institutions imply that daily IGRT is necessary for this tumor site, particularly in multi-institutional trials. Otherwise, a CTV-to-PTV margin of 1.5 cm is required to account for daily setup variations. PMID- 26852174 TI - The dosimetric impact of image guided radiation therapy by intratumoral fiducial markers. AB - PURPOSE: Pancreatic fiducials have proven superior over other isocenter localization surrogates, including anatomical landmarks and intratumoral or adjacent stents. The more clinically relevant dosimetric impact of image guided radiation therapy (IGRT) using intratumoral fiducial markers versus bony anatomy has not yet been described and is therefore the focus of the current study. METHODS AND MATERIALS: Using daily orthogonal kV or cone beam computed tomography (CBCT) images and positional and dosimetric data were analyzed for 12 consecutive patients treated with fiducial based IGRT and volumetric modulated arc therapy to the intact pancreas. The shifts from fiducial to bone (DeltaFid-Bone) required to realign the daily fiducial-matched pretreatment images (kV, CBCTs) to the planning computed tomography (CT) using bony anatomic landmarks were recorded. The isocenter was then shifted by (DeltaFid-Bone) for 5 evenly spaced treatments, and the dosimetric impact of DeltaFid-Bone was calculated for planning target volume coverage (PTV50.4 and PTV47.9) and organs at risk (liver, kidney, and stomach/duodenum). RESULTS: The DeltaFid-Bone were greatest in the superoinferior direction (DeltaFid-Bone anteroposterior, 2.7 +/- 3.0; left-right, 2.8 +/- 2.8; superoinferior, 6.3 +/- 7.9 mm; mean +/- standard deviation; P = .03). PTV50.4 coverage was reduced by 13% (fiducial plan 95 +/- 2.0 vs bone plan 82 +/- 12%; P = .005; range, 5%-52%; >5% loss in all; and >10% loss in 42% of patients), and to a lesser degree for PTV47.9 (difference, -8%; range, 1%-30%; fiducial plan 100 +/ 0.3% vs bone plan 92 +/- 7.6%; P = .003; with reductions of >5% in 66% and >10% in 33% of patients). The dosimetric impact of DeltaFid-Bone on the organs at risk was not significant. Positional shifts for kV- and CBCT-based realignments were nearly identical. CONCLUSION: Compared with matching by fiducial markers, IGRT matched by bony anatomy substantially reduces the PTV50.4 and PTV47.9 coverage, supporting the use of intratumoral pancreatic markers for improved targeting in IGRT for pancreatic cancer. PMID- 26852176 TI - Theoretical re-analysis of two previously published datasets. PMID- 26852175 TI - Acquired TERT promoter mutations stimulate TERT transcription in mantle cell lymphoma. AB - Mantle cell lymphoma (MCL) is an aggressive lymphoid neoplasm with poor prognosis. Acquired telomerase reverse transcriptase gene promoter (TERTp) mutations are among the most frequent somatic non-coding mutations in cancers. In this study, the prevalence of TERTp mutations in 24 MCL and 21 other lymphoid neoplasias (oLN) was investigated. Eight MCL samples (33%) carried TERTp mutations, two homozygous and six heterozygous (seven C228T and one C250T), which directly correlated with higher TERT transcription, mitochondrial DNA copy number, and IGHV mutational status in MCL neoplastic cells. TERTp mutations were not found in oLN. TERTp mutations correlated with more lymphoma proliferation and tumor burden, as suggested by the higher number of lymphoma cells circulating in peripheral blood, and tended to associate with longer MCL telomeres, especially in homozygous mutants, although not statistically significant. Telomere-biology genes were overexpressed in MCL cells in comparison to healthy lymphocytes, but were not influenced by mutation status. The findings described for the first time that acquired TERTp mutations are common in MCL but not in other lymphoid neoplasms. It was also demonstrated that TERTp mutations are associated with higher TERT mRNA expression in MCL cells in vivo and higher tumor burden, suggesting these mutations as a driver event in MCL development and progression. PMID- 26852177 TI - Severe Neonatal Hyperbilirubinemia Decreased after the 2007 Canadian Guidelines. AB - OBJECTIVES: To estimate the incidence of severe neonatal hyperbilirubinemia in Canada from 2011-2013 following the implementation of the Canadian Pediatric Society's published guidelines on the management of hyperbilirubinemia in 2007. Our previously reported incidence of hyperbilirubinemia in Canada was 1 in 2480. STUDY DESIGN: Term infants <= 60 days of age, with a peak serum total bilirubin level > 425 MUmol/L or who had an exchange transfusion were followed prospectively through the Canadian Pediatric Surveillance Program from 2011-2013. Infants with rhesus isoimmunization or born < 35 weeks gestation were excluded. RESULTS: Ninety-one cases of severe neonatal hyperbilirubinemia were confirmed. Sixty-nine infants (76%) were readmitted to hospital, 47 (52%) of them within 6 days of age. The remaining 22 infants (24%) were identified with severe neonatal hyperbilirubinemia before they were discharged from the hospital. The mean reported peak bilirubin level was 484 MUmol/L (range 181-788; SD +/- 92). An etiology was identified in 57 (63%) cases, with ABO incompatibility (n = 35) and glucose-6-phosphate dehydrogenase deficiency (n = 11) being the most common. An infant was 3.5 times more likely to be diagnosed with severe neonatal hyperbilirubinemia from 2002-2004 compared with 2011-2013 (95% CI 2.72-4.47). CONCLUSIONS: The minimum estimated incidence of severe neonatal hyperbilirubinemia in Canada is 1 in 8352 live births. Introduction of the Canadian Pediatric Society guidelines and improved physician awareness of severe neonatal hyperbilirubinemia in the last 10 years likely made positive contributions to this trend. PMID- 26852178 TI - Clinical Characteristics of Severe Histiocytic Necrotizing Lymphadenitis (Kikuchi Fujimoto Disease) in Children. AB - OBJECTIVES: To analyze the clinical characteristics of children with Kikuchi Fujimoto disease focusing on cases with prolonged fever. STUDY DESIGN: This was a retrospective study of children diagnosed with Kikuchi-Fujimoto disease from March 2003 to February 2015 in South Korea. Electronic medical records were searched for clinical and laboratory manifestations. RESULTS: Among 86 histopathologically confirmed cases, the mean age was 13.2 (SD +/- 3.1) years, and male to female ratio was 1:1.32. Cervical lymph node enlargement, found in 85 of the patients (99%), was predominantly unilateral in 64 (75%), and involved the cervical lymph node level V in 67 (81%). Fever was present in 76% of the cases, with a median duration of 9 days (IQR 0.25-17.0). Multivariate analysis revealed that a high fever peak >= 39.0 degrees C (P = .010) and presentation with >= 2 systemic symptoms other than fever (P = .027) were factors that were significantly associated with longer fever duration. As the size of the largest lymph node's short diameter increased, the fever duration increased (P = .015). Leukopenia (P = .022) also had a significant association with a longer fever duration. Patients with sonographic findings of conglomerated enlarged lymph nodes had a longer median duration of fever compared with those with separate enlarged lymph nodes (11 vs 4.5 days, P = .019). CONCLUSIONS: Patients with high fever, more systemic symptoms, leukopenia, and larger lymph nodes with a conglomerated distribution may benefit from early recognition and selective consideration of corticosteroid therapy. PMID- 26852179 TI - Progressive Coronary Dilatation Predicts Worse Outcome in Kawasaki Disease. AB - OBJECTIVE: To explore the implication of serial coronary changes on the late coronary outcomes in patients with Kawasaki disease (KD) with coronary aneurysms ? 4 mm. STUDY DESIGN: We performed a retrospective review of 78 patients with KD with large coronary aneurysms (1980-2013, male: 76.9%; 792 patient-years). Progressive coronary dilatation was defined for those with progressive enlargement of coronary arteries in 3 consecutive echocardiograms. RESULTS: We studied 27 patients with KD with giant aneurysms (? 8 mm) and 51 patients with KD with medium aneurysms (4-8 mm). All the giant and 43.1% of medium aneurysms persisted during the study period. For the patients with giant aneurysms, their 10-year freedom from acute myocardial infarction/cardiovascular death and all ischemia was 66% and 52%, respectively. The median intervals for the aneurysm diameters reaching their peak were 3.3 months (giant) and 0.25 months (medium), respectively. In patients with giant aneurysms, the 10-year freedom from ischemia was much lower in those with progressive coronary dilatation (28% vs 59%, P = .021). In patients with medium aneurysms, the probability of 5-year persistence of aneurysm was much greater (67.2% vs 14.8%, P < 10(-3)) in those with progressive coronary dilatation. Male sex and intravenous immunoglobulin therapy were not associated with the late outcomes in the patients with KD who had aneurysms larger than 4 mm. CONCLUSIONS: In addition to coronary diameters 1 month after the onset of KD, progressive coronary dilatation at 2 or more months after diagnosis may be an indicator of duration, and the severity of vasculitis and adverse dilative remodeling were associated with worse late coronary outcomes. PMID- 26852180 TI - Reply. PMID- 26852181 TI - Does the Use of Pacifier Affect Gastro-Esophageal Reflux in Preterm Infants? AB - This crossover study showed that non-nutritive sucking, provided with a pacifier in 30 preterm infants, had no effect on acid and nonacid gastro-esophageal reflux evaluated by esophageal pH-impedance, and thus may be reasonably used in preterm neonates with symptoms of gastro-esophageal reflux. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02023216. PMID- 26852182 TI - Forced expiratory volume in 1 second variability in cystic fibrosis-has the clinical utility been lost in statistical translation? PMID- 26852183 TI - Variations in medial-lateral hamstring force and force ratio influence tibiofemoral kinematics. AB - A change in hamstring strength and activation is typically seen after injuries or invasive surgeries such as anterior cruciate reconstruction or total knee replacement. While many studies have investigated the influence of isometric increases in hamstring load on knee joint kinematics, few have quantified the change in kinematics due to a variation in medial to lateral hamstring force ratio. This study examined the changes in knee joint kinematics on eight cadaveric knees during an open-chain deep knee bend for six different loading configurations: five loaded hamstring configurations that varied the ratio of a total load of 175 N between the semimembranosus and biceps femoris and one with no loads on the hamstring. The anterior-posterior translation of the medial and lateral femoral condyles' lowest points along proximal-distal axis of the tibia, the axial rotation of the tibia, and the quadriceps load were measured at each flexion angle. Unloading the hamstring shifted the medial and lateral lowest points posteriorly and increased tibial internal rotation. The influence of unloading hamstrings on quadriceps load was small in early flexion and increased with knee flexion. The loading configuration with the highest lateral hamstrings force resulted in the most posterior translation of the medial lowest point, most anterior translation of the lateral lowest point, and the highest tibial external rotation of the five loading configurations. As the medial hamstring force ratio increased, the medial lowest point shifted anteriorly, the lateral lowest point shifted posteriorly, and the tibia rotated more internally. The results of this study, demonstrate that variation in medial-lateral hamstrings force and force ratio influence tibiofemoral transverse kinematics and quadriceps loads required to extend the knee. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1707-1715, 2016. PMID- 26852184 TI - Successful rapid subcutaneous desensitization to anakinra in a case of delayed type hypersensitivity reaction. PMID- 26852186 TI - Supporting biodiversity by prescribed burning in grasslands - A multi-taxa approach. AB - There are contrasting opinions on the use of prescribed burning management in European grasslands. On the one hand, prescribed burning can be effectively used for the management of open landscapes, controlling dominant species, reducing accumulated litter or decreasing wildfire risk. On the other hand burning can have a detrimental impact on grassland biodiversity by supporting competitor grasses and by threatening several rare and endangered species, especially arthropods. We studied the effects of prescribed burning in alkaline grasslands of high conservation interest. Our aim was to test whether dormant-season prescribed burning can be an alternative conservation measure in these grasslands. We selected six sites in East-Hungary: in three sites, a prescribed fire was applied in November 2011, while three sites remained unburnt. We studied the effects of burning on soil characteristics, plant biomass and on the composition of vegetation and arthropod assemblages (isopods, spiders, ground beetles and rove beetles). Soil pH, organic matter, potassium and phosphorous did not change, but soluble salt content increased significantly in the burnt sites. Prescribed burning had several positive effects from the nature conservation viewpoint. Shannon diversity and the number of flowering shoots were higher, and the cover of the dominant grass Festuca pseudovina was lower in the burnt sites. Graminoid biomass was lower, while total, green and forb biomass were higher in the burnt plots compared to the control. The key finding of our study was that prescribed burning did not decrease the abundance and diversity of arthropod taxa. Species-level analyses showed that out of the most abundant invertebrate species, 10 were not affected, 1 was negatively and 1 was positively affected by burning. Moreover, our results suggest that prescribed burning leaving unburnt patches can be a viable management tool in open landscapes, because it supports plant diversity and does not threaten arthropods. PMID- 26852185 TI - The role of nutraceuticals for the treatment of non-alcoholic fatty liver disease. AB - Non-alcoholic fatty liver disease (NAFLD) represents the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to liver fibrosis and to cirrhosis. NAFLD is considered as the hepatic component of the metabolic syndrome but mechanisms underlying the onset and progression of NAFLD are still under investigation. The traditional 'two hit hypothesis' has been developed within a more complex 'multiple parallel hit hypothesis' which comprises a wide spectrum of parallel hits. Many therapeutic approaches have been proposed so far and several types of nutraceuticals have been suggested for the treatment of NAFLD and non-alcoholic steatohepatitis (NASH), the most promising of which are those with antioxidant effects. In particular, vitamin E appears to be effective for the treatment of nondiabetic subjects with more advanced NASH, although the high suggested daily dosages are a matter of concern. Moreover, polyphenols reduce liver fat accumulation, mainly by inhibiting lipogenesis. At present, there are insufficient data to support the use of vitamin C supplements in patients with NAFLD. Data on polyunsaturated fatty acid (PUFA) supplementation are heterogeneous, and no well-designed randomized controlled studies (RCTs) of adequate size, with histological assessment of steatosis, have been conducted. Based on the available data, silymarin supplementation for the treatment of NAFLD seems to have a favourable effect. The results with anti-inflammatory agents, such as vitamin D and carnitine are uncertain. In conclusion, there are insufficient data either to support or refute the use of nutraceuticals for subjects with NAFLD. Further RTCs, with histological changes as an outcome measure, are needed. PMID- 26852187 TI - Depression and cholesteatoma: Preliminary findings from a nationwide population based retrospective cohort study. AB - OBJECTIVE: To estimate the risk of developing depressive disorder (DD) following diagnosis with cholesteatoma. METHODS: In the study, we analyzed data from the Longitudinal Health Insurance Database of Taiwan. A total of 599 patients newly diagnosed with cholesteatoma between 1997 and 2007 were included with a comparison cohort of 2995 matched non-cholesteatoma enrollees. Each patient was followed for 3 years to identify the subsequent development of DD. Cox proportional hazard regression analysis was performed to compute adjusted 3-year hazard ratios. RESULTS: The incidence of DD per thousand person-years was approximately twice as high among patients with cholesteatoma (11.32) as among those without cholesteatoma (5.85). After adjusting for potential confounders, patients with cholesteatoma were 1.99 times (95% CI=1.18-3.34, P=0.010) more likely to suffer from DD within 3 years compared to those without cholesteatoma. CONCLUSIONS: This is the first study to demonstrate a link between cholesteatoma and subsequent DD within a three-year followup. We suggest that clinicians keep this critical but neglected issue in mind and carefully investigate the possibility of subsequent psychological problems among cholesteatoma patients. PMID- 26852188 TI - [Effects of physical activity on tobacco craving for smoking cessation]. AB - One in two people who smoke for their whole lifetime will die from a disease related to tobacco use. The smoking habit is sustained by nicotine dependence, which makes smoking cessation very difficult because of withdrawal syndrome and craving (urge to smoke without delay). The aim of this review was to evaluate the impact of physical activity interventions to reduce tobacco craving in smoking cessation. It included 18 randomized controlled trials, which incorporated physical activity. Seventeen of the 18 trials demonstrate the effectiveness of the physical activity in reducing tobacco craving. The consistency of these results constitutes solid evidence of the importance of physical activity as an aid to smoking cessation. Advice to increase physical activity should therefore be given during quit attempts and should be incorporated into smoking cessation programs. PMID- 26852189 TI - Exercise therapy for chronic fatigue syndrome. AB - BACKGROUND: Chronic fatigue syndrome (CFS) is characterised by persistent, medically unexplained fatigue, as well as symptoms such as musculoskeletal pain, sleep disturbance, headaches and impaired concentration and short-term memory. CFS presents as a common, debilitating and serious health problem. Treatment may include physical interventions, such as exercise therapy, which was last reviewed in 2004. OBJECTIVES: The objective of this review was to determine the effects of exercise therapy (ET) for patients with CFS as compared with any other intervention or control.* Exercise therapy versus 'passive control' (e.g. treatment as usual, waiting-list control, relaxation, flexibility).* Exercise therapy versus other active treatment (e.g. cognitive-behavioural therapy (CBT), cognitive treatment, supportive therapy, pacing, pharmacological therapy such as antidepressants).* Exercise therapy in combination with other specified treatment strategies versus other specified treatment strategies (e.g. exercise combined with pharmacological treatment vs pharmacological treatment alone). SEARCH METHODS: We searched The Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR), the Cochrane Central Register of Controlled Trials (CENTRAL) and SPORTDiscus up to May 2014 using a comprehensive list of free-text terms for CFS and exercise. We located unpublished or ongoing trials through the World Health Organization (WHO) International Clinical Trials Registry Platform (to May 2014). We screened reference lists of retrieved articles and contacted experts in the field for additional studies SELECTION CRITERIA: Randomised controlled trials involving adults with a primary diagnosis of CFS who were able to participate in exercise therapy. Studies had to compare exercise therapy with passive control, psychological therapies, adaptive pacing therapy or pharmacological therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection, risk of bias assessments and data extraction. We combined continuous measures of outcomes using mean differences (MDs) and standardised mean differences (SMDs). We combined serious adverse reactions and drop-outs using risk ratios (RRs). We calculated an overall effect size with 95% confidence intervals (CIs) for each outcome. MAIN RESULTS: We have included eight randomised controlled studies and have reported data from 1518 participants in this review. Three studies diagnosed individuals with CFS using the 1994 criteria of the Centers for Disease Control and Prevention (CDC); five used the Oxford criteria. Exercise therapy lasted from 12 to 26 weeks. Seven studies used variations of aerobic exercise therapy such as walking, swimming, cycling or dancing provided at mixed levels in terms of intensity of the aerobic exercise from very low to quite rigorous, whilst one study used anaerobic exercise. Control groups consisted of passive control (eight studies; e.g. treatment as usual, relaxation, flexibility) or CBT (two studies), cognitive therapy (one study), supportive listening (one study), pacing (one study), pharmacological treatment (one study) and combination treatment (one study). Risk of bias varied across studies, but within each study, little variation was found in the risk of bias across our primary and secondary outcome measures.Investigators compared exercise therapy with 'passive' control in eight trials, which enrolled 971 participants. Seven studies consistently showed a reduction in fatigue following exercise therapy at end of treatment, even though the fatigue scales used different scoring systems: an 11-item scale with a scoring system of 0 to 11 points (MD -6.06, 95% CI -6.95 to -5.17; one study, 148 participants; low-quality evidence); the same 11-item scale with a scoring system of 0 to 33 points (MD -2.82, 95% CI -4.07 to -1.57; three studies, 540 participants; moderate-quality evidence); and a 14-item scale with a scoring system of 0 to 42 points (MD -6.80, 95% CI -10.31 to -3.28; three studies, 152 participants; moderate-quality evidence). Serious adverse reactions were rare in both groups (RR 0.99, 95% CI 0.14 to 6.97; one study, 319 participants; moderate quality evidence), but sparse data made it impossible for review authors to draw conclusions. Study authors reported a positive effect of exercise therapy at end of treatment with respect to sleep (MD -1.49, 95% CI -2.95 to -0.02; two studies, 323 participants), physical functioning (MD 13.10, 95% CI 1.98 to 24.22; five studies, 725 participants) and self-perceived changes in overall health (RR 1.83, 95% CI 1.39 to 2.40; four studies, 489 participants). It was not possible for review authors to draw conclusions regarding the remaining outcomes.Investigators compared exercise therapy with CBT in two trials (351 participants). One trial (298 participants) reported little or no difference in fatigue at end of treatment between the two groups using an 11-item scale with a scoring system of 0 to 33 points (MD 0.20, 95% CI -1.49 to 1.89). Both studies measured differences in fatigue at follow-up, but neither found differences between the two groups using an 11-item fatigue scale with a scoring system of 0 to 33 points (MD 0.30, 95% CI -1.45 to 2.05) and a nine-item Fatigue Severity Scale with a scoring system of 1 to 7 points (MD 0.40, 95% CI -0.34 to 1.14). Serious adverse reactions were rare in both groups (RR 0.67, 95% CI 0.11 to 3.96). We observed little or no difference in physical functioning, depression, anxiety and sleep, and we were not able to draw any conclusions with regard to pain, self-perceived changes in overall health, use of health service resources and drop-out rate.With regard to other comparisons, one study (320 participants) suggested a general benefit of exercise over adaptive pacing, and another study (183 participants) a benefit of exercise over supportive listening. The available evidence was too sparse to draw conclusions about the effect of pharmaceutical interventions. AUTHORS' CONCLUSIONS: Patients with CFS may generally benefit and feel less fatigued following exercise therapy, and no evidence suggests that exercise therapy may worsen outcomes. A positive effect with respect to sleep, physical function and self-perceived general health has been observed, but no conclusions for the outcomes of pain, quality of life, anxiety, depression, drop-out rate and health service resources were possible. The effectiveness of exercise therapy seems greater than that of pacing but similar to that of CBT. Randomised trials with low risk of bias are needed to investigate the type, duration and intensity of the most beneficial exercise intervention. PMID- 26852190 TI - Nondermatophytic onychomycosis by Fusarium oxysporum in an immunocompetent host. AB - Fusarium onychomycosis is not uncommon in tropical countries but is worth reporting. We report a case of nondermatophytic onychomycosis by Fusarium oxysporum in an immunocompetent woman from Buldhana district of Maharashtra (India). Bilateral involvement of great toe nail, chronic duration and acquisition of infection due to peculiar practice of daily pasting floors with mud and dung, is interesting. The case was successfully treated with topical and oral terbinafine with a dose of 250 mg daily for 3 weeks. PMID- 26852191 TI - In vitro antifungal susceptibility of clinical species belonging to Aspergillus genus and Rhizopus oryzae. AB - OBJECTIVE: Among filamentous fungal pathogens, Aspergillus spp. and zygomycetes account for highest rates of morbidity and mortality among immunocompromised patients. Recently developed antifungal drugs offer the potential to improve management and therapeutic outcomes of fungal infections. The aim of this study was to analyse the in vitro activities of voriconazole, itraconazole, amphotericin B and caspofungin against clinical isolates of Aspergillus spp. and Rhizopus oryzae. MATERIAL AND METHODS: The in vitro antifungal susceptibility of 54 isolates belonging to different clinical isolates of Aspergillus spp. and R. oryzae was tested for four antifungal agents using a microdilution reference method (CLSI, M38-A2). All isolates were identified by typical colony and microscopic characteristics, and also characterized by molecular methods. RESULTS: Caspofungin (MEC range: 0.008-0.25 and MEC50: 0.0023MUg/mL) was the most active drug in vitro against Aspergillus spp., followed by voriconazole (MIC range: 0.031-8 and MIC50: 0.5MUg/mL), itraconazole (MIC range: 0.031-16 and MIC50: 0.25MUg/mL), and amphotericin B (MIC range: 0.125-4 and MIC50: 0.5MUg/mL), in order of decreasing activity. The caspofungin, voriconazole, and itraconazole demonstrated poor in vitro activity against R. oryzae isolates evaluated, followed by amphotericin B. CONCLUSION: This study demonstrates that caspofungin had good antifungal activity and azole agents had better activity than amphotericin B against Aspergillus species. Although, azole drugs are considered ineffective against R. oryzae. This result is just from a small scale in vitro susceptibility study and we did not take other factors into consideration. PMID- 26852192 TI - Pathogenicity of Candida albicans isolates from bloodstream and mucosal candidiasis assessed in mice and Galleria mellonella. AB - The working hypothesis of this study was to elucidate a possible association between the pathogenic potential of Candida albicans strains with a clinical entity, systemic versus superficial candidiasis. Specifically, we assessed the pathogenicity of two groups of clinical C. albicans isolates: isolates from bloodstream infection (S) versus isolates from vaginitis patients (M), in two experimental in vivo systems - mice and Galleria melonella, in comparison to a control strain (CBS 562). Mice and G. mellonella larvae were inoculated with CBS 562 and the different S and M isolates, and followed up for survival rate and survival time during 30 and 7 days, respectively. Candida kidney colonization of mice was assessed by histopathology and colony-forming units' enumeration. The results revealed: (1) S and M isolates had different behavior patterns in the two models and varied in different parameters; (2) no statistically significant difference in pathogenicity between S and M isolates as whole groups was noted; (3) S14 was the most virulent isolate and close to the standard strain CBS 562 in both models. This study is distinctive in its outline combining two different groups of C. albicans clinical isolates originating from two different clinical entities that were assessed in vivo concurrently in two models. PMID- 26852193 TI - Successful treatment of severe kerion Celsi in an immunocompromised girl with evacuation of pus, terbinafine and short course glucocorticosteroids. AB - A 6-year-old girl with a 2-year history of idiopathic thrombocytopenic purpura complained of a 4-week history of scalp desquamation together with small pustules. During the recent 10 days, she complained of high fever with multiple abscesses formation with no response to intravenous antibiotics. She received varied doses of oral prednisone therapy for 2 years. Microscopy showed endothrix infection. We prescribed terbinafine 125 mg/d and prednisone 10 mg/d. After 1 week, she returned to our office with severe ache and persistent high fever. She refused any topical drugs because of pain. Manual pressure to remove pus from sinuses and infected scale under general anesthesia was done and about 100 ml pus was discharged from kerion lesions. Prednisone (1 mg/kg/d) was started and fever disappeared on the same day. Prednisone was tapered to withdraw in 10 days. A total of a 3-month course of oral terbinafine (125 mg/d) resulted in mycological clearance. Hair regrowth was satisfactory 8 months later. PMID- 26852194 TI - Aspergillus tubingensis and Aspergillus niger as the dominant black Aspergillus, use of simple PCR-RFLP for preliminary differentiation. AB - This work aimed to identify the species distribution of common clinical and environmental isolates of black Aspergilli based on simple restriction fragment length polymorphism (RFLP) analysis of the beta-tubulin gene. A total of 149 clinical and environmental strains of black Aspergilli were collected and subjected to preliminary morphological examination. Total genomic DNAs were extracted, and PCR was performed to amplify part of the beta-tubulin gene. At first, 52 randomly selected samples were species-delineated by sequence analysis. In order to distinguish the most common species, PCR amplicons of 117 black Aspergillus strains were identified by simple PCR-RFLP analysis using the enzyme TasI. Among 52 sequenced isolates, 28 were Aspergillus tubingensis, 21 Aspergillus niger, and the three remaining isolates included Aspergillus uvarum, Aspergillus awamori, and Aspergillus acidus. All 100 environmental and 17 BAL samples subjected to TasI-RFLP analysis of the beta-tubulin gene, fell into two groups, consisting of about 59% (n=69) A. tubingensis and 41% (n=48) A. niger. Therefore, the method successfully and rapidly distinguished A. tubingensis and A. niger as the most common species among the clinical and environmental isolates. Although tardy, the Ehrlich test was also able to differentiate A. tubingensis and A. niger according to the yellow color reaction specific to A. niger. A. tubingensis and A. niger are the most common black Aspergillus in both clinical and environmental isolates in Iran. PCR-RFLP using TasI digestion of beta-tubulin DNA enables rapid screening for these common species. PMID- 26852196 TI - A differentially selective probe based on diketopyrrolopyrrole with fluorescence turn-on response to Fe(3+), and dual-mode turn-on and ratiometric response to Au(3+), and its application in living cell imaging. AB - A diketopyrrolopyrrole-based probe DPP-PyR was able to recognize Fe(3+) and Au(3+) with fluorescent turn-on response via different emission modes with relatively low detection limit. Moreover, DPP-PyR exhibited preferential second mode of selectivity for Au(3+) as it ratiometrically displaced Fe(3+) from the [DPP-PyR+Fe(3+)] complex. Furthermore, the imaging experiments indicated that this probe was cell-permeable and could be used to detect Fe(3+) and Au(3+) ions within living cell. To the best of our knowledge, it was the first probe for detection Fe(3+) and Au (3+) at the same time ever reported. PMID- 26852197 TI - Realization of a label-free electrochemical immunosensor for detection of low density lipoprotein using NiO thin film. AB - A label-free electrochemical immunosensor, based on nickel oxide (NiO) thin film, for the detection of low density lipoprotein (LDL) has been proposed. P-type semiconducting NiO thin film was deposited by RF sputtering technique and its properties were investigated by X-ray diffraction and Fourier transform infrared spectroscopy. The NiO thin film was utilized as an efficient matrix for the covalent immobilization of apolipoprotein B-100 antibody using EDC/NHS chemistry. The immunoelectrode, thus prepared, was studied using differential pulse voltammetry, cyclic voltammetry and electrochemical impedance spectroscopy. The impedimetric response of the immunosensor exhibited a high sensitivity of 12 kOmega MUM(-1) over a wide linear range (0.018-0.5 MUM) of LDL. The long shelf life (18 weeks) and enhanced performance characteristics of the immunosensor demonstrate the excellent ability of the NiO matrix for quantification of LDL at commercial level. PMID- 26852198 TI - Bead-based microarray immunoassay for lung cancer biomarkers using quantum dots as labels. AB - In this study, we developed a multiplex immunoassay system that combines the suspension and planar microarray formats within a single layer of polydimethylsiloxane (PDMS) using soft lithography technology. The suspension format was based on the target proteins forming a sandwich structure between the magnetic beads and the quantum dot (QD) probes through specific antibody-antigen interactions. The planar microarray format was produced by fabricating an array of micro-wells in PDMS. Each micro-well was designed to trap a single microbead and eventually generated a microbead array within the PDMS chamber. The resultant bead-based on-chip assay could be used for simultaneously detecting three lung cancer biomarkers-carcinoembryonic antigen (CEA), fragments of cytokeratin 19 (CYFRA21-1) and neuron-specific enolase (NSE)-in 10 MUl of human serum, with a wide linear dynamic range (1.03-111 ng/mL for CEA and CYFRA21-1; 9.26-1000 ng/ml for NSE) and a low detection limit (CEA: 0.19 ng/ml; CYFRA21-1: 0.97 ng/ml; NSE: 0.37 ng/ml; S/N=3). Our micro-well chip does not require complex e-beam lithography or the reactive ion etching process as with existing micro-well systems, which rely on expensive focused ion beam (FIB) milling or optical fiber bundles. Furthermore, the current approach is easy to operate without extra driving equipment such as pumps, and can make parallel detection for multiplexing with rapid binding kinetics, small reagent consumption and low cost. This work has demonstrated the importance of the successful application of on-chip multiplexing sandwich assays for the detection of biomarker proteins. PMID- 26852195 TI - Subjective memory decline predicts greater rates of clinical progression in preclinical Alzheimer's disease. AB - INTRODUCTION: The objective of this study was to determine the utility of subjective memory decline (SMD) to predict episodic memory change and rates of clinical progression in cognitively normal older adults with evidence of high beta-amyloid burden (CN Abeta+). METHODS: Fifty-eight CN Abeta+ participants from the Australian Imaging, Biomarkers, and Lifestyle study responded to an SMD questionnaire and underwent comprehensive neuropsychological assessments. Participant data for three follow-up assessments were analyzed. RESULTS: In CN Abeta+, subjects with high SMD did not exhibit significantly greater episodic memory decline than those with low SMD. High SMD was related to greater rates of progression to mild cognitive impairment or Alzheimer's disease (AD) dementia (hazard ratio = 5.1; 95% confidence interval, 1.4-20.0, P = .02) compared with low SMD. High SMD was associated with greater depressive symptomatology and smaller left hippocampal volume. DISCUSSION: High SMD is a harbinger of greater rates of clinical progression in preclinical AD. Although SMD reflects broader diagnostic implications for CN Abeta+, more sensitive measures may be required to detect early subtle cognitive change. PMID- 26852199 TI - Silver nanoflower-reduced graphene oxide composite based micro-disk electrode for insulin detection in serum. AB - Sensitive and selective determination of protein biomarkers remains a significant challenge due to the existence of various biomarkers in human body at a low concentration level. Therefore, new technologies were incessantly steered to detect tiny biomarkers at a low concentration level, yet, it is difficult to develop reliable, stable and sensitive detection methods for disease diagnostics. Therefore, the present study demonstrates a methodology to detect insulin in serum at low levels based on Ag nanoflower (AgNF) decorated reduced graphene oxide (rGO) modified micro-disk electrode arrays (MDEAs). The morphology of AgNF rGO composite was characterized by scanning electron microscopy, the structure was analyzed using X-ray diffraction patterns and Raman spectra. The hybrid interface exhibited enhanced electrical conductivity when compared with its individual elements and had improved capturing ability for antibody-antigen binding towards insulin detection. In order to measure quantitatively the insulin concentration in PBS and human serum, the change in impedance (DeltaZ) from electrochemical impedance spectroscopy was analyzed for various concentrations of insulin in [Fe(CN)6](3-/4-) redox couple. The electrode with adsorbed antibodies showed an increase in DeltaZ for the addition of antigen concentrations over a working range of 1-1000 ng mL(-1). The detection limits were 50 and 70 pg mL(-1) in PBS and human serum, respectively. PMID- 26852200 TI - Functional surface engineering of quantum dot hydrogels for selective fluorescence imaging of extracellular lactate release. AB - Selective and sensitive detection of extracellular lactate is of fundamental significance for studying the metabolic alterations in tumor progression. Here we report the rational design and synthesis of a quantum-dot-hydrogel-based fluorescent probe for biosensing and bioimaging the extracellular lactate. By surface engineering the destabilized quantum dot sol with Nile Blue, the destabilized Nile-Blue-functionalized quantum dot sol cannot only self-assemble forming quantum dot hydrogel but also monitor lactate in the presence of nicotinamide adenine dinucleotide cofactor and lactate dehydrogenase through fluorescence resonance energy transfer. Notably, the surface engineered quantum dot hydrogel show high selectivity toward lactate over common metal ions, amino acids and other small molecules that widely coexist in biological system. Moreover, the destabilized Nile-Blue-functionalized quantum dots can encapsulate isolated cancer cells when self-assembled into a hydrogel and thus specifically detect and image the extracellular lactate metabolism. By virtue of these properties, the functionalized quantum dot hydrogel was further successfully applied to monitor the effect of metabolic agents. PMID- 26852201 TI - Probing minority population of antibiotic-resistant bacteria. AB - The evolution and spread of antibiotic-resistant pathogens has become a major threat to public health. Advanced tools are urgently needed to quickly diagnose antibiotic-resistant infections to initiate appropriate treatment. Here we report the development of a highly sensitive flow cytometric method to probe minority population of antibiotic-resistant bacteria via single cell detection. Monoclonal antibody against TEM-1 beta-lactamase and Alexa Fluor 488-conjugated secondary antibody were used to selectively label resistant bacteria green, and nucleic acid dye SYTO 62 was used to stain all the bacteria red. A laboratory-built high sensitivity flow cytometer (HSFCM) was applied to simultaneously detect the side scatter and dual-color fluorescence signals of single bacteria. By using E. coli JM109/pUC19 and E. coli JM109 as the model systems for antibiotic-resistant and antibiotic-susceptible bacteria, respectively, as low as 0.1% of antibiotic resistant bacteria were accurately quantified. By monitoring the dynamic population change of a bacterial culture with the administration of antibiotics, we confirmed that under the antimicrobial pressure, the original low population of antibiotic-resistant bacteria outcompeted susceptible strains and became the dominant population after 5hours of growth. Detection of antibiotic-resistant infection in clinical urine samples was achieved without cultivation, and the bacterial load of susceptible and resistant strains can be faithfully quantified. Overall, the HSFCM-based quantitative method provides a powerful tool for the fundamental studies of antibiotic resistance and holds the potential to provide rapid and precise guidance in clinical therapies. PMID- 26852202 TI - First paraben substituted cyclotetraphosphazene compounds and DNA interaction analysis with a new automated biosensor. AB - Cancer, as one of the leading causes of death in the world, is caused by malignant cell division and growth that depends on rapid DNA replication. To develop anti-cancer drugs this feature of cancer could be exploited by utilizing DNA-damaging molecules. To achieve this, the paraben substituted cyclotetraphosphazene compounds have been synthesized for the first time and their effect on DNA (genotoxicity) has been investigated. The conventional genotoxicity testing methods are laborious, take time and are expensive. Biosensor based assays provide an alternative to investigate this drug/compound DNA interactions. Here for the first time, a new, easy and rapid screening method has been used to investigate the DNA damage, which is based on an automated biosensor device that relies on the real-time electrochemical profiling (REPTM) technology. Using both the biosensor based screening method and the in vitro biological assay, the compounds 9 and 11 (propyl and benzyl substituted cyclotetraphosphazene compounds, respectively), have resulted in higher DNA damage than the others with 65% and 80% activity reduction, respectively. PMID- 26852203 TI - Ultrasensitive electrochemical sensor for Hg(2+) by using hybridization chain reaction coupled with Ag@Au core-shell nanoparticles. AB - A novel electrochemical biosensor for Hg(2+) detection was reported by using DNA based hybridization chain reaction (HCR) coupled with positively charged Ag@Au core-shell nanoparticles ((+)Ag@Au CSNPs) amplification. To construct the sensor, capture probe (CP ) was firstly immobilized onto the surface of glass carbon electrode (GCE). In the presence of Hg(2+), the sandwiched complex can be formed between the immobilized CP on the electrode surface and the detection probe (DP) modified on the gold nanoparticles (AuNPs) based on T-Hg(2+)-T coordination chemistry. The carried DP then opened two ferrocene (Fc) modified hairpin DNA (H1 and H2) in sequence and propagated the happen of HCR to form a nicked double helix. Numerous Fc molecules were formed on the neighboring probe and produced an obvious electrochemical signal. Moreover, (+)Ag@Au CSNPs were assembly onto such dsDNA polymers as electrochemical signal enhancer. Under optimal conditions, such sensor presents good electrochemical responses for Hg(2+) detection with a detection limit of 3.6 pM. Importantly, the methodology has high selectivity for Hg(2+) detection. PMID- 26852204 TI - Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions. AB - Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR 8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy. PMID- 26852206 TI - Enrofloxacin at environmentally relevant concentrations enhances uptake and toxicity of cadmium in the earthworm Eisenia fetida in farm soils. AB - Individual and combined effects of enrofloxacin (EF) and cadmium (Cd) on the earthworm Eisenia fetida at environmentally relevant concentrations were investigated. EF is a veterinary antibiotic; Cd is an impurity in phosphatic fertiliser. For both, residues may accumulate in farm soils. In laboratory tests, over 98% of spiked EF was adsorbed by farm soils, with a half-life >8 weeks. However, earthworms absorbed less than 20% of spiked EF. Earthworms in soil with EF concentration 10 mg kg(-1) soil experienced transient oxidative stress and exhibited reduced burrowing activity and respiration after an 8-week exposure; EF at 0.1 and 1.0 mg kg(-1) soil did not elicit toxicity symptoms. When both were added, Cd did not affect EF uptake, but each increment of spiked EF increased Cd bioaccumulation and associated oxidative stress of earthworms, and also caused decreased burrow length and CO2 production. However, metallothionein induction was not affected. The enhanced toxicity of Cd to earthworms in the presence of EF at low environmental concentrations may have implications for the health and reproductive success of earthworm populations and highlights the importance of understanding effects of antibiotic contamination of farm soils, and of awareness of environmental effects from interaction between multiple contaminants. PMID- 26852205 TI - Effect of NaX zeolite-modified graphite felts on hexavalent chromium removal in biocathode microbial fuel cells. AB - Two kinds of NaX zeolite-modified graphite felts were used as biocathode electrodes in hexavalent chromium (Cr(VI))-reducing microbial fuel cells (MFCs). The one was fabricated through direct modification, and the other one processed by HNO3 pretreatment of graphite felt before modification. The results showed that two NaX zeolite-modified graphite felts are excellent bio-electrode materials for MFCs, and that a large NaX loading mass, obtained by HNO3 pretreatment (the HNO3-NaX electrode), leads to a superior performance. The HNO3 NaX electrode significantly improved the electricity generation and Cr(VI) removal of the MFC. The maximum Cr(VI) removal rate increased to 10.39+/-0.28 mg/L h, which was 8.2 times higher than that of the unmodified control. The improvement was ascribed to the strong affinity that NaX zeolite particles, present in large number on the graphite felt, have for microorganisms and Cr(VI) ions. PMID- 26852207 TI - Assessment of asbestos exposure during a simulated agricultural activity in the proximity of the former asbestos mine of Balangero, Italy. AB - The natural occurrence of asbestos (NOA) in rural areas is a serious concern for human health and the dispersion route of asbestos in the proximity of natural asbestos-rich settings has been marginally evaluated so far. NOA may affect air, but also water and soil quality. In rural areas population may be exposed to asbestos with a largely unknown impact on human health. This work investigates the potential exposure of a farmer cultivating a field nearby the largest former asbestos mine of Western Europe (Balangero, Italy). The concentration of waterborne asbestos in the stream used to water the field was measured (ca. 2*10(5) fibers per liter, ff/L) and the cultivated ultramafic topsoil characterized, evidencing a remarkable occurrence of chrysotile. The worker's personal exposure and the environmental fiber dispersion during a simulated agricultural activity (tillage) were quantified in two independent trials. During the trials, the worker was exposed to average concentrations of 16 and 26 ff/L, with a peak of 40 ff/L. These data inform about the possible exposure of an agricultural worker to asbestos concentration higher than the accepted threshold of 2 ff/L. The release of asbestos fibers into the environment was negligible (0 2 ff/L). PMID- 26852208 TI - Where does the toxicity of metal oxide nanoparticles come from: The nanoparticles, the ions, or a combination of both? AB - The toxicity of metal oxide nanoparticles (NPs) has aroused great concern over the past few years. However, there still remains the question whether the toxicity of the metal oxide NPs originates from the released ions or the NPs themselves. In this study, the metal ion release of CuO, Fe2O3, ZnO, Co3O4, Cr2O3, and NiO NPs in aqueous media was investigated, and their contributions to the metal oxide NPs' inhibition on the bioluminescence of Photobacterium phosphoreum were studied. It was found that the ions release of the metal oxide NPs in aqueous media was complex, depending on both the dissolution and adsorption processes of the metal oxide NPs. The relationships between the metal oxide NPs' antibacterial effects and their released metal ions could be divided into three categories: (1) the ZnO NPs' antibacterial effect was due solely to the released Zn(2+); (2) the CuO NPs' antibacterial effect originated from both the released Cu(2+),and the CuO particles; and (3) the antibacterial effects of Fe2O3, Co3O4, Cr2O3, and NiO NPs were caused by the NPs themselves. Our findings suggest that the ions release and their contributions to the NPs' toxicity should be considered in the toxicity evaluations of the metal oxide NPs. PMID- 26852209 TI - Aerobic degradation of BDE-209 by Enterococcus casseliflavus: Isolation, identification and cell changes during degradation process. AB - Decabromodiphenyl ether (BDE-209) is one of the most commonly used brominated flame retardants that have contaminated the environment worldwide. Microbial bioremediation has been considered as an effective technique to remove these sorts of persistent organic pollutants. Enterococcus casseliflavus, a gram positive bacterium capable of aerobically transforming BDE-209, was isolated by our team from sediments in Guiyu, an e-waste dismantling area in Guangdong Province, China. To promote microbial bioremediation of BDE-209 and elucidate the mechanism behind its aerobic degradation, the effects of BDE-209 on the cell changes of E. casseliflavus were examined in this study. The experimental results demonstrated that the high cell surface hydrophobicity (CSH) of E. casseliflavus made the bacteria absorb hydrophobic BDE-209 more easily. E. casseliflavus responded to BDE-209 stress, resulting in an increase in cell membrane permeability and accumulation of BDE-209 inside the cell. The differential expression of intracellular protein was analyzed through two-dimensional gel electrophoresis (2-DE). More than 50 differentially expressed protein spots were reproducibly detected, including 25 up, and 25 down regulated after a 4 days exposure. Moreover, the apoptotic-like cell changes were observed during E. casseliflavus mediated degradation of BDE-209 by means of flow cytometry. PMID- 26852210 TI - Chemical and structural characterization of copper adsorbed on mosses (Bryophyta). AB - The adsorption of copper on passive biomonitors (devitalized mosses Hypnum sp., Sphagnum denticulatum, Pseudoscleropodium purum and Brachythecium rutabulum) was studied under different experimental conditions such as a function of pH and Cu concentration in solution. Cu assimilation by living Physcomitrella patents was also investigated. Molecular structure of surface adsorbed and incorporated Cu was studied by X-ray Absorption Spectroscopy (XAS). Devitalized mosses exhibited the universal adsorption pattern of Cu as a function of pH, with a total binding sites number 0.05-0.06 mmolg(dry)(-1) and a maximal adsorption capacity of 0.93 1.25 mmolg(dry)(-1) for these devitalized species. The Extended X-ray Absorption Fine Structure (EXAFS) fit of the first neighbor demonstrated that for all studied mosses there are ~4.5 O/N atoms around Cu at ~1.95 A likely in a pseudo square geometry. The X-ray Absorption Near Edge Structure (XANES) analysis demonstrated that Cu(II)-cellulose (representing carboxylate groups) and Cu(II) phosphate are the main moss surface binding moieties, and the percentage of these sites varies as a function of solution pH. P. patens exposed during one month to Cu(2+) yielded ~20% of Cu(I) in the form of Cu-S(CN) complexes, suggesting metabolically-controlled reduction of adsorbed and assimilated Cu(2+). PMID- 26852211 TI - Uptake, translocation and possible biodegradation of the antidiabetic agent metformin by hydroponically grown Typha latifolia. AB - The increasing load of pharmaceutical compounds has raised concerns about their potential residues in aquatic environments and ecotoxicity. Metformin (MET), a widely prescribed antidiabetic II medicine, has been detected in high concentration in sewage and in wastewater treatment effluents. An uptake and translocation study was carried out to assess the ultimate fate of MET in phytoremediation. MET was removed from media by Typha latifolia, and the removal processes followed first order kinetics. After 28 days, the removal efficiencies were in a range of 74.0+/-4.1-81.1+/-3.3%. In roots, MET concentration was increasing during the first two weeks of the experiment but thereafter decreasing. In contrast, MET concentration was continuously increasing in rhizomes and leaves. Bioaccumulation of MET in roots was much higher than in leaves and rhizomes. As degradation product of metformin in the plant, methylbiguanide (MBG) was detected whereas guanylurea was undetectable. Moreover, MBG concentration in roots was increasing with exposure time. An enzymatic degradation experiment showed the degradation rate followed the order of MET= 50 % was calculated for CTP and CTA with diffusion weighted imaging and digital subtraction angiography as reference standards. Effective radiation dose was compared. RESULTS: There were no differences in any perfusion parameter value between three groups (P > 0.05). No difference was found in subjective image quality between three groups (P > 0.05). Diagnostic accuracy for detecting acute infarct and vascular stenosis showed no difference between three groups (P > 0.05). Compared with group A, radiation doses of groups B and C were decreased by 28 % and 37 % (both P < 0.001), respectively. CONCLUSION: Compared with 80 kVp protocol, 70 kVp brain CTP allows comparable vascular and perfusion assessment and lower radiation dose while maintaining high diagnostic accuracy in detecting acute infarct. KEY POINTS: * 70 kVp whole brain CTP can provide diagnostic image quality. * 70 kVp CTP diagnostic accuracy was maintained vs. 80 kVp protocol. * 70 kVp CTP radiation doses were lower than 80 kVp protocol. PMID- 26852215 TI - CT-based compartmental quantification of adipose tissue versus body metrics in colorectal cancer patients. AB - PURPOSE: While obesity is considered a prognostic factor in colorectal cancer (CRC), there is increasing evidence that not simply body mass index (BMI) alone but specifically abdominal fat distribution is what matters. As part of the ColoCare study, this study measured the distribution of adipose tissue compartments in CRC patients and aimed to identify the body metric that best correlates with these measurements as a useful proxy for adipose tissue distribution. MATERIALS AND METHODS: In 120 newly-diagnosed CRC patients who underwent multidetector computed tomography (CT), densitometric quantification of total (TFA), visceral (VFA), intraperitoneal (IFA), retroperitoneal (RFA), and subcutaneous fat area (SFA), as well as the M. erector spinae and psoas was performed to test the association with gender, age, tumor stage, metabolic equivalents, BMI, waist-to-height (WHtR) and waist-to-hip ratio (WHR). RESULTS: VFA was 28.8 % higher in men (pVFA<0.0001) and 30.5 % higher in patients older than 61 years (pVFA<0.0001). WHtR correlated best with all adipose tissue compartments (rVFA=0.69, rTFA=0.84, p<0.0001) and visceral-to-subcutaneous-fat ratio (VFR, rVFR=0.22, p=<0.05). Patients with tumor stages III/IV showed significantly lower overall adipose tissue than I/II. Increased M. erector spinae mass was inversely correlated with all compartments. CONCLUSION: Densitometric quantification on CT is a highly reproducible and reliable method to show fat distribution across adipose tissue compartments. This distribution might be best reflected by WHtR, rather than by BMI or WHR. KEY POINTS: * Densitometric quantification of adipose tissue on CT is highly reproducible and reliable. * Waist-to-height ratio better correlates with adipose tissue compartments and VFR than BMI or waist-to-hip ratio. * Men have higher a higher visceral fat area than women. * Patients older than 61 years have higher visceral fat area. * Patients with tumor stages III/IV have significantly lower adipose tissue than those in stages I/II. PMID- 26852217 TI - The predictive value of preoperative 18F-fluorodeoxyglucose PET for postoperative recurrence in patients with localized primary gastrointestinal stromal tumour. AB - OBJECTIVES: To assess the potential value of preoperative 18F-FDG PET to predict postoperative recurrence of solitary localized primary gastrointestinal stromal tumour (GIST) after radical resection. METHODS: A total of 46 patients with primary GIST who received preoperative 18F-FDG PET and underwent complete resection without neoadjuvant therapy were retrospectively studied. PET findings, including ring-shaped uptake and intense uptake, were compared with Joensuu risk grades using Fisher's exact test. The prognostic value of the preoperative clinico-imaging variables-age >=60 years, male, ring-shaped uptake, intense uptake, tumour size >5 cm, heterogeneous CT attenuation and lower gastrointestinal origin-and Joensuu high risk for recurrence-free survival was evaluated using log-rank test and multivariate Cox regression analysis. RESULTS: Ring-shaped uptake and intense uptake were significantly associated with Joensuu high risk. Univariate analysis showed that ring-shaped uptake, intense uptake, size >5 cm and Joensuu high risk were significantly associated with inferior recurrence-free survival. Multivariate analysis showed that ring-shaped uptake (P = 0.004) and Joensuu high risk (P = 0.021) were independent adverse prognostic factors of postoperative recurrence. CONCLUSIONS: Ring-shaped uptake on preoperative 18F-FDG PET may be a potential predictor of postoperative tumour recurrence of localized primary GISTs. KEY POINTS: * Clinical course of resectable solitary localized primary GISTs varies widely. * Ring-shaped uptake is an independent adverse prognostic factor of postoperative recurrence. * Preoperative 18 F-FDG PET may help predict postoperative recurrence of GISTs. PMID- 26852218 TI - Optimising MR perfusion imaging: comparison of different software-based approaches in acute ischaemic stroke. AB - OBJECTIVES: Perfusion imaging (PI) is susceptible to confounding factors such as motion artefacts as well as delay and dispersion (D/D). We evaluate the influence of different post-processing algorithms on hypoperfusion assessment in PI analysis software packages to improve the clinical accuracy of stroke PI. METHODS: Fifty patients with acute ischaemic stroke underwent MRI imaging in the first 24 h after onset. Diverging approaches to motion and D/D correction were applied. The calculated MTT and CBF perfusion maps were assessed by volumetry of lesions and tested for agreement with a standard approach and with the final lesion volume (FLV) on day 6 in patients with persisting vessel occlusion. RESULTS: MTT map lesion volumes were significantly smaller throughout the software packages with correction of motion and D/D when compared to the commonly used approach with no correction (p = 0.001-0.022). Volumes on CBF maps did not differ significantly (p = 0.207-0.925). All packages with advanced post processing algorithms showed a high level of agreement with FLV (ICC = 0.704 0.879). CONCLUSIONS: Correction of D/D had a significant influence on estimated lesion volumes and leads to significantly smaller lesion volumes on MTT maps. This may improve patient selection. KEY POINTS: * Assessment on hypoperfusion using advanced post-processing with correction for motion and D/D. * CBF appears to be more robust regarding differences in post-processing. * Tissue at risk is estimated more accurately by correcting software algorithms. * Advanced post processing algorithms show a higher agreement with the final lesion volume. PMID- 26852219 TI - First clinical experience with a dedicated MRI-guided high-intensity focused ultrasound system for breast cancer ablation. AB - OBJECTIVES: To assess the safety and feasibility of MRI-guided high-intensity focused ultrasound (MR-HIFU) ablation in breast cancer patients using a dedicated breast platform. METHODS: Patients with early-stage invasive breast cancer underwent partial tumour ablation prior to surgical resection. MR-HIFU ablation was performed using proton resonance frequency shift MR thermometry and an MR HIFU system specifically designed for breast tumour ablation. The presence and extent of tumour necrosis was assessed by histopathological analysis of the surgical specimen. Pearson correlation coefficients were calculated to assess the relationship between sonication parameters, temperature increase and size of tumour necrosis at histopathology. RESULTS: Ten female patients underwent MR-HIFU treatment. No skin redness or burns were observed in any of the patients. No correlation was found between the applied energy and the temperature increase. In six patients, tumour necrosis was observed with a maximum diameter of 3-11 mm. In these patients, the number of targeted locations was equal to the number of areas with tumour necrosis. A good correlation was found between the applied energy and the size of tumour necrosis at histopathology (Pearson = 0.76, p = 0.002). CONCLUSIONS: Our results show that MR-HIFU ablation with the dedicated breast system is safe and results in histopathologically proven tumour necrosis. KEY POINTS: * MR-HIFU ablation with the dedicated breast system is safe and feasible * In none of the patients was skin redness or burns observed * No correlation was found between the applied energy and the temperature increase * The correlation between applied energy and size of tumour necrosis was good. PMID- 26852220 TI - Differentiation of myocardial ischemia and infarction assessed by dynamic computed tomography perfusion imaging and comparison with cardiac magnetic resonance and single-photon emission computed tomography. AB - OBJECTIVES: To evaluate the feasibility of myocardial blood flow (MBF) by computed tomography from dynamic CT perfusion (CTP) for detecting myocardial ischemia and infarction assessed by cardiac magnetic resonance (CMR) or single photon emission computed tomography (SPECT). METHODS: Fifty-three patients who underwent stress dynamic CTP and either SPECT (n = 25) or CMR (n = 28) were retrospectively selected. Normal and abnormal perfused myocardium (ischemia/infarction) were assessed by SPECT/CMR using 16-segment model. Sensitivity and specificity of CT-MBF (mL/g/min) for detecting the ischemic/infarction and severe infarction were assessed. RESULTS: The abnormal perfused myocardium and severe infarction were seen in SPECT (n = 90 and n = 19 of 400 segments) and CMR (n = 223 and n = 36 of 448 segments). For detecting the abnormal perfused myocardium, sensitivity and specificity were 80 % (95 %CI, 71 90) and 86 % (95 %CI, 76-91) in SPECT (cut-off MBF, 1.23), and 82 % (95 %CI, 76 88) and 87 % (95 %CI, 80-92) in CMR (cut-off MBF, 1.25). For detecting severe infarction, sensitivity and specificity were 95 % (95 %CI, 52-100) and 72 % (95 %CI, 53-91) in SPECT (cut-off MBF, 0.92), and 78 % (95 %CI, 67-97) and 80 % (95 %CI, 58-86) in CMR (cut-off MBF, 0.98), respectively. CONCLUSIONS: Dynamic CTP has a potential to detect abnormal perfused myocardium and severe infarction assessed by SPECT/CMR using comparable cut-off MBF. KEY POINTS: * CT-MBF accurately reflects the severity of myocardial perfusion abnormality. * CT-MBF provides good diagnostic accuracy for detecting myocardial perfusion abnormalities. * CT-MBF may assist in stratifying severe myocardial infarction in abnormal perfusion myocardium. PMID- 26852221 TI - Optic toxicity in radiation treatment of meningioma: a retrospective study in 213 patients. AB - In this retrospective evaluation, we correlated radiation dose parameters with occurrence of optical radiation-induced toxicities. 213 meningioma patients received radiation between 2000 and 2013. Radiation dose and clinical data were extracted from planning systems and patients' files. The range of follow-up period was 2-159 months (median 75 months). Median age of patients was 60 years (range 23-86). There were 163 female and 50 male patients. In 140 cases, at least one of the neuro-optic structures (optic nerves and chiasm) was inside the irradiated target volumes. We found 15 dry eye (7 %) and 24 cataract (11.2 %) cases. Median dose to affected lachrymal glands was 1.47 Gy and median dose to affected lenses was 1.05 Gy. Age and blood cholesterol level in patients with cataract were significantly higher. Patients with dry eye were significantly older. Only two patients with visual problems attributable to radiation treatment were seen. They did not have any risk factors. Maximum and median delivered doses to neuro-optic structures were not higher than 57.30 and 54.60 Gy respectively. Low percentages of cases with radiation induced high grade optic toxicities show that modern treatment techniques and doses are safe. In very few patients with optic side effects, doses to organs at risk were higher than the defined constraint doses. This observation leads to the problem of additional risk factors coming into play. The role of risk factors and safety of higher radiation doses in high grade meningiomas should be investigated in more comprehensive studies. PMID- 26852222 TI - Impact on overall survival of the combination of BRAF inhibitors and stereotactic radiosurgery in patients with melanoma brain metastases. AB - The aim of this study was to evaluate the impact of BRAF inhibitors on survival outcomes in patients receiving stereotactic radiosurgery (SRS) for melanoma brain metastases. We prospectively collected treatment parameters and outcomes for 80 patients with melanoma brain metastases who underwent SRS. Thirty-five patients harbored the BRAF mutation (BRAF-M) and 45 patients did not (BRAF-WT). Univariate and multivariate analyses were performed to identify predictors of overall survival. The median overall survival from first SRS procedure was 6.7, 11.2 months if treated with a BRAF inhibitor and 4.5 months for BRAF-WT. Actuarial survival rates for BRAF-M patients on an inhibitor were 54 % at 6 months and 41 % at 12 months from the time of SRS. In contrast, BRAF-WT had overall survival rates of 28 % at 6 months and 19 % at 12 months. Overall survival was extended for patients on a BRAF inhibitor at or after the first SRS. The median time to intracranial progression was 3.9 months on a BRAF inhibitor and 1.7 months without. The local control rate for all treated tumors was 92.5 %, with no difference based on BRAF status. Patients with higher KPS, fewer treated intracranial metastases, controlled systemic disease, RPA Class 1 and BRAF-M patients had extended overall survival. Overall, patients with BRAF-M treated with both SRS and BRAF inhibitors, at or after SRS, have increased overall survival from the time of SRS. As patients live longer as a result of more effective systemic and local therapies, close surveillance and early management of intracranial disease with SRS will become increasingly important. PMID- 26852223 TI - NAC transcription factors play an important role in ethylene biosynthesis, reception and signaling of tomato fruit ripening. AB - NAC proteins comprise a large family of transcription factors that play important roles in diverse physiological processes during development. To explore the role of NAC transcription factors in the ripening of fruits, we predicted the secondary and tertiary structure as well as regulative function of the SNAC4 (SlNAC48, Accession number: NM 001279348.2) and SNAC9 (SlNAC19, Accession number: XM 004236996.2) transcription factors in tomato. We found that the tertiary structure of SNAC9 was similar to that of ATNAP, which played an important role in the fruit senescence and was required for ethylene stimulation. Likewise, the bio-function prediction results indicated that SNAC4 and SNAC9 participated in various plant hormone signaling and senescence processes. More information about SNACs was obtained by the application of VIGS (virus-induced gene silencing). The silencing of SNAC4 and SNAC9 dramatically repressed the LeACS2, LeACS4 and LeACO1 expression, which consequently led to the inhibition of the ripening process. The silencing of SNACs down-regulated the mRNA levels of the ethylene perception genes and, at the same time, suppressed the expression of ethylene signaling related genes except for LeERF2 which was induced by the silencing of SNAC4. The expressions of LeRIN were different in two silenced fruits. In addition, the silencing of SNAC4 reduced its mRNA level, while the silencing of SNAC9 induced its expression. Furthermore, the silencing of LeACS4, LeACO1 and LeERF2 reduced the expression of SNAC4 and SNAC9, while the silencing of NR induced the expression of all of them. In particular, these results indicate that SNAC transcription factors bind to the promoter of the ethylene synthesis genes in vitro. This experimental evidence demonstrates that SNAC4 and SNAC9 could positively regulate the tomato fruit ripening process by functioning upstream of ethylene synthesis genes. These outcomes will be helpful to provide a theoretical foundation for further exploring the tomato fruit ripening and senescence mechanism. PMID- 26852224 TI - Systematic review of depression in mild traumatic brain injury: study protocol. AB - BACKGROUND: Of the over 1 million reported cases of traumatic brain injuries reported annually in the USA, a sizeable proportion are characterized as mild. Although it is generally well-accepted that most people who suffer a mild traumatic brain injury recover within 1 to 3 months, a proportion of individuals continue to experience physiological, psychological, and emotional symptoms beyond the expected window of recovery. Depression is commonly reported following mild traumatic brain injury; however, its course, consequences, and prognostic factors remain to be well understood. METHODS: A systematic review will be conducted of available prospective longitudinal studies of adult mild traumatic brain injury-related depression. The aim of the systematic review is to describe the course of mild traumatic brain injury-related depression, along with its prognostic factors and health consequences. The review will comply with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A thorough database search of peer-reviewed publications in English and French will be conducted in PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane, Embase, Scopus, Erudit, and Cairn. Independent investigators will perform study selection and data extraction. Risk of bias will be assessed using the Quality in Prognosis Studies tool, and methodological quality will be evaluated using a system inspired by the Scottish Intercollegiate Guidelines Network Methodology. Results will be presented through qualitative description and tabulation. DISCUSSION: This will be the first systematic review conducted with the aim of describing the course, prognostic factors, and health-related outcomes of depression in adults who have suffered a mild traumatic brain injury. The findings of the planned systematic review have the potential to guide research and clinical practice to effectively develop and implement evidence based interventions aimed at preventing and alleviating mild traumatic brain injury-related depression. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015019214. PMID- 26852225 TI - Is adjustment for reporting heterogeneity necessary in sleep disorders? Results from the Japanese World Health Survey. AB - BACKGROUND: Anchoring vignettes are brief texts describing a hypothetical character who illustrates a certain fixed level of a trait under evaluation. This research uses vignettes to elucidate factors associated with sleep disorders in adult Japanese before and after adjustment for reporting heterogeneity in self reports. This study also evaluates the need for adjusting for reporting heterogeneity in the management of sleep and energy related problems in Japan. METHODS: We investigated a dataset of 1002 respondents aged 18 years and over from the Japanese World Health Survey, which collected information through face to-face interview from 2002 to 2003. The ordered probit model and the Compound Hierarchical Ordered Probit (CHOPIT) model, which incorporated anchoring vignettes, were employed to estimate and compare associations of sleep and energy with socio-demographic and life-style factors before and after adjustment for differences in response category cut-points for each individual. RESULTS: The prevalence of self-reported problems with sleep and energy was 53 %. Without correction of cut-point shifts, age, sex, and the number of comorbidities were significantly associated with a greater severity of sleep-related problems. After correction, age, the number of comorbidities, and regular exercise were significantly associated with a greater severity of sleep-related problems; sex was no longer a significant factor. Compared to the ordered probit model, the CHOPIT model provided two changes with a subtle difference in the magnitude of regression coefficients after correction for reporting heterogeneity. CONCLUSION: Sleep disorders are common in the general adult population of Japan. Correction for reporting heterogeneity using anchoring vignettes is not a necessary tool for proper management of sleep and energy related problems among Japanese adults. Older age, gender differences in communicating sleep-related problems, the presence of multiple morbidities, and regular exercise should be the focus of policies and clinical practice to improve sleep and energy management in Japan. PMID- 26852227 TI - Community perceptions of mass screening and treatment for malaria in Siaya County, western Kenya. AB - BACKGROUND: Intermittent mass screening and treatment (iMSaT) is currently being evaluated as a possible additional tool for malaria control and prevention in western Kenya. The literature identifying success and/or barriers to drug trial compliance and acceptability on malaria treatment and control interventions is considerable, especially as it relates to specific target groups, such as school aged children and pregnant women, but there is a lack of such studies for mass screening and treatment and mass drug administration in the general population. METHODS: A qualitative study was conducted to explore community perceptions of the iMSaT intervention, and specifically of testing and treatment in the absence of symptoms, before and after implementation in order to identify aspects of iMSaT that should be improved in future rounds. Two rounds of qualitative data collection were completed in six randomly selected study communities: a total of 36 focus group discussions (FGDs) with men, women, and opinion leaders, and 12 individual or small group interviews with community health workers. All interviews were conducted in the local dialect Dholuo, digitally recorded, and transcribed into English. English transcripts were imported into the qualitative software programme NVivo8 for content analysis. RESULTS: There were mixed opinions of the intervention. In the pre-implementation round, respondents were generally positive and willing to participate in the upcoming study. However, there were concerns about testing in the absence of symptoms including fear of covert HIV testing and issues around blood sampling. There were fewer concerns about treatment, mostly because of the simpler dosing regimen of the study drug (dihydroartemisinin-piperaquine) compared to the current first-line treatment (artemether-lumefantrine). After the first implementation round, there was a clear shift in perceptions with less common concerns overall, although some of the same issues around testing and general misconceptions about research remained. CONCLUSIONS: Although iMSaT was generally accepted throughout the community, proper sensitization activities-and arguably, a more long-term approach to community engagement-are necessary for dispelling fears, clarifying misconceptions, and educating communities on the consequences of asymptomatic malaria. PMID- 26852226 TI - Dual-task performance under acute stress in female adolescents with borderline personality disorder. AB - Research to elucidate early alterations of higher cognitive processes in adolescents with BPD is rare. This study investigated differences in dual-task performance in adolescents with BPD during stress and non-stress conditions. The study sample comprised 30 female adolescents with BPD and 34 healthy controls. The impact of stress on dual-task performance was measured using a standardized stressor. Self-reports of distress and measures of heart rate (HR) were obtained to measure stress reactivity. There were no group differences in task performance. Under stress conditions, the performance on the auditory task decreased in both groups but without significant group differences. Healthy controls showed an increase of mean HR after stress induction compared to no change in the BPD group. The finding of attenuated HR response to acute stress in adolescent patients with BPD may contradict current theories that the affective hyperresponsivity in BPD is based on a biologically determined mechanism. PMID- 26852228 TI - The Enhanced Catalytic Activities of Asymmetric Au-Ni Nanoparticle Decorated Halloysite-Based Nanocomposite for the Degradation of Organic Dyes. AB - Janus particles (JPs) are unique among the nano-/microobjects because they provide asymmetry and can thus impart drastically different chemical or physical properties. In this work, we have fabricated the magnetic halloysite nanotube (HNT)-based HNTs@Fe3O4 nanocomposite (NCs) and then anchored the Janus Au-Ni or isotropic Au nanoparticles (NPs) to the surface of external wall of sulfydryl modified magnetic nanotubes. The characterization by physical methods authenticates the successful fabrication of two different magnetic HNTs@Fe3O4@Au and HNTs@Fe3O4@Au-Ni NCs. The catalytic activity and recyclability of the two NCs have been evaluated considering the degradation of Congo red (CR) and 4 nitrophenol (4-NP) using sodium borohydride as a model reaction. The results reveal that the symmetric Au NPs participated NCs display low activity in the degradation of the above organic dyes. However, a detailed kinetic study demonstrates that the employ of bimetallic Janus Au-Ni NPs in the NCs indicates enhanced catalytic activity, owing to the structurally specific nature. Furthermore, the magnetic functional NCs reported here can be used as recyclable catalyst which can be recovered simply by magnet. PMID- 26852229 TI - Mood stabilizing drugs regulate transcription of immune, neuronal and metabolic pathway genes in Drosophila. AB - RATIONALE: Lithium and valproate (VPA) are drugs used in the management of bipolar disorder. Even though they reportedly act on various pathways, the transcriptional targets relevant for disease mechanism and therapeutic effect remain unclear. Furthermore, multiple studies used lymphoblasts of bipolar patients as a cellular proxy, but it remains unclear whether peripheral cells provide a good readout for the effects of these drugs in the brain. OBJECTIVES: We used Drosophila culture cells and adult flies to analyze the transcriptional effects of lithium and VPA and define mechanistic pathways. METHODS: Transcriptional profiles were determined for Drosophila S2-cells and adult fly heads following lithium or VPA treatment. Gene ontology categories were identified using the DAVID functional annotation tool with a cut-off of p < 0.05. Significantly enriched GO terms were clustered using REVIGO and DAVID functional annotation clustering. Significance of overlap between transcript lists was determined with a Fisher's exact hypergeometric test. RESULTS: Treatment of cultured cells and adult flies with lithium and VPA induces transcriptional responses in genes with similar ontology, with as most prominent immune response, neuronal development, neuronal function, and metabolism. CONCLUSIONS: (i) Transcriptional effects of lithium and VPA in Drosophila S2 cells and heads show significant overlap. (ii) The overlap between transcriptional alterations in peripheral versus neuronal cells at the single gene level is negligible, but at the gene ontology and pathway level considerable overlap can be found. (iii) Lithium and VPA act on evolutionarily conserved pathways in Drosophila and mammalian models. PMID- 26852230 TI - Decreased miR-198 expression and its prognostic significance in human gastric cancer. AB - BACKGROUND: MicroRNAs (miRNAs) have been proved to play important roles in the tumorigenesis and development of human gastric cancer (GC). Our study aims to investigate the expression and clinical significance of miR-198 in GC patients. METHODS: Quantitative real-time polymerase chain reaction (RT-PCR) was performed to evaluate miR-198 levels in 106 pairs of GC specimens and adjacent noncancerous tissues. Then, the associations of miR-198 expression with clinicopathological factors and patient's survival were determined. RESULTS: The expression levels of miR-198 in GC tissues were significantly lower than those in corresponding noncancerous tissues (p<0.01). Decreased miR-198 expression was significantly associated with larger tumor size, deeper invasion depth, positive lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and shorter overall survival. Moreover, multivariate regression analysis identified low miR-198 expression as an independent predictor of poor survival. CONCLUSIONS: These findings suggested that miR-198 downregulation may be associated with progression of GC and that this miR may be an independent prognostic marker for GC patients. PMID- 26852231 TI - Type 2 diabetes enhances arterial uptake of choline in atherosclerotic mice: an imaging study with positron emission tomography tracer 18F-fluoromethylcholine. AB - BACKGROUND: Diabetes is a risk factor for atherosclerosis associated with oxidative stress, inflammation and cell proliferation. The purpose of this study was to evaluate arterial choline uptake and its relationship to atherosclerotic inflammation in diabetic and non-diabetic hypercholesterolemic mice. METHODS: Low density lipoprotein-receptor deficient mice expressing only apolipoprotein B100, with or without type 2 diabetes caused by pancreatic overexpression of insulin like growth factor II (IGF-II/LDLR(-/-)ApoB(100/100) and LDLR(-/-)ApoB(100/100)) were studied. Distribution kinetics of choline analogue (18)F-fluoromethylcholine ((18)F-FMCH) was assessed in vivo by positron emission tomography (PET) imaging. Then, aortic uptakes of (18)F-FMCH and glucose analogue (18)F-fluorodeoxyglucose ((18)F-FDG), were assessed ex vivo by gamma counting and autoradiography of tissue sections. The (18)F-FMCH uptake in atherosclerotic plaques was further compared with macrophage infiltration and the plasma levels of cytokines and metabolic markers. RESULTS: The aortas of all hypercholesterolemic mice showed large, macrophage-rich atherosclerotic plaques. The plaque burden and densities of macrophage subtypes were similar in diabetic and non-diabetic animals. The blood clearance of (18)F-FMCH was rapid. Both the absolute (18)F-FMCH uptake in the aorta and the aorta-to-blood uptake ratio were higher in diabetic than in non diabetic mice. In autoradiography, the highest (18)F-FMCH uptake co-localized with macrophage-rich atherosclerotic plaques. (18)F-FMCH uptake in plaques correlated with levels of total cholesterol, insulin, C-peptide and leptin. In comparison with (18)F-FDG, (18)F-FMCH provided similar or higher plaque-to background ratios in diabetic mice. CONCLUSIONS: Type 2 diabetes enhances the uptake of choline that reflects inflammation in atherosclerotic plaques in mice. PET tracer (18)F-FMCH is a potential tool to study vascular inflammation associated with diabetes. PMID- 26852232 TI - Serum estradiol:oocyte ratio as a predictor of reproductive outcome: an analysis of data from >9000 IVF cycles in the Republic of Ireland. AB - PURPOSE: The purpose of this study was to evaluate the serum estradiol (E2) per oocyte ratio (EOR) as a function of selected embryology events and reproductive outcomes with IVF. METHODS: This retrospective analysis included all IVF cycles where oocyte collection and fresh transfer occurred between January 2001 and November 2012 at a single institution. Patients were divided by three age groups (<35, 35-39, and >=40 years) and further stratified into nine groups based on EOR (measured in pmol/L/oocyte). Terminal serum E2 (pmol/mL) was recorded on day of hCG trigger administration, and fertilization rate, cleavage rate, number of good quality embryos, and reproductive outcomes were recorded for each IVF cycle. RESULTS: During the study interval, 9109 oocyte retrievals were performed for 5499 IVF patients (mean = 1.7 cycles/patient). A total of 63.4 % of transfers were performed on day 3 (n = 4926), while 36.6 % were carried out on day 5 (n = 2843). Clinical pregnancy rates were highest in patients with EOR of 250-750 and declined as this ratio increased, independent of patient age. While the odds ratio (OR) for clinical pregnancy where EOR = 250-750 vs. EOR > 1500 was 3.4 (p < 0.001; 95 % CI 2.67-4.34), no statistically significant correlation was seen in fertilization, cleavage rates or number of good quality embryos as a function of EOR. CONCLUSIONS: Predicting reproductive outcomes with IVF has great utility both for patients and providers. The former have the opportunity to build realistic expectations, and the latter are better able to counsel according to measured clinical parameters. A better understanding of follicular dynamics and ovarian response to gonadotropin stimulation could optimize IVF treatments going forward. PMID- 26852233 TI - A novel technique for in vitro maturation of sheep oocytes in a liquid marble microbioreactor. AB - PURPOSE: The aim of this work was to develop a microbioreactor using liquid marble (LM) as a novel system for oocyte in vitro maturation (IVM) in small volumes. METHODS: Cumulus-oocyte complexes (COCs) obtained from slaughterhouse sheep ovaries were in vitro matured in a LM system prepared by placing a drop (30 MUl containing 10 COCs) suspended in TCM 199 supplemented with 10 % (v/v) oestrus sheep serum (OSS) and 0.1 IU FSH and LH onto a polytetrafluoroethylene (PTFE) particle bed (LM group). As a control group (CTRL group), COCs were in vitro matured in standard volume and conditions (600 MUl of IVM medium in a four-well dish). After 24-h culture at 38.5 degrees C in 5 % CO2 in air, COCs were released from LM and the following parameters were evaluated: (a) percentage of MII oocytes, (b) oocyte developmental competence following in vitro fertilization (IVF) or parthenogenetic activation (PA) and embryo culture for 8 days in synthetic oviductal fluid (SOF) medium at 38.5 degrees C in 5 % O2, 5 % CO2, and 90 % N2. RESULTS: The results indicated similar percentage of MII oocytes in LM and CTRL groups (88.0 vs. 92.0 %). No differences were observed in blastocyst rate after IVF (LM 47.5 % vs. CTRL 50.2 %, P=0.637) or PA (LM 44.4 % vs. CTRL 48.3 %, P=0.426). CONCLUSIONS: The results indicate that LM microbioreactor is a viable technique that provides a suitable microenvironment to induce oocyte in vitro maturation. PMID- 26852234 TI - Late-onset leukoencephalopathy with cerebral calcifications and cysts: case report and review of the literature. AB - BACKGROUND: Leukoencephalopathy with calcifications and cysts (LCC or Labrune disease) is a relatively recently defined and exceptionally rare disease in which parenchymal cysts and calcifications within a widespread leukoencephalopathy can cause a broad spectrum of neurological symptoms. The cause of the disease is unknown. Manifestation is usually in childhood or adolescence, while onset in adulthood has been described in 19 cases. CASE PRESENTATION: Here we report a case of an adult-onset LCC of a Caucasian woman who became symptomatic at age 70 as confirmed by typical neuroimaging and neuropathological findings. After resection of left mesioparietal space-occupying cystic brain tissue the patient has so far remained clinically stable during one year of follow-up with a continuous treatment with glucocorticosteroids. CONCLUSION: To our knowledge this report of a patient who became symptomatic at age 70 represents the oldest age-at onset case of LCC described so far. PMID- 26852235 TI - Coming of Age on the Margins: Mental Health and Wellbeing Among Latino Immigrant Young Adults Eligible for Deferred Action for Childhood Arrivals (DACA). AB - Undocumented immigrant young adults growing up in the United States face significant challenges. For those qualified, the Deferred Action for Childhood Arrivals (DACA) program's protections may alleviate stressors, with implications for their mental health and wellbeing (MHWB). We conducted nine focus groups with 61 DACA-eligible Latinos (ages 18-31) in California to investigate their health needs. Participants reported MHWB as their greatest health concern and viewed DACA as beneficial through increasing access to opportunities and promoting belonging and peer support. Participants found that DACA also introduced unanticipated challenges, including greater adult responsibilities and a new precarious identity. Thus, immigration policies such as DACA may influence undocumented young adults' MHWB in expected and unexpected ways. Research into the impacts of policy changes on young immigrants' MHWB can guide stakeholders to better address this population's health needs. MHWB implications include the need to reduce fear of deportation and increase access to services. PMID- 26852236 TI - Breast Cancer Screening Paved with Good Intentions: Application of the Information-Motivation-Behavioral Skills Model to Racial/Ethnic Minority Women. AB - Racial/ethnic minority women experience disparities in breast cancer. Studies suggest that this may be partly related to later stage of diagnosis. Adherence to breast cancer screening guidelines is frequently lower in racial/ethnic minority populations, which may contribute to this disparity. The purpose of this study was to examine the predictors of intentions to obtain breast cancer screening based on established guidelines using the information-motivation-behavioral skills model. Data for this study were obtained from the community-based Kin KeeperSM Cancer Prevention Intervention study and included 278 racial/ethnic minority women (Black = 138; Latina = 68; Arab = 80). Data were collected between 2009 and 2010 and analyzed in 2013. Structural equation models were tested to examining the effects of functional breast cancer literacy, motivation, and breast cancer screening behavior. Motivation was significantly associated with breast cancer screening. Breast cancer literacy (information) is positively associated with breast cancer screening. The findings indicate that the higher the level of breast cancer literacy and the more motivated patients are, the more likely they are to be screened. In addition, there was a significant association between the covariate race and other model constructs. Functional breast cancer literacy and motivation interventions are important factors to consider when designing breast cancer screening interventions in racial/ethnic minority women. These interventions should consider cultural and contextual factors that are associated with screening behavior. PMID- 26852237 TI - Evaluation of short message service and peer navigation to improve engagement in HIV care in South Africa: study protocol for a three-arm cluster randomized controlled trial. AB - BACKGROUND: In countries with a high burden of HIV, such as South Africa, where the epidemic remains the world's largest, improving early uptake of and consistent adherence to antiretroviral therapy could bring substantial HIV prevention gains. However, patients are not linked to or retained in care at rates needed to curtail the epidemic. Two strategies that have demonstrated a potential to stem losses along the HIV care cascade in the sub-Saharan African context are use of text messaging or short message service (SMS) and peer navigation services. METHODS/DESIGN: We designed a cluster randomized trial to assess the efficacy of an SMS intervention and a peer-navigation intervention to improve retention in care and treatment, timely linkage to care and treatment, medication adherence, and prevention behaviors in South Africa. Eighteen primary and community healthcare clinics in Rustenburg and Moses Kotane Sub-districts in the North West Province were randomized to one of three conditions: SMS intervention (n = 7), peer navigation intervention (n = 7), or standard of care (n = 4). Approximately 42 participants are being recruited at each clinic, which will result in a target of 750 participants. Eligible participants include patients accessing HIV testing or care in a study clinic, recently diagnosed with HIV, aged 18 years or older, and with access to a cellular telephone where they are willing to receive automated SMS with HIV-related messaging. Data collection includes extraction of visit information from clinical files and participant surveys at baseline, 6 months, and 12 months. Intent-to-treat (ITT) analysis will explore differences between randomization arms and the primary outcome of patient retention in care at 12 months following enrollment. We will also explore secondary outcomes including participants' a) timely linkage to care (within 3 months of HIV diagnosis), b) adherence to treatment based on self-report and clinic's medication dispensation dates, and c) condom-use behaviors. DISCUSSION: The findings will allow us to compare the efficacy of two complementary interventions, one that requires fewer resources to implement (SMS) and one (peer navigation) that offers more flexibility in terms of the patient barriers to care that it can address. TRIAL REGISTRATION: NCT02417233, registered 12 December 2014. PMID- 26852238 TI - The influence of dose distribution on treatment outcome in the SCOPE 1 oesophageal cancer trial. AB - PURPOSE: The first aim of this study was to assess plan quality using a conformity index (CI) and analyse its influence on patient outcome. The second aim was to identify whether clinical and technological factors including planning treatment volume (PTV) volume and treatment delivery method could be related to the CI value. METHODS AND MATERIALS: By extending the original concept of the mean distance to conformity (MDC) index, the OverMDC and UnderMDC of the 95 % isodose line (50Gy prescribed dose) to the PTV was calculated for 97 patients from the UK SCOPE 1 trial (ISCRT47718479). Data preparation was carried out in CERR, with Kaplan-Meier and multivariate analysis undertaken in EUCLID and further tests in Microsoft Excel and IBM's SPSS. RESULTS: A statistically significant breakpoint in the overall survival data, independent of cetuximab, was found with OverMDC (4.4 mm, p < 0.05). This was not the case with UnderMDC. There was a statistically significant difference in PTV volume either side of the OverMDC breakpoint (Mann Whitney p < 0.001) and in OverMDC value dependent on the treatment delivery method (mean IMRT = 2.1 mm, mean 3D-CRT = 4.1 mm Mann Whitney p < 0.001). Re-planning the worst performing patients according to OverMDC from 3D-CRT to VMAT resulted in a mean reduction in OverMDC of 2.8 mm (1.6-4.0 mm). OverMDC was not significant in multivariate analysis that included age, sex, staging, tumour type, and position. CONCLUSION: Although not significant when included in multivariate analysis, we have shown in univariate analysis that a patient's OverMDC is correlated with overall survival. OverMDC is strongly related to IMRT and to a lesser extent with PTV volume. We recommend that VMAT planning should be used for oesophageal planning when available and that attention should be paid to the conformity of the 95 % to the PTV. PMID- 26852239 TI - Fructus mume extracts alleviate cognitive impairments in 5XFAD transgenic mice. AB - BACKGROUND: Fructus mume (F. mume) has been used as a traditional treatment for ulcer, cough, and digestive problems for many years in Asian countries. Previous studies have demonstrated that F. mume extracts alleviate cognitive deficits in rats with chronic cerebral hypoperfusion and in mice with scopolamine treatments. The present experiment was conducted to examine the effects of F. mume on cognitive impairments in 5XFAD transgenic mice with five familial Alzheimer's disease (AD) mutations. METHODS: F. mume was administered daily to 5XFAD mice at 12 weeks of age and continued for 90 days. Cognitive function was evaluated using a spatial memory version of the Morris water maze task, the object/location novelty recognition test, and contextual fear conditioning at 24 weeks of age. To elucidate the possible mechanisms underlying the memory improving effects of F. mume in 5XFAD mice, we examined alterations in hippocampal cholinergic function. RESULTS: Vehicle-treated 5XFAD mice exhibited hippocampus-dependent memory impairments compared with non-transgenic littermates, which was reversed in F. mume-treated 5XFAD mice. In addition, reduced hippocampal choline acetyltransferase (ChAT) levels in 5XFAD mice were reversed by F. mume treatment, indicating that F. mume enhances the effects of cholinergic neuronal function. CONCLUSIONS: F. mume may have therapeutic effects on cognitive impairments in AD. PMID- 26852240 TI - Method to represent the distribution of QTL additive and dominance effects associated with quantitative traits in computer simulation. AB - BACKGROUND: Computer simulation is a resource which can be employed to identify optimal breeding strategies to effectively and efficiently achieve specific goals in developing improved cultivars. In some instances, it is crucial to assess in silico the options as well as the impact of various crossing schemes and breeding approaches on performance for traits of interest such as grain yield. For this, a means by which gene effects can be represented in the genome model is critical. RESULTS: To address this need, we devised a method to represent the genomic distribution of additive and dominance gene effects associated with quantitative traits. The method, based on meta-analysis of previously-estimated QTL effects following Bennewitz and Meuwissen (J Anim Breed Genet 127:171-9, 2010), utilizes a modified Dirichlet process Gaussian mixture model (DPGMM) to fit the number of mixture components and estimate parameters (i.e. mean and variance) of the genomic distribution. The method was demonstrated using several maize QTL data sets to provide estimates of additive and dominance effects for grain yield and other quantitative traits for application in maize genome simulations. CONCLUSIONS: The DPGMM method offers an alternative to the over-simplified infinitesimal model in computer simulation as a means to better represent the genetic architecture of quantitative traits, which likely involve some large effects in addition to many small effects. Furthermore, it confers an advantage over other methods in that the number of mixture model components need not be known a priori. In addition, the method is robust with use of large-scale, multi allelic data sets or with meta-analyses of smaller QTL data sets which may be derived from bi-parental populations in precisely estimating distribution parameters. Thus, the method has high utility in representing the genetic architecture of quantitative traits in computer simulation. PMID- 26852241 TI - Coronary arteries anomalous aortic origin on a computed tomography angiography population: prevalence, characteristics and clinical impact. AB - Anomalous aortic origin of coronary arteries (AAOCA) is one of the most frequent causes of cardiovascular sudden death among the young population. We aimed to determine the prevalence and anatomic characteristics of AAOCA in a population referred to computed tomography angiography (CTA) and to describe the clinical prognosis of these findings at middle term follow-up. From a total of 3539 CTA, 53 were found to have AAOCA. This population was compared to an age and gender matched control group (n = 106) from the same CTA list. A telephone follow-up to determine cardiac events was conducted, with a mean follow-up of 45.9 +/- 28.2 months. Prevalence of AAOCA was 1.5 %. The most common AAOCA was an origin of the right coronary artery (RCA) from the left coronary sinus, followed by an origin of the left circumflex artery (LCX) arising from the right coronary sinus. All patients with an anomalous origin of the RCA had an interarterial course. Four additional patients were found to have an interarterial course: 1 with an anomalous origin of LCX and 3 with an anomalous origin of the left main coronary artery (LMCA). At follow-up there were 33 (21.2 %) cardiac events, 9 (17.6 %) on the AAOCA group and 24 (22.9 %) on the control group (p = 0.46). Cardiac events and cardiovascular deaths were not related to any particular AAOCA or to interarterial courses. Among an adult population referred to CTA, AAOCA were not related with worse middle term prognosis when compared to an age- and gender- matched population. PMID- 26852242 TI - Assessment of aortic stiffness among patients with systemic lupus erythematosus and rheumatoid arthritis by magnetic resonance imaging. AB - To evaluate aortic stiffness by MRI in female patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in comparison to controls. We measured aortic strain, distensibility and pulse wave velocity (PWV) by MRI in 30 SLE patients, 31 RA patients and 53 matched controls. Mean PWV in SLE and RA patients were higher in comparison to controls (9.2 +/- 4.4 vs. 7.6 +/- 3.0 m/s, p = 0.04) and (6.2 +/- 2.3 vs. 5.4 +/- 1.7, p = 0.04) respectively. Aortic distensibility among RA patients was significantly lower in comparison to controls (4.4 +/- 4.6 vs. 5.8 +/- 4.9 kPa(-1) * 10(-3), p = 0.04). A significant correlation was found between PWV and age (r = 0.67, p < 0.001), Framingham risk score (r = 0.61, p < 0.001), waist to hip ratio (r = 0.45, p < 0.001), systolic blood pressure (r = 0.37, p = 0.01), diabetes (r = 0.32, p = 0.001) and dyslipidemia (r = 0.32, p = 0.001). In multivariate analysis for the prediction of PWV, variables which were found significant included: RA (p = 0.01), age (p < 0.001) and hypertension (p = 0.01) for patients with RA and SLE (p = 0.02), waist to hip ratio (p < 0.001) and total cholesterol (p < 0.001) for patients with SLE. Arterial stiffness, characterized by metrics of aortic distensibility and pulse wave velocity derived from MRI, is increased in SLE and RA female patients. PMID- 26852245 TI - Model-based roentgen stereophotogrammetric analysis of the surface replacement trapeziometacarpal total joint arthroplasty. AB - : The primary aim of this clinical and radiostereometric study was to study the migration pattern of the surface replacement trapeziometacarpal joint prosthesis (SRTMTMC, Avanta(r), San Diego, CA). The secondary aims were to assess patient related outcomes and prosthesis survival 5 years after surgery. Ten patients received the prosthesis. Radiostereometric radiographs were obtained 6 weeks, 6 months, 1 year and 5 years post-operatively and were analysed using model-based software. All patients completed DASH and Nelson Hospital scores at these follow ups. Mean translations varied between 0.0 and 0.5 mm after 5 years. Rotation values could be calculated in six patients and mean rotations varied between -0.3 and 2.3 degrees , although the precision of rotation values seems to be poor. The 5-year survival rate was 80%. Mean pre-operative DASH and Nelson Hospital scores were 53 (SD 14) and 51 (SD 13), respectively. Six months post-operatively, the DASH and Nelson Hospital scores had both significantly improved to 25 (SD 20) and 74 (SD 18) and remained high after 5 years. Implant stability was good 5 years post-operatively, and early migration did not predict implant failure in this study. LEVEL OF EVIDENCE: IV. PMID- 26852244 TI - Individualized radiotherapy by combining high-end irradiation and magnetic resonance imaging. AB - Image-guided radiotherapy (IGRT) has been integrated into daily clinical routine and can today be considered the standard especially with high-dose radiotherapy. Currently imaging is based on MV- or kV-CT, which has clear limitations especially in soft-tissue contrast. Thus, combination of magnetic resonance (MR) imaging and high-end radiotherapy opens a new horizon. The intricate technical properties of MR imagers pose a challenge to technology when combined with radiation technology. Several solutions that are almost ready for routine clinical application have been developed. The clinical questions include dose escalation strategies, monitoring of changes during treatment as well as imaging without additional radiation exposure during treatment. PMID- 26852243 TI - Unilateral and bilateral neck SIB for head and neck cancer patients : Intensity modulated proton therapy, tomotherapy, and RapidArc. AB - AIM: To compare simultaneous integrated boost plans for intensity-modulated proton therapy (IMPT), helical tomotherapy (HT), and RapidArc therapy (RA) for patients with head and neck cancer. PATIENTS AND METHODS: A total of 20 patients with squamous cell carcinoma of the head and neck received definitive chemoradiation with bilateral (n = 14) or unilateral (n = 6) neck irradiation and were planned using IMPT, HT, and RA with 54.4, 60.8, and 70.4 GyE/Gy in 32 fractions. Dose distributions, coverage, conformity, homogeneity to planning target volumes (PTV)s and sparing of organs at risk and normal tissue were compared. RESULTS: All unilateral and bilateral plans showed excellent PTV coverage and acceptable dose conformity. For unilateral treatment, IMPT delivered substantially lower mean doses to contralateral salivary glands (< 0.001-1.1 Gy) than both rotational techniques did (parotid gland: 6-10 Gy; submandibular gland: 15-20 Gy). Regarding the sparing of classical organs at risk for bilateral treatment, IMPT and HT were similarly excellent and RA was satisfactory. CONCLUSION: For unilateral neck irradiation, IMPT may minimize the dry mouth risk in this subgroup but showed no advantage over HT for bilateral neck treatment regarding classical organ-at-risk sparing. All methods satisfied modern standards regarding toxicity and excellent target coverage for unilateral and bilateral treatment of head and neck cancer at the planning level. PMID- 26852246 TI - Symptomatic Versus Asymptomatic Colorectal Cancer: Predictive Features at CT Colonography. AB - RATIONALE AND OBJECTIVES: Computed tomographic colonography (CTC) is a robust tool for evaluating colorectal lesions in both screening and diagnostic settings. The purpose of this study was to assess the relationship between colorectal cancer (CRC) tumor characteristics and patient symptomatology. MATERIALS AND METHODS: This is a retrospective analysis of all pathology-confirmed cases of CRC evaluated with CTC at our institution from October 2004 to October 2012. Cases were reviewed to determine tumor size, morphology, and degree of luminal narrowing. An electronic medical record review was performed to delineate specific patient symptomatology and determine depth of invasion. RESULTS: A total of 55 patients (36 symptomatic and 19 asymptomatic) with a total of 63 CRCs were evaluated by CTC during the study time period. The most common symptoms were gastrointestinal (GI) bleeding/anemia (n = 26), followed by obstructive symptoms (n = 23), and constitutional symptoms (n = 5). Symptomatic cancers were more likely to have annular morphology (n = 30/43, 70% vs. n = 3/20, 15%; odds ratio [OR] = 13.1, P = 0.0003), whereas asymptomatic cancers were more likely to be polypoid (n = 11/20, 55% vs. n = 6/43, 14%, OR = 7.5, P = 0.001). Symptomatic cancers were also larger (46.1 +/- 22.4 vs. 38.8 +/- 18.4 mm, P = 0.005) and resulted in greater luminal narrowing (8.7 +/- 8.5 mm vs. 35.8 +/- 18.8 mm, P < 0.0001) with deeper invasion (n = 29/35 [invasion unknown for 8 cases], 83% vs. n = 6/20, 30%, OR = 11.3, P = 0.0003). Invasive cancers were more likely to have annular morphology (66%, 23/25, P = 0.002). CONCLUSIONS: There is an intuitive and predictable relationship between tumor characteristics on CTC and patient symptoms. Annular morphology, tumor size, degree of luminal narrowing, and invasive disease all correlate with the presence of symptoms. PMID- 26852247 TI - Perfusion Parameters in Dynamic Contrast-enhanced MRI and Apparent Diffusion Coefficient Value in Diffusion-weighted MRI:: Association with Prognostic Factors in Breast Cancer. AB - RATIONALE AND OBJECTIVES: To evaluate the association of prognostic factors and subtypes of breast cancer with perfusion parameters in dynamic contrast-enhanced magnetic resonance imaging and apparent diffusion coefficient (ADC) values in diffusion-weighted magnetic resonance imaging. MATERIALS AND METHODS: Quantitative perfusion parameters (constant of transfer from plasma to interstitium, constant of transfer from the interstitium to the plasma, extravascular/extracellular volume per unit of volume of tissue [ve], and initial area under the concentration curve [iAUC]) and ADC values in the entire tumor volume of 52 invasive ductal carcinomas were obtained using histogram analysis. Four measures (25th percentile, mean, median, 75th percentile) were calculated for each parameter and the ADC value. Associations of perfusion parameters and ADC values with prognostic factors and tumor subtypes were analyzed. RESULTS: Among perfusion parameters, iAUCmean and iAUCmedian were greater in tumors larger than 2 cm (8.23 +/- 2.33, 8.64 +/- 2.67 * 10(4)) than in those smaller than 2 cm (6.99 +/- 1.92, 7.04 +/- 2.15 * 10(4); P = 0.046, 0.023). Ve median was higher in tumors with progesterone receptor (PR) positivity (0.54 +/- 0.18) than in those with PR negativity (0.44 +/- 0.1, P = 0.041). There were higher ADCmean and ADCmedian in tumors with human epidermal growth factor receptor 2 (HER2) positivity (1.306 and 1.278 * 10(-3)mm(2)/s) than in those with HER2 negativity (1.078 and 1.053 * 10(-3)mm(2)/s; P = 0.012 and 0.020). Higher ADCmean and ADCmedian were observed in HER2-enriched type (1.404 and 1.378 * 10(-3)mm(2)/s) than in luminal type (1.096 and 1.073 * 10(-3)mm(2)/s; P = 0.030 and 0.045). CONCLUSIONS: Among perfusion parameters, iAUC was associated with tumor size and ve median was associated with PR positivity. Mean and median ADC values showed positive correlation with HER2-positive and HER2-enriched tumors. PMID- 26852248 TI - Comparison of Measured and Estimated CT Organ Doses for Modulated and Fixed Tube Current:: A Human Cadaver Study. AB - RATIONALE AND OBJECTIVES: The aim of this study was to compare the directly measured and the estimated computed tomography (CT) organ doses obtained from commercial radiation dose-tracking (RDT) software for CT performed with modulated tube current or automatic exposure control (AEC) technique and fixed tube current (mAs). MATERIALS AND METHODS: With the institutional review board (IRB) approval, the ionization chambers were surgically implanted in a human cadaver (88 years old, male, 68 kg) in six locations such as liver, stomach, colon, left kidney, small intestine, and urinary bladder. The cadaver was scanned with routine abdomen pelvis protocol on a 128-slice, dual-source multidetector computed tomography (MDCT) scanner using both AEC and fixed mAs. The effective and quality reference mAs of 100, 200, and 300 were used for AEC and fixed mAs, respectively. Scanning was repeated three times for each setting, and measured and estimated organ doses (from RDT software) were recorded (N = 3*3*2 = 18). RESULTS: Mean CTDIvol for AEC and fixed mAs were 4, 8, 13 mGy and 7, 14, 21 mGy, respectively. The most estimated organ doses were significantly greater (P < 0.01) than the measured organ doses for both AEC and fixed mAs. At AEC, the mean estimated organ doses (for six organs) were 14.7 mGy compared to mean measured organ doses of 12.3 mGy. Similarly, at fixed mAs, the mean estimated organ doses (for six organs) were 24 mGy compared to measured organ doses of 22.3 mGy. The differences among the measured and estimated organ doses were higher for AEC technique compared to the fixed mAs for most organs (P < 0.01). CONCLUSIONS: The most CT organ doses estimated from RDT software are greater compared to directly measured organ doses, particularly when AEC technique is used for CT scanning. PMID- 26852249 TI - Harm Reduction or Harm Introduction? Prevalence and Correlates of E-Cigarette Use Among French Adolescents. AB - PURPOSE: Electronic cigarettes are marketed as a tool to give up or reduce cigarette smoking, and their use has risen sharply in recent years. There is concern that use is increasing particularly among adolescents and that they are not being used as a cessation tool but as a novel experience in their own right. METHODS: The present research assessed prevalence and sociodemographic correlates of e-cigarette use and standard cigarette use and also explored the extent to which e-cigarettes appear to be used as a cessation tool. This was assessed using a questionnaire administered to 1,486 French adolescents aged 16 years. RESULTS: Prevalence of e-cigarette experimentation was high (54%) and comparable to that for standard cigarettes (55%). Furthermore, 20% of those who had experimented with e-cigarettes had never tried standard cigarettes, and among regular smokers of standard cigarettes, intentions to quit were not associated with e-cigarette usage frequency. Experimentation with both e-cigarettes and standard cigarettes was significantly predicted by higher age, higher socioeconomic status, and parental smoking of standard cigarettes (in particular the father). Being male marginally predicted e-cigarette use, whereas being female significantly predicted standard cigarette use. CONCLUSIONS: These findings give cause for concern: e-cigarette usage experimentation is extremely high, and is not associated with attempts to quit smoking standard cigarettes. Rather, it is exposing adolescents to a highly addictive drug (nicotine) and may pave the way for a future cigarette habit. PMID- 26852250 TI - Choice of Postpartum Contraception: Factors Predisposing Pregnant Adolescents to Choose Less Effective Methods Over Long-Acting Reversible Contraception. AB - PURPOSE: The purposes were to determine contraceptive methods pregnant adolescents intend to use postpartum and to understand factors that predispose intention to use less effective birth control than long-acting reversible contraception (LARC). METHODS: Participants were 247 pregnant minority adolescents in a prenatal program. Intention was assessed by asking "Which of the following methods of preventing pregnancy do you intend to use after you deliver?" Multinomial logistic regression analysis was used to determine factors associated with intent to use nonhormonal (NH) contraception (male/female condoms, abstinence, withdrawal and no method) or short-/medium-acting hormonal (SMH) contraception (birth control pill, patch, vaginal ring, injectable medroxyprogesterone acetate) compared with LARC (implant and intrauterine device) postpartum. RESULTS: Twenty-three percent intended to use LARC, 53% an SMH method, and 24% an NH method. Participants who intended to use NH or SMH contraceptive methods over LARC were significantly more likely to believe that LARC is not effective at preventing pregnancy, to report that they do not make decisions to help reach their goals and that partners are not important when making contraceptive decisions. Other important factors were having a mother who was aged >19 years at first birth and had not graduated from high school, not having experienced a prior pregnancy or talked with parents about birth control options, and the perception of having limited financial resources. CONCLUSIONS: Distinct profiles of factors associated with intending to use NH or SMH contraceptive methods over LARC postpartum were identified and may inform future interventions to promote the use of LARC to prevent repeat pregnancy. PMID- 26852252 TI - Adsorptive removal of arsenate from aqueous solutions by biochar supported zero valent iron nanocomposite: Batch and continuous flow tests. AB - Arsenate (As(V)) removal ability by nanoscale zero-valent iron (nZVI) is compromised by aggregation of nZVI particles. In this work, pine derived biochar (PB) was used as a supporting material to stabilize nZVI for As(V) removal. The biochar supported nZVI (nZVI/BC) was synthesized by precipitating the nanoparticles on carbon surfaces. Experiments using batch and continuous flow, completely mixed reactors (CMRs) were carried out to investigate the removal of As(V) by the nZVI/BC from aqueous solutions. Batch experiments showed that nZVI/BC had high As(V) removal capacity in a wide range of pH (3-8). Kinetic data revealed that equilibrium was reached within 1h and the isotherm data showed that the Langmuir maximum adsorption capacity of the nZVI/BC for As(V) at pH 4.1 was 124.5gkg-1. As(V) (100mgL-1) adsorption in anoxic condition was about 8% more than in oxic conditions, where As(V) reduction was observed in anoxic condition. The performance of the nZVI/BC in flowing condition was evaluated in CMRs at influent As(V) concentrations of 2.1 and 5.5mgL-1 and the adsorbent removed 100% and 90% of the As(V), respectively. Furthermore, the nZVI/BC composite is magnetic which facilitates collection from aqueous solutions. PMID- 26852251 TI - New adipokines. AB - Adipose tissue is now widely recognized as "an organ" able to synthesize and secrete hundred factors collectively called adipokines. These secreted molecules exert pleiotropic actions, notably on the regulation of glucose and lipid metabolism, inflammation, reproduction, or angiogenesis. Over the past two decades, a considerable amount of work was performed on the two "star" adipokines, leptin and adiponectin, particularly because of their involvement in energy metabolism. The present review is focused on the three most recently discovered adipokines that are clearly emerging as important actors in metabolism: apelin, fibroblast growth factor-21, and neuroregulin-4. Moreover, given a number of clinical and experimental data, these three adipokines represent promising targets in the context of metabolic disorders associated with obesity. PMID- 26852253 TI - Evaluation of monovalent and multivalent iminosugars to modulate Candida albicans beta-1,2-mannosyltransferase activities. AB - beta-1,2-Linked oligomannosides substitute the cell wall of numerous yeast species. Several of those including Candida albicans may cause severe infections associated with high rates of morbidity and mortality, especially in immunocompromised patients. beta-1,2-Mannosides are known to be involved in the pathogenic process and to elicit an immune response from the host. In C. albicans, the synthesis of beta-mannosides is under the control of a family of nine genes coding for putative beta-mannosyltransferases. Two of them, CaBmt1 and CaBmt3, have been shown to initiate and prime the elongation of the beta mannosides on the cell-wall mannan core. In the present study, we have assessed the modulating activities of monovalent and multivalent iminosugar analogs on these enzymes in order to control the enzymatic bio-synthesis of beta-mannosides. We have identified a monovalent deoxynojirimycin (DNJ) derivative that inhibits the CaBmt1-catalyzed initiating activity, and mono-, tetra- and polyvalent deoxymannojirimycin (DMJ) that modulate the CaBmt1 activity toward the formation of a single major product. Analysis of the aggregating properties of the multivalent iminosugars showed their ability to elicit clusterization of both CaBmt1 and CaBmt3, without affecting their activity. These results suggest promising roles for multivalent iminosugars as controlling agents for the biosynthesis of beta-1,2 mannosides and for monovalent DNJ derivative as a first target for the design of future beta-mannosyltransferase inhibitors. PMID- 26852254 TI - Postpartum Hemorrhage Preparedness Elements Vary Among Hospitals in New Jersey and Georgia. AB - OBJECTIVE: To identify the presence or absence of 38 postpartum hemorrhage preparedness elements in hospitals in New Jersey and Georgia as a component of the Postpartum Hemorrhage Project of the Association of Women's Health, Obstetric and Neonatal Nurses. DESIGN: Quality improvement baseline assessment survey. SETTING: Hospitals (N = 95) in New Jersey and Georgia. PARTICIPANTS: Key informants were clinicians who were members of their hospitals' obstetric teams and were recognized as knowledgeable about their hospitals' postpartum hemorrhage policies. METHODS: An electronic survey was sent by e-mail to each identified hospital's key informant. RESULTS: The mean number of elements present was 23.1 (SD = 5.2; range = 12-34). Volume of births, students, magnet status, and other hospital characteristics did not predict preparedness. None of the hospitals had all of the 38 preparedness elements available. Less than 50% of the hospitals had massive hemorrhage protocols, performed risk assessments and drills, or measured blood loss. For every 10% increase in the total percentage of African American women who gave birth, there was a decrease of one preparedness element. CONCLUSION: Objective measures of preparedness are needed, because perceptions of preparedness were inconsistent with the number of preparedness elements reported. PMID- 26852255 TI - Causes, diagnosis, and treatment of central precocious puberty. AB - Central precocious puberty results from the premature activation of the hypothalamic-pituitary-gonadal axis. It mimics physiological pubertal development, although at an inappropriate chronological age (before 8 years in girls and 9 years in boys). It can be attributable to cerebral congenital malformations or acquired insults, but the cause in most cases in girls remains unknown. MKRN3 gene defects have been identified in familial disease, with important basic and clinical results. Indeed, genetic analysis of this gene should be included in the routine clinical investigation of familial and idiopathic cases of central precocious puberty. Gonadotropin-releasing hormone agonists are the gold-standard treatment. The assessment and management of this disease remain challenging for paediatric endocrinologists. In this Series paper, we describe current challenges involving the precise diagnosis and adequate treatment of this disorder. PMID- 26852257 TI - Industry view on the relative importance of "clonality" of biopharmaceutical producing cell lines. AB - Recently, several health authorities have requested substantial detail from sponsor firms regarding the practices employed to generate the production cell line for recombinant DNA-(rDNA) derived biopharmaceuticals. Two possible inferences from these regulatory agency questions are that (1) assurance of "clonality" of the production cell line is of major importance to assessing the safety and efficacy of the product and (2), without adequate proof of "clonality", additional studies of the cell line and product are often required to further ensure the product's purity and homogeneity. Here we address the topic of "clonality" in the broader context of product quality assurance by current technologies and practices, as well as discuss some of the relevant science and historical perspective. We agree that the clonal derivation of a production cell line is one factor with potential impact, but it is only one of many factors. Further, we believe that regulatory emphasis should be primarily placed on ensuring product quality of the material actually administered to patients, and on ensuring process consistency and implementing appropriate control strategies through the life cycle of the products. PMID- 26852258 TI - Phytomedicines for Helicobacter pylori, Garlic for Hypertension, Intraoperative Acupuncture for Tonsillectomy, Omega-3 Fatty Acids for Cognitive Decline, Qigong for COPD. PMID- 26852259 TI - Draft genome sequence of Shimia marina CECT 7688(T). AB - Shimia marina is a member of the family Rhodobacteraceae described in 2006. Strain CL-TA03(T) (=CECT 7688(T)) was isolated from a biofilm formed on an acrylic slide submerged in surface water in a coastal fish farm in Tongyeong, Korea. Here we report the draft genome sequence and annotation of S. marina CECT 7688(T) which is composed by 4,001,860bp arranged in 45 scaffolds with a G+C content of 57.4%, 3878 protein coding genes, 40 tRNA genes, 4 rRNA genes and 1 repeat region. An overview of annotated genes revealed diverse genes encoding for exopolysaccharide and capsular biosynthesis enzymes, secondary metabolite biosynthesis enzymes, multiple antibiotic and metal resistance and the ability for degrading aromatic compounds. PMID- 26852256 TI - Pubertal development and regulation. AB - Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The hypothalamic-pituitary-gonadal axis controls puberty and reproduction and is tightly regulated by a complex network of excitatory and inhibitory factors. This axis is active in the embryonic and early postnatal stages of life and is subsequently restrained during childhood, and its reactivation culminates in puberty initiation. The mechanisms underlying this reactivation are not completely known. The age of puberty onset varies between individuals and the timing of puberty initiation is associated with several health outcomes in adult life. In this Series paper, we discuss pubertal markers, epidemiological trends of puberty initiation over time, and the mechanisms whereby genetic, metabolic, and other factors control secretion of gonadotropin releasing hormone to determine initiation of puberty. PMID- 26852261 TI - Concern over Zika virus grips the world. PMID- 26852260 TI - Unique immunomodulatory effect of paeoniflorin on type I and II macrophages activities. AB - It has been widely accepted that macrophages are divided into M1 "pro inflammatory" macrophages and M2 "anti-inflammatory" macrophages and an uncontrolled macrophage polarization plays an important role in the pathogenesis of different diseases. As the main substance of total glucosides of peony, paeoniflorin (PF), has been widely used to treat autoimmune and autoinflammatory diseases for years. Mechanistically, PF has been found to alter activities of many immune cells, which could further reduce inflammation and tissue damage. However, whether and how PF affects macrophages activities in vitro remains unknown. In current study, using M1 and M2 cells generated from mouse bone marrow precursors, we explored the role of PF in regulating M1/M2 cells activity in vitro. The results showed that PF inhibited LPS-induced M1 activity by reducing iNOS expression and NO production via decreasing LPS/NF-kappaB signaling pathway; whereas, PF enhanced IL-4-provoked M2 function by up-regulating Arg-1 production and activity via increasing IL-4/STAT6 signaling pathway. Our new finding indicates that PF can suppress M1 cells activity and enhance M2 cells function simultaneously, which could help to ameliorate autoimmune and autoinflammatory diseases in clinical treatment. PMID- 26852262 TI - Tackling cancer: time for a global response. PMID- 26852263 TI - Increasing worldwide access to medical opioids. PMID- 26852264 TI - Use of and barriers to access to opioid analgesics: a worldwide, regional, and national study. AB - BACKGROUND: Despite opioid analgesics being essential for pain relief, use has been inadequate in many countries. We aim to provide up-to-date worldwide, regional, and national data for changes in opioid analgesic use, and to analyse the relation of impediments to use of these medicines. METHODS: We calculated defined daily doses for statistical purposes (S-DDD) per million inhabitants per day of opioid analgesics worldwide and for regions and countries from 2001 to 2013, and we used generalised estimating equation analysis to assess longitudinal change in use. We compared use data against the prevalence of some health disorders needing opioid use. We surveyed 214 countries or territories about impediments to availability of these medicines, and used regression analyses to establish the strength of associations between impediments and use. FINDINGS: The S-DDD of opioid analgesic use more than doubled worldwide between 2001-03 and 2011-13, from 1417 S-DDD (95% CI -732 to 3565; totalling about 3.01 billion defined daily doses per annum) to 3027 S-DDD (-1162 to 7215; totalling about 7.35 billion defined daily doses per annum). Substantial increases occurred in North America (16,046 S-DDD [95% CI 4032-28,061] to 31,453 S-DDD [8121-54,785]), western and central Europe (3079 S-DDD [1274-4883] to 9320 S-DDD [3969-14,672]), and Oceania (2275 S-DDD [763-3787] to 9136 S-DDD [2508-15,765]). Countries in other regions have shown no substantial increase in use. Impediments to use included an absence of training and awareness in medical professionals, fear of dependence, restricted financial resources, issues in sourcing, cultural attitudes, fear of diversion, international trade controls, and onerous regulation. Higher number of impediments reported was significantly associated with lower use (unadjusted incidence rate ratio 0.39 [95% CI 0.29-0.52]; p<0.0001), but not when adjusted for gross domestic product and human development index (0.91 [0.73-1.14]; p=0.4271). INTERPRETATION: Use of opioid analgesics has increased, but remains low in Africa, Asia, Central America, the Caribbean, South America, and eastern and southeastern Europe. Identified impediments to use urgently need to be addressed by governments and international agencies. FUNDING: International Narcotics Control Board, UN. PMID- 26852265 TI - Application of l-cystine modified zeolite for preconcentration and determination of ultra-trace levels of cadmium by flame atomic absorption spectrometry. AB - A very convenient, sensitive and precise solid phase extraction (SPE) system was developed for enrichment and determination of ultra-trace of cadmium ion in water and plant samples. This method was based on the retention of cadmium(II) ions by l-cystine adsorbed in Y-zeolite and carry out in a packed mini-column. The retained cadmium ions then were eluted and determined by flame atomic absorption spectrometry. The scanning electron microscopy (SEM), powder X-ray diffraction (XRD) and Fourier Transform Infrared (FT-IR) spectroscopy techniques were applied for the characterization of cystine modified zeolite (CMZ). Some experimental conditions affecting the analytical performance such as pH, eluent type, concentration of sample, eluent flow rate and also the presence of interfering ions were investigated. The calibration graph was linear within the range of 0.1 7.5ngmL(-1) and limit of detection was obtained 0.04ngmL(-1) with the preconcentration factor of 400. The relative standard deviation (RSD) was obtained 1.4%, indicating the excellent reproducibility of this method. The proposed method was successfully applied for the extraction and determination of cadmium(II) ion in black tea, cigarette's tobacco and also various water samples. PMID- 26852266 TI - Improving permeability and chromatographic performance of poly(pentaerythritol diacrylate monostearate) monolithic column via photo-induced thiol-acrylate polymerization. AB - A simple approach was developed for rapid preparation of polymeric monolithic columns in UV-transparent fused-silica capillaries via photoinitiated thiol acrylate polymerization of pentaerythritol diacrylate monostearate (PEDAS) and trimethylolpropane tris(3-mercaptopropionate) (TPTM) within 10min, in which the acrylate homopolymerized and copolymerized with the thiol simultaneously. The morphology, permeability and chromatographic performance of the resulting poly(PEDAS-co-TPTM) monoliths were studied. It could be observed from SEM that the morphology of poly(PEDAS-co-TPTM) monolith was rather different from that of poly(PEDAS) monolith, which was fabricated via photo-induced free radical polymerization using PEDAS as the sole monomer. Compared with poly(PEDAS) monolith, poly(PEDAS-co-TPTM) monolith possessed better permeability when they were fabricated under the same preparation conditions. By adjusting the composition of porogenic solvents, poly(PEDAS-co-TPTM) monolith exhibited lower plate heights (15.7-17.7MUm) than poly(PEDAS) monolith (19.1-37.9MUm) in MULC. In addition, 66 unique peptides were positively identified on poly(PEDAS-co-TPTM) monolith when tryptic digest of four proteins was separated by MULC-MS/MS, demonstrating its potential in proteome analysis. PMID- 26852267 TI - Impaired anterior swim bladder inflation following exposure to the thyroid peroxidase inhibitor 2-mercaptobenzothiazole part I: Fathead minnow. AB - In the present study, a hypothesized adverse outcome pathway linking inhibition of thyroid peroxidase (TPO) activity to impaired swim bladder inflation was investigated in two experiments in which fathead minnows (Pimephales promelas) were exposed to 2-mercaptobenzothiazole (MBT). Continuous exposure to 1mg MBT/L for up to 22 days had no effect on inflation of the posterior chamber of the swim bladder, which typically inflates around 6 days post fertilization (dpf), a period during which maternally-derived thyroid hormone is presumed to be present. In contrast, inflation of the anterior swim bladder, which occurs around 14dpf, was impacted. Specifically, at 14dpf, approximately 50% of fish exposed to 1mg MBT/L did not have an inflated anterior swim bladder. In fish exposed to MBT through 21 or 22dpf, the anterior swim bladder was able to inflate, but the ratio of the anterior/posterior chamber length was significantly reduced compared to controls. Both abundance of thyroid peroxidase mRNA and thyroid follicle histology suggest that fathead minnows mounted a compensatory response to the presumed inhibition of TPO activity by MBT. Time-course characterization showed that fish exposed to MBT for at least 4 days prior to normal anterior swim bladder inflation had significant reductions in anterior swim bladder size, relative to the posterior chamber, compared to controls. These results, along with similar results observed in zebrafish (see part II, this issue) are consistent with the hypothesis that thyroid hormone signaling plays a significant role in mediating anterior swim bladder inflation and development in cyprinids, and that role can be disrupted by exposure to thyroid hormone synthesis inhibitors. Nonetheless, possible thyroid-independent actions of MBT on anterior swim bladder inflation cannot be ruled out based on the present results. Overall, although anterior swim bladder inflation has not been directly linked to survival as posterior swim bladder inflation has, potential links to adverse ecological outcomes are plausible given involvement of the anterior chamber in sound production and detection. PMID- 26852269 TI - Widespread metachronous carcinoid tumour metastases to the head and neck: a unique presentation. AB - Carcinoid tumours are usually slow-growing, neuroendocrine neoplasms that primarily affect the gastrointestinal tract and bronchial tree. Although relatively rare, isolated, single metastasis to the head and neck has been reported. We present a unique case of 6 metachronous carcinoid metastases to both parotid glands, the left submandibular gland, upper lip, and thyroid, over 3 years. To our knowledge, this widespread presentation in the head and neck has not previously been reported. PMID- 26852270 TI - Validation of a technique for integration of a digital dental model into stereophotogrammetric images of the face using cone-beam computed tomographic data. AB - We wanted to find and validate a new way to visualise patients' faces and their dental arches non-invasively. The stereophotogrammetric images of the faces and the digitised dental casts of seven healthy subjects were analysed. Point-based and surface-based recording techniques matched the facial image with those of the mandibular and maxillary dental arches in their relative positions. The cone-beam computed tomographic (CT) images of the same subjects were analysed retrospectively. Twenty-eight dentofacial distances were obtained on cone-beam CT images and on the recorded facial and dental surfaces. The median (IQR) distances of more than 96% of the measurements did not differ significantly. PMID- 26852271 TI - Function of the parotid gland in juvenile recurrent parotitis: a case series. AB - Our aim was to find out how the parotid gland functions in 44 patients with juvenile recurrent parotitis, and to assess the value of measuring the serum amylase activity. Clinical and personal details were recorded, and all patients had their serum amylase activity measured together with sialography during the chronic phase. The function of the gland was classified by sialographic images. The chi square test and Spearman's rank correlation coefficient were used in the statistical analyses. There was a significant association between the degree of glandular function and serum amylase activity (p=0.014). The patients with unilateral and bilateral disease differed significantly in their degree of glandular function (p=0.020), those with bilateral disease having poorer function. There were no significant correlations between other clinical variables and glandular function. Serum amylase activity is an important diagnostic variable in juvenile recurrent parotitis, and poor parotid function reflects the severity of the disease. PMID- 26852268 TI - Harnessing the Prokaryotic Adaptive Immune System as a Eukaryotic Antiviral Defense. AB - Clustered, regularly interspaced, short palindromic repeats - CRISPR-associated (CRISPR-Cas) systems - are sequence-specific RNA-directed endonuclease complexes that bind and cleave nucleic acids. These systems evolved within prokaryotes as adaptive immune defenses to target and degrade nucleic acids derived from bacteriophages and other foreign genetic elements. The antiviral function of these systems has now been exploited to combat eukaryotic viruses throughout the viral life cycle. Here we discuss current advances in CRISPR-Cas9 technology as a eukaryotic antiviral defense. PMID- 26852273 TI - Adsorption-desorption behavior of magnetic amine/Fe3O4 functionalized biopolymer resin towards anionic dyes from wastewater. AB - In this work, a new kind of magnetic amine/Fe3O4 functionalized biopolymer resin (amine/Fe3O4-resin) was prepared and applied to remove various anionic dyes from water. Methyl Orange (MO), Reactive Brilliant Red K-2BP (RBR) and Acid Red 18 (AR) were selected as the typical anionic dye for this research. Meanwhile, amine/Fe3O4-resin was characterized by VSM, XRD, FT-IR, SEM, TEM and XPS. Three anionic dyes removed by amine/Fe3O4-resin were investigated using batch adsorption technique, and the parameters including adsorbent dosage, pH, contact time and temperature were considered. Due to a large number of amine groups and high surface areas, amine/Fe3O4-resin exhibited a remarkably high adsorption capacity for all three dyes, reaching 101.0mg/g, 222.2mg/g and 99.4mg/g for RBR, MO and AR at 25 degrees C, respectively. The pseudo second order model and Langmuir model agreed well with the experimental data, and regeneration experiments indicated its merit of separability and reusability. PMID- 26852272 TI - Effects of sucrose amendment on ammonia assimilation during sewage sludge composting. AB - The aim of this study was to evaluate the laboratory-scale composting of sewage sludge and pumice mixtures that were amended with sucrose. The variation in temperature, pH, NH4(+)-N, ammonia emission, bacterial community, ammonia assimilating bacteria (AAB) populations and enzymatic activity related to ammonia assimilation were detected. The addition of sucrose increased the AAB population by 2.5-3.5 times, reduced ammonia emission by 24.7-31.1% compared with the control treatment, and promoted the growth of Bacillus and Wautersiella. The activities of glutamate dehydrogenase (GDH), glutamate synthase (GS) and glutamine synthetase (GOGAT), were enhanced by the addition of sucrose. GDH made a substantial contribution to ammonia assimilation when the ammonia concentration was high (?1.5g/kg) in the thermophilic phase. The GS/GOGAT cycle played an important role at low ammonia concentrations (?1.1g/kg) in the cooling phase. These results suggested that adding sucrose to sludge compost could promote ammonia assimilation and reduce ammonia emission. PMID- 26852274 TI - Effects of hydraulic retention time and bioflocculant addition on membrane fouling in a sponge-submerged membrane bioreactor. AB - The characteristics of activated sludge and membrane fouling were evaluated in a sponge-submerged membrane bioreactor (SSMBR) at different hydraulic retention times (HRTs) (6.67, 5.33 and 4.00h). At shorter HRT, more obvious membrane fouling was caused by exacerbated cake layer formation and aggravated pore blocking. Activated sludge possessed more extracellular polymeric substances (EPS) due to excessive growth of biomass and lower protein to polysaccharide ratio in soluble microbial products (SMP). The cake layer resistance was aggravated by increased sludge viscosity together with the accumulated EPS and biopolymer clusters (BPC) on membrane surface. However, SMP showed marginal effect on membrane fouling when SSMBRs were operated at all HRTs. The SSMBR with Gemfloc(r) addition at the optimum HRT of 6.67h demonstrated superior sludge characteristics such as larger floc size, less SMP in mixed liquor with higher protein/polysaccharide ratio, less SMP and BPC in cake layer, thereby further preventing membrane fouling. PMID- 26852275 TI - Molecular cloning, SNP detection and association analysis of 5' flanking region of the goat IGF1 gene with prolificacy. AB - The insulin-like growth factor 1 has an important role in reproduction, foetal development and growth. It regulates the secretion of gonadotrophin releasing hormone, stimulates ovarian function and steroidogenesis. The present study was conducted to characterise the 5' flanking region of goat IGF 1 gene, ascertain ovarian expression of the IGF1 gene, detect SNPs and assess the association with prolificacy in the two indigenous goat breeds of South India viz., low prolific Attappady Black and high prolific Malabari. The 5' flanking region of IGF1 gene was PCR amplified, cloned and sequenced from both breeds. Genotyping was performed in 277 goats from the two genetic groups using the PCR-Single Strand Conformational Polymorphism (SSCP) and the expression of the IGF1 gene in the ovary was analysed by quantitative real time PCR. The 5' flanking region of the IGF1 gene was 601 bp long and located at 450 bp upstream of the start codon. Sequence exhibited 97-99% similarity with that of the sheep, cattle and sika deer IGF1 genes. Three genotypes, PP, PQ and QR were observed at this locus with the frequency of 0.62, 0.30 and 0.08, respectively. Sequencing of the representative PCR products from each genotype revealed two SNPs, g.224A>G and g.227C>T. The population was found to be in Hardy-Weinberg disequilibrium at both loci. Statistical results indicated that these loci were associated with litter size (P <= 0.05). However, no significant difference was found in the expression of the IGF1 gene in the ovaries of the two goat breeds. These results suggest the significant influence of the IGF1 gene on prolificacy in goats and identified SNPs would benefit the selection of prolific animals in future breeding programs. PMID- 26852276 TI - Improved survival with combined modality therapy in the modern era for primary mediastinal B-cell lymphoma. AB - Primary mediastinal B-cell lymphoma (PMBCL) is an uncommon lymphoma for which existing data is limited. We utilized the National Cancer Database (NCDB) to evaluate PMBCL and the impact of radiotherapy (RT) on outcomes in the years following FDA approval of rituximab. We queried the NCDB for patients with PMBCL diagnosed from 2006 to 2011 and treated with multiagent chemotherapy. Kaplan Meier overall survival (OS) estimates, univariate (UVA), and multivariate (MVA) Cox proportional hazards regression analyses were performed. Propensity score matched analysis (PSMA) was performed to account for indication bias and mitigate heterogeneity between treatment groups. 465 patients were identified with a median follow-up of 36 months. Median age was 36 years; 43% received RT. 5-year OS for the entire cohort was 87%, and for the no-RT and RT groups, 83% versus 93%, respectively. On UVA, OS was improved with RT (HR 0.34, P = 0.002). On MVA, RT remained significantly associated with improved OS (HR 0.44, P = 0.028) while Medicaid insurance status and increasing stage remained significantly associated with OS decrement. PSMA confirmed the OS benefit associated with RT. This analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT in patients receiving multiagent chemotherapy in the rituximab era. More than half of patients treated in the United States during this time period did not receive RT. In the absence of phase III data to support omission, combined modality therapy with its associated survival benefit should be the benchmark against which other therapies are compared. PMID- 26852277 TI - Pooled population pharmacokinetic model of imipenem in plasma and the lung epithelial lining fluid. AB - AIMS: Several clinical trials have confirmed the therapeutic benefit of imipenem for treatment of lung infections. There is however no knowledge of the penetration of imipenem into the lung epithelial lining fluid (ELF), the site of action relevant for lung infections. Furthermore, although the plasma pharmacokinetics (PK) of imipenem has been widely studied, most studies have been based on selected patient groups. The aim of this analysis was to characterize imipenem plasma PK across populations and to quantify imipenem ELF penetration. METHODS: A population model for imipenem plasma PK was developed using data obtained from healthy volunteers, elderly subjects and subjects with renal impairment, in order to identify predictors for inter-individual variability (IIV) of imipenem PK. Subsequently, a clinical study which measured plasma and ELF concentrations of imipenem was included in order to quantify lung penetration. RESULTS: A two compartmental model best described the plasma PK of imipenem. Creatinine clearance and body weight were included as subject characteristics predictive for IIV on clearance. Typical estimates for clearance, central and peripheral volume, and inter-compartmental clearance were 11.5 l h( 1) , 9.37 l, 6.41 l, 13.7 l h(-1) , respectively (relative standard error (RSE) <8%). The distribution of imipenem into ELF was described using a time independent penetration coefficient of 0.44 (RSE 14%). CONCLUSION: The identified lung penetration coefficient confirms the clinical relevance of imipenem for treatment of lung infections, while the population PK model provided insights into predictors of IIV for imipenem PK and may be of relevance to support dose optimization in various subject groups. PMID- 26852278 TI - Statistical modelling studies examining the dimensional structure of psychopathology experienced by adults with intellectual disabilities: Systematic review. AB - Diagnosing mental ill-health using categorical classification systems has limited validity for clinical practice and research. Dimensions of psychopathology have greater validity than categorical diagnoses in the general population, but dimensional models have not had a significant impact on our understanding of mental ill-health and problem behaviours experienced by adults with intellectual disabilities. This paper systematically reviews the methods and findings from intellectual disabilities studies that use statistical methods to identify dimensions of psychopathology from data collected using structured assessments of psychopathology. The PRISMA framework for systematic review was used to identify studies for inclusion. Study methods were compared to best-practice guidelines on the use of exploratory factor analysis. Data from the 20 studies included suggest that it is possible to use statistical methods to model dimensions of psychopathology experienced by adults with intellectual disabilities. However, none of the studies used methods recommended for the analysis of non-continuous psychopathology data and all 20 studies used statistical methods that produce unstable results that lack reliability. Statistical modelling is a promising methodology to improve our understanding of mental ill-health experienced by adults with intellectual disabilities but future studies should use robust statistical methods to build on the existing evidence base. PMID- 26852279 TI - Relations among motor, social, and cognitive skills in pre-kindergarten children with developmental disabilities. AB - Despite the comorbidity between motor difficulties and certain disabilities, limited research has examined links between early motor, cognitive, and social skills in preschool-aged children with developmental disabilities. The present study examined the relative contributions of gross motor and fine motor skills to the prediction of improvements in children's cognitive and social skills among 2,027 pre-kindergarten children with developmental disabilities, including specific learning disorder, speech/language impairment, intellectual disability, and autism spectrum disorder. Results indicated that for pre-kindergarten children with developmental disabilities, fine motor skills, but not gross motor skills, were predictive of improvements in cognitive and social skills, even after controlling for demographic information and initial skill levels. Moreover, depending on the type of developmental disability, the pattern of prediction of gross motor and fine motor skills to improvements in children's cognitive and social skills differed. Implications are discussed. PMID- 26852282 TI - Attending a concert reduces glucocorticoids, progesterone and the cortisol/DHEA ratio. PMID- 26852280 TI - Urinary and blood cadmium and lead and kidney function: NHANES 2007-2012. AB - BACKGROUND: Cadmium (Cd) and lead (Pb) are widespread environmental contaminants that are known nephrotoxins. However, their nephrotoxic effects at low environmental exposure levels are debated. OBJECTIVE: We examined the association of blood Pb (B-Pb), blood Cd (B-Cd), urinary Pb (U-Pb) and urinary Cd (U-Cd) with estimated glomerular filtration rate (eGFR) and urinary albumin (ALB). METHODS: We used multivariate linear regression to analyze the association between B-Pb, B Cd, U-Pb, and U-Cd with eGFR and ALB in adult participants (>=20 years of age) in NHANES 2007-2012. The dataset was limited to NHANES individuals with both blood and urinary metal measurements. RESULTS: We found a statistically significant inverse association between eGFR and B-Cd and statistically significant positive associations between eGFR and both U-Cd and U-Pb, as well as statistically significant associations between ALB and the 3rd and 4th quartiles of U-Cd. CONCLUSIONS: The inverse association between eGFR and B-Cd, in conjunction with positive associations between eGFR and ALB with U-Cd, suggest that U-Cd measurement at low levels of exposure may result from changes in renal excretion of Cd due to kidney function and protein excretion. However, renal effects such as hyperfiltration from Cd-mediated kidney damage or creatinine-specific Cd effects cannot be excluded with this cross-sectional design. PMID- 26852283 TI - Pilot study investigating the prevalence of oral Human Papilloma Viral (HPV) infection in young adults. PMID- 26852281 TI - Osteocyte Apoptosis Caused by Hindlimb Unloading is Required to Trigger Osteocyte RANKL Production and Subsequent Resorption of Cortical and Trabecular Bone in Mice Femurs. AB - Osteocyte apoptosis is essential to activate bone remodeling in response to fatigue microdamage and estrogen withdrawal, such that apoptosis inhibition in vivo prevents the onset of osteoclastic resorption. Osteocyte apoptosis has also been spatially linked to bone resorption owing to disuse, but whether apoptosis plays a similar controlling role is unclear. We, therefore, 1) evaluated the spatial and temporal effects of disuse from hindlimb unloading (HLU) on osteocyte apoptosis, receptor activator of NF-kappaB ligand (RANKL) expression, bone resorption, and loss in mouse femora, and 2) tested whether osteocyte apoptosis was required to activate osteoclastic activity in cortical and trabecular bone by treating animals subjected to HLU with the pan-caspase apoptosis inhibitor, QVD (quinolyl-valyl-O-methylaspartyl-[-2,6-difluorophenoxy]-methylketone). Immunohistochemistry was used to identify apoptotic and RANKL-producing osteocytes in femoral diaphysis and distal trabecular bone, and uCT was used to determine the extent of trabecular bone loss owing to HLU. In both cortical and trabecular bone, 5 days of HLU increased osteocyte apoptosis significantly (3- and 4-fold, respectively, p < 0.05 versus Ctrl). At day 14, the apoptotic osteocyte number in femoral cortices declined to near control levels but remained elevated in trabeculae (3-fold versus Ctrl, p < 0.05). The number of osteocytes producing RANKL in both bone compartments was also significantly increased at day 5 of HLU (>1.5-fold versus Ctrl, p < 0.05) and further increased by day 14. Increases in osteocyte apoptosis and RANKL production preceded increases in bone resorption at both endocortical and trabecular surfaces. QVD completely inhibited not only the HLU-triggered increases in osteocyte apoptosis but also RANKL production and activation of bone resorption at both sites. Finally, uCT studies revealed that apoptosis inhibition completely prevented the trabecular bone loss caused by HLU. Together these data indicate that osteocyte apoptosis plays a central and controlling role in triggering osteocyte RANKL production and the activation of new resorption leading to bone loss in disuse. (c) 2016 American Society for Bone and Mineral Research. PMID- 26852284 TI - Risk of bias does not differ between full papers and letters reporting dermatological randomized controlled trials. PMID- 26852285 TI - Proteins involved on TGF-beta pathway are up-regulated during the acute phase of experimental Chagas disease. AB - Studies developed by our group in the last years have shown the involvement of TGF-beta in acute and chronic Chagas heart disease, with elevated plasma levels and activated TGF-beta cell signaling pathway as remarkable features of patients in the advanced stages of this disease, when high levels of cardiac fibrosis is present. Imbalance in synthesis and degradation of extracellular matrix components is the basis of pathological fibrosis and TGF-beta is considered as one of the key regulators of this process. In the present study, we investigated the activity of the TGF-beta signaling pathway, including receptors and signaling proteins activation in the heart of animals experimentally infected with Trypanosoma cruzi during the period that mimics the acute phase of Chagas disease. We observed that T. cruzi-infected animals presented increased expression of TGF-beta receptors. Overexpression of receptors was followed by an increased phosphorylation of Smad2/3, p38 and ERK. Furthermore, we correlated these activities with cellular factors involved in the fibrotic process induced by TGF-beta. We observed that the expression of collagen I, fibronectin and CTGF were increased in the heart of infected animals on day 15 post-infection. Correlated with the increased TGF-beta activity in the heart, we found that serum levels of total TGF-beta were significantly higher during acute infection. Taken together, our data suggest that the commitment of the heart associates with increased activity of TGF-beta pathway and expression of its main components. Our results, confirm the importance of this cytokine in the development and maintenance of cardiac damage caused by T. cruzi infection. PMID- 26852286 TI - Could the biological robustness of low level laser therapy (Photobiomodulation) impact its use in the management of mucositis in head and neck cancer patients. AB - Low level laser therapy (LLLT) has been noted to be effective in mitigating the development of oral mucositis among patients being treated with chemoradiation for cancers of the head and neck. To explain the biological basis for this observation we performed a comprehensive literature search. Our investigation identified a substantial number of LLLT-activated pathways that have been strongly associated with negative tumor outcomes including proliferation, invasion, angiogenesis, metastases and cancer-treatment resistance. In light of these findings, we suggest an investigational strategy to assure that LLLT's anti mucositis efficacy is independent of its possible potential to enhance threatening tumor behaviors. Included are appropriate pre-clinical modeling, short- and long-term follow-up of LLLT-treated patients, and the requirement for consistency of LLLT parameters. PMID- 26852287 TI - HPV status is associated with altered PIWI-interacting RNA expression pattern in head and neck cancer. AB - OBJECTIVES: As HPV-induced cases of oral malignancy increase, it is important to understand the molecular differences between HPV positive and negative head and neck squamous cell carcinoma (HNSCC). PIWI-interacting RNAs (piRNAs) are a class of small non-coding RNAs aberrantly expressed in cancer. We analyzed global piRNA expression patterns to define the HNSCC piRNA transcriptome and assess whether HPV infection status associates with changes in piRNA levels. MATERIALS AND METHODS: A total of 498 HNSCC small RNA sequencing libraries were acquired from the Cancer Genomics Hub (cgHUB) Data Repository and a custom sequence analysis pipeline was developed to deduce piRNA expression from raw sequencing data. Expression matrices were aligned to clinicopathological features in order to analyze piRNA expression patterns across different HNSCC groups. The association of a piRNA signature with HPV-positive patient survival was evaluated using a Cox proportional hazard model. RESULTS: Analysis of piRNA levels between HNSCC and non-malignant tissues revealed distinct expression patterns, with 87 piRNAs exclusively expressed in tumor samples. HPV infection status affected the expression of 41 of these piRNAs. Eleven (26.8%) piRNAs were significantly downregulated in HPV16/18 tumors compared to other HPV types. Remarkably, expression of a combination of five-piRNAs in HPV-positive HNSCC tumors was associated with worse overall survival. CONCLUSION: The expression of specific piRNAs is deregulated in HNSCC, and changes with both HPV status and type. Importantly, a five-piRNA signature is able to delineate a subset of HPV-positive HNSCC patients with poor outcome, highlighting the potential utility of piRNAs in patient management. PMID- 26852288 TI - Determination of dimethyl selenide and dimethyl sulphide compounds causing off flavours in bottled mineral waters. AB - Sales of bottled drinking water have shown a large growth during the last two decades due to the general belief that this kind of water is healthier, its flavour is better and its consumption risk is lower than that of tap water. Due to the previous points, consumers are more demanding with bottled mineral water, especially when dealing with its organoleptic properties, like taste and odour. This work studies the compounds that can generate obnoxious smells, and that consumers have described like swampy, rotten eggs, sulphurous, cooked vegetable or cabbage. Closed loop stripping analysis (CLSA) has been used as a pre concentration method for the analysis of off-flavour compounds in water followed by identification and quantification by means of GC-MS. Several bottled water with the aforementioned smells showed the presence of volatile dimethyl selenides and dimethyl sulphides, whose concentrations ranged, respectively, from 4 to 20 ng/L and from 1 to 63 ng/L. The low odour threshold concentrations (OTCs) of both organic selenide and sulphide derivatives prove that several objectionable odours in bottled waters arise from them. Microbial loads inherent to water sources, along with some critical conditions in water processing, could contribute to the formation of these compounds. There are few studies about volatile organic compounds in bottled drinking water and, at the best of our knowledge, this is the first study reporting the presence of dimethyl selenides and dimethyl sulphides causing odour problems in bottled waters. PMID- 26852289 TI - Typical agricultural diffuse herbicide sorption with agricultural waste-derived biochars amended soil of high organic matter content. AB - Biochar application has been identified as the effective soil amendment and the materials to control the diffuse herbicide pollution. The atrazine was selected as the typical diffuse herbicide pollutant as the dominant proportion in applications. The biochar treated from four types of crops biomass were added to soil with high organic matter content. The basic sorption characteristics of biocahrs from corn cob (CC), corn stalk (CS), soybean straw (SS), rice straw (RS) and corn stalk paralyzed with 5% of ammonium dihydrogen phosphate (ACS) were analyzed, along with the comparison of the sorption difference of the raw soil and soil amended with biochars at four levels of ratio (0.5%, 1.0%, 3.0% and 5.0%). It was found that the linear distribution isotherm of raw soil was much effective due to the high organic matter background concentration. The addition of five types of biochars under two kinds of initial atrazine concentration (1 mg/L and 20 mg/L) demonstrated the sorption variances. Results showed the soil amended with RS and CS biochar had the biggest removal rate in four regular biochars and the removal rate of the ACS was the biggest. The sorption coefficient and the normalized sorption coefficient from Freundlich modeling presented the isothermal sorption characteristics of atrazine with soil of high organic matter content. The normalized sorption coefficient increased with the equilibrium concentration decreased in the biochar amended soil, which indicated the sorption performance will be better due to the low atrazine concentration in practice. Results showed that biochar amendment is the effective way to prevent leakage of diffuse herbicide loss. PMID- 26852291 TI - Cardiac structure and function, and ventricular-arterial interaction 11 years following a pregnancy with preeclampsia. AB - Preeclampsia (PE) is associated with acute left ventricular dysfunction. Whether these changes eventually resolve remains unclear. This study assessed left and right ventricular structure and function, and ventricular-arterial interaction in 15 women 11 years after a pregnancy with PE and 16 matched control subjects with a normal pregnancy. We found normal left and right ventricular dimensions, systolic function, and global left ventricular strain, with no differences between the groups. In addition, indices of diastolic function, left and right atrial size, and amino-terminal pro-brain natriuretic peptide were normal and did not differ between the groups. Women with a previous PE had impaired night/day ratios for systolic and diastolic ambulatory blood pressure. However, indices of aortic stiffness or ventricular-arterial coupling did not differ between the groups. In conclusion, we could not demonstrate remaining alterations in systolic or diastolic left or right ventricular function, or in ventricular-arterial interaction in women 11 years after PE. PMID- 26852290 TI - Physician-pharmacist collaboration versus usual care for treatment-resistant hypertension. AB - Team-based care has been recommended for patients with treatment-resistant hypertension (TRH), but its efficacy in this setting is unknown. We compared a physician-pharmacist collaborative model (PPCM) to usual care in patients with TRH participating in the Collaboration Among Pharmacists and Physicians To Improve Outcomes Now study. At baseline, 169 patients (27% of Collaboration Among Pharmacists and Physicians To Improve Outcomes Now patients) had TRH: 111 received the PPCM intervention and 58 received usual care. Baseline characteristics were similar between treatment arms. After 9 months, adjusted mean systolic blood pressure was reduced by 7 mm Hg more with PPCM intervention than usual care (P = .036). Blood pressure control was 34.2% with PPCM versus 25.9% with usual care (adjusted odds ratio, 1.92; 95% confidence interval, 0.33 11.2). These findings suggest that team-based care in the primary care setting may be effective for TRH. Additional research is needed regarding the long-term impact of these models and to identify patients most likely to benefit from team based interventions. PMID- 26852292 TI - Clinical evidence on titanium-zirconium dental implants: a systematic review and meta-analysis. AB - The use of titanium implants is well documented and they have high survival and success rates. However, when used as reduced-diameter implants, the risk of fracture is increased. Narrow diameter implants (NDIs) of titanium-zirconium (Ti Zr) alloy have recently been developed (Roxolid; Institut Straumann AG). Ti-Zr alloys (two highly biocompatible materials) demonstrate higher tensile strength than commercially pure titanium. The aim of this systematic review was to summarize the existing clinical evidence on dental NDIs made from Ti-Zr. A systematic literature search was performed using the Medline database to find relevant articles on clinical studies published in the English language up to December 2014. Nine clinical studies using Ti-Zr implants were identified. Overall, 607 patients received 922 implants. The mean marginal bone loss was 0.36+/-0.06mm after 1 year and 0.41+/-0.09mm after 2 years. The follow-up period ranged from 3 to 36 months. Mean survival and success rates were 98.4% and 97.8% at 1 year after implant placement and 97.7% and 97.3% at 2 years. Narrow diameter Ti-Zr dental implants show survival and success rates comparable to regular diameter titanium implants (>95%) in the short term. Long-term follow-up clinical data are needed to confirm the excellent clinical performance of these implants. PMID- 26852293 TI - Age effects on the control of dynamic balance during step adjustments under temporal constraints. AB - This study investigated the age effects on the control of dynamic balance during step adjustments under temporal constraints. Fifteen young adults and 14 older adults avoided a virtual white planar obstacle by lengthening or shortening their steps under free or constrained conditions. In the anterior-posterior direction, older adults demonstrated significantly decreased center of mass velocity at the swing foot contact under temporal constraints. Additionally, the distances between the 'extrapolated center of mass' position and base of support at the swing foot contact were greater in older adults than young adults. In the mediolateral direction, center of mass displacement was significantly increased in older adults compared with young adults. Consequently, older adults showed a significantly increased step width at the swing foot contact in the constraint condition. Overall, these data suggest that older adults demonstrate a conservative strategy to maintain anterior-posterior stability. By contrast, although older adults are able to modulate their step width to maintain mediolateral dynamic balance, age-related changes in mediolateral balance control under temporal constraints may increase the risk of falls in the lateral direction during obstacle negotiation. PMID- 26852295 TI - On endocytosis of foreign ferritin and occurrence of phagolysosomes in fish heart endothelial cells. AB - In the present study the ultrastructure and function of the endothelial cells enveloping the muscle trabeculae in heart in two teleosts, platyfish and firemouth cichlid, are described and discussed. These cells displayed a structure making them able to take up large amounts of foreign ferritin particles from the blood stream. The ferritin particles were assembled into huge phagolysosomes. Large amounts of Prussian blue were precipitated throughout these lysosomes when treated with acid ferrohexacyanide solution. The occurrence of Prussian blue precipitations in the control heart endothelial cells after Schmorl's solution, suggests that these cells normally contain undigestible material, a finding which strengthens the view that this tissue is involved in blood clearance in the present species. In conclusion, these heart endothelial cells seem able to perform a very efficient blood clearance of scavenger and foreign macromolecules and particles in the present species. PMID- 26852294 TI - Elastase modifies bleomycin-induced pulmonary fibrosis in mice. AB - Pulmonary fibrosis (PF) is characterized by excessive accumulation of collagen in the lungs. Emphysema is characterized by loss of the extracellular matrix (ECM) and alveolar enlargement. We studied the co-participation of elastase-induced mild emphysema in bleomycin-induced PF in mice by analyzing oxidative stress, inflammation and lung histology. C57BL/6 mice were divided into four groups: control; bleomycin (0.1U/mouse); elastase (using porcine pancreatic elastase (PPE)+bleomycin (3U/mouse 14 days before 0.1U/mouse of bleomycin; PPE+B); elastase (3U/mouse). Mice were humanely sacrificed 7, 14 and 21 days after treatment with bleomycin or vehicle. PF was observed 14 days and 21 days after bleomycin treatment but was observed after 14 days only in the PPE+B group. In the PPE+B group at 21 days, we observed many alveoli and alveolar septa with few PF areas. We also observed marked and progressive increases of collagens 7, 14 and 21 days after bleomycin treatment whereas, in the PPE+B group, collagen deposition was observed only at 14 days. There was a reduction in activities of the antioxidant enzymes superoxide dismutase (p<0.05), catalase (p<0.01) and glutathione peroxidase (p<0.01) parallel with an increase in nitrite (p<0.01) 21 days after bleomycin treatment compared with the control group. These endpoints were also reduced (p<0.05, p<0.05 and p<0.01, respectively) and increased (p<0.01) in the PPE+B group at 21 days compared with the control group. Interleukin (IL)-1beta expression was upregulated (p<0.01) whereas IL-6 was downregulated (p<0.05) in the PPE+B group at 21 days compared with the control group. PF and emphysema did not coexist in our model of lung disease and despite increased levels of oxidative stress and inflammatory markers after combined stimulus (elastase and bleomycin) overall histology was improved to that of the nearest control group. PMID- 26852296 TI - Facile endothelial cell micropatterning induced by reactive oxygen species on polydimethylsiloxane substrates. AB - Sophisticated cell pattern provides unique cellular assay platform for studying cell to cell interaction, cellular differentiation and signaling, high-throughput cell response to chemicals. In this study, we demonstrated reactive oxygen species (ROS) mediated endothelial cell micropatterning on a polydimethylsiloxane (PDMS) substrate. The exposure of UV/O radiation led to the formation of ROS on the surface of PDMS, which could selectively prevent adhesion of endothelial cells. The degree of ROS amount was monitored according to the UV/O irradiation time, and at least 36 MUM of ROS resulted in the precise cellular micropattern on the PDMS. The presence of ROS affected not only cellular detachment from the substrate, but also endothelial cell morphology such as cell spreading area, confluence, nuclear area and nuclear inverse aspect ratio. In addition, we could observe that the actin cytoskeleton of cells was also constricted due to ROS, thereby minimizing the focal adhesion area of vinculin. Compared with previously reported methods which use chemical treatment or nano/microstructure on the substrate, the proposed methodology is quite simple, accurate, and harmless to the patterned endothelial cells. PMID- 26852297 TI - Periodontal therapy as adjunctive treatment for gastric Helicobacter pylori infection. AB - BACKGROUND: Helicobacter pylori is estimated to affect about half the world's population and is considered as the main cause of chronic gastritis and peptic ulcer disease. Eradication of H. pylori infection accelerates ulcer healing and prevents relapse, reducing incidence of H. pylori-related gastric diseases. Numerous studies have provided evidence that the oral cavity could be a potential reservoir for H. pylori. The presence of oralH. pylori might affect the efficiency of eradication therapy and act as a causal force for its recurrence. Conversely, other investigators have indicated that the colonization and growth of H. pylori differs between the oral cavity and the stomach. Considering the open debate on the topic, it's necessary to clarify whether periodontal therapy is an effective adjunctive treatment for gastric H. pylori infection. OBJECTIVES: To assess the effects of periodontal therapy plus eradication therapy versus eradication therapy alone for gastric H. pylori infection. The secondary objective is to compare the non-recurrence rate at long-term follow up in different treatment groups. SEARCH METHODS: We identified randomized controlled trials (RCTs) by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, Issue 8), MEDLINE (1946 to August 2015), EMBASE (1980 to August 2015), and the Chinese Biomedical Database (1978 to August 2015). We also searched both ClinicalTrials.gov and the WHO ICTRP portal in October 2015. We handsearched the reference lists of included studies to identify relevant trials. SELECTION CRITERIA: RCTs comparing periodontal therapy plus eradication treatment with eradication treatment alone, regardless of language of publication. DATA COLLECTION AND ANALYSIS: Two reviewers selected the trials that met the inclusion criteria and extracted the details of each study independently. The data were pooled using both fixed-effect and random-effects models and results calculated as odds ratios (OR) with their 95% confidence intervals (CIs) based on an intention-to-treat analysis. However, because there was little difference in the results from these two models, we only reported the results from the fixed-effect model. MAIN RESULTS: We included seven small RCTs involving 691 participants aged 17 to 78 years in our meta analyses. The primary result showed that periodontal therapy combined with H. pylori eradication treatment increased the eradication rate of gastric H. pylori compared with eradication treatment alone (OR 2.15; 95% CI 1.47 to 3.14; P < 0.0001) in people with H. pylori infection. In addition, periodontal therapy also had benefits on long-term gastric H. pylori eradication. After eradication of H. pylori, the non-recurrence rate of gastric H. pylori infection increased in participants treated with periodontal therapy compared with those who received eradication therapy alone (OR 3.60; 95% CI 2.11 to 6.15; P < 0.00001). According to the GRADE approach, the overall quality of the evidence was 'moderate' for eradication rate of gastric H.pylori and 'low' for non-recurrence rate of gastric H. pylori. AUTHORS' CONCLUSIONS: Overall, periodontal therapy could increase the efficiency of H. pylori eradication and the non-recurrence rate of gastricH. pylori. In view of the limited number and quality of included studies, it will be necessary to conduct more well-designed, multicenter, and large-scale RCTs to determine the effects of periodontal therapy in eradicating gastric H. pylori and suppressing the recurrence of this bacterium in the stomach. PMID- 26852298 TI - Congenital H-type tracheoesophageal fistula: a national multicenter study. AB - BACKGROUND: Congenital H-type tracheoesophageal fistula (TEF) is very rare and represents <5 % of all congenital tracheoesophageal malformations. This is a national, multicenter review of our experience with isolated H-type TEF outlining clinical presentation, methods of diagnosis, associated anomalies, treatment and outcome PATIENTS AND METHODS: The medical records of all patients with the diagnosis of congenital H-type TEF treated at four pediatric surgery units in Saudi Arabia were retrospectively reviewed for: age at diagnosis, sex, presenting symptoms, associated anomalies, method of diagnosis, treatment and outcome. RESULTS: During the study period (January 1998-December 2013), 435 infants and children with the diagnosis of esophageal atresia with or without TEF were treated. Among these, 23 (5.3 %) had isolated TEF. There were 11 males and 12 females. Their age at presentation ranged from 5 days to 3 years and 7 months but the majority (90 %) were diagnosed during their first year of life. Their clinical presentation included: chocking and coughing during feeds in 12 (52.2 %), recurrent chest infection in 16 (69.6 %) and cyanosis in 10 (43.5 %). One presented with abdominal distension also. The diagnosis was made using esophagogram. In 11 (47.8 %), a single study confirmed the diagnosis, 8 (34.8 %) required two studies while 4 (17.4 %) required three studies. Nineteen (82.6 %) had preoperative bronchoscopy and in 13 (56.5 %), a catheter was used to cannulate the fistula. All were operated through a right cervical incision except one who underwent thoracoscopic ligation and division of the fistula. In one, the fistula was only transfixed and tied without being divided. This patient developed a recurrent fistula. Two patients developed postoperative stridor secondary to recurrent laryngeal nerve palsy. In both of them, there was complete recovery. CONCLUSIONS: H-type TEF is very rare and commonly presents with recurrent chest infection, chocking and coughing during feeds and cyanosis. Physicians caring for these patients should be aware of this and a high index of suspicion is of paramount importance to avoid delay in diagnosis with its associated morbidity. A contrast esophagogram is valuable in confirming the diagnosis. The study however may need to be repeated. Preoperative bronchoscopy is valuable to localize and cannulate the fistula for easier access during surgery. Surgical repair is the treatment of choice and this should be performed through a right cervical incision or thoracotomy for low fistulae. Thoracoscopic ligation and division of a low H-type fistula is an alternative and less invasive approach when compared to thoracotomy. PMID- 26852299 TI - 'Right for publication': another strategy to promote publications by novice authors. PMID- 26852300 TI - [French translation of "An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction" published in Int Urogynecol J 2010;21(1):5-26]. AB - INTRODUCTION AND HYPOTHESIS: Given its increasing complexity, the terminology for female pelvic floor disorders needs to be updated in addition to existing terminology of the lower urinary tract. To do this, it seems preferable to adopt a female-specific approach and build on a consensus based on clinical practice. METHODOLOGY: This paper summarizes the work of the standardization and terminology committees of two international scientific societies, namely the International Urogynecological Association (IUGA) and the International Continence Society (ICS). These committees were assisted by many external expert referees. A ranking into relevant major clinical categories and sub-categories was developed in order to allocate an alphanumeric code to each definition. An extensive process of 15 internal and external reviews was set up to study each definition in detail, with decisions taken collectively (consensus). RESULTS: Terminology was developed for female pelvic floor disorders, bringing together more than 250 definitions. It is clinically based and the six most common diagnoses are defined. The emphasis was placed on clarity and user-friendliness to make this terminology accessible to practitioners and trainees in all the specialties involved in female pelvic floor disorders. Imaging investigations (ultrasound, radiology, MRI) exclusively for women have been added to the text, relevant figures have also been included to complete the text and help clarify the meaning. Regular reviews are planned and are also required to keep the document up-to-date and as widely acceptable as possible. CONCLUSIONS: The work conducted led to the development of a consensual terminology of female pelvic floor disorders. This document has been designed to provide substantial assistance in clinical practice and research. LEVEL OF EVIDENCE: 4. PMID- 26852301 TI - Four complement factor H gene polymorphisms in association with AMD: A meta analysis. AB - AIM: To investigate the possible association between CFH gene polymorphisms 543G>A (rs1410996), A473A (rs2274700), -257C>T (rs3753394), IVS15 (rs1329428) and AMD risk. METHODS: We searched the published literature in the Medline and Scopus from inception to May 2015. A meta-analysis was performed by the programs RevMan 5.1 and Stata 12.0, and the Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated in fixed or random effect model based on heterogeneity test among studies. RESULTS: Nineteen studies with a total of 10,676 subjects were included in the present meta-analysis. A statistical significant association was observed between AMD risk and CFH -543G>A polymorphism with OR of 1.77 (95% CI, 1.47-2.12), 2.24 (95% CI, 1.71-2.94), 0.49 (95% CI, 0.38-0.62) and 0.25 (95% CI, 0.18-0.37) in additive, dominant, recessive and codominant models, respectively. Similar results were obtained in polymorphisms A473A, -257C>T, IVS15. Furthermore, stratified analysis for ethnicity showed a significantly strong association between -543G>A, A473A polymorphisms and AMD risk. CONCLUSION: The present meta-analysis suggested that CFH -543G>A, A473A, -257C>T, and IVS15 polymorphisms might be moderately associated with AMD risk. This conclusion warrants confirmation by further studies. PMID- 26852302 TI - Transcatheter device closure of pseudoaneurysms of the left ventricular wall: An emerging therapeutic option. AB - Left ventricular pseudoaneurysm is a rare but serious complication of acute myocardial infarction and cardiac surgery. While surgical intervention is the conventional therapeutic option, transcatheter closure can be considered in selected patients with suitable morphology of the pseudoaneurysm. We report a case of successful transcatheter closure of a left ventricular pseudoaneurysm orifice and isolation of the sac using an Amplatzer septal occluder. PMID- 26852303 TI - Coronary optical coherence tomography: A practical overview of current clinical applications. AB - Coronary optical coherence tomography has emerged as the most powerful in-vivo imaging modality to evaluate vessel structure in detail. It is a useful research tool that provides insights into the pathogenesis of coronary artery disease. This technology has an important clinical role that is still being developed. We review the evidence on the wide spectrum of potential clinical applications for coronary optical coherence tomography, which encompass the successive stages in coronary artery disease management: accurate lesion characterization and quantification of stenosis, guidance for the decision to perform percutaneous coronary intervention and subsequent planning, and evaluation of immediate and long-term results following intervention. PMID- 26852304 TI - Translation and cultural adaptation of the Hill-Bone Compliance to High Blood Pressure Therapy Scale to Portuguese. AB - INTRODUCTION: Hypertension is an extremely prevalent disease worldwide and hypertension control rates remain low. Lack of adherence contributes to poor control and to cardiovascular events. No questionnaire in Portuguese is readily available for the assessment of adherence to antihypertensive drugs. We aimed to perform a translation and cultural adaptation to Portuguese of the Hill-Bone Compliance to High Blood Pressure Therapy Scale, a validated instrument to measure adherence in hypertensive patients. METHODS: A formal process was employed, consisting of a forward translation by two independent translators and a back translation by a third translator. Discrepancies were resolved after each step. Hypertensive patients were involved to identify and resolve phrasing and wording difficulties and misunderstandings. RESULTS: The forward and back translation did not produce significant discrepancies. However, important issues were identified when the questionnaire was presented to patients, which led to changes in the wording of the questions and in the format of the questionnaire. CONCLUSION: Questionnaires are important instruments to assess adherence to therapy, particularly in hypertension. A formal translation and cultural adaptation process ensures that the new version maintains the same concepts as the original. After translation, several changes were necessary to ensure that the questionnaire was understandable by elderly, low literacy patients, such as the majority of hypertensive patients. We propose a Portuguese version of the Hill-Bone Compliance Scale, which will require validation in further studies. PMID- 26852306 TI - Complete aortic coarctation. PMID- 26852305 TI - Three-dimensional transesophageal echocardiography in the diagnosis of biological prosthetic valve thrombosis (and its resolution). PMID- 26852307 TI - Percutaneous closure of a large ascending aortic pseudoaneurysm. AB - Pseudoaneurysm of the ascending aorta is a rare complication, usually after thoracic surgery or trauma. Since surgical repair is associated with very high morbidity and mortality, percutaneous closure has been described as an alternative. In this regard, we present a case in which a symptomatic large pseudoaneurysm of the ascending aorta was treated percutaneously due to the high surgical risk. Despite the technical difficulties, this procedure had a good final result followed by clinical success. PMID- 26852308 TI - Multiple left ventricular aneurysms in a young female. AB - Multiple left ventricular aneurysms (LVAs) are rare, especially in a young female. A 29-year-old woman presented vague symptoms. Multiple LVAs were revealed and confirmed on different imaging modalities, including chest radiography, echocardiography, contrast ventriculography and cardiac magnetic resonance imaging. Detailed work-up for probable etiologies including ischemic, infectious, inflammatory and autoimmune causes was negative. In the absence of angina, decompensated congestive heart failure, arrhythmias and embolism, the patient was managed conservatively, with excellent mid-term outcome. PMID- 26852309 TI - Percutaneous closure of a coronary fistula with single Amplatzer Vascular Plug II in a five-month-old female: The youngest case report. AB - Coronary artery fistula (CAF) is a rare clinical abnormality characterized by a connection between one or more coronary arteries and an adjacent cardiac chamber or vascular structure. Although CAF complications are more common in older children over time, there is still no consensus in terms of treatment indications in children with asymptomatic fistula. We describe an asymptomatic infant diagnosed with a severely dilated right coronary artery and a coronary-cameral fistula treated successfully by transcatheter device closure. The Amplatzer Vascular Plug II appears to be safe, effective and relatively easy to use for CAF closure in infants. PMID- 26852310 TI - Left atrial ejection force correlates with left atrial strain and volume-based functional properties as assessed by three-dimensional speckle tracking echocardiography (from the MAGYAR-Healthy Study). AB - INTRODUCTION AND OBJECTIVE: Three-dimensional (3D) speckle tracking echocardiography (3DSTE) is a novel method for assessment of left atrial (LA) volumes and function without geometrical assumptions. 3DSTE allows detailed assessment of LA features including volume measurements, strain assessments and calculation of LA ejection force (LAEF). LA strain and volume-based functional parameters originate from the same 3D dataset, but assessment of LAEF requires more data including measurement of mitral annular dimensions and Doppler-derived inflow velocities. The present study was designed to find correlations between LAEF and 3DSTE-derived LA volume-based functional properties and strain parameters in healthy subjects. METHODS: The study population comprised 34 randomly selected healthy subjects (age 36.1+/-11.2 years, 15 men) in sinus rhythm, all of whom had undergone standard two-dimensional transthoracic Doppler echocardiographic study extended with 3DSTE. RESULTS: Mitral annulus diameter based LAEF correlated with global LA peak circumferential (r=0.39, p=0.02), longitudinal (r=0.32, p=0.05) and area (r=0.43, p=0.01) strain, total atrial stroke volume (r=0.30, p=0.05) and total atrial emptying fraction (r=0.31, p=0.05) characterizing (systolic) LA reservoir function and global LA 3D strain at atrial contraction (r=-0.44, p=0.01) and active atrial emptying fraction (r=0.36, p=0.04) characterizing (diastolic) LA contraction function (booster pump phase). CONCLUSIONS: Complex LA functional assessment can be provided by 3DSTE, including calculation of LAEF and volume-based and strain functional properties, with significant correlations between these parameters. PMID- 26852311 TI - Comparison Between Different Flavored Olive Oil Production Techniques: Healthy Value and Process Efficiency. AB - Three different flavoring methods of olive oil were tested employing two different herbs, thyme and oregano. The traditional method consist in the infusion of herbs into the oil. A second scarcely diffused method is based on the addition of herbs to the crushed olives before the malaxation step during the extraction process. The third innovative method is the implementation of the ultrasound before the olive paste malaxation. The objective of the study is to verify the effect of the treatments on the quality of the product, assessed by means of the chemical characteristics, the phenol composition and the radical scavenging activity of the resulting oils. The less favorable method was the addition of herbs directly to the oil. A positive effect was achieved by the addition of herbs to the olive paste and other advantages were attained by the employment of ultrasound. These last two methods allow to produce oils "ready to sell", instead the infused oils need to be filtered. Moreover, the flavoring methods applied during the extraction process determine a significant increment of phenolic content and radical scavenging activity of olive oils. The increments were higher when oregano is used instead of thyme. Ultrasound inhibited the olive polyphenoloxidase, the endogenous enzyme responsible for olive oil phenol oxidation. This treatment of olive paste mixed with herbs before malaxation was revealed as the most favorable method due to the best efficiency, reduced time consumption and minor labor, enhancing the product quality of flavored olive oil. PMID- 26852312 TI - Coastal fog during summer drought improves the water status of sapling trees more than adult trees in a California pine forest. AB - Fog water inputs can offset seasonal drought in the Mediterranean climate of coastal California and may be critical to the persistence of many endemic plant species. The ability to predict plant species response to potential changes in the fog regime hinges on understanding the ways that fog can impact plant physiological function across life stages. Our study uses a direct metric of water status, namely plant water potential, to understand differential responses of adult versus sapling trees to seasonal drought and fog water inputs. We place these measurements within a water balance framework that incorporates the varying climatic and soil property impacts on water budgets and deficit. We conducted our study at a coastal and an inland site within the largest stand of the regionally endemic bishop pine (Pinus muricata D. Don) on Santa Cruz Island. Our results show conclusively that summer drought negatively affects the water status of sapling more than adult trees and that sapling trees are also more responsive to changes in shallow soil moisture inputs from fog water deposition. Moreover, between the beginning and end of a large, late-season fog drip event, water status increased more for saplings than for adults. Relative to non-foggy conditions, we found that fog water reduces modeled peak water deficit by 80 and 70 % at the inland and coastal sites, respectively. Results from our study inform mechanistically based predictions of how population dynamics of this and other coastal species may be affected by a warmer, drier, and potentially less foggy future. PMID- 26852313 TI - Recently diagnosed rheumatoid arthritis patients benefit from a treat-to-target strategy: results from the DREAM registry. AB - Despite considerable evidence on the efficacy and safety of early aggressive treat-to-target (T2T) strategies in early rheumatoid arthritis (RA), a proportion of patients still fail to reach remission. The goal of this study is to examine remission rates and predictors of remission in a real life T2T cohort of consecutive patients with a recent diagnosis of RA. Baseline demographics, clinical, laboratory and patient-reported variables and 1-year follow-up disease activity data were used from patients with early RA included in the DREAM remission induction cohort II study. Survival analyses and simple and multivariable logistic regression analyses were used to examine remission rates and significant predictors of achieving remission. A total of 137 recently diagnosed consecutive RA patients were available for this study. During the first year after inclusion, DAS28 remission was achieved at least once in 77.2 % of the patients and the median time to first remission was 17 weeks. None of the examined baseline variables were robustly associated with achieving remission within 1 year and in the multivariable analysis only lower ESR (p = 0.005) remained significantly associated with achieving fast remission within 17 weeks. During the first year of their disease a high proportion of recently diagnosed RA patient achieved remission, with only a small percentage of patients needing bDMARD therapy. Combined with the absence of baseline predictors of remission, this suggests that clinicians in daily clinical practice may focus on DAS28 scores only, without needing to take other patients characteristics into account. PMID- 26852314 TI - Prevalence of musculoskeletal disorders and rheumatic diseases in the indigenous Qom population of Rosario, Argentina. AB - This study aimed to estimate the prevalence of musculoskeletal disorders and rheumatic diseases among the indigenous Qom (Toba) population in the city of Rosario, Santa Fe, Argentina. An analytical cross-sectional study using methodology of the Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) was performed. Subjects >=18 years of age were interviewed by advanced students of medicine and nursing, bilingual translator-facilitators, and coordinators. Individuals with musculoskeletal pain (positive cases) were evaluated sequentially for 7 days by internists and rheumatologists for diagnosis and treatment. The study included 1656 individuals (77 % of the census population). Of these, 1020 (61.5 %) were female, with mean age of 35.3 (SD 13.9) years, and 1028 (62.0 %) were bilingual. The public health care system covers 87.1 % of the population. Musculoskeletal pain in the previous 7 days and/or at some time during their life was present in 890 subjects (53.7 %). Of those with pain in the last 7 days, 302 (64.1 %) subjects had an Health Assessment Questionnaire Disability Index (HAQ-DI) score >=0.8. The most frequent pain sites were lumbar spine (19.3 %), knees (13.0 %), and hands (12.0 %). The prevalence of rheumatic diseases was as follows: mechanical back pain (20.1 %), rheumatic regional pain syndrome (2.9 %), osteoarthritis (4.0 %) rheumatoid arthritis (2.4 %), inflammatory back pain (0.2 %), systemic sclerosis (0.1 %), Sjogren syndrome (0.1 %), fibromyalgia (0.1 %), mixed connective tissue disease (0.06 %), and systemic lupus erythematosus (0.06 %). The prevalence of musculoskeletal disorders was 53.7 % and rheumatic diseases 29.6 %. Rheumatoid arthritis prevalence was 2.4 % using COPCORD methodology, one of the highest reported at present. PMID- 26852315 TI - Vitamin A improve Th17 and Treg regulation in systemic lupus erythematosus. AB - The aim of this study was to determine the role of vitamin A in modulating T helper 17 (Th17) and regulatory T cell (Treg) balance in systemic lupus erythematosus (SLE) patients. Sixty-two female SLE patients and sixty-two female controls were measured for vitamin A levels from serum by enzyme-linked immunosorbent assay (ELISA) and percentages of Th17 and Treg from peripheral blood mononuclear cells (PBMC) by flow cytometry. We also performed an in vitro study to evaluate the effects of retinoic acid treatment (0, 0.1, 0.2, and 0.3 MUg/ml) in modulating Th17/Treg balance in CD4(+) T cell culture from hypovitaminosis A SLE patients. Th17 and Treg percentages from cell cultures were measured by flow cytometry. Vitamin A levels in the SLE patients were lower compared to those in the healthy control (46.9 +/- 43.4 vs. 75.6 +/- 73.1 ng/ml, p = 0.015). Vitamin A levels also had a negative correlation to Th17 percentages in the SLE patients (p = 0.000, R = -0.642). Th17 percentages in the hypovitaminosis A SLE patients were higher compared to those SLE patients with normal vitamin A levels (10.9 +/- 5.3 vs. 2.9 +/- 2.2 %, p = 0.000). Treatment of 0.3 MUg/ml of retinoic acid could increase Treg differentiation (33.9 +/- 1.6 vs. 21.8 +/- 1.1 %, p = 0.000) and decrease Th17 differentiation (27.2 +/- 2.5 vs. 37.4 +/- 1.3 %, p = 0.000). In conclusion, vitamin A has important roles in modulating Th17/Treg balance in the SLE patients shown by the significant decrease of vitamin A levels in the SLE patients which negatively correlate with Th17 population, and treatment of retinoic acid could decrease Th17 and increase Treg percentages in CD4(+) T cells cultures. PMID- 26852316 TI - Indirect comparisons of the efficacy of subsequent biological agents in patients with psoriatic arthritis with an inadequate response to tumor necrosis factor inhibitors: a meta-analysis. AB - Significant portion of patients with psoriatic arthritis (PsA) could not tolerate or do not have a satisfactory response to either non-steroidal anti-inflammatory drugs (NSAIDs), non-biologic disease-modifying anti-rheumatic drugs (DMARDs), or even TNF inhibitors. Non-TNF inhibitor biologic agents have emerged as second line therapy in such situation. However, the comparative efficacy of these agents remains unknown as head-to-head randomized controlled trials (RCTs) are not available. RCTs examining the efficacy of non-TNF inhibitor biologic agents in patients with PsA who experienced inadequate response or intolerance of TNF inhibitors were identified. If more than one RCT was available for a given biologic agent, the pooled odds ratio (OR) and 95 % confidence interval (CI) of achieving 20 % improvement according to American College of Rheumatology criteria (ACR20) response across trials were calculated. The pooled OR for each biologic agent was then compared using the indirect comparison technique. Five RCTs of four non-TNF inhibitor biologic agents, including abatacept, secukinumab, ustekinumab, and apremilast, with 675 participants were identified and included in the data analyses. We found no significant difference in any comparisons, with the p values ranging from 0.14 to 0.98. Our study demonstrates that the likelihood of achieving the ACR20 response in patients with TNF inhibitor experience is not significantly different between the four non-TNF biologic agents. However, the interpretation of this analysis is limited by the small sample sizes. Head-to-head comparisons are still required to confirm the comparative efficacy. PMID- 26852318 TI - Ophthalmology in ancient Greece and Rome. PMID- 26852317 TI - Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement. AB - Several classification schemes have been developed for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with actual debate focusing on their clinical and prognostic performance. Sixty-two patients with renal biopsy-proven AAV from a single center in Mexico City diagnosed between 2004 and 2013 were analyzed and classified under clinical (granulomatosis with polyangiitis [GPA], microscopic polyangiitis [MPA], renal limited vasculitis [RLV]), serological (proteinase 3 anti-neutrophil cytoplasmic antibodies [PR3 ANCA], myeloperoxidase anti-neutrophil cytoplasmic antibodies [MPO-ANCA], ANCA negative), and histopathological (focal, crescenteric, mixed-type, sclerosing) categories. Clinical presentation parameters were compared at baseline between classification groups, and the predictive value of different classification categories for disease and renal remission, relapse, renal, and patient survival was analyzed. Serological classification predicted relapse rate (PR3-ANCA hazard ratio for relapse 2.93, 1.20-7.17, p = 0.019). There were no differences in disease or renal remission, renal, or patient survival between clinical and serological categories. Histopathological classification predicted response to therapy, with a poorer renal remission rate for sclerosing group and those with less than 25 % normal glomeruli; in addition, it adequately delimited 24-month glomerular filtration rate (eGFR) evolution, but it did not predict renal nor patient survival. On multivariate models, renal replacement therapy (RRT) requirement (HR 8.07, CI 1.75-37.4, p = 0.008) and proteinuria (HR 1.49, CI 1.03 2.14, p = 0.034) at presentation predicted renal survival, while age (HR 1.10, CI 1.01-1.21, p = 0.041) and infective events during the induction phase (HR 4.72, 1.01-22.1, p = 0.049) negatively influenced patient survival. At present, ANCA based serological classification may predict AAV relapses, but neither clinical nor serological categories predict renal or patient survival. Age, renal function and proteinuria at presentation, histopathology, and infectious complications constitute the main outcome predictors and should be considered for individualized management. PMID- 26852319 TI - Development of The Johns Hopkins University School of Nursing Adult/Geriatric Primary Care Nurse Practitioner Program in HIV Prevention, Treatment, and Care. AB - In response to the call to create an AIDS Education and Training Center for Nurse Practitioner Education by the Health Resources and Services Administration, The Johns Hopkins University School of Nursing embarked on a transformative curriculum overhaul to integrate HIV prevention, treatment, and care into the Adult/Geriatric Nurse Practitioner Program. A six-step process outlined in the Curriculum Development for Medical Education was followed. A pilot cohort of Adult/Geriatric Nurse Practitioner students were enrolled, including 50% primary care setting and 50% HIV-focused primary care through a 12-month HIV continuity clinic experience. Through this pilot, substantive changes to the program were adopted. Programmatic outcomes were not compromised with the modification in clinical hours. The model of a 12-month HIV continuity clinical experience reduced the number of required preceptors. This model has important implications for the HIV workforce by demonstrating successful integration of HIV and primary care training for nurse practitioners. PMID- 26852320 TI - Geometry of inferior endplates of the cervical spine. AB - OBJECTIVES: Device subsidence is a well-known complication following cervical disc arthroplasty. Its occurrence has been closely tied with the endplate-implant contact interface. But current literature on the geometry of cervical endplate is very scarce. The aim of this anatomical investigation was to analyze geometry of inferior endplates of the cervical vertebrae, thereby identifying the common endplate shape patterns and providing morphological reference values consummating the design of the implant. PATIENTS AND METHODS: Reformatted CT scans of 85 individuals were analyzed and endplate concave depth, endplate concave apex location, sagittal diameter of endplate, coronal concave angle, as well as transverse diameter of endplate were measured in mid-sagittal plane and specified coronal plane. According to the endplate concave apex location, the inferior endplates in mid-sagittal plane were classified into 3 types: type I with posteriorly positioned apex, type II with middle situated concave apex and type III with anteriorly positioned apex. Moreover, the inferior endplates in specified coronal plane were also classified into three types: concave, flat and irregular. RESULTS: Based on visual assessment, for the mid-sagittal plane, type I endplate accounted for 26.9% of all the 510 endplates of 85 individuals, while the proportion of type II and type III endplates were 53.9 and 19.2% respectively. For the specified coronal plane, 68.6% of all the 510 endplates were evaluated as concave, 26.9% as flat and the remaining 4.5% as irregular. Among all measured segments, C3 had the largest endplate concave depth values in mid-sagittal plane, while C7 the least; C5 and C6 had the largest sagittal endplate diameter values, while C2 the least. For each level, the sagittal endplate concave depth and endplate diameter of females were significantly smaller than those of males (P<0.05). Among all measured segments, C7 had the least coronal concave angle. Gender did not influence coronal concave angle significantly (P>0.05). Increasing from C2 to C7, the endplate transverse diameters of females were significantly smaller than those of males (P<0.05). CONCLUSION: The exact shape and geometry of cervical endplate are crucial for the design and improvement of cervical disc prosthesis. Gender difference of sagittal and transverse diameters of cervical endplate should be given more attention when implanting a disc prosthesis. These endplate geometrical parameters should be taken into consideration when calculating most suitable geometric parameters of new disc prosthesis. PMID- 26852321 TI - Consistent prevalence of asymptomatic infections in malaria endemic populations in Colombia over time. AB - BACKGROUND: Malaria control programmes rely on confirmation of parasite presence in patients' blood prior to treatment administration. Plasmodium parasites are detected mostly by microscopy or rapid diagnostic test (RDT). Although these methods contribute significantly to malaria control/elimination, they are not suitable for detecting the significant proportion of asymptomatic subjects harbouring low levels of parasitaemia, which endure untreated as potential reservoirs for transmission. Malaria prevalence was assessed in endemic regions of Colombia over a 4-year follow-up. METHODS: A series of cross-sectional surveys were conducted between 2011 and 2014 in low to moderate malaria transmission sentinel sites (SS) of Tumaco, Buenaventura and Tierralta municipalities of Colombia. A census was performed and a random sample of houses was selected from each SS prior to each survey. Inhabitants were asked to answer a questionnaire on clinical, epidemiological and demographic aspects, and to provide a blood sample for malaria diagnosis using microscopy and quantitative real time polymerase chain reaction (qPCR). RESULTS: A total of 3059 blood samples were obtained from all SS, 58.5 % of which were from women and displayed a malaria prevalence ranging from 4 % (95 % CI 3-5 %) to 10 % (95 % CI 8-12 %) in the 4 years' study period. Almost all malaria cases (n = 220, 97 %) were sub-microscopic and only detectable by qPCR; 90 % of the cases were asymptomatic at the time of blood collection. While Buenaventura and Tierralta had a decreasing tendency during the follow-up, Tumaco had a rise in 2013 and then a decrease in 2014. Plasmodium vivax accounted for the majority (66-100 %) of cases in Tierralta and Buenaventura and for 25-50 % of the cases in Tumaco. CONCLUSIONS: This study demonstrates an important prevalence of asymptomatic malaria cases not detectable by microscopy, which therefore remain untreated representing a parasite pool for malaria transmission. This demands the introduction of alternative strategies for diagnosis and treatment, especially for areas of low transmission to reduce it to appropriate levels for malaria pre-elimination efforts to start. PMID- 26852323 TI - Posterior cortical atrophy as a primary clinical phenotype of corticobasal syndrome with a progranulin gene rs5848 TT genotype. AB - Posterior cortical atrophy (PCA) represents a special clinicoradiologic syndrome characterized by progressive visuospatial and visuoperceptual deficits. PCA and corticobasal syndrome (CBS) may share similar pathogenetic mechanisms. We report the clinical, neuropsychological, imaging, and genetic features of a patient with initial visual problems, who further developed other cognitive impairments and asymmetric extrapyramidal signs fitting into the diagnosis of CBS. Genetic testing revealed homozygous for the T allele of the rs5848 GRN variant. This study provided an evidence for CBS belonging to the clinical spectrum of GRN genetic variant and demonstrated CBS may initially present with symptoms of PCA in rare cases. PMID- 26852322 TI - Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency. AB - BACKGROUND: While antiretroviral therapies have improved life expectancy and reduced viral loads in HIV-1-positive individuals, the cessation of treatment results in a rebound of viral replication. This suggests that a reservoir of latently-infected cells remains within these patients, the identity of which is ill-defined and therefore difficult to target therapeutically. Current strategies are aimed at using drugs such as histone deacetylase (HDAC) inhibitors to induce the expression of latent HIV-1 proviruses in order to activate and ultimately eradicate this reservoir of infected cells. One concern with the use of HDAC inhibitors is that they could up-regulate human endogenous retroviruses (HERVs), as well as HIV-1, with potentially pathophysiological consequences. RESULTS: In this study, we analysed the transcription of HERV genes in HIV-1 latency T cell (J-LAT 8.4) and monocyte (U1) models following treatment with the HDAC inhibitors, vorinostat, panobinostat and romidepsin. We examined the expression of HERV-K (HML-2) env and pol, as well as the co-opted genes HERV-W env (syncytin 1), HERV-FRD env (syncytin-2), in these cell lines. Finally, we investigated HERV expression in primary human T cells. CONCLUSIONS: We show that HDAC inhibitors did not substantially increase the transcription of the analysed HERV env or pol genes, suggesting that histone acetylation is not crucial for controlling HERV expression in these experimental models and in ex vivo primary human T cells. Importantly, this indicates that unwanted HERV expression does not appear to be a barrier to the use of HDAC inhibitors in HIV-1 cure strategies. PMID- 26852324 TI - Determinants of early initiation of breastfeeding in Nigeria: a population-based study using the 2013 demograhic and health survey data. AB - BACKGROUND: Provision of mother's breast milk to infants within one hour of birth is referred to as Early Initiation of Breast Feeding (EIBF) which is an important strategy to reduce perinatal and infant morbidities and mortality. This study aimed to use recent nationally representative survey data to identify individual, household and community level factors associated with EIBF and to update on previous knowlegde with regards to EIBF in Nigeria. METHODS: We used cross sectional data from the 2013 Nigerian Demographic and Health Survey (NDHS). Chi square tests and binary logistic regression were used to test for association between EIBF and individual, household and community level factors. RESULT: The proportion of infants who initiated breastfeeding within 1 h of birth was 34.7% (95% Confidence Interval (CI): 33.9-35.6). In the multivariate analysis, mothers who delivered in a health facility were more likely to initiate breastfeeding early as compared to mothers who delivered at home (Adjusted Odds Ratio (AOR) =1.40, 95% CI = 1.22-1.60). The odds of EIBF was three times higher for mothers who had vaginal delivery as compared to mothers who had caesarean section (AOR = 3.08, 95% CI = 2.14-4.46). Other factors that were significantly associated with increased likelihood of EIBF were; multiparity, large sized infant at birth, not working mothers as compared to mothers working in sales and other sectors, wealthier household index and urban residence. Mothers in the South West were less likely to inititiate breastfeeding within 1 h of birth as compared to the North West, however, the following geopolitical zones; North East, North Central, and South South had higher likelihood of EIBF when compared to the North West geopolitical zone. CONCLUSION: EIBF in Nigeria is not optimal with just about 34.7% of children initiating breastfeeding within one hour of birth, the results suggest that breastfeeding programmes and policies should give special attention to "rural mothers, working mothers, primiparous mothers, mothers with ceasarean deliveries, home deliveries and poor mothers" and this intervention should cut across geopolitical zones with more emphasis to zones with lower rates of EIBF. PMID- 26852325 TI - Effect of cerulenin on fatty acid composition and gene expression pattern of DHA producing strain Colwellia psychrerythraea strain 34H. AB - BACKGROUND: Colwellia psychrerythraea 34H is a psychrophilic bacterium able to produce docosahexaenoic acid (DHA). Polyketide synthase pathway is assumed to be responsible for DHA production in marine bacteria. RESULTS: Five pfa genes from strain 34H were confirmed to be responsible for DHA formation by heterogeneous expression in Escherichia coli. The complexity of fatty acid profile of this strain was revealed by GC and GC-MS. Treatment of cells with cerulenin resulted in significantly reduced level of C16 monounsaturated fatty acid (C16:1(Delta9t), C16:1(Delta7)). In contrast, the amount of saturated fatty acids (C10:0, C12:0, C14:0), hydroxyl fatty acids (3-OH C10:0 and 3-OH C12:0), as well as C20:4omega3, C20:5omega3 and C22:6omega3 were increased. RNA sequencing (RNA-Seq) revealed the altered gene expression pattern when C. psychrerythraea cells were treated with cerulenin. Genes involved in polyketide synthase pathway and fatty acid biosynthesis pathway were not obviously affected by cerulenin treatment. In contrast, several genes involved in fatty acid degradation or beta-oxidation pathway were dramatically reduced at the transcriptional level. CONCLUSIONS: Genes responsible for DHA formation in C. psychrerythraea was first cloned and characterized. We revealed the complexity of fatty acid profile in this DHA producing strain. Cerulenin could substantially change the fatty acid composition by affecting the fatty acid degradation at transcriptional level. Acyl-CoA dehydrogenase gene family involved in the first step of beta-oxidation pathway may be important to the selectivity of degraded fatty acids. In addition, inhibition of FabB protein by cerulenin may lead to the accumulation of malonyl CoA, which is the substrate for DHA formation. PMID- 26852327 TI - Pattern of traumatised anterior teeth among adult Nigerians and complications from late presentation. AB - BACKGROUND: The objectives of this study were to determine the prevalence and pattern of traumatic dental injury (TDI) among adults presenting in a tertiary health care facility in Nigeria, the time interval between injury and presentation in the hospital, the reasons for seeking treatment, and the complications arising due to late presentation. METHODS: Information obtained from history taking and clinical examination included Patient's demographics, the when, where, and how of the injury, previous history of trauma, time elapsed between injury and presentation at the hospital, reason for seeking treatment, tooth/teeth involved, sensibility, tenderness to percussion, mobility, presence of discolouration, swelling, sinus tract, and mobility. Radiographic findings such as periapical radiolucency, pulp canal obliteration, and root resorption were also documented. TDI was classified using the Andreasen's classification. RESULTS: Out of the 2645 adult patients that attended the outpatient clinic, 184 Presented with TDI giving a prevalence of 6.96 %. Their age range and mean age were 17-69 years and 30.6 +/- 11.2 years respectively. Falls accounted for most (26.4 %) of the trauma to anterior teeth followed by motor cycle accidents (18.4 %) and domestic accidents (12.9 %), while opening bottle cork accounted for 1.2 %. The most common type of injury was enamel-dentine fracture accounting for 28.8 %, followed by complicated crown fracture 18.6 %, and avulsion 11.7 %. The maxillary central incisors were the most commonly affected followed by the maxillary lateral incisors and canines. More than half (51.5 %) of the patients presented in the hospital more than 1 year after injury. Majority of patients in the age groups <=20 and 51-60 sought treatment because of pain, while more of those in the age groups 21-30 and 31-40 sought treatment because of aesthetic considerations. Seventy three (45.3 %) of the patients presented with complications involving 138 teeth. Majority of the complications were in teeth with enamel-dentine fracture (93.4 %), followed by concussion injury (55.6 %). CONCLUSIONS: The prevalence of TDI in this study falls within previously reported figures. However, the high number of teeth developing complications may have resulted from late presentation for care. PMID- 26852326 TI - Pathophysiology of the behavioral variant of frontotemporal lobar degeneration: A study combining MRI and FDG-PET. AB - Gray matter (GM) lobar atrophy and glucose hypometabolism are well-described hallmarks of frontotemporal lobar degeneration (FTLD), but the relationships between them are still poorly understood. In this study, we aimed to show the patterns of GM atrophy and hypometabolism in a sample of 15 patients with the behavioral variant of FTLD (bv-FTD), compared to 15 healthy controls, then to provide a direct comparison between GM atrophy and hypometabolism, using a voxel based method specially designed to statistically compare the two imaging modalities. The participants underwent structural magnetic resonance imaging and 18F-fluorodeoxyglucose (FDG) positron emission tomography examinations. First, between-group comparisons of GM volume and metabolism were performed. Then, in the patient group, correlations between regional alterations and direct between modality voxelwise comparison were performed. Finally, we examined individual patterns of brain abnormalities for each imaging modality and each patient. The observed patterns of GM atrophy and hypometabolism were consistent with previous studies. We found significant voxelwise correlations between changes in GM and FDG uptake, mainly in the frontal cortex, corresponding to the typical profile of alterations in bv-FTD. The direct comparison revealed regional variability in the relationship between hypometabolism and atrophy. This analysis revealed greater atrophy than hypometabolism in the right putamen and amygdala, and left insula and superior temporal gyrus, whereas hypometabolism was more severe than GM atrophy in the left caudate nucleus and anterior cingulate cortex. Finally, GM atrophy affected the right amygdala/hippocampus and left insula in 95 % of the patients. These findings provide evidence for regional variations in the hierarchy of hypometabolism and GM atrophy and the relationships between them, and enhance our understanding of the pathophysiology of bv-FTD. PMID- 26852328 TI - SCN2B in the Rat Trigeminal Ganglion and Trigeminal Sensory Nuclei. AB - The beta-2 subunit of the mammalian brain voltage-gated sodium channel (SCN2B) was examined in the rat trigeminal ganglion (TG) and trigeminal sensory nuclei. In the TG, 42.6 % of sensory neurons were immunoreactive (IR) for SCN2B. These neurons had various cell body sizes. In facial skins and oral mucosae, corpuscular nerve endings contained SCN2B-immunoreactivity. SCN2B-IR nerve fibers formed nerve plexuses beneath taste buds in the tongue and incisive papilla. However, SCN2B-IR free nerve endings were rare in cutaneous and mucosal epithelia. Tooth pulps, muscle spindles and major salivary glands were also innervated by SCN2B-IR nerve fibers. A double immunofluorescence method revealed that about 40 % of SCN2B-IR neurons exhibited calcitonin gene-related peptide (CGRP)-immunoreactivity. However, distributions of SCN2B- and CGRP-IR nerve fibers were mostly different in facial, oral and cranial structures. By retrograde tracing method, 60.4 and 85.3 % of TG neurons innervating the facial skin and tooth pulp, respectively, showed SCN2B-immunoreactivity. CGRP immunoreactivity was co-localized by about 40 % of SCN2B-IR cutaneous and tooth pulp TG neurons. In trigeminal sensory nuclei of the brainstem, SCN2B-IR neuronal cell bodies were common in deep laminae of the subnucleus caudalis, and the subnuclei interpolaris and oralis. In the mesencephalic trigeminal tract nucleus, primary sensory neurons also exhibited SCN2B-immunoreactivity. In other regions of trigeminal sensory nuclei, SCN2B-IR cells were very infrequent. SCN2B-IR neuropil was detected in deep laminae of the subnucleus caudalis as well as in the subnuclei interpolaris, oralis and principalis. These findings suggest that SCN2B is expressed by various types of sensory neurons in the TG. There appears to be SCN2B-containing pathway in the TG and trigeminal sensory nuclei. PMID- 26852329 TI - Sequence diversity between class I MHC loci of African native and introduced Bos taurus cattle in Theileria parva endemic regions: in silico peptide binding prediction identifies distinct functional clusters. AB - There is strong evidence that the immunity induced by live vaccination for control of the protozoan parasite Theileria parva is mediated by class I MHC restricted CD8(+) T cells directed against the schizont stage of the parasite that infects bovine lymphocytes. The functional competency of class I MHC genes is dependent on the presence of codons specifying certain critical amino acid residues that line the peptide binding groove. Compared with European Bos taurus in which class I MHC allelic polymorphisms have been examined extensively, published data on class I MHC transcripts in African taurines in T. parva endemic areas is very limited. We utilized the multiplexing capabilities of 454 pyrosequencing to make an initial assessment of class I MHC allelic diversity in a population of Ankole cattle. We also typed a population of exotic Holstein cattle from an African ranch for class I MHC and investigated the extent, if any, that their peptide-binding motifs overlapped with those of Ankole cattle. We report the identification of 18 novel allelic sequences in Ankole cattle and provide evidence of positive selection for sequence diversity, including in residues that predominantly interact with peptides. In silico functional analysis resulted in peptide binding specificities that were largely distinct between the two breeds. We also demonstrate that CD8(+) T cells derived from Ankole cattle that are seropositive for T. parva do not recognize vaccine candidate antigens originally identified in Holstein and Boran (Bos indicus) cattle breeds. PMID- 26852330 TI - Web-TCGA: an online platform for integrated analysis of molecular cancer data sets. AB - BACKGROUND: The Cancer Genome Atlas (TCGA) is a pool of molecular data sets publicly accessible and freely available to cancer researchers anywhere around the world. However, wide spread use is limited since an advanced knowledge of statistics and statistical software is required. RESULTS: In order to improve accessibility we created Web-TCGA, a web based, freely accessible online tool, which can also be run in a private instance, for integrated analysis of molecular cancer data sets provided by TCGA. In contrast to already available tools, Web TCGA utilizes different methods for analysis and visualization of TCGA data, allowing users to generate global molecular profiles across different cancer entities simultaneously. In addition to global molecular profiles, Web-TCGA offers highly detailed gene and tumor entity centric analysis by providing interactive tables and views. CONCLUSIONS: As a supplement to other already available tools, such as cBioPortal (Sci Signal 6:pl1, 2013, Cancer Discov 2:401 4, 2012), Web-TCGA is offering an analysis service, which does not require any installation or configuration, for molecular data sets available at the TCGA. Individual processing requests (queries) are generated by the user for mutation, methylation, expression and copy number variation (CNV) analyses. The user can focus analyses on results from single genes and cancer entities or perform a global analysis (multiple cancer entities and genes simultaneously). PMID- 26852332 TI - A Combination of Remote Ischemic Perconditioning and Cerebral Ischemic Postconditioning Inhibits Autophagy to Attenuate Plasma HMGB1 and Induce Neuroprotection Against Stroke in Rat. AB - Remote ischemic perconditioning (RIPerC) and ischemic postconditioning (IPOC) are well-acknowledged neuroprotective procedures during ischemic injury. The present study established a combined RIPerC and IPOC (RIPerC + IPOC) model in rats and studied how it would regulate the autophagy process and affect HMGB1 levels in a rat model of middle cerebral artery occlusion (MCAO). Rats with MCAO were treated with RIPerC by fastening and release of the left hind limb to achieve 4 cycles of 5 min remote ischemia reperfusion, 40 min prior to cerebral reperfusion, and then treated with IPOC by exposing the cerebral middle artery to 3 cycles of 30 s reperfusion/30 s occlusion at the onset of cerebral reperfusion. Infarction volumes, neurological deficits, and pathological changes were assessed 24 h after ischemia. The autophagy activator rapamycin (RAP) and the autophagy inhibitor 3 methyladenine (3-MA) were administrated for further mechanism. The expression and location of HMGB1 and the autophagy-related proteins like LC3, Beclin1, and P62 as well as plasma HMGB1 levels were measured. Our results suggested that RIPerC + IPOC attenuated plasma HMGB1 levels to intensify its neuroprotective effect against cerebral ischemic reperfusion injury via inhibiting the autophagy process. PMID- 26852331 TI - Protein import complexes in the mitochondrial outer membrane of Amoebozoa representatives. AB - BACKGROUND: An ancestral trait of eukaryotic cells is the presence of mitochondria as an essential element for function and survival. Proper functioning of mitochondria depends on the import of nearly all proteins that is performed by complexes located in both mitochondrial membranes. The complexes have been proposed to contain subunits formed by proteins common to all eukaryotes and additional subunits regarded as lineage specific. Since Amoebozoa is poorly sampled for the complexes we investigated the outer membrane complexes, namely TOM, TOB/SAM and ERMES complexes, using available genome and transcriptome sequences, including transcriptomes assembled by us. RESULTS: The results indicate differences in the organization of the Amoebozoa TOM, TOB/SAM and ERMES complexes, with the TOM complex appearing to be the most diverse. This is reflected by differences in the number of involved subunits and in similarities to the cognate proteins of representatives from different supergroups of eukaryotes. CONCLUSIONS: The obtained results clearly demonstrate structural variability/diversity of these complexes in the Amoebozoa lineage and the reduction of their complexity as compared with the same complexes of model organisms. PMID- 26852333 TI - Exosome-like vesicles released from lipid-induced insulin-resistant muscles modulate gene expression and proliferation of beta recipient cells in mice. AB - AIMS/HYPOTHESIS: The crosstalk between skeletal muscle (SkM) and beta cells plays a role in diabetes aetiology. In this study, we have investigated whether SkM released exosome-like vesicles (ELVs) can be taken up by pancreatic beta cells and can deliver functional cargoes. METHODS: Mice were fed for 16 weeks with standard chow diet (SCD) or with standard diet enriched with 20% palmitate (HPD) and ELVs were purified from quadriceps muscle. Fluorescent ELVs from HPD or SCD quadriceps were injected i.v. or intramuscularly (i.m.) into mice to determine their biodistributions. Micro (mi)RNA quantification in ELVs was determined using quantitative real-time RT-PCR (qRT-PCR)-based TaqMan low-density arrays. Microarray analyses were performed to determine whether standard diet ELVs (SD ELVs) and high palmitate diet ELVs (HPD-ELVs) induced specific transcriptional signatures in MIN6B1 cells. RESULTS: In vivo, muscle ELVs were taken up by pancreas, 24 h post-injection. In vitro, both SD-ELVs and HPD-ELVs transferred proteins and miRNAs to MIN6B1 cells and modulated gene expressions whereas only HPD-ELVs induced proliferation of MIN6B1 cells and isolated islets. Bioinformatic analyses suggested that transferred HPD-ELV miRNAs may participate in these effects. To validate this, we demonstrated that miR-16, which is overexpressed in HPD-ELVs, was transferred to MIN6B1 cells and regulated Ptch1, involved in pancreas development. In vivo, islets from HPD mice showed increased size and altered expression of genes involved in development, including Ptch1, suggesting that the effect of palm oil on islet size in vivo was reproduced in vitro by treating beta cells with HPD-ELVs. CONCLUSIONS/INTERPRETATION: Our data suggest that muscle ELVs might have an endocrine effect and could participate in adaptations in beta cell mass during insulin resistance. PMID- 26852334 TI - Large extracellular space leads to neuronal susceptibility to ischemic injury in a Na+/K+ pumps-dependent manner. AB - The extent of anoxic depolarization (AD), the initial electrophysiological event during ischemia, determines the degree of brain region-specific neuronal damage. Neurons in higher brain regions exhibiting nonreversible, strong AD are more susceptible to ischemic injury as compared to cells in lower brain regions that exhibit reversible, weak AD. While the contrasting ADs in different brain regions in response to oxygen-glucose deprivation (OGD) is well established, the mechanism leading to such differences is not clear. Here we use computational modeling to elucidate the mechanism behind the brain region-specific recovery from AD. Our extended Hodgkin-Huxley (HH) framework consisting of neural spiking dynamics, processes of ion accumulation, and ion homeostatic mechanisms unveils that glial-vascular K(+) clearance and Na(+)/K(+)-exchange pumps are key to the cell's recovery from AD. Our phase space analysis reveals that the large extracellular space in the upper brain regions leads to impaired Na(+)/K(+) exchange pumps so that they function at lower than normal capacity and are unable to bring the cell out of AD after oxygen and glucose is restored. PMID- 26852335 TI - Storing structured sparse memories in a multi-modular cortical network model. AB - We study the memory performance of a class of modular attractor neural networks, where modules are potentially fully-connected networks connected to each other via diluted long-range connections. On this anatomical architecture we store memory patterns of activity using a Willshaw-type learning rule. P patterns are split in categories, such that patterns of the same category activate the same set of modules. We first compute the maximal storage capacity of these networks. We then investigate their error-correction properties through an exhaustive exploration of parameter space, and identify regions where the networks behave as an associative memory device. The crucial parameters that control the retrieval abilities of the network are (1) the ratio between the number of synaptic contacts of long- and short-range origins (2) the number of categories in which a module is activated and (3) the amount of local inhibition. We discuss the relationship between our model and networks of cortical patches that have been observed in different cortical areas. PMID- 26852336 TI - Emu oil offers protection in Crohn's disease model in rats. AB - BACKGROUND: Emu oil is a product of animal origin used for the treatment of inflammation, burns etc. as a part of aboriginal medicine in Australia. Crohn's disease is a common inflammatory manifestation in humans and other animal species relating to the ulceration and digestive disturbances in upper gastro-intestinal tract. Aloe vera is commonly used substance from plant sources for inflammation, wound healing and various other properties. Given the difference in the source of the substances all the while playing a similar therapeutic role in different parts of the world, the present investigation was undertaken to evaluate the protective effect of aloe vera and emu oil alone and in combination; in comparison to sulfasalazine (Allopathic drug) as an alternative for the treatment of Crohn's disease. METHODS: Wistar albino rats were divided into six groups with two sub-groups of six animals each. After pre-treating the animals with sulfasalazine, aloe vera, emu oil and their combination for five consecutive days, the animals were sub-cutaneously administered indomethacin on 4(th) and 5(th) day and each sub-group was sacrificed on day 6 and 9. After sacrifice, serum and intestine of these animals was collected. Intestine length from duodenum till caecum was measured for estimating relative organ weight and disease activity index. Part of intestine was preserved in formalin for histopathology while the rest was used for analysis of oxidative parameters and myeloperoxidase. Serum collected was used for measuring alkaline phosphatase and cholesterol. RESULTS: Assessment of the parameters in treatment groups indicated that the combination of aloe vera and emu oil resulted in better protection by suppressing the oxidative (P < 0.05) and histomorphological changes indicating a enhanced effect of these two agents which was found to be better than sulfasalazine. CONCLUSION: The combination of emu oil and aloe vera exhibited enhanced effect resulting in significant protection from indomethacin induced ulceration. This might be due to the different mechanism of anti-inflammatory effects (Salicylic acid in aloe vera and n3, n6 fatty acids acting as pseudosubstrates to cyclooxygenase enzyme) of components of the animal and plant products tested. PMID- 26852337 TI - The Effectiveness of SMS Reminders on Appointment Attendance: a Meta-Analysis. AB - To identify the efficacy of short message service (SMS) reminders in health care appointment attendance. A systematic review was undertaken to identify studies published between 2005 and 2015 that compared the attendance rates of patients receiving SMS reminders compared to patients not receiving a reminder. Each article was examined for information regarding the study design, sample size, population demographics and intervention methods. A meta-analysis was used to calculate a pooled estimate odds ratio. Twenty-eight (28) studies were included in the review, including 13 (46 %) randomized controlled trials. The pooled odds ratio of the randomized control trials was 1.62 (1.35-1.94). Half of the studies reviewed sent the reminder within 48 h prior to the appointment time, yet no significant subgroups differences with respect to participant age, SMS timing, rate or type, setting or specialty was detectable. All studies, except one with a small sample size, demonstrated a positive OR, indicating SMS reminders were an effective means of improving appointment attendance. There was no significant difference in OR when controlling for when the SMS was sent, the frequency of the reminders or the content of the reminder. SMS appointment reminders are an effective and operative method in improving appointment attendance in a health care setting and this effectiveness has improved over the past 5 years. Further research is required to identify the optimal SMS reminder timing and frequency, specifically in relation to the length of time since the appointment. PMID- 26852338 TI - Post-earthquake Nepal: lessons from Fukushima. PMID- 26852339 TI - The Countdown to 2020: measuring progress in neglected tropical diseases. PMID- 26852341 TI - Assemblies of ionic zinc chlorins assisted by water-soluble polypeptides. AB - Artificial chlorophyll-peptide complexes were prepared by mixing ionic chlorophyll derivatives and oligopeptides in aqueous media containing a small amount of organic solvent. The pigment-peptide complexes provided chlorophyll assemblies showing a sharp red-shifted Qy absorption band concomitant with giant circular dichroism signals. The polypeptide-assisted assemblies of chlorophyllous pigments would afford a good model for photosynthetic apparatuses such as pigment protein complexes of light-harvesting antennas. PMID- 26852342 TI - Idiopathic Fibrosis of the Tunica Muscularis of the Large Intestine in Five Horses with Colic. AB - Histological evidence of fibrosis affecting the outer layer of the large intestinal tunica muscularis was identified in five of 32 horses affected by colic. In three cases, foci of pale eosinophilia and vacuolation of myocytes were observed. These findings are suggestive of a degenerative and fibrotic abnormality in the outer layer of the tunica muscularis of the large intestinal smooth muscle of some horses with colic. PMID- 26852340 TI - Design, synthesis, and biological evaluation of water-soluble amino acid prodrug conjugates derived from combretastatin, dihydronaphthalene, and benzosuberene based parent vascular disrupting agents. AB - Targeting tumor vasculature represents an intriguing therapeutic strategy in the treatment of cancer. In an effort to discover new vascular disrupting agents with improved water solubility and potentially greater bioavailability, various amino acid prodrug conjugates (AAPCs) of potent amino combretastatin, amino dihydronaphthalene, and amino benzosuberene analogs were synthesized along with their corresponding water-soluble hydrochloride salts. These compounds were evaluated for their ability to inhibit tubulin polymerization and for their cytotoxicity against selected human cancer cell lines. The amino-based parent anticancer agents 7, 8, 32 (also referred to as KGP05) and 33 (also referred to as KGP156) demonstrated potent cytotoxicity (GI50=0.11-40nM) across all evaluated cell lines, and they were strong inhibitors of tubulin polymerization (IC50=0.62 1.5MUM). The various prodrug conjugates and their corresponding salts were investigated for cleavage by the enzyme leucine aminopeptidase (LAP). Four of the glycine water-soluble AAPCs (16, 18, 44 and 45) showed quantitative cleavage by LAP, resulting in the release of the highly cytotoxic parent drug, whereas partial cleavage (<10-90%) was observed for other prodrugs (15, 17, 24, 38 and 39). Eight of the nineteen AAPCs (13-16, 42-45) showed significant cytotoxicity against selected human cancer cell lines. The previously reported CA1-diamine analog and its corresponding hydrochloride salt (8 and 10, respectively) caused extensive disruption (at a concentration of 1.0MUM) of human umbilical vein endothelial cells growing in a two-dimensional tubular network on matrigel. In addition, compound 10 exhibited pronounced reduction in bioluminescence (greater than 95% compared to saline control) in a tumor bearing (MDA-MB-231-luc) SCID mouse model 2h post treatment (80mg/kg), with similar results observed upon treatment (15mg/kg) with the glycine amino-dihydronaphthalene AAPC (compound 44). Collectively, these results support the further pre-clinical development of the most active members of this structurally diverse collection of water-soluble prodrugs as promising anticancer agents functioning through a mechanism involving vascular disruption. PMID- 26852343 TI - Cell-block Immunohistochemistry of Bone Marrow Aspirates: a Novel Tool to Improve the Diagnosis of Leishmania Infection in Dogs. AB - Parasitological methods are the most specific procedures used for the diagnosis of Leishmania spp. infection, but their limited sensitivity poses a disadvantage and prompts the need for alternatives. The choice of site for sample collection influences diagnostic sensitivity. The combination of an accurate diagnostic method and a technique that allows large-scale field studies is highly desirable to enhance the investigation of Leishmania spp. infection in dogs, especially in endemic regions. The bone marrow is a good target for the detection of Leishmania spp. in dogs. In this context, bone marrow aspiration is rapid and less invasive compared with biopsy procedures, and also enables cell block processing, paraffin wax embedding and the sectioning of samples for further histological and immunohistochemical analyses. The aim of this study was to describe for the first time parasitological methods (immunohistochemistry [IHC] and histopathology) using the cell block technique with bone marrow aspirates for the diagnosis of Leishmania spp. infection in dogs. Bone marrow aspiration was performed in 45 dogs from an area endemic for visceral leishmaniosis for parasitological culture and the cell block technique (histopathology and IHC). Fourteen (31.1%) dogs tested positive for Leishmania spp. by IHC, six (13.3%) by parasitological culture and four (8.9%) by histopathology. Cell block IHC was a useful tool for the diagnosis of canine visceral leishmaniosis. Further studies should be conducted to validate this method for routine epidemiological screening. PMID- 26852345 TI - Barcoded materials based on photoluminescent hybrid system of lanthanide ions doped metal organic framework and silica via ion exchange. AB - A multicolored photoluminescent hybrid system based on lanthanide ions-doped metal organic frameworks/silica composite host has potential in display and barcode applications. By controlling the stoichiometry of the lanthanides via cation exchange, proportional various lanthanide ions are successfully introduced into metal organic frameworks, whose emission intensity is correspondingly proportional to its amount. The resulting luminescent barcodes depend on the lanthanide ions ratios and compositions. Subsequently, the lanthanide ions located in the channels of metal organic frameworks are protected from any interaction with the environment after the modification of silica on the surface. The optical and thermal stability of the hybrid materials are improved for technological application. PMID- 26852344 TI - In-situ Hybridization for the Detection of Sacbrood Virus in Infected Larvae of the Honey Bee (Apis cerana). AB - The aim of this study was to develop and use in-situ hybridization (ISH) for the detection and localization of the sacbrood virus (SBV) in Korean honey bee (Apis cerana) larvae that were infected naturally with SBV. A 258 base pair cDNA probe for SBV was generated by polymerase chain reaction. Cells positive for viral genome typically showed a dark brown reaction in the cytoplasm. SBV was detected consistently in trophocytes and urocytes. The ISH was successfully applied to routinely fixed and processed tissues and thus should prove helpful in the diagnosis and characterization of viral distribution in infected larvae. PMID- 26852347 TI - Free-standing alpha-Co(OH)2/graphene oxide thin films fabricated through delamination and reassembling of acetate anions intercalated alpha-Co(OH)2 and graphene oxide in water. AB - A novel hydrothermal process is demonstrated to prepare acetate anions intercalated alpha-Co(OH)2 that can be delaminated in water without any additional anion exchange processes. Positively charged Co(OH)2 nanosheets with lateral size of hundreds of nanometers and thickness less than 2 nm can be obtained by dispersing the as-obtained alpha-Co(OH)2 into water followed by sonication. The exfoliated Co(OH)2 nanosheets can be restacked into its original structure with different interlayer d-spacings. A flexible free-standing film with stacking Co(OH)2 nanosheets and graphene oxide (GO) layers can be obtained through flocculation of the Co(OH)2 nanosheets with GO nanosheets suspensions followed by a vacuum filtration, but the content of Co(OH)2 has to be kept under a low value so as to obtain films with flexible nature. Electrochemical tests show that this kind of film is not suitable to be used as electrode material for supercapacitor and lithium ion battery, because the content of active material is not high and the compacted junction between opposite charged nanosheets will prevent the electrolyte from diffusing into the interlayer space. PMID- 26852348 TI - Solution-processable exfoliation and suspension of atomically thin WSe2. AB - HYPOTHESIS: A scalable method for the production of low-dimensional semiconductor materials, such as tungsten diselenide (WSe2), is crucial for applications in flexible and transparent optoelectronic devices. Liquid exfoliation technique can be employed to fabricate a colloidal suspension of WSe2 nanosheets as a low temperature and solution-processable route. EXPERIMENTS: The production of atomically thin WSe2 by liquid exfoliation is investigated, focusing the maximization of the concentration in the resulting suspension by selecting the most suitable solvent for this process. Three different strategies are compared: exfoliation in pure solvents, mixed solvent and aqueous solutions with surfactant. FINDINGS: N-methylpyrrolidone, previously reported as suitable solvent for suspension of other layered materials, results in the highest concentration among the pure solvents tested in this work; however a simple mixture of 30% of propan-2-ol in water surpasses its performance offering a low cost alternative. An optimal surface tension of 28 mN m(-1) is proposed and the influence of the molecular size of the solvent is also considered. The use of anionic surfactant in water makes feasible the exfoliation of WSe2 in aqueous solutions. The analysis of different exfoliation approaches under same processing conditions permits adequate comparison between different solvent systems and reveal optimal parameters for high yield liquid exfoliation of WSe2. PMID- 26852346 TI - Structural perturbation of a dipalmitoylphosphatidylcholine (DPPC) bilayer by warfarin and its bolaamphiphilic analogue: A molecular dynamics study. AB - Compounds with nominally similar biological activity may exhibit differential toxicity due to differences in their interactions with cell membranes. Many pharmaceutical compounds are amphiphilic and can be taken up by phospholipid bilayers, interacting strongly with the lipid-aqueous interface whether or not subsequent permeation through the bilayer is possible. Bolaamphiphilic compounds, which possess two hydrophilic ends and a hydrophobic linker, can likewise undergo spontaneous uptake by bilayers. While membrane-spanning bolaamphiphiles can stabilize membranes, small molecules with this characteristic have the potential to create membrane defects via disruption of bilayer structure and dynamics. When compared to the amphiphilic therapeutic anticoagulant, warfarin, the bolaamphiphilic analogue, brodifacoum, exhibits heightened toxicity that goes beyond superior inhibition of the pharmacological target enzyme. We explore, herein, the consequences of anticoagulant accumulation in a dipalmitoylphosphatidylcholine (DPPC) bilayer. Coarse-grained molecular dynamics simulations reveal that permeation of phospholipid bilayers by brodifacoum causes a disruption of membrane barrier function that is driven by the bolaamphiphilic nature and size of this molecule. We find that brodifacoum partitioning into bilayers causes membrane thinning and permeabilization and promotes lipid flip flop - phenomena that are suspected to play a role in triggering cell death. These phenomena are either absent or less pronounced in the case of the less toxic, amphiphilic compound, warfarin. PMID- 26852349 TI - The adsorption of tetracycline and vancomycin onto nanodiamond with controlled release. AB - The unique properties and tailorable surface of detonation nanodiamonds have given rise to an abundance of potential biomedical applications. Very little is known about the details of adsorption/desorption equilibria of drugs on/from nanodiamonds with different purity, surface chemistry, and agglomeration state. The studies presented here delve into the details of adsorption and desorption of tetracycline (TET) and vancomycin (VAN) on nanodiamond, which are critically important for the rational design of the nanodiamond drug delivery systems. The nanodiamonds studied in these experiments were as-received (ND), purified and carboxyl terminated (ND-COOH), and aminated (ND-NH2). The monolayer capacities of the drugs loaded onto the nanodiamonds are reported herein using Langmuir and Freundlich isotherm models. The results from the desorption studies demonstrate that, by changing the pH environment of drug loaded nanodiamond using buffers of pH 4.09, 7.45, 8.02, and a phosphate buffered saline (PBS) solution, the drug release can effectively be triggered. PMID- 26852350 TI - Influence of surface conductivity on the apparent zeta potential of calcite. AB - Zeta potential is a physicochemical parameter of particular importance in describing the surface electrical properties of charged porous media. However, the zeta potential of calcite is still poorly known because of the difficulty to interpret streaming potential experiments. The Helmholtz-Smoluchowski (HS) equation is widely used to estimate the apparent zeta potential from these experiments. However, this equation neglects the influence of surface conductivity on streaming potential. We present streaming potential and electrical conductivity measurements on a calcite powder in contact with an aqueous NaCl electrolyte. Our streaming potential model corrects the apparent zeta potential of calcite by accounting for the influence of surface conductivity and flow regime. We show that the HS equation seriously underestimates the zeta potential of calcite, particularly when the electrolyte is diluted (ionic strength ? 0.01 M) because of calcite surface conductivity. The basic Stern model successfully predicted the corrected zeta potential by assuming that the zeta potential is located at the outer Helmholtz plane, i.e. without considering a stagnant diffuse layer at the calcite-water interface. The surface conductivity of calcite crystals was inferred from electrical conductivity measurements and computed using our basic Stern model. Surface conductivity was also successfully predicted by our surface complexation model. PMID- 26852351 TI - Facile and green approach to prepare fluorescent carbon dots: Emergent nanomaterial for cell imaging and detection of vitamin B2. AB - Carbon dots (CDs) are a new representative in carbonaceous family and have initiated remarkable research interests over the past one decade in a large variety of fields. Herein, we have utilized a facile, one-step carbonization method to prepare fluorescent carbon dots using poly(vinyl alcohol) (PVA) both as a carbon source and as a surface passivating agent. The as prepared CDs emit bright blue fluorescence under ultraviolet illumination. The structure and optical properties of the CDs are thoroughly investigated by several methods such as high-resolution transmission electron microscopy; dynamic light scattering; UV vis, fluorescence and Fourier transform infrared spectroscopy. The CDs exhibit excellent water solubility and demonstrate average hydrodynamic diameter of 11.3 nm, holding great promise for biological applications. The biocompatibility evaluation and in vitro imaging study reveals that the synthesized CDs can be used as effective fluorescent probes in bio-imaging without noticeable cytotoxicity. In addition, a unique sensor for the detection of vitamin B2 in aqueous solution is proposed on the basis of spontaneous fluorescence resonance energy transfer from CD to vitamin B2. These findings therefore suggest that the CDs can find potential applications in cellular imaging along with sensing of vitamin B2. PMID- 26852352 TI - Synthesis, characterization, and visible-light-driven photocatalytic performance of W-SBA15. AB - A series of tungsten-containing mesoporous SBA15 with different tungsten contents were prepared through a direct co-condensation sol-gel method and then analyzed by various techniques. XRD patterns revealed that the original mesoporous morphology was maintained after introducing tungsten species and forms of tungsten species were changed from incorporated tungsten to isolated tungsten species or low oligomeric tungsten oxide species, and finally to crystalline WO3 with the increase of tungsten precursor content, which were also proven by HRTEM images, UV-Vis DRS, and FT-IR spectra. The W-SBA15 samples exhibited satisfactory photocatalytic performance toward degradation of dye Rhodamine B (RhB) and 2,4 dichlorophenol (2,4-DCP). In particular, the best candidate, sample 10%W-SBA15 showed an apparent reaction rate constant for RhB that was nearly 10 times as high as that of bulk WO3. The enhancement of photocatalytic capability was attributed to the mesoporous morphology with enlarged surface areas, negatively charged surface, and favorable tungsten forms such as incorporated tungsten, isolated tungsten or low oligomeric tungsten oxide species. In addition, active radicals trapping experiments and DMPO spin-trapping ESR spectra indicated that photogenerated holes were major oxidative species during photocatalysis. PMID- 26852353 TI - In situ green synthesis of fluorescent monodispersed mesoporous silica spheres/poly(p-phenylenevinylene) composites. AB - A facile one-pot synthesis for the composite materials fabricated from conjugated polymer, poly(p-phenylenevinylene) (PPV), and monodispersed mesoporous silica spheres (MMSS) is demonstrated. Composite materials having superior photoluminescence properties are easily obtained using ethylene glycol as a reaction solvent in which PPV monomers are effectively exchanged with cationic surfactants in MMSS and subsequently polymerized in the solution. The method can prevent serious reduction of photoluminescence properties which occurs inevitably during thermal treatment (200 degrees C) to polymerize PPV. In our method, the temperature of 100 degrees C is enough to obtain the fully polymerized PPV, which is confirmed in Fourier transform infrared (FT-IR) spectrum. Reaction mechanism is verified through direct observation of its distinguishable color changes in the reaction solution and the measurement of surface electrical potential (zeta potential). The obtained results strongly support that PPV chains are impregnated within mesopores in isolated condition, leading to high fluorescence quantum yield (nearly 80%). Compared to the conventional route, this method reduces multistep synthesis to one-step and eliminates high temperature and high vacuum process, leading to the facile eco-friendly procedure. PMID- 26852354 TI - Large-scale synthesis of water-soluble luminescent hydroxyapatite nanorods for security printing. AB - Luminescent hydroxyapatite nanoparticles, which have excellent biocompatibility, excellent photostability, and strong fluorescence, have received increasing attention as bioprobes in cell imaging. However, they are also excellent candidates for use in ink-jet security printing. Successful products for related applications usually require highly crystalline, mono-dispersible hydroxyapatite nanorods with good colloidal stability and high fluorescence in aqueous media. These requirements are hard to simultaneously satisfy using most synthetic methods. In this paper, we report a simple and versatile hydrothermal method that incorporates the use of sodium citrate to prepare water-dispersible Eu(3+)-doped hydroxyapatite nanorods. The hydroxyapatite nanorods obtained using this method are highly crystalline rod-shaped particles with an average length of 50-80 nm and an average diameter of 15-30 nm. Dispersions of these hydroxyapatite nanorods, which are transparent with a slightly milky color under natural light and a bright red color when excited with 241 nm UV light, display zeta potentials of -35 mV and hydrodynamic diameters of 120 nm. These dispersions remain colloidally stable for a few months. Dispersions with these properties could be easily applied to security printing for confidential information storage and anti counterfeiting technologies. PMID- 26852355 TI - A universal magnetic ferrofluid: Nanomagnetite stable hydrosol with no added dispersants and at neutral pH. AB - A facile method to produce highly stable magnetite magnetic fluid at neutral pH without any stabilizing agents, resulting in pure Fe3O4 nanoparticles dispersed in water is described. The hydrosol which consists of only two components - magnetite and water - behaves as a typical ferrofluid, that is, although it responds to a magnetic field, the magnetic particles cannot be phase-separated from the water by that field. No such pure magnetic fluid have been described before, making it a universal carrier which can be easily modified for any application in materials science and chemistry, and in particular for a range of applications where non-corrosivity, low viscosity, and mild conditions are needed, such as in most bioapplications and in nano electro-mechanical systems. Under optimal conditions the hydrosol is stable for at least three months. PMID- 26852356 TI - The influence of a polymer damper on swing-through crutch gait biomechanics. AB - Forearm crutch technology has evolved slowly compared to other assistive mobility devices, despite the highly repetitive nature of forearm crutch gait and the high incidence of overuse injuries. Using 13 able-bodied volunteers between the ages of 19 and 27, we compared the ground reaction forces of a novel crutch design featuring an elastomeric polymer situated below the handle to an identical design without a damper system and to a commercially available generic rigid forearm crutch model. There were no differences in peak vertical force or impulse between crutches. The crutch with the damper system demonstrated a significantly smaller peak braking force and impulse compared to the generic forearm crutch model. However, the crutch with the damper system demonstrated a significantly larger peak propulsive force and impulse compared to both crutch models. This finding indicates that a forearm crutch with a damper system may help to propel the crutch forward when walking on level surfaces, which could impact forward momentum. PMID- 26852357 TI - Analysis of Fulminant Cerebral Edema in Acute Pediatric Encephalitis. AB - BACKGROUND: Acute pediatric encephalitis with fulminant cerebral edema can rapidly become fatal or result in devastating neurological sequelae. METHODS: All cases coded with the discharge diagnosis of acute encephalitis between January 2000 and December 2010 were reviewed. Of the 1038 children with acute pediatric encephalitis, 25 were enrolled in our study with ages ranging from 5 months to 16 years. RESULTS: The major neurological symptoms included an altered level of consciousness (72%), vomiting (60%), and headache (48%). The onset of neurological symptoms to signs of brain herniation ranged from 0 days to 9 days. Nineteen (76%) patients had a seizure 24-48 hours prior to showing signs of fulminant cerebral edema, and 12 (48%) patients developed status epilepticus. Sixteen patients died, and no survivors returned to baseline. Risk factors for seizures and status epilepticus were compared between the fulminant cerebral edema group (n = 25, 19 seizures, including 12 status epilepticus) and control group (nonfulminant cerebral edema) (n = 1013, 444 seizures, including 141 status epilepticus; p = 0.001 for seizures and p < 0.001 for status epilepticus). CONCLUSION: Our findings indicate that preceding seizures and status epilepticus are significant risk factors for fulminant cerebral edema in children with acute encephalitis. PMID- 26852358 TI - Chronic obstructive pulmonary disease with Eosinophilia, an Emerging Phenotype? PMID- 26852359 TI - Surgical resection of splenic metastasis from the adenosquamous gallbladder carcinoma: A case report. AB - INTRODUCTION: Splenic metastasis of gallbladder carcinoma is extremely rare. Specific anatomical, histological, and functional properties of spleen are believed to be responsible for the rarity of solitary splenic metastasis. PRESENTATION OF CASE: We present the case of a 62-year-old female who developed metachronous splenic metastasis of adenosquamous carcinoma of the gallbladder. We performed central bisegmentectomy of the liver for gallbladder carcinoma. The patient subsequently presented 3 months later with isolated splenic metastasis and liver metastasis. Splenectomy and partial hepatectomy was performed at this time. Histological examination confirmed metastatic adenosquamous carcinoma of the gallbladder. No signs of recurrence were observed at 3 months after the second surgery. DISCUSSION: Although splenectomy provides a potential means of radical treatment in patients with isolated splenic metastases, it should be performed with caution as splenic metastatic lesions may represent the initial clinical manifestation of systemic metastases at multiple sites. In this case, radical surgery was performed following the confirmation of no new unresectable metastatic lesions or systemic dissemination. CONCLUSION: This is the first report on the adenosquamous splenic metastasis from the gallbladder carcinoma. Curative resection may be the treatment of choice for prolonging survival in patients with the splenic metastasis of gallbladder carcinoma. PMID- 26852360 TI - A rare cause of ischemic gut: A case report. AB - INTRODUCTION: Mucormycosis is a fungal infection that is a rare cause of gastrointestinal ischemia, usually found in the immunocompromised or patients with extended surgical intensive care unit stay. This case report brings to light the rare presentation of a total gastric infarction secondary to a rare fungal infection where the overall outcome of the patient depends on timely diagnosis and management. CASE PRESENTATION: An elderly Malay female patient in our institution developed severe sepsis. Radiological investigations revealed an intra abdominal source of sepsis likely secondary to total gastric ischemia. Both the abdominal X-ray and computed tomography scan showed evidence of gastric pneumotosis. She was diagnosed with gastric ischemia and underwent a total gastrectomy. However post surgically she continued to deteriorate and passed away 5 days later. CONCLUSION: Recognition of mucormycosis infection is pertinent to commence anti fungal treatment early with timely implementation of subsequent surgical management. Early access to surgery is necessary to improve cure rates in patients with mucormycosis as antifungal treatment alone is usually not adequate for cure. PMID- 26852361 TI - Malignant melanoma arising in melanin-producing medullary thyroid carcinoma. AB - INTRODUCTION: We report a case of malignant melanoma arising in medullary thyroid carcinoma that has not yet been described. PRESENTATION OF CASE: A 66-year-old woman presented with a mass in her thyroid. The resected mass was black in color, and was composed of a mixture of classic medullary thyroid carcinoma and pleomorphic atypical cells containing melanin pigments. The pleomorphic atypical cells were morphologically consistent with malignant melanoma, and expressed Melan-A, HMB-45, and S-100 protein as determined by immunohistochemistry. Some of these cells were also positive for calcitonin and chromogranin A. Although the malignant melanoma metastasized to the lymph nodes, the patient remained free from local recurrence and distant metastasis and the primary malignant melanoma lesion was not identified for up to 11 years after the thyroidectomy. DISCUSSION: 11 melanin-producing MTC cases have been reported to date. In the reported cases, the term "malignant melanoma" was not used, likely because the melanin-containing carcinoma cells were not morphologically consistent with malignant melanoma, but with medullary carcinoma. CONCLUSION: Malignant melanoma arising in MTC may have a favorable prognosis. PMID- 26852362 TI - Adult cystic lymphangioma in the inner quadrant of the breast-Rare location for a rare disease: A case report. AB - INTRODUCTION: Adult cystic lymphangioma of the breast is extremely rare, especially in the breast's upper, inner quadrant. Review of literature is discussed, including etiology, differential diagnosis, workup, and treatment of the disease. PRESENTATION OF CASE: A 20-year-old female presented with a recurrent left breast cyst. Previous aspirations showed no malignancy. Ultrasonography showed a lobulated anechoic lesion with internal debris and thin septations. The patient then underwent a lumpectomy of the left breast cyst, and pathology showed lymphangioma. DISCUSSION: Cystic lymphangiomas of the breast are benign lymphatic malformations. Consistent with the main drainage pattern of the breast, cystic lymphangiomas are typically located in the upper, outer quadrant, tail of Spence, and subareolar area. Radiologic evaluation may include ultrasound, mammogram, and MRI. FNA cytology and core biopsy assist in the diagnosis of breast lymphangioma. Although different treatment options exist, complete surgical excision remains the most effective treatment modality for adult cystic lymphangioma of the breast. CONCLUSION: Breast cystic lymphangioma is an extremely rare condition, especially in the upper, inner quadrant of the breast. The patient had multiple recurrences of the lesion after fine needle aspirations. Proper index of suspicion, prompt diagnosis, and definitive treatment is necessary to prevent recurrence and complications. PMID- 26852363 TI - Discovery of potent and selective CDK8 inhibitors from an HSP90 pharmacophore. AB - Here we describe the discovery and optimization of 3-benzylindazoles as potent and selective inhibitors of CDK8, also modulating CDK19, discovered from a high throughput screening (HTS) campaign sampling the Merck compound collection. The primary hits with strong HSP90 affinity were subsequently optimized to potent and selective CDK8 inhibitors which demonstrate inhibition of WNT pathway activity in cell-based assays. X-ray crystallographic data demonstrated that 3 benzylindazoles occupy the ATP binding site of CDK8 and adopt a Type I binding mode. Medicinal chemistry optimization successfully led to improved potency, physicochemical properties and oral pharmacokinetics. Modulation of phospho STAT1, a pharmacodynamic biomarker of CDK8, was demonstrated in an APC-mutant SW620 human colorectal carcinoma xenograft model following oral administration. PMID- 26852365 TI - Single-Stage Repair of an Unusual Association: Congenital Gerbode Defect, Hypoplastic Aortic Arch, and Partially Anomalous Pulmonary Venous Return in an Infant. AB - We present the case of a two-month-old male with congenital Gerbode defect, hypoplastic aortic arch, and left-sided partially anomalous pulmonary venous return. The patient underwent single-stage surgical repair, which consisted of aortic arch advancement with resection of the coarctation segment, pulmonary vein repair, and primary closure of the Gerbode defect. The anomalous pulmonary vein posed a particular challenge due to its size and distance from the left atrium, which we approached with a posterior atrial wall trapdoor baffle technique, without mobilizing the affected vein. Postoperatively and at one year follow-up, there was no evidence of residual lesions and there was unobstructed flow pattern across the aortic arch and the affected pulmonary vein. PMID- 26852364 TI - Synthesis and evaluation of orally active small molecule HIV-1 Nef antagonists. AB - The HIV-1 Nef accessory factor enhances viral replication and promotes immune system evasion of HIV-infected cells, making it an attractive target for drug discovery. Recently we described a novel class of diphenylpyrazolodiazene compounds that bind directly to Nef in vitro and inhibit Nef-dependent HIV-1 infectivity and replication in cell culture. However, these first-generation Nef antagonists have several structural liabilities, including an azo linkage that led to poor oral bioavailability. The azo group was therefore replaced with either a one- or two-carbon linker. The resulting set of non-azo analogs retained nanomolar binding affinity for Nef by surface plasmon resonance, while inhibiting HIV-1 replication with micromolar potency in cell-based assays without cytotoxicity. Computational docking studies show that these non-azo analogs occupy the same predicted binding site within the HIV-1 Nef dimer interface as the original azo compound. Computational methods also identified a hot spot for inhibitor binding within this site that is defined by conserved HIV-1 Nef residues Asp108, Leu112, and Pro122. Pharmacokinetic evaluation of the non-azo B9 analogs in mice showed that replacement of the azo linkage dramatically enhanced oral bioavailability without substantially affecting plasma half-life or clearance. The improved oral bioavailability of non-azo diphenylpyrazolo Nef antagonists provides a starting point for further drug lead optimization in support of future efficacy testing in animal models of HIV/AIDS. PMID- 26852366 TI - Interventions Involving the Use of Covered Coronary Artery Stents for Pseudoaneurysms of Blalock-Taussig Shunts. AB - One of the most rare and dangerous complications of a modified Blalock-Taussig shunt involves the formation of a pseudoaneurysm. A pseudoaneurysm may rupture or may result in other adverse events including compression of mediastinal structures or collapse of the underlying lung parenchyma. Shunt-related pseudoaneurysm may be associated with shunt occlusion, bacteremia, or pulmonary hemorrhage. We describe two cases complicated by large pseudoaneurysm formation, following systemic-to-pulmonary artery shunt operations. The patients in question had recurrent pulmonary hemorrhage. Both underwent successful placement of covered coronary artery stents. PMID- 26852367 TI - Tetralogy of Fallot With Left Pulmonary Artery Discontinuity and Totally Anomalous Pulmonary Venous Drainage to the Azygos Vein. AB - We describe a 13-month-old patient with tetralogy of Fallot, left pulmonary artery discontinuity, and supracardiac totally anomalous pulmonary venous drainage to the azygos vein. The diagnosis and the management of this rare association are briefly discussed. PMID- 26852368 TI - Empirically Derived Subgroups of Self-Injurious Thoughts and Behavior: Application of Latent Class Analysis. AB - Latent class analysis was applied to the sample data to identify homogenous subtypes or classes of self-injurious thoughts and behavior (SITB) based on indicators indexing suicide ideation, suicide gesture, suicide attempt, thoughts of nonsuicidal self-injury (NSSI), and NSSI behavior. Analyses were based on a sample of 1,809 healthy adults. Associations between the emergent latent classes and demographic, psychological, and clinical characteristics were assessed. Two clinically relevant subtypes were identified, in addition to a class who reported few SITBs, and were labeled as follows: low SITBs (25.8%), NSSI and ideation (25%), and suicidal behavior (29.2%). Several unique differences between the latent classes and external measures emerged. For instance, those belonging to the NSSI and ideation class compared with the suicidal behavior class reported lower levels of entrapment, burdensomeness, fearlessness about death, exposure to the attempted suicide or self-injury of family members and close friends, and higher levels of goal disengagement and acute agitation. SITBs are best explained by three homogenous subgroups that display quantitative and qualitative differences. Profiling the behavioral and cognitive components of suicidal and nonsuicidal self-injury is potentially useful as a first step in developing tailored intervention and treatment programs. PMID- 26852369 TI - Allergic contact dermatitis due to cosmetics: A clinical and epidemiological study in a tertiary hospital. AB - The incidence of allergic contact dermatitis (ACD) to cosmetics in the general population is rising with the increasing use of cosmetic products and their proliferation and diversification. The aims of this study were to determine the prevalence of ACD to cosmetics in our setting, analyze changes over time, describe the clinical and epidemiological features of this allergic reaction, and identify the allergens and cosmetics involved. We performed a prospective study at the skin allergy unit in Hospital General Universitario de Valencia in Spain between 2005 and 2013 and compared our findings with data collected retrospectively for the period 1996 to 2004. The 5419 patients who underwent patch testing during these 2 periods were included in the study. The mean prevalence of ACD to cosmetics increased from 9.8% in the first period (1996 2004) to 13.9% in the second period (2005-2013). A significant correlation was found between ACD to cosmetics and female sex but not atopy. Kathon CG (blend of methylchloroisothiazolinone and methylisothiazolinone), fragrances, and paraphenylenediamine were the most common causes of ACD to cosmetics during both study periods, and acrylates and sunscreens were identified as emerging allergens during the second period. PMID- 26852371 TI - Are mental health services getting better at responding to abuse, assault and neglect? AB - OBJECTIVE: To determine whether staff responses to abuse disclosures had improved since the introduction of a trauma policy and training programme. METHOD: The files of 250 clients attending four New Zealand mental health centres were audited. RESULTS: There was a significant improvement, compared to an audit prior to the introduction of the policy and training, in the proportion of abuse cases included in formulations, and, to a lesser extent, in treatment plans. There was no significant improvement in the proportion referred for relevant treatment, which remained at less than 25% across abuse categories. The proportion of neglect disclosures responded to was significantly lower than for abuse cases. Fifty percent of the files in which abuse/neglect was recorded noted whether the client had been asked about previous disclosure, and 22% noted whether the client thought there was any connection between the abuse/neglect and their current problems. Less than 1% of cases were reported to legal authorities. People diagnosed with a psychotic disorder were significantly less likely to be responded to appropriately. CONCLUSION: Future training may need to focus on responding well to neglect and people diagnosed with psychosis, on making treatment referrals, and on initiating discussions about reporting to authorities. PMID- 26852370 TI - Skin Cancer Incidence and Mortality in Spain: A Systematic Review and Meta Analysis. AB - INTRODUCTION AND OBJECTIVES: The aim of this systematic review was to describe the incidence and mortality of basal cell carcinoma, squamous cell carcinoma, melanoma, and Merkel cell carcinoma in Spain. MATERIAL AND METHODS: We performed a search of the MEDLINE and Embase databases and reviewed articles from the Spanish Network of Cancer Registries (REDECAN) and the International Agency for Research on Cancer (IARC). The methodological quality of the studies was evaluated and statistical heterogeneity was measured using the I(2) index. A random-effects model was used to perform the meta-analysis because of the heterogeneity of the data. RESULTS: Thirty-two papers were included in the systematic review. The crude incidence rate for basal cell carcinoma was 113.05 (95% CI, 89.03-137.08) cases per 100 000 person-years for the studies based on the registration methodology normally used by registries (in which only 1 tumor with histological confirmation is counted per person). However, the same incidence rate calculated on the basis of clinical and histologic criteria and counting tumors rather than individual patients was 253.23 (95% CI, 273.01 269.45) cases per 100 000 person-years. The incidence was 38.16 (95% CI, 31.72 39.97) cases per 100 000 person-years for squamous cell carcinoma, 8.76 (95% CI, 7.50-10.02) cases per 100 000 person-years for melanoma, and 0.28 (95% CI, 0.15 0.40) cases per 100 000 person-years for Merkel cell carcinoma. CONCLUSIONS: The registration methodology normally used by cancer registries probably underestimates the incidence rates of basal cell and squamous cell carcinoma in Spain. The incidence rates of cutaneous melanoma and Merkel cell carcinoma are lower in Spain than in other European countries. PMID- 26852373 TI - Nutraceuticals with a clinically detectable blood pressure-lowering effect: a review of available randomized clinical trials and their meta-analyses. AB - AIMS: The aim of the present study was to review and comment on the available evidence on nutraceuticals with a clinically demonstrable blood pressure (BP) lowering effect. METHODS: We reviewed studies published in the English language from 1990 to 2015 on dietary supplements or nutraceuticals claiming to show an effect on human BP. An initial list of possibly effective agents and studies was obtained from the online reference, the Natural Medicine Comprehensive Database. Using PubMed, we searched agents identified from this list using the MeSH terms 'hypertension', 'blood pressure', 'dietary supplement' and 'nutraceuticals', alone and in combination. We then focused our attention on meta-analyses and randomized clinical trials. RESULTS: Beyond the well-known effects on BP of the Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet, a large number of studies have investigated the possible BP-lowering effect of different dietary supplements and nutraceuticals, most of which are antioxidant agents with a high tolerability and safety profile. In particular, a relatively large body of evidence supports the use of potassium, magnesium, L-arginine, vitamin C, cocoa flavonoids, beetroot juice, coenzyme Q10, controlled-release melatonin and aged garlic extract. The antihypertensive effect of all these nutraceuticals seems to be dose related and the overall tolerability is good. CONCLUSION: Some nutraceuticals might have a positive impact on BP in humans. Further clinical research is needed, to identify from the available active nutraceuticals those with the best cost-effectiveness and risk-benefit ratio for widespread and long-term use in the general population with a low-added cardiovascular risk related to uncomplicated hypertension. PMID- 26852374 TI - Characterization of mammary adenocarcinomas in male rats after N-methyl-N nitrosourea exposure--Potential for human male breast cancer model. AB - The frequency of breast cancer in men is extremely rare, reported to be less than 1% and there is currently no available animal model for male mammary tumors. We compared the characteristics of various immunohistochemical markers in N-methyl-N nitrosourea (MNU)-induced mammary adenocarcinomas in male and female Crj:CD(SD)IGS rats including: estrogen receptor alpha (ER), progesterone receptor (PgR), androgen receptor (AR), receptor tyrosine-protein kinase erbB-2 (HER2), GATA binding protein 3 (GATA3), and proliferating cell nuclear antigen (PCNA). Female mammary adenocarcinomas were strongly positive in the nuclei of tumor cells for PCNA and ER (100%) with only 60% and 53% expressing PgR and GATA3, respectively. 100% of male adenocarcinomas also exhibited strongly positive expression in the nuclei of tumor cells for PCNA, with 25% expressing AR and only 8% showing positivity for ER. Male carcinomas did not express PgR or GATA3 and none of the tumors, male or female, were positive for HER2. Based on the observed ER and PgR positivity and HER2 negativity within these tumors, MNU-induced mammary adenocarcinomas in female rats appear to be hormonally dependent, similar to human luminal A type breast cancer. In contrast, MNU-induced mammary adenocarcinomas in male rats showed no reactivity for ER, PgR, HER2 or GATA3, suggesting no hormonal dependency. Both male and female adenocarcinomas showed high proliferating activity by PCNA immunohistochemistry. Based on our literature review, human male breast cancers are mainly dependent on ER and/or PgR, therefore the biological pathogenesis of MNU-induced male mammary cancer in rats may differ from that of male breast cancer in humans. PMID- 26852375 TI - A randomized trial to assess the efficacy of a psychoeducational intervention on caregiver burden in schizophrenia. AB - BACKGROUND: Patient's relatives usually care for patients with schizophrenia, and as informal caregivers they experience negative consequences. The aim of the EDUCA-III trial is to test the efficacy of a psychoeducational intervention program (PIP) versus standard care to reduce the caregiver burden at post intervention (4 months), and at follow-up (8 months). METHOD: A two-arm, evaluator blind, multicentre, randomized controlled trial. The PIP group had 12 weekly group sessions. The control intervention group had the usual support and standard care. Primary outcomes were change scores since baseline on the Zarit Burden Interview (ZBI) and the Involvement Evaluation Questionnaire (IEQ). RESULTS: One hundred and nine caregivers were randomized to PIP and 114 to control condition from 23 research sites. The decrease of ZBI scores was significantly higher on the PIP arm at 4 months (mean difference [MD]=-4.33; 95% CI -7.96, -0.71), and at 8 months (MD=-4.46; 95% CI -7.79, -1.13). There were no significant decreases in the IEQ scores (MD at 4 months=-2.80; 95% CI -6.27, 0.67; MD at 8 months=-2.85; 95% CI -6.51, 0.81). CONCLUSIONS: The PIP condition seems to reduce caregiver burden. TRIAL REGISTRATION: ISRCTN32545295. PMID- 26852376 TI - Sulfide as a Mucus Barrier-Breaker in Inflammatory Bowel Disease? AB - The gut epithelium is covered by mucus consisting of mucin polymers connected via disulfide bonds. The mucus layer limits exposure of epithelial cells to toxins and bacteria. A recent study has shown that sulfide, produced by certain bacteria, reduces disulfide bonds in the mucus network. The resulting breaks in the mucus barrier allow exposure of the epithelium to bacteria and toxins, causing inflammation. In this opinion article we argue that this mechanism may be involved in the etiology and/or severity of inflammatory bowel disease (IBD) because IBD is associated with decreased mucus barrier function, altered microbial species, and increased sulfide concentrations. Increasing the mucus integrity by reducing sulfide concentrations in the intestine may be a novel therapeutic option for IBD. PMID- 26852377 TI - [Vertebral pseudometastases secondary to collateral circulation in superior vena cava syndrome]. PMID- 26852372 TI - The contribution of alpha synuclein to neuronal survival and function - Implications for Parkinson's disease. AB - The aggregation of alpha synuclein (alpha-syn) is a neuropathological feature that defines a spectrum of disorders collectively termed synucleinopathies, and of these, Parkinson's disease (PD) is arguably the best characterized. Aggregated alpha-syn is the primary component of Lewy bodies, the defining pathological feature of PD, while mutations or multiplications in the alpha-syn gene result in familial PD. The high correlation between alpha-syn burden and PD has led to the hypothesis that alpha-syn aggregation produces toxicity through a gain-of function mechanism. However, alpha-syn has been implicated to function in a diverse range of essential cellular processes such as the regulation of neurotransmission and response to cellular stress. As such, an alternative hypothesis with equal explanatory power is that the aggregation of alpha-syn results in toxicity because of a toxic loss of necessary alpha-syn function, following sequestration of functional forms alpha-syn into insoluble protein aggregates. Within this review, we will provide an overview of the literature linking alpha-syn to PD and the knowledge gained from current alpha-syn-based animal models of PD. We will then interpret these data from the viewpoint of the alpha-syn loss-of-function hypothesis and provide a potential mechanistic model by which loss of alpha-syn function could result in at least some of the neurodegeneration observed in PD. By providing an alternative perspective on the etiopathogenesis of PD and synucleinopathies, this may reveal alternative avenues of research in order to identify potential novel therapeutic targets for disease modifying strategies. The correlation between alpha-synuclein burden and Parkinson's disease pathology has led to the hypothesis that alpha-synuclein aggregation produces toxicity through a gain-of-function mechanism. However, in this review, we discuss data supporting the alternative hypothesis that the aggregation of alpha-synuclein results in toxicity because of loss of necessary alpha-synuclein function at the presynaptic terminal, following sequestration of functional forms of alpha-synuclein into aggregates. PMID- 26852378 TI - Vessel wall enhancement in the diagnosis and management of primary angiitis of the central nervous system in children. AB - We describe two cases of primary angiitis of the central nervous system in children (cPACNS) diagnosed by vessel wall contrast enhancement on magnetic resonance imaging (MRI). Both patients developed acute cerebral infarction after fever and malaise. In patient 1, a 7-month-old boy, MRI revealed extensive cerebral infarction in the right middle cerebral artery (MCA) area and stenosis at the M1 portion of the right MCA. Oral glucocorticoid therapy was initiated. Vessel wall enhancement was ameliorated 3months after onset, and stenosis was mostly restored. Patient 2, a 5-year-old boy, suffered from cerebral infarction in the left MCA area, and stenosis was identified in the left internal carotid artery, left MCA, and left posterior cerebral artery. Although vessel wall enhancement was reduced after glucocorticoid therapy, vessel wall enhancement of left MCA re-emerged, accompanied by increased erythrocyte sedimentation rate (ESR) and, decreased cerebral blood flow (CBF) in the affected hemisphere. Intravenous methylprednisolone therapy followed by oral glucocorticoid and mycophenolate mofetil resulted in resolution of these findings. Vessel wall enhancement is a promising finding in the diagnosis of cPACNS. Disease flares occur rarely in medium-to-large vessel cPACNS during dose tapering. Vessel wall enhancement, ESR, and CBF may be useful for the assessment of the activity of angiitis. PMID- 26852379 TI - Anterior augmentation plating of aseptic humeral shaft nonunions after intramedullary nailing. AB - INTRODUCTION: Humeral shaft nonunion after intramedullary nailing is a rare but serious complication. Treatment options include implant removal, open plating, exchange nailing and external fixation. The objective of this retrospective study was to determine whether augmentation plating without nail removal is feasible for treating a humeral shaft nonunion. MATERIALS AND METHODS: Between 2002 and 2014, 37 patients (mean age 51, range 20-84 years) with aseptic humeral shaft nonunions prior to intramedullary nailing were treated with augmentation plating. The initial fractures had been fixed with retrograde nails (10 cases) or anterograde nails (27 cases). There were 34 atrophic nonunions and 3 hypertrophic nonunions. Nonunion treatment of all patients consisted of local debridement through an anterior approach to the humerus and anterior placement of the augmentation plates. Supplemental bone grafting was performed in all atrophic nonunion cases. All patients were followed until union was radiologically confirmed. RESULTS: Union was achieved in 36 patients (97 %) after a mean of 6 months (range 3-24 months). There was one case of iatrogenic median nerve palsy that showed complete spontaneous recovery 6 weeks postoperatively. One patient sustained a peri-implant stress fracture that was treated successfully by exchanging the augmentation plate to bridge the nonunion and the fracture. No infections or wound healing complications developed. At a mean follow-up of 14 months, all patients showed free shoulder and elbow motion and no restrictions in daily or working life. CONCLUSIONS: The results indicate that augmentation plating using an anterior approach is a safe and reliable option for humeral shaft nonunions after failed nailing, and the treatment has no substantial complications. Because the healing rates are similar to the standard technique of nail removal and fixation by compression or locking plates, we consider this technique to be an alternative choice for treatment. PMID- 26852380 TI - Which factor is most important for occurrence of cutout complications in patients treated with proximal femoral nail antirotation? Retrospective analysis of 298 patients. AB - INTRODUCTION: Mechanical complications, such as cut-out of the head-neck fixation device, are the most common causes of morbidity after trochanteric femur fracture treatment. The causes of cut-out complications are well defined in patients who are treated with sliding hip screws and biaxial cephalomedullary nails but there are few reports about the patients who are treated with proximal femoral nail antirotation. AIM: The purpose of this study was to evaluate the most important factor about occurance of cutout complication and also to evaluate the risks of the combination of each possible factors. PATIENTS AND METHODS: Overally 298 patients were enrolled in the study. Medical records were reviewed for patients' age, fracture type, gender, anesthesia type and occurance of cut-out complication. Postoperatively taken radiographs were reviewed for tip-apex distance, obtained collo-diaphyseal angle, the quadrant of the helical blade and Ikuta reduction subgroup. The most important factor (s) and also predicted probability of cut-out complication was calculated for each combination of factors. RESULTS: Cut-out complication was observed in 14 patients (4.7 %). The most important factor about occurrence of the cut-out complication was found as varus reduction (p: 0.01), the second important factor was found as implantation of the helical blade in the improper quadrant (p: 0.02). Tip-apex distance was found as third important factor (p: 0.10). The predicted probability of cut-out complication was calculated as 45.6 % when whole of the four surgeon dependent factors were improperly obtained. CONCLUSION: Althought obtaining proper tip-apex distance is important to prevent cutout complication in these fractures, if the fracture is not reduced in varus position and helical blade is inserted in the proper quadrant, possibility of cut-out complication is very low even in the patients with high tip-apex distance. PMID- 26852381 TI - All-age hospitalization rates in coal seam gas areas in Queensland, Australia, 1995-2011. AB - BACKGROUND: Unconventional natural gas development (UNGD) is expanding globally, with Australia expanding development in the form of coal seam gas (CSG). Residents and other interest groups have voiced concerns about the potential environmental and health impacts related to CSG. This paper compares objective health outcomes from three study areas in Queensland, Australia to examine potential environmentally-related health impacts. METHODS: Three study areas were selected in an ecologic study design: a CSG area, a coal mining area, and a rural/agricultural area. Admitted patient data, as well as population data and additional factors, were obtained for each calendar year from 1995 through 2011 to calculate all-age hospitalization rates and age-standardized rates in each of these areas. The three areas were compared using negative binomial regression analyses (unadjusted and adjusted models) to examine increases over time of hospitalization rates grouped by primary diagnosis (19 ICD chapters), with rate ratios serving to compare the within-area regression slopes between the areas. RESULTS: The CSG area did not have significant increases in all-cause hospitalization rates over time for all-ages compared to the coal and rural study areas in adjusted models (RR: 1.02, 95 % CI: 1.00-1.04 as compared to the coal mining area; RR: 1.01, 95 % CI: 0.99-1.04 as compared to the rural area). While the CSG area did not show significant increases in specific hospitalization rates compared to both the coal mining and rural areas for any ICD chapters in the adjusted models, the CSG area showed increases in hospitalization rates compared only to the rural area for neoplasms (RR: 1.09, 95 % CI: 1.02-1.16) and blood/immune diseases (RR: 1.14, 95 % CI: 1.02-1.27). CONCLUSIONS: This exploratory study of all-age hospitalization rates for three study areas in Queensland suggests that certain hospital admissions rates increased more quickly in the CSG study area than in other study areas, particularly the rural area, after adjusting for key sociodemographic factors. These findings are an important first step in identifying potential health impacts of CSG in the Australian context and serve to generate hypotheses for future studies. PMID- 26852382 TI - Comparison of BALB/c and B6-albino mouse strain blastocysts as hosts for the injection of C57BL6/N-derived C2 embryonic stem cells. AB - Embryonic stem (ES) cells from a C57BL/6N (B6N) background injected into B6(Cg) Tyrc-2J/J (B6-albino) recipient blastocysts are commonly used for generating genetically modified mouse models. To understand the influence of the recipient blastocyst strain on germline transmission, BALB/cAnNTac and B6-albino germline transmission rates were compared using the C57BL6/N-derived C2 ES cell line. A total of 92 ES cell clones from 27 constructs were injected. We compared blastocyst yield, birth rate, chimera formation rate, and high-percentage (>50 %) male chimera formation rate. For germline transmission, we analyzed 24 clones from 19 constructs, which generated high-percentage male chimeras from both donor strains. B6-albino hosts resulted in higher mean blastocyst yields per donor than did BALB/c ones (3.6 vs. 2.5). However, BALB/c hosts resulted in a higher birth rate than B6-albino ones (36 vs. 27 %), a higher chimera formation rate (50 vs. 42 %), a higher high-percentage male chimera rate (10 vs. 8 %), and a higher germline transmission rate (65 vs. 49 %), respectively. Our data suggest that BALB/c is a suitable blastocyst host strain for C2 ES cells and has an advantage over the B6-albino strain for receiving the injection of C2 ES cells. PMID- 26852383 TI - Differing views: Can chimpanzees do Level 2 perspective-taking? AB - Although chimpanzees understand what others may see, it is unclear whether they understand how others see things (Level 2 perspective-taking). We investigated whether chimpanzees can predict the behavior of a conspecific which is holding a mistaken perspective that differs from their own. The subject competed with a conspecific over two food sticks. While the subject could see that both were the same size, to the competitor one appeared bigger than the other. In a previously established game, the competitor chose one stick in private first and the subject chose thereafter, without knowing which of the sticks was gone. Chimpanzees and 6 year-old children chose the 'riskier' stick (that looked bigger to the competitor) significantly less in the game than in a nonsocial control. Children chose randomly in the control, thus showing Level 2 perspective-taking skills; in contrast, chimpanzees had a preference for the 'riskier' stick here, rendering it possible that they attributed their own preference to the competitor to predict her choice. We thus run a follow-up in which chimpanzees did not have a preference in the control. Now, they also chose randomly in the game. We conclude that chimpanzees solved the task by attributing their own preference to the other, while children truly understood the other's mistaken perspective. PMID- 26852384 TI - Influence of ground surface characteristics on the mean radiant temperature in urban areas. AB - The effect of variations in land cover on mean radiant temperature (T mrt ) is explored through a simple scheme developed within the radiation model SOLWEIG. Outgoing longwave radiation is parameterised using surface temperature observations on a grass and an asphalt surface, whereas outgoing shortwave radiation is modelled through variations in albedo for the different surfaces. The influence of ground surface materials on T mrt is small compared to the effects of shadowing. Nevertheless, altering ground surface materials could contribute to a reduction in T mrt to reduce the radiant load during heat-wave episodes in locations where shadowing is not an option. Evaluation of the new scheme suggests that despite its simplicity it can simulate the outgoing fluxes well, especially during sunny conditions. However, it underestimates at night and in shadowed locations. One grass surface used to develop the parameterisation, with very different characteristics compared to an evaluation grass site, caused T mrt to be underestimated. The implications of using high temporal resolution (e.g. 15 minutes) meteorological forcing data under partly cloudy conditions are demonstrated even for fairly proximal sites. PMID- 26852385 TI - [Anteroposterior lenticonus in a patient with Alport syndrome]. PMID- 26852386 TI - [Immature retina evolution in a premature infant]. PMID- 26852387 TI - Increased IL-25 levels in the peritoneal fluid of patients with endometriosis. AB - Previous studies have indicated a higher prevalence of allergic disease among women with endometriosis. It is already well established that type 1 allergies develop in a Th2 cytokine environment. Recent studies have shown, however, that IL-25 induces a Th2 development of naive T lymphocytes and is central in the Th2 response. The aim of this case-control study was to investigate the presence of IL-25 in the peritoneal fluid of women suffering from endometriosis. PF was obtained both from women undergoing laparoscopic surgery due to endometriosis (25 cases) and from women wanting sterilisation (19 controls). IL-25 levels were then investigated by ELISA. Women with endometriosis showed significantly higher levels of IL-25 in their PF (p=0.019) compared to controls. IL-25 levels did not correlate with the stage of endometriosis. Both Th2-cells and mast cells express IL-25, which could favor the development of allergies by perpetuating a hypersensitivity reaction. Further, IL-25 may also hold a role as a diagnostic tool. PMID- 26852388 TI - Decidual soluble factors, through modulation of dendritic cells functions, determine the immune response patterns at the feto-maternal interface. AB - Dendritic cells (DCs) can acquire immunogenic or tolerogenic properties depending on intrinsic and tissue environmental factors. We aimed to determine the immunomodulatory effects of decidual soluble factors from abortion- and non abortion-prone mice on DC functions. The decidual cell supernatants (DS) were obtained from abortion-prone and non-abortion-prone mice. Splenic DCs were treated with DS and conalbumin (as an antigen) and injected into the palms of the mice. After five days, regional lymph node cells were collected and cultured in the presence and absence of conalbumin. The proliferation of lymphocyte cells, the frequency of regulatory T cells (Tregs), and the production of IL-4 and IFN gamma were measured by [(3)H]thymidine incorporation, flow cytometry, and ELISA respectively. Our results indicated that DS from both abortion- and non-abortion prone mice decreased the ability of DCs to induce lymphocyte proliferation and IFN-gamma production, while enhanced their capacity to induce Tregs compared with non-treated DCs. Another important finding was that the immunosuppressive effects of DS from abortion-prone mice on DCs for inducing proliferative responses, developing Tregs, and producing IFN-gamma by primed lymphocytes was less than DS from non-abortion-prone mice. We also found that only DS from non-abortion-prone mice could enhance the capacity of DCs to induce IL-4 production by primed lymphocytes. It can be concluded that decidua-secreted factors, by altering DC functions, can determine the pattern of immune responses at the fetomaternal interface and, subsequently, pregnancy outcome. PMID- 26852389 TI - Species distribution and in vitro antimicrobial susceptibility of coagulase negative staphylococci isolated from bovine mastitic milk. AB - BACKGROUND: Coagulase-negative staphylococci (CoNS) are the most common bovine mastitis causing bacteria in many countries. It is known that resistance for antimicrobials is in general more common in CoNS than in Staphylococcus aureus but little is known about the antimicrobial resistance of specific CoNS species. In this study, 400 CoNS isolates from bovine mastitic milk samples were identified to species level using ribotyping and MALDI-TOF MS, and their antimicrobial susceptibility was determined using a commercially available microdilution system. The results were interpreted according to the epidemiological cut-off values by the European Committee on Antimicrobial Susceptibility testing. RESULTS: The most common CoNS species were S. simulans, S. epidermidis, S. chromogenes and S. haemolyticus. Penicillin resistance was the most common type of antimicrobial resistance. Staphylococcus epidermidis was the most resistant among the four major species. Almost one-third of our S. epidermidis isolates were resistant to >2 antimicrobials and close to 7 % were multidrug resistant. The majority of S. epidermidis isolates were resistant to benzylpenicillin. On the contrary, only few S. simulans isolates were penicillin resistant. Phenotypic oxacillin resistance was found in all four main species, and 34 % of the isolates were oxacillin resistant. However, only 21 isolates (5 %) were positive for the mecA gene. Of these, 20 were S. epidermidis and one S. sciuri. mecC positive isolates were not found. CONCLUSION: Staphylococcus epidermidis differed from the three other major CoNS species as resistance to the tested antimicrobials was common, several isolates were multidrug resistant, and 19 % of the isolates carried the mecA gene encoding methicillin resistance. PMID- 26852391 TI - Searching for minimally invasive aortic valve surgery that can compete with a transcatheter approach. PMID- 26852390 TI - Pitfalls of practicing cancer epidemiology in resource-limited settings: the case of survival and loss to follow-up after a diagnosis of Kaposi's sarcoma in five countries across sub-Saharan Africa. AB - BACKGROUND: Survival after diagnosis is a fundamental concern in cancer epidemiology. In resource-rich settings, ambient clinical databases, municipal data and cancer registries make survival estimation in real-world populations relatively straightforward. In resource-poor settings, given the deficiencies in a variety of health-related data systems, it is less clear how well we can determine cancer survival from ambient data. METHODS: We addressed this issue in sub-Saharan Africa for Kaposi's sarcoma (KS), a cancer for which incidence has exploded with the HIV epidemic but for which survival in the region may be changing with the recent advent of antiretroviral therapy (ART). From 33 primary care HIV Clinics in Kenya, Uganda, Malawi, Nigeria and Cameroon participating in the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Consortia in 2009-2012, we identified 1328 adults with newly diagnosed KS. Patients were evaluated from KS diagnosis until death, transfer to another facility or database closure. RESULTS: Nominally, 22% of patients were estimated to be dead by 2 years, but this estimate was clouded by 45% cumulative lost to follow-up with unknown vital status by 2 years. After adjustment for site and CD4 count, age <30 years and male sex were independently associated with becoming lost. CONCLUSIONS: In this community-based sample of patients diagnosed with KS in sub-Saharan Africa, almost half became lost to follow-up by 2 years. This precluded accurate estimation of survival. Until we either generally strengthen data systems or implement cancer-specific enhancements (e.g., tracking of the lost) in the region, insights from cancer epidemiology will be limited. PMID- 26852393 TI - Anti-TNF-alpha agents and serum lipids in inflammatory bowel diseases. PMID- 26852392 TI - Malaria, helminths, co-infection and anaemia in a cohort of children from Mutengene, south western Cameroon. AB - BACKGROUND: Malaria and helminthiases frequently co-infect the same individuals in endemic zones. Plasmodium falciparum and helminth infections have long been recognized as major contributors to anaemia in endemic countries. Several studies have explored the influence of helminth infections on the course of malaria in humans but how these parasites interact within co-infected individuals remains controversial. METHODS: In a community-based longitudinal study from March 2011 to February 2012, the clinical and malaria parasitaemia status of a cohort of 357 children aged 6 months to 10 years living in Mutengene, south-western region of Cameroon, was monitored. Following the determination of baseline malaria/helminths status and haemoglobin levels, the incidence of malaria and anaemia status was determined in a 12 months longitudinal study by both active and passive case detection. RESULTS: Among all the children who completed the study, 32.5 % (116/357) of them had at least one malaria episode. The mean (+/ SEM) number of malaria attacks per year was 1.44 +/- 0.062 (range: 1-4 episodes) with the highest incidence of episodes occuring during the rainy season months of March-October. Children <5 years old were exposed to more malaria attacks [OR = 2.34, 95 % CI (1.15-4.75), p = 0.019] and were also more susceptible to anaemia [OR = 2.24, 95 % CI (1.85-4.23), p = 0.013] compared to older children (5-10 years old). Likewise children with malaria episodes [OR = 4.45, 95 % CI (1.66 11.94), p = 0.003] as well as those with asymptomatic parasitaemia [OR = 2.41, 95 % CI (1.58-3.69) p < 0.001] were susceptible to anaemia compared to their malaria parasitaemia negative counterparts. Considering children infected with Plasmodium alone as the reference, children infected with helminths alone were associated with protection from anaemia [OR = 0.357, 95 % CI (0.141-0.901), p = 0.029]. The mean haemoglobin level (g/dl) of participants co-infected with Plasmodium and helminths was higher (p = 0.006) compared to participants infected with Plasmodium or helminths alone. CONCLUSION: Children below 5 years of age were more susceptible to malaria and anaemia. The high prevalence of anaemia in this community was largely due to malaria parasitaemia. Malaria and helminths co infection was protective against anaemia. PMID- 26852394 TI - High prolactin levels are associated with more delirium in septic patients. AB - PURPOSES: We investigated whether high prolactin levels were associated with delirium in septic patients because neuropsychiatric disorders are frequently associated with hyperprolactinemia. MATERIALS AND METHODS: Prolactin levels were measured daily for 4 days in 101 patients with sepsis. Delirium was assessed using the Richmond Agitation Sedation Scale and the Confusion Assessment Method in the ICU. RESULTS: Delirium developed in 79 patients (78%) and was more common in patients older than 65 years. Prolactin levels were higher in patients with delirium than in those without over the 4 days of observation (P = .032). In patients with delirium, higher prolactin levels were associated with a lower incidence of nosocomial infection (P = .006). Multivariable logistic regression showed that the Sequential Organ Failure Assessment score at intensive care unit admission (odds ratio, 1.24; 95% confidence interval, 1.04-1.48; P = .002) and the combined effect of prolactin levels with age (odds ratio, 1.018; 95% confidence interval, 1.01-1.031; P = .006) were associated with the development of delirium. CONCLUSIONS: High prolactin levels may be a risk factor for delirium in septic patients. PMID- 26852395 TI - Duration of extracorporeal membrane oxygenation is a poor predictor of hospital survival. AB - PURPOSE: Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure. In patients without the option of lung transplantation, prognostication is challenging. We hypothesized that duration of ECMO therapy is inversely correlated with the chance of recovery and therefore hospital survival. MATERIALS AND METHODS: A single-center retrospective register analysis was performed. All bridge-to-recovery venovenous ECMO patients without option for lung transplantation treated between October 2010 and September 2015 were included. FINDINGS: A total of 175 patients (mean age, 51.61 +/- 2.11 years) were detected. Medium time on ECMO was 9.26 +/- 1.91 days. Time on ECMO was not significantly shorter in survivors compared to nonsurvivors (8.23 +/- 2.04 and 10.15 +/- 3.07, respectively; P = .327). Rate of hospital survival and time on ECMO did not correlate (P = .103). The predictive value of ECMO duration on hospital survival was 0.503 in a receiver operating characteristic analysis. CONCLUSIONS: According to our registry data, duration of ECMO therapy by itself could not predict hospital survival. Prospective studies are needed to confirm this finding. PMID- 26852396 TI - Design construction and analysis of solar ridge concentrator photovoltaic (PV) system to improve battery charging performance. AB - A ridge concentrator photovoltaic system for a 10W multi-crystalline solar panel was designed with the concentration ratios of 1X and 2X. The ray tracing model of ridge concentrator photovoltaic system was carried out using Trace-Pro simulation. The optimum tilt angle for the concentrator PV system throughout the year was computed. The electrical parameters of the 3 panels were analyzed. The effect of temperature on the electrical performance of the panel was also studied. The reduction of voltage due to increasing panel temperature was managed by MPES type Charge controller. Glass reflector with reflectivity 0.95 was chosen as the ridge wall for the concentrator system. The maximum power outputs for the 1X and 2X panel reached were 9W and 10.5W with glass reflector. The percentage of power improvement for 1X and 2X concentrations were 22.3% and 45.8% respectively. The 2X concentrated panel connected battery takes lower time to charge compared with normal panel connected battery. PMID- 26852397 TI - A Pre-Hospital Patient Education Program Improves Outcomes of Bariatric Surgery. AB - BACKGROUND: We designed an assessment and education program which was delivered to patients prior to first outpatient appointment for bariatric surgery. We hypothesised that this program would streamline care and would lead to improved weight loss following bariatric surgery. METHODS: The program incorporates a structured general practitioners (GP) review, a patient information evening and an on-line learning package. It was introduced in September 2012. Patient flow through the program was recorded. Outcomes of the new program were compared with contemporaneously treated patients who did not undertake the pre-hospital program. RESULTS: All 636 patients on the waiting list for first appointment at the Alfred Health bariatric surgery clinic were invited to participate. There were 400 patients ultimately removed from the waiting list for first appointment. Of the remaining 236 patients, 229 consented to participate in the new program. The mean BMI was 47.8 +/- 9.2. The fail to attend first appointment rate dropped from 12 to 2.1 %. At 12 months post-bariatric surgery, patients who undertook the new program (n = 82) had a mean excess weight loss (EWL) of 41.1 +/- 20.3 % where as those treated on the standard pathway (n = 61) had a mean EWL 32 +/- 18.0 % (p = 0.012). CONCLUSIONS: The introduction of a pre-hospital education program has led to an improvement in attendance rates and early weight loss post-bariatric surgery. PMID- 26852398 TI - Short-Term UVB Treatment or Intramuscular Cholecalciferol to Prevent Hypovitaminosis D After Gastric Bypass-a Randomized Clinical Trial. AB - BACKGROUND: Gastric bypass is increasingly used worldwide to treat morbidly obese patients with good results. However, several studies have reported low levels of vitamin D in spite of supplementation. In this randomized clinical trial, we have evaluated two principally different interventions, short-term UVB treatment or a single cholecalciferol injection, to prevent hypovitaminosis D. METHODS: Seventy three patients, randomly treated by UVB (n = 26) or injection (n = 20), and compared to controls (n = 27), were followed for 6 months. Both interventions, 12 treatments of whole-body narrowband UVB and an intramuscular injection of 600,000 IU cholecalciferol, were given in December, when natural sunlight is limited. Blood samples for 25-OH-vitamin D (25[OH]D), intact PTH, calcium, and albumin were obtained at baseline, after 1 and 3 months, and after 6 months for the intervention groups. 25[OH]D was analyzed using a HPLC method. RESULTS: At baseline, 77.2 % of the patients had 25[OH]D <75 nmol/L. At 3 months, both UVB and cholecalciferol injection resulted in significantly higher 25[OH]D levels than controls (71.6 and 77.9 vs. 48.6 nmol/L, p < 0.05). The levels remained rather constant at 6 months (69.0 and 76.7 nmol/L, respectively); however, only injection therapy resulted in improved levels compared to baseline (55.7 nmol/L, p < 0.001). No toxic effects, nor significant changes in PTH or albumin-adjusted calcium, were seen. CONCLUSIONS: In this randomized trial, both interventions, UVB and cholecalciferol, given as an adjunct to oral supplementation in gastric bypass patients, increased the levels of 25[OH]D. Simplicity makes injection therapy suitable for maintaining vitamin D levels during the Nordic winter. PMID- 26852399 TI - Changes in lipid composition during sexual development of the malaria parasite Plasmodium falciparum. AB - BACKGROUND: The development of differentiated sexual stages (gametocytes) within human red blood cells is essential for the propagation of the malaria parasite, since only mature gametocytes will survive in the mosquito's midgut. Hence gametocytogenesis is a pre-requisite for transmission of the disease. Physiological changes involved in sexual differentiation are still enigmatic. In particular the lipid metabolism-despite being central to cellular regulation and development-is not well explored. METHODS: Here the lipid profiles of red blood cells infected with the five different sexual stages of Plasmodium falciparum were analysed by mass spectrometry and compared to those from uninfected and asexual trophozoite infected erythrocytes. RESULTS: Fundamental differences between erythrocytes infected with the different parasite stages were revealed. In mature gametocytes many lipids that decrease in the trophozoite and early gametocyte infected red blood cells are regained. In particular, regulators of membrane fluidity, cholesterol and sphingomyelin, increased significantly during gametocyte maturation. Neutral lipids (serving mainly as caloriometric reserves) increased from 3 % of total lipids in uninfected to 27 % in stage V gametocyte infected red blood cells. The major membrane lipid class (phospholipids) decreased during gametocyte development. CONCLUSIONS: The lipid profiles of infected erythrocytes are characteristic for the particular parasite life cycle and maturity stages of gametocytes. The obtained lipid profiles are crucial in revealing the lipid metabolism of malaria parasites and identifying targets to interfere with this deadly disease. PMID- 26852400 TI - Do efforts to standardize, assess and improve the quality of health service provision to adolescents by government-run health services in low and middle income countries, lead to improvements in service-quality and service-utilization by adolescents? AB - BACKGROUND: Researchers and implementers working in adolescent health, and adolescents themselves question whether government-run health services in conservative and resource-constrained settings can be made adolescent friendly. This paper aims to find out what selected low and middle income country (LMIC) governments have set out to do to improve the quality of health service provision to adolescents; whether their efforts led to measurable improvements in quality and to increased health service-utilization by adolescents. METHODS: We gathered normative guidance and reports from eight LMICs in Asia, Africa, Central and Eastern Europe and the Western Pacific. We analysed national quality standards for adolescent friendly health services, findings from the assessments of the quality of health service provision, and findings on the utilization of health services. RESULTS: Governments of LMICs have set out to improve the accessibility, acceptability, equity, appropriateness and effectiveness of health service provision to adolescents by defining standards and actions to achieve them. Their actions have led to measurable improvements in quality and to increases in health service utilisation by adolescents. CONCLUSIONS: With support, government-run health facilities in LMICs can improve the quality of health services and their utilization by adolescents. PMID- 26852401 TI - Aerobic exercise for cognitive deficits in schizophrenia - The impact of frequency, duration, and fidelity with target training intensity. PMID- 26852402 TI - Abnormal white matter microstructure in drug-naive first episode schizophrenia patients before and after eight weeks of antipsychotic treatment. AB - BACKGROUND: Abnormal white matter integrity has been reported among first episode schizophrenia patients. However, findings on whether it can be reversed by short term antipsychotic medications are inconsistent. METHOD: Diffusion tensor imaging (DTI) was obtained from 55 drug-naive first episode schizophrenia patients and 61 healthy controls, and was repeated among 25 patients and 31 controls after 8 weeks during which patients were medicated with antipsychotics. White matter integrity is measured using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). These measures showing a group difference by Tract-based spatial statistics (TBSS) at baseline were extracted for longitudinal comparisons. RESULTS: At baseline, patients exhibited lower FA, higher MD and higher RD versus controls in forceps, left superior longitudinal fasciculus, inferior fronto-occipital fasciculus, left corticospinal tract, left uncinate fasciculus, left anterior thalamic radiation, and bilateral inferior longitudinal fasciculi. FA values of schizophrenia patients correlated with their negative symptoms (r=-0.412, P=0.002), working memory (r=0.377, P=0.005) and visual learning (r=0.281, P=0.038). The longitudinal changes in DTI indices in these tracts did not differ between patients and controls. However, among the patients the longitudinal changes in FA values in left superior longitudinal fasciculus correlated with the change of positive symptoms (r= 0.560, p=0.004), and the change of processing speed (r=0.469, p=0.018). CONCLUSIONS: White matter deficits were validated in the present study by a relatively large sample of medication naive and first episode schizophrenia patients. They could be associated with negative symptoms and cognitive impairment, whereas improvement in white matter integrity of left superior longitudinal fasciculus correlated with improvement in psychosis and processing speed. Further examination of treatment-related changes in white matter integrity may provide clues to the mechanism of antipsychotic response and provide a biomarker for clinical studies. PMID- 26852403 TI - Cognitive Assessment Interview (CAI): Validity as a co-primary measure of cognition across phases of schizophrenia. AB - BACKGROUND: Progress has been made in developing interview-based measures for the assessment of cognitive functioning, such as the Cognitive Assessment Interview (CAI), as co-primary measures that compliment objective neurocognitive assessments and daily functioning. However, a few questions remain, including whether the relationships with objective cognitive measures and daily functioning are high enough to justify the CAI as an co-primary measure and whether patient only assessments are valid. METHODS: Participants were first-episode schizophrenia patients (n=60) and demographically-similar healthy controls (n=35), chronic schizophrenia patients (n=38) and demographically similar healthy controls (n=19). Participants were assessed at baseline with an interview-based measure of cognitive functioning (CAI), a test of objective cognitive functioning, functional capacity, and role functioning at baseline, and in the first episode patients again 6 months later (n=28). RESULTS: CAI ratings were correlated with objective cognitive functioning, functional capacity, and functional outcomes in first-episode schizophrenia patients at similar magnitudes as in chronic patients. Comparisons of first-episode and chronic patients with healthy controls indicated that the CAI sensitively detected deficits in schizophrenia. The relationship of CAI Patient-Only ratings with objective cognitive functioning, functional capacity, and daily functioning were comparable to CAI Rater scores that included informant information. CONCLUSIONS: These results confirm in an independent sample the relationship of the CAI ratings with objectively measured cognition, functional capacity, and role functioning. Comparison of schizophrenia patients with healthy controls further validates the CAI as an co-primary measure of cognitive deficits. Also, CAI change scores were strongly related to objective cognitive change indicating sensitivity to change. PMID- 26852404 TI - TDCS produces incremental gain when combined with working memory training in patients with schizophrenia: A proof of concept pilot study. PMID- 26852405 TI - The Length of Child Anxiety Treatment in a Regional Health System. AB - Anxiety disorders are often undertreated due to unsuccessful dissemination of evidence-based treatments (EBTs). Lack of empirical data regarding the typical length of treatment in clinical settings may hamper the development of clinically relevant protocols. The current study examined billing records for 335 children ages 7-17 years to quantify the treatment received for newly diagnosed anxiety disorders within a regional health system. The vast majority of patients did not receive a sufficient number of appointments to complete the typical cognitive behavioral therapy protocol or reach the sessions introducing exposure. Although half of the sample received pharmacotherapy, the vast majority received fewer follow-up appointments than participants in pharmacotherapy research studies. Further, the type of treatment (i.e., number of sessions and medication) differed depending on utilization of specialty care. These results underscore the need to develop brief and flexible EBT protocols that can be standardized and implemented in community practice. PMID- 26852406 TI - Knowledge, attitudes and perceptions of occupational hazards and safety practices in Nigerian healthcare workers. AB - BACKGROUND: By profession, healthcare workers (HCWs) attend to clients and patients through a variety of preventive and curative services. However, while their attention is focused on providing care, they are vulnerable to hazards that could be detrimental to their health and well-being. This is especially true in developing countries where health service delivery is fraught with minimal protective precautions against exposures to numerous fomites and infectious agents. This study assessed the workplace hazards and safety practices by selected HCWs in a typical health care facility (HCF) in Nigeria. METHODS: The study utilized a descriptive cross-sectional design and stratified sampling technique to identify 290 respondents. The study used mixed methodology and collected data by validated instruments with resulting data analyzed by IBM-SPSS, version 20. RESULTS: The results showed that over half of the respondents were registered nurses, female, married (61.7 %) with 5 years median work experience (70.3 %). Most respondents (89 %) were knowledgeable about hazards in HCFs, identified recapping used needles as a risky practice (70 %) and recognized that effective hand washing prior to, and after every clinical procedure in preventing cross infection (100 %). Also, most respondents (96.2 %) believed they were at risk of occupational hazards while about two-thirds perceived the risk as high. In addition, only 64.2 and 87.2 % had completed Hepatitis B and Tetanus immunizations, respectively. Only 52.1 % "always" complied with standard procedures and most (93.8 %) practice safe disposal of sharps (93.8 %) while those that did not (40 %) generally implicated lack of basic safety equipment. In this study, the practice of hand washing by respondents was not influenced by occupation and education. CONCLUSIONS: The high level of knowledge demonstrated by respondents was at variance with practice, therefore, measures aimed at promoting safety practices and, minimizing exposure to hazards such as; provision of safety equipment, pre-placement and routine training of staff on safety practices and adequate reinforcement of staff capacity and capability through drills in all HCFs should be institutionalized and made mandatory. The protocol of the safety training and drills should be responsive to evidence-based emerging and sectoral safety challenges. PMID- 26852407 TI - Erratum to: Alcohol dehydrogenase gene ADH3 activates glucose alcoholic fermentation in genetically engineered Dekkera bruxellensis yeast. PMID- 26852408 TI - Simultaneous detection of bioavailable arsenic and cadmium in contaminated soils using dual-sensing bioreporters. AB - Whole-cell bioreporters (WCBs) have attracted increasing attention during the last few decades because they allow fast determination of bioavailable heavy metals in contaminated sites. Various WCBs to monitor specific heavy metals such as arsenic and cadmium in diverse environmental systems are available. However, currently, no study on simultaneous analysis of arsenic and cadmium has been reported, even though soils are contaminated by diverse heavy metals and metalloids. We demonstrated herein the development of dual-sensing WCBs to simultaneously quantify bioavailable arsenic and cadmium in contaminated sites by employing the promoter regions of the ars and znt operons as separate metal sensing domains, and egfp and mcherry as reporter genes. The dual-sensing WCBs were generated by inserting two sets of genes into E. coli DH5alpha. The capability of WCBs was successfully proved to simultaneously quantify bioavailable arsenic and cadmium in amended Landwirtschaftliche Untersuchungs und Forschungsanstalt (LUFA) soils, and then, it was applied to contaminated field soils collected from a smelter area in Korea. As a result, it was noticed that the bioavailable portion of cadmium was higher than that of arsenic while the absolute amount of bioavailable arsenic and cadmium level was opposite. Since both cadmium and arsenic were assessed from the same E. coli cells, the data obtained by using dual-sensing WCBs would be more efficient and convenient than that from comparative WCB assay. In spite of advantageous aspects, to our knowledge, this is the first report on a dual-sensing WCB for rapid and concurrent quantification of bioavailable arsenic and cadmium in contaminated soils. PMID- 26852409 TI - Improving isopropanol tolerance and production of Clostridium beijerinckii DSM 6423 by random mutagenesis and genome shuffling. AB - Random mutagenesis and genome shuffling was applied to improve solvent tolerance and isopropanol/butanol/ethanol (IBE) production in the strictly anaerobic bacteria Clostridium beijerinckii DSM 6423. Following chemical mutagenesis with N methyl-N-nitro-N-nitrosoguanidine (NTG), screening of putatively improved strains was done by submitting the mutants to toxic levels of inhibitory chemicals or by screening for their tolerance to isopropanol (>35 g/L). Suicide substrates, such as ethyl or methyl bromobutyrate or alcohol dehydrogenase inhibitors like allyl alcohol, were tested and, finally, 36 mutants were isolated. The fermentation profiles of these NTG mutant strains were characterized, and the best performing mutants were used for consecutive rounds of genome shuffling. Screening of strains with further enhancement in isopropanol tolerance at each recursive shuffling step was then used to spot additionally improved strains. Three highly tolerant strains were finally isolated and able to withstand up to 50 g/L isopropanol on plates. Even if increased tolerance to the desired end product was not always accompanied by higher production capabilities, some shuffled strains showed increased solvent titers compared to the parental strains and the original C. beijerinckii DSM 6423. This study confirms the efficiency of genome shuffling to generate improved strains toward a desired phenotype such as alcohol tolerance. This tool also offers the possibility of obtaining improved strains of Clostridium species for which targeted genetic engineering approaches have not been described yet. PMID- 26852410 TI - Prevalence of heart failure in Australia: a systematic review. AB - BACKGROUND: In the absence of a systematic collection of data pertaining to heart failure, summarizing the data available from individual studies provides an opportunity to estimate the burden of heart failure. The present study systematically reviewed the literature to estimate the incidence and prevalence rates of heart failure in Australia. METHODS: Studies reporting on prevalence or incidence of heart failure published between 1990 and 2015 were identified through a systematic search of Embase, PubMed, Ovid Medline, MeSH, Scopus and websites of the Australian Institute of Health, and Welfare and Australian Bureau of Statistics. RESULTS: The search yielded a total of 4978 records, of which thirteen met the inclusion criteria. There were no studies reporting on the incidence of heart failure. The prevalence of heart failure in the Australian population ranged between 1.0% and 2.0%, with a significant proportion of cases being previously undiagnosed. The burden of heart failure was higher among Indigenous than non-Indigenous Australians (age-standardized prevalence rate ratio of 1.7). Heart failure was prevalent in women than men, and in rural and remote regions than in the metropolitan and capital territories. CONCLUSION: This systematic review highlights the limited available data on the epidemiology of heart failure in Australia. Population level studies, using standardized approaches, are needed in order to precisely describe the burden of HF in the population. PMID- 26852411 TI - Succinobucol, a Non-Statin Hypocholesterolemic Drug, Prevents Premotor Symptoms and Nigrostriatal Neurodegeneration in an Experimental Model of Parkinson's Disease. AB - Parkinson's disease (PD) is a neurodegenerative disorder characterized by non motor and motor disabilities. This study investigated whether succinobucol (SUC) could mitigate nigrostriatal injury caused by intranasal 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) administration in mice. Moreover, the effects of SUC against MPTP-induced behavioral impairments and neurochemical changes were also evaluated. The quantification of tyrosine hydroxylase-positive (TH+) cells was also performed in primary mesencephalic cultures to evaluate the effects of SUC against 1-methyl-4-phenylpyridinium (MPP+) toxicity in vitro. C57BL/6 mice were treated with SUC (10 mg/kg/day, intragastric (i.g.)) for 30 days, and thereafter, animals received MPTP infusion (1 mg/nostril) and SUC treatment continued for additional 15 days. MPTP-infused animals displayed significant non motor symptoms including olfactory and short-term memory deficits evaluated in the olfactory discrimination, social recognition, and water maze tasks. These behavioral impairments were accompanied by inhibition of mitochondrial NADH dehydrogenase activity (complex I), as well as significant decrease of TH and dopamine transporter (DAT) immunoreactivity in the substantia nigra pars compacta and striatum. Although SUC treatment did not rescue NADH dehydrogenase activity inhibition, it was able to blunt MPTP-induced behavioral impairments and prevented the decrease in TH and DAT immunoreactivities in substantia nigra (SN) and striatum. SUC also suppressed striatal astroglial activation and increased interleukin-6 levels in MPTP-intoxicated mice. Furthermore, SUC significantly prevented the loss of TH+ neurons induced by MPP+ in primary mesencephalic cultures. These results provide new evidence that SUC treatment counteracts early non-motor symptoms and neurodegeneration/neuroinflammation in the nigrostriatal pathway induced by intranasal MPTP administration in mice by modulating events downstream to the mitochondrial NADH dehydrogenase inhibition. PMID- 26852413 TI - Rapid addition of unlabeled silent solubility tags to proteins using a new substrate-fused sortase reagent. AB - Many proteins can't be studied using solution NMR methods because they have limited solubility. To overcome this problem, recalcitrant proteins can be fused to a more soluble protein that functions as a solubility tag. However, signals arising from the solubility tag hinder data analysis because they increase spectral complexity. We report a new method to rapidly and efficiently add a non isotopically labeled Small Ubiquitin-like Modifier protein (SUMO) solubility tag to an isotopically labeled protein. The method makes use of a newly developed SUMO-Sortase tagging reagent in which SUMO and the Sortase A (SrtA) enzyme are present within the same polypeptide. The SUMO-Sortase reagent rapidly attaches SUMO to any protein that contains the sequence LPXTG at its C-terminus. It modifies proteins at least 15-times faster than previously described approaches, and does not require active dialysis or centrifugation during the reaction to increase product yields. In addition, silently tagged proteins are readily purified using the well-established SUMO expression and purification system. The utility of the SUMO-Sortase tagging reagent is demonstrated using PhoP and green fluorescent proteins, which are ~90% modified with SUMO at room temperature within four hours. SrtA is widely used as a tool to construct bioconjugates. Significant rate enhancements in these procedures may also be achieved by fusing the sortase enzyme to its nucleophile substrate. PMID- 26852412 TI - Exceptions to the rule of informed consent for research with an intervention. AB - BACKGROUND: In specific situations it may be necessary to make an exception to the general rule of informed consent for scientific research with an intervention. Earlier reviews only described subsets of arguments for exceptions to waive consent. METHODS: Here, we provide a more extensive literature review of possible exceptions to the rule of informed consent and the accompanying arguments based on literature from 1997 onwards, using both Pubmed and PsycINFO in our search strategy. RESULTS: We identified three main categories of arguments for the acceptability of a consent waiver: data validity and quality, major practical problems, and distress or confusion of participants. Approval by a medical ethical review board always needs to be obtained. Further, we provide examples of specific conditions under which consent waiving might be allowed, such as additional privacy protection measures. CONCLUSIONS: The reasons legitimized by the authors of the papers in this overview can be used by researchers to form their own opinion about requesting an exception to the rule of informed consent for their own study. Importantly, rules and guidelines applicable in their country, institute and research field should be followed. Moreover, researchers should also take the conditions under which they feel an exception is legitimized under consideration. After discussions with relevant stakeholders, a formal request should be sent to an IRB. PMID- 26852415 TI - Latent trait testosterone among 18-24 year olds: Methodological considerations and risk associations. AB - The study investigated the relationship between latent trait testosterone (LTT) and risk-taking among 126 youth (M age=21.34years; 56% female; 52% African American). Latent state-trait (LST) modeling isolates observed variance of samples via their correlations into (1) a latent trait testosterone (LTT) factor capturing individual differences, and (2) a component of state testosterone factor (LST) capturing state-specific situational or environmental influences and random error variances. Participants provided four laboratory (20min apart) and four home (waking, 20-min post-waking, noon, evening) salivary samples (later assayed for testosterone). Participants reported risk-taking tendencies and behaviors via an Audio Computer Assisted Self-Interview. Behavioral risk was measured using the Balloon Analog Risk Task. Results revealed: (1) LTT model invariance (operated similarly) for females and males; (2) LTT accounted for 18 89% (home samples) and 61-95% (lab samples) of the variance in testosterone levels, and (3) LTT was associated with risk-seeking behaviors and the strength of this association was similar across males and females. LST Modeling has potential to advance our understanding of testosterone-behavior associations to new limits by estimating stable trait-like components of the variance in testosterone levels. PMID- 26852414 TI - Direct 13C-detected NMR experiments for mapping and characterization of hydrogen bonds in RNA. AB - In RNA secondary structure determination, it is essential to determine whether a nucleotide is base-paired and not. Base-pairing of nucleotides is mediated by hydrogen bonds. The NMR characterization of hydrogen bonds relies on experiments correlating the NMR resonances of exchangeable protons and can be best performed for structured parts of the RNA, where labile hydrogen atoms are protected from solvent exchange. Functionally important regions in RNA, however, frequently reveal increased dynamic disorder which often leads to NMR signals of exchangeable protons that are broadened beyond (1)H detection. Here, we develop (13)C direct detected experiments to observe all nucleotides in RNA irrespective of whether they are involved in hydrogen bonds or not. Exploiting the self decoupling of scalar couplings due to the exchange process, the hydrogen bonding behavior of the hydrogen bond donor of each individual nucleotide can be determined. Furthermore, the adaption of HNN-COSY experiments for (13)C direct detection allows correlations of donor-acceptor pairs and the localization of hydrogen-bond acceptor nucleotides. The proposed (13)C direct detected experiments therefore provide information about molecular sites not amenable by conventional proton-detected methods. Such information makes the RNA secondary structure determination by NMR more accurate and helps to validate secondary structure predictions based on bioinformatics. PMID- 26852416 TI - Multidimensional J-driven NMR correlations by single-scan offset-encoded recoupling. AB - Two-dimensional (2D) correlations between bonded heteroatoms, lie at the cornerstone of many uses given to contemporary nuclear magnetic resonance (NMR). Improving the efficiency with which these correlations are established is an important topic in modern NMR, with potential applications in rapid chemical analysis and dynamic biophysical studies. Alternatives have been developed over the last decade to speed up these experiments, based among others on reducing the number of data points that need to be sampled, and/or shortening the inter-scan delays. Approaches have also been proposed to forfeit multi-scan schemes altogether, and complete full 2D correlations in a single shot. Here we explore and discuss a new alternative enabling the collection of such very fast - in principle, single-scan - acquisitions of 2D heteronuclear correlations among bonded species, which operates on the basis of a partial reintroduction of J couplings. Similar approaches had been proposed in the past based on collecting coupled spectra for arrays of off-resonance decoupling values; the proposal that is here introduced operates on the basis of suitably incorporating frequency swept pulses, into spin-echo sequences. Thanks to the offset-dependent amplitude modulations of the in- and anti-phase components that such sequences impart, chemical shifts of coupled but otherwise unobserved nuclear species, can be extracted from the relative intensities and phases of J-coupled multiplets observed in one-dimensional acquisitions. A description of the steps needed to implement this rapid acquisition approach in a quantitative fashion, as well as applications of the ensuing sequences, are presented. PMID- 26852417 TI - Nonadiabatic exchange dynamics during adiabatic frequency sweeps. AB - A Bloch equation analysis that includes relaxation and exchange effects during an adiabatic frequency swept pulse is presented. For a large class of sweeps, relaxation can be incorporated using simple first order perturbation theory. For anisochronous exchange, new expressions are derived for exchange augmented rotating frame relaxation. For isochronous exchange between sites with distinct relaxation rate constants outside the extreme narrowing limit, simple criteria for adiabatic exchange are derived and demonstrate that frequency sweeps commonly in use may not be adiabatic with regard to exchange unless the exchange rates are much larger than the relaxation rates. Otherwise, accurate assessment of the sensitivity to exchange dynamics will require numerical integration of the rate equations. Examples of this situation are given for experimentally relevant parameters believed to hold for in-vivo tissue. These results are of significance in the study of exchange induced contrast in magnetic resonance imaging. PMID- 26852418 TI - Intra-coil interactions in split gradient coils in a hybrid MRI-LINAC system. AB - An MRI-LINAC system combines a magnetic resonance imaging (MRI) system with a medical linear accelerator (LINAC) to provide image-guided radiotherapy for targeting tumors in real-time. In an MRI-LINAC system, a set of split gradient coils is employed to produce orthogonal gradient fields for spatial signal encoding. Owing to this unconventional gradient configuration, eddy currents induced by switching gradient coils on and off may be of particular concern. It is expected that strong intra-coil interactions in the set will be present due to the constrained return paths, leading to potential degradation of the gradient field linearity and image distortion. In this study, a series of gradient coils with different track widths have been designed and analyzed to investigate the electromagnetic interactions between coils in a split gradient set. A driving current, with frequencies from 100 Hz to 10 kHz, was applied to study the inductive coupling effects with respect to conductor geometry and operating frequency. It was found that the eddy currents induced in the un-energized coils (hereby-referred to as passive coils) positively correlated with track width and frequency. The magnetic field induced by the eddy currents in the passive coils with wide tracks was several times larger than that induced by eddy currents in the cold shield of cryostat. The power loss in the passive coils increased with the track width. Therefore, intra-coil interactions should be included in the coil design and analysis process. PMID- 26852419 TI - Doctors Who Integrate Spirituality and CAM in the Clinic: The Puerto Rican Case. AB - This article describes Puerto Rican physicians' personal and clinical utilization of complementary and alternative medicines (CAM), its effects, and use as they identified as either Spiritist, spiritual or religious. Semi-structured interviews were conducted with 74 doctors in Puerto Rico. Major themes and relationships among them were charted using the qualitative data analysis program MAXQDA, open coding and grounded theory. Thirty-one doctors spoke of CAM and its use as related to their spiritual or religious perspectives. Spiritual or Spiritist doctors were more inclined than religious doctors to utilize CAM. Seeking closer relationships with patients was related to a spiritually oriented goal of healing (as distinct from curing) as a reason to recommend CAM. PMID- 26852420 TI - Low-dose human chorionic gonadotropin alone can complete follicle maturity: successful application to modified natural cycle in vitro fertilization. AB - OBJECTIVE: To investigate the feasibility of utilizing low-dose hCG alone to complete follicle maturity in a natural cycle, without the need for antecedent exogenous FSH stimulation. DESIGN: Case series. SETTING: Academic fertility program. PATIENT(S): Normally ovulatory women with infertility thought to be predominantly due to male factor. INTERVENTION(S): Modified natural IVF cycles were conducted as follows: natural ovulatory cycles were monitored with serial ultrasound examinations and serum E2 determinations. When the lead follicle reached preovulatory status according to cycle day, ultrasound, and E2 levels, 0.25 mg of the GnRH antagonist ganirelix acetate was administered along with 200 IU of hCG. These medications were repeated daily for 2 to 3 days with further serial monitoring. A trigger dose of 10,000 IU of hCG was followed by follicle aspiration, IVF, and ET in a standard manner. MAIN OUTCOME MEASURE(S): Follicle maturity, live births, documentation of the feasibility of this new approach. RESULT(S): In all cases, E2 levels rose and the dominant follicle continued to increase in size in response to low-dose hCG after GnRH antagonist administration. Follicle aspiration yielded one or more mature oocytes. In vitro fertilization and ET resulted in live births. CONCLUSION(S): Low-dose hCG can be used to complete follicle maturity in a natural cycle without the need for antecedent exogenous FSH stimulation. This finding may have strong clinical utility in modified natural cycle IVF. PMID- 26852421 TI - Cardiovascular disease risk in first-degree relatives of women with polycystic ovary syndrome. AB - OBJECTIVE: To assess the risk of cardiovascular disease (CVD) in the parents of polycystic ovary syndrome (PCOS) patients using carotid intima medial thickness (CIMT) and brachial artery flow-mediated dilatation (FMD). DESIGN: Hospital-based case-control study. SETTING: Endocrine clinic of a medical institute in India. PATIENT(S): Case group of 41 fathers and 45 mothers of PCOS patients (confirmed by Rotterdam's criteria) compared with 42 men and 44 women matched by age, sex and body mass index (BMI) as controls. INTERVENTION(S): CVD risk in parents of PCOS patients assessed via CIMT and FMD then correlated with various clinical and metabolic parameters. MAIN OUTCOME MEASURE(S): Differences in CIMT and FMD between parents and controls. RESULT(S): The CIMT was higher [0.6 (0.54-0.8) vs. 0.5 (0.45-0.55) mm] and brachial artery FMD was lower [11.9% (6.9%-16.2%) vs. 16.7% (13.5%-22.6%)] in the parents of PCOS patients as compared with the controls. Systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol, and fasting and 2-hour plasma glucose were higher in the parents of the PCOS patients. The prevalence of CVD risk factors such as systemic hypertension, diabetes mellitus, abdominal obesity, the metabolic syndrome, and a family history of coronary artery disease in first-degree relatives was also higher in the parents of PCOS patients. The prevalence of diabetes was higher in the fathers of PCOS women, but other cardiovascular disease risk factors, CIMT, and FMD were comparable among the mothers. CONCLUSION(S): The parents of PCOS patients have an increased CVD risk as evidenced by increased CIMT and low FMD. PMID- 26852422 TI - Hexokinase is a key regulator of energy metabolism and ROS activity in insect lifespan extension. AB - Developmental arrest (diapause) is a 'non-aging' state that is similar to the Caenorhabditis elegans dauer stage and Drosophila lifespan extension. Diapause results in low metabolic activity and a profound extension of insect lifespan. Here, we cloned the Helicoverpa armigera Hexokinase (HK) gene, a gene that is critical for the developmental arrest of this species. HK expression and activity levels were significantly increased in nondiapause-destined pupae compared with those of diapause-destined pupae. Downregulation of HK activity reduced cell viability and delayed pupal development by reducing metabolic activity and increasing ROS activity, which suggests that HK is a key regulator of insect development. We then identified the transcription factors Har-CREB, -c-Myc, and POU as specifically binding the Har-HK promoter and regulating its activity. Intriguingly, Har-POU and -c-Myc are specific transcription factors for HK expression, whereas Har-CREB is nonspecific. Furthermore, Har-POU and -c-Myc could respond to ecdysone, which is an upstream hormone. Therefore, low ecdysone levels in diapause-destined individuals lead to low Har-POU and -c-Myc expression levels, ultimately repressing Har-HK expression and inducing entry into diapause or lifespan extension. PMID- 26852423 TI - Exploration of the affordances of mobile devices in integrating theory and clinical practice in an undergraduate nursing programme. AB - BACKGROUND: Promoting the quality and effectiveness of nursing education is an important factor, given the increased demand for nursing professionals. It is important to establish learning environments that provide personalised guidance and feedback to students about their practical skills and application of their theoretical knowledge. OBJECTIVE: To explore and describe the knowledge and points of view of students and educators about introduction of new technologies into an undergraduate nursing programme. METHOD: The qualitative design used Tesch's (1990) steps of descriptive data analysis to complete thematic analysis of the data collected in focus group discussions (FGDs) and individual interviews to identify themes. RESULTS: Themes identified from the students' FGDs and individual interviews included: mobile devices as a communication tool; email, WhatsApp and Facebook as methods of communication; WhatsApp as a method of communication; nurses as role-models in the clinical setting; setting personal boundaries; and impact of mobile devices in clinical practice on professionalism. Themes identified from the FGD, individual interviews and a discussion session held with educators included: peer learning via mobile devices; email, WhatsApp and Facebook as methods of communication; the mobile device as a positive learning method; students need practical guidance; and ethical concerns in clinical facilities about Internet access and use of mobile devices. CONCLUSION: The research project established an understanding of the knowledge and points of view of students and educators regarding introduction of new technologies into an undergraduate nursing programme with the aim of enhancing integration of theory and clinical practice through use of mobile devices. PMID- 26852424 TI - Student nurses' perceptions of guidance and support in rural hospitals. AB - BACKGROUND: Clinical guidance and support of nursing students in rural hospitals is a challenge for novice nurses, who rotate amongst accredited hospitals throughout the province for clinical exposure, and find themselves in an unfamiliar environment. Theory learned at the training college is integrated with clinical exposure at hospitals and supplemented through teaching by hospital staff. Nursing students complain about lack of support and guidance from professional nurses within the hospital, some feeling restricted in execution of their nursing tasks by professional nurses and other staff. Students perceived negative attitudes from clinical staff, a lack of clinical resources, inadequate learning opportunities and a lack of support and mentoring during their clinical exposure. OBJECTIVES: This article describes perceptions of guidance and support of nursing students by professional nurses in a rural hospital and suggests guidelines for clinical guidance and support of nursing students. METHOD: A qualitative, explorative, descriptive and contextual design was used. Two focus group interviews were employed to collect data from a sample drawn from level II nursing students from one training college in Limpopo Province, South Africa, on different days (n = 13; n = 10). Qualitative content analysis was used to analyse data. RESULTS: Three themes (mutual distrust and disrespect, hospital environment, and clinical guidance and support) and subthemes (student behaviour and staff behaviour) emerged. CONCLUSION: Failure to support and guide nursing students professionally may lead to high turnover and absenteeism, resulting in students' refusal to be allocated to a rural hospital for clinical exposure. Proposed guidelines have been formulated for clinical guidance and support of nursing students at the selected rural hospital. The college and hospital management should foster collaboration between the college tutors and professional nurses to ensure adequate guidance and support of nursing students. PMID- 26852425 TI - Views of professional nurses regarding low tuberculosis cure rate in Greater Giyani Municipality, Limpopo Province. AB - BACKGROUND: Management of patients suffering from tuberculosis (TB) after discharge from hospital plays a critical role in the cure rate of TB. Despite interventions developed by the World Health Organization (WHO) to improve the cure rate, TB remains a worldwide health problem. OBJECTIVE: The purpose of the study was to explore and describe the views of professional nurses regarding the low TB cure rate in primary healthcare facilities of Greater Giyani Municipality in Limpopo Province, South Africa, with the aim of determining strategies that can be used to improve this low rate. METHOD: This study was qualitative, exploratory, descriptive and contextual in nature. The population consisted of professional nurses working in primary healthcare facilities within Greater Giyani Municipality, which has a TB cure rate below the national target of 85%. Data gathering was through individual face-to-face interviews using an interview guide. Open-coding was used to analyse the data in this study. RESULTS: The theme that emerged from data was 'factors contributing to low TB cure rate'. This theme was supported by the following sub-themes: poor referral system, lack of knowledge about TB and its treatment, stigma attached to TB, and cultural and religious beliefs. The professional nurses suggested counselling of TB patients upon diagnosis, advice about patients' responsibilities and the involvement of family members. CONCLUSION: The involvement of community stakeholders in TB prevention, health promotion and education activities devoted to disease spread and cure is vital so that the stigma attached to TB can be eliminated. TB education and awareness programmes should be included in the curriculum of primary schools. PMID- 26852426 TI - Using a simulated patient to transfer patient-centred skills from simulated practice to real patients in practice. AB - BACKGROUND: Simulation in healthcare education is common practice. Although this teaching strategy increases patient safety, it is not proven to enhance patient centred care in practice. Simulated patients are used to teach communication skills and to contribute to the authenticity of the simulation. Could this enhanced authenticity help bridge the gap from simulated practice to practice with live patients where patient-centredness is of crucial importance? OBJECTIVE: This study's objective was to determine whether students who acquired a skill in simulation using a simulated patient displayed more patient-centredness in practice than students who used a mannikin. METHOD: A pre-experimental, post-test only design with a comparison group was used. The population sample comprised all second-year B.Cur. students (N = 36) at a tertiary institution, who were divided into two cohorts. Cohort 1 was trained to administer an intramuscular injection using a simulated patient with a strap-on injectable device, whilst cohort 2 used an injection model. All participants were assessed on their procedural skills as well as patient-centred care whilst administering an injection to a patient in hospital. A comparison was made of mean scores for patient-centred care rendered by the two cohorts. RESULTS: Fisher's exact test revealed that the mean score for patient-centredness of cohort 1 (88%) was significantly higher (p = < 0.001) than that of cohort 2 (74%). CONCLUSION: Using a simulated patient to teach administration of an intramuscular injection enhanced students' patient centredness when performing the procedure in practice. Recommendations include making use of a bigger sample and including a pre-test the next time research of this nature is carried out. PMID- 26852427 TI - Factors influencing treatment outcomes in tuberculosis patients in Limpopo Province, South Africa, from 2006 to 2010: A retrospective study. AB - BACKGROUND: South Africa has a high burden of tuberculosis (TB), with high human immunodeficiency virus (HIV)-TB co-infection rates and the emergence of multidrugresistant TB. OBJECTIVES: To describe treatment outcomes and factors influencing outcomes amongst pulmonary TB (PTB) patients in the Limpopo Province. METHOD: A retrospective review was conducted of data on the provincial electronic TB register (ETR.net) for the years 2006 to 2010 (inclusive), and a random sample of 1200 records was selected for further analysis. The Chi square test was used to examine the influence of age, gender, health facility level, diagnostic category and treatment regimen on treatment outcomes. RESULTS: Overall 90 617 (54.6% male) PTB patients were registered between 2006 and 2010. Of the sampled 1200 TB cases, 72.6% were in persons aged 22 to 55 years and 86.2% were new cases. The TB mortality rate was 13.6% (much higher than the World Health Organization target of 3%), whilst the default rate was 9.8%. There was a strong association between age (P < 0.001), diagnostic category (P < 0.001), treatment regimen (P < 0.001), and health facility level (P < 0.001) and treatment outcome. Those aged 22-55, and 56-74 years were more likely to die (P < 0.05). Poor treatment outcomes were also associated with initial treatment failure, receiving treatment at hospital and treatment regimen II. CONCLUSION: The poor TB treatment outcomes in Limpopo, characterised by a high mortality and default rates, call for strengthening of the TB control programme, which should include integration of HIV and/or AIDS and TB services. PMID- 26852428 TI - Cardiopulmonary resuscitation knowledge and skills of registered nurses in Botswana. AB - BACKGROUND: In Botswana nurses provide most health care in the primary, secondary and tertiary level clinics and hospitals. Trauma and medical emergencies are on the increase, and nurses should have cardiopulmonary resuscitation (CPR) knowledge and skills in order to be able to implement effective interventions in cardiac arrest situations. OBJECTIVE: The objective of this descriptive study was to assess registered nurses' CPR knowledge and skills. METHOD: A pre-test, intervention and re-test time-series research design was adopted, and data were collected from 102 nurses from the 2 referral hospitals in Botswana. A multiple choice questionnaire and checklist were used to collect data. RESULTS: All nurses failed the pre-test. Their knowledge and skills improved after training, but deteriorated over the three months until the post-test was conducted. CONCLUSION: The significantly low levels of registered nurses' CPR skills in Botswana should be addressed by instituting country-wide CPR training and regular refresher courses PMID- 26852429 TI - Schistosomiasis: number of people treated worldwide in 2014. PMID- 26852430 TI - Tribute to Victor Frankel, M.D., Ph.D., K.N.O. On the Occasion of his 90th Birthday at the 2015 Sir Robert Jones Professorship Meeting--NYU Hospital for Joint Diseases, May 15, 2015. PMID- 26852431 TI - In Memoriam Benjamin Shaffer, M.D. PMID- 26852432 TI - A Few Final Thoughts. PMID- 26852433 TI - CT Utilization for Pediatric Orthopedic Trauma. AB - BACKGROUND: The use of computed tomography (CT) scanning in trauma has tripled in the past decade in adults and children alike. There is growing concern about the long-term risks of radiation delivery in childhood. There is little information in the literature on radiation exposure during extremity CT in children. This study evaluated the radiation dose and geographic bodily exposure to the child/adolescent during extremity CT. METHODS: A retrospective review of 163 patients (girls aged 0.5-19 years and boys aged 3.1-19 years) who sustained an orthopedic extremity injury that required a CT scan in 2012 was performed. Data collected included sex, age, height, weight, body mass index (BMI), joint, upper extremity position, body position, scout start, scout end, CTDIvol (mGy), and dose length product (CTDLP (mGy-cm)). RESULTS: Lower extremity scans were more frequent (124/163, 76 percent) and had higher radiation doses overall. Only the elbow varied for upper extermity positioning. Five of nine were on the side of body with a corresponding 66 percent lower mean radiation dose. All lower extremity scans were in the supine position. Scout CT start and end varied among all joints except for femur to tibia. CONCLUSIONS: Lower extremity CT scans had the highest radiation doses. Variability in positioning and delineation of scout contributed to variation in radiation exposure of extremity and adjacent body area. Improved localization and consistent positioning can effectively lower radiation exposure in children undergoing extremity CT scan. PMID- 26852434 TI - Aortocoronary Saphenous Vein Graft Aneurysm with Fistula to the Right Atrium: Percutaneous Management of Surgical Complication. AB - Aneurysmal dilatation of aortocoronary saphenous vein grafts (SVG) is a rare but known complication after coronary artery bypass grafting (CABG). They are most commonly found incidentally, although some may present with unstable angina or myocardial infarction (MI). Rarely, these aneurysms can develop into fistulas to the neighboring cardiac chambers. We report the case of a 66-year old woman with a history of CABG in 1996 with a left internal mammary artery (LIMA) graft to the left anterior descending and a SVG to distal right coronary artery presenting with non-ST segment elevation myocardial infarction (NSTEMI) complicated with congestive heart failure. Selective Coronary and Graft angiography showed an aneurysm in the mid SVG with a fistula into the right atrium (RA) resulting in a significant left to right shunt. The significant left to right shunt diverted blood flow from right coronary artery territory resulting in recurrent ischemia and angina and introduced a significant volume overload on the right ventricle resulting in over heart failure. Secondary to the course of LIMA graft along the sternum, surgery was not an option. Secondary to continued symptoms percutaneous intervention was performed with placement of two 6.0 x 50 mm Viabahn self expanding covered stent with aggressive post-dilation resulting in successful closure with no residual flow. Percutaneous intervention is shown to be an effective approach to manage both aortocoronary fistula and grafts ruptures and is associated with better outcomes than surgical and conservative options. To the best of our knowledge, this is the first reported case of a successful closure of fistulous communication of a SVG aneurysm to the RA utilizing multiple peripheral covered stents. PMID- 26852435 TI - PATTERN OF INTERSTITIAL LUNG DISEASE AS SEEN BY HIGH RESOLUTION COMPUTERISED TOMOGRAPHY. AB - BACKGROUND: Diffuse lung diseases constitute a major cause of morbidity and mortality worldwide. High Resolution Computed Tomography (HRCT) is the recommended imaging technique in the diagnosis, assessment and followup of these diseases. OBJECTIVES: To describe the pattern of HRCT findings in patients with suspected interstitial lung disease. SETTING: Kenyatta National Hospital (KNH), Nairobi Hospital and MP Shah Hospital; all situated in Nairobi, during the period February to August 2010. SUBJECTS: One hundred and one patients sent for HRCT in the six month study period. RESULTS: A total of 101 patients were recruited with age range 18 to 100 years, with a mean age of 53.6 (SD 19.7) years and a median age of 54 years. The male-female ratio was 1.2:1. Cough [80.2% (n = 81)] was the most common presenting complaint followed by dyspnoea (53.5%, n = 53) and chest pain [24.8% (n = 25)]. Overall, the predominant pattern of involvement on chest HRCT was reticular pattern seen in 56.1% (n = 82) of patients, followed by honey comb pattern (37.8%, n = 82). CONCLUSION: The study demonstrated marked lung parenchymal destruction in most cases; a poor prognostic indicator which could have been due to delayed referral. HRCT has a high pick up rate of subtle parenchymal lung lesions as well as defining the lesions and their distribution compared to plain chest radiography. This is important in narrowing the differential diagnosis as well as for pre-biopsy planning. The diagnosis of ILD requires a multidisciplinary approach including a detailed clinical history, physical findings, and laboratory investigations, radiological and histological assessment. PMID- 26852436 TI - EFFECT OF PRE-OPERATIVE SUB-LINGUAL MISOPROSTOL VERSUS INTRAVENOUS OXYTOCIN ON CAESAREAN OPERATION BLOOD LOSS. AB - BACKGROUND: Caesarean operation remains the most common abdominal surgery in women and has immense benefits to both mother and baby when employed. Haemorrhage, however, remains the greatest challenge associated with its outcome. OBJECTIVE: To compare the effectiveness of pre-operative sub-lingual misoprostol with intravenous oxytocin administered after delivery of the neonate in minimising blood loss at Caesarean operation. DESIGN: A prospective study. RESULTS: The mean blood loss was significantly lower in misoprostol group compared to oxytocin group (517.32mls versus 621.22mls; p = 0.005). The drop in haematocrit was significantly lower in misoprostol group than the oxytocin group, (400 MUg-misoprostol versus oxytocin: 1.88 versus 3.04; p = 0.0001). Side effects of chills, shivering and pyrexia were noted more with the use of misoprostol. CONCLUSION: Pre-operative sub-lingual misoprostol is more effective than intravenous infusion of oxytocin in reducing blood loss at Caesarean section operation. However, occurrence of transient side effects of chills, shivering and pyrexia were noted more with use of misoprostol. PMID- 26852437 TI - COMMUNITY ACQUIRED PNEUMONIA AMONG CHILDREN ADMITTED IN A TERTIARY HOSPITAL: THE BURDEN AND RELATED FACTORS. AB - OBJECTIVE: To find out the hospital burden of pneumonia and preventable factors associated with the disease. DESIGN: Prospective cross sectional study. SETTING: The paediatric ward of Moi Teaching and Referral Hospital in Western Kenya. SUBJECTS: All the children admitted to the paediatric wards and found to have clinical features consistent with pneumonia. RESULTS: One thousand eight hundred and eighty two children were included in the study out of whom pneumonia was responsible for 13.23% and 5.5% of all deaths. Degree of severity was used to classify patients into mild pneumonia, severe pneumonia and very severe pneumonia each group comprised 12%, 70% and 18% respectively. Parents in age group 21 to 25 years (OR 2, CI 1.07 - 3.63) and use of firewood /charcoal (OR 4.23, CI 3.9 - 4.6) were risk factors for mild pneumonia. Unemployment (OR 2.7, CI 2 - 3.2), age group 21 to 25 years (OR 4, CI 1.2 - 6.4) and use of firewood/charcoal (OR 1.1, CI 1.02 - 1.26) were risk factors for severe pneumonia. CONCLUSION: Pneumonia accounted for less number of admitted children compared to previous study. Use of firewood or charcoal as source of fuel and mothers in age group 21 - 25 years were independent risk factors for mild pneumonia and severe pneumonia. PMID- 26852438 TI - MAXILLOFACIAL SOFT TISSUE INJURIES IN NAIROBI, KENYA. AB - OBJECTIVES: To determine the aetiological factors and pattern of occurrence of maxillofacial soft tissue injuries (MF-STIs) presenting at a Kenyan National Referral Hospital in Nairobi. DESIGN: A cross-sectional study. SETTINGS: The accident and emergency department of the Kenyatta National Hospital (KNH) between September 2009 and December 2009. SUBJECTS: Four hundred and twenty two patients treated for MF-STIs. RESULTS: The male to female ratio was 3.3:1. Motor vehicle accidents (MVA) were the leading cause of MF-STIs (44.6%) followed by interpersonal violence (IPV) (39.1%). MVA (50.0%) was the leading cause of MF STIs in the less than 12-year-olds while falls from heights (58.3%) was the leading cause in under five-year-olds. IPV (48.1%) was the leading cause of facial fractures. There were no skeletal fractures observed in the under five year-olds. Head injury (36%) and fractures of the long bones (52%) were the most common associated injuries. CONCLUSION: The leading causes of MF-STIs apparently differ from those of skeletal fractures. PMID- 26852439 TI - FEMALE SEXUAL DYSFUNTION AND GYNAECOLOGICAL PRACTICE: REPORT OF SIX CASES. AB - Sexuality is a complex phenomenon, yet an essential part of a healthy life, influenced by biological, psychological and socio-economic factors. Current re conceptualisation of women's sexual response acknowledges that they have many reasons for engaging in sex beyond sexual desire. Women are increasingly becoming aware of their sexuality and demand sexual fulfilment more than ever before and when that is not realised there may be personal distress. Female sexual dysfunction is prevalent in all populations and cultures globally. However, very few women seek medical help due to belief that the problem is not serious, challenges with access to or affordability of care and lack of awareness of available treatments. It's also infrequently diagnosed, due to lack of awareness among health care providers. Case scenarios on female sexual dysfunction managed by the author are presented with the aim of raising awareness among health professionals. Possible strategies to address the problems are proposed. PMID- 26852440 TI - MATERNAL HYPOTENSION AND NEONATAL ACIDAEMIA DURING CAESEREAN DELIVERY UNDER SPINAL ANAESTHESIA. AB - OBJECTIVES: To determine the incidence of neonatal acidaemia following delivery through caesarean section under spinal anaesthesia and determine the prevalence of maternal hypotension during Caesarean section under spinal anaesthesia and its correlation with neonatal acidaemia. DESIGN: Prospective observational study. SETTING: Kenyatta National Hospital (KNH), Nairobi, Kenya. SUBJECTS: One hundred and seventy-two ASA I and II consecutive term patients undergoing elective Caesarean section under spinal anaesthesia. RESULTS: Forty three babies (27.2%) were born with neonatal acidaemia, defined as umbilical arterial blood pH 7.2. There was, however, no significant difference in the five minute Apgar scores between the acidotic and non-acidotic neonates. Twenty eight patients (17.7%) developed maternal hypotension (systolic Blood Pressure less than 100mmHg). The hypotension was readily corrected within two minutes (mean of 1.43 minutes) of onset using vasopressors and boluses of intravenous fluids. CONCLUSIONS: A short period (< 2 minutes) mean of 1.43 minutes of maternal hypotension has no significant effect on the neonate as assessed by five minute Apgar Scores. Similarly, neonatal acidaemia following Caesarean delivery under spinal anaesthesia does not seem to have any short-term effects on neonatal well-being. PMID- 26852441 TI - PNEUMONIA COMPLICATED BY CONGESTIVE HEART FAILURE IN NIGERIAN CHILDREN. AB - OBJECTIVE: To evaluate heart failure in patients with pneumonia. SETTING: The paediatric wards of a tertiary hospital in Nigeria. SUBJECTS: One hundred and four patients were studied. RESULTS: The mean age was 10.3 +/- 11.0 months and 53(51.0%) were males. Of the 104, 41(39.4%) also had Congestive Cardiac Failure (CCF). All 41(100%) patients with CCF compared to 38 of 63 (60.3%) with pneumonia only had cardiomegaly (p = 0.0001). Ten of 61(16.4%) patients with chest X ray had a cardiothoracic ratio (CTR) > 60%. Ten children had dilated ventricular chambers, eight (80.0%) had dilated inferior vena cavae and seven (70%) had myocarditis. CONCLUSION: The prevalence of CCF complicating pneumonia was high. Tender hepatomegaly, increased CTR and myocarditis were pointers to CCF complicating pneumonia. PMID- 26852442 TI - APPENDICITIS IN UNIVERSITY OF PORT HARCOURT TEACHING HOSPITAL, NIGERIA. AB - Background: Acute appendicitisis themost common cause of acute abdomen worldwide with increasing incidence in developing countries. The diagnosis is mainly clinical and wound infection remains the most common post-operative complication. OBJECTIVE: To determine the pattern of presentation of acute appendicitis. DESIGN: Hospital based retrospective study. SETTING: Department of Surgery, University of Port Harcourt Teaching Hospital, Nigeria. SUBJECTS: Patients with histologically confirmed acute appendicitis. RESULTS: A total of 130 patients who had appendicectomy for acute appendicitis were included in the study. There were 62 males and 68 females (M:F1:1.1). Their ages ranged from 14 to 67 years with a peak age incidence of 21-30 years. The highest incidence was in the month of July while the lowest was in February. All the patients presented with right iliac fossa pain and tenderness. Post-operative complication rate was 10% and wound infection was the most common (7.7%). CONCLUSION: The presentation of acute appendicitis in UPTH is similar to that in other parts of the West African sub region but with a slight female preponderance in our centre. Early diagnosis and prompt surgical intervention is the key to successful management. PMID- 26852443 TI - CAUSES OF SUDDEN NATURAL DEATH: A MEDICO-LEGAL AUTOPSY STUDY OF MEDICAL CASES IN AN AFRICAN REFERRAL CENTRE. AB - OBJECTIVE: To evaluate and characterise the causes of sudden natural deaths (SNDs) that occurred in medical cases in an African referral centre. DESIGN: A descriptive retrospective study. SETTING: University of Benin Teaching Hospital, between January 2005 and December 2011. SUBJECTS: Autopsy reports of 626 cases that were referred to the coroner. RESULTS: A total of 626 cases of SNDswere identified representing 30.3% of all autopsies performed within the period. There were 390 (62.3%) males and 236 (37.7%) females with a M:F ratio of 1.7:1. The age range of the cases was 19-105 years with a mean age of 51 +/- 17 years. The modal age group was 40-49 years which accounted for 19.8% of the cases, and most of the cases (56.8%) were seen in the 30-59 year age groups. In majority of cases (39.3%), the cause of death was related to the cardio-vascular system-principally death due to complications of hypertension which was seen in 88.2% of the cardio vascular system diseases. Immune/infectious diseases (mainly AIDS), gastro intestinal/hepatic lesions and respiratory diseases were seen in 15.2, 14.1 and 12.5% of cases respectively. SNDs due to malignant neoplasms were not a common finding as they occurred in 5.1% of cases. CONCLUSION: This study shows that with the increasing, modernisation of our lifestyle and dietary habits, cardio vascular system diseases-particularly complications of hypertension have become the leading cause of sudden natural death in our environment. PMID- 26852444 TI - PERCEPTION OF NIGERIAN ANAESTHETISTS ON INTRA-OPERATIVE DEATH. AB - BACKGROUND: Intra-operative death is an unusual devastating occurrence in anaesthetic practice, and it is of serious concern when it happens. OBJECTIVES: To assess the causes, the effects and the perception of Nigerian anaesthetists to intra-operative death. DESIGN: A cross-sectional and questionnaire-based study. SETTING: Five University Teaching Hospitals in South-Western Nigeria. SUBJECTS: Nurse anaesthetists, resident doctors in anaesthesia and consultant anaesthetists. RESULTS: One hundred and five anaesthetists participated in the study (72.9% response rate). Seventy seven (73.3%) of the respondents had experienced an intra-operative death with most of them having five or more years of experience (p = 0.0001). Majority 53 (68.8%) of the respondents felt that the deaths were avoidable, and most deaths occurred mainly during emergency surgery (96.1%). Forty three (55.8%) of them were psychologically disturbed, fifty six (53.3%) respondents were of the opinion that it is reasonable for the anaesthetists involved not to take partin further surgery for that day. Sixty (57.1%) respondents considered discussion at mortality meeting as appropriate after an intra-operative death. CONCLUSION: This study showed that most anaesthetists would want those involved in the intra-operative death not to take part in further surgery for that day. Adequate preventive measures should be put in place with departmental or institutional policies on what to do after such events. PMID- 26852445 TI - RISK FACTORS FOR ROAD TRAFFIC ACCIDENTS IN GULU MUNICIPALITY, UGANDA. AB - BACKGROUND: Currently Road Traffic Accidents (RTA) are ranked tenth among the leading causes of death and ninth among all leading causes of disability worldwide. There has been no published study on RTA in Gulu municipality. There is a high frequency of RTA in Gulu municipality with poor road design and inadequate knowledge on road safety precaution among road users. OBJECTIVES: To establish the causes of Road Traffic Accidents (RTA), establish the safety measures in place to protect road users to avoid RTA and establish people mostly involved and the mechanism of RTA. DESIGN: A cross-sectional study. SETTINGS: Four divisions of Gulu Municipality; Layibi, Laroo, Pece and Bardege. SUBJECTS: Two hundred and forty two participants including pedestrians, drivers of different categories of vehicles, motorcyclists and bicyclists locally known as boda-boda and the police were interviewed. RESULTS: Most respondents reported RTA as a problem in Gulu municipality (96%), causing death (48%), financial constraint due to medical treatment (41%) and disability (11%). The following causes of RTA were identified; reckless driving and riding (49%), poor road design (24%), drug abuse (15%) and over loading (12%). According to police records of January to September 2009 RTA involved pedestrians (36.34%), passengers (25.80%), motorcyclists (24.88%), pedal cyclists (11.52%) and drivers (3.68%). CONCLUSION: RTAs is a substantial burden in Gulu municipality in Northern Uganda with reckless driving or riding, poor road design, overloading, double parking, inadequate road safety signs and knowledge, were major risk factors. Efforts to reduce RTA in Gulu municipality should aim at addressing these problems. PMID- 26852446 TI - AETIOLOGY, PATTERN AND MANAGEMENT OF ORAL AND MAXILLOFACIAL INJURIES AT MULAGO NATIONAL REFERRAL HOSPITAL. AB - OBJECTIVE: To establish the aetiology, pattern and methods of management of oral and Maxillofacial injuries (OMFIs) seen at the Oral and Jaw injuries unit of Mulago National Referral Hospital (MNRH) Kampala, Uganda, over a ten year period. DESIGN: A descriptive retrospective study. SETTING: Oral and jaw injury unit of Mulago National Referral Hospital, Kampala, Uganda. RESULTS: One thousand two hundred and three patient records met the inclusion. criteria. The age range was 1-90 years with a male: female ratio of 4.5:1. The age-group most affected was the 21-30-year-olds. Road traffic injuries (RTIs) were responsible for 61% (n = 735 of the injuries, interpersonal violence 27.6% (n = 332), accidental falls 12% (n = 142) and firearm injuries 2.2% (n = 27). Of the maxillofacial fractures (n = 1069) isolated mandibular fractures were 62%, isolated mid-facial fractures 24% whereas Pan-facial fractures accounted for 14%. CONCLUSION: The victims of OMFIs were mostly young men between 21 and 30 years of age. The main aetiological factors were road traffic injuries (RTIs) and interpersonal violence (IPV), while the lower third of the face was most often involved. Consistent with findings in other studies, RTI and IPV remain the two main causes of Maxillofacial injuries and public health measures targeting prevention should focus on these areas. PMID- 26852447 TI - CORRELATION OF CLINICAL AND ECHO-CARDIOGRAPHIC SCORES WITH BLOOD "BRAIN NATRIURETIC PEPTIDE" IN PAEDIATRIC PATIENTS WITH HEART FAILURE. AB - BACKGROUND: Recently brain natriuretic peptide (BNP) level has been introduced as a screening test for congestive heart failure (CHF) in children. The current CHF assessment scores are not satisfactory as they use a large number of variables. OBJECTIVE: To evaluate two CHF scores: a modified clinical score and an echocardiographic score and compare them to BNP in paediatric patients. DESIGN: Prospective, hospital based study. SETTING: Two paediatric cardiac referral centres in Khartoum from April to July 2010. SUBJECTS: All patients one month to 18 years of age with the clinical diagnosis of CHF were included. RESULTS: Sixty seven patients were enrolled, 39 (58%) had congenital heart disease (CHD), 27 (32%) had rheumatic heart disease (RHD), and seven (10%) had dilated cardiomyopathy (DCM).Twenty four younger children (88%) and 29 older children (85%) had a high clinical score (severe CHF). Twenty one out of 23 younger children with high echo score (91%) had a high clinical score as well (p-value 0.001). In patients with RHD (all with a high clinical score), 81% had a high echo score. (p-value 0.001). All younger children with a high clinical score (n = 24) had a high level of BNP (p-value 0.00). In older children with a high clinical score 28 out of 29 (96%) had a high BNP level (p-value 0.00). Of patients with RHD and a high echo score (21), 16 (76.2%) patients had high BNP level and five (23.8%) had low level of BNP. All patients with DCM had high echo score and all of them had high levels of BNP (100%) (p-value.0.00). CONCLUSION: We tested clinical and echo scores and proved their value in assessment of CHF in children. The scores correlated well with BNP level. We recommend the use of these scores as well as BNP level in clinical practice. PMID- 26852448 TI - RAPID SITUATION ASSESSMENTS OF ALCOHOL AND SUBSTANCE USE AMONG COMMERCIAL VEHICLE DRIVERS IN NIGERIA. AB - OBJECTIVES: To describe the current situation with respect to substance use and related harms among commercial vehicle drivers, and to identify a range of interventions that could be feasibly implemented to minimise harms related to substance use. STUDY DESIGN: Observational and group interviews. SETTING: Four different motor parks in Ibadan, Nigeria. SUBJECTS: Data were obtained from a sample of commercial vehicle drivers, community and members of the law enforcement agencies. RESULTS: Widespread use of psychoactive substances was reported. New trend of local alcohol beverage generally called 'sepe' tended to have replaced older ones such as palm wine. All substances of abuse were freely available and openly displayed at motor parks except for cocaine and narcotics. There was poor law provision and enforcement of laws prohibiting sale and use around motor parks or while driving. CONCLUSIONS: This study shows the feasibility and value of conducting rapid assessments among commercial vehicle drivers in Nigeria. One outcome of this study is the development of a guide on rapid assessment of alcohol and other substance use assessment and a measure of brief intervention among them. Presentation of these findings should contribute to increased awareness and improved response from the government. PMID- 26852449 TI - MALE INVOLVEMENT IN MATERNAL HEALTHCARE AS A DETERMINANT OF UTILISATION OF SKILLED BIRTH ATTENDANTS IN KENYA. AB - OBJECTIVE: To determine whether there is a relationship between male involvement in maternal health and utilisation of skilled birth attendants (SBAs) after controlling for socio-demographic and maternal characteristics. DESIGN: Data from the Kenya Demographic and Health Survey (KDHS) conducted in 2008-09 were analysed. SETTING: Nationally representative survey in Kenya. SUBJECTS: The unit of analysis was couples who met the inclusion criteria of being married and having had a child in the three years before the survey. RESULTS: The adjusted odds ratio after controlling for other factors indicates that women whose husbands attended at least one ANC visit were more likely to have skilled birth attendance than those whose husbands did not attend any ANC visits [AOR, 1.9; 95 percent CI, 1.09-3.32]. Maternal characteristics that had a statistically significant association with delivery by an SBA included educational level, employment, number of ANC visits, and parity. The province where the couple resided also was statistically significant. CONCLUSION: In Kenya a male partner's participation, through attending ANC visits, is associated with a woman's use of an SBA during delivery. PMID- 26852450 TI - PSYCHO-SOCIAL CHALLENGES OF PATIENTS FOLLOWING ORBITAL EXENTERATION. AB - OBJECTIVE: Orbital exenteration results in devastating functional, aesthetic and psychological losses. We studied the psycho-social challenges of patients following orbital exenteration. DESIGN: Retrospective descriptive study. SETTING: Korle-Bu Teaching Hospital, eye clinic, Accra. SUBJECTS: Ten surviving patients, at least six months post orbital exenteration. RESULTS: Though all the patients were satisfied with the medical results of the surgery, 50% felt strongly uncomfortable or dissatisfied with the cosmetic effect of the surgery. Sixty percent of the patients suffered unwelcome comments and 50% uncomfortable stare from close friends and relations. Sixty percent were not uncomfortable in the company of friends and close relations. CONCLUSION: Our findings call for a counseling plan for our patients while it is also necessary to find ways of improving their cosmesis. PMID- 26852451 TI - HYGIENE PRACTICES IN URBAN RESTAURANTS AND CHALLENGES TO IMPLEMENTING FOOD SAFETY AND HAZARD ANALYSIS CRITICAL CONTROL POINTS (HACCP) PROGRAMMES IN THIKA TOWN, KENYA. AB - OBJECTIVES: To determine the microbial load in food, examination of safety measures and possibility of implementing an Hazard Analysis Critical Control Points (HACCP) system. DESIGN: The target population for this study consisted of restaurants owners in Thika. Municipality (n = 30). Simple randomsamples of restaurantswere selected on a systematic sampling method of microbial analysis in cooked, non-cooked, raw food and water sanitation in the selected restaurants. SUBJECTS: Two hundred and ninety eight restaurants within Thika Municipality were selected. Of these, 30 were sampled for microbiological testing. RESULTS: From the study, 221 (74%) of the restaurants were ready to eat establishments where food was prepared early enough to hold and only 77(26%) of the total restaurants, customers made an order of food they wanted. 118(63%) of the restaurant operators/staff had knowledge on quality control on food safety measures, 24 (8%) of the restaurants applied these knowledge while 256 (86%) of the restaurants staff showed that food contains ingredients that were hazard if poorly handled. 238 (80%) of the resultants used weighing and sorting of food materials, 45 (15%) used preservation methods and the rest used dry foods as critical control points on food safety measures. CONCLUSIONS: The study showed that there was need for implementation of Hazard Analysis Critical Control Points (HACCP) system to enhance food safety. Knowledge of HACCP was very low with 89 (30%) of the restaurants applying some of quality measures to the food production process systems. There was contamination with Coliforms, Escherichia coli and Staphylococcus aureus microbial though at very low level. The means of Coliforms, Escherichia coli and Staphylococcus aureas microbial in sampled food were 9.7 x 103CFU/gm, 8.2 x 103 CFU/gm and 5.4 x 103 CFU/gm respectively with Coliforms taking the highest mean. PMID- 26852452 TI - FACTORS INFLUENCING CONDOM USE AMONG NIGERIAN UNDERGRADUATES: A MIXED METHOD STUDY. AB - OBJECTIVE: This study's objective was to explore and assess the factors influencing condom use among Nigerian undergraduates within the age group 16-34 years. SETTING: The University of Lagos, a federal University in the commercial capital of Nigeria. STUDY DESIGN: Both qualitative (focus group discussions) and quantitative (cross-sectional survey) methods were utilised for this study. SUBJECTS: A total of 101 subjects were recruited with age range 18 to 34 years as against 100 years, with a mean age of 21 years. Data collection was conducted in July and August 2011 at the University of Lagos. SUBJECTS: A total of 820 students from University of Lagos in four faculties participated in the cross sectional survey, and we organised four focus group discussions with six students each. RESULTS: Students were of the perception that various socio-economic and environmental factors influenced condom use during sexual intercourse. Factors identified as having great influence on condom use include: "adequate sex education" and "unplanned/ unanticipated sexual intercourse". Conversely, the influence of alcohol/social drugs on condom use was ranked low. CONCLUSION: The study showed that students had the perception that various factors influenced condom use but these perceptions varied between young men and women. It may therefore be rewarding to have customised messages based on specific needs when reaching out to different groups stratified based on gender. PMID- 26852453 TI - HISTOPATHOLOGICAL EVALUATION OF H. PYLORI ASSOCIATED GASTRIC LESIONS IN BENIN CITY, NIGERIA. AB - BACKGROUND: Endoscopic biopsy of the gastric mucosa allows early diagnosis, grading, staging and classification of gastric diseases. Helicobacter pylori, has been recognized as a major aetiologic factor for chronic gastritis, benign gastric ulcers and gastric adenocarcinoma and lymphoma. The loco-regional variability in the prevalence of Helicobacter pylori and associated diseases in Nigeria, emphasise the need for evaluation of subsets of a heterogeneous population like ours. OBJECTIVE: To determine the frequency of helicobacter pylori in gastric endoscopic biopsies and document the pathology of gastric lesions commonly associated with Helicobacter pylori infection. DESIGN: Retrospective descriptive study. SETTINGS: University of Benin Teaching Hospital (UBTH), and Biogenics Histopathology Laboratory (a private Histopathology Laboratory), both based in Benin City, Niger Delta region of Nigeria. SUBJECTS: Endoscopic gastric biopsies recorded in the surgical pathology register of the department from 2005-2009 were studied and relevant demographic and clinical information extracted from the registers, original request cards and patient case files. The clinical data and slides processed from paraffin embedded tissue blocks of endoscopic biopsies of gastric lesions seen from year 2005 to 2009 were studied, analyzed and statistically presented. RESULTS: Total number of specimens studied was 142. Chronic gastritis was present in 117(82.39%) specimens; 9(6.34%) were benign gastric ulcers; 3(2.11%) were gastric polyps; and 11(7.75%) were gastric malignancies. Helicobacter pylori, was demonstrated in 55.6% of all specimens. The peak age for Chronic Gastritis and Gastric Cancer is the 6th decade. Amongst patients with chronic gastritis, inflammatory activity was present in 65%; atrophy in 53%; and intestinal metaplasia in 16.6%. All gastric malignancies seen were intestinal type adenocarcinomas. CONCLUSION: The spectrum of lesions diagnosed in gastric endoscopic biopsy specimens in Benin, their frequency and associations are largely comparable to what has been described elsewhere in Nigeria and Africa. PMID- 26852454 TI - ATTITUDE OF CLEFT CARE SPECIALISTS IN AFRICA TOWARDS PRESURGICAL ORTHOPAEDICS. AB - OBJECTIVE: To determine the attitude of cleft care specialists working in Africa towards pre-surgical orthopaedics. DESIGN: A cross sectional study. SETTING: Pan African conference on cleft lip and palate in Nigeria. SUBJECTS: Sixty cleft care specialists working in Africa. RESULTS: The general attitude towards pre surgicalorthopaedics was positive. Majority of the specialists employ pre surgical orthopaedics before surgical repair. Fifty four (91%) of the specialists use plaster strapping for cases of bilateral cleft, five (8.3%) use nasoalveolar molding and one (2%) use feeding plate. Half of the specialists (50%) felt that pre-surgical orthopaedics is to be managed by orthodontists alone. There were significant difference in attitude towards pre-surgical orthopaedics between providers (p < 0.05). Orthodontists had a strong positive attitude towards pre surgical orthopaedics than other specialists. Younger specialists had a more positive attitude towards pre-surgical orthopaedics than older specialists. CONCLUSION: Cleft care specialists in Africa have a positive attitude towards pre surgical orthopaedics. Majority of them use plaster strapping technique. Younger specialists have a more favorable attitude towards pre-surgical orthopaedics than older specialists. PMID- 26852455 TI - ROLE OF ABDOMINAL ULTRASOUND IN EVALUATION OF CHILDREN WITH SUSPECTED UPPER GASTROINTESTINAL DISEASE. AB - OBJECTIVES: To evaluate the sonographic abdominal findings in children with suspected upper gastrointestinal disease, establish indications for sonography and describe the gastrointestinal disease patterns that can be evaluated by ultrasound. DESIGN: Descriptive prospective study. SETTING: Kenyatta National Hospital and Department of Diagnostic Imaging and Radiation Medicine, University of Nairobi. SUBJECTS: Fifty-six children who presented with vomiting and suspected upper gastrointestinal disease. Age range was from six days to 12 years with mean age of one year five months. Seventy seven percent were two years and below. RESULTS: Of the 56. children, six were normal on sonography; 18 (32.1%) had intussusception, 16 (28.6%) gastroesophageal reflux, seven (12.5%) pyloric stenosis, four appendicitis, three jejunal/ileal atresia and two enteric duplication cysts. All the children with pyloric stenosis were male. The male: female ratio for intussusception and GER was 1.5:1 and 1.6:1 respectively. The most common clinical presentation in children found to have intussusception was palpable abdominal mass, and few of them presented with bloodstained stool. More than two thirds of the children with gastro-oesophageal reflux presented with complications of recurrent pneumonia and failure to thrive. The sonographic findings correlated with fluoroscopy for GER except in two children where sonography was found to be more sensitive. The sonographic findings correlated with surgical outcome for pyloric stenosis, intussusception,jejunal/ ileal atresia and enteric duplication cysts. CONCLUSION: Trans-abdominal sonography has a definite role in investigating the child suspected to have upper gastrointestinal disease and should be considered as the initial imaging modality, instead of fluoroscopy, thereby avoiding or limiting the use of ionising radiation. Findings in this study confirm that ultrasound is an accurate, reliable and rapid screening method to evaluate the causes of upper gastrointestinal disease in children. PMID- 26852456 TI - ROUTINE RADIOGRAPHIC FINDINGS IN CLINICALLY HEALTHY EDENTULOUS JAW BONES OF PATIENTS SEEKING THEIR FIRST SET OF COMPLETE DENTURE PROSTHESES. AB - OBJECTIVE: To describe the role of routine radiographic examination of clinically healthy completely edentulous jaws prior to fabrication of the first set of complete dentures. DESIGN: Cross-sectional retrospective descriptive study. SETTINGS: The departments of Conservative and Prosthetic Dentistry, and Oral and Maxillofacial Surgery, Oral Medicine/Oral Pathology, Dental Maxillofacial Radiology of the School of Dental Sciences, University of Nairobi. RESULTS: One hundred and eighty eight records were examined of which only 47(25%) had radiographic records. One hundred and fifty two significant radiographic findings and indices were recorded, which included retained roots, impacted teeth, significant radioluscencies and radiopacities, calcified stylohyoid ligament, extensive alveolar bone resorption, condylar changes and mandibular cortical index. CONCLUSION: This study confirms the high diagnostic yield of routine preprosthetic treatment radiographic examination. It also puts into perspective various anatomical indices in the jaw which, with proper interpretation, may determine or influence management decisions and prognosis in individual patients. PMID- 26852457 TI - ZIEHL-NEELSEN MICROSCOPY IN THE DIAGNOSIS OF TUBERCULOSIS IN SETTINGS OF HIGH HUMAN IMMUNODEFICIENCY VIRUS PREVALENCE. AB - OBJECTIVE: To determine the accuracy of Ziehl-Neelsen microscopy in the diagnosis of TB in setings of high HIV prevalence. DESIGN: Cross-sectional descriptive study. SETTING: Hospitals serving areas of high human immunodeficiency virus prevalence in western Kenya. The study was conducted between September 2007 and September 2009. RESULTS: In total, 341/872(39.1%) of the TB suspects were positive in ZN, 53.1% (181/341) of them culture positive. Only 3.8% (20/531) of the ZN smear negatives were culture positive. Of the 695 suspects evaluated for both Mycobacterium and HIV infection, 255 (36.7%) were ZN smear positive, 42.7% of them HIV positive. Out of the 440 ZN smear negatives, 37% were HIV positive. Similarly, 168 suspects were culture positive, 46.4% of them HIV positive. The HIV infection did not significantly reduce ZN smear positivity rate (P = 0.42) and culture sensitivity (P = 0.09). The ZN sensitivity and specificity were 88.1% and 79.7%, respectively. The predictive values were 58.0 (PPV), and 95.5% (NPV), respectively. However, the area under the ROC curve was 0.84, with 95% CI between 0.80-0.87 and P < 0.001). The ZN smear microscopy had a lesser ability to distinguish between TB and non-TB cases compared to culture. CONCLUSION: ZN microscopy causes a significant over-diagnosis of TB in settings of high HIV/AIDS prevalence. There is need for further studies on this subject taking into consideration the various confounding factors. PMID- 26852458 TI - EVALUATING CHAMBERLAIN'S, McGREGOR'S, AND McRAE'S SKULL-BASE LINES USING MULTI DETECTOR COMPUTERISED TOMOGRAPHY. AB - BACKGROUND: Traditionally the cranio-cervical junction is assessed by lateral cervical spine and base of skull radiographs which however have diagnostic challenges due to the complexity of the anatomy. Modern day Computed Tomography (CT) offers excellent bony detail and its ability to reconstruct the acquired CT data into various imaging planes makes the assessment of the cranio-cervical junction easy and more accurate. OBJECTIVE: To evaluate the relationship of the odontoid peg of C2 to the standard skull base lines of Chamberlain's, McGregor's and McRae's on computed tomography. DESIGN: Descriptive cross-sectional study. SETTING: Kenyatta National Hospital, Nairobi, between April and September 2010. RESULTS: The mean position of the odontoid process was 2.6 mm below Chamberlain's line (median 2.7 mm, SD 2.2 mm), 1.0mm (median 0.9 mm, SD 2.1 mm) below McGregor's line and 4.7 mm (median 4.6 mm, SD 1.3 mm) below McRae's line. There was no statistically significant difference in measurements between male and female patients, the different age groups and between CT and standard plain radiograph measurements (p > 0.05). CONCLUSION: Anthropometric measurements obtained using CT were lower than those from plain radiographs. There was howeverno statistical significant difference between the two imaging modalities. CT demonstrated far much superior anatomical detail compared to plain radiographs. PMID- 26852459 TI - CLINICAL EPIDEMIOLOGICAL PROFILE OF VITILIGO. AB - BACKGROUND: Vitiligo is an acquired de-pigmenting disorder of unknown aetiology affecting 1-2% of the world's population. It is a chronic skin disease, characterised by the appearance of white depigmented macules and patches due to loss of melanocytes. This disorder is common in all races, regardless of age and sex. The onset of the disease may vary from early infancy to old age. OBJECTIVE: To determine the clinical and epidemiological characteristics of patients with vitiligo. DESIGN: This was a cross sectional descriptive study. SETTING: Regional Dermatology Training Centre in Moshi, Tanzania. SUBJECTS: One hundred and twenty two patients. RESULTS: The male to female ratio was 1:1.8 and a median age of 24 years (range 3 to 87). The mean age at disease onset was 26.2 years (SD 19.5). The types of vitiligo observed were as follows: vitiligo vulgaris (50.8%) focal non segmental (23%) and Acrofacial (12.3%). Positive family history was noted in about 10% of the population studied. The commonest sites of initial onset were head and neck (41.8) and lower limbs (18.0%). The median body surface area affected was 6% (range 1 to 90%). Autoimmune diseases were noted in 17.2% of the patients. Atopic dermatitis (9.8%) was the most common associated disease. CONCLUSION: Vitiligo affects all ages with more females affected. Vitiligo vulgaris is the commonest type and few patients have first degree relatives with vitiligo. PMID- 26852460 TI - SURGICAL MANAGEMENT OF AGGRESSIVE SYNCHRONOUS JAW CENTRAL GIANT CELL GRANULOMA: CASE REPORT. AB - Central giant cell granuloma (CGCG) appears to be a lesion that is unique to the jaws. It is difficult to predict its aggressiveness. A rare case of synchronous CGCG of the mandible and maxillar in a 14-year old boy is presented. PMID- 26852462 TI - APPROVED: New Requirements for Residential and Outpatient Eating Disorders Programs. Effective July 1, 2016, for Behavioral Health Care Accreditation Program. PMID- 26852461 TI - APPROVED: New Advanced Certification for Total Hip and Total Knee Replacement Program. PMID- 26852463 TI - APPROVED: Permanent Housing Support Services Standards. PMID- 26852464 TI - More on Managing Hazardous Materials and Waste. A Further Examination into EC.02.02.01. PMID- 26852465 TI - Consistent Interpretation. Joint Commission Surveyors' Observations on Requirements. PMID- 26852466 TI - Why Research Matters. PMID- 26852467 TI - 3 Engagement Trends in Health Care Content. PMID- 26852468 TI - Is Convenience Ruining Your Brand? PMID- 26852470 TI - 7 Secrets of Engaging Online Video Scripts. PMID- 26852469 TI - 5 Ways to Improve Your Online Reputation. PMID- 26852471 TI - THE ELEPHANT IN THE ROOM. PMID- 26852473 TI - 10 Minutes With DANIELA CAMPARI. PMID- 26852472 TI - IT'S PERSONAL. PMID- 26852474 TI - WHAT THE DOCTOR ORDERED. PMID- 26852475 TI - [Effect of Ultrasmall Gold Nanoparticles on the Murine Native Sperm Chromatin]. AB - The effects of ultrasmall (2-3 nm) gold nanoparticles on native epididymal sperm chromatin of CBAxC57BL/6 hybrid mice and 129/IMG mice with a mutation in the DNA polymerase iota gene were studied. It is shown that for both mouse strains after sperm incubation in a solution containing Au nanoparticles, at 23, 37 and 60 degrees C for 30 min followed by 1 hour treatment in dithiothreitol solution, a decrease in the number of nuclei with fully decondensed chromatin was observed compared with the control. Though, the manifestation of this effect in the population of 129/IMG mice mature sperm, was weaker. Also we have demonstrated that sperm of both strains that were incubated in a sol of Au nanoparticles at 60 degrees C behave differently under the action of dithiothreitol. A considerable part (-80%) of sperm of CBAxC57BL/6 hybrid mice treated with Au nanoparticles showed high resistance to the action of dithiothreitol, whereas in the case of 129/IMG mice only -30% did, and a partial or complete chromatin decondensation takes place in the remaining sperm. In general, using the method of nuclear chromatin decondensation in vitro for the native sperm, the patterns that we have identified in earlier studies on previously demembranized sperm are confirmed. PMID- 26852476 TI - [Metabolites of Toxigenic Fungi in Lichens of the Genera Nephroma, Peltigera, Umbilicaria, and Xanthoria]. AB - The component composition of mycotoxin complexes is characterized in foliose lichens of the genera Nephroma, Peltigera, Umbilicaria, and Xanthoria. The interspecies differences in the genus Peltigera are expressed by the number of metabolites detected, from seven in P. aphthosa to three in P. canina, P. didactyla, P. praetextata, and P. rufescens. In Nephroma arcticum eight mycotoxins occurred regularly, with mycophenolic acid in especially high quantities in comparison with other lichens. In Umbilicaria, of six permanent components the content of alternariole is the highest, and in Xanthoria the content of emodine is the highest. Variation of the quantitative content of mycotoxins in general and of species of lichens is discussed, as is expansion of the background spectrum of these metabolites in collections from different territories. PMID- 26852478 TI - [The Position of "Lower Plants" on the Tree of Life]. AB - It was shown that, in contrast to higher plants, lower plants are a group of organisms that are very different in origin and kinship. PMID- 26852477 TI - [Comparative Characteristics of the Lipid and Fatty Acid Status of Eyed-Stage Atlantic Salmon Embryos Reared in Natural and Artificial Environments]. AB - The lipid status of Atlantic salmon (Salmo salar L.) embryos has been compared between embryos developing in incubator nests installed in the natural environment (UmbaRiver, Kola Peninsula) and those developing in a laboratory (in aquaria). The developmental stage of eye pigmentation selected for comparison is characterized by the highest sensitivity of the embryos to environmental factors. The content of certain classes of total lipids and fatty acids was different between the two groups of embryos, and the ratios between the relative content values for some of the compounds were different as well. The difference may be due to environmental factors (temperature, oxygen levels, running water in the nests, etc.) affecting the developing embryos, and they may determine the subsequent embryonic and postembryonic development of the fish. PMID- 26852479 TI - [Similarities and Differences in Wheat Plant Responses to Low Temperature and Cadmium]. AB - A comparative study was performed on the accumulation of biomass, dynamics of indicators of the activity of photosynthetic apparatus, and cold tolerance in the seedlings of frost-tolerance wheat varieties under the effect of a low hardening temperature and cadmium. It was found that the plant responses to the effects of the stressors studied are similar: an increase in cold tolerance of leaves, slowing rates of plant growth and photosynthesis, and increased non-photochemical fluorescence quenching were observed in both cases. At the same time, it was noted that the plant responses to the actions of low temperature and Cd have certain differences associated with the negative effect of Cd on growth and photosynthetic activity. PMID- 26852480 TI - [Shell Variability of the Terrestrial Mollusk Chondrula tridens (Pulmonata, Enidae) in the Forest-Steppe Zone of the Volga Upland]. AB - Shell variability of the steppe mollusk Chondrula tridens from 18 micropopulations in the forest-steppe zone of the Volga Upland was studied. It was found that larger specimens of Ch. tridens with well-developed teeth inhabit the central and eastern parts of the territory. Specimens in the northwestern part of the upland are characterized by small shells, the highest degree of roundness, and mostly reduced teeth in the mouth. The main factors that determine variability in the size and proportions of shells are the average daily temperatures increasing from the northwest to the south, the reduction in the total precipitation, the decrease in the soil moisture content, and, possibly, the increased content of carbonates in the soil. PMID- 26852481 TI - [Influence of the Mother on the Behavior of Young Rabbits during the Prepubertal Period]. AB - In this study, we investigate the influence of a mother on the behavior of young rabbits during the prepubertal period. It is shown that the presence ofthe mother affects the ratio of types of activity in offspring and the mother can demonstrate behavioral patterns to suppress aggressive behavior in offspring. It was found that rabbits in the prepubertal period continue to have active contact with their mother and make successful attempts at sucking. It was noted that, in terms of percentage, both in the frequency and duration of different forms of activity among rabbits from one to three months of age, a neutral socially oriented and feeding behavior appear to be predominant. There were significant differences in the frequency of the socially oriented behavior and the duration of feeding behavior in young rabbits, who grew up with their mother and without her. PMID- 26852482 TI - [World Collections of Parasitic Worms]. AB - This article provides information about the depositories of parasitic worms in the scientific institutes and museums in the United States, Japan, and Europe (the total number of samples and the availability of types of helminths from various classes), as well as information on the availability of electronic catalogues of the collections in the continental, national, and regional centers for collective use. The extent of this material has determined the necessity of creating digital collections and libraries that would represent a new form of storing, displaying, and exchanging information for scientific research. An analysis was performed of the current state of approaches and methods of development of the specialized information retrieval system (IRS) and databases (DBs) on the parasitic worms in Russia on the basis of a common conceptual data model, taking into account their local use (as desktop systems of database management) and access by scientists worldwide via the Internet. PMID- 26852483 TI - [Peptide Regulation of Metabolic Processes under Hypercholesterinemia Conditions of an Organism]. AB - The participation of short glyproline peptides in regulating the metabolic processes of the body has been established. Experimental hypercholesterolemia and the development of metabolic syndrome in rats was caused by including foods with excess animal fat and carbohydrates in the diet, which eventually led to increased levels of cholesterol, triglycerides, and the atherogenic lipoproteins; hypercoagulation; and increased blood sugar. It was noted that glyprolines with different structures possess a unique combined effect on fat and carbohydrate metabolism, normalizing the characteristics of the lipid profile and blood sugar and protecting the organisms of animals from increased blood clotting. The idea of peptide regulation of the hemostatic system and metabolism of fats and carbohydrates in the development of metabolic syndrome was formulated. PMID- 26852484 TI - [Peculiarities of Phenology of the Primary Production Process in the Pelagic Zone of Lake Onega]. AB - The peculiarities of the phenology of the primary production process of phytoplankton have been studied for a large northern lake. The major seasonal events ofthe primary production process and the seasonal dynamics of the abiotic and biotic environmental factors have been-described using the average multiyear curves of the studied parameters in the pelagic zone of Lake Onega. The primary production seasonal cycle is synchronized to the water temperature dynamics, Chlorophyll a concentration (phytoplankton), and the density of "nondiatom" phytoplankton. The seasonal dynamics of the diatoms exhibits the opposite pattern. The temperature coefficient of photosynthesis (Q10) has been calculated for the natural phytoplankton community for the different seasons of vegetation period. The phenological phases of the primary production have been defined. PMID- 26852485 TI - [Effects of the Vital Activity of Soil Insect Larvae on Microbial Processes in the Soil]. AB - The effects of Elateridae larvae (wireworms) on the structure, functional diversity, and tolerance of the soil microbial population in steppe ecosystems have been investigated. The trophic and locomotor activity of wireworms leads to an appreciable increase in bacterial abundance and suppression of fungal activity. The fungal hyphae in the presence of wireworms are significantly damaged, which can be related to the feeding activity of Elateridae. The increase of bacterial abundance on the background of exclusion of the fungal component shifts the microbial succession to the acceleration of organic matter mineralization. The microbial consumption of mono- and oligosaccharides, alcohols, and water-soluble compounds increases in the presence of wireworms (multisubstrate test). The effect of Elateridae larvae on the microorganisms transforming nitrogen compounds is species-specific. Agriotes obscurus activity decreases their consumption of urea and creatinine by 2.1-2.5 times, and Selatosomus aeneus increases it by 1.3 and 2.5 times, respectively. The intensity of actual nitrogen fixation in the soil increases in the presence of wireworms by almost 4 times, but the losses of gaseous nitrogen do not increase because of the decrease in both the denitrification and methanogenesis rates PMID- 26852486 TI - [Factors Affecting the Dynamics of Circadian Activity of Frit Flies Meromyza saltatrix (L) (Diptera: Chloropidae)]. AB - The dynamics of circadian activity in adult frit flies of the Holarctic species Meromyza saltatrix (L) from Mongolian, Moscow, and Polish populations was studied. Synchronous peaks of activity were revealed with the periodicity multiple of three-four hours, which may depend on the level of light. The direct effect of temperature and humidity on the activity of flies outside the optimal values of these factors was found. It was detected that the peak of adult emergence falls on the beginning of a general increase in the abundance of flies, which indicates constant rejuvenation of the population. The sex ratio is close to 1, but the emergence of males and females is in antiphase. The synchronization of peaks of circadian activity in the populations from different regions confirms the presence of a circadian rhythm of activity. The rhythm synchronizing the reproductive activity of adults was found to be modified by the photoperiod under the optimum conditions of temperature and humidity. PMID- 26852487 TI - [Certain Blood Values of the Siberian Roach Rutilus rutilus in Affected Area of Warm Water from Gusinoozerskaya State District Power Plant (Eastern Siberia)]. AB - The erythron parameters of Siberian roach inhabiting Gusinoe Lake were determined for the first time in an area of warm water discharged from the Gusinoozerskaya State District Power Plant (SDPP) (Eastern Siberia). It was noted that the defects of erythropoiesis identified (degenerative changes in the cytoskeleton, cytoplasm structure, and erythrocytes nuclei and a tendency to the development of hypochromic anemia) were obviously due to the combined impact of chemical and heat pollution of the water area of Gusinoe Lake by water discharged from the SDPP. PMID- 26852488 TI - [Modification of Levels of Adhesion Molecule Expression of Human Innate Immune Cells by Glycopolymers of Marine Bacteria]. AB - By flow cytometry it was demonstrated that lipopolysaccharide and exopolysaccharide of marine proteobacteria Pseudoalteromonas nigrifaciens alter the expression of adhesion molecules on human neutrophils and monocytes, reducing the expression level of molecules CD62L and increasing the expression of CD11b, CD11c and CD54. PMID- 26852489 TI - [Investigation of Prophylactic Efficacy of Triazavirin Against Experimental Forest- Spring Encephalitis on Albino Mice]. AB - Prophylactic efficacy of Triazavirin against experimental Forest-Spring encephalitis was studied on albino mice. vs. the active drug Ribavirin. A significant increase of the animal lifespan in the test groups (from 4 to 5 days) and a statistically (p < or = 0.05) valid decrease of the virus accumulation level in the target organ (the brain) were observed. PMID- 26852490 TI - [Remaxol in Correction of Functional Hepatic Failure in Patients with Acute Biliary Pancreatitis]. AB - The effcacy of Remaxol was studied in the treatment of patients with acute biliary pancreatitis under clinical and laboratory con- ditions by the recommended indices, as well as by the markers of endogenous intoxication, the intensity of lipid peroxidation, activity of some enzymes and indicators of hypoxia. The use of Remaxol in the treatment of acute biliary pancreatitis was highly resultant in correction (prevention of progression) of the functional hepatic failure and homeostatic disorders as a whole. It was demonstrated that the hepatoprotective effect of the drug was based on its ability to reduce oxidative stress, to inhibit excessive phospholipase activity and to alleviate the signs of general hypoxia. PMID- 26852491 TI - [Toxoplasmosis: Epidemiology, Diagnosis, Treatment]. AB - The up-to-date literature and original data on the epidemiology, diagnosis and treatment of toxoplasmosis are presented. Particular attention is paid to the parasite infection during pregnancy. Spiramycin is the drug of choice for acute toxoplasmosis in pregnant women. PMID- 26852492 TI - [A clinical Case-of Icenko-Cushing Syndrome in a Female Patient with Morbit Obesity after Bariatric Surgery]. AB - The efficacy of morbid obesity therapy at present remains rather low. Bariatric surgery is one of the most efficient methods for the treatment. Safety, efficacy and favourable results of the surgery are provided only after thorough examination of the patients. PMID- 26852493 TI - [On Biofilms of Streptomycetes. II. Use in Biotechnology]. AB - Streptomycetes or mycelial microorganisms are able to form biofilms under the natural, industrial and clinical conditions. The controlled use of biofilms in various industrial processes is much more efficient vs. the cultivation of plankton suspended cells. Optimization of biotechnological processes with the use of streptomycete biofilms is advisable in production of lactic acid and detoxication of the liquor in pyrolysis of plant biomass. Streptomycete biofilms are used in water purification systems. It is recommended to use biofilms for detoxication of wastes and bioremediation of soils contaminated with hard metals. The use of biofilms of streptomycetes producing biologically active substances is of special interest. High yields of.antibiotics and actinomycin D in particular was observed with. cultivation of antibioc-producing streptomycetes as biofilms in bioreactors of unique design. PMID- 26852494 TI - [Up-to-Date Aspects of Antihypertensive Therapy from the Viewpoint of Cardio- and Nephroprotective Action: Olmesartan]. AB - The literature data on possible optimization of the arterial hypertension management with organoprotective antihypertensive agents are reviewed. Omesartan is one of the most thoroughly investigated agents blocking the receptors to angiotensin-II that shows antihypertensive effect and has cardiovaso- and nephroprotective as well as pleotropic properties. The use of Olmesartan is based on the principles of proof medicine. PMID- 26852495 TI - [The factors influencing the recovery of the patients suffering from stroke during the rehabilitation period]. AB - In this article, the results of the authors' research, including analysis of the clinical and instrumental data concerning 203 patients with stroke, are presented. The factors significantly affecting the recovery of patients in the rehabilitation are determine, viz. the age, the presence of the chronic pain, the level of education, the nature of the pathological process in the brain (the stroke type), the localization of the lesion (hemispheric, stem), right/left sided localization of the lesion, the width of the lesion, the volume of the lesion (the atrophic post-ischemic changes, the volume of hematoma), the presence of cerebral atrophy (the width of the third ventricle), the presence of leukoareosis, the presence and the severity of stenosis in the internal carotid artery, the operations on the main arteries in the medical history, the presence of focal lesions on the electroencephalogram, the presence of the perifocal brain edema, accompanied by a shift of midline structures in the acute phase of stroke, the incidence of the stroke. We distinguished the "rehabilitation subgroups" according to the representation of the basic and additional risk factors. The influence of leukoareosis on the recovery of patients after hemorrhagic stroke in shown for the first time. The values of each risk factor for the patients presenting with ischemic stroke of hemisphere and stem localization, as well as for the patients with intracerebral hematomas were calculated. The prognostically significant percentage of the clinical improvement of the patients' conditions in the course of rehabilitation for each of the subgroups is estimated. PMID- 26852496 TI - [The peculiarities of the application of transcranial magnetic therapy and electrical stimulation for the treatment of the patients presenting with various types of stroke]. AB - In this article, the results of the authors' research, including analysis of the clinical and instrumental data concerning 203 patients with, stroke are presented. It is shown that the clinical effectiveness of the transcranial methods incorporated in the combined rehabilitation programs depends on the type of stroke and localization of the lesions. Specifically, the patients presenting with ischemic stroke of hemispheric localization experienced a neurophysiologically confirmed significant clinical improvement that became apparent after the consistent application of transcranial magnetic therapy and micropolarization. In the patients with ischemic stroke of stem localization, the positive influence on psychomotor recovery was achieved with the application of transcranial magnetic therapy, but transcranial micropolarization did not have an appreciable effect on the recovery of such patients. The patients presenting with hemorrhagic stroke did not experience any significant improvement of psychomotor parameters from transcranial magnetic therapy and transcranial micropolarization. The likely mechanism underlying the recovery of psychomotor processes under effect of transcranial magnetic therapy in the patients with ischemic stroke is the normalization of the frequency of interaction between brain structures. In addition, in the patients with ischemic stroke of hemispheric localization and in the patients with hemorrhagic stroke electrical myostimulation has a marked impact on the psychomotor recovery only in case of functional treatment. In the patients suffering from ischemic stroke of stem localization non-functional electromyostimulation significantly improves motor functions and cognitive motor control. PMID- 26852497 TI - [Early diagnostics, prophylaxis, and non-pharmacological treatment of the preclinical stages of atherosclerosis and arterial hypertension]. AB - Cardiovascular diseases remain the leading cause of death in most countries, including Russia. Non-pharmacological-modalities intended for the primary prevention of cardiovascular disease including hypertension and atherosclerosis currently acquire special significance. The objective of the present*study was to develop a system of methods for early diagnostics, prevention and treatment of the preclinical stages of atherosclerosis and hypertension Another objective was to estimate the effectiveness of these methods. A total of 310 patients at risk of arterial hypertension and atherosclerosis or with pre-clinical stages of these conditions were examined during a two year observation period. The system of early diagnosis and non-pharmacological primary prevention of cardiovascular disease was developed and evaluated using climatotherapeutic and physiotherapeutic methods in combination with and personalized dietary therapy, hypoxic-hypercapnic factors and educational programs. The study has demonstrated that the proposed system allowed to significantly (p < 0.05) reduce cardiovascular morbidity. The patients of the main group experienced the reduction of abdominal obesity and blood pressure along with the improvement of the blood lipid profile and other indicators. These parameters remained unaltered in the patients comprising the control group. In the main group, the incidence of coronary heart disease and hypertension was 62.5% and 81.25% lower respectively than in the control group. PMID- 26852498 TI - [The application of the method of kinesio-taping technique for the combined non pharmacological rehabilitation of the patients presenting with lymphedema of the lower extremities]. AB - Based on the innovative "kinesio-taping" technique proposed by the Japanese researcher Kenzo Kace, we have designed a new physiotherapeutic complex including the well-known physiotherapeutic methods of lymphatic drainage with intermittent pneumatic compression and underwater massage shower. The objective of our study was to evaluate the efficiency of the application of the "kinesio-taping" technique for the non-pharmacological rehabilitative treatment of the patients presenting with stage I-III lymphedema of the lower sextremities. The secondary objective was to evaluate the possibility of correction of endothelial dysfunction in the patients with lymphedema after the application of the "kinesio taping" technique. The study included 30 patients with stage I-III lymphedema of the lower extremities randomized into two groups. Group 1 was comprised of 15 patients who were consistently treated by a combination of intermittent pneumatic compression, "akinesio-taping", and underwater massage shower. Group 2 contained 15 patients treated with the use of intermittent pneumatic compression and underwater massage shower. The results of study give evidence of positive changes in microcirculation of the patients comprising group 1 that suggest the improvement of endothelial function, vasodilation of precapillaries, enhancement of the blood flow in the microcirculatory system, and reduction of the influence of the ineffective shunting blood flow. The data obtained confirm the effectiveness of the new non-pharmacological rehabilitation complex that includes the innovative lymph-draining method of kinesio-taping, intermittent pneumatic compression and underwater massage shower for the treatment of patients with lymphedema of the lower extremities. The effectiveness of this complex is due to combined stimulation of the lymphatic and venous drainage systems and coupled to the stimulation of blood flow in the microcirculatory bed and the formation of a positive endothelial response. PMID- 26852499 TI - [Rehabilitation of the patients with osteoarthritis]. AB - Under the term "osteoarthritis" (OA) is currently meant a clinical syndrome resulting from the combined effect of articular pain and disordered functional activity leading to the deterioration of the quality of life of the patients. The principal objective of rehabilitation of the patients presenting with GA in which all patients with this condition are in need practically after each next aggravation of the pathological process is to relive pain syndrome and restore the functional ability of the joints lost or deteriorated after each exacerbation in order to eventually improve the quality of life of the patients experiencing the constantly progressing degenerative process in the musculoskeletal system. The effectiveness of pain alleviation, the degree of improvement'of the joint functional activity and the general condition of the patient are considered as the criteria for the assessment of the effectiveness of the rehabilitative treatment. These criteria have been chosen in accordance with the recommendations of the OMERACT international working group (outcome measures in rheumatology). In addition, the quality of life associated with the health status and the adverse effects of the rehabilitative measures were estimated. Bearing in mind comorbidity in the patients presenting with OA, one of the main challenges is the development of the scientifically sound rationale for the application of non pharmacological technologies of physical therapy, remedial gymnastics and massage for the prevention and elimination of an aggravation of the secondary aseptic inflammatory process associated with OA and the subsequent rehabilitative treatment for the restoration of the lost locomotory stereotype and the quality of life of the patients. One of the effective methods of physical therapy used for the treatment and rehabilitation of the patients presenting with GA is hyperbaric gaseous cryotherapy. This method makes use of the heat rejection phenomenon to which the organism responds, either in the compensatory or/and reflectory mode, by the activation of the heat production processes in the tissues due to the stimulation of the metabolic processes as well as the vascular, neuroendocrine, and immune systems involved in the regulation of homeostasis which produces the desired therapeutic effect apparent as the cessation of secondary aseptic inflammation and progressive degeneration process associated with OA. Taking into consideration the aforesaid, the objective of the present study was the scientifically sound substantiation of the application of hyperbaric gaseous cryotherapy as a constituent of the combined rehabilitative treatment of the patients presenting with gonarthritis and a coxarthrosis. This article was designed to report the results of such combined treatment obtained in 110 patients (22 men and 88 women) with gonarthritis and a coxarthrosis of the II III stages (based on the classification of Kellgren). The patients aged from 40 to 75 years which were randomly divided into two groups (the main and the control (comparison) groups) comprising 55 patients each. The patients of the main group, unlike those in the control one, were treated with the use of hyperbaric gaseous cryotherapy in addition to traditional physical therapy and balneotherapy, therapeutic physical exercises, and massage. The results of the treatment were evaluated making use of the Lequesne, WOMAC, Likert international indices. It allowed to identify the predictors for the use of hyperbaric gaseous cryotherapy and to increase the effectiveness of the rehabilitative treatment of the patients suffering from OA of the large joints by 33% in comparison with the control group. The highest clinical effectiveness of 90% was achieved in the cases of at a.gonarthritis; it was somewhat lower (64%) in the cases of coxarthritis. PMID- 26852500 TI - [The results of the combined application of extracorporeal shock-wave therapy and radon baths during the rehabilitative treatment of the patients presenting with gonarthrosis]. AB - Osteoarthritis (OA) is one of the leading diseases of the musculoskeletal system and the main cause of arthritic joint damage. AIM: The objective of the present study was to evaluate the effectiveness of the combined application of radon baths and shock-wave therapy in the patients suffering from knee OA. PATIENTS AND METHODS: The study involved 75 patients at the age of 35 to 62 years with the confirmed diagnosis of stage II and III gonarthrosis; they were divided into 3 groups. The patients of the main group received the combined treatment including extracorporeal shock-wave therapy and radon baths The patients comprising the group of comparison were given the course of radon therapy alone while those in the control group were offered the standard treatment including physiotherapy, magnetic therapy, and NSAIDs. RESULTS: The study has demonstrated the high effectiveness of the combined application of the radon baths and extracorporeal shock-wave therapy for the rehabilitation of the patients with deforming arthrosis of the knee that was apparent from the substantial decrease of pain syndrome, the increase of the range of motions in the knee joints, and the overall improvement of the quality of life. These beneficial changes persisted for a period of up to 6 months. CONCLUSION: The results of the present study give reason to recommend the proposed method of the remedial treatment for the wide practical application as a component in the framework of the medical rehabilitation programs. PMID- 26852501 TI - [The application of the combined resonance-wave therapy for the treatment of the patients presenting with chronic bacterial prostatitis]. AB - Recent studies have confirmed the anti-inflammatory and trophic effects of low intensity electromagnetic radiation with a frequency of 1 GHz in the microwave range in a number of inflammatory diseases. The results of experimental investigations demonstrating the influence of this physical factor on water molecules provide a basis for resonance-microwave therapy. Aim. The objective of the present work was evaluate the effectiveness of this physiotherapeutic method used for the treatment of 50 patients with chronic bacterial prostatitis (CBP). Patients and methods. All the patients were randomly divided into two groups. The main group included 26 patients, and the control group was comprised of 24 patients. The patients of the latter group were given only basic drug therapy, while those in the main group were additionally treated by means of resonance microwave therapy with the use of the Akvaton-02 apparatus (Russia). Dynamics of the clinical symptoms and the quality of life were evaluated based on the results of microscopic and bacteriological examination of the prostate secretion, measurements of the blood levels of tumor necrosis factor TNF-alpha and interleukin-1beta. RESULTS: The study has demonstrated that resonance-microwave therapy resulted in positive dynamics of pain and dysuric syndromes that was especially well apparent in the patients of the main group. This observation was confirmed by a significant change in the severity of the clinical symptoms of the disease estimated based on the NIH-CPSI scale and in the quality of life (QOL) of the patients. The microscopic and bacteriological examination of the prostate secretion revealed the pronounced anti-inflammatory and antibacterial effects in 19 (73.61%) patients of the main group compared with 16 (66.7%) patients in the control group. In addition, the low-intensity resonance-microwave therapy was shown to produce beneficial effect on the levels of pro-inflammatory cytokines in the blood of patients presenting with chronic bacterial prostatitis. The decline the TNF-alpha and IL-1beta blood levels was documented in the patients of both groups, but only in the main group the level of TNF-alpha was significantly different from its baseline value. In the majority of the patients, the above changes persisted for two months. CONCLUSION: The present study has demonstrated the increased clinical effectiveness of resonance-microwave therapy in the patients suffering from chronic bacterial prostatitis in comparison with baseline drug therapy and thereby confirmed the feasi bility of low-intensity electromagnetic radiation with a frequency of 1 GHz for the treatment of this pathology. PMID- 26852502 TI - [Ozonotherapy as an efficient component of the combined treatment of the patients presenting with bacterial vaginosis]. AB - The objective of the present study was to evaluate the effectiveness of the combined treatment of the patients suffering from bacterial vaginosis using various methods of ozone therapy. The comprehensive clinical and laboratory examination and treatment involved 102 patients of the child-bearing age divided into 3 groups, matched for the age and the main clinical manifestations of the disease. All the patients comprising group IlIl received basic therapy alone while the treatment of the patients of group I consisted of local ozone therapy and that of the patients of group 11 of the combination of local and general ozone therapy. The study has demonstrated the enhanced effectiveness of the combined local and general ozone therapy compared with the two other modalities and the feasibility of its application for the treatment of the patients presenting with bacterial vaginosis. PMID- 26852503 TI - [The application of laser therapy for the medical rehabilitation of the children presenting with chronic osteomyelitis]. AB - The objective of the present study was to develop a scientifically sound rationale for the application of infrared laser radiation (IRLR) either separately or in the combination with fluctuation magnetic therapy in the medical rehabilitation of the children presenting with chronic hematogenous osteomyelitis. Another objective was to evaluate the clinical effectiveness of this therapeutic modality. Two achieve these goals, the clinical observations and special research studies were conducted in two directions with the participation of 95 patients at the age varying from 1 to 15 years. The study has demonstrated the effectiveness of the inclusion of IRLR in the medical rehabilitation program for the children with chronic hematogenous osteomyelitis in different periods of the disease. It was shown that the transcutaneous infrared irradiation of the affected area during the exacerbation of chronic osteomyelitis had a well apparent immunostimulatory effect and reduced the activity of the inflammatory process. The application of IRLR in combination with fluctuation magnetic therapy during the period of partial remission, had a more pronounced influence on the microcirculation and stimulated the regenerative and trophic processes. PMID- 26852504 TI - [The safety of robotics for restorative medicine]. AB - The present article is devoted to the peculiarities of the safety measures that need to be taken during the operation of the automated robots intended to perform noninvasive controlled deformations of the patient's soft tissues. The authors propose the use of the commercially available devices for nonmedical applications operated without enclosure for staff as basic robots. PMID- 26852505 TI - [The necessity of new approaches to the elaboration of the projects for the sanitary (mountainous sanitary) protection districts around the therapeutic and health-promotion facilities, health resorts and their natural medical resources]. AB - The international experience gained during the past two centuries indicates that the most efficient and rational way to ensure the protection of the territories occupied by the therapeutic and health-promotion facilities, spa centres, and health resorts together with their natural medical resources is to set up sanitary (mountainous sanitary) protection districts or zones along the perimeter of these territories. Beginning from 2000, numerous changes and amendments have been annually introduced in the Russian legislation intended to ensure efficacious control over the rational exploitation of the territories of therapeutic and health-promotion value and their natural medical resources. These initiatives have negative effect on the activities of these organizations and the quality of the services they are expected to provide. Taken together these effects lead to the degradation of the spa and health resort business. Bearing in mind the current conditions for economic activities, it is proposed, in contrast to the former global approach, to envisage in the aforementioned projects the establishment of the sanitary (mountainous sanitary) protection districts or zones and determine their borders based on the results of the assessment of their potential for the protection of therapeutic factors and other valuable resources. Equally important is the maximum reduction of the areas of the second and third zones taking into account their relevant objective characteristics. In certain cases, the protective district may coincide with the second zone. As far as the federal health resorts and large territories of special health-promotion value are concerned, some of them may have two or more sanitary (mountainous sanitary) protection districts. Both the owners and the users of these territories should be provided the necessary and sufficient possibilities for the rational nature use at the grounds and in the adjacent water areas suitable for the development of health resort business in the conditions guaranteed by the national legislation. PMID- 26852506 TI - [The toxic complications of hydrogen sulfide-based balneotherapy in the spa and health resort practice]. AB - The present literature review was designed to consider the toxic complications of hydrogen sulfide-based balneotherapy encountered in the spa and health resort practice that should actually be regarded as hydrogen sulfide intoxication taking into consideration that their severity depends on the route through which the toxicant enters the body, its concentration in the therapeutic bath, and the overall duration of balneotherapy. Although such complications rarely occur in everyday practice, they may constitute a threat to the patient's health which implies the necessity of adequate measures for their prevention. PMID- 26852507 TI - MEGALENCEPHALY, POLYMICROGYRIA, POLYDACTYLY AND HYDROCEPHALUS (MPPH) SYNDROME: A NEW CASE WITH OCCIPITAL ENCEPHALOCELE AND CLEFT PALATE. AB - The megalencephaly, polymicrogyria, polydactyly, and hydrocephalus (MPPH) syndrome is quite rarely seen. The four main findings in this syndrome may be accompanied by severe psychomotor retardation, blindness, hypotonia, convulsions, and facial dysmorphism. In this paper, we present a female newborn at 39 weeks gestational age born to parents who are first degree cousins. Beside the facial dysmorphism and four main features of the MPPH syndrome, the findings on the physical examination of the patient were, hypertonicity, occipital encephalocele, cleft palate, and multiple polyps in the tongue. The presence of occipital encephalocele, cleft palate, and polyps in the tongue in this patient was not reported previously in the literature. PMID- 26852508 TI - A RETT SYNDROME CASE WITH NOVEL NON-IDENTICAL MUTATION IN MECP2 GENE. AB - The Rett syndrome (RTT; OMIM #312750) is a rare genetic disease observed predominantly among girls that affects neurological development. The incidence of this disorder is approximately 1 in 10,000 female births. Diagnosis of the RTT is based on specific clinical criteria and the identification of a mutation in the methyl-CpG-binding protein (MECP), which mainly occurs on exons 3 and 4 of the gene. Mutations in the X-linked methyl-CpG binding protein 2 gene (MECP2) are observed in nearly 95% of RTT cases. RTT is associated with considerable genotypic and phenotypic heterogeneity. Recently, it has been observed that mutations in the genes Netrin G1 and cyclin-dependent kinase like 5 (CDKL5) also lead to clinical pictures resembling RTT. In this case report, we describe a 4 years-old female patient who met all the relevant criteria for the diagnosis of RTT. Sequence analyses performed on the patient identified a de novo, heterozygous c.489G>A mutation at exon 4 of the MECP2 gene. PMID- 26852509 TI - CLINICAL REPORT OF A PATIENT WITH DE NOVO TRISOMY 12q23.1q24.33. AB - We report a patient with a rare de novo duplication of 12q23.1-12q24.33 region with a 32.7 Mb gain, having similar features seen in previously reported isolated cases of duplications of the 12q23q24 region, such as growth retardation, neuromotor retardation, corpus callosum agenesis, dysmorphic features such as, hypertelorism, epicanthus, flat nasal bridge, low-set small ears, down-turned corners of the mouth, micrognathia, cryptorchidism and limb anomalies such as pes plano valgus, prominent heels and overriding toes. Our patient has Noonan-like features, such as short stature, short neck, epicanthal folds, ptosis of eyelids, hypertelorism, pectus excavatum, widely spaced nipples and cryptorchidism. Duplication of PTPN11 gene has been postulated as a mechanism for the Noonan syndrome. Phenotypic features and the genes involved in this region are important to further delineate the 12q23q24 phenotype. PMID- 26852510 TI - A PATIENT WITH PARTIAL CHROMOSOME 12q DUPLICATION AND 10q DELETION. AB - Chromosomal deletions and/or duplications are relatively common cytogenetic abnormalities. Clinical findings depend on pure or complex forms of the anomaly, the location and size. In those cases, using current analytical technologies increases the possibility of discovering candidate genes that were not detected by conventional karyotyping responsible for these features. Here, we report an 18 month-old girl with prenatal and postnatal growth retardation, secundum ASD and PDA, facial dysmorphic features including frontal bossing, arched eyebrows, hypertelorism, wide nasal bridge and chronic diarrhea. Chromosome analysis on the peripheral leukocytes showed a 46,XX del(10)(q26.3),dup(12)(q24.11-q24.33) dn karyotype. An array-CGH analysis was performed to understand which genes were located on the deletion and duplication regions and what was their relationship with the phenotype. Based on our analyses, the deletion of the CALY gene on Chromosome 10q and the duplication of PTPN11 and TBX5 genes on chromosome 12q were possibly relevant for the clinical findings with our patient. PMID- 26852511 TI - CITRIN DEFICIENCY: AN INFANT INCIDENTALLY DETECTED BY PHENYLKETONURIA SCREENING WITH A NOVEL MUTATION IN SLC25A13 GENE. AB - We report the first Turkish patient with citrin deficiency detected incidentally by phenylketonuria screening. Mild cholestasis, increased alpha-fetoprotein level, aminoacidemia including citrulline and coagulation disorder suggested citrin deficiency. Screening the SLC25A13 gene revealed compound heterozygosity harboring a novel mutation, c.851-854delGTAT (p.M285Pfs*2)/ p.I290T (c.869T>C). Progression to type II citrullinemia was considered due to hyperammonemia episodes resulting from high carbohydrate/low protein diet. High protein/low carbohydrate diet resulted in cessation of hyperammonemia episodes, reversal of hepatic dysfunction and steatohepatitis. Our report illustrates the importance of awareness on citrin deficiency. PMID- 26852512 TI - RECURRENT RAB3GAP1 MUTATIONS IN THE TURKISH POPULATION. AB - Warburg Micro Syndrome (WARBM, MIM 600118) is a rare, severe autosomal recessive neurodevelopmental disorder characterized by microcephaly, microphthalmia, microcornea, congenital cataract, cortical dysplasia, corpus callosum hypoplasia, intellectual disability, hypotonia and hypogonadism. RABS, small G proteins belonging to the RAS superfamily, are master regulators of vesicle trafficking in the cell. The identification of mutations in the RAB3GAP1 and RAB3GAP2 genes, which together encode the RAB3GTPase-activating protein, a key regulator in calcium-mediated exocytosis of neurotransmitters and hormones, has underpinned abnormal development of the brain, eye and genitalia as cardinal features of this syndrome. More than 100 patients have been reported with WARBM, with mutations in the RABGAP1, RABGAP2, RAB18 and TBC1D20 genes. The objective of the study was to describe the recurrent RAB3GAP1 mutations and compare the clinical features of the patients with WARBM in the Turkish population. Here we report two brothers with Warburg Micro Syndrome 1 from a non-consanguineous Turkish family with clinical features similar to those previously reported in Turkish patients with RAB3GAP1 mutations. We found that the c.748+1G>A splice-site mutation in RAB3GAP1 intron 8 is common and has so far only been detected in patients of Turkish ethnic origin. Although one of our patients has a distal extra crease on the 4th finger and another has nephrolithiasis, there does not appear to be any specific phenotypic findings associated with this mutation. PMID- 26852513 TI - REVERSIBLE CLINICAL AND MAGNETIC RESONANCE IMAGING FINDINGS IN LATE-ONSET COBALAMIN C DEFECT. AB - Cobalamin C (Cbl C) disease is an inborn error of intracellular cobalamin metabolism. Two distinct clinical types are defined according to the age of onset. We describe an 8 year old girl with late-onset Cbl C disease presenting with neuropsychiatric symptoms. Mutation analysis revealed homozygous c.394C>T (p.R132X) mutation in the MMACHC gene. Serial magnetic resonance imaging (MRI) before and after the treatment are provided. MRI of the brain before treatment showed bilateral patchy focal hyperintensities in the white matter and cortical atrophy. After treatment with intramuscular hydroxycobalamin, oral folinic acid, oral betaine, normalization of MRI findings can be achieved in addition to clinical improvement. We present this case to draw attention to the reversibility of clinical and MRI findings in the late onset Cbl C disease after treatment. PMID- 26852514 TI - TWINS WITH KLEEFSTRA SYNDROME DUE TO CHROMOSOME 9q34.3 MICRODELETION. AB - Kleefstra or 9q subtelomeric deletion syndrome (9qSTDS) is a rare microdeletion syndrome. The most prominent phenotypic features include hypotonia, developmental retardation, as well as typical dysmorphic face. It has been shown that terminal deletions of the chromosome 9q34.3 region, or EHMT1 gene mutations, lead to Kleefstra syndrome. We present 16-month-old twin sisters, one of whom had originally been referred for Down syndrome screening due to hypotonia, growth and development retardation, dysmorphic facial signs, and accompanying congenital heart disease. They were subsequently diagnosed as Kleefstra syndrome based on subtelomeric FISH analysis. In conclusion, Kleefstra syndrome should be considered in the differential diagnosis of Down syndrome because it presents with very similar phenotypic features. PMID- 26852515 TI - OROFACIAL FINDINGS AND DENTAL MANAGEMENT OF WILLIAMS SYNDROME. AB - Williams Syndrome is a microdeletion syndrome characterized by a number of developmental and physical abnormalities. The aim of the present study was to evaluate the oral abnormalities and dental management of patients with Williams Syndrome. Fifteen patients with Williams Syndrome aged between 3-20 years old were evaluated in this study. Oro-facial findings, dental plaque index and DMFT/dmft scores were recorded in each patient. Panoramic radiographs and extraoral, intraoral photographs were taken from all patients. According to the results of this study, the mean DMFT and dmft scores were 0.39 +/- 0.12 and 1.81 +/- 0.39, respectively. The most common oro-facial findings were detected as high palate (87%), diastema (60%), failure to thrive (60%), feeding difficulties (60%), vomiting (47%), macroglossi (47%), microdontia (40%) and frenulum hyperplasia (40%). All decayed teeth were restored with compomer and composite restorations. In conclusion, dentists play a significant role for improving the quality of life of the patients with Williams Syndrome to minimize or prevent dental abnormalities. PMID- 26852516 TI - MEGALOCORNEA SHOULD BE INVESTIGATED IN CASES WITH HYPOTONIA AND MENTAL RETARDATION: NEUHAUSER SYNDROME--AN EASILY MISSED DIAGNOSIS. PMID- 26852517 TI - CHOANAL ATRESIA AND HIRSCHSPRUNG'S DISEASE ARE "LEGITIMATE" TRAITS OF DISTAL TRISOMY 4q. PMID- 26852518 TI - A CASE WITH 18q DELETION SYNDROME IDENTIFIED WITH B CELL ABSENCE AND CONGENITAL HEART DISEASE. PMID- 26852519 TI - A NEWBORN WITH OCULOCEREBROCUTANEOUS SYNDROME (DELLEMAN OORTHUYS SYNDROME). PMID- 26852521 TI - WAARDENBURG SYNDROME TYPE 1 AND A RARE FINDING OF ANAL ATRESIA. PMID- 26852520 TI - A NOVEL ASPARTYLGLUCOSAMINURIA MUTATION IN A PATIENT WITH CO-EXISTENCE OF GAUCHER DISEASE. PMID- 26852523 TI - [Revealing the structure of the nervous tissue III: From Jan Evangelista Purkyne (1787-1869) to Ludwig Mauthner (1840-1894)]. AB - The works of Jan Evangelista Purkyne, Gabriel Valentin and Robert Remak showed that the nervous system contains not only nerve fibers, but also cellular elements. The use of microscopes and new fixation techniques have enabled the retrieval of accurate data on the structure of nervous tissue and in many European universities microscopes began to be widely used for histological and morphological studies. The present review summarizes the discoveries of the structure of predominantly vertebrate nerve tissue during the period from 1838 to 1865, made by prominent scholars who described the structure of fibers and cells of the nervous system and demonstrated that some nerve fibers are enwrapped by a sheath. In addition, the first attempts were made to make a cytoarchitectonic description of the spinal cord and brain. During the same time the concept of a neuroglial tissue was introduced, first as a tissue for "gluing" nerve fibers, cells and blood capillaries into one unit, but later some glial cells were described for the first time. Microscopic techniques started to be used for examination of physiological as well as pathological nerve tissues. The overall state of knowledge was just a step away from the emergence of the concept of neurons and glial cells. PMID- 26852522 TI - PRENATAL ONSET DISSEMINATED RENAL VEIN THROMBOSIS EXTENDED INTO VENA CAVA IN A LATE PRETERM INFANT. PMID- 26852524 TI - [The role of adipose tissue in pathogenesis of type 2 diabetes mellitus]. AB - The incidence of metabolic diseases, mainly obesity, type 2 diabetes mellitus (T2DM) and cardiovascular diseases is significantly increasing. Worldwide it is spoken of emerging epidemics, even pandemics, of obesity and T2DM with serious health and socioeconomic impact. There is also a shift in incidence of metabolic diseases to younger age groups. These facts have emerged extensive research effort focused on deeper understanding and eventual therapeutic influence of insulin resistance (IR), the key moment in etiopathogenesis of T2DM. The pathogenesis of IR is very complicated and still not fully understood. Well known are environmental factors (lack of physical activity, energy-rich diet). Key player in development of IR is adipose tissue, mainly visceral adipose tissue (VAT). Disturbances of VAT metabolism and subclinical inflammation are considered as important factors leading to development of IR. VAT is producer of biologically active substances and pro-inflammatory cytokines that are linked to development of IR and T2DM as well. Another factor influencing formation of IR and function of pancreatic beta-cells is mitochondrial oxidative capacity together with oxidative stress. Discussed is being also the role of intestinal microbiome. PMID- 26852525 TI - [Methods for determination of cholinesterase activity]. AB - Cholinesterases hydrolyze acetylcholine and thus they play a key role in a process of cholinergic neurotransmission. Changes in their activities are linked to many diseases (e.g Alzheimer disease, Parkinson disease, lipid disorders). Thus, it is important to determine their activity in a fast, simply and precise way. In this review, different approaches of studying cholinesterase activities (e.g pH-dependent, spectrophotometric, radiometric, histochemical methods or biosensors) are discussed. Comparisons, advantages or disadvantages of selected methods (e.g most widely used Ellman's assay, extremely sensitive Johnson Russell method or modern technique with golden nanoparticles) are presented. This review enables one to choose a suitable method for determination of cholinesterase activities with respect to laboratory equipment, type of analysis, pH, temperature scale or special conditions. PMID- 26852526 TI - [Mitochondrial metabolism in mammalian spermatozoa--a minireview]. AB - Mitochondria are organelles producing macroergic compounds in basically all eukaryotic cells except mature erythrocytes. Mitochondria play an important role even in mammalian spermatozoa, in which mitochondrial ATP biosynthesis covers energetic demands connected with sperm movement (motility), maturation (including capacitation) and oocyte fertilisation. Mitochondrial localization and the existence of some specific mitochondrial-protein isoforms point at its indispensable role in fertility maintenance. Mitochondrial disorders are often manifested in tissues with high-energy demands (myopathy, neuropathy, cardiomyopathy), but mitochondrial dysfunction can be often detected also in other peripheral tissues and cells like spermatozoa. The main goal of this minireview is to summarize the most important findings about mitochondria producing cellular ATP supply and to present spermatozoa as a suitable and valuable biological material, which might be, despite of its uniqueness, a very useful material in clinical diagnostics of certain disorders including mitochondrial or neurodegenerative disorders. PMID- 26852527 TI - [The nutrition role of milk ceruloplasmin]. AB - Copper is an essential trace element for all aerobic organisms. In mammals, it is a structural and redox-based co-factor of the vital enzymes. Besides catalytic function, copper acts as a modulator of cell signaling ways. However copper ions outside the pre-organized coordination sphere can initiate the formation formation of reactive oxygen species through Fenton type reactions. Both deficiency and excess of copper lead to the development of the cardiovascular, neoplastic, and neurodegenerative diseases. In the present article the data on copper physiological functions as well as peculiarities of the mechanism of copper safe transport are briefly reviewed. Also the results of investigation of the mechanisms supporting copper homeostasis and mechanistic features of copper homeodynamics in the newborns are summarized. The data on molecular genetic mechanism of the mammary glands, which controls nutrition copper balance for newborns, are analyzed. The role of milk ceruloplasmin as the newborn's main source of nutritional copper is discussed. The quantity and quality of the baby formula copper-containing additives and their potential long-term health effects are considered. PMID- 26852528 TI - [Genomic, proteomic and metabolomic predictors of nonalcoholic fatty liver disease development in obese patients. Part I]. AB - The prevention, diagnosis and treatment of diseases associated to obesity require a qualitative increase of efficiency. There are still disputable questions about diagnostic significance of some molecules, including genomic, proteomic and metabolomic biomarkers. We observed 72 obese patients (20 men and 52 women, mean age--41.3 +/- 2.5) and performed ultrasound elastography and ultrasound of liver. We have identified two groups of patients: Group 1 consisted of 50 obese patients without complications (BMI 43.2 +/- 0.6), group 2 consisted of 22 patients with obesity complicated with nonalcoholic fatty liver disease (BMI 45.8 +/- 2.3). Determination of the adipokines (adiponectin, ghrelin, resistin, visfatin, and apelin), cytokine (interleukin--6, TNFalpha) oxidized lipoproteins (oxLDL), adhesion molecule sICAM (soluble intercellular cell adhesion molecule), fatty acid transporter L-FABP in serum was performed by ELISA. The study of the lipid metabolism involved determination of the concentration of total cholesterols, triglycerides, low and high density lipoproteins (LDL and HDL) by turbidimetry and spectrophotometry by analyzer. In addition, we conducted analysis of polymorphic alleles epsilon2, epsilon3, episolon4 of ApoE gene using polymerase chain reaction. Our data indicate that reducing the concentration of adiponectin (0.46-1.71 mcg/ml), increasing the level of glucose (5.57-6.25 mmol/l), triglycerides (2.06-3.94 mmol/l), TNFalpha (5.07-16.68 pg/ml) and L-FABP (11.62 23.76 pg/ml) are predictors of nonalcoholic fatty liver disease in obese patients, and the presence of genotype epsilon3/epsilon4 of ApoE gene is a poor prognostic marker of severity of nonalcoholic fatty liver disease. PMID- 26852529 TI - [Features of dietary treatment in patients with coronary heart disease]. AB - The present review summarizes the current data of dietary treatment in patients with coronary heart disease (CHD). Numerous studies have shown that the diet can affect the modifiable risk factors for CHD that is the basis of primary and secondary prevention of this disease. The main areas of personalization of nutrition is the selection of an adequate energy value, a certain quota of protein,fats and carbohydrates in the diet, as well as other micronutrients that may influence the development of coronary artery disease. Caloric restriction of the diet in overweight patients is the most important factor of weight loss, independent of macronutrient composition of the diet. Diets with higher dietary protein content increase the rate of weight loss and improve blood lipid profile, but have a short-term effect. Excessive consumption of saturated fatty acids is associated with increased risk of cardiovascular disease. As a result, numerous studies have shown that replacing saturated fats with mono- and polyunsaturated fatty acids have a beneficial effect on blood lipid profile in patients with coronary artery disease. Several studies have shown that increasing the glycemic load is accompanied by an elevated risk of CHD, especially in women. Personalized dietary treatment on the basis of the etiopathogenic mechanisms of CHD and with the individual characteristics of a particular patient (sex, age, heredity, nutritional status, physical activity) is becoming increasingly important. Personalization of the diet provides a positive effect on risk factors for coronary heart disease, on the quality of life and increases the effectiveness of diet-therapy. PMID- 26852530 TI - [Low calorie diet influence optimization on body composition at obese patients with secondary diastolic heart failure]. AB - In open prospective monocentric study in 3 parallel groups we studied the effectiveness of correction of body composition using low calorie diet therapy with inclusion of specialized food products (SFP)--sources of polyphenols and iridoids made on the basis of the juice of Morinda citrifolia L. fruits. We studied 90 patients aged from 30 to 50 years old with grade III obesity and clinically expressed secondary diastolic heart failure. The duration of diet therapy was 42 days. It was shown that low-calorie diet has non-optimal effect on the body composition in morbidly obese patients with secondary diastolic heart failure, namely leading to the expressed loss of body fatless (7.2%, p=0.00008) and muscle mass (by 16.6%, p=0.00004); at the same time the reduction of total body weight is noted only by 2.3% (p=0.053), reduction of waist measurement by 1.3% (p=0.028) and reduction of hips measurement by 1.3% (p=0.09), accompanied by the reduction of body fat by 8.5% (p=0.000017) and of liquid by 7.3% (p=0.0018). The introduction of the SFP into the diet optimizes the effect of low calorie diet therapy on the anthropometric parameters and body composition. The most important effect of the SFP is the ability to prevent the excess loss of muscle mass in patients, and this effect is being dose-dependent. The loss of muscle mass in two groups of patients was 3.1-4.1% after 6 weeks of diet therapy, while in the control group it was 8.5% (p=0.0051). We have concluded that the inclusion of the SFP, manufactured on the basis Morinda citrifolia L. (noni) juice to the low calorie diet allows to initiate mainly the loss of the body fat with the simultaneous protection of active cellular mass, which is without doubt can be considered as the advantage compared to the standard low calorie diet. PMID- 26852531 TI - [Body mass index and other anthropometric parameters of the physical state in relation with age and individual-typological specific of women constitution]. AB - The physical state of body construction of 651 practically health women 20-55 years old were studied by using a complex of anthropometric and bioelectric methods (conditional norm, slavonians, inhabitants of Moscow region). The leptosome constitutional group was established in 152 cases (23.3%), mesosome group was exposes in 259 cases (39.8%), megalosome group was revealed in 189 cases (29.0%) and indeterminate group was fixed in 78 cases (8.0%). Women of mesoplastic somatotype were established in 26.9%, sthenoplastic somatotype--in 16.7%, picnic somatotype--in 13.7%, subathletic somatorype--in 11.5%, euriplastic somatotype--in 12.3%, athletic somatotype--in 5.2% and asthenic somatotype--in 1.7%. Sizes and weight parameters were depending on type of women body construction. Norm of body mass index for asthenic women was fixed as 16.9; for sthenoplastic somatotype--20.3; for athletic somatotype--23.1; for subathletic somatotype--24.2; for mesoplastic somatotype--24.6; for euriplastic somatotype- 24.7; for picnic somatotype--26.2. The length of women body was varied from 158.2 +/- 0.5 (152.0-165.0) cm for sthenoplastic somatotype and 159.6 +/- 0.4 (152.0- 164.8) cm for mesoplastic somatotype to 169.4 +/- 1.7 (162.2-187.4) cm for athletic somatotype. Body weight was also in correspondence with type of constitution. It was 47.8 +/- 0.6 (44.2-54.6) kg for asthenic somatotype, 50.6 +/ 0.4 (42.6-54.2) kg for sthenoplastic somatotype, 62.2 +/- 0.2 (56.3-64.9) kg for mesoplastic somatotype, 68.6 +/- 0.7 (64.5-82.7) kg for picnic somatotype, 66.2 +/- 1.0 (62.0-76.5) kg for athletic somatotype, 68.2 +/- 1.0 (63.4-76.5) kg for subathletic somatotype and 75.0 +/- 1.0 (68.4-92.5) kg for euriplastic somatotype. Mass of bone component was minimal for women of picnic somatotype (6.4 +/- 0.1 kg) as well as asthenic somatotype (7.3 +/- 0.3 kg) and maximal for subathletic (9.3 +/- 0.1 kg) and euriplastic (9.4 +/- 0.1 kg) somatotypes. Skeletal muscles mass was varied from 18.7 +/- 0.4 kg (asthenic somatotype) to 30.2 +/- 0.4 kg (athletic somatotype). Fat tissue mass was varied from 7.0 +/- 0.2 kg (asthenic somatotype) to 32.2 +/- 0.2 kg (euriplastic somatotype). There were established intercommunications between women constitutional characteristics and pecualiarities of their body construction. PMID- 26852532 TI - [Toxicological assessment of nanostructured silica. III. Microecological, hematological indices, state of cellular immunity]. AB - This paper is the third in a series of publications on the experimental study of subacute oral toxicity of nanostructured silicon dioxide (SiO2). We used commercial nanostructured SiO2, obtained by hydrolysis of tetrachlorosilane in the gaseous phase, with the size of the primary nanoparticles (NPs) of 5-30 nm. The aqueous dispersion of SiO2 after treatment with ultrasound was administered to rats with initial weight of 80 +/- 5 g for the first 30 days by intragastric gavage and further for 60 days with diets in doses of 0.1; 1.0; 10 and 100 mg/kg body weight per day. Animals of the control group were treated with deionized water. The amount of basic and transient populations of gut microbiocenosis, hematological indexes were measured using standard methods. Specific content of the B-lymphocytes (CD45RA+), total T-lymphocytes (CD3+), T-helper cells (CD4+), T cytotoxic cells (CD8+), NK-cells (CD161a+) in general population of lymphocytes was evaluated byflow cytometry; serum cytokine levels of TNF-alpha, IL-6, IL-10 were determined by ELISA. No significant changes in the qualitative and quantitative composition of the intestinal microbiota populations regardless of the dose of administered nanomaterial have been found. This gave reason to believe that the postulated mechanism of the toxic effects of the NPs of SiO2, mediated by modification of the composition of the intestinal microflora and the corresponding changes in its functional activity, apparently, is not realized. The main target of nanostructured SiO2 was the T-cellular system of the immune system of animals, that was manifested in the significant decrease of the number of leukocytes (33%), number of T-helper cells (13%), CD4/CD8 ratio (27%) and increasing the number of cytotoxic lymphocytes (19%) and the level of TNF-alpha (590%). The value of the maximum dose (NOAEL) of nanostructured SiO2, has no effect on T-cell immunity was not more than 100 mg/kg body weight per day. PMID- 26852533 TI - [Analysis of antioxidant status and actual diet of students]. AB - The study of the features of the antioxidant status and dietary intake of students is highly relevant, since this population cohort is the future labor potential of society. 40 female students (mean age--22.4 +/- 0.6 years) living in hostel dormitories (n=20) and rented apartments (n=20) were surveyed. To assess the nutrition the method of questioning within 5 days, including weekends has been used. Personal energy consumption per diem has been calculated by table keeping method. It was found that, retinol blood serum content (measured spectrofluorimetrically) in students living in dormitories was 1.45 fold lower than that in students living in rented apartments (1.28 +/- 0.66 vs. 1.86 +/- 0.17 mmol/l, p<0.001). When analyzing the changes of the integral parameter of antioxidant defense system (the total antioxidant activity assessed using as a model system a suspension of egg yolks lipoprotein) a decrease of this parameter with respect to standards for the majority of the surveyed women (65% of students living in dorms and 80% of students living in rented apartments) has been noted. The energy value of the daily ration for girls in both groups (1375 +/- 626 kcal- in a dormitory and 1731 +/- 547 kcal--in a rented apartment) was lower than energy expenditure (1789 +/- 202 and 1808 +/- 234 kcal/day, respectively), with higher energy value in students living in rented apartments (p<0.001). Carbohydrates prevailed in the diet of students living in dormitories (417 +/- 207 g/day vs. 289 +/- 131 g/day in female students living in rented apartments, p<0.0001) while in the diet of the students living in rented apartments fats (110.5 +/- 55.7 g/day, compared with that of the students living in the hostel- 66.1 +/- 50.8 g/day, p<0.0001) and proteins (99.1 +/- 47.9 vs. 81.6 +/- 42.7 g/day, p<0.001) prevailed. Thus, the high-risk group with regard to adaptive capacity and unbalanced diet are students living in dormitories, with a crucial role played by low material support. PMID- 26852534 TI - [The study of rs1800012 polymorphism of the alphal-chain collagen type 1 gene in Moscow women and children with different level of bone strength]. AB - The frequency of rs1800012 polymorphism of alpha1-chains of type 1 collagen gene (COL1A1) was studied by real-time PCR in 422 Moscow women and children, including pregnant women (n=96), lactating (n=29) and non-pregnant women (n=28) and preschool children (2-6 years, n=76) and school children (7-16 years, n=193) with different levels of bone strength (BS) as determined by ultrasound densitometry. It was found that the decrease in the value of the BS (Z-score < -1) was observed in 60% of women, 54% of preschool children and 48% of school-aged children. In the surveyed cohort the predominant genotype of rs1800012 polymorphism CO1A1 geneI gene was GG (55.1%), the frequency of the genotype TT--7.6%, of T-allele- 26.2%. There were no statistically significant relationships of BS with a particular genotype of rs1800012 polymorphism 1f1COLIAI gene in all examined women. A positive but not statistically significant association of T allele with a risk BS reduction was found in non-pregnant and pregnant women (OR=2.143, p=0.31 and OR=1.227, p=0.55, respectively). For preschool and school-aged children T allele was not associated with the risk of BS reduction. In school-age children a statistically significant inverse association of T allele with the risk of BS reduction was shown (OR=0.621 wth PMID- 26852535 TI - [Features of food priorities in urban population of Kazakhstan in regard of consumption of foods with high glycemic index and significant content of fat]. AB - The diseases, associated with metabolism disorders, are now considered as the most common in the world, their prevalence has reached epidemic indicator values in both developed and developing countries. One of the most important methods of treatment and correction of dyslipidemic disorders and disorders of carbohydrate metabolism is the changing of eating behavior, including the literacy of consumers when choosing foods. The most significant indicators of the value of products for patients with metabolic disorders are the glycemic index and fat content. The frequency of consumption of foods with high glycemic index and significant content of fat in urban population of Kazakhstan has been investigated. A random, stratified by sex and age sampling from the number of residents (n=8219) of large cities of Kazakhstan at the age of 18-73 years has been covered. The study was performed using a specially designed questionnaire, including detailed questions on assessment of eating behavior, eating habits and diet. It has been revealed that foods with a high glycemic index and significant fat content are the predominant in frequency of consumption by the urban population of Kazakhstan. About 90% of the citizens consumed bread and bakery products daily or several times a week. Pies, cakes and cookies are consumed daily or several times per week by 35% of the surveyed, pasta products--57%, cereals--68% of the urban population. Average daily diet of fruit and vegetable set of urban residents of Kazakhstan represented 80% of the potatoes, carrots and beets. Tea and coffee admission is traditionally combined with the intake of sugar and sweets. More than 70% of surveyed population consume butter daily or several times a week. The excessive intake of foods with a large amount of fat and high glycemic index against the background of the deficiency of complete protein remains an urgent problem for several years. The obtained results dictate the need of development and implementation of targeted regional programs for continuous instruction of the population on healthy nutrition basics with the ultimate goal to improve the health of the population of the Republic as a whole. PMID- 26852536 TI - [Comparative characteristics of the isotopic D/H composition and antioxidant activity of freshly squeezed juices from fruits and vegetables grown in different geographical regions]. AB - Data presented in this paper reflect changes in antioxidant activity, the content of prooxidant factors and deuterium concentration in freshly squeezed juices from fruits and vegetables grown in different climatic regions (10 samples of juices from wholesale and retail trade network of 8 kinds of vegetables and fruits, 28 manufacturers from 14 countries). Determination of the concentration of deuterium was performed using a nuclear magnetic resonance spectrometer. Total antioxidant activity of fresh juices was determined amperometrically after dilution in 2.2 mM H3PO4 in a ratio of 1:100. Prooxidant performance was evaluated by a maximum and area of flash of chemiluminescence induced by the introduction of 0.3% hydrogen peroxide. It was found that the antioxidant activity of fresh juice from fruits and vegetables grown within the same climatic region can differ by several times. In this case, most of the fruits and vegetables of russian producers were not inferior, than antioxidant activity of the fresh juices from the same plant products grown abroad. It should be noted that the indicators of the antioxidant activity of fresh juice from Russian pears exceeded this indicator of all fresh juices from pears, imported from Argentina, South Africa and the United States of America by 21.1, 30.4 and 32.7%, respectively. In assessing the prooxidant properties of fresh juices should be noted the almost complete absence of factors with prooxidant nature only in 36% of the studied fresh juices, whose maximum performance and area of flash of chemiluminescence were less than 0.1%, including a pear and apple juices from the russian production. It should be noted that the area of chemiluminescence of the juice from potatoes, grown in Russia, was at 103.1 and 115.2% lower than in juice obtained respectively from potatoes produced in Israel and Egypt (p<0.05), indicating a higher safety of consumption of potatoes produced in Russia. When studying--the isotopic D/H composition of fresh juices it was found that the highest deuterium content was in the juice from the pears, imported from Argentina (deltaD = -72% per hundred), while the lowest concentration of deuterium was observed in the juice from the Egyptian potatoes (delta = -358% per hundred). In general, significantly lower deuterium content was determined in fresh juices made from potatoes and cabbage grown in different countries, in comparison with other fresh juices from fruits and vegetables. The smallest range of differences in the isotopic D/H was composed in freshjuices from tomato, pomegranate and oranges of Turkish manufacturers (deuterium concentration ranged in them from -221 to -214% per hundred), that can be used to confirm the geographical origin of fruits and vegetables grown in Turkey. The data reflecting the antioxidant activity, the content of prooxidant factors and deuterium concentration in the juices, allow us to recommend the latter as additional criteria when assessing the quality of food products. PMID- 26852537 TI - [The study of the peculiarities of metabolism in individuals with rs9939609 polymorphism of FTO gene]. AB - A total of 104 people, among them were 18 men and 86 women aged 18 to 67 years- people in the Moscow region of the Russian Federation, in the sanatorium treatment. Association embodiment rs9939609 FTO obesity was studied using allele specific amplification, detection results in real time using TaqMan-probes complementary DNA polymorphisms. The frequency of the mutant allele in individuals was 47.0%, while the TT genotype was detected in 25.0% of cases, AT- in 56.0%, AA.0%. In men, prevalence rates of obesity risk allele (A) is higher than in women. In individuals with obesity (BMI over 30 kg/m2) indicated the presence of more AA genotypes (2 7.8%) compared to individuals with a body mass index of less than 30 kg/m2 (14.1%) and a high frequency of occurrence (54.2 versus 43.0%) risk allele A. Compared with individuals with genotype TT, the examinees with the AA genotype rs9939609 FTO gene was significantly higher BMI, waist circumference, hip circumference, fat mass. The same patients energy expenditure at rest value, calculated per kg of lean body mass or muscle, was slightly less than with TT genotype. In individuals with the AA genotype rs9939609 FTO gene compared with the TT genotype had significantly lower levels of HDL cholesterol and serum iron in the background significantly elevated concentrations of uric acid. Thus, the evaluation of patients with the use of innovative technologies in a spa treatment allows their personal alimentary correction for the prevention and treatment of non-communicable diseases. PMID- 26852538 TI - [Evaluation of sufficiency with vitamins C, B1 and B2 of newborn infants feeding different types of nutrition, by means of urinary excretion determination]. AB - With the help of non-invasive methods the sufficiency with vitamins C, B1 and B2 in 58 newborns (38-40 weeks of gestation) on breastfeeding as well as on mixed or artificial feeding has been evaluated. Urinary excretion and breast content of ascorbic acid (measured by visual titration), thiamin (by thiochrome fluorimetric method) andriboflavin (fluorimetrically by titration with riboflavin-binding protein) was determined on the 3-10th day after birth. 35 infants were exclusively breastfed. 40% of their mothers regularly took multivitamin supplements during pregnancy and 42.9%--both during pregnancy and after childbirth, 17.1% did not use vitamin complexes either duringpregnancy or after childbearing. The content of vitamins C, B1 and B2 in the breast milk of women who did not additionally intake vitamins during pregnancy and lactation, was reduced compared with that of mothers who took multivitamin supplements, and provided only a half of the needs of their child in these vitamins. All these babies have urinary excretion of vitamins below the lower limit of norm. Among infants whose mothers took multivitamin supplements during pregnancy, but stop taking them immediately after their birth, only 28.6% of newborns were provided with vitamin C, while all the children identified a lack of vitamins By and B2. The insufficiency with vitamins C and B1 was detected in one third of children breastfed by mothers who took vitamins during pregnancy and continued intaking them after birth, adequate supplied with vitamin B2 was 35.7% of the surveyed. Determination of vitamin urinary excretion (perg creatinine) is useful for vitamin status evaluation. The content of vitamins in breast milk can be used for assessment of vitamin status both a nursing woman and her child. Taking into consideration that the diet of a breastfeeding woman is not always the best, there is no doubt about the need to continue multivitamin intake during breastfeeding. The question on the doses of vitamins in vitamin-mineral supplements for lactating women, providing vitamin content of breast milk at an optimal level, or intended specifically for infants, nowadays is extensively discussed. PMID- 26852539 TI - [Nutrition and biological value of food parts of a trade bivalve mollusk Anadara broughtoni]. AB - Currently, the human diet includes different new products of seafishing, including non-fish--bivalves and gastropods, holothurias, echinoderms, jellyfishes that demands careful studying of their chemical composition. The purpose of the study was to determine the nutritional and biological value of all soft parts of the burrowing bivalve MOLLUSK Anadara broughtoni from the Far East region. It was established thatfood parts of a bivalve were significantly flooded (water content--73.5-84.2%), with the minimum water content in the adductor and maximum in the mantle. Dry solids are presented by organic (89-93%) and mineral (7-11%) components. Organic components consist of protein (14.6-20.7%), lipids (1.8-2.3%), carbohydrates (2.1-2.6%). The analysis of amino-acid composition of proteins of food parts of the mollusk of Anadara broughtonishowed the presence of all essential amino acids with slight differences in their content depending on the localization of the protein. All edible parts have tryptophan as the limiting amino acid. Muscle proteins have maximum level of lysine, methionine, cysteine, phenylalanine and tyrosine; mantle proteins--leucine, isoleucine and threonine; adductor proteins--valine, phenylalanine, tyrosine, methionine and cysteine. Predominant nonessential amino acids forproteins of all food pieces are glycine, aspartic acid, glutamic acid, arginine. The coefficient of amino-acid score differences of adductor protein (31.7%) is less than the same of cloak by 3.7%. The indicator "biological value" is maximal for adductor (68.3%), but the differenceformuscle is only 0.83%. Mantle proteins are characterized by minimum biological value (64.6%). The coefficient of utility of amino acid composition of protein is maximalfor muscle (57.83%), and values for a cloak and an adductor differ slightly (55.81 and 55.96%). Taurine content in food parts of a mollusk Anadara broughtoni is rather high compared to with other bivalve mollusks of the Far East region. Muscle tissue has maximal content of taurine (569.3 +/- 28.2 mg/100 g wet tissue), adductor occupies an intermediate position (387.9 +/- 18.2 mg/100 g wet tissue) and the minimum content of this amino acid is characteristic for mantle (297.1 +/- 13.4 mg/100 g wet tissue). PMID- 26852540 TI - [Caffeine in nutrition. Article 1. Consumption with food and regulation]. AB - The article presents a review of the literature data on the effect of caffeine contained in a variety of foods on the functions of human, it presents the modern international legal regulatory rules in the consumption of caffeine, and caffeine consumption rules corresponding to the technical regulations of the Customs Union (Russian Federation, Kazakhstan, Belaruss). It describes the sources of caffeine in the traditional diet and its consumption, safety evaluation in connection with the acute and chronic caffeine consumption and the value of caffeine as an ingredient in soft drinks tonic. PMID- 26852542 TI - How Will You Be Remembered? It is your responsibility to leave your EMS organization better than you found it. PMID- 26852541 TI - Repetitive Risks. For this EMS crew, unloading the stretcher proved dangerous to both patient and provider. PMID- 26852543 TI - How to measure and improve EMS systems. EMS Compass is setting the profession on a path toward performance measurement and improvement. PMID- 26852544 TI - Evidence-Based EMS: Out-of-Hospital BiPAP vs CPAP. Is one any better than the other? PMID- 26852545 TI - ACE INHIBITOR-RELATED ANGIOEDEMA: What You Probably Didn't Learn in Paramedic Training. ACEI-RA is a different beast, less than responsive to standard pharmacological agents. PMID- 26852546 TI - Oxygenate and Resuscitate Before You Intubate. Common pitfalls to avoid when managing the crashing airway. PMID- 26852547 TI - Community Paramedics and the Drug-Seeker. Beyond pain, emotional and psychological needs can help drive pseudoaddictive behaviors. PMID- 26852548 TI - When SIZE Matters: Offshore Helicopter EMS Operations. Providing medical and resue services to the offshore oil industry is a massive mission. PMID- 26852549 TI - Find Your "Next". What would you do if you could no longer work in the field? PMID- 26852550 TI - [The eye, the crossroads to humanity]. PMID- 26852551 TI - [Eye and the environment]. AB - The eyes are exposed to multiple environmental factors, which affect visual development, comfort, and visual health. While overexposure to sunlight can cause ocular surface and retinal pathologies, insufficient exposure to daylight could significantly contribute to myopia progression. New artificial lights, namely LED, have a higher risk of retinal phototoxicity, and could alter ocular circadian rhythm. The significant increase of prevalence of ocular allergies could be caused by the proliferation of environmental polluting substances, like tobacco smoke, fuel combustion by-products, or phtalates, which are found in many types of plastics. Finally, some dietary supplements could play a protective role in certain types of ocular pathologies, namely retinal pathologies. PMID- 26852552 TI - [Hypertension and the eye]. AB - Systemic hypertension is widely spread in the general population. It is recognised as a major risk factor for cardiovascular morbidity and mortality. Hypertensive retinopathy is the most common manifestation. Initial changes are retinal arteriolar vasoconstriction and findings such as flame or blot hemorrhages, cotton wool spots and hard exsudates resulting from localised retinal ischemia. Ocular complications of high blood pressure (HBP) are subconjunctival hemorrhages and retinal vein occlusions. Hypertensive retinopathy contributes to worsening of diabetic retinopathy. Less common but more threatening are ischemic optic neuropathy and retinal arterial occlusions. Screening is recommended in case of severe systemic hypertension, diabetes, or any complain of recent visual disturbances. PMID- 26852553 TI - [Drug-induced toxicity and ophthalmology]. AB - Affecting primarily the anterior part of the eye, all the structures of ophthalmological body may however be reached in case of drug- induced toxicity: eyelids and the conjunctiva for example in the syndromes of Lyell and Steven Johnson, cornea with cornea verticillata related to amiodarone, ciliary muscle (accommodation) or pupil related to antidepressants, lens with glucocorticoid induced cataract, retinal toxicity of anti malarial synthesis or optical neuropathy with ethambutol. Unfortunately often underrated because of their usual benignity, drug side effects affecting the eye yet can be severe. Simple, conscientious and planned monitoring however allowes for a large majority of our patients to minimize the risk of visual function impairment, thus preserving optimal visual function over time. PMID- 26852554 TI - [The management of diabetic retinopathy and diabetic macular edema; joint forces fight for sight]. AB - Despite the considerable progress in prevention and treatement options since the first big epidemiologic studies in the 80's, diabetic retinopathy still represents the primary cause of blindness in the working age population. The intensified prevention efforts that took place recentyears did show hopeful results as the incidence of diabetic retinopathy seems to decline. However a still considerable number of patients does not meet metabolic or treatment recommandations. In the aftermath of an ongoing globalisation and growing urbanisation of the society, there is an even bigger need of understanding the disease as well as improving prevention and treatment guidelines. PMID- 26852555 TI - [Optic neuritis: diagnosis, treatment and clinical implications]. AB - Optic neuritis is one of the most important causes of visual loss in young and middle aged adults. The prognosis in terms of functional outcome is good. The diagnosis of optic neuritis is a clinical one. Steroids can shorten the recovery time but do not change the long term functional outcome. The MRI is the most important investiga- tion to assess an associated risk of multiple sclerosis. Optic cohe- rence tomography (OCT) contribute additional details to course and functional outcome of optic neuritis. In the future the OCT may additionally contribute to the relationship between optic neuritis and possible associated multiple sclerosis. PMID- 26852556 TI - [The eye and cancer]. AB - Cancer involves so rarely the eye that it may be recognized late. The most frequent primary intra-ocular tumours are retinoblastoma in small children and uveal melanoma in adults. Vision loss in systemic cancer has a varied differential diagnosis. Uveal metastases are most often associated with breast cancer, but can herald lung carcinoma. Masquerade syndrome looks like inflammation but represents the ocular involvement of primary CNS non-Hodgkin lymphoma. Systemic cancer drugs, as well as radiotherapy, can cause ocular toxicity, mostly at the retina. In the rare paraneoplastic syndromes, patient's cancer antibodies cross-react with retinal antigens, leading to severe vision loss. When cancer involves the eye, a fast referral into specialized care can significantly improve visual and vital prognosis. PMID- 26852557 TI - [Biomonitoring information management and communication: an ethical and interdisciplinary perspective]. AB - This study explores biomonitoring communication with workers exposed to risks. Using a qualitative approach, semi-directive interviews were performed. Results show that occupational physicians and workers share some perceptions, but also point out communication gaps. Consequently, informed consent is not guaranteed. This article proposes some recommendations for occupational physicians' practices. PMID- 26852558 TI - [Fasting and chemotherapy: what do we tell our patients?]. PMID- 26852559 TI - [Neuromuscular diseases: is it necessary to make a choice for gene therapy?]. PMID- 26852560 TI - [FORTUNATE DOCTORS?]. PMID- 26852561 TI - [New antitubercular agents are not where where we need them to be]. PMID- 26852562 TI - [A clinical score predictive of meniscal tears?]. PMID- 26852563 TI - [Miscellaneous: penis transplants, malaria and electronic cigarettes]. PMID- 26852564 TI - [Electronic patient records: Switzerland is moving forward haphazardly]. PMID- 26852565 TI - [Division between base and complementary insurance: definitive refusal of Parliment]. PMID- 26852566 TI - [Consolation]. PMID- 26852567 TI - U.S. SLAVERY AND THE BLACK RADICAL TRADITION: THE 25TH ANNIVERSARY EDITION OF STERLING STUCKEY'S SLAVE CULTURE. PMID- 26852568 TI - [Assortative mating and maintenance of intrapopulation polymorphism in wild populations and laboratory cultures of insects]. AB - Speciation as a micro-evolutionary process begins with emerging of intraspecies differentiation, which is associated with establishment of reproductive isolation. One of intrinsic isolation factors ensuring physiological isolation is assortative mating. In course of long-term field observations in the Southern Urals (Republic of Bashkortostan) and prolonged laboratory experiments, we have detected assortative mating in populations of potato beetle Leptinotarsa decemlineata Say (Coleoptera: Chrysomelidae). Three morphotypes were singled out by the extent of integument melanization, namely achromists (A), melanists (M), and intermediate type (I), and frequency of occurrence of these morphotypes imago pairs significantly deviated from random distribution, thus manifesting the assortative mating. Under in copulo conditions, mating between achromist males (A) and melanist females (M) where active choice belonged to males was not registered. In.laboratory experiments, in the sample of 40 artificially formed pairs, there were detected significant differences in longevity and fecundity of different morphotype imagoes. Achromists and melanists had significantly (almost two times) higher longevity as compared with intermediate type. Females of intermediate type were significantly more fecund in homonomous crossings than achromists and melanists. It is shown that pairs offspring also differs significantly in viability, with highest viability being characteristic for offspring from females of A- and I-type. The differences revealed are indicative of different reproductive strategies that exist in populations. In laboratory line S of house fly Musca domestica L. (Diptera: Muscidae) the presence of individuals with different reproductive strategies related to longevity is detected. Maximum longevity in inbred lines Sh28 (short living) and L2 (long living), isolated from the line S, significantly differed almost twofold. In the line of short living flies, mass reproduction occurs on the first-second week of imago stage, while in long living flies it is put off to the third-fourth week. In reciprocal crossings between the lines, drastic reduction in females fecundity is observed as well as reduction in viability of females from hybrid offspring. The results obtained are indicative of substantial role of assortative mating and frequency-dependent selection in maintenance of intrapopulation diversity. PMID- 26852569 TI - [Maternal effect obscures adaptation to adverse environments and hinders divergence in Drosophila melanogaster]. AB - Adaptation to contrasting environments can facilitate ecological divergence and sympatric speciation. Factors that influence the probability and tempo of these processes are poorly known. We performed an evolutionary experiment on Drosophila melanogaster in order to attain better understanding of adaptation dynamics and to model the initial steps of sympatric speciation. In our experiment, several populations are being cultured either on standard rich medium (RM) or on nutrient deficient starch-based medium (SM). After 10 generations, experimental populations demonstrated unexpected changes in their fitness: on the starch medium, flies grown on RM (FRM) outcompeted those that were cultured on SM (FSM), while on the rich medium, FRM were outcompeted by FSM. That is, experimental populations demonstrated higher fitness on the foreign medium, but were outcompeted by the aliens on the one they had been accustomed to. To explain the paradox, we hypothesize that the observed low fitness of FSM on SM was due to maternal effect, or the "effect of starving mother". The FSM flies are probably better adapted to SM, but the phenotypic outcome of their adaptations is obscured because the females grown on the poor medium invest less in their offspring (for instance, they may produce nutrient-deficient eggs). Larvae hatched from such eggs develop successfully on the rich medium RM, but experience delayed growth and/or lower survival rate on the nutrient-deficient medium SM. To test the hypothesis, we measured the fitness of the flies FSM after culturing them for one generation on RM, in order to remove the assumed maternal effect. As expected, this time FSM demonstrated higher fitness on SM compared to control flies (FRM) and to FSM before the removal of the maternal effect. The results support the idea that non-adaptive phenotypic plasticity and maternal effects can mask adaptation to adverse environments and prohibit ecological divergence and speciation by allowing the migrants from favourable habitats to outcompete resident individuals in adverse ecotopes despite the possible presence of specific adaptations in the latter. PMID- 26852570 TI - [Polyvariant ontogeny in woodreeds: Novel models and new discoveries]. AB - Polyvariant ontogeny (PVO) is expressed visually in the life cycle graphs (LCGs) for Calamagrostis woodreeds as a variety of pathways for individual plants to develop through many of their states distinguishable by the ontogenetic stage and chronological age (in years). PVO is recognized as the basic mechanism of adaptation in local plant populations to their environments, while they find a quantitative measure of the adaptation via developing a matrix model of double structured population, calibrating the matrix of vital rates from empirical data, and calculating its dominant eigenvalue lambda1. This approach encounters an obstacle typical for rhizome grasses: while the rates of aging and ontogenetic transitions can be deterinined from field data mainly by the morphology of aboveground parts of the plant, the rates of vegetative propagation can be reliably determined only from digging up the belowground rhizome system, i.e., by destroying the sample plot ('reproductive uncertainty'). Therefore, the former (non-destroying) calibrations of matrix models were subjective to an extent, resulting in correspondingly subjective estimations. A novel method to overcome the 'reproductive uncertainty' makes use of the maximation hypothesis: the uncertain rates are such that lambda1 attains its maximal possible value under the given conditions. To test the hypothesis, we have conducted a field experiment by a new technique with a model species, the woodreed Calamagrostis epigeios (L.). Roth, that reproduces vegetatively in a meadow phytocoenosis and a spruce forest clearance. Excavating the whole system of ramets with their rhizomes and analyzing the maternal-child links in the laboratory have provided for (in addition to the former data on the local population structures and ontogenetic transitions) a new kind of data to calculate the status-specific rates of reproduction. The novel method of calibration has enabled us to find an exact range of lambda1 values, i.e., the true quantitative bounds of adaptation for a given local population. Obtained under the reproductive uncertainty and maximation hypothesis, the values of lambda1 have turned out close to the upper bounds of the ranges, thus verifying the hypothesis. The experiment has discovered generative subsidiary plants sprouting from the rhizomes of maternal ramets without entering the virginal stage. As a result, the LCG enriches with new reproductive pathways, and the new (not yet published) situations emerge where lambda1 fails in its accuracy as a measuring tool of comparative plant demography. We propose a general method to adjust the adaptation measure in this kind of situation. PMID- 26852571 TI - [Rate of microsuccessions: Structure and floristic richness recovery after sod transplantation in alpine plant communities]. AB - Reciprocal transplantations of sod pieces have been conducted in alpine plant communities of the northwestern Caucasus. During 25 years, the changes in floristic richness and successional rates have been registered. Study objects were chosen to be. plant communities located along the toposequence from ridges to hollows with gradient of snow. cover thickness increase and vegetation period decrease, namely alpine lichen heath (ALH), Festuca varia grasslands (FVG), Geranium-Hedysarum meadows (GHM), and snow bed communities (SBC). The results of the study confirm the hypothesis about floristic richness of transplanted pieces to come closer to that of a background acceptor community. It is shown that during succession the variability reduces if sod pieces from different communities are transplanted into a common one. In particular, this is evident in case of SBC, where floristic richness of sod pieces transplanted from ALH and GHM has reduced noticeably. Also, it is evident from the results that the more different are donor and acceptor communities the higher is the rate of their changing. However, the assumption of higher succession rate in more productive communities has not been affirmed. On the opposite, communities with initially low productivity turned out to change faster than those with high productivity. It is found out that sod pieces transplanted to upper areas of the toposequence have had higher rate of alteration in comparison with those transplanted to lower areas. The reason behind this, as it may be suggested, is a longer growth season, which means a more prolonged period of high functional activity, and, accordingly, more time for the effects of competition, bringing seeds over, etc. In whole, the rate of succession decreases as the time from the moment of transplantation.increases, especially in communities with low productivity. PMID- 26852572 TI - [Pathways and rates of Pinus sylvestris L. and Picea species recolonization into Scandinavia in Holocene]. AB - The results are presented of comparative analysis of pathways, rates, and timing of recolonization into Scandinavia, in Holocene, of Pinus sylvestris populations and those of Picea abies and P. obovata. The dispersion rate, starting from 12 thou years before present (BP), is calculated using palynological data from scientific literature on radiometric dating. It is found out that P sylvestris spread into Central Scandinavia from the Alps via the Danish Isthmus about 8.2 thou years BP with the speed of 500-1250 km per 1 thou years. A hypothesis is put forward suggesting that such a fast speed is due to pine seeds hydrochory, which is much faster than anemochory according to our researches. From the northern part of the East European Plain, P. sylvestris spread into Fennoscandia with lower speed (520 km per 1 thou years). Populations of Picea species dispersed from the same regions with speed (131-164 km per 1 thou years) 3-10 times lower than that of P. sylvestris. Therefore, invasion of Picea abies from the Alps into Scandinavia via the Danish Isthmus did not have time to happen before the formation of the Kattegat Strait. By circumferential pathway, through Karelia, both species of Picea reached the northern parts of Scandinavia only 3.5 thou years BP, its central parts - 2 thou years BP, and its southern parts - 1.5 thou years BP, i.e., later than P. sylvestris by 4, 6.2, and 8.5 thou years respectively. Probably, this may be explained by the fact that in pines the time to seeding is twofold shorter, while their sprouts were more tolerant to climatic extremums in periglacial habitats in middle Holocene. PMID- 26852573 TI - [Dolphin's flukes: A mathematical model of rigid wing]. AB - New analytical method is used to estimate hydrodynamic forces produced by dolphin's flukes. A mathematical model is proposed that describes dolphin's flukes as a flat rigid rectangular wing whose pitch axis location varies, heaving and pitching amplitudes are sufficiently large, and the phase angle shift for the combined oscillations can change arbitrarily. The dolphin's flukes kinematic parameters are obtained and used to estimate hydrodynamic forces. PMID- 26852574 TI - [PREDICTORS OF RISK OF SURGERIES IN PATIENTS WITH FAILURE OF THE CORONARY CIRCULATION]. AB - The paper analyzes the study of the myocardium in patients with coronary artery disease to identify new predictors of reduction of myocardial contractility. Research carried out on the basis of transthoracic echocardiography and transesophageal on Vivid 7 unit and Vivid-E9 with multifrequency array sensor (3.5-5.5 MHz) by method with the obligatory registration ofstandard ECG. All studies in the form of static and moving images (3-5 cardiocycles Cine-loop) is stored in workstation memory Echopac 7 (GE Vingmed Ultrasound, USA). To assess the functional state of left ventricular myocardium was measured geometry of the cavities of the heart and determines the main central hemodynamics: end-diastolic and end-systolic volume qf the left ventricle, the si:e of the left atrium, the rate of displacement of the myocardium ofivector analysis, stroke vohne, duration of the phases ofthe cardiac cycle, the pressure in the pulmonary circulation. In patients with low reserves, changes are observed during the period of contraction and relaxation. The maximum rate peaks do not coincide, and are significantly reduced compared with the outcome. Acceleration, velocity of bloodflow in the left ventricular cavity shows changing the direction of blood flow--this is nothing other than the power characteristic, which reflects energy during the contraction. Determination of the eddy currents and the velocity characterizes the acceleration of change in the direction of blood flow PMID- 26852575 TI - [ECHOCARDIOGRAPHIC PREDICTORS OF THE SEVERITY OF THE EARLY POSTOPERATIVE PERIOD IN PATIENTS AFTER SURGICAL MYOCARDIAL REVASCULARIZATION]. AB - Non-invasive and easily interpretable methods for assessing cardiac hemodynainic parameters including various echocardiographic technologies are highly valuable diagnostic methods in cardiac surgery patients admitting the intensive care unit in the postoperative period. The article presents echocardiographic features of the myocardial functional state in the early period after coronary artery bypass grafting performed in 201 CHD patients. The analysis includes standard echocardiographic parameters and data obtained from tissue Doppler imaging. Tissue Doppler imaging has shown to be informative for diagnosing heart failure. Low left ventricular volumes and restrictive type myocardial diastolic dysfunction have proven to be early echocardiographic predictors of poor prognosis in CAD patients after myocardial revascularization. PMID- 26852576 TI - [MODERN TECHNOLOGIES OF THE SAVING OF PATIENT'S BLOOD AND REDUCTION OF THE USE OF DONOR BLOOD DURING OPERATIONS ON THE ASCENDING AORTA AND AORTIC ARCH]. AB - Questions of saving of the patient's blood and limitation of the use of donated blood in the aortic surgery remain relevant in contrast with interventions on the valves of the heart and coronary arteries. In this regard, the aim of the study was to develop and introduce ofcomplex of technologies for saving the patient's blood in order to minimize transfusion of donor blood components during operations on the ascending aorta and aortic arch under hypothermic arrest. The study included 37 patients operated on the ascending aorta and aortic arch under cardiopulmonary bypass (CPB) and hypothermic cardiac arrest (CA) in 2013-2014 (Group 1). 2nd group consisted of 65 patients who at the same time performed reconstructive surgery on the ascending aorta with CBP without stopping the blood circulation. The comparative aspect studied the following parameters: duration of the CBP, CA, temperature, volume of intraoperative and postoperative blood loss, frequency of use of donor blood components autoplasma, washed red blood cells, autologous blood, hemostatic agents, the frequency resternotomy, hematocrit dynamics, glucose, and blood lactate. Comparative studies have shown that the amount of intraoperative blood loss during operations on the aortic arch under the CA was 1294 +/- 303 mL, 20% higher than the blood loss during operations on the ascending aorta without CA. Program of saving of the blood of patients with aortic disease included preoperative preparation of autoplasma in 60% of patients, intraoperative collection and laundering of autoerythrocytes in 40-70% of patients and autotransfusion modified method, the improvement of surgical and pharmacological hemostasis and monitoring. Design and implementation of these methods reduced the patients need for donor red blood cells (from 76 to 47%), fresh frozen plasma (from 65 to 35%) during the operation at the aortic arch and the ascending aorta and to completely avoid the use of donor blood in 25% of patients. Proof of the adequacy of the developed strategy of conservation and limitation of the patient's blood was allogeneic blood conservation targets hemoglobin, hematocrit levels and metabolism at the end of the operation. PMID- 26852577 TI - [ANAESTHETIC MANAGEMENT OF RECONSTRUCTIVE SURGERY ON THE AORTIC ARCH: THE NUANCES OF ORGAN PROTECTION]. AB - Aortic arch reconstruction is one of the most difficult surgical procedures. Therefore the aims of our study were: to choose appropriate flow rate for antegrade cerebral perfusion and assess its adequacy in relation to cerebral metabolic demands; to evaluate safety of temperature settings during the surgery; to assess the effectiveness of chosen protocol for brain and visceral organ protection during aortic arch reconstruction surgery. Our study included 67 patients. Patients of the first group (n = 33) underwent aortic arch reconstruction with antegrade cerebral perfusion and hypothermic circulatory arrest (target core temperature 26 degrees C). The second group (n = 34) underwent ascending aorta repair using cardiopulmonary bypass with modest hypothermia (target core temperature 32 degrees C). Cerebral and tissue oxygenation monitoring was performed in all patients. In the first group transcranial Doppler monitoring and jugular venous bulb catheterization were performed. Target core temperature during rewarming was 36 degrees C. In the first group air-warming device in addition to fluid warming was used. In all patients cognitive function was assessed before and after surgery. The multimodal monitoring allowed to dynamically adjust flow rate of antegrade cerebral perfusion. As a result cerebral SO2 and linear velocity were maintained in acceptable range, while flow rate varied significantly from 5.8 to 16.5 ml/ kg/min (average rate 13.4 +/- 3.69 ml/kg/min). CONCLUSION: Combined use of cerebral oximetry and transcranial Doppler monitoring allows assessing how oxygen delivery meets metabolic demands of the brain during antegrade cerebral perfusion. This method allows to maintain the proper flow rate of antegrade cerebral perfusion and to choose an appropriate modification of perfusion (unilateral vs bilateral). Multichannel monitoring of core temperature and combined use of air- and fluid warming techniques are required for effective temperature management. PMID- 26852578 TI - [ACUTE KIDNEY INJURY IN PATIENTS WITH MULTIPLE ORGAN DYSFUNCTION SYNDROME IN THE EARLY PERIOD AFTER CARDIAC SURGERY]. AB - Acute kidney injury can greatly increase the severity of multiple organ dysfunction syndrome (MODS) and impair patient outcomes. OBJECTIVE: To study the clinical significance of acute kidney injury in patients with MODS in early postoperative period after cardiac surgety and its influence, on the severity of the patient condition and outcomes. MATERIALS AND METHODS: The study involved 117 patients aged 57.2 +/- 1.2 years. The Group 1, control, included 74 patients with uncomplicated postoperative period; the Group 2--43 patients with MODS, who were divided into the survivors (33 patients, group 2a) and deaths (10 patients, group 2b). RESULTS: In Group 2. thefollowingparaineters were higher--the volume of blood loss by 1.5 times (p = 0,001), the duration of the cardiopulmonary bypass 1.7 times (p 0.001), and aortic clamping 1.6 times (p = 0,001). Group 2a and 2b on these indicators did not differ Average scale Group 2b was 1,3-fold higher than in survivors (p = 0,001). Patients differ in the severity of the central nervous system disorders (the average score of Glasgow Coma Scale survivors was 1.3 times higher P = 0,001) and severity of acute kidney injury On a RIFLE scale patients of group 2a normal data was observed in 12%, the stage of risk in 61%, and damage in 27%. In 50% of the dead was a stage of disease (p = 0.04), the rest -damage. In the dynamics of the group 2b impaired renal and hepatic functions have progressed. By day 3 ASTwas on average 2-fold higher (p = 0.01), ALT (1.9 fold, p = 0,001), alkaline phosphatase 1.5 times (p = 0.001), while the total blood protein below 1.3 times (p = 0.00 1), than in group 2a. Creatinine in patients of Group 2b was 1.4 tunes higher (p = 0,036), urea 1.6 (p = 0.026), u NGAL 7 times higher (p = 0.001), than in group 2a. CONCLUSIONS: Long cardiopulmonary bypass, clamping of the aorta and a large amount of perioperative the risk of MODS in the early postoperative period, but do not affect the outcome. On the background of the dzvelopment of MODS an average score on MODS-2 scale died was 1.3 times higher in Group 2b than in survivors. Marked renal dysfunction in cardiac surgical patients with MODS is a sign of poor prognosis. With the development of MODS, a renal dysfunction ahead worsens hepatic function. The value qf the marker u-NGAL is the strongest indicator of the severity of acute kidney injury and poor outcome of treatment in these patients. PMID- 26852579 TI - [CORRECTION OF HEMOSTASIS WITH BLOOD PRODUCTS IN THE SURGICAL TREATMENT OF CONGENITAL HEART DISEASE IN INFANTS AND YOUNG CHILDREN]. AB - The article deals with the safety and efficiency of recombinant activated factor VII (Coagil VII, Russia) and prothrombin complex concentrate (protromplex-600, Baxter Austria) in the neonatal and pediatric cardiac surgery. The study included 56 children aged from 7 days to 5.5 years underwent surgery with cardiopulmonary bypass for congenital heart defects repair. Clinical and laboratory evidences suggest that Coagil VII and protromplex-600 effective for bleeding stop. The drugs have no negative impact on hemodynamics. We did not identify allergic reactions and thrombosis associated with the introduction of drugs in the pen operative period. PMID- 26852580 TI - [THE EFFICACY AND SAFETY OF DEXMEDETOMIDINE FOR SEDATION OF PATIENTS DURING PROLONGED MECHANICAL VENTILATION IN INTENSIVE CARE UNITS (RUSSIAN MULTICENTER STUDY RESULTS)]. AB - A multicenter prospective study investigated the efficacy and safety dexmedetomidine of sedation in 103 patients during long-term (> 12 h) mechanical ventilation and in cases of delirium. Protocol of sedation included intravenous infusions of dexmedetomidine 1.4/kg/h and administering of analgesic drugs, and if necessary--sedative drugs (propofol, midazolam). Group 1 included 69 patients in whom dexmedetomidine sedation was performed for prolonged mechanical ventilation. Group 2 consisted of 34 patients in whom dexmedetomidine was used due to development of delirious state. Dexmedetomi- dine was used as an infusion of 0.7 mg/kg for 1 hour with further correction of dosage. We recorded a level of sedation by RASS, the need for the appointment of other drugs with sedative effects, the duration of mechanical ventilation, length of ICU stay. The infusion of dexmedetomidine can provide a target level of sedation for RASS from 0 to -3 at 80-90% of patients with surgical and therapeutic profile who underwent prolonged mechanical ventilation. The frequency of adverse events appeared due to the development of bradycardia, hypotension. In the use of dexmedetomidine bolus injection should be avoided. PMID- 26852581 TI - [STROKE: INCIDENCE AND RISK FACTORS FOR VENOUS THROMBOEMBOLIC COMPLICATIONS IN INTENSIVE CARE UNIT]. AB - AIM: To study the evidence of venous thromboembolic complications (VTE (acute venous thrombosis (DVT) and pulmonary embolism (PE)) at the background of modern prevention for different characteristics and localization of stroke, as well as defining the role of the main clinical risk factors in the pathogenesis for ITE in stroke patients in intensive care unit. MATERIAL AND METHODS: The study included 123 patients with different types, localization and severity of stroke. All patients received standard prophylaxis VTE with low molecular weight heparin (LMWH). Neurological status, the severity of the general condition, the main clinical risk factors of stroke were assessed when income and in dynamics. There was planned duplex scanning of the veins of the inferior vena cava performed. RESULTS AND DISCUSSION: In spite of the application of modern preventive measures VTE, their frequency remains high accounting for 56%. All patients have a place DVT, in 26% of pulmonary embolism occurs. Groups at highest risk of VTE are patients with stroke more than 8 points of NIHSS, who are ventilated and assessed infection-inflammatory disorders, especially pulmonary. This group is considered to be at the highest risk of VTE. Modern preventive strategy for them is not sufficient and needs for the search of other preventive approaches. PMID- 26852582 TI - USE OF MESENCHYMAL STROMAL STEM CELLS FOR THE TREATMENT OF SEPSIS. AB - The article deals with description of multipotent mesenchymal stromal cells (MMSCs), the mechanisms, the effects and uses of MMSCs for the treatment of sepsis and septic shock, and overview of the experimental data on the use of MMSCs in sepsis obtained in studies in cell cultures and in different models of sepsis in animals. PMID- 26852583 TI - [INFLUENCE OF EXTRACORPOREAL DETOXIFICATION METHODS ON TISSUE PERFUSION IN SEPTIC SHOCK]. AB - OBJECTIVE: To improve the results of abdominal sepsis treatment by comprehensive application of extracorporeal detoxification methods controlled by tissue perfusion. SUBJECT AND METHODS: Fifteen patients with abdominal sepsis were examined, septic shock was diagnosed to all of them. Patients were divided into two groups. The first group (n = 7) consists of patients with acute renal failure, who had undergone adsorption of Lipopolysaccharide. The second group (n = 8) consists of patients with acute renalfailure, who had undergone prolonged hemofiltration regardless of the products of nitrogen metabolism level to terminate systemic inflammatory response. Dynamic monitoring of tissue perfusion was performed using Doppler ultrasound flowmeter methods. RESULTS: According to high frequency Doppler ultrasound results all the patients with abdominal sepsis have significant peripheral circulatory disorders maintaining in volumetric and linear blood flow velocity reduction. As a result of application extracorporeal detoxification methods indexes of tissue perfusion were improved. Performance of selective endotoxine hemosorbtion and hemofiltration provides substantially stabilizing effect on Doppler microcirculation indexes: average volumetric blood flow velocity (Qam) increased 4.5 times, end-diastolic linear blood flow velocity (Vakd)--increased to 85%, peripheral resistance index (RI) reduced 2.8 times. Doppler tissue perfusion indexes monitoring allows directly monitor extracorporeal detoxification methods effectiveness, supplementing system hemodynamic monitoring data. CONCLUSION: Timely application extracorporeal detoxification methods in abdominal sepsis can improve tissue perfusion. PMID- 26852584 TI - [EXTRACORPOREAL BLOOD CORRECTION METHODS AND THEIR IMPACT ON PRODUCTS OF MICROBIAL METABOLISM IN PATIENTS WITH SEPSIS]. AB - Sepsis is a disease with a high death-rate and is accompanied by profound metabolic disturbances. Interference of microbe metabolic products with biochemical processes in human organism is present in case of severe infection. But there is little information about integration of microbe and human metabolism in septic patients. We evaluated an indol level in healthy individuals and septic patients. It was revealed that septic patients have higher indol levels. Hemoperfusion through "Ovosorb" sorbing agent allows to decrease indol concentration to normal levels. Application of hemosorbtion in combination with magnetic blood processing allows achieving faster and more effective indol removal. PMID- 26852585 TI - [EXPRESS IDENTIFICATION OF POSITIVE BLOOD CULTURES USING DIRECT MALDI-TOF MASS SPECTROMETRY]. AB - OBJECTIVE: To evaluate the effectiveness of direct identification of pathogens of bacteremia by direct matrix assisted laser desorption ionization time-flight mass spectrometry (mALDI-TOF) compared to routine method. MATERIAL AND METHODS: A prospective study included 211 positive blood cultures obtained from 116 patients (106 adults and 10 children, aged from 2 weeks to 77 years old in the ICU after open heart surgery. Incubation was carried out under aerobic vials with a sorbent for antibiotics Analyzer BacT/ALERT 3D 120 (bioMerieux, France) in parallel with the primary sieving blood cultures on solid nutrient media with subsequent identification of pure cultures using MALDI-TOF mass spectrometry analyzer Vitek MS, bioMerieux, France routine method), after appropriate sample preparation we carried out a direct (without screening) MALDI-TOF mass spectrometric study of monocomponental blood cultures (n = 201). RESULTS: using a routine method in 211 positive blood cultures we identified 23 types of microorganisms (Staphylococcus (n = 87), Enterobacteria- ceae (n = 71), Enterococci (n = 20), non-fermentative Gram-negative bacteria (n = 18), others (n = 5). The average time of incubation of samples to obtain a signal of a blood culture growth was 16.2 +/- 7.4 h (from 3.75 to 51 hours.) During the first 12 hours of incubation, growth was obtained in 32.4% of the samples, and on the first day in 92.2%. In the direct mass spectrometric analysis mnonocomponental blood cultures (n = 201) is well defined up to 153 species of the sample (76.1%), while the share of successful identification of Gram-negative bacteria was higher than that of Gram-positive (85.4 and 69, 1%, respectively p = 0.01). The high degree of consistency in the results of standard and direct method of identifying blood cultures using MALDI TOF mass spectrometry (kappa = 0.96, p < 0.001; the samples included in the calculation for which both option given result). Duration of the direct mass spectrometric analysis, including sample preparation, was no longer than 1 hour: CONCLUSION: The method of direct MALDI-TOF mass spectrometry allows to significantly speed up the identification of blood cultures that may contribute as much as possible early appointment effective regimes of starting antibiotic therapy. PMID- 26852586 TI - [LEVOSIMENDAN--THE FIRST 10 YEARS IN CLINICAL PRACTICE]. AB - The article deals with a survey of the main pharmacological effects of levosimendane. Special attention is paid to cardiac and organ protective properties of the medication. The article reviews literature data on the efficacy of levosimendan in various fields of medicine and in the experiment and highlights the problem of heart failure and low cardiac output syndrome treatment in cardiology and cardiac surgery. PMID- 26852588 TI - [Review of existing scales of assessment of severity in neonates with critical congenital heart disease]. PMID- 26852587 TI - [POSSIBILITIES OF PHARMACOLOGICAL NEUROPROTECTION IN CARDIAC PATIENTS DRUGS NOT INTENDED FOR GENERAL ANESTHESIA]. AB - The following paper is the second part of pubished review which reveals today state of pharmacology in neuroprotection issue. In the first part of the review we discussed neuroprotective possibilities of anesthesia medicine, but there is also another trend in pharmacological neuroprotection which is on high demand today: medicine that are not general anaesthesia drugs. This paper surveys medicines from different pharmacological groups and possible neuroprotective properties of these medicine are widely discussed in medical media. Unlike anesthetic medicine, most drugs mentioned in the second part of the review, can be used both for primary and secondary neuroprotection. The survey presents data from experimental and clinical studies of medicines neuroprotective properties. PMID- 26852589 TI - [On the 85th anniversary of RAS Academician, Professor Armen Bunyatyan]. PMID- 26852590 TI - [Fatty acid composition in the carotid artery tissue in the atheromatosis and lipid spot areas. Universal pathogenesis of the atherosclerosis syndrome and its symptom of intimal atheromatosis]. AB - Gas chromatography with mass spectroscopy detection have shown that the major components of atheromatous masses in formed atherosclerotic plaques (surgery material) are the derivatives of essential polyenic fatty acids (ES poly-FA) and of the alcohol cholesterol. They undergo nonphysiological catabolism (hydrolysis) in the lysosomes of resident macrophages as components of protein macromolecules, low-density lipoproteins (LDL). In excess of palmitic triglycer- ides apoB-100 of LDL does not form ligand, and ligand-free LDL become biological in the circulation. They are uptaken via scavenger receptors by resident macrophages in the intima. When ligand LDL are physiologically uptaken via apoB-receptors, they are catabolized (oxidized) in peroxisomes but not in lysosomes. Lipid spots result from functional cellular lipoidosis which fulfills the biological reaction of inflammation and initiate the lipoidosis--vector protein for FA transport--C reactive protein pathway. Formation of ligand-free LDL lays the basis for intracellular ES poly-FA deficiency and clinical manifestations of the atherosclerosis syndrome. Intima is the spot where large-molecular-weight (> 70 kD) biological rubbish is collected and utilized from a local intravascular pool of the intercellular medium. PMID- 26852591 TI - [Serum markers of fibrosis and endothelial dysfunction in patients with alcoholism, with varying degrees of liver fibrosis]. AB - In the serum of patients with alcoholism with varying degrees of severity of liver fibrosis were studied the content markers of fibrosis, endothelial dysfunction and proinflammatory cytokines. Concentration in blood indicators of fibrogenesis--collagen type 4, hyaluronic acid, TIMP-1, TIMP-2, YKL-40 and MMP-2 is considerably increased at the 4 degree of fibrosis and moderately increased at low and zero degrees of liver fibrosis. Similar results were obtained in respect of proinflammatory cytokines Il-6, IL-8, IL-12/p70 and IL-12/p40. The magnitude of endothelial dysfunc- tion, calculated based on its content in the blood markers--VEGF-A, MCP-1, s-VCAM, s-ICAM and endothelin, was maximal at 4 degrees of fibrosis and less pronounced at low degrees of fibrosis. Correlations between of the average degree of fibrosis, endothelial dysfunction, and blood levels of proinflammatory cytokines were installed. Close relation between the immune cells releasing stimulators of inflammation and fibrogenesis, perisinusoidal fat cells producing collagen, and endothelium secreting vasoconstrictors in the pathogenesis of alcoholic liver fibrosis and cirrhosis was installed. PMID- 26852592 TI - [Comparison of neuroprotective effects of derivatives of eritropoetine by different way of bringing in drugs with model of bilateral photochemically induced thrombosis of the prefrontal cortex of rat brain]. AB - It was stated with model of bilateral photochemically induced thrombosis of the prefrontal cortex by injected intranasally or intraperitoneally in 1h after operation new derivatives of eritropoetine: Epo, Epo-Fc, Epo-Tr provoked neuroprotective and antiamnestic action. Epo-Fc demonstrated more effective action by intranasal injection. PMID- 26852593 TI - [Hypercapnia--alternative hypoxia signal incentives to increase HIF-1alpha and erythropoietin in the brain]. AB - Investigated the role of hypercapnic component in the mechanism of activation of HIF-1alpha and increase the synthesis of erythropoietin in the combined and the isolated impact of hypoxia and hypercapnia. It was found that the content of proteins of interest significantly increases both in isolated hypoxia and hypercapnia, and at their combined effect. Moreover, the hypercapnic hypoxia causes maximum activation of the synthesis and accumulation of erythropoietin HIF 1alpha, and permissive hypercapnia enhances their content more than hypoxic exposure. PMID- 26852595 TI - [Relationship between sex hormones, pheromones, interleukine production and risk of drug dependence]. AB - Serum steroid hormones and production of proinflammatory cytokines in 109 individuals with substance dependence, 34 occasional users and 78 control subjects were examined. Immaturity of gender as a risk factor for the formation of drug dependence associated with infectious and inflammatory processes was estimated by olfactory pheromone tests. PMID- 26852594 TI - [Autoantibodies to glutamate and GABA in opiate addiction]. AB - Blood serum from 129 patients with opium addiction at different stages of the disease and 63 donors (control group) was examined for the presence of autoantibodies to the exciting and inhibitory amino acids glutamate and GABA. It was shown enhanced production of autoantibodies to glutamate and GABA. Dependence of the level and frequency of detec- tion of autoantibodies to glutamate and GABA on the stage of the disease was revealed. PMID- 26852596 TI - [Monitoring of human physiological functions during the daily night sleep]. AB - The basic somnological methodology, which is extensively used in the present time, focuses only on clinical practice. However, this approach is not appropriate for monitoring of physiological functions during natural sleep under home conditions. Our work was designed to develop a new information-and-equipment device for the reliable study of human physiological functions during sleep in the real everyday life. The information complex is a new portable microprocessor device and original software, which is constructed on the basis of PC and provides a control of vital physiological functions during sleep in the real everyday life. We developed a new methodology for the objective comprehensive study of sleep under real day-to-day conditions. This approach allows us to identify the phase structure of sleep and to control cardiovascular functions and breathing on the basis of a cross-correlation analysis of the heart rate and respiratory rate (that reflects the degree of emotional strain). The information system for control of sleep under living conditions is composed from interrelated units, which perform the following functions: registration, identification, and analysis of the phase structure of sleep; wake-up of a subject in a certain time during the pre-determined optimal phase of sleep (as regards the psychophysiological state of this subject); and interruption of a long-lasting hazardous phase of sleep. Due to a complex analysis of physiological functions, the information system provides monitoring of sleep under real living conditions and interruption of hazardous phases of sleep that can be accompanied by serious cardiovascular disorders (i.e., leading to cerebral stroke, myocardial infarction, and sudden death). PMID- 26852597 TI - [Changes of endotoxin concentration in blood serum in patients with uncomplicated acute myocardial Q-infarction]. AB - The effectiveness of acute myocardial infarction (AMI) treatment does not correspond to high material costs for the study of its pathogenesis and development of new drugs. This circumstance gives the grounds to assume existence of nowadays unknown mechanisms of emergence and development of this disease. High probability of participation of endotoxin (ET) in the pathogenesis of AMI was theoretically proved by us for more than a quarter of the century ago, but it's clinical evidence to date is not found yet. As a result of the study a significant increase of endotoxin (ET) concentration in the blood serum of patients with AMI increasing from 1 to 14 day of the disease has been found. In women the concentration of ET was higher than in men. It allows to qualify the EA as a factor probably influencing the known difference in AMI tolerance in men and women. The source of ET were Bacteroides (most often--67.8% of patients), Klebsiella, Pseudomonas, Proteus, Escherichia coli. One or two bacteria more often took part in the development of EA. In 9.1% of patients the etiology of EA could not be verified, what indicates the presence of other sources of EA, not evaluated in this study. In 25% of patients with AMI serologic evidence of systemic candidiasis, caused by candida Albicans, has been found, what is able to enhance the biological effects of ET. PMID- 26852598 TI - [The influence of erythrocyte-derived microvesicles on aggregation of platelets in burn injury]. AB - Burn Injury is accompanied by a significant homeostasis disorder, including the disorder of primary homeostasis, associated with aggregation of platelets. The role of erythrocyte-derived microvesicles in this process has not undergone thorough research. Microvesicles were isolated from washed erythrocytes after one day of storage by ultracentrifugation at 100000 g. The number of MVs was determined by flow cytometry and was standardized in the samples. Heparin dependent and heparin-independent antithrombin activity in erythrocyte microvesicles was studied by coagulation method. We studied platelet aggregation induced and not induced by ADP under the conditions of artificial shear flow. It was shown that at the early stage of bum injury the number of erythrocyte-derived microvesicles in blood demonstrated a 4.2-fold ncrease. We determined that microvesicles, derived from the erythrocytes of burn patients displayed a significantly less aggregation activity than the microvesicles from donors. The main reason is a considerably lower antithrombin activity in the erythrocyte microvesicles of bum patients. Thus, we can conclude that the decrease of antiaggregation and antithrombin activity of erythrocyte microvesicles associated with the increase in their concentration in blood contributes to thrombophilia of bum patients. Keywords: erythrocytes, microvesicles, bum injury, platelet aggregation, antithrombin activity PMID- 26852599 TI - [Effects of lithium carbonate nanosized particles on nitric oxide production and arginase activity in tumor and peritoneal macrophages in hepatocellular carcinoma 29]. AB - Three groups of male CBA mice were used. Group 1 consisted of intact mice. Hepatocarcinoma cells 29 (HCC-29) were transplanted into the right thigh muscle of animals group 2. Group 3 mice were injected 0.1 ml of lithium carbonate nanosized particles (NPs Li2CO3) at a dose of 0,058 mg on periphery of tumor growth one fold (3 day) and 5-fold (7 and 13 days). On day 7, numerical density of macrophages was raised in 5.8 times, the NO levels were increased by 1.9 times, and arginase activity was decreased in HCC tissue as compared with those values in normal liver. Tumor growth led to an increase in NO production by peritoneal macrophages (pMf) in 2.8 and 2.2-fold on day 7 and 13 days, respectively, and hadn't effect on arginase activity. A single injection of NPs Li2CO3 after inoculation tumor cells (3 days) didn't alter the NO levels rise in the tumor but five injections (7 days) increased it in 1.7 times as compared with values of mice group 2. The treatment of NPs Li2CO3 influenced the increasing the number density of macrophages in the tumor. Numerical density of macrophages in the tumor of mice group 3 was increased 9.6 and 1.6 times as compared with similar values in groups 1 and 2, respectively on 7 day after 5 injections of NPs Li2CO3. Treatment of NPs Li2CO3 after tumor cell transplantation didn't affect on the rise of NO levels and arginase activity in pMf. Thus, the effects of NPs Li2CO3, administered after HCC-29 cells transplantation, aimed at increasing activity of the NO-synthase way in HCC tumors and pMf, which can reduce the arginine levels required for tumor growth. PMID- 26852600 TI - [The comparative characteristic of level of histamine, IgE and IgG in blood and the lymph at the experimental anaphylactic shock and Artyus phenomenon]. AB - Maintenance changes of histamine and levels of immunoglobulin E and G in blood and lymph are studied at the ex- perimental anaphylactic and Artyus phenomenon. Experiments were conducted in two series on 27 rabbits of "Chinchilla" breed. As control are served the investigated indicators of concentration of histamine and levels of IgE and IgG in blood and lymph of intact animals. Results of research have shown that, at the experimental anaphylactic shock increase the level of IgE and decrease the level of IgG. At the Artyus phenomenon increase of level of IgG and the decrease in level of IgE more expressed in blood, than in lymph is marked. Concentration of histamine raises, both at the anaphylactic shock, and at the of Artyus phenomenon, but is more expressed at anaphylaxis, and also in blood, than in lymph. Key words: anaphylactic shock; Artyus phenomenon; histamine; immunoglobulin PMID- 26852601 TI - [Inflammatory and autoimmune reactions in different forms of nervous system functioning disorders]. AB - Parameters of innate (the leukocyte elastase (LE) and alpha1-proteinase inhibitor (alpha-1-PI) activity) and adaptive immunity (the level of autoantibodies to neuroantigens nerve growth factor (NGF) and myelin basic protein (MPB)) were studied over time in the blood serum of 107 children with perinatal hypoxic ischemic encephalopathy; 188 children with autism spectrum disorder; 108 patients with schizophrenia. The correlations between immunological parameters and clinical status assessment in all groups of patients using psychometric scales were analyzed. The involvement of innate immunity, i.e. inflammatory reactions, in pathogenesis of all analyzed forms of nervous system functioning disorders was confirmed. The activation of adaptive immunity, i.e. autoimmune reactions, was found only in the group of patients with the most severe forms of nervous system functioning endogenous disorders. The results indicate that the inflammatory and autoimmune reactions are pathogenic mechanism of all studied forms of nervous system functioning disorders. PMID- 26852602 TI - [The role of cellular mediators in the development of the phenomenon of inhibition induced by barium sulfate luminol-dependent chemiluminescence of blood under the influence of non-steroidal anti-inflammatory drugs in patients with intolerance to these drugs]. AB - We investigated contribution mediator mechanism in the development of the phenomenon of inhibition induced by barium sulfate luminol-dependent chemiluminescence (SLCHL) of blood under the influence of nonsteroidal anti inflammatory drugs (NSAIDs) in patients with intolerance to these drugs. It was found that the phenomenon of suppression SLCHL blood under the influence of NSAIDs in patients with intolerance is mediated by the participation of mediators, and the contribution of H1--and H2--histamine receptors, 5-HT2 serotonin receptors and Cys-leukotriene receptors in the development of that phenomenon depends on the chemical nature of NSAIDs and the clinical manifestations of intolerance. PMID- 26852603 TI - [The effect of low frequency electrical stimulation on bone tissue regeneration]. AB - The study was performed on 30 male rats of Wistar line (weight 330-360 g, age 3.5 months).In an experimental model of damage to the femur bone in the hip joint studied the effect of low frequency electrical stimulation of the damaged area on the rate of regeneration of bone. The animals were divided into two groups. Control (15 rats) and experienced (15 rats). In the experimental animals underwent stimulation of the injury site for 5 min daily for 7 days, 14 days and 21 days. Stimulation was carried out using a device "Osteon-1" generating a mixed signal of two voltage pulse of varying duty cycle, one of which is modulated to a higher frequency. Signals were not synchronized with respect to each other, unipolar with varying frequencies and amplitudes. The obtained results show the effectiveness of the electrical stimulation currents of low frequency in the restoration of bone tissue after damage. Morphological studies showed that electrical stimulation to accelerate the regeneration of damaged bone at all stages of the study (7, 14, 21 day), causes a more pronounced integration of newly formed bone with the old intact bone and promote the formation of more powerful periosteal calluses in comparison with the control. PMID- 26852605 TI - [Prospects for the Use of Cells Possessing Myogenic Potential in the Treatment of Skeletal Muscle Diseases: a Review of Research. Part 2--Populations of stem cells of muscle and non-muscle origin]. AB - The paper reviews research results of myogenic potential, specific properties, functions, and phenotypic features of a number of stem cells populations of muscle and non-muscle origin, their ability to participate in the restoration of the physiological homeostasis of skeletal muscle. The results of scientific research allow to predict with high probability the establishment of an effective cell technology to treat degenerative muscle diseases. PMID- 26852604 TI - [Ability of human monocytes to activate in atherosclerosis]. AB - Monocytes were isolated from blood of patients belonging to three groups: those with normal intima-media thickness (IMT) of carotid arteries, patients with increased IMT and patients with atherosclerotic plaques. The degree of activation of the macrophages was determined by the concentration of the cytokine TNF-alpha and chemokine CCL18 in the culture medium. When comparing the average values of the concentrations of TNF-alpha and CCL18 for patients in all groups dramatic individual differences were revealed. These individual differences were found within each group and in the pool. An inverse relationship between intracellular cholesterol levels and the ability of monocytes to activate was found. To clarify the cause of this relationship, monocytes were cultured with atherogenic modified low-density lipoprotein, causing accumulation of cholesterol in cultured cells. The accumulation of intracellular cholesterol had no effect neither on the secretion of cytokines nor on the expression of their genes. Therefore, individual differences in the activation capacity of monocytes is not determined by the accumulation of intracellular cholesterol caused by atherogenic lipoproteins. The data obtained can be explained by the individual characteristics of the immune response in different patients. PMID- 26852606 TI - [Epigenetic, post-transcriptional and metabolic mechanisms of macrophage reprogramming]. AB - A key role in the ability of immunity to adequately respond to pathogenic factors play macrophages. Depending on the type of infection and the microenvironment macrophages can rapidly change their phenotype towards the proinflammatory M1 or antiinflammatory M2 one. The process of changing the cell phenotype is termed "reprogramming". This process plays a central role in the immune response and therefore its disturbance triggers the development of disease. Reprogramming of macrophages is provided by intracellular signaling pathways. These paths can also control epigenetic, post-transcriptional and metabolic mechanisms of phenotypic activity of macrophages. Epigenetic mechanisms can be divided into the reprogramming mechanisms towards M1 and M2 phenotype. A key component of post transcriptional regulation is micro-mRNA (miR). On M1- and M2-stimuli macrophages express different sets of miRs. MiRs may form a positive feedback mechanism for quick reprogramming of macrophages and negative feedback mechanisms, to limit excessive inflammation in the case of M1 phenotype and to restrict fall bactericidal activity in the case of M2 phenotype. Reprogramming of macrophages leads to a change in the metabolism of these cells. Formation of M1 phenotype accompanied by a shift of the arginine metabolism towards NO-synthase activation and increased production of NO, an increase in the contribution of glycolysis to ATP production, increased deposition of bacteriostatic iron. Formation of the M2 phenotype is accompanied by a shift of the arginine metabolism towards arginase 1 activation and increasing production of urea, increased ATP synthesis in mitochondria and increased capture of fatty acids, increased the capture of heme iron. Metabolic control of macrophage phenotype also involves the positive and negative feedback. In general, macrophage reprogramming involves very good coordinated and adapted to each other changes in the activity of signaling, epigenetic, post-translational and metabolic mechanisms. A detailed understanding of the mechanisms of reprogramming will assist in selecting the correct effective therapeutic targets to develop new ways for correction of impaired immunity. Keywords: immunity; macrophages; reprogramming PMID- 26852607 TI - [Macrophage activation in atherosclerosis. Message 1: Activation of macrophages normally and in atherosclerotic lesions]. AB - Macrophages play important role in initiation and progression of inflammation in atherosclerosis. Plaque macrophages were shown to exhibit a phenotypic range that is intermediate between two extremes, M1 (proinflammatory) and M2 (anti inflammatory). Indeed, in atherosclerosis, macrophages demonstrate phenotypic plasticity to rapidly adjust to changing microenvironmental conditions. In plaque macrophages demonstrate different phenotypes, and besides macrophage phenotypes could be changed. Phenotypes M1, M2, M4, Mhem, HA-mac, M(Hb) u Mox are described in the article. Ability of macrophages change their phenotype also considered. PMID- 26852608 TI - [Glutamatergic neurotransmitter system in regulation of the gastrointestinal tract motor activity]. AB - The review include actual facts, demonstrating high probability of glutamatergic neurotransmitter system role in the regulation of the gastrointestinal tract motor activity. These facts suggest significant role of the glutamatergic neurotransmitter system dysfunction in forming motor activity disorders of the digestive tract, including in patients in critical condition. The analysis is based on results of multiple experimental and clinical researches of glutamic acid and other components of the glutamatergic neurotransmitter system in central nervous system and autonomic nervous system (with the accent on the enteral nervous system) in normal conditions and with functioning changes of the glutamatergic neurotransmitter system in case of inflammation, hupoxia, stress and in critical condition. PMID- 26852609 TI - [To the 130th anniversary since the birth of the prominent pathologist N.N. Anichkov, academician of USSR Academy of sciences and Academy of medical sciences]. AB - The paper represents the research achievements and a course of life of the outstanding Russian pathologist, founder of the doctrine on atherosclerosis academician Nikolai Nikolayevich Anichkov. PMID- 26852610 TI - Transitioning from the Bench to the Classroom, an Education-Intensive Career. PMID- 26852611 TI - Caveat Emptor. PMID- 26852612 TI - Novo Nordisk Foundation Continues Support of APS Awards. PMID- 26852613 TI - Nebraska Physiological Society 18th Annual Meeting. PMID- 26852614 TI - APS Promotes Physiology to K-12 Teachers at Fall Meetings. PMID- 26852615 TI - 2015 APS/ET-14: International Conference on Endothelin: Physiology, Pathophysiology, and Therapeutics. PMID- 26852616 TI - Cardiovascular, Renal and Metabolic Diseases: Physiology and Gender. PMID- 26852617 TI - Letter to Lois Heller. PMID- 26852618 TI - Letter to Lois Heller. PMID- 26852619 TI - Screening of minor bioactive compounds from herbal medicines by in silico docking and the trace peak exposure methods. AB - Screening of high potent enzyme inhibitors from herbal medicines is always lacking of efficiency due to the complexity of chemicals. The constituents responsible for the holistic effect may be trace-level chemicals, but these chemicals were covered by highly abundant compositions. To challenge this bottleneck, a strategy for screening minor bioactive compounds was proposed. It generally included four steps, (1) preliminarily find the enzyme binders by ultrafiltration; (2) optimise and predict the potential inhibitors by docking analysis; (3) selectively identify and prepare trace compounds by segment and exposure approach; (4) validate the activity and summarize the structure-activity relationship. As a case study, alpha-glucosidase (AGH) and Ginkgo biloba extract were used as the experimental materials. By comprehensive screening, 11 trace flavones were screened out and identified as strong AGH inhibitors. Among them, AGH inhibitory activities of syringetin and sciadopitysin were reported for the first time. Their IC50 values were 36.80 and 8.29MUM, respectively, which were lower than that of a positive control acarbose. In addition, the AGH inhibitory activities of the flavonoids could be ranked, based on a decreased order, as biflavone, flavone, flavone glycoside, flavone biglycoside. The strategy is expected to be practical and useful for screening bioactive molecules from herbal medicines, especially for the minor compounds, which will definitely accelerate the discovery of new drug candidates. PMID- 26852620 TI - Highly selective and effective solid phase microextraction of benzoic acid esters using ionic liquid functionalized multiwalled carbon nanotubes-doped polyaniline coating. AB - The present work reports the electrochemical fabrication of an ionic liquid functionalized multiwalled carbon nanotubes-polyaniline (MWCNT@IL/PANI) nanocomposite coating and its application in the headspace-solid phase microextraction (HS-SPME) and gas chromatography (GC) determination of benzoic acid esters (i.e., methyl benzoate, ethyl benzoate, propyl benzoate and butyl benzoate). The MWCNTs was firstly functionalized with amine-terminated IL (MWCNT@IL) through chemical reduction, and then was doped in PANI during the electropolymerization of aniline. The resulting coating was characterized by infrared spectroscopy, field emission scanning electron microscopy and thermo gravimetry. It showed net-like structure and had high thermal stability (up to 330 degrees C). Furthermore, it presented high selectivity for the four benzoic acid esters and thus suited for their HS-SPME-GC determination. Results showed that under optimized extraction conditions, the detection limits were less than 6.1ngL(-1) (S/N=3) and the linear detection ranges were 0.012-50MUgL(-1) (R>=0.9957) for these analytes. The relative standard deviations (RSDs) were lower than 6.4% for five successive measurements with one fiber, and the RSDs for fiber-to-fiber were 4.4-9.6% (n=5). The developed method was successfully applied to the determination of these benzoic acid esters in perfume samples. PMID- 26852621 TI - A magnetic-based dispersive micro-solid-phase extraction method using the metal organic framework HKUST-1 and ultra-high-performance liquid chromatography with fluorescence detection for determining polycyclic aromatic hydrocarbons in waters and fruit tea infusions. AB - A hybrid material composed by the metal-organic framework (MOF) HKUST-1 and Fe3O4 magnetic nanoparticles (MNPs) has been synthetized in a quite simple manner, characterized, and used in a magnetic-assisted dispersive micro-solid-phase extraction (M-d-MUSPE) method in combination with ultra-high-performance liquid chromatography (UHPLC) and fluorescence detection (FD). The application was devoted to the determination of 8 heavy polycyclic aromatic hydrocarbons (PAHs) in different aqueous samples, specifically tap water, wastewaters, and fruit tea infusion samples. The overall M-d-MUSPE-UHPLC-FD method was optimized and validated. The method is characterized by: its simplicity in both the preparation of the hybrid material (simple mixing) and the magnetic-assisted approach (~10min extraction time), the use of low sorbent amounts (20mg of HKUST-1 and 5mg of Fe3O4 MNPs), and the low organic solvent consumption in the overall M-d-MUSPE UHPLC-FD method (1.5mL of acetonitrile in the M-d-MUSPE method and 2.8mL of acetonitrile in the UHPLC-FD run). The resulting method has high sensitivity, with LODs down to 0.8ngL(-1); adequate intermediate precision, with relative standard deviation values (RSD) always lower than 6.3% (being the range 5.9-9.0% in tap water for a spiked level of 45ngL(-1), 6.1-14% in wastewaters for a spiked level of 45ngL(-1), and 7.2-17% in fruit tea infusion samples for a spiked level of 45ngL(-1)); and adequate relative recoveries, with average values of 82% in tap water, and 94% and 75% in wastewater and fruit tea infusion samples, respectively, if using the proper matrix-matched calibration. PMID- 26852622 TI - Nanoscale Control of Rewriteable Doping Patterns in Pristine Graphene/Boron Nitride Heterostructures. AB - Nanoscale control of charge doping in two-dimensional (2D) materials permits the realization of electronic analogs of optical phenomena, relativistic physics at low energies, and technologically promising nanoelectronics. Electrostatic gating and chemical doping are the two most common methods to achieve local control of such doping. However, these approaches suffer from complicated fabrication processes that introduce contamination, change material properties irreversibly, and lack flexible pattern control. Here we demonstrate a clean, simple, and reversible technique that permits writing, reading, and erasing of doping patterns for 2D materials at the nanometer scale. We accomplish this by employing a graphene/boron nitride heterostructure that is equipped with a bottom gate electrode. By using electron transport and scanning tunneling microscopy (STM), we demonstrate that spatial control of charge doping can be realized with the application of either light or STM tip voltage excitations in conjunction with a gate electric field. Our straightforward and novel technique provides a new path toward on-demand graphene p-n junctions and ultrathin memory devices. PMID- 26852623 TI - Natural Products as Sources of New Drugs from 1981 to 2014. AB - This contribution is a completely updated and expanded version of the four prior analogous reviews that were published in this journal in 1997, 2003, 2007, and 2012. In the case of all approved therapeutic agents, the time frame has been extended to cover the 34 years from January 1, 1981, to December 31, 2014, for all diseases worldwide, and from 1950 (earliest so far identified) to December 2014 for all approved antitumor drugs worldwide. As mentioned in the 2012 review, we have continued to utilize our secondary subdivision of a "natural product mimic", or "NM", to join the original primary divisions and the designation "natural product botanical", or "NB", to cover those botanical "defined mixtures" now recognized as drug entities by the U.S. FDA (and similar organizations). From the data presented in this review, the utilization of natural products and/or their novel structures, in order to discover and develop the final drug entity, is still alive and well. For example, in the area of cancer, over the time frame from around the 1940s to the end of 2014, of the 175 small molecules approved, 131, or 75%, are other than "S" (synthetic), with 85, or 49%, actually being either natural products or directly derived therefrom. In other areas, the influence of natural product structures is quite marked, with, as expected from prior information, the anti-infective area being dependent on natural products and their structures. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are actually produced by microbes and/or microbial interactions with the "host from whence it was isolated", and therefore it is considered that this area of natural product research should be expanded significantly. PMID- 26852624 TI - The within-participant correlation between perception of effort and heart rate based estimations of training load in elite soccer players. AB - The measurement of relative physiological stress during training is important because this is the stimulus for the long-term adaptive response. Measurements of perceived exertion (RPE) have been reported to correlate with the heart rate during field-based training sessions. Nevertheless, there are few studies on how well RPE tracks with the heart rate over repeated training sessions in elite soccer players. Therefore, we aimed to quantify the within-participant correlations between variability in session-RPE (sRPE) and the heart rate in elite male soccer players, and to determine whether the playing position moderated these correlations. The field-based training of four central defenders, four wide defenders, six central midfielders, two wide midfielders and three attackers from an elite English Premier League squad were monitored over an entire in-season competitive period, giving a total of 1010 individual training sessions for study. Correlations between session-RPE and heart rates were quantified using a within-participant model. The correlation between changes in sRPE and heart rates was r = 0.75 (95% CI: 0.71-0.78). This correlation remained high across the various player positions (wide-defender, r = 0.81; central defender, r = 0.74; wide midfielder, r = 0.70; central midfielder, r = 0.70; attacker, r = 0.84; P < 0.001). The correlation between changes in RPE and heart rates, measured during a season-long period of field-based training, is high in a sample of elite soccer players. PMID- 26852625 TI - Automated compared to manual office blood pressure and to home blood pressure in hypertensive patients. AB - We studied the relationships of automated blood pressure (BP), measured in the healthcare centre, with manual office BP and home BP. Stable outpatients treated for hypertension were measured automatically, seated alone in a quiet room, six times after a 5 min rest with the BpTRU device, and immediately afterwards using the auscultatory method. Home BP was measured in a subgroup during 7 days preceding the visit. The automated, office and home BP values were 131.2 +/- 21.8/77.8 +/- 12.1 mmHg, 146.9 +/- 20.8/85.8 +/- 12.4 mmHg and 137.7 +/- 17.7/79.4 +/- 8.2 mmHg, respectively. Limits of agreement between office and automated BP (2 SDs in Bland-Altman plots) were +42.6 to -12.6/+22.6 to -6.6 mmHg for systolic/diastolic BP; for home and automated BP they were +45.8 to 25.8/+20.8 to -12.6 mmHg. For patients with two visits, intraclass correlation coefficients of BP values measured during the first and second visits were 0.66/0.72 for systolic/diastolic automated BP and 0.68/0.74 for systolic/diastolic office BP. Automated BP was lower than home BP and no more closely related to home BP than to office BP. It did not show better repeatability than office BP. Whether automated BP and the "white-coat effect", calculated cas the office BP-automated BP difference, have clinical and prognostic importance deserves further studies. PMID- 26852626 TI - The nutritional property of endosperm starch and its contribution to the health benefits of whole grain foods. AB - Purported health benefits of whole grain foods in lowering risk of obesity, type 2 diabetes, cardiovascular disease, and cancer are supported by epidemiological studies and scientific researches. Bioactive components including dietary fibers, phytochemicals, and various micronutrients present in the bran and germ are commonly considered as the basis for such benefits. Endosperm starch, as the major constituent of whole grains providing glucose to the body, has been less investigated regarding its nutritional property and contribution to the value of whole grain foods. Nutritional quality of starch is associated with its rate of digestion and glucose absorption. In whole grain foods, starch digestion and glucose delivery may vary depending on the form in which the food is delivered, some with starch being rapidly and others slowly digested. Furthermore, there are other inherent factors in whole grain products, such as phenolic compounds and dietary fibers, that may moderate glycemic profiles. A good understanding of the nutritional properties of whole grain starch is important to the development of food processing technologies to maximize their health benefits. PMID- 26852627 TI - Symptomatic Erythrocytosis Due to Homozygosity for Hb Luton [HBA2: c.269A>T (or HBA1)] and alpha-Thalassemia: A Clinical Update. AB - A female proband homozygous for both Hb Luton [alpha89(FG1)His->Leu (CAC>CTC), HBA2: c.269A>T (or HBA1)], a high oxygen affinity hemoglobin (Hb), and for alpha(+)-thalassemia (alpha-thal), (-alpha(4.2), leftward deletion) was first described in 2012. This is a follow-up report of the same case. At the age of 18, the described patient presented with progressively worsening lethargy, headaches, dizziness, syncope and Raynaud's phenomenon. Following extensive cardiological and neurological investigation, it was felt that significant erythrocytosis was the most likely cause. Venesection followed by regular exchange transfusions were arranged with marked amelioration in symptomatology. In the vast majority of cases of high oxygen affinity Hbs, venesection is not recommended due to the asymptomatic phenotype and reduced oxygen delivery resulting from venesection. This update describes the evolving phenotype of this unique proband and, to the best of our knowledge, the first use of regular, long-term therapeutic red cell exchange transfusions in a case of high affinity Hb. PMID- 26852628 TI - A sociological exploration of the tensions related to interprofessional collaboration in acute-care discharge planning. AB - Patient discharge is a key concern in hospitals, particularly in acute care, given the multifaceted and challenging nature of patients' healthcare needs. Policies on discharge have identified the importance of interprofessional collaboration, yet research has described its limitations in this clinical context. This study aimed to extend our understanding of interprofessional interactions related to discharge in a general internal medicine setting by using sociological theories to illuminate the existence of, and interplay between, structural factors and microlevel practices. An ethnographic approach was employed to obtain an in-depth insight into healthcare providers' perspectives, behaviours, and interactions regarding discharge. Data collection involved observations, interviews, and document analysis. Approximately 65 hours of observations were undertaken, 23 interviews were conducted with healthcare providers, and government and hospital discharge documents were collected. Data were analysed using a directed content approach. The findings indicate the existence of a medically dominated division of healthcare labour in patient discharge with opportunities for some interprofessional negotiations; the role of organizational routines in facilitating and challenging interprofessional negotiations in patient discharge; and tensions in organizational priorities that impact an interprofessional approach to discharge. The findings provide insight into the various levels at which interventions can be targeted to improve interprofessional collaboration in discharge while recognizing the organizational tensions that challenge an interprofessional approach. PMID- 26852629 TI - Paracetamol biodegradation by activated sludge and photocatalysis and its removal by a micelle-clay complex, activated charcoal, and reverse osmosis membranes. AB - Kinetic studies on the stability of the pain killer paracetamol in Al-Quds activated sludge demonstrated that paracetamol underwent biodegradation within less than one month to furnish p-aminophenol in high yields. Characterizations of bacteria contained in Al-Quds sludge were accomplished. It was found that Pseudomonas aeruginosa is the bacterium most responsible for the biodegradation of paracetamol to p-aminophenol and hydroquinone. Batch adsorptions of paracetamol and its biodegradation product (p-aminophenol) by activated charcoal and a composite micelle (octadecyltrimethylammonium)-clay (montmorillonite) were determined at 25 degrees C. Adsorption was adequately described by a Langmuir isotherm, and indicated better efficiency of removal by the micelle-clay complex. The ability of bench top reverse osmosis (RO) plant as well as advanced membrane pilot plant to remove paracetamol was also studied at different water matrixes to test the effect of organic matter composition. The results showed that at least 90% rejection was obtained by both plants. In addition, removal of paracetamol from RO brine was investigated by using photocatalytic processes; optimal conditions were found to be acidic or basic pH, in which paracetamol degraded in less than 5 min. Toxicity studies indicated that the effluent and brine were not toxic except for using extra low energy membrane which displayed a half maximal inhibitory concentration (IC-50) value of 80%. PMID- 26852630 TI - Employing the International Classification of Functioning, Disability and Health framework to capture user feedback in the design and testing stage of development of home-based arm rehabilitation technology. AB - The purpose of this study was to evaluate the International Classification of Functioning, Disability and Health (ICF) as a framework to ensure that key aspects of user feedback are identified in the design and testing stages of development of a home-based upper limb rehabilitation system. Seventeen stroke survivors with residual upper limb weakness, and seven healthcare professionals with expertise in stroke rehabilitation, were enrolled in the user-centered design process. Through semi-structured interviews, they provided feedback on the hardware, software and impact of a home-based rehabilitation device to facilitate self-managed arm exercise. Members of the multidisciplinary clinical and engineering research team, based on previous experience and existing literature in user-centred design, developed the topic list for the interviews. Meaningful concepts were extracted from participants' interviews based on existing ICF linking rules and matched to categories within the ICF Comprehensive Core Set for stroke. Most of the interview concepts (except personal factors) matched the existing ICF Comprehensive Core Set categories. Personal factors that emerged from interviews e.g. gender, age, interest, compliance, motivation, choice and convenience that might determine device usability are yet to be categorised within the ICF framework and hence could not be matched to a specific Core Set category. PMID- 26852631 TI - Incidence and risk factors for deep venous thrombosis and pulmonary embolus after liver transplantation. AB - BACKGROUND: Omitting chemical venous thromboembolism prophylaxis in liver transplant recipients may lead to an increase incidence of deep venous thrombosis (DVT) and/or pulmonary embolus (PE). METHODS: A retrospective comparison of liver transplant recipients who developed postoperative DVT/PE to an age-matched population. RESULTS: Forty-three of eight hundred sixty-seven patients developed a DVT/PE. Study group patients received higher amounts of cryoprecipitate and fresh frozen plasma. Study group international normalized ratio (INR) was significantly higher, as was the incidence of postoperative complications. High grade complication rates (bleeding, respiratory failure, and renal insufficiency) were increased in the study group at 16% vs 0%. CONCLUSIONS: The present study demonstrates that the rate of DVT/PE after liver transplantation is similar to the rate after other major operations. Patients were more likely to develop DVT/PE if they received increased amounts of intraoperative cryoprecipitate/fresh frozen plasma (FFP) or had an elevated postoperative INR. Furthermore, patients with a complicated postoperative course have the highest risk of venous thromboembolism. PMID- 26852632 TI - Photodegradation of Oryzalin in aqueous isopropanol and acetonitrile. AB - The phototransformation of Oryzalin was studied under UV light (lambdamax >= 290 nm) and sunlight (lambdamax >= 250 nm) in aqueous isopropanol and acetonitrile solution in absence and presence of TiO2 as sensitizer. The rate of photodegradation of Oryzalin in different solvent system followed first-order kinetics, and calculated half-lives were found to be in the range of 23.52-53.75 h for UV light and 41.23-61.43 h for sunlight. From this study, total 12 photoproducts were identified and characterized on the basis of column chromatography and Q-Tof micromass spectral data. The plausible mechanism of phototransformation involved was hydrolysis, breaking of sulfonic bond, and loss of amino and sulfonic acid group. PMID- 26852633 TI - Heavy-metal-contaminated industrial soil: Uptake assessment in native plant species from Brazilian Cerrado. AB - Plants of the Cerrado have shown some potential for restoration and/or phytoremediation projects due to their ability to grow in and tolerate acidic soils rich in metals. The aim of this study is to evaluate the tolerance and accumulation of metals (Cd, Cu, Pb, and Zn) in five native tree species of the Brazilian Cerrado (Copaifera langsdorffii, Eugenia dysenterica, Inga laurina, Cedrela fissilis, Handroanthus impetiginosus) subjected to three experiments with contaminated soils obtained from a zinc processing industry (S1, S2, S3) and control soil (S0). The experimental design was completely randomized (factorial 5 * 4 * 3) and conducted in a greenhouse environment during a 90-day experimentation time. The plant species behavior was assessed by visual symptoms of toxicity, tolerance index (TI), translocation factor (TF), and bioaccumulation factor (BF). C. fissilis has performed as a Zn accumulator by the higher BFs obtained in the experiments, equal to 3.72, 0.88, and 0.41 for S1, S2, and S3 respectively. This species had some ability of uptake control as a defense mechanism in high stress conditions with the best behavior for phytoremediation and high tolerance to contamination. With economical and technical benefits, this study may support a preliminary analysis necessary for using native tree species in environmental projects. PMID- 26852634 TI - Osteonecrosis of the Hip in Hematologic Disease: A Review of Conditions and Treatment Options. AB - Osteonecrosis of the hip can lead to advanced arthritis in typically young patients. Hematologic disorders comprise one group of potential causes. These include sickle cell anemia, hemophilia, aplastic anemia, thalassemia, and acute lymphoblastic leukemia. Depending on the stage of disease, treatment options include non-operative management, joint-preserving procedures (percutaneous drilling, core decompression, and vascularized or non-vascularized bone grafting), and joint arthroplasty (resurfacing arthroplasty and THA). Numerous small studies have investigated the efficacy of these options in patients who have specific hematologic disorders. Therefore, this report provides a comprehensive review of the osteonecrosis treatment options and results across the spectrum of patients who have various hematologic disorders. PMID- 26852635 TI - Incidence and Future Projections of Periprosthetic Femoral Fracture Following Primary Total Hip Arthroplasty: An Analysis of International Registry Data. AB - As the number of total hip arthroplasties (THA) increases, the number of fractures will increase as well. The purpose of this study was to determine the incidence and prevalence of intra- and post-operative periprosthetic fractures following THA based on national joint registry data and to create a projection model that estimates the future fracture burden. Registry data from multiple joint registries were analyzed. Data on the incidence and prevalence of intra- and post-operative periprosthetic fractures were extracted. The prevalences between individual countries were analyzed to determine the mean prevalence. Three quantitative models were then generated to predict the fracture burden in the United States based on future population trends between 2015 and 2060. The mean incidence of post-operative periprosthetic fractures requiring revision was 0.8% while the incidence of intraoperative fractures was 0.8%. When all revision arthroplasties were assessed, the mean proportion of hips revised due to periprosthetic fracture was 6.6%. Projection models demonstrated that the number of periprosthetic fractures is expected to rise by a mean 4.6% every decade over the next 30 years. Periprosthetic fractures represent a small but important proportion of the revision THA burden worldwide. The incidence of both intra- and post-operative fractures is low, but the number is likely to steadily increase along with the number of surgeries performed. The number of fractures may rise even further as the incidence may potentially be higher in elderly, osteoporotic patients who are likely to represent a greater proportion of the arthroplasty population, particularly. PMID- 26852636 TI - The Risk of Bias in Randomized Trials in General Dentistry Journals. AB - The use of a randomized controlled trial (RCT) research design is considered the gold standard for conducting evidence-based clinical research. In this present study, we aimed to assess the quality of RCTs in dentistry and create a general foundation for evidence-based dentistry on which to perform subsequent RCTs. We conducted a systematic assessment of bias of RCTs in seven general dentistry journals published between January 2011 and March 2012. We extracted study characteristics in duplicate and assessed each trial's quality using the Cochrane Risk of Bias tool. We compared risk of bias across studies graphically. Among 1,755 studies across seven journals, we identified 67 RCTs. Many included studies were conducted in Europe (39%), with an average sample size of 358 participants. These studies included 52% female participants and the maximum follow-up period was 13 years. Overall, we found a high percentage of unclear risk of bias among included RCTs, indicating poor quality of reporting within the included studies. An overall high proportion of trials with an "unclear risk of bias" suggests the need for better quality of reporting in dentistry. As such, key concepts in dental research and future trials should focus on high-quality reporting. PMID- 26852637 TI - Side Effects of Radiation in Bone and Cartilage: An FT-IR Analysis. AB - Although radiation therapy is an essential treatment of cancers, it is associated with unwanted complications. The purpose of this review is to summarize the current knowledge regarding the side effects of radiation in bone and articular cartilage and to recommend Fourier transform infrared spectroscopy to monitor the differences in infrared spectra between healthy and irradiated bone and cartilage. PMID- 26852638 TI - Prospective Case Series of NMES for Quadriceps Weakness and Decrease Function in Patients with Osteoarthritis of the Knee. AB - Osteoarthritis of the knee can lead to substantial disability. The purpose of this study was to evaluate the outcomes of a neuromuscular electrical stimulation (NMES) device in a small case series of treatment of quadriceps muscle weakness and decreased function in patients with knee osteoarthritis. We evaluated isokinetic quadriceps muscle strength, objective functional improvement, subjective functional improvement, quality of life, and pain relief. Patients were then matched with a previously studied cohort with similar osteoarthritic characteristics. Testing demonstrated improvement in isokinetic quadriceps and hamstring muscle strength, as well as several functional and patient-reported metrics. Conversely, patients reported a decrease in Knee Society Score (KSS) functional score, short-form 36 health survey (SF-36), lower extremity functional scale (LEFS), and visual analog scale (VAS) for pain; however, no changes were observed in relation to the mean reported VAS pain score and SF-36 physical component. Control cohort analysis of the patient reported outcomes showed that patients improved from their first visit to 3 months follow-up in functional KSS, SF-36 physical component, and LEFS. However, VAS pain score and objective KSS were unchanged at follow-up. Similarly, a decrease was observed in the scores of the SF-36 mental component. In conclusion, the use of NMES for quadriceps muscle weakness has been shown to improve muscle strength. Additionally, NMES was shown to potentially improve functionality but demonstrated minimal effects on quality of life and patient-reported outcomes compared with the initial visit. However, larger, longer-term, prospective, randomized studies are needed to better evaluate these outcomes. PMID- 26852639 TI - Thirty-Day Readmission Rates Comparing Specific Cruciate Retaining and Posterior Stabilizing Knee Arthroplasties to the National Readmission Rates. AB - Unplanned hospital readmissions within 30 days of surgery result in reimbursement penalties following total knee arthroplasty (TKA). Therefore, evaluating current readmission rates and comparing these to national levels is one way to self assess and determine possible areas where improvements can be made. In this study, the 30-day readmission data for 845 TKAs performed with a single prosthesis were compared to the readmission data from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) Database of 12,035 TKAs. We determined this following: (1) whether the TKA groups readmission rates were comparable; (2) the similarities and differences between readmission causes between the cohorts; and (3) the patient factors associated with increased readmission rates. The 30-day readmission rate for our cohort was lower than the NSQIP rate (2.1% versus 4.3%, respectively). Among all readmissions, our database had fewer readmissions due to surgically related complications (44% versus 57%, respectively). Patients in the single-prosthesis database had higher body mass indexes and higher rates of cardiovascular disorders, diabetes, and musculoskeletal disease. Within the NSQIP cohort, a higher proportion of males than females were readmitted. The most common comorbidities in the readmitted cohort were diabetes, chronic obstructive pulmonary disease, cardiac surgery, hypertension, bleeding disorders, and American Society of Anesthesiologists (ASA) grade 3. Of the surgically related factors, readmitted patients had significantly longer operative procedures. The 30-day readmission rate for patients undergoing primary TKAs in our database was lower than that of a national database. PMID- 26852640 TI - Risk Factors Associated with Adjacent and Remote- Level Pathologic Vertebral Compression Fracture Following Balloon Kyphoplasty: 2-Year Follow-Up Comparison Versus Conservative Treatment. AB - Vertebral compression fractures are a significant source of morbidity and mortality among patients of all age groups. These fractures result in both acute and chronic pain. Patients who sustain such fractures are known to suffer from more comorbidities and have a higher mortality rate compared with healthy people in the same age group. In recent years, balloon kyphoplasty has become a popular method for treating vertebral compression fractures. However, as longer-term follow-up becomes available, the effects of cement augmentation on adjacent spinal segments require investigation. Here, we have performed a retrospective chart review of 258 consecutive patients with pathologic vertebral compression fractures secondary to osteoporosis, treated by either conservative measures or balloon kyphoplasty with polymethylmethacrylate cement augmentation. Multivariate analysis of patient comorbidities was performed to assess the risks associated with subsequent adjacent and remote compression fracture at a minimum of 2 years follow-up. A total of 258 patients had 361 vertebral compression fractures. A total of 121 patients were treated nonoperatively and 137 underwent balloon kyphoplasty with polymethylmethacrylate cement augmentation. The mean follow-up for both cohorts was 2.7 years (range, 2-6 years). The kyphoplasty cohort was significantly older than the nonoperative cohort (mean age, 78.5 versus 74.2 years; p = 0.02), had 24 more patients with diabetes mellitus (37 versus 13; p = 0.05), and had 34 more patients with a history of smoking (50 versus 16; p = 0.05). However, the kyphoplasty cohort had less patients with a history of non steroidal anti-inflammatory drug (NSAID) use (45 versus 71; p = 0.07). There were no demographic differences between groups in patients with secondary fractures. Nonoperative treatment was identified as a statistically significant independent risk factor for subsequent vertebral compression fracture [odds ratio (OR), 2.28]. Univariate analysis identified age, diabetes mellitus, smoking, NSAID usage, and female gender as risk factors for subsequent vertebral compression fracture. When adjusted for multivariate analysis, no individual factor demonstrated increased risk for subsequent fracture. Patients diagnosed with vertebral compression fractures secondary to osteoporosis suffer from multiple medical comorbidities. No particular comorbidity was identified as solely attributable for increased risk of subsequent remote or adjacent compression fractures. Patients in this series treated with nonoperative (conservative) management had a 2.28 times greater risk for a subsequent vertebral compression fracture than patients treated with balloon kyphoplasty and polymethylmethacrylate cement augmentation. PMID- 26852641 TI - Is Gelsolin a Biomarker for Aseptic Loosening After Total Knee Arthroplasty? AB - Gelsolin (GSN) has been implicated in inflammatory reactions in asthmatic patients and may be a marker for acute or chronic reactions in synovial tissue. Detection of increased levels of GSN in synovial fluid could differentiate between aseptic loosening (low GSN) and hypersensitivity reaction (high GSN). Synovial fluid from both knees of 7 cadaver specimens with unilateral TKA was analyzed using ELISA for GSN levels. Components were explanted after spiral CT scans to determine wear patterns and loosening. Results were compared to synovial fluid from 7 consecutive TKA revisions for aseptic failure. Average GSN levels for cadaver native and well-functioning TKA knees were 24,534+/-10,437 ng/mL and 38,430+/-30,907 ng/mL, respectively (p=0.314). Average GSN level for revision patients was 53,294+/-19,868 ng/mL, significantly higher than cadaver well functioning TKAs (p=0.006). The patient with the highest level of GSN at time of revision surgery showed significant metallosis at the time of surgery. PMID- 26852642 TI - What are the Risk Factors for Hardware Removal After Tibia or Fibula Fracture? AB - Indications for open reduction and internal fixation (ORIF) of tibia and/or fibula fractures vary; however, some patients require removal of hardware (ROH) due to various complications. Currently, data evaluating the epidemiology of and risk factors for ROH of the tibia/fibula are limited. We examined the associations between tibia/fibula fractures and (1) characteristics of fractures requiring ORIF, (2) indications for ROH, (3) demographic risk factors for ROH; (4) length of stay, and (5) total hospital charges. The Nationwide Inpatient Sample (NIS) was used to identify patients admitted for tibia/fibula ORIF and ROH between 1998 and 2010 in the United States. We used ICD-9 codes to identify fracture locations, comorbidities, and indications for ROH. We identified 1,610,149 ORIF patients, and 56,864 of these patients (3.5%) underwent ROH. Logistic regression analyses and independent sample t-tests were used to assess risk factors and differences. Among fractures requiring ORIF, the most common were for closed fractures of both tibia and fibula. The most common indications for ROH were infection and osteomyelitis. Risk factors for ROH included men and Deyo comorbidity scores of 1 and 2 or more. Age and race were not risk factors for ROH. The length of stay and total charges were significantly higher for ROH compared to those with ORIF only. Hardware removal is a serious complication following ORIF for fractures of the tibia/fibula. The results of the current study suggest that gender, presence of comorbidities, and payer status were all significant factors in predicting hardware removal for the tibia/fibula following ORIF. PMID- 26852643 TI - Static and Dynamic Bracing for Loss of Motion Following Total Knee Arthroplasty. AB - Pain and dysfunction leading to decreased range-of-motion following total knee arthroplasty (TKA) is a common complication that may require treatment beyond standard rehabilitation efforts. In this review, we discuss the use of static and dynamic stretch devices to treat these range-of-motion dysfunctions. There are two mechanisms by which these devices work: dynamic stretch applies a constant low force, which allows for a variable soft-tissue displacement as they stretch, and static progressive stretch increases displacement, which allows for a constant displacement at a variable force leading to tissue stress relaxation. The uses of both devices have been reported to be effective in treating range-of motion dysfunction after TKA. These devices are excellent options for the treatment of TKA stiffness, but they may undergo even further refinement in the future, as more information about exact indications and device modification emerge. PMID- 26852644 TI - TREM-1, a negative regulator of human osteoclastogenesis. AB - Triggering receptor expressed on myeloid cells (TREMs) are a family of cell surface receptors that play important roles in innate and adaptive immunity. Among them, TREM-2 has been extensively studied for its role in osteoclast differentiation and its essential role in human osteoclastogenesis has been well established. However, much less has been discovered about the role of TREM-1 in human osteoclast differentiation. In this study, we investigate the role of TREM 1 in human osteoclast differentiation. Consistent with previous reports, TREM-2 expression was strongly increased during the generation of human osteoclast precursors. In contrast, TREM-1 expression was decreased during the generation of human osteoclast precursors. Stimulation of TREM-1 using agonistic anti-TREM-1 antibody resulted in suppression of RANKL-induced osteoclastogenesis, as evidenced by diminished formation of TRAP+ multinucleated cells. In addition, TREM-1 stimulation strongly suppressed RANKL-induced expression of osteoclast related genes such as cathepsin K and NFATc1. TREM-1 stimulation also down regulated gene expression and cell surface expression of M-CSF receptor that is essential for osteoclast differentiation and survival. In synovial fluid macrophages of rheumatoid arthritis (RA) patients, TREM-1 stimulation suppressed osteoclastogenesis. In conclusion, we demonstrate that TREM-1 acts as a negative regulator of human osteoclast differentiation and identify a novel mechanism of negative regulation of osteoclastogenesis that plays a role in inflammation. PMID- 26852645 TI - Rates and Patterns of Comorbidity Among First-Year College Students With ADHD. AB - The purpose of this study was to examine rates and patterns of non-attention deficit/hyperactivity disorder (non-ADHD) psychiatric diagnoses among a large group of 1st-year college students with and without ADHD. A total of 443 participants, including 214 men and 229 women ranging in age from 18 to 22 years of age (M = 18.2), were recruited from 9 colleges involved in a large-scale, multisite longitudinal investigation. Non-Hispanic Caucasian students represented 67.5% of the total sample. A comprehensive multimethod assessment approach was used in conjunction with expert panel review to determine both ADHD and comorbidity status. Significantly higher rates of overall comorbidity were found among college students with well-defined ADHD, with 55.0% exhibiting at least one comorbid diagnosis and 31.8% displaying two or more, relative to the corresponding rates of non-ADHD diagnoses among Comparison students, which were 11.2% and 4.0%, respectively. These differences in overall comorbidity rates were, in large part, attributable to the increased presence of depressive and anxiety disorders, especially major depressive disorder (active or in partial remission) and generalized anxiety disorder, among the students with ADHD. Within the ADHD group, differential comorbidity rates were observed as a function of ADHD presentation type and gender but not ethnic/racial diversity status. The current findings fill a gap in the literature and shed new light on the rates and patterns of comorbidity among emerging adults with ADHD in their 1st year of college. Implications for providing clinical and support services to college students with ADHD are discussed. PMID- 26852646 TI - [A comparison of different densities of levobupivacaine solutions for unilateral spinal anaesthesia]. AB - BACKGROUND AND OBJECTIVES: The aim of the study was to compare the block characteristics and clinical effects of dextrose added to levobupivacaine solutions at different concentrations to provide unilateral spinal anaesthesia in lower extremity surgery. METHODS: This prospective, randomised, double-blind study comprised 75 ASA I-II risk patients for whom unilateral total knee arthroscopy was planned. The patients were assigned to three groups: in Group I, 60mg dextrose was added to 7.5mg of 0.5% levobupivacaine, in Group II, 80mg and in Group III, 100mg. Spinal anaesthesia was applied to the patient in the lateral decubitus position with the operated side below and the patient was kept in position for 10min. RESULTS: The time for the sensorial block to achieve T12 level was slower in Group I than in Groups II and III (p<0.05, p<0.00). The time to full recovery of the sensorial block was 136min in Group I, 154min in Group II and 170min in Group III. The differences were statistically significant (p<0.05). The mean duration of the motor block was 88min in Group I, 105min in Group II, and 139min in Group III and the differences were statistically significant (p<0.05). The time to urination in Group I was statistically significantly shorter than in the other groups (p<0.00). CONCLUSIONS: The results of the study showed that together with an increase in density, the sensory and motor block duration was lengthened. It can be concluded that 30mgmL(-1) concentration of dextrose added to 7.5mg levobupivacaine is sufficient to provide unilateral spinal anaesthesia in day-case arthroscopic knee surgery. PMID- 26852647 TI - The distribution of hand fractures at the university hospital of north Norway. AB - BACKGROUND: The objective of this study was to describe the fracture pattern for hand fractures in the Arctic region of Norway. MATERIALS AND METHODS: Using the hospital's radiological information system and picture archiving and communication system all traumatic hand fractures in the year of 2010 were registered. Fractures in the carpal, metacarpal, and phalangeal bones were included in the study. RESULTS: A total of 593 patients with 691 fractures including 80 carpal, 200 metacarpal, and 411 phalangeal fractures were registered. The most commonly affected bone was the 5th metacarpal bone with a total of 99 fractures (14%), 22 of these (22%) were classified as subcapital or "boxer's fracture". Among male patients, the highest frequency of fractures was seen in the age group 10-60 years with a peak between 10-24 years. Adult female patients had most fractures in the age group 50-70 years. Generally, there were no seasonal variations, although a marked decrease of fractures could be seen in December. Triquetral fractures were more common during the winter season. Falling was the most common trauma mechanism. CONCLUSION: With a few exceptions, hand fractures were not related to particular seasons or weekdays in this material. The distribution of hand fractures was related to age and gender, and some trauma mechanisms were dominating. PMID- 26852648 TI - Serum apelin as a novel non-invasive marker for subclinical cardiopulmonary complications in children and adolescents with sickle cell disease. AB - BACKGROUND: Cardiovascular involvement represents a leading cause of mortality and morbidity in sickle cell disease (SCD). Apelin is a peptide involved in the regulation of cardiovascular function. AIM: To determine serum apelin among 40 children and adolescents with SCD compared with 40 healthy controls and assess its relation to markers of hemolysis, iron overload as well as cardiopulmonary complications. METHODS: SCD patients, in steady state and asymptomatic for heart disease, were studied stressing on hydroxyurea/chelation therapy, hematological profile, serum ferritin and apelin levels. Full echocardiographic study including assessment of biventricular systolic function and pulmonary artery pressure was done. RESULTS: Apelin levels were significantly lower in SCD patients compared with controls (P<0.001). Cardiopulmonary complications were encountered in 30% of patients. Apelin was significantly decreased among patients with cardiopulmonary disease (P=0.006) whether those at risk of pulmonary hypertension (P=0.018) or patients with heart disease (P=0.043). Hydroxyurea-treated patients had higher apelin levels than untreated ones (P=0.001). Apelin was negatively correlated to lactate dehydrogenase, indirect bilirubin, serum ferritin, end systolic diameter, tricuspid regurgitant jet velocity, right ventricle systolic pressure, pulmonary vascular resistance and tissue Doppler imaging S wave. Apelin cutoff value of 1650ng/L could significantly detect the presence of cardiopulmonary complications in SCD with 90.9% sensitivity and 72.4% specificity. CONCLUSION: Apelin is a promising marker for screening of SCD patients at risk of cardiopulmonary disease because it is altered during the early subclinical stage of cardiac affection. A combination of apelin and echocardiography provides a reliable method to assess cardiopulmonary affection in young SCD patients. PMID- 26852649 TI - Heterozygous congenital Factor VII deficiency with the 9729del4 mutation, associated with severe spontaneous intracranial bleeding in an adolescent male. AB - BACKGROUND: In congenital Factor (F) VII deficiency bleeding phenotype and intrinsic FVII activity levels don't always correlate. Patients with FVII activity levels <30% appear to have a higher bleeding propensity, but bleeding can also occur at higher FVII activity levels. Reasons for bleeding at higher FVII activity levels are unknown, and it remains challenging to manage such patients clinically. CASE: A 19year old male with spontaneous intracranial hemorrhage and FVII activity levels of 44%, requiring emergent surgical intervention and a strategy for FVII replacement. Genotyping showed the rare heterozygous FVII 9729del4 mutation. Bleed evacuation was complicated by epidural abscess requiring craniectomy, bone graft procedures, and prolonged administration of recombinant human (rh) activated FVII (FVIIa). The patient recovered without neurological deficits, and remains on prophylactic low dose treatment with rhFVIIa in relation to risky athletic activities. CONCLUSION: For clinicians, it is important to recognize that effects of rhFVIIa within these pathways are independent of its contribution to blood clot formation and cannot be assessed by clotting assays. Reduced FVII levels should therefore not be dismissed, as even a mild reduction may result in spontaneous bleeding. Treatment of mild FVII deficiency requires a careful case-by-case approach, based on the clinical scenario. PMID- 26852650 TI - Interaction of CARD14, SENP1 and VEGFA polymorphisms on susceptibility to high altitude polycythemia in the Han Chinese population at the Qinghai-Tibetan Plateau. AB - High altitude polycythemia (HAPC) is a serious public health problem among Han Chinese immigrants to the Qinghai-Tibetan Plateau. This study aims to explore the genetic basis of HAPC in the Han Chinese population. 484 male subjects (234 patients and 250 controls) were enrolled in this study. Genotyping was performed for polymorphisms of I/D in ACE, C1772T and G1790A in exon 12 of HIF-1alpha, rs2567206 in CYP1B1, rs726354 in SENP1, rs3025033 in VEGFA, rs7251432 in HAMP, rs2075800 in HSPA1L and rs8065364 in CARD14. Gene-gene interaction was assessed by multifactor dimensionality reduction. A significant association was seen between CARD14 polymorphism rs8065364 and risk of HAPC development in male Han Chinese, and the C allele of rs8065364 was a risk factor (odds ratio (OR)=1.59, 95% confidence interval (95% CI)=1.21-2.08). Gene-gene interaction analysis indicated that a synergistic relationship existed between rs3025033 and rs8065364 (1.00%), rs3025033 and rs726354 (0.18%), and rs726354 and rs8065364 (0.17%). The combination of rs8065364 in CARD14, rs3025033 in VEGFA and rs726354 in SENP1 was the best model to predict HAPC development in this study (testing accuracy=0.6183, p=0.0010, cross-validated consistency=10/10). Genetic interactions of SNPs in CARD14, SENP1 and VEGFA might represent a functional mechanism in the pathogenesis of HAPC. PMID- 26852651 TI - Optimising iron chelation therapy with deferasirox for non-transfusion-dependent thalassaemia patients: 1-year results from the THETIS study. AB - Efficacy and safety of iron chelation therapy with deferasirox in iron-overloaded non-transfusion-dependent thalassaemia (NTDT) patients were established in the THALASSA study. THETIS, an open-label, single-arm, multicentre, Phase IV study, added to this evidence by investigating earlier dose escalation by baseline liver iron concentration (LIC) (week 4: escalation according to baseline LIC; week 24: adjustment according to LIC response, maximum 30mg/kg/day). The primary efficacy endpoint was absolute change in LIC from baseline to week 52. 134 iron-overloaded non-transfusion-dependent anaemia patients were enrolled and received deferasirox starting at 10mg/kg/day. Mean actual dose+/-SD over 1year was 14.70+/ 5.48mg/kg/day. At week 52, mean LIC+/-SD decreased significantly from 15.13+/ 10.72mg Fe/g dw at baseline to 8.46+/-6.25mg Fe/g dw (absolute change from baseline, -6.68+/-7.02mg Fe/g dw [95% CI: -7.91, -5.45]; P<0.0001). Most common drug-related adverse events were gastrointestinal: abdominal discomfort, diarrhoea and nausea (n=6 each). There was one death (pneumonia, not considered drug related). With significant and clinically relevant reductions in iron burden alongside a safety profile similar to that in THALASSA, these data support earlier escalation with higher deferasirox doses in iron-overloaded non transfusion-dependent anaemia patients. PMID- 26852652 TI - ETV6/RUNX1 transcript is a target of RNA-binding protein IGF2BP1 in t(12;21)(p13;q22)-positive acute lymphoblastic leukemia. AB - The oncofetal RNA-binding protein IGF2BP1 (IGF2 mRNA binding protein 1) is overexpressed in a subset of cancers and promotes cell cycle, migration and aggressive phenotype by regulating post-transcriptionally a number of key mRNAs (e. g, ACTB, CD44, CTNNB1, KRAS, MAPK4, MYC, PTEN and others). IGF2BP1 is also overexpressed in t(12;21)(p13;q22)-positive acute lymphoblastic leukemia (ALL), but the biological significance of this phenomenon has not been addressed so far. We have identified leukemia fusion gene ETV6/RUNX1 mRNA to be highly enriched in immunoprecipitated fraction of endogenous IGF2BP1 from a model cell line REH and t(12;21)(p13;q22)-positive ALL samples. Furthermore, downregulation of IGF2BP1 by two-fold has resulted in a corresponding decrease of ETV6/RUNX1 mRNA validating this transcript as a target of IGF2BP1 protein in t(12;21)(p13;q22)-positive ALL. These data infer that IGF2BP1 is a potent regulator of ETV6/RUNX1 mRNA stability and potentially link this evolutionary-highly conserved protein to cell transformation events in ETV6/RUNX1-mediated leukemogenesis of t(12;21)(p13;q22) positive ALL. PMID- 26852654 TI - Analysis of clinical and immunophenotypic features along with treatment outcomes of diffuse large B cell lymphoma patients, based on the involvement of nodal or extranodal primary sites. AB - AIMS: The aim of the present study was to elucidate the clinical features, immunophenotype and treatment outcomes of diffuse large B cell lymphoma (DLBCL) patients based on the involvement of the primary site i.e. lymph node or specific extranodal sites. METHODS: We analyzed the clinical characteristics, immunophenotype and treatment outcomes of 207 DLBCL patients diagnosed in China between 2007 and 2014 based on the primary site of location. RESULTS: Based on the involvement of primary site of occurrence, DLBCL cases, were classified into different groups like, lymph node (60 cases, 28.98%), gastrointestinal tract (GI) (53 cases, 25.60%), Waldeyer's ring (WR) (31 cases, 14.97%), gland (25 cases, 12.08%), and other extranodal sites (38 cases, 18.36%). Patients with WR involvement were more frequently associated with early stage disease, favorable performance status, absence of bulky disease, normal LDH and ESR levels, and low- or low/intermediate-risk IPI than the other groups. The proportion of DLBCL patients with germinal center B cell (GCB) phenotype was 56.0% for WR, 46.5% for GI, 34.5% for lymph node, 27.8% for other extranodal sites, and 18.2% for gland (P=0.035). The 5-year overall survival (OS) of the entire patient population was 71.1%, and WR group showed a better outcome than nodal group (84.9% vs. 55.9%, P=0.015). In multivariate analysis, bulky disease, bone marrow infiltration, non GCB phenotype, intermediate/high- or high-risk IPI and SD/PD/Death after first therapy were identified as independent factors for poor OS, while regular application of rituximab and remission after first therapy were identified as favorable prognostic factors for PFS. CONCLUSIONS: In this study, WR involvement was associated with more favorable clinical & pathological features along with better outcome than nodal lymphoma. The OS and PFS were largely dependent on other prognostic variables such as IPI or immunophenotype instead of the sites of involvement. PMID- 26852653 TI - Evaluation of treatment response to enzyme replacement therapy with Velaglucerase alfa in patients with Gaucher disease using whole-body magnetic resonance imaging. AB - OBJECTIVE: This was a retrospective data analysis to evaluate the treatment response to enzyme replacement therapy (ERT) with Velaglucerase alfa using whole body magnetic resonance imaging (MRI). MATERIALS AND METHODS: A baseline and follow-up MRI were performed on 18 Gaucher Type 1 patients at an interval of 11.6 months. The MRI score systems determined the Bone-Marrow-Burden (BMB) score, the Dusseldorf-Gaucher score (DGS), and the Vertebra-Disc-Ratio (VDR). The Severity Score Index Type 1 (GD-DS3) was also assessed. RESULTS: The baseline MRI medians were: BMB, 7.00; DGS, 3.00; and VDR: 1.70; while, the follow-up MRI medians were: BMB, 7.00; DGS, 3.00; and VDR: 1.73. The baseline GD-DS3 median was 2.40 (BMB excl.: 0.50) and the follow-up median was 2.00 (BMB excl.: 0.50). There was weak statistical significance with the Wilcoxon signed-rank test for the DGS (p=0.034) and GD-DS3 (p=0.047) between both MRIs. CONCLUSION: Velaglucerase alfa therapy is a effective long-term treatment for Gaucher Type 1 patients who are newly diagnosed or switching therapies. Measurements with whole-body MRI and an objective scoring system were reliable tools for detecting early stage bone marrow activity. Further research is needed to evaluate the "Booster-Effect" of Velaglucerase alfa therapy in Gaucher skeletal disease. PMID- 26852655 TI - Genome-wide association study of serum iron phenotypes in premenopausal women of European descent. AB - A genome-wide association study was performed on 1130 premenopausal women to detect common variants associated with three serum iron-related phenotypes. Total iron binding capacity was strongly associated (p=10(-14)) with variants in and near the TF gene (transferrin), the serum iron transporting protein, and with variants in HFE (p=4*10(-7)), which encodes the human hemochromatosis gene. Association was also detected between percent iron saturation (p=10(-8)) and variants in the chromosome 6 region containing both HFE and SLC17A2, which encodes a phosphate transport protein. No significant associations were detected with serum iron, but variants in HFE were suggestive (p=10(-6)). Our results corroborate prior studies in older subjects and demonstrate that the association of these genetic variants with iron phenotypes can be detected in premenopausal women. PMID- 26852656 TI - Association of TNF polymorphisms with JAK2 (V617F) myeloproliferative neoplasms in Brazilian patients. AB - The classical chromosome Philadelphia-negative myeloproliferative neoplasms (MPNs) are a group of disorders that share clinical, hematological, and histological features. Proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) are elevated in patients with MPN. The aim of this study was to verify the association between the polymorphisms of TNF gene (-308G/A and -238 G/A) in BCR-ABL-negative MPN in our population. Blood samples obtained from MPN patients were genotyped for the JAK2V617F mutation and both TNF polymorphisms using PCR-RFLP. Thirty three (26.8%) patients with polycythemia vera (PV), 35 (28.7%) essential thrombocythemia (ET), 22 (17.7%) primary myelofibrosis (PMF), and 33 (26.8%) with unclassifiable MPN (MPNu) were included in the study. The JAK2 V617F mutation was detected in 94 (76.42%) patients. Were observed a significant increase on the frequency of the TNF-238 GA genotype in MPN patients compared to controls (OR=2.21, 95% CI=1.02-4.80, P<0.04). The distribution of the genotypes and allelic frequencies of TNF-308 was significantly different among the MPNs, JAK2V617F positive, PV and PMF, and controls. Our data has demonstrated that the polymorphisms on TNF-238 GA, TNF-308 GA were associated to MPN development in this population, triggered by JAK2 V617F mutation. PMID- 26852657 TI - Quantification of pain in sickle mice using facial expressions and body measurements. AB - Pain is a hallmark feature of sickle cell disease (SCD). Subjects typically quantify pain by themselves, which can be biased by other factors leading to overtreatment or under-treatment. Reliable and accurate quantification of pain, in real time, might enable to provide appropriate levels of analgesic treatment. The mouse grimace scale (MGS), a standardized behavioral coding system with high accuracy and reliability has been used to quantify varied types of pain. We hypothesized that addition of the objective parameters of body length and back curvature will strengthen the reproducibility of MGS. We examined MGS scores and body length and back curvature of transgenic BERK sickle and control mice following cold treatment or following treatment with analgesic cannabinoid CP55,940. We observed that sickle mice demonstrated decreased length and increased back curvature in response to cold. These observations correlate with changes in facial expression for the MGS score. CP55,940 treatment of sickle mice showed an increase in body length and a decrease in back curvature concordant with MGS scores indicative of an analgesic effect. Thus, body parameters combined with facial expressions may provide a quantifiable unbiased method for objective measure of pain in SCD. PMID- 26852658 TI - No evidence for cell activation or brain vaso-occlusion with plerixafor mobilization in sickle cell mice. AB - Gene therapy for sickle cell disease is currently in active trials. Collecting hematopoietic progenitor cells safely and effectively is challenging, however, because granulocyte colony stimulating factor, the drug used most commonly for mobilization, can cause life-threatening vaso-occlusion in patients with sickle cell disease, and bone marrow harvest requires general anesthesia and multiple hip bone punctures. Plerixafor is an inhibitor of the CXCR4 chemokine receptor on hematopoietic progenitor cells, blocking its binding to SDF-1 (CXCL12) on bone marrow stroma. In support of a clinical trial in patients with sickle cell disease of plerixafor mobilization (NCT02193191), we administered plerixafor to sickle cell mice and found that it mobilizes hematopoietic progenitor cells without evidence of concomitant cell activation or brain vaso-occlusion. PMID- 26852659 TI - Sibling cord blood donor program for hematopoietic cell transplantation: the 20 year experience in the Rome Cord Blood Bank. AB - Umbilical cord blood (UCB) represents a source of hematopoietic stem cells for patients lacking a suitably matched and readily available related or unrelated stem cell donor. As UCB transplantation from compatible sibling provides good results in children therefore directed sibling UCB collection and banking is indicated in family who already have a child with a disease potentially treatable with an allogeneic hematopoietic stem cell transplantation. Particularly, related UCB collection is recommended when the patients urgently need a transplantation. To provide access to all patients in need, we developed a "Sibling cord blood donor program for hematopoietic cell transplantation". Here we report results of this project started 20years ago. To date, in this study a total of 194 families were enrolled, a total of 204 UCB samples were successfully collected and 15 pediatric patients have been transplanted. Recently, some authors have suggested novel role for UCB other than in the transplantation setting. Therefore, future studies in the immunotherapy and regenerative medicine areas could expand indication for sibling directed UCB collection. PMID- 26852661 TI - Genetic basis of severe factor XIII deficiency in a large cohort of Indian patients: Identification of fourteen novel mutations. AB - Congenital factor XIII (FXIII) deficiency, the most under diagnosed disorder is caused mainly due to underlying defects in the catalytic A subunit of FXIII. More than 100 mutations throughout the factor XIII A gene (F13A1) have been identified so far. Present study aims to characterize the molecular basis of severe congenital FXIII deficiency in a large series of patients from different parts of India. F13A1 defects were identified in 37 severe FXIII deficient unrelated Indian patients by direct DNA sequencing. 25 mutations were detected, of which 10 were missense, 9 nonsense, 3 splice site and 3 deletions; 14 were novel. This is the largest series of FXIII deficient cases reported from India in which mutations were analysed with high heterogeneity in the nature of mutations along with several common mutations. PMID- 26852660 TI - Immunophenotyping with CD135 and CD117 predicts the FLT3, IL-7R and TLX3 gene mutations in childhood T-cell acute leukemia. AB - With the combination of immunophenotyping and molecular tests, it is still a challenge to identify the characteristics of T cell acute lymphoblastic leukemia (T-ALL) associated with distinct outcomes. This study tests the possible correlation of cellular expression of CD135 and CD117 with somatic gene mutations in T-ALL. One hundred sixty-two samples were tested, including 143 at diagnosis, 15 from T-lymphoblastic lymphoma at relapse, and four relapse samples from sequential follow-up of T-ALL. CD135 and CD117 monoclonal antibodies were included in the T-ALL panel of flow cytometry. The percentage of cells positivity and the median fluorescence intensity were correlated with gene mutational status. STIL-TAL1, TLX3, FLT3 and IL7R mutations were tested using standard techniques. STIL-TAL1 was found in 24.8%, TLX3 in 12%, IL7R in 10% and FLT3-ITD in 5% of cases. FLT3 and IL7R mutations were mutually exclusive, as were FLT3-ITD and STIL-TAL1. Associations of CD135(high) (p<0.01), CD117(intermediate/high) (p=0.02) and FLT3-ITD, CD117(low) with IL7R(mutated) (p<0.01) and CD135(high) with TLX3(pos) were observed. We conclude that the addition of CD135 and CD117 to the diagnosis can predict molecular aberrations in T-ALL settings, mainly segregating patients with FLT3-ITD, who would benefit from treatment with inhibitors of tyrosine. PMID- 26852662 TI - Substance P enhances tissue factor release from granulocyte-macrophage colony stimulating factor-dependent macrophages via the p22phox/beta-arrestin 2/Rho A signaling pathway. AB - Granulocyte-macrophage colony stimulating factor (GM-CSF) induces procoagulant activity of macrophages. Tissue factor (TF) is a membrane-bound glycoprotein and substance P (SP) is a pro-inflammatory neuropeptide involved in the formation of membrane blebs. This study investigated the role of SP in TF release by GM-CSF dependent macrophages. SP significantly decreased TF levels in whole-cell lysates of GM-CSF-dependent macrophages. TF was detected in the culture supernatant by enzyme-linked immunosorbent assay after stimulation of macrophages by SP. Aprepitant (an SP/neurokinin 1 receptor antagonist) reduced TF release from macrophages stimulated with SP. Pretreatment of macrophages with a radical scavenger(pyrrolidinedithiocarbamate) also limited the decrease of TF in whole cell lysates after stimulation with SP. A protein kinase C inhibitor (rottlerin) partially blocked this macrophage response to SP, while it was significantly inhibited by a ROCK inhibitor (Y-27632) or a dynamin inhibitor (dinasore). An Akt inhibitor (perifosine) also partially blocked this response. Furthermore, siRNA targeting p22phox, beta-arrestin 2, or Rho A, blunted the release of TF from macrophages stimulated with SP. In other experiments, visceral adipocytes derived from cryopreserved preadipocytes were found to produce SP. In conclusion, SP enhances the release of TF from macrophages via the p22phox/beta-arrestin 2/Rho A signaling pathway. PMID- 26852663 TI - Regulatory B cells (CD19(+)CD38(hi)CD24(hi)) in alloimmunized and non alloimmunized children with beta-thalassemia major. AB - BACKGROUND: beta-Thalassemia major (BTM) is considered the most common hemoglobinopathy in Egypt and is one of the major health problems in our locality. MATERIALS & METHODS: We investigated the frequency of B-regulatory cells (CD19(+)CD38(hi)CD24(hi)); (Bregs) among polytransfused alloimmunized and non-alloimmunized children with BTM. The study included 110 polytransfused pediatric patients with beta-thalassemia major. Clinical and transfusion records of all studied patients were reviewed. Indirect antiglobulin test was performed to detect the presence of alloantibodies. We used flow cytometry for detection of CD19(+)CD38(hi)CD24(hi) regulatory B cells. RESULTS: Alloimmunization was detected in 35.5% of thalassemic patients (39/110). The analysis of our data showed a significantly higher frequency of Bregs (CD19(+)CD38(hi)CD24(hi)) in the peripheral blood of both alloimmunized and non-alloimmunized patients as compared to healthy controls. CONCLUSIONS: Our data showed that the frequencies of CD19(+)CD24(hi)CD38(hi) Bregs cells were significantly increased in children with BTM. Our data suggested that Bregs cells could play a role in the clinical course of BTM. The relationship of Bregs to immune disorders in BTM children remains to be determined. Further longitudinal study with a larger sample size is warranted to explore the mechanisms of Breg cells in the disease process in BTM patients. PMID- 26852664 TI - BRAT1 and TSEN54: Important Roles in Basic Cellular Processes and Similar Phenotypes. PMID- 26852665 TI - Long-term daily vibration exposure alters current perception threshold (CPT) sensitivity and myelinated axons in a rat-tail model of vibration-induced injury. AB - Repeated exposure to hand-transmitted vibration through the use of powered hand tools may result in pain and progressive reductions in tactile sensitivity. The goal of the present study was to use an established animal model of vibration induced injury to characterize changes in sensory nerve function and cellular mechanisms associated with these alterations. Sensory nerve function was assessed weekly using the current perception threshold test and tail-flick analgesia test in male Sprague-Dawley rats exposed to 28 d of tail vibration. After 28 d of exposure, Abeta fiber sensitivity was reduced. This reduction in sensitivity was partly attributed to structural disruption of myelin. In addition, the decrease in sensitivity was also associated with a reduction in myelin basic protein and 2',3'- cyclic nucleotide phosphodiasterase (CNPase) staining in tail nerves, and an increase in circulating calcitonin gene-related peptide (CGRP) concentrations. Changes in Abeta fiber sensitivity and CGRP concentrations may serve as early markers of vibration-induced injury in peripheral nerves. It is conceivable that these markers may be utilized to monitor sensorineural alterations in workers exposed to vibration to potentially prevent additional injury. PMID- 26852667 TI - What leads some people to think they are HIV-positive before knowing their diagnosis? A systematic review of psychological and behavioural correlates of HIV risk perception. AB - Current HIV-risk perception refers to the extent to which individuals think they might be HIV-positive. This belief, distinct from the perceived risk about being infected with HIV in the future, is likely to have a range of important consequences. These consequences may include both psychological effects (e.g., impacts on well-being) and behavioural effects (e.g., HIV testing uptake). Given these possible outcomes, and the suggested importance of risk perception in health behaviour models, understanding the behavioural and psychological antecedents of current HIV-risk perception is crucial. This systematic review investigates the relationship between behavioural and psychological factors and current HIV-risk perception (in individuals who are unaware of their actual HIV status). Eight studies were eligible for inclusion in the review (five quantitative and three qualitative studies). Drug risk behaviour and sexual risk behaviour (both self and partner) were often associated with current HIV-risk perception, although other studies failed to show a relationship between one's own sexual risk behaviour and risk perception. Psychological factors were only rarely assessed in relation to current HIV-risk perception. Where these variables were included, there was evidence that experiencing symptoms perceived to be consistent with HIV and prompts to test were associated with increased current HIV-risk perception. These findings are consistent with the Common-Sense Model (CSM) of illness representation and self-regulation. Methodological quality criteria were rarely met for the included studies. In addition, it was often difficult to ascertain whether potentially includable studies were eligible due to imprecise definitions of HIV-risk perception. Research and practice implications are discussed, with particular emphasis on the role of risk appraisals as a potential mediator of the relationship between HIV-risk behaviour, symptoms and current HIV-risk perception. PMID- 26852668 TI - Pattern formations and optimal packing. AB - Patterns of different symmetries may arise after solution to reaction-diffusion equations. Hexagonal arrays, layers and their perturbations are observed in different models after numerical solution to the corresponding initial-boundary value problems. We demonstrate an intimate connection between pattern formations and optimal random packing on the plane. The main study is based on the following two points. First, the diffusive flux in reaction-diffusion systems is approximated by piecewise linear functions in the framework of structural approximations. This leads to a discrete network approximation of the considered continuous problem. Second, the discrete energy minimization yields optimal random packing of the domains (disks) in the representative cell. Therefore, the general problem of pattern formations based on the reaction-diffusion equations is reduced to the geometric problem of random packing. It is demonstrated that all random packings can be divided onto classes associated with classes of isomorphic graphs obtained from the Delaunay triangulation. The unique optimal solution is constructed in each class of the random packings. If the number of disks per representative cell is finite, the number of classes of isomorphic graphs, hence, the number of optimal packings is also finite. PMID- 26852669 TI - Spatial synchrony in population dynamics: The effects of demographic stochasticity and density regulation with a spatial scale. AB - We generalize a previous simple result by Lande et al. (1999) on how spatial autocorrelated noise, dispersal rate and distance as well as strength of density regulation determine the spatial scale of synchrony in population density. It is shown how demographic noise can be incorporated, what effect it has on variance and spatial scale of synchrony, and how it interacts with the point process for locations of individuals under random sampling. Although the effect of demographic noise is a rather complex interaction with environmental noise, migration and density regulation, its effect on population fluctuations and scale of synchrony can be presented in a transparent way. This is achieved by defining a characteristic area dependent on demographic and environmental variances as well as population density, and subsequently using this area to define a spatial demographic coefficient. The demographic noise acts through this coefficient on the spatial synchrony, which may increase or decrease with increasing demographic noise depending on other parameters. A second generalization yields the modeling of density regulation taking into account that regulation at a given location does not only depend on the density at that site but also on densities in the whole territory or home range of individuals. It is shown that such density regulation with a spatial scale reduces the scale of synchrony in population fluctuations relative to the simpler model with density regulation at each location determined only by the local point density, and may even generate negative spatial autocorrelations. PMID- 26852666 TI - Glucosamine induces REDD1 to suppress insulin action in retinal Muller cells. AB - Resistance to insulin action is a key cause of diabetic complications, yet much remains unknown about the molecular mechanisms that contribute to the defect. Glucose-induced insulin resistance in peripheral tissues such as the retina is mediated in part by the hexosamine biosynthetic pathway (HBP). Glucosamine (GAM), a leading dietary supplement marketed to relieve the discomfort of osteoarthritis, is metabolized by the HBP, and in doing so bypasses the rate limiting enzyme of the pathway. Thus, exogenous GAM consumption potentially exacerbates the resistance to insulin action observed with diabetes-induced hyperglycemia. In the present study, we evaluated the effect of GAM on insulin action in retinal Muller cells in culture. Addition of GAM to Muller cell culture repressed insulin-induced activation of the Akt/mTORC1 signaling pathway. However, the effect was not recapitulated by chemical inhibition to promote protein O-GlcNAcylation, nor was blockade of O-GlcNAcylation sufficient to prevent the effects of GAM. Instead, GAM induced ER stress and subsequent expression of the protein Regulated in DNA Damage and Development (REDD1), which was necessary for GAM to repress insulin-stimulated phosphorylation of Akt on Thr308. Overall, the findings support a model whereby GAM promotes ER stress in retinal Muller cells, resulting in elevated REDD1 expression and thus resistance to insulin action. PMID- 26852670 TI - Iron Pyrite/Titanium Dioxide Photoanode for Extended Near Infrared Light Harvesting in a Photoelectrochemical Cell. AB - The design of active and stable semiconducting composites with enhanced photoresponse from visible light to near infrared (NIR) is a key to improve solar energy harvesting for photolysis of water in photoelectrochemical cell. In this study, we prepared earth abundant semiconducting composites consisting of iron pyrite and Titanium oxide as a photoanode (FeS2/TiO2 photoanode) for photoelectrochemical applications. The detailed structure and atomic compositions of FeS2/TiO2 photoanode was characterized by high-resolution transmission electron microscopy (HRTEM), energy-dispersive X-ray spectroscopy (EDS), powder X ray diffraction (XRD), inductively coupled plasma with atomic emission spectroscopy (ICPAES) and Raman spectroscopy. Through the proper sulfurization treatment, the FeS2/TiO2 photoanode exhibited high photoresponse from visible light extended to near infrared range (900 nm) as well as stable durability test for 4 hours. We found that the critical factors to enhance the photoresponse are on the elimination of surface defect of FeS2 and on the enhancement of interface charge transfer between FeS2 and TiO2. Our overall results open a route for the design of sulfur-based binary compounds for photoelectrochemical applications. PMID- 26852671 TI - Bacterial flora and the epidemiology of staphylococcus aureus in the nose among patients with symptomatic nasal septal perforations. AB - Conclusions Patients with symptomatic perforations of the nasal septum had a high prevalence of S. aureus in the nasal mucosa. Pulsed field gel electrophoresis (PFGE) analysis revealed a high genetic heterogeneity of S. aureus among both patients and controls. This indicates that presence of different strains of S. aureus can maintain a chronic inflammation in symptomatic nasal septal perforations. Objective The purpose of this study was to investigate the microbial flora around nasal septal perforations in patients having severe symptoms regarding bleeding, obstruction, and crustation associated with their perforation. Methods Twenty-five patients with untreated symptomatic nasal septal perforations were included. For culture, swabs around the perforations were collected. Bacteria were identified with standard laboratory techniques including a MALDI-TOF mass spectrometer. Epidemiological analysis was done using PFGE protocols. Bacteriological data were compared with data from a healthy control group. Results Staphylococcus aureus was present in the mucosa surrounding the nasal perforation significantly more often (p < 0.0001) in the patients (88%) compared to a control group (13%). Corynebacterium spp. and Propionibacterium spp. were significantly more frequently identified in the control group. The PFGE analysis of S. aureus strains revealed a high genetic heterogeneity and no specific S. aureus genotypes were associated with septal perforation. PMID- 26852673 TI - Multi-tissue transcriptomics for construction of a comprehensive gene resource for the terrestrial snail Theba pisana. AB - The land snail Theba pisana is native to the Mediterranean region but has become one of the most abundant invasive species worldwide. Here, we present three transcriptomes of this agriculture pest derived from three tissues: the central nervous system, hepatopancreas (digestive gland), and foot muscle. Sequencing of the three tissues produced 339,479,092 high quality reads and a global de novo assembly generated a total of 250,848 unique transcripts (unigenes). BLAST analysis mapped 52,590 unigenes to NCBI non-redundant protein databases and further functional analysis annotated 21,849 unigenes with gene ontology. We report that T. pisana transcripts have representatives in all functional classes and a comparison of differentially expressed transcripts amongst all three tissues demonstrates enormous differences in their potential metabolic activities. The genes differentially expressed include those with sequence similarity to those genes associated with multiple bacterial diseases and neurological diseases. To provide a valuable resource that will assist functional genomics study, we have implemented a user-friendly web interface, ThebaDB (http://thebadb.bioinfo-minzhao.org/). This online database allows for complex text queries, sequence searches, and data browsing by enriched functional terms and KEGG mapping. PMID- 26852674 TI - An Improved Neutral a-Glucosidase Assay for Assessment of Epididymal Function Validation and Comparison to the WHO Method. AB - Neutral a-glucosidase (NAG) activity in human seminal plasma is an important indicator for epididymis functionality. In the present study, the classic World Health Organization (WHO) method has been adapted to enhance assay robustness. Changes include modified enzyme reaction buffer composition and usage of an alternative enzyme inhibitor for background correction (glucose instead of castanospermine). Both methods have been tested in parallel on 144 semen samples, obtained from 94 patients/donors and 50 vasectomized men (negative control), respectively. Passing-Bablok regression analysis demonstrated equal assay performance. In terms of assay validation, analytical specificity, detection limit, measuring range, precision, and cut-off values have been calculated. These data confirm that the adapted method is a reliable, improved tool for NAG analysis in human semen. PMID- 26852675 TI - Development of a Hybrid Nanoprobe for Triple-Modality MR/SPECT/Optical Fluorescence Imaging. AB - Hybrid clinical imaging is an emerging technology, which improves disease diagnosis by combining already existing technologies. With the combination of high-resolution morphological imaging, i.e., MRI/CT, and high-sensitive molecular detection offered by SPECT/PET/Optical, physicians can detect disease progression at an early stage and design patient-specific treatments. To fully exploit the possibilities of hybrid imaging a hybrid probe compatible with each imaging technology is required. Here, we present a hybrid nanoprobe for triple modality MR/SPECT/Fluorescence imaging. Our imaging agent is comprised of superparamagnetic iron oxide nanoparticles (SPIONs), labeled with (99m)Tc and an Alexa fluorophore (AF), together forming (99m)Tc-AF-SPIONs. The agent was stable in human serum, and, after subcutaneous injection in the hind paw of Wistar rats, showed to be highly specific by accumulating in the sentinel lymph node. All three modalities clearly visualized the imaging agent. Our results show that a single imaging agent can be used for hybrid imaging. The use of a single hybrid contrast agent permits simultaneous hybrid imaging and, more conventionally, allow for single modality imaging at different time points. For example, a hybrid contrast agent enables pre-operative planning, intra-operative guidance, and post operative evaluation with the same contrast agent. PMID- 26852677 TI - Development of a Cancer Treatment with the Concomitant Use of Low-Intensity Ultrasound: Entering the Age of Simultaneous Diagnosis and Treatment. AB - In recent years, studies using ultrasound energy for cancer treatment have advanced, thus revealing the enhancement of drug effects by employing low intensity ultrasound. Furthermore, anti-angiogenesis against tumors is now attracting attention as a new cancer treatment. Therefore, we focused on the biological effects and the enhancement of drug effects brought by this low intensity ultrasound energy and reported on the efficacy against a uterine sarcoma model, by implementing the basic studies, for the first time, including the concomitant use of low-intensity ultrasound irradiation, as an expected new antiangiogenic therapy for cancer treatment. Furthermore, we have succeeded in simultaneously utilizing low-intensity ultrasound in both diagnosis and treatment, upon real time evaluation of the anti-tumor effects and anti angiogenesis effects using color Doppler ultrasound imaging. Although the biological effects of ultrasound have not yet been completely clarified, transient stomas were formed (Sonoporation) in cancer cells irradiated by low intensity ultrasound and it is believed that the penetration effect of drugs is enhanced due to the drug being more charged inside the cell through these stomas. Furthermore, it has become clear that the concomitant therapy of anti angiogenesis drugs and low-intensity ultrasound blocks the angiogenic factor VEGF produced by cancer cells, inhibits the induction of circulating endothelial progenitor cells in the bone marrow, and expedites angiogenic inhibitor TSP-1. Based on research achievements in recent years, we predict that the current diagnostic device for color Doppler ultrasound imaging will be improved in the near future, bringing with it the arrival of an age of "low-intensity ultrasound treatment that simultaneously enables diagnosis and treatment of cancer in real time." PMID- 26852676 TI - Trends in Nanomaterial-Based Non-Invasive Diabetes Sensing Technologies. AB - Blood glucose monitoring is considered the gold standard for diabetes diagnostics and self-monitoring. However, the underlying process is invasive and highly uncomfortable for patients. Furthermore, the process must be completed several times a day to successfully manage the disease, which greatly contributes to the massive need for non-invasive monitoring options. Human serums, such as saliva, sweat, breath, urine and tears, contain traces of glucose and are easily accessible. Therefore, they allow minimal to non-invasive glucose monitoring, making them attractive alternatives to blood measurements. Numerous developments regarding noninvasive glucose detection techniques have taken place over the years, but recently, they have gained recognition as viable alternatives, due to the advent of nanotechnology-based sensors. Such sensors are optimal for testing the amount of glucose in serums other than blood thanks to their enhanced sensitivity and selectivity ranges, in addition to their size and compatibility with electronic circuitry. These nanotechnology approaches are rapidly evolving, and new techniques are constantly emerging. Hence, this manuscript aims to review current and future nanomaterial-based technologies utilizing saliva, sweat, breath and tears as a diagnostic medium for diabetes monitoring. PMID- 26852679 TI - Endoscopic Color Doppler Ultrasonographic Evaluation of Gastric Varices Secondary to Left-Sided Portal Hypertension. AB - Gastric varices that arise secondary to the splenic vein occlusion can result in gastrointestinal hemorrhaging. Endoscopic color Doppler ultrasonography (ECDUS) was performed in 16 patients with gastric varices secondary to splenic vein occlusion. This study retrospectively evaluated the role of ECDUS in the diagnosis of gastric varices secondary to splenic vein occlusion. Thirteen patients had co-existing pancreatic diseases: 8 with chronic pancreatitis, 4 with cancer of the pancreatic body or tail and 1 with severe acute pancreatitis. Of the remaining 3 patients, 1 had myeloproliferative disease, 1 had advanced gastric cancer, and the third had splenic vein occlusion due to an obscure cause. The endoscopic findings of gastric varices were: variceal form (F) classified as enlarged tortuous (F2) in 12 cases and large, coil-shaped (F3) in 4 cases, and positive for erosion or red color sign of the variceal surface in 4 cases and negative in 12 cases. ECDUS color flow images of gastric variceal flow clearly depicted a round fundal region at the center, with varices expanding to the curvatura ventriculi major of the gastric body in all 16 cases. The velocities of F3 type gastric varices were significantly higher than those of the F2 type. The wall thickness of varices positive for erosion or red color sign was significantly less than the negative cases. I conclude that ECDUS color flow images of gastric variceal flow depicted specific findings of gastric varices secondary to splenic vein occlusion at the round fundal region at the center, with varices expanding to the curvatura ventriculi major of the gastric body. PMID- 26852681 TI - The Impact of Transient Hepatic Attenuation Differences in the Diagnosis of Pseudoaneurysm and Arteriovenous Fistula on Follow-Up CT Scans after Blunt Liver Trauma. AB - A feared complication to liver trauma is delayed vascular complication, such as pseudoaneurysm and arteriovenous fistula (PS/AF) seen as focal enhancement on contrast-enhanced computed tomography (CT) in the arterial phase. A hyperdense area termed transient hepatic attenuation difference (THAD) representing altered hepatic blood flow can be seen in the arterial phase near the liver lesion. The objective of this study was to describe THAD and PS/AF on follow-up CT after blunt liver trauma, and to evaluate if THAD influenced the evaluation of PS/AF. Three radiology residents retrospectively evaluated scans of 78 patients. The gold standard for PS/AF was an evaluation by an experienced senior radiologist, while THAD was a consensus between the residents. PS/AF was present in 14% and THAD in 54%. THAD was located in the periphery of the lesion with hazy borders and mean HU levels of 100, while PS/AF was located within the lesion with focal enhancement and mean HU levels of 170 (p < 0.05). In evaluation of PS/AF, the likelihood of agreement between the observers and the gold standard was 89% when THAD was present, and 98% when THAD was absent (p = 0.04). THAD is common and can hamper the evaluation of PS/AF. PMID- 26852678 TI - Endoscopic Optical Coherence Tomography for Clinical Gastroenterology. AB - Optical coherence tomography (OCT) is a real-time optical imaging technique that is similar in principle to ultrasonography, but employs light instead of sound waves and allows depth-resolved images with near-microscopic resolution. Endoscopic OCT allows the evaluation of broad-field and subsurface areas and can be used ancillary to standard endoscopy, narrow band imaging, chromoendoscopy, magnification endoscopy, and confocal endomicroscopy. This review article will provide an overview of the clinical utility of endoscopic OCT in the gastrointestinal tract and of recent achievements using state-of-the-art endoscopic 3D-OCT imaging systems. PMID- 26852680 TI - Commercial Smartphone-Based Devices and Smart Applications for Personalized Healthcare Monitoring and Management. AB - Smartphone-based devices and applications (SBDAs) with cost effectiveness and remote sensing are the most promising and effective means of delivering mobile healthcare (mHealthcare). Several SBDAs have been commercialized for the personalized monitoring and/or management of basic physiological parameters, such as blood pressure, weight, body analysis, pulse rate, electrocardiograph, blood glucose, blood glucose saturation, sleeping and physical activity. With advances in Bluetooth technology, software, cloud computing and remote sensing, SBDAs provide real-time on-site analysis and telemedicine opportunities in remote areas. This scenario is of utmost importance for developing countries, where the number of smartphone users is about 70% of 6.8 billion cell phone subscribers worldwide with limited access to basic healthcare service. The technology platform facilitates patient-doctor communication and the patients to effectively manage and keep track of their medical conditions. Besides tremendous healthcare cost savings, SBDAs are very critical for the monitoring and effective management of emerging epidemics and food contamination outbreaks. The next decade will witness pioneering advances and increasing applications of SBDAs in this exponentially growing field of mHealthcare. This article provides a critical review of commercial SBDAs that are being widely used for personalized healthcare monitoring and management. PMID- 26852682 TI - Spectro-FluorTM Technology for Reliable Detection of Proteins and Biomarkers of Disease: A Pioneered Research Study. AB - Quantitative and qualitative characterization of fluorinated molecules represents an important task. Fluorine-based medicinal chemistry is a fast-growing research area due to the positive impact of fluorine in drug discovery, and clinical and molecular imaging (e.g., magnetic resonance imaging, positron emission tomography). Common detection methods include fluorinated-based labelling using radioactive isotopes or fluorescent dyes. Nevertheless, these molecular imaging methods can be harmful for health due to the potential instability of fluorochromes and cytoxicity of radioisotopes. Therefore, these methods often require expensive precautionary measures. In this context, we have developed, validated and patented carbon-fluorine spectroscopy (CFSTM), recently renamed Spectro-FluorTM technology, which among a non-competitive family of in-house made devices called PLIRFATM (Pulsed Laser Isochronic Raman and Fluorescence ApparatusTM), allows reliable detection of Carbon-Fluorine (C-F) bonds. C-F bonds are known to be stable and safe labels once incorporated to any type of molecules, cells, compounds or (nano-) materials. In this pioneered research study, we used Spectro-FluorTM to assess biomarkers. As a proof-of-principle experiment, we have established a three-step protocol intended to rapid protein detection, which simply consisted of: (i) incorporating a sufficient concentration of an aromatic amino-acid (fluorinated versus non-fluorinated) into cultured cells; (ii) simultaneously isolating the fluorinated protein of interest and the non-fluorinated form of the protein (control) by immune-precipitation; (iii) comparatively analyzing the respective spectrum obtained for the two protein forms by Spectro-FluorTM. Thereby, we were able to differentiate, from colon cancer cells HCT-116, the fluorinated and non-fluorinated forms of p21, a key transcriptional factor and downstream target of p53, the so-called "guardian of the genome". Taken together, our data again demonstrates the beneficial alternative use of Spectro-FluorTM, which once combined with an innovative methodology permits one to quickly, reliably, safely and cost-effectively detect physiological or pathological proteins in cells. PMID- 26852683 TI - Current Challenges Towards the Development of a Blood Test for Parkinson's Disease. AB - Parkinson' disease (PD) is the second most prevalent neurodegenerative disease worldwide. To date, there is no disease-modifying agent, and current medical treatment only provides symptomatic benefits. Early diagnosis of PD would be useful in clinical practice to identify patients for clinical trials, test potential drugs and neuroprotective agents and track their therapeutic effect. Considerable progress has been made in the discovery and validation of diagnostic biomarkers for PD. In particular, blood-based biomarkers have shown promise in identifying PD patients in samples from independent clinical trials. Evaluation of these biomarkers in de novo patients and individuals at risk for PD remains a top priority. Here, we review the current advances and challenges toward the clinical translation of these biomarkers into a blood-based test for PD. PMID- 26852684 TI - Screen Printed Carbon Electrode Based Electrochemical Immunosensor for the Detection of Dengue NS1 Antigen. AB - An electrochemical immunosensor modified with the streptavidin/biotin system on screen printed carbon electrodes (SPCEs) for the detection of the dengue NS1 antigen was developed in this study. Monoclonal anti-NS1 capture antibody was immobilized on streptavidin-modified SPCEs to increase the sensitivity of the assay. Subsequently, a direct sandwich enzyme linked immunosorbent assay (ELISA) format was developed and optimized. An anti-NS1 detection antibody conjugated with horseradish peroxidase enzyme (HRP) and 3,3,5,5'-tetramethybezidine dihydrochloride (TMB/H2O2) was used as an enzyme mediator. Electrochemical detection was conducted using the chronoamperometric technique, and electrochemical responses were generated at -200 mV reduction potential. The calibration curve of the immunosensor showed a linear response between 0.5 ug/mL and 2 ug/mL and a detection limit of 0.03 ug/mL. Incorporation of a streptavidin/biotin system resulted in a well-oriented antibody immobilization of the capture antibody and consequently enhanced the sensitivity of the assay. In conclusion, this immunosensor is a promising technology for the rapid and convenient detection of acute dengue infection in real serum samples. PMID- 26852685 TI - Ionic polarization-induced current-voltage hysteresis in CH3NH3PbX3 perovskite solar cells. AB - CH3NH3PbX3 (MAPbX3) perovskites have attracted considerable attention as absorber materials for solar light harvesting, reaching solar to power conversion efficiencies above 20%. In spite of the rapid evolution of the efficiencies, the understanding of basic properties of these semiconductors is still ongoing. One phenomenon with so far unclear origin is the so-called hysteresis in the current voltage characteristics of these solar cells. Here we investigate the origin of this phenomenon with a combined experimental and computational approach. Experimentally the activation energy for the hysteretic process is determined and compared with the computational results. First-principles simulations show that the timescale for MA(+) rotation excludes a MA-related ferroelectric effect as possible origin for the observed hysteresis. On the other hand, the computationally determined activation energies for halide ion (vacancy) migration are in excellent agreement with the experimentally determined values, suggesting that the migration of this species causes the observed hysteretic behaviour of these solar cells. PMID- 26852686 TI - Multiple pathways regulate Cten in colorectal cancer without a Tensin switch. AB - CTEN/TNS4 is a member of the Tensin gene family. It localizes to focal adhesions and induces cell motility. The mechanisms regulating Cten expression are unclear although we have shown regulation by Kras in the colon and pancreas. In normal mammary cell lines, it is reportedly upregulated by epidermal growth factor receptor (EGFR) and STAT3 signalling and upregulation is accompanied by downregulation of Tensin 3 (Tensin switch). In this study, we investigated the roles of EGFR and STAT3 signalling in the regulation of Cten in colorectal cancer (CRC). In addition, we investigated calpain--a regulator of focal adhesion associated proteins whose relevance to Cten has not been investigated. CRC cell lines were stimulated with epidermal growth factor (EGF). This resulted in an increase in Cten and Tensin 3 protein. Kras was knocked down and this resulted in downregulation of Cten and Tensin 3. We next investigated the role of STAT3 signalling. Activation and knockdown of STAT3 resulted in downregulation and upregulation, respectively, of Cten. Inhibition of calpain resulted in upregulation of both Cten and Tensin 3. As the regulators of Cten also seemed to regulate Tensin 3, we tested the interaction between Cten and Tensin 3. Cten was forcibly expressed or knocked down resulting, respectively, in upregulation and downregulation of Tensin 3. We conclude that in CRC, Cten is upregulated by EGFR and Kras but downregulated by STAT3. We show that calpain may be a negative regulator of Cten and that a Tensin switch does not occur and, if anything, Cten stabilizes Tensin 3. PMID- 26852688 TI - Recombinant human brain natriuretic peptide attenuates trauma-/haemorrhagic shock induced acute lung injury through inhibiting oxidative stress and the NF-kappaB dependent inflammatory/MMP-9 pathway. AB - Acute lung injury (ALI) is one of the most serious complications in traumatic patients and is an important part of multiple organ dysfunction syndrome (MODS). Recombinant human brain natriuretic peptide (rhBNP) is a peptide with a wide range of biological activity. In this study, we investigated local changes in oxidative stress and the NF-kappaB-dependent matrix metalloproteinase-9 (MMP-9) pathway in rats with trauma/haemorrhagic shock (TH/S)-induced ALI and evaluated the effects of pretreatment with rhBNP. Forty-eight rats were randomly divided into four groups: sham operation group, model group, low-dosage rhBNP group and high-dosage rhBNP group (n = 12 for each group). Oxidative stress and MPO activity were measured by ELISA kits. MMP-9 activity was detected by zymography analysis. NF-kappaB activity was determined using Western blot assay. With rhBNP pretreatment, TH/S-induced protein leakage, increased MPO activity, lipid peroxidation and metalloproteinase (MMP)-9 activity were inhibited. Activation of antioxidative enzymes was reversed. The phosphorylation of NF-kappaB and the degradation of its inhibitor IkappaB were suppressed. The results suggested that the protection mechanism of rhBNP is possibly mediated through upregulation of anti-oxidative enzymes and inhibition of NF-kappaB activation. More studies are needed to further evaluate whether rhBNP is a suitable candidate as an effective inhaling drug to reduce the incidence of TH/S-induced ALI. PMID- 26852689 TI - Characterization of lesion formation in marmosets following inhalational challenge with different strains of Burkholderia pseudomallei. AB - The marmoset model of melioidosis was used to explore whether there was any difference in the disease presentation and/or the lesion formation following inhalational challenge with one of four strains of Burkholderia pseudomallei (K96243, 1026b, HBPUB10303a and HBPUB10134a). Marmosets were challenged with a range of bacterial doses and bacterial load, histological and physiological features were determined temporally following lethal disease. Melioidosis presented as an acute, febrile disease with bacteraemia, bacterial dissemination, necrotizing hepatitis, splenitis and pneumonia which was independent of the challenge strain. Generally, there were no major differences in the manifestation of melioidosis following challenge by the different strains of B. pseudomallei; however, there were some differences in the time to death and the severity of the pathological features. The pathological features observed in the liver and spleen of animals challenged with B. pseudomallei strain 1026b were statistically less severe (P < 0.05) and less frequent. However, more severe foci of disease were evident in the lungs of animals challenged with strain 1026b. In all cases, the lesions developed from small areas of bacteria-infected macrophages surrounded by non-infected neutrophils into large lesions with both immune cell types infected. The marmoset model was a useful tool enabling the distinction of subtle difference in the pathological response to B. pseudomallei. PMID- 26852690 TI - miR-1, regulated by LMP1, suppresses tumour growth and metastasis by targeting K ras in nasopharyngeal carcinoma. AB - There is evidence to show that downregulation of miR-1 expression is closely related to cancer progression, including in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms underlying miR-1 downregulation in NPC remain largely unknown, especially its association with Epstein-Barr virus (EBV). In this study we found that restoration of miR-1 dramatically inhibited cell invasion in vitro, together with tumour growth and metastasis in vivo. Importantly, we found that LMP1, an Epstein-Barr virus (EBV)-associated protein, suppressed miR-1 expression. Furthermore, we identified K-ras as a novel direct target of miR-1. Our results demonstrated for the first time that miR-1 was suppressed by LMP1 and its tumour-suppressive effects were mediated chiefly by repressing K-ras expression. We propose that miR-1 could serve as an independent biomarker to identify patients with different clinical characteristics. PMID- 26852687 TI - Amomum tsao-ko fruit extract suppresses lipopolysaccharide-induced inducible nitric oxide synthase by inducing heme oxygenase-1 in macrophages and in septic mice. AB - Amomum tsao-ko Crevost et Lemarie (Zingiberaceae) has traditionally been used to treat inflammatory and infectious diseases, such as throat infections, malaria, abdominal pain and diarrhoea. This study was designed to assess the anti inflammatory effects and the molecular mechanisms of the methanol extract of A. tsao-ko (AOM) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages and in a murine model of sepsis. In LPS-induced RAW 264.7 macrophages, AOM reduced the production of nitric oxide (NO) by inhibiting inducible nitric oxide synthase (iNOS) expression, and increased heme oxygenase-1 (HO-1) expression at the protein and mRNA levels. Pretreatment with SnPP (a selective inhibitor of HO-1) and silencing HO-1 using siRNA prevented the AOM-mediated inhibition of NO production and iNOS expression. Furthermore, AOM increased the expression and nuclear accumulation of NF-E2-related factor 2 (Nrf2), which enhanced Nrf2 binding to antioxidant response element (ARE). In addition, AOM induced the phosphorylation of extracellular regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) and generated reactive oxygen species (ROS). Furthermore, pretreatment with N-acetyl-l-cysteine (NAC; a ROS scavenger) diminished the AOM induced phosphorylation of ERK and JNK and AOM-induced HO-1 expression, suggesting that ERK and JNK are downstream mediators of ROS during the AOM induced signalling of HO-1 expression. In LPS-induced endotoxaemic mice, pretreatment with AOM reduced NO serum levels and liver iNOS expression and increased HO-1 expression and survival rates. These results indicate that AOM strongly inhibits LPS-induced NO production by activating the ROS/MAPKs/Nrf2 mediated HO-1 signalling pathway, and supports its pharmacological effects on inflammatory diseases. PMID- 26852693 TI - Passing on the medicinal chemistry baton: training undergraduates to be industry ready through research projects between the University of Nottingham and GlaxoSmithKline. AB - In this article we describe a radically different industry-academia collaboration between the School of Chemistry, University of Nottingham, and GlaxoSmithKline (GSK), aiming to train students in research and give them an insight into medicinal chemistry as practiced in industry. The project concerns the discovery of potent and selective alphavbeta6 integrin antagonists to treat idiopathic pulmonary fibrosis; the synthetic chemistry is performed by a group of ten final year undergraduates and the biological and physicochemical screening data are generated by GSK. The project planning, organisation and operation are discussed, together with some of the challenges and rewards of working with undergraduates. PMID- 26852694 TI - Combining phage display with de novo protein sequencing for reverse engineering of monoclonal antibodies. AB - The enormous diversity created by gene recombination and somatic hypermutation makes de novo protein sequencing of monoclonal antibodies a uniquely challenging problem. Modern mass spectrometry-based sequencing will rarely, if ever, provide a single unambiguous sequence for the variable domains. A more likely outcome is computation of an ensemble of highly similar sequences that can satisfy the experimental data. This outcome can result in the need for empirical testing of many candidate sequences, sometimes iteratively, to identity one which can replicate the activity of the parental antibody. Here we describe an improved approach to antibody protein sequencing by using phage display technology to generate a combinatorial library of sequences that satisfy the mass spectrometry data, and selecting for functional candidates that bind antigen. This approach was used to reverse engineer 2 commercially-obtained monoclonal antibodies against murine CD137. Proteomic data enabled us to assign the majority of the variable domain sequences, with the exception of 3-5% of the sequence located within or adjacent to complementarity-determining regions. To efficiently resolve the sequence in these regions, small phage-displayed libraries were generated and subjected to antigen binding selection. Following enrichment of antigen-binding clones, 2 clones were selected for each antibody and recombinantly expressed as antigen-binding fragments (Fabs). In both cases, the reverse-engineered Fabs exhibited identical antigen binding affinity, within error, as Fabs produced from the commercial IgGs. This combination of proteomic and protein engineering techniques provides a useful approach to simplifying the technically challenging process of reverse engineering monoclonal antibodies from protein material. PMID- 26852691 TI - Treatment with Mesna and n-3 polyunsaturated fatty acids ameliorates experimental ulcerative colitis in rats. AB - Oxidative damage is a central feature of ulcerative colitis. Here, we tested whether the antioxidant Mesna, when administered alone or in combination with n-3 polyunsaturated fatty acids (n-3 PUFAs), affects the outcome of dextran sodium sulphate (DSS)-induced ulcerative colitis in rats. After the induction of colitis, DSS-treated rats were further treated orally (p.o), intraperitoneally (i.p) or intrarectally (i.r) for either 7 or 14 days with Mesna, n-3 PUFAs or both. Rats were euthanized at the end of each treatment period. Clinical disease activity index was recorded throughout the experiment. At necropsy colorectal gross lesions were scored. Colitis was scored histologically, and the expression of myeloperoxidase (MPO), caspase-3, inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-kappaBeta) in colonic tissue was assessed by immunohistochemistry. Mesna alone was sufficient to significantly reduce colorectal tissue damage when administered orally or intraperitoneally. Orally coadministered n-3 PUFAs enhanced this effect, resulting in the significant suppression of DSS colitis after 7 days, and a remarkable recovery of colorectal mucosa was evident after 14 days of treatment. The amelioration of colon pathology co-existed with a significant decrease in MPO expression, overexpression of iNOS and reduction of nuclear NF-kappaB p65 in inflammatory cells, and the suppression of apoptosis in colonic epithelial cells. The simultaneous administration of Mesna and n-3 PUFAs is particularly effective in ameliorating DSS colitis in rats, by reducing oxidative stress, inflammation and apoptosis, probably through a mechanism that involves the inhibition of NF-kappaB and overexpression of iNOS. PMID- 26852695 TI - Utility of fetal MRI for workup of fetal central nervous system anomalies in an Australian maternal-fetal medicine cohort. AB - OBJECTIVES: To evaluate how fetal MRI is influencing current clinical practice and outcomes for central nervous system (CNS) anomalies in the Australian maternal-fetal medicine (MFM) setting. MATERIAL AND METHODS: Retrospective audit of cases January 2008-August 2013 referred for MFM ultrasound and MRI for suspected fetal CNS anomaly. Demographics, referral information, initial MFM diagnoses and investigations, MRI diagnoses, subsequent pregnancy management and perinatal outcome were examined. RESULTS: Fifty-seven women (41 singleton, 16 twin pregnancies) were seen at mean gestation of 23.7 +/- 6.5 weeks. Major referral indications included ventriculomegaly (VM, 39%) and posterior fossa anomaly (PFA, 18%). MRI was performed at mean 27.2 +/- 5.3 weeks. Diagnosis was altered from ultrasound in 31/57 cases (54%); 14 improving and 17 worsening prognosis. MRI findings worsening prognosis were more significant VM and PFA, agenesis of the corpus callosum, neuronal migration disorders and intraventricular haemorrhage. TOP or selective reduction occurred in 11 of 57 cases after full clinical workup (six where MRI worsened prognosis, five where MRI confirmed US poor prognosis). Mean gestation at birth was 37.2 +/- 4.1 weeks for continuing pregnancies. There were nine cases of additional postnatal diagnoses, including four CNS anomalies. After neonatal workup, physical and/or developmental delay was anticipated for at least 14 of 43 (33%) infants. CONCLUSIONS: MRI added significant diagnostic information in about half the cases referred for workup of suspected CNS anomaly. In six of 17 cases where MRI worsened prognosis, TOP was chosen. Both additional CNS and non-CNS anomalies were diagnosed postnatally in 20%, emphasising the uncertain prognosis for, and evolution of, suspected CNS anomaly in fetuses. PMID- 26852696 TI - Properties, theoretical study and crystal structure of 3-benzothiazole-9-ethyl carbazole. AB - The title compound of 3-benzothiazole-9-ethyl carbazole was synthesized by the reaction of 3-aldehyde-9-ethyl carbazole and 2-aminothiophenol. The compound was characterized by (1) H nuclear magnetic resonance (NMR) and mass spectrometry (MS). Its crystal structure was obtained and determined by single crystal X-ray diffraction. The results showed that the crystal belongs to the orthorhombic crystal system and the cell parameters of space group P2(1)2(1)2(1) were a = 5.6626 (12) A, b = 12.606 (3) A, c = 22.639 (5) A, alpha = 90 degrees , beta = 90 degrees , gamma = 90 degrees , V = 1616.0 (6) A(3) , Z = 4, Dc = 1.350 mg/m(3) . The UV-vis and fluorescence spectra were also studied preliminarily. The fluorescence spectra of the title compound with bovine serum albumin (BSA) showed that BSA could be marked with the compound and the stability constant between them was 0.82 * 10(7) M(-1) . Meanwhile, the crystal and molecule were theoretically surveyed by density functional tight-binding (DFTB). The results showed that there was an orbital overlap for lowest unoccupied molecular orbital (LUMO) between the neighbouring molecules for the crystal, which is different from the molecule structure. It was also showed that the crystal structure is a non-conductor. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26852697 TI - Venous aneurysm developed in duplicated inferior vena cava: MDCT features. PMID- 26852698 TI - The complete mitochondrial genome of Anopheles minimus (Diptera: Culicidae) and the phylogenetics of known Anopheles mitogenomes. AB - Anopheles minimus is an important vector of human malaria in southern China and Southeast Asia. The phylogenetics of mosquitoes has not been well resolved, and the mitochondrial genome (mtgenome) has proven to be an important marker in the study of evolutionary biology. In this study, the complete mtgenome of An. minimus was sequenced for the first time. It is 15 395 bp long and encodes 37 genes, including 13 protein-coding genes (PCGs), 22 transfer RNAs (tRNAs), two ribosomal RNAs (rRNAs) and a non-coding region. The gene organization is consistent with those of known Anopheles mtgenomes. The mtgenome performs a clear bias in nucleotide composition with a positive AT-skew and a negative GC-skew. All 13 PCGs prefer to use the codon UUA (Leu), ATN as initiation codon but cytochrome-oxidase subunit 1 (COI) and ND5, with TCG and GTG, and TAA as termination codon, but COI, COII, COIII and ND4, all with the incomplete T. tRNAs have the typical clover-leaf structure, but tRNA(Ser(AGN)) is consistent with known Anopheles mtgenomes. The control region includes a conserved T-stretch and a (TA)n stretch, and has the highest A+T content at 93.1%. The phylogenetics of An. minimus with 18 other Anopheles species was constructed by maximum likelihood and Bayesian inference, based on concatenated PCG sequences. The subgenera, Cellia and Anopheles, and Nyssorhynchus and Kerteszia have mutually close relationships, respectively. The Punctulatus group and Leucosphyrus group of Neomyzomyia Series, and the Albitarsis group of Albitarsis Series were suggested to be monophyletic. The monophyletic status of the subgenera, Cellia, Anopheles, Nyssorhynchus and Kerteszia need to be further elucidated. PMID- 26852699 TI - Research that adds something.... PMID- 26852700 TI - Place matters. PMID- 26852701 TI - 17beta-Estradiol/N-acetylcysteine interaction enhances the neuroprotective effect on dopaminergic neurons in the weaver model of dopamine deficiency. AB - The weaver mouse, is a phenocopy of Parkinson's disease (PD) in which dopaminergic neurons degenerate gradually during development, reaching at P21 a neurodegeneration of 55%. Thus, the weaver mouse constitutes an appropriate in vivo PD model for investigating the effect of neuroprotective agents. In the present study, long-term treatment (from P1 to P21) with 17beta-estradiol (17beta estradiol) significantly protected the dopaminergic neurons in the substantia nigra (SN) of weaver mouse by 54%, as was detected by immunohistochemical experiments, using the specific antibody against tyrosine hydroxylase (TH). This dopaminergic neuroprotection is in line with our biochemical results showing that 17beta-estradiol treatment significantly decreased the high lipid peroxidation levels seen in the SN of weaver mouse, indicating high oxidative stress. Interestingly, co-administration of 17beta-estradiol with N-acetylcysteine (NAC, precursor molecule of glutathione (GSH)) further significantly increased the survival of dopaminergic neurons in the SN (by 85%), with a parallel further decrease of lipid peroxidation to normal levels. Our results show the in vivo neuroprotective effect of 17beta-estradiol, which is strongly enhanced by co administration of NAC, indicating a strong synergistic effect of the two drugs. Furthermore, the main mechanism underlying this neuroprotective action seems to be the reversal of the oxidative stress shown by the high peroxidation levels. These results could be of clinical relevance since both drugs are already used separately in the clinic, 17beta-estradiol for treatment of PD and NAC as a mucolytic agent and for the treatment of several disorders. PMID- 26852703 TI - Caffeine prevents LPS-induced inflammatory responses in RAW264.7 cells and zebrafish. AB - Caffeine is a white crystalline xanthine alkaloid found in the seeds of coffee plants and leaves of the tea bush. In this study, we evaluated whether caffeine exerts anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation both in vitro and in vivo. RAW264.7 cells were treated with various concentrations of caffeine in the presence or absence of LPS. Caffeine decreased the LPS-induced inflammatory mediator, nitric oxide (NO). Caffeine treatment also reduced the expression of pro-inflammatory genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-3, IL-6 and IL 12, and decreased both IL-6 secretion and phosphorylated p38MAPK expression in LPS-treated RAW264.7 cells. Caffeine inhibited nuclear translocation of nuclear factor kappaB (NF-kappaB) via IkappaBalpha phosphorylation. In addition, caffeine inhibited LPS-induced NO production in zebrafish. These results suggest that caffeine may suppress LPS-induced inflammatory responses in RAW264.7 cells by regulating NF-kappaB activation and MAPK phosphorylation. PMID- 26852702 TI - Transplantation of neural progenitor cells in chronic spinal cord injury. AB - Previous studies demonstrated that neural progenitor cells (NPCs) transplanted into a subacute contusion injury improve motor, sensory, and bladder function. In this study we tested whether transplanted NPCs can also improve functional recovery after chronic spinal cord injury (SCI) alone or in combination with the reduction of glial scar and neurotrophic support. Adult rats received a T10 moderate contusion. Thirteen weeks after the injury they were divided into four groups and received either: 1. Medium (control), 2. NPC transplants, 3. NPC+lentivirus vector expressing chondroitinase, or 4. NPC+lentivirus vectors expressing chondroitinase and neurotrophic factors. During the 8 weeks post transplantation the animals were tested for functional recovery and eventually analyzed by anatomical and immunohistochemical assays. The behavioral tests for motor and sensory function were performed before and after injury, and weekly after transplantation, with some animals also tested for bladder function at the end of the experiment. Transplant survival in the chronic injury model was variable and showed NPCs at the injury site in 60% of the animals in all transplantation groups. The NPC transplants comprised less than 40% of the injury site, without significant anatomical or histological differences among the groups. All groups also showed similar patterns of functional deficits and recovery in the 12 weeks after injury and in the 8 weeks after transplantation using the Basso, Beattie, and Bresnahan rating score, the grid test, and the Von Frey test for mechanical allodynia. A notable exception was group 4 (NPC together with chondroitinase and neurotrophins), which showed a significant improvement in bladder function. This study underscores the therapeutic challenges facing transplantation strategies in a chronic SCI in which even the inclusion of treatments designed to reduce scarring and increase neurotrophic support produce only modest functional improvements. Further studies will have to identify the combination of acute and chronic interventions that will augment the survival and efficacy of neural cell transplants. PMID- 26852704 TI - An Engineered Rare Codon Device for Optimization of Metabolic Pathways. AB - Rare codons generally arrest translation due to rarity of their cognate tRNAs. This property of rare codons can be utilized to regulate protein expression. In this study, a linear relationship was found between expression levels of genes and copy numbers of rare codons inserted within them. Based on this discovery, we constructed a molecular device in Escherichia coli using the rare codon AGG, its cognate tRNA (tRNA(Arg) (CCU)), modified tRNA(Asp) (GUC -> CCU), and truncated aspartyl-tRNA synthetase (TDRS) to switch the expression of reporter genes on or off as well as to precisely regulate their expression to various intermediate levels. To underscore the applicability of our work, we used the rare codon device to alter the expression levels of four genes of the fatty acid synthesis II (FASII) pathway (i.e. fabZ, fabG, fabI, and tesA') in E. coli to optimize steady-state kinetics, which produced nearly two-fold increase in fatty acid yield. Thus, the proposed method has potential applications in regulating target protein expression at desired levels and optimizing metabolic pathways by precisely tuning in vivo molar ratio of relevant enzymes. PMID- 26852706 TI - Assessment of the Endoscopic Endonasal Transclival Approach for Surgical Clipping of Anterior Pontine Anterior-Inferior Cerebellar Artery Aneurysms. AB - OBJECTIVE: Aneurysms of the anterior pontine segment of the anterior-inferior cerebellar artery (AICA) are uncommon. Their treatment is challenging because critical neurovascular structures are adjacent to it and the available surgical corridors are narrow and deep. Although endoscopic endonasal approaches are accepted for treating midline skull base lesions, their role in the treatment vascular lesions remains undefined. The present study is aimed to assess the anatomic feasibility of the endoscopic endonasal transclival (EET) approach for treating anterior pontine AICA aneurysms and compare it with the subtemporal anterior transpetrosal (SAT) approach. METHODS: Twelve cadaveric specimens were prepared for surgical simulation. The AICAs were exposed using both EET and SAT approaches. Surgical window area and the length of the exposed artery were measured. The distance from the origin of the artery to the clip applied for proximal control was measured. The number of AICA perforators exposed and the anatomic features of each AICA were recorded. RESULTS: The EET approach provided a wider surgical window area compared with the SAT (P < 0.001). More AICA perforators were visualized using the EET approach (P < 0.05). To obtain proximal control of the AICA, an aneurysm clip could be applied closer to the origin of AICA using EET (0.2 +/- 0.42 mm) compared with SAT (6.26 +/- 3.4 mm) (P < 0.001). CONCLUSION: Clipping anterior pontine AICA aneurysms using the EET approach is feasible. Compared with SAT, the EET approach provides advantages in surgical window area, ensuring proximal control before aneurysm dissection, visualization of perforating branches, and better proximal control. PMID- 26852705 TI - The peroxisomal Lon protease LonP2 in aging and disease: functions and comparisons with mitochondrial Lon protease LonP1. AB - Peroxisomes are ubiquitous eukaryotic organelles with the primary role of breaking down very long- and branched-chain fatty acids for subsequent beta oxidation in the mitochondrion. Like mitochondria, peroxisomes are major sites for oxygen utilization and potential contributors to cellular oxidative stress. The accumulation of oxidatively damaged proteins, which often develop into inclusion bodies (of oxidized, aggregated, and cross-linked proteins) within both mitochondria and peroxisomes, results in loss of organelle function that may contribute to the aging process. Both organelles possess an isoform of the Lon protease that is responsible for degrading proteins damaged by oxidation. While the importance of mitochondrial Lon (LonP1) in relation to oxidative stress and aging has been established, little is known regarding the role of LonP2 and aging related changes in the peroxisome. Recently, peroxisome dysfunction has been associated with aging-related diseases indicating that peroxisome maintenance is a critical component of 'healthy aging'. Although mitochondria and peroxisomes are both needed for fatty acid metabolism, little work has focused on understanding the relationship between these two organelles including how age dependent changes in one organelle may be detrimental for the other. Herein, we summarize findings that establish proteolytic degradation of damaged proteins by the Lon protease as a vital mechanism to maintain protein homeostasis within the peroxisome. Due to the metabolic coordination between peroxisomes and mitochondria, understanding the role of Lon in the aging peroxisome may help to elucidate cellular causes for both peroxisome and mitochondrial dysfunction. PMID- 26852707 TI - Neurosurgical Defensive Medicine in Texas and Illinois: A Tale of 2 States. AB - OBJECTIVE: To compare the self-reported liability characteristics and defensive medicine practices of neurosurgeons in Texas with neurosurgeons in Illinois in an effort to describe the effect of medicolegal environment on defensive behavior. METHODS: An online survey was sent to 3344 members of the American Board of Neurological Surgery. Respondents were asked questions in 8 domains, and responses were compared between Illinois, the state with the highest reported average malpractice insurance premium, and Texas, a state with a relatively low average malpractice insurance premium. RESULTS: In Illinois, 85 of 146 (58.2%) neurosurgeons surveyed responded to the survey. In Texas, 65 of 265 (24.5%) neurosurgeons surveyed responded. In Illinois, neurosurgeons were more likely to rate the overall burden of liability insurance premiums to be an extreme/major burden (odds ratio [OR] = 7.398, P < 0.001) and to have >$2 million in total coverage (OR = 9.814, P < 0.001) than neurosurgeons from Texas. Annual malpractice insurance premiums in Illinois were more likely to be higher than $50,000 than in Texas (OR = 9.936, P < 0.001), and survey respondents from Illinois were more likely to believe that there is an ongoing medical liability crisis in the United States (OR = 9.505, P < 0.001). Neurosurgeons from Illinois were more likely to report that they very often/always order additional imaging (OR = 2.514, P = 0.011) or very often/always request additional consultations (OR = 2.385, P = 0.014) compared with neurosurgeons in Texas. CONCLUSIONS: Neurosurgeons in Illinois are more likely to believe that there is an ongoing medical liability crisis and more likely to practice defensively than neurosurgeons in Texas. PMID- 26852708 TI - Extensive Therapies for Extraneural Metastases from Glioblastoma, as Confirmed with the OncoScan Assay. AB - BACKGROUND: The diagnosis of extraneural metastasis from glioblastoma is usually based on the histopathology and immunohistochemical staining of a tumor specimen. Information regarding the molecular features of glioblastoma and optimal treatment strategies for extraneural metastasis is limited. CASE DESCRIPTION: A 58-year-old woman with a glioblastoma located in the left temporal lobe underwent resection followed by radiotherapy plus concomitant and adjuvant temozolomide. Ipsilateral cervical lymph node tumors were treated 29 months later with supraomohyoid neck dissection and temozolomide. The diagnosis of lymph node metastases from glioblastoma was confirmed with an OncoScan assay and pathologic analysis. The brain and lymph node tumors had identical genotypes: C228T-mutated TERT promoter, wild-type IDH1, wild-type IDH2, wild-type TP53, EGFR amplification, and unmethylated MGMT promoter. Subsequently, multiple bone metastases were detected and treated with CyberKnife radiosurgery. Widespread extraneural metastases were detected 49 months after the initial diagnosis, and the patient underwent chemotherapy with cisplatin and semustine. There was no evidence of intracranial relapse until death, which occurred 5 months after chemotherapy. CONCLUSIONS: Similar to carcinomas, glioblastomas can spread via the lymphatic route. Extensive therapies for extraneural metastases from glioblastoma can alleviate discomfort and prolong survival, especially in patients without intracranial relapse. PMID- 26852709 TI - Intramedullary Recurrence of a Thoracic Meningioma-Presentation of an Unusual Case and Review of the Literature. AB - BACKGROUND: Spinal meningiomas are typically extra-axial, slow-growing, benign tumors that arise from the arachnoid cap cells. Intramedullary spinal meningiomas are exceedingly rare with few cases reported in the literature. CASE DESCRIPTION: A 64-year-old man with a history of grade I thoracic meningioma at the T4 level resected initially in 1989 and who required reoperation in 2013 for intradural, extramedullary recurrence of tumor presented again in 2015 with gait difficulty. Magnetic resonance imaging revealed a soft tissue mass at the T3 to T4 levels on the left side of the canal that was mildly enhancing on T1 contrasted sequences. The patient was taken to the operating room, where a purely intramedullary recurrence was discovered without extramedullary extension or a dural-based attachment. The intramedullary tumor was completely resected, and postoperatively the patient recovered well and was at his neurologic baseline. The patient ultimately underwent proton beam radiotherapy because this tumor, although benign, had recurred twice. CONCLUSIONS: Intramedullary spinal meningiomas, particularly intramedullary low-grade recurrence of a previously extramedullary tumor, are rare phenomena. Although the pathogenic mechanisms are not well understood, intramedullary recurrence as described in this patient may reflect extrinsic factors related to prior surgical resections in addition to histologic progression. When operating on recurrent extramedullary lesions, aggressive arachnoid dissection may predispose patients to unusual patterns of recurrence. PMID- 26852710 TI - Neurosurgery and Telemedicine in the United States: Assessment of the Risks and Opportunities. AB - BACKGROUND: Telemedicine has seen substantial growth in the past 20 years, related to technologic advancements and evolving reimbursement policies. The risks and opportunities of neurosurgical telemedicine are nuanced. METHODS: We reviewed general and peer-reviewed literature as it relates to telemedicine and neurosurgery, with particular attention to best practices, relevant state and federal policy conditions, economic evaluations, and prospective clinical studies. RESULTS: Despite technologic development, growing interest, and increasing reimbursement opportunities, telemedicine's utilization remains limited because of concerns regarding an apparent lack of need for telemedicine services, lack of widespread reimbursement, lack of interstate licensure reciprocity, lack of universal access to necessary technology, concerns about maintaining patient confidentiality, and concerns and limited precedent regarding liability issues. The Veterans Health Administration, a component of the U.S. Department of Veterans Affairs, represents a setting in which these concerns can be largely obviated and is a model for telemedicine best practices. Results from the VA demonstrate substantial cost savings and patient satisfaction with remote care for chronic neurologic conditions. Overall, the economic and clinical benefits of telemedicine will likely come from 1) diminished travel times and lost work time for patients; 2) remote consultation of subspecialty experts, such as neurosurgeons; and 3) remote consultation to assist with triage and care in time-sensitive scenarios, including acute stroke care and "teletrauma." CONCLUSIONS: Telemedicine is effective in many health care scenarios and will become more relevant to neurosurgical patient care. We favor proceeding with legislation to reduce barriers to telemedicine's growth. PMID- 26852711 TI - Antibiotic Reservoir Injection Reduces Shunt Infection in Adults. AB - BACKGROUND: Shunt infections are a major complication following ventricular shunts in adults that lead to increased heath care costs, patient morbidity, and mortality. Methods to decrease shunt infection include antibiotic-impregnated catheters, protocol-based surgery, and shunt reservoir antibiotic injection. METHODS: An Institutional Review Board-approved retrospective review was performed for all adult shunt surgeries performed from January 2000 to September 2013 at a single academic institution. Records were cross-indexed with hospital billing records to identify patients who received antibiotic injections and cross referenced with a prospective infection control database of all surgical site infections. The primary outcome measure was shunt infection within 1 year of surgery. RESULTS: Five-hundred thirteen adult patients met inclusion criteria. Antibiotic reservoir injection was associated with a significantly lower rate of infection (2.6%) when compared with no injection (6.3%, P = 0.0455). The antibiotic injection group also included significantly more patients with infection risk factors than the control group (38.8% vs. 18.0%, P < 0.005). CONCLUSION: Antibiotic reservoir injection is an effective method of reducing shunt infections in adults when combined with standard infection control measures. PMID- 26852712 TI - Hemodynamic Effect of Flow Diverter and Coils in Treatment of Large and Giant Intracranial Aneurysms. AB - BACKGROUND: This study aimed to investigate the hemodynamic changes induced by a flow diverter (FD) and coils in the treatment of internal carotid artery aneurysms, as well as to evaluate the effect of this treatment by using angiographic follow-up data. METHODS: Six large and giant aneurysms were treated by the Tubridge FD and loose packing coils between June 2013 and May 2015. Patient-specific models were constructed and analyzed using a computational fluid dynamics (CFD) method. The virtual FD deployment method was used to implant the Tubridge stent into a 3-dimensional digital subtraction angiographic image of the aneurysms, and the coils were simulated by a porous medium model. RESULTS: Tubridge FD alone can significantly reduce the intra-aneurysmal flow velocity (0.17 +/- 0.05 m/s-0.11 +/- 0.06 m/s, P < 0.001) and wall shear stress (WSS, 1.39 +/- 0.29 Pa-0.77 +/- 0.34 Pa, P = 0.001) and increase the low wall shear area (LSA, 6.38% +/- 1.49%-34.60% +/- 28.90%, P = 0.047). Coils, as a supplementary measure, further reduced the velocity (0.11 +/- 0.06 m/s-0.08 +/- 0.05 m/s, P = 0.03) and WSS (0.77 +/- 0.34 Pa-0.47 +/- 0.35 Pa, P = 0.04) and increased the LSA (34.60% +/- 28.90%-63.33% +/- 34.82%, P = 0.044). Aneurysm with sustained strong inflow after treatment (case 3, 25% reduction in velocity, 12% reduction in WSS, and 16% increment in LSA) showed partial patency, whereas others with a weaker inflow jet (mean 56% reduction in velocity, 74% reduction in WSS, and 1081% increment in LSA) showed complete occlusion at follow-up. CONCLUSIONS: On the basis of using the CFD method, adjunctive coiling with the Tubridge FD placement may significantly reduce intra-aneurysmal flow velocity and WSS, promoting thrombosis formation and occlusion of aneurysms. PMID- 26852714 TI - Long-Term Results and Efficacy of Laminectomy with Fusion Versus Young Laminoplasty for the Treatment of Degenerative Spinal Stenosis. AB - OBJECTIVE: In the treatment of degenerative lumbar stenosis, facet-sparing laminectomy with instrumented fusion (FSL) was recently almost totally replaced by less invasive, allegedly equally effective surgical techniques. We performed a long-term comparison between outcomes after Young laminoplasty (YL) as a representative of the less invasive technique and FSL. METHODS: From December 4, 2000, to March 11, 2005, 56 patients with a history of neurogenic claudication and radiologically verified absolute lumbar stenosis were surgically treated. After applying inclusion and exclusion criteria, 44 patients were enrolled. RESULTS: Using the Oswestry Disability Index scale, significant improvement on 1 year and 8-year follow-up examinations was noticed in the FSL and YL groups. The Oswestry Disability Index was significantly better in the FSL group compared with the YL group at the 8-year follow-up (27.82 +/- 1.918 vs. 40.74 +/- 2.163). CONCLUSIONS: FSL is a more invasive and more expensive surgical technique than YL. In a short-term and long-term follow-up comparison, FSL is a more successful operative technique, and the difference increases over time in favor of FSL. PMID- 26852713 TI - Craniectomy Versus Craniotomy for Posterior Fossa Metastases: Complication Profile. AB - OBJECTIVE: Surgical resection of posterior fossa metastases (PFM) includes either suboccipital craniotomy or suboccipital craniectomy. The optimal surgical technique is yet to be defined. We examined the association between the chosen surgical approach and the occurrence of postoperative complications. METHODS: We retrospectively evaluated medical records and imaging characteristics of patients who underwent resection of newly diagnosed PFM between 2003 and 2014 in our medical center to identify covariates that significantly affected postoperative complications. RESULTS: Of 917 patients with brain metastases, 88 patients underwent surgery for PFM and were included in the study. Craniectomy was performed in 54 cases (61%). Urgent postoperative posterior fossa decompression or cerebrospinal fluid diversion was performed in 4 patients (4.5%). Postoperative complications included postoperative central nervous system infection (n = 10 [12%]), cerebrospinal fluid leak (n = 3 [4%]), wound dehiscence (n = 6 [7%]), and long-term pseudomeningocele (n = 12 [14%]). The perioperative mortality rate was 2.3% (n = 2). Multivariate analysis that included patient baseline characteristics, imaging study parameters, and surgical approaches demonstrated that suboccipital craniectomy was associated with more postoperative complications (P = 0.03, odds ratio = 4.48, 95% confidence interval = 1.14-17.6). There was no correlation between patient baseline characteristics or surgical technique with the need for urgent postoperative posterior fossa decompression or cerebrospinal fluid diversion. CONCLUSIONS: Suboccipital craniotomy may be associated with a lower incidence of postoperative morbidity compared with suboccipital craniectomy and should be considered as the preferred approach for the resection of PFM. PMID- 26852715 TI - Insights into the Cascade Reaction of CO and Heteroallenes Mediated by Dinitrogen Hafnocene Complexes: The Indirect Effect of Nitride's Nucleophilicity. AB - A DFT mechanistic exploration of the reactivity of the dinitrogen hafnocene complex, [{(eta(5)-C5 H2 -1,2,4-Me3)2 Hf}2 (MU2-N2)], towards mixtures of CO/CO2 and CO/OCNtBu is reported. The crucial role of the nitride intermediate is highlighted, as well as the importance of the bridging mode of the cyanate ligand between the two Hf metal atoms throughout the process. Interestingly, the CO2 addition to the nitride intermediate occurs through an outer-sphere transition state, whereas the addition of the heteroallene is governed by the steric congestion imposed by cyclopentadienyl ligands. PMID- 26852716 TI - Mutant bacterial sodium channels as models for local anesthetic block of eukaryotic proteins. AB - Voltage gated sodium channels are the target of a range of local anesthetic, anti epileptic and anti-arrhythmic compounds. But, gaining a molecular level understanding of their mode of action is difficult as we only have atomic resolution structures of bacterial sodium channels not their eukaryotic counterparts. In this study we used molecular dynamics simulations to demonstrate that the binding sites of both the local anesthetic benzocaine and the anti epileptic phenytoin to the bacterial sodium channel NavAb can be altered significantly by the introduction of point mutations. Free energy techniques were applied to show that increased aromaticity in the pore of the channel, used to emulate the aromatic residues observed in eukaryotic Nav1.2, led to changes in the location of binding and dissociation constants of each drug relative to wild type NavAb. Further, binding locations and dissociation constants obtained for both benzocaine (660 MUM) and phenytoin (1 MUM) in the mutant channels were within the range expected from experimental values obtained from drug binding to eukaryotic sodium channels, indicating that these mutant NavAb may be a better model for drug binding to eukaryotic channels than the wild type. PMID- 26852717 TI - Psychometric properties of the Itch Numeric Rating Scale in patients with moderate-to-severe plaque psoriasis. AB - BACKGROUND: Itching is a profoundly distressing symptom for many patients with psoriasis, but it has not been rigorously studied using validated tools for this condition. OBJECTIVES: This study investigated the psychometric properties of the Itch Numeric Rating Scale (Itch NRS), a single-item patient-reported outcome (PRO) measuring the worst itching severity due to psoriasis in the past 24 h. METHODS: Using disease-specific clinician-rated and PRO data from one phase II and three phase III randomized clinical studies of subjects with moderate-to severe plaque psoriasis, the Itch NRS was evaluated for test-retest reliability, construct validity and responsiveness. A responder definition was explored using anchor- and distribution-based methods. RESULTS: Test-retest reliability analyses supported the reproducibility of the measure (intraclass correlation coefficient range 0.71-0.74). To support the construct validity of the Itch NRS, large cross sectional correlations with the Dermatology Life Quality Index (DLQI) Symptoms and Feelings domain (r >= 0.60 at baseline and r >= 0.80 at week 12) supported a priori hypotheses, while large correlations (r >= 0.71) between changes in Itch NRS scores and changes in DLQI Symptoms and Feelings domain scores from baseline to week 12 established responsiveness. A 4-point change was optimal for demonstrating a level of clinically meaningful improvement in itch severity after 12 weeks of treatment, which corresponds with marked clinical improvements in plaque psoriasis. CONCLUSIONS: The Itch NRS demonstrated sufficient reliability, validity and responsiveness, and appropriate interpretation standards for evaluating change over time in itch severity among patients with moderate-to severe plaque psoriasis when validated using clinical trial data for this condition. PMID- 26852719 TI - A Historical Perspective on the Role of Functional Lines of Block in the Re entrant Circuit of Ventricular Tachycardia. AB - The ablation strategy for ventricular tachycardia (VT) rapidly evolved from an entrainment mapping approach for identification of the critical isthmus of the re entrant circuit during monomorphic VT, toward a substrate-based approach aiming to ablate surrogate markers of the circuit during sinus rhythm in hemodynamically nontolerated and polymorphic VT. The latter approach implies an assumption that the circuits responsible for the arrhythmia are anatomical or fixed, and present during sinus rhythm. Accordingly, the lines of block delimiting the channels of the circuits are often considered fixed, although there is evidence that they are functional or more frequently a combination of fixed and functional. The electroanatomical substrate-based approach to VT ablation performed during sinus rhythm is increasingly adopted in clinical practice and often described as scar homogenization, scar dechanneling, or core isolation. However, whether the surrogate markers of the VT circuit during sinus rhythm match the circuit during arrhythmias remains to be fully demonstrated. The myocardial scar is a heterogeneous electrophysiological milieu with complex arrhythmogenic mechanisms that potentially coexist simultaneously. Moreover, the scar consists of different areas of diverse refractoriness and conduction. It can be misleading to limit the arrhythmogenic perspective of the myocardial scar to fixed or anatomical barriers held responsible for the re-entry circuit. Greater understanding of the role of functional lines of block in VT and the validity of the surrogate targets being ablated is necessary to further improve the technique and outcome of VT ablation. PMID- 26852718 TI - Unravelling the spatial variation of nitrous oxide emissions from a step-feed plug-flow full scale wastewater treatment plant. AB - Plug-flow activated sludge reactors (ASR) that are step-feed with wastewater are widely adopted in wastewater treatment plants (WWTPs) due to their ability to maximise the use of the organic carbon in wastewater for denitrification. Nitrous oxide (N2O) emissions are expected to vary along these reactors due to pronounced spatial variations in both biomass and substrate concentrations. However, to date, no detailed studies have characterised the impact of the step-feed configuration on emission variability. Here we report on the results from a comprehensive online N2O monitoring campaign, which used multiple gas collection hoods to simultaneously measure emission along the length of a full-scale, step fed, plug-flow ASR in Australia. The measured N2O fluxes exhibited strong spatial temporal variation along the reactor path. The step-feed configuration had a substantial influence on the N2O emissions, where the N2O emission factors in sections following the first and second step feed were 0.68% +/- 0.09% and 3.5% +/- 0.49% of the nitrogen load applied to each section. The relatively high biomass-specific nitrogen loading rate in the second section of the reactor was most likely cause of the high emissions from this section. PMID- 26852720 TI - Electron conjugation versus pi-pi repulsion in substituted benzenes: why the carbon-nitrogen bond in nitrobenzene is longer than in aniline. AB - Gas-phase electron diffraction experiments show that the C-N bond in aniline (1.407 A) is significantly shorter than in nitrobenzene (1.486 A). It is known that the amino group is electron-donating and the nitro group is electron withdrawing, and both substitution groups can effectively conjugate with benzene. Thus, it is puzzling why the C-N bond in nitrobenzene is even longer than the single C-N bond in methylamine (1.472 A). In this work, we performed computations by strictly localizing the pi electrons with the block-localized wavefunction (BLW) method, which is a variant of ab initio valence bond theory. Geometry optimizations of electron-localized states, where the conjugation over the C-N bond is quenched, show that the conjugation in nitrobenzene is only half of the conjugation in aniline. But even in optimal electron-localized states, the C-N bond in nitrobenzene is still 0.074 A longer than in aniline. As a consequence, it is indeed not the pi conjugation which is responsible for the disparity of the C-N bond distances in these systems. Instead, we demonstrated that the pi-pi repulsion, which is contributed by both Pauli exchange and electrostatic interaction, plays the key role in this "abnormal" behavior. Notably, the pi resonance within the nitro group generates a considerable dipole, which repels the pi electrons in the benzene ring. The deactivation of the resonance within the nitro group significantly shortens the C-N bond by 0.06 A. The unfavorable pi pi electrostatic repulsion is further exemplified by N2O4. In fact, the destabilizing pi-pi repulsion is ubiquitous but largely neglected in conjugated systems where only the stabilizing conjugation is the focus. Experimental phenomena such as the C-N bond distances in aniline and nitrobenzene result from the balance of both stabilizing and destabilizing forces. PMID- 26852721 TI - Between disruption and continuity: challenges in maintaining the 'biographical we' when caring for a partner with a severe, chronic illness. AB - Chronic obstructive pulmonary disease (COPD) is a progressive illness that changes the lives of patients and their spouses dramatically. The aim of this paper is to show how spouses of COPD patients integrate their tasks as informal carers with their role as spouses and the tensions and challenges involved in this. The study draws on qualitative interviews with spouses of COPD patients, recruited from the patient pool of ambulatory pulmonary services of two hospitals in Oslo, Norway. The spouses described their great efforts to re-establish normality and continuity in their everyday lives. Accomplishing this was a delicate process because they faced several dilemmas in this work. They balanced the need to sustain the independence and integrity of both parties against the need to ensure safety and deal with the progression of the illness. We propose 'biographical we' as a concept that can highlight the great effort spouses put into establishing a sense of continuity in their lives. In times when healthcare policy involves mobilising informal caregiving resources, an awareness of the complexity of caregiving relationships is crucial when developing appropriate support for informal carers. PMID- 26852722 TI - Light adaptation does not prevent early retinal abnormalities in diabetic rats. AB - The aetiology of diabetic retinopathy (DR), the leading cause of blindness in the developed world, remains controversial. One hypothesis holds that retinal hypoxia, exacerbated by the high O2 consumption of rod photoreceptors in the dark, is a primary cause of DR. Based on this prediction we investigated whether early retinal abnormalities in streptozotocin-induced diabetic rats are alleviated by preventing the rods from dark adapting. Diabetic rats and their non diabetic littermates were housed in a 12:12 hour light-dim light photocycle (30 lux during the day and 3 lux at night). Progression of early retinal abnormalities in diabetic rats was assessed by monitoring the ERG b-wave and oscillatory potentials, Muller cell reactive gliosis, and neuronal cell death, as assayed by TUNEL staining and retinal thickness at 6 and 12 weeks after diabetes induction. Maintaining diabetic animals in a dim-adapting light did not slow the progression of these neuronal and glial changes when compared to diabetic rats maintained in a standard 12:12 hour light-dark photocycle (30 lux during the day and 0 lux at night). Our results indicate that neuronal and glial abnormalities in early stages of diabetes are not exacerbated by rod photoreceptor O2 consumption in the dark. PMID- 26852724 TI - Managing the risks of vaccine hesitancy and refusals. PMID- 26852725 TI - New antibiotic development: the need versus the costs. PMID- 26852723 TI - The effect of heterogeneity in uptake of the measles, mumps, and rubella vaccine on the potential for outbreaks of measles: a modelling study. AB - BACKGROUND: Vaccination programmes to prevent outbreaks after introductions of infectious people aim to maintain the average number of secondary infections per infectious person at one or less. We aimed to assess heterogeneity in vaccine uptake and other characteristics that, together with non-random mixing, could increase this number and to evaluate strategies that could mitigate their impact. METHODS: Because most US children attend elementary school in their own neighbourhoods, surveys of children entering elementary school (age 5 years before Sept 1) allow assessment of spatial heterogeneity in the proportion of children immune to vaccine-preventable diseases. We used data from a 2008 school entry survey by the Immunization Division of the California Department of Public Health to obtain school addresses; numbers of students enrolled; proportions of enrolled students who had received one or two doses of the measles, mumps, and rubella (MMR) vaccine; and proportions with medical or personal-belief exemptions. Using a mixing model suitable for spatially-stratified populations, we projected the expected numbers of secondary infections per infectious person for measles, mumps, and rubella. We also mapped contributions to this number for measles in San Diego County's 638 elementary schools and its largest district, comprising 200 schools (31%). We then modelled the effect on measles' realised reproduction number (RV) of the following plausible interventions: vaccinating all children with personal-belief exemptions, increasing uptake by 10% to 50% in all low-immunity schools (<90% of students immune) or in only influential (effective daily contact rates >3 or contacts inter-school >30%) low-immunity schools, and increasing private school uptake to the public school average. FINDINGS: In 2008, 39 132 children began elementary school in San Diego County, CA, USA. At entry to school, 97% had received at least one dose of the MMR vaccine, with 2.5% having personal-belief exemptions. We note substantial heterogeneity in immunity throughout the county. Although the average population immunities for measles, mumps, and rubella (92%, 87%, 92%) were similar to the population-immunity thresholds in homogeneous, randomly-mixing populations (91%, 88%, 76%), after accounting for heterogeneity and non-random mixing, the basic reproduction numbers increased by 70%, meaning that introduced pathogens could cause outbreaks. The impact of our modelled interventions ranged from negligible to a nearly complete reduction in the outbreak potential of measles. The most effective intervention to lower the realised reproduction number (RV 3.39) was raising immunity by 50% in 114 schools with low immunity (RV 1.02), but raising immunity by this level in only influential, low-immunity schools also was effective (RV 2.02). The effectiveness of vaccinating the 972 children with personal-belief exemptions was similar to that of targeting all low-immunity schools (RV 1.11). Targeting only private schools had little effect. INTERPRETATION: Our findings suggest that increasing vaccine uptake could prevent outbreaks such as that of measles in San Diego in 2008. Vaccinating children with personal-belief exemptions was one of the most effective interventions that we modelled, but further research on mixing in heterogeneous populations is needed. FUNDING: None. PMID- 26852727 TI - Identification of Zika virus vectors and implications for control. PMID- 26852726 TI - Efficacy and safety of oral solithromycin versus oral moxifloxacin for treatment of community-acquired bacterial pneumonia: a global, double-blind, multicentre, randomised, active-controlled, non-inferiority trial (SOLITAIRE-ORAL). AB - BACKGROUND: Community-acquired bacterial pneumonia (CABP) is a leading cause of morbidity and mortality, and treatment recommendations, each with specific limitations, vary globally. We aimed to compare the efficacy and safety of solithromycin, a novel macrolide, with moxifloxacin for treatment of CABP. METHODS: We did this global, double-blind, double-dummy, randomised, active controlled, non-inferiority trial at 114 centres in North America, Latin America, Europe, and South Africa. Patients (aged >=18 years) with clinically and radiographically confirmed pneumonia of Pneumonia Outcomes Research Team (PORT) risk class II, III, or IV were randomly assigned (1:1), via an internet-based central block randomisation procedure (block size of four), to receive either oral solithromycin (800 mg on day 1, 400 mg on days 2-5, placebo on days 6-7) or oral moxifloxacin (400 mg on days 1-7). Randomisation was stratified by geographical region, PORT risk class (II vs III or IV), and medical history of asthma or chronic obstructive pulmonary disease. The study sponsor, investigators, staff, and patients were masked to group allocation. The primary outcome was early clinical response, defined as an improvement in at least two of four symptoms (cough, chest pain, sputum production, dyspnoea) with no worsening in any symptom at 72 h after the first dose of study drug, with a 10% non inferiority margin. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT-01756339. FINDINGS: Between Jan 3, 2013, and Sept 24, 2014, we randomly assigned 860 patients to receive solithromycin (n=426) or moxifloxacin (n=434). Patients were followed up to days 28-35 after first dose. Solithromycin was non-inferior to moxifloxacin in achievement of early clinical response: 333 (78.2%) patients had an early clinical response in the solithromycin group versus 338 (77.9%) patients in the moxifloxacin group (difference 0.29, 95% CI -5.5 to 6.1). Both drugs had a similar safety profile. 43 (10%) of 155 treatment-emergent adverse events in the solithromycin group and 54 (13%) of 154 such events in the moxifloxacin group were deemed to be related to study drug. The most common adverse events, mostly of mild severity, were gastrointestinal disorders, including diarrhoea (18 [4%] patients in the solithromycin group vs 28 [6%] patients in the moxifloxacin group), nausea (15 [4%] vs 17 [4%] patients) and vomiting (ten [2%] patients in each group); and nervous system disorders, including headache (19 [4%] vs 11 [3%] patients) and dizziness (nine [2%] vs seven [2%] patients). INTERPRETATION: Oral solithromycin was non-inferior to oral moxifloxacin for treatment of patients with CABP, showing the potential to restore macrolide monotherapy for this indication. FUNDING: Cempra. PMID- 26852728 TI - Systematic review of antibiotic resistance in acne: an increasing topical and oral threat. AB - Topical and oral antibiotics are routinely used to treat acne. However, antibiotic resistance is increasing, with many countries reporting that more than 50% of Propionibacterium acnes strains are resistant to topical macrolides, making them less effective. We reviewed the current scientific literature to enable proposal of recommendations for antibiotic use in acne treatment. References were identified through PubMed searches for articles published from January, 1954, to March 7, 2015, using four multiword searches. Ideally, benzoyl peroxide in combination with a topical retinoid should be used instead of a topical antibiotic to minimise the impact of resistance. Oral antibiotics still have a role in the treatment of moderate-to-severe acne, but only with a topical retinoid, benzoyl peroxide, or their combination, and ideally for no longer than 3 months. To limit resistance, it is recommended that benzoyl peroxide should always be added when long-term oral antibiotic use is deemed necessary. The benefit-to-risk ratio of long-term antibiotic use should be carefully considered and, in particular, use alone avoided where possible. There is a need to treat acne with effective alternatives to antibiotics to reduce the likelihood of resistance. PMID- 26852729 TI - Tuning the carrier concentration using Zintl chemistry in Mg3Sb2, and its implications for thermoelectric figure-of-merit. AB - Zintl compounds are potential candidates for efficient thermoelectric materials, because typically they are small band gap semiconductors. In addition, such compounds allow fine tuning of the carrier concentration by chemical doping for the optimization of thermoelectric performance. Herein, such tunability is demonstrated in Mg3Sb2-based Zintl compounds via Zn(2+) doping at the Mg(2+) site of the anionic framework (Mg2Sb2)(2-), in the series Mg3-xZnxSb2 (0 <= x <= 0.1). The materials have been successfully synthesized using the spark plasma sintering (SPS) technique. X-ray diffraction (XRD) analysis confirms a single solid solution phase of Mg3-xZnxSb2 (0 <= x <= 0.1). The thermoelectric properties are characterized by the Seebeck coefficient, electrical conductivity, and thermal conductivity measurements from 323 K to 773 K. Isoelectronic Zn substitution at the Mg site presents the controlled variation in the carrier concentration for optimizing the high power factor and reduced thermal conductivity. These results lead to a substantial increase in ZT of 0.37 at 773 K for a composition with x = 0.10 which is ~42% higher than undoped Mg3Sb2. The electronic transport data for the Mg3-xZnxSb2 (0 <= x <= 0.1) compound are analyzed using a single parabolic band model predicting that Mg2.9Zn0.1Sb2 exhibits a near-optimal carrier concentration for high ZT. The electronic structure of transport properties of these disordered Mg3-xZnxSb2 (0 <= x <= 0.1) is also studied using density functional theory and the results obtained are in good agreement with experimental results. The low cost, lightness and non-toxicity of the constituent elements make these materials ideal for mid-temperature thermoelectric applications. PMID- 26852730 TI - Surface-based morphometry reveals distinct cortical thickness and surface area profiles in Williams syndrome. AB - Morphometric investigations of brain volumes in Williams syndrome (WS) consistently show significant reductions in gray matter volume compared to controls. Cortical thickness (CT) and surface area (SA) are two constituent parts of cortical gray matter volume that are considered genetically distinguishable features of brain morphology. Yet, little is known about the independent contribution of cortical CT and SA to these volumetric differences in WS. Thus, our objectives were: (i) to evaluate whether the microdeletion in chromosome 7 associated with WS has a distinct effect on CT and SA, and (ii) to evaluate age related variations in CT and SA within WS. We compared CT and SA values in 44 individuals with WS to 49 age- and sex-matched typically developing controls. Between-group differences in CT and SA were evaluated across two age groups: young (age range 6.6-18.9 years), and adults (age range 20.2-51.5 years). Overall, we found contrasting effects of WS on cortical thickness (increases) and surface area (decreases). With respect to brain topography, the between-group pattern of CT differences showed a scattered pattern while the between-group surface area pattern was widely distributed throughout the brain. In the adult subgroup, we observed a cluster of increases in cortical thickness in WS across the brain that was not observed in the young subgroup. Our findings suggest that extensive early reductions in surface area are the driving force for the overall reduction in brain volume in WS. The age-related cortical thickness findings might reflect delayed or even arrested development of specific brain regions in WS. PMID- 26852732 TI - Vaginal clear cell carcinoma in a Japanese Black cow. AB - During artificial insemination of an 18-year-old female Japanese Black cow, a mass that was of a hen's egg size was found in the vagina. On necropsy, the firm mass, measuring approximately 3.5 * 3.5 * 3.0 cm, was located at the superior region of the vagina. The cut surface of the mass was gray-white in color with occasional necrotic or hemorrhagic areas. Histologically, the mass was composed of tumor cells arranged in solid nests of various sizes with an occasional tubular structure separated by a delicate fibrovascular stroma. The tumor cells had a hypochromatic nucleus and abundant, faintly eosinophilic cytoplasm. The tumor cells contained diastase-sensitive periodic acid-Schiff positive granules. Immunohistochemically, tumor cells were positive for cytokeratin AE1/AE3, CAM5.2 and carcinoembryonic antigen, but not for vimentin, p63, estrogen receptor-alpha, progesterone receptor, alpha-smooth muscle actin, neuron-specific enolase, S-100 protein and chromogranin A. On the basis of these findings, the tumor was diagnosed as a clear cell carcinoma of the vagina. PMID- 26852733 TI - Intermolecular interactions and proton transfer in the hydrogen halide-superoxide anion complexes. AB - The superoxide radical anion O2(-) is involved in many important chemical processes spanning different scientific disciplines (e.g., environmental and biological sciences). Characterizing its interaction with various substrates to help elucidate its rich chemistry may have far reaching implications. Herein, we investigate the interaction between O2(-) (X[combining tilde] (2)Pig) and the hydrogen halides (X[combining tilde] (1)Sigma) with coupled-cluster theory. In contrast to the short (1.324 A) hydrogen bond formed between the HF and O2(-) monomers, a barrierless proton transfer occurs for the heavier hydrogen halides with the resulting complexes characterized as long (>1.89 A) hydrogen bonds between halide anions and the HO2 radical. The dissociation energy with harmonic zero-point vibrational energy (ZPVE) for FHO2(-) (X[combining tilde] (2)A'') -> HF (X[combining tilde] (1)Sigma) + O2(-) (X[combining tilde] (2)Pig) is 31.2 kcal mol(-1). The other dissociation energies with ZPVE for X(-)HO2 (X[combining tilde] (2)A'') -> X(-) (X[combining tilde] (1)Sigma) + HO2 (X[combining tilde] (2)A'') are 25.7 kcal mol(-1) for X = Cl, 21.9 kcal mol(-1) for X = Br, and 17.9 kcal mol(-1) for X = I. Additionally, the heavier hydrogen halides can form weak halogen bonds H-XO2(-) (X[combining tilde] (2)A'') with interaction energies including ZPVE of -2.3 kcal mol(-1) for HCl, -8.3 kcal mol(-1) for HBr, and -16.7 kcal mol(-1) for HI. PMID- 26852731 TI - Evaluation of response to restraint stress by salivary corticosterone levels in adult male mice. AB - Saliva as a sampling method is a low invasive technique for the detection of physiologically active substances, as opposed to sampling the plasma or serum. In this study, we obtained glucocorticoids transferred from the blood to the saliva from mice treated with 2.0 mg/kg via an intraperitoneal injection of cortisol. Next, to evaluate the effect of restraint stress using mouse saliva-collected under anesthesia by mixed anesthetic agents-we measured plasma and salivary corticosterone levels at 60 min after restraint stress. Moreover, to evaluate salivary corticosterone response to stress in the same individual mouse, an adequate recovery period (1, 3 and 7 days) after anesthesia was examined. The results demonstrate that exogenous cortisol was detected in the saliva and the plasma, in mice treated with cortisol. Restraint stress significantly increased corticosterone levels in both the plasma and saliva (P<0.001). Monitoring the results of individual mice showed that restraint stress significantly increased salivary corticosterone levels in all three groups (1-, 3- and 7-day recovery). However, the statistical evidence of corticosterone increase is stronger in the 7 day recovery group (P<0.001) than in the others (P<0.05). These results suggest that the corticosterone levels in saliva reflect its levels in the plasma, and salivary corticosterone is a useful, less-invasive biomarker of physical stress in mice. The present study may contribute to concepts of Reduction and Refinement of the three Rs in small animal experiments. PMID- 26852734 TI - Restoring a nearly free-standing character of graphene on Ru(0001) by oxygen intercalation. AB - Realization of a free-standing graphene is always a demanding task. Here we use scanning probe microscopy and spectroscopy to study the crystallographic structure and electronic properties of the uniform nearly free-standing graphene layers obtained by intercalation of oxygen monolayer in the "strongly" bonded graphene/Ru(0001) interface. Spectroscopic data show that such graphene layer is heavily p-doped with the Dirac point located at 552 meV above the Fermi level. Experimental data are understood within density-functional theory approach and the observed effects are in good agreement with the theoretical data. PMID- 26852735 TI - The association of depressed angiogenic factors with reduced capillary density in the Rhesus monkey model of myocardial ischemia. AB - Depressed capillary density is associated with myocardial ischemic infarction, in which hypoxia-inducible factor 1alpha (HIF-1alpha) is increased. The present study was undertaken to examine changes in the angiogenic factors whose expression is regulated by HIF-1 and their relation to the depressed capillary density in the Rhesus monkey model of myocardial ischemic infarction. Male Rhesus monkeys 2-3 years old were subjected to myocardial ischemia by permanent ligation of left anterior descending (LAD) artery leading to the development of myocardial infarction. Eight weeks after LAD ligation, copper concentrations, myocardial histological changes and capillary density were examined, along with Western blot and immunohistochemical analysis of angiogenic factors and detection of HIF-1 activity. Capillary density was significantly decreased but the concentrations of HIF-1alpha and HIF-1beta were significantly increased in the infarct area. However, the levels of mRNA and protein for VEGF and VEGFR1 were significantly decreased. Other HIF-1 regulated angiogenic factors, including Tie-2, Ang-1 and FGF-1, were also significantly depressed, but vascular destabilizing factor Ang-2 was significantly increased. Copper concentrations were depressed in the infarct area. Copper-independent HIF-1 activity was increased shown by the elevated mRNA level of IGF-2, a HIF-1 target gene. Removal of copper by a copper chelator, tetraethylenepentamine, from primary cultures of neonatal rat cardiomyocytes also suppressed the expression of HIF-1 regulated VEGF and BNIP3, but not IGF-2. The data suggest that under ischemic conditions, copper loss suppressed the expression of critical angiogenic genes regulated by HIF-1, but did not affect copper-independent HIF-1 activation of gene expression. This copper-dependent dysregulation of angiogenic gene expression would contribute to the pathogenesis of myocardial ischemic infarction. PMID- 26852736 TI - One-Step Derivatization of Reducing Oligosaccharides for Rapid and Live-Cell Compatible Chelation-Assisted CuAAC Conjugation. AB - We report a new reagent for the functionalization of unprotected oligosaccharides with a picolyl azide group at the anomeric position for chelation-assisted copper catalyzed alkyne-azide cycloaddition (CuAAC) glycoconjugation. We show that oligosaccharides functionalized with this moiety react with an apparent second order rate constant of 193 m(-1) s(-1) and can be used to functionalize biomolecules bearing alkyne moieties introduced through metabolic labeling, including in live cells. PMID- 26852737 TI - COPD and the microbiome. AB - Traditional culture techniques confirm that bacteria have an important role in Chronic Obstructive Pulmonary Disease (COPD). In individuals with COPD, acquisition of novel bacterial strains is associated with onset of acute exacerbation of COPD, which leads to further lung dysfunction and enormous health care costs. Recent study of the human microbiome, the total composite of the bacteria on the human body, posited the microbiome as the last human organ studied, as the microbiome performs a multitude of metabolic functions absent in the human genome. The largest project to study the human microbiome was the National Institutes of Health (NIH) human microbiome project (HMP) started in 2007 to understand the 'normal' microbiome. However due to the presumption that the healthy human lung was sterile, the respiratory tract was not included in that study. The advent of next-generation sequencing technologies has allowed the investigation of the human respiratory microbiome, which revealed that the healthy lung does have a robust microbiome. Subsequent studies in individuals with COPD revealed that the microbiome composition fluctuates with severity of COPD, composition of the individual aero-digestive tract microbiomes, age, during an acute exacerbation of COPD and with the use of steroids and/or antibiotics. Understanding the impact of the microbiome on COPD progression and risk of exacerbation will lead to directed therapies for prevention of COPD progression and exacerbation. PMID- 26852739 TI - Skeletal response to diet with soya bean seeds used as primary source of protein in growing broiler chickens. AB - The study was conducted using 120 commercial broiler chicks (Ross 308) randomly allocated to two experimental groups. The experimental diets, differing only in protein source, either solvent-extracted soya bean meal (SBM) or traditional (non genetically modified) full-fat soya bean seeds (FFS), were prepared using practical corn-based formulation designed to meet nutritional requirements of broilers. Performance parameters were monitored weekly. Also, the subjects were evaluated daily for overt changes in skeletal anatomy and gait physiology. Randomly selected chickens from each group (seven males and seven females) were euthanized at 2, 3, 4 and 6 weeks of age, and bone specimens were collected for further study. Bone mineral density (BMD) and bone mineral content (BMC) were determined in tibiotarsal bones. Broilers fed FFS diet showed retarded growth rate and decreased feed intake (both p < 0.001). Both BMD and BMC parameters were significantly lower (p < 0.05) in bones of chickens from the FFS group in comparison with the SBM group. The chickens fed the FFS diet showed higher incidence of skeletal pathology including angular deformities and torticollis (both p < 0.01). Of note, cases of torticollis were observed only in FFS group. In many cases, skeletal abnormalities resulted in considerable changes in gait pattern, and in some instances, the pathology of leg bones was so advanced that the affected individuals were unable to walk, but this deformity was not seen in SBM group. From this study, it can be inferred that raw soya beans contain factors that have some specific detrimental effects on skeletal system of chickens. PMID- 26852740 TI - A Lysosome-Targeting Fluorescence Off-On Probe for Imaging of Nitroreductase and Hypoxia in Live Cells. AB - A lysosome-targeting fluorescent off-on probe has been developed by one-step synthesis for detecting lysosomal nitroreductase and hypoxia. The probe is constructed by incorporating morpholine (a lysosome-targeting unit) into 4-nitro 1,8-naphthalimide (as a fluorochrome and specific substrate for nitroreductase), and the detection mechanism is based on the nitroreductase-catalyzed reduction of the probe to 4-amino-1,8-naphthalimide, accompanied by a large fluorescence enhancement at a wavelength of 543 nm. The probe shows an accurate lysosome targeting ability with high selectivity and sensitivity to nitroreductase (detection limit: 2.2 ng mL-1 ). Notably, the probe has been used to image the change of lysosomal nitroreductase in live cells during hypoxia, revealing that the increase of nitroreductase in lysosomes may be smaller than that in the cytoplasm. In addition, the probe is expected to be useful for studying the function of nitroreductase in the acidic organelle of lysosomes. PMID- 26852738 TI - Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward. AB - The central melanocortin (MC) system mediates its effects on food intake via MC3 (MC3R) and MC4 receptors (MC4R). Although the role of MC4R in meal size determination, satiation, food preference, and motivation is well established, the involvement of MC3R in the modulation of food intake has been less explored. Here, we investigated the role of MC3R on the incentive motivation for food, which is a crucial component of feeding behavior. Dopaminergic neurons within the ventral tegmental area (VTA) have a crucial role in the motivation for food. We here report that MC3Rs are expressed on VTA dopaminergic neurons and that pro opiomelanocortinergic (POMC) neurons in the arcuate nucleus of the hypothalamus (Arc) innervate these VTA dopaminergic neurons. Our findings show that intracerebroventricular or intra-VTA infusion of the selective MC3R agonist gammaMSH increases responding for sucrose under a progressive ratio schedule of reinforcement, but not free sucrose consumption in rats. Furthermore, ex vivo electrophysiological recordings show increased VTA dopaminergic neuronal activity upon gammaMSH application. Consistent with a dopamine-mediated effect of gammaMSH, the increased motivation for sucrose after intra-VTA infusion of gammaMSH was blocked by pretreatment with the dopamine receptor antagonist alpha flupenthixol. Taken together, we demonstrate an Arc POMC projection onto VTA dopaminergic neurons that modulates motivation for palatable food via activation of MC3R signaling. PMID- 26852742 TI - Topological modification of the electronic structure by Bi-bilayers lying deep inside bulk Bi2Se3. AB - We observe the modified surface states of an epitaxial thin film of a homologous series of (Bi2)m(Bi2Se3)n, as a topological insulator (TI), by angle-resolved photoemission spectroscopy measurements. A thin film with m : n = 1 : 3 (Bi8Se9) has been grown with Bi2 bilayers embedded every other three quintuple layers (QLs) of Bi2Se3. Despite the reduced dimension of continuous QLs due to the Bi2 heterolayers, we find that the topological surface states stem from the inverted Bi and Se states and the topologically nontrivial structures are mainly based on the prototype of 3D TI Bi2Se3 without affecting the overall topological order. PMID- 26852741 TI - The interactive contributions of Na(+) /K(+) -ATPase and nitric oxide synthase to sweating and cutaneous vasodilatation during exercise in the heat. AB - KEY POINTS: Nitric oxide synthase (NOS) contributes to sweating and cutaneous vasodilatation during exercise in the heat. Similarly, reports show that Na(+) /K(+) -ATPase activation can modulate sweating and microvascular circulation. In light of the fact that NO can activate Na(+) /K(+) -ATPase, we evaluated whether there is an interaction between Na(+) /K(+) -ATPase and NOS in the regulation of heat loss responses during an exercise-induced heat stress. We demonstrate that Na(+) /K(+) -ATPase and NOS do not synergistically influence local forearm sweating during moderate intensity (fixed rate of metabolic heat production of 500 W) exercise in the heat (35 degrees C). Conversely, we show an interactive role between NOS and Na(+) /K(+) -ATPase in the modulation of cutaneous vasodilatation. These findings provide novel insight regarding the mechanisms underpinning the control of sweating and cutaneous vasodilatation during exercise in the heat. Given that ouabain may be prescribed as a cardiac glycoside in clinical settings, potential heat loss impairments with ouabain administration should be explored. ABSTRACT: Nitric oxide (NO) synthase (NOS) contributes to the heat loss responses of sweating and cutaneous vasodilatation. Given that NO can activate Na(+) /K(+) -ATPase, which also contributes to sweating and microvasculature regulation, we evaluated the separate and combined influence of Na(+) /K(+) -ATPase and NOS on sweating and cutaneous vasodilatation. Thirteen young (23+/-3 years) males performed two 30 min semi-recumbent cycling bouts in the heat (35 degrees C) at a fixed rate of metabolic heat production (500 W) followed by 20 and 40 min recoveries, respectively. Local sweat rate (LSR) and cutaneous vascular conductance (CVC) were measured at four forearm skin sites continuously perfused via intradermal microdialysis with either: (1) lactated Ringer solution (Control); (2) 6 m? ouabain (Ouabain), a Na(+) /K(+) -ATPase inhibitor; (3) 10 m? l-N(G) -nitroarginine methyl ester (l-NAME), a NOS inhibitor; or (4) 6 m? ouabain and 10 m? l-NAME (Ouabain+l-NAME). At the end of both exercise bouts relative to Control, LSR was attenuated with Ouabain (54 60%), l-NAME (12-13%) and Ouabain+l-NAME (68-74%; all P < 0.05). Moreover, the sum of attenuations from Control induced by independent administration of Ouabain and l-NAME was similar to the combined infusion of Ouabain+l-NAME (both P >= 0.74). Compared to Control, CVC at the end of both exercise bouts was similar with Ouabain (both P >= 0.30), but attenuated with l-NAME (%CVCmax reduction from Control, 24-25%). Furthermore, CVC at the Ouabain+l-NAME site (38-39%; all P < 0.01) was attenuated compared to Control and did not differ from baseline resting values (both P >= 0.81). We show that Na(+) /K(+) -ATPase and NOS do not synergistically mediate sweating, whereas they influence cutaneous blood flow in an interactive manner during exercise in the heat. PMID- 26852743 TI - Patient-centered decision making: the role of the baseline SNOT-22 in predicting outcomes for medical management of chronic rhinosinusitis. AB - BACKGROUND: For patients with chronic rhinosinusitis (CRS), the decision to elect continued medical management vs surgery is complex and involves tradeoffs between benefits, risks, and overall effectiveness of each therapy. The purpose of this study is to investigate whether baseline disease-specific quality of life (QOL) can assist in predicting outcomes in patients with refractory CRS who elect continued medical management. METHODS: CRS patients electing medical management were enrolled in a prospective, multi-institutional cohort study. Patients were stratified into pretreatment 22-item Sino-Nasal Outcome Test (SNOT-22) subgroups based on 10-point score increments (eg, 10 to 19, 20 to 29, 30 to 39, etc.) to capture potential outcome differences by baseline SNOT-22 disease burden. The proportion of patients achieving minimal clinically important difference (MCID>=9 points) and relative improvement (%) for each score category were calculated. RESULTS: Seventy-five CRS patients with a mean +/- standard deviation pretreatment SNOT-22 score of 45.2 +/- 16.6 were followed for a mean of 14.9 months. The majority of participants electing medical therapy failed to improve 1 MCID (57%) with a mean relative score improvement of 16%. Overall, 37% of patients maintained baseline SNOT-22 QOL status, whereas 20% of patients deteriorated >1 MCID. When treatment crossover patients (to endoscopic sinus surgery [ESS]) were included (n = 117), approximately 1 in 4 (27%) patients achieved an MCID. CONCLUSION: Results from this study suggest that the majority of CRS patients electing ongoing medical management with low baseline disease specific QOL impairment maintain stable QOL with continued medical management. Furthermore, of CRS patients electing ongoing medical therapy, approximately 1 in 4 patients achieved MCID, whereas 1 in 5 experienced deterioration by >1 MCID. PMID- 26852746 TI - Obituary: David Alastair Flockhart , MD, PhD. PMID- 26852745 TI - Identifying 24 h variation in the pharmacokinetics of levofloxacin: a population pharmacokinetic approach. AB - AIM: The objective of this study was to investigate whether the pharmacokinetics of orally administered levofloxacin show 24 h variation. Levofloxacin was used as a model compound for solubility and permeability independent absorption and passive renal elimination. METHODS: In this single centre, crossover, open label study, 12 healthy subjects received an oral dose of 1000 mg levofloxacin at six different time points equally divided over the 24 h period. Population pharmacokinetic modelling was used to identify potential 24 h variation in the pharmacokinetic parameters of this drug. RESULTS: The pharmacokinetics of levofloxacin could be described by a one compartment model with first order clearance and a transit compartment to describe drug absorption. The fit of the model was significantly improved when the absorption rate constant was described as a cosine function with a fixed period of 24 h, a relative amplitude of 47% and a peak around 08.00 h in the morning. Despite this variation in absorption rate constant, simulations of a once daily dosing regimen showed that tmax , Cmax and the area under the curve at steady-state were not affected by the time of drug administration. CONCLUSION: The finding that the absorption rate constant showed considerable 24 h variation may be relevant for drugs with similar physicochemical properties as levofloxacin that have a narrower therapeutic index. Levofloxacin, however, can be dosed without taking into account the time of day, at least in terms of its pharmacokinetics. PMID- 26852747 TI - Response to: 'A dose-response relationship between severity of disc degeneration and intervertebral disc height in the lumbosacral spine'. PMID- 26852748 TI - Autophagy regulates resistance of non-small cell lung cancer cells to paclitaxel. AB - Paclitaxel is a chemotherapeutic drug that is effective for treating non-small cell lung cancer (NSCLC). However, some NSCLCs are not sensitive to paclitaxel treatment with undetermined underlying molecular mechanisms. In this study, we found that paclitaxel dose-dependently activated Beclin-1 in 2 NSCLC cell lines, A549 and Calu-3. Inhibition of autophagy significantly increased the paclitaxel induced NSCLC cell death in a cell counting kit-8 (CCK-8) assay. Moreover, microRNA (miR)-216b levels were significantly downregulated in paclitaxel-treated NSCLC cells. Bioinformatics study showed that miR-216b targeted the 3'-UTR of Beclin-1 mRNA to inhibit its translation, which was confirmed by luciferase reporter assay. Together, these data suggest that paclitaxel may decrease miR 216b levels in NSCLC cells, which subsequently upregulates Beclin-1 to increase NSCLC cell autophagy to antagonize paclitaxel-induced cell death. Strategies that increase miR-216b levels or inhibit cell autophagy may improve the outcome of paclitaxel treatment in NSCLC therapy. PMID- 26852749 TI - miR-448 suppressed gastric cancer proliferation and invasion by regulating ADAM10. AB - MicroRNAs (miRNAs) are a class of short, noncoding RNAs that act a crucial role in tumor development. Previous studies showed that miR-448 expression was deregulated in many tumors. However, the role of miR-448 in gastric cancer (GC) remains unknown. In our study, we demonstrated that miR-448 expression was downregulated in GC tissues compared with the corresponding nontumor tissues. We also showed that miR-448 expression was downregulated in GC cell lines. Ectopic expression of miR-448 suppressed GC cell proliferation, colony formation, and invasion. Moreover, we identified A Disintegrin And Metalloproteinases 10 (ADAM10) as a direct target gene of miR-448 in GC cell. ADAM10 expression was upregulated in GC tissues and cells. Furthermore, the expression level of miR-448 was negatively correlated with the expression level of ADAM10 in GC tissues. Moreover, ADAM10 overexpression rescued the effect of miR-448-mediated GC cell proliferation, colony formation, and invasion. These results demonstrated that miR-448 might play as a tumor suppressor miRNA partly through targeting ADAM10 expression. PMID- 26852750 TI - miR-145 sensitizes gallbladder cancer to cisplatin by regulating multidrug resistance associated protein 1. AB - Gallbladder cancer (GBC) is the most common malignancy in biliary tract with poor prognosis. Due to its high chemoresistance, systemic chemotherapies have had limited success in treating GBC patients. MicroRNAs (miRNAs) are emerging novel regulators of chemoresistance, which modulate the expression of drug resistance related genes. In this study, we investigated the association between miR-145 expression and cisplatin sensitivity by both in vivo and in vitro analysis. Quantitative PCR (q-PCR) analysis indicated an increased miR-145 expression in GBC tissues. In addition, studies on GBC cell lines suggested an increased cisplatin efficacy with miR-145 overexpression, whereas decreasing miR-145 expression reduced cisplatin sensitivity. Further, we found that miR-145 accelerated MRP1 mRNA degradation by directly targeting its 3'-UTR and therefore caused increased cisplatin toxicity in GBC cells. Moreover, lower miR-145 and higher MRP1 expression levels predicted poor prognosis in GBC patients who received chemotherapy. Collectively, our findings established a rationale for using miR-145 expression as a biomarker to identify cisplatin-resistant GBC patients and propose that treatment strategies increasing the expression of miR 145 could be a new therapeutic approach for GBC patients. PMID- 26852753 TI - Enhancing UV-emissions through optical and electronic dual-function tuning of Ag nanoparticles hybridized with n-ZnO nanorods/p-GaN heterojunction light-emitting diodes. AB - ZnO nanorods (NRs) and Ag nanoparticles (NPs) are known to enhance the luminescence of light-emitting diodes (LEDs) through the high directionality of waveguide mode transmission and efficient energy transfer of localized surface plasmon (LSP) resonances, respectively. In this work, we have demonstrated Ag NP incorporated n-ZnO NRs/p-GaN heterojunctions by facilely hydrothermally growing ZnO NRs on Ag NP-covered GaN, in which the Ag NPs were introduced and randomly distributed on the p-GaN surface to excite the LSP resonances. Compared with the reference LED, the light-output power of the near-band-edge (NBE) emission (ZnO, lambda = 380 nm) of our hybridized structure is increased almost 1.5-2 times and can be further modified in a controlled manner by varying the surface morphology of the surrounding medium of the Ag NPs. The improved light-output power is mainly attributed to the LSP resonance between the NBE emission of ZnO NRs and LSPs in Ag NPs. We also observed different behaviors in the electroluminescence (EL) spectra as the injection current increases for the treatment and reference LEDs. This observation might be attributed to the modification of the energy band diagram for introducing Ag NPs at the interface between n-ZnO NRs and p-GaN. Our results pave the way for developing advanced nanostructured LED devices with high luminescence efficiency in the UV emission regime. PMID- 26852751 TI - Difference in expression patterns of placental cholesterol transporters, ABCA1 and SR-BI, in Meishan and Yorkshire pigs with different placental efficiency. AB - Cholesterol is a key cell membrane component and precursor of steroid hormones. The maternal cholesterol is an important exogenous cholesterol source for the developing embryos and its transportation is mediated by ABCA1 and SR-BI. Here we reported that during the peri-implantation period in pigs, ABCA1 was expressed by uterine luminal epithelium (LE) and interestingly, its expression was more abundantly in LE on mesometrial side of uterus. However, SR-BI was expressed primarily by LE, glandular epithelial cells (GE) and trophoblast cells (Tr). During the placentation period, the expression levels of ABCA1 and SR-BI proteins at epithelial bilayer and placental areolae were significantly higher in Chinese Meishan pigs compared to Yorkshire pigs. Consisitently, mRNA levels of HMGCR, the rate-limiting enzyme for cholesterol synthesis, were significantly higher in Meishan placentas than in Yorkshire placentas. Our findings revealed the routes of transplacental cholesterol transport mediated by ABCA1 and SR-BI in pigs and indicated that ABCA1 related pathway may participate in anchoring the conceptus to the mesometrial side of uterus. Additionally, an ABCA1 dependent compensatory mechanism related to the placental efficiency in response to the smaller placenta size in Meishan pigs was suggested. PMID- 26852754 TI - Sustainability assessment and prioritisation of e-waste management options in Brazil. AB - Brazil has an increasing rate of e-waste generation, but there are currently few adequate management systems in operation, with the largest share of Waste Electrical and Electronic Equipment (WEEE) going to landfill sites or entering informal chains. The National Solid Waste Policy (2010) enforces the implementation of reverse logistics systems under the shared responsibility of consumers, companies and governments. The objective of this paper is to assess sustainability and prioritise system alternatives for potential implementation in the metropolitan region of Rio de Janeiro. Sustainability criteria and decision alternatives were defined by elicitation of stakeholders. The adopted multicriteria approach combines Life Cycle Assessment with qualitative evaluations by a small sample of regional experts with knowledge of the problem. The recommended system consists of a hybrid WEEE collection scheme with delivery points at shops, metro stations and neighbourhood centres; a pre-treatment phase with the involvement of private companies, cooperatives and social enterprises; and full recycling of all components in the country. PMID- 26852755 TI - Cluster Headache as the Index Event in MS: A Case Report. AB - We report a 42-year-old woman who presented with cluster headache (CH) in association with other neurological symptoms as the index event of new onset multiple sclerosis (MS). Her initial symptoms were left-sided headache with ipsilateral lacrimation and nasal congestion associated with ipsilateral facial numbness. A subsequent similar headache attack was also associated with ipsilateral arm ataxia and gait ataxia. She had many additional short headache attacks without focal neurological symptoms. Her cluster-like headache attacks have not recurred since intiation of dimethyl fumarate. Our patient illustrates that cluster-like headache attacks can occur as a first symptom of MS, in our patient in association with other neurological symptoms. A striking finding in our patient was a large demyelinating lesion in the brachium pontis ipsilateral to the headaches, although additional supratentorial demyelinating lesions were also present. Although CH associated with MS is rare, our patient and the two other reported patients with MS and CH with similar ipsilateral brachium pontis lesions suggest that the lesions in this location may have played a role in the generation of the cluster-like attacks. PMID- 26852756 TI - Does the urea breath test predict eradication of Helicobacter pylori infection? AB - BACKGROUND AND AIM: Helicobacter pylori infection is common world-wide and has been linked to development of gastric and duodenal ulcers, gastric adenocarcinoma, and gastric lymphoma. However, antimicrobial resistance has decreased H. pylori eradication rates worldwide. This study aimed to evaluate the effect of -bacterial load on eradication rate. METHOD: This prospective study included 237 consecutive patients who presented to our institution with dyspeptic symptoms and underwent both upper endoscopy and urea breath tests (UBT). The patients were divided into three equal sized groups according to their UBT values. All subjects received a standard triple eradication regimen, followed by a bismuth- based quadruple eradication regimen if triple eradication was not successful. The three groups were compared with respect to age, endoscopic findings, sex, and eradication rates. RESULTS: Our results were consistent with those of previous studies : higher UBT values were associated with failure of standard 14-day triple treatment (p < 0.05). However, in patients who received a quadruple eradication regimen, differences between groups were not significant (p = 0.434). There was no relationship between UBT values and gastric pathologies (p = 0.751). Age and sex also did not differ significantly between groups (p = 0.061). CONCLUSIONS: Our study and others have found that high bacterial loads are negatively associated with achievement of eradication with triple treatment. However, differences between groups were not significant in patients who received a quadruple eradication regimen. Comparisons of treatment results according to bacterial density may be informative. The importance of H. pylori density should be further evaluated with new treatment protocols. PMID- 26852757 TI - The Effect of the iNOS Inhibitor S-Methylisothiourea and Hyperbaric Oxygen Treatment on Radiation Colitis in Rats. AB - INTRODUCTION: External radiotherapy is one of the main treatment modalities for a variety of malignancies. However, the lower gastrointestinal tract is sensitive to the ionizing radiation. Hyperbaric oxygen treatment (HOT) has been suggested as a viable treatment for refractory radiation colitis, but the effect of S Methylisothiourea (SMT) in the radiation colitis have not reported. To investigate the effect of SMT, HOT and the combination of both in an acute radiation-induced enterocolitis model. METHODS: Sixty Sprague-Dawley rats were divided randomly into five equal groups. A single dose of gamma irradiation (25 Gy) was administered through the colorectal region to anesthetized rats. In the control group, we applied 2 ml of saline solution intraperitoneally for five days. In the HOT group, 100-per-cent oxygen at 2.5 atm pressure was applied for five days. In the SMT group, 10 mg/kg/day of SMT was applied intraperitoneally for five days. In the HOT+SMT group, HOT and SMT were both applied in the same dosages as in the preceding two groups. At the end of five days, the rats were sacrificed and colon samples were collected for histological grading. Blood samples were collected to test for : tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), IL-1beta, transforming growth factor-beta (TGF-beta) and intercellular adhesion molecule-1 (ICAM-1) mRNA. RESULTS: The TNF-alpha, IL 1beta, IL-10 and TGF-beta levels were reduced by SMT, HOT and HOT+SMT applications (p < 0.05). However ICAM-1 mRNA levels were not significantly lower (p:0.19). The microscopic scores differed significantly between the SMT, HOT and HOT+SMT groups and the control group. There was significant improvement histologically, especially in the HOT+SMT group. When we compared the weight of the rats before and after the study, weight loss was significantly lower in the SMT, HOT and HOT+SMT groups compared with the control group (p < 0.05). CONCLUSION: HOT and SMT together were significantly more effective in preventing weight loss and in reducing inflammation and the severity of colitis histology when compared with HOT and SMT separately. PMID- 26852758 TI - Clinical scores for the prediction of esophageal varices in patients with liver cirrhosis. AB - INTRODUCTION: Esophageal bleeding is one of the most important and dramatic complications of liver cirrhosis in our everyday practice. Considering the costs of repeated upper endoscopy (UE) there is an increasing number of studies focusing on noninvasive para-meters for the assessment of esophageal varices (EV). PATIENTS AND METHODS: Retrospective study included 74 patients with alcoholic and viral liver cirrhosis treated at Clinic of Gastroenterology and Hepatology, Clinical Center of Serbia. The data were obtained from patients medical records including history, biochemical, ultrasonography and UE findings. RESULTS: The average value of the RLLD/INR for patients who showed evidence of EV during UE and in those who didn't was 10.46 +/- 3.09 and 12.24 +/- 3.43, respectively (p = 0.019, p < 0.05). Cutoff value (11.5) of RLLD/INR showed a sensitivity of 64.15% and specificity of 66.67% (1.92LR+, and 0.54 LR-, AUROC 0.639) for the detection of EV. The average value of PC/SBD for patients who showed evidence of EV during UE and in those who didn't was 619.79 +/- 492.96 and 1423.1 +/- 908.2, respectively (p = 0.0, p < 0.05). The average value of RLLD/SA was 5.5 +/- 0.17 and 4.57 +/- 0.17 (p = 0.015, p < 0.05) for patients who showed evidence of EV -during UE and in those who didn't, respectively. CONCLUSION: Noninvasive assessment of EV using scores based on ultrasonography and laboratory is simple, inexpensive, and could be a useful tool in limiting the number of repeated UE. PMID- 26852759 TI - Retreatment of Chronic Hepatitis C Infection with Telaprevir : Turkey Experience. AB - BACKGROUND AND AIMS: Patients with genotype 1 chronic hepatitis C virus (HCV) who do not have a sustained virologic response to therapy with peginterferon alfa and ribavirin have a low likelihood of success with retreatment. MATERIALS AND METHODS: Voluntary patients aged 18 and older with genotype-1 chronic HCV and with no exclusion criteria were -included. Treatment was organized as following: telaprevir was administered at a dose of 750 mg every 8 hours ; Peg-IFN alpha-2a was administered at a dose of 180 mcg per week and ribavirin was -administered at a dose of 1000-1200 mg per day. HCV-RNA levels were measured before treatment, at 4, 12, 24 weeks of treatment, after treatment and after 24 weeks of treatment. Sustained virologic response was defined as undetectable HCV-RNA after 24 weeks of treatment. RESULTS: Sustained virologic response was obtained in 37 patients (74%). Breakthrough (BT) or early relapse was seen in 6 patients (12%) in total. Treatment had to be discontinued because of treatment related adverse events in 7 patients (14%). CONCLUSION: Triple combination therapy including telaprevir is significantly better than classical Peg-IFN alpha and ribavirin therapy in patients with chronic hepatitis-C infection. PMID- 26852760 TI - Evaluation of oxidant/anti-oxidants status in patients with mild acute pancreatitis. AB - BACKGROUND AND AIM: Acute pancreatitis (AP), an inflammatory disorder of the pancreas, is associated with significant morbidity and mortality. The pathogenesis of AP has been suggested to -involve high oxidative stress (OS), combined with inadequate antioxidant status. We aimed to investigate the levels of serum total anti-oxidant status (TAS), total oxidant status (TOS) and ischemia modified albumin (IMA) in patients with mild AP2016. METHODS: Thirty subjects with mild AP and 29 healthy controls were enrolled into the study. The levels of TAS, TOS and IMA, C-reactive protein (CRP), high sensitivity CRP (hs-CRP) and fibrinogen were measured in both groups. RESULTS: TAS levels were significantly lower (p = 0.037), while IMA levels were significantly higher (p < 0.001) in patients, compared to controls. TOS levels were similar between two groups. Fibrinogen, CRP and hs-CRP levels were significantly higher in patients than those of controls (p < 0.001 for all parameters). IMA levels were positively correlated with amylase and lipase levels (r = 0.448, p = 0.001 and r = 0.469, p < 0.001, respectively). There was a negative correlation between TAS levels, and amylase and lipase levels (r = -0.277, p = 0.035 and r = -0.278, p = 0.034, respectively). CONCLUSION: OS is reported to be associated with the inflammatory process and the severity of AP. In our study, among OS parameters, an increase in IMA levels and a decrease in TAS levels were observed in mild AP patients. PMID- 26852761 TI - Irritable bowel syndrome and visceral hypersensitivity : risk factors and pathophysiological mechanisms. AB - Irritable bowel syndrome (IBS) is a common functional gastro-intestinal disorder, characterized by abdominal pain and altered intestinal motility. Visceral hypersensitivity is an important hallmark feature of IBS and is believed to underlie abdominal pain in patients with IBS. The two main risk factors associated with the development of IBS are gastrointestinal inflammation and psychological distress. On a peripheral level, visceral sensitivity seems to be modulated by several mechanisms. Immune cells in the mucosal wall, such as mast cells, and enterochromaffin cells may sensitize afferent nerves by release of their mediators. Furthermore, increased mucosal permeability, altered intestinal microflora and dietary habits may contribute to this feature. On a central level, an increased prevalence of psychiatric comorbidities is demonstrated in IBS patients, alongside alterations in the hormonal brain-gut axis, increased vigilance towards intestinal stimuli and functional and structural changes in the brain. The pathogenesis of IBS is complicated and multifactorial and the treatment remains clinically challenging. Dietary measures and symptomatic control are the cornerstones for IBS treatment and may be sufficient for patients experiencing mild symptoms, alongside education, reassurance and an effective therapeutic physician-patient relationship. New pharmacological therapies are aimed at interfering with mediator release and/or blockade of the relevant receptors within the gut wall, while modulation of the intestinal flora and diet may also be of therapeutic benefit. Tricyclic anti-depressants and serotonin reuptake inhibitors act both on a central and peripheral level by modulating pain signalling pathways. PMID- 26852762 TI - Risk factors for complications and mortality related to endoscopic procedures in adults. AB - BACKGROUND AND AIM: The objective of this study is to identify and describe risk factors and complications in endoscopic procedures. METHODS: This review presents the complications and the accompanying risk factors that were described in the selected full-text articles. The relevant full-text articles were found in Pubmed, ISI Web of Science and the CINAHL database. RESULTS: The search resulted in 238 abstracts, 50 of which were finally selected for full-text analysis. The different types of endoscopic procedures each have specific complications, but bleeding and perforation occur in all procedures. It was found that bleeding, perforation, cardiovascular and respiratory complications were common complications.Furthermore, morbidity and mortality have been associated with risk factors such as older age, high ASA class and sedation. CONCLUSION: Endoscopy is not without risk, although the prevalence of complications is low. Most complications seenin this analysis, are linked to known risk factors. Some complications might be preventable or avoidable, given a more systematic and comprehensive approach pre-, per- and postprocedural. The creation and implementation of an endoscopic safety checklist could be an -important supportive tool in lowering complications. PMID- 26852763 TI - Pharmacomechanical thrombectomy for salvage of TIPSS via successful -clearance of occlusive porto-splenic venous thrombosis. AB - Transjugular intrahepatic porto-systemic shunt (TIPSS) is increasingly used to treat chronic portal vein thrombosis. However shunt thrombosis is a recognised early complication, particularly in those with thrombophilia. We outline a case of non-cirrhotic portal hypertension secondary to chronic portal vein occlusion where TIPSS was successfully performed but rapidly complicated by shunt thrombosis with extension into the portal and splenic veins. Mechanical thrombectomy and low dose systemic pharmacological thrombolysis were of limited benefit. Combined pharmacomechanical thrombectomy with the Trellis system restored -patency of the TIPSS, portal and splenic veins, with resultant good flow into the TIPSS. The patient remains well three months post-procedure. We describe the first case where the Trellis system has been successfully used to clear occlusive porto-splenic thrombus and restore flow through a blocked TIPSS. PMID- 26852764 TI - Plesiomonas shigelloides : an extremely rare cause of Spontaneous Bacterial Peritonitis. AB - Plesiomonas shigelloides, a rare cause of gastroenteritis in humans, is a gram negative rod belonging to the Enterobacteriaceae family. In addition, it has also been implicated in extra-intestinal infection, but prevalence data on such infections have been limited to case reports. To date there has been only one published case of P. shigelloides causing spontaneous bacterial peritonitis (SBP). We describe another patient with P. shigelloides SBP and compare our findings with those from the original case. PMID- 26852765 TI - Familial alpha 1 antitrypsin deficiency cases that are diagnosed in adulthood. AB - Alpha 1 antitrypsin (AAT) deficiency is a hereditary disorder leading to severe lung and liver diseases worldwide. An accumulation of insoluble heterodimer AAT molecules in hepatocytes is the main cause of liver disorders. The most commonly detected allele worldwide is the PIMM allele, which fulfills the AAT function. The most common missing variant is PiZZ. Serum AAT level is a beneficial but not a reliable determinant for diagnosis. Liver biopsy yields more reliable results. AAT deficiency has no specific treatment. The only treatment modality in children with end stage liver disease is the hepatic transplant. We wanted to present in our article four cases from same family, diagnosed alpha-1 antitrypsindeficiency in adulthood. PMID- 26852766 TI - Portosystemic encephalopathy in an 86-year-old patient : a clinical challenge. AB - Abernethy malformations are rare vascular abnormalities, classified into two types : type 1 if the portal vein is absent, type 2 when the portal blood is diverted into vena cava through a hypoplastic portal vein. These conditions present symptoms related to portosystemic shunting, and usually become clinically evident in children or young adults. Here we report the first case of Abernethy malformation diagnosed in an 86-year-old female patient affected by portosystemicencephalopaty. PMID- 26852767 TI - Is there a difference between patients with rectal hyposensitivity having either constipation or anal incontinence? PMID- 26852769 TI - Reactivation of Resolved Hepatitis B virus Infection before the Relapse of Lymphoma : Immunosuppressive effect of the Lymphoproliferative disorders? AB - Hepatitis B virus (HBV) infection is a heterogeneous disease with distinct phases determined mainly by the interaction between virus replication and host immune response. HBV reactivation can occur spontaneously, developing resistance to antiviral treatment while the patient is undergoing treatment, after cessation of antiviral drugs, or be triggered by immunosuppressive drugs and chemotherapy. HBV reactivation can be severe and sometimes fatal because of liver failure. Here we report a patient with resolved HBV infection who presented with reactivation before being diagnosed with a relapse of non-Hodgkin lymphoma. PMID- 26852770 TI - Ciprofloxacin induced pancreatitis : Has this condition been overlooked? PMID- 26852771 TI - Fracture of an indwelling biliary catheter : a word of caution. PMID- 26852772 TI - Unusual reason of abdominal pain in a young female patient. PMID- 26852773 TI - Rabbit biocontrol and landscape-scale recovery of threatened desert mammals. AB - Funding for species conservation is insufficient to meet the current challenges facing global biodiversity, yet many programs use expensive single-species recovery actions and neglect broader management that addresses threatening processes. Arid Australia has the world's worst modern mammalian extinction record, largely attributable to competition from introduced herbivores, particularly European rabbits (Oryctolagus cuniculus) and predation by feral cats (Felis catus) and foxes (Vulpes vulpes). The biological control agent rabbit hemorrhagic disease virus (RHDV) was introduced to Australia in 1995 and resulted in dramatic, widespread rabbit suppression. We compared the area of occupancy and extent of occurrence of 4 extant species of small mammals before and after RHDV outbreak, relative to rainfall, sampling effort, and rabbit and predator populations. Despite low rainfall during the first 14 years after RHDV, 2 native rodents listed by the International Union for Conservation of Nature (IUCN), the dusky hopping-mouse (Notomys fuscus) and plains mouse (Pseudomys australis), increased their extent of occurrence by 241-365%. A threatened marsupial micropredator, the crest-tailed mulgara (Dasycercus cristicauda), underwent a 70 fold increase in extent of occurrence and a 20-fold increase in area of occupancy. Both bottom-up and top-down trophic effects were attributed to RHDV, namely decreased competition for food resources and declines in rabbit-dependent predators. Based on these sustained increases, these 3 previously threatened species now qualify for threat-category downgrading on the IUCN Red List. These recoveries are on a scale rarely documented in mammals and give impetus to programs aimed at targeted use of RHDV in Australia, rather than simply employing top-down threat-based management of arid ecosystems. Conservation programs that take big-picture approaches to addressing threatening processes over large spatial scales should be prioritized to maximize return from scarce conservation funding. Further, these should be coupled with long-term ecological monitoring, a critical tool in detecting and understanding complex ecosystem change. PMID- 26852774 TI - Analysis of Long-Chain Unsaturated Fatty Acids by Ionic Liquid Gas Chromatography. AB - Four ionic liquid (IL) columns, SLB-IL59, SLB-IL60, SLB-IL65, and SLB-IL111, were evaluated for more rapid analysis or improved resolution of long-chain methyl and ethyl esters of omega-3, omega-6, and additional positional isomeric and stereoisomeric blends of fatty acids found in fish oil, flaxseed oil, and potentially more complicated compositions. The three structurally distinct IL columns provided shorter retention times and more symmetric peak shapes for the fatty acid methyl or ethyl esters than a conventional polyethylene glycol column (PEG), resolving cis- and trans-fatty acid isomers that coeluted on the PEG column. The potential for improved resolution of fatty acid esters is important for complex food and supplement applications, where different forms of fatty acid can be incorporated. Vacuum ultraviolet detection contributed to further resolution for intricate mixtures containing cis- and trans-isomers, as exemplified in a fatty acid blend of shorter chain C18:1 esters with longer chain polyunsaturated fatty acid (PUFA) esters. PMID- 26852775 TI - A definite bite by the Ornamental Snake (Denisonia maculata) causing mild envenoming. AB - CONTEXT: Many bites from mildly venomous elapids occur but identification or presence of systemic envenoming is rarely confirmed. OBJECTIVE: To confirm systemic envenoming and binding of venom components to a commercial antivenom in a definite bite by the Ornamental Snake (Denisonia maculata) using enzyme immunoassays. CASE: A 9-year old boy was bitten by an identified Ornamental Snake. He developed nausea, vomiting, local pain, and swelling. He had a leucocytosis (white cell count, 20.8 * 10(9)/L), an elevated international normalised ratio (INR) of 1.6, but otherwise normal blood tests including D-Dimer and activated partial thromboplastin time. He was treated with Australian Black Snake antivenom because the commercial venom detection kit was positive for Black snake. He was admitted for 36 h with continuing local pain and swelling requiring parenteral analgesia. MATERIALS AND METHODS: Blood samples were collected with informed consent for measurement of venom and antivenom concentrations. Venom specific enzyme immunoassays were developed using the closely related D. devisi venom with Rabbit anti-Notechis (Tiger Snake) and anti-Tropidechis (Rough-scaled Snake) IgG antibodies to detect venom in serum. Standard curves for measured venom versus actual venom concentrations were made to interpolate Denisonia venom concentrations. In vitro procoagulant and anticoagulant activity of venom was assayed. RESULTS: Denisonia venom was detected in the pre-antivenom sample as 9.6 ng/mL D. devisi venom. No antigenic venom components were detected in post antivenom samples and there were high antivenom concentrations. D. devisi venom had mild in vitro procoagulant activity with a minimum concentration required to clot after 5 min of 2.5-5 MUg/mL and even weaker anticoagulant activity. CONCLUSIONS: Denisonia bites appear to cause local effects and possibly mild systemic envenoming (with only non-specific systemic symptoms and leucocytosis), confirmed by detection of antigenic venom components in blood. A significant coagulopathy does not appear to occur. PMID- 26852776 TI - Divergent Reactivity of N-Isocyanates with Primary and Secondary Amines: Access to Pyridazinones and Triazinones. AB - Cascade reactions for the synthesis of 1,2,4-triazinones and 5-aminopyridazinones are reported using alpha-ketocarbazones as N-isocyanate precursors and exploiting the divergent reactivity observed with primary and secondary amines. Triazinones were formed with primary amines, likely through addition of the amine on the N isocyanate, followed by cyclization (condensation) on the ketone. In contrast, such cyclization is impossible for secondary amines; this allows in situ formation of enamines, which, upon cyclization, generate 5-amino pyridazinones. This sequence further illustrates the versatility of N-isocyanates in heterocyclic synthesis and provides a rare example of carbon nucleophiles reacting with N-isocyanates. PMID- 26852777 TI - Use of modified barium swallow study to measure posterior airway space in obstructive sleep apnea. AB - Conclusion Measurement of the posterior airway space (PAS) using modified barium swallow (MBS) appears to correlate well with CT imaging. This data suggests MBS may be a low-cost alternative imaging modality to assess obstructive sleep apnea patients. Objectives Obstructive sleep apnea research has focused on imaging modalities that supplement polysomnography in evaluation of potential sites of airway obstruction. While several techniques have been used to assess the PAS, many incur significant costs and risks to the patient. This study proposes use of MBS as a simple modality to measure PAS. Advantages include its simplicity, lower radiation, and dynamic tongue base visualization, which may help predict surgical outcomes. It is hypothesized that cephalometric measurements obtained using MBS will correlate well with CT. Methods Thirty-six adult patients who underwent both CT imaging and MBS for head and neck cancer were included. Cephalometric measurements of the PAS were obtained using each imaging modality. Statistical analysis focused on correlating measurements taken using CT and MBS. Results The average PAS measurements were 12.53 +/- 1.81 mm and 12.80 +/- 1.75 mm by MBS and CT imaging, respectively. In comparing the two modalities, Pearson correlation between CT and MBS measurements revealed significant positive correlations between r = 0.769 and 0.937. PMID- 26852778 TI - Design and focus group evaluation of a bed-integrated weight measurement system for wheelchair users. AB - Regular weight monitoring is known to help with weight management, which is an important part of maintaining a healthy, active lifestyle. Unfortunately, weight monitoring is challenging for wheelchair users because the few scales that are available are expensive and very large. Consequently, wheelchair users typically learn their weight at infrequent visits to their healthcare providers, which likely contributes to higher prevalence of obesity-related health risks among this population. In this article, we describe the design and development of the Embedded Scale, or E-Scale, which is a bed-integrated bodyweight measuring system that allows a user to measure and track their weight. The E-Scale team followed a standard product development approach to build the E-Scale prototype. Bench testing results indicate that the performance of the prototype is on par with commercially available wheelchair scales (capacity = 1,200 lbs, accuracy = 1.73 lbs, and precision = +/- 0.35 lbs over one-fourth rated capacity). Institutional Review Board (IRB)-approved focus groups with 20 Veterans who use wheelchairs for mobility were conducted to gather feedback about the design, which was very positive. Development and testing results suggests the E-Scale technology is feasible and may provide a valuable tool to help wheelchair users manage their weight. PMID- 26852779 TI - Core-Shell Vanadium Modified Titania@beta-In2S3 Hybrid Nanorod Arrays for Superior Interface Stability and Photochemical Activity. AB - Core-shell rutile TiO2@beta-In2S3 and modified V-TiO2@beta-In2S3 were synthesized to develop bilayer systems to uphold charge transport via an effective and stable interface. Morphological studies revealed that beta-In2S3 was deposited homogeneously on V-TiO2 as compared to unmodified TiO2 nanorod arrays. X-ray photoelectron spectroscopy (XPS) and electron energy loss spectrometry studies verified the presence of various oxidation states of vanadium in rutile TiO2 and the vanadium surface was utilized for broadening the charge collection centers in host substrate layer and hole quencher window. Subsequently, X-ray diffraction, high-resolution transmission electron microscopy, and Raman spectra confirmed the rutile phases of TiO2 and modified V-TiO2 along with the phases of crystalline beta-In2S3. XPS valence band study explored the interaction of valence band quazi Fermi levels of beta-In2S3 with the conduction band quazi Fermi levels of modified V-TiO2 for enhanced charge collection at the interface. Photoelectrochemical studies show that the photocurrent density of V-TiO2@beta In2S3 is 1.42 mA/cm(2) (1.5AM illumination). Also, the frequency window for TiO2 was broadened by the vanadium modification in rutile TiO2 nanorod arrays, and the lifetime of the charge carrier and stability of the interface in V-TiO2@beta In2S3 were enhanced compared to the unmodified TiO2@beta-In2S3. These findings highlight the significance of modifications in host substrates and interfaces, which have profound implications on interphase stability, photocatalysis and solar-fuel-based devices. PMID- 26852780 TI - "You Get More Than You Give": Experiences of Community Partners in Facilitating Active Recreation with Individuals who have Complex Communication Needs. AB - Recreation is an essential part of life that provides enriching experiences that may define one's life course similar to careers or other interests. An understanding of the role of volunteers in active community-based recreational programs can help to generate ways to enhance participation and contribute to additional communication opportunities with people who have complex communication needs. Nine volunteers from two adaptive ski programs and one therapeutic horseback-riding program in the Northeast region of the United States participated in semi-structured interviews. Audio-recordings were transcribed and analyzed and resulted in five thematic areas: (a) benefits, (b) why individuals volunteer, (c) barriers, (d) successful program supports, and (e) who are the riders and skiers using AAC. The findings provided insight to support the notion that active community-based recreational activities foster an environment for communication, meaningful engagement, and social relationships between volunteers and people with complex communication needs. PMID- 26852781 TI - Binding and detoxification of chlorpyrifos by lactic acid bacteria on rice straw silage fermentation. AB - This investigation examined the reduction of pesticide residues on straw inoculated with lactic acid bacteria (LAB) during ensiling. Lactobacillus casei WYS3 was isolated from rice straw that contained pesticide residues. Non sterilized rice straw, which was inoculated with L. casei WYS3, showed increased removal of chlorpyrifos after ensiling, compared with rice straw that was not inoculated with L. casei WYS3 or sterilized rice straw. In pure culture, these strains can bind chlorpyrifos as indicated by high-performance liquid chromatography analysis. Viable L. casei WYS3 was shown to bind 33.3-42% of exogenously added chlorpyrifos. These results are similar to those of acid treated cells but less than those of heat-treated cells, which were found to bind 32.0% and 77.2% of the added chlorpyrifos respectively. Furthermore, gas chromatography-mass spectrometry analysis determined that L. casei WYS3 detoxified chlorpyrifos via P-O-C cleavage. Real-time polymerized chain reaction analysis determined that organophosphorus hydrolase gene expression tripled after the addition of chlorpyrifos to LAB cultures, compared with the control group (without chlorpyrifos). This paper highlights the potential use of LAB starter cultures for the detoxification and removal of chlorpyrifos residues in the environment. PMID- 26852782 TI - Biomass production, nutrient cycling, and carbon fixation by Salicornia brachiata Roxb.: A promising halophyte for coastal saline soil rehabilitation. AB - In order to increase our understanding of the interaction of soil-halophyte (Salicornia brachiata) relations and phytoremediation, we investigated the aboveground biomass, carbon fixation, and nutrient composition (N, P, K, Na, Ca, and Mg) of S. brachiata using six sampling sites with varying characteristics over one growing season in intertidal marshes. Simultaneously, soil characteristics and nutrient concentrations were also estimated. There was a significant variation in soil characteristics and nutrient contents spatially (except pH) as well as temporally. Nutrient contents in aboveground biomass of S. brachiata were also significantly differed spatially (except C and Cl) as well as temporally. Aboveground biomass of S. brachiata ranged from 2.51 to 6.07 t/ha at maturity and it was positively correlated with soil electrical conductivity and available Na, whereas negatively with soil pH. The K/Na ratio in plant was below one, showing tolerance to salinity. The aboveground C fixation values ranged from 0.77 to 1.93 C t/ha at all six sampling sites. This study provides new understandings into nutrient cycling-C fixation potential of highly salt-tolerant halophyte S. brachiata growing on intertidal soils of India. S. brachiata have a potential for amelioration of the salinity due to higher Na bioaccumulation factor. PMID- 26852783 TI - Low energy availability in exercising men is associated with reduced leptin and insulin but not with changes in other metabolic hormones. AB - Low energy availability, defined as low caloric intake relative to exercise energy expenditure, has been linked to endocrine alterations frequently observed in chronically energy-deficient exercising women. Our goal was to determine the endocrine effects of low energy availability in exercising men. Six exercising men (VO2peak: 49.3 +/- 2.4 ml . kg(-1) . min(-1)) underwent two conditions of low energy availability (15 kcal . kg(-1) fat-free mass [FFM] . day(-1)) and two energy-balanced conditions (40 kcal . kg(-1) FFM . day(-1)) in randomised order. During one low energy availability and one balanced condition, participants exercised to expend 15 kcal . kg(-1) FFM . day(-1); no exercise was conducted during the other two conditions. Metabolic hormones were assessed before and after each 4-day period. Following both low energy availability conditions, leptin (-53% to -56%) and insulin (-34% to -38%) were reduced (P < 0.05). Reductions in leptin and insulin were independent of whether low energy availability was attained with or without exercise (P > 0.80). Low energy availability did not significantly impact ghrelin, triiodothyronine, testosterone and IGF-1 (all P > 0.05). The observed reductions in leptin and insulin were in the same magnitude as changes previously reported in sedentary women. Further research is needed to understand why other metabolic hormones are more robust against low energy availability in exercising men than those in sedentary and exercising women. PMID- 26852784 TI - Characterisation of the inflammatory response in Dupuytren's disease. AB - BACKGROUND: Dupuytren's disease is characterised by fibrotic nodule and cord formation in the palmar aponeurosis. The pathophysiology of the disease is still unknown, although cell stress and subsequent activation of immune mechanisms seems to be crucial. MATERIALS AND METHODS: Surgically obtained tissue and blood samples of 100 Dupuytren patients were processed by immunohistochemistry, flow cytometry, as well as immunoscope analysis. Macroscopically normal aponeurotic tissue served as control. RESULTS: Locally, microvascular alterations and massive infiltration by mononuclear cells (CD3+, CD4 > CD8, CD45RO > CD45RA, S100 protein, CD56, CD68, scarce CD19 and mast cells) forming perivascular clusters were found in DD tissue. Cytokine profiling of fibromatosis tissue-derived T cells showed a Th1/TH17-weighted immune response. Immunoscope analysis revealed a restricted T-cell receptor alpha/beta repertoire pointing to an (auto)antigen driven process. CONCLUSION: The striking accumulation of immune cells, expression of leukocyte adhesion molecules, as well as pro-inflammatory and pro-fibrotic cytokines near markedly narrowed vessels supports the theory that the abnormal proliferation of fibroblasts and production of extracellular matrix proteins in DD seems to be related to immune-mediated microvascular damage. The restricted T cell receptor repertoire of intra-lesional T-cells points to an antigen-driven process. T-cells seem to play an important role in the development of Dupuytren's disease. PMID- 26852786 TI - International service learning in the Dominican Republic: An asynchronous pilot in interprofessional education. AB - Despite the logistical barriers of asynchronous academic calendars, university students in nursing and physical therapy in one academic health centre piloted an international, interprofessional, service learning project in the Dominican Republic. Although the nursing students and physical therapy students were not able to be in-country at the same time, they provided care to a common caseload of traumatic injury patients and those with chronic, debilitating conditions. Interprofessional communication occurred with the development of SBAR (Situation, Background, Assessment, Recommendation) reports from the Team Training curriculum of the Agency for Healthcare Research and Quality. Students learned the depth of physical therapy and the breadth of nursing. The pilot led to a more refined design to pair nursing and PT students, requiring them to communicate via mobile phone regarding results of examinations, and suggestions for follow-up by the nursing students, to ensure continuity of care and a more comprehensive approach to services. PMID- 26852785 TI - Stigma, activism, and well-being among people living with HIV. AB - Evidence demonstrates that HIV stigma undermines the psychological and physical health of people living with HIV (PLWH). Yet, PLWH describe engaging in HIV activism to challenge stigma, and research suggests that individuals may benefit from activism. We examine associations between experiences of HIV stigma and HIV activism, and test whether HIV activists benefit from greater well-being than non activists. Participants include 93 PLWH recruited from drop-in centers, housing programs, and other organizations providing services to PLWH in the Northeastern USA between 2012 and 2013 (mean age = 50 years; 56% Black, 20% White, 18% Other; 61% non-Latino(a), 39% Latino(a); 59% male, 38% female, 3% transgender; 82% heterosexual, 15% sexual minority). Participants completed a cross-sectional written survey. Results of regression analyses suggest that PLWH who experienced greater enacted stigma engaged in greater HIV activism. Anticipated, internalized, and perceived public stigma, however, were unrelated to HIV activism. Moreover, results of a multivariate analysis of variance suggest that HIV activists reported greater social network integration, greater social well being, greater engagement in active coping with discrimination, and greater meaning in life than non-activists. Yet, HIV activists also reported somewhat greater depressive symptoms than non-activists, suggesting that the association between HIV activism and well-being is complex. By differentiating between HIV stigma mechanisms, the current study provides a more nuanced understanding of which experiences of HIV stigma may be associated with HIV activism. It further suggests that engagement in activism may offer benefits to PLWH, while raising the possibility that activists could experience greater depressive symptoms than non-activists. Given the preliminary nature of this study, future research should continue to examine these complex associations between HIV stigma, activism, and well-being among PLWH. As this work continues, PLWH, as well as interventionists and clinicians invested in improving well-being among PLWH, should carefully weigh the benefits and potential costs of activism. PMID- 26852787 TI - Pharmacodynamic considerations in the use of matrix metalloproteinase inhibitors in cancer treatment. AB - INTRODUCTION: Matrix metalloproteinases (MMPs) are classified in the family of zinc-dependent endopeptidases, which can degrade various components of an extracellular matrix and a basement membrane. Studies have demonstrated that MMPs relate to the development of malignant tumors and induce angiogenesis, resulting in the invasion and metastasis of tumor cells. MMPs are highly expressed in malignant tumors and are related to cancer patients' malignant phenotype and poor prognosis. Therefore, blocking the expression or activity of MMPs may be a promising strategy for cancer treatment. AREAS COVERED: This study aimed to explain the MMP structure, regulatory mechanism, and carcinogenic effect; investigate the matrix metalloproteinase-inhibitors (MMPIs) that are currently used in clinical trials for cancer treatment; and summarize the trial results. EXPERT OPINION: Currently, the results of clinical trials that have used MMPIs as anticancer agents are unsatisfactory. However, MMPs remain an attractive target for cancer treatment. For example, development of the specific peptide or antibodies in targeting the hemopexin domain of MMP-2 may be a new therapeutic direction. The design and development of MMPIs that have selectivity will be the primary focus in future studies. PMID- 26852788 TI - Reduction in the severity of early onset severe preeclampsia during gestation may be associated with changes in endothelial cell activation: A pathological case report. AB - Early severe preeclampsia with changes consistent with the Hemolysis elevated liver enzymes low platelet count (HELLP) variant and severe fetal growth restriction rarely resolves prior to delivery. Established clinical disease is preceded by endothelial dysfunction and inflammation. Endothelial activation is reported in vitro to be raised in the presence of necrotic trophoblastic debris which is deported into the maternal circulation in preeclampsia. We report on an early severe preeclamptic patient admitted at 24 weeks gestation. Maternal serum was taken at day 2, 16, 30 of admission and 45 days postpartum. 20% maternal serum or trophoblastic debris from first trimester placental explants that had been cultured with 10% maternal serum was exposed to endothelial cells. Endothelial cell activation was quantified by the cell surface ICAM-1 expression and U937 monocyte adhesion assay. The clinical condition of this patient improved including the blood pressure, liver function, and platelet count by the 3rd day after antihypertensive treatment and remained normal until delivery at 37 weeks. ICAM-1 expression and U937 moncyte adhesion assay of endothelial cells was significantly increased following exposure of the endothelial cells to the maternal serum or trophoblastic debris from placentae treated with maternal serum drawn on day 2. However, ICAM-1 expression and the monocyte adhesion assay were significantly reduced following exposure of endothelial cells to maternal serum or trophoblastic debris from placenta treated with maternal serum drawn on day 16 or 30. Our data suggest unknown factor(s) in the maternal serum triggered endothelial cell activation when the clinical symptoms were present. The improvement in the clinical condition occurred along with the changes in endothelial cell activation. PMID- 26852789 TI - Impact of potato processing on nutrients, phytochemicals, and human health. AB - Potatoes (Solanum tuberosum) are an important global crop that can be transformed into many products impacting several health dimensions ranging from undernutrition, food security and disease prevention to issues of overnutrition including obesity, diabetes, heart disease. Processed potato products are typically categorized as high fat and sodium foods, as well as being classified as a significant source of carbohydrate, in the form of starch. Conversely, potato products are less known for their contribution of key micronutrients (vitamin C, potassium, magnesium), fiber, and phytochemicals (phenolics and carotenoids). More recent insight into the nutritional value of potatoes and the potential of potato phytochemicals to modulate oxidative and inflammatory stress as well as the potential to alter glycemic response has resulted in increased interest in strategies to improve and leverage the nutritional quality of processed potatoes. This review summarizes critical information on nutritional profiles of potatoes and their processed products and describes the state of the science relative to the influence of in-home and common commercial processing on nutritional quality and potential impacts on human health. PMID- 26852791 TI - Application of highly porous materials for simazine removal from aqueous solutions. AB - The removal of simazine from both pure water and solute-bearing well water was studied by adsorption on two solids: zeolite H-Y from the commercial Na form and porous silica tailored by the sol-gel technique. The pH dependence of the amount adsorbed in a closed system at constant total simazine content as well as the apparent isotherms of adsorption was measured in all four cases. The low ion content of natural water suffices to alter the adsorption features in the case of silica, but not with zeolite H-Y. Iteration of the adsorption process onto constant amounts of solid allowed bringing the residual simazine concentration below 0.05 mg/L, the value allowed by Italian laws in wastewaters. PMID- 26852790 TI - "Timing" of arrival and in-hospital mortality in a cohort of patients under anticoagulant therapy presenting to the emergency departments with cerebral hemorrhage: A multicenter chronobiological study in Italy. AB - Therapy with oral anticoagulants (OACs) is a risk factor for cerebral hemorrhage (CH). Although different studies have been undertaken to investigate the timing of the onset of major cardiovascular events, no data exist on temporal patterns of the onset of CH in subjects treated with OACs. The aim of this study is to evaluate the timing of CH in patients treated with OACs. All patients who developed CH under OACs therapy and admitted to 28 Italian Emergency Departments (EDs) between September 2011 and July 2013 were enrolled. Age, sex, time and location of the hemorrhagic lesion, type of the bleeding events (idiopathic or post-traumatic), anticoagulant therapy (warfarin or new oral anticoagulants - NOAs) and time of ED admission (i.e., hour, day, month and season) were recorded. Five hundred and seventeen patients (63.2% male aged 80 +/- 7.9 yrs) with CH were involved. Warfarin was taken by 494 patients (95.6%), and NOAs by 23 (4.4%). In hospital mortality (IHM) was recorded in 208 cases (40.2%). Cosinor analysis showed a peak of CH arrival between 12:00 and 14:00 h both in the whole population (PR 73.9%, p = 0.002) and the male subgroup (PR 65.2%, p = 0.009), whereas females showed an anticipated morning peak between 08:00 and 10:00 h (PR 65.7%, p = 0.008). A further analysis between idiopathic and post-traumatic CH confirmed the presence of a 24 h pattern with a peak between 12:00 and 14:00 h (PR 58.5%, p = 0.019) and between 08:00 and 10:00 h (PR80.1%, p < 0.001) for idiopathic events and post-traumatic hemorrhages, respectively. Moreover, a seasonal winter peak was identified for idiopathic forms (PR 74%, p = 0.035), and a summer peak for post-traumatic forms (PR 77%, p = 0.025). The present study suggests the presence of a temporal pattern of ED arrivals in CH patients treated with OACs. PMID- 26852792 TI - Successful Chemo-Radiotherapy for Primary Anaplastic Large Cell Lymphoma of the Lung: A Case Report and Literature Review. AB - BACKGROUND: Primary anaplastic large cell lymphoma (ALCL) of the lung is an extremely rare disease. This disease is a great challenge for pneumologists due to its nonspecific clinical presentations and radiological findings. Appropriate invasive biopsy and immunohistochemistry are important for diagnosis. There is currently no standard treatment. CASE REPORT: We report a very rare case of primary pulmonary ALCL in a 39-year-old man. The clinical features, imaging, pathological findings, treatment outcomes, and prognosis, are described. Successful treatment outcomes were achieved after 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy followed by involved field radiotherapy of 54 Gy/27f. The patient was disease free after follow-up for 65 months. CONCLUSIONS: Our study found that chemotherapy (such as CHOP) is recognized as the first-line regimen for primary ALCL of the lung. For patients with dyspnea caused by a mass blocking the main bronchus, chemo-radiotherapy may be a reasonable therapeutic option. The prognosis is better for patients with positive ALK staining. CD56(+), age older than 60 years, Ann Arbor stage III or IV, survivin expression, PS>2, and high serum LDH level and IPI scores are the poor prognostic factors of ALCL. PMID- 26852793 TI - Regulation of Arabidopsis MAPKKK18 by ABI1 and SnRK2, components of the ABA signaling pathway. AB - The plant hormone abscisic acid (ABA), a key regulator in many crucial developmental and physiological processes, recruits diverse components into precisely regulated signaling network. We recently discovered that MAPKKK18, an ABA-activated kinase, is regulated by the protein phosphatase type 2C (PP2C) ABI1 and the kinase SnRK2.6, both components of the ABA core signaling pathway. ABI1 acts to inhibit MAPKKK18 kinase activity, but also affects MAPKKK18 protein turnover via the ubiquitin-proteasome pathway. SnRK2.6 kinase also seems to be important for the regulation of MAPKKK18 function. In this review we summarize the mechanisms that are exclusively involved in MAPKKK18 kinase regulation and that ensure specificity in its activation. PMID- 26852794 TI - Unintended consequences of an 'all-clear' diagnosis for potential cancer symptoms: a nested qualitative interview study with primary care patients. AB - BACKGROUND: Nine out of 10 patients undergoing urgent cancer investigations receive an 'all-clear' diagnosis. AIM: A qualitative approach was used to evaluate the impact of investigations that did not result in cancer diagnosis on subsequent symptom attribution and help seeking for recurrent or new possible cancer symptoms. DESIGN AND SETTING: A survey of symptoms, help seeking, and past investigations was sent to 4913 individuals aged >=50 years from four UK general practices. Of 2042 responders, 62 participants were recruited still reporting at least one cancer 'alarm' symptom in a 3-month follow-up survey for a nested in depth interview study (ensuring variation in sociodemographic characteristics). METHOD: Framework analysis was used to examine the in-depth semi-structured interviews and identify themes related to previous health investigations. RESULTS: Interviewees were on average 65 years old, and 90% reported investigations within the previous 2 years. Most often they reported gastrointestinal, urinary, and respiratory symptoms, and 42% had waited >=3 months before help seeking. Reassurance from a previous non-cancer diagnosis explained delays in help seeking even if symptoms persisted or new symptoms developed months or years later. Others were worried about appearing hypochondriacal or that they would not be taken seriously if they returned to the doctor. CONCLUSION: An all-clear diagnosis can influence help seeking for months or even years in case of new or recurrent alarm symptoms. Considering the increasing number of people undergoing investigations and receiving an all-clear, it is paramount to limit unintended consequences by providing appropriate information and support. Specific issues are identified that could be addressed. PMID- 26852796 TI - Performance characteristics of visualising the cervix in symptomatic young females: a review of primary care records in females with and without cervical cancer. AB - BACKGROUND: The current strategy for timely detection of cervical cancer in young females centres on visualising the cervix when females present with gynaecological symptoms, but is based on expert opinion without an evidence base. AIM: To assess visualising the cervix in primary care in young females with gynaecological symptoms. DESIGN AND SETTING: A review of primary care records for females in England aged 20-29 years with cervical cancer (nationwide interview based study) and in the general population (Clinical Practice Research Datalink database). METHOD: From primary care records the proportion of females was identified with gynaecological symptoms who had documented cervical examination in the year before diagnosis (cancers) and in 1-year age bands (general population). Of these, the proportion was identified that was then referred for suspected malignancy. RESULTS: Only 39% of young females with cervical cancer had documented examination at symptomatic presentation. Visualisation resulted in referral for suspected malignancy for 18% of those examined (95% confidence interval = 5% to 40%). Very few (<1.7%) symptomatic females in the general population had documented cervical examination. None were referred for suspected malignancy at the time. CONCLUSION: The sensitivity of cervical examination to detect cancer is very low, highlighting the need for better triage tools for primary care. Until such tools are identified GPs should continue to consider cervical cancer when symptoms persist and the cervix is not obviously abnormal on clinical examination. Further research on additional triage tools such as cervical cytology used as a diagnostic aid is needed urgently. PMID- 26852795 TI - Primary care clinician antibiotic prescribing decisions in consultations for children with RTIs: a qualitative interview study. AB - BACKGROUND: Respiratory tract infections (RTIs) are a major primary care challenge in children because they are common and costly, there is uncertainty regarding their diagnosis, prognosis, and management, and the overuse of antibiotics leads to illness medicalisation and bacterial resistance. AIM: To investigate healthcare professional (HCP) diagnostic and antibiotic prescribing decisions for children with RTIs. DESIGN AND SETTING: Semi-structured interviews conducted with 22 GPs and six nurses. HCPs were recruited from six general practices and one walk-in centre, serving a mix of deprived and affluent areas. METHOD: Interviews were audiorecorded, transcribed, imported into NVivo 9, and analysed thematically. RESULTS: HCPs varied in the symptom and clinical examination findings used to identify children they thought might benefit from antibiotics. Their diagnostic reasoning and assessment of perceived clinical need for antibiotics used a dual process, combining an initial rapid assessment with subsequent detailed deductive reasoning. HCPs reported confidence diagnosing and managing most minor and severe RTIs. However, residual prognostic uncertainty, particularly for the intermediate illness severity group, frequently led to antibiotic prescribing to mitigate the perceived risk of subsequent illness deterioration. Some HCPs perceived a need for more paediatrics training to aid treatment decisions. The study also identified a number of non-clinical factors influencing prescribing. CONCLUSION: Prognostic uncertainty remains an important driver of HCPs' antibiotic prescribing. Experience and training in recognising severe RTIs, together with more evidence to help HCPs identify the children at risk of future illness deterioration, may support HCPs' identification of the children most and least likely to benefit from antibiotics. PMID- 26852798 TI - Improvement of Pharmaceutical Properties of Isoprenoid Compounds through the Formation of Cyclodextrin Pseudorotaxane-Like Supramolecules. AB - The purpose of this study was to design cyclodextrin (CyD)-based pseudorotaxane like supramolecular complexes with various isoprenoid compounds, such as reduced coenzyme Q10 (R-CoQ10), squalene, tocotrienol, and teprenone, and to evaluate their pharmaceutical properties. Squalene, tocotrienol, and teprenone formed precipitates with beta-CyD and gamma-CyD in aqueous solution, whereas R-CoQ10 formed precipitates with gamma-CyD aqueous solution. The results of powder X-ray diffraction and (1)H-NMR analyses indicated that these precipitates are derived from pseudorotaxane-like supramolecular complexes. The photostability of teprenone was markedly improved by complexation with CyDs, especially in the gamma-CyD system. In addition, the dispersion rates of teprenone in the gamma-CyD system were higher than those in the beta-CyD system, compared with the corresponding physical mixtures. In conclusion, pharmaceutical properties such as photostability and dispersion rates of isoprenoid compounds were improved by the formation of pseudorotaxane-like supramolecular complexes with beta-CyD and/or gamma-CyD. PMID- 26852797 TI - 'I'm fishing really'--inflammatory marker testing in primary care: a qualitative study. AB - BACKGROUND: Inflammatory markers can be helpful as part of the diagnostic workup for specific diseases or for monitoring disease activity. A third use is as a screening and/or triage tool to differentiate between the presence or absence of disease. Most research into inflammatory markers looks at diagnosis of specific diseases and comes from secondary care. Qualitative studies to explore when and why clinicians use these tests in primary care are lacking. AIM: To identify clinicians' approaches to inflammatory marker testing in primary care. DESIGN AND SETTING: Qualitative study with 26 GPs and nurse practitioners. METHOD: Interviews were conducted using a semi-structured topic guide. Clinicians reviewed recent cases of inflammatory marker testing in their pathology inbox. Interviews were audiorecorded and transcribed. Qualitative analysis was conducted by two of the authors. RESULTS: Clinicians are uncertain about the appropriate use of inflammatory markers and differ in their approach to testing patients with undifferentiated symptoms. Normal or significantly elevated inflammatory markers are seen as helpful, but mildly raised inflammatory markers in the context of non specific symptoms are difficult to interpret. Clinicians describe a tension between not wanting to 'miss anything' and, on the other hand, being wary of picking up borderline abnormalities that can lead to cascades of further tests. Diagnostic uncertainty is a common reason for inflammatory marker testing, with the aim to reassure; however, paradoxically, inconclusive results can generate a cycle of uncertainty and anxiety. CONCLUSION: Further research is needed to define when inflammatory marker testing is useful in primary care and how to interpret results. PMID- 26852799 TI - Thermoelectric Power in Bilayer Graphene Device with Ionic Liquid Gating. AB - The quest for materials showing large thermoelectric power has long been one of the important subjects in material science and technology. Such materials have great potential for thermoelectric cooling and also high figure of merit ZT thermoelectric applications. We have fabricated bilayer graphene devices with ionic-liquid gating in order to tune its band gap via application of a perpendicular electric field on a bilayer graphene. By keeping the Fermi level at charge neutral point during the cool-down, we found that the charge puddles effect can be greatly reduced and thus largely improve the transport properties at low T in graphene-based devices using ionic liquid gating. At (Vig, Vbg) = (-1 V, +23 V), a band gap of about 36.6 +/- 3 meV forms, and a nearly 40% enhancement of thermoelectric power at T = 120 K is clearly observed. Our works demonstrate the feasibility of band gap tuning in a bilayer graphene using ionic liquid gating. We also remark on the significant influence of the charge puddles effect in ionic-liquid-based devices. PMID- 26852801 TI - Probing of multiple magnetic responses in magnetic inductors using atomic force microscopy. AB - Even though nanoscale analysis of magnetic properties is of significant interest, probing methods are relatively less developed compared to the significance of the technique, which has multiple potential applications. Here, we demonstrate an approach for probing various magnetic properties associated with eddy current, coil current and magnetic domains in magnetic inductors using multidimensional magnetic force microscopy (MMFM). The MMFM images provide combined magnetic responses from the three different origins, however, each contribution to the MMFM response can be differentiated through analysis based on the bias dependence of the response. In particular, the bias dependent MMFM images show locally different eddy current behavior with values dependent on the type of materials that comprise the MI. This approach for probing magnetic responses can be further extended to the analysis of local physical features. PMID- 26852800 TI - Salinity altered root distribution and increased diversity of bacterial communities in the rhizosphere soil of Jerusalem artichoke. AB - The interaction between roots and bacterial communities in halophytic species is poorly understood. Here, we used Jerusalem artichoke cultivar Nanyu 1 (NY-1) to characterise root distribution patterns and determine diversity and abundance of bacteria in the rhizosphere soil under variable salinity. Root growth was not inhibited within the salinity range 1.2 to 1.9 g salt/kg, but roots were mainly confined to 0-20 cm soil layer vertically and 0-30 cm horizontally from the plant centre. Root concentrations of K(+), Na(+), Mg(2+) and particularly Ca(2+) were relatively high under salinity stress. High salinity stress decreased soil invertase and catalase activity. Using a next-generation, Illumina-based sequencing approach, we determined higher diversity of bacteria in the rhizosphere soil at high than low salinity. More than 15,500 valid reads were obtained, and Proteobacteria, Acidobacteria, Bacteroidetes and Actinobacteria predominated in all samples, accounting for >80% of the reads. On a genus level, 636 genera were common to the low and high salinity treatments at 0-5 cm and 5-10 cm depth. The abundance of Steroidobacter and Sphingomonas was significantly decreased by increasing salinity. Higher Shannon and Chao 1 indices with increasing severity of salt stress indicated that high salt stress increased diversity in the bacterial communities. PMID- 26852802 TI - First passage time distribution in heterogeneity controlled kinetics: going beyond the mean first passage time. AB - The first passage is a generic concept for quantifying when a random quantity such as the position of a diffusing molecule or the value of a stock crosses a preset threshold (target) for the first time. The last decade saw an enlightening series of new results focusing mostly on the so-called mean and global first passage time (MFPT and GFPT, respectively) of such processes. Here we push the understanding of first passage processes one step further. For a simple heterogeneous system we derive rigorously the complete distribution of first passage times (FPTs). Our results demonstrate that the typical FPT significantly differs from the MFPT, which corresponds to the long time behaviour of the FPT distribution. Conversely, the short time behaviour is shown to correspond to trajectories connecting directly from the initial value to the target. Remarkably, we reveal a previously overlooked third characteristic time scale of the first passage dynamics mirroring brief excursion away from the target. PMID- 26852803 TI - Experimental control of transport resonances in a coherent quantum rocking ratchet. AB - The ratchet phenomenon is a means to get directed transport without net forces. Originally conceived to rectify stochastic motion and describe operational principles of biological motors, the ratchet effect can be used to achieve controllable coherent quantum transport. This transport is an ingredient of several perspective quantum devices including atomic chips. Here we examine coherent transport of ultra-cold atoms in a rocking quantum ratchet. This is realized by loading a rubidium atomic Bose-Einstein condensate into a periodic optical potential subjected to a biharmonic temporal drive. The achieved long time coherence allows us to resolve resonance enhancement of the atom transport induced by avoided crossings in the Floquet spectrum of the system. By tuning the strength of the temporal modulations, we observe a bifurcation of a single resonance into a doublet. Our measurements reveal the role of interactions among Floquet eigenstates for quantum ratchet transport. PMID- 26852804 TI - Prostaglandins E2 signal mediated by receptor subtype EP2 promotes IgE production in vivo and contributes to asthma development. AB - Prostaglandins E2 (PGE2) has been shown to enhance IgE production by B cells in vitro. The physiological and pathological relevance of this phenomenon and the underlying molecular mechanism, however, remain to be elucidated. B cells from wild type and EP2-deficient mice were compared in culture for their responses to PGE2 in terms of IgE class switching and production. Ovalbumin (OVA)-induced asthma models were used to evaluate the impact of EP2-deficiency on IgE responses and the development of asthma. PGE2 promoted IgE class switching, generation of IgE(+) cells and secretion of IgE by B cells stimulated with LPS+IL4. These effects were much attenuated as a consequence of EP2 deficiency. Consistent with the in vitro data, EP2-deficient mice showed a markedly suppressed IgE antibody response and developed less pronounced airway inflammation in the OVA-induced asthma model. Mechanistic studies demonstrated that PGE2, in an EP2-depedent manner, enhanced STAT6 activation induced by IL-4, thereby promoting the expression of IgE germline and post switch transcripts and the transcription of activation-induced cytidine deaminase (AID). Collectively, these data support an important regulatory role of the PGE2-EP2-STAT6 signaling pathway in IgE response and allergic diseases. PMID- 26852807 TI - Microbial genetics: Dual RNA-seq for host-pathogen transcriptomics. PMID- 26852805 TI - Theranostic Nanoseeds for Efficacious Internal Radiation Therapy of Unresectable Solid Tumors. AB - Malignant tumors are considered "unresectable" if they are adhere to vital structures or the surgery would cause irreversible damages to the patients. Though a variety of cytotoxic drugs and radiation therapies are currently available in clinical practice to treat such tumor masses, these therapeutic modalities are always associated with substantial side effects. Here, we report an injectable nanoparticle-based internal radiation source that potentially offers more efficacious treatment of unresectable solid tumors without significant adverse side effects. Using a highly efficient incorporation procedure, palladium-103, a brachytherapy radioisotope in clinical practice, was coated to monodispersed hollow gold nanoparticles with a diameter about 120 nm, to form (103)Pd@Au nanoseeds. The therapeutic efficacy of (103)Pd@Au nanoseeds were assessed when intratumorally injected into a prostate cancer xenograft model. Five weeks after a single-dose treatment, a significant tumor burden reduction (>80%) was observed without noticeable side effects on the liver, spleen and other organs. Impressively, >95% nanoseeds were retained inside the tumors as monitored by Single Photon Emission Computed Tomography (SPECT) with the gamma emissions of (103)Pd. These findings show that this nanoseed-based brachytherapy has the potential to provide a theranostic solution to unresectable solid tumors. PMID- 26852808 TI - Epigenomics: Custom remodelling. PMID- 26852806 TI - Microfluidic high-throughput selection of microalgal strains with superior photosynthetic productivity using competitive phototaxis. AB - Microalgae possess great potential as a source of sustainable energy, but the intrinsic inefficiency of photosynthesis is a major challenge to realize this potential. Photosynthetic organisms evolved phototaxis to find optimal light condition for photosynthesis. Here we report a microfluidic screening using competitive phototaxis of the model alga, Chlamydomonas reinhardtii, for rapid isolation of strains with improved photosynthetic efficiencies. We demonstrated strong relationship between phototaxis and photosynthetic efficiency by quantitative analysis of phototactic response at the single-cell level using a microfluidic system. Based on this positive relationship, we enriched the strains with improved photosynthetic efficiency by isolating cells showing fast phototactic responses from a mixture of 10,000 mutants, thereby greatly improving selection efficiency over 8 fold. Among 147 strains isolated after screening, 94.6% showed improved photoautotrophic growth over the parental strain. Two mutants showed much improved performances with up to 1.9- and 8.1-fold increases in photoautotrophic cell growth and lipid production, respectively, a substantial improvement over previous approaches. We identified candidate genes that might be responsible for fast phototactic response and improved photosynthesis, which can be useful target for further strain engineering. Our approach provides a powerful screening tool for rapid improvement of microalgal strains to enhance photosynthetic productivity. PMID- 26852809 TI - The effect of reduced sodium chloride content on the microbiological and biochemical properties of a soft surface-ripened cheese. AB - Many health authorities have targeted salt reduction in food products as a means to reduce dietary sodium intake due to the harmful effects associated with its excessive consumption. In the present work, we evaluated the effect of reducing sodium chloride (NaCl) content on the microbiological and biochemical characteristics of an experimental surface-ripened cheese. A control cheese (1.8% NaCl) and a cheese with a reduced NaCl content (1.3% NaCl) were sampled weekly over a period of 27d. Reducing NaCl content induced microbial perturbations such as the lesser development of the yeast Debaryomyces hansenii and the greater development of the gram-negative bacterium Hafnia alvei. This was accompanied by changes in proteolytic kinetics and in profiles of volatile aroma compounds and biogenic amine production. Finally, the development of the spoilage microorganism Pseudomonas fragi was significantly higher in the cheese with a reduced salt content. PMID- 26852810 TI - Comparative anatomy of the middle ear ossicles of extant hominids--Introducing a geometric morphometric protocol. AB - The presence of three interconnected auditory ossicles in the middle ear is a defining characteristic of mammals, and aspects of ossicle morphology are related to hearing sensitivity. However, analysis and comparison of ossicles are complicated by their minute size and complex three-dimensional shapes. Here we introduce a geometric morphometric measurement protocol for 3D shape analysis based on landmarks and semilandmarks obtained from MUCT images and apply it to ossicles of extant hominids (great apes and humans). We show that the protocol is reliable and reproducible over a range of voxel resolutions, and captures even subtle shape differences. Using this approach it is possible to distinguish the hominid taxa by mean shapes of their malleus and incus (p < 0.01). The stapes appears less diagnostic, although this may in part be related to the small sample size available. Using ancestral state estimation, we show that, within hominids, Homo sapiens is derived with respect to its malleus (short manubrium, long corpus, head anterior-posterior flattened, articular facet shape), incus (wide intercrural curvature, long incudal processes, articular facet shape) and stapes (high stapes with kidney-shaped footplate). H. sapiens also shows a number of plesiomorphic shape traits whereas Gorilla and Pan possess a number of autapomorphic characteristics. The Pongo ossicles appear to be close to the plesiomorphic hominid condition. The malleus shows little difference in size among hominids, and allometry is thus of little importance. In contrast, the incus and stapes are more variable in size, and their shape is more strongly related to size differences. Although the form-function relationships in the middle ear are not fully understood, some aspects of ossicle morphology suggest that interspecific differences in hearing capacities are present among hominids. Finally, the results of this study provide a comparative framework for morphometric studies analyzing ossicles of extinct hominids, with a bearing on taxonomy, phylogeny and auditory function. PMID- 26852811 TI - Cranial base topology and basic trends in the facial evolution of Homo. AB - Facial prognathism and projection are important characteristics in human evolution but their three-dimensional (3D) architectonic relationships to basicranial morphology are not clear. We used geometric morphometrics and measured 51 3D-landmarks in a comparative sample of modern humans (N = 78) and fossil Pleistocene hominins (N = 10) to investigate the spatial features of covariation between basicranial and facial elements. The study reveals complex morphological integration patterns in craniofacial evolution of Middle and Late Pleistocene hominins. A downwards-orientated cranial base correlates with alveolar maxillary prognathism, relatively larger faces, and relatively larger distances between the anterior cranial base and the frontal bone (projection). This upper facial projection correlates with increased overall relative size of the maxillary alveolar process. Vertical facial height is associated with tall nasal cavities and is accommodated by an elevated anterior cranial base, possibly because of relations between the cribriform and the nasal cavity in relation to body size and energetics. Variation in upper- and mid-facial projection can further be produced by basicranial topology in which the midline base and nasal cavity are shifted anteriorly relative to retracted lateral parts of the base and the face. The zygomatics and the middle cranial fossae act together as bilateral vertical systems that are either projected or retracted relative to the midline facial elements, causing either midfacial flatness or midfacial projection correspondingly. We propose that facial flatness and facial projection reflect classical principles of craniofacial growth counterparts, while facial orientation relative to the basicranium as well as facial proportions reflect the complex interplay of head-body integration in the light of encephalization and body size decrease in Middle to Late Pleistocene hominin evolution. Developmental and evolutionary patterns of integration may only partially overlap morphologically, and traditional concepts taken from research on two-dimensional (2D) lateral X-rays and sections have led to oversimplified and overly mechanistic models of basicranial evolution. PMID- 26852812 TI - The Uluzzian technology of Grotta di Fumane and its implication for reconstructing cultural dynamics in the Middle-Upper Palaeolithic transition of Western Eurasia. AB - From the intricate ensemble of evidence related to the Middle-Upper Palaeolithic transition and the presumed first spread of anatomically modern humans in Europe, the Uluzzian has attracted major attention in the past few years. Although the Uluzzian has been viewed as a supposed product of modern humans settling in Mediterranean Europe, the techno-cultural complex has been the subject of few investigations aiming to clarify its chronology, bone industry, and settlement dynamics. Further, little is known of its technological structure. This article presents the results of an extensive study of the lithic and bone technologies from assemblages recovered at Fumane Cave in the north of Italy. Results confirm that the Uluzzian is a flake-dominated industry that brings together a set of technological innovations. The Levallois is the most used method in the initial phase, which is replaced by more varied flaking procedures and an increase in bladelets and flake-blades. Sidescrapers and points also represent a Mousterian feature in the initial phase, while splintered pieces, backed knives and other Upper Palaeolithic tools increase in the later phase. Our results suggest that the Uluzzian is rooted in the Mousterian lithic technological context and cannot be viewed as a proxy for anatomically modern humans, the carriers of the abrupt cultural changes related to the Aurignacian. PMID- 26852813 TI - Virtual ancestor reconstruction: Revealing the ancestor of modern humans and Neandertals. AB - The timing and geographic origin of the common ancestor of modern humans and Neandertals remain controversial. A poor Pleistocene hominin fossil record and the evolutionary complexities introduced by dispersals and regionalisation of lineages have fuelled taxonomic uncertainty, while new ancient genomic data have raised completely new questions. Here, we use maximum likelihood and 3D geometric morphometric methods to predict possible morphologies of the last common ancestor of modern humans and Neandertals from a simplified, fully resolved phylogeny. We describe the fully rendered 3D shapes of the predicted ancestors of humans and Neandertals, and assess their similarity to individual fossils or populations of fossils of Pleistocene age. Our results support models of an Afro-European ancestral population in the Middle Pleistocene (Homo heidelbergensis sensu lato) and further predict an African origin for this ancestral population. PMID- 26852814 TI - Middle Palaeolithic toolstone procurement behaviors at Lusakert Cave 1, Hrazdan valley, Armenia. AB - Strategies employed by Middle Palaeolithic hominins to acquire lithic raw materials often play key roles in assessing their movements through the landscape, relationships with neighboring groups, and cognitive abilities. It has been argued that a dependence on local resources is a widespread characteristic of the Middle Palaeolithic, but how such behaviors were manifested on the landscape remains unclear. Does an abundance of local toolstone reflect frequent encounters with different outcrops while foraging, or was a particular outcrop favored and preferentially quarried? This study examines such behaviors at a finer geospatial scale than is usually possible, allowing us to investigate hominin movements through the landscape surrounding Lusakert Cave 1 in Armenia. Using our newly developed approach to obsidian magnetic characterization, we test a series of hypotheses regarding the locations where hominins procured toolstone from a volcanic complex adjacent to the site. Our goal is to establish whether the cave's occupants procured local obsidian from preferred outcrops or quarries, secondary deposits of obsidian nodules along a river, or a variety of exposures as encountered while moving through the river valley or across the wider volcanic landscape during the course of foraging activities. As we demonstrate here, it is not the case that one particular outcrop or deposit attracted the cave occupants during the studied time intervals. Nor did they acquire obsidian at random across the landscape. Instead, our analyses support the hypothesis that these hominins collected obsidian from outcrops and exposures throughout the adjacent river valley, reflecting the spatial scale of their day-to-day foraging activities. The coincidence of such behaviors within the resource-rich river valley suggests efficient exploitation of a diverse biome during a time interval immediately preceding the Middle to Upper Palaeolithic "transition," the nature and timing of which has yet to be determined for the region. PMID- 26852815 TI - The pattern of emergence of a Middle Stone Age tradition at Gademotta and Kulkuletti (Ethiopia) through convergent tool and point technologies. AB - The Gademotta and Kulkuletti site complex, located in the central part of the Main Ethiopian Rift, is known to be one of the richest early Middle Stone Age (MSA) sequences in East Africa. The technological assessment of three main sites provides evidence of major changes in the production of convergent tools over a period from before 280 ka (thousands of years ago) to ca. 100 ka. Important diachronic changes are identified in the manufacturing process of convergent tools, by shaping or retouching of predetermined points, and in the core reduction process that produced the corresponding blanks. These are: 1) the development of specific Levallois methods for the production of points (classical Levallois point production and Nubian type 1 core reduction); and 2) the shift from uni-bifacial invasive shaping of convergent tools to localized slight retouch of predetermined points. These technological changes in convergent tool production reveal the gradual emergence of a new set of technological behaviors that can be considered specific to the MSA. While the eastern African MSA is often considered as stable over time with minimal innovation, our results provide an insight into local behavioral mechanisms that have given rise to changes in technological systems during the early MSA. PMID- 26852816 TI - Astragalar and calcaneal morphology of the middle Eocene primate Anchomomys frontanyensis (Anchomomyini): Implications for early primate evolution. AB - Astragali and calcanei of Anchomomys frontanyensis, a small adapiform from the middle Eocene of Sant Jaume de Frontanya (Southern Pyrenean basins, northeastern Spain) are described in detail. Though these bones have been known for some time, they have never been carefully analyzed in a context that is comprehensively comparative, quantitative, considers sample variation (astragalus n = 4; calcaneus n = 16), and assesses the phylogenetic significance of the material in an explicit cladistic context, as we do here. Though these bones are isolated, regression analyses provide the first formal statistical support for attribution to A. frontanyensis. The astragalus presents features similar to those of the small stem strepsirrhine Djebelemur from the middle Eocene of Tunisia, while the calcaneus more closely resembles those of the basal omomyiform Teilhardina. The new phylogenetic analyses that include Anchomomys' postcranial and dental data recover anchomomyins outside of the adapiform clade, and closer to djebelemurids, azibiids, and crown strepsirrhines. The small size of A. frontanyensis allows comparison of similarly small adapiforms and omomyiforms (haplorhines) such that observed variation has more straightforward implications for function. Previous studies have demonstrated that distal calcaneal elongation is reflective of leaping proclivity when effects of body mass are appropriately accounted for; in this context, A. frontanyensis has calcaneal elongation suggesting a higher degree of leaping specialization than other adapiforms and even some early omomyiforms. Moreover, comparison to a similarly-sized early adapiform from India, Marcgodinotius (which shows no calcaneal elongation) confirms that high distal calcaneal elongation in A. frontanyensis cannot be simply explained by allometric effects of small size compared to larger adapiform taxa. This pattern is consistent with the idea that significant distal calcaneal elongation evolved at least twice in early euprimates, and that early primate niche space frequently included demands for increased leaping specialization. PMID- 26852817 TI - New endemic platyrrhine humerus from Haiti and the evolution of the Greater Antillean platyrrhines. AB - Much debate surrounds the phylogenetic affinities of the endemic Greater Antillean platyrrhines. Thus far, most phylogenetic analyses have been constructed and tested using craniodental characters. We add to this dialog by considering how features of the distal humerus support or refute existing hypotheses for the origins of fossil Caribbean primates, utilizing three dimensional geometric morphometric data in combination with character based cladistic analyses. We also add to the sample of fossil platyrrhine humeri with the description of UF 114718, a new distal humerus from Haiti. We reconstruct UF 114718 to be a generalized, arboreal quadruped attributed to the species Insulacebus toussantiana. Our results from phylogenetic analyses lend some support to the idea that some Greater Antillean fossil taxa including Xenothrix mcgregori, Antillothrix bernensis, and Insulacebus toussaintiana could form a monophyletic clade that is sister to either extant Platyrrhini or basal pitheciids. Based on the distal humeral data, we reconstruct the earliest ancestral platyrrhine to be a generalized, arboreal quadruped that potentially emphasized pronated arm postures during locomotion and may have engaged in some limited climbing, most similar in shape to early anthropoids and some of the earliest Antillean forms. However, aspects of shape and standard qualitative characters relating to the distal humerus seem to be variable and prone to both homoplasy and reversals; thus these results must be interpreted cautiously and (where possible) within the context provided by other parts of the skeleton. PMID- 26852818 TI - First hominin fossils from Milner Hall, Sterkfontein, South Africa. PMID- 26852819 TI - Steroidal Saponins in Oat Bran. AB - Saponins are one type of widespread defense compound in the plant kingdom and have been exploited for the production of lead compounds with diverse pharmacological properties in drug discovery. Oats contain two unique steroidal saponins, avenacoside A, 1, and avenacoside B, 2. However, the chemical composition, the levels of these saponins in commercial oat products, and their health effects are still largely unknown. In this study, we directly purified 5 steroidal saponins (1-5) from a methanol extract of oat bran, characterized their structures by analyzing their MS and NMR spectra, and also tentatively identified 11 steroidal saponins (6-16) on the basis of their tandem mass spectra (MS(n), n = 2-3). Among the five purified saponins, 5 is a new compound and 4 is purified from oats for the first time. Using HPLC-MS techniques, a complete profile of oat steroidal saponins was determined, and the contents of the two primary steroidal saponins, 1 and 2, were quantitated in 15 different commercial oat products. The total levels of these two saponins vary from 49.6 to 443.0 mg/kg, and oat bran or oatmeal has higher levels of these two saponins than cold oat cereal. Furthermore, our results on the inhibitory effects of 1 and 2 against the growth of human colon cancer cells HCT-116 and HT-29 showed that both had weak activity, with 2 being more active than 1. PMID- 26852820 TI - The therapeutic potential of renin angiotensin aldosterone system (RAAS) in chronic pain: from preclinical studies to clinical trials. AB - The prevalence rate of chronic pain is 15% to 25% in adults while the therapeutic arsenal is still insufficient, especially in relieving neuropathic pain. Peripheral pain transmission is conducted by the small Adelta and C sensory nerve fibres. They express elements from the renin-angiotensin-aldosterone system (RAAS), a well-known blood pressure regulator. Recently, studies have demonstrated the role of angiotensin II, its derivatives and aldosterone in the modulation of pain perception, by interacting with receptors expressed by sensory nerve fibres or through the central nervous system. Here, we assess the effects of RAAS modulators in the conduction of pain with molecular, preclinical and clinical approaches, in normal or pathological conditions. Currently, some clinical studies have been carried out on the pain-relieving effect of RAAS modulators and suggest their potential in the management of chronic, inflammatory or neuropathic pain. PMID- 26852821 TI - Thioetherification via Photoredox/Nickel Dual Catalysis. AB - Hypervalent alkylsilicates represent new and readily accessible precursors for the generation of alkyl radicals under photoredox conditions. Alkyl radicals generated from such silicates serve as effective hydrogen atom abstractors from thiols, furnishing thiyl radicals. The reactive sulfur species generated in this manner can be funneled into a nickel-mediated cross-coupling cycle employing aromatic bromides to furnish thioethers. The serendipitous discovery of this reaction and its utilization for the thioetherification of various aryl and heteroaryl bromides with a diverse array of thiols is described. The S-H selective H atom abstraction event enables a wide range of functional groups, including those bearing protic moieties, to be tolerated. PMID- 26852822 TI - Locating AED Enabled Medical Drones to Enhance Cardiac Arrest Response Times. AB - BACKGROUND: Out-of-hospital cardiac arrest (OOHCA) is prevalent in the United States. Each year between 180,000 and 400,000 people die due to cardiac arrest. The automated external defibrillator (AED) has greatly enhanced survival rates for OOHCA. However, one of the important components of successful cardiac arrest treatment is emergency medical services (EMS) response time (i.e., the time from EMS "wheels rolling" until arrival at the OOHCA scene). Unmanned Aerial Vehicles (UAV) have regularly been used for remote sensing and aerial imagery collection, but there are new opportunities to use drones for medical emergencies. OBJECTIVE: The purpose of this study is to develop a geographic approach to the placement of a network of medical drones, equipped with an automated external defibrillator, designed to minimize travel time to victims of out-of-hospital cardiac arrest. Our goal was to have one drone on scene within one minute for at least 90% of demand for AED shock therapy, while minimizing implementation costs. METHODS: In our study, the current estimated travel times were evaluated in Salt Lake County using geographical information systems (GIS) and compared to the estimated travel times of a network of AED enabled medical drones. We employed a location model, the Maximum Coverage Location Problem (MCLP), to determine the best configuration of drones to increase service coverage within one minute. RESULTS: We found that, using traditional vehicles, only 4.3% of the demand can be reached (travel time) within one minute utilizing current EMS agency locations, while 96.4% of demand can be reached within five minutes using current EMS vehicles and facility locations. Analyses show that using existing EMS stations to launch drones resulted in 80.1% of cardiac arrest demand being reached within one minute Allowing new sites to launch drones resulted in 90.3% of demand being reached within one minute. Finally, using existing EMS and new sites resulted in 90.3% of demand being reached while greatly reducing estimated overall costs. CONCLUSION: Although there are still many factors to consider, drone networks show potential to greatly reduce life-saving equipment travel times for victims of cardiac arrest. PMID- 26852823 TI - Computerized Tomography Measures During and After Artificial Lengthening of the Vocal Tract in Subjects With Voice Disorders. AB - PURPOSE: The present study aimed to observe the effect of two types of tubes on vocal tract bidimensional and tridimensional images. METHODS: Ten participants with hyperfunctional dysphonia were included. Computerized tomography was performed during production of sustained [a:], followed by sustained phonation into a drinking straw, and then repetition of sustained [a:]. A similar procedure was performed with a stirring straw after 15 minutes of vocal rest. Anatomic distances and area measures were obtained from computerized tomography midsagittal and transversal images. Vocal tract total volume was also calculated. RESULTS: During tube phonation, increases were measured in the vertical length of the vocal tract, oropharyngeal area, hypopharyngeal area, outlet of the epilaryngeal tube, and inlet to the lower pharynx. Also, the larynx was lower, and more closure was noted between the velum and the nasal passage. CONCLUSION: Tube phonation causes an increased total vocal tract volume, mostly because of the increased cross-sectional areas in the pharyngeal region. This change is more prominent when the tube offers more airflow resistance (stirring straw) compared with less airflow resistance (drinking straw). Based on our data and previous studies, it seems that vocal tract changes are not dependent on the voice condition (vocally trained, untrained, or disordered voices), but on the exercise itself and the type of instructions given to subjects. Tube phonation is a good option to reach therapeutic goals (eg, wide pharynx and low larynx) without giving biomechanical instructions, but only asking patients to feel easy voice and vibratory sensations. PMID- 26852824 TI - Malignant peripheral nerve sheath tumor of the lower labial mucosa: case report and literature review. AB - Malignant peripheral nerve sheath tumor (MPNST) is an uncommon soft tissue sarcoma with a predilection for the extremities and trunk of adults, rarely occurring in the oral cavity. To date, 10 cases of MPNSTs affecting the lower labial mucosa have been reported in the English language literature. We describe an additional case of MPNST in the lower labial mucosa of a 67-year-old male patient, who exhibited a painful swelling with a history of 4 months of evolution. Microscopic examination showed dense plexiform fascicles of spindle cells with wavy atypical nuclei. Mitotic figures and nuclear pleomorphism were evident. Immunohistochemical analysis of tumor cells revealed positivity for S 100 protein, CD56, CD34, and neuron-specific enolase but was negative for neurofilament protein, glut-1, claudin-1, desmin, and smooth muscle actin. Ki-67 labeling was 20%. The final diagnosis was MPNST. The lesion was surgically removed with wide margins, with no signs of recurrence after 4 years of follow up. PMID- 26852825 TI - Clinicopathologic and immunohistochemical features of five new cases of solitary fibrous tumor of the oral cavity. AB - OBJECTIVE: To describe the clinicopathologic and immunohistochemical features of five cases of oral solitary fibrous tumor. STUDY DESIGN: Clinical data were collected from charts of two oral pathology laboratories of Latin America. All cases were evaluated by conventional hematoxylin and eosin staining and an extended immunohistochemical panel comprising vimentin, CD34, CD99, bcl-2, HHF 35, smooth muscle actin, calponin, S-100 protein, h-caldesmon, and Ki-67. RESULTS: The study included 1 male (20%) and 4 female (80%) patients, with a median age of 43 years. The most common affected site was the buccal mucosa (40%). Tumors were characterized by proliferation of spindled and ovoid cells in a variably vascular and collagenized stroma. All tumors were positive for vimentin, CD34, bcl-2, and CD99. Recurrence was not observed after complete surgical enucleation. CONCLUSIONS: Oral solitary fibrous tumors usually appear as well-delimited submucous nodules with a firm-rubbery consistency and covered by intact mucosa. Immunoreactivity for CD34, bcl-2, and CD-99 is helpful to confirm the diagnosis. PMID- 26852826 TI - Longitudinal study of preterm and full-term infants: High-density EEG analyses of cortical activity in response to visual motion. AB - Electroencephalogram (EEG) was used to investigate brain electrical activity of full-term and preterm infants at 4 and 12 months of age as a functional response mechanism to structured optic flow and random visual motion. EEG data were recorded with an array of 128-channel sensors. Visual evoked potentials (VEPs) and temporal spectral evolution (TSE, time-dependent amplitude changes) were analysed. VEP results showed a significant improvement in full-term infants' latencies with age for forwards and reversed optic flow but not random visual motion. Full-term infants at 12 months significantly differentiated between the motion conditions, with the shortest latency observed for forwards optic flow and the longest latency for random visual motion, while preterm infants did not improve their latencies with age, nor were they able to differentiate between the motion conditions at 12 months. Differences in induced activities were also observed where comparisons between TSEs of the motion conditions and a static non flow pattern showed desynchronised theta-band activity in both full-term and preterm infants, with synchronised alpha-beta band activity observed only in the full-term infants at 12 months. Full-term infants at 12 months with a substantial amount of self-produced locomotor experience and neural maturation coupled with faster oscillating cell assemblies, rely on the perception of structured optic flow to move around efficiently in the environment. The poorer responses in the preterm infants could be related to impairment of the dorsal visual stream specialized in the processing of visual motion. PMID- 26852827 TI - A new look at the shoulder anterior capsuloligamentous complex complementing the insertion of the subscapularis tendon-Anatomical, histological and ultrasound studies of the lesser tuberosity enthesis. AB - PURPOSE: The aim of this study was to examine the relation between the anterior capsuloligamentous complex (ACLC - recognized as a single structure composed of the anterior capsule and its ligaments: medial glenohumeral ligament and anterior bundle of inferior glenohumeral ligament) and the subscapularis tendon with their footprints on the lesser tuberosity. METHODS: In this study, 19 fresh cadaveric shoulder specimens were examined: 13 in morphometric measurements and 6 were examined in a histological study. The subscapularis tendon and the ACLC were dissected until their insertion onto lesser tuberosity. Measurements of both dissected structures and their footprints on the lesser tuberosity were taken with a standard caliper. Six shoulders for histological examination were dissected without separation of the subscapularis tendon from the ACLC and longitudinal and transverse section samples were taken. Additionally, two of these six shoulders underwent ultrasound assessment before final sample preparation. RESULTS: Two well-isolated structures were clearly identifiable: muscle with its tendinous chords and the ACLC, forming together the anterior wall of the joint. The ACLC insertion complemented the tendon insertion - superiorly the thickest part of the tendon stayed in contact with the thinnest part of the ACLC and inferiorly the relation was opposite - the ACLC insertion reached its maximum transverse length. This reciprocal relation was similar to superior and posterior rotator cuff tendon-capsule complex. The footprint on the lesser tuberosity, being purely fibrocartilage enthesis, was composed in 45% of the ACLC insertion. Also the fibers run of the tendon and the ACLC were different: histologic assessment confirmed the tight fusion of the tendon and the ACLC, though those two layers were easily identified as their fibers never mixed. CLINICAL RELEVANCE: Better understanding of the anterior shoulder compartment anatomy simplifies an understanding of some arthroscopic procedures. The shape of the footprint, an importance of a broad superior part of the subscapularis tendon and its relation to the ACLC could be an anatomic proof and explanation for already existing surgical activities: subscapularis release and repair and soft tissue or bony procedures (Latarjet) in anterior shoulder instability. We declare that the experiments comply with the current law of the country in which they were performed (i.e. Polish law). PMID- 26852828 TI - Is extracorporeal treatment useful for managing severe baclofen poisoning? - The debate is still open. PMID- 26852829 TI - Hierarchical porous microspheres of the Co3O4@graphene with enhanced electrocatalytic performance for electrochemical biosensors. AB - The integration of organic and inorganic building blocks into hierarchical porous architectures makes potentially desirable electrocatalytic materials in many electrochemical applications due to their combination of attractive qualities of dissimilar components and well-constructed charge transfer pathways. Herein, we demonstrate the preparation of the hierarchical porous Co3O4@graphene (Co3O4@G) microspheres by one-step hydrothermal method to achieve high electrocatalytic performance for enzyme-free biosensor applications. The obtained Co3O4@G microspheres are consisted of the interconnected networks of Co3O4 and graphene sheets, and thus provide large accessible active sites through porous structure, while graphene sheets offer continuous electron pathways for efficient electrocatalytic reaction of Co3O4. These structural merits with synergy effect of Co3O4 and graphene lead to a high performance of enzyme-free detection for glucose: high sensitivity, good selectivity, and remarkable stability. PMID- 26852830 TI - Label-free femtomolar cancer biomarker detection in human serum using graphene coated surface plasmon resonance chips. AB - Sensitive and selective detection of cancer biomarkers is vital for the successful diagnosis of early stage cancer and follow-up treatment. Surface Plasmon Resonance (SPR) in combination with different amplification strategies is one of the analytical approaches allowing the screening of protein biomarkers in serum. Here we describe the development of a point-of-care sensor for the detection of folic acid protein (FAP) using graphene-based SPR chips. The exceptional properties of CVD graphene were exploited to construct a highly sensitive and selective SPR chip for folate biomarker sensing in serum. The specific recognition of FAP is based on the interaction between folic acid receptors integrated through pi-stacking on the graphene coated SPR chip and the FAP analyte in serum. A simple post-adsorption of human serum:bovine serum albumin (HS:BSA) mixtures onto the folic acid modified sensor resulted in a highly anti-fouling interface, while keeping the sensing capabilities for folate biomarkers. This sensor allowed femtomolar (fM) detection of FAP, a detection limit well adapted and promising for quantitative clinical analysis. PMID- 26852831 TI - Recent advances in graphene-based nanomaterials for fabricating electrochemical hydrogen peroxide sensors. AB - Due to the large specific surface area, extraordinary mechanical flexibility, chemical stability, and superior electrical and thermal conductivities, graphene (G)-based materials have recently opened up an exciting field in the science and technology of two-dimensional (2D) nanomaterials with continuously growing academic and technological impetus. In the past several years, graphene-based materials have been well designed, synthesized, and investigated for sensing applications. In this review, we discuss the synthesis and application of graphene-based 2D nanomaterials for the fabrication of hydrogen peroxide (H2O2) electrochemical sensors. In particular, graphene-based nanomaterials as immobilization matrix of heme proteins for the fabrication of enzymatic H2O2 electrochemical biosensors is first summarized. Then, the application of graphene based electrocatalysts (metal-free, noble-metals and non-noble metals) in constructing non-enzymatic H2O2 electrochemical sensors is discussed in detail. We hope that this review is helpful to push forward the advancement of this academic issue (189 references). PMID- 26852832 TI - Lipid transfer and metabolism across the endolysosomal-mitochondrial boundary. AB - Lysosomes and mitochondria occupy a central stage in the maintenance of cellular homeostasis, by playing complementary roles in nutrient sensing and energy metabolism. Specifically, these organelles function as signaling hubs that integrate environmental and endogenous stimuli with specific metabolic responses. In particular, they control various lipid biosynthetic and degradative pipelines, either directly or indirectly, by regulating major cellular metabolic pathways, and by physical and functional connections established with each other and with other organelles. Membrane contact sites allow the exchange of ions and molecules between organelles, even without membrane fusion, and are privileged routes for lipid transfer among different membrane compartments. These inter-organellar connections typically involve the endoplasmic reticulum. Direct membrane contacts have now been described also between lysosomes, autophagosomes, lipid droplets, and mitochondria. This review focuses on these recently identified membrane contact sites, and on their role in lipid biosynthesis, exchange, turnover and catabolism. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon. PMID- 26852833 TI - Diclofenac plus lidocaine gel for pain relief during intrauterine device insertion. A randomized, double-blinded, placebo-controlled study. AB - OBJECTIVE: To determine the effectiveness of diclofenac potassium combined with 2% lidocaine gel in reducing the pain of intrauterine device (IUD) insertion. STUDY DESIGN: We randomized 90 parous women requesting copper T380A IUD insertion in a 1:1 ratio to active or placebo treatment. Active treatment included administration of two 50-mg diclofenac potassium tablets 1h before IUD insertion, application of 3mL of 2% lidocaine gel on the anterior cervical lip 3min before IUD insertion and placement of a cotton swab soaked in 2% lidocaine gel in the cervical canal 3min before IUD insertion. Women in the placebo group received placebo tablets and gel. Participants assessed pain intensity using a 10-cm visual analog scale (VAS). We considered a 2-cm difference in VAS pain score between both groups during IUD insertion to be a clinically significant difference. RESULTS: Subjects receiving active treatment, as compared to placebo, experienced less pain during tenaculum placement (1.66+/-0.85 vs. 2.33+/-1.19, p=.003) and IUD insertion (3.14+/-0.92 vs. 3.94+/-1.3, p=.001). Women who delivered only by cesarean section had higher pain scores with IUD insertion compared with women with previous vaginal deliveries (4.41+/-1.24 vs. 3.29+/ 1.05, p=.001). CONCLUSION: Diclofenac potassium combined with 2% lidocaine gel slightly reduced pain scores during tenaculum application and copper IUD insertion in parous women; however, the reduction in pain scores lacked clinical significance. IMPLICATIONS: Although we found a statistically significant lowering of pain scores with pretreatment with diclofenac potassium and lidocaine gel in parous women having copper IUD placement, the reduction is not clinically relevant. These findings may be more relevant for nulliparous women who experience more pain than parous women with IUD insertion and support studies of diclofenac potassium and lidocaine gel in this population. PMID- 26852837 TI - Technology, Applications, and Process Challenges of Dual Chamber Systems. AB - Dual-chamber systems provide an option as a drug and device combination product, when home care and emergency lyophilized products are intended. Nevertheless, until today, there are only a few products on the market, due to the challenges and limitations in manufacturability, product formulation, and product stability in a dual-chamber configuration, as well as economic considerations. This review serves to describe currently available dual-chamber systems and to discuss factors to be considered for appropriate selection and establishing fill-finish processes. PMID- 26852838 TI - Epidermal Growth Factor Receptor-Specific Nanoprobe Biodistribution in Mouse Models. AB - Nanotechnology offers a targeted approach to both imaging and treatment of cancer, the leading cause of death worldwide. Previous studies have found that nanoparticles with a wide variety of coatings initiate an immune response leading to sequestration in the liver and spleen. In an effort to find a nanoparticle platform which does not elicit an immune response, we created 43 nm and 44 nm of gold and silver nanoparticles coated with biomolecules normally produced by the body, alpha-lipoic acid and the epidermal growth factor (EGF), and have used mass spectroscopy to determine their biodistribution in mouse models, 24 h after tail vein injection. Relative to controls, mouse EGF (mEGF)-coated silver and gold nanoprobes are found at background levels in all organs including the liver and spleen. The lack of sequestration of mEGF-coated nanoprobes in the liver and spleen and the corresponding uptake of control nanoprobes at elevated levels in these organs suggest that the former are not recognized by the immune system. Further studies of cytokine and interleukin levels in the blood are required to confirm avoidance of an immune response. PMID- 26852839 TI - Evaluation of Incremental Siliconization Levels on Soluble Aggregates, Submicron and Subvisible Particles in a Prefilled Syringe Product. AB - The evaluation of stability with respect to particles in prefilled syringes is complicated by the presence of silicone oil. The mobility, colloidal characteristics, and kinetic instability of silicone oil in contact with a protein formulation may be influenced in unpredictable ways by pharmaceutical variables, storage, and handling conditions. To provide insight into the impact of these variables on silicone oil originating specifically from the siliconized prefillable syringe (PFS), a series of studies were conducted at incremental syringe barrel siliconization levels. Size-exclusion chromatography and particle counting methods were used to quantitate soluble aggregates and submicron and subvisible particles in peginterferon beta-1a in a PFS siliconized with a fixed nozzle spray-on siliconization process. The effect of silicone oil on the peginterferon beta-1a molecule was examined under pharmaceutically relevant conditions, accelerated degradation, and under denaturing conditions. Resonant mass measurement was used to discriminate silicone oil from protein particles establishing that silicone oil does not mask adverse trends in non-silicone oil particles. The peginterferon beta-1a molecule was shown to be stable in the presence of silicone oil and robust with respect to the formation of soluble aggregates and submicron and subvisible particles in its PFS siliconized over the range of 0-1.2 mg silicone oil per syringe barrel. PMID- 26852840 TI - Crystal Structures and Phase Relationships of 2 Polymorphs of 1,4 Diazabicyclo[3.2.2]nonane-4-Carboxylic Acid 4-Bromophenyl Ester Fumarate, A Selective alpha-7 Nicotinic Receptor Partial Agonist. AB - Two polymorphs of the 1:1 fumarate salt of 1,4-diazabicyclo[3.2.2]nonane-4 carboxylic acid 4-bromophenyl ester, developed for the treatment of cognitive symptoms of schizophrenia and Alzheimer disease, have been characterized. The 2 crystal structures have been solved, and their phase relationships have been established. The space group of form I is P21/c with a unit-cell volume of 1811.6 (5) A(3) with Z = 4. The crystals of form I were 2-component nonmerohedral twins. The space group of form II is P21/n with a unit-cell volume of 1818.6 (3) A(3) with Z = 4. Relative stabilities have been inferred from experimental and topological P-T diagrams exhibiting an overall enantiotropic relationship between forms I and II although the solid-solid transition has never been observed. The slope of the I-II equilibrium in the P-T diagram is negative, form II is the stable phase below the solid-solid transition temperature of 371 K, and form I exhibits a stable melting equilibrium. The I-II transition temperature has been obtained from the intersection of the sublimation curves of the 2 solid forms. PMID- 26852841 TI - Exploring the Phase Behavior of Monoolein/Oleic Acid/Water Systems for Enhanced Donezepil Administration for Alzheimer Disease Treatment. AB - Donepezil is a drug usually administered by oral route for Alzheimer disease treatment, but several gastric side effects have been reported as diarrhea, nausea, and anorexia. We explored the phase behavior of lyotropic liquid crystalline (LLC) mesophases composed by monoolein/oleic acid/water for enhanced administration of donepezil. Polarized light microscopy suggested that these systems ranged from isotropic inverse micellar solutions (L2) to viscous and birefringent reverse hexagonal (HII) mesophases according to the amount of water in the ternary systems. Phase transition was observed from a L2 phase to HII mesophase after swelling studies, an interesting property to be explored as a precursor of LLC mesophases for mucosal administration that increases its viscosity in situ. Mucoadhesive properties of LLC mesophases were characterized using a texture analyzer indicating that these systems can have an increased residence time in the site of absorption. Donepezil-free base was incorporated in the evaluated formulations, and their in vitro release was controlled up to 24 h. The phase behavior of the systems demonstrated a great potential for enhanced donepezil administration once these mucoadhesive-controlled release formulations can incorporate the drug and prolong its release, possibly reducing its side effects. PMID- 26852842 TI - Preparation, Characterization, and Antitumor Activities of Miriplatin-Loaded Liposomes. AB - Because of the insolubility of miriplatin in water, miriplatin and lipiodol suspension is the sole formulation of miriplatin approved in Japan to treat hepatocellular carcinoma by transcatheter arterial chemoembolization. Until now, there have been no reports of other pharmaceutical formulations of miriplatin except miriplatin/lipiodol suspension. In this study, we aimed not only to develop miriplatin-loaded liposomes (lipomiriplatins) which could be administrated systematically for tumors besides hepatocellular carcinoma but also to ascertain whether miriplatin, like its analog of NDDP, was a liposome dependent antitumor agent. We found that miriplatin could be successfully incorporated into liposomes, and both the stability and antitumor activity of lipomiriplatins were independent of the liposomal compositions. Especially, HPLC was successfully established as the quantitative method for lipomiriplatins, which completely eliminated the interference of cholesterol. Lipomiriplatins possessed favorable colloidal properties (99.71 +/- 0.56 nm, -50 mV), high drug loading capacity (about 2.2 mg/mL), excellent entrapment efficiency (>95%), and robust stability. The remarkable antitumor activities of lipomiriplatin were proved to be mediated by inducing cell apoptosis and were comparable to that of the commercial cisplatin and oxaliplatin injections, indicating that lipomiriplatins showed great promise for future potential clinical application via systematic administration. PMID- 26852843 TI - Preparation of Concentrated Chitosan/DNA Nanoparticle Formulations by Lyophilization for Gene Delivery at Clinically Relevant Dosages. AB - Chitosan/DNA polyplexes have been optimized for efficient and safe in vitro and in vivo gene delivery. Clinical application of this technology requires the development of formulations with higher concentrations to reach therapeutic dosages. Polyplexes were prepared using chitosan and EGFPLuc plasmids. Freeze thawing and freeze-drying studies were performed to identify and optimize lyoprotectant and buffer contents in formulations. Freeze-dried samples were rehydrated in reduced volumes to increase their final DNA dose. Nanoparticle physicochemical properties were analyzed, and their transfection efficiency and cytotoxicity were measured in human embryonic kidney 293 cells. Data showed that 3.5 mM histidine buffer (pH 6.5) combined with one of 0.5% wt/vol sucrose, dextran 5 kDa, or trehalose was required to prevent polyplex aggregation during freeze-drying. Optimal formulations could be concentrated 20-fold, to a clinically desired ~1 mg of DNA/mL, while maintaining near physiological pH and tonicity. Polyplexes were predominantly spherical, with diameters below 200 nm, polydispersity indexes below 0.32, and zeta potentials above +19 mV. Rehydrated formulations had transfection efficiencies no less than 65% of fresh polyplexes without excipients and had no effect on viability and metabolic activity of human embryonic kidney 293 cells. These concentrated formulations represent an important step toward clinical use of chitosan-based gene delivery systems. PMID- 26852844 TI - Spectroscopic-Based Chemometric Models for Quantifying Low Levels of Solid-State Transitions in Extended Release Theophylline Formulations. AB - Variations in the solid state form of a pharmaceutical solid have profound impact on the product quality and clinical performance. Quantitative models that allow rapid and accurate determination of polymorphic changes in pharmaceutical products are essential in ensuring product quality throughout its lifecycle. This study reports the development and validation of chemometric models of Raman and near infrared spectroscopy (NIR) for quantifying the extent of pseudopolymorphic transitions of theophylline in extended release formulations. The chemometric models were developed using sample matrices consisting of the commonly used excipients and at the ratios in commercially available products. A combination of scatter removal (multiplicative signal correction and standard normal variate) and derivatization (Savitzky-Golay second derivative) algorithm were used for data pretreatment. Partial least squares and principal component regression models were developed and their performance assessed. Diagnostic statistics such as the root mean square error, correlation coefficient, bias and Q(2) were used as parameters to test the model fit and performance. The models developed had a good fit and performance as shown by the values of the diagnostic statistics. The model diagnostic statistics were similar for MSC-SG and SNV-SG treated spectra. Similarly, PLSR and PCR models had comparable performance. Raman chemometric models were slightly better than their corresponding NIR model. The Raman and NIR chemometric models developed had good accuracy and precision as demonstrated by closeness of the predicted values for the independent observations to the actual TMO content hence the developed models can serve as useful tools in quantifying and controlling solid state transitions in extended release theophylline products. PMID- 26852845 TI - Influence of 24-Nor-Ursodeoxycholic Acid on Hepatic Disposition of [(18)F]Ciprofloxacin, a Positron Emission Tomography Study in Mice. AB - 24-nor-ursodeoxycholic acid (norUDCA) is a novel therapeutic approach to cholestatic liver diseases. In mouse models of cholestasis, norUDCA induces basolateral multidrug resistance-associated proteins 4 (Mrp4) and 3 in hepatocytes, which provide alternative escape routes for bile acids accumulating during cholestasis but could also result in altered hepatic disposition of concomitantly administered substrate drugs. We used positron emission tomography imaging to study the influence of norUDCA on hepatic disposition of the model Mrp4 substrate [(18)F]ciprofloxacin in wild-type and Mdr2((-/-)) mice, a model of cholestasis. Animals underwent [(18)F]ciprofloxacin positron emission tomography at baseline and after norUDCA treatment. After norUDCA treatment, liver-to-blood area under the curve ratio of [(18)F]ciprofloxacin was significantly decreased compared to baseline, both in wild-type (-34.0 +/- 2.1%) and Mdr2((-/-)) mice ( 20.5 +/- 6.0%). [(18)F]Ciprofloxacin uptake clearance from blood into liver was reduced by -17.1 +/- 9.0% in wild-type and by -20.1 +/- 7.3% in Mdr2((-/-)) mice. Real-time PCR analysis showed significant increases in hepatic Mrp4 and multidrug resistance-associated protein 3 mRNA after norUDCA. Transport experiments in organic anion transporting polypeptide (OATP)1B1-, OATP1B3-, and OATP2B1 transfected cells revealed weak transport of [(14)C]ciprofloxacin by OATP1B3 and OATP2B1 and no inhibition by norUDCA. In conclusion, our data suggest that changes in hepatic [(18)F]ciprofloxacin disposition in mice after norUDCA treatment were caused by induction of basolateral Mrp4 in hepatocytes. PMID- 26852846 TI - Formulation and Evaluation of a Mucoadhesive Thermoresponsive System Containing Brazilian Green Propolis for the Treatment of Lesions Caused by Herpes Simplex Type I. AB - The aim of the present work was to develop a topical delivery system that contains Brazilian green propolis extract (PE-8) to increase efficiency and convenience when applied to herpetic lesions. The cytotoxicity and antiherpetic activity was determined in vitro and in vivo. The PE-8 was added to a system that contained poloxamer 407 and carbopol 934P. The in vitro characterization of the system included rheological studies, texture profile analysis, and mucoadhesion analysis. The PE-8 inhibited the virus during the phase of viral infection, induced virion damage, and exhibited an ability to protect cells from viral infection. The system had advantageous mucoadhesive properties, including a suitable gelation temperature of approximately 25 degrees C for topical delivery, a desirable textural profile, and pseudoplastic behavior. The in vitro release study showed a rapid initial release of the PE-8 in the first 3 h, and the rate of drug release remained constant for up to 24 h. The system appeared to be macroscopically and microscopically innocuous to skin tissue. Therefore, the mucoadhesive thermoresponsive system that contained the PE-8 appears to be promising for increasing bioavailability and achieving prolonged release of the PE-8 when applied to skin lesions caused by herpes simplex virus type 1. PMID- 26852847 TI - Intra-articular Administration of Chitosan Thermosensitive In Situ Hydrogels Combined With Diclofenac Sodium-Loaded Alginate Microspheres. AB - The aims of this study were to prepare fine intra-articular-administrated chitosan thermosensitive hydrogels combined with alginate microspheres and to investigate the possibility of those hydrogels as a drug delivery system for promoting the anti-inflammation effect. Diclofenac sodium containing alginate microspheres was prepared by a modified emulsification and/or gelation method and then dispersed into injectable thermosensitive hydrogels, consisting of chitosan and beta-glycerophosphate. The final combined hydrogels were evaluated in terms of their morphology properties, rheological properties, in vitro drug release, and in vivo biocompatibility and pharmacodynamics behaviors. The optimized formulation exhibited sol-gel transition at 31.72 +/- 0.42 degrees C and quickly turned into gel within 5 min, with sustained drug release characteristics followed Ritger-Peppas equation, which could prolong the in vitro drug release to 5 days. In addition, the anti-inflammation efficacy of the combined hydrogels in rabbits with experimental rheumatoid arthritis was higher than that of drug solution and pure chitosan hydrogels. Those results demonstrated that these combined hydrogels could become a potential drug delivery system for improving the therapeutic effect of diclofenac sodium and suggested an important technology platform for intra-articular administration. PMID- 26852848 TI - Simultaneous Rapid Determination of the Solubility and Diffusion Coefficients of a Poorly Water-Soluble Drug Based on a Novel UV Imaging System. AB - The solubility and diffusion coefficient are two of the most important physicochemical properties of a drug compound. In practice, both have been measured separately, which is time consuming. This work utilizes a novel technique of UV imaging to determine the solubility and diffusion coefficients of poorly water-soluble drugs simultaneously. A 2-step optimal method is proposed to determine the solubility and diffusion coefficients of a poorly water-soluble pharmaceutical substance based on the Fick's second law of diffusion and UV imaging measurements. Experimental results demonstrate that the proposed method can be used to determine the solubility and diffusion coefficients of a drug with reasonable accuracy, indicating that UV imaging may provide a new opportunity to accurately measure the solubility and diffusion coefficients of a poorly water soluble drug simultaneously and rapidly. PMID- 26852849 TI - Degradation Kinetics and Mechanism of a beta-Lactam Antibiotic Intermediate, 6 Aminopenicillanic Acid, in a New Integrated Production Process. AB - In an effort to promote sustainability and to reduce manufacturing costs, the traditional production process for 6-aminopenicillanic acid (6-APA) has been modified to include less processing units. The objectives of this study are to investigate the degradation kinetics of 6-APA, to propose a reasonable degradation mechanism, and to optimize the manufacturing conditions within this new process. A series of degradation kinetic studies were conducted in the presence of impurities, as well as at various chemical and physical conditions. The concentrations of 6-APA were determined by high-performance liquid chromatography. An Arrhenius-type kinetic model was established to give a more accurate prediction on the degradation rates of 6-APA. A hydrolysis degradation mechanism is shown to be the major pathway for 6-APA. The degradation mechanisms and the kinetic models for 6-APA in the new system enable the design of a good manufacturing process with optimized parameters. PMID- 26852851 TI - Oscillatory Shear Rheology in Examining the Drug-Polymer Interactions Relevant in Hot Melt Extrusion. AB - The flow properties of drug-polymer mixtures have a significant influence on their processability when using techniques such as hot melt extrusion (HME). Suitable extrusion temperature and screw speed to be used in laboratory scale HME were evaluated for mixtures containing 30% of paracetamol (PRC), ibuprofen (IBU), or indomethacin (IND), and 70% of polyethylene oxide, by using small amplitude oscillatory shear rheology. The initial evaluation of the drug:polyethylene oxide solubility was estimated by differential scanning calorimetry of the physical mixtures containing a wide range of weight fractions of the drug substances. Consecutively, the mixtures were extruded, and the maximum plasticizing weight fraction of each drug was determined by means of rheological measurements. IBU was found to have an efficient plasticizing functionality, decreasing the viscosity of the mixtures even above its apparent saturation solubility, whereas IND and PRC initially lowered the viscosity of the mixture slightly but increased it significantly with increasing drug load. The main reason for the enhanced plasticization effect seems to be the lower melting temperature of IBU, which is closer to the used HME temperature, compared to PRC and IND. This study highlights the importance of rheological investigation in understanding the drug polymer interactions in melt processing. PMID- 26852850 TI - Current Inhalers Deliver Very Small Doses to the Lower Tracheobronchial Airways: Assessment of Healthy and Constricted Lungs. AB - To evaluate the regional delivery of conventional aerosol medications, a new whole-lung computational fluid dynamics modeling approach was applied for metered dose inhaler (MDI) and dry powder inhaler (DPI) aerosols delivered to healthy and constricted airways. The computational fluid dynamics approach included complete airways through the third respiratory bifurcation (B3) and applied the new stochastic individual pathway modeling technique beyond B3 through the remainder of the conducting airways together with a new model of deposition in the alveolar region. Bronchiolar (B8-B15) deposition fraction values were low (~1%) for both MDI and DPI aerosols with the healthy geometry, whereas delivery to the constricted model was even lower, with deposition fraction values of 0.89% and 0.81% for the MDI and DPI, respectively. Calculating dose per unit surface area for the commercial MDI and DPI products resulted in approximately 10(-3) MUg/cm(2) in the lower tracheobronchial region of B8-B15 and 10(-4) MUg/cm(2) in the alveolar region. Across the lung, dose per unit surface area varied by 2 orders of magnitude, which increased to 4 orders of magnitude when the mouth throat region was included. The MDI and DPI both provided very low drug dose per unit surface area to the small tracheobronchial and alveolar airways. PMID- 26852852 TI - Integrated Application of Quality-by-Design Principles to Drug Product Development: A Case Study of Brivanib Alaninate Film-Coated Tablets. AB - Modern drug product development is expected to follow quality-by-design (QbD) paradigm. At the same time, although there are several issue-specific examples in the literature that demonstrate the application of QbD principles, a holistic demonstration of the application of QbD principles to drug product development and control strategy, is lacking. This article provides an integrated case study on the systematic application of QbD to product development and demonstrates the implementation of QbD concepts in the different aspects of product and process design for brivanib alaninate film-coated tablets. Using a risk-based approach, the strategy for development entailed identification of product critical quality attributes (CQAs), assessment of risks to the CQAs, and performing experiments to understand and mitigate identified risks. Quality risk assessments and design of experiments were performed to understand the quality of the input raw materials required for a robust formulation and the impact of manufacturing process parameters on CQAs. In addition to the material property and process parameter controls, the proposed control strategy includes use of process analytical technology and conventional analytical tests to control in-process material attributes and ensure quality of the final product. PMID- 26852853 TI - Process Analytical Technology for High Shear Wet Granulation: Wet Mass Consistency Reported by In-Line Drag Flow Force Sensor Is Consistent With Powder Rheology Measured by At-Line FT4 Powder Rheometer. AB - Drag flow force (DFF) sensor that measures the force exerted by wet mass in a granulator on a thin cylindrical probe was shown as a promising process analytical technology for real-time in-line high-resolution monitoring of wet mass consistency during high shear wet granulation. Our previous studies indicated that this process analytical technology tool could be correlated to granulation end point established independently through drug product critical quality attributes. In this study, the measurements of flow force by a DFF sensor, taken during wet granulation of 3 placebo formulations with different binder content, are compared with concurrent at line FT4 Powder Rheometer characterization of wet granules collected at different time points of the processing. The wet mass consistency measured by the DFF sensor correlated well with the granulation's resistance to flow and interparticulate interactions as measured by FT4 Powder Rheometer. This indicated that the force pulse magnitude measured by the DFF sensor was indicative of fundamental material properties (e.g., shear viscosity and granule size/density), as they were changing during the granulation process. These studies indicate that DFF sensor can be a valuable tool for wet granulation formulation and process development and scale up, as well as for routine monitoring and control during manufacturing. PMID- 26852854 TI - Essential Fatty Acids as Transdermal Penetration Enhancers. AB - The aim of this study was to investigate the effect of different penetration enhancers, containing essential fatty acids (EFAs), on the transdermal delivery of flurbiprofen. Evening primrose oil (EPO), vitamin F, and Pheroid technology all contain fatty acids and were compared using a cream-based formulation. This selection was to ascertain whether EFAs solely, or EFAs in a Pheroid delivery system, would have a significant increase in the transdermal delivery of a compound. Membrane release studies were performed, and the results indicated the following rank order for flurbiprofen release from the different formulations: vitamin F >> control > EPO >> Pheroid. Topical skin delivery results indicated that flurbiprofen was present in the stratum corneum-epidermis and the epidermis dermis. The average percentage flurbiprofen diffused to the receptor phase (representing human blood) indicated that the EPO formulation showed the highest average percentage diffused. The Pheroid formulation delivered the lowest concentration with a statistical significant difference (p < 0.05) compared with the control formulation (containing 1% flurbiprofen and no penetration enhancers). The control formulation presented the highest average flux, with the EPO formulation following the closest. It could, thus, be concluded that EPO is the most favorable chemical penetration enhancer when used in this formulation. PMID- 26852856 TI - In Vivo Inverse Correlation in the Activation of Natural Killer T Cells Through Dual-Signal Stimulation via a Combination of alpha-Galactosylceramide-Loaded Liposomes and Interleukin-12. AB - Alpha-galactosylceramide (GC) represents a potentially new class of adjuvant because GC strongly induces interferon (IFN) gamma production from natural killer T (NKT) cells, leading to the induction of strong antitumor immunity. Interleukin (IL)-12 is another stimulating signal that induces IFN-gamma production by NKT cells. We report herein on an investigation of the effect of recombinant IL-12 on NKT cell activation, when used in combination with GC-loaded octaarginine modified liposomes (GC-Lip). IFN-gamma production from splenocytes simulated with GC-Lip was dose dependently enhanced in the presence of IL-12 in vitro. In contrast, IFN-gamma production in vivo was enhanced at a low dose of IL-12. Enhanced IFN-gamma production was observed in the case of low doses (0.5 MUg and 2.5 MUg) of GC-Lip but not a high dose (5 MUg), that is, the IL-12 combination enhanced NKT cell activation at a 10-fold lower GC dose. The use of the above combination also enhanced the expansion of the NKT cell population. These findings indicate that in vivo IFN-gamma production is inversely correlated with the dose of IL-12 during dual signal stimulation of NKT cells via both GC-Lip and IL-12, indicating that the dose of GC-Lip can be reduced without weakening NKT cell activation. PMID- 26852855 TI - Preparation and Physicochemical and Pharmacokinetic Characterization of Ginkgo Lactone Nanosuspensions for Antiplatelet Aggregation. AB - The aim of this study was to investigate the potential of nanosuspensions (NSs) in improving the dissolution and absorption of poorly water-soluble ginkgo lactones (GLs), including ginkgolide A, ginkgolide B, and ginkgolide C. Liquid GL NSs were prepared by a combined bottom-up and top-down approach with response surface methodology design, followed by freeze-drying solidification. Physicochemical characterization of the prepared freeze-dried GL-NSs was performed by photon correlation spectroscopy, scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. In vitro dissolution and in vivo bioavailability of ginkgolide A, ginkgolide B, and ginkgolide C in freeze-dried GL-NSs were evaluated with GLs coarse powder as control. Their inhibitory effects on platelet aggregation were also comparatively analyzed. GLs existed in an amorphous state in the prepared freeze-dried GL-NSs. The particle size, polydispersity index, zeta potential, and redispersibility index of freeze-dried GL-NSs were around 286 nm, 0.26, -25.19 mV, and 112%, respectively. The particle size reduction resulted in much more rapid and complete dissolution of ginkgolides from GL-NSs than coarse powder. Comparison with GLs coarse powder, freeze-dried GL-NSs showed a significant decreased Tmax, 2-fold higher peak concentration, and 2-fold higher area under plasma concentrations curve for 3 ginkgolides and exhibited significantly higher antiplatelet aggregation effect. PMID- 26852857 TI - Rational Design and Characterization of a Nanosuspension for Intraoral Administration Considering Physiological Conditions. AB - The oral cavity displays an attractive route in drug administration that is not associated with gastric transit and hepatic first-pass metabolism. However, limiting factors for an efficient transit of drugs through the oral mucosa are poor water solubility and permeability. Hence, various strategies exist to enhance solubility. Specifically, nanotechnology has attracted much research interest in the past decade. This study aimed at developing a stable nanosuspension of the model compound phenytoin via wet media milling. The nanosuspensions were carefully characterized regarding hydrodynamic particle sizes, crystallinity, and dissolution characteristics under nonphysiological or physiological (salivary) conditions. The permeability of bulk phenytoin and nanophenytoin through a buccal in vitro and ex vivo model was investigated, and the apparent permeability coefficients were determined. Moreover, cytotoxicity studies were conducted. The addition of Tween 80 as stabilizer resulted in a stable crystalline nanosuspension (330 nm). The solubility characteristics significantly increased under salivary conditions, which further impacted the permeability, as the steady state appearance rate of nanosized phenytoin was 1.4 fold higher. Cytotoxicity studies demonstrated that bulk-/nano-phenytoin exhibited no harmful effects. It can be concluded that the salivary environment (i.e., ionic strength, pH) strongly impacts the solubility and consequently the permeability of crystalline nanosuspensions across the buccal mucosa. PMID- 26852858 TI - Sialoganglioside Micelles for Enhanced Paclitaxel Solubility: In Vitro Characterization. AB - Efficiency of mono-sialogangliosides to load Paclitaxel (Ptx) has recently been found to depend on the structure of the polysaccharide chain. In this study, we demonstrated that incorporation of only one more sialic acid into the ganglioside molecule, independently of its position, causes a 4-fold increase in Ptx-loading capacity, the maximum being at a 5:1 molar ratio (di-sialoganglioside/Paclitaxel, GD/Ptx). These complexes are stable in solution for at least 3 months, and over 90% of Ptx remains loaded in the micelles after extreme stress conditions such as high-speed centrifugation, lyophilization, or freeze-thaw cycles. Ganglioside micelles protect 50% of the initially loaded Ptx from alkaline hydrolysis after 24 h at pH 10. Dynamic light scattering studies revealed that GD micelles increase their size from 9 to 12 nm when loaded with Ptx. Transmission electron microscopy shows a homogeneous population of spherical micelles either with or without Ptx. In vitro biological activity was similar to that of the free drug. These results provide further options of self-assembled nanostructures of di- and tri-sialogangliosides with a higher loading capacity. PMID- 26852859 TI - Novel Antitransferrin Receptor Antibodies Improve the Blood-Brain Barrier Crossing Efficacy of Immunoliposomes. AB - Surface functionalization with antitransferrin receptor (TfR) mAbs has been suggested as the strategy to enhance the transfer of nanoparticles (NPs) across the blood-brain barrier (BBB) and to carry nonpermeant drugs from the blood into the brain. However, the efficiency of BBB crossing is currently too poor to be used in vivo. In the present investigation, we compared 6 different murine mAbs specific for different epitopes of the human TfR to identify the best performing one for the functionalization of NPs. For this purpose, we compared the ability of mAbs to cross an in vitro BBB model made of human brain capillary endothelial cells (hCMEC/D3). Liposomes functionalized with the best performing mAb (MYBE/4C1) were uptaken, crossed the BBB in vitro, and facilitated the BBB in vitro passage of doxorubicin, an anticancer drug, 3.9 folds more than liposomes functionalized with a nonspecific IgG, as assessed by confocal microscopy, radiochemical techniques, and fluorescence, and did not modify the cell monolayer structural or functional properties. These results show that MYBE/4C1 antihuman TfR mAb is a powerful resource for the enhancement of BBB crossing of NPs and is therefore potentially useful in the treatment of neurologic diseases and disorders including brain carcinomas. PMID- 26852860 TI - Combined Treatment of Tyrosine Kinase Inhibitor-Labeled Gold Nanorod Encapsulated Albumin With Laser Thermal Ablation in a Renal Cell Carcinoma Model. AB - To characterize and evaluate human serum albumin-encapsulated nanoparticles for drug delivery of a tyrosine kinase inhibitor combined with induction of photothermal ablation combination therapy of renal cell carcinoma (RCC), nanoparticles of varying preparations and concentrations were characterized via zeta potential, drug loading, and release profile. Cytotoxicity and uptake trials were also studied using clear cell RCC cell line RCC 786-0, a human metastatic carcinoma. Target temperatures of >50 degrees C were consistently attained by 0.1 and 0.05 MUM concentrations of irradiated human serum albumin nanoparticle-gold nanorods (HSAP-AuNRs). Irradiated trials of HSAP-AuNRs demonstrated significantly decreased cell viabilities compared with nonirradiated "dark" controls (p < 0.01). Increasing loaded masses of sorafenib (SRF) also significantly decreased relative cell viability of RCC (p < 0.05). Photothermal ablation using HSAP-AuNRs is capable of inducing significant hyperthermia while the loading of SRF further enhances cytotoxicity relative to treatment with HSAP-AuNRs alone. HSAP-AuNR-SRFs have the potential to be an effective, novel combination treatment for advanced RCC. PMID- 26852861 TI - The Pharmacokinetics and Biodistribution of a 64 kDa PolyPEG Star Polymer After Subcutaneous and Pulmonary Administration to Rats. AB - PolyPEG star polymers have potential utility as cost-effective polymeric drug delivery vehicles, and as such, it is important to develop an understanding of their biopharmaceutical behavior. Moreover, although a number of studies have evaluated the utility of PolyPEG stars in vitro, investigation of these novel materials in vivo has been limited. Herein, we evaluated the pharmacokinetics of a 64 kDa tritiated PEG-based star polymer after subcutaneous and pulmonary administration in rats. After subcutaneous administration, the star polymer showed near complete bioavailability (~80%) and a similar organ biodistribution profile to the polymer after intravenous administration. After intratracheal instillation to the lungs, the star polymer showed limited bioavailability (~3%), and most of the administered radiolabel was recovered in lung tissue and feces after 6 d. The data reported here suggest that star polymers display similar pharmaceutical behavior to PEGylated dendrimers after subcutaneous and inhaled delivery and may therefore be used as similar, but more cost-effective drug delivery vehicles. PMID- 26852862 TI - Population Pharmacokinetic-Toxicodynamic Modeling and Simulation of Cisplatin Induced Acute Renal Injury in Rats: Effect of Dosing Rate on Nephrotoxicity. AB - Nephrotoxicity is the major dose-limiting toxicity of cisplatin (CDDP). The aim of this study was to develop a pharmacokinetic (PK)/toxicodynamic (TD) model of CDDP-induced acute renal injury in rats and to simulate nephrotoxicity at various dosing rates. CDDP was administered to rats by a 30-s bolus or a 2-h infusion (1.0, 2.5, 5.0, and 7.5 mg/kg). Unbound CDDP concentrations in plasma and urine were determined up to 2 h after administration in the PK study, and plasma creatinine (Cr) levels were monitored for up to 7 days as an index of nephrotoxicity in the TD study. The PK was linear and was fitted with a traditional 2-compartment model. The TD was nonlinear and differed between dosing rates. The creatinine concentration profiles were fitted with a signal transduction-indirect response model. Population analysis using a nonlinear mixed effect model was adapted to the developed PK/TD model and was well-validated. Dosing simulations from the developed population PK/TD model indicated that CDDP induced nephrotoxicity was due to not only Cmax but also the time above the toxic concentration of CDDP. Prolongation of infusion time will not necessarily attenuate acute nephrotoxicity. This study demonstrated the potential utility of PK/TD modeling for preventing nephrotoxicity. PMID- 26852863 TI - 1,25-Dihydroxyvitamin D Enhances Alveolar Fluid Clearance by Upregulating the Expression of Epithelial Sodium Channels. AB - Vitamin D is implicated in the pathogenesis of asthma, acute lung injury, and other respiratory diseases. 1,25-Dihydroxyvitamin D (1,25(OH)2D3), the hormonal form of vitamin D, has been shown to reduce vascular permeability and ameliorate lung edema. Therefore, we speculate that 1,25(OH)2D3 may regulate alveolar Na(+) transport via targeting epithelial Na(+) channels (ENaC), a crucial pathway for alveolar fluid clearance. In vivo total alveolar fluid clearance was 39.4 +/- 3.8% in 1,25(OH)2D3-treated mice, significantly greater than vehicle-treated controls (24.7 +/- 1.9 %, n = 10, p < 0.05). 1,25(OH)2D3 increased amiloride sensitive short-circuit currents in H441 monolayers, and whole-cell patch-clamp data confirmed that ENaC currents in single H441 cell were enhanced in 1,25(OH)2D3-treated cells. Western blot showed that the expression of alpha-ENaC was significantly elevated in 1,25(OH)2D3-treated mouse lungs and 1,25(OH)2D3 treated H441 cells. These observations suggest that vitamin D augments transalveolar fluid clearance, and vitamin D therapy may potentially be used to ameliorate pulmonary edema. PMID- 26852864 TI - Interaction of Peptide Transporter 1 With D-Glucose and L-Glutamic Acid; Possible Involvement of Taste Receptors. AB - We investigated the influence of sweet and umami (savory) tastants on the intestinal absorption of cephalexin (CEX), a substrate of peptide transporter 1 (PEPT1, SLC15A1) in rats. After oral administration of glucose or mannitol to rats, CEX was administered together with a second dose of glucose or mannitol. Western blot analysis indicated that expression of PEPT1 in rat jejunum membrane was decreased by glucose, compared to mannitol. Furthermore, the maximum plasma concentration (Cmax) of orally administered CEX was reduced by glucose compared to mannitol. The effect of glucose was diminished by nifedipine, a L-type Ca(2+) channel blocker. We also found that Cmax of orally administered CEX was reduced by treatment with L-glutamic acid, compared to D-glutamic acid. Thus, excessive intake of glucose and L-glutamic acid may impair oral absorption of PEPT1 substrates. PMID- 26852865 TI - Increased Systemic Exposure of Methotrexate by a Polyphenol-Rich Herb via Modulation on Efflux Transporters Multidrug Resistance-Associated Protein 2 and Breast Cancer Resistance Protein. AB - Scutellariae radix (SR, roots of Scutellaria baicalensis Georgi), a popular Chinese medicine, contains plenty of flavonoids such as baicalin, wogonoside, baicalein, and wogonin. Methotrexate (MTX), an important immunosuppressant with a narrow therapeutic index, is a substrate of multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). This study investigated the effect of SR on MTX pharmacokinetics and the underlying mechanisms. Rats were orally administered MTX alone and with 1.0 or 2.0 g/kg of SR. The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. Cell models were used to explore the involvement of MRP2 and BCRP in the interaction. The results showed that 1.0 g/kg of SR significantly increased Cmax, AUC(0-30), AUC(0-2880), and mean residence time (MRT) of MTX by 50%, 45%, 501%, and 347%, respectively, and 2.0 g/kg of SR significantly enhanced the AUC(0-2880) and MRT by 242% and 293%, respectively, but decreased AUC(0-30) by 41%. Cell line studies indicated that SR activated the BCRP-mediated efflux transport, whereas the serum metabolites of SR inhibited both the BCRP- and MRP2-mediated efflux transports. In conclusion, SR ingestion increased the systemic exposure and MRT of MTX via modulation on MRP2 and BCRP. PMID- 26852866 TI - Intratablet S-nitrosation: A New Approach for the Oral Administration of S nitrosothiols as Nitric Oxide Donors. AB - The primary S-nitrosothiol, S-nitroso-N-acetylcysteine (SNAC) is a nitric oxide donor with potential pharmaceutical applications for the oral treatment of hepatic steatosis and cirrhosis and for protection against gastric acid-peptic disorders. However, its low thermal stability precludes the preparation of stable dosage forms based on presynthesized SNAC. In this study, we describe an innovative strategy for the oral administration of SNAC based on its intratablet formation via the S-nitrosation reaction of its parent stable thiol, N-acetyl-L cysteine by nitrous acid during the absorption of water by the tablet. The proposed strategy allows for the manufacturing of thermally stable oral dosage forms for the controlled release of SNAC in the enteric medium. PMID- 26852867 TI - Assessing the Environment for Support of Youth Physical Activity in Rural Communities. AB - OBJECTIVE: Assess environmental support of physical activity (PA) in rural areas and determine whether there is a correlation between the measured environment for PA and participant perceptions of the environment for PA. DESIGN: The PA environment was assessed using the Active Neighborhood Checklist (ANC) and the Physical Activity Resource Assessment (PARA). Youth behavior and perceptions related to PA and the local environment were assessed using 5 questions from previously validated tools. SETTING: Four rural low-income communities in South Dakota and Kansas. PARTICIPANTS: Sixth- through eighth-grade youth. VARIABLES MEASURED: Physical Activity Resource Assessment, ANC, behavior, and perception. ANALYSIS: The authors used ANOVA to determine whether there were differences in ANC, PARA, and Perception of the Environment scores among communities. Pearson correlations were used to assess associations between ANC and student perception of the environment and PARA and student perception of the environment. RESULTS: There were no differences in total ANC or total PARA among communities. Perception was weakly correlated with total ANC (multivariate coefficient, 0.016; P = .026; n = 308) but not total PARA. CONCLUSIONS AND IMPLICATIONS: Perception of PA in rural communities may not match objective measures. Future research should work toward refining and improving existing environmental audit tools and developing new, comprehensive, location-specific tools. PMID- 26852868 TI - Would German physicians opt for pay-for-performance programs? A willingness-to accept experiment in a large general practitioners' sample. AB - BACKGROUND: Implementing pay-for-performance (P4P) programs is a non-trivial task. As evaluation studies showed, P4P programs often failed to improve performance quality. A crucial element for the successful implementation of P4P is to gain acceptance with health care providers. OBJECTIVES: The aim of our study was to determine, if (and at what bonus rate) German general practitioners (GPs) would participate in a P4P program. We further examined differences between respondents who would participate in a P4P program (participants) versus respondents who would not participate (non-participants). METHODS: A mail survey was conducted among 2493 general practitioners (GPs) in Lower Saxony (with a response rate of 36.2%). The questionnaire addressed attitudes toward P4P and included a willingness to accept experiment concerning P4P implementation. RESULTS: The participation rate increased from 28% (at a bonus of 2.5%) to 50% (at a bonus of 20%). Participants showed better performance in target achievement and expected higher gains from P4P than non-participants. Major attitude differences were found in assessing feasibility of P4P, incentivizing performance and unintended consequences. The crucial factor for (not) accepting P4P might be the sense of (un)fairness of P4P. CONCLUSION: To convince GPs to participate in P4P, better evidence for the effectiveness of P4P is required. To address the concerns of GPs, future endeavors should be directed to tailoring P4P programs. Finally, program implementation must be well communicated and thoroughly discussed with health care providers. PMID- 26852869 TI - Exploration of a novel object in late adolescence predicts novelty-seeking behavior in adulthood: Associations among behavioral responses in four novelty seeking tests. AB - The sensation/novelty seeking behavioral trait refers to the exploration/preference for a novel environment. Novelty seeking increases during late adolescence and it has been associated with several neurobehavioral disorders. In this experiment, we asked whether inbred Roman high- and low avoidance (RHA-I, RLA-I) rats (1) differ in novelty seeking in late adolescence and (2) whether late adolescent novelty seeking predicts this trait in adulthood. Thirty six male RHA-I and 36 RLA-I rats were exposed to a novel object exploration (NOE) test during late adolescence (pnd: 52-59; DEPENDENT VARIABLES: contact latency, contact time, contact frequency). Head-dipping (hole-board, HB), time and visits to a novel-arm (Y-maze), and latency-in and emergence latency (emergence test) were registered in adulthood (pnd: 83-105). The results showed strain differences in all these tests (RHA-I>RLA-I). Factor analysis (RHA-I+RLA I) revealed two clusters. The first one grouped HB and emergence test measures. The second one grouped NOE and Y-maze variables. Time exploring a novel object (NOE) was a significant predictor of novel arm time (RHA-I+RLA, RHA-I); contact latency was a significant predictor of novel arm frequency (RLA-I). Present results show consistent behavioral associations across four novelty-seeking tests and suggest that late adolescent novelty seeking predicts this genetically influenced temperamental trait in adult Roman rats. PMID- 26852870 TI - Influence of nuclear quantum effects on frozen phonon simulations of electron vortex beam HAADF-STEM images. AB - We have evaluated atomic resolution high-angle annular dark field images with ordinary beams and electron vortex beams for thin crystals of bcc iron, explicitly considering the atomic vibrations using molecular dynamics. The shape of the image representing an atomic column depends on the orbital angular momentum, sample thickness and temperature. For electron vortex beams we observe characteristic doughnut-shaped images of atomic columns. It is shown how the thermal diffuse scattering reduces the depth of their central minima, which get further smeared by finite source size effects. In addition, it is shown that in calculations of HAADF-STEM images at low temperatures one has to explicitly consider the nuclear quantum effects (zero point vibrations), otherwise the effect of atomic vibrations is strongly underestimated. PMID- 26852871 TI - Design of Nanostructured Heterogeneous Solid Ionic Coatings through a Multiscale Defect Model. AB - Understanding of the electrical conduction, that is, ionic and electronic conduction, through the solid electrolyte interphase (SEI) is critical to the design of durable lithium-ion batteries (LIBs) with high rate capability and long life. It is believed that an ideal SEI should not only be an ionic conductor, but also an electronic insulator. In this study, we present a theoretical design of an artificial SEI consisting of lithium fluoride (LiF) and lithium carbonate (Li2CO3) on a LIB anode based on a newly developed density functional theory (DFT) informed space charge model. We demonstrate that the migration of lattice Li ions from LiF phase to form Li interstitials in Li2CO3 is energetically favorable near the LiF/Li2CO3 interface. At equilibrium, this interfacial defect reaction establishes a space charge potential across the interface, which causes the accumulation of ionic carriers but the depletion of electronic carriers near the LiF/Li2CO3 interface. To utilize this space charge effect, we propose a computationally designed, nanostructured artificial SEI structure with high density of interfaces of LiF and Li2CO3 perpendicular to the electrode. On the basis of this structure, the influences of grain size and volume ratio of the two phases were studied. Our results reveal that reducing the grain size of Li2CO3 in the nanostructured composite can promote ionic carriers and increase the ionic conductivity through the composite SEI by orders of magnitude. At the same time, the electronic conductivity is reduced due to electron depletion near the LiF/Li2CO3 interface. Furthermore, an optimal volume fraction that ensures high ionic and low electronic conduction was predicted. PMID- 26852872 TI - Redesign of a spine board: Proof of concept evaluation. AB - Sacral pressure ulcers are a significant problem in individuals following spinal cord injury (SCI) and are felt to be in part due to the high interface-pressures applied to the body while lying on a standard spine board (SSB) during emergency transport. The aim of the present study was to assess the interface pressures and sensing areas between the body and the SSB and two proof of concept spine board prototypes (P-1 and P-2). Ten able-bodied individuals were assessed on each board. Interface pressures and sensing area were recorded every minute over 15 minutes. The highest pressure was generated at the sacral-iliac region. The mean of the peak pressures on the SSB, P-1, and P-2 was 288.6, 202.8, and 102.8 mmHg, respectively. The mean of the sensing areas on the SSB, P-1, and P-2 was 78.2, 98.5, and 109.4 in(2), respectively. An analysis using pairwise comparisons test showed the interface pressures were significantly reduced (p = 0.003) and the sensing area was significantly increased (p < 0.001) on P-2 in the sacral-iliac location. This study's procedures can be used when determining critical factors to guide the redesign of an SSB that reduces interface pressure and increases sensing area. PMID- 26852874 TI - Synthesis, characterization and enhanced photocatalytic CO2 reduction activity of graphene supported TiO2 nanocrystals with coexposed {001} and {101} facets. AB - It is known that the combination of TiO2 and graphene and the control of TiO2 crystal facets are both effective routes to improve the photocatalytic performance of TiO2. Here, we report the synthesis and the photocatalytic CO2 reduction performance of graphene supported TiO2 nanocrystals with coexposed {001} and {101} facets (G/TiO2-001/101). The combination of TiO2 and graphene enhanced the crystallinity of TiO2 single nanocrystals and obviously improved their dispersion on graphene. The "surface heterojunction" formed by the coexposed {001} and {101} facets can promote the spatial separation of photogenerated electrons and holes toward different facets and the supports of graphene can further enhance the separation through accelerated electron migration from TiO2 to graphene. The G/TiO2-001/101 exhibited high photocatalytic CO2-reduction activity with a maximum CO yield reaching 70.8 MUmol g(-1) h(-1). The enhanced photocatalytic activity of the composites can be attributed to their high surface area, good dispersion of TiO2 nanoparticles, and effective separation of excited charges due to the synergy of graphene supports and the co exposure of {001} and {101} facets. PMID- 26852876 TI - Modern main group chemistry. PMID- 26852875 TI - Microplastics in the Terrestrial Ecosystem: Implications for Lumbricus terrestris (Oligochaeta, Lumbricidae). AB - Plastic debris is widespread in the environment, but information on the effects of microplastics on terrestrial fauna is completely lacking. Here, we studied the survival and fitness of the earthworm Lumbricus terrestris (Oligochaeta, Lumbricidae) exposed to microplastics (Polyethylene, <150 MUm) in litter at concentrations of 7, 28, 45, and 60% dry weight, percentages that, after bioturbation, translate to 0.2 to 1.2% in bulk soil. Mortality after 60 days was higher at 28, 45, and 60% of microplastics in the litter than at 7% w/w and in the control (0%). Growth rate was significantly reduced at 28, 45, and 60% w/w microplastics, compared to the 7% and control treatments. Due to the digestion of ingested organic matter, microplastic was concentrated in cast, especially at the lowest dose (i.e., 7% in litter) because that dose had the highest proportion of digestible organic matter. Whereas 50 percent of the microplastics had a size of <50 MUm in the original litter, 90 percent of the microplastics in the casts was <50 MUm in all treatments, which suggests size-selective egestion by the earthworms. These concentration-transport and size-selection mechanisms may have important implications for fate and risk of microplastic in terrestrial ecosystems. PMID- 26852877 TI - Topologically protected Dirac plasmons and their evolution across the quantum phase transition in a (Bi(1-x)In(x))2Se3 topological insulator. AB - A 3D Topological Insulator (TI) is an intrinsically stratified electronic material characterized by an insulating bulk and Dirac free electrons at the interface with vacuum or another dielectric. In this paper, we investigate, through terahertz (THz) spectroscopy, the plasmon excitation of Dirac electrons on thin films of (Bi1-xInx)2Se3 TI patterned in the form of a micro-ribbon array, across a Quantum Phase Transition (QPT) from the topological to a trivial insulating phase. The latter is achieved by In doping onto the Bi-site and is characterized by massive electrons at the surface. While the plasmon frequency is nearly independent of In content, the plasmon width undergoes a sudden broadening across the QPT, perfectly mirroring the single particle (free electron) behavior as measured on the same films. This strongly suggests that the topological protection from backscattering characterizing Dirac electrons in the topological phase extends also to their plasmon excitations. PMID- 26852878 TI - Chemical characterization of fatty acids, alkanes, n-diols and alkyl esters produced by a mixed culture of Trichoderma koningii and Penicillium janthinellum grown aerobically on undecanoic acid, potatoe dextrose and their mixture. AB - Little is known about the mixed fungal synthesis of high-value aliphatics derived from the metabolism of simple and complex carbon substrates. Trichoderma koningii and Penicillium janthinellum were fed with undecanoic acid (UDA), potatoe dextrose broth (PDB), and their mixture. Pyrolysis Field Ionization Mass Spectrometry (Py-FIMS) together with (1)H and (13)C Nuclear Magnetic Resonance (NMR) characterized CHCl3 soluble aliphatics in the fungal cell culture. Data from NMR and Py-FIMS analysis were complementary to each other. On average, the mixed fungal species produced mostly fatty acids (28% of total ion intensity, TII) > alkanes (2% of TII) > n-diols (2% of TII) > and alkyl esters (0.8% of TII) when fed with UDA, PDB or UDA+PDB. The cell culture accumulated aliphatics extracellularly, although most of the identified compounds accumulated intracellularly. The mixed fungal culture produced high-value chemicals from the metabolic conversion of simple and complex carbon substrates. PMID- 26852879 TI - Programmable DNA scaffolds for spatially-ordered protein assembly. AB - Ever since the notion of using DNA as a material was realized, it has been employed in the construction of complex structures that facilitate the assembly of nanoparticles or macromolecules with nanometer-scale precision. Specifically, tiles fashioned from DNA strands and DNA origami sheets have been shown to be suitable as scaffolds for immobilizing proteins with excellent control over their spatial positioning. Supramolecular assembly of proteins into periodic arrays in one or more dimensions is one of the most challenging aspects in the design of scaffolds for biomolecular investigations and macromolecular crystallization. This review provides a brief overview of how various biomolecular interactions with high degree of specificity such as streptavidin-biotin, antigen-antibody, and aptamer-protein interactions have been used to fabricate linear and multidimensional assemblies of structurally intact and functional proteins. The use of DNA-binding proteins as adaptors, polyamide recognition on DNA scaffolds and oligonucleotide linkers for protein assembly are also discussed. PMID- 26852880 TI - Carpal tunnel syndrome: a common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. AB - BACKGROUND: Systemic wild-type ATTR (ATTRwt) amyloidosis is a prevalent aging related disorder. However, a limited number of systemic ATTRwt amyloidosis patients have been diagnosed antemortem, and therefore, the prevalence of ATTRwt is underestimated. Here, we investigated clinical findings of a series of systemic ATTRwt amyloidosis patients with antemortem diagnosis. METHODS: Thirty one consecutive patients diagnosed with systemic ATTRwt amyloidosis at Shinshu University Hospital were included in this study. Systemic ATTRwt amyloidosis was diagnosed based on proven ATTR amyloid deposition in biopsy specimens and confirmation of wild-type TTR genotype. RESULTS: The systemic ATTRwt amyloidosis patients consisted of 24 men and seven women, and mean age of onset was 69.8 +/- 9.0 years. The most common initial symptom was carpal tunnel syndrome (CTS, 17 patients), followed by heart failure symptoms (14 patients). The mean age at diagnosis was 74.5 +/- 8.3 years and the duration of illness from onset to diagnosis was 5.4 +/- 4.4 years. Cardiogenic embolism and renal dysfunction are also frequently seen during the course of the disease. CONCLUSIONS: CTS is the most common initial symptom of systemic ATTRwt amyloidosis. Our results suggest the possibility of systemic ATTRwt amyloidosis diagnosis at an early stage by carefully examining patients with CTS. PMID- 26852882 TI - Corrigendum. PMID- 26852881 TI - Elemental sulfur improves growth and phytoremediative ability of wheat grown in lead-contaminated calcareous soil. AB - Little is known about the effect of elemental sulfur on lead uptake and its toxicity in wheat. A pot experiment was conducted with the purpose to examine the impact of sulfur on improving Pb solubility in soil, and uptake and accumulation in wheat plants. The effect of three levels of lead (0, 50, and 100 mg/kg soil) and sulfur (0, 150, and 300 mmol/kg soil) was tested in all possible combinations. Root dry matter, straw, and grain yields, and the photosynthetic and transpiration rates decreased significantly with increase in the concentration of Pb in the soil. However, sulfur fertilization in the presence of Pb improved the photosynthetic and transpiration rates and consequently increased the straw and grain yields of wheat. It also enhanced Pb accumulation in roots, its translocation from roots to shoot, and accumulation in grain. S and Zn contents of different plant parts were also enhanced. Thus, by mitigating the toxic effect of Pb and improving wheat growth, sulfur enhances Pb accumulation by the aboveground plant parts and hence the phytoextraction capacity of wheat. However, total accumulation of Pb shows that wheat plant cannot be considered as a suitable candidate for phytoremediation. PMID- 26852883 TI - Valence states and possible charge ordering in LaCo(1-x)Rh(x)O3. AB - An unusual effect was discovered in Li et al (2010 J. Solid State Chem. 183 1388): the substitution of nonmagnetic low-spin Co(3+) in LaCoO3 by the formally isoelectronic and also nonmagnetic Rh(3+) led, surprisingly, to a rapid appearance of magnetism in LaCo(1-x)Rh(x)O3, even for small amounts of doping. Different explanations for this effect were proposed in the literature. To clarify the situation we carried out unbiased ab initio calculations of this system. We concluded that, in agreement with the original assumption of Li et al, but in contrast with later statements (Knizek et al 2012 Phys. Rev. B 85 134401), this effect is caused by the valence change ('redox reaction') Co(3+) + Rh(3+) > Co(2+) + Rh(4+), which creates magnetic Co(2+) and Rh(4+) ions. For the half filled case LaCo1/2Rh1/2O3 we obtained the state with charge ordering of Co(2+) and Rh(4+) ions, which according to our calculations are antiferromagnetically coupled. The obtained results reasonably explain the observed behavior of the magnetic susceptibility of LaCo(1-x)Rh(x)O3, and the novel state predicted at half-doping could be verified experimentally by detailed structural and magnetic studies and by x-ray absorption spectroscopy. PMID- 26852884 TI - Two-dimensional proton-detected (35)Cl/(1)H correlation solid-state NMR experiment under fast magic angle sample spinning: application to pharmaceutical compounds. AB - The determination of structure of hydrochloride salts of active pharmaceutical ingredients (HCl APIs) utilizing (35)Cl solid-state NMR studies has been of considerable interest in the recent past. Until now these studies relied on the (35)Cl direct observation method which has its own limitations in terms of the sensitivity and resolution due to the quadrupolar nature and the low gyromagnetic ratio of (35)Cl. In this contribution we demonstrate the two-dimensional (2D) (35)Cl/(1)H correlation measurement by using the proton detection-based (indirect observation of (35)Cl via(1)H) approach under fast magic angle sample spinning (MAS: 70 kHz). The main advantages of this approach over the direct observation method are highlighted in the present study. We have employed heteronuclear magnetization transfer through the recoupling of (35)Cl-(1)H heteronuclear dipolar interactions. The applicability of (35)Cl indirect detection method is first demonstrated on hydrochloride salts of amino acids, l-tyrosine.HCl and l histidine.HCl.H2O following which the 2D (35)Cl/(1)H correlations are obtained for HCl APIs, procainamide HCl (Proc) and aminoguanidine HCl (Amin). On the basis of separation between the central transition (CT) and satellite transition (ST) peaks, and the shape/width of CT powder patterns, it is also shown that the quadrupolar parameters which are useful for the elucidation of the molecular structure can be determined. Moreover, the (35)Cl/(1)H correlations provide the precise determination of (1)H chemical shifts of nearby (35)Cl nuclei. PMID- 26852886 TI - Makeup your mind: The impact of styling on perceived competence and warmth of female leaders. AB - Women are still underrepresented at the highest management levels. The think manager-think-male phenomenon suggests that leadership is associated with male rather than female attributes. Although styling has been shown to influence the evaluation of women's leadership abilities, the relevant specific features have been left remarkably unaddressed. In a 2 * 2 * 2 * 2 (skirt/pants, with/without jewelry, loose hair/braid, with/without makeup) between-subjects design, 354 participants evaluated a woman in a photograph. Women with makeup, pants, or with jewelry were rated as more competent than women without makeup, with skirts, or without jewelry. A combination of loose hair and no makeup was perceived as warmest, and women with loose hair were more likely to be hired than those with braids. In sum, even subtle changes in styling have a strong impact on how women's leadership abilities are evaluated. PMID- 26852885 TI - Effects of 12 weeks of combined training without caloric restriction on inflammatory markers in overweight girls. AB - The objective of the present study was to investigate the effects of combined training without caloric restriction on inflammatory markers in overweight girls. Thirty-three girls (13-17 years) were assigned into overweight training (n = 17) or overweight control (n = 16) groups. Additionally, a normal-weight group (n = 15) was used as control for the baseline values. The combined training programme consisted of six resistance exercises (three sets of 6-10 repetitions at 60-70% 1 RM) followed by 30 min of aerobic exercise (walking/running) at 50-80% VO2peak, performed in the same 60 min session, 3 days/weeks, for 12 weeks. Body composition, dietary intake, aerobic fitness (VO2peak), muscular strength (1 RM), glycaemia, insulinemia, lipid profile and inflammatory markers (C-reactive protein, interleukin-6, tumour necrosis factor-alpha, interleukin-10, leptin, resistin and adiponectin) were measured before and after intervention. There was a significant decrease in body fat (P < 0.01) and increase in fat-free mass (P < 0.01), VO2peak (P < 0.01), 1 RM for leg press (P < 0.01) and bench press (P < 0.01) in the overweight training group. Concomitantly, this group presented significant decreases in serum concentrations of C-reactive protein (P < 0.05) and leptin (P < 0.05), as well as in insulin resistance (P < 0.05) after the experimental period. In conclusion, 12 weeks of combined training without caloric restriction reduced inflammatory markers associated with obesity in overweight girls. PMID- 26852887 TI - Is early mobilisation better than immobilisation in the treatment of wrist sprains? AB - OBJECTIVE: Posttraumatic radial sided wrist pain is common and can represent a fracture or a ligament injury. However, in some patients radiographs and MRI are normal, indicating no specific diagnosis other than a wrist sprain. There is no consensus on the ideal treatment for this patient group. The aim was to investigate if patients with posttraumatic radial sided wrist pain and MRI not showing signs of fracture or SL-ligament injury should be treated with immediate mobilisation or 2 weeks cast immobilisation. METHOD: Forty-three patients, aged 18-64 years, were randomised to either a dorsal wrist cast for 2 weeks (n = 21), or immediate mobilisation (n = 22). Follow-up at 2, 4, and 6 weeks included clinical examination, self-assessment questionnaires (DASH, VAS), and recording of days on sick-leave. RESULTS: At 2 weeks patients treated in a cast had reduced wrist range of motion, ROM (77% vs 96%, p = 0.011), and higher DASH score (median 37 vs 18, p = 0.009) compared to patients treated with immediate mobilisation. At 4 weeks, DASH score was still higher in the group treated in a cast (median 14 vs 4, p = 0.01), but there was no difference in ROM. At 6 weeks there were no differences in any outcome measure between the groups. Furthermore, there was no significant difference in sick-leave between the groups (median 27 days vs 14 days, p = 0.077). CONCLUSION: Patients with radial sided wrist pain where MRI does not demonstrate fracture or SL ligament injury do not benefit from cast immobilisation and can be treated with early mobilisation. PMID- 26852888 TI - Should fetal scalp blood sampling be performed in the case of meconium-stained amniotic fluid? AB - OBJECTIVE: To investigate the effect of using fetal scalp blood sampling on the risk of neonatal respiratory distress syndrome (NRDS) with meconium-stained amniotic fluid (MSAF). METHODS: Prospective data collection with regard to MSAF during labor for low-risk term cephalic singleton live birth from 2012 to 2014. Maternal, obstetric and neonatal data were compared according to the occurrence of respiratory distress syndrome (RDS group) or not (no RDS group). RESULTS: Of 515 newborns born through MSAF, 46 experienced RDS and from them 10 experienced meconium aspiration syndrome. No difference was observed according to maternal characteristic, abnormal fetal heart rate tracing pattern irrespective of its category and cesarean rate. Apgar at one minute was lower in the group RDS (7.6 versus 8.5, p < 0.05). The mean umbilical artery pH values did not differ between the two groups. Significant difference between newborns with and without RDS in terms of fetal scalp lactate sampling during the labor (71.1% versus 55.1%, p < 0.05), and neonatal care unit (NCU) admissions (22.8% versus 10.8%, p < 0.05). Secondary rather than primary meconium was associated with RDS when performing fetal scalp blood assessment (p < 0.05). A significant correlation between RDS, fetal scalp blood assessment and MSAF diagnosed during the first stage of labor (after spontaneous rupture of membranes or at amniotomy) was found. CONCLUSION: In case of MSAF, fetal scalp blood sampling did not reduce the risk of RDS. PMID- 26852890 TI - A Call to Regulate Manufacture and Marketing of Blood Pressure Devices and Cuffs: A Position Statement From the World Hypertension League, International Society of Hypertension and Supporting Hypertension Organizations. PMID- 26852889 TI - Prenatal exposure to ethinylestradiol alters the morphologic patterns and increases the predisposition for prostatic lesions in male and female gerbils during ageing. AB - Ethinylestradiol (EE) is an endocrine disruptor (ED) which acts as an oestrogen agonist; this compound is known as an oral contraceptive. Male and female rodents exposed to EE during critical time points of development, such as in the prenatal period, show alterations in their reproductive tract during adulthood. Few studies have placed an emphasis on the effects of EE during ageing. Thus, this study had as it's objective the analysis of the morphological and immunohistochemical effects of exposure to EE in the prenatal period on ventral male prostate and female prostate of gerbils (Meriones unguiculatus) during ageing. The animals were exposed to EE (15 MUg/kg/day) during the 18-22th days of prenatal life (EE/PRE group), and the analyses were performed when the male and female reached 12 months of age. Our results showed an increase in the development of prostatic intraepithelial neoplasia (PIN), which was observed in the male and female prostate of EE/PRE groups. Immunohistochemistry showed a rise in prostatic epithelial and basal cells immunoreactivity, respectively, and to AR and p63 in the male EE/PRE. There were alterations in the morphological pattern of the prostatic glands and increase in predisposition to emergence of prostatic lesions of both sexes during ageing. Despite male and female having been exposed to the same doses of EE, the "exposure to EE promoted modifications" more accentuated in the male prostate. Thus the male gland is more sensitive to the action of this synthetic oestrogen than the female prostate. PMID- 26852891 TI - Flexible Structural Features of Pentafulvene Titanium Derivatives: Isolation and Characterization of NHC Complexes. AB - The reaction of eta(5),eta(1)-pentafulvene titanium complexes with the strong N heterocyclic carbene (NHC) donor 1,3,4,5-tetramethylimidazole-2-ylidene, leads to the formation of isolable NHC titanium adducts, featuring a haptotropic shift of the pentafulvene ligand, proved by single crystal X-ray diffraction as well as NMR spectroscopy studies. PMID- 26852893 TI - The Power of My. PMID- 26852892 TI - Cross-genotype-specific T-cell responses in acute hepatitis E virus (HEV) infection. AB - Hepatitis E is an inflammatory liver disease caused by infection with the hepatitis E virus (HEV). In tropical regions, HEV is highly endemic and predominantly mediated by HEV genotypes 1 and 2 with >3 million symptomatic cases per year and around 70 000 deaths. In Europe and America, the zoonotic HEV genotypes 3 and 4 have been reported with continues increasing new infections per year. So far, little is known about T-cell responses during acute HEV genotype 3 infection. Therefore, we did a comprehensive study investigating HEV-specific T cell responses using genotypes 3- and 1-specific overlapping peptides. Additional cytokines and chemokines were measured in the plasma. In four patients, longitudinal studies were performed. Broad functional HEV-specific CD4(+) and CD8(+) T-cell responses were detectable in patients acutely infected with HEV genotype 3. Elevated of pro- and anti-inflammatory cytokine levels during acute HEV infection correlated with ALT levels. Memory HEV-specific T-cell responses were detectable up to >1.5 years upon infection. Importantly, cross-genotype HEV specific T-cell responses (between genotypes 1 and 3) were measurable in all investigated patients. In conclusion, we could show for the first time HEV specific T-cell responses during and after acute HEV genotype 3 infection. Our data of cross-genotype HEV-specific T-cell responses might suggest a potential role in cross-genotype-specific protection between HEV genotypes 1 and 3. PMID- 26852894 TI - Effect of pregnancy on insulin requirements differs between type 1 and type 2 diabetes: A cohort study of 222 pregnancies. AB - BACKGROUND: Knowledge about expected insulin requirements during pregnancy, in women with pre-existing diabetes may assist clinicians to effectively respond to gestation-specific changes in glycemic pattern. Few studies have examined differences between type 1 (T1DM) and type 2 diabetes (T2DM). AIMS: To compare patterns of insulin requirements in pregnancy for women with pre-existing T1DM and T2DM. MATERIAL AND METHODS: A retrospective cohort study of 222 pregnancies was conducted in women with pre-existing diabetes, (67 with T1DM, 155 with T2DM). Total daily insulin dose (TID) at the end of each trimester, recorded as units and units per kilogram (median, 25th-75th percentile) as well as percentage increase in insulin dose per trimester were compared. RESULTS: Women with T1DM had higher insulin requirements in the first two trimesters than those with T2DM (0.69 (0.58-0.85) vs 0.36 (0.0-0.7) units/kg in first trimester; 0.80 (0.62-0.95) vs 0.61 (0.27-0.95) units/kg, P < 0.005) in second trimester), but requirements in late pregnancy were similar (0.97 (0.69-1.29) vs 0.95 (0.53-1.32) units/kg, P = 0.54). Women with T2DM needed much greater increases in insulin per trimester compared to T1DM (P < 0.001). Women with T1DM had a net fall in insulin requirements (3.7% in the first trimester and 4.1% in the late third trimester) while those with T2DM did not. CONCLUSIONS: This is the largest comparison study of insulin requirements in women with pre-existing diabetes, highlighting important trimester-specific differences between T1DM and T2DM to guide insulin titration during pregnancy. Our findings suggest a differential effect of pregnancy-mediated insulin resistance by type of diabetes. PMID- 26852895 TI - Overexpression of BCLXL in Osteoblasts Inhibits Osteoblast Apoptosis and Increases Bone Volume and Strength. AB - The Bcl2 family proteins, Bcl2 and BclXL, suppress apoptosis by preventing the release of caspase activators from mitochondria through the inhibition of Bax subfamily proteins. We reported that BCL2 overexpression in osteoblasts using the 2.3 kb Col1a1 promoter increased osteoblast proliferation, failed to reduce osteoblast apoptosis, inhibited osteoblast maturation, and reduced the number of osteocyte processes, leading to massive osteocyte death. We generated BCLXL (BCL2L1) transgenic mice using the same promoter to investigate BCLXL functions in bone development and maintenance. Bone mineral density in the trabecular bone of femurs was increased, whereas that in the cortical bone was similar to that in wild-type mice. Osteocyte process formation was unaffected and bone structures were similar to those in wild-type mice. A micro-CT analysis showed that trabecular bone volume in femurs and vertebrae and the cortical thickness of femurs were increased. A dynamic bone histomorphometric analysis revealed that the mineralizing surface was larger in trabecular bone, and the bone-formation rate was increased in cortical bone. Serum osteocalcin but not TRAP5b was increased, BrdU-positive osteoblastic cell numbers were increased, TUNEL-positive osteoblastic cell numbers were reduced, and osteoblast marker gene expression was enhanced in BCLXL transgenic mice. The three-point bending test indicated that femurs were stronger in BCLXL transgenic mice than in wild-type mice. The frequency of TUNEL-positive primary osteoblasts was lower in BCLXL transgenic mice than in wild-type mice during cultivation, and osteoblast differentiation was enhanced but depended on cell density, indicating that enhanced differentiation was mainly owing to reduced apoptosis. Increased trabecular and cortical bone volumes were maintained during aging in male and female mice. These results indicate that BCLXL overexpression in osteoblasts increased the trabecular and cortical bone volumes with normal structures and maintained them majorly by preventing osteoblast apoptosis, implicating BCLXL as a therapeutic target of osteoporosis. (c) 2016 American Society for Bone and Mineral Research. PMID- 26852896 TI - Superelastic, Macroporous Polystyrene-Mediated Graphene Aerogels for Active Pressure Sensing. AB - Three-dimensional (3D) graphene-based polymer/graphene aerogels with excellent mechanical properties are crucial for broad applications. The creation of such polymer/graphene aerogels remains challenging because of the poor dispersion and compatibility of polymer within the graphene matrix. By using the freezing directed assembly of graphene under the assistance of surfactant, 3D macroporous polystyrene/graphene aerogels (MPS-GAs) with lightweight, superelastivity (80 % strain), high strength (80 kPa), and good electrical properties have been achieved in this study. The as-prepared MPS-GAs shows excellent electromechanical performance with stable cyclic resilient properties and sensitive resistance responses, thus making the MPS-GAs promising candidates for applications in actuators, elastic conductors, strain/pressure sensors, and wearable devices. PMID- 26852897 TI - Effects of quebracho tannin extract and activated charcoal on nutrient digestibility, digesta passage and faeces composition in goats. AB - Irrigation agriculture of hot climates suffers from rapid soil organic carbon (C) turnover, high nitrogen (N) leaching and gaseous losses. In this context, we explored the possibility of supplementing ruminants with activated charcoal (AC) and condensed tannins (CT) to increase faecal concentration of long-lived C and slowly decomposable N. For this purpose, we fed AC and quebracho tannin extract (QTE, source of CT) to goats and determined nutrient digestibility, digesta passage and composition of faeces. The feeding trial comprised three periods, with 24 male goats assigned to five treatments and a control. On dry matter (DM) basis, the basal diet (control) consisted of 50% hay, 46.5% crushed maize and 3.5% soya bean meal. Treatment diets contained (on DM basis) 2% and 4% QTE (QTE2, QTE4), 1.5% and 3.0% AC (AC1.5, AC3.0) and a mixture of 2% QTE plus 1.5% AC (QTEAC). Samples of feed, refusals and faeces were analysed for chemical constituents; digesta passage was computed with a one-compartment Gamma-2 model from pulse-dose application of ytterbium-mordanted fibre and quantitative collection of faeces during 7 days. Compared to the control, organic matter and N digestibility were reduced with QTE2 and QTE4 (p <= 0.001), that of neutral and acid detergent fibre (NDFom, ADFom) decreased with QTE4, QTEAC and both AC treatments (p <= 0.001). Ruminal particle passage ranged from 0.051 h-1 (QTEAC) to 0.056 h-1 (control; p > 0.05). Apart from the correlation between total tract mean retention time and faecal C/N ratio (r = -0.35), passage parameters did not affect faeces quality. While faecal N concentration was not altered by both additives, AC enhanced faecal NDFom, ADFom and C concentrations (p <= 0.001). Whereas feeding up to 3% AC might slow down the decomposition of manure in the field without negatively affecting the digestive physiology of goats, including QTE seems not advantageous from a physiological and nutrient recycling perspective. PMID- 26852898 TI - Hemidiaphragm atrophy in muscle-specific kinase myasthenia gravis. PMID- 26852899 TI - Pulse photodynamic therapy reduces inflammation without compromising efficacy in the treatment of multiple mild actinic keratoses of the face and scalp: a randomized clinical trial. AB - BACKGROUND: The main side-effects of photodynamic therapy (PDT) for actinic keratoses (AKs) are post-treatment erythema and oedema, and pain during illumination. Severe erythema after PDT enhances the down time associated with the treatment. OBJECTIVES: To evaluate in a randomized intraindividual study whether pulse-PDT and corticosteroid pulse-PDT would reduce treatment-induced erythema compared with conventional PDT. METHODS: Twenty-two patients with multiple mild AKs on the face and scalp were treated with methyl aminolaevulinate (MAL)-PDT in three similar areas. Two areas were incubated with MAL for 30 min (pulse-PDT) and one area was incubated with MAL for 3 h (conventional PDT). All areas were illuminated with red light after 3 h. In one of the pulse-PDT areas a superpotent corticosteroid was applied before and just after PDT (S-pulse-PDT). RESULTS: Pulse-PDT significantly reduced PDT-induced erythema (P = 0.020), and erythema was even further reduced by S-pulse-PDT (P < 0.001). The complete lesion response rate 3 months after PDT did not differ significantly between the three treated areas. CONCLUSIONS: Pulse-PDT and S-pulse-PDT reduced erythema 24 h after treatment of multiple mild AKs on the face and scalp. The use of a short MAL application time and topical corticosteroid did not affect the efficacy of PDT and may be an easy way to make PDT treatment of large visible areas more acceptable. PMID- 26852900 TI - Editorial--Indomethacin. PMID- 26852901 TI - Margins for cervical and vulvar cancer. AB - Surgery is the primary treatment for vulvar cancer as well as early-stage carcinoma of the cervix. This article reviews the significance of margin status after surgery on overall survival, need for further surgical intervention, and role for possible adjuvant therapy. It summarizes the abundant literature on margin status in vulvar cancer and highlights the need for further investigation on the prognostic significance of margins in cervical cancer. In addition, it reviews other important operative considerations. PMID- 26852902 TI - An exploration of integrated data on the social dynamics of suicide among women. AB - The gender-based nature of suicide-related behaviour is largely accepted. However, studies that report exclusively on female suicides are rare. Here we demonstrate how female suicide has effectively been 'othered' and appears incidental in studies which compare female and male behaviour. We highlight how recent studies of suicide have tended to be dominated by male-only approaches, which increasingly link issues of masculinity with male death by suicide. Drawing on data collected from the general practitioner and coroner's office, we then apply the sociological autopsy approach to a cohort of 78 deaths recorded as suicides in the UK between 2007 and 2009. By focusing on females in isolation from males, we demonstrate that, as in male-only suicide studies, it is similarly possible to draw out issues associated with the feminine identity, which can be linked to death by suicide. We find that bereavement, sexual violence and motherhood could all be linked to the lives and help-seeking of the females who died. In closing, we suggest that a reorientation towards sociological analytic approaches of female suicide may help to produce further reductions in the rate of female death by suicide. A Virtual Abstract of this paper can be found at: https://www.youtube.com/watch?v=a0w9KKMFdIQ. PMID- 26852903 TI - Photochemistry of Wild-Type and N378D Mutant E. coli DNA Photolyase with Oxidized FAD Cofactor Studied by Transient Absorption Spectroscopy. AB - DNA photolyases (PLs) and evolutionarily related cryptochrome (CRY) blue-light receptors form a widespread superfamily of flavoproteins involved in DNA photorepair and signaling functions. They share a flavin adenine dinucleotide (FAD) cofactor and an electron-transfer (ET) chain composed typically of three tryptophan residues that connect the flavin to the protein surface. Four redox states of FAD are relevant for the various functions of PLs and CRYs: fully reduced FADH(-) (required for DNA photorepair), fully oxidized FADox (blue-light absorbing dark state of CRYs), and the two semireduced radical states FAD(.-) and FADH(.) formed in ET reactions. The PL of Escherichia coli (EcPL) has been studied for a long time and is often used as a reference system; however, EcPL containing FADox has so far not been investigated on all relevant timescales. Herein, a detailed transient absorption study of EcPL on timescales from nanoseconds to seconds after excitation of FADox is presented. Wild-type EcPL and its N378D mutant, in which the asparagine facing the N5 of the FAD isoalloxazine is replaced by aspartic acid, known to protonate FAD(.-) (formed by ET from the tryptophan chain) in plant CRYs in about 1.5 MUs, are characterized. Surprisingly, the mutant protein does not show this protonation. Instead, FAD(.-) is converted in 3.3 MUs into a state with spectral features that are different from both FADH(.) and FAD(.-) . Such a conversion does not occur in wild-type EcPL. The chemical nature and formation mechanism of the atypical FAD radical in N378D mutant EcPL are discussed. PMID- 26852904 TI - Safety, pharmacokinetics and pharmacodynamics of GLPG0974, a potent and selective FFA2 antagonist, in healthy male subjects. AB - AIMS: Free fatty acids (FFA) can act as direct signalling molecules through activation of several membrane-bound G-protein coupled receptors. The FFA2 receptor (known as GPR43) is activated by short chain fatty acids (SCFA) such as acetate and has been shown to play a major role in SCFA-induced neutrophil activation and migration and to contribute in the development and control of inflammation. GLPG0974 is a potent and selective antagonist of the human FFA2. The main objectives of the two phase 1 trials were to characterize the safety, tolerability, pharmacokinetics and pharmacodynamics of GLPG0974. METHODS: Two consecutive randomized, double-blind, placebo-controlled, single centre trials in healthy subjects were performed. In the first, GLPG0974 was administered as single doses up to 250 mg and in the second, multiple daily doses up to 400 mg for 14 days were evaluated. Non-compartmental analysis was used to determine GLPG0974 pharmacokinetics while target engagement was investigated through the inhibition of neutrophils in acetate-simulated whole blood samples using surface expression of CD11b activated epitope as a marker of neutrophil activation. RESULTS: The investigation of safety/tolerability and pharmacokinetics in the early development phase showed that GLPG0974 was safe and well tolerated up to a daily dose of 400 mg. GLPG0974 showed good and dose proportional exposure up to 400 mg daily as well as a substantial and sustained inhibition of acetate stimulated neutrophil activation. CONCLUSION: Based on these results, a proof-of concept study was initiated to evaluate the safety, tolerability and efficacy of GLPG0974 in patients with mild to moderate ulcerative colitis. PMID- 26852905 TI - Neural substrates of the 'low-level' system for speech articulation: Evidence from primary opercular syndrome. AB - We describe a patient with progressive disorder of speech, without language impairment (opercular syndrome). Morphometric analysis confirmed asymmetric volume reduction of the precentral areas (>left). Diffusion imaging showed significant white matter changes in the left frontal lobe, with specific involvement of the left corticobulbar tract and connections between supplementary/pre-supplementary motor areas and the frontal operculum (frontal aslant tract). We suggest that the organization of expressive language includes a 'low level' motor system principally distributed in the left hemisphere that shows specific susceptibility to neurodegeneration, distinct from neural systems subtending praxic, and cognitive aspects of language. PMID- 26852906 TI - Association of copy number polymorphisms at the promoter and translated region of COMT with Japanese patients with schizophrenia. AB - Chromosome 22q11.2 deletion syndrome and genetic variations including single nucleotide polymorphism (SNP) and copy number variation (CNV) in catechol-O methyltransferase (COMT) situated at 22q11.2 remains controversial. Here, the genetic relationship between COMT and Japanese patients with schizophrenia was investigated by examining whether the SNPs correlated with schizophrenia based on a common disease-common variant hypothesis. Additionally, 22q11.2DS were screened based on a common disease-rare variant hypothesis; low-frequency CNVs situated at two COMT promoters and exons were investigated based on the low-frequency variants with an intermediate effect; and positive findings from the first stage were reconfirmed using a second-stage replication study including a larger sample size. Eight SNPs and 10 CNVs were investigated using Taqman SNP and CNV quantitative real-time polymerase chain reaction method. For the first-stage analysis, 513 unrelated Japanese patients with schizophrenia and 705 healthy controls were examined. For the second-stage replication study, positive findings from the first stage were further investigated using a larger sample size, namely 1,854 patients with schizophrenia and 2,137 controls. The first-stage analysis showed significant associations among schizophrenia, intronic SNP rs165774, CNV6 situated at promoter 1, CNV8 at exon 6, and CNV9 at exon 7. The second-stage study showed that intronic SNP rs165774 (chi(2) = 8.327, P = 0.0039), CNV6 (chi(2) = 19.66, P = 0.00005), and CNV8 (chi(2) = 16.57, P = 0.00025) were significantly associated with schizophrenia. Large and rare CNVs as well as low frequency CNVs and relatively small CNVs, namely <30 kb in COMT, may be genetic risk factors for schizophrenia. PMID- 26852907 TI - Into rather unexplored terrain-transcellular transport across the blood-brain barrier. AB - Efficient neuronal signaling in the central nervous system strictly depends on a well-balanced microenvironment around glial cells, synapses, and axons. Unique features of the blood-brain barrier (BBB) endothelium largely determine the composition of this micro-milieu and are dependent on the tight interplay with surrounding astrocytes and pericytes. BBB endothelial cells are endowed with a highly restrictive junctional complex that occludes the intercellular cleft, thereby preventing paracellular diffusion. The paracellular pathway is subject to extensive research as integrity loss of the junctional complex is associated with many neuropathologies, inflammation, and edema. Another important feature of the BBB endothelium is the low prevalence of nonspecific, transcytotic events, including (macro)pinocytosis, clathrin-dependent and caveolin-dependent endocytosis and the subsequent trafficking of vesicles to the opposite membrane. Although less studied, evidence is accruing that this pathway importantly contributes to increased BBB permeability, often when the junctional complex remains intact. Here, we review current knowledge on the contribution of the transcellular pathway to the BBB leak observed in different pathologic conditions. In addition, we hypothesize that nonselective, large pore connexin and pannexin channels may contribute to transcellular transport, either by providing a direct diffusion pathway across the endothelial monolayer, or indirectly, by exerting control over intracellular levels of the signaling ion Ca(2+) that is involved in many steps of the vesicular pathway. We conclude that transcytotic events at the BBB, despite being less acknowledged, cannot be simply dismissed as done in the past, but actively contribute to BBB leakage in many different pathologies. GLIA 2016;64:1097-1123. PMID- 26852909 TI - Erratum. PMID- 26852908 TI - Clinical Outcomes of Single- versus Dual-Chamber Implantable Cardioverter Defibrillators: Lessons from the Israeli ICD Registry. AB - OBJECTIVE: To compare the clinical outcomes of a single- versus dual-chamber ICD for primary prevention of sudden cardiac death in a large, national ICD registry. METHODS: Data were collected from the prospective Israeli ICD Registry. Baseline characteristics and clinical outcomes including mortality, admissions for heart failure (HF), and ICD therapy were compared between the two groups. RESULTS: A total of 1,125 subjects, 37% with a single-chamber and 63% with a dual-chamber ICD, constructed the baseline cohort. Approximately 80% had ischemic heart disease (IHD). Mean follow-up was 22 months, mean ejection fraction was 30%, and mean QRS width was 103 milliseconds in both groups. During follow-up, there were no significant differences in the rate of mortality, admissions for HF, appropriate or inappropriate therapy, or in time to any of the clinical outcomes. Using multivariate analysis, single-chamber ICD was not associated with increased risk of death or admission for HF. In a subgroup of patients with IHD, single chamber ICD was associated with a higher rate of inappropriate therapy. CONCLUSIONS: In this large retrospective population-based cohort, dual-chamber ICD showed no benefit in reducing the incidence of death or HF admissions, whereas in a subgroup of patients with IHD, single-chamber ICD was associated with increased inappropriate therapy. Further prospective studies are necessary to assess the benefit of dual-chamber ICD in reducing the rate of inappropriate therapy. PMID- 26852910 TI - Variant of PBX2 gene in the 6p21.3 asthma susceptibility locus is associated with allergic rhinitis in Chinese subjects. AB - BACKGROUND: Allergic rhinitis (AR) is a complex chronic inflammatory disease of the nasal mucosa, caused by an interaction between genetic and environmental factors. As evidence suggests that some genetic variants may increase susceptibility to both AR and asthma, the objective of this study was to identify asthma susceptibility variants associated with AR in the Chinese population. METHODS: A cohort of 402 individuals with physician-diagnosed AR and 416 healthy controls were recruited from the Han Chinese population in Beijing. DNA was extracted from the peripheral blood and a total of 12 single-nucleotide polymorphisms (SNPs) shown to be associated with asthma in Japanese subjects were selected for genotyping using the SequenomMassARRAY technology platform. RESULTS: Analysis of frequency differences of allele between the AR patients and control subjects showed that the C allele of rs204993 in the pre-B-cell leukemia homeobox 2 (PBX2) gene from the 6p21.3 locus was significantly associated with AR (p = 0.0006, pcorrected = 0.0340). Genotype analysis further confirmed the difference in distribution of this variant between AR patients and controls in the both the dominant (pT/C+C/C vs T/T = 7.37*10(-5) ) and co-dominant (pT/C vs T/T = 1.98 * 10(-4) , pC/C vs T/T = 0.004) models. CONCLUSION: These results suggest that the PBX2 gene in the 6p21.3 asthma susceptibility locus may be associated with increased risk for both AR and asthma in Chinese subjects. PMID- 26852911 TI - Prospective study of the hemodynamic behavior of ophthalmic arteries in postpartum preeclamptic women: A doppler evaluation. AB - The aim of this study was to evaluate the hemodynamic behavior of the ophthalmic artery by means of the Doppler ultrasound, in postpartum preeclamptic women. It was an observational prospective study with 44 postpartum preeclamptic women (group 1) and 49 postpartum normal women with normal blood pressure and with no previous illnesses known (group 2). All the pregnant women had a Doppler ultrasound exam of the ophthalmic artery in the immediate puerperium, that is, 10 days for the delivery (time 1). Group 1 was then followed prospectively, 26 patients of which returned to the last test in the remote puerperium in 45 days (time 2) and 29 patients returned to the last test in the remote puerperium in 90 days (time 3). All these women had preeclampsia before the delivery. The resistance index (RI), pulsatility index (PI), peak systolic velocity (PSV), end diastolic flow velocity (EDV), second peak of systolic velocity (P2), and the peak ratio (PR) were calculated. The data obtained are expressed in average and standard deviation, by using the Lilliefors test for normality. The average of the Doppler indexes in groups 1 and 2 was compared by means of test t of the student. Group 1 was analyzed separately, comparing the three times, using the test of ANOVA for repetitive measures and Tukey post-hoc range test. In the "Results" section, the statically meaningful differences in RI, PI, P2, RPV, and EDV (p < 0.0001, p < 0.0001, p < 0.0009, p < 0.0001, p < 0.0028) were found in the immediate puerperium of group 1 in relation to group 2, indicating the persistence of hyperperfusion and orbital vasodilatation in the immediate postpartum period in patients who had complicated pregnancies previously due to preeclampsia. In the evolutionary analysis of group 1, comparing the Doppler indexes between the immediate and late puerperium, statistically relevant differences between the rates of RI, P2, and PR (p < 0,01) were observed, showing a raise of RI and reduction of P2 and PR, and also a tendency of normalization of these rates in the late puerperium. When the same indexes were compared (PI, P2, and PR) now in times 2 and 3, the remote, and late puerperium, respectively, there were no significant differences, indicating the stabilization of these indexes since the 45th day of the puerperium. Within 90 days, RI, PI, and PR are not stabilized yet in relation to the control, even though there is a tendency of these indexes to reach the control. In conclusion, there was persistence of signs of vasodilatation and hyperperfusion of the orbital territory, represented by Doppler of the ophthalmic artery in the immediate puerperium of preeclamptic women. A tendency of normalization of the orbital hemodynamic standard in the pregnant women from the period of the late puerperium was observed, but there was no complete normalization of the vascular pattern on the remote postpartum. PMID- 26852912 TI - Therapeutic potential of dairy bioactive peptides: A contemporary perspective. AB - Dairy products are associated with numerous health benefits. These are a good source of nutrients such as carbohydrates, protein (bioactive peptides), lipids, minerals, and vitamins, which are essential for growth, development, and maintenance of the human body. Accordingly, dairy bioactive peptides are one of the targeted compounds present in different dairy products. Dairy bioactive compounds can be classified as antihypertensive, anti-oxidative, immmunomodulant, anti-mutagenic, antimicrobial, opoid, anti-thrombotic, anti-obesity, and mineral binding agents, depending upon biological functions. These bioactive peptides can easily be produced by enzymatic hydrolysis, and during fermentation and gastrointestinal digestion. For this reason, fermented dairy products, such as yogurt, cheese, and sour milk, are gaining popularity worldwide, and are considered excellent source of dairy peptides. Furthermore, fermented and non fermented dairy products are associated with lower risks of hypertension, coagulopathy, stroke, and cancer insurgences. The current review article is an attempt to disseminate general information about dairy peptides and their health claims to scientists, allied stakeholders, and, certainly, readers. PMID- 26852913 TI - Imatinib mesylate in chronic myeloid leukemia: frontline treatment and long-term outcomes. AB - The tyrosine kinase inhibitor Imatinib Mesylate has dramatically improved the clinical outcome of chronic myeloid leukemia (CML) patients in the chronic phase of the disease, generating unprecedented rates of complete hematologic and cytogenetic responses and sustained reductions in BCR-ABL transcripts. Here, we present an overview on the efficacy and safety of Imatinib and describe the most important clinical studies employing this drug for the frontline treatment of chronic phase CML. We also discuss recent reports describing the long-term outcome of patients receiving Imatinib for their disease. The imminent availability of generic forms of Imatinib coupled with the approval of expensive second-generation tyrosine kinase inhibitors underlines an unmet need for early molecular parameters that may distinguish CML patients likely to benefit from the drug from those that should receive alternative forms of treatment. PMID- 26852914 TI - A life in error. PMID- 26852915 TI - Two sides of the same coin: Xyloglucan endotransglucosylases/hydrolases in host infection by the parasitic plant Cuscuta. AB - The holoparasitic angiosperm Cuscuta develops haustoria that enable it to feed on other plants. Recent findings corroborate the long-standing theory that cell wall modifications are required in order for the parasite to successfully infect a host, and further suggest that changes to xyloglucan through the activity of xyloglucan endotransglucosylases/hydrolases (XTHs) are essential. On the other hand, XTH expression was also detected in resistant tomato upon an attack by Cuscuta, which suggests that both host and parasite use these enzymes in their "arms race." Here, we summarize existing data on the cell wall-modifying activities of XTHs during parasitization and present a model suggesting how XTHs might function to make the host's resources accessible to Cuscuta. PMID- 26852916 TI - Is Ovarian Preservation Feasible in Early-Stage Adenocarcinoma of the Cervix? AB - BACKGROUND In cervical adenocarcinoma, surgical treatment involves bilateral oophorectomy, which affects the long-term quality of life. The aim of our study was to access the incidence of ovarian metastasis in early-stage cervical adenocarcinoma and to suggest an algorithm for the triage of these patients to preserve the ovaries. MATERIAL AND METHODS A total 101 patients with cervical adenocarcinoma who had undergone radical hysterectomy with pelvic lymphadenectomy and bilateral oophorectomy were included in this study. Data on the clinicopathologic characteristics of the cases were collected and low risk factors for ovarian metastasis in early-stage cervical adenocarcinoma were analyzed. RESULTS The ovary metastasis rate of cervical adenocarcinoma in this study was 4.95%, while it is only 2% in stage IB1. Pathological grade, LSVI, lymph node status, tumor size, depth of stromal invasion, and involvement of the junction of the cervix and the body of the uterus were associated with ovarian metastasis, while LSVI, lymph node status, depth of stromal invasion, and involvement of the junction of the cervix and the body of the uterus were associated with ovarian metastasis in stage IB. Multivariate analysis revealed that LVSI and lymph node metastasis were independent risk factors for ovarian metastasis in all stages of cervical adenocarcinoma, but involvement of the junction of the cervix and the body of the uterus was an independent risk factor for ovarian metastasis in stage IB. CONCLUSIONS The incidence of ovarian metastasis in cervical adenocarcinoma is low. Our study suggests that ovarian preservation is safe and feasible in patients with no risk factors for ovarian metastasis. Further prospective studies are warranted. PMID- 26852917 TI - Role of autophagy in cadmium-induced apoptosis of primary rat osteoblasts. AB - Cadmium (Cd) is a common environmental pollutant that can damage many organs and the fetus. We previously reported that Cd induced apoptosis in primary rat osteoblasts (OBs). OB apoptosis induced by Cd will eventually lead to osteoporosis. In this study, a novel pharmacotherapeutic approach was investigated involving the regulation of autophagy to prevent Cd osteoporosis. The results showed that Cd treatment induced apoptosis in OBs, as demonstrated by the ratio of Bax/Bcl-2, activation of poly (ADP-ribose) polymerase (PARP) and nuclear condensation. In addition, cells treated with Cd were observed to undergo autophagic cell death by monitoring the induction of the beclin 1, autophagy gene 5 (Atg5) and the expression of microtubule-associated protein 1 light chain 3 (LC3). The results indicated that promotion of apoptotic cell death by Cd is accompanied by induction of autophagy in OBs. Interestingly, Cd-mediated apoptotic cell death was suppressed by pretreatment with the autophagy activator rapamycin (RAP) and potentiated by the autophagy inhibitor chloroquine (CQ) or small interfering RNA against beclin 1. These findings suggest that the autophagic response plays a protective role that impedes eventual cell death. Activation of autophagy could therefore be an adjunctive strategy for treatment of Cd-induced osteoporosis. PMID- 26852918 TI - Aryl Hydrocarbon Receptor Activates NDRG1 Transcription under Hypoxia in Breast Cancer Cells. AB - Hypoxia has been intensively investigated over the past several decades based on the observations that hypoxic tumors are more resistant to therapy and have a worse prognosis. Previously, we reported that N-myc downstream-regulated gene 1 (NDRG1) is strongly up-regulated under hypoxia and may play an important role in tumor adaptation to fluctuating oxygen concentrations. However, the regulatory mechanism of NDRG1 under hypoxia remains elusive. Therefore, the purpose of this study was to identify the transcription factors that regulate NDRG1 and to investigate the functional roles of NDRG1 in hypoxia. We showed that binding sites of aryl hydrocarbon receptor (AHR) were predicted in the NDRG1 promoter. Nuclear AHR was up-regulated in the presence of cobalt and hypoxia. AHR translocated to nuclei and bound between base pairs -412 and -388 of the NDRG1 promoter in hypoxia. Moreover, hypoxia-mimetic induction of NDRG1 was attenuated by knockdown of AHR expression. Also, overexpression of AHR facilitated cell proliferation and migration via up-regulation of NDRG1. These results showed for the first time that AHR positively regulates NDRG1 transcription through an AHR binding site by way of hypoxia-mimetic signaling, which may lead to development of a specific therapeutic regimen to prevent tumor malignancy under hypoxia. PMID- 26852919 TI - Scarce evidence of the causal role of germline mutations in UNC5C in hereditary colorectal cancer and polyposis. AB - Germline mutations in UNC5C have been suggested to increase colorectal cancer (CRC) risk, thus causing hereditary CRC. However, the evidence gathered thus far is insufficient to include the study of the UNC5C gene in the routine genetic testing of familial CRC. Here we aim at providing a more conclusive answer about the contribution of germline UNC5C mutations to genetically unexplained hereditary CRC and/or polyposis cases. To achieve this goal we sequenced the coding region and exon-intron boundaries of UNC5C in 544 familial CRC or polyposis patients (529 families), using a technique that combines pooled DNA amplification and massively parallel sequencing. A total of eight novel or rare variants, all missense, were identified in eight families. Co-segregation data in the families and association results in case-control series are not consistent with a causal effect for 7 of the 8 identified variants, including c.1882_1883delinsAA (p.A628K), previously described as a disease-causing mutation. One variant, c.2210G > A (p.S737N), remained unclassified. In conclusion, our results suggest that the contribution of germline mutations in UNC5C to hereditary colorectal cancer and to polyposis cases is negligible. PMID- 26852920 TI - Role of the Pinning Points in epitaxial Graphene Moire Superstructures on the Pt(111) Surface. AB - The intrinsic atomic mechanisms responsible for electronic doping of epitaxial graphene Moires on transition metal surfaces is still an open issue. To better understand this process we have carried out a first-principles full characterization of the most representative Moire superstructures observed on the Gr/Pt(111) system and confronted the results with atomically resolved scanning tunneling microscopy experiments. We find that for all reported Moires the system relaxes inducing a non-negligible atomic corrugation both, at the graphene and at the outermost platinum layer. Interestingly, a mirror "anti-Moire" reconstruction appears at the substrate, giving rise to the appearance of pinning-points. We show that these points are responsible for the development of the superstructure, while charge from the Pt substrate is injected into the graphene, inducing a local n-doping, mostly localized at these specific pinning-point positions. PMID- 26852922 TI - Spectroscopy of carrier multiplication in nanocrystals. AB - Carrier multiplication in nanostructures promises great improvements in a number of widely used technologies, among others photodetectors and solar cells. The decade since its discovery was ridden with fierce discussions about its true existence, magnitude, and mechanism. Here, we introduce a novel, purely spectroscopic approach for investigation of carrier multiplication in nanocrystals. Applying this method to silicon nanocrystals in an oxide matrix, we obtain an unambiguous spectral signature of the carrier multiplication process and reveal details of its size-dependent characteristics-energy threshold and efficiency. The proposed method is generally applicable and suitable for both solid state and colloidal samples, as well as for a great variety of different materials. PMID- 26852921 TI - Colorectal cancer characterization and therapeutic target prediction based on microRNA expression profile. AB - Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer death. However, the molecular mechanisms underlying CRC initiation, growth and metastasis are poorly understood. In this study, based on our previous work for comprehensively analyzing miRNA sequencing data, we examined a series of colorectal cancer microRNAs expression profiles data. Results show that all these CRC samples share the same four pathways including TGF-beta signaling pathway, which is important in colorectal carcinogenesis. Twenty-one microRNAs that evolved in the four overlapped pathways were then discovered. Further analysis selected miR-21 as an important regulator for CRC through TGF-beta pathways. This study develops methods for discovering tumor specific miRNA cluster as biomarker and for screening new cancer therapy targets based on miRNA sequencing. PMID- 26852923 TI - Mesenchymal stem cell-based therapy in kidney transplantation. AB - Kidney transplantation is the best treatment for end-stage renal disease, but its implementation is limited by organ shortage and immune rejection. Side effects of current immunosuppressive drugs, such as nephrotoxicity, opportunistic infection, and tumorigenic potential, influence long-term graft outcomes. In recent years, continued research and subsequent discoveries concerning the properties and potential utilization of mesenchymal stem cells (MSCs) have aroused considerable interest and expectations. Biological characteristics of MSCs, including multi lineage differentiation, homing potential, paracrine effect and immunomodulation, have opened new horizons for applications in kidney transplantation. However, many studies have shown that the biological activity of MSCs depends on internal inflammatory conditions, and the safety and efficacy of the clinical application of MSCs remain controversial. This review summarizes the findings of a large number of studies and aims to provide an objective viewpoint based on a comprehensive analysis of the presently established benefits and obstacles of implementing MSC-based therapy in kidney transplantation, and to promote its clinical translation. PMID- 26852924 TI - Exploration of Novel Botanical Insecticide Leads: Synthesis and Insecticidal Activity of beta-Dihydroagarofuran Derivatives. AB - The discovery of novel leads and new mechanisms of action is of vital significance to the development of pesticides. To explore lead compounds for botanical insecticides, 77 beta-dihydroagarofuran derivatives were designed and synthesized. Their structures were mainly confirmed by (1)H NMR, (13)C NMR, DEPT 135 degrees , IR, MS, and HRMS. Their insecticidal activity was evaluated against the third-instar larvae of Mythimna separata Walker, and the results indicated that, of these derivatives, eight exhibited more promising insecticidal activity than the positive control, celangulin-V. Particularly, compounds 5.7, 6.6, and 6.7 showed LD50 values of 37.9, 85.1, and 21.1 MUg/g, respectively, which were much lower than that of celangulin-V (327.6 MUg/g). These results illustrated that beta-dihydroagarofuran ketal derivatives can be promising lead compounds for developing novel mechanism-based and highly effective botanical insecticides. Moreover, some newly discovered structure-activity relationships are discussed, which may provide some important guidance for insecticide development. PMID- 26852925 TI - Rapid radiation in bacteria leads to a division of labour. AB - The division of labour is a central feature of the most sophisticated biological systems, including genomes, multicellular organisms and societies, which took millions of years to evolve. Here we show that a well-organized and robust division of labour can evolve in a matter of days. Mutants emerge within bacterial colonies and work with the parent strain to gain new territory. The two strains self-organize in space: one provides a wetting polymer at the colony edge, whereas the other sits behind and pushes them both along. The emergence of the interaction is repeatable, bidirectional and only requires a single mutation to alter production of the intracellular messenger, cyclic-di-GMP. Our work demonstrates the power of the division of labour to rapidly solve biological problems without the need for long-term evolution or derived sociality. We predict that the division of labour will evolve frequently in microbial populations, where rapid genetic diversification is common. PMID- 26852927 TI - Metabolic bridge between microbiota and humans. PMID- 26852926 TI - Intestinal Microbiota Distinguish Gout Patients from Healthy Humans. AB - Current blood-based approach for gout diagnosis can be of low sensitivity and hysteretic. Here via a 68-member cohort of 33 healthy and 35 diseased individuals, we reported that the intestinal microbiota of gout patients are highly distinct from healthy individuals in both organismal and functional structures. In gout, Bacteroides caccae and Bacteroides xylanisolvens are enriched yet Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum depleted. The established reference microbial gene catalogue for gout revealed disorder in purine degradation and butyric acid biosynthesis in gout patients. In an additional 15-member validation-group, a diagnosis model via 17 gout associated bacteria reached 88.9% accuracy, higher than the blood-uric-acid based approach. Intestinal microbiota of gout are more similar to those of type-2 diabetes than to liver cirrhosis, whereas depletion of Faecalibacterium prausnitzii and reduced butyrate biosynthesis are shared in each of the metabolic syndromes. Thus the Microbial Index of Gout was proposed as a novel, sensitive and non-invasive strategy for diagnosing gout via fecal microbiota. PMID- 26852929 TI - ECG pattern of STEMI equivalent without coronary occlusion. PMID- 26852930 TI - Electrocardiographic estimation of successful ablation site in patients with manifest inferior paraseptal accessory pathway. AB - Inferior paraseptal accessory pathways (APs) have a wide distribution and prediction of AP location before radiofrequency ablation is very important in such pathways. We aimed to estimate successful ablation site based on electrocardiogram in 137 patients (mean age: 25.8+/-9.0; 126 males) with single manifest inferior paraseptal AP. Right endocardial inferior paraseptal APs were discriminated from left endocardial APs with an R/S ratio <1 (p<0.001) and negative delta wave in lead V1 (p<0.001). Epicardial inferior paraseptal APs were differentiated from endocardial APs by a negative delta wave in lead II (p=0.001), positive delta waves in AVR (p<0.001) and V1 (p=0.012), R/S ratio <1 in lead II (p=0.03), and R/S ratio >=1 in V1 (p=0.04). Delta wave polarity and R/S ratio in lead V1 differentiate right endocardial inferior paraseptal APs from left endocardial APs. Delta wave polarities in leads II, AVR and V1, and R/S ratios in leads II and V1 estimate epicardial inferior paraseptal APs. PMID- 26852928 TI - T cell migration, search strategies and mechanisms. AB - T cell migration is essential for T cell responses; it allows for the detection of cognate antigen at the surface of antigen-presenting cells and for interactions with other cells involved in the immune response. Although appearing random, growing evidence suggests that T cell motility patterns are strategic and governed by mechanisms that are optimized for both the activation stage of the cell and for environment-specific cues. In this Opinion article, we discuss how the combined effects of T cell-intrinsic and -extrinsic forces influence T cell motility patterns in the context of highly complex tissues that are filled with other cells involved in parallel motility. In particular, we examine how insights from 'search theory' can be used to describe T cell movement across an 'exploitation-exploration trade-off' in the context of activation versus effector function and lymph nodes versus peripheral tissues. PMID- 26852932 TI - alpha-Regioselective Asymmetric [3 + 2] Annulations of Morita-Baylis-Hillman Carbonates with Cyclic 1-Azadienes and Mechanism Elucidation. AB - An alpha-regio-, diastereo-, and enantioselective [3 + 2] annulation reaction of Morita-Baylis-Hillman carbonates of isatins and activated alkenes with a bulky electron-withdrawing 1,2-benzoisothiazole 1,1-dioxide or 1,2,3-benzoxathiazine 2,2-dioxide motif is reported, furnishing an array of spirooxindoles (>19:1 dr, up to >99% ee) catalyzed by cinchona-derived tertiary amines. Density functional theory calculation studies have been conducted to elucidate the originality of the alpha-regioselective annulations. PMID- 26852931 TI - Systematic review of the effect of intravenous lipid emulsion therapy for non local anesthetics toxicity. AB - BACKGROUND: The use of intravenous lipid emulsion (ILE) therapy for the treatment of lipophilic drug toxicity is increasing. Despite this, the evidence for its effect in non-local anesthetic toxicity remains sparse. Furthermore, many case reports describe ILE use for substances in which no clear efficacy data exists. The American Academy of Clinical Toxicology established a lipid emulsion workgroup. The aim of this group is to review the available evidence regarding the effect of ILE in non-LA drug poisoning and develop consensus-based recommendations on the use of this therapy. METHODS: A systematic review of the literature was performed to capture articles through 15 December 2014. Relevant articles were determined based upon a predefined methodology. Articles involving pre-treatment experiments, pharmacokinetic studies not involving toxicity, and studies not addressing antidotal use of ILE met pre-defined exclusion criteria. Agreement of at least two members of the subgroup was required before an article could be excluded. RESULTS: The final analysis included 203 articles: 141 for humans and 62 for animals. These include 40 animal experiments and 22 case reports involving animal toxicity. There were three human randomized control trials (RCT): one RCT examined ILE in TCA overdose, one RCT examined ILE in various overdoses, and one study examined ILE in reversal of sedation after therapeutic administration of inhaled anesthesia. One observational study examined ILE in glyphosate overdose. In addition, 137 human case reports or case series were identified. Intravenous lipid emulsion therapy was used in the management of overdose with 65 unique substances. CONCLUSIONS: Despite the use of ILE for multiple substances in the treatment of patients with poisoning and overdose, the effect of ILE in various non-local anesthetic poisonings is heterogenous, and the quality of evidence remains low to very low. PMID- 26852933 TI - Non-systemic Intestine-Targeted Drugs. PMID- 26852934 TI - Measurement, Interpretation and Use of Free Ligand Solution Conformations in Drug Discovery. PMID- 26852936 TI - The Evolving Role of the Medicinal Chemist. PMID- 26852935 TI - Recent Advances in the Discovery of Deubiquitinating Enzyme Inhibitors. PMID- 26852937 TI - Preface. PMID- 26852938 TI - Altruistic Metadynamics: Multisystem Biased Simulation. AB - We present a new simple extension of multiple walker metadynamics which makes it possible to simulate simultaneously multiple different molecular systems and to predict their free energy surfaces, named Altruistic metadynamics. Similarly to basic metadynamics, it uses a bias potential in the form of hills summed over the simulation. Each system adds a big hill to its "own" bias potential and smaller hills to bias potentials of other systems, hence, each system enhances sampling of other systems. This makes it possible to achieve either faster reaching of the stationary point or higher accuracy of the calculated free energy surfaces. This should be efficient in modeling of series of chemically similar systems, for example, in computational drug screening by metadynamics. The method was tested on model energy surfaces, alanine dipeptide modeled in different force fields and monosaccharides of D-hexopyranose series. PMID- 26852939 TI - Cell surface syndecan-1 contributes to binding and function of macrophage migration inhibitory factor (MIF) on epithelial tumor cells. AB - Surface expressed proteoglycans mediate the binding of cytokines and chemokines to the cell surface and promote migration of various tumor cell types including epithelial tumor cells. We here demonstrate that binding of the chemokine-like inflammatory cytokine macrophage migration inhibitory factor (MIF) to epithelial lung and breast tumor cell lines A549 and MDA-MB231 is sensitive to enzymatic digestion of heparan sulphate chains and competitive inhibition with heparin. Moreover, MIF interaction with heparin was confirmed by chromatography and a structural comparison indicated a possible heparin binding site. These results suggested that proteoglycans carrying heparan sulphate chains are involved in MIF binding. Using shRNA-mediated gene silencing, we identified syndecan-1 as the predominant proteoglycan required for the interaction with MIF. MIF binding was decreased by induction of proteolytic shedding of syndecan-1, which could be prevented by inhibition of the metalloproteinases involved in this process. Finally, MIF induced the chemotactic migration of A549 cells, wound closure and invasion into matrigel without affecting cell proliferation. These MIF-induced responses were abrogated by heparin or by silencing of syndecan-1. Thus, our study indicates that syndecan-1 on epithelial tumor cells promotes MIF binding and MIF-mediated cell migration. This may represent a relevant mechanism through which MIF enhances tumor cell motility and metastasis. PMID- 26852940 TI - Temporal Trends in Outcomes after Out-of-Hospital Cardiac Arrests Witnessed by Emergency Medical Services in Japan: A Population-Based Study. AB - OBJECTIVE: Survival after out-of-hospital cardiac arrests (OHCA) witnessed by emergency medical service (EMS) personnel has been insufficiently understood. The aim of this study was to evaluate temporal trends in survival after EMS-witnessed OHCAs in Japan. METHODS: A nationwide, population-based, observational cohort study of consecutive adult OHCA patients with emergency responder resuscitation attempts from January 2005 to December 2012 in Japan. We assessed the trends in annual incidence, characteristics, and outcomes of OHCA patients witnessed by EMS personnel. Multiple logistic regression analysis was used to assess factors that were potentially associated with neurologically favorable outcome defined as cerebral performance category scale 1or 2. RESULTS: During the study period, a total of 66,760 EMS-witnessed OHCAs were documented. The annual incidence rates per 100,000 persons of EMS-witnessed OHCA patients increased from 4.6 (n = 7219) in 2005 to 4.9 (n = 9256) in 2012 (p for trend = 0.035). The proportion of one month survival with neurologically favorable outcome improved from 5.9% in 2005 to 8.6% in 2012 (p for trend < 0.001), and the proportion increased from 22.1% in 2005 to 30.2% in 2012 in cases with shockable rhythm (p for trend < 0.001). In a multivariate analysis, adults, male gender, shockable rhythm, presumed cardiac origin, and year were associated with a better neurological outcome. CONCLUSIONS: In this population, the proportion of one-month survival with neurologically favorable outcome among OHCA patients witnessed by EMS personnel significantly improved during the study period. PMID- 26852941 TI - Two-Dimensional Speckle-Tracking during Dobutamine Stress Echocardiography in the Detection of Myocardial Ischemia in Patients with Suspected Coronary Artery Disease. AB - BACKGROUND: Two-dimensional speckle-tracking applied to dobutamine stress echocardiography (DSE) may aid in the detection of coronary artery disease (CAD). The aim of this study was to determine the value of strain, strain rate, and postsystolic strain index (PSI) measured by speckle-tracking during DSE in the evaluation of the presence, extent, and severity of myocardial ischemia. METHODS: Fifty patients 63 +/- 7 years of age with intermediate probability of CAD were prospectively recruited. All patients underwent DSE, quantitative positron emission tomographic perfusion imaging, and invasive angiography. Regional peak systolic longitudinal strain, strain rate, and PSI were measured at rest, at a dobutamine dose of 20 MUg/kg/min, at peak stress, and at early recovery (1 min after stress). Obstructive CAD was defined as >75% stenosis or 40% to 75% stenosis combined with either fractional flow reserve < 0.80 or abnormal findings on myocardial perfusion positron emission tomography. RESULTS: Obstructive CAD was detected in 22 patients and in 36 of 150 coronary arteries. Strain analyses showed the highest reproducibility at rest, at a dobutamine dose of 20 MUg/kg/min, and at early recovery. Increased PSI and reduced strain during early recovery were the strongest predictors of obstructive CAD and were associated with the extent, localization, and depth of myocardial ischemia by positron emission tomography. On vessel-based analysis, strain, PSI, and visual analysis of wall motion provided comparable diagnostic accuracy, whereas the combination of strain or PSI with visual analysis provided incremental value over visual analysis alone. CONCLUSIONS: Assessment of systolic or postsystolic strain by speckle-tracking echocardiography during early recovery after DSE can help in the detection of hemodynamically significant coronary stenosis compared with visual wall motion analysis alone. PMID- 26852942 TI - Dnd Is a Critical Specifier of Primordial Germ Cells in the Medaka Fish. AB - Primordial germ cell (PGC) specification occurs early in development. PGC specifiers have been identified in Drosophila, mouse, and human but remained elusive in most animals. Here we identify the RNA-binding protein Dnd as a critical PGC specifier in the medaka fish (Oryzias latipes). Dnd depletion specifically abolished PGCs, and its overexpression boosted PGCs. We established a single-cell culture procedure enabling lineage tracing in vitro. We show that individual blastomeres from cleavage embryos at the 32- and 64-cell stages are capable of PGC production in culture. Importantly, Dnd overexpression increases PGCs via increasing PGC precursors. Strikingly, dnd RNA forms prominent particles that segregate asymmetrically. Dnd concentrates in germ plasm and stabilizes germ plasm RNA. Therefore, Dnd is a critical specifier of fish PGCs and utilizes particle partition as a previously unidentified mechanism for asymmetric segregation. These findings offer insights into PGC specification and manipulation in medaka as a lower vertebrate model. PMID- 26852944 TI - Intravascular US-Guided Portal Vein Access: Improved Procedural Metrics during TIPS Creation. AB - PURPOSE: To evaluate transjugular intrahepatic portosystemic shunt (TIPS) outcomes and procedure metrics with the use of three different image guidance techniques for portal vein (PV) access during TIPS creation. MATERIALS AND METHODS: A retrospective review of consecutive patients who underwent TIPS procedures for a range of indications during a 28-month study period identified a population of 68 patients. This was stratified by PV access techniques: fluoroscopic guidance with or without portography (n = 26), PV marker wire guidance (n = 18), or intravascular ultrasound (US) guidance (n = 24). Procedural outcomes and procedural metrics, including radiation exposure, contrast agent volume used, procedure duration, and PV access time, were analyzed. RESULTS: No differences in demographic or procedural characteristics were found among the three groups. Technical success, technical success of the primary planned approach, hemodynamic success, portosystemic gradient, and procedure-related complications were not significantly different among groups. Fluoroscopy time (P = .003), air kerma (P = .01), contrast agent volume (P = .003), and total procedural time (P = .02) were reduced with intravascular US guidance compared with fluoroscopic guidance. Fluoroscopy time (P = .01) and contrast agent volume (P = .02) were reduced with intravascular US guidance compared with marker wire guidance. CONCLUSIONS: Intravascular US guidance of PV access during TIPS creation not only facilitates successful TIPS creation in patients with challenging anatomy, as suggested by previous investigations, but also reduces important procedure metrics including radiation exposure, contrast agent volume, and overall procedure duration compared with fluoroscopically guided TIPS creation. PMID- 26852943 TI - Oral Triphenylmethane Food Dye Analog, Brilliant Blue G, Prevents Neuronal Loss in APPSwDI/NOS2-/- Mouse Model. AB - Reducing amyloid-beta (Abeta) accumulation is a promising strategy for developing Alzheimer's Disease (AD) therapeutics. We recently reported that a triphenylmethane food dye analog, Brilliant Blue G (BBG), is a dose-dependent modulator of in vitro amyloid-beta aggregation and cytotoxicity in cell-based assays. Following up on this recent work, we sought to further evaluate this novel modulator in a therapeutically-relevant AD transgenic mouse model. BBG was orally administered to APPSwDI/NOS2-/- mice for three months in order to assess its biocompatibility, its permeability across the blood-brain barrier, and its efficacy at rescuing AD pathology. The results showed that BBG was well tolerated, caused no significant weight change/unusual behavior, and was able to significantly cross the AD blood-brain barrier in APPSwDI/NOS2-/- mice. Immunohistochemical and electron microscopic analysis of the brain sections revealed that BBG was able to significantly prevent neuronal loss and reduce intracellular APP/Abeta in hippocampal neurons. This is the first report of 1) the effect of Brilliant Blue G on neuronal loss in a transgenic animal model of AD, 2) oral administration of BBG to affect a protein conformation/aggregation disease, and 3) electron microscopic ultrastructural analysis of AD pathology in APPSwDI/NOS2-/- mice. PMID- 26852945 TI - Evaluation of the effect of oral omeprazole on canine cerebrospinal fluid production: A pilot study. AB - Administration of omeprazole by ventriculo-cisternal perfusion or intravenously has been shown to decrease cerebrospinal fluid (CSF) production in dogs and rabbits. Oral omeprazole has consequently been recommended to reduce CSF production in dogs with conditions in which clinical signs may be attributable to an accumulation of CSF in the central nervous system (e.g. hydrocephalus, syringomyelia). The albumin quotient (QAlb), the ratio between CSF and serum albumin concentration, has been proposed as a reliable means to evaluate CSF production; decreasing CSF production should cause an increase in QAlb. The aims of this study were to assess the effect of oral administration of omeprazole on QAlb in dogs and to compare two methods to assess CSF albumin concentration. Fifteen healthy Beagle dogs received omeprazole (1.2 mg/kg/day) orally for 14 days; CSF and blood were obtained before and after treatment. CSF albumin concentrations were evaluated by nephelometry and high-resolution protein electrophoresis. Regardless of the method used for measuring albumin, QAlb did not change significantly following oral omeprazole administration, suggesting that CSF production in healthy dogs may not be affected by chronic oral therapy with omeprazole. PMID- 26852946 TI - Marginal dietary zinc concentration affects claw conformation measurements but not histological claw characteristics in weaned pigs. AB - The aim of the present study was to explore whether marginal dietary zinc (Zn) concentrations affect claw quality measurements in weaned pigs. Twenty-four weaned pigs were randomly assigned to two dietary treatment groups: (1) 42 mg Zn/kg diet from ingredients only (unsupplemented, marginal dietary Zn concentration below Zn requirements of 80 mg Zn/kg feed); and (2) 106 mg Zn/kg diet, where Zn was added as ZnO (common commercial dietary Zn concentration). Claw conformation characteristics were measured at the start (day 0, 4 weeks of age) and at the end (day 36) of the study, and the histological claw characteristics of horn wall and heel horn were examined on samples collected at 9 weeks of age. Non-supplemented pigs had narrower claw widths (P= 0.028) and lower toe heights (P= 0.010) at 9 weeks. The length of the dorsal border tended to be lower for the non-supplemented piglets (P= 0.092). Claw volume and claw horn size were lower (P= 0.003 and P < 0.001, respectively) for the non supplemented pigs at 9 weeks of age. Horn growth and wear were lower for the non supplemented pigs (P= 0.044 and P < 0.001, respectively), but net horn growth (horn growth minus wear) was not different (P= 0.406). No changes in the histological claw characteristics were observed. Differences in claw quality measurements were found between lateral and medial claw digits and between fore and hind claws. It was concluded that marginal dietary Zn concentration affected various claw quality measurements. Marginal dietary Zn concentrations may not be sufficient to maintain claw quality in pigs. PMID- 26852947 TI - [Living the aging in Senegal Perceptions/representations and coping strategies of persons of age three: results of investigations retrospective]. AB - In Senegal, due to the young age of the population (60%) the concerns of the old tend to be put in the background. And yet, problems related to old age are a reality. These problems come up not in terms of demography (the old represent only 4.7% of the population), but in terms of the breaking-up of the social fabric, urbanization and the dismantling of the solidarity and poverty networks. This work is based on a collection of qualitative data from three studies conducted between 2008 and 2011 with the elderly to assess their real- life experiences, their perception of aging, their challenges and coping strategies. The results showed a transformation in the role and status of the old; this transformation being caused by social and society-related mutations. As a result, the inter-generation solidarity links have much loosened in the urban areas making the old people more vulnerable (in economic, social, health terms), especially those in charge of a family. The situation has been made worse by the unemployment affecting their offspring. In addition, the old people, who are often suffering from chronic diseases, find it hard to take charge of their medical expenses, despite the institution of the National Sesame Health Plan for the old or free health care policy. This has made them even more vulnerable. Yet before this precarious situation, the elderly develop strategies to cope with difficulties. Some recommendations have been made with a view to improving their lives and socioeconomic condition. PMID- 26852948 TI - DHEA administration modulates stress-induced analgesia in rats. AB - An important aspect of adaptive stress response is the pain response suppression that occurs during or following stress exposure, which is often referred to as acute stress-induced analgesia. Dehydroepiandrosterone (DHEA) participates in the modulation of adaptive stress response, changing the HPA axis activity. The effect of DHEA on the HPA axis activity is dependent on the state and uses the same systems that participate in the regulation of acute stress-induced analgesia. The impact of DHEA on nociception has been studied; however, the effect of DHEA on stress-induced analgesia is not known. Thus, the aim of the present study was to evaluate the effect of DHEA on stress-induced analgesia and determine the best time for hormone administration in relation to exposure to stressor stimulus. The animals were stressed by restraint for 1h in a single exposure and received treatment with DHEA by a single injection before the stress or a single injection after the stress. Nociception was assessed with a tail flick apparatus. Serum corticosterone levels were measured. DHEA administered before exposure to stress prolonged the acute stress-induced analgesia. This effect was not observed when the DHEA was administered after the stress. DHEA treatment in non-stressed rats did not alter the nociceptive threshold, suggesting that the DHEA effect on nociception is state-dependent. The injection of DHEA had the same effect as exposure to acute stress, with both increasing the levels of corticosterone. In conclusion, acute treatment with DHEA mimics the response to acute stress indexed by an increase in activity of the HPA axis. The treatment with DHEA before stress exposure may facilitate adaptive stress response, prolonging acute stress-induced analgesia, which may be a therapeutic strategy of interest to clinics. PMID- 26852950 TI - Chronic L-DOPA administration increases the firing rate but does not reverse enhanced slow frequency oscillatory activity and synchronization in substantia nigra pars reticulata neurons from 6-hydroxydopamine-lesioned rats. AB - The pathophysiology of Parkinson's disease (PD) and of L-DOPA-induced dyskinesia (LID) is associated with dysfunctional neuronal activity in several nuclei of the basal ganglia. Moreover, high levels of oscillatory activity and synchronization have also been described in both intra- and inter-basal ganglia nuclei and the cerebral cortex. However, the relevance of these alterations in the motor symptomatology related to Parkinsonism and LID is not fully understood. Recently, we have shown that subthalamic neuronal activity correlates with axial abnormal movements and that a subthalamic nucleus (STN) lesion partially reduces LID severity as well as the expression of some striatal molecular modifications. The aim of the present study was to assess, through single-unit extracellular recording techniques under urethane anaesthesia, neuronal activity of the substantia nigra pars reticulata (SNr) and its relationship with LID and STN hyperactivity together with oscillatory and synchronization between these nuclei and the cerebral cortex in 6-OHDA-lesioned and dyskinetic rats. Twenty-four hours after the last injection of L-DOPA the firing rate and the inhibitory response to an acute challenge of L-DOPA of SNr neurons from dyskinetic animals were increased with respect to those found in intact and 6-OHDA-lesioned rats. Moreover, there was a significant correlation between the mean firing rate of SNr neurons and the severity of the abnormal movements (limb and orolingual subtypes). There was also a significant correlation between the firing activity of SNr and STN neurons recorded from dyskinetic rats. In addition, low frequency band oscillatory activity and synchronization both within the SNr or STN and with the cerebral cortex were enhanced in 6-OHDA-lesioned animals and not or slightly affected by chronic treatment with L-DOPA. Altogether, these results indicate that neuronal SNr firing activity is relevant in dyskinesia and may be driven by STN hyperactivity. Conversely, low frequency oscillatory activity and synchronization seem to be more important in PD because they are not influenced by prolonged L-DOPA administration. PMID- 26852951 TI - The dynamic mechanism of presenilin-1 function: Sensitive gate dynamics and loop unplugging control protein access. AB - There is no molecular explanation for the many presenilin 1 (PSEN1) mutations causing Alzheimer's disease, but both gain of function relating to amyloid production and loss of isolated PSEN1 function have been implied. We report here the first detailed dynamic all-atom model of mature PSEN1 from molecular dynamics in an explicit membrane with particular account of the as yet unexplored loop dynamics. We find that mature PSEN1 contains multiple distinct conformational states whereas non-mature PSEN1 is a typical one-state protein. We confirm a previously suggested gating mechanism, and find that the 106-131 loop acts as a "hinge" for the TM2 and TM6 "doors". More importantly, we identify an unplugging mechanism of the Exon 9 loop associated only with mature PSEN1. Proper opening of both the "gate" and "plug" in the membrane produces channel-like morphologies and access to the catalytic aspartates. Dynamically, these features seem linked. The long-range sensitivity of this gate-plug system to subtle conformational changes can explain why so many PSEN1 mutants cause disease. Reduced access and imprecise substrate cleavage associated with impaired gate-plug dynamics is directly illustrated by the effect of maturation in our work and could explain the overall reduction in Abeta levels upon PSEN1 mutation and the increase in the Abeta 42/40 ratio. Yet, our PSEN1-only dynamics are particularly insightful in revealing PSEN1-only dynamics relating to e.g. its role as membrane channel. Thus, our identified gate-plug mechanism is relevant for designing PSEN1 modulating therapies for treatment of Alzheimer's disease within both the amyloid/gamma secretase hypothesis and within the PSEN1 loss of function paradigm. PMID- 26852949 TI - Time-dependent behavioral, neurochemical, and metabolic dysregulation in female C57BL/6 mice caused by chronic high-fat diet intake. AB - High-fat diet (HFD) induced obesity is associated not only with metabolic dysregulation, e.g., impaired glucose homeostasis and insulin sensitivity, but also with neurological dysfunction manifested with aberrant behavior and/or neurotransmitter imbalance. Most studies have examined HFD's effects predominantly in male subjects, either in the periphery or on the brain, in isolation and after a finite feeding period. In this study, we evaluated the time course of selected metabolic, behavioral, and neurochemical effects of HFD intake in parallel and at multiple time points in female (C57BL/6) mice. Peripheral effects were evaluated at three feeding intervals (short: 5-6 weeks, long: 20-22 weeks, and prolonged: 33-36 weeks). Central effects were evaluated only after long and prolonged feeding durations; we have previously reported those effects after the short (5-6 weeks) feeding duration. Ongoing HFD feeding resulted in an obese phenotype characterized by increased visceral adiposity and, after prolonged HFD intake, an increase in liver and kidney weights. Peripherally, 5 weeks of HFD intake was sufficient to impair glucose tolerance significantly, with the deleterious effects of HFD being greater with prolonged intake. Similarly, 5 weeks of HFD consumption was sufficient to impair insulin sensitivity. However, sensitivity to insulin after prolonged HFD intake was not different between control, low-fat diet (LFD) and HFD-fed mice, most likely due to age-dependent decrease in insulin sensitivity in the LFD-fed mice. HFD intake also induced bi-phasic hepatic inflammation and it increased gut permeability. Behaviorally, prolonged intake of HFD caused mice to be hypoactive and bury fewer marbles in a marble burying task; the latter was associated with significantly impaired hippocampal serotonin homeostasis. Cognitive (short-term recognition memory) function of mice was unaffected by chronic HFD feeding. Considering our prior findings of short-term (5-6 weeks) HFD-induced central (hyperactivity/anxiety and altered ventral hippocampal neurochemistry) effects and our current results, it seems that in female mice some metabolic/inflammatory dysregulations caused by HFD, such as gut permeability, appear early and persist, whereas others, such as glucose intolerance, are exaggerated with continuous HFD feeding; behaviorally, prolonged HFD consumption mainly affects locomotor activity and anxiety-like responses, likely due to the advanced obesity phenotype; neurochemically, the serotonergic system appears to be most sensitive to continued HFD feeding. PMID- 26852952 TI - Curcumin analog L3 alleviates diabetic atherosclerosis by multiple effects. AB - L3, an analog of curcumin, is a compound isolated from a traditional Chinese medicine Turmeric. In this paper, we aims to explore the efficacy of L3 on diabetic atherosclerosis and the related mechanism. The effect of L3 was studied on glucose and lipid metabolism, antioxidant status, atherosclerosis-related indexes and pathological changes of main organs in the mice model of diabetes induced by streptozotocin and high-fat diet. The results showed that L3 treatment could meliorate dyslipidemia and hyperglycemia, reduce oxidative stress, enhance the activity of antioxidases, increase the nitric oxide level in plasma and aortic arch, decrease the production of reactive oxygen species in pancreas and lectin-like oxidized low-density lipoprotein receptor-1 expression in aortic arch, and meliorate the fatty and atherosclerotic degeneration in aortic arch, thereby preventing the development of diabetes and its complications. These results suggested that L3 can alleviate the diabetic atherosclerosis by multiple effects. This study provided scientific basis for the further research and clinical application of L3. PMID- 26852953 TI - A tetramethoxychalcone from Chloranthus henryi suppresses lipopolysaccharide induced inflammatory responses in BV2 microglia. AB - Neuroinflammation underlies the pathogenesis and progression of neurodegenerative diseases. 2'-hydroxy-4,3',4',6'-tetramethoxychalcone (HTMC) is a known chalcone derivative isolated from Chloranthus henryi with anti-inflammatory activities in BV2 macrophages. However, its pharmacological effects on microglial cells have not been demonstrated. To this end, we examined the effects of HTMC on lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglial cells. HTMC concentration-dependently inhibited LPS-induced expression of inflammatory enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nitric oxide (NO) production, and the secretion of inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6. In addition, HTMC inhibited reactive oxygen species (ROS) production by reducing NADPH oxidase (Nox) 2 and Nox4 expression. In addition, HTMC interfered LPS-induced c-Jun N-terminal kinase 1/2 (JNK) phosphorylation in a time- and concentration-dependent manner. By inhibiting phosphorylation and nuclear translocation of Jun, HTMC suppressed LPS-induced activator protein-1 (AP-1) activation. Taken together, our data indicate that HTMC suppresses inflammatory responses in LPS-stimulated BV2 microglial cells by modulating JNK-AP-1 and NADPH oxidases-ROS pathways. HTMC represents a promising therapeutic agent for neurodegenerative and related aging-associated diseases. PMID- 26852954 TI - Increase of human prostate cancer cell (DU145) apoptosis by telmisartan through PPAR-delta pathway. AB - The effect of telmisartan on prostate cancer DU145 cell survival and the underlying mechanism of apoptosis involving peroxisome proliferator-activated receptor (PPAR) pathway were investigated. Cultured DU145 cells were treated pharmacologically with telmisartan and GSK0660 (a PPAR-delta antagonist); or by RNA interference with siRNA of PPAR-delta. The treatment effects on cell survival were evaluated with cell viability assay, life and dead cell staining and flow cytometry. Western blot analysis for PPAR-delta protein expression was also performed. The results showed that telmisartan (0-80 um) dose-dependently reduced DU145 cell survival. Flow cytometry demonstrated cancer cell cycle arrest with increase of sub-G1 phase. GSK0660 partially but significantly restored the telmisartan-treated cell viability. Similarly, siRNA of PPAR-delta significantly reversed the telmisartan-induced apoptosis. Western blot showed that telmisartan significantly increased DU145 cell PPAR-delta protein expression. Co-incubation with siRNA of PPAR-delta inhibited the telmisartan effect of PPAR-delta up regulation. In conclusion, telmisartan induces prostate cancer DU145 cells apoptosis through the up-regulation of PPAR-delta protein expression. Pharmacological inhibition or genetic silencing of PPAR-delta activity can both reverse the telmisartan-induced apoptotic effect. Thus the PPAR-delta pathway might be a potential target for the treatment of prostate cancer. PMID- 26852955 TI - Cannabinoid pharmacology in cancer research: A new hope for cancer patients? AB - Cannabinoids have been used for many centuries to ease pain and in the past decade, the endocannabinoid system has been implicated in a number of pathophysiological conditions, such as mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis, spinal cord injury, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity, and osteoporosis. Several studies have demonstrated that cannabinoids also have anti-cancer activity and as cannabinoids are usually well tolerated and do not produce the typical toxic effects of conventional chemotherapies, there is considerable merit in the development of cannabinoids as potential anticancer therapies. Whilst the presence of psychoactive effects of cannabinoids could prevent any progress in this field, recent studies have shown the value of the non-psychoactive components of cannabinoids in activating apoptotic pathways, inducing anti-proliferative and anti-angiogenic effects. The aforementioned effects are suggested to be through pathways such as ERK, Akt, mitogen-activated protein kinase (MAPK) pathways, phosphoinositide 3-kinase (PI3K) pathways and hypoxia inducible factor 1 (HIF1), all of which are important contributors to the hallmarks of cancer. Many important questions still remain unanswered or are poorly addressed thus necessitating further research at basic pre-clinical and clinical levels. In this review, we address these issues with a view to identifying the key challenges that future research needs to address. PMID- 26852956 TI - Baclofen differentially mediates fructose-conditioned flavor preference and quinine-conditioned flavor avoidance in rats. AB - Rats display both fructose-conditioned flavor preference (CFP) and quinine conditioned flavor avoidance (CFA). Dopamine (D1 and D2), muscarinic and nicotinic, but not NMDA or opioid receptor antagonists reduced fructose-CFP expression. Dopamine D1, dopamine D2, muscarinic or NMDA, but not opioid or nicotinic receptor antagonists reduced fructose-CFP acquisition. Dopamine D1, NMDA, nicotinic or opioid, but not dopamine D2 or muscarinic receptor antagonists enhanced quinine-CFA acquisition. Baclofen (BAC), a GABAB receptor agonist, alternately enhances or reduces feeding under specific conditions. The present study examined whether systemic BAC administration mediated fructose-CFP expression and acquisition or quinine-CFA acquisition. Fructose-CFP expression studies trained rats with one flavor (CS+) in 8% fructose and 0.2% saccharin and a second (CS-) flavor in 0.2% saccharin, followed by vehicle (VEH) and BAC (0.5-5 mg/kg) preceding 2-bottle (CS+, CS-) 0.2% saccharin choice tests. Fructose-CFP acquisition studies administered VEH or BAC (3 or 5 mg/kg) prior to CS+ and CS- training sessions followed by six 2-bottle (CS+, CS-) 0.2% saccharin choice tests. Quinine-CFA acquisition studies administered VEH or BAC (3 or 5 mg/kg) prior to CS- (8% fructose+0.2% saccharin) and CS+ (fructose+saccharin+0.030% quinine) training sessions followed by six 2-bottle (CS-, CS+) fructose+saccharin choice tests. BAC (3 mg/kg) minimally (66%) reduced fructose-CFP expression. BAC failed to alter fructose-CFP acquisition. Quinine-CFA acquisition was enhanced by the 5 mg/kg BAC dose (15-25%) relative to VEH (34-48%). These data implicate GABAB receptor signaling in acquisition of quinine avoidance with minimal or no effects upon fructose preferences. PMID- 26852957 TI - Inhibitory gene expression of the Cav3.1 T-type calcium channel to improve neuronal injury induced by lidocaine hydrochloride. AB - Cav3.1 is a low-voltage-activated (LVA) calcium channel that plays a key role in regulating intracellular calcium ion levels. In this study, we observed the effects of lidocaine hydrochloride on the pshRNA-CACNA1G-SH-SY5Y cells that silenced Cav3.1 mRNA by RNA interference, and investigated the roles of p38 MAPK in these effects. We constructed the pNC-puro-CACNA1G-SH-SY5Y cells and pshRNA CACNA1G -SH-SY5Y cells by the RNA interference. All the cells were cultured with or without 10mM lidocaine hydrochloride for 24 h. The cell morphology, cell viability, Cav3.1 and p38 protein expression, cell apoptosis rate and intracellular calcium ion concentration were detected. We found that all cells treated with 10mM lidocaine hydrochloride for 24 h showed cellular rounding, axonal regression, and cellular floating. Compared with the cells in SH-SY5Y+Lido group and NC+Lido group, those in the RNAi+Lido group showed similar changes, but of smaller magnitude. Additionally, following lidocaine hydrochloride all cells displayed increased Cav3.1 and p38 MAPK protein, apoptosis rate, and intracellular calcium ion levels; however,these changes in the RNAi+Lido group were less pronounced than in the SH-SY5Y+Lido and NC+Lido groups. The cell viability decreased following lidocaine hydrochloride treatment, but viability of the cells in the RNAi+Lido group was higher than in the SH-SY5Y+Lido and NC+Lido groups. The results showed that Cav3.1 may be involved in neuronal injury induced by lidocaine hydrochloride and that p38 MAPK phosphorylation was reduced upon Cav3.1 gene silencing. PMID- 26852958 TI - The expression of tachykinin receptors in the human lower esophageal sphincter. AB - Mammalian tachykinins are a family of neuropeptides which are potent modulators of smooth muscle function with a significant contractile effect on human smooth muscle preparations. Tachykinins act via three distinct G protein-coupled neurokinin (NK) receptors, NK1, NK2 and NK3, coded by the genes TACR1, TACR2 and TACR3 respectively. The purpose of this paper was to measure the mRNA and protein expression of these receptors and their isoforms in the clasp and sling fibers of the human lower esophageal sphincter complex and circular muscle from the adjacent distal esophagus and proximal stomach. We found differences in expression between the different receptors within these muscle types, but the rank order of the receptor expression did not differ between the different muscle types. The rank order of the mRNA expression was TACR2 (alpha isoform)>TACR2 (beta isoform)>TACR1 (short isoform)>TACR1 (long isoform)>TACR3. The rank order of the protein expression was NK2>NK1>NK3. This is the first report of the measurement of the transcript and protein expression of the tachykinin receptors and their isoforms in the muscles of the human lower esophageal sphincter complex. The results provide evidence that the tachykinin receptors could contribute to the regulation of the human lower esophageal sphincter, particularly the TACR2 alpha isoform which encodes the functional isoform of the tachykinin NK2 receptor was the most highly expressed of the tachykinin receptors in the muscles associated with the lower esophageal sphincter. PMID- 26852959 TI - Mast cells in gastrointestinal disorders. AB - Mast cells are constitutively found in the gastrointestinal (GI) tract. The three major physiological functions of GI mast cells comprise of - as far as we know - regulation of GI functions, namely epithelial and endothelial functions, crosstalk with the enteric nervous system, and contribution to the host defense against bacterial, viral and parasitic agents. A number of chronic GI diseases, including inflammatory bowel disease (Crohn's disease, ulcerative colitis), celiac disease, irritable bowel syndrome, and food allergies, are thought to be associated with mast cell hyperplasia and humoral activity. Clinical conditions characterized by a decrease in mast cell functionality are not known so far. In the present review, we summarize current evidence which show that human mast cells play a central role at the GI barrier, both in health and disease. PMID- 26852961 TI - Charcot spinal arthropathy after spinal cord injury. PMID- 26852962 TI - Bipartite atlas in a trauma patient. PMID- 26852960 TI - Poor Gait Performance and Prediction of Dementia: Results From a Meta-Analysis. AB - BACKGROUND: Poor gait performance predicts risk of developing dementia. No structured critical evaluation has been conducted to study this association yet. The aim of this meta-analysis was to systematically examine the association of poor gait performance with incidence of dementia. METHODS: An English and French Medline search was conducted in June 2015, with no limit of date, using the medical subject headings terms "Gait" OR "Gait Disorders, Neurologic" OR "Gait Apraxia" OR "Gait Ataxia" AND "Dementia" OR "Frontotemporal Dementia" OR "Dementia, Multi-Infarct" OR "Dementia, Vascular" OR "Alzheimer Disease" OR "Lewy Body Disease" OR "Frontotemporal Dementia With Motor Neuron Disease" (Supplementary Concept). Poor gait performance was defined by standardized tests of walking, and dementia was diagnosed according to international consensus criteria. Four etiologies of dementia were identified: any dementia, Alzheimer disease (AD), vascular dementia (VaD), and non-AD (ie, pooling VaD, mixed dementias, and other dementias). Fixed effects meta-analyses were performed on the estimates in order to generate summary values. RESULTS: Of the 796 identified abstracts, 12 (1.5%) were included in this systematic review and meta-analysis. Poor gait performance predicted dementia [pooled hazard ratio (HR) combined with relative risk and odds ratio = 1.53 with P < .001 for any dementia, pooled HR = 1.79 with P < .001 for VaD, HR = 1.89 with P value < .001 for non-AD]. Findings were weaker for predicting AD (HR = 1.03 with P value = .004). CONCLUSIONS: This meta-analysis provides evidence that poor gait performance predicts dementia. This association depends on the type of dementia; poor gait performance is a stronger predictor of non-AD dementias than AD. PMID- 26852963 TI - Cervical spinal cord herniation along with epidural cyst after posterior cervical spine surgery. PMID- 26852964 TI - Intradural extramedullary non-myxopapillary ependymoma with a lumbar nerve root involvement in a Japanese man. PMID- 26852965 TI - Vertebral artery injury associated with cervical spine fracture dislocation. PMID- 26852966 TI - Re: Five-Year Analysis of a Multi-Institutional Prospective Clinical Trial of Delayed Intervention and Surveillance for Small Renal Masses: The DISSRM Registry. PMID- 26852967 TI - Re: Trifecta and Optimal Perioperative Outcomes of Robotic and Laparoscopic Partial Nephrectomy in Surgical Treatment of Small Renal Masses: A Multi Institutional Study. PMID- 26852968 TI - Re: A Nonrandomized Prospective Comparison of Robotic-Assisted Partial Nephrectomy in the Elderly to a Younger Cohort: An Analysis of 339 Patients with Intermediate-Term Follow-up. PMID- 26852969 TI - Re: Multiparametric 3-T MRI for Differentiating Low- versus High-Grade and Category T1 versus T2 Bladder Urothelial Carcinoma. PMID- 26852970 TI - Re: Adjuvant Cisplatin-Based Combined Chemotherapy for Lymph Node (LN)-Positive Urothelial Carcinoma of the Bladder (UCB) after Radical Cystectomy (RC): A Retrospective International Study of >1500 Patients. PMID- 26852971 TI - Re: Does Preoperative Magnetic Resonance Imaging Reduce the Rate of Positive Surgical Margins at Radical Prostatectomy in a Randomised Clinical Trial? PMID- 26852972 TI - Re: National Prostate Cancer Screening Rates after the 2012 US Preventive Services Task Force Recommendation Discouraging Prostate-Specific Antigen-Based Screening. PMID- 26852973 TI - Re: Survival with Newly Diagnosed Metastatic Prostate Cancer in the "Docetaxel Era": Data from 917 Patients in the Control Arm of the STAMPEDE Trial (MRC PR08, CRUK/06/019). PMID- 26852974 TI - Re: Importance of Local Control in Early-Stage Prostate Cancer: Outcomes of Patients with Positive Post-Radiation Therapy Biopsy Results Treated in RTOG 9408. PMID- 26852975 TI - Re: Anterior Prostate Cancer: Diagnostic Performance of T2-Weighted MRI and an Apparent Diffusion Coefficient Map. PMID- 26852976 TI - Re: Trends in Management for Patients with Localized Prostate Cancer, 1990-2013. PMID- 26852977 TI - Re: Intermittent vs Continuous Androgen Deprivation Therapy for Prostate Cancer: A Systematic Review and Meta-Analysis. PMID- 26852978 TI - Re: Urinary Incontinence and Erectile Dysfunction after Robotic versus Open Radical Prostatectomy: A Prospective, Controlled, Nonrandomised Trial. PMID- 26852979 TI - Re: Early Urinary Continence Recovery after Robot-Assisted Radical Prostatectomy in Older Australian Men. PMID- 26852980 TI - Re: Management Trends in Stage I Testicular Seminoma: Impact of Race, Insurance Status, and Treatment Facility. PMID- 26852981 TI - Re: The Preventive Antibiotics in Stroke Study (PASS): A Pragmatic Randomised Open-Label Masked Endpoint Clinical Trial. PMID- 26852982 TI - Re: Impact of a Computerized Decision Support System on Compliance with Guidelines on Antibiotics Prescribed for Urinary Tract Infections in Emergency Departments: A Multicentre Prospective before-and-after Controlled Interventional Study. PMID- 26852983 TI - Re: Ketamine Cystitis: Practical Considerations in Management. PMID- 26852984 TI - Re: The Efficacy of Pregabalin for Prevention of Catheter-Related Bladder Discomfort: A Prospective, Randomized, Placebo-Controlled Double-Blind Study. PMID- 26852985 TI - Re: Multiparametric MRI Findings of Granulomatous Prostatitis after Intravesical bacillus Calmette-Guerin Therapy in a Patient Undergoing Active Surveillance. PMID- 26852986 TI - Re: Stone Composition among First-Time Symptomatic Kidney Stone Formers in the Community. PMID- 26852987 TI - Re: Can Sexual Intercourse be an Alternative Therapy for Distal Ureteral Stones? A Prospective, Randomized, Controlled Study. PMID- 26852988 TI - Re: Effect of Demographics on Excretion of Key Urinary Factors Related to Kidney Stone Risk. PMID- 26852989 TI - Re: Developing an Internationally-Applicable Service Specification for Continence Care: Systematic Review, Evidence Synthesis and Expert Consensus. PMID- 26852990 TI - Re: Associations between Supplemental or Dietary Intake of Vitamin C and Severity of Lower Urinary Tract Symptoms. PMID- 26852991 TI - Re: TRP Channels in Lower Urinary Tract Dysfunction. PMID- 26852992 TI - Re: Regenerative Treatment of Male Stress Urinary Incontinence by Periurethral Injection of Autologous Adipose-Derived Regenerative Cells: 1-Year Outcomes in 11 Patients. PMID- 26852993 TI - Re: Central Role of the BK Channel in Urinary Bladder Smooth Muscle Physiology and Pathophysiology. PMID- 26852994 TI - Re: TVT versus Laparoscopic Mesh Colposuspension: 5-Year Follow-up Results of a Randomized Clinical Trial. PMID- 26852995 TI - Re: Long-Term Cognitive and Functional Effects of Potentially Inappropriate Medications in Older Women. PMID- 26852996 TI - Re: The Role of the Bipolar PlasmaKinetic TURP over 100 g Prostate in the Elderly Patients. PMID- 26852997 TI - Re: Initial Treatment of Men with Newly Diagnosed Lower Urinary Tract Dysfunction in the Veterans Health Administration. PMID- 26852998 TI - Re: Analyzing Why Men Seek Treatment for Lower Urinary Tract Symptoms and Factors Associated with Nonimprovement. PMID- 26852999 TI - Re: Incidence of Urethral Stricture after Bipolar Transurethral Resection of the Prostate Using TURis: Results from a Randomised Trial. PMID- 26853000 TI - Re: Burden of Male Lower Urinary Tract Symptoms (LUTS) Suggestive of Benign Prostatic Hyperplasia (BPH)-Focus on the UK. PMID- 26853001 TI - Re: Proportion of Tadalafil-Treated Patients with Clinically Meaningful Improvement in Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia-Integrated Data from 1,499 Study Participants. PMID- 26853002 TI - Re: Heart Rate Variability: A Risk Factor for Female Sexual Dysfunction. PMID- 26853003 TI - Re: Sexual Problems among Older Women by Age and Race. PMID- 26853004 TI - Re: Longitudinal Evaluation of Sexual Function in a Cohort of Pre- and Postmenopausal Women. PMID- 26853005 TI - Re: Female Sexual Function before and after Bariatric Surgery: A Cross-Sectional Study and Review of Literature. PMID- 26853006 TI - Re: Screening and Monitoring in Men Prescribed Testosterone Therapy in the U.S., 2001-2010. PMID- 26853007 TI - Re: Risk of Venous Thromboembolism in Men Receiving Testosterone Therapy. PMID- 26853008 TI - Re: Critical Update of the 2010 Endocrine Society Clinical Practice Guidelines for Male Hypogonadism: A Systematic Analysis. PMID- 26853009 TI - Re: Women's Perception of Transvaginal Natural Orifice Transluminal Endoscopic Surgery (NOTES): Results of a Survey of Female Medical Staff and Literature Review. PMID- 26853010 TI - Re: American Association of Clinical Endocrinologists and American College of Endocrinology Position Statement on the Association of Testosterone and Cardiovascular Risk. PMID- 26853011 TI - Re: Examining Postoperative Outcomes after Employing a Surgical Algorithm for Management of Peyronie's Disease: A Single-Institution Retrospective Review. PMID- 26853012 TI - Re: Responsiveness of the Peyronie's Disease Questionnaire (PDQ). PMID- 26853013 TI - Re: X-Linked TEX11 Mutations, Meiotic Arrest, and Azoospermia in Infertile Men. PMID- 26853014 TI - Re: Prospective Evaluation of Postoperative Penile Rehabilitation: Penile Length/Girth Maintenance 1 Year following Coloplast Titan Inflatable Penile Prosthesis. PMID- 26853015 TI - Re: DNA Methylation Differences between In Vitro- and In Vivo-Conceived Children are Associated with ART Procedures Rather than Infertility. PMID- 26853016 TI - Re: DNA Double Strand Breaks in Human Spermatozoa can be Predictive for Assisted Reproductive Outcome. PMID- 26853017 TI - Re: Fluorescence In Situ Hybridization Detects Increased Sperm Aneuploidy in Men with Recurrent Pregnancy Loss. PMID- 26853018 TI - Re: Interferometric Phase Microscopy for Label-Free Morphological Evaluation of Sperm Cells. PMID- 26853019 TI - Re: Aged Men Share the Sperm Protein PATE1 Defect with Young Asthenozoospermia Patients. PMID- 26853020 TI - Re: Concordance among Sperm Deoxyribonucleic Acid Integrity Assays and Semen Parameters. PMID- 26853021 TI - Re: Effect of Seminal Leukocytes on In Vitro Fertilization and Intracytoplasmic Sperm Injection Outcomes. PMID- 26853022 TI - Re: Fruit and Vegetable Intake and Their Pesticide Residues in Relation to Semen Quality among Men from a Fertility Clinic. PMID- 26853023 TI - Re: No Association between Body Mass Index and Sperm DNA Integrity. PMID- 26853024 TI - Re: Does Listening to Music during Office-Based Flexible Cystoscopy Decrease Anxiety in Patients: A Prospective Randomized Trial. PMID- 26853025 TI - Re: Cancer Mortality Reductions were Greatest among Countries where Cancer Care Spending Rose the Most, 1995-2007. PMID- 26853026 TI - Re: Association of Pioneer Accountable Care Organizations vs Traditional Medicare Fee for Service with Spending, Utilization, and Patient Experience. PMID- 26853027 TI - Re: Trends in Health Insurance Enrollment, 2013-15. PMID- 26853028 TI - Re: Program Directors' Criteria for Selection into Urology Residency. PMID- 26853029 TI - Re: Outcomes of Daytime Procedures Performed by Attending Surgeons after Night Work. PMID- 26853030 TI - Re: To Tell or Not: Parental Thoughts on Disclosure of Urologic Surgery to Their Child. PMID- 26853031 TI - Re: Screening for Depression and Anxiety in Childhood Neurogenic Bladder Dysfunction. PMID- 26853032 TI - Re: Multicystic Dysplastic Kidney: Is an Initial Voiding Cystourethrogram Necessary? PMID- 26853033 TI - Re: Nadir Creatinine in Posterior Urethral Valves: How High is Low Enough? PMID- 26853034 TI - Re: Medical Expulsive Therapy for Pediatric Urolithiasis: Systematic Review and Meta-Analysis. PMID- 26853035 TI - Re: Hyperoxaluria and Genitourinary Disorders in Children Ingesting Almond Milk Products. PMID- 26853036 TI - Re: PLCepsilon Knockdown Inhibits Prostate Cancer Cell Proliferation via Suppression of Notch Signalling and Nuclear Translocation of the Androgen Receptor. PMID- 26853037 TI - Re: mTORC1 Drives HIF-1alpha and VEGF-A Signalling via Multiple Mechanisms Involving 4E-BP1, S6K1 and STAT3. PMID- 26853038 TI - Re: A Floating Hydrogel System Capable of Generating CO2 Bubbles to Diminish Urinary Obstruction after Intravesical Instillation. PMID- 26853039 TI - Re: Regulation of the ITGA2 Gene by Epigenetic Mechanisms in Prostate Cancer. PMID- 26853041 TI - An R package for the integrated analysis of metabolomics and spectral data. AB - Recently, there has been a growing interest in the field of metabolomics, materialized by a remarkable growth in experimental techniques, available data and related biological applications. Indeed, techniques as nuclear magnetic resonance, gas or liquid chromatography, mass spectrometry, infrared and UV visible spectroscopies have provided extensive datasets that can help in tasks as biological and biomedical discovery, biotechnology and drug development. However, as it happens with other omics data, the analysis of metabolomics datasets provides multiple challenges, both in terms of methodologies and in the development of appropriate computational tools. Indeed, from the available software tools, none addresses the multiplicity of existing techniques and data analysis tasks. In this work, we make available a novel R package, named specmine, which provides a set of methods for metabolomics data analysis, including data loading in different formats, pre-processing, metabolite identification, univariate and multivariate data analysis, machine learning, and feature selection. Importantly, the implemented methods provide adequate support for the analysis of data from diverse experimental techniques, integrating a large set of functions from several R packages in a powerful, yet simple to use environment. The package, already available in CRAN, is accompanied by a web site where users can deposit datasets, scripts and analysis reports to be shared with the community, promoting the efficient sharing of metabolomics data analysis pipelines. PMID- 26853043 TI - Comment on "Retrospective evaluation of prognostic score performances in cirrhotic patients admitted to an intermediate care unit" by Benoit Dupont et al. [Digestive and Liver Disease 2015;47:675-81]. PMID- 26853042 TI - Reduction of the hydraulic retention time at constant high organic loading rate to reach the microbial limits of anaerobic digestion in various reactor systems. AB - The effects of hydraulic retention time (HRT) reduction at constant high organic loading rate on the activity of hydrogen-producing bacteria and methanogens were investigated in reactors digesting thin stillage. Stable isotope fingerprinting was additionally applied to assess methanogenic pathways. Based on hydA gene transcripts, Clostridiales was the most active hydrogen-producing order in continuous stirred tank reactor (CSTR), fixed-bed reactor (FBR) and anaerobic sequencing batch reactor (ASBR), but shorter HRT stimulated the activity of Spirochaetales. Further decreasing HRT diminished Spirochaetales activity in systems with biomass retention. Based on mcrA gene transcripts, Methanoculleus and Methanosarcina were the predominantly active in CSTR and ASBR, whereas Methanosaeta and Methanospirillum activity was more significant in stably performing FBR. Isotope values indicated the predominance of aceticlastic pathway in FBR. Interestingly, an increased activity of Methanosaeta was observed during shortening HRT in CSTR and ASBR despite high organic acids concentrations, what was supported by stable isotope data. PMID- 26853045 TI - Associations Between Penetration Cognitions, Genital Pain, and Sexual Well-being in Women with Provoked Vestibulodynia. AB - INTRODUCTION: Provoked vestibulodynia (PVD) is a common vulvovaginal pain condition that negatively impacts women's psychological and sexual well-being. Controlled studies have found that women with PVD report greater negative and less positive cognitions about penetration; however, associations between these types of cognitions and women's pain and sexual well-being remain unknown. Further, researchers have yet to examine how interpersonal variables such as sexual communication may impact the association between women's penetration cognitions and PVD outcomes. AIM: We examined associations between vaginal penetration cognitions and sexual satisfaction, sexual function, and pain in women with PVD, as well as the moderating role of sexual communication. METHODS: Seventy-seven women (M age = 28.32, SD = 6.19) diagnosed with PVD completed the catastrophic and pain cognitions and positive cognitions subscales of the Vaginal Penetration Cognition Questionnaire, as well as the Dyadic Sexual Communication Scale. Participants also completed measures of sexual satisfaction, sexual function, and pain. MAIN OUTCOME MEASURES: Dependent measures were the (i) Global Measure of Sexual Satisfaction Scale; (ii) Female Sexual Function Index; and (iii) Present Pain Intensity scale of the McGill Pain Questionnaire, with reference to pain during vaginal intercourse. RESULTS: Women's lower catastrophic and pain cognitions, higher positive cognitions, and higher sexual communication were each uniquely associated with higher sexual satisfaction and sexual function. Lower catastrophic and pain cognitions also were associated with women's lower pain. For women who reported higher sexual communication, as positive cognitions increased, there was a significantly greater decrease in pain intensity during intercourse compared to women who reported lower levels of sexual communication. CONCLUSION: Findings may inform cognitive-behavioral interventions aimed at improving the pain and sexual well-being of women with PVD. Targeting the couple's sexual communication and women's penetration cognitions may improve women's sexual adjustment and reduce pain. PMID- 26853044 TI - Beyond Anal Sex: Sexual Practices of Men Who have Sex with Men and Associations with HIV and Other Sexually Transmitted Infections. AB - INTRODUCTION: Unprotected anal intercourse is often used as a single indicator of risky behavior in men who have sex with men (MSM), yet MSM engage in a variety of behaviors that have unknown associations with sexually transmitted infection (STI) and HIV. AIM: To assess the prevalence of a wide range of sexual behaviors and their associations with prevalent STI and HIV. METHODS: We used a standardized, self-administered survey to collect behavioral data for this cross sectional study of 235 MSM seeking care in a public clinic for sexually transmitted diseases. MEAN OUTCOME MEASURES: Using modified Poisson regression, we generated unadjusted and adjusted prevalence ratios (PRs) to characterize associations between recent participation in each behavior and prevalent STI and HIV. RESULTS: Participants' median age was 26 years. One third (35%) were positive for STI. STI prevalence was significantly associated with using sex slings (adjusted PR [aPR] = 2.35), felching (aPR = 2.22), group sex (aPR = 1.86), fisting (aPR = 1.78), anonymous sex (aPR = 1.51), and sex toys (aPR = 1.46). HIV prevalence was 17% and was significantly associated with fisting (aPR = 4.75), felching (aPR = 4.22), enemas (aPR = 3.65), and group sex (aPR = 1.92). CONCLUSION: Multiple behaviors were significantly associated with prevalent STI and HIV in adjusted analyses. To provide a more comprehensive understanding of sexual risk in MSM, prospective studies are needed to examine whether these behaviors are causally associated with HIV and STI acquisition. PMID- 26853046 TI - Nonalcoholic Fatty Liver Disease is Associated with Erectile Dysfunction: A Prospective Pilot Study. AB - INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Although the link between MetS and erectile dysfunction (ED) is well known, clinical studies investigating the association between NAFLD and ED are scant. AIM: To evaluate the relationship between NAFLD and ED. METHODS: Male patients with biopsy-proven NAFLD were prospectively asked to fill the five-item International Index of Erectile Function (IIEF-5) questionnaire. Their clinical and histologic variables were compared with the IEFF scores. MAIN OUTCOME MEASURES: IIEF scores; proportions of NAFLD patients who demonstrated ED and/or MetS; association between the severity of histological hepatic damage and ED. RESULTS: Forty male patients having an age range of 33 (24-57) and a mean age of 40.13 +/- 10.22 years with biopsy-proven NAFLD had a median IIEF-5 score of 16 (9-25) and MetS was present in 23 (57.5%). ED severity distributions as moderate, mild, and no ED were 11 (27.5%), 16 (40%), and 13 (32.5 %), respectively. Histological NAFLD score was significantly higher in patients having ED compared with patients with no ED (5.63 +/- 1.39 vs. 4.15 +/- 1.46; P = .006). MetS diagnosis was significantly more common in patients having ED, compared with those without ED [19 (70.4%) vs. 4 (30.8%), respectively, P = .018)]. When patients with and without ED were compared, gamma glutamyl transferase was significantly lower in ED, whereas components of MetS did not correlate with ED. After multivariate analysis, NAFLD score has remained the only significant outcome associated with ED [P = .03; OR (95% CI): 2.38 (1.079-5.238)]. CONCLUSION: The current clinical study demonstrates a significant association between nonalcoholic steatohepatitis and ED for the first time. Our findings suggest liver damage may play role in the pathogenesis of ED in patients with NAFLD. Future studies are needed to expand the underlying common mechanisms responsible for this novel hypothesis. PMID- 26853047 TI - Decreased Endogenous Hydrogen Sulfide Generation in Penile Tissues of Diabetic Rats with Erectile Dysfunction. AB - INTRODUCTION: Hydrogen sulfide (H2S) is an endogenous gasotransmitter. The levels of H2S-generating enzyme expression and endogenous H2S production in diabetic rats with erectile dysfunction (ED) remain unknown. The aim of this study was to investigate the expression of the H2S-generating enzymes and endogenous production of H2S in penile tissues of diabetic ED rats. METHODS: Experimental rats were randomly divided into normal control group, apomorphine (APO)-positive group and APO-negative group. Primary rat corpus cavernosum smooth muscle cells (CCSMCs) and aortic endothelial cells (AECs) were isolated and cultured in vitro under 3 different conditions: normal glucose (NG) condition, high glucose (HG) condition, and osmotic control (OC) condition. MAIN OUTCOME MEASURES: Erectile function; H2S concentrations in plasma or penile tissues; expression of H2S generating enzymes and endogenous H2S production in penile tissues, CCSMCs, and AECs. RESULTS: Erectile function was significantly decreasedin the APO-negative group. In addition to significantly decreased expression of cysteine aminotransferase (CAT), d-amino acid oxidase (DAO), and 3-mercaptopyruvate sulfurtransferase (3-MST), the H2S concentrations in plasma and penile tissues and endogenous H2S production were significantly decreased in the APO-negative group. Endogenous H2S production by cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) decreased to the same levels in the APO-negative and APO-positive groups as that in the normal control group. However, CBS and CSE expression remained unchanged in the 3 groups. Under HG conditions, H2S generating enzyme expression in AECs did not change, while CAT, DAO, and 3-MST expression in CCSMCs was significantly decreased. In both cell types, H2S production by these enzymes was decreased in the HG group. CONCLUSION: Endogenous H2S production was significantly decreased in the diabetic ED rats' penile tissues due to downregulated expression of the CAT/3-MST and DAO/3-MST pathways and low activities of CBS and CSE. PMID- 26853048 TI - Health-Related Quality of Life, Psychological Distress, and Sexual Changes Following Prostate Cancer: A Comparison of Gay and Bisexual Men with Heterosexual Men. AB - INTRODUCTION: Decrements in health-related quality of life (HRQOL) and sexual difficulties are a recognized consequence of prostate cancer (PCa) treatment. However little is known about the experience of gay and bisexual (GB) men. AIM: HRQOL and psychosexual predictors of HRQOL were examined in GB and heterosexual men with PCa to inform targeted health information and support. METHOD: One hundred twenty-four GB and 225 heterosexual men with PCa completed a range of validated psychosexual instruments. MAIN OUTCOME MEASURE: Functional Assessment of Cancer Therapy-Prostate (FACT-P) was used to measure HRQOL, with validated psychosexual measures, and demographic and treatment variables used as predictors. RESULTS: GB men were significantly younger (64.25 years) than heterosexual men (71.54 years), less likely to be in an ongoing relationship, and more likely to have casual sexual partners. Compared with age-matched population norms, participants in both groups reported significantly lower sexual functioning and HRQOL, increased psychological distress, disruptions to dyadic sexual communication, and lower masculine self-esteem, sexual confidence, and sexual intimacy. In comparison with heterosexual men, GB men reported significantly lower HRQOL (P = .046), masculine self-esteem (P < .001), and satisfaction with treatment (P = .013); higher psychological distress (P = .005), cancer related distress (P < .001) and ejaculatory concern (P < .001); and higher sexual functioning (P < .001) and sexual confidence (P = .001). In regression analysis, psychological distress, cancer-related distress, masculine self-esteem, and satisfaction with treatment were predictors of HRQOL for GB men (R2Adj = .804); psychological distress and sexual confidence were predictors for heterosexual men (R2Adj = .690). CONCLUSION: These findings confirm differences between GB and heterosexual men in the impact of PCa on HRQOL across a range of domains, suggesting there is a need for GB targeted PCa information and support, to address the concerns of this "hidden population" in PCa care. PMID- 26853049 TI - Overlapping genes: A significant genomic correlate of prokaryotic growth rates. AB - Elucidating the genomic features influencing prokaryotic growth rates has always been a study of interest. Previously, it was observed that overlapping genes (OGs) play a crucial role in the prokaryotic genome size reduction. This study is focused to explore whether OGs act as a potential correlate of prokaryotic growth rates. For this purpose, we compiled a dataset of 25 archaeal and 117 eubacterial genomes and analyzed the inter-correlation between the proportion of overlapping regions in these genomes with their growth rates. Here, we observed that the proportion of overlapping region holds a significant negative correlation with generation time in archaeal domain, whereas no correlation was observed in the eubacterial domain. However, after masking the effect of tRNA, rRNA multiplicity and environmental diversity, OGs show an independent effect over growth rates in the eubacterial domain as well as in the archaeal domain. Moreover, the influence of OGs on prokaryotic growth rates provides different delineations in archaeal and eubacterial domains. In archaea, both long overlap frequency (LOF) and short overlap frequency (SOF) influence the growth rates by increasing the degree of operonization. On the contrary, in the case of bacteria, neither SOF nor LOF plays any significant role in achieving faster growth rates. PMID- 26853050 TI - Wearable ultrasonic guiding device with white cane for the visually impaired: A preliminary verisimilitude experiment. AB - Several assistive technologies are available to help visually impaired individuals avoid obstructions while walking. Unfortunately, white canes and medical walkers are unable to detect obstacles on the road or react to encumbrances located above the waist. In this study, I adopted the cyber-physical system approach in the development of a cap-connected device to compensate for gaps in detection associated with conventional aids for the visually impaired. I developed a verisimilar, experimental route involving the participation of seven individuals with visual impairment, including straight sections, left turns, right turns, curves, and suspended objects. My aim was to facilitate the collection of information required for the practical use of the device. My findings demonstrate the feasibility of the proposed guiding device in alerting walkers to the presence of some kinds of obstacles from the small number of subjects. That is, it shows promise for future work and research with the proposed device. My findings provide a valuable reference for the further improvement of these devices as well as the establishment of experiments involving the visually impaired. PMID- 26853051 TI - A Simple Approach for an Eggshell-Based 3D-Printed Osteoinductive Multiphasic Calcium Phosphate Scaffold. AB - Natural origin bioceramics are widely used for bone grafts. In the present study, an eggshell-derived bioceramic scaffold is fabricated by 3D printing as a potential bone-graft analogue. The eggshell, a biological waste material, was mixed with a specific ratio of phosphoric acid and chitosan to form a precursor toward the fabrication of an osteoinductive multiphasic calcium phosphate scaffold via a coagulation-assisted extrusion and sintering for a multiscalar hierarchical porous structure with improved mechanical properties. Physicochemical characterization of the formed scaffolds was carried out for phase analysis, surface morphology, and mechanical properties. A similar scaffold was prepared using a chemically synthesized calcium phosphate powder that was compared with the natural origin one. The higher surface area associated with the interconnected porosity along with multiple phases of the natural origin scaffold facilitated higher cell adhesion and proliferation compared to the chemically synthesized one. Further, the natural origin scaffold displayed relatively higher cell differentiation activity, as is evident by protein and gene expression studies. On subcutaneous implantation for 30 days, promising vascular tissue in growth was observed, circumventing a major foreign body response. Collagen-rich vascular extracellular matrix deposition and osteocalcin secretion indicated bonelike tissue formation. Finally, the eggshell-derived multiphasic calcium phosphate scaffold displayed improvement in the mechanical properties with higher porosity and osteoinductivity compared to the chemically derived apatite and unveiled a new paradigm for utilization of biological wastes in bone-graft application. PMID- 26853052 TI - Response to "Chemical injuries caused by the hydrofluoric acid leak". PMID- 26853054 TI - Hierarchical Cu pillar electrodes for electrochemical CO2 reduction to formic acid with low overpotential. AB - To achieve high performance of electrochemical CO2 reduction, a series of Cu pillar electrodes (Cu-2.5 h, Cu-5 h) were fabricated by using an electrodeposition method, and then their catalytic activities and reaction mechanisms were investigated. The series of Cu pillar electrodes exhibited improved electrocatalytic activities toward CO2 reduction to formic acid (HCOOH) as Cu pillars on electrodes developed. The Cu-5 h electrode performed well with a 28% Faradaic efficiency for formic acid at -0.5 V (vs. RHE). X-ray diffraction (XRD) analysis indicated that the enhanced catalytic activities were primarily attributable to the increased (111) facet, which is energetically favourable for the production of HCOOH. Also, ultraviolet photoelectron spectroscopy (UPS) and in situ electrochemical impedance spectroscopy (EIS) results suggested that the series of Cu pillar structure electrodes improved the electron transfer to adsorbed CO2 due to the decreased work function of the Cu pillar structure. PMID- 26853055 TI - Characterization of a Drinking Water Distribution Pipeline Terminally Colonized by Naegleria fowleri. AB - Free-living amoebae, such as Naegleria fowleri, Acanthamoeba spp., and Vermamoeba spp., have been identified as organisms of concern due to their role as hosts for pathogenic bacteria and as agents of human disease. In particular, N. fowleri is known to cause the disease primary amoebic meningoencephalitis (PAM) and can be found in drinking water systems in many countries. Understanding the temporal dynamics in relation to environmental and biological factors is vital for developing management tools for mitigating the risks of PAM. Characterizing drinking water systems in Western Australia with a combination of physical, chemical and biological measurements over the course of a year showed a close association of N. fowleri with free chlorine and distance from treatment over the course of a year. This information can be used to help design optimal management strategies for the control of N. fowleri in drinking-water-distribution systems. PMID- 26853056 TI - Correction: Microwave gallium-68 radiochemistry for kinetically stable bis(thiosemicarbazone) complexes: structural investigations and cellular uptake under hypoxia. PMID- 26853057 TI - Orientation-dependent nanostructure arrays based on anisotropic silicon wet etching for repeatable surface-enhanced Raman scattering. AB - Repeatable fabrication of sensitive plasmonic substrates through a simple procedure has become a major challenge for SERS-based sensing and imaging. Herein, a new class of high-performance SERS substrates, including pyramid, ridged-hexagon, and quasi-triangle nanostructures, is successfully fabricated based on the nanosphere lithography technique and anisotropic wet etching. Using the wafer-scale Cr-hole array as the etching mask, cavity-templates of various configurations are fabricated by the orientation-dependent wet etching technique, from where the nanostructure arrays are finally peeled-off. The anisotropic wet etching on (100), (110), and (111) silicon wafers has been systematically studied at the nanoscale revealing the formation mechanism of these cavity-templates. The peeled-off nanostructure arrays provide high-density tips and/or gaps (about 2.5 * 10(7) mm(-2)) and thus facilitate the generation of "hot spots". The distribution of the electromagnetic field is visualized by the finite difference time domain calculation. And the calculation results are validated by SERS characterization. The SERS enhancement factors of these substrates are in the order of 10(6)-10(7), with the maximum enhancement factor of 1.32 * 10(7) yielded by the ridged-hexagon arrays. The proposed nanostructure arrays present excellent homogeneity and reproducibility (with the largest relative standard deviation of 16.43%) for the reason that the SERS-active substrates are peeled-off from an identical template. The cost-effective fabrication, high sensitivity, good homogeneity and well-performed reproducibility demonstrate that these orientation dependent NSs are good candidates for SERS-based in vitro and in situ detection and biosensing. PMID- 26853059 TI - Topology sorting and characterization of folded polymers using nano-pores. AB - Here we report on the translocation of folded polymers through nano-pores using molecular dynamic simulations. Two cases are studied: one in which a folded molecule unfolds upon passage and one in which the folding remains intact as the molecule passes through the nano-pore. The topology of a folded polymer chain is defined as the arrangement of the intramolecular contacts, known as circuit topology. In the case where intramolecular contacts remain intact, we show that the dynamics of passage through a nano-pore varies for molecules with differing topologies: a phenomenon that can be exploited to enrich certain topologies in mixtures. We find that the nano-pore allows reading of the topology for short chains. Moreover, when the passage is coupled with unfolding, the nano-pore enables discrimination between pure states, i.e., states in which the majority of contacts are arranged identically. In this case, as we show here, it is also possible to read the positions of the contact sites along a chain. Our results demonstrate the applicability of nano-pore technology to characterize and sort molecules based on their topology. PMID- 26853058 TI - Evaluation of genotoxic variations in plant model systems in a case of metal stressors. AB - This study was designed to assess the effects of long term, high metal exposition (cadmium, lead, copper, nickel and zinc) on DNA damage in four plant model systems [Taraxacum officinale (Asteraceae), Matricaria recutita L. (Asteraceae), Robinia pseudoacacia L. (Fabaceae), and Urtica dioica (Urticaceae)]. DNA stability was investigated by a Random Amplified Polymorphic DNA (RAPD) technique. Agarose-gel electrophoresis revealed total of 37 bands with different molecular weights ranging from 1250 to 5000 bp. It generated distinctive polymorphism value of 72.97% (27 bands) total in four plant species investigated. The dendrogram constructed using NTSYSpc programme showed that there is grouping in separate clusters of the same plant model collected from two different areas (metal-exposed and control samples). The study concluded that the long term metal exposing periods had genotoxic stress on macromolecules of plant model systems investigated and biomarkers used should be augmented for reliable estimates of genotoxicity after exposure of plants to metal stressors. PMID- 26853060 TI - Hexavalent chromium removal from aqueous solutions by a novel powder prepared from Colocasia esculenta leaves. AB - In this study, batch removal of hexavalent chromium from aqueous solutions by powdered Colocasia esculenta leaves was investigated. Batch experiments were conducted to study the effects of adsorption of Cr(VI) at different pH values, initial concentrations, agitation speeds, temperatures, and contact times. The biosorbent was characterized by scanning electron microscopy, energy-dispersive X ray spectroscopy, and Fourier transform infrared spectrometer analysis. The biosorptive capacity of the adsorbent was dependent on the pH of the chromium solution in which maximum removal was observed at pH 2. The adsorption equilibrium data were evaluated for various adsorption isotherm models, kinetic models, and thermodynamics. The equilibrium data fitted well with Freundlich and Halsey models. The adsorption capacity calculated was 47.62 mg/g at pH 2. The adsorption kinetic data were best described by pseudo-second-order kinetic model. Thus, Colocasia esculenta leaves can be considered as one of the efficient and cheap biosorbents for hexavalent chromium removal from aqueous solutions. PMID- 26853062 TI - This Issue: Something for Almost Everybody. PMID- 26853061 TI - Ethnic variation in cancer patients' ratings of information provision, communication and overall care. AB - OBJECTIVE: Ethnic inequalities in cancer patient experience exist but variation within broad ethnic categories is under-explored. This study aimed to describe variation by ethnic sub-category in experiences of information provision and communication (key domains of patient experience) using National Cancer Patient Experience Survey (NCPES) data. DESIGN: The NCPES 2012-2013 contained responses from 68,737 cancer patients treated at 155 NHS Trusts in England. Multivariate logistic regression was used to investigate associations between ethnicity and patients' ratings of overall care, information provision and communication. RESULTS: Variation by and within broad ethnic categories was evident. Non-White patients (particularly Asian patients (ORadj:0.78; 95%CI:0.67-0.90, p=0.001)) were less likely than White patients to receive an understandable explanation of treatment side effects. Among Asian patients, those of Bangladeshi ethnicity were least likely to receive an understandable explanation. CONCLUSIONS: Effective communication and information provision are important to ensure patients are well informed, receive the best possible care and have a positive patient experience. However, ethnic inequalities exist in cancer patients' experiences of information provision and communication with variation evident both between and within broad ethnic categories. Further work to understand the causes of this variation is required to address ethnic inequalities at practice and policy level. PMID- 26853063 TI - In Memoriam: Jerry B. Crittenden. PMID- 26853064 TI - Single-Case Design Research: Building the Evidence-Base in the Field of Education of Deaf and Hard of Hearing Students. AB - The field of education of deaf and hard of hearing (DHH) students has a paucity of evidence-based practices (EBPs) to guide instruction. The authors discussed how the research methodology of single-case design (SCD) can be used to build EBPs through direct and systematic replication of studies. An overview of SCD research methods is presented, including an explanation of how internal and external validity issues are addressed, and why SCD is appropriate for intervention research with DHH children. The authors then examine the SCD research in the field according to quality indicators (QIs; at the individual level and as a body of evidence) to determine the existing evidence base. Finally, future replication areas are recommended to fill the gaps in SCD research with students who are DHH in order to add to the evidence base in the field. PMID- 26853065 TI - Successful Students Who Are Deaf or Hard of Hearing and Culturally and/or Linguistically Diverse in Inclusive Settings. AB - The population of students who are deaf or hard of hearing is becoming more culturally and/or linguistically diverse. However, there is a paucity of practitioner literature and research available to professionals and families to guide decision making about daily practices with these students and their families. The study identified factors that contribute to the success of students who are deaf or hard of hearing and from culturally and/or linguistically diverse backgrounds who receive the majority of their education in inclusive settings. Students were recruited from two schools in two school districts in a western state. Students, educators, interpreters, and parents participated in individual in-depth, semi-structured interviews. Observations of the students were also done. Analysis of the data included coding the transcribed interviews and the field notes to identify common themes. Seven themes emerged and are reported. Recommendations for future research are provided. PMID- 26853066 TI - College and Career Readiness: Course Taking Of Deaf and Hard of Hearing Secondary School Students. AB - Research shows that deaf and hard of hearing (DHH) students frequently enter college and the workplace relatively unprepared for success in math, science, and reading. Based on data from the National Longitudinal Transition Study-2 (NLTS2), the present study focused on DHH students' college and career readiness by investigating their opportunities in secondary school to acquire college and career skills. DHH students earned more credits overall than hearing peers; both groups earned a similar number of credits in academic courses. However, DHH students took more vocational and nonacademic courses and fewer courses in science, social science, and foreign languages. There was evidence that DHH students' academic courses in math lacked the rigor of those taken by hearing peers, as DHH students earned more credits in basic math and fewer credits in midlevel math courses, and even fewer in advanced math courses, than hearing peers. PMID- 26853067 TI - A Discourse of "Abnormality": Exploring Discussions of People Living in Australia With Deafness or Hearing Loss. AB - Adopting a social constructionist framework, the authors conducted a synthetic discourse analysis to explore how people living in Australia with deafness construct their experience of deafness. An online forum facilitated access and communication between the lead author and 24 widely dispersed and linguistically diverse forum contributors. The authors discuss the productive and restrictive effects of the emergent discourse of deafness as abnormal and the rhetorical strategies mobilized in people's accounts: fitting in, acceptance as permission to be different, and the need to prove normality. Using these strategies was productive in that the forum respondents were enabled to reposition deafness as a positive, socially valued identity position. However, the need to manage deafness was reproduced as an individual concern, disallowing any exploration of how deafness could be reconstructed as socially valued. The article concludes with a discussion of the implications of the deafness as abnormal discourse. PMID- 26853068 TI - Increasing Self-Regulation and Classroom Participation of a Child Who Is Deafblind. AB - Self-regulation has been identified as essential to school success. However, for a variety of reasons, its development may be compromised in children and youth who are deafblind. A single-case multiple-baseline study of a child who was deafblind examined the effects of three groups of evidence-based interventions on variables thought to be associated with self-regulation. The dependent variables were (a) frequency and duration of behaviors thought to indicate dysregulation, (b) active participation in school activities, and (c) time from onset of behaviors indicating dysregulation until achievement of a calm, regulated state. The interventions, which included provision of meaningful, enjoyable, and interactive activities, anticipatory strategies, and calming strategies, significantly influenced the dependent variables and are described in detail. PMID- 26853070 TI - A method to assess the influence of individual player performance distribution on match outcome in team sports. AB - This study developed a method to determine whether the distribution of individual player performances can be modelled to explain match outcome in team sports, using Australian Rules football as an example. Player-recorded values (converted to a percentage of team total) in 11 commonly reported performance indicators were obtained for all regular season matches played during the 2014 Australian Football League season, with team totals also recorded. Multiple features relating to heuristically determined percentiles for each performance indicator were then extracted for each team and match, along with the outcome (win/loss). A generalised estimating equation model comprising eight key features was developed, explaining match outcome at a median accuracy of 63.9% under 10-fold cross-validation. Lower 75th, 90th and 95th percentile values for team goals and higher 25th and 50th percentile values for disposals were linked with winning. Lower 95th and higher 25th percentile values for Inside 50s and Marks, respectively, were also important contributors. These results provide evidence supporting team strategies which aim to obtain an even spread of goal scorers in Australian Rules football. The method developed in this investigation could be used to quantify the importance of individual contributions to overall team performance in team sports. PMID- 26853071 TI - Quality of chronic kidney disease management in primary care: a retrospective study. AB - BACKGROUND: Early detection and appropriate management of chronic kidney disease (CKD) in primary care are essential to reduce morbidity and mortality. AIM: To assess the quality of care (QoC) of CKD in primary healthcare in relation to patient and practice characteristics in order to tailor improvement strategies. DESIGN AND SETTING: Retrospective study using data between 2008 and 2011 from 47 general practices (207 469 patients of whom 162 562 were adults). METHOD: CKD management of patients under the care of their general practitioner (GP) was qualified using indicators derived from the Dutch interdisciplinary CKD guideline for primary care and nephrology and included (1) monitoring of renal function, albuminuria, blood pressure, and glucose, (2) monitoring of metabolic parameters, and alongside the guideline: (3) recognition of CKD. The outcome indicator was (4) achieving blood pressure targets. Multilevel logistic regression analysis was applied to identify associated patient and practice characteristics. RESULTS: Kidney function or albuminuria data were available for 59 728 adult patients; 9288 patients had CKD, of whom 8794 were under GP care. Monitoring of disease progression was complete in 42% of CKD patients, monitoring of metabolic parameters in 2%, and blood pressure target was reached in 43.1%. GPs documented CKD in 31.4% of CKD patients. High QoC was strongly associated with diabetes, and to a lesser extent with hypertension and male sex. CONCLUSION: Room for improvement was found in all aspects of CKD management. As QoC was higher in patients who received structured diabetes care, future CKD care may profit from more structured primary care management, e.g. according to the chronic care model. KEY POINTS: Quality of care for chronic kidney disease patients in primary care can be improved. In comparison with guideline advice, adequate monitoring of disease progression was observed in 42%, of metabolic parameters in 2%, correct recognition of impaired renal function in 31%, and reaching blood pressure targets in 43% of chronic kidney disease patients. Quality of care was higher in patients with diabetes. Chronic kidney disease management may be improved by developing strategies similar to diabetes care. PMID- 26853072 TI - Underwater robotic suturing. AB - BACKGROUND: Laparoscopic and robotic surgeries have become popular, and this popularity is increasing. However, the environment in which such surgeries are performed is rarely discussed. Similar to arthrosurgery performed in water, artificial ascites could be a new environment for laparoscopic surgery. This study was performed to determine whether robotic surgery is applicable to complicated suturing underwater. MATERIAL AND METHODS: A da Vinci Surgical System S was used. A weighted fabric sheet was placed at the bottom of a tank. Identical sets were made for each environment: One tank was dry, and the other was filled with water. The suturing task involved placement of a running silk suture around the perimeter of a small circle. The task was performed eight times in each environment. The task time and integrity score were determined. The integrity score was calculated by evaluating accuracy, tightness, thread damage, and uniformity; each factor was evaluated using a five-point scale. RESULTS: Although statistically significant differences were not shown in either task time or integrity score between the underwater and air environments, robotic suturing underwater is not inferior to performance in air. CONCLUSIONS: The feasibility of robotic suturing underwater was confirmed under the herein-described experimental conditions. PMID- 26853073 TI - Increased expression of phosphorylated forms of heat-shock protein-27 and p38MAPK in macrophage-rich regions of fibro-fatty atherosclerotic lesions in the rabbit. AB - We aimed to assess the expression and distribution of Hsp27, pHsp27 (Ser82), p38MAPK and p-p38MAPK in fibro-fatty atherosclerotic lesions and the myocardium of hypercholesterolaemic rabbits. Male New Zealand white rabbits were fed a high cholesterol diet for 18 weeks, maintaining serum cholesterol at approximately 20 mmol/l over this period. Aortic arch and myocardial tissues were analysed by Western blot, immunohistochemistry and double immunofluorescence. Plasma Hsp27 levels were measured by ELISA. There was a significant increase in the expression of monomeric and dimeric forms of Hsp27, together with pHsp27 (Ser82), p38MAPK and p-p38MAPK in the fibro-fatty atherosclerotic lesions (P < 0.01; P < 0.05; P < 0.001; and P < 0.001, respectively) and the myocardial tissues (P < 0.001) from the cholesterol-fed rabbits compared with equivalent tissues from controls when the plasma concentration was low. Immunohistochemical analysis of the fibro-fatty lesions showed marked increases in Hsp27 and pHsp27 (Ser82) immunoreactivity. Double immunostaining showed intense expression of pHsp27 and p-p38MAPK in regions that were rich in macrophages, suggesting a close association with these inflammatory cells, whereas, in regions rich in smooth muscle cells, only p p38MAPK was found to be strongly expressed. An increased expression of pHsp27 (Ser82) was spatially associated with increased p-p38MAPK within fibro-fatty atherosclerotic lesions and was colocalized to regions rich in macrophages. The initial increase in plasma Hsp27 levels may reflect the increase in systemic inflammation and oxidative stress in the early phases of disease. The falling concentrations subsequently may be coincident with the development of the advanced atherosclerotic lesions. PMID- 26853074 TI - RNA interference of cytochrome P450 CYP6F subfamily genes affects susceptibility to different insecticides in Locusta migratoria. AB - BACKGROUND: Many insect cytochrome P450s (CYPs) play critical roles in detoxification of insecticides. The CYP6 family is unique to the class Insecta, and its biochemical function has essentially been associated with the metabolism of xenobiotics. In this study, we sequenced and characterised the full-length cDNAs of five CYP genes from Locusta migratoria, a highly destructive agricultural pest worldwide. RESULTS: The five genes were predominantly expressed in brain, guts, fat bodies or Malpighian tubules. CYP6FE1, CYP6FF1 and CYP6FG1 were expressed at higher levels in fourth-instar nymphs than in other developmental stages. CYPFD2 is specifically expressed in adults, whereas CYP6FD1, CYP6FD2 and CYP6FE1 showed significantly lower expression in eggs than in other developmental stages. Deltamethrin suppressed CYP6FD1 expression in third-instar nymphs and upregulated the expression level of CYP6FD2, CYP6FF1 and CYP6FG1 at the dose of LD10 . Efficient RNA interference-mediated gene silencing was established for four of the five CYP genes. Silencing of CYP6FF1 increased the nymphal mortality from 23 to 50% in response to deltamethrin. Silencing of CYP6FD2 and CYP6FE1 increased the nymphal mortality from 32 to 72 and 66%, respectively, to carbaryl. CONCLUSION: Three of the four CYP6F subfamily genes in L. migratoria were associated with the detoxification of deltamethrin or carbaryl. The role of CYPs in insecticide detoxification appears to be both gene and insecticide specific. (c) 2016 Society of Chemical Industry. PMID- 26853075 TI - Direct Estimation of the Surface Location of Immobilized Functional Groups for Concerted Catalysis Using a Probe Molecule. AB - The location of active sites during concerted catalysis by a metal complex and tertiary amine on a SiO2 surface is discussed based on the interaction between the functionalized SiO2 surface and a probe molecule, p-formyl phenylboronic acid. The interactions of the probe molecule with the surface functionalities, diamine ligand, and tertiary amine, were analyzed by FT-IR and solid-state (13)C and (11)B MAS NMR. For the catalyst exhibiting high 1,4-addition activity, the diamine ligand and tertiary amine base exist in closer proximity than in the catalyst with low activity. PMID- 26853076 TI - Use of outcome measures improved after a tailored implementation in primary care physiotherapy: a prospective, controlled study. AB - RATIONALE, AIMS AND OBJECTIVES: It is important that physiotherapists routinely use outcome measures to evaluate treatment results. There is limited knowledge about effective ways to increase use of outcome measures. The objectives were to investigate the effect of a tailored implementation of guidelines for evaluation of physiotherapy treatment and to explore differences in outcome subgrouped by demographic variables. METHODS: A prospective, controlled study was conducted in primary care physiotherapy in western Sweden. 448 publicly employed physiotherapists participated. The intervention comprised a tailored, multi component implementation of guidelines for treatment and evaluation of musculoskeletal disorders. The core component was a 3-hour implementation seminar. The control group received no intervention. Self-reported attitudes towards, access to and use of outcome measures were assessed with a web-based questionnaire before and after the implementation. RESULTS: After the implementation, a significantly higher proportion of physiotherapists in the intervention group than in the control group reported using outcome measures frequently, 54.8% vs. 35.6%, a 19.2% difference. The proportion of physiotherapists who reported that they considered outcome measures important to use and that they had easy access to outcome measures at their workplace, were similar in both groups at follow-up, 92.8% vs. 93.1%, and 95.2% vs. 90.8%, respectively. At follow-up, no differences related to demographic variables were found in the subgroup analyses. CONCLUSIONS: The findings suggest that a tailored, multi-component implementation can be effective in increasing use of outcome measures. Although most physiotherapists considered outcome measures important and reported having easy access to them at their workplace, only a little more than half reported using outcome measures after the intervention. PMID- 26853078 TI - Preface. PMID- 26853077 TI - High-density molecular characterization and association mapping in Ethiopian durum wheat landraces reveals high diversity and potential for wheat breeding. AB - Durum wheat (Triticum turgidum subsp. durum) is a key crop worldwide, and yet, its improvement and adaptation to emerging environmental threats is made difficult by the limited amount of allelic variation included in its elite pool. New allelic diversity may provide novel loci to international crop breeding through quantitative trait loci (QTL) mapping in unexplored material. Here, we report the extensive molecular and phenotypic characterization of hundreds of Ethiopian durum wheat landraces and several Ethiopian improved lines. We test 81 587 markers scoring 30 155 single nucleotide polymorphisms and use them to survey the diversity, structure, and genome-specific variation in the panel. We show the uniqueness of Ethiopian germplasm using a siding collection of Mediterranean durum wheat accessions. We phenotype the Ethiopian panel for ten agronomic traits in two highly diversified Ethiopian environments for two consecutive years and use this information to conduct a genome-wide association study. We identify several loci underpinning agronomic traits of interest, both confirming loci already reported and describing new promising genomic regions. These loci may be efficiently targeted with molecular markers already available to conduct marker assisted selection in Ethiopian and international wheat. We show that Ethiopian durum wheat represents an important and mostly unexplored source of durum wheat diversity. The panel analysed in this study allows the accumulation of QTL mapping experiments, providing the initial step for a quantitative, methodical exploitation of untapped diversity in producing a better wheat. PMID- 26853079 TI - Exploratory transcriptomic analysis in muscle tissue of broilers fed a phytase supplemented diet. AB - The effect of phytase on phosphorus retention, broiler (Gallus gallus) performance and bone mineralization in diets with reduced inorganic phosphate concentration is well documented. Furthermore, so-called 'extra-phosphoric' effects of phytase have been described in the literature that may be associated with changes in mineral and amino acid partitioning and requirements per se. In particular, the role of myo-inositol in phytase responses is implied but not well elucidated. It was the purpose of the experiment reported herein to explore the effect of phytase on broiler growth, nutrient digestibility, blood biochemistry and gene expression. A 5-week broiler floor pen trial was conducted to evaluate the effect of supplementation of a moderately phosphorus-deficient diet with 1000 U/kg of a 6-microbial phytase. Parameters measured were growth performance, phosphorus (P), calcium (Ca) and myo-inositol plasma concentrations, apparent ileal P digestibility, bone mineralization, breast meat weight and Pectoralis major muscle transcriptome. Supplementation of the diet with phytase improved weight gain during the starter period (18%) and the whole period (24%) compared with animals that received the control diet (p < 0.05). Improved feed conversion ratio, increased myo-inositol plasma concentration, tibia ash contents and breast meat weight were also observed in animals fed phytase. The transcriptomic analysis revealed that some differentially expressed genes (DEG) in broilers, receiving phytase in comparison with animals fed reduced phosphorus diet without phytase, were part of pathways involved in muscle development, via calmodulin/calcineurin and insulin-like growth factor. Microarray data confirmation was performed on six genes by quantitative PCR (qPCR): PI3K regulatory and catalytic subunit, Phospholipase C beta, Myocyte Enhancer Factors 2A and 2C, and calcineurin A. The results suggested that dietary supplementation with this phytase could generate low molecular weight phytate esters and indirectly myo-inositol, and could help us to understand how muscle metabolism may be affected at a gene level. PMID- 26853080 TI - Nano/Micro-Structured Si/C Anodes with High Initial Coulombic Efficiency in Li Ion Batteries. AB - One of the major challenges for designing high-capacity anode materials is to combine both Coulombic efficiency and cycling stability. Herein, nano/micro structured Si/C composites are designed and synthesized to address this challenge by decreasing the specific surface area and improving the tap density of Si/C materials. An ultrahigh initial Coulombic efficiency of 91.2 % could be achieved due to a proper particle size, low specific surface area, and optimized structure. The nano/micro-structured Si/C anodes exhibit excellent cycling stability with 96.5 % capacity retention after 100 cycles under a current density of 0.2 A g(-1) . PMID- 26853081 TI - Expanding the modular ester fermentative pathways for combinatorial biosynthesis of esters from volatile organic acids. AB - Volatile organic acids are byproducts of fermentative metabolism, for example, anaerobic digestion of lignocellulosic biomass or organic wastes, and are often times undesired inhibiting cell growth and reducing directed formation of the desired products. Here, we devised a general framework for upgrading these volatile organic acids to high-value esters that can be used as flavors, fragrances, solvents, and biofuels. This framework employs the acid-to-ester modules, consisting of an AAT (alcohol acyltransferase) plus ACT (acyl CoA transferase) submodule and an alcohol submodule, for co-fermentation of sugars and organic acids to acyl CoAs and alcohols to form a combinatorial library of esters. By assembling these modules with the engineered Escherichia coli modular chassis cell, we developed microbial manufacturing platforms to perform the following functions: (i) rapid in vivo screening of novel AATs for their catalytic activities; (ii) expanding combinatorial biosynthesis of unique fermentative esters; and (iii) upgrading volatile organic acids to esters using single or mixed cell cultures. To demonstrate this framework, we screened for a set of five unique and divergent AATs from multiple species, and were able to determine their novel activities as well as produce a library of 12 out of the 13 expected esters from co-fermentation of sugars and (C2-C6) volatile organic acids. We envision the developed framework to be valuable for in vivo characterization of a repertoire of not-well-characterized natural AATs, expanding the combinatorial biosynthesis of fermentative esters, and upgrading volatile organic acids to high-value esters. Biotechnol. Bioeng. 2016;113: 1764 1776. (c) 2016 Wiley Periodicals, Inc. PMID- 26853083 TI - Limited information estimation of the diffusion-based item response theory model for responses and response times. AB - Psychological tests are usually analysed with item response models. Recently, some alternative measurement models have been proposed that were derived from cognitive process models developed in experimental psychology. These models consider the responses but also the response times of the test takers. Two such models are the Q-diffusion model and the D-diffusion model. Both models can be calibrated with the diffIRT package of the R statistical environment via marginal maximum likelihood (MML) estimation. In this manuscript, an alternative approach to model calibration is proposed. The approach is based on weighted least squares estimation and parallels the standard estimation approach in structural equation modelling. Estimates are determined by minimizing the discrepancy between the observed and the implied covariance matrix. The estimator is simple to implement, consistent, and asymptotically normally distributed. Least squares estimation also provides a test of model fit by comparing the observed and implied covariance matrix. The estimator and the test of model fit are evaluated in a simulation study. Although parameter recovery is good, the estimator is less efficient than the MML estimator. PMID- 26853082 TI - Treatment of Chronic inflammatory polyneuropathy may improve associated hearing loss: a case report and review of The literature. PMID- 26853084 TI - The natural course of congenital nasal pyriform aperture stenosis. AB - OBJECTIVES/HYPOTHESIS: Patients with congenital nasal pyriform aperture stenosis (CNPAS) may become less symptomatic with age. Therefore, we aimed to develop a growth curve of the pyriform aperture so that a more comprehensive plan can be designed for CNPAS patients who show little response to conservative treatment. STUDY DESIGN: A single-institution study, retrospective review of CNPAS patients during the period November 1997 to December 2014. METHODS: We measured the distances between the bilateral nasal processes of the maxilla (interprocess distance [IPD]) on three-dimensional computed tomography images and then divided the patients into five different age groups. A growth curve of the pyriform aperture was then constructed based on the distance-age relationship. RESULTS: Fifty-four IPD measurements were included. The mean IPD was 3.57 mm in neonates < 1 month old, 4.08 mm in infants aged 1 to 3 months, 5.19 mm in the 4-month to 11 month age group, 6.61 mm in the 12-month to 36-month age group, and 9.20 mm in children > 36 months of age. We found that the cubic curve was the most appropriate growth curve, and that growth tended to be slower from 3.5 years to 6 years of age. CONCLUSIONS: The growth curve of the pyriform aperture in children with CNPAS developed in this study can aid in treatment planning and predict clinical outcome of CNPAS patients. Although CNPAS patients may become less symptomatic with age, when the observed IPD falls progressively farther from the curve, more aggressive intervention should be considered, such as changing the management strategy from observation to conservative treatment or from conservative treatment to surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2399 2402, 2016. PMID- 26853085 TI - Indomethacin Responsive Headaches: Exhaustive Systematic Review with Pooled Analysis and Critical Appraisal of 81 Published Clinical Studies. AB - OBJECTIVES: The relationship between indomethacin (IMC) and headache treatment has long intrigued clinicians and clinical researchers in Headache Medicine. Why is it efficacious in many types of headache disorders when other medications are not, and what is the mechanism behind its efficacy? IMC and headache related topics that have been explored in detail in the literature include IMC-responsive headache disorders ("traditional"), pharmacology of IMC, symptomatic headaches responsive to IMC, "novel" headache conditions that respond, cluster headache and IMC, IMC provoking headache, the issue about" absolute" and "non-absolute" effect of IMC on headache disorders, and the morphing trigeminal autonomic cephalalgias (TACs). DATA SOURCE: A PubMed/MEDLINE search was used for Clinical Studies Categories and Systematic Reviews on the PubMed Clinical Queries. The search details were "indomethacin" AND "headache" spanning all previous years until February 1, 2015. Methods were in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. REVIEW METHODS: Articles were excluded if IMC had not been used to treat headache disorders in adults, if the article concerned IMC-responsive headaches but made no reference to the use of IMC, and articles not addressing the above mentioned topics. RESULTS AND CONCLUSIONS: The "velocity" of publications on IMC and headache seems to be decreasing, particularly on the use of IMC for the treatment of TACs. The science behind the understanding of the putative mechanisms of IMC's action on headache has moved forward, but the answer to why it works better than other nonsteroidal anti-inflammatory drugs has been elusive. There are case reports of other rare headache disorders that may be responsive to IMC. The dosages of IMC used as a tool for detecting IMC responsive disorders vary according to different centers of investigation. In many circumstances, headache disorders similar to "primary" IMC-responsive disorders are actually symptomatic disorders. Cluster headache as an IMC-resistant headache disorder may not be as absolute as once thought. Sometimes, IMC has been found to provoke headache; differentiating IMC-provoked headache from IMC-resistant headache can make headache diagnosis and management difficult. As for the "absolute" responsiveness of IMC, it is possible that using higher dosages leads to higher sensitivity, probably at the expense of decreased specificity. There are many reports about the occurrence of two or more IMC responsive disorders (latu sensu) in the same patient, which may be coincidental. PMID- 26853086 TI - Walking as a social practice: dispersed walking and the organisation of everyday practices. AB - This paper uses social practice theory to study the interweaving of walking into everyday practices and considers how greater awareness of everyday walking can influence its position within the organisation and scheduling of everyday life. Walking is of policy interest because of its perceived benefits for health. This paper asserts that increased awareness of everyday walking allows users to become more active without having to reschedule existing activities. Using Schatzki's distinction between dispersed and integrative practices, it argues that increasing awareness of dispersed walking can enlist walking into the teleoaffective organisation of some social practices and prompt the performance of new 'health practices' within everyday domains of life such as shopping and employment. While this analysis offers useful insights for the design of behaviour change strategies, it also points to some unintended consequences of using digital feedback to increase walking awareness. In directing the gaze of participants at one particular element of their daily practices, the paper suggests, digital walking feedback provides a 'partial' view of practices: by highlighting the exercise value of walking at the expense of other values it can prompt feedback recipients to pass moral judgements on themselves based on this partial view. A Virtual Abstract of this paper can be found at: https://youtu.be/WV7DUnKD5Mw. PMID- 26853087 TI - Structural Evolution of an Organic Semiconducting Molecule onto a Soft Substrate. AB - The structural organization and evolution of the organic semiconducting molecule 2,7-dioctyloxy[1]benzothieno[3,2-b]-benzothiophene on a soft matrix is studied. Thin films of a blend formed from polystyrene and the molecule were prepared by spin-coating onto silicon substrates, which were subsequently studied by using a combination of microscopy and scattering techniques. The organic semiconducting molecule segregated to the surface and developed a phase with a different structure to the bulk, as in the case of a substrate induced phase observed previously. Under a solvent vapor annealing procedure, the growth of micrometer sized tetragonal crystals onto the polymer surface was observed, which was not evidenced for the silicon substrates. PMID- 26853089 TI - Sperm traits differ between winged and wingless males of the ant Cardiocondyla obscurior. AB - Size and shape of sperm cells vary tremendously throughout the animal kingdom. The adaptive significance of this variation is not fully understood. In addition to sperm-female interactions and the environmental conditions, the risk of sperm competition might affect number, morphology and other "quality" traits of sperm. In the male-diphenic ant Cardiocondyla obscurior, winged sneaker males have limited sperm number, because their testes degenerate shortly after adult emergence, as is typical for males of social Hymenoptera. In contrast, wingless fighter males continuously replenish their sperm supply due to their exceptional lifelong spermatogenesis. While winged males usually have to compete with several other winged males for virgin queens, wingless males are able to monopolize queens by killing all other rivals. Hence, this presents a unique system to investigate how alternative reproductive tactics and associated physiology affect sperm morphology and viability. We found that sperm-limited males invest into sperm number instead of sperm size. Variance in sperm length is smaller in winged males, probably reflecting that they have to compete with several other males. Finally, sperm viability is equally high in both male phenotypes. PMID- 26853088 TI - Synthesis of a [(18)F]-labeled ceritinib analogue for positron emission tomography of anaplastic lymphoma kinase, a receptor tyrosine kinase, in lung cancer. AB - Anaplastic lymphoma kinase (ALK), an oncogenic receptor tyrosine kinase, has emerged as a therapeutic target in solid and hematologic tumors. Although several ALK inhibitors have gained recent approval for therapy, non-invasive indicators of target engagement or for use as predictive biomarkers in vivo are lacking. Therefore, we designed and synthesized a radiolabeled analogue of the ALK inhibitor ceritinib, [(18)F]fluoroethyl-ceritinib ([(18)F]-FEC), for use with positron emission tomography. We used two methods to synthesize [(18)F]-FEC. First, [(18)F]fluoroethyl-tosylate was prepared, coupled with ceritinib, and the product purified to yield [(18)F]-FEC. Alternatively, a precursor compound was synthesized, directly fluorinated with (18)F-fluoride, and purified to yield [(18)F]-FEC. The first method produced [(18)F]-FEC with an average decay corrected yield of 24% (n = 4), specific activity of 1200 mCi/umol, and >99% purity; synthesis time was 115 min from the end of bombardment. The second method produced [(18)F]-FEC with an average yield of 7% (n = 4), specific activity of 1500 mCi/umol, and >99% purity; synthesis time was 65 min from the end of bombardment. The synthesis of a novel (18)F-labeled analogue of ceritinib has been achieved in acceptable yields, at high purity, and with high specific activity. The compound is a potential positron emission tomography imaging agent for the detection of ALK-overexpressing solid tumors such as lung cancer. PMID- 26853090 TI - Reinforcing the association between distal 1q CNVs and structural brain disorder: A case of a complex 1q43-q44 CNV and a review of the literature. AB - Copy Number Variations (CNVs) comprising the distal 1q region 1q43-q44 are associated with neurological impairments, structural brain disorder, and intellectual disability. Here, we report an extremely rare, de novo case of a 1q43-q44 deletion with an adjacent duplication, associated with severe seizures, microcephaly, agenesis of the corpus callosum, and pachygyria, a consequence of defective neuronal migration disorder. We conducted a literature survey to find that our patient is only the second case of such a 1q43-q44 CNV ever to be described. Our data support an association between 1q43-q44 deletions and microcephaly, as well as an association between 1q43-q44 duplications and macrocephaly. We compare and contrast our findings with previous studies reporting on critical 1q43-q44 regions and their constituent genes associated with seizures, microcephaly, and corpus callosum abnormalities [Ballif et al., 2012; Hum Genet 131:145-156; Nagamani et al., 2012; Eur J Hum Genet 20:176-179]. Taken together, our study reinforces the association between 1q43-q44 CNVs and brain disorder. PMID- 26853091 TI - Neurologic cues modulate immune-mediated liver injury and regeneration. PMID- 26853092 TI - Synthesis and Application of C2 and C3 Symmetric (R)-Phenylglycinol-Derived Chiral Stationary Phases. AB - A C3 symmetric (R)-phenylglycinol N-1,3,5-benzenetricarboxylic acid-derived chiral stationary phase (CSP) and three C2 symmetric (R)-phenylglycinol CSPs were newly synthesized using o-, m-, and p-phthaloyl dichlorides. These CSPs were used to compare the resolution of 25 chiral samples using a previously reported 3,5 dinitrobenzoyl (R)-phenylglycinol-derived CSP. Even though all CSPs have the same chiral moiety, the C3 symmetric CSP showed the best resolution. PMID- 26853093 TI - The Role of TCD in the Evaluation of Acute Stroke. AB - BACKGROUND: The additional information that transcranial Doppler (TCD) can provide as part of a multimodal imaging stroke protocol in the setting of hyper acute strokes has not been evaluated. METHODS: Consecutive patients admitted between December 2012 and January 2015 with ischemic stroke of less than 4.5 hours of onset were studied as soon as possible with a protocol consisting of noncontrast brain computed tomography, computed tomography angiography of supra aortic vessels, diffusion-weighted magnetic resonance imaging, and TCD. RESULTS: Eighty-six patients were included. The imaging protocol was performed 113.9 (+/ 23) minutes after the stroke symptoms appeared and by TCD after 150.2 (+/-19) minutes. Sixty-six (76.7%) patients were treated with revascularization therapies. TCD provided additional information in 49 cases (56.9.4%, 95 CI 46.4 66.9). More than one piece of additional information was obtained in 17 patients. The most frequent additional information was collateral pathways, information related to patency of vessels, and active microembolization. Multivariate analysis demonstrated that, intracranial vessel occlusion (P <.001) and optimal sonographic windows (P <.004) were the variables associated with additional information. In 15 patients (17.4%; 95 CI 9.4-25.5) the additional information changed the management. In 8 patients endovascular rescue was applied after the failure of intravenous thrombolysis; in 5 patients angiography was suspended and in 2 other cases aggressive neurocritical care was indicated. CONCLUSIONS: TCD in the first 4.5 hours of acute ischemia can provide additional information to a multimodal acute ischemic stroke imaging protocol, and can induce changes in the management of a proportion of these patients. PMID- 26853094 TI - Integrating omics to unravel the stress-response mechanisms in probiotic bacteria: Approaches, challenges, and prospects. AB - Identifying the stress-response mechanism of probiotic bacteria has always captivated the interest of food producers. It is crucial to identify probiotic bacteria that have increased stress tolerance to survive during production, processing, and storage of food products. However, in order to achieve high resistance to environmental factors, there is a need to better understand stress induced responses and adaptive mechanisms. With advances in bacterial genomics, there has been an upsurge in the application of other omic platforms such as transcriptomics, proteomics, metabolomics, and some more recent ones such as interactomics, fluxomics, and phenomics. These omic technologies have revolutionized the functional genomics and their application. There have been several studies implementing various omic technologies to investigate the stress responses of probiotic bacteria. Integrated omics has the potential to provide in depth information about the mechanisms of stress-induced responses in bacteria. However, there remain challenges in integrating information from different omic platforms. This review discusses current omic techniques and challenges faced in integrating various omic platforms with focus on their use in stress-response studies. PMID- 26853095 TI - Otitis media with effusion: benefits and harms of strategies in use for treatment and prevention. AB - Otitis media with effusion (OME) is a common clinical condition that is associated with hearing loss. It can be diagnosed at least once in approximately 80% of preschool children: 30-40% of them have recurrent episodes, and 5-10% have chronic disease. OME, in recurrent and persistent cases, might significantly delay or impair communication skills, resulting in behavioral and educational difficulties. Several therapeutic approaches have been used to avoid these problems. Most, however, have not been adequately studied, and no definitive conclusions can be drawn. Official guidelines do not recommend the use of decongestants, antihistamines, steroids, or antibiotics. The data are too scanty to assess other interventions, although autoinflation, because it incurs neither cost nor adverse events, deserves attention. Surgical procedures (i.e., tympanostomy tube insertion and adenoidectomy as an adjuvant) can be useful in some cases. This review evaluates all the current OME treatments and preventive measures, including their possible adverse events. PMID- 26853096 TI - The cost of cancer: a retrospective analysis of the financial impact of cancer on young adults. AB - Young adult cancer survivors (YAs) are confronted with immense financial challenges in the wake of their treatment. Medical bills and loss of savings may cause YAs to forgo recommended medications or follow-up appointments. Young survivors with financial concerns also report depression, stress and anxiety. The Samfund is a national nonprofit organization that provides financial support to YAs post-treatment. To quantify the financial burden of cancer in YAs, a retrospective analysis was performed of data collected from Samfund grant applications of 334 YA cancer survivors. Grants were awarded between 2007 and 2013 and grant recipients were consented electronically in 2014 for retrospective data analysis. Recipients ranged from 19 to 39 years of age at the time of their grant applications. Descriptive statistics were calculated and compared to the Medical Expenditure Panel Survey (MEPS) and U.S. census data on age-matched peers. Financial indicators of YA cancer survivors are worse in many domains than those of age-matched controls. Furthermore, YA survivors in their 30s report more perilous prefunding financial situations than younger grant recipients. Cancer has a devastating and age-specific impact on the finances of YAs. Philanthropic grants from the cancer support community, in conjunction with healthcare policy reforms, have the potential to break the cycle of financial need and help YAs move forward with their lives after cancer treatment. PMID- 26853097 TI - Acute coronary angiography after coronary artery bypass grafting. AB - OBJECTIVES: Coronary angiography is the golden standard when myocardial ischemia after CABG occurs. We summarize our experience of acute coronary angiography after CABG. DESIGN: All 4446 patients (mean age 68 +/- 9 years, 22% women) who underwent CABG 2007 to 2012 were included in this retrospective observational study. Incidence, indications, findings, measures of acute angiography after CABG was assessed. Outcome variables were compared between patients who underwent angiography and those who did not. RESULTS: Eighty-seven patients (2%) underwent acute coronary angiography. Patients undergoing angiography had ECG changes (92%), echocardiographic alterations (48%), hemodynamic instability (28%), angina (15%), and/or arrhythmia (13%). Positive findings were detected in 69% of the cases. Only ECG changes as indication for angiography had a moderate association with positive findings, but the precision increased if other sign(s) of ischemia were present. Thirty-day mortality (7% versus 2%, p = 0.002) was higher and long term-cumulative survival lower (77% versus 87% at five years, p = 0.043) in angiography patients. CONCLUSIONS: Acute angiography is a rare event after CABG. Postoperative myocardial ischemia leading to acute coronary angiography is associated with increased short-term and long-term mortality. PMID- 26853098 TI - Development of role-related minimum cardiorespiratory fitness standards for firefighters and commanders. AB - A minimum cardiorespiratory fitness standard was derived for firefighters following a metabolic demands analysis. Design and minimal acceptable performance of generic firefighting task simulations (i.e. hose running, casualty evacuation, stair climb, equipment carry, wild-land fire) were endorsed by a panel of operationally experienced experts. Sixty-two UK firefighters completed these tasks wearing a standard protective firefighting ensemble while being monitored for peak steady-state metabolic demand and cardiovascular strain. Four tasks, endorsed as valid operational simulations by >=90% of participants (excluding wild-land fire; 84%), were deemed to be a sufficiently valid and reliable basis for a fitness standard. These tasks elicited an average peak steady-state metabolic cost of 38.1 +/- 7.8 ml kg-1 min-1. It is estimated that healthy adults can sustain the total duration of these tasks (~16 min) at <=90% maximum oxygen uptake and a cardiorespiratory fitness standard of >=42.3 ml kg-1 min-1 would be required to sustain work. Practitioner Summary: A cardiorespiratory fitness standard for firefighters of >=42.3 ml kg-1 min-1 was derived from monitoring minimum acceptable performance of essential tasks. This study supports the implementation of a routine assessment of this fitness standard for all UK operational firefighters, to ensure safe physical preparedness for occupational performance. PMID- 26853100 TI - Retraction note: Correlation Between High-Density Lipoprotein and Monocyte Subsets in Patients with Stable Coronary Heart Disease. AB - In the article entitled, "Correlation Between High-Density Lipoprotein and Monocyte Subsets in Patients with Stable Coronary Heart Disease" which was published in Medical Science Monitor 2015;21: 3129-3135, sections in the text have been directly copied from a previously published article, entitled, "Small high-density lipoprotein is associated with monocyte subsets in stable coronary artery disease", Krychtiuk KA, Kastl SP, Pfaffenberger S, Pongratz T, Hofbauer SL, Wonnerth A, Katsaros KM, Goliasch G, Gaspar L, Huber K, Maurer G, Dostal E, Oravec S, Wojta J, Speidl WS in Atherosclerosis 2014 Dec;237(2):589-96. Thus owing to duplicity of text, the article is being retracted. Reference: 1. Shaoyan Jiang, Dan Li, Jian Li, Yi An Correlation Between High-Density Lipoprotein and Monocyte Subsets in Patients with Stable Coronary Heart Disease Medical Science Monitor 2015;21: 3129-3135 DOI 10.12659/MSM.894485. PMID- 26853099 TI - Three wall-associated kinases required for rice basal immunity form protein complexes in the plasma membrane. AB - Receptor-like kinases (RLKs) play key roles in disease resistance, in particular basal immunity. They recognize patterns produced by the pathogen invasion and often work as complexes in the plasma membrane. Among these RLKs, there is increasing evidence in several plant species of the key role of Wall-associated kinases (WAKs) in disease resistance. We recently showed using rice (Oryza sativa) loss-of-function mutants of three transcriptionally co-regulated OsWAK genes that individual OsWAKs are positively required for quantitative resistance to the rice blast fungus, Magnaporthe oryzae. This finding was unexpected since WAK genes belong to large gene families where functional redundancy is expected. Here we provide evidence that this may be due to complex physical interaction between OsWAK proteins. PMID- 26853101 TI - The General Public's Awareness of Early Symptoms of and Emergency Responses to Acute Myocardial Infarction and Related Factors in South Korea: A National Public Telephone Survey. AB - BACKGROUND: Prompt treatment affects prognosis and survival after acute myocardial infarction (AMI) onset. This study evaluated the awareness of early symptoms of AMI and knowledge of appropriate responses on symptom occurrence, along with related factors. METHODS: Participants' knowledge of the early symptoms of and responses to AMI onset were investigated using a random digit dialing survey. We included 9600 residents of 16 metropolitan cities and provinces in Korea. RESULTS: The proportions of respondents who were aware of early symptoms of AMI ranged from 32.9% (arm or shoulder pain) to 79.1% (chest pain and discomfort). Of the respondents, 67.0% would call an ambulance if someone showed signs of AMI, 88.7% knew >=1 symptom, 10.9% knew all five symptoms, and 3.1% had excellent knowledge (correct identification of all five AMI symptoms, not answering "Yes" to the trap question, and correctly identifying calling an ambulance as the appropriate response when someone is exhibiting AMI symptoms). The odds ratio (OR) for having excellent knowledge was significantly higher for those who graduated college or higher (OR 3.42; 95% confidence interval [CI], 1.09-10.76) than for those with less than a primary school education, as well as for subjects with AMI advertisement exposure (OR 1.49; 95% CI, 1.10-2.02) and with knowledge of AMI (OR 1.63; 95% CI, 1.16-2.27). The 60- to 79-year-old group had significantly lower OR for excellent knowledge than the 20- to 39-year-old group (OR 0.53; 95% CI, 0.28-0.99). CONCLUSIONS: Awareness of AMI symptoms and the appropriate action to take after symptom onset in South Korea was poor. Therefore, educational and promotional strategies to increase the overall awareness in the general public, especially in the elderly and those with low education levels, are needed. PMID- 26853102 TI - Percentage-Method Improves Properties of Workers' Sitting- and Walking-Time Questionnaire. AB - BACKGROUND: Does asking for the percentage of time spent sitting during work (P method) instead of asking for the absolute length of time spent sitting (T method) improve properties of the workers' sitting- and walking-time questionnaire (WSWQ)? The purpose of this study was to investigate whether questioning technique influences test-retest reliability and criterion validity of the WSWQ. METHODS: Sixty-five Japanese workers completed each version of the WSWQ in random order. Both questionnaires assessed quantities of time spent sitting or walking (including standing) during work time, non-working time on a workday, and anytime on a non-workday. Participants wore the thigh-worn inclinometer (activPAL) as criterion measure. Intraclass correlation coefficients (ICC) and Spearman's rho were used for the analyses. RESULTS: For all three domains, values of reliability and validity with the P-method tended to be higher than with the T-method: ICC values ranged from 0.48-0.85 for the T-method and from 0.71-0.85 for the P-method; Spearman's rho values ranged from 0.25-0.58 for the T-method and from 0.42-0.65 for the P-method. The validities with both methods on a workday (0.51-0.58 for the T-method and 0.56-0.65 for the P-method) were higher than validities on a non-workday (0.25-0.45 for the T-method and 0.42 0.60 for the P-method). In post-survey interviews, 48 participants (77%) chose the P-method as their preferred questioning style. CONCLUSIONS: The study revealed that the P-method WSWQ had better reliability, validity, and ease of answering than the T-method, suggesting that the P-method can improve properties of the WSWQ and consequently advance the quality of epidemiological surveys in this field. PMID- 26853103 TI - Bioluminescent imaging of ABCG2 efflux activity at the blood-placenta barrier. AB - Physiologic barriers such as the blood placenta barrier (BPB) and the blood brain barrier protect the underlying parenchyma from pathogens and toxins. ATP-binding cassette (ABC) transporters are transmembrane proteins found at these barriers, and function to efflux xenobiotics and maintain chemical homeostasis. Despite the plethora of ex vivo and in vitro data showing the function and expression of ABC transporters, no imaging modality exists to study ABC transporter activity in vivo at the BPB. In the present study, we show that in vitro models of the placenta possess ABCG2 activity and can specifically transport D-luciferin, the endogenous substrate of firefly luciferase. To test ABCG2 transport activity at the BPB, we devised a breeding strategy to generate a bioluminescent pregnant mouse model to demonstrate transporter function in vivo. We found that coadministering the ABCG2 inhibitors Ko143 and gefitinib with D-luciferin increased bioluminescent signal from fetuses and placentae, whereas the control P gp inhibitor DCPQ had no effect. We believe that our bioluminescent pregnant mouse model will facilitate greater understanding of the BPB and ABCG2 activity in health and disease. PMID- 26853105 TI - Enhancing capacitance behaviour of CoOOH nanostructures using transition metal dopants by ambient oxidation. AB - Cobalt hydrate and doped binary Co0.9M0.1OOH (M = Ni, Mn, Fe) nanorings of 100 300 nm were fabricated in solution through a facile ambient oxidation method. A transformation from Co0.9Ni0.1(OH)2 nanodiscs to hollow Co0.9Ni0.1OOH nanorings was observed with prolonged reaction time. Core-shell nanodiscs have elemental segregation with a Co(OH)2 core and Ni(OH)2 shell. Co0.9Ni0.1OOH nanorings displayed a higher electrochemical capacitance than Mn and Fe doped nanorings materials or materials with disc-like geometries. PMID- 26853104 TI - Citrus bergamia Juice Extract Attenuates beta-Amyloid-Induced Pro-Inflammatory Activation of THP-1 Cells Through MAPK and AP-1 Pathways. AB - Flavonoids have been shown to be effective in protecting against age-related cognitive and motor decline in both in vitro and in vivo models. Recently, a flavonoid-rich extract of Citrus bergamia juice (BJe) has been shown to display anti-oxidant and anti-inflammatory properties against LPS-induced activation of human THP-1 monocytes. In the light of these observations, we wondered whether BJe may be beneficial against neuroinflammatory processes, such as those observed in Alzheimer's disease. To this aim we used THP-1 monocytes to investigate the mechanisms underlying the beneficial potential of BJe against amyloid-beta1-42 (Abeta1-42) -mediated inflammation. Exposure of THP-1 cells to Abeta1-42 significantly induced the expression and secretion of IL-6 and IL-1beta in THP-1 cells and increased the phosphorylation of ERK 1/2 as well as p46 and p54 members of JNK family. Moreover, Abeta1-42 raises AP-1 DNA binding activity in THP-1 treated cells. Interestingly, all these effects were reduced in the presence of BJe. Our data indicate that BJe may effectively counteract the pro-inflammatory activation of monocytes/microglial cells exposed to amyloid fibrils, suggesting a promising role as a natural drug against neuroinflammatory processes. PMID- 26853106 TI - Development and cross-species transferability of EST-SSR markers in Siberian wildrye (Elymus sibiricus L.) using Illumina sequencing. AB - Siberian wildrye (Elymus sibiricus L.) is a perennial, self-fertilizing grass that plays an important role in animal husbandry and environmental sustenance. However, the transcriptomic and genomic information on this species is very limited, which hinders genetic and breeding studies. In the present study, 76,686,804 clean reads were generated from 11 different tissue samples of E. sibiricus by Illumina paired-end sequencing, and the reads were deposited into the NCBI SRA database (SRX574376). A total of 8,769 EST-SSRs were identified from 94,458 unigene sequences, which were obtained by de novo assembly. Moreover, 1,078 primer pairs were successfully designed, and 500 pairs were randomly selected to assess polymorphisms in 15 E. sibiricus accessions. A total of 112 primer pairs were polymorphic, and the polymorphism information content (PIC) values ranged from 0.39 to 0.81, indicating a high level of informativeness. Furthermore, these 112 polymorphic primer pairs were used to evaluate the transferability to 13 other related species, and 55 EST-SSR markers were found to be polymorphic among these 13 Elymus species. This study collected the global sequence data for E. sibiricus, and the newly developed markers will prove valuable in facilitating genetic diversity in E. sibiricus and related Elymus species. PMID- 26853107 TI - First-Principles Investigation to Ionization of Argon Under Conditions Close to Typical Sonoluminescence Experiments. AB - Mott effect, featured by a sharp increase of ionization, is one of the unique properties of partially ionized plasmas, and thus of great interest to astrophysics and inertial confinement fusion. Recent experiments of single bubble sonoluminescence (SBSL) revealed that strong ionization took place at a density two orders lower than usual theoretical expectation. We show from the perspective of electronic structures that the strong ionization is unlikely the result of Mott effect in a pure argon plasma. Instead, first-principles calculations suggest that other ion species from aqueous environments can energetically fit in the gap between the continuum and the top of occupied states of argon, making the Mott effect possible. These results would help to clarify the relationship between SBSL and Mott effect, and further to gain an better understanding of partially ionized plasmas. PMID- 26853108 TI - The novel adipokine progranulin counteracts IL-1 and TLR4-driven inflammatory response in human and murine chondrocytes via TNFR1. AB - Progranulin (PGRN) is a recently identified adipokine that is supposed to have anti-inflammatory actions. The proinflammatory cytokine interleukin-1beta (IL1beta) stimulates several mediators of cartilage degradation. Toll like receptor-4 (TLR4) can bind to various damage-associated molecular patterns, leading to inflammatory condition. So far, no data exist of PGRN effects in inflammatory conditions induced by IL1beta or lipopolysaccharide (LPS). Here, we investigated the anti-inflammatory potential of PGRN in IL1beta- or LPS-induced inflammatory responses of chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with PGRN in presence or not of IL1beta or LPS. First, we showed that recombinant PGRN had no effects on cell viability. We present evidence that PGRN expression was increased during the differentiation of ATDC-5 cell line. Moreover, PGRN mRNA and protein expression is increased in cartilage, synovial and infrapatellar fat pad tissue samples from OA patients. PGRN mRNA levels are upregulated under TNFalpha and IL1beta stimulation. Our data showed that PGRN is able to significantly counteract the IL1beta-induced expression of NOS2, COX2, MMP13 and VCAM-1. LPS-induced expression of NOS2 is also decreased by PGRN. These effects are mediated, at least in part, through TNFR1. Taken together, our results suggest that PGRN has a clear anti-inflammatory function. PMID- 26853109 TI - 24-Hour Ambulatory Blood Pressure Monitoring in SWEDDs Patients With Parkinsonism. AB - BACKGROUND: Patients diagnosed with Parkinson's disease (PD) on clinics who subsequently turn out to have normal dopamine transporter images have been referred to as scans without evidence of dopaminergic deficits (SWEDDs) patients. Cardiovascular autonomic dysfunction has frequently been reported in PD. In this study, we determined the similarities and differences in cardiac autonomic dysfunction between SWEDDs and PD patients. This study investigated whether 24 hour ambulatory blood pressure monitoring (24-hour ABPM) can help identify possible cases with SWEDDs. METHODS: We enrolled 28 SWEDDs patients, 46 patients with PD, and 30 healthy controls. To evaluate cardiac autonomic function, 24-hour ABPM was performed on all subjects. Cardiac metaiodobenzylguanidine (MIBG) scintigraphy was performed on the SWEDDs and PD subjects. RESULTS: The percentage nocturnal decline in blood pressure differed significantly among SWEDDs patients, PD patients, and controls (p<0.05). In addition to the abnormal nocturnal BP, regulation (nondipping and reverse dipping) was significantly higher in SWEDDs and PD subjects than in the control subjects (p<0.05). There was no significant correlation between the % nocturnal blood pressure reduction and parameters of cardiac MIBG uptake ratio. However, orthostatic hypotension was significant correlated with the nocturnal blood pressure dip (%), nocturnal blood pressure patterns, and the cardiac MIBG uptake ratio (early and late) in combined SWEDDs and PD subjects. CONCLUSIONS: Pathologic nocturnal blood pressure regulation and nocturnal hypertension, known characteristics of PD, are also present in SWEDDs. Moreover, cardiac sympathetic denervation should not be attributed to cardiac autonomic dysfunction in SWEDDs patients. As with PD patients, the SWEDDs patients studied here tended to have cardiac autonomic dysfunction. PMID- 26853110 TI - The effect of helminth infection on the microbial composition and structure of the caprine abomasal microbiome. AB - Haemonchus contortus is arguably the most injurious helminth parasite for small ruminants. We characterized the impact of H. contortus infection on the caprine abomasal microbiome. Fourteen parasite naive goats were inoculated with 5,000 H. contortus infective larvae and followed for 50 days. Six age-matched naive goats served as uninfected controls. Reduced bodyweight gain and a significant increase in the abosamal pH was observed in infected goats compared to uninfected controls. Infection also increased the bacterial load while reducing the abundance of the Archaea in the abomasum but did not appear to affect microbial diversity. Nevertheless, the infection altered the abundance of approximately 19% of the 432 species-level operational taxonomic units (OTU) detected per sample. A total of 30 taxa displayed a significantly different abundance between control and infected goats. Furthermore, the infection resulted in a distinct difference in the microbiome structure. As many as 8 KEGG pathways were predicted to be significantly affected by infection. In addition, H. contortus-induced changes in butyrate producing bacteria could regulate mucosal inflammation and tissue repair. Our results provided insight into physiological consequences of helminth infection in small ruminants and could facilitate the development of novel control strategies to improve animal and human health. PMID- 26853111 TI - Anti-inflammatory Cerebrosides from Cultivated Cordyceps militaris. AB - Cordyceps militaris (bei-chong-chaw, northern worm grass) is a precious and edible entomopathogenic fungus, which is widely used in traditional Chinese medicine (TCM) as a general booster for the nervous system, metabolism, and immunity. Saccharides, nucleosides, mannitol, and sterols were isolated from this fungus. The biological activity of C. militaris was attributed to the saccharide and nucleoside contents. In this study, the aqueous methanolic fraction of C. militaris fruiting bodies exhibited a significant anti-inflammatory activity. Bioactivity-guided fractionation of the active fraction led to the isolation of eight compounds, including one new and two known cerebrosides (ceramide derivatives), two nucleosides, and three sterols. Cordycerebroside A (1), the new cerebroside, along with soyacerebroside I (2) and glucocerebroside (3) inhibited the accumulation of pro-inflammatory iNOS protein and reduced the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophages. This is the first study on the isolation of cerebrosides with anti-inflammatory activity from this TCM. PMID- 26853113 TI - Viral infection: Playing hide and seek with HIV. PMID- 26853112 TI - Single crystal functional oxides on silicon. AB - Single-crystalline thin films of complex oxides show a rich variety of functional properties such as ferroelectricity, piezoelectricity, ferro and antiferromagnetism and so on that have the potential for completely new electronic applications. Direct synthesis of such oxides on silicon remains challenging because of the fundamental crystal chemistry and mechanical incompatibility of dissimilar interfaces. Here we report integration of thin (down to one unit cell) single crystalline, complex oxide films onto silicon substrates, by epitaxial transfer at room temperature. In a field-effect transistor using a transferred lead zirconate titanate layer as the gate insulator, we demonstrate direct reversible control of the semiconductor channel charge with polarization state. These results represent the realization of long pursued but yet to be demonstrated single-crystal functional oxides on-demand on silicon. PMID- 26853114 TI - Genomes on ice. AB - This month's Genome Watch discusses the analysis of a Helicobacter pylori genome from the preserved Copper-Age mummy known as the Iceman and how ancient genomes shed light on the history of bacterial pathogens. PMID- 26853115 TI - Microbial ecology: FISHing in the oral microbiota. PMID- 26853117 TI - Bacterial evolution: How to extend your stay. PMID- 26853116 TI - Interactions of fungal pathogens with phagocytes. AB - The surveillance and elimination of fungal pathogens rely heavily on the sentinel behaviour of phagocytic cells of the innate immune system, especially macrophages and neutrophils. The efficiency by which these cells recognize, uptake and kill fungal pathogens depends on the size, shape and composition of the fungal cells and the success or failure of various fungal mechanisms of immune evasion. In this Review, we describe how fungi, particularly Candida albicans, interact with phagocytic cells and discuss the many factors that contribute to fungal immune evasion and prevent host elimination of these pathogenic microorganisms. PMID- 26853118 TI - The influence of commensal bacteria on infection with enteric viruses. AB - The intestinal microbiota exerts a marked influence in the mammalian host, both during homeostasis and disease. However, until very recently, there has been relatively little focus on the potential effect of commensal microorganisms on viral infection of the intestinal tract. In this Progress article, I review the recent advances that elucidate the mechanisms by which enteric viruses use commensal bacteria to enhance viral infectivity. These mechanisms segregate into two general categories: the direct facilitation of viral infection, including bacterial stabilization of viral particles and the facilitation of viral attachment to host target cells; and the indirect skewing of the antiviral immune response in a manner that promotes viral infection. Finally, I discuss the implications of these interactions for the development of vaccines and novel therapeutic approaches. PMID- 26853119 TI - Systematic review of the effect of intravenous lipid emulsion therapy for local anesthetic toxicity. AB - BACKGROUND: Following national and regional recommendations, intravenous lipid emulsion (ILE) has become established in clinical practice as a treatment for acute local anesthetic (LA) toxicity, although evidence of efficacy is limited to animal studies and human case reports. A collaborative lipid emulsion workgroup was therefore established by the American Academy of Clinical Toxicology to review the evidence on the effect of ILE for LA toxicity. METHODS: We performed a systematic review of the literature published through 15 December 2014. Relevant articles were determined based on pre-defined inclusion and exclusion criteria. Pre-treatment experiments, pharmacokinetic studies not involving toxicity and studies that did not address antidotal use of ILE were excluded. RESULTS: We included 113 studies and reports. Of these, 76 were human and 38 animal studies. One publication included both a human case report and an animal study. Human studies included one randomized controlled crossover trial involving 16 healthy volunteers. The subclinical LA toxicity design did not show a difference in the effects of ILE versus saline. There was one case series and 73 case reports of ILE use in the context of toxicity (83 patients) including CNS depression or agitation (n = 45, 54%), seizures (n = 49, 59%), hypotension, hypertension, EKG changes, arrhythmias (n = 39, 47%), cardiac arrest (n = 18, 22%), cardiopulmonary resuscitation, and/or requirement for endotracheal intubation and/or mechanical ventilation (n = 35, 42%). There were 81 (98%) survivors including 63 (76%) with no reported sequelae from the LA poisoning or ILE, although the presence or absence of sequelae was not reported in 15 (18%) cases. Animal studies included 29 randomized controlled studies, three observational studies, five case series, and one case report; bupivacaine was used in 29 of these reports (76%). Of 14 controlled experiments in animals, eight showed improved survival or time to return of spontaneous circulation and five no benefit of ILE versus saline or non ILE treatments. Combining ILE with epinephrine improved survival in five of the six controlled animal experiments that studied this intervention. The studies were heterogeneous in the formulations and doses of ILE used as well as the doses of LA. The body of the literature identified by this systematic review yielded only a very low quality of evidence. CONCLUSION: ILE appears to be effective for reversal of cardiovascular or neurological features in some cases of LA toxicity, but there is currently no convincing evidence showing that ILE is more effective than vasopressors or to indicate which treatment should be instituted as first line therapy in severe LA toxicity. PMID- 26853121 TI - Diastereoselective 1,3-Dipolar Cycloadditions of N,N'-Cyclic Azomethine Imines with Iminooxindoles for Access to Oxindole Spiro-N,N-bicyclic Heterocycles. AB - In the presence of CuI, 1,3-dipolar cycloadditions of N,N'-cyclic azomethine imines with iminooxindoles proceeded readily and furnished novel oxindole spiro N,N-bicyclic heterocycles in moderate to excellent chemical yields with excellent diastereoselectivities. PMID- 26853120 TI - A Common Polymorphism in a Williams Syndrome Gene Predicts Amygdala Reactivity and Extraversion in Healthy Adults. AB - BACKGROUND: Williams syndrome (WS), a genetic disorder resulting from hemizygous microdeletion of chromosome 7q11.23, has emerged as a model for identifying the genetic architecture of socioemotional behavior. Common polymorphisms in GTF2I, which is found within the WS microdeletion, have been associated with reduced social anxiety in the general population. Identifying neural phenotypes affected by these polymorphisms would help advance our understanding not only of this specific genetic association but also of the broader neurogenetic mechanisms of variability in socioemotional behavior. METHODS: Through an ongoing parent protocol, the Duke Neurogenetics Study, we measured threat-related amygdala reactivity to fearful and angry facial expressions using functional magnetic resonance imaging, assessed trait personality using the Revised NEO Personality Inventory, and imputed GTF2I rs13227433 from saliva-derived DNA using custom Illumina arrays. Participants included 808 non-Hispanic Caucasian, African American, and Asian university students. RESULTS: The GTF2I rs13227433 AA genotype, previously associated with lower social anxiety, predicted decreased threat-related amygdala reactivity. An indirect effect of GTF2I genotype on the warmth facet of extraversion was mediated by decreased threat-related amygdala reactivity in women but not men. CONCLUSIONS: A common polymorphism in the WS gene GTF2I associated with reduced social anxiety predicts decreased threat related amygdala reactivity, which mediates an association between genotype and increased warmth in women. These results are consistent with reduced threat related amygdala reactivity in WS and suggest that common variation in GTF2I contributes to broader variability in socioemotional brain function and behavior, with implications for understanding the neurogenetic bases of WS as well as social anxiety. PMID- 26853122 TI - Searching new antifungals: The use of in vitro and in vivo methods for evaluation of natural compounds. AB - In the last decades, the increased number of immunocompromised patients has led to the emergence of many forms of fungal infections. Furthermore, there are a restricted arsenal of antifungals available and an increase in the development of resistance to antifungal drugs. Because of these disadvantages, the search for new antifungal agents in natural sources has increased. The development of these new antifungal drugs involves various steps and methodologies. The evaluation of the in vitro antifungal activity and cytotoxicity are the first steps in the screening. There is also the possibility of antifungal combinations to improve the therapy and reduce toxicity. Despite that, the application of the new antifungal candidate could be used in association with photodynamic therapy or using nanotechnology as an ally. In vivo tests can be performed to evaluate the efficacy and toxicity using conventional and alternative animal models. In this work, we review the methods available for the evaluation of the antifungal activity and safety of natural products, as well as the recent advances of new technology in the application of natural products for antifungal therapy. PMID- 26853123 TI - A modified bioautographic method for antibacterial component screening against anaerobic and microaerophilic bacteria. AB - Direct bioautography is a useful method to identify antimicrobial compounds with potential therapeutic importance. Because of technical limitations till now, it has been applied only for aerobic bacteria. In this work we present the modification of the original method by which antimicrobial screening of bacteria requiring modified atmosphere became feasible by direct bioautography. Here we demonstrate its applicability by testing three anaerobic Clostridium perfringens and three microaerophilic Campylobacter jejuni strains against two essential oils, clove and thyme. Antimicrobial component profiles of clove and thyme essential oils against these two medically important pathogenic bacteria were compared and significant differences were revealed in their inhibition capacities. Linalool, a component of thyme essential oil exerted a more expressed antibacterial activity against C. perfringens than against C. jejuni. Our results demonstrate that direct bioautography is not only suitable for testing aerobic bacteria, but by applying the presently described modified version it can also contribute to the quest to find novel antimicrobial agents against multidrug resistant anaerobic and microaerophilic bacteria. PMID- 26853124 TI - Recent tuberculosis diagnosis toward the end TB strategy. AB - Tuberculosis (TB) is an infectious bacterial disease caused by Mycobacterium tuberculosis. Despite global TB eradication efforts, it is still a global public health concern, especially in low- and middle-income countries. Most of the active TB infections are curable with early diagnosis and appropriate treatment, but drug-resistant TB is difficult and expensive to treat in immunocompetent as well as immunocompromised individuals. Thus, rapid, economic, and accurate point of care tools for TB diagnosis are required urgently. This review describes the history of M. tuberculosis detection methods up to date and the recent advances using nanotechnology for point-of-care testing of TB diagnosis. PMID- 26853125 TI - Assessing the impact of long term frozen storage of faecal samples on protein concentration and protease activity. AB - BACKGROUND: The proteome is the second axis of the microbiome:host interactome and proteases are a significant aspect in this interaction. They interact with a large variety of host proteins and structures and in many situations are implicated in pathogenesis. Furthermore faecal samples are commonly collected and stored frozen so they can be analysed at a later date. So we were interested to know whether long term storage affected the integrity of proteases and total protein and whether historical native faecal samples were still a viable option for answering research questions around the functional proteome. METHODS: Faecal samples were collected from 3 healthy volunteers (3 biological replicates) and processed in order to be stored at both -20 degrees C and -80 degrees C and in a variety of storage buffers. Protein extraction, protein content and protease activity were assessed at the time of collection, after 24h, 1 week, 1 month, 3 months 6 months and finally 1 year. RESULTS: Beadbeating impacted the quantity of protein extracted, while sodium azide did not impact protease assays. Long term storage of extracted proteins showed that both total protein and protease activity were affected when they were stored as extracted protein. Intact faecal samples were shown to maintain both protein levels and protease activity regardless of time and temperature. CONCLUSIONS: Beadbeating increases the protein and protease activity when extracting from a faecal sample, however, the extracted protein is not stable and activity is lost, even with a suitable storage buffer. The most robust solution is to store the proteins in an intact frozen native faecal matrix and extract at the time of assay or analysis, this approach was shown to be suitable for samples in which, there are low levels of protease activity and which had been frozen for a year. PMID- 26853126 TI - Sublingual or subcutaneous immunotherapy for allergic rhinitis? AB - Allergen immunotherapy is effective in patients with allergic rhinitis (AR) and, unlike antiallergic drugs, has been shown to modify the underlying cause of the disease, with proved long-term benefits. Subcutaneous immunotherapy (SCIT) has been the gold standard, whereas sublingual immunotherapy (SLIT) has emerged as an effective and safe alternative. Previous Cochrane systematic reviews and meta analyses have confirmed that both SLIT and SCIT are effective in patients with seasonal AR, whereas evidence for their efficacy in patients with perennial disease has been less convincing. Recent large, adequately powered trials have demonstrated reductions in both symptoms and use of rescue medication in patients with seasonal and those with perennial AR. Here we appraise evidence for SCIT versus SLIT based on indirect evidence from Cochrane reviews and recent well powered double-blind, randomized controlled trials versus placebo and the limited direct evidence available from randomized blind head-to-head comparisons. At present, based on an overall balance of efficacy and side effects, the patient is in equipoise. Pending definitive comparative trials, choice might be determined largely by the local availability of SCIT and SLIT products of proved value and personal (patient) preference. PMID- 26853127 TI - Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: Lessons from the past and novel mechanisms of action for the future. AB - In the past, the development of more effective, safe, convenient, broadly applicable, and easy to manufacture vaccines for allergen-specific immunotherapy (AIT) has been limited by the poor quality of natural allergen extracts. Progress made in the field of molecular allergen characterization has now made it possible to produce defined vaccines for AIT and eventually for preventive allergy vaccination based on recombinant DNA technology and synthetic peptide chemistry. Here we review the characteristics of recombinant and synthetic allergy vaccines that have reached clinical evaluation and discuss how molecular vaccine approaches can make AIT more safe and effective and thus more convenient. Furthermore, we discuss how new technologies can facilitate the reproducible manufacturing of vaccines of pharmaceutical grade for inhalant, food, and venom allergens. Allergy vaccines in clinical trials based on recombinant allergens, recombinant allergen derivatives, and synthetic peptides allow us to target selectively different immune mechanisms, and certain of those show features that might make them applicable not only for therapeutic but also for prophylactic vaccination. PMID- 26853130 TI - Benign TH2 immunity in children: A fresh perspective on control of the allergic response. PMID- 26853128 TI - International Consensus on Allergen Immunotherapy II: Mechanisms, standardization, and pharmacoeconomics. AB - This article continues the comprehensive international consensus (ICON) statement on allergen immunotherapy (AIT). The initial article also recently appeared in the Journal. The conclusions below focus on key mechanisms of AIT-triggered tolerance, requirements in allergen standardization, AIT cost-effectiveness, and regulatory guidance. Potential barriers to and facilitators of the use of AIT are described in addition to future directions. International allergy specialists representing the European Academy of Allergy and Clinical Immunology; the American Academy of Allergy, Asthma & Immunology; the American College of Allergy, Asthma and Immunology; and the World Allergy Organization critically reviewed the existing literature and prepared this summary of recommendations for best AIT practice. The authors contributed equally and reached consensus on the statements presented herein. PMID- 26853131 TI - Innate mechanisms can predict successful allergy immunotherapy. PMID- 26853132 TI - pH Dependent Chiroptical Properties of (1R,2R)- and (1S,2S)-trans-Cyclohexane Diesters and Diamides from VCD, ECD, and CPL Spectroscopy. AB - Diesters of (1R,2R)- and (1S,2S)-cyclohexanediols and diamides of (1R,2R)- and (1S,2S)-diaminocyclohexane with p-hydroxycinnamic acid have been known for some time to exhibit intense bisignate electronic circular dichroism (ECD) spectra in CH3OH. It was also known that added NaOH causes a bathochromic shift of ~50 nm in CH3OH, and an even higher one in DMSO. We have measured vibrational circular dichroism (VCD) spectra both for neutral compounds and in the presence of NaOH and other bases. The VCD and IR spectra in the mid-IR region for CD3OD and DMSO d6 solution exhibit high sensitivity to the charged state for the diesters. They possess two strong bisignate features in the presence of bases in the mid-IR, which are interpreted in terms of vibrational exciton couplets, while this phenomenon is less evident in diamides. VCD allied to density functional theory (DFT) calculations allows one to shed some light on the spectral differences of diesters and diamides by studying their conformational properties. Optical rotatory dispersion (ORD) curves confirm the ECD data. Circularly polarized luminescence (CPL) data have been also acquired, which are rather intense in basified solution: the CPL spectra are monosignate and are as intense in the diester and in the diamide case. PMID- 26853133 TI - Emergency Medical Technician Training for Medical Students: A Two-Year Experience. AB - BACKGROUND: New medical school educational curriculum encourages early clinical experiences along with clinical and biomedical integration. The University of South Carolina School of Medicine Greenville, one of the new expansion schools, was established in 2011 with the first class matriculating in 2012. To promote clinical skills early in the curriculum, emergency medical technician (EMT) training was included and begins in the first semester. Along with the early clinical exposure, the program introduces interprofessional health and teams and provides the opportunity for students to personally see and appreciate the wide variety of environments from which their future patients emanate. OBJECTIVE: This report describes the EMT program and changes that were made after the first class that were designed to integrate EMT training with the biomedical sciences and to assess the value of these integrative changes using objective criteria. METHODS: A two-year retrospective study was conducted that involved the first two classes of medical students. Baseline student data and pass rates from the psychomotor skill and written components of the State examination were used to determine if students performed better in the integrated, prolonged course. RESULTS: There were 53 students in the first class and 54 in the second. Of the 51 students in the first class and 53 students in the second class completing the state psychomotor and written examination, 20 (39%) in the first class and 17 (32%) in the second passed on the initial psychomotor skill attempt; however, more students passed in the first three attempts in the second class than the first class, 51 (96%) versus 45 (88%) , respectively. All students passed by 5 attempts. For the written examination, 50 (98%) students in the first class and 51 (96%) in the second class passed on the first attempt. All students passed by the third attempt. Pass rates on both components of the State examination were not significantly different between classes. CONCLUSION: Medical students who received their EMT training in a 6-week, non-integrated format performed similarly on the EMT State certification examination to those who received their training in a prolonged, integrated structure. PMID- 26853134 TI - Human cytomegalovirus infection and the immune response to exercise. AB - Human cytomegalovirus (HCMV) is a ubiquitous -herpes virus that has co-evolved with its host since the very beginning of human life. The vast majority of adults worldwide carry the virus in a latent state, which is known to have striking effects on the composition and function of both T-cells and NK-cells. While there is evidence to suggest that prior exposure to HCMV can have beneficial effects in the immune competent host, poor control of the virus may contribute to T-cell exhaustion and the early onset of immunosenescence. The interaction between HCMV and exercise has garnered a lot of recent research attention. This stemmed from observations that people with HCMV redeploy greater numbers of CD8+ T-cells in response to a single exercise bout, while NK-cell mobilization is, conversely, impaired. Moreover, athletes with latent HCMV infection may be better protected against symptoms of upper respiratory illness (URI), and it has been suggested that the host's ability to control HCMV (i.e. keeping CMV in a latent state) may connect apparent bidirectional effects of exercise volume on host immunity and infection risk. This work has set a new paradigm that immune responses to both acute and chronic exercise might be governed by the infection history of the host. In this review, we summarize current knowledge on the effects of HCMV infection on T-cells and NK-cells and synthesize the literature on HCMV and the immune response to both single exercise bouts and prolonged periods of exercise training. We also discuss potential clinical and practical applications of this work including the use of HCMV reactivation as a biomarker of immune depression in athletes, its relevance in immunosenescence and the associated immune risk profile, and the potential for exercise to augment vaccine responses and the man ufacture of immune cells for adoptive transfer immunotherapy. Although research in this area is still in its infancy, we conclude that host infection history and the ability to regulate dormant pathogens is likely to play a key role in our understanding of how the immune system responds to both acute and chronic exercise across the entire exercise volume continuum. PMID- 26853135 TI - Bispecific Antibodies for Targeted Delivery of Dendritic Polyglycerol (dPG) Prodrug Conjugates. AB - One approach to further improve the therapeutic efficacy of nanoparticles is employment of active targeting strategies. Bispecific antibodies (bsAbs) that bind to both tumor specific antigens on the cell surface and to haptens such as digoxigenin (Dig) can direct digoxigeninylated payloads to tumor cells. In this study, we investigate the potential of dendritic polyglycerol (dPG) conjugates, which consist of a doxorubicin (DOX) prodrug, Dig moiety, and a poly (ethylene glycol) (PEG) shell, in combination with bsAb, as a novel approach for targeted prodrug delivery. We could show successful binding of the bsAbs to dPGDigMal- DOX PEG conjugates, as well as binding of these complexes to the cell surface of Lewis Y (LeY) expressing MCF-7 cells. Using flow cytometry, we could show the preferential binding of the targeting complex over the complex of control conjugate lacking Dig moieties. At concentrations that are usually applied for drug delivery, antibodycomplexed nanoparticles (independent of antibody specificity) released cytotoxic compounds into cells to the same degree as unmodified nanoparticles. This indicates that antibody-attachment does not interfere with the inherent cell binding and drug delivery properties of nanoparticles. At low doxorubicin concentrations and short incubation times, however, we were able to see a slightly increased target specific cytotoxicity in vitro which is mediated by complexation of the digoxigeninylated NP with the Dig binding moiety of a bsAb that in turns direct the complexed bsAb to target cells. This study demonstrates the potential of digoxigeninylated dPG prodrug conjugates in combination with bsAbs as a new platform for targeted prodrug delivery into cancerous tissues. However the nanoparticle design needs to be further optimized for significant targeted delivery. PMID- 26853136 TI - Abnormal response of distal Schwann cells to denervation in a mouse model of motor neuron disease. AB - In several animal models of motor neuron disease, degeneration begins in the periphery. Clarifying the possible role of Schwann cells remains a priority. We recently showed that terminal Schwann cells (TSCs) exhibit abnormalities in postnatal mice that express mutations of the SOD1 enzyme found in inherited human motor neuron disease. TSC abnormalities appeared before disease-related denervation commenced and the extent of TSC abnormality at P30 correlated with the extent of subsequent denervation. Denervated neuromuscular junctions (NMJs) were also observed that lacked any labeling for TSCs. This suggested that SOD1 TSCs may respond differently than wildtype TSCs to denervation which remain at denervated NMJs for several months. In the present study, the response of SOD1 TSCs to experimental denervation was examined. At P30 and P60, SC-specific S100 labeling was quickly lost from SOD1 NMJs and from preterminal regions. Evidence indicates that this loss eventually becomes complete at most SOD1 NMJs before reinnervation occurs. The loss of labeling was not specific for S100 and did not depend on loss of activity. Although some post-denervation labeling loss occurred at wildtype NMJs, this loss was never complete. Soon after denervation, large cells appeared near SOD1 NMJ bands which colabeled for SC markers as well as for activated caspase-3 suggesting that distal SOD1 SCs may experience cell death following denervation. Denervated SOD1 NMJs viewed 7 days after denervation with the electron microscope confirmed the absence of TSCs overlying endplates. These observations demonstrate that SOD1 TSCs and distal SCs respond abnormally to denervation. This behavior can be expected to hinder reinnervation and raises further questions concerning the ability of SOD1 TSCs to support normal functioning of motor terminals. PMID- 26853138 TI - Carotid Intima-Media Thickness is Not Associated with Markers of Atherosclerosis in Stroke Patients. AB - BACKGROUND: It has been argued that carotid intima-media thickness (IMT) could better reflect an adaptive response of the vessel wall rather than being a marker of atherosclerosis. We explore this hypothesis by analyzing the ARTICO data. METHODS: The ARTICO study was designed to evaluate the prognostic value of the pathological ankle-brachial index (ABI) for the emergence of new vascular events in patients who have suffered a noncardioembolic stroke. Collected variables were as follows: vascular risk factors, mean waist perimeter, quantification of carotid IMT, characteristics of carotid plaques, ABI, and presence of microalbuminuria. RESULTS: A total of 591 patients with a complete carotid evaluation were available. There was no correlation between ABI and IMT (Spearman's, p NS). Logistic regression revealed that pathological ABI correlated significantly only with internal carotid artery stenosis greater than or equal to 50% (OR [odds ratio] 2.80, 1.66-4.71, P < .01) and peripheral artery disease (OR 3.33, 1.63-6.78, P < .01). However, multivariate regression analysis demonstrated that carotid IMT was independently associated with age (OR 1.05, 95% confidence interval [CI] 1.02-1.09, P < .01), hypertension (OR 1.83, 95% CI 1.02-3.26, P = .04), waist circumference (OR 1.03, 95% CI 1.01-1.05, P < .01), and microalbuminuria (OR 2.02, 95% CI 1.22-3.35, P < .01). CONCLUSION: In our patients, carotid IMT does not seem to be associated with unequivocal markers of atheromatosis such as the existence of relevant carotid plaques or pathological ABI. These results as well as the association of IMT with age, hypertension, microalbuminuria, and mean waist perimeter support the hypothesis that IMT must be considered a risk factor for general vascular disease rather than a marker of atherosclerotic burden. PMID- 26853137 TI - Continuing versus Stopping Prestroke Antihypertensive Therapy in Acute Intracerebral Hemorrhage: A Subgroup Analysis of the Efficacy of Nitric Oxide in Stroke Trial. AB - BACKGROUND AND PURPOSE: More than 50% of patients with acute intracerebral hemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. METHODS: ENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood, cognition, and quality of life. RESULTS: Blood pressure level (baseline 171/92 mmHg) fell in both groups but was significantly lower at 7 days in those patients assigned to continue antihypertensive drugs (difference 9.4/3.5 mmHg, P < .01). At 90 days, the primary outcome did not differ between the groups; the adjusted common odds ratio (OR) for worse outcome with continue versus stop drugs was .92 (95% confidence interval, .45-1.89; P = .83). There was no difference between the treatment groups for any secondary outcome measure, or rates of death or serious adverse events. CONCLUSIONS: Among patients with acute ICH, immediate continuation of antihypertensive drugs during the first week did not reduce death or major disability in comparison to stopping treatment temporarily. PMID- 26853139 TI - Analyses of the Turkish National Intravenous Thrombolysis Registry. AB - BACKGROUND: The relatively late approval of use of recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke in Turkey has resulted in obvious underuse of this treatment. Here we present the analyses of the nationwide registry, which was created to prompt wider use of intravenous thrombolysis, as well as to monitor safe implementation of the treatment in our country. METHODS: Patients were registered prospectively in our database between 2006 and 2013. Admission and 24-hour National Institutes of Health Stroke Scale and 3-month modified Rankin Scale scores were recorded. A "high-volume center" was defined as a center treating 10 or more patients with rt-PA per year. RESULTS: A total of 1133 patients were enrolled into the registry by 38 centers in 18 cities. A nearly 4-fold increase in the study population and in the number of participating centers was observed over the 6 years of the study. The mean baseline NIHSS score was 14.5 +/- 5.7, and the prevalence of symptomatic hemorrhage was 4.9%. Mortality at 3 months decreased from 22% to 11% in the 6 years of enrollment, and 65% of cases were functionally independent. Age older than 70 years, an NIHSS score higher than 14 upon hospital admission, and intracranial hemorrhage were independently associated with mortality, and being treated in a high-volume center was related to good outcome. CONCLUSIONS: We observed a decreasing trend in mortality and an acceptable prevalence of symptomatic hemorrhage over 6 years with continuous addition of new centers to the registry. The first results of this prospective study are encouraging and will stimulate our efforts at increasing the use of intravenous thrombolysis in Turkey. PMID- 26853140 TI - The D9N, N291S, and T495G Polymorphisms of the Lipoprotein Lipase Gene Are Not Associated with Cerebral Infarction. AB - BACKGROUND: Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism and its polymorphisms are possibly implicated in the etiology of ischemic cerebrovascular disease (CVD). The aim of this work was to determine the association of the of D9N, N291S, and T495G polymorphisms of the LPL gene as a risk factor for the development of CVD. METHODS: A case-control study was conducted that included 100 patients with CVD and 120 healthy controls. All the subjects were genotyped for the D9N, N291S, and T495G polymorphisms of the LPL gene through polymerase chain reaction-restriction fragment length polymorphism, and the results were analyzed for their association with CVD. RESULTS: The D9N genotype was not significantly correlated with CVD; the odds ratio (OR) between the control subjects and CVD patients was .29 (95% confidence interval [CI], .03-2.66; P = .27). The N291S polymorphism was not significantly correlated with CVD either; the OR between the control subjects and CVD patients was 1.2 (95% CI, .07-19.46; P = .89). And the T495G mutation was not significantly correlated with CVD; the OR between the control subjects and the CVD patients was 1.21 (95% CI, .7-2.08; P = .48). CONCLUSIONS: In the present study, the D9N, N291S, and T495G polymorphisms of the LPL gene were not risk factors for the development of CVD. PMID- 26853141 TI - Stroke and Heart Failure: Clinical Features, Access to Care, and Outcomes. AB - BACKGROUND AND OBJECTIVES: Limited information is known regarding acute ischemic stroke (AIS) and heart failure (HF). The aim of the study was to evaluate clinical characteristics, predisposing factors, and outcomes in AIS with HF. METHODS: We included AIS patients admitted to the institutions participating in the Registry of the Canadian Stroke Network. HF was defined as history of pre existing HF or pulmonary edema present at the time of arrival. The primary outcome was death or disability at discharge (modified Rankin Scale score >3). Secondary outcomes included disposition, death at 3 months and at 1 year, and 30 day hospital readmissions. RESULTS: Among 12,396 patients, HF was found in 1124 (9.1%) patients. HF was associated with higher risk of death at 30 days (24.5% versus 11.2%, P < .0001), at 1 year (44.3% versus 20.6, P < .0001), and disability at discharge (70.4% versus 56%, P < .0001). In the multivariable analysis, HF was an independent predictor of death and disability (odds ratio 1.18, 95% confidence interval [CI] 1.01-1.37), death at 30 days (hazard ratio [HR] 1.22, 95% CI 1.05-1.41), and hospital readmissions (HR 1.32, 95% CI 1.05 1.65) at 30 days. The results were unaltered when adjusting for pneumonia with the exception of death or disability at discharge. CONCLUSIONS: In this large cohort study, HF was observed in 9.1% of AIS patients. HF is an independent predictor of death and disability and hospital readmissions after stroke at 30 days. PMID- 26853142 TI - Proton Pump Inhibitors versus Histamine-2 Receptor Antagonists and Risk of Pneumonia in Patients with Acute Stroke. AB - BACKGROUND: Pneumonia is a serious complication of stroke. Several studies have indicated that certain gastric acid suppressants may be associated with an increased risk of pneumonia in hospitalized patients. However, the association between type of acid suppressant and pneumonia in acute stroke patients remains controversial. The purpose of this study was to clarify the association between the type of acid suppressant and the occurrence of pneumonia in acute stroke patients. METHODS: This retrospective observational study used data from the national Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted to acute-care hospitals with stroke. The outcome was the occurrence of pneumonia assessed using diagnostic codes. We performed propensity score-matched analysis to compare the outcome between proton pump inhibitor (PPI) users and histamine-2 receptor antagonist (H2RA) users. RESULTS: A total of 77,890 stroke patients were identified, of whom 63,980 were prescribed H2RAs and 13,910 were prescribed PPIs. Overall, 1490 (10.7%) of the patients receiving PPIs and 6401 (10.0%) of the patients receiving H2RAs developed pneumonia after stroke. After propensity score matching, the incidence of pneumonia in PPI users was not different from that in H2RA users (odds ratio: 1.10, 95% confidence interval: .99-1.21). CONCLUSION: No significant difference in the incidence of pneumonia was seen between users of PPIs and H2RAs after acute stroke. PMID- 26853143 TI - Door to Intravenous Tissue Plasminogen Activator Time and Hospital Length of Stay in Acute Ischemic Stroke Patients, Georgia, 2007-2013. AB - BACKGROUND: Ischemic stroke patients benefit most from intravenous thrombolysis when they receive the treatment as quickly as possible after symptom onset. Hospitals participating in the Georgia Coverdell Acute Stroke Registry reduced the time from patient arrival to administration of intravenous tissue plasminogen activator. This study evaluates the benefit of reducing door-to-treatment (DTT) time as measured by hospital length of stay (LOS). METHODS: Data from 3154 ischemic stroke patients treated with intravenous thrombolysis from 2007 to 2013 were analyzed. The impact of door-to-treatment time on patients' length of hospital stay, discharge disposition, ambulatory status at discharge, and bleeding complications was assessed, controlling for patient-, hospital- and event-related characteristics. RESULTS: Patients who received intravenous thrombolysis within 30 minutes of hospital arrival had a 19% shorter (95% confidence interval [CI]: 2%-32%, P value = .04) hospital LOS than those treated for more than 120 minutes after arrival. Patients treated within 60 minutes of arrival were 27% more likely (odds ratio = 1.28, 95% CI: 1.06-1.56, P = .01) to have a better discharge disposition than patients treated after 60 minutes of arrival while having a similar rate of bleeding complications. CONCLUSIONS: Shortening the door-to-treatment time is associated with a decrease in patient LOS and better patient outcomes. Hospitals should be encouraged to measure, monitor, and reduce DTT time progressively for a better patient outcome. PMID- 26853144 TI - Stroke in Young-Dilative Arteriopathy: A Clue to Late-Onset Pompe's Disease? AB - IMPORTANCE: In almost a third of stroke in young cases, etiology remains unclear. We report a radiological entity which might give a clue toward detection of late onset Pompe's disease in some cases. OBSERVATION: Here we report two cases of stroke in young in which evaluation led to diagnosis of late onset Pompe's disease. Both patients presented with recurrent stroke. On evaluation, one of them was found to have slowly progressive predominantly proximal quadriparesis. His muscle biopsy showed Pompe's disease and had dolichoectasia of posterior circulation vessels. The other patient did not have any muscle weakness. Detailed workup for stroke in young was negative, but as angiogram showed intracranial vessel dolichoectasia, he was also investigated and found to have Pompe's disease. CONCLUSIONS AND RELEVANCE: We conclude that dolichoectasia of intracranial vessels in cases with stroke in young, with or without muscle weakness, should raise a differential of late onset Pompe's disease. This being one of the few treatable disorders makes the diagnosis all the more important. PMID- 26853145 TI - Sequential Engagement of Distinct MLKL Phosphatidylinositol-Binding Sites Executes Necroptosis. AB - Necroptosis is a cell death pathway regulated by the receptor interacting protein kinase 3 (RIPK3) and the mixed lineage kinase domain-like (MLKL) pseudokinase. How MLKL executes plasma membrane rupture upon phosphorylation by RIPK3 remains controversial. Here, we characterize the hierarchical transduction of structural changes in MLKL that culminate in necroptosis. The MLKL brace, proximal to the N terminal helix bundle (NB), is involved in oligomerization to facilitate plasma membrane targeting through the low-affinity binding of NB to phosphorylated inositol polar head groups of phosphatidylinositol phosphate (PIP) phospholipids. At the membrane, the NB undergoes a "rolling over" mechanism to expose additional higher-affinity PIP-binding sites responsible for robust association to the membrane and displacement of the brace from the NB. PI(4,5)P2 is the preferred PIP-binding partner. We investigate the specific association of MLKL with PIPs and subsequent structural changes during necroptosis. PMID- 26853148 TI - Global Hib vaccination: reasons to cheer and fear. PMID- 26853150 TI - A new Associate Editor for Drug and Alcohol Dependence: Dr. Adam Leventhal. PMID- 26853147 TI - Structural Basis and Functional Role of Intramembrane Trimerization of the Fas/CD95 Death Receptor. AB - Fas (CD95, Apo-1, or TNFRSF6) is a prototypical apoptosis-inducing death receptor in the tumor necrosis factor receptor (TNFR) superfamily. While the extracellular domains of TNFRs form trimeric complexes with their ligands and the intracellular domains engage in higher-order oligomerization, the role of the transmembrane (TM) domains is unknown. We determined the NMR structures of mouse and human Fas TM domains in bicelles that mimic lipid bilayers. Surprisingly, these domains use proline motifs to create optimal packing in homotrimer assembly distinct from classical trimeric coiled-coils in solution. Cancer-associated and structure based mutations in Fas TM disrupt trimerization in vitro and reduce apoptosis induction in vivo, indicating the essential role of intramembrane trimerization in receptor activity. Our data suggest that the structures represent the signaling-active conformation of Fas TM, which appears to be different from the pre-ligand conformation. Analysis of other TNFR sequences suggests proline containing sequences as common motifs for receptor TM trimerization. PMID- 26853149 TI - Effect of Haemophilus influenzae type b vaccination without a booster dose on invasive H influenzae type b disease, nasopharyngeal carriage, and population immunity in Kilifi, Kenya: a 15-year regional surveillance study. AB - BACKGROUND: Haemophilus influenzae type b (Hib) conjugate vaccine, delivered as a three-dose series without a booster, was introduced into the childhood vaccination programme in Kenya in 2001. The duration of protection and need for a booster dose are unknown. We aimed to assess vaccine effectiveness, the impact of the vaccine on nasopharyngeal carriage, and population immunity after introduction of conjugate Hib vaccine in infancy without a booster dose in Kenya. METHODS: This study took place in the Kilifi Health and Demographic Surveillance System (KHDSS), an area of Kenya that has been monitored for vital events and migration every 4 months since 2000. We analysed sterile site cultures for H influenzae type b from children (aged <=12 years) admitted to the Kilifi County Hospital (KCH) from Jan 1, 2000, through to Dec 31, 2014. We determined the prevalence of nasopharyngeal carriage by undertaking cross-sectional surveys in random samples of KHDSS residents (of all ages) once every year from 2009 to 2012, and measured Hib antibody concentrations in five cross-sectional samples of children (aged <=12 years) within the KHDSS (in 1998, 2000, 2004-05, 2007, and 2009). We calculated incidence rate ratios between the prevaccine era (2000-01) and the routine-use era (2004-14) and defined vaccine effectiveness as 1 minus the incidence rate ratio, expressed as a percentage. FINDINGS: 40,482 children younger than 13 years resident in KHDSS were admitted to KCH between 2000 and 2014, 38,206 (94%) of whom had their blood cultured. The incidence of invasive H influenzae type b disease in children younger than 5 years declined from 62.6 (95% CI 46.0-83.3) per 100,000 in 2000-01 to 4.5 (2.5-7.5) per 100,000 in 2004 14, giving a vaccine effectiveness of 93% (95% CI 87-96). In the final 5 years of observation (2010-14), only one case of invasive H influenzae type b disease was detected in a child younger than 5 years. Nasopharyngeal H influenzae type b carriage was detected in one (0.2%) of 623 children younger than 5 years between 2009 and 2012. In the 2009 serosurvey, 92 (79%; 95% CI 70-86) of 117 children aged 4-35 months had long-term protective antibody concentrations. INTERPRETATION: In this region of Kenya, use of a three-dose primary series of Hib vaccine without a booster dose has resulted in a significant and sustained reduction in invasive H influenzae type b disease. The prevalence of nasopharyngeal carriage is low and the profile of Hib antibodies suggests that protection wanes only after the age at greatest risk of disease. Although continued surveillance is important to determine whether effective control persists, these findings suggest that a booster dose is not currently required in Kenya. FUNDING: Gavi, the Vaccine Alliance, Wellcome Trust, European Society for Paediatric Infectious Diseases, and National Institute for Health Research. PMID- 26853146 TI - Allele-Specific Reprogramming of Cancer Metabolism by the Long Non-coding RNA CCAT2. AB - Altered energy metabolism is a cancer hallmark as malignant cells tailor their metabolic pathways to meet their energy requirements. Glucose and glutamine are the major nutrients that fuel cellular metabolism, and the pathways utilizing these nutrients are often altered in cancer. Here, we show that the long ncRNA CCAT2, located at the 8q24 amplicon on cancer risk-associated rs6983267 SNP, regulates cancer metabolism in vitro and in vivo in an allele-specific manner by binding the Cleavage Factor I (CFIm) complex with distinct affinities for the two subunits (CFIm25 and CFIm68). The CCAT2 interaction with the CFIm complex fine tunes the alternative splicing of Glutaminase (GLS) by selecting the poly(A) site in intron 14 of the precursor mRNA. These findings uncover a complex, allele specific regulatory mechanism of cancer metabolism orchestrated by the two alleles of a long ncRNA. PMID- 26853151 TI - Cognition and impulsivity in adults with attention deficit hyperactivity disorder with and without cocaine and/or crack dependence. AB - BACKGROUND: Substance use disorder (SUD) is a common comorbidity in adults with attention deficit-hyperactivity disorder (ADHD). However,there have been few studies on cognitive profiles of these patients. Impulsivity is also commonly increased in both disorders. The central aim of this study was to compare cognition and impulsivity in subjects who had ADHD and cocaine dependence (ADHD+COC group) to those with ADHD only (ADHD-noSUD group). We hypothesized that the ADHD+COC group would show more marked cognitive dysfunction and greater impulsivity than their counterparts with ADHD only. METHODS: A total of 70 adult patients diagnosed with ADHD according to (DSM-IV-TR) criteria were enrolled; 36 with ADHD+COC and 34 with ADHD-noSUD. All study participants were evaluated with a sociodemographic questionnaire; the Mini International Neuropsychiatric Interview; the Adult ADHD Self-Report Scale; the Addiction Severity Index; the Alcohol, Smoking and Substance Involvement Screening Test; the Barratt Impulsiveness Scale; and a comprehensive neurocognitive battery. RESULTS: Compared to individuals with ADHD-noSUD, ADHD+COC individuals had significantly lower mean IQ and higher motor impulsivity. On average, the ADHD+COC group also performed more poorly on tasks assessing verbal skills, vigilance, implicit learning during decision making, and ADHD-noSUD performed more poorly on selective attention, information processing, and visual search. CONCLUSIONS: Our results support the integrative theory of ADHD based on the cognitive and affective neuroscience model, and suggests that ADHD-noSUD patients have impairments in cognitive regulation, while ADHD+COC patients have impairments in both cognitive and affective regulation. PMID- 26853154 TI - Superior high-rate capability of Na3(VO(0.5))2(PO4)2F2 nanoparticles embedded in porous graphene through the pseudocapacitive effect. AB - Na3(VO(0.5))2(PO4)2F2 nanoparticles embedded in porous graphene have been reported as a superior high-rate cathode material for sodium-ion batteries, exhibiting an excellent electrochemical performance with a high reversible capacity of 100 mA h g(-1) at 1 C, 77 mA h g(-1) at 50 C, and a capacity retention of 73% after 1000 cycles at 50 C. In particular, a significant contribution of the pseudocapacitive effect to the Na-storage capacity has been found for the first time. PMID- 26853152 TI - Chlordecone potentiates hepatic fibrosis in chronic liver injury induced by carbon tetrachloride in mice. AB - Chronic liver damage due to viral or chemical agents leads to a repair process resulting in hepatic fibrosis. Fibrosis may lead to cirrhosis, which may progress to liver cancer or a loss of liver function, with an associated risk of liver failure and death. Chlordecone is a chlorinated pesticide used in the 1990s. It is not itself hepatotoxic, but its metabolism in the liver triggers hepatomegaly and potentiates hepatotoxic agents. Chlordecone is now banned, but it persists in soil and water, resulting in an ongoing public health problem in the Caribbean area. We assessed the probable impact of chlordecone on the progression of liver fibrosis in the population of contaminated areas, by developing a mouse model of chronic co-exposure to chlordecone and a hepatotoxic agent, carbon tetrachloride (CCl4). After repeated administrations of chlordecone and CCl4 by gavage over a 12-week period, we checked for liver damage in the exposed mice, by determining serum liver transaminase (AST, ALT) levels, histological examinations of the liver and measuring the expression of genes encoding extracellular matrix components. The co-exposure of mice to CCl4 and chlordecone resulted in significant increases in ALT and AST levels. Chlordecone also increased expression of the Col1A2, MMP-2, TIMP-1 and PAI-1 genes in CCl4-treated mice. Finally, we demonstrated, by quantifying areas of collagen deposition and alpha SMA gene expression, that chlordecone potentiated the hepatic fibrosis induced by CCl4. In conclusion, our data suggest that chlordecone potentiates hepatic fibrosis in mice with CCl4-induced chronic liver injury. PMID- 26853153 TI - Differential gene expression pattern in human mammary epithelial cells induced by realistic organochlorine mixtures described in healthy women and in women diagnosed with breast cancer. AB - Organochlorine pesticides (OCs) have been associated with breast cancer development and progression, but the mechanisms underlying this phenomenon are not well known. In this work, we evaluated the effects exerted on normal human mammary epithelial cells (HMEC) by the OC mixtures most frequently detected in healthy women (H-mixture) and in women diagnosed with breast cancer (BC-mixture), as identified in a previous case-control study developed in Spain. Cytotoxicity and gene expression profile of human kinases (n=68) and non-kinases (n=26) were tested at concentrations similar to those described in the serum of those cases and controls. Although both mixtures caused a down-regulation of genes involved in the ATP binding process, our results clearly indicate that both mixtures may exert a very different effect on the gene expression profile of HMEC. Thus, while BC-mixture up-regulated the expression of oncogenes associated to breast cancer (GFRA1 and BHLHB8), the H-mixture down-regulated the expression of tumor suppressor genes (EPHA4 and EPHB2). Our results indicate that the composition of the OC mixture could play a role in the initiation processes of breast cancer. In addition, the present results suggest that subtle changes in the composition and levels of pollutants involved in environmentally relevant mixtures might induce very different biological effects, which explain, at least partially, why some mixtures seem to be more carcinogenic than others. Nonetheless, our findings confirm that environmentally relevant pollutants may modulate the expression of genes closely related to carcinogenic processes in the breast, reinforcing the role exerted by environment in the regulation of genes involved in breast carcinogenesis. PMID- 26853156 TI - Pregnane steroids from a gorgonian coral Subergorgia suberosa with anti-flu virus effects. AB - Five new pregnane-type steroids namely subergorgols T-X (1-5) and three known analogues (6-8) were isolated from a gorgonian coral Subergorgia suberosa. The structures of new compounds were determined on the basis of extensive spectroscopic (IR, MS, 1D and 2D NMR) data analyses, in association with photochemical transformation and ECD methods for the configurational assignment. Compounds 1-8 were evaluated for the inhibitory effects against H1N1 virus infected in MDCK cells, while subergorgols T-U and 1,2-dehydroprogesterone exerted potent inhibition against A/WSN/33 virus. PMID- 26853155 TI - Effects of individually silenced N-glycosylation sites and non-synonymous single nucleotide polymorphisms on the fusogenic function of human syncytin-2. AB - The placental syncytiotrophoblast, which is formed by the fusion of cytotrophoblast cells, is indispensable for the establishment and maintenance of normal pregnancy. The human endogenous retrovirus envelope glycoprotein syncytin 2 is the most important player in mediating trophoblast cell-cell fusion as a fusogen. We constructed expression plasmids of wild-type and 21 single-amino-acid substitution mutants of syncytin-2, including 10 N-glycosylation sites individually silenced by mutagenizing N to Q, 1 naturally occurring single nucleotide polymorphism (SNP) N118S that introduced an N-glycosylation site, and another 10 non-synonymous SNPs located within important functional domains. We observed that syncytin-2 was highly fusogenic and that the mutants had different capacities in merging 293T cells. Of the 21 mutants, N133Q, N312Q, N443Q, C46R (in the CXXC motif) and R417H (in the heptad repeat region and immunosuppressive domain) lost their fusogenicity, whereas N332Q, N118S, T367M (in the fusion peptide), V483I (in the transmembrane domain) and T522M (in the cytoplasmic domain) enhanced the fusogenic activity. We also proved that N133, N146, N177, N220, N241, N247, N312, N332 and N443 were all glycosylated in 293T cells. A co immunoprecipitation assay showed compromised interaction between mutants N443Q, C46R, T367M, R417H and the receptor MFSD2A, whereas N118S was associated with more receptors. We also sequenced the coding sequence of syncytin-2 in 125 severe pre-eclamptic patients and 272 normal pregnant Chinese women. Surprisingly, only 1 non-synonymous SNP T522M was found and the frequencies of heterozygous carriers were not significantly different. Taken together, our results suggest that N glycans at residues 133, 312, 332 and 443 of syncytin-2 are required for optimal fusion induction, and that SNPs C46R, N118S, T367M, R417H, V483I and T522M can alter the fusogenic function of syncytin-2. PMID- 26853157 TI - Atypical excretion profile and GC/C/IRMS findings may last for nine months after a single dose of nandrolone decanoate. AB - The use of the anabolic androgenic steroid nandrolone and its prohormones is prohibited in sport. A common route of nandrolone administration is intramuscular injections of a nandrolone ester. Here we have investigated the detection time of nandrolone and 19-norandrosterone and 19-noretiocholanolone metabolites in eleven healthy men after the administration of a 150 mg dose of nandrolone decanoate. The urinary concentrations of nandrolone and the metabolites were monitored by GC MS/MS for nine months and in some samples the presence of 19-norandrosterone was confirmed by GC/C/IRMS analysis. The participants were genotyped for polymorphisms in PDE7B1 and UGT2B15 genes previously shown to influence the activation and inactivation of nandrolone decanoate. There were large inter individual variations in the excretion rate of nandrolone and the metabolites, although not related to genetic variations in the UGT2B15 (rs1902023) and PDE7B1 (rs7774640) genes. After the administration, 19-norandrosterone was found at 2-8 fold higher concentrations than 19-noretiocholanolone. We showed that nandrolone doping can be identified 4 and 9 months after the injection of only one single dose in six and three individuals, respectively. We also noted that GC/C/IRMS confirms the presence of exogenous 19-norandrosterone in the urine samples, showing delta13 values around -32 0/00. This was true even in a sample that was not identified as an atypical finding after the GC-MS/MS analysis further showing the power of using GC/C/IRMS in routine anti-doping settings. PMID- 26853158 TI - Targeting arachidonic acid pathway by natural products for cancer prevention and therapy. AB - Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A2s (PLA2s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6] gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA2s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. PMID- 26853159 TI - Reply. PMID- 26853160 TI - Reply. PMID- 26853161 TI - Reply. PMID- 26853162 TI - Reply. PMID- 26853163 TI - Graphene Folding in Si Rich Carbon Nanofibers for Highly Stable, High Capacity Li Ion Battery Anodes. AB - Silicon nanoparticles (Si NPs) wrapped by graphene in carbon nanofibers were obtained via electrospinning and subsequent thermal treatment. In this study, water-soluble poly(vinyl alcohol) (PVA) with low carbon yield is selected to make the process water-based and to achieve a high silicon yield in the composite. It was also found that increasing the amount of graphene helps keep the PVA fiber morphology after carbonization, while forming a graphene network. The fiber SEM and HRTEM images reveal that micrometer graphene is heavily folded into sub micron scale fibers during electrospinning, while Si NPs are incorporated into the folds with nanospace in between. When applied to lithium-ion battery anodes, the Si/graphene/carbon nanofiber composites show a high reversible capacity of ~2300 mAh g(-1) at a charging rate of 100 mA/g and a stable capacity of 1191 mAh g(-1) at 1 A/g after more than 200 cycles. The interconnected graphene network not only ensures the excellent conductivity but also serves as a buffering matrix for the mechanic stress caused by volume change; the nanospace between Si NPs and folded graphene provides the space needed for volume expansion. PMID- 26853167 TI - Anion inhibition studies of the beta-carbonic anhydrase from the pathogenic bacterium Vibrio cholerae. AB - The genome of the pathogenic bacterium Vibrio cholerae encodes for three carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the alpha-, beta- and gamma-classes. Here we report and anion inhibition study of the beta-CA, VchCAbeta with anions and other small molecules which inhibit metalloenzymes. The best VchCAbeta anion inhibitors were sulfamide, sulfamate, phenylboronic acid and phenylarsonic acid, which showed KIs in the range of 54-86MUM. Diethyldithiocarbonate was also an effective VchCAbeta inhibitor, with an inhibition constant of 0.73mM. The halides, cyanate, thiocyanate, cyanide, bicarbonate, carbonate, nitrate, nitrite, stannate, selenate, tellurate, divanadate, tetraborate, perrhenate, perruthenate, peroxydisulfate, selenocyanide, trithiocarbonate, and fluorosulfonate showed affinity in the low millimolar range, with KIs of 2.3-9.5mM. Identification of selective inhibitors of VchCAbeta (over the human CA isoforms) may lead to pharmacological tools useful for understanding the physiological role(s) of this under-investigated enzyme. PMID- 26853168 TI - Gonadotropins facilitate potential differentiation of human bone marrow mesenchymal stem cells into Leydig cells in vitro. AB - Infertility due to low testosterone levels has increased in recent years. This has impacted the social well-being of the patients. This study was undertaken to investigate the potential of gonadotropins in facilitating differentiation of human bone marrow mesenchymal stem cells (BMSCs) into Leydig cells in vitro. BMSCs were isolated, cultured, and their biological characteristics were observed. BMSCs were induced with gonadotropins in vitro and their ability to differentiate into Leydig cells was studied. The level of expression of 3-beta hydroxysteroid dehydrogenase (3beta-HSD) and secretion of testosterone were determined using flow cytometry and enzyme-linked immunosorbent assay, respectively, and the results were compared between the experimental and control groups. The cultured BMSCs showed a typical morphology of the fibroblast-like colony. The growth curve of cells formed an S-shape. After inducing the cells for 8-13 days, the cells in the experimental group increased in size and showed typical characteristics of Leydig cells, and the growth occurred in spindle or stellate shapes. Cells from the experimental group highly expressed 3beta-HSD, and there was a gradual increase in the number of Leydig cells. The control group did not express 3beta-HSD. The level of testosterone in the experimental group was higher than the control group (p < 0.05). Additionally, the cells in the experimental group secreted higher levels of testosterone with increased culture time. The expression of Leydig cell-specific markers in the experimental group was significantly higher (p < 0.05). With these findings, BMSCs can be considered a new approach for the treatment of patients with low androgen levels. PMID- 26853171 TI - Safety and efficacy of panretinal photocoagulation in patients with high-risk proliferative diabetic retinopathy using pattern scan laser versus conventional YAG laser. AB - The purpose of the study was to compare the results of panretinal photocoagulation (PRP) using the pattern scan laser (PASCAL) in a single setting versus multiple sessions of standard YAG laser in patients with proliferative diabetic retinopathy. Charts of 35 eyes that were treated with the PASCAL and an equal number of eyes that were treated with conventional laser were retrospectively reviewed. The whole PRP treatment was performed in one session in the PASCAL group, whereas all the patients in the conventional-laser group completed the entire PRP treatment in two or three sessions. Persistence and/or recurrence of neovascularization, complications encountered, total number of laser spots, and mean power used were compared. Patients treated with the PASCAL received significantly higher number of laser spots than those treated with conventional laser (2885 vs. 1642, p < 0.001). The PASCAL and conventional-laser systems required an average power of 650 mW and 330 mW, respectively (p < 0.001). Patients treated with the PASCAL showed similar rates of treatment failure within 12 months of follow-up compared with patients treated with conventional laser (14% vs. 11%, p > 0.05). In the PASCAL group, vitreous hemorrhage, neovascular glaucoma, retinal hemorrhage, and choroidal detachment were reported in two, two, one, and two patients, respectively, whereas only one each vitreous hemorrhage and neovascular glaucoma were encountered in the conventional-laser group. Our study reports that single-session PRP with the PASCAL has similar efficacy compared with conventional laser, and has a favorable side-effect profile. PMID- 26853169 TI - Off-treatment efficacy of 3-year nucleos(t)ide analogues in chronic hepatitis B patients. AB - Lamivudine, telbivudine, and entecavir are the first-line drugs covered by the Taiwan National Health Insurance as 3-year treatments for patients with chronic hepatitis B virus (HBV), but the optimal treatment duration of each remains unclear. We aimed to detect HBV treatment-cessation durability, and compare the predictors in patients with and without clinical relapse. In this retrospective cohort study, 210 patients with chronic HBV who tested hepatitis B e-antigen positive or hepatitis B e-antigen negative were treated for 3 years with a nucleos(t)ide analogue. Of these, 102 patients continued therapy after 3 years, while 88 patients stopped treatment and were followed for 1 year due to financial difficulties. Efficacy was assessed in terms of alanine aminotransferase (ALT) level normalization, HBV DNA clearance, virus breakthrough, clinical relapse, and liver decompensation. The durability predictors were evaluated by host factors, HBV DNA, and drug differences. Eighty patients (14 on lamivudine, 19 on telbivudine, and 47 on entecavir) were recruited. There was no difference in clinical-relapse rate among lamivudine, telbivudine, and entecavir (35.7% vs. 36.8% vs. 31.9%, respectively; p = 0.916), and liver decompensated hepatitis was absent. In baseline clinical characteristics, there were no differences between the clinical-relapse and nonrelapse groups in age, sex, cirrhosis, prior treatment, HBV DNA, pretreatment ALT, or hepatitis B e-antigen (HBeAg). The mean 3(rd) year serum ALT level differed significantly between clinical-relapse and nonrelapse patients (37.5 U/L vs. 27.7 U/L, respectively; p = 0.044). The 3-year nucleos(t)ide analogue off-treatment in patients with chronic HBV delivered according to the Taiwan National Health Insurance guidelines had an overall 33.8% 1-year clinical-relapse rate without any decompensated hepatitis flare-ups. PMID- 26853170 TI - Robotic partial nephrectomy for clinical stage T1 tumors: Experience in 42 cases. AB - The aim of this study was to evaluate outcomes of robotic partial nephrectomy (RAPN) procedures. At two centers, 42 patients underwent RAPN. Radius, Exo/Endophytic, Nearness, Anterior/Posterior, Location (R.E.N.A.L.) nephrometry and PADUA scores of patients were calculated by computed tomography (CT) or magnetic resonance imaging (MRI). Intra- and perioperative (0-30 days) complications were evaluated using modified Clavien classification. A four-arm da Vinci-S robotic surgical system was used and outcomes were evaluated retrospectively. Mean age of the patients was 52.3 +/- 6.5 years. Mean tumor size was 3.1 +/- 1.0 (1.4-6.6) cm. R.E.N.A.L. nephrometry and PADUA scores were 6.0 +/ 1.5 and 7.5 +/- 0.9, respectively. Mean surgical time was 127.7 +/- 18.7 minutes and estimated blood loss was 100 +/- 18.1 cc. Mean warm ischemia time was 16.0 +/ 8.9 (0-30) minutes. Intraoperative complications did not develop in any patient. Median hospital stay was 3.0 (2-6) days. Except for 17 patients, hilar clamping was performed in 25 patients. Histopathology results included 34 renal cell carcinoma (22 clear cell, 7 chromophobe cell, 4 papillary cell, and 1 clear papillary cell). Oncocytoma (n = 4), adenoma (n = 1), fibroadipose tissue (n = 1), papillary epithelial hyperplasia (n = 1), and chronic pyelonephritis (n = 1) were present. Surgical margins were negative in all patients. During a median follow-up period of 15.5 +/- 10.9 (3-46) months, neither local recurrence nor distant metastasis was detected. In conclusion, RAPN is a safe, minimally invasive surgical approach, with excellent surgical and oncological outcomes in T1 kidney tumors. Zero ischemia off-clamp RAPN is also safe in selected masses with the advantage of avoiding complete renal ischemia. PMID- 26853172 TI - Clinical, diagnostic and therapeutic management of patients with breast tuberculosis: Analysis of 46 Cases. AB - Breast tuberculosis is a rare form of extrapulmonary tubercular infection. Our aim is to highlight the nonspecific clinical presentations, diagnostic difficulties and therapeutic approaches of mammarian tuberculosis. Forty-six patients diagnosed with breast tuberculosis between 2005 and 2015 were reviewed retrospectively. Clinical features, all diagnostic methods, and the outcomes of treatment were analysed. All cases were female with a mean age of 36.4 years. Breast mass and pain were the most common complaints. While 34.8% of the cases had a physical examination with suspicions for malignancy, 43.5% of the patients had Breast Imaging Reporting and Data System (BI-RADS) 4 or 5 lesions suggested malignancy radiologically. Definitive diagnosis was based on histopathologic examination through core needle biopsy (n = 29), excisional biopsy (n = 12), and open biopsy (n = 5) taken from the abscess wall during drainage. Standard antiTB therapy for 6 months was given to all cases. Thirty-three patients recovered with standard 6-month therapy while extended treatment for 9-12 months was needed in 13 (28.2%) cases. Surgery was carried out in 17 cases. Two patients developed recurrence. Breast tuberculosis can be easily confused with breast cancer, suppurative abscess, and other causes of granulomatous mastitis, both clinically and radiologically. A multidisciplinary approach is required to prevent diagnostic delays and unnecessary surgical interventions. Although antiTB therapy is the mainstay treatment of breast TB, surgery is usually indicated in patients refractory to medical treatment. PMID- 26853173 TI - Desflurane reinforces the efficacy of propofol target-controlled infusion in patients undergoing laparoscopic cholecystectomy. AB - Whether low-concentration desflurane reinforces propofol-based intravenous anesthesia on maintenance of anesthesia for patients undergoing laparoscopic cholecystectomy is to be determined. The aim of this study was to investigate whether propofol-based anesthesia adding low-concentration desflurane is feasible for laparoscopic cholecystectomy. Fifty-two patients undergoing laparoscopic cholecystectomy were enrolled in the prospective, randomized, clinical trial. Induction of anesthesia was achieved in all patients with fentanyl 2 MUg/kg, lidocaine 1 mg/kg, propofol 2 mg/kg, and rocuronium 0.8 mg/kg to facilitate tracheal intubation and to initiate propofol target-controlled infusion (TCI) to effect site concentration (Ce: 4 MUg/mL with infusion rate 400 mL/h). The patients were then allocated into either propofol TCI based (group P) or propofol TCI adding low-concentration desflurane (group PD) for maintenance of anesthesia. The peri-anesthesia hemodynamic responses to stimuli were measured. The perioperative psychomotor test included p-deletion test, minus calculation, orientation, and alert/sedation scales. Group PD showed stable hemodynamic responses at CO2 inflation, initial 15 minutes of operation, and recovery from general anesthesia as compared with group P. There is no significant difference between the groups in operation time and anesthesia time, perioperative psychomotor functional tests, postoperative vomiting, and pain score. Based on our findings, the anesthetic technique combination propofol and desflurane for the maintenance of general anesthesia for laparoscopic cholecystectomy provided more stable hemodynamic responses than propofol alone. The combined regimen is recommended for patients undergoing laparoscopic cholecystectomy. PMID- 26853174 TI - Effects of dorzolamide/timolol fixed combination on retrobulbar hemodynamics in pseudoexfoliative glaucoma. AB - In our study we aimed to evaluate the short-term effects of dorzolamide/timolol on ocular perfusion pressure and retrobulbar blood flow in patients with pseudoexfoliative glaucoma (PXG). This prospective observational cross-sectional study enrolled 22 eyes of 22 newly-diagnosed patients with PXG in a single center. All of the patients received a fixed combination of dorzolamide/timolol. Besides routine ophthalmologic examination, the retrobulbar hemodynamic parameters in the ophthalmic artery, central retinal artery, and short posterior ciliary arteries were measured in all participants at baseline and the 3(rd) month using color Doppler imaging. The mean intraocular pressure (IOP) was 22.3 +/- 2.1 mmHg at baseline and reduced to 17.4 +/- 2.3 mmHg at the 3(rd) month (p < 0.05). None of the retrobulbar parameters, except peak systolic velocity and resistive index in temporal short posterior ciliary arteries, changed significantly on therapy with dorzolamide/timolol fixed combination when the results were analyzed at Month 3. The drug significantly decreased the peak systolic velocity (p = 0.044) and reduced the resistive index in 0.04 units, 95% confidence interval 0.03-0.05, (p < 0.001) in the temporal short posterior ciliary arteries. This study reports that the retrobulbar hemodynamics might be affected less than expected by dorzolamide/timolol fixed combination in patients with PXG although the reduction of IOP was statistically significant. PMID- 26853176 TI - A lesion mimicking malignancy in the cesarean scar: Decidualize endometriosis. PMID- 26853175 TI - Relationship of cumulative dust exposure dose and cumulative abnormal rate of pulmonary function in coal mixture workers. AB - To investigate the dose-response relationship between cumulative dust exposure (CDE) and cumulative abnormal rate of pulmonary function in coal mixture workers. Three hundred and twenty eight coal mixture workers (exposed group) and 169 nondust-exposed workers (control group) were recruited. Basic information data were collected and pulmonary function tests were performed. Pulmonary function was compared between the two groups after comparing smoking behaviors. Pulmonary function indices [forced vital capacity in 1 second after full inspiration (FVC)%, forced expiratory volume (FEV)1%, and FEV1/FVC%] were compared among groups stratified by service length (exposure duration). The relationship between CDE dose and cumulative abnormal rate of pulmonary function in coal mixture workers was analyzed. Abnormal rate of pulmonary function in the exposed group (35.1%) was significantly higher than the control group (10.1%; p < 0.001); FVC%, FEV1%, and FEV1/FVC% in the exposed group decreased significantly compared with the control group (all p < 0.05). Differences in FVC%, FEV1%, and FEV1/FVC% among coal mixture workers stratified by exposure duration in the exposed group were statistically significant (all p < 0.05). The discernible increase in the cumulative abnormal rate was observed, from >= 1000 mg/m(3).years group to >= 1700 mg/m(3).years group. Correlation analysis revealed a positive correlation between the CDE dose and the cumulative abnormal rate of pulmonary function. Higher abnormal pulmonary function rate was found among coal mixture workers, characterized by decreased pulmonary function indices. Our results suggested a positive relationship between CDE dose and cumulative abnormal pulmonary function rate, and a rapid increase in cumulative abnormal rate within a certain range of CDE dose. A lower limit value of 1000 mg/m(3).years has reference significance. PMID- 26853177 TI - Cerebellar cognitive affective syndrome: Attention deficit-hyperactivity disorder episode of adolescent with cerebellar atrophy in a psychiatric ward. PMID- 26853178 TI - Factors associated with biopsy site identification, postponement of surgery, and patient confidence in a dermatologic surgery practice. AB - BACKGROUND: Biopsy site identification is critical to avoid wrong-site surgery and may impact patient-centered outcomes. OBJECTIVE: We sought to evaluate risk factors for biopsy site misidentification, postponement of surgery, and patient confidence in surgical site selection and to assess the near-miss rate for wrong site surgeries. METHODS: This was a prospective observational cohort study. RESULTS: Near-miss wrong-site surgeries were detected and averted in 1.3% (3 of 239) of patients with biopsy site photographs. Risk factors for biopsy site misidentification by patients were 6 weeks or longer between biopsy and surgery (odds ratio [OR] 2.19, 95% confidence interval [CI] 1.12-4.27; P = .028) and patient inability to see biopsy site (OR 3.95, 95% CI 1.50-10.37; P = .002). Risk factors for physician misidentification were 6 or more weeks between biopsy and surgery (OR 3.68, 95% CI 1.40-9.66; P = .007) and biopsy specimens from multiple sites (OR 4.39, 95% CI 1.67-11.54; P = .003). Postponement of surgery was associated with absence of a biopsy site photograph (OR 12.5, 95% CI 2.79-62.21; P < .001). Patient confidence in surgical site identification was associated with the presence of a biopsy site photograph (OR 5.48, 95% CI 1.96-15.30; P = .001). LIMITATIONS: This was a single-site observational study. CONCLUSION: Biopsy site photography is associated with reduced rates of postponed surgeries and improved rates of patient confidence in surgical site selection. Risk factors for biopsy site misidentification should be considered before definitive treatment. PMID- 26853179 TI - Keratoacanthoma (KA): An update and review. AB - Keratoacanthoma (KA) is a common but underreported tumor of the skin. Two striking features of KA are its clinical behavior with spontaneous regression after rapid growth and its nosological position on the border between benignity and malignancy. We review current knowledge on the clinical, histopathological, and dermoscopic features of KA to ensure a proper diagnosis and describe its variants, including different types of multiple KAs. We highlight current concepts of KA ethiopathogenesis with special emphasis on the genetic background of multiple familial KA, the role of Wnt signaling pathway, and induction of KA by BRAF inhibitors and procedures of esthetic dermatology. Finally, treatment strategies are presented with surgical excision as a first option, followed by other modalities, including intralesional chemotherapy, topical and systemic agents, lasers, cryotherapy, and photodynamic therapy. PMID- 26853181 TI - Atomic MoS2 monolayers synthesized from a metal-organic complex by chemical vapor deposition. AB - The controllable synthesis of MoS2 monolayers is the key challenge for their practical applications. Here we report the chemical vapor deposition (CVD) growth of single layered MoS2 by utilizing a bifunctional precursor. This precursor is a metal-organic complex which supplies both Mo sources and organic seeding promoters for the efficient CVD growth of MoS2 monolayers. The successful growth of high quality MoS2 flakes indicates that the rational design of bifunctional precursors will open up a new way for the controllable CVD growth of two dimensional (2D) transition metal dichalcogenides (TMDCs). PMID- 26853182 TI - Association of physical activity with risk of metabolic syndrome: findings from a cross-sectional study conducted in rural area, Nantong, China. AB - The prevalence of metabolic syndrome increases rapidly worldwide, and its association with physical activity (PA) varies with race and lifestyles. Little is known about the association in rural China. The Nantong Metabolic Syndrome Study recruited 13,505 female and 6997 male participants in 2007 and 2008. Socio demographic characteristics, and physiological and behavioural data were collected. Logistic regression model was applied to estimate associations of metabolic syndrome and its components with different PAs. The overall metabolic syndrome prevalence was 21.6% in current study. Increasing total PA or moderate to-vigorous-intensity occupational PA was associated with decreasing 5%-60% risk of having metabolic syndrome and abnormal metabolic syndrome components in both genders. An association between leisure-time PA and blood pressure was found in men, but no associations between leisure-time PA and metabolic syndrome components were found in women. Commuting PA, such as walking and taking bus, by bicycle and walking only, was associated with decrease of 20%-45% risk of several abnormal metabolic syndrome components in women. This study provides information for future investigation into the nature of these associations so that recommendations can be developed to reduce the prevalence of metabolic syndrome and its components among rural population in China. PMID- 26853183 TI - Some adverse effects of soil amendment with organic Materials-The case of soils polluted by copper industry phytostabilized with red fescue. AB - The study was aimed to examine the effects of soil amendment with organic waste materials on the growth of red fescue and the uptake of Cu and Zn by this grass, in view of its potential usage for phytostabilization of Cu-polluted soils. Five soils, containing 301-5180 mg/kg Cu, were collected from the surroundings of copper smelter Legnica, and amended with lignite (LG) and limed sewage sludge (SS). Plant growth and the concentrations of Cu and Zn in the shoots and roots of grass were measured in a pot experiment and related to the results of Pytotoxkit and Microtox(r) tests performed on soil solution. The effects of soil amendment with LG and SS differed greatly, and depended on soil properties. In some cases, the application of alkaline SS resulted in dramatic increase of Cu phytotoxicity and its enhanced uptake by plants, while application of LG to slightly acidic soil caused increased accumulation of Zn in plants, particularly in their roots. The study confirmed good suitability of red fescue for phytostabilization of Cu contaminated soils except for those extremely polluted. Organic amendments to be used for metal immobilization should be thoroughly examined prior to application. PMID- 26853180 TI - Comparative effectiveness of biologic agents for the treatment of psoriasis in a real-world setting: Results from a large, prospective, observational study (Psoriasis Longitudinal Assessment and Registry [PSOLAR]). AB - BACKGROUND: Comparing effectiveness of biologics in real-world settings will help inform treatment decisions. OBJECTIVES: We sought to compare therapeutic responses among patients initiating infliximab, adalimumab, or etanercept versus ustekinumab during the Psoriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: Proportions of patients achieving a Physician Global Assessment score of clear (0)/minimal (1) and mean decrease in percentage of body surface area with psoriasis were evaluated at 6 and 12 months. Adjusted logistic regression (Physician Global Assessment score 0/1) and analysis of covariance (percentage of body surface area with psoriasis) were performed to determine treatment factors associated with effectiveness. RESULTS: Of 2541 new users on registry, 2076 had efficacy data: ustekinumab (n = 1041), infliximab (n = 116), adalimumab (n = 662), and etanercept (n = 257). Patients receiving tumor necrosis factor-alpha( alpha) inhibitors were significantly less likely to achieve Physician Global Assessment score 0/1 versus ustekinumab (infliximab [odds ratio {OR} 0.396, P < .0001], adalimumab [OR 0.686, P = .0012], etanercept [OR 0.554, P = .0003] at 6 months and infliximab [OR 0.449, P = .0040] at 12 months). Mean decrease in percentage of body surface area with psoriasis was significantly greater for ustekinumab versus adalimumab (point estimate 1.833, P = .0020) and etanercept (point estimate 3.419, P < .0001) at 6 months and versus infliximab (point estimate 3.945, P = .0005) and etanercept (point estimate 2.778, P = .0007) at 12 months. LIMITATIONS: Treatment selection bias and limited data for doing adjustments are limitations. CONCLUSIONS: In PSOLAR, effectiveness of ustekinumab was significantly better versus all 3 tumor necrosis factor-alpha inhibitors studied for the majority of comparisons at 6 and 12 months. PMID- 26853184 TI - Family needs at a post-acute rehabilitation setting and suggestions for supports. AB - OBJECTIVE: To explore the perceived needs, obstacles to services, psychological distress and social problem-solving abilities of family members of persons with ABI at a post-acute community-based brain injury rehabilitation facility and offer suggestions for methods of assessment and providing support. PARTICIPANTS: Twenty-nine family members who did not provide daily care, but were involved in the care process. DESIGN: Participants completed self-report questionnaires including the FNQ:R, SOS, DASS-21, WHO-QOL BREF and SPSI:R-S. RESULTS: Participants reported informational and professional needs as most met and involvement in care, instrumental support and emotional support as most unmet. Most were satisfied with the amount of professional help and services and had confidence in the quality of care. Nearly half of the family members felt there were few ABI-related resources in the community and one third were unaware of good ABI treatment resources in their community. Psychosocial functioning was generally average. CONCLUSION: Family members who do not provide daily care are still impacted by the neurobehavioural changes that progress throughout the long term, post-acute community phase. This study offers suggestions regarding an effective methodology for assessing family needs and recommends accessible and practical supports. PMID- 26853185 TI - Molecular structure and vibrations of NTCDA monolayers on Ag(111) from density functional theory and infrared absorption spectroscopy. AB - The structure and vibrational properties of the metal-organic interface of 1,4,5,8-naphthalene-tetracarboxylic dianhydride (NTCDA) on Ag(111) were analysed using Fourier-transform infrared absorption spectroscopy in conjunction with density functional theory calculations including dispersion forces (PBE-D3). Mode assignments and polarizations as well as molecular distortions were determined for four adsorption geometries of NTCDA on top and bridge sites aligned either parallel or perpendicular to the Ag rows and compared to accurate calculations of the free molecule. This enables an in-depth understanding of surface effects on the computed and experimental vibrational spectra of the adsorbed NTCDA molecule. The molecule-substrate interaction comprises two major and equally important contributions: non-directional van der Waals forces between molecule and surface, and covalent bonding of the acyl oxygen atoms with underlying Ag atoms, which is quantified by charge-transfer analysis. Furthermore, adsorption energy calculations showed that the molecular axis of flat-lying NTCDA is oriented preferably in parallel to the Ag rows. The molecule is subject to particular distortions from the planar gas phase structure with covalent bonding leading to downward bending of the acyl oxygen atoms and Pauli repulsion to upward bending of the carbon core. In parallel, strong buckling of the silver surface was identified. As found in previous studies, the lowest unoccupied molecular orbital (LUMO) of the molecule slips below the Fermi level and becomes partially populated upon adsorption. Excitation of totally symmetric vibrational modes then leads to substantial interfacial dynamical charge transfer, which is convincingly reproduced in the calculated IR spectra. PMID- 26853186 TI - Observation of alpha-Helical Hydrogen-Bond Cooperativity in an Intact Protein. AB - The presence and extent of hydrogen-bonding (H-bonding) cooperativity in proteins remains a fundamental question, which in the past has been studied extensively, mostly by infrared and fluorescence measurements on model peptides. We demonstrate that such cooperativity can be studied in an intact protein by hydrogen/deuterium exchange NMR spectroscopy. The method is based on the fact that substitution of NH by ND in a backbone amide group slightly weakens the N H...O?C hydrogen bond. Our results show that such substitution at position i in an alpha-helix impacts the (1)H and (15)N chemical shifts of the amide sites of residues i - 3 to i + 3. Quantum mechanical calculations indicate that the upfield shifts of (1)H and (15)N resonances at site i, observed upon H/D exchanges at sites i - 3, i + 1, i + 2, and i + 3, correspond to a decrease of the ith backbone amide electric dipole moment, which weakens its H-bonding and long-range electrostatic interactions with other backbone amides in the alpha helix. These results provide new quantitative insights into the cooperativity of H-bonding in protein alpha-helices. PMID- 26853187 TI - A novel photoacoustic nanoprobe of ICG@PEG-Ag2S for atherosclerosis targeting and imaging in vivo. AB - Atherosclerosis is a major cause of cardiovascular and cerebrovascular diseases that have high mortality and disability rates. Because of its unclear pathogenic mechanism and heterogeneous distribution feature, it is still a big challenge to achieve precise diagnosis and therapy of atherosclerosis at its early stage in vivo. Herein, we fabricated a new ICG@PEG-Ag2S nanoprobe by a simple self assembly of DT-Ag2S QDs, amphipathic C18/PEG polymer molecules and ICG. The ICG@PEG-Ag2S nanoprobe showed relatively long blood retention and was selectively accumulated in the region of atherosclerotic plaque due to the lipophilicity of the C18 chain to the atherosclerosis microenvironment, and thus the atherosclerosis was real-time monitored by high contrast-enhanced photoacoustic (PA) imaging of ICG. Combining the high signal-to-noise ratio (SNR) and high spatial resolution fluorescence imaging of Ag2S QDs in the second near-infrared window (NIR-II) and related histological assessment in vitro, the feasibility of this new nanoprobe for atherosclerosis targeting in an Apoe(-/-) mouse model was verified. Additionally, hemolysis and coagulation assays of the ICG@PEG-Ag2S revealed its decent hemocompatibility and no histological changes were observed in the main organs of the mouse. Such a simple, multifunctional nanoprobe for targeting and PA imaging of atherosclerosis will have a great potential for future clinical applications. PMID- 26853189 TI - Hierarchical mesoporous NiCo2O4 hollow nanocubes for supercapacitors. AB - In the present work, mesoporous NiCo2O4 hollow nanocubes are synthesized using a "coordinating etching & precipitating" (CEP) route. The hollow nanocubes are characterized using SEM, TEM, XRD, XPS and BET methods. The hollow nanocubes have a uniform morphology of 300-500 nm, a high surface area of 134.52 m(2) g(-1) and a mesoporous structure of 2.4-6 nm. These mesoporous NiCo2O4 hollow nanocubes exhibit the specific capacitance of 795.6 F g(-1) at a constant discharge current density of 1 A g(-1). The high specific capacitance and the stability of the NiCo2O4 hollow nanocube electrode are attributed to its large specific surface area and mesoporous structure. The specific capacity retention is 97.5% at a current density of 1 A g(-1) and 96.1% at a current density of 2 A g(-1) over 2000 charge-discharge cycles. The high specific capacitance and excellent cyclic stability indicate that NiCo2O4 hollow nanocubes are excellent supercapacitor electrode materials. PMID- 26853188 TI - Expression, purification, and characterization of recombinant human H-chain ferritin. AB - Based on their nanocage architectures, ferritins show their potential applications in medical imaging and therapeutic delivery systems. However, the recombinant human H-chain ferritin (rHF) is prone to form inclusion bodies in Escherichia coli. In our study, the cDNA of rHF was cloned into plasmid pET28a under the control of a T7 promoter. Molecular chaperones, including GroES, GroEL, and trigger factor, were coexpressed with rHF to facilitate its correct folding. The results showed that the solubility of rHF was increased more than threefold with the help of molecular chaperones. Taking advantages of its N-terminal His tag, rHF was then purified with Ni-affinity chromatography. With a yield of 15 mg/L from bacterial culture, the purified rHF was analyzed by circular dichroism spectrometry for its secondary structure. Moreover, the rHF nanocages were characterized by transmission electron microscopy and dynamic light scattering. Our results indicate that rHF is able to self-assemble into nanocages with a narrow size distribution. PMID- 26853190 TI - A voltage-controlled silver nanograting device for dynamic modulation of transmitted light based on the surface plasmon polariton effect. AB - An active-controlled plasmonic device is designed and fabricated based on the index-sensitive properties of surface plasmon polaritons (SPPs). We utilize a one dimensional silver nanograting with a period of 320 nm overlayered with a liquid crystal (LC) layer (50 MUm in thickness), to transmit selectively the surface plasmon resonance (SPR) wavelength. This device realizes the active, reversible and continuous control of the transmitted light wavelength by modulating the external voltage signal applied to the LC layer. This voltage-controlled plasmonic filter has a dynamic wavelength modulation range of 17 nm, a fast respond speed of 4.24 ms and a low driving voltage of 1.06 V MUm(-1). This study opens up a unique way for the design of tunable nanophotonic devices, such as a micro light sources and switches. PMID- 26853191 TI - Randomized controlled trial of mindfulness-based stress reduction (MBSR) on posttraumatic growth of Chinese breast cancer survivors. AB - Breast cancer (BC) patients in China suffered from a variety of psychology stress such as perceived stress and anxiety, posttraumatic growth (PTG) as a positive factor could promote their psychology health and quality of life. This study aimed to investigate the efficacy of mindfulness-based stress reduction (MBSR) on promoting PTG, decreasing perceived stress and anxiety of Chinese BC patients. A randomized controlled trial of 60 BC patients (Stages I-III) was conducted. They were randomly divided to the 8-week MBSR group or usual care (UC) group. PTG inventory, Perceived Stress Scale of Chinese version (CPSS) and State Trait Anxiety Inventory (STAI) evaluated the PTG level, perceived stress and anxiety at three times(before intervention-T1, after intervention-T2 and follow up at 3 months-T3). A repeated-measures analysis of variance model was used to compare each outcome measure of two groups at the three times. There was one patient discontinued the intervention and one lose to follow up in MBSR group, finally 58 BC patients completed the research. There was no difference between two groups before the intervention. The results showed significant improvements in MBSR group comparing with the UC group that PTG level was much higher after the 8-week intervention and the follow up (F = 34.73, p < .00). At the same time, CPSS (F = 14.41, p < .00) and STAI (F = 15.24, p < .00) scores were significant decreased at T2 and T3. The results showed that MBSR promoted the level of PTG and decreased perceived stress and anxiety state of Chinese BC patients, and the results persisted at three months after intervention. The research preliminary proved that MBSR was suitable to Chinese BC patients. MBSR should be recommending to BC survivors in China. PMID- 26853192 TI - Prevalence of comorbidity in primary care patients with type 2 diabetes and its association with elevated HbA1c: A cross-sectional study in Croatia. AB - OBJECTIVE: To the authors' knowledge, there are few valid data that describe the prevalence of comorbidity in type 2 diabetes mellitus (T2DM) patients seen in family practice. This study aimed to investigate the prevalence of comorbidities and their association with elevated (>= 7.0%) haemoglobin A1c (HbA1c) using a large sample of T2DM patients from primary care practices. DESIGN: A cross sectional study in which multivariate logistic regression was applied to explore the association of comorbidities with elevated HbA1c. SETTING: Primary care practices in Croatia. SUBJECTS: Altogether, 10 264 patients with diabetes in 449 practices. MAIN OUTCOME MEASURES: Comorbidities and elevated HbA1c. RESULTS: In total 7979 (77.7%) participants had comorbidity. The mean number of comorbidities was 1.6 (SD 1.28). Diseases of the circulatory system were the most common (7157, 69.7%), followed by endocrine and metabolic diseases (3093, 30.1%), and diseases of the musculoskeletal system and connective tissue (1437, 14.0%). After adjustment for age and sex, the number of comorbidities was significantly associated with HbA1c. The higher the number of comorbidities, the lower the HbA1c. The prevalence of physicians' inertia was statistically significantly and negatively associated with the number of comorbidities (Mann-Whitney U test, Z = 12.34; p < 0.001; r = -0.12). CONCLUSION: There is a high prevalence of comorbidity among T2DM patients in primary care. A negative association of number of comorbidities and HbA1c is probably moderated by physicians' inertia in treatment of T2DM strictly according to guidelines. KEY POINTS: There is a high prevalence of comorbidity among T2DM patients in primary care. Patients with breast cancer, obese patients, and those with dyslipidaemia and ischaemic heart disease were more likely to have increased HbA1c. The higher the number of comorbidities, the lower the HbA1c. PMID- 26853193 TI - Demonstration of a modelling-based multi-criteria decision analysis procedure for prioritisation of occupational risks from manufactured nanomaterials. AB - Several tools to facilitate the risk assessment and management of manufactured nanomaterials (MN) have been developed. Most of them require input data on physicochemical properties, toxicity and scenario-specific exposure information. However, such data are yet not readily available, and tools that can handle data gaps in a structured way to ensure transparent risk analysis for industrial and regulatory decision making are needed. This paper proposes such a quantitative risk prioritisation tool, based on a multi-criteria decision analysis algorithm, which combines advanced exposure and dose-response modelling to calculate margins of exposure (MoE) for a number of MN in order to rank their occupational risks. We demonstrated the tool in a number of workplace exposure scenarios (ES) involving the production and handling of nanoscale titanium dioxide, zinc oxide (ZnO), silver and multi-walled carbon nanotubes. The results of this application demonstrated that bag/bin filling, manual un/loading and dumping of large amounts of dry powders led to high emissions, which resulted in high risk associated with these ES. The ZnO MN revealed considerable hazard potential in vivo, which significantly influenced the risk prioritisation results. In order to study how variations in the input data affect our results, we performed probabilistic Monte Carlo sensitivity/uncertainty analysis, which demonstrated that the performance of the proposed model is stable against changes in the exposure and hazard input variables. PMID- 26853194 TI - Emerging pests and diseases of South-east Asian cassava: a comprehensive evaluation of geographic priorities, management options and research needs. AB - Cassava is a major staple, bio-energy and industrial crop in many parts of the developing world. In Southeast Asia, cassava is grown on >4 million ha by nearly 8 million (small-scale) farming households, under (climatic, biophysical) conditions that often prove unsuitable for many other crops. While SE Asian cassava has been virtually free of phytosanitary constraints for most of its history, a complex of invasive arthropod pests and plant diseases has recently come to affect local crops. We describe results from a region-wide monitoring effort in the 2014 dry season, covering 429 fields across five countries. We present geographic distribution and field-level incidence of the most prominent pest and disease invaders, introduce readily-available management options and research needs. Monitoring work reveals that several exotic mealybug and (red) mite species have effectively colonised SE Asia's main cassava-growing areas, occurring in respectively 70% and 54% of fields, at average field-level incidence of 27 +/- 2% and 16 +/- 2%. Cassava witches broom (CWB), a systemic phytoplasma disease, was reported from 64% of plots, at incidence levels of 32 +/- 2%. Although all main pests and diseases are non-natives, we hypothesise that accelerating intensification of cropping systems, increased climate change and variability, and deficient crop husbandry are aggravating both organism activity and crop susceptibility. Future efforts need to consolidate local capacity to tackle current (and future) pest invaders, boost detection capacity, devise locally-appropriate integrated pest management (IPM) tactics, and transfer key concepts and technologies to SE Asia's cassava growers. Urgent action is needed to mobilise regional as well as international scientific support, to effectively tackle this phytosanitary emergency and thus safeguard the sustainability and profitability of one of Asia's key agricultural commodities. (c) 2016 Society of Chemical Industry. PMID- 26853195 TI - American Indian and Alaska Native Access to Oral Health Care: A Potential Solution. AB - American Indians and Alaska Natives (AI/AN) experience significant health disparities relative to the general U.S. POPULATION: In particular, oral diseases affect the majority of the AI/AN population and their prevalence is significantly greater than observed in other demographic sectors of the U.S. POPULATION: The reasons for these disparities are multiple but lack of access to dental care is clearly a contributing factor. The dentist-to-population ratio in many AI/AN communities is less than half the U.S. average. A solution has been developed in Alaska by AI/AN leaders: dental therapists, i.e., local people trained for two years to provide basic dental services. This solution is being fought by organized dentistry that sees the approach as an economic threat, but AI/AN organizations are committed to implementing this Native solution to their access problem. The Alaska experience indicates that access to oral health services can be improved through the addition of dental therapists to the dental team. PMID- 26853196 TI - Historical Consequences of Colonialism, Disempowerment, and Reactionary Government Decisions in Relation to Imprisonment Rates in Australia's Northern Territory: A Potential Solution. AB - The Northern Territory (N.T.) of Australia has the highest imprisonment rate per capita in the country. The vast majority of prisoners (86%) are Indigenous Australian despite only 30% of the N.T. population identifying as Indigenous. This paper investigates factors influencing this over-representation. The most common reason for imprisonment concerns violence. Alcohol is consumed in high quantities, particularly in Central Australia and is thought to affect incarceration rates. Recent strategies to control alcohol abuse in the N.T. have been ineffective in comparison with other states of Australia. Notwithstanding that crimes committed are serious enough to warrant arrest, the cumulative effects of past and recent history have resulted in poor educational outcomes for Indigenous Australian children which influence employment opportunities. Solutions to reduce imprisonment must address the nexus between education, meaningful employment and community-led alcohol management strategies. Failure to adopt this approach may perpetuate ever-increasing imprisonment of Indigenous Australians. PMID- 26853197 TI - Historical Factors, Discrimination and Oral Health among Aboriginal Australians. AB - Discrimination is a very real facet of Australian Aboriginal and Torres Strait Islander (ATSI) life. Paradies has detailed the strong links between racism and chronic stress and the influence this may have on general health, confounding the pre-supposed notion that ATSI populations are more genetically predisposed to chronic diseases. For example a genetic predisposition promoting central adipose storage in populations with recent (in evolutionary terms) changes to hunter gatherer dietary patterns is thought to contribute to the higher rates of diabetes seen in ATSI and other Native populations. This relationship, however, is far from causal in any straight-forward way. In support of the work by Paradies, research from the U.S. also shows that racism, both explicit and subtle, contributes to chronic disease and suffering among ethnic minorities. While the exploration of the perceived or self-reported racial discrimination is recent, this concept has increasing evidence to support its relationship to poor health outcomes. PMID- 26853198 TI - Developing a Sustainable Model of Oral Health Care for Disadvantaged Aboriginal People Living in Rural and Remote Communities in NSW, Using Collective Impact Methodology. AB - A sustainable model of oral health care for disadvantaged Aboriginal people living in rural and remote communities in New South Wales was developed using collective impact methodology. Collective impact is a structured process which draws together organizations to develop a shared agenda and design solutions which are jointly resourced, measured and reported upon. PMID- 26853199 TI - Quality Improvement: Indigenous Influence in Oral Health Policy, Process, and Practice. AB - A Quality Improvement Group for Maori oral health providers [Indigenous New Zealand oral health services] has been an effective and necessary mechanism for engaging Indigenous oral health expertise in decision-making for Indigenous oral health policy and sector developments to reduce oral health inequalities and improve Indigenous oral health outcomes. PMID- 26853200 TI - Nganampa Health Council Dental Program: Remote Dentistry in the Australian Desert -Partnership or Perish. AB - The Nganampa Health Council (literally "Our Health Council") is an Aboriginal community-controlled Primary Health Care service established in 1983. It was born out of the political struggle for Aboriginal Land Rights in South Australia which culminated in The Anangu Pitjantjatjara Yankunytjatjara (APY) Land Rights Act, 1981, a milestone in Indigenous Land Rights both in Australia and internationally. PMID- 26853201 TI - Factors Associated with Routine Dental Attendance among Aboriginal Australians. AB - OBJECTIVES: To determine factors associated with routine dental attendance in Aboriginal Australians. METHODS: Data of 271 Aboriginal adults residing in Australia's Northern Territory were used. Routine dental attendance was defined as last visiting a dentist less than one year ago or visiting a dentist for a check-up. Both bivariate and multivariable analytical techniques were used. RESULTS: While 27% visited a dentist in the past year, 29% of these visited for a check-up. In bivariate analysis, being female, low psychological distress, and low clinical attachment loss (CAL) were associated with visiting a dentist within last year. Being aged younger than 39 years, male, no oral health impairment, being caries-free, low CAL, and low apolipoprotein B were associated with visiting for a check-up. Clinical attachment loss remained associated with visiting a dentist less than one year ago while being younger than 39 years and having no oral health impairment remained associated with usually visiting for a check-up in multivariable analysis. CONCLUSIONS: Younger age, no oral health impairment, and low CAL were associated with routine dental attendance among Indigenous Australians. PMID- 26853202 TI - Income as a Protective Factor for Dental Caries among Indigenous People from Central Brazil. AB - The objective of this paper was to evaluate the association between eligibility for a conditional cash transfer program, based on household income, and dental caries in 12-year-old children from three Indigenous ethnic groups living in Mato Grosso do Sul state, Central Brazil. A population-based cross-sectional study was performed in three ethnic groups: Kaiwoa, Guarani, and Terena. The study population was drawn by stratified sampling according to each ethnic group with a probability proportional to the village size. The number of untreated decayed permanent teeth as a count variable was the outcome measure. Ethnic group and eligibility for the conditional cash transfer program showed significant association with untreated caries. Children from Guarani and Terena presented respectively two-fold and 2.8-fold higher caries rate (p<.001) compared with Kaiwoa in the adjusted model, while children from no eligible cash transfer program households had a 40% lower caries rate (p=.034). PMID- 26853203 TI - Service Use and Perceived Need among an Aboriginal Population in Western Australia. AB - Limited information is available about dental service use, perceived need and perceived oral health status among Aboriginal populations in Western Australia. This study collected information from a convenience sample of people attending the opening ceremony of the 2014 National Aborigines and Islanders Day Observance Committee celebrations in Perth, Western Australia. METHODS: People who visited the Dental Health Services display stall at the event completed a questionnaire on dental service use, perceived need and self-rated oral health domains. RESULTS: Participants provided 145 usable questionnaires; 75% of the sample identified themselves as Aboriginal/Torres Strait Islander of whom 45% had a dental visit less than 12 months ago; 33% had a check-up visit and 25% rated their oral health as fair or poor. CONCLUSIONS: More Aboriginal respondents reported lower frequency of service use and asymptomatic visiting compared with non-Aboriginal respondents. PMID- 26853204 TI - Tikanga Maori (Maori Customary Practices) in Oral Health Research. AB - Early childhood caries is a global health issue for Indigenous populations. The study, "Reducing disease burden and health inequalities arising from chronic dental disease among Indigenous children: an early childhood caries intervention," is being conducted in Australia, Canada, and Aotearoa/New Zealand. OBJECTIVE: To conduct the research in New Zealand using a kaupapa Maori (Maori philosophy) approach. METHODS: This is a mixed-method study incorporating quantitative and qualitative data whilst acknowledging Maori cultural practices by the utilization of Te Whare Tapa Wha, a model for Maori health and well-being. RESULTS: This paper describes the application of the four dimensions of this model, (spiritual, mental, physical and family dimensions) within the research activity. CONCLUSION: Health research projects that are undertaken with Indigenous populations must ensure that the research process embraces Indigenous cultural practices. In Aotearoa/New Zealand Maori leadership over the research process ensures meaningful and beneficial outcomes for the Maori Indigenous population. PMID- 26853205 TI - Changes in Area-level Socioeconomic Status and Oral Health of Indigenous Australian Children. AB - OBJECTIVE: Dental diseases have shown to be influenced by area-level socioeconomic status. This study aims to assess the effects of change in area level SES on the oral health of Australian Indigenous children. METHODS: Data were collected from a national surveillance survey for children's dental health at two points of time (2000-2002/2007-2010). The study examines caries experienced by area-level SES and whether changes in area-level SES (stable-high, upwardly-mobile, downwardly-mobile and stable low) affects caries experience. RESULTS: Dental caries in both the deciduous and permanent dentition increased significantly among Indigenous children during the study period. In stable low SES areas, the experience of decayed, missing and overall dmft/DMFT in both dentitions was highest compared with other groups at both Time 1(2.15 vs 1.61, 1.77, 1.87 and 0.86 vs 0.55, 0.67, 0.70 respectively) and Time 2 (3.23 vs 2.08, 2.17, 2.02 and 1.49 vs 1.18, 1.21 respectively). CONCLUSION: A change in area level SES was associated with experience of dental disease among Indigenous Australian children. PMID- 26853206 TI - Fidelity of Motivational Interviewing in an Early Childhood Caries Intervention Involving Indigenous Australian Mothers. AB - OBJECTIVES: This paper assessed the fidelity of an early childhood caries MI intervention among Aboriginal mothers in South Australia. METHODS: Four MI trained staff delivered the intervention and all interviews were recorded. A randomly selected subset (n = 164, 41.2%) were tested for MI fidelity using the Motivational Interviewing Treatment Integrity (MITI) code 3.1.1. A further randomly selected 20 taped sessions were additionally scored by an external expert to assess external reliability. RESULTS: Mean scores for evocation, collaboration, autonomy/support, direction and empathy ranged from 3.5 (95% CI 3.4-3.7) to 4.1 (95% CI 4.0-4.2). The mean global score was 3.8 (95% 3.7-3.9). The Reflection:Question ratio was 0.9 (95% CI 0.8-1.0), % Open-ended Questions was 54.9 (95% CI 50.0-59.8), % Complex Reflections was 54.0 (95% CI 50.5-57.5) and % MI-adherent statements was 95.0 (95% CI 92.0-98.0). Inter-assessor reliability was high. CONCLUSIONS: Beginner to expert competency in fidelity to the MI model was observed. PMID- 26853207 TI - Oral Health Status of the Veddas--Sri Lankan Indigenous People. AB - Sri Lanka's Veddas/Vanniya-laeto, are a small Indigenous group today with little information on their oral health status. This report is to provide an overview on oral health status of Veddas. Oral health status was recorded by the principal investigator after obtaining consent, using World Health Organization criteria, at an initial screening point before sending the person for any necessary treatment. Total participants were 194: 78% were males>35 years. Mean decayed, missing, filled teeth was 0.9 and 3% had pockets <3.5mm. Three had oral potentially malignant disorders (OPMDs), while three were treated for oral cancer. While the prevalence of dental caries and periodontal conditions was low, oral cancer and OPMDs is a serious concern. The Veddas have a culturally specific health system based on herbal medicinal knowledge. Thus, it is challenging to introduce and implement a preventive and curative oral health care system that would be culturally acceptable to this community. PMID- 26853208 TI - Factors Relating to Access to Dental Care for Indigenous South Australians. AB - OBJECTIVE: To explore and document self-reported factors contributing to Indigenous Australians' attendance and non-attendance at South Australian public dental clinics. METHODS: Semi-structured interviews were conducted with people (18 males and 26 females) referred for oral care through the Aboriginal Liaison Program of the South Australian Dental Service. Thematic analysis was performed on 44 transcribed conversations and a conceptual model developed. RESULTS: Persons completing all recommended treatment reported high self-efficacy, health literacy, social cohesion and previous use of dental services and presence of a health advocate. Those completing some recommended treatment reported achieving desired oral health outcome of relief of pain or system-level barriers to completion. Those reporting accessing no dental treatment in contrast reported varied and complex barriers to dental care. CONCLUSION AND IMPLICATIONS: Differences in both individual and health service-related factors were evident. Individual-level factors related to health literacy, self-efficacy, and social control. Service factors related to availability of an advocate, service delivery, and culture. Practical service-level changes may alleviate the effects of individual-level factors. PMID- 26853209 TI - Inequalities in Tooth Decay in Australian Children by Neighbourhood Characteristics and Indigenous Status. AB - OBJECTIVE: Tooth decay is related to poverty, measured at individual and neighbourhood levels. It is however uncertain if living in an advantaged neighbourhood reduces tooth decay similarly in Australian Indigenous and non Indigenous children. METHODS: This study describes tooth decay by neighbourhood characteristics and Indigenous status, and examines inequalities by Indigenous status. RESULTS: In deciduous dentition the percentage of children with tooth decay and untreated decay decreased on average 26% and 20% respectively in the non-Indigenous sample from poor to affluent neighbourhoods. In Indigenous children tooth decay and untreated decay decreased on average 6% and 8%, respectively, from poor to affluent neighbourhoods. CONCLUSION: While all children from affluent areas had less tooth decay, the gap between non-Indigenous and Indigenous children remained significant across neighbourhood characteristics. This suggests that both universal and targeted prevention programs should be considered for all Indigenous children irrespective of where they live. PMID- 26853210 TI - Racism and Oral Health Outcomes among Pregnant Canadian Aboriginal Women. AB - This study assessed links between racism and oral health outcomes among pregnant Canadian Aboriginal women. Baseline data were analyzed for 541 First Nations (94.6%) and Metis (5.4%) women in an early childhood caries preventive trial conducted in urban and on-reserve communities in Ontario and Manitoba. One-third of participants experienced racism in the past year determined by the Measure of Indigenous Racism Experience. In logistic regressions, outcomes significantly associated with incidents of racism included: wearing dentures, off-reserve dental care, asked to pay for dental services, perceived need for preventive care, flossing more than once daily, having fewer than 21 natural teeth, fear of going to dentist, never received orthodontic treatment and perceived impact of oral conditions on quality of life. In the context of dental care, racism experienced by Aboriginal women can be a barrier to accessing services. Programs and policies should address racism's insidious effects on both mothers' and children's oral health outcomes. PMID- 26853211 TI - Oral Health Impact among Rural-dwelling Indigenous Adults in South Australia. AB - AIMS: The aim of this study was to describe the impact of oral health conditions among a convenience sample of Indigenous Australian adults and compare findings with nationally representative data. METHODS: Data were obtained from the Indigenous Oral Health Literacy Project (IOHLP) based in South Australia. Nationally representative data were obtained from the National Survey of Adult Oral Health (NSAOH). The impact of oral disease was measured using the shortened form of the oral health impact profile, OHIP-14. All data were standardised by age group and sex utilising Census data. RESULTS: For each OHIP-14 measure the impact was greater for IOHLP participants. There was considerable variation in the degree of difference between IOHLP and NSAOH participants for individual OHIP 14 items. CONCLUSION: High levels of effects of oral health conditions were reported by rural-dwelling Indigenous adults. This may exacerbate the health and social disadvantage experienced by this marginalised group. PMID- 26853212 TI - Editorial. Special Issue Journal of Health Care for Poor and Underserved, Indigenous Oral Health. PMID- 26853213 TI - Accessing the Triplet State in Heavy-Atom-Free Perylene Diimides. AB - Previous studies of perylenediimides (PDIs) mostly utilized the lowest singlet excited state S1 . Generation of a triplet excited state (T1 ) in PDIs is important for applications ranging from photodynamic therapy to photovoltaics; however, it remains a formidable task. Herein, we developed a heavy-atom-free strategy to prompt the T1 <-S1 intersystem crossing (ISC) by introducing electron donating aryl (Ar) groups at the head positions of an electron-deficient perylenediimide (PDI) core. We found that the ISC efficiency increases from 8 to 54 % and then to 86 % by increasing the electron-donating ability of head substituted aryl groups from phenyl (p-PDI) to methoxyphenyl (MeO-PDI) and then to methylthioxyphenyl (MeS-PDI). By enhancing the intramolecular charge-transfer (ICT) interaction from p-PDI to MeO-PDI, and then to MeS-PDI, singlet oxygen generation via energy-transfer reactions from T1 of PDIs to (3)O2 was demonstrated with the highest yield of up to 80 %. These results provide guidelines for developing new triplet-generating PDIs and related rylene diimides for optoelectronic applications. PMID- 26853214 TI - Barriers to utilisation of cervical cancer screening in Sub Sahara Africa: a systematic review. AB - BACKGROUND: Cervical cancer is the commonest cause of cancer-related death in Sub Sahara Africa (SSA). Both primary and secondary preventive services are available but utilisation remain low. This systematic review aims to summarise reported barriers preventing women from utilising cervical cancer screening services in SSA. METHOD: Electronic searches on MEDLINE, EMBASE, PsycINFO, BIOSIS preview, Global Health, PubMed, Cochrane library, CINAHL, ISI Web of Knowledge and Google scholar and quality assessment of the included studies were performed. A meta analysis was applied to identify major themes. RESULTS: Eight studies exploring reasons women did not utilise cervical cancer screening were included. Women in SSA reported similar barriers despite cultural and language diversity in the region. Women reported fear of screening procedure and negative outcome, low level of awareness of services, embarrassment and possible violation of privacy, lack of spousal support, societal stigmatisation, cost of accessing services and health service factors like proximity to facility, facility navigation, waiting time and health care personnel attitude. CONCLUSION: Strategies for improving uptake and utilisation of cervical screening in SSA should focus on improving cervical health education, addressing cultural beliefs and practices and improving spousal support and empowering women, as well as addressing physical access problem, costs and improving staff attitude. PMID- 26853215 TI - Persistently raised and falling hCG at 6 months no longer a criterion for post molar gestational trophoblastic neoplasia? PMID- 26853216 TI - Salmonella Vaccination in Pigs: A Review. AB - The control of Salmonella enterica in pig production is necessary for both public and animal health. The persistent and frequently asymptomatic nature of porcine Salmonella infection and the organism's abilities to colonize other animal species and to survive in the environment mean that effective control generally requires multiple measures. Vaccination is one such measure, and the present review considers its role and its future, drawing on studies in pigs from the 1950s to the present day. Once established in the body as an intracellular infectious agent, Salmonella can evade humoral immunity, which goes some way to explaining the often disappointing performance of inactivated Salmonella vaccines. More recent approaches, using mucosal presentation of antigens, live vaccines and adjuvants to enhance cell-mediated immunity, have met with more success. Vaccination strategies that involve stimulating both passive immunity from the dam plus active immunity in offspring appear to be most efficacious, although either approach alone can yield significant control of Salmonella. Problems that remain include relatively poor control of Salmonella serovars that are dissimilar to the vaccine antigen mix, and difficulties in measuring and predicting the performance of candidate vaccines in ways that are highly relevant to their likely use in commercial production. PMID- 26853217 TI - Genomewide association study of immune traits in chicken F2 resource population. AB - Immune traits play pivotal roles in animal immune capacity development and disease resistance. Single nucleotide polymorphisms (SNPs) are common forms of genetic variations among individuals, which are thought to account for the majority of inherited phenotypic variations. In this study, we performed genomewide association, using the Illumina 60K SNP BeadChip studies to detect molecular markers and candidate genes associated with immune traits in an F2 population. Sixteen immune traits were measured. We identified 85 significant SNPs (p < 2.98 * 10(-6) ) with 5% as the genomewide significance threshold, 380 SNPs of suggestive significance (p < 5.96 * 10(-5) ) from simple model (general linear model, GLM) and 15 SNPs of suggestive significance (p < 5.96 * 10(-5) ) from the compressed mixed linear model (MLM), which were also found in GLM (six significant SNPs and seven suggestive SNPs). Three significant SNPs (GGaluGA151406, Gga_rs14554319 and Gga_rs13593979) and candidate genes (LYRM4 and KTN1) were found to be associated with avian influenza antibody titres, and the first two SNPs are from the results of two-model analysis. For the immune organs, through the analysis of GLM, 19 SNPs were found to be significantly associated with the thymus weight, 61 SNPs were significantly associated with the bursa of Fabricius weight, six of which were located within a 34-Mb region (125 846 474 159 649 698 bp) on chicken chromosome 1 (GGA1). A candidate region relevant to haematological traits from GLM was found in GGA4 and 9 loci were located on it. Three loci (GGaluGA348521, Gga_rs16098446 and GGaluGA348518) within 179 kb (16 286 868-16 466 134 bp) on GGAZ from GLM provided evidence that this genomic segment may be relevant to red blood cell volume distribution width (RDW). Our study provides a list of significant SNPs and candidate genes that will be valuable information for unveiling the underlying molecular mechanism of immune regulation. PMID- 26853219 TI - Development of a cross-disciplinary continuous insulin infusion protocol for non critically ill patients in a French university hospital. AB - RATIONALE, AIMS AND OBJECTIVES: In non-critically ill patients, the use of an insulin syringe pump allows the management of temporary situations during which other therapies cannot be used (failure of subcutaneous injections, awaiting advice from the diabetes team, emergency situations, prolonged corticosteroid therapy, initiation of an artificial nutrition, need for a fasting status, etc.). To manage the risks related to this "never event", the use of a standard validated protocol for insulin administration and monitoring is an essential prerequisite. To this end, a multidisciplinary approach is recommended. METHOD: With the support of our subcommission "Endocrinology-Diabetology", we proceeded with a "step-by-step process" to create such a standardized protocol: (1) review of all existing protocols in our hospital; (2) overview of the literature data concerning insulin infusion protocols developed by multidisciplinary teams in France and abroad; (3) development of a standardized protocol for non-intensive care unit patients, respecting the current recommendations and adapting it to the working habits of health teams; and (4) validation of the protocol RESULTS: Two protocols based on the same structure but adapted to the health status of the patient have been developed. The protocols are divided in to three parts: (1) golden rules to make the use of the protocol appropriate and safe; (2) the algorithm (a double entry table) corresponding to a dynamic adaptation of insulin doses, clearly defining the target and the 'at risk situations'; and (3) practical aspects of the protocol: preparation of the syringe, treatment initiation and traceability. The protocols have been validated by the institution. CONCLUSION: Our standardized insulin infusion protocol is simple, easy to implement, safe and is likely to be applicable in diverse care units. However, the efficiency, safety and the workability of our protocols have to be clinically evaluated. PMID- 26853218 TI - Spectral-Domain Optical Coherence Tomography as a Potential Biomarker in Huntington's Disease. AB - BACKGROUND: Spectral-domain optical coherence tomography has been used in several neurological conditions, and peripapillary and macular measurements have been proposed as potential biomarkers in these disorders. The aim of this study was to investigate retinal and choroidal changes in Huntington's disease and to evaluate any potential correlation with the stage of the disease. METHODS: A cross sectional observational study compared patients with Huntington's disease and controls. Patients were evaluated using the Unified Huntington's Disease Rating Scale. Spectral-domain optical coherence tomography with enhanced depth imaging was used, and peripapillary choroidal and retinal nerve fiber layer thickness and macular retinal and choroidal thickness were evaluated. RESULTS: Fifteen eyes of 8 patients and 16 eyes of 8 sex-, age-, and mean refractive error-matched healthy controls were included. Average (231.3 +/- 52.8 vs 296.2 +/- 57.1, P = 0.033), central (341.8 +/- 70.5 vs 252.0 +/- 57.9, P = 0.015), and inferior (225.3 +/- 57.9 vs 313.8 +/- 55.2, P = 0.007) macular choroidal thickness were significantly reduced in patients, in comparison with controls. No differences were observed in macular retina or peripapillary retinal and choroidal measurements. However, there was a negative correlation between Total Motor Score of the Unified Huntington's Disease Rating Scale and average (r(2) = 0.585, P = 0.027), superior (r(2) = 0.653, P = 0.015), nasal (r(2) = 0.642, P = 0.017), and inferior (r(2) = 0.574, P = 0.029) macular retinal thickness. CONCLUSIONS: Our results suggest that both the choroidal and retinal macula are altered in Huntington's disease and may become useful biomarkers for monitoring neurodegeneration in this disease. The involvement of the choroid may also support the recent findings of vascular involvement in Huntington's disease. PMID- 26853220 TI - Cytokine-dependent activation of JAK-STAT pathway in Saccharomyces cerevisiae. AB - Protein phosphorylation is an important post-translational modification for intracellular signaling molecules, mostly found in serine and threonine residues. Tyrosine phosphorylations are very few events (less than 0.1% to phosphorylated serine/threonine residues), but capable of governing cell fate decisions involved in proliferation, differentiation, apoptosis, and oncogenic transformation. Hence, it is important for drug discovery and system biology to measure the intracellular level of phosphotyrosine. Although mammalian cells have been conventionally utilized for this purpose, accurate determination of phosphotyrosine level often suffers from high background due to the unexpected crosstalk among endogenous signaling molecules. This situation led us firstly to establish the ligand-induced activation of homomeric receptor tyrosine kinase (i.e., epidermal growth factor receptor) in Saccharomyces cerevisiae, a lower eukaryote possessing organelles similar to higher eukaryote but not showing substantial level of tyrosine kinase activity. In this study, we expressed heteromeric receptor tyrosine kinase (i.e., a complex of interleukin-5 receptor (IL5R) alpha chain, common beta chain, and JAK2 tyrosine kinase) in yeast. When coexpressed with a cell wall-anchored form of IL5, the yeast exerted the autophosphorylation of JAK2, followed by the phosphorylation of transcription factor STAT5a and subsequent nuclear accumulation of phosphorylated STAT5a. Taken together, yeast could be an ideal host for sensitive detection of phosphotyrosine generated by a wide variety of tyrosine kinases. Biotechnol. Bioeng. 2016;113: 1796-1804. (c) 2016 Wiley Periodicals, Inc. PMID- 26853221 TI - Late-onset distal myopathy of the upper limbs due to P.Ile151Val mutation in the valosin-containing protein. PMID- 26853222 TI - In response to Inferior peduncle lesion presenting with bilaterally impaired vestibular responses to horizontal and posterior head impulses. PMID- 26853223 TI - When silence is noise: infantile-onset Barth syndrome caused by a synonymous substitution affecting TAZ gene transcription. AB - Barth syndrome (BTHS) is an X-linked inborn error of metabolism which affects males. The main manifestations are cardiomyopathy, myopathy, hypotonia, growth delay, intermittent neutropenia and 3-methylglutaconic aciduria. Diagnosis is confirmed by mutational analysis of the TAZ gene and biochemical dosage of the monolysocardiolipin/tetralinoleoyl cardiolipin (MLCL:L4-CL) ratio. We report a 6 year-old boy who presented with severe hypoglycemia, lactic acidosis and severe dilated cardiomyopathy soon after birth. The MLCL:L4-CL ratio confirmed BTHS (3.90 on patient's fibroblast, normal: 0-0.3). Subsequent sequencing of the TAZ gene revealed only the new synonymous variant NM_000116.3 (TAZ):c.348C>T p.(Gly116Gly), which did not appear to affect the protein sequence. In silico prediction analysis suggested the new c.348C>T nucleotide change could alter the TAZ mRNA splicing processing. We analyzed TAZ mRNAs in the patient's fibroblasts and found an abnormal skipping of 24 bases (NM_000116.3:c.346_371), with the consequent ablation of 8 amino acid residues in the tafazzin protein (NP_000107.1:p.Lys117_Gly124del). Molecular analysis of at risk female family members identified the patient's sister and mother as heterozygous carriers. Apparently harmless synonymous variants in the TAZ gene can damage gene expression. Such findings widen our knowledge of molecular heterogeneity in BTHS. PMID- 26853224 TI - Health System Consolidation and Diabetes Care Performance at Ambulatory Clinics. AB - OBJECTIVE: We addressed two questions regarding health system consolidation through the acquisition of ambulatory clinics: (1) Was increasing health system size associated with improved diabetes care performance and (2) Did the diabetes care performance of acquired clinics improve postacquisition? DATA SOURCES/STUDY SETTING: Six hundred sixty-one ambulatory clinics in Minnesota and bordering states that reported performance data from 2007 to 2013. STUDY DESIGN: We employed fixed effects regression to determine if increased health system size and being acquired improved clinics' performance. Using our regression results, we estimated the average effect of consolidation on the performance of clinics that were acquired during our study. DATA COLLECTION/EXTRACTION METHODS: Publicly reported performance data obtained from Minnesota Community Measurement. PRINCIPAL FINDINGS: Acquired clinics experienced performance improvements starting in their third year postacquisition. By their fifth year postacquisition, acquired clinics had 3.6 percentage points (95 percent confidence interval: 2.0, 5.1) higher performance than if they had never been acquired. Increasing health system size was associated with slight performance improvements at the end of the study. CONCLUSIONS: Health systems modestly improved the diabetes care performance of their acquired clinics; however, we found little evidence that systems experienced large, system-wide performance gains by increasing their size. PMID- 26853225 TI - Levels of Hair Ethyl Glucuronide in Patients with Decreased Kidney Function: Possibility of Misclassification of Social Drinkers. AB - BACKGROUND: The use of hair ethyl glucuronide (EtG) levels as a biomarker for chronic high intake of ethanol (EtOH) is increasing, and misclassification of alcohol consumption may have large implications for the patient. The aim of this study was to compare levels of hair EtG in patients with reduced kidney function to levels seen in a comparable control group and to investigate whether the hair EtG levels among kidney failure patients who are social drinkers may lead to a false-positive diagnosis of heavy drinking. METHODS: A total of 41 patients with reduced kidney function and 42 healthy volunteers were included in the study. Both patients and the healthy volunteers reported moderate alcohol intake. The levels of EtG in hair (corrected for estimated daily intake of EtOH [EDI]) were compared between the 2 groups. RESULTS: There was no significant difference between the groups regarding EDI. Despite this, there were significant higher levels of hair EtG (corrected for EDI) in the patient group compared to the control group (p < 0.001). Eight subjects (20%) in the patient group showed EtG levels in hair above 30 pg/mg, in contrast to no subjects among healthy volunteers (p = 0.002). In the patient group, there was significant correlation between levels of EtG in hair and both estimated glomerulus filtration rate and serum creatinine levels. CONCLUSIONS: This study documents an increased risk of obtaining a false-positive diagnosis of heavy drinking among renal disease patients who are social drinkers. Interpretation of EtG levels in hair among patients with reduced kidney function must be performed with caution. PMID- 26853226 TI - delta-Methyl Branching in the Side Chain Makes the Difference: Access to Room Temperature Discotics. AB - Although discotic liquid crystals are attractive functional materials, their use in electronic devices is often restricted by high melting and clearing points. Among the promising candidates for applications are [15]crown-5 ether-based liquid crystals with peripheral n-alkoxy side chains, which, however, still have melting points above room temperature. To overcome this problem, a series of o terphenyl and triphenylene [15]crown-5 ether derivatives was prepared in which delta-methyl-branched alkoxy side chains of varying lengths substitute the peripheral linear alkoxy chains. The mesomorphic properties of the novel crown ethers were studied by differential scanning calorimetry, polarizing optical microscopy, and X-ray diffraction. delta-Methyl branching indeed lowers melting points resulting in room-temperature hexagonal columnar mesophases. The mesophase widths, which ranged from 87 to 30 K for o-terphenyls, significantly increased to 106-147 K for the triphenylenes depending on the chain lengths, revealing the beneficial effect of a flat mesogen, due to improved pi-pi interactions. PMID- 26853227 TI - A one-step automated synthesis of the dopamine transporter ligand [(18)F]FECNT from the chlorinated precursor. AB - The use of [(18)F]labelled nortropane derivative 2beta-carbomethoxy-3beta-(4 chlorophenyl)-8-(2-fluoroethyl)-nortropane (FECNT) as a dopamine transporter ligand for PET imaging is dependent on efficient radiosynthesis method. Herein, the automated synthesis of [(18)F]FECNT from its chlorinated precursor in commercially available SynChrom [(18)F] R&D module has been developed. The synthesis unit was readily configured for the one-step synthesis from corresponding chlorinated precursor. The radiolabeling process involved a classical [(18)F]fluoride nucleophilic substitution performed at 110 degrees C for 12 min and finally HPLC and SPE purification. Crude [(18)F]FECNT was obtained with a radiolabeling yield of 59 +/- 12% (n = 5). The average uncorrected amount of [(18)F]FECNT in the final formulated dose was 2.0 +/- 0.5 GBq (32 +/- 7% overall decay-corrected yields) obtained with radiochemical purity over 99% and specific activity of 55 GBq/umol. The total duration of the procedure was 80-90 min. An automated radiosynthesis of [(18)F]FECNT with high radiochemical purity may provide a simple and robust method of radiopharmaceutical preparation for routine clinical applications. PMID- 26853228 TI - When a general morphology allows many habitat uses. AB - During the last decades the study of functional morphology received more attention incorporating more detailed data corresponding to the internal anatomy that together contribute for a better understanding of the functional basis in locomotion. Here we focus on 2 lizard families, Tropiduridae and Liolaemidae, and use information related to muscle-tendinous and external morphology traits of hind legs. We investigate whether the value of the traits analyzed tend to exhibit a reduced phenotypic variation produced by stabilizing selection, and whether species showing specialization in their habitat use will also exhibit special morphological features related to it. As a result, we identified that evolution of hind limb traits is mainly explained by the Ornstein-Uhlenbeck model, suggesting stabilizing selection. Liolaemids and tropidurids show clear ecomorphological trends in the variables considered, with sand lizards presenting the most specialized morphological traits. Some ecomorphological trends differ between the 2 lineages, and traits of internal morphology tend to be more flexible than those of external morphology, restricting the ability to identify ecomorphs shared between these 2 lineages. Conservative traits of external morphology likely explain such restriction, as ecomorphs have been historically defined in other lizard clades based on variation of external morphology. PMID- 26853229 TI - Phenotypic and molecular characterization of focal dermal hypoplasia in 18 individuals. AB - Focal dermal hypoplasia, or Goltz syndrome, is a highly variable X-linked dominant disorder with abnormalities in ectoderm and mesoderm derived tissues. Classic clinical features include patchy hypoplastic skin, split hand/foot deformities, and ocular malformations. We aimed to refine the understanding of the phenotypic spectrum and natural history of this disorder and now present multi-disciplinary clinical description and medical history review for 18 patients with focal dermal hypoplasia. All disease characteristics were analyzed and compiled in aggregate to aid in development of clinical diagnostic criteria. Medical history data unexpectedly revealed that the majority of patients (87%) had undergone tonsillectomy for obstructive sleep apnea, which exposed an important co-morbidity that is not well described in the literature, but managing physicians should be made aware of. Fifteen of the 18 patients underwent molecular sequencing of PORCN to detect heterozygous or mosaic mutations. Where no mutation was detected, we performed exon-targeted chromosomal microarray to evaluate for large deletions of the PORCN gene region. We detected a pathogenic genotype in 14 of 15 patients, including one novel chromosomal deletion and four novel PORCN sequence variants. Here, we provide phenotypic summary analysis of 18 patients with focal dermal hypoplasia and propose clinical diagnostic criteria. PMID- 26853230 TI - Retreatment with sofosbuvir and simeprevir of patients with hepatitis C virus genotype 1 or 4 who previously failed a daclatasvir-containing regimen. AB - Failure to achieve sustained virological response (SVR) with hepatitis C virus (HCV) direct-acting antiviral-based regimens is commonly associated with emergence of resistance-associated variants (RAVs). To avoid cross-resistance, recent guidelines recommend that patients who have failed on nonstructural protein 5A (NS5A) inhibitors should be retreated with sofosbuvir (SOF; NS5B inhibitor) combined with simeprevir (SIM; protease inhibitor [PI]); however, supporting evidence is lacking. This "real-world" study comprised patients who had failed to achieve SVR on previous NS5A-based therapy with daclatasvir (DCV) plus pegylated interferon (Peg-IFN) and ribavirin (RBV), with (n = 3) or without (n = 13) asunaprevir (ASV; PI). All 16 patients were retreated for 12 weeks with SOF plus SIM, without RBV. Antiviral efficacy was evaluated using the primary endpoint of SVR12 (SVR 12 weeks post-treatment); on-treatment response was also assessed. Patients (N = 16; 13 male; mean age: 54 years [range, 43-73]) were chronically infected with HCV genotype (GT) 1 (1a, n = 11; 1b, n = 3) or 4 (n = 2); they had advanced fibrosis or compensated cirrhosis (FibroScan, 9.6-70 kPa; cirrhosis, n = 9); median baseline HCV-RNA level was 1.38 * 10(6) IU/mL. No patient discontinued treatment because of adverse events or virological failure. All patients achieved HCV RNA below lower limit of quantification (<12 IU/mL) by end of treatment (EOT) and 10 of 16 had a rapid response (week 4). SVR12 was achieved by 14 of 16 patients; the remaining 2 relapsed by 4 weeks post-EOT (both were GT 1a infected with cirrhosis; 1 had previously failed DCV-ASV plus Peg-IFN and RBV). Presence of SIM RAVs/polymorphisms (R155K and Q80K) at study baseline did not predict retreatment failure. CONCLUSION: Our findings support the concept of retreating NS5A inhibitor failures with SOF combined with SIM. However, the most difficult-to-cure patients may need more than 12 weeks of treatment and/or the addition of RBV. (Hepatology 2016;63:1809-1816). PMID- 26853231 TI - Hypersensitivity toward bacterial stimuli in patients with age-related macular degeneration. AB - Although the pathogenesis of age-related macular degeneration (AMD) is unclear, genetic screening has revealed that polymorphisms in the complement system may be associated with AMD development. Production of autoantibodies was also found in AMD patients. In this study, we analyzed the antibody response in AMD patients. We found that purified B cells from AMD patients tended to respond to lower concentrations of bacterial antigen stimulation, and produced higher amounts of antibodies, especially in IgM and IgA secretions. When examining clinical symptoms, patients with more severe wet-form AMD tended to exhibit higher sensitivity to bacterial antigens and secreted more IgM and IgA antibodies than those with less severe dry-form cases. In conclusion, our study discovered an altered B-cell antibody production in response to bacterial antigens in AMD patients, which potentially contributes to AMD pathogenesis. PMID- 26853232 TI - Lateral Sinus Thrombosis: The Importance of the Unaffected Sinus. AB - BACKGROUND AND PURPOSE: Intracranial hypertension develops in only some patients with lateral sinus thrombosis (LST), for reasons that are unclear. The purpose of this study was to evaluate a possible association between patency of the unaffected sinus and clinical presentation of unilateral LST. METHODS: A computerized search identified patients with LST, hospitalized in Soroka Medical Center. Patients with signs of increased intracranial pressure (iICP) and those with normal intracranial pressure (nICP) were compared. CT venography or MR venography confirmed the diagnosis, located the thrombosis, and determined the dominant lateral sinus (LS). Diameters of the right and left LSs (the occluded and unaffected) were compared to the diameter of the distal superior sagittal sinus (SSS). RESULTS: Of the 50 patients identified, 30 had iICP and 20 nICP. The dominant LS was the right one in 39 (78%) and the left one in 8 (16%); 3 (6%) had equal LS dominance. The dominant sinus was affected in 32 (70%) and the non dominant in 15 (30%) patients. iICP was detected in 28/32 (81%) of patients with the dominant side affected, and 3/15 (20%) of those with non-dominant thrombotic sinus (P = .002). The unaffected sinus was narrower in iICP patients (size relative to SSS diameter = 43% in iICP vs. 86% in nICP [P = .0002]; size grading, according to Farb's method was 1.86 in the iICP vs. 3.57 in the nICP group [P = .0001]). CONCLUSIONS: Thrombosis was more common in the dominant LS. Unaffected LS patency appears to be associated with the development of increased ICP. PMID- 26853233 TI - Fitting recommendations and clinical benefit associated with use of the NAL-NL2 hearing-aid prescription in Nucleus cochlear implant recipients. AB - OBJECTIVE: For a group of cochlear implant recipients, who use hearing aids in the contralateral ear, the benefit of NAL-NL2 relative to a recipients' own prescription was assessed. Whether there was a preferred frequency response and/or gain deviation from NAL-NL2 was then investigated. DESIGN: Speech recognition and self-reported ratings of benefit were examined for the recipients' own prescription compared to the NAL-NL2 prescription, in the bimodal and hearing-aid alone conditions. Paired-comparison of hearing-aid frequency response was conducted with default NAL-NL2 and two variants, a low frequency boost or cut. Using a loudness balancing procedure, the hearing-aid gain required to achieve equal loudness between the devices was measured. STUDY SAMPLE: Sixteen adults with post-lingual hearing loss. RESULTS: A 22% increase in group median word score in quiet with use of NAL-NL2 in the hearing-aid alone condition. In the bimodal condition there was no improvement with NAL-NL2. Default NAL-NL2 frequency response was preferred by 67% of participants. For 56% of participants, the preferred gain to achieve loudness balance across bimodal devices was within 5-dB of prescribed values. CONCLUSIONS: The NAL-NL2 prescription provides a high level of clinical performance, and an acceptable frequency response and gain for most participants. PMID- 26853234 TI - Innovative applications of food-related emulsions. AB - Research on oxidative stability of multiple emulsions is very scarce. Given that this is a relevant topic that must be ascertained before the successful application of multiple emulsions in foods (especially when a combination of highly unsaturated oils is used as a lipid phase), this review mainly focuses on various aspects of the multiple emulsions. Fat replacement in meat products using emulsions is critically discussed along with innovative applications of natural antioxidants in food-based emulsions and multiple emulsions based on bioactive compounds/encapsulation as well as confectionery products. PMID- 26853235 TI - How can we improve antibiotic prescribing in primary care? AB - Antibiotic stewardship is a necessity given the worldwide antimicrobial resistance crisis. Outpatient antibiotic use represents around 90% of total antibiotic use, with more than half of these prescriptions being either unnecessary or inappropriate. Efforts to improve antibiotic prescribing need to incorporate two complementary strategies: changing healthcare professionals' behaviour, and modifying the healthcare system. In this review, we present a broad perspective on antibiotic stewardship in primary care in high and high middle income country settings, focussing on studies published in the last five years. We present the limitations of available literature, discuss perspectives, and provide suggestions for where future work should be concentrated. PMID- 26853237 TI - Effects of a 6-week Nordic walking training on changes in 25(OH)D blood concentration in women aged over 55. AB - BACKGROUND: Nordic walking is a form of physical activity recommended for people of all ages and it is used in disease prevention and health promotion. The study was aimed to determine if and in what ways a six-week Nordic walking training program in late autumn may affect 25(OH)D concentration in postmenopausal overweight women. METHODS: Two series of measurements were carried out in a group of 17 women aged 57+/-4.20 years with low physical activity level. The first series encompassed a 6-week Nordic walking training program at the intensity of 60-70% VO2max. Before and after the training program body composition was determined with a densitometer, and biochemical indices were measured in blood samples drawn at rest. After a year a second series of measurements at rest was carried out to determine whether changes in the vitamin D (25(OH)D) blood level were season-induced or modified by physical activity. RESULTS: The Nordic walking training program contributed to a significant reduction of body mass, percentage fat volume and BMI in the examined women. The mean 25(OH)D concentration in the examined women significantly decreased after 6 weeks of training. No similar vitamin D level changes were observed in the II measurement series. CONCLUSIONS: A six-week Nordic walking training program in late autumn contributed to the lowering of 25(OH)D blood concentration in women after 55 years of age. The decreased 25(OH)D concentration may have been a result of reduced dermal biosynthesis of vitamin D or due to vitamin D contribution to muscle metabolism. This is an indication that vitamin D3 supplementation should be recommended in periods of intense physical activity during months with little insolation, especially to overweight postmenopausal women. PMID- 26853236 TI - Symptoms of Knee Instability as Risk Factors for Recurrent Falls. AB - OBJECTIVE: Whether knee instability contributes to the increased risk of falls and fractures observed in persons with knee osteoarthritis (OA) has not been studied. We examined the association of knee buckling with the risk of falling and fall-related consequences in older adults with, or at high risk for, knee OA. METHODS: At the 60-month visit of the Multicenter Osteoarthritis Study, men and women ages 55-84 years were asked about knee buckling in the past 3 months and whether they fell when a knee buckled. Falls and fall-related injuries in the past 12 months and balance confidence were assessed at 60 and 84 months. Multivariate logistic regression was used to assess the association of knee buckling with falls and their consequences. RESULTS: A total of 1,842 subjects (59% women, mean +/- SD age 66.9 +/- 7.8 years, and body mass index 30.3 +/- 5.7) were included. At 60 months 16.8% reported buckling and at 84 months 14.1% had recurrent (>=2) falls. Bucklers at 60 months had a 1.6- to 2.5-fold greater odds of recurrent falls, fear of falling, and poor balance confidence at 84 months. Those who fell when a knee buckled at baseline had a 4.5-fold, 2-fold, and 3-fold increased odds 2 years later of recurrent falls, significant fall injuries, and fall injuries that limited activity, respectively, and were 4 times more likely to have poor balance confidence. CONCLUSION: Interventions that reduce knee buckling may help prevent falls, fall-related injuries, and adverse psychological consequences of falls in persons with knee OA. PMID- 26853238 TI - Changes in blood glucose among trained normoglycemic adults during a mini trampoline exercise session. AB - BACKGROUND: Blood glucose changes response during and after exercise are modulated by the postabsorptive state, intensity and duration of exercise, and the level of physical fitness as well. This study focused on the idea that high intensity interval exercise, as mini-trampoline class, can reduce blood glucose. Thus, we examined acute changes in blood glucose among trained normoglycemic adults during a mini-trampoline exercise session. METHODS: Twenty-four normoglycemic adult subjects were enrolled in the study. After physical assessment they were randomly assigned to either the experimental (N.=12) or the control group (N.=12). The experimental group performed a 50-minute session of moderate-to-high intensity (70 to 85% HRmax) exercise on a mini-trampoline commonly used in fitness classes. The control group did not perform any exercise, and all procedures were otherwise similar to the experimental group. Capillary blood glucose was measured before and every 15 minutes during the exercise session. The effects of exercise on blood glucose levels (group; time; and group interaction) were estimated using a generalized estimating equation (GEE) followed by Bonferroni's post-hoc Test (P<0.05). RESULTS: The experimental group showed a decrease in blood glucose levels from baseline (108.7 mg/dL): 26.1% reduction (15 min; P<0.001), 24.2% (30 min; P<0.001), and 15.7% (45 min; P<0.001). Compared to the control group, blood glucose levels in the experimental group were reduced by 18.8% (15 min; P<0.001), 14.3% (30 min; P<0.001) and 6.9% (45 min; P=0.025). CONCLUSIONS: The study results provide good evidence that a prescribed exercise program on a mini-trampoline can be used for reducing blood glucose levels and thus can potentially control blood glucose. PMID- 26853240 TI - Work efficiency in repeated sets of sprint interval exercise in cyclists. AB - BACKGROUND: While interval training is considered an effective modality for improving physical performance, there is a lack of data on the body's response to repeated sets of sprint exercise. The aim of this study was to assess changes in work efficiency during subsequent sets of sprint interval training in cyclists with different interval training experience. METHODS: The study involved 20 cyclists divided into two groups: those who had been performing interval training for at least one year (experienced [group E], N.=10) and those who had no experience with interval training (inexperienced [group IE], N.=10). All participants performed an interval training-based exercise test involving four sets of four 30-s repetitions of maximal ergometer cycling interspersed with 90 s of low-intensity recovery. Each set was followed by a period of active recovery (lasting 25-40 minutes). Work output, total oxygen uptake, work efficiency and post-exercise H+ concentration were collected in each set. RESULTS: Work output in group IE decreased by the second and third set (5% and 7.3%, respectively) while only in the fourth set (1.6%) in group E. Work efficiency in group E increased by 7.1%, 7.2%, and 5.1% in the second, third, and fourth set, respectively; total oxygen uptake decreased in the third set by 2.4%. H+ concentrations decreased in the second and subsequent sets in group IE whereas in the third and subsequent sets in group E. CONCLUSIONS: An improvement in work efficiency in subsequent sets of sprint interval training was found in cyclists with interval training experience. PMID- 26853239 TI - Branched-chain aminoacid supplementation attenuates a decrease in power-producing ability following acute strength training. AB - BACKGROUND: This study aimed to investigate the effects of branched-chain amino acid (BCAA) supplementation on recovery of power-producing ability following a strength training (ST) session. METHODS: Eleven resistance-trained males, performed baseline measures of a countermovement jump (CMJ) and a seated shot-put throw (SSPT). In a counterbalanced fashion, participants were provided with either 20-g of BCAA or a placebo. Each dose was divided into two equal quantities and consumed before and after a ST session consisting of various multi-joint barbell exercises. For both conditions, the CMJ and SSPT were repeated at 24-h post-ST, in addition participants attributed their perceived muscle soreness level via a 200-mm visual analogue scale. RESULTS: Following ST there were significant decrements in CMJ (baseline; 55.2+/-7.4-cm, BCAA; 52.8+/-5.9-cm placebo; 50.6+/-7.3-cm) and SSPT (baseline; 4.55+/-0.56-m, BCAA; 4.37+/-0.61-m, placebo; 4.22+/-0.64-m) for both conditions in comparison to baseline values (P<0.05). However, BCAA was shown to attenuate the decrements in CMJ and SSPT performance compared to placebo (P<0.05). Muscle soreness was significantly increased following ST for both conditions, however there were no differences in attributed values following BCAA and placebo ingestion. CONCLUSIONS: BCAA administered acutely before and following intensive ST attenuates a decrease in power-producing ability experienced by resistance-trained males. The apparent small but significant effects on functional power suggest that BCAA is an effective ergogenic aid for athletes who require augmented recovery of power producing ability following intensive ST. PMID- 26853242 TI - Variation potential propagation decreases heat-related damage of pea photosystem I by 2 different pathways. AB - Local burning is known to generate and propagate variation potential (VP) in plants. VP affects different physiological processes, including reducing heat related damage to photosystem I (PSI). We investigated mechanisms of the process. Photosynthesis parameters were measured with Dual-PAM-100 and GFS-3000. VP was induced by burning the first mature leaf and then waiting 5, 10, 15, or 20 min to initiate heating of the second mature leaf. Photosystems activities in the second leaf were investigated at 15 and 135 min after heating. In the absence of VP induction, when incubation in hot water (5 min) was used for heating the intact second leaf, PSI and PSII activities decreased after incubation at both exposure temperatures (45 degrees C and 50 degrees C). When local burning of the first leaf induced VP propagation into the second leaf, reduced photosynthesis (PSI) was observed. Arrival of VP in the second leaf prior to hot water incubation at 50 degrees C decreased heating-induced suppression of PSI activity when measured 15 and 135 min later. Dependence of PSI activity on the time interval (5, 10, 15, or 20 min) between VP induction and heating of the second leaf was dissimilar at 15 and 135 min. Heat-induced suppression of PSII activity in the second leaf was stimulated after VP induction. In contrast, the effect of VP on PSI and PSII damage was weak when leaf 2 was heated at 45 degrees C. VP-induced decrease of PSI activity suppression at 15 min after heating was correlated with stimulation of PSII activity suppression, but increase of PSI activity at 135 min after heating was not related to PSII activity. Thus, our results suggest the possibility of 2 different pathways of VP-induced decrease of heat-related PSI damage. PMID- 26853243 TI - Corrigendum: Ammonium sorption and ammonia inhibition of nitrite-oxidizing bacteria explain contrasting soil N2O production. PMID- 26853241 TI - Dopamine disruption increases negotiation for cooperative interactions in a fish. AB - Humans and other animals use previous experiences to make behavioural decisions, balancing the probabilities of receiving rewards or punishments with alternative actions. The dopaminergic system plays a key role in this assessment: for instance, a decrease in dopamine transmission, which is signalled by the failure of an expected reward, may elicit a distinct behavioural response. Here, we tested the effect of exogenously administered dopaminergic compounds on a cooperative vertebrate's decision-making process, in a natural setting. We show, in the Indo-Pacific bluestreak cleaner wrasse Labroides dimidiatus, that blocking dopamine receptors in the wild induces cleaners to initiate more interactions with and to provide greater amounts of physical contact to their client fish partners. This costly form of tactile stimulation using their fins is typically used to prolong interactions and to reconcile with clients after cheating. Interestingly, client jolt rate, a correlate of cheating by cleaners, remained unaffected. Thus, in low effective dopaminergic transmission conditions cleaners may renegotiate the occurrence and duration of the interaction with a costly offer. Our results provide first evidence for a prominent role of the dopaminergic system in decision-making in the context of cooperation in fish. PMID- 26853244 TI - Cardiac Valve Noise Reduction by Non-Drug Interventions Improves the Sleep Quality of Patients after Mechanical Cardiac Valve Implantation. AB - PURPOSE: To investigate the effects of non-drug interventions on the sleep quality of patients after mechanical cardiac valve implantation. METHODS: In this prospective, randomized, controlled trial, 64 patients scheduled for mechanical mitral valve replacement were recruited. Patients underwent cognitive behavioral therapy and wore noise cancelling earplugs and eye mask. Sleep quality was evaluated on the 4th after admission and the 5th days after operation. The primary outcome was the total sleep quality score differences between the 4th day after admission and the 5th day after operation. RESULTS: All patients had been suffering from poor sleep quality for a month before admission. There was no difference between both groups on the 4th day after admission. Overall sleep quality in the intervention group was better than in the control group on the 5th day after operation. The subjective sleep quality of the patients in each group was significantly lower on the 5th day after the operation than on the 4th day after admission (P <0.05). CONCLUSION: Non-drug intervention could improve the sleep quality of patients after mechanical cardiac valve implantation and help the postoperative recovery of the patients. ( TRIAL REGISTRATION: ChiCTR-TRC 14004405, 21 March 2014.). PMID- 26853245 TI - Pulmonary Myofibroblastic Tumour Involving the Pericardium and Left Atrium in an 18 Month Infant. AB - Inflammatory myofibroblastic tumor (IMT) is the most frequent primary lung tumor in children and it may be locally aggressive. The management of a locally advanced pulmonary IMT in an 18 month-old female child is presented.A left pulmonary mass was incidentally found on the computerized tomography (CT) scan of a child with persistent systemic inflammatory syndrome. Biopsy confirmed the diagnosis; after preoperative corticotherapy, left pneumonectomy was performed. The pericardium and left atrium were invaded and resected, requiring pericardial reconstruction. There is no relapse at four years of follow-up.Steroids play a role in tumor size reduction, but marginal resection is the gold standard. Extended approaches are feasible and often required in advanced cases. PMID- 26853246 TI - Chinese yellow wine. PMID- 26853247 TI - The clinical challenge of concomitant aortic and mitral valve stenosis. AB - The coexistence of mitral and aortic stenosis is not exceptional. Whereas rheumatic fever is currently plummeting in the Western countries, the incidence of degenerative disease is inversely increasing. The haemodynamic interactions which may interfere both with the usual echocardiographic parameters and with the invasive assessment may render the diagnosis difficult. The therapeutic challenges raised by this entity should not be underestimated. The increased morbidity and mortality of multivalvular surgery has to be balanced with the risk of a second operation down the line if one valvular involvement, deemed of a lesser importance, is neglected. This complex situation requires the multidisciplinary approach of a heart team involving surgeons, cardiologists, geriatrists if need be and imaging specialists. PMID- 26853248 TI - Summary 2015 ESC guidelines. PMID- 26853249 TI - Pre-hospital management of acute coronary syndrome patients in Belgium and Luxembourg and other Western European countries. AB - OBJECTIVES: This sub-analysis of the EPICOR study describes pre-hospital care (PHC) patterns in Belgium, Luxembourg (Belux) and Western European (WEU) countries (Finland, Norway, Denmark, the Netherlands, UK, Belgium, Luxembourg, Spain, France, Italy, Greece and Germany. METHODS AND RESULTS: EPICOR (NCT01171404) is multinational, observational study comprising patients with acute coronary syndrome hospitalized within 24h of symptoms onset, diagnosed with ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) or unstable angina (UA). Of the 325 WEU centres, 37 were in Belgium and 1 in Luxembourg. PHC was defined as pre-hospital ECG and/or pre-hospital medication (PHM). 504 Belux and 6,119 WEU patients were enrolled. Of the WEU patients 51.5% received PHC and 28.1% PHM, compared to 27.6% and 11.3% of the Belux patients. These differences were observed in both STEMI and UA/NSTEMI patients. In Belux, the most frequent PHM was acetylsalicylic acid (53 patients); only 1 patient received thrombolytics. The median time from symptoms onset to ECG was longer for Belux (2.8 h) than for WEU patients (2.4 h). PHC shortened this time by almost 1.5h. Belux patients with PHC had a shorter median time between symptoms onset and first medical attention (FMA) than WEU patients (1.0 vs 1.3 h). Only 34.7% of Belux patients with pre-hospital ECG and with time from FMA to ECG available had ECG within 10 minutes of FMA, as recommended by the European Society of Cardiology. CONCLUSIONS: In Belux, diagnostic ECG is delayed compared to WEU, despite the short time to FMA. Few patients undergo ECG within the recommended period, indicating room for improvement. PMID- 26853250 TI - Effects of Chinese yellow wine on nitric oxide synthase and intercellular adhesion molecule-1 expressions in rat vascular endothelial cells. AB - OBJECTIVE: The objective of this study was to determine similarities in the effect of yellow wine as compared to statin and the possibility that yellow wine inhibits tumour necrosis factor-alpha (TNF-alpha)-induced nitric oxide (NO) synthesis, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and intercellular adhesion molecule-1 (ICAM-1) in cultured rat vascular endothelial cells (VECs). METHODS: We isolated VECs, and cultivated and purified Sprague Dawley (SD) rat thoracic aortas in vitro. We selected the optimal wine concentration using clonogenic and MTT assays to measure cell survival. Next, we divided the cells into 9 groups: (1) control, (2) TNF-alpha, (3) TNF-alpha + rosuvastatin (10 MUmol/L), (4) TNF-alpha + ethanol 0.5%, (5) TNF alpha + yellow wine 0.5%, (6) TNF-alpha + ethanol 1.0%, (7) TNF-alpha + yellow wine 1.0%, (8) TNF-alpha + ethanol 1.5%, and (9) TNF-alpha + yellow wine 1.5% and they were given the corresponding treatment for 24 h. We determined NO production with nitrate reductase. We then measured eNOS activity, and detected eNOS, iNOS, and ICAM-1 protein levels by Western blotting. RESULTS: Compared with the TNF alpha group, NO production, eNOS activity, and eNOS protein expression in the rosuvastatin, and yellow wine 1.0%, and 1.5% groups were significantly increased. Protein expression of iNOS and ICAM-1 in the rosuvastatin, yellow wine 1.0%, and 1.5% groups were significantly decreased. Compared with the rosuvastatin group, eNOS, iNOS, and ICAM-1 protein expression in the yellow wine (0.5% -1.5%) groups were significantly different. CONCLUSION: Treatment with yellow wine increased NO production, eNOS activity, and eNOS protein expression, which decreases iNOS and ICAM-1 protein expression. We conclude that yellow wine may have similar beneficial effects as rosuvastatin on the cardiovascular system. These effects may be attributed to their anti-atherosclerotic actions. PMID- 26853251 TI - The COMmon control of hypErtenSion and Therapeutic Attitudes in Belgium and Luxemburg study (COME STAI). AB - STUDY AIM: The aim of this study was to assess hypertension management in general practice in Belgium and Luxembourg, shortly before the publication of the 2013 ESH/ESC Guidelines for arterial hypertension management. METHODS: A total of 516 general physicians evaluated 10,078 consecutive hypertensive patients. All used the same definitions to assess cardiovascular risk. RESULTS: Systolic (S) blood pressure (BP) was 139 +/- 19 mmHg, diastolic (D) BP 80 +/- 11 mmHg, patients were 64 +/- 13 years old and their body mass index (BMI) was 28 +/- 5 kg/m2 (mean +/- SD). Treatment remained unchanged in 71% of the patients with a SBP >= 140 mmHg. Those on >= 2 antihypertensive drugs were older, had higher BMI, slower HR, higher perceived cardiovascular risk, but lower BP (all P <= 0.001 vs no and monotherapy groups). Patients in whom treatment was intensified were at higher cardiovascular risk, as substantiated by an increased prevalence of males, a higher BP, a faster HR and a larger BMI (all P <= 0.0001). High cardiovascular risk patients underwent more frequent treatment simplifications with fixed combination therapies or the addition of another antihypertensive class (all P <= 0.0001 vs not at high cardiovascular risk). Among the 523 patients older than 80 years with SBP >= 140 mmHg, treatment intensification occurred in 32% when SBP >= 150 mmHg, and in 10% when SBP was between 140 and 149 mmHg (P <= 0.0001). CONCLUSION: The COME STAI study suggests that there is still room for improvement in hypertension control in Belgium and Luxembourg. PMID- 26853252 TI - Gender differences in dual-chamber pacemaker implantation indications and long term outcomes. AB - OBJECTIVE: Dual-chamber (DDD) pacing is the most commonly used mode of heart stimulation. The data on gender-related differences in the long-term follow-up of DDD pacing mode are still limited. We performed a retrospective single-centre study to determine the effect of gender on the implantation indications and the incidence of adverse events resulting in DDD mode loss. METHODS AND RESULTS: A group of 1,049 consecutive patients with DDD pacemaker implanted between 1984 and 2002 were followed up until 2014. The study group consisted of 995 patients who performed at least one follow-up visit. Follow-up period was 124.2 +/- 68.3 months, mean age was 63.5 +/- 12.4 years, 56% were male. Adverse events were defined as loss of primary DDD stimulation--lead malfunction, progression to permanent AF, and infective complications. Women were older than men (64.7 vs 62.6 years) at the time of implantation and they remained, on average, 1.5 year longer in follow-up compared with men. Female patients had significantly more SSS, history of paroxysmal AF, and a similar percentage of AVB compared with male patients. The incidence of lead malfunction, device-related infections, and progression to permanent AF did not show significant differences. However, in the group without prior paroxysmal AF, women developed permanent AF more frequently. CONCLUSIONS: This patients cohort showed that there is an association between gender and indications to DDD pacing therapy. The rate of adverse events was similar in both genders. Women had a significantly longer duration of follow-up, despite markedly higher age at implantation. PMID- 26853254 TI - Prevalence and correlates of mitral regurgitation in the current era: an echocardiography study of a Chinese patient population. AB - OBJECTIVE: Little is known about the prevalence of mitral regurgitation (MR) in China until now. The objective of the study was to survey the prevalence, correlates and causes of MR in a large Chinese patient population in the current era. METHODS: This study retrospectively analysed the echocardiographic database of the subjects visiting our heart centre from 2010 to 2012. RESULTS: A total of 134,874 cases were included into the analysis. Of these cases 42.44%, 1.63%, 1.44% had mild MR(+), moderate MR(2+) and severe MR(3+/4+), respectively. The rate of MR increased with age. The rate of severe MR was 22.14% in subjects with a left ventricular ejection fraction (LVEF) < 30%, 13.0% in subjects with a LVEF of 30-44%, 15.74% in subjects with left ventricular end-systolic diameter (LVSD) of 50-59 mm, and 27.28% in those with LVSD >= 60 mm. The aetiology of 1,948 cases of severe MR was as follows: 972 (49.9%) patients had primary causes, of whom 55 had rheumatic heart disease, 96 had infectious endocarditis, 141 had papillary muscle dysfunction and 608 had degenerative disease, and the other 976 patients had secondary MR. CONCLUSION: MR is common in subjects referring to our heart centre in China. Severe MR is frequent in patients with decreased LVEF or an enlarged left ventricle or atrium. Degenerative disease and secondary changes are the most common causes for severe MR. PMID- 26853253 TI - ST-segment elevation in lead aVR in the setting of acute coronary syndrome. AB - OBJECTIVES: The purpose of our study was to assess the value of aVR ST-segment elevation (STE) during acute non ST-segment elevation myocardial infarction (NSTEMI) or unstable angina. BACKGROUND: STE in lead aVR has been associated with severe coronary lesions in patients with acute coronary syndromes. However, there are conflicting data regarding the prognostic significance of this finding. METHODS: We evaluated the initial electrocardiogram (ECG) in 129 patients admitted to our hospital with acute NSTEMI or unstable angina without STE in leads other than aVR or V1. STE in aVR lead was measured and echocardiography and coronary angiography were performed within 48-72 hours after hospitalization. RESULTS: Overall, 40.3% (52 patients) had more than 0.05 mv STE in lead aVR. These patients had an increased prevalence of ST >= 1 mm in lead V1, a more frequent and extensive ST-segment depression (STD) in other leads, a higher prevalence of anterior and lateral STD and a lower frequency of isolated negative T waves. It was also strongly associated with cardiac enzyme rising and a trend toward higher 3-month mortality. Furthermore, patients with STE in lead aVR were more likely to have three-vessel or multivessel disease, higher Gensini score of the coronary arteries, lower left ventricular ejection fraction (LVEF) and higher incidence of mitral regurgitation (MR). CONCLUSIONS: Our study showed that among ECG markers, the sole criterion STE in lead aVR was independently associated with atherosclerosis severity and decreased LVEF. Also, it was significantly associated with the presence of MR. PMID- 26853255 TI - Higher cancer antigen 125 level is associated with the presence of permanent atrial fibrillation in systolic heart failure patients. AB - INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia in heart failure (HF). Recent studies have shown that serum cancer antigen-125 (CA-125) levels are elevated in HF, and high levels of CA-125 in HF patients with sinus rhythm have been shown to be associated with the development of new onset AF. However, the relation between CA-125 levels and the presence of AF in HF is unknown. In this study we investigated whether plasma CA-125 levels in patients with systolic HF could predict the presence of AF. METHODS: The study was a retrospective cohort design including 205 stable systolic HF patients who were selected during outpatient clinic visits and who had CA-125 measurement and an electrocardiogram within the last one month before admittance to cardiology clinic. Patients were classified into two groups based on the presence of AF (n = 67) or sinus rhythm (n = 138). RESULTS: The mean age of the patients was 68 +/- 11 years. CA-125 levels were significantly higher in patients with AF than patients with SR [33 (3 273) vs 102 (7-296) U/ml, P < 0.001]. CA-125 level, presence of right ventricular dilatation, pericardial effusion, moderate to severe TR and MR, and left atrial diameter were found to be associated with the presence of AF in univariate analysis. In a multivariate logistic regression model, only the CA-125 level remained associated. Also, according to the ROC curve analysis, the optimal cut off level of CA-125 for predicting AF was >= 91 U/mL with a specificity of 84% and a sensitivity of 54%. CONCLUSION: We have shown that the CA-125 levels can be used to predict AF in patients with systolic HF. PMID- 26853256 TI - Renal sympathetic denervation improves rate control in patients with symptomatic persistent atrial fibrillation and hypertension. AB - AIM: The aim of this study was to investigate whether renal sympathetic denervation (RSD) improves ventricular heart rate (HR) control in patients with persistent atrial fibrillation (AF). METHODS AND RESULTS: Twenty-one patients (aged 57.5 +/- 10.2 years, 76.2% male) with persistent AF and hypertension underwent RSD and completed 7-days follow-up evaluations, including 24-hour Holter monitoring (Holter), blood pressure (BP), 24-hour ambulatory BP monitoring (ABPM). Patients were grouped into tertiles of average HR at baseline Holter recording for evaluation of RSD effects on atrioventricular (AV) node (group 1: HR ? 90 bpm; group 2: 80 bpm ? HR < 90 bpm; group 3: HR < 80 bpm). RESULTS: All patients successfully underwent RSD without any complications. The clinical and procedural characteristics were similar in all groups of patients. No significant changes in BP were observed in the three groups before and after RSD. Compared with baseline, the average HR (Holter) of patients in group 1, 2 and 3 had a reduction of 22.6 +/- 13.2 bpm (83.3 +/- 4.9 vs 106.0 +/- 14.6, P = 0.004), 9.7 +/- 7.8 bpm (75.7 +/- 7.6 vs 85.4 +/- 3.7, P = 0.017) and 2.3 +/- 2.9 bpm (71.4 +/- 4.0 vs 73.7 +/- 4.7, P = 0.089) at 7 days after RSD, respectively. CONCLUSIONS: RSD could improve ventricular HR control in patients with persistent AF. RSD slowed AV node conduction in baseline HR-dependent manner. RSD may become an alternative non-pharmaceutical tool for rate control in patients with persistent AF. PMID- 26853258 TI - Belgian Society of Cardiology, 35th Annual Congress, 28th & 29th January, 2016 - SQUARE Brussels congress centre. PMID- 26853257 TI - Cardiac involvement in hypereosinophilic syndrome. PMID- 26853259 TI - Corrigendum. PMID- 26853261 TI - Joint estimation over multiple individuals improves behavioural state inference from animal movement data. AB - State-space models provide a powerful way to scale up inference of movement behaviours from individuals to populations when the inference is made across multiple individuals. Here, I show how a joint estimation approach that assumes individuals share identical movement parameters can lead to improved inference of behavioural states associated with different movement processes. I use simulated movement paths with known behavioural states to compare estimation error between nonhierarchical and joint estimation formulations of an otherwise identical state space model. Behavioural state estimation error was strongly affected by the degree of similarity between movement patterns characterising the behavioural states, with less error when movements were strongly dissimilar between states. The joint estimation model improved behavioural state estimation relative to the nonhierarchical model for simulated data with heavy-tailed Argos location errors. When applied to Argos telemetry datasets from 10 Weddell seals, the nonhierarchical model estimated highly uncertain behavioural state switching probabilities for most individuals whereas the joint estimation model yielded substantially less uncertainty. The joint estimation model better resolved the behavioural state sequences across all seals. Hierarchical or joint estimation models should be the preferred choice for estimating behavioural states from animal movement data, especially when location data are error-prone. PMID- 26853260 TI - A Novel PET Imaging Probe for the Detection and Monitoring of Translocator Protein 18 kDa Expression in Pathological Disorders. AB - A new fluorine-substituted ligand, compound 1 (CB251), with a very high affinity (Ki = 0.27 +/- 0.09 nM) and selectivity for the 18-kDa translocator protein (TSPO), is presented as an attractive biomarker for the diagnosis of neuroinflammation, neurodegeneration and tumour progression. To test compound 1 as a TSPO PET imaging agent in vivo, 2-(2-(4-(2-[(18)F]fluoroethoxy)phenyl)-6,8 dichloroimidazo[1,2-a]pyridin-3-yl)-N,N-dipropylacetamide ([(18)F]1; [(18)F]CB251) was synthesized by nucleophilic aliphatic substitution in a single step radiolabelling procedure with a 11.1 +/- 3.5% (n = 14, decay corrected) radiochemical yield and over 99% radiochemical purity. In animal PET imaging studies, [(18)F]CB251 provided a clearly visible image of the inflammatory lesion with the binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND 1.83 +/- 0.18), in a neuroinflammation rat model based on the unilateral stereotaxic injection of lipopolysaccharide (LPS), comparable to that of [(11)C]PBR28 (BPND 1.55 +/- 0.41). [(18)F]CB251 showed moderate tumour uptake (1.96 +/- 0.11%ID/g at 1 h post injection) in human glioblastoma U87-MG xenografts. These results suggest that [(18)F]CB251 is a promising TSPO PET imaging agent for neuroinflammation and TSPO rich cancers. PMID- 26853262 TI - Posture analysis among Flemish secondary school teachers: difference between the use of chalkboards and electronic school boards during classroom teaching. AB - The aim of this study was to (i) make a posture analysis of teachers during theoretical classroom teaching; (ii) to estimate the risk for the development of musculoskeletal problems (MSP); (iii) test the hypotheses that an electronic school board (EB) has more ergonomic advantages for teachers. Thirty-five secondary school teachers, of which 15 used an EB and 20 used chalkboards, were selected by convenience sampling and filmed during 30 min of a theoretical course. Posture analysis of back, arms, legs and risk assessment was performed using the Ovako Working Posture Analysis System. Most of the teachers' postures did not indicate a higher risk for MSP. However, some postures may be harmful when accumulated for several hours of teaching a day; especially, long periods of standing and standing with a bended back. Results also indicated that currently the use of an EB does not improve teachers' posture. Practitioner Summary: The relationship between objectively measured physical work load and risk for injuries among teachers was not analysed so far. In this study teachers' posture was analysed using the OWAS method. Prolonged standing and forward bending were identified as risk postures. Also, using an electronic school board currently does not improve posture. PMID- 26853263 TI - Improving prevention: risk scores, imaging, and PCSK9 inhibitors. PMID- 26853264 TI - CardioPulse: The European Medicines Agency's approval of proprotein convertase subtilisin/kexin type 9 inhibitors.. PMID- 26853266 TI - Differentially pumped spray deposition as a rapid screening tool for organic and perovskite solar cells. AB - We report a spray deposition technique as a screening tool for solution processed solar cells. A dual-feed spray nozzle is introduced to deposit donor and acceptor materials separately and to form blended films on substrates in situ. Using a differential pump system with a motorised spray nozzle, the effect of film thickness, solution flow rates and the blend ratio of donor and acceptor materials on device performance can be found in a single experiment. Using this method, polymer solar cells based on poly(3-hexylthiophene) (P3HT):(6,6)-phenyl C61 butyric acid methyl ester (PC61BM) are fabricated with numerous combinations of thicknesses and blend ratios. Results obtained from this technique show that the optimum ratio of materials is consistent with previously reported values confirming this technique is a very useful and effective screening method. This high throughput screening method is also used in a single-feed configuration. In the single-feed mode, methylammonium iodide solution is deposited on lead iodide films to create a photoactive layer of perovskite solar cells. Devices featuring a perovskite layer fabricated by this spray process demonstrated a power conversion efficiencies of up to 7.9%. PMID- 26853265 TI - The exploration of network motifs as potential drug targets from post translational regulatory networks. AB - Phosphorylation and proteolysis are among the most common post-translational modifications (PTMs), and play critical roles in various biological processes. More recent discoveries imply that the crosstalks between these two PTMs are involved in many diseases. In this work, we construct a post-translational regulatory network (PTRN) consists of phosphorylation and proteolysis processes, which enables us to investigate the regulatory interplays between these two PTMs. With the PTRN, we identify some functional network motifs that are significantly enriched with drug targets, some of which are further found to contain multiple proteins targeted by combinatorial drugs. These findings imply that the network motifs may be used to predict targets when designing new drugs. Inspired by this, we propose a novel computational approach called NetTar for predicting drug targets using the identified network motifs. Benchmarking results on real data indicate that our approach can be used for accurate prediction of novel proteins targeted by known drugs. PMID- 26853267 TI - Agriculture causes nitrate fertilization of remote alpine lakes. AB - Humans have altered Earth's nitrogen cycle so dramatically that reactive nitrogen (Nr) has doubled. This has increased Nr in aquatic ecosystems, which can lead to reduced water quality and ecosystem health. Apportioning sources of Nr to specific ecosystems, however, continues to be challenging, despite this knowledge being critical for mitigation and protection of water resources. Here we use Delta(17)O, delta(18)O and delta(15)N from Uinta Mountain (Utah, USA) snow, inflow and lake nitrate in combination with a Bayesian-based stable isotope mixing model, to show that at least 70% of nitrates in aquatic systems are anthropogenic and arrive via the atmosphere. Moreover, agricultural activities, specifically nitrate- and ammonium-based fertilizer use, are contributing most (~60%) Nr, and data from other North American alpine lakes suggest this is a widespread phenomenon. Our findings offer a pathway towards more effective mitigation, but point to challenges in balancing food production with protection of important water resources. PMID- 26853268 TI - Hyperglycemia and its association with clinical outcomes in postsurgical neonates and small infants in the intensive care unit. AB - PURPOSE: The aim of the research was to investigate the association between postsurgical hyperglycemia of neonates and small infants (<6months) during their stays in intensive care unit and clinical outcomes. METHODS: A retrospective study of 180 patients including neonates and small infants (<6months) admitted to pediatric intensive care unit (PICU) after major abdominal and thoracic surgeries from July 2012 to December 2014 was performed. Clinical data including serum glucose levels, surgical procedures, PICU length of stays, total length of hospital stays, systemic infections and wound infections were recorded and analyzed. Surgical diagnosis and Pediatric Risk of Mortality III (PRISM III) score were analyzed as confounding factors. RESULTS: Maximum glucose values (Gmax) ranged from 4.8 to 32.9mmol/L (median level: 8.4mmol/L). Hyperglycemia was prevalent among this group of patients. 93.3% of them experienced hyperglycemia (>6.1mmol/L) and 20% had severe hyperglycemia (>11.0mmol/L). Both PICU length of stays and total hospital length of stays increased as Gmax increased (P<0.001). This trend was still statistically significant when either surgical diagnosis or PRISM score had been controlled as confounding factors. Death rates and infectious rates were not significantly different among four groups of patients with different Gmax. CONCLUSIONS: Hyperglycemia was prevalent in postsurgical neonates and small infants in PICU and was associated with increased PICU and hospital stays. PMID- 26853269 TI - Headspace Microextraction of Sulfonamides from Honey by Hollow Fibers Coupled with Ultrasonic Nebulization. AB - A new method for the rapid simultaneous determination of five sulfonamides in honey was developed using ultrasonic nebulization-assisted extraction coupled with hollow fiber liquid-liquid-liquid microextraction prior to liquid chromatography. In the present method, the sample solution was nebulized by ultrasonication. Sulfonamides in the aerosol particles were extracted by 1 octanol impregnated in the pores of a hollow fiber and further into the acceptor phase (acid solution, pH 2.0) contained in the lumen of the hollow fiber. Several experimental parameters that affect the extraction efficiency were optimized. The present method provides good recoveries (88.9-114.2%) and acceptable precision (<10.7%), indicating the effective extraction. The detection limits were 4.6-6.8 MUg/kg, lower than the maximum residue limits of sulfonamides in honeys. Compared to the traditional extraction methods, the present method requires less organic solvent and operation time, demonstrating excellent cleanup ability and good enrichment efficiency. PMID- 26853270 TI - Proteinuria: New therapeutic strategy for proteinuria. PMID- 26853272 TI - Mineral and bone disorders: Targeting CYP24A1. PMID- 26853277 TI - Genetics: GWAS identifies 24 new loci for renal function. PMID- 26853279 TI - Diethyl Phosphite Initiated Coupling of alpha-Ketoesters with Imines for Synthesis of alpha-Phosphonyloxy-beta-amino Acid Derivatives and Aziridine-2 carboxylates. AB - Coupling of alpha-ketoesters with imines initiated by diethyl phosphite in the presence of alkaline metal hexamethyldisilazides is reported. Base-promoted addition of diethyl phosphite to alpha-ketoesters, followed by [1,2] phosphonate/phosphate rearrangement, generates alpha-phosphonyloxy enolates that are subsequently intercepted by imines. The use of suitable azomethine coupling partners allows selective construction of syn-alpha-hydroxy-beta-amino acid derivatives or trans-aziridine-2-carboxylates in high yields with excellent diastereoselectivities. PMID- 26853278 TI - [Dualistic classification of epithelial ovarian cancer: Is it clinically relevant?]. AB - Malignant epithelial tumors (carcinomas) are the most common ovarian cancers and the most lethal gynecological malignancies. Based on their heterogeneous morphology, a dualistic model of carcinogenesis was proposed in 2004. Type I carcinomas, composed of low grade serous, endometrioid, mucinous, clear cell carcinomas and malignant Brenner tumors, were distinct from type II carcinomas (high grade serous, undifferentiated carcinomas and carcinosarcomas). However, clinical studies failed to demonstrate the prognostic value of such a classification. The main reproach to this dualistic model was that it lumped together in type I tumors, heterogeneous lesions such as clear cell and mucinous carcinomas. Recent advances on molecular genetic alterations and precursor lesions favor the classification of ovarian carcinomas as five distinct diseases. The dualistic model of carcinogenesis in type I and II can finally be applied only to serous ovarian carcinomas (low grade and high grade). PMID- 26853275 TI - Mesenchymal stromal cells in renal transplantation: opportunities and challenges. AB - Lifelong immunosuppressive therapy is essential to prevent allograft rejection in transplant recipients. Long-term, nonspecific immunosuppression can, however, result in life-threatening complications and fail to prevent chronic graft rejection. Bone marrow (BM)-derived multipotent mesenchymal stromal cells (MSCs) have emerged as a potential candidate for cell-based therapy to modulate the immune response in organ transplantation. These cells can repair tissue after injury and downregulate many of the effector functions of immune cells that participate in the alloimmune response, converting them into regulatory cells. The findings of preclinical and initial clinical studies support the potential tolerance-inducing effects of MSCs and highlight the unanticipated complexity of MSC therapy in kidney transplantation. In animal models of transplantation MSCs promote donor-specific tolerance through the generation of regulatory T cells and antigen-presenting cells. In some settings, however, MSCs can acquire proinflammatory properties and contribute to allograft dysfunction. The available data from small clinical studies suggest that cell infusion is safe and well tolerated by kidney transplant recipients. Ongoing and future trials will provide evidence regarding the long-term safety of MSC therapy and determine the optimum cell source (either autologous or allogeneic) and infusion protocol to achieve operational tolerance in kidney transplant recipients. These studies will also provide additional evidence regarding the risks and benefits of MSC infusion and will hopefully offer definitive answers to the important questions of when, where, how many and which types of MSCs should be infused to fully exploit their immunomodulatory, pro-tolerogenic and tissue-repairing properties. PMID- 26853280 TI - Hyperinflammation in patients with chronic granulomatous disease leads to impairment of hematopoietic stem cell functions. AB - BACKGROUND: Defects in phagocytic nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) function cause chronic granulomatous disease (CGD), a primary immunodeficiency characterized by dysfunctional microbicidal activity and chronic inflammation. OBJECTIVE: We sought to study the effect of chronic inflammation on the hematopoietic compartment in patients and mice with X-linked chronic granulomatous disease (X-CGD). METHODS: We used immunostaining and functional analyses to study the hematopoietic compartment in patients with CGD. RESULTS: An analysis of bone marrow cells from patients and mice with X-CGD revealed a dysregulated hematopoiesis characterized by increased numbers of hematopoietic progenitor cells (HPCs) at the expense of repopulating hematopoietic stem cells (HSCs). In patients with X-CGD, there was a clear reduction in the proportion of HSCs in bone marrow and peripheral blood, and they were also more rapidly exhausted after in vitro culture. In mice with X-CGD, increased cycling of HSCs, expansion of HPCs, and impaired long-term engraftment capacity were found to be associated with high concentrations of proinflammatory cytokines, including IL 1beta. Treatment of wild-type mice with IL-1beta induced enhanced cell-cycle entry of HSCs, expansion of HPCs, and defects in long-term engraftment, mimicking the effects observed in mice with X-CGD. Inhibition of cytokine signaling in mice with X-CGD reduced HPC numbers but had only minor effects on the repopulating ability of HSCs. CONCLUSIONS: Persistent chronic inflammation in patients with CGD is associated with hematopoietic proliferative stress, leading to a decrease in the functional activity of HSCs. Our observations have clinical implications for the development of successful autologous cell therapy approaches. PMID- 26853281 TI - Omacetaxine Mepesuccinate for Chronic Myeloid Leukemia. AB - Omacetaxine mepesuccinate is approved by the Food and Drug Administration in the United States for the treatment of chronic myeloid leukemia in chronic or accelerated phase resistant to two or more tyrosine kinase inhibitors. This review summarizes the mode of action, pharmacokinetics, efficacy and safety of omacetaxine mepesuccinate. Omacetaxine mepesuccinate has activity in chronic myeloid leukemia, especially in the chronic phase, regardless of the presence of ABL1 kinase domain mutations. Omacetaxine mepesuccinate has distinct but manageable adverse events profile. Omacetaxine mepesuccinate is a treatment option for a subset of patients with refractory chronic myeloid leukemia. PMID- 26853283 TI - Universal Scientific Education and Research Network (USERN):a New Horizon for Science. PMID- 26853282 TI - Spatio-temporal regulations and functions of neuronal alternative RNA splicing in developing and adult brains. AB - Alternative pre-mRNA splicing is a fundamental mechanism that generates molecular diversity from a single gene. In the central nervous system (CNS), key neural developmental steps are thought to be controlled by alternative splicing decisions, including the molecular diversity underlying synaptic wiring, plasticity, and remodeling. Significant progress has been made in understanding the molecular mechanisms and functions of alternative pre-mRNA splicing in neurons through studies in invertebrate systems; however, recent studies have begun to uncover the potential role of neuronal alternative splicing in the mammalian CNS. This article provides an overview of recent findings regarding the regulation and function of neuronal alternative splicing. In particular, we focus on the spatio-temporal regulation of neurexin, a synaptic adhesion molecule, by neuronal cell type-specific factors and neuronal activity, which are thought to be especially important for characterizing neural development and function within the mammalian CNS. Notably, there is increasing evidence that implicates the dysregulation of neuronal splicing events in several neurological disorders. Therefore, understanding the detailed mechanisms of neuronal alternative splicing in the mammalian CNS may provide plausible treatment strategies for these diseases. PMID- 26853284 TI - Challenges of Epidemiologists of Developing Countries in the 21st Century. AB - There are many published articles which cover current and future challenges of epidemiology. However, up until now, most of them are written by developed world epidemiologists. Therefore, despite a common use of assumptions, they did not have the opportunity to discuss the different range of practical tasks and priorities away from developed countries. The topics covered are; facing poverty, non-democratic government that has links to developed countries, man-made and natural disasters, handling low-quality data and accessing it, and finally improving contribution to the world epidemiological knowledge for the 21st century. PMID- 26853285 TI - Evaluation of Cytogenetic Alterations in Peripheral Blood Lymphocytes of Esophageal Cancer Patients Treated with Radiotherapy or Chemoradiotherapy using Cytokinesis-Blocked Micronucleus Assay. AB - The effects of combined radiotherapy (RT) and chemotherapy in the severity of cytogenetic alterations expressed as micronucleus (MN) in peripheral blood lymphocytes of patients treated for esophageal cancer was evaluated. To do this, blood was obtained from 23 and 15 esophageal cancer patients scheduled for chemo radiotherapy and RT alone, respectively, before, during, and after treatment. Blood samples were cultured in RPMI-1640 complete medium containing 1% phytohemagglutinin and incubated in a CO2 incubator. Cytochalasin-B was added to the cultures at a final concentration of 5 MUg/ml. Finally, harvesting, slide making, and analysis were performed according to standard procedures. Results indicate that there was no significant difference between the frequencies of MN in lymphocytes of individuals before being treated with RT alone or chemo radiotherapy. In the middle of treatment, (after 12 fractions of RT) the frequency of MN increased significantly compared with their concurrent pre treatment samples in both groups (four-fold). However, the frequency of MN observed for RT patients was not significantly different with those received chemo- and radiotherapy. At the end of treatment, (after 24 fractions of radiotherapy) an increase in the MN frequency was observed for chemo-radiation group significantly higher than RT group (P=0.022). Mild increase in MN frequency in lymphocytes of patients receiving chemoradiation only after the completion of treatment course might be indicative of resistance induced by chemotherapeutics to the clastogenic effects of radiation. Therefore, using these agents repeatedly for cancer treatment in combination with radiation might not cause severe adverse biological effects in normal tissues. PMID- 26853286 TI - The Therapeutic Role of Vasopressin on Improving Lactate Clearance During and After Vasogenic Shock: Microcirculation, Is It The Black Box? AB - Arginine vasopressin as a supplementary vasopressor in septic shock restores vascular tone and mean arterial pressure, meanwhile decreases dose and exposure time to catecholamines. The objective of this study was to evaluate the effect of vasopressin on lactate and lactate clearance as markers of tissue perfusion during septic shock. In this prospective, randomized, controlled trial, 30 patients with septic shock were enrolled in two groups. One group received norepinephrine infusion (titrated to reach the target MAP of >=65 mm Hg) and the other group in addition to norepinephrine, received vasopressin at a constant rate of 0.03 u/min. Serum lactate levels were assessed at baseline, 24 and 48 hours after randomization. Lactate clearance was estimated for each patient at 24 and 48 hours. Venous lactate was measured in both groups. Despite a tendency toward higher venous lactate at 24 and 48 hours in the norepinephrine group (3.1 vs. 2.5, P=0.67 and 1.7 vs. 1.1, P=0.47), the conflict was not statistically significant among them. While lactate clearance after 24 hours was significantly higher in vasopressin treatment group (46% vs. 20%, respectively; P=0.048), the 48-hour lactate clearance did not differ from statistic viewpoints despite their clinical values (66% vs. 40%, P=0.17). Although lactate levels did not significantly differ between treatment groups, lactate clearance at 24 hours was significantly higher in vasopressin group. This may be the effect of vasopressin effect on microcirculation and tissue hypoperfusion or its catecholamine sparing effect. PMID- 26853287 TI - The Preventive Effect of L-Lysine on Lysozyme Glycation in Type 2 Diabetes. AB - Lysozyme is a bactericidal enzyme whose structure and functions change in diabetes. Chemical chaperones are small molecules including polyamines (e.g. spermine), amino acids (e.g. L-lysine) and polyols (e.g. glycerol). They can improve protein conformation in several stressful conditions such as glycation. In this study, the authors aimed to observe the effect of L-lysine as a chemical chaperone on structure and function of glycated lysozyme. In this study, in vitro and in vivo effects of L-lysine on lysozyme glycation were investigated. Lysozyme was incubated with glucose and/or L-lysine, followed by an investigation of its structure by electrophoresis, fluorescence spectroscopy, and circular dichroism spectroscopy and also assessment of its bactericidal activity against M. lysodeikticus. In the clinical trial, patients with type 2 diabetes mellitus (T2DM) were randomly divided into two groups of 25 (test and control). All patients received metformin and glibenclamide for a three months period. The test group was supplemented with 3 g/day of L-lysine. The quantity and activity of lysozyme and other parameters were then measured. Among the test group, L-lysine was found to reduce the advanced glycation end products (AGEs) in the sera of patients with T2DM and in vitro condition. This chemical chaperone reversed the alteration in lysozyme structure and function due to glycation and resulted in increased lysozyme activity. Structure and function of glycated lysozyme are significantly improved by l-lysine; therefore it can be considered an effective therapeutic supplementation in T2DM, decreasing the risk of infection in these patients. PMID- 26853288 TI - Effects of Ghrelin on Testicular Ischemia/Reperfusion-Induced Injury. AB - Ischemia-reperfusion injury is a possible cause of testicular damage and infertility after testicular torsion and detorsion. The purpose of this study was to evaluate the effect of ghrelin on testicular ischemia-reperfusion damage. A total of 30 adult male rats were selected for the study and divided randomly into 3 groups, each containing 10 rats. Animals in the testicular torsion and ghrelin treated groups were subjected to unilateral 720 degrees counterclockwise testicular torsion for 1 hour, and then reperfusion was allowed after detorsion for 7 and 30 days. The ghrelin-treated group and the other two groups received intraperitoneally 40 nmol of ghrelin and physiological saline 15 min before detorsion, respectively. The animals were sacrificed at the end of reperfusion times, and their testes were taken for later histopathological examination. The seminiferous tubules diameter, germinal epithelium height, as well as volume densities in testicular torsion / detorsion plus saline group, were significantly lesser versus control group, which clearly indicates an ischemia-reperfusion injury. Ghrelin treatment resulted in a partial increment in examined histological parameters on day 30 after reperfusion. Current results showed that ghrelin ameliorates the testicular ischemia-reperfusion damage. PMID- 26853289 TI - Isolation and Identification Enterobacter asburiae from Consumed Powdered Infant Formula Milk (PIF) in the Neonatal Intensive Care Unit (NICU). AB - Enterobacter asburiae (E. asburiae) is a facultative anaerobic, non-spore-forming gram-negative rod-shaped bacterium belonging to the family of Enterobacteriaceae. It is an opportunistic pathogen that its strains are isolated from a variety of clinical and environmental specimens. Since powdered infant formula milk (PIF) is not a sterile product, it is an excellent medium for bacterial growth. The aim of this study was to isolate and identify E. asburiae from PIF in the neonatal intensive care unit (NICU) and determine antimicrobial susceptibility patterns of this bacterium. A total 125 PIF samples were purchased from drug stores between June 2011 to March 2012. E. asburiae was isolated according to FDA method. For final confirmation, biochemical tests embedded in the API-20E system were used. The drug susceptibility test was performed using the disc diffusion method according to CLSI recommendations. Out of the 125 PIF samples investigated, 2 (1.6%) samples were positive for E. asburiae. All isolated strains were uniformly susceptible to aztreonam, cefotaxim, amikacin, streptomycin, nalidixic acid, meropenem, tetracycline, ceftazidime, and colistin. Variable susceptibility was seen to the some antimicrobial agents tested. Each country should categorize its own designed guidelines for the preparation and handling of PIF adapted to the local environment. Moreover, the pathogenesis of the E. asburiae in infants hospitalized in NICU and other groups such as immunosuppressed patients and HIV infected individuals is uncertain and requires further study. PMID- 26853290 TI - Plasmodium falciparum Merozoite Surface Protein-1 Polymorphisms among Asymptomatic Sickle Cell Anemia Patients in Nigeria. AB - Asymptomatic malaria (ASM) has been implicated in the development of hemolytic crisis in infected sickle cell anemia (SCA) patients worldwide. This study surveyed steady state SCA Nigerian patients for ASM to investigate the influence of malaria prevention behaviors and age on parasitaemia and multiplicity of infection (MOI). A total of 78 steady SCA patients aged 5 - 27 years on routine care at three health facilities in Lagos were investigated for ASM by light microscopy and PCR with a multiplicity of infection determined by genotyping block 2 of merozoite surface protein 1 (msp1) gene of Plasmodium falciparum (P. falciparum). Use of malaria prevention measures was captured using a semi structured questionnaire. The prevalence rates of ASM (due to Pf only) by microscopy and PCR were found to be 27.3% and 47.4% respectively (P < 0.05) with a Mean + SEM parasite density of 2238.4 + 464.3 parasites/uL. Five distinct msp1 genotypes [K1 (2), MAD20 (2), RO33 (1)] were detected and significant (P<0.05) disparity in allele frequencies (K1, 91.8%, MAD20, 32.4%; RO33, 18.9%) was found. The overall MOI was 1.43 and 37.8% of infections were polyclonal (P<0.05). ASM was associated with non-use of preventive measures and occurred in 62.1% of SCA patients aged < 10y with lower MOI of 1.3 compared to 38.1% in older patients with a higher MOI of 1.5 (P<0.05). We conclude that PCR improved the diagnosis of ASM among Nigerian SCA patients with infections being of low complexity and associated with non-use of preventive interventions and R033 msp1 allele selection. PMID- 26853291 TI - Prevalence of Hepatitis B and C among Patients Looking for Hospital Care; Five Years' Study in Mashhad, Iran. AB - This study was conducted to find out the prevalence, viral load and co-infection of HBV and HCV infection among patients seeking to hospital care in Mashhad, Iran. A total of 402 samples (349 samples for HBV and 53 for HCV) were received and were screened for hepatitis B and C during 2004 to 2014. Viral loads of HBV DNA and HCV RNA were quantified by real-time PCR. Among 349 collected samples, 229 (65.61%) were positive for HBV DNA and 36 (67.92%) for HCV RNA. Among the ones positive for HBV DNA and HCV RNA, HCV was more prevalent (86.11% Vs 58%) ,in male patients, a higher incidence was attributed to HBV than HCV (34.42 Vs 13.88%%). The incidence of co-infection of HBV and HCV was in 5 (1.88%) patients. Association of age and load of HBV, HCV showed that higher marginal viral loads found to be more common in the age groups of upper 30 years old (P=0.064, P=0.079, respectively). The present study provides the preliminary information about high HCV and HBV prevalence. Findings from the current study will be helpful for the better management and control of viral hepatitis among patients looking for hospital care. PMID- 26853292 TI - Evaluating Knowledge, Attitude and Practice of Health-Care Workers Regarding Patient Education in Iran. AB - The objective of the study was to evaluate the position of patient education measuring knowledge, attitude, and practice (KAP) among health care workers (HCWs). It is also aimed to emphasize the need for a real position for patient education. This survey was performed among a group of HCWs in Iran. The scores had an acceptable level. However, nurses, females and younger people received higher scores. The staff was already aware of patient education necessity and considered it as the duty of all medical team. Often HCWs cannot include patient education in their routine due to time shortage, lack of staff's financial motivation, fatigue, and loads of work, etc. There is still need for a real training in the educational curriculum. Additionally, the various HCWs-related obstacles should be taken into account. PMID- 26853293 TI - Comparison between Intralesional Triamcinolone and Kligman's Formula in Treatment of Melasma. AB - Melasma is a common acquired skin disorder. While different treatments are currently being used, in many cases it is refractory to treatment. According to the effects of topical steroids in decreasing skin pigmentation, we studied the efficacy of this new method for treatment of melasma. A total of 42 women with facial melasma, admitted to the department of dermatology of Hamadan, were enrolled in the study. They were divided randomly into two groups (A and B), group A (case) received subepidermal triamcinolone injections with a dose of 4 mg per cc and 5 mm intervals until complete blanching of melasma lesions, and group B (control) received Kligman's formula (hydroquinone 5%, tretinoin 0.1%, and dexamethasone 0.1%). At the first visit, we completed the MASI score papers, and we repeated that at weeks 4 and 8 of the study. We followed them for two months, every two weeks. At each visit, side effects and clinical response to treatment were noted. A decrease in MASI was observed in both group (11.57 +/- 4.33 vs 9.31 +/- 3.75 at 4th week and vs 8.01 +/- 3.1 at 8th week, P-value < 0.001 in group A, and 10.46 +/- 5.61 vs 9.76 +/- 5.21 at 4th week and vs 8.96 +/- 4.96 at 8th week, P-value< 0.001 in group B). In comparison between 2 groups, response to treatment was much better in group A than group B (P-value<0.001). In comparison to topical treatments, based on these findings, triamcinolone microinjection is a new, safe and strong therapeutic method for treatment of melasma. PMID- 26853294 TI - A Rare Case of Splenic Torsion with Sigmoid Volvulus in a 14-Year-Old Girl. AB - Wandering spleen is an uncommon entity in adults and has been described only rarely with sigmoid volvulus, that rarely affects children and adolescents. It is usually described in adults.Wandering spleen characterized by the abnormal location of the spleen, caused by incomplete fusion of the four primary splenic ligaments, allowing the spleen to be mobile within the abdomen.The wandering spleen can lead to torsion and subsequent splenic infarction or rupture. Clinical suspicion plus urgent investigation and intervention are important. We present a rare clinical case of acute abdomen due to torsion of wandering spleen and volvulus of sigmoid in a 14-year-old girl presented with painful periumbilical mass. Detorsion of sigmoid occurred while undergoing exploratory laparotomy and splenectomy was performed. The possibility of torsion and its complication like gastric, pancreas tail and colon volvulus should be kept in mind in the differential diagnosis of the acute abdomen to avoid serious complications. PMID- 26853295 TI - Guillain-Barre Syndrome after Coronary Artery Bypass Graft Surgery: a Case Report. AB - Guillain-Barre syndrome is a neurologic disorder that may appear after infection or major surgery. Guillain-Barre syndrome following cardiac surgery is rare and only based on case reports, and we review all of the published cases. A 52-year old man after 5 months suffering from chest pain was referred to our hospital and underwent coronary artery bypass graft for 3 vessel disease. The patient was discharged without complication on the 5th postoperative day. He presented Guillain-Barre syndrome after 12 months. He has not completely recovered weakness of upper extremities grade 4/5 with atrophy of both upper extremities remains after 18 months. This disorder is similar to classic GBS. It is important to be alert to de novo autoimmune neurological disorders after cardiac surgery. These disorders are similar to classic autoimmune disease and treated with standard therapies. PMID- 26853296 TI - Huge Intracanal Lumbar Disc Herniation: a Review of Four Cases. AB - Lumbar disc herniation (LDH) is the most common cause of sciatica and only in about 10% of the affected patients, surgical intervention is necessary. The side of the patient (the side of most prominent clinical complaints) is usually consistent with the side of imaging (the side with most prominent disc herniation on imaging scans). In this case series, we presented our experience in four cases with huge intracanal LDH that a mismatch between the patient's side and the imaging's side was present. In these cases, for deciding to do the operation, the physicians need to rely more on clinical findings, but for deciding the side of discectomy, imaging characteristic (imaging side) may be a more important criterion. PMID- 26853297 TI - Colonic tuberculosis. PMID- 26853298 TI - Metastatic colon neuroendocrine carcinoma found in a patient with ulcerative colitis during annual endoscopic surveillance. PMID- 26853299 TI - A case of needle tract seeding after EUS-guided FNA in pancreatic cancer, detected by serial positron emission tomography/CT. PMID- 26853300 TI - Is there an optimal vitamin D status for immunity in athletes and military personnel? AB - Vitamin D is mainly obtained through sunlight ultraviolet-B (UVB) exposure of the skin, with a small amount typically coming from the diet.It is now clear that vitamin D has important roles beyond its well-known effects on calcium and bone homeostasis. Immune cells express the vitamin D receptor, including antigen presenting cells, T cells and B cells, and these cells are all capable of synthesizing the biologically active vitamin D metabolite, 1, 25 hydroxy vitamin D.There has been growing interest in the benefits of supplementing vitamin D as studies report vitamin D insufficiency (circulating 25(OH)D < 50 nmol/L) in more than half of all athletes and military personnel tested during the winter, when skin sunlight UVB is negligible. The overwhelming evidence supports avoiding vitamin D deficiency (25(OH)D< 30 nmol/L)to maintain immunity and prevent upper respiratory illness (URI) in athletes and military personnel.Recent evidence supports an optimal circulating 25(OH)D of 75 nmol/L to prevent URI and enhance innate immunity and mucosal immunity and bring about anti-inflammatory actions through the induction of regulatory T cells and the inhibition of pro inflammatory cytokine production. We provide practical recommendations for how vitamin D sufficiency can be achieved in most individuals by safe sunlight exposure in the summer and daily 1, 000 IU vitamin D3 supplementation in the winter. Studies are required in athletes and military personnel to determine the impact of these recommendations on immunity and URI; and,to demonstrate the purported benefit of achieving 25(OH)D>75 nmol/L. PMID- 26853301 TI - Direct Ventral Hippocampal-Prefrontal Input Is Required for Anxiety-Related Neural Activity and Behavior. AB - The ventral hippocampus (vHPC), medial prefrontal cortex (mPFC), and basolateral amygdala (BLA) are each required for the expression of anxiety-like behavior. Yet the role of each individual element of the circuit is unclear. The projection from the vHPC to the mPFC has been implicated in anxiety-related neural synchrony and spatial representations of aversion. The role of this projection was examined using multi-site neural recordings combined with optogenetic terminal inhibition. Inhibition of vHPC input to the mPFC disrupted anxiety and mPFC representations of aversion, and reduced theta synchrony in a pathway-, frequency- and task specific manner. Moreover, bilateral, but not unilateral, inhibition altered physiological correlates of anxiety in the BLA, mimicking a safety-like state. These results reveal a specific role for the vHPC-mPFC projection in anxiety related behavior and the spatial representation of aversive information within the mPFC. PMID- 26853302 TI - Inhibitory Synapses Are Repeatedly Assembled and Removed at Persistent Sites In Vivo. AB - Older concepts of a hard-wired adult brain have been overturned in recent years by in vivo imaging studies revealing synaptic remodeling, now thought to mediate rearrangements in microcircuit connectivity. Using three-color labeling and spectrally resolved two-photon microscopy, we monitor in parallel the daily structural dynamics (assembly or removal) of excitatory and inhibitory postsynaptic sites on the same neurons in mouse visual cortex in vivo. We find that dynamic inhibitory synapses often disappear and reappear again in the same location. The starkest contrast between excitatory and inhibitory synapse dynamics is on dually innervated spines, where inhibitory synapses frequently recur while excitatory synapses are stable. Monocular deprivation, a model of sensory input-dependent plasticity, shortens inhibitory synapse lifetimes and lengthens intervals to recurrence, resulting in a new dynamic state with reduced inhibitory synaptic presence. Reversible structural dynamics indicate a fundamentally new role for inhibitory synaptic remodeling--flexible, input specific modulation of stable excitatory connections. PMID- 26853304 TI - Mechanisms Underlying the Neuromodulation of Spinal Circuits for Correcting Gait and Balance Deficits after Spinal Cord Injury. AB - Epidural electrical stimulation of lumbar segments facilitates standing and walking in animal models and humans with spinal cord injury. However, the mechanisms through which this neuromodulation therapy engages spinal circuits remain enigmatic. Using computer simulations and behavioral experiments, we provide evidence that epidural electrical stimulation interacts with muscle spindle feedback circuits to modulate muscle activity during locomotion. Hypothesis-driven strategies emerging from simulations steered the design of stimulation protocols that adjust bilateral hindlimb kinematics throughout gait execution. These stimulation strategies corrected subject-specific gait and balance deficits in rats with incomplete and complete spinal cord injury. The conservation of muscle spindle feedback circuits across mammals suggests that the same mechanisms may facilitate motor control in humans. These results provide a conceptual framework to improve stimulation protocols for clinical applications. PMID- 26853303 TI - Epidermis-Derived Semaphorin Promotes Dendrite Self-Avoidance by Regulating Dendrite-Substrate Adhesion in Drosophila Sensory Neurons. AB - Precise patterning of dendritic arbors is critical for the wiring and function of neural circuits. Dendrite-extracellular matrix (ECM) adhesion ensures that the dendrites of Drosophila dendritic arborization (da) sensory neurons are properly restricted in a 2D space, and thereby facilitates contact-mediated dendritic self avoidance and tiling. However, the mechanisms regulating dendrite-ECM adhesion in vivo are poorly understood. Here, we show that mutations in the semaphorin ligand sema-2b lead to a dramatic increase in self-crossing of dendrites due to defects in dendrite-ECM adhesion, resulting in a failure to confine dendrites to a 2D plane. Furthermore, we find that Sema-2b is secreted from the epidermis and signals through the Plexin B receptor in neighboring neurons. Importantly, we find that Sema-2b/PlexB genetically and physically interacts with TORC2 complex, Tricornered (Trc) kinase, and integrins. These results reveal a novel role for semaphorins in dendrite patterning and illustrate how epidermal-derived cues regulate neural circuit assembly. PMID- 26853305 TI - Correlated Synaptic Inputs Drive Dendritic Calcium Amplification and Cooperative Plasticity during Clustered Synapse Development. AB - The mechanisms that instruct the assembly of fine-scale features of synaptic connectivity in neural circuits are only beginning to be understood. Using whole cell electrophysiology, two-photon calcium imaging, and glutamate uncaging in hippocampal slices, we discovered a functional coupling between NMDA receptor activation and ryanodine-sensitive intracellular calcium release that dominates the spatiotemporal dynamics of activity-dependent calcium signals during synaptogenesis. This developmentally regulated calcium amplification mechanism was tuned to detect and bind spatially clustered and temporally correlated synaptic inputs and enacted a local cooperative plasticity rule between coactive neighboring synapses. Consistent with the hypothesis that synapse maturation is spatially regulated, we observed clustering of synaptic weights in developing dendritic arbors. These results reveal developmental features of NMDA receptor dependent calcium dynamics and local plasticity rules that are suited to spatially guide synaptic connectivity patterns in emerging neural networks. PMID- 26853306 TI - Comprehensive Characterization of the Major Presynaptic Elements to the Drosophila OFF Motion Detector. AB - Estimating motion is a fundamental task for the visual system of sighted animals. In Drosophila, direction-selective T4 and T5 cells respond to moving brightness increments (ON) and decrements (OFF), respectively. Current algorithmic models of the circuit are based on the interaction of two differentially filtered signals. However, electron microscopy studies have shown that T5 cells receive their major input from four classes of neurons: Tm1, Tm2, Tm4, and Tm9. Using two-photon calcium imaging, we demonstrate that T5 is the first direction-selective stage within the OFF pathway. The four cells provide an array of spatiotemporal filters to T5. Silencing their synaptic output in various combinations, we find that all input elements are involved in OFF motion detection to varying degrees. Our comprehensive survey challenges the simplified view of how neural systems compute the direction of motion and suggests that an intricate interplay of many signals results in direction selectivity. PMID- 26853307 TI - Normothermic Perfusion of Donor Marginal Lungs With the Organ Care System Lung: Clinical and Morphologic Evaluation. PMID- 26853308 TI - Fluid Status Assessment and Management During the Perioperative Phase in Adult Cardiac Surgery Patients. PMID- 26853309 TI - Minocycline Effectively Protects the Rabbit's Spinal Cord From Aortic Occlusion Related Ischemia. AB - OBJECTIVES: To identify the minocycline anti-inflammatory and antiapoptotic mechanisms through which it is believed to exert spinal cord protection during aortic occlusion in the rabbit model. DESIGN: An animal model of aortic occlusion related spinal cord ischemia. Randomized study with a control group and pre ischemia and post-ischemia escalating doses of minocycline to high-dose minocycline in the presence of either hyperglycemia, a pro-apoptotic maneuver, or wortmannin, a specific phosphatidylinositol 3-kinase antagonist. SETTING: Tertiary medical center and school of medicine laboratory. PARTICIPANTS: Laboratory animals-rabbits. INTERVENTIONS: Balloon obstruction of infrarenal aorta introduced via femoral artery incision. RESULTS: Severe hindlimb paralysis (mean Tarlov score 0.36+/-0.81 out of 3) was observed in all the control group animals (9 of 11 with paraplegia and 2 of 11 with paraparesis) compared with 11 of 12 neurologically intact animals (mean Tarlov score 2.58+/-0.90 [p = 0.001 compared with control]) in the high-dose minocycline group. This protective effect was observed partially during a state of hyperglycemia and was completely abrogated by wortmannin. Minocycline administration resulted in higher neurologic scores (p = 0.003) and a shift to viable neurons and more apoptotic-stained nuclei resulting from reduced necrosis (p = 0.001). CONCLUSIONS: In a rabbit model of infrarenal aortic occlusion, minocycline effectively reduced paraplegia by increasing the number of viable neurons in a dose-dependent manner. Its action was completely abrogated by inhibiting the phosphatidylinositol 3-kinase pathway and was inhibited partially by the pro-apoptotic hyperglycemia maneuver, indicating that the activation of cell salvage pathways and mitochondrial sites are possible targets of minocycline action in an ischemic spinal cord. PMID- 26853311 TI - NICE guidance on psychological treatments for bipolar disorder: searching for the evidence. AB - The recent National Institute for Health and Care Excellence guidelines for bipolar disorder offer a number of recommendations for the psychological treatment of bipolar disorder. Scrutiny of the evidence on which these guidelines are based reveals significant flaws in the methodology and conduct of the relevant meta-analyses, and calls into question the interpretation of the evidence. PMID- 26853310 TI - External Tracheal Manipulation Maneuver (ETMM) to Facilitate Endobronchial Blocker Placement. PMID- 26853312 TI - Predictable swallowing function after open horizontal supraglottic partial laryngectomy. AB - OBJECTIVE: After horizontal supraglottic partial laryngectomy, patients have an increased risk of dysphagia as they are not able to close the laryngeal entrance during swallowing, especially if the surgical defect of the tongue base has increased. There is no investigation that studies risk factors for impaired swallow function, or that predicts postoperative swallow outcomes based on radiologically determined tumor dimensions. The present study investigated the impact of the tongue base tumor extension (determined by CT scan in patients undergoing partial laryngectomy) on the recovery rate of swallow function. METHODS: The retrospective study in a tertiary hospital between 2000 and 2015 included all patients who underwent open horizontal supraglottic partial laryngectomy due to oropharyngeal cancer of the tongue base, or supraglottic laryngeal cancer with tongue base infiltration. All clinicopathological data were collected. The dimension of tongue base infiltration was measured using CT scan. Swallow function was recorded by Fiberoptic Endoscopic Evaluation of Swallowing and determined by evaluating both the duration until nasogastric tube removal and changing of the cuffed tracheostomy tube for an uncuffed speech cannula. RESULTS: The study included 26 patients (44-76 years, median 59 years). The clinical tumor (cT) classification included cT2 and cT3, while the pathologic tumor (pT) classification included pT2 and pT3 in 90% and pT1 and pT4 in 10% respectively. The duration until using the speech cannula was not associated with clinicopathological data, including the investigated radiologic tumor dimensions (biggest tumor diameter, tongue base infiltration depth, width, height, area and volume). The duration until nasogastric tube removal was significantly associated with the tongue base infiltration width (p=0.012), height (p=0.026) and area (p<0.0001). The patients were divided into two groups according to the median tongue base infiltration area estimated as 6.20cm(2). In patients <6.20cm(2), 50% of the nasogastric tubes were removed after 4 days (95% CI 0-8.6 days) and in patients >=6.20cm(2), 50% were removed after 22 days (95% CI 6.8-37.2 days; p<0.0001). CONCLUSION: The postoperative swallow function after open horizontal supraglottic partial laryngectomy depends on the tumor extension of the tongue base. The tongue base infiltration area is a useful tool for surgical planning as it can be used to predict postoperative swallow function. In foreseeably permanent dysphagia, as well as permanent and necessary tracheotomy tube cuffs after organ-preserving surgery, alternative therapy methods should be particularly preferred as the primary chemoradiation. PMID- 26853313 TI - A simple approach to predict the stability of phospholipid vesicles to nebulization without performing aerosolization studies. AB - Membrane extrusion was investigated for predicting the stability of soya phosphatidylcholine liposomes and surfactosomes (Tween 80-enriched liposomes) to nebulization. Formulations were prepared with or without cholesterol, and salbutamol sulfate (SBS) or beclometasone dipropionate (BDP) were incorporated as model hydrophilic or hydrophobic drugs respectively. Formulations were extruded through 5, 2, 1 and 0.4 MUm polycarbonate membrane filters to study the influence of membrane pore size on drug retention by the vesicles. Surfactosomes were found to be very leaky to SBS, such that even without extrusion greater than 50% of the originally entrapped drug was lost; these losses were minimized by the inclusion of cholesterol. The smaller the membrane pore size, the greater the leakage of SBS; hence only around 10% were retained in cholesterol-free surfactosomes extruded through 0.4 MUm filters. To study the influence of vesicle size on SBS retained entrapment, an excessive extrusion protocol was proposed (51 extrusion cycles through 1 MUm filters) to compare the stability of freshly prepared vesicles (i.e. unextruded; median size approx. 4.5-6.5 MUm) with those previously extruded through 1 MUm pores. Cholesterol was essential for minimizing losses from liposomes, whilst for surfactosomes size reduction prior to extrusion was the only way to minimize SBS losses which reached up to 93.40% of the originally entrapped drug when no cholesterol was included. When extrusion was applied to BDP-loaded vesicles, greater proportions of the drug were retained in the vesicles compared to SBS. Even with extrusion through 0.4 MUm, BDP retention was around 50-60% with little effect of formulation. Excessive extrusion showed BDP retention using small liposomes (1 MUm) to be as high as 71-87%, compared to 50 66% for freshly prepared vesicles. The findings, based on extrusion, were compared to studies of vesicle stability to nebulization, published by a range of investigators. It was concluded that extrusion is a valid method for predicting the stability of liposomes to nebulization. PMID- 26853314 TI - Processing-induced-transformations (PITs) during direct compression: Impact of tablet composition and compression load on phase transition of caffeine. AB - In the pharmaceutical field, solid-state transitions that may occur during manufacturing of pharmaceuticals are of great importance. The phase transition of a model API, caffeine Form I (CFI), was studied during direct compression process by analysing the impacts of the operating conditions (process and formulation). This work is focused on two formulation parameters: nature of the diluent and impact of the caffeine dilution, and one process parameter: the compression pressure that may impact the phase transition of CFI. Tablets were made from pure CFI and from binary mixture of CFI/diluent (microcrystalline cellulose or anhydrous dicalcium phosphate). A kinetic study performed during six months helped to highlight the influence of these parameters on the CFI transition degree. Results showed a triggering effect of the direct compression process, transformation was higher in tablets than in uncompressed powders. Whatever the pressure applied, CFI transition degree was almost constant and uniformly occurring throughout the tablet volume. Nevertheless, several differences on the evolution of the CFI transition degree were observed between binary mixtures of CFI/diluent. An analysis of the transition mechanism with a stretched exponential law of the Johnson-Mehl-Avrami model shows that tableting accelerates the polymorphic transition without modifying its mechanism controlled by nucleation only. PMID- 26853315 TI - Investigation of cutaneous penetration properties of stearic acid loaded to dendritic core-multi-shell (CMS) nanocarriers. AB - Dendritic core-multi shell (CMS) particles are polymer based systems consisting of a dendritic polar polyglycerol polymer core surrounded by a two-layer shell of nonpolar C18 alkyl chains and hydrophilic polyethylene glycol. Belonging to nanotransport systems (NTS) they allow the transport and storage of molecules with different chemical characters. Their amphipihilic character CMS-NTS permits good solubility in aqueous and organic solutions. We showed by multifrequency electron paramagnetic resonance (EPR) spectroscopy that spin-labeled 5-doxyl stearic acid (5DSA) can be loaded into the CMS-NTS. Furthermore, the release of 5DSA from the carrier into the stratum corneum of porcine skin was monitored ex vivo by EPR spectroscopy. Additionally, the penetration of the CMS-NTS into the skin was analyzed by fluorescence microscopy using indocarbocyanine (ICC) covalently bound to the nanocarrier. Thereby, no transport into the viable skin was observed, whereas the CMS-NTS had penetrated into the hair follicles down to a depth of 340 MUm +/- 82 MUm. Thus, it could be shown that the combined application of fluorescence microscopy and multi-frequency EPR spectroscopy can be an efficient tool for investigating the loading of spin labeled drugs to nanocarrier systems, drug release and penetration into the skin as well as the localization of the NTS in the skin. PMID- 26853316 TI - Self-assembly PEGylation assists SLN-paclitaxel delivery inducing cancer cell apoptosis upon internalization. AB - In past years, a considerable progress has been made in the conversion of conventional chemotherapy into potent and safe nanomedicines. The ultimate goal is to improve the therapeutic window of current chemotherapeutics by reducing systemic toxicities and to deliver higher concentrations of the chemotherapeutic agents to malignant cells. In this work, we report that PEGylation of the nanocarriers increases drug intracellular bioavailability leading therefore to higher therapeutic efficacy. The surface of the already patented solid lipid nanoparticles (SLN) loaded with paclitaxel (SLN-PTX) was coated with a PEG layer (SLN-PTX_PEG) through an innovative process to provide stable and highly effective nanoparticles complying with the predefined pharmaceutical quality target product profile. We observed that PEGylation not only stabilizes the SLN, but also modulates their cellular uptake kinetics. As a consequence, the intracellular concentration of chemotherapeutics delivered by SLN-PTX_PEG increases. This leads to the increase of efficacy and thus it is expected to significantly circumvent cancer cell resistance and increase patient survival and cure. PMID- 26853317 TI - Use of crown ethers to isolate intermediates in ammonia-borane dehydrocoupling reactions. AB - The presence of 18-crown-6 in the Lewis acid-promoted dehydrocoupling reaction of ammonia borane permits isolation of [(THF)BH2NH3](+) and [BH2(NH3)2](+) cations. [(THF)BH2NH3](+) reacts with Lewis bases to give either boron adducts or by deprotonation at nitrogen to give borazine and ammonia-borane. PMID- 26853320 TI - Rationale and Prospects of Targeting Bacterial Two-component Systems for Antibacterial Treatment of Cystic Fibrosis Patients. AB - Bacterial respiratory infections are the main reason of morbidity and mortality among cystic fibrosis (CF) patients. In early childhood, the respiratory infections are due to Staphylococcus aureus and Haemophilus influenzae. In older CF patients, pathogenic Gram-negative bacteria like Achromobacter xylosoxidans, Burkholderia cepacia complex and especially Pseudomonas aeruginosa are more frequently seen. P. aeruginosa is a turning point in the respiratory disease in CF and its predominance increases with age. Bacteria use a variety of two component systems (TCS) to differentially express virulence factors involved in both acute and chronic infections. Here, we review bacterial TCS as targets for antibacterial treatment for CF patients. PMID- 26853321 TI - Functionalized Magnetic Nanostructures for Anticancer Therapy. AB - BACKGROUND: In the last years, the production and applications of nanoparticles based on iron oxides in the field of biomedicine presented a great interest due to their particular properties. Because of the expansion of the pharmaceutical industry numerous new systems for drugs delivery have appeared, and those centered on magnetic nanoparticles are in a particular attention and in different promising developmental stages. OBJECTIVE: In this mini review, some representative, interesting and feasible magnetic nanostructures obtained recently (from last 5-6 years) with possible use in antitumor/anticancer therapy are presented. RESULTS: The synthesis of these nanostructures with magnetic properties implies very simple assembling procedures and presents one of the lowest cytotoxic profiles. Magnetic nanostructures displayed possible appliance in a large diversity of biotechnological and medical fields, both for diagnose and therapy. CONCLUSION: Different types of magnetic nano-carriers loaded with different antitumor/anticancer agents and the cases tested in vivo are considered. PMID- 26853318 TI - Integrative systems and synthetic biology of cell-matrix adhesion sites. AB - The complexity of cell-matrix adhesion convolves its roles in the development and functioning of multicellular organisms and their evolutionary tinkering. Cell matrix adhesion is mediated by sites along the plasma membrane that anchor the actin cytoskeleton to the matrix via a large number of proteins, collectively called the integrin adhesome. Fundamental challenges for understanding how cell matrix adhesion sites assemble and function arise from their multi-functionality, rapid dynamics, large number of components and molecular diversity. Systems biology faces these challenges in its strive to understand how the integrin adhesome gives rise to functional adhesion sites. Synthetic biology enables engineering intracellular modules and circuits with properties of interest. In this review I discuss some of the fundamental questions in systems biology of cell-matrix adhesion and how synthetic biology can help addressing them. PMID- 26853319 TI - Cytochrome P450 20A1 in zebrafish: Cloning, regulation and potential involvement in hyperactivity disorders. AB - Cytochrome P450 (CYP) enzymes for which there is no functional information are considered "orphan" CYPs. Previous studies showed that CYP20A1, an orphan, is expressed in human hippocampus and substantia nigra, and in zebrafish (Danio rerio) CYP20A1 maternal transcript occurs in eggs, suggesting involvement in brain and in early development. Moreover, hyperactivity is reported in humans with chromosome 2 microdeletions including CYP20A1. We examined CYP20A1 in zebrafish, including impacts of chemical exposure on expression. Zebrafish CYP20A1 cDNA was cloned, sequenced, and aligned with cloned human CYP20A1 and predicted vertebrate orthologs. CYP20A1s share a highly conserved N-terminal region and unusual sequences in the I-helix and the heme-binding CYP signature motifs. CYP20A1 mRNA expression was observed in adult zebrafish organs including the liver, heart, gonads, spleen and brain, as well as the eye and optic nerve. Putative binding sites in proximal promoter regions of CYP20A1s, and response of zebrafish CYP20A1 to selected nuclear and xenobiotic receptor agonists, point to up-regulation by agents involved in steroid hormone response, cholesterol and lipid metabolism. There also was a dose-dependent reduction of CYP20A1 expression in embryos exposed to environmentally relevant levels of methylmercury. Morpholino knockdown of CYP20A1 in developing zebrafish resulted in behavioral effects, including hyperactivity and a slowing of the optomotor response in larvae. The results suggest that altered expression of CYP20A1 might be part of a mechanism linking methylmercury exposure to neurobehavioral deficits. The expanded information on CYP20A1 brings us closer to "deorphanization", that is, identifying CYP20A1 functions and its roles in health and disease. PMID- 26853323 TI - Recent Advancement and Technological Aspects of Pulsatile Drug Delivery System - A Laconic Review. AB - BACKGROUND: Pulsatile drug delivery system (PDDS) shows potential significance in the field of drug delivery to release the maximum amount of drug at a definite site and at specific time. PDDS are mainly time controlled delivery devices having a definite pause period for drug release, which is not affected by acidity, alkalinity, motility and enzymes present in the gastrointestinal tract. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. OBJECTIVE: The review article, discuss the general concepts, marketed formulations and patents or any other recent advancement in pulsatile release technology. It also highlights on diseases requiring therapy by pulsatile release, various researches on herbal pulsatile formulations and quality control aspects of PDDS. CONCLUSION: Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. PMID- 26853324 TI - Stimuli-responsive Smart Liposomes in Cancer Targeting. AB - BACKGROUND: Liposomes are vesicular carriers which possess aqueous core entrapped within the lipid bilayer. These are carriers of choice because of biocompatible and biodegradable features in addition to flexibility of surface modifications at surface and lipid compositions of lipid bilayers. OBJECTIVE: Liposomes have been reported well for cancer treatment using both passive and active targeting approaches however tumor microenvironment is still the biggest hurdle for safe and effective delivery of anticancer agents. To overcome this problem, stimuli responsive smart liposomes have emerged as promising cargoes pioneered to anomalous tumor milieu in response to pH, temperature, and enzymes etc. as internal triggers, and magnetic field, ultrasound, and redox potential as external guides for enhancement of drug delivery to tumors. CONCLUSION: This review focuses on all such stimuli-responsive approaches using fabrication potentiality of liposomes in combination to various ligands, linkers, and PEGylation etc. Scientists engaged in cancer targeting approaches can get benefited greatly with this knowledgeable assemblage of advances in liposomal nanovectors. PMID- 26853322 TI - Virological and Clinical Response to Interferon-Free Regimens in Patients with HCV-Related Mixed Cryoglobulinemia: Preliminary Results of a Prospective Pilot Study. AB - Mixed Cryoglobulinemia (MC) is the most frequent extrahepatic manifestation of Hepatitis C virus (HCV) infection. MC is an autoimmune /B-cell lymphoproliferative disorder characterized by circulating immune-complexes, named cryoglobulins. MC patients exhibit symptoms due to a systemic vasculitis of small/medium size vessels (mixed cryoglobulinemia syndrome, MCS) in a percentage going from 5 to 30%. The first-line therapeutic option in MCS patients is the etiologic treatment and, in the past fifteen years, antiviral therapy with Pegylated-Interferon (Peg-IFN) plus Ribavirin (RBV) represented the standard of care. Lately, the arrival of direct acting antivirals (DAAs) significantly modified the cure of HCV infection, consenting the use of IFN-free regimens. Here we report a review of the literature about the role of antiviral treatment, following its evolution, in treating HCVrelated MC. Furthermore, we report the results, after 8 weeks of treatment, of a preliminary pilot prospective study, counting 17 patients with HCV-related MC with or without MCS, treated with new generation DAAs in IFN-free regimens. After 8 weeks of DAA administration, all the subjects were HCV RNA negative. Moreover, in 6/17 (35%) patients cryoglobulins disappeared and, on the whole, in all patients a decrease of the cryocrit values was observed (p<0.05). Furthermore, three MCS-HCV patients (30%) resulted to be complete clinical responders and 5 subjects (50%) partial clinical responders. Therefore, IFN-free anti-HCV treatment appears to be safe and effective in MC patients from virological and clinical points of view, thus supporting the importance of HCV eradication in leading MC remission. PMID- 26853325 TI - A Pilot Placebo Controlled Randomized Trial of Dexamethasone for Chronic Subdural Hematoma. AB - BACKGROUND: Current opinions regarding the use of dexamethasone in the treatment of chronic subdural hematomas (CSDH) are only based on observational studies. Moreover, the use of corticosteroids in asymptomatic or minimally symptomatic patient with this condition remains controversial. Here, we present data from a prospective randomized pilot study of CSDH patients treated with dexamethasone or placebo. METHODS: Twenty patients with imaging-confirmed CSDH were recruited from a single center and randomized to receive dexamethasone (12 mg/day for 3 weeks followed by tapering) or placebo as a conservative treatment. Patients were followed for 6 months and the rate of success of conservative treatment with dexamethasone versus placebo was measured. Parameters such as hematoma thickness and clinical changes were also compared before and after treatment with chi square tests. Adverse events and complications were documented. RESULTS: During the 6-month follow-up, one of ten patients treated with corticosteroids had to undergo surgical drainage and three of ten patients were treated surgically after placebo treatment. At the end of the study, all remaining patients had complete radiological resolution. No significant differences were observed in terms of hematoma thickness profile and impression of change; however, patients experienced more severe side effects when treated with steroids as compared with placebo. Dexamethasone contributed to many serious adverse events. CONCLUSIONS: Given the small sample size, these preliminary results have not shown a clear beneficial effect of dexamethasone against placebo in our patients. However, the number of secondary effects reported was much greater for corticosteroids, and dexamethasone treatment was responsible for significant complications. PMID- 26853326 TI - Detection and quantification of RNA 2'-O-methylation and pseudouridylation. AB - RNA-guided RNA modification is a naturally occurring process that introduces 2'-O methylation and pseudouridylation into rRNA, spliceosomal snRNA and several other types of RNA. The Box C/D ribonucleoproteins (RNP) and Box H/ACA RNP, each containing one unique guide RNA (Box C/D RNA or Box H/ACA RNA) and a set of core proteins, are responsible for 2'-O-methylation and pseudouridylation respectively. Box C/D RNA and Box H/ACA RNA provide the modification specificity through base pairing with their RNA substrate. These post-transcriptional modifications could profoundly alter the properties and functions of substrate RNAs. Thus it is desirable to establish reliable and standardized modification methods to study biological functions of modified nucleotides in RNAs. Here, we present several sensitive and efficient methods and protocols for detecting and quantifying post-transcriptional 2'-O-methylation and pseudouridylation. PMID- 26853327 TI - Characterizing 3D RNA structure by single molecule FRET. AB - The importance of elucidating the three dimensional structures of RNA molecules is becoming increasingly clear. However, traditional protein structural techniques such as NMR and X-ray crystallography have several important drawbacks when probing long RNA molecules. Single molecule Forster resonance energy transfer (smFRET) has emerged as a useful alternative as it allows native sequences to be probed in physiological conditions and allows multiple conformations to be probed simultaneously. This review serves to describe the method of generating a three dimensional RNA structure from smFRET data from the biochemical probing of the secondary structure to the computational refinement of the final model. PMID- 26853328 TI - Effects of erythropoietin on systemic hematocrit and oxygen transport in the splenectomized horse. AB - To test the hypotheses that erythropoietin (rhuEPO) treatment increases systemic hematocrit, maximal O2 uptake (VO2max, by elevated perfusive and diffusive O2 conductances) and performance five female horses (4-13 years) received 15 IU/kg rhuEPO (erythropoietin) three times per week for three weeks. These horses had been splenectomized over 1 year previously to avoid confounding effects from the mobilization of splenic red blood cell reserves. Each horse performed three maximal exercise tests (one per month) on an inclined (4 degrees ) treadmill to the limit of tolerance; two control trials and one following EPO treatment. Measurements of hemoglobin concentration ([Hb] and hematocrit), plasma and blood volume, VO2, cardiac output as well as arterial and mixed venous blood gases were made at rest and during maximal exercise. EPO increased resting [Hb] by 18% from 13.3 +/- 0.6 to 15.7 +/- 0.8 g/dL (mean +/- SD) corresponding to an increased hematocrit from 36 +/- 2 to 46 +/- 2% concurrent with 23 and 10% reductions in plasma and blood volume, respectively (all P<0.05). EPO elevated VO2max by 20% from 25.7 +/- 1.7 to 30.9 +/- 3.4 L/min (P<0.05) via a 17% increase in arterial O2 content and 18% greater arteriovenous O2 difference in the face of an unchanged cardiac output. To achieve the greater VO2max after EPO, diffusive O2 conductance increased ~ 30% (from 580 +/- 76 to 752 +/- 166 mL O2/mmHg/min, P<0.05) which was substantially greater than the elevation of perfusive O2 conductance. These effects of EPO were associated with an increased exercise performance (total running time: control, 216 +/- 72; EPO, 264 +/- 48 s, P<0.05). We conclude that EPO substantially increases VO2max and performance in the splenectomized horse via improved perfusive and diffusive O2 transport. PMID- 26853329 TI - Effects of different ratios of pig manure to fungus residue on physicochemical parameters during composting. AB - This study examined physicochemical parameters to assess their effectiveness as stability and maturity indicators during the process of composting pig manure and fungus residue at different ratios. The results showed that composting mixtures with all ratios of pig manure to fungus residue maintained a temperature exceeding 50 degrees C for more than 10 days during composting and met the requirement for pathogen destruction. The treatment containing mainly pig manure showed higher nitrogen loss and a shorter thermophilic phase and maturity time than the treatment containing mainly fungus residue. The germination index (GI) values indicated that compost maturity was achieved in the final compost with initial ratios of pig manure to fungus residue of 9:1-7:3 (GIs of 101.4%, 91.2%, and 81.3%); the ratio of 6:4 did not reach compost maturity (GI of 63.8%) and had an inhibitory effect on seed germination. The results of this study suggest that a ratio of pig manure to fungus residue of approximately 8:2 can be considered suitable for the efficient and quality composting of pig manure and fungus residue. IMPLICATIONS: Co-composting of pig manure and edible fungi residue with appropriate proportion can effectively reduce the risk of environmental pollution caused by agricultural wastes, as well as achieve a safer and high-quality organic fertilizer, which can be used to improve physical and chemical properties of the soil, increase crop yields, and promote agricultural sustainable development. Therefore, technique of co-composting of pig manure and edible fungi residue has a wide prospect of application in practical production all over the world. PMID- 26853330 TI - The Multidisciplinary Approach Needs to Extend Into Head and Neck Cancer Clinical Trials. PMID- 26853331 TI - A Time for Optimism? The State of Radiation Oncology in Iran. PMID- 26853332 TI - Results of the 2013-2015 Association of Residents in Radiation Oncology Survey of Chief Residents in the United States. AB - PURPOSE: The purpose of this project was to survey radiation oncology chief residents to define their residency experience and readiness for independent practice. METHODS AND MATERIALS: During the academic years 2013 to 2014 and 2014 to 2015, the Association of Residents in Radiation Oncology (ARRO) conducted an electronic survey of post-graduate year-5 radiation oncology residents in the United States during the final 3 months of training. Descriptive statistics are reported. RESULTS: Sixty-six chief residents completed the survey in 2013 to 2014 (53% response rate), and 69 completed the survey in 2014 to 2015 (64% response rate). Forty to 85% percent of residents reported inadequate exposure to high dose rate and low-dose rate brachytherapy. Nearly all residents in both years (>90%) reported adequate clinical experience for the following disease sites: breast, central nervous system, gastrointestinal, genitourinary, head and neck, and lung. However, as few as 56% reported adequate experience in lymphoma or pediatric malignancies. More than 90% of residents had participated in retrospective research projects, with 20% conducting resident-led prospective clinical trials and 50% conducting basic science or translational projects. Most chief residents reported working 60 or fewer hours per week in the clinical/hospital setting and performing fewer than 15 hours per week tasks that were considered to have little or no educational value. There was more than 80% compliance with Accreditation Council for Graduate Medical Education (ACGME) work hour limits. Fifty-five percent of graduating residents intended to join an established private practice group, compared to 25% who headed for academia. Residents perceive the job market to be more competitive than previous years. CONCLUSIONS: This first update of the ARRO chief resident survey since the 2007 to 2008 academic year documents US radiation oncology residents' experiences and conditions over a 2-year period. This analysis may serve as a valuable tool for those seeking to improve training of the next generation of oncology leaders. PMID- 26853333 TI - Role of Surgical Versus Clinical Staging in Chemoradiated FIGO Stage IIB-IVA Cervical Cancer Patients-Acute Toxicity and Treatment Quality of the Uterus-11 Multicenter Phase III Intergroup Trial of the German Radiation Oncology Group and the Gynecologic Cancer Group. AB - PURPOSE: The Uterus-11 trial was designed to evaluate the role of surgical staging in patients with cervical cancer before primary chemoradiation therapy (CRT). The present report provides the toxicity data stratified by the treatment arm and technique. METHODS AND MATERIALS: A total of 255 patients with carcinoma of the uterine cervix (International Federation of Gynecology and Obstetrics stage IIB-IVA) were randomized to either surgical staging followed by CRT (arm A) or clinical staging followed by CRT (arm B). Patients with para-aortic metastases underwent extended field radiation therapy (RT). Brachytherapy was mandatory. The present report presents the acute therapy-related toxicities stratified by treatment arm and radiation technique. RESULTS: A total of 240 patients were eligible (n=121 in arm A; n=119 in arm B). Of the 240 patients, 236 (98.3%) underwent external beam RT with a median total dose of 50.4 Gy. The mean treatment duration was 53 days. Of the patients, 60% underwent intensity modulated RT (IMRT). A total of 234 patients (97.5%) underwent chemotherapy, and 231 (96.3%) underwent brachytherapy, with a median single dose of 6 Gy covering the tumor to a median nominal total dose of 28 Gy. Treatment was well tolerated, with 0% grade >=3 genitourinary and gastrointestinal toxicity, 6% grade 3 nausea, 3% grade 3 vomiting, and <2% grade 3 diarrhea. More patients after surgical staging experienced grade 2 anemia (54.3% in arm A vs 45.3% in arm B; P=.074) and grade 2 leukocytopenia (41.4% vs 31.6%; P=.56). Of the patients who received IMRT versus a 3-dimensional technique, 65.3% versus 33.7% presented with grade 2 anemia. Grade 3 gastrointestinal and grade 2 bladder toxicity were significantly reduced with the use of IMRT. CONCLUSIONS: The incidence and severity of acute therapy-related toxicity compared favorably with those from other randomized trials. Excellent adherence to treatment and treatment quality was achieved compared with patterns of care analyses. Surgical staging led to a doubled number of patients treated with extended field RT. The question of whether surgical staging is beneficial in the context of primary CRT requires further study. PMID- 26853335 TI - Nodal Clearance Rate and Long-Term Efficacy of Individualized Sentinel Node-Based Pelvic Intensity Modulated Radiation Therapy for High-Risk Prostate Cancer. AB - PURPOSE: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement - n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients. METHODS AND MATERIALS: Data on 475 high-risk prostate cancer patients were examined. Sixty one consecutive patients received pelvic SN-based IMRT (5 * 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 * 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN-pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapy sample. Biochemical control and overall survival were estimated for the SN-IMRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostate-specific antigen, and T category in the radiation therapy sample. RESULTS: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation. CONCLUSIONS: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose escalation strategies to the prostate in a larger prospective series. PMID- 26853336 TI - Moderate Hypofractionated Protracted Radiation Therapy and Dose Escalation for Prostate Cancer: Do Dose and Overall Treatment Time Matter? AB - PURPOSE: This was a retrospective study of 2 sequential dose escalation regimens of twice-weekly 4 Gy/fractions hypofractionated intensity modulated radiation therapy (IMRT): 56 Gy and 60 Gy delivered within a protracted overall treatment time (OTT) of 6.5 and 7 weeks, respectively. METHODS AND MATERIALS: 163 prostate cancer patients with cT1c-T3a disease and nodal involvement risk <=20% (Roach index) were treated twice weekly to the prostate +/- seminal vesicles with 2 sequential dose-escalated IMRT schedules: 56 Gy (14 * 4 Gy, n=81) from 2003 to 2007 and 60 Gy (15 * 4 Gy, n=82) from 2006 to 2010. Patient repositioning was made with bone matching on portal images. Gastrointestinal (GI) and genitourinary (GU) toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0 grading scale. RESULTS: There were no significant differences regarding the acute GU and GI toxicities in the 2 dose groups. The median follow-up times were 80.2 months (range, 4.5-121 months) and 56.5 months (range, 1.4-91.2 months) for patients treated to 56 and 60 Gy, respectively. The 5-year grade >=2 late GU toxicity-free survivals with 56 Gy and 60 Gy were 96 +/- 2.3% and 78.2 +/- 5.1% (P=.001), respectively. The 5-year grade >=2 late GI toxicity-free survivals with 56 Gy and 60 Gy were 98.6 +/- 1.3% and 85.1 +/- 4.5% (P=.005), respectively. Patients treated with 56 Gy showed a 5-year biochemical progression-free survival (bPFS) of 80.8 +/- 4.7%, worse than patients treated with 60 Gy (93.2 +/- 3.9%, P=.007). A trend for a better 5-year distant metastasis-free survival was observed among patients treated in the high-dose group (95.3 +/- 2.7% vs 100%, P=.073, respectively). On multivariate analysis, only the 60-Gy group predicted for a better bPFS (P=.016, hazard ratio = 4.58). CONCLUSIONS: A single 4-Gy additional fraction in patients treated with a hypofractionated protracted IMRT schedule of 14 * 4 Gy resulted in a similar and minimal acute toxicity, in worse moderate to severe urinary and GI late effects, but a significantly better biochemical control. PMID- 26853334 TI - Very High-Risk Localized Prostate Cancer: Outcomes Following Definitive Radiation. AB - PURPOSE: Existing definitions of high-risk prostate cancer consist of men who experience significant heterogeneity in outcomes. As such, criteria that identify a subpopulation of National Comprehensive Cancer Network (NCCN) high-risk prostate cancer patients who are at very high risk (VHR) for poor survival outcomes following prostatectomy were recently developed at our institution and include the presence of any of the following disease characteristics: multiple NCCN high-risk factors, primary Gleason pattern 5 disease and/or >=5 biopsy cores with Gleason sums of 8 to 10. Whether these criteria also apply to men undergoing definitive radiation is unclear, as is the optimal treatment regimen in these patients. METHODS AND MATERIALS: All men consecutively treated with definitive radiation by a single provider from 1993 to 2006 and who fulfilled criteria for NCCN high-risk disease were identified (n=288), including 99 patients (34%) with VHR disease. Multivariate-adjusted competing risk regression models were constructed to assess associations between the VHR definition and biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM). Multivariate-adjusted Cox regression analysis assessed the association of the VHR definition with overall mortality (OM). Cumulative incidences of failure endpoints were compared between VHR men and other NCCN high-risk men. RESULTS: Men with VHR disease compared to other NCCN high-risk men experienced a higher 10 year incidence of BF (54.0% vs 35.4%, respectively, P<.001), DM (34.9% vs 13.4%, respectively, P<.001), PCSM (18.5% vs 5.9%, respectively, P<.001), and OM (36.4% vs 27.0%, respectively, P=.04). VHR men with a detectable prostate-specific antigen (PSA) concentration at the end of radiation (EOR) remained at high risk of 10-year PCSM compared to VHR men with an undetectable EOR PSA (31.0% vs 13.7%, respectively, P=.05). CONCLUSIONS: NCCN high-risk prostate cancer patients who meet VHR criteria experience distinctly worse outcomes following definitive radiation and long-term androgen deprivation therapy, particularly if an EOR PSA is detectable. Optimal use of local therapies for VHR patients should be explored further, as should novel agents. PMID- 26853337 TI - What Aspects of Personal Care Are Most Important to Patients Undergoing Radiation Therapy for Prostate Cancer? AB - PURPOSE/OBJECTIVE: The overall quality of patient care is a function of the quality of both its technical and its nontechnical components. The purpose of this study was to identify the elements of nontechnical (personal) care that are most important to patients undergoing radiation therapy for prostate cancer. METHODS AND MATERIALS: We reviewed the literature and interviewed patients and health professionals to identify elements of personal care pertinent to patients undergoing radiation therapy for prostate cancer. We identified 143 individual elements relating to 10 aspects of personal care. Patients undergoing radical radiation therapy for prostate cancer completed a self-administered questionnaire in which they rated the importance of each element. The overall importance of each element was measured by the percentage of respondents who rated it as "very important." The importance of each aspect of personal care was measured by the mean importance of its elements. RESULTS: One hundred eight patients completed the questionnaire. The percentage of patients who rated each element "very important" ranged from 7% to 95% (mean 61%). The mean importance rating of the elements of each aspect of care varied significantly: "perceived competence of caregivers," 80%; "empathy and respectfulness of caregivers," 67%; "adequacy of information sharing," 67%; "patient centeredness," 59%; "accessibility of caregivers," 57%; "continuity of care," 51%; "privacy," 51%; "convenience," 45%; "comprehensiveness of services," 44%; and "treatment environment," 30% (P<.0001). Neither age nor education was associated with importance ratings, but the patient's health status was associated with the rating of some elements of care. CONCLUSIONS: Many different elements of personal care are important to patients undergoing radiation therapy for prostate cancer, but the 3 aspects of care that most believe are most important are these: the perceived competence of their caregivers, the empathy and respectfulness of their caregivers, and the adequacy of information sharing. PMID- 26853338 TI - Dose-Dependent Cortical Thinning After Partial Brain Irradiation in High-Grade Glioma. AB - PURPOSE: Radiation-induced cognitive deficits may be mediated by tissue damage to cortical regions. Volumetric changes in cortex can be reliably measured using high-resolution magnetic resonance imaging (MRI). We used these methods to study the association between radiation therapy (RT) dose and change in cortical thickness in high-grade glioma (HGG) patients. METHODS AND MATERIALS: We performed a voxel-wise analysis of MRI from 15 HGG patients who underwent fractionated partial brain RT. Three-dimensional MRI was acquired pre- and 1 year post RT. Cortex was parceled with well-validated segmentation software. Surgical cavities were censored. Each cortical voxel was assigned a change in cortical thickness between time points, RT dose value, and neuroanatomic label by lobe. Effects of dose, neuroanatomic location, age, and chemotherapy on cortical thickness were tested using linear mixed effects (LME) modeling. RESULTS: Cortical atrophy was seen after 1 year post RT with greater effects at higher doses. Estimates from LME modeling showed that cortical thickness decreased by 0.0033 mm (P<.001) for every 1-Gy increase in RT dose. Temporal and limbic cortex exhibited the largest changes in cortical thickness per Gy compared to that in other regions (P<.001). Age and chemotherapy were not significantly associated with change in cortical thickness. CONCLUSIONS: We found dose-dependent thinning of the cerebral cortex, with varying neuroanatomical regional sensitivity, 1 year after fractionated partial brain RT. The magnitude of thinning parallels 1-year atrophy rates seen in neurodegenerative diseases and may contribute to cognitive decline following high-dose RT. PMID- 26853340 TI - Fluorodeoxyglucose Uptake on Positron Emission Tomography Is a Useful Predictor of Long-Term Pain Control After Palliative Radiation Therapy in Patients With Painful Bone Metastases: Results of a Single-Institute Prospective Study. AB - PURPOSE: To determine whether fluorodeoxyglucose positron emission tomography (FDG-PET) before and after palliative radiation therapy (RT) can predict long term pain control in patients with painful bone metastases. METHODS AND MATERIALS: Thirty-one patients with bone metastases who received RT were prospectively included. Forty painful metastatic treatment fields were evaluated. All patients had undergone pre-RT and post-RT PET/CT scanning. We evaluated the relationships between the pre-RT, post-RT, and changes in maximum standardized uptake value (SUVmax) and the pain response, and between SUVmax and pain relapse of the bone metastases in the treatment field. In addition, we compared the SUVmax according to the length of time from the completion of RT to pain relapse of the bone metastases. RESULTS: Regarding the pain response at 4 weeks after the completion of RT, there were 36 lesions of 27 patients in the responder group and 4 lesions of 4 patients in the nonresponder group. Changes in the SUVmax differed significantly between the responder and nonresponder groups in both the early and delayed phases (P=.0292 and P=.0139, respectively), but no relationship was observed between the pre-RT and post-RT SUVmax relative to the pain response. The responder group was evaluated for the rate of relapse. Thirty-five lesions of 26 patients in the responder group were evaluated, because 1 patient died of acute renal failure at 2 months after RT. Twelve lesions (34%) showed pain relapse, and 23 lesions (66%) did not. There were significant differences between the relapse and nonrelapse patients in terms of the pre-RT (early/delayed phases: P<.0001/P<.0001), post-RT (P=.0199/P=.0261), and changes in SUVmax (P=.0004/P=.004). CONCLUSIONS: FDG-PET may help predict the outcome of pain control in the treatment field after palliative RT for painful bone metastases. PMID- 26853339 TI - Gemcitabine Plus Radiation Therapy for High-Grade Glioma: Long-Term Results of a Phase 1 Dose-Escalation Study. AB - PURPOSE: To evaluate the tolerability and efficacy of gemcitabine plus radiation therapy (RT) in this phase 1 study of patients with newly diagnosed malignant glioma (HGG). PATIENTS AND METHODS: Between 2004 and 2012, 29 adults with HGG were enrolled. After any extent of resection, RT (60 Gy over 6 weeks) was given concurrent with escalating doses of weekly gemcitabine. Using a time-to-event continual reassessment method, 5 dose levels were evaluated starting at 500 mg/m(2) during the last 2 weeks of RT and advanced stepwise into earlier weeks. The primary objective was to determine the recommended phase 2 dose of gemcitabine plus RT. Secondary objectives included progression-free survival, overall survival (OS), and long-term toxicity. RESULTS: Median follow-up was 38.1 months (range, 8.9-117.5 months); 24 patients were evaluable for toxicity. After 2005 when standard practice changed, patients with World Health Organization grade 4 tumors were no longer enrolled. Median progression-free survival for 22 patients with grade 3 tumors was 26.0 months (95% confidence interval [CI] 15.6 inestimable), and OS was 48.5 months (95% CI 26.8-inestimable). In 4 IDH mutated, 1p/19q codeleted patients, no failures occurred, with all but 1 alive at time of last follow-up. Seven with IDH mutated, non-codeleted tumors with ATRX loss had intermediate OS of 73.5 months (95% CI 32.8-inestimable). Six nonmutated, non codeleted patients had a median OS of 26.5 months (95% CI 25.4-inestimable). The recommended phase 2 dose of gemcitabine plus RT was 750 mg/m(2)/wk given the last 4 weeks of RT. Dose reductions were most commonly due to grade 3 neutropenia; no grade 4 or 5 toxicities were seen. CONCLUSIONS: Gemcitabine concurrent with RT is well-tolerated and yields promising outcomes, including in patients with adverse molecular features. It is a candidate for further study, particularly for poor prognosis patient subgroups with HGG. PMID- 26853341 TI - Resistance Exercise and Inflammation in Breast Cancer Patients Undergoing Adjuvant Radiation Therapy: Mediation Analysis From a Randomized, Controlled Intervention Trial. AB - PURPOSE: To explore the mediating role of inflammatory parameters in the development of fatigue, pain, and potentially related depressive symptoms during radiation therapy for breast cancer and its mitigation by resistance exercise. METHODS AND MATERIALS: Breast cancer patients scheduled for adjuvant radiation therapy were randomized to 12-week progressive resistance exercise training (EX) or a relaxation control group. Interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) were measured in serum samples collected before, at the end, and 6 weeks after radiation therapy from 103 chemotherapy-naive participants. Fatigue was assessed with the multidimensional Fatigue Assessment Questionnaire, pain with the European Organization for Research and Treatment of Cancer QLQ-C30, and depressive symptoms with the Center for Epidemiologic Studies Depression Scale. Analysis of covariance models, partial correlations, Freedman-Schatzkin tests, and R(2) effect-size measures for mediation were calculated. RESULTS: The analysis of covariance models revealed a significant intervention effect on IL-6 (P=.010) and the IL-6/IL-1ra ratio (P=.018), characterized by a marked increase during radiation therapy among controls, but no significant change in EX. Interleukin-1 receptor antagonist did not change significantly in either group (P=.88). Increased IL-6 and IL-6/IL-1ra levels at the end of radiation therapy were significantly associated with increased physical fatigue and pain 6 weeks after radiation. We observed significant partial mediation by IL-6 and IL-6/IL 1ra of the effect of resistance exercise on physical fatigue (Freedman-Schatzkin P=.023 and P<.001) and pain (both P<.001). Hereby IL-6 and IL-6/IL-1ra mediated between 15% and 24% of the variance of physical fatigue and pain explained by the intervention. CONCLUSIONS: This randomized, controlled trial showed a significantly increased proinflammatory cytokine level after adjuvant radiation therapy in breast cancer patients. This effect was counteracted by progressive resistance exercise training. Interleukin-6 and the IL-6/IL-1ra ratio seemed to mediate the beneficial effect of exercise on physical fatigue and pain but only to a small extent. PMID- 26853342 TI - Practical Implications of the Publication of Consensus Guidelines by the American Society for Radiation Oncology: Accelerated Partial Breast Irradiation and the National Cancer Data Base. AB - PURPOSE: To examine utilization trends of accelerated partial breast irradiation (APBI) in the American College of Surgeons' National Cancer Database and changes in APBI use after the 2009 publication of the American Society for Radiation Oncology (ASTRO) guidelines. METHODS AND MATERIALS: A total of 399,705 women were identified who were diagnosed from 2004 to 2011 with nonmetastatic invasive breast cancer or ductal carcinoma in situ who were treated with breast-conserving surgery and radiation therapy to the breast. Patients were divided by the type of treatment received (whole breast irradiation or APBI) and by suitability to receive APBI as defined by the ASTRO guidelines. Logistic regression was applied to study APBI use overall and within guideline categorization, and a multivariable model was created to determine predictors of treatment with brachytherapy-based APBI based on guideline categorization. RESULTS: For all patients, APBI use increased, from 3.8% in 2004 to 10.6% in 2011 (P<.0001). Overall rates of APBI utilization were higher among "suitable" than "cautionary"/"unsuitable" patients (14.8% vs 7.1%, P<.0001). The majority of APBI treatment was delivered using brachytherapy, for which use peaked in 2008. Starting in 2009, among "suitable" patients, utilization of APBI via brachytherapy plateaued, whereas for "cautionary"/"unsuitable" patients, treatment with brachytherapy-based APBI declined and then plateaued. CONCLUSION: Use of APBI across all patient groups increased from 2004 through 2008. After publication of the ASTRO APBI guidelines in 2009, rates of brachytherapy-based APBI treatment plateaued among "suitable" patients and declined and then plateaued among "cautionary"/"unsuitable" patients. Our study highlights how large national databases can be used to assess national trends in radiation use in response to the publication of guidelines. PMID- 26853343 TI - Factors Influencing Pulmonary Toxicity in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in the Setting of Total Body Irradiation Based Myeloablative Conditioning. AB - PURPOSE: This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), followed by allogeneic hematopoietic stem cell transplantation (HSCT). METHODS AND MATERIALS: The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified using clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period. RESULTS: PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS. CONCLUSIONS: A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly influenced IPS. TBI dose rate is a contributing factor influencing pulmonary toxicity and rates less than 15 cGy/min should be considered to decrease the risk of IPS. PMID- 26853344 TI - Variation in Definitive Therapy for Localized Non-Small Cell Lung Cancer Among National Comprehensive Cancer Network Institutions. AB - PURPOSE: This study determined practice patterns in the staging and treatment of patients with stage I non-small cell lung cancer (NSCLC) among National Comprehensive Cancer Network (NCCN) member institutions. Secondary aims were to determine trends in the use of definitive therapy, predictors of treatment type, and acute adverse events associated with primary modalities of treatment. METHODS AND MATERIALS: Data from the National Comprehensive Cancer Network Oncology Outcomes Database from 2007 to 2011 for US patients with stage I NSCLC were used. Main outcome measures included patterns of care, predictors of treatment, acute morbidity, and acute mortality. RESULTS: Seventy-nine percent of patients received surgery, 16% received definitive radiation therapy (RT), and 3% were not treated. Seventy-four percent of the RT patients received stereotactic body RT (SBRT), and the remainder received nonstereotactic RT (NSRT). Among participating NCCN member institutions, the number of surgeries-to-RT course ratios varied between 1.6 and 34.7 (P<.01), and the SBRT-to-NSRT ratio varied between 0 and 13 (P=.01). Significant variations were also observed in staging practices, with brain imaging 0.33 (0.25-0.43) times as likely and mediastinoscopy 31.26 (21.84 44.76) times more likely for surgical patients than for RT patients. Toxicity rates for surgical and for SBRT patients were similar, although the rates were double for NSRT patients. CONCLUSIONS: The variations in treatment observed among NCCN institutions reflects the lack of level I evidence directing the use of surgery or SBRT for stage I NSCLC. In this setting, research of patient and physician preferences may help to guide future decision making. PMID- 26853345 TI - Potential Use of (18)F-fluorodeoxyglucose Positron Emission Tomography-Based Quantitative Imaging Features for Guiding Dose Escalation in Stage III Non-Small Cell Lung Cancer. AB - PURPOSE: To determine whether previously identified quantitative image features (QIFs) based on (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) (co-occurrence matrix energy and solidity) are able to isolate subgroups of patients who would receive a benefit or detriment from dose escalation in terms of overall survival (OS) or progression-free survival (PFS). METHODS AND MATERIALS: Subgroups of a previously analyzed 225 patient cohort were generated with the use of 5-percentile increment cutoff values of disease solidity and primary tumor co-occurrence matrix energy. The subgroups were analyzed with a log rank test to determine whether there was a difference in OS and PFS between patients treated with 60 to 70 Gy and those receiving 74 Gy. RESULTS: In the entire patient cohort, there was no statistical difference in terms of OS or PFS between patients receiving 74 Gy and those receiving 60 to 70 Gy. It was qualitatively observed that as disease solidity and primary co-occurrence matrix energy increased, patients receiving 74 Gy had an improved OS and PFS compared with those receiving 60 to 70 Gy. The opposite trend (detriment of receiving 74 Gy) was also observed regarding low values of disease solidity and primary co occurrence matrix energy. CONCLUSIONS: FDG-PET-based QIFs were found to be capable of isolating subgroups of patients who received a benefit or detriment from dose escalation. PMID- 26853347 TI - Depigmentation Within the Radiation Field in Patients With Vitiligo. PMID- 26853346 TI - Imaging and Data Acquisition in Clinical Trials for Radiation Therapy. AB - Cancer treatment evolves through oncology clinical trials. Cancer trials are multimodal and complex. Assuring high-quality data are available to answer not only study objectives but also questions not anticipated at study initiation is the role of quality assurance. The National Cancer Institute reorganized its cancer clinical trials program in 2014. The National Clinical Trials Network (NCTN) was formed and within it was established a Diagnostic Imaging and Radiation Therapy Quality Assurance Organization. This organization is Imaging and Radiation Oncology Core, the Imaging and Radiation Oncology Core Group, consisting of 6 quality assurance centers that provide imaging and radiation therapy quality assurance for the NCTN. Sophisticated imaging is used for cancer diagnosis, treatment, and management as well as for image-driven technologies to plan and execute radiation treatment. Integration of imaging and radiation oncology data acquisition, review, management, and archive strategies are essential for trial compliance and future research. Lessons learned from previous trials are and provide evidence to support diagnostic imaging and radiation therapy data acquisition in NCTN trials. PMID- 26853349 TI - Erratum. Radiation sensitivity and radiation necrosis in the short telomere syndromes. PMID- 26853350 TI - In Regard to Bland et al. PMID- 26853353 TI - Out of the Blue! Azuliporphyrins and Related Carbaporphyrinoid Systems. AB - First reported in 1997, azuliporphyrins have proven to be a truly remarkable family of porphyrin analogues. In this system, although the porphyrin framework is retained, one of the pyrrolic moieties has been replaced by an azulene unit. Azulene favors electrophilic substitution at the 1,3-positions, which are structurally analogous to the alpha-positions in pyrrole, and this property facilitates the construction of azulene-containing porphyrinoid systems. Azuliporphyrins were first prepared from tripyrranes and 1,3 azulenedicarbaldehyde using a "3 + 1" variant on the MacDonald reaction. Subsequently, azulenes were shown to react with acetoxymethylpyrroles under acidic conditions to generate azulitripyrranes that could be utilized in a back to-front "3 + 1" methodology to form azuliporphyrins and related heteroporphyrinoids. In addition, the favorability of azulenes toward 1,3 substitution was applied to one-pot syntheses of tetraarylazuliporphyrins and calix[4]azulenes. Azuliporphyrins have significant diatropic character that is greatly enhanced upon protonation. They have been shown to form organometallic complexes with Ni(II), Pd(II), Pt(II), Ir(III), Rh(III), and Ru(II) and undergo selective oxidations at the internal carbon with copper(II) or silver(I) salts to afford 21-oxyazuliporphyrins. In addition, oxidative ring contractions readily occur under basic conditions in the presence of peroxides to give benzocarbaporphyrins, and this reactivity provides access to tetraarylbenzocarbaporphyrins and their organometallic derivatives. A diazulenylmethane dialdehyde has been shown to react with dipyrrylmethanes in the presence of HCl or HBr to give diazuliporphyrins that were isolated in a monoprotonated form, and metalation with palladium(II) acetate afforded a stable zwitterionic palladium(II) complex. Equally intriguing dicarbaporphyrinoids incorporating indene and azulene rings have been reported, and these systems exhibit significant aromatic character. Recent studies have demonstrated that calixazulenes form supramolecular complexes with quaternary ammonium salts and afford a 1:1 complex with C60. In addition, conjugated structures have been prepared from calixazulenes that are structurally related to quatyrin, the theoretically important hydrocarbon analogue of the porphyrins. Examples of expanded azuliporphyrinoids have also been described. These azulene-containing porphyrinoids exhibit unique and complex reactivity that compares favorably with better studied porphyrin analogue systems such as the N-confused porphyrins, and azuliporphyrin derivatives show promise in the development of new catalytic systems. PMID- 26853354 TI - Polyethylene glycol hydrogel rectal spacer implantation in patients with prostate cancer undergoing combination high-dose-rate brachytherapy and external beam radiotherapy. AB - PURPOSE: To present rectal toxicity rates in patients administered a polyethylene glycol (PEG) hydrogel rectal spacer in conjunction with combination high-dose rate brachytherapy and external beam radiotherapy. METHODS AND MATERIALS: Between February 2010 and April 2015, 326 prostate carcinoma patients underwent combination high-dose-rate brachytherapy of 16 Gy (average dose 15.5 Gy; standard deviation [SD] = 1.6 Gy) and external beam radiotherapy of 59.4 Gy (average dose 60.2 Gy; SD = 2.9 Gy). In conjunction with the radiation therapy regimen, each patient was injected with 10 mL of a PEG hydrogel in the anterior perirectal fat space. The injectable spacer (rectal spacer) creates a gap between the prostate and the rectum. The rectum is displaced from the radiation field, and rectal dose is substantially reduced. The goal is a reduction in rectal radiation toxicity. Clinical efficacy was determined by measuring acute and chronic rectal toxicity using the National Cancer Center Institute Common Terminology Criteria for Adverse Events v4.0 grading scheme. RESULTS: Median followup was 16 months. The mean anterior-posterior separation achieved was 1.6 cm (SD = 0.4 cm). Rates of acute Grade 1 and 2 rectal toxicity were 37.4% and 2.8%, respectively. There were no acute Grade 3/4 toxicities. Rates of late Grade 1, 2, and 3 rectal toxicity were 12.7%, 1.4%, and 0.7%, respectively. There were no late Grade 4 toxicities. CONCLUSIONS: PEG rectal spacer implantation is safe and well tolerated. Acute and chronic rectal toxicities are low despite aggressive dose escalation. PMID- 26853360 TI - Target Selection Signals Influence Perceptual Decisions by Modulating the Onset and Rate of Evidence Accumulation. AB - Computational and neurophysiological research has highlighted neural processes that accumulate sensory evidence for perceptual decisions. These processes have been studied in the context of highly simplified perceptual discrimination paradigms in which the physical evidence appears at times and locations that are either entirely predictable or exogenously cued (e.g., by the onset of the stimulus itself). Yet, we are rarely afforded such certainty in everyday life. For example, when driving along a busy motorway, we must continually monitor the movements of surrounding vehicles for events that call for a lane change. In such scenarios, it is unknown which of the continuously present information sources will become relevant or when. Although it is well established that evidence integration provides an effective mechanism for countering the impact of noise, the question of how this mechanism is implemented in the face of uncertain evidence onsets has yet to be answered. Here, we show that when monitoring two potential sources of information for evidence occurring unpredictably in both time and space, the human brain employs discrete, early target selection signals that significantly modulate the onset and rate of neural evidence accumulation, and thereby the timing and accuracy of perceptual reports. These selection signals share many of the key characteristics of the N2pc component highlighted in the literature on visual search yet are present even in the absence of distractors and under situations of low temporal and spatial uncertainty. These data provide novel insights into how target selection supports decision making in uncertain environments. PMID- 26853359 TI - Interface Contractility between Differently Fated Cells Drives Cell Elimination and Cyst Formation. AB - Although cellular tumor-suppression mechanisms are widely studied, little is known about mechanisms that act at the level of tissues to suppress the occurrence of aberrant cells in epithelia. We find that ectopic expression of transcription factors that specify cell fates causes abnormal epithelial cysts in Drosophila imaginal discs. Cysts do not form cell autonomously but result from the juxtaposition of two cell populations with divergent fates. Juxtaposition of wild-type and aberrantly specified cells induces enrichment of actomyosin at their entire shared interface, both at adherens junctions as well as along basolateral interfaces. Experimental validation of 3D vertex model simulations demonstrates that enhanced interface contractility is sufficient to explain many morphogenetic behaviors, which depend on cell cluster size. These range from cyst formation by intermediate-sized clusters to segregation of large cell populations by formation of smooth boundaries or apical constriction in small groups of cells. In addition, we find that single cells experiencing lateral interface contractility are eliminated from tissues by apoptosis. Cysts, which disrupt epithelial continuity, form when elimination of single, aberrantly specified cells fails and cells proliferate to intermediate cell cluster sizes. Thus, increased interface contractility functions as error correction mechanism eliminating single aberrant cells from tissues, but failure leads to the formation of large, potentially disease-promoting cysts. Our results provide a novel perspective on morphogenetic mechanisms, which arise from cell-fate heterogeneities within tissues and maintain or disrupt epithelial homeostasis. PMID- 26853361 TI - A Sawtooth Pattern of Cadherin 2 Stability Mechanically Regulates Somite Morphogenesis. AB - Differential cadherin (Cdh) expression is a classical mechanism for in vitro cell sorting. Studies have explored the roles of differential Cdh levels in cell aggregates and during vertebrate gastrulation, but the role of differential Cdh activity in forming in vivo tissue boundaries and boundary extracellular matrix (ECM) is unclear. Here, we examine the interactions between cell-cell and cell ECM adhesion during somitogenesis, the formation of the segmented embryonic precursors of the vertebral column and musculature. We identify a sawtooth pattern of stable Cdh2 adhesions in which there is a posterior-to-anterior gradient of stable Cdh2 within each somite, while there is a step-like drop in stable Cdh2 along the somite boundary. Moreover, we find that the posterior somite boundary cells with high levels of stable Cdh2 have the most columnar morphology. Cdh2 is required for maximal cell aspect ratio and thus full epithelialization of the posterior somite. Loss-of-function analysis also indicates that Cdh2 acts with the fibronectin (FN) receptor integrin alpha5 (Itgalpha5) to promote somite boundary formation. Using genetic mosaics, we demonstrate that differential Cdh2 levels are sufficient to induce boundary formation, Itgalpha5 activation, and FN matrix assembly in the paraxial mesoderm. Elevated cytoskeletal contractility is sufficient to replace differential Cdh2 levels in genetic mosaics, suggesting that Cdh2 promotes ECM assembly by increasing cytoskeletal and tissue stiffness along the posterior somite boundary. Throughout somitogenesis, Cdh2 promotes ECM assembly along tissue boundaries and inhibits ECM assembly in the tissue mesenchyme. PMID- 26853363 TI - Priming Spatial Activity by Single-Cell Stimulation in the Dentate Gyrus of Freely Moving Rats. AB - An essential requirement for hippocampal circuits to function in episodic memory is the ability to rapidly disambiguate and store incoming sensory information. This "pattern separation" function has been classically associated to the dentate gyrus, where spatial learning is accompanied by rapid and persistent modifications of place-cell representation. How these rapid modifications are implemented at the cellular level has remained largely unresolved. Here, we tested whether plasticity-inducing stimuli--spike trains--evoked in postsynaptic neurons are sufficient for the rapid induction of place-field activity in the dentate gyrus. We juxtacellularly stimulated 67 silent granule cells while rats explored a maze for the first time. Spike trains with different characteristics (e.g., number of spikes, frequency, and theta-rhythmicity) were evoked at randomly selected spatial locations. We found that, under novelty, ~30% (10/33) of the stimulated neurons fired selectively at the "primed" spatial location on subsequent laps. Induced place fields were either transient or persisted for multiple laps. The "priming" effect was experience dependent, as it was less frequently observed in habituated animals (3/34 neurons), and it correlated with the number of spikes and theta-rhythmicity of the stimulus trains. These data indicate that, albeit with low efficiency, evoked theta-rhythmic spike trains can be sufficient for priming spatial activity in the dentate gyrus and thus recruiting silent granule cells into the coding population. PMID- 26853362 TI - Pleistocene Mitochondrial Genomes Suggest a Single Major Dispersal of Non Africans and a Late Glacial Population Turnover in Europe. AB - How modern humans dispersed into Eurasia and Australasia, including the number of separate expansions and their timings, is highly debated [1, 2]. Two categories of models are proposed for the dispersal of non-Africans: (1) single dispersal, i.e., a single major diffusion of modern humans across Eurasia and Australasia [3 5]; and (2) multiple dispersal, i.e., additional earlier population expansions that may have contributed to the genetic diversity of some present-day humans outside of Africa [6-9]. Many variants of these models focus largely on Asia and Australasia, neglecting human dispersal into Europe, thus explaining only a subset of the entire colonization process outside of Africa [3-5, 8, 9]. The genetic diversity of the first modern humans who spread into Europe during the Late Pleistocene and the impact of subsequent climatic events on their demography are largely unknown. Here we analyze 55 complete human mitochondrial genomes (mtDNAs) of hunter-gatherers spanning ~35,000 years of European prehistory. We unexpectedly find mtDNA lineage M in individuals prior to the Last Glacial Maximum (LGM). This lineage is absent in contemporary Europeans, although it is found at high frequency in modern Asians, Australasians, and Native Americans. Dating the most recent common ancestor of each of the modern non-African mtDNA clades reveals their single, late, and rapid dispersal less than 55,000 years ago. Demographic modeling not only indicates an LGM genetic bottleneck, but also provides surprising evidence of a major population turnover in Europe around 14,500 years ago during the Late Glacial, a period of climatic instability at the end of the Pleistocene. PMID- 26853364 TI - Sensitivity to Relational Similarity and Object Similarity in Apes and Children. AB - Relational reasoning is a hallmark of sophisticated cognition in humans. Does it exist in other primates? Despite some affirmative answers, there appears to be a wide gap in relational ability between humans and other primates--even other apes. Here, we test one possible explanation for this gap, motivated by developmental research showing that young humans often fail at relational reasoning tasks because they focus on objects instead of relations. When asked, "duck:duckling is like tiger:?," preschool children choose another duckling (object match) rather than a cub. If other apes share this focus on concrete objects, it could undermine their relational reasoning in similar ways. To test this, we compared great apes and 3-year-old humans' relational reasoning on the same spatial mapping task, with and without competing object matches. Without competing object matches, both children and Pan species (chimpanzees and bonobos) spontaneously used relational similarity, albeit children more so. But when object matches were present, only children responded strongly to them. We conclude that the relational gap is not due to great apes' preference for concrete objects. In fact, young humans show greater object focus than nonhuman apes. PMID- 26853365 TI - Unexpected Convergent Evolution of Nasal Domes between Pleistocene Bovids and Cretaceous Hadrosaur Dinosaurs. AB - The fossil record provides tangible, historical evidence for the mode and operation of evolution across deep time. Striking patterns of convergence are some of the strongest examples of these operations, whereby, over time, similar environmental and/or behavioral pressures precipitate similarity in form and function between disparately related taxa. Here we present fossil evidence for an unexpected convergence between gregarious plant-eating mammals and dinosaurs. Recent excavations of Late Pleistocene deposits on Rusinga Island, Kenya, have uncovered a catastrophic assemblage of the wildebeest-like bovid Rusingoryx atopocranion. Previously known from fragmentary material, these new specimens reveal large, hollow, osseous nasal crests: a craniofacial novelty for mammals that is remarkably comparable to the nasal crests of lambeosaurine hadrosaur dinosaurs. Using adult and juvenile material from this assemblage, as well as computed tomographic imaging, we investigate this convergence from morphological, developmental, functional, and paleoenvironmental perspectives. Our detailed analyses reveal broad parallels between R. atopocranion and basal Lambeosaurinae, suggesting that osseous nasal crests may require a highly specific combination of ontogeny, evolution, and environmental pressures in order to develop. PMID- 26853367 TI - Cell Competition Drives the Formation of Metastatic Tumors in a Drosophila Model of Epithelial Tumor Formation. AB - Cell competition is a homeostatic process in which proliferating cells compete for survival. Elimination of otherwise normal healthy cells through competition is important during development and has recently been shown to contribute to maintaining tissue health during organismal aging. The mechanisms that allow for ongoing cell competition during adult life could, in principle, contribute to tumorigenesis. However, direct evidence supporting this hypothesis has been lacking. Here, we provide evidence that cell competition drives tumor formation in a Drosophila model of epithelial cancer. Cells expressing EGFR together with the conserved microRNA miR-8 acquire the properties of supercompetitors. Neoplastic transformation and metastasis depend on the ability of these cells to induce apoptosis and engulf nearby cells. miR-8 expression causes genome instability by downregulating expression of the Septin family protein Peanut. Cytokinesis failure due to downregulation of Peanut is required for tumorigenesis. This study provides evidence that the cellular mechanisms that drive cell competition during normal tissue growth can be co-opted to drive tumor formation and metastasis. Analogous mechanisms for cytokinesis failure may lead to polyploid intermediates in tumorigenesis in mammalian cancer models. PMID- 26853366 TI - Cell Competition Drives the Growth of Intestinal Adenomas in Drosophila. AB - Tumor-host interactions play an increasingly recognized role in modulating tumor growth. Thus, understanding the nature and impact of this complex bidirectional communication is key to identifying successful anti-cancer strategies. It has been proposed that tumor cells compete with and kill neighboring host tissue to clear space that they can expand into; however, this has not been demonstrated experimentally. Here we use the adult fly intestine to investigate the existence and characterize the role of competitive tumor-host interactions. We show that APC(-/-)-driven intestinal adenomas compete with and kill surrounding cells, causing host tissue attrition. Importantly, we demonstrate that preventing cell competition, by expressing apoptosis inhibitors, restores host tissue growth and contains adenoma expansion, indicating that cell competition is essential for tumor growth. We further show that JNK signaling is activated inside the tumor and in nearby tissue and is required for both tumor growth and cell competition. Lastly, we find that APC(-/-) cells display higher Yorkie (YAP) activity than host cells and that this promotes tumor growth, in part via cell competition. Crucially, we find that relative, rather than absolute, Hippo activity determines adenoma growth. Overall, our data indicate that the intrinsic over-proliferative capacity of APC(-/-) cells is not uncontrolled and can be constrained by host tissues if cell competition is inhibited, suggesting novel possible therapeutic approaches. PMID- 26853368 TI - Distinct Computational Principles Govern Multisensory Integration in Primary Sensory and Association Cortices. AB - Human observers typically integrate sensory signals in a statistically optimal fashion into a coherent percept by weighting them in proportion to their reliabilities. An emerging debate in neuroscience is to which extent multisensory integration emerges already in primary sensory areas or is deferred to higher order association areas. This fMRI study used multivariate pattern decoding to characterize the computational principles that define how auditory and visual signals are integrated into spatial representations across the cortical hierarchy. Our results reveal small multisensory influences that were limited to a spatial window of integration in primary sensory areas. By contrast, parietal cortices integrated signals weighted by their sensory reliabilities and task relevance in line with behavioral performance and principles of statistical optimality. Intriguingly, audiovisual integration in parietal cortices was attenuated for large spatial disparities when signals were unlikely to originate from a common source. Our results demonstrate that multisensory interactions in primary and association cortices are governed by distinct computational principles. In primary visual cortices, spatial disparity controlled the influence of non-visual signals on the formation of spatial representations, whereas in parietal cortices, it determined the influence of task-irrelevant signals. Critically, only parietal cortices integrated signals weighted by their bottom-up reliabilities and top-down task relevance into multisensory spatial priority maps to guide spatial orienting. PMID- 26853369 TI - Hand hygiene-related clinical trials reported since 2010: a systematic review. AB - Considerable emphasis is currently placed on reducing healthcare-associated infection through improving hand hygiene compliance among healthcare professionals. There is also increasing discussion in the lay media of perceived poor hand hygiene compliance among healthcare staff. Our aim was to report the outcomes of a systematic search for peer-reviewed, published studies - especially clinical trials - that focused on hand hygiene compliance among healthcare professionals. Literature published between December 2009, after publication of the World Health Organization (WHO) hand hygiene guidelines, and February 2014, which was indexed in PubMed and CINAHL on the topic of hand hygiene compliance, was searched. Following examination of relevance and methodology of the 57 publications initially retrieved, 16 clinical trials were finally included in the review. The majority of studies were conducted in the USA and Europe. The intensive care unit emerged as the predominant focus of studies followed by facilities for care of the elderly. The category of healthcare worker most often the focus of the research was the nurse, followed by the healthcare assistant and the doctor. The unit of analysis reported for hand hygiene compliance was 'hand hygiene opportunity'; four studies adopted the 'my five moments for hand hygiene' framework, as set out in the WHO guidelines, whereas other papers focused on unique multimodal strategies of varying design. We concluded that adopting a multimodal approach to hand hygiene improvement intervention strategies, whether guided by the WHO framework or by another tested multimodal framework, results in moderate improvements in hand hygiene compliance. PMID- 26853370 TI - Gold nanoparticles as sensitive optical probes. AB - Gold nanoparticles (Au NPs) have become one of the most popular materials for sensing of analytes of interest in the last decade, mainly because of their ease in preparation and conjugation, stability, biocompatibility, and size-dependent optical properties. We have witnessed many sensitive and selective Au NP based optical systems for the quantitation of metal ions, anions, proteins, and DNA, based on analyte induced changes in their absorption, fluorescence, and scattering. In this tutorial review, we briefly discuss wet chemical approaches for the preparation of Au NPs. Sensing mechanisms and strategies of Au NP based optical systems are provided to show basic concepts in designing sensitive and selective sensing systems. Strategies for signal amplification applied in Au NP based systems are emphasized for the analysis of trace amounts of analytes in real samples. Many excellent Au NP based optical sensing systems are discussed to highlight their practicality for the analysis of complicated biological and environmental samples. The tutorial review ends with the discussion of the challenges and future trends of Au NP based optical sensing systems. PMID- 26853371 TI - Soft tissue cephalometric norms of Iranian Class I adults with good occlusions and balanced faces. AB - AIM: The aim of this study was to assess the soft tissue measurements of Iranians with good occlusion and to compare the Iranian norms with other ethnicities. MATERIALS AND METHODS: A total of 25 anthropometric variables were measured by a dentist in 50 Iranian Class I subjects (25 males, 25 females) with good occlusion and well-balanced faces. The differences between the two genders, as well as the differences between Iranian norms and the Holdaway and Burstone analyses, were statistically analyzed using a t-test (alpha=0.05). RESULTS: The subjects' mean age was 21.6+/-4.1 years. There were significant differences between males and females regarding the mentocervical angle, the nasolabial angle, Merrifield's Z angle, the angle of facial convexity, soft tissue chin thickness, and upper lip thickness (P<0.05). The Holdaway norms can be used for the Iranian population, except for the following measurements which might be significantly different: facial convexity angle, nasolabial angle, interlabial gap, soft tissue facial angle, skeletal profile convexity, H-angle, lower lip to H-line, lower sulcus depth, and soft tissue chin thickness (P<0.05). CONCLUSIONS: There was a considerable sex dimorphism in the Iranian population. The Holdaway norms are not useful for the Iranian population regarding most measurements. PMID- 26853373 TI - I2 mediated synthesis of 5-substituted-3-methyl/benzyl-1,3,4-oxadiazol-2(3H)-ones via sequential condensation/oxidative cyclization and rearrangement. AB - A simple and efficient iodine-assisted protocol for the synthesis of 5 substituted-3-methyl/benzyl-1,3,4-oxadiazol-2(3H)-ones has been developed. The reaction involves a sequential condensation followed by tandem oxidative cyclization and rearrangement of readily available methyl/benzyl carbazates and aldehydes as starting substrates. The presence of iodine and base promotes intramolecular C-O bond formation, followed by Chapman-like rearrangement at 90 degrees C of the methyl/benzyl group in the hydrazone intermediate formed during the condensation step. This transition-metal-free approach has been adopted to generate a variety of oxadiazolones under mild conditions in good to excellent yields. PMID- 26853374 TI - The relationships among personality, social support, and resilience of abused nurses at emergency rooms and psychiatric wards in Taiwan. AB - The aim of the authors in this study was to identify factors associated with resilience that helped abused nurses face and cope with violent events. The data for this cross-sectional study were collected from June 2013 to December 2013; 272 participants were recruited from emergency rooms and psychiatric wards in four hospitals in central Taiwan. Among these participants, 230 (84.6%) met the inclusion criterion and completed all questionnaires; 69 (30%) of them reported having experienced only verbal violence; 46 (20%) reported having experienced only physical violence, and 115 (50%) reported having experienced a combination of verbal and physical violence. The following were positively associated with resilience score: having a college education or greater (exp(beta) = 1.045, p = .018), extraversion (exp(beta) = 1.012 per unit increase in the score, p < .001), family support (exp(beta) = 1.004 per unit increase in the score, p = .031), peer support (exp(beta) = 1.008 per unit increase in the score, p = .006), and lower level of neuroticism (exp(beta) = 0.983 per unit increase in the score, p < .001); 43.6% of the variance in resilience was explained by the variables assessed. Adequate support and advanced education are important for abused nurses to enhance their resilience. PMID- 26853375 TI - Boston Society's 11th Annual Applied Pharmaceutical Analysis conference. AB - Boston Society's 11th Annual Applied Pharmaceutical Analysis conference, Hyatt Regency Hotel, Cambridge, MA, USA, 14-16 September 2015 The Boston Society's 11th Annual Applied Pharmaceutical Analysis (APA) conference took place at the Hyatt Regency hotel in Cambridge, MA, on 14-16 September 2015. The 3-day conference affords pharmaceutical professionals, academic researchers and industry regulators the opportunity to collectively participate in meaningful and relevant discussions impacting the areas of pharmaceutical drug development. The APA conference was organized in three workshops encompassing the disciplines of regulated bioanalysis, discovery bioanalysis (encompassing new and emerging technologies) and biotransformation. The conference included a short course titled 'Bioanalytical considerations for the clinical development of antibody drug conjugates (ADCs)', an engaging poster session, several panel and round table discussions and over 50 diverse talks from leading industry and academic scientists. PMID- 26853376 TI - P3HT:DiPBI bulk heterojunction solar cells: morphology and electronic structure probed by multiscale simulation and UV/vis spectroscopy. AB - Coarse grained molecular dynamics simulations are performed for a mixture of poly(3-hexylthiophene) (P3HT) and diperylene bisimide (DiPBI). The effect of different annealing and cooling protocols on the morphology is investigated and the resulting domain structures are analyzed. In particular, pi-stacked clusters of DiPBI molecules are observed whose size decreases with increasing temperature. Domain structure and diffusivity data suggest that the DiPBI subsystem undergoes an order -> disorder phase transition between 700 and 900 K. Electronic structure calculations based on density functional theory are carried out after backmapping the coarse grained model onto an atomistic force field representation built upon first principles. UV/vis absorption spectra of the P3HT:DiPBI mixture are computed using time-dependent density functional linear response theory and recorded experimentally for a spin-coated thin film. It is demonstrated that the absorption spectrum depends sensitively on the details of the amorphous structure, thus providing valuable insight into the morphology. In particular, the results show that the tempering procedure has a significant influence on the material's electronic properties. This knowledge may help to develop effective processing routines to enhance the performance of bulk heterojunction solar cells. PMID- 26853377 TI - Long-term outcomes after moderate-to-severe traumatic brain injury among military veterans: Successes and challenges. AB - OBJECTIVE: To assess long-term outcomes after traumatic brain injury (TBI) among veterans and service members. SETTING: Regional Veterans Affairs medical centre. PARTICIPANTS: One hundred and eighteen veterans and military personnel, aged 23 70 years (median = 35 years), 90% male, had moderate-to-severe TBI (82% in coma > 1 day, 85% amnesic > 7 days), followed by acute interdisciplinary rehabilitation 5-16 years ago (median = 8 years). DESIGN: Cross-sectional analysis of live interviews conducted via telephone. MAIN MEASURES: TBI follow-up interview (occupational, social, cognitive, neurologic and psychiatric ratings), Community Integration Questionnaire, Disability Rating Scale (four indices of independent function) and Satisfaction with Life Scale. RESULTS: At follow-up, 52% of participants were working or attending school; 34% ended or began marriages after TBI, but the overall proportion married changed little. Finally, 22% were still moderately-to-severely disabled. However, 62% of participants judged themselves to be as satisfied or more satisfied with life than before injury. Injury severity, especially post-traumatic amnesia, was correlated with poorer outcomes in all functional domains. CONCLUSIONS: After moderate-severe TBI, most veterans assume productive roles and are satisfied with life. However, widespread difficulties and functional limitations persist. These findings suggest that veteran and military healthcare systems should continue periodic, comprehensive follow-up evaluations long after moderate-to-severe TBI. PMID- 26853379 TI - A Bismuth-Halide Double Perovskite with Long Carrier Recombination Lifetime for Photovoltaic Applications. AB - Despite the remarkable rise in efficiencies of solar cells containing the lead halide perovskite absorbers RPbX3 (R = organic cation; X = Br(-) or I(-)), the toxicity of lead remains a concern for the large-scale implementation of this technology. This has spurred the search for lead-free materials with similar optoelectronic properties. Here, we use the double-perovskite structure to incorporate nontoxic Bi(3+) into the perovskite lattice in Cs2AgBiBr6 (1). The solid shows a long room-temperature fundamental photoluminescence (PL) lifetime of ca. 660 ns, which is very encouraging for photovoltaic applications. Comparison between single-crystal and powder PL decay curves of 1 suggests inherently high defect tolerance. The material has an indirect bandgap of 1.95 eV, suited for a tandem solar cell. Furthermore, 1 is significantly more heat and moisture stable compared to (MA)PbI3. The extremely promising optical and physical properties of 1 shown here motivate further exploration of both inorganic and hybrid halide double perovskites for photovoltaics and other optoelectronics. PMID- 26853378 TI - Liquid-liquid extraction of antimicrobial peptide P34 by aqueous two-phase and micellar systems. AB - Antimicrobial peptide P34 is a promising biopreservative for utilization in the food industry. In this work, aqueous biphasic systems (ABS) and aqueous biphasic micellar systems (ABMS) were studied as prestep for purification of peptide P34. The ABS was prepared with polyethylene glycol (PEG) and inorganic salts and the ABMS with Triton X-114 was chosen as the phase-forming surfactant. Results indicate that peptide P34 partitions preferentially to PEG-rich phase and extraction with ammonium sulfate [(NH4)2SO4], yielding a 75% recovery of the antimicrobial activity, specific activity of 1,530 antimicrobial units per mg of protein, and purification fold of 2.48. Protein partition coefficient and partition coefficient for the biological activity with (NH4)2SO4 system were 0.48 and 64, respectively. Addition of sodium chloride did not affect recovery, but decreased protein amount in the PEG-rich phase, indicating a higher partition of biomolecules. ABMS did not yield good recovery of antimicrobial activity. Purification fold using PEG-(NH4)2SO4 and 1.0 mol l-1 sodium chloride was twice higher than that obtained by conventional protocol, indicating a successful utilization of ABS as a step for purification of peptide P34. PMID- 26853380 TI - Recent highlights in mixed-coordinate oligophosphorus chemistry. AB - This review aims to highlight and comprehensively summarize recent developments in the field of mixed-coordinate phosphorus chemistry. Particular attention is focused on the synthetic approaches to compounds containing at least two directly bonded phosphorus atoms in different coordination environments and their unexpected properties that are derived from spectroscopic and crystallographic data. Novel substance classes are discussed in order to supplement previous reviews about mixed-coordinate phosphorus compounds. PMID- 26853381 TI - Novel strategies for the synthesis of unsymmetrical glycosyl disulfides. AB - Novel strategies for the efficient synthesis of unsymmetrical glycosyl disulfides are reported. Glycosyl disulfides are increasingly important as glycomimetics and molecular probes in glycobiology. Sialosyl disulfides are synthesised directly from the chlorosialoside Neu5Ac2Cl, proceeding via a thiol-disulfide exchange reaction between the sialosyl thiolate and symmetrical disulfides. This methodology was adapted and found to be successfully applicable to the synthesis of unsymmetrical glucosyl disulfides under mild conditions. PMID- 26853382 TI - Probing the PEDOT:PSS/cell interface with conductive colloidal probe AFM-SECM. AB - Conductive colloidal probe Atomic Force-Scanning Electrochemical Microscopy (AFM SECM) is a new approach, which employs electrically insulated AFM probes except for a gold-coated colloid located at the end of the cantilever. Hence, force measurements can be performed while biasing the conductive colloid under physiological conditions. Moreover, such colloids can be modified by electrochemical polymerization resulting, e.g. in conductive polymer-coated spheres, which in addition may be loaded with specific dopants. In contrast to other AFM-based single cell force spectroscopy measurements, these probes allow adhesion measurements at the cell-biomaterial interface on multiple cells in a rapid manner while the properties of the polymer can be changed by applying a bias. In addition, spatially resolved electrochemical information e.g., oxygen reduction can be obtained simultaneously. Conductive colloid AFM-SECM probes modified with poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate ( PEDOT: PSS) are used for single cell force measurements in mouse fibroblasts and single cell interactions are investigated as a function of the applied potential. PMID- 26853383 TI - Immune responses of a wall lizard to whole-body exposure to radiofrequency electromagnetic radiation. AB - PURPOSE: During the last three decades, the number of devices that emit non ionizing electromagnetic radiation (EMR) at the wireless communication spectrum has rapidly increased and possible effects on living organisms have become a major concern. The purpose of this study was to investigate the effects of radiofrequency EMR emitted by a widely used wireless communication device, namely the Digital Enhanced Communication Telephony (DECT) base, on the immune responses of the Aegean wall lizard (Podarcis erhardii). MATERIALS AND METHODS: Adult male lizards were exposed 24 h/day for 8 weeks to 1880-1900 MHz DECT base radiation at average electric field intensity of 3.2 V/m. Immune reactivity was assessed using the phytohemagglutinin (PHA) skin swelling and mixed lymphocyte reaction (MLR) tests. RESULTS: Our results revealed a noticeable suppression (approximately 45%) of inflammatory responses in EMR-exposed lizards compared to sham-exposed animals. T cell-mediated responses were marginally affected. CONCLUSION: Daily radiofrequency EMR exposure seems to affect, at least partially, the immunocompetence of the Aegean wall lizard. PMID- 26853384 TI - Development of an instrument for measuring activities of daily living in persons with suspected cognitive impairment. AB - BACKGROUND: According to the Swedish National Board of Health and Welfare, structured assessment of function and activity has high priority when evaluating suspected cognitive impairment or dementia. AIM/OBJECTIVES: The aim was to develop and psychometrically test an instrument to measure the ability to perform activities of daily living tasks in patients with suspected cognitive impairment. MATERIAL AND METHODS: The Cognitive Impairment in Daily Life (CID) instrument (for self-reported and informant-based assessments) has been developed in several phases. Content validity was achieved through five expert panels using a Content Validity Index (CVI). The content was tested further in a pilot study of 49 patients and 49 relatives from primary care or a specialist memory clinic. RESULTS: Content validity was good with a CVI index of 0.83. All patients considered that the included activities were relevant to them and reflected the difficulties they were experiencing. Most relatives considered the activities included in the instrument as adequate and captured the patients' difficulties in daily life. Some adjustments of the tasks and scale were suggested and these were implicated after each phase. In general, relatives reported that patients had more difficulties performing the activities than the patients reported themselves. CONCLUSION: The CID instrument seems promising in terms of content validity. Further testing of reliability and construct validity is ongoing. PMID- 26853385 TI - The discovery of a novel antagonist - Manduca sexta allatotropin analogue - as an insect midgut active ion transport inhibitor. AB - BACKGROUND: The midgut is an important site for both nutrient absorption and ionic regulation in lepidopteran larvae, major pests in agriculture. The larval lepidopteran midgut has become a potent insecticide target over the past few decades. Recent studies have shown that an insect neuropeptide, Manduca sexta allatotropin (Manse-AT), exhibits inhibition of active ion transport (AIT) across the larval midgut epithelium. The full characteristic of the AIT inhibition capacity of Manse-AT is essential to assay. In this study, AIT inhibition across the M. sexta midgut by Manse-AT and its analogues in a range of concentrations was assayed. The structure-activity relationship of Manse-AT was also studied by truncated and alanine-replacement strategies. RESULTS: Our results identified three residues, Thr4, Arg6 and Phe8, as the most important components for activity on the midgut. Replacement of Glu1, Met2 and Met3 reduced the potency of the analogues. The conservative substitution of Gly7 with alanine had little effect on the potency of the analogues. We demonstrated for the first time that Manse-AT (10-13) behaves as a potent antagonist in vitro on active ion transport across the epithelium of the posterior midgut in M. sexta. CONCLUSION: Structure activity studies of Manse-AT are useful in developing lead compounds for the design and testing of synthetic antagonists, ultimately to develop potent and specific pest control strategies. Manse-AT (10-13) has been discovered as the first Manse-AT antagonist, with a significant effect and a short sequence compared with other insect neuropeptides. It may be a new potential pest control agent in the future. (c) 2016 Society of Chemical Industry. PMID- 26853386 TI - International nutrition capacity building--A global SIOP-PODC model from India. PMID- 26853387 TI - Synovial sarcoma of the omentum: A rare entity. PMID- 26853388 TI - Metastasis to bilateral breasts from maxillary embryonal rhabdomyosarcoma demonstrated on F-18 FDG PET/CECT. PMID- 26853389 TI - Approach to metabolic syndrome in childhood cancer survivors. AB - The combined effects of optimized chemotherapy, surgery, radiotherapy, stem cell transplantation regimens, and improved supportive care had drastically increased the survival rate of childhood cancer. Hence, the number of adult survivors of childhood cancer is on the raise and this subset of population is gaining more attention due to the late effects of their cancer therapy. There is growing evidence that pediatric cancer survivors are at a greater risk of developing metabolic syndrome (MS) or the MS component traits than the general population. There is currently no drug therapy to treat MS as a whole disease, as it is a cluster of symptoms that present uniquely among different individuals. Given the recent recognition of MS in adult survivors of childhood cancer, there is a scarcity of long-term follow-up studies of this group. Adherence to a healthy lifestyle with both dietary and physical activity is the only most powerful and most useful armor available now against obesity and its metabolic complications. PMID- 26853390 TI - Nutritional status in children with cancer: Before, during and after therapy. AB - CONTEXT: Malnutrition is prevalent in children with cancer at diagnosis, especially in low- and middle-income countries (LMIC) where the great majority of children live. It is associated with an added burden of morbidity and mortality. AIMS: Answers were sought to the best measure of nutritional status in LMIC, the impact of anti-neoplastic therapy, effective interventions to achieve normal nutritional status and the impact of these on clinical outcomes. RESULTS: Arm anthropometry offers reasonable estimates of fat mass and lean body mass that are both impacted adversely by treatment. Nutritional supplementation, including the use of simple local resources, is beneficial and can improve survival. Long-term survivors may continue to exhibit perturbed nutritional status. CONCLUSIONS: The prevalence and severity of malnutrition in children with cancer in LMIC demand attention. Opportunities exist to conduct studies in India to examine the effects of nutritional interventions, including on the overall well-being of survivors. PMID- 26853391 TI - Importance of nutrition in pediatric oncology. AB - A nutritional perspective within pediatric oncology is usually just related to the supportive care aspect during the management of the underlying malignancy. However, nutrition has a far more fundamental importance with respect to a growing, developing child who has cancer as well as viewing cancer from a nutritional cancer control perspective. Nutrition is relevant to all components of cancer control including prevention, epidemiology, biology, treatment, supportive care, rehabilitation, and survivorship. This article briefly describes this perspective of nutrition within a cancer control context and is a summary of the presentation at the "1st International SIOP-PODC Workshop on Nutrition in Children with Cancer" held in Mumbai. PMID- 26853392 TI - Non-Hodgkin's lymphoma of the infratemporal fossa: A case report. PMID- 26853393 TI - Ileocaecal Metastasis from Carcinoma Cervix presenting with bowel obstruction: A rare case report. PMID- 26853394 TI - Trends of reported cases of retinoblastoma post-enucleation seeking prosthetic rehabilitation: Few annotations. PMID- 26853395 TI - Parenteral and enteral nutrition for pediatric oncology in low- and middle-income countries. AB - Although nutritional therapy is essential for the treatment of childhood cancer, it remains a challenge, especially within the developing world, where there are many barriers to optimizing treatment. The oral route is the first approach to nutritional support, however challenging this might be in children with cancer. Oral supplements are indicated in moderate evaluated nutritional risk patients and its use should consider the family's social conditions and access to industrialized oral supplements. If unavailable, homemade oral supplements can be used respecting regional accessibility, local foods, and culture. Nonetheless, many patients cannot sustain nutritional status on oral feeding alone and need to be supported by enteral tube feeding. Enteral feeding may be modified to accommodate the financial constraints of institution in low- and middle-income countries (LMICs). In some oncologic situations, however, enteral nutrition is not possible and parenteral nutrition is indicated, although only if the need for nutritional support is anticipated to be longer than 5-7 days. Nutritional support in pediatric oncology remains a challenge, especially in LMICs, however, it can be undertaken by getting the best out of the available resources. PMID- 26853396 TI - OrthOncoCon-2014: Continuing education in musculoskeletal oncology. PMID- 26853397 TI - Nutritional assessment and intervention in a pediatric oncology unit. AB - Nutritional status in children with cancer is an important prognostic factor. Assessment consisting of anthropometry, biochemistry, clinical, and diet that needs to be done on diagnosis and regularly to ensure that patient's nutritional status does not deteriorate. In developing countries, assessment will depend on the availability of all resources, but monitoring is essential. The development of malnutrition during treatment is possible and the reasons are multifactorial. Nutrition plays a deciding role and a key factor in children with cancer and can influence their outcome. PMID- 26853398 TI - Triple negative epithelial ovarian cancer: "A new entity". PMID- 26853399 TI - A survey of nutritional practices for children with cancer in India. AB - BACKGROUND: Assessing nutritional status and delivering optimal nutritional care is a part of modern day treatment of children with cancer. The nutritional practices in India for these children have not been previously described. AIMS: To describe the existing nutrition assessment and management practices for children with cancer in India. METHODS: Attendees of the First International Society of Pediatric Oncology-Pediatric Oncology in Developing Countries workshop on nutrition in children with cancer organized in September 2014 at Tata Memorial Hospital, Mumbai, India were invited to complete a self-administered questionnaire related to three domains: nutritional assessment, intervention, and education. RESULTS: Hundred and eight respondents from 42 health institutions and background in the health sector participated in the survey. There was variability in nutritional assessment, practice and education. Lack of resources and time are contributory. CONCLUSIONS: This assessment of nutritional services in India provided useful information to plan development of national guidelines, policy, and delivery of services. PMID- 26853400 TI - T-cell chronic lymphocytic leukemia/T-prolymphocytic leukemia: Experience with single agent bendamustine. PMID- 26853401 TI - Adiponectin correlates with obesity: A study of 159 childhood acute leukemia survivors from India. AB - BACKGROUND: Acute lymphoblastic leukemia survivors are predisposed to obesity. However, the exact underlying mechanisms are not known. AIMS: The study was done to assess the role of biomarkers of obesity in acute leukemia survivors. SETTINGS AND DESIGNS: This is a cross-sectional study conducted at All India Institute of Medical Sciences in survivors of acute leukemia who had completed treatment at least 1 year before enrollment in this study. MATERIALS AND METHODS: Obesity was studied by determining the body mass index. Potential biomarkers were studied by assessing serum leptin, resistin, and adiponectin by enzyme-linked immunosorbant assay, and the results were compared in obese versus nonobese survivors. STATISTICAL ANALYSIS: Descriptive analysis for baseline demographic factors and Student's t-test for comparing the mean levels of biomarkers among the obese and nonobese survivors. RESULTS: One hundred and fifty-nine acute leukemia patients were enrolled in this study with a median follow-up of 36.8 months. The median age was 10 (range: 3-18) years, and 123 (77.3%) patients were males. The overall prevalence of overweight/obesity was 26.4%, and this was similar in acute myeloid leukemia and acute lymphoblastic leukemia sub-groups (26.2% vs. 27.3%, P = 0.9). Mean serum leptin and resistin were similar in obese and nonobese leukemia survivors (3.7 vs. 2.85 pg/mL, P = 0.064; 8.01 vs. 9.33 ng/mL, P = 0.36). However, mean serum adiponectin was significantly lower in obese leukemia survivors (7.97 vs. 11.5 MUg/mL, P = 0.023). CONCLUSIONS: Obese leukemic survivors had lower serum adiponectin levels than nonobese survivors. However, serum resistin and leptin levels were similar in the two groups. PMID- 26853402 TI - Invasion of lung cancer into breast: The first case report. PMID- 26853403 TI - Indicators of malnutrition in children with cancer: A study of 690 patients from a tertiary care cancer center. AB - BACKGROUND: Large data pertaining to indicators of malnutrition in children with cancer is lacking from India. In view of this, we prospectively analyzed consecutive de novo childhood patients with cancer presenting at a tertiary care center. MATERIALS AND METHODS: Height and weight of each child (n = 690) were compared with World Health Organization child growth standards-2006 for that particular age and sex to get weight-for-age, height-for-age, and weight-for height indices and below 2SD of the reference median on these indices were considered as underweight, stunted, and wasted, respectively. Body mass index (BMI) for age was also analyzed for thinness and obesity. RESULTS: Prevalence of malnutrition based on Z-score for weight-for-age, height-for-age, weight-for height, and BMI-for-age was 30%, 31%, 35%, and 41%, respectively. Weight-for-age (underweight) was significantly associated (P = 0.018) with solid tumors. Height for-age, weight-for-age, and BMI-for-age were significantly associated (P = 0.007, P = 0.016, and P <= 0.001, respectively) with rural community. CONCLUSION: Malnutrition was observed in approximately one-third of children with cancer. Malnutrition is associated with solid tumors and those coming from rural community. Wasting has a higher prevalence in children with cancer in <5 years of age group. PMID- 26853404 TI - Three squamous cell carcinomas of different sites in three years: A mere coincidence? PMID- 26853405 TI - The impact of weight for age on survival in acute lymphoblastic leukemia: Report from a tertiary care center in North India. AB - BACKGROUND: Undernutrition is considered to have a negative impact on survival in children with malignancies. The objective of this retrospective analysis was to evaluate the morbidity pattern and outcome of therapy in undernourished (UN) children with acute lymphoblastic leukemia. METHODS: A retrospective analysis of impact of weight for age was performed in children treated for ALL. The IAP & CDC criteria for undernutrition were used in the two different time periods of analysis. RESULTS: There were two cohorts in the study: Between 1995 and 2005, 360 children were evaluated where the weight for age was classified using the Indian Academy of Pediatrics criteria for undernourishment (Group A). Group B of the study included 373 children treated from 2007 to 2011, who were graded as per the Centers for Disease Control criteria for weight for age. In Group A, 35% of the children were malnourished at presentation. The morbidity and supportive care needed in the well-nourished and UN group were similar. The event-free survival and mortality were similar in both groups. Analysis of Group B showed an overall survival of 62.6% with a greater survival in children with a weight of >=10th centile for age compared to children at the <10th centile, (P = 0.026) with a higher mortality (P = 0.011) in the UN group. CONCLUSION: Our data have yielded conflicting results. The older cohort did not show a significant difference in survival using malnutrition as a risk factor. However, in the subsequent cohort, a difference in survival was noted. This could be due to the reason that different criteria for classification of undernutrition were applied in the two groups. This analysis lays the foundation for a future prospective analysis to evaluate nutrition as an independent risk factor nutrition as an independent risk factor in the outcome of childhood malignancies. PMID- 26853406 TI - Nutritional profile of pediatric cancer patients at Cancer Institute, Chennai. AB - BACKGROUND: Malnutrition is widely prevalent in the pediatric population in India. There is paucity of data on the prevalence of malnutrition in pediatric cancer patients and the impact of cancer treatment on nutritional status of Indian children. AIMS: The study was conducted to look at the prevalence of malnutrition and assess the impact of treatment on nutritional status of pediatric cancer patients. SETTINGS AND DESIGN: This was a retrospective study. MATERIALS AND METHODS: Data on the weight of pediatric cancer patients <16 years of age treated at Cancer Institute, Chennai, from January 2013 to May 2014 were analyzed at systematic time points in therapy. Patients' weight were plotted on the Centre for Disease Control (CDC) growth charts. Patients were defined to be undernourished if their weight for age was <=3rd centile in CDC growth charts and obese if their weight for age was >=97th centile on CDC growth charts. RESULTS: A total of 295 patient case records were analyzed. Acute lymphoblastic leukemia was the most common malignancy. At diagnosis, under-nutrition was seen in 44% patients, this increased to 46% midway during treatment (end of induction in acute leukemia and completion of 50% of planned treatment in solid tumors) and decreased to 27% at the end of treatment (beginning of maintenance in acute leukemia and completion of planned treatment in solid tumors) (P = 0.0005). There was no significant difference in nutritional status between patients with hematological malignancies and solid tumors (P = 0.8). CONCLUSION: Under nutrition is present in close to half of the pediatric cancer patients presenting to our institute. Active nutritional intervention and education were able to significantly reduce the prevalence of under-nutrition in patients at the end of treatment. PMID- 26853407 TI - Utility of ultrasonic scalpel for axillary dissection in a patient with permanent cardiac pacemakers. PMID- 26853408 TI - Nutritional status at presentation, comparison of assessment tools, and importance of arm anthropometry in children with cancer in India. AB - BACKGROUND: In India, approximately 40,000 new cases of cancer in children are diagnosed each year. However, there are no good studies analyzing their nutritional status. Also, since accurate and sensitive nutritional assessment is critical for optimal clinical outcomes through timely remediation of malnutrition, it is important to assess the relative sensitivity and feasibility of commonly used nutritional screening tools. METHODS: This observational study analyzed height/length (cm), weight (kg), mid-upper arm circumference (MUAC), triceps skinfold thickness (TSFT) as well as their Z-scores or percentiles, albumin levels and history of weight loss at diagnosis in children aged 2-15 years being treated for cancer between November 2008 to December 2013. Body mass index (BMI) and arm muscle circumference (AMC) were calculated respectively from height and weight, and MUAC and TSFT. RESULTS: A total of 1693 new patients were enrolled; 1187 had all anthropometric measurements performed. The prevalence of malnutrition was 38%, 57%, 76%, 69% and 81% on the basis of BMI, TSFT, MUAC, AMC, and arm TSFT + MUAC respectively with the highest prevalence in solid abdominal tumours. Addition of BMI and serum albumin to arm anthropometry increased the proportion classified as severely nutritionally depleted by a mere 2% & 1.5% respectively. Positive history of significant weight loss additionally identified 16.5% at nutritional risk over arm anthropometry. CONCLUSIONS: The prevalence of malnutrition in Indian children with cancer at presentation is very high ranging from 40% and 80% depending on the method used for assessment, being higher with MUAC and lowest with BMI. Either MUAC alone or TSFT + MUAC (wherever feasible) should be used for screening for malnutrition in children with cancer at diagnosis to plan timely nutritional interventions, reduce the treatment-related morbidity and optimise their chance of long-term cure. PMID- 26853409 TI - Teaching pathology of breast cancer to medical undergraduates by case based learning method. PMID- 26853410 TI - Pneumocytic adenomyoepithelioma in a case of myoepithelial carcinoma of the submandibular gland. PMID- 26853411 TI - Mesenteric adenopathy and malignant ascites in prostatic adenocarcinoma: An unusual presentation. PMID- 26853412 TI - Nutritional status in survivors of childhood cancer: Experience from Tata Memorial Hospital, Mumbai. AB - BACKGROUND: Survivors of childhood cancer are at increased risk for several cardiometabolic complications. Obesity/overweight and metabolic syndrome have been widely reported in Western literature, but data from India are lacking. AIMS: To perform an objective assessment of nutritional status in a cohort of childhood cancer survivors (CCSs) and to find risk factors for extremes in nutritional status. SETTINGS AND DESIGN: The study was a retrospective chart review of CCSs who attended the late effects clinic of a referral pediatric oncology center over the period of 1 year. MATERIALS AND METHODS: An objective assessment of nutritional status was done, and results were analyzed in two groups: Adult survivors (present age <18 years) and child and adolescent survivors (CASs) (<18 years). The data were then analyzed for possible risk factors. RESULTS: Six hundred and forty-eight survivors were included in the study; of these, 471 were <18 years at follow-up, and 177 were 18 years or older. The prevalence of obesity, overweight, normal, and undernutrition was 2.6%, 10.8%, 62.7%, and 28.8% (CASs) and 0%, 8.5%, 62.7%, and 28.8% (adult survivors), respectively. Factors predictive of overweight/obesity were an initial diagnosis of acute lymphoblastic leukemia, or brain tumor and follow-up duration of >20 years or current age >30 years in adult survivors. CONCLUSIONS: The prevalence of obesity/overweight is lower in our cohort when compared to Western literature. It remains to be clarified whether this reflects the underlying undernutrition in our country, or whether our cohort of survivors is indeed distinct from their Western counterparts. Comparison with age/sex-matched normal controls and baseline parameters would yield more meaningful results. PMID- 26853413 TI - Hypothesizing association between cancer cachexia and Fluorodeoxyglucose-positron emission tomography documented brown adipose tissue hypermetabolism in cancer patients with an illustration in grossly emaciated cachectic patient in hot Indian summer climate: Will beta blockers find use in the management of this condition? PMID- 26853414 TI - The development, testing, and preliminary feasibility of an adaptable pediatric oncology nutrition algorithm for low-middle income countries. AB - BACKGROUND: Survivors of childhood cancer are at increased risk for several cardiometabolic complications. Obesity/overweight and metabolic syndrome have been widely reported in Western literature, but data from India are lacking. AIMS: To perform an objective assessment of nutritional status in a cohort of childhood cancer survivors (CCSs) and to find risk factors for extremes in nutritional status. SETTINGS AND DESIGN: The study was a retrospective chart review of CCSs who attended the late effects clinic of a referral pediatric oncology center over the period of 1 year. MATERIALS AND METHODS: An objective assessment of nutritional status was done, and results were analyzed in two groups: Adult survivors (present age <18 years) and child and adolescent survivors (CASs) (<18 years). The data were then analyzed for possible risk factors. RESULTS: Six hundred and forty-eight survivors were included in the study; of these, 471 were <18 years at follow-up, and 177 were 18 years or older. The prevalence of obesity, overweight, normal, and undernutrition was 2.6%, 10.8%, 62.7%, and 28.8% (CASs) and 0%, 8.5%, 62.7%, and 28.8% (adult survivors), respectively. Factors predictive of overweight/obesity were an initial diagnosis of acute lymphoblastic leukemia, or brain tumor and follow-up duration of >20 years or current age >30 years in adult survivors. CONCLUSIONS: The prevalence of obesity/overweight is lower in our cohort when compared to Western literature. It remains to be clarified whether this reflects the underlying undernutrition in our country, or whether our cohort of survivors is indeed distinct from their Western counterparts. Comparison with age/sex-matched normal controls and baseline parameters would yield more meaningful results. PMID- 26853415 TI - Ubiquitous lytic osseous lesions in acute lymphoblastic leukemia: A rare case report. PMID- 26853416 TI - Carcinoma and tuberculosis of the breast coexisting in same breast with axillary lymphadenopathy: A rare association. PMID- 26853417 TI - Carcinoma of the gallbladder presenting with multiple osseous and inguinal lymph node metastases. PMID- 26853418 TI - Circulating tumor cells in oral squamous cell carcinoma: An insight. AB - Circulating tumor cells (CTCs) are those cells present in the blood and have antigenic and/or genetic characteristics of a specific tumor type. CTCs can be detected in the peripheral blood of cancer patients. Various techniques are available for detection of CTCs, which provide evidence for future metastasis. CTCs may provide new insight into the biology of cancer and process of metastasis in oral squamous cell carcinoma (OSCC). The detection of CTCs may represent a new diagnostic tool for predicting the occurrence of metastatic disease in OSCC and endow with the treatment strategies to efficiently treat and prevent cancer metastasis. This review gives an insight into the significance of CTCs and different techniques for detection of CTCs. PMID- 26853419 TI - Ameloblastic carcinoma: An effort to abridge this diagnostic challenge! PMID- 26853420 TI - Design, architecture and application of nanorobotics in oncology. AB - Oncologists all over the globe, relentlessly research on methodologies for detection of cancer and precise localization of cancer therapeutics with minimal adverse effects on healthy tissues. Since the previous decade, the fast growing research in nanotechnology has shown promising possibilities for achieving this dream of every oncologist.Nanorobots (or nanobots) are typical devices ranging in size from 0.1 to 10 MUm and constructed of nanoscale or molecular components. Robots will augment the surgeon's motor performance, diagnostic capability and sensations with haptics and augmented reality. The article here aims in briefly describing the architecture of the nanorobots and their role in oncotherapy. Although, research into nanorobots is still in its preliminary stages, the promise of such technology is endless. PMID- 26853421 TI - The inside mystery of penile leiomyosarcoma. PMID- 26853422 TI - Genomic profiling in a homogeneous molecular subtype of non-small cell lung cancer: An effort to explore new drug targets. AB - BACKGROUND: Patients' who are positive for kinase domain activating mutations in epidermal growth factor receptor (EGFR) gene, constitute 30-40% of non-small cell lung cancer (NSCLC), and are suitable candidates for Tyrosine Kinase Inhibitor based targeted/personalized therapy. In EGFR non-mutated subset, 8-10% that show molecular abnormalities such as EML4-ALK, ROS1-ALK, KIP4-ALK, may also derive the benefit of targeted therapy. However, 40% of NSCLC belong to a grey zone of tumours that are negative for the clinically approved biomarkers for personalized therapy. This pilot study aims to identify and classify molecular subtypes of this group to address the un-met need for new drug targets in this category. Here we screened for known/novel oncogenic driver mutations using a 46 gene Ampliseq Panel V1.0 that includes Ser/Thr/Tyr kinases, transcription factors and tumor suppressors. METHODS: NSCLC with tumor burden of at least 40% on histopathology were screened for 29 somatic mutations in the EGFR kinase domain by real-time polymerase chain reaction methods. 20 cases which were EGFR non-mutated for TK domain mutations were included in this study. DNA Quality was verified from each of the 20 cases by fluorimeter, pooled and subjected to targeted re-sequencing in the Ion Torrent platform. Torrent Suite software was used for next generation sequencing raw data processing and variant calling. RESULTS: The clinical relevance and pathological role of all the mutations/variants that include SNPs and Indels was assessed using polyphen-2/SIFT/PROVEAN/mutation assessor structure function prediction programs. There were 10 pathogenic mutations in six different oncogenes for which annotation was available in the COSMIC database; C420R mutation in PIK3CA, Q472H mutation in vascular endothelial growth factor receptor 2 (VEGFR2) (KDR), C630W and C634R in RET, K367M mutation in fibroblast growth factor receptor 2 (FGFR2), G12C in KRAS and 4 pathogenic mutations in TP53 in the DNA binding domain (E285K, R213L, R175H, V173G). CONCLUSION: Results suggest, a potential role for PIK3CA, VEGFR2, RET and FGFR2 as therapeutic targets in EGFR non-mutated NSCLC that requires further clinical validation. PMID- 26853423 TI - Bone-confined extensive disease as the presentation of disease recurrence in the setting of malignant transformation of pleomorphic adenoma of parotid gland with excellent locoregional control: Value of whole body skeletal survey. PMID- 26853424 TI - Could ingenol mebutate be useful in managing nonmelanoma skin cancers? PMID- 26853425 TI - Heterozygosity of stromelysin-1 (rs3025058) promoter polymorphism is associated with gastric cancer. AB - BACKGROUND: Gastric cancer (GC) is the third most common cancer in India and is mediated by multiple genetic, epigenetic and environmental risk factors. A single nucleotide polymorphism rs3025058 at -1171 of the stromelysin-1 (matrix metalloproteinase [MMP]-3) promoter is resulting due to insertion/deletion of adenine thought to have an impact on increasing the risk for tumor formation. AIM: This study is aimed to understand the role of stromelysin-1 rs3025058 ( 1171, 5A/6A) promoter polymorphism in the etiology of GC in Indian population. MATERIALS AND METHODS: Genomic DNA was isolated from blood samples of the GC patients and controls. The genotyping of stromelysin-1 rs3025058 (-1171, 5A/6A) promoter polymorphism was carried out by amplification refractory mutation system polymerase chain reaction method followed by agarose gel electrophoresis. RESULTS: The frequency of 5A/5A, 5A/6A, and 6A/6A genotypes in GC patients were 7.69%, 76.92%, and 15.38%, while in controls were 5.31%, 86.73%, and 7.96%, respectively. There was a significant difference in the distribution of 5A/6A genotype in patients compared to the controls (P < 0.05). CONCLUSION: This study showed an increased frequency of heterozygotes for stromelysin-1 rs3025058 and thought to be involved in the etiology of GC. PMID- 26853426 TI - Primary undifferentiated spindle cell sarcoma of the lung with metastasis to bone -A rare clinical entity with even rarer clinical course. PMID- 26853427 TI - Construction of Spirocyclic Oxindoles through Regio- and Stereoselective [3+2] or [3+2]/[4+2] Cascade Reaction of alpha,beta-Unsaturated Imines with 3 Isothiocyanato Oxindole. AB - On the basis of asymmetric regioselective [3+2] or [3+2]/[4+2] cascade reaction of 3-isothiocyanato oxindoles with C=C and C=N bonds of alpha,beta-unsaturated methanesulfonamides, diversified S-containing heterocyclic spirooxindole derivatives could be obtained in high yields along with good to excellent diastereo- and enantioselectivities under mild conditions in the presence of cinchona alkaloid-derived organocatalysts. PMID- 26853428 TI - Tumour-associated antigens and their anti-cancer applications. AB - So far, a number of tumour-associated antigens (TAAs), such as heat shock proteins, alpha-fetoprotein, carcino-embryonic antigen and others have been identified in a variety of malignant tumours. Differences in the expression levels of TAAs in cancers compared with normal cells have led to these antigens being investigated as diagnostic and prognostic biomarkers or exciting targets in cancer treatment. Here, we systematically list the current representative TAAs to shed some light on current approaches and challenges for their anti-cancer application in cancer therapy. In this review, we discuss the ongoing pre clinical studies and clinical development of TAAs in human cancers, and the potential application of these TAAs in the diagnosis and prognosis for cancer treatment. PMID- 26853429 TI - Comparison of methods for identifying small-for-gestational-age infants at risk of perinatal mortality among obese mothers: a hospital-based cohort study. AB - OBJECTIVE: To assess differences in small-for-gestational age (SGA) classifications for the detection of neonates with increased perinatal mortality risk among obese women and subsequently assess the association between prepregnancy body mass index (BMI) status and SGA. DESIGN: Hospital-based cohort. SETTING: Twelve US clinical centres (2002-08). POPULATION: A total of 114 626 singleton, nonanomalous pregnancies. METHODS: Data were collected using electronic medical record abstraction. Relative risks (RR) with 95% CI were estimated. MAIN OUTCOME MEASURES: SGA trends (birthweight < 10th centile) classified using population-based (SGAPOP ), intrauterine (SGAIU ) and customised (SGACUST ) references were assessed. The SGA-associated perinatal mortality risk was estimated among obese women. Using the SGA method most associated with perinatal mortality, the association between prepregnancy BMI and SGA was estimated. RESULTS: The overall perinatal mortality prevalence was 0.55% and this increased significantly with increasing BMI (P < 0.01). Among obese women, SGAIU detected the highest proportion of perinatal mortality cases (2.49%). Perinatal mortality was 5.32 times (95% CI 3.72-7.60) more likely among SGAIU neonates than non-SGAIU neonates. This is in comparison with the 3.71-fold (2.49-5.53) and 4.81 fold (3.41-6.80) increased risk observed when SGAPOP and SGACUST were used, respectively. Compared with women of normal weight, overweight women (RR = 0.82, 95% CI 0.78-0.86) and obese women (RR = 0.80; 95% CI 0.75-0.83) had a lower risk for delivering an SGAIU neonate. CONCLUSION: Among obese women, the intrauterine reference best identified neonates at risk of perinatal mortality. Based on SGAIU , SGA is less common among obese women but these SGA babies are at a high risk of death and remain an important group for surveillance. TWEETABLE ABSTRACT: SGA is less common among obese women but these SGA babies are at a high risk of death. PMID- 26853430 TI - Can response to dietary restriction predict weight loss after Roux-en-Y gastroplasty? AB - OBJECTIVE: To determine whether weight loss (WL) with 6 weeks of a low-calorie liquid diet as part of a behavioral program (LCDBP) predicts subsequent weight change in response to a laparoscopic Roux-en-Y gastric bypass (RYGB). METHODS: Of 4698 LCDBP patients, 403 went on to RYGB and 222 were evaluable. We determined correlations between percent WL (% WL) in 6 weeks of LCDBP with % WL at 4, 12, 24, 36, and 52 weeks after RYGB. RESULTS: There was a positive correlation between the slope of WL in the first 6 weeks of LCDBP and over 4 and 12 weeks after RYGB: r = 0.15 (CI = 0.003-0.285, P = 0.045) and r = 0.22 (CI = 0.08-0.35, P = 0.0017), respectively. The association was also apparent at 24 weeks in females but not in males. There was a statistically significant correlation between % WL at 26 weeks of LCDBP and 52 weeks postsurgery (r = 0.20, CI = 0.05 0.34, P = 0.01). Finally, % WL at 6 weeks also predicted % WL at 26 weeks of dietary intervention (r = 0.52, CI = 0.40-0.62, P = 2.40 * 10(-14) ). CONCLUSIONS: WL in response to 6 weeks of LCDBP is predictive of weight for at least 12 weeks following RYGB. PMID- 26853431 TI - Decreasing the dispatch time of medical reports sent from hospital to primary care with Lean Six Sigma. AB - RATIONALE, AIMS AND OBJECTIVES: Timely communication is important to ensure high quality health care. To facilitate this, the Gastro Intestinal Oncology Center Amsterdam (GIOCA) stipulated to dispatch medical reports on the day of the patient's visit. However, with the increasing number of patients, administrative processes at GIOCA were under pressure, and this standard was not met for the majority of patients. The aim and objective of this study was to dispatch 90% of medical reports on the day of the patient's visit by improving the logistic process. METHODS: To assess the main causes for a prolonged dispatch time and to design improvements actions, the roadmap offered by Lean Six Sigma (LSS) was used, consisting of five phases: Define, Measure, Analyze, Improve and Control (DMAIC roadmap). RESULTS: Initially, 12.3% of the reports were dispatched on the day of the patient's visit. Three causes for a prolonged dispatch time were identified: (1) determining which doctors involved with treatment would compose the report; (2) the reports composed by a senior resident had to be reviewed by a medical specialist; and (3) a medical specialist had to authorize the administration to dispatch the reports. To circumvent these causes, a digital form was implemented in the electronic medical record that could be completed during the multidisciplinary team meeting. After implementation, 90.6% of the reports were dispatched on the day of the visit. CONCLUSION: The dispatch time of reports sent from hospital to primary care can be significantly reduced using Lean Six Sigma, improving the communication between hospital and primary care. PMID- 26853432 TI - Cdk5-Dependent Activation of Neuronal Inflammasomes in Parkinson's Disease. AB - BACKGROUND: Inflammasomes, which mediate the activation of caspase-1 and maturation of IL-1beta and IL-18, have been unambiguously verified to participate in many diseases, such as lung diseases, infectious diseases and Alzheimer's disease, but the relation between Parkinson's disease and inflammasomes is poorly understood. METHODS: The expression, maturation, and secretion of inflammasomes in neurons were measured. The activation of inflammasomes in the substantia nigra of the brain was tested in acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and an alpha-synuclein transgenic mouse model. The levels of IL-1beta and IL-18 in cerebrospinal fluid and serum samples of Parkinson's disease (PD) patients and control subjects were measured. The role of cyclin-dependent kinase 5 (Cdk5) in neuronal inflammasome activation was evaluated using the pharmacological Cdk5 inhibitor roscovitine or Cdk5-targeted deletion. RESULTS: Here, we observed the expression of core molecules of inflammasomes, including NALP3, ASC, caspase-1, and IL-1beta, in neuronal cells. The PD inducer rotenone could activate neuronal inflammasomes and promote the maturation and secretion of the cleaved IL-1beta and IL-18 in a dose- and time-dependent manner. We also detected the activation of inflammasomes in the substantia nigra of a PD mouse model and in cerebrospinal fluid of PD patients. Furthermore, Cdk5 is required for the activation of inflammasomes, and both inhibition and deletion of Cdk5 could efficiently block inflammasome activation in PD models. CONCLUSIONS: Together, our results indicated that Cdk5-dependent activation of neuronal inflammasomes was involved in the progression of PD. PMID- 26853433 TI - Structure-function studies of HNF1A (MODY3) gene mutations in South Indian patients with monogenic diabetes. AB - Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of diabetes characterized by onset of diabetes below 25 years of age, autosomal dominant mode of inheritance and primary defect in insulin secretion. Mutations in the gene (HNF1A) encoding transcription factor hepatocyte nuclear factor 1A (HNF-1A) results in one of the most common forms of MODY (MODY3). HNF-1A is mainly enriched in pancreatic beta-cells and hepatocytes and important for organ development and normal pancreatic function. We here report on the functional interrogation of eight missense HNF1A mutations associated with MODY3 in South Indian subjects, and the contributing effect of common variant (S487N) within HNF1A. Of the eight mutations, three mutations (p.R171G, p.G245R and p.R263H), in particular, affected HNF-1A function in transfected HeLa cells by reducing both transcriptional activity and nuclear localization, possibly due to disruption of the integrity of the three dimensional structure. The common variant p.S487N contributed further to the loss-of-function of p.R271Q (p.R271Q+p.S487N double mutant), in vitro, on both activity and localization. Our data on the first functional study of HNF1A mutations in South India subjects confers that the defect of the HNF-1A mutant proteins are responsible for MODY3 diabetes in these patients. PMID- 26853434 TI - Identifying developmental phases in the Arabidopsis thaliana rosette using integrative segmentation models. AB - The change in leaf size and shape during ontogeny associated with heteroblastic development is a composite trait for which extensive spatiotemporal data can be acquired using phenotyping platforms. However, only part of the information contained in such data is exploited, and developmental phases are usually defined using a selected organ trait. We here introduce new methods for identifying developmental phases in the Arabidopsis rosette using various traits and minimum a priori assumptions. A pipeline of analysis was developed combining image analysis and statistical models to integrate morphological, shape, dimensional and expansion dynamics traits for the successive leaves of the Arabidopsis rosette. Dedicated segmentation models called semi-Markov switching models were built for selected genotypes in order to identify rosette developmental phases. Four successive developmental phases referred to as seedling, juvenile, transition and adult were identified for the different genotypes. We show that the degree of covering of the leaf abaxial surface with trichomes is insufficient to define these developmental phases. Using our pipeline of analysis, we were able to identify the supplementary seedling phase and to uncover the structuring role of various leaf traits. This enabled us to compare on a more objective basis the vegetative development of Arabidopsis mutants. PMID- 26853436 TI - Predictive approach for protein aggregation: Correlation of protein surface characteristics and conformational flexibility to protein aggregation propensity. AB - The aggregation of proteins became one of the major challenges in the development of biopharmaceu-ticals since the formation of aggregates can affect drug quality and immunogenicity. However, aggregation mechanisms are highly complex and the investigation requires cost, time, and material intensive experi-mental effort. In the present work, the predictive power of protein characteristics for the phase behavior of three different proteins which are very similar in size and structure was studied. In particular, the surface hydrophobicity, zeta potential, and conformational flexibility of human lysozyme, lysozyme from chicken egg white, and alpha-lactalbumin at pH 3, 5, 7, and 9 were assessed and examined for correlation with experimental stability studies focusing on protein phase behavior induced by sodium chloride and ammonium sulfate. The molecular dynamics (MD) simulation based study of the conformational flexibility without precipitants was able to identify highly flexible protein regions which could be associated to the less regular secondary structure elements and random coiled and terminal regions in particular. Conformational flex-ibility of the entire protein structure and protein surface hydrophobicity could be correlated to differing aggregation propensities among the studied proteins and could be identified to be applicable for predic-tion of protein phase behavior in aqueous solution without precipitants. For prediction of protein phase behavior and aggregation propensity in aqueous solution with precipitants, protein flexibility was further studied in dependency of salt concentration and species by means of human lysozyme. Even though the results of the salt dependent MD simulations could not be shown to be sufficient for prediction of salt depending phase behavior, this study revealed a more pronounced destabilizing effect of ammonium sulfate in comparison to sodium chloride and thus, was found to be in good agreement with theoretical considerations along the Hofmeister series as well as experimentally evaluated phase behavior. Biotechnol. Bioeng. 2017;114: 1170-1183. (c) 2016 Wiley Periodicals, Inc. PMID- 26853435 TI - Comparative analysis of Cu (I)-catalyzed alkyne-azide cycloaddition (CuAAC) and strain-promoted alkyne-azide cycloaddition (SPAAC) in O-GlcNAc proteomics. AB - O-linked beta-N-acetylglucosamine (O-GlcNAc) is emerging as an essential protein post-translational modification in a range of organisms. It is involved in various cellular processes such as nutrient sensing, protein degradation, gene expression, and is associated with many human diseases. Despite its importance, identifying O-GlcNAcylated proteins is a major challenge in proteomics. Here, using peracetylated N-azidoacetylglucosamine (Ac4 GlcNAz) as a bioorthogonal chemical handle, we described a gel-based mass spectrometry method for the identification of proteins with O-GlcNAc modification in A549 cells. In addition, we made a labeling efficiency comparison between two modes of azide-alkyne bioorthogonal reactions in click chemistry: copper-catalyzed azide-alkyne cycloaddition (CuAAC) with Biotin-Diazo-Alkyne and stain-promoted azide-alkyne cycloaddition (SPAAC) with Biotin-DIBO-Alkyne. After conjugation with click chemistry in vitro and enrichment via streptavidin resin, proteins with O-GlcNAc modification were separated by SDS-PAGE and identified with mass spectrometry. Proteomics data analysis revealed that 229 putative O-GlcNAc modified proteins were identified with Biotin-Diazo-Alkyne conjugated sample and 188 proteins with Biotin-DIBO-Alkyne conjugated sample, among which 114 proteins were overlapping. Interestingly, 74 proteins identified from Biotin-Diazo-Alkyne conjugates and 46 verified proteins from Biotin-DIBO-Alkyne conjugates could be found in the O GlcNAc modified proteins database dbOGAP (http://cbsb.lombardi.georgetown.edu/hulab/OGAP.html). These results suggested that CuAAC with Biotin-Diazo-Alkyne represented a more powerful method in proteomics with higher protein identification and better accuracy compared to SPAAC. The proteomics credibility was also confirmed by the molecular function and cell component gene ontology (GO). Together, the method we reported here combining metabolic labeling, click chemistry, affinity-based enrichment, SDS PAGE separation, and mass spectrometry, would be adaptable for other post translationally modified proteins in proteomics. PMID- 26853437 TI - Oral health screening: feasibility and reliability of the oral health assessment tool as used by speech pathologists. AB - BACKGROUND: The aim of this study was to investigate the feasibility and reliability of the Oral Health Assessment Tool (OHAT) as used by speech pathologists, to become part of a comprehensive clinical swallowing examination. METHODS: A multicentre study in 132 elderly subjects was conducted by speech pathologists. The inter-rater, test-retest and intra-rater reliabilities of the OHAT were assessed in R statistics, version 3.0.1. Intraclass correlation coefficients (ICCs) were used for the total OHAT, and Kappa statistics were used for the individual categories. RESULTS: Total OHAT scores showed good inter-rater (ICC = 0.96), intra-rater (ICC >= 0.95) and test-retest (ICC >= 0.78) agreement. The inter-rater Kappa statistics were almost perfect (kappa >= 0.83) for seven of the eight individual categories of the OHAT and perfect for 'dental pain' (kappa = 1.00). The test-retest Kappa statistics indicated excellent agreement for 'natural teeth' and 'dentures' (kappa >= 0.86). The intra-rater per cent agreement was excellent for all categories except 'gums and tissues'. CONCLUSIONS: This is the first study to examine the feasibility and reliability of the OHAT as used by speech pathologists. As the results showed both good feasibility and reliability, the OHAT has the potential to add to the clinical swallowing examination. However, future research investigating actual referral strategies and adaptation of care strategies following assessment with OHAT is needed. PMID- 26853438 TI - Stabilization of Organic-Inorganic Perovskite Layers by Partial Substitution of Iodide by Bromide in Methylammonium Lead Iodide. AB - Thin films of the methylammonium lead halides CH3 NH3 Pb(I1-x Brx )3 are prepared on fluorine-doped tin oxide substrates and exposed to humid air in the dark and under illumination. To characterize the stability of the materials, UV/Vis spectra are acquired at fixed intervals, accompanied by XRD, energy-dispersive X ray spectroscopy, SEM, and confocal laser scanning microscopy. Different degradation mechanisms are observed depending on the environmental conditions. It is found that bromide can successfully suppress the transformation of the perovskite into the monohydrate, presumably owing to stronger hydrogen-bonding interactions with the organic cation. However, under illumination in humid air, rather rapid decomposition of the perovskites was still observed, which is due to phase segregation. The use of increased bromide content in methylammonium lead halide absorbers is discussed in terms of their application in perovskite solar cells. PMID- 26853439 TI - Multisensory Stop Signals Can Reduce the Disinhibiting Effects of Alcohol in Adults. AB - BACKGROUND: Alcohol impairs drinkers' abilities to inhibit inappropriate responses. Certain stimulus conditions have been shown to facilitate behavioral control. Under conditions where individuals are presented with multiple inhibitory signals, the speed and consistency with which they are able to inhibit a response is improved. Recent research has shown that multisensory signals might protect against the disruptive effects of alcohol on mechanisms of behavioral control. This study examined whether multisensory stop signals can be used to improve inhibitory control, possibly by speeding attentional shifts toward inhibitory "stop" signals in the environment. METHODS: Twenty adult social drinkers performed a modified cued go/no-go task that measured the ability to inhibit prepotent responses following 0.64 g/kg alcohol and placebo. Response targets were presented as unimodal (visual) and as multisensory (visual + aural) stimuli. RESULTS: Results showed that during unimodal response target trials, participants made more inhibitory failures under 0.64 g/kg alcohol compared to placebo. During multisensory trials, however, there was no significant effect of alcohol on inhibitory control. CONCLUSIONS: These findings identify multisensory inhibitory signals as a potentially important environmental factor that can reduce the degree to which alcohol disinhibits behavior possibly by intersensory co-activation between the visual and auditory pathways. PMID- 26853440 TI - Guidelines for the diagnosis and treatment of acute non-variceal upper gastrointestinal bleeding (2015, Nanchang, China). AB - Acute non-variceal upper gastrointestinal bleeding (ANVUGIB) is one of the most common medical emergencies in China and worldwide. In 2009, we published the "Guidelines for the diagnosis and treatment of acute non-variceal upper gastrointestinal bleeding" for the patients in China; however, during the past years numerous studies on the diagnosis and treatment of ANVUGIB have been conducted, and the management of ANVUGIB needs to be updated. The guidelines were updated after the databases including PubMed, Embase and CNKI were searched to retrieve the clinical trials on the management of ANVUGIB. The clinical trials were evaluated for high-quality evidence, and the advances in definitions, diagnosis, etiology, severity evaluation, treatment and prognosis of ANVUGIB were carefully reviewed, the recommendations were then proposed. After several rounds of discussions and revisions among the national experts of digestive endoscopy, gastroenterology, radiology and intensive care, the 2015 version of "Guidelines for the diagnosis and treatment of acute non-variceal upper gastrointestinal bleeding" was successfully developed by the Chinese Journal of Internal Medicine, National Medical Journal of China, Chinese Journal of Digestion and Chinese Journal of Digestive Endoscopy. It shall be noted that although much progress has been made, the clinical management of ANVUGIB still needs further improvement and refinement, and high-quality randomized trials are required in the future. PMID- 26853441 TI - Synthesis and Pharmacological Activity of a New Series of 1-(1H-Indol-4-yloxy)-3 (2-(2-methoxyphenoxy)ethylamino)propan-2-ol Analogs. AB - beta-Adrenergic receptor antagonists are important therapeutics for the treatment of cardiovascular disorders. In the group of beta-blockers, much attention is being paid to the third-generation drugs that possess important ancillary properties besides inhibiting beta-adrenoceptors. Vasodilating activity of these drugs is produced through different mechanisms, such as nitric oxide (NO) release, beta2 -agonistic action, alpha1 -blockade, antioxidant action, and Ca(2+) entry blockade. Here, a study on evaluation of the cardiovascular activity of five new compounds is presented. Compound 3a is a methyl and four of the tested compounds (3b-e) are dimethoxy derivatives of 1-(1H-indol-4-yloxy)-3-(2-(2 methoxyphenoxy)ethylamino)propan-2-ol. The obtained results confirmed that the methyl and dimethoxy derivatives of 1-(1H-indol-4-yloxy)-3-(2-(2 methoxyphenoxy)ethylamino)propan-2-ol and their enantiomers possess alpha1 - and beta1 -adrenolytic activities and that the antiarrhythmic and hypotensive effects of the tested compounds are related to their adrenolytic properties. PMID- 26853442 TI - P2X1-regulated IL-22 secretion by innate lymphoid cells is required for efficient liver regeneration. AB - Paracrine signalling mediated by cytokine secretion is essential for liver regeneration after hepatic resection, yet the mechanisms of cellular crosstalk between immune and parenchymal cells are still elusive. Interleukin-22 (IL-22) is released by immune cells and mediates strong hepatoprotective functions. However, it remains unclear whether IL-22 is critical for the crosstalk between liver lymphocytes and parenchymal cells during liver regeneration after partial hepatectomy (PH). Here, we found that plasma levels of IL-22 and its upstream cytokine, IL-23, are highly elevated in patients after major liver resection. In a mouse model of PH, deletion of IL-22 was associated with significantly delayed hepatocellular proliferation and an increase of hepatocellular injury and endoplasmic reticulum stress. Using Rag1(-/-) and Rag2(-/-) gammac(-/) (-) mice, we show that the main producers of IL-22 post-PH are conventional natural killer cells and innate lymphoid cells type 1. Extracellular adenosine triphosphate (ATP), a potent danger molecule, is elevated in patients immediately after major liver resection. Antagonism of the P2-type nucleotide receptors, P2X1 and P2Y6, significantly decreased IL-22 secretion ex vivo. In vivo, specific inhibition of P2X1 was associated with decreased IL-22 secretion, elevated liver injury, and impaired liver regeneration. CONCLUSION: This study shows that innate immune cell derived IL-22 is required for efficient liver regeneration and that secretion of IL-22 in the regenerating liver is modulated by the ATP receptor, P2X1. (Hepatology 2016;63:2004-2017). PMID- 26853444 TI - Anxiety in common situations of everyday life and depression in women with mastectomies. PMID- 26853443 TI - Coding region variant 186H/R in Exon 4 of APOBEC3G among individuals of Western India. AB - The allelic variations in the AIDS restriction genes have been associated with the acquisition of HIV-1 and its progression. The distribution of antiviral gene variants significantly differs between populations. Therefore, we aimed to evaluate the distribution of variant allele of 186H/R in exon4 of APOBEC3G between HIV infected individuals and healthy controls among western Indian.In the present cross-sectional study, we enrolled a total of 153 HIV-infected patients confirmed and 156 unrelated healthy individuals. Polymorphism for 186H/R in exon4 of APOBEC3G gene was genotyped by PCR-RFLP. With the frequency of 186HR heterozygous genotype of APOBEC3G was found to be 13% in healthy controls and none in HIV infected cases. The frequency of 186HH common genotype of APOBEC3G was observed higher in HIV infected individuals compared with healthy controls (100% vs 91.7%). The variant genotype 186RR in APOBEC3G was not found in both the groups. The frequency of 186R allele of APOBEC3G was found 4.16% in healthy controls and nil in HIV-infected cases. The frequency of 186H allele of APOBEC3G was found to be higher in HIV-infected cases compared with healthy controls (100% vs 95.83%). The frequency of 186R allele in exon4 of APOBEC3G was found to be 4.16% in healthy controls. This observation differs from the previous report published from North India stating the absence of 186R allele of APOBEC3G in the North Indian individuals. The variant 186H/R in exon4 of APOBEC3G was neither associated with risk of acquisition of HIV-1 nor its progression. PMID- 26853445 TI - Thyroid hormone therapy and procurement of livers from brain-dead donors. AB - Hormonal therapy to brain-dead potential organ donors remains controversial. A retrospective study was carried out of hormonal therapy on procurement of organs in 63,593 donors in whom information on T3/T4 therapy was available. In 40,124 donors, T3/T4 and all other hormonal therapy was recorded. The percentages of all organs procured, except livers, were greater in T3/T4-treated donors. Nevertheless, if T3/T4 therapy had been administered to the donor, liver transplantation was associated with significantly increased graft and recipient survival at 1 month and 12 months. The potential reasons for the lack of effect of T3/T4 therapy on the number of livers procured are discussed. PMID- 26853446 TI - Normative data on audiovisual speech integration using sentence recognition and capacity measures. AB - OBJECTIVE: The ability to use visual speech cues and integrate them with auditory information is important, especially in noisy environments and for hearing impaired (HI) listeners. Providing data on measures of integration skills that encompass accuracy and processing speed will benefit researchers and clinicians. DESIGN: The study consisted of two experiments: First, accuracy scores were obtained using City University of New York (CUNY) sentences, and capacity measures that assessed reaction-time distributions were obtained from a monosyllabic word recognition task. STUDY SAMPLE: We report data on two measures of integration obtained from a sample comprised of 86 young and middle-age adult listeners: RESULTS: To summarize our results, capacity showed a positive correlation with accuracy measures of audiovisual benefit obtained from sentence recognition. More relevant, factor analysis indicated that a single-factor model captured audiovisual speech integration better than models containing more factors. Capacity exhibited strong loadings on the factor, while the accuracy based measures from sentence recognition exhibited weaker loadings. CONCLUSIONS: Results suggest that a listener's integration skills may be assessed optimally using a measure that incorporates both processing speed and accuracy. PMID- 26853447 TI - Emerging importance of dietary phytochemicals in fight against cancer: Role in targeting cancer stem cells. AB - Recent years have seen an unpretending increase in research using dietary phytochemicals for targeting cancer and cancer stem cells (CSCs) due to the limited efficacy of conventional chemotherapy and radiotherapy and numerous associated side effects. A large number of dietary phytochemicals using traditional recommendation and experimental approaches have been demonstrated to have anti-proliferative, anti-metastatic, reactive oxygen species (ROS) inducing, anti-angiogenic, pro-apoptotic effects and efficacy in targeting cellular molecules and pathways implicated in malignancy. Researchers have shown the knack of phytochemicals in interfering with the CSCs self-renewal process. Thus, dietary phytochemicals can play a significant role in the cancer therapy owing to the plethora of targets without toxicity. In this review, we have discussed about the basic knowledge of CSCs, their identification, characterization, mechanism of self-renewal pathways (Wnt/beta-catenin, Hedgehog, and Notch), features that help in the survival of CSCs and use of phytochemicals to replace chemotherapy. Applications of phytochemicals including curcumin, epigallocatechin-3-gallate (EGCG), resveratrol, lycopene, and sulforaphane for their effect on targeting cancer and in particular CSCs along with their molecular mechanisms responsible for pharmacological action are also discussed. PMID- 26853448 TI - Ligands for Ser/Thr phosphoprotein phosphatases: a patent review (2005-2015). AB - INTRODUCTION: The role played by phosphoprotein phosphatases (PPP) enzymes makes them of interest as therapeutic targets to treat pathologies including neurodegenerative diseases, cancer and autoimmune diseases, but also liable to cause severe side effects. This fact has hindered the study of PPP ligands as potential drugs. Fortunately, recent advances in the comprehension of PPP biochemistry have given rise to the development of refined pharmacological strategies to selectively target phosphatases and limit the possible generation of adverse reactions. AREAS COVERED: This review summarizes the most relevant patents claiming the use of PPP ligands to treat human diseases in the last decade (2005-2015). It also includes some pharmacological strategies aiming to indirectly modulate PPP functionality by interacting with PPP-regulating enzymes. EXPERT OPINION: There is still much work to be done to validate PPP enzymes as eligible targets for the development of new drugs. The most significant barrier is likely to be persuading the majority of the scientific community that PPP enzymes are not too unspecific. Few patents disclosed the rational design of direct PPP ligands, while many inventions relied on long chain peptides-based approaches. Overall, the future of ligands for PPP enzymes as therapeutics seems both challenging and exciting. PMID- 26853449 TI - In Vivo Host Response and Degradation of Copolymer Scaffolds Functionalized with Nanodiamonds and Bone Morphogenetic Protein 2. AB - The aim is to evaluate the effect of modifying poly[(l-lactide)-co-(epsilon caprolactone)] scaffolds (PLCL) with nanodiamonds (nDP) or with nDP+physisorbed BMP-2 (nDP+BMP-2) on in vivo host tissue response and degradation. The scaffolds are implanted subcutaneously in Balb/c mice and retrieved after 1, 8, and 27 weeks. Molecular weight analysis shows that modified scaffolds degrade faster than the unmodified. Gene analysis at week 1 shows highest expression of proinflammatory markers around nDP scaffolds; although the presence of inflammatory cells and foreign body giant cells is more prominent around the PLCL. Tissue regeneration markers are highly expressed in the nDP+BMP-2 scaffolds at week 8. A fibrous capsule is detectable by week 8, thinnest around nDP scaffolds and at week 27 thickest around PLCL scaffolds. mRNA levels of ALP, COL1alpha2, and ANGPT1 are significantly upregulating in the nDP+BMP-2 scaffolds at week 1 with ectopic bone seen at week 8. Even when almost 90% of the scaffold is degraded at week 27, nDP are observable at implantation areas without adverse effects. In conclusion, modifying PLCL scaffolds with nDP does not aggravate the host response and physisorbed BMP-2 delivery attenuates inflammation while lowering the dose of BMP-2 to a relatively safe and economical level. PMID- 26853450 TI - Tuned by metals: the TET peptidase activity is controlled by 3 metal binding sites. AB - TET aminopeptidases are dodecameric particles shared in the three life domains involved in various biological processes, from carbon source provider in archaea to eye-pressure regulation in humans. Each subunit contains a dinuclear metal site (M1 and M2) responsible for the enzyme catalytic activity. However, the role of each metal ion is still uncharacterized. Noteworthy, while mesophilic TETs are activated by Mn(2+), hyperthermophilic TETs prefers Co(2+). Here, by means of anomalous x-ray crystallography and enzyme kinetics measurements of the TET3 aminopeptidase from the hyperthermophilic organism Pyrococcus furiosus (PfTET3), we show that M2 hosts the catalytic activity of the enzyme, while M1 stabilizes the TET3 quaternary structure and controls the active site flexibility in a temperature dependent manner. A new third metal site (M3) was found in the substrate binding pocket, modulating the PfTET3 substrate preferences. These data show that TET activity is tuned by the molecular interplay among three metal sites. PMID- 26853451 TI - Changes in the markers of cardiac damage in men following long-distance and ultra long-distance running races. AB - BACKGROUND: The aim of this study was to compare pre- and postcompetition markers of cardiac damage in ultraendurance athletes. METHODS: All the subjects had blood samples collected before starting and immediately after completing the running race, in order to analyze CK, hs-CRP, cTnI, and NT-proBNP. RESULTS: Before starting the marathon, there were no differences between the groups for all of the tests. CK was significantly higher after the 308 km ultra-marathon than after the marathon and the 100 km ultra-marathon (P<0.001). In cTnI, the value after the 100 km ultra-marathon was significantly higher than that after the marathon and 308 km ultra-marathon, respectively (P<0.05, P<0.01). NT-proBNP was significantly higher after the 100 km and 308 km ultra-marathons than after the marathon (P<0.01, P<0.01). Hs-CRP was significantly higher after the 308 km ultra marathon than after the marathon and the 100 km ultra-marathon (P<0.001). CONCLUSIONS: cTnI was expressed after marathon and the 100 km ultra-marathon, and NT-proBNP exceeding the upper reference limit (URL) was expressed in long distance races such as the 100 km and 308 km ultra-marathons. The highest expression of cTnI and NT-proBNP exceeding the URL was in the 100 km ultra marathon, which may be caused by a combination of the moderate intensity of the exercise and the long-running distance. PMID- 26853453 TI - Reference intervals for mean platelet volume and immature platelet fraction determined on a sysmex XE5000 hematology analyzer. AB - BACKGROUND: New parameters describing the platelet population of the blood are mean platelet volume (MPV), which is a crude estimate of thrombocyte reactivity, and immature platelet fraction (IPF), which reflects megakaryopoietic activity. This study aimed to define reference intervals for MPV and IPF and to investigate whether separate reference intervals according to smoking status, age or sex are necessary. METHODS: Blood samples were obtained from subjects participating in The Danish General Suburban Population Study. MPV and IPF measurements were performed by the use of the Sysmex XE-5000 hematology analyzer. Reference intervals were established by a non-parametric method. RESULTS: In total, 1674 apparently healthy individuals (910 females and 764 males) were included. No significant age, sex or smoking status difference was observed. The reference interval was 9.6-13.1 fL for MPV and 1.3-9.0% for IPF, respectively. CONCLUSION: We have generated reference intervals for MPV and IPF in a large, adult Danish population and found those parameters remarkably stable across age, sex and smoking status. PMID- 26853452 TI - The point of no return: The poly(A)-associated elongation checkpoint. AB - Cyclin-dependent kinases play critical roles in transcription by RNA polymerase II (pol II) and processing of the transcripts. For example, CDK9 regulates transcription of protein-coding genes, splicing, and 3' end formation of the transcripts. Accordingly, CDK9 inhibitors have a drastic effect on the production of mRNA in human cells. Recent analyses indicate that CDK9 regulates transcription at the early-elongation checkpoint of the vast majority of pol II transcribed genes. Our recent discovery of an additional CDK9-regulated elongation checkpoint close to poly(A) sites adds a new layer to the control of transcription by this critical cellular kinase. This novel poly(A)-associated checkpoint has the potential to powerfully regulate gene expression just before a functional polyadenylated mRNA is produced: the point of no return. However, many questions remain to be answered before the role of this checkpoint becomes clear. Here we speculate on the possible biological significance of this novel mechanism of gene regulation and the players that may be involved. PMID- 26853454 TI - Direct observation of charge state in the quasi-one-dimensional conductor Li0.9Mo6O17. AB - The quasi-one-dimensional conductor Li0.9Mo6O17 has been of great interest because of its unusual properties. It has a conducting phase with properties different from a simple Fermi liquid, a poorly understood "insulating" phase as indicated by a metal-"insulator" crossover (a mystery for over 30 years), and a superconducting phase which may involve spin triplet Cooper pairs as a three dimensional (p-wave) non-conventional superconductor. Recent evidence suggests a density wave (DW) gapping regarding the metal-"insulator" crossover. However, the nature of the DW, such as whether it is due to the change in the charge state or spin state, and its relationship to the dimensional crossover and to the spin triplet superconductivity, remains elusive. Here by performing (7)Li-/(95)Mo nuclear magnetic resonance (NMR) spectroscopy, we directly observed the charge state which shows no signature of change in the electric field gradient (nuclear quadrupolar frequency) or in the distribution of it, thus providing direct experimental evidences demonstrating that the long mysterious metal-"insulator" crossover is not due to the charge density wave (CDW) that was thought, and the nature of the DW gapping is not CDW. This discovery opens a parallel path to the study of the electron spin state and its possible connections to other unusual properties. PMID- 26853455 TI - Neuro-Interventions for the Neonates with Brain Arteriovenous Fistulas: With Special Reference to Access Routes. AB - Neonatal neuro-intervention is challenging. The purpose of this article is to report the neuro-intervention for the neonates with brain arteriovenous fistulas (AVFs), with special reference to access routes. Fifteen neonates (12 boys and 3 girls) who underwent neuro-intervention within the first 14 days of life were included. Their diagnoses included vein of Galen aneurysmal malformation (6), dural sinus malformations with arteriovenous (AV) shunts (6), pial AVF (2), and epidural AVF (1). Birth weight ranged from 1,538 g to 3,778 g (mean 2,525 g). Neuro-interventions, especially access routes, in the neonatal periods (< 1 month) were retrospectively reviewed. All neonates presented with severe cardiac failure. In total, 29 interventions (mean 1.9) were performed within 1 month. Although 12 neonates with birth weight more than 2,700 g could be treated through transfemoral arterial routes, 3 neonates with birth weight less than 2,200 g could not be treated successfully by femoral arterial routes. Interventions were performed through 19 femoral arterial, 3 femoral venous, 2 umbilical arterial, 3 umbilical venous, 3 transcardiac, and 2 direct carotid routes. Their overall outcomes were six good recovery, one moderate disability, two severe disabilities, one vegetative state, and five deaths with a mean follow-up period of 7 years 2 months. Neuro-intervention for the neonates with birth weight more than 2,700 g can be performed by femoral arterial routes using a 4F sheath. For those with birth weight less than 2,200 g, however, alternative access routes are required. PMID- 26853456 TI - Production of Human papillomavirus pseudovirions in plants and their use in pseudovirion-based neutralisation assays in mammalian cells. AB - Human papillomaviruses (HPV) cause cervical cancer and have recently also been implicated in mouth, laryngeal and anogenital cancers. There are three commercially available prophylactic vaccines that show good efficacy; however, efforts to develop second-generation vaccines that are more affordable, stable and elicit a wider spectrum of cross-neutralising immunity are still ongoing. Testing antisera elicited by current and candidate HPV vaccines for neutralizing antibodies is done using a HPV pseudovirion (PsV)-based neutralisation assay (PBNA). PsVs are produced by transfection of mammalian cell cultures with plasmids expressing L1 and L2 capsid proteins, and a reporter gene plasmid, a highly expensive process. We investigated making HPV-16 PsVs in plants, in order to develop a cheaper alternative. The secreted embryonic alkaline phosphatase (SEAP) reporter gene and promoter were cloned into a geminivirus-derived plant expression vector, in order to produce circular dsDNA replicons. This was co introduced into Nicotiana benthamiana plants with vectors expressing L1 and L2 via agroinfiltration, and presumptive PsVs were purified. The PsVs contained DNA, and could be successfully used for PBNA with anti-HPV antibodies. This is the first demonstration of the production of mammalian pseudovirions in plants, and the first demonstration of the potential of plants to make DNA vaccines. PMID- 26853458 TI - Muscle activity patterns and spinal shrinkage in office workers using a sit-stand workstation versus a sit workstation. AB - Reducing sitting time by means of sit-stand workstations is an emerging trend, but further evidence is needed regarding their health benefits. This cross sectional study compared work time muscle activity patterns and spinal shrinkage between office workers (aged 24-62, 58.3% female) who used either a sit-stand workstation (Sit-Stand group, n = 10) or a traditional sit workstation (Sit group, n = 14) for at least the past three months. During one typical workday, muscle inactivity and activity from quadriceps and hamstrings were monitored using electromyography shorts, and spinal shrinkage was measured using stadiometry before and after the workday. Compared with the Sit group, the Sit Stand group had less muscle inactivity time (66.2 +/- 17.1% vs. 80.9 +/- 6.4%, p = 0.014) and more light muscle activity time (26.1 +/- 12.3% vs. 14.9 +/- 6.3%, p = 0.019) with no significant difference in spinal shrinkage (5.62 +/- 2.75 mm vs. 6.11 +/- 2.44 mm). This study provides evidence that working with sit-stand workstations can promote more light muscle activity time and less inactivity without negative effects on spinal shrinkage. Practitioner Summary: This cross sectional study compared the effects of using a sit-stand workstation to a sit workstation on muscle activity patterns and spinal shrinkage in office workers. It provides evidence that working with a sit-stand workstation can promote more light muscle activity time and less inactivity without negative effects on spinal shrinkage. PMID- 26853457 TI - Using shared needles for subcutaneous inoculation can transmit bluetongue virus mechanically between ruminant hosts. AB - Bluetongue virus (BTV) is an economically important arbovirus of ruminants that is transmitted by Culicoides spp. biting midges. BTV infection of ruminants results in a high viraemia, suggesting that repeated sharing of needles between animals could result in its iatrogenic transmission. Studies defining the risk of iatrogenic transmission of blood-borne pathogens by less invasive routes, such as subcutaneous or intradermal inoculations are rare, even though the sharing of needles is common practice for these inoculation routes in the veterinary sector. Here we demonstrate that BTV can be transmitted by needle sharing during subcutaneous inoculation, despite the absence of visible blood contamination of the needles. The incubation period, measured from sharing of needles, to detection of BTV in the recipient sheep or cattle, was substantially longer than has previously been reported after experimental infection of ruminants by either direct inoculation of virus, or through blood feeding by infected Culicoides. Although such mechanical transmission is most likely rare under field condition, these results are likely to influence future advice given in relation to sharing needles during veterinary vaccination campaigns and will also be of interest for the public health sector considering the risk of pathogen transmission during subcutaneous inoculations with re-used needles. PMID- 26853459 TI - Sustainability of Transient Kinetic Regimes and Origins of Death. AB - It is generally recognized that a distinguishing feature of life is its peculiar capability to avoid equilibration. The origin of this capability and its evolution along the timeline of abiogenesis is not yet understood. We propose to study an analog of this phenomenon that could emerge in non-biological systems. To this end, we introduce the concept of sustainability of transient kinetic regimes. This concept is illustrated via investigation of cooperative effects in an extended system of compartmentalized chemical oscillators under batch and semi batch conditions. The computational study of a model system shows robust enhancement of lifetimes of the decaying oscillations which translates into the evolution of the survival function of the transient non-equilibrium regime. This model does not rely on any form of replication. Rather, it explores the role of a structured effective environment as a contributor to the system-bath interactions that define non-equilibrium regimes. We implicate the noise produced by the effective environment of a compartmentalized oscillator as the cause of the lifetime extension. PMID- 26853460 TI - Shaping metallic glasses by electromagnetic pulsing. AB - With damage tolerance rivalling advanced engineering alloys and thermoplastic forming capabilities analogous to conventional plastics, metallic glasses are emerging as a modern engineering material. Here, we take advantage of their unique electrical and rheological properties along with the classic Lorentz force concept to demonstrate that electromagnetic coupling of electric current and a magnetic field can thermoplastically shape a metallic glass without conventional heating sources or applied mechanical forces. Specifically, we identify a process window where application of an electric current pulse in the presence of a normally directed magnetic field can ohmically heat a metallic glass to a softened state, while simultaneously inducing a large enough magnetic body force to plastically shape it. The heating and shaping is performed on millisecond timescales, effectively bypassing crystallization producing fully amorphous shaped parts. This electromagnetic forming approach lays the groundwork for a versatile, time- and energy-efficient manufacturing platform for ultrastrong metals. PMID- 26853462 TI - Acute vestibulocochlear neuritis following postexposure rabies prophylaxis. PMID- 26853461 TI - Longitudinal Prediction of the Infant Gut Microbiome with Dynamic Bayesian Networks. AB - Sequencing of the 16S rRNA gene allows comprehensive assessment of bacterial community composition from human body sites. Previously published and publicly accessible data on 58 preterm infants in the Neonatal Intensive Care Unit who underwent frequent stool collection was used. We constructed Dynamic Bayesian Networks from the data and analyzed predictive performance and network characteristics. We constructed a DBN model of the infant gut microbial ecosystem, which explicitly captured specific relationships and general trends in the data: increasing amounts of Clostridia, residual amounts of Bacilli, and increasing amounts of Gammaproteobacteria that then give way to Clostridia. Prediction performance of DBNs with fewer edges were overall more accurate, although less so on harder-to-predict subjects (p = 0.045). DBNs provided quantitative likelihood estimates for rare abruptions events. Iterative prediction was less accurate (p < 0.001), but showed remarkable insensitivity to initial conditions and predicted convergence to a mix of Clostridia, Gammaproteobacteria, and Bacilli. DBNs were able to identify important relationships between microbiome taxa and predict future changes in microbiome composition from measured or synthetic initial conditions. DBNs also provided likelihood estimates for sudden, dramatic shifts in microbiome composition, which may be useful in guiding further analysis of those samples. PMID- 26853463 TI - Responses of Nigella sativa L. to Zinc Excess: Focus on Germination, Growth, Yield and Yield Components, Lipid and Terpene Metabolism, and Total Phenolics and Antioxidant Activities. AB - A comprehensive analysis of the responses of Nigella sativa L. to elevated zinc concentrations was assessed in pot experiments. Zn excess supply did not affect the germination but drastically reduced radicle elongation. A concentration dependent reduction in all growth parameters, yield, and yield components was observed. With the increasing Zn concentrations, total lipid contents decreased and changes in fatty composition toward the production of saturated ones were underscored. Despite the reduction in the seeds essential oil yield, a redirection of the terpene metabolism toward the synthesis of oxygenated compounds has been evidenced. A significant increase in the total phenols and flavonoids contents concomitant with improved antioxidant activities has also been found. Collectively, these results highlight the possible use of N. sativa L. in phytoremediation applications, on the one hand, and that Zn excess could represent an excellent alternative to improve the nutritional attributes of this important species, on the other hand. PMID- 26853464 TI - Ceramide Synthase 5 Is Essential to Maintain C16:0-Ceramide Pools and Contributes to the Development of Diet-induced Obesity. AB - Ceramides are bioactive sphingolipids, which are composed of sphingoid bases carrying acyl chains of various lengths. Ceramides are synthesized by a family of six ceramide synthases (CerS) in mammals, which produce ceramides with differentN linked acyl chains. Increased ceramide levels are known to contribute to the development of obesity and insulin resistance. Recently, it has been demonstrated that the ceramide acylation pattern is of particular importance for an organism to maintain energy homeostasis. However, which of theCerSfamily members are involved in this process is not yet completely known. Using newly developedCerS5knock-out mice, we show here thatCerS5is essential to maintain cellular C16:0sphingolipid pools in lung, spleen, muscle, liver, and white adipose tissue. Glycerophospholipid levels inCerS5-deficient mice were not altered. We found a strong impact of CerS5-dependent ceramide synthesis in white adipose tissue after high fat diet feeding. In skeletal muscle, liver, and spleen, C16:0-ceramide levels were altered independent of feeding conditions. The loss ofCerS5is associated with reduced weight gain and improved systemic health, including maintenance of glucose homeostasis and reduced white adipose tissue inflammation after high fat diet challenge. Our findings indicate that reduction of endogenous C16:0-ceramide by genetic inhibition ofCerS5is sufficient to ameliorate obesity and its comorbidities. PMID- 26853465 TI - Inhibition of cholesterol metabolism underlies synergy between mTOR pathway inhibition and chloroquine in bladder cancer cells. AB - Mutations to fibroblast growth factor receptor 3 (FGFR3) and phosphatase and tensin homologue (PTEN) signalling pathway components (for example, PTEN loss, PIK3CA, AKT1, TSC1/2) are common in bladder cancer, yet small-molecule inhibitors of these nodes (FGFR/PTENi) show only modest activity in preclinical models. As activation of autophagy is proposed to promote survival under FGFR/PTENi, we have investigated this relationship in a panel of 18 genetically diverse bladder cell lines. We found that autophagy inhibition does not sensitise bladder cell lines to FGFR/PTENi, but newly identify an autophagy-independent cell death synergy in FGFR3-mutant cell lines between mTOR (mammalian target of rapamycin) pathway inhibitors and chloroquine (CQ)-an anti-malarial drug used as a cancer therapy adjuvant in over 30 clinical trials. The mechanism of synergy is consistent with lysosomal cell death (LCD), including cathepsin-driven caspase activation, and correlates with suppression of cSREBP1 and cholesterol biosynthesis in sensitive cell lines. Remarkably, loss of viability can be rescued by saturating cellular membranes with cholesterol or recapitulated by statin-mediated inhibition, or small interfering RNA knockdown, of enzymes regulating cholesterol metabolism. Modulation of CQ-induced cell death by atorvastatin and cholesterol is reproduced across numerous cell lines, confirming a novel and fundamental role for cholesterol biosynthesis in regulating LCD. Thus, we have catalogued the molecular events underlying cell death induced by CQ in combination with an anticancer therapeutic. Moreover, by revealing a hitherto unknown aspect of lysosomal biology under stress, we propose that suppression of cholesterol metabolism in cancer cells should elicit synergy with CQ and define a novel approach to future cancer treatments. PMID- 26853467 TI - Novel strategy for a bispecific antibody: induction of dual target internalization and degradation. AB - Activation of the extensive cross-talk among the receptor tyrosine kinases (RTKs), particularly ErbB family-Met cross-talk, has emerged as a likely source of drug resistance. Notwithstanding brilliant successes were attained while using small-molecule inhibitors or antibody therapeutics against specific RTKs in multiple cancers over recent decades, a high recurrence rate remains unsolved in patients treated with these targeted inhibitors. It is well aligned with multifaceted properties of cancer and cross-talk and convergence of signaling pathways of RTKs. Thereby many therapeutic interventions have been actively developed to overcome inherent or acquired resistance. To date, no bispecific antibody (BsAb) showed complete depletion of dual RTKs from the plasma membrane and efficient dual degradation. In this manuscript, we report the first findings of a target-specific dual internalization and degradation of membrane RTKs induced by designed BsAbs based on the internalizing monoclonal antibodies and the therapeutic values of these BsAbs. Leveraging the anti-Met mAb able to internalize and degrade by a unique mechanism, we generated the BsAbs for Met/epidermal growth factor receptor (EGFR) and Met/HER2 to induce an efficient EGFR or HER2 internalization and degradation in the presence of Met that is frequently overexpressed in the invasive tumors and involved in the resistance against EGFR- or HER2-targeted therapies. We found that Met/EGFR BsAb ME22S induces dissociation of the Met-EGFR complex from Hsp90, followed by significant degradation of Met and EGFR. By employing patient-derived tumor models we demonstrate therapeutic potential of the BsAb-mediated dual degradation in various cancers. PMID- 26853466 TI - HDAC7 inhibition resets STAT3 tumorigenic activity in human glioblastoma independently of EGFR and PTEN: new opportunities for selected targeted therapies. AB - To date, the mutational status of EGFR and PTEN has been shown as relevant for favoring pro- or anti-tumor functions of STAT3 in human glioblastoma multiforme (GBM). We have screened genomic data from 154 patients and have identified a strong positive correlation between STAT3 and HDAC7 expression. In the current work we show the existence of a subpopulation of patients overexpressing HDAC7 and STAT3 that has particularly poor clinical outcome. Surprisingly, the somatic mutation rate of both STAT3 and HDAC7 was insignificant in GBM comparing with EGFR, PTEN or TP53. Depletion of HDAC7 in a range of GBM cells induced the expression of tyrosine kinase JAK1 and the tumor suppressor AKAP12. Both proteins synergistically sustained the activity of STAT3 by inducing its phosphorylation (JAK1) and protein expression (AKAP12). In absence of HDAC7, activated STAT3 was responsible for significant imbalance of secreted pro-/anti-angiogenic factors. This inhibited the migration and sprouting of endothelial cells in paracrine fashion in vitro as well as angiogenesis in vivo. In a murine model of GBM, induced HDAC7-silencing decreased the tumor burden by threefold. The current data show for the first time that silencing HDAC7 can reset the tumor suppressor activity of STAT3, independently of the EGFR/PTEN/TP53 background of the GBM. This effect could be exploited to overcome tumor heterogeneity and provide a new rationale behind the development of specific HDAC7 inhibitors for clinical use. PMID- 26853470 TI - [Innovation in Surgery]. PMID- 26853468 TI - Inhibition of colon cancer growth by docosahexaenoic acid involves autocrine production of TNFalpha. AB - The omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has anti inflammatory and anti-cancer properties. Among pro-inflammatory mediators, tumor necrosis factor alpha (TNFalpha) plays a paradoxical role in cancer biology with induction of cancer cell death or survival depending on the cellular context. The objective of the study was to evaluate the role of TNFalpha in DHA-mediated tumor growth inhibition and colon cancer cell death. The treatment of human colorectal cancer cells, HCT-116 and HCT-8 cells, with DHA triggered apoptosis in autocrine TNFalpha-dependent manner. We demonstrated that DHA-induced increased content of TNFalpha mRNA occurred through a post-transcriptional regulation via the down regulation of microRNA-21 (miR-21) expression. Treatment with DHA led to nuclear accumulation of Foxo3a that bounds to the miR-21 promoter triggering its transcriptional repression. Moreover, inhibition of RIP1 kinase and AMP-activated protein kinase alpha reduced Foxo3a nuclear-cytoplasmic shuttling and subsequent increase of TNFalpha expression through a decrease of miR-21 expression in DHA treated colon cancer cells. Finally, we were able to show in HCT-116 xenograft tumor-bearing nude mice that a DHA-enriched diet induced a decrease of human miR 21 expression and an increase of human TNFalpha mRNA expression limiting tumor growth in a cancer cell-derived TNFalpha dependent manner. Altogether, the present work highlights a novel mechanism for anti-cancer action of DHA involving colon cancer cell death mediated through autocrine action of TNFalpha. PMID- 26853469 TI - A RelA(p65) Thr505 phospho-site mutation reveals an important mechanism regulating NF-kappaB-dependent liver regeneration and cancer. AB - Post-translational modifications of nuclear factor (NF)-kappaB subunits provide a mechanism to differentially regulate their activity in response to the many stimuli that induce this pathway. However, the physiological significance of these modifications is largely unknown, and it remains unclear if these have a critical role in the normal and pathological functions of NF-kappaB in vivo. Among these, phosphorylation of the RelA(p65) Thr505 residue has been described as an important regulator of NF-kappaB activity in cell lines, but its physiological significance was not known. Therefore, to learn more about the role of this pathway in vivo, we generated a knockin mouse with a RelA T505A mutation. Unlike RelA knockout mice, the RelA T505A mice develop normally but exhibit aberrant hepatocyte proliferation following liver partial hepatectomy or damage resulting from carbon tetrachloride (CCl4) treatment. Consistent with these effects, RelA T505A mice exhibit earlier onset of cancer in the N nitrosodiethylamine model of hepatocellular carcinoma. These data reveal a critical pathway controlling NF-kappaB function in the liver that acts to suppress the tumour-promoting activities of RelA. PMID- 26853471 TI - Synthesis of Pyrido-Fused Quinazolinone Derivatives via Copper-Catalyzed Domino Reaction. AB - A simple and efficient synthesis of 11H-pyrido[2,1-b]quinazolin-11-ones by Cu(OAc)2.H2O-catalyzed reaction of easily available substituted isatins and 2 bromopyridine derivatives has been developed. The reaction involves C-N/C-C bond cleavage and two C-N bond formations in a one-pot operation. This methodology is complementary to previously reported synthetic procedures, and two plausible reaction mechanisms are discussed. PMID- 26853472 TI - Dynein Clusters into Lipid Microdomains on Phagosomes to Drive Rapid Transport toward Lysosomes. AB - Diverse cellular processes are driven by motor proteins that are recruited to and generate force on lipid membranes. Surprisingly little is known about how membranes control the force from motors and how this may impact specific cellular functions. Here, we show that dynein motors physically cluster into microdomains on the membrane of a phagosome as it matures inside cells. Such geometrical reorganization allows many dyneins within a cluster to generate cooperative force on a single microtubule. This results in rapid directed transport of the phagosome toward microtubule minus ends, likely promoting phagolysosome fusion and pathogen degradation. We show that lipophosphoglycan, the major molecule implicated in immune evasion of Leishmania donovani, inhibits phagosome motion by disrupting the clustering and therefore the cooperative force generation of dynein. These findings appear relevant to several pathogens that prevent phagosome-lysosome fusion by targeting lipid microdomains on phagosomes. PMID- 26853473 TI - Metabolic Heterogeneity in Human Lung Tumors. AB - Non-small cell lung cancer (NSCLC) is heterogeneous in the genetic and environmental parameters that influence cell metabolism in culture. Here, we assessed the impact of these factors on human NSCLC metabolism in vivo using intraoperative (13)C-glucose infusions in nine NSCLC patients to compare metabolism between tumors and benign lung. While enhanced glycolysis and glucose oxidation were common among these tumors, we observed evidence for oxidation of multiple nutrients in each of them, including lactate as a potential carbon source. Moreover, metabolically heterogeneous regions were identified within and between tumors, and surprisingly, our data suggested potential contributions of non-glucose nutrients in well-perfused tumor areas. Our findings not only demonstrate the heterogeneity in tumor metabolism in vivo but also highlight the strong influence of the microenvironment on this feature. PMID- 26853475 TI - The client-centred approach as experienced by male neurological rehabilitation clients in occupational therapy. A qualitative study based on a grounded theory tradition. AB - Purpose To explore the perspectives of male clients in a neurological rehabilitation setting with regard to the occupational therapy they have received and the client-centred approach. Method This study involved a qualitative research design based on the grounded theory tradition. Individual in-depth interviews were used to collect data. Data were analysed using a constant comparative method. Seven male participants from an inpatient neurological setting were included using a theoretical sampling technique. Results Three themes emerged to describe the approach of the therapists to client-centred practice: (a) a shared biomedical focus as the start of the rehabilitation process, (b) the un-simultaneous shift from a biomedical towards a psycho-social focus and (c) formal versus informal nature of gathering client information. Conclusion A client-centred approach entails a shift from the therapist focussing on recovery from the short-term neurological issues towards the long-term consequences of the disease. According to the client, this shift in reasoning must occur at a specific and highly subjective moment during the rehabilitation process. Identifying this moment could strengthen the client-centred approach. Implications for Rehabilitation Client-centred practice entails a shift from recovering the short-term neurological issues towards the long-term psycho-social consequences of the disease. To be effective in client-centred practice, the clients expect from the professional to be an authority with regard to biomedical issues and to be partner with regard to psycho-social issues. Client-centred practice is most likely to be successful when client is susceptible to discuss his psycho-social issues and finding this moment is a challenge for the professional. Using formal methods for goal setting do not necessarily cover all the information needed for a client-centred therapy programme. Rather, using informal methods could lead to a more valid image of the client. PMID- 26853474 TI - Degradation of Phage Transcripts by CRISPR-Associated RNases Enables Type III CRISPR-Cas Immunity. AB - Type III-A CRISPR-Cas systems defend prokaryotes against viral infection using CRISPR RNA (crRNA)-guided nucleases that perform co-transcriptional cleavage of the viral target DNA and its transcripts. Whereas DNA cleavage is essential for immunity, the function of RNA targeting is unknown. Here, we show that transcription-dependent targeting results in a sharp increase of viral genomes in the host cell when the target is located in a late-expressed phage gene. In this targeting condition, mutations in the active sites of the type III-A RNases Csm3 and Csm6 lead to the accumulation of the target phage mRNA and abrogate immunity. Csm6 is also required to provide defense in the presence of mutated phage targets, when DNA cleavage efficiency is reduced. Our results show that the degradation of phage transcripts by CRISPR-associated RNases ensures robust immunity in situations that lead to a slow clearance of the target DNA. PMID- 26853476 TI - Complete genome sequence of a xanthan-degrading Microbacterium sp. strain XT11 with the potential for xantho-oligosaccharides production. AB - Here, we reported a high-quality complete genome sequence of a xanthan-degrading bacterium Microbacterium sp. XT11, newly isolated from garden soil, China. Several genes probably involved in xanthan degradation pathway were detected as a gene cluster in the genome. The genome information of strain XT11 will be valuable for clarifying the molecular mechanism for xanthan degradation and producing xantho-oligosaccharides. PMID- 26853477 TI - Alkane biohydroxylation: Interests, constraints and future developments. AB - Alkanes constitute one of the vastest reserves of raw materials for the production of fine chemicals. This paper focuses on recent advances in alkane biohydroxylation, i.e. the bioactivation of alkanes into their corresponding alcohols. Enzyme and whole-cell biocatalysts have been reviewed. Process considerations to implement such biocatalysts in bioreactors at large scale by coupling the bioconversion with cofactor regeneration and product removal are also discussed. PMID- 26853478 TI - Complete genome sequence of the bioleaching bacterium Leptospirillum sp. group II strain CF-1. AB - We describe the complete genome sequence of Leptospirillum sp. group II strain CF 1, an acidophilic bioleaching bacterium isolated from an acid mine drainage (AMD). This work provides data to gain insights about adaptive response of Leptospirillum spp. to the extreme conditions of bioleaching environments. PMID- 26853479 TI - Complete genome sequence of Lactobacillus paraplantarum L-ZS9, a probiotic starter producing class II bacteriocins. AB - Lactobacillus paraplantarum L-ZS9 is a probiotic starter isolated from fermented sausage and it is a great producer of class II bacteriocins. To the best of our knowledge, this is the first complete sequenced genome of L. paraplantarum deposited in GenBank database. The size of the complete genome of L. paraplantarum L-ZS9 is 3,139,729 bp. The genomic sequence revealed that this strain includes 19 genes involved in class II bacteriocins production and regulation. The information fill the gaps of the L. paraplantarum genome information and contribute to the improvement of class II bacteriocins research. PMID- 26853480 TI - Complete genome sequence of Streptomyces globisporus C-1027, the producer of an enediyne antibiotic lidamycin. AB - Streptomyces globisporus C-1027 produces a nine-membered enediyne antitumor antibiotic lidamycin. Here we report the complete genome sequence of S. globisporus C-1027, which consists of a 7,608,611 bp linear chromosome, a 167,754 bp linear plasmid SGLP1 and a 7,234 bp circular plasmid pSGL1. The biosynthetic gene cluster for lidamycin was located in the linear plasmid SGLP1. Genome analysis also revealed a number of genes related to biosynthesis of diverse secondary metabolites. The genome sequence of C-1027 will enable us to disclose biosynthetic pathways of these secondary metabolites and discover new natural products with potential applications notably in human health. PMID- 26853481 TI - Silent obstruction in a young woman with systemic lupus erythematosus: a case report and literature review on kidney injury from ureteral endometriosis. AB - INTRODUCTION: Endometriosis is the most common pelvic gynaecologic disorder affecting pre-menopausal women. However ureteral endometriosis (UE) especially intrinsic urinary tract endometriosis is a rare finding that is notorious for causing silent renal insult. The pathogenesis of endometriosis still remains a mystery but studies have suggested an association between endometriosis and systemic lupus erythematosus (SLE) suggesting an immunological aspect to endometriosis. There is very little recognition in the renal literature of the significance of UE leading to progressive kidney injury and the association with autoimmune conditions in particular SLE. CASE DESCRIPTION: We present a case of a 30-year old female with a background history of SLE with a silent progressive kidney injury due to an obstructive uropathy secondary to bilateral intrinsic UE and severe loss of her left kidney function that was treated with ureteric stenting. She subsequently underwent bilateral re-implantation of her ureters as a definitive treatment plan as she expressed a wish to conceive. DISCUSSION: Progressive kidney injury as a result of UE has been reported in the past, however its true incidence is not known. The time of diagnosis is crucial as it reflects renal prognosis. This article outlines the clinical implications from the renal perspective of the disease considering the relevant health problem UE can impose to women. This paper discusses the emerging evidence of an association between SLE and endometriosis that remains poorly understood. CONCLUSION: A high index of suspicion is required to diagnose UE as the disease occurs insidiously with non-specific symptoms leading to a silent obstructive uropathy. If missed it can ultimately lead to irreversible kidney dysfunction and mortality. We suggest that patients with endometriosis especially UE should be followed up regularly with renal function testing and imaging. Any health professionals dealing with patients suffering from SLE should consider appropriate investigations and referral if any symptom that suggests endometriosis is reported. PMID- 26853482 TI - [Endometriosis and ovarian cancer: An old story...]. PMID- 26853483 TI - Cardiac imaging evaluation is mandatory in patients with anorexia nervosa. PMID- 26853484 TI - Effects of long-term folate supplementation on metabolic status and regression of cervical intraepithelial neoplasia: A randomized, double-blind, placebo controlled trial. AB - OBJECTIVE: This study was conducted to determine the effects of long-term folate supplementation on regression and metabolic status of patients with cervical intraepithelial neoplasia grade 1 (CIN1). METHODS: This randomized, double-blind, placebo-controlled trial was performed among 58 women diagnosed with CIN1, ages 18 to 55 y old. Participants were randomly divided into two groups to receive 5 mg/d folate supplements (n = 29) or placebo (n = 29) for 6 mo. Fasting blood samples were taken at baseline and 6 mo after intervention to quantify related markers. RESULTS: A greater percentage of women in the folate group had regressed CIN1 (83.3 versus 52.0%, P = 0.019) than those in the placebo group. Long-term folate supplementation resulted in a significant decrease in serum insulin levels (-1.6 +/- 6.2 versus +2.6 +/- 6.9 MUIU/mL, P = 0.018) and homeostatic model assessment-beta cell function (HOMA-B) (-13.0 +/- 39.0 versus +11.2 +/- 42.3, P = 0.028) compared with the placebo. Additionally, plasma glutathione (GSH) levels were significantly increased (+81.5 +/- 264.1 versus -220.9 +/- 342.5 MUmol/L, P < 0.001) and malondialdehyde (MDA) levels were significantly reduced (-1.0 +/- 1.1 versus +0.1 +/- 1.6 MUmol/L, P = 0.004) in the folate group compared to the placebo. CONCLUSIONS: Taken together, folate supplementation (5 mg/d) for 6 mo among women with CIN1 resulted in its regression as well as led to decreased serum insulin, HOMA-B, plasma MDA and increased plasma GSH levels; however, it did not affect other metabolic profiles. PMID- 26853485 TI - Adrenal tuberculosis masquerading as disseminated malignancy: A pitfall of (18)F FDG PET/CT Imaging. AB - Non-invasive characterization of adrenal lesions is a commonly encountered diagnostic challenge. Characteristic clinical and correlative imaging findings may assist in only arriving at a probable diagnosis. Currently, (18)F-FDG PET/CT is considered to provide the most comprehensive imaging information. We here present a case of bilateral adrenal tuberculosis that highlights the need for caution during the interpretation of (18)F-FDG PET/CT and also the need to suggest histopathological correlation. PMID- 26853486 TI - Expression of two insulin receptor subtypes, insra and insrb, in zebrafish (Danio rerio) ovary and involvement of insulin action in ovarian function. AB - Present study reports differential expression of the two insulin receptor (IR) subtypes in zebrafish ovary at various stages of follicular growth and potential involvement of IR in insulin-induced oocyte maturation. The results showed that mRNA expression for IR subtypes, insra and insrb, exhibited higher levels in mid vitellogenic (MV) and full-grown (FG) rather than pre-vitellogenic (PV) oocytes. Interestingly, compared to the levels in denuded oocytes, mRNAs for both insra and insrb were expressed at much higher level in the follicle layer harvested from FG oocytes. Immunoprecipitation using IRbeta antibody could detect a protein band of desired size (~95kDa) in FG oocyte lysates. Further, IRbeta immunoreactivity was detected in ovarian tissue sections, especially at the follicle layer and oocyte membrane of MV and FG, but not PV stage oocytes. While hCG (10IU/ml) stimulation was without effect, priming with insulin (5MUM) could promote oocyte maturation of MV oocytes in a manner sensitive to de novo protein and steroid biosynthesis. Compared to hCG, in insulin pre-incubated MV oocytes, stimulation with maturation inducing steroid (MIS), 17alpha,20beta-dihydroxy-4 pregnen-3-one (DHP) elicited higher maturational response. Potential involvement of insulin-mediated action on acquisition of maturational competence and regulation of oocyte maturation was further manifested through up regulation of 20beta-hydroxysteroid dehydrogenase (20beta-hsd), MIS receptor (mPRalpha), insulin-like growth factor 3 (igf3) and IGF1 receptor (igf1rb), but not cyp19a expression in MV oocytes. Moreover, priming with anti-IRbeta attenuated insulin action on meiotic G2-M1 transition indicating the specificity of insulin action and physiological relevance of IR in zebrafish ovary. PMID- 26853487 TI - Leptin stimulates hepatic growth hormone receptor and insulin-like growth factor gene expression in a teleost fish, the hybrid striped bass. AB - Leptin is an anorexigenic peptide hormone that circulates as an indicator of adiposity in mammals, and functions to maintain energy homeostasis by balancing feeding and energy expenditure. In fish, leptin tends to be predominantly expressed in the liver, another important energy storing tissue, rather than in fat depots as it is in mammals. The liver also produces the majority of circulating insulin-like growth factors (IGFs), which comprise the mitogenic component of the growth hormone (GH)-IGF endocrine growth axis. Based on similar regulatory patterns of leptin and IGFs that we have documented in previous studies on hybrid striped bass (HSB: Morone saxatilis*Morone chrysops), and considering the co-localization of these peptides in the liver, we hypothesized that leptin might regulate the endocrine growth axis in a manner that helps coordinate somatic growth with energy availability. Using a HSB hepatocyte culture system to simulate autocrine or paracrine exposure that might occur within the liver, this study examines the potential for leptin to modulate metabolism and growth through regulation of IGF gene expression directly, or indirectly through the regulation of GH receptors (GHR), which mediate GH-induced IGF expression. First, we verified that GH (50nM) has a classical stimulatory effect on IGF-1 and additionally show it stimulates IGF-2 transcription in hepatocytes. Leptin (5 and/or 50nM) directly stimulated in vitro GHR2 gene expression within 8h of exposure, and both GHR1 and GHR2 as well as IGF-1 and IGF 2 gene expression after 24h. Cells were then co-incubated with submaximal concentrations of leptin and GH (25nM each) to test if they had a synergistic effect on IGF gene expression, possibly through increased GH sensitivity following GHR upregulation by leptin. In combination, however, the treatments only had an additive effect on stimulating IGF-1 mRNA despite their capacity to increase GHR mRNA abundance. This suggests that leptin's stimulatory effect on GHRs may be limited to enhancing transcription or mRNA stability rather than inducing full translation of functional receptors, at least within a 24-h time frame. Finally, leptin was injected IP (100ng/g and 1MUg/gBW) to test the in vivo regulation of hepatic IGF-1 and GHR1 gene expression. The 100ng/g BW leptin dose significantly upregulated in vivo IGF-1 mRNA levels relative to controls after 24h of fasting, but neither dosage was effective at regulating GHR1 gene expression. These studies suggest that stimulation of growth axis component transcripts by leptin may be an important mechanism for coordinating somatic growth with nutritional state in these and perhaps other fish or vertebrates, and represent the first evidence of leptin regulating GHRs in vertebrates. PMID- 26853488 TI - Salivary immunoglobulin free light chains: reference ranges and responses to exercise in young and older adults. AB - BACKGROUND: Free light chains (FLCs) have a range of biological functions and may act as a broad marker of immunesuppression and activation and inflammation. Measurement of salivary FLCs may provide practical advantages in a range of clinical populations. The aim of the present study was to develop normal reference ranges of FLCs in saliva and assess the effects of acute exercise on FLC levels in younger and older adults. METHODS: Saliva FLC concentrations and secretion rates were measuredin young (n = 88, aged 18-36) and older (n = 53, aged 60-80) adults. To assess FLC changes in response to acute exercise, young adults completed a constant work-rate cycling exercise trial at 60% VO2max (n = 18) or a 1 h cycling time trial (TT) (n = 10) and older adults completed an incremental submaximal treadmill walking exercise test to 75% HRmax (n = 53). Serum FLCs were measured at baseline and in response to exercise. RESULTS: Older adults demonstrated significantly higher levels of salivary FLC parameters compared with young adults. Median (5-95th percentile) concentrationswere 0.45 (0.004- 3.45) mg/L for kappa and 0.30 (0.08-1.54) mg/L for lambda in young adults; 3.91 (0.75-19.65) mg/L for kappa and 1.00 (0.02-4.50) mg/L for lambda in older ad ults. Overall median concentrations of salivary kappa and lambda FLCs were 10-fold and 20-fold lower than serum, respectively. Reductions in salivary FLC concentrations and secretion rates were observed immediately post- and at 1 h post exercise, but were only significant for the older cohort; FLCs began to recover between post and 1 h post-exercise. No changes in serum FLCs were observed in response to exercise. PMID- 26853489 TI - Aberrant levels of Wnt/beta-catenin pathway components in a rat model of endometriosis. AB - Endometriosis is a benign gynecological disease affecting approximately 10-15% of women of reproductive age and 25-50% of all infertile women. It is characterized by the presence of glands and/or endometrial stroma outside the uterine cavity. Angiogenesis is a crucial process for the development and maintenance of endometriotic lesions. The Wnt/beta-catenin pathway is a major promoter of angiogenesis in both physiological and pathological conditions. In the present study, we evaluated the expression of molecules related to the Wnt/beta-catenin pathway in a rat model of peritoneal endometriosis. mRNA analyses showed significantly increased expression of Wnt4 and Wnt7b and decreased expression of Gsk3beta and E-cadherin in endometriotic lesions. However, there were no differences in beta-catenin and Fzd2 mRNA expression. In addition, we observed a significant increase of nuclear beta-catenin in endometriotic lesions, a hallmark of Wnt/ beta-catenin pathway activation. Stromal beta-catenin staining was found in 45.4% of endometrial tissues and 77.8% of endometriotic lesions. beta-catenin nuclear localization was found in 18.2% of the endometrial tissues and 33.3% of endometriotic lesions. Finally, the expression of galectin-3, a regulator of this pathway, was increased in endometriosis. In summary, this pattern of Wnt/beta catenin components expression suggests an increased activity of this pathway in endometriosis. PMID- 26853490 TI - Extended Foster Care for Transition-Age Youth: An Opportunity for Pregnancy Prevention and Parenting Support. AB - PURPOSE: This analysis examined California county birth rate variations among girls in foster care. The objective was to generate data to assess potential intervention points tied to federal legislation extending foster care beyond age 18 years. METHODS: Child protection records for all adolescent girls in foster care at age 17 years between 2003 and 2007 (N = 20,222) were linked to vital birth records through 2011. The cumulative percentage of girls who had given birth by age 21 years was calculated by county and race/ethnicity. RESULTS: One in three (35.2%) adolescent girls in foster care had given birth at least once before age 21 years. Although significant birth rate variations emerged, even at the low end of the county range, more than one in four girls had given birth by age 21 years. CONCLUSIONS: Child welfare systems are now charged with coordinating transitional services for foster youth beyond age 18 years. Extended foster care provides new opportunities for pregnancy prevention work and targeted parenting support. PMID- 26853492 TI - A target responsive aptamer machine for label-free and sensitive non-enzymatic recycling amplification detection of ATP. AB - Based on a new target-triggered aptamer molecular machine, a label-free and non enzymatic target recycling amplification strategy for sensitive fluorescence detection of ATP in human serums is described. The presence of the target ATP together with the DNA fuel strand initiates the operation of the aptamer machine and leads to cyclic reuse of ATP and the release of many G-quadruplex sequences, which associate with a fluorescent dye to generate significantly amplified fluorescence signals to achieve sensitive detection of ATP. PMID- 26853491 TI - Investigation of suspected viral hepatitis outbreaks in North West India. AB - Hepatitis E (HEV) infection is diagnosed on the basis of serum anti-HEV IgM detection. In outbreaks, early diagnostic method is important for prompt control measures. This study compared 3 diagnostic methods in 60 serum samples collected in suspected HEV outbreaks. The suitability of saliva samples for antibody detection was also evaluated in 21 paired serum saliva samples. The anti-HEV IgM, HEV-Ag, and HEV-RNA were detected in serum samples of 52 (86.66%), 16 (26.66%), and 18 (30%) patients, respectively. The concordance between serum and saliva IgM was found to be 76.91%. The positivity of PCR and HEV-Ag detection was 100% within 1 week of illness which declined to 5-10% thereafter. The outbreak was attributed to HEV genotype 1, subtype 1a, and the clinical and environmental strains clustered together. HEV-antigen and RNA were an early diagnostic marker with 96.66% concordance. Saliva samples can be used as an alternative in outbreak setting. PMID- 26853493 TI - Physical activity, sleep quality, and self-reported fatigue across the adult lifespan. AB - Deteriorating sleep quality and increased fatigue are common complaints of old age, and poor sleep is associated with decreased quality of life and increased mortality rates. To date, little attention has been given to the potential effects of physical activity on sleep quality and fatigue in aging. The purpose of this study was to examine the relationships between activity, sleep and fatigue across the adult lifespan. Sixty community-dwelling adults were studied; 22 younger (21-29 years), 16 middle-aged (36-64 years), and 22 older (65-81 years). Physical activity was measured by accelerometer. Sleep quality was assessed using the Pittsburg Sleep Quality Index. Self-reported fatigue was evaluated with the Patient-Reported Outcomes Measurement Information System (PROMIS). Regression analysis revealed a positive relationship between activity and sleep quality in the older (r(2)=0.18, p=0.05), but not the younger (r(2) = 0.041, p = 0.35) or middle-aged (r(2) = 0.001, p = 0.93) groups. This association was mainly established by the relationship between moderate-vigorous activity and sleep quality (r(2)=0.37, p=0.003) in older adults. No association was observed between physical activity and self-reported fatigue in any of the groups (r(2) <= 0.14, p >= 0.15). However, an inverse relationship was found between sleep quality and fatigue in the older (r(2) = 0.29, p = 0.05), but not the younger or middle-aged (r(2) <= 0.13, p >= 0.10) groups. These results support the hypothesis that physical activity may be associated with sleep quality in older adults, and suggest that improved sleep may mitigate self-reported fatigue in older adults in a manner that is independent of activity. PMID- 26853495 TI - The first report on coagulation and phospholipase A2 activities of Persian Gulf lionfish, Pterois russelli, an Iranian venomous fish. AB - Pterois russelli is a venomous fish belonging to scorpionidae family. Regarding to high significance value for tracing potential therapeutic molecules and special agents from venomous marine creatures, the present study was aimed to characterization of the Persian Gulf lionfish venom. Proteolytic, phospholipase, hemolytic, coagulation, edematogenic and dermonecrotic activities were determined for extracted venom. The LD50 of P. russelli venom was determined by intravenous injection in white Balb/c mice. Phospholipase A2 activity was recorded at 20 MUg of total venom. Coagulation activity on human plasma was shown by Prothrombin Time (PT) and activated Partial Thromboplastin Time (APTT) assays and coagulation visualized after 7 and 14 s respectively for 60 MUg of crude venom. LD50 was calculated as 10.5 mg/kg. SDS-PAGE revealed the presence of major and minor protein bands between 6 and 205 kDa. Different amounts of crude venom ranged from 1.87 to 30 MUg showed proteolytic activity on casein. The highest edematic activity was detected at 20 MUg. Our findings showed that the edematic activity was dose dependent and persisted for 48 h after injection. The crude venom did not induce dermonecrotic activity on rabbit skin and showed no hemolytic activity on human, mouse and rabbit erythrocytes. This is the first report for phospholipase A2 and coagulation activity in venomous fish and venomous marine animals respectively. Proteolytic activity of P. russelli venom is in accordance with the other genara of scorpionidae family. According to venom activity on intrinsic and extrinsic coagulation pathways, lionfish venom would be contained an interesting pharmaceutical agent. This study is pending to further characterization of phospholipase A2, coagulation, and protease activities and also in vivo activity on animal model of surface and internal bleeding. PMID- 26853494 TI - Genome-wide analysis of abdominal and pleural malignant mesothelioma with DNA arrays reveals both common and distinct regions of copy number alteration. AB - Malignant mesothelioma (MM) is an aggressive tumor arising from mesothelial linings of the serosal cavities. Pleural space is the most common site, accounting for about 80% of cases, while peritoneum makes up the majority of the remaining 20%. While histologically similar, tumors from these sites are epidemiologically and clinically distinct and their attribution to asbestos exposure differs. We compared DNA array-based findings from 48 epithelioid peritoneal MMs and 41 epithelioid pleural MMs to identify similarities and differences in copy number alterations (CNAs). Losses in 3p (BAP1 gene), 9p (CDKN2A) and 22q (NF2) were seen in tumors from both tumor sites, although CDKN2A and NF2 losses were seen at a higher rate in pleural disease (p<0.01). Overall, regions of copy number gain were more common in peritoneal MM, whereas losses were more common in pleural MM, with regions of loss containing known tumor suppressor genes and regions of gain encompassing genes encoding receptor tyrosine kinase pathway members. Cases with known asbestos causation (n = 32 ) were compared with those linked to radiation exposure (n = 9 ). Deletions in 6q, 14q, 17p and 22q, and gain of 17q were seen in asbestos-associated but not radiation-related cases. As reported in post-radiation sarcoma, gains outnumbered losses in radiation-associated MM. The patterns of genomic imbalances suggest overlapping and distinct molecular pathways in MM of the pleura and peritoneum, and that differences in causation (i.e., asbestos vs. radiation) may account for some of these site-dependent differences. PMID- 26853496 TI - Deciphering the main venom components of the ectoparasitic ant-like bethylid wasp, Scleroderma guani. AB - Similar to venom found in most venomous animals, parasitoid venoms contain a complex cocktail of proteins with potential agrichemical and pharmaceutical use. Even though parasitoids are one of the largest group of venomous animals, little is known about their venom composition. Recent few studies revealed high variated venom composition existing not only in different species but also between closely related strains, impling that increasing information on the venom proteins from more greater diversity of species of different taxa is key to comprehensively uncover the complete picture of parasitoid venom. Here, we explored the major protein components of the venom of ectoparasitic ant-like bethylid wasp, Scleroderma guani by an integrative transcriptomic-proteomic approach. Illumina deep sequencing of venom apparatus cDNA produced 49,873 transcripts. By mapping the peptide spectral data derived from venom reservoir against these transcripts, mass spectrometry analysis revealed ten main venom proteins, including serine proteinase, metalloprotease, dipeptidyl peptidase IV, esterase, antithrombin-III, acid phosphatase, neural/ectodermal development factor IMP-L2 like protein, venom allergen 3, and unknown protein. Interestingly, one serine proteinase was firstly identified with rarely high molecular weight about 200 kDa in parasitoid venom. The occurrence of abundant acid phosphatase, antithrombin-III and venom allergen 3 demonstrated that S. guani venom composition is similar to that of social wasp venoms. All identified venom genes showed abundantly biased expression in venom apparatus, indicating their virulent functions involved in parasitization. This study shed light on the more better understanding of parasitoid venom evolution across species and will facilitate the further elucidation of function and toxicity of these venom proteins. PMID- 26853497 TI - Homework Adherence and Cognitive Behaviour Treatment Outcome for Children and Adolescents with Anxiety Disorders. AB - BACKGROUND: Homework assignments are considered an essential component for a successful outcome of cognitive behavioural therapy for youths with anxiety disorders. However, only two studies have examined the association between homework adherence and outcome of cognitive behavioural therapy for youths with anxiety disorders. AIMS: The study examined the association between homework adherence and treatment outcome following a generic group cognitive behaviour treatment program (Cool Kids) for anxiety disordered youths and their parents. METHOD: The treatment program was completed by 98 children and adolescents (ages 7-16). Homework adherence was measured as time spent doing homework assignments between each session, reported by youths as well as parents. Outcome criteria consisted of youth-reported anxiety symptoms and clinician rated severity of primary anxiety diagnosis at posttreatment and 3-month follow-up. RESULTS: Results did not support an association between homework adherence and treatment outcome when controlling for pretreatment severity. CONCLUSIONS: The study found no convincing evidence that homework adherence predicted outcome of cognitive behavioural therapy for youths with anxiety disorders. Reasons for divergent findings on homework adherence in cognitive behavioural therapy for youths compared to adults are discussed. PMID- 26853498 TI - Internal structure of sponge glass fiber revealed by ptychographic nanotomography. AB - Sponge glass spicules have solicited great interest due to their mechanical and optical properties. Herein we use ptychographic nanotomography to obtain detailed insights into the internal structure of an anchor spicule from the Venus flower basket. The obtained dataset has 90nm resolution in 3D and provides quantitative determination of the electron density. The data reveal significant variations in electron density across the spicule. The central organic filament is found to be slightly but significantly displaced from the spicule central axis. Analysis of the electron density affords an estimate of a protein volume fraction in the organic filament of about 70%. In the highly mineralized part of the spicule, the electron density is seen to display circular symmetry and be neigh independent of position along the spicule long axis. Variations in the electron density beyond those included in current models of spicule mechanics are observed. PMID- 26853500 TI - Identification of phosphorus deficiency responsive proteins in a high phosphorus acquisition soybean (Glycine max) cultivar through proteomic analysis. AB - As one of the major oil crops, soybean might be seriously affected by phosphorus deficiency on both yield and quality. Understanding the molecular basis of phosphorus uptake and utilization in soybean may help to develop phosphorus (P) efficient cultivars. On this purpose, we conducted a comparative proteomic analysis on a high P acquisition soybean cultivar BX10 under low and high P conditions. A total of 61 unique proteins were identified as putative P deficiency responsive proteins. These proteins were involved in carbohydrate metabolism, protein biosynthesis/processing, energy metabolism, cellular processes, environmental defense/interaction, nucleotide metabolism, signal transduction, secondary metabolism and other metabolism related processes. Several proteins involved in energy metabolism, cellular processes, and protein biosynthesis and processing were found to be up-regulated in both shoots and roots, whereas, proteins involved in carbohydrate metabolism appeared to be down regulated. These proteins are potential candidates for improving P acquisition. These findings provide a useful starting point for further research that will provide a more comprehensive understanding of molecular mechanisms through which soybeans adapt to P deficiency condition. PMID- 26853499 TI - Response surface modeling for the inactivation of Bacillus subtilis subsp. niger spores by chlorine dioxide gas in an enclosed space. AB - Bacillus subtilis subsp. niger spores are a commonly used biological indicator to evaluate the disinfection of an enclosed space. In the present study, chlorine dioxide (ClO2) gas was applied to inactivate B. subtilis subsp. niger spores in an enclosed space. The effects of the ClO2 gas concentration (1-3 mg/l), relative humidity (RH, 30-70%) and exposure time (30-90 min) were investigated using a response surface methodology (RSM). A three-factor Box-Behnken experimental design was used. The obtained data were adequately fitted to a second-order polynomial model with an R2adj of 0.992. The ClO2 gas concentration, RH and exposure time all significantly (P<0.05) and positively correlated with the inactivation of B. subtilis subsp. niger spores. The interaction between the ClO2 gas concentration and RH as well as that between the exposure time and RH indicated significant and synergistic effects (P<0.05). The predictive model was validated by additional eight experiments and proven to be with good accuracy. Overall, this model established by the RSM could show the trend of the inactivation of spores, indicate the interactions between important factors, and provide a reference to determine effective conditions for the disinfection in different enclosed spaces by ClO2 gas. IMPLICATIONS: The inactivation of indoor biological contaminants plays an important role in preventing the transmission of pathogens and ensuring human safety. The predictive model using response surface methodology indicates the influence and interaction of the main factors on the inactivation of Bacillus subtilis subsp. niger spores by ClO2 gas, and can predict a ClO2 gas treatment condition to achieve an effective sterilization of enclosed spaces. The results in this paper will provide a reference for the application of ClO2 gas treatments for indoor disinfection. PMID- 26853501 TI - Imaging-Guided Core-Needle Breast Biopsy: Impact of Meditation and Music Interventions on Patient Anxiety, Pain, and Fatigue. AB - PURPOSE: To evaluate the impact of guided meditation and music interventions on patient anxiety, pain, and fatigue during imaging-guided breast biopsy. METHODS: After giving informed consent, 121 women needing percutaneous imaging-guided breast biopsy were randomized into three groups: (1) guided meditation; (2) music; (3) standard-care control group. During biopsy, the meditation and music groups listened to an audio-recorded, guided, loving-kindness meditation and relaxing music, respectively; the standard-care control group received supportive dialogue from the biopsy team. Immediately before and after biopsy, participants completed questionnaires measuring anxiety (State-Trait Anxiety Inventory Scale), biopsy pain (Brief Pain Inventory), and fatigue (modified Functional Assessment of Chronic Illness Therapy-Fatigue). After biopsy, participants completed questionnaires assessing radiologist-patient communication (modified Questionnaire on the Quality of Physician-Patient Interaction), demographics, and medical history. RESULTS: The meditation and music groups reported significantly greater anxiety reduction (P values < .05) and reduced fatigue after biopsy than the standard-care control group; the standard-care control group reported increased fatigue after biopsy. The meditation group additionally showed significantly lower pain during biopsy, compared with the music group (P = .03). No significant difference in patient-perceived quality of radiologist-patient communication was noted among groups. CONCLUSIONS: Listening to guided meditation significantly lowered biopsy pain during imaging-guided breast biopsy; meditation and music reduced patient anxiety and fatigue without compromising radiologist patient communication. These simple, inexpensive interventions could improve women's experiences during core-needle breast biopsy. PMID- 26853502 TI - Nurses' experiences of caring for the suddenly bereaved in adult acute and critical care settings, and the provision of person-centred care: A qualitative study. AB - AIM: To explore nursing interventions for person-centred bereavement care in adult acute and critical care settings. DESIGN: A descriptive exploratory study, involving focused, face-to-face interviews. Participants comprised nine registered nurses and one auxiliary nurse, working in environments where sudden death was known to occur, i.e. emergency, cardiac and critical care. Interviews were transcribed verbatim and data subjected to directed content analysis. The provision of person-centred care was examined by applying a validated Person Centred Nursing Framework. FINDINGS: Five main themes were identified. Participants' accounts contained descriptions of bereavement care and the presence of person-centred interventions. Contextual, professional and attitudinal factors influenced the degree to which person-centred care operated. CONCLUSION: Caring for suddenly bereaved families was important to nurses, but also a source of tension and unrest. An important consideration for person centred practice is movement away from sudden bereavement as a 'here and now' event, towards a pathway of supportive care that envisions the longer-term. Further research is required to gain a deeper understanding of person-centred care for the suddenly bereaved and the perceived effectiveness of nursing interventions. PMID- 26853503 TI - Contaminated medical lead clothes in an orthopedic specialist hospital: The potential for infection. PMID- 26853504 TI - The attitudes of healthcare professionals towards women using illicit substances in pregnancy: A cross-sectional study. AB - AIM: To assess the attitudes of healthcare professionals towards women who use substances in the maternity setting. BACKGROUND: Illicit drug use in pregnancy leads to poor maternal and neonatal outcomes. Early access to antenatal care has been shown to improve outcomes however women who use substances in pregnancy have statistically low attendance rates to appointments. Fear of stigma from healthcare professionals is a commonly stated reason for not accessing maternity health services or not disclosing substance use to care givers, however little research has been conducted which assesses stigma from a healthcare perspective. METHODS: A cross-sectional quantitative research design was implemented using a previously validated attitudinal survey tool to assess the attitudes of healthcare practitioners and final year midwifery students. Ethics approval was sought and granted by the relevant institutions. A total of 147 completed questionnaires were returned. Data was analysed using the Statistical Package for the Social Sciences and parametric testing was undertaken. RESULTS: Participants had largely positive or neutral attitudes towards women who use substances in pregnancy. Most participants agreed or strongly agreed that the care they provide to can make a real difference to outcomes. Midwifery students had significantly lower mean attitude scores, showing more positive attitudes, than any other group tested. CONCLUSION: This research provides useful insight into the attitudes of healthcare professionals. While larger scale research is needed, the positive findings of this study may work towards reducing fear of stigma as a barrier to care for women. PMID- 26853505 TI - The regulatory mechanism of ion permeation through a channelrhodopsin derived from Mesostigma viride (MvChR1). AB - The five glutamate (E) residues of transmembrane (TM)-2 of channelrhodopsin (CrChR)-2 are conserved among several members of the ChR family. A point mutation of one of them, E97, to a nonpolar alanine (E97A) reduced the photocurrent amplitude without influencing other photocurrent properties. The charge at this position is also the determinant of the Gd(3+)-dependent block of the channel. It has thus been suggested that E97 interacts with hydrated cations to facilitate their permeation and that these residues are the primary binding sites of Gd(3+). However, the counterpart of this position is alanine for MvChR1 from Mesostigma viride. Here we investigated the ion permeation and the Gd(3+)-dependent channel block of MvChR1. We found that the high-affinity binding site of Gd(3+) was absent in MvChR1, but was dependent on the negativity at this position. However, the ion permeation through the channel was markedly interfered with a negative charge at this position. Based on these findings, it is proposed that the ions can pass through the pore with minimal interaction with this position. PMID- 26853506 TI - Individual consequences of having work and family roles simultaneously in Iranian married women. AB - Because of the paucity of studies about the consequences of women's work and family responsibilities in Iran, in the present study the authors used a qualitative approach to begin to provide in-depth answers to the following question: What are the consequences of having work and family responsibilities in Iranian married women? Data were obtained from 29 participants using individual in-depth interviews conducted with 17 participants in addition to two focus groups (n = 6 per group), all conducted in the second half of 2014. All of the participants were Iranian nationals, married, and held a full-time job outside the home. Five main themes were derived from the study: "promotion of self-esteem and social status," "facing difficulties," "effort and dedication," "unfulfilled needs and non-optimal health," and "restless mind." Participants reported achieving a number of advantages for themselves and their families as a result of working outside the home; but, they also had many problems with the potential to impair various health aspects, including physical, reproductive, and mental health. Thus, it is important for Iranian health-care providers to consider the effect of the work-family interference on women. PMID- 26853507 TI - Electrochemical oxidation of the poultry manure anaerobic digested effluents for enhancing pollutants removal by Chlorella vulgaris. AB - The mechanisms and pseudo-kinetics of the electrochemical oxidation for wastewater treatment and the synergistic effect of combining algal biological treatment were investigated. NaCl, Na2SO4 and HCl were applied to compare the effect of electrolyte species on nutrients removal. NaCl was proved to be more efficient in removing ammonia ([Formula: see text]), total phosphorus (TP), total organic carbon (TOC) and inorganic carbon (IC). [Formula: see text] oxidation by using Ti/Pt-IrO2 electrodes was modelled, which indicates that the [Formula: see text] removal followed the zero-order kinetic with sufficient Cl(-) and the first order kinetic with insufficient Cl(-), respectively. The feasibility of combining electrochemical oxidation with microalgae cultivation for wastewater treatment was also determined. A 2 h electrochemical pretreatment reduced 57% [Formula: see text], 76% TP, 72% TOC and 77% IC from the digested effluent, which is applied as feedstock for algae cultivation, and resulted in increasing both the biomass production and pollutants removal efficiencies of the algal biological process. PMID- 26853508 TI - Apparent diffusion coefficient value in invasive ductal carcinoma at 3.0 Tesla: is it correlated with prognostic factors? AB - OBJECTIVE: To investigate the correlation between apparent diffusion coefficient (ADC) values and prognostic factors in patients with invasive ductal carcinoma (IDC). METHODS: 48 lesions belonging to 47 patients with histopathologically proven IDC were examined using conventional MR and diffusion-weighted imaging at a 3.0-T system. All of the patients had modified radical mastectomies or breast sparing surgery plus axillary lymph node dissection. The ADC values acquired from the ADC maps consisted of six different b-values (0, 50, 100, 500, 1000 and 1500 s mm(-2)) and were compared with the patients' ages, tumour size, histological grade of the lesions, tumour localization, lesions' distance to skin surface and nipples, the existence of axillary lymph node involvement, the number of involved axillary lymph nodes, oestrogen/progesterone receptor status, peritumoral lymphovascular invasion status and the existence of human epidermal growth factor 2 (c-erbB-2) overexpression. RESULTS: A statistically significant relationship was found regarding axillary lymph node involvement (p = 0.027), and oestrogen/progesterone receptor status (p = 0.013). No significant relationship was detected regarding other prognostic factors (p > 0.05). CONCLUSION: Among various prognostic factors, ADC values were significantly correlated with only axillary lymph node positivity and oestrogen/progesterone receptor status. ADVANCES IN KNOWLEDGE: In the present study, the relationship between ADC values of IDC lesions that are acquired at a high magnetic field (3.0 T) system by using multiple b-values and some specific prognostic factors that were not evaluated before in the medical literature was investigated. PMID- 26853509 TI - Selective magnetic resonance imaging (MRI) in invasive lobular breast cancer based on mammographic density: does it lead to an appropriate change in surgical treatment? AB - OBJECTIVE: The purpose of this study was to evaluate whether high mammographic density can be used as one of the selection criteria for MRI in invasive lobular breast cancer (ILC). METHODS: In our institute, high breast density has been used as one of the indications for performing MRI scan in patients with ILC. We divided the patients in two groups, one with MRI performed pre-operatively and other without MRI. We compared their surgical procedures and analyzed whether surgical plan was altered after MRI. In case of alteration of plan, we analyzed whether the change was adequate by comparing post-operative histological findings. RESULTS: Between 2011 and 2015, there were a total of 1601 breast cancers with 97 lobular cancers, out of which 36 had pre-operative MRI and 61 had no MRI scan. 12 (33.3%) had mastectomy following MRI, out of which 9 (25%) had change in surgical plan from conservation to mastectomy following MRI. There were no unnecessary mastectomies in the MRI group. However, utilization of MRI in this cohort of patients did not reduce reoperation rate (19.3%). Lobular carcinoma in situ (LCIS) was identified in 60% of reoperations on post-surgical histology. Patients in the "No MRI" group had higher mastectomy rate 26 (42.6%), which was again appropriate. CONCLUSION: High mammographic density is a useful risk stratification criterion for selective MRI in ILC within a multidisciplinary team meeting setting. Provided additional lesions identified on MRI are confirmed with biopsy, pre-operative MRI does not cause unnecessary mastectomies. Used in this selective manner, reoperation rates were not eliminated, albeit reduced when compared to literature. ADVANCES IN KNOWLEDGE: High mammographic breast density can be used as one of the selection criteria for pre-operative MRI in ILC without an increase in inappropriate mastectomies with potential time and cost savings. In this cohort, re-excisions were not reduced markedly with pre-operative MRI. PMID- 26853510 TI - Dose reduction in 64-row whole-body CT in multiple trauma: an optimized CT protocol with iterative image reconstruction on a gemstone-based scintillator. AB - OBJECTIVE: Evaluation of potential dose savings by implementing adaptive statistical iterative reconstruction (ASiR) on a gemstone-based scintillator in a clinical 64-row whole-body CT (WBCT) protocol after multiple trauma. METHODS: Dose reports of 152 WBCT scans were analysed for two 64-row multidetector CT scanners (Scanners A and B); the main scanning parameters were kept constant. ASiR and a gemstone-based scintillator were used in Scanner B, and the noise index was adjusted (head: 5.2 vs 6.0; thorax/abdomen: 29.0 vs 46.0). The scan length, CT dose index (CTDI) and dose-length product (DLP) were analysed. The estimated mean effective dose was calculated using normalized conversion factors. Student's t-test was used for statistics. RESULTS: Both the mean CTDI (mGy) (Scanner A: 53.8 +/- 2.0, 10.3 +/- 2.5, 14.4 +/- 3.7; Scanner B: 48.7 +/- 2.2, 7.1 +/- 2.3, 9.1 +/- 3.6; p < 0.001, respectively) and the mean DLP (mGy cm) (Scanner A: 1318.9 +/- 167.8, 509.3 +/- 134.7, 848.8 +/- 254.0; Scanner B: 1190.6 +/- 172.6, 354.6 +/- 128.3, 561.0 +/- 246.7; p < 0.001, respectively) for the head, thorax and abdomen were significantly reduced with Scanner B. There was no relevant difference in scan length. The total mean effective dose (mSv) was significantly decreased with Scanner B (24.4 +/- 6.0, 17.2 +/- 5.8; p < 0.001). CONCLUSION: The implementation of ASiR and a gemstone-based scintillator allows for significant dose savings in a clinical WBCT protocol. ADVANCES IN KNOWLEDGE: Recent technical developments can significantly reduce radiation dose of WBCT in multiple trauma. Dose reductions of 10-34% can be achieved. PMID- 26853511 TI - Dissipative particle dynamics simulation study of poly(2-oxazoline)-based multicompartment micelle nanoreactor. AB - We investigate multicompartment micelles consisting of poly(2-oxazoline)-based triblock copolymers for nanoreactor applications, using the DPD simulation method to characterize the internal structure of the micelles and the distribution of reactant. The DPD simulation parameters are determined from the Flory-Huggins interaction parameter (chiFH). From the snapshots of the micellar structures and radial distribution function of polymer blocks, it is clearly presented that the micelle is multicompartmental. In addition, by implementing the DPD simulations in the presence of reactants, it is found that Reac-C4 and Reac-OPh are associate well with the hydrophilic shell of the micelle, whereas the other two reactants, Reac-Ph and Reac-Cl, are not incorporated into the micelle. From our DPD simulations, we confirm that the miscibility (solubility) of reactant with the micelle has a strong correlation with the rate of hydrolysis kinetic resolution. Utilizing accurate methods evaluating accurate chiFH parameters for molecular interactions in micelle system, this DPD simulation can have a great potential to predict the structures of micelles consisting of designed multiblock copolymers for useful reactions. PMID- 26853512 TI - Room-Temperature Quantum Coherence and Rabi Oscillations in Vanadyl Phthalocyanine: Toward Multifunctional Molecular Spin Qubits. AB - Here we report the investigation of the magnetic relaxation and the quantum coherence of vanadyl phthalocyanine, VOPc, a multifunctional and easy-processable potential molecular spin qubit. VOPc in its pure form (1) and its crystalline dispersions in the isostructural diamagnetic host TiOPc in different stoichiometric ratios, namely VOPc:TiOPc 1:10 (2) and 1:1000 (3), were investigated via a multitechnique approach based on the combination of alternate current (AC) susceptometry, continuous wave, and pulsed electron paramagnetic resonance (EPR) spectroscopy. AC susceptibility measurements revealed a linear increase of the relaxation rate with temperature up to 20 K, as expected for a direct mechanism, but tau remains slow over a very wide range of applied static field values (up to ~5 T). Pulsed EPR spectroscopy experiments on 3 revealed quantum coherence up to room temperature with T(m) ~1 MUs at 300 K, representing the highest value obtained to date for molecular electronic spin qubits. Rabi oscillations are observed in this nuclear spin-active environment ((1)H and (14)N nuclei) at room temperature also for 2, indicating an outstanding robustness of the quantum coherence in this molecular semiconductor exploitable in spintronic devices. PMID- 26853513 TI - Harnessing the bone-seeking ability of Ca(II)-like metal ions in the treatment of metastatic cancer and resorption disorders. AB - Metal ions are naturally retained by skeletal tissues in living systems because of their high affinity for the hydroxyapatite-like mineral matrix that makes up cortical bone. This is particularly true for metal ions that bear a close resemblance to calcium(ii) (such as the lanthanides or alkaline earth metals), and in a few key cases this targeting ability has been exploited in order to develop medicinal agents that are intended to treat bones which have become diseased. In this review, we focus on two areas where this has been particularly effective: first is in the diagnosis and therapy of metastatic bone cancer, in which radioactive metal ions including (99m)Tc, (153)Sm, and (223)Ra are used to image, alleviate, and ablate harmful cancerous legions with good specificity versus healthy tissues; second is the use of trivalent lanthanides to treat osteoporosis, an emerging concept which has gathered significance over the last 15 years, and is now entering preclinical trials with carefully designed systems. PMID- 26853514 TI - Gram-scale production of plasmid pUDK-HGF with current good manufacturing practices for gene therapy of critical limb ischemia. AB - The demand of a plasmid encoding human hepatocyte growth factor gene (pUDK-HGF) in large quantities at high purity and concentration has increased for gene therapy of critical limb ischemia (CLI) in clinical trials. In this article, we produced pUDK-HGF in compliance with current good manufacturing practices at gram scale. The process included a 50-L batch fermentation, continuous alkaline lysis, and integrated three-step chromatography on Sepharose 6 Fast Flow, PlasmidSelect Xtra, and Source 15Q. The production process has been scaled up to yield 4.24 +/- 0.41 g of pharmaceutical pUDK-HGF from 1.0 kg bacterial cell paste and the overall yield reached range from 58.37 to 66.70%. The final pUDK-HGF product exhibited high purity with supercoiled percentage of > 95.8% and undetectable residual RNA, contaminated protein, and bacterial endotoxin. The phase I clinical study indicates that intramuscular injection of pUDK-HGF is safe, well tolerated, and may provide symptomatic relief to CLI patients. These results show that our manufacturing process of pUDK-HGF is efficient in producing pharmaceutical-grade plasmid DNA and is safe for clinical applications. PMID- 26853515 TI - Management of granulomatous cerebral aspergillosis in immunocompetent adult patients: a review. AB - Cerebral aspergillosis, is an infrequent, opportunistic infection of the central nervous system that accounts for 5-10% of all intracranial fungal pathology. It is uncommon in immunocompetent patients and has a significant disease burden, with high morbidity and mortality, even with appropriate treatment. Basic principles of abscess management should be employed, including aspiration and targeted anti-fungal therapy for 12-18 months. However, reported outcomes with a purely minimally invasive approach are poor and there should be a low threshold for surgical excision, especially in resource poor settings and in patients with deteriorating neurology harbouring sizeable masses. Evidence favouring gross total excision over subtotal resection is lacking, however. It is notable that these recommendations are largely based on retrospective case series and isolated case reports. There is a need therefore for international collaboration to evaluate management strategies for immunocompetent patients with cerebral aspergillosis. PMID- 26853516 TI - A comparative study of photoinduced deformation in azobenzene containing polymer films. AB - In this paper two groups supporting different views on the mechanism of light induced polymer deformation argue about the respective underlying theoretical conceptions, in order to bring this interesting debate to the attention of the scientific community. The group of Prof. Nicolae Hurduc supports the model claiming that the cyclic isomerization of azobenzenes may cause an athermal transition of the glassy azobenzene containing polymer into a fluid state, the so called photo-fluidization concept. This concept is quite convenient for an intuitive understanding of the deformation process as an anisotropic flow of the polymer material. The group of Prof. Svetlana Santer supports the re orientational model where the mass-transport of the polymer material accomplished during polymer deformation is stated to be generated by the light-induced re orientation of the azobenzene side chains and as a consequence of the polymer backbone that in turn results in local mechanical stress, which is enough to irreversibly deform an azobenzene containing material even in the glassy state. For the debate we chose three polymers differing in the glass transition temperature, 32 degrees C, 87 degrees C and 95 degrees C, representing extreme cases of flexible and rigid materials. Polymer film deformation occurring during irradiation with different interference patterns is recorded using a homemade set up combining an optical part for the generation of interference patterns and an atomic force microscope for acquiring the kinetics of film deformation. We also demonstrated the unique behaviour of azobenzene containing polymeric films to switch the topography in situ and reversibly by changing the irradiation conditions. We discuss the results of reversible deformation of three polymers induced by irradiation with intensity (IIP) and polarization (PIP) interference patterns, and the light of homogeneous intensity in terms of two approaches: the re-orientational and the photo-fluidization concepts. Both agree in that the formation of opto-mechanically induced stresses is a necessary prerequisite for the process of deformation. Using this argument, the deformation process can be characterized either as a flow or mass transport. PMID- 26853517 TI - Visual and efficient immunosensor technique for advancing biomedical applications of quantum dots on Salmonella detection and isolation. AB - It is a great challenge in nanotechnology for fluorescent nanobioprobes to be applied to visually detect and directly isolate pathogens in situ. A novel and visual immunosensor technique for efficient detection and isolation of Salmonella was established here by applying fluorescent nanobioprobes on a specially designed cellulose-based swab (a solid-phase enrichment system). The selective and chromogenic medium used on this swab can achieve the ultrasensitive amplification of target bacteria and form chromogenic colonies in situ based on a simple biochemical reaction. More importantly, because this swab can serve as an attachment site for the targeted pathogens to immobilize and immunologically capture nanobioprobes, our mAb-conjugated QD bioprobes were successfully applied on the solid-phase enrichment system to capture the fluorescence of targeted colonies under a designed excitation light instrument based on blue light emitting diodes combined with stereomicroscopy or laser scanning confocal microscopy. Compared with the traditional methods using 4-7 days to isolate Salmonella from the bacterial mixture, this method took only 2 days to do this, and the process of initial screening and preliminary diagnosis can be completed in only one and a half days. Furthermore, the limit of detection can reach as low as 10(1) cells per mL Salmonella on the background of 10(5) cells per mL non Salmonella (Escherichia coli, Proteus mirabilis or Citrobacter freundii, respectively) in experimental samples, and even in human anal ones. The visual and efficient immunosensor technique may be proved to be a favorable alternative for screening and isolating Salmonella in a large number of samples related to public health surveillance. PMID- 26853518 TI - Systemic effects of surgical intervention on disease activity, daily function, and medication in patients with rheumatoid arthritis. AB - OBJECTIVES: Although tight control of rheumatoid arthritis (RA) has been achieved through the development of effective medication, surgical intervention is still required for a certain subpopulation of patients. To examine the systemic effects of orthopaedic surgery, we evaluated improvements in disease activity, daily function, and medication after surgery. METHOD: A prospective cohort study was conducted in 196 cases of elective orthopaedic surgery in 150 patients with RA from January 2011 to March 2014 in our institution. The 28-joint count Disease Activity Score based on erythrocyte sedimentation rate (DAS28-ESR) and modified Health Assessment Questionnaire (mHAQ) scores just before surgery and at 6 and 12 months after surgery were examined prospectively. Concomitant medications were also investigated. RESULTS: Significant improvement was seen in the DAS28-ESR and mHAQ scores for replacement surgery in both the upper and lower extremities, and for arthroplasty/arthrodesis in the upper extremities at the 12-month follow-up. Partial mHAQ scores for the lower extremities were significantly reduced in lower replacement surgery, and partial mHAQ scores for the upper extremities were significantly reduced in upper arthroplasty/arthrodesis surgery. Although the use of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) did not decrease after surgery, the dose of prednisolone (PSL) decreased significantly at 12 months after surgery, especially in the well-controlled group and in surgical procedures in the lower extremities. CONCLUSIONS: Elective orthopaedic surgery improves both systemic disease activity and general functional impairment. Orthopaedic surgery is effective in reducing the amount of medication required postoperatively. PMID- 26853519 TI - Factors associated with participation frequency and satisfaction among people applying for a housing adaptation grant. AB - BACKGROUND: People applying for a housing adaptation (HA) grant are at great risk of participation restrictions due to declining capacity and environmental barriers. AIM: To investigate the association of person-, environment-, and activity-related factors with participation frequency and satisfaction among people applying for a housing adaptation grant. MATERIAL AND METHODS: Baseline cross-sectional data were collected during home visits (n = 128). The association between person-, environment-, and activity-related factors and participation frequency and satisfaction was analysed using logistic regressions. RESULTS: The main result is that frequency of participation outside the home is strongly associated with dependence in activities of daily living (ADL) and cognitive impairments, while satisfaction with participation outside the home is strongly associated with self-reported health. Moreover, aspects of usability in the home were associated with frequency of participation outside the home and satisfaction with participation in the home and outside the home alone. CONCLUSION: Dependence in ADL, cognitive impairments, self-rated health, and aspects of usability are important factors contributing to participation frequency and satisfaction among people applying for a housing adaptation grant, particularly outside the home. SIGNIFICANCE: Our findings indicate that more attention should be directed towards activity-related factors to facilitate participation among HA applicants, inside and outside the home. PMID- 26853520 TI - Movements and habitat preferences of pests help to improve population control: the case of common brushtail possums in a New Zealand dryland ecosystem. AB - BACKGROUND: Introduced brushtail possums are controlled in New Zealand to mitigate their spread of bovine tuberculosis in livestock. Given the low rainfall and extreme variation in seasonal temperatures in dryland areas of the South Island, the habitats of possums in these areas differ in many respects from those in the rest of New Zealand. We investigated the movements and habitat preferences of possums at two dryland sites to identify where they aggregate following population control by using GPS collars and cards chewed by possums. At one site, possum numbers were reduced from high levels by 65%, and at the other site, possums had already been reduced to low levels for some time beforehand but were further reduced to maintain them at low levels. This resulted in different possum densities. RESULTS: Possum home ranges were about 3 times smaller at the higher density site, but average ranges expanded by 27% following initial control. Home ranges were already large at the lower-density site but did not expand further after maintenance control. No preference for habitat types was apparent at the higher-density site, but at the lower-density site possums selected rock and shrubby habitats and avoided open grassy areas. CONCLUSIONS: Home range sizes and habitat preferences were density dependent: the lower the density, the larger was the home range; and habitat preferences were highly variable between individuals, but less so for possums at low density. Preference for shrubs and rocks is likely to benefit population control if population control devices are focused on these habitat types. (c) 2016 Society of Chemical Industry. PMID- 26853521 TI - Long-chain unsaturated fatty acids reduce the transcriptional activity of the rat follicle-stimulating hormone beta-subunit gene. AB - Here, we assessed the effects of long-chain fatty acids (LCFAs) and the LCFA receptor agonist GW9508 on the transcription of the gonadotropin subunit genes Cga, Lhb and Fshb because LCFA receptor GPR120 was observed in mouse gonadotropes in our recent study. A transcription assay using LbetaT2 cells demonstrated that LCFAs, oleic acid, alpha-linolenic acid, docosahexaenoic acid and palmitate, repressed the expression of Cga, Lhb, and Fshb at concentrations between 50 and 100 uM. On the other hand, treatment with 10 uM unsaturated LCFAs, oleic acid, alpha-linolenic acid and docosahexaenoic acid, repressed only Fshb expression, while the same dose of a saturated LCFA, palmitate, had no effect on the expression of gonadotropin subunit genes. Furthermore, GW9508 did not affect promoter activity. Next, we examined deletion mutants of the upstream region of Fshb and found that the upstream regulatory region (-2824 to -2343 bp) of Fshb was responsible for the notable repression by 10 uM unsaturated LCFAs. Our results suggest that the upstream region of Fshb is susceptible to unsaturated LCFAs. In addition, unsaturated LCFAs play a role in repressing Fshb expression through the distal -2824 to -2343 bp region, which might be independent of the LCFA receptor GPR120 pathway. PMID- 26853523 TI - Spatiotemporal choreography of chromosome and megaplasmids in the Sinorhizobium meliloti cell cycle. AB - A considerable share of bacterial species maintains multipartite genomes. Precise coordination of genome replication and segregation with cell growth and division is vital for proliferation of these bacteria. The alpha-proteobacterium Sinorhizobium meliloti possesses a tripartite genome composed of one chromosome and the megaplasmids pSymA and pSymB. Here, we investigated the spatiotemporal pattern of segregation of these S. meliloti replicons at single cell level. Duplication of chromosomal and megaplasmid origins of replication occurred spatially and temporally separated, and only once per cell cycle. Tracking of FROS (fluorescent repressor operator system)-labelled origins revealed a strict temporal order of segregation events commencing with the chromosome followed by pSymA and then by pSymB. The repA2B2C2 region derived from pSymA was sufficient to confer the spatiotemporal behaviour of this megaplasmid to a small plasmid. Altering activity of the ubiquitous prokaryotic replication initiator DnaA, either positively or negatively, resulted in an increase in replication initiation events or G1 arrest of the chromosome only. This suggests that interference with DnaA activity does not affect replication initiation control of the megaplasmids. PMID- 26853524 TI - Systematic review and meta-analysis of acupuncture to reduce cancer-related pain. AB - We conducted a systematic review and meta-analysis to evaluate the effects of acupuncture on malignancy-related, chemotherapy (CT)- or radiation therapy (RT) induced, surgery-induced, and hormone therapy (HT)-induced pain. Randomised controlled trials (RCTs) examining the effects of acupuncture on cancer-related pain were reached from the EMBASE, PubMed, PsycINFO, Cochrane Central Register of Controlled Trials, CINAHL, Airiti library, Taiwan Electrical Periodical Service, Wanfang Data (a Chinese database) and China Knowledge Resource Integrated Database from inception through June 2014. Heterogeneity, moderator analysis, publication bias and risk of bias associated with the included studies were examined. A total of 29 RCTs yielding 36 effect sizes were included. The overall effect of acupuncture on cancer-related pain was -0.45 [95% confidence interval (CI) = -0.63 to -0.26]. The subanalysis indicated that acupuncture relieved malignancy-related and surgery-induced pain [effect size (g) = -0.71, and -0.40; 95% CI = -0.94 to -0.48, and -0.69 to -0.10] but not CT- or RT-induced and HT induced pain (g = -0.05, and -0.64, 95% CI = -0.33 to 0.24, and -1.55 to 0.27). Acupuncture is effective in relieving cancer-related pain, particularly malignancy-related and surgery-induced pain. Our findings suggest that acupuncture can be adopted as part of a multimodal approach for reducing cancer related pain. PMID- 26853525 TI - Association between parity and fistula location in women with obstetric fistula: a multivariate regression analysis. AB - OBJECTIVE: To compare primiparous and multiparous women who develop obstetric fistula (OF) and to assess predictors of fistula location. DESIGN: Cross sectional study. SETTING: Fistula Care Centre at Bwaila Hospital, Lilongwe, Malawi. POPULATION: Women with OF who presented between September 2011 and July 2014 with a complete obstetric history were eligible for the study. METHODS: Women with OF were surveyed for their obstetric history. Women were classified as multiparous if prior vaginal or caesarean delivery was reported. The location of the fistula was determined at operation: OF involving the urethra, bladder neck, and midvagina were classified as low; OF involving the vaginal apex, cervix, uterus, and ureters were classified as high. MAIN OUTCOME MEASURES: Demographic information was compared between primiparous and multiparous women using chi squared and Mann-Whitney U-tests. Multivariate logistic regression models were implemented to assess the relationship between variables of interest and fistula location. RESULTS: During the study period, 533 women presented for repair, of which 452 (84.8%) were included in the analysis. The majority (56.6%) were multiparous when the fistula formed. Multiparous women were more likely to have laboured <1 day (62.4 versus 44.5%, P < 0.001), delivered a live-born infant (26.8 versus 17.9%, P = 0.026), and have a high fistula location (37.5 versus 11.2%, P < 0.001). Multiparity [adjusted odds ratio (aOR) = 4.55, 95% confidence interval (CI) 2.27-9.12)] and history of caesarean delivery (aOR = 4.11, 95% CI 2.45-6.89) were associated with development of a high fistula. CONCLUSIONS: Multiparity was common in our cohort, and these women were more likely to have a high fistula. Additional research is needed to understand the aetiology of high fistula including potential iatrogenic causes. TWEETABLE ABSTRACT: Multiparity and caesarean delivery were associated with a high tract fistula in our Malawian cohort. PMID- 26853522 TI - MicroRNA expression and its association with DNA repair in preimplantation embryos. AB - Active DNA repair pathways are crucial for preserving genomic integrity and are likely among the complex mechanisms involved in the normal development of preimplantation embryos. MicroRNAs (miRNA), short non-coding RNAs, are key regulators of gene expression through the post-transcriptional and post translational modification of mRNA. The association of miRNA expression with infertility or polycystic ovarian syndrome has been widely investigated; however, there are limited data regarding the importance of miRNA regulation in DNA repair during preimplantation embryo development. In this article, we review normal miRNA biogenesis and consequences of aberrant miRNA expression in the regulation of DNA repair in gametes and preimplantation embryos. PMID- 26853526 TI - Adverse family experiences during childhood and adolescent obesity. AB - OBJECTIVE: To evaluate the association between adverse family experiences (AFEs) during childhood and adolescent obesity and to determine populations at highest risk for AFEs. METHODS: A cross-sectional analysis was performed of the 2011-2012 National Survey of Children's Health, including children aged 10-17 years. Weighted estimates of 31,258,575 children were based on interviews with 42,239 caregivers. Caregiver reports of nine psychosocial risk factors measured AFEs during childhood. Adolescent overweight and obesity were derived by caregiver reported child height and weight. RESULTS: Nearly one-third (30.5%) of children had experienced >=2 AFEs, with geographic variation by state. The prevalence of obesity among children experiencing >=2 AFEs was 20.4%, when compared with 12.5% among children with 0 AFEs. Adjusted survey regression models were controlled for child, parent, household, and neighborhood characteristics. Children with >=2 AFEs in childhood were more likely to have obesity (AOR = 1.8; 95% CI = 1.47 2.17; P < 0.001) than those with no AFEs, with Non-Hispanic, White children most affected. CONCLUSIONS: Adolescents in this national sample who were exposed to greater numbers of AFEs in childhood also had higher rates of overweight and obesity. Geographic variation and differential associations based on race/ethnicity identified children at greatest risk. PMID- 26853527 TI - The Small GTP-Binding Protein Rhes Influences Nigrostriatal-Dependent Motor Behavior During Aging. AB - BACKGROUND: Here we aimed to evaluate: (1) Rhes mRNA expression in mouse midbrain, (2) the effect of Rhes deletion on the number of dopamine neurons, (3) nigrostriatal-sensitive behavior during aging in knockout mice. METHODS: Radioactive in situ hybridization was assessed in adult mice. The beam-walking test was executed in 3-, 6- and 12-month-old mice. Immunohistochemistry of midbrain tyrosine hydroxylase (TH)-positive neurons was performed in 6- and 12 month-old mice. RESULTS: Rhes mRNA is expressed in TH-positive neurons of SNpc and the ventral tegmental area. Moreover, lack of Rhes leads to roughly a 20% loss of nigral TH-positive neurons in both 6- and 12-month-old mutants, when compared with their age-matched controls. Finally, lack of Rhes triggers subtle alterations in motor performance and coordination during aging. CONCLUSIONS: Our findings indicate a fine-tuning role of Rhes in regulating the number of TH positive neurons of the substantia nigra and nigrostriatal-sensitive motor behavior during aging. PMID- 26853528 TI - Chaperone complex BAG2-HSC70 regulates localization of Caenorhabditis elegans leucine-rich repeat kinase LRK-1 to the Golgi. AB - Mutations in LRRK2 are linked to autosomal dominant forms of Parkinson's disease. We identified two human proteins that bind to LRRK2: BAG2 and HSC70, which are known to form a chaperone complex. We characterized the role of their Caenorhabditis elegans homologues, UNC-23 and HSP-1, in the regulation of LRK-1, the sole homologue of human LRRK2. In C. elegans, LRK-1 determines the polarized sorting of synaptic vesicle (SV) proteins to the axons by excluding SV proteins from the dendrite-specific transport machinery in the Golgi. In unc-23 mutants, SV proteins are localized to both presynaptic and dendritic endings in neurons, a phenotype also observed in lrk-1 deletion mutants. Furthermore, we isolated mutations in the hsp-1 gene that can suppress the unc-23, but not the lrk-1 defect. We show that UNC-23 determines LRK-1 localization to the Golgi apparatus in cooperation with HSP-1. These results describe a chaperone-dependent mechanism through which LRK-1 localization is regulated. PMID- 26853529 TI - Variant haploinsufficiency and phenotypic non-penetrance in PRPF31-associated retinitis pigmentosa. AB - Retinitis pigmentosa (RP) is a genetically heterogenous group of inherited disorders, characterized by death of the retinal photoreceptor cells, leading to progressive visual impairment. One form of RP is caused by mutations in the ubiquitously expressed splicing factor, PRPF31, this form being known as RP11. An intriguing feature of RP11 is the presence of non-penetrance, which has been observed in the majority of PRPF31 mutation-carrying families. In contrast to variable expressivity, which is highly pervasive, true non-penetrance is a very rare phenomenon in Mendelian disorders. In this article, the molecular mechanisms underlying phenotypic non-penetrance in RP11 are explored. It is an elegant example of how our understanding of monogenic disorders has evolved from studying only the disease gene, to considering a mutation on the genetic background of the individual - the logical evolution in this genomic era. PMID- 26853530 TI - The mechanisms whereby the green alga Chlorella ohadii, isolated from desert soil crust, exhibits unparalleled photodamage resistance. AB - Excess illumination damages the photosynthetic apparatus with severe implications with regard to plant productivity. Unlike model organisms, the growth of Chlorella ohadii, isolated from desert soil crust, remains unchanged and photosynthetic O2 evolution increases, even when exposed to irradiation twice that of maximal sunlight. Spectroscopic, biochemical and molecular approaches were applied to uncover the mechanisms involved. D1 protein in photosystem II (PSII) is barely degraded, even when exposed to antibiotics that prevent its replenishment. Measurements of various PSII parameters indicate that this complex functions differently from that in model organisms and suggest that C. ohadii activates a nonradiative electron recombination route which minimizes singlet oxygen formation and the resulting photoinhibition. The light-harvesting antenna is very small and carotene composition is hardly affected by excess illumination. Instead of succumbing to photodamage, C. ohadii activates additional means to dissipate excess light energy. It undergoes major structural, compositional and physiological changes, leading to a large rise in photosynthetic rate, lipids and carbohydrate content and inorganic carbon cycling. The ability of C. ohadii to avoid photodamage relies on a modified function of PSII and the dissipation of excess reductants downstream of the photosynthetic reaction centers. The biotechnological potential as a gene source for crop plant improvement is self evident. PMID- 26853531 TI - Position-effect variegation revisited: HUSHing up heterochromatin in human cells. AB - Much of what we understand about heterochromatin formation in mammals has been extrapolated from forward genetic screens for modifiers of position-effect variegation (PEV) in the fruit fly Drosophila melanogaster. The recent identification of the HUSH (Human Silencing Hub) complex suggests that more recent evolutionary developments contribute to the mechanisms underlying PEV in human cells. Although HUSH-mediated repression also involves heterochromatin spreading through the reading and writing of the repressive H3K9me3 histone modification, clear orthologues of HUSH subunits are not found in Drosophila but are conserved in vertebrates. Here we compare the insights into the mechanisms of PEV derived from genetic screens in the fly, the mouse and in human cells, review what is currently known about the HUSH complex and discuss the implications of HUSH-mediated silencing for viral latency. Future studies will provide mechanistic insight into HUSH complex function and reveal the relationship between HUSH and other epigenetic silencing complexes. PMID- 26853532 TI - How to convey a diagnosis of skin cancer: patient preferences. PMID- 26853533 TI - Heat shock proteins in hepatocellular carcinoma: Molecular mechanism and therapeutic potential. AB - Heat shock proteins (HSPs) are highly conserved proteins, which are expressed at low levels under normal conditions, but significantly induced in response to cellular stresses. As molecular chaperones, HSPs play crucial roles in protein homeostasis, apoptosis, invasion and cellular signaling transduction. The induction of HSPs is an important part of heat shock response, which could help cancer cells to adapt to stress conditions. Because of the constant stress condition in tumor microenvironment, HSPs overexpression is widely reported in many human cancers. In light of the significance of HSPs for cancer cells to survive and obtain invasive phenotype under stress condition, HSPs are often associated with poor prognosis and treatment resistance in many types of human cancers. It has been described that upregulation of HSPs may serve as diagnostic and prognostic markers in hepatocellular carcinoma (HCC). Targeting HSPs with specific inhibitor alone or in combination with chemotherapy regimens holds promise for the improvement of outcomes for HCC patients. In this review, we summarize the expression profiles, functions and molecular mechanisms of HSPs (HSP27, HSP70 and HSP90) as well as a HSP-like protein (clusterin) in HCC. In addition, we address progression and challenges in targeting these HSPs as novel therapeutic strategies in HCC. PMID- 26853534 TI - Retraction. PMID- 26853535 TI - Erratum. PMID- 26853536 TI - Chip-Scale Fabrication of High-Q All-Glass Toroidal Microresonators for Single Particle Label-Free Imaging. AB - Whispering-gallery-mode microresonators enable materials for single-molecule label-free detection and imaging because of their high sensitivity to their micro environment. However, fabrication and materials challenges prevent scalability and limit functionality. All-glass on-chip microresonators significantly reduce these difficulties. Construction of all-glass toroidal microresonators with high quality factor and low mode volume is reported and these are used as platforms for label-free single-particle imaging. PMID- 26853537 TI - On the Role of Viscosity in the Eyring Equation. AB - Transition-state theory allows for the characterization of kinetic processes in terms of enthalpy and entropy of activation by using the Eyring equation. However, for reactions in solution, it fails to take the change of viscosity of solvents with temperature into account. A second-generation unidirectional rotary molecular motor was used as a probe to study the effects of temperature-dependent viscosity changes upon unimolecular thermal isomerization processes. By combining the free-volume model with transition-state theory, a modified version of the Eyring equation was derived, in which the rate is expressed in terms of both temperature and viscosity. PMID- 26853538 TI - Associations Between Recent Heavy Drinking and Dorsal Anterior Cingulate N Acetylaspartate and Glutamate Concentrations in Non-Treatment-Seeking Individuals with Alcohol Dependence. AB - BACKGROUND: Proton magnetic resonance spectroscopy ((1) H-MRS) studies have consistently found abnormal brain concentrations of N-acetylaspartate (NAA) and glutamate in individuals with alcohol use disorders (AUD) relative to light drinkers. However, most such studies have focused on individuals in treatment for severe alcohol dependence (AD), and few studies have investigated associations between neurochemical concentrations and recent alcohol consumption. This study focused on associations between recent drinking and prefrontal neurometabolite concentrations in nonsevere, non-treatment-seeking individuals with AUD. METHODS: Nineteen treatment-naive alcohol-dependent individuals aged 21 to 40 completed a (1) H-MRS scan. Single-voxel (1) H-MRS spectra were acquired in dorsal anterior cingulate cortex (dACC) using a 2-dimensional J-resolved point resolved spectroscopy sequence. Associations between recent heavy drinking, assessed using the Timeline FollowBack, and dACC metabolite concentrations were estimated via regression controlling for within-voxel tissue composition. RESULTS: Participants provided a negative breathalyzer reading and reported between 1 and 5 days (M = 2.45, SD = 1.23) since their last drink. Number of heavy drinking days in the 14 days preceding the scan (M = 4.84, SD = 3.32) was significantly inversely associated with both glutamate/water (beta = -0.63, t(17) = -3.37, p = 0.004) and NAA/water concentrations (beta = -0.59, t(17) = -2.98, p = 0.008). CONCLUSIONS: This study extends the literature by demonstrating inverse associations between recent heavy drinking and dACC glutamate and NAA concentrations in a sample of nonsevere, non-treatment-seeking individuals with AD. These findings may support the hypothesis that amount of recent alcohol consumption may account for differences in neuronal metabolism, even in nonsevere, non-treatment-seeking alcoholics. PMID- 26853539 TI - Development of oligonucleotide microarrays for simultaneous multi-species identification of Phellinus tree-pathogenic fungi. AB - Polyporoid Phellinus fungi are ubiquitously present in the environment and play an important role in shaping forest ecology. Several species of Phellinus are notorious pathogens that can affect a broad variety of tree species in forest, plantation, orchard and urban habitats; however, current detection methods are overly complex and lack the sensitivity required to identify these pathogens at the species level in a timely fashion for effective infestation control. Here, we describe eight oligonucleotide microarray platforms for the simultaneous and specific detection of 17 important Phellinus species, using probes generated from the internal transcribed spacer regions unique to each species. The sensitivity, robustness and efficiency of this Phellinus microarray system was subsequently confirmed against template DNA from two key Phellinus species, as well as field samples collected from tree roots, trunks and surrounding soil. This system can provide early, specific and convenient detection of Phellinus species for forestry, arboriculture and quarantine inspection, and could potentially help to mitigate the environmental and economic impact of Phellinus-related diseases. PMID- 26853540 TI - Virulence of representative Japanese Francisella tularensis and immunologic consequences of infection in mice. AB - Francisella tularensis, which causes tularemia, is widely distributed in the Northern hemisphere. F. tularensis strains isolated in Japan are genetically unique from non-Japanese strains; however, their phenotypic properties have not been well studied. Thus, mice were infected with representative Japanese strains of F. tularensis and their virulence and mouse immune responses to them assessed. Of four representative Japanese strains, the Ebina, Jap and Tsuchiya strains were susceptible to H2 O2 and did not grow well intracellularly. Only Yama strain grew intracellularly and was lethal to mice. Infection with Yama strain resulted in drastic increases in IFN-gamma, CD4 and CD8 double-positive T cells and Th1 cells (CD3, CD4 and Tim3-positive cells), and a decrease in the ratio of CD8-positive CD4-negative T cells in mice. C57BL/6J mice that survived infection produced IgM antibodies to LPS and IgG2c antibodies to 43, 19 and 17 kDa proteinase K sensitive components. These data are valuable for understanding the phenotypic properties of F. tularensis in Japan. PMID- 26853541 TI - Papain immobilized polyurethane as an ureteral stent material. AB - Long term use of polyurethane-based ureteral stent is hampered by the development of infection due to the formation of bacterial biofilm and salt deposition. Here papain, is covalently immobilized to polyurethane using glutarldehyde and is investigated as a possible anti-infective ureteral stent material. Fourier transform infrared spectrum confirmed its immobilization. Immobilized enzyme retained 85% of the activity of the free enzyme and about 12% loss of enzyme was observed from the polymer surface in one month. The modified polyurethane showed 8 log reduction in Staphylococcus aureus and 7 log reduction in Escherichia coli live colonies and 3-4 times decrease in the protein and carbohydrate in the biofilms than bare polymer. The amount of calcium and magnesium salts deposited on the polymer surface reduced by 40% after enzyme immobilization. 80% of L6 myoblast cells were viable on this material which indicated that it was noncytotoxic. A linear regression equation with hydrophilicity of the polymer surface and the cell surface hydrophobicity as the two independent variables was able to predict the number of live cells attached on the modified PU. This study indicated the possibility of using such an approach to overcome the problems of ureteral stent associated biofilm and salt encrustation. PMID- 26853544 TI - Accelerating Medicines Partnership: Alzheimer's Disease (AMP-AD) Knowledge Portal Aids Alzheimer's Drug Discovery through Open Data Sharing. PMID- 26853543 TI - Public health risks and benefits associated with breast milk and infant formula consumption. AB - The safety and quality of infant milk, whether it is breast milk (BM) or infant formula (IF), are a major concern for parents and public health authorities. BM is recommended as the gold standard at WHO level. However, nowadays IF appears as an essential alternative in Western countries, challenging producers to optimize nutritional quality and safety of IF. The aim of the present article is to give an overview on the assessment and comparison of risks and benefits associated with BM and IF consumption. To date, this intensively debated subject has been mainly investigated. It has been shown that both diets could be sources of beneficial health effects in terms of nutrition and also risks in terms of chemical safety. Moreover, microbiologists have demonstrated that IF consumption can cause illness due to product contamination or inappropriate milk preparation. The article concludes on the bottlenecks and gaps that should be investigated to further progress the quantification of the impact of early diet on infant health. Performing a multi-disciplinary risk-benefit assessment with DALY as endpoint might be a future option to help prioritize management options. PMID- 26853542 TI - Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver. AB - Keratins, formerly known as cytokeratins, are the major epithelial-specific subgroup of intermediate filament proteins. Adult hepatocytes express keratin polypeptides 8 and 18 (K8/K18), whereas cholangiocytes express K8/K18 and keratins 7 and 19 (K7/K19). Keratins function primarily to protect hepatocytes from apoptosis and necrosis, which was revealed using several genetic mouse models. This cytoprotective function was further clarified by the identification of natural human keratin variants that are normally silent, but become pathogenic by predisposing their carriers to apoptosis during acute or chronic liver injury mediated by toxins, virus infection, or metabolic stress. During apoptosis, caspases cleave K18 and K19 at conserved aspartates (human K18/K19: (235) Val-Glu Val-Asp(?) ) and K18 at a unique aspartate (human K18: (394) Asp-Ala-Leu-Asp(?) ), with the latter exposed epitope becoming recognized by the M30 antibody in blood and tissues. Additional K18-containing protein backbone epitopes are detected using the M6 and M5 (termed M65) antibodies. Intact K18 and its associated fragments, which are released into blood during apoptosis and necrosis in various diseases, have been analyzed by enzyme-linked immunosorbent assay using the M30/M65 antibodies or their signal ratios. Furthermore, M30/M65 levels have been used as diagnostic and prognostic biomarkers in acute and chronic liver diseases, including nonalcoholic steatohepatitis and acute liver failure. Other keratin biomarkers include K8/K18/K19-related tissue polypeptide antigen, K18 related tissue polypeptide-specific antigen, and K19-related CYFRA-21-1, which have been evaluated mostly in patients with epithelial tumors. CONCLUSION: Keratins and their fragments are released into blood during liver and other epithelial tissue injury. The epithelial specificity of K18/K19, epitope unmasking upon caspase digestion, keratin abundance, and relative keratin stability render them useful biomarkers for hepatocyte and cholangiocyte apoptosis and necrosis. However, the precise biochemical nature and release mechanism of circulating keratins remain unknown. (Hepatology 2016;64:966-976). PMID- 26853545 TI - Prevalent hyperglycemia in older obese population and age-dependent convergence of obese indices: Results of a cross-sectional study of Japanese generations over the adult life span. AB - PURPOSE/AIM: An age-dependent decline has been observed in the association between obesity and type 2 diabetes, a major comorbidity of obesity, although the evidence is limited. Therefore, we investigated the association and the plausible underlying mechanism in a large epidemiological study. MATERIALS AND METHODS: We examined the association between the degree of obesity and hyperglycemia in five age groups (20-39, 40-49, 50-59, 60-69, and 70-85 years) in a cross-sectional study of 78,776 apparently healthy Japanese men and women who underwent a checkup in 2012. Hyperglycemia was defined as glycosylated hemoglobin (HbA1c) of >=5.7% and/or pharmacotherapy for diabetes. RESULTS: The incidence of hyperglycemia was three times higher in the 70-85-year-old group (62%) than in the 20-39-year-old group (20%) in obese individuals (body mass index [BMI] >= 27.0 kg/m(2)). However, the incidence was 12 times higher in reference-weight individuals (21.0 22.9 kg/m(2); 48% and 4%, respectively). As age increased, mean BMI and waist circumference approached certain non-obese ranges (22-24 kg/m(2) and 80-86 cm, respectively), even in hyperglycemic subjects. Logistic regression analysis revealed an age-dependent decline in the association between obesity and hyperglycemia, relative to that in reference-weight individuals. CONCLUSIONS: Our results confirmed the previously reported age-dependent decline in the association between obesity and hyperglycemia, although hyperglycemia was still prevalent in older obese subjects than in older reference-weight subjects. Therefore, the decline in the association may be accelerated due to an age dependent increase in the prevalence of hyperglycemia in reference-weight individuals. PMID- 26853546 TI - Assessing real-time sun protection decisions using audio diaries: feasibility and outcomes. PMID- 26853548 TI - Tongue displacement and durational characteristics of normal and disordered Brazilian Portuguese liquids. AB - The goal of the present study was to characterize normal and disordered Brazilian Portuguese liquids. The research hypotheses were that disordered liquid sounds would be characterized by (1) longer syllable and segment durations, (2) larger and more undifferentiated displacement of the tongue and (3) that the speech errors would show sub-phonemic differences depending on the target sound. The participants of this study were 11 children with phonological disorders and 9 control participants matched for age and educational background. The children's tongue movement in the sagittal plane was recorded with ultrasound. The speech stimuli consisted of 3 repetitions of 5 words representing the four Brazilian Portuguese liquids /l/, /y/, /r/ and /R/ in the context of the vowel /a/. A panel of four listeners transcribed each of the productions and classified them as correct or incorrect. The outcome measures were based on duration (syllable duration, ratio L/V) and tongue displacement (percentage average displacement, anterior displacement, posterior displacement). Based on mixed model analyses of variance, the first research hypothesis was confirmed for the /l/ and /r/ targets, but not for the /R/ and /y/ targets. The second hypothesis was partially confirmed. The third hypothesis was confirmed. The research serves to illustrate the effects of phonological disorder on the phonetic realisation of Brazilian Portuguese liquid sounds. PMID- 26853547 TI - Model predictions of features in microsaccade-related neural responses in a feedforward network with short-term synaptic depression. AB - Recently, the significant microsaccade-induced neural responses have been extensively observed in experiments. To explore the underlying mechanisms of the observed neural responses, a feedforward network model with short-term synaptic depression has been proposed [Yuan, W.-J., Dimigen, O., Sommer, W. and Zhou, C. Front. Comput. Neurosci. 7, 47 (2013)]. The depression model not only gave an explanation for microsaccades in counteracting visual fading, but also successfully reproduced several microsaccade-related features in experimental findings. These results strongly suggest that, the depression model is very useful to investigate microsaccade-related neural responses. In this paper, by using the model, we extensively study and predict the dependance of microsaccade related neural responses on several key parameters, which could be tuned in experiments. Particularly, we provide a significant prediction that microsaccade related neural response also complies with the property "sharper is better" observed in many contexts in neuroscience. Importantly, the property exhibits a power-law relationship between the width of input signal and the responsive effectiveness, which is robust against many parameters in the model. By using mean field theory, we analytically investigate the robust power-law property. Our predictions would give theoretical guidance for further experimental investigations of the functional role of microsaccades in visual information processing. PMID- 26853549 TI - Calcified band causing flow obstruction in the left anterior descending artery. PMID- 26853551 TI - Stem Cell Factor and Interleukin-31 Expression: Association with IgE among Egyptian Patients with Atopic and Nonatopic Bronchial Asthma. AB - Bronchial asthma is a chronic inflammatory disorder which remains a significant cause of morbidity. Recently, it has been reported that the stem cell factor (SCF) and interleukin-31 (IL-31) may play a major role in bronchial asthma. The aim of the current study was to study the association of the stem cell factor and interleukin-31 expression with serum immunoglobulin E among Egyptian patients with atopic and nonatopic bronchial asthma. After measuring serum IgE using total enzyme linked immunosorbent assay (ELISA), Ribonucleic acid (RNA) was isolated to determine gene expression of SCF and IL-31 by real-time polymerase chain reaction (PCR). The levels of SCF mRNAs in atopic asthmatic patients' PBMCs were significantly higher than those in controls (p = 0.0001**) and nonatopic asthmatics (p = 0.0001**). There was a high statistical significant difference also with regard to IL-31 between atopic asthmatics and controls (p = 0.0001**) and between them and nonatopic patients (p = 0.014*). There was a strong significant direct correlation between SCF, IL-31 (r = 0.827 and p = 0.0001**) and between both of them and IgE in asthmatics (r = 0.543 and p = 0.0001**) (r = 0.443 and p = 0.0001**), respectively. A direct correlation between SCF, IL-31 and FEV-1/ FVC %, CRP and wheezing existed. These findings suggest that both SCF and IL-31 play an important role in mediating inflammation and enhancing severity of atopic asthma. Augmented inhaled glucocorticoid therapy was associated with significant reductions in SCF and IL-31 mRNA expression as well as improvements in lung function, symptom scores and bronchial hyperresponsiveness to methacholine (PD20) in atopic and nonatopic asthmatics. PMID- 26853550 TI - Mechanical evidence that Australopithecus sediba was limited in its ability to eat hard foods. AB - Australopithecus sediba has been hypothesized to be a close relative of the genus Homo. Here we show that MH1, the type specimen of A. sediba, was not optimized to produce high molar bite force and appears to have been limited in its ability to consume foods that were mechanically challenging to eat. Dental microwear data have previously been interpreted as indicating that A. sediba consumed hard foods, so our findings illustrate that mechanical data are essential if one aims to reconstruct a relatively complete picture of feeding adaptations in extinct hominins. An implication of our study is that the key to understanding the origin of Homo lies in understanding how environmental changes disrupted gracile australopith niches. Resulting selection pressures led to changes in diet and dietary adaption that set the stage for the emergence of our genus. PMID- 26853552 TI - In vivo bone regeneration on titanium devices using serum-free grown adipose derived stem cells, in a sheep femur model. AB - AIM: The aim of this study was to investigate the capacity of adipose-derived stem cells (ADSC), grown in serum-free conditions, to regenerate bone around titanium discs with different titanium surfaces. MATERIAL AND METHODS: Ovine ADSC (oADSC) were isolated from seven sheep and cultured using serum-free and osteogenic conditions. Prior to in vivo testing, the growth and osteogenic behaviour of these cells were analysed in vitro using cell proliferation and extracellular matrix mineralisation assays. The bone regenerative capacity of autologous oADSC was evaluated in vivo on titanium discs in a sheep femur epicondyle model. Machined (MTi) and alumina-blasted (ABTi) titanium discs were used. Bone regeneration within the defects was evaluated after 1 month using histology and histomorphometry. PKH26 cell-tracking dye was used to verify the persistence of oADSC in the surgical wound. RESULTS: oADSC sourced from five of seven sheep differentiated into osteoblast-like cells. Cellular proliferation was reduced only for osteogenically induced oADSC (oOS-ADSC) grown on ABTi, compared to non-induced oADSC grown on ABTi and tissue culture polystyrene (P = 0.03 and 0.02 respectively). There was no significant difference for in vitro mineralisation assays comparing oADSC with oOS-ADSC, regardless of implant surface type. oADSC labelled with PKH26 were detected 1 month after surgery within the defect. There was no difference in bone regeneration between the bone defects treated with oADSC vs. just blood clot. CONCLUSION: After 1-month healing, the use of autologous oADSC did not improve bone regeneration in defects containing titanium devices with different surfaces. PMID- 26853554 TI - Angio-Vasculogenic Properties of Endothelial-Induced Mesenchymal Stem Cells Derived From Human Adipose Tissue. AB - BACKGROUND: Although stem cells have been regarded as a promising therapeutic option, the marginal therapeutic effects of stem cells are limitations that must be overcome for the development of effective cell therapy. This study sought to identify the angio-vasculogenic properties of endothelial differentiated mesenchymal stem cells (MSCs) and to determine whether these cells are effective for vascular repair. METHODS AND RESULTS: Adipose MSCs were cultured for 10 days under endothelial cell (EC) culture conditions. These endothelial cell differentiated adipose MSCs (EA) and undifferentiated adipose MSCs (UA) were characterized via angiogenesis and adhesion assays. These cells were transplanted into a hindlimb ischemia (HLI) model to determine therapeutic effects and their underlying mechanisms. EA displayed low adhesion and angiogenic properties in vitro compared with UA. When implanted into mouse HLI models, EA exhibited the decreased recovery of blood perfusion in limb ischemia than uncultured UA. Histology data showed that injected EA exhibited lower retention, angiogenic cytokine levels, and neovascularization in vivo than did UA. Short-term differentiated EA display less cell engraftment and angio-vasculogenic potential, and are less effective for peripheral vascular repair than UA. CONCLUSIONS: EC differentiation of MSCs may not present an effective strategy for the promotion of therapeutic neovascularization. PMID- 26853553 TI - H19 activates Wnt signaling and promotes osteoblast differentiation by functioning as a competing endogenous RNA. AB - Bone homeostasis is tightly orchestrated and maintained by the balance between osteoblasts and osteoclasts. Recent studies have greatly expanded our understanding of the molecular mechanisms of cellular differentiation. However, the functional roles of non-coding RNAs particularly lncRNAs in remodeling bone architecture remain elusive. In our study, lncRNA H19 was found to be upregulated during osteogenesis in hMSCs. Stable expression of H19 significantly accelerated in vivo and in vitro osteoblast differentiation. Meanwhile, by using bioinformatic investigations and RIP assays combined with luciferase reporter assays, we demonstrated that H19 functioned as an miRNA sponge for miR-141 and miR-22, both of which were negative regulators of osteogenesis and Wnt/beta catenin pathway. Further investigations revealed that H19 antagonized the functions of these two miRNAs and led to de-repression of their shared target gene beta-catenin, which eventually activated Wnt/beta-catenin pathway and hence potentiated osteogenesis. In addition, we also identified a novel regulatory feedback loop between H19 and its encoded miR-675-5p. And miR-675-5p was found to directly target H19 and counteracted osteoblast differentiation. To sum up, these observations indicate that the lncRNA H19 modulates Wnt/beta-catenin pathway by acting as a competing endogenous RNA, which may shed light on the functional role of lncRNAs in coordinating osteogenesis. PMID- 26853555 TI - From Left Ventricular Hypertrophy to Dysfunction and Failure. AB - Left ventricular hypertrophy (LVH) is growth in left ventricular mass caused by increased cardiomyocyte size. LVH can be a physiological adaptation to strenuous physical exercise, as in athletes, or it can be a pathological condition, which is either genetic or secondary to LV overload. Physiological LVH is usually benign and regresses upon reduction/cessation of physical activity. Pathological LVH is a compensatory phenomenon, which eventually may become maladaptive and evolve towards progressive LV dysfunction and heart failure (HF). Both interstitial and replacement fibrosis play a major role in the progressive decompensation of the hypertrophied LV. Coronary microvascular dysfunction (CMD) and myocardial ischemia, which have been demonstrated in most forms of pathological LVH, have an important pathogenetic role in the formation of replacement fibrosis and both contribute to the evolution towards LV dysfunction and HF. Noninvasive imaging allows detection of myocardial fibrosis and CMD, thus providing unique information for the stratification of patients with LVH. (Circ J 2016; 80: 555-564). PMID- 26853556 TI - Atrial Fibrillation and Heart Failure-- Identification of Patients at Risk. PMID- 26853558 TI - PrimerMapper: high throughput primer design and graphical assembly for PCR and SNP detection. AB - Primer design represents a widely employed gambit in diverse molecular applications including PCR, sequencing, and probe hybridization. Variations of PCR, including primer walking, allele-specific PCR, and nested PCR provide specialized validation and detection protocols for molecular analyses that often require screening large numbers of DNA fragments. In these cases, automated sequence retrieval and processing become important features, and furthermore, a graphic that provides the user with a visual guide to the distribution of designed primers across targets is most helpful in quickly ascertaining primer coverage. To this end, I describe here, PrimerMapper, which provides a comprehensive graphical user interface that designs robust primers from any number of inputted sequences while providing the user with both, graphical maps of primer distribution for each inputted sequence, and also a global assembled map of all inputted sequences with designed primers. PrimerMapper also enables the visualization of graphical maps within a browser and allows the user to draw new primers directly onto the webpage. Other features of PrimerMapper include allele-specific design features for SNP genotyping, a remote BLAST window to NCBI databases, and remote sequence retrieval from GenBank and dbSNP. PrimerMapper is hosted at GitHub and freely available without restriction. PMID- 26853559 TI - Bound Phenolics of Quinoa Seeds Released by Acid, Alkaline, and Enzymatic Treatments and Their Antioxidant and alpha-Glucosidase and Pancreatic Lipase Inhibitory Effects. AB - Unextractable phenolics from plant foods and their role in health benefits have become increasingly important. Meal residues of three quinoa seeds free of fat and extractable phenolics were subjected to acid, alkaline, and enzymatic hydrolyses. The total and individual phenolic compounds released were analyzed, and 19 phenolics, predominantly phenolic acids and several flavonoids, were identified. The concentration of bound phenolics was highest in black quinoa followed by red and white, regardless of the hydrolysis method. Higher phenolic contents also showed stronger antioxidant activities and inhibition of alpha glucosidase and pancreatic lipase activities. Carbohydrases, that is, pectinase, xylanase and feruloyl esterase, which effectively liberated bound phenolics are known to be secreted by colonic bacteria, suggesting potential antioxidant and anti-inflammatory effects by these compounds in the large intestine during colonic fermentation. These results can also be applied to treat foods high in bound phenolics to enhance bioaccessibility. PMID- 26853560 TI - Tumor suppressor properties of the splicing regulatory factor RBM10. AB - RBM10 is an RNA binding protein and alternative splicing regulator frequently mutated in lung adenocarcinomas. Recent results indicate that RBM10 inhibits proliferation of lung cancer cells by promoting skipping of exon 9 of the gene NUMB, a frequent alternative splicing change in lung cancer generating a negative regulator of Notch signaling. Complementing these observations, we show that knock down of RBM10 in human cancer cells enhances growth of mouse tumor xenografts, confirming that RBM10 acts as a tumor suppressor, while knock down of an oncogenic mutant version of RBM10 reduces xenograft tumor growth. A RBM10 mutation found in lung cancer cells, V354E, disrupts RBM10-mediated regulation of NUMB alternative splicing, inducing the cell proliferation-promoting isoform. We now show that 2 natural RBM10 isoforms that differ by the presence or absence of V354 in the second RNA Recognition Motif (RRM2), display similar regulatory effects on NUMB alternative splicing, suggesting that V354E actively disrupts RBM10 activity. Structural modeling localizes V354 in the outside surface of one alpha-helix opposite to the RNA binding surface of RBM10, and we show that the mutation does not compromise binding of the RRM2 domain to NUMB RNA regulatory sequences. We further show that other RBM10 mutations found in lung adenocarcinomas also compromise regulation of NUMB exon 9. Collectively, our previous and current results reveal that RBM10 is a tumor suppressor that represses Notch signaling and cell proliferation through the regulation of NUMB alternative splicing. PMID- 26853557 TI - Exercise, inflammation, and fatigue in cancer survivors. AB - Cancer-related fatigue significantly disrupts normal functioning and quality of life for a substantial portion of cancer survivors, and may persist for years following cancer treatment. While the causes of persistent fatigue among cancer survivors are not yet fully understood, accumulating evidence suggests that several pathways, including chronic inflammation, autonomic imbalance, HPA-axis dysfunction, and/or mitochondrial damage, could contribute towards the disruption of normal neuronal function and result in the symptom of cancer-related fatigue. Exercise training interventions have been shown to be some of the more successful treatment options to address cancer-related fatigue. In this review, we discuss the literature regarding the causes of persistent fatigue in cancer survivors and the mechanisms by which exercise may relieve this symptom. There is still much work to be done until the prescription of exercise becomes standard practice for cancer survivors. With improvements in the quality of studies, evidenced-based exercise interventions will allow exercise scientists and oncologists to work together to treat cancer-related fatigue. PMID- 26853562 TI - Impact of high CO2 on the geochemistry of the coralline algae Lithothamnion glaciale. AB - Coralline algae are a significant component of the benthic ecosystem. Their ability to withstand physical stresses in high energy environments relies on their skeletal structure which is composed of high Mg-calcite. High Mg-calcite is, however, the most soluble form of calcium carbonate and therefore potentially vulnerable to the change in carbonate chemistry resulting from the absorption of anthropogenic CO2 by the ocean. We examine the geochemistry of the cold water coralline alga Lithothamnion glaciale grown under predicted future (year 2050) high pCO2 (589 MUatm) using Electron microprobe and NanoSIMS analysis. In the natural and control material, higher Mg calcite forms clear concentric bands around the algal cells. As expected, summer growth has a higher Mg content compared to the winter growth. In contrast, under elevated CO2 no banding of Mg is recognisable and overall Mg concentrations are lower. This reduction in Mg in the carbonate undermines the accuracy of the Mg/Ca ratio as proxy for past temperatures in time intervals with significantly different carbonate chemistry. Fundamentally, the loss of Mg in the calcite may reduce elasticity thereby changing the structural properties, which may affect the ability of L. glaciale to efficiently function as a habitat former in the future ocean. PMID- 26853563 TI - Schaumann body identified on bronchial brushing in a patient with sarcoidosis. PMID- 26853561 TI - Transcription Factor RFX2 Is a Key Regulator of Mouse Spermiogenesis. AB - The regulatory factor X (RFX) family of transcription factors is crucial for ciliogenesis throughout evolution. In mice, Rfx1-4 are highly expressed in the testis where flagellated sperm are produced, but the functions of these factors in spermatogenesis remain unknown. Here, we report the production and characterization of the Rfx2 knockout mice. The male knockout mice were sterile due to the arrest of spermatogenesis at an early round spermatid step. The Rfx2 null round spermatids detached from the seminiferous tubules, forming large multinucleated giant cells that underwent apoptosis. In the mutants, formation of the flagellum was inhibited at its earliest stage. RNA-seq analysis identified a large number of cilia-related genes and testis-specific genes that were regulated by RFX2. Many of these genes were direct targets of RFX2, as revealed by chromatin immunoprecipitation-PCR assays. These findings indicate that RFX2 is a key regulator of the post-meiotic development of mouse spermatogenic cells. PMID- 26853564 TI - Editorial. PMID- 26853565 TI - 36th NATIONAL CONGRESS OF THE CZECH SOCIETY OF PLASTIC SURGERY WITH INTERNATIONAL PARTICIPATION. PMID- 26853584 TI - Dorsoradial forearm flap with silicone bone spacer in reconstruction of A combined THUMB injury - case report. AB - Osseous reconstruction of the thumb following traumatic bone loss can be approached through a variety of techniques. The use of a silicone spacer with secondary bone grafting is a valid therapeutic option. In case of combined injuries, simultaneous immediate reconstruction of missing soft tissues over the spacer by well-vascularised skin cover is essential. Dorsoradial forearm flap has recently been described as distally based cutaneous pedicled flap on the dorsoradial artery, a constant branch of the radial artery. A case of a 52-year old male patient with a combined injury of the thumb with bone loss of the proximal phalanx and with the loss of dorsal skin reconstructed primarily with bone silicon spacer and together with emergency dorsoradial forearm flap is reported together with a brief literature review. PMID- 26853585 TI - ZORA JANZEKOVIC (September 30, 1918 - March 17, 2015). PMID- 26853587 TI - Antiangiogenic therapy in oncology: current status and future directions. AB - Angiogenesis, the formation of new blood vessels from pre-existing vessels, has been validated as a target in several tumour types through randomised trials, incorporating vascular endothelial growth factor (VEGF) pathway inhibitors into the therapeutic armoury. Although some tumours such as renal cell carcinoma, ovarian and cervical cancers, and pancreatic neuroendocrine tumours are sensitive to these drugs, others such as prostate cancer, pancreatic adenocarcinoma, and melanoma are resistant. Even when drugs have yielded significant results, improvements in progression-free survival, and, in some cases, overall survival, are modest. Thus, a crucial issue in development of these drugs is the search for predictive biomarkers-tests that predict which patients will, and will not, benefit before initiation of therapy. Development of biomarkers is important because of the need to balance efficacy, toxicity, and cost. Novel combinations of these drugs with other antiangiogenics or other classes of drugs are being developed, and the appreciation that these drugs have immunomodulatory and other modes of action will lead to combination regimens that capitalise on these newly understood mechanisms. PMID- 26853589 TI - Dissolved organic carbon from the upper Rio Negro protects zebrafish (Danio rerio) against ionoregulatory disturbances caused by low pH exposure. AB - The so-called "blackwaters" of the Amazonian Rio Negro are rich in highly coloured dissolved organic carbon (DOC), but ion-poor and very acidic, conditions that would cause fatal ionoregulatory failure in most fish. However these blackwaters support 8% of the world's ichthyofauna. We tested the hypothesis that native DOC provides protection against ionoregulatory dysfunction in this extreme environment. DOCs were isolated by reverse-osmosis from two Rio Negro sites. Physico-chemical characterization clearly indicated a terrigenous origin, with a high proportion of hydroxyl and phenolic sites, high chemical reactivity to protons, and unusual proteinaceous fluorescence. When tested using zebrafish (a model organism), Rio Negro DOC provided almost perfect protection against ionoregulatory disturbances associated with acute exposure to pH 4.0 in ion-poor water. DOC reduced diffusive losses of Na(+) and Cl(-), and promoted a remarkable stimulation of Na(+) uptake that otherwise would have been completely inhibited. Additionally, prior acclimation to DOC at neutral pH reduced rates of branchial Na(+) turnover, and provided similar protection against acid-induced ionoregulatory disturbances, even if the DOC was no longer present. These results reinforce the important roles that DOC molecules can play in the regulation of gill functions in freshwater fish, particularly in ion-poor, acidic blackwaters. PMID- 26853591 TI - An approach to analyzing environmental drivers to spatial variations in annual distribution of periphytic protozoa in coastal ecosystems. AB - The environmental drivers to the spatial variation in annual distribution were studied based on an annual dataset of periphytic protozoa using multivariate approaches. Samples were monthly collected at four stations within a pollution gradient in coastal waters of the Yellow Sea, northern China during a 1-year period. The second-stage (2STAGE) analyses showed that the internal patterns of the annual distribution were changed along the pollution gradient in terms of abundance. The dominant species represented different succession dynamics among four sampling stations during a 1-year cycle. Best matching analysis demonstrated that the spatial variations in annual distribution of the protozoa were significantly correlated with ammonium nitrogen (NH4-N), alone or in combination with salinity and dissolved oxygen (DO). Based on the results, we suggest that the nutrients, salinity and DO may be the main drivers to shape the spatial variations in annual distribution of periphytic protozoa. PMID- 26853590 TI - Immunization with a 22-kDa outer membrane protein elicits protective immunity to multidrug-resistant Acinetobacter baumannii. AB - A. baumannii infections are becoming more and more serious health issues with rapid emerging of multidrug and extremely drug resistant strains, and therefore, there is an urgent need for the development of nonantibiotic-based intervention strategies. This study aimed at identifying whether an outer membrane protein with molecular weight of about 22 kDa (Omp22) holds the potentials to be an efficient vaccine candidate and combat A. baumannii infection. Omp22 which has a molecule length of 217 amino acids kept more than 95% conservation in totally 851 reported A. baumannii strains. Recombinant Omp22 efficiently elicited high titers of specific IgG in mice. Both active and passive immunizations of Omp22 increased the survival rates of mice, suppressed the bacterial burdens in the organs and peripheral blood, and reduced the levels of serum inflammatory cytokines and chemokines. Opsonophagocytosis assays showed in vitro that Omp22 antiserum had highly efficient bactericidal activities on clonally distinct clinical A. baumannii isolates, which were partly complements-dependent and opsonophagocytic killing effects. Additionally, administration with as high as 500 MUg of Omp22 didn't cause obvious pathological changes in mice. In conclusion, Omp22 is a novel conserved and probably safe antigen for developing effective vaccines or antisera to control A. baumannii infections. PMID- 26853592 TI - Accumulation patterns of lipophilic organic contaminants in surface sediments and in economic important mussel and fish species from Jakarta Bay, Indonesia. AB - Non-target screening analyses were conducted in order to identify a wide range of organic contaminants in sediment and animal tissue samples from Jakarta Bay. High concentrations of di-iso-propylnaphthalenes (DIPNs), linear alkylbenzenes (LABs) and polycyclic aromatic hydrocarbons (PAHs) were detected in all samples, whereas phenylmethoxynaphthalene (PMN), DDT and DDT metabolites (DDX) were detected at lower concentrations. In order to evaluate the uptake and accumulation by economic important mussel (Perna viridis) and fish species, contaminant patterns of DIPNs, LABs and PAHs in different compartments were compared. Different patterns of these contaminant groups were found in sediment and animal tissue samples, suggesting compound-specific accumulation and metabolism processes. Significantly higher concentrations of these three contaminant groups in mussel tissue as compared to fish tissue from Jakarta Bay were found. Because P. viridis is an important aquaculture species in Asia, this result is relevant for food safety. PMID- 26853593 TI - Bioavailable metals in tourist beaches of Richards Bay, Kwazulu-Natal, South Africa. AB - Acid Leachable Trace Metal (ALTMs) concentrations in tourist beaches of Richards Bay, Kwazulu-Natal, South Africa were assessed. 53 surface sediment samples were collected from five different beaches (Kwambonambi Long Beach; Nhlabane Beach; Five Mile Beach; Alkanstrand Beach and Port Durnford Beach). The results of ALTMs (Fe, Mn, Cr, Cu, Ni, Co, Pb, Cd, Zn, As, Hg) suggest that they are enriched naturally and with some local industrial sources for (avg. in MUgg(-1)) Fe (3530 7219), Mn (46-107.11), Cd (0.43-1.00) and Zn (48-103.98). Statistical results indicate that metal concentrations were from natural origin attributed to leaching, weathering process and industrial sources. Comparative studies of metal concentrations with sediment quality guidelines and ecotoxicological values indicate that there is no adverse biological effect. Enrichment factor and geoaccumulation indices results indicate moderate enhancement of Fe (Igeo class 1 in FMB), Cd (EF>50; Igeo classes 2-4) and Zn (Igeo classes 1 & 2). PMID- 26853594 TI - The Soil-Borne Supremacy. AB - The rhizosphere microbiome plays an important role in plant growth, nutrition and health. Recent research unearthed that plant genotype-dependent navigation of microbial community composition in the rhizosphere is associated with fitness consequences for the host plant, providing great promise for breeding soil-borne supremacy traits into future crops. PMID- 26853595 TI - Unlocking the Secrets of the Rhizosphere. PMID- 26853596 TI - Bioactivity of Hybrid Polymeric Magnetic Nanoparticles and Their Applications in Drug Delivery. AB - BACKGROUND: Engineered magnetic nanoparticles (MNPs) possess unique properties and hold great potential in biomedicine and clinical applications. With their magnetic properties and their ability to work at cellular and molecular level, MNP have been applied both in-vitro and in-vivo in targeted drug delivery and imaging. Focusing on Iron Oxide Superparamagnetic nanoparticles (SPIONs), this paper elaborates on the recent advances in development of hybrid polymeric magnetic nanoparticles. Their main applications in drug delivery include Chemotherapeutics, Hyperthermia treatment, Radio-therapeutics, Gene delivary, and Biotheraputics. Physiochemical properties such as size, shape, surface and magnetic properties are key factors in determining their behavior. Additionally tailoring SPIONs surface is often vital for desired cell targetting and improved efficiency. Polymer coating is specifically reviewed with brief discussion of SPIONs administration routes. Commonly used drug release models for describing release mechanisms and the nanotoxicity aspects are also discussed. METHODS: This review focus on superparamagnetic nanoparticles coated with different types of polymers starting with the key physiochemical features that dominate their behavior. The importance of surface modification is addressed. Subsequently, the major classes of polymer modified iron oxide nanoparticles is demonstrated according to their clinical use and application. Clinically approved nanoparticles are then addressed and the different routes of administration are mentioned. Lastly, mathematical models of drug release profile of the common used nanoparticles are addressed. RESULTS: MNPs emerging in recent medicine are remarkable for both imaging and therapeutics, particularly, as drug carriers for their great potential in targeted delivery and cancer treatment. Targeting ability and biocompatibility can be improved though surface coating which provides a mean to alter the surface features including physical characteristics and chemical functionality. The use of biocompatible polymers can prevent aggregation, increase colloidal stability, evades nanoparticles uptake by RES, and can provide a surface for conjugation of targeting ligands such as peptide and biomolecules with high affinity to target cells. CONCLUSION: Great efforts to bring MNPs from lab testing stage to clinic are needed to understand their physicochemical properties and how they behave in vivo, which resulted in few of them to exist in the market today. Although magnetic nanoparticles have not yet fully reached their optimal safety and efficiency due to the challenges they face in vivo, their shortcomings can be overcome through improvement of magnetictargeted carrier by pre-clinical trials and continuous studies. PMID- 26853597 TI - Complex rehabilitation and the clinical condition of working rheumatoid arthritis patients: does cryotherapy always overtop traditional rehabilitation? AB - AIM: Rehabilitation slows the progress of rheumatoid arthritis (RA) and prevents progression of disability. This study aimed to compare the impact of two rehabilitation programmes on pain, disease activity, locomotor function, global health and work ability forecast in RA patients. MATERIALS AND METHODS: Sixty four employed women aged 24-65 years participated in the study. All patients underwent individual and instrumental kinesiotherapy. Thirty-two patients underwent cryogenic chamber therapy and local cryotherapy as well as non-weight bearing, instrumental and individual kinesiotherapy. The remaining 32 patients received traditional rehabilitation in the form of electromagnetic and instrumental therapy, individual and pool-based non-weight-bearing kinesiotherapy. Rehabilitation lasted 3 weeks. Patients were examined three times: prior to rehabilitation, after 3 weeks of therapy and 3 months after completion of rehabilitation. The following study instruments were used: to assess disease activity: DAS-28; functional impairment: HAQ-DI; pain severity: VAS; patients' overall well-being: a scale from 0 to 100 (Global Health Index); and patients' own prognosis of fitness for work: the 6th question from Work Ability Index (WAI). Statistical analysis of data was performed using the STATISTICA 8.0 package. Mixed-design two-way analysis of variance was used for hypothesis testing. RESULTS: All patients improved after rehabilitation. The group of patients those who underwent cryotherapy had improved DAS-28, HAQ-DI, VAS and global health scores immediately following the 3-week rehabilitation programme (p < 0.001, p = 0.001, p = 0.007 and p < 0.001, respectively), as well as at the 3-month follow-up (p < 0.001, p < 0.001, p = 0.009 and p < 0.001, respectively). Rehabilitation using cryotherapy resulted in greater improvement in disease activity DAS-28 [F(2,105) = 5.700; p = 0.007; eta(2) = 0.084] and HAQ DI locomotor function scores [F(2,109) = 6.771; p = 0.003; eta(2) = 0.098] compared to traditional rehabilitation. The impact of both forms of rehabilitation on patients' own prognosis of work ability in the next 2 years was not significant. Results of patients who underwent traditional approach showed decreased disease activity following the initial 3-week period; however, this improvement did not sustain to the end of follow-up, 3 months later. CONCLUSIONS: Complex rehabilitation in RA has a positive effect on patients' clinical condition. The rehabilitation programme that includes cryotherapy overtops traditional rehabilitation, particularly as regards improvement in locomotor function, disease activity and sustaining willingness to continue working and exerts long-lasting effect. IMPLICATIONS FOR REHABILITATION: Rehabilitation using cryotherapy is more effective in improving locomotor function, decreasing disease activity and sustaining willingness to continue working compared to traditional rehabilitation. Rehabilitation using cryotherapy significantly reduces the intensity of pain experienced by patients with RA, and this positive effect is maintained at 3 months post-rehabilitation. Complex rehabilitation, particularly treatment using cryotherapy, improves patients' subjective assessment of their overall well-being and perception of their disease. Complex rehabilitation in rheumatoid arthritis has a positive effect on patients' clinical condition. PMID- 26853598 TI - Reply by the Authors. PMID- 26853599 TI - Violation of eating expectancies does not reduce conditioned desires for chocolate. AB - Although eating desires can be easily learned, their extinction appears more difficult. The present two-session study aimed to investigate the role of eating expectancies in the short and longer-term extinction of eating desires. In addition, the relationship between eating desires and conditioned evaluations was examined to test whether they might share a similar mechanism. It was hypothesized that the short-term extinction of eating desires would be more successful after the disconfirmation of eating expectancies (instructed extinction or IE), while resulting in worse longer-term extinction because omission of the food reward during extinction is not surprising. In contrast to the hypotheses, it was found that IE had no effect on the short-term and longer term extinction of eating desires. Eating desires correlated with conditioned evaluations only to some extent. It is concluded that eating expectancies do not mediate the short-term extinction of conditioned eating desires. In addition, their longer-term extinction does not appear to be facilitated by a greater violation of eating expectancies. This suggests that it might not be necessary to focus on expectancy violation in cue exposure therapy to reduce eating desires. PMID- 26853600 TI - Sperm proteomics: potential impact on male infertility treatment. AB - Spermatozoa are unique cells that have highly compact DNA, motility (and hypermotility) patterns, a specific morphology, localized mitochondria and an apical acrosome. They are the end product of a dynamic process termed spermatogenesis. Sperm are therefore produced with specific proteins in order to effect different traits, such as the presence of cysteine-rich protamines in DNA, which effectively compacts DNA. Moreover, specific proteins are transferred during epididymal maturation and after ejaculation in order to render sperm capable of undergoing post-ejaculatory alterations, generally termed capacitation, which confers capacity to fertilize a mature oocyte. In addition, sperm exhibit several post-translational modifications, which are fundamental to their function, such as SUMOylation and ubiquitination. Discussed in this review is the current knowledge of the sperm proteome in terms of its composition and the function that these proteins determine, as well as their post-translational modifications and how these alter sperm functional integrity. Studies are emphasized that focus on shotgun proteomics--untargeted determination of the protein constituent of a cell in a given biological condition--and technologies currently applied toward that end are reviewed. PMID- 26853602 TI - Quantitative analysis of MRI-guided attenuation correction techniques in time-of flight brain PET/MRI. AB - PURPOSE: In quantitative PET/MR imaging, attenuation correction (AC) of PET data is markedly challenged by the need of deriving accurate attenuation maps from MR images. A number of strategies have been developed for MRI-guided attenuation correction with different degrees of success. In this work, we compare the quantitative performance of three generic AC methods, including standard 3-class MR segmentation-based, advanced atlas-registration-based and emission-based approaches in the context of brain time-of-flight (TOF) PET/MRI. MATERIALS AND METHODS: Fourteen patients referred for diagnostic MRI and (18)F-FDG PET/CT brain scans were included in this comparative study. For each study, PET images were reconstructed using four different attenuation maps derived from CT-based AC (CTAC) serving as reference, standard 3-class MR-segmentation, atlas-registration and emission-based AC methods. To generate 3-class attenuation maps, T1-weighted MRI images were segmented into background air, fat and soft-tissue classes followed by assignment of constant linear attenuation coefficients of 0, 0.0864 and 0.0975 cm(-1) to each class, respectively. A robust atlas-registration based AC method was developed for pseudo-CT generation using local weighted fusion of atlases based on their morphological similarity to target MR images. Our recently proposed MRI-guided maximum likelihood reconstruction of activity and attenuation (MLAA) algorithm was employed to estimate the attenuation map from TOF emission data. The performance of the different AC algorithms in terms of prediction of bones and quantification of PET tracer uptake was objectively evaluated with respect to reference CTAC maps and CTAC-PET images. RESULTS: Qualitative evaluation showed that the MLAA-AC method could sparsely estimate bones and accurately differentiate them from air cavities. It was found that the atlas-AC method can accurately predict bones with variable errors in defining air cavities. Quantitative assessment of bone extraction accuracy based on Dice similarity coefficient (DSC) showed that MLAA-AC and atlas-AC resulted in DSC mean values of 0.79 and 0.92, respectively, in all patients. The MLAA-AC and atlas-AC methods predicted mean linear attenuation coefficients of 0.107 and 0.134 cm(-1), respectively, for the skull compared to reference CTAC mean value of 0.138cm(-1). The evaluation of the relative change in tracer uptake within 32 distinct regions of the brain with respect to CTAC PET images showed that the 3 class MRAC, MLAA-AC and atlas-AC methods resulted in quantification errors of 16.2 +/- 3.6%, -13.3 +/- 3.3% and 1.0 +/- 3.4%, respectively. Linear regression and Bland-Altman concordance plots showed that both 3-class MRAC and MLAA-AC methods result in a significant systematic bias in PET tracer uptake, while the atlas-AC method results in a negligible bias. CONCLUSION: The standard 3-class MRAC method significantly underestimated cerebral PET tracer uptake. While current state-of-the-art MLAA-AC methods look promising, they were unable to noticeably reduce quantification errors in the context of brain imaging. Conversely, the proposed atlas-AC method provided the most accurate attenuation maps, and thus the lowest quantification bias. PMID- 26853601 TI - A khorasan wheat-based replacement diet improves risk profile of patients with type 2 diabetes mellitus (T2DM): a randomized crossover trial. AB - PURPOSES: The aim of the present study was to examine whether a replacement diet with products made with organic ancient khorasan wheat could provide additive protective effects in reducing glucose, insulin, lipid and inflammatory risk factors, and in restoring blood redox balance in type 2 diabetes mellitus (T2DM) patients compared to diet with product made with modern organic wheat. METHODS: We conducted a randomized, double-blinded crossover trial with two intervention phases on 21 T2DM patients (14 females, 7 males). The participants were assigned to consume products (bread, pasta, crackers and biscuits) made using semi-whole flour from organic wheat that was either from ancient khorasan wheat or modern control wheat for 8 weeks in a random order. An 8-week washout period was implemented between the interventions. Laboratory analyses were performed both at the beginning and at the end of each intervention phase. RESULTS: The metabolic risk profile improved only after the khorasan intervention period, as measured by a reduction in total and LDL cholesterol (mean reduction: -3.7 and -3.4 %, respectively), insulin (-16.3 %) and blood glucose (-9.1 %). Similarly, there was a significant reduction in circulating levels of reactive oxygen species (ROS), vascular endothelial growth factor (VEGF) and interleukin-1ra, and a significant increase of total antioxidant capacity (+6.3 %). No significant differences from baseline were noted after the modern control wheat intervention phase. The change (from pre- to post-intervention) between the two intervention arms was significantly different (p < 0.05) for total and LDL-c, insulin and HOMA index. CONCLUSIONS: A replacement diet with ancient khorasan wheat consumption provided additive protection in reducing total and LDL cholesterol, insulin, blood glucose, ROS production, and some inflammatory risk factors, which are all key factors warranting of control in secondary prevention of T2DM compared to a diet with products made with modern wheat. PMID- 26853603 TI - Assessment of exposure to pesticides during mixing/loading and spraying of tomatoes in the open field. AB - Some evidence of exposure-response of metolachlor and pendimethalin for lung cancer and an association of metribuzin with risk of glioma have been reported. The primary objectives in this study were to evaluate exposure and occupational risk during mixing/loading of pesticides and during their application to tomatoes cultivated in open fields. Sixteen farmers were sampled. Respiratory exposure was estimated by personal air sampling using fiberglass filters in a IOM device. Dermal exposure was assessed using skin pads and hand washing. Absorbed doses were estimated assuming 100% lung retention, and 50% or 10% skin absorption for metribuzin, and pendimethalin and metolachlor, respectively. The three pesticides were quantified by gas chromatography tandem mass spectrometry in all matrices. Metolachlor was used as a tracer of contamination of clothes and tractors unrelated to the exposure monitored. Respiratory exposure to metribuzin, used in granular form, was on average more than one order of magnitude higher than exposure to pendimethalin, used in the form of microencapsulated liquid. The actual doses were 0.067-8.08 ug/kg bw, 0.420-12.6 ug/kg bw, and 0.003-0.877 ug/kg bw for pendimethalin, metribuzin, and metolachlor, respectively. Dermal exposure was about 88% of the actual dose for metribuzin and more than 95%, for pendimethalin and metolachlor. For risk assessment, the total absorbed doses (sum of respiratory and skin absorbed doses) were compared with the AOEL for each compound. The actual and absorbed doses of the three pesticides were always lower than the acceptable operator exposure level (AOEL), which are reported to be 234 ug/kg bw, 20 ug/kg bw, and 150 ug/kg bw for pendimethalin, metribuzin, and metolachlor, respectively. In any case, personal protective equipment and spraying devices should be chosen with care to minimize exposure. PMID- 26853604 TI - Failure Is the New Success. PMID- 26853605 TI - Systematically Identified Failure Is the Route to a Successful Health System. AB - Although we have a systematic approach to innovation and evaluation (and scale up) for treatments, medical technologies and diagnostic tests in healthcare, we have no equivalent for service delivery innovations. Service delivery innovation is common but frequently goes unevaluated, leading to less systematic decisions about which innovations are scaled up and which ones are not. The absence of a formal evaluation system for service delivery innovation means that there is no objective standard for evaluating an innovation's success or failure, and thus no way to decide whether it should be scaled up, adapted and retested, or not scaled up at all. This results in "bad failure" - the scale-up of innovations that are untested, and the failure to scale-up other innovations that might have been effective but no one measured their effectiveness in a systematic way. PMID- 26853606 TI - Innovation in Healthcare Delivery: Commentary on an Evolutionary Approach. AB - Zwarenstein (2015) proposes a novel approach to healthcare innovation that parallels biological evolution, based on stimulation and reward of multiple small competing innovation projects conducted in the field by decentralized teams. Projects would be designed with explicit outcome targets and results would be widely disseminated and publicly available. More successful projects would be grown and spread. Critical to the model is accepting and reporting failure as well as success, for the benefit of future project design. Examining biological evolution for lessons for healthcare delivery innovation illuminates the need for diversity among healthcare systems to achieve optimum application of best practice interventions across jurisdictions with differing population, provider and facility characteristics. However, careful coordination will be needed to achieve the balance between diversity and harmony across jurisdictions necessary for effective governance and interaction. There are important methodological issues to be addressed to reduce the uncertainty inherent in comparisons of results among discrete innovation projects, especially when observed improvements over the baseline are modest. As well as evolutionary improvement in healthcare outcomes, the model should progressively increase decentralized capacity and expertise in innovation processes. PMID- 26853607 TI - Care, Attention and Making Tough Choices: Learning from Failure Means Weeding the Garden. AB - Like ecosystems in nature, healthcare systems are complex, interdependent systems. Does that mean they should be left to the forces of slower, evolutionary transformation? Given the pressures and expectations on public healthcare, the more deliberate hand of a gardener may be needed to "weed out" programs that are no longer fruitful in solving current issues. Taking such a discerning view of health system programs would mean re-examining attitudes about failure. Just as harvested plants provide compost that feeds the garden, knowledge gained from failure can strengthen healthcare. A public environment that favours "success stories" means other system participants don't get the benefit of the knowledge that can be gleaned from failure. Scientific disciplines advance knowledge by studying failed experiments. Health leaders must do the same. Even programs deemed "success stories" have likely failed in some ways, experience that should be shared as transparently and widely as the successes. Both notable successes and valiant failures can be equally valuable in designing health system programs that meet the needs of all patients. PMID- 26853608 TI - #FAIL: Defining, Understanding and Owning Our Failures. AB - Despite our best efforts to reform the healthcare system, significant challenges remain. To some extent, our progress is being hampered because of our hesitation to learn from past mistakes. In his article "Systematically Identified Failure Is the Route to a Successful Health System", Zwarenstein (2015) argues that we must right this wrong and begin to systematically identify, acknowledge and learn from failure if we want to make true progress. This commentary outlines some key steps that must be taken to help us move past failure and apply lessons to future healthcare reforms. To achieve this end state we propose adopting a disciplined approach that includes clearly defining policy goals, stratifying failures into categories to help facilitate learning and encouraging leaders to acknowledge and learn from failure. PMID- 26853609 TI - Learning about Failure from Successful Ecosystems. AB - The evolutionary model of competitive selection is hard to translate in healthcare where current culture, incentives and policies often lead to a failure to check if something works and act on the results. This is particularly problematic in areas of high uncertainty (and corresponding high risk of failure for any proposed strategy), like the care of people with complex needs. We look to the software sector as an example of a human ecosystem experiencing an explosion of diversity that facilitates participation of people from varied backgrounds and has strong selection processes and approaches to manage uncertainty. Key lessons from this sector include facilitating failure through rapid tests with ready alternatives, support for people (not just ideas) so they can try different approaches and a system-level portfolio investment to account for high likelihood of failure of any given project. A successful ecosystem in healthcare would not only select proven strategies, but promote collaboration among innovators so that there is cumulative system learning as opposed to personal empire building. Given the major fiscal, social and demographic challenges on the horizon, failure to search for novel solutions is a bigger risk than trying new things that might not work. PMID- 26853610 TI - Towards a Model of Stewardship and Accountability in Support of Innovation and "Good" Failure. AB - From an evolutionary perspective, failures of imagination and missed opportunities to learn from experimentation are as potentially harmful for the health system as failures of practice. The conundrum is encapsulated in the fact that while commentators are steadfast about the need on the part of the stewards of the health system to avoid any waste of public dollars, they are also insistent about the need for innovation. There is tension between these two imperatives that is often unrecognized: the pursuit of efficiency, narrowly defined, can crowd out the goal of innovation by insisting on the elimination of "good waste" (the costs of experimentation) as well as "bad waste" (the costs of inefficiency) (Potts 2009). This tension is mirrored in the two broad drivers of performance reporting in health systems: public accountability and quality improvement. Health organizations, predominantly funded by public funds, are necessarily accountable for the ways in which those funds are used and outcomes achieved. This paper reviews how accountability relationships should be re examined to create room for "good failure" and to ensure that system accountability does not become a barrier to performance improvement. PMID- 26853611 TI - Expand Focus to Larger Systems and Their Interdependence. AB - One potential issue with the invited essay's (Zwarenstein 2015) proposed evaluation approach is the Darwinian evolution of a system versus the evaluation/testing of a series of pinpoint solutions. There are many examples of bad research based on the influence of a single factor on a specific outcome. But in reality we need to look at larger systems and their interdependence. Quick testing is great as long as it can be tied to a larger ecosystem of causes and effects. PMID- 26853612 TI - The Strategic Value of Misconceiving Failure. AB - Canadian healthcare has learned a lot about failure; it is less clear that it has learned from it. Our system performs poorly on most indicators compared to our international peers. We continue to define failure narrowly and hence as a relatively rare phenomenon, which both comforts the status quo and douses the burning platform essential to large scale improvement. We cannot simultaneously tell ourselves that by and large Canadians are well-served by the system and at the same time call for transformation change. Success requires both that we recognize that the middle of the performance curve is riddled with failure, and that failure to produce achievable benefits is no less a failure than failure to avoid harm. The challenges are both conceptual and cognitive, and the first step is to determine how much truth we're prepared to face. PMID- 26853613 TI - Responses and Recommendations: Proposals for an Initiative to Improve Healthcare by Evaluating Innovation. AB - I appreciate the work that commentators have put into their responses and the insightful critiques and ideas they have contributed in response to my essay, "Systematically Identified Failure Is the Route to a Successful Health System" (2015). I begin with a brief summary of the essay and then provide my perspective on those comments. PMID- 26853615 TI - A contribution to the Torrey et al.'s "cat ownership inchildhood is a significant risk factor for later developing schizophrenia" study. PMID- 26853614 TI - Everyday discrimination and diurnal cortisol during adolescence. AB - PURPOSE: To examine the associations of the frequency and type of everyday discrimination with diurnal cortisol and whether those associations depend upon adolescents' ethnicity and gender. METHODS: Adolescents (N=292, Mage=16. 39years, SD=0.74; 58% female) reported the frequency of perceived everyday discrimination and whether they attributed that discrimination to race, gender, age, or height and weight. Five saliva samples were collected per day across 3days and assayed for cortisol. RESULTS: Higher frequency of everyday discrimination was associated with greater total daily cortisol output (area under the curve; AUC), lower wake and bedtime levels of cortisol, and less of a decline in cortisol across the day. These associations generally did not depend upon ethnicity or gender and attributions for the discrimination were not as consequential as the actual frequency of any type of unfair treatment. CONCLUSION: Everyday discrimination, regardless of its type, may contribute to heightened HPA activity among adolescents of different ethnic backgrounds and genders. PMID- 26853616 TI - Vitamin B12 and the risk of schizophrenia: A meta-analysis. PMID- 26853617 TI - The use of magnetic nanoparticles in cancer theranostics: Toward handheld diagnostic devices. AB - Magnetic nanoparticles are frequently used in a wide range of biomedical applications. In the first part of this review the most commonly used preparation and surface coating approaches of MNPs are briefly summarized including multifunctional hybrid particles. The second part gives a detailed overview of the use of MNPs in "traditional" biomedical applications related to cancer theranostics, like magnetic resonance imaging, drug delivery, hyperthermia and also their applicability in the next generation of point of care devices based on micro nuclear magnetic resonance and surface enhanced Raman spectroscopic detection technology that all can be routinely applied in everyday clinical practice. PMID- 26853618 TI - Barriers to outpatient stress testing follow-up for low-risk chest pain patients presenting to an ED chest pain unit. AB - INTRODUCTION: Outpatient stress testing (OST) after evaluation in the emergency department (ED) is an acceptable evaluation method for patients presenting to the ED with low-risk chest pain (CP). However, not all patients return for OST. Barriers to follow-up evaluation exist and are poorly understood. In this study, we examined the influence of demographic and social characteristics on OST compliance. METHODS: Data were collected on low-risk CP patients with scheduled OSTs. OST compliance was assessed and then analyzed for correlation with potential barriers including insurance type; age; sex; race; employment status; the distance the patient lived from the hospital; whether or not the patient had a primary care physician; whether or not the patient had a history of hypertension or diabetes; and whether or not the patient had a history of tobacco, alcohol, or illicit drug use. RESULTS: A total of 275 patients were enrolled over a 5-month period. These patients had an OST follow-up rate of 61.82% within 72hours of discharge from the ED. Patients with Medicaid were statistically less likely (odds ratio [OR], 0.439) to complete OST. Patients with commercial insurance (OR, 1.8225), who were employed (OR, 2.299), or who were retired (OR, 3.44) were more likely to complete OST. All of the other variables analyzed were not statistically significant factors in OST compliance. CONCLUSION: More than one-third of low-risk CP patients do not follow-up with scheduled OST. Of the variables analyzed, both employment status and insurance type were statistically significant and should be included in risk stratification strategies for OST. PMID- 26853619 TI - Histone deacetylase inhibitor pracinostat in doublet therapy: a unique strategy to improve therapeutic efficacy and to tackle herculean cancer chemoresistance. AB - Context Histone deacetylase inhibitors (HDACi) have shown promising results in neurodegeneration and cancer. Hydroxamate HDACi, including vorinostat, have shown encouraging results in haematological malignancies, but the poor pharmacokinetic of these inhibitors leads to insufficient tumour concentration limiting their application against solid malignancies. Objective This article deals with novel HDAC inhibitor pracinostat (SB939) and delineates its therapeutic role in solid and haematological malignancies. The article provides rigorous details about the underlying molecular mechanisms modulated by pracinostat to exert cytotoxic effect. The article further highlights the doublet therapy that may be used to tackle monotonous cancer chemoresistance. Methods Both old and the latest literature on pracinostat was retrieved from diverse sources, such as PubMed, Science Direct, Springer Link, general Google search using both pracinostat and SB939 keywords in various ways: after thorough evaluation the topic which can fulfil the current gap was chosen. Results Pracinostat shows potent anticancer activity against both solid and haematological malignancies compared to the FDA approved drug vorinostat. This marvellous inhibitor has better physicochemical, pharmaceutical and pharmacokinetic properties than the defined inhibitor vorinostat. Pracinostat has >100-fold more affinity towards HDACs compared to other zinc-dependent metalloenzymes and shows maximum efficacy when used in doublet therapy. Conclusion Pracinostat shows potent anticancer activity even against therapeutically challenging cancers when used in doublet therapy. However, the triplet combination studies of the defined inhibitor that may prove even more beneficial are still undone, emphasizing the desperate need of further research in the defined gap. PMID- 26853620 TI - Visual associations cued recall A Paradigm for Measuring Episodic Memory Decline in Alzheimer's Disease. AB - Repeated measurements of episodic memory are needed for monitoring amnestic mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). Most episodic memory tests may pose a challenge to patients, even when they are in the milder stages of the disease. This cross-sectional study compared floor effects of the Visual Association Test (VAT) and the Rey Auditory Verbal Learning Test (RAVLT) in healthy elderly controls and in patients with aMCI or AD (N = 125). A hierarchical multiple regression analysis was used to examine whether linear or quadratic trends best fitted the data of cognitive test performance across global cognitive impairment. Results showed that VAT total scores decreased linearly across the range of global cognitive impairment, whereas RAVLT total scores showed a quadratic trend, with total scores levelling off for 90% of aMCI patients and 94% of AD patients. We conclude that the VAT shows few if any floor effects in patients with aMCI and mild AD and is therefore a potentially promising cognitive test for monitoring episodic memory impairment. PMID- 26853622 TI - 3D ultrasound biomicroscopy for assessment of cartilage repair tissue: volumetric characterisation and correlation to established classification systems. AB - Objective and sensitive assessment of cartilage repair outcomes lacks suitable methods. This study investigated the feasibility of 3D ultrasound biomicroscopy (UBM) to quantify cartilage repair outcomes volumetrically and their correlation with established classification systems. 32 sheep underwent bilateral treatment of a focal cartilage defect. One or two years post-operatively the repair outcomes were assessed and scored macroscopically (Outerbridge, ICRS-CRA), by magnetic resonance imaging (MRI, MOCART), and histopathology (O'Driscoll, ICRS-I and ICRS-II). The UBM data were acquired after MRI and used to reconstruct the shape of the initial cartilage layer, enabling the estimation of the initial cartilage thickness and defect volume as well as volumetric parameters for defect filling, repair tissue, bone loss and bone overgrowth. The quantification of the repair outcomes revealed high variations in the initial thickness of the cartilage layer, indicating the need for cartilage thickness estimation before creating a defect. Furthermore, highly significant correlations were found for the defect filling estimated from UBM to the established classification systems. 3D visualisation of the repair regions showed highly variable morphology within single samples. This raises the question as to whether macroscopic, MRI and histopathological scoring provide sufficient reliability. The biases of the individual methods will be discussed within this context. UBM was shown to be a feasible tool to evaluate cartilage repair outcomes, whereby the most important objective parameter is the defect filling. Translation of UBM into arthroscopic or transcutaneous ultrasound examinations would allow non-destructive and objective follow-up of individual patients and better comparison between the results of clinical trials. PMID- 26853623 TI - Age-related changes in mesenchymal stem cells identified using a multi-omics approach. AB - Mesenchymal stem cells (MSC) are capable of multipotent differentiation into connective tissues and as such are an attractive source for autologous cell-based treatments for many clinical diseases and injuries. Ageing is associated with various altered cellular phenotypes coupled with a variety of transcriptional, epigenetic and translational changes. Furthermore, the regeneration potential of MSCs is reduced with increasing age and is correlated with changes in cellular functions. This study used a systems biology approach to investigate the transcriptomic (RNASeq), epigenetic (miRNASeq and DNA methylation) and protein alterations in ageing MSCs in order to understand the age-related functional and biological variations, which may affect their applications to regenerative medicine. We identified no change in expression of the cellular senescence markers. Alterations were evident at both the transcriptional and post transcriptional level in a number of transcription factors. There was enrichment in genes involved in developmental disorders at mRNA and differential methylated loci (DML) level. Alterations in energy metabolism were apparent at the DML and protein level. The microRNA miR-199b-5p, whose expression was reduced in old MSCs, had predicted gene targets involved in energy metabolism and cell survival. Additionally, enrichment of DML and proteins in cell survival was evident. Enrichment in metabolic processes was revealed at the protein level and in genes identified as undergoing alternate splicing. Overall, an altered phenotype in MSC ageing at a number of levels implicated roles for inflamm-ageing and mitochondrial ageing. Identified changes represent novel insights into the ageing process, with implications for stem cell therapies in older patients. PMID- 26853624 TI - Cold Stress Makes Escherichia coli Susceptible to Glycopeptide Antibiotics by Altering Outer Membrane Integrity. AB - A poor understanding of the mechanisms by which antibiotics traverse the outer membrane remains a considerable obstacle to the development of novel Gram negative antibiotics. Herein, we demonstrate that the Gram-negative bacterium Escherichia coli becomes susceptible to the narrow-spectrum antibiotic vancomycin during growth at low temperatures. Heterologous expression of an Enterococcus vanHBX vancomycin resistance cluster in E. coli confirmed that the mechanism of action was through inhibition of peptidoglycan biosynthesis. To understand the nature of vancomycin permeability, we screened for strains of E. coli that displayed resistance to vancomycin at low temperature. Surprisingly, we observed that mutations in outer membrane biosynthesis suppressed vancomycin activity. Subsequent chemical analysis of lipopolysaccharide from vancomycin-sensitive and resistant strains confirmed that suppression was correlated with truncations in the core oligosaccharide of lipopolysaccharide. These unexpected observations challenge the current understanding of outer membrane permeability, and provide new chemical insights into the susceptibility of E. coli to glycopeptide antibiotics. PMID- 26853621 TI - Dysregulation of splicing proteins in head and neck squamous cell carcinoma. AB - Signaling plays an important role in regulating all cellular pathways. Altered signaling is one of the hallmarks of cancers. Phosphoproteomics enables interrogation of kinase mediated signaling pathways in biological systems. In cancers, this approach can be utilized to identify aberrantly activated pathways that potentially drive proliferation and tumorigenesis. To identify signaling alterations in head and neck squamous cell carcinoma (HNSCC), we carried out proteomic and phosphoproteomic analysis of HNSCC cell lines using a combination of tandem mass tag (TMT) labeling approach and titanium dioxide-based enrichment. We identified 4,920 phosphosites corresponding to 2,212 proteins in six HNSCC cell lines compared to a normal oral cell line. Our data indicated significant enrichment of proteins associated with splicing. We observed hyperphosphorylation of SRSF protein kinase 2 (SRPK2) and its downstream substrates in HNSCC cell lines. SRPK2 is a splicing kinase, known to phosphorylate serine/arginine (SR) rich domain proteins and regulate splicing process in eukaryotes. Although genome wide studies have reported the contribution of alternative splicing events of several genes in the progression of cancer, the involvement of splicing kinases in HNSCC is not known. In this study, we studied the role of SRPK2 in HNSCC. Inhibition of SRPK2 resulted in significant decrease in colony forming and invasive ability in a panel of HNSCC cell lines. Our results indicate that phosphorylation of SRPK2 plays a crucial role in the regulation of splicing process in HNSCC and that splicing kinases can be developed as a new class of therapeutic target in HNSCC. PMID- 26853625 TI - Systematic Survey of Serine Hydrolase Activity in Mycobacterium tuberculosis Defines Changes Associated with Persistence. AB - The transition from replication to non-replication underlies much of Mycobacterium tuberculosis (Mtb) pathogenesis, as non- or slowly replicating Mtb are responsible for persistence and poor treatment outcomes. Therapeutic targeting of non-replicating populations is a priority for tuberculosis treatment, but few drug targets in non-replicating Mtb are currently known. Here, we directly measured the activity of the highly diverse and druggable serine hydrolases (SHs) during active replication and non-replication using activity based proteomics. We predict SH activity for 78 proteins, including 27 proteins with unknown function, and identify 37 SHs that remain active in the absence of replication, providing a set of candidate persistence targets. Non-replication was associated with major shifts in SH activity. These activity changes were largely independent of SH abundance, indicating extensive post-translational regulation of SHs. By probing a large cross-section of druggable Mtb enzyme space during replication and non-replication, we identify new SHs and suggest new persistence targets. PMID- 26853627 TI - Ancestral Protein Reconstruction Yields Insights into Adaptive Evolution of Binding Specificity in Solute-Binding Proteins. AB - The promiscuous functions of proteins are an important reservoir of functional novelty in protein evolution, but the molecular basis for binding promiscuity remains elusive. We used ancestral protein reconstruction to experimentally characterize evolutionary intermediates in the functional expansion of the polar amino acid-binding protein family, which has evolved to bind a variety of amino acids with high affinity and specificity. High-resolution crystal structures of an ancestral arginine-binding protein in complex with l-arginine and l-glutamine show that the promiscuous binding of l-glutamine is enabled by multi-scale conformational plasticity, water-mediated interactions, and selection of an alternative conformational substate productive for l-glutamine binding. Evolution of specialized glutamine-binding proteins from this ancestral protein was achieved by displacement of water molecules from the protein-ligand interface, reducing the entropic penalty associated with the promiscuous interaction. These results provide a structural and thermodynamic basis for the co-option of a promiscuous interaction in the evolution of binding specificity. PMID- 26853626 TI - Cell-Line Selectivity Improves the Predictive Power of Pharmacogenomic Analyses and Helps Identify NADPH as Biomarker for Ferroptosis Sensitivity. AB - Precision medicine in oncology requires not only identification of cancer associated mutations but also effective drugs for each cancer genotype, which is still a largely unsolved problem. One approach for the latter challenge has been large-scale testing of small molecules in genetically characterized cell lines. We hypothesized that compounds with high cell-line-selective lethality exhibited consistent results across such pharmacogenomic studies. We analyzed the compound sensitivity data of 6,259 lethal compounds from the NCI-60 project. A total of 2,565 cell-line-selective lethal compounds were identified and grouped into 18 clusters based on their median growth inhibitory GI50 profiles across the 60 cell lines, which were shown to represent distinct mechanisms of action. Further transcriptome analysis revealed a biomarker, NADPH abundance, for predicting sensitivity to ferroptosis-inducing compounds, which we experimentally validated. In summary, incorporating cell-line-selectivity filters improves the predictive power of pharmacogenomic analyses and enables discovery of biomarkers that predict the sensitivity of cells to specific cell death inducers. PMID- 26853628 TI - A multimodal approach to diabetic macular edema. AB - Diabetic retinopathy is a common complication of uncontrolled diabetes. A complication is diabetic macular edema, which is the leading cause of blindness in patients with diabetic retinopathy. Historically, management of these conditions was laser photocoagulation with regulation of blood pressure, blood sugar, and cholesterol. The initial studies demonstrated that this treatment regimen prevented further visual deterioration but did not improve visual acuity. Novel studies identifying the presence of vascular endothelial growth factor (VEGF) in the eye with accompanying elucidation of diabetic pathophysiology allowed for the development of alternative therapies, namely antibodies against VEGF and corticosteroids. These two therapies revolutionized the management of diabetic macular edema by not only preventing vision loss, but also improving overall vision. In this review, we outline the major breakthroughs and underlying thought processes of the paradigm shifts that have occurred in management of these conditions. Further, we present how the evolving role of anti-inflammatory and anti-VEGF therapies, in a combinatorial approach, may provide further permutations to optimize treatment. PMID- 26853629 TI - Smoking cessation and the incidence of impaired fasting glucose and type 2 diabetes mellitus. PMID- 26853630 TI - Impact of glycated LDL on endothelial nitric oxide synthase in vascular endothelial cells: involvement of transmembrane signaling and endoplasmic reticulum stress. AB - Cardiovascular diseases are the major cause of mortality in diabetes patients. Increased levels of glycated low density lipoprotein (glyLDL) are detected in diabetic patients. Endothelial nitric oxide synthase (eNOS) generates nitric oxide, which is responsible to endothelium-dependent vasodilation. The impact of glyLDL on the expression and activity of eNOS in vascular endothelial cells (EC) remains unknown. The present study investigated the effect of glyLDL on the levels of protein, mRNA and activity of eNOS in cultured human umbilical vein EC. The results demonstrated that incubation of EC with physiological concentrations of glyLDL significantly reduced the abundances of eNOS protein in EC with the maximal inhibition at 100MUg/ml for 24h. At the optimized condition, glyLDL decreased eNOS mRNA and reduced its activity in EC. Blocking antibody against the receptor for advanced glycation end products (RAGE) prevented glyLDL-induced downregulation of eNOS in EC. GlyLDL increased the translocation of H-Ras from cytoplasm to membrane in EC. Farnesyl-transferase inhibitor-276, an H-Ras antagonist, normalized glyLDL-induced downregulation of eNOS and prevented glyLDL induced upregulation of H-Ras in EC membrane. Treatment with 4-phenylbutyric acid, an endoplasmic reticulum (ER) stress antagonist, prevented glyLDL-induced eNOS downregulation in EC. The results suggest that diabetes-associated metabolic stress inhibits the production and activity of eNOA in cultured human vascular EC through the activation of RAGE/H-Ras mediated upstream signaling pathway. ER stress induced by glyLDL is possibly involved in eNOS downregulation. PMID- 26853631 TI - Photoinduced Electron Transfer in Organic Solar Cells. AB - Electron transfer (ET) is the key process in light-driven charge separation reactions in organic solar cells. The current review summarizes the progress in theoretical modelling of ET in these materials. First we give an account of ET, with a description originating from Marcus theory. We systematically go through all the relevant parameters and show how they depend on different material properties, and discuss the consequences such dependencies have for the performance of the devices. Finally, we present a set of visualization methods which have proven to be very useful in analyzing the elementary processes in absorption and charge separation events. Such visualization tools help us to understand the properties of the photochemical and photobiological systems in solar cells. PMID- 26853632 TI - A New ZrCuSiAs-Type Superconductor: ThFeAsN. AB - We report the first nitrogen-containing iron-pnictide superconductor ThFeAsN, which is synthesized by a solid-state reaction in an evacuated container. The compound crystallizes in a ZrCuSiAs-type structure with the space group P4/nmm and lattice parameters a = 4.0367(1) A and c = 8.5262(2) A at 300 K. The electrical resistivity and dc magnetic susceptibility measurements indicate superconductivity at 30 K for the nominally undoped ThFeAsN. PMID- 26853633 TI - Modulation of Cu(2-x)S Nanocrystal Plasmon Resonance through Reversible Photoinduced Electron Transfer. AB - Copper sulfide (Cu(2-x)S) nanocrystals with nonstoichiometric composition exhibit plasmon resonance in the near-infrared region. Compositional changes and varying electron density markedly affect the position and intensity of the plasmon resonance. We report a photochemically induced phenomenon of modulating the plasmon resonance in a controlled fashion. As photogenerated reduced methyl viologen radicals transfer electrons to Cu(2-x)S in inert solutions, we observe a decrease in localized surface plasmon resonance (LSPR) absorbance at 1160 nm. Upon exposure to air, the plasmon resonance band recovers as stored electrons are scavenged away by oxygen. This cycle of electron charge and discharge of Cu(2-x)S nanocrystals is reversible and can be repeated through photoirradiation in N2 saturated solution followed by exposure of the suspension to air. The spectroscopic studies that provide mechanistic insights into the reversible charging and discharging of plasmonic Cu(2-x)S are discussed. PMID- 26853634 TI - Purification and detoxification of petroleum refinery wastewater by electrocoagulation process. AB - The treatment of synthetic oily wastewater having the characteristics of a typical petroleum refinery wastewater (PRW) by electrocoagulation (EC) using iron and aluminum electrodes was conducted in an electrolytic reactor equipped with fluid recirculation. During the treatment, the emulsion stability was followed by the measurement of Zeta potential and particle sizes. Effects of some operating conditions such as electrodes material, current density and electrolysis time on removal efficiencies of turbidity, and chemical oxygen demand (COD) were investigated in detail. The PRW purification by the EC process was found to be the most effective using aluminum as the anode and cathode, current density of 60 A/m(2) and 30 min of electrolysis time. Under these conditions, the process efficiencies were 83.52% and 99.94%, respectively, for COD and turbidity removals which correspond to final values of 96 mg O2/L and 0.5 NTU. A moderate energy consumption (0.341 kWh) was needed to treat 1 m(3) of PRW. Besides, the ecotoxicity test proved that toxic substances presented in the PRW, and those inhibiting the germination growth of whet, were eliminated by the EC technique. PMID- 26853635 TI - An in vitro diagnosis of oral premalignant lesion using time-resolved fluorescence spectroscopy under UV excitation-a pilot study. AB - In spite of rapid advancement in cancer treatment, early diagnosis of cancer and medicable precursors are still the finest approach towards the assurance of patient lives and enhancement in the quality of their life. In this regard, the present study deals with the time-resolved fluorescence spectroscopy of normal and premalignant oral tissues under UV excitations (280nm and 310nm). The decay kinetics at 350nm emission of normal tissues exhibit higher fluorescence lifetime than that of premalignant tissues and subsequent statistical analysis shows that the data were statistically significant. Further, the decay kinetics at 450nm emission for normal and premalignant oral tissues was obtained. Subsequently, statistical analysis revealed that except fast component, rest of the component lifetimes and fractional amplitudes were not statistically significant. An attempt has also been made to explore the better statistical tool to discriminate premalignant tissues from normal ones at 350nm emission. Among stepwise linear discriminant analysis (SLDA) and receiver operator characteristics (ROC), the former discriminates premalignant from normal tissues with 86.7% specificity and 93.3% sensitivity. Hence, fluorescence lifetime spectroscopy at 350nm emission opens a new avenue for early detection of oral cancer. PMID- 26853636 TI - Sclerodermiform BCC treated with multiple PDT sessions. PMID- 26853637 TI - Synthesis of alpha-aminoboronic acids. AB - This review describes available methods for the preparation of alpha-aminoboronic acids in their racemic or in their enantiopure form. Both, highly stereoselective syntheses and asymmetric procedures leading to the stereocontrolled generation of alpha-aminoboronic acid derivatives are included. The preparation of acyclic, carbocyclic and azacyclic alpha-aminoboronic acid derivatives is covered. Within each section, the different synthetic approaches have been classified according to the key bond which is formed to complete the alpha-aminoboronic acid skeleton. PMID- 26853638 TI - Shunt malfunction mimicking a cystic tumour. AB - Shunt malfunction represents one of the most common problem to deal with in the daily neurosurgical practice. Among the variety of possible presentations, the cyst-like dilatation of the brain around the proximal catheter is one of the most rare and misleading type. The case of a boy with a 'tumour-like' proximal shunt malfunction is described and the pertinent literature is analysed. PMID- 26853639 TI - Crowdsourcing biologicals. PMID- 26853641 TI - New hope for patients with livedoid vasculopathy. PMID- 26853640 TI - Catheter-directed thrombolysis: is it worth the risk? PMID- 26853642 TI - Search continues for a CMV vaccine for transplant recipients. PMID- 26853643 TI - Safety and current status of blood transfusion in China: an update. PMID- 26853644 TI - Discontinuation therapy: the role of emotion and cognition. PMID- 26853646 TI - Anticoagulation with rivaroxaban for livedoid vasculopathy (RILIVA): a multicentre, single-arm, open-label, phase 2a, proof-of-concept trial. AB - BACKGROUND: Livedoid vasculopathy is a thrombotic skin disease characterised by recurrent occlusion of the cutaneous microcirculation in lower extremities, which results in skin infarctions with painful ulcerations and irreversible scar formation. Rivaroxaban is a direct factor Xa inhibitor that prevents thrombus formation. We investigated whether rivaroxaban is effective for the treatment of livedoid vasculopathy. METHODS: We did this single-arm, open-label, multicenter, phase 2a, proof-of concept trial at three university hospitals in Germany. Patients with livedoid vasculopathy and a minimum pain score of 40 on the visual analogue scale were eligible to participate. Patients received oral rivaroxaban tablets for 12 weeks at an initial dose of 10 mg twice per day, which was reduced to once per day if a reduction of pain by 50% on the visual analogue scale was achieved. Subcutaneous enoxaparin at 1 mg per kg bodyweight once or twice per day was allowed as a backup treatment in case of insufficient efficacy and increased pain. The primary endpoint was change in pain on the visual analogue scale from baseline to 12 weeks. Efficacy was assessed in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study drug. This trial is registered with the EU Clinical Trials Register, EudraCT number 2012-000108-13-DE, and is closed to new participants. FINDINGS: Between Dec 28, 2012, and April 24, 2014, 36 patients were screened, 28 patients were recruited for the study, and 25 patients received treatment. During treatment, five patients dropped out of the study because of withdrawal of consent (one patient), lack of compliance (one patient), violation of inclusion criteria (two patients), and a serious adverse event (one patient). Median pain on the visual analogue scale decreased from 65.0 (IQR 52.0-78.0) at baseline to 6.0 (1.0-14.0) after 12 weeks of treatment (p<0.0001). Six of the 20 patients required additional treatment with enoxaparin. Eight treatment-related adverse events were recorded in six (24%) of the 25 patients: five cases of menorrhagia including one classified as both menorrhagia and dysmenorrhoea, one case of dyspnoea, and one case of gingival bleeding. The only serious adverse reaction to rivaroxaban during the study was one case of menorrhagia in a patient with concomitant endometriosis, which resulted in study discontinuation. INTERPRETATION: Rivaroxaban seems to effectively reduce pain in livedoid vasculopathy. Therefore we suggest that rivaroxaban with enoxaparin as a backup treatment is a suitable treatment option for patients with livedoid vasculopathy. FUNDING: Deutsche Forschungsgemeinschaft and Bayer Vital. PMID- 26853647 TI - Early T-cell precursor acute lymphoblastic leukaemia in children treated in AIEOP centres with AIEOP-BFM protocols: a retrospective analysis. AB - BACKGROUND: Early T-cell precursor acute lymphoblastic leukaemia was recently recognised as a distinct leukaemia and reported as associated with poor outcomes. We aimed to assess the outcome of early T-cell precursor acute lymphoblastic leukaemia in patients from the Italian Association of Pediatric Hematology Oncology (AIEOP) centres treated with AIEOP-Berlin-Frankfurt-Munster (AIEOP-BFM) protocols. METHODS: In this retrospective analysis, we included all children aged from 1 to less than 18 years with early T-cell precursor acute lymphoblastic leukaemia immunophenotype diagnosed between Jan 1, 2008, and Oct 31, 2014, from AIEOP centres. Early T-cell precursors were defined as being CD1a and CD8 negative, CD5 weak positive or negative, and positive for at least one of the following antigens: CD34, CD117, HLADR, CD13, CD33, CD11b, or CD65. Treatment was based on AIEOP-BFM acute lymphoblastic leukaemia 2000 (NCT00613457) or AIEOP-BFM acute lymphoblastic leukaemia 2009 protocols (European Clinical Trials Database 2007-004270-43). The main differences in treatment and stratification of T-cell acute lymphoblastic leukaemia between the two protocols were that in the 2009 protocol only, pegylated L-asparaginase was substituted for Escherichia coli L asparaginase, patients with prednisone poor response received an additional dose of cyclophosphamide at day 10 of phase IA, and high minimal residual disease at day 15 assessed by flow cytometry was used as a high-risk criterion. Outcomes were assessed in terms of event-free survival, disease-free survival, and overall survival. FINDINGS: Early T-cell precursor acute lymphoblastic leukaemia was diagnosed in 49 patients. Compared with overall T-cell acute lymphoblastic leukaemia, it was associated with absence of molecular markers for PCR detection of minimal residual disease in 25 (56%) of 45 patients; prednisone poor response in 27 (55%) of 49 patients; high minimal residual disease at day 15 after starting therapy in 25 (64%) of 39 patients (bone marrow blasts >= 10%, by flow cytometry); no complete remission after phase IA in 7 (15%) of 46 patients (bone marrow blasts >= 5%, morphologically); and high PCR minimal residual disease (>= 5 * 10(-4)) at day 33 after starting therapy in 17 (85%) of 20 patients with markers available. Overall, 38 (78%) of 49 patients are in continuous complete remission, including 13 of 18 after haemopoietic stem cell transplantation, with three deaths in induction, five deaths after haemopoietic stem cell transplantation, and three relapses. Severe adverse events in the 2009 study were reported in 10 (30%) of 33 patients with early T-cell precursor acute lymphoblastic leukaemia versus 24 (15%) of 164 patients without early T-cell precursor acute lymphoblastic leukaemia and life-threatening events in induction phase IA occurred in 4 (12%) of 33 patients with early T-cell precursor acute lymphoblastic leukaemia versus 7 (4%) of 164 patients without early T-cell precursor acute lymphoblastic leukaemia. No difference was seen in the subsequent consolidation phase IB of protocol I. INTERPRETATION: Early T-cell precursor acute lymphoblastic leukaemia is characterised by poor early response to conventional induction treatment. Consolidation phase IB, based on cyclophosphamide, 6-mercaptopurine, and ara-C at conventional (non-high) doses is effective in reducing minimal residual disease. Although the number of patients and observational time are limited, patients with early T-cell precursor acute lymphoblastic leukaemia treated with current BFM stratification and treatment strategy have a favourable outcome compared with earlier reports. The role of innovative therapies and haemopoietic stem cell therapy in early T-cell precursor acute lymphoblastic leukaemia needs to be assessed. FUNDING: None. PMID- 26853649 TI - When will the government deliver? PMID- 26853645 TI - Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. AB - BACKGROUND: Post-thrombotic syndrome is a common complication after acute proximal deep vein thrombosis (DVT) and is associated with reduced quality of life and a substantial cost burden. In the 2-year results of the CaVenT study, additional catheter-directed thrombolysis reduced the risk of post-thrombotic syndrome by 14% compared with conventional therapy, but did not affect quality of life. In this study we report results at the 5-year follow-up, aiming to assess whether findings for post-thrombotic syndrome and quality of life have persisted. METHODS: Between Jan 3, 2006, and Dec 22, 2009, we recruited patients aged 18-75 years with a first-time high proximal leg DVT from 20 hospitals in the Norwegian southeastern health region. With sealed envelopes, participants were randomly assigned (1:1) to standard treatment with compression stockings and anticoagulants (control group) or to standard treatment plus catheter-directed thrombolysis with alteplase within 21 days from symptom onset. Pre-specified outcomes in this analysis were post-thrombotic syndrome at 5 years as assessed with the Villalta score and scores for quality of life at 5 years with EQ-5D and the disease-specific VEINES-QOL/Sym. Analyses were by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00251771. FINDINGS: At 5 year follow-up (last date Oct 14, 2014), data were available for 176 patients (84% of the 209 patients originally randomised)--87 originally assigned to catheter-directed thrombolysis and 89 originally assigned to the control group. 37 patients (43%; 95% CI 33-53) allocated to catheter-directed thrombolysis developed post-thrombotic syndrome, compared with 63 (71%; 95% CI 61-79) allocated to the control group (p<0.0001), corresponding to an absolute risk reduction of 28% (95% CI 14-42) and a number needed to treat of 4 (95% CI 2-7). Four (5%) patients assigned to catheter-directed thrombolysis and one (1%) to standard treatment had severe post-thrombotic syndrome (Villalta score >= 15 or presence of an ulcer). Quality-of-life scores with either assessment scale did not differ between the treatment groups. INTERPRETATION: Additional catheter directed thrombolysis resulted in a persistent and increased clinical benefit during follow-up for up to 5 years, supporting the use of additional catheter directed thrombolysis in patients with extensive proximal DVT. However, allocation to this therapy did not lead to better quality of life. The optimal endovascular thrombolytic approach needs further investigation. FUNDING: Southeastern Norway Regional Health Authority, the Research Council of Norway, University of Oslo, Oslo University Hospital. PMID- 26853650 TI - New strategy aims to ensure early detection of sepsis. PMID- 26853651 TI - UK volunteers to tackle Ebola deployed 'far too late'. PMID- 26853652 TI - Nurse of the year urges teamwork to stop domestic abuse. PMID- 26853653 TI - Official advice focuses on reducing waiting times. PMID- 26853648 TI - Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial. AB - BACKGROUND: Patients seropositive for cytomegalovirus (CMV) and undergoing allogeneic haemopoietic stem-cell transplantation (HCT) are at risk for CMV reactivation. Stimulating viral immunity by vaccination might achieve CMV viraemia control without the need for antiviral agents. CMVPepVax is a chimeric peptide composed of a cytotoxic CD8 T-cell epitope from CMV pp65 and a tetanus T helper epitope. It is formulated with the adjuvant PF03512676, a Toll-like receptor 9 agonist, which augments cellular immunity. We aimed to assess safety, immunogenicity, and possible clinical benefit of the CMVPepVax vaccine in patients undergoing HCT. METHODS: We did a randomised, open-label, phase 1b trial at one transplant centre in the USA. Eligible patients were CMV-seropositive, positive for HLA-A*0201, aged 18-75 years, and undergoing HCT from a matched related or matched-unrelated donor. Patients were reassessed for eligibility on day 28 after HCT. We randomly allocated patients to either the CMVPepVax vaccine or observation, in blocks stratified by CMV donor serostatus. CMVPepVax was administered subcutaneously on days 28 and 56. The primary outcome was safety, which consisted of secondary graft failure, grade III-IV acute GVHD, non-relapse mortality by day 100, serious adverse events related to the vaccine (judged by the data and safety monitoring committee [DSMC]) grade 3-4 adverse events related to the vaccine (judged by the DSMC) within 2 weeks of vaccination, and development of double-strand (ds) DNA autoantibodies. Statistical analyses included all randomised patients and were done per-protocol. This study is registered with ClinicalTrials.gov, number NCT01588015. This trial is closed to accrual and the final analysis is presented in this report. FINDINGS: Between Oct 31, 2012, and Nov 5, 2014, 36 eligible patients were allocated to either CMVPepVax (n=18) or observation (n=18), with no adverse effect on HCT (no secondary graft failures in either group) or cases of acute GVHD (seven patients assigned vaccine and six under observation had acute GVHD of grade 2 or less), and no unexpected adverse events. Compared with observation, better relapse-free survival was recorded in patients allocated the vaccine (seven vs one; hazard ratio [HR] 0.12, 95% CI 0.01-0.94; p=0.015). No patients had non-relapse mortality by day 100. One serious adverse event (grade 1 fever) was attributed to CMVPepVax but resolved within 48 h. Four patients assigned the vaccine had a serious adverse event, which was unrelated to the vaccine (grade 3 thrombocytopenia, grade 3 device-related infection, grade 2 nausea, and grade 1 fever), compared with nine patients under observation (grade 4 maculopapular rash, grade 3 nausea, grade 3 infection, grade 3 thrombotic thrombocytopenic purpurea, grade 2 nausea, grade 2 generalised muscle weakness, grade 2 infection, grade 1 fever, and grade 1 fatigue; p=0.16). 54 grade 3-4 adverse events were reported in patients assigned the vaccine compared with 91 in patients who were under observation (p=0.2). No patients had grade III-IV acute GVHD or developed dsDNA autoantibodies. INTERPRETATION: The results show safety and immunogenicity of the CMVPepVax vaccine. The prospect of substantial clinical benefits warrant testing in a phase 2 trial. FUNDING: National Cancer Institute. PMID- 26853654 TI - Mobile device identifies head injuries. PMID- 26853656 TI - Nurses raise concerns about shelved safe staffing guidance. PMID- 26853657 TI - Process for older people attending urgent care services streamlined. PMID- 26853658 TI - Janet Youd--The bigger picture. PMID- 26853663 TI - Board's eye view--Mental health reforms. PMID- 26853665 TI - Don't be shocked by the new. PMID- 26853671 TI - Are you ready for revalidation? AB - The new system of Nursing and Midwifery Council revalidation comes into effect in April 2016, from which time all nurses and midwives will be required to demonstrate their ability to practise safely and effectively. This article describes how one emergency department has incorporated evidence collection for revalidation into its regular continuing professional development opportunities, and outlines the benefits of this for individual nurses, employers and patients. PMID- 26853672 TI - Skills development at a paramedic accident simulation centre. AB - Practice simulation in acute and pre-hospital care settings is a growing area of interest for clinicians and health educationalists, and there is much evidence to support its use (Pike and O'Donnell 2010). Most simulation is delivered through computer-aided software or in virtual environments, however last year the University of Hertfordshire opened an accident simulation centre which is an outdoor facility that offers pre- and post-registration paramedics the opportunity to experience a range of scenarios in a 'real life' but secure environment. This article describes how the centre enables students to apply theory to practice in complex situations, such as managing patients injured in road traffic collisions. PMID- 26853673 TI - Identifying signs of intimate partner violence. AB - Intimate partner violence is a major public health and social problem that affects people everywhere. Nurses can play an important role in identifying victims who present to healthcare settings with domestic abuse-related health issues. Evidence suggests that most women who present to emergency departments have experienced domestic abuse at some point in their lives, but that only 5% are identified by healthcare professionals. To identify and respond to victims effectively, emergency nurses must understand domestic abuse and its associated complexities. This article provides an overview of these issues, including the different types of abuse, and their prevalence, causes and effects on health. The article also explores how emergency nurses can identify and manage the effects of violence at work. PMID- 26853674 TI - Blood products and their use in traumatic major haemorrhage. AB - Blood loss due to trauma is a leading cause of death in young people and is the result of the 'lethal triad' of hypothermia, acidosis and coagulopathy, which collectively reduce haemostasis. Emergency department nurses can help to reverse the triad through the timely and efficient use of blood products and fluids. This article briefly examines different blood groups, describes the elements of the lethal triad, and discusses the blood products used to transfuse patients with major haemorrhage. PMID- 26853675 TI - A Pd-Cu2O nanocomposite as an effective synergistic catalyst for selective semi hydrogenation of the terminal alkynes only. AB - A new type lead-free catalyst of a Pd-Cu2O nanocomposite was developed for highly selective semi-hydrogenation of alkynes. With unprecedented selectivity for the semi-hydrogenation of terminal alkynes to alkenes, we show for the first time that the catalyst only hydrogenated the terminal alkynes, i.e. did not hydrogenate the internal alkynes. PMID- 26853676 TI - Urinary incontinence in women in relation to occupational status. AB - Through this cross-sectional study the authors explore urinary incontinence in women in relation to occupational status and environment. Data from the fourth Korea National Health and Nutrition Examination Survey (2008-2009) were used (n = 5,928) excluding those aged under 19 or over 65 years, male, with renal disease, and with missing data. Urinary incontinence was prevalent in working women. Compared to unemployed women, the adjusted odds ratio (95% confidence intervals) for women working in services/sales was 1.62 (1.21-2.19); for paid workers was 1.81 (1.20-2.73); and for self-employed workers was 1.46 (1.05-2.03). Compared to unemployed women, the adjusted odds ratio for working women with a daytime work schedule was 2.14 (1.18-3.87), while for those with evening work schedules, it was 1.35 (1.05-1.74). Urinary incontinence was significantly associated with various occupational environments: an unclean and uncomfortable workplace, dangerous job and probability of accidents, feeling pressed for time, awkward position for long periods, and carrying heavy weights. These findings suggest that urinary incontinence was prevalent in working women and was associated with occupational status and working environment. Therefore, improving occupational status and environment for working women-such as modifying the working schedule, posture, and workplace atmosphere-are needed to prevent urinary incontinence. PMID- 26853677 TI - Straightforward synthesis of functionalized chroman-4-ones through cascade radical cyclization-coupling of 2-(allyloxy)arylaldehydes. AB - A novel and direct approach to synthesize a series of phosphonate, azide and hydroxy functionalized chroman-4-ones has been developed. The cascade transformation appears to proceed through an intramolecular addition of an in situ generated acyl radical onto the alkene, followed by a selective nucleophilic radical-electrophilic radical cross coupling. PMID- 26853678 TI - Emerging roles of pro-resolving lipid mediators in immunological and adaptive responses to exercise-induced muscle injury. AB - Lipid mediators are bioactive metabolites of the essential polyunsaturated fatty acids (PUFA) that play diverse roles inthe initiation, self-limitation, and active resolution of inflammation. Prostaglandins, classical pro-inflammatory lipid metabolites of arachidonic acid, have long been implicated in immunological and adaptive muscle responses to acute injury and exercise-induced stress. More recently, PUFA metabolites have been discovered during the resolution phase of inflammation which collectively function as endogenous 'stop signals' to control inflammation whilst actively promoting the return to a non-inflamed state. The apparent self-resolving nature of inflammatory responses holds important implications for contexts of musculoskeletal injury, exercise recovery, and chronic inflammatory diseases originati ng in or impacting upon muscle. 'Anti inflammatory' interventions that strive to control inflammation via antagonism of pro-inflammatory signals are currently commonplace in efforts to hasten muscle recovery from damaging or exhaustive exercise, as well as to relieve the pain associated with musculoskeletal injury. However, the scientific literature does not clearly support a benefit of this anti-inflammatory approach. Additionally, recent evidence suggests that strategies to block pro-inflammatory lipid mediator pathways (e.g. NSAIDs) may be counterintuitive and inadvertently derange or impair timely resolution of inflammation; with potentially deleterious implications on skeletal muscle remodelling. The current review will provide an overview of the current understanding of diverse roles of bioactive lipid mediators in the initiation, control, and active resolution of acute inflammation. The established and putative roles of lipid mediators in mediating immunological and adapt ive skeletal muscle responses to acute muscle injury and exercise-induced muscle load/stress will be discussed. PMID- 26853679 TI - A theoretical study on charge transport of dithiolene nickel complexes. AB - Organic semiconducting materials play an important role in the fabrication of high performance organic electronic devices. In the present work, we theoretically designed a series of organic semiconductors based on nickel complexes. Their characteristics of charge transport were investigated using DFT computational approaches. Based on the computed results, all compounds designed are found to be excellent candidates for ambipolar organic semiconductors with low reorganization energies for both holes and electrons. The (I-V) characteristics and transmission spectra of materials show that the replacement of benzene rings by thiophene rings results in an increase of their HOMO and LUMO energy levels. HOMOs of compounds containing thiophene end-groups are likely dominant for their conductance, while LUMOs of compounds containing benzene end groups mainly affect their conductance. The electron distribution in these frontier MOs is identified as the main reason which makes the conductance of the compounds in the first series higher than those in the later series. PMID- 26853680 TI - A systematic review on randomized control trials on rennin angiotensin aldosterone system inhibitors role in managing hypertension among hemodialysis patients. AB - Randomized control trials (RCTs) are considered as most rigors way of determining the cause-effect relationship of a treatment and outcome. Activation of rennin angiotensin aldosterone system (RAAS) is an important contributor to hypertension in hemodialysis patients. The prevalence of hypertension in hemodialysis patients varies from 60% to 80% and hypertension management alone with conventional hemodialysis is insufficient. Hence, the current review was aimed to investigate the effect of RAAS inhibitors in managing hypertension among hemodialysis patients in a randomized control trial. Using PUBMED and EMBASE databases, randomized control trial with primary or secondary outcomes related to the effect of RAAS inhibitors on blood pressure among hemodialysis patients were included for analysis. The current review also assessed the quality of reporting of RCT. A total of eight RCT met inclusion criteria for current review. According to modified jaded scale, one (12.5%) study scored four points for quality reporting, whereas two (25%) studies scored one point that was the least score. The mean score for all included studies was 2.25. Six (75%) of the eight RCT included, involved ARB in hypertension management among hemodialysis patients, whereas two (25%) studies involved angiotensin-converting enzyme (ACE) inhibitors. Of the siz RCT involving ARB, two (33.3%) RCT also included ACE inhibitors comparison group. Altogether six (75%) studies report a reduction in blood pressure with the use of RAAS inhibitors compared to control group; however, of the six studies, two (33.3%) reported that the reduction in blood pressure was not significant. Whereas, two (25%) studies reported no reduction in blood pressure compared to the control group. The findings from current review do not indicate a clear pattern for a role of RAAS inhibitors for hypertension control among hemodialysis patients. PMID- 26853682 TI - Shape-dependent internalization kinetics of nanoparticles by membranes. AB - Internalization of nanoparticles by biomembranes is critical for nanomedicine development; however, this process, especially its dynamics aspect, is still not well understood. Using coarse-grained molecular modeling combined with free energy calculations, we studied the endocytic process for spherical, prolate and oblate particles with varied aspect ratios, volumes and interaction strengths. Rich dynamic wrapping behaviors have been observed. Small ellipsoids follow a pathway that includes particle laying-down, membrane invagination and wrapping, and then disruption of the membrane neck. However, the step of particle laying down is skipped for large ellipsoids. Because of the significantly decreased local mean curvature at the side edge (oblate ellipsoid) or tips (prolate ellipsoid), the rotation is less favorable for particles with larger volume. Given the existence of a local minimum and an energy barrier during the endocytic process presented by our free energy calculations, the oblate particle provides longer endocytic time than the corresponding prolate particle. For large particles, the free energy surfaces are smooth, with no local minimum. When we increase the interaction strength between the membrane and the particle, the endocytic process is greatly affected. Moreover, a "sandwiched structure", in which the particle lays between the two membrane layers, was observed for both prolate and oblate particles. PMID- 26853683 TI - Recent developments in novel freezing and thawing technologies applied to foods. AB - This article reviews the recent developments in novel freezing and thawing technologies applied to foods. These novel technologies improve the quality of frozen and thawed foods and are energy efficient. The novel technologies applied to freezing include pulsed electric field pre-treatment, ultra-low temperature, ultra-rapid freezing, ultra-high pressure and ultrasound. The novel technologies applied to thawing include ultra-high pressure, ultrasound, high voltage electrostatic field (HVEF), and radio frequency. Ultra-low temperature and ultra rapid freezing promote the formation and uniform distribution of small ice crystals throughout frozen foods. Ultra-high pressure and ultrasound assisted freezing are non-thermal methods and shorten the freezing time and improve product quality. Ultra-high pressure and HVEF thawing generate high heat transfer rates and accelerate the thawing process. Ultrasound and radio frequency thawing can facilitate thawing process by volumetrically generating heat within frozen foods. It is anticipated that these novel technologies will be increasingly used in food industries in the future. PMID- 26853684 TI - CoS(2x)Se(2(1-x)) nanowire array: an efficient ternary electrocatalyst for the hydrogen evolution reaction. AB - Binary transition metal dichalcogenides (TMDs) have emerged as efficient catalysts for the hydrogen evolution reaction (HER). Co-based TMDs, such as CoS2 and CoSe2, demonstrate promising HER performance due to their intrinsic metallic nature. Recently, the ternary electrocatalysts were widely acknowledged for their prominent efficiency as compared to their binary counterparts due to increased active sites caused by the incorporation of different atoms. Herein, we successfully grew the ternary CoS2xSe2(1-x) (x = 0.67) nanowires (NWs) on a flexible carbon fiber. As a superior electrocatalyst, ternary CoS2xSe2(1-x) NWs arrays demonstrated excellent catalytic activity for electrochemical hydrogen evolution in acidic media, achieving current densities of 10 mA cm(-2) and 100 mA cm(-2) at overpotentials of 129.5 mV and 174 mV, respectively. Notably, the high stability of CoS2xSe2(1-x) NWs suggested that the ternary CoS2xSe2(1-x) NWs are a scalable catalyst for electrochemical hydrogen evolution. PMID- 26853685 TI - The applied research of MRI with ASSET-EPI-FLAIR combined with 3D TOF MRA sequences in the assessment of patients with acute cerebral infarction. AB - Background To extend the time window for thrombolysis, reducing the time for diagnosis and detection of acute cerebral infarction seems to be warranted. Purpose To evaluate the feasibility of implementing an array spatial sensitivity technique (ASSET)-echo-planar imaging (EPI)-fluid attenuated inversion recovery (FLAIR) (AE-FLAIR) sequence into an acute cerebral infarction magnetic resonance (MR) evaluation protocol, and to assess the diagnostic value of AE-FLAIR combined with three-dimensional time-of-flight MR angiography (3D TOF MRA). Material and Methods A total of 100 patients (68 men, 32 women; age range, 44-82 years) with acute cerebral infarction, including 50 consecutive uncooperative and 50 cooperative patients, were evaluated with T1-weighted (T1W) imaging, T2-weighted (T2W) imaging, FLAIR, diffusion-weighted imaging (DWI), 3D TOF, EPI-FLAIR, and AE FLAIR. Conventional FLAIR, EPI-FLAIR, and AE-FLAIR were assessed by two observers independently for image quality. The optimized group (AE-FLAIR and 3D TOF) and the control group (T1W imaging, T2W imaging, conventional FLAIR, DWI, and 3D TOF) were compared for evaluation time and diagnostic accuracy. Results One hundred and twenty-five lesions were detected and images having adequate diagnostic image quality were in 73% of conventional FLAIR, 62% of EPI-FLAIR, and 89% of AE-FLAIR. The detection time was 12 +/- 1 min with 76% accuracy and 4 +/- 0.5 min with 100% accuracy in the control and the optimized groups, respectively. Inter-observer agreements of kappa = 0.78 and kappa = 0.81 were for the optimized group and control group, respectively. Conclusion With reduced acquisition time and better image quality, AE-FLAIR combined with 3D TOF may be used as a rapid diagnosis tool in patients with acute cerebral infarction, especially in uncooperative patients. PMID- 26853686 TI - Increased aortic wall thickness on CT as a sign of prosthetic valve endocarditis. AB - Background Increased wall thickness in the aortic root has been suggested as an early sign of prosthetic valve endocarditis (PVE). However, there are no previous studies on the aortic wall thickness after aortic valve replacement (AVR) or in patients with PVE. Purpose To identify a clinically useful cutoff value for aortic wall thickness to detect PVE. Material and Methods Chest computed tomography (CT) studies (n = 303) on patients with a prosthetic aortic valve were retrospectively analyzed. CT studies on patients without PVE (n = 260) were compared with CT studies on patients with definite PVE (n = 43). A receiver operator characteristic (ROC) analysis was performed. Results In non-PVE patients, the wall thickness during the first 3 months postoperatively (n = 70, 4.5 +/- 1.7 mm) was increased compared to beyond 3 months postoperatively (n = 190, 3.2 +/- 1.0 mm, P < 0.001). Beyond 3 months postoperatively, the wall thickness 95th percentile was 5.0 mm without signs of further decrease with time. The wall thickness in PVE patients was 6.8 +/- 3.0 mm (n = 43). Beyond 3 months postoperatively, ROC analysis yielded an area under the curve of 0.89 (95% CI, 0.81-0.96). With a cutoff value of 5 mm the sensitivity was 67%, specificity 95%, positive likelihood ratio 14.1, and negative likelihood ratio 0.35 of increased wall thickness in detecting PVE. Conclusion In the early postoperative period after AVR, the aortic wall thickness is increased compared to the late postoperative period. After 3 months, the wall thickness has decreased and stabilized. Increased wall thickness (>5 mm) beyond 3 months postoperatively significantly increases the likelihood of PVE. PMID- 26853687 TI - Survey of cognitive rehabilitation practices in the state of Kuwait. AB - : Background Rehabilitation professionals must be astute at recognizing, assessing, and treating individuals with cognitive deficits. No research is available to examine cognitive rehabilitation practices applied to individuals with neurological conditions in Kuwait. OBJECTIVES: To identify the use of cognitive assessments, the availability of resources, and the barriers to cognitive rehabilitation practices in Kuwait. Methods Face-to-face interviews were conducted with health care professionals working with adult individuals with neurological conditions. These professionals included occupational therapists, speech-language pathologists, psychiatrists, and neurologists. Results The most commonly used cognitive based assessments are MMSE (41%), and MoCA and LOTCA (15.2%). The only clinical assessment used is the Line-Bisection Test (2.2%). The most used occupation-based assessments are FIM (6.5%), COPM (4.3%), the Interest Checklist (2.2%), and the Barthel Index (2.2%). Resources related to cognitive rehabilitation in Kuwait that are unavailable to practitioners include journal clubs (91%), special interest groups (89%), and continuing education programmes (82.6%). Barriers to cognitive rehabilitation practice included lack of sufficient funds for continuing education, lack of time, lack of standardized assessments, and lack of inter-professional teamwork. Conclusion Many adults in Kuwait live with cognitive impairment. There is a need to develop appropriate evidence-based cognitive rehabilitation clinical guidelines in Kuwait. PMID- 26853688 TI - Selection of accurate reference genes in mouse trophoblast stem cells for reverse transcription-quantitative polymerase chain reaction. AB - Mouse trophoblast stem cells (TSCs) form colonies of different sizes and morphologies, which might reflect their degrees of differentiation. Therefore, each colony type can have a characteristic gene expression profile; however, the expression levels of internal reference genes may also change, causing fluctuations in their estimated gene expression levels. In this study, we validated seven housekeeping genes by using a geometric averaging method and identified Gapdh as the most stable gene across different colony types. Indeed, when Gapdh was used as the reference, expression levels of Elf5, a TSC marker gene, stringently classified TSC colonies into two groups: a high expression groups consisting of type 1 and 2 colonies, and a lower expression group consisting of type 3 and 4 colonies. This clustering was consistent with our putative classification of undifferentiated/differentiated colonies based on their time-dependent colony transitions. By contrast, use of an unstable reference gene (Rn18s) allowed no such clear classification. Cdx2, another TSC marker, did not show any significant colony type-specific expression pattern irrespective of the reference gene. Selection of stable reference genes for quantitative gene expression analysis might be critical, especially when cell lines consisting of heterogeneous cell populations are used. PMID- 26853690 TI - Membrane Translocation and Assembly of Sugar Polymer Precursors. AB - Bacterial polysaccharides play an essential role in cell viability, virulence, and evasion of host defenses. Although the polysaccharides themselves are highly diverse, the pathways by which bacteria synthesize these essential polymers are conserved in both Gram-negative and Gram-positive organisms. By utilizing a lipid linker, a series of glycosyltransferases and integral membrane proteins act in concert to synthesize capsular polysaccharide, teichoic acid, and teichuronic acid. The pathways used to produce these molecules are the Wzx/Wzy-dependent, the ABC-transporter-dependent, and the synthase-dependent pathways. This chapter will cover the initiation, synthesis of the various polysaccharides on the cytoplasmic face of the membrane using nucleotide sugar precursors, and export of the nascent chain from the cytoplasm to the extracellular milieu. As microbial glycobiology is an emerging field in Gram-positive bacteria research, parallels will be drawn to the more widely studied polysaccharide biosynthesis systems in Gram-negative species in order to provide greater understanding of these biologically significant molecules. PMID- 26853691 TI - Exopolysaccharide Production and Biofilm Formation by Histophilus somni. AB - The biofilm matrix of Histophilus somni is a complex architecture that differs substantially in structure between a pathogenic and commensal isolate examined. Overall, most pathogenic isolates produce more biofilm than commensal isolates. A major component of the biofilm is exopolysaccharide (EPS), which is also produced in greater quantity in the pathogenic isolate than in the commensal isolate studied. The EPS is composed of a D-mannan polymer, with occasional galactose residues present on side chains, similar in composition to that of yeast mannan. When grown in the presence of sialic acid, the biofilm EPS becomes sialylated and the amino sugars N-acetylglucosamine and N-acetylgalactosamine can be detected. In vitro biofilm formation follows a typical 4-stage growth curve, characterized by attachment, growth, maturation, and detachment. Following experimental challenge, formation of an H. somni biofilm has been demonstrated in cardiopulmonary tissue, often with Pasteurella multocida cohabitating the biofilm. A recently developed diagnostic test can detect antibodies to the EPS only in animals with systemic disease due to H. somni and is therefore capable of distinguishing between healthy animals colonized with H. somni and animals with systemic disease. PMID- 26853689 TI - The cystathionine-beta-synthase domains on the guanosine 5''-monophosphate reductase and inosine 5'-monophosphate dehydrogenase enzymes from Leishmania regulate enzymatic activity in response to guanylate and adenylate nucleotide levels. AB - The Leishmania guanosine 5'-monophosphate reductase (GMPR) and inosine 5' monophosphate dehydrogenase (IMPDH) are purine metabolic enzymes that function maintaining the cellular adenylate and guanylate nucleotide. Interestingly, both enzymes contain a cystathionine-beta-synthase domain (CBS). To investigate this metabolic regulation, the Leishmania GMPR was cloned and shown to be sufficient to complement the guaC (GMPR), but not the guaB (IMPDH), mutation in Escherichia coli. Kinetic studies confirmed that the Leishmania GMPR catalyzed a strict NADPH dependent reductive deamination of GMP to produce IMP. Addition of GTP or high levels of GMP induced a marked increase in activity without altering the Km values for the substrates. In contrast, the binding of ATP decreased the GMPR activity and increased the GMP Km value 10-fold. These kinetic changes were correlated with changes in the GMPR quaternary structure, induced by the binding of GMP, GTP, or ATP to the GMPR CBS domain. The capacity of these CBS domains to mediate the catalytic activity of the IMPDH and GMPR provides a regulatory mechanism for balancing the intracellular adenylate and guanylate pools. PMID- 26853692 TI - Maternal BMI, gestational diabetes, and weight gain in relation to childhood obesity: The mediation effect of placental weight. AB - OBJECTIVE: High prepregnancy body mass index (BMI), excessive gestational weight gain (GWG), and gestational diabetes mellitus (GDM) are associated with the risk of childhood obesity. This study aims to examine the extent to which these effects may be mediated through the placenta. METHODS: Data included 33,893 mothers and their singleton infants from birth to 7 years old (total 154,590 visits) in the Collaborative Perinatal Project, a U.S. multicenter prospective cohort study from 1959 to 1976. The placentas were weighed after removing cord and membranes. We performed sequential generalized estimating equation-linear models excluding and including placental weight to evaluate its mediation effect. RESULTS: In this population, 21.7% of mothers had overweight or obesity, 17.3% had excessive GWG, and 350 (1%) had diagnosed GDM; in addition, 7.2% children had obesity. After adjustment for prepregnancy BMI and other covariates, childhood BMI was 0.23 (95% CI: 0.05, 0.40) kg/m(2) higher for children born to mothers with GDM versus those without GDM. Inclusion of placental weight in the model attenuated the association by 52% to 0.11 (95% CI: -0.06, 0.28) and similarly attenuated the associations with childhood BMI for GWG by 25% and maternal prepregnancy BMI by 17%. CONCLUSIONS: Placental weight partly mediates the effects of prepregnancy BMI, excessive GWG, and GDM on childhood BMI. PMID- 26853693 TI - Value thy postdoc, or s/he might be lost to gas fitting.... PMID- 26853694 TI - MicroRNA signatures characterizing caste-independent ovarian activity in queen and worker honeybees (Apis mellifera L.). AB - Queen and worker honeybees differ profoundly in reproductive capacity. The queen of this complex society, with 200 highly active ovarioles in each ovary, is the fertile caste, whereas the workers have approximately 20 ovarioles as a result of receiving a different diet during larval development. In a regular queenright colony, the workers have inactive ovaries and do not reproduce. However, if the queen is sensed to be absent, some of the workers activate their ovaries, producing viable haploid eggs that develop into males. Here, a deep-sequenced ovary transcriptome library of reproductive workers was used as supporting data to assess the dynamic expression of the regulatory molecules and microRNAs (miRNAs) of reproductive and nonreproductive honeybee females. In this library, most of the differentially expressed miRNAs are related to ovary physiology or oogenesis. When we quantified the dynamic expression of 19 miRNAs in the active and inactive worker ovaries and compared their expression in the ovaries of virgin and mated queens, we noted that some miRNAs (miR-1, miR-31a, miR-13b, miR 125, let-7 RNA, miR-100, miR-276, miR-12, miR-263a, miR-306, miR-317, miR-92a and miR-9a) could be used to identify reproductive and nonreproductive statuses independent of caste. Furthermore, integrative gene networks suggested that some candidate miRNAs function in the process of ovary activation in worker bees. PMID- 26853695 TI - Association of coronary artery calcification with liver fibrosis in Japanese patients with non-alcoholic fatty liver disease. AB - AIMS: Cardiovascular events are the leading cause of death among patients with non-alcoholic fatty liver disease (NAFLD), but their relationship remains unclear. This study examined the association between coronary atherosclerosis and liver fibrosis, represented by the coronary artery calcification (CAC) score and non-invasive fibrosis markers, respectively. METHODS: Among 698 patients with chest pain or electrocardiographic abnormalities who underwent coronary computed tomography (CT) between April 2006 and March 2010, those with known liver disorders or history of emergency coronary angioplasty were excluded, leaving 366 patients for this study. Diagnosis of NAFLD was based on abdominal CT and history of alcohol consumption. Subjects with CAC of 100 AU or more were categorized into the high-risk group for cardiovascular events. Patient records were examined for clinical parameters including CAC score and non-invasive fibrosis marker FIB-4 index. RESULTS: Ninety-four patients (25.7%) had NAFLD. In this group, univariate analysis identified old age, high diastolic blood pressure, high liver to spleen ratio and high FIB-4 index as risk factors for cardiovascular events and multivariate analysis identified age of 66 years or older and FIB-4 index of 2.09 or more as the significant risk factors. For the observation period until August 2014, the cumulative proportion of PCI performance was significantly higher in patients with FIB-4 of 2.09 or more than those with FIB-4 of less than 2.09. CONCLUSION: The progression of arteriosclerosis and that of liver fibrosis may be associated in NAFLD patients. The FIB-4 index can be easily determined and thus can be a useful marker for predicting cardiovascular events in NAFLD patients. PMID- 26853696 TI - Early Onset Drinking Predicts Greater Level But Not Growth of Alcohol-Induced Blackouts Beyond the Effect of Binge Drinking During Emerging Adulthood. AB - BACKGROUND: Early onset drinking is associated with later heavy drinking and related consequences. Early drinking onset and binge drinking are also independently associated with blackouts, which are periods of amnesia for events during a drinking episode. The objective of this study was to examine how early onset drinking relates to changes in the frequency of experiencing blackouts across 3 years controlling for year-specific binge drinking. METHODS: Participants (N = 1,145; 67.9% female) from a 6-year, longitudinal study are included in these analyses. Measures of self-reported age at drinking onset included ages at first drink, first high, and first drunk, which were used to create a latent early onset drinking factor. Frequency of binge drinking and blackouts were assessed annually during Years 4 to 6. RESULTS: Overall, 69.2% of participants reported experiencing blackouts. After controlling for year-specific binge drinking, a growth curve model indicated that early onset drinkers reported more frequent blackouts at Year 4. There were, however, no significant effects of acceleration or deceleration in the frequency of blackouts across the 3 years. Early onset drinkers continued to experience more frequent blackouts compared with those who initiated alcohol use later, despite decreases in binge drinking over time. CONCLUSIONS: Early onset drinkers reported more frequent blackouts across all 3 years, indicating that early alcohol initiation predisposes those individuals to continue to experience more frequent blackouts, despite a decrease in their binge drinking. This may be due to various factors, such as altered hippocampal development and functioning resulting from early alcohol exposure. PMID- 26853697 TI - A cumulative genetic risk score predicts progression in Parkinson's disease. AB - BACKGROUND: The contribution of genetic variability to clinical heterogeneity in Parkinson's disease is insufficiently understood. We aimed to investigate the effect of cumulative genetic risk on clinical outcomes. METHODS: In a single center study of 336 patients we genotyped 19 independent susceptibility variants identified in genome-wide association studies of Parkinson's disease. We tested for association between a cumulative genetic risk score and 3 outcome measures: survival, time until progression to Hoehn and Yahr stage 3, and Unified Parkinson's Disease Rating Scale motor score severity. RESULTS: Genetic risk score was significantly associated with time from diagnosis to Hoehn and Yahr stage 3 in a Cox regression model (P = 0.010). We observed no clear association for the other outcomes. CONCLUSIONS: We present results linking cumulative genetic risk to a motor outcome in Parkinson's disease. Our findings provide a valuable starting point for future large-scale efforts to map the genetic determinants of phenotypic variability. PMID- 26853698 TI - Circulating microRNA expression profiles in pre-eclampsia: evidence of increased miR-885-5p levels. AB - OBJECTIVE: To validate and to compare the circulating microRNA (miR) expression profiles between pre-eclampsia and healthy pregnant women, to perform correlation analysis of the differently expressed miRs with clinical and biochemical parameters, and to verify the extracellular localisation of miRs in apoptotic bodies, microvesicles, and exosomes. DESIGN: A case-control study with a replication study. SETTING: Pregnant women attending maternity hospitals in Southeastern Brazil. POPULATION: Two obstetric white populations: a case-control study (19 pre-eclampsia and 14 healthy pregnant) and a replication study (eight pre-eclampsia and eight healthy pregnant). METHODS: PCR-array with 84 different miRs was performed in plasma from five pre-eclampsia and four healthy pregnant women. In the case-control study, differently expressed miRs were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and correlated with clinical and biochemical parameters. The plasma was then fractioned to study the extracellular localisation of miRs. MAIN OUTCOME MEASURES: Gene expression profiles of miRs. RESULTS: From PCR-array, three miRs (miR-376c-3p, miR-19a-3p, and miR-19b-3p) were found to be down-regulated and the miR-885-5p was found to be up-regulated in pre-eclampsia compared with healthy pregnant women. In the validation step, miR-885-5p was the only significantly different miR (fold-change = 5.0, P < 0.05), which was confirmed in the replication study (fold-change = 4.5, P < 0.05). Moreover, miR-885-5p was significantly correlated with the hepatic enzyme aspartate transaminase (r = 0.66; P = 0.0034) and it was mostly associated with the exosomes (32-fold higher than apoptotic bodies). CONCLUSIONS: miR-885-5p is increased in plasma from pre eclampsia compared with healthy pregnant women, and it is released into circulation mainly inside exosomes. TWEETABLE ABSTRACT: miR-885-5p is increased in pre-eclampsia and is released into circulation mainly inside exosomes. PMID- 26853699 TI - Comparative effects of two different doses of low-level laser therapy on wound healing third-degree burns in rats. AB - Burns are injuries caused by direct or indirect contact to chemical, physical, or biological agents. Low-level laser therapy (LLLT) is a promising treatment since it is low-cost, non-invasive, and induces cell proliferation. This study aimed to investigate the effects of LLLT (660 nm) at two different fluences (12.5 J/cm(2) and 25 J/cm(2) ) per point of application on third-degree burns in rats. Thirty rats (Wistar) divided into GC, GL12.5, and GL25 were used in the study, and submitted to burn injury through a soldering iron at 150 degrees C, pressed on their back for 10 s. LLLT was applied immediately, and 2, 4, 6, and 8 days after wound induction. Histological analysis revealed a decreased inflammatory infiltrate in the group treated with 25 J/cm(2) , and intense inflammatory infiltrate in the control group and in the group treated with 12.5 J/cm(2) . The immunostaining of COX-2 was more intense in the control groups and in the group treated with 12.5 J/cm(2) than in the group treated with 25 J/cm(2) . Conversely, VEGF immunomarking was more expressive in the group treated with 25 J/cm(2) than it was in the other two groups. Therefore, our findings suggest that the use of 25 J/cm(2) and 1 J of energy was more effective in stimulating the cellular processes involved in tissue repair on third-degree burns in rats by reducing the inflammatory phase, and stimulating angiogenesis, thus restoring the local microcirculation which is essential for cell migration. PMID- 26853700 TI - Towards Redox-Driven Unidirectional Molecular Motion. AB - Redox-driven molecular motion is an attractive alternative to light-driven processes. Here, the ability of an overcrowded alkene-based unimolecular light driven rotary motor (A) to be driven by oxidation/reduction cycles is explored. We show that two-electron oxidation of A is followed by irreversible deprotonation and reduction to form a monocationic species D(+) , in which the stereogenic center is lost. This latter species was isolated through preparative electrolysis and its structure was confirmed by using single-crystal X-ray analysis. However, at short timescales and in the absence of Bronsted acids, these processes can be outrun and the oxidation of A to a dicationic species B(2+) occurs, in which the central double bond (the axle of the molecular motor) becomes a single bond; when followed by rapid reduction, it results in the reformation of A, potentially in both its stable and unstable conformations. The latter conformation, if formed, undergoes thermal helix inversion, completing a rotary cycle. The data obtained regarding these reactions provide a window of opportunity for the motor to be driven electrochemically, without degradation from chemical reactions of the oxidized motor. PMID- 26853701 TI - Photoinduced p- to n-type Switching in Thermoelectric Polymer-Carbon Nanotube Composites. AB - UV-induced switching from p- to n-type character is demonstrated during deposition of carbon-nanotube-conjugated polymer composites. This opens the possibility to photopattern n-type regions within an otherwise p-type film, which has a potential for complementary circuitry or, as shown here, thermoelectric generators made from a single solution. PMID- 26853703 TI - Upward shift of the vortex solid phase in high-temperature-superconducting wires through high density nanoparticle addition. AB - We show a simple and effective way to improve the vortex irreversibility line up to very high magnetic fields (60T) by increasing the density of second phase BaZrO3 nanoparticles. (Y0.77,Gd0.23)Ba2Cu3Oy films were grown on metal substrates with different concentration of BaZrO3 nanoparticles by the metal organic deposition method. We find that upon increase of the BaZrO3 concentration, the nanoparticle size remains constant but the twin-boundary density increases. Up to the highest nanoparticle concentration (n ~ 1.3 * 10(22)/m(3)), the irreversibility field (Hirr) continues to increase with no sign of saturation up to 60 T, although the vortices vastly outnumber pinning centers. We find extremely high Hirr, namely Hirr = 30 T (H||45 degrees ) and 24 T (H||c) at 65 K and 58 T (H||45 degrees ) and 45 T (H||c) at 50K. The difference in pinning landscape shifts the vortex solid-liquid transition upwards, increasing the vortex region useful for power applications, while keeping the upper critical field, critical temperature and electronic mass anisotropy unchanged. PMID- 26853702 TI - Delayed oral toxicity from long-term vemurafenib therapy. PMID- 26853705 TI - Characterization and Physicochemical Properties of Condensed Tannins from Acacia catechu. AB - Condensed tannins from Acacia catechu were carefully studied to determine their chemical structure and physicochemical properties. The combined use of MALDI-TOF MS and (13)C NMR revealed that catechin and epicatechin are the predominant monomers. Most of the compounds were dimers, as confirmed by size exclusion chromatography measurements. To evaluate their potential as aromatic building block in polymer synthesis, special care was given to the characterization and quantification of the different OH groups. A detailed (31)P NMR analysis showed the predominance of catechin, with a catechin/epicatechin ratio of 4.2:1. Two distinct (1)H NMR measurements confirmed the quantification. The thermal properties were also determined: the tannins showed a high temperature of degradation (ca. 190 degrees C) and a high glass transition temperature (ca. 140 degrees C), allowing for thermal processing or chemical reactions at relatively high temperature. A. catechu tannins thus present interesting features to be used as aromatic building blocks in polymer materials. PMID- 26853704 TI - Towards the development of multifunctional molecular indicators combining soil biogeochemical and microbiological variables to predict the ecological integrity of silvicultural practices. AB - The impact of mechanical site preparation (MSP) on soil biogeochemical structure in young larch plantations was investigated. Soil samples were collected in replicated plots comprising simple trenching, double trenching, mounding and inverting site preparation. Unlogged natural mixed forest areas were used as a reference. Analysis of soil nutrients, abundance of bacteria and gas exchanges unveiled no significant difference among the plots. However, inverting site preparation resulted in higher variations of gas exchanges when compared with trenching, mounding and unlogged natural forest. A combination of the biological and physicochemical variables was used to define a multifunctional classification of the soil samples into four distinct groups categorized as a function of their deviation from baseline ecological conditions. According to this classification model, simple trenching was the approach that represented the lowest ecological risk potential at the microsite level. No relationship was observed between MSP method and soil bacterial community structure as assessed by high-throughput sequencing of bacterial 16S rRNA gene; however, indicator genotypes were identified for each multifunctional soil class. This is the first identification of multifunctional molecular indicators for baseline and disturbed ecological conditions in soil, demonstrating the potential of applied microbial ecology to guide silvicultural practices and ecological risk assessment. PMID- 26853706 TI - Cross-talk between freezing response and signaling for regulatory transcriptions of MIR475b and its targets by miR475b promoter in Populus suaveolens. AB - MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in post transcriptional regulation of their target genes, yet the transcriptional regulation of plant miRNAs by promoter is poorly understood. Here, we firstly clone pri-miR475b cDNA and its native promoter from P. suaveolens, and characterize Psu-MIR475b as class-II gene transcribed by RNA polymerase II. By 5' deletion analysis of Psu-miR475b promoter in a series of promoter-GUS chimeric vectors, we functionally identify three positive regulatory regions and multiple cis-acting elements responsible for Psu-miR475b promoter activity in response to freezing stress and exogenous hormone treatment. Moreover, the Psu-miR475b promoter activity displays a tissue-specific manner, negatively regulated by freezing stress and positively by MeJA, SA or GA treatment. Importantly, we comparatively analyze the time-course transcriptional profiles of Psu-miR475b and its targets in Psu-miR475b over-expression transgenic plants controlled by Psu miR475b-specific promoter or CaMV 35S constitutive promoter, and explore the regulatory mechanism of Psu-miR475b promoter controlling transcriptional expressions of Psu-MIR475b and its targets in response to freezing stress and exogenous hormone treatment. Our results reveal that Psu-miR475b promoter mediated transcriptions of Psu-MIR475b and its targets in response to freezing stress may be involved in a cross-talk between freezing response and stress signaling process. PMID- 26853707 TI - MicroRNAs activate gene transcription epigenetically as an enhancer trigger. AB - MicroRNAs (miRNAs) are small non-coding RNAs that function as negative gene expression regulators. Emerging evidence shows that, except for function in the cytoplasm, miRNAs are also present in the nucleus. However, the functional significance of nuclear miRNAs remains largely undetermined. By screening miRNA database, we have identified a subset of miRNA that functions as enhancer regulators. Here, we found a set of miRNAs show gene-activation function. We focused on miR-24-1 and found that this miRNA unconventionally activates gene transcription by targeting enhancers. Consistently, the activation was completely abolished when the enhancer sequence was deleted by TALEN. Furthermore, we found that miR-24-1 activates enhancer RNA (eRNA) expression, alters histone modification, and increases the enrichment of p300 and RNA Pol II at the enhancer locus. Our results demonstrate a novel mechanism of miRNA as an enhancer trigger. PMID- 26853708 TI - Cationic gadolinium chelate for magnetic resonance imaging of cartilaginous defects. AB - The ability to detect meniscus defects by magnetic resonance arthrography (MRA) can be highly variable. To improve the delineation of fine tears, we synthesized a cationic gadolinium complex, (Gd-DOTA-AM4 )(2+) , that can electrostatically interact with Glycosaminoglycans (GAGs). The complex has a longitudinal relaxivity (r1) of 4.2 mM(-1) s(-1) and is highly stable in serum. Its efficacy in highlighting soft tissue tears was evaluated in comparison to a clinically employed contrast agent (Magnevist) using explants obtained from adult bovine menisci. In all cases, Gd-DOTA-AM4 appeared to improve the ability to detect the soft tissue defect by providing increased signal intensity along the length of the tear. Magnevist shows a strong signal near the liquid-meniscus interface, but much less contrast is observed within the defect at greater depths. This provides initial evidence that cationic contrast agents can be used to improve the diagnostic accuracy of MRA. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26853709 TI - How we think they see us? Valence and difficulty of retrieval as moderators of the effect of meta-stereotype activation on intergroup orientations. AB - Previous research indicates that meta-stereotypes are predominantly negative. However, the valence of the meta-stereotypes may not be the only factor accounting for the detrimental effects associated with their activation. In addition to valence, we propose that the subjective difficulty of retrieving the meta-stereotype might critically determine whether its activation deteriorates intergroup orientations. An experimental study showed that the effect of the meta stereotype activation on the desire to interact with outgroup members was moderated by the interaction between the valence of the meta-stereotype and its difficulty of retrieval. In particular, the activation of a positive meta stereotype deteriorated intergroup orientations when the difficulty of retrieval was high as compared with a condition in which the difficulty of retrieval was low. In sharp contrast, the activation of a negative meta-stereotype worsened intergroup orientations when the difficulty of retrieval was low as compared with a condition in which the difficulty of retrieval was high. PMID- 26853710 TI - Childhood Attention-Deficit/Hyperactivity Disorder, Sex, and Obesity: A Longitudinal Population-Based Study. AB - OBJECTIVE: To assess obesity rates during childhood and young adulthood in patients with attention-deficit/hyperactivity disorder (ADHD) and age- and sex matched controls derived from a population-based birth cohort because cross sectional studies suggest an association between ADHD and obesity. PATIENTS AND METHODS: Study subjects included patients with childhood ADHD (n=336) and age- and sex-matched non-ADHD controls (n=665) from a 1976 to 1982 birth cohort (N=5718). Height, weight, and stimulant treatment measurements were abstracted retrospectively from medical records documenting care provided from January 1, 1976, through August 31, 2010. The association between ADHD and obesity in patients with ADHD relative to controls was estimated using Cox models. RESULTS: Patients with attention-deficit/hyperactivity disorder were 1.23 (95% CI, 1.00 1.50; P<.05) times more likely to be obese during the follow-up period than were non-ADHD controls. This association was not statistically significant in either sex (female participants: hazard ratio [HR], 1.49; 95% CI, 0.98-2.27; P=.06; male participants HR, 1.17, 95% CI, 0.92-1.48; P=.20). Patients with ADHD who were not obese as of the date ADHD research diagnostic criteria were met were 1.56 (95% CI, 1.14-2.13; P<.01) times more likely to be obese during the subsequent follow up than were controls. This association was statistically significant in female study subjects (HR, 2.02; 95% CI, 1.13-3.60; P=.02), but not in male participants (HR, 1.41; 95% CI, 0.97-2.05; P=.07). A higher proportion of patients with ADHD were obese after the age of 20 years compared with non-ADHD controls (34.4% vs 25.1%; P=.01); this difference was observed only in female patients (41.6% vs 19.2%). There were no differences in obesity rates between stimulant-treated and nontreated patients with ADHD. CONCLUSION: Childhood ADHD is associated with obesity during childhood and young adulthood in females. Treatment with stimulant medications is not associated with the development of obesity up to young adulthood. PMID- 26853711 TI - Direct comparison of liquid-based and smear-based cytology with and without rapid on-site evaluation for fine needle aspirates of thoracic tumors. AB - BACKGROUND: Liquid-based cytology (LBC) and rapid on-site evaluation (ROSE) are proposed to improve the quality of fine needle aspirates (FNA) and their diagnostic yield compared with conventional smear cytology (CSC). This prospective study directly compared outcomes of sonar-guided FNA of thoracic tumors supported by LBC, CSC, or CSC with ROSE. METHODS: Three aspirates each for both LBC and CSC with separate 22G spinal needles in a randomized, alternating sequence during 64 transthoracic FNA of thoracic tumors were collected. Smears were prepared by cytology staff on site but evaluated with ROSE only when all six samples had been collected. If no diagnostic material was found on the first three CSC additional needle passes guided by ROSE were performed. RESULTS: Final diagnoses were non-small cell lung cancer in 50 (78.1%), small cell lung cancer in 11 (17.2%), mesothelioma in 1 (1.6%), and inflammation in 2 cases (3.1%), respectively. LBC and CSC were diagnostic in 42 (65.6%) and 49 (76.6%) cases, respectively (P = 0.039), with both methods diagnostic in 41 cases (64.1%). Fifteen cases (23.4%) remained undiagnosed following three passes for CSC but 9 (14.1%) of these were diagnosed using FNA and ROSE with a total yield of 58 cases (90.6%; P < 0.001). CONCLUSION: The diagnostic yield of transthoracic FNA submitted for LBC is significantly lower than with CSC when slides are prepared professionally. ROSE significantly increases the yield of transthoracic FNA. PMID- 26853713 TI - Frequency of HLA-DRB1 and HLA-DQB1 Alleles and Haplotype Association in Syrian Population. AB - The study of Human Leukocyte Antigen (HLA) system is very important in health and diseases. As the HLA loci are the most polymorphic in the human genome, it plays a very important role in the immune responses to self and nonself antigens. In the light of the growing importance of typing the HLA alleles in transplantation, autoimmune diseases, cancer, and many other diseases, we studied 225 unrelated healthy Syrian subjects for their HLA class II genotypes in an attempt to reveal the distribution of the HLA (DRB1-DQB1) alleles in the general Syrian population. Our results revealed that the most common alleles for the DRB1 locus were DRB1*11 (26.4%), DRB1*04 (14%), and DRB1*07 (12%). However, the most frequent alleles for the DQB1 locus were DQB1*03 (40.9%) and DQB1*05 (25.1%). The frequent of two locus haplotypes carry the most frequent alleles at these loci. The most frequently detected class II ''haplotypes'' are DRB1*11-DQB1*03 (8.9%), DRB1*01 DQB1*05 (3.6%), and DRB1*04-DQB1*03 (2.7%). Compared with other populations, our result, deduced from the analysis of genetic distances and the construction of neighbor-joining (NJ) dendrogram, and principal component analysis (PCA) indicates that Syrians are related to Middle Eastern populations. Our data about the Syrian population will aid researchers in studying the relation of HLA class II with different diseases in a Syrian population and will add to the available international literature associated with these loci. PMID- 26853714 TI - Toxigenic Corynebacterium ulcerans isolated from a hunting dog and its diphtheria toxin antibody titer. AB - Toxigenic Corynebacterium ulcerans is a zoonotic pathogen that produces diphtheria toxin and causes a diphtheria-like illness in humans. The organism is known to infect and circulate among dogs, which can then transmit it to humans. Furthermore, previous studies have found that C. ulcerans is carried by wild animals, including game animals. In the present study, we tested hunting and companion dogs for the presence of toxigenic C. ulcerans and succeeded in isolating the bacterium from a hunting dog. Moreover, several hunting dogs had serum diphtheria antitoxin titers that were higher than the titers required for protection in humans, suggesting a history of exposure to toxigenic Corynebacterium strains. Notably, ribotyping, pulsed-field gel electrophoresis and tox gene sequencing demonstrated that the isolate from the hunting dog clustered with previously characterized C. ulcerans strains isolated from wild animals, as opposed to groups of isolates from humans and companion dogs. Interestingly, the wild animal cluster also contains an isolate from an outdoor breeding dog, which could have formed a bridge between isolates from wild animals and those from companion dogs. The results presented herein provide insight into the mechanism by which the zoonotic pathogen C. ulcerans circulates among wild animals, hunting and companion dogs, and humans. PMID- 26853715 TI - When virulence originates from nonagricultural hosts: evolutionary and epidemiological consequences of introgressions following secondary contacts in Venturia inaequalis. AB - In pathogens, introgressions through secondary contacts between divergent populations from agricultural and nonagricultural disease reservoirs are expected to have crucial evolutionary and epidemiological implications. Despite the importance of this question for disease management, experimental demonstrations of these implications remain scarce. Recently, we identified a virulent population of the apple scab pathogen Venturia inaequalis that migrated from nonagricultural hosts to European domestic apple orchards. Here, we investigated the occurrence of gene flow between agricultural and nonagricultural populations sampled in two orchards, and thereafter its consequences on the pathogenicity of hybrids. Population genetic structure and demographic inferences based on the genotypes of 104 strains revealed a high amount of gene flow between the two populations in one orchard. In this site, mating between populations was made possible by the presence of a common host. Our results revealed an invasion of the virulent trait in the agricultural population; a main direction of introgression in hybrids from the agricultural to nonagricultural genetic backgrounds; and a population of hybrids with transgressive traits. We demonstrate a secondary contact with gene flow between divergent populations of pathogens. Our findings highlight evolutionary and epidemiological changes in pathogens and have concrete implications for sustainable disease management. PMID- 26853716 TI - On the use of structured light in nonlinear optics studies of the symmetry group of a crystal. AB - We put forward a technique that allows to extract information about the symmetry group to which certain nonlinear crystals belong using a single illuminating beam. It provides such information by considering the outcome of a nonlinear optics process characterized by the electric nonlinear susceptibility tensor, whose structure is dictated by such symmetry group. As an example, we consider the process of spontaneous parametric down-conversion, when it is pumped with a special type of Bessel beam. The observation of the spatial angular dependence of the lower-frequency generated light provides direct information about the symmetry group of the crystal. We should stress that the choice of the appropriate illumination is of paramount importance for unveiling the sought after information. PMID- 26853712 TI - Genome-wide association study identifies multiple susceptibility loci for craniofacial microsomia. AB - Craniofacial microsomia (CFM) is a rare congenital anomaly that involves immature derivatives from the first and second pharyngeal arches. The genetic pathogenesis of CFM is still unclear. Here we interrogate 0.9 million genetic variants in 939 CFM cases and 2,012 controls from China. After genotyping of an additional 443 cases and 1,669 controls, we identify 8 significantly associated loci with the most significant SNP rs13089920 (logistic regression P=2.15 * 10(-120)) and 5 suggestive loci. The above 13 associated loci, harboured by candidates of ROBO1, GATA3, GBX2, FGF3, NRP2, EDNRB, SHROOM3, SEMA7A, PLCD3, KLF12 and EPAS1, are found to be enriched for genes involved in neural crest cell (NCC) development and vasculogenesis. We then perform whole-genome sequencing on 21 samples from the case cohort, and identify several novel loss-of-function mutations within the associated loci. Our results provide new insights into genetic background of craniofacial microsomia. PMID- 26853717 TI - What's next for hepatitis C virus research? PMID- 26853718 TI - Assessment of the impact of scheduled postmarketing safety summary analyses on regulatory actions. AB - In addition to standard postmarketing drug safety monitoring, Section 915 of the Food and Drug Administration Amendments Act of 2007 (FDAAA) requires the US Food and Drug Administration (FDA) to conduct a summary analysis of adverse event reports to identify risks of a drug or biologic product 18 months after product approval, or after 10,000 patients have used the product, whichever is later. We assessed the extent to which these analyses identified new safety signals and resultant safety-related label changes. Among 458 newly approved products, 300 were the subjects of a scheduled analysis; a new safety signal that resulted in a safety-related label change was found for 11 of these products. Less than 2% of 713 safety-related label changes were based on the scheduled analyses. Our study suggests that the safety summary analyses provide only marginal value over other pharmacovigilance activities. PMID- 26853719 TI - Impact of Culprit Plaque and Atherothrombotic Components on Incomplete Stent Apposition in Patients With ST-Elevation Myocardial Infarction Treated With Everolimus-Eluting Stents - An OCTAVIA Substudy. AB - BACKGROUND: The role of culprit plaque and related atherothrombotic components on incomplete stent apposition (ISA) occurrence after primary percutaneous coronary intervention (p-PCI) is unknown. METHODS AND RESULTS: ST-segment elevation myocardial infarction (STEMI) patients undergoing p-PCI with an everolimus eluting stent were prospectively investigated with optical coherence tomography (OCT) of the infarct-related artery before, after stenting and at 9 months. OCT data, aspirated thrombus and serum inflammatory biomarkers were analyzed. 114 patients with 114 lesions were evaluated. Acute ISA occurred in 82 lesions (71.9%), preferentially in larger vessels with a median area of 0.2 mm(2). The presence of thrombus before stent implantation (odds ratio (OR) 5.5, 95% confidence interval (CI) [1.1-26.9], P=0.04) and the lipid content in the target segment (OR 1.3, 95% CI [1.0-1.5], P=0.04) independently predicted acute ISA. At 9-month follow-up, ISA persisted in 46 lesions (56.1%). The volume of acute ISA significantly predicted persistent ISA (OR 1.3, 95% CI [1.1-1.5], P=0.01). Late acquired ISA occurred in 39 lesions (34.2%) with a median area of 0.3 mm(2). Red/mixed thrombus before stent implantation (OR 3.7, 95% CI [1.0-13.3], P=0.05) and length of the underlying ruptured plaque (OR 1.7, 95% CI [1.1-2.8] P=0.02) were independently associated with late-acquired ISA. CONCLUSIONS: In STEMI patients, culprit plaque and atherothrombotic components of the infarct-related artery significantly contribute to the onset of acute and late ISA. ISA persistence at follow-up depends on the initial volume of acute ISA. PMID- 26853720 TI - Is Extracorporeal Membrane Oxygenator a New Weapon to Improve Prognosis in Patients With Profound Cardiogenic Shock Undergoing Primary Percutaneous Coronary Intervention? AB - Despite advancements in pharmacological therapy and refinement of the tools and technique of primary percutaneous coronary intervention (PCI) and coronary artery bypass surgery, patients with acute myocardial infarction (AMI) complicated by profound cardiogenic shock (CS) still have unacceptably high in-hospital mortality and unfavorable long-term outcome. Thus, there is an imminent need of a new and safe treatment modality in the management of AMI complicated by profound CS. Growing evidence suggests that extracorporeal membrane oxygenator (ECMO) supported primary PCI is an effective therapeutic option for saving lives under such conditions. In this review, we describe and interpret the potential role of circulatory mechanical support by ECMO in the setting of AMI complicated by profound CS for improving clinical outcomes. (Circ J 2016; 80: 572-578). PMID- 26853721 TI - Ultra-High-Definition Mapping of Atrial Arrhythmias. AB - The advantages of ultra-high-definition (UHD) mapping are presented in the context of different atrial arrhythmias, whether focal or macroreentrant. Not only are these sophisticated systems time-saving, but they also allow accurate identification of the substrate (scar quantification), as well as a more precise characterization of the critical isthmuses or focal sources of the atrial circuits. UHD mapping may become a standard approach for their curative treatment. This new technology allows automatic acquisition and accurate annotation of the electrograms, without the need for manual correction. Owing to better resolution, critical isthmuses and low-voltage regions of interest may now be successfully targeted without the need for entrainment maneuvers. Finally, the system also allows rapid assessment of the completeness of the lesions once delivered. (Circ J 2016; 80: 579-586). PMID- 26853722 TI - Colonic Fermentation Promotes Decompression sickness in Rats. AB - Massive bubble formation after diving can lead to decompression sickness (DCS). During dives with hydrogen as a diluent for oxygen, decreasing the body's H2 burden by inoculating hydrogen-metabolizing microbes into the gut reduces the risk of DCS. So we set out to investigate if colonic fermentation leading to endogenous hydrogen production promotes DCS in fasting rats. Four hours before an experimental dive, 93 fasting rats were force-fed, half of them with mannitol and the other half with water. Exhaled hydrogen was measured before and after force feeding. Following the hyperbaric exposure, we looked for signs of DCS. A higher incidence of DCS was found in rats force-fed with mannitol than in those force fed with water (80%, [95%CI 56, 94] versus 40%, [95%CI 19, 64], p < 0.01). In rats force-fed with mannitol, metronidazole pretreatment reduced the incidence of DCS (33%, [95%CI 15, 57], p = 0.005) at the same time as it inhibited colonic fermentation (14 +/- 35 ppm versus 118 +/- 90 ppm, p = 0.0001). Pre-diveingestion of mannitol increased the incidence of DCS in fasting rats when colonic fermentation peaked during the decompression phase. More generally, colonic fermentation in rats on a normal diet could promote DCS through endogenous hydrogen production. PMID- 26853723 TI - Trans-presentation of interleukin-15 by interleukin-15 receptor alpha is dispensable for the pathogenesis of autoimmune type 1 diabetes. AB - Interleukin-15 (IL-15) is a pro-inflammatory cytokine that is required for the survival and activation of memory CD8+T cells, natural killer (NK) cells, innate lymphoid cells, macrophages and dendritic cells. IL-15 is implicated in the pathogenesis of various autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease, psoriasis and autoimmune type 1 diabetes (T1D). IL-15 receptor (IL-15R) consists of a specific alpha chain, the beta chain that is shared with IL-2R and the common gamma chain. IL-15 is unique in the manner in which it binds and signals through its receptor subunits. IL-15 that is complexed with IL-15Ralpha binds to the betagamma receptor complex present on the responding cell to mediate its biological effects through a process referred to as trans-presentation. The trans-presented IL-15 is essential to mediate the biological effects on T lymphocytes and NK cells. Here we show that IL-15, but not IL-15Ralpha, is required for the development of spontaneous and virus-induced T1D, viral clearance and for antigen cross-presentation to CD8+ T lymphocytes. Our findings provide insight into the complexities of IL-15 signalling in the initiation and maintenance of CD8+ T cell-mediated immune responses. PMID- 26853724 TI - Effects of high-fat diet-induced obesity and diabetes on Kiss1 and GPR54 expression in the hypothalamic-pituitary-gonadal (HPG) axis and peripheral organs (fat, pancreas and liver) in male rats. AB - Recent data indicates that kisspeptin, encoded by the KISS1 gene, could play a role in transducing metabolic information into the hypothalamic-pituitary-gonadal (HPG) axis, the mechanism that controls reproductive functions. Numerous studies have shown that in a state of negative energy balance, the hypothalamic kisspeptin system is impaired. However, data concerning positive energy balance (e.g. diabetes and obesity) and the role of kisspeptin in the peripheral tissues is scant. We hypothesized that: 1) in diet-induced obese (DIO) male rats and/or rats with diabetes type 1 (DM1) and type 2 (DM2), altered reproductive functions are related to an imbalance in Kiss1 and GPR54 mRNA in the HPG axis; and 2) in DIO and/or DM1 and/or DM2 rats, Kiss1 and GPR 54 expression are altered in the peripheral tissues involved in metabolic functions (fat, pancreas and liver). Animals were fed a high-fat or control diets and STZ (streptozotocin - toxin, which destroys the pancreas) was injected in high or low doses to induce diabetes type 1 (DM1) or diabetes type 2 (DM2), respectively. RT-PCR and Western blot techniques were used to assess the expression of Kiss1 and GRP54 in tissues. At the level of mRNA, we found that diabetic but not obese rats have alterations in Kiss1 and/or GPR54 mRNA levels in the HPG axis as well as in peripheral tissues involved in metabolic functions (fat, pancreas and liver). The most severe changes were seen in DM1 rats. However, in the case of protein levels in the peripheral tissues (fat, pancreas and liver), changes in Kiss1/GPR54 expression were noticed in DIO, DM1 and DM2 animals and were tissue-specific. Our data support the hypothesis that alterations in Kiss1/GPR54 balance may account for both reproductive and metabolic abnormalities reported in obese and diabetic rats. PMID- 26853725 TI - [Bexsero, a novel vaccine against meningococcus]. AB - Meningococcus B is the most prevalent Neisseria meningitidis serogroup isolated in Hungary. Bexsero is one of the vaccines developed against it, which has been available in Hungary since the summer of 2014. The authors summarize the most important issues and open questions concerning the disease and the vaccine based on literature review. Based on immunological evidence, it is expected that Bexsero provides protection against this rare but very serious infection. However, the vaccine is extremely expensive, the clinical effectiveness has not yet been proven and it frequently causes fever, especially in infants where the vaccine is most needed. According to the opinion of the authors, the formulation of a Hungarian guideline concerning the application of Bexsero should be postponed until the accumulating international experience makes it possible to better judge the vaccine's benefits, risks and cost-effectiveness. For patients with asplenia, complement defect or other immunological defect, or in case of markedly increased individual risk of contracting the disease, the vaccination is already justified. PMID- 26853726 TI - [Comparison of treatment principles of elderly hypertensive patients with different cardiovascular risks based on Hungarian and international guidelines (2001-2015)]. AB - The aim of this review is to present recommendations of the currently valid Hungarian practice guidelines regarding antihypertensive therapy of the elderly and very elderly with different cardiovascular risk profiles, compare and contrast these with international guidelines, describe changes brought about by the past 15 years, and review the evidence behind. Hypertension treatment guidelines and relevant statements of the Hungarian and European Societies of Hypertension, of the Joint National Committee and American Heart Association were processed. The use of age-independent treatment threshold, goal blood pressure values, and the tendency towards more intensive control in co-morbidities conferring high cardiovascular risk were overcome by the upsurge of new evidence and the re-evaluation of previous clinical trial data. These lead to the introduction of age-specific and generally less stringent blood pressure targets in all regions compared. However, the guidelines currently in force still differ in terms of the attainable values in concomitant diabetes, chronic kidney disease or albuminuria, use of beta-blockers and the definition of elderly. Nevertheless, there is unanimous agreement that benefit from lowering of blood pressure under systolic 140 mmHg is not supported by evidence and further investigation is warranted to determine optimal treatment targets in the elderly, in the aged over 80 and specific elderly risk groups. PMID- 26853727 TI - [Options for stress management in obesity treatment]. AB - Overeating and physical inactivity are of great importance in the etiology of obesity. Psychological factors are often found in the background of life style. Chronic stress can contribute to physical inactivity and behaviors that hinder the keeping of a diet (e.g., irregular eating pattern, emotional eating). Results of randomized controlled trials show that relaxation can reduce emotional eating, improve cognitive restraint, and thereby reduce weight. However, stress management is more than relaxation. It consists of adaptive emotion-focused and problem-focused coping strategies and skills to improve relationships. Deflection skills may help in replacing emotional eating with other behaviors. Cognitive restructuring, saying no, and problem solving help to prevent or manage conflicts and difficulties otherwise would result in overeating due to distress. Developing stress management skills may result in greater compliance with the treatment. The techniques presented in the study can be easily applied by general practitioners or specialists, and provide tools for optimizing obesity treatment. PMID- 26853728 TI - [Cost-effectiveness trial of self-expandable metal stents and plastic biliary stents in malignant biliary obstruction]. AB - INTRODUCTION: Self-expandable metal and plastic stents can be applied in the palliative endoscopic treatment of patients with unresectable malignant biliary obstruction. The use of metal stentsis recommended if the patient's life expectancy is more than four months. AIM: To compare the therapeutic efficacy and cost-effectiveness of metal and plastic stents in the treatment of malignant biliary obstruction. METHOD: The authors retrospectively enrolled patients who received metal (37 patients) or plastic stent (37 patients). The complication rate, stent patency and cumulative cost of treatment were assessed in the two groups. RESULTS: The complication rate of metal stents was lower (37.84% vs. 56.76%), but the stent patency was higher compared with plastic stents (19.11 vs. 8.29 weeks; p = 0.0041). In the plastic stent group the frequency of hospitalization of patients in context with stent complications (1.18 vs. 2.32; p = 0.05) and the necessity of reintervention for stent dysfunction (17 vs. 27; p = 0.033) were substantially higher. In this group multiple stent implantation raised the stent patency from 7.68 to 10.75 weeks. There was no difference in the total cost of treatment of malignant biliary obstruction between the two groups (p = 0.848). CONCLUSIONS: Considering the cost of treatment and the burden of patients the authors recommend self-expandable metal sten timplantation if the life expectancy of patients is more than two months. In short survival cases multiple plastic stent implantation is recommended. PMID- 26853729 TI - [A rare case of thermoregulation disorder: Shapiro syndrome]. AB - Anomalies of the corpus callosum are the most frequent malformations of the central nervous system. The triad of spontaneous periodic hypothermia and hyperhydrosis with the agenesis of corpus callosum is described as Shapiro syndrome. Shapiro syndrome is a very rare condition and it can occur in every age group. The presence of agenesis of corpus callosum is not a strict criteria of the syndrome; the most important presenting symptom is paroxysmal hypothermia. Although the definite cause of recurrent hypothermia is unknown, dysfunction of the hypothalamus is suspected. From therapeutic aspects, only supportive therapy is available. In this report the authors present the first Shapiro syndrome case diagnosed in Hungary. The main symptoms of the 21-year-old male patient were recurrent hyperhydrosis with hypothermia resulting in severe general malaise. The skull magnetic resonance imaging demonstrated agenesis of corpus callosum. The patient was treated with clonidine resulting in significant improvement of symptoms. PMID- 26853731 TI - Dialectal and gender differences in nasalance for a Mandarin population. AB - The purpose of this study was to determine whether there are dialectal and gender related differences in nasalance of main Mandarin vowels and three sentences in 400 Chinese normal adults. The mean nasalance score difference for dialect and gender was significant (p < .001) in all speech materials. For different dialects, the average nasalance scores show that Chongqing > Beijing > Shanghai > Guangzhou for the nasal sentence, oro-nasal sentence, /a/, /i/ and /u/. In addition, the average nasalance scores of females were higher than those of males for all speech materials in all dialects. The clinical significance of this study can be helpful in making nasalance clinical decisions for Chinese people with cleft palate, hearing disorders and dysarthria with resonance disorders. It also shows the theoretical and socio-cultural features for linguists considering dialects and gender. PMID- 26853732 TI - A Simple low-cost device enables four epi-illumination techniques on standard light microscopes. AB - Back-scattering darkfield (BSDF), epi-fluorescence (EF), interference reflection contrast (IRC), and darkfield surface reflection (DFSR) are advanced but expensive light microscopy techniques with limited availability. Here we show a simple optical design that combines these four techniques in a simple low-cost miniature epi-illuminator, which inserts into the differential interference contrast (DIC) slider bay of a commercial microscope, without further additions required. We demonstrate with this device: 1) BSDF-based detection of Malarial parasites inside unstained human erythrocytes; 2) EF imaging with and without dichroic components, including detection of DAPI-stained Leishmania parasite without using excitation or emission filters; 3) RIC of black lipid membranes and other thin films, and 4) DFSR of patterned opaque and transparent surfaces. We believe that our design can expand the functionality of commercial bright field microscopes, provide easy field detection of parasites and be of interest to many users of light microscopy. PMID- 26853733 TI - A TTC threshold for acute oral exposure to non-genotoxic substances. AB - To derive an acute TTC threshold, the correlation between Allowable Daily Intakes (ADIs, chronic values) and Acute Reference Doses (ARfDs) of pesticides evaluated in the EU was investigated and their distributions were compared. The correlation between ARfDs and ADIs was significant (p = 0.01), but weak (r(2) = 0.051). Consequently, using this approach to derive acute TTC values does not seem valid. Therefore, the distributions of ARfDs and ADIs were compared directly, in order to extrapolate from chronic to acute TTC values. This comparison made for the combined Cramer structural class II and III pesticides showed a ratio ARfD/ADI of approximately 3 at the fifth percentile of the distributions. Based on these results, it is justified to propose a TTC for acute effects for Cramer III substances by multiplying the Cramer class III TTC threshold of 90 MUg/person/day with a factor 3. This leads to an acute TTC threshold based on the Munro dataset for Cramer class III substances of 270 MUg/person/day. PMID- 26853734 TI - Additive effect of BLA GABAA receptor mechanism and (+)-MK-801 on memory retention deficit, an isobologram analysis. AB - There is a near correlation between N-methyl-d-aspartate (NMDA) and gamma aminobutyric acid (GABA) receptors in the modulation of learning and memory in the basolateral amygdala (BLA). In this study, we investigated the involvement of GABAA receptors in the BLA in amnesia induced by (+)-MK-801, a noncompetitive antagonist of NMDA receptors, in male Wistar rats. After guide cannulae were bilaterally placed in the BLA, animals were trained in a step-through type passive avoidance task and then tested 24h after training to measure memory retrieval and locomotor activity. Post-training intra-BLA microinjection of (+) MK-801 (0.5 MUg/rat) and GABAA receptor agonists (muscimol at doses 0.05 and 0.1 MUg/rat) or antagonist (bicuculline at doses 0.05 and 0.1 MUg/rat) decreased step through latency during retrieval but did not alter locomotor activity. Results also showed that a subthreshold dose of muscimol (0.025 MUg/rat) potentiated impairment induced by (+)-MK-801, whereas bicuculline (0.025 MUg/rat) restored it. Furthermore, the highest dose of muscimol (0.5 MUg/rat) increased locomotor activity induced by (+)-MK-801. Isobologram analysis showed that there was an additive but not synergistic effect between muscimol and (+)-MK-801 on memory retention deficits in the BLA. In conclusion, muscimol and bicuculline decreased retention of memory formation in the BLA, and GABAA receptors in the BLA may be involved in the additive effect on (+)-MK-801-induced memory retention deficits. PMID- 26853735 TI - Epidermal changes during UVB phototherapy assessed by multiphoton laser tomography. AB - BACKGROUND: Multiphoton laser tomography (MPT) is a non-invasive technique that allows imaging of skin in vivo with very high spatial resolution and contrast. Previous work of our group has demonstrated that known morphological changes due to erythematogenic ultraviolet B (UVB) irradiation may be imaged in vivo by MPT. The present work investigated if morphological skin changes known from experimental erythematogenic UVB irradiation are also demonstrable in the course of a standard phototherapy regime that implies suberythematogenic doses of narrow band UVB. METHODS: Sixteen patients with psoriasis vulgaris receiving a narrow band phototherapy were included. A test field and a light-protected control field were measured with the multiphoton tomograph DermaInspect(r) at four time points: at baseline, the next day, after 3 days and at the day of the last exposure. RESULTS: In the course of the UVB phototherapy, spongiosis and pleomorphy as parameters of inflammation and cellular damage did not show significant changes. By contrast, an adaptive skin reaction with significant changes of keratosis and pigmentation was observed. CONCLUSION: MPT is a suitable technique for the investigation of qualitative and quantitative skin changes after UVB irradiation. After suberythematogenic UVB irradiation, photoadaptive skin changes, but no cellular damage can be observed with MPT. PMID- 26853736 TI - Occupational physical activity assessment for chronic disease prevention and management: A review of methods for both occupational health practitioners and researchers. AB - Occupational physical activity (OPA) is an occupational exposure that impacts worker health. OPA is amenable to measurement and modification through the hierarchy of controls. Occupational exposure scientists have roles in addressing inadequate physical activity, as well as excessive or harmful physical activity. Occupational health researchers can contribute to the development of novel OPA exposure assessment techniques and to epidemiologic studies examining the health impacts of physical activity at work. Occupational health practitioners stand to benefit from understanding the strengths and limitations of physical activity measurement approaches, such as accelerometers in smartphones, which are already ubiquitous in many workplaces and in some worksite health programs. This comprehensive review of the literature provides an overview of physical activity monitoring for occupational exposure scientists. This article summarizes data on the public health implications of physical activity at work, highlighting complex relationships with common chronic diseases. This article includes descriptions of several techniques that have been used to measure physical activity at work and elsewhere, focusing in detail on pedometers, accelerometers, and Global Positioning System technology. Additional subjective and objective measurement strategies are described as well. PMID- 26853737 TI - Reward anticipation and trait anhedonia: An electrophysiological investigation in subjects with schizophrenia. AB - OBJECTIVE: Investigate impairment of reward anticipation in subjects with schizophrenia (SCZ) and its association with negative symptom dimensions and hedonic experience. METHODS: Event-related potentials (ERPs) were recorded, in thirty SCZ and twenty-three matched healthy controls (HC), during a "Monetary Incentive Delay" task in which reward and loss cues (incentive cues of positive and negative value) of different magnitude, as well as neutral cues were presented. ASSESSMENTS: anticipatory and consummatory pleasure, trait anhedonia and motivation in all subjects; avolition and expressive deficit in SCZ. RESULTS: SCZ had lower motivation but comparable hedonic experience with respect to HC. In HC, during reward anticipation, the early P3 was larger for large magnitude incentives, irrespective of their valence, while the late P3 was larger for large reward. In SCZ, early P3 did not discriminate the incentive magnitude and the late P3 was larger for large loss. Early P3 amplitude for large magnitude incentives was inversely related to trait social anhedonia but not to negative symptoms dimensions. CONCLUSIONS: SCZ are unable to integrate the incentive magnitude and reward value of future events in the context of their ongoing task. P3 abnormalities are associated with trait anhedonia, but not with negative symptoms dimensions. SIGNIFICANCE: In line with recent studies, our findings indicate that anhedonia and avolition are partially independent constructs. PMID- 26853738 TI - Oriented Nucleation of both Ge-Fresnoite and Benitoite/BaGe4O9 during the Surface Crystallisation of Glass Studied by Electron Backscatter Diffraction. AB - Two glasses of the compositions 2 BaO - TiO2 - 2.75 GeO2 and 2 BaO - TiO2 -3.67 GeO2 (also known as BTG55) are annealed at temperatures from 680 to 970 degrees C to induce surface crystallization. The resulting samples are analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM) including electron backscatter diffraction (EBSD). Ge-Fresnoite (Ba2TiGe2O8, BTG) is observed at the immediate surface of all samples and oriented nucleation is proven in both compositions. After a very fast kinetic selection, the crystal growth of BTG into the bulk occurs via highly oriented dendrites where the c-axes are oriented perpendicular to the surface. The growth of this oriented layer is finally blocked by dendritc BTG originating from bulk nucleation. The secondary phases BaTiGe3O9 (benitoite) and BaGe4O9 are also identified near the surface by XRD and localized by EBSD which additionally indicates orientation preferences for these phases. This behaviour is in contrast with previous reports from the Ba2TiSi2O8 as well as the Sr2TiSi2O8 systems. PMID- 26853739 TI - A Mechanistic Study of Halogen Addition and Photoelimination from pi-Conjugated Tellurophenes. AB - The ability to drive reactivity using visible light is of importance for many disciplines of chemistry and has significant implications for sustainable chemistry. Identifying photochemically active compounds and understanding photochemical mechanisms is important for the development of useful materials for synthesis and catalysis. Here we report a series of photoactive diphenyltellurophene compounds bearing electron-withdrawing and electron-donating substituents synthesized by alkyne coupling/ring closing or palladium-catalyzed ipso-arylation chemistry. The redox chemistry of these compounds was studied with respect to oxidative addition and photoelimination of bromine, which is of importance for energy storage reactions involving X2. The oxidative addition reaction mechanism was studied using density functional theory, the results of which support a three-step mechanism involving the formation of an initial eta(1) association complex, a monobrominated intermediate, and finally the dibrominated product. All of the tellurophene derivatives undergo photoreduction using 430, 447, or 617 nm light depending on the absorption properties of the compound. Compounds bearing electron-withdrawing substituents have the highest photochemical quantum efficiencies in the presence of an alkene trap, with efficiencies of up to 42.4% for a pentafluorophenyl-functionalized tellurophene. The photoelimination reaction was studied in detail through bromine trapping experiments and laser flash photolysis, and a mechanism is proposed. The photoreaction, which occurs by release of bromine radicals, is competitive with intersystem crossing to the triplet state of the brominated species, as evidenced by the formation of singlet oxygen. These findings should be useful for the design of new photochemically active compounds supported by main-group elements. PMID- 26853740 TI - A lateralized anterior flange improves femoral component bone coverage in current total knee prostheses. AB - BACKGROUND: Poor femoral implant fit to resected bone surfaces recently has been the motivation for several new total knee arthroplasty implant designs. Implant overhang risks adverse soft-tissue interaction while uncovered cut bone surfaces (underhang) risks increased postoperative bleeding or development of heterotopic bone. METHODS: Femoral implant fit was studied systematically, and without the influence of surgical variation, by virtually implanting standard and narrow width femoral components (Bi-Surface 5) using preoperative computed tomography data for 150 varus osteoarthritic knees in Japanese patients. Overhang and underhang rates and bone widths were determined by gender. RESULTS: Narrow femoral components helped avoid or minimize overhang in most female and some male knees. Although anterior width in the narrow components closely matched female bone width, the femoral component was necessarily displaced laterally to avoid overhang in the anteromedial portion. Consequently, there was significant medial underhang in the distal and posterior zones. CONCLUSIONS: Ideally, the anterior femoral flange should be shifted 2 to 2.5mm laterally relative to the distal and posterior aspects to provide optimal femoral bone coverage in this prosthesis. The current study also confirmed that this modification can be generalized to the other two currently available "narrow type" prostheses. This geometric modification might allow surgeons to select a femoral component with slightly wider mediolateral dimensions in the distal and posterior aspects to minimize underhang, while eliminating anterior overhang. LEVEL OF EVIDENCE: III. PMID- 26853742 TI - Amperometric determination of serum total cholesterol with nanoparticles of cholesterol esterase and cholesterol oxidase. AB - We describe the preparation of glutaraldehyde cross-linked and functionalized cholesterol esterase nanoparticles (ChENPs) and cholesterol oxidase nanoparticles (ChOxNPs) aggregates and their co-immobilization onto Au electrode for improved amperometric determination of serum total cholesterol. Transmission electron microscope (TEM) images of ChENPs and ChOxNPs showed their spherical shape and average size of 35.40 and 56.97 nm, respectively. Scanning electron microscope (SEM) studies of Au electrode confirmed the co-immobilization of enzyme nanoparticles (ENPs). The biosensor exhibited optimal response at pH 5.5 and 40 degrees C within 5 s when polarized at +0.25 V versus Ag/AgCl. The working/linear range of the biosensor was 10-700 mg/dl for cholesterol. The sensor showed high sensitivity and measured total cholesterol as low as 0.1 mg/dl. The biosensor was evaluated and employed for total cholesterol determination in sera of apparently healthy and diseased persons. The analytical recovery of added cholesterol was 90%, whereas the within-batch and between-batch coefficients of variation (CVs) were less than 2% and less than 3%. There was a good correlation (r = 0.99) between serum cholesterol values as measured by the standard enzymic colorimetric method and the current method. The initial activity of ENPs/working electrode was reduced by 50% during its regular use (200 times) over a period of 60 days when stored dry at 4 degrees C. PMID- 26853741 TI - Serological Evaluation of Immunity to the Varicella-Zoster Virus Based on a Novel Competitive Enzyme-Linked Immunosorbent Assay. AB - Varicella-zoster virus (VZV) is a highly contagious agent of varicella and herpes zoster. Varicella can be lethal to immunocompromised patients, babies, HIV patients and other adults with impaired immunity. Serological evaluation of immunity to VZV will help determine which individuals are susceptible and evaluate vaccine effectiveness. A collection of 110 monoclonal antibodies (mAbs) were obtained by immunization of mice with membrane proteins or cell-free virus. The mAbs were well characterized, and a competitive sandwich ELISA (capture mAb: 8H6; labelling mAb: 1B11) was established to determine neutralizing antibodies in human serum with reference to the FAMA test. A total of 920 human sera were evaluated. The competitive sandwich ELISA showed a sensitivity of 95.6%, specificity of 99.77% and coincidence of 97.61% compared with the fluorescent antibody-to-membrane-antigen (FAMA) test. The capture mAb 8H6 was characterized as a specific mAb for VZV ORF9, a membrane-associated tegument protein that interacts with glycoprotein E (gE), glycoprotein B (gB) and glycoprotein C (gC). The labelling mAb 1B11 was characterized as a complement-dependent neutralizing mAb specific for the immune-dominant epitope located on gE, not on other VZV glycoproteins. The established competitive sandwich ELISA could be used as a rapid and high-throughput method for evaluating immunity to VZV. PMID- 26853743 TI - Polymerase chain reaction-hybridization method using urease gene sequences for high-throughput Ureaplasma urealyticum and Ureaplasma parvum detection and differentiation. AB - In this article, we discuss the polymerase chain reaction (PCR)-hybridization assay that we developed for high-throughput simultaneous detection and differentiation of Ureaplasma urealyticum and Ureaplasma parvum using one set of primers and two specific DNA probes based on urease gene nucleotide sequence differences. First, U. urealyticum and U. parvum DNA samples were specifically amplified using one set of biotin-labeled primers. Furthermore, amine-modified DNA probes, which can specifically react with U. urealyticum or U. parvum DNA, were covalently immobilized to a DNA-BIND plate surface. The plate was then incubated with the PCR products to facilitate sequence-specific DNA binding. Horseradish peroxidase-streptavidin conjugation and a colorimetric assay were used. Based on the results, the PCR-hybridization assay we developed can specifically differentiate U. urealyticum and U. parvum with high sensitivity (95%) compared with cultivation (72.5%). Hence, this study demonstrates a new method for high-throughput simultaneous differentiation and detection of U. urealyticum and U. parvum with high sensitivity. Based on these observations, the PCR-hybridization assay developed in this study is ideal for detecting and discriminating U. urealyticum and U. parvum in clinical applications. PMID- 26853744 TI - A simple modification to improve the accuracy of methylation-sensitive restriction enzyme quantitative polymerase chain reaction. AB - DNA digestion with endonucleases sensitive to CpG methylation such as HpaII followed by polymerase chain reaction (PCR) quantitation is commonly used in molecular studies as a simple and inexpensive solution for assessment of region specific DNA methylation. We observed that the results of such analyses were highly overestimated if mock-digested samples were applied as the reference. We determined DNA methylation levels in several promoter regions in two setups implementing different references: mock-digested and treated with a restriction enzyme that has no recognition sites within examined amplicons. Fragmentation of reference templates allowed removing the overestimation effect, thereby improving measurement accuracy. PMID- 26853745 TI - Effects of volatile oils of Angelica sinensis on an acute inflammation rat model. AB - Context Despite several pharmacological studies of volatile oils of Angelica sinensis (Oliv.) Diels (Umbelliferae) (VOAS), its anti-inflammatory mechanism remains unknown. Objective The study investigates the effects of VOAS on the lipopolysaccharide (LPS)-induced acute inflammation rat model and analyzes its possible anti-inflammatory mechanisms. Materials and methods Fourty rats were randomly divided into the control, model, VOAS and dexamethasone (Dex) groups. The VOAS and Dex groups were given VOAS (0.176 mL/kg) and Dex (40 MUg/kg), respectively. Rats in all groups except the control group were intraperitoneally injected with LPS (100 MUg/kg), their exterior behaviour and liver pathological changes were observed, and the level of white blood cell (WBC), the number of neutrophils (NE)%, glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP), tumour necrosis factor (TNF alpha), interleukin (IL)-1beta, IL-6, IL-10, histamine (HIS), 5-hydroxytryptamine (5-HT), nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) were detected. Results Compared with the model group, VOAS and Dex significantly accelerated the recovery of the exterior behaviour, the liver pathological changes of rats, and increased the level of IL-10, but decreased the level of WBC, NE%, GOT, GPT, ALP, TNF-alpha, IL 1beta, IL-6, HIS, 5-HT, NO, PGE2, iNOS and COX-2 (p < 0.05). Conclusion VOAS exhibits anti-inflammatory and liver protection effects by inhibiting the secretion of the pro-inflammatory cytokines (TNF-alpha, IL-1beta and IL-6), the inflammatory mediators (HIS, 5-HT, PGE2 and NO), the inflammation-related enzymes (iNOS and COX-2), as well as promoting the production of the anti-inflammatory cytokines IL-10. PMID- 26853746 TI - Characterization and comparative analysis of 2,4-toluene diisocyanate and 1,6 hexamethylene diisocyanate haptenated human serum albumin and hemoglobin. AB - Diisocyanates (dNCOs) are low molecular weight chemical sensitizers that react with autologous proteins to produce neoantigens. dNCO-haptenated proteins have been used as immunogens for generation of dNCO-specific antibodies and as antigens to screen for dNCO-specific antibodies in exposed individuals. Detection of dNCO-specific antibodies in exposed individuals for diagnosis of dNCO asthma has been hampered by poor sensitivities of the assay methods in that specific IgE can only be detected in approximately 25% of the dNCO asthmatics. Apart from characterization of the conjugates used for these immunoassays, the choice of the carrier protein and the dNCO used are important parameters that can influence the detection of dNCO-specific antibodies. Human serum albumin (HSA) is the most common carrier protein used for detection of dNCO specific-IgE and -IgG but the immunogenicity and/or antigenicity of other proteins that may be modified by dNCO in vivo is not well documented. In the current study, 2,4-toluene diisocyanate (TDI) and 1,6-hexamethylene diisocyanate (HDI) were reacted with HSA and human hemoglobin (Hb) and the resultant adducts were characterized by (i) HPLC quantification of the diamine produced from acid hydrolysis of the adducts, (ii) 2,4,6-trinitrobenzene sulfonic acid (TNBS) assay to assess extent of cross linking, (iii) electrophoretic migration in polyacrylamide gels to analyze intra- and inter-molecular cross-linking, and (iv) evaluation of antigenicity using a monoclonal antibody developed previously to TDI conjugated to Keyhole limpet hemocyanin (KLH). Concentration-dependent increases in the amount of dNCO bound to HDI and TDI, cross-linking, migration in gels, and antibody-binding were observed. TDI reactivity with both HSA and Hb was significantly higher than HDI. Hb-TDI antigenicity was approximately 30% that of HSA-TDI. In conclusion, this data suggests that both, the extent of haptenation as well as the degree of cross linking differs between the two diisocyanate species studied, which may influence their relative immunogenicity and/or antigenicity. PMID- 26853748 TI - The Intestinal Immune System in Obesity and Insulin Resistance. AB - Obesity and insulin resistance are associated with chronic inflammation in metabolic tissues such as adipose tissue and the liver. Recently, growing evidence has implicated the intestinal immune system as an important contributor to metabolic disease. Obesity predisposes to altered intestinal immunity and is associated with changes to the gut microbiota, intestinal barrier function, gut residing innate and adaptive immune cells, and oral tolerance to luminal antigens. Accordingly, the gut immune system may represent a novel therapeutic target for systemic inflammation in insulin resistance. This review discusses the emerging field of intestinal immunity in obesity-related insulin resistance and how it affects metabolic disease. PMID- 26853747 TI - Environment Impacts the Metabolic Dependencies of Ras-Driven Non-Small Cell Lung Cancer. AB - Cultured cells convert glucose to lactate, and glutamine is the major source of tricarboxylic acid (TCA)-cycle carbon, but whether the same metabolic phenotype is found in tumors is less studied. We infused mice with lung cancers with isotope-labeled glucose or glutamine and compared the fate of these nutrients in tumor and normal tissue. As expected, lung tumors exhibit increased lactate production from glucose. However, glutamine utilization by both lung tumors and normal lung was minimal, with lung tumors showing increased glucose contribution to the TCA cycle relative to normal lung tissue. Deletion of enzymes involved in glucose oxidation demonstrates that glucose carbon contribution to the TCA cycle is required for tumor formation. These data suggest that understanding nutrient utilization by tumors can predict metabolic dependencies of cancers in vivo. Furthermore, these data argue that the in vivo environment is an important determinant of the metabolic phenotype of cancer cells. PMID- 26853749 TI - FGF21 Lowers Plasma Triglycerides by Accelerating Lipoprotein Catabolism in White and Brown Adipose Tissues. AB - FGF21 decreases plasma triglycerides (TGs) in rodents and humans; however, the underlying mechanism or mechanisms are unclear. In the present study, we examined the role of FGF21 in production and disposal of TG-rich lipoproteins (TRLs) in mice. Treatment with pharmacological doses of FGF21 acutely reduced plasma non esterified fatty acids (NEFAs), liver TG content, and VLDL-TG secretion. In addition, metabolic turnover studies revealed that FGF21 facilitated the catabolism of TRL in white adipose tissue (WAT) and brown adipose tissue (BAT). FGF21-dependent TRL processing was strongly attenuated in CD36-deficient mice and transgenic mice lacking lipoprotein lipase in adipose tissues. Insulin resistance in diet-induced obese and ob/ob mice shifted FGF21 responses from WAT toward energy-combusting BAT. In conclusion, FGF21 lowers plasma TGs through a dual mechanism: first, by reducing NEFA plasma levels and consequently hepatic VLDL lipidation and, second, by increasing CD36 and LPL-dependent TRL disposal in WAT and BAT. PMID- 26853751 TI - New Therapeutic Approaches to the Treatment of Dyslipidemia. AB - Dyslipidemia is a risk factor for atherosclerotic cardiovascular disease (ASCVD). Abundant data indicate that low-density lipoproteins (LDL) are causal for ASCVD; a new class of LDL-lowering medicines, the PCSK9 inhibitors, will address much unmet medical need. Human genetics suggest that triglyceride-rich lipoproteins (TRL) are pro-atherogenic and have pointed to a number of protein regulators of lipoprotein lipase activity that are candidates for therapeutic targeting. Finally, high-density lipoprotein (HDL) cholesterol does not appear to be causally associated with protection from ASCVD, reinforced by the failure of three CETP inhibitors in CV outcome trials, but HDL function remains of interest. PMID- 26853750 TI - HIF2alpha Is an Essential Molecular Brake for Postprandial Hepatic Glucagon Response Independent of Insulin Signaling. AB - Glucagon drives hepatic gluconeogenesis and maintains blood glucose levels during fasting. The mechanism that attenuates glucagon action following refeeding is not understood. The present study demonstrates an increase in perivenous liver hypoxia immediately after feeding, which stabilizes hypoxia-inducible factor 2alpha (HIF2alpha) in liver. The transient postprandial increase in hepatic HIF2alpha attenuates glucagon signaling. Hepatocyte-specific disruption of HIF2alpha increases postprandial blood glucose and potentiates the glucagon response. Independent of insulin/AKT signaling, activation of hepatic HIF2alpha resulted in lower blood glucose, improved glucose tolerance, and decreased gluconeogenesis due to blunted hepatic glucagon action. Mechanistically, HIF2alpha abrogated glucagon-PKA signaling by activating cAMP-phosphodiesterases in a MEK/ERK-dependent manner. Repression of glucagon signaling by HIF2alpha ameliorated hyperglycemia in streptozotocin-induced diabetes and acute insulin resistant animal models. This study reveals that HIF2alpha is essential for the acute postprandial regulation of hepatic glucagon signaling and suggests HIF2alpha as a potential therapeutic target in the treatment of diabetes. PMID- 26853752 TI - RNA binding proteins regulate anabolic and catabolic gene expression in chondrocytes. AB - OBJECTIVE: Regulation of anabolic and catabolic factors is considered essential in maintaining the homoeostasis of healthy articular cartilage. In this study we investigated the influence of RNA binding proteins (RNABPs) in this process. DESIGN: Using small interfering RNA (siRNA), RNABP expression was knocked down in SW1353 chondrosarcoma cells and human articular chondrocytes. Gene expression and messenger RNA (mRNA) decay of anabolic (SOX9, Aggrecan) and catabolic (matrix metalloproteinase (MMP)13) factors were analysed using reverse transcription quantitative polymerase chain reaction (RT-qPCR). RNA-electromobility shift assays (EMSAs) were used to investigate RNABP interactions with the SOX9 mRNA 3' untranslated region (UTR). Immunohistochemical localisation of MMP13 and the RNABP human antigen R (HuR) was performed in E13.5 and E16.5 mouse embryo sections. RESULTS: SOX9 mRNA, mRNA half-life and protein expression were increased with siRNA targeting the RNABP tristetraprolin (TTP) in both HACs and SW1353s. TTP knockdown also stimulated aggrecan mRNA expression but did not affect its stability. RNA-EMSAs demonstrated that adenine uracil (AU)-rich elements in the SOX9 mRNA 3'UTR interacted with chondrocyte proteins with three specific elements interacting with TTP. HuR knockdown significantly increased MMP13 expression and also regulated the expression of a number of known transcriptional repressors of MMP13. HuR was ubiquitously expressed within mouse embryos yet displayed regional down-regulation within developing skeletal structures. CONCLUSION: This study demonstrates for the first time how RNABPs are able to affect the balance of anabolic and catabolic gene expression in human chondrocytes. The post-transcriptional mechanisms controlled by RNABPs present novel avenues of regulation and potential points of intervention for controlling the expression of SOX9 and MMP13 in chondrocytes. PMID- 26853754 TI - Antibacterial efficacy of rifampin loaded solid lipid nanoparticles against Staphylococcus epidermidis biofilm. AB - OBJECTIVE: The aim of the present study was to assess the in vitro anti-biofilm activities of solid lipid nanoparticles (SLN) loaded with rifampin against biofilm-producing Staphylococcus epidermidis. METHODS: SLN were prepared and characterized for size, zeta potentials and encapsulation efficacy. The morphological and thermal properties of formulation were evaluated by TEM imagining and DSC analysis. The anti-biofilm activity of different formulations was assessed at different incubation times and concentrations by crystal violet (CV) and viable biofilm count methods. RESULTS: The zeta potentials, particle sizes and encapsulation efficiencies of final formulations were 17 +/- 0.7 mV, 101 +/- 4.7 nm and approximately 70%; respectively. Rifampin-SLN was able to reduce the biomass of biofilm at time- and concentration-dependent manner. According to biofilm count results, the Rifampin-SLN was more effective for removal of the bacteria with respect to free rifampin. CONCLUSION: The results of this study highlight the advantages and efficiency of Rifampin-SLN in biofilm eradication. PMID- 26853755 TI - Behaviors of heavy metals (Cd, Cu, Ni, Pb and Zn) in soil amended with composts. AB - This study investigated how amendment with sewage sludge compost of different maturation times (3, 6, 12 months) affected metal (Cd, Cu, Ni, Pb, Zn) bioavailability, fractionation and redistribution in highly contaminated sandy clay soil. Metal transformations during long-term soil stabilization (35 months) were determined. In the contaminated soil, Cd, Ni and Zn were predominately in the exchangeable and reducible fractions, Pb in the reducible fraction and Cu in the reducible, exchangeable and oxidizable fractions. All composts decreased the bioavailability of Cd, Ni and Zn for up to 24 months, which indicates that cyclic amendment with compost is necessary. The bioavailability of Pb and Cu was not affected by compost amendment. Based on the reduced partition index (IR), metal stability in amended soil after 35 months of stabilization was in the following order: Cu > Ni = Pb > Zn > Cd. All composts were more effective in decreasing Cd, Ni and Zn bioavailability than in redistributing the metals, and increasing Cu redistribution more than that of Pb. Thus, sewage sludge compost of as little as 3 months maturation can be used for cyclic amendment of multi-metal-contaminated soil. PMID- 26853753 TI - Gut microbiota and malnutrition. AB - Malnutrition is the leading cause of death worldwide in children under the age of five, and is the focus of the first World Health Organization (WHO) Millennium Development Goal. Breastfeeding, food and water security are major protective factors against malnutrition and critical factors in the maturation of healthy gut microbiota, characterized by a transient bifidobacterial bloom before a global rise in anaerobes. Early depletion in gut Bifidobacterium longum, a typical maternal probiotic, known to inhibit pathogens, represents the first step in gut microbiota alteration associated with severe acute malnutrition (SAM). Later, the absence of the Healthy Mature Anaerobic Gut Microbiota (HMAGM) leads to deficient energy harvest, vitamin biosynthesis and immune protection, and is associated with diarrhea, malabsorption and systemic invasion by microbial pathogens. A therapeutic diet and infection treatment may be unable to restore bifidobacteria and HMAGM. Besides refeeding and antibiotics, future trials including non-toxic missing microbes and nutrients necessary to restore bifidobacteria and HMAGM, including prebiotics and antioxidants, are warranted in children with severe or refractory disease. PMID- 26853756 TI - Impact of glenosphere size on clinical outcomes after reverse total shoulder arthroplasty: an analysis of 297 shoulders. AB - BACKGROUND: Although increasing glenosphere diameter has been found to increase passive range of motion (ROM) in simulated models of reverse total shoulder arthroplasty (rTSA), the clinical implications of glenosphere size are unclear. The purpose of our study was to determine the impact that glenosphere size had on short-term and midterm clinical outcomes, specifically American Shoulder and Elbow Surgeons (ASES) scores and ROM. METHODS: Prospectively collected data comparing patients receiving an rTSA with either a 38- or 42-mm glenosphere after a minimum 2-year follow-up were obtained. Clinical outcome measures included active ROM and ASES scores. RESULTS: We included 297 primary rTSAs in 290 patients: a 38-mm-diameter glenosphere was used in 160 shoulders and a 42-mm diameter glenosphere in 137 shoulders. Of the patients, 191 were women and 99 were men. The mean age at the time of surgery was 72 years (range, 50-88 years). At last follow-up, improvements in active forward elevation (aFE) and active external rotation (aER) were significantly greater in shoulders with a 42-mm glenosphere (+59 degrees vs +44 degrees for aFE and +24 degrees vs +18 degrees for aER). Female shoulders treated with a 42-mm glenosphere had significantly greater improvements in aFE, aER, and functional scores. Male shoulders treated with a 38-mm glenosphere had significantly greater improvements in pain levels and ASES scores but less improvement in aFE. Complications and rates of scapular notching were similar between glenosphere sizes. CONCLUSIONS: Patients treated with 42-mm glenospheres had greater improvements in aFE and aER when compared with 38-mm glenospheres. Our results suggest a potential association among gender, glenosphere size, and improvement in clinical outcome scores. LEVEL OF EVIDENCE: Level III; Retrospective Cohort Design; Treatment Study. PMID- 26853757 TI - Trends associated with distal biceps tendon repair in the United States, 2007 to 2011. AB - BACKGROUND: Current studies investigating surgical treatment of distal biceps tendon tears largely consist of small, retrospective case series. The purpose of this study was to investigate the current patient demographics, surgical trends, and postoperative complication rates associated with operative treatment of distal biceps tendon tears using a large database of privately insured, non Medicare patients. METHODS: Patients who underwent surgical intervention for distal biceps tendon tears from 2007 to 2011 were identified using the PearlDiver database. Demographic and surgical data as well as postoperative complications were reviewed. Statistical analysis was performed using linear regression analysis and chi(2) tests, with statistical significance set at P < .05. RESULTS: A total of 1443 patients underwent surgical treatment for distal biceps tendon tears. Men and patients aged 40 to 59 years accounted for 98% and 72% of the cohort, respectively. Regarding surgical technique, reinsertion to the radial tuberosity was preferred (95%) over tenodesis to the brachialis (5%) (P < .01). In total, revision surgery for tendon rerupture occurred in 5.4% of treated patients. The incidence of revision surgery for rerupture in acute and chronic distal biceps tears was 5.1% and 7.0%, respectively (P = .36). Postoperative infection and peripheral nerve injury rates were 1.1% and 0.6%, respectively. CONCLUSION: Surgeons strongly preferred anatomic reinsertion to the radial tuberosity for treatment, regardless of the chronicity of the injury. Postoperative complication rates were similar to those found in prior studies, although the true rate of rerupture may be higher than previously thought. PMID- 26853758 TI - Sports after shoulder arthroplasty: a comparative analysis of hemiarthroplasty and reverse total shoulder replacement. AB - BACKGROUND: Traditionally, fewer postoperative sport restrictions are imposed on hemiarthroplasty (HHA) patients on than reverse total shoulder arthroplasty (RTSA) patients. However, functional outcomes have been shown to be superior in RTSA. No direct comparison of RTSA vs HHA has been done on rates of return to sports in patients with glenohumeral arthritis and rotator cuff dysfunction, proximal humeral fractures, or rheumatoid arthritis. METHODS: This is a retrospective review of consecutive RTSA and HHA patients collected from our institution's shoulder arthroplasty registry. All patients playing sports preoperatively with minimum 1-year follow-up were included. Final follow-up included an additional patient-reported questionnaire with questions regarding physical fitness and sport activities. RESULTS: The study included 102 RTSA and 71 HHA patients. Average age at surgery was 72.3 years for RTSA compared with 65.6 years for HHA (P < .001). Patients undergoing RTSA had improved visual analog scale scores compared with HHA (-5.6 vs -4.2, P = .007), returned to sports after RTSA at a significantly higher rate (85.9% vs 66.7%, P = .02), and were more likely to be satisfied with their ability to play sports (P = .013). HHA patients were also more likely to have postoperative complaints than RTSA patients (63% vs 29%, P < .0001). No sports-related complications occurred. Female sex, age <70 years, surgery on the dominant extremity, and a preoperative diagnosis of arthritis with rotator cuff dysfunction predicted a higher likelihood of return to sports for patients undergoing RTSA compared with HHA. CONCLUSIONS: Despite traditional sport restrictions placed on RTSA, patients undergoing RTSA can return to sports at rates higher than those undergoing HHA, with fewer postoperative complaints. PMID- 26853759 TI - A systematic review and meta-analyses of sentinel lymph node identification in breast cancer and melanoma, a plea for tracer mapping. AB - PURPOSE: Sentinel lymph node biopsy (SLNB) has become a widely accepted staging procedure for both breast carcinoma and melanoma. The aim of our study was to systematically review different SLNB techniques and perform a meta-analysis for corresponding identification and false-negative rates. METHODS: A systematic review of the literature on SLNB in patients with early stage breast carcinoma and melanoma was performed. Only original study groups were included. The SLN identification rate and false negative rate were pooled for patients with breast carcinoma or melanoma according to radiocolloid tracer, blue dye, indocyanine green (ICG), or a combination of a radiocolloid tracer with blue dye or ICG. RESULTS: Between 1992 and 2012, a total of 154 studies (88 breast carcinoma and 66 melanoma) were reported that met our eligibility criteria. These studies included a total of 44,172 patients. The pooled SLN identification rate in breast carcinoma and melanoma patients using solely blue dye was 85% (range: 65-100%) and 84% (range: 59-100%), while for radiocolloid alone it was 94% (range: 67 100%) and 99% (range: 83-100%), respectively. Using a combination of radiocolloid and blue, identification rates were 95% (range 94-95%) and 98% (range: 98-98%). CONCLUSIONS: The current meta-analysis provides data that favors the use of radiocolloid or radiocolloid combined with a blue dye for SLN identification. Performing SLNB with radiocolloid alone is the technique of choice for experienced surgeons, since blue dye has multiple disadvantages. SLNB using ICG as a fluorescent dye seems a promising technique for the near future. PMID- 26853761 TI - Half-sandwich nickel complexes with ring-expanded NHC ligands - synthesis, structure and catalytic activity in Kumada-Tamao-Corriu coupling. AB - The general synthesis of [Ni(Cp)(X)(NHC)] complexes from a nickel halide, CpLi, and a carbene solution is reported. This procedure yields unprecedented complexes with ring-expanded NHC ligands (RE-NHC) of six- (1a, 1b), seven- (1c), and eight membered (1d) heterocycles. The NMR spectra of 1a-1d are consistent with the hindered rotation of Ni-Ccarbene and N-CMes bonds, while X-ray analyses of 1b, 1c, and 1d reveal a pronounced trans influence of the RE-NHC ligands. Complexes 1a-1e are efficient pre-catalysts in Kumada-Tamao-Corriu coupling with the maximum efficiency observed for complexes bearing the six-membered NHC. PMID- 26853760 TI - Prognosis after mastectomy versus repeat lumpectomy in patients with ipsilateral breast cancer recurrence: A propensity score analysis. AB - INTRODUCTION: Mastectomy is the current standard surgical procedure for ipsilateral breast tumor recurrence (IBTR). However, there is little evidence about the prognostic impact of the surgical procedure (mastectomy versus repeat lumpectomy) for IBTR. PATIENTS AND METHODS: A total of 271 consecutive patients who had histologically confirmed IBTR without distant metastases and underwent definitive surgery for IBTR between 1989 and 2008 were included from eight institutions in Japan. The impact of the surgical procedure for IBTR on distant disease-free survival (DDFS) and overall survival (OS) was evaluated using and multivariable proportional hazards regression and propensity score matching methods. RESULTS: Of the 271 patients, 149 patients (55%) underwent repeat lumpectomy and 122 patients (45%) underwent mastectomy after IBTR. The median follow-up period from definitive surgery for IBTR was 55 months. There was no difference in terms of DDFS and OS between repeat lumpectomy and mastectomy after IBTR, adjusted for various clinical and tumor characteristics. In addition, for the matched patient cohort, no difference in DDFS and OS was seen between the 2 groups. CONCLUSION: In our study, both multivariate analysis and the propensity score matching method demonstrated that there was no difference in terms of DDFS and OS between repeat lumpectomy and mastectomy after IBTR. Further studies are warranted (UMIN-CTR number UMIN000008136). PMID- 26853762 TI - Emigrated neuroscientists from Berlin to North America. AB - The highest number of German scholars and physicians, forced by the National Socialist regime to emigrate for "race" or political reasons, were from Berlin. Language and medical exams were requested differently in their new host country the United States-leading to a concentration of immigrants in the New York and Boston areas. Very early Emergency Committees in Aid of German Scholars and Physicians were established. Undergraduate students (like F. A. Freyhan, H. Lehmann, and H.-L. Teuber) from Berlin seemed to integrate easily, in contrast to colleagues of more advanced age. Some of the former chiefs and senior assistants of Berlin's neurological departments could achieve a successful resettlement (C. E. Benda, E. Haase, C. F. List, and F. Quadfasel) and some a minor degree of success (F. H. Lewy and K. Goldstein). A group of neuropsychiatrists from Bonhoeffer's staff at the Berlin Charite Hospital could rely on the forceful intercession of their former chief. The impact of the emigre colleagues on North American neuroscience is traced in some cases. Apart from the influential field of psychoanalysis, a more diffuse infiltration of German and European neuropsychiatry may be assumed. The contribution to the postwar blossoming of neuropsychology by the emigre neuroscientists K. Goldstein, F. Quadfasel, and H. L. Teuber is demonstrated in this article. PMID- 26853763 TI - Apelin-13 exerts antidepressant-like and recognition memory improving activities in stressed rats. AB - Apelin is the endogenous ligand for the G-protein-coupled receptor (APJ). The localization of APJ in limbic structures suggests a potential role for apelin in emotional processes. However, the role of apelin in the regulation of stress induced responses such as depression and memory impairment is largely unknown. In the present study, we evaluated the role of apelin-13 in the regulation of stress induced depression and memory impairment in rats. We report that repeated intracerebroventricular injections of apelin-13 reversed behavioral despair (immobility) in the forced swim (FS) test, a model widely used for the selection of new antidepressant agents. Apelin-13 also reversed behavioral deficits (escape failure) in the learned helplessness test. The magnitude of the antiimmobility and anti-escape failure effects of apelin-13 was comparable to that of imipramine, a classic antidepressant used as a positive control. Rats exposed to FS stress showed memory performance impairment in the novel object recognition test, and this impairment was improved by apelin-13 treatment. Apelin-13 did not affect recognition memory performance in non-stressed rats. Furthermore, the pretreatment of LY294002 (PI3K inhibitors) or PD98059 (ERK1/2 inhibitor) blocked apelin-13-mediated activities in FS-stressed rats. These findings suggest that apelin-13 exerts antidepressant-like and recognition memory improving activities through activating PI3K and ERK1/2 signaling pathways in stressed rats. PMID- 26853764 TI - CD44-specific nanoparticles for redox-triggered reactive oxygen species production and doxorubicin release. AB - CD44-specific and redox-responsive nanoparticles were prepared by coating a bioreducible chitosan-based nanoparticles with hyaluronic acid for intracellular glutathione-triggered reactive oxygen species (ROS) production and doxorubicin (DOX) release. Chitosan (CS) was conjugated with a copper chelator, D penicillamine (D-pen), to obtain a CS-SS-D-pen conjugate through the formation of a disulfide bond. D-pen release from the conjugate was triggered by intracellular glutathione (GSH) via reducing biologically reversible disulfide bonds. Self assembled CS-SS-D-pen nanoparticles were prepared through ionotropic gelation with tripolyphosphate and subsequently coated with hyaluronic acid (HA). The HA coated CS-SS-D-pen NPs were reduced by GSH to release free D-pen and trigger ROS production via a series of reactions involving Cu(II)-catalyzed D-pen oxidation and H2O2 generation. DOX was loaded into the HA-coated CS-SS-D-pen NPs by a method involving the complexation of DOX with Cu(II) ions. The Cu(II)-DOX complex loaded NPs exhibited redox-responsive release properties which accelerated DOX release at a higher glutathione level (10mM). Confocal fluorescence microscopy demonstrated that the Cu(II)-DOX-loaded NPs effectively delivered DOX to human colon adenocarcinoma cells (HT-29) by active targeting via HA-CD44 interactions. Intracellular ROS generated from the HA-coated CS-SS-D-pen NPs sensitized cancer cells to DOX-induced cytotoxicity. In vitro cytotoxicity assays revealed that Cu(II)-DOX-loaded NPs sensitized cells to DOX-induced cytotoxicity in CD44 overexpressing HT-29 cells compared to CD44 low-expressing HCT-15 cells. STATEMENT OF SIGNIFICANCE: In this manuscript, we develop a CD44-targetable loaded with nanoparticles Cu(II)-DOX complex. The nanoparticles exhibited redox responsive properties, which triggered reactive oxygen species (ROS) production and accelerated DOX release. The Cu(II)-DOX-loaded nanoparticle sensitized cells to DOX-induced cytotoxicity in CD44-overexpressing HT-29 cells. To our knowledge, this is the first report showing the combination of CD44-targeting and redox responsive property for triggering ROS production and subsequent drug release. We believe our findings would appeal to the readership of Acta Biomaterialia because the study bring new and interesting ideals in the development of specific and stimuli-responsive nanoparticles as drug carrier for cancer therapy. PMID- 26853766 TI - Highly luminescent nanoscale quasi-2D layered lead bromide perovskites with tunable emissions. AB - Herein, we report a new color tuning approach for highly luminescent nanoscale lead(ii) bromide perovskites with a quasi-2D layered structure. By synthetically manipulating the quasi-2D layered structure, different quantum size confinement effects can be realized to enable a precise color tuning of emissions ranging from deep blue to bright green. PMID- 26853765 TI - An anti-HER2 antibody conjugated with monomethyl auristatin E is highly effective in HER2-positive human gastric cancer. AB - Antibody-drug conjugate (ADC) is a novel class of therapeutics for cancer target therapy. This study assessed antitumor activity of ADC with an antimitotic agent, monomethyl auristatin E (MMAE) and a humanized monoclonal anti-HER2 antibody, hertuzumab, in gastric cancer. The efficacy of hertuzumab-MC-Val-Cit-PAB-MMAE (hertuzumab-vcMMAE) on human epidermal growth factor receptor 2 (HER2) positive human gastric cancer cells, NCI-N87, was evaluated in vitro and in vivo. The cytotoxicity of hertuzumab was significantly enhanced after conjugation with MMAE. Compared to trastuzumab, hertuzumab had a higher affinity to HER2 and had more potent antibody-dependent cell-mediated cytotoxicity (ADCC) activity in vitro. After conjugation with MMAE, the binding specificity for HER2 was not affected. Furthermore, the internalization of hertuzumab-vcMMAE in HER2 positive gastric cancer cells was verified. Although the conjugation of hertuzumab and MMAE decreased the ADCC effect, the overall cytotoxicity was dramatically increased in HER2 positive gastric cancer cells. In vitro data on this hertuzumab vcMMAE has exerted much stronger antitumor activity compared to trastuzumab-DM1 in HER2 positive gastric cancer cells. A single administration of hertuzumab vcMMAE at 5 or 10 mg/kg showed high potency and a sustained tumor inhibitory effect on NCI-N87 xenografts in mice. In conclusion, hertuzumab-vcMMAE conjugate is a highly effective anti-HER2 targeted therapy for HER2-positive gastric cancer. PMID- 26853767 TI - Preserved visual function with an orbital invasion of pituitary adenoma. AB - Pituitary adenomas rarely extend to the orbit through the optic foramen and superior orbital fissure. Compressive optic neuropathy could be caused by orbital invasion of the mass showing variable visual prognosis. We are reporting a patient with intact visual acuity after 3 years of a profound orbital invasion of pituitary adenoma. PMID- 26853768 TI - Ruthenium-Amine Conjugated Organometallic Materials for Multistate Near-IR Electrochromism and Information Storage. AB - Monometallic and dimetallic complexes with the ruthenium-amine conjugated structural unit have been prepared. These complexes display consecutive redox waves with low potentials and rich and intense absorptions in the near-infrared region. The electrochemical and spectroscopic properties can be modulated using substituents or auxiliary ligands with different electronic natures. Through simple functionalization, electropolymerized or monolayer thin films of these complexes have been prepared. These films display multistate near-infrared electrochromism with good contrast ratios and long optical retention times. In addition, flip-flop and flip-flap-flop memories have been demonstrated on the basis of these thin films. PMID- 26853770 TI - Pyrene-based heparin sensors in competitive aqueous media - the role of self assembled multivalency (SAMul). AB - Amine-functionalised pyrene derivatives are reported and their ability to detect heparin via a fluorescent response determined - different responses are observed dependent on whether self-assembled multivalent binding between sensor and analyte takes place, and ratiometric heparin sensors which can detect this surgically-relevant polyanion in competitive media are reported. PMID- 26853769 TI - A prospective study examining elder-relevant outcomes in older adults with prostate cancer undergoing treatment with chemotherapy or abiraterone. AB - BACKGROUND: Treatment of metastatic castration-resistant prostate cancer (mCRPC) with chemotherapy improves disease control and survival in fit older men (age 65+) but its impact on function is not clear. We hypothesized that chemotherapy would impair daily function in older men with mCRPC. METHODS: Men aged 65+ with mCRPC starting chemotherapy or abiraterone were enrolled in this prospective observational pilot study. Daily function was evaluated with the OARS Instrumental Activities of Daily Living (IADL) scale. Three objective measures were used to assess physical function. Patients completed Functional Assessment of Cancer Therapy questionnaires measuring prostate-specific and general quality of-life (QOL). Vulnerability was evaluated using the Vulnerable Elders Survey (VES-13). Assessments were completed before each cycle of chemotherapy or every 2 3 months for those receiving abiraterone. We compared outcomes pre- and post treatment and with published minimal clinically important differences. RESULTS: We evaluated 29 and 7 men on 1st-line and 2nd-line chemotherapy (median 6 and 7 cycles, respectively) and 11 men receiving abiraterone for a median 7 months. IADL scores declined slightly after 1st-line chemotherapy (mean -0.31 points, 95% confidence interval 0.39, -1.02). Physical performance remained stable over time. Both general and prostate-specific QOL improved with 1st-line chemotherapy. For all but one outcome (Timed Chair Stands), vulnerable men had similar changes over time compared to non-vulnerable men. Second-line chemotherapy and abiraterone were generally well-tolerated. CONCLUSION: IADL function declined slightly whereas physical function remained stable and QOL improved during chemotherapy. Vulnerable and non-vulnerable older men with mCRPC appear to tolerate 1st-line chemotherapy fairly well. PMID- 26853771 TI - The efficacy of hemodialysis in interventional therapy in coronary artery disease patients with chronic renal insufficiency. AB - The aim of this study was to explore the efficacy and safety of hemodialysis in interventional therapy for patients with coronary artery disease combined with chronic renal insufficiency. With the aging and social development, the number of coronary artery disease patients with chronic renal insufficiency gradually increased. Total 58 coronary heart disease patients with chronic renal dysfunction were selected. These patients were characterized with typical angina symptoms and typical electrocardiogram (ECG) changes of onset angina. Continuous oral administration of sodium bicarbonate tablets 1 g 3/day * 3 days and slow intravenous input sodium chloride 1000 ~1500 mL 3-12 h before operation were given. By this way, all patients were treated by hydration and alkalization. After percutaneous coronary intervention (PCI) treatment, patients were immediately transferred to undergo 4 h of dialysis treatment without removing indwelling of femoral artery puncture sheath tube to protect renal function. Changes in renal function including serum creatinine, glomerular filtration rate, and urine were observed and recorded. All patients were successfully underwent PCI treatment. Within one month after PCI, there were no obvious complication and no stent thrombosis occurred. Among of 58 patients, 56 cases showed no significant increase in serum creatinine levels compared with those before operation. However, serum creatinine level of one patient increased to 251 umol/L and one patient still required permanent dialysis. Using hemodialysis in interventional therapy in coronary artery disease patients with chronic renal insufficiency could significantly improve the prognosis of the patients. PMID- 26853772 TI - Structural determination of niobium-doped silicon clusters by far-infrared spectroscopy and theory. AB - In this work, the structures of cationic SinNb(+) (n = 4-12) clusters are determined using the combination of infrared multiple photon dissociation (IR MPD) and density functional theory (DFT) calculations. The experimental IR-MPD spectra of the argon complexes of SinNb(+) are assigned by comparison to the calculated IR spectra of low-energy structures of SinNb(+) that are identified using the stochastic 'random kick' algorithm in conjunction with the BP86 GGA functional. It is found that the Nb dopant tends to bind in an apex position of the Sin framework for n = 4-9 and in surface positions with high coordination numbers for n = 10-12. For the larger doped clusters, it is suggested that multiple isomers coexist and contribute to the experimental spectra. The structural evolution of SinNb(+) clusters is similar to V-doped silicon clusters (J. Am. Chem. Soc., 2010, 132, 15589-15602), except for the largest size investigated (n = 12), since V takes an endohedral position in Si12V(+). The interaction with a Nb atom, with its partially unfilled 4d orbitals leads to a significant stability enhancement of the Sin framework as reflected, e.g. by high binding energies and large HOMO-LUMO gaps. PMID- 26853774 TI - Entanglements in polymer nanocomposites containing spherical nanoparticles. AB - We investigate the polymer packing around nanoparticles and polymer/nanoparticle topological constraints (entanglements) in nanocomposites containing spherical nanoparticles in comparison to pure polymer melts using molecular dynamics (MD) simulations. The polymer-nanoparticle attraction leads to good dispersion of nanoparticles. We observe an increase in the number of topological constraints (decrease of total entanglement length Ne with nanoparticle loading in the polymer matrix) in nanocomposites due to nanoparticles, as evidenced by larger contour lengths of the primitive paths. An increase of the nanoparticle radius reduces the polymer-particle entanglements. These studies demonstrate that the interaction between polymers and nanoparticles does not affect the total entanglement length because in nanocomposites with small nanoparticles, the polymer-nanoparticles topological constraints dominate. PMID- 26853776 TI - Correction to Lancet Oncol 2016; 17: 65. PMID- 26853773 TI - Development of a high-resolution melting marker for selecting Fusarium crown and root rot resistance in tomato. AB - Fusarium crown and root rot is a severe fungal disease of tomato caused by Fusarium oxysporum f. sp. radicis-lycopersici (FORL). In this study, the genomic location of the FORL-resistance locus was determined using a set of molecular markers on chromosome 9 and an F2 population derived from FORL-resistant inbred 'AV107-4' (Solanum lycopersicum) * susceptible 'L3708' (Solanum pimpinellifolium). Bioassay performed using Korean FORL strain KACC 40031 showed single dominant inheritance of FORL resistance in the F2 population. In all, 13 polymerase chain reaction-based markers encompassing approximately 3.6-72.0 Mb of chromosome 9 were developed based on the Tomato-EXPEN 2000 map and SolCAP Tomato single nucleotide polymorphism array analysis. These markers were genotyped on 345 F2 plants, and the FORL-resistance locus was found to be present on a pericentromeric region of suppressed chromosomal recombination in chromosome 9. The location of the FORL-resistance locus was further confirmed by testing these markers against diverse commercial tomato and stock cultivars resistant to FORL. A restriction fragment length polymorphism marker, PNU-D4, located at approximately 6.1 Mb of chromosome 9 showed the highest match with the resistance locus and was used for conducting high-resolution melting analysis for marker assisted selection of FORL resistance. PMID- 26853777 TI - Correction to Lancet Oncol 2015; 16: 303. PMID- 26853778 TI - Correction to Lancet Oncol 2016; 17: e8. PMID- 26853784 TI - Photoelectron transport tuning of self-assembled subbands. AB - Conventionally, electrical transport of quantum subbands occurs at very high electric fields, indicating that the medium is easy to break down. In the experiments and practical applications, the extreme condition is difficult to satisfy. For quantum information transmission, low power consumption and convenient implementation are what we expect. In this paper, we engineered a special quantum dot array (QDA) embedded in a single crystal matrix. By external optical field excitation, we found a series of subbands made of the self assembled QDA discretely located in the matrix. Changing the spacing between the quantum dots leads to the variation of subband spacing. Artificially manipulating the microcosmic QDA system can bring interesting macroscopic effects, such as an enhanced absorption intensity in the ultraviolet range, a blue-shift of the surface plasmon resonance peak and nonlinear absorption changed from two-photon absorption to saturated absorption. The intrinsic mechanism of the subband optical response was revealed due to the strong quantum confinement effect and dominant intraband transitions. The weak surface plasmon resonance absorption of Ni QDA gave an excellent figure of merit of the order of 10(-10). The composite films are expectation enough to become a prime candidate for nonlinear applications near 532 nm. Therefore with interplay of the weak optical field and subbands, we achieved a tunable photoelectron transport process. PMID- 26853779 TI - Identification and molecular characterization of oat peptides implicated on coeliac immune response. AB - BACKGROUND: Oats provide important nutritional and pharmacological properties, although their safety in coeliac patients remains controversial. Previous studies have confirmed that the reactivity of the anti-33-mer monoclonal antibody with different oat varieties is proportional to the immune responses in terms of T cell proliferation. Although the impact of these varieties on the adaptive response has been studied, the role of the dendritic cells (DC) is still poorly understood. The aim of this study is to characterize different oat fractions and to study their effect on DC from coeliac patients. METHODS AND RESULTS: Protein fractions were isolated from oat grains and analyzed by SDS-PAGE. Several proteins were characterized in the prolamin fraction using immunological and proteomic tools, and by Nano-LC-MS/MS. These proteins, analogous to alpha- and gamma-gliadin-like, showed reactive sequences to anti-33-mer antibody suggesting their immunogenic potential. That was further confirmed as some of the newly identified oat peptides had a differential stimulatory capacity on circulating DC from coeliac patients compared with healthy controls. CONCLUSIONS: This is the first time, to our knowledge, where newly identified oat peptides have been shown to elicit a differential stimulatory capacity on circulating DC obtained from coeliac patients, potentially identifying immunogenic properties of these oat peptides. PMID- 26853786 TI - An improved method for isolation of epithelial and stromal cells from the human endometrium. AB - We aimed to improve the efficiency of isolating endometrial epithelial and stromal cells (EMECs and EMSCs) from the human endometrium. We revealed by immunohistochemical staining that the large tissue fragments remaining after collagenase treatment, which are usually discarded after the first filtration in the conventional protocol, consisted of glandular epithelial and stromal cells. Therefore, we established protease treatment and cell suspension conditions to dissociate single cells from the tissue fragments and isolated epithelial (EPCAM positive) and stromal (CD13-positive) cells by fluorescence-activated cell sorting. Four independent experiments showed that, on average, 1.2 * 10(6) of EMECs and 2.8 * 10(6) EMSCs were isolated from one hysterectomy specimen. We confirmed that the isolated cells presented transcriptomic features highly similar to those of epithelial and stromal cells obtained by the conventional method. Our improved protocol facilitates future studies to better understand the molecular mechanisms underlying the dynamic changes of the endometrium during the menstrual cycle. PMID- 26853785 TI - The efficiency of vaginal temperature measurement for detection of estrus in Japanese Black cows. AB - Recently, weak estrous behavior was assumed to be the cause of a decline in breeding efficiency in cattle. The present study investigated the effect of measuring the vaginal temperature on the detection of estrus in Japanese Black cows. First, the effect of hormone administration to cows with a functional corpus luteum on the vaginal temperature was evaluated by continuous measurement using a temperature data logger. After 24 h of cloprostenol (PG) treatment, the vaginal temperature was significantly lower than on day 7 after estrus, and the low values were maintained until the beginning of estrus (P < 0.05). The cows that received PG and exogenous progesterone (CIDR) did not show a temperature decrease until the CIDR was removed. This finding suggested that the vaginal temperature change reflected the progesterone concentration. The rate of detection of natural estrus was lower for a pedometer than for the vaginal temperature (P < 0.05); synchronization of estrus resulted in a high estrus detection rate regardless of the detection method. In a subsequent experiment, the effect of vaginal temperature measurement and the use of a pedometer on estrus detection was evaluated in the cool and hot seasons. The average activities during non-estrus and the activity increase ratio (estrus/non-estrus) changed according to season (P < 0.01, P < 0.05). However, the average vaginal temperatures during estrus and non-estrus were not affected by season. The estrus detection rate of the pedometer was lower in summer and lower than that obtained using the vaginal temperature. These results indicated that vaginal temperature measurement might be effective for detecting estrus regardless of estrous behavior. PMID- 26853787 TI - Positive correlations of age and parity with plasma concentration of macrophage migration inhibitory factor in Japanese black cows. AB - Plasma Macrophage migration inhibitory factor (MIF) concentration correlates positively with age, and negatively with self-rated health in women, and optimal MIF concentration may promote proper reproductive function. This study was conducted to evaluate the hypotheses that plasma MIF concentration changes with parturition or postpartum first ovulation, and that age in months and parity correlate with plasma MIF concentration in Japanese black cows. Western blotting utilizing an anti-MIF mouse monoclonal antibody of various tissues and plasma from females indicated that MIF expression was stronger in the anterior pituitary than in other tissues. We developed a competitive EIA utilizing the same anti-MIF mouse monoclonal antibody with sufficient sensitivity and reliable performance for measuring bovine plasma samples. We then measured MIF concentrations in bovine plasma collected from 4 weeks before parturition to 4 weeks after postpartum first ovulation. There was no significant difference in plasma MIF concentration pre- and post-parturition, or before and after the postpartum first ovulation. Plasma MIF concentrations were positively correlated (P < 0.01) with parity (r = 0.703), age in months on the day of parturition (r = 0.647), and age in months on the day of the postpartum first ovulation (r = 0.553) when we used almost all data, except for that from a third-parity cow with an abnormally high plasma MIF concentration. We therefore concluded that plasma MIF concentrations may increase with age in months and parity, but do not change either before and after parturition or before and after postpartum first ovulation in Japanese black cows. PMID- 26853788 TI - Transcription of follicle-stimulating hormone subunit genes is modulated by porcine LIM homeobox transcription factors, LHX2 and LHX3. AB - The LIM-homeobox transcription factors LHX2 and LHX3s (LHX3a and LHX3b) are thought to be involved in regulating the pituitary glycoprotein hormone subunit genes Cga and Fshbeta. These two factors show considerable differences in their amino acid sequences for DNA binding and protein-protein interactions and in their vital function in pituitary development. Hence, we compared the DNA binding properties and transcriptional activities of Cga and Fshbeta between LHX2 and LHX3s. A gel mobility shift assay for approximately 1.1 kb upstream of Cga and 2.0 kb upstream of Fshbeta varied in binding profiles between LHX2 and LHX3s. DNase I footprinting revealed DNA binding sites in 8 regions of the Cga promoter for LHX2 and LHX3s with small differences in the binding range and strength. In the Fshbeta promoter, 14 binding sites were identified for LHX2 and LHX3, respectively. There were alternative binding sites to either gene in addition to similar differences observed in the Cga promoter. The transcriptional activities of LHX2 and LHX3s according to a reporter assay showed cell-type dependent activity with repression in the pituitary gonadotrope lineage LbetaT2 cells and stimulation in Chinese hamster ovary lineage CHO cells. Reactivity of LHX2 and LHX3s was observed in all regions, and differences were observed in the 5' upstream region of Fshbeta. However, immunohistochemistry showed that LHX2 resides in a small number of gonadotropes in contrast to LHX3. Thus, LHX3 mainly controls Cga and Fshbeta expression. PMID- 26853789 TI - Assessment of the endoscopic retrograde cholangiopancreatography grading system: A prospective study from a tertiary care center. AB - BACKGROUND/AIMS: The American Society for Gastrointestinal Endoscopy (ASGE) endoscopic retrograde cholangiopancreatography (ERCP) grading system was proposed but has not been fully evaluated with prospective clinical studies. In this study, we aimed to evaluate the effectiveness of the ERCP difficulty grading system for predicting success and adverse event rates related to the procedure. MATERIALS AND METHODS: A total of 1057 ERCP procedures performed on 752 patients were included in the present study. The complexity grades of the procedures were recorded according to the ASGE grading system. Specific complications of ERCP (pancreatitis, cholangitis, bleeding, and perforation) were also defined and graded. RESULTS: The procedure difficulty was determined as 1st degree in 153 patients (14.4%), 2nd degree in 498 patients (47.1%), 3rd degree in 271 (25.6%), and 4th degree in 135 patients (12.7%). The success rate for the entire procedures was 88.4%. The success rate for 1st degree procedures was 99.3%, 97.2% for 2nd degree procedures, 86.7% for 3rd degree procedures, and 46.7% for 4th degree procedures (p<0.005). When the difficulty of the procedures increased from 1 to 4, the adverse event rates increased from 1.3% to 10.4%. CONCLUSION: The findings support the evidence that the difficulty degrees of ERCP procedures can help predict the success and complication rates of the procedure. Because of the increased rates of failure and complications in more difficult cases, the procedures should be performed by experienced endoscopists in advanced centers. PMID- 26853790 TI - The predictive value of noninvasive serum markers of liver fibrosis in patients with chronic hepatitis C. AB - BACKGROUND/AIMS: This study aims to show the predictive value of noninvasive serum markers on the hepatic fibrosis level. MATERIALS AND METHODS: This cross sectional study involves 120 patients with chronic hepatitis C. The noninvasive markers used were as follows: age-platelet index (AP index), cirrhosis discriminant score (CDS), aspartate aminotransferase (AST)-alanine aminotransferase (ALT) ratio (AAR), fibrosis-4 (FIB-4) index, AST-platelet ratio index (APRI), Goteborg University Cirrhosis Index (GUCI), FibroQ, King's score, platelet count. Concurrent liver biopsies were evaluated using the modified Ishak and Knodell scoring systems. In accordance with the Knodell scores, F3-F4 scores were defined as "severe fibrosis," and the modified Ishak scores stage of >=3 (F3 F6) were defined as "clinically significant fibrosis." Receiver Operating Characteristic (ROC) curve analyses were carried out to compare the noninvasive markers with hepatic fibrosis level. RESULTS: Mean age of the patients was 51.7+/ 11.6. A total of 10 patients (8.3%) with Knodell scores and 24 patients (20%) with modified Ishak scores were evaluated to have >=F3 hepatic fibrosis. ROC analyses with the Knodell and modified Ishak scores were as follows: AP index=0.61-0.57, CDS=0.66-0.55, AAR=0.60-0.49, FIB-4=0.70-0.68, APRI=0.67-0.72, GUCI=0.66-0.72, FibroQ=0.64-0.54, King's score=0.68-0.54, platelet count=0.61 0.55. CONCLUSION: We found that APRI, FIB-4, King's score, and GUCI can be used to determination patients with mild fibrosis with a high negative predictive value and in the differentiation of severe/significant fibrosis from mild to moderate fibrosis. PMID- 26853791 TI - Helicobacter pylori and metabolic syndrome. PMID- 26853792 TI - Study of ideal topical pharyngeal anesthesia in upper gastrointestinal system endoscopy: A double-blind, randomized, controlled trial. AB - BACKGROUND/AIMS: This study is designed to determine which drug forms provide ideal pharyngeal anesthesia when used during upper gastrointestinal system endoscopy. MATERIALS AND METHODS: A total of 180 patients were included in the study. Using the random number table, these patients were divided into three groups. Group 1, lidocaine gel+isotonic spray; Group 2, base lubricant gel+lidocaine spray; and Group 3: lidocaine gel+lidocaine spray. Data were collected from the patient identification form, compliance to operation form, and State Anxiety Inventory. RESULTS: Anesthetization and compliance to procedure scores were higher and anxiety scores were lower in Group 3 than in other groups (p<0.05). It was observed that as the compliance score increased, the anesthetization and satisfaction scores also increased; however, coughing during the procedure, duration of the procedure, and anxiety scores decreased (p<0.05). It was determined that as anesthetization scores increased, discomfort in the throat caused by the device, coughing during the procedure, and anxiety scores decreased (p<0.05). CONCLUSION: Lidocaine gel and spray combination is the most ideal pharyngeal anesthesia to ensure the adaptation of the patient to the procedure and to decrease anxiety and discomfort during the procedure. PMID- 26853794 TI - Prevalence of QT interval prolongation in inflammatory bowel disease. AB - BACKGROUND/AIMS: There is growing evidence linking various cardiac complications with inflammatory bowel disease (IBD). Electrolyte abnormalities, chronic inflammation, and medication use (such as Infliximab) that are associated with IBD are all independent risk factors for QT interval prolongation. Given that malignant ventricular arrhythmias are associated with QT interval prolongation, it is important to risk stratify this subset of patients. Our objective was to evaluate the prevalence of abnormal QT interval prolongation (defined by a QT interval of >450 ms in men and >460 ms in women) in an IBD population. MATERIALS AND METHODS: A retrospective chart review of patients with IBD from the Metro Hospital database was performed. Patients' demographic characteristics and laboratory data were abstracted. "RR" and "QT" intervals were measured from the last available electrocardiogram, and corrected QT (QTc) interval was calculated from lead II using Bazett's formula. RESULTS: Of 142 eligible patients, 42.3% (n=22/52) of males and 48.9% (n=44/90) of females had a prolonged QTc interval. Patients with IBD having a prolonged QTc interval had a higher body mass index than those with a normal QTc interval (29.7+/-6.9 vs. 26.2+/-5.9, p=0.005). CONCLUSION: Our study demonstrates that patients with IBD are at a higher risk of developing QTc interval prolongation. PMID- 26853793 TI - Evaluation of endoscopic findings for discriminating between early carcinomas and low-grade adenomas in superficial elevated gastric lesions. AB - BACKGROUND/AIMS: This study aimed to determine the useful endoscopic findings in a differential diagnosis between early carcinomas (EC) and low-grade adenomas (LGA) in superficial elevated gastric epithelial neoplasia during conventional endoscopy with white-light imaging (C-WLI). MATERIALS AND METHODS: We investigated 270 consecutive cases of superficial elevated gastric epithelial neoplasias, which were removed by endoscopic submucosal dissection. The pathological diagnostic criteria were based on the revised Vienna classification: category 4 (mucosal high-grade neoplasia) or 5 (submucosal invasion by carcinoma) lesions were diagnosed as EC, while category 3 (mucosal low-grade neoplasia) lesions were diagnosed as LGA. The association between the postoperative pathological diagnoses (EC or LGA) and the following endoscopic findings: localized site, lesion size, color (reddish or whitish), shape (smooth, petal, or irregular), and presences of depression, erosion, ulceration, or nodularity on the surface, were evaluated. RESULTS: Of 270 epithelial neoplasias, 222 (58 LGA and 164 EC) were retrospectively evaluated. Multiple logistic regression analysis revealed that the lesion size [odds ratio (OR), 1.216; p<0.001) and reddish color (OR, 5.274; p<0.001) were independent findings for EC. CONCLUSION: The lesion size and reddish color were useful optical findings for discriminating between EC and LGA. PMID- 26853795 TI - Nitric Oxide as a Marker for Levo-Thyroxine Therapy in Subclinical Hypothyroid Patients. AB - Subclinical hypothyroidism (SH) is characterized by a mildly elevated concentration of thyroid stimulating hormone (TSH) despite free thyroxine (FT4) and triiodothyronine (FT3) levels within the reference range. Numerous studies revealed SH to be an independent risk factor for cardiovascular disease (CVD), including atherosclerosis, congestive heart failure, coronary heart disease, ischemic heart disease and the associated mortality. The relationship between SH and CVD is well documented, but the molecular mechanism underlying this correlation remain unknown. Endothelial dysfunction has been recognized as an initial step leading to CVD in patients with SH. Changes in lipid profile, inflammation and/or oxidative stress contribute to the endothelial dysfunction in SH. Moreover, the progression of SH is characterized by significantly decreased nitrite and nitrate levels. Recent animal and clinical studies discussed in this review suggest that nitric oxide (NO) levels could be a reliable biomarker for cardiovascular risk in SH. Understanding the regulation of NO production by thyroid hormone may provide novel and useful knowledge regarding how endothelial dysfunction in SH is linked with CVD and help us to uncover new treatments for SH. We suggest that serum NO level may be an indicator for the introduction and dosage of levothyroxine (LT4) replacement therapy in SH patients. Future studies should focus on understanding the molecular mechanisms underlying the effects of NO in physiological as well as in pathophysiological conditions such as hypothyroidism and their clinical relevance. PMID- 26853796 TI - The role of non-rapid eye movement slow-wave activity in prefrontal metabolism across young and middle-aged adults. AB - Electroencephalographic slow-wave activity (0.5-4 Hz) during non-rapid eye movement (NREM) sleep is a marker for cortical reorganization, particularly within the prefrontal cortex. Greater slow wave activity during sleep may promote greater waking prefrontal metabolic rate and, in turn, executive function. However, this process may be affected by age. Here we examined whether greater NREM slow wave activity was associated with higher prefrontal metabolism during wakefulness and whether this relationship interacted with age. Fifty-two participants aged 25-61 years were enrolled into studies that included polysomnography and a (18) [F]-fluoro-deoxy-glucose positron emission tomography scan during wakefulness. Absolute and relative measures of NREM slow wave activity were assessed. Semiquantitative and relative measures of cerebral metabolism were collected to assess whole brain and regional metabolism, focusing on two regions of interest: the dorsolateral prefrontal cortex and the orbitofrontal cortex. Greater relative slow wave activity was associated with greater dorsolateral prefrontal metabolism. Age and slow wave activity interacted significantly in predicting semiquantitative whole brain metabolism and outside regions of interest in the posterior cingulate, middle temporal gyrus and the medial frontal gyrus, such that greater slow-wave activity was associated with lower metabolism in the younger participants and greater metabolism in the older participants. These results suggest that slow-wave activity is associated with cerebral metabolism during wakefulness across the adult lifespan within regions important for executive function. PMID- 26853798 TI - The effectiveness of a dentifrice without sodium lauryl sulphate on dental plaque and gingivitis - a randomized controlled clinical trial. AB - OBJECTIVES: The purpose of the study was to evaluate the effect on dental plaque and gingivitis of a dentifrice without sodium lauryl sulphate (SLS) compared to two SLS-containing dentifrices. MATERIAL AND METHODS: For this double-blind, parallel study, 90 volunteers having moderate gingival inflammation (>=40%) were randomly divided among three groups: one group using non-SLS dentifrice containing enzymes, colostrum and low concentrations of zinc and two control groups each using different SLS-containing dentifrices. Dental plaque scores (Turesky modification of Quigley & Hein) and gingivitis scores (Bleeding On Marginal Probing) were assessed at baseline, after 2 and 4 weeks. RESULTS: Eighty nine participants provided evaluable data. A slight decrease in gingivitis scores was observed for all groups over 4 weeks, which was statistically significant for the non-SLS group. Mean values for dental plaque scores did not show major differences over 4 weeks. For both parameters, no significant differences between groups could be observed at any time point. Patient appreciation was in favour of the SLS groups especially regarding the foaming effect. CONCLUSION: No significant differences could be observed with respect to the effect on plaque and gingivitis between SLS-containing and SLS-free dentifrice containing enzymes, colostrum and low concentration zinc. Patients enjoyed the duration of taste and the 'foaming effect' of SLS-containing dentifrices better. PMID- 26853799 TI - Comparative anatomy of the extraocular muscles in four Myliobatoidei rays (Batoidea, Myliobatiformes). AB - Extraocular muscles are classically grouped as four rectus and two oblique muscles. However, their description and potential associations with species behavior are limited. The objective was to characterize extraocular muscles in four Myliobatoidei rays from diverse habitats with divergent behaviors. Heads (10 per species) of Dasyatis hypostigma, Gymnura altavela, Mobula thurstoni and Pteroplatytrygon violacea were decalcified and dissected to characterize and describe extraocular muscles. Principal component analysis (PCA) was used to evaluate relationships between muscle length and species; for P. violacea, D. hypostigma and G. altavela, these were qualitatively and quantitatively consistent with the general pattern of extraocular muscles in vertebrates. In contrast, for M. thurstoni, the two oblique muscles were completely fused and there was a seventh extraocular muscle, named m. lateral rectus beta (both were apparently novel findings in this species). There were also significant differences in eye disposition in the chondrocranium. The PCA axis 1 (rectus muscles) and PCA axis 2 (oblique muscles) accounted for 98.47% of data variability. Extraocular muscles had significant differences in length and important anatomical differences among sampled species that facilitated grouping species according to their life history. In conclusion, extraocular muscles are not uniform in all vertebrate species, thereby providing another basis for comparative studies. PMID- 26853797 TI - Novel small RNA (sRNA) landscape of the starvation-stress response transcriptome of Salmonella enterica serovar typhimurium. AB - Small RNAs (sRNAs) are short (~50-200 nucleotides) noncoding RNAs that regulate cellular activities across bacteria. Salmonella enterica starved of a carbon energy (C) source experience a host of genetic and physiological changes broadly referred to as the starvation-stress response (SSR). In an attempt to identify novel sRNAs contributing to SSR control, we grew log-phase, 5-h C-starved and 24 h C-starved cultures of the virulent Salmonella enterica subspecies enterica serovar Typhimurium strain SL1344 and comprehensively sequenced their small RNA transcriptomes. Strikingly, after employing a novel strategy for sRNA discovery based on identifying dynamic transcripts arising from "gene-empty" regions, we identify 58 wholly undescribed Salmonella sRNA genes potentially regulating SSR averaging an ~1,000-fold change in expression between log-phase and C-starved cells. Importantly, the expressions of individual sRNA loci were confirmed by both comprehensive transcriptome analyses and northern blotting of select candidates. Of note, we find 43 candidate sRNAs share significant sequence identity to characterized sRNAs in other bacteria, and ~70% of our sRNAs likely assume characteristic sRNA structural conformations. In addition, we find 53 of our 58 candidate sRNAs either overlap neighboring mRNA loci or share significant sequence complementarity to mRNAs transcribed elsewhere in the SL1344 genome strongly suggesting they regulate the expression of transcripts via antisense base-pairing. Finally, in addition to this work resulting in the identification of 58 entirely novel Salmonella enterica genes likely participating in the SSR, we also find evidence suggesting that sRNAs are significantly more prevalent than currently appreciated and that Salmonella sRNAs may actually number in the thousands. PMID- 26853800 TI - Neurodevelopmental long-term outcome in children with hydrocephalus requiring neonatal surgical treatment. AB - PURPOSE: To assess long-term neurodevelopmental outcome in children with hydrocephalus requiring neurosurgical treatment during the neonatal period. METHODS: This prospective longitudinal population-based study included 43 children with neonatal shunted hydrocephalus. The 43 children were prospectively reviewed in the presence of their parents at the outpatient clinic. Cognitive and motor outcomes were assessed respectively using different Wechsler scales according to age and Gross Motor Function Classification System (GMFCS). Postoperative MRI was routinely performed. RESULTS: The mean gestational age at birth of the 43 consecutive children with neonatal hydrocephalus (sex ratio M/F: 1.39) was 34.5+/-5.4 weeks of gestation. At mean follow-up of 10.4+/-4 years, mean total IQ was 73+/-27.7, with equivalent results in mean verbal and mean performance IQ. Of the 33 children with IQ evaluation, 18 presented an IQ>=85 (41.9%). Efficiency in walking without a mobility device (GMFCS<=2) was obtained in 37 children (86%). Only severity of postoperative ventricular dilation was significantly associated with unfavorable outcome (Evans index>0.37; odds ratio: 0.16, P=0.03). CONCLUSION: This information could be provided to those families concerned who often experience anxiety when multi-disciplinary management of neonatal hydrocephalus is required. PMID- 26853802 TI - The Impact of Exogenous Factors on Respiratory Pathogen-Induced Innate Alveolar Macrophage Responses in COPD. AB - Alveolar macrophages in chronic obstructive pulmonary disease (COPD) have fundamentally impaired innate immune responses to toll-like receptor (TLR) ligands of nontypeable Haemophilus influenzae (NTHI). However, whether dysfunctional inflammatory responses in COPD extend to macrophage interactions with intact respiratory pathogens beyond NTHI has not been explored. Furthermore, the influences of exogenous factors, including active smoking and medications, on pathogen-induced innate immune responses have only begun to be investigated. We hypothesized that distinct alveolar macrophage impairments in COPD are not limited to NTHI TLR ligands and that active smoking and select COPD medications modulate innate responses. Alveolar macrophages, obtained from COPD ex-smokers (n = 32) and active smokers (n = 64) by bronchoalveolar lavage (BAL), were incubated with NTHI, Moraxella catarrhalis, and Streptococcus pneumoniae, and with TLR2 and TLR4 ligands. Elicited IL-8 and TNF-alpha were measured by multianalyte microsphere flow cytometry to determine proinflammatory responsiveness. Induced IL-8, but not TNF-alpha, was greater from alveolar macrophages of active smokers compared with ex-smokers, in response to NTHI (p = 0.04), M. catarrhalis (p = 0.003), and S. pneumoniae (p = 0.03). Both IL-8 and TNF-alpha induction by TLR2 and TLR4 ligands were greater in active smokers. While intergroup NTHI- and M. catarrhalis-induced TNF-alpha levels were no different, they were notably lower among ex-smokers taking anticholinergic medications (p < 0.04 for each), but not with any other bronchoactive medications. Our results support a paradigm of distinct immunologic responses of COPD alveolar macrophages of ex- and active smokers to diverse respiratory pathogens and highlight a subset of ex-smokers whose diminished alveolar macrophage responsiveness may be associated with anticholinergic agents. PMID- 26853801 TI - Common electronic origin of superconductivity in (Li,Fe)OHFeSe bulk superconductor and single-layer FeSe/SrTiO3 films. AB - The mechanism of high-temperature superconductivity in the iron-based superconductors remains an outstanding issue in condensed matter physics. The electronic structure plays an essential role in dictating superconductivity. Recent revelation of distinct electronic structure and high-temperature superconductivity in the single-layer FeSe/SrTiO3 films provides key information on the role of Fermi surface topology and interface in inducing or enhancing superconductivity. Here we report high-resolution angle-resolved photoemission measurements on the electronic structure and superconducting gap of an FeSe-based superconductor, (Li0.84Fe0.16)OHFe0.98Se, with a Tc at 41 K. We find that this single-phase bulk superconductor shows remarkably similar electronic behaviours to that of the superconducting single-layer FeSe/SrTiO3 films in terms of Fermi surface topology, band structure and the gap symmetry. These observations provide new insights in understanding high-temperature superconductivity in the single layer FeSe/SrTiO3 films and the mechanism of superconductivity in the bulk iron based superconductors. PMID- 26853803 TI - Tissue Engineered Airways: A Prospects Article. AB - An ideal tracheal scaffold must withstand luminal collapse yet be flexible, have a sufficient degree of porosity to permit vascular and cellular ingrowth, but also be airtight and must facilitate growth of functional airway epithelium to avoid infection and aid in mucocilliary clearance. Finally, the scaffold must also be biocompatible to avoid implant rejection. Over the last 40 years, efforts to design and manufacture the airway have been undertaken worldwide but success has been limited and far apart. As a result, tracheal resection with primary repair remains the Gold Standard of care for patients presenting with airway disorders and malignancies. However, the maximum resectable length of the trachea is restricted to 30% of the total length in children or 50% in adults. Attempts to provide autologous grafts for human application have also been disappointing for a host of different reasons, including lack of implant integration, insufficient donor organs, and poor mechanical strength resulting in an unmet clinical need. The two main approaches researchers have taken to address this issue have been the development of synthetic scaffolds and the use of decellularized organs. To date, a number of different decellularization techniques and a variety of materials, including polyglycolic acid (PGA) and nanocomposite polymers have been explored. The findings thus far have shown great promise, however, there remain a significant number of caveats accompanying each approach. That being said, the possibilities presented by these two approaches could be combined to produce a highly successful, clinically viable hybrid scaffold. This article aims to highlight advances in airway tissue engineering and provide an overview of areas to explore and utilize in accomplishing the aim of developing an ideal tracheal prosthesis. J. Cell. Biochem. 117: 1497-1505, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26853804 TI - Decreased levels of aquaporin-4 in the cerebrospinal fluid of patients with idiopathic intracranial hypertension. AB - BACKGROUND: Idiopathic intracranial hypertension is characterized by increased intracranial pressure. Its pathogenesis is largely unknown. Aquaporins may play a role in the homeostasis of cerebrospinal fluid. METHODS: We aimed to elucidate the role of aquaporins in idiopathic intracranial hypertension by measuring the level of aquaporin-1 and aquaporin-4 in the cerebrospinal fluid and plasma of 28 patients and 29 controls by enzyme-linked immunosorbent assay. The adipokines leptin and retinol-binding protein 4 were also measured. RESULTS: We found a reduction in aquaporin-4 in the cerebrospinal fluid of patients. Leptin levels were increased in the cerebrospinal fluid and plasma of patients and were correlated with weight, body mass index and body fat. There was no difference between patients and controls in the levels of aquaporin-1 and retinol-binding protein 4. CONCLUSION: Our data suggest that an imbalance of aquaporin-4 in the cerebrospinal fluid of patients with idiopathic intracranial hypertension may contribute to the pathogenesis of this disorder. PMID- 26853805 TI - Gray matter changes related to medication overuse in patients with chronic migraine. AB - OBJECTIVE: The objective of this article is to investigate the neurological substrates associated with medication overuse (MO) in patients with chronic migraine (CM). METHODS: We recruited age- and sex-matched CM patients with MO (CMwMO), CM patients without MO (CMwoMO), and healthy controls (HCs). Magnetic resonance T1-weighted images were processed by voxel-based morphometry, and the findings were correlated with clinical variables and treatment responses. RESULTS: A total of 66 patients with CM (half with MO) and 33 HCs completed the study. Patients with CMwMO compared to the patients with CMwoMO showed gray matter volume (GMV) decrease in the orbitofrontal cortex and left middle occipital gyrus as well as GMV increase in the left temporal pole/parahippocampus. The GMV changes explained 31.1% variance of the analgesics use frequency. The patients who responded to treatment had greater GMV in the orbitofrontal cortex (p = 0.028). Patients with CM (with and without MO), compared with HCs, had decreased GMV at multiple brain areas including the frontal, temporal and occipital lobes, precuneus and cerebellum. CONCLUSIONS: Our study showed GMV changes in CMwMO patients compared to the CMwoMO patients. These three cerebral regions accounted for significant variance in analgesics use frequency. Moreover, the GMV of the orbitofrontal cortex was predictive of the response to MO treatments. PMID- 26853806 TI - Migraine is related to an increased risk of Parkinson's disease: A population based, propensity score-matched, longitudinal follow-up study. AB - BACKGROUND: The association between migraine and Parkinson's disease (PD) remains controversial. The purpose of the present population-based, propensity score matched follow-up study was to investigate whether migraineurs are at a higher risk of developing PD. METHODS: A total of 41,019 subjects aged between 40 and 90 years with at least two ambulatory visits with a diagnosis of migraine in 2001 were enrolled in the migraine group. A logistic regression model that included age, sex, pre-existing comorbidities and socioeconomic status as covariates was used to compute the propensity score. The non-migraine group consisted of 41,019 propensity score-matched, randomly sampled subjects without migraine. The PD-free survival rate were estimated using the Kaplan-Meier method. Stratified Cox proportional hazard regression was used to estimate the effect of migraine on the risk of developing PD. RESULTS: During follow-up, 148 subjects in the migraine group and 101 in the non-migraine group developed PD. Compared to the non migraine group, the hazard ratio of PD for the migraine group was 1.64 (95% confidence interval: 1.25-2.14, p = 0.0004). The PD-free survival rate for the migraine group was significantly lower than that for the non-migraine group (p = 0.0041). CONCLUSIONS: This study showed an increased risk of developing PD in patients with migraine. PMID- 26853807 TI - Arsenic hyperaccumulation induces metabolic reprogramming in Pityrogramma calomelanos to reduce oxidative stress. AB - Arsenic (As) pollution is a major environmental concern due to its worldwide distribution and high toxicity to organisms. The fern Pityrogramma calomelanos is one of the few plant species known to be able to hyperaccumulate As, although the mechanisms involved are largely unknown. This study aimed to investigate the metabolic adjustments involved in the As-tolerance of P. calomelanos. For this purpose, ferns with five to seven fronds were exposed to a series of As concentrations. Young fronds were used for biochemical analysis and metabolite profiling using gas chromatography-mass spectrometry. As treatment increased the total concentration of proteins and soluble phenols, enhanced peroxidase activities, and promoted disturbances in nitrogen and carbon metabolism. The reduction of the glucose pool was one of the striking responses to As. Remarkable changes in amino acids levels were observed in As-treated plants, including those related to biosynthesis of glutathione and phenols, osmoregulation and two photorespiratory intermediates. In addition, increases in polyamines levels and antioxidant enzyme activities were observed. In summary, this study indicates that P. calomelanos tolerates high concentration of As due to its capacity to upregulate biosynthesis of amino acids and antioxidants, without greatly disturbing central carbon metabolism. At extremely high As concentrations, however, this protective mechanism fails to block reactive oxygen species production, leading to lipid peroxidation and leaf necrosis. PMID- 26853808 TI - Exercise and physical activity recommendations for people with cerebral palsy. AB - Physical activity and its promotion, as well as the avoidance of sedentary behaviour, play important roles in health promotion and prevention of lifestyle related diseases. Guidelines for young people and adults with typical development are available from the World Health Organisation and American College of Sports Medicine. However, detailed recommendations for physical activity and sedentary behaviour have not been established for children, adolescents, and adults with cerebral palsy (CP). This paper presents the first CP-specific physical activity and exercise recommendations. The recommendations are based on (1) a comprehensive review and analysis of the literature, (2) expert opinion, and (3) extensive clinical experience. The evidence supporting these recommendations is based on randomized controlled trials and observational studies involving children, adolescents, and adults with CP, and buttressed by the previous guidelines for the general population. These recommendations may be used to guide healthcare providers on exercise and daily physical activity prescription for individuals with CP. PMID- 26853810 TI - Robust superhydrophobic surface on Al substrate with durability, corrosion resistance and ice-phobicity. AB - Practical application of superhydrophobic surfaces is limited by the fragility of nanoscale asperities. Combining chemical etching and anodization, microscale pits and nanoscale pores, instead of the micro and nano protrusions on traditional superhydrophobic surfaces mimicking Lutos leaves, were fabricated on commercially pure aluminum surfaces. After modified by FDTS, the surfaces were superhydrophobic and self-cleaning. The ultrahigh hardness and electrochemical stability of Al2O3 coating endowed the surface excellent mechanical durability and good corrosion resistance. Because the method is scalable, it may find practical application on body panels of automobiles and aircrafts and so on. PMID- 26853809 TI - Annexin A6 regulates interleukin-2-mediated T-cell proliferation. AB - Annexin A6 (AnxA6) has been implicated in cell signalling by contributing to the organisation of the plasma membrane. Here we examined whether AnxA6 regulates signalling and proliferation in T cells. We used a contact hypersensitivity model to immune challenge wild-type (WT) and AnxA6(-/-) mice and found that the in vivo proliferation of CD4(+) T cells, but not CD8(+) T cells, was impaired in AnxA6(-/ ) relative to WT mice. However, T-cell migration and signalling through the T cell receptor ex vivo was similar between T cells isolated from AnxA6(-/-) and WT mice. In contrast, interleukin-2 (IL-2) signalling was reduced in AnxA6(-/-) compared with WT T cells. Further, AnxA6-deficient T cells had reduced membrane order and cholesterol levels. Taken together, our data suggest that AnxA6 regulates IL-2 homeostasis and sensitivity in T cells by sustaining a lipid raft like membrane environment. PMID- 26853812 TI - The importance of examining variants of implementation among evidence-based and promising programs to prevent child maltreatment. PMID- 26853811 TI - Annual decline in forced expiratory volume is steeper in aluminum potroom workers than in workers without exposure to potroom fumes. AB - BACKGROUND: Aluminum potroom exposure is associated with increased mortality of COPD but the association between potroom exposure and annual decline in lung function is unknown. We have measured lung volumes annually using spirometry from 1986 to 1996. The objective was to compare annual decline in forced expiratory volume in 1 s (dFEV1) and forced vital capacity (dFVC). METHODS: The number of aluminum potroom workers was 4,546 (81% males) and the number of workers in the reference group was 651 (76% males). The number of spirometries in the index group and the references were 24,060 and 2,243, respectively. RESULTS: After adjustment for confounders, the difference in dFEV1 and dFVC between the index and reference groups were 13.5 (P < 0.001) and -8.0 (P = 0.060) ml/year. CONCLUSION: Aluminum potroom operators have increased annual decline in FEV1 relative to a comparable group with non-exposure to potroom fumes and gases. PMID- 26853813 TI - Salivary melatonin levels and sleep-wake rhythms in pregnant women with hypertensive and glucose metabolic disorders: A prospective analysis. AB - In preeclampsia and gestational diabetes, the sympathetic nerves are activated, leading to disrupted sleep. Melatonin, which transmits information to regulate the sleep-wake rhythm and other such biorhythms, has been implicated in insulin resistance, antioxidant behaviors, and metabolic syndrome. In addition, its reduced secretion increases the risk of hypertension and diabetes. The aim of this study was to elucidate the features of melatonin secretion, sleep quality, and sleep-wake rhythms in pregnant women with complications. Fifty-eight pregnant women with pregnancy complications (hypertensive or glucose metabolic disorders) and 40 healthy pregnant women completed questionnaires, including sleep logs and the Pittsburgh Sleep Quality Index (PSQI), during the second to third trimesters. Their salivary melatonin levels were also measured. Pregnant women with complications had significantly lower morning (p < 0.001), daytime (p < 0.01), evening (p < 0.001), night (p < 0.01), daily mean (p < 0.001), peak (p < 0.001), and bottom (p < 0.01) melatonin values than healthy pregnant women. Pregnant women with complications also had significantly smaller melatonin amplitudes than healthy pregnant women (p < 0.001). Among pregnant women with complications, the duration (p < 0.05) and frequency (p < 0.01) of wake after sleep-onset were significantly greater in the poor sleep group than in the favorable sleep group which was divided by PSQI cutoff value. Pregnant women with hypertensive or glucose metabolic disorder complications had smaller circadian variation in salivary melatonin secretion, and their values were lower throughout the day than healthy pregnant women. PMID- 26853814 TI - The effect of dietary intake of sesame (Sesamumindicum L.) derivatives related to the lipid profile and blood pressure: A systematic review. AB - In this systematic review, we discuss the scientific evidence about the effect of dietary intake of seeds and sesame derivatives on lipid profile and blood pressure (BP) of hypertensive and dyslipidemic individuals. Clinical trials published in English, Portuguese or Spanish were searched on the following databases: Lilacs, PubMed, Isi Web of Knowledge, Cochrane Library, Scopus, Trip Data Base and Scielo. The bibliographic search period was started in September 2013 and ended in January 2014. The biases of risk analysis were carried out considering 6 of the 8 criteria of the Cochrane Handbook for Systematic Reviews of Interventions Version 5.1. Of the 7 clinical trials included, five evaluating individuals with hypertension observed a significant reduction in systolic and/or diastolic blood pressure. The two articles that evaluated individuals with dyslipidemia showed improvement in lipid profile. The mechanisms of action are still being studied. Regarding the bias risk analysis, clinical trials included showed few descriptions of the methods applied. There are few studies about sesame ingestion, and it was observed high risk for bias in the selected studies. More standardized methods with attention to the design of studies are needed to improve the level of the evidence. PMID- 26853815 TI - Emotional states as mediators between tinnitus loudness and tinnitus distress in daily life: Results from the "TrackYourTinnitus" application. AB - The psychological process how tinnitus loudness leads to tinnitus distress remains unclear. This cross-sectional study investigated the mediating role of the emotional state "stress level" and of the two components of the emotional state "arousal" and "valence" with N = 658 users of the "TrackYourTinnitus" smartphone application. Stress mediated the relationship between tinnitus loudness and tinnitus distress in a simple mediation model and even in a multiple mediation model when arousal and valence were held constant. Arousal mediated the loudness-distress relationship when holding valence constant, but not anymore when controlling for valence as well as for stress. Valence functioned as a mediator when controlling for arousal and even when holding arousal and stress constant. The direct effect of tinnitus loudness on tinnitus distress remained significant in all models. This study demonstrates that emotional states affect the process how tinnitus loudness leads to tinnitus distress. We thereby could show that the mediating influence of emotional valence is at least equally strong as the influence of stress. Implications of the findings for future research, assessment, and clinical management of tinnitus are discussed. PMID- 26853816 TI - Applying animal-based welfare assessments on New Zealand dairy farms: feasibility and a comparison with United Kingdom data. AB - AIMS: To assess the feasibility of applying animal-based welfare assessments developed for use in Europe on New Zealand dairy farms; in particular, to identify measures which could be evaluated during a single visit at milking time alongside whole herd locomotion scoring. METHODS: A protocol for animal welfare assessment, developed in the United Kingdom (UK), was evaluated. Measures that were suitable for use on pasture-based dairy farms in New Zealand were then assessed for practicability on 59 farms across New Zealand, during and immediately after milking, alongside whole herd locomotion scoring. Where data were collected the results were compared to those from a UK study of 53 dairy farms. RESULTS: Thirteen observations of the physical condition of cows were considered suitable for measurement, excluding observations related to hock lesions as they are rarely observed on pasture-based farms. Five of these measures were not assessed as there was not time to do so during milking alongside whole herd locomotion scoring. Thus, the prevalence of dirty flanks, hind limbs and udders, dull coat, thick hairy coat, significant hair loss, very fat cows (body condition score (BCS) >=7 on 1-10 scale) and very thin cows (BCS<=3), were recorded. Three measures of behaviour were considered suitable for measurement on-farm, but only locomotion score was practicable and was measured. Farmer-estimates for the incidence of mastitis, lameness, sudden death, milk fever and other diseases were also obtained.Overall, dirty flanks, dirty udders and estimated milk fever incidence were more prevalent in this study than in the UK. The prevalence of thin and fat cows, lame cows and estimated mastitis incidence were much lower in the present study than on UK farms. CONCLUSIONS AND CLINICAL RELEVANCE: Animal-based assessments can be used on dairy farms in New Zealand, but need to be modified from those developed for housed cows.Welfare on these farms was generally good compared to those in the UK, but these results need to be confirmed on more farms using a wider range of assessments than proved practicable in this study. PMID- 26853817 TI - Characterization of a novel Kazal-type serine proteinase inhibitor of Arabidopsis thaliana. AB - Many different types of serine proteinase inhibitors have been involved in several kinds of plant physiological processes, including defense mechanisms against phytopathogens. Kazal-type serine proteinase inhibitors, which are included in the serine proteinase inhibitor family, are present in several organisms. These proteins play a regulatory role in processes that involve serine proteinases like trypsin, chymotrypsin, thrombin, elastase and/or subtilisin. In the present work, we characterized two putative Kazal-type serine proteinase inhibitors from Arabidopsis thaliana, which have a single putative Kazal-type domain. The expression of these inhibitors is transiently induced in response to leaf infection by Botrytis cinerea, suggesting that they play some role in defense against pathogens. We also evaluated the inhibitory specificity of one of the Kazal-type serine proteinase inhibitors, which resulted to be induced during the local response to B. cinerea infection. The recombinant Kazal-type serine proteinase inhibitor displayed high specificity for elastase and subtilisin, but low specificity for trypsin, suggesting differences in its selectivity. In addition, this inhibitor exhibited a strong antifungal activity inhibiting the germination rate of B. cinerea conidia in vitro. Due to the important role of proteinase inhibitors in plant protection against pathogens and pests, the information about Kazal-type proteinase inhibitors described in the present work could contribute to improving current methods for plant protection against pathogens. PMID- 26853818 TI - Effects of elevated growth temperature and heat shock on the lipid composition of the inner and outer membranes of Yersinia pseudotuberculosis. AB - Differences in the distribution of individual phospholipids between the inner (IM) and outer membranes (OM) of gram-negative bacteria have been detected in mesophilic Escherichia, Erwinia and Salmonella species but have never been investigated in the psychrotrophic Yersinia genus. Therefore, the influence of an elevated growth temperature and heat shock on the phospholipid and fatty acid (FA) compositions of the fractionated Yersinia pseudotuberculosis envelope was investigated. The shift of the growth temperature from 8 degrees C to 37 degrees C to mimic the switch from saprophytic to parasitic growth of this bacteria and the exposure of the cells to heat shock, which was induced by a sharp increase in the temperature from 8 degrees C to 45 degrees C, increased the lysophosphatidylethanolamine content from zero and 1% to 6% and 10% in the IM and OM, respectively. These changes were accompanied by a decrease in the phosphatidylethanolamine (PE) content and a drastic increase (up to 3-fold higher) in the phosphatidylglycerol (PG) level in the OM of the bacteria, which increases the net negative charge of the cell envelope. The levels of the predominant saturated palmitic (16:0) and cyclopropane FAs were approximately 1.5 and 7.5-fold higher, respectively, but the content of the predominant unsaturated palmitoleic (16:1n-7) and cis-vaccenic (18:1n-7) FAs was approximately 10-30-fold lower in both membranes that were isolated from the cells grown at elevated temperatures. Due to these changes, reflecting the process of "homeoviscous adaptation", the ratio between the unsaturated and saturated FAs decreased but remained higher in the IM than that in the OM. Simultaneously, no significant changes were observed in the FA composition of cells subjected to heat shock, demonstrating a difference between the responses of the heat-shocked and heat-adapted Y. pseudotuberculosis. The unique ability of Y. pseudotuberculosis to reciprocally regulate the ratio of anionic PG and net neutral PE and therefore adjust the negative charge of the OM may be a common strategy used by pathogenic bacteria to promote the barrier function of the OM. PMID- 26853819 TI - MTHFD1 regulates nuclear de novo thymidylate biosynthesis and genome stability. AB - Disruptions in folate-mediated one-carbon metabolism (FOCM) are associated with risk for several pathologies including developmental anomalies such as neural tube defects and congenital heart defects, diseases of aging including cognitive decline, neurodegeneration and epithelial cancers, and hematopoietic disorders including megaloblastic anemia. However, the causal pathways and mechanisms that underlie these pathologies remain unresolved. Because folate-dependent anabolic pathways are tightly interconnected and best described as a metabolic network, the identification of causal pathways and associated mechanisms of pathophysiology remains a major challenge in identifying the contribution of individual pathways to disease phenotypes. Investigations of genetic mouse models and human inborn errors of metabolism enable a more precise dissection of the pathways that constitute the FOCM network and enable elucidation of causal pathways associated with NTDs. In this overview, we summarize recent evidence that the enzyme MTHFD1 plays an essential role in FOCM in humans and in mice, and that it determines the partitioning of folate-activated one carbon units between the folate-dependent de novo thymidylate and homocysteine remethylation pathways through its regulated nuclear localization. We demonstrate that impairments in MTHFD1 activity compromise both homocysteine remethylation and de novo thymidylate biosynthesis, and provide evidence that MTHFD1-associated disruptions in de novo thymidylate biosynthesis lead to genome instability that may underlie folate-associated immunodeficiency and birth defects. PMID- 26853820 TI - EEG frequency tagging to explore the cortical activity related to the tactile exploration of natural textures. AB - When sliding our fingertip against a textured surface, complex vibrations are produced in the skin. It is increasingly recognised that the neural transduction and processing of these vibrations plays an important role in the dynamic tactile perception of textures. The aim of the present study was to develop a novel means to tag the cortical activity related to the processing of these vibrations, by periodically modulating the amplitude of texture exploration-induced vibrations such as to record a steady-state evoked potential (SS-EP). The EEG was recorded while the right index fingertip was scanned against four different textures using a constant exploration velocity. Amplitude modulation of the elicited vibrations was achieved by periodically modulating the force applied against the finger. Frequency analysis of the recorded EEG signals showed that modulation of the vibrations induced by the fingertip-texture interactions elicited an SS-EP at the frequency of modulation (3 Hz) as well as its second harmonic (6 Hz), maximal over parietal regions contralateral to the stimulated side. Textures generating stronger vibrations also generated SS-EPs of greater magnitude. Our results suggest that frequency tagging using SS-EPs can be used to isolate and explore the brain activity related to the tactile exploration of natural textures. PMID- 26853821 TI - Benefits of pazopanib over sunitinib for renal cell carcinoma. PMID- 26853822 TI - Link between rosacea and glioma in nationwide cohort. PMID- 26853823 TI - Characterization of chitosan-nanoclay bionanocomposite active films containing milk thistle extract. AB - Nowadays, bio-based and antioxidant active packaging is attracting significant attention as one of the preferred emerging technologies to prevent sensitive oxidation of foods. In this study, chitosan/nanoclay nanocomposite active films containing three different levels of sodium montmorillonite (MMT) (1, 3 and 5% w/w based on chitosan) and Silybum marianum L. extract (SME) (0.5, 1 and 1.5% v/v) were prepared. The obtained films were characterized in terms of structural, thermal, mechanical, and barrier properties as well as antioxidant behavior. X ray diffraction patterns confirmed the exfoliated dispersion form of MMT nanolayers. Scanning electron microscopy images showed an increase in films' surface roughness by the addition of MMT. The results indicated that water vapor permeability and solubility of films reduced significantly (p<0.05) by incorporation of MMT and SME. The mechanical and optical properties of films were significantly affected by the content of MMT and SME (p<0.05). Antioxidant properties of the films also were improved by SME incorporation, suggesting that the formulated bionanocomposites could be considered as a promising antioxidant active packaging material. PMID- 26853824 TI - A polysaccharide isolated from Cynomorium songaricum Rupr. protects PC12 cells against H2O2-induced injury. AB - As a great deal of interest is developed to study novel bioactive components with health benefit effects from natural resources, in this paper, a rat pheochromocytoma line 12 (PC12) cell is built to observe the protective effect of a Cynomorium songaricum Rupr. polysaccharide (CSP) against H2O2-induced oxidative stress. Fluorescence microscope, flow cytometry and micro-plate reader are used to assess cell viability and apoptosis. And the levels of reactive oxygen species (ROS), 8-hydroxy-2'-deoxyguanosine (8-OH-dG), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and lactate dehydrogenase (LDH) are evaluated. The results show that, the CSP can significantly protect PC12 cells against H2O2-induced oxidative stress, increase the intracellular antioxidase system load and inhibit H2O2-induced apoptosis by scavenging of ROS, regulating cell cycle, preventing DNA damage and protecting the cell membrane. This research would be benefit for preventing and curing the oxidation-related diseases in polysaccharide study. PMID- 26853825 TI - Immunomodulatory and antioxidative activity of Cordyceps militaris polysaccharides in mice. AB - To evaluate the immune activation and reactive oxygen species scavenging activity of Cordyceps militaris polysaccharides (CMP) in vivo, 24 male and 24 female Kunming mice were randomly divided into four groups. The mice in the four experimental groups were administered 0 (normal control), 50, 100, or 200mg/kg/d body weight CMP via gavage. After 30 days, the viscera index, leukocyte count, differential leukocyte count, immunoglobulin (IgG) levels, and biochemical parameters were measured. The effect of CMP on the expression of tumor necrosis (TNF)-alpha, interferon (IFN)-gamma, and interleukin (IL)-1beta in the spleens of experimental mice was investigated by real-time polymerase chain reaction. The results showed that the administration of CMP improved the immune function in mice, significantly increased the spleen and thymus indices, the spleen lymphocyte activity, the total quantity of white blood cells, and IgG function in mice serum. CMP exhibited significant antioxidative activity in mice, and decreased malondialdehyde levels in vivo. CMP upregulated the expression of TNF alpha, IFN-gamma, and IL-1beta mRNA in high-dose groups compared to that observed for the control mice. We can thus conclude that CMP effectively improved the immune function through protection against oxidative stress. CMP thus shows potential for development as drugs and health supplements. PMID- 26853826 TI - Checking for reversibility of aggregation of UV-irradiated glycogen phosphorylase b under crowding conditions. AB - It is believed that the initial stages of protein aggregation are reversible and can be reversed by simple dilution, whereas prolonged exposure to factors responsible for denaturing proteins (for example, to elevated temperatures) results in the formation of irreversible aggregates. A new approach has been developed to discriminate the stage of the formation of reversible aggregates. Aggregation of UV-irradiated glycogen phosphorylase b (UV-Phb) was studied at 10, 25 and 37 degrees C in the presence of crowders (polyethylene glycol and Ficoll 70) using dynamic light scattering and analytical ultracentrifugation (pH 6.8; 0.1M NaCl). The dilution of the protein solution in the course of aggregation at 10 degrees C results in the breakdown of protein aggregates suggesting that the aggregation process is reversible. When aggregation of UV-Phb is studied at 37 degrees C, reversibility is lacking. Chemical chaperones (arginine, proline) induce the breakdown of protein aggregates of UV-Phb formed at 10 degrees C. In the experiments carried out at 37 degrees C in the presence of crowder the addition of arginine results in disintegration of protein aggregates only at early stages of the aggregation process. It is assumed that general pathway of protein aggregation includes the formation of reversible, completely dissociable, partly dissociable and irreversible aggregates. PMID- 26853827 TI - CC5 and CC8, two homologous disintegrins from Cerastes cerastes venom, inhibit in vitro and ex vivo angiogenesis. AB - Angiogenesis constitutes a fundamental step in tumor progression. Thus, targeting tumour angiogenesis has been identified to be promising in cancer treatment. In this work, CC5 and CC8, two highly homologous disintegrins isolated from the venom Cerastes cerastes viper from the south of Tunisia, were assessed for their anti-angiogenic effect by testing their ability to interfere with viability, adhesion, migration and angiogenesis of Human Microvascular Endothelial Cells, HMEC-1 and HBMEC. We found that CC5 and CC8 displayed pro-apoptotic potential in HMEC-1 cells. Anoikis like induced by these two disintegrins was evidenced by cell detachment, down regulation of FAK/AKT/PI3K axis and caspase activation. In addition, both CC5 and CC8 exhibited in vitro anti-adhesive, anti-migratory and anti-proliferative effects on endothelial cells HBMEC. These effects appeared to require RGD and/or WGD loops disintegrin. CC5 and CC8 also inhibited tube formation on matrigel and displayed potent anti-angiogenic activities as assessed ex vivo, using both the embryo chick chorioallantoic membrane model (CAM) and rat aortic ring assay. Altogether our results demonstrate that CC5 and CC8, are potent inhibitors of angiogenesis, by disrupting alphavbeta3 and alpha5beta1 binding. The use of CC5 and/or CC8 could provide a beneficial tool to inhibit abnormal angiogenesis and to induce cancer regression. PMID- 26853828 TI - Assessment of noise exposure for basketball sports referees. AB - Dosimetric measurements carried out on basketball referees have shown that whistles not only generate very high peak sound pressure levels, but also play a relevant role in determining the overall exposure to noise of the exposed subjects. Because of the peculiar geometry determined by the mutual positions of the whistle, the microphone, and the ear, experimental data cannot be directly compared with existing occupational noise exposure and/or action limits. In this article, an original methodology, which allows experimental results to be reliably compared with the aforementioned limits, is presented. The methodology is based on the use of two correction factors to compensate the effects of the position of the dosimeter microphone (fR) and of the sound source (fS). Correction factors were calculated by means of laboratory measurements for two models of whistles (Fox 40 Classic and Fox 40 Sonik) and for two head orientations (frontal and oblique).Results sho w that for peak sound pressure levels the values of fR and fS, are in the range -8.3 to -4.6 dB and -6.0 to -1.7 dB, respectively. If one considers the Sound Exposure Levels (SEL) of whistle events, the same correction factors are in the range of -8.9 to -5.3 dB and -5.4 to -1.5 dB, respectively. The application of these correction factors shows that the corrected weekly noise exposure level for referees is 80.6 dB(A), which is slightly in excess of the lower action limit of the 2003/10/EC directive, and a few dB below the Recommended Exposure Limit (REL) proposed by the National Institute for Occupational Safety and Health (NIOSH). The corrected largest peak sound pressure level is 134.7 dB(C) which is comparable to the lower action limit of the 2003/10/EC directive, but again substantially lower than the ceiling limit of 140 dB(A) set by NIOSH. PMID- 26853829 TI - Three-dimensional imaging: a novel, valid, and reliable technique for measuring wound surface area. AB - PURPOSE: The aim of this study was to investigate the validity and reliability of a novel three-dimensional imaging technique using Artec MHTTM 3D Scanner for measuring the wound surface area. METHODS: The validity was tested by measuring the surface area of 60 stickers (gold standard) on 20 volunteers. Stickers with standardized areas of 2590, 7875, and 15,540 mm2 were applied on the thorax, forearm, and thigh, respectively. For the reliability test, 58 burn wounds on 48 patients were assessed twice by two different observers with the Artec MHTTM 3D Scanner. Scanning, post-processing, and surface area measurements were performed by two clinicians. RESULTS: The results for the validity analysis showed an intraclass correlation coefficient of 0.99 and coefficient of variation of the thorax, forearm, and thigh were 1.1%, 0.9%, and 0.6%, respectively. The reliability analysis showed an intraclass correlation coefficient of 0.99, a coefficient of variation of 6.3%, and limits of agreement between measurements of two observers were calculated at 0 +/- 0.17 * mean surface area. CONCLUSION: Three-dimensional imaging using the Artec MHTTM 3D Scanner is a valid and reliable method for measuring the wound surface area. PMID- 26853830 TI - Noise Reduction in Complex Biological Switches. AB - Cells operate in noisy molecular environments via complex regulatory networks. It is possible to understand how molecular counts are related to noise in specific networks, but it is not generally clear how noise relates to network complexity, because different levels of complexity also imply different overall number of molecules. For a fixed function, does increased network complexity reduce noise, beyond the mere increase of overall molecular counts? If so, complexity could provide an advantage counteracting the costs involved in maintaining larger networks. For that purpose, we investigate how noise affects multistable systems, where a small amount of noise could lead to very different outcomes; thus we turn to biochemical switches. Our method for comparing networks of different structure and complexity is to place them in conditions where they produce exactly the same deterministic function. We are then in a good position to compare their noise characteristics relatively to their identical deterministic traces. We show that more complex networks are better at coping with both intrinsic and extrinsic noise. Intrinsic noise tends to decrease with complexity, and extrinsic noise tends to have less impact. Our findings suggest a new role for increased complexity in biological networks, at parity of function. PMID- 26853831 TI - Case series of patients with Fusobacterium nucleatum bacteremia with emphasis on the presence of cancer. AB - Fusobacterium nucleatum is anaerobic oral microbiota that might be associated with cancer. We reported 22 consecutive cases of patients (mean age of 63.8 years (range 34-89), 59.1% male) with F. nucleatum bacteremia that were admitted to a university hospital over a 10-year period. In 17 (77.2%) of these patients, F. nucleatum was the sole possible pathogen. Seven of the 22 patients (31.8%) had active cancer: esophagus carcinoma (n = 3), hematologic malignancies (n = 1), gastrointestinal stromal tumor (n = 1), melanoma (n = 1), and breast cancer (n = 1). In six out of seven patients (85.7%), the F. nucleatum was found within six months of the diagnosis of cancer. Four of seven (57.1%), patients with cancer were on chemotherapy. Three of 22 patients (13.4%) died within 1 month of F. nucleatum bacteremia due to cancer. In conclusion, F. nucleatum bacteremia occurs rarely and when it is found, it is often in patients with cancer, especially those with a recent diagnosis. PMID- 26853832 TI - Gas-Phase Folding of a Prototypical Protonated Pentapeptide: Spectroscopic Evidence for Formation of a Charge-Stabilized beta-Hairpin. AB - Ultraviolet and infrared-ultraviolet (IR-UV) double-resonance photofragment spectroscopy has been carried out in a tandem mass spectrometer to determine the three-dimensional structure of cryogenically cooled protonated C-terminally methyl esterified leucine enkephalin [YGGFL-OMe+H](+). By comparing the experimental IR spectrum of the dominant conformer with the predictions of DFT M05-2X/6-31+G(d) calculations, a backbone structure was assigned that is analogous to that previously assigned by our group for the unmodified peptide [ Burke, N.L.; et al. Int. J. Mass Spectrom. 2015 , 378 , 196 ], despite the loss of a C-terminal OH binding site that was thought to play an important role in its stabilization. Both structures are characterized by a type II' beta-turn around Gly(3)-Phe(4) and a gamma-turn around Gly(2), providing spectroscopic evidence for the formation of a beta-hairpin hydrogen bonding pattern. Rather than disrupting the peptide backbone structure, the protonated N-terminus serves to stabilize the beta-hairpin by positioning itself in a pocket above the turn where it can form H-bonds to the Gly(3) and C-terminus C?O groups. This beta-hairpin type structure has been previously proposed as the biologically active conformation of leucine enkephalin and its methyl ester in the nonpolar cell membrane environment [ Naito, A.; Nishimura, K. Curr. Top. Med. Chem. 2004 , 4 , 135 - 143 ]. PMID- 26853833 TI - A preliminary examination of over-the-counter medication misuse rates in older adults. AB - BACKGROUND: Older adults are the largest consumers of over the counter (OTC) medications. Of the older adults who are at risk of a major adverse drug event, more than 50% of these events involve an OTC medication. OBJECTIVE: To explore how older adults select and hypothetically use OTC medications and if the selected medications would be considered safe for use. METHODS: Walking interviews were conducted with 20 community-dwelling older adults in a community pharmacy. Each participant selected an OTC medication for a hypothetical pain and sleep scenario. Data were analyzed for four types of misuse: drug-drug interaction, drug-disease interaction, drug-age interaction, and excess usage. RESULTS: At least one instance of potential misuse was found in 95% of participants. For sleep medications, drug-drug interactions and drug-age interactions were more common, affecting 50% and 65% of participants respectively. The most common type of misuse noted in the pain products selected was that of drug-drug interaction, with a total of 39 occurrences, affecting 60% of the participants. CONCLUSIONS: OTC misuse is common among older adults, and it is important for older adults to seek out resources, such as a pharmacist, to help them make safe OTC decisions. PMID- 26853834 TI - Initial development of the Systems Approach to Home Medication Management (SAHMM) model. AB - BACKGROUND: Adverse drug events and medication nonadherence are two problems associated with prescription medication use for chronic conditions. These issues often develop because patients have difficulty managing their medications at home. To guide patients and providers for achieving safe and effective medication use at home, the Systems Approach to Home Medication Management (SAHMM) model was derived from a systems engineering model for health care workplace safety. OBJECTIVE: To explore how well concepts from the SAHMM model can represent home medication management by using patient descriptions of how they take prescription medications at home. METHODS: Twelve patients were interviewed about home medication management using an interview guide based on the factors of the SAHMM model. Each interview was audio-taped and then transcribed verbatim. Interviews were coded to identify themes for home medication management using MAXQDA for Windows. RESULTS: SAHMM concepts extracted from the coded interview transcripts included work system components of person, tasks, tools & technology, internal environment, external environment, and household. Concepts also addressed work processes and work outcomes for home medication management. CONCLUSIONS: Using the SAHMM model for studying patients' home medication management is a promising approach to improving our understanding of the factors that influence patient adherence to medication and the development of adverse drug events. PMID- 26853835 TI - Glycopeptide-functionalized gold nanoparticles for antibody induction against the tumor associated mucin-1 glycoprotein. AB - We report the preparation of gold nanoparticle (AuNP)-based vaccine candidates against the tumor-associated form of the mucin-1 (MUC1) glycoprotein. Chimeric peptides, consisting of a glycopeptide sequence derived from MUC1 and the T-cell epitope P30 sequence were immobilized on PEGylated AuNPs and the ability to induce selective antibodies in vivo was investigated. After immunization, mice showed significant MHC-II mediated immune responses and their antisera recognized human MCF-7 breast cancer cells. Nanoparticles designed according to this report may become key players in the development of anticancer vaccines. PMID- 26853836 TI - Synthesis and cytotoxicity of thieno[2,3-b]quinoline-2-carboxamide and cycloalkyl[b]thieno[3,2-e]pyridine-2-carboxamide derivatives. AB - Seventy nine derivatives of thieno[2,3-b]quinolines, tetrahydrothieno[2,3 b]quinoline, dihydrocyclopenta[b]thieno[3,2-e]pyridine, cyclohepta[b]thieno[3,2 e]pyridine and hexahydrocycloocta[b]thieno[3,2-e]pyridine were either synthesized or obtained commercially and tested for their antiproliferative activity against HCT116, MDA-MB-468 and MDA-MB-231 human cancer cell lines. The most potent eight compounds were active against all cell lines with IC50 values in the 80-250nM range. In general hexahydrocycloocta[b]thieno[3,2-e]pyridines were most active with increasing activity observed as larger cycloalkyl rings were fused to the pyridine ring. PMID- 26853837 TI - Globulispora mitoportans n. g., n. sp., (Opisthosporidia: Microsporidia) a microsporidian parasite of daphnids with unusual spore organization and prominent mitosome-like vesicles. AB - The microsporidian parasite Globulispora mitoportans, n. g., n. sp., infects the intestinal epithelium of two species of daphnids (Crustacea: Cladocera). Mature spores are thin-walled and possess a novel type of polaroplast with a conspicuous part consisting of globules that occupies a large part of the spore volume. Both developmental stages and the spores possess large, electron-lucent vesicles enveloped by a double membrane and filled with an internal web of filamentous material, corresponding structurally to microsporidian mitosomes. The SSU rRNA phylogeny places Globulispora into a specific "Enterocytospora-like" clade, part of a large "non-enterocytozoonidae" clade, grouping a heterogenous assemblage of microsporidia infecting almost exclusively insects and crustacea. PMID- 26853838 TI - Phase behavior, intermolecular interaction, and solid state characterization of amorphous solid dispersion of Febuxostat. AB - The aim of this work was to prepare and characterize the amorphous molecular dispersion of Febuxostat (FXT) using PVP K30, HPMC-AS, Soluplus(r), and PVP VA64. The solid dispersions were prepared by solvent evaporation technique. Their physical properties were studied by differential scanning calorimetry, powder X ray diffraction, Fourier transformation infrared spectroscopy, and compared to that of same physical mixtures. The success of physicochemical stability of the dispersions is often revealed as glass transition temperature (Tg) versus composition (w) dependencies. The shape of the Tg versus composition was mathematically modeled using the Gordon-Taylor equation, Couchman-Karasz equation, Brekner-Schneider-Cantow equation, and a three-parameter BCKV equation. In this work, different types of Tg patterns obtained for FXT-polymer binary mixtures are analyzed in terms of the above equations and relations between their prime fitting parameters are presented. The theoretical values and modeled parameters were compared using various results obtained by thermal analysis. The influence of important physicochemical phenomena and properties of the mixtures on the shape of the Tg versus composition patterns are also illustrated. The interaction between drug and polymers and the model parameters were analyzed, aiming to assess the state of mixing and intermolecular interactions. PMID- 26853839 TI - The facile synthesis of chitosan-based silver nano-biocomposites via a solution plasma process and their potential antimicrobial efficacy. AB - Silver nanoparticles (AgNPs) were synthesized in a chitosan matrix with varying AgNO3 (1, 3, 5 mM) and chitosan (1, 3%) concentrations via the one-step solution plasma process (SPP). Plasma was discharged for 3 min in the AgNO3 and chitosan solutions using unipolar power at 800 V with a frequency of 30 kHz. Fibrous 3D scaffolds were prepared by lyophilizing the nano-biocomposite solutions, and they were stabilized via cross-linking with UV irradiation. UV-Vis spectroscopy showed strong peaks with maximal absorbance at 415-440 nm, indicating the formation of AgNPs in the chitosan with an increase in peak height as the concentration of the precursor, AgNO3, increased. The chemical association between AgNPs and chitosan was confirmed using Fourier transform infrared spectroscopy (FTIR). The scaffolds had a micro-porous structure with pore diameters in the range of 5.8-157.0 MUm, and a transmission electron microscopy (TEM) analysis revealed that spherical shaped AgNPs with diameters in the range of 2.5-27.6 nm were well-dispersed in the biocomposites. The nano-biocomposites had a broad spectrum of antimicrobial activity against various pathogens with minimal inhibition concentrations of 0.68 2.71 and 2.71-10.80 MUg mL(-1) for bacteria and fungi, respectively. These are the lowest concentrations achieved by nano-biocomposites reported thus far. The SPP was shown to be a facile, effective, and eco-friendly method of synthesizing nano-biocomposites for biomedical applications. PMID- 26853840 TI - Gene therapy strategies to improve strength and quality of flexor tendon healing. AB - INTRODUCTION: Rupture of the repair and adhesion around a tendon are two major problems after tendon surgery. Novel biological therapies which enhance healing and reduce adhesions are goals of many investigations. Gene therapy offers a new and promising approach to tackle these difficult problems. In the past decade, we sought to develop methods to augment tendon healing and reduce tendon adhesion through gene therapy. AREAS COVERED: This review discusses the methods and results of adeno-associated viral (AAV) type 2 vector gene therapy to increase tendon healing strength and reduce adhesions in a chicken model. Micro-RNA related gene therapy is also discussed. We also developed a controlled release system, which incorporates nanoparticles to deliver micro-RNAs to regulate tendon healing. EXPERT OPINION: We obtained promising results of enhancement of tendon healing strength in a chicken model using AAV2-mediated gene transfer. AAV2 mediated micro-RNA transfer also limited adhesions around the tendon. Controlled release systems incorporating nanoparticles have ideally delivered genes to the healing tendons and resulted in a moderate (but incomplete) reduction of adhesions. It remains to be determined what the best doses are and what other factors are in play in adhesion formation. These are two targets in our future investigations. PMID- 26853842 TI - Why do motor neurons degenerate? Actualization in the pathogenesis of amyotrophic lateral sclerosis. AB - INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disease affecting motor neurons. Although a small proportion of ALS cases are familial in origin and linked to mutations in specific genes, most cases are sporadic and have a multifactorial aetiology. Some recent studies have increased our knowledge of ALS pathogenesis and raised the question of whether this disorder is a proteinopathy, a ribonucleopathy, an axonopathy, or a disease related to the neuronal microenvironment. DEVELOPMENT: This article presents a review of ALS pathogenesis. To this end, we have reviewed published articles describing either ALS patients or ALS animal models and we discuss how the main cellular pathways (gene processing, protein metabolism, oxidative stress, axonal transport, relationship with neuronal microenvironment) may be involved in motor neurons degeneration. CONCLUSIONS: ALS pathogenesis has not been fully elucidated. Recent studies suggest that although initial triggers may differ among patients, the final motor neurons degeneration mechanisms are similar in most patients once the disease is fully established. PMID- 26853841 TI - Responsiveness of PROMIS(r) Pediatric Measures to Hospitalizations for Sickle Pain and Subsequent Recovery. AB - BACKGROUND: The Patient-Reported Outcomes Measurement Information System((r)) (PROMIS((r)) ) created pediatric self-report scales measuring a variety of health attributes (domains), but their responsiveness to changes in health status has not yet been determined in children with sickle cell disease (SCD). PROCEDURE: A convenience cohort of symptomatic SCD children, aged 8-17 years, was asked to complete PROMIS pediatric scales at an initial clinic visit, at the end of a subsequent hospitalization for sickle pain, at a subsequent clinic visit or at home 2-3 weeks after hospitalization, and at a clinic visit 1-2 years after their initial assessment. RESULTS: A total of 121 participants (mean age 12.5 +/- 3.1 years, 56.2% female) participated in the study. Pain interference and fatigue domain scores were elevated at baseline, increased substantially during hospitalization, and largely returned to baseline by the recovery period, whereas the depressive symptoms, anger, and anxiety domain scores displayed a less pronounced elevation during hospitalizations and a slower return to baseline levels. The two physical functioning scales showed a substantial decline in response to hospitalization, but only modest improvements at the recovery assessment, likely representing incomplete recovery. CONCLUSIONS: Several PROMIS pediatric measures were responsive to changes in health status associated with occurrence and resolution of acute vaso-occlusive pain requiring hospitalization. The substantial differences in these domains during SCD-related pain exacerbations support their potential usefulness in clinical research or in clinical practice. Further studies to characterize variations in symptom patterns over time may provide insights into strategies for more effective management of sickle pain. PMID- 26853844 TI - The use of food waste as a carbon source for on-site treatment of nutrient-rich blackwater from an office block. AB - Wastewater from office blocks is typically dominated by blackwater and is therefore concentrated and nutrient-rich. A pilot plant was operated for 260 days, receiving 300 L d(-1) of wastewater directly from an office building to determine whether nutrient removal could be achieved using food waste (FW) as a supplemental carbon source. The pilot plant consisted of a 600 L prefermenter and a 600 L membrane bioreactor that was operated as a sequential batch reactor in order to cycle through anoxic, anaerobic and aerobic phases. The influent wastewater Chemical Oxygen Demand (COD)/N/P was, on average, 1438/275/40 mg L( 1), considerably higher than typical municipal wastewater. Treatment trials on the wastewater alone showed that the COD was only marginally sufficient to exhaust nitrate, and initiate anaerobic conditions required for phosphate removal. The addition of 15 kg d(-1) of macerated FW increased the average influent COD/N/P concentrations to 20,072/459/66 mg L(-1). The suitability of FW as a carbon source was demonstrated by denitrification to NOx-N concentration of <1 mg L(-1) during the biological nutrient removal (BNR) cycles. N removal was limited by nitrification. FW also induced the anaerobic phase within the BNR cycles necessary for P removal. The final average COD (non-recalcitrant)/N/P effluent concentrations under FW supplementation were 7/50/13 mg L(-1) which equates to 99%, 89% and 80% COD/N/P removal, respectively, meeting the highest nutrient removal efficiency standards stipulated by state jurisdictions for on site systems in the USA. PMID- 26853843 TI - The relationship between the preoperative plasma level of HIF-1alpha and clinic pathological features, prognosis in non-small cell lung cancer. AB - Studies have found that hypoxia is the most common feature in all of solid tumor progression, thus it has become a central issue in tumor physiology and cancer treatment. Hypoxia-inducible factor-1alpha (HIF-1alpha) could make the tumor produce adaptive biological response to hypoxia and become more aggressive. In this paper, we used enzyme linked immune sorbent assay to detect the plasma level of HIF-1alpha in patients with NSCLC and healthy volunteers. The results indicated that the 5-year survival rate of patients with squamous cell carcinomas is negatively correlated with the plasma level of HIF-1alpha and the 5-year survival rate of patients with low level of HIF-1alpha is higher than those with high level of HIF-1alpha. The plasma level of HIF-1alpha in patients with NSCLC is significantly higher than healthy volunteers. There is no significant correlation between the plasma level of HIF-1alpha and clinical features of NSCLC patients. In a word, there is no connection between the plasma level of HIF 1alpha and the clinical features of NSCLC patients as well as their prognosis. In stratified analysis, the plasma level of HIF-1alpha in patients with squamous cell carcinoma is associated with regional lymph node status. PMID- 26853846 TI - Recovery of language function in Korean-Japanese crossed bilingual aphasia following right basal ganglia hemorrhage. AB - Few studies have investigated language recovery patterns and the mechanisms of crossed bilingual aphasia following a subcortical stroke. In particular, Korean Japanese crossed bilingual aphasia has not been reported. A 47-year-old, right handed man was diagnosed with an extensive right basal ganglia hemorrhage. He was bilingual, fluent in both Korean and Japanese. After his stroke, the patient presented with crossed aphasia. We investigated changes in the Korean (L1) and Japanese (L2) language recovery patterns. Both Korean and Japanese versions of the Western Aphasia Battery (WAB) were completed one month after the stroke, and functional magnetic resonance imaging (fMRI) was performed using picture-naming tasks. The WAB showed a paradoxical pattern of bilingual aphasia, with an aphasia quotient (AQ) of 32 for Korean and 50.6 for Japanese, with Broca's aphasia. The patient scored better in the Japanese version of all domains of the tests. The fMRI study showed left lateralized activation in both language tasks, especially in the inferior frontal gyrus. After six months of language therapy targeting L1, the Korean-WAB score improved significantly, while the Japanese-WAB score showed slight improvement. In this case, the subcortical lesion contributed to crossed bilingual aphasia more highly affecting L1 due to loss of the cortico-subcortical control mechanism in the dominant hemisphere. The paradoxical pattern of bilingual aphasia disappeared after lengthy language therapy targeting L1, and the therapy effect did not transfer to L2. Language recovery in L1 might have been accomplished by reintegrating language networks, including the contralesional language homologue area in the left hemisphere. PMID- 26853845 TI - Older Adult Falls Seen by Emergency Medical Service Providers: A Prevention Opportunity. AB - INTRODUCTION: Among people aged >=65 years, falling is the leading cause of emergency department visits. Emergency medical services (EMS) are often called to help older adults who have fallen, with some requiring hospital transport. Chief aims were to determine where falls occurred and the circumstances under which patients were transported by EMS, and to identify future fall prevention opportunities. METHODS: In 2012, a total of 42 states contributed ambulatory data to the National EMS Information System, which were analyzed in 2014 and 2015. Using EMS records from 911 call events, logistic regression examined patient and environmental factors associated with older adult transport. RESULTS: Among people aged >=65 years, falls accounted for 17% of all EMS calls. More than one in five (21%) of these emergency 911 calls did not result in a transport. Most falls occurred at home (60.2%) and residential institutions such as nursing homes (21.7%). Logistic regression showed AORs for transport were greatest among people aged >=85 years (AOR=1.14, 95% CI=1.13, 1.16) and women (AOR=1.30, 95% CI=1.29, 1.32); for falls at residential institutions or nursing homes (AOR=3.52, 95% CI=3.46, 3.58) and in rural environments (AOR=1.15, 95% CI=1.13, 1.17); and where the EMS impression was a stroke (AOR=2.96, 95% CI=2.11, 4.10), followed by hypothermia (AOR=2.36, 95% CI=1.33, 4.43). CONCLUSIONS: This study provides unique insight into fall circumstances and EMS transport activity. EMS personnel are in a prime position to provide interventions that can prevent future falls, or referrals to community-based fall prevention programs and services. PMID- 26853847 TI - Challenges and outcome of surgery for bowel obstruction in women with gynaecologic cancer. AB - INTRODUCTION: Bowel obstruction is associated with a reduction in quality of life and survival among cancer patients, and the entity is traditionally treated by general surgeons without dedication to the different malignancies that cause bowel obstruction or to palliation. This study aims to identify and improve outcome of bowel obstruction in women with a history of a gynaecologic cancer. METHODS: Women operated for bowel obstruction were screened for a history of gynaecologic cancer and their records were reviewed. RESULTS: Bowel obstruction followed cancer treatment by a median of 18.4 months (range 2.3-277) in 59 women. A malignant cause was identified in 53% and recurrence of cancer in 61%. The cause of malignant bowel obstruction was peritoneal carcinomatosis (19%), obstructing tumour and carcinomatosis (31%) and solitary tumour (3%). Ovarian cancer (OR: 6.29, 95% CI 1.95-20.21), residual tumour during initial surgery (R2 stage) (OR: 18.7, 96% CI: 4.35-80.46) and chemotherapy (OR: 7.19, 95% CI: 2.28 22.67) were all associated with malignant bowel obstruction. Surgery solved 84% of malignant bowel obstructions, but median survival was brief (2.5 months, 95% CI: 1.4-3.6) when compared to benign bowel obstruction (95.3 months, 64.7-125.9) (p < 0.001). Readmission for bowel obstruction occurred after a median of 4.3 months (95% CI: 3.1-5.5) in surviving patients with malignant bowel obstruction and after a median of 84.5 months (95% CI: 73.6-95.3) with adhesive obstruction (p < 0.001). CONCLUSIONS: Increased awareness of the aetiology to bowel obstruction may improve treatment strategy in these women. Women with malignant bowel obstruction should be carefully identified and differentiated in order to improve quality of life rather than pursuing emergency surgical procedures. PMID- 26853848 TI - Acquisition and Presentation of Tumor Antigens by Dendritic Cells. AB - Dendritic cells (DCs) are master regulators of the immune response and, because of their peculiar features in antigen acquisition, processing, and presentation, they play a critical role in activating an efficient antigenspecific T-lymphocyte response against tumors. However, the DC family is composed of different cell subsets, which may differently contribute to tumor-specific T-cell activation. In addition to the DC subset involved, the induction of a tumor-specific adaptive immune response is also dependent on DC interactions with other innate cell effectors, such as natural killer cells. The different modalities by which DCs can acquire tumor antigens also significantly affect antigen presentation because, in addition to the presentation of tumor antigens on MHC class II upon the classical exogenous antigen processing pathway, DCs are equipped to directly activate cytotoxic T cells via both cross-priming and cross-dressing. Here, the different forms of tumor antigen presentation by DCs are reviewed and discussed. We also discuss the ways in which this novel information could be exploited in the design of DC-based cancer vaccines. PMID- 26853849 TI - Role of Inflammation Amplifier-Induced Growth Factor Expression in the Development of Inflammatory Diseases. AB - Inflammation is a fundamental response induced by the immune system to protect the body against pathogens, tissue damage, and stress. At the same time, recent studies have suggested that chronically induced inflammation is involved in various human diseases and disorders. Thus, understanding the molecular mechanisms of chronic inflammation could provide therapeutic value. Many mediators such as cytokines or chemokines regulate inflammatory responses. Among them, interleukin(IL)-6 is a prominent cytokine that induces and maintains inflammatory reactions. It is expressed by activated CD4+ T cells and also non immune cells such as fibroblasts and epithelial cells. We discovered an inflammation-induction machinery, the inflammation amplifier, which is activated by the simultaneous stimulation of nuclear factor-kappa B (NF-kappaB) and signal transducers and activator of transcription 3 (STAT3) via various cytokines like IL-17 and IL-6 in non-immune cells. Activation of the inflammation amplifier induces a synergistic increase of IL-6, inflammatory chemokines, and growth factors. Using genome-wide screening, we identified several growth factors as mediators of the inflammation amplifier. In this review, we highlight the role of growth factors in the inflammation mechanism with special attention on the inflammation amplifier. PMID- 26853852 TI - Role of CD38 Expression in Diagnosis and Pathogenesis of Chronic Lymphocytic Leukemia and Its Potential as Therapeutic Target. AB - CD38 is widely accepted as a marker for unfavorable prognosis in chronic lymphocytic leukemia (CLL). Nevertheless, its direct contribution to the disease pathogenesis is not very well understood. Recent data indicate that CD38 may promote CLL pathogenesis by enhancing proliferation in synergy with B-cell receptor (BCR) signaling and by supporting migration and homing of CLL cells to secondary lymphoid organs, where the malignant cells receive support from the tumor microenvironment. CD38 may also contribute to a suppressed anticancer immune response through the production of tolerogenic compounds. This review first shortly summarizes the biology, expression, and function of CD38 in general and in CLL cells in more detail. Next, the current literature and open questions regarding a direct contribution of CD38 to CLL pathogenesis are critically reviewed. Finally, I discuss the potential of CD38 as therapeutic target in light of its possible roles in CLL and the promising results of clinical trials with CD38 antibodies in multiple myeloma (MM). PMID- 26853853 TI - An Electrochemical Sensing Platform Based on Liquid-Liquid Microinterface Arrays Formed in Laser-Ablated Glass Membranes. AB - Arrays of microscale interfaces between two immiscible electrolyte solutions (MUITIES) were formed using glass membranes perforated with microscale pores by laser ablation. Square arrays of 100 micropores in 130 MUm thick borosilicate glass coverslips were functionalized with trichloro(1H,1H,2H,2H perfluorooctyl)silane on one side, to render the surface hydrophobic and support the formation of aqueous-organic liquid-liquid microinterfaces. The pores show a conical shape, with larger radii at the laser entry side (26.5 MUm) than at the laser exit side (11.5 MUm). The modified surfaces were characterized by contact angle measurements and X-ray photoelectron spectroscopy. The organic phase was placed on the hydrophobic side of the membrane, enabling the array of MUITIES to be located at either the wider or narrower pore mouth. The electrochemical behavior of the MUITIES arrays were investigated by tetrapropylammonium ion transfer across water-1,6-dichlorohexane interfaces together with finite element computational simulations. The data suggest that the smallest microinterfaces (formed on the laser exit side) were located at the mouth of the pore in hemispherical geometry, while the larger microinterfaces (formed on the laser entry side) were flatter in shape but exhibited more instability due to the significant roughness of the glass around the pore mouths. The glass membrane supported MUITIES arrays presented here provide a new platform for chemical and biochemical sensing systems. PMID- 26853851 TI - The p53 Transcriptional Network Influences Microglia Behavior and Neuroinflammation. AB - The tumor-suppressor protein p53 belongs to a family of proteins that play pivotal roles in multiple cellular functions including cell proliferation, cell death, genome stability, and regulation of inflammation. Neuroinflammation is a common feature of central nervous system (CNS) pathology, and microglia are the specialized resident population of CNS myeloid cells that initiate innate immune responses. Microglia maintain CNS homeostasis through pathogen containment, phagocytosis of debris, and initiation of tissue-repair cascades. However, an unregulated pro-inflammatory response can lead to tissue injury and dysfunction in both acute and chronic inflammatory states. Therefore, regulation of the molecular signals that control the induction, magnitude, and resolution of inflammation are necessary for optimal CNS health. We and others have described a novel mechanism by which p53 transcriptional activity modulates microglia behaviors in vitro and in vivo. Activation of p53 induces expression of microRNAs (miRNAs) that support microglia pro-inflammatory functions and suppress anti inflammatory and tissue repair behaviors. In this review, we introduce the previously described roles of the p53 signaling network and discuss novel functions of p53 in the microglia-mediated inflammatory response in CNS health and disease. Ultimately, improved understanding of the molecular regulators modulated by p53 transcriptional activity in microglia will enhance the development of rational therapeutic strategies to harness the homeostatic and tissue repair functions of microglia. PMID- 26853854 TI - Kinetics of the ClO + HO2 reaction over the temperature range T = 210-298 K. AB - The rate coefficient for the atmospherically important radical reaction: which leads to ozone depletion, has been studied over the temperature range T = 210-298 K and at ambient pressure p = 760 +/- 20 Torr. The reaction was studied using laser flash photolysis radical generation coupled with broadband charge coupled device absorption spectroscopy employing a two-dimensional charge-coupled-device (CCD) detection system. ClO radicals were generated following the photolysis of Cl2 and Cl2O gas mixtures diluted in nitrogen and oxygen. ClO radicals were monitored using broadband fingerprinting of their characteristic vibronic (A(2)Pi <- X(2)Pi) spectral structure, representing a definitive monitoring of this radical. Addition of hydroperoxy radical precursors to the gas mixture (methanol and oxygen) subsequently led to a competition for photolytically generated Cl atoms and a simultaneous prompt formation of both ClO and HO2 radicals. Detailed analysis and modelling of the radical production routes provided a degree of constraint into numerical integration simulations which were then used to interrogate and fit to ClO temporal profiles to extract the rate coefficient k1. The ambient temperature (T = 298 K) rate coefficient reported is k1 = (8.5 +/- 1.5) * 10(-12) cm(3) molecule(-1) s(-1). The rate coefficient, k1, is described by the Arrhenius expression:where errors are 1sigma statistical only. This significant rate coefficient is greater than previously reported, with a stronger negative temperature dependence than previously observed. Consequently this suggests that the contribution of to ozone loss, in particular at mid-latitudes might be currently underestimated in models. This work reports atmospheric pressure kinetic parameters for this reaction which are greater than those reported from low pressure studies, perhaps supporting ClO and HO2 association as predicted by previous theoretical studies of this process and highlighting the need for further pressure dependent experimental studies of the title reaction, which has been demonstrated here to be effective as an ozone loss process over a wide temperature range. PMID- 26853855 TI - Glutamine for induction of remission in Crohn's disease. AB - BACKGROUND: Crohn's disease is a chronic relapsing condition of the alimentary tract with a high morbidity secondary to bowel inflammation. Glutamine plays a key role in maintaining the integrity of the intestinal mucosa and has been shown to reduce inflammation and disease activity in experimental models of Crohn's disease. OBJECTIVES: To evaluate the efficacy and safety of glutamine supplementation for induction of remission in Crohn's disease. SEARCH METHODS: We searched the following databases from inception to November 15, 2015: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and the Cochrane IBD Group Specialised Register. Study references were also searched for additional trials. There were no language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) that compared glutamine supplementation administered by any route to a placebo, active comparator or no intervention in people with active Crohn's disease were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed the methodological quality of the included studies. The Cochrane risk of bias tool was used to assess methodological quality. The primary outcome measure was clinical or endoscopic remission. Secondary outcomes included intestinal permeability, clinical response, quality of life, growth in children and adverse events. Risk ratios and 95% confidence intervals were calculated for dichotomous outcomes. The overall quality of the evidence supporting the primary outcome was evaluated using the GRADE criteria. MAIN RESULTS: Two small RCTs (total 42 patients) met the inclusion criteria and were included in the review. One study (18 patients) compared four weeks of treatment with a glutamine-enriched polymeric diet (42% amino acid composition) to a standard polymeric diet (4% amino acid composition) with low glutamine content in paediatric patients (< 18 years of age) with active Crohn's disease. The other study (24 patients) compared glutamine-supplemented total parenteral nutrition to non-supplemented total parenteral nutrition in adult patients (> 18 years of age) with acute exacerbation of inflammatory bowel disease. The paediatric study was rated as low risk of bias. The study in adult patients was rated as unclear risk of bias for blinding and low risk of bias for all other items. It was not possible to pool data for meta-analysis because of significant differences in study populations, nature of interventions, and the way outcomes were assessed. Data from one study showed no statistically significant difference in clinical remission rates at four weeks. Forty-four per cent (4/9) of patients who received a glutamine enriched polymeric diet achieved remission compared to 56% (5/9) of patients who received a standard low-glutamine polymeric diet (RR 0.80, 95% CI 0.31 to 2.04). A GRADE analysis indicated that the overall quality of evidence for this outcome was low due to serious imprecision (9 events). In both included studies, no statistically significant changes in intestinal permeability were found between patients who received glutamine supplementation and those who did not. Neither study reported on clinical response, quality of life or growth in children. Adverse event data were not well documented. There were no serious adverse events in the paediatric study. The study in adult patients reported three central catheter infections with positive blood cultures in the glutamine group compared to none in the control group (RR 7.00, 95% CI 0.40 to 122.44). AUTHORS' CONCLUSIONS: Currently there is insufficient evidence to allow firm conclusions regarding the efficacy and safety of glutamine for induction of remission in Crohn's disease. Data from two small studies suggest that glutamine supplementation may not be beneficial in active Crohn's disease but these results need to be interpreted with caution as they are based on small numbers of patients. This review highlights the need for adequately powered randomised controlled trials to investigate the efficacy and safety of glutamine for induction of remission in Crohn's disease. PMID- 26853850 TI - Regulatory Roles of Rpl22 in Hematopoiesis: An Old Dog with New Tricks. AB - Ribosomal proteins have long been known to serve critical roles in facilitating the biogenesis of the ribosome and its ability to synthesize proteins. However, evidence is emerging that suggests ribosomal proteins are also capable of performing tissue-restricted, regulatory functions that impact normal development and pathological conditions, including cancer. The challenge in studying such regulatory functions is that elimination of many ribosomal proteins also disrupts ribosome biogenesis and/or function. Thus, it is difficult to determine whether developmental abnormalities resulting from ablation of a ribosomal protein result from loss of core ribosome functions or from loss of the regulatory function of the ribosomal protein. Rpl22, a ribosomal protein component of the large 60S subunit, provides insight into this conundrum; Rpl22 is dispensable for both ribosome biogenesis and protein synthesis yet its ablation causes tissue restricted disruptions in development. Here we review evidence supporting the regulatory functions of Rpl22 and other ribosomal proteins. PMID- 26853857 TI - Early and intermediate-term results of the extracardiac conduit total cavopulmonary connection for functional single-ventricle hearts. AB - BACKGROUND/PURPOSE: Fontan operation has evolved from atriopulmonary connection to total cavopulmonary connection (TCPC) due to its advantages in terms of hemodynamics and reduction of atrium-related complications. We analyzed the early and intermediate-term results of extracardiac conduit TCPC (EC-TCPC) procedure in patients with functional single ventricle to investigate the risk factors of surgical mortality and intermediate failure. METHODS: Retrospective review of the medical records of 88 consecutive patients with functional single ventricle who underwent EC-TCPC from 2000 to 2013 was conducted. RESULTS: The follow-up was 100% complete, ranging from 3 months to 13 years (mean 7.0 +/- 3.8 years). There were two (2.3%) hospital and 18 (20.4%) late deaths. The estimated event-free survival rates at 1 year, 5 years, and 10 years were 90.6%, 89.3%, and 77.2%, respectively. On univariate analysis, fenestration was the only risk factor for surgical mortality (p = 0.027). On multivariate analysis, the significant atrioventricular valve regurgitation was the only risk factor for intermediate failure (p = 0.017). CONCLUSION: The clinical results of EC-TCPC in patients with functional single ventricle were satisfactory. The patients who needed fenestration during operation had higher risk of surgical mortality. Significant atrioventricular valve regurgitation had negative impact on intermediate survival. PMID- 26853856 TI - Naive Human Pluripotent Cells Feature a Methylation Landscape Devoid of Blastocyst or Germline Memory. AB - Human embryonic stem cells (hESCs) typically exhibit "primed" pluripotency, analogous to stem cells derived from the mouse post-implantation epiblast. This has led to a search for growth conditions that support self-renewal of hESCs akin to hypomethylated naive epiblast cells in human pre-implantation embryos. We have discovered that reverting primed hESCs to a hypomethylated naive state or deriving a new hESC line under naive conditions results in the establishment of Stage Specific Embryonic Antigen 4 (SSEA4)-negative hESC lines with a transcriptional program resembling the human pre-implantation epiblast. In contrast, we discovered that the methylome of naive hESCs in vitro is distinct from that of the human epiblast in vivo with loss of DNA methylation at primary imprints and a lost "memory" of the methylation state of the human oocyte. This failure to recover the naive epiblast methylation landscape appears to be a consistent feature of self-renewing hypomethylated naive hESCs in vitro. PMID- 26853858 TI - Outstanding drug loading capacity by water stable microporous MOF: a potential drug carrier. AB - A robust, highly water stable (up to 3 weeks), microporous MOF, [Zn8(O)2(CDDB)6(DMF)4(H2O)] {where CDDB = 4,4'-(9-H carbazole-3,6-diyl)dibenzoic acid}, was synthesized based on an open N-H site by a solvothermal process and exhibited an outstanding loading capacity (around 53.3 wt%) and satisfactory release capability (64.9% and 81.9%) for 5-fluorouracil, constituting a negligible cytotoxicity effect. PMID- 26853859 TI - A self-assembling beta-peptide hydrogel for neural tissue engineering. AB - We report a new class of beta-peptide based hydrogel for neural tissue engineering. Our beta-peptide forms a network of nanofibres in aqueous solution, resulting in a stable hydrogel at physiological conditions. The hydrogel shows excellent compatibility with neural cells and provides a suitable environment for cells to adhere and proliferate. PMID- 26853860 TI - Predicting the outcome for individual patients with traumatic brain injury: a case-based review. AB - BACKGROUND: Traumatic brain injuries result in significant morbidity and mortality. Accurate prediction of prognosis is desirable to inform treatment decisions and counsel family members. Objective To review the currently available prognostic tools for use in traumatic brain injury (TBI), to analyse their value in individual patient management and to appraise ongoing research on prognostic modelling. METHODS AND RESULTS: We present two patients who sustained a TBI in 2011-2012 and evaluate whether prognostic models could accurately predict their outcome. The methodology and validity of current prognostic models are analysed and current research that might contribute to improved individual patient prognostication is evaluated. CONCLUSION: Predicting prognosis in the acute phase after TBI is complex and existing prognostic models are not suitable for use at the individual patient level. Data derived from these models should only be used as an adjunct to clinical judgement and should not be used to set limits for acute care interventions. Information from neuroimaging, physiological monitoring and analysis of biomarkers or genetic polymorphisms may be used in the future to improve accuracy of individual patient prognostication. Clinicians should consider offering full supportive treatment to patients in the early phase after injury whilst the outcome is unclear. PMID- 26853862 TI - Launch of Zoological Letters. AB - A new open-access journal, Zoological Letters, was launched as a sister journal to Zoological Science, in January 2015. The new journal aims at publishing topical papers of high quality from a wide range of basic zoological research fields. This review highlights the notable reviews and research articles that have been published in the first year of Zoological Letters, providing an overview on the current achievements and future directions of the journal. PMID- 26853863 TI - Habituation of Backward Escape Swimming in the Marbled Crayfish. AB - In the present study, we performed behavioral analyses of the habituation of backward escape swimming in the marbled crayfish, Procambarus fallax. Application of rapid mechanical stimulation to the rostrum elicited backward swimming following rapid abdominal flexion of crayfish. Response latency was very short tens of msec-suggesting that backward swimming is mediated by MG neurons. When stimulation was repeated with 10 sec interstimulus intervals the MG-like tailflip did not occur, as the animals showed habituation. Retention of habituation was rather short, with most animals recovering from habituation within 10 min. Previous experience of habituation was remembered and animals habituated faster during a second series of experiments with similar repetitive stimuli. About half the number of stimulus trials was necessary to habituate in the second test compared to the first test. This promotion of habituation was observed in animals with delay periods of rest within 60 min following the first habituation. After 90 min of rest from the first habitation, animals showed a similar time course for the second habituation. With five stimuli at 15 min interval during 90 min of the rest, trained animals showed rapid habituation, indicating reinforcement of the memory of previous experiments. Crayfish also showed dishabituation when mechanical stimulation was applied to the tail following habituation. PMID- 26853861 TI - Interstitial fluid pressure regulates collective invasion in engineered human breast tumors via Snail, vimentin, and E-cadherin. AB - Many solid tumors exhibit elevated interstitial fluid pressure (IFP). This elevated pressure within the core of the tumor results in outward flow of interstitial fluid to the tumor periphery. We previously found that the directionality of IFP gradients modulates collective invasion from the surface of patterned three-dimensional (3D) aggregates of MDA-MB-231 human breast cancer cells. Here, we used this 3D engineered tumor model to investigate the molecular mechanisms underlying IFP-induced changes in invasive phenotype. We found that IFP alters the expression of genes associated with epithelial-mesenchymal transition (EMT). Specifically, the levels of Snail, vimentin, and E-cadherin were increased under pressure conditions that promoted collective invasion. These changes in gene expression were sufficient to direct collective invasion in response to IFP. Furthermore, we found that IFP modulates the motility and persistence of individual cells within the aggregates, which are also influenced by the expression levels of EMT markers. Together, these data provide insight into the molecular mechanisms that guide collective invasion from primary tumors in response to IFP. PMID- 26853864 TI - A Single-Wing Removal Method to Assess Correspondence Between Gene Expression and Phenotype in Butterflies: The Case of Distal-less. AB - It is often desirable but difficult to retrieve information on the mature phenotype of an immature tissue sample that has been subjected to gene expression analysis. This problem cannot be ignored when individual variation within a species is large. To circumvent this problem in the butterfly wing system, we developed a new surgical method for removing a single forewing from a pupa using Junonia orithya; the operated pupa was left to develop to an adult without eclosion. The removed right forewing was subjected to gene expression analysis, whereas the non-removed left forewing was examined for color patterns. As a test case, we focused on Distal-less (Dll), which likely plays an active role in inducing elemental patterns, including eyespots. The Dll expression level in forewings was paired with eyespot size data from the same individual. One third of the operated pupae survived and developed wing color patterns. Dll expression levels were significantly higher in males than in females, although male eyespots were smaller in size than female eyespots. Eyespot size data showed weak but significant correlations with the Dll expression level in females. These results demonstrate that a single-wing removal method was successfully applied to the butterfly wing system and suggest the weak and non-exclusive contribution of Dll to eyespot size determination in this butterfly. Our novel methodology for establishing correspondence between gene expression and phenotype can be applied to other candidate genes for color pattern development in butterflies. Conceptually similar methods may also be applicable in other developmental systems. PMID- 26853865 TI - Expression of Two Classes of Pax6 Transcripts in Reprogramming Retinal Pigment Epithelium Cells of the Adult Newt. AB - The adult newt has the remarkable ability to regenerate a functional retina from retinal pigment epithelium (RPE) cells, even when the neural retina (NR) is completely lost from the eye. In this system, RPE cells are reprogrammed into a unique state of multipotent cells, named RPESCs, in an early phase of retinal regeneration. However, the signals that trigger reprogramming remain unknown. Here, to approach this issue we focused on Pax6, a transcription factor known to be expressed in RPESCs. We first identified four classes (v1, v2, v3 and v4) of Pax6 variants in the eye of adult newt, Cynops pyrrhogaster. These variants were expressed in most tissues of the intact eye in different combinations but not in the RPE, choroid or sclera. On the basis of this information, we investigated the expression of Pax6 in RPE cells after the NR was removed from the eye by surgery (retinectomy), and found that two classes (v1 and v2) of Pax6 variants were newly expressed in RPE cells 10 days after retinectomy, both in vivo and in vitro (RLEC system). In the RLEC system, we found that Pax6 expression is mediated through a pathway separate from the MEK-ERK pathway, which is required for cell cycle re entry of RPE cells. These results predict the existence of a pathway that may be of fundamental importance to a better understanding of the reprogramming of RPE cells in vivo. PMID- 26853866 TI - Comparative Developmental Staging of Female and Male Water Fleas Daphnia pulex and Daphnia magna During Embryogenesis. AB - The freshwater crustacean genus Daphnia has been used extensively in ecological, developmental and ecotoxicological studies. Daphnids produce only female offspring by parthenogenesis under favorable conditions, but in response to various unfavorable conditions and external stimuli, they produce male offspring. Although we reported that exogenous exposure to juvenile hormones and their analogs can induce male offspring even under female-producing conditions, we recently established a male induction system in the Daphnia pulex WTN6 strain simply by changing day-length. This male and female induction system is suitable for understanding the innate mechanisms of sexual dimorphic development in daphnids. Embryogenesis has been described as a normal plate (developmental staging) in various daphnid species; however, all studies have mainly focused on female development. Here, we describe the developmental staging of both sexes during embryogenesis in two representative daphnids, D. pulex and D. magna, based on microscopic time-course observations. Our findings provide the first detailed insights into male embryogenesis in both species, and contribute to the elucidation of the mechanisms underlying sexual differentiation in daphnids. PMID- 26853867 TI - Multiple Origins and Admixture of Recently Expanding Japanese Wild Boar (Sus scrofa leucomystax) Populations in Toyama Prefecture of Japan. AB - Japanese wild boar (Sus scrofa leucomystax) populations have expanded drastically throughout the Japanese Archipelago in recent decades. To elucidate the dispersal patterns of Japanese wild boar in Toyama Prefecture in central Japan, we used a multi-locus microsatellite DNA analysis to determine its population structure and the degree of admixture. The deviation from Hardy-Weinberg equilibrium was detected in either total or separate regional wild boar samples from Toyama Prefecture. This result could be explained by the Wahlund effect resulting from the mixture of samples from different sources. Bayesian structure analysis, assignment test, and factorial correspondence analysis suggested that wild boars around Toyama Prefecture derive from at least two ancestral sources. The migration and possible mating of each individual may have occurred recently and continued in each geographically neighboring region. The present genetic results may be useful for prediction of future dispersal patterns of Japanese wild boar, as well as other animals in expansion. PMID- 26853869 TI - Tidal-Flat Macrobenthos as Diets of the Japanese Eel Anguilla japonica in Western Japan, with a Note on the Occurrence of a Parasitic Nematode Heliconema anguillae in Eel Stomachs. AB - Dietary items of the Japanese eel Anguilla japonica inhabiting estuaries were examined by analyses of the gut (stomach and intestine) contents in two areas in Kyushu, western Japan. In a small estuary in Kagoshima Bay, where seven eel guts were examined, almost all of the dietary organisms consisted of Hemigrapsus crabs and Hediste polychaetes, both of which commonly occurred on tidal flats of this site during our survey on the macrobenthic fauna. In another large estuary in the innermost part of the Ariake Sea, where 14 eel guts were examined, 11 macrobenthic species (nine crustaceans, a polychaete, and a gastropod) were found in the gut contents, mostly consisting of mudflat-specific species. The dietary items are almost completely different not only between the two estuaries, but also among three neighboring sites within the large estuary in the Ariake Sea. These results show that Japanese eels feed on various macrobenthic invertebrates inhabiting estuarine tidal flats at each site. The variety of the prey species occupying different habitats indicates that their foraging areas extend to a wide range of estuarine tidal flats from the upper to lower littoral zones. The physalopterid nematode Heliconema anguillae was found parasitic in eel stomachs in both estuaries. The prevalence of the nematode was higher in the estuary in Kagoshima Bay (100%) than that in the Ariake Sea (43%), although the intensity in the former (4-94 nematodes per infected stomach) was comparable to that of the latter (2-96). The relationship between the nematode infection and the dietary items of Japanese eels is discussed. PMID- 26853868 TI - Japanese Wolves are Genetically Divided into Two Groups Based on an 8-Nucleotide Insertion/Deletion within the mtDNA Control Region. AB - The mitochondrial DNA (mtDNA) control region (198- to 598-bp) of four ancient Canis specimens (two Canis mandibles, a cranium, and a first phalanx) was examined, and each specimen was genetically identified as Japanese wolf. Two unique nucleotide substitutions, the 78-C insertion and the 482-G deletion, both of which are specific for Japanese wolf, were observed in each sample. Based on the mtDNA sequences analyzed, these four specimens and 10 additional Japanese wolf samples could be classified into two groups- Group A (10 samples) and Group B (4 samples)-which contain or lack an 8-bp insertion/deletion (indel), respectively. Interestingly, three dogs (Akita-b, Kishu 25, and S-husky 102) that each contained Japanese wolf-specific features were also classified into Group A or B based on the 8-bp indel. To determine the origin or ancestor of the Japanese wolf, mtDNA control regions of ancient continental Canis specimens were examined; 84 specimens were from Russia, and 29 were from China. However, none of these 113 specimens contained Japanese wolf-specific sequences. Moreover, none of 426 Japanese modern hunting dogs examined contained these Japanese wolf-specific mtDNA sequences. The mtDNA control region sequences of Groups A and B appeared to be unique to grey wolf and dog populations. PMID- 26853870 TI - Migration of Tundra Swans (Cygnus columbianus) Wintering in Japan Using Satellite Tracking: Identification of the Eastern Palearctic Flyway. AB - Migration through the Eastern Palearctic (EP) flyway by tundra swans (Cygnus columbianus) has not been thoroughly documented. We satellite-tracked the migration of 16 tundra swans that winter in Japan. The objectives of this study were 1) to show the migration pattern of the EP flyway of tundra swans; 2) to compare this pattern with the migration pattern of whooper swans; and 3) to identify stopover sites that are important for these swans' conservation. Tundra swans were captured at Kutcharo Lake, Hokkaido, in 2009-2012 and satellite tracked. A new method called the "MATCHED (Migratory Analytical Time Change Easy Detection) method" was developed. Based on median, the spring migration began on 18 April and ended on 27 May. Autumn migration began on 9 September and ended on 2 November. The median duration of the spring and autumn migrations were 48 and 50 days, respectively. The mean duration at one stopover site was 5.5 days and 6.8 days for the spring and autumn migrations, respectively. The number of stopover sites was 3.0 and 2.5 for the spring and autumn migrations, respectively. The mean travel distances for the spring and autumn migrations were 6471 and 6331 km, respectively. Seven migration routes passing Sakhalin, the Amur River, and/or Kamchatka were identified. There were 15, 32, and eight wintering, stopover, and breeding sites, respectively. The migration routes and staging areas of tundra swans partially overlap with those of whooper swans, whose migration patterns have been previously documented. The migration patterns of these two swan species that winter in Japan confirm the importance of the Amur River, Udyl' Lake, Shchastya Bay, Aniva Bay, zaliv Chayvo Lake, zal Piltun Lake, zaliv Baykal Lake, Kolyma River, Buyunda River, Sen-kyuyel' Lake, and northern coastal areas of the Sea of Okhotsk. PMID- 26853871 TI - Whole Genome Re-Sequencing of Three Domesticated Chicken Breeds. AB - Chicken is one of the most popular domesticated species worldwide, as it can serve an important role in agricultural as well as biomedical research fields. Because it inhabits almost every continent and presents diverse morphology and traits, the need of genetic markers for distinguishing each breed for various purposes has increased. The whole genome sequencing of three different breeds (White Leghorn, Korean domestic, and Araucana) that show similar coloring patterns, with the exception of the White Leghorn breed, have confirmed previously reported genomic alterations and identified many novel variants. Additionally, the Whole Genome Re-Sequencing (WGRS) approach identified an approximately 4 kb insert within SLCO1B3 responsible for blue egg shell color. Targeted investigation of pigment-related genes corroborated previously reported non-synonymous mutations, and provided deeper insight into chicken coloring, where not a single but a combination of non-synonymous mutations in the MC1R gene is likely to be responsible for altered feather coloring. PMID- 26853872 TI - Olfactory Memory Storage and/or Retrieval Requires the Presence of the Exact Tentacle Used During Memory Acquisition in the Terrestrial Slug Limax. AB - Terrestrial pulmonates can form odor-aversion memories once a food odor is presented in combination with an aversive stimulus. Most of the olfactory information ascends via a tentacular ganglion located in the tip of the two pairs of tentacles, and is then transmitted to the higher olfactory center, the procerebrum. The procerebrum is the locus of memory storage and has been shown to be necessary for odor-aversion learning. However, it is unknown whether the procerebrum is the sole locus in which the memory engram resides. By exploiting the regenerative ability of tentacles, here we investigated whether tentacles function merely in transmitting olfactory information to the procerebrum, or constitute a part of the memory engram. We showed that after removal of the tentacles used during memory acquisition, slugs were unable to retrieve the memory, even if these tentacles were regenerated sufficiently to subserve memory function. Our results support the view that tentacles are more than conduits of odor information; they also participate in the formation of the memory engram. PMID- 26853873 TI - Lowering Temperature is the Trigger for Glycogen Build-Up and Winter Fasting in Crucian Carp (Carassius carassius). AB - Seasonal changes in physiology of vertebrate animals are triggered by environmental cues including temperature, day-length and oxygen availability. Crucian carp (Carassius carassius) tolerate prolonged anoxia in winter by using several physiological adaptations that are seasonally activated. This study examines which environmental cues are required to trigger physiological adjustments for winter dormancy in crucian carp. To this end, crucian carp were exposed to changing environmental factors under laboratory conditions: effects of declining water temperature, shortening day-length and reduced oxygen availability, separately and in different combinations, were examined on glycogen content and enzyme activities involved in feeding (alkaline phosphatase, AP) and glycogen metabolism (glycogen synthase, GyS; glycogen phosphorylase, GP). Lowering temperature induced a fall in activity of AP and a rise in glycogen content and rate of glycogen synthesis. Relative mass of the liver, and glycogen concentration of liver, muscle and brain increased with lowering temperature. Similarly activity of GyS in muscle and expression of GyS transcripts in brain were up-regulated by lowering temperature. Shortened day-length and oxygen availability had practically no effects on measured variables. We conclude that lowering temperature is the main trigger in preparation for winter anoxia in crucian carp. PMID- 26853874 TI - Identification and Expression Profiles of microRNA in Dolphin. AB - Recently, microRNAs (miRNAs) are focused on the role of biomarker because they are stable in serum and plasma, and some of them express in the specific organs and increase with the organ injury. Thus miRNAs may be very useful as biomarkers for monitoring the health and condition of dolphins and for detecting disorders in aquariums. Here, a small RNA library was made from dolphin lung, liver and spleen, and miRNA expression patterns were then determined for 15 different tissues. We identified 62 conserved miRNA homologs in the dolphin small RNA library and found high expression miRNAs in specific tissues: miR-125b and miR 221 were highly expressed in brain, miR-23b in heart, miR-199a and miR-223 in lung, and miR-122-5p in liver. Some of these tissue-enriched miRNAs may be useful as specific and sensitive diagnostic blood biomarkers for organ injury in dolphins. PMID- 26853875 TI - Expression of Membrane Progestin Receptors (mPRs) in Granulosa Cells of Medaka Preovulatory Follicles. AB - Membrane progestin receptor (mPR) alpha on the cell membrane of the oocyte is involved in the meiotic maturation of vertebrates, including teleosts, but little is known about the role of this membrane-bound follicular receptor. We investigated the ovarian expression of membrane progestin receptor (mPR) mRNA in medaka. In follicles that were destined to ovulate, transcripts of mPRalpha and mPRgamma were expressed in the oocytes as well as the granulosa cells. Transcripts of mPRalpha and mPRgamma were expressed at relatively constant levels in the whole ovary and in the preovulatory follicles throughout the 24-h spawning cycle. In vitro incubation of the preovulatory follicles with recombinant medaka luteinizing hormone caused no significant changes in the expression of mPRalpha and mPRgamma mRNA, suggesting LH-independent follicular expression of these mPR genes. Using HEK293T cells expressing medaka mPRs, forskolin-elevated intracellular cAMP levels were found to be reduced on treatment of the cells with ligand 17alpha, 20beta-dihydroxy-4-pregnen-3-one (DHP), but only in the cells expressing mPRalpha. These results indicate that activation of mPRalpha and mPRgamma with DHP may cause differential effects on the granulosa cells. Information obtained from the present study may help to elucidate the role of mPRalpha and mPRgamma in the granulosa cells of the follicles. PMID- 26853876 TI - Identification and Expression Analysis of Upregulated Genes in the Resting Egg Producing Water Flea (Daphnia pulex). AB - Water fleas (Daphnia pulex) normally produce subitaneous eggs that initiate development immediately after oviposition. However, in response to habitat degradation, resting eggs are produced, which are enclosed in a sturdy outer envelope (ephippium) and can survive in harsh environments for an extended time. To understand the molecular mechanism underlying resting egg production in D. pulex, we investigated the genes whose expression patterns played a role in the production and identified the following six candidate genes: Dpfa-1, Dpfa-2, Dpep 1, Dpep-2, Dpep-3, and Dpep-4. These six genes displayed > 40-fold higher expression levels in resting egg-producing animals compared with those in subitaneous egg-producing animals at the period when the ovaries were mature. Dpfa-1 and Dpfa-2 were expressed in the fat cells, and their expression patterns were synchronized with the development of resting egg oocytes in the ovary. In contrast, Dpep-1-4 were expressed in the morphologically altered epidermal cells of the brood chamber with the formation of the ephippium, and their expression patterns were also related to ephippium formation. Our results suggest that the former two genes encode the resting egg-specific components produced by fat cells and that the latter four genes encode the components related to the ephippium formation synthesized by epidermal cells. PMID- 26853877 TI - Restructuring the Traditional Suborders in the Order Scleractinia Based on Embryogenetic Morphological Characteristics. AB - The order Scleractinia includes two distinct groups, which are termed "complex" and "robust" as indicated by the molecular phylogeny of mitochondrial 16S ribosomal gene sequences. Since this discovery, coral taxonomists have been seeking morphological characters for grouping this deep division in the order Scleractinia. Recently, morphological characteristics during embryogenesis that facilitate grouping the two clades as "complex" and "robust" were reported, thus clarifying a deep division in the Scleractinia. In the present report, I establish two new suborders, Refertina and Vacatina, on the basis of the embryogenetic morphological characteristics, molecular data, and new observations of Tubastraea coccinea and Cyphastrea serailia embryogenesis. In particular, the embryo of T. coccinea has a possible fertilization membrane that was first observed in the phylum Cnidaria. The new suborder Refertina consists of the families that belong to the "complex" clade and have no or little blastocoel. The new suborder Vacatina is composed of the families that fall into the "robust" clade and have an apparent blastocoel. PMID- 26853878 TI - Vertebrate Neural Stem Cells: Development, Plasticity, and Regeneration. AB - Natural recovery from disease and damage in the adult mammalian central nervous system (CNS) is limited compared with that in lower vertebrate species, including fish and salamanders. Species-specific differences in the plasticity of the CNS reflect these differences in regenerative capacity. Despite numerous extensive studies in the field of CNS regeneration, our understanding of the molecular mechanisms determining the regenerative capacity of the CNS is still relatively poor. The discovery of adult neural stem cells (aNSCs) in mammals, including humans, in the early 1990s has opened up new possibilities for the treatment of CNS disorders via self-regeneration through the mobilization of these cells. However, we now know that aNSCs in mammals are not plastic enough to induce significant regeneration. In contrast, aNSCs in some regenerative species have been found to be as highly plastic as early embryonic neural stem cells (NSCs). We must expand our knowledge of NSCs and of regenerative processes in lower vertebrates in an effort to develop effective regenerative treatments for damaged CNS in humans. PMID- 26853879 TI - Vitamin D Deficiency with High Intact PTH Levels is More Common in Younger than in Older Women: A Study of Women Aged 39-64 Years. AB - Low serum 25-hydroxyvitamin D (25(OH)D) levels are implicated as a risk factor for hip and spine fractures. Studies of the relation between 25(OH)D levels and fractures have primarily involved elderly osteoporosis patients or patients with fractures; however, the serum 25(OH)D and parathyroid hormone (PTH) status in younger adult populations remains largely unknown. We evaluated serum 25(OH)D and intact PTH levels in 411 women aged 39-64 years who were not receiving medication for osteoporosis or other bone diseases. Serum 25(OH)D levels were positively correlated with age (P = 0.019), whereas intact PTH levels were inversely correlated with 25(OH)D levels (P < 0.001). Thus, low vitamin D levels with high intact PTH levels were more common in younger than in older women. Our data show that serum 25(OH)D insufficiency could be a more serious concern in the younger population than had been previously anticipated. Because serum 25(OH)D insufficiency is reportedly a risk factor for hip and spine fracture, the number of fracture patients could increase in the future, suggesting that we may need to correct the serum vitamin D/intact PTH status to prevent future osteoporosis. PMID- 26853881 TI - Extraordinary optical transmission in nanopatterned ultrathin metal films without holes. AB - We experimentally and theoretically demonstrate that a continuous gold film on a periodically textured substrate exhibits extraordinary optical transmission, even though no holes were etched in the film. Our film synthesis started by nanoimprinting a periodic array of nanocups with a period of ~750 nm on a polystyrene film over a glass substrate. A thin non-conformal gold film was sputter-deposited on the polystyrene by angle-directed deposition. The gold film was continuous with spatial thickness variation, the film being thinnest at the bottom of the nanocup. Measurements revealed an extraordinary transmission peak at a wavelength just smaller than the period, with an enhancement of ~2.5 compared to the classically expected value. Scattering matrix simulations model well the transmission and reflectance measurements when an ultrathin gold layer (~5 nm), smaller than the skin depth is retained at the bottom of the nanocups. Electric field intensities are enhanced by >100 within the nanocup, and ~40 in the ultrathin gold layer causing transmission through it. We show a wavelength red-shift of ~30 nm in the extraordinary transmission peak when the nanocups are coated with a thin film of a few nanometers, which can be utilized for biosensing. The continuous corrugated metal films are far simpler structures to observe extraordinary transmission, circumventing the difficult process of etching the metal film. Such continuous metal films with ultrathin regions are simple platforms for non-linear optics, plasmonics, and biological and chemical sensing. PMID- 26853880 TI - Epigenetic suppression of iNOS expression in human endothelial cells: A potential role of Ezh2-mediated H3K27me3. AB - OBJECTIVE: Cytokines strongly induce expression of the inducible nitric oxide synthase (iNOS) in rodent but not in human endothelial cells. We recently identified NOS2 as a potential target of the histone methyltransferase enhancer of zeste homolog 2 which mediates trimethylation of histone 3 at lysine 27 (H3K27me3). METHODS AND RESULTS: Compared to an unspecific IgG control, chromatin immunoprecipitation using a H3K27me3-specific antibody followed by DNA quantification by PCR showed a strong DNA enrichment - indicating that NOS2 is associated with H3K27me3 in human umbilical vein endothelial cells (HUVEC). siRNA mediated knock down of Ezh2 diminished NOS2 DNA enrichment - suggesting that the association of NOS2 with H3K27me3 is mediated by Ezh2. Ezh2 knock down, however, was not sufficient to increase iNOS expression after stimulation of HUVEC. CONCLUSION: NOS2 is associated with Ezh2-mediated H3K27me3 in HUVEC. This might contribute to an epigenetic suppression of iNOS inducibility in human endothelial cells. PMID- 26853882 TI - Comparison of design strategies for alpha-helix backbone modification in a protein tertiary fold. AB - We report here the comparison of five classes of unnatural amino acid building blocks for their ability to be accommodated into an alpha-helix in a protein tertiary fold context. High-resolution structural characterization and analysis of folding thermodynamics yield new insights into the relationship between backbone composition and folding energetics in alpha-helix mimetics and suggest refined design rules for engineering the backbones of natural sequences. PMID- 26853883 TI - Kruppel-like factor 2 promotes cell proliferation in hepatocellular carcinoma through up-regulation of c-myc. AB - Members of kruppel-like factor family have been shown to play critical roles in the development, metabolism and tumorigenesis. Our previous study demonstrated that up-regulationupregulation of KLF2 in livers from obese mice could promote hepatosteatosis. However, little is known about its effects in hepatocellular carcinogenesis. In the present study, we found that mRNA and protein expression of KLF2 was increased in primary HCC, when compared with that in adjacent normal liver. In vitro studies further showed that enforced overexpression of KLF2 expression enhanced, while its knockdown inhibited cell proliferation and invasion. At the molecular level, c-myc was a direct transcriptional target of KLF2 and a KLF2-binding site in the c-myc promoter bound specifically to KLF2 protein. Indeed, ablation of c-myc largely attenuated the proliferative roles of KLF2 in HCC cells. Therefore, our data highlight an important role for KLF2/c-myc pathway in HCC development and progression. PMID- 26853884 TI - FISH and AgNor mapping of the 45S and 5S rRNA genes in wild and cultivated species of Capsicum (Solananceae). AB - Chromosome number and position of rDNA were studied in 12 wild and cultivated species of the genus Capsicum with chromosome numbers x = 12 and x = 13 (22 samples). For the first time in these species, the 5S and 45S rRNA loci were localized and physically mapped using two-color fluorescence in situ hybridization and AgNOR banding. We focused on the comparison of the results obtained with both methods with the aim of accurately revealing the real functional rRNA genes. The analyzes were based on a previous work that reported that the 18S-5.8S-25S loci mostly coincide with GC-rich heterochromatic regions and likely have given rise to satellite DNAs, which are not active genes. These data show the variability of rDNA within karyotypes of the genus Capsicum, providing anchor points for (comparative) genetic maps. In addition, the obtained information might be useful for studies on evolution of repetitive DNA. PMID- 26853885 TI - Anthropometric Correlation with Metabolic Syndrome in Sarajevo Population. AB - BACKGROUND: Metabolic syndrome, described as one of the most common clustering metabolic risk factors in the world, combines minimum three of the following five risk factors: central obesity, elevated fasting glucose, lipid disorders, arterial hypertension and high serum triglycerides. International Diabetes Federation (IDF) in 2009 defined abdominal obesity as the waist circumference of >=80 cm in women and >= 94 cm in men. The research goal of this study is to analyze the anthropometric risk factors for metabolic syndrome, their correlation and effects on metabolic indices related to metabolic syndrome in the analyzed population. METHODS: The study population consisted of 90 patients (51 males and 39 females). Total cholesterol, triglycerides, glucose, body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressure were measured in all patients. RESULTS: In the complete study group, WC was found to be significantly correlated with BMI (R = 0. 67, P < 0. 001). Furthermore the correlation analysis significantly confirmed positive association between BMI and WC, where other cardiovascular risk factors significantly increased with increasing BMI. CONCLUSION: Our results show linear correlation between waist circumference and body mass index, suggesting that the presence of MetSy is seen in both healthy males and female in Sarajevo population.This research indicates and confirms that WC and BMI together are good indicators of health risks in both women and men. PMID- 26853888 TI - Interconnections between Left Atrial Ganglionic Plexi: Insights from Minimally Invasive Maze Procedures and Their Outcomes. AB - BACKGROUND: Ganglionic plexi (GPs) have been implicated as triggers of atrial fibrillation (AF) and are known to have functional interconnections. Understanding these connections could result in a more effective ablation. The objective of this study is to assess relationships between right- and left-sided GPs in patients undergoing mini-maze (MM) surgery. We also analyzed the impact of these findings on AF recurrence. METHODS: The GPs were accessed thoracoscopically right side first (group 1) or left side first (group 2). GPs were identified by high-frequency stimulation at 20 predetermined sites and ablation of GPs was performed using a selective or an empiric anatomic approach. Ganglionic plexus (GP) activity was then assessed on the contralateral side and ablated. RESULTS: Sixty-seven patients underwent MM (45 patients in group 1 and 22 in group 2). Fewer patients with active left GPs (LGP) were noted in group 1 (13, 29%) as compared to group 2 (18, 82%). The number of active LGP was also lower (0.6 +/- 1.2) in group 1 compared to group 2 (4.7 +/- 2.7); P < 0.0001. No significant differences were noted in the frequency of identifiable right GPs (RGP) between groups 1 and 2 (P > 0.05). There were no differences in atrial tachyarrhythmia (AT)/AF recurrence rates between groups 1 and 2 (P = 0.21). However, group 1 patients who underwent selective GP ablation alone had higher recurrence rates (P = 0.016). CONCLUSION: Mapping and ablation of RGPs first decreased identifiable LGP activity. With selective GP ablation, patients who underwent RGP ablation first had higher AT/AF recurrence. PMID- 26853889 TI - A Comment on "Bariatric Surgery in Type 1 Diabetes Mellitus: a Systematic Review". PMID- 26853890 TI - Regionally progressive accumulation of iron in Parkinson's disease as measured by quantitative susceptibility mapping. AB - The progression of Parkinson's disease (PD) seems to vary according to the disease stage, which greatly influences the management of PD patients. However, the underlying mechanism of progression in PD remains unclear. This study was designed to explore the progressive pattern of iron accumulation at different stages in PD patients. Sixty right-handed PD patients and 40 normal controls were recruited. According to the disease stage, 45 patients with Hoehn-Yahr stage <= 2.5 and 15 patients with Hoehn-Yahr stage >= 3 were grouped into early-stage PD (EPD) and late-stage PD (LPD) groups, respectively. The iron content in the cardinal subcortical nuclei covering the cerebrum, cerebellum and midbrain was measured using quantitative susceptibility mapping (QSM). The substantia nigra pars compacta (SNc) showed significantly increased QSM values in the EPD patients compared with the controls. In the LPD patients, while the SNc continued to show increased QSM values compared with the controls and EPD patients, the regions showing increased QSM values spread to include the substantia nigra pars reticulata (SNr), red nucleus (RN) and globus pallidus (GP). Our data also indicated that iron deposition was more significant in the GP internal segment (GPi) than in the GP external segment. No other regions showed significant changes in QSM values among the groups. Therefore, we were able to confirm a regionally progressive pattern of iron accumulation in the different stages of PD, indicating that iron deposition in the SNc is affected exclusively in the early stages of the disease, while the SNr, RN and GP, and particularly the GPi segment, become involved in advanced stages of the disease. This is a preliminary study providing objective evidence of the iron-related progression in PD. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26853891 TI - Sleep mediates the link between resiliency and behavioural problems in children at high and low risk for alcoholism. AB - Children of alcoholic parents are at greater risk for developing substance use problems. Having a parent with any mental illness increases the risk for sleep disorders in children. Using actigraphy, this study characterized sleep in children of alcoholics and community controls over a period of 1 week. This study further examined whether sleep characteristics of the children mediated the relationship between self-regulation indices (i.e. undercontrol and resiliency) and outcome measures of function (e.g. problem behaviours and perceived conflict at home). Eighty-two children (53 boys, 29 girls, 7.2-13.0 years old) were recruited from the ongoing Michigan Longitudinal Study. Seventeen participants had no parental history of alcohol abuse or dependence family history negative (FH-), 43 had at least one parent who was a recovered alcoholic, and 22 had at least one parent who met diagnostic criteria within the past 3 years. Sleep was assessed with actigraphy and sleep diaries for 1 week, and combined with secondary analysis of data collected for the longitudinal study. FH- children had more objectively measured total sleep time. More total sleep time was associated with greater resiliency and behavioural control, fewer teacher-reported behavioural problems, and less child-reported conflict at home. Further, total sleep time partially mediated the relationship between resiliency and perceived conflict, and between resiliency and externalizing problems. These findings suggest that in high-risk homes, the opportunity to obtain sufficient sleep is reduced, and that insufficient sleep further exacerbates the effects of impaired dispositional self-regulatory capacity on behavioural and emotional regulation. PMID- 26853892 TI - Polyunsaturated fatty acids and type 2 diabetes: Impact on the glycemic control mechanism. AB - There is a growing mortality related to co-morbidities associated with diabetes mellitus. Intake of polyunsaturated fatty acids (PUFA) has been associated with low cardiometabolic risk and reduction of inflammatory process. The objective of this paper is to review the impact of PUFA intake on glycemic control in diabetic patients as well as to elucidate the possible mechanisms involved. Medline/PubMed electronic database was searched to identify studies published within last five years regarding the effect of PUFA intake on glucose metabolism in type 2 diabetics. The search terms used were "polyunsaturated fatty acid(s)," "PUFA," and "diabetes." We included only interventional studies that assessed the effects of PUFA intake on glucose metabolism - fasting glucose, serum insulin, HbA1c, and HOMA-IR assessment- in type 2 diabetics. Initially, 48 articles were identified, of which one was not available and 41 did not match the inclusion criteria. Within the selected studies, three articles showed an improvement in fasting blood glucose, two showed an increase in fasting glycemia, and there was no effect of intervention in one article only. Based on the analyzed clinical interventional studies, supplementation of 0.42-5.2-g PUFA/day for at least eight weeks may become an alternative treatment for type 2 diabetes mellitus, particularly in Asian subjects. PMID- 26853893 TI - AGEs in human lens capsule promote the TGFbeta2-mediated EMT of lens epithelial cells: implications for age-associated fibrosis. AB - Proteins in basement membrane (BM) are long-lived and accumulate chemical modifications during aging; advanced glycation endproduct (AGE) formation is one such modification. The human lens capsule is a BM secreted by lens epithelial cells. In this study, we have investigated the effect of aging and cataracts on the AGE levels in the human lens capsule and determined their role in the epithelial-to-mesenchymal transition (EMT) of lens epithelial cells. EMT occurs during posterior capsule opacification (PCO), also known as secondary cataract formation. We found age-dependent increases in several AGEs and significantly higher levels in cataractous lens capsules than in normal lens capsules measured by LC-MS/MS. The TGFbeta2-mediated upregulation of the mRNA levels (by qPCR) of EMT-associated proteins was significantly enhanced in cells cultured on AGE modified BM and human lens capsule compared with those on unmodified proteins. Such responses were also observed for TGFbeta1. In the human capsular bag model of PCO, the AGE content of the capsule proteins was correlated with the synthesis of TGFbeta2-mediated alpha-smooth muscle actin (alphaSMA). Taken together, our data imply that AGEs in the lens capsule promote the TGFbeta2-mediated fibrosis of lens epithelial cells during PCO and suggest that AGEs in BMs could have a broader role in aging and diabetes-associated fibrosis. PMID- 26853894 TI - Resistant cytomegalovirus in intestinal and multivisceral transplant recipients. AB - BACKGROUND: Intestinal and multivisceral transplantation can be complicated by cytomegalovirus (CMV)-related viremia and disease. Intravenous ganciclovir (GCV) and oral valganciclovir remain the treatment of choice in this setting. Limited data are available on GCV-resistant (GCV-R) CMV infection in small intestine and multivisceral transplant recipients. METHOD: A retrospective review was performed on all patients who underwent small intestine or multivisceral transplantation from November 8, 2003 through November 30, 2008. Those with CMV viremia and invasive disease were identified. GCV resistance was suspected in patients who continued to have viremic episodes or invasive disease despite appropriate GCV treatment. Genotypic analyses were performed to detect the presence of GCV resistance genes UL97 and UL54. RESULTS: During the study period, 88 small intestine or multivisceral transplants were performed on 85 patients. Of the 88 transplantations, 16 patients developed CMV viremia with or without end-organ disease (18.2%) and 5.7% developed GCV-R CMV infection. In patients diagnosed with CMV infection, 31.3% (5/16) had GCV-R CMV infection. Of patients with GCV-R CMV infection, 80% (4/5) developed CMV allograft enteritis, resulting in allograft explantation in 3 patients. All patients with GCV-R CMV infection were CMV donor positive/recipient negative. Patients with tissue-invasive CMV disease were 18 times more likely to be infected with GCV-R CMV (95% confidence interval 1.24-260.93; P-value 0.0341). CONCLUSION: Small intestinal and multivisceral transplant recipients have a higher rate of GCV-R CMV infection compared with other solid organ transplant recipients, which is often associated with tissue invasive disease and allograft loss. PMID- 26853895 TI - Breech presentation is a risk factor for dysplasia of the femoral trochlea. PMID- 26853896 TI - Scoping review: national monitoring frameworks for social determinants of health and health equity. AB - BACKGROUND: The strategic importance of monitoring social determinants of health (SDH) and health equity and inequity has been a central focus in global discussions around the 2011 Rio Political Declaration on SDH and the Millennium Development Goals. This study is part of the World Health Organization (WHO) equity-oriented analysis of linkages between health and other sectors (EQuAL) project, which aims to define a framework for monitoring SDH and health equity. OBJECTIVES: This review provides a global summary and analysis of the domains and indicators that have been used in recent studies covering the SDH. These studies are considered here within the context of indicators proposed by the WHO EQuAL project. The objectives are as follows: to describe the range of international and national studies and the types of indicators most frequently used; report how they are used in causal explanation of the SDH; and identify key priorities and challenges reported in current research for national monitoring of the SDH. DESIGN: We conducted a scoping review of published SDH studies in the PubMed((r)) database to obtain evidence of socio-economic indicators. We evaluated, selected, and extracted data from national scale studies published from 2004 to 2014. The research included papers published in English, Italian, French, Portuguese, and Spanish. RESULTS: The final sample consisted of 96 articles. SDH monitoring is well reported in the scientific literature independent of the economic level of the country and magnitude of deprivation in population groups. The research methods were mostly quantitative and many papers used multilevel and multivariable statistical analyses and indexes to measure health inequalities and SDH. In addition to the usual economic indicators, a high number of socio economic indicators were used. The indicators covered a broad range of social dimensions, which were given consideration within and across different social groups. Many indicators included in the WHO EQuAL framework were not common in the studies in this review due to their intersectoral and interdisciplinary nature. CONCLUSIONS: Our review illustrates that the attention to SDH monitoring has grown in terms of its importance and complexity within the scientific health literature. We identified a need to make indicators more wide-ranging in order to include a broader range of social conditions. The WHO EQuAL framework can provide intersectoral and interdisciplinary means of building a more comprehensive standardised approach to monitoring the SDH and improving equity in health. PMID- 26853897 TI - The feasibility of measuring and monitoring social determinants of health and the relevance for policy and programme - a qualitative assessment of four countries. AB - BACKGROUND: Since the publication of the reports by the Commission on Social Determinants of Health (CSDH), many research papers have documented inequities, explaining causal pathways in order to inform policy and programmatic decision making. At the international level, the sustainable development goals (SDGs) reflect an attempt to bring together these themes and the complexities involved in defining a comprehensive development framework. However, to date, much less has been done to address the monitoring challenges, that is, how data generation, analysis and use are to become routine tasks. OBJECTIVE: To test proposed indicators of social determinants of health (SDH), gender, equity, and human rights with respect to their relevance in tracking progress in universal health coverage and population health (level and distribution). DESIGN: In an attempt to explore these monitoring challenges, indicators covering a wide range of social determinants were tested in four country case studies (Bangladesh, Brazil, South Africa, and Vietnam) for their technical feasibility, reliability, and validity, and their communicability and usefulness to policy-makers. Twelve thematic domains with 20 core indicators covering different aspects of equity, human rights, gender, and SDH were tested through a review of data sources, descriptive analyses, key informant interviews, and focus group discussions. To test the communicability and usefulness of the domains, domain narratives that explained the causal pathways were presented to policy-makers, managers, the media, and civil society leaders. RESULTS: For most countries, monitoring is possible, as some data were available for most of the core indicators. However, a qualitative assessment showed that technical feasibility, reliability, and validity varied across indicators and countries. Producing understandable and useful information proved challenging, and particularly so in translating indicator definitions and data into meaningful lay and managerial narratives, and effectively communicating links to health and ways in which the information could improve decision-making. CONCLUSIONS: This exercise revealed that for monitoring to produce reliable data collection, analysis, and discourse, it will need to be adapted to each national context and institutionalised into national systems. This will require that capacities and resources for this and subsequent communication of results are increased across countries for both national and international monitoring, including the successful implementation of the SDGs. PMID- 26853898 TI - Assessing the relevance of indicators in tracking social determinants and progress toward equitable population health in Brazil. AB - BACKGROUND: The importance of the social determinants of health (SDH) and barriers to the access and utilization of healthcare have been widely recognized but not previously studied in the context of universal healthcare coverage (UHC) in Brazil and other developing countries. OBJECTIVE: To evaluate a set of proposed indicators of SDH and barriers to the access and utilization of healthcare - proposed by the SDH unit of the World Health Organization - with respect to their relevance in tracking progress in moving toward equitable population health and UHC in Brazil. DESIGN: This study had a mixed methodology, combining a quantitative analysis of secondary data from governmental sources with a qualitative study comprising two focus group discussions and six key informant interviews. The set of indicators tested covered a broad range of dimensions classified by three different domains: environment quality; accountability and inclusion; and livelihood and skills. Indicators were stratified according to income quintiles, urbanization, race, and geographical region. RESULTS: Overall, the indicators were adequate for tracking progress in terms of the SDH, equity, gender, and human rights in Brazil. Stratifications showed inequalities. The qualitative analysis revealed that many of the indicators were well known and already used by policymakers and health sector managers, whereas others were considered less useful in the Brazilian context. CONCLUSIONS: Monitoring and evaluation practices have been developed in Brazil, and the set of indicators assessed in this study could further improve these practices, especially from a health equity perspective. Socioeconomic inequalities have been reduced in Brazil in the last decade, but there is still much work to be done in relation to addressing the SDH. PMID- 26853899 TI - Dementia in Parkinson's disease is associated with enhanced mitochondrial complex I deficiency. AB - BACKGROUND: Dementia is a common feature of Parkinson's disease (PD), but the neuropathological changes associated with the development of Parkinson's disease dementia (PDD) are only partially understood. Mitochondrial dysfunction is a hallmark of PD but has not been studied in PDD. METHODS: Molecular and biochemical approaches were used to study mitochondrial activity and quantity in postmortem prefrontal cortex tissue. Tissues from pathologically confirmed PD and PDD patients and from age-matched controls were used to analyze the activity of mitochondrial enzyme complex nicotinamide adenine dinucleotide:ubiquinone oxidoreductase, or complex I (the first enzyme in the mitochondrial respiratory chain), mitochondrial DNA levels, and the expression of mitochondrial proteins. RESULTS: Complex I activity was significantly decreased (27% reduction; analysis of variance with Tukey's post hoc test; P < 0.05) in PDD patients, and mitochondrial DNA levels were also significantly decreased (18% reduction; Kruskal-Wallis analysis of variance with Dunn's multiple comparison test; P < 0.05) in PDD patients compared with controls, but neither was significantly reduced in PD patients. Overall, mitochondrial biogenesis was unaffected in PD or PDD, because the expression of mitochondrial proteins in patients was similar to that in controls. CONCLUSIONS: Patients with PDD have a deficiency in mitochondrial complex I activity and reduced mitochondrial DNA levels in the prefrontal cortex without a change in mitochondrial protein quantity. Therefore, mitochondrial complex I deficiency and reduced mitochondrial DNA in the prefrontal cortex may be a hallmark of dementia in patients with PD. PMID- 26853901 TI - TCNQ Interlayers for Colloidal Quantum Dot Light-Emitting Diodes. AB - CdSe/CdS/ZnS quantum dot light-emitting diodes (QD-LEDs) show increased brightness (from ca. 18 000 to 27 000 cd m(-2) ) with 7,7,8,8 tetracyanoquinodimethane (TCNQ) between the QD and electron-transfer layers of ZnO nanoparticles. As QD/ZnO layers are known to have interface defects, our finding leads to the importance of interface engineering for QD-LEDs. Although the photoluminescent intensity and decay lifetime of ZnO/TCNQ/QD layers are similar to those of ZnO/QD layers, cyclic voltammetry suggests improved charge transfer of TCNQ/ZnO layers compared to that of pure ZnO layers. This helps us to understand the mechanism of electrically driven QD-LED behavior, which differs from that of conventional solid-state LEDs, and enables the rational design of QD based optoelectronic devices. PMID- 26853902 TI - Cryoballoon ablation for atrial fibrillation - is cryoenergy applied only to the pulmonary vein ostium? AB - This case report shows that cryoablation of pulmonary veins (PV) may occasionally result in deeper lesions than expected and collateral damage in spite of proper ostial positioning of cryoballoon. The use of intracardiac vascular ultrasound and repeated computed tomography enabled detailed examination of these findings. PMID- 26853900 TI - Diagnostic value of recombinant Tp0821 protein in serodiagnosis for syphilis. AB - Syphilis is a multistage sexually transmitted disease that remains a serious public health concern worldwide. The coexistence of Treponema pallidum with other closely related members of spirochaeta, such as Leptospira spp. and Borrelia burgdorferi, has complicated the serodiagnosis due to cross-reactive antigens. In this study, recombinant Tp0821 protein was expressed in Escherichia coli and purified by metal affinity chromatography. Then enzyme-linked immunosorbent assays (ELISAs) based on Tp0821 for the detection of specific antibodies were established. The relative positive rates of the IgM ELISA and the IgG ELISA were found to be 91.0 and 98.3%, respectively, when screening 578 syphilis specimens. The specificities were 94.3 and 100%, respectively, when cross-checking with serum samples obtained from 30 patients with Lyme disease, five patients with leptospirosis, and 52 uninfected controls. In addition, relative positive rates and specificities of Tp0821 for human sera were all 100% in Western blotting. When compared to the syphilis diagnostic tests commonly used in clinical settings, we found that the results of Tp0821-based ELISAs correlated well with the results of the treponemal tests, specifically the T. pallidum particle agglutination (TP-PA) test and the chemiluminescent immunoassay (CIA). Thus, these findings identify Tp0821 as a novel serodiagnostic candidate for syphilis. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we expressed and purified the Treponema pallidum protein Tp0821 and developed Tp0821-based enzyme-linked immunosorbent assays (ELISAs) for the detection of specific antibodies. The serodiagnostic performance of the recombinant protein was then evaluated. When compared to the results of syphilis diagnostic tests commonly used in clinical settings, we found that the reactivities of syphilitic sera with the recombinant antigen correlated well with the results of the treponemal tests, specifically the T. pallidum particle agglutination (TP-PA) test and the chemiluminescent immunoassay (CIA). Thus, the recombinant protein shows promise as a new diagnostic antigen in the ELISAs. PMID- 26853903 TI - IgE and FcepsilonRI are highly expressed on innate cells in psoriasis. AB - BACKGROUND: Although elevated serum IgE levels have been reported in psoriasis, the role of IgE in psoriasis still needs to be clarified. OBJECTIVES: To analyse serum total IgE levels in addition to the presence and distribution of IgE and FcepsilonRI in psoriatic lesions, and to investigate alteration of IgE and FcepsilonRI after successful systemic treatment. METHODS: Total serum IgE levels were determined using enzyme-linked immunosorbent assay. The expression and localization of IgE and FcepsilonRI was investigated using immunohistochemistry and double immunofluorescence. RESULTS: Elevated total serum IgE levels were found in 39% of patients with psoriasis. The levels of total serum IgE were significantly higher in male patients compared with female patients. Furthermore, total serum IgE levels decreased after successful systemic treatment. A positive correlation between IgE+ and FcepsilonRI+ cells and a significant increase of these cells was found in psoriatic lesions when compared with normal skin. Interestingly, IgE+ and FcepsilonRI+ cells decreased significantly after successful therapy with ustekinumab. IgE and FcepsilonRI were coexpressed on mast cells, epidermal Langerhans cells, dermal dendritic cells, macrophages and a small number of neutrophils. CONCLUSIONS: IgE might participate in the development of psoriasis by activating FcepsilonRI-bearing cells. PMID- 26853905 TI - Response to "Metabolic improvement with fructose restriction: Is it the fructose or the weight loss?". PMID- 26853904 TI - Abnormal salience signaling in schizophrenia: The role of integrative beta oscillations. AB - Aberrant salience attribution and cerebral dysconnectivity both have strong evidential support as core dysfunctions in schizophrenia. Aberrant salience arising from an excess of dopamine activity has been implicated in delusions and hallucinations, exaggerating the significance of everyday occurrences and thus leading to perceptual distortions and delusional causal inferences. Meanwhile, abnormalities in key nodes of a salience brain network have been implicated in other characteristic symptoms, including the disorganization and impoverishment of mental activity. A substantial body of literature reports disruption to brain network connectivity in schizophrenia. Electrical oscillations likely play a key role in the coordination of brain activity at spatially remote sites, and evidence implicates beta band oscillations in long-range integrative processes. We used magnetoencephalography and a task designed to disambiguate responses to relevant from irrelevant stimuli to investigate beta oscillations in nodes of a network implicated in salience detection and previously shown to be structurally and functionally abnormal in schizophrenia. Healthy participants, as expected, produced an enhanced beta synchronization to behaviorally relevant, as compared to irrelevant, stimuli, while patients with schizophrenia showed the reverse pattern: a greater beta synchronization in response to irrelevant than to relevant stimuli. These findings not only support both the aberrant salience and disconnectivity hypotheses, but indicate a common mechanism that allows us to integrate them into a single framework for understanding schizophrenia in terms of disrupted recruitment of contextually appropriate brain networks. PMID- 26853906 TI - Fine Golden Rings: Tunable Surface Plasmon Resonance from Assembled Nanorods in Topological Defects of Liquid Crystals. AB - Unprecedented, reversible, and dynamic control over an assembly of gold nanorods dispersed in liquid crystals (LC) is demonstrated. The LC director field is dynamically tuned at the nanoscale using microscale ring confinement through the interplay of elastic energy at different temperatures, thus fine-tuning its core replacement energy to reversibly sequester nanoscale inclusions at the microscale. This leads to shifts of 100 nm or more in the surface plasmon resonance peak, an order of magnitude greater than any previous work with AuNR composites. PMID- 26853907 TI - Generation of TALE nickase-mediated gene-targeted cows expressing human serum albumin in mammary glands. AB - Targeting exogenous genes at milk protein loci via gene-targeting technology is an ideal strategy for producing large quantities of pharmaceutical proteins. Transcription-activator-like effector (TALE) nucleases (TALENs) are an efficient genome-editing tool. However, the off-target effects may lead to unintended gene mutations. In this study, we constructed TALENs and TALE nickases directed against exon 2 of the bovine beta-lactoglobulin (BLG) locus. The nickases can induce a site-specific DNA single-strand break, without inducing double-strand break and nonhomologous end joining mediated gene mutation, and lower cell apoptosis rate than TALENs. After co-transfecting the bovine fetal fibroblasts with human serum albumin (HSA) gene-targeting vector and TALE nickase expression vectors, approximately 4.8% (40/835) of the cell clones contained HSA at BLG locus. Unexpectedly, one homozygous gene-targeted cell clone (1/835, 0.1%) was obtained by targeting both alleles of BLG in a single round of transfection. The recombinant protein mimicking the endogenous BLG was highly expressed and correctly folded in the mammary glands of the targeted cows, and the expression level of HSA was significantly increased in the homozygous targeted cows. Results suggested that the combination of TALE nickase-mediated gene targeting and somatic cell nuclear transfer is a feasible and safe approach in producing gene targeted livestock. PMID- 26853908 TI - Comparative analyses of fungicide sensitivity and SSR marker variations indicate a low risk of developing azoxystrobin resistance in Phytophthora infestans. AB - Knowledge of the evolution of fungicide resistance is important in securing sustainable disease management in agricultural systems. In this study, we analyzed and compared the spatial distribution of genetic variation in azoxystrobin sensitivity and SSR markers in 140 Phytophthora infestans isolates sampled from seven geographic locations in China. Sensitivity to azoxystrobin and its genetic variation in the pathogen populations was measured by the relative growth rate (RGR) at four fungicide concentrations and determination of the effective concentration for 50% inhibition (EC50). We found that all isolates in the current study were sensitive to azoxystrobin and their EC50 was similar to that detected from a European population about 20 years ago, suggesting the risk of developing azoxystrobin resistance in P. infestans populations is low. Further analyses indicate that reduced genetic variation and high fitness cost in resistant mutations are the likely causes for the low evolutionary likelihood of developing azoxystrobin resistance in the pathogen. We also found a negative correlation between azoxystrobin tolerance in P. infestans populations and the mean annual temperature of collection sites, suggesting that global warming may increase the efficiency of using the fungicide to control the late blight. PMID- 26853909 TI - Nitric Oxide Prevents Mouse Embryonic Stem Cell Differentiation Through Regulation of Gene Expression, Cell Signaling, and Control of Cell Proliferation. AB - Nitric oxide (NO) delays mouse embryonic stem cell (mESC) differentiation by regulating genes linked to pluripotency and differentiation. Nevertheless, no profound study has been conducted on cell differentiation regulation by this molecule through signaling on essential biological functions. We sought to demonstrate that NO positively regulates the pluripotency transcriptional core, enforcing changes in the chromatin structure, in addition to regulating cell proliferation, and signaling pathways with key roles in stemness. Culturing mESCs with 2 MUM of the NO donor diethylenetriamine/NO (DETA/NO) in the absence of leukemia inhibitory factor (LIF) induced significant changes in the expression of 16 genes of the pluripotency transcriptional core. Furthermore, treatment with DETA/NO resulted in a high occupancy of activating H3K4me3 at the Oct4 and Nanog promoters and repressive H3K9me3 and H3k27me3 at the Brachyury promoter. Additionally, the activation of signaling pathways involved in pluripotency, such as Gsk3-beta/beta-catenin, was observed, in addition to activation of PI3 K/Akt, which is consistent with the protection of mESCs from cell death. Finally, a decrease in cell proliferation coincides with cell cycle arrest in G2/M. Our results provide novel insights into NO-mediated gene regulation and cell proliferation and suggest that NO is necessary but not sufficient for the maintenance of pluripotency and the prevention of cell differentiation. J. Cell. Biochem. 117: 2078-2088, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26853910 TI - Timing for dose-down of 5-ASA depends on mucosal status with ulcerative colitis. AB - OBJECTIVE: Although aminosalicylic acid (ASA) preparations have been used as first-line drugs for the treatment of ulcerative colitis (UC), no consistent view has been established regarding the ASA dose during the remission-maintenance phase of the disease. In this study, we examined whether the ASA dose should be reduced during the remission-maintenance phase. MATERIALS AND METHODS: This study included 203 patients in the remission-maintenance phase of UC. The Mayo endoscopic subscore (MES) was used to evaluate mucosa. Comparison and analysis were performed between patients whose ASA dose had been unchanged and whose dose had been reduced, between patients with endoscopic healing (EH) group and those without endoscopic healing (WEH) group, and between patients with an MES of 0 and 1. RESULTS: Comparison between the unchanged-ASA and reduced-ASA groups revealed that the remission-maintenance rate was higher in the unchanged-ASA group (p < 0.001). Next, the remission-maintenance rate was higher in the EH/unchanged-ASA group than in the EH/reduced-ASA group (p = 0.042). Comparison between the MES 0 and 1 groups revealed that the remission-maintenance rate was higher in the MES 0 group (p = 0.007). In addition, no significant difference in remission maintenance rates was observed between the MES 0/unchanged-ASA group and the MES 0/reduced-ASA group (p = 0.108). CONCLUSION: When the same ASA dose is maintained regardless of the presence or absence of EH, remission is more likely to be maintained. If the ASA dose must be reduced, dose reduction is more advantageous after an MES of 0 is achieved. PMID- 26853912 TI - Storage of platelets at 4 degrees C in platelet additive solutions prevents aggregate formation and preserves platelet functional responses. AB - BACKGROUND: Platelet (PLT) storage has been limited to 5 days at room temperature due to metabolic decline and risk for bacterial contamination. Refrigeration preserves PLT metabolism and function as well as limits bacterial growth; however, cold storage of PLTs also leads to aggregate formation. We hypothesized that storage of PLT concentrates at 4 degrees C leads to glycoprotein (GP)IIb IIIa activation and thus aggregate formation through fibrinogen binding and that this could be prevented by storing PLTs in PLT additive solution (PAS) without compromising PLT function. STUDY DESIGN AND METHODS: Apheresis PLTs in plasma (AP) or apheresis PLTs in PAS were stored at 22 or 4 degrees C for up to 15 days. Measurements include PLT counts, blood gases, aggregation response, flow cytometry analysis of integrin levels, activation markers, and microparticle formation. RESULTS: Storage of AP 4 degrees C led to a gradual decline in PLT count and an increase in aggregate formation that was mediated by intracellular calcium leak and fibrinogen receptor activation. Storage of PAS at 4 degrees C prevented aggregate formation due to dilution of plasma fibrinogen. PAS stored at 4 degrees C maintained aggregation responses to multiple agonists better than 22 degrees C controls. CONCLUSION: Storage of AP at 4 degrees C leads to low level GPIIb-IIIa activation and results in aggregate formation over time. Separating the PLTs from the plasma component and storing them in PAS at 4 degrees C resolves aggregate formation and preserves the metabolic and functional responses of these stored PLTs. PMID- 26853911 TI - The Protein Corona of Plant Virus Nanoparticles Influences their Dispersion Properties, Cellular Interactions, and In Vivo Fates. AB - Biomolecules in bodily fluids such as plasma can adsorb to the surface of nanoparticles and influence their biological properties. This phenomenon, known as the protein corona, is well established in the field of synthetic nanotechnology but has not been described in the context of plant virus nanoparticles (VNPs). The interaction between VNPs derived from Tobacco mosaic virus (TMV) and plasma proteins is investigated, and it is found that the VNP protein corona is significantly less abundant compared to the corona of synthetic particles. The formed corona is dominated by complement proteins and immunoglobulins, the binding of which can be reduced by PEGylating the VNP surface. The impact of the VNP protein corona on molecular recognition and cell targeting in the context of cancer and thrombosis is investigated. A library of functionalized TMV rods with polyethylene glycol (PEG) and peptide ligands targeting integrins or fibrin(ogen) show different dispersion properties, cellular interactions, and in vivo fates depending on the properties of the protein corona, influencing target specificity, and non-specific scavenging by macrophages. Our results provide insight into the in vivo properties of VNPs and suggest that the protein corona effect should be considered during the development of efficacious, targeted VNP formulations. PMID- 26853913 TI - Optogenetic control of nuclear protein export. AB - Active nucleocytoplasmic transport is a key mechanism underlying protein regulation in eukaryotes. While nuclear protein import can be controlled in space and time with a portfolio of optogenetic tools, protein export has not been tackled so far. Here we present a light-inducible nuclear export system (LEXY) based on a single, genetically encoded tag, which enables precise spatiotemporal control over the export of tagged proteins. A constitutively nuclear, chromatin anchored LEXY variant expands the method towards light inhibition of endogenous protein export by sequestering cellular CRM1 receptors. We showcase the utility of LEXY for cell biology applications by regulating a synthetic repressor as well as human p53 transcriptional activity with light. LEXY is a powerful addition to the optogenetic toolbox, allowing various novel applications in synthetic and cell biology. PMID- 26853914 TI - Altered Th17 Cytokine Expression in Helicobacter pylori Patients with TLR4 (D299G) Polymorphism. AB - Helicobacter pylori (H. pylori) is associated with gastric ulcer and gastric adenocarcinoma. Polymorphisms in the host genes coding for Toll-like receptors (TLRs) may influence the innate and adaptive immune response to the infection, affecting the susceptibility to H. pylori or the disease outcomes. However, the details and association with different polymorphism and clinical expression of infection remain unclear. A case-control study consisting of 58 patients with H. pylori infection and 44 H. pylori uninfection was conducted. Genomic DNA was extracted and genotypes of TLR4 Asp299Gly polymorphism were assessed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Mucosal cytokines expression in H. pylori-infected and uninfected gastric biopsies was determined by real-time PCR. The expression of IL-6, IL-17, IL-21, IL-23 and TGF-beta1 was significantly higher in patients with D299G polymorphism in TLR4. But the expression of IL-18 between patients with single-nucleotide polymorphisms (SNPs) in TLR4 and patients with the wild-type allele was not significant. In H. pylori-infected patients with gastritis, SNPs in TLR4 may alter cytokine expression toward Th17 immune response in the gastric mucosa and may have increased risk for the development of peptic ulcer. PMID- 26853915 TI - The revised Children's Hand-use Experience Questionnaire: a handy tool for children with unilateral cerebral palsy. PMID- 26853916 TI - Galectin-3 inhibition prevents adipose tissue remodelling in obesity. AB - Extracellular matrix remodelling of the adipose tissue has a pivotal role in the pathophysiology of obesity. Galectin-3 (Gal-3) is increased in obesity and mediates inflammation and fibrosis in the cardiovascular system. However, the effects of Gal-3 on adipose tissue remodelling associated with obesity remain unclear. Male Wistar rats were fed either a high-fat diet (33.5% fat) or a standard diet (3.5% fat) for 6 weeks. Half of the animals of each group were treated with the pharmacological inhibitor of Gal-3, modified citrus pectin (MCP; 100 mg kg(-1) per day) in the drinking water. In adipose tissue, obese animals presented an increase in Gal-3 levels that were accompanied by an increase in pericellular collagen. Obese rats exhibited higher adipose tissue inflammation, as well as enhanced differentiation degree of the adipocytes. Treatment with MCP prevented all the above effects. In mature 3T3-L1 adipocytes, Gal-3 (10(-8 )m) treatment increased fibrosis, inflammatory and differentiation markers. In conclusion, Gal-3 emerges as a potential therapeutic target in adipose tissue remodelling associated with obesity and could have an important role in the development of metabolic alterations associated with obesity. PMID- 26853917 TI - The varying effects of obesity and morbid obesity on outcomes following cardiac transplantation. AB - The purpose of this study was to compare the outcomes of patients undergoing cardiac transplantation stratified by body mass index (BMI, kg m(-)(2)). The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry captured 220 cardiac transplantations in Alberta, Canada from January 2004 to April 2013. All recipients were stratified by BMI into five groups (BMI: <20, 20-24.9, 25-29.9, 30-<34.9 and ?35). Patient characteristics were analyzed by analysis of variance and chi(2) analyses. Kaplan-Meier was used to examine survival differences. Preoperative characteristics demonstrated significant increases in metabolic syndrome, prior myocardial infarction and prior coronary artery bypass graft in patients with morbid obesity. Intra-operatively, there was an increase in cardiopulmonary bypass time in patients with morbid obesity (P<0.01). Postoperative analysis revealed increased rates of early complications (<30 days), associated with a BMI >35. Long-term survival was also significantly decreased in patients with morbid obesity. Of interest, obesity (BMI, 30-34.9) was not associated with decreased survival. These findings suggest that, post cardiac transplantation, patients who have a BMI ?35 have lower long-term survival compared with all other BMI groups. However, patients with BMI 30-34.9 did not have significantly worse outcomes and should not be excluded for heart transplantation based on BMI. PMID- 26853918 TI - Artificial Life in Quantum Technologies. AB - We develop a quantum information protocol that models the biological behaviours of individuals living in a natural selection scenario. The artificially engineered evolution of the quantum living units shows the fundamental features of life in a common environment, such as self-replication, mutation, interaction of individuals, and death. We propose how to mimic these bio-inspired features in a quantum-mechanical formalism, which allows for an experimental implementation achievable with current quantum platforms. This study paves the way for the realization of artificial life and embodied evolution with quantum technologies. PMID- 26853919 TI - Bayesian multinomial probit modeling of daily windows of susceptibility for maternal PM2.5 exposure and congenital heart defects. AB - Epidemiologic studies suggest that maternal ambient air pollution exposure during critical periods of pregnancy is associated with adverse effects on fetal development. In this work, we introduce new methodology for identifying critical periods of development during post-conception gestational weeks 2-8 where elevated exposure to particulate matter less than 2.5 um (PM2.5 ) adversely impacts development of the heart. Past studies have focused on highly aggregated temporal levels of exposure during the pregnancy and have failed to account for anatomical similarities between the considered congenital heart defects. We introduce a multinomial probit model in the Bayesian setting that allows for joint identification of susceptible daily periods during pregnancy for 12 types of congenital heart defects with respect to maternal PM2.5 exposure. We apply the model to a dataset of mothers from the National Birth Defect Prevention Study where daily PM2.5 exposures from post-conception gestational weeks 2-8 are assigned using predictions from the downscaler pollution model. This approach is compared with two aggregated exposure models that define exposure as the average value over post-conception gestational weeks 2-8 and the average over individual weeks, respectively. Results suggest an association between increased PM2.5 exposure on post-conception gestational day 53 with the development of pulmonary valve stenosis and exposures during days 50 and 51 with tetralogy of Fallot. Significant associations are masked when using the aggregated exposure models. Simulation study results suggest that the findings are robust to multiple sources of error. The general form of the model allows for different exposures and health outcomes to be considered in future applications. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26853920 TI - Can the silkworm (Bombyx mori) be used as a human disease model? AB - Bombyx mori (silkworm) is the most famous lepidopteran in Japan. B. mori has long been used in the silk industry and also as a model insect for agricultural research. In recent years, B. mori has attracted interest in its potential for use in pathological analysis of model animals. For example, the human macular carotenoid transporter was discovered using information of B. mori carotenoid transporter derived from yellow-cocoon strain. The B. mori carotenoid transport system is useful in human studies. To develop a human disease model, we characterized the human homologs of B. mori, and by constructing KAIKO functional annotation pipeline, and to analyze gene expression profile of a unique B. mori mutant strain using microarray analysis. As a result, we identified a novel molecular network involved in Parkinson's disease. Here we describe the potential use of a spontaneous mutant silkworm strain as a human disease model. We also summarize recent progress in the application of genomic information for annotation of human homologs in B. mori. The B. mori mutant will provide a clue to pathological mechanisms, and the findings will be helpful for the development of therapies and for medical drug discovery. PMID- 26853921 TI - Music intervention in the acute and critical care settings: Commentary on "The effect of music during bronchoscopy: A meta-analysis". PMID- 26853922 TI - Problems and health needs of adult extracorporeal membrane oxygenation patients following hospital discharge: A qualitative study. AB - OBJECTIVES: To explore problems and health needs of adult extracorporeal membrane oxygenation (ECMO) patients during a one-year period following hospital discharge. BACKGROUND: ECMO functions as life support during treatment of advanced cardiac and respiratory failure. Knowledge regarding the problems and health needs of discharged adult patients who have undergone ECMO is lacking. METHODS: This study used a qualitative descriptive interview design. Fourteen adult ECMO patients were recruited by purposive sampling prior to discharge. Data were generated from semi-structure in-depth interviews at 3-month intervals following hospital discharge. RESULTS: Four themes described problems and needs post-discharge: stress resulting from ECMO surgery; making health a priority; support from family friends and health care professionals; and emotional support. CONCLUSIONS: Multidisciplinary evidence-based interventions should be implemented prior to or soon after discharge to help with the physical, psychological and social problems that ECMO survivors experience, which can help improve their quality of life. PMID- 26853923 TI - Vegetarian, vegan diets and multiple health outcomes: A systematic review with meta-analysis of observational studies. AB - BACKGROUND: Beneficial effects of vegetarian and vegan diets on health outcomes have been supposed in previous studies. OBJECTIVES: Aim of this study was to clarify the association between vegetarian, vegan diets, risk factors for chronic diseases, risk of all-cause mortality, incidence, and mortality from cardio cerebrovascular diseases, total cancer and specific type of cancer (colorectal, breast, prostate and lung), through meta-analysis. METHODS: A comprehensive search of Medline, EMBASE, Scopus, The Cochrane Library, and Google Scholar was conducted. RESULTS: Eighty-six cross-sectional and 10 cohort prospective studies were included. The overall analysis among cross-sectional studies reported significant reduced levels of body mass index, total cholesterol, LDL cholesterol, and glucose levels in vegetarians and vegans versus omnivores. With regard to prospective cohort studies, the analysis showed a significant reduced risk of incidence and/or mortality from ischemic heart disease (RR 0.75; 95% CI, 0.68 to 0.82) and incidence of total cancer (RR 0.92; 95% CI 0.87 to 0.98) but not of total cardiovascular and cerebrovascular diseases, all-cause mortality and mortality from cancer. No significant association was evidenced when specific types of cancer were analyzed. The analysis conducted among vegans reported significant association with the risk of incidence from total cancer (RR 0.85; 95% CI, 0.75 to 0.95), despite obtained only in a limited number of studies. CONCLUSIONS: This comprehensive meta-analysis reports a significant protective effect of a vegetarian diet versus the incidence and/or mortality from ischemic heart disease (-25%) and incidence from total cancer (-8%). Vegan diet conferred a significant reduced risk (-15%) of incidence from total cancer. PMID- 26853924 TI - Changes in heterosubtypic antibody responses during the first year of the 2009 A(H1N1) influenza pandemic. AB - Seropositivity to avian influenza (AI) via low-level antibody titers has been reported in the general population and poultry-exposed individuals, raising the question whether these findings reflect true infection with AI or cross reactivity. Here we investigated serological profiles against human and avian influenza viruses in the general population using a protein microarray platform. We hypothesized that higher antibody diversity across recent H1 and H3 influenza viruses would be associated with heterosubtypic reactivity to older pandemic- and AI viruses. We found significant heterogeneity in antibody profiles. Increased antibody diversity to seasonal influenza viruses was associated with low-level heterosubtypic antibodies to H9 and H7, but not to H5 AI virus. Individuals exposed to the recent 2009 A(H1N1) pandemic showed higher heterosubtypic reactivity. We show that there is a complex interplay between prior exposures to seasonal and recent pandemic influenza viruses and the development of heterosubtypic antibody reactivity to animal influenza viruses. PMID- 26853925 TI - Impact of wheelchair seat height on neck and shoulder range of motion during functional task performance. AB - Wheelchair users are at high risk for developing repetitive stress injuries (RSI) of the cervical spine and glenohumeral joints due to increased demands on active range of motion (AROM) when performing functional tasks from a seated position. The addition of a seat elevation device may alleviate the risk factors that lead to the development of RSI. However, there are no studies which establish that wheelchair seat height impacts upon arthrokinematic requirements at vulnerable joints. Additionally, Medicare and most insurance carriers do not cover the cost of power seat elevators because this feature has not been shown to be a "medical necessity." This study examined differences in AROM at the cervical spine and glenohumeral joint during performance of two functional tasks while seated in a wheelchair with the seat elevation feature at minimum and maximum height. Results revealed statistically significant differences in AROM requirements for cervical extension and shoulder abduction between the two wheelchair seat heights. These findings provide preliminary support for the value of the power seat elevation function in minimizing the risk of RSI at the shoulder complex and cervical spine in wheelchair users. PMID- 26853926 TI - Telemedicine to support coping resources in home-living patients diagnosed with chronic obstructive pulmonary disease: Patients' experiences. AB - Introduction The way in which telemedicine contributes to promote coping and independence might be undervalued in the development of telemedicine solutions and the implementation of telemedicine interventions. This study explored how home-living patients diagnosed with chronic obstructive pulmonary disease (COPD) experienced follow-up using telemedicine, and the extent to which the implemented technology was able to support and improve the patients' coping resources and independence. Methods A qualitative approach with individual semi-structured interviews was used. Ten patients diagnosed with COPD participated. The data were transcribed verbatim and a qualitative content analysis method was used, including analyses of the manifest and latent content of the texts. Results The participants' positive attitude to handling and understanding the technology and the positive and negative feelings related to use the technology derived the theme: "The telemedicine solution is experienced as comprehensible and manageable and provides meaning in daily life". The importance of telemedicine services that provided trust and confidence, the intervention's impact on independence and self management and the intervention's ability to support integrity and meaning in life, derived the theme: "The telemedicine intervention contributes to stress reduction caused by illness burden and facilitates living as normally as possible". Discussion The impact of a telemedicine intervention might be influenced by the experience of a technological solution that requires little effort to deal with, while it must also provide meaning in life. Furthermore, the telenurses' expertise and the intervention's flexibility, i.e. possibilities for individual adaption, might promote coping to facilitate living as normally as possible despite illness. PMID- 26853927 TI - Association of RUNX3 Methylation with Clinical Outcome and Cell Migration/Invasion in Laryngeal Squamous Cell Carcinoma. AB - This study identifies promoter methylation status of RUNX3 in 77 LSCC patient tissues and their paired adjacent healthy tissues. Hypermethylation percentage RUNX3 occurred in LSCC samples was significantly higher than that in normal tissues, as well as associated with suppression of RUNX3 expression, TNM classification of malignant tumors stage, lymph node metastasis and poor overall survival rate. Reduced methylation and increased expression of RUNX3 genes in vitro was observed and decreased cell migration was further confirmed following 5 azacytidine treatment. RUNX 3 promoter hypermethylation can lead to down regulation of RUNX3 in LSCC cancerous tissue. PMID- 26853928 TI - Passive leg raising in CPR: Increasing the effectiveness of each compression. PMID- 26853929 TI - Guttate leukoderma in Darier disease: case report and review. PMID- 26853930 TI - Reactive oxygen species generated from skeletal muscles are required for gecko tail regeneration. AB - Reactive oxygen species (ROS) participate in various physiological and pathological functions following generation from different types of cells. Here we explore ROS functions on spontaneous tail regeneration using gecko model. ROS were mainly produced in the skeletal muscle after tail amputation, showing a temporal increase as the regeneration proceeded. Inhibition of the ROS production influenced the formation of autophagy in the skeletal muscles, and as a consequence, the length of the regenerating tail. Transcriptome analysis has shown that NADPH oxidase (NOX2) and the subunits (p40(phox) and p47(phox)) are involved in the ROS production. ROS promoted the formation of autophagy through regulation of both ULK and MAPK activities. Our results suggest that ROS produced by skeletal muscles are required for the successful gecko tail regeneration. PMID- 26853931 TI - Molecular characterization, functional analysis, and defense mechanisms of two CC chemokines in Nile tilapia (Oreochromis niloticus) in response to severely pathogenic bacteria. AB - Two full-length cDNAs encoding CC chemokine genes in Nile tilapia (Oreochromis niloticus) (On-CC1 and On-CC2) were cloned and characterized. On-CC1 and On-CC2 showed signature cysteine motifs consisting of four cysteines. The expression levels of On-CC1 and On-CC2 were analyzed by RT-PCR, which showed that low expression of these two genes was only observed in the peripheral blood leukocytes (PBLs) and spleen of normal fish. Expression levels of these two molecules were quantified in 13 tissues of fish infected with virulent strains of Streptococcus agalactiae and Flavobacterium columnare. Most tissues, especially PBLs, the spleen and the liver, expressed significantly higher mRNA levels than the controls, particularly at 12 and 24 h after infection (P < 0.05). The current study strongly indicates that CC chemokine genes in Nile tilapia are crucially involved in the early immune responses to pathogens. Functional analyses clearly demonstrated that 10 and 100 MUg/ml of recombinant rOn-CC1 and rOn-CC2 proteins efficiently enhanced the phagocytic activity (in vitro) of Nile tilapia phagocytes. Finally, Southern blot analysis and searching in Ensembl databases demonstrated that two different functional CC chemokine genes and other pseudogene fragments were discovered in the Nile tilapia genome. PMID- 26853932 TI - Measurement of macrocyclic trichothecene in floor dust of water-damaged buildings using gas chromatography/tandem mass spectrometry-dust matrix effects. AB - Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used to detect fungal secondary metabolites. Detection of verrucarol, the hydrolysis product of Stachybotrys chartarum macrocyclic trichothecene (MCT), was confounded by matrix effects associated with heterogeneous indoor environmental samples. In this study, we examined the role of dust matrix effects associated with GC-MS/MS to better quantify verrucarol in dust as a measure of total MCT. The efficiency of the internal standard (ISTD, 1,12-dodecanediol), and application of a matrix matched standard correction method in measuring MCT in floor dust of water damaged buildings was additionally examined. Compared to verrucarol, ISTD had substantially higher matrix effects in the dust extracts. The results of the ISTD evaluation showed that without ISTD adjustment, there was a 280% ion enhancement in the dust extracts compared to neat solvent. The recovery of verrucarol was 94% when the matrix-matched standard curve without the ISTD was used. Using traditional calibration curves with ISTD adjustment, none of the 21 dust samples collected from water damaged buildings were detectable. In contrast, when the matrix-matched calibration curves without ISTD adjustment were used, 38% of samples were detectable. The study results suggest that floor dust of water damaged buildings may contain MCT. However, the measured levels of MCT in dust using the GC-MS/MS method could be significantly under- or overestimated, depending on the matrix effects, the inappropriate ISTD, or combination of the two. Our study further shows that the routine application of matrix-matched calibration may prove useful in obtaining accurate measurements of MCT in dust derived from damp indoor environments, while no isotopically labeled verrucarol is available. PMID- 26853933 TI - Significant improvements in InGaN/GaN nano-photoelectrodes for hydrogen generation by structure and polarization optimization. AB - The photoelectrodes based on III-nitride semiconductors with high energy conversion efficiency especially for those self-driven ones are greatly desirable for hydrogen generation. In this study, highly ordered InGaN/GaN multiple-quantum well nanorod-based photoelectrodes have been fabricated by a soft UV-curing nano imprint lithography and a top-down etching technique, which improve the incident photon conversion efficiency (IPCE) from 16% (planar structure) to 42% (@ wavelength = 400 nm). More significantly, the turn-on voltage is reduced low to 0.6 V, which indicates the possibility of achieving self-driven. Furthermore, SiO2/Si3N4 dielectric distributed Bragg reflectors are employed to further improve the IPCE up to 60%. And the photocurrent (@ 1.1 V) is enhanced from 0.37 mA/cm(2) (original planar structure) to 1.5 mA/cm(2). These improvements may accelerate the possible applications for hydrogen generation with high energy efficiency. PMID- 26853936 TI - Surface-Controlled Mono/Diselective ortho C-H Bond Activation. AB - One of the most charming and challenging topics in organic chemistry is the selective C-H bond activation. The difficulty arises not only from the relatively large bond-dissociation enthalpy, but also from the poor reaction selectivity. In this work, Au(111) and Ag(111) surfaces were used to address ortho C-H functionalization and ortho-ortho couplings of phenol derivatives. More importantly, the competition between dehydrogenation and deoxygenation drove the diversity of reaction pathways of phenols on surfaces, that is, diselective ortho C-H bond activation on Au(111) surfaces and monoselective ortho C-H bond activation on Ag(111) surfaces. The mechanism of this unprecedented phenomenon was extensively explored by scanning tunneling microscopy, density function theory, and X-ray photoelectron spectroscopy. Our findings provide new pathways for surface-assisted organic synthesis via the mono/diselective C-H bond activation. PMID- 26853934 TI - Using Xenopus laevis retinal and spinal neurons to study mechanisms of axon guidance in vivo and in vitro. AB - The intricate and precise establishment of neuronal connections in the developing nervous system relies on accurate navigation of growing axons. Since Ramon y Cajal's discovery of the growth cone, the phenomenon of axon guidance has been revealed as a coordinated operation of guidance molecules, receptors, secondary messengers, and responses driven by the dynamic cytoskeleton within the growth cone. With the advent of new and accelerating techniques, Xenopus laevis emerged as a robust model to investigate neuronal circuit formation during development. We present here the advantages of the Xenopus nervous system to our growing understanding of axon guidance. PMID- 26853938 TI - An Exquisitely Specific PDZ/Target Recognition Revealed by the Structure of INAD PDZ3 in Complex with TRP Channel Tail. AB - The vast majority of PDZ domains are known to bind to a few C-terminal tail residues of target proteins with modest binding affinities and specificities. Such promiscuous PDZ/target interactions are not compatible with highly specific physiological functions of PDZ domain proteins and their targets. Here, we report an unexpected PDZ/target binding occurring between the scaffold protein inactivation no afterpotential D (INAD) and transient receptor potential (TRP) channel in Drosophila photoreceptors. The C-terminal 15 residues of TRP are required for the specific interaction with INAD PDZ3. The INAD PDZ3/TRP peptide complex structure reveals that only the extreme C-terminal Leu of TRP binds to the canonical alphaB/betaB groove of INAD PDZ3. The rest of the TRP peptide, by forming a beta hairpin structure, binds to a surface away from the alphaB/betaB groove of PDZ3 and contributes to the majority of the binding energy. Thus, the INAD PDZ3/TRP channel interaction is exquisitely specific and represents a new mode of PDZ/target recognitions. PMID- 26853937 TI - Continuum descriptions of membranes and their interaction with proteins: Towards chemically accurate models. AB - Biological membranes deform in response to resident proteins leading to a coupling between membrane shape and protein localization. Additionally, the membrane influences the function of membrane proteins. Here we review contributions to this field from continuum elastic membrane models focusing on the class of models that couple the protein to the membrane. While it has been argued that continuum models cannot reproduce the distortions observed in fully atomistic molecular dynamics simulations, we suggest that this failure can be overcome by using chemically accurate representations of the protein. We outline our recent advances along these lines with our hybrid continuum-atomistic model, and we show the model is in excellent agreement with fully-atomistic simulations of the nhTMEM16 lipid scramblase. We believe that the speed and accuracy of continuum-atomistic methodologies will make it possible to simulate large scale, slow biological processes, such as membrane morphological changes, that are currently beyond the scope of other computational approaches. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. PMID- 26853935 TI - Making muscle: Morphogenetic movements and molecular mechanisms of myogenesis in Xenopus laevis. AB - Xenopus laevis offers unprecedented access to the intricacies of muscle development. The large, robust embryos make it ideal for manipulations at both the tissue and molecular level. In particular, this model system can be used to fate map early muscle progenitors, visualize cell behaviors associated with somitogenesis, and examine the role of signaling pathways that underlie induction, specification, and differentiation of muscle. Several characteristics that are unique to X. laevis include myogenic waves with distinct gene expression profiles and the late formation of dermomyotome and sclerotome. Furthermore, myogenesis in the metamorphosing frog is biphasic, facilitating regeneration studies. In this review, we describe the morphogenetic movements that shape the somites and discuss signaling and transcriptional regulation during muscle development and regeneration. With recent advances in gene editing tools, X. laevis remains a premier model organism for dissecting the complex mechanisms underlying the specification, cell behaviors, and formation of the musculature system. PMID- 26853939 TI - Higher-Resolution Structure of the Human Insulin Receptor Ectodomain: Multi-Modal Inclusion of the Insert Domain. AB - Insulin receptor (IR) signaling is critical to controlling nutrient uptake and metabolism. However, only a low-resolution (3.8 A) structure currently exists for the IR ectodomain, with some segments ill-defined or unmodeled due to disorder. Here, we revise this structure using new diffraction data to 3.3 A resolution that allow improved modeling of the N-linked glycans, the first and third fibronectin type III domains, and the insert domain. A novel haptic interactive molecular dynamics strategy was used to aid fitting to low-resolution electron density maps. The resulting model provides a foundation for investigation of structural transitions in IR upon ligand binding. PMID- 26853941 TI - Structural and Functional Insights into the Evolution and Stress Adaptation of Type II Chaperonins. AB - Chaperonins are essential biological complexes assisting protein folding in all kingdoms of life. Whereas homooligomeric bacterial GroEL binds hydrophobic substrates non-specifically, the heterooligomeric eukaryotic CCT binds specifically to distinct classes of substrates. Sulfolobales, which survive in a wide range of temperatures, have evolved three different chaperonin subunits (alpha, beta, gamma) that form three distinct complexes tailored for different substrate classes at cold, normal, and elevated temperatures. The larger octadecameric beta complexes cater for substrates under heat stress, whereas smaller hexadecameric alphabeta complexes prevail under normal conditions. The cold-shock complex contains all three subunits, consistent with greater substrate specificity. Structural analysis using crystallography and electron microscopy reveals the geometry of these complexes and shows a novel arrangement of the alpha and beta subunits in the hexadecamer enabling incorporation of the gamma subunit. PMID- 26853940 TI - Family-wide Structural Analysis of Human Numb-Associated Protein Kinases. AB - The highly diverse Numb-associated kinase (NAK) family has been linked to broad cellular functions including receptor-mediated endocytosis, Notch pathway modulation, osteoblast differentiation, and dendrite morphogenesis. Consequently, NAK kinases play a key role in a diverse range of diseases from Parkinson's and prostate cancer to HIV. Due to the plasticity of this kinase family, NAK kinases are often inhibited by approved or investigational drugs and have been associated with side effects, but they are also potential drug targets. The presence of cysteine residues in some NAK family members provides the possibility for selective targeting via covalent inhibition. Here we report the first high resolution structures of kinases AAK1 and BIKE in complex with two drug candidates. The presented data allow a comprehensive structural characterization of the NAK kinase family and provide the basis for rational design of selective NAK inhibitors. PMID- 26853942 TI - Crystal Structure of Deinococcus Phytochrome in the Photoactivated State Reveals a Cascade of Structural Rearrangements during Photoconversion. AB - Phytochromes are photochromic photoreceptors responsible for a myriad of red/far red light-dependent processes in plants and microorganisms. Interconversion is initially driven by photoreversible isomerization of bilin, but how this alteration directs the photostate-dependent changes within the protein to actuate signaling is poorly understood. Here, we describe the structure of the Deinococcus phytochrome photosensory module in its near complete far-red light absorbing Pfr state. In addition to confirming the 180 degrees rotation of the D pyrrole ring, the dimeric structure clearly identifies downstream rearrangements that trigger large-scale conformational differences between the dark-adapted and photoactivated states. Mutational analyses verified the importance of residues surrounding the bilin in Pfr stabilization, and protease sensitivity assays corroborated photostate alterations that propagate along the dimeric interface. Collectively, these data support a cooperative "toggle" model for phytochrome photoconversion and advance our understanding of the allosteric connection between the photosensory and output modules. PMID- 26853944 TI - [How management teams use information and control systems to manage hospitals]. AB - OBJECTIVE: To analyze the relationship between the characteristics of top management teams and the different use of management information and control systems (MICS) to implement policies that encourage cooperation and activity coordination in public hospitals. METHODS: Data were collected through a questionnaire sent to each member of the top management teams of 231 Spanish public hospitals (chief executive director, medical director, nursing director and director for financial and social issues). A total of 457 valid questionnaires were returned, composing 86 full top management teams (37.23%). RESULTS: Top management team diversity was positively related to the interactive use of MICS. Management teams composed of younger members and members with longer service used MICS interactively. Top management teams with a predominantly clinical education and experience used MICS interactively, while top teams with a predominantly administrative education and experience used MICS diagnostically. The results also showed that cooperation and coordination in hospitals were positively related to the interactive use of MICS and were negatively related to the diagnostic use of MICS. CONCLUSIONS: The interactive use of MICS is an important mediator in the relationship between top team diversity and policies focused on hospital decentralization. Top management teams with diverse characteristics (e.g. age, length of service, education and experience) use management information interactively to enhance activity coordination and resource allocation in hospitals. PMID- 26853945 TI - Doubly Resonant Optical Periodic Structure. AB - Periodic structures are well known in various branches of physics for their ability to provide a stopband. In this article, using optical periodic structures we showed that, when a second periodicity--very closed to the original periodicity is introduced, large number of states appears in the stopband corresponding to the first periodicity. In the limit where the two periods matches, we have a continuum of states, and the original stopband completely disappears. This intriguing phenomena is uncovered by noticing that, regardless of the proximities of the two periodicities, there is an array of spatial points where the dielectric functions corresponding to the two periodicities interfere destructively. These spatial points mimic photonic atoms by satisfying the standards equations of quantum harmonic oscillators, and exhibit lossless, atom like dispersions. PMID- 26853943 TI - Probing the mechanism of cardiovascular drugs using a covalent levosimendan analog. AB - One approach to improve contraction in the failing heart is the administration of calcium (Ca(2+)) sensitizers. Although it is known that levosimendan and other sensitizers bind to troponin C (cTnC), their in vivo mechanism is not fully understood. Based on levosimendan, we designed a covalent Ca(2+) sensitizer (i9) that targets C84 of cTnC and exchanged this complex into cardiac muscle. The NMR structure of the covalent complex showed that i9 binds deep in the hydrophobic pocket of cTnC. Despite slightly reducing troponin I affinity, i9 enhanced the Ca(2+) sensitivity of cardiac muscle. We conclude that i9 enhances Ca(2+) sensitivity by stabilizing the open conformation of cTnC. These findings provide new insights into the in vivo mechanism of Ca(2+) sensitization and demonstrate that directly targeting cTnC has significant potential in cardiovascular therapy. PMID- 26853946 TI - Biotechnological tools to improve bioremediation of phenol by Acinetobacter sp. RTE1.4. AB - The use of native bacteria is a useful strategy to decontaminate industrial effluents as well as the environment. Acinetobacter sp. RTE1.4 was previously isolated from polluted environments and constitutes a promising alternative for this purpose due to its capability to remove phenol from synthetic solutions and industrial effluents. In this work, this strain was identified at species level as A. tandoii RTE1.4. Phenol degradation pathway was studied and some reaction intermediates were detected, confirming that this strain degraded phenol through ortho-cleavage of the aromatic ring. Phenol removal assays were carried out in a stirred tank bioreactor and a complete degradation of the contaminant was achieved after only 7 h, at an aeration rate of 3 vvm and at agitation of 600 rpm. Moreover, this bacterium was immobilized into calcium alginate beads and an increase in phenol biodegradation with respect to free cells was observed. The immobilized cells were reused for four consecutive cycles and stored at 4 degrees C for 9 months, during which phenol removal efficiency was maintained. Post removal solutions were evaluated by Microtox(r) test, showing a toxicity reduction after bacterial treatment. These findings demonstrated that A. tandoii RTE1.4 might be considered as a useful biotechnological tool for an efficient treatment of different solutions contaminated with phenol in bioreactors, using either free or immobilized cells. PMID- 26853947 TI - Suspensory Versus Interference Screw Fixation for Arthroscopic Anterior Cruciate Ligament Reconstruction in a Translational Large-Animal Model. AB - PURPOSE: To compare all-inside cortical-button suspensory fixation in sockets versus interference screw fixation in tunnels with respect to clinical, histologic, and biomechanical assessments of all-soft tissue (AST) tendon autografts used for anterior cruciate ligament (ACL) reconstruction in a canine model. METHODS: By use of a validated "hybrid" double-bundle ACL reconstruction technique (reconstruction of the anteromedial bundle with preservation of the native posterolateral bundle), dogs were randomly assigned to undergo either suspensory fixation in sockets (n = 6) or interference screw fixation in tunnels (n = 6). Contralateral knees were used as nonoperated controls (n = 12). Quadrupled extensor tendon autografts were used for both ACL reconstruction groups. Dogs were assessed radiographically and functionally and humanely euthanized at 12 weeks after surgery for arthroscopic, gross, biomechanical, and histologic assessments. RESULTS: Histologic assessments showed significantly (P = .018) better graft incorporation with 4-zone direct healing to bone for the grafts using suspensory fixation in sockets (16.3 +/- 1.5) compared with the grafts using interference screw fixation in tunnels (14.2 +/- 2.1). Furthermore, graft healing to bone was significantly better at the aperture (P = .05) and mid socket (P = .01) location for the group that underwent suspensory fixation in sockets (16.1 +/- 1.8 and 16.4 +/- 1.9, respectively). CONCLUSIONS: Suspensory fixation of AST grafts in sockets was associated with superior tendon-to-bone healing compared with interference screw fixation in tunnels, with 4-zone direct graft healing to bone seen for femoral and tibial sockets only in the suspensory fixation group. Biomechanical properties were similar between groups. CLINICAL RELEVANCE: These data provide evidence suggesting that an all-inside ACL reconstruction technique using adjustable-loop cortical-button suspensory fixation in bone sockets has potential clinical advantages for ACL reconstruction using AST grafts. PMID- 26853948 TI - Clinical Results After Conservative Management for Grade III Acromioclavicular Joint Injuries: Does Eventual Surgery Affect Overall Outcomes? AB - PURPOSE: To compare the clinical outcomes in patients with grade III acromioclavicular (AC) joint injuries in whom nonoperative therapy was successfully completed and those who had nonoperative therapy failure and who proceeded to undergo surgical reconstruction. METHODS: Forty-nine patients were initially treated nonoperatively for grade III AC joint injuries with physical therapy. Patients completed questionnaires at initial presentation and after a follow-up period of 2 years. Outcome measures included the Short Form 12 Physical Component Score; American Shoulder and Elbow Surgeons score; Quick Disabilities of the Arm, Shoulder and Hand score; and Single Assessment Numeric Evaluation score. Failure of nonoperative treatment occurred when a patient underwent AC reconstruction before final follow-up. RESULTS: Forty-one patients with a mean age of 39 years (range, 18 to 79 years) were included. In this cohort, 29 of 41 patients (71%) successfully completed nonoperative therapy whereas 12 of 41 (30%) had nonoperative therapy failure at a median of 42 days (range, 6 days to 17.0 months). Of the 41 patients, 39 (95.3%) were contacted to determine treatment success. Of the 12 patients who had nonoperative therapy failure, 11 (92%) had sought treatment more than 30 days after the injury. Subjective follow-up data were available for 10 of 12 patients (83.3%) who had nonoperative therapy failure and for 23 of 29 patients (79.3%) who were successfully treated nonoperatively. The mean length of follow-up was 3.3 years (range, 1.8 to 5.9 years). Although there were no statistically significant differences in outcome scores between groups, those who sought treatment more than 30 days after their injury showed decreased postoperative Single Assessment Numeric Evaluation scores (P = .002) and Short Form 12 Physical Component Scores (P = .037). CONCLUSIONS: According to our results, (1) a trial of nonoperative treatment is warranted because successful outcomes can be expected even in patients who eventually opt for surgery and (2) patients who presented more than 30 days after their injury were less likely to complete nonoperative treatment successfully. LEVEL OF EVIDENCE: Level III, retrospective comparative study. PMID- 26853949 TI - Major Peripheral Nerve Injuries After Elbow Arthroscopy. AB - PURPOSE: To survey the American Society for Surgery of the Hand membership to determine the nature and distribution of nerve injuries treated after elbow arthroscopy. METHODS: An online survey was sent to all members of the American Society for Surgery of the Hand under an institutional review board-approved protocol. Collected data included the number of nerve injuries observed over a 5 year period, the nature of treatment required for the injuries, and the outcomes observed after any intervention. Responses were anonymous, and results were securely compiled. RESULTS: We obtained 372 responses. A total of 222 nerve injuries were reported. The most injured nerves reported were ulnar, radial, and posterior interosseous (38%, 22%, and 19%, respectively). Nearly half of all patients with injuries required operative intervention, including nerve graft, tendon transfer, nerve repair, or nerve transfer. Of the patients who sustained major injuries, those requiring intervention, 77% had partial or no motor recovery. All minor injuries resolved completely. CONCLUSIONS: Our results suggest that major nerve injuries after elbow arthroscopy are not rare occurrences and the risk of these injuries is likely under-reported in the literature. Furthermore, patients should be counseled on this risk because most nerve injuries show only partial or no functional recovery. With the more widespread practice of elbow arthroscopy, understanding the nature and sequelae of significant complications is critically important in ensuring patient safety and improving outcomes. PMID- 26853951 TI - Immunoglobulin K light chain deficiency: A rare, but probably underestimated, humoral immune defect. AB - Human immunoglobulin molecules are generated by a pair of identical heavy chains, which identify the immunoglobulin class, and a pair of identical light chains, Kappa or Lambda alternatively, which characterize the immunoglobulin type. In normal conditions, Kappa light chains represent approximately 2/3 of the light chains of total immunoglobulins, both circulating and lymphocyte surface bound. Very few cases of immunoglobulin Kappa or Lambda light chain defects have been reported. Furthermore, the genetic basis of this defect has been extensively explored only in a single case. We report a case of a patient suffering of serious recurrent bacterial infections, which was caused by a very rare form of immunoglobulin disorder, consisting of a pure defect of Kappa light chain. We evaluated major serum immunoglobulin concentrations, as well as total and free Kappa and Lambda light chain concentrations. Lymphocyte phenotyping was also performed and finally we tested the Kappa chain VJ rearrangement as well as the constant Kappa region sequence. Studies performed on VJ rearrangement showed a polyclonal genetic arrangement, whereas the gene sequencing for the constant region of Kappa chain showed a homozygous T to G substitution at the position 1288 (rs200765148). This mutation causes a substitution from Cys to Gly in the protein sequence and, therefore, determines the abnormal folding of the constant region of Kappa chain. We suggest that this defect could lead to an effective reduction of the variability of total antibody repertoire and a consequent defect of an apparently normal immunoglobulin response to common antigens. PMID- 26853950 TI - How does a national poverty programme influence sexual debut among Kenyan adolescents? AB - Cash transfer programmes have recently emerged as promising interventions for HIV prevention among adolescents in Africa. However, the pathways through which risk reduction occurs are not well understood. We examine data on 1429 adolescents and youth from the Kenya Cash Transfer for Orphans and Vulnerable Children, which has been shown to result in delayed sexual debut among adolescents. We explored three potential mediating pathways: schooling, socio-economic status and psycho-social status. None of these hypothesised mediators greatly altered the main effect. However, school attendance had a larger protective effect on sexual debut among females but was only increased by the programme among males. This gendered pattern of effects may explain why we did not see a mediating effect of the cash transfer through schooling, despite schooling's protective effects against early sexual debut. Results also suggest that cash transfer programmes in Africa can contribute to the reduction of HIV related risk behaviours. PMID- 26853952 TI - Comparison of Outcomes of Patients With Sepsis With Versus Without Acute Myocardial Infarction and Comparison of Invasive Versus Noninvasive Management of the Patients With Infarction. AB - Patients hospitalized with sepsis may be predisposed to acute myocardial infarction (AMI). The incidence, treatment, and outcomes of AMI in sepsis have not been studied. We analyzed data from the National Inpatient Sample from 2002 to 2011 for patients with a diagnosis of sepsis. The incidence of AMI as a nonprimary diagnosis was evaluated. Propensity score matching was used to identify a cohort of patients with secondary AMI and sepsis with similar baseline characteristics who were managed invasively (defined as cardiac catheterization, percutaneous coronary intervention [PCI], or coronary artery bypass graft [CABG] surgery) or conservatively. The primary outcome was in-hospital all-cause mortality. A total of 2,602,854 patients had a diagnosis of sepsis. AMI was diagnosed in 118,183 patients (4.5%), the majority with non-ST elevation AMI (71.4%). In-hospital mortality was higher in patients with AMI and sepsis than those with sepsis alone (35.8% vs 16.8%, p <0.0001; adjusted odds ratio 1.24, 95% CI 1.22 to 1.26). In patients with AMI, 11,899 patients (10.1%) underwent an invasive management strategy, in which 4,668 patients (39.2%) underwent revascularization. PCI was performed in 3,413 patients (73.1%), CABG in 1,165 (25.0%), and both CABG and PCI in 90 patients (1.9%). In a propensity-matched cohort of 23,708 patients with AMI, invasive management was associated with a lower mortality than conservative management (19.0% vs 33.4%, p <0.001; odds ratio 0.47, 95% CI 0.44 to 0.50). In subgroups that underwent revascularization, the odds of mortality were consistently lower than corresponding matched subjects from the conservative group. In conclusion, myocardial infarction not infrequently complicates sepsis and is associated with a significant increase in in-hospital mortality. Patients managed invasively had a lower mortality than those managed conservatively. PMID- 26853953 TI - Influence of Total Coronary Occlusion on Clinical Outcomes (from the Bypass Angioplasty Revascularization Investigation 2 DiabetesTrial). AB - Our aim was to evaluate the influence of chronic total occlusions (CTOs) on long term clinical outcomes of patients with coronary heart disease and diabetes mellitus. We evaluated patients with coronary heart disease and diabetes mellitus enrolled in the Bypass Angioplasty Revascularization Investigation 2 Diabetes, who underwent either prompt revascularization (PR) with intensive medical therapy (IMT) or IMT alone according to the presence or absence of CTO. Of 2,368 patients enrolled in the trial, 972 patients (41%) had CTO of coronary arteries. Of those, 482 (41%) and 490 (41%) were in the PR with IMT versus IMT only groups, respectively. In the PR group, patients with CTO were more likely to be selected for the coronary artery bypass grafting stratum (coronary artery bypass grafting 62% vs percutaneous coronary intervention 31%, p <0.001). Compared to the non-CTO group, patients with CTO had more abnormal Q wave, abnormal ST depression, and abnormal T waves. The myocardial jeopardy score was higher in the CTO versus non CTO group (52 [36 to 69] vs 37 [21 to 53], p <0.001). After adjustment, 5-year mortality rate was significantly higher in the CTO group in the entire cohort (hazard ratio [HR] 1.35, p = 0.013) and in patients with CTO managed with IMT (HR 1.46, p = 0.031). However, the adjusted risk of death was not increased in patients managed with PR (HR 1.26, p = 0.180). In conclusion, CTO of coronary arteries is associated with increased mortality in patients treated medically. However, the presence of a CTO may not increase mortality in patients treated with revascularization. Larger randomized trials are needed to evaluate the effects of revascularization on long-term survival in patients with CTO. PMID- 26853954 TI - Impact of Physical Inactivity on Mortality in Patients With Heart Failure. AB - The impact of physical inactivity on heart failure (HF) mortality is unclear. We analyzed data from the HF Adherence and Retention Trial (HART) which enrolled 902 patients with New York Heart Association class II/III HF, with preserved or reduced ejection fraction, who were followed for 36 months. On the basis of mean self-reported weekly exercise duration, patients were classified into inactive (0 min/week) and active (>=1 min/week) groups and then propensity score matched according to 34 baseline covariates in 1:2 ratio. Sedentary activity was determined according to self-reported daily television screen time (<2, 2 to 4, >4 h/day). The primary outcome was all-cause death. Secondary outcomes were cardiac death and HF hospitalization. There were 196 inactive patients, of whom 171 were propensity matched to 342 active patients. Physical inactivity was associated with greater risk of all-cause death (hazard ratio [HR] 2.01, confidence interval [CI] 1.47 to 3.00; p <0.001) and cardiac death (HR 2.01, CI 1.28 to 3.17; p = 0.002) but no significant difference in HF hospitalization (p = 0.548). Modest exercise (1 to 89 min/week) was associated with a significant reduction in the rate of death (p = 0.003) and cardiac death (p = 0.050). Independent of exercise duration and baseline covariates, television screen time (>4 vs <2 h/day) was associated with all-cause death (HR 1.65, CI 1.10 to 2.48; p = 0.016; incremental chi-square = 6.05; p = 0.049). In conclusion, in patients with symptomatic chronic HF, physical inactivity is associated with higher all cause and cardiac mortality. Failure to exercise and television screen time are additive in their effects on mortality. Even modest exercise was associated with survival benefit. PMID- 26853955 TI - Amiodarone-Induced Thyrotoxicosis Recurrence After Amiodarone Reintroduction. AB - Reintroduction of amiodarone in patients with a history of amiodarone-induced thyrotoxicosis (AIT) is rarely used. To date, the risk of AIT recurrence after amiodarone reintroduction is unpredicted. The aim of the study was to evaluate the risk of AIT recurrence. Retrospectively, from 2000 to 2011, all euthyroid patients with a history of AIT with amiodarone reintroduction were included. Type and severity of the first AIT, amiodarone chronology, and thyroid function evolution after reintroduction of amiodarone were investigated: 46 of 172 patients with AIT history needed amiodarone reintroduction. At first AIT episode, the mean age was 62.2 +/- 16 years with male gender predominance; 65% of patients were classified as type 1 AIT. AIT recurred in 14 patients (30%), 12 patients developed hypothyroidism (26%), and 20 patients remained euthyroid (44%). Characteristics of type 1 AIT during the first episode, namely briefer exposure period to amiodarone and longer duration of treatment to normalize thyroid hormones, were predictive of AIT recurrence; 73% of patients (8 of 11) with previous episode of type 1 AIT, who did not receive a preventive thioamide treatment, developed a second episode of AIT. Thioamide preventive treatment could be useful to prevent type 1 AIT recurrence. In conclusion, AIT recurrence after amiodarone reintroduction is 4 times more frequent in patients with type 1 AIT history. Thyroid ablation before amiodarone reintroduction in patients with a history of type 1 AIT is preferred. Preventive thioamide treatment could be suggested in patients with type 1 AIT history pending for surgery. PMID- 26853956 TI - New Studies on Hallucinogenic Mushrooms: History, Diversity, and Applications in Psychiatry. AB - This paper is a review of the new studies or new explanations of the hallucinogenic mushrooms, regarding their diversity, history, traditions, and problems in their recreational use, new taxonomic studies, and their modern applications in medicine, all of them since the 1970s to the present. PMID- 26853957 TI - Consequences of Misnomer or Mistakes in Identification of Fungal Species. AB - The author, as a reviewer of many international journals, describes his long standing experiences with incorrect identification of mushroom and fungal species and the resultant incorrect naming of those species that served as experimental models. From his own praxis, he selected several characteristic examples that sometimes ended in a curious situation. Some recommendations to authors of publications and persons responsible for the proper naming of mushrooms under study are summarized. PMID- 26853958 TI - Isolation and Characterization of a Ubiquitin-Like Ribonuclease from the Cultured Deep Root Mushroom, Oudemansiella radicata (Higher Basidiomycetes). AB - The isolation of a novel 13.5-kDa ribonuclease, displaying a ubiquitin-like inner peptide sequence, from dried fruiting bodies of the cultured mushroom Oudemansiella radicata (Relhan: Fr.) Singer (=Xerula radicata) is reported. The purification protocol deployed encompassed sequentially, cation/anion exchange chromatography on CM-cellulose, DEAE-cellulose and SP-Sepharose, and FPLC-gel filtration on a Superdex 75 column. The purified enzyme manifested optimum activity at 70 degrees C and pH 4.6, respectively. The activity of the RNase was inhibited by the majority of metal ions tested, especially Al3+, Hg2+, and Cd2+ ions, but was promoted by K+ ions. It exhibited the highest ribonucleolytic activity toward poly (C), lower activity toward poly (G), and negligible activity toward poly (U) and poly (A). Compared with mushroom ubiquitin-like RNases reported earlier, O. radicata RNase possesses a larger molecular mass, distinctive chromatographic behavior on DEAE-cellulose, a lower optimum pH, and a unique polyhomoribonucleotide specificity. PMID- 26853959 TI - Lion's Mane, Hericium erinaceus and Tiger Milk, Lignosus rhinocerotis (Higher Basidiomycetes) Medicinal Mushrooms Stimulate Neurite Outgrowth in Dissociated Cells of Brain, Spinal Cord, and Retina: An In Vitro Study. AB - Neurodegenerative disease is defined as a deterioration of the nervous system in the intellectual and cognitive capabilities. Statistics show that more than 80-90 million individuals age 65 and above in 2050 may be affected by neurodegenerative conditions like Alzheimer's and Parkinson's disease. Studies have shown that out of 2000 different types of edible and/or medicinal mushrooms, only a few countable mushrooms have been selected until now for neurohealth activity. Hericium erinaceus is one of the well-established medicinal mushrooms for neuronal health. It has been documented for its regenerative capability in peripheral nerve. Another mushroom used as traditional medicine is Lignosus rhinocerotis, which has been used for various illnesses. It has been documented for its neurite outgrowth potential in PC12 cells. Based on the regenerative capabilities of both the mushrooms, priority was given to select them for our study. The aim of this study was to investigate the potential of H. erinaceus and L. rhinocerotis to stimulate neurite outgrowth in dissociated cells of brain, spinal cord, and retina from chick embryo when compared to brain derived neurotrophic factor (BDNF). Neurite outgrowth activity was confirmed by the immu nofluorescence method in all tissue samples. Treatment with different concentrations of extracts resulted in neuronal differentiation and neuronal elongation. H. erinaceus extract at 50 ug/mL triggered neurite outgrowth at 20.47%, 22.47%, and 21.70% in brain, spinal cord, and retinal cells. L. rhinocerotis sclerotium extract at 50 ug/mL induced maximum neurite outgrowth of 20.77% and 24.73% in brain and spinal cord, whereas 20.77% of neurite outgrowth was observed in retinal cells at 25 ug/mL, respectively. PMID- 26853960 TI - Anti-Gastric Ulcer Activity of Polysaccharide Fraction Isolated from Mycelium Culture of Lion's Mane Medicinal Mushroom, Hericium erinaceus (Higher Basidiomycetes). AB - Hericium erinaceus is a culinary-medicinal mushroom that is used in traditional medicine, in folk medicine, and as medicinal cuisine in Asian countries such as China, Japan, and Korea. H. erinaceus exhibits various pharmacological properties, such as anti-cancer, immunomodulation, anti-dementia, and anti gastric ulcer effects. The extracts of the fruiting body of H. erinaceus demonstrate anti-gastritis activity. However, the active principle in the extract, as well as the mechanism to treat gastric ulcers, remains uncertain. The current study aims to identify the active component, with anti-gastric ulcer function, from the extracts of the H. erinaceus mycelium culture. In the experiment, anti-gastric ulcer activity was evaluated using an ethanol-induced ulcer model in mice and with an 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyltetrazolium bromide assay using MC cell lines. The results suggest that the polysaccharide fraction can significantly decrease the ulcerated area compared with the control group and the effect is fairly dose dependent, irrespective of animal or cell experiments. These results indicate that the polysaccharide fraction is the active component of the H. erinaceus mycelium culture, which protects against gastric ulcers. PMID- 26853961 TI - Medicinal Mushroom Cracked-Cap Polypore, Phellinus rimosus (Higher Basidiomycetes) Attenuates Acute Ethanol-Induced Lipid Peroxidation in Mice. AB - Alcohol abuse and alcoholism remain one of the major health issues worldwide, especially in developing countries. The protective effect of Phellinus rimosus against acute alcohol-induced lipid peroxidation in the liver, kidney, and brain as well as its effect against antioxidant enzyme activity such as superoxide (SOD) and catalase (CAT) in the liver was evaluated in mice. Ethyl acetate extract of Ph. Rimosus (50 mg/kg body wt, p.o.) 1 h before each administration of alcohol (3 mL/kg, p.o.; total 2 doses at 24-h intervals) protected against lipid peroxidation in all organs and attenuated the decline of SOD and CAT activity in the liver. The fold increase in lipid peroxidation, including conjugated diene and thiobarbituric acid reactive substance (TBARS) levels, was highest in the liver. There were 2.6- and 1.5- fold increases in TBARS levels in the liver of the alcohol alone- and alcohol+Ph. Rimosus-treated groups, compared with that of the normal group. Activity of SOD and CAT in the liver of alcohol- and alcohol+Ph. Rimosus- treated animals was 9.05+/-1.38, 18.76+/-1.71, and 11.26+/ 1.02, 31.58+/-3.35 IU/mg protein, respectively. Extract at 1 mg/mL inhibited 50.6% activity of aniline hydroxylase (CYP2E1) in liver homogenate. From these results, we concluded that the extract significantly protected against the lipid peroxidation. Protection in the liver may be due to the inhibitory effect on CYP2E1 as well as the direct radical scavenging effect of Ph. Rimosus, which warrants further research. PMID- 26853962 TI - Hepatoprotective Activity of Water Extracts from Chaga Medicinal Mushroom, Inonotus obliquus (Higher Basidiomycetes) Against Tert-Butyl Hydroperoxide Induced Oxidative Liver Injury in Primary Cultured Rat Hepatocytes. AB - We examined the hepatoprotective activity of Inonotus obliquus water extract (IO W) against tert-butyl hydroperoxide (t-BHP)-induced oxidative liver injury in the primary cultured rat hepatocyte. The 50% radical scavenging concentrations (SC50s) of IO-W for radical-scavenging activity against 2,2'-azino-bis-(3 ethylbenzothi- azoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picryl-hydrazyl (DPPH) were 5.19 mg/mL and 0.39 mg/mL, respectively. IO-W pretreatment to the primary cultured hepatocytes significantly (p<0.05) protected the cells from t BHP-induced cytotoxic injury even at a low concentration of IO-W (10 ug/mL). The cellular leakage of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH), as well as malondialdehyde (MDA) formation caused by t-BHP were significantly (p<0.05) suppressed by IO-W pretreatment (>100 ug/ mL). In conclusion, this study demonstrates that IO-W exhibited hepatoprotective activity against t-BHP-induced oxidative liver injury in the primary cultured hepatocyte probably via its abilities of quenching free radicals, inhibiting the leakage of ALT, AST, and LDH, and decreasing MDA formation. PMID- 26853963 TI - Cordyceps s.l. (Ascomycetes) Species Used as Medicinal Mushrooms are Closely Related with Higher Ability to Produce Cordycepin. AB - Cordyceps s.l. (sensu lato) species have been used as herbal medicines; one of their main constituents is cordycepin. As genome sequencing techniques have become more cost-effective and more popular, more entomogenous fungal genomes have been sequenced and published. Here, we constructed a phylogenetic tree based on 18S rRNA sequences from Cordyceps species and analyzed the copy number of the key enzymes involved in biosynthesis of cordycepin from related fungal genomes that have been published. The sequences of the 18S rRNA gene were examined, and seven single nucleotides were found that could represent the evolutionary history of Cordyceps s.l. and which perfectly fit the phylogenetic tree. Their evolution was influenced mainly by host factors, rather than geographical location. The Cordyceps s.l. species that are used as herbal medicines are closely related in the phylogenetic tree. The major species for Chinese pharmaceutical markets, such as C. militaris and C. sinensis, have higher copy numbers of 5'-nucleotidase and adenylate kinase, and ribonucleotide reductases (RNRs), respectively. Moreover, absence of an RNR inhibitor may cause cordycepin accumulation. Presence of an RNR inhibitor may lead to lower cordycepin levels in fungal species in which no medicinal applications have been described. Cordycepin is not only an important secondary metabolite that is used as an herbal medicine, but it also has significance for understanding the evolution of these entomogenous species. PMID- 26853964 TI - Molecular Cloning and Characterization of a Subtilisin-Like Serine Protease Gene (Pr1) from the Medicinal Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes). AB - In the Chinese caterpillar mushroom Ophiocordyceps sinensis, a subtislin-like serine protease (Pr1) is one of the most important enzymes for its infection activity against insect cuticles. The Pr1 gene was isolated from the valuable Chinese medicinal fungus O. sinensis using rapid amplification of 5' and 3' complementary DNA ends. The 2079-bp full-length complementary DNA sequence containing the 1605-bp predicted open reading frame of the Pr1 gene was obtained (GenBank accession no. KF836756). The open reading frame encodes a protein comprising 534 amino acids. Protein sequence multiple alignment analysis revealed high homology with 16 other subtilisin serine proteases and exhibited the highly conserved catalytic domain (D195, H227, and S393). We also constructed a phylogenetic tree in this study. Further molecular studies are needed to elucidate the mechanisms of fungal infection. PMID- 26853965 TI - Optimization of the Yield of Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Higher Basidiomycetes), Cultivated on a Sunflower Seed Hull Substrate Produced in Argentina: Effect of Olive Oil and Copper. AB - Sunflower seed hulls were used as the main component of a solid substrate for the cultivation of the lingzhi or reishi medicinal mushroom Ganoderma lucidum. This study evaluated the effects of supplementing the substrate with olive oil and copper (II) on the mushroom production (MP) parameters and fruiting body total triterpenoid content. The addition of 1.5% olive oil increased total MP by 21.7% (dry basis) in 3 flushes. Copper (60 ppm) increased the daily productivity of the first flush (MP per day) by both reducing the time needed to harvest the crop and increasing the MP. However, the MP at the second and third flushes was reduced. When both supplements were combined, the MP at the first flush was 43% higher than with control treatment. No significant change in mushroom total triterpenoid content was observed by the addition of supplements to the substrate. An increase of 145-155% in the mushroom copper content was obtained by the addition of 60 ppm copper to the substrate. It is thus recommended to use substrate formulations containing both olive oil and copper (II) and harvest just the first flush. PMID- 26853966 TI - Fruiting Body Production of the Medicinal Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes), in Artificial Medium. AB - Ophiocordyceps sinensis (syn. Cordyceps sinensis), regarded as the "Himalayan Viagra", is widely used for medicinal treatment and health foods. The price of O. sinensis has continued to increase over the past few years because of the growing worldwide demand and resource limitations. Artificial cultivation of the fruiting bodies to substitute natural O. sinensis is urgently needed for the effective protection of a valuable bioresource and environment in the Tibetan plateau, and for commercial trade. In this study, the anamorph of 3 isolates was separated from natural O. sinensis and identified by molecular markers as Hirsutella sinensis. These fungal isolates were cultured in a rice-based medium at 9-13 degrees C for 50 days for mycelial growth, at 4 degrees C for 100 days for stromatal induction, and at 13 degrees C for 40 days for fruiting body formation. The mature fruiting bodies with mature perithecium were harvested in about 140 days. This is, to our knowledge, the first report of stable fruiting body production of O. sinensis by artificial media in the low-altitude area outside the Tibetan plateau. PMID- 26853967 TI - Spectral assignments in the infrared absorption region and anomalous thermal hysteresis in the interband electronic transition of vanadium dioxide films. AB - The metal-insulator transition (MIT) is of key importance for understanding the fundamental electronic interaction that determines the physical properties of vanadium dioxide (VO2) film. Here, the spectral slopes of transmittance and reflectance in the infrared absorption region (about 0.62-1.63 eV) and the interband electronic transitions for VO2 films with thicknesses of 27, 40 and 63 nm have been investigated. The potential applications of the spectral slopes were presented in detail. It is found that the variation of resistivity and transmittance increases with the spectral slopes of transmittance and reflectance. It is surprising that the resistivity of the VO2 film with a thickness of 27 nm is larger than that of the VO2 film with a thickness of 40 nm in the metal state. In addition, an anomalous counterclockwise thermal hysteresis with higher energy from the interband electronic transition was also found during the MIT process for the thinnest film. It is believed that this remarkable phenomenon could be related to the correlation effects in the rutile phase, which could lead to the splitting of the a1g band into Hubbard bands. The lower Hubbard band would result in an electronic transition blue-shift with the empty e band, which can explain the origin of the counterclockwise thermal hysteresis and the abnormal resistivity in the metal state. PMID- 26853968 TI - The Volume-metabolic Combined Parameters from (18)F-FDG PET/CT May Help Predict the Outcomes of Cervical Carcinoma. AB - RATIONALE AND OBJECTIVES: The aim of this study was to evaluate the prognostic value of 18-fluoro-2-deoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) volume-metabolic combined parameters in patients with cervical carcinoma. MATERIALS AND METHODS: We retrospectively reviewed 91 consecutive patients' whole-body FDG-PET/CT images, and further measured and calculated FDG PET/CT volume-metabolic parameters, including cervical metabolic tumor volume (CMTV), cervical total lesion glycolysis (CTLG), whole-body metabolic tumor volume (WB-MTV), whole-body total lesions glycolysis (WB-TLG). The prognostic value of these tumor volume-metabolic measures was assessed by Cox Proportional Hazard Regression Analysis. RESULTS: The overall survival (OS) was 88.8% for patients with low CMTV (<=53.75 mL) and 45.5% for those with high CMTV (>53.75 mL), respectively (P < 0.01, 95% confidence interval). Univariate analysis showed that CMTV and CTLG were significant prognostic factors for OS, in addition to International Federation of Gynecology and Obstetrics (FIGO) stage, age, lymphadenopathy, and maximum standardized uptake value (SUVmax) (P < 0.05 for all). On multivariate analysis, CMTV remained significant for OS, in addition to FIGO stage (P < 0.05 for all). CMTV remains as prognostic factor for OS regardless of patients' FIGO stages (P < 0.05). In patients in the metastatic diseases group, univariate and multivariate analyses demonstrated that CMTV, WB MTV, and WB-TLG were independent prognostic factors for OS (P < 0.05 for all). CONCLUSION: CMTV, WB-MTV, and WB-TLG are reliable prognostic factors for patients with cervical carcinoma and should be included in FDG-PET/CT reports to guide referral clinicians for risk-adapted therapies. PMID- 26853969 TI - Semiautomated Global Quantification of Left Ventricular Myocardial Perfusion at Stress Dynamic CT:: Diagnostic Accuracy for Detection of Territorial Myocardial Perfusion Deficits Compared to Visual Assessment. AB - RATIONALE AND OBJECTIVES: To evaluate the diagnostic accuracy of semiautomated global quantification of left ventricular myocardial perfusion derived from stress dynamic computed tomography myocardial perfusion imaging (CTMPI) for detection of territorial perfusion deficits (PD). MATERIALS AND METHODS: Dynamic CTMPI datasets of 71 patients were analyzed using semiautomated volume-based software to calculate global myocardial blood flow (MBF), myocardial blood volume, and volume transfer constant. Optimal cutoff values to assess the diagnostic accuracy of these parameters for detection of one- to three-vessel territories with PD in comparison to visual analysis were calculated. RESULTS: Nonsignificant differences (P = 0.694) were found for average global MBF in patients without PD and single-territorial PD. Significant differences were found for mean global MBF in patients with PD in two (P < 0.0058) and three territories (P < 0.0003). Calculated optimal thresholds for global MBF and myocardial blood volume resulted in a sensitivity, specificity, and negative predictive value of 100% for detection of three-vessel territory PD. For detection of >=2 territories with PD, global MBF was superior to other parameters (sensitivity 81.3%, specificity 90.9%, and negative predictive value 94.3%). CONCLUSIONS: Semiautomated global quantification of left ventricular MBF during stress dynamic CTMPI shows high diagnostic accuracy for detection of >=2 vessel territories with PD, facilitating identification of patients with multi-territorial myocardial PD. PMID- 26853970 TI - Feasibility of Respiratory-gated High-pitch Spiral CT:: Free-breathing Inspiratory Image Quality. AB - RATIONALE AND OBJECTIVES: This study aimed to develop and implement a respiratory gated setup for dual-source computed tomography (CT) at high pitch to examine patients in a reproducible inspiratory phase. MATERIALS AND METHODS: Twenty-one patients underwent free-breathing respiratory-gated chest CT using a high-pitch scan mode no more than 6 months after inspiratory breath-held nongated CT, which serves as reference. Scan parameters were as follows: pitch = 3.4, 128 * 0.6 mm collimation, 0.28 s gantry rotation time, and 150 ref.mAs per tube at 120 kV. The examinations were triggered using the tidal wave provided by a respiratory-gating system as input signal. Image quality was assessed focusing on artifacts and delineation of the anatomical and pathological structures. Lung volumes were measured on both free-breathing and reference examinations. RESULTS: All examinations were performed without complications. Image quality was high with both protocols. Significantly less motion artifacts were recorded with the high pitch mode compared to the reference (P = 0.02). Most of the artifacts were located in the peripheral parts of the lower lobes for the study group and in the central part of the left lower lobe for the reference. Average total lung volume was 4.5 +/- 1.5 L in respiratory-gated examinations and 5.8 +/- 0.9 L in examinations with breath-hold in inspiration. CONCLUSIONS: High-pitch chest CT scanning during free breathing minimizes motion artifacts, improving image quality in patients with limited breath-holding abilities. To assure scanning in an inspiratory phase, data acquisition should be triggered with a respiratory gating system. PMID- 26853971 TI - Discrimination between Metastatic and Nonmetastatic Mesorectal Lymph Nodes in Rectal Cancer Using Intravoxel Incoherent Motion Diffusion-weighted Magnetic Resonance Imaging. AB - RATIONALE AND OBJECTIVES: The aim of the study was to investigate the diagnostic value of intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM DWI) for discriminating nonmetastatic from metastatic mesorectal lymph nodes in rectal cancer. MATERIALS AND METHODS: IVIM DWI was performed preoperatively on 50 patients with rectal carcinoma. The short-axis diameter, short- to long-axis diameter ratio, and IVIM-based parameter (pure diffusion coefficient [D], pseudo-diffusion coefficient [D*] and perfusion fraction [f]) values were compared between the metastatic and nonmetastatic lymph node groups. RESULTS: The short-axis diameter; short- to long-axis diameter ratio; and D, D*, and f values for the nonmetastatic lymph node group (n = 28) were 6.446 +/- 1.201 mm, 0.815 +/- 0.099, 1.071 +/- 0.234 * 10(-3) mm(2)/s, 15.443 +/- 5.946 mm(2)/s and 0.261 +/- 0.128, respectively, and were 9.045 +/- 3.185 mm, 0.809 +/- 0.099, 0.816 +/- 0.121 * 10(-3) mm(2)/s, 11.679 +/- 7.521 * 10(-3) mm(2)/s, and 0.190 +/ 0.064, respectively, for the metastatic lymph node group (n = 31). The short axis diameter for the metastatic group was significantly higher than for the nonmetastatic group (P <0.001). The metastatic group exhibited significantly lower D and D* values than the nonmetastatic group (P <0.01). The short- to long axis diameter ratio and f values did not differ significantly between the two groups. Optimal cutoff values (area under the curve, sensitivity, and specificity) for distinguishing metastatic from nonmetastatic lymph nodes were as follows: short-axis diameter = 5.563 mm (0.783, 74.2%, 82.1%); D = 0.667 * 10(-3) mm(2)/s (0.885, 77.4%, 89.3%); and D* = 0.485 * 10(-3) mm(2)/s (0.727, 80.6%, 67.9%). CONCLUSION: IVIM DWI is useful to differentiate between metastatic and nonmetastatic mesorectal lymph nodes in rectal cancer. PMID- 26853972 TI - A pilot study of patient-specific cardiovascular MDCT dose maps and their utility in estimating patient-specific organ and effective doses in obese patients. AB - BACKGROUND: Estimates of effective dose (E) for cardiovascular CT are obtained from a scanner-provided dose metric, the dose-length product (DLP), and a conversion factor. These estimates may not adequately represent the risk of a specific scan to obese adults. OBJECTIVE: Our objective was to create dose maps sensitive to patient size and anatomy in the irradiated region from a patient's own CT images and compare measured E (EDoseMap) to doses determined from standard DLP conversion (EDLP) in obese adults. METHODS: 21 obese patients (mean body mass index, 39 kg/m(2)) underwent CT of the pulmonary veins, thoracic aorta, or coronary arteries. DLP values were converted to E. A Monte Carlo tool was used to simulate X-ray photon interaction with virtual phantoms created from each patient's image set. Organ doses were determined from dose maps. EDoseMap was computed as a weighted sum of organ doses multiplied by tissue-weighting factors. RESULTS: EDLP (mean +/- SD, 5.7 +/- 3.3 mSv) was larger than EDoseMap (3.4 +/- 2.4 mSv) (difference = 2.3; P < .001). CONCLUSION: Dose maps derived from patient CT images yielded lower effective doses than DLP conversion methods. Considering over all patient size, organ size, and tissue composition could lead to better dose metrics for obese patients. PMID- 26853973 TI - Raman Spectroscopic Characterization of Packaged L. pneumophila Strains Expelled by T. thermophila. AB - The intracellular lifestyle of L. pneumophila within protozoa is considered to be a fundamental process that supports its survival in nature. However, after ingesting the cells of L. pneumophila, some protozoa expel them as compressed live cells in the form of small rounded pellets. The pellets of tightly packaged viable but not culturable forms (VBNCFs) as well as highly infectious mature intracellular forms (MIFs) of L. pneumophila are considered as infectious particles most likely capable to cause human infection. Since L. pneumophila cells are hardly culturable from these pellets, detection methods for packaged live L. pneumophila forms remaining in water should be cultivation free. Hence, we demonstrate the potential of Raman microspectroscopy to directly sort pellets containing L. pneumophila cells, expelled by T. thermophila, and to characterize them on the basis of their Raman spectra. PMID- 26853974 TI - Age-related changes in molar topography and shearing crest length in a wild population of mountain Gorillas from Volcanoes National Park, Rwanda. AB - OBJECTIVES: Great ape teeth must remain functional over long lifespans. The molars of the most folivorous apes, the mountain gorillas, must maintain shearing function for 40+ years while the animals consume large quantities of mechanically challenging foods. While other folivorous primates experience dental senescence, which compromises their occlusal surfaces and affects their reproductive success as they age, it is unknown whether dental senescence also occurs in mountain gorillas. In this article, we quantified and evaluated how mountain gorilla molars change throughout their long lifespans. MATERIALS AND METHODS: We collected high-resolution replicas of M(1)s (n = 15), M(2)s (n = 13), and M(3)s (n = 11) from a cross-sectional sample of wild mountain gorilla skeletons from the Virunga Volcanoes, ranging in age from 4 to 43 years. We employed dental topographic analyses to track how aspects of occlusal slope, angularity, relief index, and orientation patch count rotated change with age. In addition, we measured the relative length of shearing crests in two- and three-dimensions. RESULTS: Occlusal topography was found to decrease, while 2D relative shearing crest length increased, and 3D relative crest lengths were maintained with age. DISCUSSION: Our findings indicate that shearing function is maintained throughout the long lifetimes of mountain gorillas. Unlike the dental senescence experienced by other folivorous primates, mountain gorillas do not appear to possess senesced molars despite their long lifetimes, mechanically challenging diets, and decreases in occlusal topography with age. PMID- 26853975 TI - Unwinding the Novel Genes Involved in the Differentiation of Embryonic Stem Cells into Insulin-Producing Cells: A Network-Based Approach. AB - Diabetes is one of the main causes of death in the world. Diabetes is marked by high blood glucose levels and develops when the body doesn't produce enough insulin or is not able to use insulin effectively, or both. Type I diabetes is a chronic sickness caused by lack of insulin due to the autoimmune destruction of pancreatic insulin-producing beta cells. Research on permanent cure for diabetes is in progress with several remarkable findings in the past few decades among which stem cell therapy has turned out to be a promising way to cure diabetes. Stem cells have the remarkable potential to differentiate into glucose-responsive beta cells through controlled differentiation protocols. Discovering novel targets that could potentially influence the differentiation to specific cell type will help in disease therapy. The present work focuses on finding novel genes or transcription factors involved in the human embryonic stem cell differentiation into insulin-producing beta cells using network biology approach. The interactome of 321 genes and their associated molecules involved in human embryonic stem cell differentiation into beta cells was constructed, which includes 1937 nodes and 8105 edges with a scale-free topology. Pathway analysis for the hubs obtained through MCODE revealed that four highly interactive hubs were relevant to embryonic stem cell differentiation into insulin-producing cells. Their role in different pathways and stem cell differentiation was studied. Centrality parameters were applied to identify the potential controllers of the differentiation processes: BMP4, SALL4, ZIC1, NTS, RNF2, FOXO1, AKT1 and GATA4. This type of approach gives an insight to identify potential genes/transcription factors which may play influential role in many complex biological processes. PMID- 26853976 TI - Enantioselective assembly of amphipathic chiral polymer and racemic chiral small molecules during preparation of micro-scale polymer vesicles. AB - Enantioselective assembly is observed during preparation of vesicles from a solution mixture of an amphipathic block copolymer bearing pendent chiral L- or D phenylalanine groups in hydrophobic segments and racemic chiral small molecules. Primary experimental results reveal that racemic chiral small molecules have been enantioselectively encapsulated into the hydrophobic shells of assembled vesicles with homochiral bilayer membrane structure, showing reverse CD signals compared with the original vesicles. A further study shows that the enantiomeric excess obtained through the enantioselective assembly is directly dependent on the molecular weight of the hydrophobic chiral chain segments, implying both the hydrophobic interaction and chirality are key points during the assembly of vesicles. Other factors, such as hydrogen-bonding interactions and pi-pi stacking interaction, are also found to be responsible for the enantioselective assembly phenomenon during the formation of the vesicles. PMID- 26853978 TI - Editorial: Small Molecule Drug Discovery for Pediatric Diseases. PMID- 26853977 TI - Acute paraquat exposure impairs colonic motility by selectively attenuating nitrergic signalling in the mouse. AB - Paraquat, a common herbicide, is responsible for large numbers of deaths worldwide through both deliberate and accidental ingestion. Previous studies have eluded that the bioavailability of paraquat increases substantially with increasing dose and that these changes may in part be due to the effects that these high concentrations have on the gastrointestinal tract (GI tract). To date, the actions of acute, high concentrations (20mM for 60 min) of paraquat on the GI tract, particularly the colon which is a major site of paraquat absorption, are unknown. This study examined the effects of acute paraquat administration on colonic motility in the C57BL/6 mouse. Acute paraquat exposure decreased colonic motility and the amplitude of colonic migrating motor complexes (CMMCs), which are major motor patterns involved in faecal pellet propulsion. In isolated segments of distal colon, paraquat increased resting tension and markedly attenuated electrical field stimulation-evoked relaxations. Pharmacological dissection of paraquat's mechanism of action on both the CMMCs and field stimulated tissue using the nitric oxide synthase inhibitor NG-nitro-L-arginine and direct measurement of NO release from the myenteric plexus, demonstrated that paraquat selectively attenuates nitrergic signalling pathways. These changes did not appear to be due to alterations in colonic oxidative stress, inflammation or complex 1 activity, but were most likely caused by paraquat's ability to act as a redox couple. In summary, these data demonstrate that acute paraquat exposure attenuates colonic transit. These changes may facilitate the absorption of paraquat into the circulation and so facilitate its toxicity. PMID- 26853979 TI - Distal anastomosis patterns of the descending branch of the lateral circumflex femoral artery. AB - BACKGROUND: The reverse anterolateral thigh (ALT) flap has shown good results in the treatment of patients who have skin and soft tissue defects around the knee and shin. The objective of this study was to show the anastomotic patterns of the descending branch of lateral femoral circumflex artery (db-LCFA) and locate the appropriate pivot point for reverse ALT flap. MATERIALS AND METHODS: Fifty thighs from 25 embalmed cadavers from the Anatomy Department, Khon Kaen University in 2012, were dissected. The patterns of distal anastomoses of db-LCFA were recorded and appropriate pivot points for the reverse ALT flap were measured. RESULTS: Three patterns of distal anastomosis of the db-LCFA were identified, including the anastomoses to the superolateral genicular arteries (46%), anastomoses to the profunda femoral arteries (28%), and unidentified distal anastomoses (26%). The mean distance of the pivot point was 9.4 +/- 3.7 cm from the lateral epicondyle. The mean pedicular length was 13.2 +/- 5.4 cm (mean +/- SD). Most cadavers, 76%, showed a single db-LCFA. In cases where there was more than one db-LCFA, the distal anastomoses were found to be originating from the most medial db-LCFA. CONCLUSION: The reverse ALT flap technique showed good results in the treatment of patients with skin and soft tissue defects around the knee and shin. Variations of the anastomoses and branching patterns of the db-LCFA may influence flap survival. Additional preoperative vascular evaluations would be helpful in defining the most compatible area from which to harvest the flap. PMID- 26853980 TI - [Frontiers of endoscopic diagnosis for cancer -innovation of a novel endoscopy]. PMID- 26853981 TI - [Current status and issues of the diagnosis of superficial esophageal cancer using image-enhanced magnifying endoscopy]. PMID- 26853982 TI - [The endoscopic diagnosis of early gastric cancer using advanced diagnostic endoscopy]. PMID- 26853983 TI - [Advanced diagnostic endoscopy for gastric cancers discovered after H. pylori eradication]. PMID- 26853984 TI - [A case of gastrointestinal amyloidosis and hypoproteinemia improved by tocilizumab]. AB - A woman in her 70s presented with dehydration and malnutrition due to watery diarrhea. She was examined and diagnosed with gastrointestinal amyloidosis accompanied by a protein-losing gastroenteropathy secondary to rheumatoid arthritis. She first underwent treatment with an anti-tumor necrosis factor alpha (TNF-alpha) antibody for secondary amyloidosis, but due to lack of adequate response, she was switched to an anti-interleukin (IL)-6 receptor antibody. Her clinical symptoms subsequently improved, and endoscopy revealed a marked decrease of amyloid protein deposits in the digestive tract. She was followed up for 3 years while continuing to receive the anti-IL-6 receptor antibody, with no recurrence. Although secondary amyloidosis is a fatal disease associated with chronic inflammatory diseases, clinical symptoms and prognosis have recently been improved by intervention with biological therapies. In particular, anti-IL-6 receptor antibodies have been reported to be superior to anti-TNF-alpha antibodies in the treatment of secondary amyloidosis and are expected to play a central role in treating secondary amyloidosis in the future. PMID- 26853985 TI - [Squamous cell carcinoma of the anal canal treated with chemoradiotherapy in a patient with HIV]. AB - Since the introduction of combination antiretroviral therapy (ART), the life expectancy has increased for patients infected with human immunodeficiency virus (HIV). This has been associated with reductions in the incidences of some AIDS defining malignancies, such as Kaposi sarcoma and non-Hodgkin lymphoma, but has coincided with an increased incidence of non-AIDS-defining malignancies, such as anal cancer. However, anal cancers are rare in patients with HIV in Japan. We report the case of an HIV-infected patient with anal cancer treated with chemoradiotherapy. A 37-year-old man receiving ART for HIV infection presented with a 1-month history of left inguinal lymphadenopathy and anal pain. Magnetic resonance imaging and computed tomography revealed a 56-mm mass, left inguinal lymphadenopathy, and left external iliac lymphadenopathy. The mass had infiltrated from the anal canal to the right levator ani and corpus spongiosum. Colonoscopy revealed a tumor with an ulcer in the anal canal. Histological examination of the tumor biopsy specimens confirmed the diagnosis of squamous cell carcinoma. The patient was diagnosed with anal cancer (T4N2M1 stage IV), and he received 5-fluorouracil (1000mg/m(2) on days 1-4 and 29-32) plus mitomycin C (10mg/m(2) on days 1 and 29) and concurrent radiotherapy (total dose, 59.4Gy in 33 fractions) along with ART. The treatment-related adverse events were grade 4 leukopenia and neutropenia, grade 3 thrombocytopenia, and grade 2 radiation dermatitis. Moreover, CD4 suppression was observed:the CD4 count decreased from 190 cells/MUl before chemoradiotherapy to 138 cells/MUl after 3 months, but increased to 210 cells/MUl after 1 year. Because of the grade 4 leukopenia and neutropenia, the dose of 5-fluorouracil was reduced to 800mg/m(2) on days 29-32. A complete response was confirmed on magnetic resonance imaging, and colonoscopy confirmed the disappearance of the anal cancer. The patient is living with no signs of recurrence at 2 years after chemoradiotherapy. When treating HIV infected patients with anal cancer by chemoradiotherapy and ART, clinicians should be aware of the possibility of CD4 suppression. PMID- 26853986 TI - [Detection of early gastric cancer facilitated by surveillance for a pyogenic liver abscess caused by Streptococcus intermedius]. AB - We report a case of early gastric cancer that was detected during surveillance of a pyogenic liver abscess caused by Streptococcus intermedius, an oral microbiota. Treatment with proton pump inhibitors can result in the alteration of gastric bacterial flora by altering intragastric acidity. This can place immunocompromised patients, such as those with diabetes mellitus and the elderly, at an increased risk for disease of the upper gastrointestinal tract to be a route of bacterial transmission. In this case, the patient developed a pyogenic liver abscess. PMID- 26853987 TI - [A case of hemorrhagic cholecystitis associated with Churg-Strauss syndrome]. AB - A woman in her 70s with Churg-Strauss syndrome presented with epigastric pain. She was being treated with steroids at the time of admission. Computed tomography showed swelling of the gallbladder, and percutaneous transhepatic cholangiography revealed bloody secretion. On duodenoscopy, bleeding was observed from the orifice of the major duodenal papilla. Emergency cholecystectomy was performed under a diagnosis of hemorrhagic cholecystitis;intraoperatively, extensive hematoma was detected in the thickened wall of the gallbladder. Subsequent histopathological examination revealed mucosal ulceration with infiltration of inflammatory cells, torn small vessels, and extensive transmural bleeding and abscess formation in the thickened wall of the gallbladder. We considered that the hemorrhagic cholecystitis was induced by either vasculitis or corticosteroid therapy. To the best of our knowledge, this is the first report of hemorrhagic cholecystitis associated with Churg-Strauss syndrome. PMID- 26853988 TI - [Four cases of ceftriaxone-associated biliary pseudolithiasis]. AB - We report four cases of ceftriaxone-associated biliary pseudolithiasis. All cases were treated conservatively without cholecystectomy or endoscopic retrograde cholangiopancreatography. Because conservative treatment is the preferred treatment, clinicians should be aware that biliary pseudolithiasis is possible in patients who have abdominal pain associated with gallbladder stones on imaging. Regardless of whether we are treating adults or children, it is necessary to check for a history of ceftriaxone treatment before symptom onset. PMID- 26853989 TI - [Acute obstructive suppurative pancreatic ductitis after endoscopic retrograde cholangiopancreatography in a patient with carcinoma of the pancreatic head:a case report]. AB - An 85-year-old woman with jaundice was referred to our hospital where she was diagnosed with obstructive jaundice due to carcinoma of the pancreatic head based on blood tests and abdominal computed tomography (CT). We performed endoscopic retrograde cholangiopancreatography (ERCP) for biliary drainage, but 5 days after the procedure, she complained of epigastric pain. Laboratory data revealed an elevated white blood cell count and a high serum amylase concentration. Follow-up CT 6 days after the ERCP revealed that the main pancreatic duct diameter had increased since the time of admission. Therefore, ERCP was performed for pancreatic ductal drainage. Purulent pancreatic juice was drained by endoscopic placement of a nasopancreatic drainage tube in the main pancreatic duct, resulting in marked alleviation of clinical symptoms;however, after removal of the tube, the abdominal pain recurred. Subsequent endoscopic placement of a pancreatic stent improved her clinical status once again. Herein, we report this rare case of acute obstructive suppurative pancreatic ductitis in a patient with carcinoma of the pancreatic head. PMID- 26853991 TI - Migration of intracranial hemostatic clip into the spinal canal: A case report and literature review. AB - Spontaneous migration of intracranial hemostatic clip into the spinal canal is uncommon. We report a case of spontaneous migration of intracranial hemostatic clip into the lumbar spinal canal causing severely painful radiculopathy in a 55 year-old woman. PMID- 26853995 TI - Inertial focusing in non-rectangular cross-section microchannels and manipulation of accessible focusing positions. AB - Inertial focusing in microfluidic channels has been extensively studied experimentally and theoretically, which has led to various applications including microfluidic separation and enrichment of cells. Inertial lift forces are strongly dependent on the flow velocity profile and the channel cross-sectional shape. However, the channel cross-sections studied have been limited to circles and rectangles. We studied inertial focusing in non-rectangular cross-section channels to manipulate the flow profile and thus the inertial focusing of microparticles. The location and number of focusing positions are analyzed with varying cross-sectional shapes and Reynolds number. We found that the broken symmetry of non-equilateral triangular channels leads to the shifting of focusing positions with varying Reynolds number. Non-rectangular channels have unique mapping of the focusing positions and the corresponding basins of attraction. By connecting channels with different cross-sectional shapes, we were able to manipulate the accessible focusing positions and achieve focusing of microparticles to a single stream with ~99% purity. PMID- 26853993 TI - Perceived stress and telomere length: A systematic review, meta-analysis, and methodologic considerations for advancing the field. AB - IMPORTANCE: Psychological stress contributes to numerous diseases and may do so in part through damage to telomeres, protective non-coding segments on the ends of chromosomes. OBJECTIVE: We conducted a systematic review and meta-analysis to determine the association between self-reported, perceived psychological stress (PS) and telomere length (TL). DATA SOURCES: We searched 3 databases (PubMed, PsycInfo, and Scopus), completed manual searches of published and unpublished studies, and contacted all study authors to obtain potentially relevant data. STUDY SELECTION: Two independent reviewers assessed studies for original research measuring (but not necessarily reporting the correlation between) PS and TL in human subjects. 23 studies met inclusion criteria; 22 (totaling 8948 subjects) could be meta-analyzed. DATA EXTRACTION AND SYNTHESIS: We assessed study quality using modified MINORS criteria. Since not all included studies reported PS-TL correlations, we obtained them via direct calculation from author-provided data (7 studies), contact with authors (14 studies), or extraction from the published article (1 study). MAIN OUTCOMES AND MEASURES: We conducted random-effects meta analysis on our primary outcome, the age-adjusted PS-TL correlation. We investigated potential confounders and moderators (sex, life stress exposure, and PS measure validation) via post hoc subset analyses and meta-regression. RESULTS: Increased PS was associated with a very small decrease in TL (n=8724 total; r= 0.06; 95% CI: -0.10, -0.008; p=0.01; alpha=0.025), adjusting for age. This relationship was similar between sexes and within studies using validated measures of PS, and marginally (nonsignificantly) stronger among samples recruited for stress exposure (r=-0.13; vs. general samples: b=-0.11; 95% CI: 0.27, 0.01; p=0.05; alpha=0.013). Publication bias may exist; correcting for its effects attenuated the relationship. CONCLUSIONS AND RELEVANCE: Our analysis finds a very small, statistically significant relationship between increased PS (as measured over the past month) and decreased TL that may reflect publication bias, although fully parsing the effects of publication bias from other sample size correlates is challenging, as discussed. The association may be stronger with known major stressors and is similar in magnitude to that noted between obesity and TL. All included studies used single measures of short-term stress; the literature suggests long-term chronic stress may have a larger cumulative effect. Future research should assess for potential confounders and use longitudinal, multidimensional models of stress. PMID- 26853996 TI - Supramolecular gel-assisted synthesis of double shelled Co@CoO@N-C/C nanoparticles with synergistic electrocatalytic activity for the oxygen reduction reaction. AB - Investigating active, stable, and low-cost materials for the oxygen reduction reaction is one of the key challenges in fuel-cell research. In this work, we describe the formation of N-doped carbon shell coated Co@CoO nanoparticles supported on Vulcan XC-72 carbon materials (Co@CoO@N-C/C) based on a simple supramolecular gel-assisted method. The double-shelled Co@CoO@N-C/C core-shell nanoparticles exhibit superior electrocatalytic activities for the oxygen reduction reaction compared to N-doped carbon and cobalt oxides, demonstrating the synergistic effect of the hybrid nanomaterials. Notably, the Co@CoO@N-C/C nanoparticles give rise to a comparable four-electron selectivity, long-term stability, and high methanol tolerance; all show a multi-fold improvement over the commercial Pt/C catalyst. The progress is of great importance in exploring advanced non-precious metal-based electrocatalysts for fuel cell applications. PMID- 26853994 TI - Dietary fat composition influences glomerular and proximal convoluted tubule cell structure and autophagic processes in kidneys from calorie-restricted mice. AB - Calorie restriction (CR) has been repeatedly shown to prevent cancer, diabetes, hypertension, and other age-related diseases in a wide range of animals, including non-human primates and humans. In rodents, CR also increases lifespan and is a powerful tool for studying the aging process. Recently, it has been reported in mice that dietary fat plays an important role in determining lifespan extension with 40% CR. In these conditions, animals fed lard as dietary fat showed an increased longevity compared with mice fed soybean or fish oils. In this paper, we study the effect of these dietary fats on structural and physiological parameters of kidney from mice maintained on 40% CR for 6 and 18 months. Analyses were performed using quantitative electron microcopy techniques and protein expression in Western blots. CR mitigated most of the analyzed age related parameters in kidney, such as glomerular basement membrane thickness, mitochondrial mass in convoluted proximal tubules and autophagic markers in renal homogenates. The lard group showed improved preservation of several renal structures with aging when compared to the other CR diet groups. These results indicate that dietary fat modulates renal structure and function in CR mice and plays an essential role in the determination of health span in rodents. PMID- 26853997 TI - Visible-light-induced water oxidation by a hybrid photocatalyst consisting of bismuth vanadate and copper(II) meso-tetra(4-carboxyphenyl)porphyrin. AB - Copper(II) meso-tetra(4-carboxyphenyl)porphyrin surface-modified monoclinic scheelite bismuth vanadate (CuTCPP/BiVO4) has been synthesized via a two-step route involving chemisorption of TCPP on BiVO4 and successive Cu(II) ion incorporation into the TCPP, and the surface modification drastically enhances the water oxidation to oxygen (O2) under visible-light irradiation (lambda > 430 nm). PMID- 26853998 TI - Essential oil composition and antibacterial activity of Lindera nacusua (D. Don) Merr. AB - This study represents the first report on the chemical composition and biological activity of the essential oils from the leaves of Lindera nacusua (D. Don) Merr. Twenty-two compounds were identified and quantified, and the major components of the oil were Caryophyllene oxide (8.79%), Hexahydrofarnesyl acetone (6.83%), beta Selinene (5.02%), Neophytadiene (4.53%), Palmitic acid (4.42%), Phytol (4.36%), alpha-Copaene (3.89%), 4a,5,8,8a-beta-Tetrahydro-2,4,5-trimethyl-1,4 naphthalindione (3.83%), alpha-Cadinol (3.17%), Bulnesol (2.65%) and 1,4-Dimethyl 7-(1-methylethyl) azulene (2.38%). The in vitro antibacterial activities of the essential oils were evaluated by the disc diffusion method. The inhibition zones against Staphylococcus aureus and Candida albicans were 23.7 and 23 mm. So the essential oil of L. nacusua showed potent antibacterial activity and potential high selectivity against S. aureus and C. albicans. PMID- 26853999 TI - Various patterns of disrupted daily rest-activity rhythmicity associated with diabetes. AB - Disruptions to sleep and circadian rhythms have now been recognized as common comorbidities in patients with medical illnesses. We aimed to determine if the diurnal rhythms for rest and activity were disrupted in parallel with the development of diabetic complications. Ninety outpatients in our diabetes clinic who had a body mass index <25 kg m(2) wore an actigraph for 7 consecutive days (42 men; mean age 68.7 +/- 8.2 years). Patients with neuropsychiatric diseases, liver cirrhosis, renal failure, chronic obstructive pulmonary disease or blindness, or those who performed shiftwork were excluded. We grouped the actigraph recordings into 1-h periods and counted the number of minutes that showed activity. Stepwise regression analysis showed an association between a diabetic clinical background and measurements of circadian rhythms such as daytime activity, night-time activity, phase, interdaily stability, intradaily variability and relative amplitude. Higher age, body mass index, total cholesterol levels and insulin usage were associated with lower daytime activity and higher intradaily variability, whereas higher haemoglobin A1c levels and the presence of neuropathy were associated with greater daytime activity. The presence of proliferative retinopathy and increased levels of microalbuminuria were associated with higher intradaily variability and lower interdaily stability and amplitude. The presence of cardiovascular disease was associated with advanced phase, whereas painful neuropathy was associated with delayed phase. Our study demonstrated that different diabetic complications were associated independently with a variety of alterations in the circadian rest and activity rhythms. Our findings have provided novel insights that may be helpful in developing interventions for sleep-wake disorders associated with diabetes. PMID- 26854000 TI - Jurassic PARK2: You eat your mitochondria, and you are what your mitochondria eat. AB - Park2/Parkin is a central mediator of selective mitochondrial autophagy for mitochondrial quality control. We showed in mouse hearts that PINK1/Mfn2/Park2 mediated generalized mitophagy is essential to the normal perinatal transition from fetal mitochondria that prefer carbohydrates as metabolic substrates to adult fatty-acid metabolizing mitochondria. Our findings demonstrate how functional interactions between mitophagic mitochondrial removal and biogenic mitochondrial replacement facilitate metabolic maturation of the heart. PMID- 26854001 TI - Tuning of molecular qubits: very long coherence and spin-lattice relaxation times. AB - We report a pulsed EPR study on different transition metal phthalocyanines, elucidating the dependence of spin relaxation on solvent, ligand and metal ion. Coherence times of >40 us and spin-lattice relaxation times of up to 2 s were found. Minimization of SOMO-environment overlap leads to increased coherence times. PMID- 26854002 TI - Efficient kinetic resolution of (RS)-1-phenylethanol by a mycelium-bound lipase from a wild-type Aspergillus oryzae strain. AB - A mycelium-bound lipase from Aspergillus oryzae (AOL) exhibited excellent enantioselectivity for kinetic resolution of (RS)-1-phenylethanol ((RS)-1-PE) in organic solvent. The various reaction parameters affecting the conversion and enantioselectivity were studied, including type of acyl donor, solvent, molar ratio, temperature, enzyme amount, and substrate concentration. The optimum reaction conditions were found to be transesterification with vinyl acetate at 30 degrees C in methyl tert-butyl ether with a vinyl acetate: (RS)-1-PE molar ratio of 1:1 and an enzyme concentration of 60 g/L. At the optimum reaction conditions, the conversion could reach above 46% with >99% enantiomeric excess of the product, (R)-1-phenylethyl acetate, when the substrate concentration was below 1.4 M. The enzyme displayed an excellent enantioselectivity with an E-value of >200 and a strong tolerance for high substrate concentration of up to 1.8 M. Those results indicated that AOL was a promising biocatalyst in the kinetic resolution of (RS)-1-PE. PMID- 26854003 TI - The rise of technology in diabetes care. Not all that is new is necessarily better. AB - Health-care technologies have brought many benefits to the medical profession and to patients. The introduction of the continuous subcutaneous insulin infusion (CSII) pump and continuous glucose monitoring (CGM) devices offers patients with type 1 diabetes (T1D) the opportunity to optimize their blood glucose control and are increasingly being championed as a routine treatment approach for young people. However, the current evidence base does not convincingly support arguments for the generalized application of CSII and CGM into routine clinical practice. The 'patient-medical device interface' is clearly a complex paradigm, and central to its success is the degree of adherence, understanding, and engagement demonstrated by the patient with the technology. The introduction CSII/CGM technologies into the daily routine care of the patient imposes both psychological and 'time-effort' burdens that many patients and families with T1D will find demanding. The current application of these devices cannot therefore be considered a panacea for the self-management of T1D, and raises a number of challenging problems, including those of a practical, health-economic, and ethical nature that need to be fully resolved before it and other emerging technologies can be considered to have achieved this status. PMID- 26854004 TI - Targeted vessel reconstruction in non-contrast-enhanced steady-state free precession angiography. AB - Image quality in non-contrast-enhanced (NCE) angiograms is often limited by scan time constraints. An effective solution is to undersample angiographic acquisitions and to recover vessel images with penalized reconstructions. However, conventional methods leverage penalty terms with uniform spatial weighting, which typically yield insufficient suppression of aliasing interference and suboptimal blood/background contrast. Here we propose a two stage strategy where a tractographic segmentation is employed to auto-extract vasculature maps from undersampled data. These maps are then used to incur spatially adaptive sparsity penalties on vascular and background regions. In vivo steady-state free precession angiograms were acquired in the hand, lower leg and foot. Compared with regular non-adaptive compressed sensing (CS) reconstructions (CSlow ), the proposed strategy improves blood/background contrast by 71.3 +/- 28.9% in the hand (mean +/- s.d. across acceleration factors 1-8), 30.6 +/- 11.3% in the lower leg and 28.1 +/- 7.0% in the foot (signed-rank test, P < 0.05 at each acceleration). The proposed targeted reconstruction can relax trade-offs between image contrast, resolution and scan efficiency without compromising vessel depiction. PMID- 26854005 TI - A novel combination of drug therapy to protect residual hearing post cochlear implant surgery. AB - Conclusions A cocktail combining NAC, Mannitol, and Dexamethasone may be used to prevent loss of residual hearing post-implantation. There is a window of opportunity to treat the cochlea before the onset of cell death in HCs. Objective Inner ear trauma caused by cochlear implant electrode insertion trauma (EIT) initiates multiple molecular mechanisms in hair cells (HCs) or support cells (SCs), resulting in initiation of programmed cell death within the damaged tissues of the cochlea, which leads to loss of residual hearing. In earlier studies L-N-acetylcysteine (L-NAC), Mannitol, and dexamethasone have been shown independently to protect the HCs loss against different types of inner ear trauma. These three molecules have different otoprotective effects. The goal of this preliminary study is to test the efficacy of a combination of these molecules to enhance the otoprotection of HCs against EIT. Methods OC explants were dissected from P-3 rats and placed in serum-free media. Explants were divided into control and experimental groups. CONTROL GROUP: (1) untreated controls; (2) EIT. Experimental group: (1) EIT + L-NAC (5, 2, or 1 mM); (2) EIT + Mannitol (100, 50, or 10 mM); (3) EIT + Dex (20, 10, or 5 MUg/mL); (4) EIT + L NAC + Mannitol + Dex. After EIT was caused in an in-vitro model of CI, explants were cultured in media containing L-NAC alone, Mannitol alone, or Dex alone at decreasing concentrations. Concentrations of L-NAC, Mannitol, and Dex that showed 50% protection of hair cell loss individually were used as a combination in experimental group 4. Results There was an increase of total hair cell (THC) loss in the EIT OC explants when compared with control group HC counts or the tri therapy cochlea. This study defined the dosage of L-NAC, Mannitol, and Dex for the survival of 50% protection of hair cells in vitro. Their combination provided close to 96% protection, demonstrating an additive effect. PMID- 26854007 TI - Availability and toxicity of cadmium to forage grasses grown in contaminated soil. AB - It is important to know the mechanisms for forage development, especially those related to the tolerance of potentially toxic elements, when considering their use in phytoremediation in heavy metal contaminated areas. In this study, we evaluated plant growth, concentration, and the availability of cadmium (Cd) for forage grasses (Panicum maximum Jacq. cv. Aruana and cv. Tanzania; Brachiaria decumbens cv. Basilisk; Brachiaria brizantha cv. Xaraes and cv. Marandu) cultivated in Cd contaminated soils. The experiments were performed under greenhouse conditions over a 90-day evaluation period, and the Cd rates were 2, 4, and 12 mg/kg of soil. The relative growth rate of the forage grasses decreased as Cd rates increased, and the following descending order of susceptibility was observed: Marandu > Xaraes > Aruana > Tanzania > Basilisk, with regard to phytotoxicity in these plants. The forage Cd concentration increased in line with increases in the Cd rates. Cd contents extracted by Mehlich-1 and by diethylenetriaminepentaacetic acid presented high positive correlation with forage relative growth. The forage plants did not block Cd entry into the food chain because they were not capable of limiting Cd absorption. PMID- 26854008 TI - Development and evaluation of real-time PCR assays for bloodmeal identification in Culicoides midges. AB - Culicoides (Diptera: Ceratopogonidae) midges are the biological vectors of a number of arboviruses of veterinary importance. However, knowledge relating to the basic biology of some species, including their host-feeding preferences, is limited. Identification of host-feeding preferences in haematophagous insects can help to elucidate the transmission dynamics of the arboviruses they may transmit. In this study, a series of semi-quantitative real-time polymerase chain reaction (qPCR) assays to identify the vertebrate host sources of bloodmeals of Culicoides midges was developed. Two pan-reactive species group and seven species-specific qPCR assays were developed and evaluated. The assays are quick to perform and less expensive than nucleic acid sequencing of bloodmeals. Using these assays, it was possible to rapidly test nearly 700 blood-fed midges of various species from several geographic locations in Australia. PMID- 26854009 TI - Novel Percutaneous Epicardial Autonomic Modulation in the Canine for Atrial Fibrillation: Results of an Efficacy and Safety Study. AB - BACKGROUND: Endocardial ablation of atrial ganglionated plexi (GP) has been described for treatment of atrial fibrillation (AF). Our objective in this study was to develop percutaneous epicardial GP ablation in a canine model using novel energy sources and catheters. METHODS: Phase 1: The efficacy of several modalities to ablate the GP was tested in an open chest canine model (n = 10). Phase 2: Percutaneous epicardial ablation of GP was done in six dogs using the most efficacious modality identified in phase 1 using two novel catheters. RESULTS: Phase 1: Direct current (DC) in varying doses (blocking [7-12 MUA], electroporation [300-500 MUA], ablation [3,000-7,500 MUA]), radiofrequency ablation (25-50 W), ultrasound (1.5 MHz), and alcohol (2-5 mL) injection were successful at 0/8, 4/12, 5/7, 3/8, 1/5, and 5/7 GP sites. DC (500-5,000 MUA) along with alcohol irrigation was tested in phase 2. Phase 2: Percutaneous epicardial ablation of the right atrium, oblique sinus, vein of Marshall, and transverse sinus GP was successful in 5/6 dogs. One dog died of ventricular fibrillation during DC ablation at 5,000 MUA. Programmed stimulation induced AF in six dogs, preablation and no atrial arrhythmia in three, flutter in one, and AF in one postablation. Heart rate, blood pressure, effective atrial refractory period, and local atrial electrogram amplitude did not change significantly postablation. Microscopic examination showed elimination of GP, and minimal injury to atrial myocardium. CONCLUSION: Percutaneous epicardial ablation of GP using DC and novel catheters is safe and feasible and may be used as an adjunct to pulmonary vein isolation in the treatment of AF in order to minimize additional atrial myocardial ablation. PMID- 26854013 TI - Treatment: Concepts and new developments. PMID- 26854010 TI - Molecular characterization of HCV in a Swedish county over 8 years (2002-2009) reveals distinct transmission patterns. AB - BACKGROUND: Hepatitis C virus (HCV) is a major public health concern and data on its molecular epidemiology in Sweden is scarce. We carried out an 8-year population-based study of newly diagnosed HCV cases in one of Sweden's centrally situated counties, Sodermanland (D-county). The aim was to characterize the HCV strains circulating, analyze their genetic relatedness to detect networks, and in combination with demographic data learn more about transmission. METHODS: Molecular analyses of serum samples from 91% (N=557) of all newly notified cases in D-county, 2002-2009, were performed. Phylogenetic analysis (NS5B gene, 300 bp) was linked to demographic data from the national surveillance database, SmiNet, to characterize D-county transmission clusters. The linear-by-linear association test (LBL) was used to analyze trends over time. RESULTS: The most prevalent subtypes were 1a (38%) and 3a (34%). Subtype 1a was most prevalent among cases transmitted via sexual contact, via contaminated blood, or blood products, while subtype 3a was most prevalent among people who inject drugs (PWIDs). Phylogenetic analysis revealed that the subtype 3a sequences formed more and larger transmission clusters (50% of the sequences clustered), while the 1a sequences formed smaller clusters (19% of the sequences clustered), possibly suggesting different epidemics. CONCLUSION: We found different transmission patterns in D county which may, from a public health perspective, have implications for how to control virus infections by targeted interventions. PMID- 26854014 TI - Short-contact, low-dose methyl aminolaevulinate photodynamic therapy for acne vulgaris. PMID- 26854016 TI - Response to "Perivascular adipose tissue and inflammation. PMID- 26854015 TI - Computational meta-analysis of statistical parametric maps in major depression. AB - OBJECTIVE: Several neuroimaging meta-analyses have summarized structural brain changes in major depression using coordinate-based methods. These methods might be biased toward brain regions where significant differences were found in the original studies. In this study, a novel voxel-based technique is implemented that estimates and meta-analyses between-group differences in grey matter from individual MRI studies, which are then applied to the study of major depression. METHODS: A systematic review and meta-analysis of voxel-based morphometry studies were conducted comparing participants with major depression and healthy controls by using statistical parametric maps. Summary effect sizes were computed correcting for multiple comparisons at the voxel level. Publication bias and heterogeneity were also estimated and the excess of heterogeneity was investigated with metaregression analyses. RESULTS: Patients with major depression were characterized by diffuse bilateral grey matter loss in ventrolateral and ventromedial frontal systems extending into temporal gyri compared to healthy controls. Grey matter reduction was also detected in the right parahippocampal and fusiform gyri, hippocampus, and bilateral thalamus. Other areas included parietal lobes and cerebellum. There was no evidence of statistically significant publication bias or heterogeneity. CONCLUSIONS: The novel computational meta-analytic approach used in this study identified extensive grey matter loss in key brain regions implicated in emotion generation and regulation. Results are not biased toward the findings of the original studies because they include all available imaging data, irrespective of statistically significant regions, resulting in enhanced detection of additional areas of grey matter loss. PMID- 26854017 TI - A physical mechanism of cancer heterogeneity. AB - We studied a core cancer gene regulatory network motif to uncover possible source of cancer heterogeneity from epigenetic sources. When the time scale of the protein regulation to the gene is faster compared to the protein synthesis and degradation (adiabatic regime), normal state, cancer state and an intermediate premalignant state emerge. Due to the epigenetics such as DNA methylation and histone remodification, the time scale of the protein regulation to the gene can be slower or comparable to the protein synthesis and degradation (non-adiabatic regime). In this case, many more states emerge as possible phenotype alternations. This gives the origin of the heterogeneity. The cancer heterogeneity is reflected from the emergence of more phenotypic states, larger protein concentration fluctuations, wider kinetic distributions and multiplicity of kinetic paths from normal to cancer state, higher energy cost per gene switching, and weaker stability. PMID- 26854018 TI - Characteristics of Antioxidant Systems of Yellow Fraction of Red Deer's (Cervus elaphus L.) Semen During the Rutting Period. AB - The objective of this study was to make the preliminary characterization of the antioxidant defence systems of the yellow fraction (YF) of red deer's (Cervus elaphus L.) semen during the rutting period. The semen was collected using artificial vagina (AV). The studies included spectrophotometric determination of antioxidant enzymes activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). We also analysed the contents of low-molecular antioxidants such as L-glutathione (GSH + GSSG), L-ascorbate (ASC) and total antioxidant status (TAS). Additionally, the samples were subjected to PAGE and stained for SOD and GPx activities. It was demonstrated that the yellow fraction exhibited activities of SOD and GPx, with the highest activities in September and October. CAT activity was not detected. Staining for the SOD and GPx activities confirmed three protein bands with SOD activity and one protein band with GPx activity. The content of GSH + GSSG was similar in trials dating from October to December contrary to the content of ASC which was high in samples from September and October. The stable rate of TAS was observed during the whole rutting period. The results of this study showed that the YF of red deer semen is equipped with basic battery of antioxidant enzymes comprising SOD and GPx, with the supporting role of GSH + GSSG and ASC. Moreover, the samples obtained at the peak of the rutting period occurring from September to October had the highest enzymatic activity in comparison with remaining months of the rutting period, which contributed to the high quality of the semen by preventing it from the formation of oxidative stress during the short period of intense sexual activity of male red deer. The better understanding of the mechanisms of antioxidant defence systems in the YF of deer's semen may contribute to the potential use of this fraction in technology of wild ruminant semen preservation. PMID- 26854019 TI - Convergent production and tolerance among 107 woody species and divergent production between shrubs and trees. AB - Green leaves face two fundamental challenges (i.e., carbon fixation and stress tolerance) during their lifespan. However, the relationships between leaf production potential and leaf tolerance potential have not been explicitly tested with a broad range of plant species in the same environment. To do so, we conducted a field investigation based on 107 woody plants grown in a common garden and complementary laboratory measurements. The values, as measured by a chlorophyll meter, were significantly related to the direct measurements of chlorophyll content on a leaf area basis. Area-based chlorophyll content was positively correlated with root surface area, whole-plant biomass, leaf mass per area (LMA), and force to punch. Additionally, LMA had a positive correlation with force to punch. Shrubs had a higher leaf chlorophyll content than trees; however, shrubs and trees exhibited a similar leaf lifespan, force to punch, and LMA. These findings suggest that the production potential of leaves and their tolerance to stresses may be convergent in woody species and that the leaf production potential may differ between shrubs and trees. This study highlights the possibility that functional convergence and divergence might be linked to long-term selection pressures and genetic constraints. PMID- 26854020 TI - Low-Income Immigrant Hispanic Mothers' Concerns and Perceptions of Their Young Child's Weight. AB - OBJECTIVES: To describe how low-income Hispanic immigrant mothers' concerns and perceptions of her child's health, along with her concerns for herself becoming overweight, relate to her (a) concerns that her child will become overweight and (b) underestimation of her child's weight status. DESIGN AND SAMPLE: Cross sectional survey and direct body composition assessments were collected among 96 low-income Hispanic mothers and their young children from Houston-area community centers. MEASURES: Data were collected on maternal concerns and perceptions of child's weight and health, concerns about her own weight, demographic characteristics, and measured child's height and weight. RESULTS: Fifty-four percent of mothers with an overweight/obese child perceived their child was "about the right weight." Mothers concerned with becoming overweight themselves had 3 times higher odds of being concerned that her child would become overweight (OR = 3.01, p < .01). Mothers who perceived their child as less healthy had approximately 2 times higher odds of underestimating their child's weight (OR = 1.86, p < .01). CONCLUSIONS: Short screeners that focus on maternal concerns about herself and her child becoming overweight, along with perceptions of her child's health and weight status, may assist nurses in effectively tailoring their health message at point of care. PMID- 26854021 TI - Preferential location of idiopathic peptic ulcers. AB - OBJECTIVE: Helicobacter pylori infection-negative, nonsteroidal antiinflammatory drugs (NSAIDs)-negative peptic ulcers, which are termed idiopathic peptic ulcers (IPUs), have been increasing worldwide. In this study, we investigated the preferential locations of gastric ulcers according to their cause (e.g., H. pylori and NSAIDs), with special attention to IPUs. MATERIAL AND METHODS: A total of 361 patients consecutively diagnosed with a peptic ulcer over a period of one year were classified into four groups according to H. pylori-infection status and NSAIDs usage. The ulcer location was divided into the antrum, angularis, and body, and was compared among the four ulcer groups. RESULTS: The ulcers of 43 patients were classified as IPUs. Compared with simple H. pylori ulcers, IPUs more preferentially located in the antrum (14% vs. 52%, p < 0.01). The difference was more pronounced in the analysis of IPUs in which patients with a history of H. pylori eradication or those with severe atrophic gastritis were excluded, and 79% of these IPUs were located in the antrum. With duodenal ulcers taken together, the vast majority of (86%) these IPUs occurred in the duodenal bulb or the antrum. The proportion of antral ulcers in NSAISs users also differed depending on the presence of concomitant H. pylori infection (positive: 22% vs. negative: 62%, p < 0.01). CONCLUSION: There was a striking difference in the ulcer location within the stomach depending on the cause of the ulcer, and IPUs predominantly occurred in the antrum. This information on the preferential locations of ulceration should provide endoscopists with some hints concerning the etiology of ulcers. PMID- 26854022 TI - Nonparametric survival analysis using Bayesian Additive Regression Trees (BART). AB - Bayesian additive regression trees (BART) provide a framework for flexible nonparametric modeling of relationships of covariates to outcomes. Recently, BART models have been shown to provide excellent predictive performance, for both continuous and binary outcomes, and exceeding that of its competitors. Software is also readily available for such outcomes. In this article, we introduce modeling that extends the usefulness of BART in medical applications by addressing needs arising in survival analysis. Simulation studies of one-sample and two-sample scenarios, in comparison with long-standing traditional methods, establish face validity of the new approach. We then demonstrate the model's ability to accommodate data from complex regression models with a simulation study of a nonproportional hazards scenario with crossing survival functions and survival function estimation in a scenario where hazards are multiplicatively modified by a highly nonlinear function of the covariates. Using data from a recently published study of patients undergoing hematopoietic stem cell transplantation, we illustrate the use and some advantages of the proposed method in medical investigations. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26854023 TI - A Binding Site on IL-17A for Inhibitory Macrocycles Revealed by Hydrogen/Deuterium Exchange Mass Spectrometry. AB - Computational assessment of the IL-17A structure identified two distinct binding pockets, the beta-hairpin pocket and the alpha-helix pocket. The beta-hairpin pocket was hypothesized to be the site of binding for peptide macrocycles. Support for this hypothesis was obtained using HDX-MS which revealed protection to exchange only within the beta-hairpin pocket. This data represents the first direct structural evidence of a small molecule binding site on IL-17A that functions to disrupt the interaction with its receptor. PMID- 26854025 TI - Deregulation of HOX genes by DNMT3A and MLL mutations converges on BMI1. PMID- 26854024 TI - JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma. AB - Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available. PMID- 26854027 TI - An isoform-specific C/EBPbeta inhibitor targets acute myeloid leukemia cells. PMID- 26854028 TI - Event-related potential indices of congruency sequence effects without feature integration or contingency learning confounds. AB - The congruency effect in Stroop-like tasks (i.e., increased response time and reduced accuracy in incongruent relative to congruent trials) is often smaller when the previous trial was incongruent as compared to congruent. This congruency sequence effect (CSE) is thought to reflect cognitive control processes that shift attention to the target and/or modulate the response engendered by the distracter differently after incongruent relative to congruent trials. The neural signatures of CSEs are therefore usually attributed to cognitive control processes that minimize distraction from irrelevant stimuli. However, CSEs in previous functional neuroimaging studies were ubiquitously confounded with feature integration and/or contingency learning processes. We therefore investigated whether a neural CSE can be observed without such confounds in a group of healthy young adults (n = 56). To this end, we combined a prime-probe task that lacks such confounds with high-density ERPs to identify, for the first time, the neural time course of confound-minimized CSEs. Replicating recent behavioral findings, we observed strong CSEs in this task for mean response time and mean accuracy. Critically, conceptually replicating prior ERP results from confounded tasks, we also observed a CSE in both the parietal conflict slow potential (conflict SP) and the frontomedial N450. These findings indicate for the first time that neural CSEs as indexed by ERPs can be observed without the typical confounds. More broadly, the present study provides a confound-minimized protocol that will help future researchers to better isolate the neural bases of control processes that minimize distraction from irrelevant stimuli. PMID- 26854026 TI - Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both. AB - The Philadelphia-negative myeloproliferative neoplasms (MPNs) are clonal disorders involving hematopoietic stem and progenitor cells and are associated with myeloproliferation, splenomegaly and constitutional symptoms. Similar signs and symptoms can also be found in patients with chronic inflammatory diseases, and inflammatory processes have been found to play an important role in the pathogenesis and progression of MPNs. Signal transduction pathways involving JAK1, JAK2, STAT3 and STAT5 are causally involved in driving both the malignant cells and the inflammatory process. Moreover, anti-inflammatory and immune modulating drugs have been used successfully in the treatment of MPNs. However, to date, many unresoved issues remain. These include the role of somatic mutations that are present in addition to JAK2V617F, CALR and MPL W515 mutations, the interdependency of malignant and nonmalignant cells and the means to eradicate MPN-initiating and -maintaining cells. It is imperative for successful therapeutic approaches to define whether the malignant clone or the inflammatory cells or both should be targeted. The present review will cover three aspects of the role of inflammation in MPNs: inflammatory states as important differential diagnoses in cases of suspected MPN (that is, in the absence of a clonal marker), the role of inflammation in MPN pathogenesis and progression and the use of anti inflammatory drugs for MPNs. The findings emphasize the need to separate the inflammatory processes from the malignancy in order to improve our understanding of the pathogenesis, diagnosis and treatment of patients with Philadelphia negative MPNs. PMID- 26854030 TI - Graphene as Transparent Electrodes: Fabrication and New Emerging Applications. AB - Graphene has been regarded as a promising candidate for a new generation of transparent electrodes (TEs) due to its prominent characteristics including high optical transmittance, exceptional electronic transport, outstanding mechanical strength, and environmental stability. Comprehensive and critical insights into the latest advances in graphene-based TEs (GTEs) since, but not limited to 2013, are provided, with an emphasis on fabrication, modification, and versatile applications. Several emerging application areas not previously summarized, including electrochromic devices, supercapacitors, electrochemical and electrochemiluminescent sensors, are discussed in detail. The challenges and prospects in these fields are also addressed. PMID- 26854029 TI - KRAS insertion mutations are oncogenic and exhibit distinct functional properties. AB - Oncogenic KRAS mutations introduce discrete amino acid substitutions that reduce intrinsic Ras GTPase activity and confer resistance to GTPase-activating proteins (GAPs). Here we discover a partial duplication of the switch 2 domain of K-Ras encoding a tandem repeat of amino acids G60_A66dup in a child with an atypical myeloproliferative neoplasm. K-Ras proteins containing this tandem duplication or a similar five amino acid E62_A66dup mutation identified in lung and colon cancers transform the growth of primary myeloid progenitors and of Ba/F3 cells. Recombinant K-Ras(G60_A66dup) and K-Ras(E62_A66dup) proteins display reduced intrinsic GTP hydrolysis rates, accumulate in the GTP-bound conformation and are resistant to GAP-mediated GTP hydrolysis. Remarkably, K-Ras proteins with switch 2 insertions are impaired for PI3 kinase binding and Akt activation, and are hypersensitive to MEK inhibition. These studies illuminate a new class of oncogenic KRAS mutations and reveal unexpected plasticity in oncogenic Ras proteins that has diagnostic and therapeutic implications. PMID- 26854031 TI - Synergism of perampanel and zonisamide in the rat amygdala kindling model of temporal lobe epilepsy. AB - OBJECTIVE: Anticonvulsive monotherapy fails to be effective in one third of patients with epilepsy resulting in the need for polytherapy regimens. However, with the still limited knowledge, drug choices for polytherapy remain empirical. Here we report experimental data from a chronic epilepsy model for the combination of perampanel and zonisamide, which can render guidance for clinical studies and individual drug choices. METHODS: The anticonvulsant effects of the combination of perampanel and zonisamide were evaluated in a rat amygdala kindling model. Furthermore, the potential for motor impairment was evaluated. The type of interaction was quantitatively assessed based on isobolographic analysis. RESULTS: When administered alone, zonisamide dose-dependently increased the afterdischarge threshold in fully kindled rats. Moreover, data confirmed efficacy of perampanel to inhibit seizure initiation and progression with an impact on propagation of activity from the focus. Pronounced threshold increases were observed following administration of a constant zonisamide dosage combined with different doses of perampanel. Isobolographic analysis of drug responses, which is based on individual drug dose-effect data, revealed a synergistic interaction substantiating the high efficacy of the combination. Furthermore, rotarod data indicated that the combination has a favorable tolerability profile when zonisamide is coadministered with low doses of perampanel. Plasma concentration analysis argued against a pharmacokinetic interaction as a basis for the synergism. SIGNIFICANCE: The findings clearly indicate a pronounced synergistic anticonvulsant effect for the combination of the noncompetitive alpha amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel with zonisamide, which modulates voltage-sensitive sodium channels and T-type calcium currents. Consequently, polytherapy using these two antiepileptic drugs might be efficacious for clinical management of partial-onset seizures. The findings indicate that the impact of dose ratios on tolerability needs be taken into account. With regard to conclusions about the extent of the synergism and its implications further antiepileptic drug combinations need to be evaluated allowing direct comparison. PMID- 26854032 TI - Visual Field Change and 24-Hour IOP-Related Profile with a Contact Lens Sensor in Treated Glaucoma Patients. AB - PURPOSE: To test the hypothesis that a 24-hour recording of intraocular pressure (IOP)-related measurements derived from a contact lens sensor (CLS) correlates to the rate of visual field progression in treated glaucomatous eyes. DESIGN: Prospective, cross-sectional study. PARTICIPANTS: Forty treated glaucomatous patients with 8 or more 24-2 visual field tests. METHODS: Twenty-four-hour recording with a CLS that provides IOP-related measurements. MAIN OUTCOME MEASURES: Rates of visual field mean deviation (MD) change before and at the time of CLS recording and CLS parameters, namely number of large peaks, mean peak ratio, wake-to-sleep slope, amplitude and area under the cosine curve, and variability from the mean. RESULTS: When comparing the rate of MD change before and at the time of CLS recording of all patients, the average slope was -0.05 dB/year faster in the beginning compared with the end (P = 0.087), suggesting a deceleration of progression by the time of CLS recording. The number of long peaks and the mean peak ratio when patients were awake were the best predictors of faster progression. The combination of CLS parameters provided better measures of goodness of fit than Goldmann IOP parameters (mean, peak, and fluctuation) in the same period. CONCLUSIONS: Intraocular pressure-related parameters obtained with 24-hour recording with a CLS were associated with the rate of visual field progression in treated glaucomatous eyes. This technology may be useful in detecting eyes at higher risk of glaucoma progression while receiving treatment. PMID- 26854033 TI - Cataract Surgery and Mortality in the United States Medicare Population. AB - PURPOSE: To determine the association between cataract surgery and all-cause mortality in United States Medicare patients with cataract. DESIGN: Retrospective cohort study. PARTICIPANTS: A 5% random sample of United States Medicare beneficiaries with a diagnosis of cataract from the 2002 through 2012 Denominator and Physician/Supplier Part B files. METHODS: The exposure of interest was cataract surgery and the outcome of interest was all-cause mortality. Baseline characteristics that were examined included demographics, systemic comorbidities, and ocular comorbidities. Cox proportional hazards regression modeling was used to assess the association between cataract surgery and mortality. Additional subgroup analyses were performed in propensity score deciles and within strata of age, gender, region, systemic disease burden, and in patients with versus without severe cataract subtypes. MAIN OUTCOME MEASURES: All-cause mortality. RESULTS: The 5% Medicare sample included 1 501 420 patients with cataract, of whom 544 984 (36.3%) underwent cataract surgery. Patients with cataract surgery were followed up for a mean of 11.4 quarters (standard deviation [SD], 10.8 quarters; range, 0.0-44.0 quarters), whereas patients without cataract surgery were followed up for a mean of 12.9 quarters (SD, 12.2 quarters; range, 0.0-44.0 quarters). Mortality incidence was 2.78 deaths per 100 person-years in patients with cataract surgery and 2.98 deaths per 100 person-years in patients without surgery (P < 0.0001). Overall, patients with cataract surgery had a lower adjusted hazard of mortality compared with patients without surgery (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.72-0.74). The strongest associations were observed in patients with a high propensity score decile (HR, 0.52; 95% CI, 0.50-0.54), patients 80 to 84 years of age (HR, 0.63; 95% CI, 0.62-0.65), women (HR, 0.69; 95% CI, 0.68-0.70), patients in the western United States (HR, 0.52; 95% CI, 0.32 0.86), patients with a moderate systemic disease burden (HR, 0.71; 95% CI, 0.69 0.72), and patients with severe cataract (HR, 0.68; 95% CI, 0.66-0.70). CONCLUSIONS: In a national cohort of United States Medicare beneficiaries with cataract, cataract surgery was associated with decreased all-cause mortality. Further studies are needed to examine mechanisms surrounding the association between cataract surgery and mortality. PMID- 26854034 TI - Bifocals Fail to Improve Stereopsis Outcomes in High AC/A Accommodative Esotropia. AB - PURPOSE: To assess whether stereopsis outcomes of patients with accommodative esotropia with high accommodative convergence/accommodation relationship (AC/A) were improved after treatment with bifocal glasses compared with single-vision lenses. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients with high AC/A accommodative esotropia; evidence of stereopsis, binocularity (on Worth 4-dot testing), or improvement in near angle with +3.00 D lenses; and at least 4 years of records available for review, who were seen in the Department of Ophthalmology at Boston Children's Hospital between 2006 and 2014. METHODS: Use of bifocal or single-vision glasses. Charts were reviewed retrospectively. Stereopsis was log transformed for statistical analysis. Linear (for stereopsis) or logistic (for surgery) regression was used to control for confounders. MAIN OUTCOME MEASURES: Stereopsis at final follow-up, difference in stereopsis between final and initial visits, and progression to strabismus surgery. Secondary outcomes included final near and distance deviations. RESULTS: Of the 180 patients who met inclusion criteria, 77 used bifocals and 103 used single-vision lenses. Bifocals did not improve stereopsis outcomes compared with single-vision lenses. In both groups, stereopsis was similar at the initial and final visits, with similar improvement in both groups. Children in the bifocal group had a 3.6-fold higher rate of strabismus surgery than children in the single-lens group (P = 0.04.) Additionally, children in the bifocal group had near deviations 4 PD larger than those with single lenses at final follow-up, even after controlling for age and initial deviation (P = 0.02). These results did not change if surgical patients were eliminated or in the subgroup with initial distance deviation of 0 PD in full hyperopic correction. CONCLUSIONS: Despite their widespread use, there is no evidence that bifocals improve outcomes in children with accommodative esotropia with high AC/A. In our retrospective review, children with bifocals had higher surgical rates and a smaller improvement in near deviation over time. Although our results suggest that eliminating bifocals could reduce the cost and complexity of care while potentially improving quality, prospective, randomized controlled trials are needed to determine whether a change in practice is warranted. PMID- 26854036 TI - Genetic Associations of Primary Angle-Closure Disease: A Systematic Review and Meta-analysis. AB - TOPIC: Systematic review and meta-analysis of the genetic associations of primary angle-closure disease (PACD). CLINICAL RELEVANCE: To confirm the genetic biomarkers for PACD, including primary angle-closure glaucoma (PACG) and related phenotypes. METHODS: We searched in the MEDLINE and EMBASE databases for genetic studies of PACG or other PACD published from the start dates of the databases to May 11, 2015. We estimated the summary odds ratios (ORs) and 95% confidence intervals (CIs) for each polymorphism in PACG, primary angle-closure suspect (PACS), and primary angle-closure (PAC) using fixed- or random-effect models. We also performed sensitivity analysis to test the robustness of the results. RESULTS: Our literature search yielded 6463 reports. Among them, we identified 24 studies that fulfilled the eligibility criteria for meta-analysis, involving 28 polymorphisms in 11 genes/loci. We affirmed the association of PACG and combined PACS/PAC/PACG with 10 polymorphisms in 8 genes/loci, including COL11A1 (rs3753841 G, OR, 1.22; P = 0.00046), HGF (rs17427817-C, OR, 2.02; P = 6.9E-07; rs5745718-A, OR, 2.11; P = 9.9E-07), HSP70 (rs1043618, GG+GC, OR, 0.52; P = 0.0010), MFRP (rs2510143-C, OR, 0.66; P = 0.012; rs3814762-G, OR, 1.40; P = 0.0090), MMP9 (rs3918249-C, OR, 1.35; P = 0.034), NOS3 (rs7830-A, OR, 0.80; P = 0.036), PLEKHA7 (rs11024102-G, OR, 1.24; P = 8.3E-05), and PCMTD1-ST18 (rs1015213-A, OR, 1.59; P = 0.00013). Sensitivity analysis indicated that the results were robust. CONCLUSIONS: In this study, we confirmed multiple polymorphisms in 8 genes/loci as genetic biomarkers for PACD, among which 3 were identified in a genome-wide association study (COL11A1, PLEKHA7, and PCMTD1-ST18), and 5 were identified in candidate gene studies (HGF, HSP70, MFRP, MMP9, and NOS3). PMID- 26854035 TI - The Pediatric Choroidal and Ciliary Body Melanoma Study: A Survey by the European Ophthalmic Oncology Group. AB - PURPOSE: To collect comprehensive data on choroidal and ciliary body melanoma (CCBM) in children and to validate hypotheses regarding pediatric CCBM: children younger than 18 years, males, and those without ciliary body involvement (CBI) have more favorable survival prognosis than young adults 18 to 24 years of age, females, and those with CBI. DESIGN: Retrospective, multicenter observational study. PARTICIPANTS: Two hundred ninety-nine patients from 24 ocular oncology centers, of whom 114 were children (median age, 15.1 years; range, 2.7-17.9 years) and 185 were young adults. METHODS: Data were entered through a secure website and were reviewed centrally. Survival was analyzed using Kaplan-Meier analysis and Cox proportional hazards regression. MAIN OUTCOME MEASURES: Proportion of females, tumor-node-metastasis (TNM) stage, cell type, and melanoma related mortality. RESULTS: Cumulative frequency of having CCBM diagnosed increased steadily by 0.8% per year of age between 5 and 10 years of age and, after a 6-year transition period, by 8.8% per year from age 17 years onward. Of children and young adults, 57% and 63% were female, respectively, which exceeded the expected 51% among young adults. Cell type, known for 35% of tumors, and TNM stage (I in 22% and 21%, II in 49% and 52%, III in 30% and 28%, respectively) were comparable for children and young adults. Melanoma-related survival was 97% and 90% at 5 years and 92% and 80% at 10 years for children compared with young adults, respectively (P = 0.013). Males tended to have a more favorable survival than females among children (100% vs. 85% at 10 years; P = 0.058). Increasing TNM stage was associated with poorer survival (stages I, II, and III: 100% vs. 86% vs. 76%, respectively; P = 0.0011). By multivariate analysis, being a young adult (adjusted hazard rate [HR], 2.57), a higher TNM stage (HR, 2.88 and 8.38 for stages II and III, respectively), and female gender (HR, 2.38) independently predicted less favorable survival. Ciliary body involvement and cell type were not associated with survival. CONCLUSIONS: This study confirms that children with CCBM have a more favorable survival than young adults 18 to 25 years of age, adjusting for TNM stage and gender. The association between gender and survival varies between age groups. PMID- 26854037 TI - Aryl Hydrocarbon Receptor-Interacting Protein-Like 1 in Cancer-Associated Retinopathy. PMID- 26854038 TI - Neonatal Risk Factors for Treatment-Demanding Retinopathy of Prematurity: A Danish National Study. AB - PURPOSE: One goal of the study was to identify "new" statistically independent risk factors for treatment-demanding retinopathy of prematurity (ROP). Another goal was to evaluate whether any new risk factors could explain the increase in the incidence of treatment-demanding ROP over time in Denmark. DESIGN: A retrospective, register-based cohort study. PARTICIPANTS: The study included premature infants (n = 6490) born in Denmark from 1997 to 2008. METHODS: The study sample and the 31 candidate risk factors were identified in 3 national registers. Data were linked through a unique civil registration number. Each of the 31 candidate risk factors were evaluated in univariate analyses, while adjusted for known risk factors (i.e., gestational age [GA] at delivery, small for gestational age [SGA], multiple births, and male sex). Significant outcomes were analyzed thereafter in a backward selection multiple logistic regression model. MAIN OUTCOME MEASURES: Treatment-demanding ROP and its associations to candidate risk factors. RESULTS: Mechanical ventilation (odds ratio [OR], 2.84; 95% confidence interval [CI], 1.99-4.08; P < 0.01) and blood transfusion (OR, 1.97; 95% CI, 1.20-3.14; P = 0.01) were the only new statistically independent risk factors, in addition to GA at delivery, SGA, multiple births, and male sex. Modification in these prognostic factors for ROP did not cause an increase in treatment-demanding ROP. CONCLUSIONS: In a large study population, blood transfusion and mechanical ventilation were the only new statistically independent risk factors to predict the development of treatment-demanding ROP. Modification in the neonatal treatment with mechanical ventilation or blood transfusion did not cause the observed increase in the incidence of preterm infants with treatment-demanding ROP during a recent birth period (2003-2008). PMID- 26854039 TI - Progressing Scintillating Scotoma Captured on Automated Visual Field Testing. PMID- 26854040 TI - Segmentation Errors in Macular Ganglion Cell Analysis as Determined by Optical Coherence Tomography. AB - PURPOSE: To investigate the prevalence, features, associated factors, and reproducibility of segmentation errors in macular ganglion cell inner plexiform layer (GCIPL) thickness measurement as determined by optical coherence tomography (OCT). DESIGN: Cross-sectional study. PARTICIPANTS: Five hundred thirty-eight glaucomatous and healthy eyes from 290 subjects with OCT-measured macular GCIPL thickness were enrolled. Eyes with macular disorders, including epiretinal membrane, macular degeneration, macular hole, and myopic maculopathy, were excluded. METHODS: By inspecting 128 cross-sectional OCT B-scan images per eye, the presence (yes vs. no), layer (anterior vs. posterior border), location (quadrants), and area (diffuse vs. focal) of macular GCIPL segmentation error were investigated. The effects of age, refractive error, mean deviation of visual field test, circumpapillary retinal nerve fiber layer thickness obtained by OCT, and signal strength of OCT scan on the presence of macular GCIPL segmentation errors were evaluated. In eyes with segmentation errors, repeated OCT examinations were performed to investigate the reproducibility of the segmentation errors. MAIN OUTCOME MEASURES: The prevalence, features, associated factors, and reproducibility of macular GCIPL segmentation errors were assessed. RESULTS: Among the 538 eyes, 52 eyes (9.7%) showed segmentation errors in macular GCIPL thickness measurement. The most common features of segmentation errors were that they affected both the anterior and posterior borders, were located at the nasal quadrant (centered to the fovea), and were diffuse. In univariate analysis, the presence of segmentation error was associated significantly with younger age (P < 0.001), higher degree of myopia (P < 0.001), and lower signal strength of OCT scan (P = 0.038). In multivariate analysis, only higher degree of myopia was associated significantly with the presence of segmentation error (P < 0.001). In repeated examinations, segmentation errors were reproducible in 24 eyes (46.2%). In other cases, the features of segmentation errors changed or disappeared. CONCLUSIONS: Although the OCT segmentation algorithm accurately detected macular GCIPL thickness in most eyes without macular disorders, in some cases, segmentation errors were found, especially in myopic eyes. In repeated examinations, approximately half of the errors were nonreproducible. These findings should be considered when assessing macular GCIPL thickness using OCT. PMID- 26854042 TI - Mobile- versus fixed-bearing total knee arthroplasty: a prospective randomized controlled trial featuring 6-10-year follow-up. AB - OBJECTIVE: The purpose of this study was to compare long-term clinical and radiographic outcomes of mobile- (MB) and fixed-bearing (FB) total knee arthroplasties (TKA). METHODS: A randomized controlled study was conducted to compare the clinical and radiographic outcomes of MB and FB prostheses in 93 consecutive patients who underwent primary TKA for knee osteoarthritis. Mean follow-up of the patients was 100.9 months in the MB group (range: 78-121 months) and 93.7 months (range: 78-120 months) in the FB group. The clinical results were graded according to the Knee Society Knee Score (KSKS) and the Knee Society Functional Score (KSFS). Secondary outcomes included pain, patellofemoral joint function, quality of life (QOL), and radiologic outcomes (Knee Society's roentgenographic evaluation system). RESULTS: Although there was significant improvement in both groups, there were no significant differences between the groups with respect to mean KSFS and radiologic outcomes. However, mean pain score of the MB group was significantly higher than that of the FB group (48.83+/ 0.62 vs 47.39+/-0.86, respectively, p=0.011), and mean KSKS was significantly higher than that of the FB group (93.5+/-6.2 vs 89.7+/-6.9, respectively, p=0.007). CONCLUSION: TKA clinical results were satisfactory in both the MB and FB groups. KSKS and pain scores were significantly better in the MB than in the FB group. However, no differences were found in other assessments. Thus, we conclude that the best design is the one with which the surgeon is most comfortable and most able to implant reproducibly. PMID- 26854041 TI - An integrative approach for analyzing hundreds of neurons in task performing mice using wide-field calcium imaging. AB - Advances in neurotechnology have been integral to the investigation of neural circuit function in systems neuroscience. Recent improvements in high performance fluorescent sensors and scientific CMOS cameras enables optical imaging of neural networks at a much larger scale. While exciting technical advances demonstrate the potential of this technique, further improvement in data acquisition and analysis, especially those that allow effective processing of increasingly larger datasets, would greatly promote the application of optical imaging in systems neuroscience. Here we demonstrate the ability of wide-field imaging to capture the concurrent dynamic activity from hundreds to thousands of neurons over millimeters of brain tissue in behaving mice. This system allows the visualization of morphological details at a higher spatial resolution than has been previously achieved using similar functional imaging modalities. To analyze the expansive data sets, we developed software to facilitate rapid downstream data processing. Using this system, we show that a large fraction of anatomically distinct hippocampal neurons respond to discrete environmental stimuli associated with classical conditioning, and that the observed temporal dynamics of transient calcium signals are sufficient for exploring certain spatiotemporal features of large neural networks. PMID- 26854043 TI - Prevalence and characteristics of noise in a series of 282 ceramic-on-ceramic total hip arthroplasties. AB - OBJECTIVE: The aim of this study was to determine the prevalence of noise with ceramic-on-ceramic (COC) bearings in total hip arthroplasty (THA). We evaluated if patients wished be counseled about this and its potential consequences preoperatively. METHODS: Two hundred eighty-two primary cementless THAs were performed in 260 patients (124 males and 136 females), with a mean age 68.5 years. All patients completed a questionnaire. Minimum follow-up was 3 years. Statistical analysis was used to evaluate if patient variables influenced whether the patient experienced a noisy hip. RESULTS: Thirty-one (11%) of hips had an audible noise; 50% of these were 'squeaks.' The noise was mainly present upon standing up (74%) and walking (45%). None of the patients noted 'noise' on their consent forms. Fifty-five percent of the entire cohort would have preferred to have known about the possibility of a noisy hip before consenting, though no patients would have refused consent had they known about the noise preoperatively. No patients have sought financial compensation to date. There was no significant influence of gender (p=0.92), age (p=0.66), height (p=0.17), weight (p=0.99), or body mass index (p=0.29) on whether the patient experienced a noisy hip. CONCLUSION: No patient factor associated with noise could be identified. It is suggested that this issue be discussed preoperatively with all patients. In our cohort, this would satisfy the majority of patients' wishes and may additionally serve as important evidence in a malpractice claim. Therefore, it is suggested that the British Orthopaedic Association include 'the possibility of noise' in their consent form for THA. PMID- 26854044 TI - Effectiveness of closed suction drainage tip culture in hip arthroplasty. AB - OBJECTIVE: The aim of the present study was to investigate the correlation between bacterial growth in closed suction drainage tip culture and periprosthetic joint infection (PJI). METHODS: Retrospective review included 256 patients who had undergone hip arthroplasty in which the closed suction drainage tip was cultured. Follow-up periods were longer than a year. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated in order to determine the significance of closed suction drainage tip culture in early diagnosis of infection. Patients with positive culture test were monitored to determine the effect of change in antibiotics on treatment of early infection. RESULTS: Eight of the 13 infections showed positive results from closed suction drainage tip culture. Eleven of the 243 non-infectious cases showed positive results after closed suction drainage tip culture (p<0.001). Sensitivity of closed suction drainage tip culture was 61.5%, with a specificity of 95.5%. Positive and negative predictive values were 42.1% and 97.9%, respectively. Systemic antibiotics were administered according to in vitro sensitivity of bacteria cultured from closed suction drainage tip in 13 of 19 positive culture cases. No statistically significant difference in infection risk was observed between the antibiotics group and the group to which antibiotics were not administered (p=0.51). CONCLUSION: Closed suction drainage tip culture can aid in the early detection of infection. PMID- 26854045 TI - Clinical examination of anterior cruciate ligament rupture: a systematic review and meta-analysis. AB - OBJECTIVE: The purpose of this study was to evaluate the sensitivity and specificity of 3 tests for assessing anterior cruciate ligament (ACL) ruptures. METHODS: MEDLINE, EMBASE, Cochrane Library, and CBM (Chinese Biomedical Literature Database) searches were performed. Studies selected for data extraction were those that addressed the accuracy of at least 1 physical diagnostic test for ACL rupture in comparison with a clinical reference standard such as arthroscopy, arthrotomy, or magnetic resonance imaging (MRI). The references of the included studies were also reviewed. Searches were limited to English and Chinese languages. RESULTS: Sixteen studies that assessed the accuracy of the 3 tests for diagnosing ACL ruptures met the inclusion criteria. Study results were, however, heterogeneous. The Lachman test is the most sensitive test to determine ACL tears, showing a pooled sensitivity of 87.1% (95% confidence interval [CI] 0.84-0.90). The pivot shift test is the most specific test, showing a pooled specificity of 97.5% (95% CI 0.95-0.99); additionally, it has the highest positive likelihood ratios (LR+) of 16.00 (95% CI 7.34-34.87). The Lachman test has the lowest negative likelihood ratios (LR-) of 0.17 (95% CI 0.11-0.25). CONCLUSION: In cases of suspected ACL injury, it is recommended to perform the pivot shift test, as it is highly specific and has greater likelihood and discrimination of accurately diagnosing ACL rupture. The Lachman test has great efficacy in ruling out a diagnosis of ACL rupture because of the lowest negative likelihood ratios. PMID- 26854046 TI - Comminution plays no role in worsening fracture healing of conservatively treated middle third clavicular fractures. AB - OBJECTIVE: Middle third clavicular fracture is effectively treated by conservative means. Previous studies showed that comminution and displacement of clavicular fractures might affect fracture healing. However, the clavicle horizontally aligns in the shoulder girdle and has different biomechanics from vertical weight-bearing bones. Therefore, this study was conducted with the hypothesis that comminution has no effect in worsening fracture healing and union configurations in conservatively treated middle third clavicular fractures. METHODS: One hundred ninety-eight middle third clavicular fractures treated by conservative means were reviewed and divided into 2 groups. Group 1, simple fractures, included 97 patients. Group 2, comminuted fractures, included 101 patients. Patient demographic data, initial fracture deformities, and union configurations such as angulation, overlying, and displacement were measured. Union rate and union complications such as delayed nonunion were evaluated. Data were analyzed for statistically significant differences (p<0.05). RESULTS: Initial deformities of Group 1 and Group 2 were 11.94 degrees +/-9.59 degrees and 9.40 degrees +/-8.57 degrees angulation, 12.24+/-12.96 and 11.76+/-10.06 mm of overlying, and 13.31+/-8.63 and 13.72+/-7.42 mm of displacement, respectively, and exhibited no significant differences (p>0.05). Union rate and union complications of Group 1 were 74/97 (76.29%) and 23/97 (23.71%), respectively. For Group 2, the rates were 82/101 (81.19%) and 19/101 (18.81%), respectively. Union configuration of Group 1 and Group 2 were 13.76 degrees +/-10.63 degrees and 12.80 degrees +/-8.65 degrees angulation, 11.93+/-10.75 and 11.52+/-9.38 mm of overlying, and 9.79+/-8.33 and 10.74+/-6.68 mm of displacement, respectively, and showed no significant differences between the groups. CONCLUSION: Comminution plays no role in worsening fracture healing of conservatively treated middle third clavicular fractures in terms of healing rate, union complications, and union configurations. PMID- 26854047 TI - Intracompartmental pressure changes after anterolateral bridge plating of tibial fractures. AB - OBJECTIVE: Compartment syndrome is one of the most devastating complications in orthopedics both for the patient and the treating physician. Among the many causes, trauma and its treatment are the most common reasons for compartment syndrome, which most frequently occurs in the lower leg following tibial fractures. Since bridge plating of difficult metadiaphyseal tibial fractures is becoming increasingly popular, serious concerns have been raised about the increased intracompartmental pressures and possible compartment syndrome. METHODS: This study investigated the intracompartmental pressure changes in anterolateral compartment of the leg during and immediately after anterolateral bridge plating of tibial fractures. Intracompartmental pressures were measured before and during plate application, just after the completion of fixation, and immediately and 4-5 min after the tourniquet release in 22 isolated closed comminuted tibial fractures. RESULTS: Baseline anterolateral compartment pressures were higher than those on the uninjured side (9.3 vs 27.8 mmHg). Pressures were 69.5, 57.4, 65.8, and 56.8 mmHg, respectively, for the other measurements times. None of the patients received prophylactic fasciotomy, and none developed clinical compartment syndrome. CONCLUSION: We found that anterolateral compartmental pressures were higher than pressures on the uninjured side in all patients. Although there is a considerable increase in intracompartmental pressures during and immediately after anterolateral percutaneous bridge plating of comminuted tibial fractures, intraoperative prophylactic fasciotomy is not routinely needed. One should monitor the patients on the first postoperative day for signs of compartment syndrome. Fasciotomy decisions should be based on both clinical symptoms and serial intracompartmental pressure measurements rather than a single measurement. PMID- 26854048 TI - Results of a universal ultrasonographic hip screening program at a single institution. AB - OBJECTIVE: The aims of the present study were to determine the prevalence of developmental dysplasia of the hip (DDH) in newborns screened by hip ultrasonography (US), to review outcome of follow-up and treatment of infants with DDH, and to evaluate the relationship between US-based diagnosis and risk factors. METHODS: A total of 9564 hips of 4782 newborns (2398 females, 50.1%) were evaluated with US. Risk factors for DDH and accompanying deformities were also recorded. Graf classification type IIa(-), IIb, IIc, D, and III hips were treated with Pavlik harnesses. RESULTS: Abnormal US findings (type IIa, IIc, or D hips) were detected in 475 newborns (9.9%). Risk factors and concomitant orthopedic deformities were similar in newborns with and without US abnormality and type I hips (p>0.05 for all). However, abnormal US findings were significantly more common in firstborn and female newborns. A total of 39 hips (5 bilateral, 20 left, 9 right) of 34 newborns (31 females) were placed in Pavlik harnesses. Twelve newborns had type IIc or D hips at initial evaluation, and 22 had type IIb or IIa(-) at follow-up. Mean recovery time was 12.5 (8-16) weeks for newborns with type IIc and D hips, 8.6 (8-12) weeks for those with type IIa(-) hips, and 11.2 (8-12) weeks for those with type IIb hips. CONCLUSION: DDH is still common among newborns in Turkey. Hip US is recommended for detection and follow-up of DDH in newborns. PMID- 26854049 TI - MRI delineation of the morphometric characteristics of type I split cord malformations: a retrospective analysis of 29 cases. AB - OBJECTIVE: The purpose of this study was to elucidate the morphometric characteristics by magnetic resonance imaging (MRI) of type I split cord malformation (SCM) patients. METHODS: All subjects received conventional MRI with the Achieva 3.0T system (Philips Healthcare, Andover, MA, USA), including T1WI/axial and sagittal T2WI/axial FLAIR. Transverse diameter (TD) and sagittal diameter (SD) of the split cord, TD of the convex (TDconvex) and the concave (TDconcave), cranial SD (SDcranial), and caudal SD (SDcaudal) were recorded on the sagittal image combined with the two-dimensional view. Statistical comparison was performed within and between the groups. RESULTS: Twenty-nine type I SCM patients were included, 24 (82.8%) of whom had scoliosis. Mean TD and SD of the split cord were 0.55+/-0.31 cm and 7.52+/-4.03 cm, respectively. No statistically significant difference was observed in TD, SD, and other parameters among the 3 groups. However, mean TD of the split cord in type I SCM patients with congenital scoliosis (0.49+/-0.29 cm) was significantly greater than in those without congenital scoliosis (0.18+/-0.44 cm) (p<0.05). TDconvex was significantly smaller than TDconcave in type I SCM patients with congenital scoliosis (p<0.05). Additionally, there was no statistically significant difference between SDcranial and SDcaudal in type I SCM patients with congenital scoliosis (p>0.05); however, SDcranial was significantly smaller than SDcaudal in Group 2. CONCLUSION: Our study provides the first MRI characterization of the morphometric features of type I SCM, and our findings will help orthopedic surgeons in better navigating the surgical field in corrective surgery of congenital scoliosis of type I SCM patients. PMID- 26854050 TI - Adult spinal deformity: a very heterogeneous population of patients with different needs. AB - OBJECTIVE: The purpose of this study was to analyze and demonstrate the heterogeneity in adult spinal deformity (ASD) populations by baseline health related quality of life (HRQL) data. METHODS: ASD was defined as patients over 18 years of age with any of the following: coronal deformity >20 degrees , sagittal vertical axis (SVA) >5 cm, pelvic tilt >25 degrees , or thoracic kyphosis >60 degrees . Three hundred fifty-two patients meeting the above definition of ASD were analyzed for measures of HRQL (Oswestry disability index [ODI], SRS-22 [Scoliosis Research Society-22], and SF-36 [Short form-36 health survey] questionnaires) at presentation. Age groups were defined as 18-40, 40-60, and >60 years. Deformity was analyzed as either degenerative (DS) or idiopathic (IS) (294 patients; 71 degenerative, 223 idiopathic). RESULTS: There were significant differences between age groups--predominantly between the lower age group (18-40) and others--for all HRQL parameters except SRS-22 mental health and SF-36 mental component score. Similarly, HRQL measures for DS and IS deformities were significantly different. Regarding location of main curves, thoracolumbar/lumbar (TL/L) (70.2%) was dominant for the DS group and thoracic (55%) for the IS group. Mean age was 65 years for the DS group and 36 for the IS group, which were significantly different. Radiographic parameters were also significantly different between these groups, with IS patients having more coronal deformity and better sagittal balance. CONCLUSION: ASD patients are very heterogeneous at presentation, depending on age and diagnosis. There is a distinct need to stratify ASD as early and late presentation ASD and/or by diagnosis. Patients with IS deformity may be very different from those with DS deformity, even at time of presentation. These differences must be taken into consideration in treatment of these patients, as well as for the analysis of the results of treatment. PMID- 26854052 TI - Turkish version of the modified Constant-Murley score and standardized test protocol: reliability and validity. AB - OBJECTIVE: The Constant-Murley score (CMS) is widely used to evaluate disabilities associated with shoulder injuries, but it has been criticized for relying on imprecise terminology and a lack of standardized methodology. A modified guideline, therefore, was published in 2008 with several recommendations. This new version has not yet been translated or culturally adapted for Turkish-speaking populations. The purpose of this study was to translate and cross-culturally adapt the modified CMS and its test protocol, as well as define and measure its reliability and validity. METHODS: The modified CMS was translated into Turkish, consistent with published methodological guidelines. The measurement properties of the Turkish version of the modified CMS were tested in 30 patients (12 males, 18 females; mean age: 59.5+/-13.5 years) with a variety of shoulder pathologies. Intraclass correlation coefficients (ICC) were used to estimate test-retest reliability. Construct validity was analyzed with the Turkish version of the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form and Short-Form Health Survey (SF-12). RESULTS: No difficulties were found in the translation process. The Turkish version of the modified CMS showed excellent test-retest reliability (ICC=0.86). The correlation coefficients between the Turkish version of the modified CMS and the ASES, SF-12-physical component score, and SF-12 mental component scores were found to be 0.48, 0.35, and 0.05, respectively. No floor or ceiling effects were found. CONCLUSION: The translation and cultural adaptation of the modified CMS and its standardized test protocol into Turkish were successful. The Turkish version of the modified CMS has sufficient reliability and validity to measure a variety of shoulder disorders for Turkish-speaking individuals. PMID- 26854051 TI - Results of closing wedge osteotomy in the treatment of sagittal imbalance due to ankylosing spondylitis. AB - OBJECTIVE: Ankylosing spondylitis is a systemic disease which affects the axial skeleton and may cause rigid spinal deformities in advanced cases. Clinical and radiological results of patients with ankylosing spondylitis who underwent pedicle subtraction osteotomy (PSO) were evaluated. METHODS: Twelve (3 female, 9 male) patients who were treated for rigid spinal deformities due to ankylosing spondylitis were evaluated. All patients were treated with the same surgical technique, which included PSO and pedicle screw-rod combination. For radiological results, thoracic kyphosis, lumbar lordosis, pelvic parameters (pelvic incidence, sacral inclination, pelvic tilt), and the distance between the central sagittal line (CSVL) and the sacrum were measured from pre- and postoperative radiograms. For functional results, SF-36 and Oswestry Disability Index (ODI) were used. RESULTS: Mean age of the patients was 39.8+/-8.4 years, and mean follow-up was 85.6+/-39.1 months. Mean angle of lordosis was improved from 6.6 degrees +/-13.7 degrees preoperatively to 43.8 degrees +/-8.4 degrees postoperatively (p<0.0001). Mean CSVL was improved from 19.7+/-9.7 cm preoperatively to 7.45+/ 3.8 cm postoperatively (p=0.0005). Mean local angular change around the osteotomy site was 30.2 degrees +/-6.2 degrees . The pelvic parameters were not significantly changed after the surgeries. Mean ODI, SF-36 mental, and SF-36 physical scores were 30.16+/-9.7, 41.2+/-9.9 and 35.3+/-7.1, respectively. CONCLUSION: In patients with rigid sagittal spinal deformities due to ankylosing spondylitis, lumbar lordosis and sagittal balance can be obtained using PSO. PMID- 26854053 TI - Effects of the lower extremity external fixators on the sexual life of males. AB - OBJECTIVE: In tibial fractures, the use of an external fixator (EF) may be associated with sexual dysfunction (SD) in sexually active male patients. We aimed to investigate the influence of EF applied for tibial fracture on the sexual life in male patients. METHODS: We retrospectively evaluated 137 male patients who presented with tibial fractures and underwent surgical intervention with unilateral or circular EF. The patients completed the Brief Sexual Function Inventory (BSFI) form during the interview. We evaluated the incidence of the development of SD and the severity of SD with the use of an EF, and the relation with the type of EF and SD was investigated. The responses were compared with the results of the completed BSFI forms of 119 male patients who were treated with internal fixation (IF) for tibial fractures. RESULTS: In total, 108 patients (mean age, 42.8 years) treated with EF accepted the invitation and filled the form. The score of those patients were worse compared with that of the patients who were treated with IF (p<0.001). Postoperative sexual functions were the same with the preoperative sexual function in 12 patients (11%). However, the postoperative scores were decreased in 96 (89%) patients, which meant that the sexual functioning was impaired. None of the patients reported persistent SD. CONCLUSION: EF in the cruris may impair sexual functions in males. The rate of SD was higher in male patients who were treated with EF. Thus, SD might be associated with physical, psychological, and social limitations caused by EF. PMID- 26854054 TI - Effects of positive end-expiratory pressure on arthroscopic shoulder surgery under general anesthesia. AB - OBJECTIVE: Our study is a prospective, randomized study on patients undergoing arthroscopic shoulder surgery in the beach-chair position to evaluate the effects of positive end-expiratory pressure (PEEP) on hemodynamic stability, providing a bloodless surgical field and surgical satisfaction. METHODS: Fifty patients were divided into two groups. Group I (n=25) had zero end-expiratory pressure (ZEEP) administered under general anesthesia, and group II (n=25) had +5 PEEP administered. During surgery, intraarticular hemorrhage and surgical satisfaction were evaluated on a scale of 0-10. During surgery, at the 5th, 30th, 60th, and 90th minutes and at the end of surgery, heart rate, mean arterial pressure (MAP), and positive inspiratory pressure were recorded. At the end of the surgery, the amount of bleeding and duration of the operation were recorded. RESULTS: In group I, the duration of operation and amount of bleeding were found to be significantly greater than those in group II (p<0.05). The surgical satisfaction score and clarity of the surgical field were found to be significantly lower in group I than in group II (p<0.05). MAP values in group I were significantly lower than those in group II. The SPO2 values in group I were significantly lower than those in group II. CONCLUSION: Adding PEEP to the ventilation parameters of arthroscopic shoulder surgery in the beach-chair position reduces the amount of hemorrhage in the surgical field and thus increases surgical satisfaction without requiring the creation of controlled hypotension. PMID- 26854055 TI - A new femoral nail with single distal locking screw for maximum interfragment rotational stability. AB - OBJECTIVE: One of the problems for interlocking nailing of the femur is interfragment rotation motion, affecting fracture healing. The nails with single distal locking screw are advantageous for decreasing operation time and radiation exposure. We investigated which single distal screw nail is the best for interfragment rotational stability. METHODS: We used a total of 30 composite femurs, ten for each group. We determined interfragment rotational displacement of composite femurs with three types of single distal screw nails (10 interlocking nails, 10 compression nails and 10 Mehmet anti-rotation nails compressed by tube) at 6-Nm external- 6 Nm internal and 10 Nm extern- 6 Nm internal torques, which imitating respectively the level walking and descending stairs, using an axial distraction testing machine and a custom designed rotation apparatus. RESULTS: Between 10 Nm external and 6 Nm internal torques with single distal locking screw, the interfragment rotational displacement in the Mehmet nail compressed by the 8 Nm torque wrench was mean 1.14 mm and 540% less than mean 7.31 mm in interlocking nails and 400% less than 5.72 mm in compression nails compressed by the 2.5 Nm torque wrench. CONCLUSION: The single distal screw Mehmet nail is superior than other single (or even some double) distal screw nails for maximum rotational stability, with no interfragment distraction gap, no superior nail migration, decreased operation time, and less radiation exposure in axially stable transverse and short oblique femur fractures in daily activities like stair descending or level walking. PMID- 26854056 TI - Dorsal apex curve of the proximal ulna. AB - OBJECTIVE: To analyze the apexes and angulations along the curvature in the posterior border of the proximal ulna-termed the "dorsal apex curve" (DAC)-using the computer-aided design software. METHODS: Eight pairs of normal cadaveric ulnae were analyzed. The ulnar Cartesian coordinate system was standardized using a user-defined coordinate systems feature. DAC was defined by the best-fit curvature of serial apexes in the posterior border in axial cross-sections along the ulna, whereas the best-fit curvature was obtained using polynomials interpolation method. DAC apexes in three different planes were determined by calculating the second derivative value of curve function, and subsequently, DAC angulations were calculated. Statistical analysis was performed using analysis of variance with repeated measures with significance level set as 0.001. RESULTS: The average ulnar length was 246+/-15 mm (224-274 mm). The average ratios of dorsal apex, varus apex, and edge point were 23+/-3% (17-27%), 33+/-4% (27-43%), and 10+/-1% (8-13%), respectively, relative to the ulnar length. The average amount of varus, dorsal, hook, and torsion angulation were 167+/-4 degrees (157 172 degrees ), 176+/-1 degrees (175-178 degrees ), 90+/-0 degrees , and 31+/-10 degrees (15-49 degrees ), respectively. We found no significant differences between left and right ulnae or between male and female ulnae. CONCLUSION: Dorsal apexes and angulations are important landmarks for surgeons when applying plates and attempting total elbow replacement surgery. This curve provides valuable information to medical manufacturers for modeling both plates and ulna components of artificial elbow joints. PMID- 26854057 TI - Effects of cilostazol on fracture healing: an experimental study. AB - OBJECTIVE: The aim of this experimental study was to examine the clinical, radiological and histological effects of cilostazol on fracture healing. METHODS: A total of 60 Wistar albino male rats were divided into 2 groups: the study group (cilostazol) and the control group. Under general anesthesia, using a blunt-ended guillotine, standard closed shaft fractures were formed on the 3-point principle in the left femurs. Starting on the same day after the fracture was formed until sacrifice, the study group animals were administered with cilostazol (50 mg/kg/day, oral tablet). An equal number of rats from both control and study groups were sacrificed on the 7th, 14th, and 21st days after fracture formation, and the bone union tissue was examined clinically, radiologically and histologically. RESULTS: The use of cilostazol was not determined to have any significant effect clinically or radiologically on fracture healing (p>0.05). According to the histological findings, at the end of the first week, the amount of union in the cilostazol group was observed to be significantly greater (p<0.05). At the end of the third week, no significant difference was determined between the control and study groups (p>0.05). CONCLUSION: In the long term, cilostazol did not show any positive effect on fracture healing clinically, radiologically or histologically. PMID- 26854058 TI - Clavicle fracture after reverse total shoulder arthroplasty: a case report with literature review. AB - In reverse total shoulder arthroplasty, retensioning of the deltoid muscle is essential for regaining active elevation. However, the procedure remains problematic, in that it may potentially produce complications not only because it is a complex procedure but also because it causes anatomical changes. We experienced a rare case of a 64-year-old woman presenting with non-traumatic clavicle fracture after reverse total shoulder arthroplasty via a deltopectoral approach. In our case, the patient presented with pain in the clavicle area, which worsened during joint movement. Therefore, surgeons should consider the possibility of clavicle fracture in patients presenting with pain in the clavicle area which worsens. PMID- 26854059 TI - Chondromyxoid fibroma of the pubic ramus: a case report and literature review. AB - Chondromyxoid fibromas (CMF) are benign cartilaginous bone tumors which are found most frequently in the metaphyses of long bones. They comprise less than 1% of primary bone neoplasms. We report an interesting incidental case of a 43-year-old woman with a CMF of the left pubic ramus, presenting with complaints of gradual onset of left groin pain over a period of 2 years. According to radiological examination, a malign chondroid bone tumor was excluded, and histopathological examination confirmed the diagnosis of CMF. The patient underwent aggressive curettage and bone grafting 6 years ago. Pelvic bones are encountered as rare localizations for CMFs. Pubic ramus is accepted as an exceptional site for this benign bone tumor of cartilaginous origin. To our knowledge, no any other CMF case in this localization has been reported in the literature. In atypical regions such as the pelvis and pubic ramus, CMF must be considered for differential diagnosis of malign tumors. PMID- 26854060 TI - Congenital bizarre parosteal osteochondromatous proliferation in unusual location and age: a case report. AB - Bizarre parosteal osteochondromatous proliferation (BPOP, also known as Nora's lesion) is a rare, benign, locally aggressive condition defined as osteochondromatous exostosis arising from the bony cortex. BPOP presents predominantly in the 2nd and 3rd decades of life, and commonly arises from the periosteum of metacarpals and metatarses, though rare locations have been reported, including the long bones, the maxillae, the bones of calvaria, and the sesamoids. The case of an osteochondromatous lesion in an infant with an intra abdominal mass arising from the iliac wing, an atypical location of benign solitary lesions, is reported. Benign solitary lesions are exceptional in this age group. The parents of the patient, who was born in term at 3600 grams, discovered a mass in the left groin and observed decreased movement in the lower left extremity. No history of trauma was reported. When the patient was 5 months of age, AP pelvic X-ray, computed tomography, and magnetic resonance imaging revealed a bony mass displacing intra-abdominal organs anteromedially. Biopsy reported an osteocartilaginous lesion with calcified mature cartilaginous fragments surrounded by plasmacytoid, monotone, fibrinoid cells in myxoid background. Differential diagnosis included osteochondroma, osteochondromyxoma, BPOP, fibrocartilaginous mesenchymoma, chondromyxoid fibroma, periosteal chondroma, soft tissue chondroma, myositis ossificans, and juxtacortical chondroma. Biopsy of the resected specimen determined a diagnosis of BPOP. At 6 month postoperative follow-up, neither symptoms nor complaints related to the mass were present. PMID- 26854062 TI - Analysis of terrain effects on the interfacial force distribution at the hand and forearm during crutch gait. AB - Forces transferred to the upper body during crutch use can lead to both short term and long-term injuries, including joint pain, crutch palsy, and over-use injuries. While this force transmission has been studied in controlled laboratory settings, it is unclear how these forces are affected by irregular terrains commonly encountered during community ambulation. The purpose of this study was to determine the effects of walking speed and uneven terrain on the load magnitude, distribution, and rate of loading at the human-crutch contact surfaces. Our results show that the rates of loading were significantly increased with higher walking speeds and while negotiating certain irregular terrains, despite there being no apparent effect on the peak force transmission, suggesting load rate may be a more appropriate metric for assessing terrain effects on crutch gait. Furthermore, irrespective of the type of terrain and walking condition, the largest compressive forces were found to reside in the carpal tunnel region of the hand, and may therefore be a primary contributor to carpal tunnel injury. PMID- 26854061 TI - Extracellular matrix stiffness dictates Wnt expression through integrin pathway. AB - It is well established that extracellular matrix (ECM) stiffness plays a significant role in regulating the phenotypes and behaviors of many cell types. However, the mechanism underlying the sensing of mechanical cues and subsequent elasticity-triggered pathways remains largely unknown. We observed that stiff ECM significantly enhanced the expression level of several members of the Wnt/beta catenin pathway in both bone marrow mesenchymal stem cells and primary chondrocytes. The activation of beta-catenin by stiff ECM is not dependent on Wnt signals but is elevated by the activation of integrin/ focal adhesion kinase (FAK) pathway. The accumulated beta-catenin then bound to the wnt1 promoter region to up-regulate the gene transcription, thus constituting a positive feedback of the Wnt/beta-catenin pathway. With the amplifying effect of positive feedback, this integrin-activated beta-catenin/Wnt pathway plays significant roles in mediating the enhancement of Wnt signal on stiff ECM and contributes to the regulation of mesenchymal stem cell differentiation and primary chondrocyte phenotype maintenance. The present integrin-regulated Wnt1 expression and signaling contributes to the understanding of the molecular mechanisms underlying the regulation of cell behaviors by ECM elasticity. PMID- 26854063 TI - Glutamate E15 and E171 are Hotspots in p60TRP-Related Cancer. AB - RAS protein is a small G protein linked to multiple G protein-coupled receptor (GPCR) signaling cascades and is responsible for various types of cancer, but to this day, Ras is considered "undruggable." Multiple alternative regulators of G protein signaling (RGS) pathways have become the focus of ongoing efforts to identify new cancer therapeutics. We analyzed human cancer genome datasets and describe p60TRP, a recently identified GPCR-associated sorting protein (GPRASP), and its role in various types of cancer. We found that some regions of p60TRP were more prone to specific mutations, with two hotspots for mutations at E15 and E171. PMID- 26854064 TI - Neurofibromatosis as a gateway to better treatment for a variety of malignancies. AB - The neurofibromatoses (NF) are a group of rare genetic disorders that can affect all races equally at an incidence from 1:3000 (NF1) to a log unit lower for NF2 and schwannomatosis. Since the research community is reporting an increasing number of malignant cancers that carry mutations in the NF genes, the general interest of both the research and pharma community is increasing and the authors saw an opportunity to present a novel, fresh approach to drug discovery in NF. The aim of the paper is to challenge the current drug discovery approach to NF, whereby existing targeted therapies that are either in the clinic or on the market for other disease indications are repurposed for NF. We offer a suggestion for an alternative drug discovery approach. In the new approach, selective and tolerable targeted therapies would be developed for NF and later expanded to patients with more complex diseases such as malignant cancer in which the NF downstream pathways are deregulated. The Children's Tumor Foundation, together with some other major NF funders, is playing a key role in funding critical initiatives that will accelerate the development of better targeted therapies for NF patients, while these novel, innovative treatments could potentially be beneficial to molecularly characterized cancer patients in which NF mutations have been identified. PMID- 26854065 TI - microRNA miR-200b affects proliferation, invasiveness and stemness of endometriotic cells by targeting ZEB1, ZEB2 and KLF4. AB - Endometriosis is characterized by growth of endometrial tissue at ectopic locations. Down-regulation of microRNA miR-200b is observed in endometriosis and malignant disease, driving tumour cells towards an invasive state by enhancing epithelial-to-mesenchymal transition (EMT). miR-200b up-regulation may inhibit EMT and invasive growth in endometriosis. To study its functional impact on the immortalized endometriotic cell line 12Z, the stromal cell line ST-T1b, and primary endometriotic stroma cells, a transient transfection approach with microRNA precursors was employed. Expression of bioinformatically predicted targets of miR-200b was analysed by qPCR. The cellular phenotype was monitored by Matrigel invasion assays, digital-holographic video microscopy and flow cytometry. qPCR revealed significant down-regulation of ZEB1 (P < 0.05) and ZEB2 (P < 0.01) and an increase in E-cadherin (P < 0.01). miR-200b overexpression decreased invasiveness (P < 0.0001) and cell motility (P < 0.05). In contrast, cell proliferation (P < 0.0001) and the stemness-associated side population phenotype (P < 0.01) were enhanced following miR-200b transfection. These properties were possibly due to up-regulation of the pluripotency-associated transcription factor KLF4 (P < 0.05) and require attention when considering therapeutic strategies. In conclusion, up-regulation of miR-200b reverts EMT, emerging as a potential therapeutic approach to inhibit endometriotic cell motility and invasiveness. PMID- 26854066 TI - Skin microbiopsy for HPV DNA detection in cutaneous warts. PMID- 26854067 TI - Tracking ink composition on Herculaneum papyrus scrolls: quantification and speciation of lead by X-ray based techniques and Monte Carlo simulations. AB - The writing in carbonized Herculaneum scrolls, covered and preserved by the pyroclastic events of the Vesuvius in 79 AD, was recently revealed using X-ray phase-contrast tomography, without the need of unrolling the sensitive scrolls. Unfortunately, some of the text is difficult to read due to the interference of the papyrus fibers crossing the written text vertically and horizontally. Recently, lead was found as an elemental constituent in the writing, rendering the text more clearly readable when monitoring the lead X-ray fluorescence signal. Here, several hypotheses are postulated for the origin and state of lead in the papyrus writing. Multi-scale X-ray fluorescence micro-imaging, Monte Carlo quantification and X-ray absorption microspectroscopy experiments are used to provide additional information on the ink composition, in an attempt to determine the origin of the lead in the Herculaneum scrolls and validate the postulated hypotheses. PMID- 26854069 TI - Moire superlattices at the topological insulator Bi2Te3. AB - We report on the observation of complex superlattices at the surface of the topological insulator Bi2Te3. Scanning tunneling microscopy reveals the existence of two different periodic structures in addition to the Bi2Te3 atomic lattice, which is found to strongly affect the local electronic structure. These three different periodicities are interpreted to result from a single small in-plane rotation of the topmost quintuple layer only. Density functional theory calculations support the observed increase in the DOS near the Fermi level, and exclude the possibility that strain is at the origin of the observed Moire pattern. Exploration of Moire superlattices formed by the quintuple layers of topological insulators holds great potential for further tuning of the properties of topological insulators. PMID- 26854070 TI - Amino Acid-Based Stabilization of Oxide Nanocrystals in Polar Media: From Insight in Ligand Exchange to Solution 1H NMR Probing of Short-Chained Adsorbates. AB - Ligand exchange is a crucial step between nanocrystal synthesis and nanocrystal application. Although colloidal stability and ligand exchange in nonpolar media are readily established, the exchange of native, hydrophobic ligands with polar ligands is less systematic. In this paper, we present a versatile ligand exchange strategy for the phase transfer of carboxylic acid capped HfO2 and ZrO2 nanocrystals to various polar solvents, based on small amino acids as the incoming ligand. To gain insight in the fundamental mechanism of the exchange, we study this system with a combination of FTIR, zeta potential measurements, and solution (1)H NMR techniques. The detection of surface-associated, small ligands with solution NMR proves challenging in this respect. Tightly bound amino acids are undetectable, but their existence can be proven through displacement with other ligands in titration experiments. Alternatively, we find that methyl moieties belonging to bound species can circumvent these limitations because of their more favorable relaxation properties as a result of internal mobility. As such, our results are not limited to amino acids but to any short-chained ligand and will therefore facilitate the rigorous investigation and understanding of various ligand exchange processes. PMID- 26854068 TI - Sequence analysis of five endogenous plasmids isolated from Lactobacillus pentosus F03. AB - Lactobacillus pentosus F03, a strain isolated from pig intestines in Taiwan, contains multiple endogenous plasmids. We isolated, completely sequenced, and characterized five of the plasmids present in L. pentosus F03 designated as pF03 1 (3282bp), pF03-2 (3293bp), pF03-3 (1787bp), pF03-4 (2138bp), and pF03-5 (1949bp). The replication types of these plasmids were predicted by comparing the features of the replicon nucleotides and the similarity of replication proteins with those of the plasmids of known replication types. The results of basic local alignment search tool analyses indicate that these plasmids, except for pF03-4, belong to different replicating plasmid families. According to replicon and initiator protein analyses, pF03-1, pF03-2, and pF03-3, were determined to belong respectively to the pMV158, pC194/pUB110, and pT181 families of rolling-circle replication plasmids. However, pF03-5 contains the typical features observed in the family of theta-replicating plasmids and belongs to the pUCL287 family of theta-replicating plasmids. PMID- 26854071 TI - High frame-rate resolution of cell division during Candida albicans filamentation. AB - The commensal yeast, Candida albicans, is an opportunistic pathogen in humans and forms filaments called hyphae and pseudohyphae, in which cell division requires precise temporal and spatial control to produce mononuclear cell compartments. High-frame-rate live-cell imaging (1 frame/min) revealed that nuclear division did not occur across the septal plane. We detected the presence of nucleolar fragments that may be extrachromosomal molecules carrying the ribosomal RNA genes. Cells occasionally maintained multiple nucleoli, suggesting either polyploidy, multiple nuclei and/or aneuploidy of ChrR., while the migration pattern of sister nuclei differed between unbranched and branched hyphae. The presented movie challenges and extends previous concepts of C. albicans cell division. PMID- 26854072 TI - Antibiotic related acute kidney injury in patients treated for open fractures. AB - OBJECTIVE: Antibiotic administration during the treatment of open fractures has been shown to reduce infection rates and is considered a critical step in the management of these injuries. The purpose of this study was to determine if aminoglycoside administration during the treatment of open fractures leads to acute kidney injury. METHODS: Patient records at a level I trauma centre were reviewed for adult patients who presented in 2014 with open fractures were screened for inclusion. Patients were excluded with fractures of the phalanges, metatarsals, and metacarpals, with isolated traumatic arthrotomies, or pre existing renal dysfunction. Charts were reviewed for patient age, gender, race, past medical history, medication history, injury severity score, intravenous dye studies and fracture type. Patients were divided into those given cefazolin (Group A) and cefazolin with gentamicin (Group B). Laboratory values were used to determine which patients developed kidney dysfunction as measured using the RIFLE criteria. Wilcoxon-Mann-Whitney test and Chi-square were used to compare interval and categorical variables, respectively. Significance was set at P<0.05. RESULTS: One-hundred and fifty-nine patients met inclusion criteria. Forty-one (25%) patients were given cefazolin alone and 113 (68%) patients were given cefazolin with gentamicin. Ten (18%) patients with Gustilo-Anderson type III fractures were given cefazolin alone and 67 (67%) patients with types I or II fractures were given a cefazolin with gentamicin. Baseline characteristics and risk factors for renal dysfunction did not vary between groups. Two (4.8%) patients in Group A and 5 (4%) patients in Group B developed acute kidney injury (P=0.599). CONCLUSIONS: Gentamicin use during the treatment of open fractures does not lead to increased rates of renal dysfunction when used in patients with normal baseline renal function. PMID- 26854073 TI - Articular osteotomy of the distal humerus and excision of extensive heterotopic ossification. AB - Prior case series of corrective osteotomy of substantial intra-articular malunion after a fracture of the distal humerus described concomitant heterotopic ossification in a subset of patient, but only in mild forms. We present our experience in treating two patients with malunited articular fractures of the distal humerus with extensive heterotopic ossification and near ankylosis where the lateral articular fragments were encased in heterotopic bone. Although osteotomy of articular malunion after distal humeral fracture along with excision of extensive HO is challenging and risky due to potential devitalization of the fragments, articular deterioration during the delay to osteotomy, and recurrence of heterotopic bone among other concerns, restoring articular congruity in these patients using articular fracture fragments extracted from heterotopic ossification can lead to improved function of the elbow. PMID- 26854074 TI - Incidental findings on whole-body trauma computed tomography: Experience at a major trauma centre. AB - INTRODUCTION: The use of total-body computed tomography (CT) scanning in the evaluation of multiply injured patients is increasing, and their liberal use has stirred debate as to the added benefit relative to the risk of radiation exposure and inappropriate use of limited healthcare resources. Findings unrelated to the clinician's reasons for requesting the radiological examination are often uncovered due to the comprehensive nature of the evaluation at a trauma centre. However, some of these findings are outside the expertise of the trauma team who initially organised the scan and this may lead to uncertainty over who is best qualified to follow-up the incidental finding. We aim to evaluate the frequency of incidental findings on whole body trauma CT scans in a consecutive series of trauma admissions to our unit. MATERIALS AND METHODS: We identified 104 consecutive major trauma patients who received a whole-body trauma CT (head, cervical spine, chest, abdomen and pelvis) from Jan 2013 to Dec 2013 in our unit (out of a total of 976 trauma admissions in the same year). Patient-specific information was extracted from computerised hospital databases containing admission and progress notes, radiological reports, operation notes and pathology reports. RESULTS: 57 patients (54.8%) had incidental findings identified on the radiologist report, with a total of 114 individual incidental findings. 6 (5.8%) patients had potentially severe findings that required further diagnostic work up; 65 (62.5%) patients had diagnostic workup dependant on their symptoms, and 43 (41.3%) patients had incidental findings of minor concern which required no follow up. DISCUSSION AND CONCLUSIONS: Our findings reflect the literature noting that incidental findings are increasingly common due to the central diagnostic role of CT imaging in trauma care, but also due to advances in imaging techniques and quality. In keeping with published literature, we note that increased age is associated with an increased incidence of "incidental findings" and this will continue to rise with the ageing population and the mandatory nature of trauma CTs. PMID- 26854075 TI - The incidence, spectrum and outcomes of traumatic bladder injuries within the Pietermaritzburg Metropolitan Trauma Service. AB - INTRODUCTION: The purpose of this study is to provide a comprehensive overview of the incidence, spectrum and outcomes of traumatic bladder injury in Pietermaritzburg, South Africa, and to identify the current optimal investigation and management of patients with traumatic bladder injuries. METHODS: The Pietermaritzburg Metropolitan Trauma Service (PMTS) trauma registry was interrogated retrospectively for all traumatic bladder injuries between 1 January 2012 and 31 October 2014. RESULTS: Of 8129 patients treated by the PMTS over the study period, 58 patients (0.7% or 6.5 cases per 1,000,000 population per year) had bladder injuries, 65% caused by penetrating trauma and 35% by blunt trauma. The majority (60%) were intraperitoneal bladder ruptures (IBRs), followed by 22% extraperitoneal bladder ruptures (EBRs). There was a high rate of associated injury, with blunt trauma being associated with pelvic fracture and penetrating trauma being associated with rectum and small intestine injuries. The mortality rate was 5%. Most bladder injuries were diagnosed at surgery or by computed tomography (CT) scan. All IBRs were managed operatively, as well as 38% of EBRs; the remaining EBRs were managed by catheter drainage and observation. In the majority of operative repairs, the bladder was closed in two layers, and was drained with only a urethral catheter. Most patients (91%) were managed definitively by the surgeons on the trauma service. CONCLUSION: Traumatic bladder rupture caused by blunt or penetrating trauma is rare and mortality is due to associated injuries. CT scan is the investigative modality of choice. In our environment IBR is more common than EBR and requires operative management. Most EBRs can be managed non-operatively, and then require routine follow-up cystography. Simple traumatic bladder injuries can be managed definitively by trauma surgeons. A dedicated urological surgeon should be consulted for complex injuries. PMID- 26854077 TI - (56)Mn, (60)Co, (18)F and (22)Na activity measurements by coincidence technique at VNIIM. AB - For modernization of the Russian national activity standard at the Ionizing Radiation Department of the D.I. Mendeleyev Institute for Metrology, a prototype 4pi(LS)-gamma(NaI) coincidence arrangement was created, and applied to the standardization of long-lived (60)Co and (22)Na and short-lived (56)Mn and (18)F. Efficiency variation was performed using "grey filters", high voltage variation and variation of low threshold. The main metrological characteristics of the setup were determined: long-term stability, background, dead time, resolution time and temperature dependence. The results obtained have practical applications. The (18)F solution with well-known activity is required for calibration of ionizing chamber used in nuclear medicine. The (56)Mn is used for calibration of manganese bath equipment used in neutron laboratory. The results obtained are in good agreement with 4pigamma(NaI)-counting and 4pibeta(PC) gamma(NaI) methods of Russian national radioactivity standard. The combined uncertainty (k=2) of results was estimated in the range 1-2%. PMID- 26854076 TI - Sustained expression of GLP-1 receptor differentially modulates beta-cell functions in diabetic and nondiabetic mice. AB - Glucagon-like peptide 1 (GLP-1) has been shown to play important roles in maintaining beta-cell functions, such as insulin secretion and proliferation. While expression levels of GLP-1 receptor (Glp1r) are compromised in the islets of diabetic rodents, it remains unclear when and to what degree Glp1r mRNA levels are decreased during the progression of diabetes. In this study, we performed real-time PCR with the islets of db/db diabetic mice at different ages, and found that the expression levels of Glp1r were comparable to those of the islets of nondiabetic db/misty controls at the age of four weeks, and were significantly decreased at the age of eight and 12 weeks. To investigate whether restored expression of Glp1r affects the diabetic phenotypes, we generated the transgenic mouse model Pdx1(PB)-CreER(TM); CAG-CAT-Glp1r (betaGlp1r) that allows for induction of Glp1r expression specifically in beta cells. Whereas the expression of exogenous Glp1r had no measurable effect on glucose tolerance in nondiabetic betaGlp1r;db/misty mice, betaGlp1r;db/db mice exhibited higher glucose and lower insulin levels in blood on glucose challenge test than control db/db littermates. In contrast, four weeks of treatment with exendin-4 improved the glucose profiles and increased serum insulin levels in betaGlp1r;db/db mice, to significantly higher levels than those in control db/db mice. These differential effects of exogenous Glp1r in nondiabetic and diabetic mice suggest that downregulation of Glp1r might be required to slow the progression of beta-cell failure under diabetic conditions. PMID- 26854078 TI - Assortativity evolving from social dilemmas. AB - Assortative mechanisms can overcome tragedies of the commons that otherwise result in dilemma situations. Assortativity criteria include various forms of kin selection, greenbeard genes, and reciprocal behaviors, usually presuming an exogenously fixed matching mechanism. Here, we endogenize the matching process with the aim of investigating how assortativity itself, jointly with cooperation, is driven by evolution. Our main finding is that full-or-null assortativities turn out to be long-run stable in most cases, independent of the relative speeds of both processes. The exact incentive structure of the underlying social dilemma matters crucially. The resulting social loss is evaluated for general classes of dilemma games, thus quantifying to what extent the tragedy of the commons may be endogenously overcome. PMID- 26854079 TI - Increased concentration of plasma TNFR1 and TNFR2 in paediatric lupus nephritis. AB - BACKGROUND: Juvenile-onset systemic lupus erythematous (JSLE) is a debilitating condition that frequently involves the kidneys (lupus nephritis; LN). Tumour necrosis factor alpha (TNF-alpha), an important pro-inflammatory cytokine, is expressed locally in the kidney and correlates with LN disease activity. The aim of this study was to ascertain whether soluble receptors for TNF-alpha (sTNFR1/sTNFR2) are significantly increased in children with LN. METHODS: Plasma samples were collected from JSLE patients at routine review. Concentrations of sTNFR1 and sTNFR2 were measured (median; interquartile range, IQR) using enzyme linked immunosorbent assay (ELISA) in 25 JSLE patients (seven LN) and 20 healthy controls (HCs). RESULTS: sTNFR2 concentration was significantly increased in JSLE (5149 pg/dl, 3413-8561) compared to HCs (3858 pg/dl, 2254-5165; p = 0.049). sTNFR1 concentration was significantly increased in active LN (n = 7, 1765 pg/dl, IQR 1133-4167) compared to inactive LN (n = 18, 1104 pg/dl, 886-1272; p = 0.018). There was a non-significant increase in sTNFR2 concentration in active LN (9829 pg/dl, 3298-21271) compared to inactive LN (4595 pg/dl, 3345-6993; p = 0.146). sTNFR1 concentration correlated moderately with sTNFR2 (r = 0.66, p < 0.001). sTNFR2 demonstrated strong positive correlations with ESR (r = 0.941, p < 0.01) and anti-dsDNA antibodies (r = 0.998, p = 0.041). Both receptors also positively correlated with creatinine (TNFR1 r = 0.81, p < 0.001; TNFR2 r = 0.50, p = 0.015) and urinary albumin creatinine ratio (TNFR1 r = 0.64, p < 0.01; TNFR2 r = 0.63, p < 0.01). CONCLUSIONS: These data indicate that sTNFR1 and sTNFR2 concentrations are elevated in LN and may reflect renal activity. These results provide basis for further investigation into the pathological pathways underlying LN. PMID- 26854080 TI - Three cases of spondyloenchondrodysplasia (SPENCD) with systemic lupus erythematosus: a case series and review of the literature. AB - Spondyloenchondrodysplasia (SPENCD) is a rare autosomal recessive skeletal dysplasia caused by recessive mutations in the ACP5 gene, and it is characterized by the persistence of chondroid tissue islands within the bone. The clinical spectrum of SPENCD includes neurological involvement and immune dysfunction, such as systemic lupus erythematosus (SLE). To date, there are only 12 reported cases of SPENCD associated with SLE in the literature; however, detailed clinical follow-up data is absent for this comorbidity. This report presents clinical and laboratory data of three patients diagnosed with SPENCD-associated SLE. All three patients had short stature, arthralgia/arthritis, lupus nephritis, hypocomplementemia, and positive autoantibodies, including anti-nuclear and anti dsDNA antibodies. Two patients exhibited class IV and one patient exhibited class V lupus nephritis. The early recognition of SPENCD is imperative, and this condition should be considered in patients with SLE, particularly in individuals with short stature and skeletal abnormalities. The cases presented here demonstrate that timely diagnosis and follow-up are key factors for the successful management of these conditions. PMID- 26854081 TI - Endometriosis and systemic lupus erythematosus: a population-based case-control study. AB - OBJECTIVE: To investigate the association between endometriosis and systemic lupus erythematosus (SLE) in prospectively collected population-based data. METHODS: We conducted a case-control study using Swedish registers, identifying female SLE cases from the National Patient Register and female controls sampled from the general population matched on birth year, sex and county during 1964 2011. We identified endometriosis diagnoses from the National Patient Register using ICD codes. We estimated odds ratios and 95% confidence intervals using conditional logistic regression models. RESULTS: We identified 2834 cases of SLE and 14,164 controls. Seventy-eight cases were diagnosed with endometriosis prior to their SLE diagnosis and 288 controls were diagnosed prior to the index date. We observed a significant association between endometriosis and subsequent SLE with an odds ratio of 1.39 (95% confidence interval = 1.09-1.78). The association was similar when requiring a laparoscopy/laparotomy within six months of the endometriosis diagnosis (odds ratio = 1.33; 95% confidence interval = 0.84-2.12) while the association was stronger when restricted to endometriosis diagnosed at the same time as hysterectomy (odds ratio = 2.26; 95% confidence interval = 1.47 3.64). CONCLUSIONS: Our findings suggest an association between endometriosis and SLE. Future prospective studies with extended follow-up will be necessary to clarify whether this association is influenced by the timing and severity of endometriosis diagnosis. PMID- 26854082 TI - Evaluating the Use of Plain Language in a Cancer Clinical Trial Website/App. AB - Medically complex titles and descriptions found on clinical trial websites and online applications present a barrier to comprehension for users from the general public. In this study, we examine the effectiveness of plain language trial descriptions for user comprehension of basic trial details. Two hundred seventeen volunteers recruited from patient waiting areas completed 441 user tests of ten plain language trial descriptions. The majority of volunteers adequately comprehended the cancer type and basic inclusion/exclusion criteria from plain language trial descriptions. Difficulty comprehending the treatment being studied was seen in seven of ten descriptions tested. Revision and retesting of the seven trial descriptions showed continued user challenges in comprehending the treatment being studied. Plain language clinical trial descriptions integrated into a website/app allowed users to understand basic inclusion/exclusion criteria. Despite plain language used, discerning the treatment being studied may be difficult for some users. Integration of plain language descriptions into clinical trial online applications can help users understand trial basics. Further research regarding effective use of plain language to communicate the treatment being studied is needed. PMID- 26854083 TI - Overview of Cancer Prevention and Control and African-Americans. PMID- 26854085 TI - Interplay of the histone methyltransferases SDG8 and SDG26 in the regulation of transcription and plant flowering and development. AB - Histone methylations play fundamental roles in epigenetic regulation of transcription in many eukaryotes. In the model plant Arabidopsis thaliana as in human, a same histone lysine residue (e.g. H3K4 or H3K36) can be a potential target substrate for various different histone lysine methyltransferases (HKMTs). Using powerful genetic tool in Arabidopsis, we here investigate the interplay between two close HKMT homologues, SET DOMAIN GROUP 8 (SDG8) and SDG26, in regulating transcription and plant growth and development. We show that the sdg8 mutation is epistatic to the sdg26 one, leading to a sdg8 sdg26 double mutant exhibiting defects similar to sdg8 (reduced level of H3K36me3, increased level of H3K36me1, reduced plant body size, early flowering associated with reduced expression of FLC and MAFs and increased expression of FT and SOC1), but opposite to sdg26 (increased rosette size, late flowering associated with increased FLC and MAF5 expression and reduced FT and SOC1 expression). In parallel to the finding of the epistasis of SDG8, our study also unravels novel functions of SDG26 in H3K36me1 deposition and in the interplay with SDG8 in regulating the genome-wide gene expression. The implication of various HKMTs in establishing different forms of histone methylation and gene-context-specific chromatin modifications likely provides an advantageous mechanism for the regulation of transcription to cope with complex and plastic growth and developmental programs in plants and possibly also in other organisms. PMID- 26854084 TI - Who Is a Cancer Survivor? A Systematic Review of Published Definitions. AB - The term "cancer survivor" is commonly used by different persons, clinical institutions, academic bodies, and political organizations although it lacks of a unanimous and detailed definition. The objective of the study is to make a systematic review of published and proposed definitions of "cancer survivor." Utilizing a systematic search strategy with different strings of "cancer survivor," we searched the following databases: Medline (June 1975-June 2015), Scopus (all the years), Web of Science (all the years), Google Scholar (all the years), ERIC (all the years). This review suggests that there is not a unique definition of who is a "cancer survivor" and what is "cancer survivorship." However, the most widely used definition sees cancer survivorship as a process that begins at the moment of diagnosis and continues through the balance of life. This definition highlights psychological and legal patient's needs-as well as medical ones-to receive care and assistance from the beginning and, at the same time, it establishes valid criteria for making scientific and statistical sampling research. The extensive use of the term "cancer survivor" indicates that it is a significant term. This review has been written to outline the state of the art and it invites to reflect on a shared definition that could satisfy both clinical and research aspects. Implication for cancer survivors: this compendium of proposed definitions may improve communication among the many patients and patient organizations that use and work with this term. PMID- 26854086 TI - BAP1 is overexpressed in black compared with white patients with Mx-M1 clear cell renal cell carcinoma: A report from the cancer genome atlas. AB - OBJECTIVES: Incidence of renal cell carcinoma (RCC) is higher in Black patients with disease-specific and overall survival being lower compared with White patients even though renal tumors among Black patients are more likely to be localized. These disparities have been attributed to higher rates of obesity and hypertension, lower rates of nephrectomy, and a lack of access to quality health care. With scant genomic evidence to account for these disparities, the present study sought to compare BAP1 expression between Black and White patients with clear cell RCC (ccRCC); a gene that inhibits tumor progression when overexpressed and results in poor clinical outcomes when silenced. MATERIALS AND METHODS: The cancer genome atlas dataset was used to identify 58 (9.9%) Black and 529 (90.9%) White patients with ccRCC with an initial pathologic diagnosis from 1998 to 2013. BAP1 expression was compared using a Mann-Whitney U test. The association between BAP1 expression and pathologic stage, American Joint Committee on Cancer (AJCC) stage, and Fuhrman grade was assessed for the overall cohort and stratified by race. The association between BAP1 expression and overall survival was assessed using Cox proportion hazards models adjusting for Fuhrman grade, pathologic stage, and the presence of pathologic metastases for the overall cohort and stratified by race. RESULTS: The level of BAP1 expression was significantly higher in Black vs. White patients with ccRCC (10.5 vs. 10.3; P<.001). For the overall cohort, increasing BAP1 expression was associated with decreasing pathologic stage (beta =-0.25, P = .004) and decreasing AJCC stage (beta =-0.029, P = .006). For Black patients, increasing BAP1 expression was associated with decreasing AJCC stage (beta =-0.79, P = .016), decreasing Fuhrman grade (beta = 0.55, P = .011), and a decreased risk of pathologic metastases (odds ratio [OR] = 0.83, P = .038). For White patients, increasing BAP1 expression was associated with decreasing pathologic stage (beta =-0.20, P = .026). CONCLUSIONS: BAP1 is significantly overexpressed in Black compared with White patients and is associated with favorable stage. BAP1 overexpression portends distinct pathologic outcomes in Black and White patients demonstrating the need for racial stratification and adequate Black patient sampling in BAP1 biomarker studies. PMID- 26854087 TI - Snakes elicit earlier, and monkey faces, later, gamma oscillations in macaque pulvinar neurons. AB - Gamma oscillations (30-80 Hz) have been suggested to be involved in feedforward visual information processing, and might play an important role in detecting snakes as predators of primates. In the present study, we analyzed gamma oscillations of pulvinar neurons in the monkeys during a delayed non-matching to sample task, in which monkeys were required to discriminate 4 categories of visual stimuli (snakes, monkey faces, monkey hands and simple geometrical patterns). Gamma oscillations of pulvinar neuronal activity were analyzed in three phases around the stimulus onset (Pre-stimulus: 500 ms before stimulus onset; Early: 0-200 ms after stimulus onset; and Late: 300-500 ms after stimulus onset). The results showed significant increases in mean strength of gamma oscillations in the Early phase for snakes and the Late phase for monkey faces, but no significant differences in ratios and frequencies of gamma oscillations among the 3 phases. The different periods of stronger gamma oscillations provide neurophysiological evidence that is consistent with other studies indicating that primates can detect snakes very rapidly and also cue in to faces for information. Our results are suggestive of different roles of gamma oscillations in the pulvinar: feedforward processing for images of snakes and cortico-pulvinar cortical integration for images of faces. PMID- 26854088 TI - Performance comparison of biofilm and suspended sludge from a sequencing batch biofilm reactor treating mariculture wastewater under oxytetracycline stress. AB - The performance, extracellular polymeric substances (EPS) and microbial community of a sequencing batch biofilm reactor (SBBR) were investigated in treating mariculture wastewater under oxytetracycline stress. The chemical oxygen demand and [Formula: see text]-N removal efficiencies of the SBBR decreased with the increase of oxytetracycline concentration, and no obvious [Formula: see text]-N and [Formula: see text]-N accumulation in the effluent appeared at less than 10 mg L(-1) oxytetracycline. The specific oxygen utilization rate of the suspended sludge was more than that of the biofilm at different oxytetracycline concentrations. The specific ammonium oxidation rate (SAOR) of the biofilm was more easily affected by oxytetracycline than that of the suspended sludge, whereas the effect of oxytetracycline on the specific nitrite oxidation rate (SNOR) of the biofilm was less than that of the suspended sludge. The specific nitrate reduction rate of both the biofilm and suspended sludge was higher than the sum of the SAOR and SNOR at different oxytetracycline concentrations. The protein and polysaccharide contents in the EPS of the biofilm and suspended sludge increased with the increase of oxytetracycline concentration. The appearance of oxytetracycline in the influent could affect the chemical composition of the loosely bound EPS and tightly bound EPS. The amino, carboxyl and hydroxyl groups might be involved with interaction between EPS and oxytetracycline. The denaturing gradient gel electrophoresis profiles indicated that the variation of oxytetracycline concentration in the influent could affect the microbial communities of both the biofilm and suspended sludge. PMID- 26854090 TI - Toward the First Data Acquisition Standard in Synthetic Biology. AB - This paper describes the development of a new data acquisition standard for synthetic biology. This comprises the creation of a methodology that is designed to capture all the data, metadata, and protocol information associated with biopart characterization experiments. The new standard, called DICOM-SB, is based on the highly successful Digital Imaging and Communications in Medicine (DICOM) standard in medicine. A data model is described which has been specifically developed for synthetic biology. The model is a modular, extensible data model for the experimental process, which can optimize data storage for large amounts of data. DICOM-SB also includes services orientated toward the automatic exchange of data and information between modalities and repositories. DICOM-SB has been developed in the context of systematic design in synthetic biology, which is based on the engineering principles of modularity, standardization, and characterization. The systematic design approach utilizes the design, build, test, and learn design cycle paradigm. DICOM-SB has been designed to be compatible with and complementary to other standards in synthetic biology, including SBOL. In this regard, the software provides effective interoperability. The new standard has been tested by experiments and data exchange between Nanyang Technological University in Singapore and Imperial College London. PMID- 26854089 TI - Clinically relevant variants identified in thoracic aortic aneurysm patients by research exome sequencing. AB - Thoracic aortic aneurysm (TAA) is a genetically heterogeneous disease involving subclinical and progressive dilation of the thoracic aorta, which can lead to life-threatening complications such as dissection or rupture. Genetic testing is important for risk stratification and identification of at risk family members, and clinically available genetic testing panels have been expanding rapidly. However, when past testing results are normal, there is little evidence to guide decision-making about the indications and timing to pursue additional clinical genetic testing. Results from research based genetic testing can help inform this process. Here we present 10 TAA patients who have a family history of disease and who enrolled in research-based exome testing. Nine of these ten patients had previous clinical genetic testing that did not identify the cause of disease. We sought to determine the number of rare variants in 23 known TAA associated genes identified by research-based exome testing. In total, we found 10 rare variants in six patients. Likely pathogenic variants included a TGFB2 variant in one patient and a SMAD3 variant in another. These variants have been reported previously in individuals with similar phenotypes. Variants of uncertain significance of particular interest included novel variants in MYLK and MFAP5, which were identified in a third patient. In total, clinically reportable rare variants were found in 6/10 (60%) patients, with at least 2/10 (20%) patients having likely pathogenic variants identified. These data indicate that consideration of re-testing is important in TAA patients with previous negative or inconclusive results. PMID- 26854091 TI - [Oral viral infections]. AB - Exclude herpes infection in the presence of acute oral ulcers of unknown origin, particularly in patients in poor general condition. Remember that asymptomatic HSV-1 shedding in saliva may result in an oral-genital transmission. Perform an anogenital examination and a screening for other sexually transmitted diseases when oral warts are diagnosed. Search for immunosuppression and monitor the patient (screening for a potential associated carcinoma) when there is rapid growth of oral warts. Consider all the clinical signs (systemic, skin, other mucosa, immunity...) when a patient has an enanthem or oral ulcerations. Ask for a HIV test when an oral Kaposi's sarcoma, a hairy leukoplakia or major aphthae are diagnosed. PMID- 26854093 TI - [Food-cobalamin malabsorption and vitamin B12 deficiency in adults and in elderly patients: What is the problem?]. PMID- 26854092 TI - Theoretical explanations for maintenance of behaviour change: a systematic review of behaviour theories. AB - BACKGROUND: Behaviour change interventions are effective in supporting individuals in achieving temporary behaviour change. Behaviour change maintenance, however, is rarely attained. The aim of this review was to identify and synthesise current theoretical explanations for behaviour change maintenance to inform future research and practice. METHODS: Potentially relevant theories were identified through systematic searches of electronic databases (Ovid MEDLINE, Embase, PsycINFO). In addition, an existing database of 80 theories was searched, and 25 theory experts were consulted. Theories were included if they formulated hypotheses about behaviour change maintenance. Included theories were synthesised thematically to ascertain overarching explanations for behaviour change maintenance. Initial theoretical themes were cross-validated. FINDINGS: One hundred and seventeen behaviour theories were identified, of which 100 met the inclusion criteria. Five overarching, interconnected themes representing theoretical explanations for behaviour change maintenance emerged. Theoretical explanations of behaviour change maintenance focus on the differential nature and role of motives, self-regulation, resources (psychological and physical), habits, and environmental and social influences from initiation to maintenance. DISCUSSION: There are distinct patterns of theoretical explanations for behaviour change and for behaviour change maintenance. The findings from this review can guide the development and evaluation of interventions promoting maintenance of health behaviours and help in the development of an integrated theory of behaviour change maintenance. PMID- 26854094 TI - Adult acute lymphoblastic leukemia with a rare b3a3 type BCR/ABL1 fusion transcript. AB - The Philadelphia chromosome (Ph) is the most frequent chromosomal abnormality detected in adult acute lymphoblastic leukemia (ALL). This chromosome forms the BCR/ABL1 fusion gene; thus, ABL1 exon a2 is generally used as a primer-binding region for the detection of the fusion transcript via reverse transcription polymerase chain reaction (RT-PCR). We observed a rare case of adult Ph-positive (Ph(+)) ALL, in which the BCR/ABL1 fusion transcript was not detected using the ABL1 exon a2 region primer. However, we were able to isolate a PCR product by RT PCR with the BCR exon 13 (b2) and ABL1 exon a3 primers. Analysis of the sequence of the RT-PCR product revealed that the fusion point was between BCR exon 14 (b3) and ABL1 exon a3, and that the transcript lacked ABL1 exon a2. The patient achieved cytogenetic remission through combination chemotherapies, but relapse occurred before hematopoietic stem cell transplantation and the patient died 11 months after the initialization of chemotherapies. If the BCR/ABL1 fusion transcript is undetected with the ABL1 exon a2 region primer in Ph(+) ALL cases, an RT-PCR analysis that can detect the b3a3 type BCR/ABL1 fusion transcript should be considered to improve diagnosis. PMID- 26854095 TI - Tuning and predicting the wetting of nanoengineered material surface. AB - The wetting of a material can be tuned by changing the roughness on its surface. Recent advances in the field of nanotechnology open exciting opportunities to control macroscopic wetting behaviour. Yet, the benchmark theories used to describe the wettability of macroscopically rough surfaces fail to fully describe the wetting behaviour of systems with topographical features at the nanoscale. To shed light on the events occurring at the nanoscale we have utilised model gradient substrata where surface nanotopography was tailored in a controlled and robust manner. The intrinsic wettability of the coatings was varied from hydrophilic to hydrophobic. The measured water contact angle could not be described by the classical theories. We developed an empirical model that effectively captures the experimental data, and further enables us to predict the wetting of surfaces with nanoscale roughness by considering the physical and chemical properties of the material. The fundamental insights presented here are important for the rational design of advanced materials having tailored surface nanotopography with predictable wettability. PMID- 26854096 TI - Interfacial tension and a three-phase generalized self-consistent theory of non dilute soft composite solids. AB - In the dilute limit Eshelby's inclusion theory captures the behavior of a wide range of systems and properties. However, because Eshelby's approach neglects interfacial stress, it breaks down in soft materials as the inclusion size approaches the elastocapillarity length L=gamma/E. Here, we use a three-phase generalized self-consistent method to calculate the elastic moduli of composites comprised of an isotropic, linear-elastic compliant solid hosting a spatially random monodisperse distribution of spherical liquid droplets. As opposed to similar approaches, we explicitly capture the liquid-solid interfacial stress when it is treated as an isotropic, strain-independent surface tension. Within this framework, the composite stiffness depends solely on the ratio of the elastocapillarity length L to the inclusion radius R. Independent of inclusion volume fraction, we find that the composite is stiffened by the inclusions whenever R < 3L/2. Over the same range of parameters, we compare our results with alternative approaches (dilute and Mori-Tanaka theories that include surface tension). Our framework can be easily extended to calculate the composite properties of more general soft materials where surface tension plays a role. PMID- 26854097 TI - Metamizole: an effective solution for vasospasm. AB - OBJECTIVE: Vasospasm is a major problem during microsurgery, and a variety of pharmacological agents are used to alleviate vasospasm. This study aimed to demonstrate the effect of metamizole on vasospasm and to compare it with lidocaine and papaverine, both of which are commonly used to correct vasospasm. METHODS: Thirty-five female rats were randomly divided into four groups: Group 1, 2, 3, and 4, which were the control (n = 8), metamizole (n = 9), papaverine (n = 9), and lidocaine (n = 9) treatment groups, respectively. Both femoral arteries of all of the rats were dissected, and they were immediately photographed. The pharmacological agents or saline in the control group were topically applied to the arteries, accordingly. The arteries were photographed again at time points 5, 10, 20 and 30 minutes after application of the agents. The images were transferred to a computer and the arteries' diameters were measured in mm. RESULTS: All of the pharmacological treatments increased the diameter of the arteries significantly during the observation period. However, comparison between the groups indicated that metamizole and papaverine produced significantly more vasodilation than the lidocaine group, for all time points measured after application. CONCLUSION: These findings show that topically applied metamizole is as effective as papaverine at alleviating vasospasm during the 30 minutes time interval. This administration may be considered as a good alternative to correct vasospasm during microsurgery. PMID- 26854098 TI - Did the Iceman Know Better? Screening of the Medicinal Properties of the Birch Polypore Medicinal Mushroom, Piptoporus betulinus (Higher Basidiomycetes). AB - The birch polypore Piptoporus betulinus was among two mushrooms that were found in the Iceman's bag. Recent studies indicated that P. betulinus was probably used as a religious and medicinal item. In order to examine the medicinal potential of P. betulinus, hot water (HW), partially purified (PP), and alkali extract (HA) were prepared and tested for antioxidant, antimicrobial, cytotoxic, and angiotensin I-converting enzyme (ACE) inhibitory activity. All tested samples exhibited moderate cytotoxic activity, and HW appeared as the most effective (IC50 = 0.8 +/- 0.1 mg/ml for HeLa cells). HA proved to be a good 1,1-diphenyl-2 picrylhydrazyl radical scavenger and exhibited the strongest ferric-reducing power (EC50 = 0.07 +/- 0.3 mg/ml). The same extract (HA) also expressed the strongest ferric-reducing power (EC50 = 0.99 +/- 0.1 mg/ml). Hot alkali extraction contributed significantly to ACE inhibitory activity (EC50 = 0.06 +/- 0.00 mg/ml) and to antimicrobial activity, especially against highly resistant Enterococcus faecalis (minimum inhibitory concentration: 0.156 +/- 0.000 mg/ml; and minimum bactericidal concentration: 1.25 +/- 0.00 mg/ml). PMID- 26854099 TI - The Shaggy Ink Cap Medicinal Mushroom, Coprinus comatus (Higher Basidiomycetes) Extract Induces Apoptosis in Ovarian Cancer Cells via Extrinsic and Intrinsic Apoptotic Pathways. AB - In a previous study, ethyl acetate extract of Coprinus comatus was found to reduce viability of human ovarian cancer cells. The objective of the current research was to clarify the mechanism of action of this extract. Ovarian cancer cells (ES-2) were subjected to ethyl acetate extract of C. comatus for different concentrations or exposure times. Cell cycle analysis and annexin V staining were performed using an automated flow cytometer. DNA fragmentation was detected using the TUNEL assay. Western blot analysis was performed for the assessment of activation of caspases -3, -8, and -9. Results revealed that treatment of ES-2 cells with ethyl acetate extract of C. comatus (100 MUg/ml medium), for 48 h or for 72 h resulted in an increased number of cells at the sub-G1 phase of the cell cycle. These treatments also resulted in an increased number of apoptotic cells (positively stained by annexin and positively labeled by TUNEL), in comparison to the control. Reduced levels of procaspases -3, -8, and-9 were also detected in treated cells. In conclusion, ethyl acetate extract of C. comatus induces apoptosis in ovarian cancer cells (ES-2), via both extrinsic and intrinsic pathways. Meanwhile, more investigations are needed to demonstrate weather the apoptotic effect on ovarian cancer cells is accomplished by one active compound, or combined activities of different compounds that exist in the extract. PMID- 26854100 TI - Protective Effects of Extract from Sclerotium of the King Tuber Medicinal Mushroom, Pleurotus tuberregium (Higher Basidiomycetes) on Carbon Tetrachloride Induced Hepatotoxicity in Wistar Albino Rats. AB - This study was undertaken to investigate the effect of 50% ethanol extract from the sclerotia of Pleurotus tuberregium on hepatocellular integrity of albino rats treated with carbon tetrachloride (CCl4). Activities of hepatic enzymes alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) were determined in serum. Antioxidant enzyme activities, total protein, and level of malondialdehyde (MDA) were assayed in liver homogenate from treated rats. Oral administration of CCl4 (2 ml/kg body weight/day) for 7 consecutive days caused hepatotoxicity. There was a significant increase in the activity of serum ALT, AST, and ALP and the level of MDA in the liver. However, the activities of catalase and superoxide dismutase, which are antioxidant enzymes, were significantly reduced (p < 0.05). Concomitant treatment with 250 mg/kg body weight of extract and CCl4 for 7 consecutive days resulted in a significant decrease in the activity of liver marker enzymes [46% (ALT), 67.25% (AST), and 68.51% (ALP)]. These activities were further decreased [68.24% (ALT), 78.39% (AST), and 75.38% (ALP)] when the extract was increased to 500 mg/kg body weight. The activities of antioxidant enzymes, total protein, and MDA content of the liver were improved to levels that are not significantly different from the control. These findings, therefore, suggest that ethanol extract from the sclerotia of P. tuberregium has a protective action against CCl4-induced hepatotoxicity. PMID- 26854101 TI - Antiproliferative Activity of Some Higher Mushrooms from Hungary against Human Cancer Cell Lines. AB - In the present work, aqueous and organic extracts of 16 Basidiomycetes mushrooms and 1 Ascomycetes mushroom were investigated in vitro for their antiproliferative activity against HeLa (cervix epithelial adenocarcinoma), A431 (skin epidermoid carcinoma), A2780 (ovarian carcinoma), and MCF7 (breast epithelial adenocarcinoma) cells, using the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. A total of 68 n-hexane, chloroform, 50% methanol, and water extracts of selected species were screened for their potential cell growth inhibitory activity. Our experiments revealed that 7 of 17 species demonstrated notable antiproliferative activity (at least 50% inhibition of cell proliferation) against one or more cell lines. Kuehneromyces mutabilis, Lactarius quietus, and Lentinellus cochleatus, which exerted the highest activity on cancer cells, are considered valuable species in the perspective of further mycochemical studies. PMID- 26854102 TI - Simple and Reproducible Two-Stage Agitation Speed Control Strategy for Enhanced Triterpene Production by Lingzhi or Reishi Medicinal Mushrooms, Ganoderma lucidum ACCC G0119 (Higher Basidiomycetes) Based on Submerged Liquid Fermentation. AB - Triterpenes are important anticancer agents produced by batch submerged liquid fermentation, with the medicinal mushroom Ganoderma lucidum ACCC G0119, which was investigated under various dissolved oxygen levels by varying agitation speeds. Three kinetic parameters were analyzed: specific mycelial growth rate (MUsmg), specific glucose consumption rate (qsgc), and specific triterpene production rate (qstp). High concentration, yield, and productivity of triterpenes were achieved by developing a simple and reproducible two-stage agitation speed control strategy. At the first 40 h, agitation speed was controlled at 150 rpm to obtain the quickest peak qstp for triterpene production, subsequently agitation speed was controlled at 100 rpm to maintain high qstp for high triterpene accumulation. The maximum concentration of triterpenes reached 0.086 g/l with the yield of 6.072 g/kg and the productivity of 6.532 * 10-4 g/(l.h), which were 39.61%, 36.48%, and 49.22%, respectively, better than the best results controlled by fixed agitation speeds. Conceivably, such a triterpene fermentation production strategy would be useful for industrial large-scale production of triterpenes with G. lucidum. PMID- 26854103 TI - Contents and Antioxidant Activities of Polysaccharides in 14 Wild Mushroom Species from the Forest of Northeastern China. AB - This study aimed to evaluate the polysaccharide contents and antioxidant activities of 14 important wild mushroom species in the Lesser Khingan Range Forest of northeastern China. The fungal species were identified by morphology and DNA matching, belonging to six families: Polyporaceae (four species), Tricholomataceae (three), Russulaceae (three), Lepiotaceae (two), Lycoperdaceae (one), and Paxillaceae (one). Polysaccharides were isolated and partially purified from the water extract of each m ushroom by ethanol precipitation, deproteinization, and dialysis. Antioxidant activities of the mushroom polysaccharides were found to vary with both the species and the assay methods, and the highest three were from Handkea utriformis (535.8 MUmol trolox/g), Macrolepiota mastoidea (378.6), and Armillaria ostoyae (329.1) in radical scavenging; H. utriformis (5.94 mmol Fe/g), Lepista nuda (4.65), and A. ostoyae (4.42) in reducing power; and Armillariela cepistipes (484.6 MUmol Fe2+/g), H. utriformis (274.8), and M. mastoidea (202.5) in Fe2+ chelating. Several of the polysaccharides showed notable anti-tyrosinase activities, and that of Chroogomphus rutilus was the most potent with an IC50 of 0.46 mg/ml. These wild mushrooms can be useful sources of polysaccharides as potential antioxidants and tyrosinase inhibitors. This is the first systematic study on the wild mushroom species, as well as their polysaccharide contents and biological activities, from this forest. PMID- 26854104 TI - Antioxidant Potential of Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Higher Basidiomycetes) Cultivated on Artocarpus heterophyllus Sawdust Substrate in India. AB - The artificial cultivation of Ganoderma lucidum (MTCC1039) using Artocarpus heterophyllus as sawdust substrate was optimized and free radical scavenging activities of the generated fruiting bodies were investigated. The choice of A. heterophyllus as substrate was due to its easy availability in South India. Sawdust supplemented with dextrose medium yielded better spawn hyphae and early fruiting body initiation (15 days). The biological yield obtained was 42.06 +/- 2.14 g/packet and the biological efficiency was 8.41 +/- 0.48%. Both aqueous and methanolic extracts of fruiting body were analyzed for radical scavenging activity. Methanolic extract showed maximum scavenging activity for 1,1-diphenyl 2-picrylhydrazyl (IC50 = 290 MUg/ml) and 2,2'-azino-bis(3-ethylbenzothiazoline- 6 sulphonic acid (IC50 = 580 MUg/ml), whereas aqueous extract had better scavenging for ferric reducing antioxidant power (IC50 = 5 MUg/ml). Total phenolic content and total antioxidant capacity were significantly higher in methanolic extract (p < 0.01). A positive correlation existed between the phenolic content and antioxidant activity. Our results indicated that fruiting bodies of G. lucidum cultivated in sawdust medium possess antioxidant property, which can be exploited for therapeutic application. PMID- 26854105 TI - Chemical Composition and Antioxidant Activity of Two Wild Edible Mushrooms from Turkey. AB - The purpose of this study was to determine the antioxidant and antiradical activities in methanol extracts of two edible mushrooms from Turkey, Agaricus urinascens (Jul. Schaff. & F.H. Moller) Singer and Volvopluteus gloiocephala (DC.) Vizzini, Contu & Justo, as well as to examine trace elements (Cu, Zn, Fe, Mn, Co, Cr, Cd, Pb), minerals (Mg, Ca, K, Na) and vitamin C content. The levels of trace elements and minerals were determined by inductively coupled plasma atomic emission spectroscopy. Vitamin C and antioxidant properties were measured with a spectrophotometer. According to the results, total antioxidant activity and phenolic and flavonoid contents of A. urinascens and V. gloiocephala were 67.53 +/- 2.54 mM ascorbic acid/g and 31.68 +/- 2.27 mM ascorbic acid/g, 6.88 +/- 0.31 mg GA/g and 5.22 +/- 0.53 mg GA/g, and 3.80 +/- 0.04 mg QE/g and 2.60 +/- 0.20 mg QE/g, respectively. The findings of this study indicated that methanol extract of A. urinascens has a significant antioxidant activity and contents of total phenolic and flavonoid compounds. However, V. gloiocephala contains high levels of Ca, Cr, Fe, K, Mg, Mn, and Na, whereas A. urinascens contains higher levels of Cd, Co, Cu, Pb, and Zn than that of V. gloiocephala. Some trace elements that are in the compound of macrofungi may contribute the antioxidant capacity of macrofungi. A. urinascens has the ability to accumulate some heavy metals that prevent environmental metal pollution and can be used as a biomonitor. A. urinascens is expected to be used as an antioxidant in future studies of experimental animal models, against free radicals generated in response to oxidative stress. PMID- 26854106 TI - Immune-Modulating Activity of Extract Prepared from Mycelial Culture of Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes). AB - Ophiocordyceps sinensis is a natural fungus that has been valued as a health food and traditional Chinese medicine for centuries. The fungus is parasitic and colonizes insect larva. Naturally occurring O. sinensis thrives at high altitude in cold and grassy alpine meadows on the Himalayan mountain ranges. Wild O. sinensis is becoming increasingly rare in its natural habitats, and its price is out of reach for clinical practice. For these reasons, development of a standardized alternative is a great focus of research to allow the use of O. sinensis as a medicine. To develop an alternative for wild O. sinensis, a refined standardized extract, CBG-CS-2, was produced by artificial fermentation and extraction of the mycelial strain Paecilomyces hepiali CBG-CS-1, which originated from wild O. sinensis. In this study, we analyzed the in vivo immune-modulating effect of CBG-CS-2 in mice. Oral administration of CBG-CS-2 supported splenocyte stimulation and enhanced Th1-type cytokine expression from the splenocytes. Importantly, the same treatment significantly enhanced the natural killer cell activity of the splenocytes. Finally, oral administration of CBG-CS-2 enhanced the potential for inflammatory responses. Together, these findings indicate that the mycelial culture extract prepared from O. sinensis exhibited immune modulating activity and suggest its possible use in the treatment of diseases caused by abnormal immune function. PMID- 26854107 TI - From efficacy in trials to effectiveness in clinical practice: The Swedish Stroke Prevention Study. AB - Blood pressure treatment has shown great efficacy in reducing cardiovascular events in randomized controlled trials. If this is effective in reducing cardiovascular disease in the general population, is less studied. Between 2001 and 2009 we performed an intervention to improve blood pressure control in the county of Vasterbotten, using Sodermanland County as a control. The intervention was directed towards primary care physicians and included lectures on blood pressure treatment, a computerized decision support system with treatment recommendations, and yearly feed back on hypertension control. Each county had approximately 255 000 inhabitants. Differences in age and incidence of cardiovascular disease were small. During follow-up, more than 400 000 patients had their blood pressure recorded. The mean number of measurements was eight per patient, yielding a total of 3.4 million blood pressure recordings. The effect of the intervention will be estimated combining the blood pressure data collected from the electronic medical records, with data on stroke, myocardial infarction and mortality from Swedish health registers. Additional variables, from health registers and Statistics Sweden, will be collected to address for confounders. The blood pressure data collected within this study will be an important asset for future epidemiological studies within the field of hypertension. PMID- 26854108 TI - Development of a restriction length polymorphism combined with direct PCR technique to differentiate goose and Muscovy duck parvoviruses. AB - A restriction fragment length polymorphism combined with direct PCR technique to differentiate goose and Muscovy duck parvoviruses (GPV and MDPV) was developed based on comparison of the NS gene of GPV and MDPV. Both GPV and MDPV genomic DNA can be amplified with 641 bp using the specific PCR primers. The PCR fragments can be cut into 463 bp and 178 bp only in the case of MDPV-derived PCR products, whereas the GPV-derived PCR products cannot. The method established in this study can be used to differentiate GPV and MDPV with high specificity and precision, by using a direct PCR kit and QuickCut enzyme, as quickly as conventional PCR. PMID- 26854109 TI - Tensin2-deficient mice on FVB/N background develop severe glomerular disease. AB - Tensin2 (Tns2) is an essential component for the maintenance of glomerular basement membrane (GBM) structures. Tns2-deficient mice were previously shown to develop mild glomerular injury on a DBA/2 background, but not on a C57BL/6J or a 129/SvJ background, suggesting that glomerular injury by the deletion of Tns2 was strongly dependent on the genetic background. To further understand the mechanisms for the onset and the progression of glomerular injury by the deletion of Tns2, we generated Tns2-deficient mice on an FVB/N (FVB) strain, which is highly sensitive to glomerular disease. Tns2-deficient mice on FVB (FVBGN) developed severe nephrotic syndrome, and female FVBGN mice died within 8 weeks. Ultrastructural analysis revealed that FVBGN mice exhibited severe glomerular defects with mesangial process invasion of glomerular capillary tufts, lamination and thickening of the GBM and subsequent podocyte foot process effacement soon after birth. Aberrant laminin components containing alpha1, alpha2 and beta1 chains, which are normally expressed in the mesangium, accumulated in the GBM of FVBGN, suggesting that these components originated from mesangial cells that invaded glomerular capillary tufts. Compared to Tns2-deficient mice on the other backgrounds in previous reports, FVBGN mice developed earlier onset of glomerular defects and rapid progression of renal failure. Thus, this study further extended our understanding of the possible genetic background effect on the deterioration of nephrotic syndrome by Tns2 deficiency. PMID- 26854110 TI - Calcinated egg shell as a candidate of biosecurity enhancement material. AB - Calcinated egg shell (Egg-CaO), of which the main component is calcium oxide, was evaluated in the forms of powder and aqueous solutions for their efficacies as disinfectants against avian influenza virus (AIV), Newcastle disease virus (NDV), infectious bursal disease virus (IBDV), Salmonella Infantis and Escherichia coli. Egg-CaO powder inactivated these viruses within 3 min in the presence of 33% of fetal bovine serum (FBS). In Egg-CaO solutions, except AIV, all pathogens were inactivated within 1 hr, even in the presence of 5% of FBS. Without FBS, all pathogens, except AIV, were inactivated within 3 min, and AIV within 1 hr. In addition, persistence of virucidal activity against AIV and NDV of Egg-CaO powder was confirmed after exposure to sunlight for 2 weeks or resuspension with water for 7 times, simulating field harsh environments. Chick growth test was conducted to ensure the safety of the use of Egg-CaO powder in chicken cages and showed that it is safe to add Egg-CaO in litter or feed. In conclusion, Egg-CaO can be useful for the enhancement of biosecurity at farms. PMID- 26854111 TI - Reply to Dr. Kawada "Short sleep duration and serum copper". PMID- 26854112 TI - Transcriptional changes are involved in phenotype switching in Streptococcus equi subspecies equi. AB - Phenotypic heterogeneity within a population of bacteria, through genetic or transcriptional variation, enables survival and persistence in challenging and changing environments. We report here that a recent clinical isolate of S. equi, strain 1691 (Se1691), yielded a mixture of reduced capsule and mucoid colonies on primary isolation when grown on colistin-oxolinic acid blood agar (COBA) streptococcal selective plates. Passaging colonies of Se1691, with a reduced capsule phenotype maintained this mixed phenotype. In contrast, passaging mucoid colonies fixed the mucoid phenotype, suggesting adaptive genetic or transcriptional changes in response to growth on artificial media. However, despite obvious phenotypic and transcriptional differences, there were no apparent differences in the genome sequences of Se1691 recovered from colonies with a mucoid or reduced capsule phenotype. We identified 105 differentially transcribed genes in the transcriptomes of reduced capsule and mucoid colonies. The reduced capsule phenotype was associated with a significant reduction in transcription of the has locus (SEQ_0269 Q = 0.0015, SEQ_0270 Q = 0.0015, SEQ_0271 Q = 0.0285) and the amount of hyaluronic acid on the surface of S. equi recovered from non-mucoid colonies (P = 0.017). Significant differences in the transcription of 21 surface and secreted proteins were also observed. Our data show that changes in the bacterial transcriptome are linked to the mixed colony phenotype of Se1691. PMID- 26854113 TI - Context-Specific Associations Between Harsh Parenting and Peer Rejection on Child Conduct Problems at Home and School. AB - Although harsh parenting and peer rejection are independently associated with childhood conduct problems (CP), these patterns are often informant specific, suggesting that their associations across contexts (i.e., home and school) should be considered. In a sample of 142 children with and without attention deficit/hyperactivity disorder (ADHD; ages 5-10; 66% male), we used structural equation modeling to evaluate the structure of multi-informant (parent, teacher) and multimethod (semi-structured interview, questionnaire) rated aggressive, rule breaking, and oppositional behavior. Next, we explored context-specific associations by modeling harsh parenting and peer rejection as simultaneous and independent predictors of home and school CP. We observed several key findings: (a) the structure of parent- and teacher-reported CP was best accounted by context-specific CP (i.e., home vs. school) and a second-order general CP factor; (b) harsh punishment and peer rejection each independently predicted the second order general CP factor; and (c) peer rejection was uniquely associated with school CP, whereas harsh punishment was associated only with the second-order general CP factor and did not exhibit specificity with home CP. Whereas harsh parenting and peer rejection were each independently associated with generalized CP, peer rejection showed an additional, unique context-specific association with CP exclusively expressed at school. We discuss potential explanatory mechanisms underlying context-specific associations of CP, as well as address etiological and clinical implications for understanding informant-discrepancies in CP. PMID- 26854114 TI - Kinetic models - mathematical models of everything?: Comment on "Collective learning modeling based on the kinetic theory of active particles" by D. Burini et al. PMID- 26854115 TI - New therapies for chronic hepatitis B. AB - Approximately 350 million people worldwide are chronically infected with hepatitis B virus (HBV), representing a significant public health challenge. Nucleos/tide analogues (NUCs) and interferon alpha (IFNalpha), the current standard of care for chronic infection, aim at preventing progression of the disease to cirrhosis, hepatocellular carcinoma (HCC) and death. However, in contrast to the case of hepatitis C virus infection, in which novel antiviral drugs cure the vast majority of treated patients, in regard to HBV, cure is rare due to the unusual persistence of viral DNA in the form of covalently closed circular DNA (cccDNA) within the nucleus of infected cells. Available therapies for HBV require lifelong treatment and surveillance, as reactivation frequently occurs following medication cessation and the occurrence of HCC is decreased but not eliminated, even after years of successful viral suppression. Progress has been made in the development of new therapeutics, and it is likely that only a combination of immune modulators, inhibitors of gene expression and replication and cccDNA-targeting drugs will eradicate chronic infection. This review aims to summarize the state of the art in HBV drug research highlighting those agents with the greatest potential for success based on in vitro as well as on data from clinical studies. PMID- 26854116 TI - The application of knemometry to measure childhood short-term growth among the indigenous Shuar of Ecuador. AB - OBJECTIVES: Knemometry, the precise measurement of lower leg (LL) length, suggests that childhood short-term (e.g., weekly) growth is a dynamic, nonlinear process. However, owing to the large size and complexity of the traditional knemometer device, previous study of short-term growth among children has been restricted predominantly to clinical settings in industrialized Western nations. The aim of the present study is to address this limitation and promote broader understandings of global variation in childhood development by: (1) describing a custom-built portable knemometer and assessing its performance in the field; and (2) demonstrating the potential application of such a device by characterizing childhood short-term LL growth among the indigenous Shuar of Amazonian Ecuador. MATERIALS AND METHODS: Mixed-longitudinal LL length data were collected weekly from 336 Shuar children age 5-12 years old using the custom portable knemometer (n = 1,145 total observations). Device performance and Shuar short-term LL growth were explored using linear mixed effects models and descriptive statistics. RESULTS: The portable knemometer performed well across a range of participant characteristics and possesses a low technical error of measurement of 0.18 mm. Shuar childhood LL growth averages 0.47 mm/week (SD = 0.75 mm/week), but exhibits large between- and within-individual variation. DISCUSSION: Knemometry can be reliably performed in the field, providing a means for evaluating childhood short term growth among genetically and ecologically diverse populations. Preliminary findings suggest that Shuar weekly LL growth is comparable in mean magnitude but likely more variable than reported for healthy Western children. Future work will further explore these patterns. Am J Phys Anthropol 160:353-357, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26854118 TI - Aminophenol isomers unraveled by conformer-specific far-IR action spectroscopy. AB - Spectroscopic studies of molecular structure can strongly benefit from extending the conventional mid-IR range to the far-IR and THz regions, as low-frequency molecular vibrations provide unique fingerprints and high sensitivity to intra- and intermolecular interactions. In this work, the gas-phase conformer specific far-IR spectra of aminophenol isomers, recorded in the spectral range of 220-800 cm(-1) at the free-electron laser laboratory FELIX in Nijmegen (the Netherlands), are reported. Many distinct far-IR vibrational signatures which are specific for the molecular structure of the different aminophenol isomers are revealed and assigned. The observed far-IR transitions of the NH2 wagging (inversion) motion have been treated with a double-minimum harmonic well potential model that has enabled us to obtain the inversion barrier values. Moreover, we discuss the limitations and capability of conventional DFT frequency calculations to describe the far-IR vibrational modes. PMID- 26854119 TI - Identification of early vascular calcification with (18)F-sodium fluoride: potential clinical application. AB - Vascular calcification plays a prominent role in cardiovascular disease. Once considered to be a passive consequence of aging, this pathological process is now accepted to be dynamic and tightly regulated, its onset triggered by inflammation and necrosis and its progression bearing key similarities to osteogenesis. A major potential advance in our ability to understand the natural history and clinical implications of vascular calcification is the detection of its early and dynamic stages through the use of the positron-emitting radiotracer, (18)F-sodium fluoride. Alongside anatomical information gained from computed tomography, hybrid positron emission and computed tomography (PET/CT) imaging with (18)F sodium fluoride has, for the first time, enabled the non-invasive detection of microcalcification within the aortic valve, great vessels, and vulnerable coronary plaque. This has raised promise that exploring this process may allow improved risk prediction, better application of current therapies and ultimately the development of novel treatments to target this widespread pathology. PMID- 26854117 TI - Factors influencing Recombinase polymerase amplification (RPA) assay outcomes at point of care. AB - Recombinase Polymerase Amplification (RPA) can be used to detect pathogen specific DNA or RNA in under 20 min without the need for complex instrumentation. These properties enable its potential use in resource limited settings. However, there are concerns that deviations from the manufacturer's protocol and/or storage conditions could influence its performance in low resource settings. RPA amplification relies upon viscous crowding agents for optimal nucleic acid amplification, and thus an interval mixing step after 3-6 min of incubation is recommended to distribute amplicons and improve performance. In this study we used a HIV-1 RPA assay to evaluate the effects of this mixing step on assay performance. A lack of mixing led to a longer time to amplification and inferior detection signal, compromising the sensitivity of the assay. However lowering the assay volume from 50 MUL to 5 MUL showed similar sensitivity with or without mixing. We present the first peer-reviewed study that assesses long term stability of RPA reagents without a cold chain. Reagents stored at -20 degrees C, and 25 degrees C for up to 12 weeks were able to detect 10 HIV-1 DNA copies. Reagents stored at 45 degrees C for up to 3 weeks were able to detect 10 HIV-1 DNA copies, with reduced sensitivity only after >3 weeks at 45 degrees C. Together our results show that reducing reaction volumes bypassed the need for the mixing step and that RPA reagents were stable even when stored for 3 weeks at very high temperatures. PMID- 26854120 TI - First airborne pathogen direct analysis system. AB - We report a portable "sample to answer" system for the rapid detection of airborne pathogens for the first time. The system contains a key microfluidic chip which fulfills both pathogen enrichment and biological identification functions. The system realizes simple operation and less human intervention as well as minimum reagent contamination. The operation is user-friendly and suitable for field and point-of-care applications. The system is capable of handling detection of different pathogens by changing the primers. PMID- 26854121 TI - Physical exercise as a treatment for adult and juvenile myositis. AB - There is growing evidence to support the safety and efficacy of exercise in patients with adult and juvenile idiopathic inflammatory myopathies. Five randomized controlled trials including adult patients with polymyositis and dermatomyositis (DM) and additional open studies have demonstrated reduced impairment and activity limitation as well as improved quality of life. In addition, recent studies have shown reduced disease activity assessed by consensus disease activity measures and reduced expression of genes regulating inflammation and fibrosis. Furthermore, exercise could improve muscle aerobic capacity as shown by increased mitochondrial enzyme activity. These data suggest that intensive aerobic exercise and resistance training could reduce disease activity and inflammation and improve muscle metabolism. Encouraging results have been reported from available open studies including patients with inclusion body myositis (IBM) and juvenile DM, indicating reduced impairment, activity limitation and improved quality of life also in these patients. Larger studies are needed to increase understanding of the effects of exercise in patients with active, recent-onset polymyositis and DM as well as in patients with IBM and juvenile DM. PMID- 26854122 TI - Copper-mediated aerobic (phenylsulfonyl)difluoromethylation of arylboronic acids with difluoromethyl phenyl sulfone. AB - A new method for the generation of the "PhSO2CF2Cu" species from readily available difluoromethyl phenyl sulfone (PhSO2CF2H) has been developed. The "PhSO2CF2Cu" reagent can be applied in (phenylsulfonyl)difluoromethylation of arylboronic acids, which affords a convenient approach to introducing the PhSO2CF2 group into aromatics. PMID- 26854124 TI - Organic base-catalysed solvent-tuned chemoselective carbotrifluoromethylation and oxytrifluoromethylation of unactivated alkenes. AB - An unprecedented and efficient organic base-catalysed highly chemoselective carbo and oxytrifluoromethylation of unactivated alkenes with Togni's reagent was developed. The switchable chemoselectivity was tuned by simply changing the organic base catalyst and solvent. Mechanistic studies indicated that a radical cyclization pathway for carbotrifluoromethylation in DMSO and a carbocation pathway for oxytrifluoromethylation in DCE were probably involved. PMID- 26854123 TI - Sustained efficacy of insulin pump therapy compared with multiple daily injections in type 2 diabetes: 12-month data from the OpT2mise randomized trial. AB - AIMS: To compare insulin pump therapy and multiple daily injections (MDI) in patients with type 2 diabetes receiving basal and prandial insulin analogues. METHODS: After a 2-month dose-optimization period, 331 patients with glycated haemoglobin (HbA1c) levels >=8.0% and <=12% were randomized to pump therapy or continued MDI for 6 months [randomization phase (RP)]. The MDI group was subsequently switched to pump therapy during a 6-month continuation phase (CP). The primary endpoint was the between-group difference in change in mean HbA1c from baseline to the end of the RP. RESULTS: The mean HbA1c at baseline was 9% in both groups. At the end of the RP, the reduction in HbA1c was significantly greater with pump therapy than with MDI (-1.1 +/- 1.2% vs -0.4 +/- 1.1%; p < 0.001). The pump therapy group maintained this improvement to 12 months while the MDI group, which was switched to pump therapy, showed a 0.8% reduction: the final HbA1c level was identical in both arms. In the RP, total daily insulin dose (TDD) was 20.4% lower with pump therapy than with MDI and remained stable in the CP. The MDI-pump group showed a 19% decline in TDD, such that by 12 months TDD was equivalent in both groups. There were no differences in weight gain or ketoacidosis between groups. In the CP, one patient in each group experienced severe hypoglycaemia. CONCLUSIONS: Pump therapy has a sustained durable effect on glycaemic control in uncontrolled type 2 diabetes. PMID- 26854125 TI - Allosteric Modulation of Sigma-1 Receptors Elicits Rapid Antidepressant Activity. AB - AIMS: Sigma-1 receptors are involved in the pathophysiological process of several neuropsychiatric diseases such as epilepsy, depression. Allosteric modulation represents an important mechanism for receptor functional regulation. In this study, we examined antidepressant activity of the latest identified novel and selective allosteric modulator of sigma-1 receptor 3-methyl-phenyl-2, 3, 4, 5 tetrahydro-1H-benzo[d]azepin-7-ol (SOMCL-668). METHODS AND RESULTS: A single administration of SOMCL-668 decreased the immobility time in the forced swimming test (FST) and tailing suspended test in mice, which were abolished by pretreatment of sigma-1 receptor antagonist BD1047. In the chronic unpredicted mild stress (CUMS) model, chronic application of SOMCL-668 rapidly ameliorated anhedonia-like behavior (within a week), accompanying with the enhanced expression of brain-derived neurotrophic factor (BDNF) and phosphorylation of glycogen synthase kinase 3beta (GSK3beta) (Ser-9) in the hippocampus. SOMCL-668 also rapidly promoted the phosphorylation of GSK3beta (Ser-9) in an allosteric manner in vitro. In the cultured primary neurons, SOMCL-668 enhanced the sigma-1 receptor agonist-induced neurite outgrowth and the secretion of BDNF. CONCLUSION: SOMCL-668, a novel allosteric modulator of sigma-1 receptors, elicits a potent and rapid acting antidepressant effect. The present data provide the first evidence that allosteric modulation of sigma-1 receptors may represent a new approach for antidepressant drug discovery. PMID- 26854127 TI - Localization of histamine (H1, H2, H3 and H4) receptors in mouse inner ear. AB - Conclusion The present findings show that all four types of histamine receptors (H1R, H2R, H3R, and H4R) are present in the inner ear, thus supporting the hypothesis that histamine plays a physiological role in the inner ear. Objective To analyse the presence of histamine receptors in the normal mouse inner ear. Methods CBA/J mice were used in this study. The localization of H1R, H2R, H3R, and H4R in the inner ear, i.e. cochlea, vestibular end organs, vestibular ganglion, and endolymphatic sac, was studied by real-time PCR and immunohistochemistry. Results The mRNA for each receptor sub-type was detected in the inner ear. In the immunohistochemical study, the organ of Corti, spiral ganglion, vestibular ganglion, vestibular sensory epithelium, and endolymphatic sac cells showed an immunofluorescent reaction to all histamine receptors. PMID- 26854126 TI - Histidine biosynthesis plays a crucial role in metal homeostasis and virulence of Aspergillus fumigatus. AB - Aspergillus fumigatus is the most prevalent airborne fungal pathogen causing invasive fungal infections in immunosuppressed individuals. The histidine biosynthetic pathway is found in bacteria, archaebacteria, lower eukaryotes, and plants, but is absent in mammals. Here we demonstrate that deletion of the gene encoding imidazoleglycerol-phosphate dehydratase (HisB) in A. fumigatus causes (i) histidine auxotrophy, (ii) decreased resistance to both starvation and excess of various heavy metals, including iron, copper and zinc, which play a pivotal role in antimicrobial host defense, (iii) attenuation of pathogenicity in 4 virulence models: murine pulmonary infection, murine systemic infection, murine corneal infection, and wax moth larvae. In agreement with the in vivo importance of histidine biosynthesis, the HisB inhibitor 3-amino-1,2,4-triazole reduced the virulence of the A. fumigatus wild type and histidine supplementation partially rescued virulence of the histidine-auxotrophic mutant in the wax moth model. Taken together, this study reveals limited histidine availability in diverse A. fumigatus host niches, a crucial role for histidine in metal homeostasis, and the histidine biosynthetic pathway as being an attractive target for development of novel antifungal therapy approaches. PMID- 26854128 TI - Headache Doctors in London's Green Park. PMID- 26854130 TI - Elucidation of hypoglycemic action and toxicity studies of insulin-like protein from Costus igneus. AB - We have reported earlier, an orally active insulin-like protein (ILP) from Costus igneus having potent hypoglycemic property in STZ-induced diabetic Swiss mice. The blood glucose level was reduced significantly within two hours after feeding ILP orally in an oral glucose tolerance test. The present study elucidates the mechanism underlying the hypoglycemic action of ILP. Mechanism of action of ILP was studied in differentiated L6 myotubes. 2-NBDG uptake stimulated by ILP was studied in differentiated L6 myotubes under normoglycemic, hyperglycemic and induced insulin resistant conditions. ILP treatment significantly increased 2 NBDG uptake in differentiated L6 myotubes. The levels of insulin signaling molecules IRS-1 and GLUT-4 were assessed in ILP treated L6 myotubes by immunoblot analysis of cytoplasmic and plasma membrane fractions respectively. Immunoblot analysis revealed an increase in cytoplasmic IRS-1 with a concomitant increase in GLUT-4 translocation to the plasma membrane in a time dependent manner. Toxicity studies of ILP were performed on normal as well as diabetic Swiss albino mice. ILP did not show any toxicity in the acute and sub-chronic toxicity studies in normal as well as diabetic Swiss albino mice. Mass spectrometry was carried out to identify ILP. MALDI TOF/TOF MS analysis of ILP revealed sequence homology with the predicted protein from Physcomitrella patens. Our study reveals that ILP acts via insulin signaling pathway and can be used as oral insulin mimetic. PMID- 26854129 TI - Common and rare CARD14 gene variants affect the antitumour necrosis factor response among patients with psoriasis. AB - BACKGROUND: The CARD14 gene encodes a protein that enhances nuclear factor (NF) kappaB activation and the upregulation of proinflammatory pathway genes. CARD14 is upregulated in psoriatic vs. normal skin, and rare and common CARD14 variants have been associated with the risk of developing psoriasis. Our hypothesis was that CARD14 variants could also influence the response to antitumour necrosis factor (anti-TNF) therapies among patients with psoriasis. OBJECTIVES: To determine whether CARD14 gene variants were linked to a significant positive anti TNF response in patients with psoriasis. METHODS: DNA from 116 patients with psoriasis was subjected to next-generation sequencing of the CARD14 gene. All of the patients were nonresponders or had contraindications to conventional systemic treatments. RESULTS: A reduction of at least 75% in Psoriasis Area and Severity Index (PASI 75) at week 24 was considered a positive response to treatment. In total 116 patients (79 responders and 37 nonresponders) were next-generation sequenced, and we identified five nucleotide variants that would result in missense amino acid changes. These variants were determined in all of the patients, and allele and genotype frequencies were compared between the two groups. We found a significantly higher frequency of rs11652075 CC (p.Arg820Trp) among the group with a positive response (P = 0.01, odds ratio 3.71, 95% confidence interval 1.30-10.51). Furthermore, among responders, six patients were heterozygous carriers of the rare p.Glu422Lys variant, and two patients were heterozygous for p.Arg682Trp (P = 0.04). CONCLUSIONS: The common CARD14 p.Arg820Trp variant might have a significant effect on the response to anti-TNF therapies among patients with psoriasis. In addition, rare CARD14 missense variants could also predispose to a better response. PMID- 26854132 TI - Sleep problems and internet addiction among children and adolescents: a longitudinal study. AB - Although the literature has documented associations between sleep problems and internet addiction, the temporal direction of these relationships has not been established. The purpose of this study is to evaluate the bidirectional relationships between sleep problems and internet addiction among children and adolescents longitudinally. A four-wave longitudinal study was conducted with 1253 children and adolescents in grades 3, 5 and 8 from March 2013 to January 2014. The sleep problems of the student participants were measured by parental reports on the Sleep Habit Questionnaire, which catalogues early insomnia, middle insomnia, disturbed circadian rhythm, periodic leg movements, sleep terrors, sleepwalking, sleep talking, nightmares, bruxism, snoring and sleep apnoea. The severity of internet addiction was measured by students' self-reports on the Chen Internet Addiction Scale. Based on the results of time-lag models, dyssomnias (odds ratio = 1.31), especially early and middle insomnias (odds ratio = 1.74 and 2.24), sequentially predicted internet addiction, and internet addiction sequentially predicted disturbed circadian rhythm (odds ratio = 2.40), regardless of adjustment for gender and age. This is the first study to demonstrate the temporal relationship of early and middle insomnia predicting internet addiction, which subsequently predicts disturbed circadian rhythm. These findings imply that treatment strategies for sleep problems and internet addiction should vary according to the order of their occurrence. PMID- 26854131 TI - Cyclofarnesoids and methylhexanoids produced from beta-carotene in Phycomyces blakesleeanus. AB - The oxidative cleavage of beta-carotene in the Mucorales produces three fragments of 18, 15, and 7 carbons, respective heads of three families of apocarotenoids: the methylhexanoids, the trisporoids, and the cyclofarnesoids (named after their 1,6-cyclofarnesane skeleton). The apocarotenoids are easily recognized because they are absent in white mutants unable to produce beta-carotene. In cultures of Phycomyces blakesleeanus we detected thirty-two apocarotenoids by LC, UV absorbance, and MS. With additional IR and NMR we identified two methylhexanoids and the eight most abundant cyclofarnesoids. Four of them were previously-unknown natural compounds, including 4-dihydrocyclofarnesine S, the most abundant cyclofarnesoid in young cultures. We arranged the apocarotenoids of the Mucorales in a scheme that helps classifying and naming them and suggests possible metabolites and biosynthetic pathways. We propose specific biosynthetic pathways for cyclofarnesoids and methylhexanoids based on structural comparisons, the time course of appearance of individual compounds, and the bioconversion of beta-apo 12-carotenol, an early precursor, to three more oxygenated cyclofarnesoids by the white mutants. Some of the reactions occur spontaneously in the increasingly acidic culture media. Mating increased the contents of methylhexanoids and cyclofarnesoids by ca. threefold in young cultures and ca. twelvefold in old ones (five days); cyclofarnesine S, the most abundant cyclofarnesoid in old cultures, increased over one hundredfold. We found no differences between the sexes and no activity as sexual pheromones, but we suggest that methylhexanoids and cyclofarnesoids could mediate species-specific physiology and behavior. PMID- 26854133 TI - Brain zinc chelation by diethyldithiocarbamate increased the behavioral and mitochondrial damages in zebrafish subjected to hypoxia. AB - The increase in brain levels of chelatable zinc (Zn) in dysfunctions involving oxygen deprivation has stimulated the treatment with Zn chelators, such as diethyldithiocarbamate (DEDTC). However, DEDTC is a redox-active compound and it should be better evaluated during hypoxia. We use the hypoxia model in zebrafish to evaluate DEDTC effects. The exploratory behavior, chelatable Zn content, activities of mitochondrial dehydrogenases, reactive species levels (nitric oxide, superoxide anion, hydroxyl radical scavenger capacity) and cellular antioxidants (sulfhydryl, superoxide dismutase) of zebrafish brain were assessed after recovery, with or without 0.2 mM DEDTC. The increased brain levels of chelatable Zn induced by hypoxia were mitigated by DEDTC. However, the novel tank task indicated that DEDTC did further enhance the exploratory deficit caused by hypoxia. Furthermore, these behavioral impairments caused by DEDTC were more associated with a negative action on mitochondrial activity and brain oxidative balance. Thus, due to apparent pro-oxidant action of DEDTC, our data do not support its use for neuroprotection in neuropathologies involving oxygen deprivation. PMID- 26854134 TI - Enhanced crude oil biodegradation in soil via biostimulation. AB - Research on feasible methods for the enhancement of bioremediation in soil contaminated by crude oil is vital in oil-exporting countries such as Kuwait, where crude oil is a major pollutant and the environment is hostile to biodegradation. This study investigated the possibility of enhancing crude oil bioremediation by supplementing soil with cost-effective organic materials derived from two widespread locally grown trees, Conocarpus and Tamarix. Amendments in soils increased the counts of soil microbiota by up to 98% and enhanced their activity by up to 95.5%. The increase in the biodegradation of crude oil (75%) and high levels of alkB expression substantiated the efficiency of the proposed amendment technology for the bioremediation of hydrocarbon contaminated sites. The identification of crude-oil-degrading bacteria revealed the dominance of the genus Microbacterium (39.6%), Sphingopyxis soli (19.3%), and Bordetella petrii (19.6%) in unamended, Conocarpus-amended, and Tamarix-amended contaminated soils, respectively. Although soil amendments favored the growth of Gram-negative bacteria and reduced bacterial diversity, the structures of bacterial communities were not significantly altered. PMID- 26854135 TI - Focal release of neurotrophic factors by biodegradable microspheres enhance motor and sensory axonal regeneration in vitro and in vivo. AB - Neurotrophic factors (NTFs) promote nerve regeneration and neuronal survival after peripheral nerve injury. However, drawbacks related with administration and bioactivity during long periods limit their therapeutic application. In this study, PLGA microspheres (MPs) were used to locally release different NTFs and evaluate whether they accelerate axonal regeneration in comparison with free NTFs or controls. ELISA, SEM, UV/visible light microscopy, organotypic cultures of DRG explants and spinal cord slices were used to characterize MP properties and the bioactivity of the released NTFs. Results of organotypic cultures showed that encapsulated NTFs maintain longer bioactivity and enhance neurite regeneration of both sensory and motor neurons compared with free NTFs. For in vivo assays, the rat sciatic nerve was transected and repaired with a silicone tube filled with collagen gel or collagen mixed with PBS encapsulated MPs (control groups) and with free or encapsulated NGF, BDNF, GDNF or FGF-2. After 20 days, a retrotracer was applied to the regenerated nerve to quantify motor and sensory axonal regeneration. NTF encapsulation in MPs improved regeneration of both motor and sensory axons, as evidenced by increased numbers of retrolabeled neurons. Hence, our results show that slow release of NTFs with PLGA MP enhance nerve regeneration. PMID- 26854136 TI - Exposure of isoflurane-treated cells to hyperoxia decreases cell viability and activates the mitochondrial apoptotic pathway. AB - Isoflurane has either neuroprotective or neurotoxic effects. High-dose oxygen is frequently used throughout the perioperative period. We hypothesized that hyperoxia will affect cell viability of rat pheochromocytoma (PC12) cells that were exposed to isoflurane and reactive oxygen species (ROS) may be involved. PC12 cells were exposed to 1.2% or 2.4% isoflurane for 6 or 24h respectively, and cell viability was evaluated. To investigate the effects of hyperoxia, PC12 cells were treated with 21%, 50%, or 95% oxygen and 2.4% isoflurane for 6h, and cell viability, TUNEL staining, ROS production, and expression of B-cell lymphoma 2 (BCL-2), BCL2-associated X protein (BAX), caspase-3 and beta-site APP cleaving enzyme (BACE) were measured. ROS involvement was evaluated using the ROS scavenger 2-mercaptopropiopylglycine (MPG). The viability of cells exposed to 2.4% isoflurane was lower than that of cells exposed to 1.2% isoflurane. Prolonged exposure (6h vs. 24h) to 2.4% isoflurane resulted in a profound reduction in cell viability. Treatment with 95% (but not 50%) oxygen enhanced the decrease in cell viability induced by 2.4% isoflurane alone. Levels of ROS, Bax, caspase-3 and BACE were increased, whereas expression of Bcl-2 was decreased, in cells treated with 95% oxygen plus 2.4% isoflurane compared with the control and 2.4% isoflurane plus air groups. MPG attenuated the effects of oxygen and isoflurane. In conclusion, isoflurane affects cell viability in a dose- and time dependent manner. This effect is augmented by hyperoxia and may involve ROS, the mitochondrial apoptotic signaling pathway, and beta-amyloid protein. PMID- 26854138 TI - Guanfacine promotes neuronal survival in medial prefrontal cortex under hypobaric hypoxia. AB - High altitude hypobaric hypoxia (HH) affects prefrontal cognitive and executive functions. Guanfacine, alpha 2A adrenoceptor agonist ameliorates the neurological outcomes of high altitude exposure and associated prefrontal neurodegeneration. However, the molecular mechanism underlying the neuroprotective effect of guanfacine following HH remains elusive. Altered balance of pro and anti apoptotic proteins have been implicated in the beneficial effect of guanfacine to enhance neuronal survival. We examined the effects of guanfacine on expression of some key neurotropic and cytoskeletal proteins following HH. Male rats were exposed to simulated altitude of 7620 m and received an intramuscular injection of either saline or guanfacine at a dose of 1mg/kg for 7 consecutive days. Differential expression of desired proteins was evaluated in layer II of medial prefrontal cortex (PFC) by biochemical and immunohistochemical assays. Guanfacine treatment significantly increased the expression of BDNF in layer II of the medial PFC during normoxia and HH. Moreover, there was a negative correlation of this neurotropic factor with neurodegeneration of pyramidal cells present in this layer of medial PFC. We found a significant decrease in Caspase3 and Bax while a significant increase in Bcl2 with guanfacine treatment during HH. Further, change in Bax to Bcl2 ratio was in correlation with Caspase3 expression in layer II of the medial PFC, indicating that Caspase3 is responsible for Bcl2 cleavage and hence modulation of apoptosis. Guanfacine treatment induced a marked and significant increase in MAP2 and Spinophilin expression in dendritic arbors and spines respectively. Interestingly, alteration in these cytoskeletal proteins was accompanied by simultaneous changes in morphological parameters of dendrites in layer II of medial PFC. Guanfacine modulates the neurotropic, cytoskeletal, pro and anti-apoptotic protein expression in medial PFC under HH and therefore serve as a countermeasure in the amelioration of HH induced alteration in these proteins. PMID- 26854137 TI - Modeling autism spectrum disorders with human neurons. AB - Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impaired social communication and interactions and by restricted and repetitive behaviors. Although ASD is suspected to have a heritable or sporadic genetic basis, its underlying etiology and pathogenesis are not well understood. Therefore, viable human neurons and glial cells produced using induced pluripotent stem cells (iPSC) to reprogram cells from individuals affected with ASD provide an unprecedented opportunity to elucidate the pathophysiology of these disorders, providing novel insights regarding ASD and a potential platform to develop and test therapeutic compounds. Herein, we discuss the state of art with regards to ASD modeling, including limitations of this technology, as well as potential future directions. This article is part of a Special Issue entitled SI: Exploiting human neurons. PMID- 26854139 TI - Relationship Between Mean Leucocyte Telomere Length and Measures of Allostatic Load in US Reproductive-Aged Women, NHANES 1999-2002. AB - BACKGROUND: Reproductive health disparities may be partly explained by the cumulative effects of chronic stress experienced by socially disadvantaged groups. Although, telomere length (TL) and allostatic load score have each been used as biological markers of stress, the relationship between these two measures is unknown. METHODS: We investigated the association between leucocyte TL and allostatic load score in 1503 non-pregnant women (20-44 years) participating in the National Health and Nutrition Examination Survey, 1999-2002. We constructed six different allostatic load scores using either quartile- or clinical-based cut points for 14 biomarkers based on previously published methods. We estimated associations between TL and allostatic load scores and component biomarkers using linear regression, also assessing interactions by race/ethnicity. RESULTS: After adjustment for age, longer TL was associated with higher HDL cholesterol and lower C-reactive protein and creatinine clearance; TL was not associated with the other component biomarkers. Shorter TL was associated with higher allostatic load scores for the two clinical cut-point-based scores after adjustment for age, but not the four scores based on quartile cut-points. Significant interactions by race/ethnicity were observed for TL and HbA1c and triglycerides, but not for other component biomarkers or allostatic load scores. CONCLUSIONS: Although TL and allostatic load score are both considered measures of cumulative stress, most component biomarkers and scores using quartile-based cut-points were not associated with TL. In reproductive-aged women, allostatic load scores using clinical-based cut-points were more strongly associated with TL compared with quartile-based scores. PMID- 26854140 TI - Evaluation of the Diagnostic Accuracy of Serum D-Dimer Levels in Pregnant Women with Adnexal Torsion. AB - We aimed to evaluate the diagnostic accuracy of serum D-dimer levels in pregnant women with adnexal torsion (AT). The pregnant women with ovarian cysts who suffered from pelvic pain were divided into two groups; the first group consisted of the cases with surgically proven as AT (n = 17) and the second group consisted of the cases whose pain were resolved in the course of follow-up period without required surgery (n = 34). The clinical characteristics and serum D-dimer levels were compared between the groups. Patients with AT had a higher rate of elevated serum white blood cell (WBC) count (57% vs. 16%, p = 0.04) and serum D-dimer levels (77% vs. 21%, p < 0.01) on admission in the study group than in the control group. Elevated D-dimer and cyst diameter larger than 5 cm yielded highest sensitivity (82% for each); whereas the presence of nausea and vomiting and elevated CRP had the highest specificity (85% and 88%, respectively). This is the first study that evaluates the serum D-dimer levels in humans in the diagnosis of AT, and our findings supported the use of D-dimer for the early diagnosis of AT in pregnant women. PMID- 26854141 TI - Mini-P-gp and P-gp Co-Expression in Brown Trout Erythrocytes: A Prospective Blood Biomarker of Aquatic Pollution. AB - In aquatic organisms, such as fish, blood is continually exposed to aquatic contaminants. Multidrug Resistance (MDR) proteins are ubiquitous detoxification membrane pumps, which recognize various xenobiotics. Moreover, their expression is induced by a large class of drugs and pollutants. We have highlighted the co expression of a mini P-gp of 75 kDa and a P-gp of 140 kDa in the primary culture of brown trout erythrocytes and in the erythrocytes of wild brown trout collected from three rivers in the Auvergne region of France. In vitro experiments showed that benzo[a]pyrene, a highly toxic pollutant model, induced the co-expression of mini-P-gp and P-gp in trout erythrocytes in a dose-dependent manner and relay type response. Similarly, in the erythrocytes of wild brown trout collected from rivers contaminated by a mixture of PAH and other multi-residues of pesticides, mini-P-gp and P-gp were able to modulate their expression, according to the nature of the pollutants. The differential and complementary responses of mini-P gp and P-gp in trout erythrocytes suggest the existence in blood cells of a real protective network against xenobiotics/drugs. This property could be exploited to develop a blood biomarker of river pollution. PMID- 26854142 TI - Technologies for Clinical Diagnosis Using Expired Human Breath Analysis. AB - This review elucidates the technologies in the field of exhaled breath analysis. Exhaled breath gas analysis offers an inexpensive, noninvasive and rapid method for detecting a large number of compounds under various conditions for health and disease states. There are various techniques to analyze some exhaled breath gases, including spectrometry, gas chromatography and spectroscopy. This review places emphasis on some of the critical biomarkers present in exhaled human breath, and its related effects. Additionally, various medical monitoring techniques used for breath analysis have been discussed. It also includes the current scenario of breath analysis with nanotechnology-oriented techniques. PMID- 26854143 TI - Positron Emission Tomography in Breast Cancer. AB - Gradually, FDG-PET/CT has been strengthening within the diagnostic algorithms of oncological diseases. In many of these, PET/CT has shown to be useful at different stages of the disease: diagnosis, staging or re-staging, treatment response assessment, and recurrence. Some of the advantages of this imaging modality versus CT, MRI, bone scan, mammography, or ultrasound, are based on its great diagnostic capacity since, according to the radiopharmaceutical used, it reflects metabolic changes that often occur before morphological changes and therefore allows us to stage at diagnosis. Moreover, another advantage of this technique is that it allows us to evaluate the whole body so it can be very useful for the detection of distant disease. With regard to breast cancer, FDG PET/CT has proven to be important when recurrence is suspected or in the evaluation of treatment response. The technological advancement of PET equipment through the development of new detectors and equipment designed specifically for breast imaging, and the development of more specific radiopharmaceuticals for the study of the different biological processes of breast cancer, will allow progress not only in making the diagnosis of the disease at an early stage but also in enabling personalized therapy for patients with breast cancer. PMID- 26854144 TI - Pain in the Blood? Envisioning Mechanism-Based Diagnoses and Biomarkers in Clinical Pain Medicine. AB - Chronic pain is highly prevalent, and pain medicine lacks objective biomarkers to guide diagnosis and choice of treatment. The current U.S. "opioid epidemic" is a reminder of the paucity of effective and safe treatment options. Traditional pain diagnoses according to the International Classification of Diseases are often unspecific, and analgesics are often prescribed on a trial-and-error basis. In contrast to this current state of affairs, the vision of future mechanism-based diagnoses of chronic pain conditions is presented in this non-technical paper, focusing on the need for biomarkers and the theoretical complexity of the task. Pain is and will remain a subjective experience, and as such is not objectively measurable. Therefore, the concept of "noci-marker" is presented as an alternative to "pain biomarker", the goal being to find objective, measurable correlates of the pathophysiological processes involved in different chronic pain conditions. This vision entails a call for more translational pain research in order to bridge the gap between clinical pain medicine and preclinical science. PMID- 26854146 TI - A Diagnostic Model for Dementia in Clinical Practice-Case Methodology Assisting Dementia Diagnosis. AB - Dementia diagnosis is important for many different reasons. Firstly, to separate dementia, or major neurocognitive disorder, from MCI (mild cognitive impairment), mild neurocognitive disorder. Secondly, to define the specific underlying brain disorder to aid treatment, prognosis and decisions regarding care needs and assistance. The diagnostic method of dementias is a puzzle of different data pieces to be fitted together in the best possible way to reach a clinical diagnosis. Using a modified case methodology concept, risk factors affecting cognitive reserve and symptoms constituting the basis of the brain damage hypothesis, can be visualized, balanced and reflected against test results as well as structural and biochemical markers. The model's origin is the case method initially described in Harvard business school, here modified to serve dementia diagnostics. PMID- 26854145 TI - Pharmacokinetic Analysis of (64)Cu-ATSM Dynamic PET in Human Xenograft Tumors in Mice. AB - The aim of this study was to evaluate the feasibility to perform voxel-wise kinetic modeling on datasets obtained from tumor-bearing mice that underwent dynamic PET scans with (64)Cu-ATSM and extract useful physiological parameters. METHODS: Tumor-bearing mice underwent 90-min dynamic PET scans with (64)Cu-ATSM and CT scans with contrast. Irreversible and reversible two-tissue compartment models were fitted to time activity curves (TACs) obtained from whole tumor volumes and compared using the Akaike information criterion (AIC). Based on voxel wise pharmacokinetic analysis, parametric maps of model rate constants k1, k3 and Ki were generated and compared to (64)Cu-ATSM uptake. RESULTS: Based on the AIC, an irreversible two-tissue compartment model was selected for voxel-wise pharmacokinetic analysis. Of the extracted parameters, k1 (~perfusion) showed a strong correlation with early tracer uptake (mean spearman R = 0.88) 5 min post injection (pi). Moreover, positive relationships were found between late tracer uptake (90 min pi) and both k3 and the net influx rate constant, Ki (mean spearman R = 0.56 and R = 0.86; respectively). CONCLUSION: This study shows the feasibility to extract relevant parameters from voxel-wise pharmacokinetic analysis to be used for preclinical validation of (64)Cu-ATSM as a hypoxia specific PET tracer. PMID- 26854148 TI - A Novel Point-of-Care Biomarker Recognition Method: Validation by Detecting Marker for Diabetic Nephropathy. AB - Biological fluid collection to identify and analyze different disease markers is a routine and normal procedure in health care settings. Body fluids are as varied as urine, blood, mucus, cerebrospinal fluid (CSF), tears, semen, etc. The volumes of the collected fluids range from micro liters (e.g., tears, CSF) to tens and hundreds of milliliters (blood, urine, etc.). In some manifestations, a disease marker (particularly protein markers) can occur in trace amounts, yet the fluids collected are in large volumes. To identify these trace markers, cumbersome methods, expensive instruments, and trained personnel are required. We developed an easy method to rapidly capture, concentrate, and identify protein markers in large volumes of test fluids. This method involves the utilization of two antibodies recognizing two different epitopes of the protein biomarker. Antibody 1 helps to capture and concentrate the biomarker and Antibody-2 adsorbed or conjugated to nanogold beads will detect the biomarker. This method was validated in capturing and detecting lipocalin type prostaglandin-D2 synthase, a marker in urine that implicates diabetic nephropathy. A one-step collection, concentration, and detection device was designed based on this method. This device can replace many of the normal body fluid collection devices such as tubes and containers. A one-step fluid collection and biomarker capture and concentration device for rapid diagnosis of diseases has tremendous advantage in terms of cost and providing timely results. PMID- 26854149 TI - Diagnostics for Developing Countries. AB - Improving the availability of high quality diagnostic tests for infectious diseases is a global priority. Lack of access by people living in low income countries may deprive them of life saving treatment and reduces opportunities to prevent onward transmission and spread of the disease. Diagnostic laboratories are often poorly resourced in developing countries, and sparsely distributed. Improved access may be achieved by using tests that do not require laboratory support, including rapid tests for use at the point-of-care. Despite increased interest, few new in vitro diagnostic (IVD) products reach the majority populations in low income countries. Barriers to uptake include cost and lack of robustness, with reduced test performances due to environmental pressures such as high ambient temperatures or dust. In addition to environmental factors test developers must consider the local epidemiology. Confounding conditions such as immunosuppression or variations in antigen presentation or genotype can affect test performance. Barriers to product development include access to finance to establish manufacturing capacity and cover the costs of market entry for new devices. Costs and delays may be inflated by current regulatory preregistration processes to ensure product safety and quality, and more harmonized approaches are needed. PMID- 26854150 TI - Quantitative Assessment of Tissue Perfusion in Hepatocellular Carcinoma Using Perflubutane Dynamic Contrast-Enhanced Ultrasonography: A Preliminary Study. AB - Our purpose in this study was to assess the relationship between contrast signal intensity (CI) and concentration of perflubutane microbubbles in a phantom experiment, and to examine the feasibility of this technique for quantitative analysis of vascularity in hepatocellular carcinoma (HCC). Microbubble solutions of the perflubutane contrast agent were prepared by mixing with purified water. We examined the relationship between CI in dB units and the concentration. Moreover, seven HCC patients were examined using real-time dynamic contrast imaging. The perfusion index was calculated from time-intensity curves generated for both HCC and surrounding liver parenchyma. We observed a linear relationship between the CIdB and the concentration in the phantom study and a higher perfusion index in the HCC lesions relative to the surrounding liver parenchyma. Dynamic contrast-enhanced ultrasonography with perflubutane microbubbles, which exhibit linear and temporally stable characteristics under continuous ultrasound exposure, allows the collection of quantitative hemodynamic information regarding HCC. PMID- 26854152 TI - Adrenal Vein Sampling for Conn's Syndrome: Diagnosis and Clinical Outcomes. AB - Adrenal vein sampling (AVS) is the gold standard test to determine unilateral causes of primary aldosteronism (PA). We have retrospectively characterized our experience with AVS including concordance of AVS results and imaging, and describe the approach for the PA patient in whom bilateral AVS is unsuccessful. We reviewed the medical records of 85 patients with PA and compared patients who were treated medically and surgically on pre-procedure presentation and post treatment outcomes, and evaluated how technically unsuccessful AVS results were used in further patient management. Out of the 92 AVS performed in 85 patients, AVS was technically successful bilaterally in 58 (63%) of cases. Either unsuccessful AVS prompted a repeat AVS, or results from the contralateral side and from CT imaging were used to guide further therapy. Patients who were managed surgically with adrenalectomy had higher initial blood pressure and lower potassium levels compared with patients who were managed medically. Adrenalectomy results in significantly decreased blood pressure and normalization of potassium levels. AVS can identify surgically curable causes of PA, but can be technically challenging. When one adrenal vein fails to be cannulated, results from the contralateral vein can be useful in conjunction with imaging and clinical findings to suggest further management. PMID- 26854153 TI - Unintended Consequences of not Specifying Exclusionary Illnesses for Systemic Exertion Intolerance Disease. AB - The Institute of Medicine recently proposed a new case definition for chronic fatigue syndrome (CFS), as well as a new name, Systemic Exertion Intolerance Disease (SEID). Contrary to the Fukuda et al.'s CFS case definition, there are few exclusionary illnesses specified for this new SEID case definition. The current study explored this decision regarding exclusionary illnesses using the SEID criteria with four distinct data sets involving patients who had been identified as having CFS, as well as healthy controls, community controls, and other illness groups. The findings indicate that many individuals from major depressive disorder illness groups as well as other medical illnesses were categorized as having SEID. The past CFS Fukuda et al. prevalence rate in a community based sample of 0.42 increased by 2.8 times with the new SEID criteria. The consequences for this broadening of the case definition are discussed. PMID- 26854147 TI - Neuroendocrine Carcinomas of the Gastroenteropancreatic System: A Comprehensive Review. AB - To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type. Concentrating on GEP-NECs, we can conclude that survival times are poor, with a median of only 4-16 months depending on disease stage and primary site. Further, this aggressive disease appears to be on the rise, with incidence numbers increasing while survival times are stagnant. Treatment strategies concerning surgery are often undecided and second-line chemotherapy is not yet established. After an analysis of over 2600 articles, we can conclude that there is indeed more empirical literature concerning GEP-NECs available than previously assumed. This unique review is based on 333 selected articles and contains detailed information concerning all aspects of GEP-NECs. Namely, the classification, histology, genetic abnormalities, epidemiology, origin, biochemistry, imaging, treatment and survival of GEP-NECs are described. Also, organ-specific summaries with more detail in relation to disease presentation, diagnosis, treatment and survival are presented. Finally, key points are discussed with directions for future research priorities. PMID- 26854154 TI - In Vivo Phenotyping of Tumor Metabolism in a Canine Cancer Patient with Simultaneous (18)F-FDG-PET and Hyperpolarized (13)C-Pyruvate Magnetic Resonance Spectroscopic Imaging (hyperPET): Mismatch Demonstrates that FDG may not Always Reflect the Warburg Effect. AB - In this communication the mismatch between simultaneous (18)F-FDG-PET and a (13)C lactate imaging (hyperPET) in a biopsy verified squamous cell carcinoma in the right tonsil of a canine cancer patient is shown. The results demonstrate that (18)F-FDG-PET may not always reflect the Warburg effect in all tumors. PMID- 26854155 TI - Brown Tumors Due to Primary Hyperparathyroidism in a Patient with Parathyroid Carcinoma Mimicking Skeletal Metastases on (18)F-FDG PET/CT. AB - Parathyroid carcinoma only represents <1% of all cases of primary hyperparathyroidism (PHPT). Even rare, chronic PHPT may lead to excessive osteoclast activity, and the increased resorption leads to destruction of cortical bone and formation of fibrous cysts with deposits of hemosiderin-so called brown tumors. These benign, osteolytic lesions may demonstrate FDG-avidity on (18)F-FDG PET/CT, and as such are misinterpreted as skeletal metastases. Regression of the lesions may occur following successful treatment. We present a case demonstrating the diagnostic work-up and follow-up of a patient with PHPT due to parathyroid carcinoma and with presence of brown tumors on (18)F-FDG PET/CT, visualizing the possible role of this imaging modality in the evaluation of treatment response in these patients. PMID- 26854156 TI - Hybrid Imaging for Patient-Specific Dosimetry in Radionuclide Therapy. AB - Radionuclide therapy aims to treat malignant diseases by systemic administration of radiopharmaceuticals, often using carrier molecules such as peptides and antibodies. The radionuclides used emit electrons or alpha particles as a consequence of radioactive decay, thus leading to local energy deposition. Administration to individual patients can be tailored with regards to the risk of toxicity in normal organs by using absorbed dose planning. The scintillation camera, employed in planar imaging or single-photon emission computed tomography (SPECT), generates images of the spatially and temporally varying activity distribution. Recent commercially available combined SPECT and computed tomography (CT) systems have dramatically increased the possibility of performing accurate dose planning by using the CT information in several steps of the dose planning calculation chain. This paper discusses the dosimetry chain used for individual absorbed-dose planning and highlights the areas where hybrid imaging makes significant contributions. PMID- 26854158 TI - Evaluation of Alpha-Therapy with Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer-the Role of Gamma Scintigraphy in Dosimetry and Pharmacokinetics. AB - Radium-223-dichloride ((223)RaCl2) is a new bone-seeking calcium analogue alpha emitter, which has obtained marketing authorization for the treatment skeletal metastases of hormone-refractory prostate cancer. The current treatment regimen is based on six consecutive doses of (223)RaCl2 at 4 week intervals and the administered activity dose, 50 kBq/kg per cycle is based on patient weight. We analyzed two patients using quantitative serial gamma imaging to estimate dosimetry in tumors and see possible pharmacokinetic differences in the treatment cycles. The lesions were rather well visualized in gamma scintigraphy in spite of low gamma activity (<1.1% gamma radiation) at 0, 7 and 28 days using 30-60 min acquisition times. Both our patients analyzed in serial gamma imagings, had two lesions in the gamma imaging field, the mean counts of the relative intensity varied from 27.8 to 36.5 (patient 1), and from 37.4 to 82.2 (patient 2). The half lives varied from 1.8 days to 4.5 days during the six cycles (patient 1), and from 1.5 days to 3.6 days (patient 2), respectively. In the lesion half-lives calculated from the imaging the maximum difference between the treatment cycles in the same lesion was 2.0-fold (1.8 vs. 3.6). Of these patients, patient 1 demonstrated a serum PSA response, whereas there was no PSA response in patient 2. From our data, there were maximally up to 4.0-fold differences (62.1 vs. 246.6 ) between the relative absorbed radiation doses between patients as calculated from the quantitative standardized imaging to be delivered in only two lesions, and in the same lesion the maximum difference in the cycles was up to 2.3-fold (107.4 vs. 246.6). Our recommendation based on statistical simulation analysis, is serial measurement at days 0-8 at least 3 times, this improve the accuracy significantly to study the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the imaging. Both our patients had originally two metastatic sites in the imaging field; the former patient demonstrated a serum PSA response and the latter demonstrated no PSA response. In these two patients there was no significant difference in the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the quantitative imaging. Our results, although preliminary, suggest that dose monitoring can be included as a part of this treatment modality. On the other hand, from the absorbed radiation doses, the response cannot be predicted because with very similar doses, only the former patient responded. PMID- 26854151 TI - Circulating HMGB1 and RAGE as Clinical Biomarkers in Malignant and Autoimmune Diseases. AB - High molecular group box 1 (HMGB1) is a highly conserved member of the HMG-box family; abundantly expressed in almost all human cells and released in apoptosis; necrosis or by activated immune cells. Once in the extracellular space, HMGB1 can act as a danger associated molecular pattern (DAMP), thus stimulating or inhibiting certain functions of the immune system; depending on the "combinatorial cocktail" of the surrounding milieu. HMGB1 exerts its various functions through binding to a multitude of membrane-bound receptors such as TLR 2; -4 and -9; IL-1 and RAGE (receptor for advanced glycation end products); partly complex-bound with intracellular fragments like nucleosomes. Soluble RAGE in the extracellular space, however, acts as a decoy receptor by binding to HMGB1 and inhibiting its effects. This review aims to outline today's knowledge of structure, intra- and extracellular functions including mechanisms of release and finally the clinical relevance of HMGB1 and RAGE as clinical biomarkers in therapy monitoring, prediction and prognosis of malignant and autoimmune disease. PMID- 26854159 TI - Pelvic Actinomycosis Associated with an Intrauterine Contraceptive Device Demonstrated on F-18 FDG PET/CT. AB - A 44-year-old woman with a history of dysmenorrhea, obstipation, and low back pain was investigated for gynecological disorder. Physical examination indicated a "frozen pelvis". Ultrasound examination revealed the ovaries adherent to the uterus, bilateral ovarian cysts, and an intrauterine contraceptive device in situ, which reportedly had been in place for 19 years. Prior to a scheduled laparoscopy, the patient returned with oedema of the lower abdomen and legs, fatigue, and weight loss. Laboratory findings included elevated CA-125, anemia, leucocytosis and high C-reactive protein. Pelvic actinomycosis was subsequently diagnosed. We report the PET/CT appearance of this condition. PMID- 26854157 TI - PET/MRI in Oncological Imaging: State of the Art. AB - Positron emission tomography (PET) combined with magnetic resonance imaging (MRI) is a hybrid technology which has recently gained interest as a potential cancer imaging tool. Compared with CT, MRI is advantageous due to its lack of ionizing radiation, superior soft-tissue contrast resolution, and wider range of acquisition sequences. Several studies have shown PET/MRI to be equivalent to PET/CT in most oncological applications, possibly superior in certain body parts, e.g., head and neck, pelvis, and in certain situations, e.g., cancer recurrence. This review will update the readers on recent advances in PET/MRI technology and review key literature, while highlighting the strengths and weaknesses of PET/MRI in cancer imaging. PMID- 26854160 TI - Use of Molecular Imaging Markers of Glycolysis, Hypoxia and Proliferation ((18)F FDG, (64)Cu-ATSM and (18)F-FLT) in a Dog with Fibrosarcoma: The Importance of Individualized Treatment Planning and Monitoring. AB - Glycolysis, hypoxia, and proliferation are important factors in the tumor microenvironment contributing to treatment-resistant aggressiveness. Imaging these factors using combined functional positron emission tomography and computed tomography can potentially guide diagnosis and management of cancer patients. A dog with fibrosarcoma was imaged using (18)F-FDG, (64)Cu-ATSM, and (18)F-FLT before, during, and after 10 fractions of 4.5 Gy radiotherapy. Uptake of all tracers decreased during treatment. Fluctuations in (18)F-FDG and (18)F-FLT PET uptakes and a heterogeneous spatial distribution of the three tracers were seen. Tracer distributions partially overlapped. It appears that each tracer provides distinct information about tumor heterogeneity and treatment response. PMID- 26854161 TI - Contrast Enhanced MRI in the Diagnosis of HCC. AB - Hepatocellular carcinoma (HCC) is the 6th most common cancer worldwide. Imaging plays a critical role in HCC screening and diagnosis. Initial screening of patients at risk for HCC is performed with ultrasound. Confirmation of HCC can then be obtained by Computed Tomography (CT) or Magnetic Resonance Imaging (MRI), due to the relatively high specificity of both techniques. This article will focus on reviewing MRI techniques for imaging HCC, felt by many to be the exam of choice for HCC diagnosis. MRI relies heavily upon the use of gadolinium-based contrast agents and while primarily extracellular gadolinium-based contrast agents are used, there is an emerging role of hepatobiliary contrast agents in HCC imaging. The use of other non-contrast enhanced MRI techniques for assessing HCC will also be discussed and these MRI strategies will be reviewed in the context of the pathophysiology of HCC to help understand the MR imaging appearance of HCC. PMID- 26854162 TI - Scintigraphic Small Intestinal Transit Time and Defaecography in Patients with J Pouch. AB - Objective methods for examination of pouch function are warranted for a better understanding of the functional result and treatment of dysfunction. The objective of this study was to evaluate the results of scintigraphic intestinal transit time and defaecography compared to the results of pouch function, mucosal condition and a questionnaire on quality of life (QoL). This cross-sectional study included 21 patients. Scintigraphic transit time and defaecography was determined with the use of Tc-99m. Pouch function was assessed by number of bowel movements, pouch volume, and continence. Pouch mucosal condition was evaluated by endoscopy and histology. Median transit time was 189 min (105-365). Median ejection fraction at defaecography (EF) was 49% (3-77) and 62% (17-98) after first and second defecation. Median pouch volume was 223 mL (100-360). A median daily stool frequency of nine (4-25) was reported and three (14%) patients suffered from daytime incontinence. No patients had symptomatic or endoscopic pouchitis; however, the histology showed unspecific inflammation in 19 (90%) patients. There was no correlation between transit time, evacuation fraction (EF) and pouch function in univariate analysis. However, we found a high body mass index (BMI) and a low bowel movement frequency to be associated with a longer transit time by multivariate analysis. Scintigraphic determination of transit time and defaecography are feasible methods in patients with ileal pouch anal anastomosis, but the clinical relevance is yet doubtful. PMID- 26854163 TI - Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer Preliminary Results of the Response Evaluation Using F-18-Fluoride PET/CT. AB - The purpose of this study was to evaluate the outcome after Radium-223-dichloride ((223)RaCl2) treatment of patients with skeletal metastases of castration resistant prostate cancer using whole-body (18)F-Fluoride PET/CT. Sodium (18)F fluoride [(18)F]-NaF PET/CT was performed prior the treatment of (223)RaCl2, after the first cycle and after the sixth cycle. The skeletal metastases were analyzed quantitatively using modified PET response evaluation PERCIST criteria. The patients were also analyzed for S-PSA. All ten patients responded in [(18)F] NaF scans after 6 cycles, but interim analysis after the 1st cycle did not give additional information about the outcome. The S-PSA decrease correlated with [(18)F]-NaF response, only 1 patient demonstrated progressive disease, i.e., >25% increase in S-PSA values during (223)RaCl2. Our results (although preliminary) suggest that (18)F-Fluoride PET/CT is useful in the follow-up of castration resistant prostate cancer with skeletal metastases. PMID- 26854165 TI - Beyond Screening: Can the Mini-Mental State Examination be Used as an Exclusion Tool in a Memory Clinic? AB - This study explores whether the Mini-Mental State Examination (MMSE) could reliably exclude definite dementia and dementia-free cases from requiring more extensive neuropsychological investigations in memory clinic settings in Singapore. Patients with memory complaints referred for possible dementia underwent the MMSE, followed by standardized neuropsychological and clinical assessments which led to a consensus diagnosis. MMSE cut-off points were derived stratified for education (less and equal/above primary level). Results show that after education stratification, using an optimal Positive Likelihood Ratio (PLR) and optimal Negative Likelihood Ratio (NLR), a higher percentage of patients were correctly identified as having dementia or dementia-free, with minimal misclassification rate. The finding suggests the MMSE can be used to exclude patients not requiring full neuropsychological assessments in a memory clinic. PMID- 26854166 TI - Risk Factors for Possible Dementia Using the Hopkins Verbal Learning Test and the Mini-Mental State Examination in Shanghai. AB - Using a combination of the Hopkins Verbal Learning Test (HVLT) and the Mini Mental State Examination (MMSE), we investigated the prevalence of possible dementia (DEM) in community-dwelling elderly in Shanghai. Subsequently, we investigated significant risk factors for DEM and generated a DEM self-checklist for early DEM detection and case management. We found that among a total of 521 participants using a HVLT cut-off score of <19 and a MMSE cut-off score of <24, a total of 69 DEM cases were identified. Risk factors, such as advanced age (>=68 years), low education (no or primary level), self-reported history of hypertension, and self-reported subjective memory complaints (SMC) were significantly predictive of DEM. The presence of >=3 out of four of the above mentioned risk factors can effectively discriminate DEM cases from non-DEM subjects. PMID- 26854167 TI - Early Detection of Hepatocellular Carcinoma: How to Screen and Follow up Patients with Liver Cirrhosis According to the GERMAN S3 Guideline? AB - Hepatocellular carcinoma (HCC) is frequently detected in pre-existing liver cirrhosis, but can also develop without such pre-conditions. There is an increasing trend of HCC incidence worldwide. In patients with liver cirrhosis, HCC has become the leading cause of death. At diagnosis the tumor has very often reached an advanced stage and curative treatment options are missing. Thus, early diagnosis would help the patient and prevent increasing healthcare costs. In our review we will summarize the recommendations of the German S3 guideline for the early diagnosis of HCC and will discuss the current literature in this context. The reader will learn which diagnostic tools are available and in what order they can be usefully applied. Surveillance should be done with ultrasound by a skilled examiner, additional imaging at best with state-of-the-art dynamic magnetic resonance. PMID- 26854168 TI - Performance-Based Cognitive Screening Instruments: An Extended Analysis of the Time versus Accuracy Trade-off. AB - Early and accurate diagnosis of dementia is key to appropriate treatment and management. Clinical assessment, including the use of cognitive screening instruments, remains integral to the diagnostic process. Many cognitive screening instruments have been described, varying in length and hence administration time, but it is not known whether longer tests offer greater diagnostic accuracy than shorter tests. Data from several pragmatic diagnostic test accuracy studies examining various cognitive screening instruments in a secondary care setting were analysed to correlate measures of test diagnostic accuracy and test duration, building on the findings of a preliminary study. High correlations which were statistically significant were found between one measure of diagnostic accuracy, area under the receiver operating characteristic curve, and surrogate measures of test duration, namely total test score and total number of test items/questions. Longer cognitive screening instruments may offer greater accuracy for the diagnosis of dementia, an observation which has possible implications for the optimal organisation of dedicated cognitive disorders clinics. PMID- 26854164 TI - When Prostate Cancer Circulates in the Bloodstream. AB - Management of patients with prostate cancer is currently based on imperfect clinical, biological, radiological and pathological evaluation. Prostate cancer aggressiveness, including metastatic potential, remains difficult to accurately estimate. In an attempt to better adapt therapeutics to an individual (personalized medicine), reliable evaluation of the intrinsic molecular biology of the tumor is warranted, and particularly for all tumor sites (primary tumors and secondary sites) at any time of the disease progression. As a consequence of their natural tendency to grow (passive invasion) or as a consequence of an active blood vessel invasion by metastase-initiating cells, tumors shed various materials into the bloodstream. Major efforts have been recently made to develop powerful and accurate methods able to detect, quantify and/or analyze all these circulating tumor materials: circulating tumors cells, disseminating tumor cells, extracellular vesicles (including exosomes), nucleic acids, etc. The aim of this review is to summarize current knowledge about these circulating tumor materials and their applications in translational research. PMID- 26854170 TI - The Role of Diffusion-Weighted Imaging (DWI) in Locoregional Therapy Outcome Prediction and Response Assessment for Hepatocellular Carcinoma (HCC): The New Era of Functional Imaging Biomarkers. AB - Reliable response criteria are critical for the evaluation of therapeutic response in hepatocellular carcinoma (HCC). Current response assessment is mainly based on: (1) changes in size, which is at times unreliable and lag behind the result of therapy; and (2) contrast enhancement, which can be difficult to quantify in the presence of benign post-procedural changes and in tumors presenting with a heterogeneous pattern of enhancement. Given these challenges, functional magnetic resonance imaging (MRI) techniques, such as diffusion weighted imaging (DWI) have been recently investigated, aiding specificity to locoregional therapy response assessment and outcome prediction. Briefly, DWI quantifies diffusion of water occurring naturally at a cellular level (Brownian movement), which is restricted in multiple neoplasms because of high cellularity. Disruption of cellular integrity secondary to therapy results in increased water diffusion across the injured membranes. This review will provide an overview of the current literature on DWI therapy response assessment and outcome prediction in HCC following treatment with locoregional therapies. PMID- 26854171 TI - Prevalence of Behavioural and Psychological Symptoms of Dementia in Individuals with Learning Disabilities. AB - A review of 23 studies investigating the prevalence of Behavioural and psychological symptoms of dementia (BPSD) in the general and learning disability population and measures used to assess BPSD was carried out. BPSD are non cognitive symptoms, which constitute as a major component of dementia regardless of its subtype Research has indicated that there is a high prevalence of BPSD in the general dementia population. There are limited studies, which investigate the prevalence of BPSD within individuals who have learning disabilities and dementia. Findings suggest BPSDs are present within individuals with learning disabilities and dementia. Future research should use updated tools for investigating the prevalence of BPSD within individuals with learning disabilities and dementia. PMID- 26854169 TI - Imaging of HCC-Current State of the Art. AB - Early diagnosis of hepatocellular carcinoma (HCC) is crucial for optimizing treatment outcome. Ongoing advances are being made in imaging of HCC regarding detection, grading, staging, and also treatment monitoring. This review gives an overview of the current international guidelines for diagnosing HCC and their discrepancies as well as critically summarizes the role of magnetic resonance imaging (MRI) and computed tomography (CT) techniques for imaging in HCC. The diagnostic performance of MRI with nonspecific and hepatobililiary contrast agents and the role of functional imaging with diffusion-weighted imaging will be discussed. On the other hand, CT as a fast, cheap and easily accessible imaging modality plays a major role in the clinical routine work-up of HCC. Technical advances in CT, such as dual energy CT and volume perfusion CT, are currently being explored for improving detection, characterization and staging of HCC with promising results. Cone beam CT can provide a three-dimensional analysis of the liver with tumor and vessel characterization comparable to cross-sectional imaging so that this technique is gaining an increasing role in the peri procedural imaging of HCC treated with interventional techniques. PMID- 26854173 TI - Association between APOE epsilon4 Genotype and Memory Impairment in Elderly with Normal Global Cognitive Assessment. AB - AIM: Early prediction using cognitive evaluation tools that are less influenced by education level is beneficial for dementia screening. This study investigated the relationship between Word List Memory Immediate Recall (WLM IR) and the Saving Score (SS) with having the APOE epsilon4 risk allele in the elderly with normal global cognitive assessment. METHODS: A cross-sectional study on 105 subjects >=60 years with normal MMSE scores who met inclusion criteria. Memory impairment (MI) if: WLM IR score on the third trial <8 or an SS score <80%. RESULTS: The majority of the subjects were female (68.6%), 65 +/- 7.1 years, had undertaken formal education for <6 years (56.2%), had MI (81%), and the APOE epsilon4 genotype was detected in 24.8% of subjects. There was a significant relationship between APOE epsilon4 and lower WLMIR (p = 0.02, OR 7.92, CI 95% (1.00-62.38)). CONCLUSIONS: WLM IR score is lower in elderly people with the APOE epsilon4 despite their normal global cognitive assessment results, and these scores were not influenced by education level. Further research needs to confirm that the WLM IR can be used to screen for early dementia. PMID- 26854176 TI - Micro-CT scouting for transmission electron microscopy of human tissue specimens. AB - Transmission electron microscopy (TEM) provides sub-nanometre-scale details in volumetric samples. Samples such as pathology tissue specimens are often stained with a metal element to enhance contrast, which makes them opaque to optical microscopes. As a result, it can be a lengthy procedure to find the region of interest inside a sample through sectioning. We describe micro-CT scouting for TEM that allows noninvasive identification of regions of interest within a block sample to guide the sectioning step. In a tissue pathology study, a bench-top micro-CT scanner with 10 MUm resolution was used to determine the location of patches of the mucous membrane in osmium-stained human nasal scraping samples. Once the regions of interest were located, the sample block was sectioned to expose that location, followed by ultra-thin sectioning and TEM to inspect the internal structure of the cilia of the membrane epithelial cells with nanometre resolution. This method substantially reduced the time and labour of the search process from typically 20 sections for light microscopy to three sections with no added sample preparation. PMID- 26854172 TI - Role of Hybrid Brain Imaging in Neuropsychiatric Disorders. AB - This is a focused review of imaging literature to scope the utility of hybrid brain imaging in neuropsychiatric disorders. The review focuses on brain imaging modalities that utilize hybrid (fusion) techniques to characterize abnormal brain molecular signals in combination with structural and functional changes that have been observed in neuropsychiatric disorders. An overview of clinical hybrid brain imaging technologies for human use is followed by a selective review of the literature that conceptualizes the use of these technologies in understanding basic mechanisms of major neuropsychiatric disorders and their therapeutics. Neuronal network abnormalities are highlighted throughout this review to scope the utility of hybrid imaging as a potential biomarker for each disorder. PMID- 26854177 TI - Waiving in vivo studies for monoclonal antibody biosimilar development: National and global challenges. AB - Biosimilars are biological medicinal products that contain a version of the active substance of an already authorised original biological medicinal product (the innovator or reference product). The first approved biosimilar medicines were small proteins, and more recently biosimilar versions of innovator monoclonal antibody (mAb) drugs have entered development as patents on these more complex proteins expire. In September 2013, the first biosimilar mAb, infliximab, was authorised in Europe. In March 2015, the first biosimilar (ZarxioTM, filgrastim-sndz, Sandoz) was approved by the US Food and Drug Administration; however, to date no mAb biosimilars have been approved in the US. There are currently major differences between how biosimilars are regulated in different parts of the world, leading to substantial variability in the amount of in vivo nonclinical toxicity testing required to support clinical development and marketing of biosimilars. There are approximately 30 national and international guidelines on biosimilar development and this number is growing. The European Union's guidance describes an approach that enables biosimilars to enter clinical trials based on robust in vitro data alone; in contrast, the World Health Organization's guidance is interpreted globally to mean in vivo toxicity studies are mandatory. We reviewed our own experience working in the global regulatory environment, surveyed current practice, determined drivers for nonclinical in vivo studies with biosimilar mAbs and shared data on practice and study design for 25 marketed and as yet unmarketed biosimilar mAbs that have been in development in the past 5y. These data showed a variety of nonclinical in vivo approaches, and also demonstrated the practical challenges faced in obtaining regulatory approval for clinical trials based on in vitro data alone. The majority of reasons for carrying out nonclinical in vivo studies were not based on scientific rationale, and therefore the authors have made recommendations for a data-driven approach to the toxicological assessment of mAb biosimilars that minimises unnecessary use of animals and can be used across all regions of the world. PMID- 26854178 TI - Validation of the Greek version of the device subscale of the Quebec User Evaluation of Satisfaction with Assistive Technology 2.0 (QUEST 2.0). AB - The purpose of the study was to evaluate the device subscale of the QUEST 2.0 instrument and provide evidence for the validity and reliability of the Greek version. To this end, a cross-cultural adaptation was performed. Field test studies were conducted to validate the appropriateness of the final outcome. Data were drawn from a study of 115 subjects who had been administered the GR-QUEST questionnaire. Ratings related to the different items were statistically analyzed. The exploratory factor analysis with varimax rotation conducted revealed a three factors structure of the device subscale in contrast with previous studies. Our "Safe Use" subscale contains the items adjustments, safety and effectiveness of the original instrument, the "Fit to Use" subscale contains the dimensions, weight and ease of use items, and the "Endurance" subscale contains the items durability and comfort of the original questionnaire. Reliability measures (ICC=0.949, Pearson's correlation=0.903, Cronbach's alpha=0.754) yielded high values. Test-retest outcome showed great stability. Based on the results, the GR-QUEST can be considered as a valid and reliable instrument and thus it can be used to measure the satisfaction of patients with assistive devices, while it is applicable to the Greek population. Further assessment of the services subscale is needed. PMID- 26854179 TI - Can breeder reproductive status, performance and egg quality be enhanced by supplementation and transition of n-3 fatty acids? AB - The aim of this experiment was to investigate the effect of n-3 fatty acid (FA) supplemented diets on breeder performance, productivity and egg quality. Breeders (n = 480) were fed the supplemented diet from 18 weeks onwards; the inclusion level of n-3 FA was increased from 1.5% to 3.0% from 34 weeks of age onwards until 48 weeks of age. Ross-308 broiler breeders (n = 480) were fed one of four different diets: a basal diet rich in n-6 FA (control diet) or one of three diets rich in n-3 FA. For the n-3 FA diets, eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) were fed to the broiler breeders at different ratios formulated to obtain EPA/DHA ratios of 1/1, 1/2 or 2/1. Differences in performance, reproduction and egg quality parameters due to n-3 supplementation were noted more for the 1.5% followed by the 3.0% fed broilers than their 1.5% supplemented counterparts. Egg weight (p < 0.001) and egg mass (p = 0.003) were significantly lower and feed conversion (p = 0.008) significantly higher for the n-3 FA (at 3.0% inclusion level) fed broilers compared to the control group. For the EPA- and DHA-fed breeders, a higher proportional abdominal fat percentage (p = 0.025) and proportional albumen weight (%) (p = 0.041) were found respectively. Dietary treatments did not affect reproduction. It can be concluded that the results of the present experiment indicate no significant differences between treatments at 1.5% inclusion levels. However, increasing this level to 3.0% is not recommended due to the rather negative effects on the measured parameters. It should be further investigated whether these adverse effects were obtained due to (i) the higher supplementation level, (ii) combining a supplementation level of 1.5% with 3% or (iii) the duration of supplementation. PMID- 26854180 TI - Diclofenac pretreatment effects on the toll-like receptor 4/nuclear factor kappa B-mediated inflammatory response to eccentric exercise in rat liver. AB - Acute exercise is a stress stimulus that may cause cell damage through the activation of the toll-like receptor (TLR)4 pathway, resulting in the translocation of nuclear factor kappa B (NF-kappaB) into the cell nucleus and the upregulation of inflammatory genes. Nonsteroidal anti-inflammatory drugs, such as diclofenac, are often prescribed to counteract exercise-induced inflammation. AIMS: This study analyzed effects of diclofenac pretreatment on the TLR4/NF kappaB pathway in rat liver after an acute eccentric exercise. MAIN METHODS: Twenty male Wistar rats were divided in four groups: control-saline, control diclofenac, exercise-saline and exercise-diclofenac. The rats received saline or diclofenac (10mg/kg) for 7days prior to an eccentric exercise bout. KEY FINDINGS: After exercise there was an increase in TLR4, myeloid differentiation primary response gene 88 (MyD88), TIR domain-containing adaptor inducing interferon (TRIF) and p65 NF-kappaB subunit protein levels. Exercise also resulted in increased mRNA and protein expression of interleukin (IL)-6, inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-alpha. Proinflammatory effects of exercise were prevented by the administration of diclofenac, which blunted the activation of the TLR4/NF-kappaB pathway and the inflammatory response in the liver of exercised rats. SIGNIFICANCE: Results from the present study highlight the role of TLR4 as a target for anti-inflammatory interventions. PMID- 26854181 TI - Deficient attention modulation of lateralized alpha power in schizophrenia. AB - Modulation of 8-14 Hz (alpha) activity in posterior brain regions is associated with covert attention deployment in visuospatial tasks. Alpha power decrease contralateral to to-be-attended stimuli is believed to foster subsequent processing, such as retention of task-relevant input. Degradation of this alpha regulation mechanism may reflect an early stage of disturbed attention regulation contributing to impaired attention and working memory commonly found in schizophrenia. The present study tested this hypothesis of early disturbed attention regulation by examining alpha power modulation in a lateralized cued delayed response task in 14 schizophrenia patients (SZ) and 25 healthy controls (HC). Participants were instructed to remember the location of a 100-ms saccade target cue in the left or right visual hemifield in order to perform a delayed saccade to that location after a retention interval. As expected, alpha power decrease during the retention interval was larger in contralateral than ipsilateral posterior regions, and SZ showed less of this lateralization than did HC. In particular, SZ failed to show hemifield-specific alpha modulation in posterior right hemisphere. Results suggest less efficient modulation of alpha oscillations that are considered critical for attention deployment and item encoding and, hence, may affect subsequent spatial working memory performance. PMID- 26854182 TI - An ASGCT Perspective on the National Academies Genome Editing Summit. PMID- 26854185 TI - Neurite outgrowth in human induced pluripotent stem cell-derived neurons as a high-throughput screen for developmental neurotoxicity or neurotoxicity. AB - Due to the increasing prevalence of neurological disorders and the large number of untested compounds in the environment, there is a need to develop reliable and efficient screening tools to identify environmental chemicals that could potentially affect neurological development. Herein, we report on a library of 80 compounds screened for their ability to inhibit neurite outgrowth, a process by which compounds may elicit developmental neurotoxicity, in a high-throughput, high-content assay using human neurons derived from induced pluripotent stem cells (iPSC). The library contains a diverse set of compounds including those that have been known to be associated with developmental neurotoxicity (DNT) and/or neurotoxicity (NT), environmental compounds with unknown neurotoxic potential (e.g., polycyclic aromatic hydrocarbons (PAHs) and flame retardants (FRs)), as well as compounds with no documented neurotoxic potential. Neurons were treated for 72h across a 6-point concentration range (~0.3-100MUM) in 384 well plates. Effects on neurite outgrowth were assessed by quantifying total outgrowth, branches, and processes. We also assessed the number ofviable cells per well. Concentration-response profiles were evaluated using a Hill model to derive benchmark concentration (BMC) values. Assay performance was evaluated using positive and negative controls and test replicates. Compounds were ranked by activity and selectivity (i.e., specific effects on neurite outgrowth in the absence of concomitant cytotoxicity) and repeat studies were conducted to confirm selectivity. Among the 80 compounds tested, 38 compounds were active, of which 16 selectively inhibited neurite outgrowth. Of these 16 compounds, 12 were known to cause DNT/NT and the remaining 4 compounds included 3 PAHs and 1 FR. In independent repeat studies, 14/16 selective compounds were reproducibly active in the assay, of which only 6 were selective for inhibition of neurite outgrowth. These 6 compounds were previously shown in the literature to be neurotoxic. These studies shed light on the current status of human iPSCs in DNT/NT screening and their utility in identifying, ranking, and prioritizing compounds with DNT/NT potential for further in vivo testing. PMID- 26854186 TI - Behaviour, development and metal accumulation in striped marsh frog tadpoles (Limnodynastes peronii) exposed to coal mine wastewater. AB - Coal mining generates large quantities of complex effluent, and this often contains high levels of dissolved solids, suspended solids, metals, hydrocarbons, salts and other compounds. Substantial volumes of mine wastewater are periodically discharged into the environment, through both planned and accidental releases, and this raises concerns about the potential for adverse impacts on aquatic wildlife. There have been few attempts to explore sub-lethal effects of coal mine wastewater on amphibians compared to other organisms, and this is particularly true for Australian species. To address existing knowledge gaps, we exposed striped marsh frog (Limnodynastes peronii) tadpoles to 25, 50 and 100% coal mine wastewater collected from two holding dams (CMW1 and CMW2) located at an open cut mine in Central Queensland, Australia. The exposure lasted for four weeks, after which survival, growth and development, swimming behaviour, and concentrations of metals and metalloids in tail and liver tissues were assessed. Physico-chemical parameters varied considerably between sites, with higher turbidity, nutrients, total and dissolved organic carbon, alkalinity and arsenic (As) concentrations at CMW1, and higher conductivity, salinity, dissolved solids, hardness and sulfate levels at CMW2. There was no mortality in controls and less than 5% mortality in CMW1 treatments, whereas survival was significantly decreased in tadpoles exposed to CMW2 with 40 and 55% mortality in the 50 and 100% treatments, respectively. Development was significantly delayed in 100% CMW1 wastewater, but tadpole size (growth) was not influenced by the exposure. Hepatosomatic indices were significantly increased in tadpoles exposed to 25 and 50% CMW1 but not the 100% treatment group. Exposed tadpoles (predominantly those exposed to CMW1) exhibited increased activity after very short-term exposure (24h), but this did not persist as animals approached metamorphic climax. At the end of the experiment, tadpoles exposed to both wastewaters had elevated levels of selenium (Se), cobalt (Co) and As in tail and liver tissue compared to controls. Manganese (Mn) levels were also elevated in livers and tails of CMW2 exposed tadpoles. Hepatic tissue accumulated 8-9 times higher concentrations of Co, Mn and Se compared to tail tissue, irrespective of treatments. Future research is warranted to explore possible relationships between metal bioaccumulation, morpho-physiological effects during development, and subsequent higher-level outcomes related to individual performance and population fitness. PMID- 26854187 TI - Termites utilise clay to build structural supports and so increase foraging resources. AB - Many termite species use clay to build foraging galleries and mound-nests. In some cases clay is placed within excavations of their wooden food, such as living trees or timber in buildings; however the purpose for this clay is unclear. We tested the hypotheses that termites can identify load bearing wood, and that they use clay to provide mechanical support of the load and thus allow them to eat the wood. In field and laboratory experiments, we show that the lower termite Coptotermes acinaciformis, the most basal species to build a mound-nest, can distinguish unloaded from loaded wood, and use clay differently when eating each type. The termites target unloaded wood preferentially, and use thin clay sheeting to camouflage themselves while eating the unloaded wood. The termites attack loaded wood secondarily, and build thick, load-bearing clay walls when they do. The termites add clay and build thicker walls as the load-bearing wood is consumed. The use of clay to support wood under load unlocks otherwise unavailable food resources. This behaviour may represent an evolutionary step from foraging behaviour to nest building in lower termites. PMID- 26854188 TI - [Small airway diseases and immune deficiency]. AB - INTRODUCTION: Innate or acquired immune deficiency may show respiratory manifestations, often characterized by small airway involvement. The purpose of this article is to provide an overview of small airway disease across the major causes of immune deficiency. BACKGROUND: In patients with common variable immune deficiency, recurrent lower airway infections may lead to bronchiolitis and bronchiectasis. Follicular and/or granulomatous bronchiolitis of unknown origin may also occur. Bronchiolitis obliterans is the leading cause of death after the first year in patients with lung transplantation. Bronchiolitis obliterans also occurs in patients with allogeneic haematopoietic stem cell transplantation, especially in the context of systemic graft-versus-host disease. VIEWPOINT AND CONCLUSION: Small airway diseases have different clinical expression and pathophysiology across various causes of immune deficiency. A better understanding of small airways disease pathogenesis in these settings may lead to the development of novel targeted therapies. PMID- 26854189 TI - Identifying Factors and Techniques to Decrease the Positive Margin Rate in Partial Mastectomies: Have We Missed the Mark? AB - Breast conservation therapy (BCT) has a reported incidence of positive margins ranging widely in the literature from 20% to 70%. Efforts have been made to refine standards for partial mastectomy and to predict which patients are at highest risk for incomplete excision. Most have focused on histology and demographics. We sought to further define modifiable risk factors for positive margins and residual disease. A retrospective study was conducted of 567 consecutive partial mastectomies by 21 breast and general surgeons from 2009 to 2012. Four hundred fourteen cases of neoplasm were reviewed for localization, intraoperative assessment, excision technique, rates, and results of re excision/mastectomy. Histologic margins were positive in 23% of patients, 25% had margins 0.1-0.9 mm, and 7% had tumor within 1-1.9 mm. Residual tumor was identified at-in 61 cases: 38% (disease at margin), 21% (0.1-0.9 mm), and 14% (1 1.9 mm). Ductal carcinoma in situ (DCIS) was present in 85% of residual disease on re-excision and correlated to higher rates of re-excision (p = <0.001), residual disease, and subsequent mastectomy. The use of multiple needles to localize neoplasms was associated with 2-3 times the likelihood for positive margins than when a single needle was required. The removal of additional margins at initial surgery correlated with improved rates of complete excision when DCIS was present. Patients must have careful analysis of specimen margins at the time of surgery and may benefit from additional tissue excision or routine shaving of the cavity of resection. Surgeons should conduct careful patient selection for BCT, in the context of multifocal, and multicentric disease. Patients for whom tumor localization requires bracketing may be at higher risk for positive margins and residual disease and should be counseled accordingly. PMID- 26854190 TI - Friendly Fire--The Bane of Thermal Ablation. PMID- 26854191 TI - Commentary on 50 years of research at the NBRL, Boston, Massachusetts. AB - Research at the NBRL, Boston, MA over the past 50 years assessed the survival and function of RBC and platelets and the function of plasma clotting proteins. Liquid preserved RBC can be stored at 4 degrees C for only 2 weeks to maintain a 24-hour posttransfusion survival value of 75%, moderately impaired oxygen transport function after transfusion, exert a hemostatic effect, and increase the plasma volume. Liquid preserved platelets can be stored at room temperature with agitation for only 2 days to have acceptable in vivo survival 2 hours following transfusion, normal lifespan, and a hemostatic effect to reduce the bleeding time in thrombocytopenic patients. RBCs frozen with 40% W/V glycerol at -80 degrees C for at least 10 years, thawed, and deglycerolized in the Haemonetics ACP215 can be stored in Nutricel at 4 degrees C for 2 weeks with a 24-hour posttransfusion survival of 75%, moderately impaired oxygen transport function after transfusion, exert a hemostatic effect and increase the plasma volume. Leukoreduced single donor platelets treated with 6% DMSO, the supernatant DMSO removed prior to freezing at -80 degrees C for 2 years, thawed, and diluted with 0.9% NaCl or AB plasma have a bimodal population of platelets: one population has reduced in vivo survival, but increased hemostatic effect and the other has normal in vivo survival. AB plasma can be stored at -80 degrees C for at least 14 years, thawed, and stored at 4 degrees C for 24 hours with acceptable in vitro function of clotting proteins. The data reported by the NBRL, Boston, Mass. over the past 50 years and the 15-year experience by the Netherlands military now recommend that FDA, ARC, HHS and DOD should support the use of universal donor frozen group O Rh positive and group O Rh negative RBC, frozen group O platelets and frozen AB plasma from male donors. The frozen blood products will eliminate the severe adverse events of mortality and morbidity associated with the current FDA approved red blood cell products, platelet products, and plasma. PMID- 26854192 TI - Predominance of DR3 in Somali children with type 1 diabetes in the twin cities, Minnesota. AB - BACKGROUND: Minnesota is home to the largest Somali population in USA, and pediatric diabetes teams are seeing increasing numbers of Somali children with diabetes. OBJECTIVE: To assess the immune basis of diabetes in Somali children in the Twin Cities, Minnesota. METHODS: A total of 31 Somali children <=19 yr were treated for type 1 diabetes (T1D) at the University of Minnesota Masonic Children's Hospital and Children's Hospitals and Clinics of Minnesota underwent analysis of human leukocyte antigen (HLA) alleles (n = 30) and diabetes autoantibodies [glutamic acid decarboxylase (GAD65), islet antigen 2 (IA-2), zinc transporter 8 (ZnT8); n = 31]. HLA alleles were analyzed in 49 Somalis without diabetes (controls). Anti-transglutaminase autoantibodies (TGA) for celiac disease were also measured. RESULTS: In Somali children with T1D aged 13.5 +/- 5 yr (35% female, disease duration 6.5 +/- 3.6 yr), the most common HLA allele was DRB1*03:01 (93%, compared with 45% of Somali controls), followed by DRB1*13:02 (27%). There was a relatively low frequency of DR4 (13%). Controls showed a similar pattern. All 31 participants were positive for at least one diabetes autoantibody. Insulin antibodies were positive in 84% (all were on insulin). Excluding insulin antibodies, 23 (74%) subjects tested positive for at least one other diabetes autoantibody; 32% had 1 autoantibody, 32% had 2 autoantibodies, and 10% had 3 autoantibodies. GAD65 autoantibodies were found in 56% of subjects, IA-2 in 29%, and ZnT8 in 26%. Four (13%) were TGA positive. CONCLUSION: The autoantibody and HLA profiles of Somali children with diabetes are consistent with autoimmune diabetes. Their HLA profile is unique with an exceptionally high prevalence of DRB1*03:01 allele and relative paucity of DR4 alleles compared with African Americans with T1D. PMID- 26854193 TI - Novel Osteogenic Ti-6Al-4V Device For Restoration Of Dental Function In Patients With Large Bone Deficiencies: Design, Development And Implementation. AB - Custom devices supporting bone regeneration and implant placement are needed for edentulous patients with large mandibular deficiencies where endosteal implantation is not possible. We developed a novel subperiosteal titanium aluminum-vanadium bone onlay device produced by additive manufacturing (AM) and post-fabrication osteogenic micro-/nano-scale surface texture modification. Human osteoblasts produced osteogenic and angiogenic factors when grown on laser sintered nano-/micro-textured surfaces compared to smooth surfaces. Surface processed constructs caused higher bone-to-implant contact, vertical bone growth into disk pores (microCT and histomorphometry), and mechanical pull-out force at 5 and 10 w on rat calvaria compared to non surface-modified constructs, even when pre-treating the bone to stimulate osteogenesis. Surface-modified wrap-implants placed around rabbit tibias osseointegrated by 6 w. Finally, patient-specific constructs designed to support dental implants produced via AM and surface processing were implanted on edentulous mandibular bone. 3 and 8 month post operative images showed new bone formation and osseointegration of the device and indicated stability of the dental implants. PMID- 26854195 TI - A study to assess the influence of interprofessional point of care simulation training on safety culture in the operating theatre environment of a university teaching hospital. AB - Interprofessional point of care or in situ simulation is used as a training tool in our operating theatre directorate with the aim of improving crisis behaviours. This study aimed to assess the impact of interprofessional point of care simulation on the safety culture of operating theatres. A validated Safety Attitude Questionnaire was administered to staff members before each simulation scenario and then re-administered to the same staff members after 6-12 months. Pre- and post-training Safety Attitude Questionnaire-Operating Room (SAQ-OR) scores were compared using paired sample t-tests. Analysis revealed a statistically significant perceived improvement in both safety (p < 0.001) and teamwork (p = 0.013) climate scores (components of safety culture) 6-12 months after interprofessional simulation training. A growing body of literature suggests that a positive safety culture is associated with improved patient outcomes. Our study supports the implementation of point of care simulation as a useful intervention to improve safety culture in theatres. PMID- 26854194 TI - Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk. AB - Human milk (HM) contains regulatory biomolecules including miRNAs, the origin and functional significance of which are still undetermined. We used TaqMan OpenArrays to profile 681 mature miRNAs in HM cells and fat, and compared them with maternal peripheral blood mononuclear cells (PBMCs) and plasma, and bovine and soy infant formulae. HM cells and PBMCs (292 and 345 miRNAs, respectively) had higher miRNA content than HM fat and plasma (242 and 219 miRNAs, respectively) (p < 0.05). A strong association in miRNA profiles was found between HM cells and fat, whilst PBMCs and plasma were distinctly different to HM, displaying marked inter-individual variation. Considering the dominance of epithelial cells in mature milk of healthy women, these results suggest that HM miRNAs primarily originate from the mammary epithelium, whilst the maternal circulation may have a smaller contribution. Our findings demonstrate that unlike infant formulae, which contained very few human miRNA, HM is a rich source of lactation-specific miRNA, which could be used as biomarkers of the performance and health status of the lactating mammary gland. Given the recently identified stability, uptake and functionality of food- and milk-derived miRNA in vivo, HM miRNA are likely to contribute to infant protection and development. PMID- 26854196 TI - Sequential monitoring of Phase I dose expansion cohorts. AB - A relatively recent development in the design of Phase I dose-finding studies is the inclusion of expansion cohort(s), that is, the inclusion of several more patients at a level considered to be the maximum tolerated dose established at the conclusion of the 'pure' Phase I part. Little attention has been given to the additional statistical analysis, including design considerations, that we might wish to consider for this more involved design. For instance, how can we best make use of new information that may confirm or may tend to contradict the estimate of the maximum tolerated dose based on the dose escalation phase. Those patients included during the dose expansion phase may possess different eligibility criteria. During the expansion phase, we will also wish to have an eye on any evidence of efficacy, an aspect that clearly distinguishes such studies from the classical Phase I study. Here, we present a methodology that enables us to continue the monitoring of safety in the dose expansion cohort while simultaneously trying to assess efficacy and, in particular, which disease types may be the most promising to take forward for further study. The most elementary problem is where we only wish to take account of further toxicity information obtained during the dose expansion cohort, and where the initial design was model based or the standard 3+3. More complex set-ups also involve efficacy and the presence of subgroups. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26854197 TI - Intercellular Transport of Nanomaterials is Mediated by Membrane Nanotubes In Vivo. AB - So-called membrane nanotubes are cellular protrusions between cells whose functions include cell communication, environmental sampling, and protein transfer. It has been previously reported that systemically administered carboxyl modified quantum dots (cQDs) are rapidly taken up by perivascular macrophages in skeletal muscle of healthy mice. Expanding these studies, it is found, by means of in vivo fluorescence microscopy on the mouse cremaster muscle, rapid uptake of cQDs not only by perivascular macrophages but also by tissue-resident cells, which are localized more than 100 MUm distant from the closest vessel. Confocal microscopy on muscle tissue, immunostained for the membrane dye DiI, reveals the presence of continuous membranous structures between MHC-II-positive, F4/80 positive cells. These structures contain microtubules, components of the cytoskeleton, which clearly colocalize with cQDs. The cQDs are exclusively found inside endosomal vesicles. Most importantly, by using in vivo fluorescence microscopy, this study detected fast (0.8 MUm s(-1) , mean velocity), bidirectional movement of cQDs in such structures, indicating transport of cQD containing vesicles along microtubule tracks by the action of molecular motors. The findings are the first to demonstrate membrane nanotube function in vivo and they suggest a previously unknown route for the distribution of nanomaterials in tissue. PMID- 26854198 TI - Group A Streptococcus induces less p65 nuclear translocation and non-classical nuclear factor kappa B activation in macrophages, which possibly leads to a weaker inflammatory response. AB - OBJECTIVES: The aim of this study was to explore the pathogenic mechanism of group A Streptococcus (GAS) and to investigate how GAS evades phagocytosis by immune cells. METHODS: The classical inflammatory signaling pathway of macrophages infected with GAS was investigated by protein microarray, real-time PCR, Western blot, immunoprecipitation, and flow cytometry. RESULTS: GAS induced a lower level of inflammatory mediators in macrophages than either the Gram positive Staphylococcus aureus or the Gram-negative Escherichia coli. Therefore, the conventional inflammatory signal pathway was investigated. It was found that GAS and S. aureus induced both toll-like receptor (TLR)2 and TLR4 expression, while Gram-negative E. coli only activated TLR4 in RAW264.7 cells. Although MyD88, the main adaptor protein, was activated by the three pathogens, there was no difference in MyD88 expression in macrophages. Nuclear factor kappa B (NF kappaB) is the classical transcription factor of inflammatory signals, and the results of the present study showed that GAS, similar to E. coli, induced a weaker p65 nuclear translocation compared to S. aureus. Interestingly, GAS activated NF-kappaB by inducing p65-p52 heterodimer, but not the classical heterodimer of NF-kappaB (p65-p50), while E. coli activated NF-kappaB by inducing both p65-p50 and p65-p52 heterodimers. CONCLUSIONS: Compared to S. aureus and E. coli infection, GAS induced a weaker nuclear translocation and distinct combination of NF-kappaB subunits in macrophages, which probably leads to a weak inflammatory response. PMID- 26854199 TI - Rapid Spread of Zika Virus in The Americas--Implications for Public Health Preparedness for Mass Gatherings at the 2016 Brazil Olympic Games. AB - Mass gatherings at major international sporting events put millions of international travelers and local host-country residents at risk of acquiring infectious diseases, including locally endemic infectious diseases. The mosquito borne Zika virus (ZIKV) has recently aroused global attention due to its rapid spread since its first detection in May 2015 in Brazil to 22 other countries and other territories in the Americas. The ZIKV outbreak in Brazil, has also been associated with a significant rise in the number of babies born with microcephaly and neurological disorders, and has been declared a 'Global Emergency by the World Health Organization. This explosive spread of ZIKV in Brazil poses challenges for public health preparedness and surveillance for the Olympics and Paralympics which are due to be held in Rio De Janeiro in August, 2016. We review the epidemiology and clinical features of the current ZIKV outbreak in Brazil, highlight knowledge gaps, and review the public health implications of the current ZIKV outbreak in the Americas. We highlight the urgent need for a coordinated collaborative response for prevention and spread of infectious diseases with epidemic potential at mass gatherings events. PMID- 26854200 TI - Co-delivery of VEGF and bFGF via a PLGA nanoparticle-modified BAM for effective contracture inhibition of regenerated bladder tissue in rabbits. AB - Graft contracture is a common problem associated with the regeneration processes of tissue-engineered bladders. Currently, most strategies used for incorporating bioactive molecules into biomaterial designs do not work during all phases of tissue regeneration. In this study, we used a growth factor-PLGA nanoparticle thermo-sensitive gel system (i.e., BAM with incorporated VEGF and bFGF-loaded PLGA nanoparticles and mixed with a hydrophilic gel) to promote bladder tissue regeneration in a rabbit model. At 4 and 12 weeks after surgery, contracture rate assessment and histological examination were conducted to evaluate bladder tissue regeneration. The results indicated that the functional composite scaffold continuously and effectively released VEGF and bFGF and promoted bladder reconstruction with a significant decrease in graft contracture. In addition, the number and arrangement of regenerated urothelial cells and smooth muscle cells as well as microvascular density and maturity were improved in the VEGF/bFGF nanoparticle group compared with the single factor VEGF or bFGF nanoparticle group and BAM alone. The nanoparticle thermo-sensitive gel system, which exhibited favourable performance, may effectively inhibit graft contracture and promote bladder tissue regeneration in rabbits. PMID- 26854201 TI - Validation of a risk prediction score for proximal neoplasia in colorectal cancer screening: a prospective colonoscopy study. AB - This study developed a clinical scoring system to predict the risks of PN among screening participants for colorectal cancer. We recruited 5,789 Chinese asymptomatic screening participants who received colonoscopy in Hong Kong (2008 2014). From random sampling of 2,000 participants, the independent risk factors were evaluated for PN using binary regression analysis. The odds ratios for significant risk factors were used to develop a scoring system, with scores stratified into 'average risk' (AR):0-2 and 'high risk' (HR):3-5. The other 3,789 subjects formed an independent validation cohort. Each participant received a score calculated based on their risk factors. The performance of the scoring system was evaluated. The proportion of PN in the derivation and validation cohorts was 12.6% and 12.9%, respectively. Based on age, gender, family history, body mass index and self-reported ischaemic heart disease, 85.0% and 15.0% in the validation cohort were classified as AR and HR, respectively. Their prevalence of PN was 12.0% and 18.1%, respectively. Participants in the HR group had 1.51-fold (95% CI = 1.24-1.84, p < 0.001) higher risk of PN than the AR group. The overall c-statistics of the prediction model was 0.71(0.02). The scoring system is useful in predicting the risk of PN to prioritize patients for colonoscopy. PMID- 26854202 TI - Heart Rate Variability Change Before and After Hemodialysis is Associated with Overall and Cardiovascular Mortality in Hemodialysis. AB - Low heart rate variability (HRV) has been recognized to correlate with adverse cardiovascular (CV) outcomes in hemodialysis (HD) patients. It has been reported that HRV might be improved after HD, but whether the improved HRV after HD predicts a better CV prognosis remains to be determined. This study examined the ability of the change in HRV before and after HD in predicting overall and CV mortality in HD patients. This study enrolled 182 patients under maintenance HD. HRV was examined to assess changes before and after HD. The change in HRV (DeltaHRV) was defined as post-HD HRV minus pre-HD HRV. During a median follow-up period of 35.2 months, 29 deaths (15.9%) were recorded. Multivariate analysis showed that decreased DeltaLF% was associated with increased overall (hazard ratios [HR], 0.978; 95% confidence interval [CI], 0.961-0.996; p = 0.019) and CV mortality (HR, 0.941; 95% CI, 0.914-0.970; p < 0.001), respectively. Moreover, adding DeltaLF% to a clinical model provided an additional benefit in the prediction of overall (p = 0.002) and CV mortality (p < 0.001). HRV change before and after HD (DeltaHRV) is an useful clinical marker, and it is stronger than HRV before HD in predicting overall and CV mortality. PMID- 26854203 TI - Comparison of peripheral near-infrared spectroscopy low-frequency oscillations to other denoising methods in resting state functional MRI with ultrahigh temporal resolution. AB - PURPOSE: Functional MRI (fMRI) blood-oxygen level-dependent (BOLD) signals result not only from neuronal activation, but also from nonneuronal physiological processes. These changes, especially in the low-frequency domain (0.01-0.2 Hz), can significantly confound inferences about neuronal processes. It is crucial to effectively identify these nuisance low-frequency oscillations (LFOs). METHOD: A high temporal resolution (repetition time, ~0.5 s) fMRI resting state study was conducted with simultaneous physiological measurements to compare LFOs measured directly by near-infrared spectroscopy (NIRS) in the periphery and three methods that model LFOs from the respiration or cardiac signal: 1) the respiration volume per time (RVT), 2) the respiratory variation (RVRRF), and 3) the cardiac variation method (HRCRF). The LFO noise regressors from these methods were compared temporally and spatially as well as in their denoising efficiency. RESULTS: Methods were not highly correlated with one another, temporally or spatially. The set of two NIRS LFOs combined explained over 13% of BOLD signal variance and explained equal or more variance than HRCRF and RVRRF or RVT combined (in 14 of 16 participants). CONCLUSION: LFOs collected using NIRS in the periphery contain distinct temporal and spatial information about the LFOs in BOLD fMRI that is not contained in current low-frequency denoising methods derived from respiration and cardiac pulsation. Magn Reson Med 76:1697-1707, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26854205 TI - Elevated fecal levels of eosinophil granule proteins predict collagenous colitis in patients referred to colonoscopy due to chronic non-bloody diarrhea. AB - OBJECTIVE: Colonoscopy with biopsy sampling is often performed to detect collagenous colitis (CC) and lymphocytic colitis (LC) in patients with chronic non-bloody diarrhea. However, the diagnostic yield is low and incurs high costs. Fecal calprotectin (FC) and myeloperoxidase (MPO) indicate intestinal inflammation in ulcerative colitis (UC) and Crohn's disease (CD). In CC, elevated fecal levels of eosinophil protein X (EPX) and eosinophil cationic protein (ECP) have been reported. We aimed to evaluate if F-EPX, F-ECP, FC, and F-MPO could predict the diagnostic outcome in patients with chronic non-bloody diarrhea referred to colonoscopy. We also evaluated serum (S) EPX and ECP in this regard. METHODS: Of 67 included patients, 63 (94%) underwent colonoscopy with biopsy sampling. Fecal EPX, F-ECP, FC, F-MPO, S-EPX, and S-ECP were analyzed. RESULTS: Diagnostic outcome: normal: n = 46 (73%), CC: n = 9 (14%), LC: n = 4 (6%), UC: n = 2 (3%), CD: n = 2 (3%). Higher levels of F-EPX and F-ECP were found in CC compared to a normal diagnostic outcome (p = 0.01). No change was noted in any of the fecal markers in LC. When all of the fecal markers were normal the probability of a normal diagnostic outcome was 92%. We found no differences in S EPX and S-ECP between the groups. CONCLUSION: Elevated F-EPX and F-ECP could predict CC. None of the fecal markers predicted LC. Serum-EPX and S-ECP are not useful for the diagnosis of CC, LC, UC, or CD. With normal levels in all of the analyzed fecal markers, there is a low probability of a pathologic diagnostic outcome. PMID- 26854204 TI - Lysophosphatidic acid activates Arf6 to promote the mesenchymal malignancy of renal cancer. AB - Acquisition of mesenchymal properties by cancer cells is critical for their malignant behaviour, but regulators of the mesenchymal molecular machinery and how it is activated remain elusive. Here we show that clear cell renal cell carcinomas (ccRCCs) frequently utilize the Arf6-based mesenchymal pathway to promote invasion and metastasis, similar to breast cancers. In breast cancer cells, ligand-activated receptor tyrosine kinases employ GEP100 to activate Arf6, which then recruits AMAP1; and AMAP1 then binds to the mesenchymal-specific protein EPB41L5, which promotes epithelial-mesenchymal transition and focal adhesion dynamics. In renal cancer cells, lysophosphatidic acid (LPA) activates Arf6 via its G-protein-coupled receptors, in which GTP-Galpha12 binds to EFA6. The Arf6-based pathway may also contribute to drug resistance. Our results identify a specific mesenchymal molecular machinery of primary ccRCCs, which is triggered by a product of autotaxin and it is associated with poor outcome of patients. PMID- 26854206 TI - Successful Vitrification of In vivo Embryos Collected from Superovulated Japanese Black Cattle (Wagyu). AB - The aim of this study was to determine whether vitrification is an effective method when used for Japanese Black Cattle (Wagyu) in vivo-derived embryos, collected following a superovulation treatment and embryo transfer (MOET) programme. In vivo-derived morula and blastocysts collected on day 7 after artificial insemination, were vitrified using a modified droplet vitrification (MDV) procedure and subsequently warmed for transfer (ET) into synchronized recipients. Fresh embryos, and embryos cryopreserved using a standardized slow freezing procedure (direct thaw/direct transfer, DT) served as ET controls. Two different follicle-stimulating hormone (FSH) sources, Folltropin((r)) Canada (FSH BAH, 24 donors) and a brand prepared by the Chinese Academy of Science (FSH CAS, 16 donors), were compared in a series of superovulation outcomes following well established FSH administration protocols. Following data analysis, the total number of ovulations recorded at the time of embryo flushing (10.5 vs 8.5; p = 0.28) and the total number of transferable embryos (6.2 vs 5.1; p = 0.52) were similar between the two FSH sources. ET for MDV (39.7%, n = 78), DT (35.2%, n = 71) and fresh controls (47.1%, n = 34) resulted in similar pregnancy rates (p > 0.05). When MDV was used, a higher pregnancy rate (42.6%) resulted from the transfer of vitrified morulae, when compared to the DT counterparts (24.3%), (p = 0.05). Transfer of vitrified morulae resulted also in higher pregnancy rate, when compared to the transfer of vitrified blastocysts (42.6% vs. 29.4%; p < 0.05). Transfer of DT blastocysts resulted in higher pregnancy rate than morulae, similarly cryopreserved (47.1% vs. 24.3%, p < 0.05). In conclusion, MDV is an effective alternative methodology for cryopreservation of in vivo-derived embryos. This study gives also indication that, compared to vitrified blastocysts, MDV of morula stage embryos results in higher pregnancy rates following warming and transfer into synchronized recipients. PMID- 26854207 TI - What Parents Want: Does Provider Knowledge of Written Parental Expectations Improve Satisfaction in the Emergency Department? AB - OBJECTIVE: Satisfaction is an important measure of care quality. Interventions to improve satisfaction in the pediatric emergency department (ED) are limited, especially for patients with nonurgent conditions. Our objective was to determine if clinician knowledge of written parental expectations improves parental satisfaction for nonurgent ED visits. METHODS: This randomized controlled trial was conducted in a tertiary-care pediatric ED. Parents of children presenting for nonurgent visits (Emergency Severity Index level 4 or 5) were randomized into 3 groups: 1) the intervention group completed an expectation survey on arrival, which was reviewed by the clinician, 2) the control group completed the expectation survey, which was not reviewed, and 3) the baseline group did not complete an expectation survey. At ED disposition, all groups completed a 3-item satisfaction survey, scored using 5-point Likert scales (1 = very poor, 5 = very good). The primary outcome was rating of "overall care." Secondary outcomes included likelihood of recommending the ED and staff sensitivity to concerns. Proportions were compared by chi-square test. RESULTS: A total of 304 subjects were enrolled. The proportion of parents rating 5 of 5 for overall care did not differ among the baseline, control, and intervention groups (74.8% vs 73.2% vs 69.2%, P = .56). The proportion of parents rating 5 of 5 also did not differ for likelihood of recommending the ED (77.7% vs 72.2% vs 70.2%, P = .45) or staff sensitivity to concerns (78.6% vs 78.4% vs 78.8%, P = .71). CONCLUSIONS: For nonurgent pediatric ED visits, clinician knowledge of written parental expectations does not improve parental satisfaction. PMID- 26854208 TI - Hospital Variation in Cervical Spine Imaging of Young Children With Traumatic Brain Injury. AB - OBJECTIVE: Cervical imaging practices are poorly understood in young children with traumatic brain injury (TBI). We therefore sought to identify child-level and hospital-level factors associated with performance of cervical imaging of children with TBI from falls and abusive head trauma (AHT) and to describe across hospital variation in cervical imaging performance. We hypothesized that imaging decisions would be influenced by hospital volume of young injured children. METHODS: We performed a retrospective study of children younger than 2 years of age with TBI from 2009 to 2013 in the Premier Perspective Database. After adjustment for observed patient characteristics, we evaluated variation in advanced cervical imaging (computed tomography or magnetic resonance imaging) in children with AHT and TBI from falls. RESULTS: Of 2347 children with TBI, 18.7% were from abuse and 57.1% were from falls. Fifteen percent of children with TBI underwent advanced cervical imaging. Moderate or severe head injuries were associated with increased odds of cervical imaging in AHT (odds ratio 7.10; 95% confidence interval 2.75, 18.35) and falls (odds ratio 2.25; 95% confidence interval 1.19, 4.27). There was no association between annual hospital volume of injured children and cervical imaging performance. The adjusted probability of imaging across hospitals ranged from 4.3% to 84.3% in AHT and 3.1 to 39.0% in TBI from falls (P < .001). CONCLUSIONS: These results highlight variation across hospitals in adjusted probability of cervical imaging in AHT (nearly 20-fold) and TBI from falls (over 10-fold) not explained by observed patient characteristics. This variation suggests opportunities for further research to inform imaging practices. PMID- 26854209 TI - Rupture of Abdominal Aortic Aneurysms in Patients Under Screening Age and Elective Repair Threshold. AB - OBJECTIVES: The objective of this study was to identify the proportion of abdominal aortic aneurysm ruptures that occur before the screening age or threshold diameter for operative repair is reached. METHODS: The study was a retrospective analysis of RAAA patients including all RAAA patients admitted to Helsinki (HUH) and Tampere University Hospitals (TaUH) during 2002-2013. The data for age, gender, and comorbidities were collected from vascular registry and patient records. Computed tomography images taken at the time of admission were used for the measurement of maximum anteroposterior (AP) aneurysm diameter at the time of rupture. Age and diameter data were compared with risk factors. RESULTS: A total of 585 patients diagnosed with RAAA were admitted to the two hospitals during the 12 year period. The mean age at the time of rupture was 73.6 years (SD 9.5, range 42-96 years). 18.3% of patients were under 65: 21.4% of men and 3.0% of women. Men were on average 8 years younger than women. The odds ratio (OR) for rupture before 65 years of age for smokers was 2.1 compared with non-smokers, and 28.4% of smokers were under 65 at the time of rupture. Of all RAAA patients, 327 had a computed tomography scan confirming rupture. The mean AP diameter of the aneurysm was 75.6 mm (SD 15.8, range 32-155 mm). The mean size was significantly lower in women than in men (70.5 vs. 76.8, p = .005). CONCLUSIONS: The data from this study show that a fifth of men would not make it to the screening age of 65 before AAA rupture, the proportion being even larger in active smokers. The data from this study also supports the previous finding that aneurysm size at the time of rupture is significantly smaller in women. PMID- 26854210 TI - Re. "Contrast Induced Nephropathy and Long-term Renal Decline After Percutaneous Transluminal Angioplasty for Symptomatic Peripheral Arterial Disease". PMID- 26854211 TI - Neuronal and glial expression of inward rectifier potassium channel subunits Kir2.x in rat dorsal root ganglion and spinal cord. AB - Inward rectifier K(+) channels of the Kir2.x subfamily play important roles in controlling the neuronal excitability. Although their cellular localization in the brain has been extensively studied, only a few studies have examined their expression in the spinal cord and peripheral nervous system. In this study, immunohistochemical analyses of Kir2.1, Kir2.2, and Kir2.3 expression were performed in rat dorsal root ganglion (DRG) and spinal cord using bright-field and confocal microscopy. In DRG, most ganglionic neurons expressed Kir2.1, Kir2.2 and Kir2.3, whereas satellite glial cells chiefly expressed Kir2.3. In the spinal cord, Kir2.1, Kir2.2 and Kir2.3 were all expressed highly in the gray matter of dorsal and ventral horns and moderately in the white matter also. Within the gray matter, the expression was especially high in the substantia gelatinosa (lamina II). Confocal images obtained using markers for neuronal cells, NeuN, and astrocytes, Sox9, showed expression of all three Kir2 subunits in both neuronal somata and astrocytes in lamina I-III of the dorsal horn and the lateral spinal nucleus of the dorsolateral funiculus. Immunoreactive signals other than those in neuronal and glial somata were abundant in lamina I and II, which probably located mainly in nerve fibers or nerve terminals. Colocalization of Kir2.1 and 2.3 and that of Kir2.2 and 2.3 were present in neuronal and glial somata. In the ventral horn, motor neurons and interneurons were also immunoreactive with the three Kir2 subunits. Our study suggests that Kir2 channels composed of Kir2.1-2.3 subunits are expressed in neuronal and glial cells in the DRG and spinal cord, contributing to sensory transduction and motor control. PMID- 26854212 TI - Role of antigen presentation in the production of pro-inflammatory cytokines in obese adipose tissue. AB - Type II diabetes regroups different physiological anomalies that ultimately lead to low-grade chronic inflammation, insulin resistance and loss of pancreatic beta cells. Obesity is one of the best examples of such a condition that can develop into Metabolic Syndrome, causing serious health problems of great socio-economic consequences. The pathological outcome of obesity has a genetic basis and depends on the delicate balance between pro- and anti-inflammatory effectors of the immune system. The causal link between obesity and inflammation is well established. While innate immunity plays a key role in the development of a pro inflammatory state in obese adipose tissues, it has now become clear that adaptive immune cells are also involved and participate in the cascade of events that lead to metabolic perturbations. The efficacy of some immunotherapeutic protocols in reducing the symptoms of obesity-driven metabolic syndrome in mice implicated all arms of the immune response. Recently, the production of pathogenic immunoglobulins and pro-inflammatory cytokines by B and T lymphocytes suggested an auto-immune basis for the establishment of a non-healthy obese state. Understanding the cellular landscape of obese adipose tissues and how immune cells sustain chronic inflammation holds the key to the development of targeted therapies. In this review, we emphasize the role of antigen-presenting cells and MHC molecules in obese adipose tissue and the general contribution of the adaptive arm of the immune system in inflammation-induced insulin resistance. PMID- 26854213 TI - TLR-signaling and proinflammatory cytokines as drivers of tumorigenesis. AB - The link between inflammation and cancer was first proposed by R. Virchow. It was later realized that it is chronic inflammation that may promote cancer, whereas acute inflammation can actually block tumor development or even result in cure. Many molecular mediators of these diverse processes have been characterized only during the past 3 decades thanks to the advances in molecular and cellular techniques, as well as due to technologies of reverse genetics. In this chapter we discuss the role of Toll-like receptor (TLR) 4 signaling in cancer and contributions of proinflammatory cytokine signaling (whose expression may be driven by TLR-mediated signals) to tumor-promoting microenvironment. We also discuss recent clinical advances to target these pro-tumorigenic pathways at distinct stages of tumorigenesis. PMID- 26854214 TI - Two cases of Vici syndrome associated with Idiopathic Thrombocytopenic Purpura (ITP) with a review of the literature. AB - Vici syndrome is a rare congenital disorder first described in 1988. To date, 31 cases have been reported in the literature. The characteristic features of this syndrome include: agenesis of the corpus callosum, albinism, cardiomyopathy, variable immunodeficiency, cataracts, and myopathy. We report two Hispanic sisters with genetically confirmed Vici syndrome who both developed Idiopathic Thrombocytopenic Purpura. To our knowledge, this is an immunologic process that has been previously undescribed within the phenotype of Vici syndrome and should be added to the spectrum of variable immune dysregulation that can be found in these patients. PMID- 26854215 TI - Microfluidic magnetic self-assembly at liquid-liquid interfaces. AB - We present a microfluidic method that controllably self-assembles microparticles into clusters at an aqueous two-phase liquid-liquid interface. The liquid-liquid interface is formed between converging flows of aqueous dextran and polyethylene glycol, in a microfluidic cross-slot device. We control the size of the self assembled particle clusters as they pass through the liquid-liquid interface, by systematically varying the applied magnetic field gradient, and the interfacial tension of the liquid-liquid interface. We find that upon penetration through the interface, the number of particles within a cluster increases with increasing interfacial tension, and decreasing magnetic field gradient. We also develop a scaling model of the number of particles within a cluster, and observe an inverse scaling of the number of particles within a cluster with the dimensionless magnetic Bond number. Upon cluster penetration across the liquid-liquid interface, we find magnetic Bond number regimes where the fluid coating drains away from the surface of the cluster, and where the clusters are encapsulated inside a thin film coating layer. This self-assembly technique may find application in controlling the size of microscale self-assemblies, and coating such assemblies; for example, in clustering and coating of cells for immunoisolated cell transplants. PMID- 26854216 TI - Life-threatening hemoptysis secondary to Rasmussen's aneurysm in an HIV patient. PMID- 26854217 TI - Point of care testing of phospholipase A2 group IIA for serological diagnosis of rheumatoid arthritis. AB - Secretory phospholipase A2 group IIA (sPLA2-IIA) was examined as a point of care marker for determining disease activity in rheumatoid (RA) and psoriatic (PsA) arthritis. Serum concentration and activity of sPLA2-IIA were measured using in house antibodies and a novel point of care lateral flow device assay in patients diagnosed with varying severities of RA (n = 30) and PsA (n = 25) and found to correlate strongly with C-reactive protein (CRP). Levels of all markers were elevated in patients with active RA over those with inactive RA as well as both active and inactive PsA, indicating that sPLA2-IIA can be used as an analogue to CRP for RA diagnosis at point of care. PMID- 26854218 TI - The Prozone Effect Accounts for the Paradoxical Function of the Cdk-Binding Protein Suc1/Cks. AB - Previous work has shown that Suc1/Cks proteins can promote the hyperphosphorylation of primed Cdk1 substrates through the formation of ternary Cdk1-Cks-phosphosubstrate complexes. This raises the possibility that Cks proteins might be able to both facilitate and interfere with hyperphosphorylation through a mechanism analogous to the prozone effect in antigen-antibody interactions, with substoichiometric Cks promoting the formation of Cdk1-Cks phosphosubstrate complexes and suprastoichiometric Cks instead promoting the formation of Cdk1-Cks and Cks-phosphosubstrate complexes. We tested this hypothesis through a combination of theory, proof-of-principle experiments with oligonucleotide annealing, and experiments on the interaction of Xenopus cyclin B1-Cdk1-Cks2 with Wee1A in vitro and in Xenopus extracts. Our findings help explain why both Cks under-expression and overexpression interfere with cell cycle progression and provide insight into the regulation of the Cdk1 system. PMID- 26854220 TI - Subcellular Imbalances in Synaptic Activity. AB - The dynamic interactions between synaptic excitation and inhibition (E/I) shape membrane potential fluctuations and determine patterns of neuronal outputs; however, the spatiotemporal organization of these interactions within a single cell is poorly understood. Here, we investigated the relationship between local synaptic excitation and global inhibition in hippocampal pyramidal neurons using functional dendrite imaging in combination with whole-cell recordings of inhibitory postsynaptic currents. We found that the sums of spine inputs over dendritic trees were counterbalanced by a proportional amount of somatic inhibitory inputs. This online E/I correlation was maintained in dendritic segments that were longer than 50 MUm. However, at the single spine level, only 22% of the active spines were activated with inhibitory inputs. This inhibition coupled activity occurred mainly in the spines with large heads. These results shed light on a microscopic E/I-balancing mechanism that operates at selected synapses and that may increase the accuracy of neural information. PMID- 26854219 TI - Systemic Reprogramming of Translation Efficiencies on Oxygen Stimulus. AB - Protein concentrations evolve under greater evolutionary constraint than mRNA levels. Translation efficiency of mRNA represents the chief determinant of basal protein concentrations. This raises a fundamental question of how mRNA and protein levels are coordinated in dynamic systems responding to physiological stimuli. This report examines the contributions of mRNA abundance and translation efficiency to protein output in cells responding to oxygen stimulus. We show that changes in translation efficiencies, and not mRNA levels, represent the major mechanism governing cellular responses to [O2] perturbations. Two distinct cap dependent protein synthesis machineries select mRNAs for translation: the normoxic eIF4F and the hypoxic eIF4F(H). O2-dependent remodeling of translation efficiencies enables cells to produce adaptive translatomes from preexisting mRNA pools. Differences in mRNA expression observed under different [O2] are likely neutral, given that they occur during evolution. We propose that mRNAs contain translation efficiency determinants for their triage by the translation apparatus on [O2] stimulus. PMID- 26854221 TI - The Gut Microbiota Modulates Energy Metabolism in the Hibernating Brown Bear Ursus arctos. AB - Hibernation is an adaptation that helps many animals to conserve energy during food shortage in winter. Brown bears double their fat depots during summer and use these stored lipids during hibernation. Although bears seasonally become obese, they remain metabolically healthy. We analyzed the microbiota of free ranging brown bears during their active phase and hibernation. Compared to the active phase, hibernation microbiota had reduced diversity, reduced levels of Firmicutes and Actinobacteria, and increased levels of Bacteroidetes. Several metabolites involved in lipid metabolism, including triglycerides, cholesterol, and bile acids, were also affected by hibernation. Transplantation of the bear microbiota from summer and winter to germ-free mice transferred some of the seasonal metabolic features and demonstrated that the summer microbiota promoted adiposity without impairing glucose tolerance, suggesting that seasonal variation in the microbiota may contribute to host energy metabolism in the hibernating brown bear. PMID- 26854222 TI - Synaptophysin 1 Clears Synaptobrevin 2 from the Presynaptic Active Zone to Prevent Short-Term Depression. AB - Release site clearance is an important process during synaptic vesicle (SV) recycling. However, little is known about its molecular mechanism. Here we identify self-assembly of exocytosed Synaptobrevin 2 (Syb2) and Synaptophysin 1 (Syp1) by homo- and hetero-oligomerization into clusters as key mechanisms mediating release site clearance for preventing cis-SNARE complex formation at the active zone (AZ). In hippocampal neurons from Syp1 knockout mice, neurons expressing a monomeric Syb2 mutant, or after acute block of the ATPase N ethylmaleimide-sensitive factor (NSF), responsible for cis-SNARE complex disassembly, we found strong frequency-dependent short-term depression (STD), whereas retrieval of Syb2 by compensatory endocytosis was only affected weakly. Defects in Syb2 endocytosis were stimulus- and frequency-dependent, indicating that Syp1 is not essential for Syb2 retrieval, but for its efficient clearance upstream of endocytosis. Our findings identify an SV protein as a release site clearance factor. PMID- 26854223 TI - Loss of Adipose Fatty Acid Oxidation Does Not Potentiate Obesity at Thermoneutrality. AB - Ambient temperature affects energy intake and expenditure to maintain homeostasis in a continuously fluctuating environment. Here, mice with an adipose-specific defect in fatty acid oxidation (Cpt2(A-/-)) were subjected to varying temperatures to determine the role of adipose bioenergetics in environmental adaptation and body weight regulation. Microarray analysis of mice acclimatized to thermoneutrality revealed that Cpt2(A-/-) interscapular brown adipose tissue (BAT) failed to induce the expression of thermogenic genes such as Ucp1 and Pgc1alpha in response to adrenergic stimulation, and increasing ambient temperature exacerbated these defects. Furthermore, thermoneutral housing induced mtDNA stress in Cpt2(A-/-) BAT and ultimately resulted in a loss of interscapular BAT. Although the loss of adipose fatty acid oxidation resulted in clear molecular, cellular, and physiologic deficits in BAT, body weight gain and glucose tolerance were similar in control and Cpt2(A-/-) mice in response to a high-fat diet, even when mice were housed at thermoneutrality. PMID- 26854225 TI - Gut-Colonizing Bacteria Promote C. elegans Innate Immunity by Producing Nitric Oxide. AB - Many commensal bacteria in the gut are beneficial to the host immune system, but the underlying mechanisms are largely unclear. Using culture-independent Illumina MiSeq sequencing of the bacterial 16S rRNA gene amplicons, we show that bacterial diversity in the intestine of Caenorhabditis elegans, the free-living nematode, is distinct from that in soil. Of these bacteria, Bacillus subtilis is the most prominent species in the worm gut. We demonstrate that B. subtilis confers worm resistance to infection by pathogenic bacteria, such as Pseudomonas aeruginosa, Salmonella enterica, and Enterococcus faecalis, by producing nitric oxide (NO). Deletion of the nos gene, which encodes an NO synthase, reduces the protective effect. NO promotes innate immune responses to P. aeruginosa PA14 by activating a conserved p38 mitogen protein kinase (MAPK) in C. elegans. Our work provides an example of antagonism of commensal bacteria against pathogens and illustrates the importance of commensal bacteria in host immunity. PMID- 26854224 TI - RNF20 Links Histone H2B Ubiquitylation with Inflammation and Inflammation Associated Cancer. AB - Factors linking inflammation and cancer are of great interest. We now report that the chromatin-targeting E3 ubiquitin ligase RNF20/RNF40, driving histone H2B monoubiquitylation (H2Bub1), modulates inflammation and inflammation-associated cancer in mice and humans. Downregulation of RNF20 and H2Bub1 favors recruitment of p65-containing nuclear factor kappaB (NF-kappaB) dimers over repressive p50 homodimers and decreases the heterochromatin mark H3K9me3 on a subset of NF kappaB target genes to augment their transcription. Concordantly, RNF20(+/-) mice are predisposed to acute and chronic colonic inflammation and inflammation associated colorectal cancer, with excessive myeloid-derived suppressor cells (MDSCs) that may quench antitumoral T cell activity. Notably, colons of human ulcerative colitis patients, as well as colorectal tumors, reveal downregulation of RNF20/RNF40 and H2Bub1 in both epithelium and stroma, supporting the clinical relevance of our tissue culture and mouse model findings. PMID- 26854226 TI - Ligand-Induced Receptor-like Kinase Complex Regulates Floral Organ Abscission in Arabidopsis. AB - Abscission is a developmental process that enables plants to shed unwanted organs. In Arabidopsis, the floral organ abscission is regulated by a signaling pathway consisting of the peptide ligand IDA, the receptor-like kinases (RLKs) HAE and HSL2, and a downstream MAP kinase (MAPK) cascade. However, little is known about the molecular link between ligand-receptor pairs and intracellular signaling. Here, we report that the SERK family RLKs function redundantly in regulating floral organ abscission downstream of IDA and upstream of the MAPK cascade. IDA induces heterodimerization of HAE/HSL2 and SERKs, which transphosphorylate each other. The SERK3 residues mediating its interaction with the immune receptor FLS2 and the brassinosteroid receptor BRI1 are also required for IDA-induced HAE/HSL2-SERK3 interaction, suggesting SERKs serve as co receptors of HAE/HSL2 in perceiving IDA. Thus, our study reveals the signaling activation mechanism in floral organ abscission by IDA-induced HAE/HSL2-SERK complex formation accompanied by transphosphorylation. PMID- 26854227 TI - PRMT7 Preserves Satellite Cell Regenerative Capacity. AB - Regeneration of skeletal muscle requires the continued presence of quiescent muscle stem cells (satellite cells), which become activated in response to injury. Here, we report that whole-body protein arginine methyltransferase PRMT7( /-) adult mice and mice conditionally lacking PRMT7 in satellite cells using Pax7 CreERT2 both display a significant reduction in satellite cell function, leading to defects in regenerative capacity upon muscle injury. We show that PRMT7 is preferentially expressed in activated satellite cells and, interestingly, PRMT7 deficient satellite cells undergo cell-cycle arrest and premature cellular senescence. These defects underlie poor satellite cell stem cell capacity to regenerate muscle and self-renew after injury. PRMT7-deficient satellite cells express elevated levels of the CDK inhibitor p21CIP1 and low levels of its repressor, DNMT3b. Restoration of DNMT3b in PRMT7-deficient cells rescues PRMT7 mediated senescence. Our findings define PRMT7 as a regulator of the DNMT3b/p21 axis required to maintain muscle stem cell regenerative capacity. PMID- 26854229 TI - Regulation of Memory Formation by the Transcription Factor XBP1. AB - Contextual memory formation relies on the induction of new genes in the hippocampus. A polymorphism in the promoter of the transcription factor XBP1 was identified as a risk factor for Alzheimer's disease and bipolar disorders. XBP1 is a major regulator of the unfolded protein response (UPR), mediating adaptation to endoplasmic reticulum (ER) stress. Using a phenotypic screen, we uncovered an unexpected function of XBP1 in cognition and behavior. Mice lacking XBP1 in the nervous system showed specific impairment of contextual memory formation and long term potentiation (LTP), whereas neuronal XBP1s overexpression improved performance in memory tasks. Gene expression analysis revealed that XBP1 regulates a group of memory-related genes, highlighting brain-derived neurotrophic factor (BDNF), a key component in memory consolidation. Overexpression of BDNF in the hippocampus reversed the XBP1-deficient phenotype. Our study revealed an unanticipated function of XBP1 in cognitive processes that is apparently unrelated to its role in ER stress. PMID- 26854228 TI - 5-Hydroxymethylcytosine Marks Sites of DNA Damage and Promotes Genome Stability. AB - 5-hydroxymethylcytosine (5hmC) is a DNA base created during active DNA demethylation by the recently discovered TET enzymes. 5hmC has essential roles in gene expression and differentiation. Here, we demonstrate that 5hmC also localizes to sites of DNA damage and repair. 5hmC accumulates at damage foci induced by aphidicolin and microirradiation and colocalizes with major DNA damage response proteins 53BP1 and gammaH2AX, revealing 5hmC as an epigenetic marker of DNA damage. Deficiency for the TET enzymes eliminates damage-induced 5hmC accumulation and elicits chromosome segregation defects in response to replication stress. Our results indicate that the TET enzymes and 5hmC play essential roles in ensuring genome integrity. PMID- 26854230 TI - Work Done by Titin Protein Folding Assists Muscle Contraction. AB - Current theories of muscle contraction propose that the power stroke of a myosin motor is the sole source of mechanical energy driving the sliding filaments of a contracting muscle. These models exclude titin, the largest protein in the human body, which determines the passive elasticity of muscles. Here, we show that stepwise unfolding/folding of titin immunoglobulin (Ig) domains occurs in the elastic I band region of intact myofibrils at physiological sarcomere lengths and forces of 6-8 pN. We use single-molecule techniques to demonstrate that unfolded titin Ig domains undergo a spontaneous stepwise folding contraction at forces below 10 pN, delivering up to 105 zJ of additional contractile energy, which is larger than the mechanical energy delivered by the power stroke of a myosin motor. Thus, it appears inescapable that folding of titin Ig domains is an important, but as yet unrecognized, contributor to the force generated by a contracting muscle. PMID- 26854231 TI - RAB-5- and DYNAMIN-1-Mediated Endocytosis of EFF-1 Fusogen Controls Cell-Cell Fusion. AB - Cell-cell fusion plays essential roles during fertilization and organogenesis. Previous studies in C. elegans led to the identification of the eukaryotic fusion protein (EFF-1 fusogen), which has structural homology to class II viral fusogens. Transcriptional repression of EFF-1 ensures correct fusion fates, and overexpression of EFF-1 results in embryonic lethality. EFF-1 must be expressed on the surface of both fusing cells; however, little is known regarding how cells regulate EFF-1 surface exposure. Here, we report that EFF-1 is actively removed from the plasma membrane of epidermal cells by dynamin- and RAB-5-dependent endocytosis and accumulates in early endosomes. EFF-1 was transiently localized to apical domains of fusion-competent cells. Effective cell-cell fusion occurred only between pairs of cell membranes in which EFF-1 localized. Downregulation of dynamin or RAB-5 caused EFF-1 mislocalization to all apical membrane domains and excessive fusion. Thus, internalization of EFF-1 is a safety mechanism preventing excessive cell fusion. PMID- 26854232 TI - ARHGAP12 Functions as a Developmental Brake on Excitatory Synapse Function. AB - The molecular mechanisms that promote excitatory synapse development have been extensively studied. However, the molecular events preventing precocious excitatory synapse development so that synapses form at the correct time and place are less well understood. Here, we report the functional characterization of ARHGAP12, a previously uncharacterized Rho GTPase-activating protein (RhoGAP) in the brain. ARHGAP12 is specifically expressed in the CA1 region of the hippocampus, where it localizes to the postsynaptic compartment of excitatory synapses. ARHGAP12 negatively controls spine size via its RhoGAP activity and promotes, by interacting with CIP4, postsynaptic AMPA receptor endocytosis. Arhgap12 knockdown results in precocious maturation of excitatory synapses, as indicated by a reduction in the proportion of silent synapses. Collectively, our data show that ARHGAP12 is a synaptic RhoGAP that regulates excitatory synaptic structure and function during development. PMID- 26854233 TI - Zebrafish Embryonic Lipidomic Analysis Reveals that the Yolk Cell Is Metabolically Active in Processing Lipid. AB - The role of lipids in providing energy and structural cellular components during vertebrate development is poorly understood. To elucidate these roles further, we visualized lipid deposition and examined expression of key lipid-regulating genes during zebrafish embryogenesis. We also conducted a semiquantitative analysis of lipidomic composition using liquid chromatography (LC)-mass spectrometry. Finally, we analyzed processing of boron-dipyrromethene (BODIPY) lipid analogs injected into the yolk using thin layer chromatography. Our data reveal that the most abundant lipids in the embryo are cholesterol, phosphatidylcholine, and triglyceride. Moreover, we demonstrate that lipids are processed within the yolk prior to mobilization to the embryonic body. Our data identify a metabolically active yolk and body resulting in a dynamic lipid composition. This provides a foundation for studying lipid biology during normal or pharmacologically compromised embryogenesis. PMID- 26854234 TI - ATRIP Deacetylation by SIRT2 Drives ATR Checkpoint Activation by Promoting Binding to RPA-ssDNA. AB - The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase checkpoint pathway maintains genome integrity; however, the role of the sirtuin 2 (SIRT2) acetylome in regulating this pathway is not clear. We found that deacetylation of ATR-interacting protein (ATRIP), a regulatory partner of ATR, by SIRT2 potentiates the ATR checkpoint. SIRT2 interacts with and deacetylates ATRIP at lysine 32 (K32) in response to replication stress. SIRT2 deacetylation of ATRIP at K32 drives ATR autophosphorylation and signaling and facilitates DNA replication fork progression and recovery of stalled replication forks. K32 deacetylation by SIRT2 further promotes ATRIP accumulation to DNA damage sites and binding to replication protein A-coated single-stranded DNA (RPA-ssDNA). Collectively, these results support a model in which ATRIP deacetylation by SIRT2 promotes ATR-ATRIP binding to RPA-ssDNA to drive ATR activation and thus facilitate recovery from replication stress, outlining a mechanism by which the ATR checkpoint is regulated by SIRT2 through deacetylation. PMID- 26854235 TI - KRAS Engages AGO2 to Enhance Cellular Transformation. AB - Oncogenic mutations in RAS provide a compelling yet intractable therapeutic target. Using co-immunoprecipitation mass spectrometry, we uncovered an interaction between RAS and Argonaute 2 (AGO2). Endogenously, RAS and AGO2 co sediment and co-localize in the endoplasmic reticulum. The AGO2 N-terminal domain directly binds the Switch II region of KRAS, agnostic of nucleotide (GDP/GTP) binding. Functionally, AGO2 knockdown attenuates cell proliferation in mutant KRAS-dependent cells and AGO2 overexpression enhances KRAS(G12V)-mediated transformation. Using AGO2-/- cells, we demonstrate that the RAS-AGO2 interaction is required for maximal mutant KRAS expression and cellular transformation. Mechanistically, oncogenic KRAS attenuates AGO2-mediated gene silencing. Overall, the functional interaction with AGO2 extends KRAS function beyond its canonical role in signaling. PMID- 26854237 TI - Post-translational Regulation of Cas9 during G1 Enhances Homology-Directed Repair. AB - CRISPR/Cas9 induces DNA double-strand breaks that are repaired by cell-autonomous repair pathways, namely, non-homologous end-joining (NHEJ), or homology-directed repair (HDR). While HDR is absent in G1, NHEJ is active throughout the cell cycle and, thus, is largely favored over HDR. We devised a strategy to increase HDR by directly synchronizing the expression of Cas9 with cell-cycle progression. Fusion of Cas9 to the N-terminal region of human Geminin converted this gene-editing protein into a substrate for the E3 ubiquitin ligase complex APC/Cdh1, resulting in a cell-cycle-tailored expression with low levels in G1 but high expression in S/G2/M. Importantly, Cas9-hGem(1/110) increased the rate of HDR by up to 87% compared to wild-type Cas9. Future developments may enable high-resolution expression of genome engineering proteins, which might increase HDR rates further, and may contribute to a better understanding of DNA repair pathways due to spatiotemporal control of DNA damage induction. PMID- 26854238 TI - Selenium deficiency induced damages and altered expressions of metalloproteinases and their inhibitors (MMP1/3, TIMP1/3) in the kidneys of growing rats. AB - Selenium is an essential trace element for the maintenance of structures and functions of kidney. To evaluate the effects of low selenium on the kidneys of growing rats, newborn rats were fed with selenium deficient and normal diets respectively for 109 days. As a result, rats fed with low selenium diets resulted in a decline in the body weight and the concentration of selenium in the kidney, especially the male rats from the low selenium groups. Moreover, the ultrastructure of glomerulus and tubules were damaged in low selenium group: the glomeruli were observed with hyperplasia of mesangial cells, fusion of podocyte foot processes and thickening of basement membrane; and the tubules were observed with vacuolar degenerated epithelial cells, increased edema fluid or protein solution between cells, microvilli edema, increased cell gaps and decreased cell links. Furthermore, the pathological changes in selenium deficient group included the increase of fibers around renal hilum aorta and in the renal collecting duct, and shed of cells in the proximal convoluted tubules. In addition, up-regulated expressions of matrix metalloproteinases (MMP1/3) and down-regulated expressions of their inhibitors (TIMP1/3) at the mRNA and protein levels were also appeared to be relevant to low selenium. The results suggested that low selenium in diet may cause low selenium concentration in the kidney of growing rat and lead to damages of the ultrastructure and extracellular matrix (ECM) of kidney. PMID- 26854236 TI - Gastric Helicobacter pylori Infection Affects Local and Distant Microbial Populations and Host Responses. AB - Helicobacter pylori is a late-in-life human pathogen with potential early-life benefits. Although H. pylori is disappearing from the human population, little is known about the influence of H. pylori on the host's microbiota and immunity. Studying the interactions of H. pylori with murine hosts over 6 months, we found stable colonization accompanied by gastric histologic and antibody responses. Analysis of gastric and pulmonary tissues revealed increased expression of multiple immune response genes, conserved across mice and over time in the stomach and more transiently in the lungs. Moreover, H. pylori infection led to significantly different population structures in both the gastric and intestinal microbiota. These studies indicate that H. pylori influences the microbiota and host immune responses not only locally in the stomach, but distantly as well, affecting important target organs. PMID- 26854239 TI - Selenium and its relationship with selenoprotein P and glutathione peroxidase in children and adolescents with Hashimoto's thyroiditis and hypothyroidism. AB - The essential trace element selenium (Se) is required for thyroid hormone synthesis and metabolism. Selenoproteins contain selenocysteine and are responsible for biological functions of selenium. Glutathione peroxidase (GPx) is one of the major selenoproteins which protects the thyroid cells from oxidative damage. Selenoprotein P (SePP) is considered as the plasma selenium transporter to tissues. The aim of this study was to evaluate serum Se and SePP levels, and GPx activity in erythrocytes of children and adolescents with treated Hashimoto's thyroiditis, hypothyroidism, and normal subjects. Blood samples were collected from 32 patients with Hashimoto's thyroiditis, 20 with hypothyroidism, and 25 matched normal subjects. All the patients were under treatment with levothyroxine and at the time of analysis all of the thyroid function tests were normal. GPx enzyme activity was measured by spectrophotometry at 340 nm. Serum selenium levels were measured by high-resolution continuum source graphite furnace atomic absorption. SePP, TPOAb (anti-thyroid peroxidase antibody), and TgAb (anti thyroglobulin antibody) were determined by ELISA kits. T4, T3, T3 uptake and TSH were also measured. Neither GPx activity nor SePP levels were significantly different in patients with Hashimoto's thyroiditis or hypothyroidism compared to normal subjects. Although GPx and SePP were both lower in patients with hypothyroidism compared to those with Hashimoto's thyroiditis and normal subjects but the difference was not significant. Serum Se levels also did not differ significantly in patients and normal subjects. We did not find any correlation between GPx or SePP with TPOAb or TgAb but SePP was significantly correlated with Se. Results show that in patients with Hashimoto's thyroiditis or hypothyroidism who have been under treatment with levothyroxine and have normal thyroid function tests, the GPx, SePP and Se levels are not significantly different. PMID- 26854240 TI - Operationally defined species characterization and bioaccessibility evaluation of cobalt, copper and selenium in Cape gooseberry (Physalis Peruviana L.) by SEC-ICP MS. AB - Physalis peruviana could attract great interest because of its nutritional and industrial properties. It is an excellent source of vitamins, minerals, essential fatty acids and carotenoids. Physalis Peruviana is also known to have a positive impact on human health. Unfortunately, still little is known about trace elements present in Physalis Peruviana and their forms available for the human body. Thus, the aim of this study was to estimate bioaccessibility and characterization of species of cobalt, copper and selenium in Physalis Peruviana fruits. Total and extractable contents of elements were determined by mass spectrometer with inductively coupled plasma (ICP MS). In order to separate the different types of metal complexes Physalis peruviana fruits were treated with the following solvents: Tris-HCl (pH 7.4), sodium dodecyl sulfate (SDS) (pH 7.4) and ammonium acetate (pH 5.5). The best efficiency of extraction of: cobalt was obtained for ammonium acetate (56%) and Tris-HCl (60%); for copper was obtained for SDS (66%), for selenium the best extraction efficiency was obtained after extraction with SDS (48%). To obtain information about bioaccessibility of investigated elements, enzymatic extraction based on in vitro simulation of gastric (pepsin) and intestinal (pancreatin) digestion was performed. For copper and selenium the simulation of gastric digestion leads to the extraction yield above 90%, while both steps of digestion method were necessary to obtain satisfactory extraction yield in the case of cobalt. Size exclusion chromatography (SEC) coupled to on line ICP MS detection was used to investigate collected metal species. The main fraction of metal compounds was found in the 17 kDa region. Cobalt and copper create complexes mostly with compounds extracted by means of ammonium acetate and SDS, respectively. Cobalt, copper and selenium were found to be highly bioaccessible from Physalis Peruviana. Investigation of available standards of cobalt and selenium allows confirming the presence of vitamin B12 and probably selenomethionine in the fraction bioaccessible by human body (obtained during enzymatic extraction). It should be noted that the presence of small seleno compounds in Cape gooseberry was performed for the first time. The results show that the combination of SEC and ICP MS could provide a simple method for separating of soluble element species. PMID- 26854241 TI - Biological production of silver nanoparticles by soil isolated bacteria and preliminary study of their cytotoxicity and cutaneous wound healing efficiency in rat. AB - Biosynthesis of AgNPs by 37 different bacterial soil isolates was done and confirmed through visible spectrophotometry. Fifteen isolates were identified and two of them with the highest ability of AgNPs production were used for Transmission Electron Microscopy (TEM) and X-ray diffraction (XRD) tests. MTT assay for both of the obtained AgNPs was run and after determination their IC50s, two different toxic and nontoxic doses of each AgNPs solution were chosen for wound healing assay. Forty eight rats were divided into 6 groups; two were the controls, two were administrated by the toxic and two were administrated by the nontoxic doses of AgNPs produced by Bacillus cereus and Escherichia fergusonii. Administration of the nontoxic doses of AgNPs had better wound healing effect than both of the toxic ones. The control groups had less wound healing properties. In conclusion, biologically produced AgNPs in their nontoxic doses accelerated the collagen formation and the epithelization and decelerated the angiogenesis and duration of completion the epithelization. PMID- 26854243 TI - Improving accuracy of normal serum copper. PMID- 26854242 TI - Iodine in autism spectrum disorders. AB - OBJECTIVE: The aim of our study was to assess the iodine status of Polish boys with severe autism compared to their healthy peers and evaluate the relationship between urinary iodine, thyroid hormones, body mass index and Autism Spectrum Disorder (ASD) symptomatology. SUBJECTS AND METHODS: Tests were performed in 40 boys with ASD and 40 healthy boys, aged 2-17 from the same geographic region in Poland. Urinary iodine (UI), free triiodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH), BMI, and individual symptoms measured by the Childhood Autism Rating Scale (CARS) were correlated. Validated ion chromatography method with pulsed amperometric detection was applied for the determination of urinary iodine after optimized alkaline digestion in a closed system assisted with microwaves. RESULTS: 19 out of 40 children with ASD had mild to moderate iodine deficiency. Statistically significant lower levels of UI, fT3 and fT4 and higher levels of TSH were found in the autistic group when compared with the control group. Concentration of iodine in urine was negatively associated with clinician's general impression for children between 11 and 17 years. Emotional response, adaptation to environmental change, near receptor responsiveness, verbal communication, activity level, and intellectual functioning are more associated with UI than other symptoms listed in CARS. CONCLUSION: The severity of certain symptoms in autism is associated with iodine status in maturing boys. Thyroid hormones were within normal reference ranges in both groups while urinary iodine was significantly lower in autistic boys suggesting that further studies into the nonhormonal role of iodine in autism are required. PMID- 26854244 TI - The effect of copper nanoparticles supplementation on freshwater prawn Macrobrachium rosenbergii post larvae. AB - The present study was performed to assess the effects of dietary supplementation of copper nanoparticles (Cu-NPs) on growth, biochemical constituents, digestive enzyme activities, antioxidant, metabolic enzyme levels, and non specific immune response of the freshwater prawn, Macrobrachium rosenbergii post larvae (PL). The Cu-NPs (200 nm) were synthesized by facile and environmental friendly hydrothermal method. Cu-NPs were supplemented at 0, 10, 20, 40, 60, and 80 mg kg( 1) with the basal diets. These Cu-NPs supplemented diets were fed to M. rosenbergii PL for 90 days. Results showed significant (P<0.05) improvements were observed in survival, growth, digestive enzyme activities, concentrations of biochemical constituents and total and differential haemocytes count of prawns fed with 20 mg Cu-NPs kg(-1) supplemented feed. Prawns fed with 40-80 mg Cu-NPs kg(-1) supplemented feed showed negative performance. Activity of antioxidants and metabolic enzymes in the muscle and hepatopancreas of prawns showed no significant alterations (P>0.05) prawns fed with up to 20 mg Cu-NPs kg(-1) supplemented feeds. Whereas, prawns fed with 40-80 mg Cu-NPs kg(-1) supplemented feed showed significant (P<0.05) elevations in antioxidant and metabolic enzymes activities. Hence, 40-80 mg Cu-NPs kg(-1) diets may have toxic effect to M. rosenbergii. Hence, present study suggests that 20 mg Cu-NPs kg(-1) can be supplemented for regulating better survival, growth and immune response of M. rosenbergii PL. PMID- 26854245 TI - Metal bioaccumulation in consumed marine bivalves in Southeast Brazilian coast. AB - This work aimed to investigate metal bioaccumulation by mussels (Perna perna) and Lion's Scallop (Nodipecten nodosus) farmed in tropical bays, in order to estimate spatial and temporal variation in the exposure to these elements, as well as human health risk. The concentration of each measured element was considered for this evaluation, using maximum residue level (MRL) in foods established by the Brazilian (ANVISA), American (USFDA) and European Communities (EC) legislations. Values for estimated daily ingestion (EDI) were determined for metals intake through mussel and scallop consumption. These estimates were compared with the reference value of (PTDI) proposed by World Health Organization (WHO). Trace elements concentration was measured on ninety mussels P. perna (tissue) and ninety Lion's Scallop N. nodosus (muscle and gonad) reared in four different tropical areas of the Southeast Brazilian coast, between 2009 and 2010. Zinc (Zn), Iron (Fe), Copper (Cu), Manganese (Mn), Chrome (Cr), Nickel (Ni), Cadmium (Cd) and Lead (Pb) concentrations were measured by flame atomic absorption spectrometry after acid mineralization. Cd and Mn were more efficiently bioaccumulated by scallops than mussels and the opposite was found for Fe, Cu and Ni. Guanabara Bay and Sepetiba Bay were considered the most impacted between ecosystems studied. Higher Cd values in Arraial do Cabo in the other sites studied were associated with upwelling that occurs in the region. Consumption of both species cannot be considered safe, because the Cu and Cr concentrations, in accordance with the limits established by the Brazilian Agency (ANVISA). On the other hand, any EDI value exceeded the corresponding value of the PTDI, proposed by World Health Organization (WHO). PMID- 26854246 TI - Effects of selenium supplementation on glucose homeostasis and free androgen index in women with polycystic ovary syndrome: A randomized, double blinded, placebo controlled clinical trial. AB - BACKGROUND/OBJECTIVES: Insulin resistance (IR) is a main pathophysiologic feature in polycystic ovary syndrome (PCOS) patients which is triggered by elevated oxidative stress in these patients. Selenium, an essential micronutrient, is a major constituent of antioxidant enzymes such as glutathione peroxidase. Recently, decreased plasma selenium concentrations were reported in PCOS patients. So, the present study was carried out in order to assess whether selenium consumption can improve the metabolic response to insulin and reduce the insulin resistance in these women. SUBJECTS/METHODS: A total of 53 PCOS patients (diagnosed by Rotterdam criteria), 18-42 years old, participated in this randomized, double-blind and placebo controlled trial for 12 weeks (selenium, n=26; placebo, n=27). The effects of daily administration of 200 MUg selenium or placebo on serum glucose, total testosterone (tT), sex hormone binding globulin (SHBG) and free androgen index (FAI) in fasting state were evaluated. RESULTS: At the end of the study, insulin resistance was significantly increased in selenium recipients when compared with the placebo group (2.05 +/- 0.39 when compared with 1.81 +/- 0.25, p=0.017). Also, selenium supplementation resulted in marginally significant increase (p=0.056) in insulin level when compared with the placebo group. There were no statistically significant changes in other study endpoints, when comparing the two groups. CONCLUSION: This study showed that selenium supplementation in PCOS patients may worsen insulin resistance in them. Until the results of larger studies become available, indiscriminate consumption of selenium supplements in PCOS patients will warrant caution. PMID- 26854247 TI - Iron-induced oxidative stress activates AKT and ERK1/2 and decreases Dyrk1B and PRMT1 in neuroblastoma SH-SY5Y cells. AB - Iron is essential for proper neuronal functioning; however, excessive accumulation of brain iron is reported in Parkinson's, Alzheimer's, Huntington's diseases and amyotrophic lateral sclerosis. This indicates that dysregulated iron homeostasis is involved in the pathogenesis of these diseases. To determinate the effect of iron on oxidative stress and on cell survival pathways, such as AKT, ERK1/2 and DyrK1B, neuroblastoma SH-SY5Y cells were exposed to different concentration of FeCl2 (iron). We found that iron induced cell death in SH-SY5Y cells in a concentration-dependent manner. Detection of iNOS and 3-nitrotyrosine confirms the presence of increased nitrogen species. Furthermore, we found a decrease of catalase and protein arginine methyl-transferase 1 (PRMT1). Interestingly, iron increased the activity of ERK and AKT and reduced DyrK1B. Moreover, after FeCl2 treatment, the transcription factors c-Jun and pSmad1/5 were activated. These results indicate that the presence of high levels of iron increase the vulnerability of neurons to oxidative stress. PMID- 26854248 TI - Investigation of thermostable metalloproteins in Perna perna mussels from differentially contaminated areas in Southeastern Brazil by bioanalytical techniques. AB - Metallomic studies regarding environmental contamination by metals are of value in elucidating metal uptake, trafficking, accumulation and metabolism in biological systems. Many proven bioindicator species, such as bivalves, have not yet, however, been well-characterized regarding their metalloprotein expression in response to environmental contaminants. In this context, the aim of the present study was to investigate metalloprotein expressions in the thermostable protein fraction of muscle tissue and digestive glands from mussels (Perna perna) from three differentially metal-contaminated sites in Southeastern Brazil in comparison with a reference site. The thermostable protein fractions were analyzed by SDS-PAGE and SEC-HPLC-ICP-MS. Metal content was also determined in both the crude and the purified extracts. Several inter-organ differences were observed, which is to be expected, while inter-site differences regarding thermostable protein content were also verified, indicating accumulation of these elements in muscle tissue and digestive glands and disruption of homeostasis of essential elements, with detoxification attempts by metal-bound proteins, since all metalloproteins present in both matrices eluted bound to at least one non essential metal. These results are also noteworthy with regard to the adopted reference site, that also seems to be contaminated by toxic metals. PMID- 26854249 TI - The importance of pyridoxine for the impact of the dietary selenium sources on redox balance, embryo development, and reproductive performance in gilts. AB - This study aimed to determine the effects of dietary pyridoxine and selenium (Se) on embryo development, reproductive performance and redox system in gilts. Eighty four gilts were fed one of five diets: CONT) basal diet; MSeB60) CONT+0.3mg/kg of Na-selenite; MSeB610) diet 2+10mg/kg of HCl-pyridoxine; OSeB60) CONT+0.3mg/kg of Se-enriched yeast; and OSeB610) diet 4+10mg/kg of HCl-pyridoxine. Blood samples were collected for long-term (each estrus and slaughter) and peri-estrus (fourth estrus d -4 to d +3) profiles. At slaughter (gestation d 30), organs and embryos were collected. For long-term and peri-estrus profiles, Se level and source affected (P<0.01) blood Se concentration whereas B6 level increased (P<0.01) erythrocyte pyridoxal-5-phosphate concentration. A B6 level (P<0.05) effect was observed on long-term plasma Se-dependent glutathione peroxidase (Se-GPX) activity whereas peri-estrus Se-GPX was minimum on d -1 (P<0.01). Selenium level increased sows' organs and embryo Se concentration (P<0.01). Selenium source tended to enhance embryo Se content (P=0.06). Within-litter embryo Se content was increased by B6 level (P<0.01). Selenium level tended to affect Se-GPX and total GPX activities in organs mitochondria (P=0.09 and 0.07, respectively). Selenium source affected kidney ATP synthesis (P=0.05). In conclusion, B6 level affected the Se-GPX activity on a long-term basis, whereas the basal level of Se was adequate during the peri-estrus period. Embryo quality was not improved by dietary Se, and B6 impaired within-litter homogeneity. PMID- 26854250 TI - Mean platelet volume and cardiovascular risk factors. PMID- 26854251 TI - Increased risk of concurrent gastroesophageal reflux disease among patients with Sjogren's syndrome: A nationwide population-based study. AB - BACKGROUND: Little data is available on the risk of gastroesophageal reflux disease in patients diagnosed with Sjogren's syndrome. METHODS: We identified 4650 Sjogren's syndrome patients between 2000 and 2011 from the National Health Insurance Research Database. Each Sjogren's syndrome patient was matched to 4 controls based on age, sex, and index year, and all subjects were followed up from the index date to December 31, 2011. Cox proportional hazards regression model was used to estimate the risk of gastroesophageal reflux disease. RESULTS: The risk of gastroesophageal reflux disease for Sjogren's syndrome patients was 2.41-fold greater than that for the comparison cohort after adjusting for age, sex, and comorbidities. In age stratified analyses, the youngest Sjogren's syndrome cohort (age: 20-44years old) had the highest risk (HR=3.02; 95% CI=2.48 3.69) and the lowest risk at age >=65years (HR=1.95; 95% CI=1.61-2.36). Regardless of in subjects with and without comorbidity, Sjogren's syndrome patients had a higher risk than the controls. Sjogren's syndrome subjects with ischemic heart disease, hyperlipidemia and renal disease had the highest risk for gastroesophageal reflux disease compared with the comparison cohort without those diseases (HR=7.67; 95% CI=5.32-11.1). CONCLUSION: Patients with Sjogren's syndrome have a significantly greater risk of developing subsequent gastroesophageal reflux disease than the general population. PMID- 26854252 TI - Naming the Precursors of Conjunctival Melanoma. PMID- 26854253 TI - Expression of phospholipase A2 receptor in primary cultured podocytes derived from dog kidneys. AB - Phospholipase A2 receptor (PLA2R) expressed in human podocytes has been highlighted as a causative autoantigen of human idiopathic membranous nephropathy. However, its expression was found to be minimal or absent in murine and rat podocytes. In this study, immunofluorescence revealed the expression of PLA2R in the glomerular podocytes in the kidney tissue sections of dogs. We then attempted to culture canine podocytes and investigate the expression of PLA2R in these cells. Glomeruli were isolated from dog kidneys and cultured to obtain podocytes using nylon mesh-based isolation method as followed for isolating rat podocytes. The cultured cells expressed PLA2R mRNA and protein in addition to other podocyte markers (synaptopodin, podocin and nephrin). These results indicate that the canine podocytes express PLA2R. PMID- 26854254 TI - A two-step binding mechanism for the self-binding peptide recognition of target domains. AB - Self-binding peptides (SBPs) represent a novel biomolecular phenomenon spanning between folding and binding, where a short peptide segment within a monomeric protein fulfills biological functions by dynamically binding to/unbinding from its target domain in the same monomer. Here, we were able to quantitatively reconstruct the complete structural dynamics picture of binding of free SBPs to their target domains for five representative SBP systems by carrying out the state-of-the-art molecular dynamics (MD) simulations. In the picture, a two-step binding mechanism for SBP-domain recognition and association was proposed, which includes a fast, nonspecific diffusive phase and a slow, specific organizational phase. The electrostatic interactions and desolvation effects play a predominant role in the first phase that leads to the formation of a metastable encounter complex, while conformational rearrangement is observed in the second phase to optimize the exquisite network of nonbonded chemical forces such as hydrogen bonds and salt bridges across the complex interface. From an energetic point of view, a funnel-shape enthalpy landscape steers these SBPs towards their native bound state and thus facilitates the binding process. However, the binding exhibits typical enthalpy-entropy compensation due to the high flexibility of peptides that results in a relatively low affinity for SBP-domain binding and forces the SBP systems to rapidly switch between the bound and unbound states. In addition, slight conformational changes in the target domain and/or in the polypeptide linker between the domain and peptide can significantly affect the energetic properties and dynamic behavior of the fine-tuned binding process of SBP-domain recognition. PMID- 26854255 TI - Frailty and famine: Patterns of mortality and physiological stress among victims of famine in medieval London. AB - OBJECTIVES: Famine can be defined as a shortage of foodstuffs that instigates widespread excess mortality due to starvation, infectious disease, and social disruption. Like other causes of catastrophic mortality, famine has the potential to be selective. This study examines how famines in medieval London were selective with respect to previous stress, age, and sex. METHODS: This study compares famine burials to nonfamine (attritional) burials from the St Mary Spital cemetery, London (c. 1120-1540 AD). We evaluate the associations between age, sex, and skeletal stress indicators [cribra orbitalia, linear enamel hypoplasia (LEH), and periosteal lesions] using hierarchical log-linear analysis. Additionally, sex is modeled as a covariate affecting the Gompertz hazard of mortality. RESULTS: Significant associations exist between famine burials and LEH and between attritional burials and periosteal lesions, independent of age or sex. Sex did not significantly affect risk of mortality in the 12th-13th centuries. However, males interred in attritional burials c. 1400-1539 AD faced a lower risk of mortality compared to females. DISCUSSION: The LEH results suggest that early exposure to stressors increased frailty in the context of famine. The periosteal lesion results suggest that individuals were more likely to survive stressors and thus form these lesions under nonfamine conditions. Hazard analysis suggests that a cultural or biological transformation during this period affected sex differences in mortality. Possible causes include the selective mortality during the Black Death, which might have influenced risks of mortality among survivors, or unequal distribution of improvements in standards of living after the epidemic. Am J Phys Anthropol 160:272-283, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26854256 TI - A large variety of clinical features and concomitant disorders in celiac disease A cohort study in the Netherlands. AB - BACKGROUND AND AIMS: Celiac disease (CeD) is a gluten triggered, immune-mediated disease of the small intestine. Few clinical cohort descriptions are available, despite the diverse clinical picture. This study provides an overview of a large Dutch CeD cohort focusing on presenting symptoms, co-occurrence of immune mediated diseases (IMD) and malignancies. METHODS: We performed a retrospective study in a Dutch university and a non-university medical hospital and included only biopsy proven (>=Marsh type 2 classification) CeD patients. RESULTS: 412 patients were included, selected from 9468 small-bowel biopsy pathology reports and financial codes. Classical symptoms were present in approximately one third of the cohort (diarrhea (37.4%), fatigue (35.0%), weight loss (31.6%), abdominal pain (33.3%)). Atypical symptoms as constipation (10.4%) and reflux (12.4%) were reported as well. 11.7% was diagnosed without reported symptoms. In 25.2% concomitant IMD occurred (most prevalent: type 1 diabetes mellitus (4.9%), microscopic colitis (4.9%), immune mediated-thyroid disease (4.1%)). CeD patients with a concomitant IMD were diagnosed at a significantly higher age compared to those without (P=0.002). Malignancies occurred in 53 cases (12.9%), including eight Enteropathy Associated T-cell Lymphomas. CONCLUSION: This is the first study describing a CeD cohort in such detail in the Netherlands and highlights the clinical heterogeneity and importance of screening for concomitant diseases in CeD. PMID- 26854257 TI - Short term colectomy rate and mortality for severe ulcerative colitis in the last 40 years. Has something changed? AB - BACKGROUND: About 20% of ulcerative colitis patients will experience a severe attack during the course of the disease. Intensive treatment, early surgery and, more recently, "rescue therapies" improved prognosis. AIMS: To evaluate in hospital colectomy and mortality rates for severe ulcerative colitis over 40 years in two referral centres. METHODS: All in-patients with severe ulcerative colitis from 1976 to 2010 were considered. 159 patients were assigned to 4 cohorts: cohort 1 n=34 (1976-1980); cohort 2 n=29 (1986-1990); cohort 3 n=45 (1996-2000); cohort 4 n=51 (2006-2010). RESULTS: The colectomy rate was 64.7%, 62.0%, 44.4% and 9.8%, respectively, in the four cohorts (p<0.0001). The mortality rate decreased from 8.8% in cohort 1, to 0 in cohort 4 (p=0.04). Infliximab was used only in cohort 4 (17 patients). CONCLUSIONS: A significant reduction of colectomy and mortality rates in severe ulcerative colitis was observed in the last 40 years. Better management of patients, reduced attitude to operate severe ulcerative colitis, as well as the use of Infliximab in the last cohort, all could have contributed to the improved outcome. PMID- 26854258 TI - Resistance to thrombomodulin is associated with de novo portal vein thrombosis and low survival in patients with cirrhosis. AB - BACKGROUND & AIMS: Portal vein thrombosis (PVT) is frequently observed in cirrhosis and may be a clinically important complication. In vitro assays for endogenous thrombin potential (ETP) demonstrated that in cirrhosis plasma has intrinsic resistance to the anticoagulant action of thrombomodulin (TM-R). This study retrospectively explores the association of TM-R with de novo PVT and its clinical impact on cirrhosis. METHODS: Fifty-three patients with cirrhosis were tested for ETP-ratio with/without thrombomodulin. Clinical, endoscopic variables, presence/absence of PVT by Doppler-US and/or CT examination were collected at baseline and up to 4 years from baseline. The de novo PVT was the primary clinical end-point. Portal hypertension (PHT)-related complications and transplantation free survival were secondary end-points. ETP-ratio higher than the 95 degrees percentile of the distribution in 173 healthy controls defined TM R. RESULTS: During 48 months of follow-up, 11 patients developed de novo PVT, with preference for the 36 patients with TM-R after adjusting for Child-Pugh class (HR: 8.354; 90%CI:1.475 - 47.305; P = 0.009). Seventeen patients experienced PHT-related complications, 23 either died or underwent liver transplantation. PHT complications and transplantation free survival were associated with TM-R, but were independently predicted by Child-Pugh class, only. Same results were obtained by considering the MELD score. CONCLUSIONS: Owing to PVT results from the pro-coagulant imbalance occurring in patients with advanced cirrhosis, TM-R might serve as a predictor and could possibly be a biological mediator of adverse outcome in patients with advanced cirrhosis. PMID- 26854259 TI - Thirty percent of abstracts presented at dental conferences are published in full: a systematic review. AB - OBJECTIVES: To review the publication fate of abstracts presented at dental conferences and investigate the association between full publication proportion (FPP) and abstract characteristics, conference characteristics, and methodological quality of primary studies. STUDY DESIGN AND SETTING: PubMed, EMBASE, and Google Scholar were searched up to November 2014 for studies that reported at least one FPP of abstracts presented at dental conferences, with a follow-up length of no less than 48 months. RESULTS: Sixteen studies involving 10,365 abstracts presented at 52 conferences were included. The pooled FPP was 29.62% (95% confidence interval: 22.90%, 36.81%) for all presented abstracts and 51.97% (95% confidence interval: 43.19%, 60.70%) for randomized controlled trial abstracts. Abstract characteristics significantly associated with higher FPP included reporting of statistical analysis (P < 0.001), oral presentation (P < 0.001), basic science research (P = 0.047), and reporting of financial support (P = 0.009). Abstracts with positive (P = 0.29) or statistically significant results (P = 0.33) were not published more often than negative or nonsignificant results, respectively. In multivariable meta-regression analysis, conferences held in Asia (P < 0.001) and at a continental rather than national level (P < 0.001) were significantly associated with higher FPP. CONCLUSIONS: Less than one-third of abstracts presented at dental conferences were published in full more than 4 years after conference presentation. PMID- 26854261 TI - Time-resolved fluctuation during the photochemical reaction of a photoreceptor protein: phototropin1LOV2-linker. AB - Although the relationship between structural fluctuations and reactions is important for elucidating reaction mechanisms, experimental data describing such fluctuations of reaction intermediates are sparse. In order to investigate structural fluctuations during a protein reaction, the compressibilities of intermediate species after photoexcitation of a phot1LOV2-linker, which is a typical LOV domain protein with the C-terminal linker including the J-alpha helix and used recently for optogenetics, were measured in the time-domain by the transient grating and transient lens methods with a high pressure optical cell. The yield of covalent bond formation between the chromophore and a Cys residue (S state formation) relative to that at 0.1 MPa decreased very slightly with increasing pressure. The fraction of the reactive species that yields the T state (linker-unfolded state) decreased almost proportionally with pressure (0.1-200 MPa) to about 65%. Interestingly, the volume change associated with the reaction was much more pressure sensitive. By combining these data, the compressibility changes for the short lived intermediate (S state) and the final product (T state) formation were determined. The compressibility of the S state was found to increase compared with the dark (D) state, and the compressibility decreased during the transition from the S state to the T state. The compressibility change is discussed in terms of cavities inside the protein. By comparing the crystal structures of the phot1LOV2-linker at dark and light states, we concluded that the cavity volumes between the LOV domain and the linker domain increase in the S state, which explains the enhanced compressibility. PMID- 26854263 TI - Enzymatic activatable self-assembled peptide nanowire for targeted therapy and fluorescence imaging of tumors. AB - We developed novel activatable probe using self-assembled peptide nanowires with low affinity and toxicity to tumor cells in the absence of matrix metalloproteinase that showed activated high affinity and toxicity and provided a highly selective and efficient platform for targeted therapy and tumor imaging. PMID- 26854260 TI - The occurrence of Simpson's paradox if site-level effect was ignored in the TREAT Asia HIV Observational Database. AB - OBJECTIVES: In multisite human immunodeficiency virus (HIV) observational cohorts, clustering of observations often occurs within sites. Ignoring clustering may lead to "Simpson's paradox" (SP) where the trend observed in the aggregated data is reversed when the groups are separated. This study aimed to investigate the SP in an Asian HIV cohort and the effects of site-level adjustment through various Cox regression models. STUDY DESIGN AND SETTING: Survival time from combination antiretroviral therapy (cART) initiation was analyzed using four Cox models: (1) no site adjustment; (2) site as a fixed effect; (3) stratification through site; and (4) shared frailty on site. RESULTS: A total of 6,454 patients were included from 23 sites in Asia. SP was evident in the year of cART initiation variable. Model (1) shows the hazard ratio (HR) for years 2010-2014 was higher than the HR for 2006-2009, compared to 2003-2005 (HR = 0.68 vs. 0.61). Models (2)-(4) consistently implied greater improvement in survival for those who initiated in 2010-2014 than 2006-2009 contrasting findings from model (1). The effects of other significant covariates on survival were similar across four models. CONCLUSIONS: Ignoring site can lead to SP causing reversal of treatment effects. Greater emphasis should be made to include site in survival models when possible. PMID- 26854264 TI - Large negative thermal expansion in non-perovskite lead-free ferroelectric Sn2P2S6. AB - Functional materials showing both negative thermal expansion (NTE) and physical performance, such as ferroelectricity and magnetism, have been extensively explored in the past decade. However, among ferroelectrics a remarkable NTE was only found in perovskite-type PbTiO3-based compounds. In this work, a large NTE of -4.7 * 10(-5) K(-1) is obtained in the non-perovskite lead-free ferroelectric Sn2P2S6 from 243 K to TC (338 K). Structure refinements and first-principle calculations reveal the effects of the Sn(ii) 5s-S 3p interaction on spontaneous polarization and its correlation with NTE. Then the mechanism of spontaneous volume ferroelectrostriction (SVFS) is verified and it could well elucidate the nature of NTE in ferroelectric Sn2P2S6. This is the first case to demonstrate the unusual NTE behavior by SVFS in a non-perovskite lead-free ferroelectric material. PMID- 26854262 TI - The importance of the gastrorenal axis in the control of body sodium homeostasis. AB - NEW FINDINGS: What is the topic of this review? Sensing the amount of ingested sodium is one mechanism by which sodium balance is regulated. This review describes the role of gastrin in the cross-talk between the stomach and the kidney following the ingestion of sodium. What advances does it highlight? Neural mechanisms and several gut hormones, including cholecystokinin and uroguanylin, have been suggested to mediate the natriuresis after an oral sodium load. It is proposed that gastrin produced by G-cells via its receptor, cholecystokinin B receptor, interacts with renal D1 -like dopamine receptors to increase renal sodium excretion. Hypertension develops with chronically increased sodium intake when sodium that accumulates in the body can no longer be sequestered, extracellular fluid volume is expanded, and compensatory neural, hormonal and pressure-natriuresis mechanisms fail. Sensing the amount of ingested sodium, by the stomach, is one mechanism by which sodium balance is regulated. The natriuresis following the ingestion of a certain amount of sodium may be due to an enterokine, gastrin, secreted by G-cells in the stomach and duodenum and released into the circulation. Circulating gastrin levels are 10- to 20-fold higher than those for cholecystokinin. Of all the gut hormones circulating in the plasma, gastrin is the one that is reabsorbed to the greatest extent by renal tubules. Gastrin, via its receptor, the cholecystokinin type B receptor (CCKBR), is natriuretic in mammals, including humans, by inhibition of renal sodium transport. Germline deletion of gastrin (Gast) or Cckbr gene in mice causes salt sensitive hypertension. Selective silencing of Gast in the stomach and duodenum impairs the ability to excrete an oral sodium load and also increases blood pressure. Thus, the gastrorenal axis, mediated by gastrin, can complement pronatriuretic hormones, such as dopamine, to increase sodium excretion after an oral sodium load. These studies in mice may be translatable to humans because the chromosomal loci of CCKBR and GAST are linked to human essential hypertension. Understanding the role of genes in the regulation of renal function and blood pressure may lead to the tailoring of antihypertensive treatment based on genetic make-up. PMID- 26854265 TI - Antineoplastic agents and thrombotic microangiopathy. AB - Thrombotic microangiopathy is an uncommon but reported adverse effect of a variety of antineoplastic drugs, including chemotherapy agents such as mitomycin C and gemcitabine, and newer targeted agents such as the vascular endothelial growth factor inhibitors. We present a review of thrombotic microangiopathy associated with antineoplastic agents and its implications in current cancer therapy. PMID- 26854266 TI - Safety of anticoagulation in thrombocytopenic patients with hematologic malignancies: A case series. AB - The incidence of venous thromboembolism is greater among cancer patients than the general patient population, with recurrence rates also much higher in patients with cancer diagnoses. Patients with hematologic malignancies often experience prolonged periods of thrombocytopenia throughout their disease course, making therapeutic anticoagulation a challenge. We describe 13 cases of patients with hematologic malignancies that were therapeutically anticoagulated with either low molecular-weight heparin or unfractionated heparin during periods of severe thrombocytopenia (platelet counts < 50 * 109/uL). Patients were included if they had a diagnosis code for a hematologic malignancy and venous thromboembolism between 1 January 2010 and 31 December 2012. The diagnosis of venous thromboembolism included both deep vein thrombosis and pulmonary embolism. There was one bleeding event, World Health Organization grade 2, that was documented in a patient receiving enoxaparin dosed twice daily, resulting in an overall bleeding rate of 7.7% in this case series. All 13 patients were administered platelet transfusions during the periods of severe thrombocytopenia. While each patient case must have the risks and benefits weighed individually, we observed that anticoagulation for the treatment of venous thromboembolism during periods of thrombocytopenia may be considered in patients with hematologic malignancies. PMID- 26854267 TI - Pharmacists' roles in oncology pharmacy services: Results of a global survey. AB - Background Oncology pharmacists are capable of providing medication therapy management (MTM) because of their level of training, practice experiences, and responsibilities. Very little data exist about their current practice, including changing roles in the multidisciplinary team, overall impact, and effects in the education of patients and healthcare professionals. Methods A 70-item survey about oncology pharmacists' activities in oral chemotherapy programs, MTM, and collaborative practice agreements (CPAs) was deployed using a web survey tool (Qualtrics, Provo, UT, USA), targeting pharmacist members of American College of Clinical Pharmacy (ACCP) Hematology/Oncology Practice and Research Network (PRN). The objective of this study was to determine oncology pharmacists' activities in areas of oral chemotherapy programs, MTM, and CPAs. A cross-sectional survey was distributed to the ACCP Hematology/Oncology PRN membership. Investigational Review Board approval was obtained. Results Of the 795 members who were sent the survey, 81 members (10%) responded; 33 respondents (47%) are involved with an oral chemotherapy program; with 42% measuring outcomes of programs. Only six pharmacists (19%) have published or presented their data. A total of 28 (35%) respondents provide MTM services, with almost half (43%) of these MTM services being dictated by CPAs. A small fraction of these pharmacists (21.4%) reported conducting quality assurance evaluations of their MTM services and three pharmacists (10.7%) reported publishing their results. Those pharmacists practicing under CPAs ( n = 28) were surveyed as to activities included in their CPA. The most common activities included adjusting medication, ordering, interpreting, and monitoring lab tests, developing therapeutic plans and educating patients. Reimbursement for providing these services was uncommon: MTM (4%), oral chemotherapy program (6%), and CPA services (11%). Reported obstacles to reimbursement included lack of understanding, administrative assistance, or time with setting up reimbursement models within the institution. Conclusion Many oncology pharmacists are participating in oral chemotherapy programs, MTM, and/or CPAs and perceived barriers were identified. Increased efforts should be directed toward prospectively reporting and assessing the impact these services have on patient care. PMID- 26854268 TI - Evaluation of nasal mucociliary transport rate according to nasal septum deviation type. AB - BACKGROUND: Nasal septum deviation (NSD) may affect mucociliary activity (MCA) to varying degrees, depending upon the severity of the deviation. We used rhinoscintigraphy to determine the impact of the various NSD types on MCA. METHODS: A recent classification describing 6 different forms of NSD was used to standardize the study. Forty-eight subjects were enrolled. Eight patients for each form of NSD were accrued for further study. Rhinoscintigraphy was performed using technetium 99m macroaggregated albumin ((99m) Tc-MAA) before and 3 months after surgery. Nasal mucociliary transport rate (NMTR), the half-time of (99m) Tc MAA activity, and clearance rate over a 20-minute period were compared between groups. RESULTS: Preoperative NMTR and clearance rates were significantly lower and half-time was significantly longer in types 4 and 6 than in the other groups. Although the postoperative NMTR and clearance rates increased compared with preoperative values in all groups, the increase was significant only in types 2, 4, and 6. The postoperative half-time increased significantly compared with the preoperative values in types 2, 4, and 6. The postoperative rhinoscintigraphy evaluation revealed no significant differences among groups in NMTR, half-time, or clearance rate. CONCLUSION: NSD types 4 and 6 had lower preoperative NMTR and clearance rates and a longer half-time compared with the other groups. However, the postoperative values of these parameters were not significantly different among groups. Our results indicate that NSD types 4 and 6 had the greatest impact on MCA, suggesting that these patients may receive the maximum benefit from septoplasty. PMID- 26854269 TI - Polymer-Based Ruthenium(II) Polypyridyl Chromophores on TiO2 for Solar Energy Conversion. AB - A polychromophoric light-harvesting assembly featuring a polystyrene (PS) backbone with ionic carboxylate-functionalized Ru(II) polypyridyl complexes as pendant groups (PS-Ru-A) was synthesized and successfully anchored onto mesoporous structured TiO2 films (TiO2 //PS-Ru-A). Studies of the resulting TiO2 //PS-Ru-A films carried out by transmission electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) confirmed that the ionic carboxylated Ru(II) complexes from PS-Ru-A led to the surface immobilization on the TiO2 film. Monochromatic light photocurrent spectroscopy (IPCE) and white light (AM1.5G) current-voltage studies of dye-sensitized solar cells using the TiO2 //PS-Ru-A photoanode give rise to modest photocurrent and white light efficiency (24 % peak IPCE and 0.33 % PCE, respectively). The photostability of surface-bound TiO2 //PS-Ru-A films was tested and compared to a monomeric Ru(II) complex (TiO2 //Ru-A), showing an enhancement of ~14 % in the photostability of PS-Ru-A. Transient absorption measurements reveal that electron injection from surface-bound pendants occurs on the picosecond time scale, similar to TiO2 //Ru-A, while time-resolved emission measurements reveal delayed electron injection occurring in TiO2 //PS-Ru-A on the nanosecond time scale, underscoring energy transport from unbound to surface-bound complexes. Additionally, charge recombination is delayed in PS-Ru-A, pointing towards intra assembly hole transport to complexes away from the surface. Molecular dynamics simulations of PS-Ru-A in fluid solution indicate that a majority of the pendant Ru(II) complexes lie within 10-20 A of each other, facilitating efficient energy- and charge transport among the pendant complexes. PMID- 26854270 TI - The Case of the Woman Who Did Never Dare to Fly: Headache Attributed to Imbalance Between Intrasinusal and External Air Pressure. AB - BACKGROUND: A new form of headache, Headache attributed to aeroplane travel (AH), has been recognized within the International Classification of Headache Disorders 3 beta (ICHD-3beta). In 8 out of 85 AH cases we identified the coexistence of a headache with identical features of AH, but appearing during the rapid descent by car from a high mountain. Pain began shortly after the rapid descent from a medium altitude of 1920 m above sea level, the maximum peak of intensity developing within a few minutes. All of the patients reported the disappearance of pain within 20 minutes of the rapid descent. CASE: We recently observed a 36 year-old woman who experienced recurrent headache attacks that were constantly triggered by rapid descent from high altitude by car. Negatively shaped by this experience, the patient never dared to fly. CONCLUSION: Headache attacks sharing the same features and occurring in three distinct conditions of pressure variations (aeroplane travel, rapid altitude mountain descent, snorkelling, or scuba diving) have already been reported, although the last two only anecdotally. If confirmed by further case series, they could be gathered together in a unique heading: Headache attributed to imbalance between intrasinusal and external air pressure within the 10th chapter: Headache attributed to disorders of the homoeostasis. PMID- 26854271 TI - Mapping changes in cortical activity during sleep in the first 4 years of life. AB - A coherent body of evidence supports the notion that sleep is a local and use dependent process. Significant changes in brain morphology and function occur in the first years of life, revealing a postero-anterior trajectory of cortical maturation. On this basis, a recent study demonstrated that regional cortical maturation between early childhood and late adolescence is reflected in regional changes of sleep slow wave activity (SWA) during non-rapid eye movement (NREM) sleep. Our hypothesis is that changes of electroencephalogram (EEG) rhythms during sleep from birth to childhood are also mirrored by parallel regional changes in the EEG rhythms of sleep according to the assumption of a postero anterior gradient in cortical maturation. We studied all-night EEG of 39 healthy, full-term, infants and children aged between 0 and 48 months, evaluating regional differences in NREM sleep. We confirmed the strictly local nature of sleep with frequency-specific regional differences. Specifically, we found a general shift of maxima of the upper alpha activity from occipital to prefrontal regions, expressed mainly by the ~11 Hz frequency. This shift corresponds to a postero anterior trajectory of the so-called 'slow spindles'. The theta and alpha EEG activity of the frontal cortex exhibits a clear, positive, correlation with age. We conclude that specific local differences during NREM sleep, parallel cortical maturation also in the first 4 years of life. PMID- 26854272 TI - Perioperative management of novel oral anticoagulants in skin surgery: a national survey. PMID- 26854273 TI - Factors affecting media coverage of species rediscoveries. PMID- 26854276 TI - Effects of different lipid sources on intake, digestibility and purine derivatives in hair lambs. AB - An experiment was conducted to evaluate the effects of different lipid sources on the nutrient intake, digestibility and purine derivative excretion of lambs. Thirty-five 60-day-old, male, non-castrated Santa Ines lambs with an initial average body weight (BW) of 13.00 +/- 1.80 kg were used in a randomized complete block design with seven blocks and five treatments. The experimental treatments consisted of a control diet without supplemental lipids and four test diets with different lipid supplements, selected according to the degree of ruminal protection from hydrogenation: supplementation, being supplementation with whole cottonseed (WC), supplementation with cashew nut meal (CNM), supplementation with both cottonseed and cashew nut meal (WC-CNM) and supplementation with calcium salts of long-chain fatty acids (Ca-LCFA). The lambs were slaughtered after reaching 28 kg average BW for each treatment. The ether extract intake (EEI) was higher (p < 0.01) for the lipid supplemented compared to control diet lambs. Supplementation with WC decreased the digestibility of dry matter (DM), organic matter (OM), neutral detergent fibre (NDF) and total carbohydrate (TC) (p < 0.01), whereas supplementation with CNM, WC-CNM and Ca-LCFA reduced non-fibrous carbohydrate (NFC) digestibility (p < 0.01). The ether extract (EE) digestibility coefficient was higher with CNM, followed by Ca-LCFA and WC, when compared to WC CNM and control diets. Nitrogen balance (NB) was not influenced (p > 0.05) by the different lipid sources. A lower purine derivative (PD) excretion and thus lower microbial protein supply (MPS) was observed for animals supplemented with Ca-LCFA (p < 0.01) compared to the WC-CNM and control diets. In conclusion, WC, CNM and WC-CNM supplementation did not have negative effects on MPS, although negative effects have been observed on nutrient digestibility. PMID- 26854275 TI - Neural FFA3 activation inversely regulates anion secretion evoked by nicotinic ACh receptor activation in rat proximal colon. AB - KEY POINTS: Luminal short-chain fatty acids (SCFAs) influence gut physiological function via SCFA receptors and transporters. The contribution of an SCFA receptor, free fatty acid receptor (FFA)3, to the enteric nervous system is unknown. FFA3 is expressed in enteric cholinergic neurons. Activation of neural FFA3 suppresses Cl(-) secretion induced by nicotinic ACh receptor activation via a Gi/o pathway. Neural FFA3 may have an anti-secretory function by modulating cholinergic neural reflexes in the enteric nervous system. ABSTRACT: The proximal colonic mucosa is constantly exposed to high concentrations of microbially produced short-chain fatty acids (SCFAs). Although luminal SCFAs evoke electrogenic anion secretion and smooth muscle contractility via neural and non neural cholinergic pathways in the colon, the involvement of the SCFA receptor free fatty acid receptor (FFA)3, one of the free fatty acid receptor family members, has not been clarified. We investigated the contribution of FFA3 to cholinergic-mediated secretory responses in rat proximal colon. FFA3 was immunolocalized to enteroendocrine cells and to the enteric neural plexuses. Most FFA3-immunoreactive nerve fibres and nerve endings were cholinergic, colocalized with protein gene product (PGP)9.5, the vesicular ACh transporter, and the high affinity choline transporter CHT1. In Ussing chambered mucosa-submucosa preparations (including the submucosal plexus) of rat proximal colon, carbachol (CCh)-induced Cl(-) secretion was decreased by TTX, hexamethonium, and the serosal FFA3 agonists acetate or propionate, although not by an inactive analogue 3-chloropropionate. Serosal application of a selective FFA3 agonist (N-[2 methylphenyl]-[4-furan-3-yl]-2-methyl-5-oxo-1,4,5,6,7,8-hexahydro-quinoline-3 carboxamide; MQC) dose-dependently suppressed the response to CCh but not to forskolin, with an IC50 of 13 MUm. Pretreatment with MQC inhibited nicotine evoked but not bethanechol-evoked secretion. The inhibitory effect of MQC was reversed by pretreatment with pertussis toxin, indicating that FFA3 acts via the Gi/o pathway. Luminal propionate induced Cl(-) secretion via the cholinergic pathway, which was reduced by MQC, as well as by TTX, hexamethonium or removal of the submucosal plexus. These results suggest that the SCFA-FFA3 pathway has a novel anti-secretory function in that it inhibits cholinergic neural reflexes in the enteric nervous system. PMID- 26854277 TI - The Pharmacokinetics of Potassium in Humans Is Unusual. AB - Potassium is critical for maintaining cellular tonicity, propagation of nerve impulses, contraction of cardiac, skeletal, and smooth muscles, and normal renal function. The focus of this review is on the pharmacokinetics of potassium, K(+) , after administration of liquid and solid formulations of potassium chloride, KCl, to healthy subjects. Potassium can be considered an endogenous and exogenous compound. The amounts of endogenous K(+) are kept constant by balancing intake and loss of exogenous K(+) . Food and ingestion of KCl-containing medicines are sources for exogenous K(+) . In the pharmacokinetic context exogenous K(+) from KCl-containing medicines, K(+) exo,dose , is of primary interest. The distinction between the different K(+) entities is critical for obtaining unbiased estimates of the kinetic parameters for K(+) exo,dose . A literature search using prespecified acceptance criteria was performed. Publications were selected that reported plasma and urine data of K(+) exo,dose directly or provided information allowing their determination. Additional criteria applied included that the studies used a randomized design and controlled for the important covariates. Most of the selected publications reported urinary excretion data. Only 2 publications also reported plasma concentrations. The excursions of the plasma concentrations of K(+) exo,dose were considered too small to be of use by most investigators. The aggregate results indicate that urinary recovery data have the potential for providing reliable estimates for bioavailability and bioequivalence of K(+) exo,dose with KCl-containing formulations. Absorption efficiency, peak rates, and corresponding times of K(+) exo,dose with liquid formulations are fairly consistent among studies. The mean absorption efficiency of K(+) exo,dose with solid and liquid formulations of KCl ranges between 70% and 90%. The absorption rate of liquid formulations is rapid, whereas the solid formulations show extended release characteristics. The time-averaged renal clearance of K(+) exo,dose is about 200 mL/min during daytime and significantly smaller around midnight. Circadian rhythm and delayed homeostatic control of potassium make the pharmacokinetics of K(+) exo,dose time dependent. The impact of these endogenous controls makes the pharmacokinetics of K(+) exo,dose unusual. PMID- 26854278 TI - Increasing prevalence of membranous nephropathy in patients with primary glomerular diseases: A cross-sectional study in China. AB - AIM: Primary glomerular disease (PGD) remains the most common renal disease in China. A limited number of single centre studies show that the frequency of membranous nephropathy (MN) has increased; however, IgA nephropathy (IgAN) is still the most common PGD. To the best of our knowledge, there has been no multi centre study in China that has explored the changes in PGD spectrum. To further investigate the changes in renal histopathological spectrum, we performed the cross-sectional study. METHOD: From June 2010 to May 2015, 5935 patients from 37 hospitals in Shandong Province were involved in this retrospective study. The study was divided into five periods according to 1-year intervals. The patients were divided into four age groups (<=18 years, 19-44 years, 45-59 years and >=60 years). RESULT: Among the 5935 qualified specimens, 4855 (81.8%) were diagnosed with PGD. MN (43.3%) became the most common PGD instead of IgA (34.1%) (P < 0.001). The frequency of MN was increased from 30.7% in period 1 to 53.5% in period 5 (P < 0.001). The prevalence of MN tended to increase in every age section. IgA was the main cause of PGD in periods 1 and 2; however, its proportion decreased significantly from 41.8% in period 2 to 25.2% in period 5 (P < 0.001). CONCLUSION: Primary glomerular disease remains the most common renal disease in our study. For the first time, this cross-sectional study suggests that MN, in place of IgAN, has grown to be the first leading pathological type of PGD. PMID- 26854279 TI - Contact Force-Guided Deep Engagement with a Steerable Sheath in the Distal Great Cardiac Vein: A Case Report. AB - Ablation of ventricular tachycardia originating from the great cardiac vein involves the difficult step of deep engagement with an ablation catheter. The catheter and a steerable sheath (MobiCath, Biosense Webster, Diamond Bar, CA, USA) were advanced alternately only when the contact force vector was parallel to the coronary venous system. Deep engagement with a steerable sheath ensured a powerful backup force during ablation. PMID- 26854280 TI - Identifying the Minimal Enzymes for Unusual Carbon-Sulfur Bond Formation in Thienodolin Biosynthesis. AB - Thienodolin (THN) features a tricyclic indole-S-hetero scaffold that encompasses two unique carbon-sulfur bonds. Although its biosynthetic gene cluster has been recently identified in Streptomyces albogriseolus, the essential enzymes for the formation of C-S bonds have been relatively unexplored. Here, we isolated and characterized a new biosynthetic gene cluster from Streptomyces sp. FXJ1.172. Heterologous expression, systematic gene inactivation, and in vitro biochemical characterization enable us to determine the minimum set of genes for THN synthesis, and an aminotransferase (ThnJ) for catalyzing the downstream conversion of tryptophan chlorination. In addition, we evaluated (and mainly excluded) a previously assumed pivotal intermediate by feeding experiments. With these results, we narrowed down four enzymes (ThnC-F) that are responsible for the two unprecedented C-S bond formations. Our study provides a solid basis for further unraveling of the unique C-S mechanisms. PMID- 26854281 TI - Social predictors of less frequent dental attendance over time among older people: population-averaged and person-specific estimates. AB - OBJECTIVES: Longitudinal studies considering social disparities in the utilization of dental services are scarce. Repeated measures should be accounted for by the use of appropriate statistical methods. The purpose of this study was first to describe the patterns of less frequent dental attendance (less than once a year) over time from the age of 65-70 in Norwegian and Swedish 1942 cohorts. Second, this study estimated the influence of predisposing, enabling and need related social predictors using marginal model with robust variance estimators and random intercept model, RIM, to account for the clustered structure of the repeated observations. Third, the study aimed to compare the estimates of associations between social predictors and less frequent dental attendance derived from marginal and random intercept models. METHODS: In 2007 and 2012, all residents born in 1942 in selected counties of Norway and Sweden were invited to participate in a questionnaire survey. In Norway, the response rate was 58.0% (n = 4211) in 2007 and 54.5% (n = 3733) in 2012 with a follow-up rate of 70%. The corresponding figures in Sweden were 73.1% (n = 6078) and 72.2% (n = 5697), with a follow-up rate of 80%. Marginal and random intercept models were fitted for population-averaged and person-specific estimates. Design effects were calculated by comparing the results from ordinary logistic regression analyses and the marginal model with robust variance estimators. The proportion of the total variation due to differences between persons was reported using the intraclass correlation coefficient (ICC). RESULTS: Less frequent dental attendance declined from 14.5% to 12.2% in Norway and from 13.6% to 12.9% in Sweden. According to marginal and random intercept models, time-invariant (gender, country of birth, education) and time-variant social predictors (working status, social network, marital status, smoking and perceived health) contributed to less frequent dental attendance. A likelihood ratio test confirmed that adjustment for clustered observations was appropriate. The ICC was 0.90 in Norway and 0.85 in Sweden. CONCLUSIONS: The prevalence of less frequent dental attendance was low and dropped by increasing age from 65 to 70 years. Both at population and at person specific levels, being advantaged on social aspects protects against less frequent dental attendance after 65 years of age in the Norwegian and Swedish cohorts investigated. PMID- 26854282 TI - Determination of azithromycin residue in pork using a molecularly imprinted monolithic microcolumn coupled to liquid chromatography with tandem mass spectrometry. AB - Using spiramycin as a dummy template, a molecularly imprinted polymer monolithic micro-column with high selection to azithromycin was prepared in a micropipette tip. The imprinting factor of the monolithic micro-column prepared was approximately 2.67 and the morphological structure of the polymers was characterized by scanning electron microscopy. A simple, sensitive, and reproducible method based on the imprinted monolithic micro-column coupled to liquid chromatography with tandem mass spectrometry was developed for determining the residues of azithromycin in pork. Pork samples were extracted with acetonitrile, cleaned up under the optimal monolithic micro-column conditions, and analyzed using liquid chromatography with tandem mass spectrometry in the multiple reaction monitoring mode. The assay exhibited a linear dynamic range of 0.50-50 MUg/L with the correlation coefficient (r(2) ) above 0.99. In the three spiking levels of 0.50, 1.0, and 10 MUg/kg, the average recoveries of azithromycin from pork samples were between 85.8 and 96.5% with a relative standard deviation below 10%. The limit of detection and limit of quantitation were 0.03 and 0.1 MUg/kg, respectively. PMID- 26854283 TI - Gatekeepers as Care Providers: The Care Work of Patient-centered Medical Home Clerical Staff. AB - International implementation of the patient-centered medical home (PCMH) model for delivering primary care has dramatically increased in the last decade. A majority of research on PCMH's impact has emphasized the care provided by clinically trained staff. In this article, we report our ethnographic analysis of data collected from Department of Veterans Affairs staff implementing PACT, the VA version of PCMH. Teams were trained to use within-team delegation, largely accomplished through attention to clinical licensure, to differentiate staff in providing efficient, patient-centered care. In doing so, PACT may reinforce a clinically defined culture of care that countermands PCMH ideals. Such competing rubrics for care are brought into relief through a focus on the care work performed by clerks. Ethnographic analysis identifies clerks' care as a kind of emotional dirty work, signaling important areas for future anthropological study of the relationships among patient-centered care, stigma, and clinical authority. PMID- 26854284 TI - Iridium(I) N-Heterocyclic Carbene (NHC)/Phosphine Catalysts for Mild and Chemoselective Hydrogenation Processes. AB - The directed chemoselective hydrogenation of olefins has been established by using iridium(I) catalysts, which feature a tuned NHC/phosphine ligand combination. This selective reduction process has been demonstrated in a wide array of solvents, including more environmentally acceptable media, also allowing further refinement of hydrogenation selectivity. PMID- 26854285 TI - Lipid emulsion for intoxication by local anaesthetic: sunken sink? PMID- 26854287 TI - Wagemans, J. (Ed.). The Oxford Handbook of Perceptual Organization. PMID- 26854286 TI - Effects of Vertical Direction and Aperture Size on the Perception of Visual Acceleration. AB - It is not well understood whether the distance over which moving stimuli are visible affects our sensitivity to the presence of acceleration or our ability to track such stimuli. It is also uncertain whether our experience with gravity creates anisotropies in how we detect vertical acceleration and deceleration. To address these questions, we varied the vertical extent of the aperture through which we presented vertically accelerating and decelerating random dot arrays. We hypothesized that observers would better detect and pursue accelerating and decelerating stimuli that extend over larger than smaller distances. In Experiment 1, we tested the effects of vertical direction and aperture size on acceleration and deceleration detection accuracy. Results indicated that detection is better for downward motion and for large apertures, but there is no difference between vertical acceleration and deceleration detection. A control experiment revealed that our manipulation of vertical aperture size affects the ability to track vertical motion. Smooth pursuit is better (i.e., with higher peak velocities) for large apertures than for small apertures. Our findings suggest that the ability to detect vertical acceleration and deceleration varies as a function of the direction and vertical extent over which an observer can track the moving stimulus. PMID- 26854288 TI - Extra-abdominal removal of placenta during cesarean section: a prospective randomized controlled trial of a novel technique. AB - AIM: To evaluate intraoperative and early postoperative outcomes of a novel placenta delivery technique; extra-abdominal removal vs. intra-abdominal removal of the placenta during cesarean section (CS). METHODS: A total of 210 women delivering by CS at term in a tertiary university hospital between March 2014 and January 2015 were randomized to extra-abdominal removal vs. intra-abdominal removal of the placenta. The women were randomly allocated to the extra- (group 1) or intra-abdominal removal group (group 2) according to random sampling method, where women with even and odd numbers were allocated to intra- and extra abdominal groups, respectively. The amount of intra-abdominal hemorrhagic fluid accumulation, the duration of operation and estimated blood loss during operation were the primary outcomes. The secondary outcomes included the mean difference between pre- and post-operative hemoglobin and hematocrit levels, the mean postoperative pain score, any additional need of analgesia, postoperative bowel function, postoperative endometritis and wound infections. RESULTS: The amount of aspirated hemorrhagic fluid was significantly higher in the intra-abdominal group compared to the extra-abdominal group (34.6+/-22.2 mL vs. 9.4+/-4.8 mL, P<0.001). Mean duration of the operation, intraoperative blood loss, postoperative requirement of additional analgesia, postoperative pain scores, postoperative endometritis or wound infection, and length of hospital stay were not significantly different between the intra- and extra-abdominal placental removal groups. CONCLUSION: By extra-abdominal removal of the placenta, the accumulation of bloody fluid in the abdominal cavity is significantly less compared to the intra-abdominal removal method, which, in turn, provides avoidance of excessive mounted-gauze use, intra-abdominal manipulations, or iatrogenic trauma. PMID- 26854289 TI - Neutrophils in cystic fibrosis. AB - Cystic fibrosis (CF) lung disease is characterized by chronic infection and inflammation. Among inflammatory cells, neutrophils represent the major cell population accumulating in the airways of CF patients. While neutrophils provide the first defensive cellular shield against bacterial and fungal pathogens, in chronic disease conditions such as CF these short-lived immune cells release their toxic granule contents that cause tissue remodeling and irreversible structural damage to the host. A variety of human and murine studies have analyzed neutrophils and their products in the context of CF, yet their precise functional role and therapeutic potential remain controversial and incompletely understood. Here, we summarize the current evidence in this field to shed light on the complex and multi-faceted role of neutrophils in CF lung disease. PMID- 26854290 TI - Characterization of the nuclear import mechanisms of HSV-1 UL31. AB - As an important protein, UL31 has been demonstrated to play multiple roles in herpes simplex virus 1 (HSV-1) replication. Previous studies showed that UL31 predominantly locates in the nucleus in chemical fixed cells and live cells, however, the determining mechanisms for its nuclear translocation is not clear. In the present study, by utilizing live cells fluorescent microscopy and co immunoprecipitation assays, the nuclear import of UL31 was characterized to be dependent on Ran-, importin alpha1- and transportin-1-mediated pathway. Therefore, these results will promote the understanding of UL31-mediated biological functions in HSV-1 infection cycle. PMID- 26854291 TI - Contrasting effects of cardiac glycosides on cisplatin- and etoposide-induced cell death. AB - Cardiac glycosides (CGs) or cardiotonic steroids, which constitute a group of naturally occurring compounds with a steroid-like structure, can act on Na+/K+ ATPase as a receptor and activate intracellular signaling messengers leading to a variety of cellular responses. Epidemiological studies have revealed that CGs, used for the treatment of cardiac disorders, may also be beneficial as anti cancer agents. CGs, acting in combination with other chemotherapeutic agents, may significantly alter their efficiency in relation to cancer cell elimination, causing both sensitization and an increase in cancer cell death, and in some cases resistance to chemotherapy. Here we show the ability of CGs to modulate apoptotic response to conventionally used anti-cancer drugs. In combination with etoposide, CGs digoxin may enhance cytotoxic potential, thereby allowing the chemotherapeutic dose to be decreased and minimizing toxicity and adverse reactions. Mechanisms behind this event are discussed. PMID- 26854292 TI - HMM-Fisher: identifying differential methylation using a hidden Markov model and Fisher's exact test. AB - DNA methylation is an epigenetic event that plays an important role in regulating gene expression. It is important to study DNA methylation, especially differential methylation patterns between two groups of samples (e.g. patients vs. normal individuals). With next generation sequencing technologies, it is now possible to identify differential methylation patterns by considering methylation at the single CG site level in an entire genome. However, it is challenging to analyze large and complex NGS data. In order to address this difficult question, we have developed a new statistical method using a hidden Markov model and Fisher's exact test (HMM-Fisher) to identify differentially methylated cytosines and regions. We first use a hidden Markov chain to model the methylation signals to infer the methylation state as Not methylated (N), Partly methylated (P), and Fully methylated (F) for each individual sample. We then use Fisher's exact test to identify differentially methylated CG sites. We show the HMM-Fisher method and compare it with commonly cited methods using both simulated data and real sequencing data. The results show that HMM-Fisher outperforms the current available methods to which we have compared. HMM-Fisher is efficient and robust in identifying heterogeneous DM regions. PMID- 26854295 TI - Donepezil: rhabdomyolysis and neuroleptic malignant syndrome. PMID- 26854296 TI - In Memoriam: Asa Harris Mosher, VMD, PhD, Diplomate ACVP, 1936-2014. PMID- 26854297 TI - Open journals that piggyback on arXiv gather momentum. PMID- 26854298 TI - The code librarian. PMID- 26854299 TI - Gianni Bonadonna: A Tribute. PMID- 26854300 TI - Gianni Bonadonna: A Personal Remembrance. PMID- 26854301 TI - Preface. PMID- 26854302 TI - Guidelines for Moderators: Roadmap to a Successful Conference. AB - The ideal moderator of a conference session does more than simply introduce the speakers to the audience: a capable facilitator can do a great deal to lead the presenters and the participants on an informative journey. This article discusses expectations of a moderator and tips that can be applied to facilitate effective and efficient sessions at professional society meetings and to optimize the satisfaction of audience members. To assist first-time moderators become adept, these guidelines are comprehensive; however, even the most experienced moderators may benefit by reviewing this article. PMID- 26854303 TI - Medical Student Usage of the American College of Radiology Appropriateness Criteria. AB - RATIONALE AND OBJECTIVES: Educating medical students on appropriate imaging utilization has been increasingly recognized as important for patient care. The American College of Radiology Appropriateness Criteria (ACR-AC) is designed to support evidence-based imaging examination selection. We sought to assess whether medical students order imaging studies independently, what resources they use for guidance, and whether they use the ACR-AC in clinical practice. A secondary aim was to determine whether increasing familiarity with the ACR-AC could impact student usage. MATERIALS AND METHODS: We surveyed third year medical students at a single institution on their imaging practices, familiarity with the ACR-AC, and preferences among available resources to guide proper examination selection. The survey was performed in person before a lecture. We also designed a brief intervention to improve familiarity with the ACR-AC and then reassessed students to determine any effect on utilization. RESULTS: The response rate for the initial survey was 103 of 109 (94%) and the response rate for the second survey was 99 of 109 (91%).Our initial survey found students initiated imaging orders independently (74 of 100, 74.8%) and consulted resources to assist in examination selection (50 of 74, 67.6%). Students expressed a preference for non-ACR-AC resources, notably Up to Date via its online mobile application.Few students (8 of 71, 11.3%) were familiar with the ACR-AC. After an intervention to increase familiarity with the ACR-AC, student awareness of the ACR-AC increased to 61 of 74 (82.4%). However, usage among those familiar with the resource remained low, 13 of 61(21.3%) versus 3 of 8 (37.5%). CONCLUSIONS: Use of the ACR-AC was low among third year medical students. After increasing students' familiarity with the ACR-AC, their usage in a clinical setting did not increase. The largest barrier to use may be the lack of a quick, easy to use online mobile application based interface. PMID- 26854304 TI - In memoriam: Leon Gordis, MD, DrPH. PMID- 26854305 TI - [Not Available]. PMID- 26854306 TI - Treating Patients as Customers--Whom Does it Help? PMID- 26854307 TI - This Business of Medicine. 1935. PMID- 26854308 TI - Rustproofing People: Beans or Beef? PMID- 26854309 TI - Money. PMID- 26854310 TI - A Comparison of Costs Between Medical and Surgical Patients in an Academic Pediatric Intensive Care Unit. AB - OBJECTIVE: To estimate the impact of patient type on costs incurred during a pediatric intensive care unit (PICU) hospitalization. PATIENTS AND METHODS: Retrospective cohort study at an academic PICU located in the United States that examined 850 patients admitted to the PICU from January 1 to December 31, 2009. Forty-eight patients were excluded due to lack of financial data. Primary service was defined by the attending physician of record. Outcome measures were total and daily pediatric intensive care costs (2009 US dollars). RESULTS: Of 802 patients in the sample, there were 361 medical and 441 surgical patients. Comparing medical to surgical patients, severity of illness as defined by Pediatric Risk of Mortality (PRISM) III scores was 4.53 vs 2.08 (P < 0.001), length of stay was 7.37 vs 5.00 days (P < 0.001), total pediatric intensive care hospital costs were $34,786 vs $30,598 (P < 0.001), and mean daily pediatric intensive care hospital costs were $3985 vs $6616 (P < 0.001). CONCLUSIONS: Medical patients had higher severity of illness and length of stay resulting in higher total pediatric intensive care costs when compared to surgical patients. Interestingly, when accounting the length of stay, surgical patients had higher daily pediatric intensive care costs despite lower severity of illness. PMID- 26854311 TI - A Novel Approach for Measuring and Communicating State Health Trends Over Time. AB - OBJECTIVE: To develop a method to assess long-term and recent progress for leading health indicators in Wisconsin. METHODS: Data from state and national sources were compiled. Baseline (10-year) trends for 20 health indicators were measured and compared to the Healthy People 2020 improvement standard of 1% per year. Additionally, current rates were assessed by comparing the most recent year of data to the expected rate had the previous 10-year baseline trend continued. Where available, health indicator trends were reported by gender, race/ethnicity, geography, and socioeconomic status. RESULTS: Wisconsin improved on 10 of the 20 indicators over the past decade, with decreasing mortality rates for all age groups. The largest improvement was a decline of 3.0% per year in deaths among ito 24 year olds. The rates of teen births and adult excessive drinking also improved by 2.5% per year and 1.4% per year, respectively. Other indicators worsened. For example, increasing rates of low birthweight (+ 0.6% per year), adults in fair or poor health (+1.6% per year), and all socioeconomic indicators worsened (high school dropouts [+0.9% per year], unemployment [+5.9% per year], children in poverty [+5.1% per year], and violent crime [+2.3% per year]). Health indicators varied substantially across subgroups within Wisconsin. For example, African Americans were twice as likely to experience low birthweight compared to other racial subgroups, and males experienced death rates higher than females across all ages. CONCLUSION: Reporting current estimates and 10-year trends of leading health indicators helps identify areas of progress and opportunities for improvement. Despite progress in reducing death rates and several other health factors, self-reported health status is worsening in Wisconsin. Worsening socioeconomic conditions and health disparities represent significant public health challenges for Wisconsin's future. PMID- 26854312 TI - Medical Student Views of the Affordable Care Act. AB - INTRODUCTION: With new insurance coverage under the Affordable Care Act (ACA) beginning in 2014 and the ever-changing practice of medicine, it is important to understand medical students' recent perspectives on health policy and reform. OBJECTIVE: This study describes the opinions, perceptions, and comprehension of the ACA and health care reform by a cross-section of medical students in Wisconsin. METHODS: A total of 578 students (35%) completed an original survey developed from previous surveys. RESULTS: Of those sampled, one-half identified as liberal or very liberal and 20% as conservative or very conservative. Respondents were split equally in their opinions of whether the United States or other nations had the highest quality care. One-half felt that faculty physicians and the media influenced their opinion of the ACA, while two-thirds felt that coursework and peers had no influence on their views. The vast majority sampled thought everyone is entitled to adequate medical care regardless of ability to pay and that physicians have a major responsibility to help reduce health care costs. A majority of liberal students and a minority of conservative students, supported the ACA. Personal and family experience as a patient influenced most liberals to support and most conservatives to oppose the ACA. One-half felt that medical school spent adequate time on health care policy education. PMID- 26854313 TI - One Wisconsin County's Experience With Fall-Related Mortality. AB - BACKGROUND: Falls in Wisconsin account for 74.1% of all injury-related deaths for persons 65 years and older. This study describes the rate, demographics, and characteristics of fall-related mortality in one Wisconsin county over an 8-year period from 2005 to 2012. METHODS: Retrospective review of 841 death investigation records of Waukesha County residents 65 years and older who died from a fall during the years 2005 to 2012. Data were collected at the Waukesha County Medical Examiner's office. RESULTS: No significant differences in individual demographics, activity, or injury characteristics (P > 0.05) in fall related deaths over an 8-year period. CONCLUSION: Fall-related mortality in Waukesha County over the past 8 years has demonstrated consistent demographics, fall, and injury characteristics. PMID- 26854314 TI - The Development of a Summary Measure to Estimate the Relative Burden of Smoking in Wisconsin Counties. AB - BACKGROUND: The rate of cigarette smoking among US adults has declined over the past 50 years. Yet smoking remains the leading cause of preventable death and marked disparities now exist in smoking rates based on education level, socioeconomic status, race/ethnicity, and geographic location. In order to target resources to reduce these disparities, a summary measure comparing the relative burden of smoking among smaller populations is needed. OBJECTIVE: To create a single summary measure that assesses the relative health burden from smoking in Wisconsin counties using age-adjusted mortality rates for smoking-attributable diseases, current adult smoking prevalence, and the current rate of mothers who smoked during pregnancy. RESULTS: Rates varied significantly between counties for smoking-attributable deaths (2-fold), adult smoking prevalence (5-fold), and smoking in pregnancy (5-fold). The summary measure of relative smoking burden was highest in rural counties and in counties with less education, higher rates of poverty, and more veterans. The ranking of a county's smoking burden was highly correlated with its overall health ranking from the County Health Rankings. DISCUSSION: The burden from smoking varied markedly across Wisconsin and was highest in the least advantaged counties in the state. Additional public health efforts must be directed toward the counties with the greater relative smoking burden in order to reduce these disparities. PMID- 26854315 TI - A Brief Clinical Update on Hepatitis C--The Essentials. AB - Infection with the hepatitis C virus (HCV) is a common cause of cirrhosis and liver failure and the most common indication for liver transplant in the United States. Based on the prevalence of HCV infection at 1.3% of the US population, there are an estimated 74,000 people living with HCV infection in the state of Wisconsin, the majority of whom are undiagnosed. HCV infections in Wisconsin have increased, reflecting the increasing use of intravenous heroin in the state. This review discusses up-to-date guidelines for screening, diagnosis, and treatment of HCV. New direct-acting antiviral medications have revolutionized the treatment of HCV with significantly improved outcomes. High cost and limited availability of these medications present challenges in overall management of HCV. PMID- 26854316 TI - Successful Treatment of Collagenous Gastritis in a Child With a Gluten-Free Diet. AB - Collagenous gastritis is a rarely encountered disease entity first described in 1989, and it is very rarely reported in children. We report the case of a 13-year old boy with clinical, endoscopic, and histological findings of collagenous gastritis who reported rapid and sustained symptom resolution on a gluten-free diet. PMID- 26854317 TI - Serving the State Through Medical Research. PMID- 26854318 TI - MetaStar Security Risk Assessments: HIPAA and Meaningful Use. PMID- 26854319 TI - OPD-Scan III: a repeatability and inter-device agreement study of a multifunctional device in emmetropia, ametropia, and keratoconus. AB - The purpose of this study was to test the measurements of a multifunctional device, the NIDEK OPD-Scan III in terms of repeatability and agreement with retinoscopy and Pentacam in cases with emmetropia, ametropia, and KCN (grade 1 3). We enrolled 170 eyes (40 in each group of emmetropia and ametropia, and 90 in the 3 KCN subgroups). Acquisitions were done twice by a single technician to check the intra class correlation, repeatability index, and precision. To assess agreement, we compared OPD-Scan III with retinoscopy and Pentacam results by two blinded technicians. All device functions had acceptable precision in groups with emmetropia, ametropia, and KCN1, except spherical error in ammetropics (0.97 D). In KCN2, repeatability was acceptable with the refractive function, topography, and ocular aberrations but was more than 1.0 D for corneal aberrations. In KCN3, repeatability was low for the refractive function and corneal spherical aberration. Refractive data were not convertible to those obtained by retinoscopy in any group. OPD-Scan III keratometry data were interchangeable with Pentacam counterparts in emmetropes, ammetropes, and KCN1. In KCN2, the OPD-Scan III Pentacam agreement for Kmax was 0.71 D, and there was 1.25 D difference in Kmin. No OPD-Scan III-Pentacam agreement was observed in KCN3. OPD- Scan III is a multifunctional device with acceptable repeatability in emmetropic, ammetropic, and KCN cases. Its measurements of corneal curvature and ocular aberrations are better than other functions. In cases with high degrees of refractive error and corneal irregularities, device repeatability and agreement with Pentacam is decreased. PMID- 26854320 TI - Comparison of the biometric formulas used for applanation A-scan ultrasound biometry. AB - The purpose of the study was to compare the accuracy of various biometric formulas for predicting postoperative refraction determined using applanation A scan ultrasound. This retrospective comparative study included 485 eyes that underwent uneventful phacoemulsification with intraocular lens (IOL) implantation. Applanation A-scan ultrasound biometry and postoperative manifest refraction were obtained in all eyes. Biometric data were entered into each of the five IOL power calculation formulas: SRK-II, SRK/T, Holladay I, Hoffer Q, and Binkhorst II. All eyes were divided into three groups according to axial length: short (<=22.0 mm), average (22.0-25.0 mm), and long (>=25.0 mm) eyes. The postoperative spherical equivalent was calculated and compared with the predicted refractive error using each biometric formula. The results showed that all formulas had significantly lower mean absolute error (MAE) in comparison with Binkhorst II formula (P < 0.01). The lowest MAE was obtained with the SRK-II for average (0.49 +/- 0.40 D) and short (0.67 +/- 0.54 D) eyes and the SRK/T for long (0.61 +/- 0.50 D) eyes. The highest postoperative hyperopic shift was seen with the SRK-II for average (46.8 %), short (28.1 %), and long (48.4 %) eyes. The highest postoperative myopic shift was seen with the Holladay I for average (66.4 %) and long (71.0 %) eyes and the SRK/T for short eyes (80.6 %). In conclusion, the SRK-II formula produced the lowest MAE in average and short eyes and the SRK/T formula produced the lowest MAE in long eyes. The SRK-II has the highest postoperative hyperopic shift in all eyes. The highest postoperative myopic shift is with the Holladay I for average and long eyes and SRK/T for short eyes. PMID- 26854321 TI - The innovation trap. PMID- 26854322 TI - alpha-Glucosidase and alpha-amylase inhibitors from seed oil: A review of liposoluble substance to treat diabetes. AB - One of the effective managements of diabetes mellitus, in particular, noninsulin dependent diabetes mellitus, is to retard the absorption of glucose by inhibition of carbohydrate hydrolyzing enzymes, such as alpha-glucosidase and alpha-amylase, in the digestive organs. Currently, there is renewed interest in plant-based medicines and functional foods modulating physiological effects in the inhibition of alpha-glucosidase and alpha-amylase. Accordingly, inhibitors of alpha glucosidase or alpha-amylase derived from various sources have also been isolated, and majority of phenolic compounds and their effects have been investigated in animals as well. As such, when the presence of alpha-glucosidase inhibitor in many foodstuffs was screened for, we found that vegetable seed oil also strongly inhibited alpha-glucosidase and alpha-amylase. Seed oil is an important source of liposoluble constituents with potential for inhibition of these enzymes, hence can also be used as therapeutic or functional food sources. Therefore, this review is aimed at highlighting the main liposoluble classes of alpha-glucosidase and alpha-amylase inhibitors, but it is not intended to be an exhaustive review on the subject. PMID- 26854323 TI - Erratum. PMID- 26854324 TI - Errata. PMID- 26854326 TI - Intravenous busulfan dose individualization - impact of modeling approach on dose recommendation. AB - TDM is intended to limit unintended consequences of drugs with narrow therapeutic indices. However, the application of different sampling strategies and pharmacokinetic approaches results in different dosing recommendations and ostensibly different outcomes. TDM approaches for intravenous busulfan dose individualization employ compartmental or non-compartmental modeling with anywhere from three to seven drug levels. This investigation was designed to examine the differences in dosing recommendations that arise in children (n = 30) when five different TDM approaches were employed. Significant differences in recommended doses between modeling strategies were observed. More importantly, the recommendations were discordant in 13 cases with at least one model recommending a dose adjustment in the opposite direction relative to the remaining models. The mathematical differences introduced by the application of different TDM approaches are not purely academic. Unification of busulfan TDM approaches should be considered to mitigate inconsistently applied dose adjustment, and facilitate comparisons of outcome, between clinical centers. PMID- 26854327 TI - Perivascular adipose tissue and inflammation. PMID- 26854325 TI - Environmental and occupational risk factors for progressive supranuclear palsy: Case-control study. AB - BACKGROUND: The cause of progressive supranuclear palsy (PSP) is largely unknown. Based on evidence for impaired mitochondrial activity in PSP, we hypothesized that the disease may be related to exposure to environmental toxins, some of which are mitochondrial inhibitors. METHODS: This multicenter case-control study included 284 incident PSP cases of 350 cases and 284 age-, sex-, and race-matched controls primarily from the same geographical areas. All subjects were administered standardized interviews to obtain data on demographics, residential history, and lifetime occupational history. An industrial hygienist and a toxicologist unaware of case status assessed occupational histories to estimate past exposure to metals, pesticides, organic solvents, and other chemicals. RESULTS: Cases and controls were similar on demographic factors. In unadjusted analyses, PSP was associated with lower education, lower income, more smoking pack-years, more years of drinking well water, more years living on a farm, more years living 1 mile from an agricultural region, more transportation jobs, and more jobs with exposure to metals in general. However, in adjusted models, only more years of drinking well water was significantly associated with PSP. There was an inverse association with having a college degree. CONCLUSIONS: We did not find evidence for a specific causative chemical exposure; higher number of years of drinking well water is a risk factor for PSP. This result remained significant after adjusting for income, smoking, education and occupational exposures. This is the first case-control study to demonstrate PSP is associated with environmental factors. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26854328 TI - Donor oocyte conception and pregnancy complications: a systematic review and meta analysis. AB - BACKGROUND: Observational studies showed that women with a donor oocyte (DO) pregnancy have an increased risk of pregnancy complications. OBJECTIVES: Systematic review and meta-analysis to compare pregnancy complications of DO pregnancy with autologous oocyte in vitro fertilisation (IVF), and whether DO pregnancy acts as an independent risk factor. SEARCH STRATEGY: Online searches of databases from 1 January 1980 to 31 January 2015 were performed using a set of relevant keywords. SELECTION CRITERIA: All studies comparing pregnancy complications of women with donor oocyte IVF and autologous oocyte IVF were included. DATA COLLECTION AND ANALYSIS: Data collected included demographics and pregnancy complications. Methodological quality assessment was performed using the Newcastle-Ottawa scale. Statistical analysis was performed using review manager 5.3 and stata 13.0. Meta-regression was performed for age. MAIN RESULTS: In total, 11 studies (n = 81 752) were included. Ten studies (n = 11 539) examined the primary outcome. The risk of developing hypertensive disorders in pregnancy was significantly higher for DO pregnancy (odds ratio, OR 3.92; 95% confidence interval, 95% CI 3.21-4.78). Further subgroup analysis for singleton and twin pregnancies showed that the risk was significantly higher for DO pregnancy in each group. Secondary outcomes including small for gestational age (OR 1.81), caesarean section (OR 2.71), and preterm delivery (OR 1.34) were significantly higher with DO pregnancy. Meta-regression for the covariate of age suggested that risk was independent of age. AUTHOR'S CONCLUSIONS: Donor oocyte pregnancy acts as an independent risk factor for pregnancy complications, including hypertensive disorders, small for gestational age, and preterm delivery. Women should be counselled carefully before undergoing DO-assisted conception. TWEETABLE ABSTRACT: Donor oocyte conception is an independent risk factor for obstetric complications. PMID- 26854329 TI - Transfer of antibiotic resistance from Enterococcus faecium of fermented meat origin to Listeria monocytogenes and Listeria innocua. AB - Listeria monocytogenes is an important foodborne pathogen that can cause infection in children, pregnant women, the immunocompromised and the elderly. Antibiotic resistance in this species would represent a significant public health problem since the organism has a high fatality/case ratio and resistance may contribute to failure of therapeutic treatment. This study was designed to explore whether the in vitro transferability of antibiotic resistance from enterococci to Listeria spp. could occur. It was found that 2/8 Listeria strains were able to acquire tetracycline resistance from Enterococcus faecium. Listeria monocytogenes GLM-2 acquired the resistance determinant tet(M) and additional streptomycin resistance through in vitro mating with Ent. faecium S27 isolated from commercial fermented dry sausage. Similarly, Listeria innocua became more resistant to tetracycline, but the genetic basis for this change was not confirmed. It has been suggested that enterococci may transfer antibiotic resistance genes via transposons to Listeria spp., and this may explain, in part, the origin of their antibiotic resistance. Thus, the presence of enterococci in food should not be ignored since they may actively contribute to enhanced antibiotic resistance of L. monocytogenes and other pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: Acquisition of antibiotic resistance by pathogenic bacteria in the absence of antibiotic pressure represents an unquantified threat to human health. In the present work resistance to tetracycline and streptomycin were transferred by nonplasmid-based conjugation from Enterococcus faecium isolated from fermented sausage to Listeria monocytogenes and Listeria innocua. Thus, natural transfer of antibiotic resistance to Listeria strains may occur in the future which reinforces the concern about the safety of enterococcal strains present in foods. PMID- 26854331 TI - Specimen preparation by ion beam slope cutting for characterization of ductile damage by scanning electron microscopy. AB - To investigate ductile damage in parts made by cold sheet-bulk metal forming a suited specimen preparation is required to observe the microstructure and defects such as voids by electron microscopy. By means of ion beam slope cutting both a targeted material removal can be applied and mechanical or thermal influences during preparation avoided. In combination with scanning electron microscopy this method allows to examine voids in the submicron range and thus to analyze early stages of ductile damage. In addition, a relief structure is formed by the selectivity of the ion bombardment, which depends on grain orientation and microstructural defects. The formation of these relief structures is studied using scanning electron microscopy and electron backscatter diffraction and the use of this side effect to interpret the microstructural mechanisms of voids formation by plastic deformation is discussed. A comprehensive investigation of the suitability of ion beam milling to analyze ductile damage is given at the examples of a ferritic deep drawing steel and a dual phase steel. PMID- 26854330 TI - Labelling Bacterial Nanocages with Photo-switchable Fluorophores. AB - The robustness and biocompatibility of bacterial nanocages holds promise for bio nanotechnologies. The propensity of these nano-carriers to penetrate cells has been demonstrated, which calls for the development of tracking strategies, both in vitro and in vivo. Here, we label bacterial nanocages with photo-switchable fluorophores, to facilitate their imaging by super-resolution microscopy. We demonstrate the functionalization of the encapsulin from Brevibacterium linens with a spiropyran, which is not fluorescent, by covalent attachment to the amine residues at the outer encapsulin shell. Upon alternating irradiation with ultraviolet and visible light, the spiropyran switches forth and back to its fluorescent merocyanine photo-isomer and thus the fluorescence can be switched on and off, reversibly. We also show that the bacterial compartments preserve their structural integrity upon covalent modification and over at least five irradiation cycles. PMID- 26854333 TI - Phase-Change Memory Materials by Design: A Strain Engineering Approach. AB - Van der Waals heterostructure superlattices of Sb2 Te1 and GeTe are strain engineered to promote switchable atomic disordering, which is confined to the GeTe layer. Careful control of the strain in the structures presents a new degree of freedom to design the properties of functional superlattice structures for data storage and photonics applications. PMID- 26854334 TI - Is a punch biopsy reliable in subtyping basal cell carcinoma? A systematic review. PMID- 26854332 TI - Impaired skeletal health in patients with chronic atrophic gastritis. AB - OBJECTIVE: In chronic atrophic gastritis (CAG), destruction of gastric parietal cells causes anacidity and hypergastrinemia. Use of proton pump inhibitors, which also induces gastric anacidity, is associated with increased fracture rates. Our objectives were to study possible differences in bone mineral density (BMD) and bone quality in patients with CAG compared to controls. MATERIAL AND METHODS: We performed a cross-sectional study on 17 CAG patients aged 54 +/- 13 years and 41 sex- and age-matched controls. Lumbar and femoral BMD and bone quality assessed by lumbar trabecular bone score (TBS) were measured by DXA, and bone material strength (BMS) by microindentation of the tibia. Serum bone markers (CTX, P1NP, sclerostin, osteocalcin, OPG, RANKL) were analyzed. RESULTS: We found lower lumbar BMD Z-score (-0.324 +/- 1.096 versus 0.456 +/- 1.262, p = 0.030), as well as a higher frequency of osteoporosis at the lumbar spine (p = 0.046) and osteopenia at total hip (p = 0.019) in patients compared to controls. In a post hoc subgroup analysis, we observed that the differences were confined to the male patients. TBS also tended to be lower in male patients (p = 0.059), while BMS did not differ between the groups. Osteocalcin, sclerostin, OPG, and OPG/RANKL ratio were lower in patients compared to controls, while CTX and P1NP did not differ between the groups. CONCLUSIONS: We observed lower lumbar BMD, increased frequency of osteopenia and osteoporosis in male, but not female patients with CAG. Bone markers suggest a decrease in bone formation and increased bone resorption in CAG patients compared to controls. PMID- 26854335 TI - A case of brucellosis presenting with pericardial and pleural effusion. AB - Brucellosis is a worldwide zoonotic infection with a diverse clinical presentation. Pericardial and pleural involvement is rare in brucellosis. There is no presentation with pleural and pericardial effusion in childhood brusellosis. In endemic countries Brucellosis must thought as an unknown etiology of pericardial and pleural effusion. PMID- 26854336 TI - Easily doped p-type, low hole effective mass, transparent oxides. AB - Fulfillment of the promise of transparent electronics has been hindered until now largely by the lack of semiconductors that can be doped p-type in a stable way, and that at the same time present high hole mobility and are highly transparent in the visible spectrum. Here, a high-throughput study based on first-principles methods reveals four oxides, namely X2SeO2, with X = La, Pr, Nd, and Gd, which are unique in that they exhibit excellent characteristics for transparent electronic device applications - i.e., a direct band gap larger than 3.1 eV, an average hole effective mass below the electron rest mass, and good p-type dopability. Furthermore, for La2SeO2 it is explicitly shown that Na impurities substituting La are shallow acceptors in moderate to strong anion-rich growth conditions, with low formation energy, and that they will not be compensated by anion vacancies VO or VSe. PMID- 26854337 TI - The first reported Florida clade 1 virus in the Nordic countries, isolated from a Swedish outbreak of equine influenza in 2011. AB - Equine Influenza Virus (EIV) is a major cause of respiratory disease in horses and the virus constantly undergoes antigenic drift. Here we characterize and describe the HA1 and the NA genes of H3N8 within samples obtained from outbreaks in Sweden during November-December 2011. Both clade 1 and clade 2 viruses of the Florida sublineage were identified. The index case of clade 2 was transported to Sweden from Spain through the Netherlands, whereas the clade 1 had its origin from a Swedish stud farm. The clade 1 virus was efficiently spread between training yards by unvaccinated young horses, but vaccinated horses were also presented with clinical signs of respiratory disease. No virus of the Eurasian lineage was isolated during this outbreak. Clade 1 has previously been described in outbreaks in numerous of other countries, but this is the first time it has been detected in Sweden. The results from this study shows the importance of including both clade 1 and clade 2 of the Florida sublineage in equine influenza vaccines, supporting the ESP and OIE recommendations. PMID- 26854338 TI - Molecular and antibiotic susceptibility characterization of Aerococcus viridans isolated from porcine urinary infection. AB - Aerococcus viridans has been reported as a human and animal pathogen causing urinary tract infection, arthritis, pneumonia, meningitis and endocarditis. Routinely, A. viridans is not surveyed in clinical diagnosis laboratories and commonly is misidentified as other bacteria. There is no concrete data on the prevalence and impact of the pathogen to both human and animal health. In the present study, we report the isolation and molecular and antibiotic susceptibility characterization of A. viridans strains from porcine urinary infections. A total of 22 isolates were identified as A. viridans by MALDI-TOF MS and confirmed by 16S rRNA gene sequencing. Isolates were genotyped by single enzyme amplified fragments length polymorphism (SE-AFLP) that resulted in 19 clusters of which 81.2% were composed by single isolates. The high genetic heterogeneity corroborates previous studies and appears to be a particularity of A. viridans. The minimal inhibitory concentration (MIC) values also presented variability especially for ceftiofur, fluoroquinolones and aminoglycosides. The high MICs of aminoglycosides, tetracyclines and macrolides seen among the A. viridans corroborate previous reports and the widespread veterinary usage of these antibiotics demand attention for the implication of A. viridans infection to both human and animal health. PMID- 26854339 TI - Characterization of monoclonal antibodies against feline coronavirus accessory protein 7b. AB - Feline coronaviruses (FCoVs) encode five accessory proteins termed 3a, 3b, 3c, 7a and 7b of unknown function. These proteins are dispensable for viral replication in vitro but are supposed to play a role in virulence. In the current study, we produced and characterized 7b-specific monoclonal antibodies (mAbs). A recombinant form of the 7b protein was expressed as a fusion protein in Escherichia coli, purified by immobilized metal affinity chromatography and used as immunogen. Two hybridoma lines, 5B6 and 14D8, were isolated that expressed mAbs that recognized 7b proteins of both FCoV serotypes. Using an extensive set of N- and C-terminally truncated 7b proteins expressed in E. coli and a synthetic peptide, the binding sites of mAbs 5B6 and 14D8 were mapped to an 18-residue region that comprises the only potential N-glycosylation site of the FCoV 7b protein. The two mAbs were suitable to detect a 24-kDa protein, which represents the nonglycosylated form of 7b in FCoV-infected cells. We speculate that glycosylation of 7b is part of the viral evasion strategy to prevent an immune response against this antigenic site. PMID- 26854340 TI - Linear antigenic mapping of flagellin (FliC) from Salmonella enterica serovar Enteritidis with yeast surface expression system. AB - Salmonella enterica serovar Enteritidis (S. Enteritidis) is a major cause of food borne illness around the world and can have significant health implications in humans, poultry and other animals. Flagellin (FliC) is the primary component of bacterial flagella. It has been shown that the FliC of S. Enteritidis is a significant antigenic structure and can elicit strong humoral responses against S. Enteritidis infection in chickens. Here, we constructed a FliC antigen library using a yeast surface expression system. Yeast cells expressing FliC peptide antigens were labeled with chicken sera against S. Enteritidis and sorted using FACS. The analyses of FliC peptides revealed that the FliC linear antigenicity in chickens resided on three domains which were able to elicit strong humoral responses in vivo. Animal experiments further revealed that the antibodies elicited by these antigenic domains were able to significantly inhibit the invasion of S. Enteritidis into the liver and spleen of chickens. These findings will facilitate our better understanding of the humoral responses elicited by FliC in chickens upon infection by S. Enteritidis. PMID- 26854341 TI - Shiga toxin-producing Escherichia coli (STEC): Zoonotic risks associated with psittacine pet birds in home environments. AB - Psittacidae are frequently bred as pets worldwide, but little is known about the zoonotic risks of these animals. The objective of this study was to investigate the presence of Shiga toxin-producing Escherichia coli (STEC) in the feces of psittacine birds housed as pets. A total of 171 fecal samples (67 cockatiels, 59 budgerigars, and 45 agapornis) were cultured. Forty-two (E. coli) strains were identified, and the presence of the eae, stx1, and stx2 genes was determined using PCR. The antimicrobial resistance profiles of the STEC strains were determined using the disk diffusion method and phylogenetic analysis according to the new Clermont phylotyping method. Using these methods, 19.4% (8/42) of the STEC strains were determined to be positive for the eae and stx2 genes. The results revealed a STEC frequency of 4.6% in the birds (8/171), with a percentage of 8.47% in budgerigars (5/59), 4.47% in cockatiels (3/67), and 0% in agapornis (0/45). None of the STEC isolates belonged to the O157 serogroup. Most of the strains were classified as sensitive to the 18 antibiotics tested. None of the strains exhibited a multiresistance profile. In the phylogenetic analysis, two strains were classified as non-typeable, three were classified as B2, two were classified as F, and one was classified as Clade I. Seven of the eight STEC strains showed a clonal profile using AFLP. E. coli strains that are stx2(+) plus eae(+) are usually associated with severe human diseases such as hemorrhagic colitis and hemolytic-uremic syndrome. The STEC-positive results indicate the zoonotic risk of breeding psittacidae in home environments. PMID- 26854342 TI - Co-infection of classic swine H1N1 influenza virus in pigs persistently infected with porcine rubulavirus. AB - Porcine rubulavirus (PorPV) and swine influenza virus infection causes respiratory disease in pigs. PorPV persistent infection could facilitate the establishment of secondary infections. The aim of this study was to analyse the pathogenicity of classic swine H1N1 influenza virus (swH1N1) in growing pigs persistently infected with porcine rubulavirus. Conventional six-week-old pigs were intranasally inoculated with PorPV, swH1N1, or PorPV/swH1N1. A mock-infected group was included. The co-infection with swH1N1 was at 44 days post-infection (DPI), right after clinical signs of PorPV infection had stopped. The pigs of the co-infection group presented an increase of clinical signs compared to the simple infection groups. In all infected groups, the most recurrent lung lesion was hyperplasia of the bronchiolar-associated lymphoid tissue and interstitial pneumonia. By means of immunohistochemical evaluation it was possible to demonstrate the presence of the two viral agents infecting simultaneously the bronchiolar epithelium. Viral excretion of PorPV in nasal and oral fluid was recorded at 28 and 52 DPI, respectively. PorPV persisted in several samples from respiratory tissues (RT), secondary lymphoid organs (SLO), and bronchoalveolar lavage fluid (BALF). For swH1N1, the viral excretion in nasal fluids was significantly higher in single-infected swH1N1 pigs than in the co-infected group. However, the co-infection group exhibited an increase in the presence of swH1N1 in RT, SLO, and BALF at two days after co-infection. In conclusion, the results obtained confirm an increase in the clinical signs of infection, and PorPV was observed to impact the spread of swH1N1 in analysed tissues in the early stage of co-infection, although viral shedding was not enhanced. In the present study, the interaction of swH1N1 infection is demonstrated in pigs persistently infected with PorPV. PMID- 26854343 TI - Characterization of specific antigenic epitopes and the nuclear export signal of the Porcine circovirus 2 ORF3 protein. AB - Porcine circovirus 2 (PCV2) is the etiological agent of postweaning multisystemic wasting syndrome. PCV2 ORF3 protein is a nonstructural protein known to induce apoptosis, but little is known about the biological function of ORF3 protein. Therefore, we undertook this study to map ORF3 protein epitopes recognized by a panel of monoclonal antibodies (mAbs) and to characterize putative nuclear localization (NLS) and nuclear export (NES) sequences in ORF3. The linear epitopes targeted by two previously published mAbs 3B1 and 1H3 and a novel mouse mAb 3C3 were defined using overlapping pools of peptides. Here, we find that ORF3 in PCV2 infected cells contains a conformational epitope targeted by the antibody 3C3, which is distinct from linear epitopes recognized by the antibodies 3B1 and 1H3 in recombinant ORF3 protein. These results suggest that the linear epitope recognized by 3B1 and 1H3 is masked in PCV2 infected cells, and that the conformational epitope is unique to PCV2 infection. Furthermore, we find that ORF3 protein expressed in cytoplasm in early stages of PCV2 infection and then accumulated in nucleus over time. Moreover, we localize a NES at the N-terminus (residues 1-35aa) of ORF3 which plays critical role in nuclear export activity. These findings provide a novel insight that deepens our understanding of the biological function of PCV2 ORF3. PMID- 26854344 TI - A model to investigate the optimal seeder-to-naive ratio for successful natural Mycoplasma hyopneumoniae gilt exposure prior to entering the breeding herd. AB - Due to the significance of Mycoplasma hyopneumoniae as a swine respiratory pathogen, acclimation measures are taken into consideration when obtaining replacement gilts from negative sources to be introduced to endemically infected herds. The aim of this study was to evaluate the optimum seeder-to-naive gilt ratio in a 4-week period for successful natural exposure to M. hyopneumoniae. Sixty gilts were divided in two groups, 21 2-week old seeder gilts were inoculated with M. hyopneumoniae, and 39 aged-matched naive gilts were exposed to the seeders during a 4-week period. The exposure was set by dividing the gilts into six groups of 10 with different ratios of seeder-to-naive, from 1:9 until 6 seeders and 4 naive gilts. Laryngeal swabs, oral fluids and blood samples were collected from all gilts prior to, during and after inoculation and exposure. Infection in seeders was confirmed by development of clinical signs, seroconversion post-inoculation, and detection of M. hyopneumoniae genetic material. Naive were considered positive after 4 weeks if M. hyopneumoniae was detected on bronchial swab or fixed lung tissue. As result, 33% (3/9) naive gilts were positive in the 1:9 ratio, 75% (6/8) in 2:8, 28% (2/7) in 3:7, 33% (2/6) in 4:6, 80% (4/5) in 5:5 and 100% (4/4) in the 6:4 ratio. The estimated transmission rate (beta) and expected probability of infection (psi) were 1.28 per pig/week and 0.6, respectively. In this study, six seeders were required in a group of 10 gilts for successful exposure to M. hyopneumoniae in a 4-week exposure period. PMID- 26854345 TI - Acute phase protein and antioxidant responses in dogs with experimental acute monocytic ehrlichiosis treated with rifampicin. AB - There is currently lack of information on the changes of acute phase proteins (APP) and antioxidant markers and their clinical relevance as treatment response indicators in canine monocytic ehrlichiosis (CME). The objective of this study was to investigate the patterns of C-reactive protein (CRP), haptoglobin (Hp), ferritin and paraoxonase-1 (PON-1) during treatment of dogs with acute CME with rifampicin. Blood serum samples from ten Beagle dogs with experimental acute CME were retrospectively examined. Five dogs (Group A) were treated with rifampicin (10mg/Kg/24h), per os, for 3 weeks and 5 dogs (Group B) received no treatment (infected controls). Two Beagle dogs served as uninfected controls. Blood serum samples were serially examined prior to Ehrlichia canis inoculation and on post inoculation days 14, 21, 28, 35 and 42. Significant changes of CRP, Hp, ferritin and PON-1 values were found in the majority of infected dogs. However, their concentrations did not differ between the two groups during the treatment observation period. The results of this study indicate that although several APP and PON-1 tend to significantly change in the majority of dogs with acute CME, they were of limited clinical relevance as treatment response indicators in this experimental setting. PMID- 26854346 TI - Streptococcus agalactiae in the environment of bovine dairy herds--rewriting the textbooks? AB - Many free-stall bovine dairy herds in Norway fail to eradicate Streptococcus agalactiae despite long-term control measures. In a longitudinal study of 4 free stall herds with automatic milking systems (AMS), milk and extramammary sites were sampled 4 times with 1-2 month intervals. Composite milk, rectal- and vaginal swabs were collected from dairy cows; rectal swabs from heifers and young stock; rectal- and tonsillar swabs from calves; and environmental swabs from the AMS, the floors, cow beds, watering and feeding equipment. A cross sectional study of 37 herds was also conducted, with 1 visit for environmental sampling. Fifteen of the herds were known to be infected with S. agalactiae while the remaining 22 had not had evidence of S. agalactiae mastitis in the preceding 2 years. All samples were cultured for S. agalactiae, and selected isolates (n=54) from positive herds were genotyped by Multi Locus Sequence Typing (MLST). Results show that the bovine gastrointestinal tract and the dairy cow environment are reservoirs of S. agalactiae, and point to the existence of 2 transmission cycles; a contagious transmission cycle via the milking machine and an oro-fecal transmission cycle, with drinking water as the most likely vehicle for transmission. Ten sequence types were identified, and results suggest that strains differ in their ability to survive in the environment and transmit within dairy herds. Measures to eradicate S. agalactiae from bovine dairy herds should take into account the extra-mammary reservoirs and the potential for environmental transmission of this supposedly exclusively contagious pathogen. PMID- 26854347 TI - The viral non-structural protein 1 alpha (Nsp1alpha) inhibits p53 apoptosis activity by increasing murine double minute 2 (mdm2) expression in porcine reproductive and respiratory syndrome virus (PRRSV) early-infected cells. AB - Apoptosis is one of the most important mechanisms of pathogenesis in porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells. The tumor suppressor p53 plays a critical role in apoptotic induction in viral infections. In the present study, we found that p53 activity was inhibited at the early stage of PRRSV infection in both the highly pathogenic (HP) and lowly pathogenic (LP) PRRSV isolates. Bax expression showed a similar change pattern to that of p53. Murine double minute 2 (mdm2) expressed higher in PRRSV-infected cells than in uninfected cells at the early stage of infection and promoted p53 degradation. We show for the first time that the non-structural protein 1 alpha (Nsp1alpha) of PRRSV is a negative regulator of p53 activity through increasing mdm2 expression and p53 ubiquitination, while p53 is inhibitory to PRRSV replication at the early stage of infection. We conclude that PRRSV manipulates the host factors mdm2 and p53 via its Nsp1alpha for increased replication at the early stage of infection. These provide a novel perspective to understand the interaction between apoptosis and replication of PRRSV. PMID- 26854348 TI - Transferable genes putatively conferring elevated minimum inhibitory concentrations of narasin in Enterococcus faecium from Swedish broilers. AB - The minimum inhibitory concentration (MIC) of the polyether ionophore antibiotic narasin is elevated in a large proportion of Enterococcus faecium from Swedish broilers. The aim of this study was to identify gene(s) responsible for these elevated MICs. Six plasmids, four conferring vancomycin resistance and elevated MIC of narasin and two only conferring resistance to vancomycin, were sequenced. The genes for a putative mechanism for elevated MIC of narasin was used to design a PCR assay which in turn was used to screen 100 isolates of E. faecium from Swedish broilers. A 5.9 kb area was only found in the plasmids transferring elevated MIC of narasin. This area included two genes coding for an ABC-type transporter; an 'ABC transporter permease protein' and an 'ABC-type multidrug transport system, ATPase component'. These genes are known to confer resistance to the ionophore tetronasin. PCR investigation confirmed a correlation between the presence of the genes and a MIC of narasin >= 2 mg/L. The results of this study indicate that the ABC permease together with the ABC ATPase are responsible for the elevated MIC of narasin present among E. faecium in Swedish broilers. To our knowledge, this is the first report of a putative transferable mechanism for elevated MIC of narasin. PMID- 26854349 TI - Antiviral activities of 2,6-diaminopurine-based acyclic nucleoside phosphonates against herpesviruses: In vitro study results with pseudorabies virus (PrV, SuHV 1). AB - Pseudorabies virus (PrV), a causative agent of Aujeszky's disease, is deadly to most mammals with the exception of higher primates and men. This disease causes serious economic loses among farm animals, especially pigs, yet many European countries are today claimed to be Aujeszky's disease free because of the discovery of an efficient vaccination for pigs. In reality, the virus is still present in wild boar. Current vaccines are neither suitable for dogs nor are there anti-PrV drugs approved for veterinary use. Therefore, the disease still represents a high threat, particularly for expensive hunting dogs that can come into close contact with infected boars. Here we report on the anti-PrV activities of a series of synthetic diaminopurine-based acyclic nucleoside phosphonate (DAP ANP) analogues. Initially, all synthetic DAP-ANPs under investigation are shown to exhibit minimal cytotoxicity by MTT and XTT tests (1-100MUM range). Thereafter in vitro infection models are established using PrV virus SuHV-1, optimized on PK 15 and RK-13 cell lines. Out of the six DAP-ANP analogues tested, analogue VI functionalized with a cyclopropyl group on the 6-amino position of the purine ring proves the most effective antiviral DAP-ANP analogue against PrV infection, aided by sufficient hydrophobic character to enhance bioavailability to its cellular target viral DNA-polymerase. Four other DAP-ANP analogues with functional groups introduced to the C2'position are shown ineffective against PrV infection, even with favourable hydrophobic properties. Cidofovir((r)), a drug approved against various herpesvirus infections, is found to exert only low activity against PrV in these same in vitro models. PMID- 26854350 TI - Characterization and pathogenic role of outer membrane vesicles produced by the fish pathogen Piscirickettsia salmonis under in vitro conditions. AB - Piscirickettsia salmonis is one of the major fish pathogens affecting Chilean aquaculture. This Gram-negative bacterium is highly infectious and is the etiological agent of Piscirickettsiosis. Little is currently known about how the virulence factors expressed by P. salmonis are delivered to host cells. However, it is known that several Gram-negative microorganisms constitutively release outer membrane vesicles (OMVs), which have been implicated in the delivery of virulence factors to host cells. In this study, OMVs production by P. salmonis was observed during infection in CHSE-214 cells and during normal growth in liquid media. The OMVs were spherical vesicles ranging in size between 25 and 145 nm. SDS-PAGE analysis demonstrated that the protein profile of the OMVs was similar to the outer membrane protein profile of P. salmonis. Importantly, the bacterial chaperonin Hsp60 was found in the OMVs of P. salmonis by Western-blot and LC-MS/MS analyses. Finally, in vitro infection assays showed that purified OMVs generated a cytopathic effect on CHSE-214 cells, suggesting a role in pathogenesis. Therefore, OMVs might be an important vehicle for delivering effector molecules to host cells during P. salmonis infection. PMID- 26854351 TI - Feature co-localization landscape of the human genome. AB - Although feature co-localizations could serve as useful guide-posts to genome architecture, a comprehensive and quantitative feature co-localization map of the human genome has been lacking. Herein we show that, in contrast to the conventional bipartite division of genomic sequences into genic and inter-genic regions, pairwise co-localizations of forty-two genomic features in the twenty two autosomes based on 50-kb to 2,000-kb sequence windows indicate a tripartite zonal architecture comprising Genic zones enriched with gene-related features and Alu-elements; Proximal zones enriched with MIR- and L2-elements, transcription factor-binding-sites (TFBSs), and conserved-indels (CIDs); and Distal zones enriched with L1-elements. Co-localizations between single-nucleotide polymorphisms (SNPs) and copy-number-variations (CNVs) reveal a fraction of sequence windows displaying steeply enhanced levels of SNPs, CNVs and recombination rates that point to active adaptive evolution in such pathways as immune response, sensory perceptions, and cognition. The strongest positive co localization observed between TFBSs and CIDs suggests a regulatory role of CIDs in cooperation with TFBSs. The positive co-localizations of cancer somatic CNVs (CNVT) with all Proximal zone and most Genic zone features, in contrast to the distinctly more restricted co-localizations exhibited by germline CNVs (CNVG), reveal disparate distributions of CNVTs and CNVGs indicative of dissimilarity in their underlying mechanisms. PMID- 26854352 TI - What Is the True Structure of D609, a Widely Used Lipid Related Enzyme Inhibitor? AB - D609 (1) has been used as a lipid-related enzyme inhibitor during the past three decades. Although it has eight possible stereoisomers, no systematic research considering its chirality has been performed. In this paper, eight possible chiral alcohols as direct precursors of D609 were synthesized, and their stereochemistries were elucidated by a vibrational circular dichroism (VCD) technique. Phosphatidylcholine-specific phospholipase C and sphingomyelin synthase inhibition assays of these isomers showed considerable differences in their activities. PMID- 26854353 TI - Regulation of Itch and Nedd4 E3 Ligase Activity and Degradation by LRAD3. AB - Itch and Nedd4 are members of the Nedd4 family of E3 ubiquitin ligases that are important in a number of biological processes. Precise regulation of their enzymatic activity is required for normal physiological function. Nedd4-like E3 ligases exist in an inactive form resulting from intramolecular interactions of their catalytic HECT domain with their WW domains. We identified the low-density lipoprotein receptor class A domain containing 3 (LRAD3), a member of the LDL receptor family, as a potent activator of Itch and Nedd4 as evidenced by their increased auto-ubiquitination when bound to LRAD3. LRAD3 contains two PPxY motifs within its intracellular domain, both of which can bind to the WW domains on Itch and other Nedd4 family members with high affinity. Mutational analysis revealed that binding of Itch to the terminal LRAD3 PPxY motif is required to promote its auto-ubiquitination. We also determined that association of Itch and Nedd4 with LRAD3 leads to increased auto-ubiquitination and subsequent degradation through proteasome-mediated processes. Our findings reveal that LRAD3 is a component of pathways that function effectively to modulate Itch and Nedd4 auto-ubiquitination and levels. The identification of potential ligands for LRAD3 that may modulate LRAD3-induced activation of Itch and Nedd4 is likely to identify additional novel substrates and cellular functions for these important E3 ligases. PMID- 26854354 TI - Gender difference in outcomes following trauma-focused interventions for posttraumatic stress disorder: Systematic review and meta-analysis. AB - OBJECTIVE: Currently, there is a lack of evidence on whether women and men respond differently to trauma-focused psychological treatments for posttraumatic stress disorder (PTSD). This study was a systematic review and meta-analysis to examine whether gender is associated with response to trauma-focused psychological interventions for PTSD. METHOD: The Cochrane Collaboration systematic review methodology (Higgins & Green, 2011) was used as a guide for this study. Randomized controlled trials comparing trauma-focused interventions for PTSD with comparison conditions were identified in a literature review. RESULTS: Forty-eight randomized controlled trials were included in the meta analysis: 25 had a mixed gender sample, 18 were female only, and 5 were male only. There was evidence that women had greater reductions than men in the primary outcome measure of clinician-rated PTSD symptoms when trauma-focused psychological interventions were compared with any comparison condition at both postintervention and short-term follow-up. This finding was supported by a direct effects meta-analysis of studies that provided data on both females and males. CONCLUSIONS: The current findings support a gender difference in outcomes following trauma-focused psychological interventions for PTSD. Future research should seek to identify specific factors related to gender that facilitate or inhibit response to these interventions. (PsycINFO Database Record PMID- 26854355 TI - Group-delivered cognitive/exposure therapy for PTSD in women veterans: A randomized controlled trial. AB - OBJECTIVE: Group delivery of posttraumatic stress disorder (PTSD) treatment has several advantages, however group research is not comparable to individual trials. This study extends the group literature by improving methodology in examining the efficacy of a 3-module (cognitive, exposure, skills) group treatment for PTSD, establishes a format for the delivery of group exposure therapy, and compares 3 treatment modules within the group. METHOD: Eighty-six Operation Enduring Freedom (OEF)/Operation Iraqi Freedom (OIF) women veterans were randomized to a 16-week, 3-member group treatment (Tx) or a waitlist (WL) condition. The primary (Clinician Administered PTSD Scale [CAPS]) and secondary (Medical Outcomes Study Short Form-36 [SF-36], Quality of Life Inventory [QOLI], and PTSD Checklist [PCL]) outcome measures were administered at baseline, post Tx/WL, and at 3- and 6-months post Tx (PCL additionally at pre/post for each treatment module). RESULTS: PTSD symptoms significantly improved in Tx arm participants (p < .001, ES = 1.72; unit of analysis group: n = 14), as did mental and physical life functioning (SF-36; p < .001), and quality of life (QOLI; p < .001). The WL significantly improved on the SF-36 (mental; p = .04) and QOLI (p = .02). Clinical improvement (CAPS) in the Tx arm reflected a treatment response (>=10-point decrease) in 77% and loss of PTSD diagnosis (<45) in 52% of participants, comparable to individual prolonged exposure (PE) treatment. Finally, PCL scores significantly lowered in exposure and cognitive modules. CONCLUSIONS: This study supports the use of group format for PTSD with 3 modules using improved methodology, with a novel, 3-member group which allows repeated in session weekly imaginal exposures. The results suggest future examination of group delivered PE. (PsycINFO Database Record PMID- 26854356 TI - Insight into the Amino-Type Excited-State Intramolecular Proton Transfer Cycle Using N-Tosyl Derivatives of 2-(2'-Aminophenyl)benzothiazole. AB - Studies have been carried out to gain insight in to an overall excited-state proton transfer cycle for a series of N-tosyl derivatives of 2-(2' aminophenyl)benzothiazole. The results indicate that followed by ultrafast (<150 fs) excited-state intramolecular proton transfer (ESIPT), the titled compounds undergo rotational isomerization along the C1-C1' bond. For the model compound 2 (2'-tosylaminophenyl)benzothiazole (PBT-NHTs) the subsequent cis-trans isomerization process in both triplet and ground states are probed by nanosecond transient absorption (TA) and two-step laser-induced fluorescence (TSLIF) spectroscopy. Both TA and TSLIF results indicate the existence of a long-lived trans-tautomer species in the ground state with a lifetime of few microseconds. The experimental results correlate well with the theoretical approach, which suggests that PBT-NHTs proton transfer tautomer generated in the excited state undergoes intramolecular C1-C1' rotation to ~100 degrees between benzothiazole and phenyl moieties in which the energetics for the S1 and T1 states are nearly identical. As a result, the intersystem crossing between S1 and T1 states serves as a fast deactivation pathway for the excited-state cis-tautomer to channel into both cis- and trans-tautomer in their respective T1 states, followed by the dominant T1-S0 radiationless deactivation to populate the trans-tautomer in the ground state. The trans-tautomer species in the S0 state proceeds with intermolecular double proton transfer to regenerate the cis-normal form. An overall proton-transfer cycle describing the amino-type ESIPT and the subsequent isomerization processes is thus depicted in detail. PMID- 26854357 TI - Plasmon-Mediated Two-Photon Photoluminescence-Detected Circular Dichroism in Gold Nanosphere Assemblies. AB - We report plasmon-mediated two-photon photoluminescence (TPPL)-detected circular dichroism (CD) from colloidal metal nanoparticle assemblies. Two classes of solid gold nanosphere (SGN) dimers--heterodimers and homodimers--were examined using polarization-resolved TPPL, second harmonic generation (SHG), and one-photon photoluminescence (OPPL). Unambiguous CD was detected in both the TPPL and SHG signals, and the magnitudes of the CD responses in these measurements showed agreement for individual nanostructures. Heterodimers gave larger CD responses (average TPPL-CDR = 0.62 +/- 0.33; average SHG-CDR = 0.51 +/- 0.21) than homodimers (average TPPL-CDR = 0.19 +/- 0.04; average SHG-CDR = 0.18 +/- 0.06). OPPL-CD was not detected for either structure. Analysis of dimer emission properties suggested the CD responses were determined by properties of the one photon-resonant mode excited by the laser. Average TPPL signals were (4.3 +/- 0.6)* larger than those for SHG. Because signal amplitude is a primary determinant for spatial accuracies and precisions obtained from optical microscopy, CD contrast generated from plasmon-mediated TPPL, which we report for the first time, can extend the suite of super-resolution imaging techniques. PMID- 26854358 TI - Extensive Dark Biological Production of Reactive Oxygen Species in Brackish and Freshwater Ponds. AB - Within natural waters, photodependent processes are generally considered the predominant source of reactive oxygen species (ROS), a suite of biogeochemically important molecules. However, recent discoveries of dark particle-associated ROS production in aquatic environments and extracellular ROS production by various microorganisms point to biological activity as a significant source of ROS in the absence of light. Thus, the objective of this study was to explore the occurrence of dark biological production of the ROS superoxide (O2(-)) and hydrogen peroxide (H2O2) in brackish and freshwater ponds. Here we show that the ROS superoxide and hydrogen peroxide were present in dark waters at comparable concentrations as in sunlit waters. This suggests that, at least for the short-lived superoxide species, light-independent processes were an important control on ROS levels in these natural waters. Indeed, we demonstrated that dark biological production of ROS extensively occurred in brackish and freshwater environments, with greater dark ROS production rates generally observed in the aphotic relative to the photic zone. Filtering and formaldehyde inhibition confirmed the biological nature of a majority of this dark ROS production, which likely involved phytoplankton, particle-associated heterotrophic bacteria, and NADH-oxidizing enzymes. We conclude that biological ROS production is widespread, including regions devoid of light, thereby expanding the relevance of these reactive molecules to all regions of our oxygenated global habit. PMID- 26854359 TI - Cobalt-Catalyzed Enantioselective Hydrogenation of Minimally Functionalized Alkenes: Isotopic Labeling Provides Insight into the Origin of Stereoselectivity and Alkene Insertion Preferences. AB - The asymmetric hydrogenation of cyclic alkenes lacking coordinating functionality with a C1-symmetric bis(imino)pyridine cobalt catalyst is described and has been applied to the synthesis of important substructures found in natural products and biologically active compounds. High activities and enantioselectivities were observed with substituted benzo-fused five-, six-, and seven-membered alkenes. The stereochemical outcome was dependent on both the ring size and exo/endo disposition. Deuterium labeling experiments support rapid and reversible 2,1 insertion that is unproductive for generating alkane product but accounts for the unusual isotopic distribution in deuterated alkanes. Analysis of the stereochemical outcome of the hydrogenated products coupled with isotopic labeling, stoichiometric, and kinetic studies established 1,2-alkene insertion as both turnover limiting and enantiodetermining with no evidence for erosion of cobalt alkyl stereochemistry by competing beta-hydrogen elimination processes. A stereochemical model accounting for the preferred antipodes of the alkanes is proposed and relies on the subtle influence of the achiral aryl imine substituent on the cobalt catalyst. PMID- 26854360 TI - The contribution of genomics to the study of Q fever. AB - Coxiella burnetii is the etiological agent of Q fever, a worldwide zoonosis that can result in large outbreaks. The birth of genomics and sequencing of C. burnetii strains has revolutionized many fields of study of this infection. Accurate genotyping methods and comparative genomic analysis have enabled description of the diversity of strains around the world and their link with pathogenicity. Genomics has also permitted the development of qPCR tools and axenic culture medium, facilitating the diagnosis of Q fever. Moreover, several pathophysiological mechanisms can now be predicted and therapeutic strategies can be determined thanks to in silico genome analysis. An extensive pan-genomic analysis will allow for a comprehensive view of the clonal diversity of C. burnetii and its link with virulence. PMID- 26854361 TI - Factors associated with experienced discrimination among people using mental health services in England. AB - BACKGROUND: Research has found considerable variation in how far individuals with a diagnosis of mental illness experience discrimination. AIMS: This study tested four hypotheses: (i) a diagnosis of schizophrenia will be associated with more discrimination than depression, anxiety or bipolar disorder; (ii) people with a history of involuntary treatment will report more discrimination than people without; (iii) higher levels of avoidance behaviour due to anticipated discrimination will be associated with higher levels of discrimination and (iv) longer time in contact with services will be associated with higher levels of discrimination. METHOD: Three thousand five hundred and seventy-nine people using mental health services in England took part in structured telephone interviews about discrimination experiences. RESULTS: A multiple regression model found that study year, age, employment status, length of time in mental health services, disagreeing with the diagnosis, anticipating discrimination in personal relationships and feeling the need to conceal a diagnosis from others were significantly associated with higher levels of experienced discrimination. CONCLUSION: Findings suggest that discrimination is not related to specific diagnoses but rather is associated with mental health problems generally. An association between unemployment and discrimination may indicate that employment protects against experiences of discrimination, supporting efforts to improve access to employment among people with a diagnosis of mental illness. PMID- 26854362 TI - Therapy implications for the role of IL-21 in lupus. PMID- 26854363 TI - Guiding pharmacist clinical interviews: a safety tool to support the education of patients treated with oral antineoplastic agents. AB - OBJECTIVE: Oral antineoplastic agents (OAA) lead to new challenges in patient education, monitoring, medication errors, drug interactions, adverse events management, and adherence. The aim is to develop a structured guide supporting pharmacist interviews and onco-hematologic outpatients' education process and to identify the key points that a pharmacist should address in order to increase OAA safety and efficacy. METHODS: A literature review was performed and the recommended standards associated with OAA approved by ASCO and MASCC were analyzed. Additionally, a multidisciplinary team was formed to address the key points associated with OAA in clinical practice and to create a useful clinical guide. RESULTS: The multidisciplinary team defined the safety and efficacy key points during patient education and issued recommendations regarding the following items: dose, drug administration, interactions, adverse events, adherence, literacy, quality of life, storage, and handling. A guide was created as a check-list in support of the pharmacist clinical interview. Implications for clinical practice, including adverse events management, drug interactions management, and interventions on adherence were added. CONCLUSION: This article provides a consensus set of safety recommendations regarding OAA in clinical practice and a well-researched easily implementable support guide to standardize and guarantee quality pharmaceutical care of onco-hematologic outpatients. PMID- 26854364 TI - Carbohydrate-Catalyzed Enantioselective Alkene Diboration: Enhanced Reactivity of 1,2-Bonded Diboron Complexes. AB - Catalytic enantioselective diboration of alkenes is accomplished with readily available carbohydrate-derived catalysts. Mechanistic experiments suggest the intermediacy of 1,2-bonded diboronates. PMID- 26854365 TI - The characteristics of genetically related Pseudomonas aeruginosa from diverse sources and their interaction with human cell lines. AB - We investigated a collection of Pseudomonas aeruginosa strains from hospitalised patients (n = 20) and various environmental sources (n = 214) for their genetic relatedness; virulence properties; antibiotic resistance; and interaction with intestinal (Caco-2), renal (A-498), and lung (Calu-3) cell lines. Using RAPD-PCR, we found high diversity among the strains irrespective of their sources, with only 6 common (C) types containing strains from both a clinical and environmental source. Environmental strains belonging to these C-types showed greater adhesion to A-498 cells than did clinical strains (17 +/- 13 bacteria/cell versus 13 +/- 11 bacteria/cell; p < 0.001), whereas clinical strains showed significantly greater adhesion to Calu-3 and Caco-2 cells than did environmental strains (p < 0.001 for both). The virulence genes and antibiotic resistance profiles of the strains were similar; however, the prevalence of environmental strains carrying both exoS and exoU was significantly (p < 0.0368) higher than clinical strains. While all strains were resistant to ticarcillin and ticarcillin-clavulanic acid, resistance against aztreonam, gentamicin, amikacin, piperacillin, and ceftazidime varied among environmental and clinical strains. These results suggest that environmental strains of P. aeruginosa carry virulence properties similar to clinical strains, including adhesion to various human cell lines, with some strains showing a higher adhesion to specific cell lines, indicating they may have a better ability to cause infection in those sites under predisposing conditions of the host. PMID- 26854366 TI - Effect of miR-143-3p on C2C12 myoblast differentiation. AB - MicroRNAs are a class of 18-22 nucleotide non-coding RNAs that modulate gene expression by associating with the 3' untranslated regions of mRNAs. A large number of microRNAs are involved in the regulation of myoblast differentiation, many of which remain undiscovered. In this study, we found that miR-143-3p was upregulated during C2C12 myoblast differentiation and over-expression of miR-143 3p significantly inhibited the relative expression levels of MyoD, MyoG, myf5, and MyHC genes, especially in the later stages of differentiation. In addition, miR-143-3p inhibited expression of genes involved in the endogenous Wnt signaling pathway during C2C12 myoblast differentiation, including Wnt5a, LRP5, Axin2, and beta-catenin. These results indicate that miR-143-3p represents a new myogenic differentiation-associated microRNA that can inhibit C2C12 myoblast differentiation, especially in the later stages of differentiation. PMID- 26854367 TI - Preservation of three-dimensional anatomy in phosphatized fossil arthropods enriches evolutionary inference. AB - External and internal morphological characters of extant and fossil organisms are crucial to establishing their systematic position, ecological role and evolutionary trends. The lack of internal characters and soft-tissue preservation in many arthropod fossils, however, impedes comprehensive phylogenetic analyses and species descriptions according to taxonomic standards for Recent organisms. We found well-preserved three-dimensional anatomy in mineralized arthropods from Paleogene fissure fillings and demonstrate the value of these fossils by utilizing digitally reconstructed anatomical structure of a hister beetle. The new anatomical data facilitate a refinement of the species diagnosis and allowed us to reject a previous hypothesis of close phylogenetic relationship to an extant congeneric species. Our findings suggest that mineralized fossils, even those of macroscopically poor preservation, constitute a rich but yet largely unexploited source of anatomical data for fossil arthropods. PMID- 26854368 TI - Neurotoxic phospholipase A2 from rattlesnake as a new ligand and new regulator of prokaryotic receptor GLIC (proton-gated ion channel from G. violaceus). AB - Neurotoxic phospholipases A2 (sPLA2) from snake venoms interact with various protein targets with high specificity and potency. They regulate function of multiple receptors or channels essential to life processes including neuronal or neuromuscular chemoelectric signal transduction. These toxic sPLA2 exhibit high pharmacological potential and determination of PLA2-receptor binding sites represents challenging part in the receptor-channel biochemistry and pharmacology. To investigate the mechanism of interaction of neurotoxic PLA2 with its neuronal receptor at the molecular level, we used as a model crotoxin, a heterodimeric sPLA2 from rattlesnake venom and proton-gated ion channel GLIC, a bacterial homolog of pentameric ligand-gated ion channels. The three-dimensional structures of both partners, crotoxin and GLIC have been solved by X-ray crystallography and production of full-length pentameric GLIC (with ECD and TM domains) is well established. In the present study, for the first time, we demonstrated physical and functional interaction of full-length purified and solubilized GLIC with CB, (PLA2 subunit of crotoxin). We identified GLIC as a new protein target of CB and CB as a new ligand of GLIC, and showed that this non covalent interaction (PLA2-GLIC) involves the extracellular domain of GLIC. We also determined a novel function of CB as an inhibitor of proton-gated ion channel activity. In agreement with conformational changes observed upon formation of the complex, CB appears to be negative allosteric modulator (NAM) of GLIC. Finally, we proposed a possible stoichiometric model for CB - GLIC interaction based on analytical ultracentrifugation. PMID- 26854369 TI - Pathophysiological effects caused by the venom of the social wasp Synoeca surinama. AB - Envenomation by wasp stings is a public health preoccupation, and signals after stings have variable effects depending on the number of attacks and individual sensitivities. Even with the high rate of wasp sting cases, the study of phatophysiological effects of the envenomation is still very incipient. In this context, early and accurate assessment of this prognostic can aid in the reduction of the symptomatology and complete remission of the later symptoms. Then, the present study evaluated the toxicological effects caused by envenomation produced by Synoeca surinama, a wasp easily found in Neotropical regions. In vivo tests comprised the evaluation of LD50 (OECD 423), nociception, edema, myotoxic lesion and hemorrhage induction, in vitro tests were realized to evaluate hemolysis, contractile and coagulation alteration. The envenomation effects observed were dose- and time-dependent; the LD50 observed for S. surinama was 178 MUg/kg, approximately 17 times more lethal than that of the honeybee. Moreover, a potent algesic and oedema effect, and weak hemorrhagic signal were observed after injection of the venom wasp. Assays in vitro showed that this venom is able to prolong the clotting time of plasma and to increase creatine kinase levels. Our results demonstrated that this venom induced serious local and systemic effects in mammals and, so, to avoid permanent damage to the patient, health professionals should carefully investigate each accident. Moreover, due to its high occurrence in Neotropical regions, ecological management, particularly in areas with free access of children and elderly, should be performed. PMID- 26854370 TI - Human beta-defensin 1, a new animal toxin-like blocker of potassium channel. AB - The discovery of human beta-defensin 2 (hBD2), as a Kv1.3 channel inhibitor with the unique molecular mechanism and novel immune modulatory function, suggests that human beta-defensins are a novel class of channel ligands. Here, the function and mechanism of the human beta-defensin 1 (hBD1) binding to potassium channels was investigated. Based on the structural similarity between hBD1 and Kv1.3 channel-sensitive hBD2, hBD1 was found to selectively inhibit human and mouse Kv1.3 channels with IC50 values of 11.8 +/- 3.1 MUM and 13.2 +/- 4.0 MUM, respectively. Different from hBD2 modifying Kv1.3 channel activation and increasing activation time constant, hBD1 did not affect the activation feature of both human and mouse Kv1.3 channels. In comparison with hBD2 simultaneously interacting with the extracellular S1-S2 linker and pore region of Kv1.3 channel, the chimeric channel and mutagenesis experiments showed that hBD1 only bound to the extracellular pore region of Kv1.3 channel instead of extracellular S1-S2 linker or S3-S4 linker. Together, these findings enhance knowledge of hBD1 as a new immune-related Kv1.3 channel blocker and highlight the major functional differences between hBD1 and hBD2 to explore in future research. PMID- 26854371 TI - Whole genome analysis of an MDR Beijing/W strain of Mycobacterium tuberculosis with large genomic deletions associated with resistance to isoniazid. AB - Mycobacterium tuberculosis (M.tb) is one of the most prevalent bacterial pathogens in the world. With geographical wide spread and hypervirulence, Beijing/W family is the most successful M.tb lineage. China is a country of high tuberculosis (TB) and high multiple drug-resistant TB (MDR-TB) burden, and the Beijing/W family strains take the largest share of MDR strains. To study the genetic basis of Beijing/W family strains' virulence and drug resistance, we performed the whole genome sequencing of M.tb strain W146, a clinical Beijing/W genotype MDR isolated from Wuxi, Jiangsu province, China. Compared with genome sequence of M.tb strain H37Rv, we found that strain W146 lacks three large fragments and the missing of furA-katG operon confers isoniazid resistance. Besides the missing of furA-katG operon, strain W146 harbored almost all known drug resistance-associated mutations. Comparison analysis of single nucleotide polymorphisms (SNPs) and indels between strain W146 and Beijing/W genotype strains and non-Beijing/W genotype strains revealed that strain W146 possessed some unique mutations, which may be related to drug resistance, transmission and pathogenicity. These findings will help to understand the large sequence polymorphisms (LSPs) and the transmission and drug resistance related genetic characteristics of the Beijing/W genotype of M.tb. PMID- 26854372 TI - Expression, purification and characterization of the recombinant cysteine-rich antimicrobial peptide snakin-1 in Pichia pastoris. AB - Snakin-1 (SN-1) is a small cysteine-rich plant antimicrobial peptide with broad spectrum antimicrobial activity which was isolated from potato (Solanum tuberosum). Here, we carried out the expression of a recombinant SN-1 in the methylotrophic yeast Pichia pastoris, along with its purification and characterization. A DNA fragment encoding the mature SN-1 was cloned into pPIC9 vector and introduced into P. pastoris. A large amount of pure recombinant SN-1 (approximately 40 mg/1L culture) was obtained from a fed-batch fermentation culture after purification with a cation exchange column followed by RP-HPLC. The identity of the recombinant SN-1 was verified by MALDI-TOF MS, CD and (1)H NMR experiments. All these data strongly indicated that the recombinant SN-1 peptide had a folding with six disulfide bonds that was identical to the native SN-1. Our findings showed that SN-1 exhibited strong antimicrobial activity against test microorganisms and produced very weak hemolysis of mammalian erythrocytes. The mechanism of its antimicrobial action against Escherichia coli was investigated by both outer membrane permeability assay and cytoplasmic membrane depolarization assay. These assays demonstrated that SN-1 is a membrane-active antimicrobial peptide which can disrupt both outer and cytoplasmic membrane integrity. This is the first report on the recombinant expression and purification of a fully active SN-1 in P. pastoris. PMID- 26854373 TI - Causes of stillbirth in Turku, Finland, 2001-2011. AB - The objective of the study was to examine the causes of stillbirth in the district of Southwest Finland and to assess the importance of post-mortem examination, and the selection of a suitable classification system for classifying stillbirths. This study is a cohort study where the fetal autopsies were performed in the Department of Pathology at Turku University Hospital, Finland, 2001-2011. Stillbirths from singleton pregnancies at the gestational age of {greater than or equal to}24+0 weeks (if unknown, gestational weight {greater than or equal to}500g) (n=98) were selected. In addition, stillbirths from multiple gestations (n=6) were also analyzed. The causes of stillbirths were classified according to the Relevant Condition at Death (ReCoDe) classification system. Maternal risk factors and the role of fetal gestational age and weight for the causes of stillbirth were assessed. The most common causes of singleton stillbirth were lethal congenital anomalies, placental insufficiencies, and constricting loops and knots of the umbilical cord. The cause of singleton stillbirth could be determined for 78% of the cases, leaving 22% unclassified. There were no significant differences in the causes of stillbirth by gestational age or weight. Smoking may increase the incidence of placental abruption (p < 0.01). The most common causes of stillbirth in Turku, Finland are consistent with findings from other high-income countries. With careful post-mortem examination and ancillary studies it is possible to find the cause of stillbirth for most of the cases. Even if the stillbirth is left unexplained, many other harmful conditions can be excluded thus benefiting both the parents and the health care unit. PMID- 26854374 TI - Chemical modifications in the seed region of miRNAs 221/222 increase the silencing performances in gastrointestinal stromal tumor cells. AB - Most GastroIntestinal Stromal Tumors (GISTs) are characterized by KIT gene overexpression, which in turn is regulated by levels of microRNA 221 and microRNA 222. GISTs can also be distinguished by their miRNAs expression profile in which miRNAs 221/222 result reduced in comparison with GI normal tissues. In this paper, to restore normal miRNAs levels and to improve the silencing performances of miRNAs 221/222, new miRNA mimics in which guide strands are modified by Phosphorothioate (PS) and/or 2'-O-methyl RNA (2'-OMe) inside and outside the seed region, were synthesized and tested in GIST48 cells. We evaluated the positional effect of the chemical modifications on the miRNAs silencing activity, compared to natural and several commercial miRNA mimics. Our results show that chemically modified miRNAs 221/222 with alternating 2'-OMe-PS and natural nucleotides in the seed region are effective inhibitors of KIT gene expression and exhibit increased stability in rat plasma. Besides, their transfection in GIST 48 cells showed significant effects on different cellular processes in which KIT plays a functional role for tumor development (such as migration, cell proliferation, and apoptosis). Therefore, modified miRNAs 221/222 may provide an alternative therapeutic option for GIST treatment also aimed to overcome drug resistance concerns. PMID- 26854375 TI - Synthesis and screening of ursolic acid-benzylidine derivatives as potential anti cancer agents. AB - Ursolic acid present abundantly in plant kingdom is a well-known compound with various promising biological activities including, anti-cancer, anti inflammatory, hepatoprotective, antiallergic and anti-HIV properties. Herein, a library of ursolic acid-benzylidine derivatives have been designed and synthesized using Claisen Schmidt condensation of ursolic acid with various aromatic aldehydes in an attempt to develop potent antitumor agents. The compounds were evaluated against a panel of four human carcinoma cell lines including, A-549 (lung), MCF-7 (breast), HCT-116 (colon), THP-1 (leukemia) and a normal human epithelial cell line (FR-2). The results from MTT assay revealed that all the compounds displayed high level of antitumor activities compared with the triazole analogs (previously reported) and the parent ursolic acid. However, compound 3b, the most active derivative was subjected to mechanistic studies to understand the underlying mechanism. The results revealed that compound 3b induced apoptosis in HCT-116 cell lines, arrest cell cycle in the G1 phase, caused accumulation of cytochrome c in the cytosol and increased the expression levels of caspase-9 and caspase-3 proteins. Therefore, compound 3b induces apoptosis in HCT-116 cells through mitochondrial pathway. PMID- 26854376 TI - Non-symmetrical furan-amidines as novel leads for the treatment of cancer and malaria. AB - NRH:quinone oxidoreductase 2 enzyme (NQO2) is a potential therapeutic target in cancer and neurodegenerative diseases, with roles in either chemoprevention or chemotherapy. Here we report the design, synthesis and evaluation of non symmetrical furan-amidines and their analogues as novel selective NQO2 inhibitors with reduced adverse off-target effects, such as binding to DNA. A pathway for the synthesis of the non-symmetrical furan-amidines was established from the corresponding 1,4-diketones. The synthesized non-symmetrical furan-amidines and their analogues showed potent NQO2 inhibition activity with nano-molar IC50 values. The most active compounds were non-symmetrical furan-amidines with meta- and para-nitro substitution on the aromatic ring, with IC50 values of 15 nM. In contrast to the symmetric furan-amidines, which showed potent intercalation in the minor grooves of DNA, the synthesized non-symmetrical furan-amidines showed no affinity towards DNA, as demonstrated by DNA melting temperature experiments. In addition, Plasmodium parasites, which possess their own quinone oxidoreductase PfNDH2, were inhibited by the non-symmetrical furan-amidines, the most active possessing a para-fluoro substituent (IC50 9.6 nM). The high NQO2 inhibition activity and nanomolar antimalarial effect of some of these analogues suggest the lead compounds are worthy of further development and optimization as potential drugs for novel anti-cancer and antimalarial strategies. PMID- 26854377 TI - Phthalimido-thiazoles as building blocks and their effects on the growth and morphology of Trypanosoma cruzi. AB - Chagas disease is a parasitic infection caused by protozoan Trypanosoma cruzi that affects approximately 6-7 million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases; however, its efficacy during the symptomatic chronic phase is controversial. The present work reports the synthesis and anti-T. cruzi activities of a novel series of phthalimido-thiazoles. Some of these compounds showed potent inhibition of the trypomastigote form of the parasite at low cytotoxicity concentrations in spleen cells, and the resulting structure-activity relationships are discussed. We also showed that phthalimido-thiazoles induced ultrastructural alterations on morphology, flagellum shortening, chromatin condensation, mitochondria swelling, reservosomes alterations and endoplasmic reticulum dilation. Together, these data revealed, for the first time, a novel series of phthalimido-thiazoles-structure based compounds with potential effects against T. cruzi and lead-like characteristics against Chagas disease. PMID- 26854378 TI - Glucose-functionalized amino-OPEs as biocompatible photosensitizers in PDT. AB - Photodynamic therapy (PDT) is a minimally invasive procedure that can provide a selective eradication of neoplastic diseases by the combined effect of a photosensitizer, light and oxygen. New amino oligo(phenylene-ethynylene)s (OPEs), bearing hydrophilic glucoside terminations, have been prepared, characterized and tested as photosensitizers in PDT. The effectiveness of these compounds in combination with UVA light has been checked on two tumor cell lines (HEp-2 and HeLa cells, derived from a larynx carcinoma and a cervical carcinoma, respectively). The compounds triggered a mitotic blockage that led to the cell death, being the effect active up to 3 MUm concentration. The photophysical properties of OPEs, such as high quantum yield, stability, singlet oxygen production, biocompatibility, easy cell-internalization and very good response even at low concentration, make them promising photosensitizers in the application of PDT. PMID- 26854379 TI - Synthesis and biology of ring-modified l-Histidine containing thyrotropin releasing hormone (TRH) analogues. AB - Thyrotropin-releasing hormone (TRH) analogues bearing halogen groups (Cl, Br and I) at the C-2 and/or C-5 position, and the alkyl group (CH3, C2H5, C3H7, CH2C6H5) at the N-1 position of the imidazole ring of the central histidine residue were synthesized and evaluated for the receptor binding, calcium mobilization (FLIPR), and IP-1 assay at the HEK mTRHR1 and HEK mTRHR2 expressing cell lines. The most promising analogue 7k showed 925-fold selectivity for HEK mTRH-R2 receptor subtype in the IP-1 assay, 272-fold selectivity for HEK mTRH-R2 receptor subtype in the FLIPR assay, and 21-fold receptor binding specificity at HEK TRH-R2 receptor subtype. The peptide 7k was evaluated in vitro in a brain membrane competitive binding assay, and for stability analysis in the presence of TRH-DE, in vivo. The analogue 7k showed decrease in the sleeping time by more than 76% in a pentobarbital-induced sleeping assay, and showed comparatively less elevation in the TSH level in the blood, in vivo. The computational homology modeling of TRH-R1 and TRH-R2 and docking study with the most potent peptide 7k provide impetus to design CNS specific TRH analogues. PMID- 26854380 TI - Modification of the length and structure of the linker of N(6)-benzyladenosine modulates its selective antiviral activity against enterovirus 71. AB - Very recently, we demonstrated that N(6)-isopentenyladenosine, a cytokinin nucleoside, exerts a potent and selective antiviral effect on the replication of human enterovirus 71. The present study is devoted to the structure optimization of another natural compound: N(6)-benzyladenosine. We mainly focused on the exploration of the size and nature of the linker between the adenine and the phenyl ring, as well as on the necessity of the D-ribose residue. More than 30 analogues of N(6)-benzyladenosine were prepared and their antiviral properties were evaluated. Two main methodologies were used for preparation: N(6)-acetyl 2',3',5'-tri-O-acetyladenosine can be regioselectively alkylated either by alkyl halides under base promoted conditions or by alcohols in Mitsunobu reactions. After deacylation with 4 M PrNH2 in MeOH at room temperature for one day, the desired products were obtained in overall high yields. Analysis of the structure activity relationship clearly shows that the optimal size of the linker is limited to 2 or 3 atoms (compounds 4-7). 2'-Deoxyadenosine derivatives did not elicit any inhibitory or cytotoxic effect, while 5'-deoxynucleosides still induced some cell protective antiviral activity. Based on these observations, it can be hypothesized that there may be another mechanism that is at the base of the antiviral activity of these compounds against enterovirus 71 besides a possible 5'-triphosphorylation followed by a putative inhibitory effect on RNA synthesis. PMID- 26854381 TI - Dihydro-beta-agarofuran sesquiterpenes from celastraceae species as anti-tumour promoting agents: Structure-activity relationship. AB - Inhibition of tumour promotion in multistage chemical carcinogenesis is considered a promising strategy for cancer chemoprevention. In an ongoing investigation of bioactive secondary metabolites from Celastraceae species, five new dihydro-beta-agarofuran sesquiterpenes (1-5), named Chiapens A-E, and seventeen known ones, were isolated from Maytenus chiapensis. Their structures were elucidated by extensive NMR spectroscopic and mass spectrometric techniques, and their absolute configurations were determined by circular dichroism studies, chemical correlations and biogenic means. The isolated compounds, along with twenty known sesquiterpenes, previously isolated from Zinowiewia costaricensis, have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorpol-13-acetate (TPA). Thirty three compounds from this series showed stronger effects than that of beta carotene, the reference inhibitor. The structure-activity relationship (SAR) analysis revealed that the type of substituent, in particular at the C-1 position of the sesquiterpene scaffold, was able to modulate the anti-tumour promoting activity. Compounds 3, 6, and 33 showed significant effects in an in vivo two stage mouse-skin carcinogenesis model. PMID- 26854382 TI - Novel drug targets for idiopathic pulmonary fibrosis. AB - Idiopathic Pulmonary Fibrosis (IPF) is a progressive, fatal lung disorder of unknown cause with a highly variable and unpredictable clinical course. The advances made in deciphering IPF pathobiology over the last decades have led to the approval of two anti-fibrotic molecules, pirfenidone and nintedanib, that showed to be effective in significantly reducing the rate of progression of the disease. Such pharmacological breakthroughs represent a dramatic change in the management of these patients and are reflected in updated international guidelines. However, the need to find a cure for this devastating disease remains unmet and the development of novel therapeutic agents remains hurdled by several factors. Here, we review the latest insights into therapeutic approaches for IPF and the available evidence for the most promising novel compounds currently under development, and discuss the challenges and evolution of IPF clinical research over the next few years. PMID- 26854384 TI - Beam configuration selection for robust intensity-modulated proton therapy in cervical cancer using Pareto front comparison. AB - The Pareto front reflects the optimal trade-offs between conflicting objectives and can be used to quantify the effect of different beam configurations on plan robustness and dose-volume histogram parameters. Therefore, our aim was to develop and implement a method to automatically approach the Pareto front in robust intensity-modulated proton therapy (IMPT) planning. Additionally, clinically relevant Pareto fronts based on different beam configurations will be derived and compared to enable beam configuration selection in cervical cancer proton therapy. A method to iteratively approach the Pareto front by automatically generating robustly optimized IMPT plans was developed. To verify plan quality, IMPT plans were evaluated on robustness by simulating range and position errors and recalculating the dose. For five retrospectively selected cervical cancer patients, this method was applied for IMPT plans with three different beam configurations using two, three and four beams. 3D Pareto fronts were optimized on target coverage (CTV D(99%)) and OAR doses (rectum V30Gy; bladder V40Gy). Per patient, proportions of non-approved IMPT plans were determined and differences between patient-specific Pareto fronts were quantified in terms of CTV D(99%), rectum V(30Gy) and bladder V(40Gy) to perform beam configuration selection. Per patient and beam configuration, Pareto fronts were successfully sampled based on 200 IMPT plans of which on average 29% were non approved plans. In all patients, IMPT plans based on the 2-beam set-up were completely dominated by plans with the 3-beam and 4-beam configuration. Compared to the 3-beam set-up, the 4-beam set-up increased the median CTV D(99%) on average by 0.2 Gy and decreased the median rectum V(30Gy) and median bladder V(40Gy) on average by 3.6% and 1.3%, respectively. This study demonstrates a method to automatically derive Pareto fronts in robust IMPT planning. For all patients, the defined four-beam configuration was found optimal in terms of plan robustness, target coverage and OAR sparing. PMID- 26854383 TI - Effect of secondary anchor amino acid substitutions on the immunogenic properties of an HLA-A*0201-restricted T cell epitope derived from the Trypanosoma cruzi KMP 11 protein. AB - The TcTLE peptide (TLEEFSAKL) is a CD8(+) T cell HLA-A*0201-restricted epitope derived from the Trypanosoma cruzi KMP-11 protein that is efficiently processed, presented and recognized by CD8(+) T cells from chagasic patients. Since the immunogenic properties of wild-type epitopes may be enhanced by suitable substitutions in secondary anchor residues, we have studied the effect of introducing specific mutations at position 3, 6 and 7 of the TcTLE peptide. Mutations (E3L, S6V and A7F) were chosen on the basis of in silico predictions and in vitro assays were performed to determine the TcTLE-modified peptide binding capacity to the HLA-A*0201 molecule. In addition, the functional activity of peptide-specific CD8(+) T cells in HLA-A2(+) chagasic patients was also interrogated. In contrast to bioinformatics predictions, the TcTLE-modified peptide was found to have lower binding affinity and stability than the original peptide. Nevertheless, CD8(+) T cells from chronic chagasic patients recognized the TcTLE-modified peptide producing TNF-alpha and INF-gamma and expressing CD107a/b, though in less extension than the response triggered by the original peptide. Overall, although the amino acids at positions 3, 6 and 7 of TcTLE are critical for the peptide affinity, they have a limited effect on the immunogenic properties of the TcTLE epitope. PMID- 26854385 TI - Survey of the Presence of Toxocara spp. Eggs in Dog Feces in Tartu, Estonia. AB - Several zoonotic pathogens are shed in the feces of infected animals. If they are allowed to contaminate the environment, they cause a public health concern. In this study, we investigated the presence of Toxocara spp. eggs in dog feces in the urban area of Tartu, Estonia. Samples were collected by veterinary students in 2014 and examined using a modified concentration-flotation technique. Toxocara spp. eggs were detected by microscopy in 4 (1.7%) out of 234 canine fecal samples. PMID- 26854386 TI - Analytical evaluation of the epoc(r) point-of-care blood analysis system in cardiopulmonary bypass patients. AB - OBJECTIVES: The aim of this study was to evaluate the analytical performance of the new epoc(r) point-of-care blood analysis system in cardiopulmonary bypass patients. DESIGN AND METHODS: The precision study was conducted on 3 epoc(r) blood analysis systems using 5 levels of quality control materials twice per day for 5days. The blood specimen was collected in blood gas syringes from 40 cardiac perfusion patients for the comparison study on epoc(r) (all 3meters), Instrumentation Laboratory GEM4000, Abbott iSTAT, Nova CCX, and Roche Accu-Chek Inform II and Performa glucose meters. RESULTS: The epoc(r) blood analysis systems demonstrated clinically acceptable precision for all analytes (from 0.07%, 0.07%, and 0.13% for pH7.6, 7.4, and 7.0 levels; to 3.87%, 3.74%, and 7.56% for pO2 197, 103, and 56mmHg levels). Comparison studies yielded a correlation coefficient R from 0.9201 (sodium) to 0.9969 (pO2) with the GEM4000; from 0.9071 (sodium) to 0.9965 (potassium) with the iSTAT; from 0.8793 (sodium) to 0.9957 (pO2) with the CCX, and 0.9850 and 0.9904 with Roche Inform II and Performa meters respectively. Average biases for all analytes were within the total allowable error limits. CONCLUSION: The epoc(r) blood analysis system is acceptable for point-of-care testing in the cardiovascular surgery setting. PMID- 26854387 TI - Fish-eye disease: Another under-recognized cause of familial corneal opacification. PMID- 26854388 TI - Mesenchymal cells condensation-inducible mesh scaffolds for cartilage tissue engineering. AB - Mesenchymal cells condensation is crucial in chondrogenic development. However current tissue-engineered scaffolds for chondrogenesis pay little attention to this phenomenon. In this study, we fabricate poly(l-lactide-co-glycolide) (PLGA)/poly(l-lactide) (PLLA) microfiber scaffolds and coat them with human fibroblast-derived matrix (hFDM) that is a decellularized extracellular matrix (ECM) obtained from in vitro cultured human lung fibroblasts (WI-38). Those scaffolds were then conjugated with heparin via EDC chemistry and subsequently immobilized with transforming growth factor (TGF)-beta1. The amount of TGF-beta1 was quantitatively measured and the release profile showed a continuous release of TGF-beta1 for 4 weeks. Human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) were seeded in four different scaffolds; control, fibronectin (FN)-coated, hFDM-coated, hFDM/TGF-beta1 and subjected to chondrogenic differentiation in vitro for up to 28 days. Both hFDM and hFDM/TGF-beta1 groups exhibited significantly more synthesis of glycosaminoglycan (GAG) and much better upregulation of chondrogenic markers expression. Interestingly, MSCs condensation that led to cell aggregates was clearly observed with time in the two hFDM-coated groups and the quantitative difference was obvious compared to the control and FN group. A mechanistic study in gene and protein level indicated that focal adhesion kinase (FAK) was involved at the early stage of cell adhesion and cell cell contact-related markers, N-cadherin and neural cell adhesion molecule (NCAM), were highly up-regulated at later time point. In addition histological analysis proved that hFDM/TGF-beta1 group was the most effective in forming neocartilage tissue in a rabbit articular cartilage defect model. Taken together, this study demonstrates not only the positive effect of hFDM on chondrogenesis of MSCs and cartilage repair but also provides an important insight toward the significance of in vitro mesenchymal condensation on chondrogenic development of MSCs. PMID- 26854389 TI - pH-activated size reduction of large compound nanoparticles for in vivo nucleus targeted drug delivery. AB - Nucleus-targeted drug delivery is a promising strategy for anticancer therapy, but in vivo nucleus-targeted drug delivery has been challenging. Limited by the channel size of the nucleopore, vehicles that enter the nucleus via the nucleopore actively should be small and decorated with nuclear localization signal (NLS). However, the small vehicle size may promote leakage of vehicles into normal tissues, and the positively-charged NLS can lead to strong non specific interactions in vivo. In the present study, we demonstrate an in vivo nucleus-targeted drug delivery using large compound nanoparticles with detachable PEG shell. The nanoparticles are composed of PEG-benzoic imine-oligo-l lysine/iridium(III) metallodrug complex and formed in a kinetically-controlled fashion. Under physiological conditions (pH 7.4), the nanoparticles are large (ca. 150 nm) and protected by an inert PEG shell. When internalized into intracellular acidic endo/lysosomes of cancer cells, the nanoparticles dissociate into smaller ones (ca. 40 nm) and the PEG chains detach due to the cleavage of the benzoic imine bond at low pH. The small nanoparticles, with exposure of the oligo-l-lysine after the detachment of the PEG shield, then translocate into the nucleus via the nucleopore due to the small size and nuclear localization ability of the oligo-l-lysine. Importantly, the small particles could significantly release the contained drug into the nucleus, leading to ca. 20-fold higher cytotoxicity compared to the native drug in vitro. Further in vivo application of the nucleus-targeting nano-system in a nude-mice model showed significant tumor inhibition and remarkable life-span elongation. PMID- 26854390 TI - The AGMA1 poly(amidoamine) inhibits the infectivity of herpes simplex virus in cell lines, in human cervicovaginal histocultures, and in vaginally infected mice. AB - The development of topical microbicides is a valid approach to protect the genital mucosa from sexually transmitted infections that cannot be contained with effective vaccination, like HSV and HIV infections. A suitable target of microbicides is the interaction between viral proteins and cell surface heparan sulfate proteoglycans (HSPGs). AGMA1 is a prevailingly cationic agmatine containing polyamidoamine polymer previously shown to inhibit HSPGs dependent viruses, including HSV-1, HSV-2, and HPV-16. The aim of this study was to elucidate the mechanism of action of AGMA1 against HSV infection and assess its antiviral efficacy and biocompatibility in preclinical models. The results show AGMA1 to be a non-toxic inhibitor of HSV infectivity in cell cultures and human cervicovaginal histocultures. Moreover, it significantly reduced the burden of infection of HSV-2 genital infection in mice. The investigation of the mechanism of action revealed that AGMA1 reduces cells susceptibility to virus infection by binding to cell surface HSPGs thereby preventing HSV attachment. This study indicates that AGMA1 is a promising candidate for the development of a topical microbicide to prevent sexually transmitted HSV infections. PMID- 26854391 TI - Infrared-active quadruple contrast FePt nanoparticles for multiple scale molecular imaging. AB - A single nanomaterial with multiple imaging contrasts and functions is highly desired for multiscale theragnosis. Herein, we demonstrate single 1-1.9 MUm infrared-active FePt alloy nanoparticles (FePt NPs) offering unprecedented four contrast-in-one molecular imaging - computed tomography (CT), magnetic resonance imaging (MRI), photoacoustic (PA) imaging, and high-order multiphoton luminescence (HOMPL) microscopy. The PA response of FePt NPs outperforms that of infrared-active gold nanorods by 3- to 5.6-fold under identical excitation fluence and particle concentrations. HOMPL (680 nm) of an isolated FePt NP renders spatial full-width-at-half-maximum values of 432 nm and 300 nm beyond the optical diffraction limit for 1230-nm and 920-nm excitation, respectively. The in vivo targeting function was successfully visualized using HOMPL, PA imaging, CT, and MRI, thereby validating FePt as a single nanomaterial system covering up to four types (Optical/PA/CT/MRI) of molecular imaging contrast, ranging from the microscopic level to whole-body scale investigation. PMID- 26854393 TI - Carboxyl- and amino-functionalized polystyrene nanoparticles differentially affect the polarization profile of M1 and M2 macrophage subsets. AB - Macrophages are key regulators of innate and adaptive immune responses. Exposure to microenvironmental stimuli determines their polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. M1 exhibit high expression of proinflammatory TNF-alpha and IL-1beta, and M2 promote tissue repair, but likewise support tumor growth and cause immune suppression by expressing IL-10. Thus, the M1/M2 balance critically determines tissue homeostasis. By using carboxyl- (PS-COOH) and amino-functionalized (PS-NH2) polystyrene nanoparticles, the effects of surface decoration on the polarization of human macrophages were investigated. The nanoparticles did not compromise macrophage viability nor did they affect the expression of the M1 markers CD86, NOS2, TNF-alpha, and IL-1beta. By contrast, in M2, both nanoparticles impaired expression of scavenger receptor CD163 and CD200R, and the release of IL-10. PS-NH2 also inhibited phagocytosis of Escherichia coli by both, M1 and M2. PS-COOH did not impair phagocytosis by M2, but increased protein mass in M1 and M2, TGF-beta1 release by M1, and ATP levels in M2. Thus, nanoparticles skew the M2 macrophage polarization without affecting M1 markers. Given the critical role of the M1 and M2 polarization for the immunological balance in patients with cancer or chronic inflammation, functionalized nanoparticles might serve as tools for reprogramming the M1/M2 polarization. PMID- 26854392 TI - The synthesis and coupling of photoreactive collagen-based peptides to restore integrin reactivity to an inert substrate, chemically-crosslinked collagen. AB - Collagen is frequently advocated as a scaffold for use in regenerative medicine. Increasing the mechanical stability of a collagen scaffold is widely achieved by cross-linking using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N hydroxysuccinimide (NHS). However, this treatment consumes the carboxylate containing amino acid sidechains that are crucial for recognition by the cell surface integrins, abolishing cell adhesion. Here, we restore cell reactivity to a cross-linked type I collagen film by covalently linking synthetic triple helical peptides (THPs), mimicking the structure of collagen. These THPs are ligands containing an active cell-recognition motif, GFOGER, a high-affinity binding site for the collagen-binding integrins. We end-stapled peptide strands containing GFOGER by coupling a short diglutamate-containing peptide to their N terminus, improving the thermal stability of the resulting THP. A photoreactive Diazirine group was grafted onto the end-stapled THP to allow covalent linkage to the collagen film upon UV activation. Such GFOGER-derivatized collagen films showed restored affinity for the ligand-binding I domain of integrin alpha2beta1, and increased integrin-dependent cell attachment and spreading of HT1080 and Rugli cell lines, expressing integrins alpha2beta1 and alpha1beta1, respectively. The method we describe has wide application, beyond collagen films or scaffolds, since the photoreactive diazirine will react with many organic carbon skeletons. PMID- 26854394 TI - Magnetic nanocomposite scaffolds combined with static magnetic field in the stimulation of osteoblastic differentiation and bone formation. AB - Magnetism has recently been implicated to play significant roles in the regulation of cell responses. Allowing cells to experience a magnetic field applied externally or scaffolding them in a material with intrinsic magnetic properties has been a possible way of utilizing magnetism. Here we aim to investigate the combined effects of the external static magnetic field (SMF) with magnetic nanocomposite scaffold made of polycaprolactone/magnetic nanoparticles on the osteoblastic functions and bone formation. The SMF synergized with the magnetic scaffolds in the osteoblastic differentiation of primary mouse calvarium osteoblasts, including the expression of bone-associated genes (Runx2 and Osterix) and alkaline phosphatase activity. The synergism was demonstrated in the activation of integrin signaling pathways, such as focal adhesion kinase, paxillin, RhoA, mitogen-activated protein kinase, and nuclear factor-kappaB, as well as in the up-regulation of bone morphogenetic protein-2 and phosphorylation of Smad1/5/8. Furthermore, the SMF/magnetic scaffold-stimulated osteoblasts promoted the angiogenic responses of endothelial cells, including the expression of vascular endothelial growth factor and angiogenin-1 genes and the formation of capillary tubes. When the magnetic scaffolds were implanted in mouse calvarium defects, the application of SMF significantly enhanced the new bone formation at 6 weeks, as revealed by the histological and micro-computed tomographic analyses. Current findings suggest that the combinatory application of external (SMF) and internal (scaffold) magnetism can be a promising tool to regenerative engineering of bone. PMID- 26854395 TI - Nausea in pregnancy: attitudes among pregnant women and general practitioners on treatment and pregnancy care. AB - OBJECTIVE: Nausea and vomiting during pregnancy (NVP) is very common, and may have great impact on a woman's life. The aim of this study was to explore thoughts and attitudes among Norwegian pregnant women and GPs on treatment of NVP and pregnancy care. DESIGN: Focus-group study. SETTING AND SUBJECTS: Separate focus-group discussions were conducted with pregnant women and GPs. RESULTS: Two focus-group discussions were conducted with pregnant women and two with GPs. The GPs thought it was important to normalize NVP symptoms. However, the women felt their distress due to NVP was trivialized by the GPs. The women were sceptical towards the use of medicines while pregnant, and avoidance was sought despite being ill. The GPs appeared uncertain with respect to medical treatment of NVP, which was stated to be considered only after progression to quite severe symptoms. Sick leave seemed to be an important part of the treatment regime applied by the GPs. The women had good experiences with graded sick leave. CONCLUSION: This Norwegian study identifies attitudes among GPs and pregnant women that may act as obstacles to appropriate care for women with NVP. The pregnant women and the GPs seemed to talk at cross-purposes; GPs' normalization of the symptoms made the women feel that their distress due to NVP was trivialized by the GPs. Our results indicate that pregnant women with NVP requiring medical treatment probably need comprehensive and reassuring information about treatment options before considering using any medicines. KEY POINTS: Nausea and vomiting during pregnancy (NVP) is very common, and considered to be of clinical significance for 35% of women. While the GPs agreed on the importance of normalizing the symptoms, the women felt their distress was trivialized, and missed being properly evaluated. Both the GPs and the women showed a reluctant attitude to medical treatment of NVP. The GPs gave the impression of considering medical treatment only after progression of symptoms to becoming quite severe. PMID- 26854396 TI - Automated chair-training of rhesus macaques. AB - BACKGROUND: Neuroscience research on non-human primates usually requires the animals to sit in a chair. To do this, typically monkeys are fitted with collars and trained to enter the chairs using either a pole, leash and jump cage. Animals may initially show resistance and risk injury. We have developed an automated chair-training method that minimizes restraints to ease the animals into their chairs. NEW METHOD: We developed a method to automatically train animals to enter a primate chair and stick out their heads for neckplate placement. To do this, we fitted the chairs with Arduino microcontrollers coupled to a water-reward system and touch- and proximity sensors. RESULTS AND COMPARISON WITH EXISTING METHODS: We found that the animals responded well to the chair, partially entering the chair within hours, sitting inside the chair within days and allowing us to manually introduce a door and neck plate, all within 14-21 sessions. Although each session could last many hours, automation meant that actual training person hours could be as little as half an hour per day. The biggest advantage was that animals showed little resistance to entering the chair, compared to monkeys trained by leash pulling. CONCLUSIONS: This automated chair-training method can take longer than the standard collar-and-leash approach, but multiple macaques can be trained in parallel with fewer person-hours. It is also a promising method for animal-use refinement and in our case, it was the only effective training approach for an animal suffering from a behavioral pathology. PMID- 26854397 TI - A flow cytometric approach to analyzing mature and progenitor endothelial cells following traumatic brain injury. AB - BACKGROUND: Traumatic brain injury (TBI) continues to be a major source of death and disability worldwide, and one of the earliest and most profound deficits comes from vascular damage and breakdown of the blood-brain barrier (BBB). Cerebral vascular endothelial cells (cvECs) and endothelial progenitor cells (EPCs) have been shown to play essential roles in vessel repair and BBB stability, although their individual contributions remain poorly defined. NEW METHOD: We employ TruCount beads with flow cytometry to precisely quantify cvECs, EPCs, and peripheral leukocytes in the murine cortex after controlled cortical impact (CCI) injury. RESULTS: We found a significant reduction in the number of cvECs at 3 days post-injury (dpi), whereas the EPCs and invading peripheral leukocytes were significantly increased compared with sham controls. Proliferation studies demonstrate that both cvECs and EPCs are undergoing cell expansion in the first week post-injury. Furthermore, analysis of protein expression using mean fluorescence intensity found increases in PECAM-1, VEGFR-2, and VE-Cadherin expression per cell at 3 dpi, which is consistent with western blot analysis. COMPARISON WITH EXISTING METHODS: Classic methods of cell analysis, such as histological cell counts, in the traumatic injured brain are labor intensive, time-consuming, and potentially biased; whereas flow cytometry provides an efficient, non-biased approach to simultaneously quantify multiple cell types. However, conventional flow cytometry that employs capped events can provide misleading results in CNS injured tissues. CONCLUSIONS: We demonstrate that TruCount quantification using flow cytometry is a powerful tool for quantifying mature and progenitor endothelial cell changes after TBI. PMID- 26854398 TI - A Bayesian nonparametric approach for uncovering rat hippocampal population codes during spatial navigation. AB - BACKGROUND: Rodent hippocampal population codes represent important spatial information about the environment during navigation. Computational methods have been developed to uncover the neural representation of spatial topology embedded in rodent hippocampal ensemble spike activity. NEW METHOD: We extend our previous work and propose a novel Bayesian nonparametric approach to infer rat hippocampal population codes during spatial navigation. To tackle the model selection problem, we leverage a Bayesian nonparametric model. Specifically, we apply a hierarchical Dirichlet process-hidden Markov model (HDP-HMM) using two Bayesian inference methods, one based on Markov chain Monte Carlo (MCMC) and the other based on variational Bayes (VB). RESULTS: The effectiveness of our Bayesian approaches is demonstrated on recordings from a freely behaving rat navigating in an open field environment. COMPARISON WITH EXISTING METHODS: The HDP-HMM outperforms the finite-state HMM in both simulated and experimental data. For HPD HMM, the MCMC-based inference with Hamiltonian Monte Carlo (HMC) hyperparameter sampling is flexible and efficient, and outperforms VB and MCMC approaches with hyperparameters set by empirical Bayes. CONCLUSION: The Bayesian nonparametric HDP-HMM method can efficiently perform model selection and identify model parameters, which can used for modeling latent-state neuronal population dynamics. PMID- 26854399 TI - Cobblestone fallopian tubes on hysterosalpingogram followed by bilateral tubal abscesses and sepsis. PMID- 26854400 TI - Targeting FcgammaRs to treat antibody-dependent autoimmunity. AB - Self-reactive antibodies represent a significant force in autoimmune disease induction. In antibody-dependent autoimmune syndromes such as immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE), myasthenia gravis and rheumatoid arthritis (RA), autoantibodies exert their inflammatory effect through FcgammaRs, a well-established class of cell surface receptors that interact with the Fc domain of IgG. Down-regulating FcgammaR functionality presents an attractive strategy to treat antibody-dependent autoimmune diseases. Various approaches, including nonspecific blocking of the IgG binding site as well as specific targeting using antagonistic monoclonal antibodies, have been explored to modulate the interaction between the Fc portion of IgG and FcgammaRs. The exquisite specificity and favorable pharmacokinetics of IgG make monoclonal antibodies a preferred choice. Indeed, the first antagonistic monoclonal antibody against the human FcgammaRIIIA had shown efficacy in refractory ITP patients; however, the practicality of using anti-FcgammaRIII antibody as a therapeutic was hindered by its associated adverse events, a phenomenon recapitulated in animal models. In this review, we discuss the role of FcgammaRs in autoimmune diseases, and focus on a novel monovalent approach to target FcgammaRs to resolve antibody mediated autoimmunity. PMID- 26854401 TI - Understanding autoimmunity: The ion channel perspective. AB - Ion channels are integral membrane proteins that orchestrate the passage of ions across the cell membrane and thus regulate various key physiological processes of the living system. The stringently regulated expression and function of these channels hold a pivotal role in the development and execution of various cellular functions. Malfunction of these channels results in debilitating diseases collectively termed channelopathies. In this review, we highlight the role of these proteins in the immune system with special emphasis on the development of autoimmunity. The role of ion channels in various autoimmune diseases is also listed out. This comprehensive review summarizes the ion channels that could be used as molecular targets in the development of new therapeutics against autoimmune disorders. PMID- 26854403 TI - Influence of microalgal N and P composition on wastewater nutrient remediation. AB - Microalgae have demonstrated the ability to remediate wastewater nutrients efficiently, with methods to further enhance performance through species selection and biomass concentration. This work evaluates a freshwater species remediation characteristics through analysis of internal biomass N:P (nitrogen:phosphorus) and presents a relationship between composition and nutrient uptake ability to assist in species selection. Findings are then translated to an optimal biomass concentration, achieved through immobilisation enabling biomass intensification by modifying bead concentration, for wastewaters of differing nutrient concentrations at hydraulic retention times (HRT) from 3 h to 10 d. A HRT <20 h was found suitable for the remediation of secondary effluent by immobilised Scenedesmus obliquus and Chlorella vulgaris at bead concentrations as low as 3.2 and 4.4 bead.mL(-1). Increasing bead concentrations were required for shorter HRTs with 3 h possible at influent concentrations <5 mgP L(-1). PMID- 26854402 TI - Role of chaperone-mediated autophagy in metabolism. AB - Different types of autophagy coexist in most mammalian cells, and each of them fulfills very specific tasks in intracellular degradation. Some of these autophagic pathways contribute to cellular metabolism by directly hydrolyzing intracellular lipid stores and glycogen. Chaperone-mediated autophagy (CMA), in contrast, is a selective form of autophagy that can only target proteins for lysosomal degradation. Consequently, it was expected that the only possible contribution of this pathway to cellular metabolism would be by providing free amino acids resulting from protein breakdown. However, recent studies have demonstrated that disturbance in CMA leads to important alterations in glucose and lipid metabolism and in overall organism energetics. Here, we describe the unique mechanisms by which CMA contributes to the regulation of cellular metabolism and discuss the possible implications of these previously unknown functions of CMA for the pathogenesis of common metabolic diseases. PMID- 26854404 TI - Perceived distance and obesity: It's what you weigh, not what you think. AB - Action abilities are constrained by physical body size and characteristics, which, according to the action-specific account of perception, should influence perceived space. We examined whether physical body size or beliefs about body size affect distance perception by taking advantage of naturally-occurring dissociations typical in people who are obese but believe themselves to weigh less. Normal weight, overweight, and obese individuals made verbal distance estimates. We also collected measures of beliefs about body size and measures of physical body size. Individuals who weighed more than others estimated distances to be farther. Furthermore, physical body weight influenced perceived distance but beliefs about body size did not. The results illustrate that whereas perception is influenced by physical characteristics, it is not influenced by beliefs. The results also have implications for perception as a contributing factor for lifestyle choices: people who weigh more than others may choose to perform less physically demanding actions not as a result of how they perceive their bodies, but as a result of how they perceive the environment. PMID- 26854405 TI - Priming effect in indicative and subjunctive exceptive conditionals. AB - We report the results of three experiments that examine the mental representations underlying the comprehension stages of negative exceptive conditionals using subjunctive mood ('B a menos que A', 'B a no ser que A'; 'B excepto que A'='B unless A') and indicative mood ('B excepto si A' and 'B salvo si A'='B except if A'). The mental representations during the comprehension stage were analyzed using a priming methodology. All experiments showed that participants read the true possibility 'not-B & A' faster when it was primed by exceptive conditionals requiring the subjunctive mood than when it was primed by exceptive conditionals requiring the indicative mood; other possibilities ('B & A', 'B & not-A', 'not-B & not-A') were primed equally by both connectives. The experiments showed that (a) when people understand negative exceptive conditionals using the subjunctive mood, such as 'B a menos que A'/'B a no ser que A'/'B excepto que A', they access the true possibilities 'not-B & A' and 'B & not-A', and (b) when they understand negative exceptive conditionals using the indicative mood, such as 'B excepto si A'/'B salvo si A', they access 'B & not A', but not 'not-B & A'. We discuss the implications of this for current theories of reasoning. PMID- 26854406 TI - Charge transfer based "turn-on" chemosensor for Zn2+ ion recognition using new triaryl pyrazoline derivative. AB - The fluoroionophore PY serves as a selective and fluorimetric chemosensor for Zn(2+) based on charge transfer (CT). A mechanism for the binding mode was proposed based on fluorescence changes, NMR experiments and theoretical calculations. The 1:1 stoichiometry between Zn(2+) and the sensor was deduced from Job's plot. The addition of EDTA quenches the fluorescence of PY.Zn(2+) complex offers PY as a reversible chemosensor. PMID- 26854407 TI - Effects of salinity on the photosynthetic apparatus of two Paulownia lines. AB - The effects of soil salinity on the functional activity of photosynthetic apparatus and pigment composition of two Paulownia lines (Paulownia tomentosa x fortunei and Paulownia elongata x elongata) were investigated. PAM chlorophyll fluorescence measurements revealed that salinity leads to: (i) an increase of the photochemical quenching coefficient (qP) and the linear electron transport rate (ETR) in both lines of Paulownia, while the maximum quantum yield of the primary photochemistry of PSII in the dark adapted state (Fv/Fm) was unaffected; (ii) improved the efficiency of the photochemical energy conversion (FPSII); (iii) an impact on the chlorophyll fluorescence decrease ratio (RFd), which correlates to the net CO2 assimilation rate; (iv) an impact on [Formula: see text] reoxidation. The analysis of the kinetics of P700(+) reduction upon turning off far-red irradiation revealed that salinization lead to a delay of the cyclic electron transport around PSI in both studied lines as the effect on this process is more pronounced in P. tomentosa x fortunei than in (in comparison with) P. elongata x elongata. The present experimental results suggested high salt tolerance of the studied lines Paulownia, but P. tomentosa x fortunei is more tolerant to salinity than P. elongata x elongata. Molecular mechanisms involved in the Paulownia response to the soil salinity are discussed. PMID- 26854408 TI - Characterization of wheat miRNAs and their target genes responsive to cadmium stress. AB - A increasing number of microRNAs have been shown to play important regulatory roles in plant responses to various metal stresses. However, little information about miRNAs especially miRNAs responsive to cadmium (Cd) stress is available in wheat. To investigate the role of miRNAs in responses to Cd stress, wheat seedlings were subjected to 250 MUM Cd solution for 6, 12, 24 and 48 h, and analyses of morphological and physiological changes as well as the expression of five miRNAs and their corresponding targets were carried out. Our results demonstrated that miRNAs and their targets were differentially expressed in leaves and roots of wheat seedlings exposed to Cd stress. Furthermore, miR398 may involve in oxidative stress tolerance by regulating its target CSD to participate in Cd stress. Among ten miRNA-target pairs studied, nine pairs showed complex regulation relationship in leaves and roots of wheat seedlings exposed to Cd stress. These findings suggested that miRNAs are involved in the mediation of Cd stress signaling responses in wheat. The characterization of the miRNAs and the associated targets in responses to Cd exposure provides a framework for understanding the molecular mechanism of heavy metal tolerance in plants. PMID- 26854409 TI - Salt acclimation processes in wheat. AB - Young wheat plants (Triticum aestivum L. cv. Mv Beres) were exposed to 0 or 25 mM NaCl for 11 days (salt acclimation). Thereafter the plants were irrigated with 500 mM NaCl for 5 days (salt stress). Irrigating the plants with a low concentration of NaCl successfully led to a reduction in chlorotic symptoms and in the impairment of the photosynthetic processes when the plants were exposed to subsequent high-dose salt treatment. After exposure to a high concentration of NaCl there was no difference in leaf Na content between the salt-acclimated and non-acclimated plants, indicating that salt acclimation did not significantly modify Na transport to the shoots. While the polyamine level was lower in salt treated plants than in the control, salt acclimation led to increased osmotic potential in the leaves. Similarly, the activities of certain antioxidant enzymes, namely glutathione reductase, catalase and ascorbate peroxidase, were significantly higher in salt-acclimated plants. The results also suggest that while SOS1, SOS2 or NHX2 do not play a decisive role in the salt acclimation processes in young wheat plants; another stress-related gene, WALI6, may contribute to the success of the salt acclimation processes. The present study suggested that the responses of wheat plants to acclimation with low level of salt and to treatment with high doses of salt may be fundamentally different. PMID- 26854410 TI - Molecular cloning and characterization of a novel bi-functional alpha amylase/subtilisin inhibitor from Hevea brasiliensis. AB - A novel cDNA encoding a bi-functional alpha-amylase/subtilisin inhibitor (HbASI) was isolated from rubber (Hevea brasiliensis) leaves cultivar RRIM600. The HbASI had strong homology with the soybean trypsin inhibitor (Kunitz) family of protease inhibitors. Its putative amino acid sequence was similar to that of the alpha-amylase/subtilisin inhibitor from Ricinus communis (72% identity). Genomic sequencing indicated that the HbASI gene contained no introns. The messenger RNA of HbASI was detected in leaf, hypocotyl and root. The recombinant HbASI expressed extracellularly in Pichia pastoris exhibited inhibitory activity against alpha-amylase from Aspergillus oryzae, trypsin and subtilisin A. The HbASI gene was induced in the rubber leaves infected with a rubber tree pathogen, Phytophthora palmivora. It was also enhanced by salicylic acid (SA) treatment and mechanical wounding. In addition, the biological activity of the HbASI protein involving in the plant defence responses was also investigated. The HbASI at a concentration of 0.16 mg mL(-1) could inhibit the mycelium growth of P. palmivora. These data suggested that the HbASI protein might play a crucial role in defence against pathogen of rubber trees. PMID- 26854411 TI - Self-Assembled NiO/Ni(OH)2 Nanoflakes as Active Material for High-Power and High Energy Hybrid Rechargeable Battery. AB - Herein, a proof-of-concept of novel hybrid rechargeable battery based on electrochemical reactions of both nickel-zinc and zinc-air batteries is demonstrated using NiO/Ni(OH)2 nanoflakes self-assembled into mesoporous spheres as the active electrode material. The hybrid battery operates on two sets of fundamentally different battery reactions combined at the cell level, unlike in other hybrid systems where batteries of different reactions are simply connected through an external circuitry. As a result of combining nickel-zinc and zinc-air reactions, the hybrid battery demonstrates both remarkably high power density (volumetric, 14 000 W L(-1); gravimetric, 2700 W kg(-1)) and energy density of 980 W h kg(-1), significantly outperforming the performances of a conventional zinc-air battery. Furthermore, the hybrid battery demonstrates excellent charge rate capability up to 10 times faster than the rate of discharge without any capacity and voltage degradations, which makes it highly suited for large-scale applications such as electric vehicle propulsion and smart-grid energy storage. PMID- 26854412 TI - Bottom-up realization and electrical characterization of a graphene-based device. AB - We propose a bottom-up procedure to fabricate an easy-to-engineer graphene-based device, consisting of a microstrip-like circuit where few-layer graphene nanoplatelets are used to contact two copper electrodes. The graphene nanoplatelets are obtained by the microwave irradiation of intercalated graphite, i.e., an environmentally friendly, fast and low-cost procedure. The contact is created by a bottom-up process, driven by the application of a DC electrical field in the gap between the electrodes, yielding the formation of a graphene carpet. The electrical resistance of the device has been measured as a function of the gap length and device temperature. The possible use of this device as a gas sensor is demonstrated by measuring the sensitivity of its electrical resistance to the presence of gas. The measured results demonstrate a good degree of reproducibility in the fabrication process, and the competitive performance of devices, thus making the proposed technique potentially attractive for industrial applications. PMID- 26854413 TI - Low-Voltage, High-Pitch Computerized Tomography Angiography of the Infrarenal Aorta and Lower Extremity Vessels: Assessment of Radiation Dose, Image Quality With Hybrid Iterative Reconstruction, and Efficacy of Test Injection Using a Monitoring Scan at Knee Level. AB - OBJECTIVES: Our aim was to assess image quality and radiation dose of low-voltage high-pitch computed tomography angiography of the infrarenal aorta and lower extremities and evaluate the efficacy of test injection technique using a monitoring scan at knee level. METHODS: A total of 60 patients with suspected peripheral arterial disease were divided into 2 groups: group 1 (30 patients, 80 kVp, high pitch [3.2], and hybrid iterative reconstruction [sinogram-affirmed iterative reconstruction]) and group 2 (30 patients, 120 kVp, low pitch [1.0], and filtered back projection reconstruction). The test injection technique at knee level was used to determine the scan delay time in group 1. The image quality and radiation exposure were compared. RESULTS: There were significant differences between the 2 groups in mean (SD) arterial attenuation (80 vs 120 kVp: 507.78 [103.01] vs 317.54 [62.03] Hounsfield units, P < 0.001), mean (SD) signal-to-noise ratio (51.04 [20.29] vs 34.66 [9.94], P < 0.001), and contrast-to noise ratio (44.83 [17.93] vs 28.26 [9.60], P < 0.001). No difference in subjective image quality was found between the 2 groups (all P > 0.05). The imaging time was significantly shorter in group 1 (2.70 [0.11] vs 14.65 [0.90s], P < 0.001). The mean (SD) effective dose was significantly lower in the 80 kVp group (0.76 [0.06] vs 4.29 [0.63] mSv, P < 0.001). CONCLUSIONS: The 80-kVp high pitch computed tomography angiography of the lower limbs using sinogram-affirmed iterative reconstruction yields reduction of radiation exposure as well as obtains acceptable image quality if acquisition protocols are used in conjunction with the test injection technique using monitoring scan at knee level to determine the delay time. PMID- 26854414 TI - Prognostic Value of Semiautomatic CT Volumetry in Patients With Stage I Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy. AB - OBJECTIVE: The aim of this study was to examine the prognostic value of semiautomated 3-dimensional image analysis-based parameters from pretreatment computed tomography (CT) in patients with non-small cell lung cancer treated with stereotactic body radiation therapy. METHODS: We evaluated 91 patients. We defined 2 parameters: (1) VOL, extracted tumor volume with a threshold >= -400 HU; and (2) ATN, the mean CT attenuation value. The maximum standardized uptake value (SUVmax) was recorded as F-fluorodeoxyglucose positron emission tomography/CT parameter. The prognostic values were assessed using the Kaplan Meier and a Cox proportional hazards analysis. RESULTS: Overall survival and progression-free survival were significantly worse in patients with larger VOL, higher ATN, and higher SUVmax. VOL was an independent indicator of overall survival, whereas ATN was an indicator of progression-free survival, lymph node recurrence, and distant metastasis. However, SUVmax was not an independent prognostic factor for either outcome. CONCLUSIONS: VOL and ATN from 3-dimensional image analysis of CT scans have prognostic values for non-small cell lung cancer patients treated with stereotactic body radiation therapy. PMID- 26854415 TI - Characteristics of Coronary Artery to Pulmonary Artery Fistula on Coronary Computed Tomography Angiography. AB - OBJECTIVE: The aim of the study was to evaluate the characteristics of coronary artery-to-pulmonary artery fistula (CPAF) found by coronary computed tomography (CT) angiography. METHODS: Among 10,121 cases of coronary CT angiography performed for 7 years, we found 32 cases of CPAF. We retrospectively evaluated the demographics, clinical symptoms, and anatomical characteristics such as the origin, number of origins, course, opening site of the fistula, and the presence of aneurysmal changes (defined as dilatation 1.5 times the diameter of the origin). We also categorized the fistula openings according to size compared with that of the proximal left anterior descending coronary artery. RESULTS: The patients were 14 men and 18 women with a mean (range) age of 56.5 (34-86) years. Nineteen patients had no related symptoms, and the other 13 patients had symptoms such as angina, chest discomfort, palpitations, or shoulder pain. Among these patients, 2 patients were diagnosed with coronary artery disease. The origins of CPAF were single (n = 15, 46.9%) or multiple (n = 17, 53.1%). The CPAFs arose most commonly from the conus branch of the right coronary artery (n = 20, 62.5%) and proximal left anterior descending (n = 17, 53.1%). All CPAFs coursed anteriorly to the main pulmonary artery and drained into the anterolateral aspect. Twenty-five patients (78.1%) exhibited aneurysmal changes. The openings were small in 13 (40.6%), medium in 13 (40.6%), and large in 6 (18.8%) patients. CONCLUSIONS: More than half of patients with CPAF had no related symptoms. Coronary artery-to-pulmonary artery fistula may have a single origin or multiple origins. All of the CPAFs coursed anteriorly to the main pulmonary artery and drained into the anterolateral aspect; the CPAFs identified here frequently exhibited aneurysmal changes. PMID- 26854416 TI - Exponentially Decelerated Contrast Media Injection Rate Combined With a Novel Patient-Specific Contrast Formula Reduces Contrast Volume Administration and Radiation Dose During Computed Tomography Pulmonary Angiography. AB - CLINICAL RELEVANCE: Matching contrast injection timing with vessel dynamics significantly improves vessel opacification and reduces contrast dose in the assessment of pulmonary embolism during computed tomography (CT) pulmonary angiography. PURPOSE: The aim of this study was to investigate opacification of the pulmonary vasculature (PV) during CT pulmonary angiography using a patient specific contrast formula (PSCF) and exponentially decelerated contrast media (EDCM) injection rate. MATERIALS AND METHODS: Institutional review board approved this retrospective study. Computed tomography pulmonary angiography was performed on 200 patients with suspected pulmonary embolism using a 64-channel CT scanner. Patient demographics were equally distributed. Patients were randomly assigned to 2 equal protocol groups: protocol A used a PSCF, and protocol B involved the use of a PSCF combined with EDCM. The mean cross-sectional opacification profile of 8 central and 11 peripheral PVs were measured for each patient, and arteriovenous contrast ratio was calculated. Protocols were compared using Mann-Whitney U nonparametric statistics. Jackknife alternative free-response receiver operating characteristic analyses were used to assess diagnostic efficacy. Interobserver variations were investigated using kappa methods. RESULTS: A number of pulmonary arteries demonstrated increases in opacification (P < 0.02) for protocol B compared with A, whereas opacification in all veins was reduced in protocol B (P < 0.03). Subsequently, increased arteriovenous contrast ratio in protocol B compared with A was observed at all anatomic locations (P < 0.0002). An increase in jackknife alternative free-response receiver operating characteristic figure of merit (P < 0.0002) and interobserver variation was observed with protocol B compared with protocol A (kappa = 0.3-0.73). Mean contrast volume was reduced in protocol B (29 [4] mL) compared with protocol A (33 [9] mL). Mean effective radiation dose in protocol B (1.2 [0.4] mSv) was reduced by 14% compared with protocol A (1.4 [0.6] mSv). CONCLUSIONS: Significant improvements in visualization of the PV can be achieved with a low contrast volume using an EDCM and PSCF. The reduced risk of cancer induction is highlighted. PMID- 26854417 TI - Impact of Implementing Cardiac CT in Evaluating Patients Suspected of Cardioembolic Stroke. AB - BACKGROUND AND OBJECTIVES: In practice, clinical and logistic hurdles may hamper performing transesophageal echocardiography in stroke patients. Cardiac computed tomography (CT) is a recently introduced noninvasive modality able to detect various embolic causes. Thus, we retrospectively assessed possible added values of applying cardiac CT in the real-world work-up of suspected cardioembolic stroke cases. METHODS: Forty-seven patients were neurology service referrals for suspected cardioembolic stroke. The CT images and clinical reports of our cardiac CT radiologists were retrospectively evaluated. Cardiac CT was assessed in terms of detecting major embolic potential findings, potentially significant stroke unrelated findings, and coronary arterial disease (CAD). Computed tomography results were correlated with echocardiographic reports. RESULTS: Cardiac CT showed findings of major embolic potential in 10 patients (21%, 5 thrombi cases, 2 vasculitis cases, 1 case of metastasis invading the left superior pulmonary artery, 1 myocardial infarction case, and 1 pulmonary arteriovenous malformations case), none of which were documented in echocardiography reports. Two cases (4%) with findings of major embolic potential where identified on echocardiography but not on CT (1 left atrial appendage thrombus and 1 mitral valve vegetation). Computed tomography of 13 patients (28%) showed 16 potentially significant stroke unrelated findings. Twenty-one patients (47%) had unexpected CAD on CT, 11 (52%) of which were obstructive. CONCLUSIONS: Implementing cardiac CT in assessing patients suspected of cardioembolic stroke added value to echocardiographic evaluation, by detecting major embolic potential findings. In addition, cardiac CT revealed additional potentially significant stroke-unrelated findings and CAD. PMID- 26854418 TI - Electronic Health Record Adoption and Rates of In-hospital Adverse Events. AB - OBJECTIVE: Nationwide initiatives have focused on improving patient safety through greater use of health information technology. We examined the association of hospitals' electronic health record (EHR) adoption and occurrence rates of adverse events among exposed patients. METHODS: We conducted a retrospective analysis of patient discharges using data from the 2012 and 2013 Medicare Patient Safety Monitoring System. The sample included patients age 18 and older that were hospitalized for one of 3 conditions: acute cardiovascular disease, pneumonia, or conditions requiring surgery. The main outcome measures were in-hospital adverse events, including hospital-acquired infections, adverse drug events (based on selected medications), general events, and postprocedural events. Adverse event rates and patient exposure to a fully electronic EHR were determined through chart abstraction. RESULTS: Among the 45,235 patients who were at risk for 347,281 adverse events in the study sample, the occurrence rate of adverse events was 2.3%, and 13.0% of patients were exposed to a fully electronic EHR. In multivariate modeling adjusted for patient and hospital characteristics, patient exposure to a fully electronic EHR was associated with 17% to 30% lower odds of any adverse event for cardiovascular (odds ratio [OR], 0.80; 95% confidence interval [CI], 0.72-0.90), pneumonia (OR, 0.70; CI, 0.62-0.80), and surgery (OR, 0.83; CI, 0.72-0.96) patients. The associations of EHR adoption and adverse events varied by event type and by medical condition. CONCLUSIONS: Cardiovascular, pneumonia, and surgery patients exposed to a fully electronic EHR were less likely to experience in-hospital adverse events. PMID- 26854419 TI - Automatically quantifying the scientific quality and sensationalism of news records mentioning pandemics: validating a maximum entropy machine-learning model. AB - OBJECTIVE: To develop and validate a method for automatically quantifying the scientific quality and sensationalism of individual news records. STUDY DESIGN: After retrieving 163,433 news records mentioning the Severe Acute Respiratory Syndrome (SARS) and H1N1 pandemics, a maximum entropy model for inductive machine learning was used to identify relationships among 500 randomly sampled news records that correlated with systematic human assessments of their scientific quality and sensationalism. These relationships were then computationally applied to automatically classify 10,000 additional randomly sampled news records. The model was validated by randomly sampling 200 records and comparing human assessments of them to the computer assessments. RESULTS: The computer model correctly assessed the relevance of 86% of news records, the quality of 65% of records, and the sensationalism of 73% of records, as compared to human assessments. Overall, the scientific quality of SARS and H1N1 news media coverage had potentially important shortcomings, but coverage was not too sensationalizing. Coverage slightly improved between the two pandemics. CONCLUSION: Automated methods can evaluate news records faster, cheaper, and possibly better than humans. The specific procedure implemented in this study can at the very least identify subsets of news records that are far more likely to have particular scientific and discursive qualities. PMID- 26854421 TI - Corrigendum: Profiling RNA editing in human tissues: towards the inosinome Atlas. PMID- 26854420 TI - Brief alcohol intervention trials conducted by higher prestige authors and published in higher impact factor journals are cited more frequently. AB - OBJECTIVE: To examine the relationships between study quality, author prestige, journal impact factors, and citation rates of trials and to examine whether journal impact factors mediated the relationships between study quality and author prestige on citation rates. STUDY DESIGN AND SETTING: We used bibliometric data from 128 controlled trials included in a recent meta-analysis on brief alcohol interventions for adolescents and young adults. We obtained the number of citations from ISI Web of Knowledge and Google Scholar; journal impact factors were obtained from ISI Web of Knowledge. Linear regression models were used to examine the direct and indirect effects of interest. RESULTS: The results indicated that studies were published in journals with higher impact factors when first authors had higher h-indices and studies were funded, but this was largely because those studies were of higher quality. Studies were cited more frequently when first authors had higher h-indices and studies were funded, even after adjusting for study quality proxies. The observed associations between study quality and author prestige on citation rates were also partly mediated through journal impact factors. CONCLUSION: We conclude that studies conducted by more established authors and reported in more prestigious journal outlets are more likely to be cited by other scholars, even after controlling for various proxies of study quality. PMID- 26854422 TI - The effect of home bleaching agents on the surface roughness of five different composite resins: A SEM evaluation. AB - The aim of this study was to investigate the effect of hydrogen peroxide (HP) and carbamide peroxide (CP) on the surface roughness of five different composite resins using profilometer and scanning electron microscope (SEM). Thirty-six specimens (1 mm thick, 10 mm in diameter) of five composite resins were fabricated. Each composite group was equally divided into three subgroups as control, CP and HP. In control group, specimens were stored in daily refreshed distilled water during the 14-day testing period. In other groups, 10% HP (Opalescence Treswhite) and 10% CP (Opalescence PF) were applied and surface roughness values (Ra) of each specimen were measured with a profilometer at the end of 14 days. Additionally, SEM analysis was performed to evaluate the surface deformations of composite resins. Data were analyzed with Kruskal-Wallis and Mann Whitney U tests. Ra values of composite groups exposed to bleaching agents were statistically higher than control group (p < 0.05). There was no significant difference between Ra values after HP and CP application within each composite group while SEM micrographs showed higher surface alterations at HP group compared to CP. Among the composite resins tested, Ceram-X Mono revealed the lowest Ra values after CP and HP applications as seen at SEM images. Home bleaching agents increased the surface roughness of all composites. Except CP applied Ceram-X mono specimens, Ra values of all composite resins evaluated in this study exceeded the critical limit of 0.2 MUm. Ceram-X mono was the least affected composite material after bleaching application. SCANNING 38:277-283, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26854423 TI - Developing timely insights into comparative effectiveness research with a text mining pipeline. AB - Comparative effectiveness research (CER) provides evidence for the relative effectiveness and risks of different treatment options and informs decisions made by healthcare providers, payers, and pharmaceutical companies. CER data come from retrospective analyses as well as prospective clinical trials. Here, we describe the development of a text-mining pipeline based on natural language processing (NLP) that extracts key information from three different trial data sources: NIH ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and Citeline Trialtrove. The pipeline leverages tailored terminologies to produce an integrated and structured output, capturing any trials in which pharmaceutical products of interest are compared with another therapy. The timely information alerts generated by this system provide the earliest and most complete picture of emerging clinical research. PMID- 26854425 TI - Exogenous nucleosome-binding molecules: a potential new class of therapeutic drugs. AB - Constant changes in the structure of chromatin regulate gene expression. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Conceptually, the nucleosome was first identified as a therapeutic target 14 years ago, when small molecules started to be elegantly designed for nucleosomal DNA binding. Concomitantly, emergent drugs that target enzymes that affect chromatin structure have been developed to a treat myriad of diseases, such as cancer. Here, we discuss the development of more complex molecules, such as peptides and peptidomimetics, to directly target the nucleosome surface to modulate chromatin structure. This new strategy presents great challenges that need to be overcome to develop the exogenous nucleosome-binding molecules (eNBMs) as therapeutic agents. PMID- 26854426 TI - Quality-by-design based development of a self-microemulsifying drug delivery system to reduce the effect of food on Nelfinavir mesylate. AB - Poor aqueous solubility and moderate permeability of Nelfinavir mesylate (NFM) leads to high variability in absorption after oral administration. To improve the solubility and bioavailability of NFM, the self microemulsifying drug delivery system (SMEDDS) was developed. For this purpose, Quality by design (QbD) approach employing D-optimal mixture design was used to prepare SMEDDS of NFM. Further, the software generated numerically optimized SMEDDS were developed by utilizing desirability function. Maisine 35-1, Tween 80, and Transcutol HP were identified as oil, surfactant, and co-surfactant that had best solubility for NFM. Ternary phase diagrams were plotted to identify the self-emulsification region. Dissolution of putative NFM in simulated fasted or fed small intestinal conditions, respectively, predicted that there is a positive food effect. However, NFM loaded SMEDDS showed absence of food effect with no significant difference in dissolution performance either in Fasted or fed state simulated intestinal fluid (FaSSIF or FeSSIF) biorelevent dissolution media. The prepared SMEDDS were thermodynamically stable with droplet size (121 nm), poly dispersity index (PDI) (0.198) and emulsification time (<1 min). Transmission electron microscopy (TEM) analysis confirmed the spherical shape of the reconstituted SMEDDS droplets. The ex vivo performance revealed 4.57 fold enhancement in the apparent permeability of NFM as compared to NFM suspension. The animal pharmacokinetic analysis in New Zealand strain rabbits indicated food effect on pure NFM suspension. However, absence of food effect and 3.5-3.6 fold enhancement in the oral bioavailability was observed when NFM was formulated into SMEDDS. Thus, it could be envisaged that development of SMEDDS formulation of NFM could be one of the best alternative to enhance oral bioavailability of NFM. PMID- 26854424 TI - Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity. AB - Major depression is a chronic and debilitating illness that effects approximately 1 in 5 people, but currently available treatments are limited by low rates of efficacy, therapeutic time lag, and undesirable side effects. Recent efforts have been directed towards investigating rapid-acting agents that reverse the behavioral and neuronal deficits of chronic stress and depression, notably the glutamate NMDA receptor antagonist ketamine. The cellular mechanisms underlying the rapid antidepressant actions of ketamine and related agents are discussed, as well as novel, selective glutamatergic receptor targets that are safer and have fewer side effects. PMID- 26854427 TI - Investigating the influence of drug aggregation on the percutaneous penetration rate of tetracaine when applying low doses of the agent topically to the skin. AB - Understanding the molecular aggregation of therapeutic agents is particularly important when applying low doses of a drug to the surface of the skin. The aim of this study was to understand how the concentration of a drug influenced its molecular aggregation and its subsequent percutaneous penetration after topical application. A model drug tetracaine was shown to form a series of different aggregates across the MUM (fluorescence spectroscopy) to mM (light scattering analysis) concentration range. The aggregate formation process was sensitive to the pH of the vehicle in which the drug was dissolved (pH 4, critical aggregation concentration (CAC) - 11 MUM; pH 8, CAC - 7 MUM) and it appeared to have an impact upon the drug's percutaneous penetration. At pH 4, increasing the concentration of the drug in the donor solution decreased the skin permeability coefficient (Kp) of tetracaine (13.7 +/- 4.3 * 10(-3)cm/h to 0.06 +/- 0.02 * 10( 3)cm/h), whilst at pH 8, it increased the Kp (29.9 +/- 9.9 * 10(-3)cm/h to 75.1 +/- 41.7 * 10(-3)cm/h). These data trends were reproduced in a silicone membrane and this supported the notion that the more polar aggregates formed at pH 4 acted to decrease the proportion of species available to pass through the skin, whilst the more hydrophobic aggregates formed in pH 8 increased the membrane diffusing species. PMID- 26854428 TI - Bioactive glass combined with bisphosphonates provides protection against biofilms formed by the periodontal pathogen Aggregatibacter actinomycetemcomitans. AB - Biofilms play a pivotal role in the progression of periodontitis and they can be treated with antiseptics (i.e. chlorhexidine) or antibiotics, but these therapeutic alternatives are unable of ameliorating periodontal alveolar bone loss, which has been, on the other hand, successfully treated with bone preserving agents. The improved bone formation achieved in animal models by the combination of two such agents: bioactive glass (BAG) and bisphosphonates has attracted the interest for further exploring dental applications. However, the antimicrobial effects that may result from combining them have not been yet investigated. Here, our aim was to explore the anti-biofilm effects that could result from combining BAG with bisphosphonates, particularly in a dental biofilm model. The experiments were performed with an oral cavity single-specie (Aggregatibacter actinomycetemcomitans) biofilm assay, which was optimized in this contribution. Risedronate displayed an intrinsic anti-biofilm effect, and all bisphosphonates, except clodronate, reduced biofilm formation when combined with BAG. In particular, the anti-biofilm activity of risedronate was significantly increased by the combination with BAG. Since it has been proposed that some of the antimicrobial effects of BAG are caused by local pH changes, studies of pH variations were performed to gain a mechanistic understanding. However, the observed anti-biofilm effects could not be explained with lowered pHs. Overall, these results do provide further support for the promising use of bisphosphonate-BAG combinations in dental applications. These findings are particularly relevant for patients undergoing cancer chemotherapy, or osteoporotic patients, which are known to be more vulnerable to periodontitis. In such cases, bisphosphonate treatment could play a double positive effect: local treatment of periodontitis (in combination with BAG) and systemic treatment of osteoporosis, prevention of hypercalcemia and metastases. PMID- 26854429 TI - Combinations of colistin solutions and nebulisers for lung infection management in cystic fibrosis patients. AB - In this work different nebulisers were investigated in order to assess their efficiency in combination with colistimethate sodium (CMS) inhalation products. Four nebulisers, namely I-neb((r)), Aeroneb((r)) Go, eFlow((r))rapid and PARI LC((r)) Sprint were studied in terms of delivered dose (DD), drug delivery rate (DDR) and respirable dose (RD) of CMS. The goal was to provide scientific data to physicians for prescribing the most appropriate nebuliser for the CMS specific user. All the apparatuses nebulised ColiFin 1MIU/3 ml solution (80 mg of CMS) with delivered doses between 31% and 41% of the loaded amount. Aeroneb Go showed the longest nebulisation time (more than 20 min). When ColiFin 2 MIU/4 ml was nebulised with eFlow rapid or PARI LC Sprint, the CMS respirable dose was 45.3mg and 39.2mg, in times of 5.6 and 10.8 min, respectively. I-neb, having a medication cup capacity limited to 0.4 ml, loaded with Promixin 0.4 MIU/0.4 ml (32 mg of CMS), provided in a time of 9 min a RD of 21.5mg, a value slightly higher than those obtained by nebulising ColiFin 1 MIU/3 ml with the other nebulisers (range 15.9-17.6 mg). The results illustrate that the clinical outcome depends on the comparative analysis of nebulisation efficiency (respirable dose) and convenience (time), not disregarding the ratios between the amount loaded, delivered and deposited at lung level. PMID- 26854431 TI - Synthesis, structure elucidation, DNA-PK and PI3K and anti-cancer activity of 8- and 6-aryl-substituted-1-3-benzoxazines. AB - The synthesis of 6-aryl, 8- aryl, and 8-aryl-6-chloro-2-morpholino-1,3 benzoxazines with potent activity against PI3K and DNA-PK is described. Synthesis of thirty one analogues was facilitated by an improved synthesis of 3-bromo-2 hydroxybenzoic acid 13 by de-sulphonation of 3-bromo-2-hydroxy-5-sulfobenzoic acid 12 en route to 2-methylthio-substituted-benzoxazine intermediates 17-19. From this series, compound 20k (LTURM34) (dibenzo[b,d]thiophen-4-yl) (IC50 = 0.034 MUM) was identified as a specific DNA-PK inhibitor, 170 fold more selective for DNA-PK activity compared to PI3K activity. Other compounds of the series show markedly altered selectivity for various PI3K isoforms including compound 20i (8 (naphthalen-1-yl) a potent and quite selective PI3Kdelta inhibitor (IC50 = 0.64 MUM). Finally, nine compounds were evaluated and showed antiproliferative activity against an NCI panel of cancer cell lines. Compound 20i (8-(naphthalen-1 yl) showed strong anti-proliferative activity against A498 renal cancer cells that warrants further investigation. PMID- 26854432 TI - Emerging therapies targeting castration-resistant prostate cancer. AB - PURPOSE: Building on decades of research, the past few years have yielded a near expo-nential increase in treatment modalities for patients with metastatic prostate cancer. Individually, these improvements in overall survival may appear modest, however, nearly all of them have a distinct mechanism of action and the possibility of synergistic effects have yet to be established. The promise of a durable impact on the mortality from metastatic prostate cancer will likely stem from further elucidation of molecular pathways involved in prostate cancer, as well as defining the optimal sequence of treatment for patients with metastatic prostate cancer. PMID- 26854430 TI - Novel cis-selective and non-epimerisable C3 hydroxy azapodophyllotoxins targeting microtubules in cancer cells. AB - Podophyllotoxin (PT) and its clinically used analogues are known to be powerful antitumour agents. These compounds contain a trans fused strained gamma-lactone system, a feature that correlates to the process of epimerisation, whereby the trans gamma-lactone system of ring D opens and converts to the more thermodynamically stable cis epimer. Since these cis epimers are known to be either less active or lacking antitumour activity, epimerisation is an undesirable feature from a chemotherapeutic point of view. To circumvent this problem, considerable efforts have been reported, amongst which is the synthesis of azapodophyllotoxins where the stereocentres at C2 and C3 are removed in order to preclude epimerisation. Herein we report the identification of a novel C3 hydroxy, cis-selective gamma-lactone configuration of ring C in the azapodophyllotoxin scaffold, through an efficient stereoselective multicomponent reaction (MCR) involving fluorinated and non-fluorinated aldehydes. This configuration releases the highly strained trans gamma-lactone system in podophyllotoxin analogues into the more thermodynamically stable cis gamma lactone motif and yet retains significantly potent activity. These compounds were evaluated against the human cancer lines MCF-7 and 22Rv1 in vitro. Fourteen out of the seventeen tested compounds exhibited sub-micromolar activity with IC50 values in the range of 0.11-0.91 MUM, which is comparable and in some cases better than the activity profile of etoposide in this assay. Interestingly, we obtained strong evidence from spectroscopic and X-ray data analyses that the previously reported structure of similar analogues is not accurate. Molecular modelling performed using the podophyllotoxin binding site on beta tubulin revealed a novel binding mode of these analogues. Furthermore, sub-cellular study of our compounds using immunolabelling and confocal microscopy analyses showed strong microtubule disruptive activity, particularly in dividing cells. PMID- 26854433 TI - Bladder cancer risk from the perspective of genetic polymorphisms in the carcinogen metabolizing enzymes. AB - Urinary bladder cancer is a socially significant healthcare problem. A diverse array of aromatic and heterocyclic amines, derived from the chemical and transport industry, diet, and cigarette smoke are considered carcinogens for the bladder. To exert their carcinogenic effect and to initiate the carcinogenic response, the arylamines require a metabolic activation by the host enzymes to chemically reactive compounds. The aim of this article was to review the latest and basic research developments on the role of the polymorphisms in the carcinogen metabolizing enzymes N-acetyltransferase (NAT), Glutathione S transferases (GST), and Soluble sulfotransferases (SULT), with emphasis on the susceptibility to urinary bladder cancer. A PubMed search was conducted to identify original and review articles containing information about these polymophic variants in different populations and according to their prevalence in bladder cancer patients. We noticed that some genotypes were found to be predisposing and some protective for bladder cancer development. The NAT2 slow genotype, together with GSTM1 null genotype facilitated the development of bladder cancer in almost all ethnic groups. The 213His allele of the SULT1A1 gene which is associated with lower enzyme activity and decreased mutagen activation was reported to protect from bladder cancer in almost all studies. PMID- 26854434 TI - Young age and pathological features predict breast cancer outcome - report from a dual Institution experience in Serbia. AB - PURPOSE: The aim of this study was to investigate the influence of clinicopathological and biological characteristics on prognosis, disease free survival (DFS) and overall survival (OS), of very young patients (<=35 years of age) with breast cancer. METHODS: We retrospectively collected information of 150 women diagnosed with breast cancer, aged <=35 years, who were operated and treated at two University Hospitals in Serbia between January 2009 and February 2011. RESULTS: After a median follow up of 44 months patients <=30 had shorter DFS and OS compared to patients aged 31-35 years (p=0.004 and p=0.037, respectively). The differences in DFS and OS were significant with decreased survival associated with higher tumor grade (p=0.005 and p=0.0001, respectively). Tumor size and number of positive nodes were predictors of outcome with decreased survival associated with higher tumor size (p=0.0019 for DFS and p<0.0001 for OS) and increasing number of nodes (p<0.0001 for both). HER 2 receptor did not seem to have a prognostic influence while patients with hormonal receptors (HRs) positive tumors had a better DFS (p=0.034) and OS (p=0.046) than those with HRs negative tumors. In univariate survival analysis, a significant difference in DFS (p=0.0003) and OS (p=0.0003) was found between patients with vs without lymphovascular invasion (LVI). CONCLUSION: Diagnosis of breast cancer at very young age (<30) was associated with increased risk of death and shorter DFS than women aged 31-35. Negative impact on survival was seen in patients with presence of LVI, negative HRs and higher grade and stage at the time of presentation. PMID- 26854435 TI - Aurora A overexpression in breast cancer patients induces taxane resistance and results in worse prognosis. AB - PURPOSE: The aim of this study was to determine the expression level of Aurora A in human breast cancer tissues and to test whether there is a relationship between its expression levels and clinicopathological parameters including response to taxanes, tumor grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, and overall survival (OS). METHODS: We retrospectively analyzed paraffin-embedded tissue sections from 49 metastatic breast cancer patients whose clinical outcomes had been tracked after taxane treatment. The expression status of Aurora A was defined by immunohistochemistry (IHC) using the anti-Aurora A antibody. RESULTS: Aurora A was overexpressed in 73% of the examined specimens. There was significant correlation between high Aurora A expression and decreased taxane sensitivity (p=0.02). There was no association between the clinicopathological parameters including histologic grade, ER positivity and triple negative molecular subtype and the level of Aurora A expression. However, HER2 positive tumors showed significantly higher Aurora A expression compared with HER2 negative tumors (p=0.02). Kaplan-Meier survival analysis failed to show a significant correlation between expression levels of Aurora A and OS although patients with low Aurora A levels had a marginally longer survival compared to patients with high levels. CONCLUSION: Our data suggest that Aurora A may be a promising predictive and prognostic marker in patients with breast cancer. PMID- 26854436 TI - Pharmacotherapeutic recommendations for application of target oncological drug therapies for treatment of breast cancer in Bulgaria - therapeutic efficacy and cost effectiveness. AB - PURPOSE: The purpose of this study was to determine the direct costs of targeted cancer therapies for the treatment of breast cancer, calculating the effectiveness of the additional costs (ICER) and the cost of life years gained (LYG), using data from randomized clinical trials cited in the summary of product characteristics (SPC) of medicinal products approved for use under the centralized procedure. METHODS: Data from the SPC and clinical trials was analyzed. ICER and LYG of the medicinal therapies were compared using data from Phase III clinical trials cited in the Summary of product characteristics. The perspective of the payer was adopted. RESULTS: The SPCs of five drugs were analyzed. Targeted therapies were compared to placebo or to best supportive care (BSC) in some of them, while in others monoclonal antibodies (mAbs) and tyrosine kinase inhibitors were compared to existing drug therapies. Cost-effectiveness of each therapy was calculated. The value of ICER was between 56 470 Bulgarian Levs/LYG and 879 480 Bulgarian Levs/LYG. CONCLUSION: The current pharmacotherapeutic recommendations for targeted therapies for the treatment of breast cancer are based on evidence of therapeutic efficacy and cost effectiveness. Their application in therapeutic practice in Bulgaria is necessary to ensure patient access to effective therapies within the limited public funds. PMID- 26854437 TI - Erythropoietin receptor and tissue factor are coexpressed in human breast cancer cells. AB - PURPOSE: Erythropoiesis-stimulating agents (ESAs) are recommended for treating chemotherapy-induced anemia in breast cancer patients. Reduced survival rates in ESAs-treated patients have been reported, possibly due to thromboembolic complications, however the exact mechanism remains obscure. The principal activator of blood coagulation in cancer is tissue factor (TF). There are data that erythropoietin receptor (EPO-R) is expressed in tumor cells. The purpose of this study was to evaluate the expression of EPO-R and TF in loco in breast cancer. METHODS: The expression of EPO-R and TF was investigated in 24 invasive breast carcinoma specimens. Immunohistochemical (IHC) methodologies according to ABC technique and double-staining IHC procedure were employed utilizing antibodies against EPO-R and TF. RESULTS: Expression of EPO-R and TF was demonstrated in the tumor cells in all breast cancer specimens. No staining for EPO-R and TF was visualized in normal breast tissue. Double staining studies revealed co-expression of both EPO-R and TF in breast cancer cells and endothelial cells. CONCLUSIONS: EPO-R and TF expression and their coexpression in breast cancer cells suggest a possibility that EPO-R might be responsible for some adverse effects and reduced survival observed in ESAs-treated breast cancer patients with anemia, possibly due to the interaction with TF. Further experimental studies are warranted to determine the role of both EPO-R and TF in the treatment with ESAs of breast cancer patients with chemotherapy-induced anemia. PMID- 26854438 TI - Predicting the role of the pretreatment neutrophil to lymphocyte ratio in the survival of early triple-negative breast cancer patients. AB - PURPOSE: Increasing evidence supports an association between systemic inflammation and cancer development and progression. The neutrophil to lymphocyte ratio (NLR) is used as a basic parameter of systemic inflammation in some tumors. The aim of this study was to examine the association between the pretreatment NLR, disease-free survival (DFS), and overall survival (OS) in patients with early triple-negative breast cancer (TNBC). METHODS: We retrospectively studied patients diagnosed with stage I-III TNBC who had completed all phases of primary treatment from 2002 to 2013. The association between the pretreatment NLR and survival was analyzed. The difference among variables was calculated by chi square test. OS and DFS were assessed using the Kaplan-Meier method. Multivariate Cox proportional hazards models were used to analyze the prognostic impact of clinical parameters. RESULTS: Eighty-five patients were eligible for study inclusion. There were no statistically significant differences among the pretreatment NLR and clinicopathological variables. Patients with an NLR of > 2 had significantly lower DFS (p=0.002) and OS (p=0.03) than patients with an NLR of <= 2. Multivariate Cox proportional hazards models showed that a higher pretreatment NLR was independently correlated with poor DFS and OS, with a hazard ratio 5.46 (95% confidence interval [CI] 1.61-18.85, p=0.006) and 2.86 (95% CI 1.04-7.86, p=0.04), respectively. CONCLUSION: Patients with early TNBC and with elevated pretreatment NLR showed poorer DFS and OS than patients without elevated NLR. However, this finding needs to be confirmed in a large prospective study. PMID- 26854439 TI - Comparison of the long-term outcomes of patients who underwent laparoscopic versus open surgery for rectal cancer. AB - PURPOSE: Survival data of patients who underwent laparoscopic surgery compared with those who underwent open surgery for rectal cancer are limited. We compared long-term outcomes of laparoscopic surgery with those of open surgery in patients with rectal cancer. METHODS: Between April 2007 and December 2013, a series of 879 patients with rectal cancer underwent surgery with curative intent (287 patients via laparoscopic surgery and 592 patients via open surgery). Age, gender, body mass index (BMI), American Society of Anesthesiologists (ASA) score, clinical stage and type of resection were matched by propensity scoring, and 382 patients (191 patients by laparoscopic surgery and 191 patients by open surgery) were selected for analysis. Intraoperative factors, postoperative data, long-term survival were evaluated. RESULTS: There was no significant difference in preoperative data between the two patient groups. Blood loss was significantly lower in the laparoscopy group than in the open group, while operation time was significantly longer in the laparoscopy group than the open group. There were no significant differences in overall survival or recurrence-free survival. The patterns of recurrence were not different between the two groups. CONCLUSION: Laparoscopic surgery for patients with rectal cancer produces the same long-term results compared with open surgery in terms of survival and recurrence. PMID- 26854440 TI - Laparoscopic rectal resection versus conventional open approach for rectal cancer - a 4-year experience of a single center. AB - PURPOSE: This study was carried out to compare the therapeutic outcomes and complications of the laparoscopic and the conventional open surgery technique used for treating rectal cancer. Another goal was to find the fastest and most accurate method of treatment for rectal cancer, along with establishing the advantages and disadvantages of the two surgical techniques, depending on cancer location and its stage. METHODS: A total of 172 patients diagnosed with rectal cancer and hospitalized in the Department of Surgery III between January 1st 2008 and December 31st 2011 were studied. The laparoscopic approach was performed on 29 (16.8%) patients, and the remaining 143 (83.2%) underwent the conventional Miles/Lloyd-Davies abdominoperineal resection. A longitudinal study was conducted on patients with rectal resection, the used data being obtained from the database of the Department of Surgery III, hospital records, protocols and clinical charts of rectal cancer cases. RESULTS: There were no statistically significant differences regarding symptoms, gender, age, body mass index (BMI), tumor site, TNM stage, intraoperative accidents, operative time, and postoperative mortality between the two groups. The laparoscopic group presented advantages regarding antibiotic and analgesic therapy, early mobilization, hospital stay, intraoperative blood loss, resuming oral nutrition, bowel transit resumption, postoperative complications and wound complications. CONCLUSION: Laparoscopic abdominoperineal resection for rectal cancer is feasible, safe and effective. It can be safely performed by an experienced team, reducing the rate of postoperative complications, the need for blood transfusions, the adminstration of antibiotics and painkillers, allowing faster bowel transit resumption, shortening hospital stay and providing superior aesthetic results. PMID- 26854441 TI - An adoptive T cell immunotherapy targeting cancer stem cells in a colon cancer model. AB - PURPOSE: Colon cancer is one of the most common malignancies worldwide. Cancer stem-like cells (CSCs) are a distinct subgroup of cancer cells that play a vital role in the development of cancer and also a role in the development of resistance against therapeutic agents. In this study we investigated the role of CSCs in colon cancer and evaluated the tumor-associated antigen CEP55 for targeting immunotherapeutically CSCs. METHODS: Side population (SP) cells from colon cancer cell line SW480, were isolated using DNA-binding dye Hoechst 33342. The cytotoxic activity of cytotoxic T lymphocytes (CTL) clone 41 for side population (SP) cells and main population (MP) cells was evaluated using 51Cr release assay. The SP cells, MP cells and presorted cells from the colon cancer cell line were evaluated in NOD/SCID mice. RESULTS: The isolated SP cells showed resistance to the chemotherapeutic agents irinotecan and oxaliplatin, which suggests that targeting the CSCs can be a better strategy for the treatment of chemotherapy-resistant colon cancer. HLA class I and HLA-A24 in SP cells and MP cells were expressed at the same level. We used CTL clone 41 to corroborate the sensitivity of SP cells to cytotoxic T lymphocyte response. The cytotoxic responses of SP cells were to the same extent as they were in MP cells and pre sorted cells. Adoptive transfer of CTL clone 41 in immunodeficient mice inhibited SW480-induced tumors, suggesting that this approach can be used for colon cancer immunotherapy. CONCLUSION: Our novel findings suggest that colon cancer CSCs are sensitive to CTLs, and CEP55, a tumor-associated antigen, can be successfully used as active immunotherapy for targeting CSCs in colon cancer. PMID- 26854442 TI - Heat shock protein 70 is a useful marker for predicting colorectal cancer. AB - PURPOSE: In colorectal cancer (CRC), as in most of other malignancies, heat shock proteins (HSPs) are overexpressed and are associated with apoptosis, cancer cell proliferation, differentiation, invasion, and metastasis. HSP70 is one of the HSPs and has a promising future in cancer studies for both diagnostic and therapeutic applications. In this study, we tried to evaluate the serum levels of HSP70 in CRC patients, and to evaluate its predictive value of detecting CRC. METHODS: This prospective study was consisted of 33 patients diagnosed with CRC and 31 healthy subjects who were matched for age. Enzyme-linked immunosorbent assays (ELISA) were used to evaluate the serum levels of HSP70 in patients with CRC and in the healthy control group. A cut-off value for HSP70 was also determined using receiver operating characteristic (ROC) curve analysis. RESULTS: Patients with CRC had significantly higher HSP70 concentrations compared with the control group (4.52 +/- 1.83 vs 1.22 +/- 0.48 ng/ml, p=0.001), the cut-off value was >=2.25 ng/ml (95% CI 0.993-1.003, p<0.001). The sensitivity and specificity of elevated serum HSP70 in the CRC group were 96.77 and 96.96%, respectively. Also, HSP70 levels were significantly higher with rectal disease localization (p=0.01). CONCLUSION: This study shows that the serum level of HSP70 is elevated in patients with CRC. HSP70 may be utilized as an adjunct to other diagnostic or screening tests. PMID- 26854443 TI - Therapeutic silencing of HPV 16 E7 by systemic administration of siRNA-neutral DOPC nanoliposome in a murine cervical cancer model with obesity. AB - PURPOSE: To evaluate the effectiveness of a neutral DOPC nanoliposome system for the delivery of siRNA to tumor cells in an obese murine cervical cancer model. METHODS: In vitro silencing of E6-E7 mRNA and E7 protein using siRNAE6 or siRNAE7 was analyzed in TC-1 cells by RT-PCR and Western blot. Silencing and antitumor capacities of siRNAE7-DOPC-nanoparticles (NP) were tested in vivo in both normal and obese mice using qPCR. These NPs were administered twice a week for 15 days and tumor volume and weight were recorded. RESULTS: Levels of in vitro E6-E7 silencing were 90% for mRNA and 60% for protein when siRNAE7 was used. On the other hand when siRNAE6 was used, the levels of silencing were 50% for E6-E7 mRNA and only 20% for protein. In vivo E7 mRNA silencing by siRNAE7-DOPC-NP was similar (60%) in both non-obese and obese mouse models. The therapeutic study showed a 65% decrease in tumor volume and a 57% reduction in tumor weight as compared to the control groups. CONCLUSION: There was no negative impact of obesity on the antitumor activity of siRNA-DOPC-NP in obese mice. PMID- 26854444 TI - Inhibitory effect of Aphidicolin - a tetracyclic diterpene - on the proliferation and apoptotic induction in human cervical cancer (HeLa) cells. AB - PURPOSE: The objective of the present work was to investigate the antitumor and apoptotic effect of aphidicolin against human cervical cancer (HeLa) cells. METHODS: Flow cytometry was performed to detect alterations in the mitochondrial membrane potential loss (DeltaPsim) after aphidicolin treatment. Cell viability was assessed by the MTT assay while the apoptotic effects of the compound were examined by fluorescence microscopy and flow cytometry. RESULTS: Aphidicolin induced dose-dependent as well as time-dependent cytotoxic effects in HeLa cells. Chromatin condensation and formation of apoptotic bodies were observed by Hoechst 33258 staining after drug treatment. Aphidicolin induced both early and late apoptosis in HeLa cells which were correlated with strong concentration of the compound. DeltaPsim was also observed following aphidicolin treatment at varying doses. CONCLUSION: Aphidicolin is a potent antitumor and apoptotic agent against human cervical carcinoma and its effects are mediated via chromatin condensation and mitochondrial membrane potential loss. PMID- 26854445 TI - Antiproliferative and apoptotic effects of the ethanolic herbal extract of Achillea falcata in human cervical cancer cells are mediated via cell cycle arrest and mitochondrial membrane potential loss. AB - PURPOSE: Cervical carcinoma is the second most common malignancy in females and most of the cases are found in developing countries. The objectives of the present study were (a): to demonstrate the antiproliferative and apoptotic effects of Achillea falcata (A.falcata) extract in human cervical cancer cells (HeLa), and (b): to study the effect of the extract on cellular morphology, cell cycle phase distribution and mitochondrial membrane potential. METHODS: MTT assay was used to evaluate the anticancer effect of the extract on HeLa cells. Phase contrast, fluorescence microscopy and transmission electron microscopy (TEM) were used to investigate the morphological changes in these cancer cells after extract treatment. Flow cytometry was used to evaluate the effects of the extract on cell cycle and mitochondrial membrane potential. RESULTS: The results revealed that A. falcata extract led to a significant antiproliferative effect in HeLa cancer cells. The extract induced cellular shrinkage, chromatin condensation and appearance of apoptotic bodies which are the hallmarks of cellular apoptosis. TEM results showed that extract-treated cells had nuclear membrane which was hemispherical and the nuclear chromatin was concentrated and bundled on the inner border of karyotheca. The endoplasmic reticulum also became enlarged in the inner segment. The extract also induced G2/M phase cell cycle arrest along with loss of mitochondrial membrane potential. CONCLUSION: Achillea falcata extract induced potent antiproliferative and apoptotic effects in HeLa cells. This was accompanied by cellular shrinkage, chromatin condensation, G2/M phase cell cycle arrest and a loss of mitochondrial membrane potential in these cancer cells. PMID- 26854446 TI - Human MALAT-1 long non-coding RNA is overexpressed in cervical cancer metastasis and promotes cell proliferation, invasion and migration. AB - PURPOSE: Long non-coding RNAs (lncRNAs) have been shown to play a crucial role in the development as well as the prognosis of various human cancers, particularly in human metastasis associated lung adenocarcinoma transcript-1 (MALAT-1), which has been shown to be upregulated in some tumors. However, the role of MALAT-1 in cervical cancer (CC) is yet to be elucidated. This study aimed to establish a correlation between MALAT-1 and its role in CC progression and prognosis. METHODS: The expression of MALAT-1 was examined in tissue samples of 30 CC patients and was compared with the adjacent non-cancerous tissues. The relationship between MALAT-1 levels and clinicopathological parameters from the CC patients was analyzed. Cell migration and invasion assays were performed with quantification of the expression levels of MALAT-1 in 4 CC cell lines using RT PCR. RESULTS: Our results demonstrate that MALAT-1 is upregulated in CC. We found higher expression of MALAT-1 in all the 4 CC cell lines, especially in SiHa and ME-180 CC cell lines. After analysis of the relationship between MALAT-1 levels and clinicopathological parameters from CC patients, a robust correlation could be obtained between MALAT-1 overexpression with lymph node metastasis, tumor differentiation and clinical stage. Furthermore, the ectopic expression of MALAT 1 increased cell proliferation and contributed directly to invasion and migration. CONCLUSION: Taken together, this study suggests an indispensible role played by MALAT-1 in CC progression, which may act as a potential prognostic indicator for CC and also could be a novel potential target for diagnosis of CC. PMID- 26854447 TI - Aberrant expression profile of translationally controlled tumor protein and tumor suppressive microRNAs in cervical cancer. AB - PURPOSE: Invasive and recurrent cervical cancer accounts for major mortality among women. The activity of biomarkers in cervical cancer varies with different pathological stages. The purpose of the present study was to evaluate the expression of 2 biomarkers in cervical cancer and their possible contribution to novel therapeutic strategies. METHODS: In this study, we assessed the expression of translationally controlled tumor protein (TCTP) using immunohistochemistry and Western blot analysis. The expression pattern of miR-143 was also evaluated using Northern blot analysis. RESULTS: HeLa cells and mice were used for tumor induction. A group of mice injected with HeLa cells and incubated for 6 weeks developed initial tumor, while a different group of mice injected with HeLa cells and incubated for about 10 weeks developed advanced stage cervical cancer. Histological analysis revealed higher proliferation of cells resulting in complex forms of tumor in advanced cervical cancer, whereas cell clustering was not found to be initiated in the initial stage. The results of immunohistochemistry and Western blot analysis indicated less variation in the expression of TCTP, but significant difference was observed in advanced stage. Expression of Bax apoptotic protein was higher in the initial stage of the tumor than in the advanced cervical cancer. Similar pattern of marginal downregulation of miR-143 was observed between control and initial tumor stages, but striking reduction in miR-143 expression was observed in advanced stages of tumor development. CONCLUSION: The results of this study reveal a new aspect of altered expression of biomarkers in different pathological stages that could help identify novel therapeutic strategies for cervical cancer treatment. PMID- 26854448 TI - Combination treatment with antiEGFR monoclonal antibodies in advanced nasopharyngeal carcinoma : a meta-analysis. AB - PURPOSE: The objective of this study was to compare the efficacy of the conventional treatment (radiotherapy/RT and chemotherapy/CT) and the combination treatment with antiepidermal growth factor receptor (anti EGFR) monoclonal antibodies in patients with primary nasopharyngeal cancer (NPC) using meta analysis of data retrieved from the literature. METHODS: Seven databases (Pubmed, Embase, Cochrane Library, CBM, CNKI, Wanfang,VIP) were searched. Of 537 identified articles, 12 satisfied our eligibility criteria and entered this meta analysis. A total of 821 patients in 12 randomized controlled clinical trials (RCTs) were included in the study to compare the effect in the short-term and long-term treatment. RESULTS: The combination treatment improved the objective complete remission rate (CR) of primary NPC and the metastatic lymph nodes, and the 1-year distant metastasis-free survival (MFS) rate relative risk (RR=1.40, 95%CI:1.29-1.53, p=0.00; RR=1.29, 95%CI:1.18-1.42, p=0.00; RR%1.17, 95%CI:1.01 1.35, p=0.03, respectively). There was no difference in the 2- and 3-year MFS rate (RR=1.06, 95%CI:0.85-1.33, p=0.60 ; RR=0.87, 95%CI:0.63-1.22) p=0.43, respectively). CONCLUSION: The combination with anti EGFR monoclonal antibodies and conventional treatment (RT and/or CT) improved the short-term therapeutic effect, but this benefit disappeared after 1 year. PMID- 26854449 TI - Essential oil of Cinnamon exerts anti-cancer activity against head and neck squamous cell carcinoma via attenuating epidermal growth factor receptor - tyrosine kinase. AB - PURPOSE: Impressed by the exceptional anticancer activity of cinnamon, the present study was conducted to elucidate the anticancer potential of essential oil of Cinnamon (EOC). METHODS: EOC was tested against various cell lines (FaDu, Detroit-562 and SCC-25) of head and neck squamous cell carcinoma (HNSCC) using MTT assay. The Hep-2 cell xenograft model was used to assess the positive bio activity of EOC. EGFR-TK inhibitory assay was also carried out to explain the possible mechanism of action of EOC. Moreover, to rationalise the key contacts responsible for attenuating EGFR, the major component of EOC, i.e., trans cinnamaldehyde, as identified by GC-MS analysis, was subjected to molecular docking experiments with the catalytic domain of EGFR protein model. RESULTS: EOC exhibited significant anticancer activity with percent inhibition 66.12, 87.32, and 99.34%, against FaDu, Detroit-562 and SCC-25, respectively. Moreover, EOC reduced the tumor burden to 43.5% in Hep-2 cell xenograft model along with 89% inhibition of EGFR-TK activity in the EGFR-TK inhibitory assay. Docking experiments showed that trans-cinnamaldehyde was proficiently fitted into the inner grove of the active site of EGFR by making close inter-atomic contacts with the key catalytic residues Val702, Ala719, Lys721, Leu764, Thr766 and Leu820 and with inhibition constant Ki = 775.93 MUM. CONCLUSION: EOC exhibits significant anticancer activity against HNSCC cells in vitro. The mechanism underlying its anticancer action was attributed to the suppression of EGFR-TK. It also significantly suppressed the tumor growth in Hep-2 cell xenograft model. PMID- 26854450 TI - A retrospective comparison of early stage primary extranodal with nodal non Hodgkin lymphoma patients: A single center experience. AB - PURPOSE: The primary extranodal non Hodgkin's lymphoma 'EN-NHL) is a heterogeneous group of diseases with expression of different oncogenes compared to nodal NHLs. In this study, we aimed to compare the clinical and pathological findings, the prognostic factors, the treatment and the survival data in patients with stage I-II primary EN-NHL with nodal NHL 'N-NHL). METHODS: Between January 1991 and January 2014, 853 patients with diagnosis of NHL were reviewed. Of 853 patients, 379 '44%) with stage I-II disease were included in the study and were divided into two groups according to involved sites as nodal and extranodal. The N-NHL group consisted of stage I-II patients without extranodal involvement, who were diagnosed by incisional or excisional lymph node biopsy. The EN-NHL group consisted of patients with a single primary extranodal involvement and/or a locoregional lymph node involvement, and who were diagnosed by means of a biopsy from the extranodal region. RESULTS: A total of 112 patients with N-NHL and 267 with EN-NHL were enrolled in the study. About 3/4 of the N-NHL patients had stage II, while 50% of the EN-NHL patients had stage I 'p<0.01). There was no statistically significant difference between EN-NHL and NHL in terms of 5-year overall survival '0S) 'p=0.25). The median 5-year OS in the diffuse large B cell lymphoma 'DLBCL) subgroup with N-NHL was 52%, while that of the EN-NHL was 68% 'p=0.006). CONCLUSION: Patients with stage I-II N-NHL had a poorer prognosis than EN-NHL patients. However, 5-year OS rates were similiar between groups. PMID- 26854451 TI - Methylenetetrahydrofolate reductase gene polymorphism and risk of chronic myelogenous leukemia: a meta-analysis. AB - PURPOSE: Reported evidence supports a role for methylenetetrahydrofolate reductase (MTHFR) in the risk of chronic myelogenous leykemia (CML). However, these reports arrived at non-conclusive and even conflicting results regarding the association between two common MTHFR polymorphisms (C677T and A1298C) and CML risk. Thus, a meta-analysis was carried out to clarify a more precise association between these two polymorphisms and the CML risk by updating the available publications. METHODS: Pooled odds ratios (OR) with corresponding 95% confidence interval (95% CI) and stratification analysis were performed to estimate the relationship between MTHFR polymorphisms and the risk of CML under different genetic comparison models. RESULTS: Data from the meta-analysis showed no significant association between MTHFR C677T polymorphism and CML risk. However, significant associations were found between MTHFR A1298C variants and CML risk under homozygous comparison model (CC vs AA, OR=1.62, 95% CI=1.11-2.36, p=0.01) and dominant comparison model (CC+AC vs AA, OR=1.68, 95% CI=1.17-2.43, p=0.005) in overall population; especially more obvious impacts were noticed for Asian populations in subgroup analysis for homozygous model (CC vs AA, OR=2.00, 95% CI=1.25-3.21, p=0.004) and dominant model (CC+AC vs AA, OR=2.49, 95% CI=1.42 4.36, p=0.001), but this did not apply in Caucasian populations. CONCLUSION: The results of this meta-analysis suggested no significant association between MTHFR C677T polymorphism and CML risk, while an increased CML risk was noticed for 1298C variant carriers, especially in Asian populations but not in Caucasian populations, which suggested ethnicity differences between MTHFR A1298C polymorphisms and risk of CML. PMID- 26854452 TI - Flax seed oil inhibits metastatic melanoma and reduces lung tumor formation in mice. AB - PURPOSE: Cancer is one of the leading causes of mortality worldwide. Tumor cells circulating in the blood evidence the migration of tumor from the site of origin to another site leading to the formation of new metastatic lesion and establishment of metastatic tumors. In the present study, cultured metastatic tumor cells were injected into the C57BL/6 mice through tail-vein injection (TVI) and the anti-metastatic properties of flax seed oil (FSO) were evaluated. METHODS: Pre-administration of FSO in a dose of 0.3 ml/mice/day was performed for 15 days. On 16th and 21st day, mice were challenged with 2x105 /100 MUl murine B10 melanoma (YAC-1 suspended in sterile PBS) cells and continued with FSO administration until the end of the experimental period (40 days) to assess the effect on lung metastasis. At the end of experimental period, mice were sacrificed for plasma and lung tissue samples for biochemical and marker studies. Activities of marker enzymes (AST and ALT), enzymic antioxidants (superoxide dismutase/SOD and catalase/CAT), levels of non/enzymic antioxidants (glutathione), oxidation/stress marker (malondialdehyde/MDA) and cytokines (TNF alpha, IL-2, IFN-gamma and MMP-9) were assessed. RESULTS: Elevated marker enzyme activities in serum and altered enzymic and non-enzymic antioxidants were recovered during FSO treatment. Altered metastatic markers levels favoring the formation of metastatic lesions were observed in the disease group. FSO administration re-altered the levels of these markers in the treatment group contributing to better control of metastasis development. CONCLUSION: These results support the protective role of FSO against lung cancer metastasis. PMID- 26854453 TI - Small interfering RNA (siRNA)-mediated knockdown of Notch1 suppresses tumor growth and enhances the effect of IL-2 immunotherapy in malignant melanoma. AB - PURPOSE: Malignant melanoma (MM) is a highly aggressive neoplasm that is resistant to conventional therapies. In this study, we aimed to investigate the effects of antitumor and immune enhancement of Notch1 knockdown on MM. METHODS: Mouse melanoma cells B16F1 were transfected with a small interfering RNA (siRNA) targeting Notch1 (siNotch1). RESULTS: The expression of Notch1 and its downstream hey1 was significantly decreased, resulting in reduced cell proliferation in vitro. Furthermore, intratumoral injection of siNotch1 successfully inhibited the expression of Notch1 and hey1, which suppressed tumor growth, and increased the number of tumor-infiltrating CD8+ T lymphocytes and IFN-gamma secretion in vivo, especially when combined with IL-2 immunotherapy. CONCLUSION: These results suggested that siRNA-mediated Notch1 knockdown might be an effective method for the inhibition of tumor growth both in vivo and in vitro, and might potentially enhance the effect of IL-2 immunotherapy in MM. Notch1 knockdown concurrently administered with IL-2 might be a novel therapeutic approach for the treatment of MM. PMID- 26854454 TI - Genome-wide pathway analysis in pancreatic cancer. AB - PURPOSE: The purpose of this study was to identify candidate single-nucleotide polymorphisms (SNPs) that might play a role in susceptibility to pancreatic cancer, elucidate their potential mechanisms, and generate SNP-to-gene-to-pathway hypotheses. METHODS: A genome-wide association study (GWAS) dataset of pancreatic cancer that included 496,959 SNPs from 3,851 pancreatic cancer patients and 3,934 control subjects of European descent was used in this study. The Identify candidate Causal SNPs and Pathways (ICSNPathway) method was applied to the GWAS dataset. RESULTS: ICSNPathway analysis identified 18 candidate SNPs, 11 genes (including HNF1A and HNF4G), and 30 pathways, which revealed 11 hypothetical biological mechanisms. The strongest hypothetical biological mechanism was one wherein rs2230739 alters the role of ADCY9 in various pathways and processes, including cyclase activity, phosphorus oxygen lyase activity, hsa04912, hsa04540, hsa04020, and hsa00230 (0.010 <= p < 0.001; 0.038 <= false discovery rate (FDR) <= 0.016). The second strongest mechanism was that rs16859886 modulates ADCY10 to affect its role in pathways including cyclase activity, phosphorus oxygen lyase activity, nucleobase, nucleoside, and nucleotide metabolic processing, and hsa00230 (0.010 <= p < 0.001; 0.038 <= FDR <= 0.016). CONCLUSIONS: By using the ICSNPathway to analyze pancreatic cancer GWAS data, 18 candidate SNPs, 11 genes (including ADCY9, ADCY10, HNF1A, and HNF4G), and 30 pathways were identified that might contribute to the susceptibility of patients to pancreatic cancer. PMID- 26854455 TI - Weight loss at the time of diagnosis is not associated with prognosis in patients with advanced-stage non-small cell lung cancer. AB - PURPOSE: To investigate the prognostic value of weight loss before diagnosis in patients with advanced stage non-small cell lung cancer (NSCLC) treated with first-line chemotherapy. METHODS: A total of 81 NSCLC patients with stages IIIB/IV were included in this retrospective cross-sectional study. Study variables were weight loss in the last 3 months before diagnosis, patient demographic, clinical and laboratory characteristics and histological features of the tumor before administering first-line chemotherapy. Then, the patients were stratified into 4 groups based on their weight loss before being diagnosed with NSCLC. RESULTS: The patients were predominantly male (68%), with a smoking history (62%), 5 to 10 kg weight loss in the last 3 months (31%), and had metastatic disease (64%) and adenocarcinoma (40%) at the time of diagnosis. On the other hand, most of the patients with 5 to 10 kg weight loss in the last 3 months before diagnosis had squamous cell carcinoma (44%), stage IV disease (56%), and the first disease progression was in the brain (64%). Pre-diagnosis weight loss had a negative impact on progression-free survival (PFS), independent from weight loss during first-line chemotherapy, but no such effect was noticed on overall survival (OS). CONCLUSIONS: Pre-diagnosis weight loss was found to have a negative impact on PFS in patients with NSCLC treated by first-line chemotherapy. Similar studies in larger patient series are warranted. PMID- 26854456 TI - Very long-term outcomes of minimally invasive esophagectomy for esophageal squamous cell carcinoma. AB - PURPOSE: The most critical parameter in the evaluation of the effectiveness of minimally invasive esophagectomy for esophageal squamous cell carcinoma (SCC) is long-term outcome. In this study, patients in whom more than 5 years had elapsed since they had undergone minimally invasive esophagectomy for esophageal SCC were identified, and the 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were evaluated as the long-term outcomes. METHODS: The stage, histology, perioperative complications, recurrence, and survival data were carefully reviewed in 49 patients who underwent minimally invasive esophagectomy for esophageal SCC between January 2008 and January 2010. RESULTS: Postoperative 30-day complications were observed in 12 (24.5%) patients. There was no postoperative 30-day mortality. Recurrence was observed in 26 patients (53.1%): of these, 9 (18.4%) developed local recurrence and 14 (28.6%) distant metastasis. Three patients (6.1%) had both local and distant metastases. During the study period, there were 22 (44.9%) deaths, of which 20 were due to cancer and 2 were due to other causes. The patient 5-year OS and DFS rates were 58 and 45%, respectively. CONCLUSION: Minimally invasive esophagectomy for the treatment of esophageal SCC is as feasible and safe as open esophagectomy in terms of both very long- and short-term outcomes. PMID- 26854457 TI - Anticancer effects of bishydroxycoumarin are mediated through apoptosis induction, cell migration inhibition and cell cycle arrest in human glioma cells. AB - PURPOSE: To evaluate the cytotoxic and apoptotic effects of bishydroxycoumarin (BHC) against human glioma cells and to study their mode of action. METHODS: Three cells were used in the experiments. MTT and LDH assays were used to assess the cytotoxic effects of BHC while an in vitro wound healing assay was used to study the effect of BHC on cell migration. Fluorescence microscopy and annexin V FITC assay were used to study the cellular morphology and apoptotic effects while flow cytometry in combination with propidium iodide (PI) were used to study cell cycle arrest induced by BHC. RESULTS: BHC induced substantial and dose-dependent cytotoxic effects against all three cell lines with U87MG cell line being most susceptible. BHC also inhibited cell migration and induced characteristic morphological changes including chromatin condensation, nuclear shrinkage which increased with increasing dose of BHC. The apoptotic cell population (both early and late apoptotic cells) increased with increasing dose of BHC which also induced substantial G0/G1 cell cycle growth arrest in U87MG cells. CONCLUSION: This study provides help to elucidate the translational potential of the in vitro results to be used for further in vivo studies on human glioma using animal or human subjects. The mechanistic pathway studied in this report could be helpful in explaining the mode of action of these classes of natural products. PMID- 26854458 TI - The role of the digital rectal examination as diagnostic test for prostate cancer detection in obese patients. AB - PURPOSE: Digital rectal examination (DRE) is a routine part of prostate cancer Purpose: Digital rectal examination (DRE) is a routine part of prostate cancer (PCa) screening and provides important prognostic information. The purpose of this study was to analyse the potential association between obese patients and DRE findings for PCa detection. METHODS: We retrospectively reviewed the medical records of patients who underwent an initial prostate needle biopsy for abnormal DRE, high prostate specific antigen (PSA) levels (>=4 ng/mL), or both at the Department of Urology. Patients with a history of biopsy, surgical treatment of prostatic disease, or incomplete clinical data were excluded from this study. A total of 1113 patients were included in the analysis. Before the biopsy procedure body mass index (BMI) was calculated. Age, PSA, BMI, DRE findings, prostate volume and Gleason score were analysed to assess the potential association between obesity and PCa detection. RESULTS: The mean + SD BMI was 28.3 + 4.1 kg/m2. A total of 373 (33.5%) patients were classified as obese (BMI >=30 kg/m2). No significant difference was noted in the number of biopsy cores between obese and non obese patients. The obese men were older, had a lower PSA concentration, a large prostate volume, and were less likely to have abnormal DRE findings. Patients with high grade prostate cancer (HGPCa) had higher BMI. Age, PSA and prostate volume were not significantly associated with a higher risk of cancer at biopsy. CONCLUSIONS: Our data demonstrated that obese patients have lower PSA levels, larger prostates and abundant perirectal fat. Lower PSA serum levels and large prostate size associated with high BMI, indicated a potential risk for delayed diagnosis and poor pathological outcomes.PCa) screening and provides important prognostic information. The purpose of this study was to analyse the potential association between obese patients and DRE findings for PCa detection. METHODS: We retrospectively reviewed the medical records of patients who underwent an initial prostate needle biopsy for abnormal DRE, high prostate specific antigen (PSA) levels (>=4 ng/mL), or both at the Department of Urology. Patients with a history of biopsy, surgical treatment of prostatic disease, or incomplete clinical data were excluded from this study. A total of 1113 patients were included in the analysis. Before the biopsy procedure body mass index (BMI) was calculated. Age, PSA, BMI, DRE findings, prostate volume and Gleason score were analysed to assess the potential association between obesity and PCa detection. RESULTS: The mean + SD BMI was 28.3 + 4.1 kg/m(2). A total of 373 (33.5%) patients were classified as obese (BMI >=30 kg/m(2)). No significant difference was noted in the number of biopsy cores between obese and non obese patients. The obese men were older, had a lower PSA concentration, a large prostate volume, and were less likely to have abnormal DRE findings. Patients with high grade prostate cancer (HGPCa) had higher BMI. Age, PSA and prostate volume were not significantly associated with a higher risk of cancer at biopsy. CONCLUSIONS: Our data demonstrated that obese patients have lower PSA levels, larger prostates and abundant perirectal fat. Lower PSA serum levels and large prostate size associated with high BMI, indicated a potential risk for delayed diagnosis and poor pathological outcomes. PMID- 26854459 TI - Do medical oncologists and cancer patients care about treatment costs of systemic anticancer therapy? AB - PURPOSE: The incidence, and thus the economic burden of cancer are increasing rapidly with prolongation of lifespan thanks to newly-developed anticancer drugs. Globally the number of newly diagnosed cases is expected to rise to 21.4 million by the year 2030. In this survey, our purpose was to investigate the level of awareness of oncologists and cancer patients concerning the treatment costs of systemic anticancer therapy. METHODS: To this end questionnaire forms were sent via e-mails to 123 medical oncologists which were responded by 119 (96.7%) of them. RESULTS: The responders (21%) stated that they had been attentive about the treatment costs or informed (9.5%) their patients about treatment costs. Half of the informed patients were desperately surprised when they heard the treatment costs. Half of the physicians thought that informing the patients had positive effects on patients compliance to the treatment. Most (83.5%) of the physicians prescribed drugs not paid back by reimbursement, and 79.3% of them indicated that overall survival was more important in the selection of expensive drugs. Still 30.2% of them indicated that they hadn't known to perform cost-effectiveness analyses. CONCLUSION: Creating awareness about costs of different anticancer treatment modalities in the minds of oncologists and their patients will be beneficial regarding rational use of such treatment modalities. Countries with rapidly growing health expenditures, like ours, should possess and implement country-specific criteria of cost-effectiveness in daily practice which hopefull will lead to more proper use of our medical recources. PMID- 26854460 TI - Clinical value of serum cancer antigen 19-9 as a tumor screening marker among healthy individuals. AB - PURPOSE: To investigate the clinical value of serum cancer antigen 19-9 (CA 19-9) as a tumor screening marker among healthy individuals. METHODS: CA 19-9 levels were measured in 1921 healthy individuals and were compared to reference values. Analysis based on gender was also carried out. Individuals who had higher CA 19-9 values were advised to undergo imaging examinations and start follow-up. The incidence rate of tumors in these individuals and their prognoses were monitored. RESULTS: High CA 19-9 levels were found in 30 -1.5%- individuals without tumor diagnosis at that time. The overall positive detection rate was 15.62 per 1000 population; the rate was higher in males than in females -9.29 and 32.56 per 1000 population, respectively; p<0.01-. Tumors were diagnosed in 7 -0.36%)cases -6 men and 1 woman-; 6 of 30 individuals had CA 19-9 levels that were 5-fold higher than the highest reference value, without tumor specificity. CONCLUSION: CA 19-9 has a low positive rate and is non-specific; routine screening is not recommended for healthy individuals. PMID- 26854461 TI - Hypersensitivity reactions to platinum derivatives: findings of new predictive markers. AB - PURPOSE: Platinum derivatives play a very important role in cancer therapy. Despite their outstanding results in the treatment of tumors with different locations, the occurrence of hypersensitivity reactions raises issues when it comes to therapy decision, because the changing of chemotherapy line could influence the tumor's evolution. Over the years the scientific community has paid particular attention to the mechanism by which this occurs and to identification of predictive factors. The purpose of this case-control, retrospective study was to find new predictive markers for the occurrence of allergic reactions to platinum derivatives. METHODS: We identified 59 cases of allergic reactions to platinum derivatives in the Oncology Institute "Prof. Dr. Ion Chiricuta" from Cluj-Napoca city in 2013. Blood tests data were analyzed before the administration of the cycle on which the allergic reaction occurred, along with the mandatory analyses for the patients and we focused on the values of neutrophils, lymphocytes, monocytes, eosinophils and basophils. RESULTS: When these values were compared with the values of the control group (,which was made at a ratio of 1:2 or 1:3, matched for age, tumor location and chemotherapy cycle) we found that each increase of lymphocytes or doses of platinum and each drop in monocytes number increased the risk for allergic reactions to occur. CONCLUSION: These findings are of a great value for the physicians and represent a starting point for more detailed studies. PMID- 26854462 TI - Stem cells improve the quality of colonic anastomoses - A systematic review. AB - PURPOSE: Stem cells have multiple ways of differentiating and restoring healing. This feature may recommend their usage for decreasing the incidence of anastomotic fistulas in the colon in case of colorectal malignancy. METHODS: To determine whether stem cells are improving digestive healing, we performed a literature review using as Mesh terms: "anastomotic leak", "stem cells", and "colonic anastomoses", followed by an observational analysis on 3 experimental studies. RESULTS: We found that stem cells increase bursting pressure by an elevated rate of angiogenesis. In addition, the hydroxyproline content of the anastomoses is significantly increased in the stem cell group. The results concerning microscopic characteristics of digestive healing varied markedly between studies. CONCLUSIONS: These findings suggest a novel role for mesenchymal stem cells in digestive sutures on ischemic conditions. Although stem cells have shown their beneficial effect on anastomotic healing, further studies are necessary to establish the indications, the appropriate method of administration, the sampling site and the identification of substances whose combination might potentiate their angiogenic effect. PMID- 26854463 TI - Uncommon benign lesions of the adrenal glands mimicking sinister pathologies: report of 8 cases. AB - PURPOSE: To present series of patients with large rare primary lesions of the adrenal glands that were operated in our department. The initial indication for surgery was decided based on their impressive similarity to other more sinister adrenal pathologies. METHODS: The clinical records of the department and histopathology reports, covering the 1986-2015 period were assessed. Rare adrenal pathologies that preoperatively were clinically mimicking other adrenal tumors were included. RESULTS: In total, 8 patients (age range 20-75 years) with rare tumors of the adrenal glands were found. Seven patients had a preoperative indication for adrenalectomy due to the possibility of malignancy. In one patient surgery was undertaken due to the possible diagnosis of adrenal hemorrhagic cyst. Among these patients 4 had a histopathologic diagnosis of hemangiomas, one of a lymphangiomatous cyst and 3 of myelolipomas. CONCLUSION: Rare benign tumors of the adrenal glands can present as very large lesions that can be either diagnosed incidentally or due to atypical symptoms. Though unusual, they should be considered in the differential diagnostic approach of adrenal lesions, because they share common clinical and radiological characteristics with more sinister and frequent lesions such as malignant tumors and also hematomas. PMID- 26854464 TI - Chromosome 7 deregulation in non-small cell lung carcinoma molecular landscape. AB - Lung cancer exhibits an increasing incidence and a high mortality rate worldwide. Non-small cell lung carcinoma (NSCLC)constitutes the majority of patients with lung cancer (about 85% of all pathologically defined lung cancer cases). A broad spectrum of genomic imbalances, including chromosome polysomy/aneuploidy or specific gene deregulation mechanisms, such as point mutations, deletions and amplifications has been already identified in the corresponding patients, modifying their response rates to novel targeted therapeutic regimens, and affecting also their life span. Among all chromosomes, chromosome 7 seems to play a critical role in NSCLC development and progression. Aberrations in significant genes located on it, such as EGFR, cMET, BRAF combined with numerical abnormalities of the whole chromosome are cytogenetic events that lead to specific molecular signatures in patients with NSCLC. Detection of these chromosome/gene imbalances based on polymerase chain reaction (PCR) and in situ hybridization provides to oncologists the right genetic substrate for handling these patients in a rational therapeutic way regarding their isolated molecular profile. In the current paper, we present the structural and functional profile of chromosome 7 focused on its alterations in NSCLC. PMID- 26854465 TI - Insomnia caused by aromatase inhibitors; a therapeutic challenge in patients with breast cancer. PMID- 26854466 TI - Ductal component - need for personalized follow-up after radical prostatectomy. PMID- 26854467 TI - Delayed severe thrombocytopenia due to Ipilimumab. PMID- 26854468 TI - George N. Papanicolaou (1883-1962): studying his first published article in Science 100 years on. PMID- 26854469 TI - Disulfide subproteome alterations in the platelets of patients with myelodysplastic syndrome. PMID- 26854470 TI - Uterine cancer in the writings of Byzantine physicians. AB - Byzantine physicians recognized uterine cancer as a distinct disease and tried to suggest a therapeutic approach. The work of Oribasius, Aetius of Amida, Paul of Aegina, Cleopatra Metrodora and Theophanes Nonnus reflects the Hippocratic Galenic scientific ideas as well as their own concept on this malignancy. According to their writings uterine cancer was considered an incurable disease and its treatment was based mainly on palliative herbal drugs. PMID- 26854471 TI - Gemcitabine and Capecitabine Combination Chemotherapy in Patients with Metastatic Breast Cancer Pretreated with Anthracyclines and/or Taxanes. AB - BACKGROUND: Owing to the need for effective and tolerable new regimens for the treatment of patients with metastatic breast cancer (MBC) previously treated with anthracyclines and/or taxanes, we aimed to assess the activity and safety of the gemcitabine plus capecitabine combination chemotherapy. METHODS: Sixty-four patients were enrolled. Treatment consisted of gemcitabine 1,000 mg/m2 intravenously on days 1 and 8, plus oral capecitabine at 1,250 mg/m2 twice daily on days 1-14. The primary end point was the overall response rate (ORR). Secondary objectives included the disease control rate (DCR), overall survival (OS), progression-free survival (PFS), toxicity, and predictive factors. RESULTS: In the 64 patients, the ORR and DCR was 28.1 and 67.2%. Median OS and PFS were 23.6 and 13.4 months, respectively. Toxicities were mild and curable. CONCLUSION: The combination of gemcitabine and capecitabine is an effective and tolerable treatment for MBC previously treated with anthracyclines and/or taxanes. PMID- 26854472 TI - Detailed Surgical Anatomy of Prostate: Relationship between Urethra and Dorsal Vein Complex with Apex. AB - AIM: To describe our surgical technique for dissecting the apex of prostate during robotic-assisted laparoscopic radical prostatectomy (RALP) and detailed surgical anatomy of prostate including relationship between urethra and dorsal vein complex with apex. MATERIALS AND METHODS: In retrospective view of prospective collected data, 73 patients underwent RALP between December 2012 and September 2014. Surgical anatomy of prostate was revealed in all procedures. Quality of life (QoL) scores were assessed before, immediately after catheter removal, and 1 month after surgery. We divided urinary continence into 3 groups, as very early continence; continence at time of urethral catheter removal, early continent; and continence 1 month after surgery. The rest of the patients were accepted as continence. RESULTS: The mean follow-up was 10.2 +/- 5.4 months and mean age was 61.5 +/- 6.6. Maximum protection of urethra could be provided in all. Mean catheter removal was 8.9 +/- 1.7 days, and all patients were continent at the time of catheter removal. QoL scores before RALP could be protected after surgery (p = 0.2). Neither conversion to open/conventional laparoscopic surgery nor complications related with bladder neck were detected. CONCLUSIONS: Our surgical technique can be a strong candidate for being a surgical technique for preserving urethra and very early continence could be provided after surgery. PMID- 26854473 TI - Cardiovascular and Cognitive Health Study in Middle-Aged and Elderly Residents of Beijing(CCHS-Beijing): Design and Rationale. AB - The Cardiovascular and Cognitive Health Study (CCHS-Beijing) is a population based study of cardiovascular disease (CVD) and cognitive impairment in adults aged 55 and older in Beijing. The main aims of the study are to investigate the prevalence rates of CVD, asymptomatic atherosclerosis, and cognitive impairment, as well as validate the risk factors related to the onset and development of CVD, Alzheimer's disease (AD) and mild cognitive impairment (MCI). The study was designed to detect the traditional and new risk factors in this age group. Participants were recruited randomly from residential regions in the greater Beijing municipality area based on the average levels of development in Beijing, China in 2012 (based on socioeconomic, demographic, and geographical characteristics). Thorough physical and laboratory examination were performed at baseline (also the cross-sectional survey) to identify the risk factors such as hypertension, dyslipidemia, diabetes, as well as newly defined risk factors like elevated homocysteine, high sensitivity C-reactive protein, and urine micro albumin. Subclinical disease of the cerebral vasculature included atherosclerosis of carotid arteries, intracranial arteries, and retinal vessels. Subclinical cardiac diseases included left ventricular enlargement, arrhythmias, chamber hypertrophy and myocardial ischemia. Blood pressure was documented using the ankle-arm method. In addition, neuropsychological assessments were performed for all subjects aged 65 and above. Baseline evaluation began during the period August 2013 to December 2014. Follow-up examination will occur in 5 years. The initial and recurrent CVD, AD and MCI events will be verified and validated during the follow-up period. PMID- 26854474 TI - A methodology for markerless genetic modifications in Azotobacter vinelandii. AB - AIMS: Efficient manipulation of multiple regions within a genome can be improved by counter-selection approaches. In this work, we sought to develop a method to manipulate Azotobacter vinelandii using a counter-selection approach based on the presence of the pyrF gene. METHODS AND RESULTS: A background uracil auxotroph of A. vinelandii was first constructed by deleting the pyrF gene coding orotidine-5' phosphate decarboxylase. The pyrF gene and promoter were also incorporated together with an antibiotic marker to create a selection and counter-selection cassette to shuttle into various plasmids. The constructed cassette could then be removed using a plasmid lacking the pyrF gene via counter-selection resulting from the production of 5-fluorouracil. The process could be repeated multiple times using the same procedure for selection and counter-selection. Following completion, the pyrF gene may be reintroduced to the genome in its original location, leaving a completed strain devoid of any antibiotic markers. CONCLUSIONS: Utilization of the pyrF gene for counter-selection is a powerful tool that can be used effectively to make multiple gene deletions in A. vinelandii. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the successful application of a counter-selection approach to yield markerless genetic modifications to A. vinelandii, which should be of interest for a range of applications in this important model bacterium. PMID- 26854475 TI - Impact of EGF, IL28B, and PNPLA3 polymorphisms on the outcome of allograft hepatitis C: a multicenter study. AB - Hepatitis C virus (HCV) infection is accelerated following liver transplantation (LT). Single nucleotide polymorphisms (SNPs) near the epidermal growth factor (EGF) (rs4444903), IL28B (rs12979860), and PNPLA3 (rs738409) loci are associated with treatment response, fibrosis, and hepatocellular carcinoma in non-transplant hepatitis C, but allograft population data are limited. We sought to determine the role of these SNPs in 264 patients with HCV who underwent LT between 1990 and 2008. Genotypes were determined from donor wedge/allograft biopsies and recipient explants. Cox proportional hazards model was used to assess time to cirrhosis, liver-related death, and retransplantation, adjusting for donor age and sustained virological response (SVR). Over a median follow-up of 6.3 yr, a trend toward increased progression to graft cirrhosis was observed among recipients of an EGF non-AA vs. AA donor liver (adjusted HR 2.01; 95% CI 0.93-4.34; p = 0.08). No other genotypes predicted cirrhosis development or graft survival. The CC IL28B variant in both recipients and donors was associated with increased rate of SVR (R-CC/D-CC 8/12[67%], R-non-CC/D-CC or R-CC/D-non-CC 23/52[44%], R-non-CC/D-non CC 12/45[27%], p linear trend = 0.009). Recipient EGF, IL28B, and PNPLA3, and donor IL28B and PNPLA3 genotypes do not predict adverse outcomes in HCV LT recipients. A potential association exists between donor EGF genotype and cirrhosis. PMID- 26854477 TI - Fast search of thousands of short-read sequencing experiments. AB - The amount of sequence information in public repositories is growing at a rapid rate. Although these data are likely to contain clinically important information that has not yet been uncovered, our ability to effectively mine these repositories is limited. Here we introduce Sequence Bloom Trees (SBTs), a method for querying thousands of short-read sequencing experiments by sequence, 162 times faster than existing approaches. The approach searches large data archives for all experiments that involve a given sequence. We use SBTs to search 2,652 human blood, breast and brain RNA-seq experiments for all 214,293 known transcripts in under 4 days using less than 239 MB of RAM and a single CPU. Searching sequence archives at this scale and in this time frame is currently not possible using existing tools. PMID- 26854478 TI - EFFECTIVENESS OF DIALECTICAL BEHAVIOR THERAPY VERSUS COLLABORATIVE ASSESSMENT AND MANAGEMENT OF SUICIDALITY TREATMENT FOR REDUCTION OF SELF-HARM IN ADULTS WITH BORDERLINE PERSONALITY TRAITS AND DISORDER-A RANDOMIZED OBSERVER-BLINDED CLINICAL TRIAL. AB - BACKGROUND: Many psychological treatments have shown effect on reducing self-harm in adults with borderline personality disorder. There is a need of brief psychotherapeutical treatment alternative for suicide prevention in specialized outpatient clinics. METHODS/DESIGN: The DiaS trial was designed as a pragmatic single-center, two-armed, parallel-group observer-blinded, randomized clinical superiority trial. The participants had at least two criteria from the borderline personality disorder diagnosis and a recent suicide attempt (within a month). The participants were offered 16 weeks of dialectical behavior therapy (DBT) versus up to 16 weeks of collaborative assessment and management of suicidality (CAMS) treatment. The primary composite outcome was the number of participants with a new self-harm (nonsuicidal self-injury [NSSI] or suicide attempt) at week 28 from baseline. Other exploratory outcomes were: severity of borderline symptoms, depressive symptoms, hopelessness, suicide ideation, and self-esteem. RESULTS: At 28 weeks, the number of participants with new self-harm in the DBT group was 21 of 57 (36.8%) versus 12 of 51 (23.5%) in the CAMS treatment (OR: 1.90; 95% CI: 0.80-4.40; P = .14). When assessing the effect of DBT versus CAMS treatment on the individual components of the primary outcome, we observed no significant differences in the number of NSSI (OR: 1.60; 95% CI: 0.70-3.90; P = .31) or number of attempted suicides (OR: 2.24; 95% CI: 0.80-7.50; P = .12). CONCLUSION: In adults with borderline personality traits and disorder and a recent suicide attempt, DBT does not seem superior compared with CAMS for reduction of number of self-harm or suicide attempts. However, further randomized clinical trials may be needed. PMID- 26854479 TI - Use and effectiveness of quitlines versus Web-based tobacco cessation interventions among 4 state tobacco control programs. AB - BACKGROUND: Comparative effectiveness studies of state tobacco quitlines and Web based tobacco cessation interventions are limited. In 2009, the US Centers for Disease Control and Prevention undertook a study of the comparative effectiveness of state quitlines and Web-based tobacco cessation interventions. METHODS: Standardized questionnaires were administered to smokers who enrolled exclusively in either quitlines or Web-based tobacco cessation services in 4 states in 2011 2012. The primary outcome was the 30-day point prevalence abstinence (PPA) rate at 7 months both between and within interventions. RESULTS: A total of 4086 participants were included in the analysis. Quitline users were significantly older, more heterogeneous in terms of race and ethnicity, less educated, less likely to be employed, and more often single than Web-based users. The 7-month 30 day PPA rate was 32% for quitline users and 27% for Web-based users. Multivariate models comparing 30-day PPA rates between interventions indicated that significantly increased odds of quitting were associated with being partnered, not living with another smoker, low baseline cigarette use, and more interactions with the intervention. After adjustments for demographic and tobacco use characteristics, quitline users had 1.26 the odds of being abstinent in comparison with Web-based users (95% confidence interval, 1.00-1.58; P = .053). CONCLUSIONS: This is one of the largest comparative effectiveness studies of state tobacco cessation interventions to date. These findings will help public health agencies develop and tailor evidence-based tobacco cessation programs. Further research should focus on users of Web-based cessation interventions sponsored by state health departments and their cost-effectiveness. PMID- 26854476 TI - Minimally invasive endovascular stent-electrode array for high-fidelity, chronic recordings of cortical neural activity. AB - High-fidelity intracranial electrode arrays for recording and stimulating brain activity have facilitated major advances in the treatment of neurological conditions over the past decade. Traditional arrays require direct implantation into the brain via open craniotomy, which can lead to inflammatory tissue responses, necessitating development of minimally invasive approaches that avoid brain trauma. Here we demonstrate the feasibility of chronically recording brain activity from within a vein using a passive stent-electrode recording array (stentrode). We achieved implantation into a superficial cortical vein overlying the motor cortex via catheter angiography and demonstrate neural recordings in freely moving sheep for up to 190 d. Spectral content and bandwidth of vascular electrocorticography were comparable to those of recordings from epidural surface arrays. Venous internal lumen patency was maintained for the duration of implantation. Stentrodes may have wide ranging applications as a neural interface for treatment of a range of neurological conditions. PMID- 26854480 TI - [Expression of EphA2 in Metastatic and Non-Metastatic Primary Uveal Melanoma]. AB - BACKGROUND: Little is known about how the expression of Ephrin type-A receptor 2 (EphA2) influences cell-cell adhesion, migration, angiogenesis, and the formation of vasculogenic mimicry (VM) channels in uveal melanomas or how this may be related to the rate of metastasis. MATERIAL AND METHODS: Paraffin embedded sections of 50 histopathologically well characterised primary uveal melanomas (mean largest tumour diameter: 16.3 mm) were evaluated with respect to the expression of EphA2. Systemic metastasis was detected in 29 patients. The remaining 21 patients were followed for a mean of 10 years. Tumour angiogensis was analysed by endoglin expression (CD105), the activity of the mature vascular system (von Willebrand factor) and the presence of VM (CD31/PAS staining). RESULTS: All uveal melanomas expressed EphA2, with a mean of 95.93 % positive cells +/- SD: 6.3 %. There was no significant association between EphA2 and the rate of metastases (p = 0.196), endoglin expression (p = 0.652), VM (p = 0.267) or with any other clinical or histopathological factors (p < 0.05). However, there was significant up-regulation of EphA2 in the nucleus of the metastatic uveal melanoma subgroup, while cytoplasmatic localisation in the subgroup was associated with better prognosis (p = 0.006). There were low levels of EphA2 expression in the specific retinal layers, the ciliary and corneal epithelium, and the choroidal and corneal endothelium. CONCLUSION: Nuclear expression of EphA2 in this series of large tumours was significantly associated with an increased rate of metastasis. On the other hand, cytoplasmic localisation was associated with a better prognosis. As there was no correlation between EphA2 expression and angiogenesis, the mature vasculature or VM, EphA2 appears to become less important in the advanced stages of the disease. PMID- 26854481 TI - [Long-term Outcomes and Complications after Surgical Posterior Capsule Polishing Due to Secondary Cataract]. AB - BACKGROUND: To evaluate the long-term outcome and complication rate after surgical posterior capsule polishing as an alternative to Nd : YAG-Laser posterior capsulotomy in the treatment of posterior capsule opacity after cataract extraction in eyes with high risk of developing pseudophakic retinal detachment. PATIENTS AND METHODS: This retrospective study comprised 265 eyes in 234 patients (134 women, 100 men, mean age: 61 years) with posterior capsule opacity who underwent surgical posterior capsule polishing between 1997 and 2010, with a follow-up of at least 12 months. RESULTS: Surgical posterior capsule polishing was performed in 220 myopic eyes (axial length > 25 mm), in 28 eyes after retinal detachment surgery and in 17 eyes with traumatic cataract. The mean follow-up was 73 months (range: 12 to 202 months); in 206 eyes (77.8 %), follow up was more than 3 years. The final best-corrected visual acuity (BCVA) in logMAR (mean 0.56 +/- 0.63) improved significantly (p < 0.001) compared to the preoperative BCVA (mean 0.93 +/- 0.72). Recurrent posterior capsule opacity occurred in 74 eyes (27.9 %) and was treated by one or more surgical posterior capsule polishing procedures. Nd : YAG-Laser posterior capsulotomy was performed in 28 eyes (10.6 %) and surgical capsulectomy in 8 eyes (3.0 %). Complications after surgical posterior capsule polishing included intraoperative capsule rupture in 9 eyes (3.5 %). No postoperative endophthalmitis was observed. However, retinal detachment occurred in 6 eyes (2.3 %) 62 months after surgical posterior capsule polishing. All eyes were myopic (axial length > 25 mm) and initially vitrectomised during first retinal detachment surgery. CONCLUSIONS: Long-term outcome and complication rate indicate that surgical posterior capsule polishing is not only a more complex procedure but is also associated with a higher relapse risk than Nd : YAG-Laser posterior capsulotomy in the treatment of regenerative secondary cataract. Furthermore, conserving the posterior lens capsule does not always seem to minimise the cumulative risk of developing pseudophakic retinal detachment in high risk patients. PMID- 26854482 TI - [Morphologic Patterns on Spectral-Domain Optical Coherence Tomography (SD-OCT) as a Prognostic Indicator in Treatment of Macular Edema Due to Retinal Vein Occlusion]. AB - BACKGROUND: SD-OCT is an important tool in the diagnosis of macular oedema (ME) due to retinal vein occlusion (RVO). Its high resolution makes it possible to distinguish various morphological characteristics and differences. The aim of this study is to evaluate the correlation between morphological patterns and the development of visual acuity (VA) after intravitreal treatment of ME due to RVO. METHODS: 81 patients on intravitreal treatment (dexamethasone: n = 53/ranibizumab: n = 28) due to ME associated with branch and central retinal vein occlusion ( BRVO: n = 38/CRVO: n = 43) were retrospectively reviewed. Preoperative SD-OCT images were analysed by vitreous adhesion, epiretinal membranes, foveal contour, height of intraretinal cystoid spaces, inner and outer segment integrity and presence of subretinal fluid. The influence of these patterns on VA improvement was analysed. RESULTS: In almost every morphological pattern, the data were highly variable. Therapy was effective, with a medium gain in VA of 9.51 letters ETDRS (dexamethasone: 9.62 letters/ranibizumab: 9.29 letters). The improvement in VA in patients with small intraretinal cystoid spaces (thickness <= 250 um) was 19.44 letters ETDRS, compared to 7.23 letters ETDRS in patients with confluent cystoid spaces (p = 0.009). Patients with a convex fovea exhibited more pronounced reduction in central retinal thickness (CRT) (p = 0.004). CONCLUSION: Analysis of OCT has concentrated on demonstrating oedema and CRT. Our data indicate that detailed OCT morphology and the size of intraretinal cystoid spaces offer important information about VA prognosis after intravitreal therapy in ME due to RVO. PMID- 26854483 TI - [Evaluation of the Global Research Architecture Regarding Diabetic Retinopathy]. AB - Aims and Scope: Diabetic retinopathy (DR) is of major scientific and socioeconomic interest in most of the industrialized countries due to increasing prevalence. This interest is reflected by a marked increase in the number of publications since the 1990 s. It is therefore difficult for a single author to obtain an overview of the topic. Material and Methods: The total number of published items on DR was determined in the Web of Science database. All bibliometric data were collected for the period 1900 to 2008 (search term:"diabet* retinopath*" and "diabet* macul*"). A number of different scientometric methods were applied in accordance with the NewQIS protocol, e.g. state of the art visualisation techniques such as density equalising maps and network diagrams. Results: A total of 15,624 publications were identified. The U. S. A. leads in the overall number of publications (4,689). The most productive and the most prolific institutions, authors and publications are all in the U. S. A. The University of Wisconsin (i.e. Ronald Klein and his wife Barbara Eden Kobrin Klein) have established an international network with a large number of institutions publishing important work. Nevertheless, many other important institutions can be identified, e.g. the Joslin Diabetes Center, which has published many articles on VEGF. Conclusion: The results reveal that the scientific interest on the topic DR is continuously increasing. International collaboration is of growing importance in this field. PMID- 26854484 TI - High miR-34a expression improves response to doxorubicin in diffuse large B-cell lymphoma. AB - The standard treatment for patients with diffuse large B-cell lymphoma (DLBCL) is the immunochemotherapy-based R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). Resistance to treatment, intrinsic or acquired, is observed in approximately 40% of patients with DLBCL, who thus require novel interventions to survive. To identify biomarkers for cytotoxic response assessment, microRNAs (miRNAs) associated with doxorubicin sensitivity were determined by combining global miRNA expression profiling with systematic dose-response screens in 15 human DLBCL cell lines. One candidate, miR-34a, was tested in functional in vitro studies and in vivo in a retrospective clinical cohort. High expression of miR-34a was observed in cell lines sensitive to doxorubicin, and upregulation of miR-34a is documented here to increase doxorubicin sensitivity in in vitro lentiviral transduction assays. High expression of miR-34a had a prognostic impact using overall survival as outcome. With risk stratification of DLBCL samples based on resistance gene signatures (REGS), doxorubicin-responsive samples had statistically significant upregulated miR-34a expression. Classification of the DLBCL samples into subset-specific B cell-associated gene signatures (BAGS) revealed differentiation-specific expression of miR-34a. Our data further support FOXP1 as a target of miR-34a, suggesting that downregulation of FOXP1 may sensitize DLBCL cells to doxorubicin. We conclude that miRNAs, in particular miR-34a, may have clinical utility in DLBCL patients as both predictive and prognostic biomarkers. PMID- 26854485 TI - Expression of the MOZ-TIF2 oncoprotein in mice represses senescence. AB - The MOZ-TIF2 translocation, which fuses monocytic leukemia zinc finger protein (MOZ) histone acetyltransferase (HAT) with the nuclear co-activator TIF2, is associated with the development of acute myeloid leukemia. We recently found that in the absence of MOZ HAT activity, p16(INK4a) transcriptional levels are significantly increased, triggering an early entrance into replicative senescence. Because oncogenic fusion proteins must bypass cellular safeguard mechanisms, such as senescence and apoptosis, to induce leukemia, we hypothesized that this repressive activity of MOZ over p16(INK4a) transcription could be preserved, or even reinforced, in MOZ leukemogenic fusion proteins, such as MOZ TIF2. We describe here that, indeed, MOZ-TIF2 silences expression of the CDKN2A locus (p16(INK4a) and p19(ARF)), inhibits the triggering of senescence and enhances proliferation, providing conditions favorable to the development of leukemia. Furthermore, we describe that abolishing the MOZ HAT activity of the fusion protein leads to a significant increase in expression of the CDKN2A locus and the number of hematopoietic progenitors undergoing senescence. Finally, we report that inhibition of senescence by MOZ-TIF2 is associated with increased apoptosis, suggesting a role for the fusion protein in p53 apoptosis-versus senescence balance. Our results underscore the importance of the HAT activity of MOZ, preserved in the fusion protein, for repression of the CDKN2A locus transcription and the subsequent block of senescence, a necessary step for the survival of leukemic cells. PMID- 26854486 TI - A Randomized-Controlled Trial of Oral Low-Dose Isotretinoin for Difficult-To Treat Papulopustular Rosacea. AB - Rosacea is a chronic inflammatory facial skin disease with psychosocial impact. Oral cyclines are recommended for moderate-to-severe papulopustular rosacea. Oral isotretinoin was found valuable for difficult-to-treat cases in several reports. This multicenter, double-blind, randomized-placebo-controlled trial compared oral isotretinoin (0.25 mg/kg/day) with placebo (2:1 ratio) for difficult-to-treat papulopustular rosacea. Included patients had at least eight papulopustular lesions. The primary endpoint after the 4-month treatment period was the response rate: at least 90% reduction of the number of papules/pustules compared with baseline. Secondary outcomes included measures on quality of life (Skindex score). Between February 2007 and August 2009, 156 patients were randomized to receive either isotretinoin (n = 108) or placebo (n = 48). In the intention-to treat population, 57.4% of isotretinoin recipients reached the primary endpoint, compared with 10.4% of those taking the placebo (absolute difference, 47 percentage points; 95% confidence interval, 34.3-59.7; P < 0.0001). To consider therapy successful, 2.1 (95% confidence interval 1.7-2.9) patients had to be treated. Skindex scores had improved significantly more for isotretinoin- than placebo-treated patients. Rosacea relapsed in 27 (58.3%) of 51 patients who accepted 4 months of continued follow-up, with a median of 15 weeks to recurrence. The percentages of patients in each arm who stopped their treatment because of adverse event(s) did not differ. Low-dose isotretinoin was an effective therapeutic option for difficult-to-treat papulopustular rosacea. Further studies should investigate the value of a minimal effective isotretinoin dose to maintain these remissions. PMID- 26854487 TI - Topical Application of Dieckol Ameliorates Atopic Dermatitis in NC/Nga Mice by Suppressing Thymic Stromal Lymphopoietin Production. PMID- 26854489 TI - Association of Vemurafenib and Pipobroman Enhances BRAF-CRAF Dimerization in Squamous Cell Carcinoma. PMID- 26854488 TI - Longitudinal Evaluation of the Skin Microbiome and Association with Microenvironment and Treatment in Canine Atopic Dermatitis. AB - Host-microbe interactions may play a fundamental role in the pathogenesis of atopic dermatitis, a chronic relapsing inflammatory skin disorder characterized by universal colonization with Staphylococcus species. To examine the relationship between epidermal barrier function and the cutaneous microbiota in atopic dermatitis, this study used a spontaneous model of canine atopic dermatitis. In a cohort of 14 dogs with canine atopic dermatitis, the skin microbiota were longitudinally evaluated with parallel assessment of skin barrier function at disease flare, during antimicrobial therapy, and post-therapy. Sequencing of the bacterial 16S ribosomal RNA gene showed decreased bacterial diversity and increased proportions of Staphylococcus (S. pseudintermedius in particular) and Corynebacterium species compared with a cohort of healthy control dogs (n = 16). Treatment restored bacterial diversity with decreased proportions of Staphylococcus species, concurrent with decreased canine atopic dermatitis severity. Skin barrier function, as measured by corneometry, pH, and transepidermal water loss also normalized with treatment. Bacterial diversity correlated with transepidermal water loss and pH level but not with corneometry results. These findings provide insights into the relationship between the cutaneous microbiome and skin barrier function in atopic dermatitis, show the impact of antimicrobial therapy on the skin microbiome, and highlight the utility of canine atopic dermatitis as a spontaneous nonrodent model of atopic dermatitis. PMID- 26854490 TI - Promoter Methylation of PTEN Is a Significant Prognostic Factor in Melanoma Survival. AB - Structural compromise of the tumor suppressor gene, phosphatase and tensin homolog (PTEN), occurs in 10% of melanoma specimens, and loss of PTEN expression through DNA methylation of the PTEN promoter region has also been reported in a number of other malignancies. However, the role of PTEN promoter methylation in melanoma is not well understood. We thus sought to elucidate the prevalence of PTEN promoter methylation in melanoma specimens, its relationship to clinical features, and its impact on the outcome of patients with melanoma. PTEN promoter methylation data were acquired from an archived primary Korean melanoma cohort (KMC) of 158 patients and, for validation, 234 patients from The Cancer Genome Atlas melanoma (TCGA-MEL) cohort. Hierarchical clustering was performed to identify PTEN "high methylated" and "low methylated" samples. Subsequently, differences in clinical features and outcomes based on PTEN promoter methylation status were then analyzed using SPSS and R. In the KMC, all tumors were acquired from primary tumors and 65.7% (n = 105) were acral or mucosal by site, whereas in the TCGA-MEL cohort, 90.5% of the tumors were from regional lymph node and distant metastatic lesions. Overall, 17.7% and 45.7% of the specimens harbored BRAF mutations in the KMC and TCGA-MEL cohort, respectively. Neuroblastoma RAS viral oncogene homolog was mutated in 12.2% and 26.9% of the tumors in the KMC and TCGA-MEL cohort, respectively. In the KMC, 31 cases (19.6%) were included in the high methylated group versus 142 cases (60.7%) in the TCGA-MEL cohort (P < 0.001). Multivariate Cox-regression analysis revealed promoter methylation of PTEN to be an independent negative prognostic factor for survival in both the KMC (hazard ratio 3.76, 95% confidence interval = 1.24-11.12, P = 0.017) and TCGA-MEL cohort (HR 1.88, 95% confidence interval = 1.13-3.12, P = 0.015). Our results indicate that PTEN promoter methylation is an independent predictor for impaired survival in patients with melanoma. PMID- 26854491 TI - Intronic ITGA3 Mutation Impacts Splicing Regulation and Causes Interstitial Lung Disease, Nephrotic Syndrome, and Epidermolysis Bullosa. PMID- 26854492 TI - Fibronectin-Containing Extracellular Vesicles Protect Melanocytes against Ultraviolet Radiation-Induced Cytotoxicity. AB - Skin melanocytes are activated by exposure to UV radiation to secrete melanin containing melanosomes to protect the skin from UV-induced damage. Despite the continuous renewal of the epidermis, the turnover rate of melanocytes is very slow, and they survive for long periods. However, the mechanisms underlying the survival of melanocytes exposed to UV radiation are not known. Here, we investigated the role of melanocyte-derived extracellular vesicles in melanocyte survival. Network analysis of the melanocyte extracellular vesicle proteome identified the extracellular matrix component fibronectin at a central node, and the release of fibronectin-containing extracellular vesicles was increased after exposure of melanocytes to UVB radiation. Using an anti-fibronectin neutralizing antibody and specific inhibitors of extracellular vesicle secretion, we demonstrated that extracellular vesicles enriched in fibronectin were involved in melanocyte survival after UVB radiation. Furthermore, we observed that in the hyperpigmented lesions of patients with melasma, the extracellular space around melanocytes contained more fibronectin compared with normal skin, suggesting that fibronectin is involved in maintaining melanocytes in pathological conditions. Collectively, our findings suggest that melanocytes secrete fibronectin containing extracellular vesicles to increase their survival after UVB radiation. These data provide important insight into how constantly stimulated melanocytes can be maintained in pathological conditions such as melasma. PMID- 26854493 TI - Oral Supplementation with Cocoa Extract Reduces UVB-Induced Wrinkles in Hairless Mouse Skin. AB - Cacao beans contain various bioactive phytochemicals that could modify the pathogeneses of certain diseases. Here, we report that oral administration of cacao powder (CP) attenuates UVB-induced skin wrinkling by the regulation of genes involved in dermal matrix production and maintenance. Transcriptome analysis revealed that 788 genes are down- or upregulated in the CP supplemented group, compared with the UVB-irradiated mouse skin controls. Among the differentially expressed genes, cathepsin G and serpin B6c play important roles in UVB-induced skin wrinkle formation. Gene regulatory network analysis also identified several candidate regulators responsible for the protective effects of CP supplementation against UVB-induced skin damage. CP also elicited antiwrinkle effects via inhibition of UVB-induced matrix metalloproteinases-1 expression in both the human skin equivalent model and human dermal fibroblasts. Inhibition of UVB-induced activator protein-1 via CP supplementation is likely to affect the expression of matrix metalloproteinases-1. CP supplementation also downregulates the expression of cathepsin G in human dermal fibroblasts. 5-(3',4' Dihydroxyphenyl)-gamma-valerolactone, a major in vivo metabolite of CP, showed effects similar to CP supplementation. These results suggest that cacao extract may offer a protective effect against photoaging by inhibiting the breakdown of dermal matrix, which leads to an overall reduction in wrinkle formation. PMID- 26854494 TI - Dynamic contrast-enhanced MRI for oncology drug development. AB - Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising tool for evaluating tumor vascularity, as it can provide vasculature-derived, functional, and quantitative parameters. To implement DCE-MRI parameters as biomarkers for monitoring the effect of antiangiogenic or vascular-disrupting treatment, two crucial elements of surrogate endpoint, ie, validation and qualification, should be satisfied. Although early studies have shown the accuracy and reliability of DCE-MRI parameters for evaluating treatment-driven vascular alterations, there have been an increasing number of studies demonstrating the limitations of DCE-MRI parameters as surrogate endpoints. Therefore, in order to improve the application of DCE-MRI parameters in drug development, it is necessary to establish a standardized evaluation method and to determine the correct therapeutics-oriented meaning of individual DCE-MRI parameter. In this regard, this article describes the biophysical background and data acquisition/analysis techniques of DCE-MRI while focusing on the validation and qualification issues. Specifically, the causes of disagreement and confusion encountered in the preclinical and clinical trials using DCE-MRI are presented in detail. Finally, considering these limitations, we present potential strategies to optimize implementation of DCE-MRI. J. Magn. Reson. Imaging 2016;44:251-264. PMID- 26854496 TI - Colonic diverticular disease: medical treatments for acute diverticulitis. AB - INTRODUCTION: Diverticula (mucosal outpouchings through the wall of the colon) are rare before the age of 40 years, after which prevalence increases steadily and reaches over 25% by 60 years. However, only 10% to 25% of affected people will develop symptoms such as lower abdominal pain. Recurrent symptoms are common, and 5% of people with diverticula eventually develop complications such as perforation, obstruction, haemorrhage, fistulae, or abscesses. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of medical treatments for acute diverticulitis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to August 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 193 studies. After deduplication and removal of conference abstracts, 75 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 37 studies and the further review of 38 full publications. Of the 38 full articles evaluated, four systematic reviews and one RCT were added at this update. We performed a GRADE evaluation for two PICO combinations CONCLUSIONS: In this systematic overview, we categorised the efficacy for one comparison based on information about the effectiveness and safety of medical treatment (mesalazine, antibiotics [any] only) versus placebo or no treatment. PMID- 26854497 TI - The extreme relativity of perception: A new contextual effect modulates human resolving power. AB - The authors report the discovery of a new effect of context that modulates human resolving power with respect to an individual stimulus. They show that the size of the difference threshold or the just noticeable difference around a standard stimulus depends on the range of the other standards tested simultaneously for resolution within the same experimental session. The larger this range, the poorer the resolving power for a given standard. The authors term this effect the range of standards effect (RSE). They establish this result both in the visual domain for the perception of linear extent, and in the somatosensory domain for the perception of weight. They discuss the contingent nature of stimulus resolution in perception and psychophysics and contrast it with the immunity to contextual influences of visually guided action. PMID- 26854498 TI - Neural dissociations in attitude strength: Distinct regions of cingulate cortex track ambivalence and certainty. AB - People's behaviors are often guided by valenced responses to objects in the environment. Beyond positive and negative evaluations, attitudes research has documented the importance of attitude strength--qualities of an attitude that enhance or attenuate its impact and durability. Although neuroscience research has extensively investigated valence, little work exists on other related variables like metacognitive judgments about one's attitudes. It remains unclear, then, whether the various indicators of attitude strength represent a single underlying neural process or whether they reflect independent processes. To examine this, we used functional MRI (fMRI) to identify the neural correlates of attitude strength. Specifically, we focus on ambivalence and certainty, which represent metacognitive judgments that people can make about their evaluations. Although often correlated, prior neuroscience research suggests that these 2 attributes may have distinct neural underpinnings. We investigate this by having participants make evaluative judgments of visually presented words while undergoing fMRI. After scanning, participants rated the degree of ambivalence and certainty they felt regarding their attitudes toward each word. We found that these 2 judgments corresponded to distinct brain regions' activity during the process of evaluation. Ambivalence corresponded to activation in anterior cingulate cortex, dorsomedial prefrontal cortex, and posterior cingulate cortex. Certainty, however, corresponded to activation in unique areas of the precuneus/posterior cingulate cortex. These results support a model treating ambivalence and certainty as distinct, though related, attitude strength variables, and we discuss implications for both attitudes and neuroscience research. PMID- 26854499 TI - Profiling of Multiple Targets of Artemisinin Activated by Hemin in Cancer Cell Proteome. AB - The antimalarial drug artemisinin is found to have diverse biological activities ranging from anti-inflammatory to anticancer properties; however, as of today, the cellular targets and mechanism of action of this important compound have remained elusive. Here, we report the global protein target profiling of artemisinin in the HeLa cancer cell proteome using a chemical proteomics approach. In the presence of hemin, multiple proteins were targeted by artemisinin probe through covalent modification. Further studies revealed that reducing of hemin to heme by protein thiols was essential for endoperoxide activation and subsequent protein alkylation. Artemisinin may exert its synergistic therapeutic anticancer effects via modulation of a variety of cellular pathways through acting on multiple targets. PMID- 26854500 TI - Metabolic Engineering of Pseudomonas putida KT2440 for Complete Mineralization of Methyl Parathion and gamma-Hexachlorocyclohexane. AB - Agricultural soils are often cocontaminated with multiple pesticides. Unfortunately, microorganisms isolated from natural environments do not possess the ability to simultaneously degrade different classes of pesticides. Currently, we can use the approaches of synthetic biology to create a strain endowed with various catabolic pathways that do not exist in a natural microorganism. Here, we describe the metabolic engineering of a biosafety Pseudomonas putida strain KT2440 for complete mineralization of methyl parathion (MP) and gamma hexachlorocyclohexane (gamma-HCH) by functional assembly of the MP and gamma-HCH mineralization pathways. The engineered strain was genetically stable, and no growth inhibition was observed. Such a strain not only would reduce the toxicity of MP and gamma-HCH but also would prevent the accumulation of potentially toxic intermediates in the environment. Furthermore, expression of Vitreoscilla hemoglobin improved the ability of the engineered strain to sequester O2. The inoculation of the engineered strain to soils treated with MP and gamma-HCH resulted in a higher degradation rate than in noninoculated soils. Moreover, introduced GFP may be used to monitor the activity of the engineered strain during bioremediation. The engineered strain may be a promising candidate for in situ bioremediation of soil cocontaminated with MP and gamma-HCH. PMID- 26854501 TI - Attention-deficit/hyperactivity disorder across development: Predictors, resilience, and future directions. AB - The goal of this Introduction to the Special Section is to synthesize recent conceptual, methodological, and developmental advances in the field of abnormal psychology and to highlight future directions for research that will catalyze innovations in our understanding of ADHD across development. PMID- 26854502 TI - Early development of comorbidity between symptoms of attention deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). AB - Attention-deficit/hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are among the most common childhood disorders and frequently co-occur. The present study sought to advance our understanding of how comorbidity between ADHD and ODD develops during the preschool years by testing a cross-lagged model that integrates 2 prominent models: the developmental precursor model and the correlated risk factors model. Participants were 199 children (107 boys) who took part in a longitudinal study of preschoolers with behavior problems. Parent reports of ADHD and ODD symptoms were collected annually from ages 3 to 6 and a family history interview was administered at age 3. In support of the developmental precursors model, ADHD symptoms predicted later argumentative/defiant symptoms. In support of the correlated risk factors model, family histories of ADHD and ODD/CD symptoms were correlated risk factors that uniquely predicted ADHD and anger/irritable symptoms in children. Results suggest that the correlated risk factors model may best explain the development of comorbidity between symptoms of ADHD and anger/irritability, whereas the developmental precursors model may better explain the development of comorbidity between symptoms of ADHD and argumentative/defiance. PMID- 26854503 TI - Predictors of adolescent outcomes among 4-6-year-old children with attention deficit/hyperactivity disorder. AB - Children who met Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria for attention-deficit/hyperactivity disorder (ADHD) with functional impairment in at least one setting at 4-6 years of age were followed prospectively through age 18 years. On average, the 125 children (107 boys) with ADHD at baseline improved over time, but still continued to exhibit more symptoms, functional impairment, and risky behavior through adolescence than demographically matched healthy comparison children. These findings support the predictive validity of the diagnosis of ADHD at younger ages by demonstrating that the symptoms and impairment are enduring. Nonetheless, there were marked variations in developmental outcomes. Among children with ADHD, higher numbers of inattention and hyperactivity-impulsivity symptoms and higher number of concurrent symptoms (oppositional, conduct disorder, anxiety, and depression) measured at baseline each predicted higher future levels of the same dimension of symptoms. In addition, higher baseline levels of inattention, oppositional, conduct disorder, and anxiety symptoms predicted greater future functional impairment. Among children with ADHD, girls and children from families with lower family incomes had relatively poorer outcomes. Although outcomes varied along a continuum, approximately 10% of the children with ADHD at 4-6 years could be classified as functioning in the normative range on multiple measures during 15 18 years. Although this finding awaits replication, lower levels of hyperactivity impulsivity symptoms at 4-6 years predicted more normative functioning during adolescence. These findings suggest that ADHD identified in early childhood predicts an increased likelihood of functional impairment through adolescence for most, but not all, children. PMID- 26854504 TI - Attention-deficit/hyperactivity disorder developmental trajectories related to parental expressed emotion. AB - In the transition from childhood to adolescence, attention-deficit/hyperactivity disorder (ADHD) developmental trajectories diverge. Family environment, as indexed by parental expressed emotion, may moderate these trajectories. 388 children with ADHD and 127 controls were assessed using multi-informant, multimethod diagnostic procedures at up to 3 time points 1 year apart in an accelerated longitudinal design spanning ages 7-13 years. Latent-class growth analysis was used to identify developmental trajectories for parent- and teacher rated ADHD and oppositional-defiant disorder (ODD) symptoms within the ADHD sample. Parental expressed emotion, criticism, and emotional overinvolvement were coded from a 5-min speech sample at 2 time points, 1 year apart, for 208 of these children and compared among ADHD trajectory groups. RESULTS: Parent-rated hyperactivity yielded a 4-class trajectory solution in latent-class growth analysis; teacher-rated inattention yielded a 3-trajectory solution. Teacher rated ODD also yielded 3-trajectory solution. A parent-rated high persistent hyperactive group was more likely than the other ADHD groups to have parents with stable high criticism (34.6%, p < .001), with ODD symptoms controlled. A teacher identified high ODD-worsening group was more likely to experience high criticism, particularly the initial time point; (87.5%, p < .001), with hyperactivity controlled. Parental criticism, an index of the family environment, is uniquely associated with divergent developmental trajectories among children with ADHD in addition to those associated with ODD symptoms. Lay summary: For many children, ADHD symptoms decrease as they transition to adolescence. Family environmental factors, such as parental criticism, may help explain for whom symptom remission is less likely. PMID- 26854506 TI - Developmental trajectories of clinically significant attention deficit/hyperactivity disorder (ADHD) symptoms from grade 3 through 12 in a high risk sample: Predictors and outcomes. AB - Developmental trajectories of clinically significant attention deficit/hyperactivity (ADHD) symptoms were explored in a sample of 413 children identified as high risk because of elevated kindergarten conduct problems. Symptoms of inattention and hyperactivity-impulsivity were modeled simultaneously in a longitudinal latent class analyses, using parent reports collected in Grades 3, 6, 9, and 12. Three developmental trajectories emerged: (1) low levels of inattention and hyperactivity (low), (2) initially high but then declining symptoms (declining), and (3) continuously high symptoms that featured hyperactivity in childhood and early adolescence and inattention in adolescence (high). Multinomial logistic regressions examined child characteristics and family risk factors as predictors of ADHD trajectories. Relative to the low class, children in the high and declining classes displayed similar elevations of inattention and hyperactivity in early childhood. The high class was distinguished from the declining class by higher rates of aggression and hyperactivity at school and emotion dysregulation at home. In contrast, the declining class displayed more social isolation at home and school, relative to the low class. Families of children in both high and declining trajectory classes experienced elevated life stressors, and parents of children in the high class were also more inconsistent in their discipline practices relative to the low class. By late adolescence, children in the high class were significantly more antisocial than those in the low class, with higher rates of arrests, school dropout, and unemployment, whereas children in the declining class did not differ from those in the low trajectory class. The developmental and clinical implications of these findings are discussed. PMID- 26854505 TI - Temperament, executive control, and attention-deficit/hyperactivity disorder across early development. AB - Research examining factors linking early temperament and later attention-deficit/ hyperactivity disorder (ADHD) is limited by cross-sectional approaches and having the same informant rate both temperament and psychopathology. The authors used multiinformant/multimethod longitudinal data to test the hypothesis that negative emotionality during preschool is positively associated with ADHD symptom severity in middle childhood, but developing executive control mediates this relation. Children (N = 161) with and without ADHD were evaluated 3 times: parent and teacher temperament ratings and NEPSY visual attention at ages 3-4 years; Wechsler Intelligence Scale for Children-4th edition Working Memory Index and NEPSY Response Set at age 6 years; and ADHD symptoms using the Kiddie-SADS at age 7 years. Parent and teacher ratings of preschoolers' temperament were combined to form an anger/frustration composite. Similarly, an executive functioning composite was derived from age 6 measures. Bootstrapping was used to determine whether age 6 executive functioning mediated the relation between early anger/frustration and later ADHD symptom severity, while controlling for early executive functioning. Preschoolers' anger/frustration was significantly associated with later ADHD symptoms, with this relation partially mediated by age 6 executive functioning. Developing executive control mediates the relation between early anger/frustration and later ADHD symptom severity, suggesting that anger/frustration influences ADHD symptom severity through its impact on developing executive control. Early interventions targeting the harmful influences of negative emotionality or enhancing executive functioning may diminish later ADHD severity. PMID- 26854509 TI - Recent longitudinal studies of childhood attention-deficit/hyperactivity disorder: Important themes and questions for further research. AB - What we can see from the studies included here are that most cases of attention deficit/hyperactivity disorder (ADHD) persist from the preschool years into elementary school and on into adolescence, although trajectories vary considerably across individuals. Several studies here identified a small set of unique developmental trajectories for the symptoms of ADHD. All in all, the longitudinal studies of ADHD included here have greatly advanced our understanding of the developmental course and outcomes associated with childhood ADHD. PMID- 26854507 TI - Childhood conduct problems and young adult outcomes among women with childhood attention-deficit/hyperactivity disorder (ADHD). AB - We tested whether conduct problems predicted young adult functioning and psychiatric symptoms among women diagnosed with attention-deficit/hyperactivity disorder (ADHD) during childhood, in the context of 3 potential adolescent mediators: internalizing problems, peer rejection, and school failure and disciplinary problems. We controlled for childhood ADHD severity, IQ, and demographic factors, and in the mediational tests, for adolescent conduct problems. Data came from 140 participants in the Berkeley Girls With ADHD Longitudinal Study. We used bootstrapping methods to assess indirect effects (mediators). Both childhood, F(1, 118) change = 9.00, p = .003, R2 change = .069, and adolescent, F(1, 109) change = 10.41, p = .002, R2 change = .083, conduct problems were associated with worse overall functioning during young adulthood, controlling for initial ADHD severity, child IQ, and demographics. Results were similar when predicting psychiatric symptoms. Adolescent school failure and disciplinary problems mediated the relations between childhood conduct problems and both young adult functioning and externalizing problems; adolescent internalizing problems and peer conflict mediated the relation between childhood conduct problems and young adult internalizing problems. As is true for boys, childhood and adolescent conduct problems are associated with poor adult outcomes among girls with ADHD, with school failure and disciplinary problems, internalizing problems, and peer conflict functioning as mediators of these relations. PMID- 26854508 TI - Progression of impairment in adolescents with attention-deficit/hyperactivity disorder through the transition out of high school: Contributions of parent involvement and college attendance. AB - Long-term, prospective follow-up studies of children diagnosed with attention deficit/hyperactivity disorder (ADHD) show that symptoms tend to decline with age, but impairments in daily life functioning often persist into adulthood. We examined the developmental progression of impairments before and after the transition out of high school in relation to parent involvement during adolescence, parent support during adulthood, and college attendance, using 8 waves of data from the prospective 16-year follow-up of the Multimodal Treatment of ADHD (MTA) study. Participants were 548 proband children diagnosed with Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM IV; American Psychiatric Association, 2000) ADHD Combined Type and 258 age- and sex-matched comparison children (Local Normative Comparison Group; LNCG) randomly sampled from probands' schools. Impairment was assessed consistently by parent report from childhood through adulthood. Results showed that impairment worsens over time both before and after the transition to adulthood for those with ADHD histories, in contrast to non-ADHD peers, whose impairments remained stably low over time. However, impairment stabilized after leaving high school for young adults with ADHD histories who attended college. Involved parenting in adolescence was associated with less impairment overall. Attending college was associated with a stable post-high school trajectory of impairment regardless of parents' involvement during adolescence, but young adults with histories of involved parenting and who attended college were the least impaired overall. PMID- 26854511 TI - Vocal expression in schizophrenia: Less than meets the ear. AB - Abnormalities in nonverbal communication are a hallmark of schizophrenia. Results from studies using symptom rating scales suggest that these abnormalities are profound (i.e., 3-5 SDs) and occur across virtually every channel of vocal expression. Computerized acoustic analytic technologies, used to overcome practical and psychometric limitations with symptom rating scales, have found much more benign and isolated abnormalities. To better understand vocal deficits in schizophrenia and to advance acoustic analytic technologies for clinical and research applications, we examined archived speech samples from 5 separate studies, each using different speaking tasks (patient N = 309; control N = 117). We sought to: (a) use Principal Component Analysis (PCA) to identify independent vocal expression measures from a large set of variables, (b) quantify how patients with schizophrenia are abnormal with respect to these variables, (c) evaluate the impact of demographic and contextual factors (e.g., study site, speaking task), and (d) examine the relationship between clinically-rated psychiatric symptoms and vocal variables. PCA identified 7 independent markers of vocal expression. Most of these vocal variables varied considerably as a function of context and many were associated with demographic factors. After controlling for context and demographics, there were no meaningful differences in vocal expression between patients and controls. Within patients, vocal variables were associated with a range of psychiatric symptoms-though only pause length was significantly associated with clinically rated negative symptoms. The discussion centers on explaining the apparent discordance between clinical and computerized speech measures. PMID- 26854510 TI - Examining whether offspring psychopathology influences illness course in mothers with recurrent depression using a high-risk longitudinal sample. AB - Depression is known to be influenced by psychosocial stressors. For mothers with recurrent depressive illness, the presence of psychopathology in their children may have important effects on their own mental health. Although the impact of maternal depression on child mental health is well-established, no study to date, as far as we are aware, has examined the extent to which offspring psychopathology influences the course of depression in mothers with a history of recurrent depressive illness, what types of child psychopathology impact maternal mental health, or whether risks vary by child gender. Aims were to (a) Use a longitudinal design to examine whether adolescent psychopathology (depression, disruptive behavior disorder; DBD) predicts recurrence of a depressive episode and depression symptom course in women with a history of recurrent depression; and (b) To test if observed effects vary by child gender. 299 mothers with recurrent major depressive disorder and their adolescent offspring were assessed on 2 occasions, 29 months apart. Maternal depression and offspring psychopathology were assessed using semistructured interview measures. Cross generational links across time were assessed using structural equation modeling. Analyses were adjusted for past severity of maternal depression. Offspring depression symptoms but not DBD symptoms at baseline predicted future episode recurrence in mothers. Depression symptoms in daughters (beta = .16, p = .039) but not sons (beta = -.07, p = .461), predicted an increase in maternal depression symptoms across time. Psychopathology in daughters is associated with long-term depressive symptoms in women (mothers) with a history of recurrent depression. Findings highlight the importance of careful assessment and management of mental health problems in adolescents for more effective management of maternal depression. This study suggests that offspring symptoms of depression may be important for the recurrence of maternal depression episodes. Girls' symptoms of depression may be a particularly important psychosocial stressor for the development of depressive symptoms in mothers with a history of recurrent depression. PMID- 26854512 TI - Using social outcomes to inform decision-making in schizophrenia: Relationships with symptoms and functioning. AB - The outcomes of the decisions we make can be used to inform subsequent choices and behavior. We investigated whether and how people with and without schizophrenia use positive and negative social outcomes and emotional displays to inform decisions to place trust in social partners. We also investigated the impact of reversals in social partners' behavior on decisions to trust. Thirty two people with schizophrenia and 29 control participants completed a task in which they decided how much trust to place in social partners' showing either a dynamic emotional (smiling, scowling) or neutral display. Interactions were predetermined to result in positive (trust reciprocated) or negative (trust abused) outcomes, and we modeled changes in trust decisions over the course of repeated interactions. Compared to controls, people with schizophrenia were less sensitive to positive social outcomes in that they placed less trust in trustworthy social partners during initial interactions. By contrast, people with schizophrenia were more sensitive to negative social outcomes during initial interactions with untrustworthy social partners, placing less trust in these partners compared to controls. People with schizophrenia did not differ from controls in detecting social partner behavior reversals from trustworthy to untrustworthy; however, they had difficulties detecting reversals from untrustworthy to trustworthy. Importantly, decisions to trust were associated with real-world social functioning. We discuss the implications of these findings for understanding social engagement among people with schizophrenia and the development of psychosocial interventions for social functioning. PMID- 26854513 TI - Conserved SecA Signal Peptide-Binding Site Revealed by Engineered Protein Chimeras and Forster Resonance Energy Transfer. AB - Signal peptides are critical for the initiation of protein transport in bacteria by virtue of their recognition by the SecA ATPase motor protein followed by their transfer to the lateral gate region of the SecYEG protein-conducting channel complex. In this study, we have constructed and validated the use of signal peptide-attached SecA chimeras for conducting structural and functional studies on the initial step of SecA signal peptide interaction. We utilized this system to map the location and orientation of the bound alkaline phosphatase and KRRLamB signal peptides to a peptide-binding groove adjacent to the two-helix finger subdomain of SecA. These results support the existence of a single conserved SecA signal peptide-binding site that positions the signal peptide parallel to the two helix finger subdomain of SecA, and they are also consistent with the proposed role of this subdomain in the transfer of the bound signal peptide from SecA into the protein-conducting channel of SecYEG protein. In addition, our work highlights the utility of this system to conveniently engineer and study the interaction of SecA with any signal peptide of interest as well as its potential use for X-ray crystallographic studies given issues with exogenous signal peptide solubility. PMID- 26854516 TI - A Practical Solution to Stereodefined Tetrasubstituted Olefins. AB - Olefins, compounds with a carbon-carbon double bond, are of fundamental importance, and stereodefined construction of tetrasubstituted carbon-carbon double bond is a significant challenge. Here we show a unique and practical method for the preparation of stereodefined, fully substituted olefins via conjugate addition of organozinc reagents to readily available 2,3-allenals. Through mechanistic studies, it is confirmed that the geometry of the newly formed double bond is controlled by unique regiospecific oxygen-protonation of the enolate intermediates, generating 1,3-alkadienols. Such alkadienols would undergo a concerted 1,5-H-transfer reaction via a six-membered transition state to ensure the configuration of the carbon-carbon double bond in the final products. Using the readily available organozinc reagents and 2,3-allenals provides a very rapid access to a wide range of tetrasubstituted olefins with defined stereochemistry, bearing an extremely versatile aldehyde functionality. PMID- 26854514 TI - Platinum Recovery from Synthetic Extreme Environments by Halophilic Bacteria. AB - Metal recycling based on urban mining needs to be established to tackle the increasing supply risk of critical metals such as platinum. Presently, efficient strategies are missing for the recovery of platinum from diluted industrial process streams, often characterized by extremely low pHs and high salt concentrations. In this research, halophilic mixed cultures were employed for the biological recovery of platinum (Pt). Halophilic bacteria were enriched from Artemia cysts, living in salt lakes, in different salt matrices (sea salt mixture and NH4Cl; 20-210 g L(-1) salts) and at low to neutral pH (pH 3-7). The main taxonomic families present in the halophilic cultures were Halomonadaceae, Bacillaceae, and Idiomarinaceae. The halophilic cultures were able to recover >98% Pt(II) and >97% Pt(IV) at pH 2 within 3-21 h (4-453 mg Ptrecovered h(-1) g( 1) biomass). X-ray absorption spectroscopy confirmed the reduction to Pt(0) and transmission electron microscopy revealed both intra- and extracellular Pt precipitates, with median diameters of 9-30 nm and 11-13 nm, for Pt(II) and Pt(IV), respectively. Flow cytometric membrane integrity staining demonstrated the preservation of cell viability during platinum recovery. This study demonstrates the Pt recovery potential of halophilic mixed cultures in acidic saline conditions. PMID- 26854515 TI - DNA-Catalyzed Amide Hydrolysis. AB - DNA catalysts (deoxyribozymes) for a variety of reactions have been identified by in vitro selection. However, for certain reactions this identification has not been achieved. One important example is DNA-catalyzed amide hydrolysis, for which a previous selection experiment instead led to DNA-catalyzed DNA phosphodiester hydrolysis. Subsequent efforts in which the selection strategy deliberately avoided phosphodiester hydrolysis led to DNA-catalyzed ester and aromatic amide hydrolysis, but aliphatic amide hydrolysis has been elusive. In the present study, we show that including modified nucleotides that bear protein-like functional groups (any one of primary amino, carboxyl, or primary hydroxyl) enables identification of amide-hydrolyzing deoxyribozymes. In one case, the same deoxyribozyme sequence without the modifications still retains substantial catalytic activity. Overall, these findings establish the utility of introducing protein-like functional groups into deoxyribozymes for identifying new catalytic function. The results also suggest the longer-term feasibility of deoxyribozymes as artificial proteases. PMID- 26854517 TI - Multistep Electron Transfer Systems Containing [2.2]- or [3.3]Paracyclophane. AB - Paracyclophanes (PCPs), which exhibit interesting properties due to their transannular interactions, have been employed as a spacer in various electron transfer (ET) systems. In the present work, we investigated ET processes in dyads and triads containing [2.2]PCP or [3.3]PCP as donors to study their properties in multistep ET processes. The dyad molecules of PCP and 1,8-naphthalimide (NI) as a photosensitizing electron acceptor exhibited charge separation (CS) upon excitation of NI. In addition, triads of NI, PCP, and carbazole showed charge shift after an initial CS, thus confirming multistep ET. In this study, we demonstrated that use of [3.3]PCP in place of [2.2]PCP enhanced the initial CS rate. Lower oxidation potentials and a smaller reorganization energy for [3.3]PCP are shown to be key factors for this enhanced CS rate. Both of these properties are closely related to the strained structure of PCP; hence, the present results demonstrate the importance of strain in ET chemistry. PMID- 26854518 TI - Sodium-glucose cotransporter 2 inhibitors: an evidence-based practice approach to their use in the natural history of type 2 diabetes. AB - Objective The sodium-glucose cotransporter 2 (SGLT-2) inhibitors are an important addition to available treatments for patients with type 2 diabetes (T2D) as an adjunct to modifications in diet and exercise. SGLT-2 inhibitors may be prescribed alone or as add-on treatment in patients receiving metformin, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and/or insulin across the natural history of the disease. Inhibition of SGLT-2, which is responsible for approximately 90% of renal glucose reabsorption, increases urinary glucose excretion and lowers blood glucose concentrations. The objective of this review is to discuss the pathophysiology of diabetes and the contribution of the kidney to glucose homeostasis and to provide an evidence-based practice approach to clinical applications of SGLT-2 inhibitors in the treatment of T2D. Methods PubMed and Google Scholar databases were searched to identify literature published from 1990 through September 2015 examining the pathophysiology of T2D, the role of the kidney in regulating glucose concentrations, and clinical evidence for the efficacy and safety of SGLT-2 inhibitors in T2D. Results There is a need for early treatment in patients with T2D to minimize the risk of cardiovascular complications that increase morbidity and mortality. SGLT-2 inhibitors improve glycemic control, reduce body weight and blood pressure, and are associated with a low risk of hypoglycemia. Adverse events associated with SGLT-2 inhibitors include mild to moderate urinary tract and genital infections and mild dehydration potentially leading to orthostatic hypotension. Conclusions An evidence-based practice approach to examining the importance of early, proactive treatment of T2D using SGLT-2 inhibitors from initiation of pharmacotherapy to increasingly more complicated combination therapy regimens, including insulin, suggests that this treatment strategy maximizes benefits and minimizes potential side effects. The SGLT-2 inhibitors augment the arsenal of available antidiabetes agents, facilitating the ability of clinicians to design tailored treatment regimens that help patients achieve therapeutic goals. PMID- 26854519 TI - Reducing violence in forensic care - how does it resemble the domains of a recovery-oriented care? AB - BACKGROUND: Forensic psychiatry is characterized by involuntary treatment and risk of violence. The concept of recovery is rarely in focus as the primary focus is on risk assessment, violence prevention and reducing coercion in care. AIM: To determine what resources forensic staff use to avoid or prevent violent situations, and to explore how these practices resemble the domains of recovery oriented care. METHOD: Semi-structured interviews with staff who were identified by forensic patients as key workers in their recovery process. Interview texts were analyzed using interpretive content analysis. RESULTS: Staff prevent violent situations using tacit knowledge and experience, and through a shared collegial responsibility. Staff safeguard patients, encourage patient participation, and provide staff consistency. CONCLUSIONS: The results have implications for forensic care as well as psychiatry regarding the process of making recovery a reality for patients in the forensic care setting. PMID- 26854520 TI - New Cases of Thelazia callipaeda Haplotype 1 in Dogs Suggest a Wider Distribution in Romania. AB - Thelazia callipaeda is an emerging vector-borne zoonotic helminth parasitizing the conjunctival sac of a broad spectrum of definitive hosts, such as dogs, cats, rabbits, wild carnivores, and humans. Its presence is associated with mild to severe ocular disease. Here, we report two new clinical cases in dogs originating from western and southern Romania, with no travel history. On clinical examination, the nematodes were retrieved from the conjunctival sac and identified using morphological keys and molecular tools. Twenty-two adult nematodes (8 males, 14 females) were collected and were identified as T. callipaeda by morphology. The molecular analysis revealed a 100% identity with haplotype h1 of T. callipaeda. This study describes the occurrence of new autochthonous cases of thelaziosis in Romania, reinforcing the spreading trend of this zoonotic eyeworm and highlighting the need for increased awareness among medical and veterinary practitioners. Moreover, we provide additional molecular evidence for the exclusive distribution of haplotype 1 of T. callipaeda in Europe. PMID- 26854521 TI - HDL as a prognostic biomarker for coronary atherosclerosis: the role of inflammation. AB - INTRODUCTION: Emerging evidence suggests that the role of high density lipoprotein (HDL) in the atherosclerotic process is not as clear as previously thought, since atheroprotective HDL becomes atherogenic in states of increased inflammatory processes. AREAS COVERED: In this review we aim to elucidate the role of HDL as a prognostic biomarker and we discuss therapeutic approaches that aim to increase HDL and their possible clinical benefit. EXPERT OPINION: Given the structural variability and biological complexity of the HDL particle, its role in the atherosclerotic process is far from clear. According to current evidence, the atheroprotective role of HDL turns atherogenic in states of increased inflammatory processes, while even minor alterations in systemic inflammation are likely to hinder the endothelial protective effects of HDL. In accordance, significant data have revealed that HDL-related drugs may be effective in reducing cardiovascular mortality; however they are not as encouraging or unanimous as expected. Possible future goals could be to quantify either HDL subclasses or functions in an attempt to reach safer conclusions as to the prognostic importance of HDL in coronary atherosclerosis. Having achieved that, a more targeted therapy that would aim to raise either HDL functionality or to remodel HDL structure would be more easily designed. PMID- 26854522 TI - Immunoglobulin-induced hemolysis, splenomegaly and inflammation in patients with antibody deficiencies. AB - IgG replacement for primary antibody deficiencies is a safe treatment administered to prevent recurrent infections and reduce mortality. Recently, several reports described acute hemolytic episodes following IgG administration due to a passive transfer of blood group alloantibodies, including anti-A, anti B, as well as anti-Rh antibodies. Here, we reviewed and discussed the consequences of passively transferred RBCs antibodies. The chronic passive transfer of alloantibodies might also cause a subclinical condition due to a compensated extravascular chronic hemolysis with poorly understood consequences. This phenomenon might possibly represent an unrecognized cause of splenomegaly and might contribute to inflammation in patients with primary antibody deficiencies. PMID- 26854523 TI - Encouraging primary care research: evaluation of a one-year, doctoral clinical epidemiology research course. AB - OBJECTIVE: Research and PhDs are relatively rare in family medicine and primary care. To promote research, regular one-year research courses for primary care professionals with a focus on clinical epidemiology were started. This study explores the academic outcomes of the first four cohorts of research courses and surveys the participants' perspectives on the research course. DESIGN: An electronic survey was sent to the research course participants. All peer-reviewed scientific papers published by these students were retrieved by literature searches in PubMed. SETTING: Primary care in Finland. SUBJECTS: A total of 46 research course participants who had finished the research courses between 2007 and 2012. RESULTS: Of the 46 participants 29 were physicians, eight nurses, three dentists, four physiotherapists, and two nutritionists. By the end of 2014, 28 of the 46 participants (61%) had published 79 papers indexed in PubMed and seven students (15%) had completed a PhD. The participants stated that the course taught them critical thinking, and provided basic research knowledge, inspiration, and fruitful networks for research. CONCLUSION: A one-year, multi professional, clinical epidemiology based research course appeared to be successful in encouraging primary care research as measured by research publications and networking. Activating teaching methods, encouraging focus on own research planning, and support from peers and tutors helped the participants to embark on research projects that resulted in PhDs for 15% of the participants. KEY POINTS: Clinical research and PhDs are rare in primary care in Finland, which has consequences for the development of the discipline and for the availability of clinical lecturers at the universities. A clinical epidemiology oriented, one year research course increased the activity in primary care research. Focus on own research planning and learning the challenges of research with peers appeared to enhance the success of a doctoral research course. A doctoral research course encouraged networking, and the course collaboration sometimes led to paper co authoring. In the Nordic countries, the primary care health professionals are used to working in multi-professional teams. A multi-professional strategy also seems fruitful in doctoral research education. PMID- 26854524 TI - Staphylococci Related to Farm Ostriches and Their Sensitivity to Enterocins. AB - In Slovakia, ostriches are reared mainly for their meat. There is still limited information related to microflora of ostriches, including staphylococci. Knowing the composition of microflora is very important for the recognition of potential pathogenic agents. Recently, a frequent problem in animals is the occurrence of bacteria resistant to antibiotics. The aim of this study was to detect staphylococcal species in feces of farm ostriches and to test their sensitivity to antibiotics and enterocins. Altogether 140 ostriches from three age groups were sampled (n = 18, faecal mixture samples from each group) on a farm in Slovakia or on Slovak farm. From 54 fecal samples, the staphylococcal count reached an average 4. 3 +/- 0. 63 (log10) CFU/g. Twenty-four lactic acid producing strains were taxonomically classified to eight species of the genus Staphylococcus: Staphylococcus equorum, S. xylosus, S. epidermidis, S. haemolyticus, S. cohnii, S. succinus, S. warneri, and S. hominis. Strains were evaluated by secure probable species identification/probable species identification (score value up to 2.299) confirmed also by phenotypization. Most strains were sensitive to antibiotics. Four strains (S. haemolyticus SHae 111, S. haemolyticus SHAe 371, S. xylosus SX 2133, and S. warneri SW 292) were resistant to methicillin but sensitive to six or five of the seven enterocins tested (inhibitory activity 200-12,800 AU/mL). S. warneri SW 292 was sensitive to all enterocins (activity up to 12,800 AU/mL). PMID- 26854525 TI - In vitro antimicrobial susceptibility of Mycoplasma bovis clinical isolates recovered from bison (Bison bison). AB - Mycoplasma bovis is a pathogen globally affecting cattle and bison herds, causing pneumonia, arthritis, mastitis, abortions, and other symptoms, leading to huge economic losses. Many studies have been done regarding the antimicrobial susceptibility of M. bovis isolated from cattle, but no such study is available for isolates recovered from bison. For the first time, in vitro susceptibilities of 40 M. bovis clinical isolates collected from bison herds in Canada are reported here. Minimal inhibitory concentration (MIC) values were determined using Sensititre(r) plates. The most effective MIC50 and MIC90 were for spectinomycin (1 and >64 MUg/mL), tiamulin (1 and >32 MUg/mL), and tulathromycin (16 and 64 MUg/mL), whereas tetracyclines, fluoroquinolones, and florfenicol failed to inhibit growth of M. bovis bison isolates. Isolates were nonsusceptible to tetracyclines (100%), fluoroquinolones (97.5%), and tilmicosin (100%), whereas the highest susceptibility of bison clinical isolates was seen with spectinomycin (95%) and tulathromycin (67.5%). Two lung isolates (Mb283 and 348) were found resistant to both spectinomycin and tulathromycin. These results show a marked difference in antimicrobial susceptibility of bison isolates as compared with previously reported and laboratory reference cattle isolates, emphasizing the necessity of testing antimicrobial susceptibility of M. bovis bison isolates and to generate better therapeutic regime for improved recovery chances for infected bison herds across North America. PMID- 26854526 TI - A novel heterozygous splice site OPA1 mutation causes exon 10 skipping in Japanese patients with dominant optic atrophy. PMID- 26854527 TI - Novel therapies under investigation for mantle cell lymphoma. PMID- 26854528 TI - Development of a small single-ring OpenPET prototype with a novel transformable architecture. AB - The single-ring OpenPET (SROP), for which the detector arrangement has a cylinder shape cut by two parallel planes at a slant angle to form an open space, is our original proposal for in-beam PET. In this study, we developed a small prototype of an axial-shift type SROP (AS-SROP) with a novel transformable architecture for a proof-of-concept. In the AS-SROP, detectors originally forming a cylindrical PET are axially shifted little by little. We designed the small AS-SROP prototype for 4-layer depth-of-interaction detectors arranged in a ring diameter of 250 mm. The prototype had two modes: open and closed. The open mode formed the SROP with the open space of 139 mm and the closed mode formed a conventional cylindrical PET. The detectors were simultaneously moved by a rotation handle allowing them to be transformed between the two modes. We evaluated the basic performance of the developed prototype and carried out in-beam imaging tests in the HIMAC using (11)C radioactive beam irradiation. As a result, we found the open mode enabled in-beam PET imaging at a slight cost of imaging performance; the spatial resolution and sensitivity were 2.6 mm and 5.1% for the open mode and 2.1 mm and 7.3% for the closed mode. We concluded that the AS-SROP can minimize the decrease of resolution and sensitivity, for example, by transforming into the closed mode immediately after the irradiation while maintaining the open space only for the in-beam PET measurement. PMID- 26854529 TI - Eco-friendly all-carbon paper electronics fabricated by a solvent-free drawing method. AB - Here we report the fabrication of high-performance all-carbon temperature and infrared (IR) sensors with a solvent-free multiwalled carbon nanotube (MWCNT) trace as the sensing element and commercial graphite pencil trace as the electrical contact on recyclable and biodegradable cellulose filter paper without using any toxic materials or complex procedures. The temperature sensor shows a large negative temperature coefficient of resistance (TCR) in the range of -3100 ppm K(-1) to -4900 ppm K(-1), which is comparable to available commercial temperature sensors, and an activation energy of 34.85 meV. The IR sensor shows a high responsivity of 58.5 V W(-1), which is greater than reported IR sensors with similar dimensions. A detailed study of the conduction mechanism in MWCNTs with temperature and the photo response with IR illumination was done and it was found that the conduction is due to thermally assisted hopping in band tails and the photo response is bolometric in nature. The successful fabrication of these sensors on cellulose filter paper with a comparable performance to existing components indicates that it is possible to fabricate high-performance electronics using low-cost, eco-friendly materials without the need for expensive clean-room processing techniques or harmful chemicals. PMID- 26854530 TI - The problem of latent attentional capture: Easy visual search conceals capture by task-irrelevant abrupt onsets. AB - Researchers are sharply divided regarding whether irrelevant abrupt onsets capture spatial attention. Numerous studies report that they do and a roughly equal number report that they do not. This puzzle has inspired numerous attempts at reconciliation, none gaining general acceptance. The authors propose that abrupt onsets routinely capture attention, but the size of observed capture effects depends critically on how long attention dwells on distractor items which, in turn, depends critically on search difficulty. In a series of spatial cuing experiments, the authors show that irrelevant abrupt onsets produce robust capture effects when visual search is difficult, but not when search is easy. Critically, this effect occurs even when search difficulty varies randomly across trials, preventing any strategic adjustments of the attentional set that could modulate probability of capture by the onset cue. The authors argue that easy visual search provides an insensitive test for stimulus-driven capture by abrupt onsets: even though onsets truly capture attention, the effects of capture can be latent. This observation helps to explain previous failures to find capture by onsets, nearly all of which used an easy visual search. (PsycINFO Database Record PMID- 26854531 TI - Adaptive plasticity in speech perception: Effects of external information and internal predictions. AB - When listeners encounter speech under adverse listening conditions, adaptive adjustments in perception can improve comprehension over time. In some cases, these adaptive changes require the presence of external information that disambiguates the distorted speech signals, whereas in other cases mere exposure is sufficient. Both external (e.g., written feedback) and internal (e.g., prior word knowledge) sources of information can be used to generate predictions about the correct mapping of a distorted speech signal. We hypothesize that these predictions provide a basis for determining the discrepancy between the expected and actual speech signal that can be used to guide adaptive changes in perception. This study provides the first empirical investigation that manipulates external and internal factors through (a) the availability of explicit external disambiguating information via the presence or absence of postresponse orthographic information paired with a repetition of the degraded stimulus, and (b) the accuracy of internally generated predictions; an acoustic distortion is introduced either abruptly or incrementally. The results demonstrate that the impact of external information on adaptive plasticity is contingent upon whether the intelligibility of the stimuli permits accurate internally generated predictions during exposure. External information sources enhance adaptive plasticity only when input signals are severely degraded and cannot reliably access internal predictions. This is consistent with a computational framework for adaptive plasticity in which error-driven supervised learning relies on the ability to compute sensory prediction error signals from both internal and external sources of information. (PsycINFO Database Record PMID- 26854533 TI - Electrically Tunable Valley-Light Emitting Diode (vLED) Based on CVD-Grown Monolayer WS2. AB - Owing to direct band gap and strong spin-orbit coupling, monolayer transition metal dichalcogenides (TMDs) exhibit rich new physics and great applicable potentials. The remarkable valley contrast and light emission promise such two dimensional (2D) semiconductors a bright future of valleytronics and light emitting diodes (LEDs). Though the electroluminescence (EL) has been observed in mechanically exfoliated small flakes of TMDs, considering real applications, a strategy that could offer mass-product and high compatibility is greatly demanded. Large-area and high-quality samples prepared by chemical vapor deposition (CVD) are perfect candidates toward such goal. Here, we report the first demonstration of electrically tunable chiral EL from CVD-grown monolayer WS2 by constructing a p-i-n heterojunction. The chirality contrast of the overall EL reaches as high as 81% and can be effectively modulated by forward current. The success of fabricating valley LEDs based on CVD WS2 opens up many opportunities for developing large-scale production of unconventional 2D optoelectronic devices. PMID- 26854532 TI - The relationship between visual attention and visual working memory encoding: A dissociation between covert and overt orienting. AB - There is substantial debate over whether visual working memory (VWM) and visual attention constitute a single system for the selection of task-relevant perceptual information or whether they are distinct systems that can be dissociated when their representational demands diverge. In the present study, we focused on the relationship between visual attention and the encoding of objects into VWM. Participants performed a color change-detection task. During the retention interval, a secondary object, irrelevant to the memory task, was presented. Participants were instructed either to execute an overt shift of gaze to this object (Experiments 1-3) or to attend it covertly (Experiments 4 and 5). Our goal was to determine whether these overt and covert shifts of attention disrupted the information held in VWM. We hypothesized that saccades, which typically introduce a memorial demand to bridge perceptual disruption, would lead to automatic encoding of the secondary object. However, purely covert shifts of attention, which introduce no such demand, would not result in automatic memory encoding. The results supported these predictions. Saccades to the secondary object produced substantial interference with VWM performance, but covert shifts of attention to this object produced no interference with VWM performance. These results challenge prevailing theories that consider attention and VWM to reflect a common mechanism. In addition, they indicate that the relationship between attention and VWM is dependent on the memorial demands of the orienting behavior. (PsycINFO Database Record PMID- 26854534 TI - [Characterization of the Laryngeal Adductor Reflex by Stimulation with Microdroplets Impulses (Microdroplet Impulse Testing)]. AB - BACKGROUND: The larynx is considered a crossing point between breathing and swallowing pathways. During swallowing, the airway below the glottis must be protected against food components by an appropriate laryngeal closure mechanism. The laryngeal adductor reflex (LAR) with an early, probably di- or oligosynaptic interconnected ipsilateral LAR1- and a late ipsilateral and contralateral LAR2 polysynaptic component is believed to serve as such a mechanism. Here we aimed to measure and characterize the LAR in healthy volunteers and to compare the data obtained with previously published data. METHODS: We designed a prospective pilot study. 10 healthy volunteers (22-57 years) participated. To elicit the LAR we used a newly designed microdroplet impulse testing (MIT) device: very small waterdroplets were shot onto the endolaryngeal mucosa. By simultaneously observing the anatomical structures with a high speed glottography system, the time between impact of the microdroplet on the mucosa and the beginning of the adduction movement and thus an approximate value for the reflex latency could be determined. RESULTS: An early adduction movement corresponding to LAR1 could not be detected. The measured LAR2 latency time was higher than the EMG LAR2 data. No significant latency difference between right and left stimulation was found. DISCUSSION: Since we were unable to demonstrate any LAR1 component it may be that muscle activity observable by EMG may not be sufficient to lead to a visible medial vocal cord movement. The longer LAR2 latency compared to EMG data may be explained by the fact that the visually vocal cord movement occurs after a delay although muscle activity already started as evidenced by EMG.Further studies on LAR are warranted, especially since our results also raise questions about the clinical significance of the LAR. PMID- 26854535 TI - Rapid Optimization of Mcl-1 Inhibitors using Stapled Peptide Libraries Including Non-Natural Side Chains. AB - Alpha helices form a critical part of the binding interface for many protein protein interactions, and chemically stabilized synthetic helical peptides can be effective inhibitors of such helix-mediated complexes. In particular, hydrocarbon stapling of peptides to generate constrained helices can improve binding affinity and other peptide properties, but determining the best stapled peptide variant often requires laborious trial and error. Here, we describe the rapid discovery and optimization of a stapled-helix peptide that binds to Mcl-1, an antiapoptotic protein that is overexpressed in many chemoresistant cancers. To accelerate discovery, we developed a peptide library synthesis and screening scheme capable of identifying subtle affinity differences among Mcl-1-binding stapled peptides. We used our method to sample combinations of non-natural amino-acid substitutions that we introduced into Mcl-1 inhibitors in the context of a fixed helix stabilizing hydrocarbon staple that increased peptide helical content and reduced proteolysis. Peptides discovered in our screen contained surprising substitutions at sites that are conserved in natural binding partners. Library-identified peptide M3d is the most potent molecule yet tested for selectively triggering mitochondrial permeabilization in Mcl-1 dependent cell lines. Our library approach for optimizing helical peptide inhibitors can be readily applied to the study of other biomedically important targets. PMID- 26854537 TI - delta(15)N and delta(18)O Reveal the Sources of Nitrate-Nitrogen in Urban Residential Stormwater Runoff. AB - Nitrogen (N) sources are widely distributed in the complex urban environment. High-resolution data elucidating N sources in the residential catchments are not available. We used stable isotopes of N and oxygen (O) of nitrate (delta(18)O NO3(-) and delta(15)N-NO3(-)) along with delta(18)O and hydrogen (deltaD) of water (H2O) to understand the sources and transformations of N in residential stormwater runoff. Stormwater runoff samples were collected over 25 stormwater events at 5 min intervals using an autosampler installed at the residential catchment outlet pipe that drained 31 low-density homes with a total drainage area of 0.11 km(2). Bayesian mixing model results indicated that atmospheric deposition (range 43-71%) and chemical N fertilizers (range <1-49%) were the dominant NO3-N sources in the stormwater runoff and that there was a continuum of source changes during the stormwater events. Further, the NO3-N transport in the stormwater runoff from the residential catchment was driven by mixing of multiple sources and biotic (i.e., nitrification) processes. This work suggests that a better understanding of N transport and sources is needed to reduce N export and improve water quality in urban water systems. PMID- 26854536 TI - Crystal Structures of Type-II Inositol Polyphosphate 5-Phosphatase INPP5B with Synthetic Inositol Polyphosphate Surrogates Reveal New Mechanistic Insights for the Inositol 5-Phosphatase Family. AB - The inositol polyphosphate 5-phosphatase INPP5B hydrolyzes the 5-phosphate group from water- and lipid-soluble signaling messengers. Two synthetic benzene and biphenyl polyphosphates (BzP/BiPhPs), simplified surrogates of inositol phosphates and phospholipid headgroups, were identified by thermodynamic studies as potent INPP5B ligands. The X-ray structure of the complex between INPP5B and biphenyl 3,3',4,4',5,5'-hexakisphosphate [BiPh(3,3',4,4',5,5')P6, IC50 5.5 MUM] was determined at 2.89 A resolution. One inhibitor pole locates in the phospholipid headgroup binding site and the second solvent-exposed ring binds to the His-Tag of another INPP5B molecule, while a molecule of inorganic phosphate is also present in the active site. Benzene 1,2,3-trisphosphate [Bz(1,2,3)P3] [one ring of BiPh(3,3',4,4',5,5')P6] inhibits INPP5B ca. 6-fold less potently. Co crystallization with benzene 1,2,4,5-tetrakisphosphate [Bz(1,2,4,5)P4, IC50 = 6.3 MUM] yielded a structure refined at 2.9 A resolution. Conserved residues among the 5-phosphatase family mediate interactions with Bz(1,2,4,5)P4 and BiPh(3,3',4,4',5,5')P6 similar to those with the polar groups present in positions 1, 4, 5, and 6 on the inositol ring of the substrate. 5-Phosphatase specificity most likely resides in the variable zone located close to the 2- and 3-positions of the inositol ring, offering insights to inhibitor design. We propose that the inorganic phosphate present in the INPP5B-BiPh(3,3',4,4',5,5')P6 complex mimics the postcleavage substrate 5-phosphate released by INPP5B in the catalytic site, allowing elucidation of two new key features in the catalytic mechanism proposed for the family of phosphoinositide 5-phosphatases: first, the involvement of the conserved Arg-451 in the interaction with the 5-phosphate and second, identification of the water molecule that initiates 5-phosphate hydrolysis. Our model also has implications for the proposed "moving metal" mechanism. PMID- 26854538 TI - Design of a Split Intein with Exceptional Protein Splicing Activity. AB - Protein trans-splicing (PTS) by split inteins has found widespread use in chemical biology and biotechnology. Herein, we describe the use of a consensus design approach to engineer a split intein with enhanced stability and activity that make it more robust than any known PTS system. Using batch mutagenesis, we first conduct a detailed analysis of the difference in splicing rates between the Npu (fast) and Ssp (slow) split inteins of the DnaE family and find that most impactful residues lie on the second shell of the protein, directly adjacent to the active site. These residues are then used to generate an alignment of 73 naturally occurring DnaE inteins that are predicted to be fast. The consensus sequence from this alignment (Cfa) demonstrates both rapid protein splicing and unprecedented thermal and chaotropic stability. Moreover, when fused to various proteins including antibody heavy chains, the N-terminal fragment of Cfa exhibits increased expression levels relative to other N-intein fusions. The durability and efficiency of Cfa should improve current intein based technologies and may provide a platform for the development of new protein chemistry techniques. PMID- 26854540 TI - Valuable Lessons in How to Transform a Mental Health System. PMID- 26854539 TI - Targeted Gene Deletion Using DNA-Free RNA-Guided Cas9 Nuclease Accelerates Adaptation of CHO Cells to Suspension Culture. AB - Chinese hamster ovary (CHO) cells are the preferred host for the production of a wide array of biopharmaceuticals. Thus, efficient and rational CHO cell line engineering methods have been in high demand to improve quality and productivity. Here, we provide a novel genome engineering platform for increasing desirable phenotypes of CHO cells based upon the integrative protocol of high-throughput RNA sequencing and DNA-free RNA-guided Cas9 (CRISPR associated protein9) nuclease based genome editing. For commercial production of therapeutic proteins, CHO cells have been adapted for suspension culture in serum-free media, which is highly beneficial with respect to productivity and economics. To engineer CHO cells for rapid adaptation to a suspension culture, we exploited strand-specific RNA-seq to identify genes differentially expressed according to their adaptation trajectory in serum-free media. More than 180 million sequencing reads were generated and mapped to the currently available 109,152 scaffolds of the CHO-K1 genome. We identified significantly downregulated genes according to the adaptation trajectory and then verified their effects using the genome editing method. Growth-based screening and targeted amplicon sequencing revealed that the functional deletions of Igfbp4 and AqpI gene accelerate suspension adaptation of CHO-K1 cells. The availability of this strand-specific transcriptome sequencing and DNA-free RNA-guided Cas9 nuclease mediated genome editing facilitates the rational design of the CHO cell genome for efficient production of high quality therapeutic proteins. PMID- 26854541 TI - Mental Health System Transformation: Drivers for Change, Organizational Preparation, Engaging Partners and Outcomes. AB - St. Joseph's Health Care London (hereafter referred to as St. Joseph's) is a publicly funded hospital that has led mental health (MH) service system transformation in south west Ontario following directives from the Health Services Restructuring Commission (HSRC) (Sinclair 2000). This paper documents how provincial policy; HSRC directives; use of change management activities; organizational planning; and partnerships with other hospitals, community agencies and LHINs drove, shaped and accomplished the transformational change. The transformation included divestment of beds and related ambulatory services to four other hospitals, closure of beds and employment services and the construction of two state-of-the-art facilities. This paper documents the tracking of system performance measures and the outcomes that resulted. PMID- 26854542 TI - Divestment of Beds and Related Ambulatory Services to Other Communities While Maintaining a Patient- and Family-Centred Approach. AB - Individuals living with serious mental illness who require acute and/or tertiary mental healthcare services represent one of the most complex patient groups in the healthcare service delivery system. Provincial mental health policy has been committed to providing services closer to home and in the community rather than an institution wherever possible for some time. This paper articulates the strategies used by one organization to ensure the successful transfer of beds and related ambulatory services to four separate communities. In addition a case study is also provided to describe in more detail the complex changes that took place in order to accomplish the divestments of beds and related ambulatory services to one of the partner hospitals. PMID- 26854543 TI - Relentless Incrementalism: Shifting Front-Line Culture from Institutional to Recovery-Oriented Mental Healthcare. AB - St. Joseph's Health Care London is a publicly funded hospital that has led mental health service system transformation in south west Ontario following directives from the Health Services Restructuring Commission (HSRC). This paper documents how provincial policy, HSRC directives, organizational planning, research projects, quality initiatives and change management activities drove, shaped and accomplished a cultural shift at the front line to recovery-focused care. Simultaneous to these activities, beds and related ambulatory services were divested to four other hospitals, beds and employment services were closed and two new, state-of-the-art facilities were constructed, adding considerable complexities to achieving cultural change. This paper documents the incremental steps that were taken to achieve that change. PMID- 26854544 TI - Psychiatrist Health Human Resource Planning - An Essential Component of a Hospital-Based Mental Healthcare System Transformation. AB - The World Health Organization (WHO) defines health human resource planning as "the process of estimating the number of persons and the kinds of knowledge, skills, and attitudes they need to achieve predetermined health targets and ultimately health status objectives" (OHA 2015). Health human resource planning is a critical component of successful organizational and system transformation, and yet little has been written on how to do this for physicians at the local level. This paper will outline a framework for developing and managing key aspects of physician human resource planning related to both the quantity and quality of work within a hospital setting. Using the example of a complex multiphase hospital-based mental health transformation that involved both the reduction and divestment of beds and services, we will outline how we managed the physician human resource aspects to establish the number of psychiatrists needed and the desired attributes of those psychiatrists, and how we helped an existing workforce transition to meet the new expectations. The paper will describe a process for strategically aligning the selection and management of physicians to meet organizational vision and mandate. PMID- 26854545 TI - Social Determinants of Health: Housing and Income. AB - Social determinants of health such as housing and income have a large impact on mental health. Community-based initiatives have worked to address access to housing, prevent homelessness and assist people who are homeless with mental health problems. There have been several large research projects to tease out multiple subgroups such as youth and veterans and other individuals experiencing long-term homelessness. The issue of poverty has been addressed by exploring issues related to employment. The use of social enterprises is a promising practice to address issues around poverty, social inclusion and employment. Similarly, the community has worked to move hospital-based employment programs to the community. PMID- 26854546 TI - Peer Support. AB - The Mental Health Commission of Canada defines peer support as "a supportive relationship between people who have a lived experience in common ... in relation to a mental health challenge or illness ... related to their own mental health or that of a loved one" (Sunderland et al. 2013: 11). In Ontario, a key resource for peer support is the Ontario Peer Development Initiative (OPDI), which is an umbrella organization of mental health Consumer/Survivor Initiatives (CSIs) and peer support organizations across the province of Ontario. Member organizations are run by and for people with lived experience of a mental health or addiction issue and provide a wide range of services and activities within their communities. The central tenet of member organizations is the common understanding that people can and do recover with the proper supports in place and that peer support is integral to successful recovery. Nationally, Peer Support Accreditation and Certification Canada has recently been established. The relatively new national organization focuses on training and accrediting peer support workers. This paper focuses on a range of diverse peer support groups and CSIs that operate in London and surrounding areas. PMID- 26854547 TI - Prevention and Early Intervention Program for Psychoses (PEPP). AB - The Prevention and Early Intervention Program for Psychoses (PEPP) was established in 1997 for individuals with first-episode non-affective psychotic disorder. The objectives of PEPP are to improve outcomes for clients by providing a prompt, comprehensive, coordinated and effective treatment program as well as to advance research concerning early intervention for psychotic disorders. This article describes the clinical and research program and the lessons learned. PMID- 26854548 TI - Early Intervention in Mood and Anxiety Disorders: The First Episode Mood and Anxiety Program (FEMAP). AB - The First Episode Mood and Anxiety Program (FEMAP) was developed for youth with mood and/or anxiety concerns in London, Ontario, to provide early intervention for these disorders, similar to the first-episode psychosis programs across Ontario and Canada. The logic and causal models of the pathway to and through FEMAP are described and inclusion/exclusion criteria are delineated. Results of the process evaluation of the model and preliminary data from a treatment effectiveness evaluation and ongoing cost-comparison evaluation are provided. Several characteristic quotes from youth utilizing the service are included, as is an overview of utilization statistics. Challenges and lessons learned are conveyed. PMID- 26854549 TI - The South West Local Health Integration Network Behavioural Supports Ontario Experience. AB - Creating a seamless system of care with improved system and patient outcomes is imperative to the estimated 35,000 older adults living with mental health problems and addictions in the South West Local Health Integration Network. Building on existing investments and those offered through the Behavioural Supports Ontario program, strategies to improve system coordination were put in place, cross-sectoral partnerships were fostered, interdisciplinary teams from across the care continuum were linked, and educational opportunities were promoted. This evolving, co-created system has resulted in a decrease in alternate level of care cases among those with behavioural specialized needs and improved client/family perceptions of care. Also, in fiscal year 2014/15, it provided more than 7,000 care providers with learning opportunities. PMID- 26854550 TI - Mental Healthcare Delivery in London-Middlesex Ontario - The Next Frontier. AB - The next frontier for mental healthcare delivery will be focused on three facets of innovation, namely structure, process and outcome. The structure innovation will seek to develop new models of care delivery between the two hospitals and with the community. The process innovation will focus on embedding strategies to adopt a recovery and rehabilitation approach to care delivery. Lastly, the outcome innovation will use system wide quality improvement methods to drive breakthrough performance in mental healthcare. PMID- 26854552 TI - Kinetically Trapped Tetrahedral Cages via Alkyne Metathesis. AB - In dynamic covalent synthesis, kinetic traps are perceived as disadvantageous, hindering the system from reaching its thermodynamic equilibrium. Here we present the near-quantitative preparation of tetrahedral cages from simple tritopic precursors using alkyne metathesis. While the cages are the presumed thermodynamic sink, we experimentally demonstrate that the products no longer exchange their vertices once they have formed. The example reported here illustrates that kinetically trapped products may facilitate high yields of complex products from dynamic covalent synthesis. PMID- 26854551 TI - C. elegans lifespan extension by osmotic stress requires FUdR, base excision repair, FOXO, and sirtuins. AB - Moderate stress can increase lifespan by hormesis, a beneficial low-level induction of stress response pathways. 5'-fluorodeoxyuridine (FUdR) is commonly used to sterilize Caenorhabditis elegans in aging experiments. However, FUdR alters lifespan in some genotypes and induces resistance to thermal and proteotoxic stress. We report that hypertonic stress in combination with FUdR treatment or inhibition of the FUdR target thymidylate synthase, TYMS-1, extends C. elegans lifespan by up to 30%. By contrast, in the absence of FUdR, hypertonic stress decreases lifespan. Adaptation to hypertonic stress requires diminished Notch signaling and loss of Notch co-ligands leads to lifespan extension only in combination with FUdR. Either FUdR treatment or TYMS-1 loss induced resistance to acute hypertonic stress, anoxia, and thermal stress. FUdR treatment increased expression of DAF-16 FOXO and the osmolyte biosynthesis enzyme GPDH-1. FUdR induced hypertonic stress resistance was partially dependent on sirtuins and base excision repair (BER) pathways, while FUdR-induced lifespan extension under hypertonic stress conditions requires DAF-16, BER, and sirtuin function. Combined, these results demonstrate that FUdR, through inhibition of TYMS-1, activates stress response pathways in somatic tissues to confer hormetic resistance to acute and chronic stress. C. elegans lifespan studies using FUdR may need re-interpretation in light of this work. PMID- 26854553 TI - Uranium biosorption from aqueous solution onto Eichhornia crassipes. AB - Batch experiments were conducted to investigate the biosorption of U(VI) from aqueous solutions onto the nonliving biomass of an aquatic macrophyte Eichhornia crassipes. The results showed that the adsorption of U(VI) onto E. crassipes was highly pH-dependent and the best pH for U(VI) removal was 5.5. U(VI) adsorption proceeded rapidly with an equilibrium time of 30 min and conformed to pseudo second-order kinetics. The Langmuir isotherm model was determined to best describe U(VI) biosorption with a maximum monolayer adsorption capacity of 142.85 mg/g. Thermodynamic calculation results indicated that the U(VI) biosorption process was spontaneous and endothermic. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy analysis implied that the functional groups (amino, hydroxyl, and carboxyl) may be responsible for the U(VI) adsorption process, in which the coordination and ion exchange mechanisms could be involved. We conclude that E. crassipes biomass is a promising biosorbent for the removal of uranium pollutants. PMID- 26854554 TI - Characterizations of bio-accumulations, subcellular distribution and chemical forms of cesium in Brassica juncea, and Vicia faba. AB - We aim to investigate the tolerance and enrichment mechanism of cesium (Cs) in hyperaccumulation plants. In this study, Brassica juncea and Vicia faba were subjected to varying doses of Cs for 21 days to investigate the differences in bio-accumulations, subcellular distribution and chemical forms of Cs in two cultivars by differential centrifugation, and extraction of Cs in different chemical forms, respectively. The results showed that 49.87%-61.08% of the Cs were in the leaf of B. juncea, while in V. faba, 1.58%-79.29% of the Cs was in the root. The translocation factor (TF) arrived 2.79 to 3.71 in B. juncea, while it only reached 0.26 to 0.62 in V. faba. Cs subcellular distribution of the two plants was in sequence as follows: soluble fraction > cell wall >> organelles. Cs was more easily distributed to metal-sensitive fractions of V. faba. The inorganic Cs (F-ethanol), and water-soluble Cs (F-dH2O) are the main existing types of Cs in the two plants. In B. juncea, the relative content of inorganic Cs, and organic acids/CsH2PO4 (F-dH2O) were higher than that of V. faba in the stem. This suggests that Cs may induce related transporter gene expression (such as phosphate transporter, organic cation, high affinity nitrate transporter, amino acid permease, etc.) to help the transport of Cs between root to shoot. PMID- 26854555 TI - Bioreduction of U(VI) and stability of immobilized uranium under suboxic conditions. AB - In order to study the bioreduction of U(VI) and stability of immobilized uranium under suboxic conditions, microcosm were amended with ethanol, lactate and glucose, and incubated under suboxic conditions. During the incubation, total dissolved U in amended microcosms decreased from 0.95 mg/L to 0.03 mg/L. Pyrosequencing results showed that, the proportion of anaerobic microorganisms capable of reducing U(VI) under suboxic conditions was small compared with that under anoxic conditions; the proportion of aerobic and facultative anaerobic microorganisms capable of consuming the dissolved oxygen was large; and some of the facultative anaerobic microorganisms could reduce U(VI). These results indicated that different microbial communities were responsible for the bioreduction of U(VI) under suboxic and anoxic conditions. After the electron donors were exhausted, total dissolved U in the amended microcosms remained unchanged, while the U(VI)/U(IV) ratio in the solid phase of sediments increased obviously. This implied that the performance of bioreduction of the U(VI) can be maintained under suboxic condition. PMID- 26854556 TI - Atmospheric stability effects on potential radiological releases at a nuclear research facility in Romania: Characterising the atmospheric mixing state. AB - A radon-based nocturnal stability classification scheme is developed for a flat inland site near Bucharest, Romania, characterised by significant local surface roughness heterogeneity, and compared with traditional meteorologically-based techniques. Eight months of hourly meteorological and atmospheric radon observations from a 60 m tower at the IFIN-HH nuclear research facility are analysed. Heterogeneous surface roughness conditions in the 1 km radius exclusion zone around the site hinder accurate characterisation of nocturnal atmospheric mixing conditions using conventional meteorological techniques, so a radon-based scheme is trialled. When the nocturnal boundary layer is very stable, the Pasquill-Gifford "radiation" scheme overestimates the atmosphere's capacity to dilute pollutants with near-surface sources (such as tritiated water vapour) by 20% compared to the radon-based scheme. Under these conditions, near-surface wind speeds drop well below 1 m s(-1) and nocturnal mixing depths vary from ~ 25 m to less than 10 m above ground level (a.g.l.). Combining nocturnal radon with daytime ceilometer data, we were able to reconstruct the full diurnal cycle of mixing depths. Average daytime mixing depths at this flat inland site range from 1200 to 1800 m a.g.l. in summer, and 500-900 m a.g.l. in winter. Using tower observations to constrain the nocturnal radon-derived effective mixing depth, we were able to estimate the seasonal range in the Bucharest regional radon flux as: 12 mBq m(-2) s(-1) in winter to 14 mBq m(-2) s(-1) in summer. PMID- 26854558 TI - A spatiotemporal signature of cortical pain relief by tactile stimulation: An MEG study. AB - Recently, the cortical mechanisms of tactile-induced analgesia have been investigated; however, spatiotemporal characteristics have not been fully elucidated. The insular-opercular region integrates multiple sensory inputs, and nociceptive modulation by other sensory inputs occurs in this area. In this study, we focused on the insular-opercular region to characterize the spatiotemporal signature of tactile-induced analgesia using magnetoencephalography in 11 healthy subjects. Adelta (intra-epidermal electrical stimulation) inputs were modified by Abeta (mechanical tactile stimulation) selective stimulation, either independently or concurrently, to the right forearm. The optimal inter-stimulus interval (ISI) for cortical level modulation was determined after comparing the 40-, 60-, and 80-ms ISI conditions, and the calculated cortical arrival time difference between Adelta and Abeta inputs. Subsequently, we adopted a 60-ms ISI for cortical modulation and a 0-ms ISI for spinal level modulation. Source localization using minimum norm estimates demonstrated that pain-related activity was located in the posterior insula, whereas tactile-related activity was estimated in the parietal operculum. We also found significant inhibition of pain-related activity in the posterior insula due to cortical modulation. In contrast, spinal modulation was observed both in the posterior insula and parietal operculum. Subjective pain, as evaluated by the visual analog scale, also showed significant reduction in both conditions. Therefore, our results demonstrated that the multisensory integration within the posterior insula plays a key role in tactile-induced analgesia. PMID- 26854557 TI - New tissue priors for improved automated classification of subcortical brain structures on MRI. AB - Despite the constant improvement of algorithms for automated brain tissue classification, the accurate delineation of subcortical structures using magnetic resonance images (MRI) data remains challenging. The main difficulties arise from the low gray-white matter contrast of iron rich areas in T1-weighted (T1w) MRI data and from the lack of adequate priors for basal ganglia and thalamus. The most recent attempts to obtain such priors were based on cohorts with limited size that included subjects in a narrow age range, failing to account for age related gray-white matter contrast changes. Aiming to improve the anatomical plausibility of automated brain tissue classification from T1w data, we have created new tissue probability maps for subcortical gray matter regions. Supported by atlas-derived spatial information, raters manually labeled subcortical structures in a cohort of healthy subjects using magnetization transfer saturation and R2* MRI maps, which feature optimal gray-white matter contrast in these areas. After assessment of inter-rater variability, the new tissue priors were tested on T1w data within the framework of voxel-based morphometry. The automated detection of gray matter in subcortical areas with our new probability maps was more anatomically plausible compared to the one derived with currently available priors. We provide evidence that the improved delineation compensates age-related bias in the segmentation of iron rich subcortical regions. The new tissue priors, allowing robust detection of basal ganglia and thalamus, have the potential to enhance the sensitivity of voxel based morphometry in both healthy and diseased brains. PMID- 26854559 TI - Human movements and abstract motion displays activate different processes in the observer's motor system. AB - Brain imaging studies have shown that observation of both bodily movements and abstract motion displays complying with human kinematics activate the observer's motor cortex. However, it is unknown whether the same processes are active in the two conditions. Here, we addressed this issue using transcranial magnetic stimulation (TMS) to directly compare cortico-spinal excitability during observation of actions and motion stimuli that complied with or violated normal human kinematics. We found that kinematics significantly modulated the motor evoked potentials (MEPs) produced by TMS during observation of both human and abstract motion stimuli. However, only the temporal unfolding of cortico-spinal excitability during observation of human movements significantly correlated with instantaneous stimulus velocity. This correlation was present for normal movements and also for a subset of the movements having unnatural kinematics. Furthermore, bodily movements for which we found no correlation between MEPs and stimulus velocity produced significantly higher MEPs. Our novel results suggest a dissociation in how human movements and abstract motion displays engage the observer's motor system. Specifically, while both stimulus types significantly activate the observer's motor cortex, only bodily movements produce patterns of cortico-spinal excitability that closely follow the velocity profile of the observed movement. This internal "re-enactment" of observed bodily movements seems to be only partially attuned to normal human kinematics. PMID- 26854560 TI - From Pavlov to pain: How predictability affects the anticipation and processing of visceral pain in a fear conditioning paradigm. AB - Conditioned pain-related fear may contribute to hyperalgesia and central sensitization, but this has not been tested for interoceptive, visceral pain. The underlying ability to accurately predict pain is based on predictive cue properties and may alter the sensory processing and cognitive-emotional modulation of pain thus exacerbating the subjective pain experience. In this functional magnetic resonance imaging study using painful rectal distensions as unconditioned stimuli (US), we addressed changes in the neural processing of pain during the acquisition of pain-related fear and subsequently tested if conditioned stimuli (CS) contribute to hyperalgesia and increased neural responses in pain-encoding regions. N=49 healthy volunteers were assigned to one of two groups and underwent 3T fMRI during acquisition of either differential fear conditioning (predictable) or non-contingent presentation of CS and US (unpredictable). During a subsequent test phase, pain stimuli signaled randomly by the CSs were delivered. For the acquisition, results confirmed differential conditioning in the predictable but not the unpredictable group. With regard to activation in response to painful stimuli, the unpredictable compared to the predictable group revealed greater activation in pain-encoding (somatosensory cortex, insula) and pain-modulatory (prefrontal and cingulate cortices, periaqueductal grey, parahippocampus) regions. In the test phase, no evidence of hyperalgesia or central sensitization was found, but the predictable group demonstrated enhanced caudate nucleus activation in response to CS(-)-signaled pain. These findings support that during fear conditioning, the ability to predict pain affects neural processing of visceral pain and alters the associative learning processes underlying the acquisition of predictive properties of cues signaling pain, but conditioned pain-related fear does not result in visceral hyperalgesia or central sensitization. PMID- 26854561 TI - Primary motor cortex changes after amputation correlate with phantom limb pain and the ability to move the phantom limb. AB - A substantial body of evidence documents massive reorganization of primary sensory and motor cortices following hand amputation, the extent of which is correlated with phantom limb pain. Many therapies for phantom limb pain are based upon the idea that plastic changes after amputation are maladaptive and attempt to normalize representations of cortical areas adjacent to the hand area. Recent data suggest, however, that higher levels of phantom pain are associated with stronger local activity and more structural integrity in the missing hand area rather than with reorganization of neighbouring body parts. While these models appear to be mutually exclusive they could co-exist, and one reason for the apparent discrepancy between them might be that no single study has examined the organisation of lip, elbow, and hand movements in the same participants. In this study we thoroughly examined the 3D anatomy of the central sulcus and BOLD responses during movements of the hand, elbow, and lips using MRI techniques in 11 upper-limb amputees and 17 healthy control subjects. We observed different reorganizational patterns for all three body parts as the former hand area showed few signs of reorganization, but the lip and elbow representations reorganized and shifted towards the hand area. We also found that poorer voluntary control and higher levels of pain in the phantom limb were powerful drivers of the lip and elbow topological changes. In addition to providing further support for the maladaptative plasticity model, we demonstrate for the first time that motor capacities of the phantom limb correlate with post-amputation reorganization, and that this reorganization is not limited to the face and hand representations but also includes the proximal upper-limb. PMID- 26854562 TI - Water Drop Evaporation on Mushroom-like Superhydrophobic Surfaces: Temperature Effects. AB - We report on experiments of drop evaporation on heated superhydrophobic surfaces decorated with micrometer-sized mushroom-like pillars. We analyze the influence of two parameters on the evaporation dynamics: the solid-liquid fraction and the substrate temperature, ranging between 30 and 80 degrees C. In the different configurations investigated, the drop evaporation appears to be controlled by the contact line dynamics (pinned or moving). The experimental results show that (i) in the pinned regime, the depinning angles increase with decreasing contact fraction and the substrate heating promotes the contact line depinning and (ii) in the moving regime, the droplet motion is described by periodic stick-slip events and contact-angle oscillations. These features are highly smoothed at the highest temperatures, with two possible mechanisms suggested to explain such a behavior, a reduction in the elasticity of the triple line and a decrease in the depinning energy barriers. For all surfaces, the observed remarkable stability of the "fakir" state to the temperature is attributed to the re-entrant micropillar curvature that prevents surface imbibition. PMID- 26854563 TI - Speciation of Nitrogen-Bearing Species Using Negative and Positive Secondary Ion Spectra with Nano Secondary Ion Mass Spectrometry. AB - In this study, we demonstrate that Nano Secondary Ion Mass Spectrometry (NanoSIMS) can be used to differentiate different nitrogen-containing species commonly observed in atmospheric aerosol particles with micrometer or submicrometer spatial resolution, on the basis of the relative intensity of secondary ion signals, both in negative and positive secondary ion mode, without the need to chemically or physically separate the samples. Compounds tested include nitrate, nitrite, ammonium salts, urea, amino acids, sugars, organic acids, amides, triazine, imidazole, protein, and biological tissue. We show that NO2(-) secondary ions are unique to the decomposition of nitrate and nitrite salts, whereas NH4(+) secondary ions are unique to samples containing ammonium ions, with low signal intensities observed from amino groups but none from biological tissue. CN(-) signals are obtained from all nitrogen-bearing compounds, but relative signal intensities are the highest for organic nitrogen containing compounds. We demonstrate that quantitative determination of the elemental fractions of carbon, oxygen, and nitrate in nanometer-sized aerosol samples using normalized secondary ion intensities is possible. We further demonstrate that stable isotope ratios measured on in-house standards of unknown isotopic composition using the (12)C(15)N(-)/(12)C(14)N(-) ratio (all nitrogen containing species), the (15)N(16)O2(-)/(14)N(16)O2(-) ratio (nitrate and nitrite species), and the (15)NH4(+)/(14)NH4(+) ratio (ammonium salts, amino acids, and urea) are stable and sufficiently precise for nitrogen isotope analysis. PMID- 26854564 TI - Unparalleled Ease of Access to a Library of Biheteroaryl Fluorophores via Oxidative Cross-Coupling Reactions: Discovery of Photostable NIR Probe for Mitochondria. AB - The development of straightforward accesses to organic functional materials through C-H activation is a revolutionary trend in organic synthesis. In this article, we propose a concise strategy to construct a large library of donor acceptor-type biheteroaryl fluorophores via the palladium-catalyzed oxidative C H/C-H cross-coupling of electron-deficient 2H-indazoles with electron-rich heteroarenes. The directly coupled biheteroaryl fluorophores, named Indazo Fluors, exhibit continuously tunable full-color emissions with quantum yields up to 93% and large Stokes shifts up to 8705 cm(-1) in CH2Cl2. By further fine tuning of the substituent on the core skeleton, Indazo-Fluor 3l (FW = 274; lambdaem = 725 nm) is obtained as the lowest molecular weight near-infrared (NIR) fluorophore with emission wavelength over 720 nm in the solid state. The NIR dye 5h specifically lights up mitochondria in living cells with bright red luminescence. Typically, commercially available mitochondria trackers suffer from poor photostability. Indazo-Fluor 5h exhibits superior photostability and very low cytotoxicity, which would be a prominent reagent for in vivo mitochondria imaging. PMID- 26854565 TI - Secreted IGFBP5 mediates mTORC1-dependent feedback inhibition of IGF-1 signalling. AB - The PI(3)K-Akt-mTORC1 pathway is a highly dynamic network that is balanced and stabilized by a number of feedback inhibition loops. Specifically, activation of mTORC1 has been shown to lead to the inhibition of its upstream growth factor signalling. Activation of the growth factor receptors is triggered by the binding of their cognate ligands in the extracellular space. However, whether secreted proteins contribute to the mTORC1-dependent feedback loops remains unclear. We found that cells with hyperactive mTORC1 secrete a protein that potently inhibits the function of IGF-1. Using a large-scale, unbiased quantitative proteomic platform, we comprehensively characterized the rapamycin-sensitive secretome in TSC2(-/-) mouse embryonic fibroblasts, and identified IGFBP5 as a secreted, mTORC1 downstream effector protein. IGFBP5 is a direct transcriptional target of HIF1, which itself is a known mTORC1 target. IGFBP5 is a potent inhibitor of both the signalling and functional outputs of IGF-1. Once secreted, IGFBP5 cooperates with intracellular branches of the feedback mechanisms to block the activation of IGF-1 signalling. Finally, IGFBP5 is a potential tumour suppressor, and the proliferation of IGFBP5-mutated cancer cells is selectively blocked by IGF-1R inhibitors. PMID- 26854566 TI - Femtosecond control of electric currents in metallic ferromagnetic heterostructures. AB - The idea to use not only the charge but also the spin of electrons in the operation of electronic devices has led to the development of spintronics, causing a revolution in how information is stored and processed. A novel advancement would be to develop ultrafast spintronics using femtosecond laser pulses. Employing terahertz (10(12) Hz) emission spectroscopy and exploiting the spin-orbit interaction, we demonstrate the optical generation of electric photocurrents in metallic ferromagnetic heterostructures at the femtosecond timescale. The direction of the photocurrent is controlled by the helicity of the circularly polarized light. These results open up new opportunities for realizing spintronics in the unprecedented terahertz regime and provide new insights in all optical control of magnetism. PMID- 26854568 TI - Imaging: Nano meets femto. PMID- 26854567 TI - Plasmonic nanofocused four-wave mixing for femtosecond near-field imaging. AB - Femtosecond nonlinear optical imaging with nanoscale spatial resolution would provide access to coupled degrees of freedom and ultrafast response functions on the characteristic length scales of electronic and vibrational excitations. Although near-field microscopy provides the desired spatial resolution, the design of a broadband high-contrast nanoprobe for ultrafast temporal resolution is challenging due to the inherently weak nonlinear optical signals generated in subwavelength volumes. Here, we demonstrate broadband four-wave mixing with enhanced nonlinear frequency conversion efficiency at the apex of a nanometre conical tip. Far-field light is coupled through a grating at the shaft of the tip, generating plasmons that propagate to the apex while undergoing asymptotic compression and amplification, resulting in a nonlinear conversion efficiency of up to 1 * 10(-5). We apply this nonlinear nanoprobe to image the few-femtosecond coherent dynamics of plasmonic hotspots on a nanostructured gold surface with spatial resolution of a few tens of nanometres. The approach can be generalized towards spatiotemporal imaging and control of coherent dynamics on the nanoscale, including the extension to multidimensional spectroscopy and imaging. PMID- 26854569 TI - A quantum phase switch between a single solid-state spin and a photon. AB - Interactions between single spins and photons are essential for quantum networks and distributed quantum computation. Achieving spin-photon interactions in a solid-state device could enable compact chip-integrated quantum circuits operating at gigahertz bandwidths. Many theoretical works have suggested using spins embedded in nanophotonic structures to attain this high-speed interface. These proposals implement a quantum switch where the spin flips the state of the photon and a photon flips the spin state. However, such a switch has not yet been realized using a solid-state spin system. Here, we report an experimental realization of a spin-photon quantum switch using a single solid-state spin embedded in a nanophotonic cavity. We show that the spin state strongly modulates the polarization of a reflected photon, and a single reflected photon coherently rotates the spin state. These strong spin-photon interactions open up a promising direction for solid-state implementations of high-speed quantum networks and on chip quantum information processors using nanophotonic devices. PMID- 26854570 TI - A deep etching mechanism for trench-bridging silicon nanowires. AB - Introducing a single silicon nanowire with a known orientation and dimensions to a specific layout location constitutes a major challenge. The challenge becomes even more formidable, if one chooses to realize the task in a monolithic fashion with an extreme topography, a characteristic of microsystems. The need for such a monolithic integration is fueled by the recent surge in the use of silicon nanowires as functional building blocks in various electromechanical and optoelectronic applications. This challenge is addressed in this work by introducing a top-down, silicon-on-insulator technology. The technology provides a pathway for obtaining well-controlled silicon nanowires along with the surrounding microscale features up to a three-order-of-magnitude scale difference. A two-step etching process is developed, where the first shallow etch defines a nanoscale protrusion on the wafer surface. After applying a conformal protection on the protrusion, a deep etch step is carried out forming the surrounding microscale features. A minimum nanowire cross-section of 35 nm by 168 nm is demonstrated in the presence of an etch depth of 10 MUm. Nanowire cross sectional features are characterized via transmission electron microscopy and linked to specific process steps. The technology allows control on all dimensional aspects along with the exact location and orientation of the silicon nanowire. The adoption of the technology in the fabrication of micro and nanosystems can potentially lead to a significant reduction in process complexity by facilitating direct access to the nanowire during surface processes such as contact formation and doping. PMID- 26854571 TI - Correction: Genomic Comparison of Non-Typhoidal Salmonella enterica Serovars Typhimurium, Enteritidis, Heidelberg, Hadar and Kentucky Isolates from Broiler Chickens. PMID- 26854572 TI - Modelling the temperature evolution of bone under high intensity focused ultrasound. AB - Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has been clinically shown to be effective for palliative pain management in patients suffering from skeletal metastasis. The underlying mechanism is supposed to be periosteal denervation caused by ablative temperatures reached through ultrasound heating of the cortex. The challenge is exact temperature control during sonication as MR-based thermometry approaches for bone tissue are currently not available. Thus, in contrast to the MR-HIFU ablation of soft tissue, a thermometry feedback to the HIFU is lacking, and the treatment of bone metastasis is entirely based on temperature information acquired in the soft tissue adjacent to the bone surface. However, heating of the adjacent tissue depends on the exact sonication protocol and requires extensive modelling to estimate the actual temperature of the cortex. Here we develop a computational model to calculate the spatial temperature evolution in bone and the adjacent tissue during sonication. First, a ray-tracing technique is used to compute the heat production in each spatial point serving as a source term for the second part, where the actual temperature is calculated as a function of space and time by solving the Pennes bio-heat equation. Importantly, our model includes shear waves that arise at the bone interface as well as all geometrical considerations of transducer and bone geometry. The model was compared with a theoretical approach based on the far field approximation and an MR-HIFU experiment using a bone phantom. Furthermore, we investigated the contribution of shear waves to the heat production and resulting temperatures in bone. The temperature evolution predicted by our model was in accordance with the far field approximation and agreed well with the experimental data obtained in phantoms. Our model allows the simulation of the HIFU treatments of bone metastasis in patients and can be extended to a planning tool prior to MR-HIFU treatments. PMID- 26854573 TI - Inhibition of Na(+)-K(+)-2Cl(-) Cotransporter-1 attenuates traumatic brain injury induced neuronal apoptosis via regulation of Erk signaling. AB - Traumatic brain injury (TBI) is the leading cause of mortality and morbidity worldwide and is characterized by immediate brain damage and secondary injuries, such as brain edema and ischemia. However, the exact pathological mechanisms that comprise these associated secondary injuries have not been fully elucidated. This study aimed to investigate the role of the Na(+)-K(+)-2Cl(-) cotransporter-1 (NKCC1) in the disruption of ion homeostasis and neuronal apoptosis in TBI. Using a traumatic neuron injury (TNI) model in vitro and a controlled cortex injury (CCI) model in vivo, the present study investigated changes in the expression and effects of NKCC1 in TBI using western blot, RNA interference, a lactate dehydrogenase (LDH) release assay, TdT-mediated dUTP Nick end-labeling (TUNEL) analysis, sodium imaging, brain water content, and neurological severity scoring. TBI induced the expression of NKCC1 to be significantly upregulated in the cortex, both in vitro and in vivo. Pharmacological inhibitor bumetanide (Bume) or NKCC1 RNA interference significantly attenuated TBI-induced intracellular Na(+) increase, inhibited neuronal apoptosis, and improved brain edema and neurological function. Furthermore, NKCC1 inhibition also significantly inhibited TBI-induced extracellular signal-regulated kinase (Erk) activation. Erk inhibition significantly protected neurons from TBI injury; however, Erk inhibition had no effect on NKCC1 expression or the neuroprotective effect of NKCC1 inhibition against TBI. This study demonstrates the role of NKCC1 in TBI-induced brain cortex injury, establishing that NKCC1 may play a neurotoxic role in TBI and that the inhibition of NKCC1 may protect neurons from TBI via the regulation of Erk signaling. PMID- 26854574 TI - Low-Temperature Selective Catalytic Reduction of NO with NH3 over Mn2O3-Doped Fe2O3 Hexagonal Microsheets. AB - Mn2O3-doped Fe2O3 hexagonal microsheets were prepared for the low-temperature selective catalytic reduction (SCR) of NO with NH3. These hexagonal microsheets were characterized by SEM, TEM, XRD, BET, XPS, NH3-TPD, H2-TPR, and in situ DRIFT and were shown to exhibit a considerable uniform hexagonal microsheet structure and excellent low temperature SCR efficiency. When doped with different Mn molar ratios, Mn2O3 was detected in the Fe2O3 hexagonal microsheets based on the XRD results without the presence of other MnOX species. In addition, the hexagonal microsheets with a Mn/Fe molar ratio of 0.2 showed the best SCR removal performance among the materials, where a 98% NO conversion ratio at 200 degrees C at a space velocity of 30,000 h(-1) was obtained. Meanwhile, excellent tolerances to H2O and SO2, as well as high thermal stability, were obtained in Mn2O3-doped Fe2O3 hexagonal microsheets. Moreover, on the basis of the XPS and in situ DRIFT results, it can be suggested that coupled Mn2O3 nanocrystals played a key role at low temperatures and produced a possible redox reaction mechanism in the SCR process. PMID- 26854575 TI - The enhancement of immune function and activation of NF-kappaB by resveratrol treatment in immunosuppressive mice. AB - Resveratrol, a kind of natural product found in over 70 plants, possesses both immunomodulatory and anticancer effects. Many reports have shown that resveratrol has the bidirectional regulation effects on antigen presenting and cellular immunity. However, few reports have evaluated the effects of resveratrol on reinforcing immunity recovery via activating nuclear factor -kappaappa B (NF kappaB). In the present study, we investigated the effects of resveratrol on recovery and reconstruction of immune function by detecting nonspecific and specific immunity in immunosuppressive mice. We found that, compared to the immunosuppressive mice, the spleen index and spleen lymphocyte proliferation of resveratrol-treated mice (30 mg/kg body weight) were enhanced. After resveratrol treatment (15 mg/kg body weight), the function of peritoneal macrophages was enhanced and the CD4+ cells were increased in peripheral blood. The expressions of serum cytokines related to immune function, including interleukin (IL) 1alpha/beta, IL-2, tumor necrosis factor-alpha and NF-kappaB were up-regulated in a dose-dependent manner. The expression of the transcription factor NF-kappaB in spleen was enhanced after resveratrol-treatment. The immuno-enhancement effects of resveratrol were similar to that of levamisole (served as positive control). These results demonstrated that resveratrol had potent immune enhancement activity in immunosuppressive mice, and one possible mechanism of action was to activate the NF-kappaB. PMID- 26854576 TI - The effect of local anesthetic on pro-inflammatory macrophage modulation by mesenchymal stromal cells. AB - Administering local anesthetics (LAs) peri- and post-operatively aims to prevent or mitigate pain in surgical procedures and after tissue injury in cases of osteoarthritis (OA) and other degenerative diseases. Innovative tissue protective and reparative therapeutic interventions such as mesenchymal stromal cells (MSCs) are likely to be exposed to co-administered drugs such as LAs. Therefore, it is important to determine how this exposure affects the therapeutic functions of MSCs and other cells in their target microenvironment. In these studies, we measured the effect of LAs, lidocaine and bupivacaine, on macrophage viability and pro-inflammatory secretion. We also examined their effect on modulation of the macrophage pro-inflammatory phenotype in an in vitro co-culture system with MSCs, by quantifying macrophage tumor necrosis factor (TNF)-alpha secretion and MSC prostaglandin E2 (PGE2) production. Our studies indicate that both LAs directly attenuated macrophage TNF-alpha secretion, without significantly affecting viability, in a concentration- and potency-dependent manner. LA mediated attenuation of macrophage TNF-alpha was sustained in co-culture with MSCs, but MSCs did not further enhance this anti-inflammatory effect. Concentration- and potency-dependent reductions in macrophage TNF-alpha were concurrent with decreased PGE2 levels in the co-cultures further indicating MSC independent macrophage attenuation. MSC functional recovery from LA exposure was assessed by pre-treating MSCs with LAs prior to co-culture with macrophages. Both MSC attenuation of TNF-alpha and PGE2 secretion were impaired by pre-exposure to the more potent bupivacaine and high dose of lidocaine in a concentration dependent manner. Therefore, LAs can affect anti-inflammatory function by both directly attenuating macrophage inflammation and MSC secretion and possibly by altering the local microenvironment which can secondarily reduce MSC function. Furthermore, the LA effect on MSC function may persist even after LA removal. PMID- 26854578 TI - The efficacy of pregabalin in patients with moderate and severe pain due to diabetic peripheral neuropathy. AB - Objective To compare the therapeutic response to pregabalin in patients with moderate or severe painful diabetic peripheral neuropathy (pDPN). Research design and methods Data were pooled from 11 placebo-controlled trials to evaluate the efficacy of pregabalin flexible or fixed dose (150, 300 or 600 mg/day) in pDPN patients with mean baseline pain scores of >=4 to <7 (moderate) or >=7 to <=10 (severe). Last observation carried forward imputation was used. Study number/ClinicalTrials.gov identifier 1008-014/-, 1008-029/-, 1008-040/-, 1008 131/-, 1008-149/-, 1008-000-155/-, A0081030/NCT00156078, A0081060/NCT00159679, A0081071/NCT00143156, A0081081/NCT00301223, A0081163/NCT00553475. Main outcome measures Pregabalin-mediated change in pain, pain-related sleep interference (PRSI) and patient global impression of change (PGIC) were compared versus placebo and between moderate and severe pain cohorts. Adverse events (AEs) were reported. Results At baseline, 1816 patients had moderate pain (pregabalin, n = 1189) and 1119 patients had severe pain (pregabalin, n = 720). Pregabalin significantly reduced pain scores at endpoint compared with placebo when patients of all pain levels were combined (all doses; p < 0.05). In the moderate and severe pain cohorts, pregabalin treatment (300, 600 mg/day or flexible) significantly reduced mean pain scores at endpoint compared with placebo (p < 0.01). Pain reduction was greatest in patients with severe baseline pain compared with moderate baseline pain (pregabalin 300, 600 mg/day or flexible; p < 0.0001). Pregabalin improved PRSI and PGIC in the moderate and severe cohorts compared with placebo. The greatest improvement in PRSI also occurred in the severe cohort. Treatment-emergent AEs, most commonly dizziness, somnolence and peripheral edema, occurred more frequently in patients treated with pregabalin compared with placebo. Conclusions Pregabalin was effective in pDPN patients with both moderate and severe baseline pain. Patients with severe pain exhibited greater improvements in pain and PRSI than patients with moderate pain. Pain severity may, in part, predict therapeutic response to pregabalin. PMID- 26854579 TI - Erratum. PMID- 26854577 TI - Loxoprofen sodium induces the production of complement C5a in human serum. AB - Basophil activation test (BAT) is an in vitro allergy test that is useful to identify allergens that cause IgE-dependent allergies. The test has been used to detect not only food allergies and allergies caused by environmental factors but also to detect drug hypersensitivity, which has been known to include IgE independent reactions. In our preliminary studies in which BAT was applied to detect hypersensitivity of loxoprofen, a non-steroidal anti-inflammatory drug (NSAID), conventional BAT with incubation for 30min did not show basophil activation by means of increased CD203c expression. In this study, we extended the incubation time to 24h on the basis of the hypothesis that loxoprofen indirectly activates basophils. Basophils from healthy control donors as well as allergic patients showed up-regulation of CD203c after incubation with loxoprofen for 24h. Activation was induced using loxoprofen-treated serum. Proteomic and pharmacologic analyses revealed that serum incubation with loxoprofen generated an active complement component C5a, which induced CD203c expression via binding to the C5a receptor on basophils. Because C3a production was also detected after incubation for 24h, loxoprofen is likely to stimulate the complement classical pathway. Our findings suggest that the complement activation is involved in drug hypersensitivity and the suppression of this activation may contribute to the elimination of false positive of BAT for drug allergies. PMID- 26854580 TI - Closed membrane shapes with attached BAR domains subject to external force of actin filaments. AB - Membrane deformations induced by attached BAR superfamily domains could trigger or facilitate the growth of plasma membrane protrusions. The BAR domain family consists of BAR, F-BAR and I-BAR domains, each enforcing a different local curvature when attached to the membrane surface. Our theoretical study mainly focuses on the role of I-BAR in the membrane tubular deformations generated or stabilised by actin filaments. The influence of the area density of membrane attached BAR domains and their intrinsic curvature on the closed membrane shapes (vesicles) was investigated numerically. We derived an analytical approximative expression for the critical relative area density of BARs at which the membrane tubular protrusions on vesicles are most prominent. We have shown that the BARs with a higher intrinsic curvature induce thinner and longer cylindrical protrusions. The average orientation of the membrane attached BARs is altered when the vesicle shape is subjected to external force of growing actin rod-like structure inside a vesicle. The average orientation angle of membrane attached BARs may indicate whether the actin filaments are just stabilising the protrusion or generating it by stretching the vesicle. PMID- 26854581 TI - The role of hyaluronic acid inclusion on the energetics of encapsulation and release of a protein molecule from chitosan-based nanoparticles. AB - The synergistic effects of the polysaccharides chitosan (CS) and hyaluronic acid (HA) formulated into hybrid nanoparticles are promising for drug delivery. In the present work, we performed a detailed analysis of the molecular interactions involved in the TPP-assisted ionotropic gelation of CS hybrid nanoparticles with the objective of investigating the impact of HA inclusion on the particle formulation and on the in vitro release of insulin (INS) as a protein cargo. To do that, an in-depth thermodynamic study was carried out by isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC) techniques. Such analysis allowed us to elucidate the type and extent of interactions established by INS within the hybrid nanoparticles and to get further knowledge on the nature of its release mechanism in vitro. Overall, INS release from the CS nanoparticles was thermodynamically driven, and when including HA a weaker INS binding to the nanoparticles, hence, a faster release rate in vitro were observed. As a negative polyelectrolyte, HA might have sterically blocked the activated sites of CS, such as the amino groups, through chain entanglement, thereby, attenuating the competitive binding interactions of INS. As a consequence, INS might have experienced a spatial exclusion onto the surface of the hybrid nanoparticles to a greater extent which, in turn, would explain its initial abrupt release. PMID- 26854582 TI - Real-time measurements to characterize dynamics of emulsion interface during simulated intestinal digestion. AB - Efficient delivery of bioactives remains a critical challenge due to their limited bioavailability and solubility. While many encapsulation systems are designed to modulate the digestion and release of bioactives within the human gastrointestinal tract, there is limited understanding of how engineered structures influence the delivery of bioactives. The objective of this study was to develop a real-time quantitative method to measure structural changes in emulsion interface during simulated intestinal digestion and to correlate these changes with the release of free fatty acids (FFAs). Fluorescence resonant energy transfer (FRET) was used for rapid in-situ measurement of the structural changes in emulsion interface during simulated intestinal digestion. By using FRET, changes in the intermolecular spacing between the two different fluorescent probes labeled emulsifier were characterized. Changes in FRET measurements were compared with the release of FFAs. The results showed that bile salts and pancreatic lipase interacted immediately with the emulsion droplets and disrupted the emulsion interface as evidenced by reduction in FRET efficacy compared to the control. Similarly, a significant amount of FFAs was released during digestion. Moreover, addition of a second layer of polymers at emulsion interface decreased the extent of interface disruption by bile salts and pancreatic lipase and impacted the amount or rate of FFA release during digestion. These results were consistent with the lower donor/acceptor ratio of the labeled probes from the FRET result. Overall, this study provides a novel approach to analyze the dynamics of emulsion interface during digestion and their relationship with the release of FFAs. PMID- 26854583 TI - Carbon dots incorporated polymeric hydrogels as multifunctional platform for imaging and induction of apoptosis in lung cancer cells. AB - Multifunctional hydrogels offer a seemingly efficient system for delivery of drugs and bioimaging modalities. The present study deals with the facile development of chitosan-based hydrogel formulation composed of highly fluorescent carbon dots (CDs) and loaded with a model anticancer drug, 5-Fluorouracil (5-FU). Herein, CDs were embedded firmly within the hydrogel matrices (CD-HY) via non covalent interactions during the ionic cross-linking reaction. Furthermore, these hydrogels could effectively encapsulate 5-FU through hydrophobic interactions to form 5-FU@CD-HY. In this way, it was possible to combine the merits of both CDs and 5-FU on a common platform for monitoring the cellular uptake as well as therapeutic effects. Field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) illustrated the porous nature and formation of 5-FU@CD-HY. Besides, functional characteristics of 5-FU@CD-HY such as surface area, mechanical strength, swelling behavior and drug release were investigated. In vitro studies revealed the multifunctional aspects of 5-FU@CD-HY in monitoring the cellular uptake and inflicting apoptosis in A549 cells. Green fluorescence of CDs in 5-FU@CD-HY aided the qualitative and quantitative assessment of cellular uptake. In addition to this, the fluorescence of CDs could be used to detect apoptosis instigated by 5-FU, eliminating the need for multiplex dyes. Induction of apoptosis in 5-FU@CD-HY treated cells was evidenced by changes in cell cycle distributions and visualization of characteristic apoptotic bodies through FE-SEM. Apoptotic gene expression studies further elucidate the molecular mechanism involved in eliciting apoptosis. Thus, hydrogels mediated integration of fluorescent CDs with chemotherapeutic agents provides a new dimension for the potential use of hydrogels in cancer theranostics. PMID- 26854584 TI - Time and direction preparation of the long latency stretch reflex. AB - This study investigated time and direction preparation of motor response to force load while intending to maintain the finger at the initial neutral position. Force load extending or flexing the index finger was given while healthy humans intended to maintain the index finger at the initial neutral position. Electromyographic activity was recorded from the first dorsal interosseous muscle. A precue with or without advanced information regarding the direction of the forthcoming force load was given 1000ms before force load. Trials without the precue were inserted between the precued trials. A long latency stretch reflex was elicited by force load regardless of its direction, indicating that the long latency stretch reflex is elicited not only by muscle stretch afferents, but also by direction-insensitive sensations. Time preparation of motor response to either direction of force load enhanced the long latency stretch reflex, indicating that time preparation is not mediated by afferent discharge of muscle stretch. Direction preparation enhanced the long latency stretch reflex and increased corticospinal excitability 0-20ms after force load when force load was given in the direction stretching the muscle. These enhancements must be induced by preset of the afferent pathway mediating segmental stretch reflex. PMID- 26854585 TI - Theoretical Demonstration of the Ionic Barristor. AB - In this Letter, we use first-principles simulations to demonstrate the absence of Fermi-level pinning when graphene is in contact with transition metal dichalcogenides (TMDs). We find that formation of either an ohmic or Schottky contact is possible. Then we show that, due to the shallow density of states around its Fermi level, the work function of graphene can be tuned by ion adsorption. Finally we combine work function tuning of graphene and an ideal contact between graphene and TMDs to propose an ionic barristor design that can tune the work function of graphene with a much wider margin than current barristor designs, achieving a dynamic switching among p-type ohmic contact, Schottky contact, and n-type ohmic contact in one device. PMID- 26854586 TI - Pediatric Headache and Epilepsy Comorbidity in the Pragmatic Clinical Setting. AB - INTRODUCTION: Demographic and clinical data were collected from three cross sectional samples, from the headache and epilepsy clinics according to respective protocols. During structured interviews, we examined the co-occurrence of headaches and epilepsy in children and their families: (1) 172 children from the headache clinic, were questioned for the number and type of epileptic seizures and epilepsy diagnosis. (2) Around 70 children from the epilepsy clinic for the frequency and type of headaches and headache syndrome diagnosis. (3) A total of 149 parents of children with benign childhood epilepsy with centro-temporal spikes (BCECTS) and childhood absence epilepsy (CAE), for the relative frequency of headaches in first- and second-degree relatives. RESULTS: Out of 172, 84 (48.8%) children with headache had a migraine and 60 (34.9%) had tension headaches; 3 children (1.7%) had epilepsy or unprovoked seizures. Migraine and epilepsy, co-occurred in 2/84 (2.3%). Eight out of 70 patients with epilepsy had headaches (11.4%); none had migraine. Around 43% of patients with BCECTS or CAE had a family history of headache, more prevalent in first-degree relatives of children with BCECTS than CAE. CONCLUSION: Contrary to existing literature, migraine and epilepsy, co-occurred infrequently in these highly selected samples. Family history of headache was frequent in patients with BCECTS and CAE, without any significant difference between the two. PMID- 26854587 TI - Congenital Amegakaryocytic Thrombocytopenia Type II Presenting with Multiple Central Nervous System Anomalies. AB - Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare autosomal recessive bone marrow failure, caused by MPL gene mutations. The combination of CAMT and central nervous system abnormalities is uncommon. We describe a case with a homozygous missense MPL gene mutation and polymicrogyria, underdevelopment of the cerebellum, and multiple intracranial hemorrhages. PMID- 26854588 TI - Investigating the Victim Pseudomaturity Effect: How a Victim's Chronological Age and Dress Style Influences Attributions in a Depicted Case of Child Sexual Assault. AB - Three-hundred and seven members of the UK public read a hypothetical child sexual abuse case in which the victim's chronological age (12 versus 15 years old) and dress style (sexualized versus nonsexualized) were experimentally manipulated before completing 22 assault severity and blame attribution items. It was predicted that the 15-year-old and the sexually dressed victim would be blamed more for her own abuse. In addition, males were expected to be more blaming generally, but especially of the older and/or sexually dressed victim. Results were generally in line with predictions, highlighting the role seemingly controllable victim characteristics play in blaming child sexual abuse victims. Findings are discussed in relation to defensive attributions, gender stereotyping and the newly suggested victim pseudomaturity effect. Criminal justice, victim welfare, and rape myth implications together with methodological issues and ideas for future research work are also considered. PMID- 26854589 TI - The potential of targeting CYP11B. AB - INTRODUCTION: Members of the CYP11B subfamily participate in the biosynthesis of important steroid hormones. CYP11B1 catalyzes the formation of cortisol, while CYP11B2 realizes the biosynthesis of aldosterone. Overproduction of cortisol is related to Cushing's disease, whereas overproduction of aldosterone leads to hypertension and end-organ damage such as cardiac and renal hypertrophy. Therefore, CYP11B1 and CYP11B2 have been defined as interesting targets for the development of novel drugs. AREAS COVERED: The paper describes the CYP11B1 and CYP11B2 genes and proteins, giving special attention to their functional and structural properties, the development of efficient test systems for potential inhibitors of both CYPs and the development and testing of novel potential drugs on the basis of selective inhibition of CYP11B1 and CYP11B2. EXPERT OPINION: The availability of relevant and efficient screening systems for testing the effects of inhibitors of human CYP11B1 and CYP11B2, combined with experiences and success in synthesizing selective and efficient inhibitors of these isoenzymes, provides a realistic basis for a successful development of drugs using CYP11B1 and CYP11B2 as targets. The first clinical trials with the CYP11B2 inhibitor LCI699 demonstrated some side effects but showed inhibition of end-organ damage in animals, indicating that it might be a useful lead compound for future developments. PMID- 26854590 TI - Nitrite attenuated peroxynitrite and hypochlorite generation in activated neutrophils. AB - Oxidative stress is usually considered as an important factor to the pathogenesis of various diseases. Peroxynitrite (ONOO(-)) and hypochlorite (OCl(-)) are formed in immune cells as a part of the innate host defense system, but excessive reactive oxygen species generation can cause progressive inflammation and tissue damage. It has been proven that through mediating nitric oxide (NO) homeostasis, inorganic nitrite (NO2(-)) shows organ-protective effects on oxidative stress and inflammation. However, the effects of NO2(-) on the function of immune cells were still not clear. The potential role of NO2(-) in modulating ONOO(-) and OCl(-) generation in neutrophil cells was investigated in this study. As an immune cell activator, lipopolysaccharide (LPS) increased both ONOO(-) and OCl(-) production in neutrophils, which was significantly attenuated by NO2(-). NO2(-) reduced superoxide (O2(.-)) generation via a NO-dependent mechanism and increased NO formation in activated neutrophils, suggesting a crucial role of O2(.-) in NO2(-) mediated reduction of ONOO(-). Moreover, the reduced effect of NO2(-) on OCl(-) production was attributed to that NO2(-) reduced H2O2 production in activated neutrophils without influencing the release of myeloperoxidase (MPO), thus limiting OCl(-) production by MPO/H2O2 system. Therefore, NO2(-) attenuates ONOO( ) and OCl(-) formation in activated neutrophils, opening a new direction to modulate the inflammatory response. PMID- 26854591 TI - Glutaredoxin-deficiency confers bloodstream Trypanosoma brucei with improved thermotolerance. AB - As constituents of their unusual trypanothione-based thiol metabolism, African trypanosomes express two dithiol glutaredoxins (Grxs), a cytosolic Grx1 and a mitochondrial Grx2, with so far unknown biological functions. As revealed by gel shift assays, in the mammalian bloodstream form of Trypanosoma brucei, Grx1 is in the fully reduced state. Upon diamide treatment of the cells, Grx1 forms an active site disulfide bridge that is rapidly re-reduced after stress removal; Cys76, a conserved non-active site Cys remains in the thiol state. Deletion of both grx1 alleles does not result in any proliferation defect of neither the procyclic insect form nor the bloodstream form, even not under various stress conditions. In addition, the Grx1-deficient parasites are fully infectious in the mouse model. A functional compensation by Grx2 is unlikely as identical levels of Grx2 were found in wildtype and Grx1-deficient cells. In the classical hydroxyethyl disulfide assay, Grx1-deficient bloodstream cells display 50-60% of the activity of wildtype cells indicating that the cytosolic oxidoreductase accounts for a major part of the total deglutathionylation capacity of the parasite. Intriguingly, at elevated temperature, proliferation of the Grx1 deficient bloodstream parasites is significantly less affected compared to wildtype cells. When cultured for three days at 39 degrees C, only 51% of the cells in the wildtype population retained normal morphology with single mitochondrial and nuclear DNA (1K1N), whereas 27% of the cells displayed >=2K2N. In comparison, 64% of the Grx1-deficient cells kept the 1K1N phenotype and only 18% had >=2K2N. The data suggest that Grx1 plays a role in the regulation of the thermotolerance of the parasites by (in)directly interfering with the progression of the cell cycle, a process that may comprise protein (de)glutathionylation step(s). PMID- 26854592 TI - Juvenile idiopathic arthritis and future risk for cardiovascular disease: a multicenter study. AB - OBJECTIVES: To evaluate the frequency of cardiovascular disease (CVD) and CVD risk factor development in adult patients previously diagnosed with juvenile idiopathic arthritis (JIA). METHOD: A cohort study was conducted utilizing patients at two academic institutions (cohorts 1 and 2). Each institution evaluated the common endpoint of CVD outcomes and CVD risk factor development in adults aged >= 30 years and at the 29-year follow-up from disease onset in cohorts 1 and 2, respectively, with comparison to control groups of similar age and sex. RESULTS: Cohort 1 included 41 patients with JIA and follow-up >= 30 years of age with comparison to 41 controls. Three patients (7%) had CVD, compared to one control (2%; p = 0.31). Cohort 2 included 170 patients with JIA and a median of 29 years of follow-up from disease onset with comparison to 91 controls. Two patients (2%) had CVD, compared to none of the controls (p = 0.29). The presence of CVD risk factors was found to be increased in the JIA group compared to the controls in three categories: family history of CVD (cohort 1), hypertension (cohort 2), and ever smokers (cohorts 2). CONCLUSIONS: There is no increase in CVD events in patients with JIA 29 years following disease onset when compared to the general population. As these cohorts age, it will be informative to evaluate whether this baseline risk remains present or a trend towards increasing CVD emerges. Continued longitudinal follow-up of these cohorts and larger population-based studies are needed to establish a definitive relationship between JIA and CVD. PMID- 26854593 TI - Y-shaped probe for convenient and label-free detection of microRNA-21 in vitro. AB - A simple, highly selective, and label-free microRNA (miRNA) detection method based on l-alanine-reduced graphene oxide fluorescence quenching with a Y-shaped probe is proposed. The Y-shaped probe was synthesized by silver nitrate and a cytosine-rich molecular beacon (MB) in two terminals through sodium borohydride reduction, which generated a stronger fluorescent signal than ordinary DNA templated silver nanoclusters (AgNCs). Meanwhile, the Y-shaped probe contained a single-stranded loop structure, which could be superbly adsorbed onto the surface of reduced graphene oxide (RGO) via pi-pi stacking interaction, and this special structure of the probe was designed to improve its sensitivity and selectivity. In addition, the quenching capacities of graphene oxide (GO) and RGO were compared in this research. The strong interaction between nucleobases of the loop structure and RGO nanosheet made the MB-AgNCs-RGO system exhibit minimal background fluorescence. In the presence of miRNA-21, the loop structure of the Y shaped probe can hybridize with target miRNA-21; the molecular beacon encapsulated probe is far away from RGO surface and produces a detectable signal. The MB-AgNCs based approach provides a label-free avenue to detect miRNA with high selectivity and good reproducibility, which has a promising application in early clinical diagnosis and biomedical research. PMID- 26854594 TI - The role of negative reinforcement eating expectancies in the relation between experiential avoidance and disinhibition. AB - OBJECTIVES: Eating-related disinhibition (i.e., a tendency to overeat in response to various stimuli) is associated with weight gain and poorer long-term weight loss success. Theoretically, experiential avoidance (i.e., the desire or attempts to avoid uncomfortable internal experiences), may predispose individuals to developing negative reinforcement eating expectancies (i.e., the belief that eating will help to mitigate distress), which in turn promote disinhibition. Such relationships are consistent with an acquired preparedness model, which posits that dispositions influence learning and subsequent behavior. Drawing from this framework, the current study represents the first investigation of relations between negative reinforcement eating expectancies, experiential avoidance (both general and food-specific) and disinhibited eating. In particular, the mediating role of negative reinforcement eating expectancies in the relation between experiential avoidance and disinhibited eating was examined. METHOD: Participants (N=107) were overweight and obese individuals presenting for behavioral weight loss treatment who completed measures of general and food-related experiential avoidance, negative reinforcement eating expectancies, and disinhibition. RESULTS: Experiential avoidance and negative reinforcement eating expectancies significantly related to disinhibition. Furthermore, the relation between experiential avoidance and disinhibition was mediated by negative reinforcement eating expectancies. DISCUSSION: The current study supports an acquired preparedness model for disinhibition, such that the relation between experiential avoidance and disinhibition is accounted for by expectations that eating will alleviate distress. Findings highlight the potential role of eating expectancies in models accounting for obesity risk, and identify negative reinforcement eating expectancies as a potential treatment target for reducing disinhibition. PMID- 26854595 TI - EPAC activation inhibits acetaldehyde-induced activation and proliferation of hepatic stellate cell via Rap1. AB - Hepatic stellate cells (HSCs) activation represents an essential event during alcoholic liver fibrosis (ALF). Previous studies have demonstrated that the rat HSCs could be significantly activated after exposure to 200 MUmol/L acetaldehyde for 48 h, and the cAMP/PKA signaling pathways were also dramatically upregulated in activated HSCs isolated from alcoholic fibrotic rat liver. Exchange protein activated by cAMP (EPAC) is a family of guanine nucleotide exchange factors (GEFs) for the small Ras-like GTPases Rap, and is being considered as a vital mediator of cAMP signaling in parallel with the principal cAMP target protein kinase A (PKA). Our data showed that both cAMP/PKA and cAMP/EPAC signaling pathways were involved in acetaldehyde-induced HSCs. Acetaldehyde could reduce the expression of EPAC1 while enhancing the expression of EPAC2. The cAMP analog Me-cAMP, which stimulates the EPAC/Rap1 pathway, could significantly decrease the proliferation and collagen synthesis of acetaldehyde-induced HSCs. Furthermore, depletion of EPAC2, but not EPAC1, prevented the activation of HSC measured as the production of alpha-SMA and collagen type I and III, indicating that EPAC1 appears to have protective effects on acetaldehyde-induced HSCs. Curiously, activation of PKA or EPAC perhaps has opposite effects on the synthesis of collagen and alpha-SMA: EPAC activation by Me-cAMP increased the levels of GTP bound (activated) Rap1 while PKA activation by Phe-cAMP had no significant effects on such binding. These results suggested that EPAC activation could inhibit the activation and proliferation of acetaldehyde-induced HSCs via Rap1. PMID- 26854596 TI - A Systematic Meta-Analysis of Toxoplasma gondii Prevalence in Food Animals in the United States. AB - Toxoplasma gondii is a widely distributed protozoan parasite. The Centers for Disease Control and Prevention reported that T. gondii is one of three pathogens (along with Salmonella and Listeria), that together account for >70% of all deaths due to foodborne illness in the United States. Food animals are reservoirs for T. gondii and act as one of the sources for parasite transmission to humans. Based on limited population-based data, the Food and Agriculture Organization/World Health Organization estimated that approximately 22% of human T. gondii infections are meatborne. The objective of the current study was to conduct a systematic meta-analysis to provide a precise estimation of T. gondii infection prevalence in food animals produced in the United States. Four databases were searched to collect eligible studies. Prevalence was estimated in six animal categories (confinement-raised market pigs, confinement-raised sows, non-confinement-raised pigs, lamb, goats, and non-confinement-raised chickens) by a quality-effects model. A wide variation in prevalence was observed in each animal category. Animals raised outdoors or that have outdoor access had a higher prevalence as compared with animals raised indoors. T. gondii prevalence in non confinement-raised pigs ranked the highest (31.0%) followed by goats (30.7%), non confinement-raised chickens (24.1%), lambs (22.0%), confinement-raised sows (16.7%), and confinement-raised market pigs (5.6%). These results indicate that T. gondii-infected animals are a food safety concern. The computed prevalence can be used as an important input in quantitative microbial risk assessment models to further predict public health burden. PMID- 26854597 TI - Islet-after-failed-pancreas and pancreas-after-failed islet transplantation: Two complementary rescue strategies to control diabetes. AB - For selected patients with type 1 diabetes, beta-cell replacement is the treatment of choice, either by islet transplantation (ITX) or whole pancreas transplantation (PTX). When either modality fails, current practice is to consider retransplantation, or return to exogenous insulin. We investigate outcomes with PTX after failed ITX (PAI), and ITX after failed PTX (IAP). All patients receiving PAI or IAP at a single institution were identified. Donor and recipient variables were documented, including transplant outcomes analyzed for insulin requirement and metabolic control. Five subjects were listed for PAI, and 2 received transplants. Of the 4 listed for IAP, 3 have received transplants. The mean waitlist time was 4.5 +/- 4.1 y for PAI and 0.35 +/-0 .4 y for IAP (p = 0.08). Metabolic control was excellent after PAI, with 2/2 insulin-independent. After IAP, 1/2 achieved insulin independence and good metabolic control after 2 islet infusions. The third could not receive 2(nd) infusion and presented c peptide levels < 0.1 nmol/L. Both strategies are feasible. The outcomes after PAI in our center must be offset by much longer waitlist time due to the sensitization status of these patients. Data from multicentre experience will allow more robust comparative outcomes to be made, the current observations being restricted to a limited patient set. PMID- 26854598 TI - Emerging drugs to treat glaucoma: targeting prostaglandin F and E receptors. AB - INTRODUCTION: Commercially available prostaglandin analogues (PGAs) activate the prostaglandin F receptor (FP) reducing intraocular pressure (IOP), thereby stabilizing glaucomatous optic neuropathy. Poor adherence with eye drops and intolerance impact treatment success. AREAS COVERED: We review developments in drug formulation and delivery, including punctal plugs, topical ring inserts, subconjunctival injections and inserts, and intraocular inserts. We also outline research into new fixed dose combinations that include prostaglandin analogues and preservative-free versions of established agents. EXPERT OPINION: Glaucoma is a chronic, usually progressive disease that causes irreversible visual loss. As its prevalence increases exponentially with age, it has significant implications as the population ages. Health resources need to meet increased demand for glaucoma management resources, including monitoring and treating glaucoma suspects and patients and supporting those who have suffered visual disability. Several promising therapies are under investigation. Sustained-release prostaglandin analogues using alternate delivery methods are encouraging. Delivery routes may be more invasive than topical drops. Nanotechnological release delivery of prostaglandin analogues could lower IOP effectively. Approaches like this would eliminate many of the adherence issues associated with daily topical PGA eye drop use. PMID- 26854599 TI - Ethical considerations in gene therapy. PMID- 26854601 TI - GprotPRED: Annotation of Galpha, Gbeta and Ggamma subunits of G-proteins using profile Hidden Markov Models (pHMMs) and application to proteomes. AB - Heterotrimeric G-proteins form a major protein family, which participates in signal transduction. They are composed of three subunits, Galpha, Gbeta and Ggamma. The Galpha subunit is further divided in four distinct families Gs, Gi/o, Gq/11 and G12/13. The goal of this work was to detect and classify members of the four distinct families, plus the Gbeta and the Ggamma subunits of G-proteins from sequence alone. To achieve this purpose, six specific profile Hidden Markov Models (pHMMs) were built and checked for their credibility. These models were then applied to ten (10) proteomes and were able to identify all known G-protein and classify them into the distinct families. In a separate case study, the models were applied to twenty seven (27) arthropod proteomes and were able to give more credible classification in proteins with uncertain annotation and in some cases to detect novel proteins. An online tool, GprotPRED, was developed that uses these six pHMMs. The sensitivity and specificity for all pHMMs were equal to 100% with the exception of the Gbeta case, where sensitivity equals to 100%, while specificity is 99.993%. In contrast to Pfam's pHMM which detects Galpha subunits in general, our method not only detects Galpha subunits but also classifies them into the appropriate Galpha-protein family and thus could become a useful tool for the annotation of G-proteins in newly discovered proteomes. GprotPRED online tool is publicly available for non-commercial use at http://bioinformatics.biol.uoa.gr/GprotPRED and, also, a standalone version of the tool at https://github.com/vkostiou/GprotPRED. PMID- 26854600 TI - Analysis of differentially expressed proteins in Yersinia enterocolitica-infected HeLa cells. AB - Yersinia enterocolitica is a facultative intracellular pathogen and a causative agent of yersiniosis, which can be contracted by ingestion of contaminated food. Yersinia secretes virulence factors to subvert critical pathways in the host cell. In this study we utilized shotgun label-free proteomics to study differential protein expression in epithelial cells infected with Y.enterocolitica. We identified a total of 551 proteins, amongst which 42 were downregulated (including Prostaglandin E Synthase 3, POH-1 and Karyopherin alpha) and 22 were upregulated (including Rab1 and RhoA) in infected cells. We validated some of these results by western blot analysis of proteins extracted from Caco-2 and HeLa cells. The proteomic dataset was used to identify host canonical pathways and molecular functions modulated by this infection in the host cells. This study constitutes a proteome of Yersinia-infected cells and can support new discoveries in the area of host-pathogen interactions. STATEMENT OF SIGNIFICANCE OF THE STUDY: We describe a proteome of Yersinia enterocolitica-infected HeLa cells, including a description of specific proteins differentially expressed upon infection, molecular functions as well as pathways altered during infection. This proteomic study can lead to a better understanding of Y. enterocolitica pathogenesis in human epithelial cells. PMID- 26854602 TI - Abeta-affected pathogenic induction of S-nitrosylation of OGT and identification of Cys-NO linkage triplet. AB - Mechanistic link of protein hypo-O-GlcNAcylation to the pathogenesis of Alzheimer's disease (AD) remains unclear. Here, we found that S-nitrosylation of O-linked N-acetylglucosaminyltransferase (SNO-OGT) was induced by beta-amyloid peptide (Abeta) exposure to SK-N-MC and SK-N-SH human neuroblastoma cells. Subsequently, Abeta-induced SNO-OGT led to protein hypo-O-GlcNAcylation globally including tau hypo-O-GlcNAcylation. Our results support that underlying mechanism for induction of SNO-OGT comprises the concerted action of Abeta-triggered Ca2+ entry into cells and nNOS-catalyzed NO production. Intriguingly, OGT was found to be associated with nNOS and its association was enhanced during Abeta treatment. In parallel with SNO-OGT-mediated tau hypo-O-GlcNAcylation, Abeta led to SNO-Akt mediated GSK3beta activation for tau phosphorylation, suggesting that tau hyperphosphorylation is established by synergistic connection between SNO-OGT and GSK3beta activation. We also observed that Abeta-neurotoxicity including both reactive oxygen species (ROS) production and cell death was amplified with DON treatment, whereas it was restored by PUGNAc treatment, GlcNH2 treatment or OGT overexpression. Early time-course Abeta-monitoring assay revealed that premaintained hyper-O-GlcNAcylation inside cells blocked not only Abeta-triggered Ca2+ entry into cells but also induction of SNO-OGT and SNO-Akt. Together, these findings suggest that induction of SNO-OGT by Abeta exposure is a pathogenic mechanism to cause cellular hypo-O-GlcNAcylation by which Abeta neurotoxicity is executed, and conversely, hyper-O-GlcNAcylation within cells can defend against Abeta neurotoxicity. Furthermore, our Cys mapping demonstrates that cysteine nitric oxide (Cys-NO) linkages in SNO-OGT occur at triple Cys845, Cys921, and Cys965 residues in C-terminal catalytic domain (C-CAT), suggesting that Cys-NO linkage triplet in SNO-OGT is associated with null OGT activity. PMID- 26854603 TI - Murine erythroid 5-aminolevulinate synthase: Truncation of a disordered N terminal extension is not detrimental for catalysis. AB - 5-Aminolevulinate synthase (ALAS), a pyridoxal 5'-phosphate (PLP)-dependent homodimeric enzyme, catalyzes the initial step of heme biosynthesis in non-plant eukaryotes. The precursor form of the enzyme is translated in the cytosol, and upon mitochondrial import, the N-terminal targeting presequence is proteolytically cleaved to generate mature ALAS. In bone marrow-derived erythroid cells, a mitochondrial- and site-specific endoprotease of yet unknown primary structure, produces a protein shorter than mature erythroid ALAS (ALAS2) found in peripheral blood erythroid cells. This truncated ALAS2 lacks the presequence and the N-terminal sequence (corresponding to ~7 KDa molecular mass) present in ALAS2 from peripheral blood erythroid cells. How the truncation affects the structural topology and catalytic properties of ALAS2 is presently not known. To address this question, we created a recombinant, truncated, murine ALAS2 (DeltamALAS2) devoid of the cleavable N-terminal region and examined its catalytic and biophysical properties. The N-terminal truncation of mALAS2 did not significantly affect the organization of the secondary structure, but a subtle reduction in the rigidity of the tertiary structure was noted. Furthermore, thermal denaturation studies revealed a decrease of 4.3 degrees C in the Tm value of DeltamALAS2, implicating lower thermal stability. While the kcat of DeltamALAS2 is slightly increased over that of the wild-type enzyme, the slowest step in the DeltamALAS2 catalyzed reaction remains dominated by ALA release. Importantly, intrinsic disorder algorithms imply that the N-terminal region of mALAS2 is highly disordered, and thus susceptible to proteolysis. We propose that the N-terminal truncation offers a cell-specific ALAS2 regulatory mechanism without hindering heme synthesis. PMID- 26854604 TI - Electrochemical disinfection of toilet wastewater using wastewater electrolysis cell. AB - The paucity of proper sanitation facilities has contributed to the spread of waterborne diseases in many developing countries. The primary goal of this study was to demonstrate the feasibility of using a wastewater electrolysis cell (WEC) for toilet wastewater disinfection. The treated wastewater was designed to reuse for toilet flushing and agricultural irrigation. Laboratory-scale electrochemical (EC) disinfection experiments were performed to investigate the disinfection efficiency of the WEC with four seeded microorganisms (Escherichia coli, Enterococcus, recombinant adenovirus serotype 5, and bacteriophage MS2). In addition, the formation of organic disinfection byproducts (DBPs) trihalomethanes (THMs) and haloacetic acids (HAA5) at the end of the EC treatment was also investigated. The results showed that at an applied cell voltage of +4 V, the WEC achieved 5-log10 reductions of all four seeded microorganisms in real toilet wastewater within 60 min. In contrast, chemical chlorination (CC) disinfection using hypochlorite [NaClO] was only effective for the inactivation of bacteria. Due to the rapid formation of chloramines, less than 0.5-log10 reduction of MS2 was observed in toilet wastewater even at the highest [NaClO] dosage (36 mg/L, as Cl2) over a 1 h reaction. Experiments using laboratory model waters showed that free reactive chlorine generated in situ during EC disinfection process was the main disinfectant responsible for the inactivation of microorganisms. However, the production of hydroxyl radicals [OH], and other reactive oxygen species by the active bismuth-doped TiO2 anode were negligible under the same electrolytic conditions. The formation of THMs and HAA5 were found to increase with higher applied cell voltage. Based on the energy consumption estimates, the WEC system can be operated using solar energy stored in a DC battery as the sole power source. PMID- 26854605 TI - Inhibition of biofilm formation by D-tyrosine: Effect of bacterial type and D tyrosine concentration. AB - D-Tyrosine inhibits formation and triggers disassembly of bacterial biofilm and has been proposed for biofouling control applications. This study probes the impact of D-tyrosine in different biofilm formation stages in both G+ and G- bacteria, and reveals a non-monotonic correlation between D-tyrosine concentration and biofilm inhibition effect. In the attachment stage, cell adhesion was studied in a flow chamber, where D-tyrosine caused significant reduction in cell attachment. Biofilms formed by Pseudomonas aeruginosa and Bacillus subtilis were characterized by confocal laser scanning microscopy as well as quantitative analysis of cellular biomass and extracellular polymeric substances. D-Tyrosine exhibited strong inhibitive effects on both biofilms with an effective concentration as low as 5 nM; the biofilms responded to D-tyrosine concentration change in a non-monotonic, bi-modal pattern. In addition, D tyrosine showed notable and different impact on EPS production by G+ and G- bacteria. Extracellular protein was decreased in P. aeruginosa biofilms, but increased in those of B. subtilis. Exopolysaccharides production by P. aeruginosa was increased at low concentrations and reduced at high concentrations while no impact was found in B. subtilis. These results suggest that distinct mechanisms are at play at different D-tyrosine concentrations and they may be species specific. Dosage of D-tyrosine must be carefully controlled for biofouling control applications. PMID- 26854606 TI - Granular activated carbon adsorption of organic micro-pollutants in drinking water and treated wastewater--Aligning breakthrough curves and capacities. AB - Small-scale granular activated carbon (GAC) tests for the adsorption of organic micro-pollutants (OMP) were conducted with drinking water and wastewater treatment plant (WWTP) effluent. In both waters, three influent OMP concentration levels were tested. As long as the influent OMP concentrations are below certain thresholds, the relative breakthrough behavior is not impacted in the respective water. Accordingly, the GAC capacity for OMP is directly proportional to the influent OMP concentration in the corresponding water. The differences between the OMP breakthrough curves in drinking water and WWTP effluent can be attributed to the concentrations of the low molecular weight acid and neutral (LMW) organics of the waters. Presenting the relative OMP concentrations (c/c0) over the specific throughput of the LMW organics (mg LMW organics/g GAC), the OMP breakthrough curves in drinking water and WWTP effluent superimpose each other. This superimposition can be further increased if the UV absorbance at 254 nm (UV254) of the LMW organics is considered. In contrast, using the specific throughput of the dissolved organic carbon (DOC) did not suffice to obtain superimposed breakthrough curves. Thus, the LMW organics are the major water constituent impacting OMP adsorption onto GAC. The results demonstrate that knowing the influent OMP and LMW organics concentrations (and UV254) of different waters, the OMP breakthroughs and GAC capacities corresponding to any water can be applied to all other waters. PMID- 26854608 TI - The influence of a non-aqueous phase liquid (NAPL) and chemical oxidant application on perfluoroalkyl acid (PFAA) fate and transport. AB - One dimensional column experiments were conducted using saturated porous media containing residual trichloroethylene (TCE) to understand the effects of non aqueous phase liquids (NAPLs) and chemical oxidation on perfluoroalkyl acid (PFAA) fate and transport. Observed retardation factors and data from supporting batch studies suggested that TCE provides additional sorption capacity that can increase PFAA retardation (i.e., decreased mobility), though the mechanisms remain unclear. Treatment with persulfate activated with FeCl2 and citric acid, catalyzed hydrogen peroxide (CHP), or permanganate did not result in oxidative transformations of PFAAs. However, impacts on PFAA sorption were apparent, and enhanced sorption was substantial in the persulfate-treated columns. In contrast, PFAA transport was accelerated in permanganate- and CHP-treated columns. Ultimately, PFAA transport in NAPL contaminated groundwater is likely influenced by porous media properties, NAPL characteristics, and water quality properties, each of which can change due to chemical oxidant treatment. For contaminated sites for which ISCO is a viable treatment option, changes to PFAA transport and the implications thereof should be included as a component of the remediation evaluation and selection process. PMID- 26854607 TI - A new adsorption-elution technique for the concentration of aquatic extracellular antibiotic resistance genes from large volumes of water. AB - Extracellular antibiotic resistance genes (eARGs) that help in the transmission and spread of antibiotic-resistant bacteria are emerging environmental contaminants in water, and there is therefore a growing need to assess environmental levels and associated risks of eARGs. However, as they are present in low amounts, it is difficult to detect eARGs in water directly with PCR techniques. Here, we prepared a new type of nucleic acid adsorption particle (NAAP) with high capacity and developed an optimal adsorption-elution method to concentrate eARGs from large volumes of water. With this technique, we were able to achieve an eARG recovery rate of above 95% from 10 L of water samples. Moreover, combining this new method with quantitative real-time PCR (qPCR), the sensitivity of the eARG detection was 10(4) times that of single qPCR, with the detection limit lowered to 100 gene copies (GCs)/L. Our analyses showed that the eARG load, virus load and certain water characteristics such as pH, chemical oxygen demand (CODMn), and turbidity affected the eARGs recovery rate. However, high eARGs recovery rates always remained within the standard limits for natural surface water quality, while eARG levels in water were lower than the detection limits of single qPCR assays. The recovery rates were not affected by water temperature and heterotrophic plate counts (HPC). The eARGs whatever located in the plasmids or the short-length linear DNAs can be recovered from the water. Furthermore, the recovery rate was high even in the presence of high concentrations of plasmids in different natural water (Haihe river, well water, raw water for drinking water, Jinhe river, Tuanbo lake and the Yunqiao reservoir). By this technology, eARGs concentrations were found ranging from (2.70 +/- 0.73) * 10(2) to (4.58 +/- 0.47) * 10(4) GCs/L for the extracellular ampicillin resistance gene and (5.43 +/- 0.41) * 10(2) to (2.14 +/- 0.23) * 10(4) GCs/L for the extracellular gentamicin resistance gene in natural water for the first time, respectively. All these findings suggest that NAAPs have great potential for the monitoring of eARGs pollution in water. PMID- 26854609 TI - Compensation for egg donation: a zero-sum game. PMID- 26854610 TI - Identification of possible siRNA molecules for TDP43 mutants causing amyotrophic lateral sclerosis: In silico design and molecular dynamics study. AB - The DNA binding protein, TDP43 is a major protein involved in amyotrophic lateral sclerosis and other neurological disorders such as frontotemporal dementia, Alzheimer disease, etc. In the present study, we have designed possible siRNAs for the glycine rich region of tardbp mutants causing ALS disorder based on a systematic theoretical approach including (i) identification of respective codons for all mutants (reported at the protein level) based on both minimum free energy and probabilistic approaches, (ii) rational design of siRNA, (iii) secondary structure analysis for the target accessibility of siRNA, (iii) determination of the ability of siRNA to interact with mRNA and the formation/stability of duplex via molecular dynamics study for a period of 15ns and (iv) characterization of mRNA-siRNA duplex stability based on thermo-physical analysis. The stable GC-rich siRNA expressed strong binding affinity towards mRNA and forms stable duplex in A form. The linear dependence between the thermo-physical parameters such as Tm, GC content and binding free energy revealed the ability of the identified siRNAs to interact with mRNA in comparable to that of the experimentally reported siRNAs. Hence, this present study proposes few siRNAs as the possible gene silencing agents in RNAi therapy based on the in silico approach. PMID- 26854611 TI - Molecular Electrical Doping of Organic Semiconductors: Fundamental Mechanisms and Emerging Dopant Design Rules. AB - Today's information society depends on our ability to controllably dope inorganic semiconductors, such as silicon, thereby tuning their electrical properties to application-specific demands. For optoelectronic devices, organic semiconductors, that is, conjugated polymers and molecules, have emerged as superior alternative owing to the ease of tuning their optical gap through chemical variability and their potential for low-cost, large-area processing on flexible substrates. There, the potential of molecular electrical doping for improving the performance of, for example, organic light-emitting devices or organic solar cells has only recently been established. The doping efficiency, however, remains conspicuously low, highlighting the fact that the underlying mechanisms of molecular doping in organic semiconductors are only little understood compared with their inorganic counterparts. Here, we review the broad range of phenomena observed upon molecularly doping organic semiconductors and identify two distinctly different scenarios: the pairwise formation of both organic semiconductor and dopant ions on one hand and the emergence of ground state charge transfer complexes between organic semiconductor and dopant through supramolecular hybridization of their respective frontier molecular orbitals on the other hand. Evidence for the occurrence of these two scenarios is subsequently discussed on the basis of the characteristic and strikingly different signatures of the individual species involved in the respective doping processes in a variety of spectroscopic techniques. The critical importance of a statistical view of doping, rather than a bimolecular picture, is then highlighted by employing numerical simulations, which reveal one of the main differences between inorganic and organic semiconductors to be their respective density of electronic states and the doping induced changes thereof. Engineering the density of states of doped organic semiconductors, the Fermi-Dirac occupation of which ultimately determines the doping efficiency, thus emerges as key challenge. As a first step, the formation of charge transfer complexes is identified as being detrimental to the doping efficiency, which suggests sterically shielding the functional core of dopant molecules as an additional design rule to complement the requirement of low ionization energies or high electron affinities in efficient n-type or p-type dopants, respectively. In an extended outlook, we finally argue that, to fully meet this challenge, an improved understanding is required of just how the admixture of dopant molecules to organic semiconductors does affect the density of states: compared with their inorganic counterparts, traps for charge carriers are omnipresent in organic semiconductors due to structural and chemical imperfections, and Coulomb attraction between ionized dopants and free charge carriers is typically stronger in organic semiconductors owing to their lower dielectric constant. Nevertheless, encouraging progress is being made toward developing a unifying picture that captures the entire range of doping induced phenomena, from ion-pair to complex formation, in both conjugated polymers and molecules. Once completed, such a picture will provide viable guidelines for synthetic and supramolecular chemistry that will enable further technological advances in organic and hybrid organic/inorganic devices. PMID- 26854612 TI - Synergistic enhancement of tolerance mechanisms in response to photoactivation of cationic tetra (N-methylpyridyl) porphyrins in tomato plantlets. AB - Antimicrobial photodynamic treatment (APDT) is largely used in medical domain and could be envisaged as a farming practice against crop pathogens such as bacteria and fungi that generate drops in agricultural yields. Thus, as a prerequisite for this potential application, we studied the effect of water-soluble anionic (TPPS and Zn-TPPS) and cationic (TMPyP and Zn-TMPyP) porphyrins tested on tomato (Solanum lycopersicum) plantlets grown in vitro under a 16 h photoperiod. First of all, under dark conditions, none of the four porphyrins inhibited germination and induced cytotoxic effects on tomato plantlets as etiolated development was not altered. The consequences of porphyrin long-term photoactivation (14 days) were thus studied on in vitro-grown tomato plantlets at phenotypic and molecular levels. Cationic porphyrins especially Zn-TMPyP were the most efficient photosensitizers and dramatically altered growth without killing plantlets. Indeed, tomato plantlets were rescued after cationic porphyrins treatment. To gain insight, the different molecular ways implied in the plantlet tolerance to photoactivated Zn-TMPyP, lipid peroxidation, antioxidative molecules (total thiols, proline, ascorbate), and ROS detoxification enzymes were evaluated. In parallel to an increase in lipid peroxidation and hydrogen peroxide production, antioxidative molecules and enzymes (guaiacol peroxidase, catalase, and superoxide dismutase) were up-regulated in root apparatus in response to photoactivated Zn-TMPyP. This study showed that tomato plantlets could overcome the pressure triggered by photoactivated cationic porphyrin by activating antioxidative molecule and enzyme arsenal and confining Zn-TMPyP into cell wall and/or apoplasm, suggesting that APDT directed against tomato pathogens could be envisaged in the future. PMID- 26854613 TI - Perturbation of pharmacologically relevant polyphenolic compounds in Moringa oleifera against photo-oxidative damages imposed by gamma radiation. AB - Oxidative stress is a physiological state associated with almost all biotic and abiotic stresses in plants. This phenomenon occurs due to imbalances which result from the overproduction of reactive oxygen species (ROS). Plants, however, have developed sophisticated mechanisms to mitigate the effect of ROS. In this regard, plant polyphenolic metabolites such as flavonoids are known to possess high antioxidant activities. In the current study, changes in the levels of phenolic compounds from Moringa oleifera after gamma radiation treatment were investigated with reverse phase liquid chromatography and mass spectrometric techniques in combination with multivariate data models such as principal component analysis and orthogonal projection to latent structures discriminant analysis. Our results revealed several polyphenolic compounds such as hydroxycinnamoyl derivatives and flavonoid molecules to be down-regulated post-radiation treatment. Interestingly, other flavonoid molecules were found to be up-regulated post-radiation treatment, thereby suggesting a possible compensatory phenomenon. The existence and involvement of structurally similar metabolites (such as regio-isomers of chlorogenic acids) in M. oleifera towards mitigating photo-oxidative damages are in support of the proposed evolutionary existence of a large pool of polyphenolics which contribute to the state of readiness, aptly described as a "better safe than sorry" phenomenon. Our study thus reaffirms the involvement of phenolic compounds as a first line of constitutive/preformed protection against oxidative stress. Furthermore, the obtained data supports M. oleifera as a source of versatile and pharmacologically relevant metabolites that may be exploited for ameliorating the oxidative damages imposed by several metabolic disorders in humans. PMID- 26854614 TI - PPIP5K1 interacts with the exocyst complex through a C-terminal intrinsically disordered domain and regulates cell motility. AB - Cellular signaling involves coordinated regulation of many events. Scaffolding proteins are crucial regulators of cellular signaling, because they are able to affect numerous events by coordinating specific interactions among multiple protein partners in the same pathway. Scaffolding proteins often contain intrinsically disordered regions (IDR) that facilitate the formation and function of distinct protein complexes. We show that PPIP5K1 contains an unusually long and evolutionarily conserved IDR. To investigate the biological role(s) of this domain, we identified interacting proteins using affinity purification coupled with mass spectrometry. Here, we report that PPIP5K1 is associated with a network of proteins that regulate vesicle-mediated transport. We further identified exocyst complex component 1 as a direct interactor with the IDR of PPIP5K1. Additionally, we report that knockdown of PPIP5K1 decreases motility of HeLa cells in a wound-healing assay. These results suggest that PPIP5K1 might play an important role in regulating function of exocyst complex in establishing cellular polarity and directional migration of cells. PMID- 26854615 TI - N-Acetylgalactosamine Block-co-Polycations Form Stable Polyplexes with Plasmids and Promote Liver-Targeted Delivery. AB - The liver is an ideal target for nucleic acid therapeutic applications (i.e., siRNA, gene therapy, and genome editing) due to its ability to secrete proteins into the blood. In this work, we present the first synthesis of a novel monomer derived from N-acetyl-d-galactosamine (GalNAc) and its polymerization as a facile route to create multivalent delivery vehicles with exceptional targeting efficiency to asialoglycoprotein receptors (ASGPRs) on liver hepatocytes. A series of cationic diblock GalNAc glycopolymers composed of a GalNAc-derived block of fixed length (n = 62) and cationic 2-aminoethylmethacrylamide (AEMA) blocks of varying lengths (n = 19, 33, and 80) have been synthesized and characterized. In addition, nontargeted control polymers consisting of either glucose or polyethylene glycol-derived neutral blocks with an AEMA cationic block were also created and examined. All polymeric vehicles were able to bind and encapsulate plasmids (pDNA) into polymer-pDNA complexes (polyplexes). The GalNAc derived polyplexes were colloidally stable and maintained their size over a period of 4 h in reduced-serum cell culture media. The GalNAc-derived homopolymer effectively inhibited the uptake of Cy5-labeled asialofetuin (a natural ligand of ASGPRs) by cultured hepatocyte (HepG2) cells at lower concentrations (IC50 = 20 nM) than monomeric GalNAc (IC50 = 1 mM) and asialofetuin (IC50 = 1 MUM), suggesting highly enhanced ASGPR binding due to multivalency. These polymers also showed cell type-specific gene expression in cultured cells, with higher protein expression in ASGPR-presenting HepG2 than HeLa cells, which lack the receptor. Biodistribution studies in mice show higher accumulation of pDNA and GalNAc derived polymers in the liver compared with the glucose-derived nontargeted control. This study demonstrates the first facile synthesis of a multivalent GalNAc-derived block copolymer architecture that promotes enhanced delivery to liver and offers insights to improve targeted nanomedicines for a variety of applications. PMID- 26854616 TI - TiO2 Nanotubes with Open Channels as Deactivation-Resistant Photocatalyst for the Degradation of Volatile Organic Compounds. AB - We synthesized ordered TiO2 nanotubes (TNT) and compared their photocatalytic activity with that of TiO2 nanoparticles (TNP) film during the repeated cycles of photocatalytic degradation of gaseous toluene and acetaldehyde to test the durability of TNT as an air-purifying photocatalyst. The photocatalytic activity of TNT showed only moderate reduction after the five cycles of toluene degradation, whereas TNP underwent rapid deactivation as the photocatalysis cycles were repeated. Dynamic SIMS analysis showed that carbonaceous deposits were formed on the surface of TNP during the photocatalytic degradation of toluene, which implies that the photocatalyst deactivation should be ascribed to the accumulation of recalcitrant degradation intermediates (carbonaceous residues). In more oxidizing atmosphere (100% O2 under which less carbonaceous residues should form), the photocatalytic activity of TNP still decreased with repeating cycles of toluene degradation, whereas TNT showed no sign of deactivation. Because TNT has a highly ordered open channel structure, O2 molecules can be more easily supplied to the active sites with less mass transfer limitation, which subsequently hinders the accumulation of carbonaceous residues on TNT surface. Contrary to the case of toluene degradation, both TNT and TNP did not exhibit any significant deactivation during the photocatalytic degradation of acetaldehyde, because the generation of recalcitrant intermediates from acetaldehyde degradation is insignificant. The structural characteristics of TNT is highly advantageous in preventing the catalyst deactivation during the photocatalytic degradation of aromatic compounds. PMID- 26854617 TI - Neutrophils contribute to fracture healing by synthesizing fibronectin+ extracellular matrix rapidly after injury. AB - The role of inflammatory cells in bone regeneration remains unclear. We hypothesize that leukocytes contribute to fracture healing by rapidly synthesizing an "emergency extracellular matrix (ECM)" before stromal cells infiltrate the fracture hematoma (FH) and synthesize the eventual collagenous bone tissue. 53 human FHs were isolated at different time points after injury, ranging from day 0 until day 23 after trauma and stained using (immuno)histochemistry. FHs isolated within 48 h after injury contained fibronectin(+) ECM, which increased over time. Neutrophils within the early FHs stained positive for cellular fibronectin and neutrophil derived particles were visible within the fibronectin(+) ECM. Stromal cells appeared at day 5 after injury or later and collagen type I birefringent fibrils could be identified during the second week after injury. Our study suggests that neutrophils contribute to bone regeneration by synthesizing an "emergency ECM" before stromal cells infiltrate the FH and synthesize the eventual bone tissue. PMID- 26854618 TI - HEI-OC1 cells as a model for investigating prestin function. AB - The House Ear Institute-Organ of Corti 1 (HEI-OC1) is a mouse auditory cell line that endogenously express, among other several markers of cochlear hair cells, the motor protein prestin (SLC26A5). Since its discovery fifteen years ago, and because of the difficulties associated with working with outer hair cells, prestin studies have been performed mostly by expressing it exogenously in non specific systems such as HEK293 and TSA201, embryonic kidney cells from human origin, or Chinese Hamster Ovary (CHO) cells. Here, we report flow cytometry and confocal laser scanning microscopy studies on the pattern of prestin expression, as well as nonlinear capacitance (NLC) and whole cell-patch clamping studies on prestin motor function, in HEI-OC1 cells cultured at permissive and non permissive conditions. Our results indicate that both total prestin expression and plasma membrane localization increase in a time-dependent manner when HEI-OC1 cells differentiate under non-permissive culture conditions. In addition, we demonstrate that HEI-OC1 cells have a robust NLC associated to prestin motor function, which decreases when the density of prestin molecules present at the plasma membrane increases. Altogether, our results show that the response of endogenously expressed prestin in HEI-OC1 cells is different from the response of prestin expressed exogenously in non-auditory cells, and suggest that the HEI-OC1 cell line may be an important additional tool for investigating prestin function. PMID- 26854619 TI - Virulence profile: Laura Manuelidis. PMID- 26854620 TI - Determination of NLRP3 (rs4612666) and IL-1B (rs1143634) genetic polymorphisms in periodontally diseased and healthy subjects. AB - OBJECTIVE: The focus of the current study was to identify if a possible association between NLRP3 (rs4612666) and IL-1B (rs1143634) single-nucleotide polymorphisms (SNPs) may be implicated in the etiopathogenesis of chronic periodontitis (CP) in a Colombian population. DESIGN: One hundred and twenty-four CP subjects and 81 periodontally healthy controls (HC) were recruited. Periodontal status was assessed by criteria based on probing depth, clinical attachment level, extent, and severity of periodontal breakdown. Human genomic DNA was obtained from saliva samples of the study subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to identify the NLRP3 (rs4612666) and IL-1B (rs1143634) SNPs. The association of polymorphisms with CP was assessed individually and adjusted for confounding using a multivariate binary logistic regression model. RESULTS: Bivariate analysis showed a weak association between CT genotype of NLRP3 (rs4612666) SNP and CP, however after logistic regression analysis, neither NLRP3 (rs4612666) nor IL-1B (rs1143634) polymorphisms were strongly/independently associated with disease status. Even so, an interaction effect was significantly detected not only among CT/CC genotypes of NLRP3 gene regarding to the age stratum >= 48 years, but also between CC genotype of the same gene and smoking habit. CONCLUSION: Although the present results do not support that IL-1B (rs1143634) SNP could be identified as a risk predictor for CP in the present population, the synergistic interaction of the CT/CC genotypes of NLRP3 (rs4612666) SNP with ageing and/or smoking habit potentially might play a significant role in the pathogenic pathways of periodontal disease. PMID- 26854621 TI - Histopathological features of bisphosphonates related osteonecrosis of the jaw in rats with and without vitamin d supplementation. AB - OBJECTIVE: Aim of this study was to investigate the effect of vitamin-D3 on the osteonecrosis of bone that was induced after tooth extraction was conducted on rats that were given zoledronic acid (Z.A). MATERIAL AND METHODS: Animals were divided into four groups. Two of the experimental groups were divided into two subgroups, third study group was not divided into subgroups, and control group was divided into three subgroups. Z.A was administered twice per week over the course of 7 weeks, dexamethasone was administered twice a week during the 5th-6th 7th weeks to all groups. Dental extraction was performed by drilling around the tooth at 7th week. In study-group-1; vitamin-D was administered twice per week during the 5th-6th-7th weeks. In study-group 2; vitamin-D was administered twice per week during the 8th-9th-10th weeks. In study-group-3; vitamin-D was administered twice per week during the 15th-16th-17th weeks. The animals were sacrificed at 10th-15th-17th weeks, and histologic samples were taken. RESULTS: Postoperative-15-group had a lower osteoblast number, which was statistically significant as compared to preoperative-15 and control-15-group. Control-10-group showed significantly lower osteoclast number in comparison to preoperative-10 and postoperative-10-group. Osteoclast number was significantly higher in the osteonecrosis-17-group as compared to control-17-group. Preoperative-10-group showed significantly higher inflammation in comparison to control-10-group. Postoperative-15-group had a lower histologic osteonecrosis, which was statistically significant as compared to the control-15-group. Macroscopic osteonecrosis was significantly higher in the control-17-group in comparison to the osteonecrosis-17-group. CONCLUSIONS: We concluded that there are some proofs for the treatment of BRONJ with systemic using of vitamin-D. PMID- 26854622 TI - Effect of corruption on healthcare satisfaction in post-soviet nations: A cross country instrumental variable analysis of twelve countries. AB - There is the lack of consensus about the effect of corruption on healthcare satisfaction in transitional countries. Interpreting the burgeoning literature on this topic has proven difficult due to reverse causality and omitted variable bias. In this study, the effect of corruption on healthcare satisfaction is investigated in a set of 12 Post-Socialist countries using instrumental variable regression on the sample of 2010 Life in Transition survey (N = 8655). The results indicate that experiencing corruption significantly reduces healthcare satisfaction. PMID- 26854623 TI - Violence against children in humanitarian settings: A literature review of population-based approaches. AB - Children in humanitarian settings are thought to experience increased exposure to violence, which can impair their physical, emotional, and social development. Violence against children has important economic and social consequences for nations as a whole. The purpose of this review is to examine population-based approaches measuring violence against children in humanitarian settings. The authors reviewed prevalence studies of violence against children in humanitarian contexts appearing in peer-reviewed journals within the past twenty years. A Boolean search procedure was conducted in October 2014 of the electronic databases PubMed/Medline and PsychInfo. If abstracts contained evidence of the study's four primary themes--violence, children, humanitarian contexts and population-based measurement--a full document review was undertaken to confirm relevance. Out of 2634 identified articles, 22 met the final inclusion criteria. Across studies, there was varying quality and no standardization in measurement approach. Nine out of 22 studies demonstrated a relationship between conflict exposure and adverse health or mental health outcomes. Among studies that compared rates of violence between boys and girls, boys reported higher rates of physical violence, while girls reported higher rates of sexual violence. Children in infancy and early childhood were found to be among the most under-researched. Ultimately, the body of evidence in this review offers an incomplete picture regarding the prevalence, nature and impact of violence against children in emergencies, demonstrating a weak evidence base for some of the basic assumptions underpinning humanitarian practice. The development of standardized approaches to more rigorously measure violence against children is urgently needed in order to understand trends of violence against children in humanitarian contexts, and to promote children's healthy development and well-being. PMID- 26854624 TI - Scarcity discourses and their impacts on renal care policy, practices, and everyday experiences in rural British Columbia. AB - Drawing from a qualitative case study in rural British Columbia, Canada, this paper examines the discourse of kidney scarcity and its impact on renal care policies and practices. Our findings suggest that at different levels of care, there are different discourses and treatment foci. We have identified three distinct scarcity discourses at work. At the macro policy level, the scarcity of transplantable kidneys is the dominant discourse. At the meso health care institution level, we witnessed a discourse regarding the scarcity of health care and human resources. At the micro community level, there was a discourse of the scarcity of health and life-sustaining resources. For each form of scarcity, particular responses are encouraged. At the macro level, renal care and transplant organizations emphasize the benefits of kidney transplantation and procuring more donors. At the meso level, participants from the regional health care system increasingly encourage home hemodialysis and patient-led care. At the micro level, community health care professionals push for rural renal patients to attend dialysis and maintain their care plans. This work contributes to critical, interdisciplinary organ transfer discourse by contextualizing kidney scarcity. It reveals the tension between these discourses and the implications of pursuing kidney donations without addressing the conditions in which individuals experience kidney failure. PMID- 26854626 TI - The impact of caring for grandchildren on the health of grandparents in Europe: A lifecourse approach. AB - Grandparents are becoming an increasingly important source of childcare. However, caring for grandchildren may have negative health consequences particularly for grandparents with intensive commitments such as those with primary care responsibilities. To date most studies on this issue are based on cross-sectional data and do not take earlier life circumstances into account. Thus, it is not known whether (or to what extent) the relationship between grandparental childcare and health is due to cumulative advantage or disadvantage throughout the lifecourse or to the impact of grandchild care per se. Employing data from waves 1-3 of the Survey of Health, Ageing and Retirement in Europe we investigated the longitudinal relationship between grandparental childcare (i.e. intensive and non-intensive) and health once cumulative histories of advantage or disadvantage are taken into account. We used latent class analysis to categorise respondents according to childhood socio-economic and health conditions drawing on life history information. Experiences in adulthood (e.g. periods of ill health) were also captured. We created a latent continuous physical health variable based on self- and observer-measured indicators. OLS regression was used to explore the association between physical health at wave 2 and grandparental childcare at baseline, controlling for conditions in childhood and adulthood, and for health and socio-economic characteristics. We found a positive longitudinal association between grandchild care and health even after earlier life health and socio-economic conditions were taken into account. However, this significant association was found only for grandmothers, and not grandfathers. Our results suggesting the health benefits of grandchild care are important given the widespread provision of grandparental childcare in Europe. However, further research on underlying mechanisms and causal pathways between grandchild care and grandparent health, as well as on gender differences in the pattern of association, is needed. PMID- 26854625 TI - Life course SES and cardiovascular risk: Heterogeneity across race/ethnicity and gender. AB - We examine four life course models as they relate to adolescent SES, adult SES, and cardiovascular risk--the sensitive period, pathways, accumulation, and social mobility models. Accounting for race/ethnic and gender differences in life course processes, we analyzed Waves I and IV of the National Longitudinal Study of Adolescent to Adult Health, a nationally representative sample of individuals enrolled in grades 7-12 when they were first interviewed in 1994/5. We restricted our sample to whites, blacks, and Latinos who were interviewed in Waves I and IV and provided biomarker data (n = 11,397). The cardiovascular risk score at Wave IV combined waist circumference, blood pressure, hemoglobin A1c, and C-reactive protein. We found evidence for each of the four life course models for white women, whereas the sensitive period was indicated for white men. Upward mobility was also associated with higher CVD risk among white men as compared to those who were socio-economically advantaged at both time points. The pathway model was significant for Latino women. No life course models were significant for black men or women or Latino men. Our findings demonstrate the importance of applying an intersectional lens to understanding CVD risk over the life course. PMID- 26854627 TI - The relative importance of health, income and social relations for subjective well-being: An integrative analysis. AB - There is much evidence that health, income and social relationships are important for our well-being, but little evidence on their relative importance. This study makes an integrative analysis of the relative influence of health related quality of life (HRQoL), household income and social relationships for subjective well being (SWB), where SWB is measured by the first three of the five items on the satisfaction with life scale (SWLS). In a comprehensive 2012 survey from six countries, seven disease groups and representative healthy samples (N = 7933) reported their health along several measures of HRQoL. A Shapley value decomposition method measures the relative importance of health, income and social relationships, while a quantile regression model tests how the effects of each of the three predictors vary across different points of SWB distributions. Results are compared with the standard regression. The respective marginal contribution of social relationships, health and income to SWB (as a share of goodness-of-fit) is 50.2, 19.3 and 7.3% when EQ-5D-5L is used as a measure of health. These findings are consistent across models based on five alternative measures of HRQoL. The influence of the key determinants varied significantly between low and high levels of the SWB distribution, with health and income having stronger influence among those with relatively lower SWB. Consistent with several studies, income has a significantly positive association with SWB, but with diminishing importance. PMID- 26854628 TI - Endophilin A2 protects H2O2-induced apoptosis by blockade of Bax translocation in rat basilar artery smooth muscle cells. AB - BACKGROUND: Apoptosis plays a central role in maintaining the normal cell number and tissue homeostasis. Endophilins are a family of evolutionarily conserved proteins that have the critical role in endocytosis. Here, we determined whether endophilin A2 (EndoII) contributes to hydrogen peroxide (H2O2)-induced apoptosis in rat basilar artery smooth muscle cells (BASMCs) and the underlying mechanisms. METHODS AND RESULTS: By using small interference RNA (siRNA) and EndoII overexpression strategy, we found that EndoII siRNA knockdown reduced cell viability and promoted H2O2-induced cell apoptosis, evidenced by loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-9, 3 and poly (ADP-ribose) polymerase (PARP). In contrast, EndoII overexpression showed opposite effects and inhibited H2O2-induced BASMCs apoptosis. Further studies revealed that there was a direct interaction between EndoII and Bax. Upon H2O2-induced apoptosis, the association of EndoII with Bax were significantly decreased, while the interaction of Bax/tBid were increased, accompanied by a translocation of Bax from cytosol to mitochondria. Knockdown of EndoII did not affect the expression of Bax, but further promoted the binding of Bax with tBid and favored the accumulation of Bax to mitochondria as well as Bax activation; whereas EndoII overexpression produced the opposite effects. In addition, EndoII siRNA aggravated, but EndoII overexpression alleviated, the reduction of Bcl-2 expression in H2O2-treated cells. CONCLUSIONS: These data suggested a role of EndoII in protecting BASMCs apoptosis induced by H2O2, possibly by inhibiting the addressing of Bax to mitochondria. Targeting on EndoII may be a new strategy to treat apoptosis-associated diseases. PMID- 26854630 TI - Could Good Care Mean Withholding Information from Patients? PMID- 26854631 TI - What's the Role of Autonomy in Patient- and Family-Centered Care When Patients and Family Members Don't Agree? PMID- 26854629 TI - ATP sensitive K(+) channels are critical for maintaining myocardial perfusion and high energy phosphates in the failing heart. AB - Congestive heart failure (CHF) is associated with intrinsic alterations of mitochondrial oxidative phosphorylation which lead to increased myocardial cytosolic free ADP. ATP sensitive K(+) channels (KATP) act as metabolic sensors that are important for maintaining coronary blood flow (MBF) and in mediating the response of the myocardium to stress. Coronary adenosine receptors (AdR) are not normally active but cause vasodilation during myocardial ischemia. This study examined the myocardial energetic response to inhibition of KATP and AdR in CHF. CHF (as evidenced by LVEDP>20mmHg) was produced in adult mongrel dogs (n=12) by rapid ventricular pacing for 4weeks. MBF was measured with radiolabeled microspheres during baseline (BL), AdR blockade with 8-phenyltheophylline (8-PT; 5mg/kg iv), and KATP blockade with glibenclamide (GLB; 20MUg/kg/min ic). High energy phosphates were examined with (31)P magnetic resonance spectroscopy (MRS) while myocardial oxygenation was assessed from the deoxymyoglobin signal (Mb delta) using (1)H MRS. During basal conditions the phosphocreatine (PCr)/ATP ratio (1.73+/-0.15) was significantly lower than in previously studied normal dogs (2.42+/-0.11) although Mb-delta was undetectable. 8-PT caused ~21% increase in MBF with no change in PCr/ATP. GLB caused a 33+/-0.1% decrease in MBF with a decrease in PCr/ATP from 1.65+/-0.17 to 1.11+/-0.11 (p<0.0001). GLB did not change the pseudo-first-order rate constant of ATP production via CK (kf), but the ATP production rate via CK was reduced by 35+/-0.08%; this was accompanied by an increase in Pi/PCr and appearance of a Mb-delta signal indicating tissue hypoxia. Thus, in the failing heart the balance between myocardial ATP demands and oxygen delivery is critically dependent on functioning KATP channels. PMID- 26854632 TI - Should Children be Asked to be Bone Marrow Donors for Siblings? PMID- 26854633 TI - Teaching Patient- and Family-Centered Care: Integrating Shared Humanity into Medical Education Curricula. PMID- 26854634 TI - Creating Value with the Patient- and Family-Centered Care Methodology and Practice: What Trainees Need to Know, Why, and Strategies for Medical Education. PMID- 26854635 TI - Patient- and Family-Centered Care: It's Not Just for Pediatrics Anymore. PMID- 26854636 TI - Patient- and Family-Centered Care: A Systematic Approach to Better Ethics and Care. PMID- 26854637 TI - Moving Past Individual and "Pure" Autonomy: The Rise of Family-Centered Patient Care. PMID- 26854638 TI - We Got Your Back: Patient Advocacy Through Art. PMID- 26854639 TI - Taking Our Oath Seriously: Compassion for Patients. PMID- 26854640 TI - Evidence-Based Design: Structuring Patient- and Family-Centered ICU Care. PMID- 26854641 TI - Physician Health Programs and the Social Contract. PMID- 26854642 TI - Synthetic Prions Provide Clues for Understanding Prion Diseases. AB - This Commentary highlights the article by Makarava et al that discusses the formation of synthetic prions and the role of substrate levels in their evolution. PMID- 26854644 TI - Trimeric cluster of lithium amidoborane-the smallest unit for the modeling of hydrogen release mechanism. AB - A detailed first-principle DFT M06/6-311++G(d.p) study of dehydrogenation mechanism of trimeric cluster of lithium amidoborane is presented. The first step of the reaction is association of two LiNH2 BH3 molecules in the cluster. The dominant feature of the subsequent reaction pathway is activation of H atom of BH3 group by three Li atoms with formation of unique Li3 H moiety. This Li3 H moiety is destroyed prior to dehydrogenation in favor of formation of a triangular Li2 H moiety, which interacts with protic H atom of NH2 group. As a result of this interaction, Li2 H2 moiety is produced. It features N(-) ?H(+) ?H( ) group suited near the middle plane between two Li(+) in the transition state that leads to H2 release. The transition states of association and hydrogen release steps are similar in energy. It is concluded that the trimer, (LiNH2 BH3 )3 , is the smallest cluster that captures the essence of the hydrogen release reaction. PMID- 26854643 TI - Synthesis and Biological Evaluation of 1,2,3-triazole tethered Pyrazoline and Chalcone Derivatives. AB - A series of pyrazoline derivatives and corresponding chalcone intermediates with substituents same as combretastatin-A4(CA-4) conjugated with triazole nucleus has been synthesized and evaluated for their anticancer potential. Sulphorhodamine B(SRB) assay indicated compound 12c to be the most active compound from the series with GI50 value of 6.7 MUm against the human liver carcinoma cell line HepG2. Interestingly, the intermediate 11c exhibited more promising cytotoxicity demonstrating GI50 value of 1.3 MUm against the prostate cancer cell line DU145. Compounds 11c and 12c caused accumulation of cells in G2/M phase and inhibited tubulin polymerization. Furthermore, these compounds reduce the mitochondrial membrane potential and activate caspases 3 and 9, thereby indicating their ability to trigger apoptosis. PMID- 26854645 TI - Protective antifungal activity of essential oils extracted from Buddleja perfoliata and Pelargonium graveolens against fungi isolated from stored grains. AB - AIMS: The chemical composition and antifungal activity of essential oils extracted from Buddleja perfoliata and Pelargonium graveolens were analysed to assess their efficacy as a potential alternative to synthetic chemical fungicides to protect stored grain. METHODS AND RESULTS: Essential oils were obtained by hydrodistillation, while GC-MS were used to characterize the components of theses oils. The main components identified from the essential oil of B. perfoliata were cubenol, eudesmol, germacrene D-4-ol and cis-verbenol; whereas (-)-aristolene, beta-citronellol and geraniol, were identified in P. graveolens. These essential oils were tested against a panel of fungal strains isolated from stored grains. Toxicity of the essential oils was assessed using two models represented by human derived macrophages and the brine shrimp assay. Moreover, inflammatory response of the oils was assessed by measuring secretion of the pro-inflammatory cytokines IL-6 and TNF-alpha using a human-derived macrophage cell line. Results show potent antifungal activity against a collection of fungi, with minimal inhibitory concentrations ranging from 0.3 to 50 MUg ml(-1) for both plants. A moderated cytotoxicity was observed, but no inflammatory responses. CONCLUSIONS: These oils can be used as an alternative for synthetic chemical fungicides used to protect stored grains. SIGNIFICANCE AND IMPACT OF THE STUDY: Synthetic chemical fungicides are used to protect stored grains, but their broad use raises concerns about effects on the environment and human health. The impact of the present report is that the use of essential oils is an eco-friendly alternative for fungal control in postharvest grains with a low impact to the environment. PMID- 26854646 TI - Does altered aortic flow in marfan syndrome relate to aortic root dilatation? AB - PURPOSE: To examine possible hemodynamic alterations in adolescent to adult Marfan syndrome (MFS) patients with aortic root dilatation. MATERIALS AND METHODS: Four-dimensional flow MRI was performed in 20 MFS patients and 12 age matched normal subjects with a 3T system. The cross-sectional areas of 10 planes along the aorta were segmented for calculating the axial and circumferential wall shear stress (WSSaxial , WSScirc ), oscillatory shear index (OSIaxial , OSIcirc ), and the nonroundness (NR), presenting the asymmetry of segmental WSS. Pearson's correlation analysis was performed to present the correlations between the quantified indices and the body surface area (BSA), aortic root diameter (ARD), and Z score of the ARD. P < 0.05 indicated statistical significance. RESULTS: Patients exhibited lower WSSaxial in the aortic root and the WSScirc in the arch (P < 0.05-0.001). MFS patients exhibited higher OSIaxial and OSIcirc in the sinotubular junction and arch, but lower OSIcirc in the descending aorta (all P < 0.05). The NR values were lower in patients (P < 0.05). The WSSaxial or WSScirc exhibited moderate to strong correlations with BSA, ARD, or Z score (R(2) = 0.50-0.72) in MFS patients. CONCLUSION: The significant differences in the quantified indices, which were associated with BSA, ARD, or Z score, in MFS were opposite to previous reports for younger MFS patients, indicating that altered flows in MFS patients may depend on the disease progress. The possible time dependency of hemodynamic alterations in MFS patients strongly suggests that longitudinal follow-up of 4D Flow is needed to comprehend disease progress. J. Magn. Reson. Imaging 2016;44:500-508. PMID- 26854647 TI - Pre-transplant phospholipase A2 receptor autoantibody concentration is associated with clinically significant recurrence of membranous nephropathy post-kidney transplantation. AB - Previous studies that have assessed the association of pre-transplant antiphospholipase A2 receptor autoantibody (PLA2R-Ab) concentration with a recurrence of membranous nephropathy (rMN) post-kidney transplant have yielded variable results. We tested 16 consecutive transplant patients with a history of iMN for pre-transplant PLA2R-Ab. Enzyme-linked immunosorbent assay titers (Euroimmun, NJ, USA) >14 RU/mL were considered positive. A receiver operating characteristic (ROC) analysis was performed after combining data from Quintana et al. (n = 21; Transplantation February 2015) to determine a PLA2R-Ab concentration which could predict rMN. Six of 16 (37%) patients had biopsy-proven rMN at a median of 3.2 yr post-transplant. Of these, five of six (83%) had a positive PLA2R-Ab pre-transplant with a median of 82 RU/mL (range = 31-1500). The only patient who had rMN with negative PLA2R-Ab was later diagnosed with B-cell lymphoma. One hundred percent (n = 10) of patients with no evidence of rMN (median follow-up = five yr) had negative pre-transplant PLA2R-Ab. In a combined ROC analysis (n = 37), a pre-transplant PLA2R-Ab > 29 RU/mL predicted rMN with a sensitivity of 85% and a specificity of 92%. Pre-transplant PLA2R-Ab could be a useful tool for the prediction of rMN. Patients with rMN in the absence of PLA2R Ab should be screened for occult malignancy and/or alternate antigens. PMID- 26854648 TI - Low-target tacrolimus in de novo standard risk renal transplant recipients: A single-centre experience. AB - AIM: Optimal tacrolimus exposure in transplant recipients is not well established. The results from the Symphony study indicated that low-target tacrolimus (trough concentrations 3-7 ug/L) in de novo standard risk renal transplant recipients should be appropriate. The aim of this study was to evaluate real-life outcomes when applying a similar strategy in a clinical setting. METHODS: A single-centre analysis was conducted in standard risk renal transplant recipients receiving low-target tacrolimus, mycophenolate mofetil, glucocorticoids and basiliximab induction. One-year estimated glomerular filtration rate (eGFR, Cockcroft-Gault), one-year biopsy-proven acute rejection rate and graft- and patient survival up to 3 years post-transplant were compared with the outcomes in the Symphony study. RESULTS: From 1 January 2009 to 31 March 2013, we included 406 patients. One year after transplantation, the mean +/- SD eGFR was 76.8 +/- 28.3 mL/min (Symphony: 65.4 +/- 27.0 mL/min, P < 0.001). Biopsy proven acute rejections were seen in 14.5% of the patients (Symphony: 12.3%, P = 0.35). Kaplan-Meier estimates [95% confidence interval] of three-year death censored graft- and patient survival were 96.6% [94.2-99.0%] (Symphony: 93%) and 95.0% [92.6-97.3%] (Symphony: 95%), respectively. CONCLUSION: Low-target tacrolimus-based immunosuppression is safe and effective also in a standard clinical setting in de novo standard risk renal transplant recipients. PMID- 26854650 TI - Temperature Effect on Micelle Formation: Molecular Thermodynamic Model Revisited. AB - Temperature affects the aggregation of macromolecules such as surfactants, polymers, and proteins in aqueous solutions. The effect on the critical micelle concentration (CMC) is often nonmonotonic. In this work, the effect of temperature on the micellization of ionic and nonionic surfactants in aqueous solutions is studied using a molecular thermodynamic model. Previous studies based on this technique have predicted monotonic behavior for ionic surfactants. Our investigation shows that the choice of tail transfer energy to describe the hydrophobic effect between the surfactant tails and the polar solvent molecules plays a key role in the predicted CMC. We modify the tail transfer energy by taking into account the effect of the surfactant head on the neighboring methylene group. The modification improves the description of the CMC and the predicted micellar size for aqueous solutions of sodium n-alkyl sulfate, dodecyl trimethylammonium bromide (DTAB), and n-alkyl polyoxyethylene. The new tail transfer energy describes the nonmonotonic behavior of CMC versus temperature. In the DTAB-water system, we redefine the head size by including the methylene group, next to the nitrogen, in the head. The change in the head size along with our modified tail transfer energy improves the CMC and aggregation size prediction significantly. Tail transfer is a dominant energy contribution in micellar and microemulsion systems. It also promotes the adsorption of surfactants at fluid-fluid interfaces and affects the formation of adsorbed layer at fluid-solid interfaces. Our proposed modifications have direct applications in the thermodynamic modeling of the effect of temperature on molecular aggregation, both in the bulk and at the interfaces. PMID- 26854649 TI - Squamous cell cancer of the nasal cavity: New insights and implications for diagnosis and treatment. AB - BACKGROUND: Squamous cell carcinoma (SCC) of the nasal cavity is a rare malignancy and often analyzed in heterogeneous studies with other tumors of the nose or the paranasal sinuses. The purpose of this study was to evaluate distinct risk factors, tumor characteristics, outcome predictors, and the prevalence of human papillomavirus (HPV) in SCC of the nasal cavity. METHODS: We conducted a retrospective study of 39 patients treated at a single quaternary medical care and cancer center. We analyzed tumor characteristics, HPV status, treatment, and outcome. We present the largest study on SCC of the nasal cavity from a single center. RESULTS: The majority of patients (70.2%) presented with an early-stage tumor (T1 or T2). Only 1 patient had a single neck metastasis at the time of diagnosis. Four tumors were HPV-positive. Most patients (61.5%) underwent surgical resection without adjuvant treatment, with 12 patients (30.8%) undergoing additional radiotherapy. Three patients were treated with primary radiotherapy or chemoradiotherapy. No patient treated primarily with total rhinectomy developed local tumor recurrence. CONCLUSION: Local tumor control is crucial, even if it makes radical surgery necessary. Postoperative epithetic treatment enables reliable follow-up examinations. Regional metastases at the time of diagnosis are rare. Neck dissection should therefore be reserved for cases of suspected metastasis. HPV may also play a role in the etiology of SCC of the nasal cavity. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2112-E2117, 2016. PMID- 26854651 TI - Treatment related outcomes in high-risk endometrial carcinoma: Canadian high risk endometrial cancer consortium (CHREC). AB - OBJECTIVE: The lack of randomized clinical data pertaining to optimal surgery and adjuvant treatment in women with high-risk histotypes of endometrial cancer has resulted in selective management based on institutional policies. The objective of this study was to assess differences in treatment strategies and their outcomes among various institutions. METHOD: High-risk endometrial cancer cases (2000-2012) with corresponding clinicopathologic data were collected from 7 academic cancer centers. Histotypes included grade 3 endometrioid (EC3), serous (ESC), clear cell (CCC) and carcinosarcoma (CS). Associations with overall survival were performed using Cox proportional hazard regression. RESULTS: 1260 patients treated between 2000 and 2012 were included in the study: 398 EC3, 449 ESC, 91 CCC, 236 CS and 83 'other'. The use of adjuvant chemotherapy, adjuvant radiation, and extent of surgical staging were statistically different among the 7 centers (P<0.001). Histotype was independently associated with overall survival (OS) in patients with stage 1 and 2 disease who underwent surgical staging (P=0.0324). Adjuvant radiation was associated with improved OS for EC3 and CCC and adjuvant chemotherapy was associated with improved OS for ESC and CS. There was a high rate of recurrence (17.8% and 21.4%) in completely staged, stage 1A patients with ESC and CS respectively. CONCLUSION: There exists a wide variation in practice and outcomes for high-risk histotypes of endometrial cancer. The relative impact of adjuvant therapy appears to be histotype dependent and prospective studies examining adjuvant treatment in high-risk histotypes should use caution combining them together. PMID- 26854653 TI - Use of Time-Resolved Fluorescence To Improve Sensitivity and Dynamic Range of Gel Based Proteomics. AB - Limitations in the sensitivity and dynamic range of two-dimensional gel electrophoresis (2-DE) are currently hampering its utility in global proteomics and biomarker discovery applications. In the current study, we present proof-of concept analyses showing that introducing time-resolved fluorescence in the image acquisition step of in-gel protein quantification provides a sensitive and accurate method for subtracting confounding background fluorescence at the photon level. In-gel protein detection using the minimal difference gel electrophoresis workflow showed improvements in lowest limit of quantification in terms of CyDye molecules per pixel of 330-fold in the blue-green region (Cy2) and 8000-fold in the red region (Cy5) over conventional state-of-the-art image acquisition instrumentation, here represented by the Typhoon 9400 instrument. These improvements make possible the detection of low-abundance proteins present at sub attomolar levels, thereby representing a quantum leap for the use of gel-based proteomics in biomarker discovery. These improvements were achieved using significantly lower laser powers and overall excitation times, thereby drastically decreasing photobleaching during repeated scanning. The single fluorochrome detection limits achieved by the cumulative time-resolved emission two-dimensional electrophoresis (CuTEDGE) technology facilitates in-depth proteomics characterization of very scarce samples, for example, primary human tissue materials collected in clinical studies. The unique information provided by high-sensitivity 2-DE, including positional shifts due to post-translational modifications, may increase the chance to detect biomarker signatures of relevance for identification of disease subphenotypes. PMID- 26854652 TI - Nitrone Cycloadditions of 1,2-Cyclohexadiene. AB - We report the first 1,3-dipolar cycloadditions of 1,2-cyclohexadiene, a rarely exploited strained allene. 1,2-Cyclohexadiene is generated in situ under mild conditions and trapped with nitrones to give isoxazolidine products in synthetically useful yields. The reactions occur regioselectively and exhibit a notable endo preference, thus resulting in the controlled formation of two new bonds and two stereogenic centers. DFT calculations of stepwise and concerted reaction pathways are used to rationalize the observed selectivities. Moreover, the strategic manipulation of nitrone cycloadducts demonstrates the utility of this methodology for the assembly of compounds bearing multiple heterocyclic units. These studies showcase the exploitation of a traditionally avoided reactive intermediate in chemical synthesis. PMID- 26854654 TI - Spontaneous Extrahepatic Portosystemic Shunt in Congenital Hepatic Fibrosis. PMID- 26854655 TI - Ustekinumab in Pediatric Crohn Disease Patients. AB - OBJECTIVES: We describe the use of ustekinumab for 4 patients with pediatric Crohn disease treated at the Seattle Children's Hospital Inflammatory Bowel Disease Center. METHODS: A retrospective chart review was done to identify patients' clinical data, disease phenotype, treatment history, and laboratory and growth parameters before treatment with ustekinumab and at last follow-up. Adverse events while on ustekinumab were also recorded. RESULTS: Four adolescent patients with Crohn disease at our center received ustekinumab. All had previously received corticosteroids, methotrexate, azathioprine/6-mercaptopurine, and both infliximab and adalimumab. Patients had varying disease phenotypes. Ages at ustekinumab initiation were 12, 13, 16, and 17 years. Weight ranged from 40.5 to 57.8 kg, mean 49.5 kg. Two patients showed clinical response and remain on ustekinumab. Two patients discontinued therapy because of continued symptoms and disease complications and required multiple hospitalizations. CONCLUSIONS: Ustekinumab was used in 4 children with pediatric Crohn disease with 2 of 4 patients showing clinical response (1 with persistently elevated C-reactive protein). A prospective study is needed to define its efficacy, safety, and placement in managing pediatric Crohn disease in the future. PMID- 26854656 TI - Surgical Management of Spinal Chondrosarcomas. AB - STUDY DESIGN: An ambispective cohort study. OBJECTIVE: The aim of this study was to determine whether the application of the Enneking classification in the management of spinal chondrosarcomas influences local recurrence and survival. SUMMARY OF BACKGROUND DATA: Primary spinal chondrosarcomas are rare. Best available evidence is based on small case series, thus making it difficult to determine optimal management and risk factors for local recurrence and survival. METHODS: The AOSpine Knowledge Forum Tumor developed a multicenter ambispective database of surgically treated patients with spinal chondrosarcoma. Patient data pertaining to demographics, diagnosis, treatment, cross-sectional survival, and local recurrence were collected. Tumors were classified according to the Enneking classification. Patients were divided into two cohorts: Enneking appropriate (EA) and Enneking inappropriate (EI). They were categorized as EA when the final pathological assessment of the margin matched the Enneking recommendation, and otherwise, they were categorized as EI. RESULTS: Between 1987 and 2011, 111 patients (37 female; 74 male) received surgical treatment for a primary spinal chondrosarcoma at a mean age of 47.4 +/- 15.8 years. Patients were followed for a median period of 3.1 years (range = 203 d-18.7 yrs). Median survival for the entire cohort was 8.4 years postoperative. After 10 years postoperative, 36 (32%) patients died and 37 (35%) patients suffered a local recurrence. Twenty-three of these 37 patients who suffered a local recurrence died. Sixty (58%) patients received an EA procedure while 44 (42%) received an EI procedure. EI patients had a higher hazard ratio for local recurrence than those who received an EA procedure (P = 0.052). Local recurrence was strongly associated with chondrosarcoma-related death (risk ratio = 3.6, P < 0.010). CONCLUSION: This is the largest multicenter cohort of spinal chondrosarcomas. EA surgical management appeared to correlate with a decreased risk of local recurrence, yet no relationship with survival was found. Where possible, surgeons should strive to achieve EA margins to minimize the risk of local recurrence. LEVEL OF EVIDENCE: 4. PMID- 26854657 TI - To the Editor. PMID- 26854658 TI - To the Editor. PMID- 26854659 TI - Executive Summary. PMID- 26854660 TI - Foreword. PMID- 26854661 TI - Don't forget to ventilate during cardiopulmonary resuscitation with mechanical chest compression devices. PMID- 26854662 TI - Evolution of NADPH-cytochrome P450 oxidoreductases (POR) in Apiales - POR 1 is missing. AB - The NADPH-dependent cytochrome P450 oxidoreductase (POR) is the obligate electron donor to eukaryotic microsomal cytochromes P450 enzymes. The number of PORs within plant species is limited to one to four isoforms, with the most common being two PORs per plant. These enzymes provide electrons to a huge number of different cytochromes P450s (from 50 to several hundred within one plant). Within the eudicotyledons, PORs can be divided into two major clades, POR 1 and POR 2. Based on our own sequencing analysis and publicly available data, we have identified 45 PORs from the angiosperm order Apiales. These were subjected to a phylogenetic analysis along with 237 other publicly available (NCBI and oneKP) POR sequences found within the clade Asterids. Here, we show that the order Apiales only harbor members of the POR 2 clade, which are further divided into two distinct subclades. This is in contrast to most other eudicotyledon orders that have both POR 1 and POR 2. This suggests that through gene duplications and one gene deletion, Apiales only contain members of the POR 2 clade. Three POR 2 isoforms from Thapsia garganica L., Apiaceae, were all full-length in an Illumina root transcriptome dataset (available from the SRA at NCBI). All three genes were shown to be functional upon reconstitution into nanodiscs, confirming that none of the isoforms are pseudogenes. PMID- 26854663 TI - Domain-swap polymerization drives the self-assembly of the bacterial flagellar motor. AB - Large protein complexes assemble spontaneously, yet their subunits do not prematurely form unwanted aggregates. This paradox is epitomized in the bacterial flagellar motor, a sophisticated rotary motor and sensory switch consisting of hundreds of subunits. Here we demonstrate that Escherichia coli FliG, one of the earliest-assembling flagellar motor proteins, forms ordered ring structures via domain-swap polymerization, which in other proteins has been associated with uncontrolled and deleterious protein aggregation. Solution structural data, in combination with in vivo biochemical cross-linking experiments and evolutionary covariance analysis, revealed that FliG exists predominantly as a monomer in solution but only as domain-swapped polymers in assembled flagellar motors. We propose a general structural and thermodynamic model for self-assembly, in which a structural template controls assembly and shapes polymer formation into rings. PMID- 26854664 TI - A new MCM modification cycle regulates DNA replication initiation. AB - The MCM DNA helicase is a central regulatory target during genome replication. MCM is kept inactive during G1, and it initiates replication after being activated in S phase. During this transition, the only known chemical change to MCM is the gain of multisite phosphorylation that promotes cofactor recruitment. Because replication initiation is intimately linked to multiple biological cues, additional changes to MCM can provide further regulatory points. Here, we describe a yeast MCM SUMOylation cycle that regulates replication. MCM subunits undergo SUMOylation upon loading at origins in G1 before MCM phosphorylation. MCM SUMOylation levels then decline as MCM phosphorylation levels rise, thus suggesting an inhibitory role of MCM SUMOylation during replication. Indeed, increasing MCM SUMOylation impairs replication initiation, partly through promoting the recruitment of a phosphatase that decreases MCM phosphorylation and activation. We propose that MCM SUMOylation counterbalances kinase-based regulation, thus ensuring accurate control of replication initiation. PMID- 26854665 TI - Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation. AB - The CMG helicase is composed of Cdc45, Mcm2-7 and GINS. Here we report the structure of the Saccharomyces cerevisiae CMG, determined by cryo-EM at a resolution of 3.7-4.8 A. The structure reveals that GINS and Cdc45 scaffold the N tier of the helicase while enabling motion of the AAA+ C tier. CMG exists in two alternating conformations, compact and extended, thus suggesting that the helicase moves like an inchworm. The N-terminal regions of Mcm2-7, braced by Cdc45-GINS, form a rigid platform upon which the AAA+ C domains make longitudinal motions, nodding up and down like an oil-rig pumpjack attached to a stable platform. The Mcm ring is remodeled in CMG relative to the inactive Mcm2-7 double hexamer. The Mcm5 winged-helix domain is inserted into the central channel, thus blocking entry of double-stranded DNA and supporting a steric-exclusion DNA unwinding model. PMID- 26854666 TI - A transcription activator-like effector (TALE) induction system mediated by proteolysis. AB - Simple and predictable trans-acting regulatory tools are needed in the fields of synthetic biology and metabolic engineering to build complex genetic circuits and optimize the levels of native and heterologous gene products. Transcription activator-like effectors (TALEs) are bacterial virulence factors that have recently gained traction in biotechnology applications owing to their customizable DNA-binding specificity. In this work we expanded the versatility of these transcription factors to create an inducible TALE system by inserting tobacco-etch virus (TEV) protease recognition sites into the TALE backbone. The resulting engineered TALEs maintain transcriptional repression of their target genes in Escherichia coli, but are degraded after induction of the TEV protease, thereby promoting expression of the previously repressed target gene of interest. This TALE-TEV technology enables both repression and induction of plasmid or chromosomal target genes in a manner analogous to traditional repressor proteins but with the added flexibility of being operator-agnostic. PMID- 26854667 TI - A proactive role of water molecules in acceptor recognition by protein O fucosyltransferase 2. AB - Protein O-fucosyltransferase 2 (POFUT2) is an essential enzyme that fucosylates serine and threonine residues of folded thrombospondin type 1 repeats (TSRs). To date, the mechanism by which this enzyme recognizes very dissimilar TSRs has been unclear. By engineering a fusion protein, we report the crystal structure of Caenorhabditis elegans POFUT2 (CePOFUT2) in complex with GDP and human TSR1 that suggests an inverting mechanism for fucose transfer assisted by a catalytic base and shows that nearly half of the TSR1 is embraced by CePOFUT2. A small number of direct interactions and a large network of water molecules maintain the complex. Site-directed mutagenesis demonstrates that POFUT2 fucosylates threonine preferentially over serine and relies on folded TSRs containing the minimal consensus sequence C-X-X-S/T-C. Crystallographic and mutagenesis data, together with atomic-level simulations, uncover a binding mechanism by which POFUT2 promiscuously recognizes the structural fingerprint of poorly homologous TSRs through a dynamic network of water-mediated interactions. PMID- 26854669 TI - The Impact of Pharmacotherapy of Type 2 Diabetes Mellitus on IL-1beta, IL-6 and IL-10 Secretion. AB - BACKGROUND: The aim of this study was to assess the impact of pharmacotherapy of diabetes on atherosclerosis, as reflected in interleukin (IL)-1beta, IL-6 and IL 10 serum levels. METHODS: We studied patients with type 2 diabetes, treated with metformin, insulin combined with metformin and conventional insulin. IL-1beta, IL 6 and IL-10 serum levels were assayed using BDTM Cytometric Bead Array. Multivariate analysis of covariance was performed to exclude the impact of some metabolic and anthropometric factors on differences in cytokines concentrations among the participants receiving different pharmacotherapy. RESULTS: The serum concentrations of IL-1beta and IL-6 were significantly higher and IL-10 serum levels were significantly lower in the insulin-treated group than in other therapeutic groups. Covariance analysis confirmed that differences in IL-1beta and IL-6 levels were determined by pharmacotherapy and fasting plasma glucose, whereas in IL-10 levels by the therapy only. Additionally, peptide C modified differences in IL-1beta levels and HbA1c in IL-6 concentrations. CONCLUSION: This study revealed that both pharmacotherapy and glycemic control may modify some pro atherogenic factors, such as IL-1beta and IL-6. The therapy with metformin and insulin combined with metformin seems to be much more beneficial in terms of their impact on pro-inflammatory cytokines secretion in comparison to conventional insulinotherapy. PMID- 26854668 TI - Engineering nonphosphorylative metabolism to generate lignocellulose-derived products. AB - Conversion of lignocellulosic biomass into value-added products provides important environmental and economic benefits. Here we report the engineering of an unconventional metabolism for the production of tricarboxylic acid (TCA)-cycle derivatives from D-xylose, L-arabinose and D-galacturonate. We designed a growth based selection platform to identify several gene clusters functional in Escherichia coli that can perform this nonphosphorylative assimilation of sugars into the TCA cycle in less than six steps. To demonstrate the application of this new metabolic platform, we built artificial biosynthetic pathways to 1,4 butanediol (BDO) with a theoretical molar yield of 100%. By screening and engineering downstream pathway enzymes, 2-ketoacid decarboxylases and alcohol dehydrogenases, we constructed E. coli strains capable of producing BDO from D xylose, L-arabinose and D-galacturonate. The titers, rates and yields were higher than those previously reported using conventional pathways. This work demonstrates the potential of nonphosphorylative metabolism for biomanufacturing with improved biosynthetic efficiencies. PMID- 26854670 TI - Self-Healing and Moldable Metallogels as the Recyclable Materials for Selective Dye Adsorption and Separation. AB - Four multiresponsive and self-sustaining metallogels were synthesized by the reaction of the disodium salt of the ligand carboxymethyl-(3,5-di-tert-butyl-2 hydroxy-benzyl)amino acetic acid with Cd(II) and Zn(II) halides, which were found to show excellent selectivity for dye adsorption and separation, and one of the gels shows a rare self-healing property. PMID- 26854671 TI - Last year. PMID- 26854672 TI - Huge thrombus formation 1 year after percutaneous closure of an atrial septal defect with an Amplatzer septal occluder. PMID- 26854673 TI - Treatment of pulmonary hypertension in three patients with beta-thalassemia intermedia using pulmonary arterial hypertension-specific medications. PMID- 26854674 TI - Spontaneous pneumopericardium in a pregnant woman. PMID- 26854675 TI - Mercury overexposure and atrial fibrillation. PMID- 26854676 TI - Author's Reply. PMID- 26854677 TI - Nonthyroidal illness syndrome in off-pump coronary artery bypass surgery. PMID- 26854678 TI - Author's Reply. PMID- 26854679 TI - Renal dysfunction as a marker of increased mortality in patients with pulmonary thromboembolism. PMID- 26854680 TI - Author's Reply. PMID- 26854681 TI - Coronary slow flow: Benign or ominous? PMID- 26854682 TI - Author's Reply. PMID- 26854683 TI - In stent restenosis after percutaneous coronary intervention. PMID- 26854684 TI - Author's Reply. PMID- 26854685 TI - Frequency of emergencies in adults due to unrecognized coarctation of the aorta. PMID- 26854687 TI - Extended ellipse-line-ellipse trajectory for long-object cone-beam imaging with a mounted C-arm system. AB - Recent reports show that three-dimensional cone-beam (CB) imaging with a floor mounted (or ceiling-mounted) C-arm system has become a valuable tool in interventional radiology. Currently, a circular short scan is used for data acquisition, which inevitably yields CB artifacts and a short coverage in the direction of the patient table. To overcome these two limitations, a more sophisticated data acquisition geometry is needed. This geometry should be complete in terms of Tuy's condition and should allow continuous scanning, while being compatible with the mechanical constraints of mounted C-arm systems. Additionally, the geometry should allow accurate image reconstruction from truncated data. One way to ensure such a feature is to adopt a trajectory that provides full R-line coverage within the field-of-view (FOV). An R-line is any segment of line that connects two points on a source trajectory, and the R-line coverage is the set of points that belong to an R-line. In this work, we propose a novel geometry called the extended ellipse-line-ellipse (ELE) for long-object imaging with a mounted C-arm system. This trajectory is built from modules consisting of two elliptical arcs connected by a line. We demonstrate that the extended ELE can be configured in many ways so that full R-line coverage is guaranteed. Both tight and relaxed parametric settings are presented. All results are supported by extensive mathematical proofs provided in appendices. Our findings make the extended ELE trajectory attractive for axially-extended FOV imaging in interventional radiology. PMID- 26854686 TI - The safety of medical devices containing DEHP plasticized PVC or other plasticizers on neonates and other groups possibly at risk (2015 update). PMID- 26854688 TI - Correlation between zoledronic acid infusion and repeat vertebroplasty surgery in osteoporotic patients. AB - Objective The incidence of bone fractures rapidly increases as people age, mostly due to bone loss resulting from osteoporosis. The purpose of this study is to compare the rates of repeat vertebroplasty in osteoporotic patients treated with or without zoledronic acid (ZOL) infusion following initial vertebroplasty. Research design and methods We conducted a retrospective chart review of osteoporotic patients who underwent vertebroplasty from June 2009 to June 2012. Patients with existing vertebral fracture(s) were retrospectively divided into two groups according to whether or not they received zoledronic acid infusion after initial vertebroplasty. Zoledronic acid infusion was intravenously administered once a year for three consecutive years, as a single 5 mg dose in 100 mL solution infused over at least 15 minutes. The primary efficacy variable was the number of patients requiring repeat vertebroplasty procedures after the initial surgery due to subsequent vertebral fractures. The Cox proportional hazards model was used to compare the risk ratios of repeat vertebroplasty between these two groups. Results A total of 1646 patients, including 456 males and 1190 females (age range: 65-89 years), were enrolled. Compared to the 1595 patients who did not receive osteoporosis medication, the 51 patients treated with zoledronic acid infusion demonstrated a significantly lower rate of repeat vertebroplasty. In the ZOL-treated group, only 4% of the patients (2/51) required a second vertebroplasty, compared to 13% (206/1595) in the non-ZOL-treated group (p = 0.032). Conclusions The results indicate that osteoporotic patients who undergo vertebroplasty are significantly less likely to require reoperation if treated with zoledronic acid infusion. However, since the number of male patients in the ZOL-treated group was limited, and since Taiwan's National Health System program does not cover the cost of receiving zoledronic acid infusions for male patients, the conclusion seems to be less certain for male osteoporotic patients. PMID- 26854689 TI - Translation and cross-cultural adaptation of the PARmed-X for Pregnancy into Brazilian Portuguese. AB - We describe the translation and cross-cultural adaptation of the PARmed-X for Pregnancy for use in Brazilian Portuguese. The original instrument was developed in English for health screening prior to and guidelines for prenatal exercise. We followed the ten steps according to the Translation and Cultural Adaptation International Society for Pharmacoeconomics and Outcomes Research guidelines. Our template can be used by other health professionals for translation and verification of the original tool into their native language. PMID- 26854690 TI - Evaluation of 1100 couples with recurrent pregnancy loss using conventional cytogenetic, PGD, and PGS: hype or hope. AB - Recurrent pregnancy loss (RPL) is an important clinical problem, mostly resulting from chromosomal or genetic defects, while in 30-60% of cases, it is idiopathic. The aim of this study is to evaluate the frequency and types of chromosomal abnormalities, also pre-implantation genetic diagnosis (PGD) and pre-implantation genetic screening (PGS) outcomes among Iranian couples with RPL. This retrospective study was conducted on 1100 Iranian couples (2200 individuals) with RPL referred to Royan Institute between 2008 and 2014. Karyotyping had been performed using standard cytogenetic techniques. PGD results of RPL patients with abnormal karyotypes and PGS results of RPL patients with normal karyotypes were also analyzed. The frequency of chromosomal abnormalities in these patients was 4.95%. Women demonstrated more abnormalities (6.82%) in comparison to men (3.09%). The successful rate of pregnancy after PGD and PGS was 52 and 18.64%, respectively. The observation of 4.95% chromosomal abnormalities among the patients with RPL could support this hypothesis that there is a direct relationship between chromosomal abnormalities and RPL. More than half of the patients who underwent PGD had successful pregnancy; therefore, this approach can improve the success rate of pregnancy in them. The results of PGS cycles showed that this technique could increase the live birth rate in RPL patients. PMID- 26854691 TI - Left-Sided Cardiac Valve Calcification: Another Rubik's Cube Puzzle. PMID- 26854692 TI - Tuberous sclerosis complex as a model disease for developing new therapeutics for epilepsy. AB - An unmet need in the treatment of epilepsy has been targeted therapies that prevent the onset or progression of seizures in the susceptible individual. We have no treatments that target the process of epileptogenesis, through which the genetically predisposed or injured brain becomes capable of generating unprovoked, recurrent seizures. Tuberous Sclerosis Complex (TSC) is a multiorgan disorder caused by a defect in the mTOR (mechanistic/mammalian target of rapamycin) pathway. Epilepsy is a prominent feature of TSC, with seizures often occurring after the diagnosis of TSC has already been made. The mTOR pathway has been studied in animal models, with evidence suggesting that downstream effectors may contribute to the mechanisms leading to seizure generation, making the mTOR pathway an attractive candidate for potentially novel and rational antiepileptogenic therapies. PMID- 26854693 TI - Hepatic differentiation of human pluripotent stem cells on human liver progenitor HepaRG-derived acellular matrix. AB - Human hepatocytes are extensively needed in drug discovery and development. Stem cell-derived hepatocytes are expected to be an improved and continuous model of human liver to study drug candidates. Generation of endoderm-derived hepatocytes from human pluripotent stem cells (hPSCs), including human embryonic stem cells and induced pluripotent stem cells, is a complex, challenging process requiring specific signals from soluble factors and insoluble matrices at each developmental stage. In this study, we used human liver progenitor HepaRG-derived acellular matrix (ACM) as a hepatic progenitor-specific matrix to induce hepatic commitment of hPSC-derived definitive endoderm (DE) cells. The DE cells showed much better attachment to the HepaRG ACM than other matrices tested and then differentiated towards hepatic cells, which expressed hepatocyte-specific makers. We demonstrate that Matrigel overlay induced hepatocyte phenotype and inhibited biliary epithelial differentiation in two hPSC lines studied. In conclusion, our study demonstrates that the HepaRG ACM, a hepatic progenitor-specific matrix, plays an important role in the hepatic differentiation of hPSCs. PMID- 26854694 TI - The microRNA-dependent cell fate of multipotent stromal cells differentiating to endothelial cells. AB - In the endothelial recovery process, bone marrow-derived MSCs are a potential source of cells for both research and therapy, and their capacities to self-renew and to differentiate into all the cell types in the human body make them a promising therapeutic agent for remodeling cellular differentiation and a valuable resource for the treatment of many diseases. Based on the results provided in a miRNA database, we selected miRNAs with unique targets in cell fate related signaling pathways. The tested miRNAs targeting GSK-3beta (miR-26a), platelet-derived growth factor receptor, and CD133 (miR-26a and miR-29b) induced MSC differentiation into functional ECs, whereas miRNAs targeting VEGF receptor (miR-15, miR-144, miR-145, and miR-329) inhibited MSC differentiation into ECs through VEGF stimulation. In addition, the expression levels of these miRNAs were correlated with in vivo physiological endothelial recovery processes. These findings indicate that the miRNA expression profile is distinct for cells in different stages of differentiation from MSCs to ECs and that specific miRNAs can function as regulators of endothelialization. PMID- 26854695 TI - How does the metallothionein induction in bivalves meet the criteria for biomarkers of metal exposure? AB - Metallothionein (MT) concentrations in the whole soft tissue or in a particular tissue of bivalves have widely been used in ecotoxicological studies and biomonitoring programmes. This approach is based on the reported results on the enhancement of MT induction in bivalves in response to metal exposure. The validity of using MT induction as a biomarker is briefly assessed in the present study. The sensitivity of MT induction in these organisms is questionable due to the high basal MT level as well as the high natural variability related to the effects of a number of biotic and abiotic factors, which are not well described yet. Moreover, the relationship between exposure to metals, the toxic effects of that exposure, and the appearance of MT in soft tissue, is not well characterized. A variety of factors may influence the appearance and distribution of MT: 1) the uneven distribution of metals in particular portions of the soft tissue and in particular subcellular compartments; 2) pre-exposure to metals, perhaps at non-toxic levels; 3) metal-metal competition and metal-protein interactions; and 4) tissue-specific induction, functions, and isoforms of MT. Therefore, attention is required when using MT induction in bivalves for assessment of metal exposure or consequent toxic effects. The MT concentration can be a reliable indicator only when it is considered in relation with metal uptake kinetics and subcellular partitioning while specifying the isoform of MT synthesised and considering various confounding factors. The kinetic turnover of MT may provide useful information on metal exposure and biological effects since it covers both the synthesis and breakdown of MT as well as the chemical species of metals accumulated and MT. PMID- 26854696 TI - Long-term variation of black carbon and PM2.5 in Beijing, China with respect to meteorological conditions and governmental measures. AB - Black carbon (BC) and PM2.5 were studied for nine years from 2005 to 2013 in the Beijing urban area. The overall weekly average mass concentrations of BC and PM2.5 were 4.3 and 66.8 MUg/m3. PM2.5 annual means of the nine years are around 2 times of the standard (GB3095-2012) in China, and are 5-7 times higher than the WHO standard. The Beijing Olympic Games in 2008 was a milestone to mitigate aerosol pollution. Temporal distribution of BC shows a distinct declining trend, and annual mean mass concentrations of PM2.5 after 2008 were lower than those before 2008 but increased from 2011 to 2013. Wind rose plots show that high BC concentrations are usually associated with low wind speed of northeastern or southwestern winds, generally causing poor visibility. Governmental mitigation measures such as traffic restriction despite increased motor vehicle numbers and gasoline consumption and industry relocation with declining consumption of coal and coke were successful in reducing BC emissions. Annual mean of BC was reduced by 38% in 2013 compared to 2005. However, BC contamination in Beijing is still severe when compared to other urban areas around the world. PMID- 26854697 TI - Conifer density within lake catchments predicts fish mercury concentrations in remote subalpine lakes. AB - Remote high-elevation lakes represent unique environments for evaluating the bioaccumulation of atmospherically deposited mercury through freshwater food webs, as well as for evaluating the relative importance of mercury loading versus landscape influences on mercury bioaccumulation. The increase in mercury deposition to these systems over the past century, coupled with their limited exposure to direct anthropogenic disturbance make them useful indicators for estimating how changes in mercury emissions may propagate to changes in Hg bioaccumulation and ecological risk. We evaluated mercury concentrations in resident fish from 28 high-elevation, sub-alpine lakes in the Pacific Northwest region of the United States. Fish total mercury (THg) concentrations ranged from 4 to 438 ng/g wet weight, with a geometric mean concentration (+/-standard error) of 43 +/- 2 ng/g ww. Fish THg concentrations were negatively correlated with relative condition factor, indicating that faster growing fish that are in better condition have lower THg concentrations. Across the 28 study lakes, mean THg concentrations of resident salmonid fishes varied as much as 18-fold among lakes. We used a hierarchal statistical approach to evaluate the relative importance of physiological, limnological, and catchment drivers of fish Hg concentrations. Our top statistical model explained 87% of the variability in fish THg concentrations among lakes with four key landscape and limnological variables: catchment conifer density (basal area of conifers within a lake's catchment), lake surface area, aqueous dissolved sulfate, and dissolved organic carbon. Conifer density within a lake's catchment was the most important variable explaining fish THg concentrations across lakes, with THg concentrations differing by more than 400 percent across the forest density spectrum. These results illustrate the importance of landscape characteristics in controlling mercury bioaccumulation in fish. PMID- 26854698 TI - Adsorption-uptake-metabolism kinetic model on the removal of BDE-47 by a Chlorella isolate. AB - Polybrominated diphenyl ethers (PBDEs) are persistent and toxic organic pollutants, causing hazardous to ecosystems and human health but are difficult to remove from contaminated environments. The mechanism and kinetics of a Chlorella isolate to remove BDE-47 were investigated. This species isolated from the influent of wastewater treatment plants in Hong Kong was PBDE tolerant. More than 80% of BDE-47 was removed in short- and long-term experiments lasting 1 h and 7 days, respectively. The dominant removal process was adsorption on cell surfaces, with 73% of the spiked BDE-47 removed within five minutes of exposure. As the exposure prolonged, the adsorption became saturated. BDE-47 on cell surfaces was then gradually taken up into cells. At the end of the 7-day exposure, 17% of the spiked BDE-47 was within cells, while 27% was metabolized. Four metabolites, including BDE-28, 6-OH- and 5-OH-BDE-47, and 6-MeO-BDE-47, were produced from the debromination, hydroxylation and methoxylation of BDE-47. The removal kinetics of BDE-47 by freshwater microalgae could be explained by the multi-compartmental adsorption-uptake-metabolism model developed in this study. PMID- 26854699 TI - Increased zinc and copper availability in organic waste amended soil potentially involving distinct release mechanisms. AB - This study aimed at determining the fate of trace elements (TE) following soil organic waste (OW) application. We used a unique combination of X-ray absorption spectroscopy analyses, to determine TE speciation, with incubation experiments for in situ monitoring of TE availability patterns over a time course with the technique of the diffusive gradients in thin films (DGT). We showed that copper (Cu) and zinc (Zn) availability were both increased in OW-amended soil, but their release was controlled by distinct mechanisms. Zn speciation in OW was found to be dominated by an inorganic species, i.e. Zn sorbed on Fe oxides. Zn desorption from Fe oxides could explain the increase in Zn availability in OW-amended soil. Cu speciation in OW was dominated by organic species. Cu release through the mineralization of organic carbon from OW was responsible for the increase in Cu availability. PMID- 26854700 TI - Influence of trophic ecology on the accumulation of dioxins and furans (PCDD/Fs), non-ortho polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) in Mediterranean gulls (Larus michahellis and L. audouinii): A three isotope approach. AB - The impact of pollution caused by severe anthropogenic pressure in the Mediterranean Sea, an important biodiversity hotspot, requires continuous research efforts. Sources of highly toxic chemicals such as Persistent Organic Pollutants (POPs) are misunderstood in representative Mediterranean species, which limits our capability to establish proper conservation strategies. In the present study, eggs of Audouin's and yellow-legged gulls (Larus audouinii and L. michahellis) were used to investigate the trophic sources, as measured by delta(13)C, delta(15)N, and delta(34)S, of legacy POPs, in particular, polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) and non-ortho polychlorinated biphenyls (no-PCBs), as well as recently-regulated POPs, e.g., polybrominated diphenyl ethers (PBDEs). Special attention was paid to the usefulness of rarely-explored delta(34)S ratios in explaining POP exposure in wildlife, and delta(34)S was the isotopic ratio that best explained POP variations among gulls in most cases, thus demonstrating its usefulness for understanding POP exposure in wildlife. Significant relationships between stable isotope signatures and POP concentrations revealed increasing levels of no-PCBs and low halogenated PCDD/Fs and PBDEs in Mediterranean gulls as the consumption of marine resources increases. In contrast, highly chlorinated and brominated congeners appeared to preferentially accumulate in gulls feeding primarily on refuse from dump sites and terrestrial food webs. The use of suitable dietary tracers in the study of POPs in yellow-legged gulls revealed the importance of dump sites as a source of POPs in Mediterranean seabirds, which has not previously been reported. In contrast, the preferential accumulation through marine food webs of low chlorinated PCCD/Fs and no-PCBs, which show the highest toxic equivalents factors (TEFs), led to a significantly greater toxicological concern in Audouin's as compared to yellow-legged gulls. Audouin's gull exposure to POPs appears primarily related to the pelagic food webs commonly exploited by fisheries, highlighting the need for further research given the potential impact on human consumption. PMID- 26854701 TI - Trophic transfer of nano-TiO2 in a paddy microcosm: A comparison of single-dose versus sequential multi-dose exposures. AB - In the present study, replicated paddy microcosm systems were used to investigate the environmental fate and trophic transfer of titanium nanoparticles (NPs) over a period of 14 days. Most TiO2 NPs immediately settled down in the sediment, and high accumulations of nano TiO2 in the sandy loam sediment and biofilm were observed. The test organisms (quillworts, water dropworts, duckweeds, biofilms, river snails, and Chinese muddy loaches) and environmental media (freshwater, sandy loam sediment) were exposed to sequential low doses (2 mg/L at 1 h, 4 days, and 9 days) or a single high-dose (6 mg/L) of TiO2 NPs. The bioconcentration factors (BCFs) of nano-TiO2 in biofilms, quillworts, duckweeds, and Chinese muddy loaches were higher in the sequential multi-dose group than in the single-dose group. Chinese muddy loaches showed higher bioaccumulation factors (BAFs) over their prey than river snails. The difference in the carbon isotope ratios between Chinese muddy loaches and river snails was less than 20/00, and an approximately 40/00 difference in the stable nitrogen isotope ratio was observed in the two aquatic predators from their major prey (e.g., biofilms or particulate organic matter). The trophic levels between biofilms and river snails and between biofilms and Chinese muddy loaches were 2.8 and 2.4 levels, respectively. These results indicate that these two predators consumed biofilm and other alternative preys at a higher level than biofilm. Although the trophic transfer rates of TiO2 are generally low, relatively higher biomagnification factors (BMFs) were found in Chinese muddy loaches (0.04-0.05) than in river snails (0.01-0.02). These results suggest that TiO2 NPs show greater movement in the sediment than in the water and that TiO2 NPs can be retained through aquatic food chains more after a sequential low-dose exposure than after a single high-dose exposure. PMID- 26854702 TI - Predicting chronic copper and nickel reproductive toxicity to Daphnia pulex pulicaria from whole-animal metabolic profiles. AB - The emergence of omics approaches in environmental research has enhanced our understanding of the mechanisms underlying toxicity; however, extrapolation from molecular effects to whole-organism and population level outcomes remains a considerable challenge. Using environmentally relevant, sublethal, concentrations of two metals (Cu and Ni), both singly and in binary mixtures, we integrated data from traditional chronic, partial life-cycle toxicity testing and metabolomics to generate a statistical model that was predictive of reproductive impairment in a Daphnia pulex-pulicaria hybrid that was isolated from an historically metal stressed lake. Furthermore, we determined that the metabolic profiles of organisms exposed in a separate acute assay were also predictive of impaired reproduction following metal exposure. Thus we were able to directly associate molecular profiles to a key population response - reproduction, a key step towards improving environmental risk assessment and management. PMID- 26854703 TI - Occurrence of Dechlorane compounds and polybrominated diphenyl ethers (PBDEs) in the Korean general population. AB - Dechlorane compounds, including Dechlorane Plus (DP), mirex, and Dechlorane (Dec) 602, 603 and 604, were measured in 61 serum samples collected from a Korean urban area (Seoul) in 2013. Dechlorane Plus and Dec 602 were dominant in most samples, whereas Dec 604 was not detected in any samples. The median value of DP was 0.75 ng/g lipid, which was comparable with the levels observed in Europe and Canada, but lower than that observed in China. Statistically significant correlations among Dechlorane compounds were observed. The median anti-isomer fractional abundance (fanti) was 0.74, and a negative correlation between fanti and the DP concentration in serum samples was observed. Polybrominated diphenyl ethers (PBDEs) were also measured for comparison with Dechlorane compounds, and BDE-153 was found the most abundant congener with a median value of 1.43 ng/g lipid. A time trend of Dechlorane compounds was investigated in 7 pooled serum samples to cover the period from 2006 to 2013. A distinct trend of Dechlorane compounds was not observed, while PBDEs steadily decreased with time. PMID- 26854704 TI - Long-term impacts of nitrogen deposition on coastal plant communities. AB - Nitrogen deposition has been shown to have significant impacts on a range of vegetation types resulting in eutrophication and species compositional change. Data from a re-survey of 89 coastal sites in Scotland, UK, c. 34 years after the initial survey were examined to assess the degree of change in species composition that could be accounted for by nitrogen deposition. There was an overall increase in the Ellenberg Indicator Value for nitrogen (EIV-N) of 0.15 between the surveys, with a clear shift to species characteristic of more eutrophic situations. This was most evident for Acid grassland, Fixed dune, Heath, Slack and Tall grass mire communities and despite falls in EIV-N for Improved grass, Strand and Wet grassland. The increase in EIV-N was highly correlated to the cumulative deposition between the surveys, and for sites in south-east Scotland, eutrophication impacts appear severe. Unlike other studies, there appears to have been no decline in species richness associated with nitrogen deposition, though losses of species were observed on sites with the very highest levels of SOx deposition. It appears that dune vegetation (specifically Fixed dune) shows evidence of eutrophication above 4.1 kg N ha(-1) yr(-1), or 5.92 kg N ha(-1) yr(-1) if the lower 95% confidence interval is used. Coastal vegetation appears highly sensitive to nitrogen deposition, and it is suggested that major changes could have occurred prior to the first survey in 1976. PMID- 26854706 TI - Optomechanical Enhancement of Doubly Resonant 2D Optical Nonlinearity. AB - Emerging two-dimensional semiconductor materials possess a giant second order nonlinear response due to excitonic effects while the monolayer thickness of such active materials limits their use in practical nonlinear devices. Here, we report 3300 times optomechanical enhancement of second harmonic generation from a MoS2 monolayer in a doubly resonant on-chip optical cavity. We achieve this by engineering the nonlinear light-matter interaction in a microelectro-mechanical system enabled optical frequency doubling device based on an electrostatically tunable Fabry-Perot microresonator. Our versatile optomechanical approach will pave the way for next generation efficient on-chip tunable light sources, sensors, and systems based on molecularly thin materials. PMID- 26854705 TI - Diffuse Large B-Cell Lymphoma: Prospective Multicenter Comparison of Early Interim FLT PET/CT versus FDG PET/CT with IHP, EORTC, Deauville, and PERCIST Criteria for Early Therapeutic Monitoring. AB - Purpose To compare the performance characteristics of interim fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) (after two cycles of chemotherapy) by using the most prominent standardized interpretive criteria (including International Harmonization Project [IHP] criteria, European Organization for Research and Treatment of Cancer [EORTC] criteria, and PET Response Criteria in Solid Tumors (PERCIST) versus those of interim (18)F fluorothymidine (FLT) PET/CT and simple visual interpretation. Materials and Methods This HIPAA-compliant prospective study was approved by the institutional review boards, and written informed consent was obtained. Patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) underwent both FLT and FDG PET/CT 18-24 days after two cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone or rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin. For FDG PET/CT interpretation, IHP criteria, EORTC criteria, PERCIST, Deauville criteria, standardized uptake value, total lesion glycolysis, and metabolic tumor volume were used. FLT PET/CT images were interpreted with visual assessment by two reviewers in consensus. The interim (after cycle 2) FDG and FLT PET/CT studies were then compared with the end-of-treatment FDG PET/CT studies to determine which interim examination and/or criteria best predicted the result after six cycles of chemotherapy. Results From November 2011 to May 2014, there were 60 potential patients for inclusion, of whom 46 patients (24 men [mean age, 60.9 years +/- 13.7; range, 28-78 years] and 22 women [mean age, 57.2 years +/- 13.4; range, 25-76 years]) fulfilled the criteria. Thirty-four patients had complete response, and 12 had residual disease at the end of treatment. FLT PET/CT had a significantly higher positive predictive value (PPV) (91%) in predicting residual disease than did any FDG PET/CT interpretation method (42%-46%). No difference in negative predictive value (NPV) was found between FLT PET/CT (94%) and FDG PET/CT (82%-95%), regardless of the interpretive criteria used. FLT PET/CT showed statistically higher (P < .001-.008) or similar NPVs than did FDG PET/CT. Conclusion Early interim FLT PET/CT had a significantly higher PPV than standardized FDG PET/CT based interpretation for therapeutic response assessment in DLBCL. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26854707 TI - Type 1 and Type 2 Diabetes Preconception and in Pregnancy: Health Impacts, Influence of Obesity and Lifestyle, and Principles of Management. AB - Preexisting diabetes in pregnancy results in increased risks to the mother, fetus, and neonate. Preconception care is vital to reduce risk of miscarriage, congenital malformations, and perinatal mortality. Preconception care should empower women with realistic goal setting, healthy lifestyle, and diabetes self management skills, to ensure a positive experience of the pregnancy and to reduce diabetes-related distress. In high-risk women without known diabetes, preconception and early antenatal screening is crucial to enable prompt treatment of hyperglycemia and any complications. The prevalence of obesity in reproductive age women is rising, further increasing risk of poor pregnancy outcomes in women with diabetes. Adverse lifestyle factors should be addressed preconception and in the antenatal period, allowing opportunity to improve physical health, manage weight, and improve neonatal outcomes. Management of diabetes in pregnancy involves individualized and intensified insulin therapy, accounting for expected changes in insulin sensitivity, and minimizing glucose variability and hypoglycemia. Diabetes complications must be screened for and managed as necessary. Delivery timing will depend on fetal surveillance and obstetric considerations. It is important to maintain engagement and motivation of these women in the postpartum period, encouraging breastfeeding and postpartum weight management and supporting diabetes management. PMID- 26854708 TI - Fixed or Rotating Night Shift Work Undertaken by Women: Implications for Fertility and Miscarriage. AB - This review summarizes the evidence concerning effects of night shift work on women's reproductive health, specifically difficulty in conceiving and miscarriage. We distinguish between fixed night shift and rotating night shift, as the population subgroups exposed, the social and biological mechanisms, and the magnitude of effects are likely to differ; of note, women working fixed night shift are known to have high tolerance for this schedule. We identified two relevant systematic reviews with meta-analyses and five additional studies. Night shift work may give rise to menstrual cycle disturbances, but effect sizes are imprecise. Endometriosis may be elevated in night shift workers, but evidence is only preliminary. Adequate data are lacking to assess associations between night shift work and infertility or time to pregnancy. The weight of evidence begins to point to working at night, whether in fixed or rotating shifts, as a risk factor for miscarriage. There are many methodological problems with this literature, with substantial variation in the definitions of night shift and schedule types making comparisons between studies difficult and pooling across studies questionable. Nevertheless, there appears to be grounds for caution and counselling where women have concerns about night shift work and their reproductive health. PMID- 26854709 TI - Polycystic Ovary Syndrome, Obesity, and Pregnancy. AB - Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting up to one in five reproductive-aged women. It is underpinned by insulin resistance and hyperandrogenism and is associated with metabolic, reproductive, and psychological features. Women with PCOS have higher rates of obesity and central adiposity compared with women without PCOS, and weight strongly influences prevalence and clinical severity of PCOS. Women with PCOS may have subfertility and women should be aware of factors affecting fertility, in particular the impact of obesity and age. Once pregnant, women with PCOS have significantly increased risk of pregnancy-related complications including gestational diabetes, hypertensive disorders, premature delivery, and delivery by cesarean section. The offspring of women with PCOS may have increased risk of congenital abnormalities and hospitalization in childhood. Clinicians should be aware of the increased risk and screen, prevent, and manage accordingly. PMID- 26854710 TI - Lifestyle Factors Focused on Diet and Physical Activity: Recommendations Preconception and During Pregnancy. PMID- 26854711 TI - Perrin and Forster unified: Dual-laser triple-polarization FRET (3polFRET) for interactions at the Forster-distance and beyond. AB - Dual laser flow cytometric energy transfer (FCET)--elaborated by Tron et al. in 1984--is an efficient and rapid way of measuring FRET on large cell populations. FRET efficiency and the donor and acceptor concentrations are determined from one donor and two acceptor signals. In this communication this method is extended towards the domain of receptor dynamics by the detection of polarized components of the three intensities. By enabling a complete description of the proximity and dynamics of FRET-systems, the new measuring scheme allows a more refined description of both the structure and dynamics of cell surface receptor clusters at the nano-scale and beyond. Associated donor fraction, limiting anisotropy and rotational correlation time of the donor, acceptor anisotropy and cell-by-cell estimation of the orientation factor for FRET (kappa2) are available in the steady state on a single FRET sample in a very rapid and statistically efficient way offered by flow cytometry. For a more sensitive detection of conformational changes the "polarized FRET indices"--quantities composed from FRET efficiency and anisotropies--are proposed. The method is illustrated by measurements on a FRET system with changing FRET-fraction and on a two donor-one acceptor-system, when the existence of receptor trimers are proven by the detection of "hetero FRET induced homo-FRET relief", i.e. the diminishing of homo-FRET between the two donors in the presence of a donor quencher. The method also offers higher sensitivity for assessing conformational changes at the nano-scale, due to its capability for the simultaneous detection of changes of proximity and relative orientations of the FRET donor and acceptor. Although the method has been introduced in the context of FRET, it is more general: It can be used for monitoring triple-anisotropy correlations also in those cases when FRET actually does not occur, e.g. for interactions occuring beyond the Forster-distance R0. Interpretation of kappa2 has been extended. PMID- 26854712 TI - Facile construction of vertically aligned ZnO nanorod/PEDOT:PSS hybrid heterojunction-based ultraviolet light sensors: efficient performance and mechanism. AB - We demonstrate a simple, planar manufacturing process-compatible fabrication of highly efficient UV sensors based on a hybrid heterojunction of an array of vertically aligned ZnO nanorods (NRs) and PEDOT: PSS. The ZnO NR array was grown by the solution growth process and the aspect ratio (length 1 to 4 MUm, diameter ~80 nm) of the rods was controlled by varying the growth time. UV sensors based on (i) naked ZnO NRs and (ii) ZnO NR/PEDOT:PSS heterojunctions were fabricated and tested. The UV sensitivity of bare ZnO NRs was found to increase with increasing aspect ratio of the NRs due to the increase in the photogenerated charge carriers as the fraction of material interacting with the light increases. Under 5 V bias, naked ZnO NR arrays showed a photocurrent of 8.84 * 10(-5) A, a responsivity of 0.538 A W(-1) and a sensitivity of 4.80 under UV (lambda = 256 nm, 130 MUW) illumination. ZnO NR/PEDOT:PSS hybrid heterojunctions showed diode like behavior with a leakage current less than 2.54 * 10(-8) A at -5 V and forward turn-on voltage of 1.1 V. ZnO NR/polymer-based hybrid heterojunctions show a photocurrent of 6.74 * 10(-4) A, responsivity of 5.046 A W(-1) and excellent sensitivity of 37.65 under UV (lambda = 256 nm, 130 MUW) illumination. Compared with bare ZnO NR arrays, the ZnO NR/polymer heterojunction device shows responsivity enhanced by a factor of 10, sensitivity enhanced by a factor of 8 and faster rise and decay time. The enhanced performance may be due to effective charge separation guided by the built-in potential formed at the interface between ZnO NRs and PEDOT: PSS. PMID- 26854713 TI - Cell Growth Dynamics in Embryonic and Adult Mouse Thyroid Revealed by a Novel Approach to Detect Thyroid Gland Subpopulations. AB - BACKGROUND: The thyroid is composed of endocrine epithelial cells, blood vessels, and mesenchyme. However, no data exist thus far on absolute cell numbers, relative distribution, and proliferation of the different cell populations in the developing and mature thyroid. The aim of this study was therefore to establish a flow cytometry protocol that allows detection and quantification of discrete cell populations in embryonic and adult murine thyroid tissues. METHODS: Cell-type anti-mouse specific antibodies were used for erythroid cells (Ter119), hematopoietic cells (CD45), epithelial cells (EpCam/CD326, E-cadherin/CD324), thyroid follicular cells and C-cells (Nkx2-1), endothelial cells (Pecam/CD31, Icam-1/CD54), and fibroblasts (PDGFRa/CD140a). Proliferating cells were detected after labeling with 5-bromo-2'-deoxyuridine (BrdU). For flow cytometry analyses, micro-dissected embryonic (E) and adult thyroids were pooled (E13.5, n = 25; E15.5, n = 15; E17.5, n = 15; adult, n = 4) in one sample. RESULTS: The absolute parenchymal cell numbers per mouse thyroid (M +/- SD), excluding the large number of CD45(+) and Ter119(+) cells, increased from 7425 +/- 1338 at E13.5 to 271,561 +/- 22,325 in adult tissues. As expected, Nkx2-1(+) cells represented the largest cell population in adult tissues (61.2 +/- 1.1%). Surprisingly, at all three embryonic stages analyzed, thyroid follicular cells and C-cells accounted only for a small percentage of the total thyroid cell mass (between 4.7 +/- 0.4% and 9.4 +/- 1.6%). In contrast, the largest cell population at all three embryonic stages was identified as PDGFRa/CD140a(+) fibroblasts (61.4 +/- 0.4% to 77.3 +/- 1.1%). However, these cells represented the smallest population in adult tissues (5.2 +/- 0.8%). Pecam/CD31(+) endothelial cells increased from E13.5 to E15.5 from 3.7 +/- 0.8% to 8.5 +/- 3.0%, then remained stable at E17.5 and adult tissues. Proliferation rates were sizable during the entire organogenesis but differed between cell populations, with distinct proliferative peaks at E13.5 in epithelial cells (32.7 +/- 0.6% BrdU(+) cells), and at E15.5 in endothelial cells (22.4 +/- 2.4% BrdU(+) cells). Fibroblasts showed a constant proliferation rate in embryonic tissues. In adult tissues, BrdU(+) cells were between 0.1% and 0.4% in all cell types. CONCLUSIONS: Using a novel flow cytometry-based method, a previously unobserved highly dynamic growth pattern of thyroid cell populations during embryogenesis was uncovered. This approach will provide a useful new tool for cell function analyses in murine thyroid disease models. PMID- 26854714 TI - ALDOA functions as an oncogene in the highly metastatic pancreatic cancer. AB - Pancreatic cancer is an aggressive and devastating disease that is characterized by uncontrolled progression, invasiveness and resistance to conventional treatment. In the past decades, much effort has been given to cancer genetics and pathological classification of this disease. Our previous study has uncovered a subgroup of patients with poor outcome, which is characterized by serum signature of CEA(+)/CA125(+)/CA19-9 >= 1000 U/mL; however, the underlying biology mechanism remains poorly understood. By using high-throughput screening analysis, we analyzed gene expression signature in highly malignant patients with serum markers of CEA(+)/CA125(+)/CA19-9 >= 1000 U/mL. Multiple differentially expressed genes were identified, many of which were closely related with cancer metabolic changes. Treatment of pancreatic cancer cell lines PANC-1 with transforming growth factor-beta (TGF-beta), which was commonly used to induce metastasis, has uncovered that the glycolytic process and antioxidant response was up-regulated upon TGF-beta stimulation. These results were consistent with the high-throughput screening analysis. Subsequent analysis indicated that among glycolytic genes, aldolase A (ALDOA) increased the most significantly upon TGF-beta treatment. Further in vitro and in vivo results demonstrated that ALDOA was associated with proliferation and metastasis of pancreatic cancer cells. Moreover, ALDOA predicted poor prognosis of pancreatic cancer, partially due to its role in E cadherin expression regulation, and the results were further validated by analysis of the correlation between ALDOA and E-cadherin expression in pancreatic cancer tissue samples. Mechanistically, the role of ALDOA in pancreatic cancer might attribute to its regulation of c-Myc, HIF1alpha and NRF2 (Nuclear Factor, Erythroid 2-Like 2), which were key regulators of glycolysis and antioxidant response control. PMID- 26854715 TI - A tumor-suppressive microRNA, miR-504, inhibits cell proliferation and promotes apoptosis by targeting FOXP1 in human glioma. AB - MicroRNAs (miRNAs) have been proposed as useful prognostic cancer biomarkers and as potential molecular targets for treating various cancers. Previous findings have indicated that miR-504 is dysregulated and involved in tumorigenesis of several types of cancer. However, the biological role of miR-504 in glioma remains unclear. In this study, we showed that miR-504 expression was markedly decreased in both glioma tissues and cell lines and that miR-504 downregulation significantly correlated with aggressive clinicopathological features and poor prognosis for glioma patients. In addition, miR-504 overexpression inhibited cell proliferation, induced cell cycle arrest, and promoted apoptosis in glioma cell lines. Furthermore, we identified forkhead box protein P1 (FOXP1) as a direct target of miR-504 using microarray analysis and a luciferase assay. Moreover, we demonstrated that miR-504 regulated glioma tumorigenesis by downregulating FOXP1 expression. Our results suggest that miR-504 might function as an important suppressor of glioma tumorigenesis and could serve as a promising candidate for therapeutic applications in glioma treatment. PMID- 26854716 TI - Plasma cell-free DNA levels and integrity in patients with chest radiological findings: NSCLC versus benign lung nodules. AB - Effective discrimination between lung cancer and benign tumours is a common clinical problem in the differential diagnosis of solitary pulmonary nodules. The analysis of cell-free DNA (cfDNA) in blood may greatly aid the early detection of lung cancer by evaluating cancer-related alterations. The plasma cfDNA levels and integrity were analysed in 65 non-small cell lung cancer (NSCLC) patients, 28 subjects with benign lung tumours, and 16 healthy controls using real-time PCR. The NSCLC patients demonstrated significantly higher mean plasma cfDNA levels compared with those with benign tumours (P = 0.0009) and healthy controls (P < 0.0001). The plasma cfDNA integrity in healthy individuals was significantly different than that found in patients with NSCLC or benign lung tumours (P < 0.0003). In ROC curve analysis, plasma cfDNA levels >2.8 ng/ml provided 86.4% sensitivity and 61.4% specificity in discriminating NSCLC from benign lung pathologies and healthy controls. cfDNA integrity showed better discriminatory power (91% sensitivity, 68.2% specificity). These data demonstrate that plasma cfDNA concentration and integrity analyses can significantly differentiate between NSCLC and benign lung tumours. The diagnostic capacity of the quantitative cfDNA assay is comparable to the values presented by conventional imaging modalities used in clinical practice. PMID- 26854717 TI - Development of highly efficient nanocarrier-mediated delivery approaches for cancer therapy. AB - Nanocarriers (NCs) are a group of nano-sized vehicles devised to deliver drugs to targeted malignant tissues or organs that provide remarkably improved targeting efficiency and therapeutic efficacy for cancer therapy. A variety of NCs have been developed to accommodate appropriate loading and release of drugs with a wide spectrum of chemical and physical characteristics. In addition, physicochemical modifications to the surface or interior of NCs allow for modulation of pharmacokinetic features reflecting clinical demands. However, cancer-related mortality is still high and drug-mediated cancer treatment remains a challenging research field despite the remarkable advances in targeting efficiency and therapeutic efficacy resulting from NCs. In this review, we focus on typical approaches and recent trends in NC-mediated drug delivery systems and their potential for targeted cancer therapy. PMID- 26854718 TI - Pristimerin triggers AIF-dependent programmed necrosis in glioma cells via activation of JNK. AB - Programmed necrosis is established as a new form of programmed cell death and is emerging as a new strategy of treatment for cancers. Pristimerin is a natural chemical with anti-tumor effect despite the fact that its mechanism remains poorly understood. In this study, we used glioma cell lines and mice model of xenograft glioma to investigate the effect of pristimerin on glioma and its underlying mechanism. We found that pristimerin inhibited the viabilities of glioma cells in vitro and the growth of xenograft gliomas in vivo, which was accompanied by upregulation of JNK and phosphor-JNK, nuclear accumulation of AIF, and elevation in the ratio of Bax/Bcl-2. In vitro studies showed that pristimerin induced necrosis in glioma cells, as well as mitochondrial depolarization, overproduction of ROS and reduction of GSH. Ablation of AIF level with SiRNA mitigated pristimerin-induced nuclear accumulation of AIF and prevented necrosis in glioma cells. Moreover, pharmacological inhibition of JNK with SP600125 or knockdown of its level with SiRNA reversed mitochondrial depolarization attenuated the elevation of Bax/Bcl-2 and suppressed nuclear accumulation of AIF. Further, inhibition of ROS with NAC not only rescued glioma cell necrosis but also suppressed JNK activation, mitigated Bax/Bcl-2 ratio, maintained mitochondrial membrane potential, and inhibited AIF translocation into nucleus. Therefore, we demonstrated first in this study that pristimerin triggered AIF dependent necroptosis in glioma cells via induction of mitochondrial dysfunction by activation of JNK through overproduction of ROS. These results suggest that pristimerin has potential therapeutic effects on glioma. PMID- 26854719 TI - Rheumatoid arthritis is still expensive in the new decade: a comparison between two early RA cohorts, diagnosed 1996-98 and 2006-09. AB - OBJECTIVES: To calculate total costs during the first year after diagnosis in 463 patients with early rheumatoid arthritis (RA) included during 2006-09 (T2) and compare the results with a similar cohort included in 1996-98 (T1). METHOD: Clinical and laboratory data were collected regularly in both cohorts, and patients completed biannual questionnaires reporting health care utilization and number of days lost from work. RESULTS: Disease activity was similar in both cohorts T1 and T2 at inclusion. Significant improvements were seen during the first year in both cohorts but were more pronounced in T2. Outpatient care increased and hospitalization decreased in T2 compared with T1. Almost 3% of patients had surgery in both cohorts, but in T2, only women had surgery. Drug costs were higher in T2 than in T1 (EUR 689 vs. EUR 435). In T2, 12% of drug costs were direct costs and 4% were total costs. The corresponding values for T1 were 9% and 3%. In T1, 50% were prescribed disease-modifying anti-rheumatic drugs (DMARDs) at inclusion, compared to T2, where prescription was > 90%. Direct costs were EUR 5716 in T2 and EUR 4674 in T1. Costs for sick leave were lower in T2 than in T1 (EUR 5490 vs. EUR 9055) but disability pensions were higher (EUR 4152 vs. EUR 2139), resulting in unchanged total costs. In T1, direct costs comprised 29% and indirect costs 71% of the total costs. The corresponding values for T2 were 37% and 63%. CONCLUSIONS: The earlier and more aggressive treatment of RA with traditional DMARDs in T2 resulted in better outcomes compared to T1. Direct costs were higher in T2, partly offset by decreased sick leave, but total costs remained unchanged. PMID- 26854720 TI - Nonsurgical treatment of an epulis by photodynamic therapy. PMID- 26854721 TI - 5'-Spiro-cyclopropanated lactose derivatives as suitable intermediates for the chain elongation: synthesis of a new 6-deoxy-6-methyl delta-eptulose. AB - A delta-dicarbonyl heptose has been prepared through an electrophilic ring opening procedure of a 5'-spirocyclopropanated lactose derivative. The reported synthetic procedure outlines a new route for the transformation of this renewable disaccharide into new and interesting delta-dicarbonyl sugars, synthetic precursors of cyclitols, carba- and azasugars. The experimental results of the cyclopropanation process have been successfully rationalized by in silico studies. PMID- 26854722 TI - Molecule specific effects of PKA-mediated phosphorylation on rat isolated heart and cardiac myofibrillar function. AB - Increased cardiac myocyte contractility by the beta-adrenergic system is an important mechanism to elevate cardiac output to meet hemodynamic demands and this process is depressed in failing hearts. While increased contractility involves augmented myoplasmic calcium transients, the myofilaments also adapt to boost the transduction of the calcium signal. Accordingly, ventricular contractility was found to be tightly correlated with PKA-mediated phosphorylation of two myofibrillar proteins, cardiac myosin binding protein-C (cMyBP-C) and cardiac troponin I (cTnI), implicating these two proteins as important transducers of hemodynamics to the cardiac sarcomere. Consistent with this, we have previously found that phosphorylation of myofilament proteins by PKA (a downstream signaling molecule of the beta-adrenergic system) increased force, slowed force development rates, sped loaded shortening, and increased power output in rat skinned cardiac myocyte preparations. Here, we sought to define molecule-specific mechanisms by which PKA-mediated phosphorylation regulates these contractile properties. Regarding cTnI, the incorporation of thin filaments with unphosphorylated cTnI decreased isometric force production and these changes were reversed by PKA-mediated phosphorylation in skinned cardiac myocytes. Further, incorporation of unphosphorylated cTnI sped rates of force development, which suggests less cooperative thin filament activation and reduced recruitment of non-cycling cross-bridges into the pool of cycling cross-bridges, a process that would tend to depress both myocyte force and power. Regarding MyBP C, PKA treatment of slow-twitch skeletal muscle fibers caused phosphorylation of MyBP-C (but not slow skeletal TnI (ssTnI)) and yielded faster loaded shortening velocity and ~30% increase in power output. These results add novel insight into the molecular specificity by which the beta-adrenergic system regulates myofibrillar contractility and how attenuation of PKA-induced phosphorylation of cMyBP-C and cTnI may contribute to ventricular pump failure. PMID- 26854724 TI - MicroRNA-26a-5p regulates the expression of inducible nitric oxide synthase via activation of NF-kappaB pathway in human osteoarthritis chondrocytes. AB - Inducible nitric oxide synthase (iNOS) expression is associated with the pathogenesis of osteoarthritis (OA). This study was undertaken to investigate whether interleukin-1beta (IL-1beta)-mediated induction of iNOS can be regulated by microRNA-26a-5p (hsa-miR-26a-5p) in OA. Bioinformatics approaches show that 3'UTR of iNOS mRNA contained the 'seed-matched-sequence' for hsa-miR-26a-5p. IL 1beta-induced expression of iNOS correlated with the down-regulation of miR-26a 5p in human OA chondrocytes. hsa-miR-26a-5p directly suppressed the luciferase activity of 3'UTR-iNOS reporter clone. Transfection with pre-miR-26a-5p induced marked silencing of iNOS expression. Activation of NF-kappaB pathway down regulated the expression of hsa-miR-26a-5p and induced iNOS expression. In short, this is the first report that shows hsa-miR-26a-5p is a direct regulator of iNOS expression in human chondrocytes. hsa-miR-26a-5p may be an important regulator of human cartilage homeostasis and a new target for OA therapy. PMID- 26854723 TI - Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4). AB - Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid. PMID- 26854726 TI - Linear solvation energy relationship for the adsorption of synthetic organic compounds on single-walled carbon nanotubes in water. AB - The linear solvation energy relationship (LSER) was applied to predict the adsorption coefficient (K) of synthetic organic compounds (SOCs) on single-walled carbon nanotubes (SWCNTs). A total of 40 log K values were used to develop and validate the LSER model. The adsorption data for 34 SOCs were collected from 13 published articles and the other six were obtained in our experiment. The optimal model composed of four descriptors was developed by a stepwise multiple linear regression (MLR) method. The adjusted r(2) (r(2)adj) and root mean square error (RMSE) were 0.84 and 0.49, respectively, indicating good fitness. The leave-one out cross-validation Q(2) ([Formula: see text]) was 0.79, suggesting the robustness of the model was satisfactory. The external Q(2) ([Formula: see text]) and RMSE (RMSEext) were 0.72 and 0.50, respectively, showing the model's strong predictive ability. Hydrogen bond donating interaction (bB) and cavity formation and dispersion interactions (vV) stood out as the two most influential factors controlling the adsorption of SOCs onto SWCNTs. The equilibrium concentration would affect the fitness and predictive ability of the model, while the coefficients varied slightly. PMID- 26854725 TI - Insights into length-dependent regulation of cardiac cross-bridge cycling kinetics in human myocardium. AB - Cross-bridge cycling kinetics play an essential role in the heart's ability to contract and relax. The rate of tension redevelopment (ktr) slows down as a muscle length is increased in intact human myocardium. We set out to determine the effect of rapid length step changes and protein kinase A (PKA) and protein kinase C-betaII (PKC-betaII) inhibitors on the ktr in ultra-thin non-failing and failing human right ventricular trabeculae. After stabilizing the muscle either at L90 (90% of optimal length) or at Lopt (optimal length), we rapidly changed the length to either Lopt or L90 and measured ktr. We report that length dependent changes in ktr occur very rapidly (in the order of seconds or faster) in both non-failing and failing muscles and that the length at which a muscle had been stabilized prior to the length change does not significantly affect ktr. In addition, at L90 and at Lopt, PKA and PKC-betaII inhibitors did not significantly change ktr. Our results reveal that length-dependent regulation of cross-bridge cycling kinetics predominantly occurs rapidly and involves the intrinsic properties of the myofilament rather than post-translational modifications that are known to occur in the cardiac muscle as a result of a change in muscle/sarcomere length. PMID- 26854727 TI - The selectivity and promiscuity of brain-neuroregenerative inhibitors between ROCK1 and ROCK2 isoforms: An integration of SB-QSSR modelling, QM/MM analysis and in vitro kinase assay. AB - The Rho-associated kinases (ROCKs) have long been recognized as an attractive therapeutic target for various neurological diseases; selective inhibition of ROCK1 and ROCK2 isoforms would result in distinct biological effects on neurogenesis, neuroplasticity and neuroregeneration after brain surgery and traumatic brain injury. However, the discovery and design of isoform-selective inhibitors remain a great challenge due to the high conservation and similarity between the kinase domains of ROCK1 and ROCK2. Here, a structure-based quantitative structure-selectivity relationship (SB-QSSR) approach was used to correlate experimentally measured selectivity with the difference in inhibitor binding to the two kinase isoforms. The resulting regression models were examined rigorously through both internal cross-validation and external blind validation; a nonlinear predictor was found to have high fitting stability and strong generalization ability, which was then employed to perform virtual screening against a structurally diverse, drug-like compound library. Consequently, five and seven hits were identified as promising candidates of 1-o-2 and 2-o-1 selective inhibitors, respectively, from which seven purchasable compounds were tested in vitro using a standard kinase assay protocol to determine their inhibitory activity against and selectivity between ROCK1 and ROCK2. The structural basis, energetic property and biological implication underlying inhibitor selectivity and promiscuity were also investigated systematically using a hybrid quantum mechanics/molecular mechanics (QM/MM) scheme. PMID- 26854728 TI - Predicting binding affinities of diverse pharmaceutical chemicals to human serum plasma proteins using QSPR modelling approaches. AB - The prediction of the plasma protein binding (PPB) affinity of chemicals is of paramount significance in the drug development process. In this study, ensemble machine learning-based QSPR models have been established for a four-category classification and PPB affinity prediction of diverse compounds using a large PPB dataset of 930 compounds and in accordance with the OECD guidelines. The structural diversity of the chemicals was tested by the Tanimoto similarity index. The external predictive power of the developed QSPR models was evaluated through internal and external validations. In the QSPR models, XLogP was the most important descriptor. In the test data, the classification QSPR models rendered an accuracy of >93%, while the regression QSPR models yielded r(2) of >0.920 between the measured and predicted PPB affinities, with the root mean squared error <9.77. Values of statistical coefficients derived for the test data were above their threshold limits, thus put a high confidence in this analysis. The QSPR models in this study performed better than any of the previous studies. The results suggest that the developed QSPR models are reliable for predicting the PPB affinity of structurally diverse chemicals. They can be useful for initial screening of candidate molecules in the drug development process. PMID- 26854729 TI - Screen time, weight status and the self-concept of physical attractiveness in adolescents. AB - Adolescents in modern societies spend about 3 h per day in front of small recreational screens. The present study aims at investigating the relationships between screen time and different indicators of overweight. In addition, associations with the self-concept of physical attractiveness and perceived weight status will be examined. In a total sample of 1228 students (47.5% girls) aged 12-17 years (M = 13.74, SD = 0.68) cross-sectional associations were determined by conducting multiple linear regression analyses. Screen time showed a significant positive dose-response relationship with body mass index percentile, waist circumference, body fat, waist-to-height-ratio, and a negative association with self-concept of physical attractiveness independent of age, gender and moderate to vigorous physical activity. Thus, screen time seems to be associated with adolescent overweight, abdominal obesity, and body dissatisfaction. Reducing adolescents' screen time could be a promising approach for primary prevention of obesity and for the promotion of a positive physical self-concept. PMID- 26854730 TI - Energy-efficient Compressed Sensing for ambulatory ECG monitoring. AB - Advances in Compressed Sensing (CS) are enabling promising low-energy implementation solutions for wireless Body Area Networks (BAN). While studies demonstrate the potential of CS in terms of overall energy efficiency compared to state-of-the-art lossy compression techniques, the performance of CS remains limited. The aim of this study is to improve the performance of CS-based compression for electrocardiogram (ECG) signals. This paper proposes a CS architecture that combines a novel redundancy removal scheme with quantization and Huffman entropy coding to effectively extend the Compression Ratio (CR). Reconstruction is performed using overcomplete sparse dictionaries created with Dictionary Learning (DL) techniques to exploit the highly structured nature of ECG signals. Performance of the proposed CS implementation is evaluated by analyzing energy-based distortion metrics and diagnostic metrics including QRS beat-detection accuracy across a range of CRs. The proposed CS approach offers superior performance to the most recent state-of-the-art CS implementations in terms of signal reconstruction quality across all CRs tested. Furthermore, QRS detection accuracy of the technique is compared with the well-known lossy Set Partitioning in Hierarchical Trees (SPIHT) compression technique. The proposed CS approach outperforms SPIHT in terms of achievable CR, using the area under the receiver operator characteristic (ROC) curve (AUC). For an application where a minimum AUC performance threshold of 0.9 is required, the proposed technique extends the CR from 64.6 to 90.45 compared with SPIHT, ensuring a 40% saving on wireless transmission costs. Therefore, the results highlight the potential of the proposed technique for ECG computer-aided diagnostic systems. PMID- 26854731 TI - Metabolic and redox barriers in the skin exposed to drugs and xenobiotics. AB - INTRODUCTION: Growing exposure of human skin to environmental and occupational hazards, to numerous skin care/beauty products, and to topical drugs led to a biomedical concern regarding sustainability of cutaneous chemical defence that is essential for protection against intoxication. Since skin is the largest extra hepatic drug/xenobiotic metabolising organ where redox-dependent metabolic pathways prevail, in this review, publications on metabolic processes leading to redox imbalance (oxidative stress) and its autocrine/endocrine impact to cutaneous drug/xenobiotic metabolism were scrutinised. AREAS COVERED: Chemical and photo-chemical skin barriers contain metabolic and redox compartments: their protective and homeostatic functions. The review will examine the striking similarity of adaptive responses to exogenous chemical/photo-chemical stressors and endogenous toxins in cutaneous metabolic and redox system; the role(s) of xenobiotics/drugs and phase II enzymes in the endogenous antioxidant defence and maintenance of redox balance; redox regulation of interactions between metabolic and inflammatory responses in skin cells; skin diseases sharing metabolic and redox problems (contact dermatitis, lupus erythematosus, and vitiligo) EXPERT OPINION: Due to exceptional the redox dependence of cutaneous metabolic pathways and interaction of redox active metabolites/exogenous antioxidants with drug/xenobiotic metabolism, metabolic tests of topical xenobiotics/drugs should be combined with appropriate redox analyses and performed on 3D human skin models. PMID- 26854732 TI - Effect of magnesium sulfate and thyroxine on inflammatory markers in a rat model of hypothyroidism. AB - Inflammation is a major risk factor for cardiovascular complications. Magnesium sulfate (MgSO4) has anti-inflammatory actions. Therefore we investigated the effects of levothyroxine and MgSO4 on inflammatory markers as C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in hypothyroid rats. Sixty male rats were divided into 6 groups; normal, normal + MgSO4, hypothyroidism, hypothyroidism + levothyroxine, hypothyroidism + MgSO4, and hypothyroidism + levothyroxine + MgSO4. Thyroxine, triiodothyronine, and thyroid-stimulating hormone (TSH), CRP, interleukin-6, TNF-alpha, ICAM-1, and VCAM-1 were measured in all rats. Hypothyroidism significantly increased TSH, CRP, interleukin-6, TNF-alpha, ICAM-1, and VCAM-1 and decreased triiodothronine and thyroxine. Treatment of hypothyroid rats with levothyroxine or MgSO4 significantly decreased CRP, interleukin-6, TNF-alpha, ICAM-1, and VCAM-1. Combined therapy of hypothyroid rats with levothyroxine and MgSO4 significantly decreased CRP, interleukin-6, TNF-alpha, ICAM-1, and VCAM-1 compared with hypothyroid rats either untreated or treated with levothyroxine or MgSO4. This study demonstrates that hypothyroid rats have chronic low grade inflammation, which may account for increased risk of cardiovascular diseases. Combined levothyroxine and MgSO4 is better than levothyroxine or MgSO4 alone in alleviating the chronic low grade inflammatory status and therefore reducing the risk of cardiovascular diseases in hypothyroid animals. PMID- 26854733 TI - Get It through Your Thick Head: Emerging Principles in Neuroimmunology and Neurovirology Redefine Central Nervous System "Immune Privilege". AB - The central nervous system (CNS) coordinates all aspects of life, autonomic and sentient, though how it has evolved to contend with pathogenic infections remains, to a great degree, a mystery. The skull and cerebrospinal fluid (CSF) provide protection from blunt force contacts, and it was once thought that the blood-brain barrier (BBB) was a fortress that restricted pathogen entry and limited inflammation. Recent studies, however, have caused a revision of this viewpoint: the CNS is monitored by blood-borne lymphocytes, but can use alternative strategies to prevent or resolve many pathogenic challenges. In this Review, we discuss emerging principles that indicate how the CNS is immunologically unique from peripheral tissues. We focus on developments that include glymphatics, recently characterized brain lymphatic vessels, distinctions in innate and adaptive immune strategies, novel points of entry for neurotropic viruses, and, finally, how the periphery can influence CNS homeostasis and immune responses within the brain. Collectively, these attributes demand a re-evaluation of immunity in the brain: not privileged, but distinct. PMID- 26854735 TI - Altered S-nitrosothiol homeostasis provides a survival advantage to breast cancer cells in HER2 tumors and reduces their sensitivity to trastuzumab. AB - The monoclonal antibody trastuzumab against HER2/neu, which is overexpressed in 15-20% of breast cancers, has clinical efficacy but many patients do not respond to initial treatment or develop resistance during treatment. Nitric oxide (NO) regulates cell signaling by targeting specific cysteine residues in proteins, forming S-nitrosothiols (SNO) in a process known as S-nitrosylation. We previously reported that molecular characteristics in breast cancer may dictate the tumor response to impaired SNO homeostasis. In the present study, we explored the role of SNO homeostasis in HER2 breast tumors. The antiproliferative action of trastuzumab in HER2-overexpressing BT-474 and SKBR-3 cells was suppressed when S-nitrosoglutathione reductase (GSNOR/ADH5) activity, which plays a key role in SNO homeostasis, was specifically inhibited with the pyrrole derivative compound N6022. Moreover, GSNOR inhibition restored the activation of survival signaling pathways involved in the resistance to anti-HER2 therapies (AKT, Src and c-Abl kinases and TrkA/NRTK1, TrkB/NRTK2, EphA1 and EphA3 receptors) and reduced the apoptotic effect of trastuzumab. Accordingly, GSNOR inhibition augmented the S nitrosylation of apoptosis-related proteins, including Apaf-1, pSer73/63 c-Jun, calcineurin subunit alpha and HSF1. In agreement with in vitro data, immunohistochemical analyses of 51 breast tumors showed that HER2 expression was associated with lower expression of GSNOR protein. Moreover, gene expression analysis confirmed that high ADH5/GSNOR gene expression was associated with high patient survival rates in HER2 tumors. In conclusion, our data provide evidence of molecular mechanisms contributing to the progression of HER2+ breast cancers and could facilitate the development of therapeutic options to counteract resistance to anti-HER2 therapies. PMID- 26854734 TI - Effects of alanine:glyoxylate aminotransferase variants and pyridoxine sensitivity on oxalate metabolism in a cell-based cytotoxicity assay. AB - The hereditary kidney stone disease primary hyperoxaluria type 1 (PH1) is caused by a functional deficiency of the liver-specific, peroxisomal, pyridoxal phosphate-dependent enzyme, alanine:glyoxylate aminotransferase (AGT). One third of PH1 patients, particularly those expressing the p.[(Pro11Leu; Gly170Arg; Ile340Met)] mutant allele, respond clinically to pharmacological doses of pyridoxine. To gain further insight into the metabolic effects of AGT dysfunction in PH1 and the effect of pyridoxine, we established an "indirect" glycolate cytotoxicity assay using CHO cells expressing glycolate oxidase (GO) and various normal and mutant forms of AGT. In cells expressing GO the great majority of glycolate was converted to oxalate and glyoxylate, with the latter causing the greater decrease in cell survival. Co-expression of normal AGTs and some, but not all, mutant AGT variants partially counteracted this cytotoxicity and led to decreased synthesis of oxalate and glyoxylate. Increasing the extracellular pyridoxine up to 0.3MUM led to an increased metabolic effectiveness of normal AGTs and the AGT-Gly170Arg variant. The increased survival seen with AGT Gly170Arg was paralleled by a 40% decrease in oxalate and glyoxylate levels. These data support the suggestion that the effectiveness of pharmacological doses of pyridoxine results from an improved metabolic effectiveness of AGT; that is the increased rate of transamination of glyoxylate to glycine. The indirect glycolate toxicity assay used in the present study has potential to be used in cell-based drug screening protocols to identify chemotherapeutics that might enhance or decrease the activity and metabolic effectiveness of AGT and GO, respectively, and be useful in the treatment of PH1. PMID- 26854736 TI - Association between nutritional status and outcomes in critically-ill pediatric patients - a systematic review. AB - OBJECTIVES: To systematically review the evidence about the impact of nutritional status in critically-ill pediatric patients on the following outcomes during hospitalization in pediatric intensive care units: length of hospital stay, need for mechanical ventilation, and mortality. DATA SOURCE: The search was carried out in the following databases: Lilacs (Latin American and Caribbean Health Sciences), MEDLINE (National Library of Medicine United States) and Embase (Elsevier Database). No filters were selected. RESULTS: A total of seven relevant articles about the subject were included. The publication period was between 1982 and 2012. All articles assessed the nutritional status of patients on admission at pediatric intensive care units and correlated it to at least one assessed outcome. A methodological quality questionnaire created by the authors was applied, which was based on some references and the researchers' experience. All included studies met the quality criteria, but only four met all the items. CONCLUSION: The studies included in this review suggest that nutritional depletion is associated with worse outcomes in pediatric intensive care units. However, studies are scarce and those existing show no methodological homogeneity, especially regarding nutritional status assessment and classification methods. Contemporary and well-designed studies are needed in order to properly assess the association between children's nutritional status and its impact on outcomes of these patients. PMID- 26854737 TI - Reprint of "Potential seminal transport of pharmaceuticals to the conceptus". AB - Small molecule pharmaceutical products are assumed to reach concentrations in semen similar to those in blood plasma. Exposure modeling for these small molecule products in humans assumes a daily dose of 5mL of semen and 100% absorption from the vagina with distribution to the conceptus through the maternal systemic circulation. Monoclonal antibody drugs are present in semen at concentrations about 2% or less of those in blood, and the modeling used for small molecules will over-estimate the possibility of conceptus exposure to immunoglobulins. It is not known whether peptide products reach semen, but in general peptide medications are destroyed by vaginal peptidases, and conceptus exposure is predicted to be minimal. Theoretical exposure routes to pharmaceuticals that might result in exposure of the conceptus greater than that of maternal systemic exposures include direct access through the cervical canal, adsorption to sperm for carriage into the oocyte, and direct delivery from the vaginal veins or lymphatics to the uterine artery. There is some evidence for direct access to the uterus for progesterone, terbutaline, and danazol, but the evidence does not involve exposures during pregnancy in most instances. Studies in mice, rats, rabbits, and monkeys do not suggest that exposure to small molecule pharmaceuticals in semen imposes risks to the conceptus beyond those that can be predicted using modeling of systemic maternal exposure. Monoclonal antibody and peptide exposure in semen does not pose a significant risk to the conceptus. PMID- 26854738 TI - Regarding corneal decompensation in recessive cornea plana. PMID- 26854740 TI - Anterior sacral meningocele presenting as right adnexal cyst. PMID- 26854739 TI - Sunlight Irradiation of Highly Brominated Polyphenyl Ethers Generates Polybenzofuran Products That Alter Dioxin-responsive mRNA Expression in Chicken Hepatocytes. AB - We report on two highly brominated polyphenyl ether flame retardants, tetradecabromo-1,4- diphenoxybenzene (TeDB-DiPhOBz) and 2,2',3,3',4,4',5,5',6,6' decabromodiphenyl ether (BDE-209), that formed photolytic degradation products in tetrahydrofuran (THF)/hexane solvent after 21 days of natural sunlight irradiation (SI). These degradation products of SI-TeDB-DiPhOBz and SI-BDE-209 included the numerous polybrominated homologue groups of polybenzofurans and dibenzofurans, respectively. Formation of similar polybenzofuran and dibenzofuran products was also observed following a 3 month exposure of the solid powder forms of TeDB-DiPhOBz and BDE-209 to natural SI. These resulting degradation product mixtures were administered to chicken embryonic hepatocytes (CEH) to determine effects on mRNA expression levels of 27 dioxin-responsive genes. For the solvent based SI study, equivalent concentrations of 1 or 25 MUM of SI-TeDB-DiPhOBz or 1 or 10 MUM of SI-BDE-209 resulted in gene expression profiles that were similar to those of the most potent dioxin-like compound, 2,3,7,8-tetrachlorodibenzo-p dioxin. In addition, a concentration-dependent induction of CYP1A4 and CYP1A5 mRNA was observed following exposure to SI-TeDB-DiPhOBz and SI-BDE-209. Based on ECthreshold values for CYP1A4/5 mRNA expression, relative potency (ReP) values were 1 * 10(-6) and 1 * 10(-5) for SI-TeDB-DiPhOBz and SI-BDE-209, respectively. The SI TeDB-DiPhOBz and BDE-209 powder degradation product mixture also significantly induced CYP1A4 mRNA levels in CEH. Our findings clearly show that the environmental stability of TeDB-DiPhOBz and BDE-209, and possibly other highly brominated polyphenyl ethers, is of great concern from a dioxin-like degradation products and toxicity perspective. PMID- 26854741 TI - Skill acquisition via motor imagery relies on both motor and perceptual learning. AB - Motor imagery (MI), the mental rehearsal of movement, is an effective means for acquiring a novel skill, even in the absence of physical practice (PP). The nature of this learning, be it perceptual, motor, or both, is not well understood. Understanding the mechanisms underlying MI-based skill acquisition has implications for its use in numerous disciplines, including informing best practices regarding its use. Here we used an implicit sequence learning (ISL) task to probe whether MI-based skill acquisition can be attributed to perceptual or motor learning. Participants (n = 60) randomized to 4 groups were trained through MI or PP, and were then tested in either perceptual (altering the sensory cue) or motor (switching the hand) transfer conditions. Control participants (n = 42) that did not perform a transfer condition were utilized from previous work. Learning was quantified through effect sizes for reaction time (RT) differences between implicit and random sequences. Generally, PP-based training led to lower RTs compared with MI-based training for implicit and random sequences. All groups demonstrated learning (p < .05), the magnitude of which was reduced by transfer conditions relative to controls. For MI-based training perceptual transfer disrupted performance more than for PP. Motor transfer disrupted performance equally for MI- and PP-based training. Our results suggest that MI-based training relies on both perceptual and motor learning, while PP-based training relies more on motor processes. These results reveal details regarding the mechanisms underlying MI, and inform its use as a modality for skill acquisition. (PsycINFO Database Record PMID- 26854742 TI - Determining the relationship between sleep architecture, seizure variables and memory in patients with focal epilepsy. AB - Sleep has been shown to be important to memory. Both sleep and memory have been found to be abnormal in patients with epilepsy. In this study, we explored the effects that nocturnal epileptiform discharges and the presence of a hippocampal lesion have on sleep patterns and memory. Twenty-five patients with focal epilepsy who underwent a 24-hr ambulatory EEG also completed the Everyday Memory Questionnaire (EMQ). The EEG record was scored for length of time spent in the various sleep stages, time spent awake after sleep onset, and rapid eye movement (REM) latency. Of these sleep variables, only REM latency differed when the epilepsy patients were divided on the bases of either presence/absence of nocturnal discharges or presence/absence of a hippocampal lesion. In both cases, presence of the abnormality was associated with longer latency. Furthermore, longer REM latency was found to be a better predictor of EMQ score than either number of discharges or presence of a hippocampal lesion. Longer REM latency was associated with a smaller percentage of time spent in slow-wave sleep in the early part of the night and may serve as a particularly sensitive marker to disturbances in sleep architecture. (PsycINFO Database Record PMID- 26854743 TI - Advances in microfluidics in combating infectious diseases. AB - One of the important pursuits in science and engineering research today is to develop low-cost and user-friendly technologies to improve the health of people. Over the past decade, research efforts in microfluidics have been made to develop methods that can facilitate low-cost diagnosis of infectious diseases, especially in resource-poor settings. Here, we provide an overview of the recent advances in microfluidic devices for point-of-care (POC) diagnostics for infectious diseases and emphasis is placed on malaria, sepsis and AIDS/HIV. Other infectious diseases such as SARS, tuberculosis, and dengue are also briefly discussed. These infectious diseases are chosen as they contribute the most to disability-adjusted life-years (DALYs) lost according to the World Health Organization (WHO). The current state of research in this area is evaluated and projection toward future applications and accompanying challenges are also discussed. PMID- 26854745 TI - FTIR, Raman, and XPS analysis during phosphate, nitrate and Cr(VI) removal by amine cross-linking biosorbent. AB - This study explores the potential use of amine cross-linked reed (ACR) for removing nitrate, phosphate and Cr(VI) from aqueous in a fixed-bed column. Characteristics (surface area, pore structure, FTIR, Raman spectra, XPS, zeta potential and solid NMR) of ACR as well as anions laden samples were intensively investigated. Results indicated that FTIR, Raman and XPS of nitrate and phosphate laden ACR were quite different from those of Cr(VI) laden samples, which corresponded well to their adsorption properties. Tertiary amine group played the main role in uptake of nitrate and phosphate by electrostatic attraction. Characteristics of Cr(VI) laden samples indicated that a reduction of Cr(VI) to Cr(III) occurred on surface of ACR (this was also proved by the zeta potential analysis). However, the main adsorption mechanism for Cr(VI) onto ACR was still based on electrostatic attraction. The maximum dynamic adsorption capacity of ACR for nitrate, phosphate and Cr(VI) was estimated to be 118.9 mg/g, 103.1mg/g and 135.3mg/g. The nitrate/phosphate adsorption capacities of spent ACR after 3 cycles of adsorption-desorption were recovered with 97.3-98.4%. In contrast, only 49.2% of Cr(VI) recovery was achieved, partially due to the destruction of the functional groups on surface of ACR during the Cr(VI) adsorption. PMID- 26854744 TI - Analysis of the role of the LH92_11085 gene of a biofilm hyper-producing Acinetobacter baumannii strain on biofilm formation and attachment to eukaryotic cells. AB - Acinetobacter baumannii is a nosocomial pathogen that has a considerable ability to survive in the hospital environment partly due to its capacity to form biofilms. The first step in the process of establishing an infection is adherence of the bacteria to target cells. Chaperone-usher pili assembly systems are involved in pilus biogenesis pathways that play an important role in adhesion to host cells and tissues as well as medically relevant surfaces. After screening a collection of strains, a biofilm hyper-producing A. baumannii strain (MAR002) was selected to describe potential targets involved in pathogenicity. MAR002 showed a remarkable ability to form biofilm and attach to A549 human alveolar epithelial cells. Analysis of MAR002 using transmission electron microscopy (TEM) showed a significant presence of pili on the bacterial surface. Putative protein-coding genes involved in pili formation were identified based on the newly sequenced genome of MAR002 strain (JRHB01000001/2 or NZ_JRHB01000001/2). As assessed by qRT PCR, the gene LH92_11085, belonging to the operon LH92_11070-11085, is overexpressed (ca. 25-fold more) in biofilm-associated cells compared to exponential planktonic cells. In the present work we investigate the role of this gene on the MAR002 biofilm phenotype. Scanning electron microscopy (SEM) and biofilm assays showed that inactivation of LH92_11085 gene significantly reduced bacterial attachment to A549 cells and biofilm formation on plastic, respectively. TEM analysis of the LH92_11085 mutant showed the absence of long pili formations normally present in the wild-type. These observations indicate the potential role this LH92_11085 gene could play in the pathobiology of A baumannii. PMID- 26854746 TI - Synthesis of hydrophobic cross-linked polyzwitterionic acid for simultaneous sorption of Eriochrome black T and chromium ions from binary hazardous waters. AB - Hydrophobic cross-linked polyzwitterionic acid (HCPZA) containing long chain (C18) hydrophobes and residues of a glutamic acid having unquenched nitrogen valency was synthesized. Exploiting the chelating ability of the amino acid residues to scavenge toxic metals and the hydrophobic surface to scoop up the organic contaminants, the resin HCPZA was evaluated for simultaneous removal of chromium and Eriochrome black T (EBT) from wastewaters. The structure and morphology of the polymer before and after sorption were characterized by using FTIR, TGA, EDX and SEM. The effect of various parameters such as contact time, pH and initial concentrations were investigated to arrive at optimum conditions. The adsorption of Eriochrome black T and Cr (III) on HCPZA reached equilibrium in 30 min. The mechanism of adsorption was investigated using kinetic, diffusion and isotherm models. The adsorption kinetic data were described well by the pseudo second order model and by the Freundlich isotherm model. EDX analysis confirmed the adsorption of Cr (III) and EBT on the polymer. The hydrophobic resin exhibited a remarkable simultaneous adsorption capacity for EBT and Cr (III) and thus demonstrated its potential to be a promising adsorbent for removal of dyes and heavy metal ions from wastewaters. PMID- 26854747 TI - DNA-Encoded Library Screening Identifies Benzo[b][1,4]oxazepin-4-ones as Highly Potent and Monoselective Receptor Interacting Protein 1 Kinase Inhibitors. AB - The recent discovery of the role of receptor interacting protein 1 (RIP1) kinase in tumor necrosis factor (TNF)-mediated inflammation has led to its emergence as a highly promising target for the treatment of multiple inflammatory diseases. We screened RIP1 against GSK's DNA-encoded small-molecule libraries and identified a novel highly potent benzoxazepinone inhibitor series. We demonstrate that this template possesses complete monokinase selectivity for RIP1 plus unique species selectivity for primate versus nonprimate RIP1. We elucidate the conformation of RIP1 bound to this benzoxazepinone inhibitor driving its high kinase selectivity and design specific mutations in murine RIP1 to restore potency to levels similar to primate RIP1. This series differentiates itself from known RIP1 inhibitors in combining high potency and kinase selectivity with good pharmacokinetic profiles in rodents. The favorable developability profile of this benzoxazepinone template, as exemplified by compound 14 (GSK'481), makes it an excellent starting point for further optimization into a RIP1 clinical candidate. PMID- 26854748 TI - Simeprevir/pegylated interferon/ribavirin triple therapy for recurrent hepatitis C after living donor liver transplantation. AB - AIM: Simeprevir (SMV) is a protease inhibitor which demonstrates good tolerability and high antiviral response in patients with hepatitis C. The clinical outcomes of triple therapy using simeprevir, pegylated interferon and ribavirin (SMV/PEG IFN/RBV) for recurrent hepatitis C after living donor liver transplantation (LDLT) have not been well reported. In this study, we assessed the outcomes of patients with recurrent hepatitis C (genotype 1) after LDLT who received triple therapy at our hospital. METHODS: SMV/PEG IFN/RBV was administrated for 12 weeks (triple therapy), followed by another 12 weeks or extended period of PEG IFN/RBV (dual therapy). Virological response, interaction with calcineurin inhibitors and adverse events were retrospectively analyzed. RESULTS: Ten patients with recurrent hepatitis C after LDLT completed 12 weeks of triple therapy. Nine patients achieved rapid or early virological response, and one patient was a non-responder. The nine responders received subsequent dual therapy, and the duration of dual therapy was extended (24 to 36 weeks) in five cases. Although one patient was in relapse 8 weeks after completing the standard duration (12 weeks) of dual therapy, eight patients achieved sustained virological response for 12 weeks (SVR12). The SVR12 rate was 80%. Trough levels of calcineurin inhibitor did not show marked changes after introduction of SMV in all cases. There were no major adverse events associated with SMV. CONCLUSION: SMV treatment may be a safe and effective option for recurrent hepatitis C after LDLT. PMID- 26854749 TI - Spontaneous bacterial peritonitis is a risk factor for renal failure requiring dialysis in waitlisted liver transplant candidates. AB - AIMS: To examine the relationship between and impact of spontaneous bacteria peritonitis (SBP) and renal failure requiring dialysis in waitlisted liver transplant (LT) candidates. BACKGROUND: Renal failure is a common and severe complication in cirrhotic patients with SBP. Approximately one-third of patients with SBP develop renal failure despite treatment of infection. However, the incidence of renal failure requiring dialysis in LT waitlisted patients who have developed SBP is unknown. The high mortality observed in this group has also raised debate about resource utilization in the care of these patients. METHODS: Data from the United Network for Organ Sharing Standard Transplant and Research files were collected retrospectively between 1994 and 2012. The primary endpoint measured was first time initiation of dialysis while on the LT wait list. Secondary endpoints included waitlist time and mortality on wait list. RESULTS: A total of 42,085 patients were included. SBP at time of listing was diagnosed in 2,352 patients (5.6%) and first time initiation of dialysis while on the wait list occurred in 2,367 patients (6.2%). Unadjusted OR for requiring dialysis for patients listed with SBP was 1.66 (p < 0.001). When controlled for age, gender, BMI, diabetes mellitus, baseline creatinine, MELD score, serum albumin at listing, the adjusted OR for dialysis was 1.24 (p = 0.007) in waitlisted patients with SBP. Patients with SBP at time of listing had a mean waitlist time 142.1 d vs. 198.7 d in non-SBP patients (p < 0.001). CONCLUSIONS: Spontaneous bacteria peritonitis patients have a significantly increased likelihood to require dialysis and mean shorter waitlist time. Furthermore, the combined occurrence of SBP and dialysis is a strong risk factor for all-cause mortality while on the LT wait list. PMID- 26854750 TI - Intestinal tuberculosis and Crohn's disease: challenging differential diagnosis. AB - Along with epidemiological changes in tuberculosis (TB) and an increased incidence of Crohn's disease (CD), the differential diagnosis of intestinal TB (ITB) and CD is of vital importance and has become a clinical challenge because treatment based on misdiagnosis may lead to fatal outcomes. In this study, we reviewed the similarities and differences in clinical, endoscopic, radiological and histological features of these two diseases. Concomitant pulmonary TB, ascites, night sweats, involvement of fewer than four segments of the bowel, patulous ileocecal valve, transverse ulcers, scars or pseudopolyps strongly indicate ITB. Bloody stools, perianal signs, chronic diarrhea, extraintestinal manifestations, anorectal lesions, longitudinal ulcers and a cobblestone appearance are all suggestive of CD. Significant differences in the size, number, location and patterns of granulomas in ITB and CD with regard to their histopathologic features have been noted. Immune stain of cell surface markers is also helpful. Interferon-gamma release assay and polymerase chain reaction analysis have achieved satisfactory sensitivity and specificity in the diagnosis of ITB. Computed tomography enterographic findings of segmental small bowel or left colon involvement, mural stratification, the comb sign and fibrofatty proliferation are significantly more common in CD, whereas mesenteric lymph node changes (calcification or central necrosis) and focal ileocecal lesions are more frequently seen in ITB. A diagnosis should be carefully established before the initiation of the therapy. In suspicious cases, short-term empirical anti-TB therapy is quite efficient to further confirm the diagnosis. PMID- 26854751 TI - Hurricane Isaac: A Longitudinal Analysis of Storm Characteristics and Power Outage Risk. AB - In August 2012, Hurricane Isaac, a Category 1 hurricane at landfall, caused extensive power outages in Louisiana. The storm brought high winds, storm surge, and flooding to Louisiana, and power outages were widespread and prolonged. Hourly power outage data for the state of Louisiana were collected during the storm and analyzed. This analysis included correlation of hourly power outage figures by zip code with storm conditions including wind, rainfall, and storm surge using a nonparametric ensemble data mining approach. Results were analyzed to understand how correlation of power outages with storm conditions differed geographically within the state. This analysis provided insight on how rainfall and storm surge, along with wind, contribute to power outages in hurricanes. By conducting a longitudinal study of outages at the zip code level, we were able to gain insight into the causal drivers of power outages during hurricanes. Our analysis showed that the statistical importance of storm characteristic covariates to power outages varies geographically. For Hurricane Isaac, wind speed, precipitation, and previous outages generally had high importance, whereas storm surge had lower importance, even in zip codes that experienced significant surge. The results of this analysis can inform the development of power outage forecasting models, which often focus strictly on wind-related covariates. Our study of Hurricane Isaac indicates that inclusion of other covariates, particularly precipitation, may improve model accuracy and robustness across a range of storm conditions and geography. PMID- 26854752 TI - Rapid T2 mapping of mouse heart using the carr-purcell-meiboom-gill sequence and compressed sensing reconstruction. AB - PURPOSE: To develop and prove preliminary validation of a fast in vivo T2 mapping technique for mouse heart. MATERIALS AND METHODS: Magnetic resonance imaging (MRI) experiments were performed on a 7T animal scanner. The standard Carr Purcell-Meiboom-Gill (CPMG) sequence was modified to minimize the effect of stimulated echoes for accurate T2 quantification. The acquisition was further accelerated with the compressed sensing approach. The accuracy of the proposed method was first validated with both phantom experiments and numerical simulations. In vivo T2 measurement was performed on seven mice in a manganese enhanced MRI study. RESULTS: In phantom studies, T2 values obtained with the modified CPMG sequence are in good agreement with the standard spin-echo method (P > 0.05). Numerical simulations further demonstrated that with the application of the compressed sensing approach, fast T2 quantification with a spatial resolution of 2.3 mm can be achieved at a high temporal resolution of 1 minute per slice. With the proposed technique, an average T2 value of 25 msec was observed for mouse heart at 7T and this number decreased significantly after manganese infusion (P < 0.001). CONCLUSION: A rapid T2 mapping technique was developed and assessed, which allows accurate T2 quantification of mouse heart at a temporal resolution of 1 minute per slice. J. Magn. Reson. Imaging 2016;44:375 382. PMID- 26854753 TI - Probing for thiol isomerase activity in thrombi. PMID- 26854754 TI - An integrated molecular landscape implicates the regulation of dendritic spine formation through insulin-related signalling in obsessive-compulsive disorder. AB - BACKGROUND: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with onset in childhood and is characterized by obsessions (recurrent, intrusive, persistent thoughts, impulses and/or ideas that often cause anxiety or distress) and compulsions (ritualized and stereotypic behaviours or mental acts that are often performed to relieve anxiety or distress associated with obsessions). Although OCD is a heritable disorder, its complex molecular etiology is poorly understood. METHODS: We combined enrichment analyses and an elaborate literature review of the top-ranked genes emerging from the 2 published genome-wide association studies of OCD and candidate genes implicated through other evidence in order to identify biological processes that, when dysregulated, increase the risk for OCD. RESULTS: The resulting molecular protein landscape was enriched for proteins involved in regulating postsynaptic dendritic spine formation - and hence synaptic plasticity - through insulin-dependent molecular signalling cascades. LIMITATIONS: This study is a first attempt to integrate molecuar information from different sources in order to identify biological mechanisms underlying OCD etiology. Our findings are constrained by the limited information from hypothesis-free studies and the incompleteness and existing limitations of the OCD literature and the gene function annotations of gene enrichment tools. As this study was solely based on in silico analyses, experimental validation of the provided hypotheses is warranted. CONCLUSION: Our work suggests a key role for insulin and insulin-related signalling in OCD etiology and - if confirmed by independent studies - could eventually pave the way for the development of novel OCD treatments. PMID- 26854755 TI - Global brain connectivity alterations in patients with schizophrenia and bipolar spectrum disorders. AB - BACKGROUND: The human brain is organized into functionally distinct modules of which interactions constitute the human functional connectome. Accumulating evidence has implicated perturbations in the patterns of brain connectivity across a range of neurologic and neuropsychiatric disorders, but little is known about diagnostic specificity. Schizophrenia and bipolar disorders are severe mental disorders with partly overlapping symptomatology. Neuroimaging has demonstrated brain network disintegration in the pathophysiologies; however, to which degree the 2 diagnoses present with overlapping abnormalities remains unclear. METHODS: We collected resting-state fMRI data from patients with schizophrenia or bipolar disorder and from healthy controls. Aiming to characterize connectivity differences across 2 severe mental disorders, we derived global functional connectivity using eigenvector centrality mapping, which allows for regional inference of centrality or importance in the brain network. RESULTS: Seventy-one patients with schizophrenia, 43 with bipolar disorder and 196 healthy controls participated in our study. We found significant effects of diagnosis in 12 clusters, where pairwise comparisons showed decreased global connectivity in high-centrality clusters: sensory regions in patients with schizophrenia and subcortical regions in both patient groups. Increased connectivity occurred in frontal and parietal clusters in patients with schizophrenia, with intermediate effects in those with bipolar disorder. Patient groups differed in most cortical clusters, with the strongest effects in sensory regions. LIMITATIONS: Methodological concerns of in-scanner motion and the use of full correlation measures may make analyses more vulnerable to noise. CONCLUSION: Our results show decreased eigenvector centrality of limbic structures in both patient groups and in sensory regions in patients with schizophrenia as well as increased centrality in frontal and parietal regions in both groups, with stronger effects in patients with schizophrenia. PMID- 26854757 TI - BRAF V600E detection in cytological thyroid samples: A key component of the decision tree for surgical treatment of papillary thyroid carcinoma. AB - BACKGROUND: Whether preoperative knowledge of the BRAF mutation status would help to determine the extent of surgery for thyroid nodules is still under investigation. METHODS: We developed a method to state the V600E mutation before surgery on fine-needle aspiration (FNA) stained smears checked to contain tumor cells. We evaluated the interest of the preoperative assessment of the mutation for surgical strategy of nodules, diagnosed as malignant, suspicious for malignancy or follicular neoplasms. RESULTS: The mutation was found in 81% (79 of 97) malignant, 59% (20 of 34) suspicious nodules, and in none of follicular neoplasms (n = 29). Overall, the mutation was detected in 82% of papillary carcinomas. The sensitivity, specificity, and positive and negative predictive values for the diagnosis of malignancy were 75%, 100%, 100%, and 46%, respectively. CONCLUSION: The preoperative knowledge of the V600E mutation status is fundamental to plan total thyroidectomy with certainty and should be part of the decision tree for the management of thyroid nodules. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1017-1021, 2016. PMID- 26854758 TI - Unraveling the Molecular Mechanism of pH-Induced Misfolding and Oligomerization of the Prion Protein. AB - The misfolding of the prion protein (PrP) to aggregated forms is linked to several neurodegenerative diseases. Misfolded oligomeric forms of PrP are associated with neurotoxicity and/or infectivity, but the molecular mechanism by which they form is still poorly understood. A reduction in pH is known to be a key factor that triggers misfolded oligomer formation by PrP, but the residues whose protonation is linked with misfolding remain unidentified. The structural consequences of the protonation of these residues also remain to be determined. In the current study, amino acid residues whose protonation is critical for PrP misfolding and oligomerization have been identified using site-directed mutagenesis and misfolding/oligomerization assays. It is shown that the protonation of either H186 or D201, which mimics the effects of pathogenic mutations (H186R and D201N) at both residue sites, is critically linked to the stability, misfolding and oligomerization of PrP. Hydrogen-deuterium exchange studies coupled with mass spectrometry show that the protonation of either H186 or D201 leads to the same common structural change: increased structural dynamics in helix 1 and that in the loop between helix 1 and beta-strand 2. It is shown that the protonation of either of these residues is sufficient for accelerating misfolded oligomer formation, most likely because the protonation of either residue causes the same structural perturbation. Hence, the increased structural dynamics in helix 1 and that in the loop between helix 1 and beta-strand 2 appear to play an early critical role in acid-induced misfolding of PrP. PMID- 26854756 TI - Dysfunctional insular connectivity during reward prediction in patients with first-episode psychosis. AB - BACKGROUND: Increasing evidence indicates that psychosis is associated with abnormal reward processing. Imaging studies in patients with first-episode psychosis (FEP) have revealed reduced activity in diverse brain regions, including the ventral striatum, insula and anterior cingulate cortex (ACC), during reward prediction. However, whether these reductions in local brain activity are due to altered connectivity has rarely been explored. METHODS: We applied dynamic causal modelling and Bayesian model selection to fMRI data during the Salience Attribution Task to investigate whether patients with FEP showed abnormal modulation of connectivity between the ventral striatum, insula and ACC induced by rewarding cues and whether these changes were related to positive psychotic symptoms and atypical antipsychotic medication. RESULTS: The model including reward-induced modulation of insula-ACC connectivity was the best fitting model in each group. Compared with healthy controls (n = 19), patients with FEP (n = 29) revealed reduced right insula-ACC connectivity. After subdividing patients according to current antipsychotic medication, we found that the reduced insula-ACC connectivity relative to healthy controls was observed only in untreated patients (n = 17), not in patients treated with antipsychotics (n = 12), and that it correlated negatively with unusual thought content in untreated patients with FEP. LIMITATIONS: The modest sample size of untreated patients with FEP was a limitation of our study. CONCLUSION: This study indicates that insula-ACC connectivity during reward prediction is reduced in untreated patients with FEP and related to the formation of positive psychotic symptoms. Our study further suggests that atypical antipsychotics may reverse connectivity between the insula and the ACC during reward prediction. PMID- 26854759 TI - Interactions between the Microtubule Binding Protein EB1 and F-Actin. AB - Many cellular processes including cell division and cell migration require coordination between the actin and microtubule (MT) cytoskeletons. This coordination is as-yet poorly understood, but proteins such as formins and IQGAP1 are known to be involved. We show that the MT binding protein EB1 (end-binding protein 1), a key regulator of MT dynamics, can bind directly to filamentous actin (F-actin) F-actin. We determined that the EB1:F-actin interaction is salt sensitive and weak under physiological salt concentrations but might be relevant in contexts where the local concentration of actin is high. Using bioinformatics and mutagenesis, we found that the EB1:F-actin binding site partially overlaps the well-characterized EB1:MT binding interface. Congruently, competition experiments indicate that EB1 can bind to F-actin or MTs but not both simultaneously. These observations suggest that EB1:F-actin interactions may negatively regulate EB1:MT interactions, and we speculate that this interaction may assist cells in differentially regulating MT stability in the actin-rich cortex as opposed to the cell interior. PMID- 26854761 TI - Early-life respiratory infections and asthma development: role in disease pathogenesis and potential targets for disease prevention. AB - PURPOSE OF REVIEW: This article presents recent findings and perspectives on the relationship between early-life respiratory infections and asthma inception, and discusses emerging concepts on strategies that target these infectious agents for asthma prevention. RECENT FINDINGS: Cumulative evidence supports the role of early-life viral infections, especially respiratory syncytial virus and human rhinovirus, as major antecedents of childhood asthma. These viruses may have different mechanistic roles in the pathogenesis of asthma. The airway microbiome and virus-bacteria interactions in early life have emerged as additional determinants of childhood asthma. Innovative strategies for the prevention of these early-life infections, or for attenuation of acute infection severity, are being investigated and may identify effective strategies for the primary and secondary prevention of childhood asthma. SUMMARY: Early-life infections are major determinants of asthma development. The pathway from early-life infections to asthma is the result of complex interactions between the specific type of the virus, genetic, and environmental factors. Novel intervention strategies that target these infectious agents have been investigated in proof-of-concepts trials, and further study is necessary to determine their capacity for asthma prevention. PMID- 26854760 TI - CryptoSite: Expanding the Druggable Proteome by Characterization and Prediction of Cryptic Binding Sites. AB - Many proteins have small-molecule binding pockets that are not easily detectable in the ligand-free structures. These cryptic sites require a conformational change to become apparent; a cryptic site can therefore be defined as a site that forms a pocket in a holo structure, but not in the apo structure. Because many proteins appear to lack druggable pockets, understanding and accurately identifying cryptic sites could expand the set of drug targets. Previously, cryptic sites were identified experimentally by fragment-based ligand discovery and computationally by long molecular dynamics simulations and fragment docking. Here, we begin by constructing a set of structurally defined apo-holo pairs with cryptic sites. Next, we comprehensively characterize the cryptic sites in terms of their sequence, structure, and dynamics attributes. We find that cryptic sites tend to be as conserved in evolution as traditional binding pockets but are less hydrophobic and more flexible. Relying on this characterization, we use machine learning to predict cryptic sites with relatively high accuracy (for our benchmark, the true positive and false positive rates are 73% and 29%, respectively). We then predict cryptic sites in the entire structurally characterized human proteome (11,201 structures, covering 23% of all residues in the proteome). CryptoSite increases the size of the potentially "druggable" human proteome from ~40% to ~78% of disease-associated proteins. Finally, to demonstrate the utility of our approach in practice, we experimentally validate a cryptic site in protein tyrosine phosphatase 1B using a covalent ligand and NMR spectroscopy. The CryptoSite Web server is available at http://salilab.org/cryptosite. PMID- 26854763 TI - Organosilane with Gemini-Type Structure as the Mesoporogen for the Synthesis of the Hierarchical Porous ZSM-5 Zeolite. AB - A new kind of organosilane (1,6-bis(diethyl(3-trimethoxysilylpropyl)ammonium) hexane bromide) with a gemini-type structure was prepared and used as a mesoporogen for the synthesis of hierarchical porous ZSM-5 zeolite. There are two quaternary ammonium centers along with double-hydrolyzable -RSi(OMe)3 fragments in the organosilane, which results in a strong interaction between this mesoporogen and silica-alumina gel. The organosilane can be easily incorporated into the ZSM-5 zeolite structure during the crystallization process, and it was finally removed by calcination, leading to secondary pores in ZSM-5. The synthesized ZSM-5 has been systematically studied by XRD, nitrogen adsorption, SEM, TEM, TG, and solid-state one-dimensional (1D) and two-dimensional (2D) NMR, which reveal information on its detailed structure. It has a hierarchical porosity system, which combines the intrinsic micropores coming from the crystalline structure and irregular mesopores created by the organosilane template. Moreover, the mesoposity including pore size and volume within ZSM-5 can be systematically tuned by changing the organosilane/TEOS ratio, which confirms that this organosilane has high flexibility of use as a template for the synthesis of hierarchical porous zeolite. PMID- 26854762 TI - DNA methylation and mRNA expression of HLA-DQA1 alleles in type 1 diabetes mellitus. AB - Type 1 diabetes (T1D) belongs among polygenic multifactorial autoimmune diseases. The highest risk is associated with human leucocyte antigen (HLA) class II genes, including HLA-DQA1 gene. Our aim was to investigate DNA methylation of HLA-DQA1 promoter alleles (QAP) and correlate methylation status with individual HLA-DQA1 allele expression of patients with T1D and healthy controls. DNA methylation is one of the epigenetic modifications that regulate gene expression and is known to be shaped by the environment.Sixty one patients with T1D and 39 healthy controls were involved in this study. Isolated DNA was treated with sodium bisulphite and HLA-DQA1 promoter sequence was amplified using nested PCR. After sequencing, DNA methylation of HLA-DQA1 promoter alleles was analysed. Individual mRNA HLA-DQA1 relative allele expression was assessed using two different endogenous controls (PPIA, DRA). We have found statistically significant differences in HLA-DQA1 allele 02:01 expression (PPIA normalization, Pcorr = 0.041; DRA normalization, Pcorr = 0.052) between healthy controls and patients with T1D. The complete methylation profile of the HLA-DQA1 promoter was gained with the most methylated allele DQA1*02:01 and the least methylated DQA1*05:01 in both studied groups. Methylation profile observed in patients with T1D and healthy controls was similar, and no correlation between HLA-DQA1 allele expression and DNA methylation was found. Although we have not proved significant methylation differences between the two groups, detailed DNA methylation status and its correlation with expression of each HLA-DQA1 allele in patients with T1D have been described for the first time. PMID- 26854764 TI - A high level of household physical activity compensates for lack of leisure time physical activity with regard to deficit accumulation: Results from the KORA-Age study. AB - INTRODUCTION: Aging is associated with increasing loss of physiological resilience and successive accumulation of physiological deficits. This can be measured through a frailty index which sums up symptoms, health conditions and impairments. One possible factor in preventing or delaying deficit accumulation is physical activity. The effect of leisure time physical activity on health is well investigated; however, the effect of household physical activity is less clear. The objective of this cross-sectional study was to examine the association of household physical activity with deficit accumulation while controlling for level of leisure time physical activity. METHODS: Data originates from the 2008 baseline assessment of the KORA (Cooperative Health Research in the Region of Augsburg)-Age study from Southern Germany. A frailty index of deficit accumulation (Deficit Accumulation Index, DAI) was constructed from 31 age related health deficits. Physical activity was measured with the Physical Activity Scale for the Elderly (PASE). The association of deficit accumulation and physical activity was analyzed using negative binomial regression analysis. RESULTS: The participants' (n=960, mean age 76years, 49.0% female) DAI ranged from 0.00 to 0.68. Higher levels of both types of physical activity were statistically significantly associated with less deficit accumulation. Participants in the highest household (leisure time) physical activity quartile had 29% (30%) less deficits than participants in the respective lowest quartiles. CONCLUSION: High levels of household physical activity might compensate for low levels of leisure time physical activity in the prevention of deficit accumulation. Further research efforts investigating the temporal sequence of this association are needed. PMID- 26854765 TI - Drewnowski et al. respond. PMID- 26854766 TI - Triglyceride-glucose index (TyG index) in comparison with fasting plasma glucose improved diabetes prediction in patients with normal fasting glucose: The Vascular-Metabolic CUN cohort. AB - AIMS: We evaluated the potential role of the triglyceride-glucose index (TyG index) as a predictor of diabetes in a White European cohort, and compared it to fasting plasma glucose (FPG) and triglycerides. METHODS: 4820 patients of the Vascular-Metabolic CUN cohort (VMCUN cohort) were examined and followed up for 8.84years (+/-4.39). We performed a Cox proportional hazard ratio with repeated measures analyses to assess the risk of developing type 2 diabetes across quartiles of FPG, triglycerides and the TyG index (ln[fasting triglycerides (mg/dl)*fasting plasma glucose (mg/dl)/2]), and plotted a receiver operating characteristics (ROC) curve for discrimination. RESULTS: There were 332 incident cases of type 2 diabetes involving 43,197.32person-years of follow-up. We observed a progressively increased risk of diabetes in subjects with TyG index levels of 8.31 or more. Among those with normal fasting glucose at baseline, <100mg/dl, subjects with the TyG index in the fourth quartile were 6.87 times more likely to develop diabetes (95% CI, 2.76-16.85; P for trend<0.001), as compared with the bottom quartile. The areas under the ROC curves (95% CI) were 0.75 (0.70-0.81) for TyG index, 0.66 (0.60-0.72) for FPG and 0.71 (0.65-0.77) for TG, in subjects with normal fasting glucose (p=0.017). CONCLUSIONS: Our data suggest that the TyG index is useful for the early identification of individuals at risk of type 2 diabetes. The TyG index seems to be a better predictor than FPG or triglycerides of the potential development of type 2 diabetes in normoglycemic patients. PMID- 26854767 TI - Crossing regimes of temperature dependence in animal movement. AB - A pressing challenge in ecology is to understand the effects of changing global temperatures on food web structure and dynamics. The stability of these complex ecological networks largely depends on how predator-prey interactions may respond to temperature changes. Because predators and prey rely on their velocities to catch food or avoid being eaten, understanding how temperatures may affect animal movement is central to this quest. Despite our efforts, we still lack a mechanistic understanding of how the effect of temperature on metabolic processes scales up to animal movement and beyond. Here, we merge a biomechanical approach, the Metabolic Theory of Ecology and empirical data to show that animal movement displays multiple regimes of temperature dependence. We also show that crossing these regimes has important consequences for population dynamics and stability, which depend on the parameters controlling predator-prey interactions. We argue that this dependence upon interaction parameters may help explain why experimental work on the temperature dependence of interaction strengths has so far yielded conflicting results. More importantly, these changes in the temperature dependence of animal movement can have consequences that go well beyond ecological interactions and affect, for example, animal communication, mating, sensory detection, and any behavioral modality dependent on the movement of limbs. Finally, by not taking into account the changes in temperature dependence reported here we might not be able to properly forecast the impact of global warming on ecological processes and propose appropriate mitigation action when needed. PMID- 26854768 TI - Intracranial Subdural Empyema Mimicking Chronic Subdural Hematoma. PMID- 26854769 TI - The Modified Technique of External Dacryocystorhinostomy in the Management of Complicated Nasolacrimal Duct Obstruction. AB - AIM: To evaluate the outcome of the modified technique of external dacryocystorhinostomy (EDCR) with a "U"-shaped single flap that was fixed on to the orbicularis muscle with combined silicone tube in dacriostenosis. In cases with decreased visibility because of excessive bleeding during surgery, a small sac size, and difficulty of mutual suturing between nasal mucosal and sac flaps related to distance. METHODS: This retrospective study included 118 patients with a nasolacrimal duct obstruction who underwent the modified technique of EDCR. The modified EDCR procedure envisions the creation of anastomosis of the single anterior "U"-shaped flaps suturing anterior flaps of the lacrimal sac and nasal mucosa. The sutured flap was fixed on to the orbicularis muscle. The silicone tube intubation was performed on all patients. RESULTS: The average age of the patients was 39 +/- 19.2 (9-70) years, including 94 women and 24 men. The average follow-up time was 18 +/- 4.5 (9-36) months. Total 112 eyes (94.9%) showed a patent lacrimal system to irrigation, whereas 6 eyes (5.1%) had recurrence of epiphora and not patent lacrimal system to irrigation by the end of the first surgeries. The same surgery was planned for these patients. The patent lacrimal system was achieved in 3 of these 6 eyes. The overall success rate of the surgical procedure used in this study was 97.4%. CONCLUSIONS: This modified technique of EDCR with a "U"-shaped single anterior flaps that was fixed on to the orbicularis muscle with combined silicone tube simplifies the surgical procedure and is effective in the management of nasolacrimal duct obstruction. PMID- 26854770 TI - Acquired Brown Syndrome Treated With Traction of Superior Oblique Tendon. AB - Brown syndrome is a rare strabismic disease characterized by a limited elevation in adduction of the eye. The lengthening/weakening of superior oblique muscle is the main way of surgical intervention for this disease. A 7-year-old boy was diagnosed as having acquired Brown syndrome in his right eye after injury in his face. We experienced successful release of this Brown syndrome through mere pulling outward of superior oblique tendon during surgical exploration. We briefly discuss why this manipulation of superior oblique tendon that we performed was successful. PMID- 26854771 TI - Endoscopic Versus Microscopic Approach in Pituitary Surgery. AB - The objective of this study is to compare the efficacy and complications of endoscopic and microscopic transsphenoidal surgery in the treatment of pituitary adenomas. A total of 105 follow-up cases including 60 in endoscopic surgery and 45 in microscopic surgery were treated in our hospital between January 2012 and November 2014. The endoscopic approach had a higher rate of gross tumor removal (81.7% versus 62.2%, P < 0.05) as well as a lower rate of postoperative complications (18.3% versus 35.6%, P < 0.05) than that in the microscopic group. There was no significant difference in the rates of visual improvement and cerebrospinal fluid leak between endoscopic group and microscopic group (P > 0.05). The length of the operation was longer (175 +/- 25 minutes versus 110 +/- 17 minutes, P < 0.05) but the postoperative hospital stay was significantly shorter (5.1 +/- 0.7 versus 7.8 +/- 0.8 days, P < 0.05) for the endoscopic surgery group compared with microscopic surgery group. Endoscopic approach provides a wide surgical field and broad lateral vision making easier distinction of tumor tissue. The results of this study support the safety and short-term efficacy of endoscopic pituitary surgery. PMID- 26854772 TI - Bilateral Blindness in a Patient With Temporal Arteritis After Wisdom Tooth Extraction. AB - A 78-year-old woman reported pain in her right hemiface (middle and upper portions) together with nuchal headache, some days after upper right wisdom tooth extraction. She was treated with nonsteroidal anti-inflammatory drugs by her dentist. Three weeks later, a localized headache over her right superficial temporal artery was reported, and progressive bilateral blindness appeared. A biopsy showed a late stage of temporal arteritis. All the symptoms disappeared following corticosteroid treatment, except blindness. The possible complications linking oral bacteria and extraoral infections and diseases should always be attentively considered during the clinical management of fragile patients. PMID- 26854773 TI - Serial Attacks: Contralateral Hematoma Secondary to Decompressive Craniectomy for Traumatic Brain Injury Led to Posttraumatic Cerebral Infarction. AB - A 40-year-old man suffered severe brain injury and received left side subdural hematoma evacuation with decompressive craniectomy. Intraoperative brain swelling had occurred during the surgery. Postoperative computed tomography (CT) scan was done immediately and showed a contralateral epidural hematoma resulting in herniation. Secondary hematoma evacuation was performed and found a linear fracture near a bleeding meningeal artery. 2 days later CT scan showed cerebral infarction mainly in right posterior cerebral artery distribution. Early diagnosis by postoperative CT scan or other potential ways such as intraoperative sonography is important to prompt treatments and interrupt the pathophysiological chain of the serial attacks. PMID- 26854774 TI - A Different Cartilage Graft Technique: Perichondrium-Preserved Palisade Island Graft in Tympanoplasty. AB - Various graft materials have been used since tympanoplasty technique was first described. In this study, the authors aimed to share our modified island cartilage graft technique.A total of 47 ears of 46 patients on whom tympanoplasty or tympanomastoidectomy operation was performed in our clinic because of chronic otitis media were included in the study.Mean preoperative air-bone gap of the patients was 32.25 +/- 11.85 dB and mean postoperative air-bone gap was 19.25 +/- 10.46 dB. The difference was statistically significant (P < 0.001). When all the patients were evaluated, preoperative and postoperative air conduction pure tone audiometry values were 43.38 +/- 14.74 dB and 32.61 +/- 15.62 dB, respectively. The difference was statistically significant (P < 0.001). Graft success rate in terms of perforation closure was found to be 44/47 (93.61%).Our modified island cartilage graft technique is easy to apply and its graft success rate and hearing results are good. PMID- 26854775 TI - Cone-Beam Computed Tomography Study Of Crown Dilaceration With a Talon Cusp in an Unerupted Permanent Maxillary Tooth. AB - This article describes a rare case of crown dilaceration with a talon cusp in an unerupted permanent maxillary central incisor. Our patient was a 7-year-old boy with a history of trauma to his primary maxillary teeth (#51 and 52), at 3 years of age complaining of failure of eruption of tooth #11. Periapical radiography showed incomplete formation of tooth root #11 and more superior position of tooth bud #11 relative to tooth bud #12. A cone-beam computed tomography was ordered, which revealed crown dilaceration with a talon cusp in tooth bud #11. The patient was scheduled for follow-up at 6 months. PMID- 26854776 TI - A Rare Nasopharyngeal Teratoma Arising From the Vomer. AB - Teratomas are rare germ cell neoplasms derived from the 3 germinal layers (ectoderm, mesoderm, and endoderm). Nasopharyngeal teratoma is a very rare teratoma arising anywhere from the oronasal cavity, regarded as an expanding, avity filling lesion, with a high mortality rate because of severe airway obstruction, especially in the neonatal period and make up only 2% of all teratomas. The authors present a case of an infant girl with a single, finger like, hairy teratoma arising from the vomer and protruding from the mouth with bilateral complete cleft palate, cleft lip, and cleft alveolus. Complete intraoral resection of the teratoma and cleft lip repair was conducted simultaneously. Reconstruction of the cleft palate was performed at a later stage. Recurrence occurred 9 months after surgery and extended complete surgical excision was performed after recurrence, with no recurrence observed again to date. Histopathologic examination confirmed the diagnosis of congenital mature teratoma. PMID- 26854777 TI - Atypical Carcinoid Tumor and Chondroid and Glandular Hamartoma of the Arythenoid Region. AB - Neuroendocrine tumors of the head and neck are rare. Laryngeal hamartomas are even rarer especially in adult patients. Here in a 69-year-old male patient is presented who had atypical carcinoid tumor and chondroid and glandular hamartoma of the medial mucosa of the left arythenoid. To the best of our knowledge, this is the first case presenting the association of these 2 rare lesions. PMID- 26854778 TI - Salvage Free Anterolateral Thigh Composite Flap Transfer Based on the Musculocutaneous Perforator Retrograde Blood Flow Principle. AB - An anterolateral thigh myo-adipofascial flap was used in the definitive management of a patient presented with chronic infective process associated with a large fronto-nasal defect. Unfortunately, the risk of free flap transfer failure emerged when intraoperative dissection showed absence of a reliable ipsilateral superficial temporal artery as the recipient artery. This rare incident happened at the stage whereby the anterolateral thigh flap was nearly completely raised with a distal perforator in situ. In this article, the authors presented an innovative strategy to salvage the flap by transforming the flap into a modified composite flap based on the retrograde blood flow principle. To the best of our knowledge, this is the first report of using such a technique in reconstructive microsurgery. This successful salvage strategy has clinical application and could potentially minimize free flap transfer failure. PMID- 26854779 TI - The Deltopectoral Flap Revisited: The Internal Mammary Artery Perforator Flap. AB - Pharyngo-esophageal and tracheostomal defects pose a challenge in head and neck reconstruction whenever microanastomosis is extremely difficult in hostile neck that is previously dissected and irradiated. The deltopectoral (DP) flap was initially described as a pedicled flap for such reconstruction with acceptable postoperative results. A major drawback is still that the DP flap is based on 3 perforator vessels leading to a decreased arc of rotation. The DP flap also left contour deformities in the donor site. The internal mammary artery perforator flap was described as a refinement of the deltopectoral flap. It is a pedicled fasciocutaneous flap based on a single perforator, with comparable and reliable blood supply compared with the DP flap, giving it the benefit of having a wide arc of rotation. It is both thin and pliable, with good skin color match and texture. The donor site can be closed primarily with no esthetic deformity and minimal morbidity. The procedure is relatively simple and does not require microvascular expertise. In this report, the authors describe a patient in whom bilateral internal mammary artery perforator flaps were used for subtotal pharyngo-esophageal reconstruction and neck resurfacing. The flaps healed uneventfully bilaterally with no postoperative complications. PMID- 26854780 TI - A Comparison of the Effect Between Coronoid Process Graft and Costochondral Graft in the Reconstruction of Temporomandibular Joint. AB - PURPOSE: Bone graft to reconstruct the temporomandibular joint for ankylosis patient is effective. This study used three-dimensional measurement to evaluate the effect between free coronoid process graft (CPG) and costochondral graft (CCG) in the temporomandibular joint reconstruction. METHODS: Patients treated with CPG or CCG from 2011 to 2014 were included in the study. Postoperative computed tomography scan data within 1 week and during at least 6 months follow up after operation were imported into Proplan CMF 1.4 software (Materialize, Belgium) for three-dimensional reconstruction and measurement. Heights of the mandibular ramus were measured and compared between the 2 groups. Maximum mouth opening and occlusion were also evaluated and compared before and after operation. RESULTS: Ten patients with 15 reconstructed joints were included in the study. In the CPG group, the decrease of ramus height was 5.4 mm after a mean follow-up period of 16.8 months (ranged from 6 to 22 months), whereas in the CCG group, it was 2.4 mm after a mean follow-up period of 14.4 months (ranged from 6 to 30 months). There was significant difference of ramus height decrease between the CPG group and the CCG group (P < 0.05). Maximum mouth opening was significantly increased after operation than before in both groups (P < 0.05). Open bite happened in 4 of 5 patients in the CPG group, and 1 of 5 patients in the CCG group. CONCLUSIONS: CPG has higher frequency of a malocclusion secondary to resorption than CCG for the ramus reconstruction. PMID- 26854781 TI - Ischemic Necrosis of Upper Lip, and All Fingers and Toes After Norepinephrine Use. AB - A 68-year-old woman with necrosis of total finger, toe, and upper lip was requested by department of internal medicine. She was diagnosed with septic shock and treated with norepinephrine 10 days ago. Norepinephrine is an often-used medicine for normalizing blood pressure in septic shock patients. Norepinephrine stimulates adrenergic receptors, causing vasoconstriction and the rise of blood pressure. These peripheral vasoconstrictions sometimes lead to ischemic changes in end organs. In this case report, the authors describe ischemic necrosis of the upper lip and all fingers and toes after norepinephrine use in a patient in the intensive care unit. PMID- 26854783 TI - Dentures as Learning Materials for Maxillomandibular Fixation by Erich Arch Bars. AB - Maxillomandibular fixation with Erich arch bars is an economic method for handling mandibular fractures. Unfortunately, this method has some disadvantages, such as long operating time, periodontal trauma, and risk of puncture injury to the operator. To overcome these disadvantages, we propose teaching the pits and pearls of maxillomandibular fixation with Erich arch bars to trainees using dentures of a patient. Experiencing the method on dentures will shorten the learning curve. PMID- 26854784 TI - Assessment of Stability of Craniofacial Implants by Resonant Frequency Analysis. AB - Implant stability is a principal precondition for the success of implant therapy. Extraoral implants (EO) are mainly used for anchoring of maxillofacial epithesis. However, assessment of implant stability is mostly based on principles derived from oral implants. The aim of this study was to investigate clinical stability of EO craniofacial disk implants (single, double, and triple) by resonance frequency analysis at different stages of the bone's healing. Twenty patients with orbital (11), nasal (5), and auricular (4) defects with 50 EO implants placed for epithesis anchorage were included. Implant stability was measured 3 times; after implant placement, at 3 months and at least after 6 months. A significant increase in implant stability values was noted between all of the measurements, except for triple-disk implants between third and sixth months, and screw implants between 0 and third months. Disk implants showed lower implant stability quotient (ISQ) values compared with screw implants. Triple-disk implants showed better stability compared with single and double-disk implants. Based on resonance frequency analysis values, disk implants could be safely loaded when their ISQ values are 38 (single disks), 47 (double disks), and 48 (triple disks). According to resonance frequency analysis, disk implant stability increased over time, which showed good osseointegration and increasing mineralization. Although EO screw implants showed higher ISQ values than disk implants, disk-type implants can be safely loaded even if lower values of stability are measured. PMID- 26854785 TI - Surface Reconstruction and Optimization of Cerebral Cortex for Application Use. AB - For the purposes of virtual surgery, medical education, medical communication, and realistic surface models of anatomic structures are required. In the most involved method, surface models can be made using segmentation and three dimensional reconstruction procedures. Such models, however, are computationally expensive, and can be difficult to use. Therefore, optimization is often performed manually, but this is a time-consuming job that requires considerable artistic talent. In this article, the authors describe a method that uses Maya and ZBrush to construct optimized surface models of anatomic structures. The authors take 235 anatomic images generated from a cadaver, and perform segmentation and surface reconstruction using Photoshop and Mimics. Reconstructed surface models of the cerebral cortex are then optimized and divided by a morphing technique in Maya and ZBrush for use in medical applications. The optimized surface models do not require significant storage space, and are easily manufactured and modified. The resulting surface models can be displayed off-line and on-line in real time, as well as on smart phones. Using commercial software with the specialized functions described in this study, it is expected that the efficiencies produced by the proposed method will enable researchers to conveniently create surface models from serially sectioned images such as computed tomographs and magnetic resonance images. The surface models created in this research will also have widespread applications in both medical education and communication. PMID- 26854786 TI - Tracking and Increasing Viability of Topically Injected Fibroblasts Suspended in Hyaluronic Acid Filler. AB - A new injectable tissue-engineered soft tissue consisting of a mixture of hyaluronic acid (HA) filler and cultured human fibroblasts have been developed by the authors. To establish this method as a standard treatment, a further study was required to determine whether the injected fibroblasts could stay at the injected place or move to other sites. In addition, effective strategies were needed to increase viability of the injected fibroblasts. The purpose of this study was to track the injected fibroblasts and to determine the effect of adding prostaglandin E1 (PGE1) or vitamin C on the viability of fibroblasts.Human fibroblasts labeled with fluorescence dye were suspended in HA filler and injected into 4 sites on the back of nude mice. The injected bioimplants consisted of one of the 4 followings: HA filler without cells (HA group), fibroblasts suspended in HA filler (HA + FB group), PGE1-supplemented fibroblasts in HA filler (HA + FB + PGE1 group), and vitamin C-supplemented fibroblasts in HA filler (HA + FB + VC group). At 4 weeks after injection, locations and intensities of the fluorescence signals were evaluated using a live imaging system.The fluorescence signals of the fibroblast-containing groups were visible only at the injected sites without dispersing to other sites. The HA +FB + PGE1 group showed a significantly higher fluorescence signal than the HA + FB and the HA + FB +VC groups (P < 0.05, each). There was no statistical difference between the HA + FB and HA + FB +VC groups (P = 0.69).The results of the current study collectively suggest that injected fibroblasts suspended in HA filler stay at the injected place without moving to other sites. In addition, PGE1 treatment may increase the remaining rhodamine B isothiocynanate dye at the injected site of the human dermal fibroblasts. PMID- 26854787 TI - Solution-Processable Carbon Nanoelectrodes for Single-Molecule Investigations. AB - Here we present a solution-based assembly method for producing molecular transport junctions employing metallic single-walled carbon nanotubes as nanoelectrodes. The molecular junction conductance of a series of oligophenyls was successfully measured, highlighting the potential of an all-carbon based approach for the fabrication of solution-processable single-molecule junctions for molecular electronics. PMID- 26854788 TI - Continuous Measurements of Dissolved Ne, Ar, Kr, and Xe Ratios with a Field Deployable Gas Equilibration Mass Spectrometer. AB - Noble gases dissolved in natural waters are useful tracers for quantifying physical processes. Here, we describe a field-deployable gas equilibration mass spectrometer (GEMS) that provides continuous, real-time measurements of Ne, Ar, Kr, and Xe mole ratios in natural waters. Gas is equilibrated with a membrane contactor cartridge and measured with a quadrupole mass spectrometer, after in line purification with reactive metal alloy getters. We use an electron energy of 35 V for Ne to eliminate isobaric interferences, and a higher electron energy for the other gases to improve sensitivity. The precision is 0.7% or better and 1.0% or better for all mole ratios when the instrument is installed in a temperature controlled environment and a variable-temperature environment, respectively. In the lab, the accuracy is 0.9% or better for all gas ratios using air as the only calibration standard. In the field (and/or at greater levels of disequilbrium), the accuracy is 0.7% or better for Ne/Kr, Ne/Ar, and Ar/Kr, and 2.5% or better for Ne/Xe, Ar/Xe, and Kr/Xe using air as the only calibration standard. The field accuracy improves to 0.6% or better for Ne/Xe, Ar/Xe, and Kr/Xe when the data is calibrated using discrete water samples run on a laboratory-based mass spectrometer. The e-folding response time is 90-410 s. This instrument enables the collection of a large number of continuous, high-precision and accuracy noble gas measurements at substantially reduced cost and labor compared to traditional methods. PMID- 26854789 TI - Basketball Players' Dynamic Performance Across Competition Levels. AB - Bullock, GS, Arnold, TW, Plisky, PJ, and Butler, RJ. Basketball players' dynamic performance across competition levels. J Strength Cond Res 32(12): 3537-3542, 2018-Dynamic balance is an integral component in screening lower extremity injury risk. Previous research has identified the need to create sport- and competition level-specific dynamic balance injury cut points. The purpose of this study was to determine if dynamic balance differences exist, using the Lower Quarter Y Balance Test (YBT-LQ), across varying competition levels (middle school, high school, college, and professional), in basketball players. Subjects were participating at the middle school (MS; n = 88), high school (HS; n = 105), college (COL; n = 46), and professional levels (PRO; n = 41). Statistical analysis was completed with a series of analysis of variance tests. Tukey post hoc tests were used to identify specific group-to-group differences if statistical significance (p <= 0.05) was observed. Effect size indices (ESI) were also calculated to provide an estimate of the clinical relevance. In the anterior reach, HS basketball players performed statistically better than the MS and COL (p < 0.01, ESI = 0.58) athletes, and all these groups performed better than the PRO basketball players (p < 0.01, ESI = 1.72). For the posteromedial, posterolateral reach directions and the composite score, the HS, COL, and PRO basketball players were not significantly different from each other; however, the HS group did reach further than the MS group (p < 0.01-0.02, ESI = 0.40-0.55). The PRO basketball players exhibited a lower asymmetrical total score compared with MS, HS, and COL players (p < 0.01-0.02, ESI = 0.52-0.68). Different competition levels displayed varying dynamic balance strategies. Creating basketball competition levels normative values for dynamic balance could help define injury risk cut points. PMID- 26854790 TI - Long-term Safety of Living Kidney Donation in an Emerging Economy. AB - BACKGROUND: Long-term follow-up and management of donors was undertaken in a specialist kidney transplant unit in Pakistan to identify risk and prevent adverse outcomes in living related kidney donors. METHODS: In an observation cohort study between 1985 and 2012, 3748 donors were offered free medical follow up and treatment 6 to 12 months after donation and annually thereafter. Each visit included history, physical examination, blood tests for renal, lipid, glucose profiles, and 24-hour urine for proteinuria and creatinine clearance. Preventive intervention was undertaken for new onset clinical conditions. Donor outcomes were compared with 90 nondonor healthy siblings matched for age, sex, and body mass index. RESULTS: Of the 3748 donors, 2696 (72%) were in regular yearly follow-up for up to 27 years (median, 5.6; interquartile range, 7.9). Eleven (0.4%) died 4 to 22 years after donation with all-cause mortality of 4.0/10 000 person years. Six (0.2%) developed end-stage renal disease 5 to 17 years after donation, (2.7/10 000 person years). Proteinuria greater than 1000 mg/24 hours developed in 28 patients (1%), hypertension in 371 patients (13.7%), and diabetes in 95 patients (3.6%). Therapeutic intervention-controlled protein was less than 1000 mg/24 hours, blood pressure was below 140/90 mm Hg, and glycemic control in 85% up to 15 years after onset. Creatinine clearance fell from 109.8 +/- 22.3 mL/min per 1.73 m predonation to 78 +/- 17 at 1 year, 84 +/- 19 at 5 years, and 70 +/- 20 at 25 years. Comparison of 90 nondonor sibling and donor pairs showed significantly higher fasting glucose and hypertension in nondonors. CONCLUSIONS: Long-term follow-up of donors has demonstrated end-stage renal disease in 0.6% at 25 years. Regular follow-up identified new onset of disease and allowed interventions that may have prevented adverse outcomes. PMID- 26854792 TI - Correction: GIS-based multi-criteria analysis for Arabica coffee expansion in Rwanda. PMID- 26854791 TI - Technological, sensory and microbiological impacts of sodium reduction in frankfurters. AB - Initially, meat emulsions were studied in a model system to optimize phosphate and potassium chloride concentrations. In the second step, frankfurters containing 1.00%, 1.30% and 1.75% sodium chloride (NaCl) were processed and their stability was monitored over 56 days. In the emulsion tests, the best levels in relation to shear force found in model system were 0.85% and 0.25% of potassium chloride and phosphate, respectively. In the second step, treatments with 1.30% and 1.75% NaCl performed better in most of the analysis, particularly the sensory analysis. Consumers could identify the levels of salt, but this was not the factor that determined the overall acceptability. In some technological parameters, frankfurters with 1.30% NaCl were better than those with 1.75%. This represents a reduction of approximately 25% sodium chloride, or 18% reduction in sodium (916 mg/100g to 750 mg/100g), and it appears to be feasible from a technological, microbiological and sensory point of view. PMID- 26854793 TI - Forecasting the future pain in hip OA: can we rely on pain trajectories? PMID- 26854794 TI - Defining hip pain trajectories in early symptomatic hip osteoarthritis--5 year results from a nationwide prospective cohort study (CHECK). AB - OBJECTIVE: To define distinct hip pain trajectories in individuals with early symptomatic hip osteoarthritis (OA) and to determine risk factors for these pain trajectories. METHOD: Data were obtained from the nationwide prospective Cohort Hip and Cohort Knee (CHECK) study. Participants with hip pain or stiffness and a completed 5-year follow-up were included. Baseline demographic, anamnestic, physical examination characteristics were assessed. Outcome was annually assessed by the Numeric Rating Scale (NRS) for pain. Pain trajectories were retrieved by latent class growth analysis (LCGA). Multinomial logistic regression was used to calculate risk ratios. RESULTS: 545 participants were included. Four distinct pain trajectories were uncovered by LCGA. We found significant differences in baseline characteristics, including body mass index (BMI); symptom severity; pain coping strategies and in criteria for clinical hip OA (American College of Rheumatology (ACR)). Lower education, higher activity limitation scores, frequent use of pain transformation as coping strategy and painful internal hip rotation were more often associated with trajectories characterized by more severe pain. No association was found for baseline radiographic features. CONCLUSION: We defined four distinct pain trajectories over 5 years follow-up in individuals with early symptomatic hip OA, suggesting there are differences in symptomatic progression of hip OA. Baseline radiographic severity was not associated with the pain trajectories. Future research should be aimed at measuring symptomatic progression of hip OA with even more frequent symptom assessment. PMID- 26854796 TI - Serological screening for celiac disease in a northern Italian child and adolescent population after the onset of type 1 diabetes: a retrospective longitudinal study of a 7-year period. AB - AIM: To evaluate the temporal trend and extent of screening for celiac disease in an Italian pediatric population of incident type 1 diabetes in the period 2006 2011, providing information on adherence to guidelines in primary care. METHODS: Using the Lombardy region's administrative database, 1-17-year-old children and adolescents diagnosed with type 1 diabetes during the 2006-2011 period were identified. Among these patients, the number screened for celiac disease was calculated on the basis of specific antibodies. RESULTS: Of the 1563 children and adolescents receiving a diagnosis of type 1 diabetes during the observational period, 53% were tested for celiac disease compared with 12% of individuals without diabetes. The extent to which screening was performed increased two-fold from the 2006-2008 to the 2009-2011 period (P<0.0001). Among the screened population, 1.8 of the non-type 1 diabetes population and 9.4% of the new cases of type 1 diabetes received a diagnosis of celiac disease (90% after type1 diabetes diagnosis and 10% before). Being female and less than 4 years old were factors associated with an increased risk of receiving both diagnoses. CONCLUSION: In conclusion, to the best of our knowledge, this is the first report in which celiac disease screening is measured in a type 1 diabetes population from the time of diagnosis up to at least 12 months afterwards. The results provide evidence that, although the rate of screening increased over time, nearly half of children with type 1 diabetes were not screened after diagnosis during the observed period, suggesting scarce adherence to guidelines in primary care. PMID- 26854795 TI - Combination of preoperative platelet/lymphocyte and neutrophil/lymphocyte rates and tumor-related factors to predict lymph node metastasis in patients with gastric cancer. AB - OBJECTIVE: Lymph node (LN) metastasis is widely accepted as a poor prognosis indicator in patients with gastric cancer. An accurate preoperative prediction of LN status is of crucial importance for the planning treatment. The aim of the present study was to assess the predictive value of the preoperative platelet/lymphocyte (PLR) and neutrophil/lymphocyte rates (NLR) on the LN metastasis in gastric cancer patients and to develop a new preoperative score system to predict LN metastasis. PATIENTS AND METHODS: A total of 492 operable patients with gastric cancer were enrolled in our study. The clinical utility of the PLR and NLR was evaluated by receiver operating characteristic (ROC) curves. The logistic analysis was used to identify the independent parameters associated with LN metastasis. Then, a score system including those independent parameters that can be detected preoperatively was established, which was also tested by an ROC curve. RESULTS: The ideal cutoff values for predicting LN metastasis were 1.59 for NLR and 155.67 for PLR according to the ROC curve. Multivariate analyses showed that both PLR and NLR are significantly associated with LN metastasis independent of depth of invasion, lymphatic invasion, macroscopic type, and tumor size. The area under the ROC curve of the score system was 0.830 (95% confidence interval 0.782-0.878), showing a reliable ability to evaluate the status of nodal involvement. CONCLUSION: Preoperative PLR and NLR are useful biomarkers to predict LN metastasis and the score system in our study may serve as a reliable instrument to predict LN metastasis in gastric cancer patients. PMID- 26854797 TI - Capsule endoscopy is useful diagnostic tool for diagnosing Meckel's diverticulum. AB - OBJECTIVE: Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract. Although a majority of patients remain asymptomatic, complications may occur in a subset of patients. MD is a rare cause of gastrointestinal bleeding (GIB) in adults. We aimed to clarify the possible role of capsule endoscopy (CE) in the identification of Meckel's diverticulum. PATIENTS AND METHODS: From October 2004 to December 2010, 157 CEs were performed (83 male individuals, mean age 51+/-20 years; range 3-83 years) for obscure GIB. Before CE, all patients underwent nonconclusive upper and lower endoscopy at least two times and barium follow-through. RESULTS: CE identified the source of bleeding in 70/157 patients (44.6%). MD was diagnosed in 13/70 (18.6%) patients (11 male individuals, mean age 35+/-20 years, range, 3-69 years) after CE. Nine patients presented with obscure overt and four with obscure occult bleeding. The mean duration of obscure GIB history was 13 months (range 1-72 months). The mean hemoglobin concentration at the time of the procedure was 115+/-12 g/l. The findings of MD on CE were double lumen sign (13/13), visible blood (7/13), and diaphragm sign (6/13). All patients were operated upon, and MD histologically verified in 11. In two patients CE was false-positive and in two patients, false negative. Capsule endoscopy had a positive predictive value of 84.6% for the diagnosis of MD. CONCLUSION: MD should be considered in the differential diagnosis of obscure GIB in adults. CE is an effective and promising modality for diagnosing MD in patients with obscure GIB. PMID- 26854798 TI - Chemerin: a new biomarker to predict postendoscopic retrograde cholangiopancreatography pancreatitis. AB - INTRODUCTION: Individuals with increased visceral adiposity are considered to be more sensitive and more prone to severe acute pancreatitis because of the inflammatory microenvironment they have. We hypothesized that insulin resistance, adipokines, and proinflammatory cytokines that markedly affect the course of pancreatitis can contribute toward development of postendoscopic retrograde cholangiopancreatography (post-ERCP) pancreatitis (PEP) and aimed to investigate the association between PEP risk and preprocedural serum vaspin, chemerin, tumor necrosis factor alpha, interleukin-6 (IL-6) levels, and homeostasis model assessment of insulin resistance. PATIENTS AND METHODS: Eighty-two patients with a diagnosis of choledocholithiasis and 30 controls were enrolled. Preprocedural chemerin, vaspin, IL-6, and well-known PEP risk factors were compared between PEP and non-PEP groups. RESULTS: The mean age of the patients was 56.3+/-14.4 years; 52 patients were women. Adipocytokine levels, BMIs, and waist circumferences of the patient group were found to be higher than those of the controls. Total cannulation success and the mean procedure time were 82.9% and 28.7+/-8.8 min, respectively. PEP developed in 12 (14.6%) patients. Chemerin levels in the PEP group were higher than those in the non-PEP group (580.2+/-172.5 vs. 392.2+/ 168.2 ng/ml, P<0.01). Insulin resistance was higher in the PEP group than the non PEP group (P=0.001), but there was no significant difference between PEP and non PEP groups in terms of preprocedural vaspin, tumor necrosis factor alpha, IL-6, and C-reactive protein levels. According to logistic regression analysis, increased chemerin levels, homeostasis model assessment of insulin resistance 2.5 or greater, and pancreatic duct cannulation were found to be independent risk factors for PEP [odds ratio (OR)=1.006, P=0.006; OR=4.57, P=0.05; OR=6.54, P=0.02]. CONCLUSION: Elevated serum chemerin levels and insulin resistance are independent risk factors of PEP development. PMID- 26854799 TI - Low 25-Hydroxyvitamin D Level Is Associated with Peripheral Arterial Disease in Type 2 Diabetes Patients. AB - BACKGROUND AND AIMS: Patients with type 2 diabetes have an increased risk of atherosclerosis and vascular disease. Vitamin D deficiency is associated with vascular disease and is prevalent in diabetes patients. We undertook this study to determine the association between 25-hydroxyvitamin D (25[OH]D) levels and prevalence of peripheral arterial disease (PAD) in type 2 diabetes patients. METHODS: A total of 1028 type 2 diabetes patients were recruited at Nanjing Medical University Affiliated Nanjing Hospital from November 2011 to October 2013. PAD was defined as an ankle-brachial index (ABI) < 0.9. Cardiovascular risk factors (blood pressure, HbA1c, lipid profile), comorbidities, carotid intima media thickness (IMT) and 25(OH)D were assessed. RESULTS: Overall prevalence of PAD and of decreased 25(OH)D (<30 ng/mL) were 20.1% (207/1028) and 54.6% (561/1028), respectively. PAD prevalence was higher in participants with decreased (23.9%) than in those with normal (15.6%) 25(OH)D (>=30 ng/mL, p <0.01). Decreased 25(OH)D was associated with increased risk of PAD (odds ratio [OR], 1.69, 95% CI: 1.17-2.44, p <0.001) and PAD was significantly more likely to occur in participants >=65 years of age (OR, 2.56, 95% CI: 1.51 -4.48, vs. 1.21, 95% CI: 0.80-1.83, p-interaction = 0.027). After adjusting for known cardiovascular risk factors and potential confounding variables, the association of decreased 25(OH)D and PAD remained significant in patients <65 years of age (OR, 1.55; 95% CI: 1.14-2.12, p = 0.006). CONCLUSIONS: Low serum 25(OH)D levels were significantly associated with a higher prevalence of PAD in type 2 diabetes patients <65 years of age. It may increase the risk of PAD independent of other known cardiovascular risk factors. PMID- 26854800 TI - Noninvasive assessments of oxygen delivery from the microcirculation to skin in hypothermia-treated asphyxiated newborn infants. AB - BACKGROUND: Therapeutic hypothermia (TH) has become standard treatment for severe and moderate hypoxic-ischemic neonatal encephalopathy (HIE). Our group has developed an optically based, noninvasive concept of assessing the capacity for oxygen delivery from the microcirculation to the cells of a tissue under investigation. The hypothesis was that mechanisms of reduced oxygen delivery due to reduced metabolism in cooled asphyxiated neonates could be characterized with this concept. METHODS: The skin of 28 asphyxiated newborn infants was studied on days 1 and 3 during TH and on day 4 following rewarming with laser Doppler perfusion measurements (LDPM), computer-assisted video microscopy (CAVM), and diffuse reflectance spectroscopy (DRS). Twenty-five healthy neonates served as a control group. RESULTS: The LDPM decreased during cooling (P < 0.01). Functional capillary density was higher both during and following TH compared with control infants (P < 0.01). Capillary flow velocities were reduced during TH (P < 0.05). The heterogeneity of the flow velocities was larger in the HIE infants than in the control infants. Tissue oxygen extraction was higher during TH (P < 0.01). CONCLUSION: This study indicates that assessments of skin microvascular density, capillary flow velocity, and oxygen extraction can be used to characterize reduced oxygen delivery to cells during TH. PMID- 26854801 TI - Glucose intolerance develops prior to increased adiposity and accelerated cessation of estrous cyclicity in female growth-restricted rats. AB - BACKGROUND: The incidence of metabolic disease increases in early menopause. Low birth weight influences the age at menopause. Thus, this study tested the hypothesis that intrauterine growth restriction programs early reproductive aging and impaired glucose homeostasis in female rats. METHODS: Estrous cyclicity, body composition, and glucose homeostasis were determined in female control and growth restricted rats at 6 and 12 mo of age; sex steroids at 12 mo. RESULTS: Glucose intolerance was present at 6 mo of age prior to cessation of estrous cyclicity and increased adiposity in female growth-restricted rats. However, female growth restricted rats exhibited persistent estrus and a significant increase in adiposity, fasting glucose, and testosterone at 12 mo of age (P < 0.05). Insulin release in response to a glucose challenge was blunted in conjunction with a reduction in protein expression of pancreatic glucose transporter type 2 and estrogen receptor-alpha at 12 mo of age in female growth-restricted rats (P < 0.05). CONCLUSION: This study demonstrated that slow fetal growth programmed glucose intolerance that developed prior to early estrous acyclicity; yet, fasting glucose levels were elevated in conjunction with increased adiposity, accelerated cessation of estrous cyclicity and a shift toward testosterone excess at 12 mo of age in female growth-restricted rats. PMID- 26854802 TI - Mechanistic Role of Li+ Dissociation Level in Aprotic Li-O2 Battery. AB - The kinetics and thermodynamics of oxygen reduction reactions (ORR) in aprotic Li electrolyte were shown to be highly dependent on the surrounding chemical environment and electrochemical conditions. Numerous reports have demonstrated the importance of high donor number (DN) solvents for enhanced ORR, and attributed this phenomenon to the stabilizing interactions between the reduced oxygen species and the solvent molecules. We focus herein on the often overlooked effect of the Li salt used in the electrolyte solution. We show that the level of dissociation of the salt used plays a significant role in the ORR, even as important as the effect of the solvent DN. We clearly show that the salt used dictates the kinetics and thermodynamic of the ORR, and also enables control of the reduced Li2O2 morphology. By optimizing the salt composition, we have managed to demonstrate a superior ORR behavior in diglyme solutions, even when compared to the high DN DMSO solutions. Our work paves the way for optimization of various solvents with reasonable anodic and cathodic stabilities, which have so far been overlooked due to their relatively low DN. PMID- 26854803 TI - Dopamine neurons share common response function for reward prediction error. AB - Dopamine neurons are thought to signal reward prediction error, or the difference between actual and predicted reward. How dopamine neurons jointly encode this information, however, remains unclear. One possibility is that different neurons specialize in different aspects of prediction error; another is that each neuron calculates prediction error in the same way. We recorded from optogenetically identified dopamine neurons in the lateral ventral tegmental area (VTA) while mice performed classical conditioning tasks. Our tasks allowed us to determine the full prediction error functions of dopamine neurons and compare them to each other. We found marked homogeneity among individual dopamine neurons: their responses to both unexpected and expected rewards followed the same function, just scaled up or down. As a result, we were able to describe both individual and population responses using just two parameters. Such uniformity ensures robust information coding, allowing each dopamine neuron to contribute fully to the prediction error signal. PMID- 26854804 TI - Metabotropic NMDA receptor signaling couples Src family kinases to pannexin-1 during excitotoxicity. AB - Overactivation of neuronal N-methyl-D-aspartate receptors (NMDARs) causes excitotoxicity and is necessary for neuronal death. In the classical view, these ligand-gated Ca(2+)-permeable ionotropic receptors require co-agonists and membrane depolarization for activation. We report that NMDARs signal during ligand binding without activation of their ion conduction pore. Pharmacological pore block with MK-801, physiological pore block with Mg(2+) or a Ca(2+) impermeable NMDAR variant prevented NMDAR currents, but did not block excitotoxic dendritic blebbing and secondary currents induced by exogenous NMDA. NMDARs, Src kinase and Panx1 form a signaling complex, and activation of Panx1 required phosphorylation at Y308. Disruption of this NMDAR-Src-Panx1 signaling complex in vitro or in vivo by administration of an interfering peptide either before or 2 h after ischemia or stroke was neuroprotective. Our observations provide insights into a new signaling modality of NMDARs that has broad-reaching implications for brain physiology and pathology. PMID- 26854806 TI - Comparison of the effect of semen from HIV-infected and uninfected men on CD4+ T cell infection. AB - OBJECTIVES: Semen composition is influenced by HIV-1 infection, yet the impact of semen components on HIV infection of primary target cells has only been studied in samples from HIV-uninfected donors. DESIGN: We compared the effect of seminal plasma (SP) from chronically HIV-infected (SP+) versus uninfected donors (SP-) on HIV-1 infection of peripheral blood mononuclear cells (PBMCs) and CD4 T cells. METHODS: Primary cells were infected with HIV-1 in the presence of SP+ or SP- and analyzed for infection level, metabolic activity, HIV receptor expression, proliferation and activation. SP+ and SP- were compared for infection-enhancing peptides, cytokines and prostaglandin E2 levels. RESULTS: SP- efficiently enhanced HIV-1 R5 infection of CD4 T cells, whereas SP+ enhancing activity was significantly reduced. RANTES (CCL5) concentrations were elevated in SP+ relative to SP-, whereas the concentrations of infectivity-enhancing peptides [semen derived enhancer of viral infection (SEVI), SEM1, SEM2] were similar. CCR5 membrane expression levels were reduced on CD4 T cells shortly postexposure to SP+ compared with SP- and correlated to R5-tropic HIV-1 infection levels, and CCR5 ligands' concentrations in semen. SP+ and SP- displayed similar enhancing activity on PBMC infection by X4-tropic HIV-1. Addition/depletion of RANTES (regulated on activation, normal T-cell expressed and secreted) from SPs modulated their effect on PBMC infection by R5-tropic HIV-1. CONCLUSION: Semen from HIV-infected donors exhibits a significantly reduced enhancing potential on CD4 T-cell infection by R5-tropic HIV-1 when compared with semen from uninfected donors. Our data indicate that elevated seminal concentrations of RANTES in HIV infected men can influence the ability of semen to enhance infection. PMID- 26854807 TI - Rate and predictors of progression in elite and viremic HIV-1 controllers. AB - BACKGROUND: The proportion of HIV controllers developing virologic, immunological or clinical progression and the baseline predictors of these outcomes have not been assessed in large cohorts. METHODS: A multicenter cohort of HIV controllers was followed from baseline (the first of the three HIV-1 RNA levels < 50 in elite controller or from 50 to 2000 copies/ml in viremic controllers) up to August 2011, to the development of a progression event (loss of viral load control, CD4 decline, AIDS or death) or to the censoring date (lost to follow-up or initiation of antiretroviral therapy). Predictive models of progression at baseline and a risk score for the combined HIV-1 progression end point were calculated. RESULTS: Four hundred and seventy-five HIV-1 controllers of whom 204 (42.9%) were elite controller with 2972 person-years of follow-up were identified. One hundred and forty-one (29.7%) patients lost viral load control. CD4 cell count declined in 229 (48.2%) patients. Thirteen patients developed an AIDS event and four died. Two hundred and eighty-seven (60.4%) developed a combined HIV-1 progression. Baseline predictors for the progression end points and for elite and viremic controller patients were very similar: risk for HIV-1 acquisition, baseline calendar year, CD4 nadir, viral load before baseline and hepatitis C virus coinfection. The probability of a combined HIV-1 progression at 5 years was 70% for elite controllers with the highest score compared with 13% for those with the lowest. CONCLUSION: HIV-1 disease progression in elite and viremic controllers is frequent. We propose a baseline clinical score to easily classify these patients according to risk of progression. This score could be instrumental for taking clinical decisions and performing pathogenic studies. PMID- 26854808 TI - Maraviroc and reverse transcriptase inhibitors combinations as potential preexposure prophylaxis candidates. AB - OBJECTIVE: Receptive anal intercourse in both men and women is associated with the highest probability for sexual acquisition of HIV infection. As part of a program to develop an effective prevention strategy, we performed an ex-vivo preclinical evaluation to determine the efficacy of multiple double combinations of maraviroc (MVC) and reverse transcriptase inhibitors (RTIs). DESIGN: The entry inhibitor, MVC, a nucleotide RTI, tenofovir and two non-nucleoside RTIs, UC781 and TMC120 (dapivirine, DPV), were used in double, combinations against a panel of CCR5-using clade B and clade C HIV-1 isolates and against MVC-escape variants. A gel-formulated version of MVC-DPV combination was also tested. METHODS: Indicator cells, cocultures of immature dendritic cells with CD4T cells, and colorectal tissue explants were used to assess antiviral activity of drug combinations. RESULTS: All dual MVC-RTI combinations tested inhibited MVC sensitive and resistant isolates in cellular and colorectal explants models. All the combinations were positive with no reduction in the activity of MVC. In tissue explants, the combinations against all viral isolates tested produced an increase in the activity of MVC. An initial gel-formulation of MVC-DPV combination showed greater and prolonged antiviral activity of MVC in mucosal tissue explants. CONCLUSION: This study demonstrates that combinations based on antiretroviral drugs inhibiting HIV transmission at viral entry and reverse transcription have potential as prevention strategies against colorectal transmission of HIV-1 including MVC-resistant isolates. Preclinical evaluation with colorectal tissue explants indicates that a gel-formulation of MVC-DPV is an effective candidate colorectal microbicide. PMID- 26854809 TI - Risk of cancer in children exposed to didanosine in utero. AB - BACKGROUND: Evaluation of long-term tolerance to antiretroviral exposure during pregnancy is required. An increased risk of cancer has been suggested in children exposed in utero to didanosine. METHODS: Updated evaluation of cancer incidence in uninfected children exposed to nucleos(t)ide reverse transcriptase inhibitors (NRTIs) in the French perinatal study of children born to HIV+ mothers, by cross checking with the National Cancer Registry. Associations between cancer risk and exposure to NRTIs were evaluated by univariate survival analysis and Cox proportional hazard models. Standardized incidence ratios (SIR) were used for comparison with the general population. RESULTS: A total of 21 cancers were identified in 15 163 children (median age: 9.9 years [interquartile range (IQR): 5.8-14.2]) exposed to at least one NRTI in utero, between 1990 and 2014. Five children were exposed to zidovudine monotherapy, and 16 to various combinations, seven including didanosine. Didanosine accounted for only 10% of prescriptions but was associated with one-third of cancers. In a multivariate analysis, didanosine exposure was significantly associated with higher risk [hazard ratio = 3.0 (0.9-9.8)]. The risk was specifically linked with first-trimester exposure [hazard ratio = 5.5 (2.1-14.4)]. Overall, the total number of cases was not significantly different from that expected for the general population [SIR = 0.8 (0.47-1.24)], but was twice that expected after didanosine exposure [SIR = 2.5 (1.01-5.19)]. CONCLUSION: There are strong arguments to suggest that didanosine displays transplacental oncogenicity. Although not extrapolable to other NRTIs, they stress the need for comprehensive evaluation of the transplacental genotoxicity of this antiretroviral class. PMID- 26854810 TI - Once-daily maraviroc versus tenofovir/emtricitabine each combined with darunavir/ritonavir for initial HIV-1 treatment. AB - OBJECTIVE: The aim of this study was to evaluate the efficacy of maraviroc along with darunavir/ritonavir, all once daily, for the treatment of antiretroviral naive HIV-1 infected individuals. DESIGN: MODERN was a multicentre, double-blind, noninferiority, phase III study in HIV-1 infected, antiretroviral-naive adults with plasma HIV-1 RNA at least 1000 copies/ml and no evidence of reduced susceptibility to study drugs. METHODS: At screening, participants were randomized 1 : 1 to undergo either genotypic or phenotypic tropism testing. Participants with CCR5-tropic HIV-1 were randomized 1 : 1 to receive maraviroc 150 mg once daily or tenofovir/emtricitabine once daily each with darunavir/ritonavir once daily for 96 weeks. The primary endpoint was the proportion of participants with HIV-1 RNA less than 50 copies/ml (Food and Drug Administration snapshot algorithm) at Week 48. A substudy evaluated bone mineral density, body fat distribution and serum bone turnover markers. RESULTS: Seven hundred and ninety-seven participants were dosed (maraviroc, n = 396; tenofovir/emtricitabine, n = 401). The Data Monitoring Committee recommended early study termination due to inferior efficacy in the maraviroc group. At Week 48, the proportion of participants with HIV-1 RNA less than 50 copies/ml was 77.3% for maraviroc and 86.8% for tenofovir/emtricitabine [difference of -9.54% (95% confidence interval: -14.83 to -4.24)]. More maraviroc participants discontinued for lack of efficacy, which was not associated with non-R5 tropism or resistance. Discontinuations for adverse events, Category C events, Grade 3/4 adverse events and laboratory abnormalities were similar between groups. CONCLUSION: A once-daily nucleos(t)ide-sparing two-drug regimen of maraviroc and darunavir/ritonavir was inferior to a three-drug regimen of tenofovir/emtricitabine and darunavir/ritonavir in antiretroviral-naive adults. PMID- 26854811 TI - Immunologic profiles distinguish aviremic HIV-infected adults. AB - OBJECTIVE: Prior hypothesis-driven studies identified immunophenotypic characteristics associated with the control of HIV replication without antiretroviral therapy (HIV controllers) as well as with the degree of CD4 T-cell recovery during ART. We hypothesized that an unbiased 'discovery-based' approach might identify novel immunologic characteristics of these phenotypes. DESIGN: We performed immunophenotyping on four 'aviremic' patient groups: HIV controllers (n = 98), antiretroviral-treated immunologic nonresponders (CD4 < 350; n = 59), antiretroviral-treated immunologic responders (CD4 > 350, n = 142), and as a control group HIV-negative adults (n = 43). We measured levels of T-cell maturation, activation, dysfunction, senescence, functionality, and proliferation. METHODS: Supervised learning assessed the relative importance of immune parameters in predicting clinical phenotypes (controller, immunologic responder, or immunologic nonresponder). Unsupervised learning clustered immune parameters and examined if these clusters corresponded to clinical phenotypes. RESULTS: HIV controllers were characterized by high percentages of HIV-specific T cell responses and decreased percentages of cells expressing human leukocytic antigen-antigen D related in naive, central memory, and effector T-cell subsets. Immunologic nonresponders were characterized by higher percentages of CD4 T cells that were TNFalpha+ or INFgamma+, higher percentages of activated naive and central memory T cells, and higher percentages of cells expressing programmed cell death protein 1. Unsupervised learning found two distinct clusters of controllers and two distinct clusters of immunologic nonresponders, perhaps suggesting different mechanisms for the clinical outcomes. CONCLUSION: Our discovery-based approach confirmed previously reported characteristics that distinguish aviremic individuals, but also identified novel immunologic phenotypes and distinct clinical subpopulations that should lead to more focused pathogenesis studies that might identify targets for novel therapeutic interventions. PMID- 26854813 TI - No changes in sexual behaviour after voluntary medical male circumcision in the Dominican Republic. PMID- 26854812 TI - Is nelfinavir exposure associated with cancer incidence in HIV-positive individuals? AB - OBJECTIVE: Nelfinavir exhibits potent anticancer properties against a range of tumours. However, in 2006/2007, nelfinavir supplies were accidently contaminated with a carcinogen. This analysis investigated the association between nelfinavir use and cancer risk in HIV-positive persons. DESIGN: Observational cohort study. METHODS: D:A:D study data was analysed using Poisson regression models to examine associations between cancer incidence and cumulative nelfinavir exposure, current nelfinavir exposure, and exposure to nelfinavir between 1 July 2006-30 June 2007. RESULTS: A total of 42 006 individuals (50% white, 73% male) contributed 303 005 person-years of follow-up between 1 January 2004 and 1 February 2014. At study enrolment, median age was 40 [interquartile range (IQR) 33-46] years and 8305 individuals had a history of nelfinavir use [median duration 1.7 (IQR 0.7-3.4) years]. During follow-up, nelfinavir was used by 2476 individuals for a median of 1.7 (IQR 0.7-3.8) years; 1063 were exposed to nelfinavir between 1 July 2006 and 30 June 2007. Overall, 2279 cancers were diagnosed at a rate of 0.75 [95% confidence interval (95% CI) 0.72-0.78] per 100 person-years. Neither greater cumulative exposure to nelfinavir [adjusted risk ratio (aRR) 0.93 for every additional 5 years, 95% CI 0.82-1.06, P = 0.26] nor current use of nelfinavir (aRR 0.98 vs other protease inhibitor use, 95% CI 0.68-1.41, P = 0.92) were associated with cancer risk. The adjusted risk of cancer for participants exposed to nelfinavir between 1 July 2006 and 30 June 2007 compared to those receiving other treatment over this period was 1.07 (95% CI 0.78-1.46, P = 0.68). CONCLUSION: Nelfinavir use was not associated with a lower cancer incidence than other protease inhibitor regimens. As of February 2014, exposure to the 2006/2007 contamination of nelfinavir does not appear to be associated with increased cancer incidence. PMID- 26854814 TI - Simplified HIV testing and treatment reduces mortality rate by over 60% in a trial in China. PMID- 26854815 TI - Treatment-refractory posttraumatic stress disorder (TRPTSD): a review and framework for the future. AB - Post-traumatic stress disorder (PTSD) is a serious psychiatric consequence of trauma that occurs in a proportion of individuals exposed to life-threatening events. Trauma-focused psychotherapy is often recommended as first choice for those who do not recover spontaneously. But many individuals require medications. In the US, only paroxetine (PRX) and sertraline (SRT) are FDA approved for PTSD. But response and remission rates with these medications are low, so numerous other pharmacologic interventions have been tried. To date, there has not been a systematic review of the data on what are the best next-step pharmacologic strategies for individuals who fail standard treatments. To that end, we review 168 published trials of medications other than PRX or SRT and provide a detailed analysis of the 88/168 studies that describe alternative pharmacologic interventions in patients refractory to other treatment. We also review clinical factors relevant to treatment-refractory PTSD; the neurobiology of extinction, as well as evidence-based psychotherapy and neuromodulation strategies for this condition. PMID- 26854816 TI - Early Supported Discharge/Hospital At Home For Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Review and Meta-Analysis. AB - A systematic review and meta-analysis was performed to assess the safety, efficacy and cost of Early Supported Discharge (ESD) and Hospital at Home (HAH) compared to Usual Care (UC) for patients with acute exacerbation of COPD (AECOPD). The structure of ESD/HAH schemes was reviewed, and analyses performed assuming return to hospital during the acute period (prior to discharge from home treatment) was, and was not, considered a readmission. The pre-defined search strategy completed in November 2014 included electronic databases (Medline, Embase, Amed, BNI, Cinahl and HMIC), libraries, current trials registers, national organisations, key respiratory journals, key author contact and grey literature. Randomised controlled trials (RCTs) comparing ESD/HAH to UC in patients admitted with AECOPD, or attending the emergency department and triaged for admission, were included. Outcome measures were mortality, all-cause readmissions to 6 months and cost. Eight RCTs were identified; seven reported mortality and readmissions. The structure of ESD/HAH schemes, particularly selection criteria applied and level of support provided, varied considerably. Compared to UC, ESD/HAH showed a trend towards lower mortality (RRMH = 0.66; 95% CI 0.40-1.09, p = 0.10). If return to hospital during the acute period was not considered a readmission, ESD/HAH was associated with fewer readmissions (RRMH = 0.74, 95% CI: 0.60-0.90, p = 0.003), but if considered a readmission, the benefit was lost (RRMH = 0.84; 95% CI 0.69-1.01, p = 0.07). Costs were lower for ESD/HAH than UC. ESD/HAH is safe in selected patients with an AECOPD. Further research is required to define optimal criteria to guide patient selection and models of care. PMID- 26854817 TI - Simultaneous reconstruction of the activity image and registration of the CT image in TOF-PET. AB - Previously, maximum-likelihood methods have been proposed to jointly estimate the activity image and the attenuation image or the attenuation sinogram from time-of flight (TOF) positron emission tomography (PET) data. In this contribution, we propose a method that addresses the possible alignment problem of the TOF-PET emission data and the computed tomography (CT) attenuation data, by combining reconstruction and registration. The method, called MLRR, iteratively reconstructs the activity image while registering the available CT-based attenuation image, so that the pair of activity and attenuation images maximise the likelihood of the TOF emission sinogram. The algorithm is slow to converge, but some acceleration could be achieved by using Nesterov's momentum method and by applying a multi-resolution scheme for the non-rigid displacement estimation. The latter also helps to avoid local optima, although convergence to the global optimum cannot be guaranteed. The results are evaluated on 2D and 3D simulations as well as a respiratory gated clinical scan. Our experiments indicate that the proposed method is able to correct for possible misalignment of the CT-based attenuation image, and is therefore a very promising approach to suppressing attenuation artefacts in clinical PET/CT. When applied to respiratory gated data of a patient scan, it produced deformations that are compatible with breathing motion and which reduced the well known attenuation artefact near the dome of the liver. Since the method makes use of the energy-converted CT attenuation image, the scale problem of joint reconstruction is automatically solved. PMID- 26854818 TI - Synthesis, Ensemble, and Single Molecule Characterization of a Diphenyl-Acetylene Linked Terrylenediimide Dimer. AB - The synthesis and the photophysical characterization at the ensemble and single molecule level of a terrylenediimide (TDI) dimer are reported. The spectroscopic experimental data are compared with those obtained for the corresponding model compound TDI. Steady-state and ps time-correlated single photon counting have shown that both chromophores in the TDI dimer are in the weak coupling regime allowing their interaction by Forster resonance energy transfer. Femtosecond transient absorption experiments showed an excitation power dependence of the fluorescence decay, which could indicate the occurrence of singlet-singlet annihilation. Single molecule intensity traces were investigated for the TDI dimer and suggested two intensity levels. For both intensity levels several parameters among which emission maximum, fluorescence decay times, antibunching, blinking off-times and rate of dark state formation were compared. The blinking analysis revealed that the yield of dark state formation is an order of magnitude higher when the two chromophores are still active compared to the case where one is photobleached. The off-times remain however similar. PMID- 26854819 TI - Effect of Mirtazapine Treatment on Serum Levels of Brain-Derived Neurotrophic Factor and Tumor Necrosis Factor-alpha in Patients of Major Depressive Disorder with Severe Depression. AB - BACKGROUND: This study evaluated the clinical efficacy of mirtazapine and its effect on serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-alpha) levels in patients of major-depressive disorder (MDD) with severe depression. METHODS: Patients (aged 18-60) with MDD diagnosed by DSM IV criteria, and Hamilton Rating Scale for Depression (HAM-D) score >=25 were included (n = 30). Mirtazapine was given in the doses of 30 mg/day. All patients were followed up for 12 weeks for the evaluation of clinical efficacy, safety along with serum BDNF and TNF-alpha levels. RESULTS: HAM-D score at the start of treatment was 30.1 +/- 1.92, which significantly (p < 0.05) reduced to 13.47 +/- 1.77 at 12 weeks of treatment. In responders, mean serum BDNF levels at the start of treatment were 2.32 +/- 0.3 ng/ml, which significantly (p < 0.05) increased to 2.79 +/- 0.33 ng/ml at 12 weeks of treatment and mean serum TNF-alpha levels at the start were 5.18 +/- 0.67 pg/ml, which significantly decreased to 4.36 +/- 0.72 pg/ml (p < 0.05) at 12 weeks of treatment. CONCLUSION: Our results suggest that mirtazapine is effective and well tolerated in severely depressed patients and treatment response is associated with an increase in serum BDNF and a decrease in serum TNF-alpha levels. PMID- 26854820 TI - Incidence of nonresponse and individual patterns of response following sprint interval training. AB - The current study sought to explore the incidence of nonresponders for maximal or submaximal performance following a variety of sprint interval training (SIT) protocols. Data from 63 young adults from 5 previously published studies were utilized in the current analysis. Nonresponders were identified using 2 times the typical error (TE) of measurement for peak oxygen uptake (2 * TE = 1.74 mL/(kg.min)), lactate threshold (2 * TE = 15.7 W), or 500 kcal time-to-completion (TTC; 2 * TE = 306 s) trial. TE was determined on separate groups of participants by calculating the test-retest variance for each outcome. The overall rate of nonresponders for peak oxygen uptake across all participants studied was 22% (14/63) with 4 adverse responders observed. No nonresponders for peak oxygen uptake were observed in studies where participants trained 4 times per week (n = 18), while higher rates were observed in most studies requiring training 3 times per week (30%-50%; n = 45). A nonresponse rate of 44% (8/18) and 50% (11/22) was observed for the TTC test and lactate threshold, respectively. No significant correlations were observed between the changes in peak oxygen uptake and TTC (r = 0.014; p = 0.96) or lactate threshold (r = 0.17; p = 0.44). The current analysis demonstrates a significant incidence of nonresponders for peak oxygen uptake and heterogeneity in the individual patterns of response following SIT. Additionally, these data support the importance of training dose and suggest that the incidence of nonresponse may be mitigated by utilizing the optimal dose of SIT. PMID- 26854821 TI - Effects of Standardized Eriobotrya japonica Extract in LP-BM5 Murine Leukemia Viruses-Induced Murine Immunodeficiency Syndrome. AB - Folk medicine has long employed leaves from Eriobotrya japonica Lindl. (Rosaceae) (LEJ) as relieving many diseases including chronic bronchitis and high fever. In this study, we investigated the immunomodulatory effects of leaves from LEJ water extracts (LEJE) in LP-BM5 murine leukemia viruses (MuLV)-induced immune-deficient animal model. Dietary supplementation of LEJE (100, 300, 500 mg/kg) began on the day of LP-BM5 MuLV infection and continued for 12 weeks. Dietary supplementation of LEJE inhibited LP-BM5 MuLV-induced splenomegaly and lymphadenopathy. Moreover, LEJE attenuated reductions of T- and B-cell proliferation and Th1/Th2 cytokine imbalance in LP-BM5. We found that dietary supplements of LEJE suppressed the hypergammaglobulinemia by ameliorating LP-BM5 MuLV infection-induced B-cell dysfunction and production of pro-inflammatory cytokines. We suggest that Eriobotrya japonica may have beneficial immunomodulatory effects, improving the balance of Th1/Th2 cytokines and anti-inflammatory effects. PMID- 26854822 TI - Metabolic characterization of imatinib-resistant BCR-ABL T315I chronic myeloid leukemia cells indicates down-regulation of glycolytic pathway and low ROS production. AB - Long-term imatinib treatment induces drug-resistant chronic myeloid leukemia (CML) cells harboring T315I gate keeper mutation of breakpoint cluster region (BCR)-ABL oncogenic kinase. However, although cell proliferation is coupled with cellular energy status in CML carcinogenesis, the metabolic characteristics of T315I-mutant CML cells have never been investigated. Here, we analyzed cell proliferation activities and metabolic phenotypes, including cell proliferation, oxygen consumption, lactate production, and redox state in the KBM5 (imatinib sensitive) and KBM5-T315I (imatinib-resistant) CML cell lines. Interestingly, KBM5-T315I cells showed decreased cell proliferation, lactate production, fatty acid synthesis, ROS production, and down regulation of mRNA expression related to ROS scavengers, such as SOD2, catalase, GCLm, and GPx1. Taken together, our data demonstrate that the lower growth ability of KBM5-T315I CML cells might be related to the decreased expression of glycolysis-related genes and ROS levels, and this will be used to identify therapeutic targets for imatinib resistance in CML. PMID- 26854805 TI - Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept. AB - Schizophrenia is a devastating psychiatric illness with high heritability. Brain structure and function differ, on average, between people with schizophrenia and healthy individuals. As common genetic associations are emerging for both schizophrenia and brain imaging phenotypes, we can now use genome-wide data to investigate genetic overlap. Here we integrated results from common variant studies of schizophrenia (33,636 cases, 43,008 controls) and volumes of several (mainly subcortical) brain structures (11,840 subjects). We did not find evidence of genetic overlap between schizophrenia risk and subcortical volume measures either at the level of common variant genetic architecture or for single genetic markers. These results provide a proof of concept (albeit based on a limited set of structural brain measures) and define a roadmap for future studies investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. PMID- 26854823 TI - Increased retinal mtDNA damage in the CFH variant associated with age-related macular degeneration. AB - Age-related macular degeneration (AMD) is a major cause of blindness among the elderly in the developed world. Genetic analysis of AMD has identified 34 high risk loci associated with AMD. The genes at these high risk loci belong to diverse biological pathways, suggesting different mechanisms leading to AMD pathogenesis. Thus, therapies targeting a single pathway for all AMD patients will likely not be universally effective. Recent evidence suggests defects in mitochondria (mt) of the retinal pigment epithelium (RPE) may constitute a key pathogenic event in some AMD patients. The purpose of this study is to determine if individuals with a specific genetic background have a greater propensity for mtDNA damage. We used human eyebank tissues from 76 donors with AMD and 42 age matched controls to determine the extent of mtDNA damage in the RPE that was harvested from the macula using a long extension polymerase chain reaction assay. Genotype analyses were performed for ten common AMD-associated nuclear risk alleles (ARMS2, TNFRSF10A, CFH, C2, C3, APOE, CETP, LIPC, VEGF and COL10A1) and mtDNA haplogroups. Sufficient samples were available for genotype association with mtDNA damage for TNFRSF10A, CFH, CETP, VEGFA, and COL10A1. Our results show that AMD donors carrying the high risk allele for CFH (C) had significantly more mtDNA damage compared with donors having the wild-type genetic profile. The data from an additional 39 donors (12 controls and 27 AMD) genotyped for CFH alleles further supported these findings. Taken together, these studies provide the rationale for a more personalized approach for treating AMD by uncovering a significant correlation between the CFH high risk allele and accelerated mtDNA damage. Patients harboring this genetic risk factor may benefit from therapies that stabilize and protect the mt in the RPE. PMID- 26854825 TI - Multidisciplinary molecular diagnostics: the 9th European meeting on molecular diagnostics. AB - This report presents a summary of the 9th European Meeting on Molecular Diagnostics held in Noordwijk, The Netherlands, 14-16 October 2015. This 3-day conference covered many relevant topics in the field of molecular diagnostics in humans, including infectious disease, oncology, outbreak management, population based cancer screening, standardization and quality control, chronic diseases and pharmacogenetics. Beyond these different areas, shared values are new technologies and novel technical and clinical applications. Approximately 450 participants, the majority coming from European countries, attended the meeting. Besides high quality scientific presentations, more than 35 diagnostic companies presented their latest innovations, altogether in an informal and inspiring scientific ambience. PMID- 26854826 TI - A simple and rapid HPLC-DAD method for simultaneously monitoring the accumulation of alkaloids and precursors in different parts and different developmental stages of Catharanthus roseus plants. AB - A rapid and simple reversed phase liquid chromatographic system has been developed for simultaneous analysis of terpenoid indole alkaloids (TIAs) and their precursors. This method allowed separation of 11 compounds consisting of eight TIAs (ajmalicine, serpentine, catharanthine, vindoline, vindolinine, vincristine, vinblastine, and anhydrovinblastine) and three related precursors i.e., tryptophan, tryptamine and loganin. The system has been applied for screening the TIAs and precursors in Catharanthus roseus plant extracts. In this study, different organs i.e., flowers, leaves, stems, and roots of C. roseus were investigated. The results indicate that TIAs and precursor accumulation varies qualitatively and quantitatively in different organs of C. roseus. The precursors showed much lower levels than TIAs in all organs. Leaves and flowers accumulate higher level of vindoline, catharanthine and anhydrovinblastine while roots have higher level of ajmalicine, vindolinine and serpentine. Moreover, the alkaloid profiles of leaves harvested at different ages and different growth stages were studied. The results show that the levels of monoindole alkaloids decreased while bisindole alkaloids increased with leaf aging and upon plant growth. The HPLC method has been successfully applied to detect TIAs and precursors in different types of C. roseus samples to facilitate further study of the TIA pathway and its regulation in C. roseus plants. PMID- 26854827 TI - Survival in Frontotemporal Dementia Phenotypes: A Meta-Analysis. AB - BACKGROUND: Survival in frontotemporal dementia (FTD) is not well understood. We conducted a mixed effects meta-analysis of survival in FTD to examine phenotype differences and contributory factors. METHODS: The PubMed, Medline, EMBASE, CINAHL, PsycINFO and Cochrane databases were searched for studies describing survival or natural history of behavioral variant FTD (bvFTD), progressive non fluent aphasia (PNFA), semantic dementia (SD), FTD with amyotrophic lateral sclerosis (FTD-ALS), progressive supranuclear palsy and corticobasal degeneration. There were no language restrictions. RESULTS: We included 27 studies (2,462 subjects). Aggregate mean and median survival were derived for each phenotype and, for comparison, Alzheimer's disease (AD) (using data from the selected studies). Survival was shortest in FTD-ALS (2.5 years). Mean survival was longest in bvFTD and PNFA (8 years) and median survival in SD (12 years). AD was comparable in survival to all except FTD-ALS. Age and sex did not affect survival; the education effect was equivocal. Heterogeneity in FTD survival was largely, but not wholly, explained by phenotypes. CONCLUSIONS: Survival differs for FTD phenotypes but, except for FTD-ALS, compares well to AD survival. Elucidating the potential causes of within-phenotype heterogeneity in survival (such as complicating features and comorbidities) may open up opportunities for tailored interventions. PMID- 26854824 TI - Differential cytotoxic effects of 7-dehydrocholesterol-derived oxysterols on cultured retina-derived cells: Dependence on sterol structure, cell type, and density. AB - Tissue accumulation of 7-dehydrocholesterol (7DHC) is a hallmark of Smith-Lemli Opitz Syndrome (SLOS), a human inborn error of the cholesterol (CHOL) synthesis pathway. Retinal 7DHC-derived oxysterol formation occurs in the AY9944-induced rat model of SLOS, which exhibits a retinal degeneration characterized by selective loss of photoreceptors and associated functional deficits, Muller cell hypertrophy, and engorgement of the retinal pigment epithelium (RPE) with phagocytic inclusions. We evaluated the relative effects of four 7DHC-derived oxysterols on three retina-derived cell types in culture, with respect to changes in cellular morphology and viability. 661W (photoreceptor-derived) cells, rMC-1 (Muller glia-derived) cells, and normal diploid monkey RPE (mRPE) cells were incubated for 24 h with dose ranges of either 7-ketocholesterol (7kCHOL), 5,9 endoperoxy-cholest-7-en-3beta,6alpha-diol (EPCD), 3beta,5alpha-dihydroxycholest-7 en-6-one (DHCEO), or 4beta-hydroxy-7-dehydrocholesterol (4HDHC); CHOL served as a negative control (same dose range), along with appropriate vehicle controls, while staurosporine (Stsp) was used as a positive cytotoxic control. For 661W cells, the rank order of oxysterol potency was: EPCD > 7kCHOL >> DHCEO > 4HDHC ~ CHOL. EC50 values were higher for confluent vs. subconfluent cultures. 661W cells exhibited much higher sensitivity to EPCD and 7kCHOL than either rMC-1 or mRPE cells, with the latter being the most robust when challenged, either at confluence or in sub-confluent cultures. When tested on rMC-1 and mRPE cells, EPCD was again an order of magnitude more potent than 7kCHOL in compromising cellular viability. Hence, 7DHC-derived oxysterols elicit differential cytotoxicity that is dose-, cell type-, and cell density-dependent. These results are consistent with the observed progressive, photoreceptor-specific retinal degeneration in the rat SLOS model, and support the hypothesis that 7DHC-derived oxysterols are causally linked to that retinal degeneration as well as to SLOS. PMID- 26854828 TI - Abhydrolase domain containing 2, an androgen target gene, promotes prostate cancer cell proliferation and migration. AB - BACKGROUND: The androgen receptor (AR) plays a key role in the development of prostate cancer. AR signalling mediates the expression of androgen-responsive genes, which are involved in prostate cancer development and progression. Our previous chromatin immunoprecipitation study showed that the region of abhydrolase domain containing 2 (ABHD2) includes a functional androgen receptor binding site. In this study, we demonstrated that ABHD2 is a novel androgen responsive gene that is overexpressed in human prostate cancer tissues. METHODS: The expression levels of ABHD2 in androgen-sensitive cells were evaluated by quantitative reverse transcription polymerase chain reaction and western-blot analyses. LNCaP and VCaP cells with ABHD2 overexpression or short interfering RNA (siRNA) knockdown were used for functional analyses. ABHD2 expression was examined in clinical samples of prostate cancer by immunohistochemistry. RESULTS: We showed that ABHD2 expression is increased by androgen in LNCaP and VCaP cells. This androgen-induced ABHD2 expression was diminished by bicalutamide. While stable expression of ABHD2 affected the enhancement of LNCaP cell proliferation and migration, siRNA-mediated ABHD2 knockdown suppressed cell proliferation and migration. In addition, the siRNA treatment significantly repressed the tumour growth derived from LNCaP cells in athymic mice. Immunohistochemical analysis of ABHD2 expression in tumour specimens showed a positive correlation of ABHD2 immunoreactivity with high Gleason score and pathological N stage. Moreover, patients with high immunoreactivity of ABHD2 showed low cancer-specific survival rates and a resistance to docetaxel-based chemotherapy. CONCLUSION: ABHD2 is a novel androgen-regulated gene that can promote prostate cancer growth and resistance to chemotherapy, and is a novel target for diagnosis and treatment of prostate cancer. PMID- 26854829 TI - Validity of SenseWear(r) Armband v5.2 and v2.2 for estimating energy expenditure. AB - We compared SenseWear Armband versions (v) 2.2 and 5.2 for estimating energy expenditure in healthy adults. Thirty-four adults (26 women), 30.1 +/- 8.7 years old, performed two trials that included light-, moderate- and vigorous-intensity activities: (1) structured routine: seven activities performed for 8-min each, with 4-min of rest between activities; (2) semi-structured routine: 12 activities performed for 5-min each, with no rest between activities. Energy expenditure was measured by indirect calorimetry and predicted using SenseWear v2.2 and v5.2. Compared to indirect calorimetry (297.8 +/- 54.2 kcal), the total energy expenditure was overestimated (P < 0.05) by both SenseWear v2.2 (355.6 +/- 64.3 kcal) and v5.2 (342.6 +/- 63.8 kcal) during the structured routine. During the semi-structured routine, the total energy expenditure for SenseWear v5.2 (275.2 +/- 63.0 kcal) was not different than indirect calorimetry (262.8 +/- 52.9 kcal), and both were lower (P < 0.05) than v2.2 (312.2 +/- 74.5 kcal). The average mean absolute per cent error was lower for the SenseWear v5.2 than for v2.2 (P < 0.001). SenseWear v5.2 improved energy expenditure estimation for some activities (sweeping, loading/unloading boxes, walking), but produced larger errors for others (cycling, rowing). Although both algorithms overestimated energy expenditure as well as time spent in moderate-intensity physical activity (P < 0.05), v5.2 offered better estimates than v2.2. PMID- 26854830 TI - Ultrafast and Efficient Transport of Hot Plasmonic Electrons by Graphene for Pt Free, Highly Efficient Visible-Light Responsive Photocatalyst. AB - We report that reduced graphene-coated gold nanoparticles (r-GO-AuNPs) are excellent visible-light-responsive photocatalysts for the photoconversion of CO2 into formic acid (HCOOH). The wavelength-dependent quantum and chemical yields of HCOOH shows a significant contribution of plasmon-induced hot electrons for CO2 photoconversion. Furthermore, the presence and reduced state of the graphene layers are critical parameters for the efficient CO2 photoconversion because of the electron mobility of graphene. With an excellent selectivity toward HCOOH (>90%), the quantum yield of HCOOH using r-GO-AuNPs is 1.52%, superior to that of Pt-coated AuNPs (quantum yield: 1.14%). This indicates that r-GO is a viable alternative to platinum metal. The excellent colloidal stability and photocatalytic stability of r-GO-AuNPs enables CO2 photoconversion under more desirable reaction conditions. These results highlight the role of reduced graphene layers as highly efficient electron acceptors and transporters to facilitate the use of hot electrons for plasmonic photocatalysts. The femtosecond transient spectroscopic analysis also shows 8.7 times higher transport efficiency of hot plasmonic electrons in r-GO-AuNPs compared with AuNPs. PMID- 26854831 TI - "Grow the Beard, Wear the Costume": Resisting Weight and Sexual Orientation Stigmas in the Bear Subculture. AB - Being gay and being overweight are two stigmatized statuses in the United States. A range of work has considered the experience of being stigmatized and the consequences of stereotypes for overweight individuals and sexual minorities, but less research has examined the intersection of these two stigmas among larger gay men or collective efforts to resist such stigma. This study qualitatively examines a subculture of gay men, the bears, to test theoretical models of stigma resistance. The analysis demonstrates the transferability of stigma resistance among multiple stigmatized attributes and the use of multiple strategies to resist one stigma. At the same time, it shows how subcultural dynamics both aid and undermine the resistance toward stigma, and the risk of reinforcing stigma's effect through criticizing others who embody a stereotype. The results also demonstrate how resistance strategies are both empowering and psychologically taxing for stigmatized individuals. PMID- 26854832 TI - [Prevalence and risk factors of drug induced liver disease: a survey based study in pharmacies]. AB - AIM: The reported incidence of drug-induced liver injury (DILI) ranges from 1 in 10,000 to 1 in 100,000 patients for most drugs, but the true incidence is expected to be much higher. Several risk factors for DILI susceptibility have been suggested, however there is insufficient data to define an individual risk profile. Therefore it was our aim to study the prevalence of DILI and potential risk factors within adult pharmacy customers in Germany. METHODS: We conducted two 6 week-survey studies in 30 pharmacies in 2011 and 2012, respectively, using a newly developed questionnaire comprising questions on demography, (liver) diseases, liver enzyme activities, and drug history. In each study, anonymized questionnaires were presented to non-selected adult customers taking (non )prescription drugs. RESULTS: Combining the datasets from the 2011 and 2012 surveys, in total 1098 questionnaires were evaluated (mean age 57.7 +/- 17.1 years; 62.6 % females, return rate 15.25 %). Overall, 141 individuals (12.8 %) reported elevated liver enzymes due to drugs, in 65 cases (5.9 %) the medication had to be stopped, and 20 customers (1.8 %) reported that they had been admitted to hospital due to DILI. Compared to individuals without adverse hepatic drug reactions (n = 957), the 141 persons with potential DILI presented more often the following risk factors in multivariate analysis: chronic liver disease (14.4 % vs. 2.4 %, odds ratio [OR] 4.2, 95 % confidence interval [CI] 2.0 - 9.0), chronic renal insufficiency (20.0 vs. 6.8 %, OR 2.2, 95 % CI 1.3 - 3.7), diabetes (34 vs. 15.3 %, OR 2.0, 95 % CI 1.3 - 3.2), family history of chronic liver disease (19.9 vs. 7.7 %, OR 2.1, 95 % CI 1.2 - 3.6), and continuous drug intake for more than 5 years (80.9 vs. 59.3 %, OR 2.1, 95 % CI 1.3 - 3.5). CONCLUSION: These studies show an unexpected high prevalence of DILI in pharmacy customers and identify multiple potential risk factors. PMID- 26854833 TI - [Employees with chronic diseases - additional results of randomized controlled trial among adult members of a German statutory health insurance with inflammatory bowel diseases]. AB - BACKGROUND: Chronic and prognostically doubtful diseases like inflammatory bowel diseases (IBD) often lead to reduced work ability. Whether self-management interventions have positive effects on work related outcomes is so far unclear. METHODS: Data from a randomized controlled trial of adult members of a German statutory health insurance with medically confirmed IBD were reanalyzed. We focused on 337 gainfully employed study participants. They completed a screening questionnaire enquiring about 22 disease-related bio-psycho-social problems. The intervention group (IG) received individualized (problem-adapted) written recommendations; the control group remained under usual care. 12 months later a follow-up questionnaire was employed, data on sick leave were made available by the health insurance. RESULTS: The IG showed beneficial effects in all primary outcomes (EuroQol visual analog scale score, index for measuring participation restriction and number of self-reported disability days). At baseline one in four of the employed participants reported a negative subjective prognosis of their work capacity (assessed by means of a 3-item Likert scale, SPE scale). No positive intervention effects on work-related outcomes (subjective prognosis of gainful employment, episodes and days of sick leave) could be detected. CONCLUSIONS: In IBD patients work and earning capacity is often at risk and should be regularly assessed. Effective interventions to protect or restore gainful employment are needed. Medical-vocational rehabilitation could be a treatment option; its efficacy and benefit (in IBD) are still to be demonstrated. PMID- 26854834 TI - Feasibility of a colon capsule overnight procedure followed by colonoscopy. AB - BACKGROUND AND AIM: Due to limited acceptance of colonoscopy as diagnostic and screening test alternatives are warranted. Colon capsule endoscopy (CCE) has been shown to be a possible filter test, but because of logistical issues a second bowel preparation is usually required, if consecutive colonoscopy is needed. We therefore evaluated the feasibility of a single bowel preparation for both overnight CCE and (therapeutical) colonoscopy thereafter. METHODS: Patients from two university hospitals referred to undergo colonoscopy were prospectively included in a dual centre feasibility study. A polyethylene glycol (PEG) based bowel preparation-schedule with ingestion of a colon capsule endoscopy (CCE) at 10pm and subsequent colonoscopy at about 12am on the next day was investigated. The first generation PillCam colon capsule was used with 4 different preparation protocols containing several prokinetics in different compositions (i. e. metoclopramide, erythromycin, sennosoides). The main endpoint was the proportion of patients who completed both CCE and colonoscopy; secondary endpoints were capsule transit times, amount of colon seen on CCE, bowel cleanliness, sensitivity and specifity of CCE and patients' acceptance. RESULTS: 50 patients between 18 and 75 years were included. The sequence of overnight colon capsule endoscopy and colonoscopy was successfully completed in all but one (one refused colonoscopy). The capsule was excreted during recording time in 86 % of examinations, visualization of the complete colon was possible in 60 %, but adequate colon preparation was achieved in only 45 % irrespective of the regimen used. The preparation regimen consisting of a PEG-solution, erythromycin as prokinetic drug followed by PEG-solution as boost showed the largest proportion of adequate preparations. Overall sensitivity and specificity of CCE for polyps of any size were 65 % and 76 %, respectively. 26 of 30 patients (86.7 %) returned the subjective assessment questionnaire. 23 patients (88 %) reported mild to no discomfort or embarrassment during CCE, whereas 15 patients (58 %) did during the preparation procedure. Drinking the purgative solution was the most inconvenient step in 84 % of cases, drinking the boosts during CCE the second inconvenient step (60 %). CONCLUSION: Overnight CCE-procedure followed by direct capsule reading is feasible and safe and might avoid repetitive bowel preparation for subsequent colonoscopy. The bowel preparation needs to be improved. PMID- 26854835 TI - [Chylous ascites and acute appendicitis - more than an accidental finding?]. AB - INTRODUCTION: Chylous ascites with a simultaneously presenting acute appendicitis is a uncommon finding which has been rarely reported in present literature. CASE REPORT: We present the case of a 36 years old patient showing the clinical signs of an acute appendicitis with an intraoperative finding of chylous ascites. DISCUSSION: The causing factors for chylous ascites are numerous, the clinical manifestations nonspecific. Thus the adequate diagnostic measures vary. The therapy is mainly based on medicational and dietary treatment but also benefits from a surgical approach. PMID- 26854836 TI - Percutaneous sclerotherapy of liver and renal cysts, comments on the EFSUMB guidelines. AB - Cystic lesions in the liver and kidneys are common incidental findings. They are generally benign and require no treatment. They can appear sporadically or as part of a syndrome, and are characterised by their anechoic structure and posterior enhancement in ultrasound imaging. Increased size, haemorrhage or infection of a cyst can lead to development of symptoms. Along with surgical options and laparoscopic cyst fenestration, ultrasound-guided sclerotherapy of symptomatic cysts represents an effective and safe minimally invasive treatment option. PMID- 26854837 TI - [ASCO-update 2015 - highlights of the 51. meeting of the american society of clinical oncology/ASCO 2015]. AB - The field of gastrointestinal oncology is rapidly developing, on the one hand through the identification of novel molecular targets and therapeutic principles, on the other hand through the establishment and improvement of multidisciplinary treatment strategies. The following manuscript summarizes the most important trial results of the ASCO Meeting 2015 for gastrointestinal cancers. Besides trials on perioperative treatment of esophageal-, pancreatic- and colon cancer, we will present impressive data on new therapeutic strategies such as immunotherapy in gastric-, liver and microsatellite instable colorectal cancer. The trials will be put into context by the authors. PMID- 26854838 TI - Detection of carbapenemase-producing gram-negative bacteria using a simplified Carba NP test. AB - A simplified Carba NP test (CNPt), the CNPt-direct, was evaluated for carbapenemase detection using 272 gram-negative bacteria. Compared to the Modified Hodge test, the CNPt-direct had higher sensitivity (98.2% vs. 71.6%). The simplified Carba NP is an accurate, cheap and simple test for rapid carbapenemase detection. PMID- 26854839 TI - Producing superhydrophobic roof tiles. AB - Superhydrophobic materials can find promising applications in the field of building. However, their application has been very limited because the synthesis routes involve tedious processes, preventing large-scale application. A second drawback is related to their short-term life under outdoor conditions. A simple and low-cost synthesis route for producing superhydrophobic surfaces on building materials is developed and their effectiveness and their durability on clay roof tiles are evaluated. Specifically, an organic-inorganic hybrid gel containing silica nanoparticles is produced. The nanoparticles create a densely packed coating on the roof tile surface in which air is trapped. This roughness produces a Cassie-Baxter regime, promoting superhydrophobicity. A surfactant, n octylamine, was also added to the starting sol to catalyze the sol-gel process and to coarsen the pore structure of the gel network, preventing cracking. The application of ultrasound obviates the need to use volatile organic compounds in the synthesis, thereby making a 'green' product. It was also demonstrated that a co-condensation process effective between the organic and inorganic species is crucial to obtain durable and effective coatings. After an aging test, high hydrophobicity was maintained and water absorption was completely prevented for the roof tile samples under study. However, a transition from a Cassie-Baxter to a Wenzel state regime was observed as a consequence of the increase in the distance between the roughness pitches produced by the aging of the coating. PMID- 26854840 TI - Oxidative Stress and Advanced Glycation End Products in Hashimoto's Thyroiditis. AB - BACKGROUND: Oxidative stress, which occurs as a result of an imbalance between free-radical production and antioxidant defense mechanisms, has been implicated in the pathogenesis of several autoimmune disorders, including thyroid diseases. Importantly, it has been correlated to thyroid dysfunction. This study investigated the changes in oxidative balance in euthyroid Hashimoto's thyroiditis (HT) by means of specific serum tests, such as derived reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) test. In addition, advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs)--compounds formed by the transformation of proteins- were evaluated as potential new markers of oxidative stress in this disease. METHODS: This study included 134 euthyroid subject: 71 newly diagnosed HT patients (63 females; M age = 38 +/- 13 years) and 63 age and sex-matched healthy controls. None of them were on thyroxine therapy. RESULTS: Serum d-ROMs were elevated, and BAP decreased in HT patients compared with controls (p < 0.001), and the two parameters were inversely correlated (r = -0.211; p = 0.027), clearly indicating an enhanced oxidative stress. Furthermore, AGE levels were higher in HT patients (M = 223.18 AU/g prot) than in controls (M = 189.636 AU/g prot; p = 0.020) and inversely correlated with BAP levels (r = -0.196; p = 0.037). In uni- and multivariate analysis, serum antithyroperoxidase antibodies were the main predictors for d-ROMs (p = 0.006), BAP (p < 0.001), and AGEs (p = 0.014), irrespective of thyrotropin and/or free thyroxine values. No differences in AOPPs levels were found between patients and controls (p = 0.923). CONCLUSIONS: Oxidants are increased and antioxidants decreased in euthyroid HT patients. As a result, the oxidative/antioxidative balance is shifted toward the oxidative side. Moreover, this study reports on a possible significant involvement of AGEs in HT, thus contributing to a better definition of the redox homoeostasis dysregulation in HT. PMID- 26854842 TI - Polymorphic variation in CHAT gene modulates general cognitive ability: An association study with random student cohort. AB - The choline O-acetyltransferase (CHAT) gene has been associated with various human disorders that involve cognitive impairment or deficiency. However, the influence of disease-associated variants of CHAT on normal individuals remains dubious. Here we demonstrated the impact of CHAT sequence variants (G-120A) on general human cognitive ability in a cohort of 750 Chinese undergraduate students. A multiple choice questionnaire was used to obtain basic demographic information, such as parents' occupations and education levels. We also administered and scored the Raven's Standard Progressive Matrices (RSPM). A one way analysis of variance (ANOVA) and Kruskal-Wallis test (K-W) revealed a significant association between sequence polymorphisms of G-120A and individuals' Raven score (p=0.031 for ANOVA and p=0.026 for K-W tests). Moreover, further hierarchical analysis showed a similar trend in the association between G-120A variants and Raven scores only in the female subjects (p=0.008 for ANOVA and p=0.024 for K-W tests) but not in the male subjects. The results of a multiple linear regression confirmed that after we controlled gender, age, birthplace and other non-genetic factors, CHAT G-120A polymorphisms still significantly influenced individual Raven scores (B=-0.70, SE=0.28, t=-2.50, p=0.013). Our results demonstrated that sequence variants of CHAT were associated with human cognitive ability in not only patients with psychiatric disorders but also normal healthy individuals. However, some issues remained indeterminable, such as gender differences and the extent of the influence on individuals' general cognitive abilities; thus, the further research using an independent random sample was required. PMID- 26854841 TI - Expression of serotonin receptor genes in cranial ganglia. AB - Taste cells release neurotransmitters to gustatory neurons to transmit chemical information they received. Sweet, umami, and bitter taste cells use ATP as a neurotransmitter. However, ATP release from sour taste cells has not been observed so far. Instead, they release serotonin when they are activated by sour/acid stimuli. Thus it is still controversial whether sour taste cells use ATP, serotonin, or both. By reverse transcription-polymerase chain reaction and subsequent in situ hybridization (ISH) analyses, we revealed that of 14 serotonin receptor genes only 5-HT3A and 5-HT3B showed significant/clear signals in a subset of neurons of cranial sensory ganglia in which gustatory neurons reside. Double-fluorescent labeling analyses of ISH for serotonin receptor genes with wheat germ agglutinin (WGA) in cranial sensory ganglia of pkd1l3-WGA mice whose sour neural pathway is visualized by the distribution of WGA originating from sour taste cells in the posterior region of the tongue revealed that WGA-positive cranial sensory neurons rarely express either of serotonin receptor gene. These results suggest that serotonin receptors expressed in cranial sensory neurons do not play any role as neurotransmitter receptor from sour taste cells. PMID- 26854843 TI - Going round the bend: Persistent personal biases in walked angles. AB - For navigation through our environment, we can rely on information from various modalities, such as vision and audition. This information enables us for example to estimate our position relative to the starting position, or to integrate velocity and acceleration signals from the vestibular organ and proprioception to estimate the displacement due to self-motion. To better understand the mechanisms that underlie human navigation we analysed the performance of participants in an angle-walking task in the absence of visual and auditory signals. To this end, we guided them along paths of different lengths and asked them to turn by an angle of +/-90 degrees . We found significant biases in turn angles, i.e. systematic deviations from the correct angle and that these were characteristic for individual participants. Varying path length, however, had little effect on turn accuracy and precision. To check whether this idiosyncrasy was persistent over time and present in another type of walking task, we performed a second experiment several weeks later. Here, the same participants were guided to walk angles with varying amplitude. We then asked them to judge whether they had walked an angle larger or smaller than 90 degrees in a two-alternative forced choice paradigm. The personal bias was highly correlated between the two experiments even though they were conducted weeks apart. The presence of a persistent bias in walked angles in the absence of external directional cues indicates a possible error component for navigation, which is surprisingly time stable and idiosyncratic. PMID- 26854844 TI - Purslane Extract and Glucose Homeostasis in Adults with Type 2 Diabetes: A Double Blind, Placebo-Controlled Clinical Trial of Efficacy and Safety. AB - Purslane extract (PE) is derived from Portulaca oleracea L., a medicinal plant used in traditional medicine for its antidiabetic properties. This randomized, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of PE in improving glucose control, blood pressure, and lipid profile in adults with type 2 diabetes mellitus (T2DM) treated with a single oral hypoglycemic agent at baseline. Subjects were randomized to treatment with three capsules of PE/day or a matched placebo. Change from baseline to the week 12 end of-follow-up visit measures of glucose homeostasis, hemodynamics, and lipid profile was compared by treatment assignment. In addition, these measures were evaluated in a subgroup of "responders," defined as patients whose week 12 HbA1c was lower than baseline values, regardless of treatment assignment. This group was further assessed in subgroups of baseline oral hypoglycemic treatment. A total of 63 participants were treated with either PE (n = 31, 11 females, mean age 52.4 +/- 7.9 years) or matched placebo (n = 32, 11 females, mean age 58.3 +/- 10.8 years). In the total cohort, systolic blood pressure declined significantly more in the PE group than the placebo group: -7.5 +/- 5.0 versus -0.01 +/- 0.3 mmHg, P < .0001. In the responders' subgroup, HbA1c declined significantly more in the PE group than the placebo group: -0.8% +/- 0.4% versus -0.6% +/- 0.5%, P = .03. Few adverse events were reported. These were mild and did not differ by treatment assignment. PE appears to be a safe, adjunct treatment for T2DM, significantly reducing systolic blood pressure in the total cohort and HbA1c in the subgroup of responders. PMID- 26854845 TI - Chrysobalanus icaco L. Leaves Normalizes Insulin Sensitivity and Blood Glucose and Inhibits Weight Gain in High-Fat Diet-Induced Obese Mice. AB - Chrysobalanus icaco L. is a medicinal plant present in the Brazilian coastline and known for its hypoglicemic and antioxidant properties. Here, we assessed the beneficial metabolic effects of the aqueous extract of C. icaco (AECI) leaves in diet-induced obese mice. Swiss mice were fed standard chow (SC used as controls) or high-fat diet (HFD) to induce obesity. After 10 weeks, mice on each diet were divided into two groups with one group used as control while the other group treated with AECI for 4 weeks resulting in four groups of mice: SC; SC treated with AECI (SC + AECI); HFD; and HFD treated with AECI (HFD + AECI). AECI was administered drinking water at about 200 mg/kg. AECI was able to normalize insulin (13,682 +/- 1090 vs. 9828 +/- 485 AU, P < .05) and fasting blood glucose (192.8 +/- 14.2 vs. 132.3 +/- 6.4 mg/dL, P < .05) and inhibit weight gain (39 +/- 5.7%) and fat storage in liver (72.60 +/- 3.83%, P < .0001), despite the high-fat intake. These findings reinforce the use of AECI in hyperglycemia and highlight the potential extract's effect in preventing weight gain and fat accumulation in liver of diet-induced obese mice. PMID- 26854846 TI - Potential Therapeutic Applications of Mucuna pruriens Peptide Fractions Purified by High-Performance Liquid Chromatography as Angiotensin-Converting Enzyme Inhibitors, Antioxidants, Antithrombotic and Hypocholesterolemic Agents. AB - A Mucuna pruriens protein concentrate was hydrolyzed with a digestive (pepsin pancreatin) enzymatic system. The soluble portion of the hydrolysate was fractionated by ultrafiltration and the ultrafiltered peptide fraction (PF) with lower molecular weight was purified by reversed-phase high-performance liquid chromatography. The PF obtained were evaluated by testing the biological activity in vitro. Fractions showed that the ability to inhibit the angiotensin-converting enzyme had IC50 values that ranged from 2.7 to 6.2 MUg/mL. Trolox equivalent antioxidant capacity values ranged from 132.20 to 507.43 mM/mg. The inhibition of human platelet aggregation ranged from 1.59% to 11.11%, and the inhibition of cholesterol micellar solubility ranged from 0.24% to 0.47%. Hydrophobicity, size, and amino acid sequence could be factors in determining the biological activity of peptides contained in fractions. This is the first report that M. pruriens peptides act as antihypertensives, antioxidants, and inhibitors for human platelet aggregation and cholesterol micellar solubility in vitro. PMID- 26854847 TI - Pharmacokinetics and Plasma Cellular Antioxidative Effects of Flavanols After Oral Intake of Green Tea Formulated with Vitamin C and Xylitol in Healthy Subjects. AB - This study aimed to test whether green tea formulated with vitamin C and xylitol (GTVX) could improve absorption of flavanols and total antioxidant activity (TAC) of plasma compared with green tea only (GT) in healthy subjects. The total radical-trapping antioxidant parameter method was used to measure the TAC of plasma. Cmax, Tmax, and area under the curve (AUC) of flavanols in plasma after consumption of GTVX were 5980.58 MUg/mL, 2.14 h, and 18,915.56 h.MUg/mL, respectively, indicating that GTVX showed significantly higher AUC than GT (13,855.43 MUg/mL). The peak TACs occurred at 3 and 0.5 h after intake of GT and GTVX, respectively. The TAC of plasma was found to be significantly higher in GTVX than in GT at each time point. This study suggests that formulating green tea with vitamin C and xylitol could increase the absorption of flavanols in green tea, enhancing cellular antioxidative effects. PMID- 26854848 TI - DELLA Proteins Promote Anthocyanin Biosynthesis via Sequestering MYBL2 and JAZ Suppressors of the MYB/bHLH/WD40 Complex in Arabidopsis thaliana. AB - Anthocyanin accumulation is recognized as a visible biomarker of plants that have suffered from environmental stresses. However, the molecular mechanisms underlying stress-induced anthocyanin biosynthesis remain unclear. Expression of anthocyanin-specific genes is regulated by the conserved MBW complex, which is composed of the MYB, bHLH, and WD40 subunits in higher plants. MBW activity is repressed by MYBL2 and the JAZ family proteins, which bind competitively to bHLH and MYB/bHLH, respectively. Here, we found that MYBL2 and JAZs mediate gibberellic acid-inhibited anthocyanin biosynthesis in Arabidopsis. Competitive pull-down and dual-luciferase assays showed that DELLA proteins directly sequester MYBL2 and JAZ repressors, leading to the release of bHLH/MYB subunits and subsequently to the formation of active MBW complex, which then activates the anthocyanin biosynthetic pathway. The JAZ-DELLA-MYBL2 module also plays an important role in abiotic stress-induced anthocyanin biosynthesis. Furthermore, we found that the DELLA protein RGA accumulates upon plant exposure to abiotic stresses. Altogether, our data reveal that DELLA-promoted anthocyanin biosynthesis is mediated at least in part by MYBL2 and JAZ regulatory proteins, providing new insights into the coordinated regulation of plant growth and defense through metabolic pathway regulation. PMID- 26854849 TI - Transcriptional and Post-transcriptional Modulation of SQU and KEW Activities in the Control of Dorsal-Ventral Asymmetric Flower Development in Lotus japonicus. AB - In Papilionoideae legume, Lotus japonicus, the development of dorsal-ventral (DV) asymmetric flowers is mainly controlled by two TB1/CYCLOIDEA/PCF (TCP) genes, SQUARED STANDARD (SQU) and KEELED WINGS IN LOTUS (KEW), which determine dorsal and lateral identities, respectively. However, the molecular basis of how these two highly homologous genes orchestrate their diverse functions remains unclear. Here, we analyzed their expression levels, and investigated the transcriptional activities of SQU and KEW. We demonstrated that SQU possesses both activation and repression activities, while KEW acts only as an activator. They form homo- and heterodimers, and then collaboratively regulate their expression at the transcription level. Furthermore, we identified two types of post-transcriptional modifications, phosphorylation and ATP/GTP binding, both of which could affect their transcriptional activities. Mutations in ATP/GTP binding motifs of SQU and KEW lead to failure of phosphorylation, and transgenic plants bearing the mutant proteins display defective DV asymmetric flower development, indicating that the two conjugate modifications are essential for their diverse functions. Altogether, SQU and KEW activities are precisely modulated at both transcription and post-transcription levels, which might link DV asymmetric flower development to different physiological status and/or signaling pathways. PMID- 26854850 TI - Direct Y-STR amplification of body fluids deposited on commonly found crime scene substrates. AB - Body fluids detected on commonly found crime scene substrates require extraction, purification and quantitation of DNA prior to amplification and generation of short tandem repeat (STR) DNA profiles. In this research Y-STR profiles were generated via direct amplification of blood and saliva deposited on 12 different substrates. These included cigarette butts, straws, grass, leaves, woodchips and seven different types of fabric. After depositing either 0.1 MUL of blood or 0.5 MUL of saliva, each substrate containing the dry body fluid stain was punched using a Harris 1.2 mm micro-punch. Each of these punched substrates, a total of 720 samples, containing minute amount of blood or saliva was either amplified directly without any pre-treatment, or was treated with one of the four washing reagents or buffer. In each of these five experimental groups the substrates containing the body fluid remained in the amplification reagent during the thermal cycling process. Each sample was amplified with the three direct Y-STR amplification kits; AmpFlSTR((r)) Yfiler((r)) Direct, Yfiler((r)) Plus Amplification Kits and the PowerPlex((r)) Y23 System. Complete and concordant Y STR profiles were successfully obtained from most of these 12 challenging crime scene objects when the stains were analyzed by at least one of the five experimental groups. The reagents and buffer were interchangeable among the three amplification kits, however, pre-treatment with these solutions did not appear to enhance the quality or the number of the full profiles generated with direct amplification. This study demonstrates that blood and saliva deposited on these simulated crime scene objects can be amplified directly. PMID- 26854851 TI - Incidence of fatal snake bite in Loni, Maharashtra: An autopsy based retrospective study (2004-2014). AB - Snake bite is a major public health problem specially in a rural region where agricultural work is the major source of employment. A retrospective study was undertaken of all cases of deaths due to snake bite autopsied at the Mortuary of Pravara Rural Hospital, Loni a rural area in Western Maharashtra over a period of 10 years from January 2004 to December 2014. Data of the study was gathered from autopsy reports and hospital records. The cases represented approximately 2.13% (54) of the total 2539 medico legal autopsies conducted during the study period. Most of the deaths (42.60%) occurred in the age group of 11-30 years and both males and females were affected in almost equal proportions. There was a marked increase in the number of cases in monsoon season (59.26%). The lower extremity was the most frequently involved site of bite (62.96%). Snakes were identified in 43 cases (79.63%) and among the identified cases the most common culprit was Viper amounting to 29.63% of cases followed by Krait causing 24.07% of the deaths. The findings in our study reflects the necessity of educating the rural community regarding the hazards of snake bite, importance of early medical attention and to avoid wasting vital time being engaged by traditional healers. PMID- 26854852 TI - Medico legal and epidemiological aspects of femicide in a judicial district of north eastern Italy. AB - Femicide is the intentional killing of a woman because she is female, and often occurs when there are pre-existing relations, intimate or otherwise, between the victim and the murderer. A retrospective epidemiological study was made of 34 female homicides recorded in a university departmental register of post-mortems, pertaining to a judicial district of about 700,000 inhabitants in north eastern Italy, during a 21-year period from January 1st 1993 to December 31st 2013. The temporal trend, the socio-demographic characteristics of victims and perpetrators, the circumstances surrounding the crime and the risk factors for femicide were studied with the aim of identifying and developing preventive strategies. PMID- 26854853 TI - The importance of hair testing in GHB facilitated sexual assault cases. PMID- 26854854 TI - Heart-type fatty acid binding protein and cardiac troponin I may have a diagnostic value in electrocution: A rat model. AB - Although cardiac injury is known to be the leading cause of death in electrocution, the differential diagnosis can be challenging in forensic practice since the exact mechanism is poorly understood and there is lack of reliable markers. Thus, death due to electrocution may be classified as a negative autopsy. The serum levels of and myocardial immunostaining loss for cardiac troponins and heart-type fatty acid binding protein (H-FABP) are highly sensitive and specific biomarkers of ischemic myocardial damage and may have a diagnostic value in determining the myocardial injury or the cause of death due to electrocution. Due to this reason, a rat model is prepared to investigate these issues. Thirty-two Wistar albino female rats were included and randomly divided into four groups of eight subjects. Group A was the control group, and Group B, C, and D were exposed to electrical current of 110 volt (V), 220 V, and 600 V, respectively. Blood samples and the hearts were collected from the rats for biochemical and immunostaining analyses. It is found that increased serum H-FABP levels were significantly associated with the higher voltage immediately after electrocution. However, serum cardiac troponin I (cTnI) levels did not show significant changes associated with the higher voltage in the early period of electrocution. As for histopathological examinations, the only significant difference in myocardial immunostaining loss was for H-FABP in Group B. Serum H FABP levels may have a diagnostic value in the early postmortem period immediately after electrocution. Besides, it seems that serum H-FABP levels may be a better indicator than those of cTnI to reflect the myocardial damage in the early period of the electrocution. PMID- 26854855 TI - Role of Environmental Factors on Resuming Valued Activities Poststroke: A Systematic Review of Qualitative and Quantitative Findings. AB - OBJECTIVE: To investigate how reengagement in valued activities poststroke is influenced by environmental factors. DATA SOURCES: PubMed, CINAHL, and PsycINFO were searched to June 2015 using multiple search terms for stroke, activities, disability, and home and community environments, with the following constraints: English, humans, and adults. STUDY SELECTION: Studies were included that contained data on how reengagement in valued activities of community-dwelling stroke survivors was influenced by the environment. Two reviewers independently selected the studies. The search yielded 3726 records; 39 studies were eventually included. DATA EXTRACTION: Findings were extracted from qualitative, quantitative, and mixed-design studies. Two reviewers independently assessed study quality using the Oxford Critical Appraisal Skills Programme lists and independently extracted results. DATA SYNTHESIS: Thematic analysis was conducted on qualitative data, revealing 9 themes related to the iterative nature of the process of reengagement and the associated environmental factors. During the process of reengagement, environmental factors interact with personal and disease related factors in a gradual process of shaping or abandoning valued activities. The sociocultural context in this case determines what activities are valued and can be resumed by stroke survivors. Social support; activity opportunities and obligations; familiar and accessible environments; resources and reminders; and a step-by-step return facilitate stroke survivors to explore, adapt, resume, and maintain their activities. Social support is helpful at all stages of the process and particularly is important in case stroke survivors are fearful to explore their activity possibilities. The quantitative data identified largely endorsed these findings. No quantitative data were found in respect to the iterative nature of the process, familiar environments, or accessibility. CONCLUSIONS: Reengagement in valued activities is a gradual process. In each stage of the process, several environmental factors play a role. During rehabilitation, professionals should pay attention to the role physical and social environmental factors have in reengagement poststroke and find ways to optimize stroke survivors' environments. PMID- 26854856 TI - Resilience, Pain Interference, and Upper Limb Loss: Testing the Mediating Effects of Positive Emotion and Activity Restriction on Distress. AB - OBJECTIVE: To test mediating effects of positive emotion and activity restriction on the associations of resilience and pain interference with distress reported by individuals with traumatic upper limb loss evaluated for prosthetics. DESIGN: Cross-sectional correlational study of several demographic and self-report measures of resilience, pain interference, activity restriction, positive emotions, and symptoms of depression and posttraumatic stress. SETTING: Six regional centers throughout the United States. PARTICIPANTS: A total of 263 prospective participants consented to be evaluated for eligibility and need for upper extremity prosthetics; participants (N=202; 57 women [28.2%] and 145 men [71.8%]; mean age, 41.81+/-14.83y; range, 18.01-72.95y) who sustained traumatic injuries were retained in this study. Most of them were identified as white (70.8%; n=143), followed by black (10.4%; n=21), Hispanic (9.9%; n=20), Asian (3.0%; n=6), other (1.5%; n=3), and missing (4.5%; n=9). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary Care Posttraumatic Stress Disorder Screen and depression screen. RESULTS: Resilience and pain interference were significantly correlated in predicted directions with positive emotions, activity restriction, and the 2 distress variables. A path model revealed that the associations of resilience and pain interference with both distress variables were completely mediated by positive emotions and activity restriction. There were no significant direct effects of resilience or pain interference on either distress variable. CONCLUSIONS: Resilience may facilitate adjustment via beneficial and predicted associations with positive emotions and active engagement with the environment. These relations are independent of the significant and inverse associations of pain interference with these same variables. Longitudinal research is needed to understand interactions between positive emotions and activity over time in promoting adjustment after traumatic limb loss. Individuals reporting depression and/or posttraumatic stress disorder symptoms may require interventions that reduce avoidance and promote activities that may increase the likelihood of experiencing positive emotions. PMID- 26854858 TI - Evolution of electronic waste toxicity: Trends in innovation and regulation. AB - Rapid innovation in printed circuit board, and the uncertainties surrounding quantification of the human and environmental health impacts of e-waste disposal have made it difficult to confirm the influence of evolving e-waste management strategies and regulatory policies on materials. To assess these influences, we analyzed hazardous chemicals in a market-representative set of Waste printed circuit boards (WPCBs, 1996-2010). We used standard leaching tests to characterize hazard potential and USEtox(r) to project impacts on human health and ecosystem. The results demonstrate that command-and-control regulations have had minimal impacts on WPCBs composition and toxicity risks; whereas technological innovation may have been influenced more by resource conservation, including a declining trend in the use of precious metals such as gold. WPCBs remain classified as hazardous under U.S. and California laws because of excessive toxic metals. Lead poses the most significant risk for cancers; zinc for non-cancer diseases; copper had the largest potential impact on ecosystem quality. Among organics, acenaphthylene, the largest risk for cancers; naphthalene for non-cancer diseases; pyrene has the highest potential for ecotoxicological impacts. These findings support the need for stronger enforcement of international policies and technology innovation to implement the strategy of design-for-the-environment and to encourage recovery, recycling, and reuse of WPCBs. PMID- 26854857 TI - FusX: A Rapid One-Step Transcription Activator-Like Effector Assembly System for Genome Science. AB - Transcription activator-like effectors (TALEs) are extremely effective, single molecule DNA-targeting molecular cursors used for locus-specific genome science applications, including high-precision molecular medicine and other genome engineering applications. TALEs are used in genome engineering for locus-specific DNA editing and imaging, as artificial transcriptional activators and repressors, and for targeted epigenetic modification. TALEs as nucleases (TALENs) are effective editing tools and offer high binding specificity and fewer sequence constraints toward the targeted genome than other custom nuclease systems. One bottleneck of broader TALE use is reagent accessibility. For example, one commonly deployed method uses a multitube, 5-day assembly protocol. Here we describe FusX, a streamlined Golden Gate TALE assembly system that (1) is backward compatible with popular TALE backbones, (2) is functionalized as a single-tube 3-day TALE assembly process, (3) requires only commonly used basic molecular biology reagents, and (4) is cost-effective. More than 100 TALEN pairs have been successfully assembled using FusX, and 27 pairs were quantitatively tested in zebrafish, with each showing high somatic and germline activity. Furthermore, this assembly system is flexible and is compatible with standard molecular biology laboratory tools, but can be scaled with automated laboratory support. To demonstrate, we use a highly accessible and commercially available liquid-handling robot to rapidly and accurately assemble TALEs using the FusX TALE toolkit. Together, the FusX system accelerates TALE-based genomic science applications from basic science screening work for functional genomics testing and molecular medicine applications. PMID- 26854860 TI - How Does Hyperphopsphorylation Promote Tau Aggregation and Modulate Filament Structure and Stability? AB - Tau proteins are hyperphosphorylated at common sites in their N- and C-terminal domains in at least three neurodegenerative diseases, Parkinson, dementia with Lewy bodies, and Alzheimer's, suggesting specific pathology but general mechanism. Full-length human tau filament comprises a rigid core and a two layered fuzzy coat. Tau is categorized into two groups of isoforms, with either four repeats (R1-R4) or three repeats (R1, R3, and R4); their truncated constructs are respectively called K18 and K19. Using multiscale molecular dynamics simulations, we explored the conformational consequences of hyperhposphorylation on tau's repeats. Our lower conformational energy filament models suggest a rigid filament core with a radius of ~30 to 40 A and an outer layer with a thickness of ~140 A consisting of a double-layered polyelectrolyte. The presence of the phosphorylated terminal domains alters the relative stabilities in the K18 ensemble, thus shifting the populations of the full-length filaments. However, the structure with the straight repeats in the core region is still the most stable, similar to the truncated K18 peptide species without the N and C-terminus. Our simulations across different scales of resolution consistently reveal that hyperphosphorylation of the two terminal domains decreases the attractive interactions among the N- and C-terminus and repeat domain. To date, the relationship on the conformational level between phosphorylation and aggregation has not been understood. Our results suggest that the exposure of the repeat domain upon hyperphosphorylation could enhance tau filament aggregation. Thus, we discovered that even though these neurodegenerative diseases vary and their associated tau filaments are phosphorylated to different extents, remarkably, the three pathologies appear to share a common tau aggregation mechanism. PMID- 26854859 TI - Inhibition of CD73 AMP hydrolysis by a therapeutic antibody with a dual, non competitive mechanism of action. AB - CD73 (ecto-5'-nucleotidase) has recently been established as a promising immuno oncology target. Given its role in activating purinergic signaling pathways to elicit immune suppression, antagonizing CD73 (i.e., releasing the brake) offers a complimentary pathway to inducing anti-tumor immune responses. Here, we describe the mechanistic activity of a new clinical therapeutic, MEDI9447, a human monoclonal antibody that non-competitively inhibits CD73 activity. Epitope mapping, structural, and mechanistic studies revealed that MEDI9447 antagonizes CD73 through dual mechanisms of inter-CD73 dimer crosslinking and/or steric blocking that prevent CD73 from adopting a catalytically active conformation. To our knowledge, this is the first report of an antibody that inhibits an enzyme's function through 2 distinct modes of action. These results provide a finely mapped epitope that can be targeted for selective, potent, and non-competitive inhibition of CD73, as well as establish a strategy for inhibiting enzymes that function in both membrane-bound and soluble states. PMID- 26854861 TI - Anti-apoptotic effects of myocardin-related transcription factor-A on rat cardiomyocytes following hypoxia-induced injury. AB - Myocardin-related transcription factor-A (MRTF-A) can transduce both biomechanical and humoral signals, which can positively modulate cardiac damage induced by acute myocardial infarction. However, the molecular mechanism that underlies the contribution that MRTF-A provides to the myocardium is not completely understood. The objective of this study was to investigate the effects of MRTF-A on myocardium apoptosis and its mechanisms. Our experiment results showed that MRTF-A expression increased and Bcl-2 expression reduced during myocardial ischemia-reperfusion in rat. Meanwhile, primary cardiomyocytes were pretreated with wild-type MRTF-A or siRNA of MRTF-A before exposure to hypoxia. We found that overexpression of MRTF-A in myocardial cells inhibited apoptosis and the release of cytochrome c. MRTF-A enhanced Bcl-2, which contributes to MRTF A interaction with Bcl-2 in the nuclei of cardiomyocytes. MRTF-A upregulation expression of Bcl-2 in cardiomyocytes induced by hypoxia was inhibited by PD98059, an ERK1/2 inhibitor. In conclusions, MRTF-A improved myocardial cell survival in a cardiomyocyte model of hypoxia-induced injury; this effect was correlated with the upregulation of anti-apoptotic gene Bcl-2 through the activation of ERK1/2. PMID- 26854862 TI - Pharmaceutical formulation of HSA hybrid coated iron oxide nanoparticles for magnetic drug targeting. AB - In this work we present a new formulation of superparamagnetic iron oxide nanoparticles (SPIONs) for magnetic drug targeting. The particles were reproducibly synthesized from current good manufacturing practice (cGMP) - grade substances. They were surface coated using fatty acids as anchoring molecules for human serum albumin. We comprehensively characterized the physicochemical core shell structure of the particles using sophisticated methods. We investigated biocompatibility and cellular uptake of the particles using an established flow cytometric method in combination with microwave-plasma assisted atomic emission spectroscopy (MP-AES). The cytotoxic drug mitoxantrone was adsorbed on the protein shell and we showed that even in complex media it is slowly released with a close to zero order kinetics. We also describe an in vitro proof-of-concept assay in which we clearly showed that local enrichment of this SPION-drug conjugate with a magnet allows site-specific therapeutic effects. PMID- 26854863 TI - C8orf37 is mutated in Bardet-Biedl syndrome and constitutes a locus allelic to non-syndromic retinal dystrophies. AB - Bardet-Biedl syndrome (BBS) is a pleiotropic and clinically and genetically heterogeneous ciliopathy. Primary features are early-onset retinal dystrophy that is typically rod-cone, obesity, polydactyly, renal abnormalities, hypogonadism, and learning difficulties, but most patients do not present with the full clinical picture. In a BBS patient from a consanguineous marriage we performed next-generation sequencing targeting all known BBS genes and other genes known or hypothesized to cause ciliopathies. While no mutation was present in any of the recognized genes for BBS, we were able to identify the homozygous non conservative mutation c.529C>T (p.Arg177Trp) in C8orf37 that segregated with the phenotype, affects an evolutionarily highly conserved residue, and is bioinformatically predicted to be pathogenic. The same mutation has been described in unrelated patients with non-syndromic cone-rod dystrophy and other C8orf37 changes were found in individuals with retinitis pigmentosa. We conclude that C8orf37 should be added to BBS screening panels as a probable rare cause of the disease and that individuals with C8orf37-related retinal dystrophy should be screened for BBS features. PMID- 26854864 TI - Energy of the Lowest Unoccupied Molecular Orbital, Thiol Reactivity, and Toxicity of Three Monobrominated Water Disinfection Byproducts. AB - Disinfection of drinking water protects public health against waterborne pathogens. However, during disinfection, toxic disinfection byproducts (DBPs) are formed. Exposure to DBPs was associated with increased risk of bladder cancer in humans. DBPs are generated at concentrations below their carcinogenic potencies; it is unclear how exposure leads to adverse health outcomes. We used computational estimates of the energy of the lowest unoccupied molecular orbital (ELUMO) to predict thiol reactivity and additive toxicity among soft electrophile DBPs. Bromoacetic acid (BAA) was identified as non-thiol-reactive, which was supported by in chemico and in vitro data. Bromoacetonitrile (BAN) and bromoacetamide (BAM) were thiol-reactive. Genotoxicity induced by these compounds was reduced by increasing the thiol pool with N-acetyl L-cysteine (NAC), while NAC had little effect on BAA. BAN and BAM shared depletion of glutathione (GSH) or cellular thiols as a molecular initiating event (MIE), whereas BAA induces toxicity through another pathway. Binary mixtures of BAM and BAN expressed a potentiating effect in genotoxicity. We found that soft electrophile DBPs could be an important predictor of common mechanism groups that demonstrated additive toxicity. In silico estimates of ELUMO could be used to identify the most relevant DBPs that are the forcing factors of the toxicity of finished drinking waters. PMID- 26854865 TI - Homologation Reaction of Ketones with Diazo Compounds. AB - This review covers the addition of diazo compounds to ketones to afford homologated ketones, either in the presence or in the absence of promoters or catalysts. Reactions with diazoalkanes, aryldiazomethanes, trimethylsilyldiazomethane, alpha-diazo esters, and disubstituted diazo compounds are covered, commenting on the complex regiochemistry of the reaction and the nature of the catalysts and promoters. The recent reports on the enantioselective version of ketone homologation reactions are gathered in one section, followed by reports on the use of cyclic ketones ring expansion in total synthesis. Although the first reports of this reaction appeared in the literature almost one century ago, the recent achievements, in particular, for the asymmetric version, forecast the development of new breakthroughs in the synthetically valuable field of diazo chemistry. PMID- 26854867 TI - Parsing fear: A reassessment of the evidence for fear deficits in psychopathy. AB - Psychopathy is a personality disorder characterized by interpersonal manipulation and callousness, and reckless and impulsive antisocial behavior. It is often seen as a disorder in which profound emotional disturbances lead to antisocial behavior. A lack of fear in particular has been proposed as an etiologically salient factor. In this review, we employ a conceptual model in which fear is parsed into separate subcomponents. Important historical conceptualizations of psychopathy, the neuroscientific and empirical evidence for fear deficits in psychopathy are compared against this model. The empirical evidence is also subjected to a meta-analysis. We conclude that most studies have used the term "fear" generically, amassing different methods and levels of measurement under the umbrella term "fear." Unlike earlier claims that psychopathy is related to general fearlessness, we show there is evidence that psychopathic individuals have deficits in threat detection and responsivity, but that the evidence for reduced subjective experience of fear in psychopathy is far less compelling. (PsycINFO Database Record PMID- 26854868 TI - A method for using real world data in breast cancer modeling. AB - OBJECTIVES: Today, hospitals and other health care-related institutions are accumulating a growing bulk of real world clinical data. Such data offer new possibilities for the generation of disease models for the health economic evaluation. In this article, we propose a new approach to leverage cancer registry data for the development of Markov models. Records of breast cancer patients from a clinical cancer registry were used to construct a real world data driven disease model. METHODS: We describe a model generation process which maps database structures to disease state definitions based on medical expert knowledge. Software was programmed in Java to automatically derive a model structure and transition probabilities. We illustrate our method with the reconstruction of a published breast cancer reference model derived primarily from clinical study data. In doing so, we exported longitudinal patient data from a clinical cancer registry covering eight years. The patient cohort (n=892) comprised HER2-positive and HER2-negative women treated with or without Trastuzumab. RESULTS: The models generated with this method for the respective patient cohorts were comparable to the reference model in their structure and treatment effects. However, our computed disease models reflect a more detailed picture of the transition probabilities, especially for disease free survival and recurrence. CONCLUSIONS: Our work presents an approach to extract Markov models semi-automatically using real world data from a clinical cancer registry. Health care decision makers may benefit from more realistic disease models to improve health care-related planning and actions based on their own data. PMID- 26854869 TI - Isolation of novel variants of infectious bursal disease virus from different outbreaks in Northeast India. AB - Infectious bursal disease virus (IBDV) is a highly infectious disease of young chicken that predominantly affects the immune system. In the present study, we are reporting first comprehensive study of IBDV outbreaks from the Northeastern part of India. Northeast India shares a porous border with four different countries; and as a rule any outbreak in the neighboring countries substantially affects the poultry population in the adjoining states. Nucleotide sequence analysis of the VP2 gene of the IBDV isolates from the Northeastern part of India suggested the extreme virulent nature of the virus. The virulent marker amino acids (A222, I242, Q253, I256 and S299) in the hypervariable region of the Northeastern isolates were found identical with the reported very virulent strains of IBDV. A unique insertion of I/L294V was recorded in all the isolates of the Northeastern India. The study will be useful in understanding the circulating pathotypes of IBDV in India. PMID- 26854870 TI - Liquid Marbles Stabilized by Fluorine-Bearing Cyclomatrix Polyphosphazene Particles and Their Application as High-Efficiency Miniature Reactors. AB - Increasing attention has been paid to fabricate multifunctional stabilizers of liquid marbles for expanding their application. Here, a kind of hydrophobic cyclomatrix polyphosphazene particles (PZAF) were facilely prepared using a one step precipitation polycondensation of hexachlorocyclotriphosphazene and 4,4' (hexafluoroisopropylidene)diphenol, and their ability to stabilize liquid marbles was first investigated. The Ag nanoparticle-decorated PZAF particles (Ag/PZAF) were then fabricated by an in situ reduction of silver nitrate onto PZAF particles and used to construct catalytic liquid marbles. The results revealed that the reduction of methylene blue (MB) in aqueous solution by sodium borohydride could be highly efficiently catalyzed in the catalytic liquid marbles, even with a large volume. An excellent cycle use performance of the catalytic liquid marbles without losing catalytic efficiency was also present. The high catalytic activity is mainly attributed to the uniform immobilization of Ag nanoparticles onto PZAF particles and the adsorption behavior of PZAF particles toward MB, which may play an effect on allowing high catalytic surface area and effective accelerating the mass transfer of MB to the Ag catalytic active sites, respectively. Therefore, the combination of Ag nanoparticles with PZAF particles has been demonstrated clearly to be a facile and effective strategy to obtain the functional stabilizer for preparing the catalytic liquid marbles as promising miniature reactors used in heterogeneous catalytic reactions. PMID- 26854866 TI - Neural vulnerability factors that increase risk for future weight gain. AB - Theorists have proposed several neural vulnerability factors that may increase overeating and consequent weight gain. Early cross-sectional imaging studies could not determine whether aberrant neural responsivity was a precursor or consequence of overeating. However, recent prospective imaging studies examining predictors of future weight gain and response to obesity treatment, and repeated measures imaging studies before and after weight gain and loss have advanced knowledge of etiologic processes and neural plasticity resulting from weight change. The present article reviews evidence from prospective studies using imaging and behavioral measures reflecting neural function, as well as randomized experiments with humans and animals that are consistent or inconsistent with 5 neural vulnerability theories for excessive weight gain. Extant data provide strong support for the incentive sensitization theory of obesity and moderate support for the reward surfeit theory, inhibitory control deficit theory, and dynamic vulnerability model of obesity, which attempted to synthesize the former theories into a single etiologic model. However, existing data provide only minimal support for the reward deficit theory. Findings are synthesized into a new working etiologic model that is based on current scientific knowledge. Important directions for future studies, which have the potential to support or refute this working etiologic model, are delineated. (PsycINFO Database Record PMID- 26854871 TI - Synthesis of Pyridone-based Nucleoside Analogues as Substrates or Inhibitors of DNA Polymerases. AB - The synthesis and characterization of novel acyclic and cyclic pyridone-based nucleosides and nucleotides is described. In total, seven nucleosides and four nucleotides were synthesized. None of the tested nucleosides showed inhibitory properties against Klenow exo- polymerase and M.MuLV and HIV-1 reverse transcriptases. The nucleotides containing 4-chloro- and 4-bromo-2-pyridone as a nucleobase were accepted by the Klenow fragment, but at the expense of fidelity and extension efficiency. PMID- 26854872 TI - Toxicity and transfer of polyvinylpyrrolidone-coated silver nanowires in an aquatic food chain consisting of algae, water fleas, and zebrafish. AB - Nanomaterials of various shapes and dimensions are widely used in the medical, chemical, and electronic industries. Multiple studies have reported the ecotoxicological effects of nanaoparticles when released in aquatic and terrestrial ecosystems; however, information on the toxicity of silver nanowires (AgNWs) to freshwater organisms and their transfer through the food webs is limited. In the present study, we aimed to evaluate the toxicity of 10- and 20 MUm-long AgNWs to the alga Chlamydomonas reinhardtii, the water flea Daphnia magna, and the zebrafish and study their movement through this three-species food chain using a variety of qualitative and quantitative methods as well as optical techniques. We found that AgNWs directly inhibited the growth of algae and destroyed the digestive organs of water fleas. The results showed that longer AgNWs (20MUm) were more toxic than shorter ones (10MUm) to both algae and water fleas, but shorter AgNWs were accumulated more than longer ones in the body of the fish. Overall, this study suggests that AgNWs are transferred through food chains, and that they affect organisms at higher trophic levels, potentially including humans. Therefore, further studies that take into account environmental factors, food web complexity, and differences between nanomaterials are required to gain better understanding of the impact of nanomaterials on natural communities and human health. PMID- 26854873 TI - Eurotransplant donor-risk-index and recipient factors: influence on long-term outcome after liver transplantation - A large single-center experience. AB - The organ shortage has led to increased use of marginal organs. The Eurotransplant Donor-Risk-Index (ET-DRI) was established to estimate outcome after Liver Transplantation (LT). Currently, data on impact of ET-DRI on long term outcome for different indications and recipient conditions are missing. Retrospective, single-center analysis of long-term graft survival (GS) of 1767 adult primary LTs according to indication, labMELDcategory (1: <=18; 2: >18-25; 3: >25-35; 4: >35), and ET-DRI. Mean ET-DRI in our cohort was 1.63 (+/-0.43). One , 10, and 15-yr GS was 83.5%, 63.3%, and 54.8%. Long-term GS was significantly influenced by ET-DRI. Accordingly, four ET-DRI categories were defined and analyzed with respect to underlying disease. Significant impact of these categories was observed for: Alcohol, cholestatic/autoimmune diseases (CD/AIH), and HCV, but not for HCC, HBV, cryptogenic cirrhosis, and acute liver failure. labMELD categories showed no significant influence on graft, but on patient survival. Matching ET-DRI categories with labMELD revealed significant differences in long-term GS for labMELDcategories 1, 2, and 3, but not 4. In multivariate analysis, HCV combined with ET-DRI > 2 and labMELDcategory 3 combined with ET-DRI > 2 emerged as negative predictors. To achieve excellent long-term graft survival, higher risk organs (ET-DRI > 1.4) should be used restrictively for patients with CD/AIH or HCV. Organs with ET-DRI > 2 should be avoided in patients with a labMELD of >25-35. PMID- 26854874 TI - Efficient and Flexible Computation of Many-Electron Wave Function Overlaps. AB - A new algorithm for the computation of the overlap between many-electron wave functions is described. This algorithm allows for the extensive use of recurring intermediates and thus provides high computational efficiency. Because of the general formalism employed, overlaps can be computed for varying wave function types, molecular orbitals, basis sets, and molecular geometries. This paves the way for efficiently computing nonadiabatic interaction terms for dynamics simulations. In addition, other application areas can be envisaged, such as the comparison of wave functions constructed at different levels of theory. Aside from explaining the algorithm and evaluating the performance, a detailed analysis of the numerical stability of wave function overlaps is carried out, and strategies for overcoming potential severe pitfalls due to displaced atoms and truncated wave functions are presented. PMID- 26854875 TI - Measuring epistasis in fitness landscapes: The correlation of fitness effects of mutations. AB - Genotypic fitness landscapes are constructed by assessing the fitness of all possible combinations of a given number of mutations. In the last years, several experimental fitness landscapes have been completely resolved. As fitness landscapes are high-dimensional, simple measures of their structure are used as statistics in empirical applications. Epistasis is one of the most relevant features of fitness landscapes. Here we propose a new natural measure of the amount of epistasis based on the correlation of fitness effects of mutations. This measure has a natural interpretation, captures well the interaction between mutations and can be obtained analytically for most landscape models. We discuss how this measure is related to previous measures of epistasis (number of peaks, roughness/slope, fraction of sign epistasis, Fourier-Walsh spectrum) and how it can be easily extended to landscapes with missing data or with fitness ranks only. Furthermore, the dependence of the correlation of fitness effects on mutational distance contains interesting information about the patterns of epistasis. This dependence can be used to uncover the amount and nature of epistatic interactions in a landscape or to discriminate between different landscape models. PMID- 26854876 TI - Adaptive threshold harvesting and the suppression of transients. AB - Fluctuations in population size are in many cases undesirable, as they can induce outbreaks and extinctions or impede the optimal management of populations. We propose the strategy of adaptive threshold harvesting (ATH) to control fluctuations in population size. In this strategy, the population is harvested whenever population size has grown beyond a certain proportion in comparison to the previous generation. Taking such population increases into account, ATH intervenes also at smaller population sizes than the strategy of threshold harvesting. Moreover, ATH is the harvesting version of adaptive limiter control (ALC) that has recently been shown to stabilize population oscillations in both experiments and theoretical studies. We find that ATH has similar stabilization properties as ALC and thus offers itself as a harvesting alternative for the control of pests, exploitation of biological resources, or when restocking interventions required from ALC are unfeasible. We present numerical simulations of ATH to illustrate its performance in the presence of noise, lattice effect, and Allee effect. In addition, we propose an adjustment to both ATH and ALC that restricts interventions when control seems unnecessary, i.e. when population size is too small or too large, respectively. This adjustment cancels prolonged transients. PMID- 26854877 TI - Effect of prosthetic restoration on masticatory function in patients with shortened dental arches: a multicentre study. AB - The aim of this multicentre study was to investigate the effect of prosthetic restoration for missing posterior teeth on mastication in patients with shortened dental arches (SDAs). Partially dentate patients who had an intact teeth in anterior region and missed distal molar(s) (2-12 missing occlusal units) classified as Kennedy Class I or Class II were recruited from seven university based dental hospitals in Japan. Of the 125 subjects who underwent baseline (pre treatment) and follow-up/post-treatment evaluation, 53 chose no replacement of missing teeth and 72 chose treatment with removable partial dentures (n = 53) or implant-supported fixed partial dentures (n = 19). Objective masticatory performance (MP) was evaluated using a gummy jelly test. Perception of chewing ability (CA) was rated using a food intake questionnaire. In the no-treatment group, mean MP and CA scores at baseline were similar to those at follow-up evaluation (P > 0.05). In the treatment group, mean MP after treatment was significantly greater than the pre-treatment mean MP (P < 0.05). However, the mean perceived CA in the treatment groups was similar at pre- and post-treatment (P > 0.05). In a subgroup analysis of subjects in the treatment group, subjects with lower pre-treatment CA showed a significant CA increase after treatment (P = 0.004), but those with higher pre-treatment CA showed a significant decrease in CA (P = 0.001). These results suggest that prosthetic restoration for SDAs may benefit objective masticatory performance in patients needing replacement of missing posterior teeth, but the benefit in subjective chewing ability seems to be limited in subjects with perceived impairment in chewing ability before treatment. PMID- 26854878 TI - 3D-Printed Microfluidics. AB - The advent of soft lithography allowed for an unprecedented expansion in the field of microfluidics. However, the vast majority of PDMS microfluidic devices are still made with extensive manual labor, are tethered to bulky control systems, and have cumbersome user interfaces, which all render commercialization difficult. On the other hand, 3D printing has begun to embrace the range of sizes and materials that appeal to the developers of microfluidic devices. Prior to fabrication, a design is digitally built as a detailed 3D CAD file. The design can be assembled in modules by remotely collaborating teams, and its mechanical and fluidic behavior can be simulated using finite-element modeling. As structures are created by adding materials without the need for etching or dissolution, processing is environmentally friendly and economically efficient. We predict that in the next few years, 3D printing will replace most PDMS and plastic molding techniques in academia. PMID- 26854879 TI - MR neurographic orthopantomogram: Ultrashort echo-time imaging of mandibular bone and teeth complemented with high-resolution morphological and functional MR neurography. AB - PURPOSE: Panoramical radiographs or cone-beam computed tomography (CT) are the standard-of-care in dental imaging to assess teeth, mandible, and mandibular canal pathologies, but do not allow assessment of the inferior alveolar nerve itself nor of its branches. We propose a new technique for "MR neurographic orthopantomograms" exploiting ultrashort echo-time (UTE) imaging of bone and teeth complemented with high-resolution morphological and functional MR neurography. MATERIALS AND METHODS: The Institutional Review Board approved the study in 10 healthy volunteers. Imaging of the subjects mandibles at 3.0T (Magnetom Skyra, Siemens-Healthcare) using a 64-channel head coil with isotropic spatial resolution for subsequent multiplanar reformatting, was performed. Bone images were acquired using a 3D PETRA sequence (TE, 0.07 msec). Morphological nerve imaging was performed using a dedicated 3D PSIF and 3D SPACE STIR sequence. Functional MR neurography was accomplished using a new accelerated diffusion tensor-imaging (DTI) prototype sequence (2D SMS-accelerated RESOLVE). Qualitative and quantitative image analysis was performed and descriptive statistics are provided. RESULTS: Image acquisition and subsequent postprocessing into the MR neurographic orthopantomogram by overlay of morphological and functional images were feasible in all 10 volunteers without artifacts. All mandibular bones and mandibular nerves were assessable and considered normal. Fiber tractography with quantitative evaluation of physiological diffusion properties of mandibular nerves yielded the following mean +/- SD values: fractional anisotropy, 0.43 +/- 0.07; mean diffusivity (mm(2) /s), 0.0014 +/- 0.0002; axial diffusivity, 0.0020 +/- 0.0002, and radial diffusivity, 0.0011 +/- 0.0001. CONCLUSION: The proposed technique of MR neurographic orthopantomogram exploiting UTE imaging complemented with high-resolution morphological and functional MR neurography was feasible and allowed comprehensive assessment of osseous texture and neural microarchitecture in a single examination. J. Magn. Reson. Imaging 2016;44:393-400. PMID- 26854880 TI - Spin-Dependent Emission from Arrays of Planar Chiral Nanoantennas Due to Lattice and Localized Plasmon Resonances. AB - Chiral plasmonic nanoantennas manifest a strong asymmetric response to circularly polarized light. Particularly, the geometric handedness of a plasmonic structure can alter the circular polarization state of light emitted from nearby sources, leading to a spin-dependent emission direction. In past experiments, these effects have been attributed entirely to the localized plasmonic resonances of single antennas. In this work, we demonstrate that, when chiral nanoparticles are arranged in diffractive arrays, lattice resonances play a primary role in determining the spin-dependent emission of light. We fabricate 2D diffractive arrays of planar chiral metallic nanoparticles embedded in a light-emitting dye doped slab. By measuring the polarized photoluminescence enhancement, we show that the geometric chirality of the array's unit cell induces a preferential circular polarization, and that both the localized surface plasmon resonance and the delocalized hybrid plasmonic-photonic mode contribute to this phenomenon. By further mapping the angle-resolved degree of circular polarization, we demonstrate that strong chiral dissymmetries are mainly localized at the narrow emission directions of the surface lattice resonances. We validate these results against a coupled dipole model calculation, which correctly reproduces the main features. Our findings demonstrate that, in diffractive arrays, lattice resonances play a primary role into the light spin-orbit effect, introducing a highly nontrivial behavior in the angular spectra. PMID- 26854881 TI - Coagulopathy and its management in patients with severe burns. AB - Severe burn injury is associated with systemic coagulopathy. The changes in coagulation described in patients with severe burns resemble those found patients with sepsis or major trauma. Coagulopathy in patients with severe burns is characterized by procoagulant changes, and impaired fibrinolytic and natural anticoagulation systems. Both the timing of onset and the severity of hemostatic derangements are related to the severity of the burn. The exact pathophysiology and time course of coagulopathy are uncertain, but, at least in part, result from hemodilution and hypothermia. As the occurrence of coagulopathy in patients with severe burns is associated with increased comorbidity and mortality, coagulopathy could be seen as a potential therapeutic target. Clear guidelines for the treatment of coagulopathy in patients with severe burns are lacking, but supportive measures and targeted treatments have been proposed. Supportive measures are aimed at avoiding preventable triggers such as tissue hypoperfusion caused by shock, or hemodilution and hypothermia following the usually aggressive fluid resuscitation in these patients. Suggested targeted treatments that could benefit patients with severe burns include systemic treatment with anticoagulants, but sufficient randomized controlled trial evidence is lacking. PMID- 26854882 TI - Evaluation of the safety and efficacy of carbon ion radiotherapy for locally advanced adenoid cystic carcinoma of the tongue base. AB - BACKGROUND: Most cases of adenoid cystic carcinoma (ACC) of the tongue base are radioresistant, and are diagnosed in the advanced stage. Therefore, we evaluated the safety and efficacy of carbon ion radiotherapy (C-ion RT) for locally advanced ACC of the tongue base. METHODS: Eighteen patients with ACC of the tongue base were treated with C-ion RT between May 2002 and April 2014. Seventeen patients had T4a disease and 1 patient had T2 disease before C-ion RT. RESULTS: The median follow-up period was 57 months (range, 10-132 months). The 5-year local control rate was 92%. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 72% and 44%, respectively. Regarding late reactions, 2 patients developed grade 3 mandible osteoradionecrosis, and 1 had grade 3 hemorrhage of the tongue base. CONCLUSION: C-ion RT was effective with acceptable toxicities for locally advanced ACC of the tongue base. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2122-E2126, 2016. PMID- 26854883 TI - The differential diagnosis for failure to wean from mechanical ventilation. AB - PURPOSE OF REVIEW: In this review, we discuss the causes for a failed weaning trial and specific diagnostic tests that could be conducted to identify the cause for weaning failure. We briefly highlight treatment strategies that may enhance the chance of weaning success. RECENT FINDINGS: Impaired respiratory mechanics, respiratory muscle dysfunction, cardiac dysfunction, cognitive dysfunction, and metabolic disorders are recognized causes for weaning failure. In addition, iatrogenic factors may be at play. Most studies have focused on respiratory muscle dysfunction and cardiac dysfunction. Recent studies demonstrate that both ultrasound and electromyography are valuable tools to evaluate respiratory muscle function in ventilated patients. Sophisticated ultrasound techniques and biomarkers such as B-type natriuretic peptide, are valuable tools to identify cardiac dysfunction as a cause for weaning failure. Once a cause for weaning failure has been identified specific treatment should be instituted. Concerning treatment, both strength training and endurance training should be considered for patients with respiratory muscle weakness. Inotropes and vasodilators should be considered in case of heart failure. SUMMARY: Understanding the complex pathophysiology of weaning failure in combination with a systematic diagnostic approach allows identification of the primary cause of weaning failure. This will help the clinician to choose a specific treatment strategy and therefore may fasten liberation from mechanical ventilation. PMID- 26854884 TI - Chitosan nanoparticles reduce LPS-induced inflammatory reaction via inhibition of NF-kappaB pathway in Caco-2 cells. AB - Chitosan nanoparticles (CNP), an extensively oral-administered drug carrier, was investigated for the anti-inflammatory effects on LPS-inflamed Caco-2 cells and the relate mechanisms. CNP could alleviate the decrease of transepithelial electrical resistance (TEER) induced by LPS in Caco-2 monolayer, and significantly inhibit LPS-induced production of TNF-alpha, MIF, IL-8 and MCP-1 in a dose-dependent manner. PCR array assay revealed that CNP down-regulated the mRNA expression levels of TLR4 in LPS-inflamed Caco-2 cells. CNP was further showed to reduce cytoplasmic IkappaB-alpha degradation and nuclear NF-kappaB p65 levels in LPS-inflamed Caco-2 cells. These results suggested that CNP suppressed LPS-induced inflammatory response by decreasing permeability of intestinal epithelial monolayer and secretion of pro-inflammatory cytokine in Caco-2 cells, which were partially mediated by NF-kappaB signaling pathway. PMID- 26854885 TI - The immunomodulatory activities of pullulan and its derivatives in human pDC-like CAL-1 cell line. AB - In this study, acidic and alkaline pullulan derivates were synthesized and their immunomodulatory activities compared to pullulan were investigated in human pDC like CAL-1 cell line. Pullulan was reacted respectively with succinic anhydride and N-(-2-aminoethyl)-1,3-propanediamine/N,N-carbonyl diimidazole to form acidic pullulan monosuccinate (SUPL) and alkaline pullulan-g-N-(-2-aminoethyl)-1,3 propanediamine (AMPL). In CAL-1 cells, pullulan, SUPL and AMPL up-regulated the mRNA expressions of type I interferons (IFN), including IFN-alpha and IFN-beta1, and some other proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-23 (IL-23), and also significantly enhanced the protein expressions of IFN-alpha and TNF-alpha. The activation of nuclear factor kappa B (NF-kappaB) and the nuclear translocations of interferon regulation factors (IRFs), including IRF-3 and IRF-5, exhibited pivotal roles in the immune responses induced by pullulan, SUPL and AMPL. By comparison, pullulan and SUPL displayed weak effects on the activation of CAL-1 cells, but AMPL showed remarkably enhanced immunomodulatory activities, which were comparable to that induced by R848, an agonist for Toll-like receptor (TLR) 7/8. Our results suggested that AMPL, as an alkaline pullulan derivative, could be used as a potent immunomodulatory agent in the food and pharmacological fields. PMID- 26854886 TI - Biochemical characterization and functional analysis of the POU transcription factor POU-M2 of Bombyx mori. AB - POU-M2 is a homeodomain transcription factor which plays important roles in the development and silk synthesis of Bombyx mori. In this study, we expressed, purified and characterized POU-M2 and studied its transcription regulation on fibroin heavy chain gene of Bombyx mori. Gel filtration showed POU-M2 existed as a dimer in solution. Far-UV circular dichroism spectra indicated POU-M2 had a well-defined alpha-helix structure and the alpha-helix content was about 26.4%. The thermal unfolding transition of POU-M2 was a cooperative process. Tm, DeltaH and DeltaS were 45.15 +/- 0.2 degrees C, 138.4 +/- 0.5 KJ/mol and 0.4349 +/- 0.04 KJ/(mol.K), respectively. Western blotting analysis indicated the expression level of POU-M2 increased slightly from day 3 to day 7 of the fifth instar larvae in the posterior silk gland. POU-M2 was positioned in the nucleus of cells. The luciferase reporter assay demonstrated POU-M2 could stimulate the promoter activity of fibroin heavy chain gene, and the activation effect was dependent on the amount of POU-M2. Our study suggested POU-M2 may be involved in the transcriptional regulation of fibroin heavy chain gene. These findings expand toward a better understanding of the structure of POU-M2 and its function in silk synthesis of Bombyx mori. PMID- 26854887 TI - Characteristic features and dye degrading capability of agar-agar gel immobilized manganese peroxidase. AB - Immobilization of enzymes has been regarded as an efficient approach to develop biocatalyst with improved activity and stability characteristics under reaction conditions. In the present study, purified manganese peroxidase (MnP) from Ganoderma lucidum IBL-05 was immobilized in agar-agar support using entrapment technique. Maximum immobilization yield was accomplished at 4.0% agar-agar gel. The immobilized MnP exhibited better resistance to changes in pH and temperature than the free enzyme, with optimal conditions being pH 6.0 and 50 degrees C. The kinetic parameters Km and Kcat/Km for free and entrapped MnP were calculated to be 65.6 mM and 6.99 M(-1) s(-1), and 82 mM and 8.15 M(-1) s(-1), respectively. Thermo-stability was significantly improved after immobilization. After 120 h, the insolubilized MnP retained its activity up to 71.9% and 60.3% at 30 degrees C and 40 degrees C, respectively. It showed activity until 10th cycle and retained 74.3% residual activity after 3th cycle. The effects of H2O2, ionic strength and potential inhibitors on activity of free and immobilized enzyme were investigated. Moreover, the decolorization of three structurally different dyes was monitored in order to assess the degrading capability of the entrapped MnP. The decolorization efficiencies for all the tested dyes were 78.6-84.7% after 12h. The studies concluded that the toxicity of dyes aqueous solutions was significantly reduced after treatment. The remarkable catalytic, thermo-stability and re-cycling features of the agar-agar immobilized MnP display a high potential for biotechnological applications. PMID- 26854889 TI - When positive studies of novel therapies are subsequently nullified: cumulative meta-analyses in preeclampsia. AB - PURPOSE: The purpose of this study was to examine changes over time in the pooled effect size of randomized, double-blinded, placebo-controlled trials (RCTs) published on the protective effects of antioxidants and low dose aspirin against preeclampsia, and to identify determinants that may affect such changes. METHODS: Two recently published meta-analyses of RCTs examining the effects of antioxidant treatment or low dose aspirin on the rates of preeclampsia and its adverse effects were used. Chronological, cumulative meta-analyses were conducted to investigate the possibility of a time-dependent effect. The journal's impact factor, citation numbers of each paper, and their sample size, were correlated with the risk ratio (RR) of the study. RESULTS: The median sample size of positive antioxidant trials (i.e., showing protective effect) was tenfold smaller (median 267) than that of the negative trials (median 2120) (P = 0.017). A similar trend was seen for low dose aspirin studies. There was a significant correlation between study size and RR for the effects of antioxidants and low dose aspirin on intrauterine growth restriction (IUGR). There was no correlation between RR and citation number, or between RR and the journal's impact factor for the two therapeutic modalities. For both modalities, the journal's impact factor correlated significantly with the number of citations per year. Cumulative meta analyses revealed that during the first few years and studies, there was a seeming significant protective effect of antioxidant or aspirin against preeclampsia. For both treatment, the initial protective effects gradually disappeared and nullified by larger, later studies. CONCLUSIONS: Initial studies, often published in high impact factor journals, are cited significantly more times but do not exhibit a higher likelihood of predicting a correct long term answer. Studies with smaller sample sizes are more likely to be biased against the null hypothesis. As such, cumulative meta-analysis is an effective tool in predicting potential bias against the null hypothesis and the need for additional studies. PMID- 26854890 TI - Near infrared spectroscopy (NIRS) derived tissue oxygenation in critical illness. AB - PURPOSE: Near infrared spectroscopy (NIRS) is an emerging technology that can measure tissue oxygen saturation levels (StO2) and has many potential clinical applications. NIRS devices have been studied in various disease states in the pediatric as well as adult populations. A review of this technology, with its potential applications and a review of current evidence is presented. PRINCIPAL FINDINGS: NIRS-derived regional tissue oxygen saturation (StO2) is superior to pulse oximetry as it measures tissue oxygen saturation and reflects imbalance between oxygen supply and local demand. Becoming more widely available, it still does not have a firmly established role due to its technical limitations and to the lack of large multi-centric randomized controlled studies necessary to confirm its utility, cost-benefit effectiveness and role in improving patient outcomes. CONCLUSION: Widespread availability, ease of use, non-invasive nature and continuous data display makes it an attractive option for bedside clinical monitoring. PMID- 26854888 TI - Directed selection of influenza virus produces antigenic variants that match circulating human virus isolates and escape from vaccine-mediated immune protection. AB - Influenza vaccination does not provide 100% protection from infection, partly due to antigenic drift of the haemagglutinin (HA) protein. Low serum antibody titres increase the risk of infection. To determine whether there were additional correlates of risk, we examined the relationship between human serum immunity and antigenic variation in seasonal H3N2 influenza viruses. Seasonal H3N2 vaccine strains grown in the presence of heterogeneous human or mono-specific ferret antisera selected variants with mutations in the HA antigenic sites. Surprisingly, circulating strains infecting human subjects in the same seasons displayed mutations in the same positions, although only in one case did the change correspond to the same amino acid. Serum antibody titres were lower against both the in vitro selected and clinical isolates compared with the vaccine strains, suggesting that the mutations are relevant to vaccine failure. Antibody titres were also significantly lower in sera from infected subjects than in non-infected subjects, suggesting relatively poor responses to vaccination in the infected subjects. Collectively, the data suggest that risk from influenza infection is a result of poor response to vaccination, as well as encounter with drifted seasonal influenza virus antigenic variants. The results also show that directed selection under human immune pressure could reveal antigenic variants relevant to real-world drifted viruses, helping in annual vaccine re-formulation. PMID- 26854891 TI - Does stent strut design impact clinical outcomes: comparative safety and efficacy of Endeavor Resolute versus Resolute Integrity zotarolimus-eluting stents. AB - Percutaneous coronary intervention is the most commonly performed method of revascularizing obstructive coronary artery disease. The impact of stent strut design on clinical outcomes remains unclear. The Endeavour Resolute (ER-ZES) and the Resolute Integrity (RI-ZES) zotarolimus-eluting stents utilize identical polymers and anti-proliferative agents, differing only in their respective strut design. This study assessed the comparative safety and efficacy of these two stents in unrestricted contemporary real-world practice. METHODS: A total of 542 patients were identified, corresponding to 340 ER-ZES and 480 RI-ZES. The primary endpoint was major adverse cardiac events (MACE) defined by a composite of death, nonfatal myocardial infarction and stroke. Secondary endpoints included post procedural length of stay, in-stent restenosis, target lesion revascularization, target vessel revascularization, coronary artery bypass grafting and stent thrombosis. RESULTS: MACE occurred in 3.2% of the ER-ZES cohort and 5.0% of the RI-ZES cohort (p= 0.43). Adjusted analysis utilizing propensity score-adjusted odds ratio for MACE, was 1.37 (95% CI 0.46-4.07, p=0.57). The mortality rate (0.9% ER-ZES vs. 1.9% RI-ZES, p=0.59), non-fatal MI (2.3% ER-ZES vs. 3.1% RI-ZES, p=0.75) and stroke (0.0% ER-ZES vs. 0.3% RI-ZES, p=0.85) were not different. Additionally, there was no difference in any of secondary outcomes. CONCLUSIONS: The clinical performance and safety of both ER-ZES and RI-ZES were not statistically different, despite differences in stent strut design. PMID- 26854893 TI - Causes and outcome predictors of traumatic brain injury among emergency admitted pediatric patients at Cairo University Hospitals. AB - BACKGROUND: Traumatic brain injury (TBI) is a major global public health problem with significant morbidity and mortality, especially among the pediatric age group. Researchers are eager to find new diagnostic tools that might be useful for outcome prediction of pediatric TBI. OBJECTIVE: This study aims to determine the causes of TBI in pediatric patients admitted to the Emergency Hospital at Cairo University, and monitor and evaluate some clinical and laboratory markers for outcome prediction. PATIENTS AND METHODS: A hospital-based prospective study was carried out; all pediatric patients with TBI admitted to the New Emergency Hospital during 6 months (November 2014-April 2015) were enrolled in the study. A total of 67 pediatric patients with TBI were examined and investigated upon admission and followed prospectively till discharge or death. Probing questions were used to collect data on child abuse and neglect. The Glasgow Coma Scale (GCS) was used for clinical assessment, followed by cerebral tomography (computed tomography scan). Routine laboratory investigations, arterial blood gases (pH, PCO2, and HCO3), and coagulopathy tests (prothrombin time, prothrombin concentration, international normalized ratio, and D-dimer) were performed on days 1 and 7. RESULTS: Fall from height, traffic accidents, and direct head trauma represented 38.8, 34.3, and 21% of head trauma etiologies, respectively. Child neglect and abuse was detected in 62.7 and 18% of patients, respectively. Values of GCS at days 1 and 7 were significantly higher among survivors (P<0.001). D-dimer levels on days 1 and 7 were significantly higher among nonsurvivors (P<0.001). Receiver operating characteristics curve analysis showed the discriminative ability of D-dimer level on day 1 in predicting mortality with 89.3% sensitivity and 76.9% specificity. CONCLUSION AND RECOMMENDATIONS: Falls, traffic accidents, and direct head trauma were the most frequent etiologies for TBI in emergency admitted pediatric patients. Child neglect and abuse were the most prominent predisposing factors. GCS and D-dimer were the most important clinical and laboratory markers predicting mortality. Further large-scale studies are needed to determine the prevalence of TBIs and to prove the prognostic role of the D-dimer. PMID- 26854892 TI - Legacy effects of grassland management on soil carbon to depth. AB - The importance of managing land to optimize carbon sequestration for climate change mitigation is widely recognized, with grasslands being identified as having the potential to sequester additional carbon. However, most soil carbon inventories only consider surface soils, and most large-scale surveys group ecosystems into broad habitats without considering management intensity. Consequently, little is known about the quantity of deep soil carbon and its sensitivity to management. From a nationwide survey of grassland soils to 1 m depth, we show that carbon in grassland soils is vulnerable to management and that these management effects can be detected to considerable depth down the soil profile, albeit at decreasing significance with depth. Carbon concentrations in soil decreased as management intensity increased, but greatest soil carbon stocks (accounting for bulk density differences), were at intermediate levels of management. Our study also highlights the considerable amounts of carbon in subsurface soil below 30 cm, which is missed by standard carbon inventories. We estimate grassland soil carbon in Great Britain to be 2097 Tg C to a depth of 1 m, with ~60% of this carbon being below 30 cm. Total stocks of soil carbon (t ha( 1) ) to 1 m depth were 10.7% greater at intermediate relative to intensive management, which equates to 10.1 t ha(-1) in surface soils (0-30 cm), and 13.7 t ha(-1) in soils from 30 to 100 cm depth. Our findings highlight the existence of substantial carbon stocks at depth in grassland soils that are sensitive to management. This is of high relevance globally, given the extent of land cover and large stocks of carbon held in temperate managed grasslands. Our findings have implications for the future management of grasslands for carbon storage and climate mitigation, and for global carbon models which do not currently account for changes in soil carbon to depth with management. PMID- 26854894 TI - Prevalence of supernumerary teeth in a nonsyndromic Syrian sample. AB - BACKGROUND: Supernumerary teeth (ST), also known as hyperdontia, is a condition in which more than the normal number of teeth are present in the series. The prevalence of ST varies between and within different populations. These teeth may cause various complications. The aim of the current study was to investigate the prevalence and characteristics of ST in Damascus inhabitants, Syria. MATERIALS AND METHODS: A cross-sectional study was carried out using retrospectively collected digital panoramic radiographs of 2753 patients (1047 males and 1706 females) ranging in age from 12.2 to 20.5 years between January 2012 and December 2014. These radiographs were obtained from private dental offices spread across Damascus, Syria. For each patient with ST, the demographic variables, number, location, type, position, morphology of ST, and complications were recorded. RESULTS: ST were detected in 39 patients (1.4%), of whom 25 (64.1%) were males and 14 (35.9%) were females, with a male to female ratio of 1.8 : 1 (P<0.001). Mesiodens was the most prevalent ST (39.1%), followed by supernumerary premolars (28.3%), supernumerary laterals (26.1%), distomolars (4.3%), and paramolars (2.2%). This series includes cases with one and two ST. Of the 46 ST detected, 56.5% had a conical morphology, 89.1% were in a vertical position, and 19.6% were erupted. ST caused displacement of the adjacent teeth in 17 cases (37.0%) and the impaction of the permanent teeth in five cases (10.9%). CONCLUSION AND RECOMMENDATIONS: The prevalence of ST in Damascus inhabitants was found to be 1.4%; the most frequent type was mesiodens. A conical morphology was found to be the most common form of ST. Displacement of permanent teeth is the most frequent complication. Further studies should be carried out on more representative samples of both the public and the private sector patients. PMID- 26854896 TI - Prevalence of HIV among blood donors at Beni-Suef University Hospital Blood Bank, Egypt. AB - BACKGROUND: The prevalence rate of HIV among blood donors differs between countries and regions. The aim of this study was to determine the prevalence of HIV among blood donors in the Blood Bank of Beni-Suef University Hospital, Egypt, during the 5 years 2010-2014. MATERIALS AND METHODS: This is a retrospective, record-based study that involved the abstraction of data of all donors from registers at the Beni-Suef University Hospital Blood Bank during the period 2010 2014. Data were transformed onto data sheets and entered into a computer database. RESULTS: Of the 26 442 blood donors, 24 733 (93.5%) were male and 1709 (6.5%) were female. The mean age for the whole group was 29.88+/-7.6 (range=18 65) years. The prevalence of HIV was 0.1% (14 donors); of them, there were 13 (92.9%) male donors and one (7.1%) female donor, but this difference was not statistically significant (P=0.9). More than 50% (57.1%) of HIV-positive patients (8/14) were between 20 and 29 years of age and four (28.6%) were between 30 and 39 years of age, with no statistically significant difference (P=0.08). There were HIV-HCV coinfections in two donors (14.3%) (P=0.5). The highest percentage (35.7%) of HIV-positive donors (five donors) were of blood group B, with no significant difference (P=0.2). CONCLUSION AND RECOMMENDATIONS: The prevalence of HIV was low (0.1%) among blood donors in Beni-Suef, Egypt, with no significant differences for age or sex. The incidence of HIV-HCV coinfection was 14.3%. We recommend strengthening of the healthcare system by improving the screening facilities for HIV and other transfusion-transmissible infections. PMID- 26854895 TI - Evaluation of validity of Integrated Management of Childhood Illness guidelines in identifying edema of nutritional causes among Egyptian children. AB - OBJECTIVE: The aim of this study was to assess the validity of the Integrated Management of Childhood Illness (IMCI) algorithm to detect edematous type of malnutrition in Egyptian infants and children ranging in age from 2 months to 5 years. MATERIALS AND METHODS: This study was carried out by surveying 23 082 children aged between 2 months and 5 years visiting the pediatric outpatient clinic, Ain Shams University Hospital, over a period of 6 months. Thirty-eight patients with edema of both feet on their primary visit were enrolled in the study. Every child was assessed using the IMCI algorithm 'assess and classify' by the same physician, together with a systematic clinical evaluation with all relevant investigations. RESULTS: Twenty-two patients (57.9%) were proven to have nutritional etiology. 'Weight for age' sign had a sensitivity of 95.5%, a specificity of 56%, and a diagnostic accuracy of 78.95% in the identification of nutritional edema among all cases of bipedal edema. Combinations of IMCI symptoms 'pallor, visible severe wasting, fever, diarrhea', and 'weight for age' increased the sensitivity to 100%, but with a low specificity of 38% and a diagnostic accuracy of 73.68%. CONCLUSION AND RECOMMENDATIONS: Bipedal edema and low weight for age as part of the IMCI algorithm can identify edema because of nutritional etiology with 100% sensitivity, but with 37% specificity. Revisions need to be made to the IMCI guidelines published in 2010 by the Egyptian Ministry of Health in the light of the new WHO guidelines of 2014. PMID- 26854897 TI - Isolation and molecular identification of Naegleria fowleri from Nile river, Egypt. AB - BACKGROUND: Members of the genus Naegleria are free-living amoebae distributed in various aquatic environments. Naegleria fowleri is the only species that can cause fatal primary amoebic meningoencephalitis in humans. MATERIALS AND METHODS: A total of 48 Nile water samples were collected from the water stream passing though Cairo. The samples were processed for the detection of Naegleria spp. using non-nutrient agar at 45 degrees C. The isolates of Naegleria spp. were identified based on the morphologic criteria of trophozoite, flagellated and cyst stages. Molecular characterization of the isolates was performed using PCR. RESULTS: The obtained results showed that Naegleria spp. were found in 45.8% of Nile water samples by means of microscopic examination. Seasonally, the highest prevalence of Naegleria spp. was recorded in summer (66.7%). Moreover, the highest prevalence of N. fowleri was recorded in summer (25%). CONCLUSION: The occurrence of heat-tolerant Naegleria spp., especially N. fowleri, in Nile water should be considered as a potential health threat. PMID- 26854898 TI - Association between quality of life, menopausal status, and sociodemographic factors among middle-aged women in Iran. AB - OBJECTIVE: Assessment of overall health, well-being, and quality of life (QoL) during middle age and menopause deserves special attention. The aim of this study was to investigate the effect of menopausal status and some sociodemographic variables on QoL among middle-aged women in Semnan, Iran. PARTICIPANTS AND METHODS: This cross-sectional survey was conducted in 2012 in Semnan, Iran. The participants included 770 women aged 45-60 years. The data were collected by interview using a structured questionnaire that included sociodemographic characteristics, data on menopausal status, and QoL measurement using the Menopause-Specific Quality of Life questionnaire. RESULTS: The mean+/-SD age of the women was 50.9+/-4.7 years. The overall unadjusted mean scores obtained for each domain were as follows: vasomotor: 1.83+/-1.86; psychosocial: 1.62+/-1.41; physical: 1.98+/-1.28; and sexual: 1.63+/-1.87. Logistic regression analysis showed that menopausal status was significantly associated with QoL in all domains, except the psychosocial domain. Age, BMI, household income, and number of children were significantly associated with impairment in QoL. Marital status, educational level, and residential area did not show any association with QoL in multivariate analysis. CONCLUSION AND RECOMMENDATIONS: Our findings confirm previous literature on the negative impact of menopausal symptoms on QoL, and show the interaction of some sociodemographic characteristics including age, number of children, household income, and BMI, on QoL. Health professionals should ensure that they consider a range of factors in middle-aged women's lives and provide insight into possible treatment strategies and lifestyle interventions for improving QoL. PMID- 26854899 TI - Knowledge, attitude, and practice of osteoporosis among Saudis: a community-based study. AB - BACKGROUND: Osteoporosis is a global public health problem currently affecting millions of people worldwide, and Saudi Arabia is not an exception. Awareness and perceptions of susceptibility and belief in the seriousness of a disease can help in its prevention and control. We aimed to assess knowledge, attitude, and practices for osteoporosis among Saudi general population and to identify its determining factors. METHODS: A cross-sectional survey of people aged 18 years or older representing every region in the Kingdom of Saudi Arabia was carried out. A total of 2174 self-administered questionnaires were distributed to identify the levels of knowledge, attitude, and practice. RESULTS: Responses were obtained from 1830 individuals (42% female and 58% male). The majority of the study sample had heard about osteoporosis (78%). There were significant associations between the level of awareness and the following sociodemographics of the participants: age, sex, education, occupation, income, and residence (P<0.01). Regular practice of the main preventive behaviors was correlated with an increase in the level of awareness. CONCLUSION AND RECOMMENDATIONS: The majority of the study cohort had heard about osteoporosis. Female respondents were more knowledgeable. Age was negatively correlated with the level of awareness. Awareness levels and the main sociodemographic determinants were significantly associated. The study recommended that health authorities and physicians should have better involvement in patient education efforts to improve and maintain the information provided on osteoporosis. PMID- 26854900 TI - Bio-orthogonal Coupling as a Means of Quantifying the Ligand Density on Hydrophilic Quantum Dots. AB - We describe the synthesis of two metal-coordinating ligands that present one or two lipoic acid (LA) anchors, a hydrophilic polyethylene glycol (PEG) segment and a terminal reactive group made of an azide or an aldehyde, two functionalities with great utility in bio-orthogonal coupling techniques. These ligands were introduced onto the QD surfaces using a combination of photochemical ligation and mixed cap exchange strategy, where control over the fraction of azide and aldehyde groups per nanocrystal can be easily achieved: LA-PEG-CHO, LA-PEG-N3, and bis(LA)-PEG-CHO. We then demonstrate the application of two novel bio orthogonal coupling strategies directly on luminescent quantum dot (QD) surfaces that use click chemistry and hydrazone ligation under catalyst-free conditions. We applied the highly efficient hydrazone ligation to couple 2-hydrozinopyridine (2-HP) to aldehyde-functionalized QDs, which produces a stable hydrazone chromophore with a well-defined optical signature. This unique optical feature has enabled us to extract a measure for the ligand density on the QDs for a few distinct sizes and for different ligand architectures, namely mono-LA-PEG and bis(LA)-PEG. We found that the foot-print-area per ligand was unaffected by the nanocrystal size but strongly depended on the ligand coordination number. Additionally, we showed that when the two bio-orthogonal functionalities (aldehyde and azide) are combined on the same QD platform, the nanocrystal can be specifically reacted with two distinct targets and with great specificity. This design yields QD platforms with distinct chemoselectivities that are greatly promising for use as carriers for in vivo imaging and delivery. PMID- 26854901 TI - Augmenting Ion Trap Mass Spectrometers Using a Frequency Modulated Drift Tube Ion Mobility Spectrometer. AB - Historically, high pressure ion mobility drift tubes have suffered from low ion duty cycles and this problem is magnified when such instrumentation is coupled with ion trap mass spectrometers. To significantly alleviate these issues, we outline the result from coupling an atmospheric pressure, dual-gate drift tube ion mobility spectrometer (IMS) to a linear ion trap mass spectrometer (LIT-MS) via modulation of the ion beam with a linear frequency chirp. The time-domain ion current, once Fourier transformed, reveals a standard ion mobility drift spectrum that corresponds to the standard mode of mobility analysis. By multiplexing the ion beam, it is possible to successfully obtain drift time spectra for an assortment of simple peptide and protein mixtures using an LIT-MS while showing improved signal intensity versus the more common signal averaging technique. Explored here are the effects of maximum injection time, solution concentration, total experiment time, and frequency swept on signal-to-noise ratios (SNRs) and resolving power. Increased inject time, concentration, and experiment time all generally led to an improvement in SNR, while a greater frequency swept increases the resolving power at the expense of SNR. Overall, chirp multiplexing of a dual gate IMS system coupled to an LIT-MS improves ion transmission, lowers analyte detection limits, and improves spectral quality. PMID- 26854902 TI - Modulatory effect of romantic love on value estimation and its neural mechanism. AB - Any decision that is based upon personal preferences utilizes subjective values; however, for objectively equivalent items, whether romantic love modulates subjective value as well as the neural mechanism of this process remains unknown. In this functional MRI study, 30 items with equivalent value were first selected and assigned into three groups, and participants were trained to associate each group of items with their lover, a familiar person, or an unfamiliar person. Thereafter, the participant rated the values of the items during functional MRI scanning, after which they performed a post-test of memory of the associations. Behavioral results demonstrated that, although the items were well remembered, the items that were associated with the lover were rated significantly higher than the other images. Furthermore, we found higher activation related to the items associated with the lover than for those associated with a familiar person or an unfamiliar person in the striatum and the medial prefrontal cortex (related to cognitive control process). Finally, a morphometric analysis demonstrated that gray matter thickness in the striatum was positively associated with gray matter thickness in the medial prefrontal cortex but negatively correlated with the activation that was elicited by the items that were associated with the lover in the same brain area. Our results suggest that the romantic love-related brain region (the striatum) may modulate subjective value through the striatal prefrontal pathway, further suggesting a potential bottom-up (control impulsivity) process. PMID- 26854904 TI - Conditioned taste aversion prevents the long-lasting BDNF-induced enhancement of synaptic transmission in the insular cortex: A metaplastic effect. AB - Homeostatic plasticity mechanisms dynamically adjust synaptic strengths to promote stability that is crucial for memory storage. Metaplasticity is an example of these forms of plasticity that modify the capacity of synapses to experience subsequent Hebbian modifications. In particular, training in several behavioral tasks modifies the ability to induce long-term potentiation (LTP). Recently, we have reported that prior training in conditioned taste aversion (CTA) prevents the subsequent induction of LTP generated by high frequency stimulation in the projection from the basolateral nucleus of the amygdala (Bla) to the insular cortex (IC). One of the key molecular players that underlie long term synaptic plasticity is brain-derived neurotrophic factor (BDNF). Previous studies from our group reported that acute microinfusion of BDNF in the IC induces a lasting potentiation of synaptic efficacy at the Bla-IC projection. Thus, the aim of the present study was to analyze whether CTA training modifies the ability to induce subsequent BDNF-induced potentiation of synaptic transmission in the Bla-IC projection in vivo. Accordingly, CTA trained rats received intracortical microinfusion of BDNF in order to induce lasting potentiation 48h after the aversion test. Our results show that CTA training prevents the induction of in vivo BDNF-LTP in the Bla-IC projection. The present results provide evidence that CTA modulates BDNF-dependent changes in IC synaptic strength. PMID- 26854903 TI - Distinct medial temporal networks encode surprise during motivation by reward versus punishment. AB - Adaptive motivated behavior requires predictive internal representations of the environment, and surprising events are indications for encoding new representations of the environment. The medial temporal lobe memory system, including the hippocampus and surrounding cortex, encodes surprising events and is influenced by motivational state. Because behavior reflects the goals of an individual, we investigated whether motivational valence (i.e., pursuing rewards versus avoiding punishments) also impacts neural and mnemonic encoding of surprising events. During functional magnetic resonance imaging (fMRI), participants encountered perceptually unexpected events either during the pursuit of rewards or avoidance of punishments. Despite similar levels of motivation across groups, reward and punishment facilitated the processing of surprising events in different medial temporal lobe regions. Whereas during reward motivation, perceptual surprises enhanced activation in the hippocampus, during punishment motivation surprises instead enhanced activation in parahippocampal cortex. Further, we found that reward motivation facilitated hippocampal coupling with ventromedial PFC, whereas punishment motivation facilitated parahippocampal cortical coupling with orbitofrontal cortex. Behaviorally, post-scan testing revealed that reward, but not punishment, motivation resulted in greater memory selectivity for surprising events encountered during goal pursuit. Together these findings demonstrate that neuromodulatory systems engaged by anticipation of reward and punishment target separate components of the medial temporal lobe, modulating medial temporal lobe sensitivity and connectivity. Thus, reward and punishment motivation yield distinct neural contexts for learning, with distinct consequences for how surprises are incorporated into predictive mnemonic models of the environment. PMID- 26854905 TI - Expression of fibronectin binding protein A (FnBPA) from Staphylococcus aureus at the cell surface of Lactococcus lactis improves its immunomodulatory properties when used as protein delivery vector. AB - A recombinant strain of Lactococcus lactis displaying a cell-surface anchored fibronectin binding protein A (FnBPA) from Staphylococcus aureus (LL-FnBPA) had been shown to be more efficient in delivering plasmid than its wild-type counterpart both in vitro and in vivo, and have the ability to orientate the immune response toward a Th2 profile in a context of a DNA vaccination. The aim of this work was to test whether this LL-FnBPA strain could shape the immune response after mucosal administration in mice. For this, we used a mouse model of human papilloma virus (HPV)-induced cancer and a L. lactis strain displaying at its cell surface both HPV-16-E7 antigen (LL-E7) and FnBPA (LL-E7+FnBPA). Our results revealed a more efficient systemic Th1 immune response with recombinant LL-E7+FnBPA. Furthermore, mice vaccinated with LL-E7+FnBPA were better protected when challenged with HPV-16-induced tumors. Altogether, the results suggest that FnBPA displays adjuvant properties when used in the context of mucosal delivery using L. lactis as a live vector. PMID- 26854907 TI - HPV vaccination coverage of teen girls: the influence of health care providers. AB - BACKGROUND: Between 2010 and 2014, the percentage of 13-17 year-old girls administered >=3 doses of the human papilloma virus (HPV) vaccine ("fully vaccinated") increased by 7.7 percentage points to 39.7%, and the percentage not administered any doses of the HPV vaccine ("not immunized") decreased by 11.3 percentage points to 40.0%. OBJECTIVE: To evaluate the complex interactions between parents' vaccine-related beliefs, demographic factors, and HPV immunization status. METHODS: Vaccine-related parental beliefs and sociodemographic data collected by the 2010 National Immunization Survey-Teen among teen girls (n=8490) were analyzed. HPV vaccination status was determined from teens' health care provider (HCP) records. RESULTS: Among teen girls either unvaccinated or fully vaccinated against HPV, teen girls whose parent was positively influenced to vaccinate their teen daughter against HPV were 48.2 percentage points more likely to be fully vaccinated. Parents who reported being positively influenced to vaccinate against HPV were 28.9 percentage points more likely to report that their daughter's HCP talked about the HPV vaccine, 27.2 percentage points more likely to report that their daughter's HCP gave enough time to discuss the HPV shot, and 43.4 percentage points more likely to report that their daughter's HCP recommended the HPV vaccine (p<0.05). Among teen girls administered 1-2 doses of the HPV vaccine, 87.0% had missed opportunities for HPV vaccine administration. CONCLUSION: Results suggest that an important pathway to achieving higher >=3 dose HPV vaccine coverage is by increasing HPV vaccination series initiation though HCP talking to parents about the HPV vaccine, giving parents time to discuss the vaccine, and by making a strong recommendation for the HPV. Also, HPV vaccination series completion rates may be increased by eliminating missed opportunities to vaccinate against HPV and scheduling additional follow-up visits to administer missing HPV vaccine doses. PMID- 26854906 TI - A first-in-human phase 1 trial to evaluate the safety and immunogenicity of the candidate tuberculosis vaccine MVA85A-IMX313, administered to BCG-vaccinated adults. AB - INTRODUCTION: There is an urgent need for a new and effective tuberculosis vaccine because BCG does not sufficiently prevent pulmonary disease. IMX313 is a novel carrier protein designed to improve cellular and humoral immunity. MVA85A IMX313 is a novel vaccine candidate designed to boost immunity primed by bacillus Calmette-Guerin (BCG) that has been immunogenic in pre-clinical studies. This is the first evaluation of IMX313 delivered as MVA85A-IMX313 in humans. METHODS: In this phase 1, open-label first-in-human trial, 30 healthy previously BCG vaccinated adults were enrolled into three treatment groups and vaccinated with low dose MVA85A-IMX313 (group A), standard dose MVA85A-IMX313 (group B), or MVA85A (group C). Volunteers were followed up for 6 months for safety and immunogenicity assessment. RESULTS: The majority of adverse events were mild and there were no vaccine-related serious AEs. Both MVA85A-IMX313 and MVA85A induced a significant increase in IFN-gamma ELISpot responses. There were no significant differences between the Ag85A ELISpot and intracellular cytokine responses between the two study groups B (MVA85A-IMX313) and C (MVA85A) at any time point post-vaccination. CONCLUSION: MVA85A-IMX313 was well tolerated and immunogenic. There was no significant difference in the number of vaccine-related, local or systemic adverse reactions between MVA85A and MVA85A-IMX313 groups. The mycobacteria-specific cellular immune responses induced by MVA85A-IMX313 were not significantly different to those detected in the MVA85A group. In light of this encouraging safety data, further work to improve the potency of molecular adjuvants like IMX313 is merited. This trial was registered on clinicatrials.gov ref. NCT01879163. PMID- 26854908 TI - Should professionals caring for children be vaccinated? Community perspectives on health care and child care worker immunisation. AB - OBJECTIVE: Several immunisations including influenza and pertussis are specifically recommended for healthcare workers (HCW) and childcare workers (CCW). This study aimed to assess community attitudes to HCW and CCW immunisation recommendations for pertussis and seasonal influenza. METHODS: A cross-sectional study was conducted by Computer Assisted Telephone Interviewing (CATI) from April to May 2011. Statistical analyses used data weighted to the South Australian population by probability of selection, age, gender and geographical location using benchmarks derived from the 2009 Census population figures. RESULTS: Almost all respondents supported vaccination of HCWs and CCWs against pertussis and influenza. For pertussis, 95.3% agreed nurses, 94.9% agreed doctors and 94.7% agreed CCWs have an obligation to be vaccinated. For influenza, 91.4% agreed nurses, 90.7% agreed doctors and 89.9% agreed CCWs have an obligation to be vaccinated. We identified higher support for protection against pertussis compared to influenza for all three groups of workers (p<0.001). There were higher concerns if CCWs compared to HCWs were not vaccinated against pertussis (OR=2.78) and influenza (OR=1.99). Young (18-30 years) and older age (60+ years) and lower educational attainment were predictors of support for HCWs and CCWs to be vaccinated against influenza. For pertussis, lower educational attainment was a predictor of support for HCWs immunisation. CONCLUSIONS: Community support for CCW and HCW immunisation is strong with CCW immunisation was considered a priority. Pertussis immunisation was considered a higher priority than influenza immunisation for HCWs and CCWs. CCW immunisation should be considered for inclusion in public health immunisation programmes. PMID- 26854909 TI - Trends in reasons for non-receipt of influenza vaccination during pregnancy in Georgia, 2004-2011. AB - BACKGROUND: Considerable research has identified barriers to antenatal influenza vaccination, yet no research has explored temporal trends in reasons for non receipt. PURPOSE: To examine trends in reasons for non-receipt of influenza vaccination during pregnancy. METHODS: Serial cross-sectional analyses using 8 years of Georgia Pregnancy Risk Assessment Monitoring Survey (PRAMS) data were conducted. Weighted logistic regression was used to examine trends in the prevalence of citing reasons for non-receipt over time. RESULTS: Between 2004 and 2011, 8300 women reported no influenza vaccination during or immediately before pregnancy. Proportions of women citing "doctor didn't mention vaccination," "in first trimester during influenza season," and "not pregnant during influenza season" decreased significantly over time (Doctor didn't mention: 48.0% vs. 27.1%, test for trend p<0.001; in first trimester: 26.8% vs. 16.3%, test for trend p<0.001; not influenza season: 24.2% vs. 12.7%, test for trend p=0.001). Safety concerns increased over 2004 proportions in 2010 (concern about side effects for me: 40.2% vs. 28.5%, prevalence ratio (PR): 1.41, 95% confidence interval (CI): 1.16, 1.71; concern about harming my baby: 38.9% vs. 31.0%, PR=1.26, 95% CI: 1.04, 1.53) and 2011 (concern about side effects for me: 39.0% vs. 28.5%, PR=1.37, 95% CI: 1.13, 1.65; concern about harming my baby: 38.8% vs. 31.0%, PR=1.25, 95% CI: 1.04, 1.50). Following the 2009/2010 H1N1 pandemic, more Hispanic women cited concern about vaccination harming their baby than other women; in 2011, their concern remained elevated relative to non-Hispanic white women (63% vs. 35%; adjusted PR=1.79, 95% CI: 1.23, 2.61). CONCLUSION: Examining trends in reasons for non-receipt of antenatal influenza vaccination can reflect successes related to vaccine promotion and areas for improvement. By highlighting differential impacts of the 2009/2010 H1N1 pandemic, we reveal opportunities for additional research on tailoring vaccine promotion efforts to specific types of women. PMID- 26854910 TI - Knowledge, attitudes and beliefs related to seasonal influenza vaccine among pregnant women in Thailand. AB - BACKGROUND: In 2009, Thailand recommended pregnant women be prioritized for influenza vaccination. Vaccine uptake among Thai pregnant women is lower than other high-risk groups. METHODS: During December 2012-April 2013, we conducted a cross-sectional survey of a convenience sample of Thai pregnant women aged >= 15 years attending antenatal clinics at public hospitals in 8 of 77 provinces. A self-administered questionnaire covered knowledge, attitudes, and beliefs related to influenza vaccination using the Health Belief Model. We examined factors associated with willingness to be vaccinated using log-binomial regression models. RESULTS: The survey was completed by 1031 (96%) of 1072 pregnant women approached. A total of 627 (61%) women had heard about influenza vaccine and were included in the analysis, of whom 262 (42%) were willing to be vaccinated, 155 (25%) had received a healthcare provider recommendation for influenza vaccination and 25 (4%) had received the influenza vaccine during the current pregnancy. In unadjusted models, high levels of perceptions of susceptibility (prevalence ratio [PR] 1.5, 95% CI 1.2-2.0), high levels of belief in the benefits of vaccination (PR 2.3, 95% CI 1.7-3.1), moderate (PR 1.7, 95% CI 1.2-2.3) and high (PR 3.4, 95% CI 2.6-4.5) levels of encouragement by others to be vaccinated (i.e., cues to action) were positively associated with willingness to be vaccinated. Moderate (PR 0.5, 95% CI 0.4-0.7) and high levels of (PR 0.5, 95% CI 0.4-0.8) perceived barriers were negatively associated with willingness to be vaccinated. In the final adjusted model, only moderate (PR 1.5, 95% CI 1.1-2.0) and high levels of cues to action (PR 2.7, 95% CI 2.0-3.6) were statistically associated with willingness to be vaccinated. CONCLUSION: Cues to action were associated with willingness to be vaccinated and can be used to inform communication strategies during the vaccine campaign to increase influenza vaccination among Thai pregnant women. PMID- 26854911 TI - Effectiveness of subunit influenza vaccination in the 2014-2015 season and residual effect of split vaccination in previous seasons. AB - BACKGROUND: In Navarra, Spain, subunit vaccine was first used in the 2014-2015 season, whereas trivalent split-virion influenza vaccines had been used in previous seasons. We estimate the effectiveness of the subunit vaccine in the current season and split vaccine in the two previous seasons against laboratory confirmed influenza in the 2014-2015 season. METHODS: Patients with influenza like illness hospitalized or attended by sentinel general practitioners were swabbed for influenza testing. The previous and current vaccine status of laboratory-confirmed cases was compared to test-negative controls. RESULTS: Among 1213 patients tested, 619 (51%) were confirmed for influenza virus: 52% influenza A(H3N2), 46% influenza B, and 2% A(H1N1)pdm09. The overall effectiveness for subunit vaccination in the current season was 19% (95% confidence interval [CI]: 13 to 42), 2% (95%CI: -47 to 35) against influenza A(H3N2) and 32% (95%CI: -4 to 56) against influenza B. The effectiveness against any influenza was 67% (95%CI: 17-87) for 2012-2013 and 2013-2014 vaccination only, 42% (95%CI: -31 to 74) for 2014-2015 vaccination only, and 38% (95%CI: 8-58) for vaccination in the 2012 2013, 2013-2014 and 2014-2015 seasons. The same estimates against influenza A(H3N2) were 47% (95%CI: -60 to 82), -54% (95%CI: -274 to 37) and 28% (95%CI: -17 to 56), and against influenza B were 82% (95%CI: 19-96), 93% (95%CI: 45-99) and 43% (95%CI: 5-66), respectively. CONCLUSION: These results suggest a considerable residual protection of split vaccination in previous seasons, low overall effectiveness of current season subunit vaccination, and possible interference between current subunit and previous split vaccines. PMID- 26854912 TI - Corrigendum: Graphene based flexible electrochromic devices. PMID- 26854913 TI - U(v) in metal uranates: a combined experimental and theoretical study of MgUO4, CrUO4, and FeUO4. AB - Although pentavalent uranium can exist in aqueous solution, its presence in the solid state is uncommon. Metal monouranates, MgUO4, CrUO4 and FeUO4 were synthesized for detailed structural and energetic investigations. Structural characteristics of these uranates used powder X-ray diffraction, synchrotron X ray absorption spectroscopy, X-ray photoelectron spectroscopy, and (57)Fe Mossbauer spectroscopy. Enthalpies of formation were measured by high temperature oxide melt solution calorimetry. Density functional theory (DFT) calculations provided both structural and energetic information. The measured structural and thermodynamic properties show good consistency with those predicted from DFT. The presence of U(5+) has been solidly confirmed in CrUO4 and FeUO4, which are thermodynamically stable compounds, and the origin and stability of U(5+) in the system was elaborated by DFT. The structural and thermodynamic behaviour of U(5+) elucidated in this work is relevant to fundamental actinide redox chemistry and to applications in the nuclear industry and radioactive waste disposal. PMID- 26854914 TI - Bioinspired Artificial Melanosomes As Colorimetric Indicators of Oxygen Exposure. AB - Many industries require irreversibly responsive materials for use as sensors or detectors of environmental exposure. We describe the synthesis and fabrication of a nontoxic surface coating that reports oxygen exposure of the substrate material through irreversible formation of colored spots. The coating consists of a selectively permeable rubber film that contains the colorless organic precursors to darkly pigmented synthetic melanin. Melanin synthesis within the film is triggered by exposure to molecular oxygen. The selectively permeable rubber film regulates the rate of oxygen diffusion, enabling independent control of the sensitivity and response time of the artificial melanosome, while preventing leaching of melanin or its precursors. PMID- 26854915 TI - Improving Prenatal Care for Minority Women. AB - Since the inception of prenatal care in the early 1900s, the focus of care has been on risk reduction rather than on health promotion. Prenatal care began as individualized care, but more recently group prenatal care has been shown to be very successful in improving birth outcomes. For all women, an emphasis on improving health behaviors is important at this critical time while women are engaging regularly with the healthcare system. An emphasis on mental health promotion may decrease some of the disparities in birth outcomes that are well documented between minority and majority women, as minority women are known to experience increased levels of stress, anxiety, and depression. Providing support for pregnant women and incorporating knowledge and skills through prenatal care may promote both physical and mental health in minority women. PMID- 26854916 TI - Weighting sequence variants based on their annotation increases power of whole genome association studies. AB - The consensus approach to genome-wide association studies (GWAS) has been to assign equal prior probability of association to all sequence variants tested. However, some sequence variants, such as loss-of-function and missense variants, are more likely than others to affect protein function and are therefore more likely to be causative. Using data from whole-genome sequencing of 2,636 Icelanders and the association results for 96 quantitative and 123 binary phenotypes, we estimated the enrichment of association signals by sequence annotation. We propose a weighted Bonferroni adjustment that controls for the family-wise error rate (FWER), using as weights the enrichment of sequence annotations among association signals. We show that this weighted adjustment increases the power to detect association over the standard Bonferroni correction. We use the enrichment of associations by sequence annotation we have estimated in Iceland to derive significance thresholds for other populations with different numbers and combinations of sequence variants. PMID- 26854919 TI - A developmental toxicity study of 3S, 3'S-Astaxanthin in New Zealand white rabbits. AB - Astaxanthin, a naturally occurring pigment used to give the characteristic orange pink colour to salmonid fish reared in aquaculture, is also marketed as a dietary supplement. Synthetic 3S, 3'S-Astaxanthin was tested for potential harmful effects on the in utero development of New Zealand white rabbits in a study according to international regulatory guidelines. There were two control groups, one being a placebo administration and three dose levels corresponding to 100, 200, and 400 mg of 3S, 3'S-Astaxanthin per kg body weight/day. The group sizes varied from 23 to 27 litters, providing approximately 200 fetuses per group for evaluation of developmental toxicity. There were no significant effects on the health of the does, nor on the size and viability of the litters. Malformations, both external and internal, were rare and occurred in all groups, including controls with no indication of a treatment relationship. Variations were much more common, being found in all litters. However, when examined by type and frequency, no pattern emerged indicating a relationship to administration of the test substance. It is concluded that administration of 3S, 3'S-Astaxanthin in a gelatin/carbohydrate powder formulation throughout pregnancy up to 400 mg/kg body weight/day is without harmful effects on reproduction or fetal development. PMID- 26854917 TI - Integrative approaches for large-scale transcriptome-wide association studies. AB - Many genetic variants influence complex traits by modulating gene expression, thus altering the abundance of one or multiple proteins. Here we introduce a powerful strategy that integrates gene expression measurements with summary association statistics from large-scale genome-wide association studies (GWAS) to identify genes whose cis-regulated expression is associated with complex traits. We leverage expression imputation from genetic data to perform a transcriptome wide association study (TWAS) to identify significant expression-trait associations. We applied our approaches to expression data from blood and adipose tissue measured in ~ 3,000 individuals overall. We imputed gene expression into GWAS data from over 900,000 phenotype measurements to identify 69 new genes significantly associated with obesity-related traits (BMI, lipids and height). Many of these genes are associated with relevant phenotypes in the Hybrid Mouse Diversity Panel. Our results showcase the power of integrating genotype, gene expression and phenotype to gain insights into the genetic basis of complex traits. PMID- 26854920 TI - Leccinum vulpinum Watling induces DNA damage, decreases cell proliferation and induces apoptosis on the human MCF-7 breast cancer cell line. AB - The current work aimed to study the antitumour activity of a phenolic extract of the edible mushroom Leccinum vulpinum Watling, rich essentially in hydroxybenzoic acids. In a first approach, the mushroom extract was tested against cancer cell growth by using four human tumour cell lines. Given the positive results obtained in these initial screening experiments and the evidence of some studies for an inverse relationship between mushroom consumption and breast cancer risk, a detailed study of the bioactivity of the extract was carried out on MCF-7 cells. Once the selected cell line to precede the work was the breast adenocarcinoma cell line, the human breast non-malignant cell line MCF-10A was used as control. Overall, the extract decreased cellular proliferation and induced apoptosis. Furthermore, the results also suggest that the extract causes cellular DNA damage. Data obtained highlight the potential of mushrooms as a source of biologically active compounds, particularly with antitumour activity. PMID- 26854921 TI - Mechanism of diethylhexylphthalate (DEHP) induced testicular damage and of grape seed extract-induced protection in the rat. AB - The aim of this study was to determine the effect of diethylhexylphthalate (DEHP) on testicular mitochondrial viability and lipid peroxidation as a possible novel mechanism of PEHP testicular toxicity and whether grape seed extract (GSE) beneficially influences the mitochondrial function in testes of rats exposed to diethylhexylphthalate (DEHP). Sixty male albino rats were divided into three groups (n = 20): group I: was used as a control, group II: received diethylhexylphthalate (DEHP) (500 mg/kg/day orally) alone for 30 days, and group III: received the same DEHP dose in combination with GSE (proanthocyanidins) (100 mg/kg body weight). DEHP administration significantly decreases the testicular mitochondrial viability, mRNA expression of androgen receptors (AR), testosterone hormone concentration, increases mRNA expression of INOS and as compared to control group. It also decreases reduced glutathione (GSH) concentration, glutathione reductase (GR), super oxide dismutase (SOD), Catalase activities and increases lipid peroxidation (LPO) and DNA fragmentation%. In synchronization, a substantial decrease of testicular & epididymal weight and volume which accompanied by considerable alteration of semen character. Grape seed extract (GSE) alleviates the toxic effects of DEHP by increasing the mitochondrial viability, decreases the lipid peroxidation, and increases the testicular antioxidant activity. Our results were confirmed by histopathological and immunhistochemical studies. PMID- 26854922 TI - Ethanol and fatty acids impair lipid homeostasis in an in vitro model of hepatic steatosis. AB - Excess ethanol consumption and fatty acid intake lead to a cumulative effect on liver steatosis through still unclear mechanisms. This study aimed to characterize the lipid homoeostasis alterations under the exposure of hepatocytes to ethanol alone or combined with fatty acids. FaO hepatoma cells were incubated in the absence (C) or in the presence of 100 mM ethanol (EtOH) or 0.35 mM oleate/palmitate (FFA) alone or in the combination (FFA/EtOH). Content of intra- and extra-cellular triglycerides (TAGs) and of lipid droplets (LDs), expression of lipogenic and lipolytic genes, and oxidative stress-related parameters were evaluated. Exposure to either FFAs or EtOH given separately led to steatosis which was augmented when they were combined. Our results show that FFA/EtOH: (i) increased the LD number, but reduced their size compared to separate treatments; (ii) up-regulated PPARgamma and SREBP-1c and down-regulated sirtuin-1 (SIRT1); (iii) impaired FFA oxidation; (iv) did not change lipid secretion and oxidative stress. Our findings indicate that one of the major mechanisms of the metabolic interference between ethanol and fat excess is the impairment of FFA oxidation, in addition to lipogenic pathway stimulation. Interestingly, ethanol combined with FFAs led to a shift from macrovesicular to microvesicular steatosis that represents a more dangerous condition. PMID- 26854918 TI - Quantitatively predictable control of Drosophila transcriptional enhancers in vivo with engineered transcription factors. AB - Genes are regulated by transcription factors that bind to regions of genomic DNA called enhancers. Considerable effort is focused on identifying transcription factor binding sites, with the goal of predicting gene expression from DNA sequence. Despite this effort, general, predictive models of enhancer function are currently lacking. Here we combine quantitative models of enhancer function with manipulations using engineered transcription factors to examine the extent to which enhancer function can be controlled in a quantitatively predictable manner. Our models, which incorporate few free parameters, can accurately predict the contributions of ectopic transcription factor inputs. These models allow the predictable 'tuning' of enhancers, providing a framework for the quantitative control of enhancers with engineered transcription factors. PMID- 26854923 TI - Negotiating role management through everyday activities: narratives in action of two stroke survivors and their spouses. AB - PURPOSE: To manage social roles is a challenging part of self-management post stroke. This study explored how stroke survivors act as role managers with their spouses in the context of everyday activities. METHOD: Two stroke survivors with a first time stroke living at home with a spouse were included. Data were generated through participant observations at their own environment at 3, 6, 9, 15 and 21 months post-discharge. The narrative analysis focused on the actions of participants. RESULTS: Daily activities can be understood as an arena where role management and a meaningful live is negotiated and co-constructed with others. Everyday activities gave stroke survivors and their spouses insight into stroke survivors' capacities in daily situations. This was sometimes empowering, and other times conflicting when a spouse had negative perceptions of the abilities of the stroke survivors. CONCLUSION: The findings add to the current understanding of self-management and role management with regard to how these are situated in everyday activities. Daily activities can help both spouses to reflect and understand about self-management, role management and comanagement in daily life. Moreover, observing stroke survivors in everyday situations provides professionals with concrete pictures of stroke survivors' performance and self management in interaction with their spouses. Implications for Rehabilitation Self-management is a dynamic process in which individuals actively manage a chronic condition and finally live a meaningful life with a long-term chronic condition; self-management can be divided into medical, role, and emotional management; comanagement is when individuals activate resources and use the capacities of other persons to manage a situation together. Self-management is situated in everyday activities. Everyday activities give stroke survivors and their partners impressions about stroke survivors' self-management abilities post stroke in an everyday context. Everyday activities give stroke survivors and their partners an arena where role management and a meaningful life are negotiated and coconstructed through doing. Observing stroke survivors in everyday situations provides professionals a concreter picture of stroke survivors' self-management and comanagement with their partners than can be obtained from an informal interview. PMID- 26854924 TI - Tunable Percolation in Semiconducting Binary Polymer Nanoparticle Glasses. AB - Binary polymer nanoparticle glasses provide opportunities to realize the facile assembly of disparate components, with control over nanoscale and mesoscale domains, for the development of functional materials. This work demonstrates that tunable electrical percolation can be achieved through semiconducting/insulating polymer nanoparticle glasses by varying the relative percentages of equal-sized nanoparticle constituents of the binary assembly. Using time-of-flight charge carrier mobility measurements and conducting atomic force microscopy, we show that these systems exhibit power law scaling percolation behavior with percolation thresholds of ~24-30%. We develop a simple resistor network model, which can reproduce the experimental data, and can be used to predict percolation trends in binary polymer nanoparticle glasses. Finally, we analyze the cluster statistics of simulated binary nanoparticle glasses, and characterize them according to their predominant local motifs as (p(i), p(1-i))-connected networks that can be used as a supramolecular toolbox for rational material design based on polymer nanoparticles. PMID- 26854926 TI - Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis. AB - Selenium is a trace element that is essential for human health and is incorporated into more than 25 human selenocysteine-containing (Sec-containing) proteins via unique Sec-insertion machinery that includes a specific, nuclear genome-encoded, transfer RNA (tRNA[Ser]Sec). Here, we have identified a human tRNA[Ser]Sec mutation in a proband who presented with a variety of symptoms, including abdominal pain, fatigue, muscle weakness, and low plasma levels of selenium. This mutation resulted in a marked reduction in expression of stress related, but not housekeeping, selenoproteins. Evaluation of primary cells from the homozygous proband and a heterozygous parent indicated that the observed deficit in stress-related selenoprotein production is likely mediated by reduced expression and diminished 2'-O-methylribosylation at uridine 34 in mutant tRNA[Ser]Sec. Moreover, this methylribosylation defect was restored by cellular complementation with normal tRNA[Ser]Sec. This study identifies a tRNA mutation that selectively impairs synthesis of stress-related selenoproteins and demonstrates the importance of tRNA modification for normal selenoprotein synthesis. PMID- 26854925 TI - ART influences HIV persistence in the female reproductive tract and cervicovaginal secretions. AB - The recently completed HIV prevention trials network study 052 is a landmark collaboration demonstrating that HIV transmission in discordant couples can be dramatically reduced by treating the infected individual with antiretroviral therapy (ART). However, the cellular and virological events that occur in the female reproductive tract (FRT) during ART that result in such a drastic decrease in transmission were not studied and remain unknown. Here, we implemented an in vivo model of ART in BM/liver/thymus (BLT) humanized mice in order to better understand the ability of ART to prevent secondary HIV transmission. We demonstrated that the entire FRT of BLT mice is reconstituted with human CD4+ cells that are shed into cervicovaginal secretions (CVS). A high percentage of the CD4+ T cells in the FRT and CVS expressed CCR5 and therefore are potential HIV target cells. Infection with HIV increased the numbers of CD4+ and CD8+ T cells in CVS of BLT mice. Furthermore, HIV was present in CVS during infection. Finally, we evaluated the effect of ART on HIV levels in the FRT and CVS and demonstrated that ART can efficiently suppress cell-free HIV-RNA in CVS, despite residual levels of HIV-RNA+ cells in both the FRT and CVS. PMID- 26854927 TI - FOXE3 mutations predispose to thoracic aortic aneurysms and dissections. AB - The ascending thoracic aorta is designed to withstand biomechanical forces from pulsatile blood. Thoracic aortic aneurysms and acute aortic dissections (TAADs) occur as a result of genetically triggered defects in aortic structure and a dysfunctional response to these forces. Here, we describe mutations in the forkhead transcription factor FOXE3 that predispose mutation-bearing individuals to TAAD. We performed exome sequencing of a large family with multiple members with TAADs and identified a rare variant in FOXE3 with an altered amino acid in the DNA-binding domain (p.Asp153His) that segregated with disease in this family. Additional pathogenic FOXE3 variants were identified in unrelated TAAD families. In mice, Foxe3 deficiency reduced smooth muscle cell (SMC) density and impaired SMC differentiation in the ascending aorta. Foxe3 expression was induced in aortic SMCs after transverse aortic constriction, and Foxe3 deficiency increased SMC apoptosis and ascending aortic rupture with increased aortic pressure. These phenotypes were rescued by inhibiting p53 activity, either by administration of a p53 inhibitor (pifithrin-alpha), or by crossing Foxe3-/- mice with p53-/- mice. Our data demonstrate that FOXE3 mutations lead to a reduced number of aortic SMCs during development and increased SMC apoptosis in the ascending aorta in response to increased biomechanical forces, thus defining an additional molecular pathway that leads to familial thoracic aortic disease. PMID- 26854929 TI - T regulatory cell chemokine production mediates pathogenic T cell attraction and suppression. AB - T regulatory cells (Tregs) control immune homeostasis by preventing inappropriate responses to self and nonharmful foreign antigens. Tregs use multiple mechanisms to control immune responses, all of which require these cells to be near their targets of suppression; however, it is not known how Treg-to-target proximity is controlled. Here, we found that Tregs attract CD4+ and CD8+ T cells by producing chemokines. Specifically, Tregs produced both CCL3 and CCL4 in response to stimulation, and production of these chemokines was critical for migration of target T cells, as Tregs from Ccl3-/- mice, which are also deficient for CCL4 production, did not promote migration. Moreover, CCR5 expression by target T cells was required for migration of these cells to supernatants conditioned by Tregs. Tregs deficient for expression of CCL3 and CCL4 were impaired in their ability to suppress experimental autoimmune encephalomyelitis or islet allograft rejection in murine models. Moreover, Tregs from subjects with established type 1 diabetes were impaired in their ability to produce CCL3 and CCL4. Together, these results demonstrate a previously unappreciated facet of Treg function and suggest that chemokine secretion by Tregs is a fundamental aspect of their therapeutic effect in autoimmunity and transplantation. PMID- 26854928 TI - Temporal integration of light flashes by the human circadian system. AB - BACKGROUND: Beyond image formation, the light that is detected by retinal photoreceptors influences subcortical functions, including circadian timing, sleep, and arousal. The physiology of nonimage-forming (NIF) photoresponses in humans is not well understood; therefore, the development of therapeutic interventions based on this physiology, such as bright light therapy to treat chronobiological disorders, remains challenging. METHODS: Thirty-nine participants were exposed to 60 minutes of either continuous light (n = 8) or sequences of 2-millisecond light flashes (n = 31) with different interstimulus intervals (ISIs; ranging from 2.5 to 240 seconds). Melatonin phase shift and suppression, along with changes in alertness and sleepiness, were assessed. RESULTS: We determined that the human circadian system integrates flash sequences in a nonlinear fashion with a linear rise to a peak response (ISI = 7.6 +/- 0.53 seconds) and a power function decrease following the peak of responsivity. At peak ISI, flashes were at least 2-fold more effective in phase delaying the circadian system as compared with exposure to equiluminous continuous light 3,800 times the duration. Flashes did not change melatonin concentrations or alertness in an ISI-dependent manner. CONCLUSION: We have demonstrated that intermittent light is more effective than continuous light at eliciting circadian changes. These findings cast light on the phenomenology of photic integration and suggest a dichotomous retinohypothalamic network leading to circadian phase shifting and other NIF photoresponses. Further clinical trials are required to judge the practicality of light flash protocols. TRIAL REGISTRATION: Clinicaltrials.gov NCT01119365. FUNDING: National Heart, Lung, and Blood Institute (1R01HL108441 01A1) and Department of Veterans Affairs Sierra Pacific Mental Illness Research, Education, and Clinical Center. PMID- 26854930 TI - Chemokine receptor patterns in lymphocytes mirror metastatic spreading in melanoma. AB - Melanoma prognosis is dictated by tumor-infiltrating lymphocytes, the migratory and functional behavior of which is guided by chemokine or cytokine gradients. Here, we retrospectively analyzed the expression patterns of 9 homing receptors (CCR/CXCR) in naive and memory CD4+ and CD8+ T lymphocytes in 57 patients with metastatic melanoma (MMel) with various sites of metastases to evaluate whether T cell CCR/CXCR expression correlates with intratumoral accumulation, metastatic progression, and/or overall survival (OS). Homing receptor expression on lymphocytes strongly correlated with MMel dissemination. Loss of CCR6 or CXCR3, but not cutaneous lymphocyte antigen (CLA), on circulating T cell subsets was associated with skin or lymph node metastases, loss of CXCR4, CXCR5, and CCR9 corresponded with lung involvement, and a rise in CCR10 or CD103 was associated with widespread dissemination. High frequencies of CD8+CCR9+ naive T cells correlated with prolonged OS, while neutralizing the CCR9/CCL25 axis in mice stimulated tumor progression. The expansion of CLA-expressing effector memory CD8+ T cells in response to a single administration of CTLA4 blockade predicted disease control at 3 months in 47 patients with MMel. Thus, specific CCR/CXCR expression patterns on circulating T lymphocytes may guide potential diagnostic and therapeutic approaches. PMID- 26854931 TI - What You Don't Know: Improving Family Health History Knowledge among Multigenerational Families of Mexican Origin. AB - BACKGROUND: This study investigated diabetes and heart disease family health history (FHH) knowledge and changes after providing personalized disease risk feedback. METHODS: A total of 497 adults from 162 families of Mexican origin were randomized by household to conditions based on feedback recipient and content. Each provided personal and relatives' diabetes and heart disease diagnoses and received feedback materials following baseline assessment. Multivariate models were fitted to identify factors associated with the rate of 'don't know' FHH responses. RESULTS: At baseline, US nativity was associated with a higher 'don't know' response rate (p = 0.002). Though confounded by country of birth, younger age showed a trend toward higher 'don't know' response rates. Overall, average 'don't know' response rates dropped from 20 to 15% following receipt of feedback (p < 0.001). An intervention effect was noted, as 'don't know' response rates decreased more in households where one family member (vs. all) received supplementary risk assessments (without behavioral recommendations; p = 0.011). CONCLUSIONS: Limited FHH knowledge was noted among those born in the US and younger participants, representing a key population to reach with intervention efforts. The intervention effect suggests that 'less is more', indicating the potential for too much information to limit health education program effectiveness. PMID- 26854934 TI - Adult skin-derived precursor Schwann cells exhibit superior myelination and regeneration supportive properties compared to chronically denervated nerve derived Schwann cells. AB - Functional outcomes following delayed peripheral nerve repair are poor. Schwann cells (SCs) play key roles in supporting axonal regeneration and remyelination following nerve injury, thus understanding the impact of chronic denervation on SC function is critical toward developing therapies to enhance regeneration. To improve our understanding of SC function following acute versus chronic denervation, we performed functional assays of SCs from adult rodent sciatic nerve with acute- (Day 5 post) or chronic-denervation (Day 56 post), versus embryonic nerves. We also compared Schwann cells derived from adult skin-derived precursors (aSKP-SCs) as an accessible, autologous alternative to supplement the distal (denervated) nerve. We found that acutely-injured SCs and aSKP-SCs exhibited superior proliferative capacity, promotion of neurite outgrowth and myelination of axons, both in vitro and following transplant into a sciatic nerve crush injury model, while chronically-denervated SCs were severely impaired. Acute injury caused re-activation of transcription factors associated with an immature and pro-myelinating SC state (Oct-6, cJun, Sox2, AP2alpha, cadherin-19), but was diminished with prolonged denervation in vivo and could not be rescued following expansion in vitro suggesting that this is a permanent deficiency. Interestingly, aSKP-SCs closely resembled acutely injured and embryonic SCs, exhibiting elevated expression of these same transcription factors. In summary, prolonged denervation resulted in SC deficiency in several functional parameters that may contribute to impaired regeneration. In contrast, aSKP-SCs closely resemble the regenerative attributes ascribed to acutely-denervated or embryonic SCs emphasizing their potential as an accessible and autologous source of glia cells to enhance nerve regeneration, particularly following delays to surgical repair. PMID- 26854936 TI - Planar biaxial testing of soft biological tissue using rakes: A critical analysis of protocol and fitting process. AB - Mechanical characterization of soft biological tissue is becoming more and more prevalent. Despite the growing use of planar biaxial testing for soft tissue characterization, testing conditions and subsequent data analysis have not been standardized and vary widely. This also influences the quality of the result of the parameter fitting. Moreover, the testing conditions and data analysis are often not or incompletely reported, which impedes the proper comparison of parameters obtained from different studies. With a focus on planar biaxial tests using rakes, this paper investigates varying testing conditions and varying data analysis methods and their effect on the quality of the parameter fitting results. By means of a series of finite element simulations, aspects such as number of rakes, rakes' width, loading protocol, constitutive model, material stiffness and anisotropy are evaluated based on the degree of homogeneity of the stress field, and on the correlation between the experimentally obtained stress and the stress derived from the constitutive model. When calculating the aforementioned stresses, different definitions of the section width and deformation gradient are used in literature, each of which are looked into. Apart from this degree of homogeneity and correlation, also the effect on the quality of the parameter fitting result is evaluated. The results show that inhomogeneities can be reduced to a minimum for wise choices of testing conditions and analysis methods, but never completely eliminated. Therefore, a new parameter optimization procedure is proposed that corrects for the inhomogeneities in the stress field and induces significant improvements to the fitting results. Recommendations are made for best practice in rake-based planar biaxial testing of soft biological tissues and subsequent parameter fitting, and guidelines are formulated for reporting thereof in publications. PMID- 26854933 TI - Reducing synuclein accumulation improves neuronal survival after spinal cord injury. AB - Spinal cord injury causes neuronal death, limiting subsequent regeneration and recovery. Thus, there is a need to develop strategies for improving neuronal survival after injury. Relative to our understanding of axon regeneration, comparatively little is known about the mechanisms that promote the survival of damaged neurons. To address this, we took advantage of lamprey giant reticulospinal neurons whose large size permits detailed examination of post injury molecular responses at the level of individual, identified cells. We report here that spinal cord injury caused a select subset of giant reticulospinal neurons to accumulate synuclein, a synaptic vesicle-associated protein best known for its atypical aggregation and causal role in neurodegeneration in Parkinson's and other diseases. Post-injury synuclein accumulation took the form of punctate aggregates throughout the somata and occurred selectively in dying neurons, but not in those that survived. In contrast, another synaptic vesicle protein, synaptotagmin, did not accumulate in response to injury. We further show that the post-injury synuclein accumulation was greatly attenuated after single dose application of either the "molecular tweezer" inhibitor, CLR01, or a translation-blocking synuclein morpholino. Consequently, reduction of synuclein accumulation not only improved neuronal survival, but also increased the number of axons in the spinal cord proximal and distal to the lesion. This study is the first to reveal that reducing synuclein accumulation is a novel strategy for improving neuronal survival after spinal cord injury. PMID- 26854935 TI - Microscale tribological behavior and in vitro biocompatibility of graphene nanoplatelet reinforced alumina. AB - Graphene nanoplatelets were added as reinforcement to alumina ceramics in order to enhance microscale tribological behavior, which would be beneficial for ceramic-on-ceramic hip implant applications. The reduction in microscale wear is critical to hip implant applications where small amounts of wear debris can be detrimental to patients and to implant performance. The addition of the GNPs lead to improvements in fracture toughness and wear (scratch) resistance of 21% and 39%, respectively. The improved wear resistance was attributed to GNP-induced toughening, which generates fine (~100nm) microcracks on the scratch surface. In addition, active participation of GNPs was observed in the scratch subsurface of GNP-reinforced samples through focused ion beam sectioning. Friction coefficients are not significantly influenced by the addition of GNPs, and hence GNPs do not act as solid state lubricants. In vitro biocompatibility with human osteoblasts was assessed to evaluate any possible cytotoxic effects induced by GNPs. Osteoblast cells were observed to survive and proliferate robustly in the GNP reinforced samples, particularly those with high (10-15vol%) GNP content. PMID- 26854937 TI - Detection of bone marrow involvement in newly diagnosed post-transplant lymphoproliferative disorder: (18)F-fluorodeoxyglucose positron emission tomography/computed tomography versus bone marrow biopsy. AB - Detecting bone marrow involvement (BMI) in lymphoma is important as it adversely affects stage. Bone marrow biopsy (BMB) remains the standard to detect BMI but is prone to sampling error. We retrospectively investigated whether (18)F fluorodeoxyglucose positron emission tomography with computed tomography ((18)F FDG-PET/CT) could identify BMI in patients with post-transplant lymphoproliferative disorder (PTLD) with sufficient accuracy in comparison with staging BMB. Twenty-five patients diagnosed with PTLD who underwent (18)F-FDG PET/CT and BMB within one month were evaluated. Based on our criteria, six patients (24%) were considered positive for BMI on (18)F-FDG-PET/CT compared to one by BMB. Although we cannot completely exclude false positive results on (18)F FDG-PET/CT, our data indicate a significantly higher sensitivity of (18)F-FDG PET/CT compared to BMB (100% vs 17%) but similar specificity. These data confirm the high diagnostic performance of (18)F-FDG-PET/CT for detecting BMI, but prospective studies are needed to determine whether (18)F-FDG-PET/CT could indeed replace staging BMB in PTLD. PMID- 26854938 TI - Considerations for optimization of microRNA PCR assays for molecular diagnosis. AB - The remarkable stability of microRNAs in biofluids underlies their potential as biomarkers, but their small size presents challenges for detection by RT-qPCR. The heterogeneity of microRNAs, with each one comprising a series of variants or 'isomiRs', adds additional complexity. Presented here are the key considerations for use of RT-qPCR to measure microRNAs and their isomiRs, with a focus on plasma. Modified nucleotides can be incorporated into primer sequences to enhance affinity and provide increased specificity and sensitivity for RT-qPCR assays. Approaches based upon polyA tailing and use of a common oligo(dT)-based reverse transcription oligonucleotide will detect most isomiRs. Conversely, stem-loop RT oligonucleotides and sequence specific probes can enable detection of specific isomiRs of interest. Next generation sequencing of all the products of a microRNA RT-PCR reaction is a promising new approach for both microRNA quantification and characterization. PMID- 26854932 TI - Longitudinal measures of cognition in the Ts65Dn mouse: Refining windows and defining modalities for therapeutic intervention in Down syndrome. AB - Mouse models have provided insights into adult changes in learning and memory in Down syndrome, but an in-depth assessment of how these abnormalities develop over time has never been conducted. To address this shortcoming, we conducted a longitudinal behavioral study from birth until late adulthood in the Ts65Dn mouse model to measure the emergence and continuity of learning and memory deficits in individuals with a broad array of tests. Our results demonstrate for the first time that the pace at which neonatal and perinatal milestones are acquired is correlated with later cognitive performance as an adult. In addition, we find that life-long behavioral indexing stratifies mice within each genotype. Our expanded assessment reveals that diminished cognitive flexibility, as measured by reversal learning, is the most robust learning and memory impairment in both young and old Ts65Dn mice. Moreover, we find that reversal learning degrades with age and is therefore a useful biomarker for studying age-related decline in cognitive ability. Altogether, our results indicate that preclinical studies aiming to restore cognitive function in Ts65Dn should target both neonatal milestones and reversal learning in adulthood. Here we provide the quantitative framework for this type of approach. PMID- 26854940 TI - Rh-Doped Pt-Ni Octahedral Nanoparticles: Understanding the Correlation between Elemental Distribution, Oxygen Reduction Reaction, and Shape Stability. AB - Thanks to their remarkably high activity toward oxygen reduction reaction (ORR), platinum-based octahedrally shaped nanoparticles have attracted ever increasing attention in last years. Although high activities for ORR catalysts have been attained, the practical use is still limited by their long-term stability. In this work, we present Rh-doped Pt-Ni octahedral nanoparticles with high activities up to 1.14 A mgPt(-1) combined with improved performance and shape stability compared to previous bimetallic Pt-Ni octahedral particles. The synthesis, the electrocatalytic performance of the particles toward ORR, and atomic degradation mechanisms are investigated with a major focus on a deeper understanding of strategies to stabilize morphological particle shape and consequently their performance. Rh surface-doped octahedral Pt-Ni particles were prepared at various Rh levels. At and above about 3 atom %, the nanoparticles maintained their octahedral shape even past 30,000 potential cycles, while undoped bimetallic reference nanoparticles show a complete loss in octahedral shape already after 8000 cycles in the same potential window. Detailed atomic insight in these observations is obtained from aberration-corrected scanning transmission electron microscopy (STEM) and energy dispersive X-ray (EDX) analysis. Our analysis shows that it is the migration of Pt surface atoms and not, as commonly thought, the dissolution of Ni that constitutes the primary origin of the octahedral shape loss for Pt-Ni nanoparticles. Using small amounts of Rh we were able to suppress the migration rate of platinum atoms and consequently suppress the octahedral shape loss of Pt-Ni nanoparticles. PMID- 26854942 TI - Homophobic Violence, Coping Styles, Visibility Management, and Mental Health: A Survey of Flemish Lesbian, Gay, and Bisexual Individuals. AB - The understanding of how lesbians, gays, and bisexuals cope with homophobic violence is limited. Therefore, on the one hand, this study focuses on avoidance, problem-oriented, and emotion-oriented coping as general coping styles. On the other hand, special attention is paid to visibility management as a coping strategy that can be applied in a heteronormative context. Moreover, the moderating role of general coping styles and visibility management in the relationship between homophobic violence and negative mental health outcomes is studied. Data were collected from 1,402 Flemish lesbians, gays, and bisexuals. Stepwise regression analyses shows that coping styles and visibility management have a direct effect on mental health; however, no evidence for a moderating effect is found. Additionally, visibility management and emotion-oriented coping are found to exert a combined effect on mental health. PMID- 26854941 TI - Automated classification of brain tumor type in whole-slide digital pathology images using local representative tiles. AB - Computerized analysis of digital pathology images offers the potential of improving clinical care (e.g. automated diagnosis) and catalyzing research (e.g. discovering disease subtypes). There are two key challenges thwarting computerized analysis of digital pathology images: first, whole slide pathology images are massive, making computerized analysis inefficient, and second, diverse tissue regions in whole slide images that are not directly relevant to the disease may mislead computerized diagnosis algorithms. We propose a method to overcome both of these challenges that utilizes a coarse-to-fine analysis of the localized characteristics in pathology images. An initial surveying stage analyzes the diversity of coarse regions in the whole slide image. This includes extraction of spatially localized features of shape, color and texture from tiled regions covering the slide. Dimensionality reduction of the features assesses the image diversity in the tiled regions and clustering creates representative groups. A second stage provides a detailed analysis of a single representative tile from each group. An Elastic Net classifier produces a diagnostic decision value for each representative tile. A weighted voting scheme aggregates the decision values from these tiles to obtain a diagnosis at the whole slide level. We evaluated our method by automatically classifying 302 brain cancer cases into two possible diagnoses (glioblastoma multiforme (N = 182) versus lower grade glioma (N = 120)) with an accuracy of 93.1% (p << 0.001). We also evaluated our method in the dataset provided for the 2014 MICCAI Pathology Classification Challenge, in which our method, trained and tested using 5-fold cross validation, produced a classification accuracy of 100% (p << 0.001). Our method showed high stability and robustness to parameter variation, with accuracy varying between 95.5% and 100% when evaluated for a wide range of parameters. Our approach may be useful to automatically differentiate between the two cancer subtypes. PMID- 26854943 TI - Freestyle race pacing strategies (400 m) of elite able-bodied swimmers and swimmers with disability at major international championships. AB - Freestyle race pacing strategies (400 m) were compared between elite able-bodied swimmers and those with minimal physical (International Paralympic Committee S10 classification) and visual disabilities (International Paralympic Committee S13 classification). Data comprised 50-m lap splits and overall race times from 1176 400-m freestyle swims from World Championships, European Championships and Olympic/Paralympic Games between 2006 and 2012. Five pacing strategies were identified across groups (even, fast start, negative, parabolic and parabolic fast start), with negative and even strategies the most commonly adopted. The negative pacing strategy produced the fastest race times for all groups except for female S13 swimmers where an even strategy was most effective. Able-bodied groups swam faster than their S10 and S13 counterparts, with no differences between S10 and S13 groups. The results suggest adoption of multiple pacing strategies across groups, and even where impairments are considered minimal they are still associated with performance detriments in comparison to their able bodied counterparts. The findings have implications for the planning and implementation of training related to pacing strategies to ensure optimal swimmer preparation for competition. Analogous performance levels in S10 and S13 swimmers also suggest a case for integrated competition of these classifications in 400-m freestyle swimming. PMID- 26854944 TI - Proposal for a Pancreatic Configuration Index for Determining Patients at High Risk of Pancreatic Fistula Following Pancreatoduodenectomy. AB - BACKGROUND/AIMS: The pancreatic configuration is one of the most important factors that have an impact on the incidence of postoperative pancreatic fistula (POPF). This study sought to propose a new index, called the pancreatic configuration index (PCI), to categorize patients at a high risk for POPF. METHODS: Two hundred and thirty-one patients who underwent pancreatoduodenectomies were subjected to the analysis. The pancreatic parenchymal thickness and the main pancreatic duct (MPD) diameter at the pancreatic neck were measured using axial computed tomography scan images. The PCI was calculated by dividing the axial thickness by the MPD diameter. RESULTS: Sixty-two of the patients (26.8%) developed clinically significant POPF. Using a receiver operating characteristic curve analysis, the cut-off value of the PCI in predicting POPF was 5.3. The incidence of POFP increased depending on the PCI level. Using a multivariate analysis that included the various risk factors of POPF, a high PIC (>=5) was identified as an independent risk factor of POPF, with the highest OR at 6.50. CONCLUSION: The PCI is useful for stratifying patients at a high risk for POPFs. This index may be used to classify the patient population when evaluating other risk factors for POPF. PMID- 26854945 TI - A rapid solubility-optimized screening procedure for recombinant subtilisins in E. coli. AB - Subtilisins and other serine proteases are extensively used in the detergent, leather and food industry, and frequently under non-physiological conditions. New proteases with improved performance at extreme temperatures and in the presence of chemical additives may have great economical potential. The increasing availability of genetic sequences from different environments makes homology based screening an attractive strategy for discovery of new proteases. A prerequisite for large-scale screening of protease-encoding sequences is an efficient screening procedure. We have developed and implemented a screening procedure that encompasses cloning of candidate sequences into multiple expression vectors, cytoplasmic expression in E. coli, and a casein-based functional screen. The procedure is plate-format compatible and can be completed in only four days, starting from the gene of interest in a suitable cloning vector. The expression vector suite includes six vectors with combinations of maltose-binding protein (MBP) or the small ubiquitin-related modifier (SUMO) for increased solubility, and polyhistidine tags for downstream purification. We used enhanced green fluorescent protein and four Bacilli subtilisins to validate the screening procedure and our results show that proteins were expressed, soluble and active. Interestingly, the highest activities were consistently achieved with either MBP or SUMO fusions, thus demonstrating the merit of including solubility tags. In conclusion, the results demonstrate that our approach can be used to efficiently screen for new subtilisins, and suggest that the approach may also be used to screen for proteins with other activities. PMID- 26854946 TI - Complete genome sequence of a psychotrophic Arthrobacter strain A3 (CGMCC 1.8987), a novel long-chain hydrocarbons producer. AB - Arthrobacter strain A3, a psychotrophic bacterium isolated from the Tian Shan Mountain of China, can degrade the cellulose and synthesis the long-chain hydrocarbons efficiently in low temperature. Here we report the complete genome sequence of this bacterium. The complete genome sequence of Arthrobacter strain A3, consisting of a cycle chromosome with a size of 4.26 Mbp and a cycle plasmid with a size of 194kbp. In this genome, a hydrocarbon biosynthesis gene cluster (oleA, oleB/oleC and oleD) was identified. To resistant the extreme environment, this strain contains a unique mycothiol-biosynthetic pathway (mshA-D), which has not been found in other Arthrobacter species before. The availability of this genome sequence allows us to investigate the genetic basis of adaptation to growth in a nutrient-poor permafrost environment and to evaluate of the biofuel synthetic potential of this species. PMID- 26854947 TI - First complete genome sequence of a species in the genus Microterricola, an extremophilic cold active enzyme producing bacterial strain ERGS5:02 isolated from Sikkim Himalaya. AB - Here, we report the first ever complete genome sequence of any species in the genus Microterricola. The bacterium Microterricola viridarii ERGS5:02 isolated from the glacial stream of Sikkim Himalaya survived at low temperature and exhibited enhanced growth upon UV treatment, in addition, it also produced cold active enzymes. The complete genome assembly of 3.7 Mb suggested for the presence of genetic elements favoring the survival of bacterium under extreme conditions of UV and low temperature besides producing amylase, lipase and protease of industrial relevance. PMID- 26854948 TI - Enzymatic hydrolysis of poly(ethylene furanoate). AB - The urgency of producing new environmentally-friendly polyesters strongly enhanced the development of bio-based poly(ethylene furanoate) (PEF) as an alternative to plastics like poly(ethylene terephthalate) (PET) for applications that include food packaging, personal and home care containers and thermoforming equipment. In this study, PEF powders of various molecular weights (6, 10 and 40kDa) were synthetized and their susceptibility to enzymatic hydrolysis was investigated for the first time. According to LC/TOF-MS analysis, cutinase 1 from Thermobifida cellulosilytica liberated both 2,5-furandicarboxylic acid and oligomers of up to DP4. The enzyme preferentially hydrolyzed PEF with higher molecular weights but was active on all tested substrates. Mild enzymatic hydrolysis of PEF has a potential both for surface functionalization and monomers recycling. PMID- 26854949 TI - Pt, Co-Pt and Fe-Pt alloy nanoclusters encapsulated in virus capsids. AB - Nanostructured Pt-based alloys show great promise, not only for catalysis but also in medical and magnetic applications. To extend the properties of this class of materials, we have developed a means of synthesizing Pt and Pt-based alloy nanoclusters in the capsid of a virus. Pure Pt and Pt-alloy nanoclusters are formed through the chemical reduction of [PtCl4](-) by NaBH4 with/without additional metal ions (Co or Fe). The opening and closing of the ion channels in the virus capsid were controlled by changing the pH and ionic strength of the solution. The size of the nanoclusters is limited to 18 nm by the internal diameter of the capsid. Their magnetic properties suggest potential applications in hyperthermia for the Co-Pt and Fe-Pt magnetic alloy nanoclusters. This study introduces a new way to fabricate size-restricted nanoclusters using virus capsid. PMID- 26854950 TI - Pediatric Differentiated Thyroid Carcinoma of Follicular Cell Origin: Prognostic Significance of Histologic Subtypes. AB - BACKGROUND: Thyroid cancers are rare in the pediatric age group, and unlike in adults, few data are available regarding the clinical implication of histologic subtypes in the pediatric population. The purpose of the current study was to determine the prognostic significance of histologic subtypes of differentiated thyroid cancer (DTC) in a large series of children and adolescents followed at a single institution. METHODS: A retrospective review was conducted of all pediatric DTC patients who were treated and followed between 1988 and 2012. Sixty two patients (median age at diagnosis 13.8 years, median age at follow-up 18 years, 77% female) were assessed. The most common subtypes included classic papillary thyroid carcinoma (PTC; 48%), diffuse sclerosing PTC (16%), and follicular variant PTC (15%); 37% were considered "high-risk" histologies based on adult criteria. RESULTS: In a multivariate model, only extensive extrathyroidal extension (ETE), defined as the presence of two or more microscopic foci of tumor cells <=1 mm in size each or any foci >1 mm in size invading beyond the thyroid capsule into perithyroid soft tissue or organs, was significantly associated with extent of disease at presentation. At last follow up, 76% of subjects had no evidence of disease, 18% had persistent disease, and 5% had recurrent/progressive disease. Event-free survival was associated with extent of disease at presentation (p = 0.01), extensive ETE at diagnosis (p < 0.01), and male sex (p = 0.01), but not histologic subtype (p = 0.20). CONCLUSIONS: Pediatric DTC carries an excellent prognosis. Extensive ETE at diagnosis was found to be an independent predictor of extent of disease at presentation, as well as event-free survival. Unlike in the adult population, "high-risk" histologic subtypes did not independently predict extent of disease at presentation or event-free survival in this pediatric population with DTC. PMID- 26854953 TI - Applications of ion mobility mass spectrometry for high throughput, high resolution glycan analysis. AB - BACKGROUND: Diverse varieties of often heterogeneous glycans are ubiquitous in nature. They play critical roles in recognition events, act as energy stores and provide structural stability at both molecular and cellular levels. Technologies capable of fully elucidating the structures of glycans are far behind the other ' omic' fields. Liquid chromatography (LC) and mass spectrometry (MS) are currently the most useful techniques for high-throughput analysis of glycans. However, these techniques do not provide full unambiguous structural information and instead the gap in full sequence assignment is frequently filled by a priori knowledge of the biosynthetic pathways and the assumption that these pathways are highly conserved. SCOPE OF THE REVIEW: This comprehensive review details the rise of the emerging analytical technique ion mobility spectrometry (IMS) (coupled to MS) to facilitate the determination of three-dimensional shape: the separation and characterization of isobaric glycans, glyco(peptides/proteins), glycolipids, glycosaminoglycans and other polysaccharides; localization of sites of glycosylation; or interpretation of the conformational change to proteins upon glycan binding. MAJOR CONCLUSIONS: IMS is a highly promising new analytical route, able to provide rapid isomeric separation (ms timescale) of either precursor or product ions facilitating MS characterization. This additional separation also enables the deconvolution of carbohydrate MS(/MS) information from contaminating ions, improving sensitivity and reducing chemical noise. Derivation of collision cross sections (CCS) from IM-MS(/MS) data and subsequent calculations validate putative structures of carbohydrates from ab initio derived candidates. IM-MS has demonstrated that amounts of specific glycan isomers vary between disease states, which would be challenging to detect using standard analytical approaches. GENERAL SIGNIFICANCE: IM-MS is a promising technique that fills an important gap within the Glycomics toolbox, namely identifying and differentiating the three-dimensional structure of chemically similar carbohydrates and glycoconjugates. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. PMID- 26854954 TI - Microcalorimetry in the BioSciences-Principles and applications. PMID- 26854955 TI - Competitive binding of anticancer drugs 5-fluorouracil and cyclophosphamide with serum albumin: Calorimetric insights. AB - BACKGROUND: Isothermal titration calorimetry (ITC) has emerged as an excellent method to characterize drug-protein interactions. 5-Fluorouracil and cyclophosphamide have been used in combination for the treatment of breast carcinoma, though individually these drugs have also been useful in treating other types of cancer. A quantitative understanding of binding of these drugs with the transport protein under different conditions is essential for optimizing recognition by the protein and delivery at the target. METHODS: The values of binding constant, enthalpy, and entropy of binding have been determined by using ITC. Fluorescence and circular dichroism spectroscopies have been used to obtain further support to calorimetric observations, monitor conformational changes in the protein and establishing stoichiometry of association. RESULTS: The thermodynamic parameters have enabled a quantitative understanding of the affinity of 5-fluorouracil and cyclophosphamide with bovine serum albumin. The nature of binding has been unraveled based on effect of ionic strength, tetrabutyl-ammonium bromide, and sucrose which interfere in ionic, hydrophobic, and hydrogen bonding interactions. The binding site has been identified by using site marker warfarin in combination with 5-fluorouracil and cyclophosphamide. Further, the experiments have been done to establish whether both the drugs share the same binding site, and the effect of antibiotic drug carbenecillin and anti inflammatory drug naproxen on their association. GENERAL SIGNIFICANCE: Tuning optimum association of drugs with the transport vehicles for effective drug delivery requires identification of the nature of interacting groups in terms of energetics of interactions. Such studies employing ITC have direct significance in rational drug design. PMID- 26854957 TI - The early diagnostic value of C-reactive protein for anastomotic leakage post radical gastrectomy for esophagogastric junction carcinoma: A retrospective study of 97 patients. AB - BACKGROUND/AIMS: The incidence of esophagogastric junction (EGJ) carcinoma has increased worldwide. The only curable strategy for EGJ carcinoma is surgery, whereas anastomotic leakage is the major complication after operations. We aimed to test whether the serum levels of C-reactive protein have the diagnostic value for anastomotic leakage after surgery for EGJ carcinoma. METHODS: In this study, we analyzed the values of CRP before and 5 continuous days after surgery in 97 EGJ carcinoma patients who received surgery as the initial treatment. The levels of CRP in the groups of EGJ patients with or without anastomotic leakage were compared. RESULTS: The CRP levels of patients with anastomotic leakage elevated faster and remained higher compared patients without anastomotic leakage. The CRP value at Day 2 after radical surgery for EGJ carcinoma patients has the early diagnostic value for anastomotic leakage. The cut-off value of CRP for anastomotic leakage at Day 2 is 177 mg/l with the sensitivity of 0.9 and specificity of 0.95 (P < 0.0001). CONCLUSION: Surgical EGJ carcinoma patients with elevated CRP at Day 2 after surgery should be excluded the possibility of anastomotic leakage. PMID- 26854958 TI - Anterior approach versus posterior approach for Pipkin I and II femoral head fractures: A systemic review and meta-analysis. AB - PURPOSE: We performed a meta-analysis, pooling the results from controlled clinical trials to compare the efficiency of anterior and posterior surgical approaches to Pipkin I and II fractures of the femoral head. METHODS: Potential academic articles were identified from the Cochrane Library, Medline (1966 2015.5), PubMed (1966-2015.5), Embase (1980-2015.5) and ScienceDirect (1966 2015.5) databases. Gray studies were identified from the references of the included literature. Pooling of the data was performed and analyzed by RevMan software, version 5.1. RESULTS: Five case-control trials (CCTs) met the inclusion criteria. There were significant differences in the incidence of heterotopic ossification (HO) between the approaches, but no significant differences were found between the two groups regarding functional outcomes of the hip, general postoperative complications, osteonecrosis of the femoral head or post-traumatic arthritis. CONCLUSION: The present meta-analysis indicated that the posterior approach decreased the risk of heterotopic ossification compared with the anterior approach for the treatment of Pipkin I and II femoral head fractures. No other complications were related to anterior and posterior approaches. Future high-quality randomized, controlled trials (RCTs) are needed to determine the optimal surgical approach and to predict other postoperative complications. LEVEL OF EVIDENCE: III. PMID- 26854959 TI - Amyotrophic lateral sclerosis in Brazil: Case series and review of the Brazilian literature. AB - Our objective was to systematically analyse the first series of cases of amyotrophic lateral sclerosis (ALS) in Minas Gerais and to review the Brazilian literature about clinical studies in ALS. This was a cross-sectional and descriptive study of a consecutive series of patients with probable or defined sporadic ALS according to the Awaji criteria, followed at two referral centres of Belo Horizonte (South-east Brazil). Patients underwent full clinical assessment. Comparisons of patient subgroups according to disease duration and initial presentation were performed. A systematic review was performed about Brazilian clinical studies in ALS. Results showed that of the 61 enrolled patients the male/female ratio was 1.6:1. The mean age at onset of symptoms was 54.9 years (SD +/- 11.4). Mean age at diagnosis was 56.3 years (SD +/- 11.1). Regarding the initial form of presentation, 43 cases (70.5%) were spinal, 12 cases (19.7%) were generalized and six cases (9.8%) were bulbar. Eight studies were found in the systematic review. In conclusion, the profile of our sample was similar to other national and international series, except for fewer cases of bulbar ALS in our series. There are few clinical studies of ALS in Brazil. The national data of prevalence and incidence are still uncertain. PMID- 26854960 TI - Neurophysiology of spontaneous facial expressions: I. Motor control of the upper and lower face is behaviorally independent in adults. AB - Facial expressions are described traditionally as monolithic entities. However, humans have the capacity to produce facial blends, in which the upper and lower face simultaneously display different emotional expressions. This, in turn, has led to the Component Theory of facial expressions. Recent neuroanatomical studies in monkeys have demonstrated that there are separate cortical motor areas for controlling the upper and lower face that, presumably, also occur in humans. The lower face is represented on the posterior ventrolateral surface of the frontal lobes in the primary motor and premotor cortices and the upper face is represented on the medial surface of the posterior frontal lobes in the supplementary motor and anterior cingulate cortices. Our laboratory has been engaged in a series of studies exploring the perception and production of facial blends. Using high-speed videography, we began measuring the temporal aspects of facial expressions to develop a more complete understanding of the neurophysiology underlying facial expressions and facial blends. The goal of the research presented here was to determine if spontaneous facial expressions in adults are predominantly monolithic or exhibit independent motor control of the upper and lower face. We found that spontaneous facial expressions are very complex and that the motor control of the upper and lower face is overwhelmingly independent, thus robustly supporting the Component Theory of facial expressions. Seemingly monolithic expressions, be they full facial or facial blends, are most likely the result of a timing coincident rather than a synchronous coordination between the ventrolateral and medial cortical motor areas responsible for controlling the lower and upper face, respectively. In addition, we found evidence that the right and left face may also exhibit independent motor control, thus supporting the concept that spontaneous facial expressions are organized predominantly across the horizontal facial axis and secondarily across the vertical axis. PMID- 26854961 TI - The grounding of temporal metaphors. AB - Grounded cognition suggests that the processing of conceptual knowledge cued by language relies on the sensory-motor regions. Does temporal language similarly engage brain areas involved in time perception? Participants read sentences that describe the temporal extent of events with motion verbs (The hours crawled until the release of the news) and their static controls. Comparison conditions were fictive motion (The trail crawled until the end of the hills) and literal motion (The caterpillar crawled towards the top of the tree), along with their static controls. Several time sensitive locations, identified using a meta-analysis, showed activation specific to temporal metaphors, including in the left insula, right claustrum, and bilateral posterior superior temporal sulci. Fictive and literal motion contrasts did not show this difference. Fictive motion contrast showed activation in a conceptual motion sensitive area of the left posterior inferior temporal sulcus (ITS). These data suggest that language of time is at least partially grounded in experiential time. In addition, motion semantics has different consequences for events and objects: temporal events become animate, while static entities become motional. PMID- 26854962 TI - Single channel activity of OmpF-like porin from Yersinia pseudotuberculosis. AB - To gain a mechanistic insight in the functioning of the OmpF-like porin from Yersinia pseudotuberculosis (YOmpF), we compared the effect of pH variation on the ion channel activity of the protein in planar lipid bilayers and its binding to lipid membranes. The behavior of YOmpF channels upon acidification was similar to that previously described for Escherichia coli OmpF. In particular, a decrease in pH of the bathing solution resulted in a substantial reduction of YOmpF single channel conductance, accompanied by the emergence of subconductance states. Similar subconductance substates were elicited by the addition of lysophosphatidylcholine. This observation, made with porin channels for the first time, pointed to the relevance of lipid-protein interactions, in particular, the lipid curvature stress, to the appearance of subconductance states at acidic pH. Binding of YOmpF to membranes displayed rather modest dependence on pH, whereas the channel-forming potency of the protein tremendously decreased upon acidification. PMID- 26854964 TI - Moderators of response in exercise treatment for depression: A systematic review. AB - INTRODUCTION: Exercise have antidepressant effects in people with Major Depressive Disorder (MDD). However, about to half of patients do not respond to exercise. The identification of factors that moderates the antidepressant effects of exercise in people with MDD may help researchers and health professionals to identify sub-groups of patients that would benefit more from exercise. METHODS: A systematic review was carried out using Medline(PubMed), EMBASE and psycINFO up to April 2015. Individual and composite moderators were summarized and the strength of the evidence was assessed. RESULTS: Eleven studies were included for review resulting in the identification of potential individual (two biological, three clinical, two psychological and two social individual) and two potential composite moderators (the interaction between BDNF and Body Mass Index (BMI) and between family history of mental illness and gender). Only the two biological features and the BDNF x BMI interaction provided confirmatory evidence. LIMITATIONS: Due the different statistical approaches used in the studies, it was not possible to perform meta-analyses. The small number of studies and the exploratory nature of the evidence limits a wider generalization of the findings. CONCLUSION: Potential clinical, psychological, social or biological moderators were identified. However, the small number of studies and the limited strength of the evidence requires further studies before drawn definitive results. Further trials should consider the inclusion of moderators analysis using an a-priori, theoretical/evidence based hypothesis in order to provide high quality evidence for the use of personalized medicine in exercise for depression. PMID- 26854963 TI - Exploring chromatin organization mechanisms through its dynamic properties. AB - The organization of the genome in the nucleus is believed to be crucial for different cellular functions. It is known that chromosomes fold into distinct territories, but little is known about the mechanisms that maintain these territories. To explore these mechanisms, we used various live-cell imaging methods, including single particle tracking to characterize the diffusion properties of different genomic regions in live cells. Chromatin diffusion is found to be slow and anomalous; in vast contrast, depletion of lamin A protein significantly increases chromatin motion, and the diffusion pattern of chromatin transforms from slow anomalous to fast normal. More than this, depletion of lamin A protein also affects the dynamics of nuclear bodies. Our findings indicate that chromatin motion is mediated by lamin A and we suggest that constrained chromatin mobility allows to maintain chromosome territories. Thus, the discovery of this function of nucleoplasmic lamin A proteins sheds light on the maintenance mechanism of chromosome territories in the interphase nucleus, which ensures the proper function of the genome. PMID- 26854965 TI - Fatal outcome of human coronavirus NL63 infection despite successful viral elimination by IFN-alpha in a patient with newly diagnosed ALL. AB - INTRODUCTION: Human coronavirus NL63 (HCoV-NL63) is one of four common human respiratory coronaviruses. Despite high incidence, HCoV infections are grossly understudied. We here report a case of HCoV infection in a leukemia patient with fatal ARDS despite successful virus elimination by pegylated interferon-alpha (PEG-IFN-alpha). CASE: The 27-year-old female pre-T-ALL patient was treated according to the German-Multicenter Trial for Adult ALL protocol. No relevant infectious complications were seen until day 35 when the neutropenic patient developed fever without any clinical focus. Antibiotic prophylaxis was switched to meropenem. The patient deteriorated rapidly with respiratory failure due to ARDS. Anti-infectious therapy was escalated to additional linezolid and liposomal amphotericine-B. BAL revealed a significant viral load of HCoV-NL63. Based on successful application of PEG-IFN against the related SARS coronavirus in animal experiments, a single injection of 180 MUg PEG-IFN-alpha2b was applied. Despite immediate initiation of treatment and elimination of virus in subsequent tests, the progressive lung failure led to death 7 d after onset of fever with massive lung bleeding as a consequence of diffuse alveolar hemorrhage. CONCLUSION: This report emphasizes the fatal consequences of common respiratory virus infections in immunocompromised patients. HCoV-NL63 replication can be reduced by treatment with peg-IFN if diagnosed early. PMID- 26854966 TI - A novel ATM-dependent checkpoint defect distinct from loss of function mutation promotes genomic instability in melanoma. AB - Melanomas have high levels of genomic instability that can contribute to poor disease prognosis. Here, we report a novel defect of the ATM-dependent cell cycle checkpoint in melanoma cell lines that promotes genomic instability. In defective cells, ATM signalling to CHK2 is intact, but the cells are unable to maintain the cell cycle arrest due to elevated PLK1 driving recovery from the arrest. Reducing PLK1 activity recovered the ATM-dependent checkpoint arrest, and over-expressing PLK1 was sufficient to overcome the checkpoint arrest and increase genomic instability. Loss of the ATM-dependent checkpoint did not affect sensitivity to ionizing radiation demonstrating that this defect is distinct from ATM loss of function mutations. The checkpoint defective melanoma cell lines over-express PLK1, and a significant proportion of melanomas have high levels of PLK1 over expression suggesting this defect is a common feature of melanomas. The inability of ATM to impose a cell cycle arrest in response to DNA damage increases genomic instability. This work also suggests that the ATM-dependent checkpoint arrest is likely to be defective in a higher proportion of cancers than previously expected. PMID- 26854967 TI - TREM2 Function in Alzheimer's Disease and Neurodegeneration. AB - Alzheimer's disease (AD), the most common cause of dementia in the elderly, is a complex neurodegenerative disease marked by the appearance of amyloid-beta (Abeta) plaques and hyperphosphorylated tau tangles. Alzheimer's disease has a strong genetic component, and recent advances in genome technology have unearthed novel variants in several genes, which could provide insight into the pathogenic mechanisms that contribute to AD. Particularly interesting are variants in the microglial-expressed receptor TREM2 which are associated with a 2-4-fold increased risk of developing AD. Since the discovery of a link between TREM2 and AD, multiple studies have emerged testing whether partial or complete loss of TREM2 function contributed to Abeta deposition or Abeta-associated microgliosis. Although some confounding conflicting data have emerged from these studies regarding the role of TREM2 in regulating Abeta deposition within the hippocampus, the most consistent and striking observation is a strong decrease in microgliosis surrounding Abeta plaques in TREM2 haploinsufficient and TREM2 deficient mice. Interestingly, a similar impairment in microgliosis has been reported in mouse models of prion disease, stroke, and multiple sclerosis, suggesting a critical role for TREM2 in supporting microgliosis in response to pathology in the central nervous system. In this Review, we summarize recent reports on the role of TREM2 in AD pathology and hypothesized mechanisms by which TREM2 function could influence AD-induced microgliosis. PMID- 26854968 TI - What effect did the global financial crisis have upon youth wellbeing? Evidence from four Australian cohorts. AB - Recent research has suggested significant negative effects of the Global Financial Crisis (GFC) on mental health and wellbeing. In this article, the authors suggest that the developmental period of late adolescence may be at particular risk of economic downturns. Harmonizing 4 longitudinal cohorts of Australian youth (N = 38,017), we estimate the impact of the GFC on 1 general and 11 domain specific measures of wellbeing at age 19 and 22. Significant differences in wellbeing in most life domains were found, suggesting that wellbeing is susceptible to economic shocks. Given that the GFC in Australia was relatively mild, the finding of clear negative effects across 2 ages is of international concern. PMID- 26854969 TI - Chain Elongation with Reactor Microbiomes: Open-Culture Biotechnology To Produce Biochemicals. AB - Chain elongation into medium-chain carboxylates, such as n-caproate and n caprylate, with ethanol as an electron donor and with open cultures of microbial consortia (i.e., reactor microbiomes) under anaerobic conditions is being developed as a biotechnological production platform. The goal is to use the high thermodynamic efficiency of anaerobic fermentation to convert organic biomass or organic wastes into valuable biochemicals that can be extracted. Several liter scale studies have been completed and a first pilot-plant study is underway. However, the underlying microbial pathways are not always well understood. In addition, an interdisciplinary approach with knowledge from fields ranging from microbiology and chemical separations to biochemistry and environmental engineering is required. To bring together research from different fields, we reviewed the literature starting with the microbiology and ending with the bioprocess engineering studies that already have been performed. Because understanding the microbial pathways is so important to predict and steer performance, we delved into a stoichiometric and thermodynamic model that sheds light on the effect of substrate ratios and environmental conditions on product formation. Finally, we ended with an outlook. PMID- 26854970 TI - HbA1c is significantly associated with arterial stiffness but not with carotid atherosclerosis in a community-based population without type 2 diabetes: The Dong gu study. AB - OBJECTIVES: We examined the associations between HbA1c levels and various atherosclerotic vascular parameters among adults without diabetes from the general population. METHODS: A total of 6500 community-dwelling adults, who were free of type 2 diabetes and >=50 years of age, were included. High-resolution B mode ultrasound was used to evaluate carotid artery structure, including intima media thickness (IMT), plaque, and luminal diameter. Brachial-ankle pulse wave velocity (baPWV), which is a useful indicator of systemic arterial stiffness, was determined using an automatic waveform analysis device. RESULTS: No significant associations were observed between HbA1c, carotid IMT, plaque, or luminal diameter in a fully adjusted model. However, the odds ratio (95% confidence interval) for high baPWV (defined as the highest quartile) increased by 1.43 (1.19-1.71) per 1% HbA1c increase after adjusting for conventional risk factors in a multivariate logistic regression analysis. In addition, HbA1c was independently associated with baPWV in a multivariate linear regression analysis. CONCLUSIONS: High-normal HbA1c level was independently associated with arterial stiffness, but not with carotid atherosclerotic parameters, in the general population without diabetes. Our results suggest that the functional atherosclerotic process may already be accelerated according to HbA1c level, even at a level below the diagnostic threshold for diabetes. PMID- 26854971 TI - Effect of weight loss induced by energy restriction on measures of arterial compliance: A systematic review and meta-analysis. AB - AIM: To conduct a systematic review and meta-analysis of clinical trials involving adults, to determine the effect of weight loss induced by energy restriction with or without exercise, anti-obesity drugs or bariatric surgery on measures of arterial stiffness and compliance. METHODS: A systematic search of Pubmed, EMBASE, MEDLINE and the Cochrane Library was conducted to find intervention trials (randomised/non-randomised) that aimed to achieve weight loss and included the following outcome measures: cardio-ankle vascular index (CAVI), direct measures of area/diameter related to pressure change (including beta stiffness index, brachial or carotid artery compliance, aortic, carotid or brachial artery distensibility and strain), measures derived from peripheral pulse wave analysis (including augmentation index, augmentation pressure, distal oscillatory, proximal capacitive and systemic compliance) and pulse pressure. Data were analysed using Comprehensive Meta Analysis V2 using random effects analysis. Standardised mean difference (SMD) is reported with negative values indicating an improvement. RESULTS: A total of 43 studies, involving 4231 participants, were included in the meta-analysis. Mean weight loss was approximately 11% of initial body weight. Weight loss improved CAVI (SMD -0.48; p = 0.04), beta-stiffness index (SMD = -0.98; p = 0.001), arterial compliance (SMD = -0.61; p = 0.0001) and distensibility (SMD -1.10; p = 0.005), distal oscillatory compliance (SMD = -0.41; p = 0.03), proximal capacitive compliance (SMD -0.66; p = 0.009), systemic arterial compliance (SMD -0.71; p = 0.003) and reflection time (SMD -0.51; p = 0.001). Augmentation index, strain, augmentation pressure and pulse pressure were not significantly changed with weight loss. CONCLUSION: Weight loss induced by energy restriction improves some measures of arterial compliance and stiffness. PMID- 26854972 TI - Validation of coronary computed tomography angiography scores for non-invasive assessment of atherosclerotic burden through a comparison with multivessel intravascular ultrasound. AB - AIMS: While the atherosclerotic plaque volume can be manually quantified in coronary computed tomography angiography (CTA) it is impractical for clinical routine use. Several anatomical scores have been developed as surrogates for overall atherosclerotic burden in coronary CTA and even proven to be highly predictive for future adverse events. However, they have not been validated against the gold standard for atherosclerotic burden, intra-vascular ultrasound (IVUS). In the present study we have compared several coronary CTA scores with the coronary IVUS. METHODS AND RESULTS: A total of 62 patients with diagnosed coronary disease scheduled for percutaneous intervention were prospectively enrolled. For all patients, coronary CTA and multivessel IVUS were obtained. Calcium score and 6 previously reported scores were calculated from coronary CTA imaging and compared to average IVUS-derived percent atheroma volume (PAV). On average, 3.8 +/- 0.7 vessels, comprising 123.8 +/- 31.3 mm in length, were imaged with IVUS per patient. All but one previously described scoring systems showed a significant association with IVUS-derived PAV. Among them, the SSS score demonstrated the strongest correlation with IVUS-PAV (r = 0.61, p < 0.001) and the greatest area under the ROC curve (C-statistic = 0.87), to predict a high PAV. CONCLUSIONS: Most frequently used coronary CTA scores have a good correlation with global coronary atherosclerotic burden measured by multivessel IVUS derived atheroma volume. Among them, the SSS score shows the best performance being a good non-invasive alternative to IVUS for global coronary atherosclerotic burden assessment. PMID- 26854973 TI - Objectively measured physical activity and sedentary behaviour and ankle brachial index: Cross-sectional and longitudinal associations in older men. AB - BACKGROUND: Associations between bouts of physical activity (PA), sedentary behaviour (SB) and cardiovascular disease, and their mutual independence are not well defined. A low ankle brachial index (ABI <=0.9) indicates peripheral arterial disease (PAD) and is predictive of cardiovascular events and functional impairment. We investigated the independence of PA and SB and the importance of bout duration in relation to ABI using objective measures. METHODS: 945 men from the British Regional Heart Study, mean age 78.4 y, had concurrent measurements of ABI (Vicorder) and physical activity (Actigraph GT3X accelerometer); 427 men also had accelerometer measurements one year previously and contributed data to longitudinal analyses. RESULTS AND CONCLUSION: In cross-sectional analyses, after adjusting for covariates each extra 10 min of moderate and vigorous PA per day was associated with an OR of 0.81 (95% CI 0.72, 0.91) for a low ABI, a stronger association than for light PA (OR 0.85, 95% CI 0.75, 0.98). Each extra 30 min of SB was associated with an OR of 1.19 (95% CI 1.07, 1.33) for a low ABI. Associations between moderate and vigorous PA and ABI persisted after adjustment for light PA or SB. Bout lengths for PA and SB were not associated with a low ABI. One year changes in PA or SB were not associated with low ABI. All physical activity and lower levels of SB, regardless of bout duration were inversely associated with ABI; more intense PA showed a stronger association. No associations between changes in PA and ABI were observed, but power may have been limited. PMID- 26854974 TI - Fenofibrate, HDL, and cardiovascular disease in Type-2 diabetes: The DAIS trial. AB - BACKGROUND: There are conflicting reports on the role of fibrates in CVD-risk. Several studies indicate beneficial effects of fibrates on CVD risk in type-2 diabetic patients. We tested how fenofibrate changes lipoprotein subfractions and glucose homeostasis in type-2 diabetic patients. STUDY DESIGN: Selected markers of lipid and glucose homeostasis and inflammation were measured in 204 diabetic patients who participated in the Diabetes Atherosclerosis Intervention Study (DAIS) and were randomly assigned to 200 mg fenofibrate or placebo. Percent changes from baseline until a minimum of 3 years (average 39.6 months) on therapy (end of study) were calculated for all study parameters. RESULTS: The concentrations of total LDL-C and small dense LDL-C (sdLDL-C) did not change on fenofibrate compared to placebo. Compared to placebo, fenofibrate significantly decreased concentrations of triglyceride and remnant-like particle cholesterol (RLP-C) and activity of lipoprotein-associated phospholipase A2 (Lp-PLA2), while significantly increased concentrations of HDL-C. In contrast to other lipid modifying drugs (e.g. statins) which increase HDL-C by increasing large (alpha-1) HDL particles, fenofibrate increased HDL-C by increasing the smaller, less antiatherogenic HDL-C particles, alpha-3 and alpha-4. Furthermore, despite lowering TG levels by 20%, fenofibrate failed to decrease pre-beta1 levels. On fenofibrate, glycated serum-protein levels increased moderately, while insulin and adiponectin levels did not change. CONCLUSION: On fenofibrate, lipid homeostasis improved and Lp-PLA2 activity decreased while there was no improvement in glucose homeostasis. Despite increasing HDL-C and decreasing triglyceride levels, fenofibrate failed to improve the antiatherogenic properties of the HDL subpopulation profile. PMID- 26854976 TI - Distant effects of unilateral renal ischemia/reperfusion on contralateral kidney but not lung in rats: the roles of ROS and iNOS. AB - Acute kidney injury is usually associated with distant organ dysfunction. The roles of inducible nitric oxide synthase (iNOS) and reactive oxygen species (ROS) in this phenomenon were investigated following 2 h unilateral renal ischemia and 24 h reperfusion. There were 3 groups of rats subjected to either unilateral ischemia/reperfusion (UIR group), unilateral nephrectomy (UNX group), or sham operation. Two further groups were given alpha-tocopherol and aminoguanidine with UIR (treated-UIR group) and UNX (treated-UNX group). Plasma nitrite/nitrate and malondialdehyde were elevated only in the UIR group. Creatinine clearance and blood flow increased in non-ischemic kidney of the UIR, but not to the same extent as remnant kidney of the UNX group, while they had equal compensatory rises in absolute Na(+) and K(+) excretion and urine flow. Non-ischemic kidney of the treated-UIR group, but not remnant kidney of the treated-UNX group, showed more elevation in blood flow, whereas both kidneys had reductions in absolute Na(+) excretion and urine flow. Respiratory functional variable were not different between all groups. Therefore, 2 h unilateral renal ischemia and 24 h reperfusion did not affect lung but had distant effects on contralateral kidney partly mediated by ROS and NO-derived from iNOS to dampen compensatory increases in renal hemodynamics and to decrease tubular reabsorption. PMID- 26854978 TI - Ramping of pH Across the Water-Pool of a Reverse Micelle. AB - In this work, we have addressed the problem of "acidity" of the water-pool of a reverse micelle (RM) through the well-known inversion of sucrose reaction as a tool of investigation. This reaction has been performed inside positively and negatively charged RM and the rates are compared with that in bulk water. We propose that the buffer-like action in a water-pool is much stronger than expected earlier. The rate of sucrose hydrolysis slowed down in the negatively charged AOT reverse micelle while it sped up for the positively charged CTAB reverse micelle. However, temperature-dependent measurements showed that the activation energy remained the same for all the cases. It has been concluded that a proton gradient exists inside the water-pool of the reverse micelle and it determines the buffer-like action of the water-pool that persists until about 2 N of HCl in AOT RM of w(0) = 10.5. PMID- 26854977 TI - Protein Stability in Reverse Micelles. AB - The N-terminal SH3 domain of the Drosophila signal transduction protein drk was encapsulated in reverse micelles. Both the temperature of maximum stability and the melting temperature decreased on encapsulation. Dissecting the temperature dependent stability into enthalpic and entropic contributions reveals a stabilizing enthalpic and a destabilizing entropic contribution. These results do not match the expectations of hard-core excluded volume theory, nor can they be wholly explained by interactions between the head groups in the reverse micelle and the test protein. We suggest that geometric constraints imposed by the reverse micelles need to be considered. PMID- 26854979 TI - Changes in rat testis morphology and androgen receptor expression around the age of puberty. AB - BACKGROUND: Androgens are the keystone in fertility and intact sexual functions in males. It exerts its actions via androgen receptors extensively present in testicular cells, only its presence in germ cells is controversial. The alteration of androgen receptors in different testicular cells is usually accompanied by different sexual disorders. On the other hand, many sexual disorders are treated with androgens. Puberty, being the juncture of hormonal blossom, is an important stage to evaluate the evolution of testicular cells including androgen receptors. The aim of the work was to investigate the morphological and androgen receptor changes in different testicular cells during puberty in the rat testis using histological and immunohistochemical techniques. MATERIAL AND METHODS: This study was carried out on 45 male albino rats (Sprague Dawley). The rats were divided into three age groups; group I (prepubertal) 21 days old, group II (peripubertal) 35 days and group III (postpubertal) 90 days old. The rat testes were examined histologically and immuneohistochemically. Cells and androgen receptors were counted using Leica Qwin 500 image analyzer computer system. Data were analyzed using univariate ANOVA and Bonferroni post hoc test. RESULTS: Histological examination of the different ages showed developmental changes of different testicular cells. Immunohistochemical examination revealed the presence of AR in spermatogenic cells in pubertal and postpubertal groups and partially in prepubertal group. AR was clearly expressed in both Sertoli and Leydig cells in the three groups. The maximum expression in Sertoli cells was at 90 days while that of Leydig cells was at the age of 35 days. CONCLUSION: Androgen receptors should not be excluded as an effective factor on germ cells through its direct action on AR, clearly expressed in spermatogenic cells and its surge at the age of puberty. Studies and treatments should respect the AR expected levels according to age in other testicular cells as well. Sertoli cells show a linear increase of AR expression throughout life, while Leydig cells show a peak at the age of puberty. PMID- 26854981 TI - Synthesis and Bioactivity of Novel Trisubstituted Triazole Nucleosides. AB - A series of novel trisubstituted 1,2,3-triazole purine nucleosides were efficiently synthesized via Huisgen 1,3-dipolar cycloaddition in good yields. Bioactivity against cytomegalovirus (CMV) and varicella-zoster virus (VZV) in human embryonic lung cell cultures was evaluated and all compounds show low antiviral activity. PMID- 26854982 TI - Ligand Aspect Ratio as a Decisive Factor for the Self-Assembly of Coordination Cages. AB - It is possible to control the geometry and the composition of metallasupramolecular assemblies via the aspect ratio of their ligands. This point is demonstrated for a series of iron- and palladium-based coordination cages. Functionalized clathrochelate complexes with variable aspect ratios were used as rod-like metalloligands. A cubic Fe(II)8L12 cage was obtained from a metalloligand with an intermediate aspect ratio. By increasing the length or by decreasing the width of the ligand, the self-assembly process resulted in the clean formation of tetrahedral Fe(II)4L6 cages instead of cubic cages. In a related fashion, it was possible to control the geometry of Pd(II)-based coordination cages. A metalloligand with a large aspect ratio gave an entropically favored tetrahedral Pd(II)4L8 assembly, whereas an octahedral Pd(II)6L12 cage was formed with a ligand of the same length but with an increased width. The aspect ratio can also be used to control the composition of dynamic mixtures of Pd(II) cages. Out of two metalloligands with only marginally different aspect ratios, one gave rise to a self-sorted collection of Pd(II)4L8 and Pd(II)6L12 cages, whereas the other did not. PMID- 26854980 TI - SPATA7: Evolving phenotype from cone-rod dystrophy to retinitis pigmentosa. AB - BACKGROUND: SPATA7 mutations have been associated with different autosomal recessive retinal degeneration phenotypes. Long-term follow-up has not been described in detail. MATERIALS AND METHODS: A Hispanic patient with SPATA7 mutations was evaluated serially over a 12-year period with kinetic and static chromatic perimetry, optical coherence tomography (OCT), and fundus autofluorescence (AF) imaging. Electroretinography (ERG) was performed at the initial visit. RESULTS: The patient was homozygous for a mutation in SPATA7 (p.V458fs). At age 9, the ERG showed an abnormally reduced but preserved rod b wave and no detectable cone signals. There were two islands of vision: a midperipheral island with greater cone than rod dysfunction and a central island with normal cone but no rod function. Serial measures of rod and cone vision and co-localized retinal structure showed that the midperipheral island slowly became undetectable. By age 21, only the central island and its cone function remained, but it had become more abnormal in structure and function. CONCLUSION: The disease resulting from SPATA7 mutations in this patient initially presented as a cone-rod dystrophy (CRD), but changed over time into a phenotype more reminiscent of late-stage retinitis pigmentosa (RP). The differential diagnosis for both CRD and RP should include this rare molecular cause of autosomal retinal degeneration. An evolving phenotype complicates not only clinical diagnosis and patient counselling but also future strategies aimed at treating specific retinal regions. PMID- 26854983 TI - Response style and severity and chronicity of depressive disorders in primary health care. AB - BACKGROUND: Response styles theory of depression postulates that rumination is a central factor in occurrence, severity and maintaining of depression. High neuroticism has been associated with tendency to ruminate. We investigated associations of response styles and neuroticism with severity and chronicity of depression in a primary care cohort study. METHODS: In the Vantaa Primary Care Depression Study, a stratified random sample of 1119 adult patients was screened for depression using the Prime-MD. Depressive and comorbid psychiatric disorders were diagnosed using SCID-I/P and SCID-II interviews. Of the 137 patients with depressive disorders, 82% completed the prospective five-year follow-up with a graphic life chart enabling evaluation of the longitudinal course of episodes. Neuroticism was measured with the Eysenck Personality Inventory (EPI-Q). Response styles were investigated at five years using the Response Styles Questionnaire (RSQ-43). RESULTS: At five years, rumination correlated significantly with scores of Hamilton Depression Rating Scale (r=0.54), Beck Depression Inventory (r=0.61), Beck Anxiety Inventory (r=0.50), Beck Hopelessness Scale (r=0.51) and Neuroticism (r=0.58). Rumination correlated also with proportion of follow-up time spent depressed (r=0.38). In multivariate regression, high rumination was significantly predicted by current depressive symptoms and neuroticism, but not by anxiety symptoms or preceding duration of depressive episodes. CONCLUSIONS: Among primary care patients with depression, rumination correlated with current severity of depressive symptoms, but the association with preceding episode duration remained uncertain. The association between neuroticism and rumination was strong. The findings are consistent with rumination as a state-related phenomenon, which is also strongly intertwined with traits predisposing to depression. PMID- 26854984 TI - European Psychiatric Association Guidance on psychotherapy in chronic depression across Europe. AB - PURPOSE: Patients with chronic depression (CD) by definition respond less well to standard forms of psychotherapy and are more likely to be high utilizers of psychiatric resources. Therefore, the aim of this guidance paper is to provide a comprehensive overview of current psychotherapy for CD. The evidence of efficacy is critically reviewed and recommendations for clinical applications and research are given. METHODS: We performed a systematic literature search to identify studies on psychotherapy in CD, evaluated the retrieved documents and developed evidence tables and recommendations through a consensus process among experts and stakeholders. RESULTS: We developed 5 recommendations which may help providers to select psychotherapeutic treatment options for this patient group. The EPA considers both psychotherapy and pharmacotherapy to be effective in CD and recommends both approaches. The best effect is achieved by combined treatment with psychotherapy and pharmacotherapy, which should therefore be the treatment of choice. The EPA recommends psychotherapy with an interpersonal focus (e.g. the Cognitive Behavioural Analysis System of Psychotherapy [CBASP]) for the treatment of CD and a personalized approach based on the patient's preferences. DISCUSSION: The DSM-5 nomenclature of persistent depressive disorder (PDD), which includes CD subtypes, has been an important step towards a more differentiated treatment and understanding of these complex affective disorders. Apart from dysthymia, ICD-10 still does not provide a separate entity for a chronic course of depression. The differences between patients with acute episodic depression and those with CD need to be considered in the planning of treatment. Specific psychotherapeutic treatment options are recommended for patients with CD. CONCLUSION: Patients with chronic forms of depression should be offered tailored psychotherapeutic treatments that address their specific needs and deficits. Combination treatment with psychotherapy and pharmacotherapy is the first-line treatment recommended for CD. More research is needed to develop more effective treatments for CD, especially in the longer term, and to identify which patients benefit from which treatment algorithm. PMID- 26854985 TI - Self-reported symptoms of schizotypal and borderline personality disorder in patients with mood disorders. AB - BACKGROUND: Distinguishing between symptoms of schizotypal (SPD) and borderline personality disorders (BPD) is often difficult due to their partial overlap and frequent co-occurrence. We investigated correlations in self-reported symptoms of SPD and BPD in questionnaires at the levels of both total scores and individual items, examining overlapping dimensions. METHODS: Two questionnaires, the McLean Screening Instrument (MSI) for BPD and the Schizotypal Personality Questionnaire Brief (SPQ-B) for SPD, were filled in by patients with mood disorders (n=282) from specialized psychiatric care in a study of the Helsinki University Psychiatric Consortium. Correlation coefficients between total scores and individual items of the MSI and SPQ-B were estimated. Multivariate regression analysis (MRA) was conducted to examine the relationships between SPQ-B and MSI. RESULTS: The Spearman's correlation between total scores of the MSI and SPQ-B was strong (rho=0.616, P<0.005). Items of MSI reflecting disrupted relatedness and affective dysregulation correlated moderately (rphi varied between 0.2 and 0.4, P<0.005) with items of SPQ. Items of MSI reflecting behavioural dysregulation correlated only weakly with items of SPQ. In MRA, depressive symptoms, sex and MSI were significant predictors of SPQ-B score, whereas symptoms of anxiety, age and SPQ-B were significant predictors of MSI score. CONCLUSIONS: Items reflecting cognitive-perceptual distortions and affective symptoms of BPD appear to overlap with disorganized and cognitive-perceptual symptoms of SPD. Symptoms of depression may aggravate self-reported features of SPQ-B, and symptoms of anxiety features of MSI. Symptoms of behavioural dysregulation of BPD and interpersonal deficits of SPQ appear to be non-overlapping. PMID- 26854986 TI - BDNF Val66Met and clinical response to antipsychotic drugs: A systematic review and meta-analysis. AB - BACKGROUND: The polymorphic brain-derived neurotrophic factor (BDNF) gene has been postulated to be involved in inter-individual variability response to antipsychotic drugs. PURPOSE: To perform a qualitative and quantitative synthesis of studies evaluating the influence of BDNF genetic variation on clinical response to antipsychotics. METHODS: The review protocol was published in the PROSPERO database (Reg. n(o) CRD42015024614). A comprehensive search was performed through PubMed, Web of Knowledge and Cochrane databases up to July 2015. The methodological quality of identified studies was assessed using the MINORS criteria. Publication bias was estimated and potential sources of heterogeneity were investigated via meta-regression, subgroup and sensitivity analyses. RESULTS: Nine studies including a total of 2461 antipsychotic-treated patients fulfilled inclusion criteria for meta-analysis of BDNF Val66Met. Using the random-effects model, the pooled results showed no significant association with antipsychotic response for the dominant (Met carriers vs Val/Val, OR: 0.93, 95% CI: 0.72-1.19, P=0.55), codominant (Met/Met vs Val/Val, OR: 0.82, 95% CI: 0.59-1.15, P=0.25), recessive (Met/Met vs Val carriers, OR: 0.81, 95% CI 0.60 1.10, P=0.18) or the allelic contrast (Met vs Val, OR: 0.92, 95% CI 0.76-1.10, P=0.34). Visual inspection of funnel plots and further evaluation with Egger's test did not suggest evidence of publication bias. Despite lack of significant heterogeneity in most comparisons, no evidence of association also emerged in the subgroup and sensitivity analyses conducted. CONCLUSION: The present meta analysis excludes a clinically relevant effect of BDNF Val66Met on antipsychotic drug response per se. Nevertheless, further investigation is still needed to clarify in well-designed, large sample-based studies, the impact of BDNF haplotypes containing the Val66Met polymorphism. PMID- 26854987 TI - Reply by Authors. PMID- 26854988 TI - Reply by Authors. PMID- 26854989 TI - Editorial Comment. PMID- 26854990 TI - Editorial Comment. PMID- 26854991 TI - Editorial Comment. PMID- 26854992 TI - Editorial Comment. PMID- 26854975 TI - Degradable Controlled-Release Polymers and Polymeric Nanoparticles: Mechanisms of Controlling Drug Release. PMID- 26854993 TI - Orbital-Optimized MP3 and MP2.5 with Density-Fitting and Cholesky Decomposition Approximations. AB - Efficient implementations of the orbital-optimized MP3 and MP2.5 methods with the density-fitting (DF-OMP3 and DF-OMP2.5) and Cholesky decomposition (CD-OMP3 and CD-OMP2.5) approaches are presented. The DF/CD-OMP3 and DF/CD-OMP2.5 methods are applied to a set of alkanes to compare the computational cost with the conventional orbital-optimized MP3 (OMP3) [Bozkaya J. Chem. Phys. 2011, 135, 224103] and the orbital-optimized MP2.5 (OMP2.5) [Bozkaya and Sherrill J. Chem. Phys. 2014, 141, 204105]. Our results demonstrate that the DF-OMP3 and DF-OMP2.5 methods provide considerably lower computational costs than OMP3 and OMP2.5. Further application results show that the orbital-optimized methods are very helpful for the study of open-shell noncovalent interactions, aromatic bond dissociation energies, and hydrogen transfer reactions. We conclude that the DF OMP3 and DF-OMP2.5 methods are very promising for molecular systems with challenging electronic structures. PMID- 26854994 TI - Development and Evaluation of the Psychometric Properties of the CKD-MBD Knowledge and Behavior (CKD-MBD-KB) Questionnaire for Patients With Chronic Kidney Disease. AB - CONTEXT: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is one of the most complicated morbidities among patients with end-stage renal disease. At present, a specific questionnaire assessing relevant knowledge and behavior for patients with CKD-MBD is still unavailable. OBJECTIVES: To develop and evaluate a valid and reliable questionnaire specific to patients with CKD-MBD. METHODS: Both quantitative and qualitative analyses were combined to develop and estimate the CKD-MBD knowledge and behavior (CKD-MBD-KB) questionnaire. Three hundred thirteen and 295 patients, respectively, participated in the investigation during the period from November 2013~October 2014. Reliability and validity testing were conducted to analyze the psychometric properties of questionnaire. RESULTS: The final version of the CKD-MBD-KB questionnaire encompasses two domains, five facets, and 50 items. Reliability analysis showed that the Cronbach alpha of the five facets ranged from 0.578 to 0.854. Retest correlation coefficients of the five facets ranged from 0.825 to 0.944. Nine common factors were extracted from exploratory factor analysis that interpreted the cumulative variation of 64.1%, and factor loadings of all items were greater than 0.4. The results of confirmatory factor analysis indicated that the model had a satisfactory goodness of fit; the root mean square error of approximation = 0.070. Meanwhile, a significant correlation was found between each item and its facet. CONCLUSION: This CKD-MBD-KB questionnaire has been confirmed to have adequate psychometric properties (good reliability and validity) and may be useful in the assessment of patient-related knowledge, intervention programs, and treatment protocols. PMID- 26854995 TI - Adherence to Measuring What Matters Measures Using Point-of-Care Data Collection Across Diverse Clinical Settings. AB - CONTEXT: Measuring What Matters (MWM) for palliative care has prioritized data collection efforts for evaluating quality in clinical practice. How these measures can be implemented across diverse clinical settings using point-of-care data collection on quality is unknown. OBJECTIVES: To evaluate the implementation of MWM measures by exploring documentation of quality measure adherence across six diverse clinical settings inherent to palliative care practice. METHODS: We deployed a point-of-care quality data collection system, the Quality Data Collection Tool, across five organizations within the Palliative Care Research Cooperative Group. Quality measures were recorded by clinicians or assistants near care delivery. RESULTS: During the study period, 1989 first visits were included for analysis. Our population was mostly white, female, and with moderate performance status. About half of consultations were seen on hospital general floors. We observed a wide range of adherence. The lowest adherence involved comprehensive assessments during the first visit in hospitalized patients in the intensive care unit (2.71%); the highest adherence across all settings, with an implementation of >95%, involved documentation of management of moderate/severe pain. We observed differences in adherence across clinical settings especially with MWM Measure #2 (Screening for Physical Symptoms, range 45.7%-81.8%); MWM Measure #5 (Discussion of Emotional Needs, range 46.1%-96.1%); and MWM Measure #6 (Documentation of Spiritual/Religious Concerns, range 0-69.6%). CONCLUSION: Variations in clinician documentation of adherence to MWM quality measures are seen across clinical settings. Additional studies are needed to better understand benchmarks and acceptable ranges for adherence tailored to various clinical settings. PMID- 26854997 TI - Mechanisms of acquired long QT syndrome in patients with propionic academia. AB - BACKGROUND: Propionic acidemia (PROP) is a rare metabolic disorder caused by deficiency of propionyl-CoA carboxylase. PROP patients demonstrate QT prolongations associated with ventricular tachycardia and syncopes. Mechanisms responsible for this acquired long QT syndrome (acqLQTS) are unknown. OBJECTIVE: The aim of the study was to investigate acute and chronic effects of metabolites accumulating in PROP patients on major repolarizing potassium currents (IKs and IKr) and their channel subunits. METHODS: Voltage clamp studies were performed in CHO-KCNQ1/KCNE1 or HEK-KCNH2 cells to determine effects of propionic acid (PA; 1 10 mM), propionylcarnitine (PC; 25 uM-10 mM), methylcitrate (MC; 25 uM-10 mM), 0.2 M phosphate buffer (PB), or patient serum on IKs and IKr currents. Metabolite effects on action potentials were recorded in current clamp mode in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Protein expression of alpha- and beta-subunits of IKs (KCNQ1/KCNE1) and IKr (KCNH2) was evaluated with Western blots. RESULTS: Acute application of PA, PC, MC, and patient serum had no direct effect on net IKr densities (and KCNH2 expression), although it changed IKr gating kinetics. In contrast, PA, PC, MC, and patient serum all reduced IKs tail (-67% +/- 4.2%, -27% +/- 6.7%, -16% +/- 6.3%, -42.8% +/- 5.15; P < .001) and IKs-end pulse currents. PA significantly prolonged action potential duration (APD) in hiPSC-CM and QT interval in wild-type but not in LQT1 rabbits lacking IKs. Moreover, PC and MC (1 mM) decreased KCNQ1 protein expression (relative density: 0.58 +/- 0.08 and 0.16 +/- 0.05; P < .01). Chronic exposure to 10 mM PA, in contrast, increased KCNQ1 5.4-fold (P < .001) owing to decreased protein degradation. CONCLUSION: Acute reduction of IKs by PROP metabolites may be responsible for APD prolongation and acqLQTS observed in PROP patients. PMID- 26854998 TI - Maternal periodontitis decreases plasma membrane GLUT4 content in skeletal muscle of adult offspring. AB - AIMS: The fetal programming hypothesis suggests that intrauterine stimuli can induce metabolic changes in offspring, increasing the disease risk in adulthood. Periodontal disease may enhance serum cytokine levels. Cytokines such as tumor necrosis factor-alpha (TNF-alpha) have been associated with reduced glucose transporter type 4 (GLUT4) expression, decreased protein kinase B (Akt) phosphorylation, and insulin resistance. This study aimed to evaluate GLUT4 content, and Akt serine phosphorylation status in the gastrocnemius skeletal muscle (GSM), glycemia, insulinemia and change in body weight in offspring of rats with periodontal disease. MAIN METHODS: Female Wistar rats were distributed into a control group (CN) and an experimental periodontal disease group (PD), in which a ligature was placed around the mandibular first molars. Seven days after ligature placement, both groups were mated with normal male rats. The ligatures remained throughout pregnancy until weaning, after which the male offspring were distributed into groups: CN-o, control rat offspring; and PD-o, periodontal disease rat offspring. The body weight from 0 to 75days of age was measured. At 75days, the glycemia, insulinemia, TNF-alpha levels, Akt serine phosphorylation, and GLUT4 content in the GSM were measured in the offspring. KEY FINDINGS: The PD o group showed a low birth weight (LBW), unchanged glycemia, increased insulinemia, insulin resistance, increased TNF-alpha levels, decreased Akt serine phosphorylation status, and reduced GLUT4 content in the plasma membrane and translocation index after insulin stimulation. SIGNIFICANCE: Maternal periodontal disease causes LBW, insulin resistance, and alterations in the final stage of insulin signaling in the GSM of adult offspring. PMID- 26854999 TI - Therapeutic effects of dendrosomal solanine on a metastatic breast tumor. AB - AIMS: Our previous studies showed that alpha-solanine can inhibit tumor growth in cell culture and animal models of breast cancer. However, solanine is insoluble in common solvents; therefore, we developed a special nanoparticle with high capacity solubility. The present study is aimed to deliberate the therapeutic effects of dendrosomal solanine (DNS) on a metastatic breast tumor in vitro and in vivo. MAIN METHODS: After DNS preparation and dosing procedures, forty-five mice were equally divided into five groups to investigate the anti-metastatic effects of DNS on mammary tumor-bearing mice. KEY FINDINGS: Compared to solanine, DNS significantly suppressed the proliferation of 4 T1 cells in a dose- and time dependent manner. DNS showed a remarkable safety rate of up to 10mg/kg. A significant decrease in white blood-cell count was seen at 20mg/kg DNS in comparison with control animals. Mice treated with DNS had smaller tumor volume (mm(3)) in comparison with control and solanine groups. Moreover, the incidence of the breast tumor metastases was about 67% in the control animals, where as solanine and DNS 1mg/kg were about 22% and 0%, respectively. Furthermore, the number of metastases per mouse varied from one to three. The tissues of tumor, brain, liver, spleen, and lung showed higher expression levels of Bcl-2 but lower expression levels of Bax, MMP-2, MMP-9, mTOR, and Akt in DNS-treated mice than control and solanine groups. SIGNIFICANCE: The findings suggest that DNS has a more impactful therapeutic effect than solanine on 4 T1-induced breast tumorigenesis via influencing the tissue microenvironment. PMID- 26855000 TI - Environmental enrichment reverses cognitive impairments provoked by Western diet in rats: Role of corticosteroid receptors. AB - AIMS: Previous studies demonstrated that the Western diet (WD), which is rich in saturated fat (HFD) and refined sugar (HSU), is related to the impairments of hippocampus-dependent learning and memory and forebrain synaptic plasticity in rodents. The environmental enrichment (EE) has been shown to enhance learning and memory in the HFD-induced cognitive deficits, but the exact mechanism is still not clearly understood. Therefore, the present study aimed to clarify the effects of the EE on spatial memory in WD-fed rats, and to analyze the potential role of corticosteroid receptors in the EE conditioning. MAIN METHODS: Male Wistar albino rats were housed in either an enriched or standard environment and fed with the HFD (35% of energy as fat), HSU (100% of carbohydrate as sucrose) or standard rat chow for 4weeks. We used the Morris' water maze test (MWM) to assess the learning and memory performance, and measured plasma levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH), as well as glucocorticoid (GR) and mineralocorticoid receptor (MR) levels in the hippocampus. KEY FINDINGS: The results showed that HFD-fed rats displayed poorer learning and memory performance evaluated with MWM than controls. The EE reversed the cognitive deficits caused by the HFD. In addition, the EE resulted in an increase of GR and MR levels without affecting plasma CORT and ACTH concentrations. SIGNIFICANCE: Based on these findings, it could be suggested that the EE plays an important role in amelioration of the HFD-induced cognitive impairments, but this intervention is independent of the hypothalamic-pituitary-adrenal axis and hippocampal corticosteroid receptor levels. PMID- 26855001 TI - Protective effect of erythropoietin on myocardial apoptosis in rats exposed to carbon monoxide. AB - AIMS: Cardiac complications are common in carbon monoxide (CO) poisoning and associated with high morbidity and mortality. We have previously shown that erythropoietin (EPO) could reduce CO-induced cardiac ischemia in rat. In the current study, the anti-apoptotic effect of EPO during CO cardiotoxicity was investigated in order to elucidate the mechanism of EPO anti-ischemic action. MAIN METHODS: Wistar rats were exposed to CO (250, 1000 and 3000ppm). EPO (5000IU/kg) was administered to all groups by intraperitoneal injection at the end of CO exposure period. TUNEL and caspase-3 activity levels were assessed to investigate the effects of CO exposure and subsequent EPO administration on myocardial apoptosis. The changes of mitochondrial membrane potential (MMP) were also assessed with sensitive lipophilic dye JC-1 by flow cytometry. The roles of Bcl2 and Bax in EPO protective effect were investigated by Western blotting. KEY FINDINGS: Myocardial apoptosis was observed following CO exposure. Moreover, mitochondrial membrane depolarization and significant reduction in Bcl2/Bax ratio were shown following CO poisoning especially at 3000ppm. On the other hand, EPO administration could effectively suppress apoptosis in myocardial cells. Also, EPO significantly prevented the CO-induced depolarization of MMP (p<0.001) and preserved Bcl2/Bax ratio (p<0.01). SIGNIFICANCE: EPO reduces myocardial injury due to CO intoxication. Thus EPO could be suggested as a possible candidate for the management of CO cardiotoxicity with clinical applications. PMID- 26855002 TI - Constitutive expression Of NGF And P75(NTR) affected by bladder distension and NGF antisense treatment. AB - AIMS: It is known that bladder exposure to noxious stimuli elicits nerve growth factor (NGF) expression with region wise differences. Here, we investigated the effect of bladder distension (cystometry) and bladder wall injection of NGF antisense oligonucleotide (ODN) together as well as separately on spontaneous (constitutive) expression of NGF and its cognate p75 neurotrophin receptor (p75(NTR)). METHOD: Under isoflurane anesthesia, either 15MUg of protamine sulfate (vehicle) alone or complexed with 1.5MUg of NGF antisense or scrambled ODN was injected (10MUL) at 4 sites in bladder wall of 24 adult female Sprague Dawley rats and 6 rats were left untreated (n=30). Under urethane anesthesia, cystometry (CMG) was performed in treated and control rats. Fluorescent ODN and NGF/p75(NTR) expression was localized in harvested tissue. KEY FINDINGS: Complexation of ODN with protamine was essential for the retention of ODN in bladder tissue as the uncomplexed ODN was untraceable after injection. Bladder distension from CMG raised the expression of NGF and p75(NTR) relative to CMG naive rats. The groups treated with vehicle, scrambled and antisense ODN were indistinct with regard to CMG parameters, but the intense immunoreactivity of NGF and p75(NTR) seen in the vehicle and scrambled ODN groups was reduced following treatment with NGF antisense. SIGNIFICANCE: The constitutive expression of NGF and p75(NTR) is responsive to bladder distension and administration of NGF antisense. Complexation with protamine reduces the clearance of ODN and demonstrates the potential of ODN nanoparticles as an option for reducing the inducible NGF expression in OAB patients following intradetrusor injection. PMID- 26855004 TI - Three-Dimensional Bioprinting Materials with Potential Application in Preprosthetic Surgery. AB - Current methods in handling maxillofacial defects are not robust and are highly dependent on the surgeon's skills and the inherent potential in the patients' bodies for regenerating lost tissues. Employing custom-designed 3D printed scaffolds that securely and effectively reconstruct the defects by using tissue engineering and regenerative medicine techniques can revolutionize preprosthetic surgeries. Various polymers, ceramics, natural and synthetic bioplastics, proteins, biomolecules, living cells, and growth factors as well as their hybrid structures can be used in 3D printing of scaffolds, which are still under development by scientists. These scaffolds not only are beneficial due to their patient-specific design, but also may be able to prevent micromobility, make tension free soft tissue closure, and improve vascularity. In this manuscript, a review of materials employed in 3D bioprinting including bioceramics, biopolymers, composites, and metals is conducted. A discussion of the relevance of 3D bioprinting using these materials for craniofacial interventions is included as well as their potential to create analogs to craniofacial tissues, their benefits, limitations, and their application. PMID- 26855003 TI - Fetal exposure to placental corticotropin-releasing hormone is associated with child self-reported internalizing symptoms. AB - OBJECTIVE: Fetal exposure to maternal prenatal stress hormones such as cortisol exerts influences on the developing nervous system that persist and include risk for internalizing symptoms later in life. Placental corticotropin-releasing hormone (pCRH) is a feto-placental stress signal that also shapes fetal neurodevelopment and may be a more direct indicator of the fetal experience than maternal stress hormones. The programming effects of pCRH on child development are unknown. The current investigation examined associations between prenatal maternal and placental stress hormone exposures (maternal cortisol and pCRH) and child self-reported internalizing symptoms at age 5. METHOD: Maternal plasma cortisol and pCRH levels were measured at 15, 19, 25, 31, and 36 weeks' gestation in a sample of 83 women and their 91 children (8 sibling pairs from separate pregnancies), who were born full-term. Child self-reported internalizing symptoms at age 5 were obtained using scales of the Berkeley Puppet Interview. RESULTS: Placental CRH profiles (including elevations in mid-gestation) were associated with higher levels of internalizing symptoms at age 5. This effect was not explained by critical prenatal or postnatal influences, including obstetric risk, concurrent maternal psychological state, and family socio-economic status. Prenatal maternal cortisol was not significantly associated with child self reported internalizing symptoms. CONCLUSIONS: Findings suggest that elevated exposures to the feto-placental stress signal pCRH exert programming effects on the developing fetal central nervous system, with lasting consequences for child mental health. PMID- 26855006 TI - Intensity-modulated radiotherapy or volumetric-modulated arc therapy in patients with head and neck cancer: Focus on salivary glands dosimetry. AB - BACKGROUND: Despite radiotherapy (RT) technical improvements, high salivary dysfunction rates are still reported in patients with head and neck squamous cell carcinoma (HNSCC). The purpose of the present study was to report salivary glands dosimetry with volumetric-modulated arc therapy (VMAT) and intensity-modulated RT (IMRT). METHODS: Dosimetry of consecutive patients receiving IMRT or VMAT for proven HNSCC between 2007 and 2013 were retrospectively reviewed. RESULTS: Data of 609 patients were studied. Mean dose, mean maximum dose, and mean percentage of salivary gland volume receiving at least 26 Gy (V26) of the contralateral parotid were 24.50 Gy (range, 0-70.4 Gy), 39.08 Gy (range, 0.38-76.45 Gy), and 40.92% (range, 0% to 100%), respectively. Mean and maximum dose on contralateral submandibular gland were 48.18 Gy (range, 0.19-70.73 Gy), and 61.25 Gy (range, 0 75.8 Gy), respectively. CONCLUSION: Target volume coverage still has to be prioritized over organs at risk (OAR) sparing with new RT techniques. Submandibular glands are not sufficiently taken into account in guidelines. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 1028-1034, 2016. PMID- 26855007 TI - ABVD-Based Therapy for Hodgkin Lymphoma in Children and Adolescents: Lessons Learnt in a Tertiary Care Oncology Center in a Developing Country. AB - BACKGROUND: As Hodgkin lymphoma (HL) is a highly curable malignancy, most current pediatric trials focus on strategies aimed at reducing late effects of therapy. We report our results with doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) therapy. PROCEDURE: We retrospectively analyzed 17 years (1996-2013) data of patients <=18 years of age with HL. All patients received ABVD chemotherapy and involved field radiotherapy (IFRT) was reserved for those with bulky disease or partial response. The analysis was carried out to assess overall survival (OS) and freedom from treatment failure (FFTF) and factors predicting the events. RESULTS: Of 167 eligible patients, 72 (43.1%) had B symptoms, 28 (16.7%) had bulky disease, 31 (18.6%) had >4 lymph node regions, and 53 (31.8%) had advanced disease (stages III and IV). In all, 87% patients received six cycles of ABVD and IFRT was administered to 51 (30.5%) patients. The 5-year OS and FFTF were 95.9% and 79%, respectively, and were similar in patients treated with or without IFRT. On multivariable analysis, advanced disease (stages III and IV), involvement of >4 lymph node regions, and serum lactate dehydrogenase (LDH) >=500 IU/l at diagnosis were statistically significant factors for FFTF (P = 0.03, 0.003, 0.048, respectively). CONCLUSIONS: The excellent survival of HL patients in the setting of a developing country reported in this retrospective analysis warrants treatment reduction, especially for early-stage patients. The use of risk- and response-based stratification incorporating disease stage, involved lymph node regions, and serum LDH, along with fluorodeoxyglucose-positron emission tomography-based response, may guide development of effective and less toxic protocols. PMID- 26855005 TI - The T helper type 17/regulatory T cell paradigm in pregnancy. AB - T helper type 17 (Th17) and regulatory T (Treg) cells are active players in the establishment of tolerance and defence. These attributes of the immune system enmesh to guarantee the right level of protection. The healthy immune system, on the one hand, recognizes and eliminates dangerous non-self pathogens and, on the other hand, protects the healthy self. However, there are circumstances where this fine balance is disrupted. In fact, in situations such as in pregnancy, the foreign fetal antigens challenge the maternal immune system and Treg cells will dominate Th17 cells to guarantee fetal survival. In other situations such as autoimmunity, where the Th17 responses are often overwhelming, the immune system shifts towards an inflammatory profile and attacks the healthy tissue from the self. Interestingly, autoimmune patients have meliorating symptoms during pregnancy. This connects with the antagonist role of Th17 and Treg cells, and their specific profiles during these two immune challenging situations. In this review, we put into perspective the Th17/Treg ratio during pregnancy and autoimmunity, as well as in pregnant women with autoimmune conditions. We further review existing systems biology approaches that study specific mechanisms of these immune cells using mathematical modelling and we point out possible future directions of investigation. Understanding what maintains or disrupts the balance between these two opponent yet reciprocal cells in healthy physiological settings, sheds light into the development of innovative pharmacological approaches to fight pregnancy loss and autoimmunity. PMID- 26855008 TI - From global to regional and back again: common climate stressors of marine ecosystems relevant for adaptation across five ocean warming hotspots. AB - Ocean warming 'hotspots' are regions characterized by above-average temperature increases over recent years, for which there are significant consequences for both living marine resources and the societies that depend on them. As such, they represent early warning systems for understanding the impacts of marine climate change, and test-beds for developing adaptation options for coping with those impacts. Here, we examine five hotspots off the coasts of eastern Australia, South Africa, Madagascar, India and Brazil. These particular hotspots have underpinned a large international partnership that is working towards improving community adaptation by characterizing, assessing and projecting the likely future of coastal-marine food resources through the provision and sharing of knowledge. To inform this effort, we employ a high-resolution global ocean model forced by Representative Concentration Pathway 8.5 and simulated to year 2099. In addition to the sea surface temperature, we analyse projected stratification, nutrient supply, primary production, anthropogenic CO2 -driven ocean acidification, deoxygenation and ocean circulation. Our simulation finds that the temperature-defined hotspots studied here will continue to experience warming but, with the exception of eastern Australia, may not remain the fastest warming ocean areas over the next century as the strongest warming is projected to occur in the subpolar and polar areas of the Northern Hemisphere. Additionally, we find that recent rapid change in SST is not necessarily an indicator that these areas are also hotspots of the other climatic stressors examined. However, a consistent facet of the hotspots studied here is that they are all strongly influenced by ocean circulation, which has already shown changes in the recent past and is projected to undergo further strong change into the future. In addition to the fast warming, change in local ocean circulation represents a distinct feature of present and future climate change impacting marine ecosystems in these areas. PMID- 26855009 TI - Evaluating a health video on diabetic retinopathy. AB - Issue addressed Indigenous Australians are 14 times more likely than non Indigenous Australians to develop diabetic retinopathy (DR). Blindness can be prevented in 98% of cases if DR is identified and treated early. While the National Health and Medical Research Council recommend annual screening for Indigenous Australians, screening attendance rates remain low. The objective of this study was to evaluate whether a targeted health promotion intervention improved patient compliance and screening rates. Methods Bad Sugars, Bad Eyes - a culturally appropriate video targeting DR awareness and the importance of screening among Indigenous Australians - was developed at the Lions Eye Institute, Western Australia. The study used a patient questionnaire pre and post viewing of the video, as well as semi-structured interviews with Aboriginal Health Workers, to explore the influence the resource had on patient knowledge and attitudes. Eighty-four participants, currently involved in DR screening programs, were recruited from Aboriginal Medical Services (AMS) and Aboriginal Community Controlled Health Services (ACCHS). Results The video was found to increase patient knowledge about key DR issues as well as alter patient attitudes identified as potential barriers to screening. The areas most affected by the video resource were knowledge of recommended screening intervals, the severity of potential visual complications if DR is left undiagnosed and untreated and that screening is needed even when asymptomatic. Aboriginal Health Workers positively evaluated the video, all rating it as 'very' culturally appropriate, understandable and relatable. Conclusion The findings of this study suggest that Indigenous DR screening attendance rates could be increased through the expanded use of this video. So what? Indigenous DR screening attendance rates remain low, despite annual recommendations by the National Health and Medical Research Council. This gap needs to be addressed. PMID- 26855010 TI - Improved In Vitro and In Vivo Biocompatibility of Graphene Oxide through Surface Modification: Poly(Acrylic Acid)-Functionalization is Superior to PEGylation. AB - The unique physicochemical properties of two-dimensional (2D) graphene oxide (GO) could greatly benefit the biomedical field; however, recent research demonstrated that GO could induce in vitro and in vivo toxicity. We determined the mechanism of GO induced toxicity, and our in vitro experiments revealed that pristine GO could impair cell membrane integrity and functions including regulation of membrane- and cytoskeleton-associated genes, membrane permeability, fluidity and ion channels. Furthermore, GO induced platelet depletion, pro-inflammatory response and pathological changes of lung and liver in mice. To improve the biocompatibility of pristine GO, we prepared a series of GO derivatives including aminated GO (GO-NH2), poly(acrylamide)-functionalized GO (GO-PAM), poly(acrylic acid)-functionalized GO (GO-PAA) and poly(ethylene glycol)-functionalized GO (GO PEG), and compared their toxicity with pristine GO in vitro and in vivo. Among these GO derivatives, GO-PEG and GO-PAA induced less toxicity than pristine GO, and GO-PAA was the most biocompatible one in vitro and in vivo. The differences in biocompatibility were due to the differential compositions of protein corona, especially immunoglobulin G (IgG), formed on their surfaces that determine their cell membrane interaction and cellular uptake, the extent of platelet depletion in blood, thrombus formation under short-term exposure and the pro-inflammatory effects under long-term exposure. Overall, our combined data delineated the key molecular mechanisms underlying the in vivo and in vitro biological behaviors and toxicity of pristine GO, and identified a safer GO derivative that could be used for future applications. PMID- 26855011 TI - Identification and characterization of a novel intelectin in the digestive tract of Xenopus laevis. AB - The intelectin (Intl) family is a group of secretory lectins in chordates that serve multiple functions, including innate immunity, through Ca(2+)-dependent recognition of carbohydrate chains. Although six Intl family lectins have so far been reported in Xenopus laevis, none have been identified in the intestine. Using a monoclonal antibody to the Xenopus embryonic epidermal lectin (XEEL or Intl-1), I identified cross-reactive proteins in the intestines. The proteins were purified by affinity chromatography on a galactose-Sepharose column and found to be oligomers consisting of N-glycosylated 39 kDa and 40.5 kDa subunit peptides. N-terminal amino acid sequencing of these peptides, followed by cDNA cloning, identified two novel Intls (designated Intl-3 and Intl-4) that showed 59 79% amino acid identities with known Xenopus Intl family proteins. From the amino acid sequence, immunoreactivity, and properties of the recombinant protein, Intl 3 was considered the intestinal lectin identified by the anti-XEEL antibody. The purified Intl-3 protein could potentially bind to Escherichia coli and its lipopolysaccharides (LPS), and to Staphylococcus aureus and its peptidoglycans, depending on Ca(2+). In addition, the Intl-3 protein agglutinated E. coli cells in the presence of Ca(2+). Intraperitoneal injection of LPS increased the intestinal and rectal contents of Intl-3 and XCL-1 (or 35K serum lectin) proteins within three days; however, unlike XCL-1, Intl-3 was detectable in neither the sera nor the other tissues regardless of LPS stimulation. Immunohistochemical analyses revealed accumulation of the Intl-3 protein in mucus secretory granules of intestinal goblet cells. The results of this study suggest that Xenopus Intl-3 is involved in the innate immune protection of the digestive tract against bacterial infections. PMID- 26855012 TI - Role of eosinophils and apoptosis in PDIMs/PGLs deficient mycobacterium elimination in adult zebrafish. AB - The cell wall lipids phthiocerol dimycocerosates (PDIMs) and its structurally related compound, phenolic glycolipids (PGLs) are major virulence factors of mycobacterium, as shown by the reduced growth of PDIMs/PGLs deficient mutants in various animal models. PDIMs/PGLs play active roles in modulating host immune responses. However, the cellular and molecular mechanisms of how PDIMs/PGLs deficient mutant was eliminated in vivo are still elusive. Our aim was to investigate what host immune responses have effect on mycobacterium elimination in vivo. Using microarray, we find PDIMs/PGLs modulate divergent host responses, including chemotaxis and focal adhesion's downstream pathway and apoptosis. We examine these two host responses by Diff-Quik stain, coupled with transmission electron microscopy and TUNEL stain respectively. The ultrastructure observation showed that eosinophils appeared in WT-infected zebrafish at day 1, however eosinophils arrived was delayed to day 7 in PDIMs/PGLs-deficient mutant-infected animals. More intriguingly, apoptosis was markedly increased in PDIMs/PGLs-mutant infected zebrafish at day 1 after infection, compared to WT-infected fishes at this time. However, apoptosis trend was fully reversed by day 7, with increased apoptosis were detected in WT-infected zebrafish compared with the PDIMs/PGLs deficient mutant, especially more apoptosis within the granuloma. This study shows that the anti-apoptotic effects of PDIMs/PGLs and the recruitment of eosinophils in tissue during the early infection in zebrafish might promote bacterium growth in vivo. PMID- 26855013 TI - The known two types of transglutaminases regulate immune and stress responses in white shrimp, Litopenaeus vannamei. AB - Transglutaminases (TGs) play critical roles in blood coagulation, immune responses, and other biochemical functions, which undergo post-translational remodeling such as acetylation, phosphorylation and fatty acylation. Two types of TG have been identified in white shrimp, Litopenaeus vannamei, and further investigation on their potential function was conducted by gene silencing in the present study. Total haemocyte count (THC), differential haemocyte count (DHC), phenoloxidase activity, respiratory bursts (release of superoxide anion), superoxide dismutase activity, transglutaminase (TG) activity, haemolymph clotting time, and phagocytic activity and clearance efficiency to the pathogen Vibrio alginolyticus were measured when shrimps were individually injected with diethyl pyrocarbonate-water (DEPC-H2O) or TG dsRNAs. In addition, haemolymph glucose and lactate, and haemocytes crustin, lysozyme, crustacean hyperglycemic hormone (CHH), transglutaminaseI (TGI), transglutaminaseII (TGII) and clotting protein (CP) mRNA expression were determined in the dsRNA injected shrimp under hypothermal stress. Results showed that TG activity, phagocytic activity and clearance efficiency were significantly decreased, but THC, hyaline cells (HCs) and haemolymph clotting time were significantly increased in the shrimp which received LvTGI dsRNA and LvTGI + LvTGII dsRNA after 3 days. However, respiratory burst per haemocyte was significantly decreased in only LvTGI + LvTGII silenced shrimp. In hypothermal stress studies, elevation of haemolymph glucose and lactate was observed in all treated groups, and were advanced in LvTGI and LvTGI + LvTGII silenced shrimp following exposure to 22 degrees C. LvCHH mRNA expression was significantly up-regulated, but crustin and lysozyme mRNA expressions were significantly down-regulated in LvTGI and LvTGI + LvTGII silenced shrimp; moreover, LvTGII was significantly increased, but LvTGI was significantly decreased in LvTGI silenced shrimp following exposure to 28 and 22 degrees C. Knockdown of LvTGI and LvTGI + LvTGII also significantly increased the mortality of L. vannamei challenged with the pathogen V. alginolyticus. The same consequences have been confirmed in LvTGII silenced shrimp in our previous study. These results indicate that LvTGI and LvTGII not only reveal a complementary effect in gene expression levels but also play a key function in the immune defence mechanism of shrimp, by regulating the haemolymph coagulation, immune parameters and immune related gene expression, and in the regulation of carbohydrate metabolism. PMID- 26855014 TI - Comparison of immune response in Pacific white shrimp, Litopenaeus vannamei, after knock down of Toll and IMD gene in vivo. AB - The Toll and immune deficiency (IMD) pathways are essential for inducing immune related genes during invasion of pathogens. In the present study, transcripts of eight pathway-related genes in Litopenaeus vannamei, including Toll, IMD, Pelle, IAP1, TRAF6, ALF, Crustin and Penaeidin3 were analyzed to further understand the potential relationship between Toll and IMD pathway. The high transcription levels of TRAF6, Pelle, Toll, IMD and IAP1 in selected tissues indicates their functional roles in Toll and IMD pathways. The increased mRNA expression of Toll and IMD detected in the early stage might suggest the inducible role of Toll and IMD upon bacterial infection. Moreover, the continuous increase of IMD and the high level of Pelle and TRAF6 in Vibrio anguillarum challenged group indicated that Gram-negative bacterium can activate both the Toll and IMD signaling pathway. Silencing of Toll by a dsRNA-mediated RNAi strongly increased the transcripts of IMD, Pelle, TRAF6, IAP1 and Akirin, knocking down of IMD also markedly increased the transcripts of Toll, Pelle, IAP1 and Akirin. Furthermore, ALF expression was significantly increased in response to V. anguillarum and Micrococcus lysodeikticus challenge, while the transcripts of Crustin and Pen3 in hemocytes were significantly reduced in V. anguillarum group, but rose significantly following M. lysodeikticus infection. In summary, we speculate that Toll and IMD pathway are not independent in shrimp, but linked to defense against bacterial infection. PMID- 26855015 TI - From pathogens to microbiota: How Drosophila intestinal stem cells react to gut microbes. AB - The intestine acts as one of the interfaces between an organism and its external environment. As the primary digestive organ, it is constantly exposed to a multitude of stresses as it processes and absorbs nutrients. Among these is the recurring damage induced by ingested pathogenic and commensal microorganisms. Both the bacterial activity and immune response itself can result in the loss of epithelial cells, which subsequently requires replacement. In the Drosophila midgut, this regenerative role is fulfilled by intestinal stem cells (ISCs). Microbes not only trigger cell loss and replacement, but also modify intestinal and whole organism physiology, thus modulating ISC activity. Regulation of ISCs is integrated through a complex network of signaling pathways initiated by other gut cell populations, including enterocytes, enteroblasts, enteroendocrine and visceral muscles cells. The gut also receives signals from circulating immune cells, the hemocytes, to properly respond against infection. This review summarizes the types of gut microbes found in Drosophila, mechanisms for their elimination, and provides an integrated view of the signaling pathways that regulate tissue renewal in the midgut. PMID- 26855016 TI - A new subfamily of penaeidin with an additional serine-rich region from kuruma shrimp (Marsupenaeus japonicus) contributes to antimicrobial and phagocytic activities. AB - Penaeidins are an important family of antimicrobial peptides (AMPs) in penaeid shrimp. To date, five groups of penaeidins have been identified in penaeid shrimp. All are composed of a proline-rich N-terminus and a C-terminus containing six cysteine residues engaged in three disulfide bridges. In this study, a new type of penaeidin from Marsupenaeus japonicus was identified. The full-length penaeidin contains a unique serine-rich region and a penaeidin domain, which consists of a proline-rich region and a cysteine-rich region. Here, we classify all penaeidins into two subfamilies. All reported penaeidins are in subfamily I, and the new penaeidin identified in M. japonicus is designated as Penaeidin subfamily II (MjPen-II). MjPen-II was expressed in hemocytes, heart, hepatopancreas, gills, stomach and intestine, and was upregulated after bacterial challenge. A liquid bacteriostatic assay showed that MjPen-II had antibacterial activity to some Gram-positive and Gram-negative bacteria. MjPen-II could bind to bacteria by binding to polysaccharides on the surface of bacteria, thus promoting bacterial agglutination. The serine-rich region enhanced the agglutination activity of MjPen-II. The proline-rich domain had a stronger bacterial-binding activity and polysaccharide-binding activity than the cysteine-rich domain. MjPen II was also found to be involved in the phagocytosis of bacteria and efficiently improved the phagocytosis rate. Therefore, MjPen-II eliminates bacteria through direct bacterial inhibition as well as by promoting phagocytosis in shrimp. PMID- 26855017 TI - Catalytic Enantioselective Synthesis of Amino Skipped Diynes. AB - The Cu-catalyzed synthesis of nonracemic 3-amino skipped diynes via an enantiodetermining C-C bond formation is described using StackPhos as ligand. Despite challenging issues of reactivity and stereoselectivity inherent to these chiral skipped diynes, the reaction tolerates an extremely broad substrate scope with respect to all components and provides the title compounds in excellent enantiomeric excess. The alkyne moieties are demonstrated here to be useful synthetic handles, and 3-amino skipped diynes are convenient building blocks for enantioselective synthesis. PMID- 26855019 TI - Radiocarbon Analysis of Individual Amino Acids: Carbon Blank Quantification for a Small-Sample High-Pressure Liquid Chromatography Purification Method. AB - Compound-specific radiocarbon analysis (CSRA) of amino acids (AAs) is of great interest as a proxy for organic nitrogen (N) cycling rates, dating archeological bone collagen, and investigating processes shaping the biogeochemistry of global N reservoirs. However, recoverable quantities of individual compounds from natural samples are often insufficient for radiocarbon ((14)C) analyses (<50 MUg C). Constraining procedural carbon (C) blanks and their isotopic contributions is critical for reporting of accurate CSRA measurements. Here, we report the first detailed quantification of C blanks (including sources, magnitudes, and variability) for a high-pressure liquid chromatography (HPLC) method designed to purify individual AAs from natural samples. We used pairs of AA standards with either modern (M) or dead (D) fraction modern (Fm) values to quantify MC and DC blanks within several chromatographic regions. Blanks were determined for both individual and mixed AA standard injections with peak loadings ranging from 10 to 85 MUg C. We found 0.8 +/- 0.4 MUg of MC and 1.0 +/- 0.5 MUg of DC were introduced by downstream sample preparation (drying, combustion, and graphitization), which accounted for essentially the entire procedural blank for early eluting AAs. For late-eluting AAs, higher eluent organic content and fraction collected volumes contributed to total blanks of 1.5 +/- 0.75 MUg of MC and 3.0 +/- 1.5 MUg of DC. Our final measurement uncertainty for 20 MUg of C of most AAs was +/-0.02 Fm, although sample size requirements are larger for similar uncertainty in late-eluting AAs. These results demonstrate the first CSRA protocol for many protein AAs with uncertainties comparable to the lowest achieved in prior studies. PMID- 26855018 TI - LEADER-4: blood pressure control in patients with type 2 diabetes and high cardiovascular risk: baseline data from the LEADER randomized trial. AB - OBJECTIVE: As glucagon-like peptide-1 receptor agonists lower blood pressure (BP) in type 2 diabetes mellitus (T2DM), we examined BP control in relation to targets set by international bodies prior to randomization in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial. METHODS: We analyzed baseline data from LEADER (NCT01179048), an ongoing phase 3B, randomized, double-blind, placebo-controlled cardiovascular outcomes trial examining the cardiovascular safety of the glucagon-like peptide-1 receptor agonist liraglutide in 9340 people with T2DM from 32 countries [age (all mean +/- SD) 64 +/- 7.2 years, BMI 32.5 +/- 6.3 kg/m, duration of diabetes 12.7 +/- 8.0 years], all of whom were at high risk for cardiovascular disease (CVD). RESULTS: A total of 81% (n = 7592) of participants had prior CVD and 90% (n = 8408) had a prior history of hypertension. Despite prescription of multiple antihypertensive agents at baseline, only 51% were treated to a target BP of less than 140/85 mmHg and only 26% to the recommended baseline BP target of less than 130/80 mmHg. In univariate analyses, those with prior CVD were prescribed more agents (P < 0.001) and had lower BP than those without (137 +/- 18.8/78 +/- 10.6 mmHg versus 140 +/- 17.7/80 +/- 9.9 mmHg; P < 0.001). In logistic regression analyses, residency in North America (64% treated to <140/85 mmHg; 38% treated to <130/80 mmHg) was the strongest predictor of BP control. CONCLUSION: These contemporary data confirm that BP remains insufficiently controlled in a large proportion of individuals with T2DM at high cardiovascular risk, particularly outside North America. Longitudinal data from the LEADER trial may provide further insights into BP control in relation to cardiovascular outcomes in this condition. PMID- 26855020 TI - Cost Utility Analysis of the Cervical Artificial Disc vs Fusion for the Treatment of 2-Level Symptomatic Degenerative Disc Disease: 5-Year Follow-up. AB - BACKGROUND: The cervical total disc replacement (cTDR) was developed to treat cervical degenerative disc disease while preserving motion. OBJECTIVE: Cost effectiveness of this intervention was established by looking at 2-year follow up, and this update reevaluates our analysis over 5 years. METHODS: Data were derived from a randomized trial of 330 patients. Data from the 12-Item Short Form Health Survey were transformed into utilities by using the SF-6D algorithm. Costs were calculated by extracting diagnosis-related group codes and then applying 2014 Medicare reimbursement rates. A Markov model evaluated quality-adjusted life years (QALYs) for both treatment groups. Univariate and multivariate sensitivity analyses were conducted to test the stability of the model. The model adopted both societal and health system perspectives and applied a 3% annual discount rate. RESULTS: The cTDR costs $1687 more than anterior cervical discectomy and fusion (ACDF) over 5 years. In contrast, cTDR had $34 377 less productivity loss compared with ACDF. There was a significant difference in the return-to-work rate (81.6% compared with 65.4% for cTDR and ACDF, respectively; P = .029). From a societal perspective, the incremental cost-effective ratio (ICER) for cTDR was $165 103 per QALY. From a health system perspective, the ICER for cTDR was $8518 per QALY. In the sensitivity analysis, the ICER for cTDR remained below the US willingness-to-pay threshold of $50 000 per QALY in all scenarios (-$225 816 per QALY to $22 071 per QALY). CONCLUSION: This study is the first to report the comparative cost-effectiveness of cTDR vs ACDF for 2-level degenerative disc disease at 5 years. The authors conclude that, because of the negative ICER, cTDR is the dominant modality. ABBREVIATIONS: ACDF, anterior cervical discectomy and fusionAWP, average wholesale priceCE, cost-effectivenessCEA, cost-effectiveness analysisCPT, Current Procedural TerminologycTDR, cervical total disc replacementCUA, cost-utility analysisDDD, degenerative disc diseaseDRG, diagnosis related groupFDA, US Food and Drug AdministrationICER, incremental cost effectiveness ratioIDE, Investigational Device ExemptionNDI, neck disability indexQALY, quality-adjusted life yearsRCT, randomized controlled trialRTW, return to-workSF-12, 12-Item Short Form Health SurveyVAS, visual analog scaleWTP, willingness-to-pay. PMID- 26855021 TI - Potential roles of telocytes in lung diseases. AB - Telocytes (TCs) are a unique type of interstitial cells with specific, extremely long prolongations named telopodes (Tps), as shown by immune-positive staining against CD34, c-kit and vimentin. They were found in many organs of mammals, with potential biological functions, including the trachea and lung, even though the exact function remains unclear. Here, we give a historical overview of the TCs research field and summarize the latest findings associated with TCs, with a special focus on the recent progress about TCs specific gene and protein profiles that has been made in understanding that TCs may play a potential, but important, role in the pathogenesis of lung diseases. PMID- 26855022 TI - Levamisole adulterated cocaine and pulmonary vasculitis: Presentation of two lethal cases and brief literature review. AB - The first case reports of levamisole-related disease in cocaine users were published in 2010, although levamisole adulteration of cocaine was first recognized several years earlier. Currently, more than 70% of street cocaine seizures, in the US and the EU, contain levamisole, which could potentially be converted to aminorex, though the reasons for this practice still remain obscure. Here we report two fatal cases of isolated pulmonary vasculitis in abusers of levamisole-adulterated cocaine, where a complete autopsy, full toxicological analysis by gas chromatography-mass spectrometry (GC-MS) using a previously published method of Karch et al. and histological examination were performed. A control group composed of 11 cases of cocaine related deaths, where the presence of levamisole was excluded in blood, urine and hair, was used. Recent literature on the human pharmacokinetics of levamisole and aminorex is also reviewed. The toxicological analysis revealed positive qualitative and quantitative results for cocaine, benzoylecgonine and levamisole in both cases. In case 1 levamisole was found at the concentration of 13.5 and 61.3mg/L in blood and urine respectively, whereas in case 2 at 17.9 and 70.2mg/L. The histological examination highlighted in case 1 in heart samples microscopic evidence of the typical remodeling changes associated with chronic stimulant abuse, whereas lungs showed numerous lymphocytes surrounding and infiltrating the wall of small pulmonary vessels and a perivascular fibrosis with transforming fibroblasts. In case 2, the myocardial samples showed wide fields of myocardial necrosis characterized by hypercontraction of the myocytes with thickened Z-lines and short sarcomeres, whereas lung samples showed a significant intimal thickening of arteriole walls and lymphocytic infiltration of the wall and edema. Moreover, there were also numerous perivascular lymphocytic infiltrates. Although the pathological cardiac findings have allowed us to establish the cause of death in both cases, the presence of pulmonary vasculitis in the lungs represent a further complication. If the disease had progressed to hemorrhage, it certainly would have been a contributory cause of death. The two cases here reported allow us to advance a hypothesis about the possible correlation between the consumption of levamisole adulterated cocaine and pulmonary vasculitis and the comparison of these findings with the control group support this hypothesis. However, this hypothesis is still weak, taking into consideration the fact that pulmonary vasculitis was detected in 2 cases only, making it impossible to exclude a different etiology of this finding. Only through careful histological lung examinations of further cases of fatalities, related to levamisole adulterated cocaine, can this hypothesis be confirmed or refuted. PMID- 26855023 TI - Diethylstilbestrol Regulates the Expression of LGR8 in Mouse Gubernaculum Testis Cells. AB - BACKGROUND Hormonal effects on the gubernaculum can affect testicular descent. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the outgrowth of gubernaculums, leading to testis maldescent. However, the underlying mechanisms remain elusive. MATERIAL AND METHODS The gubernaculum were removed from 3-day-old mice and cultured. The subcultured cells were randomly divided into a normal control group and experimental groups. The DES groups were administered 10 MUg/ml, 1 MUg/ml, 0.1 MUg/ml, 0.01 MUg/ml of diethylstilbestrol dissolved in dimethyl sulfoxide (DMSO) respectively. The cell morphology was observed under an inverted microscope, and leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8) was localized by immunofluorescence. The expressions of LGR8 gene and protein in gubernaculum cells were quantified by RT PCR and Flow Cytometer respectively. RESULTS DES treatment converted cells from a normal fibroblast-like morphology into a more refractile, spindle-shaped morphology or irregular elliptical shapes along with cytoplasmic shrinkage. LGR8 was expressed in the cytoplasmic membrane, DES dose-dependently downregulated LGR8 expression at low doses (<=1.0 MUg/ml), but upregulated LGR8 at high doses (10 MUg/ml) at both the mRNA and protein levels. CONCLUSIONS These results suggest that DES causes testicular maldescent by altering the LGR8 pathway in mouse gubernaculum testis cells. PMID- 26855024 TI - The effect of upper limb casting on gait pattern. AB - Casting of the arm may interfere with normal walking patterns because of additional load of the cast or prevention of arm swing. This study aimed to determine the effect of applying various casts on temporospatial walking parameters, including gait velocity and cadence, step length, and single limb support. A computerized gait system was used to assess these variables for 23 healthy individuals in four walking modes: normal walking, with a cast above the elbow and a sling, and with a cast below the elbow, with and without a sling. Thirteen participants had their dominant hand casted and 10 had their nondominant hand casted. On average, casted participants took significantly smaller steps with the leg on the casted side and spent less time supported on the casted side. The least changes were noted with the arm in a cast below the elbow and no sling, and the greatest changes were noted with the arm in a cast above the elbow and in a sling. This difference was heightened when the dominant hand was casted and lessened when the nondominant hand was casted. No differences were found in walking velocity or cadence between the walking modes. Casting of the upper limb has significant effects on gait, which should be taken into consideration, especially in individuals with previous gait abnormalities. PMID- 26855025 TI - Recovery of Impaired Somatosensory Evoked Fields After Improvement of Tongue Sensory Deficits With Neurosurgical Reconstruction. AB - Somatosensory evoked fields (SEFs) induced by tongue stimulation can be useful as an objective parameter to assess sensory disturbances in the tongue. However, whether tongue SEFs can be useful as a clinical, objective follow-up assessment method of tongue sensation after oral surgery is unknown. We describe 2 cases in which tongue SEFs were successfully used in clinical assessment. Two patients with unilateral tongue sensory deficits caused by lingual nerve injury during lower third molar extraction were recruited. Both patients underwent surgery to repair the damaged nerve, and all tongue sensory evaluations were performed once before and once after surgery. SEFs were recorded by stimulating the affected and unaffected sides of the tongue separately, and cortical activity was evaluated over the contralateral hemisphere. The unilaterality of the deficit also was assessed. In both patients, stimulation of the unaffected side evoked reproducible cortical responses before and after surgery. Both patients also recovered some sensation after surgery, given that presurgery stimulation of the affected side failed to evoke cortical activity whereas postsurgery stimulation evoked cortical activity on both sides. Sensation was initially highly lateralized in both patients but was restored to approximately normal in the postsurgery evaluation. Finally, both patients rated their subjective tongue sensations on the affected side over 50% better after the surgical intervention. These cases indicate that tongue SEFs may have a clinical use as an objective parameter for assessing the course of tongue sensory recovery. PMID- 26855026 TI - Corrigendum: Epigenetic silencing of the XAF1 gene is mediated by the loss of CTCF binding. PMID- 26855027 TI - Design and Fabrication of Multifunctional Sericin Nanoparticles for Tumor Targeting and pH-Responsive Subcellular Delivery of Cancer Chemotherapy Drugs. AB - The severe cytotoxicity of cancer chemotherapy drugs limits their clinical applications. Various protein-based nanoparticles with good biocompatibility have been developed for chemotherapy drug delivery in hope of reducing drugs' side effects. Sericin, a natural protein from silk, has no immunogenicity and possesses diverse bioactivities that have prompted sericin's application studies. However, the potential of sericin as a multifunctional nanoscale vehicle for cancer therapy have not been fully explored. Here we report the successful fabrication and characterization of folate-conjugated sericin nanoparticles with cancer-targeting capability for pH-responsive release of doxorubicin (these nanoparticles are termed "FA-SND"). DOX is covalently linked to sericin through pH-sensitive hydrazone bonds that render a pH-triggered release property. The hydrophobicity of DOX and the hydrophilicity of sericin promote the self-assembly of sericin-DOX (SND) nanoconjugates. Folate (FA) is then covalently grafted to SND nanoconjugates as a binding unit for actively targeting cancer cells that overexpress folate receptors. Our characterization study shows that FA-SND nanoparticles exhibit negative surface charges that would reduce nonspecific clearance by circulation. These nanoparticles possess good cytotoxicity and hemocompatibiliy. Acidic environment (pH 5.0) triggers effective DOX release from FA-SND, 5-fold higher than does a neutral condition (pH 7.4). Further, FA-SND nanoparticles specifically target folate-receptor-rich KB cells, and endocytosed into lysosomes, an acidic organelle. The acidic microenvironment of lysosomes promotes a rapid release of DOX to nuclei, producing cancer specific chemo cytotoxicity. Thus, FA-mediated cancer targeting and lysosomal-acidity promoting DOX release, two sequentially-occurring cellular events triggered by the designed components of FA-SND, form the basis for FA-SND to achieve its localized and intracellular chemo-cytotoxicity. Together, this study suggests that these FA-SND nanoparticles may be a potentially effective carrier particularly useful for delivering hydrophobic chemotherapeutic agents for treating cancers with high level expression of folate receptors. PMID- 26855031 TI - A Welcome. PMID- 26855030 TI - The effect of dentine surface preparation and reduced application time of adhesive on bonding strength. AB - OBJECTIVE: This study evaluated the effects of surface preparation and the application time of adhesives on the resin-dentine bond strengths with universal adhesives. METHODS: Sixty molars were cut to exposed mid-coronal dentine and divided into 12 groups (n=5) based on three factors; (1) adhesive: G-Premio Bond (GP, GC Corp., Tokyo, Japan), Clearfil Universal Bond (CU, Kuraray Noritake Dental Inc., Okayama, Japan) and Scotchbond Universal Adhesive (SB, 3M ESPE, St. Paul, MN, USA); (2) smear layer preparation: SiC paper ground dentine or bur-cut dentine; (3) application time: shortened time or as manufacturer's instruction. Fifteen resin-dentine sticks per group were processed for microtensile bond strength test (MUTBS) according to non-trimming technique (1mm(2)) after storage in distilled water (37 degrees C) for 24h. Data were analyzed by three-way ANOVA and Dunnett T3 tests (alpha=0.05). Fractured surfaces were observed under scanning electron microscope (SEM). Another 12 teeth were prepared and cut into slices for SEM examination of bonded interfaces. RESULTS: MUTBS were higher when bonded to SiC-ground dentine according to manufacturer's instruction. Bonding to bur-cut dentine resulted in significantly lower MUTBS (p<0.000). Shortening the application time resulted in significantly lower bond strength for CU on SiC and GP on bur-cut dentine. SEM of fractured surfaces revealed areas with a large amount of porosities at the adhesive resin interface. This was more pronounced when adhesives were bonded with a reduced application time and on bur cut dentine. CLINICAL SIGNIFICANCE: The performance of universal adhesives can be compromised on bur cut dentine and when applied with a reduced application time. PMID- 26855033 TI - Treatment of Velopharyngeal Insufficiency: Fifteen-Year Experience at the University of Florida. AB - INTRODUCTION: A 15-year experience treating velopharyngeal insufficiency at the University of Florida is presented. After diagnostic speech evaluation, preoperative videofluoroscopy was the primary method used to evaluate the function of the velopharyngeal port. METHODS: Chart reviews of all patients with velopharyngeal insufficiency, including patients with failed palatal cleft surgery, submucous cleft palate, and noncleft palate who met study criteria were included. RESULTS: Overall success of treatment was 92%. Results are described by subgroups for further clarification. CONCLUSION: Selection of surgical procedure based on preoperative evaluation of velopharyngeal function and anatomy leads to a high rate of success. PMID- 26855029 TI - Apoptotic epithelial cells control the abundance of Treg cells at barrier surfaces. AB - Epithelial tissues continually undergo apoptosis. Commensal organisms that inhabit the epithelium influence tissue homeostasis, in which regulatory T cells (Treg cells) have a central role. However, the physiological importance of epithelial cell apoptosis and how the number of Treg cells is regulated are both incompletely understood. Here we found that apoptotic epithelial cells negatively regulated the commensal-stimulated proliferation of Treg cells. Gut commensals stimulated CX3CR1(+)CD103(-)CD11b(+) dendritic cells (DCs) to produce interferon beta (IFN-beta), which augmented the proliferation of Treg cells in the intestine. Conversely, phosphatidylserine exposed on apoptotic epithelial cells suppressed IFN-beta production by the DCs via inhibitory signaling mediated by the cell-surface glycoprotein CD300a and thus suppressed Treg cell proliferation. Our findings reveal a regulatory role for apoptotic epithelial cells in maintaining the number of Treg cell and tissue homeostasis. PMID- 26855034 TI - The Superior Rectal Artery as a Recipient Vessel for Free Flap Transfer After Partial Sacrectomy in Patients With Chordoma. AB - Free flaps have rarely been used to reconstruct lumbosacral defects, primarily because of the lack of suitable recipient vessels in this region. We propose the novel use of the superior rectal artery as a recipient vessel for free flap transfer after partial or total sacrectomy. We transferred free flow-through latissimus dorsi musculocutaneous flaps, with the superior rectal vessels as recipient vessels, to reconstruct defects after partial sacrectomy in 2 patients with sacral chordoma. The flaps survived completely, and the wounds healed uneventfully in both patients. The superior rectal artery is easier to dissect and anastomose than are gluteal vessels and is less affected by patients' postoperative postural change than are extraperitoneal vessels. We believe that the superior rectal artery is a versatile recipient vessel for free flap transfer to reconstruct sacrectomy defects. PMID- 26855035 TI - Improvement in Patient-Specific Outcomes After Carpal Tunnel Release in Patients Older Than 80 Years. AB - Outcomes after carpal tunnel release (CTR) may be influenced by age, disease chronicity, and disease severity. Multiple studies report mixed results between age and improvement through a validated instrument, the Brigham and Women's Carpal Tunnel Questionnaire (BWQ). However, these investigations did not control for confounders and had small cohorts of younger patients. We hypothesized that patients older than 80 years have statistically significant improvement in symptom severity and functional status after CTR. Patients completed the BWQ preoperatively and postoperatively. The main outcome measurement was difference in average BWQ scores, verified with Wilcoxon signed rank test. A standardized response mean was used to calculate effect size. Covariates were based on potential confounders, such as body mass index, hypothyroidism, American Society of Anesthesiologists (ASA) status, and thenar electromyography findings. The t test or chi test was used for univariate analysis. Logistical regression predicted odds of large versus small improvement in BWQ scores in a multivariate model, which was assessed with receiver operating characteristic and Hosmer Lemeshow tests. Statistically significant improvement was seen among the 44 patients who completed the BWQ, with symptom severity scores of 2.97 points; functional status scores, 1.52 points; and combined scores, 2.51 points. Age did not predict effect size; however, ASA status had a statistically significant inverse relation, with a decrease in the odds of large improvement by 77%. Age did not predict improvement in BWQ scores in a regression model analysis in 1 of the largest cohorts of patients older than 80 years who underwent CTR. Patients of this age do benefit from CTR. Although age is not associated with the size of this benefit, ASA status is associated, suggestive that other medical comorbidities adversely affect outcomes after CTR in this elderly population. PMID- 26855036 TI - Plastic Surgery Undergraduate Training: How a Single Local Event Can Inspire and Educate Medical Students. PMID- 26855028 TI - Enhancing the safety of antibody-based immunomodulatory cancer therapy without compromising therapeutic benefit: Can we have our cake and eat it too? AB - INTRODUCTION: Monoclonal antibodies (mAbs) targeting checkpoint inhibitors have demonstrated clinical benefit in treating patients with cancer and have paved the way for additional immune-modulating mAbs such as those targeting costimulatory receptors. The full clinical utility of these agents, however, is hampered by immune-related adverse events (irAEs) that can occur during therapy. AREAS COVERED: We first provide a general overview of tumor immunity, followed by a review of the two major classes of immunomodulatory mAbs being developed as cancer therapeutics: checkpoint inhibitors and costimulatory receptor agonists. We then discuss therapy-associated adverse events. Finally, we describe in detail the mechanisms driving their therapeutic activity, with an emphasis on interactions between antibody fragment crystallizable (Fc) domains and Fc receptors (FcR). EXPERT OPINION: Given that Fc-FcR interactions appear critical in facilitating the ability of immunomodulatory mAbs to elicit both therapeutically useful as well as adverse effects, the engineering of mAbs that can effectively engage their targets while limiting interaction with FcRs might represent a promising future avenue for developing the next generation of immune enhancing tumoricidal agents with increased safety and retention of efficacy. PMID- 26855037 TI - Single-Molecule Studies of Unlabeled Full-Length p53 Protein Binding to DNA. AB - p53 is an antitumor protein that plays an important role in apoptosis, preserving genomic stability and preventing angiogenesis, and it has been implicated in a large number of human cancers. For this reason it is an interesting target for both fundamental studies, such as the mechanism of interaction with DNA, and applications in biosensing. Here, we report a comprehensive study of label-free, full length p53 (flp53) and its interaction with engineered double-stranded DNA in vitro, at the single-molecule level, using atomic force microscopy (AFM) imaging and solid-state nanopore sensing. AFM data show that dimeric and tetrameric p53 bind to the DNA in a sequence-specific manner, confirming previously reported relative binding affinities. The statistical significance is tested using both the Grubbs test and stochastic simulations. For the first time, ultralow noise solid-state nanopore sensors are employed for the successful differentiation between bare DNA and p53/DNA complexes. Furthermore, translocation statistics reflect the binding affinities of different DNA sequences, in accordance with AFM data. Our results thus highlight the potential of solid-state nanopore sensors for single-molecule biosensing, especially when labeling is either not possible or at least not a viable option. PMID- 26855038 TI - Tissue-resident memory T cells in cytomegalovirus infection. AB - Herpesviruses establish life-long infection in their hosts and maintain latent reservoirs for sporadic reactivation at peripheral sites, such as skin and mucosae. For herpes simplex virus infection, experimental studies in mice revealed that immediate protection against local reactivation or superinfection events in the skin relies on tissue resident memory T cells (TRM) rather than on their circulating counterparts. Recent evidence extends this notion to cytomegalovirus infection, which potently induces TRM cells in both mice and humans particularly in mucosal tissues that constitute important viral sanctuaries and are relevant entry sites for challenge and superinfections. The discovery unravels promising opportunities to exploit cytomegalovirus based vaccine vectors for the specific induction of tissue resident T cell subsets. PMID- 26855039 TI - Middle East respiratory syndrome and severe acute respiratory syndrome. AB - The recent emergence of the Middle East respiratory syndrome (MERS)-CoV, a close relative of the Severe Acute respiratory syndrome (SARS)-CoV, both of which caused a lethal respiratory infection in humans, reinforces the need for further understanding of coronavirus pathogenesis and the host immune response. These viruses have evolved diverse strategies to evade and block host immune responses, facilitating infection and transmission. Pathogenesis following infection with these viruses is characterized by a marked delay in the induction of Type I interferon (IFN I) and, subsequently, by a poor adaptive immune response. Therapies that expedite IFN I induction as well as interventions that antagonize immunoevasive virus proteins are thus promising candidates for immune modulation. PMID- 26855040 TI - In vitro activity of Sorghum bicolor extracts, 3-deoxyanthocyanidins, against Toxoplasma gondii. AB - We investigated dried red leaf extracts of Sorghum bicolor for activity against Toxoplasma gondii tachyzoites. S. bicolor red leaf extracts were obtained by bioassay-guided fractionation using ethanol and ethyl acetate as solvents. Analysis of the crude and fractionated extracts from S. bicolor using electrospray ionization mass spectrometry (ESI-MS) showed that they contained significant amounts of apigeninidin, luteolinidin, 7-methoxyapigeninidin, 5 methoxyapigeninidin, 5-methoxyluteolinidin, 7-methoxyluteolinidin 5,7 dimethoxyapigeninidin or 5,7-dimethoxyluteolinidin, based on mass per charge (m/z). When tested in vitro, the IC50s for inhibitory activity against T. gondii tachyzoites' growth of the ethanol and ethyl acetate extracts were 2.3- and 4 fold, respectively, lower than their cytotoxic IC50s in mammalian cells. Ethyl acetate extracts fractionated in chloroform-methanol and chloroform had IC50s against T. gondii that were 56.1- and 3-fold lower than their respective cytotoxic IC50s in mammalian cells. These antiparasitic activities were found to be consistent with those of the respective pure 3-deoxyanthocyanidin compounds identified to be contained in the fractions in significant amounts. Further, we observed that, the position and number of methoxy groups possessed by the 3 deoyanthocyanidins influenced their antiparasitic activity. Together, our findings indicate that S. bicolor red-leaf 3-deoxyanthocyanidins-rich extracts have potent in vitro inhibitory activity against the proliferative stage of T. gondii parasites. PMID- 26855041 TI - Cost-effectiveness analysis of febuxostat in patients with gout in Spain. AB - Objectives Cost-effectiveness of febuxostat compared with allopurinol in the treatment of hyperuricemia in patients with gout. Methods Costs, clinical outcomes, and QALYs were estimated using a Markov model. Febuxostat 80 mg and 120 mg sequentially, used as first line and second line therapy, was compared with allopurinol 300 mg. Patients switched to the next treatment in the sequence according to a dichotomous response vs no response (target serum urate level < 6 mg/dl outcome) after 3 months of active treatment. A 3% discount rate and 5-year time horizon were applied. PERSPECTIVE: National Health System. Results The addition of febuxostat to any therapeutic strategy was an efficient option, with incremental cost-effectiveness ratios (ICER) compared with allopurinol 300 mg ranging from ?5268-?9737. Conclusions Febuxostat is a cost-effective treatment in Spain for the management of hyperuricemia in gout patients, with ICERs far below accepted Spanish efficiency thresholds (30 000?/QALY). PMID- 26855042 TI - Transfusion-related acute lung injury: transfusion, platelets and biological response modifiers. AB - Transfusion-related acute lung injury (TRALI) may be induced by plasma, platelet concentrates and red blood cell concentrates. The mechanism leading to TRALI is thought to involve two steps. The priming step consists of previous inflammatory pathological conditions or external factors attracting leukocytes to lung vessels and creating conditions favorable for the second step, in which anti-HLA or anti HNA antibodies or biologically active lipids, usually in transfused blood products, stress leukocytes and inflame lung epithelia. Platelets may be involved in the pathogenesis of TRALI because of their secretory potential and capacity to interact with other immune cells. There is no drug based-prophylaxis, but transfusion strategies are used to mitigate the risk of TRALI. PMID- 26855043 TI - Voltage Scaling of Graphene Device on SrTiO3 Epitaxial Thin Film. AB - Electrical transport in monolayer graphene on SrTiO3 (STO) thin film is examined in order to promote gate-voltage scaling using a high-k dielectric material. The atomically flat surface of thin STO layer epitaxially grown on Nb-doped STO single-crystal substrate offers good adhesion between the high-k film and graphene, resulting in nonhysteretic conductance as a function of gate voltage at all temperatures down to 2 K. The two-terminal conductance quantization under magnetic fields corresponding to quantum Hall states survives up to 200 K at a magnetic field of 14 T. In addition, the substantial shift of charge neutrality point in graphene seems to correlate with the temperature-dependent dielectric constant of the STO thin film, and its effective dielectric properties could be deduced from the universality of quantum phenomena in graphene. Our experimental data prove that the operating voltage reduction can be successfully realized due to the underlying high-k STO thin film, without any noticeable degradation of graphene device performance. PMID- 26855044 TI - Articulatory and Acoustic Characteristics of German Fricative Clusters. AB - BACKGROUND: We investigate the articulatory-acoustic relationship in German fricative sequences. We pursue the possibility that /f/#sibilant and /s#?/ sequences are in principle subject to articulatory overlap in a similar fashion, yet due to independent articulators being involved, there is a significant difference in the acoustic consequences. We also investigate the role of vowel context and stress. METHODS: We recorded electropalatographic and acoustic data from 9 native speakers of German. RESULTS: Results are compatible with the hypothesis that the temporal organization of fricative clusters is globally independent of cluster type with differences between clusters appearing mainly in degree. Articulatory overlap may be obscured acoustically by a labiodental constriction, similarly to what has been reported for stops. CONCLUSION: Our data suggest that similar principles of articulatory coordination underlie German fricative clusters independently of their segmental composition. The general auditory-acoustic patterning of the fricative sequences can be predicted by taking into account that aerodynamicacoustic consequences of gestural overlap may vary as a function of the articulators involved. We discuss possible sources for differences in degrees of overlap and place our results in the context of previously reported asymmetries among the fricatives in regressive place assimilation. PMID- 26855045 TI - Open-Wedge High Tibial Osteotomy: RCT 2 Years RSA Follow-Up. AB - We investigated the influence of three different bone grafting materials on stability and clinical outcome of the healing open-wedge high tibial osteotomy (OW-HTO) with immediate partial weight bearing. A total of 45 (3 * 15) patients were randomized to injectable calcium phosphate cement (Calcibon; Biomet-Merck Biomaterials GmbH, Darmstadt, Germany), local bone autograft, or iliac crest autograft. Stability of the bony healing was evaluated with radiostereometric analysis (RSA) up to 24 months postoperatively. Clinical outcome was evaluated with the knee injury and osteoarthritis outcome score (KOOS). RSA revealed translations and rotations close to zero regardless of bone grafting material, with no statistically significant differences between the groups. Clinically, the Calcibon group had lower quality of life KOOS subscore at 2 years follow-up. We conclude that with a stable implant and 6 weeks of partial weight bearing, local autografting is sufficient to achieve solid bone consolidation following OW-HTO. PMID- 26855046 TI - Unraveling the Link between Malnutrition and Adverse Clinical Outcomes: Association of Acute and Chronic Malnutrition Measures with Blood Biomarkers from Different Pathophysiological States. AB - BACKGROUND AND AIMS: Malnutrition is associated with poor clinical outcomes. Whether there is a causal relationship or it merely mirrors a severe patient condition remains unclear. We examined the association of malnutrition with biomarkers characteristic of different pathophysiological states to better understand the underlying etiological mechanisms. METHODS: We prospectively followed consecutive adult medical inpatients. Multivariable regression models were used to investigate the associations between malnutrition - as assessed using the Nutritional Risk Screening (NRS 2002) - and biomarkers linked to inflammation, stress, renal dysfunction, nutritional status and hematologic function. RESULTS: A total of 529 patients were included. In a fully adjusted model, malnutrition was significantly associated with the inflammatory markers procalcitonin (0.20, 95% CI 0.03-0.37), proadrenomedullin (0.28, 95% CI 0.12 0.43) and albumin (-0.39, 95% CI -0.57 to -0.21), the stress marker copeptin (0.34, 95% CI 0.17-0.51), the renal function marker urea (0.23, 95% CI 0.07 0.38), the nutritional markers vitamin D25 (-0.22, 95% CI -0.41 to -0.02) and corrected calcium (0.29, 95% CI 0.10-0.49) and the hematological markers hemoglobin (-0.27, 95% CI -0.43 to -0.10) and red blood cell distribution width (0.26, 95% CI 0.07-0.44). Subgroup analysis suggested that acute malnutrition rather than chronic malnutrition was associated with elevated biomarker levels. CONCLUSION: Acute malnutrition was associated with a pronounced inflammatory response and an alteration in biomarkers associated with different pathophysiological states. Interventional trials are needed to prove causality. PMID- 26855047 TI - Depletion of SAM50 Specifically Targets BCR-ABL-Expressing Leukemic Stem and Progenitor Cells by Interfering with Mitochondrial Functions. AB - A high proliferation rate of malignant cells requires an increased energy production, both by anaerobic glucose metabolism and mitochondrial respiration. Moreover, increased levels of mitochondria-produced reactive oxygen species (ROS) promote survival of transformed cells and contribute to the disease progression both in solid tumors and leukemia. Consequently, interfering with mitochondrial metabolism has been used as a strategy to specifically target leukemic cells. SAM50 is a mitochondrial outer membrane protein involved in the formation of mitochondrial intermembrane space bridging (MIB) complex. Although the importance of SAM50 in maintaining MIB integrity and in the assembly of mitochondrial respiratory chain complexes has been described, its specific role in the normal and leukemic hematopoietic cells remains unknown. We observed that human leukemic cells display a specific dependency on SAM50 expression, as downregulation of SAM50 in BCR-ABL-expressing, but not normal CD34(+) human hematopoietic stem and progenitor cells (HSPCs) caused a significant decrease in growth, colony formation, and replating capacity. Mitochondrial functions of BCR-ABL-expressing HSPCs were compromised, as seen by a decreased mitochondrial membrane potential and respiration. This effect of SAM50 downregulation was recapitulated in normal HSPCs exposed to cytokine-rich culture conditions that stimulate proliferation. Both oncogene-transduced and cytokine-stimulated HSPCs showed increased mitochondrial membrane potential and increased ROS levels compared to their normal counterparts. Therefore, we postulate that human leukemic HSPCs are highly dependent on the proper functioning of mitochondria and that disruption of mitochondrial integrity may aid in targeting leukemic cells. PMID- 26855048 TI - Employment for adults with autism spectrum disorders: A retrospective review of a customized employment approach. AB - Over the past few decades, there has been an increase in prevalence of children with autism spectrum disorders (ASD), and those children are now becoming young adults in need of competitive integrated employment (CIE). Customized employment (CE) is one pathway to employment that has been successful for other individuals with developmental disabilities (DD), though research has been very limited on the effectiveness with individuals with ASD. This paper provides a retrospective review of 64 individuals with ASD who came to our program from 2009 to 2014 for supported employment services as referred by the state vocational rehabilitation services agency. Employment specialists engaged in situational assessment, discovery, job development, customized job descriptions, on-site training and support, positive behavioral supports, and job retention techniques. The employment specialists were responsible for tracking their actual time spent working directly with or for the jobseeker with autism spectrum disorders (ASD). All vocational rehabilitation clients with ASD served during this time successfully secured CIE, and maintained their employment with ongoing supports, with intensity of support time decreasing over time. The majority (63/64, 98.4%) of individuals successfully secured CIE through the use of supported employment, in 72 unique employment positions. Of the majority of the individuals who secured employment, 77% (50) individuals indicated that they had never worked before and additional 18% (12) reported having short intermittent histories of employment. Despite this lack of employment experience, in all cases the jobseeker directed the job search and ultimately the job selection. PMID- 26855049 TI - Self-assembled ternary complexes stabilized with hyaluronic acid-green tea catechin conjugates for targeted gene delivery. AB - Nanosized polyelectrolyte complexes are attractive delivery vehicles for the transfer of therapeutic genes to diseased cells. Here we report the application of self-assembled ternary complexes constructed with plasmid DNA, branched polyethylenimine and hyaluronic acid-green tea catechin conjugates for targeted gene delivery. These conjugates not only stabilize plasmid DNA/polyethylenimine complexes via the strong DNA-binding affinity of green tea catechin, but also facilitate their transport into CD44-overexpressing cells via receptor-mediated endocytosis. The hydrodynamic size, surface charge and physical stability of the complexes are characterized. We demonstrate that the stabilized ternary complexes display enhanced resistance to nuclease attack and polyanion-induced dissociation. Moreover, the ternary complexes can efficiently transfect the difficult-to-transfect HCT-116 colon cancer cell line even in serum-supplemented media due to their enhanced stability and CD44-targeting ability. Confocal microscopic analysis demonstrates that the stabilized ternary complexes are able to promote the nuclear transport of plasmid DNA more effectively than binary complexes and hyaluronic acid-coated ternary complexes. The present study suggests that the ternary complexes stabilized with hyaluronic acid-green tea catechin conjugates can be widely utilized for CD44-targeted delivery of nucleic acid-based therapeutics. PMID- 26855051 TI - Evaluation of the effects of chemically different linkers on hepatic accumulations, cell tropism and gene silencing ability of cholesterol-conjugated antisense oligonucleotides. AB - Cholesterol conjugation of oligonucleotides is an attractive way to deliver the oligonucleotides specifically to the liver. However cholesterol-conjugated antisense oligonucleotides (ASOs) mainly accumulate in non-parenchymal cells (NPCs) such as Kupffer cells. In this study, to increase the hepatic accumulation of cholesterol-conjugated ASOs, we prepared a variety of linkers for cholesterol conjugation to anti-Pcsk9 ASOs and examined their effects on pharmacological parameters. Hepatic accumulation of ASO was dramatically increased with cholesterol conjugation. The increase in hepatic accumulation depended largely on the linker chemistry of each cholesterol-conjugated ASO. In addition to hepatic accumulation, the cell tropism of each cholesterol-conjugated ASO tended to depend on their linker. Although a linker bearing a disulfide bond accumulated mainly in NPCs, hexamethylene succinimide linker accumulated mainly in hepatocytes. To estimate the benefits of releasing ASO from the conjugated cholesterol in hepatocyte, we designed another linker based on hexamethylene succinimide, which has a phosphodiester bond between the linker and the ASO. The cholesterol-conjugated ASO bearing such a phosphodiester bond showed a significantly improved Pcsk9 mRNA inhibitory effect compared to its counterpart, cholesterol-conjugated ASO with a phosphorothioate bond, while the hepatic accumulation of both cholesterol-conjugated ASOs was comparable, indicating the effectiveness of removing the conjugated cholesterol for ASO activity. In toxicity analysis, some of the linkers induced lethal toxicities when they were injected at high concentrations (>600MUM). These toxicities were attributed to decreased platelet levels in the blood, suggesting an interaction between cholesterol-conjugated ASO and platelets. Our findings may provide a guideline for the design of molecule-conjugated ASOs. PMID- 26855050 TI - Tracking and quantifying polymer therapeutic distribution on a cellular level using 3D dSTORM. AB - We used a single-molecule localization technique called direct stochastic optical reconstruction microscopy (dSTORM) to quantify both colocalization and spatial distribution on a cellular level for two conceptually different N-(2 hydroxypropyl)methacrylamide (HPMA) copolymer conjugates. Microscopy images were acquired of entire cells with resolutions as high as 25nm revealing the nanoscale distribution of the fluorescently labeled therapeutic components. Drug-free macromolecular therapeutics consisting of two self-assembling nanoconjugates showed slight increase in nanoclusters on the cell surface with time. Additionally, dSTORM provided high resolution images of the nanoscale organization of the self-assembling conjugates at the interface between two cells. A conjugate designed for treating ovarian cancer showed that the model drug (Cy3) and polymer bound to Cy5 were colocalized at an early time point before the model drug was enzymatically cleaved from the polymer. Using spatial descriptive statistics it was found that the drug was randomly distributed after 24h while the polymer bound dye remained in clusters. Four different fluorescent dyes were used and two different therapeutic systems were tested to demonstrate the versatility and possible general applicability of dSTORM for use in studying drug delivery systems. PMID- 26855053 TI - Metal-conductive polymer hybrid nanostructures: preparation and electrical properties of palladium-polyimidazole nanowires. AB - A simple, convenient method for the formation of hybrid metal/conductive polymer nanostructures is described. Polyimidazole (PIm) has been templated on lambda-DNA via oxidative polymerisation of imidazole using FeCl3 to produce conductive PIm/DNA nanowires. The PIm/DNA nanowires were decorated with Pd (Pd/PIm/DNA) by electroless reduction of PdCl4(-2) with NaBH4 in the presence of PIm/DNA; the choice of imidazole was motivated by the potential Pd(II) binding site at the pyridinic N atom. The formation of PIm/DNA and the presence of metallic Pd on Pd/PIm/DNA nanowires were verified by FTIR, UV-vis and XPS spectroscopy techniques. AFM studies show that the nanowires have diameters in the range 5-45 nm with a slightly greater mean diameter (17.1 +/- 0.75 nm) for the Pd-decorated nanowires than the PIm/DNA nanowires (14.5 +/- 0.89 nm). After incubation for 24 h in the polymerisation solution, the PIm/DNA nanowires show a smooth, uniform morphology, which is retained after decoration with Pd. Using a combination of scanned conductance microscopy, conductive AFM and two-terminal measurements we show that both types of nanowire are conductive and that it is possible to discriminate different possible mechanisms of transport. The conductivity of the Pd/PIm/DNA nanowires, (0.1-1.4 S cm(-1)), is comparable to the PIm/DNA nanowires (0.37 +/- 0.029 S cm(-1)). In addition, the conductance of Pd/PIm/DNA nanowires exhibits Arrhenius behaviour (E(a )= 0.43 +/- 0.02 eV) as a function of temperature in contrast to simple Pd/DNA nanowires. These results indicate that although the Pd crystallites on Pd/PIm/DNA nanowires decorate the PIm polymer, the major current pathway is through the polymer rather than the Pd. PMID- 26855054 TI - Building a Dignified Identity: An Ethnographic Case Study of LGBT Catholics. AB - This ethnographic case study offers insight into religiously devout sexual minorities and the reasons behind their continued participation in an anti-gay religious institution, the Roman Catholic Church. I demonstrate how members of Dignity, an organization for gay, lesbian, bisexual, and transgender (LGBT) Catholics, strategically use their identity as gay Catholics to initiate action, to build community, and to destigmatize other religious sexual minorities. Members leverage this unique identity to push for change and equality within the Church. At the same time, this identity also allows members to see their continued participation in the anti-gay Roman Catholic Church as activism, a positive and affirming identity, thereby alleviating potential conflict and contradiction between their sexuality and their spirituality as Roman Catholics. PMID- 26855052 TI - Molecular engineering of high affinity single-chain antibody fragment for endothelial targeting of proteins and nanocarriers in rodents and humans. AB - Endothelial cells (EC) represent an important target for pharmacologic intervention, given their central role in a wide variety of human pathophysiologic processes. Studies in lab animal species have established that conjugation of drugs and carriers with antibodies directed to surface targets like the Platelet Endothelial Cell Adhesion Molecule-1 (PECAM-1, a highly expressed endothelial transmembrane protein) help to achieve specific therapeutic interventions in ECs. To translate such "vascular immunotargeting" to clinical practice, it is necessary to replace antibodies by advanced ligands that are more amenable to use in humans. We report the molecular design of a single chain variable antibody fragment (scFv) that binds with high affinity to human PECAM-1 and cross-reacts with its counterpart in rats and other animal species, allowing parallel testing in vivo and in human endothelial cells in microfluidic model. Site-specific modification of the scFv allows conjugation of protein cargo and liposomes, enabling their endothelial targeting in these models. This study provides a template for molecular engineering of ligands, enabling studies of drug targeting in animal species and subsequent use in humans. PMID- 26855055 TI - Effects of Dendritic Cell Subset Manipulation on Airway Allergy in a Mouse Model. AB - BACKGROUND: Two major distinct subsets of dendritic cells (DCs) are arranged to regulate immune responses: DEC-205+ DCs drive Th1 polarization and 33D1+ DCs establish Th2 dominancy. Th1 polarization can be achieved either by depletion of 33D1+ DCs with a 33D1-specific monoclonal antibody (mAb) or by activation of DEC 205+ DCs via intraperitoneal injection of alpha-galactosylceramide (alpha GalCer). We studied the effect of 33D1+ DC depletion or DEC-205+ DC activation in vivo using an established mouse model of allergic rhinitis (AR). METHODS: Mice were injected intraperitoneally with OVA plus alum and challenged 4 times with daily intranasal administration of OVA. Immediately after the last challenge, allergic symptoms such as sneezing and nasal rubbing as well as the number of cells in the bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF) were counted. The levels of serum OVA-specific IgG1, IgG2a, and IgE were also determined by ELISA. RESULTS: The allergic symptom scores were significantly decreased in 33D1+ DC-depleted or DEC-205+ DC-activated AR mice. The levels of OVA-specific IgG1, IgG2a, and IgE, and the number of NALF cells, but not BALF cells, were reduced in 33D1+ DC-depleted but not in DEC-205+ DC-activated AR mice. Moreover, the activated DEC-205+ DCs suppressed histamine release from IgE sensitized mast cells, probably through IL-12 secretion. CONCLUSIONS: The manipulation of innate DC subsets may provide a new therapeutic strategy for controlling various allergic diseases by reducing histamine release from IgE sensitized mast cells by driving the immune response towards Th1 dominancy via activation of DEC-205+ DCs in vivo. PMID- 26855056 TI - Neonatal severe hyperparathyroidism caused by homozygous mutation in CASR: A rare cause of life-threatening hypercalcemia. AB - Neonatal severe hyperparathyroidism (NSHPT) is a rare, life-threatening condition that presents with severe hypercalcemia, hyperparathyroidism, and osteopenia in the newborn period. Treatment of NSHPT traditionally includes hydration and bisphosphonates; however newer calcimimetic agents, such as cinacalcet, are now being utilized to prevent or delay parathyroidectomy which is technically difficult in the newborn. Medical treatment success is related to calcium sensing receptor (CaSR) genotype. We report a 4-day-old infant who presented with hyperbilirubinemia, poor feeding, weight loss, severe hypotonia and was ultimately diagnosed with NSHPT. The patient's total serum calcium level of 36.8 mg/dL (reference range: 8.5-10.4 mg/dL) is, to our knowledge, the highest ever documented in this setting. Exome data previously obtained on the infant's parents was re-analyzed demonstrating bi-parental heterozygosity for a mutation of the CASR gene: c.206G > A, and Sanger sequencing data confirmed the patient was a homozygote for the same mutation. Though a patient with the same CaSR gene mutation described here has responded to cinacalcet, our patient did not respond and required parathyroidectomy. Though this case has previously been published as a surgical case report, a full report of the medical management and underlying genetic etiology is warranted; this case underscores the importance of disclosing bi-parental heterozygosity for a gene causing severe neonatal disease particularly when treatment is available and illustrates the need for further in vitro studies of this CaSR mutation. PMID- 26855057 TI - Acute lymphoblastic leukemia in the context of RASopathies. AB - Noonan syndrome is associated with a range of malignancies including acute lymphoblastic leukemia (ALL). However, little information is available regarding the frequency, natural history, characteristics and prognosis of ALL in Noonan syndrome or RASopathies in general. Cross-referencing data from a large prospective cohort of 1176 patients having a molecularly confirmed RASopathy with data from the French childhood cancer registry allowed us to identify ALL in 6 (0.5%) patients including 4/778 (0.5%) with a germline PTPN11 mutation and 2/94 (2.1%) with a germline SOS1 mutation. None of the patients of our series with CFC syndrome (with germline BRAF or MAP2K1/MAP2K2 mutation - n = 121) or Costello syndrome (with HRAS mutation - n = 35) had an ALL. A total of 19 Noonan-ALL were gathered by adding our patients to those of the International Berlin-Munster Frankfurt (I-BFM) study group and previously reported patients. Strikingly, all Noonan-associated ALL were B-cell precursor ALL, and high hyperdiploidy with more than 50 chromosomes was found in the leukemia cells of 13/17 (76%) patients with available genetics data. Our data suggest that children with Noonan syndrome are at higher risk to develop ALL. Like what is observed for somatic PTPN11 mutations, NS is preferentially associated with the development of hyperdiploid ALL that will usually respond well to chemotherapy. However, Noonan syndrome patients seem to have a propensity to develop post therapy myelodysplasia that can eventually be fatal. Hence, one should be particularly cautious when treating these patients. PMID- 26855058 TI - Choroideremia research: Report and perspectives on the second international scientific symposium for choroideremia. AB - PURPOSE: To discuss progress in research on choroideremia (CHM) and related retinopathies with special emphasis on gene therapy approaches. METHODS: Biomedical and clinical researchers from across the world as well as representatives of the social science research community were convened to the 2nd International Scientific Symposium for Choroideremia in Denver, Colorado in June 2014 to enhance our understanding of CHM and accelerate the translation of research to clinical application for the benefit of those affected by CHM. RESULTS: Pre-clinical research using cell and animal models continues to further our understanding in the pathogenesis of CHM as well as to demonstrate proof-of concept for gene transfer strategies. With the advent of modern imaging technology, better outcome measures are being defined for upcoming clinical trials. Results from the first gene therapy trial in CHM show promise, with sustained visual improvement over 6 months post-treatment. Current and next generation gene transfer approaches may make targeted vector delivery possible in the future for CHM and other inherited retinal diseases. CONCLUSIONS: While no accepted therapies exist for CHM, promising approaches using viral-vectored gene therapy and cell therapies are entering clinical trials for eye diseases, with gene therapy trials underway for CHM. PMID- 26855059 TI - Regulation of connexins by the ubiquitin system: Implications for intercellular communication and cancer. AB - The connexins constitute a family of integral membrane proteins that form intercellular channels, enabling adjacent cells to directly exchange ions and small molecules. The connexin channels assemble into distinct plasma membrane domains known as gap junctions. Intercellular communication via gap junctions has an important role in regulating cell growth and differentiation, as well as in maintaining tissue homeostasis. Connexin43 (Cx43), the most ubiquitously expressed connexin isoform in human tissues, has been shown to act as a tumor suppressor and is frequently downregulated during cancer development. Cx43 has a short half-life, and modulation of the Cx43 turnover rate represents an important mechanism by which the level of gap junctional intercellular communication is regulated under basal conditions. Moreover, many growth factors, oncogenes, and tumor promoters are potent inducers of Cx43 endocytosis and endolysosomal degradation, resulting in loss of gap junctions. Emerging evidence indicates that the ubiquitin system has a major role in these processes. Recent studies have shown that ubiquitination is also involved in the autophagy-mediated degradation of Cx43 in a process mediated by the proto-oncogenic E3 ubiquitin ligase NEDD4. Moreover, ubiquitination of connexins has been implicated in modulating the level of intercellular communication via gap junctions in response to oxidative stress. This review article provides an overview of our current understanding of the role of the ubiquitin system in the regulation of connexins and discusses how the malfunction of these processes may contribute to the loss of intercellular communication via gap junctions during carcinogenesis. PMID- 26855060 TI - "It Was My Fault": Bullied Students' Causal and Controllable Attributions in Bullying Blogs. AB - Student bullying is a growing and damaging social problem. The devastating outcomes bullied individuals often experience due to such treatment make understanding this phenomenon imperative. Utilizing Heider's (1958) attribution theory, this study explores how bullied students (n = 100) attribute locus of causality and controllability for their victimization in 5 bullying blogs. Findings from this investigation reveal that (a) male and female bloggers' causal and controllable attributions do not differ; (b) bloggers most often attribute blame to bullies, although a noteworthy portion also attribute internal causation; and (c) bloggers often attribute bullying as uncontrollable for several reasons. This study also identifies factors that influence shifts in negative attributions about bullying. These findings inform bullying programs with the hope of reducing destructive attribution formations that potentially lead to prolonged victimization and detrimental consequences. PMID- 26855061 TI - Nutrient Insufficiencies/Deficiencies in Children With Sickle Cell Disease and Its Association With Increased Disease Severity. AB - BACKGROUND: Sickle cell disease (SCD) is characteristically described as a disease of hemolytic anemia and vaso-occlusive crises (VOCs). However, patients suffer from a multitude of other problems including impaired development, chronic pain, and increased susceptibility to infection. Nutritional deficiency has been implicated as a contributor to these issues. PROCEDURE: We reported the nutrition status with respect to vitamin D, zinc, B6, B12, folate, and homocysteine serum levels in Canadian children with SCD (n = 91). We also tested for associations between nutrients and markers of disease severity and growth. RESULTS: Almost half the sample (42%) had multiple nutrient insufficiencies/deficiencies, and a further 27% had a single insufficiency/deficiency. The most common insufficiency/deficiency was zinc in 57% followed by calcidiol (25 dihydroxyvitamin D (25(OH)D)) (52%). Sixteen percent of patients had low vitamin B6 levels, while folate, calcitriol (1,25(OH)D), and homocysteine levels were normal. Increased number of vitamin insufficiencies/deficiencies was associated with increasing disease severity (P = 0.018). Zinc insufficiency/deficiency was significantly associated with an increased number of home pain crises (P = 0.001) and an increased incidence of hospitalizations for VOCs (P = 0.01). CONCLUSIONS: Our findings show that patients with SCD commonly have multiple nutrient insufficiencies/deficiencies and support the growing evidence for the link between low zinc and increased VOC. It also indicates that increased nutrient insufficiencies/deficiencies are associated with increased disease severity in SCD. Prospective studies with larger samples are needed to further elucidate the relationship between nutrient deficiencies and SCD, and to determine whether nutrient supplementation can improve the disease course. PMID- 26855062 TI - Brain structure links everyday creativity to creative achievement. AB - Although creativity is commonly considered to be a cornerstone of human progress and vital to all realms of our lives, its neural basis remains elusive, partly due to the different tasks and measurement methods applied in research. In particular, the neural correlates of everyday creativity that can be experienced by everyone, to some extent, are still unexplored. The present study was designed to investigate the brain structure underlying individual differences in everyday creativity, as measured by the Creative Behavioral Inventory (CBI) (N=163). The results revealed that more creative activities were significantly and positively associated with larger gray matter volume (GMV) in the regional premotor cortex (PMC), which is a motor planning area involved in the creation and selection of novel actions and inhibition. In addition, the gray volume of the PMC had a significant positive relationship with creative achievement and Art scores, which supports the notion that training and practice may induce changes in brain structures. These results indicate that everyday creativity is linked to the PMC and that PMC volume can predict creative achievement, supporting the view that motor planning may play a crucial role in creative behavior. PMID- 26855063 TI - Low-cost and eco-friendly synthesis of silver nanoparticles using coconut (Cocos nucifera) oil cake extract and its antibacterial activity. AB - The present study reports the simple, inexpensive, eco-friendly synthesis of silver nanoparticles (AgNPs) using coconut oil cake extract. Scanning electron microscopy-energy dispersive spectroscopy peak at 3 keV confirmed the presence of silver. Transmission electron micrograph showed that nanoparticles are mostly circular with an average size of 10-70 nm. The results of the X-ray powder diffraction analysis (2theta = 46.2, 67.4 and 76.8) indicated the crystal nature of the AgNPs. Fourier transform infrared spectroscopy analysis indicates that proteins present in the oilcake extract could be responsible for the reduction of silver ions. The synthesized AgNPs (1-4 mm) reduced the growth rate of multi antibiotic-resistant bacteria such as Aeromonas sp., Acinetobacter sp. and Citrobacter sp. isolated from livestock wastewater. PMID- 26855064 TI - NMR Method for Characterizing Microsecond-to-Millisecond Chemical Exchanges Utilizing Differential Multiple-Quantum Relaxation in High Molecular Weight Proteins. AB - Chemical exchange processes of proteins on the order of microseconds (MUs) to milliseconds (ms) play critical roles in biological functions. Developments in methyl-transverse relaxation optimized spectroscopy (methyl-TROSY), which observes the slowly relaxing multiple quantum (MQ) coherences, have enabled the studies of biologically important large proteins. However, the analyses of MUs to ms chemical exchange processes based on the methyl-TROSY principle are still challenging, because the interpretation of the chemical exchange contributions to the MQ relaxation profiles is complicated, as significant chemical shift differences occur in both (1)H and (13)C nuclei. Here, we report a new methyl based NMR method for characterizing chemical exchanges, utilizing differential MQ relaxation rates and a heteronuclear double resonance pulse technique. The method enables quantitative evaluations of the chemical exchange processes, in which significant chemical shift differences exist in both the (1)H and (13)C nuclei. The versatility of the method is demonstrated with the application to KirBac1.1, with an apparent molecular mass of 200 kDa. PMID- 26855066 TI - Characterization and Generation of Local Occupied and Virtual Hartree-Fock Orbitals. AB - The scope of this review article is to discuss the locality of occupied and virtual orthogonal Hartree-Fock orbitals generated by localization function optimization. Locality is discussed from the stand that an orbital is local if it is confined to a small region in space. Focusing on locality measures that reflects the spatial extent of the bulk of an orbital and the thickness of orbital tails, we discuss, with numerical illustrations, how the locality may be reported for individual orbitals as well as for sets of orbitals. Traditional and more recent orbital localization functions are reviewed, and the locality measures are used to compare the locality of the orbitals generated by the different localization functions, both for occupied and virtual orbitals. Numerical illustrations are given also for large molecular systems and for cases where diffuse functions are included in the atomic orbital basis. In addition, we have included a discussion on the physical and mathematical limitations on orbital locality. PMID- 26855065 TI - Morphological and quantitative changes in mitochondria, plastids, and peroxisomes during the log-to-stationary transition of the growth phase in cultured tobacco BY-2 cells. AB - We developed a wide-range and high-resolution transmission electron microscope acquisition system and obtained giga-pixel images of tobacco BY-2 cells during the log and stationary phases of cell growth. We demonstrated that the distribution and ultrastructure of compartments involved in membrane traffic (i.e., Golgi apparatus, multivesicular body, and vesicle cluster) change during the log-to-stationary transition. Mitochondria, peroxisomes, and plastids were also enumerated. Electron densities of mitochondria and peroxisomes were altered during the growth-phase shift, while their numbers were reduced by nearly half. Plastid structure dramatically changed from atypical to spherical with starch granules. Nearly the same number of plastids was observed in both log and stationary phases. These results indicate that mechanisms regulating organelle populations differ from organelle to organelle. PMID- 26855067 TI - Blood pressure lowering and stroke events in type 2 diabetes: A network meta analysis of randomized controlled trials. PMID- 26855068 TI - An In Vitro Comparison of the Marginal Adaptation Accuracy of CAD/CAM Restorations Using Different Impression Systems. AB - PURPOSE: To compare the marginal adaptation of 3-unit zirconia fixed dental prostheses (FDPs) obtained from intraoral digital scanners (Lava True Definition, Cadent iTero), scanning of a conventional silicone impression, and the resulting master cast with an extraoral scanner (3Shape lab scanner). MATERIALS AND METHODS: One reference model was fabricated from intact, non-carious, unrestored human mandibular left first premolar and first molar teeth (teeth #19 and 21), prepared for a three-unit all-ceramic FDP. Impressions of the reference model were obtained using four impression systems (n = 10), group 1 (PVS impression scan), group 2 (stone cast scan), group 3 (Cadent iTero), and group 4 (Lava True Defintion). Then the three-unit zirconia FDPs were milled. Marginal adaptation of the zirconia FDPs was evaluated using an optical comparator at four points on each abutment. The mean (SD) was reported for each group. One-way ANOVA was used to assess the statistical significance of the results, with post hoc tests conducted via Tukey's HSD. p < 0.05 was considered statistically significant. All analyses were done using SPSS 22.0. RESULTS: The mean (SD) marginal gaps for the recorded data from highest to lowest were silicone impression scans 81.4 MUm (6.8), Cadent iTero scan 62.4 MUm (5.0), master cast scan 50.2 MUm (6.1), and Lava True definition scan 26.6 MUm (4.7). One-way ANOVA revealed significant differences (p < 0.001) in the mean marginal gap among the groups. The Tukey's HSD tests demonstrated that the differences between all groups (silicone impression scan, master cast scan, Lava True definition scan, iTero Cadent scan) were statistically significant (all p < 0.001). On the basis of the criterion of 120 MUm as the limit of clinical acceptance, all marginal discrepancy values of all groups were clinically acceptable. CONCLUSIONS: Within the confines of this in vitro study, it can be concluded that the marginal gap of all impression techniques was within the acceptable clinical limit (120 MUm). Group 4 (Lava True Defintion) showed the lowest average gap among all groups followed by group 2 (stone cast scan), group 3 (Cadent iTero), and group 1 (PVS impression scan); these differences were statistically significant. PMID- 26855069 TI - Characterization of 5alpha-reductase activity and isoenzymes in human abdominal adipose tissues. AB - INTRODUCTION: The substrate for the generation of 5alpha-dihydrotestosterone (DHT) is either androstenedione (4-dione) which is first converted to androstanedione and then to DHT through 17-oxoreductase activity, or testosterone, which is directly converted to DHT. Three 5alpha-reductase isoenzymes have been characterized and designated as types 1, 2 and 3 (SRD5A1, 2 and 3). OBJECTIVE: To define the predominant source of local DHT production in human adipose tissues, identify 5alpha-reductase isoenzymes and test their impact on preadipocyte differentiation. METHODS: Cultures of omental (OM) and subcutaneous (SC) preadipocytes were treated for 0, 6 or 24h with 30nM (14)C-4 dione or (14)C-testosterone, with and without 500nM 5alpha-reductase inhibitors 17-N,N-diethylcarbamoyl-4-methyl-4-aza-5-androstan-3-one (4-MA) or finasteride. Protein level and mRNA abundance of 5alpha-reductase isoenzymes/transcripts were examined in whole SC and OM adipose tissue. HEK-293 cells stably transfected with 5alpha-reductase type 1, 2 or 3 were used to test 5alpha-reductase inhibitors. We also assessed the impact of 5alpha-reductase inhibitors on preadipocyte differentiation. RESULTS: Over 24h, DHT formation from 4-dione increased gradually (p<0.05) and was significantly higher compared to that generated from testosterone (p<0.001). DHT formation from both 4-dione and testosterone was blocked by both 5alpha-reductase inhibitors. In whole adipose tissue from both fat compartments, SRD5A3 was the most highly expressed isoenzyme followed by SRD5A1 (p<0.001). SRD5A2 was not expressed. In HEK-293 cells, 4-MA and finasteride inhibited activity of 5alpha-reductases types 2 and 3 but not type 1. In preadipocyte cultures where differentiation was inhibited by 4-dione (p<0.05, n=7) or testosterone (p<0.05, n=5), the inhibitors 4-MA and finasteride abolished these effects. CONCLUSION: Although 4-dione is the main source of DHT in human preadipocytes, production of this steroid by 5alpha-reductase isoenzymes mediates the inhibitory effect of both 4-dione and testosterone on preadipocyte differentiation. PMID- 26855070 TI - The influence of vegetation and soil characteristics on active-layer thickness of permafrost soils in boreal forest. AB - Carbon release from thawing permafrost soils could significantly exacerbate global warming as the active-layer deepens, exposing more carbon to decay. Plant community and soil properties provide a major control on this by influencing the maximum depth of thaw each summer (active-layer thickness; ALT), but a quantitative understanding of the relative importance of plant and soil characteristics, and their interactions in determine ALTs, is currently lacking. To address this, we undertook an extensive survey of multiple vegetation and edaphic characteristics and ALTs across multiple plots in four field sites within boreal forest in the discontinuous permafrost zone (NWT, Canada). Our sites included mature black spruce, burned black spruce and paper birch, allowing us to determine vegetation and edaphic drivers that emerge as the most important and broadly applicable across these key vegetation and disturbance gradients, as well as providing insight into site-specific differences. Across sites, the most important vegetation characteristics limiting thaw (shallower ALTs) were tree leaf area index (LAI), moss layer thickness and understory LAI in that order. Thicker soil organic layers also reduced ALTs, though were less influential than moss thickness. Surface moisture (0-6 cm) promoted increased ALTs, whereas deeper soil moisture (11-16 cm) acted to modify the impact of the vegetation, in particular increasing the importance of understory or tree canopy shading in reducing thaw. These direct and indirect effects of moisture indicate that future changes in precipitation and evapotranspiration may have large influences on ALTs. Our work also suggests that forest fires cause greater ALTs by simultaneously decreasing multiple ecosystem characteristics which otherwise protect permafrost. Given that vegetation and edaphic characteristics have such clear and large influences on ALTs, our data provide a key benchmark against which to evaluate process models used to predict future impacts of climate warming on permafrost degradation and subsequent feedback to climate. PMID- 26855071 TI - 58 Years a Palliative Medicine Physician. PMID- 26855072 TI - Structure and Composition of the 200 K-Superconducting Phase of H2 S at Ultrahigh Pressure: The Perovskite (SH(-) )(H3 S(+) ). AB - At ultrahigh pressure (>110 GPa), H2 S is converted into a metallic phase that becomes superconducting with a record Tc of approximately 200 K. It has been proposed that the superconducting phase is body-centered cubic H3 S (Im3? m, a=3.089 A) resulting from the decomposition reaction 3 H2 S->2 H3 S+S. The analogy between H2 S and H2 O led us to a very different conclusion. The well known dissociation of water into H3 O(+) and OH(-) increases by orders of magnitude under pressure. H2 S is anticipated to behave similarly under pressure, with the dissociation process 2 H2 S->H3 S(+) +SH(-) leading to the perovskite structure (SH(-) )(H3 S(+) ). This phase consists of corner-sharing SH6 octahedra with SH(-) ions at each A site (the centers of the S8 cubes). DFT calculations show that the perovskite (SH(-) )(H3 S(+) ) is thermodynamically more stable than the Im3? m structure of H3 S, and suggest that the A site hydrogen atoms are most likely fluxional even at Tc . PMID- 26855073 TI - Case report of a large lactating adenoma with rapid antepartum enlargement. AB - INTRODUCTION: Lactating adenomas are rare benign breast tumors, most commonly found during pregnancy and lactation. They are usually slow growing and smaller than 3cm in maximal diameter. Rare cases of giant lactating adenomas and rapid postpartum enlargement have been reported, but none have shown a giant lactating adenoma with rapid antepartum enlargement or antepartum surgical management. CASE PRESENTATION: A 27 year-old pregnant woman presented at 28 weeks gestation with a 5cm left breast mass that doubled to 10cm within six weeks and was increasingly tender. Histopathologic examination of a core biopsy was consistent with a lactating adenoma. The mass was excised at 31 weeks gestation with no complications. DISCUSSION: Lactating adenomas are common during pregnancy and need to be distinguished from breast cancer, a commonly diagnosed malignancy in pregnancy. They can be distinguished from carcinoma and other benign tumors like fibroadenoma under histopathologic examination. Rare cases of giant lactating adenomas with rapid postpartum enlargement that were managed by postpartum excision have been reported. However, a giant lactating adenoma with rapid antepartum enlargement, managed by excision in the third trimester of pregnancy, has not been reported. CONCLUSION: Excision of a large, rapidly enlarging lactating adenoma in the third trimester of pregnancy is a safe and feasible management option. PMID- 26855074 TI - Abdominal wall herniae and their underlying pathology. AB - We describe a case of pseudomyxoma peritonei presenting as a strangulated inguinal hernia. We review the current literature regarding the incidence of underlying pathology in patients presenting with abdominal wall herniae and discuss the need for histological assessment of the hernia sac in selected patients. We highlight the importance of assessing for and being aware of significant underlying pathology in certain patients. PMID- 26855075 TI - Synovial chondromatosis of the right side temporomandibular joint extending to the middle cranial fossa: A case report with 7-year postoperative follow up and expression of a biomarker of cell proliferative activity. AB - INTRODUCTION: Synovial chondromatosis of the temporomandibular joint (TMJ) with cranial extension is rare. Here, we report 7-year follow-up of a case with immunohistochemical examination of cell proliferative activity. PRESENTATION OF CASE: The patient was a 72-year-old man. Severe bone resorption of the glenoid fossa was apparent on CT images. Pathological findings by biopsy led to diagnosis of synovial chondromatosis of the right side TMJ. Extirpation of the tumor was performed via temporopreauricular incision under general anesthesia. PCNA expression was examined by immunohistochemical analysis. The lesion had penetrated into the middle cranial fossa, but the cranial dura mater was intact. Expression of PCNA was confirmed. DISCUSSION: The PCNA expression suggested that growth activity caused expansion of the lesion to the skull base. CONCLUSION: We were able to follow up this case for a long period without recurrence postoperatively. PMID- 26855076 TI - Neurocognitive & neuropsychiatric phenotypes of PARK2-associated early-onset Parkinson's disease in two siblings. PMID- 26855077 TI - Second Language Experience Can Hinder the Discrimination of Nonnative Phonological Contrasts. AB - BACKGROUND/AIMS: Many studies have shown that experienced second language (L2) learners are more skilled than novice L2 learners at a variety of L2 tasks, including auditory discrimination between members of L2 phonological contrasts. In this paper we argued that while L2 experience is typically beneficial when comparing the effects of more versus less experience, it is not necessarily beneficial when comparing the effects of some experience versus none. METHODS: We compared the perceptual assimilation and discrimination of the Korean sibilant fricatives /s(h)/ and /s*/ by 3 native Mandarin populations: naive listeners, novice L2 learners (4-6 weeks of experience), and advanced L2 learners (over 2 years of experience). RESULTS: The perceptual assimilation of /s(h)/ changed as a result of L2 experience, but only in the /a/ context. It is also shown that novice L2 learners were less accurate than the naive listeners at discriminating between /s(h)/ and /s*/ but, crucially, only in the /a/ context. CONCLUSION: The perception of /s(h)/ by L2 learners may be affected by knowledge of the L2 unavailable to naive listeners, and some aspects of this knowledge may result in a decline in discrimination accuracy after even a very short period of L2 experience. PMID- 26855078 TI - Effects of synthetic conditions on the textural structure of pseudo-boehmite. AB - Mesoporous alumina with pseudo-boehmite phase was prepared by using the cation anion double hydrolysis method from mixed aqueous solution of aluminum sulfate and sodium aluminate. The effect of synthetic conditions on the crystal structure and textual properties of pseudo-boehmite was investigated, such as synthetic temperature, pH value and the addition of sodium silicate. With the assistance of characterization techniques, such as X-ray diffraction (XRD), N2 adsorption desorption isotherms (BET) and (27)Al magic-angle spinning nuclear magnetic resonance (MAS NMR), the relationship between textural properties of the mesoporous alumina samples and their synthetic conditions was discussed. The results displayed that an increase in synthesis temperature promoted the formation of higher crystalline pseudo-boehmite with the increase of its surface area and pore volume. Pure pseudo-boehmite phase could be obtained in the pH value range from 6.0 to 9.0, while bayerite phase occurred when the pH value was over 10.0. The introduction of sodium silicate could greatly improve the pore volume (1.20 cm(3)/g) and surface area (480.2 m(2)/g) of pseudo-boehmite. Interestingly, pure pseudo-boehmite phase was obtained at very high pH value without formation of bayerite phase when sodium silicate was initially added into the aluminum hydroxide colloid. PMID- 26855079 TI - Developmental Trajectories and Predictors of Prosocial Behavior Among Adolescents Exposed to the 2008 Wenchuan Earthquake. AB - This longitudinal study examined the developmental trajectories of prosocial behavior and related predictors among adolescents exposed to the 2008 Wenchuan earthquake. At 6-, 18-, and 30-months postearthquake, we followed a sample of 1,573 adolescents. Self-report measures were used to assess earthquake exposure, postearthquake negative life events, prosocial behavior, symptoms of posttraumatic stress disorder, depression, anxiety, social support, and coping style. Data were analyzed using growth mixture modeling and multinomial logistic regressions. Four trajectories of postearthquake prosocial behavior were identified in the sample: (a) high/enhancing (35.0%), (b) high/stable (29.4%), (c) low/declining (33.6%), and (d) low/steeply declining (2.0%). Female gender, more social support, and greater positive coping were significant factors related to a higher probability of developing the high/enhancing trajectory. These findings may be helpful for us to identify adolescents with poor prosocial behavior after exposure to earthquakes so as to provide them with appropriate intervention. PMID- 26855080 TI - G4 DNA in ras genes and its potential in cancer therapy. AB - It is now well established that in the human genome the canonical double helix coexists with folded G-quadruplex structures that are known to have important biological functions. In this review we summarize the current knowledge on quadruplex formation in the promoters of the ras genes that are mutated in about 30% of all human cancers. We describe the nuclear proteins that recognize these unusual DNA structures and discuss their function in transcription. We also examine the formation of G-quadruplexes in the 5'-untranslated region of the ras transcripts and conclude this review by reporting strategies that use either ras G-quadruplexes or proteins recognizing the ras G-quadruplexes as targets of anticancer small molecules. PMID- 26855081 TI - Microbiome, biofilms, and pneumonia in the ICU. AB - PURPOSE OF REVIEW: Lower respiratory tract infections remain one of the leading causes of death in the world. Recently, the introduction of molecular methods based on DNA sequencing and microarrays for the identification of nonculturable microorganisms and subspecies variations has challenged the previous 'one bug - one disease' paradigm, providing us with a broader view on human microbial communities and their role in the development of infectious diseases. The purpose of this review is to describe recent understanding of the role of microbiome and bacterial biofilm in the development of lung infections, and, at the same time, to present new areas of research opportunities. RECENT FINDINGS: The review describes recent literature in cystic fibrosis patients, chronic obstructive pulmonary disease patients, and literature in mechanically ventilated patients that helped to elucidate the role of microbiome and biofilm formation in the development of pneumonia. SUMMARY: The characterization of the human microbiome and biofilms has changed our understanding of lower respiratory tract infections. More comprehensive, sensitive, and fast methods for bacterial, fungal, and viral detection are warranted to establish the colonization of the lower respiratory tract in healthy individuals and sick patients. Future research might explore the global bacterial, fungal, and viral pulmonary ecosystems and their interdependence to target novel preventive approaches and therapeutic strategies in chronic and acute lung infections. PMID- 26855082 TI - Delivery of miR-200c Mimic with Poly(amido amine) CXCR4 Antagonists for Combined Inhibition of Cholangiocarcinoma Cell Invasiveness. AB - Cholangiocarcinoma is the second most common primary liver malignancy with extremely poor prognosis due to early invasion and widespread metastasis. The invasion and metastasis are regulated by multiple factors including CXCR4 chemokine receptor and multiple microRNAs. The goal of this study was to test the hypothesis that inhibition of CXCR4 combined with the action of miR-200c mimic will cooperatively enhance the inhibition of the invasion of human cholangiocarcinoma cells. The results show that CXCR4-inhibition polycation PCX can effectively deliver miR-200c mimic and that the combination treatment consisting of PCX and miR-200c results in cooperative antimigration activity, most likely by coupling the CXCR4 axis blockade with epithelial-to-mesenchymal transition inhibition in the cholangiocarcinoma cells. The ability of the combined PCX/miR-200c treatment to obstruct two migratory pathways represents a promising antimetastatic strategy in cholangiocarcinoma. PMID- 26855084 TI - Advances in the Application of Silicon and Germanium Nanowires for High Performance Lithium-Ion Batteries. AB - Li-alloying materials such as Si and Ge nanowires have emerged as the forerunners to replace the current, relatively low-capacity carbonaceous based Li-ion anodes. Since the initial report of binder-free nanowire electrodes, a vast body of research has been carried out in which the performance and cycle life has significantly progressed. The study of such electrodes has provided invaluable insights into the cycling behavior of Si and Ge, as the effects of repeated lithiation/delithiation on the material can be observed without interference from conductive additives or binders. Here, some of the key developments in this area are looked at, focusing on the problems encountered by Li-alloying electrodes in general (e.g., pulverization, loss of contact with current collector etc.) and how the study of nanowire electrodes has overcome these issues. Some key nanowire studies that have elucidated the consequences of the alloying/dealloying process on the morphology of Si and Ge are also considered, in particular looking at the impact that effects such as pore formation and lithium-assisted welding have on performance. Finally, the challenges for the practical implementation of nanowire anodes within the context of the current understanding of such systems are discussed. PMID- 26855083 TI - pCERC3 from a commensal ST95 Escherichia coli: A ColV virulence-multiresistance plasmid carrying a sul3-associated class 1 integron. AB - The rare sulphonamide resistance gene sul3 was found in the commensal Escherichia coli ST95 strain 22.1-R1 that was isolated in 2010 from the faeces of a healthy Australian adult. The genome of 22.1-R1 was sequenced and a 144,344bp RepFII/FIB plasmid, pCERC3, carrying sul3 was assembled. The sul3 gene is part of a class 1 integron featuring a sul3-containing conserved segment (sul3-CS) that replaced the classic sul1-containing 3'-conserved segment (3'-CS) usually seen in class 1 integrons. The integron contained the cassette array dfrA12-orfF-aadA2-cmlA1 aadA1-qacH, conferring resistance to trimethoprim, streptomycin, spectinomycin, chloramphenicol and quaternary ammonium compound. Two additional antibiotic resistance genes, blaTEM (ampicillin resistance) and tetA(B) (tetracycline) were adjacent to the integron, forming a single resistance region. In pCERC3, the sul3 type class 1 integron was flanked by sequence derived from the tnp and mer modules of Tn21 and was in the same location as In2, the sul1-containing In5-type class 1 integron of Tn21. At one end the sequence extends into Tn2670-derived sequence and then into sequence derived from the plasmid NR1 (R100). Examination of the sequences of eleven more complete sul3-containing plasmids in GenBank confirmed the relationship between sul3-associated integrons and Tn21/Tn2670/NR1. This suggests that the events that formed sul3-associated class 1 integrons occurred within the Tn21/Tn2670 context, most likely in NR1 or a related plasmid. The backbone of pCERC3 is most closely related to the backbones of ColV virulence plasmids and contains a complete ColV operon as well as several virulence associated genes and gene clusters. Hence, pCERC3 is both an antibiotic resistance and virulence plasmid. PMID- 26855085 TI - Crosslinking of Chitosan with Dialdehyde Derivatives of Nucleosides and Nucleotides. Mechanism and Comparison with Glutaraldehyde. AB - In medical and pharmaceutical applications, chitosan is used as a component of hydrogels-macromolecular networks swollen in water. Chemical hydrogels are formed by covalent links between the crosslinking reagents and amino functionalities of chitosan. To date, the most commonly used chitosan crosslinkers are dialdehydes, such as glutaraldehyde (GA). We have developed novel GA like crosslinkers with additional functional groups-dialdehyde derivatives of uridine (oUrd) and nucleotides (oUMP and oAMP)-leading to chitosan-based biomaterials with new properties. The process of chitosan crosslinking was investigated in details and compared to crosslinking with GA. The rates of crosslinking with oUMP, oAMP, and GA were essentially the same, though much higher than in the case of oUrd. The remarkable difference in the crosslinking properties of nucleoside and nucleotide dialdehydes can be clearly attributed to the presence of the phosphate group in nucleotides that participates in the gelation process through ionic interactions with the amino groups of chitosan. Using NMR spectroscopy, we have not observed the formation of aldimine bonds. It can be concluded that the real number of crosslinks needed to cause gelation of chitosan chains may be less than 1%. PMID- 26855086 TI - Direct ab Initio (Meta-)Surface-Hopping Dynamics. AB - Tractable methods for studying the molecular dynamics of chemical processes driven by electronic nonadiabaticity are highly sought after to provide insight into, for example, photochemical reaction mechanisms, molecular collisions, and thermalized electronic band structures. Starting from the time-dependent Schrodinger equation for a many-body system, a direct ab initio trajectory surface-hopping (TSH) method relying on an analytical treatment of nonadiabatic couplings between electronic states is developed in this work. An approach that combines time-dependent perturbation theory and explicit time evolution via TSH to expedite calculation of nonadiabatic transition rates, namely, meta-surface hopping dynamics, is presented, and an extrapolatory approach using time dependent perturbation theory for recovering unbiased transition rates is assessed. The meta-surface-hopping method is applied to the problem of estimating nonradiative relaxation rates of a photoexcited iminium ion, CH2NH2+, and evidence for internal consistency of the combined dynamics/perturbation theory approach is presented. PMID- 26855087 TI - Virotherapy of digestive tumors with rodent parvovirus: overview and perspectives. AB - INTRODUCTION: Toolan's H-1 parvovirus (H-1PV) exerts a cytotoxic/oncolytic effect, predominantly mediated by its non-structural protein (NS1). This rat parvovirus is harmless, unlike other parvoviruses, and its antitumor potential may be useful to clinicians as its oncolytic action appears to be true in numerous non-digestive and digestive cancers. AREAS COVERED: After a brief review of parvovirus genus and biology, we summarize the proposed mechanisms to explain the cytotoxicity of H-1PV to tumors which results in dysregulation of cell transcription, cell-cycle arrest, termination of cell replication, activation of cellular stress response and induction of cell death. Viral oncolysis induces a strong tumor-specific immune response leading to the recognition and elimination of minimal residual disease. As the action of H-1PV is not limited to the digestive tract, we initially analyse studies performed in non-digestive cancers such as glioma (as the virus is able to cross the blood brain barrier), and then focused more particularly on the results in digestive cancers. EXPERT OPINION: Based on the results of studies showing little H-1PV toxicity to living bodies, we advocate for the use of the parvovirus in cancers such as melanoma, glioma and pancreatic ductal adenocarcinoma in addition to conventional chemotherapy. PMID- 26855088 TI - Ag-Incorporated FHA Coating on Pure Mg: Degradation and in Vitro Antibacterial Properties. AB - Fluoridated hydroxyapatite (FHA) coating can help retard the degradation of magnesium, and possess good biocompatibility. However, the antibacterial property of FHA is very limited. In this work, we aimed to incorporate silver into FHA structure to fabricate biocompatible and antibacterial coatings with enhanced anticorrosion property. The results showed that the Ag-FHA coating prepared by electrochemical deposition and subsequent immersion in AgNO3 solution was superior to the Ag-FHA coating prepared by coelectrodeposition in terms of crystal structure, surface morphology and corrosion resistance. The release of Ag(+) ion causing high antiplanktonic bacterial rate and excellent antiadherence property to MRSA. Meanwhile, good cell compatibility of MC3T3-E1 including cell viability, cell adhesion, and cell morphology was achieved under the controlled degradation. The balance of degradation and antimicrobial property of Ag incorporated FHA coating made it an alternative in the application of surface modification for biodegradable Mg. PMID- 26855089 TI - Cervical Cancer Screening. AB - Recent changes in cervical cancer screening and management guidelines reflect our evolving knowledge about cervical carcinogenesis. In the pursuit of precision, however, decision-making has become complicated. We provide an overview of cervical cancer screening with a focus on what clinicians can do to maximize screening benefits while minimizing screening harms. The approach relies on categorizing women at each step in the screening process by their estimated risk of high-grade precancerous lesions and cervical cancer. Current screening guidelines are designed to find a reasonable balance between benefits and harms by recommending less screening in most women. Current management guidelines are designed to assure consistent decisions regarding referral to colposcopy. After initial colposcopy, we outline three major management options based on risk assessment. For treatment, we recommend ablational procedures when appropriate because they are similarly effective, less costly, and potentially safer than excisional procedures. We advise caution in adopting new screening strategies until they demonstrate cost-effective patient-centered improvements compared with current strategies. Clinicians can maximize their effect on cervical cancer prevention by being attentive to guidelines, assuring that women have access to appropriate human papillomavirus vaccination and providing low-cost, high-quality screening and treatment. PMID- 26855090 TI - Intimate Partner Sexual Assault: Traumatic Injuries, Psychological Symptoms, and Perceived Social Reactions. AB - OBJECTIVE: To compare the consequences of sexual assault based on the relationship of the woman to her named assailant. METHODS: From January 2008 to March 2011, we conducted an observational and prospective study of females older than age 15 years who were examined at a sexual assault referral center. Data were collected and comparisons made between groups based on the victim's relationship to her named assailant: a current or former intimate partner (grouped as intimate partner), stranger, or acquaintance. Data were collected regarding the patients, assailants, and type of assault. At a 1-month follow-up examination, we evaluated clinical findings and reported reactions by the victim's friends, family, and acquaintances. We conducted descriptive analyses and searched for overall and pairwise differences among groups. RESULTS: There were 797 individuals seen during this time period. Thirty of the victims were male and were excluded from the study, leaving 767 females older than 15 years of age, 294 (38%) of whom attended the follow-up consultation. Simultaneous physical and sexual assaults were more frequent in intimate partner assaults than in assaults by unknown individuals or acquaintances: 55% (95% confidence interval [CI] 49-61) compared with 31% (95% CI 26-36) and 32% (95% CI 26-38; P<.001). One month after the initial examination, psychological trauma was noted in 92% of the patients and was evenly distributed among the three groups. Reactions from family members were similar for victims assaulted by intimate partners and other victims. CONCLUSION: Sexual assault by an intimate partner is associated with higher rates of extragenital trauma and similar rates of psychologic trauma and disrupted other relationships as that associated with assaults by strangers or acquaintances. Sexual assaults by intimate partners should be viewed as serious as assault by other assailants by law enforcement, the judiciary, and the public. PMID- 26855091 TI - Risk of Occult Uterine Sarcoma in Women Undergoing Hysterectomy for Benign Indications. AB - OBJECTIVE: To estimate the frequency of unsuspected sarcoma identified postoperatively in women undergoing surgery for benign gynecologic indications at our institution. METHODS: Patients undergoing hysterectomy for benign gynecologic indications from 2000 to 2014 at our institution were identified. Patients who did not have a preoperative suspicion for malignancy and were found to have uterine sarcoma on pathology postoperatively were considered to have an occult uterine sarcoma. Relevant clinical and pathologic data were collected for this retrospective cohort study. RESULTS: A total of 10,119 hysterectomies for benign gynecologic indications were performed between 2000 and 2014. Among these, nine patients were found to have uterine sarcoma, with an overall rate 1 in 1,124 (95% confidence interval 1/592-1/2,457). These malignancies included five leiomyosarcomas, two endometrial stromal sarcomas, and two uterine adenosarcomas. Median age was 39 years (range 25-53 years). Among women found to have occult sarcoma, hysterectomy was performed as a primary indication for abnormal bleeding (77.8%) and leiomyomas (22.2%). Cases included six total abdominal hysterectomies, two total vaginal hysterectomies, and one supracervical hysterectomy. One case required manual morcellation during abdominal hysterectomy. Power morcellation was not used in any of the cases. CONCLUSION: In summary, occult uterine sarcoma occurs in 0.089% or 1 in 1,124 hysterectomies for benign indications in our population. The frequency is lower than the rate derived in earlier reports and by the U.S. Food and Drug Administration in their pooled analysis. PMID- 26855092 TI - Successful Oocyte Cryopreservation in Reproductive-Aged Cancer Survivors. AB - OBJECTIVE: To demonstrate that oocyte cryopreservation is a feasible reproductive option for patients with cancer of childbearing age who require gonadotoxic therapies. METHODS: This study is a university-based retrospective review of reproductive-aged cancer patient treatment cycles that included ovarian stimulation, transvaginal oocyte retrieval, oocyte cryopreservation, and, in some cases, subsequent oocyte thaw, in vitro fertilization, and embryo transfer. Outcome measures included ovarian stimulation response, number of oocytes retrieved, cryopreserved, and thawed, and pregnancy data. RESULTS: From 2005 to 2014, 176 reproductive-aged patients with cancer (median age 31 years, interquartile range 24-36) completed 182 oocyte cryopreservation cycles. Median time between consult request and oocyte retrieval was 12 days (interquartile range 10-14). Median peak stimulation estradiol was 1,446 pg/mL (interquartile range 730-2,687); 15 (interquartile range 9-23) oocytes were retrieved and 10 (interquartile range 5-18) metaphase II oocytes were cryopreserved per cycle. Ten patients (11 cycles) have returned to attempt pregnancy with their cryopreserved oocytes. Among thawed oocytes, the cryopreservation survival rate was 86% (confidence interval [CI] 78-94%). Nine of 11 thaw cycles resulted in embryos suitable for transfer. The embryo implantation rate was 27% (CI 8-46%) and the live birth rate was 44% (CI 12-77%) per embryo transfer. Chance for live birth with embryos created from cryopreserved oocytes was similar between the patients with cancer in this study and noncancer patients who underwent the same treatment at our center (44% [CI 12-77%] compared with 33% [CI 22-44%] per embryo transfer). CONCLUSION: Oocyte cryopreservation is now a feasible fertility preservation option for reproductive-aged patients with cancer who require gonadotoxic therapies. PMID- 26855093 TI - Chorioamnionitis and Neurocognitive Development at Age 2 Years. AB - OBJECTIVE: To evaluate whether chorioamnionitis is associated with decreased Bayley II scores at age 2 years. METHODS: We conducted an observational cohort study of women and their offspring enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Development's Maternal-Fetal Medicine Units Network multicenter, randomized controlled trial of magnesium for cerebral palsy prevention in pregnancies at high risk for early preterm delivery. We included nonanomalous singleton gestations and excluded pregnancies missing outcome or exposure data. Our primary exposure was chorioamnionitis, defined by the clinical diagnosis of chorioamnionitis and a maternal fever greater than 100 degrees F. Our primary outcome was a Bayley II Mental Developmental Index score less than 70 or Psychomotor Developmental Index score less than 70 assessed at age 2 years. We also assessed Mental Developmental Index or Psychomotor Developmental Index score less than 85. We conducted bivariate analyses and fit a log-linear regression model, adjusting for related to Mental Developmental Index or Psychomotor Developmental Index score less than 70 or less than 85 with a detectable effect size estimated at a relative risk of 1.5 or greater. RESULTS: Of 1,574 patients in our analysis, 194 (12%) had chorioamnionitis and 1,366 (87%) had preterm premature rupture of membranes. The mean gestational age at delivery was 29 3/7 weeks. There were no significant differences in Mental Developmental Index score less than 70 (37 [19.1%] compared with 233 [17%], P=.45) or Psychomotor Developmental Index score less than 70 (29 [15%] compared with 195 [14%] P=.76) for children born to mothers with or without chorioamnionitis, respectively. After adjusting for confounders, there remained no difference in the proportion of abnormal scores in either group. However, neonates diagnosed with sepsis were found to have significantly decreased Mental Developmental Index scores. CONCLUSION: Exposure to chorioamnionitis was not associated with neurocognitive defects as measured by abnormal Bayley II scores. PMID- 26855094 TI - Sexual Desire and Hormonal Contraception. AB - OBJECTIVE: To examine the effect of hormonal contraception on sexual desire. MATERIALS AND METHODS: We performed a cross-sectional analysis of 1,938 of the 9,256 participants enrolled in the Contraceptive CHOICE Project. This subset included participants enrolled between April and September 2011 who completed a baseline and 6-month telephone survey. Multivariable logistic regression was used to assess the association between contraceptive method and report of lacking interest in sex controlling for potential confounding variables. RESULTS: More than 1 in 5 participants (23.9%) reported lacking interest in sex at 6 months after initiating a new contraceptive method. Of 262 copper intrauterine device (IUD) users (referent group), 18.3% reported lacking interest in sex. Our primary outcome was more prevalent in women who were young (younger than 18 years: adjusted odds ratio [OR] 2.04), black (adjusted OR 1.78), and married or living with a partner (adjusted OR 1.82). Compared with copper IUD users, participants using depot medroxyprogesterone (adjusted OR 2.61, 95% confidence interval [CI] 1.47-4.61), the vaginal ring (adjusted OR 2.53, 95% CI 1.37-4.69), and the implant (adjusted OR 1.60, 95% CI 1.03-2.49) more commonly reported lack of interest in sex. We found no association between use of the hormonal IUD, oral contraceptive pill, and patch and lack of interest in sex. CONCLUSION: CHOICE participants using depot medroxyprogesterone acetate, the contraceptive ring, and implant were more likely to report a lack of interest in sex compared with copper IUD users. Future research should confirm these findings and their possible physiologic basis. Clinicians should be reassured that most women do not experience a reduced sex drive with the use of most contraceptive methods. PMID- 26855095 TI - Obstetric Anal Sphincter Injury as a Quality Metric: 16-Year Experience at a Single Institution. AB - OBJECTIVE: To evaluate trends in annual rates of vaginal birth, cesarean delivery, and obstetric anal sphincter injury at a single institution before and after the designation of obstetric anal sphincter injury as a measure of obstetric quality and safety. METHODS: This was a retrospective cohort study of women undergoing a singleton vaginal delivery and diagnosed with obstetric anal sphincter injury over a 16-year period. International Classification of Diseases, 9th Revision codes for perineal lacerations were used as identifiers. Trends in annual cesarean delivery, perineal laceration, and obstetric anal sphincter injury rates were assessed in a linear regression model. The data were divided into two time periods (1998-2005 and 2006-2013) based on the year (2006) in which obstetric anal sphincter injury was designated as a quality marker and compared. RESULTS: A total of 1,366 women had obstetric anal sphincter injury, and 1,360 were included for analysis. There was a 12.1% decline in annual vaginal delivery rates (from 77.1% to 67.8%) and a 40.6% increase in annual cesarean delivery rate (from 22.9% to 32.2%; P<.001). The rate of first-degree and second-degree laceration increased significantly (P=.009), and obstetric anal sphincter injury decreased significantly (P<.001). Operative vaginal birth and episiotomy were associated with obstetric anal sphincter injury in 2006-2013 compared with 1998 2005 (P<.001 and P=.018, respectively). CONCLUSION: After the designation of obstetric anal sphincter injury as an institutional quality measure, rates of obstetric anal sphincter injury decreased. PMID- 26855096 TI - Postpartum Hemorrhage and Use of Serotonin Reuptake Inhibitor Antidepressants in Pregnancy. AB - OBJECTIVE: To examine whether using selective serotonin reuptake inhibitors and selective serotonin-norepinephrine reuptake inhibitors in pregnancy is associated with an increased risk of postpartum hemorrhage. METHODS: We conducted a population-based cohort study including 225,973 women with 322,224 pregnancies in British Columbia, Canada, between 2002 and 2011. Women were categorized according to whether they had late-pregnancy exposure (at least 15 of the last 30 days of pregnancy), midpregnancy exposure (in the last 5 months of pregnancy but not the final 30 days), or no exposure. Postpartum hemorrhage was identified using International Classification of Diseases (9th and 10th Revisions) codes in data on all hospitalizations. RESULTS: We found an increased risk of postpartum hemorrhage associated with exposure to an serotonin-norepinephrine reuptake inhibitor in the final month of pregnancy after adjustment for potential confounders (n=1,390; adjusted odds ratio [OR] 1.76, 95% confidence interval [CI] 1.47-2.11, respectively) corresponding to 4.1 (95% CI 2.4-5.7) additional cases of postpartum hemorrhage per 100 people treated. There was no significant relationship between selective serotonin reuptake inhibitor use in the final month of pregnancy and postpartum hemorrhage (n=6,637; adjusted OR 1.09, 95% CI 0.98-1.21), except when confining the cohort to women with complete body mass index (BMI) information (n=235,031 [73%]) and controlling for BMI (adjusted OR 1.14, 95% CI 1.01-1.28) or when controlling for variables that are possibly on the causal pathway (adjusted OR 1.13, 95% CI 1.02-1.26). Midpregnancy exposure to a serotonin-norepinephrine reuptake inhibitor (n=242) or a selective serotonin reuptake inhibitor (n=1,507) was not associated with an increased postpartum hemorrhage risk. CONCLUSION: Serotonin-norepinephrine reuptake inhibitor exposure in late pregnancy was associated with a 1.6- to 1.9-fold increased risk of postpartum hemorrhage. PMID- 26855097 TI - Acupuncture to Reduce Sleep Disturbances in Perimenopausal and Postmenopausal Women: A Systematic Review and Meta-analysis. AB - OBJECTIVE: To examine the association of acupuncture with sleep disturbances and serum sex hormone levels in perimenopausal and postmenopausal women and whether there are associated changes in sex hormone levels. DATA SOURCES: We systematically searched electronic databases (EMBASE, PubMed, PsycINFO, CINAHL, ClinicalTrials.gov, Wanfang Data Chinese Database, and China Knowledge Resource Integrated Database) and the reference lists of the identified studies. METHODS OF STUDY SELECTION: Randomized controlled trials that examined the effects of acupuncture on sleep disturbances in perimenopausal and postmenopausal women were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement was followed. TABULATION, INTEGRATION, AND RESULTS: We identified 31 randomized controlled trials with 34 effect sizes involving a total of 2,433 participants. Acupuncture is associated with a significant reduction in the likelihood of sleep disturbances (odds ratio [OR] 0.21, 95% confidence interval [CI] 0.14-0.31), a significant increase in the secretion of serum estradiol (pooled difference in means 7.56 pg/mL, 95% CI 4.03-11.08), and reduction in the secretion of serum follicle-stimulating hormone (-6.75 milli-international units/mL, 95% CI -12.16 to -1.34) and luteinizing hormone (-2.71 milli international units/mL, 95% CI -4.22 to -1.20). Studies with a large effect size of acupuncture-associated changes in serum estradiol had a significantly lower odds of sleep disturbances than did those with a small-to-moderate effect sizes (ORs 0.07 and 0.36, P=.02). CONCLUSION: Acupuncture is associated with a significant reduction in sleep disturbances in women experiencing menopause related sleep disturbances. Our findings suggest that acupuncture should be adopted as part of a multimodal approach for improving sleep disturbances in perimenopausal and postmenopausal women. PMID- 26855100 TI - Modified Open Laparoscopy Using a 5-mm Laparoscope. AB - BACKGROUND: In an effort to minimize injuries associated with closed laparoscopic entry, many surgeons use a 10-mm standard open laparoscopy technique. Disadvantages of this open technique are that it requires a larger incision, fascial sutures, and does not always achieve an airtight seal. Although 5-mm laparoscopics with excellent optics are available, little has been written about open techniques using them. TECHNIQUE: We report a modified 5-mm open laparoscopy technique without fascial sutures. The fascia is elevated with small Kocher forceps and incised in the midline. The peritoneum is bluntly perforated with a hemostat-directed cephalad, and a blunt trocar with a sleeve is inserted in this direction. After rotating the sleeve toward the pelvis, a 5-mm laparoscope is placed into the abdomen before insufflation. EXPERIENCE: We have performed approximately 350 laparoscopies with only one major complication of a perforated transverse colon densely adherent beneath the umbilicus in a woman without previous abdominal surgery. Minor carbon dioxide leakage was uncommon and no wound infections or hernias occurred. CONCLUSION: This 5-mm modified open laparoscopic entry technique minimizes some of the disadvantages associated with conventional open and closed 10-mm laparoscopic techniques while avoiding blind placement of sharp instruments into the peritoneal cavity. PMID- 26855098 TI - Evaluation and Management of Women and Newborns With a Maternal Diagnosis of Chorioamnionitis: Summary of a Workshop. AB - In January 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development invited an expert panel to a workshop to address numerous knowledge gaps and to provide evidence-based guidelines for the diagnosis and management of pregnant women with what had been commonly called chorioamnionitis and the neonates born to these women. The panel noted that the term chorioamnionitis has been used to label a heterogeneous array of conditions characterized by infection and inflammation or both with a consequent great variation in clinical practice for mothers and their newborns. Therefore, the panel proposed to replace the term chorioamnionitis with a more general, descriptive term: "intrauterine inflammation or infection or both," abbreviated as "Triple I." The panel proposed a classification for Triple I and recommended approaches to evaluation and management of pregnant women and their newborns with a diagnosis of Triple I. It is particularly important to recognize that an isolated maternal fever is not synonymous with chorioamnionitis. A research agenda was proposed to further refine the definition and management of this complex group of conditions. This article provides a summary of the workshop presentations and discussions. PMID- 26855099 TI - Association of Cervical Effacement With the Rate of Cervical Change in Labor Among Nulliparous Women. AB - OBJECTIVE: To assess the association of cervical effacement with the rate of intrapartum cervical change among nulliparous women. METHODS: We conducted a secondary analysis of a prospective trial of intrapartum fetal pulse oximetry. For women who had vaginal deliveries, interval-censored regression was used to estimate the time to dilate at 1-cm intervals. For each given centimeter of progressive cervical dilation, women were divided into those who had achieved 100% cervical effacement and those who had not. The analysis was performed separately for women in spontaneous labor and those who were given oxytocin. RESULTS: A total of 3,902 women were included in this analysis, 1,466 (38%) who underwent labor induction, 1,948 (50%) who underwent labor augmentation (combined for the analysis), and 488 (13%) who labored spontaneously. For women in spontaneous labor, the time to dilate 1 cm was shorter for those who were 100% effaced starting at 4 cm of cervical dilation (P=.01 to <.001). For women who received oxytocin, the time to dilate 1 cm was shorter for those who were 100% effaced throughout labor (P<.001). CONCLUSION: The rate of cervical dilation among nulliparous women is associated with not only the degree of cervical dilation, but also with cervical effacement. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00098709. PMID- 26855102 TI - Placental Alpha-Microglobulin-1 Test in Resource-Limited Settings: A Cost Effectiveness Analysis. AB - OBJECTIVE: To evaluate whether the use of placental alpha-microglobulin-1 (PAMG 1) for the diagnosis of preterm premature rupture of membranes is cost-effective in resource-limited settings. METHODS: We designed a decision-analytic model from a third-party payer's perspective to determine the cost-effectiveness of the PAMG 1 test compared with the traditional diagnostic test of pooling, Nitrazine, and ferning in diagnosing preterm premature rupture of membranes in a resource limited setting. The primary health outcome of interest is the number of hospital transfers averted by each strategy per 1,000 patients screened. Baseline probabilities and cost assumptions were derived from published literature. We conducted sensitivity analyses using both deterministic and probabilistic models. Cost estimates reflect 2015 U.S. dollars. RESULTS: Under our baseline parameters, the use of a PAMG-1 test was the preferred cost-effective strategy. The PAMG-1 test averted hospital transfers of 447 true-negative patients per 1,000 tested at a cost of $143,407 ($320.82 per hospital transfer averted). The traditional test averted hospital transfers of 395 true-negative patients per 1,000 tested at a cost of $172,652 ($437.40 per hospital transfer averted). In a Monte Carlo simulation of 10 million trials, the PAMG-1 test was selected as the most cost effective strategy with a frequency of 74%. The traditional test was only selected with a frequency of 26%. The "do-nothing" strategy was not selected throughout the trial. CONCLUSION: Among women presenting at resource-limited settings with a history suspicious of preterm premature rupture of membranes between 24 and 36 weeks of gestation, our analysis provides evidence suggesting that PAMG-1 is the most cost-effective testing strategy. PMID- 26855101 TI - Measures of Maternal Stress and Mood in Relation to Preterm Birth. AB - OBJECTIVE: To investigate the relationships between psychological and physiologic measures of stress, mood, and gestational age at delivery and preterm birth. METHODS: This prospective cohort study recruited healthy women in the early second trimester who were 18-45 years of age. Validated psychological measures of perceived stress, depressive symptoms, and anxiety were completed at 16, 22, 28, 34, and 40 weeks of gestation. Cortisol concentration was measured in maternal hair at 16, 28, and 40 weeks of gestation to approximate first-, second-, and third-trimester levels of physiologic stress. Statistical methods included: analyses of variance, t tests, chi, Pearson correlations, regression modeling, and mediation analysis as appropriate. Hair cortisol concentrations were natural log-transformed to normalize values. RESULTS: Eleven (12%) of the 90 included women had a spontaneous preterm birth or preterm premature rupture of membranes. Perceived stress at 16 weeks of gestation correlated with both second-trimester cortisol concentration (r=0.28, P=.007) and earlier gestational age at delivery (r=-0.30, P<.01). Gestational age at delivery was also negatively correlated with cortisol concentration in the second trimester (r=-0.25, P=.02) and second trimester cortisol concentration was higher in preterm- (2.7 +/- 0.4 log transformed pg/mg) compared with term- (2.0 +/- 0.7 log-transformed pg/mg, P<.001) delivered women. Using mediation statistics, the association between the psychological measure, the physiologic measure, and gestational age at delivery was mainly driven by increased physiologic stress (hair cortisol concentration) in the second trimester (difference in coefficients [standard error]=-0.05 [0.02]). CONCLUSION: Higher perceived stress in the second trimester is associated with both elevated second-trimester hair cortisol concentration and gestational age at delivery. Physiologic measure of stress in the second trimester appears most strongly associated with preterm birth. Identification and amelioration of early pregnancy stressors may attenuate physiologic stress and ultimately affect preterm birth. PMID- 26855103 TI - Same-Day Discharge After Minimally Invasive Myomectomy. AB - OBJECTIVE: To estimate readmission rates of patients discharged home the same day after a minimally invasive myomectomy. METHODS: This is a retrospective case series of patients who underwent minimally invasive myomectomy and were discharged the same day, which examines the feasibility and safety by rates of readmission within Kaiser Permanente Northern California. Chart review was performed for outcomes of interest including readmission rates, emergency department, and urgent clinic visits within 48 hours, 7 days, and up to 3 months along with surgical and demographic characteristics. RESULTS: Of the 403 minimally invasive myomectomies performed during the study period, 88% (N=356) of patients were discharged home the same day. No readmissions required reoperation or were life-threatening. Two patients (0.6%) were readmitted within 48 hours for postoperative fever. A cumulative total of five patients (1.4%) were readmitted within 3 months. Urgent care and emergency department visits occurred in zero and seven patients (2.0%) within 48 hours of discharge, most commonly for pain and urinary retention. Median leiomyoma weight was 204 g, median body mass index was 26, median blood loss was 75 mL, and median surgical time was 157 minutes. CONCLUSION: Same-day discharge after minimally invasive myomectomy was found to have a low readmission rate and low health care utilization in the immediate postoperative period. Same-day discharge appears to be a safe option for healthy patients after undergoing an uncomplicated minimally invasive myomectomy. PMID- 26855104 TI - Trends in Periodic Surveillance Testing for Early-Stage Uterine Cancer Survivors. AB - OBJECTIVE: To examine the use of periodic surveillance testing for early-stage endometrial cancer survivors. METHODS: We performed a population-based analysis using the Surveillance, Epidemiology, and End Results-Medicare database, which was used to identify patients with stage I-II endometrioid endometrial cancer treated from 1992 to 2011. Three surveillance periods (7-18, 19-30, 31-42 months) after hysterectomy were examined. Use of vaginal cytology and imaging were quantified. RESULTS: We identified 17,638 patients. From 1992 to 2011, the use of chest radiography decreased (46.3-34.2%) during the first surveillance period, whereas imaging with chest computed tomography (CT) (0.9-12.6%), abdominopelvic CT (11.7-24.8%), and positron emission tomography (0-2.9%) increased (P<.001 for all). The use of cytology increased from 68.5% in 1992 to 72.3% in 2007 and then decreased to 66.9% in 2011 (P=.02). The mean number of cytologic samples obtained per patient increased from 1.3 in 1992 to 1.6 in 2008 and then declined to 1.3 in 2011, whereas the mean per patient number of chest CTs (0.02-0.2), abdominopelvic CTs (0.2-0.4), and positron emission tomographies (0-0.03) rose from 1992 to 2011. In 2011, 49.3% underwent radiologic surveillance 7-18 months after diagnosis, whereas 11.9% underwent two or more radiologic assessments in combination with cytology. These findings were similar for surveillance periods 2 and 3. CONCLUSION: The use of chest radiography has decreased and use of cytology has started to decline. However, the use of more costly imaging modalities is increasing despite a lack of evidence for the efficacy of these tests for early stage endometrial cancer survivors. PMID- 26855105 TI - Severe Maternal Morbidity and the Use of Assisted Reproductive Technology in Massachusetts. AB - OBJECTIVE: To assess whether risk of severe maternal morbidity at delivery differed for women who conceived using assisted reproductive technology (ART), those with indicators of subfertility but no ART ("subfertile"), and those who had neither ART nor subfertility ("fertile"). METHODS: This retrospective cohort study was part of the larger Massachusetts Outcomes Study of Assisted Reproductive Technology. To construct the Massachusetts Outcomes Study of Assisted Reproductive Technology database and identify ART deliveries, we linked ART treatment records to birth certificates and maternal and infant hospitalization records occurring in Massachusetts between 2004 and 2010. An algorithm of International Classification of Diseases, 9th Revision, Clinical Modification diagnosis and procedure codes identified severe maternal morbidity. We used logistic generalized estimating equations to estimate odds of severe maternal morbidity associated with fertility status, adjusting for maternal demographic and health factors and gestational age, stratifying on plurality and method of delivery. RESULTS: The prevalence of severe maternal morbidity among this population (n=458,918) was 1.16%. The overall, crude prevalences of severe maternal morbidity among fertile, subfertile, and ART deliveries were 1.09%, 1.44%, and 3.14%, respectively. The most common indicator of severe maternal morbidity was blood transfusion. In multivariable analyses, among singletons, ART was associated with increased odds of severe maternal morbidity compared with both fertile (vaginal: adjusted odds ratio [OR] 2.27, 95% confidence interval [CI] 1.78-2.88; cesarean: adjusted OR 1.67, 95% CI 1.40-1.98, respectively) and subfertile (vaginal: adjusted OR 1.97, 95% CI 1.30-3.00; cesarean: adjusted OR 1.75, 95% CI 1.30-2.35, respectively) deliveries. Among twins, only cesarean ART deliveries had significantly greater severe maternal morbidity compared with cesarean fertile deliveries (adjusted OR 1.48, 95% CI 1.14-1.93). CONCLUSION: Women who conceive through ART may have elevated risk of severe maternal morbidity at delivery, largely indicated by blood transfusion, even when compared with a subfertile population. Further research should elucidate mechanisms underlying this risk. PMID- 26855106 TI - Cervical Dilation on Admission in Term Spontaneous Labor and Maternal and Newborn Outcomes. AB - OBJECTIVE: To examine associations between cervical dilation on admission and maternal and newborn outcomes in term spontaneous labor. METHODS: This is a retrospective cohort study of 11,368 singleton, term (37-43 6/7 weeks of gestation) spontaneously laboring women delivering in 14 hospitals in Washington State between 2012 and 2014 using chart abstracted data from the Obstetrics Clinical Outcomes Assessment Program. Women with prior cesarean delivery or ruptured membranes on admission were excluded. Pregnancy history, cervical dilation on admission, and outcomes were analyzed. Associations between early (less than 4 cm cervical dilation) and late (4 cm or greater cervical dilation) admission and outcomes were examined using general linear models with a log-link stratifying by parity. Results were reported as adjusted relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Early admission compared with late admission was associated with increased epidural use of 84.8% compared with 71.8% in nulliparous women and 66.3% compared with 53.1% in multiparous women (nulliparous RR 1.18, 95% CI 1.13-1.24; multiparous RR 1.25, 95% CI 1.18-1.32); oxytocin augmentation in 58.5% compared with 36.6% in nulliparous women and 45.9% compared with 20.7% in multiparous women (nulliparous RR 1.56, 95% CI 1.50-1.63; multiparous RR 2.14, 95% CI 1.87-2.44); and cesarean delivery of 21.8% compared with 14.5% in nulliparous women and 3.7% compared with 1.9% in multiparous women (nulliparous RR 1.50, 95% CI 1.32-1.70; multiparous women RR 1.95, 95% CI 1.47 2.57). Early admission was associated with increased neonatal intensive care unit admission for newborns of nulliparous women only (RR 1.38, 95% CI 1.01-1.89). Between 2012 and 2014, late admission increased 14.6% for nulliparous patients and 10.1% for multiparous patients, and the cesarean delivery rate decreased from 10.5% to 7.9% (P<.001) for all. CONCLUSION: Early admission (less than 4 cm cervical dilation) is a risk factor for increased medical intervention and cesarean delivery. PMID- 26855107 TI - Association of Progestin Contraceptive Implant and Weight Gain. AB - OBJECTIVE: To evaluate initiation of a two-rod, 150-mg levonorgestrel contraceptive implant on women's perceived and observed body weight. METHODS: We conducted a secondary analysis of data from an open, randomized controlled trial of adult, nonpregnant, human immunodeficiency virus-negative women attending a public clinic in Kingston, Jamaica, who were assigned to initiate implant use either immediately or after a 3-month delay. The primary objective of the parent study was to assess the effect of initiation of the implant on the frequency of condom use. We compared study arms during follow-up using one-sided chi tests for differences in perceived weight gain and loss, one-sided Wilcoxon-Mann-Whitney tests for median gain in measured weight, and logistic regression with generalized estimating equations for risk of gaining greater than 2 kg. RESULTS: From 2012 to 2014, women were assigned to the implant (n=208) or delay arm (n=206). At 3 months, more women in the implant arm (15.3%) reported perceived weight gain than in the control arm (4.3%) (P=.01). Despite differences in perception, the implant and control arms did not differ significantly in median weight gain at 1-month (0.0 kg and 0.0 kg, respectively; P=.44) and 3-month visits (0.5 kg and 0.0 kg, respectively; P=.27). Study arms did not differ in risk of gaining greater than 2 kg (odds ratio 0.9, 95% confidence interval 0.6 1.3). CONCLUSION: We found no evidence of weight gain from short-term implant use. Through the power of the nocebo effect, the practice of counseling women to expect possible weight gain from initiating implant use could lead them to perceive weight gain even in its absence and contribute to the early discontinuation of this highly effective contraceptive method. PMID- 26855108 TI - Predictors of Failed Operative Vaginal Delivery in a Contemporary Obstetric Cohort. AB - OBJECTIVE: To identify factors associated with failed operative vaginal delivery in contemporary parturients and evaluate whether these factors can be used to accurately predict failed operative vaginal delivery. METHODS: This was a case control study of women undergoing a trial of operative vaginal delivery from a low or outlet station between 2005 and 2014. Women in the case group were defined as women who had an attempted operative vaginal delivery but ultimately required cesarean delivery. Women in the control group were defined as women who delivered vaginally. Bivariable and multivariable analyses were performed to determine factors that were independently associated with failed operative vaginal delivery. A receiver operating characteristic curve was created and area under the curve calculated to estimate the predictive capacity of these associations. RESULTS: Of 4,352 women who met inclusion criteria, 2,527 underwent an attempt at operative vaginal delivery using forceps and 1,825 using vacuum. Failure occurred in 272 (6.3%). In bivariable analysis, nulliparity, white race, induction of labor, chorioamnionitis, second stage 2 hours or greater, fetal occiput-posterior position, low station at application (compared with outlet), larger estimated fetal weight, and arrest or exhaustion as an indication for operative vaginal delivery (compared with a fetal indication) were significantly associated with a failed operative vaginal delivery. In multivariable analysis, factors that remained independently associated with operative vaginal delivery failure were race-ethnicity, arrest or exhaustion as an indication for operative vaginal delivery, occiput-posterior position, and a low pelvic application. The area under the curve for this regression was 0.74 (95% confidence interval 0.69-0.77) demonstrating less than optimal prediction of operative vaginal delivery failure. CONCLUSION: Risk factors identified before an operative vaginal delivery attempt cannot be used to accurately predict whether an operative vaginal delivery attempt will fail. PMID- 26855109 TI - Current Selection Criteria and Perioperative Therapy Used for Fetal Myelomeningocele Surgery. AB - OBJECTIVE: To determine the current maternal and fetal selection criteria and operative approaches used at centers performing fetal myelomeningocele surgery. METHODS: The 17 principal investigators participating in the Fetal Myelomeningocele Consortium were asked to participate in an anonymous online survey regarding the current practice of maternal-fetal surgery for neural tube defect repair and results were tabulated. The 35-question survey related to diagnostic testing, inclusion and exclusion criteria, and clinical management. RESULTS: Sixty-five percent (11/17) of principal investigators responded to the survey and not all centers responded to all 35 questions. All centers continue to use magnetic resonance imaging in their preoperative evaluation. Diagnostic testing from amniocentesis is varied: 5 of 11 (45%) require amniotic fluid alpha fetoprotein, 4 of 10 (40%) amniotic fluid acetylcholinesterase, and 8 of 11 (73%) DNA microarray. There is also variation from the Management of Myelomeningocele Study with regard to body mass index (BMI) (1/11; 9% would offer surgery with BMIs higher than 35), maternal medical risk factors (surgery would be offered for controlled pregestational diabetes [3/10 (30%)]), hepatitis C with negative viral load (4/11 [36%]), and human immunodeficiency virus with an undetectable viral load (1/10 [10%] or an obstetric history [3/11 (27%)] would offer surgery with a history of preterm delivery on progesterone). Ten of 11 (91%) centers did not consider ventriculomegaly of 18 mm and 9 of 11 (82%) centers did not consider lack of leg movement as an exclusion criteria. Nuances in the perioperative and intraoperative management were also reported, including 5 of 11 (45%) use intraoperative echocardiography and alterations in postoperative tocolytics. CONCLUSION: Variation in practice patterns for offering and performing maternal fetal surgery for myelomeningocele repair exists among centers. Ongoing evaluation of inclusion and exclusion criteria as well as operative techniques is warranted to ensure continued safety, effectiveness, and beneficence. PMID- 26855110 TI - Comparison of Women in Department Leadership in Obstetrics and Gynecology With Those in Other Specialties. AB - OBJECTIVE: To compare the representation of women in obstetrics and gynecology department-based leadership to other clinical specialties while accounting for proportions of women in historical residency cohorts. METHODS: This was a cross sectional observational study. The gender of department-based leaders (chair, vice chair, division director) and residency program directors was determined from websites of 950 academic departments of anesthesiology, diagnostic radiology, general surgery, internal medicine, neurology, obstetrics and gynecology, pathology, pediatrics, and psychiatry. Each specialty's representation ratio-proportion of leadership roles held by women in 2013 divided by proportion of residents in 1990 who were women-and 95% confidence interval (CI) were calculated. A ratio of 1 indicates proportionate representation. RESULTS: Women were significantly underrepresented among chairs for all specialties (ratios 0.60 or less, P<=.02) and division directors for all specialties except anesthesiology (ratio 1.13, 95% CI 0.87-1.46) and diagnostic radiology (ratio 0.97, 95% CI 0.81-1.16). The representation ratio for vice chair was below 1.0 for all specialties except anesthesiology; this finding reached statistical significance only for pathology, pediatrics, and psychiatry. Women were significantly overrepresented as residency program directors in general surgery, anesthesiology, obstetrics and gynecology, and pediatrics (ratios greater than 1.19, P<=.046). Obstetrics and gynecology and pediatrics had the highest proportions of residents in 1990 and department leaders in 2013 who were women. CONCLUSION: Despite having the largest proportion of leaders who were women, representation ratios demonstrate obstetrics and gynecology is behind other specialties in progression of women to departmental leadership. Women's overrepresentation as residency program directors raises concern because education-based academic tracks may not lead to major leadership roles. PMID- 26855111 TI - Use of Cefazolin for Group B Streptococci Prophylaxis in Women Reporting a Penicillin Allergy Without Anaphylaxis. AB - OBJECTIVE: To estimate the proportion of group B streptococci (GBS)-colonized women with a reported penicillin allergy without anaphylaxis receiving appropriate intrapartum antibiotic prophylaxis. METHODS: We performed a retrospective cohort study of GBS-colonized, penicillin-allergic women delivering at term receiving intrapartum antibiotic prophylaxis during labor. Scheduled cesarean deliveries were excluded. The primary outcome was the proportion of women who received appropriate antibiotic coverage, defined as penicillin or cefazolin. Secondary outcomes included neonatal outcomes such as Apgar score, blood draws, antibiotic use, length of hospital stay, and composite morbidity. RESULTS: Of 165 women reporting a penicillin allergy without anaphylaxis, 73 (44.2%) received an appropriate antibiotic and 92 (55.8%) received an inappropriate antibiotic. Of those receiving an inappropriate antibiotic, 56 (60.9%) were given clindamycin, 1 (1.1%) erythromycin, and 35 (38.0%) vancomycin. Women reporting rash as a penicillin reaction were more likely to receive cefazolin than another antibiotic (44 [60.3%] compared with 24 [26.1%], respectively; P<.001), whereas women whose reaction was not documented were less likely to receive cefazolin (18 [24.7%] compared with 63 [68.5%], respectively; P<.001). Among neonates whose mothers received appropriate compared with inappropriate antibiotics, there were no differences in Apgar score, number of blood draws, antibiotic use, length of hospital stay, or composite morbidity. CONCLUSION: More than half of women allergic to penicillin without anaphylaxis received an antibiotic other than penicillin or cefazolin as prophylaxis, indicating poor adherence to national guidelines. PMID- 26855112 TI - What Is New in Cervical Insufficiency? Best Articles From The Past Year. AB - This month we focus on current research in cervical insufficiency. Dr. Jackson discusses four recent publications, which are concluded with a "bottom line" that is the take-home message. The complete reference for each can be found in on this page, along with direct links to the abstracts. PMID- 26855113 TI - Lost in Translation: The Changing Language of Our Specialty. PMID- 26855115 TI - Modified endoscopic transnasal-transmaxillary-transpterygoid approach to parapharyngeal space tumor resection. AB - BACKGROUND: Conventional approaches for removing parapharyngeal space tumors require a cervical skin incision and resection of soft tissues between the skin and parapharyngeal space. The surgical visual field for this conventional approach is limited. METHODS: To decrease invasiveness during removal of benign parapharyngeal space tumors and to enhance the visual field, we devised a new approach called the modified endoscopic transnasal-transmaxillary-transpterygoid approach (MENMAP). The "surgical corridor" to the parapharyngeal space consists of the maxillary sinus, submucous tunnel under the lateral nasal wall, and the space created by removing the pterygoid process. RESULTS: We successfully performed en bloc removal of a parapharyngeal space tumor using the MENMAP approach. The only surgical complication was hypoesthesia of the right hard palate and maxillary gingiva, which gradually improved. CONCLUSION: The MENMAP approach is a viable alternative for removing parapharyngeal space tumors, as it is safe, feasible, and less invasive. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: 933-938, 2016. PMID- 26855116 TI - Mediating the Secondary Effects of Spinal Cord Injury Through Optimization of Key Physiologic Parameters. AB - Spinal cord injury remains a challenging clinical entity with considerable socioeconomic impact on patients, their families, and the healthcare system. Advances in medical care and rehabilitation continue to improve, but treatment outcomes following tissue regeneration for spinal cord injury remain dismal. Therefore, attempts at mediating the secondary effects of spinal cord injury remain the mainstay of current treatment. Recent studies evaluating the timing of decompression suggest improved neurologic recovery with early surgical decompression and the maintenance of mean arterial pressures >85 mm Hg. With systemic and local treatments, including riluzole, minocycline, GM1 ganglioside, BA-210, and granulocyte-colony stimulating factor, remaining in their infancy, randomized controlled trials demonstrating efficacy are needed before adopting their widespread use. PMID- 26855117 TI - Variability in Surgical Case Volume of Orthopaedic Surgery Residents: 2007 to 2013. AB - INTRODUCTION: Variability in orthopaedic surgery training is an important issue facing trainees. We examined orthopaedic surgery case logs for subspecialty case volume during residency training and assessed trends and variability in case volume over time. We hypothesized that there is variability in training in all subspecialties encountered in orthopaedic surgery resident training and that the volume of cases in each subspecialty has increased over time. METHODS: Annual surgical case logs of the Accreditation Council for Graduate Medical Education from 2007 to 2013 for orthopaedic surgery residency were assessed for variability and case volume trends. RESULTS: The average total adult cases logged per graduating resident in 2007 was 1,952, which increased to 2,291 in 2013, representing a 17.4% increase (P = 0.00041). The gap in case volume between residents in the 10th and 90th percentiles for case exposure decreased from 2007 to 2013 (P = 0.0268), although the 10th percentile group still logged significantly fewer procedures compared with the 90th percentile group in 2013 (P = 0.0159). CONCLUSIONS: Although case volume is not the sole determinant of surgical skill and further study is needed to investigate the effects of training experience, this variability in surgical volume may affect the knowledge, skill, and practice patterns of surgeons. PMID- 26855118 TI - Enhancing Drug Release From Antibiotic-loaded Bone Cement Using Porogens. AB - OBJECTIVE: To evaluate whether the addition of porogens to polymethyl methacrylate (PMMA) enhances the antibiotic elution rate from antibiotic-loaded bone cement. METHODS: Two porogens, gelatin sponge (Spongostan, Ferrosan Medical Devices) and ceramic granules (Bicera, Wiltrom), were added to liquid gentamicin loaded PMMA at increasing concentrations. Porosity was analyzed using Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy. Young's modulus and drug elution were also measured. The gentamicin content of the eluents was evaluated by o-phthaldialdehyde (OPA) assay on days 1, 2, 5, 7, 10, and 14. RESULTS: After day 5, the drug-releasing rate of Spongostan was significantly higher than that of Bicera in the order G3 > G2 > T3 > G1 > T2 > T1 > bone cement, where G represents the concentration of Spongostan and T represents the concentration of Bicera. The addition of Bicera and Spongostan increased the drug-releasing efficiency of PMMA by 3.75-fold and 5.65-fold, respectively. Spongostan also resulted in larger pores (ie, 70 to approximately 200 MUm) compared with Bicera (5 to 10 MUm) but reduced biomechanical strength. CONCLUSION: Both gelatin sponge and ceramic granules improved the local antibiotic elution rate, although the drug-releasing rate of Spongostan was significantly higher than that of Bicera. PMID- 26855119 TI - Complications and 30-day Outcomes Associated With Venous Thromboembolism in the Pediatric Orthopaedic Surgical Population. AB - INTRODUCTION: The risk of morbidity associated with venous thromboembolism (VTE) after pediatric orthopaedic surgery remains unclear despite increased use of thromboprophylaxis measures. METHODS: The American College of Surgeons National Surgical Quality Improvement Program, Pediatric database was queried for patients undergoing an orthopaedic surgical procedure between 2012 and 2013. Upper extremity and skin/subcutaneous surgeries were excluded. Associations between VTE and procedure, demographics, comorbidities, preoperative laboratory values, and 30-day postoperative outcomes were evaluated. RESULTS: Of 14,776 cases, 15 patients (0.10%) experienced postoperative VTE. Deep vein thrombosis (DVT) occurred in 13 patients (0.09%), and pulmonary embolism developed in 2 patients (0.01%). The procedure with the highest VTE rate was surgery for infection (1.2%). Patient factors associated with the development of VTE included hyponatremia (P = 0.003), abnormal partial thromboplastin time (P = 0.046), elevated aspartate transaminase level (P = 0.004), and gastrointestinal (P = 0.011), renal (P = 0.016), and hematologic (P = 0.019) disorders. Nearly half (46.2%) of DVTs occurred postdischarge. Complications associated with VTE included prolonged hospitalization (P < 0.001), pneumonia (P < 0.001), unplanned intubation (P = 0.003), urinary tract infection (P = 0.003), and central line associated bloodstream infection (P < 0.001). Most of the postoperative complications (66.7%) occurred before VTE diagnosis, and no patients with VTE died. CONCLUSION: In the absence of specified risk factors, thromboprophylaxis may be unnecessary for this population. PMID- 26855120 TI - Design and methods for the Better Resiliency Among Veterans and non-Veterans with Omega-3's (BRAVO) study: A double blind, placebo-controlled trial of omega-3 fatty acid supplementation among adult individuals at risk of suicide. AB - Suicide remains the 10th leading cause of death among adults in the United States (U.S.). Annually, approximately 30 per 100,000 U.S. military Veterans commit suicide, compared to 14 per 100,000 U.S. civilians. Symptoms associated with suicidality can be treatment resistant and proven-effective pharmaceuticals may have adverse side-effects. Thus, a critical need remains to identify effective approaches for building psychological resiliency in at-risk individuals. Omega-3 highly unsaturated fatty acids (n-3 HUFAs) are essential nutrients, which must be consumed in the diet. N-3 HUFAs have been demonstrated to reduce symptoms of depression, anxiety, and impulsivity - which are associated with suicide risk. Here we present the design and methods for the Better Resiliency Among Veterans and non-Veterans with Omega-3's (BRAVO) study, which is a double blind, randomized, controlled trial among individuals at risk of suicide of an n-3 HUFA versus placebo supplementation in the form of all natural fruit juice beverages. The BRAVO study seeks to determine if dietary supplementation with n-3 HUFAs reduces the risk for serious suicidal behaviors, suicidal thinking, negative emotions, and symptoms associated with suicide risk. Sub-analyses will evaluate efficacy in reducing depressive symptoms, alcohol, and nicotine use. A sub-study utilizes functional magnetic resonance imaging (fMRI) to evaluate the neuropsychological and neurophysiological effects of n-3 HUFAs. We also outline selection of appropriate proxy outcome measures for detecting response to treatment and collection of ancillary data, such as diet and substance use, that are critical for interpretation of results. PMID- 26855121 TI - Evaluating a small change approach to preventing long term weight gain in overweight and obese adults--Study rationale, design, and methods. AB - Despite the rapid rise in obesity worldwide, few strategies have been effective in treating this epidemic. An emerging strategy is to focus on preventing excessive weight gain rather than weight reduction. The proposed intervention, small change approach (SCA), is an innovative weight gain prevention strategy in which individuals monitor their usual nutrition and physical activity patterns and then make modest but sustainable alterations through behavioral intervention techniques (self-regulation, goal setting) enough to reduce overall energy balance by 100 to 200 kcal per day (e.g., reduce caloric intake by 100 kcal per day and/or increase daily step count by ~2000 steps (~100 kcal) per day). The primary aim of the trial is to determine whether small changes in energy expenditure and/or energy intake prevent weight gain in overweight and obese men and women long-term. The pre-specified primary and secondary assessments are at 2 and 3 years post-randomization respectively. The primary outcome is change in body weight. Secondary outcomes include body composition variables (adipose tissue distribution and lean mass distribution) and cardiorespiratory fitness (VO2peak). We randomized 320 primarily White (n=305) overweight and obese men and women to one of 2 conditions: 1) usual care (UC), 2) small change approach (SCA). Participant involvement in the study is 3 years; 2 year intervention with a 1 year follow-up. Our study findings will indicate whether there is value in clinicians adopting a SCA to lifestyle counseling for their patients who are overweight and obese. PMID- 26855122 TI - Four-port bimanual 23-gauge vitrectomy for diabetic tractional retinal detachment. AB - PURPOSE: Four-port bimanual vitrectomy is a surgical technique that facilitates removal of epiretinal membranes in severe proliferative diabetic retinopathy (PDR). As the illumination is held by the assistant through the fourth scleral incision, fibrovascular membranes are removed by bimanual manipulation techniques. The objective of this study was to evaluate the safety and efficacy of four-port bimanual 23-gauge vitrectomy for patients with tractional retinal detachment (TRD) in severe PDR. DESIGN: Retrospective, comparative, consecutive, interventional case series. METHODS: Sixty-six eyes of 58 consecutive patients who underwent primary vitrectomy for severe diabetic TRD. Thirty-six eyes of 31 cases that were treated with four-port 23-gauge vitrectomy were compared with 30 eyes of 27 cases that were treated with 23-gauge pars plana vitrectomy (PPV). Main outcome measures were best-corrected visual acuity (BCVA), retinal status, intraocular pressure, and incidence of intraoperative and postoperative complications with at least 6 months of follow-up. RESULTS: The primary and ultimate anatomic success rates (94.4% versus 93.3%, and 100% in both groups, respectively) and the mean BCVA changes did not differ significantly between groups. The whole surgical time and the membrane removal time were significantly (p < 0.001, respectively) shorter in the four-port 23-gauge group than in the 23 gauge group. There was no difference in the incidence of intraoperative and postoperative complications in both groups. CONCLUSIONS: Four-port bimanual 23 gauge vitrectomy offers comparable anatomic success and shortens the surgical time compared with conventional 23-gauge PPV in patients with TRD resulting from severe PDR. PMID- 26855123 TI - Study of RNA Polymerase II Clustering inside Live-Cell Nuclei Using Bayesian Nanoscopy. AB - Nanoscale spatiotemporal clustering of RNA polymerase II (Pol II) plays an important role in transcription regulation. However, dynamics of individual Pol II clusters in live-cell nuclei has not been measured directly, prohibiting in depth understanding of their working mechanisms. In this work, we studied the dynamics of Pol II clustering using Bayesian nanoscopy in live mammalian cell nuclei. With 50 nm spatial resolution and 4 s temporal resolution, Bayesian nanoscopy allows direct observation of the assembly and disassembly dynamics of individual Pol II clusters. The results not only provide quantifications of Pol II clusters but also shed light on the understanding of cluster formation and regulation. Our study suggests that transcription factories form on-demand and recruit Pol II molecules in their pre-elongation phase. The assembly and disassembly of individual Pol II clusters take place asynchronously. Overall, the methods developed herein are also applicable to studying a wide realm of real time nanometer-scale nuclear processes in live cells. PMID- 26855124 TI - alpha-Lipoic Acids Promote the Protein Synthesis of C2C12 Myotubes by the TLR2/PI3K Signaling Pathway. AB - Skeletal muscle protein turnover is regulated by endocrine hormones, nutrients, and inflammation. alpha-Lipoic acid (ALA) plays an important role in energy homeostasis. Therefore, the aim of this study was to investigate the effects of ALA on protein synthesis in skeletal muscles and reveal the underlying mechanism. ALA (25 MUM) significantly increased the protein synthesis and phosphorylation of Akt, mTOR, and S6 in C2C12 myotubes with attenuated phosphorylation of AMPK, Ikkalpha/beta, and eIF2alpha. Intraperitoneal injection of 50 mg/kg ALA also produced the same results in mouse gastrocnemius. Both the PI3K (LY294002) and mTOR (rapamycin) inhibitors abolished the effects of ALA on protein synthesis in the C2C12 myotubes. However, AICAR (AMPK agonist) failed to block the activation of mTOR and S6 by ALA. ALA increased TLR2 and MyD88 mRNA expression in the C2C12 myotubes. TLR2 knockdown by siRNA almost eliminated the effects of ALA on protein synthesis and the Akt/mTOR pathway in the C2C12 myotubes. Immunoprecipitation data showed that ALA enhanced the p85 subunit of PI3K binding to MyD88. These findings indicate that ALA induces protein synthesis and the PI3K/Akt signaling pathway by TLR2. PMID- 26855125 TI - Hydrogen Isotope Fractionation As a Tool to Identify Aerobic and Anaerobic PAH Biodegradation. AB - Aerobic and anaerobic polycyclic aromatic hydrocarbon (PAH) biodegradation was characterized by compound specific stable isotope analysis (CSIA) of the carbon and hydrogen isotope effects of the enzymatic reactions initiating specific degradation pathways, using naphthalene and 2-methylnaphtalene as model compounds. Aerobic activation of naphthalene and 2-methylnaphthalene by Pseudomonas putida NCIB 9816 and Pseudomonas fluorescens ATCC 17483 containing naphthalene dioxygenases was associated with moderate carbon isotope fractionation (epsilonC = -0.8 +/- 0.10/00 to -1.6 +/- 0.20/00). In contrast, anaerobic activation of naphthalene by a carboxylation-like mechanism by strain NaphS6 was linked to negligible carbon isotope fractionation (epsilonC = -0.2 +/- 0.20/00 to -0.4 +/- 0.30/00). Notably, anaerobic activation of naphthalene by strain NaphS6 exhibited a normal hydrogen isotope fractionation (epsilonH = -11 +/- 20/00 to -47 +/- 40/00), whereas an inverse hydrogen isotope fractionation was observed for the aerobic strains (epsilonH = +15 +/- 20/00 to +71 +/- 60/00). Additionally, isotope fractionation of NaphS6 was determined in an overlaying hydrophobic carrier phase, resulting in more reliable enrichment factors compared to immobilizing the PAHs on the bottle walls without carrier phase. The observed differences especially in hydrogen fractionation might be used to differentiate between aerobic and anaerobic naphthalene and 2-methylnaphthalene biodegradation pathways at PAH-contaminated field sites. PMID- 26855126 TI - Exposure characterization of three major insecticide lines in urine of young children in Japan-neonicotinoids, organophosphates, and pyrethroids. AB - The use of neonicotinoid (NEO) insecticides has increased over the past decade not only in Japan but also worldwide, while organophosphate (OP) and pyrethroid (PYR) insecticides are still conventionally used in agriculture and domestic pest control. However, limited data are currently available on the NEO exposure levels, especially in children, who are particularly vulnerable to environmental toxicants. Thus, the purpose of this study was to characterize the exposure to NEOs, as well as OPs and PYRs, in three-year-old Japanese children by assessing the range, distribution, and seasonal differences of the urinary concentrations of seven NEOs (acetamiprid, clothianidin, dinotefuran, thiacloprid, thiamethoxam, imidacloprid, and nitenpyram); four OP metabolites (dialkylphosphates [DAPs]), including dimethylphosphate, dimethylthiophosphate, diethylphosphate, and diethylthiophosphate; and three PYR metabolites (3-phenoxybenzoic acid, trans chrysanthemumdicarboxylic acid, and 3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylic acid). Urine samples were collected from 223 children (108 males and 115 females) in the summer and winter months. The detection rates of NEOs were 58% for dinotefuran, 25% for thiamethoxam, 21% for nitenpyram, and <16% for all other NEOs. The median and maximum concentrations of the sum of the seven NEOs (SigmaNEO) were 4.7 and 370.2nmol/g creatinine, respectively. Urinary SigmaNEO, dimethylphosphate, and all PYR metabolite concentrations were significantly higher in the summer than in the winter (p<0.05). The creatinine-adjusted concentration of SigmaNEO significantly correlated with those of all DAPs (p<0.05) but not with those of the PYR metabolites. Moreover, the NEO-detected group showed higher urinary SigmaDAP (sum of four OP metabolites) concentrations than the group without NEO detection. These findings suggest that children in Japan are environmentally exposed to the three major insecticide lines, and that the daily exposure sources of NEOs are common to those of OPs. PMID- 26855127 TI - Sheep lymph-nodes as a biological indicator of environmental exposure to fluoro edenite. AB - A significantly increased incidence of pleural mesothelioma in Biancavilla (Sicily, Italy) has been attributed to exposure to fluoro-edenite (FE), a fibrous amphibole extracted from a local stone quarry. The lymph-nodes draining the pulmonary lobes of sheep grazing around the town were examined, to gain insights into fibre diffusion. The pasture areas of six sheep flocks lying about 3km from Biancavilla were located using the global positioning system. The cranial tracheobronchial and one middle mediastinal lymph-node as well as four lung tissue samples were collected from 10 animals from each flock and from 10 control sheep for light and scanning electron microscopy (SEM) examination. The lymph nodes from exposed sheep were enlarged and exhibited signs of anthracosis. Histologically, especially at the paracortical level, they showed lymph-follicle hyperplasia with large reactive cores and several macrophages (coniophages) containing grey-brownish particulate interspersed with elements with a fibril structure, forming aggregates of varying dimensions (coniophage nodules). Similar findings were detected in some peribronchiolar areas of the lung parenchyma. SEM examination showed that FE fibres measured 8-41um in length and 0.4-1.39um in diameter in both lymph-nodes and lung tissue. Monitoring of FE fibres in sheep lymph-nodes using appropriate techniques can help set up environmental pollution surveillance. PMID- 26855128 TI - No association between soil constituents and amyotrophic lateral sclerosis relative risk in Ireland. AB - INTRODUCTION: We have recently mapped ALS spatial risk in Ireland using Bayesian and cluster analysis methods at electoral division (ED) and small area (SA) levels. As a number of metal elements (both minerals and toxins) have been proposed as risk factors for ALS, here we extend this analysis to include soil constituents from the Irish National Soils Database as Bayesian conditional auto regression covariates to determine associations with small area ALS risk. METHODS: Data on 45 different soil parameters were obtained under license from National Soils Database (via Irish EPA). We interpolated average values of each soil constituent for each small area using ordinary kriging. All cases of ALS in Ireland from January 1995 to December 2013 were identified from the Irish ALS register and observed and age and gender standardised expected cases were calculated for each SA. Besag-York-Mollie (BYM) models were then built including each parameter from the national soils database in turn as a Bayesian covariate in the BYM model. Models were compared using the deviance information criterion (DIC) and separate models were built for ALS subtypes. RESULTS: 1701 ALS patients were included - 959 (56%) were male, 938 (55%) had limb onset ALS. 315 Bayesian models were built in total. Of the 315 models built, only one resulted in a coefficient that did not overlap zero. For limb onset cases, total magnesium had a mean coefficient of 0.319 (credible interval 0.033-0.607). DISCUSSION: We report the first spatial analysis of potential association between ALS and soil minerals using a population-based dataset collected over 18 years. Our sole non zero finding is likely a random finding due to the high number of models built. We did not find any evidence to support soil mineral and toxin levels as risk factors for ALS. However as soil parameters are an ecological assessment of exposure in a given area, individual level measures of exposure are required. PMID- 26855130 TI - Correlates of resilience in the first 5 years after traumatic brain injury. AB - PURPOSE/OBJECTIVE: To examine resilience in the context of adjustment to traumatic brain injury (TBI), including the relative roles of demographic and theoretically related constructs such as coping, social support, and positive affectivity on resilience within the first 5 years postinjury. RESEARCH METHOD/DESIGN: This was a cross-sectional, observational study of 67 persons with medically documented mild complicated to severe TBI. Participants completed a battery of measures including cognitive tests; questionnaires assessing self report of emotional symptoms, perceived social support, and coping style; and a measure of resilience. RESULTS: Approximately 60% of the sample endorsed moderate to high levels of resilience during the first 5 years postinjury. Brain injury severity, premorbid intelligence, and cognitive flexibility did not predict resilience, as measured by the Connor-Davidson Resilience Scale. By contrast, task-oriented coping and perceived social support were strong and unique covariates of resilience. Positive and negative affectivity were related to resilience but were not unique covariates of it in the presence of task-oriented coping and perceived social support. Discriminant validity of resilience as a concept and the means of assessing it was supported by findings that emotion oriented and avoidance coping were not meaningfully related to resilience. CONCLUSIONS/IMPLICATIONS: Overall, the findings indicate that the majority of individuals in this sample reported high levels of resilience after brain injury and that correlates of resilience in adults with TBI is similar to that observed in adults without the history of cognitive impairment. (PsycINFO Database Record PMID- 26855129 TI - Spatio-temporal ozone variation in a case-crossover analysis of childhood asthma hospital visits in New York City. AB - BACKGROUND: Childhood asthma morbidity has been associated with short-term air pollution exposure. To date, most investigations have used time-series models, and it is not well understood how exposure misclassification arising from unmeasured spatial variation may impact epidemiological effect estimates. Here, we develop case-crossover models integrating temporal and spatial individual level exposure information, toward reducing exposure misclassification in estimating associations between air pollution and child asthma exacerbations in New York City (NYC). METHODS: Air pollution data included: (a) highly spatially resolved intra-urban concentration surfaces for ozone and co-pollutants (nitrogen dioxide and fine particulate matter) from the New York City Community Air Survey (NYCCAS), and (b) daily regulatory monitoring data. Case data included citywide hospital records for years 2005-2011 warm-season (June-August) asthma hospitalizations (n=2353) and Emergency Department (ED) visits (n=11,719) among children aged 5-17 years. Case residential locations were geocoded using a multi step process to maximize positional accuracy and precision in near-residence exposure estimates. We used conditional logistic regression to model associations between ozone and child asthma exacerbations for lag days 0-6, adjusting for co pollutant and temperature exposures. To evaluate the effect of increased exposure specificity through spatial air pollution information, we sequentially incorporated spatial variation into daily exposure estimates for ozone, temperature, and co-pollutants. RESULTS: Percent excess risk per 10ppb ozone exposure in spatio-temporal models were significant on lag days 1 through 5, ranging from 6.5 (95% CI: 0.2-13.1) to 13.0 (6.0-20.6) for inpatient hospitalizations, and from 2.9 (95% CI: 0.1-5.7) to 9.4 (6.3-12.7) for ED visits, with strongest associations consistently observed on lag day 2. Spatio-temporal excess risk estimates were consistently but not statistically significantly higher than temporal-only estimates on lag days 0-3. CONCLUSION: Incorporating case-level spatial exposure variation produced small, non-significant increases in excess risk estimates. Our modeling approach enables a refined understanding of potential measurement error in temporal-only versus spatio-temporal air pollution exposure assessments. As ozone generally varies over much larger spatial scales than that observed within NYC, further work is necessary to evaluate potential reductions in exposure misclassification for populations spanning wider geographic areas, and for other pollutants. PMID- 26855131 TI - The utility of tetraspanin CD9 as a biomarker for metastatic clear cell renal cell carcinoma. AB - The use of tetraspanin CD9 as a biomarker for renal cell carcinomas (RCC) has been explored with minor conclusions. Identification of a biomarker that not only distinguishes between the different types of renal cell carcinomas, but also predicts the metastatic potential of these tumors would significantly advance diagnosis and prognosis of kidney cancers. We utilized established cell lines to better understand the contribution of CD9 to the metastatic potential of clear cell renal cell carcinomas, and then applied our findings to the TCGA database and immunohistochemical analysis of human samples based on tumor grading to determine the utility of CD9 as a biomarker for RCC. Clear cell renal cell carcinoma (ccRCC) cell expression of tetraspanin CD9 was compared to normal kidney cells and found to be elevated. Upon knockdown of CD9, ccRCC cells obtained a more metastatic phenotype. We found E-cadherin expression to be repressed and the endothelial to mesenchymal transition markers Snail, Twist1, and Zeb1 to be elevated upon CD9 knockdown. Upon observing these gene expression changes in the TCGA database and in 10 cases, we found that CD9 and E-cadherin expression was lowered in higher grade ccRCC tumors. There was a significant correlation between CD9 and either E-cadherin, Snail, or Zeb1 in these tumors. Collectively, using tetraspanin CD9 in tandem with E-cadherin as a biomarker in renal cell carcinoma will help to not only distinguish between types, but also predict the metastatic potential of RCC. PMID- 26855132 TI - Role of miR-21 in alkalinity stress tolerance in tilapia. AB - MicroRNAs (miRNAs) are a class of short, evolutionary conserved non-coding RNA molecules, which are shown as the key regulators of many biological functions. External stress can alter miRNA expression levels, thereby changing the expression of mRNA target genes. Here, we show that miR-21 is involved in the regulation of alkalinity tolerance in Nile tilapia. Alkalinity stress results in a marked reduction in miR-21 levels. miR-21 loss of function could affect ion balance regulation, ROS production, and antioxidant enzyme activity in vivo. Moreover, miR-21 knockdown protects cell against alkalinity stress-induced injury in vitro. miR-21 directly regulates VEGFB and VEGFC expression by targeting the 3'-untranslated regions (UTRs) of their mRNAs, and inhibition of miR-21 significantly increases the levels of VEGFB and VEGFC expression in vivo. Taken together, our study reveals that miR-21 knockdown plays a protective role in alkalinity tolerance in tilapia. PMID- 26855134 TI - Homocysteine upregulates hepcidin expression through BMP6/SMAD signaling pathway in hepatocytes. AB - Subjects with severe hyperhomocysteinemia have hypoferric anemia and excessive iron deposition in the liver. Hepcidin, the central regulator of iron homeostasis, plays a key role in iron metabolism. However, the regulation of homocysteine (Hcy) on hepcidin is largely unclear. We conducted experiments in HepG2 cells to identify the mechanisms with which Hcy modulates hepcidin expression. We found that treatment with Hcy dose-dependently increased both hepcidin transcript levels and protein levels, as assessed by quantitative real time reverse-transcriptase polymerase chain reaction and western blotting, respectively. Hcy also activated BMP6 signaling and increased the phosphorylation of SMAD1/5/8 in HepG2 cells. We found that Hcy's effect on hepcidin expression was impaired by the knockdown of BMP6 and its receptors ALK2/3/6 with siRNAs. These results demonstrated that Hcy up-regulated hepcidin expression through the BMP6/SMAD pathway, suggesting a novel mechanism underlying the hyperhomocysteinemia-associated perturbation of iron homeostasis. PMID- 26855133 TI - Comparative analysis of gene expression in response to cold stress in diverse rice genotypes. AB - Cold stress is a major factor affecting rice (Oryza sativa) growth and productivity, limiting its distribution worldwide. Rice production is affected primarily due to its vulnerability to cold stress at seedling stage, as well as reproductive stage leading to spikelet sterility. We report here the analysis of 21 diverse rice genotypes from the USDA mini-core collection for cold tolerance and categorized their tolerance levels on the basis of reduction in growth measured by root and shoot length. The screening identified 12 cold tolerant genotypes from which six tolerant genotypes were characterized at the vegetative stage for cold tolerance and gas-exchange parameters. Two tolerant and two sensitive genotypes were used further for gene expression analysis. Lipid Transfer Protein (LTP) genes showed a clear difference in expression between cold tolerant and sensitive genotypes suggesting that they are good candidates for engineering cold tolerance in rice. Nipponbare was identified as a cold tolerant genotype with stress tolerance mechanism potentially operating via both ABA dependent and independent pathways. PMID- 26855135 TI - The small molecule survivin inhibitor YM155 may be an effective treatment modality for colon cancer through increasing apoptosis. AB - Survivin has a known beneficial role in the survival of both cancer cells and normal cells. Therapies targeting survivin have been proposed as an alternative treatment modality for various tumors; however, finding the proper indication for this toxic therapy is critical for reducing unavoidable side effects. We recently observed that high survivin expression in CD133(+) cells is related to chemoresistance in Caco-2 colon cancer cells. However, the effect of survivin targeted therapy on CD133(+) colon cancer is unknown. In this study, we investigated the roles of CD133 and survivin expression in colon cancer biology in vitro and comparatively analyzed the anticancer effects of survivin inhibitor on CD133(+) cells (ctrl-siRNA group) and small interfering RNA (siRNA)-induced CD133(-) cells (CD133-siRNA group) obtained from a single colon cancer cell line. CD133 knockdown via siRNA transfection did not change the tumorigenicity of cells, although in vitro survivin expression levels in CD133(+) cells were higher than those in siRNA-induced CD133(-) cells. The transfection procedure seemed to induce survivin expression. Notably, a significant number of CD133(-) cells (33.8%) was found in the cell colonies of the CD133-siRNA group. In the cell proliferation assay after treatment, YM155 and a combination of YM155 and 5 fluorouracil (5-FU) proved to be far more effective than 5-FU alone. A significantly increased level of apoptosis was observed with increasing doses of YM155 in all groups. However, significant differences in therapeutic effect and apoptosis among the mock, ctrl-siRNA, and CD133-siRNA groups were not detected. Survivin inhibitor is an effective treatment modality for colon cancer; however, the role of CD133 and the use of survivin expression as a biomarker for this targeted therapy must be verified. PMID- 26855136 TI - Global WASF-GA: An Evolutionary Algorithm in Multiobjective Optimization to Approximate the Whole Pareto Optimal Front. AB - In this article, we propose a new evolutionary algorithm for multiobjective optimization called Global WASF-GA ( global weighting achievement scalarizing function genetic algorithm), which falls within the aggregation-based evolutionary algorithms. The main purpose of Global WASF-GA is to approximate the whole Pareto optimal front. Its fitness function is defined by an achievement scalarizing function (ASF) based on the Tchebychev distance, in which two reference points are considered (both utopian and nadir objective vectors) and the weight vector used is taken from a set of weight vectors whose inverses are well-distributed. At each iteration, all individuals are classified into different fronts. Each front is formed by the solutions with the lowest values of the ASF for the different weight vectors in the set, using the utopian vector and the nadir vector as reference points simultaneously. Varying the weight vector in the ASF while considering the utopian and the nadir vectors at the same time enables the algorithm to obtain a final set of nondominated solutions that approximate the whole Pareto optimal front. We compared Global WASF-GA to MOEA/D (different versions) and NSGA-II in two-, three-, and five-objective problems. The computational results obtained permit us to conclude that Global WASF-GA gets better performance, regarding the hypervolume metric and the epsilon indicator, than the other two algorithms in many cases, especially in three- and five objective problems. PMID- 26855138 TI - Metabolite Profiling and Stable Isotope Tracing in Sorted Subpopulations of Mammalian Cells. AB - Biological samples such as tissues, blood, or tumors are often complex and harbor heterogeneous populations of cells. Separating out specific cell types or subpopulations from such complex mixtures to study their metabolic phenotypes is challenging because experimental procedures for separation may disturb the metabolic state of cells. To address this issue, we developed a method for analysis of cell subpopulations using stable isotope tracing and fluorescence activated cell sorting followed by liquid chromatography-high-resolution mass spectrometry. To ensure a faithful representation of cellular metabolism after cell sorting, we benchmarked sorted extraction against direct extraction. While peak areas differed markedly with lower signal for amino acids but higher signal for nucleotides, mass isotopomer distributions from sorted cells were generally in good agreement with those obtained from direct extractions, indicating that they reflect the true metabolic state of cells prior to sorting. In proof-of principle studies, our method revealed metabolic phenotypes specific to T cell subtypes, and also metabolic features of cells in the committed phase of the cell division cycle. Our approach enables studies of a wide range of adherent and suspension cell subpopulations, which we anticipate will be of broad importance in cell biology and biomedicine. PMID- 26855137 TI - The three-dimensional cancer genome. AB - The past decade of cancer research has ushered in a comprehensive understanding of the way that the sequence of the genome can be co-opted during the process of tumorigenesis. However, only recently has the epigenome, and in particular the three-dimensional topology of chromatin, been implicated in cancer progression. Here we review recent findings of how the cancer genome is regulated and dysregulated to effect changes in 3D genome topology. We discuss the impact of the spatial organization of the genome on the frequency of tumorigenic chromosomal translocations and the effects of disruption of the proteins responsible for the establishment of chromatin loops. Alteration of the three dimensional cancer genome is a rapidly emerging hallmark of multiple cancer subtypes. PMID- 26855139 TI - Drug usage patterns and treatment costs in newly-diagnosed type 2 diabetes mellitus cases, 2007 vs 2012: findings from a large US healthcare claims database analysis. AB - Objective To explore trends in demographics, comorbidities, anti-diabetic drug usage, and healthcare utilization costs in patients with newly-diagnosed type 2 diabetes mellitus (T2DM) using a large US claims database. Methods For the years 2007 and 2012, Truven Health Marketscan Research Databases were used to identify adults with newly-diagnosed T2DM and continuous 12-month enrollment with prescription benefits. Variables examined included patient demographics, comorbidities, inpatient utilization patterns, healthcare costs (inpatient and outpatient), drug costs, and diabetes drug claim patterns. Results Despite an increase in the overall database population between 2007-2012, the incidence of newly-diagnosed T2DM decreased from 1.1% (2007) to 0.65% (2012). Hyperlipidemia and hypertension were the most common comorbidities and increased in prevalence from 2007 to 2012. In 2007, 48.3% of newly-diagnosed T2DM patients had no claims for diabetes medications, compared with 36.2% of patients in 2012. The use of a single oral anti-diabetic drug (OAD) was the most common diabetes medication related claim (46.2% of patients in 2007; 56.7% of patients in 2012). Among OAD monotherapy users, metformin was the most commonly used and increased from 2007 (74.7% of OAD monotherapy users) to 2012 (90.8%). Decreases were observed for sulfonylureas (14.1% to 6.2%) and thiazolidinediones (7.3% to 0.6%). Insulin, predominantly basal insulin, was used by 3.9% of patients in 2007 and 5.3% of patients in 2012. Mean total annual healthcare costs increased from $13,744 in 2007 to $15,175 in 2012, driven largely by outpatient services, although costs in all individual categories of healthcare services (inpatient and outpatient) increased. Conversely, total drug costs per patient were lower in 2012 compared with 2007. Conclusions Despite a drop in the rate of newly-diagnosed T2DM from 2007 to 2012 in the US, increased total medical costs and comorbidities per individual patient suggest that the clinical and economic trends for T2DM are not declining. PMID- 26855140 TI - Pd-Catalyzed alpha-Selective C-H Functionalization of Olefins: En Route to 4 Imino-beta-Lactams. AB - Pd-catalyzed alpha-olefinic C-H activation of simple alpha,beta-unsaturated olefins has been developed. 4-imino-beta-lactam derivatives were readily synthesized via activation of alpha-olefinic C-H bonds with excellent cis stereoselectivity. A wide range of heterocycles at the beta-position are compatible with this reaction. The product of 4-imino-beta-lactam derivatives can be readily converted to 2-aminoquinoline which exists extensively in pharmaceutical drugs and natural products. PMID- 26855141 TI - Corrigendum: Multiple loss-of-function variants of taste receptors in modern humans. PMID- 26855142 TI - p16 Immunohistochemistry in Colposcope-Directed and Random Cervical Biopsies of CIN2 and CIN3. AB - OBJECTIVE: The aim of this study was to determine if there is a different p16 expression pattern between colposcope-directed and random (colposcope undetectable) biopsies of cervical intraepithelial neoplasia (CIN2) and CIN3. METHODS: Cervical biopsies that were positive for CIN2 or CIN3 were selected from a database of samples acquired during a large population-based clinical trial in Guangdong Province in China (Shenzhen Cervical Cancer Screening Study II). Blocks were recut, reread, and then immunostained for p16. Biopsies were categorized as either colposcope-directed or random biopsies. Diffuse staining was considered p16 positive, whereas focal or no staining was considered p16 negative. Differences were determined by the Fisher exact test. RESULTS: Among the patients with CIN3, there were 232 individual biopsies of CIN3. Sixty were randomly collected, and 172 were colposcopy directed. p16 positivity for the colposcope directed and random biopsies was 97.7% and 91.7%, respectively (p = 0.052). Like the CIN3 biopsies, colposcope-directed and random CIN2 samples expressed p16 similarly (86.8% [46/53] and 82.6% [19/23], p = .73, respectively). CONCLUSIONS: Based on our data, even small colposcope-undetectable biopsies of CIN3 are significant. Random biopsies of CIN2 or CIN3 demonstrate similar p16 positivity as visible lesions and therefore might be expected to have a similar natural history. PMID- 26855143 TI - Biomarkers p16, Human Papillomavirus and p53 Predict Recurrence and Survival in Early Stage Squamous Cell Carcinoma of the Vulva. AB - OBJECTIVE: Vulvar squamous cell carcinoma (VSCC) develops through 2 distinct molecular pathways, one involving high-risk human papillomavirus (HPV) infection and the other through early p53 suppressor gene mutation. We sought to evaluate the influence of p53 mutation, HPV status, and p16 expression on local recurrence and disease-specific mortality in early stage VSCC. MATERIALS AND METHODS: We performed a retrospective chart review of all patients with stage I VSCC at the Maine Medical Center from 1998 to 2007 (n = 92). Tumor size, depth of invasion, lymphatic/vascular space invasion, and growth pattern were recorded. Paraffin embedded tissue blocks were stained by immunohistochemistry for p16 and p53; high risk HPV was detected by polymerase chain reaction assay. Margin distance was determined by a gynecologic pathologist. Survival analyses were conducted to examine predictors of VSCC recurrence and disease-specific mortality. RESULTS: Age, depth of invasion, lymphatic/vascular space invasion, growth pattern, and margin status were not significant predictors of recurrence or disease-specific mortality. Tumor size of greater than 4.0 cm indicated a 4-fold increase in disease-specific mortality but did not significantly increase recurrence. p16 Positive patients were less likely to recur and had no VSCC-related deaths. Human papillomavirus-positive patients were less likely to recur and had no VSCC related deaths. p53-positive patients were 3 times more likely to recur and nearly 7 times more likely to die from vulvar cancer. CONCLUSIONS: Our findings suggest that HPV and the surrogate biomarker p16 indicate a less aggressive type of vulvar cancer. p53 positivity was associated with poor prognosis and significantly increased both recurrence and disease-specific mortality. PMID- 26855144 TI - High-Grade Cervical Intraepithelial Neoplasia Detected by Colposcopy-Directed or Random Biopsy Relative to Age, Cytology, Human Papillomavirus 16, and Lesion Size. AB - OBJECTIVE: The aim of the study was to determine whether p16 positive/cervical intraepithelial neoplasia (CIN) 2, 3, and cancer (p16 + CIN 2/3+) detected by colposcopy-directed or random biopsy differ by age, referral cytology, human papillomavirus (HPV) 16, and lesion size. MATERIALS AND METHODS: Data from the Shenzhen Cervical Cancer Screening Trial II where, at colposcopy, women who had directed and random cervical biopsies were reviewed to find women with CIN 2, 3, or cancer; 227 such women identified had their paraffin-embedded tissue blocks recut, reviewed, and then immune stained for p16. Data were analyzed by chi, Fisher exact test, and linear regression. RESULTS: After histopathologic review and p16 staining of CIN 2, 175 women were diagnosed with p16 + CIN 2/3+. When compared with those diagnosed by colposcopy-directed biopsy (n = 138), those diagnosed by random biopsy (n = 37) were more likely to have Cytology-Lo (cytology of negative, atypical squamous cells of undetermined significance, or low-grade squamous intraepithelial lesion; p = .07), less likely to have HPV 16 (p = .041), more likely to be 51 years or older (p = .022), and more likely to have 1 quadrant lesions (p < .001). Logistic regression analysis showed p16 + CIN 2/3+ diagnosed by random biopsy was predicted by 1 quadrant lesions (p < .0001) and age of 51 years or older (p = .03) but not by Cytology-Lo (p = .71) nor HPV 16 (p = .26). CONCLUSIONS: Women with p16 + CIN 2/3+ diagnosed by random biopsy are older and less likely to have HPV 16; hence, CIN diagnosed by random biopsy may not be as virulent as CIN diagnosed by colposcopy-directed biopsy. Regardless, we advise that CIN diagnosed by random biopsy be viewed like CIN diagnosed by colposcopy-directed biopsy. PMID- 26855145 TI - Performance of an Human Papillomavirus Test in Samples From Women With Histolopathologically Confirmed Invasive Cervical Cancer. AB - BACKGROUND: High-risk human papillomavirus (hrHPV) is now recognized as a single, necessary cause of cancer of the cervix. Although Pap tests have been central to cervical cancer screening programs for more than 50 years, tests that detect infection with these hrHPV genotypes are now being used increasingly in cervical cancer screening programs. OBJECTIVE: The aim of the study was to determine the sensitivity of an HPV test to detect cervical cancer. MATERIALS AND METHODS: Fifty successive cervical samples from women diagnosed with invasive cervical cancer were tested using a molecular HPV DNA test. Thereafter, the residual sample was further tested with a different HPV genotyping test (capable of detecting 27 low- and high-risk types of HPV) and a nucleic acid hybridization test (capable of detecting 13 high-risk types of HPV). RESULTS: Of the 50 women tested, the first HPV test was positive in 47 cases. Of the 3 negative cases, all were negative by second polymerase chain reaction-based test and 2 were negative by the nucleic acid hybridization test. Human immunodeficiency virus status was positive in 14 women, the majority of whom were positive for HPV 16 (n = 8) and 1 was HPV negative. Most women were diagnosed with having stage II cervical cancer or higher. CONCLUSIONS: With a sensitivity of 94% of the first HPV test, 6 of 100 cervical cancers will be missed if this was the only test used in a population screening program. The missed cancers were however all clinically detectable. PMID- 26855146 TI - p16 Staining of Cervical Biopsies May Decrease the Frequency of Unnecessary Loop Electrosurgical Excision Procedures. AB - OBJECTIVE: Loop electrosurgical excision procedures (LEEPs) are negative for high grade cervical intraepithelial neoplasia (CIN 2+) after a hematoxylin and eosin based CIN 2+ colposcopic biopsy diagnosis in 14% to 24% of cases. This may be due to diagnostic errors or biopsy-related regression of the dysplasia. Because p16 immunohistochemical staining of cervical biopsies improves diagnostic accuracy, we hypothesized that p16-based cervical biopsy diagnoses may reduce the frequency of negative LEEPs. MATERIALS AND METHODS: We performed a retrospective cross sectional study of all cervical LEEPs completed at our institution from 2002 to 2012. We recorded patient age, sexual history, smoking history, pathologic diagnoses (including whether the diagnosis was p16 based), the number of days from biopsy to follow-up LEEP, and clinical follow-up. This yielded 593 study subjects meeting inclusion criteria of CIN 2+ colposcopic diagnoses with follow up LEEP and 2 years of clinical follow-up. Colposcopic biopsies and follow-up LEEPs were reviewed and p16 immunostaining was performed on all samples to provide criterion standard results. Data were analyzed by chi and regression modeling. RESULTS: Our practice employed p16 to aid cervical biopsy diagnoses by 2006. The frequency of negative LEEPs before 2006 was 12 (10%) of 126. The frequency dropped during the p16 era (2006-2012) to 23 (5%) of 467. Overall, we observed an inverse relationship between the frequency of p16 employment and the frequency of negative LEEP outcomes (R = 0.71; p < .001), independent of potential covariates. CONCLUSIONS: Our data suggest that more accurate p16-based diagnoses may reduce the frequency of unnecessary LEEPs. PMID- 26855147 TI - Neuropeptide S modulates the amygdaloidal HCN activities (Ih) in rats: Implication in chronic pain. AB - Neuropeptide S (NPS), an endogenous anxiolytic, has been shown to protect against chronic pain through interacting with its cognate NPS receptor (NPSR) in the brain. However, the cellular mechanism of this NPS action remains unclear. We report that NPS inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channel current (Ih) in the rat's amygdala through activation of NPSR. This NPS effect is mediated through ERK1/2 phosphorylation in a subset of pyramidal like neurons located in the medial amygdala. The characters of the recorded Ih suggest a major role for HCN1 activity in this process. Inhibition of Ih by NPS stimulates the glutamatergic drive onto fast spiking intra-amygdalolidal GABAergic interneurons, which in turn facilitates GABA release onto pyramidal like neurons. Moreover, the HCN1 expression is increased in the amygdala of rats with peripheral nerve injury and intra-amygdaloidal administration of the HCN channel inhibitor ZD7288 attenuates nociceptive behavior in these rats. These results suggest that NPS-mediated modulation of intra-amygdaloidal HCN channel activities may be an important central inhibitory mechanism for regulation of chronic pain. PMID- 26855148 TI - Divergent clonal evolution of castration-resistant neuroendocrine prostate cancer. AB - An increasingly recognized resistance mechanism to androgen receptor (AR) directed therapy in prostate cancer involves epithelial plasticity, in which tumor cells demonstrate low to absent AR expression and often have neuroendocrine features. The etiology and molecular basis for this 'alternative' treatment resistant cell state remain incompletely understood. Here, by analyzing whole exome sequencing data of metastatic biopsies from patients, we observed substantial genomic overlap between castration-resistant tumors that were histologically characterized as prostate adenocarcinomas (CRPC-Adeno) and neuroendocrine prostate cancer (CRPC-NE); analysis of biopsy samples from the same individuals over time points to a model most consistent with divergent clonal evolution. Genome-wide DNA methylation analysis revealed marked epigenetic differences between CRPC-NE tumors and CRPC-Adeno, and also designated samples of CRPC-Adeno with clinical features of AR independence as CRPC-NE, suggesting that epigenetic modifiers may play a role in the induction and/or maintenance of this treatment-resistant state. This study supports the emergence of an alternative, 'AR-indifferent' cell state through divergent clonal evolution as a mechanism of treatment resistance in advanced prostate cancer. PMID- 26855149 TI - Combined inhibition of DDR1 and Notch signaling is a therapeutic strategy for KRAS-driven lung adenocarcinoma. AB - Patients with advanced Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant lung adenocarcinoma are currently treated with standard chemotherapy because of a lack of efficacious targeted therapies. We reasoned that the identification of mediators of Kras signaling in early mouse lung hyperplasias might bypass the difficulties that are imposed by intratumor heterogeneity in advanced tumors, and that it might unveil relevant therapeutic targets. Transcriptional profiling of Kras(G12V)-driven mouse hyperplasias revealed intertumor diversity with a subset that exhibited an aggressive transcriptional profile analogous to that of advanced human adenocarcinomas. The top-scoring gene in this profile encodes the tyrosine kinase receptor DDR1. The genetic and pharmacological inhibition of DDR1 blocked tumor initiation and tumor progression, respectively. The concomitant inhibition of both DDR1 and Notch signaling induced the regression of KRAS;TP53 mutant patient-derived lung xenografts (PDX) with a therapeutic efficacy that was at least comparable to that of standard chemotherapy. Our data indicate that the combined inhibition of DDR1 and Notch signaling could be an effective targeted therapy for patients with KRAS-mutant lung adenocarcinoma. PMID- 26855151 TI - A single-centre analysis of 30 patients with relapsed germ cell tumours treated with the TI-CE regimen. PMID- 26855150 TI - CYP3A5 mediates basal and acquired therapy resistance in different subtypes of pancreatic ductal adenocarcinoma. AB - Although subtypes of pancreatic ductal adenocarcinoma (PDAC) have been described, this malignancy is clinically still treated as a single disease. Here we present patient-derived models representing the full spectrum of previously identified quasi-mesenchymal (QM-PDA), classical and exocrine-like PDAC subtypes, and identify two markers--HNF1A and KRT81--that enable stratification of tumors into different subtypes by using immunohistochemistry. Individuals with tumors of these subtypes showed substantial differences in overall survival, and their tumors differed in drug sensitivity, with the exocrine-like subtype being resistant to tyrosine kinase inhibitors and paclitaxel. Cytochrome P450 3A5 (CYP3A5) metabolizes these compounds in tumors of the exocrine-like subtype, and pharmacological or short hairpin RNA (shRNA)-mediated CYP3A5 inhibition sensitizes tumor cells to these drugs. Whereas hepatocyte nuclear factor 4, alpha (HNF4A) controls basal expression of CYP3A5, drug-induced CYP3A5 upregulation is mediated by the nuclear receptor NR1I2. CYP3A5 also contributes to acquired drug resistance in QM-PDA and classical PDAC, and it is highly expressed in several additional malignancies. These findings designate CYP3A5 as a predictor of therapy response and as a tumor cell-autonomous detoxification mechanism that must be overcome to prevent drug resistance. PMID- 26855152 TI - Allogeneic hematopoietic cell transplantation as curative therapy for non transformed follicular lymphomas. AB - Allogeneic hematopoietic cell transplantation (HCT) offers the chance of cure for patients with non-transformed follicular lymphoma (FL), but is associated with the risk of non-relapse mortality (NRM). The aim of this study was to identify subgroups of FL patients who benefit from HCT. The European Society for Blood and Marrow Transplantation (EBMT) Minimum-Essential-A Data of 146 consecutive patients who received HCT for FL between 1998 and 2008 were extracted from the database of the German Registry 'DRST'. Diagnosis of FL was verified by contact with the reference pathologists. Estimated 1-, 2- and 5-year overall survivals (OS) were 67%, 60% and 53%, respectively. Day 100 NRM was 15%. Thirteen out of 33 patients (40%) with treatment-refractory disease (RD) at the time of transplantation survived long term. Univariate statistical analysis suggested limited chronic GvHD, donor age ?42 years and TBI-based conditioning in treatment refractory patients to correlate with favorable OS. Independent prognostic factors for OS were treatment-sensitive disease and limited chronic GvHD for the whole cohort, and additionally TBI-based conditioning for the treatment refractory subgroup. In contrast, patient age ?55 years had no impact on outcome. Thus, HCT for FL is associated with acceptable NRM, and offers a substantial chance of cure for patients with RD or advanced age. Donors ?42 years should be preferred if available. PMID- 26855153 TI - Pre-transplant diastolic but not systolic dysfunction has a negative prognostic impact after allogeneic stem cell transplantation. PMID- 26855154 TI - Prognostic relevance of pretransplant Deauville score on PET-CT and presence of EBV DNA in patients who underwent autologous stem cell transplantation for ENKTL. AB - High-dose chemotherapy and autologous stem cell transplantation (ASCT) for extranodal natural killer/T-cell lymphoma (ENKTL) is a reasonable option for a subset of patients. The impact of response status, according to positron emission tomography/computed tomography (PET/CT) results and/or presence of circulating EBV DNA prior to ASCT, has not yet been established. We analyzed 27 ENKTL patients with pre-ASCT circulating EBV DNA who had undergone pre-ASCT PET/CT between 2009 and 2014. We classified patients into two groups based on the result of pretransplantation assessment: a favorable risk group (pretransplant five point Deauville score (DS) of 1-2 based on PET/CT and no detectable EBV DNA) and an unfavorable risk group (DS 1-2 with detectable EBV DNA, DS 3-5 with or without detectable EBV DNA). After a median follow-up of 37 months, overall survival and PFS were significantly different between the two groups (median OS: not reached for favorable risk group vs 7.0 months for unfavorable risk group, P=0.017; median PFS: 16.0 vs 5.0 months, P=0.019). Multivariate analysis revealed that pre ASCT DS and EBV DNA was the only independent prognostic factor considering stage, IPI and NKPI. Precise assessment of the status of disease before transplantation may provide more benefit from ASCT to ENKTL patients. PMID- 26855156 TI - Excellent outcome with a high proportion of mixed chimerism in patients with severe aplastic anemia treated with partially T-cell-depleted peripheral hematopoietic stem cell transplants. PMID- 26855155 TI - Acute kidney injury in HCT: an update. AB - Acute kidney injury (AKI) is highly prevalent whether the patients undergo myeloablative or non-myeloablative hematopoietic cell transplantation (HCT); however, the pathogenesis and risk factors leading to AKI can differ between the two. The prognosis of AKI in patients receiving HCT is poor. In fact, AKI following HCT is associated not only with increased short- and long-term mortality, but also with progression to chronic kidney disease. Herein, the authors provide a comprehensive and up-to-date review of the definition and diagnosis, as well as of the incidence, pathogenesis and outcome of AKI in patients undergoing HCT, centering on the differences between myeloablative and non-myeloablative regimens. PMID- 26855157 TI - Shortened apheresis-based extra-corporeal photochemotherapy for acute refractory GVHD in children: a prospective study. PMID- 26855161 TI - Identity formation and motivation of new faculty developers: A replication study in a resource constrained university. AB - INTRODUCTION: Previous studies on the identity development and motivation of faculty developers have occurred with seasoned developers in a research-rich environment. We sought to determine if the findings of those studies could be replicated with novice faculty developers in a resource-constrained environment. METHODS: We interviewed 15 novice faculty developers from Muhimbili University of Health and Allied Sciences (MUHAS) who, at the time, had led faculty development activities for no more than two years. We conducted a qualitative analysis sensitized by the previous findings. RESULTS: Results were very similar to the previous work. The developers described compartmentalized, hierarchical, and merged identities. The impact was on their teaching as well as on others at MUHAS and on the institution itself. The motivations related to mastery, purpose, duty, satisfaction, and relatedness. CONCLUSION: This replication led us to conclude that identity development as a faculty developer occurs even in novice developers who do faculty development as only part of their work and despite constrained resources and a different culture. These developers find the work richly rewarding and their motivations benefit the institution. This body of research highlights how faculty development provides benefits to the institution as well as engaging career opportunities. PMID- 26855158 TI - Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI. AB - Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already been published. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006-2012). Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the French Society for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading to a low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignant diseases remained significant risk factors (P=0.04 and P<0.0001, respectively). In multivariate analysis, only status of disease was a significant risk factor (P<0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/or HLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their role was more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio=0.57 [0.32-1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort. PMID- 26855162 TI - Chemical Bath Deposition of p-Type Transparent, Highly Conducting (CuS)x:(ZnS)1-x Nanocomposite Thin Films and Fabrication of Si Heterojunction Solar Cells. AB - P-type transparent conducting films of nanocrystalline (CuS)x:(ZnS)1-x were synthesized by facile and low-cost chemical bath deposition. Wide angle X-ray scattering (WAXS) and high resolution transmission electron microscopy (HRTEM) were used to evaluate the nanocomposite structure, which consists of sub-5 nm crystallites of sphalerite ZnS and covellite CuS. Film transparency can be controlled by tuning the size of the nanocrystallites, which is achieved by adjusting the concentration of the complexing agent during growth; optimal films have optical transmission above 70% in the visible range of the spectrum. The hole conductivity increases with the fraction of the covellite phase and can be as high as 1000 S cm(-1), which is higher than most reported p-type transparent materials and approaches that of n-type transparent materials such as indium tin oxide (ITO) and aluminum doped zinc oxide (AZO) synthesized at a similar temperature. Heterojunction p-(CuS)x:(ZnS)1-x/n-Si solar cells were fabricated with the nanocomposite film serving as a hole-selective contact. Under 1 sun illumination, an open circuit voltage of 535 mV was observed. This value compares favorably to other emerging heterojunction Si solar cells which use a low temperature process to fabricate the contact, such as single-walled carbon nanotube/Si (370-530 mV) and graphene/Si (360-552 mV). PMID- 26855163 TI - Effect of sex and time to slaughter (transportation and lairage duration) on the levels of cortisol, creatine kinase and subsequent relationship with pork quality. AB - The study determined the effect of sex and time to slaughter on cortisol and creatine kinase levels, and pork quality in commercial crossbred pigs. Saliva samples were before collected transportation, on arrival at the abattoir, and after a 20 hour lairage period. Cortisol levels from saliva (SC), serum (SeC) and urine (UC) were determined. Creatine kinase (CK) levels were determined from serum samples. Fifteen boars vs. 15 gilts were immediately slaughtered on arrival (SOA), and the other 15 boars vs. 15 gilts were rested for 20 h before slaughter. Meat quality parameters were also determined. In both sexes, SC significantly increased in response to time to slaughter. There was a significant interaction of sex and time to slaughter on SeC. Gilts had higher CK levels and lower muscle L* values than boars. There were correlations among baseline SC, SeC, UC and most meat quality parameters. Time to slaughter influenced levels of SC, UC, CK and pork quality between boars and gilts. PMID- 26855164 TI - Electrochemical determination of microRNAs based on isothermal strand displacement polymerase reaction coupled with multienzyme functionalized magnetic micro-carriers. AB - MicroRNAs (miRNAs) show great potential for disease diagnostics due to their specific molecular profiles. Detection of miRNAs remains challenging and often requires sophisticated platforms. Here we report a multienzyme-functionalized magnetic microcarriers-assisted isothermal strand-displacement polymerase reaction (ISDPR) for quantitative detection of miRNAs. Magnetic micro-carriers (MMCs) were functionalized with molecular beacons to enable miRNAs recognition and magnetic separation. The target miRNAs triggered a phi29-mediated ISDPR, which can produce biotin-modified sequences on the MMCs. Streptavidin-alkaline phosphatase was then conjugated to the MMC surface through biotin-streptavidin interactions. In the presence of 2-phospho-L-ascorbic acid, miRNAs were quantitatively determined on a screen-printed carbon electrode from the anodic current of the enzymatic product. We show that this method enables detection of miRNAs as low as 9 fM and allows the discrimination of one base mismatched sequence. The proposed method was also successfully applied to analyze miRNAs in clinical tumor samples. This paper reports a new strategy for miRNAs analysis with high sensitivity, simplicity, and low cost. It would be particularly useful for rapid point-of-care testing of miRNAs in clinical laboratory. PMID- 26855165 TI - A label-free electrochemiluminescence immunosensor based on EuPO4 nanowire for the ultrasensitive detection of Prostate specific antigen. AB - EuPO4 nanowire, which exhibited strong and stable cathodic electrochemiluminescence (ECL) activity, was used for the first time to fabricate an immunosensor for the detection of prostate specific antigen (PSA). EuPO4 has some inherent excellent properties such as long luminescence lifetime, narrow emission band, high quantum yield and low toxicity. Based on these properties, a novel label-free ECL immunosensor was developed using EuPO4 as a sensing matrix. Chitosan solution was used to disperse EuPO4 nanowires and the amino groups on chitosan enabled the covalent attachment of capture antibodies. After the modification of the electrode surface with EuPO4 nanowires, anti-PSA was then immobilized on them, forming a label-free immunosensing interface. The specific binding of PSA on the electrode inhibited the ECL reaction of EuPO4 nanowires with the coreactant due to the steric hindrance effect (Deng et al., 2013). Under the optimum conditions, a good linear relationship between ECL intensity and the logarithm of PSA concentration was obtained in the range of 0.0005-80 ng/mL with a detection limit of 177.33 fg/mL. The proposed ECL immunosensor showed good stability, acceptable selectivity and reproducibility. PMID- 26855166 TI - Safe Finger Tourniquet--Ideas. AB - Tourniquets are often needed for optimized phalangeal surgeries. However, few surgeons forget to remove them and caused ischemic injuries. We have a modified method to create a safe finger tourniquet for short duration finger surgeries, which can avoid such tragedy. It is done by donning a glove, cutting the tip of the glove over the finger of interest, and rolling the glove finger to the base. From 2010 to 2013, approximately 54 patients underwent digital surgical procedures with our safe finger tourniquet. Because the glove cannot be forgotten to be removed, the tourniquet must be released and removed. This is a simple and efficient way to apply a safe finger tourniquet by using hand rubber glove for a short-term bloodless finger surgery and can achieve an excellent surgical result. PMID- 26855167 TI - Experience With the Use of Free Fasciocutaneous Flap in Through-and-Through Cheek Buccal Defect Reconstruction: Surgical Outcome and Quality of Life Analysis. AB - BACKGROUND: Through-and-through cheek-buccal soft tissue defects usually require fasciocutaneous flaps for reconstruction. However, no ideal flap has been established for reconstruction. METHODS: A retrospective chart review of head and neck reconstruction performed at Taipei Veterans General Hospital between 2003 and 2012 was conducted. Surgical outcomes and quality-of-life assessments between different fasciocutaneous flaps were collected and compared. RESULTS: Eighty-five patients received a free anterolateral thigh flap, and 25 patients received a free forearm flap. The flap success rates were 96.4% for the free anterolateral thigh flap and 96% for the free forearm flap. Appearance, swallowing, and speech were less satisfactory in long-term follow-up; and recurrent tumor, flap size (>100 cm2), oral commissure involvement, and long hospital stay (>40 days) were associated with unsatisfactory quality of life. CONCLUSIONS: Free fasciocutaneous flap can result in acceptable success rates, but patient satisfaction with appearing, swallowing, and speech function was relatively low after reconstruction. Tumor status (primary or recurrent), flap size, oral commissure involvement, and length of hospital stay are the main factors that affect quality of life. PMID- 26855168 TI - Experience of Surgical Treatment for Occipital Migraine in Taiwan. AB - PURPOSE: Refractory migraine surgery developed since 2003 has excellent results over the past 10 years. According to the pioneer of migraine surgery, Dr. Bahman Guyuron, 5 major surgical classifications of migraines are described in the field of plastic surgery, namely, frontal migraine, temporal migraine, rhinogenic migraine, occipital migraine, and auriculotemporal migraine. In this study, we present the preliminary surgical results of the occipital migraine surgery. MATERIALS AND METHODS: A total of 22 patients with simple occipital migraines came to our outpatient clinic for help from June 2014 to February 2015. Thirteen cases were excluded owing to ineligibility for operation or other reasons. The patients who concurrently experienced other types of migraines were precluded even if they received combined migraine surgery. Therefore, 9 simple occipital migraine cases were enrolled in this study. Migraine severity was evaluated by uniform questionnaires to identify the source of migraine. Neurolysis was performed under general anesthesia, with the patient in a prone position. Postoperative conditions were evaluated at the second, fourth, sixth, and eighth weeks by posttreatment questionnaires. RESULTS: Of all the 9 patients, 5 experienced single-sided migraines of greater occipital nerve origin (2 left sided and 3 right-sided cases). Two patients had bilateral migraines of greater occipital nerve origin, and unilateral right lesser occipital nerve origin was noted in one patient. The last patient had right-sided migraines of greater and lesser occipital nerve origin. As a result in the follow-up, a response rate greater than 90% was documented, and complete resolution was observed in 2 patients. Drug doses were reduced more than 50% in the remaining patients. The overall efficacy of occipital migraine surgery in this study was 88.8% (8/9 cases). CONCLUSION: Some patients with migraine are good candidates for surgical resolution with appropriate and meticulous selection. Similar to what is observed in Western countries, the migraine surgery is promising and could provide a better quality of life to selected refractory migraine patients in Taiwan. PMID- 26855169 TI - Characteristics of antiretroviral therapy-naive patients lost-to-care in HIV clinics in Democratic Republic of Congo, Cameroon, and Burundi. AB - Antiretroviral therapy (ART)-naive patients are vulnerable to becoming lost-to care (LTC) because they are not monitored as often as patients on treatment. We examined data from 19,461 HIV positive adults at 10 HIV clinics in Democratic Republic of Congo (DRC), Cameroon, and Burundi participating in the Phase 1 International epidemiologic Databases to Evaluate AIDS Central Africa (IeDEA-CA) study. Patients were LTC if they were ART-naive and did not return within 7 months of the end of data collection. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with LTC. Of 5353 ART-naive patients, 4420 (83%) were LTC and 933 (17%) were in-care. The odds of being LTC were greatest among patients from DRC (OR = 2.16, CI: 1.64 2.84, p < .0001), males (OR = 1.39, CI: 1.15-1.69, p = .0009), and ages 18-49 (OR = 1.45, CI: 1.16-1.82, p = .001). The odds of being LTC were least among patients with a WHO Clinical Stage of 1 or 2 (OR = 0.65, CI: 0.55-0.77, p < .0001) and in a perceived concordant relationship (OR = 0.61, CI: 0.43-0.87, p < .0001). LTC patients were more likely to have characteristics associated with higher risk for HIV transmission and progression. Many entered care at advanced stages and were less likely to know their partner's serostatus. Greater efforts to retain ART naive patients may increase earlier initiation of ART. PMID- 26855170 TI - International Dengue Vaccine Communication and Advocacy: Challenges and Way Forward. AB - Dengue vaccine introduction will likely occur soon. However, little has been published on international dengue vaccine communication and advocacy. More effort at the international level is required to review, unify and strategically disseminate dengue vaccine knowledge to endemic countries' decision makers and potential donors. Waiting to plan for the introduction of new vaccines until licensure may delay access in developing countries. Concerted efforts to communicate and advocate for vaccines prior to licensure are likely challenged by unknowns of the use of dengue vaccines and the disease, including uncertainties of vaccine impact, vaccine access and dengue's complex pathogenesis and epidemiology. Nevertheless, the international community has the opportunity to apply previous best practices for vaccine communication and advocacy. The following key strategies will strengthen international dengue vaccine communication and advocacy: consolidating existing coalitions under one strategic umbrella, urgently convening stakeholders to formulate the roadmap for integrated dengue prevention and control, and improving the dissemination of dengue scientific knowledge. PMID- 26855171 TI - Tripping on TRIB3 at the junction of health, metabolic dysfunction and cancer. AB - Metabolic diseases like obesity, atherosclerosis and diabetes are frequently associated with increased risk of aggressive cancers. Although metabolic dysfunctions in normal cells are manifested due to defective signaling networks that control cellular homeostasis, malignant cells utilize these signaling networks for their increased survival, growth and metastasis. Despite decades of research, a common mechanistic link between these chronic pathologies is still not well delineated. Evidences show that the unfolded protein response (UPR) and the endoplasmic reticulum stress (ERS) pathways are often dysregulated in both metabolic diseases and cancer. The UPR also triggers coordinated signaling with both PI3K/AKT/mTOR and Autophagy pathways in order to promote stress-adaptive mechanisms. Whereas, uncontrolled UPR and the resultant ERS escalates cells towards metabolic dysfunctions and ultimately cell death. In this review, we will discuss findings that implicate a crucial role for the multifunctional ERS induced protein, TRIB3. The 'pseudokinase' function of TRIB3 facilitates the inactivation of multiple transcription factors and signaling proteins. The MEK1 binding domain of TRIB3 enables it to deactivate multiple MAP-kinases. In addition, the COP1 motif of TRIB3 assists ubiquitination and proteasomal degradation of numerous TRIB3 associated proteins. The most well studied action of TRIB3 has been on the PI3K/AKT/mTOR pathway, where TRIB3-mediated inhibition of AKT phosphorylation decreases insulin signaling and cell survival. Conversely, cancer cells can either upregulate the AKT survival pathway by suppressing TRIB3 expression or alter TRIB3 localization to degrade differentiation inducing nuclear transcription factors such as C/EBPalpha and PPARgamma. The gain-of function Q84R polymorphism in TRIB3 is associated with increased risk of diabetes and atherosclerosis. TRIB3 acts as a crucial 'stress adjusting switch' that links homeostasis, metabolic disease and cancer; and is being actively investigated as a disease biomarker and therapeutic target. PMID- 26855172 TI - Pentoxifylline as a modulator of anticancer drug doxorubicin. Part II: Reduction of doxorubicin DNA binding and alleviation of its biological effects. AB - Anticancer drug doxorubicin is commonly used in cancer treatment. However, drug's severe side effects make toxicity reduction important matter. Another biologically active aromatic compound, pentoxifylline, can sequester aromatic compounds in stacking complexes reducing their bioactivity. This work deals with the problem of alleviating doxorubicin side effects by pentoxifylline. We employed a wide spectrum of prokaryotic and eukaryotic cellular assays. In addition, we used the doxorubicin-pentoxifylline mixed association constant to quantitatively assess pentoxifylline influence on the doxorubicin mutagenic activity. Obtained results indicate strong protective effects of pentoxifylline towards doxorubicin, observed on bacteria and human keratinocytes with no such effects observed on the cancer cells. It may be hypothesized that, considering much shorter half-life of pentoxifylline than doxorubicin, simultaneous administration of doxorubicin and pentoxifylline will lead to gradual release of doxorubicin from complexes with pentoxifylline to reach desired therapeutic concentration. Proposed results shed light on the possible doxorubicin chemotherapy modification and its side effects reduction without the loss of its therapeutic potential. PMID- 26855173 TI - Mechanisms of iron hepatotoxicity. PMID- 26855175 TI - Oscillators based on double-walled armchair@zigzag carbon nanotubes containing inner tubes with different helical rises. AB - A novel approach is presented to improve the oscillatory behavior of oscillators based on double-walled carbon nanotubes containing rotating inner tubes applied with different helical rises. The influence of the helical rise on the oscillatory amplitude, frequency, and stability of inner tubes with different helical rises in armchair@zigzag bitubes is investigated using the molecular dynamics method. Our simulated results show that the oscillatory behavior is very sensitive to the applied helical rise. The inner tube with h = 10 A has the most ideal hexagon after the energy minimization and NVT process in the armchair@zigzag bitubes, superior even to the inner tube without a helical rise, and thus it exhibits better oscillatory behavior compared with other modes. Therefore, we can apply an appropriate helical rise on the inner tube to produce a stable and smooth oscillator based on double-walled carbon nanotubes. PMID- 26855174 TI - Biliary fibrosis drives liver repopulation and phenotype transition of transplanted hepatocytes. AB - BACKGROUND & AIMS: Current research focuses on developing alternative strategies to restore decreased liver mass prior to the onset of end-stage liver disease. Cell engraftment/repopulation requires regeneration in normal liver, but we have shown that severe liver injury stimulates repopulation without partial hepatectomy (PH). We have now investigated whether a less severe injury, secondary biliary fibrosis, would drive engraftment/repopulation of ectopically transplanted mature hepatocytes. METHODS: Ductular proliferation and progressive fibrosis in dipeptidyl-peptidase IV (DPPIV)(-) F344 rats was induced by common bile duct ligation (BDL). Purified DPPIV(+)/green fluorescent protein (GFP)(+) hepatocytes were infused without PH into the spleen of BDL rats and compared to rats without BDL. RESULTS: Within one week, transplanted hepatocytes were detected in hepatic portal areas and at the periphery of expanding portal regions. DPPIV(+)/GFP(+) repopulating cell clusters of different sizes were observed in BDL rats but not untreated normal recipients. Surprisingly, some engrafted hepatocytes formed CK-19/claudin-7 expressing epithelial cells resembling cholangiocytes within repopulating clusters. In addition, substantial numbers of hepatocytes engrafted at the intrasplenic injection site assembled into multicellular groups. These also showed biliary "transdifferentiation" in the majority of intrasplenic injection sites of rats that received BDL but not in untreated recipients. PCR array analysis showed upregulation of osteopontin (SPP1). Cell culture studies demonstrated increased Itgbeta4, HNF1beta, HNF6, Sox 9, and CK-19 mRNA expression in hepatocytes incubated with osteopontin, suggesting that this secreted protein promotes dedifferentiation of hepatocytes. CONCLUSIONS: Our studies show that biliary fibrosis stimulates liver repopulation by ectopically transplanted hepatocytes and also stimulates hepatocyte transition towards a biliary epithelial phenotype. PMID- 26855176 TI - Estimating Causal Effects With Propensity Score Models: An Evaluation of the Touch Condom Media Campaign in Pakistan. AB - Rapid population growth in Pakistan poses major risks, including those pertinent to public health. In the context of family planning in Pakistan, the current study evaluates the Touch condom media campaign and its effects on condom-related awareness, attitudes, behavioral intention, and behavior. This evaluation relies on 3 waves of panel survey data from men married to women ages 15-49 living in urban and rural areas in Pakistan (N = 1,012): Wave 1 was March 15 to April 7, 2009; Wave 2 was August 10 to August 24, 2009; and Wave 3 was May 1 to June 13, 2010. Analysis of variance provided evidence of improvements in 10 of 11 condom related outcomes from Wave 1 to Wave 2 and Wave 3. In addition, there was no evidence of outcome decay 1 year after the conclusion of campaign advertising dissemination. To help compensate for violating the assumption of random assignment, propensity score modeling offered evidence of the beneficial effects of confirmed Touch ad recall on each of the 11 outcomes in at least 1 of 3 time lagged scenarios. By using these different time-lagged scenarios (i.e., from Wave 1 to Wave 2, from Wave 1 to Wave 3, and from Wave 2 to Wave 3), propensity score modeling permitted insights into how the campaign had time-variant effects on the different types of condom-related outcomes, including carryover effects of the media campaign. PMID- 26855177 TI - Argus II retinal prosthesis system: An update. AB - This review focuses on a description of the Argus II retinal prosthesis system (Argus II; Second Sight Medical Products, Sylmar, CA) that was approved for humanitarian use by the FDA in 2013 in patients with retinitis pigmentosa with bare or no light perception vision. The article describes the components of Argus II, the studies on the implant, and future directions. PMID- 26855178 TI - Hepatocyte nuclear factor 1 coordinates multiple processes in a model of intestinal epithelial cell function. AB - Mutations in hepatocyte nuclear factor 1 transcription factors (HNF1alpha/beta) are associated with diabetes. These factors are well studied in the liver, pancreas and kidney, where they direct tissue-specific gene regulation. However, they also have an important role in the biology of many other tissues, including the intestine. We investigated the transcriptional network governed by HNF1 in an intestinal epithelial cell line (Caco2). We used chromatin immunoprecipitation followed by direct sequencing (ChIP-seq) to identify HNF1 binding sites genome wide. Direct targets of HNF1 were validated using conventional ChIP assays and confirmed by siRNA-mediated depletion of HNF1, followed by RT-qPCR. Gene ontology process enrichment analysis of the HNF1 targets identified multiple processes with a role in intestinal epithelial cell function, including properties of the cell membrane, cellular response to hormones, and regulation of biosynthetic processes. Approximately 50% of HNF1 binding sites were also occupied by other members of the intestinal transcriptional network, including hepatocyte nuclear factor 4A (HNF4A), caudal type homeobox 2 (CDX2), and forkhead box A2 (FOXA2). Depletion of HNF1 in Caco2 cells increases FOXA2 abundance and decreases levels of CDX2, illustrating the coordinated activities of the network. These data suggest that HNF1 plays an important role in regulating intestinal epithelial cell function, both directly and through interactions with other intestinal transcription factors. PMID- 26855180 TI - Super enhancers at the miR-146a and miR-155 genes contribute to self-regulation of inflammation. AB - Inflammatory response is essential to host defense and repair, and requires tight regulation as excessive and constant inflammatory response is deleterious. We recently identified that one of the general but key mechanisms for inflammatory gene transcription regulation is controlled by the formation of super enhancers mediated by NF-kappaB, and bromodomain and extraterminal (BET) proteins. Given that microRNA transcription shares a similar mechanism to mRNA, we assume that the inflammatory microRNAs transcription could be NF-kappaB and BET bromodomain dependent. In the present study, we confirmed that inflammatory stimuli changed human umbilical vein endothelial cells (HUVEC) microRNA profile. Among these microRNAs, miR-146a and miR-155, two well-established inflammatory microRNAs, are both downregulated at transcriptional level by NF-kappaB and BET bromodomain inhibition. To pursue this mechanism, we analyzed the ChIP-seq data and found that NF-kappaB, BRD4 and RNA POL II were rapidly distributed at the upstream regions of miR-146a and miR-155, and more importantly mediated the formation of the super enhancers that drive miR-146a and miR-155 transcription. These microRNAs transcription driven by super enhancers in turn downregulate both in vitro and in vivo canonical inflammatory genes expression through targeting inflammatory mediators. This novel finding demonstrated how the host self regulates inflammatory genes expression at both transcriptional and post transcriptional level to ensure the appropriate level of the host inflammatory response. PMID- 26855181 TI - Modified alginate and gelatin cross-linked hydrogels for soft tissue adhesive. AB - Soft tissue adhesives made from natural hydrogel are attractive in clinical applications due to their excellent properties, such as high water content, good biocompatibility, low immune, good biodegradability. Hydrogels derived from natural polysaccharides and proteins are ideal components for soft tissue adhesive since they resemble the extracellular matrices of the tissue composed of various sugar and amino acids-based macromolecules. In this paper, a series of novel tissue adhesives mixed by aldehyde sodium alginate (ASA) with amino gelatin (AG) were developed and characterized. The effect of aldehyde content in ASA and amino group content in AG on the properties of ASA/AG cross-linked hydrogel was measured. The results showed the gelling time, swelling behavior and the bonding strength of the hydrogel can be tuned by varying the content of aldehyde groups in ASA and the content of amino groups in AG. The gelation time could be controlled within 4-18 min. When the aldehyde content of ASA is 75.24% and the amino content of AG is 0.61 mmol/g, the hydrogel almost has the adhesive strength equal to the commercially available adhesive fibrin glue. So, this tunable ASA/AG hydrogels in this study could be a promising candidate as soft tissue adhesive and have a wide range of biomedical applications. PMID- 26855182 TI - Combustion of a Pb(II)-loaded olive tree pruning used as biosorbent. AB - The olive tree pruning is a specific agroindustrial waste that can be successfully used as adsorbent, to remove Pb(II) from contaminated wastewater. Its final incineration has been studied in a thermobalance and in a laboratory flow reactor. The study aims at evaluating the fate of Pb during combustion, at two different scales of investigation. The flow reactor can treat samples approximately 10(2) larger than the conventional TGA. A detailed characterization of the raw and Pb(II)-loaded waste, before and after combustion is presented, including analysis of gas and solids products. The Pb(II)-loaded olive tree pruning has been prepared by a previous biosorption step in a lead solution, reaching a concentration of lead of 2.3 wt%. Several characterizations of the ashes and the mass balances proved that after the combustion, all the lead presents in the waste remained in ashes. Combustion in a flow reactor produced results consistent with those obtained in the thermobalance. It is thus confirmed that the combustion of Pb(II)-loaded olive tree pruning is a viable option to use it after the biosorption process. The Pb contained in the solid remained in the ashes, preventing possible environmental hazards. PMID- 26855179 TI - Acetylation of lysine 109 modulates pregnane X receptor DNA binding and transcriptional activity. AB - Pregnane X receptor (PXR) is a major transcriptional regulator of xenobiotic metabolism and transport pathways in the liver and intestines, which are critical for protecting organisms against potentially harmful xenobiotic and endobiotic compounds. Inadvertent activation of drug metabolism pathways through PXR is known to contribute to drug resistance, adverse drug-drug interactions, and drug toxicity in humans. In both humans and rodents, PXR has been implicated in non alcoholic fatty liver disease, diabetes, obesity, inflammatory bowel disease, and cancer. Because of PXR's important functions, it has been a therapeutic target of interest for a long time. More recent mechanistic studies have shown that PXR is modulated by multiple PTMs. Herein we provide the first investigation of the role of acetylation in modulating PXR activity. Through LC-MS/MS analysis, we identified lysine 109 (K109) in the hinge as PXR's major acetylation site. Using various biochemical and cell-based assays, we show that PXR's acetylation status and transcriptional activity are modulated by E1A binding protein (p300) and sirtuin 1 (SIRT1). Based on analysis of acetylation site mutants, we found that acetylation at K109 represses PXR transcriptional activity. The mechanism involves loss of RXRalpha dimerization and reduced binding to cognate DNA response elements. This mechanism may represent a promising therapeutic target using modulators of PXR acetylation levels. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr. Wen Xie. PMID- 26855183 TI - Phosphogypsum biotransformation by aerobic bacterial flora and isolated Trichoderma asperellum from Tunisian storage piles. AB - Aerobic microorganisms able to grow on phosphogypsum (PG), characterized by heavy metals accumulation and high acidity were investigated by enrichment cultures. The PG was used at different concentrations, varying from 20 to 200 g/L in the enrichment culture medium supplemented with compost and Tamarix roots. This treatment reduced COD and heavy metals PG concentration. An efficient isolated fungus, identified by molecular approach as Trichoderma asperellum, was able to grow on PG as the sole carbon and energy sources at the different experimented concentrations, and to increase the culture media pH of the different PG concentrations used to 8.13. This fact would be the result of alkaline compound released during the fungus PG solubilization. Besides, the heavy metals and COD removal exceeded 52% after 7 days culture. At 200 g/LPG concentration, the experimented strain was able to reduce COD by 52.32% and metals concentrations by 73% for zinc, 63.75% for iron and 50% for cadmium. This exhibited the T. asperellum efficiency for heavy metals accumulation and for phosphogypsum bioremediation. PMID- 26855184 TI - Morphology-controlled preparation and plasmon-enhanced photocatalytic activity of Pt-BiOBr heterostructures. AB - Pt-BiOBr nanosheets, microflowers, microspheres and sphere-like microflowers are controllably fabricated via a hydro(solvo)thermal treatment-photodeposition route and adjusting Br sources and solvents in the preparation systems. The simulated sunlight and visible-light photocatalytic properties of various morphological Pt BiOBr heterostructures are evaluated by the degradation of two aqueous light insensitive organic pollutants, p-nitrophenol (PNP) and tetrabromobisphenol-A (TBBPA), and the relationship between the morphological characteristics and photocatalytic properties of the Pt-BiOBr is revealed accordingly. The sphere like Pt-BiOBr microflowers and microspheres show considerably higher photocatalytic activity with respect to their microflowers and nanosheets counterparts, and their activity outperforms P25 TiO2. This excellent photoactivity is explained in terms of unique performance of BiOBr and plasmonic metal nanoparticles as well as fascinating morphological characteristics. The Pt BiOBr heterostructures can be reused four times without obvious activity loss. PMID- 26855185 TI - The mechanism study of efficient degradation of hydrophobic nonylphenol in solution by a chemical-free technology of sonophotolysis. AB - Nonylphenol is a hydrophobic endocrine disrupting compound, which can inhibit the growth of sewage bacteria in biological processes. This study investigated the degradation of 4-n-nonylphenol (NP) in water by a chemical-free technology of sonophotolysis with emphasis on the impacts of several important parameters, including light intensity, solution pH, two commonly seen inorganic ions (i.e. NO3(-) and HCO3(-)), and principally on the examination of degradation mechanisms. It was found that, solution pH could significantly influence both NP degradation efficiency and the synergistic effect of sonophotolytic process, where higher synergistic effect was obtained at more acidic condition. In addition, the presence of NO3(-) accelerated NP degradation by both acting as a photosensitizer and providing NO2 radicals, while HCO3(-) had little effect on NP degradation. Identification of intermediates of NP degradation indicated that NP sonophotolysis was mainly initiated by the formation of hydroxy-NP, and a new intermediate di-hydroxy-NP was identified for the first time ever in this study. Through thermodynamic analysis, results indicated that both ortho- and meta hydroxy-NP species can coexist in the solution but the ortho-4-NBZQ (4-nonyl benzoquinone) is dominant. In addition, the mechanism of ortho-hydroxy-NP formation was suggested by the addition of HO and H radicals. PMID- 26855186 TI - Integrated biological and advanced oxidation based treatment of hexamine bearing wastewater: Effect of cow-dung as a co-substrate. AB - This work examines the treatment of hexamethylenetetramine (HMT) bearing effluent from N, N-dinitroso pentamethylene tetra-mine producing industrial plants in India. Chemical treatment using Fenton's reagent and aerobic treatment using batch reactors with co-substrate were investigated. Aerobic batch reactors integrated with advanced oxidation process of Fenton's reagent provides effective treatment of HMT effluents. Influence of Fenton's reagent dose reaction/contact and effect of varying co-substrate with effluent initial concentration was observed. Higher dose 100 mL of Fenton's reagent with higher reaction time 20 h resulted better degradation (34.88%) of wastewater. HMT hydrolyzes in acidic environment to ammonia and formaldehyde. Formaldehyde under normal conditions is toxic for biological treatment processes. When hydrolysis and acidification in the reactors are accompanied by low pH, aerobic batch reactors with use of co substrates glucose, sucrose, and cow-dung extract separately in different proportion to wastewater ranging from 0.67 to 4.00, degraded wastewater effectively. Higher proportion of co-substrate to wastewater resulted better degradation. The relationships between nitrate, pH, turbidity and COD are discussed. PMID- 26855188 TI - Trait evolution in the slipper orchid paphiopedilum (Orchidaceae) in China. AB - The well-known orchid genus Paphiopedilum has attracted much attention from biologists because of its diverse floral traits. Although these traits have been thoroughly described, little is known about their evolutionary trajectory. In this study, we explored their evolutionary patterns and trajectory through phylogenetic analyses and close observations, and 10 characters in 21 Chinese species mapped onto an existing phylogenetic tree. Lip shape, staminode shape, petal shape, and petal width are relatively congruent with molecular phylogenies, thereby validating the existing traditional classification system. All four of those characters, along with flower number, are strongly conserved, and are significantly affected by phylogeny. By contrast, flower color (including that of the dorsal sepal, lip, and petal) is significantly convergent among those examined species and less affected by phylogeny. Therefore, this character is independent of evolution and mainly influenced by environmental factors. All of these characters are key, classical indicators when distinguishing among species within the subgenera Brachypetalum and Paphiopedilum. PMID- 26855189 TI - Animal models of psychiatric disorders. PMID- 26855187 TI - C-Type Lectin-Like Receptor 2 Suppresses AKT Signaling and Invasive Activities of Gastric Cancer Cells by Blocking Expression of Phosphoinositide 3-Kinase Subunits. AB - BACKGROUND & AIMS: C-type lectin-like receptor 2 (CLEC2) is a transmembrane receptor expressed on platelets and several hematopoietic cells. CLEC2 regulates platelet aggregation and the immune response. We investigated its expression and function in normal and transformed gastric epithelial cells from human tissues. METHODS: We performed tissue microarray analyses of gastric carcinoma samples collected from 96 patients who underwent surgery at Zhongshan Hospital of Fudan University in Shanghai, China and performed real-time polymerase chain reaction assays from an independent group of 60 patients; matched nontumor gastric mucosa tissues were used as the control. Full-length and mutant forms of CLEC2 were expressed in gastric cancer cell line (MGC80-3), or CLEC2 protein was knocked down using small-hairpin RNAs in gastric cancer cell lines (NCI-N87 and AGS). CLEC2 signaling was stimulated by incubation of cells with recombinant human podoplanin or an antibody agonist of CLEC2; cell migration and invasion were assessed by transwell and wound-healing assays. Immunoblot, immunofluorescence microscopy, and real-time polymerase chain reaction assays were used to measure expression of markers of the epithelial to mesenchymal transition and activation of signaling pathways. Immunoprecipitation experiments were performed with an antibody against spleen tyrosine kinase (SYK). Cells were injected into lateral tail vein of BALB/C nude mice; some mice were also given injections of the phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Lung and liver tissues were collected and analyzed for metastases. RESULTS: Levels of CLEC2 were higher in nontumor gastric mucosa (control) than in gastric tumor samples. Levels of CLEC2 protein in gastric tumor tissues correlated with depth of tumor invasion, metastasis to lymph node, tumor TNM stage, and 5-year survival of patients. Activation of CLEC2 in gastric cancer cells reduced their invasive activities in vitro and expression of epithelial to mesenchymal transition markers; these tumor suppressive effects of CLEC2 required SYK. CLEC2 and SYK interacted physically, and SYK maintained the stability of CLEC2 in cells. AGS cells with CLEC2 knockdown had increased levels of phosphorylated AKT and glycogen synthase kinase 3 beta, increased expression of Snail, reduced levels of E-cadherin, and formed more metastases in mice than AGS cells that expressed CLEC2; these knockdown changes were prevented by the PI3K inhibitor LY294002. Activation of CLEC2 in AGS cells reduced protein and messenger RNA levels of PI3K subunits p85 and p110; this effect was blocked by SYK inhibitor R406. Levels of CLEC2 and SYK proteins and messenger RNAs correlated in gastric tumor samples. CONCLUSIONS: CLEC2 suppresses metastasis of gastric cancer cells injected into mice, and prevents activation of AKT and glycogen synthase kinase-3 beta signaling, as well as invasiveness and expression of epithelial to mesenchymal transition markers in gastric cancer cell lines. CLEC2 prevents expression of PI3K subunits, in a SYK dependent manner. PMID- 26855190 TI - High-fat diet exacerbates cognitive rigidity and social deficiency in the BTBR mouse model of autism. AB - The global increase in rates of obesity has been accompanied by a similar surge in the number of autism diagnoses. Accumulating epidemiological evidence suggest a possible link between overweight and the risk for autism spectrum disorders (ASD), as well as autism severity. In laboratory animals, several studies have shown a connection between various environmental factors, including diet-induced obesity, and the development of autism-related behaviors. However, the effect of high-fat or imbalanced diet on a pre-existing autism-like phenotype is unclear. In this study, we employed the BTBR inbred mouse strain, a well-established mouse model for autism, to assess the impact of inadequate fattening nutrition on the autism-related behavioral phenotype. Male mice were fed by high-fat diet (HFD) or control balanced diet (control) from weaning onward, and tested in a series of behavioral assays as adults. In addition, we measured the hypothalamic expression levels of several genes involved in oxytocin and dopamine signaling, in search of a possible neurobiological underlying mechanism. As an internal control, we also employed similar metabolic and behavioral measures on neurotypical C57 mice. Compared to control-fed mice, BTBR mice fed by HFD showed marked aggravation in autism-related behaviors, manifested in increased cognitive rigidity and diminished preference for social novelty. Moreover, the total autism composite (severity) score was higher in the HFD group, and positively correlated with higher body weight. Finally, we revealed negative correlations associating dopamine signaling factors in the hypothalamus, to autism-related severity and body weight. In contrast, we found no significant effects of HFD on autism related behaviors of C57 mice, though the metabolic effects of the diet were similar for both strains. Our results indicate a direct causative link between diet-induced obesity and worsening of a pre-existing autism-related behavior and emphasize the need for adequate nutrition in ASD patients. These findings might also implicate the involvement of hypothalamic dopamine in mediating this effect. PMID- 26855191 TI - Opioid systems in the lateral hypothalamus regulate feeding behavior through orexin and GABA neurons. AB - The hypothalamus controls feeding behavior. Since central opioid systems may regulate feeding behavior, we examined the role of MU-, delta- and kappa-opioid receptors in the lateral hypothalamus (LH), the hunger center, in feeding behavior of mice. Non-selective (naloxone; 3 mg/kg, s.c.) and selective MU- (beta funaltrexamine, beta-FNA; 10 mg/kg, s.c.), delta- (naltrindole; 3 mg/kg, s.c.) and kappa- (norbinaltorphimine, norBNI; 20 mg/kg, s.c.) opioid receptor antagonists significantly decreased food intake in food-deprived mice. The injection of naloxone (20 MUg/side) into the LH significantly decreased food intake whereas the injection of naloxone (20 MUg/side) outside of the LH did not affect food intake. The injection of beta-FNA (2 MUg/side), naltrindole (1 MUg/side) or norBNI (2 MUg/side) into the LH significantly decreased food intake. Furthermore, all these antagonists significantly decreased the mRNA level of preproorexin, but not those of other hypothalamic neuropeptides. In addition, the injection of the GABAA receptor agonist muscimol (5 MUg/side) into the LH significantly decreased food intake, and this effect was abolished by the GABAA receptor antagonist bicuculline (50 MUg/side). Muscimol (1mg/kg, i.p.) decreased the mRNA level of preproorexin in the hypothalamus. Naloxone (3mg/kg, s.c.) significantly increased the GABA level in the LH and both bicuculline and the GABA release inhibitor 3-mercaptopropionic acid (3-MP, 5 MUg/side) attenuated the inhibitory effect of naloxone on feeding behavior. 3-MP also attenuated the effects of beta-FNA and norBNI, but not that of naltrindole. These results show that opioid systems in the LH regulate feeding behavior through orexin neurons. Moreover, MU- and kappa-, but not delta-, opioid receptor antagonists inhibit feeding behavior by activating GABA neurons in the LH. PMID- 26855192 TI - Violence-related content in video game may lead to functional connectivity changes in brain networks as revealed by fMRI-ICA in young men. AB - In violent video games, players engage in virtual aggressive behaviors. Exposure to virtual aggressive behavior induces short-term changes in players' behavior. In a previous study, a violence-related version of the racing game "Carmageddon TDR2000" increased aggressive affects, cognitions, and behaviors compared to its non-violence-related version. This study investigates the differences in neural network activity during the playing of both versions of the video game. Functional magnetic resonance imaging (fMRI) recorded ongoing brain activity of 18 young men playing the violence-related and the non-violence-related version of the video game Carmageddon. Image time series were decomposed into functional connectivity (FC) patterns using independent component analysis (ICA) and template-matching yielded a mapping to established functional brain networks. The FC patterns revealed a decrease in connectivity within 6 brain networks during the violence-related compared to the non-violence-related condition: three sensory-motor networks, the reward network, the default mode network (DMN), and the right-lateralized frontoparietal network. Playing violent racing games may change functional brain connectivity, in particular and even after controlling for event frequency, in the reward network and the DMN. These changes may underlie the short-term increase of aggressive affects, cognitions, and behaviors as observed after playing violent video games. PMID- 26855194 TI - Cyclosporine A Inhibits the T-bet-Dependent Antitumor Response of CD8(+) T Cells. AB - Transplant recipients face an increased risk of cancer compared with the healthy population. Although several studies have examined the direct effects of immunosuppressive drugs on cancer cells, little is known about the interactions between pharmacological immunosuppression and cancer immunosurveillance. We investigated the different effects of rapamycin (Rapa) versus cyclosporine A (CsA) on tumor-reactive CD8(+) T cells. After adoptive transfer of CD8(+) T cell receptor-transgenic OTI T cells, recipient mice received either skin grafts expressing ovalbumin (OVA) or OVA-expressing B16F10 melanoma cells. Animals were treated daily with Rapa or CsA. Skin graft rejection and tumor growth as well as molecular and cellular analyses of skin- and tumor-infiltrating lymphocytes were performed. Both Rapa and CsA were equally efficient in prolonging skin graft survival when applied at clinically relevant doses. In contrast to Rapa-treated animals, CsA led to accelerated tumor growth in the presence of adoptively transferred tumor-reactive CD8(+) OTI T cells. Further analyses showed that T-bet was downregulated by CsA (but not Rapa) in CD8(+) T cells and that cancer cytotoxicity was profoundly inhibited in the absence of T-bet. CsA reduces T-bet dependent cancer immunosurveillance by CD8(+) T cells. This may contribute to the increased cancer risk in transplant recipients receiving calcineurin inhibitors. PMID- 26855195 TI - The History of Articulators: The Contributions of Rudolph L. Hanau and His Company-Part II. AB - This article is an historical overview of the Hanau Engineering Company from the time of Rudolph Hanau's death in 1930 to the present. It explores the development of many articulators intended both for removable and fixed prosthodontic restorations. The article is divided into the eras of the company's corporate history, and it reviews articulator designs and major improvements made during each of those periods. PMID- 26855196 TI - Topochemical Nitridation with Anion Vacancy-Assisted N(3-)/O(2-) Exchange. AB - We present how the introduction of anion vacancies in oxyhydrides enables a route to access new oxynitrides, by conducting ammonolysis of perovskite oxyhydride EuTiO3-xHx (x ~ 0.18). At 400 degrees C, similar to our studies on BaTiO3-xHx, hydride lability enables a low temperature direct ammonolysis of EuTi(3.82+)O2.82H0.18, leading to the N(3-)/H(-)-exchanged product EuTi(4+)O2.82N0.12?0.06. When the ammonolysis temperature was increased up to 800 degrees C, we observed a further nitridation involving N(3-)/O(2-) exchange, yielding a fully oxidized Eu(3+)Ti(4+)O2N with the GdFeO3-type distortion (Pnma) as a metastable phase, instead of pyrochlore structure. Interestingly, the same reactions using the oxide EuTiO3 proceeded through a 1:1 exchange of N(3-) with O(2-) only above 600 degrees C and resulted in incomplete nitridation to EuTiO2.25N0.75, indicating that anion vacancies created during the initial nitridation process of EuTiO2.82H0.18 play a crucial role in promoting anion (N(3 )/O(2-)) exchange at high temperatures. Hence, by using (hydride-induced) anion deficient precursors, we should be able to expand the accessible anion composition of perovskite oxynitrides. PMID- 26855197 TI - A mode of action of glucosinolate-derived isothiocyanates: Detoxification depletes glutathione and cysteine levels with ramifications on protein metabolism in Spodoptera littoralis. AB - Glucosinolates are activated plant defenses common in the order Brassicales that release isothiocyanates (ITCs) and other hydrolysis products upon tissue damage. The reactive ITCs are toxic to insects resulting in reduced growth, delayed development and occasionally mortality. Generalist lepidopteran larvae often detoxify ingested ITCs via conjugation to glutathione (GSH) and survive on low glucosinolate diets, but it is not known how this process influences other aspects of metabolism. We investigated the impact of the aliphatic 4 methylsulfinylbutyl-ITC (4msob-ITC, sulforaphane) on the metabolism of Spodoptera littoralis larvae, which suffer a significant growth decline on 4msob-ITC containing diets while excreting ITC-glutathione conjugates and their derivatives in the frass. The most striking effects were a decrease of GSH in midgut tissue and hemolymph due to losses by conjugation to ITC during detoxification, and a decline of the GSH biosynthetic precursor cysteine. Protein content was likewise reduced by ITC treatment suggesting that protein is actively catabolized in an attempt to supply cysteine for GSH biosynthesis. The negative growth and protein effects were relieved by dietary supplementation with cystine. Other consequences of protein breakdown included deamination of amino acids with increased excretion of uric acid and elevated lipid content. Thus metabolic detoxification of ITCs provokes a cascade of negative effects on insects that result in reduced fitness. PMID- 26855193 TI - Human dermal fibroblasts in psychiatry research. AB - In order to decipher the disease etiology, progression and treatment of multifactorial human brain diseases we utilize a host of different experimental models. Recently, patient-derived human dermal fibroblast (HDF) cultures have re emerged as promising in vitro functional system for examining various cellular, molecular, metabolic and (patho)physiological states and traits of psychiatric disorders. HDF studies serve as a powerful complement to postmortem and animal studies, and often appear to be informative about the altered homeostasis in neural tissue. Studies of HDFs from patients with schizophrenia (SZ), depression, bipolar disorder (BD), autism, attention deficit and hyperactivity disorder and other psychiatric disorders have significantly advanced our understanding of these devastating diseases. These reports unequivocally prove that signal transduction, redox homeostasis, circadian rhythms and gene*environment (G*E) interactions are all amenable for assessment by the HDF model. Furthermore, the reported findings suggest that this underutilized patient biomaterial, combined with modern molecular biology techniques, may have both diagnostic and prognostic value, including prediction of response to therapeutic agents. PMID- 26855199 TI - Ancestral gene duplication enabled the evolution of multifunctional cellulases in stick insects (Phasmatodea). AB - The Phasmatodea (stick insects) have multiple, endogenous, highly expressed copies of glycoside hydrolase family 9 (GH9) genes. The purpose for retaining so many was unknown. We cloned and expressed the enzymes in transfected insect cell lines, and tested the individual proteins against different plant cell wall component poly- and oligosaccharides. Nearly all isolated enzymes were active against carboxymethylcellulose, however most could also degrade glucomannan, and some also either xylan or xyloglucan. The latter two enzyme groups were each monophyletic, suggesting the evolution of these novel substrate specificities in an early ancestor of the order. Such enzymes are highly unusual for Metazoa, for which no xyloglucanases had been reported. Phasmatodea gut extracts could degrade multiple plant cell wall components fully into sugar monomers, suggesting that enzymatic breakdown of plant cell walls by the entire Phasmatodea digestome may contribute to the Phasmatodea nutritional budget. The duplication and neofunctionalization of GH9s in the ancestral Phasmatodea may have enabled them to specialize as folivores and diverge from their omnivorous ancestors. The structural changes enabling these unprecedented activities in the cellulases require further study. PMID- 26855198 TI - A three amino acid deletion in the transmembrane domain of the nicotinic acetylcholine receptor alpha6 subunit confers high-level resistance to spinosad in Plutella xylostella. AB - Spinosad is a macrocyclic lactone insecticide that acts primarily at the nicotinic acetylcholine receptors (nAChRs) of target insects. Here we describe evidence that high levels of resistance to spinosad in the diamondback moth (Plutella xylostella) are associated with a three amino acid (3-aa) deletion in the fourth transmembrane domain (TM4) of the nAChR alpha6 subunit (Pxalpha6). Following laboratory selection with spinosad, the SZ-SpinR strain of P. xylostella exhibited 940-fold resistance to spinosad. In addition, the selected insect population had 1060-fold cross-resistance to spinetoram but, in contrast, no cross-resistance to abamectin was observed. Genetic analysis indicates that spinosad resistance in SZ-SpinR is inherited as a recessive and autosomal trait, and that the 3-aa deletion (IIA) in TM4 of Pxalpha6 is tightly linked to spinosad resistance. Because of well-established difficulties in functional expression of cloned insect nAChRs, the analogous resistance-associated deletion mutation was introduced into a prototype nAChR (the cloned human alpha7 subunit). Two electrode voltage-clamp recording with wild-type and mutated nAChRs expressed in Xenopus laevis oocytes indicated that the mutation causes a complete loss of agonist activation. In addition, radioligand binding studies indicated that the 3 aa deletion resulted in significantly lower-affinity binding of the extracellular neurotransmitter-binding site. These findings are consistent with the 3-amino acid (IIA) deletion within the transmembrane domain of Pxalpha6 being responsible for target-site resistance to spinosad in the SZ-SpinR strain of P. xylostella. PMID- 26855201 TI - Knowledge of Cancer Stage among Women with Nonmetastatic Breast Cancer. AB - BACKGROUND: Discrepancies may exist between what oncologists communicate and what patients understand about their cancer stage and its implications. OBJECTIVE: We explored patients' ability to identify their stage of breast cancer. METHODS: As part of a study testing a cancer self-management intervention we asked women to identify their stage of disease and compared responses to the electronic medical record (EMR) for validation. The sample included women with recently diagnosed nonmetastatic (stage I-III) disease. We calculated descriptive statistics and used logistic regression to examine relationships between knowledge of stage, demographic and clinical variables, and study outcomes. Measurement instruments were the Control Preferences Scale (CPS), Knowledge of Care Options Test (KOCO), Measurement of Transitions Scale (MOT), Medical Communication Competence Scale (MCCS), Chronic Disease Self-Efficacy Scale (CDSE), Uncertainty in Illness Scale (MUIS-C), and Hospital Anxiety and Depression Scale (HADS). RESULTS: Participants (n = 98) had a mean age of 52.3 years (range 27-72). Per the EMR, 19 participants (19.4%) had stage I breast cancer, 56 (57.1%) had stage II, and 23 (23.5%) had stage III. Of the 28 participants (28.6%) unable to identify their stage of cancer correctly, 11 (39.3%) provided vague responses, 11 (39.3%) reported an incorrect stage, and 6 (21.4%) did not know their stage. Younger age (p = 0.0412) and earlier cancer stage (p = 0.0136) were predictive of correctly identifying stage. Participants who at baseline had a greater knowledge of care options (curative, palliative, and hospice care) were more likely to correctly identify their stage (KOCO, p = 0.0345). CONCLUSIONS: Clinicians should revisit conversations about cancer stage and care options to ensure patients' understanding and support self-management. PMID- 26855202 TI - 1,3-Diazasilabicyclo[1.1.0]butane with a Long Bridging N-N Bond. AB - A 1,3-diazasilabicyclo[1.1.0]butane (1) is synthesized as thermally stable crystals by using the cycloaddition reaction of an isolable dialkylsilylene with aziadamantane. The bridge N-N bond length of 1 (1.70 A) is the longest among those of known N-N singly-bonded compounds, including side-on bridged transition metal dinitrogen complexes. The compound 1 is intact in air but moisture sensitive. No reaction occurs with hydrogen, even under pressure at 0.5 MPa. Irradiation of 1 with light gives an isomer quantitatively by N-N and adamantyl C C bond cleavage. The origin of the remarkable N-N bond elongation is ascribed to significant interaction between a Si-C sigma* and Nu-Nu pi and sigma orbitals as determined by DFT calculations of model compounds. PMID- 26855203 TI - Molecularly Tuning the Radicaloid N-H...O?C Hydrogen Bond. AB - Substituent effects on the open shell N-H...O?C hydrogen-bond has never been reported. This study examines how 12 functional groups composed of electron donating groups (EDG), halogen atoms and electron withdrawing groups (EWG) affect the N-H...O?C hydrogen-bond properties in a six-membered cyclic model system of O?C(Y)-CH?C(X)N-H. It is found that group effects on this open shell H-bonding system are significant and have predictive trends when X = H and Y is varied. When Y is an EDG, the N-H...O?C hydrogen-bond is strengthened; and when Y is an EWG, the bond is weakened; whereas the variation in electronic properties of X group do not exhibit a significant impact upon the hydrogen bond strength. The structural impact of the stronger N-H...O?C hydrogen-bond are (1) shorter H and O distance, r(H...O) and (2) a longer N-H bond length, r(NH). The stronger N H...O?C hydrogen-bond also acts to pull the H and O in toward one another which has an effect on the bond angles. Our findings show that there is a linear relationship between hydrogen-bond angle and N-H...O?C hydrogen-bond energy in this unusual H-bonding system. In addition, there is a linear correlation of the r(H...O) and the hydrogen bond energy. A short r(H...O) distance corresponds to a large hydrogen bond energy when Y is varied. The observed trends and findings have been validated using three different methods (UB3LYP, M06-2X, and UMP2) with two different basis sets. PMID- 26855204 TI - GAGG:ce single crystalline films: New perspective scintillators for electron detection in SEM. AB - Single crystal scintillators are frequently used for electron detection in scanning electron microscopy (SEM). We report gadolinium aluminum gallium garnet (GAGG:Ce) single crystalline films as a new perspective scintillators for the SEM. For the first time, the epitaxial garnet films were used in a practical application: the GAGG:Ce scintillator was incorporated into a SEM scintillation electron detector and it showed improved image quality. In order to prove the GAGG:Ce quality accurately, the scintillation properties were examined using electron beam excitation and compared with frequently used scintillators in the SEM. The results demonstrate excellent emission efficiency of the GAGG:Ce single crystalline films together with their very fast scintillation decay useful for demanding SEM applications. PMID- 26855205 TI - 3D imaging by serial block face scanning electron microscopy for materials science using ultramicrotomy. AB - Mechanical serial block face scanning electron microscopy (SBFSEM) has emerged as a means of obtaining three dimensional (3D) electron images over volumes much larger than possible by focused ion beam (FIB) serial sectioning and at higher spatial resolution than achievable with conventional X-ray computed tomography (CT). Such high resolution 3D electron images can be employed for precisely determining the shape, volume fraction, distribution and connectivity of important microstructural features. While soft (fixed or frozen) biological samples are particularly well suited for nanoscale sectioning using an ultramicrotome, the technique can also produce excellent 3D images at electron microscope resolution in a time and resource-efficient manner for engineering materials. Currently, a lack of appreciation of the capabilities of ultramicrotomy and the operational challenges associated with minimising artefacts for different materials is limiting its wider application to engineering materials. Consequently, this paper outlines the current state of the art for SBFSEM examining in detail how damage is introduced during slicing and highlighting strategies for minimising such damage. A particular focus of the study is the acquisition of 3D images for a variety of metallic and coated systems. PMID- 26855200 TI - Rechargeable anticandidal denture material with sustained release in saliva. AB - OBJECTIVE: Candida-induced denture stomatitis is a common debilitating problem among denture wearers. Previously, we described the fabrication of a new denture material that released antifungal drugs when immersed in phosphate buffered saline. Here, we use more clinically relevant immersion conditions (human saliva; 37 degrees C) and measure miconazole release and bioactivity. MATERIALS AND METHODS: Disks were prepared by grafting PNVP [poly(N-vinyl-2-pyrrolidinone)] onto PMMA [poly(methylmethacrylate)] using plasma initiation (PMMA-g-PNVP) and then loaded with miconazole. Drug-loaded disks were immersed in 10-100% human saliva (1-30 days). Miconazole release was measured and then tested for bioactivity vs miconazole-sensitive and miconazole-resistant Candida isolates. RESULTS: HPLC was used to quantify miconazole levels in saliva. Miconazole-loaded disks released antifungal drug for up to 30 days. Higher drug release was found with higher concentrations of saliva, and, interestingly, miconazole solubility was increased with higher saliva concentrations. The released miconazole retained its anticandidal activity. After immersion, the residual miconazole could be quenched and the disks recharged. Freshly recharged disks displayed the same release kinetics and bioactivity as the original disks. Quenched disks could also be charged with chlorhexidine that displayed anticandidal activity. CONCLUSIONS: These results suggest that PMMA-g-PNVP is a promising new denture material for long-term management of denture stomatitis. PMID- 26855206 TI - Direct investigation of (sub-) surface preparation artifacts in GaAs based materials by FIB sectioning. AB - The introduction of preparation artifacts is almost inevitable when producing samples for (scanning) transmission electron microscopy ((S)TEM). These artifacts can be divided in extrinsic artifacts like damage processes and intrinsic artifacts caused by the deviations from the volume strain state in thin elastically strained material systems. The reduction and estimation of those effects is of great importance for the quantitative analysis of (S)TEM images. Thus, optimized ion beam preparation conditions are investigated for high quality samples. Therefore, the surface topology is investigated directly with atomic force microscopy (AFM) on the actual TEM samples. Additionally, the sectioning of those samples by a focused ion beam (FIB) is used to investigate the damage depth profile directly in the TEM. The AFM measurements show good quantitative agreement of sample height modulation due to strain relaxation to finite elements simulations. Strong indications of (sub-) surface damage by ion beams are observed. Their influence on high angle annular dark field (HAADF) imaging is estimated with focus on thickness determination by absolute intensity methods. Data consolidation of AFM and TEM measurements reveals a 3.5nm surface amorphization, negligible surface roughness on the scale of angstroms and a sub surface damage profile in the range of up to 8.0nm in crystalline gallium arsenide (GaAs) and GaAs-based ternary alloys. A correction scheme for thickness evaluation of absolute HAADF intensities is proposed and applied for GaAs based materials. PMID- 26855207 TI - Analysis of salicylic acid, arbutin and corticosteroids in skin whitening creams available in Pakistan using chromatographic techniques. AB - BACKGROUND: A simple, new and efficient reversed-phase high-performance liquid chromatography method was developed and validated for the separation of most popular ingredients in skin whitening creams. METHODS: For RP-HPLC analysis, a Hibar((r)) C18 250 mm * 4.6 mm, 5 MUm column (Merck Millipore, Carolina, USA) as stationary phase with a mobile phase consisting a mixture of acetonitrile, methanol and water 40 : 40 : 20 (pH 7.0), respectively, at flow rate of 0.8 mL min(-1) (total run time 10 min) at room temperature was used. Detection was performed at 254 and 280 nm using photodiode array detector. The method was validated in accordance with ICH guidelines with respect to linearity, accuracy, precision, specificity, limit of detection and quantification. RESULTS: The method results in excellent separation of skin whitening agents in cosmetic creams. The method is specific for salicylic acid, arbutin, cortisone, hydrocortisone, betamethasone valerate and betamethasone dipropionate. The calibration curve of skin whitening agents was linear with the regression analysis showed r(2) >= 0.999. %RSD for inter- and intraday precision were determined as 0.461 and 0.329 for salicylic acid, 0.427 and 0.317 for arbutin, 0.360 and 0.346 for cortisone, 0.336 and 0.350 for hydrocortisone, 0.463 and 0.339 for betamethasone valerate and 0.385 and 0.372 for betamethasone dipropionate, respectively. LOD and LOQ were calculated as 0.48 and 1.20 MUg mL( 1) for salicylic acid, 0.09 and 0.22 MUg mL(-1) for arbutin, 0.07 and 0.18 MUg mL(-1) for cortisone, 0.06 and 0.24 MUg mL(-1) for hydrocortisone, 0.07 and 0.20 MUg mL(-1) for betamethasone valerate and 0.02 and 0.06 MUg mL(-1) for betamethasone dipropionate. The recovery of skin whitening agents were 97.18% for salicylic acid, 97.99% for arbutin, 98.30% cortisone, 97.63% for hydrocortisone, 98.65% for betamethasone valerate and 98.18% for betamethasone dipropionate, respectively. According to this study, salicylic acid is present in 87.88% skin whitening creams, arbutin in 96.97%, cortisone in 60.60%, hydrocortisone in 48.48%, betamethasone valerate in 15.15% and betamethasone dipropionate present in 12.12% cosmetic creams available in Pakistan. PMID- 26855208 TI - Potential of ceramide 1-phosphate as a novel therapeutic agent in pulmonary inflammation. PMID- 26855209 TI - Ozonation of the UV filter benzophenone-4 in aquatic environments: Intermediates and pathways. AB - The occurrence of benzophenone-4 (BP-4) in water environments may pose a serious public health hazard due to its potential endocrine disrupting effects. In this work, the intermediates, probable degradation pathways and toxicity changes during ozonation of BP-4 in aqueous solution were systematically investigated. Results revealed that alkaline conditions favored the oxidation of BP-4. However, inorganic anions (Cl(-), NO3(-), SO4(2-)), cations (K(+), Ca(2+), Mg(2+)) and humic acid had no remarkable effect on BP-4 removal within the tested concentrations. Ozonation was also effective for the fast removal of BP-4 in real waters. The TOC suggested a low mineralization rate, even after the complete BP-4 removal. Meanwhile, the treated mixtures exhibited an obvious inhibition to the bioluminescent bacteria Photobacterium phosphoreum, indicating the formation of transformation products with higher toxicities. Furthermore, fourteen products were identified by means of liquid chromatography-mass spectrometry. Notably, seven of them have not been reported previously. The quenching test indicated that the degradation processes probably were dominated by OH. Next, possible degradation pathways were proposed and further justified by theoretical calculations of frontier electron densities. This investigation will contribute to the systematic elucidation of the ozonation process of UV filters in aquatic environments. PMID- 26855210 TI - Cytotoxicity and colloidal behavior of polystyrene latex nanoparticles toward filamentous fungi in isotonic solutions. AB - The effects of surface physicochemical properties of functionalized polystyrene latex (PSL) nanoparticles (NPs) and model filamentous fungi Aspergillus oryzae and Aspergillus nidulans cultivated in different environment (aqueous and atmospheric environment) on the colloidal behavior and cytotoxicity were investigated in different isotonic solutions (154 mM NaCl and 292 mM sucrose). When the liquid cultivated fungal cells were exposed to positively charged PSL NPs in 154 mM NaCl solution, the NPs were taken into A. oryzae, but not A. nidulans. Atomic force microscopy revealed that the uptake of NPs was more readily through the cell wall of A. oryzae because of its relatively softer cell wall compared with A. nidulans. In contrast, the positively charged PSL NPs entirely covered the liquid cultivated fungal cell surfaces and induced cell death in 292 mM sucrose solution because of the stronger electrostatic attractive force between the cells and NPs compared with in 154 mM NaCl. When the agar cultivated fungal cells were exposed to the positively charged PSL NPs, both fungal cells did not take the NPs inside the cells. Contact angle measurement revealed that the hydrophobin on the agar cultivated cell surfaces inhibited the uptake of NPs because of its relatively more hydrophobic cell surface compared with the liquid cultivated cells. PMID- 26855211 TI - Distribution and ecological risk assessment of polycyclic aromatic hydrocarbons in water, suspended particulate matter and sediment from Daliao River estuary and the adjacent area, China. AB - Polycyclic aromatic hydrocarbons (PAHs) contamination was investigated in concurrently sampled surface water, suspended particulate matter (SPM) and sediment of Daliao River estuary and the adjacent area, China. The total concentrations of PAHs ranged from 71.12 to 4255.43 ng/L in water, from 1969.95 to 11612.21 ng/L in SPM, and from 374.84 to 11588.85 ng/g dry weight (dw) in sediment. Although the 2-3 ring PAHs were main PAH congeners in water and SPM, the 4-6 ring PAHs were also detected and their distribution was site-specific, indicating a very recent PAHs input around the area since they were hydrophobic. The PAHs pollution was identified as mixed combustion and petroleum sources. Based on species sensitivity distribution (SSD), the ecological risk in SPM from 82% stations was found to be higher obviously than that in water. The risk in water was basically ranked as medium, while the risk in SPM was ranked as high. Analysis with sediment quality guidelines (SQGs) indicated that negative eco-risk occasionally occurred in about 50% stations, while negative eco-risk frequently occurred in about 3% stations only caused by Phenanthrene(Phe) and Dibenzo(a,h)anthracene(DBA). Here freshwater acute effects data together with saltwater data were used for SSD model. And this method could quickly give the rational risk information, and achieved our objective that compared the spatial difference of risk levels among three compartments. The results confirmed that the use of freshwater acute effects data from the ECOTOX database together with saltwater effects data is acceptable for risk assessment purposes in estuary. PMID- 26855212 TI - Spatial variability versus parameter uncertainty in freshwater fate and exposure factors of chemicals. AB - We compared the influence of spatial variability in environmental characteristics and the uncertainty in measured substance properties of seven chemicals on freshwater fate factors (FFs), representing the residence time in the freshwater environment, and on exposure factors (XFs), representing the dissolved fraction of a chemical. The influence of spatial variability was quantified using the SimpleBox model in which Europe was divided in 100 * 100 km regions, nested in a regional (300 * 300 km) and supra-regional (500 * 500 km) scale. Uncertainty in substance properties was quantified by means of probabilistic modelling. Spatial variability and parameter uncertainty were expressed by the ratio k of the 95%ile and 5%ile of the FF and XF. Our analysis shows that spatial variability ranges in FFs of persistent chemicals that partition predominantly into one environmental compartment was up to 2 orders of magnitude larger compared to uncertainty. For the other (less persistent) chemicals, uncertainty in the FF was up to 1 order of magnitude larger than spatial variability. Variability and uncertainty in freshwater XFs of the seven chemicals was negligible (k < 1.5). We found that, depending on the chemical and emission scenario, accounting for region-specific environmental characteristics in multimedia fate modelling, as well as accounting for parameter uncertainty, can have a significant influence on freshwater fate factor predictions. Therefore, we conclude that it is important that fate factors should not only account for parameter uncertainty, but for spatial variability as well, as this further increases the reliability of ecotoxicological impacts in LCA. PMID- 26855213 TI - Long-term exposure of rabbits to imidaclorpid as quantified in blood induces genotoxic effect. AB - The present in-vivo study focuses on the genotoxic effect of the neonicotinoid pesticide imidacloprid (IMI) in rabbits. The purpose of the study was to establish a possible relationship between exposure to the pesticide (dose and duration) and genotoxicity. Furthermore, an analytical method for the simultaneous determination of IMI and its major metabolite 6-chloronicotinic acid (6-ClNA) in blood was developed and validated. The isolation of the two analytes from blood was performed by liquid-liquid extraction with dichloromethane. Analysis was performed by Liquid Chromatography - Atmospheric Pressure Chemical Ionization - Mass Spectrometry (LC-APCI-MS). The method was applied on the determination of IMI and 6-ClNA in serum samples obtained from rabbits fed with the insecticide at two low doses. Furthermore, parameters of genotoxicity and cytotoxicity were evaluated by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the Cytokinesis Block Proliferation Index (CBPI), in lymphocytes of exposed rabbits. The results revealed a genotoxic effect of IMI for both exposed groups. There were statistically significant differences in the frequencies of BNMN and MN between control and exposed groups but there was no dose-dependence, neither time-dependence of the genotoxic effect for the administered doses. This is the first time that long term exposure to IMI in rabbits was studied for the determination of its genotoxic effect. The genotoxic effect of IMI as it is depicted by the current study is in accordance with previous studies. PMID- 26855214 TI - OH radical generation in a photocatalytic reactor using TiO2 nanotube plates. AB - In order to use TiO2 nanotubes grown on a Ti plate as a photocatalyst, self organized oxide nanotube layers were grown by anodization in a glycerol based electrolyte. The ultimate conditions for the synthesis of the TiO2 nanotube array on the Ti plate were investigated by comparing the morphology, length, and inner diameter of the nanotubes. They were significantly affected by the applied anodic voltage, anodization time, and composition of the electrolyte such as the water and fluoride ion concentration. The crystallographic structures of TiO2 nanotubes before and after annealing were compared. The photocatalytic reactor used in this study consisted of two parallel and closely spaced TiO2 nanotube plates. The plates were squares while a UV lamp was inserted perpendicularly to them. OH radical generation in the photocatalytic reactor was monitored by using a probe compound, parachlorobenzoate (pCBA). The steady state OH radical concentration was compared depending on the length of nanotubes and crystallographic structure. The longer the nanotubes, the higher the steady state OH radical concentration. PMID- 26855215 TI - Biomethane recovery from Egeria densa in a microbial electrolysis cell-assisted anaerobic system: Performance and stability assessment. AB - Renewable energy recovery from submerged aquatic plants such as Egeria densa (E. densa) via continuous anaerobic digestion (AD) represents a bottleneck because of process instability. Here, a single-chamber membrane-free microbial electrolysis cell (MEC) equipped with a pair of Ti/RuO2 mesh electrodes (i.e. the combined MEC AD system) was implemented at different applied voltages (0-1.0 V) to evaluate the potential effects of bioelectrochemical stimulation on methane production and process stability of E. densa fermentation. The application of MEC effectively stabilized E. densa fermentation and upgraded overall process performance, especially solid matters removal. E. densa AD process was operated steadily throughout bioelectrochemical process without any signs of imbalance. The solubilization-removal of solid matters and methane conversion efficiency gradually increased with increasing applied voltage, with an average methane yield of approximately 248.2 +/- 21.0 mL L(-1) d(-1) at 1.0 V. Whereas, the stability of the process became worse immediately once the external power was removed, with weaken solid matters removal along with methane output, evidencing the favorable and indispensable role in maintaining process stability. The stabilizing effect was further quantitatively demonstrated by statistical analysis using standard deviation (SD), coefficient of variance (CV) and box plots. The syntrophic and win-win interactions between fermenting bacteria and electroactive bacteria might have contributed to the improved process stability and bioenergy recovery. PMID- 26855216 TI - Effect and localization of phenanthrene in maize roots. AB - Polycyclic aromatic hydrocarbons (PAHs) have a toxic effect on plants, which limits the efficiency of phytomanagement of contaminated soils. The mechanisms underlying their toxicity are not fully understood. A cultivation experiment was carried out with maize, used as model plant, exposed to sand spiked with phenanthrene (50 or 150 mg kg(-1) dw). Epi-fluorescence microscopic observation of root sections was used to assess suberization of exodermis and endodermis and phenanthrene localization along the primary root length. For 10 days of cultivation, exodermis and endodermis suberization of exposed maize was more extensive. However, after 20 days of exposure, exodermis and endodermis of non exposed roots were totally suberized, whilst PHE-exposed roots where less suberized. Early extensive suberization may act as barrier against PHE penetration, however longer exposure inhibits root maturation. Phenanthrene patches were located only near suberized exodermis and endodermis, which may therefore act as retention zones, where the hydrophobic phenanthrene accumulates during its radial transport. PMID- 26855217 TI - A nanoremediation strategy for the recovery of an As-polluted soil. AB - The present study investigates the impact of the nanoremediation treatment on soil recovery as evaluated by the development of barley plants. Highly As polluted brownfield soil was treated with nanoscale zero-valent iron (nZVI) commercial suspension at two doses (1% and 10%). Barley plants were cultivated in treated and untreated soils in a growth chamber, and the As, Fe, and nutrients uptake were determined. The efficacy of As immobilization was evaluated according to the toxicity characteristics leaching procedure (TCLP) as well as using a sequential extraction procedure. The application of nZVI reduced the amount of As in the more available fractions and increased the amount of As in the residual fraction. The best immobilization results were obtained for the highest dose of nZVI (10%). In turn, the lower availability of As in nZVI-treated soils, particularly at the dose of 10%, stimulated the development of the barley plants and decreased the As uptake. Neither an important increase of available Fe nor negative impact on soil physico-chemical and biological properties were observed. Thus, our results show that the use of nZVI could be an adequate strategy to recover the land use in As polluted soils. PMID- 26855218 TI - Study of metal transport through pine bark for reutilization as a biosorbent. AB - The potential utilization of pine bark as a biosorbent for the treatment of metal contaminated soils and waters has been evaluated in transport experiments using laboratory columns. Solutions containing the metals Cu, Pb, Zn, Ni or Cd, each one individually and at three different concentrations (2.5, 10 and 25 mM) were tested. Pine bark affected metal transport and the breakthrough curves, producing a reduction of their concentrations in the solution and a clear retardation with respect to an inert tracer. At metal concentrations equal to 2.5 mM, 100% of the assayed elements were removed from the solution in the pine bark column. At the 10 mM metal concentration, the percentage of metals retained fell to 38-67% of the amount added, whereas at the 25 mM metal concentration, only 16-43% was retained. In all cases, the highest retention capacity corresponded to Pb, and the lowest to Zn, whereas Cu, Cd and Ni produced intermediate comparable results. The analysis of the pine bark within the columns after the transport experiment showed that the metals entering the column adsorb progressively until a saturation concentration is reached in the whole column, and only then they can be released at significant concentrations. This saturation concentration was approximately 70 mmol kg(-1) for Cd, Ni and Zn, 100 mmol kg(-1) for Cu, and 125 mmol kg(-1) for Pb. Overall, our experiments have shown the high effectiveness of pine bark to retain the assayed metals in stable forms of low mobility. PMID- 26855219 TI - Laboratory testing on the removal of the veterinary antibiotic doxycycline during long-term liquid pig manure and digestate storage. AB - The veterinary antibiotic doxycycline (DOXY) is today frequently applied in conventional pig husbandry for the control of respiratory diseases. After the treatment, pigs excrete major amounts of DOXY as the unchanged active substance. Thus, DOXY residues were found in liquid manures and digestates of biogas plants at concentrations of mg kg(-1) dry weight. In order to assess the impact of field applications of contaminated manures and digestates on the entry of DOXY residues into arable and grassland soils, thorough information about the removal of DOXY during long-term storage of farm fertilizers is required. Since this aspect has been only less investigated for manures but not for digestates, first long-term storage simulation tests were performed at laboratory scale. Within the 170-d incubation periods under strictly anaerobic conditions, doxycycline was removed in liquid pig manure by 61% and in digestate by 76%. The calculated half-lives of 120 d and 91 d thus emphasized the persistence of doxycycline in both matrices. Due to the substance specific properties of DOXY, this removal was caused neither by mineralization, epimerization nor biotransformation. According to the high affinity of DOXY to manure and digestate solids, however, the formation of non extractable residues has to be taken into account as the predominant concentration determining process. This was indicated by the sequential extraction procedure applied. Hence, these results confirmed that a full removal capacity for doxycycline cannot be reached through the long-term storage of farm fertilizers. PMID- 26855220 TI - Levels of metals in kidney, liver and muscle tissue and their relation to the occurrence of parasites in the red fox in the Lower Silesian Forest in Europe. AB - Together with the occurrence of parasites, increased concentrations of xenobiotics, to which scavengers are greatly exposed, may significantly influence the physiology of red foxes. It is also suspected that these two factors interact. The accumulation of various metals (Ca, Cd, Cu, Fe, Hg, K, Mg, Ni, Pb, Zn) in kidney, liver and muscle tissue was investigated, as well as the occurrence of parasites, and the potential link to the presence of metals. Generally speaking, neither sex nor age influenced these concentrations. K, Mg and Fe were found in the highest concentrations and Hg was found in the lowest. Various relationships between the concentrations of metals were observed in the tissues. 34% of the specimens studied were hosts to parasites. No clear, significant connection between the concentrations and the occurrence of parasites was noted, but the discernible trend confirmed by the logistic regression, needs further study. PMID- 26855221 TI - Tetracycline adsorption onto activated carbons produced by KOH activation of tyre pyrolysis char. AB - Tyre pyrolysis char (TPC), produced when manufacturing pyrolysis oil from waste tyre, was used as raw material to prepare activated carbons (ACs) by KOH activation. KOH to TPC weight ratios (W) between 0.5 and 6, and activation temperatures from 600 to 800 degrees C, were used. An increase in W resulted in a more efficient development of surface area, microporosity and mesoporosity. Thus, ACs derived from TPC (TPC-ACs) with specific surface areas up to 814 m(2) g(-1) were obtained. TPC, TPC-ACs and a commercial AC (CAC) were tested for removing Tetracycline (TC) in aqueous phase, and systematic adsorption studies, including equilibrium, kinetics and thermodynamic aspects, were performed. Kinetics was well described by the pseudo-first order model for TPC, and by a pseudo second-order kinetic model for ACs. TC adsorption equilibrium data were also fitted by different isotherm models: Langmuir, Freundlich, Sips, Dubinin Radushkevich, Dubinin-Astokov, Temkin, Redlich-Peterson, Radke-Prausnitz and Toth. The thermodynamic study confirmed that TC adsorption onto TPC-ACs is a spontaneous process. TC adsorption data obtained in the present study were compared with those reported in the literature, and differences were explained in terms of textural properties and surface functionalities. TPC-ACs had similar performances to those of commercial ACs, and might significantly improve the economic balance of the production of pyrolysis oil from waste tyres. PMID- 26855222 TI - Are insect repellents toxic to freshwater insects? A case study using caddisflies exposed to DEET. AB - Stream ecosystems face ever-increasing pressures by the presence of emergent contaminants, such as, personal care products. N, N-diethyl-3-methylbenzamide (DEET) is a synthetic insect repellent that is being found in surface waters environments in concentrations up to 33.4 MUg/L. Information concerning DEET's toxicity in the aquatic environment is still limited and focused only on its acute effects on model species. Our main objective was to assess the effects of DEET exposure to a caddisfly non-target species using sub-lethal endpoints. For that, we chose Sericostoma vittatum, an important shredder in Portuguese freshwaters that has been already used in different ecotoxicological assays. Besides acute tests, S. vittatum were exposed during 6 days to a gradient of DEET concentrations (8, 18 and 40.5 mg/L) to assess effects on feeding behaviour and biochemical responses, such as, lipid peroxidation levels (LPO), catalase and acetylcholinesterase (AChE) activities, and also assess effects on energy reserves and consumption. Acute tests revealed a 48 h-LC50 of 80.12 mg/L and DEET exposure caused feeding inhibition with a LOEC of 36.80 mg/L. Concerning the biochemical responses, DEET caused no effects in LPO nor on catalase activity. A non-significant decrease in AChE activity was observed. Regarding energetic reserves, exposure to DEET caused a significant reduction in S. vittatum carbohydrates levels. These results add important information for the risk assessment of insect repellents in the aquatic environment and suggest that reported environmental concentrations of DEET are not toxic to non-target freshwater insects. PMID- 26855223 TI - Biodegradation of persistent organics can overcome adsorption-desorption hysteresis in biological activated carbon systems. AB - In Biological Activated Carbon (BAC) systems, persistent organic pollutants can be removed through a combination of adsorption, desorption and biodegradation. These processes might be affected by the presence of other organics, especially by the more abundant easily-biodegradable organics, like acetate. In this research these relations are quantified for the removal of the persistent pharmaceutical metoprolol. Acetate did not affect the adsorption and desorption of metoprolol, but it did greatly enhance the metoprolol biodegradation. At least part of the BAC biomass growing on acetate was also able to metabolise metoprolol, although metoprolol was only converted after the acetate was depleted. The presence of easily-degradable organics like acetate in the feeding water is therefore beneficial for the removal of metoprolol in BAC systems. The isotherms obtained from metoprolol adsorption and desorption experiments showed that BAC systems are subject to hysteresis; for AC bioregeneration to take place the microbial biomass has to reduce the concentration at the AC-biomass interface 2.7 times compared to the concentration at which the carbon was being loaded. However, given the threshold concentration of the MET degrading microorganisms (<0.08 MUg/L) versus the average influent concentration (1.3 MUg/L), bioregeneration is feasible. PMID- 26855225 TI - Bisphenol A disrupts microtubules and induces multipolar spindles in dividing root tip cells of the gymnosperm Abies cephalonica. AB - The effects of bisphenol A (BPA), an endocrine chemical disruptor extensively used in the plastic and epoxy resin industry, on dividing root tip cells of the gymnosperm Abies cephalonica Loudon were investigated by confocal laser scanning microscopy after tubulin and endoplasmic reticulum immunolocalization and DNA staining. Microtubule arrays of all mitotic stages were disrupted within a few hours of treatment: preprophase bands exhibited asymmetric width; prometaphase, metaphase and anaphase spindles appeared sharply pointed, sigmoid or multipolar; phragmoplast microtubules were elongated and occasionally bended toward the daughter nuclei. Depending on the mitotic stage, the chromosomes appeared condensed at prophase, as a compact mass at metaphase and anaphase, unsegregated or bridged at telophase. Endoplasmic reticulum patterns were also affected, reflecting those of the respective microtubule arrays. Recovery of the microtubules after oryzalin treatment was more effective in a BPA solution than in water. It is concluded that the plant mitotic apparatus microtubules are very sensitive to BPA, the effect of which depends on the specific cell cycle stage. The formation of multipolar spindles is reminiscent of animal cells and is ascribed to the induction of multiple microtubule nucleation sites, deriving from the centrosomal properties of gymnosperms. PMID- 26855226 TI - Biomonitoring of atmospheric pollution by moss bags: Discriminating urban-rural structure in a fragmented landscape. AB - In this paper we investigated the possibility to use moss bags to detect pollution inputs - metals, metalloids and polycyclic aromatic hydrocarbons (PAHs) - in sites chosen for their different land use (agricultural, urban/residential scenarios) and proximity to roads (sub-scenarios), in a fragmented conurbation of Campania (southern Italy). We focused on thirty-nine elements including rare earths. For most of them, moss uptake was higher in agricultural than in urban scenarios and in front road sites. Twenty PAHs were analyzed in a subset of agricultural sites; 4- and 5-ringed PAHs were the most abundant, particularly chrysene, fluoranthene and pyrene. Overall results indicated that investigated pollutants have a similar spatial distribution pattern over the entire study area, with road traffic and agricultural practices as the major diffuse pollution sources. Moss bags proved a very sensitive tool, able to discriminate between different land use scenarios and proximity to roads in a mixed rural-urban landscape. PMID- 26855224 TI - Menstrual cycle perturbation by organohalogens and elements in the Cree of James Bay, Canada. AB - Persistent organohalogens (POHs) and metals have been linked to alterations in menstrual cycle function and fertility in humans. The Cree First Nations people living near James Bay in Ontario and Quebec, Canada, have elevated levels of POHs, mercury and lead compared to other Canadians. The present study examines the interrelationships between selected POHs and elements on menstrual cycle function in these Cree women. Menstrual cycle characteristics were derived from structured daily diaries and endocrine measurements from daily urine samples collected during one cycle for 42 women age 19-42. We measured 31 POHs in blood plasma and 18 elements in whole blood, for 31 of the participants. POHs and elements detected in >= 70% of the participants were transformed by principal component (PC) analysis to reduce the contaminant exposure data to fewer, uncorrelated PCA variables. Multiple regression analysis revealed that, after adjusting for confounders, PC-3 values showed significant negative association with cycle length, after adjusting for confounders (p = 0.002). PC-3 accounted for 9.2% of the variance and shows positive loadings for cadmium, selenium, and PBDE congeners 47 and 153, and a negative loading for copper. Sensitivity analysis of the model to quantify likely effect sizes showed a range of menstrual cycle length from 25.3 to 28.3 days using the lower and upper 95% confidence limits of mean measured contaminant concentrations to predict cycle length. Our observations support the hypothesis that the menstrual cycle function of these women may be altered by exposure to POHs and elements from their environment. PMID- 26855227 TI - Electrochemical mineralization pathway of quinoline by boron-doped diamond anodes. AB - Boron-doped diamond anodes were selected for quinoline mineralization, and the resulting intermediates, phenylpropyl aldehyde, phenylpropionic acid, and nonanal were identified and followed during quinoline oxidation by gas chromatography mass spectrometry and high-performance liquid chromatography. The evolutions of formic acid, acetic acid, oxalic acid, NO2(-), NO3(-), and NH4(+) were quantified. A new reaction pathway for quinoline mineralization by boron-doped diamond anodes has been proposed, where the pyridine ring in quinoline is cleaved by a hydroxyl radical giving phenylpropyl aldehyde and NH4(+). Phenylpropyl aldehyde is quickly oxidized into phenylpropionic acid, and the benzene ring is cleaved giving nonanal. This is further oxidized to formic acid, acetic acid, and oxalic acid. Finally, these organic intermediates are mineralized to CO2 and H2O. NH4(+) is also oxidized to NO2(-) and on to NO3(-). The results will help to gain basic reference for clearing intermediates and their toxicity. PMID- 26855228 TI - A Meta-Analysis of Hypnotherapeutic Techniques in the Treatment of PTSD Symptoms. AB - The efficacy of hypnotherapeutic techniques as treatment for symptoms of posttraumatic stress disorder (PTSD) was explored through meta-analytic methods. Studies were selected through a search of 29 databases. Altogether, 81 studies discussing hypnotherapy and PTSD were reviewed for inclusion criteria. The outcomes of 6 studies representing 391 participants were analyzed using meta analysis. Evaluation of effect sizes related to avoidance and intrusion, in addition to overall PTSD symptoms after hypnotherapy treatment, revealed that all studies showed that hypnotherapy had a positive effect on PTSD symptoms. The overall Cohen's d was large (-1.18) and statistically significant (p < .001). Effect sizes varied based on study quality; however, they were large and statistically significant. Using the classic fail-safe N to assess for publication bias, it was determined it would take 290 nonsignificant studies to nullify these findings. PMID- 26855229 TI - Colchicine Treatment for Tracheobronchial Amyloidosis. AB - Tracheobronchial amyloidosis is an infrequent disease characterized by the deposition of proteinaceous material in the tracheobronchial tree. The disease generally has a high morbidity and variable mortality in the years following diagnosis. There is no consensus on the optimal treatment. We report a case of a 63-year-old woman who presented with a diffuse tracheobronchial amyloidosis associated with laryngeal involvement, which required a percutaneous tracheostomy due to high-grade subglottic stenosis, with no evidence of systemic amyloidosis. After treatment exclusively with colchicine, she had a complete resolution of the stenotic area, with a very good response from the tracheobronchial amyloidosis disease, with only minor yellow plaques persisting. The patient has remained asymptomatic in the next 4 years of follow-up, with no evidence of endoscopic progression. This is the first documented case of this kind of response of tracheobronchial amyloidosis to colchicine treatment alone. A review of the available literature is presented. PMID- 26855230 TI - Application of Solid-State NMR Relaxometry for Characterization and Formulation Optimization of Grinding-Induced Drug Nanoparticle. AB - The formation mechanism of drug nanoparticles was investigated using solid-state nuclear magnetic resonance (NMR) techniques for the efficient discovery of an optimized nanoparticle formulation. The cogrinding of nifedipine (NIF) with polymers, including hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP), and sodium dodecyl sulfate (SDS) was performed to prepare the NIF nanoparticle formulations. Then, solid-state NMR relaxometry was used for the nanometer-order characterization of NIF in the polymer matrix. Solid-state NMR measurements revealed that the crystal size of NIF was reduced to several tens of nanometers with amorphization of NIF by cogrinding with HPMC and SDS for 100 min. Similarly, the size of the NIF crystal was reduced to less than 90 nm in the 40 min ground mixture of NIF/PVP/SDS. Furthermore, 100 min grinding of NIF/PVP/SDS induced amorphization of almost all the NIF crystals followed by nanosizing. The hydrogen bond between NIF and PVP led to the efficient amorphization of NIF in the NIF/PVP/SDS system compared with NIF/HPMC/SDS system. The efficient nanosizing of the NIF crystal in the solid state, revealed by the solid-state NMR relaxation time measurements, enabled the formation of large amounts of NIF nanoparticles in water followed by the polymer dissolution. In contrast, excess amorphization of the NIF crystals failed to efficiently prepare the NIF nanoparticles. The solid-state characterization of the crystalline NIF revealed good correlation with the NIF nanoparticles formation during aqueous dispersion. Furthermore, the solid-state NMR measurements including relaxometry successfully elucidated the nanometer-order dispersion state of NIF in polymer matrix, leading to the discovery of optimized conditions for the preparation of suitable drug nanoparticles. PMID- 26855232 TI - A depth-dependent profile of the lipid conformation and lateral packing order of the stratum corneum in vivo measured using Raman microscopy. AB - The intercellular lipid structure of the stratum corneum (SC) plays a key role in skin barrier function. A depth profile of the intercellular lipid conformation and the lipid lateral packing order were measured in vivo in the human SC using confocal Raman microscopy. The depth profiles of the 2880 cm(-1)/2850 cm(-1) peak ratio intensity, which represent the C-H stretching and lateral packing order of lipids, and the 1080 cm(-1)/(1130 cm(-1) + 1060 cm(-1)) peak ratio, which represents the C-C skeleton vibration and trans-gauche conformation order of lipids, were investigated. The influence of keratin on the lipid peaks at 2850 cm(-1) and 2880 cm(-1) was excluded by the developed mathematical algorithm. The results show that the trans-conformation and lateral packing order of the intercellular lipids reach their maximum value in the SC at 20-40% of its depth and then decrease towards the stratum granulosum. These results show that at a depth of 20-40% (normally corresponding to a depth of 4-8 MUm) the SC exhibits the most ordered lipids and therefore the highest skin barrier function. The lateral packing of lipids is more disordered on the surface and in the deeper parts of the SC, which may be associated with a reduced skin barrier function. PMID- 26855231 TI - Expanding role of gut microbiota in lipid metabolism. AB - PURPOSE OF REVIEW: This article highlights recent advances in the emerging role that gut microbiota play in modulating metabolic phenotypes, with a particular focus on lipid metabolism. RECENT FINDINGS: Accumulating data from both human and animal studies demonstrate that intestinal microbes can affect host lipid metabolism through multiple direct and indirect biological mechanisms. These include a variety of signaling molecules produced by gut bacteria that have potent effects on hepatic lipid and bile metabolism and on reverse cholesterol transport, energy expenditure, and insulin sensitivity in peripheral tissues. Additionally, host genetic factors can modulate the abundance of bacterial taxa, which can subsequently affect various metabolic phenotypes. Proof of causality for identified microbial associations with host lipid-related phenotypes has been demonstrated in several animal studies, but remains a challenge in humans. Ultimately, selective manipulation of the gut microbial ecosystem for intervention will first require a better understanding of which specific bacteria, or alternatively, which bacterial metabolites, are appropriate targets. SUMMARY: Recent discoveries have broad implications for elucidating bacterially mediated pathophysiological mechanisms that alter lipid metabolism and other related metabolic traits. From a clinical perspective, this newly recognized endocrine organ system can be targeted for therapeutic benefit of dyslipidemia and cardiometabolic diseases. PMID- 26855233 TI - So close yet so far: Motor anomalies impacting on social functioning in autism spectrum disorder. AB - Difficulties in the social domain and motor anomalies have been widely investigated in Autism Spectrum Disorder (ASD). However, they have been generally considered as independent, and therefore tackled separately. Recent advances in neuroscience have hypothesized that the cortical motor system can play a role not only as a controller of elementary physical features of movement, but also in a complex domain as social cognition. Here, going beyond previous studies on ASD that described difficulties in the motor and in the social domain separately, we focus on the impact of motor mechanisms anomalies on social functioning. We consider behavioral, electrophysiological and neuroimaging findings supporting the idea that motor cognition is a critical "intermediate phenotype" for ASD. Motor cognition anomalies in ASD affect the processes of extraction, codification and subsequent translation of "external" social information into the motor system. Intriguingly, this alternative "motor" approach to the social domain difficulties in ASD may be promising to bridge the gap between recent experimental findings and clinical practice, potentially leading to refined preventive approaches and successful treatments. PMID- 26855234 TI - Meta-analysis of molecular imaging of serotonin transporters in ecstasy/polydrug users. AB - We conducted a meta-analysis on the available data from studies investigating SERTs in ecstasy users and polydrug using controls. From 7 studies we compared data from 157 ecstasy users and 148 controls across 14 brain regions. The main effect suggested ecstasy/MDMA related SERT reductions (SMD=0.52, 95% CIs [0.40, 0.65]; Z=8.36, p<.01, I(2)=89%). A significant effect of subgroups (X(2)=37.41, df=13, p<.01, I(2)=65.3%) suggested differential effects across brain ROIs. Ecstasy users showed significant SERT reductions in 11 out of the 14 regions, including every neocortical and limbic region analysed. Greatest effects were observed in the occipital cortex (SMD=1.09, 95% CIs [0.70, 1.48]). No group effects were observed in subcortical areas of the caudate, putamen and midbrain. Literature on Postsynaptic 5HT2A receptor imaging was synthesised with these results. We conclude that, in line with preclinical data, serotonin axons with the longest projections from the raphe nuclei appear to be most affected by ecstasy/MDMA use. PMID- 26855235 TI - Brain glucose feedback predicts food choice (Commentary on Wakabayashi et al.). PMID- 26855236 TI - Large Size Hemicraniectomy Reduces Early Herniation in Malignant Middle Cerebral Artery Infarction. AB - BACKGROUND: Decompressive hemicraniectomy (DHC) reduces mortality and improves outcome after malignant middle cerebral artery infarction (MMI) but early in hospital mortality remains high between 22 and 33%. Possibly, this circumstance is driven by cerebral herniation due to space-occupying brain swelling despite decompressive surgery. As the size of the removed bone flap may vary considerably between surgeons, a size too small could foster herniation. Here, we investigated the effect of the additional volume created by an extended DHC (eDHC) on early in hospital mortality in patients suffering from MMI. METHODS: We performed a retrospective single-center cohort study of 97 patients with MMI that were treated either with eDHC (n = 40) or standard DHC (sDHC; n = 57) between January 2006 and June 2012. The primary study end point was defined as in-hospital mortality due to transtentorial herniation. RESULTS: In-hospital mortality due to transtentorial herniation was significantly lower after eDHC (0 vs. 11%; p = 0.04), which was paralleled by a significantly larger volume of the craniectomy (p < 0.001) and less cerebral swelling (eDHC 21% vs. sDHC 25%; p = 0.03). No statistically significant differences were found in surgical or non-surgical complications and postoperative intensive care treatment. CONCLUSION: Despite a more aggressive surgical approach, eDHC may reduce early in-hospital mortality and limit transtentorial herniation. Prospective studies are warranted to confirm our results and assess general safety of eDHC. PMID- 26855237 TI - Synthesis and Antiviral Activity Evaluation of 2',5',5'-Trifluoro-Apiosyl Nucleoside Phosphonic Acid Analogs. AB - Racemic synthesis of novel 2',5',5'-trifluoro-apiose nucleoside phosphonic acid analogs were performed as potent antiviral agents. Phosphonation was performed by direct displacement of triflate intermediate with diethyl (lithiodifluoromethyl) phosphonate to give the corresponding (alpha,alpha-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection of diethyl phosphonates provided the target nucleoside analogs. An antiviral evaluation of the synthesized compounds against various viruses such as HIV, HSV-1, HSV-2, and HCMV revealed that the pyrimidine analogues have significant anti-HCMV activity. PMID- 26855238 TI - The safety of treatments for prolactinomas. AB - INTRODUCTION: Prolactinomas are the most common hormone-secreting pituitary tumors, accounting for approximately 40% of all pituitary tumors. Infertility, gonadal and sexual dysfunction are usually the most relevant clinical features in both sexes. AREA COVERED: This review focuses on safety and tolerability of therapeutic approaches for prolactinomas. Complications from trans-sphenoidal surgery vary depending on tumor size, and mortality rate ranges 0.6%-31% for patients with microprolactinomas and macroprolactinoms, respectively. More than 50% of patients receiving pituitary radiotherapy will develop at least one hormone deficiency within the following decade, whereas cerebrovascular accidents, second brain tumors and optic neuropathy rarely occur. Nowadays, treatment of prolactinomas is based on dopamine-agonists (DA), mainly cabergoline (CAB). Whether CAB is associated with an increased risk of clinically relevant cardiac valvulopathy in patients with prolactinomas as in those with Parkinson's disease (PD), is still debated. In most studies, CAB has been found not to be associated with an increased risk of significant valvulopathy in prolactinomas, and no correlation has been shown between valvular abnormalities and CAB duration or cumulative dose. EXPERT OPINION: DA are safe and well tolerated, and the main safety concerns are related to the potential risk of clinically relevant valvulopathy following treatment with CAB, rarely occurring in patients with prolactinomas. PMID- 26855239 TI - Self-Organization of Microscale Condensate for Delayed Flooding of Nanostructured Superhydrophobic Surfaces. AB - Superhydrophobic surfaces enhance condensation by inhibiting the formation of an insulating liquid layer. While this produces efficient heat transfer at low supersaturations, superhydrophobicity has been shown to break down at increased supersaturations. As heat transfer increases, the random distribution and high density of nucleation sites produces pinned droplets, which lead to uncontrollable flooding. In this work, engineered variations in wettability are used to promote the self-organization of microscale droplets, which is shown to effectively delay flooding. Virus-templated superhydrophobic surfaces are patterned with an array of superhydrophilic islands designed to minimize surface adhesion while promoting spatial order. By use of optical and electron microscopy, the surfaces are optimized and characterized during condensation. Mixed wettability imparts spatial order not only through preferential nucleation but more importantly through the self-organization of coalescing droplets at high supersaturations. The self-organization of microscale droplets (diameters of <25 MUm) is shown to effectively delay flooding and govern the global wetting behavior of larger droplets (diameters of >1 mm) on the surface. As heat transfer increases, the surfaces transition from jumping-mode to shedding-mode removal with no flooding. This demonstrates the ability to engineer surfaces to resist flooding and can act as the basis for developing robust superhydrophobic surfaces for condensation applications. PMID- 26855240 TI - Identification of metabolic engineering targets for the enhancement of 1,4 butanediol production in recombinant E. coli using large-scale kinetic models. AB - Rational metabolic engineering methods are increasingly employed in designing the commercially viable processes for the production of chemicals relevant to pharmaceutical, biotechnology, and food and beverage industries. With the growing availability of omics data and of methodologies capable to integrate the available data into models, mathematical modeling and computational analysis are becoming important in designing recombinant cellular organisms and optimizing cell performance with respect to desired criteria. In this contribution, we used the computational framework ORACLE (Optimization and Risk Analysis of Complex Living Entities) to analyze the physiology of recombinant Escherichia coli producing 1,4-butanediol (BDO) and to identify potential strategies for improved production of BDO. The framework allowed us to integrate data across multiple levels and to construct a population of large-scale kinetic models despite the lack of available information about kinetic properties of every enzyme in the metabolic pathways. We analyzed these models and we found that the enzymes that primarily control the fluxes leading to BDO production are part of central glycolysis, the lower branch of tricarboxylic acid (TCA) cycle and the novel BDO production route. Interestingly, among the enzymes between the glucose uptake and the BDO pathway, the enzymes belonging to the lower branch of TCA cycle have been identified as the most important for improving BDO production and yield. We also quantified the effects of changes of the target enzymes on other intracellular states like energy charge, cofactor levels, redox state, cellular growth, and byproduct formation. Independent earlier experiments on this strain confirmed that the computationally obtained conclusions are consistent with the experimentally tested designs, and the findings of the present studies can provide guidance for future work on strain improvement. Overall, these studies demonstrate the potential and effectiveness of ORACLE for the accelerated design of microbial cell factories. PMID- 26855241 TI - Exudative Retinal Detachment Reveals Metastatic Bladder Cancer. AB - PURPOSE: Choroidal metastasis from bladder cancer is very rare, with only a handful of cases cited previously in the literature. We present a case of a patient who presented with a serous retinal detachment and a known history of bladder cancer, which he believed was controlled. Based on the clinical evaluation, his history of bladder cancer, and a retinal consult, a workup was initiated and he was found to have choroidal metastasis from his cancer. CASE REPORT: A 77-year-old white man presented with a 1-week history of blurry vision in his left eye and left-sided frontal headaches. His medical history was significant for medically managed hypertension and controlled bladder cancer, which had been treated with transurethral resection of bladder tumor and Bacillus Calmette-Guerin intravesical treatments. The patient had been a smoker for 35 years but had quit 22 years before presentation. A dilated retinal examination found an inferior serous retinal detachment in the left eye, with areas of subretinal folds and fluid encroaching on the macula on both clinical examination and optical coherence tomography imaging. The patient was diagnosed as having an exudative retinal detachment in his left eye, and he was referred for a retinal consult. Subsequent testing with B-scan and fluorescein angiography was suggestive of metastasis as the cause of the exudative detachment. Based on his history of bladder cancer, a chest X-ray was ordered and revealed a left-sided pleural effusion. A chest computed tomography confirmed the left pleural effusion and better visualized its extent. A thoracentesis with cytology supported the diagnosis of metastases from urothelial carcinoma. The patient's bladder cancer was now classified as stage 4, and he died 2 months later. CONCLUSIONS: This case highlights a rare instance of a choroidal metastasis from bladder cancer. As with previous cases, this is a poor prognostic sign for the patient's survival, and he died shortly after the discovery of the lesion. It is important to consider cancer metastasis in the differential diagnosis when presented with a serous retinal detachment and a known cancer diagnosis, even if the patient believes that his cancer is well managed. PMID- 26855242 TI - ADHD and Vision Problems in the National Survey of Children's Health. AB - PURPOSE: To compare the prevalence of attention deficit/hyperactivity disorder (ADHD) in children with normal vision and with vision problems not correctable with glasses or contact lenses (vision problems) as determined by parent report in a nationwide telephone survey. METHODS: This cross-sectional study included 75,171 children without intellectual impairment aged 4 to 17 years participating in the 2011 to 2012 National Survey of Children's Health, conducted by the U.S. Centers for Disease Control and Prevention. Demographic information and information regarding vision and ADHD status were obtained by parent interview. Questions asked whether they had ever been told by a doctor or health care provider that the child had a vision problem not correctable with glasses or contact lenses, ADHD, intellectual impairment, or one of 13 other common chronic conditions of childhood. A follow-up question asked about condition severity. The main outcome measure was current ADHD. RESULTS: The prevalence of current ADHD was greater (p < 0.0001) among children with vision problems (15.6%) compared with those with normal vision (8.3%). The odds of ADHD compared with those of children with normal vision were greatest for those with moderate vision problems (odds ratio [OR], 2.6; 95% confidence interval [95% CI], 1.7 to 4.4) and mild vision problems (OR, 1.8; 95% CI, 1.1 to 2.9). Children with severe vision problems had similar odds of ADHD to those of children with normal vision perhaps because of the small numbers in this group (OR, 1.6; 95% CI, 0.8 to 3.1). In multivariable analysis adjusting for confounding variables, vision problems remained independently associated with current ADHD (OR, 1.8; 95% CI, 1.2 to 2.7). CONCLUSIONS: In this large nationally representative sample, the prevalence of ADHD was greater among children with vision problems not correctable with glasses or contacts. The association between vision problems and ADHD remains even after adjusting for other factors known to be associated with ADHD. PMID- 26855243 TI - A Novel Marking Reader for Progressive Addition Lenses Based on Gabor Holography. AB - PURPOSE: Progressive addition lenses (PALs) are marked with permanent engraved marks (PEMs) at standardized locations. Permanent engraved marks are very useful through the manufacturing and mounting processes, act as locator marks to re-ink the removable marks, and contain useful information about the PAL. However, PEMs are often faint and weak, obscured by scratches, partially occluded, and difficult to recognize on tinted lenses or with antireflection or scratch resistant coatings. The aim of this article is to present a new generation of portable marking reader based on an extremely simplified concept for visualization and identification of PEMs in PALs. METHODS: Permanent engraved marks on different PALs are visualized using classical Gabor holography as underlying principle. Gabor holography allows phase sample visualization with adjustable magnification and can be implemented in either classical or digital versions. Here, visual Gabor holography is used to provide a magnified defocused image of the PEMs onto a translucent visualization screen where the PEM is clearly identified. RESULTS: Different types of PALs (conventional, personalized, old and scratched, sunglasses, etc.) have been tested to visualize PEMs with the proposed marking reader. The PEMs are visible in every case, and variable magnification factor can be achieved simply moving up and down the PAL in the instrument. In addition, a second illumination wavelength is also tested, showing the applicability of this novel marking reader for different illuminations. CONCLUSIONS: A new concept of marking reader ophthalmic instrument has been presented and validated in the laboratory. The configuration involves only a commercial-grade laser diode and a visualization screen for PEM identification. The instrument is portable, economic, and easy to use, and it can be used for identifying patient's current PAL model and for marking removable PALs again or finding test points regardless of the age of the PAL, its scratches, tints, or coatings. PMID- 26855244 TI - Dysgenetic polycystic disease of the minor and submandibular salivary glands. AB - BACKGROUND: Dysgenetic polycystic salivary gland disease is a rare pathology. No case of minor salivary gland involvement has been reported in the literature. METHODS: A female patient presented with bilateral tumors of the parotid glands, bilateral submandibular gland enlargement, and multiple cystic lesions of the oral mucosa. MRI of the neck was performed along with fine-needle aspiration (FNA) of the parotid tumors and excisional biopsy of an oral lesion. RESULTS: Imaging and FNA findings of the parotid glands were suggestive of bilateral Warthin tumors. Excisional biopsy of the oral lesion revealed a minor salivary gland with histopathological features of dysgenetic polycystic salivary gland disease. Submandibular gland enlargement was also attributed to this rare entity based on the imaging characteristics. CONCLUSION: This is the first report of dysgenetic polycystic salivary gland disease of the minor salivary glands, combined with involvement of the submandibular glands and bilateral Warthin tumors of the parotid gland. (c) 2016 Wiley Periodicals, Inc. Head Neck 38: E2437 E2439, 2016. PMID- 26855245 TI - Critical Review: What Dose of Rifabutin Is Recommended With Antiretroviral Therapy? AB - Since the advent of combination antiretroviral therapy to successfully treat HIV infection, drug-drug interactions (DDIs) have become a significant problem as many antiretrovirals (ARVs) are metabolized in the liver. Antituberculous therapy traditionally includes rifamycins, particularly rifampicin. Rifabutin (RBT) has shown similar efficacy as rifampicin but induces CYP3A4 to a lesser degree and is less likely to have DDIs with ARVs. We identified 14 DDI pharmacokinetic studies on HIV monoinfected and HIV-tuberculosis coinfected individuals, and the remaining studies were healthy volunteer studies. Although RBT may be coadministered with most nonnucleoside reverse transcriptase inhibitors, identifying the optimal dose with ritonavir-boosted or cobicistat-boosted protease inhibitors is challenging because of concern about adverse effects with increased RBT exposure. Limited healthy volunteer studies on other ARV drug classes and RBT suggest that dose modification may be unnecessary. The paucity of data assessing clinical tuberculosis endpoints concurrently with RBT and ARV pharmacokinetics limits evidence-based recommendations on the optimal dose of RBT within available ARV drug classes. PMID- 26855247 TI - Low Receipt and Uptake of Safer Conception Messages in Routine HIV Care: Findings From a Prospective Cohort of Women Living With HIV in South Africa. AB - BACKGROUND: Safer conception strategies may be used by people living with HIV to reduce HIV transmission to partners resulting from condomless sex for conception. The extent to which people living with HIV receive safer conception messages and use risk reduction strategies is largely unknown. METHODS: We use prospective data from a clinic-based cohort study in Johannesburg, South Africa. Women living with HIV (WLWH) aged 18-35 on antiretroviral therapy (n = 831) completed a baseline survey and >=1 follow-up visits assessing fertility intentions and pregnancy incidence; an endline survey was administered 1 year postenrollment. Multivariate negative binomial regression models examined differences in the number of condomless sex acts by fertility intentions. Chi-squared statistics compared receipt of safer conception messages by fertility intentions and indicators of safer conception method use by partner HIV status. RESULTS: The median baseline age of participants was 30.4 years and 25.3% were in serodiscordant partnerships. WLWH trying to conceive were over 3 times more likely to have condomless sex compared with those not trying to conceive (adjusted incidence rate ratio: 3.17, 95% confidence interval: 1.95 to 5.16). Receipt of specific safer conception messages was low, although women with positive fertility intentions were more likely to have received any fertility related advice compared with those with unplanned pregnancies (76.3% vs. 49.1%, P < 0.001). Among WLWH trying to conceive (n = 111), use of timed unprotected intercourse was infrequent (17.1%) and lower in serodiscordant vs. concordant partnerships (8.5% vs. 26.9%, P = 0.010). CONCLUSIONS: These findings suggest that clinic and patient-level interventions are needed to ensure that WLWH receive and use safer conception strategies. PMID- 26855248 TI - Response to Therapy in Antiretroviral Therapy-Naive Patients With Isolated Nonnucleoside Reverse Transcriptase Inhibitor-Associated Transmitted Drug Resistance. AB - BACKGROUND: Nonnucleoside reverse transcriptase inhibitor (NNRTI)-associated transmitted drug resistance (TDR) is the most common type of TDR. Few data guide the selection of antiretroviral therapy (ART) for patients with such resistance. METHODS: We reviewed treatment outcomes in a cohort of HIV-1-infected patients with isolated NNRTI TDR who initiated ART between April 2002 and May 2014. In an as-treated analysis, virological failure (VF) was defined as not reaching undetectable virus levels within 24 weeks, virological rebound, or switching regimens during viremia. In an intention-to-treat analysis, failure was defined more broadly as VF, loss to follow-up, and switching during virological suppression. RESULTS: Of 3245 patients, 131 (4.0%) had isolated NNRTI TDR; 122 received a standard regimen comprising 2 NRTIs plus a boosted protease inhibitor (bPI; n = 54), an integrase strand transfer inhibitor (INSTI; n = 52), or an NNRTI (n = 16). The median follow-up was 100 weeks. In the as-treated analysis, VF occurred in 15% (n = 8), 2% (n = 1), and 25% (n = 4) of patients in the bPI, INSTI, and NNRTI groups, respectively. In multivariate regression, there was a trend toward a lower risk of VF with INSTIs than with bPIs (hazard ratio: 0.14; 95% confidence interval: 0.02 to 1.1; P = 0.07). In intention-to-treat multivariate regression, INSTIs had a lower risk of failure than bPIs (hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.82; P = 0.01). CONCLUSIONS: Patients with isolated NNRTI TDR experienced low VF rates with INSTIs and bPIs. INSTIs were noninferior to bPIs in an analysis of VF but superior to bPIs when frequency of switching and loss to follow-up were also considered. PMID- 26855249 TI - Hemostatic Techniques for Myomectomy: An Evidence-Based Approach. AB - Uterine leiomyomas are the most common benign gynecologic tumor. They are also a significant cause of morbidity, necessitating treatments ranging from hormonal suppression to surgical intervention. Myomectomy, the removal of these highly vascular tumors, offers significant quality of life and fertility-sparing benefit for patients affected by uterine leiomyomas but with a risk of substantial intraoperative blood loss. This risk of hemorrhage leads not only an increased transfusion rate but also he need for hysterectomy and other potential operative complications. Numerous medical and surgical techniques have been developed to minimize potentially significant blood loss during abdominal, laparoscopic, and robotic-assisted myomectomies. Combined with judicious preoperative assessment, these techniques substantially enhance patient safety during a myomectomy and outcomes during recovery. PMID- 26855250 TI - Early detection of type 2 diabetes mellitus and screening for retinopathy are associated with reduced prevalence and severity of retinopathy. AB - PURPOSE: To explore whether the prevalence and severity of retinopathy differ in diabetes cohorts diagnosed through screening as compared with conventional health care. METHODS: A total of 257 diabetes patients, 151 detected through screening and 106 through conventional clinical care, were included. Retinopathy was evaluated by fundus photography. The modified Airlie House adaptation of the Early Treatment Retinopathy Study protocol was used to grade the photographs. Averages of clinically collected fasting blood glucose (FBG), blood pressure and body mass index values were compiled from diabetes diagnosis until the eye examination. Blood chemistry, smoking habits and peripheral neuropathy were assessed at the time of the eye examination. RESULTS: Among the screening detected patients, 22% had retinopathy as compared to 51% among those clinically detected (p < 0.0001). In a multivariate analysis, patients with retinopathy were more likely to have increased average FBG (OR 1.42, 95% CI 1.19-1.70 per mmol/l) and peripheral neuropathy (OR 2.75, 95% CI 1.40-5.43), but less likely to have screening-detected diabetes (OR 0.31, 95% CI 0.17-0.57). Similar results were found using increasing severity grade of retinopathy as outcome. The cumulative retinopathy prevalence for the screening-detected diabetes cohort as compared with the clinically diagnosed cohort was significantly lower from 10 years' follow-up and onwards (p = 0.0002). CONCLUSIONS: Among patients with screening detected diabetes, the prevalence of retinopathy and increasing severity of retinopathy were significantly lower than among those who had their diabetes diagnosed through conventional care, even when other risk factors for retinopathy such as duration, hyperglycaemia and blood pressure were considered. Early detection of diabetes reduces prediagnostic time spent with hyperglycaemia. In combination with early and regular screening for retinopathy, more effective prevention against retinopathy can be provided. PMID- 26855251 TI - Microtube Light-Emitting Diode Arrays with Metal Cores. AB - We report the fabrication and characteristics of vertical microtube light emitting diode (LED) arrays with a metal core inside the devices. To make the LEDs, gallium nitride (GaN)/indium gallium nitride (In(x)Ga(1-x)N)/zinc oxide (ZnO) coaxial microtube LED arrays were grown on an n-GaN/c-aluminum oxide (Al2O3) substrate. The microtube LED arrays were then lifted-off the substrate by wet chemical etching of the sacrificial ZnO microtubes and the silicon dioxide (SiO2) layer. The chemically lifted-off LED layer was then transferred upside down on other supporting substrates. To create the metal cores, titanium/gold and indium tin oxide were deposited on the inner shells of the microtubes, forming n type electrodes inside the metal-cored LEDs. The characteristics of the resulting devices were determined by measuring electroluminescence and current-voltage characteristic curves. To gain insights into the current-spreading characteristics of the devices and understand how to make them more efficient, we modeled them computationally. PMID- 26855252 TI - Nonenzymatic Transglycosylation Reactions Induced by Roasting: New Insights from Models Mimicking Coffee Bean Regions with Distinct Polysaccharide Composition. AB - Three mixtures containing different molar proportions of (beta1->4)-D-mannotriose and (alpha1->5)-L-arabinotriose, oligosaccharides structurally related to coffee polysaccharides (galactomannans and arabinogalactans), were roasted at 200 degrees C for different periods. Electrospray ionization mass spectrometry (ESI MS) and tandem mass spectrometry (ESI-MS(n)) analyses of labeled ((18)O) and unlabeled samples allowed identification of not only nonhybrid oligosaccharides but also hybrid oligosaccharides composed of both hexose and pentose units. The identification of hybrid oligosaccharides allowed us to infer the occurrence of nonenzymatic transglycosylation reactions involving both oligosaccharides in the starting mixtures. Also, it was observed that using different proportions of the oligosaccharides in the starting mixtures and extents of thermal treatment led to a variation in the composition of the compounds formed. These results have led to the conclusion that, depending on the distribution of the polysaccharides in the bean cell walls and the roasting conditions, different nonhybrid and hybrid structures can be formed during coffee roasting. PMID- 26855253 TI - A Quantitative Toxicogenomics Assay for High-throughput and Mechanistic Genotoxicity Assessment and Screening of Environmental Pollutants. AB - The ecological and health concern of mutagenicity and carcinogenicity potentially associated with an overwhelmingly large and ever-increasing number of chemicals demands for cost-effective and feasible method for genotoxicity screening and risk assessment. This study proposed a genotoxicity assay using GFP-tagged yeast reporter strains, covering 38 selected protein biomarkers indicative of all the seven known DNA damage repair pathways. The assay was applied to assess four model genotoxic chemicals, eight environmental pollutants and four negative controls across six concentrations. Quantitative molecular genotoxicity end points were derived based on dose response modeling of a newly developed integrated molecular effect quantifier, Protein Effect Level Index (PELI). The molecular genotoxicity end points were consistent with multiple conventional in vitro genotoxicity assays, as well as with in vivo carcinogenicity assay results. Further more, the proposed genotoxicity end point PELI values quantitatively correlated with both comet assay in human cell and carcinogenicity potency assay in mice, providing promising evidence for linking the molecular disturbance measurements to adverse outcomes at a biological relevant level. In addition, the high-resolution DNA damaging repair pathway alternated protein expression profiles allowed for chemical clustering and classification. This toxicogenomics based assay presents a promising alternative for fast, efficient and mechanistic genotoxicity screening and assessment of drugs, foods, and environmental contaminants. PMID- 26855254 TI - Development of an acoustic filter for parametric loudspeaker using phononic crystals. AB - The spurious signal generated as a result of nonlinearity at the receiving system affects the measurement of the difference-frequency sound in the parametric loudspeaker, especially in the nearfield or near the beam axis. In this paper, an acoustic filter is designed using phononic crystals and its theoretical simulations are carried out by quasi-one- and two-dimensional models with Comsol Multiphysics. According to the simulated transmission loss (TL), an acoustic filter is prototyped consisting of 5*7 aluminum alloy cylinders and its performance is verified experimentally. There is good agreement with the simulation result for TL. After applying our proposed filter in the axial measurement of the parametric loudspeaker, a clear frequency dependence from parametric array effect is detected, which exhibits a good match with the well known theory described by the Gaussian-beam expansion technique. During the directivity measurement for the parametric loudspeaker, the proposed filter has also proved to be effective and is only needed for small angles. PMID- 26855255 TI - Depicting as a method of communication. AB - In everyday discourse, people describe and point at things, but they also depict things with their hands, arms, head, face, eyes, voice, and body, with and without props. Examples are iconic gestures, facial gestures, quotations of many kinds, full-scale demonstrations, and make-believe play. Depicting, it is argued, is a basic method of communication. It is on a par with describing and pointing, but it works by different principles. The proposal here, called staging theory, is that depictions are physical scenes that people stage for others to use in imagining the scenes they are depicting. Staging a scene is the same type of act that is used by children in make-believe play and by the cast and crew in stage plays. This theory accounts for a diverse set of features of everyday depictions. Although depictions are integral parts of everyday utterances, they are absent from standard models of language processing. To be complete, these models will have to account for depicting as well as describing and pointing. PMID- 26855257 TI - A novel method for quantifying similarities between oscillatory neural responses in wavelet time-frequency power profiles. AB - Quantifying similarities and differences between neural response patterns is an important step in understanding neural coding in sensory systems. It is difficult, however, to compare the degree of similarity among transient oscillatory responses. We developed a novel method of wavelet correlation analysis for quantifying similarity between transient oscillatory responses, and tested the method with olfactory cortical responses. In the anterior piriform cortex (aPC), the largest area of the primary olfactory cortex, odors induce inhibitory activities followed by transient oscillatory local field potentials (osci-LFPs). Qualitatively, the resulting time courses of osci-LFPs for identical odors were modestly different. We then compared several methods for quantifying the similarity between osci-LFPs for identical or different odors. Using fast Fourier transform band-pass filters, a conventional method demonstrated high correlations of the 0-2Hz components for both identical and different odors. None of the conventional methods tested demonstrated a clear correlation between osci LFPs. However, wavelet correlation analysis resolved a stimulus dependency of 2 45Hz osci-LFPs in the aPC output layer, and produced experience-dependent high correlations in the input layer between some of the identical or different odors. These results suggest that redundancy in the neural representation of sensory information may change in the aPC. This wavelet correlation analysis may be useful for quantifying the similarities of transient oscillatory neural responses. PMID- 26855256 TI - Brain stimulation: Neuromodulation as a potential treatment for motor recovery following traumatic brain injury. AB - There is growing evidence that electrical and magnetic brain stimulation can improve motor function and motor learning following brain damage. Rodent and primate studies have strongly demonstrated that combining cortical stimulation (CS) with skilled motor rehabilitative training enhances functional motor recovery following stroke. Brain stimulation following traumatic brain injury (TBI) is less well studied, but early pre-clinical and human pilot studies suggest that it is a promising treatment for TBI-induced motor impairments as well. This review will first discuss the evidence supporting brain stimulation efficacy derived from the stroke research field as proof of principle and then will review the few studies exploring neuromodulation in experimental TBI studies. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID- 26855259 TI - Functional attributes of evolutionary conserved Arg45 of Wolbachia (Brugia malayi) translation initiation factor-1. AB - AIM: Wolbachia is a promising antifilarial chemotherapeutic target. Translation initiation factor-1 (Tl IF-1) is an essential factor in prokaryotes. Functional characterization of Wolbachia's novel proteins/enzymes is necessary for the development of adulticidal drugs. MATERIALS & METHODS: Mutant, Wol Tl IF-1 R45D was constructed by site directed mutagenesis. Fluorimetry and size exclusion chromatography were used to determine the biophysical characteristics. Mobility shift assay and fluorescence resonance energy transfer were used to investigate the functional aspect of Wol Tl IF-1 with its mutant. RESULTS: Both wild and mutant were in monomeric native conformations. Wild exhibits nonspecific binding with ssRNA/ssDNA fragments under electrostatic conditions and showed annealing and displacement of RNA strands in comparison to mutant. CONCLUSION: Point mutation impaired RNA chaperone activity of the mutant and its interaction with nucleotides. PMID- 26855258 TI - Strategies targeting endogenous neurogenic cell response to improve recovery following traumatic brain injury. AB - Traumatic brain injury (TBI) affects over 1.7 million people in the United States alone and poses many clinical challenges due to the variability of the injuries and complexity of biochemical mechanisms involved. Thus far, there is still no effective therapy for TBI. Failure of preventative therapeutic strategies has led studies focusing on regenerative approaches. Recent studies have shown evidence that mature brains harbors multipotent neural stem cells capable of becoming mature neurons in the neurogenic regions. Following brain insults including TBI, the injured brain has increased level of neurogenic response in the subventricular zone and dentate gyrus of the hippocampus and this endogenous response is associated with cognitive function following injury. In this review, we highlight recent development and strategies aimed at targeting this endogenous cell response to enhance post-TBI functional recovery. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID- 26855261 TI - Insertable Fast-Response Amperometric NO/CO Dual Microsensor: Study of Neurovascular Coupling During Acutely Induced Seizures of Rat Brain Cortex. AB - This paper reports the fabrication of an insertable amperometric dual microsensor and its application for the simultaneous and fast sensing of NO and CO during acutely induced seizures of living rat brain cortex. NO and CO are important signaling mediators, controlling cerebrovascular tone. The dual NO/CO sensor is prepared based on a dual microelectrode having Au-deposited Pt microdisk (WE1, 76 MUm diameter) and Pt black-deposited Pt disk (WE2, 50 MUm diameter). The different deposited metals for WE1 and WE2 allow the selective anodic detection of CO at WE1 (+0.2 V vs Ag/AgCl) and that of NO at WE2 (+0.75 V vs Ag/AgCl) with sufficient sensitivity. Fluorinated xerogel coating on this dual electrode provides exclusive selectivity over common biological interferents, along with fast response time. The miniaturized size (end plane diameter < 300 MUm) and tapered needle-like sensor geometry make the sensor become insertable into biological tissues. The sensor is applied to simultaneously monitor dynamic changes of NO and CO levels in a living rat brain under acute seizure condition induced by 4-aminopyridine in cortical tissue near the area of seizure induction. In-tissue measurement shows clearly defined patterns of NO/CO changes, directly correlated with observed LFP signal. Current study verifies the feasibility of a newly developed NO/CO dual sensor for real-time fast monitoring of intimately connected NO and CO dynamics. PMID- 26855262 TI - Investigating the efficacy of a whole team, psychologically informed, acute mental health service approach. AB - BACKGROUND: Service user demand and service changes, from hospital based, to community and hospital mix, within acute adult mental health services, focus the need for psychologically informed, holistic, approaches. AIMS: (1) Describe and report feasibility of a psychologically led Intensive Support Programme (ISP) to meet this need. (2) Present results of a pilot evaluation of this programme. METHOD: ISP was implemented in four acute mental health services of the Southern Health NHS Trust, available to both inpatient and outpatient acute services. Evaluation of the service one month after data collection, illustrates operation and level of uptake across different professional roles. The programme was evaluated by assessing psychological distress (CORE-10) and confidence in self management (Mental Health Confidence Scale) of participating service users before and after intervention. RESULTS: The service evaluation demonstrated extensive roll out of this programme across acute services of an extensive NHS Trust. Repeated measure t-tests demonstrated significant decrease in distress (p < 0.0005) and significant increase in confidence in self-management of mental health (p < 0.0005). CONCLUSION: Evaluation shows that ISP can be delivered in routine care in an acute mental health service and results in improvement in self management skills and facilitation of recovery. PMID- 26855263 TI - Nickel-Catalyzed Hydroacylation of Styrenes with Simple Aldehydes: Reaction Development and Mechanistic Insights. AB - The first nickel-catalyzed intermolecular hydroacylation reaction of alkenes with simple aldehydes has been developed. This reaction offers a new approach to the selective preparation of branched ketones in high yields (up to 99%) and branched selectivities (up to 99:1). Experimental data provide evidence for reversible formation of acyl-nickel-alkyl intermediate, and DFT calculations show that the aldehyde C-H bond transfer to a coordinated alkene without oxidative addition is involved. The origin of the reactivity and regioselectivity of this reaction was also investigated computationally, which are consistent with experimental observations. PMID- 26855260 TI - How retrotransposons shape genome regulation. AB - Retrotransposons are mutagenic units able to move within the genome. Despite many defenses deployed by the host to suppress potentially harmful activities of retrotransposons, these genetic units have found ways to meld with normal cellular functions through processes of exaptation and domestication. The same host mechanisms targeting transposon mobility allow for expansion and rewiring of gene regulatory networks on an evolutionary time scale. Recent works demonstrating retrotransposon activity during development, cell differentiation and neurogenesis shed new light on unexpected activities of transposable elements. Moreover, new technological advances illuminated subtler nuances of the complex relationship between retrotransposons and the host genome, clarifying the role of retroelements in evolution, development and impact on human disease. PMID- 26855264 TI - Corrigendum: Green synthesis of carbon-supported nanoparticle catalysts by physical vapor deposition on soluble powder substrates. PMID- 26855265 TI - Catalytic repertoire of bacterial bisindole formation. AB - Bacterial bisindole alkaloids that derive from the oxidative dimerization of l tryptophan possess diversified biological activities and unique molecular structures. In recent years, the number of bisindoles and their gene clusters has greatly expanded, revealing a large genetic toolbox for the generation of unique structural modifications. In this review, we will discuss the enzymatic pathways leading to diverse bisindoles structures. We will focus on the discovery of molecules through metagenomic mining, the elucidation of new enzymatic mechanisms, and the identification of new biosynthetic protecting group strategies. We will also highlight the newest work in combinatorial engineering and synthetic biology. PMID- 26855266 TI - Within- and between-session replicability of cognitive brain processes: An MEG study with an N-back task. AB - In the vast majority of electrophysiological studies on cognition, participants are only measured once during a single experimental session. The dearth of studies on test-retest reliability in magnetoencephalography (MEG) within and across experimental sessions is a preventing factor for longitudinal designs, imaging genetics studies, and clinical applications. From the recorded signals, it is not straightforward to draw robust and steady indices of brain activity that could directly be used in exploring behavioral effects or genetic associations. To study the variations in markers associated with cognitive functions, we extracted three event-related field (ERF) features from time-locked global field power (GFP) epochs using MEG while participants were performing a numerical N-back task in four consecutive measurements conducted during two different days separated by two weeks. We demonstrate that the latency of the M170, a neural correlate associated with cognitive functions such as working memory, was a stable parameter and did not show significant variations over time. In addition, the M170 peak amplitude and the mean amplitude of late positive component (LPP) also expressed moderate-to-strong reliability across multiple measures over time over many sensor spaces and between participants. The M170 amplitude varied more significantly between the measurements in some conditions but showed consistency over the participants over time. In addition we demonstrated significant correlation with the M170 and LPP parameters and cognitive load. The results are in line with the literature showing less within subject fluctuation for the latency parameters and more consistency in between subject comparisons for amplitude based features. The within-subject consistency was apparent also with longer delays between the measurements. We suggest that with a few limitations the ERF features show sufficient reliability and stability for longitudinal research designs and clinical applications for cognitive functions in single as well as cross-subject designs. PMID- 26855267 TI - Effects of caffeinated chewing gum on muscle pain during submaximal isometric exercise in individuals with fibromyalgia. AB - Physical activity is important to manage symptom of fibromyalgia (FM); however, individuals with FM typically experience augmented muscle pain during exercise. This study examined the effects of caffeinated chewing gum on exercise-induced muscle pain in individuals with FM. This study was conducted with a double-blind, placebo-controlled, cross-over design. Twenty-three patients with FM completed a caffeine condition where they consumed a caffeinated chewing gum that contains 100mg of caffeine, and a placebo condition where they consumed a non-caffeinated chewing gum. They completed isometric handgrip exercise at 25% of their maximal strength for 3 min, and muscle pain rating (MPR) was recorded every 30s during exercise. Clinical pain severity was assessed in each condition using a pain questionnaire. The order of the two conditions was randomly determined. MPR increased during exercise, but caffeinated chewing gum did not attenuate the increase in MPR compared to placebo gum. Clinical pain severity was generally associated with the average MPR and the caffeine effects on MPR, calculated as difference in the average MPR between the two conditions. The results suggest that more symptomatic individuals with FM may experience greater exercise-induced muscle pain, but benefit more from caffeinated chewing gum to reduce exercise induced muscle pain. PMID- 26855268 TI - Feasibility and Reliability of Pediatric Early Warning Score in the Emergency Department. AB - Pediatric early warning scores in an emergency department may be used in routine patient evaluation of illness severity and resource allocation, thereby positively impacting quality and safety in pediatric care. This prospective nursing study assessed the feasibility and reliability of pediatric early warning scores in a busy, inner-city, level 1 trauma center pediatric emergency department. The pediatric early warning scores demonstrated high interrater reliability (degree of agreement among scorers) (intraclass correlation coefficient = 0.91) and intrarater reliability (multiple repetitions by a single scorer) (intraclass correlation coefficient = 0.90). PMID- 26855270 TI - Innovation in Health Informatics: much is underpinned by eHealth and better information for patients. AB - Health informatics is a relatively young discipline, bringing together professionals with a range of backgrounds, including management professionals, computer specialists and health care professionals. A lot of focus has been on developing systems such as medical records and information sharing, and it also has the potential to span the boundaries between health care professionals and patients. This is especially true for people living with a long-term condition. PMID- 26855269 TI - Inducible scAAV2.GRE.MMP1 lowers IOP long-term in a large animal model for steroid-induced glaucoma gene therapy. AB - Current treatment of glaucoma relies on administration of daily drops or eye surgery. A gene therapy approach to treat steroid-induced glaucoma would bring a resolution to millions of people worldwide who depend on glucocorticoid therapy for a myriad of inflammatory disorders. Previously, we had characterized a short term Adh.GRE.MMP1 gene vector for the production of steroid-induced MMP1 in the trabecular meshwork and tested reduction of elevated intraocular pressure (IOP) in a sheep model. Here we conducted a trial transferring the same transgene cassette to a clinically safe vector (scAAV2), and extended the therapeutic outcome to longer periods of times. No evidence of ocular and/or systemic toxicity was observed. Viral genome distributions showed potential reinducible vector DNAs in the trabecular meshwork (0.4 v.g. per cell) and negligible copies in six major internal organs (0.00002-0.005 v.g. per cell). Histological sections confirmed successful transduction of scAAV2.GFP to the trabecular meshwork. Optimization of the sheep steroid-induced hypertensive model revealed that topical ophthalmic drug difluprednate 0.05% (durezol) induced the highest IOP elevation in the shortest time. This is the first efficacy/toxicity study of a feasible gene therapy treatment of steroid-induced hypertension using clinically accepted self-complementary adeno-associated vectors (scAAV) vectors in a large animal model. PMID- 26855271 TI - Mobile health and Parkinson: what is the future? PMID- 26855272 TI - How Do Clinical Information Systems Affect the Cognitive Demands of General Practitioners?: Usability Study with a Focus on Cognitive Workload. AB - BACKGROUND: Clinical information systems in the National Health Service do not need to conform to any explicit usability requirements. Poor usability can increase the mental workload experienced by clinicians and cause fatigue, increase error rates and impact the overall patient safety. Mental workload can be used as a measure of usability. OBJECTIVE: To assess the subjective cognitive workload experienced by general practitioners (GPs) with their systems. To raise awareness of the importance of usability in system design among users, designers, developers and policymakers. METHOD: We used a modified version of the NASA Task Load Index, adapted for web. We developed a set of common clinical scenarios and computer tasks on an online survey. We emailed the study link to 199 clinical commissioning groups and 1,646 GP practices in England. RESULTS: Sixty-seven responders completed the survey. The respondents had spent an average of 17 years in general practice, had experience of using a mean of 1.5 GP computer systems and had used their current system for a mean time of 6.7 years. The mental workload score was not different among systems. There were significant differences among the task scores, but these differences were not specific to particular systems. The overall score and task scores were related to the length of experience with their present system. CONCLUSION: Four tasks imposed a higher mental workload on GPs: 'repeat prescribing', 'find episode', 'drug management' and 'overview records'. Further usability studies on GP systems should focus on these tasks. Users, policymakers, designers and developers should remain aware of the importance of usability in system design.What does this study add?* Current GP systems in England do not need to conform to explicit usability requirements. Poor usability can increase the mental workload of clinicians and lead to errors.* Some clinical computer tasks incur more cognitive workload than others and should be considered carefully during the design of a system.* GPs did not report overall very high levels of subjective cognitive workload when undertaking common clinical tasks with their systems.* Further usability studies on GP systems should focus on the tasks incurring higher cognitive workload.* Users, policymakers, and designers and developers should remain aware of the importance of usability in system design. PMID- 26855273 TI - What Does ePrescribing Mean for Patients? A Case Study of the Perspectives of Hospital Renal Patients. AB - BACKGROUND: Hospital ePrescribing systems are expected to improve quality of care for patients, yet the perspectives of patients themselves have seldom been explored in the context of ePrescribing deployments. OBJECTIVE: We sought to understand the significance of ePrescribing for patients through a case study of renal in-patients on a hospital ward, before and after the introduction of an ePrescribing system. METHODS: Three data sources were drawn on as part of the case study: interviews with representatives from national patient groups (n = 10), in-patients on a renal ward (n = 11 pre-implementation; n = 12 post implementation) and fieldnotes (n = 25) of observations made on the case study ward. Data were analysed thematically focusing on: (1) perceived benefits of ePrescribing; (2) patient awareness and understanding of the medications prescribed and (3) patient views on medicines reconciliation at admission and discharge. RESULTS: While ePrescribing was viewed positively overall, its implementation in the case study site failed to address the lack of patient involvement in the prescribing process and poor medication counselling upon discharge. Importantly, the limited impact of the ePrescribing system in these particular areas appeared to be the result of institutional and cultural practices rather than solely technological factors. CONCLUSIONS: The introduction of ePrescribing systems offers new opportunities to improve sharing of knowledge and communication with all those involved in the patient's care pathways, including patients, carers and healthcare professionals across diverse care settings. Achieving this will, first and foremost, require significant cultural and policy shifts in how the patient's role is perceived by clinicians in relation to medicines management. PMID- 26855274 TI - National Health Models and the Adoption of E-Health and E-Prescribing in Primary Care - New Evidence from Europe. AB - OBJECTIVE: Recent research from the European Commission (EC) suggests that the development and adoption of eHealth in primary care is significantly influenced by the context of the national health model in operation. This research identified three national health models in Europe at this time - the National Health Service (NHS) model, the social insurance system (SIS) model and the transition country (TC) model, and found a strong correlation between the NHS model and high adoption rates for eHealth. The objective of this study is to establish if there is a similar correlation in one specific application area - electronic prescribing (ePrescribing) in primary care. METHODS: A review of published literature from 2000 to 2014 was undertaken covering the relevant official publications of the European Union and national government as well as the academic literature. An analysis of the development and adoption of ePrescribing in Europe was extracted from these data. RESULTS: The adoption of ePrescribing in primary care has increased significantly in recent years and is now practised by approximately 32% of European general practitioners. National ePrescribing services are now firmly established in 11 countries, with pilot projects underway in most others. The highest adoption rates are in countries with the NHS model, concentrated in the Nordic area. The electronic transmission of prescriptions continues to pose a significant challenge, especially in SIS countries and TCs. CONCLUSIONS: There is a strong correlation between the NHS model and high adoption rates for ePrescribing similar to the EC findings on the adoption of eHealth. It may be some time before many SIS countries and TCs reach the same adoption levels for ePrescribing and eHealth in primary care as most NHS countries. PMID- 26855275 TI - "How long does it take?" A mixed methods evaluation of computer-related work in GP consultations. AB - BACKGROUND: Systematic reviews have suggested that time spent on computer-related tasks increases consultation length. However, these reviews pre-date the current ubiquitous use of computers in U.K. general practice. OBJECTIVE: As part of a U.K. national study of the influence of information technology (IT) on the interaction between patients and healthcare professionals during consultations, we explored how IT functions affected time allocation and styles of computer use during general practitioner (GP) consultations. METHODS: We drew on multichannel video recording of consultations and measured consultation phases and the duration of computer-related tasks. We related measures of actual time to GP's interpretation of computer use elicited in qualitative interviews. RESULTS: Our sample included recordings of 112 consultations from 6 GPs in three practices. The computer was used for about one-third of the greater consultation. However, its use was concentrated pre- and post- the patient consultation. The workflow of consultation was exemplified through six computer use cases. Most functionality was accepted and accommodated within the consultation, though disruptive and time consuming tasks were generally delegated to administrative staff. Recognised styles of computer use (minimal, block and conversational) were apparent, but applied very flexibly by GPs according to the nature of the consultation. CONCLUSIONS: In contrast to earlier reports, contemporary computer use does not appear to have lengthened consultations. GPs adopted different styles of computer use in different consultations, challenging classifications that seek to stereotype GP computer use. Designing systems that support this versatility require an understanding of the fluid application of computer use within consultation structure. PMID- 26855276 TI - Using routinely collected health data for surveillance, quality improvement and research: Framework and key questions to assess ethics, privacy and data access. AB - BACKGROUND: The use of health data for public health, surveillance, quality improvement and research is crucial to improve health systems and health care. However, bodies responsible for privacy and ethics often limit access to routinely collected health data. Ethical approvals, issues around protecting privacy and data access are often dealt with by different layers of regulations, making approval processes appear disjointed. OBJECTIVE: To create a comprehensive framework for defining the ethical and privacy status of a project and for providing guidance on data access. METHOD: The framework comprises principles and related questions. The core of the framework will be built using standard terminology definitions such as ethics-related controlled vocabularies and regional directives. It is built in this way to reduce ambiguity between different definitions. The framework is extensible: principles can be retired or added to, as can their related questions. Responses to these questions should allow data processors to define ethical issues, privacy risk and other unintended consequences. RESULTS: The framework contains three steps: (1) identifying possible ethical and privacy principles relevant to the project; (2) providing ethics and privacy guidance questions that inform the type of approval needed; and (3) assessing case-specific ethics and privacy issues. The outputs from this process should inform whether the balance between public interests and privacy breach and any ethical considerations are tipped in favour of societal benefits. If they are then this should be the basis on which data access is permitted. Tightly linking ethical principles to governance and data access may help maintain public trust. PMID- 26855277 TI - In this issue: An innovative discipline needs a patient focus. PMID- 26855279 TI - Rhodium-Catalyzed C-H Bond Functionalization with Amides by Double C-H/C-N Bond Activation. AB - The first C-H bond functionalization with amides as the coupling partners via selective activation of the amide N-C bond using rhodium(I) catalysts under highly chemoselective conditions is reported. Notably, this report constitutes the first catalytic activation of the amide N-C(O) bond by rhodium. We expect that this concept will have broad implications for using amides as coupling partners for C-H activation beyond the work described herein. PMID- 26855280 TI - Genetic Manipulation of Nocardia Species. AB - Nocardia spp. are aerobic, Gram-positive, catalase positive, and non-motile actinomycetes. They are associated with human infections. However, some species produce important natural products, degrade toxic chemicals, and are involved in biotransformation of valuable products. The lack of robust genetic tools has hindered detailed studies and advanced research. This unit describes the major genetic engineering approaches using Nocardia sp. CS682 as a prototype. These methods will certainly help in understanding the basis of their pathogenicity as well as biosynthetic and biotransforming abilities. It can be expected that knowledge of the biochemistry behind their pathogenicity will be crucial in developing effective treatment strategies. These genetic tools can be utilized to develop rational metabolic engineering approaches for crafting host strains with higher production or biotransformation ability. PMID- 26855278 TI - Severe Ocular Inflammation Following Ranibizumab or Aflibercept Injections for Age-Related Macular Degeneration: A Retrospective Claims Database Analysis. AB - PURPOSE: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents including ranibizumab and aflibercept are used to treat patients with ocular disorders such as neovascular age-related macular degeneration (nAMD); however, the injections are associated with rare instances of severe ocular inflammation. This study compared severe ocular inflammation rates in patients treated with ranibizumab versus aflibercept. METHODS: United States physician-level claims data covering an 18-month period for each therapy were analyzed. The primary analysis compared severe ocular inflammation event rates per 1000 injections. Sensitivity and subgroup analyses evaluated the impact of factors including intraocular surgery, intravitreal antibiotic administration, and previous intravitreal injections. RESULTS: The analysis included 432,794 injection claims (ranibizumab n = 253,647, aflibercept n = 179,147); significantly, more unique severe ocular inflammation events occurred in patients receiving aflibercept than ranibizumab (1.06/1000 injections, 95% confidence interval [CI], 0.91-1.21, vs. 0.64/1000 injections, 95% CI 0.54-0.74; p < 0.0001). Comparable results were observed for analyses of patients who had undergone glaucoma or cataract surgeries, had antibiotic-associated endophthalmitis, had non-antibiotic-associated endophthalmitis, and were non treatment-naive. In contrast, no significant differences in severe ocular inflammation claims were recorded in treatment-naive patients who had no record of anti-VEGF treatment in the 6 months preceding the index claim. No significant change occurred in the rate of severe ocular inflammation claims over time following ranibizumab treatment. CONCLUSIONS: Severe ocular inflammation was more frequent following intravitreal injection with aflibercept than with ranibizumab during routine clinical use in patients with nAMD. This highlights the importance of real-world, post-approval, observational monitoring of novel medicines, and may aid clinical decision-making, including choice of anti-VEGF agent. PMID- 26855281 TI - Construction of a Transcription Map for Papillomaviruses using RACE, RNase Protection, and Primer Extension Assays. AB - Papillomaviruses are a family of small, non-enveloped DNA tumor viruses. Knowing a complete transcription map of each papillomavirus genome can provide guidance for various papillomavirus studies. This unit provides detailed protocols to construct a transcription map of human papillomavirus type 18. The same approach can be easily adapted to other transcription map studies of any other papillomavirus genotype due to the high degree of conservation in genome structure, organization, and gene expression among papillomaviruses. The focused methods are 5'- and 3'-rapid amplification of cDNA ends (RACE), which are techniques commonly used in molecular biology to obtain full-length RNA transcript or to map a transcription start site (TSS) or an RNA polyadenylation (pA) cleavage site. Primer walking RT-PCR is a method for studying the splicing junction of RACE products. In addition, RNase protection assay and primer extension are also introduced as alternative methods in the mapping analysis. PMID- 26855282 TI - HT-SPOTi: A Rapid Drug Susceptibility Test (DST) to Evaluate Antibiotic Resistance Profiles and Novel Chemicals for Anti-Infective Drug Discovery. AB - Antibiotic resistance is one of the major threats to global health and well being. The past decade has seen an alarming rise in the evolution and spread of drug-resistant strains of pathogenic microbes. The emergence of extensively drug resistant (XDR) strains of Mycobacterium tuberculosis and antimicrobial resistance among the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species) as well as fungal pathogens (such as certain species of Candida, Aspergillus, Cryptococcus, and Trichophyton) poses a significant 21st century scientific challenge. With an extremely limited arsenal of efficacious antibiotics, techniques that can (a) identify novel antimicrobials and (b) detect antimicrobial resistance are becoming increasingly important. In this article, we illustrate the HT-SPOTi, an assay that is principally based on the growth of an organism on agar medium containing a range of different concentrations of drugs or inhibitors. The simple methodology makes this assay ideal for evaluating novel antimicrobial compounds as well as profiling an organism's antibiotic resistance profile. PMID- 26855283 TI - Investigation of Viral and Host Chromatin by ChIP-PCR or ChIP-Seq Analysis. AB - Complex regulation of viral transcription patterns and DNA replication levels is a feature of many DNA viruses. This is especially true for those viruses which establish latent or persistent infections (e.g., herpesviruses, papillomaviruses, polyomaviruses, or adenovirus), as long-term persistence often requires adaptation of gene expression programs and/or replication levels to the cellular milieu. A key factor in the control of such processes is the establishment of a specific chromatin state on promoters or replication origins, which in turn will determine whether or not the underlying DNA is accessible for other factors that mediate downstream processes. Chromatin immunoprecipitation (ChIP) is a powerful technique to investigate viral chromatin, in particular to study binding patterns of modified histones, transcription factors or other DNA-/chromatin-binding proteins that regulate the viral lifecycle. Here, we provide protocols that are suitable for performing ChIP-PCR and ChIP-Seq studies on chromatin of large and small viral genomes. PMID- 26855284 TI - Obtaining High Quality DNA from Diverse Clinical Samples. AB - Nucleic acids can be obtained in numerous ways from clinical specimens; however, the quality of the nucleic acid is only as good as the sampling and isolation protocol. While nucleic acids may be extracted they may not be representative of the original source. Large areas of tissue and explanted hardware must be successfully surveyed to reflect the overall clinical picture. Once good sampling technique has been established, successful bacterial nucleic acid isolation is essential. Clinical samples may be difficult to process because of the presence of scar tissue, bone, implants, and bacterial biofilms. The following protocols provide details on sampling techniques and DNA isolation from a variety of clinical samples which can then be used in downstream molecular applications including PCR-MS-ESI-TOF technology. PMID- 26855285 TI - A high throughput solubility assay for drug discovery using microscale shake flask and rapid UHPLC-UV-CLND quantification. AB - The rapid determination of key physical properties of lead compounds is essential to the drug discovery process. Solubility is one of the most important properties since good solubility is needed not only for obtaining reliable in vitro and in vivo assay results in early discovery but also to ensure sufficient concentration of the drug being in circulation to get the desired therapeutic exposure at the target of interest. In order for medicinal chemists to tune solubility of lead compounds, a rapid assay is needed to provide solubility data that is accurate and predictive so that it can be reliably used for designing the next generation of compounds with improved properties. To ensure speed and data quality, we developed a high throughput solubility assay that utilizes a single calibration UHPLC-UV-CLND method and a 24h shake-flask format for rapid quantification. A set of 46 model compounds was used to demonstrate that the method is accurate, reproducible and predictive. Here we present development of the assay, including evaluation of quantification method, filtration membranes, equilibrium times, DMSO concentrations, and buffer conditions. A comparison of thermodynamic solubility results to our high throughput 24h shake-flask solubility assay results is also discussed. PMID- 26855286 TI - Development and validation of a UPLC-MS/MS method for the novel folate-targeted small molecule drug conjugate EC1456 and its metabolites in tumor homogenates from mice. AB - EC1456 is a novel folate-targeted small molecule drug conjugate of tubulysin B hydrazide being developed as an anticancer agent for patients with advanced solid tumors expressing the folate receptor. To try and correlate circulating systemic levels of EC1456 and its metabolites to tumor concentrations and potentially develop a PK/PD model, a sensitive bioanalytical method was developed and validated for the quantitation of the analytes in KB tumor homogenates. The method involved homogenizing tumors with buffer containing N-maleoyl-beta alanine, mannitol and acetic acid, precipitation of the homogenate with acetone followed by heating at 55 degrees C for 1h to convert tubulysin B hydrazide to its corresponding hydrazone. The extracts were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The method demonstrated good inter-day (3 runs, n=18) accuracy (-2.3% to 7.3%) and precision (1.7% to 10.3%) for all three analytes. Stability was established for three freeze-thaw cycles, 4h on the bench top on ice, 20h in the autosampler at 8 degrees C and for at least 46days frozen at -70 degrees C. This method was successfully used to determine concentration of EC1456 and its metabolites tubulysin B hydrazide and tubulysin B in tumor homogenates in preliminary experiments with KB tumor bearing mice dosed intravenously with EC1456. PMID- 26855288 TI - Prevention of Surgical Site Infections in Joint Replacement Surgery. AB - Prosthetic joint infections (PJI), although rare, represent a serious complication of total joint arthroplasty as they pose not only a direct financial burden to the patient but also an indirect burden related to psychosocial impact that PJI incur on the patient. Treatment of PJI is complex and requires a combined surgical and medical approach. Patients are often subjected to multiple surgical procedures and prolonged courses of antimicrobial therapy. Therefore, all efforts should be directed toward maximizing the prophylactic measures in the peri-operative and post-operative phases in order to prevent the occurrence of surgical site infections. This article explores primarily the prophylactic measures that target the host and the operative theater environment. Implementation of such preventive measures requires a multi-disciplinary approach and is crucial for a successful outcome of the total joint arthroplasty. PMID- 26855287 TI - Structural Insight into Substrate Selectivity of Erwinia chrysanthemi L asparaginase. AB - l-Asparaginases of bacterial origin are a mainstay of acute lymphoblastic leukemia treatment. The mechanism of action of these enzyme drugs is associated with their capacity to deplete the amino acid l-asparagine from the blood. However, clinical use of bacterial l-asparaginases is complicated by their dual l asparaginase and l-glutaminase activities. The latter, even though representing only ~10% of the overall activity, is partially responsible for the observed toxic side effects. Hence, l-asparaginases devoid of l-glutaminase activity hold potential as safer drugs. Understanding the key determinants of l-asparaginase substrate specificity is a prerequisite step toward the development of enzyme variants with reduced toxicity. Here we present crystal structures of the Erwinia chrysanthemi l-asparaginase in complex with l-aspartic acid and with l-glutamic acid. These structures reveal two enzyme conformations-open and closed corresponding to the inactive and active states, respectively. The binding of ligands induces the positioning of the catalytic Thr15 into its active conformation, which in turn allows for the ordering and closure of the flexible N terminal loop. Notably, l-aspartic acid is more efficient than l-glutamic acid in inducing the active positioning of Thr15. Structural elements explaining the preference of the enzyme for l-asparagine over l-glutamine are discussed with guidance to the future development of more specific l-asparaginases. PMID- 26855289 TI - Biomethane production system: Energetic analysis of various scenarios. AB - The energy consumption models of biomethane production system were established, which are more rigorous and universal than the empirical data reported by previous biomethane system energetic assessment work. The energy efficiencies of different scenarios considering factors such as two digestion modes, two heating modes of digester, with or without heat exchange between slurry and feedstock, and four crude biogas upgrading technologies were evaluated. Results showed the scenario employing thermophilic digestion and high pressure water scrubbing technology, with heat exchange between feedstock and slurry, and heat demand of digester supplied by the energy source outside the system has the highest energy efficiency (46.5%) and lowest energy consumption (13.46 MJth/Nm(3) CH4), while scenario employing mesophilic digestion and pressure swing adsorption technology, without heat exchange and heat demand of digester supplied by combusting the biogas produced inside the system has the lowest energy efficiency (15.8%) and highest energy consumption (34.90 MJth/Nm(3) CH4). PMID- 26855290 TI - Thermodynamic modeling of small scale biomass gasifiers: Development and assessment of the ''Multi-Box'' approach. AB - Modeling can be a powerful tool for designing and optimizing gasification systems. Modeling applications for small scale/fixed bed biomass gasifiers have been interesting due to their increased commercial practices. Fixed bed gasifiers are characterized by a wide range of operational conditions and are multi-zoned processes. The reactants are distributed in different phases and the products from each zone influence the following process steps and thus the composition of the final products. The present study aims to improve the conventional 'Black Box' thermodynamic modeling by means of developing multiple intermediate 'boxes' that calculate two phase (solid-vapor) equilibriums in small scale gasifiers. Therefore the model is named ''Multi-Box''. Experimental data from a small scale gasifier have been used for the validation of the model. The returned results are significantly closer with the actual case study measurements in comparison to single-stage thermodynamic modeling. PMID- 26855291 TI - Reply to "Passive leg raising in CPR: Increasing the effectiveness of each compression". PMID- 26855292 TI - Inflation breaths-A transatlantic divide in guidelines for neonatal resuscitation. PMID- 26855293 TI - Response to: Inflation breaths-A transatlantic divide in guidelines for neonatal resuscitation. PMID- 26855295 TI - Cathodoluminescence study of Mg activation in non-polar and semi-polar faces of undoped/Mg-doped GaN core-shell nanorods. AB - Spectrally and spatially resolved cathodoluminescence (CL) measurements were carried out at 80 K on undoped/Mg-doped GaN core-shell nanorods grown by selective area growth metalorganic vapor phase epitaxy in order to investigate locally the optical activity of the Mg dopants. A study of the luminescence emission distribution over the different regions of the nanorods is presented. We have investigated the CL fingerprints of the Mg incorporation into the non-polar lateral prismatic facets and the semi-polar facets of the pyramidal tips. The amount of Mg incorporation/activation was varied by using several Mg/Ga flow ratios and post-growth annealing treatment. For lower Mg/Ga flow ratios, the annealed nanorods clearly display a donor-acceptor pair band emission peaking at 3.26-3.27 eV and up to 4 LO phonon replicas, which can be considered as a reliable indicator of effective p-type Mg doping in the nanorod shell. For higher Mg/Ga flow ratios, a substantial enhancement of the yellow luminescence emission as well as several emission subbands are observed, which suggests an increase of disorder and the presence of defects as a consequence of the excess Mg doping. PMID- 26855294 TI - Exploratory study of serum ubiquitin carboxyl-terminal esterase L1 and glial fibrillary acidic protein for outcome prognostication after pediatric cardiac arrest. AB - INTRODUCTION: Brain injury is the leading cause of morbidity and death following pediatric cardiac arrest. Serum biomarkers of brain injury may assist in outcome prognostication. The objectives of this study were to evaluate the properties of serum ubiquitin carboxyl-terminal esterase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) to classify outcome in pediatric cardiac arrest. METHODS: Single center prospective study. Serum biomarkers were measured at 2 time points during the initial 72 h in children after cardiac arrest (n=19) and once in healthy children (controls, n=43). We recorded demographics and details of the cardiac arrest and resuscitation. We determined the associations between serum biomarker concentrations and Pediatric Cerebral Performance Category (PCPC) at 6 months (favorable (PCPC 1-3) or unfavorable (PCPC 4-6)). RESULTS: The initial assessment (time point 1) occurred at a median (IQR) of 10.5 (5.5-17.0)h and the second assessment (time point 2) at 59.0 (54.5-65.0)h post-cardiac arrest. Serum UCH-L1 was higher among children following cardiac arrest than among controls at both time points (p<0.05). Serum GFAP in subjects with unfavorable outcome was higher at time point 2 than in controls (p<0.05). Serum UCH-L1 at time point 1 (AUC 0.782) and both UCH-L1 and GFAP at time point 2 had good classification accuracy for outcome (AUC 0.822 and 0.796), p<0.05 for all. CONCLUSION: Preliminary data suggest that serum UCH-L1 and GFAP may be of use to prognosticate outcome after pediatric cardiac arrest at clinically-relevant time points and should be validated prospectively. PMID- 26855296 TI - Disseminated primary esophageal malignant melanoma: a possible venous route of metastasis. PMID- 26855297 TI - Presence of small sessile serrated polyps increases rate of advanced neoplasia upon surveillance compared with isolated low-risk tubular adenomas. AB - BACKGROUND AND AIMS: The U.S. Multi-Society Task Force (USMSTF) stratifies patients with sessile serrated polyps (SSPs) without cytologic dysplasia of <10 mm in size as at low risk for metachronous advanced neoplasia and recommends management similar to low-risk conventional tubular adenomas. Evidence supporting the recommended surveillance interval for these low-risk SSPs is limited. We aimed to assess rates of metachronous advanced neoplasia based on the presence of an initial low-risk SSP compared with isolated low-risk tubular adenomas. METHODS: Colonoscopy data were retrieved for 2260 patients found to have an adenoma or SSP on pathology records between 2005 and 2011 at an academic medical center. The 788 patients who met study design criteria were stratified into 4 groups based on the presence of a high- or low-risk adenoma (HRA or LRA) and of a synchronous SSP on initial colonoscopy. The rates of advanced neoplasia at surveillance colonoscopy were then compared between groups. RESULTS: The rate of advanced neoplasia at surveillance in the LRA inclusive of SSP group (12/66, 18.2%) was greater than in the LRA without any SSP group (29/370, 7.8%; P = .019). The rate of advanced neoplasia at surveillance in patients with isolated low-risk SSP (10/56, 17.9%) remained significantly greater than those with isolated low-risk tubular adenomas (29/370, 7.8%; P = .024). The rate of advanced neoplasia upon surveillance in the LRA inclusive of SSP group (18.2%) was comparable with the rate observed in the index HRA without any SSP group (15.9%) (40/252, P = .709). CONCLUSIONS: The rate of advanced neoplasia upon surveillance in patients with initial low-risk SSPs is higher than in patients with initial isolated low-risk tubular adenomas and more similar to patients with initial high risk tubular adenomas. These findings suggest that the rate of metachronous advanced neoplasia in patients with what are considered by USMSTF as "low-risk" SSPs is higher than in those without SSPs. Therefore, a surveillance interval that accounts for the presence of SSPs even in small lesions without cytologic dysplasia should be considered. PMID- 26855298 TI - Impact of ethylene oxide gas sterilization of duodenoscopes after a carbapenem resistant Enterobacteriaceae outbreak. AB - BACKGROUND AND AIMS: Carbapenem-resistant Enterobacteriaceae (CRE) outbreaks have been implicated at several medical institutions involving gastroenterology laboratories and, specifically, duodenoscopes. Currently, there are no specific guidelines to eradicate or prevent the outbreak of this bacteria. We describe ethylene oxide (ETO) gas sterilizations of duodenoscopes to address this issue. METHODS: A complete investigation of the gastroenterology laboratory and an evaluation by the Centers for Disease Control and Prevention concluded that no lapses were found in the reprocessing of the equipment. With no deficiencies to address, we began a novel cleaning process using surgical ETO gas sterilizers in addition to standard endoscope reprocessing recommendations and guidelines, all while trying to eradicate the CRE contamination and prevent future recurrences. We also instituted a surveillance system for recurrence of CRE contamination via monthly cultures of the duodenoscopes. RESULTS: Between October 2013 and April 2014, 589 ERCPs were performed with 645 ETO gas sterilizations of 6 duodenoscopes. Given the extra 16 hours needed to sterilize the duodenoscopes, our institution incurred costs resulting from purchasing additional equipment and surveillance cultures. Four duodenoscopes sustained damage during this period; however, this could not be directly attributed to the sterilization process. Furthermore, after an 18-month success period we encountered a positive CRE culture after sterilization, albeit of a different strain than originally detected during the outbreak. The duodenoscope underwent additional ETO gas sterilization, with a negative repeated culture; all potentially exposed individuals screened negative for CRE. CONCLUSIONS: Proper use of high-level disinfection alone may not eliminate multidrug-resistant organisms from duodenoscopes. In this single-center study, the addition of ETO sterilization and frequent monitoring with cultures reduced duodenoscope contamination and eliminated clinical infections. As such, ETO gas sterilization may provide benefit in further decontamination of duodenoscopes, but further investigation is necessary. PMID- 26855299 TI - Paramedic Perspectives on Barriers to Prehospital Acute Stroke Recognition. AB - BACKGROUND: Emergency Medical Service (EMS) providers are tasked with rapid evaluation, stabilization, recognition, and transport of acute stroke patients. Although prehospital stroke scales were developed to assist with stroke recognition, unrecognized challenges exist in the prehospital setting that hinder accurate assessment of stroke. The goal of this qualitative study was to systematically understand the challenges and barriers faced by paramedics in recognizing stroke presentations in the field. METHODS: Paramedics from 12 EMS agencies serving a mix of rural, suburban, and urban communities in the State of California participated in five focus group discussions. Group size ranged from 3 8, with a total of 28 participants. Demographics of the participants were collected and focus group recordings were transcribed verbatim. Transcripts were subjected to deductive and inductive coding, which identified recurrent and divergent themes. RESULTS: Strong consensus existed around constraints to prehospital stroke recognition; participants cited the diversity of stroke presentations, linguistic diversity, and exam confounded by alcohol and or drug use as barriers to initial evaluation. Also, lack of educational feedback from hospital staff and physicians and continuing medical education on stroke were reported as major deterrents to enhancing their diagnostic acumen. Across groups, participants reported attempting to foster relationships with hospital personnel to augment their educational needs, but this was easier for rural than urban providers. CONCLUSIONS: While challenges to stroke recognition in the field were slightly different for rural and urban EMS, participants concurred that timely, systematic feedback on individual patients and case-based training would strengthen early stroke recognition skills. PMID- 26855300 TI - Serological Survey for Antibodies to Mosquito-Borne Bunyaviruses Among US National Park Service and US Forest Service Employees. AB - Serum samples from 295 employees of Great Smoky Mountains National Park (GRSM), Rocky Mountain National Park (ROMO), and Grand Teton National Park with adjacent Bridger-Teton National Forest (GRTE-BTNF) were subjected to serological analysis for mosquito-borne bunyaviruses. The sera were analyzed for neutralizing antibodies against six orthobunyaviruses: La Crosse virus (LACV), Jamestown Canyon virus (JCV), snowshoe hare virus (SSHV), California encephalitis virus, and Trivittatus virus (TVTV) belonging to the California serogroup and Cache Valley virus (CVV) belonging to the Bunyamwera serogroup. Sera were also tested for immunoglobulin (Ig) G antibodies against LACV and JCV by enzyme-linked immunosorbent assay (ELISA). The proportion of employees with neutralizing antibodies to any California serogroup bunyavirus was similar in all three sites, with the prevalence ranging from 28% to 36%. The study demonstrated a seroprevalence of 3% to CVV across the three parks. However, proportions of persons with antibodies to specific viruses differed between parks. Participants residing in the eastern regions had a higher seroprevalence to LACV, with 24% (18/75) GRSM employees being seropositive. In contrast, SSHV seroprevalence was limited to employees from the western sites, with 1.7% (1/60) ROMO and 3.8% (6/160) GRTE-BTNF employees being positive. Seroprevalence to JCV was noted in employees from all sites at rates of 6.7% in GRSM, 21.7% in ROMO, and 15.6% in GRTE-BTNF. One employee each from ROMO (1.7%) and GRTE-BTNF (1.9%) were positive for TVTV. This study also has illustrated the greater sensitivity and specificity of plaque reduction neutralization test compared to IgG ELISA in conducting serosurveys for LACV and JCV. PMID- 26855301 TI - Use of inhaled corticosteroids in COPD: improving efficacy. AB - Chronic obstructive pulmonary disease (COPD) is a chronic, inflammatory lung disease characterized by airflow limitation that is not fully reversible. The pathological changes in COPD lead to alveolar destruction (emphysema) and chronic airway inflammation, resulting in airflow obstruction and recurrent exacerbations. Inhaled corticosteroids (ICS) are anti-inflammatory agents that are widely used, especially in combination with long-acting beta-agonists, in patients with COPD. Here, we will summarize the benefits and risks of ICS use for COPD, and discuss approaches to more personalized medicine when selecting COPD patients to commence (or withdraw) ICS use. The conclusion arising is that further validation of clinical and biological markers should be undertaken in COPD, in order to individualize ICS therapy to maximize efficacy for patients. PMID- 26855302 TI - The global tuberculosis situation and the inexorable rise of drug-resistant disease. AB - The highly cost-effective DOTS strategy helped to bring the global tuberculosis (TB) epidemic under control in many parts of the world; however, the emergence and spread of drug-resistant strains pose a major threat to these gains. Molecular epidemiology studies, together with recent genomic evidence, provide proof that some drug-resistant strains are highly transmissible with documented epidemic spread. The potential for epidemic replacement of drug-susceptible with drug-resistant strains provides strong motivation for renewed emphasis on TB drug and vaccine development. It also reflects the need for enhanced infection control measures in health care and congregate settings, especially in TB endemic areas. The exploration of preventive therapy options for close contacts of patients with infectious drug-resistant TB also warrants further exploration, in an attempt to break the transmission cycle. Increased population mobility and large scale cross border migration imply that the inexorable rise of drug-resistant TB is not geographically confined; it is a global concern that poses a very real threat to TB endemic and non-endemic settings. Failure to find new solutions will compromise traditional TB control efforts and derail momentum toward future TB elimination. PMID- 26855303 TI - Exploring structural variants in environmentally sensitive gene families. AB - Environmentally sensitive plant gene families like NBS-LRRs, receptor kinases, defensins and others, are known to be highly variable. However, most existing strategies for discovering and describing structural variation in complex gene families provide incomplete and imperfect results. The move to de novo genome assemblies for multiple accessions or individuals within a species is enabling more comprehensive and accurate insights about gene family variation. Earlier array-based genome hybridization and sequence-based read mapping methods were limited by their reliance on a reference genome and by misplacement of paralogous sequences. Variant discovery based on de novo genome assemblies overcome the problems arising from a reference genome and reduce sequence misplacement. As de novo genome sequencing moves to the use of longer reads, artifacts will be minimized, intact tandem gene clusters will be constructed accurately, and insights into rapid evolution will become feasible. PMID- 26855304 TI - Has the connection between polyploidy and diversification actually been tested? AB - Many major clades of angiosperms have several whole genome duplications (polyploidization events) in their distant past, suggesting that polyploidy drives or at least permits diversification. However, data on recently diverged groups are more equivocal, finding little evidence of elevated diversification following polyploidy. The discrepancy may be attributable at least in part to methodology. Many studies use indirect methods, such as chromosome numbers, genome size, and Ks plots, to test polyploidy, although these approaches can be misleading, and often lack sufficient resolution. A direct test of diversification following polyploidy requires a sequence-based approach that traces the history of nuclear genomes rather than species. These methods identify the point of coalescence of ancestral genomes, but may be misleading about the time and thus the extent of diversification. Limitations of existing methods mean that the connection between polyploidy and diversification has not been rigorously tested and remains unknown. PMID- 26855305 TI - Elderly Patients with Severe Traumatic Brain Injury Could Benefit from Surgical Treatment. AB - OBJECTIVE: In elderly patients with severe traumatic brain injury, the use of aggressive versus conservative management remains controversial. The aim of this study was to assess the outcome of surgical alternatives for treatment of severe traumatic intracranial hematoma in patients >=65 years old and identify factors that may contribute to the outcome. METHODS: This retrospective study included 112 patients with traumatic intracranial hematoma. Logistic regression analysis was used to identify independent predictors of unfavorable outcome. The Glasgow Outcome Scale was used to evaluate the outcome. RESULTS: Surgery was performed in 70 (62.5%) patients >=65 years old. A favorable outcome occurred in 33 (47.1%) surgical patients, and 23 (32.9%) surgical patients died. Patients who underwent surgery were less likely to have an unfavorable outcome (52.9% vs. 95.2%) and less likely to die (32.9% vs. 88.1%) at 6 months postinjury compared with patients treated conservatively. Multivariate logistic regression analysis revealed that lower Glasgow Coma Scale score (<=5) was a significant factor associated with unfavorable outcome (odds ratio [OR] = 18.7, 95% confidence interval [CI] = 5.2-95.5, P < 0.001) and mortality (OR = 10.7, 95% CI = 4.4-28.5, P < 0.001). However, neurosurgical intervention was a significant factor to negatively predict unfavorable outcome (OR = 0.03, 95% CI = 0.01-0.1, P < 0.001) and mortality (OR = 0.04, 95% CI = 0.01-0.1, P < 0.001). CONCLUSIONS: This study showed that Glasgow Coma Scale score (<=5) was a major determinant of outcome in elderly patients with severe traumatic brain injury. However, surgical treatment reduced mortality and improved outcome in the elderly patients in this study. PMID- 26855306 TI - Is Patient Age Associated with Perioperative Outcomes After Surgical Resection of Benign Cranial Nerve Neoplasms? AB - OBJECTIVE: Previous studies have demonstrated that increasing age is associated with decreased rates of operative management and gross total resection in patients with vestibular schwannomas. METHODS: The American College of Surgeons National Surgical Quality Improvement Program data registry was used for this retrospective cohort analysis. Patients enrolled in the registry from 2007 to 2013 with a diagnosis of a benign neoplasm of a cranial nerve were included. The association between age and postoperative morbidity and mortality was evaluated by the use of multivariable logistic regression analyses. RESULTS: Of 565 patients included for analysis, the mean (median) age was 51 (53) years. Three clusters were evaluated: <50, 50-69, and >=70 years. Mortality (0% vs. 1.03% vs. 4.55%, P = 0.012), stroke (0% vs. 0.69% vs. 6.82%, P < 0.001), and ventilator weaning failure (0.43% vs. 2.41% vs. 6.82%, P = 0.014) increased with age. Mean age was significantly greater among patients who died (70.60 vs. 50.87 years, P = 0.002) or had a stroke (68.00 vs. 50.89 years, P = 0.006), cardiac arrest (71.50 vs. 50.89 years, P = 0.038), or coma (74.00 vs. 50.96 years, P = 0.020) and those who failed ventilator weaning (62.55 vs. 50.82, P = 0.006). Age as both a continuous (odds ratio 1.10, 95% confidence interval 1.03-1.18) and categorical variable (age 70+ years odds ratio 78.88, 95% confidence interval 3.41-1825.57) was associated with an increased odds of composite morbidity. CONCLUSIONS: In patients undergoing surgery for benign cranial nerve neoplasms, increasing age is associated with increased mortality, stroke, coma, and ventilator weaning failure. Composite complication rates are significantly greater in patients >=70 years, with a near 80-fold increased risk of complications. PMID- 26855308 TI - Defensive Medicine: A Game in Which Perception Trumps Reality. PMID- 26855307 TI - Prognostic Value of O-(2-[18F]-Fluoroethyl)-L-Tyrosine-Positron Emission Tomography Imaging for Histopathologic Characteristics and Progression-Free Survival in Patients with Low-Grade Glioma. AB - OBJECTIVE: O-(2-[18F]-fluoroethyl)-L-tyrosine positron emission tomography ((18)F FET-PET) imaging is applied for tumor grading, prognostic stratification, and diagnosis of tumor recurrence, especially in high-grade gliomas. Experience with (18)F-FET-PET imaging in low-grade gliomas is limited. Therefore, the objective of the present study was to assess (18)F-FET-PET tracer uptake in low-grade gliomas and to investigate possible correlations with contrast enhancement in magnetic resonance imaging (MRI) and histopathology. METHODS: A total of 65 patients (29 female, 36 male, median age 38 years) with newly diagnosed or recurrent low-grade gliomas for whom preoperative MRI and (18)F-FET-PET imaging were available were included. Tumor entity, tumor location, as well as histopathology (isocitrate dehydrogenase [IDH] 1/2 mutation, Ki67, p53, oligodendroglial differentiation, 1p19q codeletion), and progression-free survival were assessed. (18)F-FET-PET images were acquired and fused to MRI (T2 weighted fluid-attenuated inversion recovery) and tumor volume was measured in areas with a tumor-to-background ratio >1.3, >1.6, and >2.0 and in MRI. RESULTS: PET tracer uptake was observed in 78.5% of all World Health Organization Grade I and II tumors. (18)F-FET uptake showed a high negative predictive value for oligodendroglial components and for 1p19q codeletion. No further significant correlation between histologic features, progression-free survival, or IDH1/2 mutation status and tracer uptake was observed. CONCLUSIONS: We found that 78.5% of low-grade gliomas do show elevated tracer uptake in (18)F-FET-PET imaging. Low grade glioma without tracer uptake exclude oligodendroglial differentiation and 1p19q codeletion. Further differentiation between molecular subtypes is not possible with static (18)F-FET-PET. No correlation of progression-free survival to tracer uptake and IDH1/2-mutation status was observed. PMID- 26855309 TI - Cerebral Sparganosis in Children: Epidemiologic and Radiologic Characteristics and Treatment Outcomes: A Report of 9 Cases. AB - BACKGROUND: Pediatric cerebral sparganosis has been seldom reported. In the current study, we retrospectively reviewed the clinicopathologic records of 9 consecutive pediatric cases of cerebral sparganosis and analyzed their epidemiologic characteristics and clinical outcomes. METHODS: Our cases included 6 boys and 3 girls, all from rural areas, and their median age at diagnosis was 9.4 (range, 5.8-12.9) years. The median duration of symptoms from onset to definite diagnosis was 21 months (range, 1 week to 3.7 years). RESULTS: Enzyme linked immunosorbent assay revealed that serum anti-sparganosis antibody was positive in 9 of 9 patients and cerebrospinal fluid anti-sparganosis antibody was positive in 4 of 6 patients. Eight patients underwent craniotomy the removal of worms. The patients also received oral praziquantel. They were followed up for 2.2 years to 4.4 years. One patient died, and 8 patients survived. Three cases had poor outcomes whereas the outcome of the remaining 5 cases was satisfactory. CONCLUSIONS: Children are more at risk for sparganosis and cerebral sparganosis may be missed because of unclear epidemiologic history and nonspecific manifestations. Cerebrospinal fluid eosinophil counts and enzyme-linked immunosorbent assay for anti-sparganosis antibody and computed tomography/magnetic resonance imaging scans may be relied on for an early and accurate diagnosis before surgery. PMID- 26855310 TI - Social Media Metrics and Bibliometric Profiles of Neurosurgical Departments and Journals: Is There a Relationship? AB - BACKGROUND: Social media plays an increasingly important role in dissemination of knowledge and raising awareness of selected topics among the general public and the academic community. OBJECTIVE: To investigate the relationship between social media metrics and academic indices of neurosurgical programs and journals. METHODS: A 2-step online search was performed to identify official social media accounts of neurosurgical departments that were accredited by the Accreditation Council for Graduate Medical Education and the Royal College of Physicians and Surgeons of Canada. Dedicated neurosurgery and spine journals' social media accounts also were identified through an online search on SCImago Journal and Country Rank portal. Nonparametric tests were performed with bootstrapping to compare groups and to look for correlations between social media and academic metrics. RESULTS: We identified 36 social media accounts officially affiliated with academic neurosurgical institutions. These accounts represented 22 of 119 neurosurgical programs in North America (18.4%). The presence of a social media account for neurosurgical departments was associated with statistically significant higher values of academic impact metrics (P < 0.05). Specific social media metrics for neurosurgical department accounts, however, did not correlate with any values of academic indices. For journals, there were 11 journals present on social media and had greater academic metrics compared with journals without social media presence (P < 0.05). CONCLUSIONS: Social media presence is associated with stronger academic bibliometrics profiles for both neurosurgical departments and journals. The impact of social media metrics on indices of scientific impact in neurosurgery is not known. PMID- 26855311 TI - Primary Intraventricular Leiomyoma in an Immunocompetent Patient: First Case Report and Review of the Literature. AB - BACKGROUND: Primary intracranial leiomyoma is an extremely rare occurrence of a low-grade mesenchymal tumor characterized by a proliferation of smooth muscle cells. When present, these lesions predominantly occur in immunocompromised patients in the setting of infection or transplant and have not been known to involve the ventricular system of the brain. In this report, we describe a case of primary leiomyoma of the lateral ventricle in an immunocompetent patient. CASE DESCRIPTION: A 30-year-old man with no medical history presented with progressive diplopia and occipital headaches. Magnetic resonance imaging of the brain revealed a homogenously enhancing mass of the left lateral ventricle with associated cerebral edema. The patient underwent interhemispheric transcallosal craniotomy for resection for symptom alleviation and surgical diagnosis. Histopathology and immunohistochemistry was subsequently consistent with that of leiomyoma. Genetic probing for Epstein-Barr virus was negative. Computed tomography of the chest and abdomen failed to uncover a primary tumor. The patient did well postoperatively and was discharged 3 days after resection. At a two-and-a-half year follow-up, there continued to be no radiologic or clinical evidence of recurrence. CONCLUSIONS: To date and to our knowledge, there are fewer than 25 reported cases of primary intracranial leiomyoma, with only 13 occurring in immunocompetent individuals. We believe this is the first report of this tumor type occurring within the ventricular system of the brain. As such, leiomyoma should be considered as a rare etiology in the differential diagnosis of intraventricular lesions. PMID- 26855312 TI - The Important Liaison Between Onuf Nucleus-Pudendal Nerve Ganglia Complex Degeneration and Urinary Retention in Spinal Subarachnoid Hemorrhage: An Experimental Study. AB - OBJECTIVE: The Adamkiewicz artery (AKA) supplies pudendal nerve roots and conus medullaris. The aim of this study was to elucidate if there is any relationship between neurodegenerative changes of the Onuf nucleus (ON)-pudendal nerve ganglia complex secondary to vasospasm of the AKA after spinal subarachnoid hemorrhage (SAH). METHODS: This study was conducted on 22 rabbits, which were randomly divided into 3 groups: control (n = 5), sham (n = 5), and spinal SAH (n = 12). Experimental spinal SAH was induced at the L2 level. After 2 weeks, the ON pudendal nerve ganglia complex and AKA were examined histopathologically. Bladder volume values were estimated, and results were analyzed statistically. RESULTS: Two animals died within the first week of experiment. Histopathologically, severe vasospasm of the AKA and neuronal degeneration and neuronal apoptosis were observed in the ON-pudendal nerve ganglia complex in 5 animals of the SAH group. The mean volume of the imaginary AKA, mean bladder volumes, and degenerated neuron densities of ON and pudendal nerve ganglia were estimated. We found that vasospasm of the AKA led to numerous neuron degenerations in ON and pudendal ganglia and consequently urinary retention (P < 0.005). CONCLUSIONS: ON-pudendal nerve ganglia complex degeneration secondary to vasospasm of the AKA may be a cause of urinary retention after spinal SAH. PMID- 26855313 TI - Subcompartmentalized Nanoreactors as Artificial Organelle with Intracellular Activity. AB - Cell mimicry is an approach which aims at substituting missing or lost activity. In this context, the goal of artificial organelles is to provide intracellularly active nanoreactors to affect the cellular performance. So far, only a handful of reports discuss concepts addressing this challenge based on single-component reactors. Here, the assembly of nanoreactors equipped with glucose oxidase (GOx) loaded liposomal subunits coated with a poly(dopamine) polymer layer and RGD targeting units is reported. When comparing different surface modifications, the uptake of the nanoreactors by endothelial cells and macrophages with applied shear stress is confirmed without inherent cytotoxicity. Furthermore, the encapsulation and preserved activity of GOx within the nanoreactors is shown. The intracellular activity is demonstrated by exposing macrophages with internalized nanoreactors to glucose and assessment of the cell viability after 6 and 24 h. The macrophage viability is found to be reduced due to the intracellularly produced hydrogen peroxide by GOx. This report on the first intracellular active subcompartmentalized nanoreactors is a considerable step in therapeutic cell mimicry. PMID- 26855314 TI - Influence of Liquid Lubrication on the Screw-Joint Stability of Y-TZP Implant Abutment Systems. AB - PURPOSE: To evaluate the effectiveness of abutment screws coated with liquid Vaseline on the screw-joint stability of yttria-stabilized tetragonal zirconia (Y TZP) abutment systems. MATERIALS AND METHODS: Forty Y-TZP prefabricated abutments, 20 Neodent and 20 Bionnovation, were tightened to 20 Ncm on their respective external hexagon implants, and divided into four groups (n = 10) according to the screws: coated with Vaseline or uncoated. The removal torque (RT) value of the abutment screw was measured before and after loading. A cyclic loading (0.5 * 106 cycles; 15 Hz) between 11 and 211 N was applied. Means were compared using a repeated-measures ANOVA (alpha = 0.05). RESULTS: There was no significant difference between coated and uncoated screws (p = 0.822). Significant differences were found between the abutment systems (p < 0.001). There was a significant effect of cyclic loading (p < 0.001). CONCLUSIONS: Coated and uncoated screws presented similar effectiveness in maintaining preload. CLINICAL RELEVANCE: The liquid lubricant used in this study does not influence the stability of Y-TZP single-implant restorations. PMID- 26855315 TI - Efficient enzymatic production of hydroxy fatty acids by linoleic acid Delta9 hydratase from Lactobacillus plantarum AKU 1009a. AB - AIMS: This study aims to produce hydroxy fatty acids efficiently. METHODS AND RESULTS: Escherichia coli overexpressing linoleic acid Delta9 hydratase from Lactobacillus plantarum AKU 1009a was employed to produce hydroxy fatty acids with industrial potential. We found that 280 g l(-1) of linoleic acid (1 mol l( 1)) was converted into (S)-10-hydoxy-cis-12-octadecenoic acid (HYA) with a high conversion rate of 98% (mol/mol) and more than 99.9% enantiomeric excess (e.e.) by recombinant E. coli cells in the presence of FAD and NADH. In the same way, many kinds of C18 unsaturated fatty acids with Delta9 carbon double bond (280 g l(-1)) were converted into corresponding 10-hydroxy fatty acids with the conversion rates over 95% (mol/mol). We also produced HYA at a high rate of accumulation (289 g l(-1) ) with a high yield (97 mol%) in a reaction mixture that contained glucose instead of NADH. CONCLUSIONS: We developed a process for producing several types of hydroxy fatty acids with high accumulation rates and high yields. SIGNIFICANCE AND IMPACT OF THE STUDY: Hydroxy fatty acids are important materials for the chemical, food, cosmetic and pharmaceutical industries, and thus they have recently attracted much interest in a variety of research fields. However, the mass production of hydroxy fatty acids has been limited. This method of hydroxy fatty acids production will facilitate the widespread application of hydroxy fatty acids in various industries. PMID- 26855316 TI - C5a and pain development: An old molecule, a new target. AB - Pain is a distressing sensation, resulting from real or potential tissue damage. It is crucial to protect our body, but it can be so intense that it requires treatment. Furthermore, in some circumstances, pain can become persistent/chronic, such as that triggered by inflammatory disease or neuropathy. Treatments for pain are still a clinical challenge. An advance in the knowledge of the neurobiological mechanisms involved in the genesis of acute and chronic pain might be the fundamental approach for developing novel classes of analgesic drugs. In this context, there is emerging evidence indicating that C5a, a component of the complement system, and its cell membrane receptor, C5aR, play a critical role in the genesis of acute and chronic pain states. Thus, this review will describe the mechanisms by which C5a/C5aR signaling participates in the cascade of events involved in the pathophysiology of acute (postoperative), inflammatory and neuropathic pain states. Furthermore, it will also highlight the current possibilities for the development of a novel class of analgesic drugs that target C5a/C5aR signaling. PMID- 26855317 TI - Exosomes as a potential novel therapeutic tools against neurodegenerative diseases. AB - Exosomes are extracellular vesicles that can transfer biological information over long distances affecting normal and pathological processes throughout organism. It is known that very often composition and therapeutic properties of exosomes depends on cell type and its physiological state. Thus, depending on tissue of origin and physiological context exosomes may act as promoters, or suppressors of pathological processes in CNS. From the therapeutic perspective, the most promising cellular sources of exosomes are mesenchymal stem cells, dendritic cells and inducible pluripotent stem cells. In this review, we will summarize the current state of knowledge on the molecular mechanisms underlying neuroprotective actions of exosomes derived from these cells. New therapies for the neurodegenerative disorders are often halted by the inability of drugs to cross blood-brain barrier. In this respect exosomes have a critical advantage, because they can cross blood-brain barrier. Despite the great importance, surprisingly little is known about mechanistic details of this process. Therefore we will discuss some recent findings that may explain mechanisms of exosomal entry into the brain. PMID- 26855318 TI - Thyroid hormones and their membrane receptors as therapeutic targets for T cell lymphomas. AB - Thyroid hormones (THs) are important regulators of metabolism, differentiation and cell proliferation. They can modify the physiology of human and murine T cell lymphomas (TCL). These effects involve genomic mechanisms, mediated by specific nuclear receptors (TR), as well as nongenomic mechanisms, that lead to the activation of different signaling pathways through the activation of a membrane receptor, the integrin alphavbeta3. Therefore, THs are able to induce the survival and growth of TCL. Specifically, the signaling induced by THs through the integrin alphavbeta3 activates proliferative and angiogenic programs, mediated by the regulation of the vascular endothelial growth factor (VEGF). The genomic or pharmacologic inhibition of integrin alphavbeta3 reduces the production of VEGF and induces cell death both in vitro and in xenograft models of human TCL. Here we review the mechanisms involved in the modulation of the physiology of TCL induced by THs, the analysis of the interaction between genomic and nongenomic actions of THs and their contribution to T cell lymphomagenesis. These actions of THs suggest a novel mechanism for the endocrine modulation of the physiopathology of TCL and they provide a potential molecular target for its treatment. PMID- 26855319 TI - Glyco-nano-oncology: Novel therapeutic opportunities by combining small and sweet. AB - Recent efforts toward defining the molecular features of the tumor microenvironment have revealed dramatic changes in the expression of glycan related genes including glycosyltransferases and glycosidases. These changes affect glycosylation of proteins and lipids not only in cancer cells themselves, but also in cancer associated-stromal, endothelial and immune cells. These glycan alterations including increased frequency of beta1,6-branched N-glycans and bisecting N-glycans, overexpression of tumor-associated mucins, preferred expression of T, Tn and sialyl-Tn antigen and altered surface sialylation, may contribute to tumor progression by masking or unmasking specific ligands for endogenous lectins, including members of the C-type lectin, siglec and galectin families. Differential expression of glycans or glycan-binding proteins could be capitalized for the identification of novel biomarkers and might provide novel opportunities for therapeutic intervention. This review focuses on the biological relevance of lectin-glycan interactions in the tumor microenvironment (mainly illustrated by the immunosuppressive and pro-angiogenic activities of galectin-1) and the design of functionalized nanoparticles for pharmacological delivery of multimeric glycans, lectins or selective inhibitors of lectin-glycan interactions with antitumor activity. PMID- 26855320 TI - Improvement of oral contraceptive-induced glucose dysregulation and dyslipidemia by valproic acid is independent of circulating corticosterone. AB - CONTEXT: Cardiometabolic disorders are rapidly becoming major public health challenges. Valproic acid (VPA) is a widely prescribed anticonvulsant drug. OBJECTIVE: We hypothesized that treatment with VPA would improve the regulation of glucose and atherogenic dyslipidemia through reduction in circulating corticosterone. METHODS: Female Wistar rats recieved (p.o.) combined oral contraceptive (COC) containing 1.0 ug ethinylestradiol plus 5.0 ug levonorgestrel and valproic acid (VPA; 20 mg) for 8 weeks. RESULTS: Treatment with COC led to elevated fasting blood glucose, insulin, corticosterone, triglycerides (TG), TG/HDL-cholesterol ratio, insulin resistance (IR) and impaired glucose tolerance. VPA significantly attenuated the alterations induced by COC treatment, but did not affect the corticosterone level. However, VPA treatment led to significant increases in plasma insulin, corticosterone, atherogenic lipids and impaired glucose tolerance in rats not treated with COC. CONCLUSION: The findings in this study suggest that VPA mitigates against the development of COC-induced insulin resistance and dyslipidemia independent of elevated circulating corticosterone. PMID- 26855321 TI - TOR (target of rapamycin) is a key regulator of triacylglycerol accumulation in microalgae. AB - Most microalgae abundantly accumulate lipid droplets (LDs) containing triacylglycerols (TAGs) under several stress conditions, but the underlying molecular mechanism of this accumulation remains unclear. In a recent study, we found that inhibition of TOR (target of rapamycin), a highly conserved protein kinase of eukaryotes, by rapamycin resulted in TAG accumulation in microalgae, indicating that TOR negatively regulates TAG accumulation. Here, we show that formation of intracellular LDs and TAG accumulation were also induced in the unicellular green alga Chlamydomonas reinhardtii after exposure to Torin1 or AZD8055, which are novel TOR inhibitors that inhibit TOR activity in a manner different from rapamycin. These results supported quite well our previous conclusion that TOR is a central regulator of TAG accumulation in microalgae. PMID- 26855322 TI - Association of FEF25-75% Impairment with Bronchial Hyperresponsiveness and Airway Inflammation in Subjects with Asthma-Like Symptoms. AB - BACKGROUND: Forced expiratory flow at 25 and 75% of the pulmonary volume (FEF25 75%) might be considered as a marker of early airway obstruction. FEF25-75% impairment might suggest earlier asthma recognition in symptomatic subjects even in the absence of other abnormal spirometry values. OBJECTIVES: The study was designed in order to verify whether FEF25-75% impairment in a cohort of subjects with asthma-like symptoms could be associated with the risk of bronchial hyperresponsiveness (BHR) and with airway inflammation expressed as fractional exhaled nitric oxide (FeNO) and eosinophil counts in induced sputum. METHODS: Four hundred adults with a history of asthma-like symptoms (10.5% allergic) underwent spirometry, determination of BHR to methacholine (PD20FEV1), FeNO analysis and sputum induction. FEF25-75% <65% of predicted or <-1.64 z-score was considered abnormal. RESULTS: All subjects had normal FVC, FEV1 and FEV1/FVC, while FEF25-75% was abnormal in 27.5% of them. FEF25-75% (z-score) was associated with PD20FEV1 (p < 0.001), FeNO (p < 0.001) and sputum eosinophils (p < 0.001). Patients with abnormal FEF25-75% showed higher levels of FeNO and eosinophils in induced sputum than did patients with normal FEF25-75% (p < 0.01 and p < 0.01, respectively). Subjects with abnormal FEF25-75% had an increased probability of being BHR positive (OR = 13.38; 95% CI: 6.7-26.7; p < 0.001). CONCLUSIONS: Our data show that abnormal FEF25-75% might be considered an early marker of airflow limitation associated with eosinophilic inflammation and BHR in subjects with asthma-like symptoms, indicating a role for FEF25-75% as a predictive marker of newly diagnosed asthma. PMID- 26855323 TI - A Water-Stable Cationic Metal-Organic Framework as a Dual Adsorbent of Oxoanion Pollutants. AB - A three-dimensional water-stable cationic metal-organic framework (MOF) pillared by a neutral ligand and with Ni(II) metal nodes has been synthesized employing a rational design approach. Owing to the ordered arrangement of the uncoordinated tetrahedral sulfate (SO4 (2-) ) ions in the channels, the compound has been employed for aqueous-phase ion-exchange applications. The compound exhibits rapid and colorimetric aqueous-phase capture of environmentally toxic oxoanions (with similar geometries) in a selective manner. This system is the first example of a MOF-based system which absorbs both dichromate (Cr2 O7 (2-) ) and permanganate (MnO4 (-) ) ions, with the latter acting as a model for the radioactive contaminant pertechnetate (TcO4 (-) ). PMID- 26855324 TI - Effect of proton pump inhibitors and antibiotics on the gut microbiome of hospitalised older persons. PMID- 26855325 TI - Local field potentials in the ventral tegmental area during cocaine-induced locomotor activation: Measurements in freely moving rats. AB - The ventral tegmental area (VTA) has been established as a critical nucleus for processing behavioral changes that occur during psychostimulant use. Although it is known that cocaine induced locomotor activity is initiated in the VTA, not much is known about the electrical activity in real time. The use of our custom designed wireless module for recording local field potential (LFP) activity provides an opportunity to confirm and identify changes in neuronal activity within the VTA of freely moving rats. The purpose of this study was to investigate the changes in VTA LFP activity in real time that underlie cocaine induced changes in locomotor behavior. Recording electrodes were implanted in the VTA of rats. Locomotor behavior and LFP activity were simultaneously recorded at baseline, and after saline and cocaine injections. Results indicate that cocaine treatment caused increases in both locomotor behavior and LFP activity in the VTA. Specifically, LFP activity was highest during the first 30 min following the cocaine injection and was most robust in Delta and Theta frequency bands; indicating the role of low frequency VTA activity in the initiation of acute stimulant-induced locomotor behavior. Our results suggest that LFP recording in freely moving animals can be used in the future to provide valuable information pertaining to drug induced changes in neural activity. PMID- 26855326 TI - Systemic administration of vitamins C and E attenuates nociception induced by chronic constriction injury of the sciatic nerve in rats. AB - Antioxidants have been tested to treat neuropathic pain, and alpha-Tocopherol (vitamin E--vit. E) and ascorbic acid (vitamin C--vit. C) are potent antioxidants. We assessed the effect of intraperitoneal administration of vit. C (30 mg/kg/day) and vit. E (15 mg/kg/day), given alone or in combination, on the mechanical and thermal thresholds and the sciatic functional index (SFI) in rats with chronic constriction injury (CCI) of the sciatic nerve. We also determined the lipid hydroperoxides and total antioxidant capacity (TAC) in the injured sciatic nerve. Further, we assessed the effects of oral administration of vit. C+vit. E (vit. C+E) and of a combination of vit. C+E and gabapentin (100mg/kg/day, i.p.) on the mechanical and thermal thresholds of CCI rats. The vitamins, whether administered orally or i.p., attenuated the reductions in the mechanical and thermal thresholds induced by CCI. The antinociceptive effect was greater with a combination of vit. C+E than with each vitamin given alone. The SFI was also improved in vitamin-treated CCI rats. Co-administration of vit. C+E and gabapentin induced a greater antinociceptive effect than gabapentin alone. No significant change occurred in TAC and lipid hydroperoxide levels, but TAC increased (45%) while lipid hydroperoxides decreased (38%) in the sciatic nerve from vit. C+E-treated CCI rats. Thus, treatment with a combination of vit. C+E was more effective to treat CCI-induced neuropathic pain than vitamins alone, and the antinociceptive effect was greater with co-administration of vit. C+E and gabapentin than with gabapentin alone. PMID- 26855327 TI - The behavioural profile of gamma-hydroxybutyrate, gamma-butyrolactone and 1,4 butanediol in humans. AB - Gamma-hydroxybutyrate (GHB) is a putative neurotransmitter, a drug of abuse, and a medical treatment for narcolepsy and other neuropsychiatric disorders. Its precursors gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD) are endogenously converted to GHB and thereby exert their psychobehavioural effects. In humans, GHB has a wide spectrum of properties ranging from stimulation and euphoria in lower doses, to sedation, deep sleep, and coma after ingestion of high doses. However, behavioural studies in healthy volunteers remain scarce and are usually limited to psychomotor performance testing. Most available data arise from either qualitative studies with illicit users or clinical trials examining therapeutic properties of GHB (then usually termed sodium oxybate). Here, we present an overview of the behavioural effects of GHB, GBL, and 1,4-BD in these three populations. GHB and its precursors strongly influence behaviours related to core human autonomic functions such as control of food intake, sexual behaviour, and sleep-wake regulation. These effects are instrumentalised by illicit users and clinically utilised in neuropsychiatric disorders such as narcolepsy, fibromyalgia, and binge-eating syndrome. Considering the industry withdrawal from psychopharmacology development, repurposing of drugs according to their behavioural and clinical profiles has gained increasing relevance. As such, GHB seems to be an attractive candidate as an experimental therapeutic in depression. PMID- 26855328 TI - Retracted: Postoperative pain after irrigation with Vibringe versus a conventional needle: a randomized controlled trial. AB - The following article from International Endodontic Journal, 'Postoperative pain after irrigation with Vibringe versus a conventional needle: a randomized controlled trial' by D. Bilgili, S. Yilmaz, A. Dumani & O. Yoldas, published online on 29 February 2016 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the Journal Editor in Chief, Prof. Paul Dummer, and John Wiley & Sons Ltd. The retraction has been agreed because the corresponding author did not contact the first author who carried out the work before alterations to the article were made prior to submission. This damages the integrity of the work and there are additional concerns over the number of patients and the accuracy of the results and conclusions. PMID- 26855329 TI - Mcl-1 regulates effector and memory CD8 T-cell differentiation during acute viral infection. AB - Mcl-1, an anti-apoptotic member of Bcl-2 family maintains cell viability during clonal expansion of CD8 T cells, but the cell intrinsic role of Mcl-1 in contraction of effectors or the number of memory CD8 T cells is unknown. Mcl-1 levels decline during the contraction phase but rebound to high levels in memory CD8 T cells. Therefore, by overexpressing Mcl-1 in CD8 T cells we asked whether limiting levels of Mcl-1 promote contraction of effectors and constrain CD8 T cell memory. Mcl-1 overexpression failed to affect CD8 T-cell expansion, contraction or the magnitude of CD8 T-cell memory. Strikingly, high Mcl-1 levels enhanced mTOR phosphorylation and augmented the differentiation of terminal effector cells and effector memory CD8 T cells to the detriment of poly-cytokine producing central memory CD8 T cells. Taken together, these findings provided unexpected insights into the role of Mcl-1 in the differentiation of effector and memory CD8 T cells. PMID- 26855331 TI - Swine alveolar macrophage cell model allows optimal replication of influenza A viruses regardless of their origin. AB - The importance of pigs in interspecies transmission of influenza A viruses has been repeatedly demonstrated over the last century. Eleven influenza A viruses from avian, human and swine hosts were evaluated for replication phenotypes at three physiologically relevant temperatures (41 degrees C, 37 degrees C, 33 degrees C) in an immortalized swine pulmonary alveolar macrophage cell line (IPAM 3D4/31) to determine whether this system would allow for their efficient replication. All isolates replicated well in IPAMs at 37 degrees C while clear distinctions were observed at 41 degrees C and 33 degrees C, correlating to species of origin of the PB2, reflected in distinct amino acid residue profiles rather than in one particular PB2 residue. A strong TNF-alpha response was induced by some mammalian but not avian IAVs, while other selected cytokines remained below detection levels. Porcine IPAMs represent a natural host cell model for influenza virus replication where the only condition requiring modification for optimal IAV replication, regardless of virus origin. PMID- 26855330 TI - Next generation sequencing of DNA-launched Chikungunya vaccine virus. AB - Chikungunya virus (CHIKV) represents a pandemic threat with no approved vaccine available. Recently, we described a novel vaccination strategy based on iDNA(r) infectious clone designed to launch a live-attenuated CHIKV vaccine from plasmid DNA in vitro or in vivo. As a proof of concept, we prepared iDNA plasmid pCHIKV-7 encoding the full-length cDNA of the 181/25 vaccine. The DNA-launched CHIKV-7 virus was prepared and compared to the 181/25 virus. Illumina HiSeq2000 sequencing revealed that with the exception of the 3' untranslated region, CHIKV 7 viral RNA consistently showed a lower frequency of single-nucleotide polymorphisms than the 181/25 RNA including at the E2-12 and E2-82 residues previously identified as attenuating mutations. In the CHIKV-7, frequencies of reversions at E2-12 and E2-82 were 0.064% and 0.086%, while in the 181/25, frequencies were 0.179% and 0.133%, respectively. We conclude that the DNA launched virus has a reduced probability of reversion mutations, thereby enhancing vaccine safety. PMID- 26855332 TI - PI3K-Akt signaling pathway upregulates hepatitis C virus RNA translation through the activation of SREBPs. AB - Hepatitis C virus (HCV) activates PI3K-Akt signaling to enhance entry and replication. Here, we found that this pathway also increased HCV translation. Knocking down the three Akt isoforms significantly decreased, whereas ectopic expression increased HCV translation. HCV translation upregulation by Akt required their kinase activities because Akt kinase-dead mutants downregulated HCV translation; and was dependent on PI3K activity since it was sensitive to PI3K inhibitor wortmannin. The viral 3'UTR was not involved in translation upregulation by Akt. HCV NS5A increased Akt phosphorylation/activity and HCV translation in the absence of the viral 3'UTR. Sterol regulatory element-binding proteins (SREBPs) were the downstream effectors of the PI3K-Akt pathway in regulating HCV translation because Akt1 and Akt2 activated both SREBP-1 and SREBP 2, whereas Akt3 upregulated SREBP-1. Knocking down SREBPs significantly decreased, while ectopic expression of SREBPs increased HCV translation. Taken together, we showed that the PI3K-Akt signaling pathway positively regulates HCV translation through SREBPs. PMID- 26855334 TI - The lung in rheumatoid arthritis, cause or consequence? Erratum. AB - The name of the one of the first authors is spelt incorrectly in the article, 'The lung in rheumatoid arthritis, cause or consequence? The correct spelling is Aikaterini Chatzidionysiou. PMID- 26855333 TI - Selection and use of immunosuppressive therapies after liver transplantation: current German practice. AB - In recent years, immunosuppression (IS) after liver transplantation (LT) has become increasingly diversified as the choice of agents has expanded and clinicians seek to optimize the balance of immunosuppressive potency with the risk of adverse events in individual patients. Calcineurin inhibitors (CNIs) are the primary agents used for patients undergoing liver transplantation. Other therapeutic agents like interleukin-2 receptor antagonists are not universally administered, but can be considered for the delay or reduction in CNI exposure. An early addition of mycophenolate mofetil (MMF) or the mTOR inhibitor everolimus also allows for the reduction in the CNI dose. To reduce the risk of malignancy, in particular of skin tumors, as well as to prevent the deterioration of renal function, everolimus-based therapy may be advantageous. Apart from patients with autoimmune hepatitis, steroids are withdrawn within 3-6 months after transplantation. Overall, immunosuppression can only be standardized in a limited proportion of patients due to specific clinical requirements and risk factors. Future studies should attempt to refine accurate individualization of the immunosuppressive regimen in specific difficult-to-treat patient subpopulations. PMID- 26855335 TI - Stable mixed chimerism and tolerance to human organ transplants. AB - Tolerance to combined kidney and hematopoietic cell transplant has been achieved in humans after establishment of mixed chimerism allowing for the withdrawal of immunosuppressive drugs. The seminal contributions of Ray Owen provided the scientific basis for the human protocol. PMID- 26855337 TI - A CHALLENGING CASE OF SEVERE INFANTILE CHOLESTASIS IN ALPHA-1 ANTITRYPSIN DEFICIENCY. AB - Jaundice in the newborn period can be physiologic and is often due to benign causes. Jaundice due to conjugated hyperbilirubinemia extending beyond the second week of life may be an early sign of several cholestatic or metabolic liver diseases, and it requires logical and timely analysis so that specific treatments can be initiated. A1AT deficiency is the most common genetic cause of pediatric liver disease and transplantation, and it must be considered when evaluating cholestatic infants. Here, we present an unusual case of A1AT deficiency with severe infantile cholestasis and rapid decompensation in the first 4 months of life, where in-depth but timely diagnosis was crucial for the appropriate intervention to take place. PMID- 26855339 TI - Jinx or Not?: There Is Nothing Like a "Black Cloud" Syndrome. AB - OBJECTIVE: The aim of this study was to ascertain the validity of the widespread belief in the existence of jinxed physicians during night duty in emergency department (ED). METHODS: We conducted a retrospective study involving 13 pediatricians with more than 12 spells of night duty (8 PM to 8.30 AM) in the ED at the "La Timone" Medical School Hospital in Marseilles, France, during the inclusion period (from November 1, 2010, to October 31, 2011) and 8 night nurses in the same ED. The 13 pediatricians rated themselves as jinxed and were rated as such by their peers and the night nurses. The number of ED visits (total, medical, and after midnight) and the number of hospitalizations were compared according to the jinx rating of the 13 pediatricians. The secondary outcome was a comparison of the self-assessed jinxed pediatrician group with the other group. RESULTS: Four pediatricians rated themselves as jinxes. Despite a nonperfect match, self-assessed jinxed pediatricians were also more often rated as being jinxed by their peers or the nurses. There was no difference (for the 13 pediatricians) regarding total ED visits (31.6 [14-57], P = 0.98), ED visits after midnight (10.37 [1-26], P = 0.876), and the number of hospitalizations (4.5 [0-12], P = 0.179). The number of ED visits (total, medical, after midnight) did not differ from the jinxed physicians (all P >0.20) to the other pediatricians, but the mean number of hospitalizations was higher when the pediatrician was rated as a jinx (4.9 vs 4.3, P = 0.034). CONCLUSIONS: We found no evidence of a jinx effect on workload in a pediatric ED. PMID- 26855336 TI - Complementary subicular pathways to the anterior thalamic nuclei and mammillary bodies in the rat and macaque monkey brain. AB - The origins of the hippocampal (subicular) projections to the anterior thalamic nuclei and mammillary bodies were compared in rats and macaque monkeys using retrograde tracers. These projections form core components of the Papez circuit, which is vital for normal memory. The study revealed a complex pattern of subicular efferents, consistent with the presence of different, parallel information streams, whose segregation appears more marked in the rat brain. In both species, the cells projecting to the mammillary bodies and anterior thalamic nuclei showed laminar separation but also differed along other hippocampal axes. In the rat, these diencephalic inputs showed complementary topographies in the proximal-distal (columnar) plane, consistent with differential involvement in object-based (proximal subiculum) and context-based (distal subiculum) information. The medial mammillary inputs, which arose along the anterior posterior extent of the rat subiculum, favoured the central subiculum (septal hippocampus) and the more proximal subiculum (temporal hippocampus). In contrast, anterior thalamic inputs were largely confined to the dorsal (i.e. septal and intermediate) subiculum, where projections to the anteromedial nucleus favoured the proximal subiculum while those to the anteroventral nucleus predominantly arose in the distal subiculum. In the macaque, the corresponding diencephalic inputs were again distinguished by anterior-posterior topographies, as subicular inputs to the medial mammillary bodies predominantly arose from the posterior hippocampus while subicular inputs to the anteromedial thalamic nucleus predominantly arose from the anterior hippocampus. Unlike the rat, there was no clear evidence of proximal-distal separation as all of these medial diencephalic projections preferentially arose from the more distal subiculum. PMID- 26855340 TI - Pediatric Spontaneous Pneumomediastinum: Narrative Literature Review. AB - INTRODUCTION: Described since 1939 in the adult population, spontaneous pneumomediastinum is less known in children. Because of its symptoms and a generally benign evolution, it is probably an underestimated diagnosis. However, it has to be considered in the differential diagnosis of acute thoracic pain. METHODS: The incidence being low, we conducted a narrative literature review to identify the circumstances leading to a spontaneous pneumomediastinum, the most relevant signs and symptoms, investigations, as well as treatment recommendations. RESULTS: Of 216 patients, 66.2% are boys, and mean ages range from 6.9 to 14 years. The most frequent comorbidity in children is asthma (22.2%), and the most common trigger factors are bronchospasm (49%), cough (45.6%), various respiratory tract infections, vomiting (10.3%), and foreign body aspiration (8.3%). It remains idiopathic in 33.3%. Relevant signs are chest pain (54.6%), neck pain and/or sore throat (53.3%), and dyspnea (41.2%). The most relevant sign is palpation of subcutaneous emphysema (66.4%). The classically described Hamman crunch is only present in 11.6%. Chest x-ray provides the right diagnosis in 99.5% of the patients. Pneumothorax is associated in 11.6%. Most patients are hospitalized (88.3%); treatment is based on oxygen therapy, painkillers, and rest. In some series, there can be up to 25.8% of patients requiring intensive care and 5.5% requiring drainage of associated pneumothorax. Survival rate is 92.5%, and long-term follow-up shows normal x-rays after 4 days and no recurrence. CONCLUSIONS: Spontaneous pneumomediastinum is uncommon in children but must be considered in pediatric patients with acute chest and/or neck pain. History taking, physical examination, and standard chest x-ray are most often diagnostic, and there is rarely a need for other investigation.Hospitalization is not always indispensable; ambulatory management can be considered. Outcome is good, and follow-up can be clinical, therefore avoiding further x-rays. PMID- 26855338 TI - Cardamonin inhibited cell viability and tumorigenesis partially through blockade of testes-specific protease 50-mediated nuclear factor-kappaB signaling pathway activation. AB - Previous studies have shown that testes-specific protease 50 (TSP50), a pro oncogene overexpressed in many types of tumors, could promote cell proliferation, invasion, tumorigenesis, and tumor metastasis, suggesting that it is a potential cancer therapeutic target in drug discovery. Here, a luciferase assay system driven by the TSP50 gene promoter was used to screen the inhibitor of expression of TSP50. The study found that cardamonin, a flavone compound, could efficiently inhibit the expression of TSP50 in both mRNA and protein levels. Further results revealed that cardamonin also efficiently inhibited the viability of TSP50 high expressing cancer cells by inducing G2/M-phase arrest and mitochondrial-dependent apoptosis. Surprisingly, knocking down the expression of TSP50 gene had the same effects as treatment with cardamonin. Moreover, it has been found that cardamonin had an inhibitory potency on TSP50 high-expressing tumor growth in vivo. In contrast, overexpression of TSP50 greatly decreased the cell sensitivity to the inhibitory effect of cardamonin and reversed the decreased tumor-inhibitory effect of cardamonin. Additionally, both TSP50 interference and treatment with cardamonin could suppress p65 nuclear translocation, and overexpression of TSP50 reversed the suppressive effect of cardamonin on p65 nuclear translocation. Taken together, these results suggest that cardamonin inhibited cell viability and tumorigenesis at least partially via blocking the activation of TSP50-mediated nuclear factor-kappaB signaling pathway, and cardamonin may be a promising anticancer drug candidate in the development of a novel agent for TSP50 high expressing cancer cells. PMID- 26855341 TI - Development of Pediatric Neurologic Emergency Life Support Course: A Preliminary Report. AB - BACKGROUND: Acute neurological emergencies (ANEs) in children are common life threatening illnesses and are associated with high mortality and severe neurological disability in survivors, if not recognized early and treated appropriately. We describe our experience of teaching a short, novel course "Pediatric Neurologic Emergency Life Support" to pediatricians and trainees in a resource-limited country. METHODS: This course was conducted at 5 academic hospitals from November 2013 to December 2014. It is a hybrid of pediatric advance life support and emergency neurologic life support. This course is designed to increase knowledge and impart practical training on early recognition and timely appropriate treatment in the first hour of children with ANEs. Neuroresuscitation and neuroprotective strategies are key components of this course to prevent and treat secondary injuries. Four cases of ANEs (status epilepticus, nontraumatic coma, raised intracranial pressure, and severe traumatic brain injury) were taught as a case simulation in a stepped-care, protocolized approach based on best clinical practices with emphasis on key points of managements in the first hour. RESULTS: Eleven courses were conducted during the study period. One hundred ninety-six physicians including 19 consultants and 171 residents participated in these courses. The mean (SD) score was 65.15 (13.87%). Seventy percent (132) of participants were passed (passing score > 60%). The overall satisfaction rate was 85%. CONCLUSIONS: Pediatric Neurologic Emergency Life Support was the first-time delivered educational tool to improve outcome of children with ANEs with good achievement and high satisfaction rate of participants. Large number courses are required for future validation. PMID- 26855342 TI - Is It Ovarian Torsion? A Systematic Literature Review and Evaluation of Prediction Signs. AB - OBJECTIVES: This study aimed to identify, through systematic literature review, the most reliable clinical, biological, and radiological signs of ovarian torsion in the pediatric population and to compare their diagnostic value. METHODS: This is a systematic review of the literature, searching MEDLINE, EMBASE, and Cochrane Databases for articles published between January 1990 and January 2014. RESULTS: From the 946 references initially identified, 14 retrospective publications fulfilled the inclusion criteria, involving a total of 663 episodes of ovarian torsion. Sudden onset abdominal pain with nausea and/or vomiting is the most frequent symptom of ovarian torsion. It can occur at any age, not only in menarchal or perimenarchal patients. Abdominal tenderness is present in 88.4% of patients, whereas only 24% have a palpable mass. Blood tests are commonly requested (51.4% of cases) but are not diagnostic. Abnormalities on plain abdominal radiograph include masses, calcifications, and ossified images. Ultrasound has a sensitivity for ovarian torsion of 79% and computerized tomographic scan of 42.2%. There is a significant diagnostic delay at 101.8 hours (median). CONCLUSIONS: Abdominal pain in children and adolescents is difficult to evaluate, and the diagnosis of ovarian torsion remains a challenge. Because of its potential complications, we need effective clinical tools. From our review of the literature, it was not possible to develop a diagnostic algorithm. Further research is needed to improve our practice and shorten the delay to diagnosis. Considering the low incidence of ovarian torsion, a multicenter prospective study would be required. PMID- 26855343 TI - Spontaneous Subclavian Vein Thrombosis in a Healthy Adolescent Cheerleader: A Case of Paget-Schroetter Syndrome. AB - We present the case of a healthy 13-year-old female adolescent who developed acute progressive swelling and pain in her right upper extremity that was secondary to an acute deep venous thrombosis of her right subclavian vein. Dynamic imaging revealed subclavian vein compression at the junction of the first rib and proximal third of the clavicle consistent with Paget-Schroetter syndrome, also known as effort-related thrombosis. The compressive etiology of her thrombus was most likely related to her cheerleading activity, in which she served as the pyramid base. The patient received multimodal therapy including anticoagulation, mechanical and site-directed thrombolysis, and a first rib resection. This case illustrates that frontline providers should have a high index of suspicion for an upper extremity thrombosis in pediatric patients who present with unilateral arm swelling. PMID- 26855344 TI - Urinary Tract Infection and Antimicrobial Stewardship in the Emergency Department. AB - OBJECTIVES: The aims of this study were to assess empiric antibiotic use for presumed urinary tract infection (UTI) in the emergency department (ED) and to determine how often urine culture results subsequently do not confirm the diagnosis. METHODS: This study is a retrospective cohort study of patients aged 21 years or younger in the Nationwide Children's Hospital ED from May 1, 2012, to October 31, 2012, who had a urinalysis and urine culture performed and were discharged home with empiric antibiotic therapy for presumed UTI. Patients with known urinary tract anomaly or antibiotic use in the previous 7 days were excluded. Confirmed UTI was defined as pyuria (>5 white blood cells per high power field or dipstick positive for leukocyte esterase) and a positive urine culture (>=50,000 colony-forming units/mL of a uropathogen). RESULTS: Of the 175 enrolled patients, urine was obtained by clean catch in 138 (79%), catheterization in 35 (20%), first-pass void in 1 (0.6%), and undocumented method in 1 (0.6%). Pyuria was demonstrated in 164 patients (94%), but only 97 (55%) had a positive urine culture. The combination of pyuria and a positive urine culture confirmed UTI in 90 patients (51%). The most commonly prescribed antibiotics were cefdinir in 103 patients (59%), trimethoprim/sulfamethoxazole in 40 (23%), and ciprofloxacin in 23 (13%). The median duration of prescribed therapy was 10 days (interquartile range, 7-10 days). Treatment duration was correlated negatively with age (r = -0.53, P < 0.01). CONCLUSIONS: The current management of suspected UTI in ED patients results in unnecessary antibiotic exposure, highlighting an important opportunity for outpatient antimicrobial stewardship efforts. PMID- 26855345 TI - Multiportal combined transnasal transoral transpharyngeal endoscopic approach for selected skull base cancers. AB - BACKGROUND: Minimally invasive endoscopic endonasal approaches to the ventral skull base have evolved considerably over the past several years. However, where there is a lateral extension of tumors as far as the parapharyngeal spaces with inferior extension below the level of the soft palate, limitations remain for an exclusive transnasal approach. METHODS: A combined endoscopic-assisted transnasal transoral-transpharyngeal multiportal approach was performed to resect selected skull base malignancies that could not be adequately managed using a single approach. RESULTS: Three cases of skull base cancer (squamous cell carcinoma, polymorphous low-grade adenocarcinoma, and high-grade osteosarcoma) were suitable for such an approach. In all cases, a radical resection was obtained without major complications and with minimal morbidity for the patient. CONCLUSION: The transnasal, transoral, and transpharyngeal surgical windows are complementary approaches that, when combined, provide excellent exposure for selected skull base malignancies that have extended too laterally and inferiorly to allow an exclusively transnasal approach. (c) 2016 Wiley Periodicals, Head Neck 38: E2440 E2445, 2016. PMID- 26855346 TI - Molecular characterization of enterohemorrhagic Escherichia coli hemolysin gene (EHEC-hlyA)-harboring isolates from cattle reveals a diverse origin and hybrid diarrheagenic strains. AB - In the present study we investigated the occurrence of Escherichia coli strains harboring the gene encoding enterohemorrhagic E. coli hemolysin (EHEC-HlyA) in cattle and the association of this gene with various diarrheagenic E. coli (DEC) pathotypes. First, the bovine E. coli isolates were screened for EHEC-hlyA gene by PCR, and then they were characterized for the phylogenetic groups and the presence of the major virulence genes of different DEC pathotypes. In total, 25 virulence gene profiles were observed in 54 EHEC-hlyA+ isolates that reflect a considerable heterogeneity. The EHEC-hlyA+ strains were mostly associated with EHEC (72%), while only 7.4% were enteropathogenic E. coli (EPEC). We also showed the presence of estA gene of enterotoxigenic E. coli (ETEC) in 6 isolates (11.1%). Interestingly, two of the estA+ strains showed hybrid pathotypes with one carrying eae/estA (EPEC/ETEC), and the other one stx2/astA/estA (EHEC/ETEC). None of the isolates were related to enteroaggregative E. coli (EAggEC), enteroinvasive E. coli (EIEC), and necrotoxigenic E. coli (NTEC). The EHEC plasmid encoded genes occurred in seven different combinations with EHEC hlyA/saa/subA/espP being the most prevalent (46.3%). All stx-/eae+ strains carried O island 57 (OI-57) molecular marker(s) that may indicate these to be the progenitors of EHEC or strains losing stx. The most prevalent phylogroup was B1 (61.1%), but the most heterogeneous strains including the hybrid strains belonged to A phylogroup. Overall, our results indicate that cattle EHEC-hlyA encoding E. coli isolates consist of diverse diarrheagenic strains with the possible existence of hybrid pathotypes. Future studies are required to clarify the evolutionary aspects and clinical significance of these strains in humans and domestic animals. PMID- 26855348 TI - How Low Can You Go?: Implications of the Systolic Blood Pressure Intervention Trial for Hypertension Management. PMID- 26855349 TI - Biomaterial-Stabilized Soft Tissue Healing for Healing of Critical-Sized Bone Defects: the Masquelet Technique. AB - Critical-sized bone defects present a significant burden to the medical community due to their challenging treatment. However, a successful limb-salvaging technique, the Masquelet Technique (MT), has significantly improved the prognosis of many segmental bone defects in helping to restore form and function. Although the Masquelet Technique has proven to be clinically effective, the physiology of the healing it induces is not well understood. Multiple modifiable factors have been implicated by various surgical and research teams, but no single factor has been proven to be critical to the success of the Masquelet Technique. In this review the most recent clinical and experimental evidence that supports and helps to decipher the traditional Masquelet, as well as the modifiable factors and their effect on the success of the technique are discussed. In addition, future developments for the integration of the traditional Masquelet Technique with the use of alternative biomaterials to increase the effectiveness and expand the clinical applicability of the Masquelet Technique are reviewed. PMID- 26855350 TI - The impact of skin decontamination on the time window for effective treatment of percutaneous VX exposure. AB - The main goal of the present study was to obtain insight into depot formation and penetration following percutaneous VX poisoning, in order to identify an appropriate decontamination window that can enhance or support medical countermeasures. The study was executed in two phases, using the hairless guinea pig as an animal model. In the first phase the effect of various decontamination regimens on levels of free VX in skin and plasma were studied as well as on blood cholinesterase levels. Animals were exposed to 0.5 mg/kg VX and were not decontaminated (control), decontaminated with RSDL once at 15 or 90 min after exposure or three times at 15, 25 and 35 (10-min interval) or 15, 45 and 75 min after exposure (30-min interval). There was no significant effect of any of the decontamination regimens on the 6-h survival rate of the animals. However, all animals that had been decontaminated 15 min after exposure, showed a survival rate of more than 90%, compared to 50-60% in animals that were not decontaminated or decontaminated at 90 min after exposure. In the second phase of the study, hairless guinea pigs were exposed to 1 mg/kg VX on the shoulder, followed either by decontamination with RSDL (10 min interval), conventional treatment on indication of clinical signs or a combination thereof. It appeared that a thorough, repeated decontamination alone could not save the majority of the animals. A 100% survival rate was observed in the group that received a combination of decontamination and treatment. In conclusion, the effects of VX exposure could be influenced by various RSDL decontamination regimens. The results in freely moving animals showed that skin decontamination, although not fully effective in removing all VX from the skin and skin depot is crucial to support pharmacological intervention. PMID- 26855351 TI - Gut microbiota and the pathogenesis of necrotizing enterocolitis in preterm neonates. AB - Necrotizing enterocolitis (NEC) remains a devastating intestinal disease in preterm neonates. In this population, disruption of the gut microbiota development, mainly due to organ immaturity, antibiotic use and hospital microbial environment, plays a key role in the pathogenesis of NEC. This gut dysbiosis has been associated with opportunistic pathogens overgrowth, expression of virulence factors, altered metabolic functions and inflammatory dysregulated responses. In this review, we provide an updated summary of the host and gut microbiota interactions during the formative early life. We also explore the key determinants of gut dysbiosis in preterm neonates with NEC. Finally, we discuss the promising role of bacteriotherapy in the management of NEC, the aim being to shape or restore the beneficial gut bacterial communities. PMID- 26855352 TI - Quantifying enhancement in aerosol radiative forcing during 'extreme aerosol days' in summer at Delhi National Capital Region, India. AB - Changes in aerosol characteristics (spectral aerosol optical depth, AOD and composition) are examined during the transition from 'relatively clean' to 'extreme' aerosol days in the summer of 2012 at Delhi National Capital Region (NCR), India. AOD smaller than 0.54 (i.e. 12-year mean AOD-1sigma) represents 'relatively clean' days in Delhi during the summer. 'Extreme' days are defined by the condition when AOD0.5 exceeds 12-year mean AOD+1 standard deviation (sigma). Mean (+/-1sigma) AOD increases to 1.2+/-0.12 along with a decrease of Angstrom Exponent from 0.54+/-0.09 to 0.22+/-0.12 during the 'extreme' days. Aerosol composition is inferred by fixing the number concentrations of various individual species through iterative tweaking when simulated (following Mie theory) AOD spectrum matches with the measured one. Contribution of coarse mode dust to aerosol mass increased from 76.8% (relatively clean) to 96.8% (extreme events), while the corresponding contributions to AOD0.5 increased from 35.0% to 70.8%. Spectrally increasing single scattering albedo (SSA) and CALIPSO aerosol sub-type information support the dominant presence of dust during the 'extreme' aerosol days. Aerosol direct radiative forcing (ADRF) at the top-of-the-atmosphere increases from 21.2Wm(-2) (relatively clean) to 56.6Wm(-2) (extreme), while the corresponding change in surface ADRF is from -99.5Wm(-2) to -153.5Wm(-2). Coarse mode dust contributes 60.3% of the observed surface ADRF during the 'extreme' days. On the contrary, 0.4% mass fraction of black carbon (BC) translates into 13.1% contribution to AOD0.5 and 33.5% to surface ADRF during the 'extreme' days. The atmospheric heating rate increased by 75.1% from 1.7K/day to 2.96K/day during the 'extreme' days. PMID- 26855353 TI - Pesticide knowledge and practice among horticultural workers in the Lam Dong region, Vietnam: A case study of chrysanthemum and strawberries. AB - BACKGROUND: In Vietnam, large amounts of pesticides are being used in agriculture. Next to benefits for agriculture, pesticides impose a huge threat to the environment when they are used in the wrong way. The objective of this work was to determine the level of knowledge and awareness of the smallholder farmers towards the use of pesticides in Vietnam, Da Lat region. Based on the collected data, an occupational and environmental risk assessment was performed. RESULTS: The results indicate that the majority of the pesticide operators in the strawberry and chrysanthemum crops have a rather high education. Pesticide knowledge, on the other hand, is usually gained through experience with pests and diseases. Only 30% of the farmers consulted a pesticide specialist or government stewardship for information on (new) pesticide products. Pesticide usage is rather high with application frequencies up to once every three days during the wet season. Pesticide packages are stored to be incinerated (51%) or to be thrown away with the garbage/taken to the landfill (37%). Only a small percentage disposes the packages into the local river (2%). The use of personal protection equipment is well established. Occupational risk assessment showed that the re entry worker is exposed to a high risk. CONCLUSION: While a general awareness of the hazard of pesticides to human health and the environment is present, practical implementation of this awareness, however, is still limited in strawberry and chrysanthemum crop. The environmental risk evaluation indicated plant protection products of which the use should be limited. PMID- 26855354 TI - Investigation of spatial and historical variations of air pollution around an industrial region using trace and macro elements in tree components. AB - Several trace and macro elements (n=48) were measured in pine needle, branch, bark, tree ring, litter, and soil samples collected at 27 sites (21 industrial, 6 background) to investigate their spatial and historical variation in Aliaga industrial region in Turkey. Concentrations generally decreased with distance from the sources and the lowest ones were measured at background sites far from major sources. Spatial distribution of anthropogenic trace elements indicated that their major sources in the region are the iron-steel plants, ship-breaking activities and the petroleum refinery. Patterns of 40 elements that were detected in most of the samples were also evaluated to assess their suitability for investigation of historical variations. Observed increasing trends of several trace and macro elements (As, Cr, Fe, Mo, Ni, V, Cu, Pb, Sb, Sn, and Hg) in the tree-ring samples were representative for the variations in anthropogenic emissions and resulting atmospheric concentrations in Aliaga region. It was shown that lanthanides (La, Ce, Pr, Nd, Sm, Gd, Dy, Er, Yb) could also be used for the investigation of historical variations due to specific industrial emissions (i.e., petroleum refining). Results of the present study showed that tree components, litter, and soil could be used to determine the spatial variations of atmospheric pollution in a region while tree rings could be used to assess the historical variations. PMID- 26855355 TI - Implementation of the effects of physicochemical properties on the foliar penetration of pesticides and its potential for estimating pesticide volatilization from plants. AB - Volatilization from plant foliage is known to have a great contribution to pesticide emission to the atmosphere. However, its estimation is still difficult because of our poor understanding of processes occurring at the leaf surface. A compartmental approach for dissipation processes of pesticides applied on the leaf surface was developed on the base of experimental study performed under controlled conditions using laboratory volatilization chamber. This approach was combined with physicochemical properties of pesticides and was implemented in SURFATM-Pesticides model in order to predict pesticide volatilization from plants in a more mechanistic way. The new version of SURFATM-Pesticide model takes into account the effect of formulation on volatilization and leaf penetration. The model was evaluated in terms of 3 pesticides applied on plants at the field scale (chlorothalonil, fenpropidin and parathion) which display a wide range of volatilization rates. The comparison of modeled volatilization fluxes with measured ones shows an overall good agreement for the three tested compounds. Furthermore the model confirms the considerable effect of the formulation on the rate of the decline in volatilization fluxes especially for systemic products. However, due to the lack of published information on the substances in the formulations, factors accounting for the effect of formulation are described empirically. A sensitivity analysis shows that in addition to vapor pressure, the octanol-water partition coefficient represents important physicochemical properties of pesticides affecting pesticide volatilization from plants. Finally the new version of SURFATM-Pesticides is a prospecting tool for key processes involved in the description of pesticide volatilization from plants. PMID- 26855356 TI - The direct impact of landslides on household income in tropical regions: A case study from the Rwenzori Mountains in Uganda. AB - Landslides affect millions of people worldwide, but theoretical and empirical studies on the impact of landslides remain scarce, especially in Sub-Saharan Africa. This study proposes and applies a method to estimate the direct impact of landslides on household income and to investigate the presence of specific risk sharing and mitigation strategies towards landslides in a tropical and rural environment. An original cross-sectional household survey is used in combination with geographical data to acquire detailed information on livelihoods and on hazards in the Rwenzori mountains, Uganda. Ordinary least square regressions and probit estimations with village fixed effects are used to estimate the impact of landslides and the presence of mitigation strategies. Geographical information at household level allows to disentangle the direct impact from the indirect effects of landslides. We show that the income of affected households is substantially reduced during the first years after a landslide has occurred. We find that members of recently affected households participate more in wage-employment or in self-employed activities, presumably to address income losses following a landslide. Yet, we see that these jobs do not provide sufficient revenue to compensate for the loss of income from agriculture. Given that landslides cause localized shocks, finding a significant direct impact in our study indicates that no adequate risk sharing mechanisms are in place in the Rwenzori sub-region. These insights are used to derive policy recommendations for alleviating the impact of landslides in the region. By quantifying the direct impact of landslides on household income in an agricultural context in Africa this study draws the attention towards a problem that has been broadly underestimated so far and provides a sound scientific base for disaster risk reduction in the region. Both the methodology and the findings of this research are applicable to other tropical regions with high landslide densities. PMID- 26855357 TI - Stationary and transient thermal states of barometric pumping in the access pit of an underground quarry. AB - The transition zone between free and underground atmospheres hosts spectacular phenomena, as demonstrated by temperature measurements performed in the 4.6m diameter and 20m deep vertical access pit of an abandoned underground quarry located in Vincennes, near Paris. In summer, a stable stratification of the atmosphere is maintained, with coherent temperature variations associated with atmospheric pressure changes, with a barometric tide S2 larger than 0.1 degrees C peak to peak. When the winter regime of turbulent cold air avalanches is initiated, stratification with pressure induced signals can be restored transiently in the upper part of the pit, while the lower part remains fully mixed and insensitive to pressure variations. The amplitude of the pressure to temperature transfer function increases with frequency below 5*10(-4)Hz, with values at 3*10(-5)Hz varying from 0.1 degrees C.hPa(-1) at the bottom up to 2 degrees C.hPa(-1) towards the top of the pit. These temperature variations are accounted for by cave breathing, which is pressure induced motion of air amplified by the large volume of the quarry. This understanding is supported by a numerical model including advective heat transport, heat diffusion, and heat exchange with the pit walls. Mean lifetime in the pit is of the order of 9 to 13h, and barometric pumping results in an effective ventilation rate of the quarry of the order of 10(-7)s(-1). This study illustrates the important role of barometric pumping in heat and matter transport between atmosphere and lithosphere. The resulting stationary and transient states, revealed in this pit, are probably a general feature of functioning interface systems, and therefore are an important aspect to consider in problems of contaminant transport, or the preservation of precious heritage such as rare ecosystems or painted caves. PMID- 26855358 TI - Corrigendum: Efficacy of Concurrent Chemotherapy for Intermediate Risk NPC in the Intensity-Modulated Radiotherapy Era: a Propensity-Matched Analysis. PMID- 26855359 TI - Increased performance of hydrogen production in microbial electrolysis cells under alkaline conditions. AB - This work reports the first successful enrichment and operation of alkaline bioelectrochemical systems (microbial fuel cells, MFC, and microbial electrolysis cells, MEC). Alkaline (pH=9.3) bioelectrochemical hydrogen production presented better performance (+117%) compared to conventional neutral conditions (2.6 vs 1.2 litres of hydrogen gas per litre of reactor per day, LH2.L(-1)REACTOR.d(-1)). Pyrosequencing results of the anodic biofilm showed that while Geobacter was mainly detected under conventional neutral conditions, Geoalkalibacter sp. was highly detected in the alkaline MFC (21%) and MEC (48%). This is the first report of a high enrichment of Geoalkalibacter from an anaerobic mixed culture using alkaline conditions in an MEC. Moreover, Alkalibacter sp. was highly present in the anodic biofilm of the alkaline MFC (37%), which would indicate its potentiality as a new exoelectrogen. PMID- 26855360 TI - Label-free monitoring of DNA methyltransferase activity based on terminal deoxynucleotidyl transferase using a thioflavin T probe. AB - We have developed a new methodology for fluorescence turn-on detection of DNA methyltransferase (MTase) activity based on terminal deoxynucleotidyl transferase (TdT) using a thioflavin T probe. This method is highly selective and sensitive. The fluorescence intensity was direct proportion to Dam MTase concentration in the range from 0.1 to 8.0 U/mL with a detection limit of 0.1 U/mL. And because no labeling with a fluorophore-quencher pair was required, it is simple and low cost. We envision that our novel fluorescent detection method for Dam MTase activity could be applied as a useful tool in biomedical research. PMID- 26855361 TI - A validated LC-MS/MS method for the sensitive quantitation of serum 7alpha hydroxy-, 7beta hydroxy- and 7keto-dehydroepiandrosterone using a novel derivatization reagent. AB - 7alpha hydroxy-, 7beta hydroxy- and 7keto-dehydroepiandrosterone (7alpha OH-DHEA, 7beta OH-DHEA and 7 oxo-DHEA) are oxidized metabolites of dehydroepiandrosterone (DHEA). Their concentrations are low in the circulation, especially in postmenopausal women, thus resulting in a considerable challenge for their reliable measurement. A sensitive and accurate LC-MS/MS method has been developed using a simple sample preparation procedure and a novel derivatization with 1 amino-4-methyl piperazine (MP). The derivatized metabolites are stable in high water content reagents. A 10 pg/mL (0.2 pg on column) for the low limit of quantitation (LLOQ) has been achieved for all three compounds. A proper choice of multiple reaction monitoring (MRM) transitions provides good specificity. The excess amount of reagent can be removed from the sample during the derivatization process. Within the calibration range of 10-2000 pg/mL, a good linearity was obtained with R>0.99 where the weighing factor is 1/X while the bias and coefficient of variance (CV) are within 8% for all levels of QCs and calibration curves. This method has been fully validated according to the FDA guidelines, where the results of the matrix effect meet the acceptance criteria while freeze thaw stability, short and long term stability in matrix and solution as well as post-processed sample stability meet the requirements. With this method, the concentrations of 7alpha OH-DHEA, 7beta OH-DHEA and 7 oxo-DHEA were measured in premenopausal and postmenopausal serum. The average concentration of 7alpha OH DHEA is equivalent to that of 7beta OH-DHEA in both types of sera. PMID- 26855362 TI - Sensory and optogenetically driven single-vessel fMRI. AB - Magnetic resonance imaging (MRI) sensitivity approaches vessel specificity. We developed a single-vessel functional MRI (fMRI) method to image the contribution of vascular components to blood oxygenation level-dependent (BOLD) and cerebral blood volume (CBV) fMRI signal. We mapped individual vessels penetrating the rat somatosensory cortex with 100-ms temporal resolution by MRI with sensory or optogenetic stimulation. The BOLD signal originated primarily from venules, and the CBV signal from arterioles. The single-vessel fMRI method and its combination with optogenetics provide a platform for mapping the hemodynamic signal through the neurovascular network with specificity at the level of individual arterioles and venules. PMID- 26855363 TI - epiGBS: reference-free reduced representation bisulfite sequencing. AB - We describe epiGBS, a reduced representation bisulfite sequencing method for cost effective exploration and comparative analysis of DNA methylation and genetic variation in hundreds of samples de novo. This method uses genotyping by sequencing of bisulfite-converted DNA followed by reliable de novo reference construction, mapping, variant calling, and distinction of single-nucleotide polymorphisms (SNPs) versus methylation variation (software is available at https://github.com/thomasvangurp/epiGBS). The output can be loaded directly into a genome browser for visualization and into RnBeads for analysis of differential methylation. PMID- 26855365 TI - A role for ATP-sensitive potassium channels in the anticonvulsant effects of triamterene in mice. AB - There are reports indicating that diuretics including chlorothiazide, furosemide, ethacrynic acid, amiloride and bumetanide can have anticonvulsant properties. Intracellular acidification appears to be a mechanism for the anticonvulsant action of some diuretics. This study was conducted to investigate whether or not triamterene, a K(+)-sparing diuretic, can generate protection against seizures induced by intravenous or intraperitoneal pentylenetetrazole (PTZ) models. And to see if, triamterene can withstand maximal electroshock seizure (MES) in mice. We also investigated to see if there is any connection between triamterene's anti seizure effect and ATP-sensitive K(+) (KATP) channels. Five days triamterene oral administration (10, 20 and 40 mg/kg), significantly increased clonic seizure threshold which was induced by intravenous pentylenetetrazole. Triamterene (10, 20 and 40 mg/kg) treatment also increased the latency of clonic seizure and decreased its frequency in intraperitoneal PTZ model. Administration of triamterene (20 mg/kg) also decreased the incidence of tonic seizure in MES induced seizure. Co-administration of a KATP sensitive channel blocker, glibenclamide, in the 6th day, 60 min before intravenous PTZ blocked triamterene's anticonvulsant effect. A KATP sensitive channel opener, diazoxide, enhanced triamterene's anti-seizure effect in both intravenous PTZ or MES seizure models. At the end, triamterene exerts anticonvulsant effect in 3 seizure models of mice including intravenous PTZ, intraperitoneal PTZ and MES. The anti-seizure effect of triamterene probably is induced through KATP channels. PMID- 26855364 TI - Oestrogen promotes healing in a bacterial LPS model of delayed cutaneous wound repair. AB - Wound infection is a major clinical problem, yet understanding of bacterial host interactions in the skin remains limited. Microbe-derived molecules, known as pathogen-associated molecular patterns, are recognised in barrier tissues by pattern-recognition receptors. In particular, the pathogen-associated molecular pattern, lipopolysaccharide (LPS), a component of microbial cell walls and a specific ligand for Toll-like receptor 4, has been widely used to mimic systemic and local infection across a range of tissues. Here we administered LPS derived from Klebsiella pneumoniae, a species of bacteria that is emerging as a wound associated pathogen, to full-thickness cutaneous wounds in C57/BL6 mice. Early in healing, LPS-treated wounds displayed increased local apoptosis and reduced proliferation. Subsequent healing progression was delayed with reduced re epithelialisation, increased proliferation, a heightened inflammatory response and perturbed wound matrix deposition. Our group and others have previously demonstrated the beneficial effects of 17beta-estradiol treatment across a range of preclinical wound models. Here we asked whether oestrogen would effectively promote healing in our LPS bacterial infection model. Intriguingly, co-treatment with 17beta-estradiol was able to promote re-epithelialisation, dampen inflammation and induce collagen deposition in our LPS-delayed healing model. Collectively, these studies validate K. pneumoniae-derived LPS treatment as a simple yet effective model of bacterial wound infection, while providing the first indication that oestrogen could promote cutaneous healing in the presence of infection, further strengthening the case for its therapeutic use. PMID- 26855366 TI - A screening tool to identify surgical candidates with drug refractory epilepsy in a resource limited settings. AB - OBJECTIVES: Access to epilepsy surgery remains a considerable challenge in contemporary healthcare systems. Given the limitations in resources and demand for Epilepsy Monitoring Unit (EMU) assessments, information that can be used to expedite the process is of great value. The purpose of this study was to identify variables prior to EMU admission that may be associated with candidacy for prospective epilepsy surgery. METHODS: This was a prospective study conducted at the Department of Neurology, All India Institute of Medical Sciences, New Delhi, India. We identified two subgroups of patients from 501 drug refractory epilepsy (DRE) patients admitted in EMU of Neurology Department, AIIMS from 2006 onwards following validation of proposed tool in 40 patients. They on subsequent investigations were either cleared or not cleared for epilepsy surgery. A tool consisting of variables likely to predict surgical candidacy in persons with DRE in Indian settings was developed for identification of patients who might benefit from an early epilepsy surgery evaluation. RESULTS: Statistical analysis revealed significant differences between the two groups for several variables. Non surgical candidates had non-disabling seizures, seizures improved with a combination of drugs, had little/no AEDs side effects and had near normal or normal scalp EEG and MRI brain. SIGNIFICANCE: Using the best available evidence, we developed a decision making tool which can provide a comprehensive quick guide for determining candidacy for epilepsy surgery evaluations in resource limited settings. Given the demand for EMU assessments, information that can be used to expedite the process is of value. PMID- 26855367 TI - Regionalization of Pediatric Surgery: Trends Already Underway. AB - INTRODUCTION: This study aims to characterize the delivery of pediatric surgical care based on hospital volume stratified by disease severity, geography, and specialty. Longitudinal regionalization over the 10-year study period is noted and further explored. METHODS: The Kids' Inpatient Database (KID) was queried from 2000 to 2009 for patients <18 years undergoing noncardiac surgery. Hospitals nationwide were grouped into commutable regions and identified as high-volume centers (HVCs) if they had more than 1000 weighted procedures per year. Regions that had at least one HVC and one or more additional lower volume center were included for analysis. Low-risk, high-risk neonatal, and surgical subspecialties were analyzed separately. RESULTS: A total of 385,242 weighted pediatric surgical admissions in 33 geographical regions and 224 hospitals were analyzed. Overall, HVCs comprised 33 (14.7%) hospitals, medium-volume center (MVC) 33 (14.7%), and low-volume center (LVC) 158 (70.5%). The four low-risk procedures analyzed were increasingly regionalized: appendectomy (52% in HVCs in 2000 to 60% in 2009, P < 0.001), fracture reduction (63% to 68%, P < 0.001), cholecystectomy (54% to 63%, P < 0.001), and pyloromyotomy (65% to 85%, P < 0.001). Neonatal surgery showed significant regionalization trends for tracheoesophageal fistula (66% to 87%, P < 0.001) and gastroschisis (76% to 89%, P < 0.001). CONCLUSIONS: This is the first large-scale, multi-region analysis to demonstrate that pediatric surgical care has transitioned to HVCs over a recent decade, particularly for low-risk patients. It is important for practitioners and policymakers alike to understand such volume trends in order to ensure hospital capacity while maintaining an optimal quality of care. PMID- 26855368 TI - Factors Associated with Abnormal Imaging and Infection Recurrence after a First Febrile Urinary Tract Infection in Children. AB - Introduction We determined factors associated with abnormal imaging and recurrent infections after a first febrile urinary tract infection (UTI) in children younger than 3 years. Materials and Methods We retrospectively reviewed the records of all patients treated at our institute during the years 2000-2009, for a first febrile UTI in children younger than 3 years, who underwent ultrasonography and voiding cystourethrography. We evaluated data regarding factors potentially associated with abnormal ultrasonography and voiding cystourethrography results and recurrence of infections, and formulated a risk score system to assess risk of reflux and high-grade reflux. Results There were 282 patients. The only factor predicting abnormal ultrasonogram was non Escherichia coli infection. Risk factors for vesicoureteral reflux included abnormal ultrasonogram, atypical infection, non-E. coli infection and infection recurrence. Patients with no identified risk factors for vesicoureteral reflux were unlikely to have high-grade reflux. Higher risk scores were associated with a higher risk for reflux. Non-E. coli infection was the only statistically significant predictor of infection recurrence. Conclusion All children younger than 3 years with first febrile UTI should undergo ultrasonography. Thereafter, patients with no predictive factors for vesicoureteral reflux may be followed up without further imaging. A non-E. coli infection is associated with reflux and infection recurrence. PMID- 26855370 TI - The effect of cellular isolation and cryopreservation on the expression of markers identifying subsets of regulatory T cells. AB - BACKGROUND: The role of CD4(+) regulatory T cells (Tregs) and their subsets during HIV infection is controversial. Cryopreserved peripheral blood mononuclear cells (PBMC) are an important source for assessing number and function of Tregs. However, it is unknown if PBMC isolation and cryopreservation affect the expression of CD120b and CD39, markers that identify specific subsets of Tregs. METHODS: HIV-uninfected (HIV-) and -infected (HIV+) men were randomly selected from the Multicenter AIDS Cohort Study (MACS). Percentages of CD120b(+) and CD39(+) Tregs measured by flow cytometry in whole blood and in corresponding fresh and cryopreserved PBMC were compared. RESULTS: Percentages of CD120b(+) Tregs were significantly lower in a) fresh PBMC relative to whole blood, and b) freshly thawed frozen PBMC relative to fresh PBMC when the recovery of viable cryopreserved cells was low. When present, low expression of CD120b in frozen PBMC was reversible by 4h of in vitro culture. In contrast, expression of CD39 on Tregs was not affected by isolation and/or cryopreservation of PBMC, or by relative recovery of cryopreserved PBMC. These findings were unaffected by the HIV status of the donor. CONCLUSION: The data suggest that percentages of CD120b(+) Tregs and CD39(+) Tregs can be validly measured in either whole blood or PBMC (fresh and frozen) in HIV- and HIV+ men. However, for measurement of CD120b(+) Tregs one type of sample should be used consistently within a given study, and thawed frozen cells may require in vitro culture if recovery of viable cells is low. PMID- 26855371 TI - The effect of communication and implicit associations on consuming insects: An experiment in Denmark and Italy. AB - It has been widely noted that the introduction of insects in Westerns' diet might be a promising path towards a more sustainable food consumption. However, Westerns' are almost disgusted and sceptical about the eating of insects. In the current paper we report the results of an experiment conducted in two European countries-Denmark and Italy-different for food culture and familiarity with the topic of eating insects. We investigated the possibility to foster people's willingness to eat insect-based food through communication, also comparing messages based on individual vs. societal benefits of the eating of insects. Communication proved to be effective on intention and behaviour, and the societal message appeared to be more robust over time. The communication effect is significant across nation, gender, and previous knowledge about the topic. In addition, we investigated the impact of non-conscious negative associations with insects on the choice to eat vs. not eat insect-based food. Implicit attitudes proved to be a powerful factor in relation to behaviour, yet they did not impede the effectiveness of communication. PMID- 26855372 TI - Failure of tooth eruption and brachydactyly in pseudohypoparathyroidism are not related to plasma parathyroid hormone-related protein levels. AB - BACKGROUND: Pseudohypoparathyroidism (PHP) is a genetic disorder characterized by resistance to the peripheral action of PTH due to maternally inherited heterozygous inactivating mutations in the coding sequence of Gsalpha or intronic regions of GNAS leading to aberrant splice variants (PHP1A), or methylation defects at GNAS (PHP1B). Brachydactyly is a clinical feature associated with both PHP1A and PHP1B, although it is more frequent in PHP1A patients. Loss-of-function mutations in PTHLH, the gene coding for parathyroid hormone related protein (PTHrP) were previously described in some patients with brachydactyly. Primary failure of tooth eruption (PFE) is related to some syndromes involving skeletal development, but it is also known as a nonsyndromic autosomal dominant condition. Previous studies showed that familial nonsyndromic PFE is caused by heterozygous mutations in the gene encoding the G protein-coupled receptor (PTH1R) for PTH and PTHrP. Thus, we hypothesized that PTHrP resistance could result in failure of tooth eruption (FTE) and/or brachydactyly in PHP. SUBJECTS AND METHODS: Nineteen patients with a molecular diagnosis of PHP underwent dental panoramic radiography (DPR), hand radiography and had their PTHrP levels measured. Patients with alterations at DPR were submitted to clinical dental evaluation. RESULTS: Nine patients had FTE and 7 patients had brachydactyly; 4 patients presented both features and none of them presented high PTHrP levels. Fourteen patients had PTHrP levels within the normal range and only one patient had slightly elevated PTHrP levels. Additionally, three novel GNAS mutations were described. CONCLUSION: We described the dental abnormalities in a large series of PHP patients that were followed in a single tertiary center. No relationship between plasma PTHrP levels and failure of tooth eruption, dental manifestations of PHP or brachydactyly was found. It is important that doctors pay attention to dental manifestations of the disease in order to refer patients to a proper care with dentists. PMID- 26855369 TI - Hippocampal neurogenesis: Learning to remember. AB - Alzheimer's disease, the most prevalent form of dementia in the elderly, is characterized by progressive memory loss and cognitive dysfunction. It has become increasingly clear that while neuronal cell loss in the entorhinal cortex and hippocampus occurs in Alzheimer's disease, it is preceded by a long period of deficits in the connectivity of the hippocampal formation that contributes to the vulnerability of these circuits. Hippocampal neurogenesis plays a role in the maintenance and function of the dentate gyrus and hippocampal circuitry. This review will examine the evidence suggesting that hippocampal neurogenesis plays a role in cognitive function that is affected in Alzheimer's disease, will discuss the cognitive assessments used for the detection of Alzheimer's disease in humans and rodent models of familial Alzheimer's disease, and their value for unraveling the mechanism underlying the development of cognitive impairments and dementia. PMID- 26855373 TI - Fructose consumption does not worsen bone deficits resulting from high-fat feeding in young male rats. AB - Dietary-induced obesity (DIO) resulting from high-fat (HF) or high-sugar diets produces a host of deleterious metabolic consequences including adverse bone development. We compared the effects of feeding standard rodent chow (Control), a 30% moderately HF (starch-based/sugar-free) diet, or a combined 30%/40% HF/high fructose (HF/F) diet for 12weeks on cancellous/cortical bone development in male Sprague-Dawley rats aged 8weeks. Both HF feeding regimens reduced the lean/fat mass ratio, elevated circulating leptin, and reduced serum total antioxidant capacity (tAOC) when compared with Controls. Distal femur cancellous bone mineral density (BMD) was 23-34% lower in both HF groups (p<0.001) and was characterized by lower cancellous bone volume (BV/TV, p<0.01), lower trabecular number (Tb.N, p<0.001), and increased trabecular separation versus Controls (p<0.001). Cancellous BMD, BV/TV, and Tb.N were negatively associated with leptin and positively associated with tAOC at the distal femur. Similar cancellous bone deficits were observed at the proximal tibia, along with increased bone marrow adipocyte density (p<0.05), which was negatively associated with BV/TV and Tb.N. HF/F animals also exhibited lower osteoblast surface and reduced circulating osteocalcin (p<0.05). Cortical thickness (p<0.01) and tissue mineral density (p<0.05) were higher in both HF-fed groups versus Controls, while whole bone biomechanical characteristics were not different among groups. These results demonstrate that "westernized" HF diets worsen cancellous, but not cortical, bone parameters in skeletally-immature male rats and that fructose incorporation into HF diets does not exacerbate bone loss. In addition, they suggest that leptin and/or oxidative stress may influence DIO-induced alterations in adolescent bone development. PMID- 26855375 TI - Polydopamine Inter-Fiber Networks: New Strategy for Producing Rigid, Sticky, 3D Fluffy Electrospun Fibrous Polycaprolactone Sponges. AB - Designing versatile 3D interfaces that can precisely represent a biological environment is a prerequisite for the creation of artificial tissue structures. To this end, electrospun fibrous sponges, precisely mimicking an extracellular matrix and providing highly porous interfaces, have capabilities that can function as versatile physical cues to regenerate various tissues. However, their intrinsic features, such as sheet-like, thin, and weak structures, limit the design of a number of uses in tissue engineering applications. Herein, a highly facile methodology capable of fabricating rigid, sticky, spatially expanded fluffy electrospun fibrous sponges is proposed. A bio-inspired adhesive material, poly(dopamine) (pDA), is employed as a key mediator to provide rigidity and stickiness to the 3D poly(epsilon-caprolactone) (PCL) fibrous sponges, which are fabricated using a coaxial electrospinning with polystyrene followed by a selective leaching process. The iron ion induced oxidation of dopamine into pDA networks interwoven with PCL fibers results in significant increases in the rigidity of 3D fibrous sponges. Furthermore, the exposure of catecholamine groups on the fiber surfaces promotes the stable attachment of the sponges on wet organ surfaces and triggers the robust immobilization of biomolecules (e.g., proteins and gene vectors), demonstrating their potential for 3D scaffolds as well as drug delivery vehicles. Because fibrous structures are ubiquitous in the human body, these rigid, sticky, 3D fibrous sponges are good candidates for powerful biomaterial systems that functionally mimic a variety of tissue structures. PMID- 26855374 TI - Combined exposure to big endothelin-1 and mechanical loading in bovine sternal cores promotes osteogenesis. AB - Increased bone formation resulting from mechanical loading is well documented; however, the interactions of the mechanotransduction pathways are less well understood. Endothelin-1, a ubiquitous autocrine/paracrine signaling molecule promotes osteogenesis in metastatic disease. In the present study, it was hypothesized that exposure to big endothelin-1 (big ET1) and/or mechanical loading would promote osteogenesis in ex vivo trabecular bone cores. In a 2*2 factorial trial of daily mechanical loading (-2000MUepsilon, 120cycles daily, "jump" waveform) and big ET1 (25ng/mL), 48 bovine sternal trabecular bone cores were maintained in bioreactor chambers for 23days. The bone cores' response to the treatment stimuli was assessed with percent change in core apparent elastic modulus (DeltaEapp), static and dynamic histomorphometry, and prostaglandin E2 (PGE2) secretion. Two-way ANOVA with a post hoc Fisher's LSD test found no significant treatment effects on DeltaEapp (p=0.25 and 0.51 for load and big ET1, respectively). The DeltaEapp in the "no load + big ET1" (CE, 13+/-12.2%, p=0.56), "load + no big ET1" (LC, 17+/-3.9%, p=0.14) and "load + big ET1" (LE, 19+/-4.2%, p=0.13) treatment groups were not statistically different than the control group (CC, 3.3%+/-8.6%). Mineralizing surface (MS/BS), mineral apposition (MAR) and bone formation rates (BFR/BS) were significantly greater in LE than CC (p=0.037, 0.0040 and 0.019, respectively). While the histological bone formation markers in LC trended to be greater than CC (p=0.055, 0.11 and 0.074, respectively) there was no difference between CE and CC (p=0.61, 0.50 and 0.72, respectively). Cores in LE and LC had more than 50% greater MS/BS (p=0.037, p=0.055 respectively) and MAR (p=0.0040, p=0.11 respectively) than CC. The BFR/BS was more than two times greater in LE (p=0.019) and LC (p=0.074) than CC. The PGE2 levels were elevated at 8days post-osteotomy in all groups and the treatment groups remained elevated compared to the CC group on days 15, 19 and 23. The data suggest that combined exposure to big ET1 and mechanical loading results in increased osteogenesis as measured in biomechanical, histomorphometric and biochemical responses. PMID- 26855376 TI - Chemotherapy for advanced non-pancreatic well-differentiated neuroendocrine tumours of the gastrointestinal tract, a systematic review and meta-analysis: A lost cause? AB - BACKGROUND: Chemotherapy is well-established in the treatment of patients with well-differentiated neuroendocrine tumours (NETs) arising from the pancreas (pNETs); however, its role in patients with gastrointestinal non-pancreatic NETs (non-pNETs) is uncertain. This systematic review assesses the evidence for the role of chemotherapy in well-differentiated non-pNET patients. METHODS: Eligible studies (identified using MEDLINE) were those reporting response and/or survival data for patients with well-differentiated non-pNETs receiving systemic chemotherapy. The primary end-point was overall-response (OR) rate; secondary end points were progression-free survival (PFS), overall survival (OS), disease stabilization (DS) and disease-control (DC) rates. RESULTS: Of 6434 studies screened, 20 were eligible: one randomised phase III trial, 2 randomised phase II studies, 10 single-arm phase II trials and 7 retrospective analyses including a total of 264 patients (median of 11 patients per study, range 6-49); and employing multiple chemotherapy schedules. The mean "median PFS" and "median OS" were 16.9 months (95%-confidence interval (CI) 3.8-30.04) and 32.2 months (95%-CI 10.4-54.2), respectively. The non-weighted mean OR, DS and DC rates were 11.5% (95%-CI 5.8-17.2), 56.5% (95%-CI 38.1-74.9) and 70.7% (95%-CI 54.9-86.5), respectively. In studies including both pNETs and non-pNET patients, meta analysis showed a lower OR-rate in the non-pNET patients when compared to pNETs [odds ratio (OR) 0.35 (95% CI 0.18-0.66)]; however significance was lost when high-risk bias studies were excluded in a sensitivity analysis [OR 0.45 (95% CI 0.19-1.07); p-value 0.07]. CONCLUSION: Studies were of evidence level-C with heterogeneous populations and treatments; and small patient numbers. Well designed, prospective studies are needed to adequately evaluate the role of chemotherapy in this setting. PMID- 26855377 TI - STaQTool: Spot tracking and quantification tool for monitoring splicing of single pre-mRNA molecules in living cells. AB - The vast majority of human protein-coding genes contain up to 90% of non-coding sequence in the form of introns that must be removed from the primary transcripts or pre-mRNAs. Diverse forms of mRNAs encoded from a single gene are created by the differential use of splice sites and alternative splicing is rapidly evolving. Although the kinetic properties of splicing are thought to be critical for proofreading and regulatory mechanisms, tools for making direct experimental measurements of splicing rates are still limited. We recently developed a strategy that permits real-time imaging of fluorescent-labelled introns in single pre-mRNA molecules. Here we describe the software tool that we created for automatic tracking and quantification of intronic fluorescence at the site of transcription in live human cells. PMID- 26855378 TI - First molecular detection of Mycobacterium bovis in environmental samples from a French region with endemic bovine tuberculosis. AB - AIMS: The aim of the study was to determine the prevalence of Mycobacterium bovis (the causative agent of bovine tuberculosis, bTB) in environmental matrices within a French region (Cote d'Or) affected by this zoonotic disease. METHODS AND RESULTS: We report here the development and the use of molecular detection assays based on qPCR (double fluorescent dye-labelled probe) to monitor the occurrence of Mycobacterium tuberculosis complex (MTBC) or Myco. bovis in environmental samples collected in pastures where infected cattle and wildlife had been reported. Three qPCR assays targeting members of the MTBC (IS1561' and Rv3866 loci) or Myco. bovis (RD4 locus) were developed or refined from existing assays. These tools were validated using Myco. bovis spiked soil, water and faeces samples. Environmental samples were detected positive for the presence of MTBC strains and Myco. bovis in the environment of bTB-infected farms in the Cote d'Or region. CONCLUSIONS: The development of molecular assays permitted testing of several types of environmental samples including spring water, sediment samples and soils from badger setts entrance located in the vicinity of these farms, which were repeatedly contaminated with Myco. bovis (up to 8.7 * 10(3) gene copies per gram of badger sett soil). For the first time, direct spoligotyping of soil DNA enabled identification of Myco. bovis genotypes from environmental matrices. SIGNIFICANCE AND IMPACT OF THE STUDY: All together, these results suggest that Myco. bovis occurs at low levels in environmental matrices in Cote d'Or within the bTB-infected area. Drinking contaminated water or inhaling contaminated bioaerosols might explain cattle infection in some cases. PMID- 26855379 TI - Identification and structural elucidation of three new tadalafil analogues found in a dietary supplement. AB - Compounds elucidated as new tadalafil analogues were found to be adulterated in a dietary supplement and detected during routine analysis by HPLC with photodiode array detection. The UV spectra of these compounds were found to be almost identical to that of tadalafil. The unknown compounds were isolated by preparative HPLC and elucidated by quadrupole-time-of-flight MS and NMR spectroscopy. Two compounds were identified as cyclopentyltadalafil and trans cyclopentyltadalafil, from the substitution of the tadalafil N-methyl group with a cyclopentyl group. Another analogue was a dimeric form of tadalafil with an N cyclopentyl group. This represents the first report of the elucidation of compounds used as adulterants in a dietary supplement. PMID- 26855380 TI - Characterization of three main degradation products from novel oral anticoagulant rivaroxaban under stress conditions by UPLC-Q-TOF-MS/MS. AB - Drugs of long-term use may cause the accumulation of chemical compounds in human body. Therefore, the evaluation and structure characterization of synthesis and degradation impurities is substantial to guarantee drug safety and successful pharmaceutical therapy. The present work evaluated the anticoagulant rivaroxabana (RIV) under stress conditions in order to elucidate the chemical structure of major degradation products (DPs) formed after drug exposition to acid and alkaline hydrolysis, and UVC radiation. Analyses were performed in UPLC coupled to quadrupole time-of-flight MS. ESI was applied in positive mode, and C18 Agilent((r)) column (2.1*50 mm, 1.8 MUm) used for separation of compounds. RIV molecular ion [M+H](+) (m/z 436.07) was fragmented under 20 kV, best energetic condition to obtain clear and reproducible fragmentation pattern, assisting identification of RIV DPs. With support from UPLC separation and specific detection by MS/MS, three main degradation products (DP-1, DP-2, and DP-3) formed under stress conditions were successfully characterized. Presented study agrees with requirements for analytical assessment of impurities in pharmaceutical formulations, ensuring quality of pharmaceutical substances. PMID- 26855382 TI - Sniffing out the competition? Juvenile coral reef damselfishes use chemical cues to distinguish the presence of conspecific and heterospecific aggregations. AB - Aquatic animals commonly rely on chemical cues to provide information regarding their surroundings. They can respond either by being attracted to (potential mates, preferred habitats) or avoiding (predators, competitors) the source of the stimuli. Coral reef fishes use chemical cues to detect habitats, avoid predators and recognise conspecifics. However, the extent to which chemical cues are used to detect and respond to potential competitors, has received little attention. Here we test olfactory preferences for conspecifics and heterospecifics in newly settled juvenile coral reef fishes. Juveniles of 4 common coral-associated damselfish species: Dascyllus melanurus, Dascyllus reticulatus, Chrysiptera arnazae and Pomacentrus moluccensis, were subjected to olfactory choice tests. Three of the 4 species (excluding P. moluccensis) demonstrated preferences for waterborne conspecifics odours. All species exhibited an avoidance towards heterospecific odours; this aversion was consistently greatest towards P. moluccensis. A neutral response toward heterospecifics was only evident in two instances (1) between the two congeneric Dascyllus species, with D. melanurus toward D. reticulatus, and (2) with C. arnazae toward D. melanurus. While it is already known that the presence of conspecifics plays a vital role in settlement site selection, we show here that the presence of heterospecifics may also be key in determining the spatial distributions of juveniles across areas of coral reef. PMID- 26855383 TI - How heterogeneous is the involvement of ABC transporters against insecticides? AB - Understanding the molecular mechanisms underlying cellular defense against xenobiotic compounds is a main research issue in medical and veterinary entomology, as insecticide/acaricide resistance is a major threat in the control of arthropods. ABC transporters are recognized as a component of the detoxifying mechanism in arthropods. We investigated the possible involvement of ABC transporters in defense to the organophosphate insecticide temephos in the malarial vector Anopheles stephensi. We performed bioassays on larvae of An. stephensi, using insecticide alone and in combination with ABC-transporter inhibitors, to assess synergism between these compounds. Next, we investigated the expression profiles of six ABC transporter genes in larvae exposed to temephos. Surprisingly, neither bioassays nor gene expression analyses provided any evidence for a major role of ABC transporters in defense against temephos in An. stephensi. We thus decided to review existing literature to generate a record of other studies that failed to reveal a role for ABC transporters against particular insecticides/acaricides. A review of the scientific literature led to the recovery of 569 papers about ABC transporters; among these, 50 involved arthropods, and 10 reported negative results. Our study on An. stephensi and accompanying literature review highlight the heterogeneity that exists in ABC transporter involvement in defense/resistance mechanisms in arthropods. PMID- 26855384 TI - Studying of cellular interaction of hairpin-like peptide EcAMP1 from barnyard grass (Echinochloa crusgalli L.) seeds with plant pathogenic fungus Fusarium solani using microscopy techniques. AB - An interaction of recombinant hairpin-like cationic peptide EcAMP1 with conidia of plant pathogenic fungus Fusarium solani at the cellular level was studied by a combination of microscopic methods. EcAMP1 is from barnyard grass (Echinochloa crusgalli L.), and obtained by heterologous expression in Escherichia coli system. As a result, a direct relationship between hyphal growth inhibition and increasing active peptide concentration, time of incubation and fungal physiological condition has been determined. Dynamics of accumulation and redistribution of the peptide studied on fungal cellular cover and inside the conidia cells has been shown. The dynamics are dependent on time of coupling, as well as, a dissimilarity of EcAMP1 binding with cover of fungal conidia and its stepwise accumulation and diffuse localization in the cytoplasm. Correlation between structural disruption of fungal conidia and the presence of morphological changes has also been found. The correlation was found under the influence of peptide high concentrations at concentrations above 32 MUM. The results indicate the presence of a binding of EcAMP1 with the surface of fungal conidia, thus, demonstrating a main specificity for its antifungal action at the cellular level. These results, however, cannot exclude the existence of attendant EcAMP1 action based on its intracellular localization on some specific targets. SCANNING 38:591 598, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26855385 TI - Functional Results of Laparoscopic Pyeloplasty in Children: Single Institute Experience in Long Term. AB - OBJECTIVE: The aim of this study was to evaluate the long-term functional outcomes of laparoscopic pyeloplasty (LP) in children for consecutive cases of single institute. MATERIALS AND METHODS: Our laparoscopy database was investigated for children in terms of LP between June 2008 and April 2015. All the patients had ureteropelvic junction obstruction (UPJO) and LP was performed. Demographic data including age, gender, side of UPJO, operation time, estimated blood loss (EBL), hospital stay and complications according to Clavien classifications were recorded. Renal ultrasonography and diethylenetriamine penta acetate (DTPA) scintigraphies were respectively performed 3, 12 and 24 months after surgery. Statistical analyses were performed and p value was accepted as significant at <0.05. RESULT: Mean follow-up was 34 +/- 4.7 months. The mean age was 13 (6-72) months. A total of 153 (110 boys and 43 girls) LP patients enrolled. Of that, 93 (60.78%) LP were in left side and 60 (39.21%) were in right side. Three cases needed open conversation according to difficulties in anastomosis. Aberrant crossing vessel was observed in 12 (7.84%) patients. The mean operation time was 155 +/- 21 min and the mean EBL was 22 +/- 11.1 ml. The mean hospital stay was 3.4 days. Anastomotic leakage was the common complication (in 13 patients) that was successfully managed conservatively (Clavien 1). Eight patients experienced unsuccessful LP and underwent open pyeloplasty (Clavien 3b). The mean split renal function significantly increased in DTPA scintigraphy in follow-up. The overall success was 91%. CONCLUSIONS: The LP procedure can be an effective and safe surgical method for childhood UPJO, specifically in the experienced hands of pioneer centers. PMID- 26855386 TI - In-situ determination of field-scale NAPL mass transfer coefficients: Performance, simulation and analysis. AB - Better estimates of non-aqueous phase liquid (NAPL) mass, its persistence into the future, and the potential impact of source reduction are critical needs for determining the optimal path to clean up sites impacted by NAPLs. One impediment to constraining time estimates of source depletion is the uncertainty in the rate of mass transfer between NAPLs and groundwater. In this study, an innovative field test is demonstrated for the purpose of quantifying field-scale NAPL mass transfer coefficients (kl(N)) within a source zone of a fuel-contaminated site. Initial evaluation of the test concept using a numerical model revealed that the aqueous phase concentration response to the injection of clean groundwater within a source zone was a function of NAPL mass transfer. Under rate limited conditions, NAPL dissolution together with the injection flow rate and the radial distance to monitoring points directly controlled time of travel. Concentration responses observed in the field test were consistent with the hypothetical model results allowing field-scale NAPL mass transfer coefficients to be quantified. Site models for groundwater flow and solute transport were systematically calibrated and utilized for data analysis. Results show kl(N) for benzene varied from 0.022 to 0.60d(-1). Variability in results was attributed to a highly heterogeneous horizon consisting of layered media of varying physical properties. PMID- 26855387 TI - Utility of mammography for chronic kidney disease patients undergoing kidney transplant evaluation. AB - Transplant centers typically require screening mammography (MMG) for women >=40 during evaluation. American Cancer Society recommends starting annual MMG at 40, while USPSTF recommends biennial MMG at 50. We sought to determine the effect of age and other breast malignancy risk factors on screening MMG in the pre transplant renal failure population undergoing transplant evaluation. METHODS: We retrospectively examined women >=40 undergoing kidney transplant evaluation from 2006 to 2012 (n = 541). RESULTS: Patients aged 40.0-49.9 and >=50 had similar rates of breast biopsy and breast malignancy. African Americans underwent a higher rate of biopsies (OR 2.391, 95%CI 1.111-5.019, p = 0.026), with a lower rate of biopsy in those already on dialysis at presentation (OR 0.434, 95%CI 0.212-0.888, p = 0.022). Higher breast density (>50% fibroglandular tissue) increased both rate of biopsy (OR 2.876, 95%CI 1.377-6.010, p = 0.005) and malignancy (OR 5.061, 95%CI 1.012-25.315, p = 0.048). CONCLUSIONS: As we found no independent differences in biopsy or malignancy between age groups, it is reasonable for transplant centers to use the same evaluation MMG screening policy for all women >=40. However, as malignancy risk increased with higher breast density, a lower threshold for additional workup may be warranted in patients with dense breasts or an indeterminate lesion on MMG. PMID- 26855388 TI - Center the Patient in the Decision Process: A Tool to Inform the Consent and Share the Decision-Making in Patients With Rectal Cancer. PMID- 26855389 TI - Evaluation of the Rectal Cancer Patient Decision Aid: A Before and After Study. AB - BACKGROUND: In rectal cancer surgery, low anterior resection and abdominoperineal resection have equivocal impact on overall quality of life. A rectal cancer decision aid was developed to help patients weigh features of options and share their preference. OBJECTIVE: The aim of this study was to evaluate the effect of a patient decision aid for mid to low rectal cancer surgery on the patients' choice and decision-making process. DESIGN: A before-and-after study was conducted. Baseline data collection occurred after surgeon confirmation of eligibility at the first consultation. Patients used the patient decision aid at home (online and/or paper-based formats) and completed post questionnaires. SETTING: This study was conducted at an academic hospital referral center. PATIENTS: Adults who had rectal cancer at a maximum of 10 cm proximal to the anal verge and were amenable to surgical resection were considered. Those with preexisting stoma and those only receiving abdominoperineal resection for technical reasons were excluded from the study. INTERVENTION: Patient with rectal cancer were provided with a decision aid. MAIN OUTCOME MEASURES: The primary outcomes measured were decisional conflict, knowledge, and preference for a surgical option. RESULTS: Of 136 patients newly diagnosed with rectal cancer over 13 months, 44 (32.4%) were eligible, 36 (81.9%) of the eligible patients consented to participate, and 32 (88.9%) patients completed the study. The mean age of participants was 61.9 +/- 9.7 years and tumor location was on average 7.3 +/- 2.1 cm above the anal verge. Patients had poor baseline knowledge (52.5%), and their knowledge improved by 37.5% (p < 0.0001) after they used the patient decision aid. Decisional conflict was reduced by 24.2% (p = 0.0001). At baseline, no patients preferred a permanent stoma, and after decision aid exposure, 2 patients (7.1%) preferred permanent stoma. Over 96% of participants would recommend the patient decision aid to others. LIMITATIONS: This study was limited by the lack of control for potential confounders and potential response bias. CONCLUSIONS: The patient decision aid reduced decisional conflict and improved patient knowledge. Participants would recommend it to other patients with rectal cancer. PMID- 26855390 TI - Transanal Local Excision for Patients With Rectal Cancer: Can Radiation Compensate for What Is Perceived as a Nondefinitive Surgical Approach? AB - BACKGROUND: Total mesorectal excision has long been the standard of care for patients with rectal cancer. However, in select patients, local excision is an appropriate alternative option. The role of adjuvant radiation therapy in patients treated with local excision is controversial and evidence is lacking. OBJECTIVE: The purpose of this study was to report oncological outcomes of patients with rectal cancer treated with local excision and adjuvant radiation. DESIGN: This study was a retrospective chart review. SETTINGS: The study was conducted at the BC Cancer Agency, a tertiary referral hospital. PATIENTS: A total of 93 patients with node-negative rectal cancer treated with local excision and adjuvant radiotherapy between 2001 and 2010 were included in the study. MAIN OUTCOME MEASURES: Patient and tumor characteristics are reported. Five-year local control, progression-free survival, and overall survival were analyzed using Kaplan-Meier methods. RESULTS: Five-year overall survival, local control, and progression-free survival for patients treated with local excision and adjuvant radiotherapy were 78.5%, 86.1%, and 83.8%. In T1 disease, local control was 92.5%. LIMITATIONS: Referral bias, selection bias, lack of uniform surveillance, and retrospective analysis are the study limitations. CONCLUSIONS: Local excision with adjuvant radiotherapy provides a good level of local control in T1 disease and remains a good treatment option for patients who are either medically not suitable for a more radical surgical approach or who refuse this procedure. Local excision and radiotherapy should not be advocated in T2/T3 disease; however, it can provide a good alternative in those patients who are not fit enough for a more radical operation. PMID- 26855391 TI - Relative Value of Restaging MRI, CT, and FDG-PET Scan After Preoperative Chemoradiation for Rectal Cancer. AB - BACKGROUND: Management of rectal cancer has become multidisciplinary and is driven by the stage of the disease, with increased focus on restaging rectal cancer after neoadjuvant therapy. OBJECTIVE: The purpose of this study was to assess the relative impact of restaging after preoperative chemoradiation with FDG-PET scan, CT, and MRI in the management of patients with rectal cancer. DESIGN: This was a retrospective study from a single institution. SETTINGS: This study was conducted at a tertiary cancer center. PATIENTS: A total of 199 patients met the inclusion criteria: patients with rectal adenocarcinoma; staged with positron emission tomography, CT, and MRI; T2 to T4, N0 to N2, M0 to M1; treated with neoadjuvant chemoradiation 50.4 Gy and infusional 5-fluorouracil; and restaged 4 weeks after chemoradiation before surgery between 2003 and 2013. MAIN OUTCOME MEASURES: Comparisons of the tumor stage among different imaging modalities before and after neoadjuvant chemoradiation were performed. The impact of restaging on the management plan was assessed. RESULTS: The stage at presentation was T2, 8.04%; T3, 65.33%; T4, 26.63%; N0, 17.09%; N1, 47.74%; N2, 34.67%; M0, 81.91%; and M1, 18.09%. Changes in disease stage postneoadjuvant chemoradiation were observed in 99 patients (50%). The management plans of 29 patients (15%) were changed. The impact of each restaging modality on management for all of the patients was positron emission tomography, 11%; CT, 4%; and MRI, 4%. In patients with metastatic disease at primary staging, the relative impact of each restaging modality in changing management was positron emission tomography, 32%; CT, 18%; and MRI, 6%. LIMITATIONS: This study was limited by its single-center and retrospective design. Operations were performed 4 weeks after restaging. CONCLUSIONS: Changes in the extent of disease after long-course chemoradiotherapy result in changes of management in a significant percentage of patients. Positron emission tomography has the most significant impact in the change of management overall, and its use in restaging advanced rectal cancer should be further explored. PMID- 26855392 TI - Association Between Very Small Tumor Size and Increased Cancer-Specific Mortality in Node-Positive Colon Cancer. AB - BACKGROUND: Larger tumor size and lymph node involvement are traditionally associated with increased colon cancer-specific mortality. OBJECTIVE: We sought to determine whether patients with very small tumors associated with lymph node involvement are at paradoxically increased risk of colon cancer-specific mortality in comparison with those who have larger tumors and lymph node involvement. DESIGN: This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results database. SETTING: Geographic areas included in one of the 18 Surveillance, Epidemiology, and End Results registries were used. PATIENTS: We identified 99,594 patients with nonmetastatic colon adenocarcinoma treated with surgery between 1988 and 2001. MAIN OUTCOME MEASURES: The primary predictor variables were regional lymph node involvement and primary tumor size by longest dimension, grouped into the following predetermined strata: <5 mm, 5 to 19 mm, 20 to 39 mm, 40 to 59 mm, >= 60 mm. We used competing risks regression to determine differences in the risk of colon cancer-specific mortality between strata after controlling for T stage, tumor grade, age, year of diagnosis, race, and number of dissected lymph nodes. RESULTS: Median follow-up among censored patients was 12.9 years. We found a significant interaction between lymph node involvement and tumor size (p < 0.05). Among those with node-negative disease, colon cancer-specific mortality increased monotonically with tumor size. In contrast, among those with node-positive disease, patients with the smallest tumors (<5 mm) were at increased risk of 10-year colon cancer-specific mortality compared with those with tumors sized 5 to 19 mm, 20 to 39 mm, 40 to 59 mm, and >=60 mm (53.3% vs. 30.1%, 37.5%, 39.2%, and 39.7%; adjusted hazard ratios, 1.63 2.24; p < 0.05 in all cases). LIMITATIONS: The main limitations are the retrospective design and information available in the study database. CONCLUSION: In the setting of lymph node involvement, very small tumor size may predict for increased colon cancer-specific mortality compared with larger tumors. Smaller tumors associated with lymph node involvement may represent more aggressive malignancies with a distinct biology that merits further investigation. PMID- 26855393 TI - Effect of Diversion Ileostomy on the Occurrence and Consequences of Chemotherapy Induced Diarrhea. AB - BACKGROUND: The benefits of adjuvant chemotherapy in the treatment of colorectal cancer are well established. Chemotherapy-induced diarrhea is a common adverse effect of these regimens. The occurrence of chemotherapy-induced diarrhea not only directly affects patient health but may also compromise treatment efficacy because of consequent dosing alterations or discontinuation. OBJECTIVE: This study aimed to investigate the effect of diverting loop ileostomy during chemotherapy on the occurrence and consequences of chemotherapy-induced diarrhea. DESIGN: This was a retrospective evaluation of a prospective surgical database. SETTINGS: This was a single-institution retrospective study. PATIENTS: All patients receiving curative adjuvant chemotherapy after anterior resection for colorectal cancer at Auckland Hospital from 2002 to 2013 were retrospectively evaluated. MAIN OUTCOME MEASURES: Patient-, perioperative-, and chemotherapy related variables were collected. Chemotherapy-induced diarrhea occurrence was graded according to National Cancer Institute Common Terminology Criteria for Adverse Events. Logistic regression analysis was performed to identify independent predictors for chemotherapy-induced diarrhea occurrence, treatment modifications, and hospital admission. RESULTS: A total of 109 identified patients received 691 chemotherapy cycles; 84% of patients with a diverting ileostomy experienced chemotherapy-induced diarrhea compared with 47% in those who were not defunctioned (p < 0.01). On logistic regression analysis, the presence of a diverting ileostomy during chemotherapy was an independent predictor of chemotherapy-induced diarrhea grade 3 or higher (OR, 13.6 (95% CI: 1.2-150.9); p = 0.02), the need for a dosing reduction (OR, 4.0 (95% CI: 1.3 12.4); p = 0.02), and the need for any modification in the chemotherapy regimen (OR, 3.4 (95% CI: 1.2-9.6); p = 0.02). LIMITATIONS: This study is limited by its retrospective design, potentially limiting the accuracy of chemotherapy-induced diarrhea grade reporting. CONCLUSIONS: The presence of an ileostomy during adjuvant chemotherapy is a predictor of severe chemotherapy-induced diarrhea and the need for modifications in the chemotherapy regimen. This may have important consequences for long-term survival. Prospective investigation is needed to further assess the impact of diverting ileostomy on the delivery of chemotherapy and oncologic outcomes. PMID- 26855394 TI - Short-term Outcome of Robot-assisted and Open IPAA: An Observational Single center Study. AB - BACKGROUND: The potential advantages of robot-assisted laparoscopy are being increasingly investigated, although data on its efficacy in benign colorectal surgery are scarce. OBJECTIVE: We compared the early postoperative outcome in robot-assisted IPAA with open surgery procedures. DESIGN: This was an observational study based on prospectively collected data obtained from chart reviews. SETTING: The single-center data set covers patients operated on from January 13, 2004, to September 16, 2014, at a specialist center. PATIENTS: Patients with ulcerative colitis undergoing IPAA surgery were included. MAIN OUTCOME MEASURES: Study end points included the duration of operation, admission length, complications (Clavien-Dindo), reoperations, and readmissions. RESULTS: Eighty-one robot-assisted and 170 open IPAA procedures were performed. The duration of operation was significantly longer for robot-assisted laparoscopic procedures (mean difference, 154 minutes; CI, 140-170). During a mean follow-up of 102 days, no significant differences in the distribution of complications were found (Spearman p = 0.12; p = 0.07), and no postoperative deaths occurred in either group. Postoperative admission length was shorter following robot-assisted procedures (mean difference, -1.9; CI, -3.5 to -0.3), whereas 40% of patients were readmitted, compared with 26% of patients who had open surgery (OR, 1.9; CI, 1.1-3.4). Pouch failure occurred in 3 patients (1 following robot-assisted laparoscopy; 2 following open surgery). On multivariate regression analyses, robot-assisted laparoscopy was associated with a significantly longer duration of operation (mean difference, 159 minutes; CI, 144-174), and more readmissions for any cause (OR, 2; CI, 1.1-3.7). LIMITATIONS: This was a nonrandomized, single center observational study. CONCLUSION: In this implementation phase, robot assisted IPAA surgery offers acceptable short-term outcomes. The limitations of this observational study call for randomized controlled trials with long-term follow-up and exploration of functional results. PMID- 26855395 TI - Medically Treated Diverticular Abscess Associated With High Risk of Recurrence and Disease Complications. AB - BACKGROUND: The best management for diverticulitis with abscess formation remains unknown. OBJECTIVE: The purpose of this study was to determine the natural course and outcomes of patients with medically treated diverticular abscess. DESIGN: We conducted a retrospective review of all patients at our institution with diverticular abscess confirmed by CT from 2004 to 2014. SETTINGS: This study was conducted in a tertiary referral hospital. PATIENTS: A total of 1194 patients were treated for acute diverticulitis in 10 years; 210 patients with CT documented diverticular abscess were analyzed (140 men (66.7%) and 70 women (33.3%); median age 45 years; range, 23-84 years). MAIN OUTCOME MEASURES: Overall recurrence and disease complication rates, as well as the need for subsequent operation after initial successful nonsurgical management, were measured, along with analysis of the whole cohort and the subgroup of patients with percutaneous drainage for diverticular abscess. RESULTS: During the initial presentation, 25 patients failed nonoperative management and required an urgent operation. A total of 185 patients were initially successfully managed without surgery and were discharged from the hospital. Of these, recurrent diverticulitis developed in 112 (60.5%) after an average time interval of 5.3 months (range, 0.8-20.0 months); 47 patients (42%) experienced more than 1 episode. The modified Hinchey stage at time of recurrence (compared with index stay) increased in 51 patients (45.6%). Seventy one (63%) of 112 recurrences showed local disease complications (recurrent abscess, fistula, stricture, or peritonitis). Fistula formation (colovesicular/colovaginal/colocutaneous) and recurrent abscess were the 2 most frequent complications. Twenty nine (26%) of 112 recurrences required an urgent operation; overall, 66 (59%) of 112 patients eventually underwent surgery at our institution. The original abscess size in patients who later developed recurrences was significantly larger than in patients who did not develop recurrence (5.3 vs 3.2 cm; p < 0.001). Paradoxically, larger abscesses also had a higher chance of successful CT-guided drainage (average size, 6.5 cm; range, 1.1 14 cm), yet CT-guided drainage did not change the overall outcome. Of 65 (31.0%) of 210 patients with CT-guided drainage, 45 (73.8%) of 61 after initial success experienced a recurrence. Furthermore, local disease complications at the time of recurrence were noted in 32 of 61 patients (52.5% of all CT-guided drainage, 71.1% of post-CT-guided drainage recurrences), and 13 (29.2%) of 45 patients with recurrence after successful CT-guided drainage subsequently required an urgent operation. LIMITATIONS: The study was limited by its retrospective noncomparative design. CONCLUSIONS: Diverticular abscesses represent complicated diverticulitis and are associated with a high risk of recurrences and disease complications. Recurrences (contrary to other series) were often more severe than the index presentation. The successful CT-guided drainage of a diverticular abscess does not appear to lower the risks of future recurrence or complication rates and frequently is only a bridge to surgery. After initial successful nonoperative management, patients with diverticular abscess should be offered interval elective colectomy (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A216). PMID- 26855396 TI - Higher Mortality in Surgically Managed Diverticulitis is Associated with Asian Ethnicity and Right-Sided Disease. AB - BACKGROUND: Although right-sided diverticulitis is perceived to have a higher incidence among Asians and infrequently requires surgical management in comparison with sigmoid diverticulitis, it is unknown whether differences in outcomes are due to ethnic disparity or disease pathophysiology. OBJECTIVE: The aim of this study was to determine the surgical outcomes for Asian and non-Asian patients with diverticulitis who underwent colectomy. DESIGN: Patients identifiable by ethnicity in the Nationwide Inpatient Sample with diverticulitis and colectomy between 2004 and 2010 were included. Univariate comparisons were made between Asian and non-Asian patients by using t tests for continuous variables and chi tests for categorical variables. Propensity score matching analysis was performed to compare Asian patients with otherwise similar non-Asian patients. PATIENTS: Included were 58,142 non-Asian and 335 Asian patients with diverticulitis who underwent a colectomy. MAIN OUTCOME MEASURES: The primary outcomes were in-hospital mortality, hospital length of stay, and total costs. RESULTS: Asian patients were younger (56.1 vs. 59.2 years, p < 0.0001), were more likely to undergo a right colectomy (22.7% vs. 4.1%, p < 0.0001), and were more likely to have emergent/urgent surgery than the non-Asian patients (67.1% vs. 49.8%, p < 0.0001). Without controlling for patient/disease factors, there were statistically significant differences in mortality (non-Asian 2.2% vs. Asian 4.2%; p = 0.014), length of stay (non-Asian 8.9 vs. Asian 9.8 days; p = 0.0166), and costs (non-Asian $18,783 vs. Asian $21,901; p = 0.001). Propensity score matching comparing 333 non-Asian patients with 333 similar Asian patients showed that, whereas differences in cost and length of stay became insignificant, the difference in mortality remained statistically significant. LIMITATIONS: The ethnicity variable was not uniformly collected by all states within the Nationwide Inpatient Sample database. CONCLUSIONS: Among patients undergoing a colectomy for diverticulitis, a higher mortality was observed in Asian patients and right-sided disease. Future longitudinal studies comparing the natural history and outcomes of management between right- and left-sided diverticulitis are necessary to investigate whether a true ethnic disparity exists. PMID- 26855397 TI - Risk Factors for Postdischarge Venothromboembolism After Colorectal Resection. AB - BACKGROUND: Current guidelines recommend extended-duration thromboprophylaxis for all abdominal oncologic resections. However, other high-risk patients may benefit from extended thromboprophylaxis. OBJECTIVE: The purpose of this study was to identify risk factors for postdischarge venothromboembolism after colorectal procedures. DESIGN: This was a retrospective cohort study. DATA SOURCES: The New York Statewide Planning and Research Cooperative System database (2005-2013) was the data source for this study. STUDY SELECTION: Colon and rectal resections were evaluated. Cases with in-hospital mortality or length of stay >=30 days were excluded. MAIN OUTCOME MEASURES: Postdischarge venothromboembolism was defined at 30-days after the procedure requiring representation to the emergency department or hospital admission with a new diagnosis of venothromboembolism using International Classification of Diseases, Ninth Revision, codes. Factors associated with postdischarge venothromboembolism were then evaluated using a hierarchical bivariate analysis. A hierarchical mixed-effects model was created using a manual stepwise approach assessing variables meeting p < 0.1 on bivariate analysis. RESULTS: Among 128,163 patients, postdischarge venothromboembolism occurred in 0.7% (n = 789) of the population. Multiple factors were associated with postdischarge venothromboembolism on bivariate analysis. On multivariable analysis, benign conditions requiring operative intervention remained at high risk, with ulcerative colitis imparting an 93% increased odds when compared with other resections (OR, 1.93 (95% CI: 1.30-2.86); p = 0.001). Advanced malignancies (stages III and IV) were associated with increased postdischarge venothromboembolism risk, whereas stage I and II malignancies were not. The only protective factor was a laparoscopic procedure (OR, 0.80 (95% CI: 0.67-0.95); p = 0.010). There was no significant difference in procedure type after controlling for primary diagnosis. LIMITATIONS: This was a retrospective analysis of administrative data with inherent limitations. Only patients who presented with postdischarge venothromboembolism to a hospital within New York State were captured. CONCLUSIONS: This study identifies risk factors for postdischarge venothromboembolism and suggests that ulcerative colitis increases risk for postdischarge venothromboembolism whereas Crohn's disease does not. Ulcerative colitis postdischarge venothromboembolism rates exceeded even those of malignancy, suggesting that a future study is necessary to determine the efficacy of extended duration thromboprophylaxis in high-risk benign conditions, such as ulcerative colitis. PMID- 26855398 TI - Surgical Treatment of Anal Stenosis with Diamond Flap Anoplasty Performed in a Calibrated Fashion. AB - BACKGROUND: Regarding anoplasty for anal stenosis, it is not clear to what extent the final anal caliber should be targeted. OBJECTIVE: The aim of this study was to investigate the results of diamond-flap anoplasty performed in a calibrated manner for the treatment of severe anal stenosis due to a previous hemorrhoidectomy. DESIGN AND SETTING: Prospectively prepared standard forms were evaluated retrospectively. PATIENTS AND INTERVENTIONS: Anoplasty with unilateral or bilateral diamond flaps was performed for moderate or severe anal stenosis, targeting a final anal caliber of 25 to 26 mm. The demographic characteristics, causes of anal stenosis, number of previous surgeries, anal stenosis staging (Milsom and Mazier), anal calibers (millimeter), the Cleveland Clinic Incontinence Score, and the modified obstructed defecation syndrome Longo score were recorded on pre-prepared standard forms, as well as postoperative complications and the time of return to work. RESULTS: From January 2011 to July 2013, 18 patients (12 males, 67%) with a median age of 39 years (range, 27-70) were treated. All of the patients had a history of previous hemorrhoidectomy. The number of previous corrective interventions was 2.1 +/- 1.8 (range, 0-4), and 2 patients had a history of failed anoplasty. Five patients (28%) had moderate anal stenosis and 13 (72%) had severe anal stenosis. Preoperative, intraoperative, and 12-month postoperative anal calibration values were 9 +/- 3 mm (range, 5-15), 25 +/- 0.75 mm (range, 24-26), and 25 +/- 1 mm (range, 23-27) (p < 0.0001, for immediate postoperative and 12-month postoperative anal calibers compared with the intraoperative). Preoperative and 12-month postoperative Cleveland Clinic Incontinence Scores were 0.83 +/- 1.15 (range, 0-4) and 0.39 +/- 0.70 (range, 0 2) (p = 1.0). The clinical success rate was 88.9%. No severe postoperative complications were observed. LIMITATIONS: This study was limited because it was a single-armed, retrospective analysis of prospectively designed data. CONCLUSION: Diamond-flap anoplasty performed in a standardized and calibrated manner is a highly successful method for the treatment of anal stenosis caused by previous hemorrhoidectomy. PMID- 26855399 TI - Anastomotic Leaks After Restorative Resections for Rectal Cancer Compromise Cancer Outcomes and Survival. AB - BACKGROUND: Anastomotic leaks after restorative resections for rectal cancer may lead to worse long-term outcomes. OBJECTIVE: The purpose of this study was to evaluate the best current evidence assessing anastomotic leaks in rectal cancer resections with curative intent and their impact on survival and cancer recurrence. DATA SOURCES: A meta-analysis was performed using MEDLINE, EMBASE, and Cochrane search engines for relevant studies published between January 1982 and January 2015. STUDY SELECTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology was used to screen and select relevant studies for the review using key words "colorectal surgery; colorectal neoplasm; rectal neoplasm" and "anastomotic leak." INTERVENTION: Anastomotic leak groups were compared with nonanastomotic leak groups. MAIN OUTCOME MEASURES: ORs were calculated from binary data for local recurrence, distant recurrence, and cancer specific mortality. A random-effects model was then used to calculate pooled ORs with 95% CIs. RESULTS: Eleven studies with 13,655 patients met the inclusion criteria. This included 5 prospective cohort and 6 retrospective cohort studies. Median follow-up was 60 months. Higher cancer-specific mortality was noted in the leak group with an OR of 1.30 (95% CI, 1.04-1.62; p < 0.05). Local recurrences were more likely in rectal cancer resections complicated by anastomotic leaks (OR = 1.61 (95% CI, 1.25-2.09); p < 0.001). Distant recurrence was not more likely in the anastomotic leak group (OR = 1.07 (95% CI, 0.87-1.33); p = 0.52). LIMITATIONS: All 11 studies are level 3 evidence cohort studies. Additional sensitivity analyses were performed to minimize cross-study heterogeneity. CONCLUSIONS: Anastomotic leaks after restorative resections for rectal cancer adversely impact cancer-specific mortality and local recurrence. PMID- 26855400 TI - Robotic Anterior Resection for Sigmoid Colon Cancer Using Reduced Port Access. PMID- 26855401 TI - Transanal Total Mesorectal Excision: The Work is Progressing Well. PMID- 26855404 TI - Brown adipose tissue activation as measured by infrared thermography by mild anticipatory psychological stress in lean healthy females. AB - NEW FINDINGS: What is the central question of this study? Does psychological stress, which is known to promote cortisol secretion, simultaneously activate brown adipose tissue function in healthy adult females? What is the main finding and its importance? One explanation for the pronounced differences in brown adipose tissue function between individuals lies in their responsiveness to psychological stress and, as such, should be taken into account when examining its in vivo stimulation. Brown adipose tissue (BAT) has been implicated in the pathogenesis of obesity, type 2 diabetes and the metabolic syndrome and is a potential therapeutic target. Brown adipose tissue can have a significant impact on energy balance and glucose homeostasis through the action of uncoupling protein 1, dissipating chemical energy as heat following neuroendocrine stimulation. We hypothesized that psychological stress, which is known to promote cortisol secretion, would simultaneously activate BAT at thermoneutrality. Brown adipose tissue activity was measured using infrared thermography to determine changes in the temperature of the skin overlying supraclavicular BAT (TSCR ). A mild psychological stress was induced in five healthy, lean, female, Caucasian volunteers using a short mental arithmetic (MA) test. The TSCR was compared with a repeated assessment, in which the MA test was replaced with a period of relaxation. Although MA did not elicit an acute stress response, anticipation of MA testing led to an increase in salivary cortisol, indicative of an anticipatory stress response, that was associated with a trend towards higher absolute and relative TSCR . A positive correlation between TSCR and cortisol was found during the anticipatory phase, a relationship that was enhanced by increased cortisol linked to MA. Our findings suggest that subtle changes in the level of psychological stress can stimulate BAT, findings that may account for the high variability and inconsistency in reported BAT prevalence and activity measured by other modalities. Consistent assessment of this uniquely metabolic tissue is fundamental to the discovery of potential therapeutic strategies against metabolic disease. PMID- 26855405 TI - Hydrodynamics of a robotic fish tail: effects of the caudal peduncle, fin ray motions and the flow speed. AB - Recent advances in understanding fish locomotion with robotic devices have included the use of biomimetic flapping based and fin undulatory locomotion based robots, treating two locomotions separately from each other. However, in most fish species, patterns of active movements of fins occur in concert with the body undulatory deformation during swimming. In this paper, we describe a biomimetic robotic caudal fin programmed with individually actuated fin rays to mimic the fin motion of the Bluegill Sunfish (Lepomis macrochirus) and coupled with heave and pitch oscillatory motions adding to the robot to mimic the peduncle motion which is derived from the undulatory fish body. Multiple-axis force and digital particle image velocimetry (DPIV) experiments from both the vertical and horizontal planes behind the robotic model were conducted under different motion programs and flow speeds. We found that both mean thrust and lift could be altered by changing the phase difference (phi) from 0 degrees to 360 degrees between the robotic caudal peduncle and the fin ray motion (spanning from 3 mN to 124 mN). Notably, DPIV results demonstrated that the caudal fin generated multiple wake flow patterns in both the vertical and horizontal planes by varying phi. Vortex jet angle and thrust impulse also varied significantly both in these two planes. In addition, the vortex shedding position along the spanwise tail direction could be shifted around the mid-sagittal position between the upper and lower lobes by changing the phase difference. We hypothesize that the fish caudal fin may serve as a flexible vectoring propeller during swimming and may be critical for the high maneuverability of fish. PMID- 26855406 TI - DNA binding properties, histidine interaction and cytotoxicity studies of water soluble ruthenium(ii) terpyridine complexes. AB - In this study, two representatives of previously synthesized ruthenium(ii) terpyridine complexes, i.e., [Ru(Cl-tpy)(en)Cl][Cl] (1) and [Ru(Cl tpy)(dach)Cl][Cl] (2), were chosen and a detailed study of the kinetic parameters of their reactivity toward l-histidine (l-His), using the UV-Vis and (1)H NMR techniques, was developed. The inner molecular rearrangement from N3-coordinated l-His to the N1 bound isomer, observable in the NMR data, was corroborated by DFT calculations favoring N1 coordination by nearly 4 kcal mol(-1). These two ruthenium(ii) terpyridine complexes were investigated for their interactions with DNA employing UV-Vis spectroscopy, DNA viscosity measurements and fluorescence quenching measurements. The high binding constants obtained in the DNA binding studies (Kb = 10(4)-10(5) M(-1)) suggest a strong binding of the complexes to calf thymus (CT) DNA. Competitive studies with ethidium bromide (EB) showed that the complexes can displace DNA-bound EB, suggesting strong competition with EB (Ksv = 1.5-2.5 * 10(4) M(-1)). In fact, the results indicate that these complexes can bind to DNA covalently and non-covalently. In order to gain insight of the behavior of a neutral compound, besides the four previously synthesized cationic complexes [Ru(Cl-tpy)(en)Cl][Cl] (1), [Ru(Cl-tpy)(dach)Cl][Cl] (2), [Ru(Cl tpy)(bpy)Cl][Cl] (3) and [Ru(tpy)Cl3] (P2), a new complex, [Ru(Cl-tpy)(pic)Cl] (4), was used in the biological studies. Their cytotoxicity was investigated against three different tumor cell lines, i.e., A549 (human lung carcinoma cell line), HCT116 (human colon carcinoma cell line), and CT26 (mouse colon carcinoma cell line), by the MTT assay. Complexes 1 and 2 showed higher activity than complexes 3, 4 and P2 against all the selected cell lines. The results on in vitro anticancer activity confirmed that only compounds that hydrolyze the monodentate ligand at a reasonable rate show moderate activity, provided that the chelate ligand is a hydrogen bond donor. PMID- 26855407 TI - Assessment of renal function using intravoxel incoherent motion diffusion weighted imaging and dynamic contrast-enhanced MRI. AB - PURPOSE: To assess the correlation between each of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) metrics in renal parenchyma with renal function, in a cohort of patients with chronic liver disease. MATERIALS AND METHODS: Thirty patients with liver disease underwent abdominal MRI at 1.5T, including a coronal respiratory-triggered IVIM-DWI sequence and a coronal 3D FLASH DCE-MRI acquisition. Diffusion signals in the renal cortex and medulla were fitted to the IVIM model to estimate the diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF). The apparent diffusion coefficient (ADC) was calculated using all b-values. The glomerular filtration rate (GFR), cortical and medullary renal plasma flow (RPF), mean transit times (MTT) of vascular and tubular compartments and the whole kidney, were calculated from DCE-MRI data by fitting to a three-compartment model. The estimated GFR (eGFR) was calculated from serum creatinine measured 30 +/- 27 days of MRI. RESULTS: ADC, PF, and RPF were significantly higher in renal cortex vs. medulla (P < 10(-5) ). DCE-MRI GFR significantly correlated with, but underestimated, eGFR (Spearman's r/P = 0.49/0.01). IVIM-DWI parameters were not significantly correlated with eGFR. DCE MRI GFR correlated weakly with D (cortex, r/P = 0.3/0.03; medulla r/P = 0.27/0.05) and ADC (cortex r/P = 0.28/0.04; medulla r/P = 0.34/0.01). Weak correlations were observed for pooled cortical and medullar RPF with PF (r/P = 0.32/10(-3) ) and with ADC (r/P = 0.29/0.0025). Significant negative correlations were observed for vascular MTT with cortical D* (r/P = -0.38/0.004) and D**PF (r/P = -0.34/0.01). CONCLUSION: The weak correlations between renal IVIM and DCE MRI perfusion parameters imply that these functional measures could be complementary. J. Magn. Reson. Imaging 2016;44:317-326. PMID- 26855409 TI - Meningococcal Conjugate and Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccination Among HIV-infected Youth. AB - BACKGROUND: The meningococcal conjugate vaccine (MCV4) and the tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) were first recommended for adolescents in the US in 2005. The goal of our study was to determine MCV4 and Tdap vaccines coverage among perinatally and behaviorally HIV infected adolescents in 2006 and to compare coverage estimates in our study population to similarly aged healthy youth in 2006. METHODS: Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY) is a retrospective cohort study of HIV-infected youth in 22 HIV specialty clinics across the US. Among LEGACY participants >=11 years of age in 2006, we conducted a cross-sectional analysis to determine MCV4, Tdap and MCV4/Tdap vaccine coverage. We compared vaccine coverage among our study population to coverage among similarly aged youth in the 2006 National Immunization Survey for Teens (NIS-Teen Survey). Multivariable mixed effects logistic regression modeling was used to examine associations between MCV4/Tdap vaccination and mode of HIV transmission. RESULTS: MCV4 and Tdap coverage rates among 326 eligible participants were 31.6% and 28.8%, respectively. Among adolescents 13-17 years of age, MCV4 and Tdap coverage was significantly higher among HIV-infected youth than among youth in the 2006 NIS-Teen Survey (P <0.01). In multivariable analysis, perinatally HIV-infected youth were significantly more likely to have received MCV4/Tdap vaccination compared with their behaviorally infected counterparts (adjusted odds ratio: 5.1; 95% confidence interval: 2.0, 12.7). HIV infected youth with CD4 cell counts of 200-499 cells/MUL were more likely to have had MCV4/Tdap vaccination compared with those with CD4 counts >=500 cells/MUL (adjusted odds ratio: 2.2; 95% confidence interval: 1.2, 4.3). Participants with plasma HIV RNA viral loads of >400 copies/mL were significantly less likely to have received MCV4/Tdap vaccination (P < 0.05). CONCLUSIONS: MCV4 and Tdap coverage among HIV-infected youth was suboptimal but higher than for healthy adolescents in the 2006 NIS-Teen Survey. Perinatal HIV infection was associated with increased likelihood of vaccination. Specific measures are needed to improve vaccine coverage among adolescents in the US. PMID- 26855408 TI - Megaconial muscular dystrophy caused by mitochondrial membrane homeostasis defect, new insights from skeletal and heart muscle analyses. AB - Megaconial congenital muscular dystrophy is a disease caused by pathogenic mutations in the gene encoding choline kinase beta (CHKB). Microscopically, the disease is hallmarked by the presence of enlarged mitochondria at the periphery of skeletal muscle fibres leaving the centre devoid of mitochondria. Clinical characteristics are delayed motor development, intellectual disability and dilated cardiomyopathy in half of reported cases. This study describes a patient presenting with the cardinal clinical features, in whom a homozygous nonsense mutation (c.248_249insT; p.Arg84Profs*209) was identified in CHKB and who was treated by heart transplantation. Microscopic evaluation of skeletal and heart muscles typically showed enlarged mitochondria. Spectrophotometric evaluation in both tissues revealed a mild decrease of all OXPHOS complexes. Using BN-PAGE analysis followed by activity staining subcomplexes of complex V were detected in both tissues, indicating incomplete complex V assembly. Mitochondrial DNA content was not depleted in analysed tissues. This is the first report describing the microscopic and biochemical abnormalities in the heart from an affected patient. A likely hypothesis is that the biochemical findings are caused by an abnormal lipid profile in the inner mitochondrial membrane resulting from a defective choline kinase B activity. PMID- 26855410 TI - Temporal Changes in Pediatric Gastroenteritis after Rotavirus Vaccination in Quebec. AB - BACKGROUND: Rotavirus and norovirus are among the leading causes of pediatric gastroenteritis. We examined the relative burden of pediatric gastroenteritis by etiology and compared the clinical severity of rotavirus and norovirus cases after the November 2011 implementation of publicly funded rotavirus vaccination program in Quebec. METHODS: Prospective, active surveillance for acute gastroenteritis among children aged 8 weeks to less than 3 years of age was implemented at 3 hospitals. Participant demographics, clinical histories and stools were collected; stools were tested for rotavirus, norovirus and sapovirus. Risk and absolute differences of several clinical severity outcomes were compared by etiology with adjustment for patient age. RESULTS: From February 2012 to May 2014, 734 eligible active surveillance patients were recruited, and stools from 705 (96.0%) were tested and included in study analyses. Of these, 20.4% [95% confidence interval (CI): 16.5-24.3%] were rotavirus positive and 25.5% (95% CI: 21.3-29.8%) were norovirus positive, representing a difference of 5.1% (95% CI: 0.1-10.1%). When stratified by year, rotavirus and norovirus prevalence were similar from June 2012 to May 2013, but rotavirus prevalence was 21.4% (95% CI: 14.3-28.5%) lower than norovirus from June 2013 to May 2014. On average, rotavirus patients were more likely to be febrile, dehydrated, hospitalized and report more diarrheal episodes at the height of illness in comparison with norovirus patients of the same age. CONCLUSIONS: Norovirus infections were more prevalent than rotavirus infections among pediatric gastroenteritis cases hospitalized or seeking emergency care. Rotavirus cases were, on average, more clinically severe than norovirus cases among participants of the same age. PMID- 26855411 TI - PCSK9 inhibitors: an overview on a new promising lipid-lowering therapy. AB - Atherosclerosis is characterized by cholesterol deposition in the arterial intima, with subsequent plaque formation and arterial disease. Low-density lipoprotein cholesterol (LDL-C) plays the most important role in the atherogenesis process, which is the substrate of cardiovascular disease and is the leading cause of death worldwide. Several studies show that a strict control of risk factors, particularly the reduction of LDL-C levels, is a cornerstone in primary and secondary prevention of coronary heart disease. Statins are currently the most effective drugs for lowering LDL-C, but the discovery of proprotein convertase subtilisin kexin 9 (PCSK9) has opened up new therapeutic options in lipid management. PCSK9 reduces LDL-receptors' recycling resulting in a decrease of LDL-C receptors on the surface of hepatocytes and an increase of LDL-C levels in plasma. Obviously, inhibition of PCSK9 has been associated with an increase of LDL-C receptors with subsequent lowering of plasma levels of LDL-C. The clinical development of monoclonal antibodies against PCSK9 has been achieved through phase I and II studies, and nowadays there are many ongoing phase III trials with promising preliminary results. The aim of this review is to update the evidence for PCSK9 monoclonal antibodies, such as evolocumab, alirocumab and bococizumab, in LDL-C management and to discuss their therapeutic perspectives based on the most recent clinical studies, with attention to side-effects. PMID- 26855412 TI - Artificial biomembranes stabilized over spin coated hydrogel scaffolds. Crosslinking agent nature induces wrinkled or flat surfaces on the hydrogel. AB - Hydrogel films possess the ability of retain water and deliver it to a phospholipid bilayer mainly composed by DPPC (1,2-dipalmitoyl-sn-glycero-3 phosphocholine); moisture of the medium favors the stability of an artificial biomembrane when it is subjected to repetitive heating cycles. This hypothesis is valid when the hydrogel film, used as scaffold, present a flat surface morphology and a high ability for water releasing. On the other hand, when the sample presents a wrinkle topography (periodic undulations), free lateral molecular movement of the bilayer becomes lower, disfavoring the occurrence of clear phases/phase transitions according to applied temperature. Hydrogel films were prepared using HEMA (hydroxyethylmetacrylate), different crosslinking agents and initiators. This reaction mixture was spread over hydrophilic silicon wafers using spin coating technique. Resultant films were then exposed to UV light favoring polymeric chain crosslinking and interactions between hydrogel and substrate; this process is also known to generate tensile stress mismatch between different hydrogel strata, producing out-of-plane net force that generate ordered undulations or collapsed crystals at surface level. DPPC bilayers were then placed over hydrogel using Langmuir-Blodgett technique. Surface morphology was detected in order to clarify the behavior of these films. Obtained data corroborate DPPC membrane stability making possible to detect phases/phase transitions by ellipsometric methods and Atomic Force Microscopy due to their high hydration level. This system is intended to be used as biosensor through the insertion of transmembrane proteins or peptides that detect minimal variations of some analyte in the environment; artificial biomembrane stability and behavior is fundamental for this purpose. PMID- 26855413 TI - Synthesis of 6-chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives: Antidiabetic, antioxidant, beta-glucuronidase inhibiton and their molecular docking studies. AB - 6-Chloro-2-Aryl-1H-imidazo[4,5-b]pyridine derivatives 1-26 were synthesized and characterized by various spectroscopic techniques. All these derivatives were evaluated for their antiglycation, antioxidant and beta-glucuronidase potential followed their docking studies. In antiglycation assay, compound 2 (IC50=240.10+/ 2.50MUM) and 4 (IC50=240.30+/-2.90MUM) was found to be most active compound of this series, while compounds 3 (IC50=260.10+/-2.50MUM), 6 (IC50=290.60+/ 3.60MUM), 13 (IC50=288.20+/-3.00MUM) and 26 (IC50=292.10+/-3.20MUM) also showed better activities than the standard rutin (IC50=294.50+/-1.50MUM). In antioxidant assay, compound 1 (IC50=69.45+/-0.25MUM), 2 (IC50=58.10+/-2.50MUM), 3 (IC50=74.25+/-1.10MUM), and 4 (IC50=72.50+/-3.30MUM) showed good activities. In beta-glucuronidase activity, compounds 3 (IC50=29.25+/-0.50MUM), compound 1 (IC50=30.10+/-0.60MUM) and compound 4 (IC50=46.10+/-1.10MUM) showed a significant activity as compared to than standard D-Saccharic acid 1,4-lactonec (IC50=48.50+/ 1.25MUM) and their interaction with the enzyme was confirm by docking studies. PMID- 26855414 TI - Toxicity of natural insecticides on the larvae of wheat head armyworm, Dargida diffusa (Lepidoptera: Noctuidae). AB - The wheat head armyworm, Dargida (previously Faronta) diffusa (Walker) (Lepidoptera: Noctuidae), is widely distributed in North American grasslands and is most common on the Great Plains, where it is often a serious pest of corn and cereal crops. Six commercially available botanical or microbial insecticides used against D. diffusa were tested in the laboratory: Entrust((r)) WP (spinosad 80%), Mycotrol((r)) ESO (Beauveria bassiana GHA), Aza-Direct((r)) (azadirachtin), Met52((r)) EC (Metarhizium brunneum F52), Xpectro((r)) OD (Beauveria bassiana GHA+pyrethrins), and Xpulse((r)) OD (Beauveria bassiana GHA+azadirachtin). Concentrations of 0.1, 0.5, 1.0 and 2.0 fold the lowest labelled rates of formulated products were tested for all products, while for Entrust WP additional concentrations of 0.001 and 0.01 fold the label rates were also assessed. Survival rates were determined from larval mortality at 1-9 days post treatment application. We found that among the tested chemicals, Entrust((r)) (spinosad) was the most effective, causing 83-100% mortality (0-17% survival rate) at day 3 across all concentrations. The others, in order of efficacy from most to least, were Xpectro((r)) (B. bassiana GHA+pyrethrins), Xpulse((r))OD (B. bassiana GHA+azadirachtin), Aza-Direct((r)) (azadirachtin), Met52((r)) EC (M. brunneum F52), and Mycotrol((r)) ESO (B. bassiana GHA). These products and entomopathogenic fungi caused 70-100% mortality (0-30% survivability) from days 7 to 9. The tested products and entomopathogenic fungi can be used in management of D. diffusa. PMID- 26855415 TI - Partitioning and kinetics of methylmercury among organs in captive mink (Neovison vison): A stable isotope tracer study. AB - Despite the importance of methylmercury (MeHg) as a neurotoxin, we have relatively few good data on partitioning and kinetics of MeHg among organs, particularly across the blood-brain barrier, for mammals that consume large quantities of fish. The objective of this study was to determine the partition coefficients between blood and brain, liver and kidney and fur for MeHg under steady-state conditions and to measure the half-lives for MeHg in these organs. Captive mink (Neovison vison) were fed a diet enriched with two stable isotopes of Hg, Me(199)Hg and Me(201)Hg for a period of 60 days. After a period of 10 days the diet was changed to contain only Me(201)Hg so that, between days 10 and 60, we were able to measure both uptake and elimination rates from blood, brain, liver kidney and fur. Liver and kidney response was very rapid, closely following changes in blood concentrations but there was a small lag time between peak blood concentrations and peak brain concentrations. Half-lives for MeHg were 15.4, 10.2 and 13.4 days for brain, liver and kidney, respectively. There was no measurable conversion of the MeHg to inorganic Hg (IHg) in the brain over the 60 day period, unlike in liver and kidney. PMID- 26855416 TI - H3K9 acetylation change patterns in rats after exposure to traffic-related air pollution. AB - Traffic-related air pollution (TRAP) has been acknowledged as a potential risk factor for numerous respiratory disorders including lung cancer; however, the exact mechanisms involved are still unclear. Here we investigated the effects of TRAP exposure on the H3K9 acetylation in rats. The exposure was performed in both spring and autumn with identical study procedures. In each season, 48 healthy Wistar rats were exposed to different levels of TRAP for 4 h, 7 d, 14 d, and 28 d, respectively. H3K9 acetylation levels in both the peripheral blood mononuclear cells (PBMCs) and lung tissues were quantified. Multiple linear regression was applied to assess the influence of air pollutants on H3K9 acetylation levels. The levels of PM2.5, PM10, and NO2 in the tunnel and crossroad groups were significantly higher than in the control group. The H3K9 acetylation levels were not significantly different between spring and autumn. When spring and autumn data were analyzed together, no significant association between the TRAP and H3K9 acetylation was found in 4h exposure window. However, in the 7 d exposure window, PM2.5 and PM10 exposures were associated with changes in H3K9 acetylation ranging from 0.276 (0.053, 0.498) to 0.475 (0.103, 0.848) per 1 MUg/m(3) increase in the pollutant concentration. In addition, prolonged exposure of the rats in the tunnel showed that both PM2.5 and PM10 concentrations were positively associated with H3k9 acetylation in both PBMCs and lung tissues. The findings showed that 7 d and prolonged TRAP exposure could effectively increase the H3K9 acetylation level in both PBMCs and lung tissues of rats. PMID- 26855418 TI - The neutral sphingomyelinase-2 is involved in angiogenic signaling triggered by oxidized LDL. AB - Capillaries of the external part of the normal arterial wall constitute the vasa vasorum network. In atherosclerotic lesions, neovascularization occurs in areas of intimal hyperplasia where it may promote plaque expansion, and intraplaque hemorrhage. Oxidized LDL that are present in atherosclerotic areas activate various angiogenic signaling pathways, including reactive oxygen species and the sphingosine kinase/sphingosine-1-phosphate pathway. We aimed to investigate whether oxidized LDL-induced angiogenesis requires neutral sphingomyelinase-2 activation and the neutral sphingomyelinase-2/sphingosine kinase-1 pathway. The role of neutral sphingomyelinase-2 in angiogenic signaling was investigated in Human Microvascular Endothelial Cells (HMEC-1) forming capillary tube on Matrigel and in vivo in the Matrigel plug assay in C57BL/6 mice and in the chicken chorioallantoic membrane model. Low concentration of human oxidized LDL elicits HMEC-1 capillary tube formation and neutral sphingomyelinase-2 activation, which were blocked by neutral sphingomyelinase-2 inhibitors, GW4869 and specific siRNA. This angiogenic effect was mimicked by low concentration of C6-Ceramide and was inhibited by sphingosine kinase-1 inhibitors. Upstream of neutral sphingomyelinase-2, oxidized LDL-induced activation required LOX-1, reactive oxygen species generation by NADPH oxidase and p38-MAPK activation. Inhibition of sphingosine kinase-1 blocked the angiogenic response and triggered HMEC-1 apoptosis. Low concentration of oxidized LDL was angiogenic in vivo, both in the Matrigel plug assay in mice and in the chorioallantoic membrane model, and was blocked by GW4869. In conclusion, low oxLDL concentration triggers sprouting angiogenesis that involves ROS-induced activation of the neutral sphingomyelinase 2/sphingosine kinase-1 pathway, and is effectively inhibited by GW4869. PMID- 26855417 TI - The circadian gene Rev-erbalpha improves cellular bioenergetics and provides preconditioning for protection against oxidative stress. AB - Diurnal oscillations in the expression of antioxidant genes imply that protection against oxidative stress is circadian-gated. We hypothesized that stabilization of the core circadian gene Rev-erbalpha (Nr1d1) improves cellular bioenergetics and protects against nutrient deprivation and oxidative stress. Compared to WT, mouse lung fibroblasts (MLG) stably transfected with a degradation resistant Rev erbalpha (Ser(55/59) to Asp; hence referred to as SD) had 40% higher protein content, 1.5-fold higher mitochondrial area (confocal microscopy), doubled oxidative phosphorylation by high-resolution respirometry (Oroboros) and were resistant to glucose deprivation for 24h. This resulted from a 4-fold reduction in mitophagy (L3CB co-localized with MitoTracker Red) versus WT. Although PGC1alpha protein expression was comparable between SD and WT MLG cells, the role of mitochondrial biogenesis in explaining increased mitochondrial mass in SD cells was less clear. Embryonic fibroblasts (MEF) from C57Bl/6-SD transgenic mice, had a 9-fold induction of FoxO1 mRNA and increased mRNA of downstream antioxidant targets heme oxygenase-1 (HO-1), Mn superoxide dismutase and catalase (1.5, 2 fold and 2 fold respectively) versus WT. This allowed the SD cells to survive 1h incubation with 500 uM H2O2 as well as 24h of exposure to 95% O2 and remain attached whereas most WT cells did not. These observations establish a mechanistic link between the metabolic functions of Rev-erbalpha with mitochondrial homeostasis and protection against oxidative stress. PMID- 26855419 TI - Tousled kinase activator, gallic acid, promotes homologous recombinational repair and suppresses radiation cytotoxicity in salivary gland cells. AB - Accidental or medical radiation exposure of the salivary glands can gravely impact oral health. Previous studies have shown the importance of Tousled-like kinase 1 (TLK1) and its alternate start variant TLK1B in cell survival against genotoxic stresses. Through a high-throughput library screening of natural compounds, the phenolic phytochemical, gallic acid (GA), was identified as a modulator of TLK1/1B. This small molecule possesses anti-oxidant and free radical scavenging properties, but in this study, we report that in vitro it promotes survival of human salivary acinar cells, NS-SV-AC, through repair of ionizing radiation damage. Irradiated cells treated with GA show improved clonogenic survival compared to untreated controls. And, analyses of DNA repair kinetics by alkaline single-cell gel electrophoresis and gamma-H2AX foci immunofluorescence indicate rapid resolution of DNA breaks in drug-treated cells. Study of DR-GFP transgene repair indicates GA facilitates homologous recombinational repair to establish a functional GFP gene. In contrast, inactivation of TLK1 or its shRNA knockdown suppressed resolution of radiation-induced DNA tails in NS-SV-AC, and homology directed repair in DR-GFP cells. Consistent with our results in culture, animals treated with GA after exposure to fractionated radiation showed better preservation of salivary function compared to saline-treated animals. Our results suggest that GA-mediated transient modulation of TLK1 activity promotes DNA repair and suppresses radiation cytoxicity in salivary gland cells. PMID- 26855420 TI - Mitochondrial aldehyde dehydrogenase 2 protects gastric mucosa cells against DNA damage caused by oxidative stress. AB - Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a member of the aldehyde dehydrogenase superfamily and is involved with the metabolic processing of aldehydes. ALDH2 plays a cytoprotective role by removing aldehydes produced during normal metabolism. We examined the cytoprotective role of ALDH2 specifically in gastric mucosa cells. Overexpression of ALDH2 increased the viability of gastric mucosa cells treated with H2O2, while knockdown of ALDH2 had an opposite effect. Moreover, overexpression of ALDH2 protected gastric mucosa cells against oxidative stress-induced apoptosis as determined by flow cytometry, Hoechst 33342, and TUNEL assays. Consistently, ALDH2 knockdown had an opposite effect. Additionally, DNA damage was ameliorated in ALDH2-overexpressing gastric mucosa cells treated with H2O2. We further identified that this cytoprotective role of ALDH2 was mediated by metabolism of 4-hydroxynonenal (4-HNE). Consistently, 4-HNE mimicked the oxidative stress induced by H2O2 in gastric mucosa cells. Treatment with 4-HNE increased levels of DNA damage in ALDH2 knockdown GES-1 cells, while overexpression of ALDH2 decreased 4-HNE-induced DNA damage. These findings suggest that ALDH2 can protect gastric mucosa cells against DNA damage caused by oxidative stress by reducing levels of 4-HNE. PMID- 26855421 TI - Going retro: Oxidative stress biomarkers in modern redox biology. AB - The field of redox biology is inherently intertwined with oxidative stress biomarkers. Oxidative stress biomarkers have been utilized for many different objectives. Our analysis indicates that oxidative stress biomarkers have several salient applications: (1) diagnosing oxidative stress, (2) pinpointing likely redox components in a physiological or pathological process and (3) estimating the severity, progression and/or regression of a disease. On the contrary, oxidative stress biomarkers do not report on redox signaling. Alternative approaches to gain more mechanistic insights are: (1) measuring molecules that are integrated in pathways linking redox biochemistry with physiology, (2) using the exomarker approach and (3) exploiting -omics techniques. More sophisticated approaches and large trials are needed to establish oxidative stress biomarkers in the clinical setting. PMID- 26855422 TI - New strategies in sport nutrition to increase exercise performance. AB - Despite over 50 years of research, the field of sports nutrition continues to grow at a rapid rate. Whilst the traditional research focus was one that centred on strategies to maximise competition performance, emerging data in the last decade has demonstrated how both macronutrient and micronutrient availability can play a prominent role in regulating those cell signalling pathways that modulate skeletal muscle adaptations to endurance and resistance training. Nonetheless, in the context of exercise performance, it is clear that carbohydrate (but not fat) still remains king and that carefully chosen ergogenic aids (e.g. caffeine, creatine, sodium bicarbonate, beta-alanine, nitrates) can all promote performance in the correct exercise setting. In relation to exercise training, however, it is now thought that strategic periods of reduced carbohydrate and elevated dietary protein intake may enhance training adaptations whereas high carbohydrate availability and antioxidant supplementation may actually attenuate training adaptation. Emerging evidence also suggests that vitamin D may play a regulatory role in muscle regeneration and subsequent hypertrophy following damaging forms of exercise. Finally, novel compounds (albeit largely examined in rodent models) such as epicatechins, nicotinamide riboside, resveratrol, beta-hydroxy beta methylbutyrate, phosphatidic acid and ursolic acid may also promote or attenuate skeletal muscle adaptations to endurance and strength training. When taken together, it is clear that sports nutrition is very much at the heart of the Olympic motto, Citius, Altius, Fortius (faster, higher, stronger). PMID- 26855423 TI - Phenotypic evolution by distance in fluctuating environments: The contribution of dispersal, selection and random genetic drift. AB - Here we analyze how dispersal, genetic drift, and adaptation to the local environment affect the geographical differentiation of a quantitative character through natural selection using a spatial dynamic model for the evolution of the distribution of mean breeding values in space and time. The variation in optimal phenotype is described by local Ornstein-Uhlenbeck processes with a given spatial autocorrelation. Selection and drift are assumed to be governed by phenotypic variation within areas with a given mean breeding value and constant additive genetic variance. Between such neighboring areas there will be white noise variation in mean breeding values, while the variation at larger distances has a spatial structure and a spatial scale that we investigate. The model is analyzed by solving balance equations for the stationary distribution of mean breeding values. We also present scaling results for the spatial autocovariance function for mean breeding values as well as that for the covariance between mean breeding value and the optimal phenotype expressing local adaption. Our results show in particular how these spatial scales depend on population density. For large densities the spatial scale of fluctuations in mean breeding values have similarities with corresponding results in population dynamics, where the effect of migration on spatial scales may be large if the local strength of density regulation is small. In our evolutionary model strength of density regulation corresponds to strength of local selection so that weak local selection may produce large spatial scales of autocovariances. Genetic drift and stochastic migration are shown to act through the population size within a characteristic area with much smaller variation in optimal phenotypes than in the whole population. PMID- 26855424 TI - Possible light-induced superconductivity in K3C60 at high temperature. AB - The non-equilibrium control of emergent phenomena in solids is an important research frontier, encompassing effects such as the optical enhancement of superconductivity. Nonlinear excitation of certain phonons in bilayer copper oxides was recently shown to induce superconducting-like optical properties at temperatures far greater than the superconducting transition temperature, Tc (refs 4-6). This effect was accompanied by the disruption of competing charge density-wave correlations, which explained some but not all of the experimental results. Here we report a similar phenomenon in a very different compound, K3C60. By exciting metallic K3C60 with mid-infrared optical pulses, we induce a large increase in carrier mobility, accompanied by the opening of a gap in the optical conductivity. These same signatures are observed at equilibrium when cooling metallic K3C60 below Tc (20 kelvin). Although optical techniques alone cannot unequivocally identify non-equilibrium high-temperature superconductivity, we propose this as a possible explanation of our results. PMID- 26855425 TI - The peptidergic control circuit for sighing. AB - Sighs are long, deep breaths expressing sadness, relief or exhaustion. Sighs also occur spontaneously every few minutes to reinflate alveoli, and sighing increases under hypoxia, stress, and certain psychiatric conditions. Here we use molecular, genetic, and pharmacologic approaches to identify a peptidergic sigh control circuit in murine brain. Small neural subpopulations in a key breathing control centre, the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG), express bombesin-like neuropeptide genes neuromedin B (Nmb) or gastrin-releasing peptide (Grp). These project to the preBotzinger Complex (preBotC), the respiratory rhythm generator, which expresses NMB and GRP receptors in overlapping subsets of ~200 neurons. Introducing either neuropeptide into preBotC or onto preBotC slices, induced sighing or in vitro sigh activity, whereas elimination or inhibition of either receptor reduced basal sighing, and inhibition of both abolished it. Ablating receptor-expressing neurons eliminated basal and hypoxia-induced sighing, but left breathing otherwise intact initially. We propose that these overlapping peptidergic pathways comprise the core of a sigh control circuit that integrates physiological and perhaps emotional input to transform normal breaths into sighs. PMID- 26855427 TI - Non-destructive state detection for quantum logic spectroscopy of molecular ions. AB - Precision laser spectroscopy of cold and trapped molecular ions is a powerful tool in fundamental physics--used, for example, in determining fundamental constants, testing for their possible variation in the laboratory, and searching for a possible electric dipole moment of the electron. However, the absence of cycling transitions in molecules poses a challenge for direct laser cooling of the ions, and for controlling and detecting their quantum states. Previously used state-detection techniques based on photodissociation or chemical reactions are destructive and therefore inefficient, restricting the achievable resolution in laser spectroscopy. Here, we experimentally demonstrate non-destructive detection of the quantum state of a single trapped molecular ion through its strong Coulomb coupling to a well controlled, co-trapped atomic ion. An algorithm based on a state-dependent optical dipole force changes the internal state of the atom according to the internal state of the molecule. We show that individual quantum states in the molecular ion can be distinguished by the strength of their coupling to the optical dipole force. We also observe quantum jumps (induced by black-body radiation) between rotational states of a single molecular ion. Using the detuning dependence of the state-detection signal, we implement a variant of quantum logic spectroscopy of a molecular resonance. Our state-detection technique is relevant to a wide range of molecular ions, and could be applied to state-controlled quantum chemistry and to spectroscopic investigations of molecules that serve as probes for interstellar clouds. PMID- 26855428 TI - Entrapment of the flexor hallucis longus tendon following ankle arthrodesis. AB - Impingement following arthroscopic ankle arthrodesis has not been reported in the literature previously. We present a case report of a 68-year-old male 9 months following an uncomplicated arthroscopic ankle fusion presenting with persistent posteromedial ankle pain. Flexor hallucis longus (FHL) tendon impingement resulting from a prominent os trigonum was identified. This was successfully treated utilising hindfoot endoscopy with excision of the os trigonum and FHL release. PMID- 26855426 TI - Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer. AB - The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions. S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a mouse coronavirus S trimer ectodomain determined at 4.0 A resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins, implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains. PMID- 26855429 TI - Estrogenic Compounds Have Divergent Effects on Human Endothelial Progenitor Cell Migration according to Sex of the Donor. AB - BACKGROUND: Endothelial progenitor cells (EPCs) are key elements in vascular homeostasis. Their function is regulated by estrogens and estrogen receptors (ERs), but the effect of estrogenic compounds such as bisphenol A (BPA; an agonist of ER-beta and agonist and antagonist of ER-alpha) and (R,R)-5,11-diethyl 5,6,11,12-tetrahydro-2,8-chrysenediol (THC; an agonist of ER-alpha and antagonist of ER-beta) on human EPCs is unknown. We analyzed whether BPA and THC influence the migration of human EPCs, an essential process in endothelial regeneration, in both male and female EPCs. METHODS: EPCs isolated from healthy adult men and women were assayed for ER expression by Western blotting and chemotaxis assay. RESULTS: Male and female EPCs similarly expressed ERs and did not differ in basal migration. Interestingly, 17-beta-estradiol (10(-9) and 10(-10) M) significantly inhibited migration in female EPCs but not in males. Moreover, both 10(-5) M THC and 10(-8) M BPA blocked migration in female EPCs, allowing us to hypothesize that the effect is mediated by ER-alpha. CONCLUSIONS: Estrogenic compounds have a sex divergent effect which could help in understanding differences in the pathophysiology of endothelial function observed between men and women. PMID- 26855430 TI - Return of Voice for Ventilated Tracheostomy Patients in ICU: A Randomized Controlled Trial of Early-Targeted Intervention. AB - OBJECTIVES: A cuffed tracheostomy tube facilitates prolonged mechanical ventilation and weaning but usually leads to prolonged voicelessness, which can be one of the most negative experiences of hospitalization. No randomized trials have examined the effects of targeted early communication intervention for the restoration of voice in ventilated tracheostomy patients in the ICU. DESIGN: A prospective randomized clinical trial. SETTING: The trial was conducted in the ICU of an urban tertiary level hospital. PATIENTS: Thirty adult participants enrolled, with 15 randomly allocated to the intervention and control groups. INTERVENTIONS: The early intervention group received early cuff deflation and insertion of an in-line speaking valve during mechanical ventilation. The control group received standard cuff deflation and a speaking valve during self ventilation. A speech-language pathologist provided all treatments. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was time from tracheostomy insertion to phonation. Early intervention significantly hastened return to phonation (median difference = 11 d; hazard ratio = 3.66; 95% CI, 1.54-8.68) with no significant effect on duration of tracheostomy cannulation (hazard ratio = 1.40; 95% CI, 0.65-3.03), duration of mechanical ventilation in days from tracheostomy insertion (hazard ratio = 1.19; 95% CI, 0.58-2.51), length of stay in ICU (hazard ratio = 1.16; 95% CI, 0.54-2.52), or time to return to oral intake (hazard ratio = 2.35; 95% CI, 0.79-6.98). Adverse events were low and equal in both groups. There was no significant change in measures of quality of life. CONCLUSIONS: Focused early intervention for communication during mechanical ventilation allows the restoration of phonation significantly sooner than standard treatment, with no increase in complications in a small patient cohort. Although these results are favorable, further research is needed to determine whether the effects on any of the secondary outcomes are statistically significant and clinically important. PMID- 26855431 TI - Circulating Endothelial Progenitor Cells in Youth: Fitness, Physical Activity and Adiposity. AB - Circulating endothelial progenitor cells (EPCs) are early markers of cardiovascular impairment. The role of EPCs in youth remains unclear, and is complicated by differences in how cells are identified. This study (1) described EPCs in pre- and late-pubertal males and females, (2) examined their association with fitness, activity and adiposity, and (3) compared EPCs to published cell definitions. 94 participants completed 2 sessions. During the first session, aerobic fitness (Wpeak) and moderate-to-vigorous physical activity (MVPA) were assessed. During the second session, percent body fat (%BF) was determined by DXA, and a fasted blood sample was collected to measure EPCs by flow cytometry. EPCs were identified as CD31(+)CD34(bright)CD45(dim)CD133(+). Samples were reanalyzed and cell counts were compared to 8 previously published EPC definitions. EPCs were similar in pre- and late-pubertal males and females (p>0.05). Neither EPC concentrations nor proportions were correlated with Wpeak (rho=- 0.04 to-0.06), MVPA (rho=- 0.09 to - 0.07) or %BF (rho=0.20 to 0.14). Agreement between cell data analyzed according the different cell definitions ranged from Kappa=-0.06 to 0.82. Our findings suggest that EPCs were not associated with fitness, MVPA or adiposity in youth. The overall poor agreement across definitions may be indicative of distinct EPC subpopulations. PMID- 26855432 TI - The Effects of Forefoot Striking, Increasing Step Rate, and Forward Trunk Lean Running on Trunk and Lower Limb Kinematics and Comfort. AB - This study aimed to compare the immediate effects of 3 running technique modifications on the ankle, knee, hip and trunk kinematics and on the perceived comfort in healthy runners. The modifications were: forefoot striking pattern (FFOOT); increasing 10% of step rate (10% SR); and increasing forward trunk lean (FTL). 31 healthy runners participated. 3-dimensional lower limb and trunk kinematics were quantified while performing each condition on a treadmill. At initial contact, the FFOOT showed an increase in plantar flexion and knee external rotation, and reduction in knee flexion and adduction. During the stance phase, this condition showed greater peak knee external rotation and less mean and peak dorsiflexion and knee flexion. The 10% SR resulted in less hip flexion at initial contact. During the stance phase this technique showed less mean and peak knee flexion, peak reduction for dorsiflexion, knee abduction, hip flexion and hip adduction. At initial contact and during the stance phase, the FTL caused greater knee adduction and hip flexion. The usual running was the most comfortable technique. The techniques showed different lower limb kinematic modifications; which could potentially reduce knee injury risk. This knowledge is clinically relevant as it can be used to better prescribe techniques in prevention and rehabilitation programs. PMID- 26855433 TI - Validation of Instrumented Insoles for Measuring Height in Vertical Jump. PMID- 26855434 TI - No Acute Effect of Reduced-exertion High-intensity Interval Training (REHIT) on Insulin Sensitivity. PMID- 26855435 TI - Using Deception to Establish a Reproducible Improvement in 4-Km Cycling Time Trial Performance. AB - We investigated whether performance gains achieved with deception persisted after the deception was revealed, and whether pacing strategy changed. 14 trained cyclists completed 4 simulated 4-km time trials (TT) on a cycle ergometer comprising familiarization and baseline trials (BAS), followed by "unaware" (of deception, UAW) and "aware" (of deception, AW) trials on separate days. In the UAW trial, participants competed against an on-screen avatar set at 102% of their baseline trial mean power output (Pmean) believing it was set at 100% of BAS Pmean. 24 h prior to the AW trial, participants were informed of the deception in the UAW trial. 4 participants did not improve in the UAW trial compared to BAS. 10 participants improved time to completion (TTC) and Pmean in the UAW and AW trials compared to BAS (p<0.03) with no significant differences between UAW and AW (p=1.0). Pacing strategy (at 0.5-km intervals) and RPE responses were unchanged (p>0.05) for these participants. In summary, deception did not improve performance in all participants. However, participants whose time trial performance improved following deception could retain their performance gains once the deception was revealed, demonstrating a similar pacing strategy and RPE response. PMID- 26855436 TI - The first determination of DNA sequence of a specific gene. AB - How and when the first DNA sequence of a gene was determined? In 1977, F. Sanger came up with an innovative technology to sequence DNA by using chain terminators, and determined the entire DNA sequence of the 5375-base genome of bacteriophage phiX 174 (Sanger et al., 1977). While this Sanger's achievement has been recognized as the first DNA sequencing of genes, we had determined DNA sequence of a gene, albeit a partial sequence, 11 years before the Sanger's DNA sequence (Okada et al., 1966). PMID- 26855437 TI - Functional mixed effects spectral analysis. AB - In many experiments, time series data can be collected from multiple units and multiple time series segments can be collected from the same unit. This article introduces a mixed effects Cramer spectral representation which can be used to model the effects of design covariates on the second-order power spectrum while accounting for potential correlations among the time series segments collected from the same unit. The transfer function is composed of a deterministic component to account for the population-average effects and a random component to account for the unit-specific deviations. The resulting log-spectrum has a functional mixed effects representation where both the fixed effects and random effects are functions in the frequency domain. It is shown that, when the replicate-specific spectra are smooth, the log-periodograms converge to a functional mixed effects model. A data-driven iterative estimation procedure is offered for the periodic smoothing spline estimation of the fixed effects, penalized estimation of the functional covariance of the random effects, and unit specific random effects prediction via the best linear unbiased predictor. PMID- 26855438 TI - Tumour-adapted Reduction Mammoplasty - a New (Old) Breast Conserving Strategy: Review. AB - Today over 70 % of patients treated for primary breast carcinoma in certified breast centres are managed with breast conserving surgery. The classical semicircular incision directly above the tumour, though in many cases easily carried out and associated with good cosmetic results, does have limitations. Unsatisfactory aesthetic results often occur when tumour location is unfavourable or when there is unfavourable tumour size relative to breast size. Distortion of the nipple, changes to breast shape and retraction of skin overlying surgical defects can occur. Tumour-adapted reduction mammoplasty/mastopexy or the "modified B technique" offer excellent chances of combining the oncological demands of breast surgery with satisfactory symmetrical cosmetic results. This article reviews a traditional, old operative technique that has been re-embraced in various new forms. PMID- 26855439 TI - Ten Years of Patient Surveys in Accredited Breast Centers in North Rhine Westphalia. AB - Introduction: Patient surveys are an established tool for quality control in healthcare organizations. This report looks at the design and development of the annual patient surveys carried out among breast cancer patients treated in the Breast Centers of North Rhine-Westphalia and discusses selected findings from 10 consecutive years. Material and Methods: Since 2006 the Institute for Medical Sociology, Health Services Research and Rehabilitation Science (IMVR) of the University of Cologne has carried out an annual survey of breast cancer patients using the Cologne Patient Questionnaire for Breast Cancer. The patients included in the survey have been diagnosed with primary breast cancer and undergo surgery between February and July in one of the Breast Centers in North Rhine-Westphalia accredited by the medical association of Westphalia-Lippe. The questionnaire and the type of feedback given to the Breast Centers were comprehensively revised in 2014. Selected results collected over the survey period were analyzed descriptively. Results: The survey period of 10 years provides information on the actual medical care delivered in the Breast Centers based on the data obtained in this period from around 40 000 patients. Some areas showed positive developments over time. Conclusion: The approach used to survey patients, the Cologne Patient Questionnaire for Breast Cancer 2.0 and the benchmark-focused feedback provide an impetus for organizational learning in Breast Centers. The concept could also be used in other healthcare organizations to stimulate learning and improve healthcare services. PMID- 26855440 TI - Impact of Histopathological Factors, Patient History and Therapeutic Variables on Recurrence-free Survival after Ductal Carcinoma in Situ: 8-Year Follow-up and Questionnaire Survey. AB - Introduction: Ductal carcinoma in situ (DCIS) is a premalignant lesion of the glandular component of the breast and a precursor lesion of invasive breast cancer. In recent decades the incidence of DCIS has risen continuously, mainly because of more extensive screening and more advanced diagnostic procedures. There is an increasing need for evidence-based treatment guidelines which will protect patients as far as possible from recurrence or invasive cancer but also from overtreatment. This retrospective single-center clinical trial analyzed recurrence-free survival times, rates of invasive and non-invasive events, and the impact of patient history, histopathological variables and therapeutic factors on recurrence-free survival times. Material and Methods: A total of 200 patients who underwent surgery between 2000 and 2007 for pure DCIS were included in the study. As part of follow-up a questionnaire was sent to patients and their respective gynecologists. Results: In the follow-up period, 12.5 % (n = 25) of the 200 patients had recurrence (invasive or non-invasive event). Menopausal status, tumor grade and tumor size were significantly associated with recurrence. Low-grade DCIS was significantly more often hormone receptor-positive than high grade DCIS. Patients who had postoperative radiotherapy significantly more often also received endocrine drug treatment. There was a significant association between younger patient age and drug treatment. The study found that in the investigated cohort, premenopausal women had a significantly shorter recurrence free time compared to postmenopausal women. Conclusion: This paper summarizes the current literature on DCIS. There is a need for more prospective clinical trials to improve the prognosis of premenopausal women with large and hormone receptor positive DCIS. PMID- 26855441 TI - Femoral Placement of Totally Implantable Venous Access Ports in Patients with Bilateral Breast Cancer. AB - Purpose: Aim of this study was to determine the rate of complications following femoral placement of totally implantable venous access ports (f-TIVAP) in women with bilateral breast cancer, with a special focus on long-term function, deep vein thrombosis (DVT), and port infection. Methods: 73 patients with bilateral breast cancer treated between October 2000 and January 2013 with placement of an f-TIVAP using a transfemoral approach were retrospectively reviewed. All patients were followed up, and all complications of f-TIVAP were recorded. Results: The median age was 62.5 years (range: 35-86 years). Four patients received f-TIVAP under local anesthesia, and 69 underwent placement under general anesthesia. Mean follow-up was 33.7 months (SD 25.9; range: 0.2-93.5 months). Complications over the entire period of observation included infections in 21 %, DVT in 19 % and catheter occlusion in 12 %. Patients receiving chemotherapy who developed leukopenia were more likely to experience DVT at the access site (p = 0.037). There was a trend towards a higher infection rate when the device was used more often (p = 0.084). Conclusion: Although the rates of complications in the longer term, especially device infections and DVTs, appeared to be relatively high, TIVAP implantation using femoral vein access is recommended in patients with bilateral breast cancer not suitable for cephalic vein cut-down. PMID- 26855442 TI - Touch Imprint Cytology and Stereotactically-Guided Core Needle Biopsy of Suspicious Breast Lesions: 15-Year Follow-up. AB - Introduction: Stereotactically-guided core needle biopsies (CNB) of breast tumours allow histological examination of the tumour without surgery. Touch imprint cytology (TIC) of CNB promises to be useful in providing same-day diagnosis for counselling purposes and for planning future surgery. Having addressed the issue of accuracy of immediate microscopic evaluation of TIC, we wanted to re-examine the usefulness of this procedure in light of the present health care climate of cost containment by incorporating the surgical 15-year follow-up data and outcome. Patients and Methods: From January until December 1996 we performed TIC in core needle biopsies of 173 breast tumours in 169 patients, consisting of 122 malignant and 51 benign tumours. Histology of core needle biopsies was proven by surgical histology in all malignant and in 5 benign tumours. Surgical breast biopsy was not performed in 46 patients with 46 benign lesions, as the histological result from the core needle biopsy and the result of the TIC were in agreement with the suspected diagnosis from the complementary breast diagnostics. A 15-year follow-up of these patients followed in 2013 and follow-up data was collected from 40 women. Results: In the 15-year follow-up of the 40 benign lesions primarily confirmed using CNB and TIC, a diagnostic sensitivity, specificity, positive and negative predictive value and accuracy of 100 % was found. Conclusion: TIC and stereotactically guided CNB showed excellent long-term follow-up in patients with benign breast lesions. The use of TIC to complement CNB can therefore provide immediate cytological diagnosis of breast lesions. PMID- 26855443 TI - Distributional Language Learning: Mechanisms and Models of ategory Formation. AB - In the past 15 years, a substantial body of evidence has confirmed that a powerful distributional learning mechanism is present in infants, children, adults and (at least to some degree) in nonhuman animals as well. The present article briefly reviews this literature and then examines some of the fundamental questions that must be addressed for any distributional learning mechanism to operate effectively within the linguistic domain. In particular, how does a naive learner determine the number of categories that are present in a corpus of linguistic input and what distributional cues enable the learner to assign individual lexical items to those categories? Contrary to the hypothesis that distributional learning and category (or rule) learning are separate mechanisms, the present article argues that these two seemingly different processes-- acquiring specific structure from linguistic input and generalizing beyond that input to novel exemplars---actually represent a single mechanism. Evidence in support of this single-mechanism hypothesis comes from a series of artificial grammar-learning studies that not only demonstrate that adults can learn grammatical categories from distributional information alone, but that the specific patterning of distributional information among attested utterances in the learning corpus enables adults to generalize to novel utterances or to restrict generalization when unattested utterances are consistently absent from the learning corpus. Finally, a computational model of distributional learning that accounts for the presence or absence of generalization is reviewed and the implications of this model for linguistic-category learning are summarized. PMID- 26855444 TI - Orthotics Compared to Conventional Therapy and Other Non-Surgical Treatments for Plantar Fasciitis. AB - CLINICAL QUESTION: In adults with acute plantar fasciitis whose symptoms have not been relieved with the conventional regimen of NSAIDS, stretching and lifestyle modification, do the addition of orthotics (prefabricated or custom fitted) reduce pain and improve function compared with other non-surgical treatments (manipulative chiropractic, physical therapy and/or heel steroid injections)? ANSWER: Yes. Studies have shown that orthotics, both prefabricated and custom fitted, reduce pain and improve function in adults with acute plantar fasciitis with few risks or side effects. Used alone or in addition to conventional therapy (NSAIDs, stretching, lifestyle modification), orthotics are effective and well tolerated by patients for short-term pain relief and improved function. Prefabricated orthotics are less costly and provide similar relief to more expensive custom orthotics. Level of Evidence of the Answer: A Search Terms: Plantar fasciitis, heel pain, treatment, orthotics, Limits: Adult, human, English, Review, Randomized-Control Trials, Systematic Reviews, adults age 18 or more, publication dates 2004 to present. Date Search was Conducted: January 16, 2014; updated January 20, 2015 INCLUSION CRITERIA: Recent published systematic reviews, randomized controlled, meta-analyses; adults with confirmed acute or recent diagnosis of plantar fasciitis. EXCLUSION CRITERIA: Studies older than 10 years, children, adolescents less than 18 years of age, chronic or recalcitrant plantar fasciitis. PMID- 26855445 TI - Acknowledgement and the paradox of tragedy. AB - We offer a new answer to the paradox of tragedy. We explain part of the appeal of tragic art in terms of its acknowledgement of sad aspects of life and offer a tentative explanation of why acknowledgement is a source of pleasure. PMID- 26855446 TI - Effect of solid boundaries on swimming dynamics of microorganisms in a viscoelastic fluid. AB - We numerically study the effect of solid boundaries on the swimming behavior of a motile microorganism in viscoelastic media. Understanding the swimmer-wall hydrodynamic interactions is crucial to elucidate the adhesion of bacterial cells to nearby substrates which is precursor to the formation of the microbial biofilms. The microorganism is simulated using a squirmer model that captures the major swimming mechanisms of potential, extensile, and contractile types of swimmers, while neglecting the biological complexities. A Giesekus constitutive equation is utilized to describe both viscoelasticity and shear-thinning behavior of the background fluid. We found that the viscoelasticity strongly affects the near-wall motion of a squirmer by generating an opposing polymeric torque which impedes the rotation of the swimmer away from the wall. In particular, the time a neutral squirmer spends at the close proximity of the wall is shown to increase with polymer relaxation time and reaches a maximum at Weissenberg number of unity. The shear-thinning effect is found to weaken the solvent stress and therefore, increases the swimmer-wall contact time. For a puller swimmer, the polymer stretching mainly occurs around its lateral sides, leading to reduced elastic resistance against its locomotion. The neutral and puller swimmers eventually escape the wall attraction effect due to a releasing force generated by the Newtonian viscous stress. In contrast, the pusher is found to be perpetually trapped near the wall as a result of the formation of a highly stretched region behind its body. It is shown that the shear-thinning property of the fluid weakens the wall-trapping effect for the pusher squirmer. PMID- 26855447 TI - How Policy Makers Can Advance Cardiovascular Health. PMID- 26855448 TI - Robust Circadian Rhythm and Parathyroid Hormone-Induced Resetting during Hypertrophic Differentiation in ATDC5 Chondroprogenitor Cells. AB - Cartilage tissues possess intrinsic circadian oscillators, which influence chondrocyte function and chondrocyte specific gene expression. However, it is not fully understood how chondrogenesis influences the circadian clock, and vice versa. Thus, we established ATDC5 cells which were stably transfected with the Bmal1:luc reporter and revealed robust circadian rhythms in ATDC5 cells during differentiation. Moreover, the circadian clock in ATDC5 cells was strongly reset by PTH in a circadian time-dependent manner. This assay system is expected to be useful for investigating the role of the circadian clock in chondrogenic differentiation and the precise molecular mechanisms underlying PTH action on the chondrocyte circadian clock. PMID- 26855449 TI - CXCL14-Like Immunoreactivity Exists in Somatostatin-Containing Cells of Mouse Pancreas. AB - Immunohistochemical techniques were employed to investigate the distribution of the chemokine CXCL14, in the mouse pancreas. CXCL14-immunoreactive cells were detected in the peripheral region of the pancreatic islets and were immunoreactive for somatostatin, but not for glucagon, insulin, and pancreatic polypeptide. Immunoelectron microscopy indicated that the CXCL14-like peptide and somatostatin co-existed in the secretory granules. CXCL14, secreted from somatostatin-containing cells, may modulate insulin secretion in a paracrine fashion, and play a novel role in glucose homeostasis in addition to its well known chemotactic activities. PMID- 26855450 TI - Visualization of Kisspeptin Binding to Rat Hypothalamic Neurons. AB - The neuropeptide kisspeptin plays an important role in fertility and the onset of puberty, stimulating gonadotropin-releasing hormone (GnRH) neurons to activate the hypothalamic-pituitary-gonadal axis. Several studies have demonstrated a morphological interaction between kisspeptin- and GnRH-expressing neurons; however, few have addressed the interaction of kisspeptin with other neuronal subtypes. We recently showed that fibers immunoreactive for kisspeptin were densely distributed in the dorsal part of the arcuate nucleus. These fibers were found in close proximity to GnRH and tuberoinfundibular dopamine (TIDA) neurons. In the present study, using biotinylated kisspeptin, we established a visualization method for identifying kisspeptin binding sites on TIDA neurons. Biotinylated kisspeptin bound to the cell bodies of TIDA neurons and surrounding fibers, suggesting that TIDA neurons express sites of action for kisspeptin. Our assay also detected biotinylation signals from kisspeptin binding to GnRH fibers in the median eminence, but not to cell bodies of GnRH neurons in the medial preoptic area. Positive signals were completely eliminated by addition of excess non-labeled kisspeptin. This method enabled us to detect kisspeptin binding sites on specific neural structures and neuronal fibers. PMID- 26855452 TI - Insulin-Like Growth Factor II mRNA-Binding Protein 3 (IMP3) as a Useful Immunohistochemical Marker for the Diagnosis of Adenocarcinoma of Small Intestine. AB - The biological characteristics and roles of insulin-like growth factor II mRNA binding protein 3 protein (IMP3) expression in small-intestinal adenocarcinoma were investigated. The value of IMP3 immunostaining in the diagnosis of small intestinal epithelial lesions was also evaluated. Immunohistochemical expression of IMP3 in normal small-intestinal mucosa adjacent to adenoma and adenocarcinoma lesions, and inflamed duodenal and ileal mucosa was analyzed. Samples assessed were: duodenal ulcer (n=6), Crohn's disease (n=5), low-grade small-intestinal adenoma (n=10), high-grade small-intestinal adenoma (n=13), small-intestinal adenocarcinoma (n=23), lymph node metastases (LNM; n=7), and preoperative biopsies of small-intestinal adenocarcinoma (n=6). Immunohistochemical expression of Ki-67 and p53 was also analyzed in adenoma and adenocarcinoma samples. IMP3 was not expressed in normal epithelium, but weakly expressed in reparative epithelium. Meanwhile, increased IMP3 expression was associated with a higher degree of dysplasia in adenomas, higher T classification, LNM, Ki-67 positivity, histological differentiation, and lower 5-year disease-free survival, but not p53 expression in adenocarcinoma. IMP3 expression appears to be a late event in the small-intestinal carcinogenesis. Assessing the IMP3 staining pattern can be useful in the diagnosis of small-intestinal epithelial lesions when used in conjunction with other histological criteria. PMID- 26855451 TI - Maintenance of the Extracellular Matrix in Rat Anterior Pituitary Gland: Identification of Cells Expressing Tissue Inhibitors of Metalloproteinases. AB - The extracellular matrix (ECM) is important in creating cellular environments in tissues. Recent studies have demonstrated that ECM components are localized in anterior pituitary cells and affect cell activity. Thus, clarifying the mechanism responsible for ECM maintenance would improve understanding of gland function. Tissue inhibitors of metalloproteinases (TIMPs) are endogenous inhibitors of matrix metalloproteinases and participate in ECM degradation. In this study, we investigated whether cells expressing TIMPs are present in rat anterior pituitary gland. Reverse transcription polymerase chain reaction was used to analyze expression of the TIMP family (TIMP1-4), and cells producing TIMPs in the gland were identified by using in situ hybridization. Expression of TIMP1, TIMP2, and TIMP3 mRNAs was detected, and the TIMP-expressing cells were located in the gland. The TIMP-expressing cells were also investigated by means of double staining with in situ hybridization and immunohistochemical techniques. Double staining revealed that TIMP1 mRNA was expressed in folliculostellate cells. TIMP2 mRNA was detected in folliculostellate cells, prolactin cells, and thyroid stimulating hormone cells. TIMP3 mRNA was identified in endothelial cells, pericytes, novel desmin-immunopositive perivascular cells, and folliculostellate cells. These findings indicate that TIMP1-, TIMP2-, and TIMP3-expressing cells are present in rat anterior pituitary gland and that they are involved in maintaining ECM components. PMID- 26855453 TI - Transplantation of Neuro2a Cells into the Developing Postnatal Mouse Eye. AB - The present study aimed to investigate the influence of the host retinal microenvironment on cell migration and differentiation using Neuro2a (N2a) cells transduced with green fluorescent protein. N2a cells were transplanted into the vitreous cavities of developing mouse eyes (C57BL/6) on postnatal days 1, 5, and 10 (P1, 5, and 10). To analyze the effects of the host microenvironment on neural differentiation of N2a cells in vitro, cells were treated with a conditioned medium (CM) collected from retinal cells cultured at each developmental stage. We observed that numerous cells transplanted into P5 mice eyes migrated into all layers of the host retina, and the presence of processes indicated morphological differentiation. Some transplanted N2a cells expressed several neural markers. However, cells transplanted into the P1 and 10 mice eyes only proliferated within the vitreous cavity. Neurite length increased in N2a cells treated with CM collected from the cultured retinal cells from P5 and 10 mice, while western blotting revealed that the levels of proteins related to neural differentiation were not significantly altered in N2a cells treated with CM. We show that the migration and differentiation capacities of transplanted cells were differentially influenced by the microenvironment of the retinal postnatal ontogeny. PMID- 26855454 TI - Establishment risk of the commercially imported bumblebee Bombus terrestris dalmatinus-can they survive UK winters? AB - Bumblebees are regularly exported to countries outside their native range for the purposes of commercial pollination. In contrast to the tight regulations imposed on biological control introductions, the movement of bumblebees has largely been without risk assessment. This study represents the first formal assessment of establishment risk for Bombus terrestris dalmatinus in the UK. The ability of workers to survive winter conditions is seen as the primary barrier to establishment, given the year-round colony activity of this sub-species. We use standardised cold tolerance indices as outlined by the EU policy support action 'REBECA' as well as assessing rapid cold hardening (RCH) ability. Cold tolerance was comparable to that of the UK-native Bombus terrestris audax, including a strong RCH response. Results suggest that B. t. dalmatinus could survive mild UK winters in southern areas and potentially displace B. t. audax. The implications of ongoing climate change on establishment risks are discussed. PMID- 26855456 TI - Complex systems approach to scientific publication and peer-review system: development of an agent-based model calibrated with empirical journal data. AB - Scientific peer-review and publication systems incur a huge burden in terms of costs and time. Innovative alternatives have been proposed to improve the systems, but assessing their impact in experimental studies is not feasible at a systemic level. We developed an agent-based model by adopting a unified view of peer review and publication systems and calibrating it with empirical journal data in the biomedical and life sciences. We modeled researchers, research manuscripts and scientific journals as agents. Researchers were characterized by their scientific level and resources, manuscripts by their scientific value, and journals by their reputation and acceptance or rejection thresholds. These state variables were used in submodels for various processes such as production of articles, submissions to target journals, in-house and external peer review, and resubmissions. We collected data for a sample of biomedical and life sciences journals regarding acceptance rates, resubmission patterns and total number of published articles. We adjusted submodel parameters so that the agent-based model outputs fit these empirical data. We simulated 105 journals, 25,000 researchers and 410,000 manuscripts over 10 years. A mean of 33,600 articles were published per year; 19 % of submitted manuscripts remained unpublished. The mean acceptance rate was 21 % after external peer review and rejection rate 32 % after in-house review; 15 % publications resulted from the first submission, 47 % the second submission and 20 % the third submission. All decisions in the model were mainly driven by the scientific value, whereas journal targeting and persistence in resubmission defined whether a manuscript would be published or abandoned after one or many rejections. This agent-based model may help in better understanding the determinants of the scientific publication and peer-review systems. It may also help in assessing and identifying the most promising alternative systems of peer review. PMID- 26855457 TI - Effects of reading picture books on kindergartners' mathematics performance. AB - This article describes a field experiment with a pretest-posttest control group design which investigated the potential of reading picture books to children for supporting their mathematical understanding. The study involved 384 children from 18 kindergarten classes in 18 schools in the Netherlands. During three months, the children in the nine experimental classes were read picture books. Data analysis revealed that, when controlled for relevant covariates, the picture book reading programme had a positive effect (d = .13) on kindergartners' mathematics performance as measured by a project test containing items on number, measurement and geometry. Compared to the increase from pretest to posttest in the control group, the increase in the experimental group was 22% larger. No significant differential intervention effects were found between subgroups based on kindergarten year, age, home language, socio-economic status and mathematics and language ability, but a significant intervention effect was found for girls and not for boys. PMID- 26855455 TI - Chemical and biological mechanisms of phytochemical activation of Nrf2 and importance in disease prevention. AB - Plants are an incredibly rich source of compounds that activate the Nrf2 transcription factor, leading to upregulation of a battery of cytoprotective genes. This perspective surveys established and proposed molecular mechanisms of Nrf2 activation by phytochemicals with a special emphasis on a common chemical property of Nrf2 activators: the ability as "soft" electrophiles to modify cellular thiols, either directly or as oxidized biotransformants. In addition, the role of reactive oxygen/nitrogen species as secondary messengers in Nrf2 activation is discussed. While the uniquely reactive C151 of Keap1, an Nrf2 repressor protein, is highlighted as a key target of cytoprotective phytochemicals, also reviewed are other stress-responsive proteins, including kinases, which play non-redundant roles in the activation of Nrf2 by plant derived agents. Finally, the perspective presents two key factors accounting for the enhanced therapeutic windows of effective phytochemical activators of the Keap1-Nrf2 axis: enhanced selectivity toward sensor cysteines and reversibility of addition to thiolate molecules. PMID- 26855458 TI - Always Approach the Bright Side of Life: A General Positivity Training Reduces Stress Reactions in Vulnerable Individuals. AB - Emotional disorders are characterized by cognitive biases towards negative stimuli, and a lack of biases towards positive ones. Therefore, we developed a cognitive bias modification training, modifying approach-avoidance tendencies to diverse emotional pictures. In Study 1, a negative training (pull negative, push positive pictures) was compared to a positive training (vice versa) in 141 students. The pre-existing positivity bias remained after positive training, but reversed into a negativity bias after negative training. This effect transferred to an attentional bias. The training affected neither mood nor emotional vulnerability to stress. In Study 2, we investigated the effects of the positive training in 102 dysphoric and non-dysphoric students, all in a sad mood state. Compared to placebo training, the positive training strengthened a positivity bias, and it reduced emotional vulnerability in dysphoric students. This suggests potential therapeutic value of the training, but further studies are needed. PMID- 26855459 TI - False discovery rate regression: an application to neural synchrony detection in primary visual cortex. AB - Many approaches for multiple testing begin with the assumption that all tests in a given study should be combined into a global false-discovery-rate analysis. But this may be inappropriate for many of today's large-scale screening problems, where auxiliary information about each test is often available, and where a combined analysis can lead to poorly calibrated error rates within different subsets of the experiment. To address this issue, we introduce an approach called false-discovery-rate regression that directly uses this auxiliary information to inform the outcome of each test. The method can be motivated by a two-groups model in which covariates are allowed to influence the local false discovery rate, or equivalently, the posterior probability that a given observation is a signal. This poses many subtle issues at the interface between inference and computation, and we investigate several variations of the overall approach. Simulation evidence suggests that: (1) when covariate effects are present, FDR regression improves power for a fixed false-discovery rate; and (2) when covariate effects are absent, the method is robust, in the sense that it does not lead to inflated error rates. We apply the method to neural recordings from primary visual cortex. The goal is to detect pairs of neurons that exhibit fine time-scale interactions, in the sense that they fire together more often than expected due to chance. Our method detects roughly 50% more synchronous pairs versus a standard FDR-controlling analysis. The companion R package FDRreg implements all methods described in the paper. PMID- 26855460 TI - Comment. PMID- 26855461 TI - Formant measurement in children's speech based on spectral filtering. AB - Children's speech presents a challenging problem for formant frequency measurement. In part, this is because high fundamental frequencies, typical of a children's speech production, generate widely spaced harmonic components that may undersample the spectral shape of the vocal tract transfer function. In addition, there is often a weakening of upper harmonic energy and a noise component due to glottal turbulence. The purpose of this study was to develop a formant measurement technique based on cepstral analysis that does not require modification of the cepstrum itself or transformation back to the spectral domain. Instead, a narrow-band spectrum is low-pass filtered with a cutoff point (i.e., cutoff "quefrency" in the terminology of cepstral analysis) to preserve only the spectral envelope. To test the method, speech representative of a 2-3 year-old child was simulated with an airway modulation model of speech production. The model, which includes physiologically-scaled vocal folds and vocal tract, generates sound output analogous to a microphone signal. The vocal tract resonance frequencies can be calculated independently of the output signal and thus provide test cases that allow for assessing the accuracy of the formant tracking algorithm. When applied to the simulated child-like speech, the spectral filtering approach was shown to provide a clear spectrographic representation of formant change over the time course of the signal, and facilitates tracking formant frequencies for further analysis. PMID- 26855462 TI - Bright and ultra-fast scintillation from a semiconductor? AB - Semiconductor scintillators are worth studying because they include both the highest luminosities and shortest decay times of all known scintillators. Moreover, many semiconductors have the heaviest stable elements (Tl, Hg, Pb, Bi) as a major constituent and a high ion pair yield that is proportional to the energy deposited. We review the scintillation properties of semiconductors activated by native defects, isoelectronic impurities, donors and acceptors with special emphasis on those that have exceptionally high luminosities (e.g. ZnO:Zn, ZnS:Ag,Cl, CdS:Ag,Cl) and those that have ultra-fast decay times (e.g. ZnO:Ga; CdS:In). We discuss underlying mechanisms that are consistent with these properties and the possibilities for achieving (1) 200,000 photons/MeV and 1% fwhm energy resolution for 662 keV gamma rays, (2) ultra-fast (ns) decay times and coincident resolving times of 30 ps fwhm for time-of-flight positron emission tomography, and (3) both a high luminosity and an ultra-fast decay time from the same scintillator at cryogenic temperatures. PMID- 26855463 TI - Fear and Anger in Great Britain: Blame Assignment and Emotional Reactions to the Financial Crisis. AB - While we know that emotional reactions are important influences on political behavior, we know far less about the sources of these emotions. This paper studies the causes of fear and anger in reaction to a negative stimulus: the financial crisis. Anger should have been experienced among individuals who believed a specific actor was to blame for the crisis. Moreover, individuals should have been particularly angry if they blamed an actor who should be accountable to them, for example the national government. I test these expectations using a panel survey run in Britain between 2005 and 2010. This data shows that British citizens experienced anger if they held an actor responsible for the crisis. Moreover, they felt particularly angry if they held the Labour government (and to a lesser extent the European Union) responsible. These findings underline the importance of studying the causes of emotional reactions and show how these may be linked to common institutional distinctions between political systems. PMID- 26855464 TI - Measuring Acculturation Gap Conflicts among Hispanics: Implications for Psychosocial and Academic Adjustment. AB - This study examined the factor structure and validity of the Acculturation Gap Conflicts Inventory (AGCI), a new instrument developed to measure the types of recurring conflicts that young people experience as part of the parent-child acculturation gap. Participants included 283 Hispanic young adults who completed the AGCI and existing measures of acculturation, family dynamics, psychosocial, and academic adjustment. Principal axis factor analysis revealed three factors with good internal consistency: Autonomy Conflicts, Conflicts over Preferred Culture, and Dating/Being Out Late Conflicts. These factors correlated in the expected direction with acculturative stress and family dynamics variables. Autonomy Conflicts explained more than 25% of the variance in the acculturation gap conflicts items investigated, and this factor demonstrated incremental validity in predicting psychosocial and academic adjustment beyond the variance accounted for by other acculturative stress variables. The AGCI can be valuable to researchers from a variety of disciplines interested in measuring acculturation-related intergenerational conflicts among Hispanic youth that may be predictive of adjustment. PMID- 26855465 TI - Clinical Correlates and Predictors of Caregiver Strain in Children with Chronic Tic Disorders. AB - Although tics are the defining feature of chronic tic disorders (CTD), many children experience comorbid internalizing and externalizing problems that contribute to impairment across several domains, including family functioning. The current study examined clinical correlates and predictors of caregiver strain in parents of children with CTD. Participants were 123 children and adolescents diagnosed with a CTD who participated in a randomized-controlled trial of behavior therapy for reducing tics. Results showed that a combination of disruptive behavior, inattention/hyperactivity, and tic intensity best explained objective strain and a combination of inattention/hyperactivity and tic intensity were the best predictors of subjective caregiver strain. Implications of these findings for care providers are discussed. PMID- 26855466 TI - Register cardiac fiber orientations from 3D DTI volume to 2D ultrasound image of rat hearts. AB - Two-dimensional (2D) ultrasound or echocardiography is one of the most widely used examinations for the diagnosis of cardiac diseases. However, it only supplies the geometric and structural information of the myocardium. In order to supply more detailed microstructure information of the myocardium, this paper proposes a registration method to map cardiac fiber orientations from three dimensional (3D) magnetic resonance diffusion tensor imaging (MR-DTI) volume to the 2D ultrasound image. It utilizes a 2D/3D intensity based registration procedure including rigid, log-demons, and affine transformations to search the best similar slice from the template volume. After registration, the cardiac fiber orientations are mapped to the 2D ultrasound image via fiber relocations and reorientations. This method was validated by six images of rat hearts ex vivo. The evaluation results indicated that the final Dice similarity coefficient (DSC) achieved more than 90% after geometric registrations; and the inclination angle errors (IAE) between the mapped fiber orientations and the gold standards were less than 15 degree. This method may provide a practical tool for cardiologists to examine cardiac fiber orientations on ultrasound images and have the potential to supply additional information for diagnosis of cardiac diseases. PMID- 26855467 TI - Estimation of Tissue Optical Parameters with Hyperspectral Imaging and Spectral Unmixing. AB - Early detection of oral cancer and its curable precursors can improve patient survival and quality of life. Hyperspectral imaging (HSI) holds the potential for noninvasive early detection of oral cancer. The quantification of tissue chromophores by spectral unmixing of hyperspectral images could provide insights for evaluating cancer progression. In this study, non-negative matrix factorization has been applied for decomposing hyperspectral images into physiologically meaningful chromophore concentration maps. The approach has been validated by computer-simulated hyperspectral images and in vivo tumor hyperspectral images from a head and neck cancer animal model. PMID- 26855468 TI - Profile and Morphology of Fungal Aerosols Characterized by Field Emission Scanning Electron Microscopy (FESEM). AB - Fungal aerosols consist of spores and fragments with diverse array of morphologies; however, the size, shape, and origin of the constituents require further characterization. In this study, we characterize the profile of aerosols generated from Aspergillus fumigatus, A. versicolor, and Penicillium chrysogenum grown for 8 weeks on gypsum boards. Fungal particles were aerosolized at 12 and 20 L min-1 using the Fungal Spore Source Strength Tester (FSSST) and the Stami particle generator (SPG). Collected particles were analyzed with field emission scanning electron microscopy (FESEM). We observed spore particle fraction consisting of single spores and spore aggregates in four size categories, and a fragment fraction that contained submicronic fragments and three size categories of larger fragments. Single spores dominated the aerosols from A. fumigatus (median: 53%), while the submicronic fragment fraction was the highest in the aerosols collected from A. versicolor (median: 34%) and P. chrysogenum (median: 31%). Morphological characteristics showed near spherical particles that were only single spores, oblong particles that comprise some spore aggregates and fragments (<3.5 MUm), and fiber-like particles that regroup chained spore aggregates and fragments (>3.5 MUm). Further, the near spherical particles dominated the aerosols from A. fumigatus (median: 53%), while oblong particles were dominant in the aerosols from A. versicolor (68%) and P. chrysogenum (55%). Fiber-like particles represented 21% and 24% of the aerosols from A. versicolor and P. chrysogenum, respectively. This study shows that fungal particles of various size, shape, and origin are aerosolized, and supports the need to include a broader range of particle types in fungal exposure assessment. PMID- 26855469 TI - Effect of the enzymatically modified supported dipalmitoylphosphatidylcholine (DPPC) bilayers on calcium carbonate formation. AB - After an hour contact with a phospholipase A2 (PLA2) solution, only the outer leaflet of the dipalmitoylphosphatidylcholine (DPPC) bilayers supported on mica surface underwent hydrolysis whose products, i.e., palmitic acid and lysophospholipid, accumulated on the bilayer surface. Only calcite was present on the bare mica and enzymatically unmodified and modified supported DPPC bilayers soaked for 2 weeks at 25 and 37 degrees C in a solution of initial pH equals to 7.4 and 9.2 containing calcium and bicarbonate ions at their concentrations about those of human blood plasma. The DPPC bilayers accelerate the crystal growth at lower pH and favors CaCO3 nucleation at higher pH. Enzymatic modification of bilayers does not affect crystal morphology and its organization on the examined surface but causes a slight crystal size increase at lower pH and significantly reduces crystal size at alkaline pH. The temperature increase leads to the formation of bigger crystals under physiological pH and has almost no effect on crystal size at alkaline pH. The obtained results are probably attributed to Ca2+ interaction with a specific polar site on the surface of the membrane and DPPC hydrolysis products acting as nucleation centers. PMID- 26855470 TI - Transient poverty, poverty dynamics, and vulnerability to poverty: An empirical analysis using a balanced panel from rural China. AB - China's economic reforms starting in the late 1970s have resulted in rapid economic growth, with annual growth in gross domestic product averaging greater than 10 percent per year for more than thirty years. Accompanying this rapid growth in national accounts have been rapid and widespread reductions in poverty. With these reductions in poverty, however, there has often been observed an increase in income inequality, both between as well as within rural and urban sectors. This rising income gap challenges the notion that economic reforms in China have been as successful as the poverty statistics would suggest. In this paper, we suggest that an alternative view would be to consider the effects of these reforms on changing the chronic nature of poverty and reducing household vulnerability to poverty. Using a balanced panel from rural China from 1991 through 2006, we find that most poverty among our sample has shifted from being chronic in nature to being transient, with households either shifting into a state of being non-poor moving in and out of poverty. Among our sample, vulnerability to poverty has been declining over time, but the declines are not uniform over time or space. We decompose household vulnerability status into two proximate causes: low expected income and high income variability, finding vulnerability increasingly due to income variability. Additionally, we demonstrate that vulnerable households have very different characteristics than non-vulnerable households. PMID- 26855471 TI - The Stigma Complex. AB - Since the beginning of the twenty-first century, research on stigma has continued. Building on conceptual and empirical work, the recent period clarifies new types of stigmas, expansion of measures, identification of new directions, and increasingly complex levels. Standard beliefs have been challenged, the relationship between stigma research and public debates reconsidered, and new scientific foundations for policy and programs suggested. We begin with a summary of the most recent Annual Review articles on stigma, which reminded sociologists of conceptual tools, informed them of developments from academic neighbors, and claimed findings from the early period of "resurgence." Continued (even accelerated) progress has also revealed a central problem. Terms and measures are often used interchangeably, leading to confusion and decreasing accumulated knowledge. Drawing from this work but focusing on the past 14 years of stigma research (including mental illness, sexual orientation, HIV/AIDS, and race/ethnicity), we provide a theoretical architecture of concepts (e.g., prejudice, experienced/received discrimination), drawn together through a stigma process (i.e., stigmatization), based on four theoretical premises. Many characteristics of the mark (e.g., discredited, concealable) and variants (i.e., stigma types and targets) become the focus of increasingly specific and multidimensional definitions. Drawing from complex and systems science, we propose a stigma complex, a system of interrelated, heterogeneous parts bringing together insights across disciplines to provide a more realistic and complicated sense of the challenge facing research and change efforts. The Framework Integrating Normative Influences on Stigma (FINIS) offers a multilevel approach that can be tailored to stigmatized statuses. Finally, we outline challenges for the next phase of stigma research, with the goal of continuing scientific activity that enhances our understanding of stigma and builds the scientific foundation for efforts to reduce intolerance. PMID- 26855473 TI - Near-field Light Scattering Techniques for Measuring Nanoparticle-Surface Interaction Energies and Forces. AB - Nanoparticles are quickly becoming commonplace in many commercial and industrial products, ranging from cosmetics to pharmaceuticals to medical diagnostics. Predicting the stability of the engineered nanoparticles within these products a priori remains an important and difficult challenge. Here we describe our techniques for measuring the mechanical interactions between nanoparticles and surfaces using near-field light scattering. Particle-surface interfacial forces are measured by optically "pushing" a particle against a reference surface and observing its motion using scattered near-field light. Unlike atomic force microscopy, this technique is not limited by thermal noise, but instead takes advantage of it. The integrated waveguide and microfluidic architecture allow for high-throughput measurements of about 1000 particles per hour. We characterize the reproducibility of and experimental uncertainty in the measurements made using the NanoTweezer surface instrument. We report surface interaction studies on gold nanoparticles with 50 nm diameters, smaller than previously reported in the literature using similar techniques. PMID- 26855472 TI - EXPLORING THE ANTITUMOR EFFECT OF VIRUS IN MALIGNANT GLIOMA. AB - Malignant gliomas are the most common type of primary malignant brain tumor with no effective treatments. Current conventional therapies (surgical resection, radiation therapy, temozolomide (TMZ), and bevacizumab administration) typically fail to eradicate the tumors resulting in the recurrence of treatment-resistant tumors. Therefore, novel approaches are needed to improve therapeutic outcomes. Oncolytic viruses (OVs) are excellent candidates as a more effective therapeutic strategy for aggressive cancers like malignant gliomas since OVs have a natural preference or have been genetically engineered to selectively replicate in and kill cancer cells. OVs have been used in numerous preclinical studies in malignant glioma, and a large number of clinical trials using OVs have been completed or are underway that have demonstrated safety, as well as provided indications of effective antiglioma activity. In this review, we will focus on those OVs that have been used in clinical trials for the treatment of malignant gliomas (herpes simplex virus, adenovirus, parvovirus, reovirus, poliovirus, Newcastle disease virus, measles virus, and retrovirus) and OVs examined preclinically (vesicular stomatitis virus and myxoma virus), and describe how these agents are being used. PMID- 26855475 TI - Redox Zonation and Oscillation in the Hyporheic Zone of the Ganges-Brahmaputra Meghna Delta: Implications for the Fate of Groundwater Arsenic during Discharge. AB - Riverbank sediment cores and pore waters, shallow well waters, seepage waters and river waters were collected along the Meghna Riverbank in Gazaria Upazila, Bangladesh in Jan. 2006 and Oct.-Nov. 2007 to investigate hydrogeochemical processes controlling the fate of groundwater As during discharge. Redox transition zones from suboxic (0-2 m depth) to reducing (2-5 m depth) then suboxic conditions (5-7 m depth) exist at sites with sandy surficial deposits, as evidenced by depth profiles of pore water (n=7) and sediment (n=11; diffuse reflectance, Fe(III)/Fe ratios and Fe(III) concentrations). The sediment As enrichment zone (up to ~700 mg kg-1) is associated with the suboxic zones mostly between 0-2 m depth and less frequently between 5-7 m depth. The As enriched zones consist of several 5 to 10 cm-thick dispersed layers and span a length of ~5-15 m horizontally from the river shore. Depth profiles of riverbank pore water deployed along a 32 m transect perpendicular to the river shore show elevated levels of dissolved Fe (11.6+/-11.7 mg L-1) and As (118+/-91 MUg L-1, mostly as arsenite) between 2-5 m depth, but lower concentrations between 0-2 m depth (0.13+/-0.19 mg L-1 Fe, 1+/-1 MUg L-1 As) and between 5-6 m depth (1.14+/-0.45 mg L-1 Fe, 28+/-17 MUg L-1 As). Because it would take more than a few hundred years of steady groundwater discharge (~10 m yr-1) to accumulate hundreds of mg kg-1 of As in the riverbank sediment, it is concluded that groundwater As must have been naturally elevated prior to anthropogenic pumping of the aquifer since the 1970s. Not only does this lend unequivocal support to the argument that As occurrence in the Ganges-Brahmaputra-Meghna Delta groundwater is of geogenic origin, it also calls attention to the fate of this As enriched sediment as it may recycle As into the aquifer. PMID- 26855476 TI - A Wireless Implantable Micropump for Chronic Drug Infusion Against Cancer. AB - We present an implantable micropump with a miniature form factor and completely wireless operation that enables chronic drug administration intended for evaluation and development of cancer therapies in freely moving small research animals such as rodents. The low power electrolysis actuator avoids the need for heavy implantable batteries. The infusion system features a class E inductive powering system that provides on-demand activation of the pump as well as remote adjustment of the delivery regimen without animal handling. Micropump performance was demonstrated using a model anti-cancer application in which daily doses of 30 MUL were supplied for several weeks with less than 6% variation in flow rate within a single pump and less than 8% variation across different pumps. Pumping under different back pressure, viscosity, and temperature conditions were investigated; parameters were chosen so as to mimic in vivo conditions. In benchtop tests under simulated in vivo conditions, micropumps provided consistent and reliable performance over a period of 30 days with less than 4% flow rate variation. The demonstrated prototype has potential to provide a practical solution for remote chronic administration of drugs to ambulatory small animals for research as well as drug discovery and development applications. PMID- 26855477 TI - Copper-Catalyzed Aerobic C-H Trifluoromethylation of Phenanthrolines. AB - Direct C-H trifluoromethylation of heterocycles is a valuable transformation. In particular, nonprecious metal-catalyzed C-H trifluoromethylation processes, which do not proceed through CF3 radical species, have been less developed. In this cluster report, a new copper-catalyzed aerobic C-H trifluoromethylation of phenanthrolines is described. This transformation affords trifluoromethylated phenanthrolines that have not been synthesized and preliminary mechanistic studies suggest that the CF3 group transfer may occur through cooperative activation. PMID- 26855478 TI - Sandwich-format 3D printed microfluidic mixers: a flexible platform for multi probe analysis. AB - We report on a microfluidic mixer fabrication platform that increases the versatility and flexibility of mixers for biomolecular applications. A sandwich format design allows the application of multiple spectroscopic probes to the same mixer. A polymer spacer is 'sandwiched' between two transparent windows, creating a closed microfluidic system. The channels of the mixer are defined by regions in the polymer spacer that lack material and therefore the polymer need not be transparent in the spectral region of interest. Suitable window materials such as CaF2 make the device accessible to a wide range of optical probe wavelengths, from the deep UV to the mid-IR. In this study, we use a commercially available 3D printer to print the polymer spacers to apply three different channel designs into the passive, continuous-flow mixer, and integrated them with three different spectroscopic probes. All three spectroscopic probes are applicable to each mixer without further changes. The sandwich-format mixer coupled with cost-effective 3D printed fabrication techniques could increase the applicability and accessibility of microfluidic mixing to intricate kinetic schemes and monitoring chemical synthesis in cases where only one probe technique proves insufficient. PMID- 26855479 TI - Self-Control and Grit: Related but Separable Determinants of Success. AB - Other than talent and opportunity, what makes some people more successful than others? One important determinant of success is self-control - the capacity to regulate attention, emotion, and behavior in the presence of temptation. A second important determinant of success is grit - the tenacious pursuit of a dominant superordinate goal despite setbacks. Self-control and grit are strongly correlated, but not perfectly so. This means that some people with high levels of self-control capably handle temptations but do not consistently pursue a dominant goal. Likewise, some exceptional achievers are prodigiously gritty but succumb to temptations in domains other than their chosen life passion. Understanding how goals are hierarchically organized clarifies how self-control and grit are related but distinct: Self-control entails aligning actions with any valued goal despite momentarily more-alluring alternatives; grit, in contrast, entails having and working assiduously toward a single challenging superordinate goal through thick and thin, on a timescale of years or even decades. Although both self control and grit entail aligning actions with intentions, they operate in different ways and at different time scales. This hierarchical goal framework suggests novel directions for basic and applied research on success. PMID- 26855474 TI - Epigenetic Interactions and Gene Expression in Peri-Implantation Mouse Embryo Development. PMID- 26855481 TI - Authors and Contributors in Scientific and Medical Publications. PMID- 26855480 TI - Combined Pharmacotherapy and Cognitive-Behavioral Therapy for Anxiety Disorders: Medication Effects, Glucocorticoids, and Attenuated Treatment Outcomes. AB - Despite the success of both pharmacologic and cognitive-behavioral interventions for the treatment of anxiety disorders, the combination of these modalities in adults has not resulted in substantial improvements in outcome relative to either strategy alone, raising questions about whether there are interfering effects that attenuate the magnitude of combination treatment benefits. In this article, we introduce an accounting of potential interference effects that expands upon arguments asserting the necessity of arousal for successful fear exposure. Specifically, recent advances in the study of the effects of cortisol on memory- suggesting that glucocorticoids are crucial to the learning of emotional material -have led us to posit that the attenuation of glucocorticoid activity by anxiolytic medications may interfere with extinction learning in exposure-based therapies. Implications for the efficacy of combination treatments for the anxiety disorders are discussed. PMID- 26855482 TI - A Critical Review on Clinical Application of Separation Techniques for Selective Recognition of Uracil and 5-Fluorouracil. AB - The most important objectives that are frequently found in bio-analytical chemistry involve applying tools to relevant medical/biological problems and refining these applications. Developing a reliable sample preparation step, for the medical and biological fields is another primary objective in analytical chemistry, in order to extract and isolate the analytes of interest from complex biological matrices. Since, main inborn errors of metabolism (IEM) diagnosable through uracil analysis and the therapeutic monitoring of toxic 5-fluoruracil (an important anti-cancerous drug) in dihydropyrimidine dehydrogenase deficient patients, require an ultra-sensitive, reproducible, selective, and accurate analytical techniques for their measurements. Therefore, keeping in view, the diagnostic value of uracil and 5-fluoruracil measurements, this article refines several analytical techniques involved in selective recognition and quantification of uracil and 5-fluoruracil from biological and pharmaceutical samples. The prospective study revealed that implementation of molecularly imprinted polymer as a solid-phase material for sample preparation and preconcentration of uracil and 5-fluoruracil had proven to be effective as it could obviates problems related to tedious separation techniques, owing to protein binding and drastic interferences, from the complex matrices in real samples such as blood plasma, serum samples. PMID- 26855483 TI - Lipoprotein (a): a Unique Independent Risk Factor for Coronary Artery Disease. AB - The current epidemic affecting Indians is coronary artery disease (CAD), and is currently one of the most common causes of mortality and morbidity in developed and developing countries. The higher rate of CAD in Indians, as compared to people of other ethnic origin, may indicate a possible genetic susceptibility. Hence, Lp(a), an independent genetic risk marker for atherosclerosis and cardiovascular disease assumes great importance. Lp(a), an atherogenic lipoprotein, contains a cholesterol rich LDL particle, one molecule of apolipoprotein B-100 and a unique protein, apolipoprotein (a) which distinguishes it from LDL. Apo(a) is highly polymorphic and an inverse relationship between Lp(a) concentration and apo(a) isoform size has been observed. This is genetically controlled suggesting a functional diversity among the apo(a) isoforms. The LPA gene codes for apo(a) whose genetic heterogeneity is due to variations in its number of kringles. The exact pathogenic mechanism of Lp(a) is still not completely elucidated, but the structural homology of Lp(a) with LDL and plasmin is possibly responsible for its acting as a link between atherosclerosis and thrombosis. Upper limits of normal Lp(a) levels have not been defined for the Indian population. A cut off limit of 20 mg/dL has been suggested while for the Caucasian population it is 30 mg/dL. Though a variety of assays are available for its measurement, standardization of the analytical method is highly complicated as a majority of the methods are affected by the heterogeneity in apo(a) size. No therapeutic drug selectively targets Lp(a) but recently, new modifiers of apo(a) synthesis are being considered. PMID- 26855484 TI - Review and Recommendations for the Component Tests in the Liver Function Test Profile. AB - Pathology laboratories group some tests that they perform on their high throughput biochemistry analysers into profiles of tests that are associated with different organs (e.g. liver function tests-LFT). The components of these profiles are historic and often vary between different laboratories. This can lead to confusion and begs the question of what should be in a particular profile. In community medicine profiles may be used as screening tests but some of the components of the profiles may have low sensitivity and specificity and may produce both false positives and negatives. The LFT may include components which are poor liver function tests but are sensitive to fatty liver and hence elevations may cause unnecessary concern. Harmonisation of clinical chemistry reference intervals and units is occurring now so it is time to consider a similar process for components of a profile. A proposed list of analytes to be performed in the LFT profile is given. PMID- 26855486 TI - Serum Ischemia-Modified Albumin in Preterm Babies with Respiratory Distress Syndrome. AB - Infants with respiratory distress syndrome (RDS) may suffer from severe hypoxia, asphyxia. In this study, we aimed to evaluate serum ischemia-modified albumin (IMA) level as a diagnostic marker for hypoxia in preterm infants with RDS. Thirty-seven premature newborns with RDS were allocated as the study group and 42 healthy preterm neonates were selected as the control group. IMA was measured as absorbance unit (ABSU) in human serum with colorimetric assay method which is based on reduction in albumin cobalt binding. IMA levels were significantly higher in neonates with RDS as compared to the control group (P < 0.001). Cut-off value of IMA (ABSU) was 0.72, the sensitivity level was 91.9 %, the specificity was 78.6 %, positive predictive value was 79.1 % and negative predictive value was 91.7 % at RDS. Area under curve values was 0.93 (P < 0.001; 95 % CI, 0.88 0.98) in the receiver operating characteristic curve. We concluded that elevated blood IMA levels might be accepted as a useful marker for hypoxia in newborn with RDS. PMID- 26855485 TI - Idiopathic Fetal Growth Restriction: Repercussion of Modulation in Oxidative Stress. AB - Oxidative stress has been proposed as one of the causes involved in idiopathic fetal growth restriction (IFGR). However, the exact relationship between oxidative stress and IFGR is not understood. This study aimed at understanding the role of oxidative stress and antioxidant status in IFGR materno-fetal dyads and matched controls. 75 materno-fetal dyads with IFGR were enrolled with equal number of normal low risk controls. Malondialdehyde (MDA) levels were measured as marker of oxidative stress, while paraoxonase-1 (PON1) activity and total antioxidant capacity (TAC) of serum were measured as markers of antioxidant status. MDA levels were increased in both maternal and cord blood of IFGR neonates as compared to controls (p < 0.001). TAC of serum were found to be decreased in IFGR (both maternal and cord blood) as compared to controls (p < 0.001; p < 0.05, respectively). PON1 activity was found to be decreased in the IFGR mothers while it was found increased in IFGR cord blood (p < 0.01; p < 0.001)). IFGR is a state of increased oxidative stress. Decreased PON1 enzymatic activity in mothers is also associated with IFGR. PMID- 26855487 TI - Protective Role of Bilirubin Against Increase in hsCRP in Different Stages of Hypothyroidism. AB - In conjunction with thyroxine, bilirubin may play an important role for regulation of hsCRP level and a consequent pro-inflammatory condition in hypothyroidism. In present study we evaluated the dependence of hsCRP changes on total bilirubin (BT) and fT4 level in thirty overt (OH) and thirty subclinical hypothyroidism (SH). Serum BT, hsCRP, thyroxine and TSH were measured in both groups and compared with forty control subjects. Serum values of TSH, hsCRP showed raised (P < 0.001 for both) values with lower levels for fT4 and BT (P < 0.001 and 0.03 respectively) in hypothyroid patients compared to the controls. ANOVA showed significant increments in TSH and hsCRP values with decreases in fT4 among the control, SH and OH groups respectively (P < 0.001). BT values showed decrease in OH group only in comparison to controls (P = 0.04). Regression analysis revealed that hsCRP was negatively dependent on fT4 (beta = -0.35, P = 0.002) and serum bilirubin (beta = -0.40 and P < 0.001 respectively). Univariate general linear model analysis showed this dependence persisted even when carried out distinctly in SH and OH groups separately (P < 0.001). TSH did not show any significant predictive value on the hsCRP level in either of these two tests. From these analyses we suggest that serum hsCRP is closely integrated to a lowered synthesis of bilirubin and fT4 in hypothyroid patients. Furthermore, this causal relationship is not only limited to overt but also extends to the SH. PMID- 26855488 TI - Status and Interrelationship of Zinc, Copper, Iron, Calcium and Selenium in Prostate Cancer. AB - Deficiency or excess of certain trace elements has been considered as risk factor for prostate cancer. This study was aimed to detect differential changes and mutual correlations of selected trace elements in prostate cancer tissue versus benign prostatic hyperplasia tissue. Zinc, copper, iron, calcium and selenium were analysed in histologically proven 15 prostate cancer tissues and 15 benign prostatic hyperplasia tissues using atomic absorption spectrophotometer. Unpaired two tailed t test/Mann-Whitney U test and Pearson correlation coefficient were used to compare the level of trace elements, elemental ratios and their interrelations. As compared to benign prostatic tissue, malignant prostatic tissue had significantly lower selenium (p = 0.038) and zinc (p = 0.043) concentrations, a lower zinc/iron ratio (p = 0.04) and positive correlation of selenium with zinc (r = 0.71, p = 0.02) and iron (r = 0.76, p = 0.009). Considerably divergent interrelationship of elements and elemental ratios in prostate cancer versus benign prostatic hyperplasia was noted. Understanding of differential elemental changes and their interdependence may be useful in defining the complex metabolic alterations in prostate carcinogenesis with potential for development of element based newer diagnostic, preventive and therapeutic strategies. Further studies may be needed to elucidate this complex relationship between trace elements and prostate carcinogenesis. PMID- 26855489 TI - Biological and Biochemical Potential of Sea Snake Venom and Characterization of Phospholipase A2 and Anticoagulation Activity. AB - This study is designed to isolate and purify a novel anti-clotting protein component from the venom of Enhydrina schistosa, and explore its biochemical and biological activities. The active protein was purified from the venom of E. schistosa by ion-exchange chromatography using DEAE-cellulose. The venom protein was tested by various parameters such as, proteolytic, haemolytic, phospholipase and anti-coagulant activities. 80 % purity was obtained in the final stage of purification and the purity level of venom was revealed as a single protein band of about 44 kDa in SDS-polyacrylamide electrophoresis under reducing conditions. The results showed that the Potent hemolytic activity was observed against cow, goat, chicken and human (A, B and O positive) erythrocytes. Furthermore, the clotting assays showed that the venom of E. schistosa significantly prolonged in activated partial thromboplastin time, thrombin time, and prothrombin time. Venomous enzymes which hydrolyzed casein and gelatin substrate were found in this venom protein. Gelatinolytic activity was optimal at pH 5-9 and (1)H NMR analysis of purified venom was the base line information for the structural determination. These results suggested that the E. schistosa venom holds good promise for the development of novel lead compounds for pharmacological applications in near future. PMID- 26855490 TI - Tumor Necrosis Factor-Alpha, Interleukin-6, C-Reactive Protein Levels and Insulin Resistance Associated with Type 2 Diabetes in Abdominal Obesity Women. AB - We aim to investigate the association between elevated tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and high sensitivity-C-reactive protein (hs-CRP) with type 2 diabetes mellitus (T2DM) in abdominal obesity (AO) women subjects. A total of 428 AO subjects (age 48.4 +/- 10.2 years), and 107 non-AO women subjects (age 48.8 +/- 11.8 years) were enrolled for the all biochemistry testing, inflammatory cytokines, fasting insulin and Homeostasis Model Assessment of insulin resistance (HOMA-IR). Body mass index, waist circumference (WC), blood pressure (BP), plasma glucose (Glu), triglyceride (TG), insulin, HOMA-IR and inflammatory cytokines were significantly higher and lower total antioxidant capacity, HDL-C in AO subjects (p < 0.05). WC was significantly correlated with BP, Glu, TG, LDL-C, insulin, HOMA-IR, TNF-alpha, IL-6 and negative correlation with HDL-C in AO subjects. Elevation of TNF-alpha, IL-6, hs-CRP and insulin resistance were significantly associated with T2DM in AO subjects, after adjusting with insulin resistance, increased oxidative stress, elevated TG and reduced HDL-C by using multiple logistic regression analysis. In conclusions, elevation of inflammatory cytokines, oxidative stress and insulin resistance were associated with T2DM in AO women subjects. These inflammatory cytokines are positively associated with T2DM and may have a causal relation with an increased oxidative stress and insulin resistance in these AO women subjects. PMID- 26855491 TI - A Synergistic Role of Myeloperoxidase and High Sensitivity Troponin T in the Early Diagnosis of Acute Coronary Syndrome. AB - Aim of this study was to evaluate the role of Myeloperoxidase (MPO) and high sensitive Troponin T in the early diagnosis of acute coronary syndrome (ACS). This was a cross sectional study that comprised of 120 individuals of which 75 were cases and 45 healthy controls. On the basis of clinical history and 12 lead electrocardiogram initial diagnosis of ACS was made in the cases. MPO and high sensitive Troponin T (hs-cTnT) was measured in all the individuals. Levels of MPO were significantly higher in patients of ACS as compared to those in control group [medians: 15.40 (95 % CI 11.06-20.84) vs 5.84 (95 % CI 5.50-6.44)]. By taking the cut off as >11.87 U/mL for MPO, its sensitivity was 87 % (95 % CI 73.7 95.1), specificity was 97.3 % (95 % CI 90.6-99.7), positive predictive value was 94.6 % and negative predictive value was 92.6 %. Positive likelihood ratio was 33.0 while negative likelihood ratio was 0.13, whereas the corresponding values in case of hs-cTnT were 95.6 % (95 % CI 85.2-99.5), 61.3 % (95 % CI 49.5-72.6), 59.7 %, 95.8 %, 2.47 and 0.07 by taking cut off as >14 pg/ml. The area under the ROC curves (AUC) of MPO and hscTnT at 0-6 h were 0.971 (95 % CI 0.92-0.99, P < 0.001) and 0.797 (95 % CI 0.71-0.86, P < 0.001) respectively. The logistic model combining the two markers yielded sensitivity, specificity, positive predictive value and negative predictive value of 95.7, 97.3, 98.2 and 93.7 % respectively. It was concluded that MPO and hs-cTnT may be useful tools for risk stratification of ACS and can be used together with better accuracy in the early diagnosis of ACS. PMID- 26855492 TI - Hypoxia-Induced Inflammatory Chemokines in Subjects with a History of High Altitude Pulmonary Edema. AB - High altitude hypoxia is known to induce an inflammatory response in immune cells. Hypoxia induced inflammatory chemokines may contribute to the development of high altitude pulmonary edema (HAPE) by causing damage to the lung endothelial cells and thereby capillary leakage. In the present study, we were interested to know whether chronic inflammation may contribute to HAPE susceptibility. We examined the serum levels of macrophage inflammatory protein-1alpha (MIP-1alpha), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 in group (1) HAPE Susceptible subjects (n = 20) who had past history of HAPE and group (2) Control (n = 18) consist of subjects who had stayed at high altitude for 2 years without any history of HAPE. The data obtained confirmed that circulating MCP-1, MIP 1alpha were significantly upregulated in HAPE-S individuals as compared to the controls suggestive of chronic inflammation. However, it is not certain whether chronic inflammation is cause or consequence of previous episode of HAPE. The moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence of enhanced level of inflammatory chemokines found in this study support the hypothesis that subjects with past history of HAPE have higher baseline chronic inflammation which may contribute to HAPE susceptibility. PMID- 26855493 TI - Troponin T and Heart Type Fatty Acid Binding Protein (h-Fabp) as Biomarkers in Patients Presenting with Chest Pain. AB - Acute coronary syndrome (ACS) is a term for a range of clinical signs and symptoms suggestive of myocardial ischemia. It results in functional and structural changes and ultimately releasing protein from injured cardiomyocytes. These cardiac markers play a major role in diagnosis and prognosis of ACS. This study aims to assess the efficacy of heart type fatty acid binding protein (h FABP) as a marker for ACS along with the routinely used hs-TropT. In our observational study, plasma h-FABP (cut-off 6.32 ng/ml) and routinely done hs Trop T (cutoff 0.1 and 0.014 ng/ml) were estimated by immunometric laboratory assays in 88 patients with acute chest pain. Based on the clinical and laboratory test findings the patients were grouped into ACS (n = 41) and non-ACS (n = 47). The diagnostic sensitivity, specificity, NPV, PPV and ROC curve at 95 % CI were determined. Sensitivity of hs-TropT (0.1 ng/ml), hs-TropT (0.014 ng/ml) and h FABP were 53, 86 and 78 % respectively and specificity for the same were 98, 73 and 70 % respectively. Sensitivity, specificity and NPV calculated for a cut-off combination of hs-TropT 0.014 ng/ml and h-FABP was 100, 51 and 100 % respectively. These results were substantiated by ROC analysis. Measurement of plasma h-FABP and hs-TropT together on admission appears to be more precise predictor of ACS rather than either hs-Trop T or h-FABP. PMID- 26855494 TI - Regional Distribution of Copper, Zinc and Iron in Brain of Wistar Rat Model for Non-Wilsonian Brain Copper Toxicosis. AB - In previous studies, we have reported first in vivo evidence of copper deposition in the choroid plexus, cognitive impairments, astrocytes swelling (Alzheimer type II cells) and astrogliosis (increase in number of astrocytes), and degenerated neurons coupled with significant increase in the hippocampus copper and zinc content in copper-intoxicated Wistar rats. Nonetheless, hippocampus iron levels were not affected by chronic copper-intoxication. Notwithstanding information on distribution of copper, zinc and iron status in different regions of brain due to chronic copper exposure remains fragmentary. In continuation with our previous study, the aim of this study was to investigate the effects of intraperitoneally injected copper lactate (0.15 mg Cu/100 g body weight) daily for 90 days on copper, zinc and iron levels in different regions of the brain using atomic absorption spectrophotometry. Copper-intoxicated group showed significantly increased cortex, cerebellum and striatum copper content (76, 46.8 and 80.7 % increase, respectively) compared to control group. However, non-significant changes were observed for the zinc and iron content in cortex, cerebellum and striatum due to chronic copper exposure. In conclusion, the current study demonstrates that chronic copper toxicity causes differential copper buildup in cortex, cerebellum and striatum region of central nervous system of male Wistar rats; signifying the critical requirement to discretely evaluate the effect of copper neurotoxicity in different brain regions, and ensuing neuropathological and cognitive dysfunctions. PMID- 26855495 TI - Effect of l-Thyroxine on Micronuclei Frequency in Peripheral Blood Lymphocytes in Clinical and Experimental Conditions. AB - The aim was to study the genotoxic effect of high concentration of thyroxine (T4) in vivo in peripheral blood lymphocytes (PBL) of the patients suffering from thyroid disorders. The effect was compared by performing in vitro experiments with addition of increasing concentration of T4 (0.125-1 uM) in whole blood samples from healthy donors. Cytokinesis-blocked micronuclei (CBMN) assay method was used to assess the DNA damage in the PBL. The study included 104 patients which were grouped as control (n = 49), hyperthyroid (n = 31) and hypothyroid (n = 24). A significant increase in micronuclei (MN) frequency was observed in hyperthyroid patients when compared with the hypothyroid and euthyroid group thereby suggesting increased genotoxicity in hyperthyroidism (p < 0.001). A significant increase in MN frequency was observed at T4 concentration of 0.5 uM and above when compared to lower T4 concentrations (0.125 and 0.25 uM) and basal in in vitro experiments (p = 0.000). The results indicate that the T4 in normal concentration does not exhibit the genotoxic effect, as observed in both the in vivo and in vitro experiments. The toxicity of T4 increases at and above 0.5 MUM concentration in vitro. Therefore acute T4 overdose should be handled promptly and effectively so as to avoid the possible genotoxic effect of high concentration of T4 in vivo. PMID- 26855496 TI - Study of Association of Leptin and Insulin Resistance Markers in Patients of PCOS. AB - Polycystic ovary syndrome (PCOS) is a common endocrinological disorder among women of the reproductive age group with long term sequelae which include diabetes mellitus, hypertension and CAD. The present study was conducted to evaluate the association of leptin-an adipokine playing an important role in carbohydrate metabolism and markers of insulin resistance among women with PCOS. Sixty diagnosed cases of PCOS as per Rotterdam criteria were enrolled in this study after informed written consent. Insulin resistance was estimated using the homeostatic model assessment-insulin resistance (HOMA-IR). HOMA-IR was calculated as the product of the fasting plasma insulin value (mU/ml) and the fasting plasma glucose value (mg/dl), divided by 405 and HOMA beta was calculated as 360 * [insulin]/([glucose] - 63) % (glucose in mg/dl). Estimation of serum leptin levels was done by ELISA using leptin ELISA kit from (DRG). A positive correlation of serum leptin levels was observed with markers of insulin resistance. Multiple regression analysis with HOMA-IR as dependent variable demonstrated a statistically significant contribution of fasting insulin levels. This study highlights the role of leptin in alterations in carbohydrate metabolism in patients with PCOS. PMID- 26855497 TI - Hepatic Enzyme's Reference Intervals and Their Modulating Factors in Western Indian Population. AB - The reference intervals (RIs) of serum aminotransferases and Gamma-glutamyl transferase (GGT) have been established many years ago. Recent RIs are not available. The prospective study was conducted to re-evaluate the RIs of liver enzymes and the effect of demographic and anthropometric variables on them in western Indian population. A total of 1059 blood donors comprised the study population. Anthropometry and serum liver enzymes levels were measured. Subjects were categorized into normal weight and overweight by using body mass index (BMI) and waist circumference (WC). For RI determination, non-parametric methodology recommended by IFCC/CLSI was adopted. Mann-Whitney test and Spearman's rank correlation were used for statistical analysis. Upper limit of normal reference value of liver enzymes were lower in female compared to male. (ALT-23.55 F vs 36.00 M, GGT-34.58 F vs 36.20 M) When RI of liver enzymes were calculated according to body mass index, the upper limit of normal of ALT and GGT were higher in overweight group compared to normal weight group. (ALT-38.00 vs 27.00 IU/L and GGT-37.59 vs 35.26 IU/L). In both male and female, liver enzymes correlated significantly with age. WC and BMI were positively correlated with AST, ALT and GGT in both subgroups and the correlation was stronger in male. Demographic factors should be considered for making liver enzyme tests more clinically relevant. Gender based partitioning should be adopted for serum alanine aminotransferase (ALT) and GGT reference values for Western Indian population. PMID- 26855498 TI - Carbohydrate Deficient Transferrin and Interleukin-6 as Predictors of Fibrosis in Alcohol Cirrhosis. AB - The severity of alcoholic cirrhosis depends on the presence of liver inflammation and fibrogenesis. Previous studies have hypothesized that carbohydrate deficient transferrin can be used as marker of liver impairment in alcoholic liver disease patients. The present study was designed to assess whether carbohydrate deficient transferrin is associated with procollagen III peptide and predict fibrosis in alcohol cirrhosis patients. We enrolled 48 patients with alcoholic cirrhosis and 38 healthy controls. Serum carbohydrate deficient transferrin, procollagen III peptide and interleukin-6 levels were estimated in both groups. Serum carbohydrate deficient transferrin, procollagen III peptide and interleukin-6 were significantly increased in alcoholic cirrhosis patients compared to controls. Stepwise regression analysis showed that carbohydrate deficient transferrin (adjusted R(2) = 0.313, beta = 0.362, p = 0.003) and interleukin-6 (adjusted R(2) = 0.194, beta = 0.459, p = 0.001) were positively associated with procollagen III peptide when age, duration and amount of alcohol consumption were considered as covariates. We conclude that elevated carbohydrate deficient transferrin and interleukin-6 act as predictors of fibrosis in alcoholic cirrhosis. PMID- 26855500 TI - Changing Times for the IJHBT. PMID- 26855499 TI - Hypogonadotropic Hypogonadism and Gynaecomastia in the Young Adult: A Case Series. AB - We present three cases who presented to our Endocrinology OPD a few days apart with the common complaints of no or minimal development of secondary sexual characteristics. Although they had similar problems, investigations revealed a spectrum of different clinical, biochemical and genetic abnormalities. All the patients had otherwise normal anterior pituitary hormone secretion and sellar anatomy. One had a short Y chromosome, one was a Klinefelter syndrome and the other had no chromosomal abnormality. These findings along with absence of any detectable abnormality on pituitary imaging helped us diagnose these cases as Idiopathic hypogonadotropic hypogonadism. Treatment with testosterone showed marked improvement at 1 year follow up. PMID- 26855501 TI - Multiple Myeloma: Treatment is Getting Individualized. AB - Multiple myeloma (MM) is a heterogeneous disease with varied outcome. The novel agents including two major classes of drugs; the immunomodulatory drugs and the proteasome inhibitors with unprecedented response rates, have replaced conventional chemotherapy. With monoclonal antibodies on the horizon, outcome of this disorder will further improve. Progression in risk stratification systems has made it possible to predict the disease course as well as outcome in myeloma patients with disease categorization into low to high risk. In addition, detection of minimal residual disease by serum free light chain assay, flow cytometry, molecular techniques like polymerase chain reaction and positron emission tomography scan is playing an important role in modifying the treatment. An extensive research in the disease biology has improved our knowledge regarding interplay between myeloma cells and elements of the bone marrow microenvironment which contribute to sustain proliferation and survival as well as de novo drug resistance. Again, insight into the role of genetic and epigenetic interactions in MM has exposed new molecular targets. All these have opened the gateway for novel therapeutic strategies with focus on risk based individualized therapy. PMID- 26855502 TI - Old but Still Relevant: High Resolution Electrophoresis and Immunofixation in Multiple Myeloma. AB - INTRODUCTION: High resolution electrophoresis (HRE) and immunofixation (IFX) of serum and urine are integral to the diagnostic work-up of multiple myeloma. Unusual electrophoresis patterns are common and may be misinterpreted. Though primarily the responsibility of the hematopathologist, clinicians who are responsible for managing myelomas may benefit from knowledge of these. In this review article we intend to discuss the patterns and importance of electrophoresis in present day scenario. METHODS: Patterns of HRE and IFX seen in our laboratory over the past 15 years were studied. RESULTS: Monoclonal proteins are seen on HRE as sharply defined bands, sometimes two, lying from gamma- to alpha-globulin regions on a background of normal, increased or decreased polyclonal gamma-globulins, showing HRE to be a rapid and dependable method of detecting M-protein in serum or urine. Immunofixation complements HRE and due to its greater sensitivity, is able to pick up small or light chain bands, not apparent on electrophoresis, including biclonal disease even when electrophoresis shows only one M-band. Special features liable to misinterpretation are discussed. Familiarity with the interpretation of the varied patterns seen in health and disease is essential for providing dependable laboratory support in the management of multiple myeloma. PMID- 26855503 TI - Current Role of Genetics in Hematologic Malignancies. AB - Rapidly changing field of genetic technology and its application in the management of hematological malignancies has brought significant improvement in treatment and outcome of these disorders. Today, genetics plays pivotal role in diagnosis and prognostication of most hematologic neoplasms. The utilization of genetic tests in deciding specific treatment of various hematologic malignancies as well as for evaluation of depth of treatment response is rapidly advancing. Therefore, it is imperative for practitioners working in the field of hemato oncology to have sufficient understanding of the basic concepts of genetics in order to comprehend upcoming molecular research in this area and to translate the same for patient care. PMID- 26855504 TI - Chronic Graft Versus Host Disease in Acute Leukemia Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplant: Analysis of Risk Factors, Pattern and Long Term Outcome. AB - Chronic graft versus host disease (cGVHD) is a common late complication of allogenic hematopoietic stem cell transplant (HSCT). We analyzed risk factors, pattern and long term transplant outcomes of cGVHD at a tertiary cancer centre. Seventy-seven consecutive patients who underwent HSCT for acute leukemia were included. Forty (52 %) patients developed cGVHD; 24 (60 %) extensive stage while 16 (40 %) limited stage. Oral cavity was the commonest site of involvement (25 patients) followed by liver, skin and lung. We found that female donor to male recipient transplant and diagnosis of acute lymphoblastic leukemia (ALL) were the only factors associated with increased risk of cGVHD. The incidence of leukemia relapse was 18 % in patients who developed cGVHD compared to 51 % in those who did not (P = 0.002). Four year overall survival and relapse free survival (RFS) were 62 and 46 % in patients who developed cGVHD compared to 29 % (P < 0.001) and 29 % (P < 0.001) in patients who did not develop cGVHD, respectively. We conclude that cGVHD is more common in male patients with female donors and in patients transplanted for ALL. Oral cavity is the commonest site of cGVHD in our patients and transplant related survival outcomes are superior in patients who develop cGVHD. PMID- 26855505 TI - Growth in Children Treated for Acute Lymphoblastic Leukemia: Single Institution Report from North India. AB - Survivors of childhood leukemia are at risk of impaired growth and short stature as adults due to intensive combination chemotherapy and radiation injury. This study was undertaken to evaluate anthropometry in children treated for acute lymphoblastic leukemia (ALL). Children treated for ALL and off treatment for a minimum period of 2 years were evaluated for height, weight and BMI. Z scores were calculated for height, weight and BMI: at induction, 6 months after starting treatment, at end of treatment and at 2 years after completion of therapy. Change in z scores were calculated and compared with CDC criteria and Agarwal standards for Indian children. Fifty two boys and 21 girls were analyzed. Height and weight z scores were seen to show a steep decrease during the initial intensive phase of therapy. The gain in height and weight continued to be slow during therapy and catch up occurred after cessation of therapy. On completion of therapy, patients were shorter, but not significantly so. Girls <9 years were significantly shorter. Weight remained on the lower side of normal. Change of z scores was statistically significant for weight at end of treatment (p = 0.032) and 2 years after completion of treatment (p = 0.00). BMI z score increased throughout the study period. Peak growth velocities were also late in the study subjects Anthropometric variables of height, weight and BMI are affected by ALL during therapy. Growth deceleration is maximum during the intensive phase of therapy. Catch up growth occurs but children remain smaller than their peers. PMID- 26855506 TI - Low Dose Cytosine Arabinoside and Azacitidine Combination in Elderly Patients with Acute Myeloid Leukemia and Refractory Anemia with Excess Blasts (MDS-RAEB2). AB - Only one-third of elderly (>60 years) AML and MDS-RAEB2 patients may receive intensive chemotherapy treatment alternatives that are limited in this patient group due to the potential of severe toxicity. Previous studies have shown that azacitidine and low dose cytarabine treatments may be a beneficial treatment option for these patients. In this study, we aimed to good results with low toxicity in elderly patients. We retrospectively analyzed the AML and MDS-RAEB2 patients who received azacitidine monotherapy and azacitidine and LDL-ara-c combination therapy for a comparison of their response to therapy, survival rates, and toxicity rates and for determining the factors that could affect their overall survival. A total of 27 patients who were diagnosed with de novo AML and MDS-RAEB2 and who received at least four cycles of chemotherapy were included in the study, and the data were evaluated retrospectively. When monotherapy and combination therapy groups were compared, the pretreatment bone marrow blast count was observed to be greater in the combination therapy group. A statistically significant difference was not detected between the groups regarding the response to therapy ratios (p = 0.161) (42.9 and 57.1 %, respectively). No difference was detected between the groups regarding therapy related toxicity. Infections were the most common complication. Progression-free survival was 30.3 % for the azacitidine monotherapy group and 66.7 % for the combination (azacitidine + LD-ara-c) group. The factors influencing the overall survival rate were determined based on the response to the first-line therapies, more than a grade 2 infection, fever, and relapse in a multi-variance analysis. The combination therapy may be a well-tolerated treatment option for the elderly, vulnerable AML patients whose blast count is high in response to therapy rates, overall survival rates, and toxicities are not different, although the pre treatment bone marrow blast count was greater in the combination therapy groups compared with the monotherapy group. PMID- 26855507 TI - Changes of Apolipoprotein M Gene Expression During the Cell Differentiation and Apoptosis Induced by Simvastatin in Combination with All-Trans Retinoic Acid in Human Promyelocytic Leukemia Cell Line NB4. AB - We examined the effect of simvastatin (SV) alone and in combination with all trans retinoic acid (ATRA) on proliferation, differentiation, apoptosis and apolipoprotein M (apoM) expression in the human promyelocytic leukemia cell line NB4. The NB4 cells were incubated with 10 MUM Simvastatin (10SV) and 0.5 MUM ATRA alone or in combination, taking NB4 cells without any treatment as normal controls. The cells of different groups were collected at 24, 48 and 72 h post incubation for further detection. Their morphological changes were observed after Wright stain. MTT method was used to assay the growth inhibition rate and flow cytometry to detect CD11b expression level and the early stage apoptosis ratio. Real-time quantitative reverse transcriptase-polymerase chain reaction was used to detect the apoM gene expression levels. As expected 0.5 MUM ATRA did not affect proliferation or apoptosis, strongly induced differentiation and decreased apoM expression. 10SV inhibited proliferation, increased apoptosis, induced differentiation and increased apoM expression in a time-dependent manner. The addition of ATRA to SV did not increase the effect of SV on proliferation and apoptosis, but increased the effect of SV on differentiation. And completely abrogated the effect of SV on apoM expression. Together these results show that SV has anti-leukemic properties by itself and that combined therapy may have a place in the current anti-leukemic arsenal. PMID- 26855508 TI - Obstetric Complications and Management in Chronic Myeloid Leukemia. AB - Chronic myeloid leukaemia (CML) is amongst the most common haematological malignancies encountered in adults. The younger age of onset and increased incidence of CML in Indians leads to higher chances of encountering it in pregnancy. Pregnancy in CML is a complex situation as first line therapy with tyrosine kinase inhibitors (TKI), is fraught with multiple fetal safety issues. The fetal aspects have been elucidated in literature, but there is scarcity of information on the obstetric outcome per se in presence of CML, excluding the influence of TKI. Obstetric outcomes of 5 pregnancies in four patients with CML are being reported. Literature on interplay of CML and bleeding or thrombotic manifestations is reviewed. The major complications encountered were antepartum (APH) and postpartum haemorrhage (PPH), preterm labour, intrauterine growth retardation and intrauterine fetal death. Patients in the reproductive age group with diagnosis of CML should be carefully counseled regarding the effect of disease and TKI on the maternal-fetal health. Bleeding complications, particularly APH and PPH may be encountered in CML patients. Close coordination of the obstetrician, haematologist, and neonatologist is required in managing these cases successfully. The need for absolute contraception till the remission of disease needs to be emphasized for further pregnancies. PMID- 26855509 TI - Apoptosis, DAP-Kinase1 Expression and the Influences of Cytokine Milieu and Mesenchymal Stromal Cells on Ex Vivo Expansion of Umbilical Cord Blood-Derived Hematopoietic Stem Cells. AB - Expansion of umbilical cord blood-derived CD34(+) cells can potentially provide them in numbers sufficient for clinical applications in adult humans. In this study apoptosis rate of expanded cells, mRNA expression and promoter methylation status of DAPK1 were evaluated during cord blood hematopoietic stem cell (CB-HSC) ex vivo expansion using cytokines and a co-culture system with mesenchymal stromal cells (MSCs). Ex vivo cultures of CB-HSCs were performed in three culture conditions for 14 days: cytokines with MSCs feeder layer, cytokines without MSCs feeder layer and co-culture with MSCs feeder layer without cytokine. Total number of cells, CD34(+) cells and colony forming unit assay were performed during expansion. Flow cytometric analysis by propidium iodide was performed to detection of apoptosis rate in expanded cells. Methylation status of the DAPK1 gene promoter was analyzed using methylation specific PCR, and DAPK1 mRNA expression was evaluated by real time-PCR. Maximum CB-CD34(+) cells expansion was observed in day 10 of expansion. The highest apoptosis rate was observed in cytokine culture without feeder layer that showed significant difference with co culture condition. The data showed that ex vivo expansion of CD34(+) cells in all three culture conditions after 10 days resulted in, significant increased expression of DAPK1, also a significant difference between co-culture without cytokine and two other cytokine culture was observed (p < 0.01). DAPK1gene promoter of expanded CD34(+) cells at days 5, 10 and 14 of culture remained in unmethylated form similar to fresh CD34(+) cells. Expression of DAPK1 in hematopoietic cells was increased during 10 days expansion of CD34(+) cells. Also no methylation of DAPK1 promoter was observed; otherwise it would be capable of initiating some leukemic cell progression or disruption in hematopoietic regeneration. PMID- 26855510 TI - Sevelamer is an Effective Drug in Treating Hyperphosphatemia Due to Tumor Lysis Syndrome in Children: A Developing World Experience. AB - We report here a study on efficacy of sevelamer hydrochloride in treating hyperphosphatemia due to tumor lysis syndrome (TLS) in a developing world setting. Twenty one children with hyperphosphatemia due to TLS were included. All received hyper-hydration, allopurinol and sevelamer. Efficacy was assessed by decrease in serum phosphate level, calcium-phosphate product and TLS score as per Cairo Bishop definition. Four children who underwent dialysis were excluded from analysis. Among the remaining 17 patients with hyperphosphatemia, laboratory TLS was recorded in 15 patients and clinical TLS in five. Sevelamer was given according to weight, most often 400 mg twice to thrice daily. Mean phosphatemia decreased from 8.3 +/- 3.0 to 6.7 +/- 2.1 mg/dl within 24 h of starting sevelamer (p = 0.02), 6.0 +/- 2.1 mg/dl at 48 h, 4.9 +/- 1.5 mg/dl at 72 h and 4.39 +/- 1.7 mg/dl at 96 h. TLS was corrected in 72 h in 14 patients, 96 h in 1 and 120 h in another patient. Mean calcium-phosphate product decreased from 63.0 +/- 14.0 to 49.2 +/- 9.7 mg/dl (p = 0.002) at 24 h, 46.1 +/- 17.0 mg/dl at 48 h and 39.7 +/- 13.5 mg/dl at 72 h. There was no mortality due to hyperphosphatemia. Sevelamer is efficacious in children with malignancy-associated hyperphosphatemia in the developing world. PMID- 26855511 TI - A Prospective Study of Adequacy of Anticoagulation with Fixed Dose Weight Adjusted Unfractionated Heparin in Patients with Deep Vein Thrombosis. AB - Weight adjusted fixed dose subcutaneous unfractionated heparin (UFH) is one of the options for the treatment of deep vein thrombosis (DVT), but the degree of its anticoagulant effect has not been tested in India. This was a prospective observational study, conducted at a tertiary care hospital in South India between September 2012 and March 2014. DVT was diagnosed using compression ultrasonography. UFH was given as an initial loading dose of 333 U/kg followed by a maintenance dose of 250 U/kg twice daily subcutaneously. aPTT was done on day 2 and day 4 after 6 h of the morning dose of heparin. Patients were categorized based on aPTT ratios. Fifty five patients treated for proximal lower limb DVT had received UFH. Their median age was 41 years. DVT was secondary to malignancy, immobilisation or pro-coagulant state. No obvious etiology was found in 47 % of the patients. The mean aPTT on day 2 was 41.8 s and 51.7 s on day 4. The aPTT ratio was subtherapeutic in 63.6 % and therapeutic in 32.7 % of the patients on day 2. Five patients had adverse events in the hospital. Three patients died and two other patients had confirmed pulmonary embolism. Death was due to pulmonary embolism in one patient and metastatic malignancies in the other two. No bleeding manifestation had occurred. Caution is required in implementing this UFH regimen as this preliminary investigation has found predominantly subtherapeutic aPTT ratios during the initial phase of anticoagulation. PMID- 26855512 TI - The Effect of Carbon Dioxide Insufflation Applied at Different Pressures and Periods on Thrombotic Factors. AB - The aim of this experimantal study which is applied on rats, is to determine the differences on the clotting factors over the application of low and high intraabdominal pressure (IAP) values in different periods of time in carbon dioxide (CO2) pneumoperitoneum. Thirty rats were randomized into five groups (n = 6): a control group (Group K) and 1 h and 6 mm Hg IAP (Group A), 2 h and 6 mm Hg IAP (Group B), 1 h and 12 mm Hg IAP (Group C) and 2 h and 12 mm Hg IAP were created with CO2 pneumoperitoneum (Group D). At the end of the experiment, plasma samples taken from subjects and fibrinogen, FII (prothrombin), FV, FVII, FVIII, FIX, FX, FXI, FXII, von willebrand's factor (vWF), ristocetin cofactor, protein C, protein S, antithrombin III (AT III) levels are studied. There were statistically significant differences in the mean levels of FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, and protein S between the groups. A hypercoagulable state occurred with the following: increase in the coagulation parameters compared to the control group; increase in FVII in the group only Group C; decrease in AT III in all groups compared to the control group; decrease in protein C in the group only XII Group D compared to control group; decrease in protein S in all groups except group D compared to control group. CO2 insufflation predisposes to thromboembolic events both by inducing coagulation factors and by suppressing the fibrinolytic system contrary to the controversies in the literature. PMID- 26855513 TI - Enhancement of Antibody Titre and Development of Additional Red Cell Alloantibodies Following Intrauterine Transfusion. AB - Intrauterine blood transfusion is the mainstay of managing foetuses with severe anemia. It may however result in fetomaternal hemorrhage, which in cases of Rh isoimmunisation may increase the severity of the disease by enhancing the maternal immunological response to fetal antigens. This study was conducted to determine the frequency, specificity and origin of additional red cell antibodies which developed after IUT. The change in the titre of allo anti-D following IUT was also determined. Antibody detection and titration was done on the blood samples of all the patients before and after intrauterine blood transfusion to check for the development of additional antibody and change in the titre of existing anti-D. Severe anemia was found in 17 (58.6 %) fetuses who received a total of 42 ultrasound-guided IUTs. Development of antibodies additional to anti D in maternal serum was seen in 5 (29.4 %) cases. The specificity of additional alloantibodies was anti-C in four cases whereas it was anti-E in one case. Four fold or greater increase in existing allo-anti D titre was seen in 6 (35.3 %) cases after IUT. Enhancement of maternal sensitisation leading to an increase in maternal antibody titre is particularly seen after the first IUT. Matching of the donor RBCs particularly for Rh antigens might prevent the induction of additional alloantibodies against these antigens. IUT as a treatment modality should be given judiciously and only when the need is inevitable. PMID- 26855514 TI - Serological Assessment for Leishmania donovani Infection in Blood Donors of Sunsari District, Dharan, Nepal. AB - Visceral leishmaniasis (VL) is a major vector-borne disease caused by Leishmania donovani, after replication of the parasites in macrophages, mononuclear phagocytic system. VL is endemic in 12 districts of central and eastern Terai lowlands of Nepal bordering North Bihar, India with an estimated 8 million population at risk. In addition, VL endemicity is also extending to new endemic regions like Dharan from its classical rural foci. Hence, we aimed to detect the evidence of Leishmania donovani infection in the blood samples received from blood donors of Sunsari district, Dharan, (eastern Nepal), a region endemic for human VL. Sera from 507 asymptomatic blood donors were subjected to serological screening for anti-Leishmania donovani antibodies. Direct agglutination test (DAT) was performed on the sera. Out of 507 donors, majority (78.50 %) were male. Among the donors, 472 (93.10 %) belonged to age group 18-45 years where as 35 (6.90 %) to age group >45 years. Circulating anti-Leishmania antibodies were detected in 5 (1 %) out of 507 healthy, Human Immunodeficiency Virus types 1 and 2 (HIV 1and 2), Hepatitis B Surface Antigen (HBsAg), anti- Hepatitis C Virus (anti-HCV)-negative, and Syphillis non-reactive donors. All the seropositive cases were male and belonged to the age group 18-45 years. The result suggests that there is an immediate need of screening asymptomatic blood donors for leishmania seropositivity especially in endemic areas. PMID- 26855515 TI - Study of Methaemoglobin in Malaria Patients. AB - To estimate the concentration of methemoglobin (MetHb) in malaria patients and correlate with severity of malaria infection. This prospective study included 30 untreated cases of malaria confirmed by Quantitative Buffy Coat (QBC) test and 30 age sex matched non-malarial cases taken as controls. All the patients underwent thorough clinical examination and routine biochemical investigation. Methemoglobin levels were estimated by spectrophotometric (co-oxymeter) method on day 1 and day 10 of diagnosis of all study group patients and correlated with clinical profile and severity. Out of 30 malaria patients 22 were males and eight were females. The clinical presentations in complicated malaria group (n = 21) were fever 21 (100 %), anemia 17 (80.95 %), renal failure 12 (52.38 %) and coma/convulsion 5 (23.8 %). The mean age of the study group was 41.66 years. Mean MetHb in complicated malaria on day 1 was 2.55 +/- 1.75 % and day 10 was 10.69 +/ 8.19 % (statistically significant). The overall mortality was 13 (43.33 %) among study group while 5 (16.66 %) was found among control group. Mean MetHb who died (n = 13) on day 1 was 3.144 +/- 1.829 % and (n = 8) on day 10 it was 19.982 +/- 8.406 %. Increase in level of methaemoglobin is detrimental to the body and is associated with increase in mortality. Routine MetHb estimation may be used as a prognostic indicator in the management of malaria patients. It is suggested that addition of drugs which reduce MetHb may be tried along with antimalarial drugs to decrease morbidity and mortality in malaria. PMID- 26855517 TI - Marital Status and Fertility in Adult Iranian Patients with beta-Thalassemia Major. AB - Expecting a family is an important component and a great goal for better quality of life for most of adults with beta-thalassemia major. The aim of the present study was to examine the marital status of adults with beta-thalassemia major. This cross-sectional study examined the marital status of patients with transfusion-dependent beta-thalassemia aged over 15 years. Patients' demographic characteristics including age, gender, marital status, duration of marriage, divorce, having or not having children and spouse's health status were recorded. Information about the disease including cardiac and endocrine complications, ferritin level, splenectomy and viral hepatitis were also recorded. Of 228 patients with transfusion-dependent beta-thalassemia major aged over 15 years who were treated at this medical center, 32 (14 %) were married. The mean age of married patients was 25.18 +/- 4.74 years. Among the married patients, 8 (25 %) were females and 24 (75 %) patients were males. The mean age of marriage was 22.76 +/- 4.16 years. The minimum and maximum marriage age was 15 and 33 years, respectively. The median duration of marriage was one year with the range from 3 months to 11 years. Only 8 (25 %) patients (one female and seven males) had children. Therapeutic advances have led to significantly increased survival and improved quality of life and fertility of patients with beta-thalassemia major. According to the results, 14 % of patients over 15 years were married which was slightly higher as compared with other similar studies. PMID- 26855516 TI - The Effect of Hydroxyurea Therapy in Bahraini Sickle Cell Disease Patients. AB - Hydroxyurea (HU) is used as a disease-modifying agent in sickle cell disease (SCD). Its beneficial effects have been ascribed to inhibition of the sickling process through increase of fetal hemoglobin (HbF) levels and influence on multiple factors affecting adhesion of erythrocytes to vascular endothelium. The present study investigates the effect of HU in SCD patients who were grouped on the basis of association with alpha- and beta-thalassemia using routine laboratory methods. A retrospective cross-sectional chart-review was done of 51 adult Bahraini SCD patients attending Salmaniya Medical Complex, Bahrain. Four sub-groups of cases were identified: (i) homozygous sickle cell anemia, 24 cases; (ii) SCD with microcytosis, 16 cases; (iii) sickle alpha-thalassemia, seven cases; and (iv) sickle beta thalassemia, four cases. Documented laboratory and clinical data included hemoglobin level (Hb), hematocrit (Hct), red cell indices, hemoglobin fractions, hospital admissions (frequency), number of inpatient-days, pain episodes (frequency) and red cell transfusion requirement (number of units). Pre- and post-treatment data were compared. Hydroxyurea treatment led to highly significant reduction of HbS % and pain crisis episodes in all patient groups. Other changes such as increases of total hemoglobin, Hct and HbF and reduction of hospital admissions, inpatient days and red cell units transfused also occurred but with less consistent levels of significance within patient sub-groups. Treatment with HU is beneficial for all subgroups of Bahraini SCD patients, without or with alpha- and beta-thalassemia interactions. PMID- 26855518 TI - Fetal Hemoglobin in Tunisian Sickle Cell Disease Patient: Relationship with Polymorphic Sequences Cis to the beta-Globin Gene. AB - Fetal hemoglobin (HbF) plays a dominant role in ameliorating morbidity and mortality of hemoglobinopathies. We evaluated the effects of polymorphic markers within the beta-globin gene cluster to identify the genetic mechanics that influence HbF on Tunisian sickling patients (n = 242). Haplotype analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the framework polymorphism was established by PCR-sequencing, four independent regions of interest were identified: the 5' region of beta-LCR-HS2 site, the intervening sequence II (IVSII) region of two fetal (Ggamma and Agamma) genes and the 5' region of beta-globin gene. The correlation of these various Haplotypes and SNPs with HbF expression and clinical data was studied. Our data showed that among the various polymorphic markers analyzed, only the sequence (AT)xN12(AT)y in LCR HS2 region was significantly associated (p < 0.05) with increased HbF levels, suggesting that the beta-globin gene cluster exerts a significant effect on HbF in sickle cell patients. This study can improve understanding of the physiopathology of the disease and aid to increase our ability to predict clinical severity. PMID- 26855519 TI - Commentary on Elective versus therapeutic neck dissection in node-negative oral cancer. PMID- 26855520 TI - Indian Council of Medical Research consensus document for the management of tongue cancer. AB - The document is based on consensus among the experts and best available evidence pertaining to Indian population and is meant for practice in India.Early diagnosis is imperative in improving outcomes and preserving quality of life. High index of suspicion is to be maintained for leukoplakia (high risk site).Evaluation of a patient with newly diagnosed tongue cancer should include essential tests: Magnetic resonance imaging (MRI) is investigative modality of choice when indicated. Computed tomography (CT) scan is an option when MRI is unavailable. In early lesions when imaging is not warranted ultrasound may help guide management of the neck.Early stage cancers (stage I & II) require single modality treatment - either surgery or radiotherapy. Surgery is preferred. Adjuvant radiotherapy is indicated for T3/T4 cancers, presence of high risk features [lymphovascular emboli (LVE), perineural invasion (PNI), poorly differentiated, node +, close margins). Adjuvant chemoradiation (CTRT) is indicated for positive margins and extranodal disease.Locally advanced operable cancers (stage III & IVA) require combined multimodality treatment - surgery + adjuvant treatment. Adjuvant treatment is indicated in all and in the presence of high risk features as described above.Locally advanced inoperable cancers (stage IVB) are treated with palliative chemo-radiotherapy, chemotherapy, radiotherapy, or symptomatic treatment depending upon the performance status. Select cases may be considered for neoadjuvant chemotherapy followed by surgical salvage.Metastatic disease (stage IVC) should be treated with a goal for palliation. Chemotherapy may be offered to patients with good performance status. Local treatment in the form of radiotherapy may be added for palliation of symptoms.Intense follow-up every 3 months is required for initial 2 years as most recurrences occur in the first 24 months. After 2(nd) year follow up is done at 4 6 months interval. At each follow up screening for local/regional recurrence and second primary is done. Imaging is done only when indicated. PMID- 26855521 TI - Clinical trials in oncology: Has India come of age? PMID- 26855522 TI - Neoadjuvant chemotherapy in oral cancers: Selecting the right patients. AB - The standard of care treatment for oral squamous cell carcinoma (OSCC) at present, consist of surgical resection followed by adjuvant radiotherapy and chemotherapy as indicated. Despite recent advances the overall prognosis remains guarded. Role of neoadjuvant chemotherapy is being explored with premise of reducing extent of surgical resection, improving loco-regional control and decreasing distant metastasis, thereby improving treatment outcomes by decreasing mortality and morbidity. However, indications of neoadjuvant chemotherapy in oral cancers are not clearly defined. Majority of studies have failed to demonstrate a significant benefit of neoadjuvant chemotherapy in terms of loco regional control and overall survival in resectable OSCC. In a select subset of patients with locally very advanced and unresectable OSCC, neoadjuvant chemotherapy has been shown to cause tumor shrinkage and improve resectability. These hypothesis generating findings of reduction in distant metastasis, improved resectability and functional outcome, however need further validation. In summary, the role of neoadjuvant chemotherapy for OSCC remains investigational and has a limited role outside clinical trial. PMID- 26855523 TI - Epidemiological review of laryngeal cancer: An Indian perspective. AB - BACKGROUND: Laryngeal cancer is one of the 10 leading causes of cancer in Indian men. The association of laryngeal cancer and tobacco smoking is well-established, but the peculiarities such as wide variation of disease distribution and survival, role of tobacco chewing, indoor air pollution, and dietary factors in laryngeal cancer causation needs to be understood. In this study, we review the descriptive and observational epidemiology of laryngeal cancer in India. MATERIALS AND METHODS: MEDLINE and Web of science electronic database was searched from January 1995 to December 2013, using the using keywords "laryngeal cancer, laryngeal cancer outcome, epidemiology, etiological factor and their corresponding Mesh terms were used in combination like OR, AND." Two authors independently selected studies published in English and conducted in India. A total of 15 studies were found to be relevant and eligible for this review. RESULTS: In India, laryngeal cancer contributes to approximately 3-6% of all cancers in men. The age-adjusted incidence rate of cancer larynx in males varies widely among registries, highest is 8.18 per 100,000 in Kamprup Urban District and the lowest is 1.26 per 100,000 in Nagaland. The 5-year survival for laryngeal cancer in India is approximately 28%. Indian studies show tobacco, alcohol, long term exposure to indoor air pollution, spicy food, and nonvegetarian diet as risk factors for laryngeal cancer. CONCLUSION: There is wide regional variation in the incidence of laryngeal cancer in India. Survival rates of laryngeal carcinoma are much lower as compared to other Asian countries. Studies conducted in India to identify important risk factors of laryngeal cancer are very limited, especially on diet and indoor air pollution. Hence, more research is required for identifying the etiological factors and development of scientifically sound laryngeal cancer prevention programs. PMID- 26855524 TI - Metronomic chemotherapy in platinum-insensitive failures and/or early failures postmultimodality management in oral cancers. AB - PURPOSE: Oral cancer patients with platinum-resistant disease and or early failures have limited treatment options. This analysis was planned to study the efficacy of metronomic chemotherapy in this group of patients. MATERIALS AND METHODS: This was a retrospective analysis of oral cancer patients who had squamous cell carcinoma and had an early failure and/or platinum-insensitive failure. Early failure was defined as a failure either within 1-month of adjuvant radiotherapy or within 6 months of chemoradiation (CTRT). A sample size of 100 patients was selected for this study. If >=39 of 100 patients would have survived at 6 months with metronomic chemotherapy, then additional studies would be warranted. RESULTS: The ECOG PS was 0-1 in 92 patients and 2 in 8 patients. The subsite of primary was buccal mucosa in 38 patients (38%), anterior two-third tongue (oral tongue) in 51 patients (51%), and alveolus in 11 patients (11%). The median estimated overall survival was 110 days (95% confidence interval [CI]: 85 134 days). The proportion of patients surviving at 6 months was 26.4% (95% CI: 17.9-35.6). CONCLUSION: Metronomic combination of methotrexate and celecoxib failed to meet its prespecified efficacy limit and should not be used in these patients as routine. PMID- 26855525 TI - Adenoid cystic carcinoma of head and neck: A single institutional analysis of 66 patients treated with multi-modality approach. AB - BACKGROUND: Adenoid cystic carcinoma (ACC) accounts for 1% of all head and neck (HN) cancers. MATERIALS AND METHODS: Demographic, clinical, treatment, and survival details of 66 patients were collected (1995-2011) and analyzed. Disease free survival (DFS) was estimated by Kaplan-Meier method. RESULTS: Primary disease sites were sinonasal (n = 27), salivary gland (n = 30), and others (n = 9). Median follow-up was 23 months (range: 12-211 months). Estimated DFS at 2- and 5-year were 75% and 67.2%, respectively. On univariate analysis, intra cranial extension (ICE) (hazard ratio [HR]: 3.59, P = 0.0071), lymph node involvement (HR: 4.05, P = 0.0065), treatment modality (others vs. surgery plus adjuvant radiotherapy, HR: 2.39, P = 0.0286) and T stage (T3/4 vs. T1/2, HR: 3.27, P = 0.007) had significant impact on DFS. Lymph node involvement (P = 0.038) and ICE (P = 0.038) continued to have significant impact on DFS on multivariate analysis. CONCLUSION: Surgery followed by adjuvant radiotherapy remains the treatment of choice for HN ACC. Lymph node involvement and ICE confer poor prognosis. PMID- 26855526 TI - Neoadjuvant chemotherapy in technically unresectable carcinoma of external auditory canal. AB - BACKGROUND: Carcinoma of external auditory canal (EAC) is a very rare malignancy with surgical resection as the main modality of treatment. The outcomes with nonsurgical modalities are very dismal. We present a retrospective analysis of 4 patients evaluating the role of neoadjuvant chemotherapy in technically unresectable cancers. MATERIALS AND METHODS: This is a retrospective analysis of 4 patients from our institute from 2010 to 2014 with carcinoma EAC who were deemed unfit for surgery due to extensive disease involving occipital bone with soft tissue infiltration (n = 2), temporal dura (n = 1), left temporal lobe, and extensive soft tissue involvement (n = 1). All these patients received neoadjuvant chemotherapy with docetaxel, cisplatin and 5 fluorouracil (n = 3) and paclitaxel and cisplatin (n = 1). RESULTS: Response evaluation showed a partial response (PR) in 3 and stable disease (SD) in 1 patient by Response Evaluation Criteria in Solid Tumors criteria. All 3 patients who received 3 drug chemotherapy had PR while 1 patient who received 2 drug chemotherapy had SD. Two of these patients underwent surgery, and other 2 underwent definitive chemoradiation. One of 3 patients who achieved PR underwent surgical resection; the other 2 remained unresectable in view of the persistent intradural extension and infratemporal fossa involvement. One patient who had SD could undergo surgery in view of clearance of infraatemporal fossa. Recent follow-up shows that 3 out of these 4 patients are alive. CONCLUSION: This indicates that there may be a role of induction chemotherapy in converting potentially unresectable tumors to resectable disease that could produce better outcomes in carcinoma EAC. PMID- 26855527 TI - Clinicopathological pattern of cranial unifocal Langerhans cell histiocytosis: A study at medical college hospital. AB - BACKGROUND: Eosinophilic granuloma (EG) of bone refers to a generally benign form of Langerhans cell histiocytosis localized to the bone. Patients may present with a solitary lesion (monostotic) or multiple sites of involvement (polyostotic). MATERIALS AND METHODS: This study was done to evaluate the clinicopathological pattern of 6 cases of EGs of the skull diagnosed at a tertiary care hospital. All patients of EG were included with the help of medical records over a 5-year period that is, November 2009 to November 2014. They all had been preoperatively evaluated by skull X-ray and computed tomography. To rule out a multifocal disease scintigraphy was performed in all cases preoperatively. Surgical excision was performed, and EG was diagnosed on histopathology and immunohistochemistry. RESULTS: There was a male predominance. Parietal bone was the most common affected bone. Total excision of the lesion was performed in all cases. No patient received postoperative radiotherapy. The follow-up period ranged from 6 months to 3 years. No tumor recurrence was noted. CONCLUSION: With an unknown etiology, nonspecific clinical and radiological findings with diagnosis possible only on histopathological examination, EG needs to be considered in the differential diagnosis as a skull mass, especially in children. PMID- 26855528 TI - Institutional external peer review: A unique National Cancer Grid initiative. PMID- 26855530 TI - Juxtaoral organ of Chievitz: A histopathological masquerade. PMID- 26855529 TI - Breast and gastrointestinal cancer updates from ASCO 2015. AB - This review focuses on the updates presented at the ASCO 2015 symposium in breast and gastrointestinal malignancies. Some were practice changing while others gave us an exciting glimpse into what's to come in the very near future. Immunotherapy was the buzz word this year with data presented on every tumor site. Data on the efficacy of anti PD-1 agents in colorectal, hepatocellular and gastric cancer were presented. In breast cancer we saw data on a new and exciting therapeutic target in the form of androgen receptor among triple receptor negative breast tumors presented. Positive results of the PALOMA 3 trial were presented that has given women with hormone receptor positive metastatic breast cancer another therapeutic option. Furthermore data on strategies to further improve anti her2 therapy, optimizing of chemotherapy in the early and advanced stage and various strategies to improve endocrine therapy among patients with breast cancer were presented. PMID- 26855531 TI - Giant mediastinal carcinoid. PMID- 26855532 TI - Clinical nutrition in the hepatogastroenterology curriculum. AB - Gastroenterology (GE) used to be considered a subspecialty of internal medicine. Today, GE is generally recognized as a wide-ranging specialty incorporating capacities, such as hepatology, oncology and interventional endoscopy, necessitating GE-expert differentiation. Although the European Board of Gastroenterology and Hepatology has defined specific expertise areas in Advanced endoscopy, hepatology, digestive oncology and clinical nutrition, training for the latter topic is lacking in the current hepatogastroenterology (HGE) curriculum. Given its relevance for HGE practice, and being at the core of gastrointestinal functioning, there is an obvious need for training in nutrition and related issues including the treatment of disease-related malnutrition and obesity and its associated metabolic derangements. This document aims to be a starting point for the integration of nutritional expertise in the HGE curriculum, allowing a central role in the management of malnutrition and obesity. We suggest minimum endpoints for nutritional knowledge and expertise in the standard curriculum and recommend a focus period of training in nutrition issues in order to produce well-trained HGE specialists. This article provides a road map for the organization of such a training program. We would highly welcome the World Gastroenterology Organisation, the European Board of Gastroenterology and Hepatology, the American Gastroenterology Association and other (inter)national Gastroenterology societies support the necessary certifications for this item in the HGE-curriculum. PMID- 26855533 TI - Clinical and molecular features of young-onset colorectal cancer. AB - Colorectal cancer (CRC) is one of the leading causes of cancer related mortality worldwide. Although young-onset CRC raises the possibility of a hereditary component, hereditary CRC syndromes only explain a minority of young-onset CRC cases. There is evidence to suggest that young-onset CRC have a different molecular profile than late-onset CRC. While the pathogenesis of young-onset CRC is well characterized in individuals with an inherited CRC syndrome, knowledge regarding the molecular features of sporadic young-onset CRC is limited. Understanding the molecular mechanisms of young-onset CRC can help us tailor specific screening and management strategies. While the incidence of late-onset CRC has been decreasing, mainly attributed to an increase in CRC screening, the incidence of young-onset CRC is increasing. Differences in the molecular biology of these tumors and low suspicion of CRC in young symptomatic individuals, may be possible explanations. Currently there is no evidence that supports that screening of average risk individuals less than 50 years of age will translate into early detection or increased survival. However, increasing understanding of the underlying molecular mechanisms of young-onset CRC could help us tailor specific screening and management strategies. The purpose of this review is to evaluate the current knowledge about young-onset CRC, its clinicopathologic features, and the newly recognized molecular alterations involved in tumor progression. PMID- 26855534 TI - Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances. AB - Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID- 26855535 TI - Advances in endoscopic ultrasound imaging of colorectal diseases. AB - The development of endoscopic ultrasound (EUS) has had a significant impact for patients with digestive diseases, enabling enhanced diagnostic and therapeutic procedures, with most of the available evidence focusing on upper gastrointestinal (GI) and pancreatico-biliary diseases. For the lower GI tract the main application of EUS has been in staging rectal cancer, as a complementary technique to other cross-sectional imaging methods. EUS can provide highly accurate in-depth assessments of tumour infiltration, performing best in the diagnosis of early rectal tumours. In the light of recent developments other EUS applications for colorectal diseases have been also envisaged and are currently under investigation, including beyond-rectum tumour staging by means of the newly developed forward-viewing radial array echoendoscope. Due to its high resolution, EUS might be also regarded as an ideal method for the evaluation of subepithelial lesions. Their differential diagnosis is possible by imaging the originating wall layer and the associated echostructure, and cytological and histological confirmation can be obtained through EUS-guided fine needle aspiration or trucut biopsy. However, reports on the use of EUS in colorectal subepithelial lesions are currently limited. EUS allows detailed examination of perirectal and perianal complications in Crohn's disease and, as a safe and less expensive investigation, can be used to monitor therapeutic response of fistulae, which seems to improve outcomes and reduce the need for additional surgery. Furthermore, EUS image enhancement techniques, such as the use of contrast agents or elastography, have recently been evaluated for colorectal indications as well. Possible applications of contrast enhancement include the assessment of tumour angiogenesis in colorectal cancer, the monitoring of disease activity in inflammatory bowel disease based on quantification of bowel wall vascularization, and differentiating between benign and malignant subepithelial tumours. Recent reports suggest that EUS elastography enables highly accurate discrimination of colorectal adenocarcinomas from adenomas, while inflammatory bowel disease phenotypes can be distinguished based on the strain ratio calculation. Among EUS guided therapies, the drainage of abdominal and pelvic collections has been regarded as a safe and effective procedure to be used as an alternative for the transcutaneous route, while the placing of fiducial markers under EUS guidance for targeted radiotherapy in rectal cancer or the use of contrast microbubbles as drug-delivery vehicles represent experimental therapeutic applications that could greatly impact the forthcoming management of patients with colorectal diseases, pending on further investigations. PMID- 26855536 TI - Seeing better--Evidence based recommendations on optimizing colonoscopy adenoma detection rate. AB - Colorectal cancer is one of the three most frequent causes of cancer deaths in men and women in Europe and North America. Diagnosis and resection of adenomas has convincingly demonstrated its utility in diminishing colorectal cancer incidence. Therefore, colonoscopy is now the gold standard for colorectal cancer screening. But it is also known that colonoscopy effectiveness varies among endoscopists. Among different quality indicators, the most used is the adenoma detection rate (ADR) which is the percentage of average-risk patients for colorectal cancer who are found to have at least one adenoma or adenocarcinoma during a screening colonoscopy. There is compelling evidence supporting an inverse correlation between ADR and interval colorectal cancer (cancer found after a screening colonoscopy). Many factors such as quality of precolonoscopy preparation, additional observers, manoeuvres with the endoscope (second view, retroflexion, water inflation rather than air), time spent during withdrawal, changes in patient position, fold-flattener devices, new imaging or endoscopic modalities and use of intravenous or through the scope sprayed drugs, have been studied and developed with the aim of increasing the ADR. This reviews discusses these factors, and the current evidence, to "see better" in the colon and optimize ADR. PMID- 26855537 TI - Endoscopic ultrasonography: Transition towards the future of gastro-intestinal diseases. AB - Endoscopic ultrasonography (EUS) is a technique with an established role in the diagnosis and staging of gastro-intestinal tumors. In recent years, the spread of new devices dedicated to tissue sampling has improved the diagnostic accuracy of EUS fine-needle aspiration. The development of EUS-guided drainage of the bilio pancreatic region and abdominal fluid collections has allowed EUS to evolve into an interventional tool that can replace more invasive procedures. Emerging techniques applying EUS in pancreatic cancer treatment and in celiac neurolysis have been described. Recently, confocal laser endomicroscopy has been applied to EUS as a promising technique for the in vivo histological diagnosis of gastro intestinal, bilio-pancreatic and lymph node lesions. In this state-of-the-art review, we report the most recent data from the literature regarding EUS devices, interventional EUS, EUS-guided confocal laser endomicroscopy and EUS pancreatic cancer treatment, and we also provide an overview of their principles, clinical applications and limitations. PMID- 26855538 TI - MicroRNA aberrations: An emerging field for gallbladder cancer management. AB - Gallbladder cancer (GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment options. These necessitate development of early prognostic/predictive markers and novel therapeutic interventions. MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a key role in tumor biology by functioning like tumor suppressor- or onco- genes and their aberrant expression are associated with the pathogenesis of several neoplasms with overwhelming clinical implications. Since miRNA signature is tissue specific, here, we focused on current data concerning the miRNAs aberrations in GBC pathogenesis. In GBC, miRNAs with tumor suppressor activity (miR-135-5p, miR-335, miR-34a, miR-26a, miR-146b-5p, Mir-218-5p, miR-1, miR-145, mir-130a) were found downregulated, while those with oncogenic property (miR-20a, miR-182, mir-155) were upregulated. The expression profile of miRNAs was significantly associated with GBC prognosis and prediction, and forced over expression/ inhibition of these miRNAs was shown to affect tumor growth and development. Further, differential expression of miRNAs in the blood samples of GBC patients suggest miRNAs as promising noninvasive biomarker. Thus, miRNAs represent potential candidate for GBC management, though many hurdles need to be overcome before miRNAs therapy can be clinically applied to GBC prevention and treatment. PMID- 26855539 TI - Gender difference in gastro-esophageal reflux diseases. AB - The incidence of esophageal adenocarcinoma (EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease (GERD) to Barrett's esophagus (BE, a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have described that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen. PMID- 26855540 TI - Application of robotics in gastrointestinal endoscopy: A review. AB - Multiple robotic flexible endoscope platforms have been developed based on cross specialty collaboration between engineers and medical doctors. However, significant number of these platforms have been developed for the natural orifice transluminal endoscopic surgery paradigm. Increasing amount of evidence suggest the focus of development should be placed on advanced endolumenal procedures such as endoscopic submucosal dissection instead. A thorough literature analysis was performed to assess the current status of robotic flexible endoscopic platforms designed for advanced endolumenal procedures. Current efforts are mainly focused on robotic locomotion and robotic instrument control. In the future, advances in actuation and servoing technology, optical analysis, augmented reality and wireless power transmission technology will no doubt further advance the field of robotic endoscopy. Globally, health systems have become increasingly budget conscious; widespread acceptance of robotic endoscopy will depend on careful design to ensure its delivery of a cost effective service. PMID- 26855541 TI - Chymase inhibitor TY-51469 in therapy of inflammatory bowel disease. AB - AIM: To investigate the effect of chymase inhibitor TY-51469 in the therapy of inflammatory bowel disease and the underlying mechanism. METHODS: Seventy-five healthy Sprague-Dawley rats were randomly assigned to one of the three groups (control group, model group and TY-51469 experiment group) and each group had twenty-five rats. The rats of the model group and experiment group were subjected to treatment with 3.5% dextran sulfate sodium (DSS) 10 mg/kg to induce colitis. The control group and model group were subjected to intraperitoneal injection of saline, while the experiment group was subjected to intraperitoneal injection of 10 mg/kg TY-51469 each day. Five rats of each group were sacrificed on 0, 7, 14, 21 and 28 d, respectively. The degree of inflammation was assessed by histopathological scoring; flow cytometry was performed to detect the proportion of CD4(+)CD25(+) Tregs in peripheral blood; colon tissues of rats were collected to measure mRNA and protein expression by PCR, Western blot and immunohistochemistry; serum levels of interleukin (IL)-10, transforming growth factor (TGF)-beta1 and IL-17A were detected by ELISA. RESULTS: The rats in the experiment group and model group had significantly more severe colitis than the ones in the control group (P < 0.05) before treatment on day 0; no significant difference was observed between the experiment group and model group (P > 0.05). After treatment with TY-51469, the rats in the experiment group had significantly less severe colitis compared with the model group on 7, 14, 21 and 28 d (P < 0.05). The proportion of CD4(+)CD25(+) Tregs was lower in the model group and experiment group than in the control group; the experiment group had a significantly higher proportion of CD4(+)CD25(+) Tregs than that in the model group (P < 0.05). The model group and experiment group demonstrated lower expression of Foxp3 than the control group; the experiment group had higher Foxp3 expression than the model group (P < 0.05). Cytokines IL-10, TGF-beta1 and IL-17A were lower in the model group and experiment group than in the control group; the experiment group had higher expression than the model group (P < 0.05). CONCLUSION: After treatment with chymase inhibitor TY-51469, the experiment group demonstrated more significantly reduced intestinal inflammation and higher expression of immune tolerance related cytokines (IL-10, TGF-beta1, IL-17A) and Foxp3 which is specifically expressed in Tregs compared with the model group. Therefore, chymase inhibitor TY-51469 might ameliorate the progression of DSS induced colitis possibly by increasing the expression of Tregs and cytokines. PMID- 26855542 TI - Electroacupuncture at ST25 inhibits jejunal motility: Role of sympathetic pathways and TRPV1. AB - AIM: To investigate whether electroacupuncture (EA) at ST25 affects jejunal motility in vivo and if so, whether a sympathetic pathway is involved. METHODS: Jejunal motility was assessed using a manometric balloon placed in the jejunum approximately about 3-5 cm away from the suspensory ligament of the duodenum in anesthetized animals. The effects of EA at ST25 were measured in male Sprague Dawley rats, some of which were treated with propranolol or clenbuterol (EA intensities: 1, 3, 5, 7, and 9 mA), and in male transient receptor potential vanilloid-1 (TRPV1) (capsaicin receptor) knockout mice (EA intensities: 1, 2, and 4 mA). RESULTS: Anesthetized rats exhibited three types of fasting jejunal motor patterns (types A, B, and C), and only type C rats responded to EA stimulation. In type C rats, EA at ST25 significantly suppressed the motor activity of the jejunum in an intensity-dependent manner. The inhibitory effect of EA was weakened by propranolol (beta adrenoceptor antagonist) and disappeared with clenbuterol (beta adrenoceptor agonist) induced inhibition of motility, suggesting that the effect of EA on motility is mediated via a sympathetic pathway. Compared with wild-type mice, EA at ST25 was less effective in TRPV1 knockout mice, suggesting that this multi-modal sensor channel participates in the mechanism. CONCLUSION: EA at ST25 was found to inhibit jejunal motility in an intensity-dependent manner, via a mechanism in which sympathetic nerves and TRPV1 receptors play an important role. PMID- 26855543 TI - One hundred and one over-the-scope-clip applications for severe gastrointestinal bleeding, leaks and fistulas. AB - AIM: To investigate the efficacy and clinical outcome of patients treated with an over-the-scope-clip (OTSC) system for severe gastrointestinal hemorrhage, perforations and fistulas. METHODS: From 02-2009 to 10-2012, 84 patients were treated with 101 OTSC clips. 41 patients (48.8%) presented with severe upper gastrointestinal (GI) bleeding, 3 (3.6%) patients with lower-GI bleeding, 7 patients (8.3%) underwent perforation closure, 18 patients (21.4%) had prevention of secondary perforation, 12 patients (14.3%) had control of secondary bleeding after endoscopic mucosal resection or endoscopic submucosal dissection (ESD) and 3 patients (3.6%) had an intervention on a chronic fistula. RESULTS: In 78/84 patients (92.8%), primary treatment with the OTSC was technically successful. Clinical primary success was achieved in 75/84 patients (89.28%). The overall mortality in the study patients was 11/84 (13.1%) and was seen in patients with life-threatening upper GI hemorrhage. There was no mortality in any other treatment group. In detail OTSC application lead to a clinical success in 35/41 (85.36%) patients with upper GI bleeding and in 3/3 patients with lower GI bleeding. Technical success of perforation closure was 100% while clinical success was seen in 4/7 cases (57.14%) due to attendant circumstances unrelated to the OTSC. Technical and clinic success was achieved in 18/18 (100%) patients for the prevention of bleeding or perforation after endoscopic mucosal resection and ESD and in 3/3 cases of fistula closure. Two application-related complications were seen (2%). CONCLUSION: This largest single center experience published so far confirms the value of the OTSC for GI emergencies and complications. Further clinical experience will help to identify optimal indications for its targeted and prophylactic use. PMID- 26855544 TI - Nutritional status of children with inflammatory bowel disease in Saudi Arabia. AB - AIM: To assess the prevalence of nutritional disorders in children with inflammatory bowel disease (IBD) in Saudi Arabia. METHODS: The data from a national cohort of children newly diagnosed with IBD between 2003 and 2012 were analyzed. The diagnosis of IBD and the differentiation between Crohn's disease (CD) and ulcerative colitis (UC) were confirmed by gastroenterologists according to the standard criteria. The body mass index (BMI) of each child [weight (kg)/height(2) (m)] was calculated at the time of diagnosis. The World Health Organization standards and references were used and the BMI for age > +1 and < -2 standard deviation score were used to define overweight and thinness, respectively. Age stratification analysis was performed to investigate any age related variation in the prevalence of nutritional status between children < 10 years of age and older. RESULTS: There were 374 children from 0.33 to 17 years of age, including 119 (32%) children with UC and 255 (68%) with CD. All of the children were Saudi nationals, and 68 (57%) of the UC and 150 (59%) of the CD children were males. A positive history of anorexia at the time of diagnosis was found in 30 (25%) patients with UC and 99 (39%) patients with CD. The prevalence of thinness was 31%, 35% and 24% in children with IBD, CD and UC, respectively, with a significantly higher prevalence of thinness in children with CD than in children with UC (P = 0.037) only in the age group of 10-17 years (P = 0.030). The prevalence of overweight was 16 %, 15% and 20 % in the children with IBD, CD and UC, respectively, indicating a higher prevalence in UC that was statistically significant only in the age group of 10-17 years (P = 0.020). CONCLUSION: A high proportion of children with IBD presented with overweight instead of the classical underweight. Awareness of this finding is important for patient care. PMID- 26855545 TI - Staging laparoscopy improves treatment decision-making for advanced gastric cancer. AB - AIM: To evaluate the clinical value of staging laparoscopy in treatment decision making for advanced gastric cancer (GC). METHODS: Clinical data of 582 patients with advanced GC were retrospectively analyzed. All patients underwent staging laparoscopy. The strength of agreement between computed tomography (CT) stage, endoscopic ultrasound (EUS) stage, laparoscopic stage, and final stage were determined by weighted Kappa statistic (Kw). The number of patients with treatment decision-changes was counted. A chi(2) test was used to analyze the correlation between peritoneal metastasis or positive cytology and clinical characteristics. RESULTS: Among the 582 patients, the distributions of pathological T classifications were T2/3 (153, 26.3%), T4a (262, 45.0%), and T4b (167, 28.7%). Treatment plans for 211 (36.3%) patients were changed after staging laparoscopy was performed. Two (10.5%) of 19 patients in M1 regained the opportunity for potential radical resection by staging laparoscopy. Unnecessary laparotomy was avoided in 71 (12.2%) patients. The strength of agreement between preoperative T stage and final T stage was in almost perfect agreement (Kw = 0.838; 95% confidence interval (CI): 0.803-0.872; P < 0.05) for staging laparoscopy; compared with CT and EUS, which was in fair agreement. The strength of agreement between preoperative M stage and final M stage was in almost perfect agreement (Kw = 0.990; 95% CI: 0.977-1.000; P < 0.05) for staging laparoscopy; compared with CT, which was in slight agreement. Multivariate analysis revealed that tumor size (>= 40 mm), depth of tumor invasion (T4b), and Borrmann type (III or IV) were significantly correlated with either peritoneal metastasis or positive cytology. The best performance in diagnosing P-positive was obtained when two or three risk factors existed. CONCLUSION: Staging laparoscopy can improve treatment decision-making for advanced GC and decrease unnecessary exploratory laparotomy. PMID- 26855546 TI - Diagnostic value of high-resolution micro-endoscopy for the classification of colon polyps. AB - AIM: To study a new imaging equipment, high-resolution micro-endoscopy (HRME), in the diagnosis and pathological classification of colon polyps. METHODS: We selected 114 specimens of colon polyps, 30 of which were colon polyps with known pathological types and 84 that were prospective polyp specimens; 10 normal colon mucosa specimens served as controls. We obtained images of 30 colon polyp specimens with known pathological types using HRME and analyzed the characteristics of these images to develop HRME diagnostic criteria for different pathological types of colon polyps. Based on these criteria, we performed a prospective study of 84 colon polyp specimens using HRME and compared the results with those of the pathological examination to evaluate the diagnostic value of HRME in the pathological classification of different types of colon polyps. RESULTS: In the 30 cases of known pathological type of colon polyp samples, there were 21 cases of adenomatous polyps, which comprised nine cases of tubular adenoma, seven cases of villous adenoma and five cases of mixed adenomas. The nine cases of non-adenomatous polyps included four cases of inflammatory polyps and five cases of hyperplastic polyps five. Ten cases of normal colonic mucosa were confirmed pathologically. In a prospective study of 84 cases using HRME, 23 cases were diagnosed as inflammatory polyps, 11 cases as hyperplastic polyps, 18 cases as tubular adenoma, eight cases as villous adenoma and 24 cases as mixed adenomas. After pathological examination, 24 cases were diagnosed as inflammatory polyps, 11 cases as hyperplastic polyps, 19 cases as tubular adenoma, eight cases as villous adenoma and 22 cases as mixed adenomas. Compared with the pathological examinations, the sensitivities, specificities, accuracies, and positive and negative predictive values of HRME in diagnosing inflammatory polyps (87.5%, 96.7%, 94.0%, 91.3% and 95.1%), hyperplastic polyps (72.7%, 95.9%, 92.9%, 72.7% and 95.9%), tubular adenomas (73.7%, 93.8%, 89.3%, 77.8% and 92.4%), villous adenomas (75.0%, 97.4%, 95.2%, 75.0% and 97.4%), and mixed adenomas (75.0%, 93.3%, 88.1%, 81.8% and 90.3%) were relatively high. CONCLUSION: HRME has a relatively high diagnostic value in the pathological classification of colon polyps. Thus, it may be an alternative to confocal microendoscopy in lower resource or community-based settings. PMID- 26855547 TI - Italian survey on non-steroidal anti-inflammatory drugs and gastrointestinal bleeding in children. AB - AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug (NSAIDs) use in children. METHODS: A retrospective, multicenter study was conducted between January 2005 and January 2013, with the participation of 8 Italian pediatric gastroenterology centers. We collected all the cases of patients who refer to emergency room for suspected gastrointestinal bleeding following NSAIDs consumption, and underwent endoscopic evaluation. Previous medical history, associated risk factors, symptoms and signs at presentation, diagnostic procedures, severity of bleeding and management of gastrointestinal bleeding were collected. In addition, data regarding type of drug used, indication, dose, duration of treatment and prescriber (physician or self-medication) were examined. RESULTS: Fifty-one patients, including 34 males, were enrolled (median age: 7.8 years). Ibuprofen was the most used NSAID [35/51 patients (68.6%)]. Pain was the most frequent indication for NSAIDs use [29/51 patients (56.9%)]. Seven patients had positive family history of Helicobacter pylori (H. pylori) infection or peptic ulcer, and 12 had associated comorbidities. Twenty-four (47%) out of 51 patients used medication inappropriately. Hematemesis was the most frequent symptom (33.3%). Upper gastrointestinal endoscopy revealed gastric lesions in 32/51 (62%) patients, duodenal lesions in 17 (33%) and esophageal lesions in 8 (15%). In 10/51 (19.6%) patients, a diagnosis of H. pylori gastritis was made. Forty-eight (94%) patients underwent medical therapy, with spontaneous bleeding resolution, while in 3/51 (6%) patients, an endoscopic hemostasis was needed. CONCLUSION: The data collected in this study confirms that adverse events with the involvement of the gastrointestinal tract secondary to NSAID use are also common in children. PMID- 26855548 TI - Association between serum alpha-L-fucosidase and non-alcoholic fatty liver disease: Cross-sectional study. AB - AIM: To explore the association between serum alpha-L-fucosidase (AFU) and non alcoholic fatty liver disease (NAFLD). METHODS: A total of 16473 individuals (9456 men and 7017 women) were included in the current study, who presented for a health examination at the First Affiliated Hospital of Zhejiang University School of Medicine in 2014. The baseline characteristics of the cohort were compared by NAFLD status. Linear regression analysis and stepwise multiple regression analysis were applied to assess the risk factors for NAFLD. Receiver operating characteristic curve was used to determine the sensitivity and specificity of AFU in the diagnosis of NAFLD. RESULTS: The prevalence rates of NAFLD and metabolic syndrome (MetS) were 38.0% and 25.4%, respectively. The NAFLD group had significantly higher AFU levels than the non-NAFLD group (28.7 +/- 7.9 U/L vs 26.0 +/- 7.3 U/L, P < 0.001) and the prevalence rate of NAFLD increased with progressively higher serum AFU levels. AFU was positively correlated with MetS and its five components: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and elevated blood pressure and fasting glucose. Stepwise multiple logistic regression analysis showed that AFU was associated with an increased risk of NAFLD (OR = 1.009, 95%CI: 1.003-1.014, P < 0.001). The best cut-off value of AFU for the diagnosis of NAFLD was 27.5 U/L. The area under the curve (diagnostic efficacy index) was 0.606. The sensitivity and specificity were 54.6% and 61.8%, respectively. CONCLUSION: AFU level is significantly associated with NAFLD, and elevated AFU level is an independent risk factor for NAFLD. PMID- 26855549 TI - Diagnostic and therapeutic single-operator cholangiopancreatoscopy in biliopancreatic diseases: Prospective multicenter study in Japan. AB - AIM: To assess the utility and safety of single-operator cholangiopancreatoscopy (SOCPS) using the SpyGlass system in widespread clinical application for biliary and pancreatic diseases. METHODS: This study was a prospective case series conducted in 20 referral centers in Japan. There were 148 patients who underwent SOCPS; 124 for biliary diseases and 24 for pancreatic diseases. The attempted interventions were SOCPS examination, SOCPS-directed tissue sampling, and therapy for stone removal, among others. The main outcomes were related to the procedure success rate in terms of visualizing the target lesions, SOCPS-directed adequate tissue sampling, and complete stone removal. RESULTS: A total of 148 patients were enrolled for the diagnosis of indeterminate biliary and pancreatic lesions or treatment of biliary and pancreatic disease. The overall procedure success rate of visualizing the target lesions was 91.2% (135/148). The overall procedural success rates of visualizing the target lesions of diagnostic SOCPS in the bile duct and pancreatic duct were 95.5% (84/89) and 88.2% (15/17), respectively. DIAGNOSIS: the overall adequate tissue for histologic examination was secured in 81.4% of the 86 patients who underwent biopsy under SOCPS (bile duct, 60/75, 80.0%; pancreatic duct, 10/11, 90.9%). The accuracy of histologic diagnosis using SOCPS-directed biopsies in indeterminate bile duct lesions was 70.7% (53/75). In the pancreatic duct, the accuracy of SOCPS visual impression of intraductal papillary mucinous neoplasm was 87.5% (14/16). Stone therapy: complete biliary and pancreatic stone clearance combined with SOCPS-directed stone therapy using electrohydraulic lithotripsy or laser lithotripsy was achieved in 74.2% (23/31) and 42.9% (3/7) of the patients, respectively. Others: SOCPS using the SpyGlass system was used in cannulation of the cystic duct in two patients and for passing across the obstructed self-expandable metallic stent for a malignant biliary stricture in two patients. All procedures were successful in both SOCPS-guided therapies. The incidence of procedure-related adverse events was 5.4% (8/148). CONCLUSION: SOCPS with direct visualization and biopsy for diagnosis and SOCPS-directed therapy for biliary and pancreatic diseases can be safely performed with a high success rate. The clinical trial was registered at UMIN CTR (http://www.umin.ac.jp). The registration identification number is UMIN000015155. PMID- 26855550 TI - Effectiveness and safety of continuous wound infiltration for postoperative pain management after open gastrectomy. AB - AIM: To prospectively evaluate the effectiveness and safety of continuous wound infiltration (CWI) for pain management after open gastrectomy. METHODS: Seventy five adult patients with American Society of Anesthesiologists (ASA) Physical Status Classification System (ASA) grade 1-3 undergoing open gastrectomy were randomized to three groups. Group 1 patients received CWI with 0.3% ropivacaine (group CWI). Group 2 patients received 0.5 mg/mL morphine intravenously by a patient-controlled analgesia pump (PCIA) (group PCIA). Group 3 patients received epidural analgesia (EA) with 0.12% ropivacaine and 20 ug/mL morphine with an infusion at 6-8 mL/h for 48 h (group EA). A standard general anesthetic technique was used for all three groups. Rescue analgesia (2 mg bolus of morphine, intravenous) was given when the visual analogue scale (VAS) score was >= 4. The outcomes measured over 48 h after the operation were VAS scores both at rest and during mobilization, total morphine consumption, relative side effects, and basic vital signs. Further results including time to extubation, recovery of bowel function, surgical wound healing, mean length of hospitalization after surgery, and the patient's satisfaction were also recorded. RESULTS: All three groups had similar VAS scores during the first 48 h after surgery. Group CWI and group EA, compared with group PCIA, had lower morphine consumption (P < 0.001), less postoperative nausea and vomiting (1.20 +/- 0.41 vs 1.96 +/- 0.67, 1.32 +/- 0.56 vs 1.96 +/- 0.67, respectively, P < 0.001), earlier extubation (16.56 +/- 5.24 min vs 19.76 +/- 5.75 min, P < 0.05, 15.48 +/- 4.59 min vs 19.76 +/- 5.75 min, P < 0.01), and earlier recovery of bowel function (2.96 +/- 1.17 d vs 3.60 +/- 1.04 d, 2.80 +/- 1.38 d vs 3.60 +/- 1.04 d, respectively, P < 0.05). The mean length of hospitalization after surgery was reduced in groups CWI (8.20 +/- 2.58 d vs 10.08 +/- 3.15 d, P < 0.05) and EA (7.96 +/- 2.30 d vs 10.08 +/- 3.15 d, P < 0.01) compared with group PCIA. All three groups had similar patient satisfaction and wound healing, but group PCIA was prone to higher sedation scores when compared with groups CWI and EA, especially during the first 12 h after surgery. Group EA had a lower mean arterial pressure within the first postoperative 12 h compared with the other two groups. CONCLUSION: CWI with ropivacaine yields a satisfactory analgesic effect within the first 48 h after open gastrectomy, with lower morphine consumption and accelerated recovery. PMID- 26855551 TI - Glutathione S-transferase M1 polymorphism and esophageal cancer risk: An updated meta-analysis based on 37 studies. AB - AIM: To evaluate the relationship between glutathione S-transferase M1 (GSTM1) polymorphism and susceptibility to esophageal cancer (EC). METHODS: A comprehensive search of the United States National Library of Medicine PubMed database and the Elsevier, Springer, and China National Knowledge Infrastructure databases for all relevant studies was conducted using combinations of the following terms: "glutathione S-transferase M1", "GSTM1", "polymorphism", and "EC" (until November 1, 2014). The statistical analysis was performed using the SAS software (v.9.1.3; SAS Institute, Cary, NC, United States) and the Review Manager software (v.5.0; Oxford, England); crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between the GSTM1 null genotype and the risk of EC. RESULTS: A total of 37 studies involving 2236 EC cases and 3243 controls were included in this meta-analysis. We observed that the GSTM1 null genotype was a significant risk factor for EC in most populations (OR = 1.33, 95%CI: 1.12-1.57, P heterogeneity < 0.000001, and I (2) = 77.0%), particularly in the Asian population (OR = 1.53, 95%CI: 1.26-1.86, P heterogeneity < 0.000001, and I (2) = 77.0%), but not in the Caucasian population (OR = 1.02, 95%CI: 0.87-1.19, P heterogeneity = 0.97, and I (2) = 0%). CONCLUSION: The GSTM1 null polymorphism may be associated with an increased risk for EC in Asian but not Caucasian populations. PMID- 26855552 TI - Auxiliary partial liver transplantation for acute liver failure using "high risk" grafts: Case report. AB - Acute liver failure (ALF) is a reversible disorder that is associated with an abrupt loss of hepatic mass, rapidly progressive encephalopathy and devastating complications. Despite its high mortality, an emergency liver transplantation nowadays forms an integral part in ALF management and has substantially improved the outcomes of ALF. Here, we report the case of a 32-year-old female patient who was admitted with grade IV hepatic encephalopathy (coma) following drug-induced ALF. We performed an emergency auxiliary partial orthotopic liver transplantation with a "high risk" graft (liver macrovesicular steatosis approximately 40%) from a living donor. The patient was discharged on postoperative day 57 with normal liver function. Weaning from immunosuppression was achieved 9 mo after transplantation. A follow-up using CT scan showed a remarkable increase in native liver volume and gradual loss of the graft. More than 6 years after the transplantation, the female now has a 4-year-old child and has returned to work full-time without any neurological sequelae. PMID- 26855553 TI - WHAT DNA CAN AND CANNOT SAY: PERSPECTIVES OF IMMIGRANT FAMILIES ABOUT THE USE OF GENETIC TESTING IN IMMIGRATION. AB - Genetic technologies are being implemented in areas that extend beyond the field of medicine to address social and legal problems. An emerging example is the implementation of genetic testing in the family petitioning process in immigration policy. This use of genetic testing offers the potential benefits of reducing immigration fraud and making the process more efficient and accessible for immigrants, especially those without documentation. However, little is known about the positive or negative impacts of such testing on immigrant families and their communities. This study collected empirical data through family interviews to understand the experiences and attitudes of individuals who have taken a DNA test to prove a family relationship for immigration purposes. Based on study results, we present a set of recommendations to improve the processes with which DNA testing is applied to immigration cases. We argue that DNA testing might serve as a useful tool for families who lack documentary evidence of a family relationship. However, testing might also reveal sensitive information, such as misattributed parentage, that can damage relationships and cause serious harm to beneficiaries, especially children. Petitioners should be provided with adequate information to form an understanding of the DNA test and its implementation as well as the positive and negative consequences from using it, in order to carefully assess whether DNA testing will help their case. We recommend that additional protections be put in place to safeguard children from the potential impacts of misattributed parentage or disclosure of hidden social adoptions. This research provides empirical evidence to inform policy related to the use of genetic testing in immigration. PMID- 26855555 TI - MBus: An Ultra-Low Power Interconnect Bus for Next Generation Nanopower Systems. AB - As we show in this paper, I/O has become the limiting factor in scaling down size and power toward the goal of invisible computing. Achieving this goal will require composing optimized and specialized-yet reusable-components with an interconnect that permits tiny, ultra-low power systems. In contrast to today's interconnects which are limited by power-hungry pull-ups or high-overhead chip select lines, our approach provides a superset of common bus features but at lower power, with fixed area and pin count, using fully synthesizable logic, and with surprisingly low protocol overhead. We present MBus, a new 4-pin, 22.6 pJ/bit/chip chip-to-chip interconnect made of two "shoot-through" rings. MBus facilitates ultra-low power system operation by implementing automatic power gating of each chip in the system, easing the integration of active, inactive, and activating circuits on a single die. In addition, we introduce a new bus primitive: power oblivious communication, which guarantees message reception regardless of the recipient's power state when a message is sent. This disentangles power management from communication, greatly simplifying the creation of viable, modular, and heterogeneous systems that operate on the order of nanowatts. To evaluate the viability, power, performance, overhead, and scalability of our design, we build both hardware and software implementations of MBus and show its seamless operation across two FPGAs and twelve custom chips from three different semiconductor processes. A three-chip, 2.2 mm3 MBus system draws 8 nW of total system standby power and uses only 22.6 pJ/bit/chip for communication. This is the lowest power for any system bus with MBus's feature set. PMID- 26855556 TI - On 'Organized Crime' in the illicit antiquities trade: moving beyond the definitional debate. AB - The extent to which 'organized crime' is involved in illicit antiquities trafficking is unknown and frequently debated. This paper explores the significance and scale of the illicit antiquities trade as a unique transnational criminal phenomenon that is often said to be perpetrated by and exhibit traits of so-called 'organized crime.' The definitional debate behind the term 'organized crime' is considered as a potential problem impeding our understanding of its existence or extent in illicit antiquities trafficking, and a basic progression based model is then suggested as a new tool to move beyond the definitional debate for future research that may help to elucidate the actors, processes and criminal dynamics taking place within the illicit antiquities trade from source to market. The paper concludes that researchers should focus not on the question of whether organized criminals- particularly in a traditionally conceived, mafia type stereotypical sense- are involved in the illicit antiquities trade, but instead on the structure and progression of antiquities trafficking itself that embody both organized and criminal dynamics. PMID- 26855554 TI - Evidence-Based Reading and Writing Assessment for Dyslexia in Adolescents and Young Adults. AB - The same working memory and reading and writing achievement phenotypes (behavioral markers of genetic variants) validated in prior research with younger children and older adults in a multi-generational family genetics study of dyslexia were used to study 81 adolescent and young adults (ages 16 to 25) from that study. Dyslexia is impaired word reading and spelling skills below the population mean and ability to use oral language to express thinking. These working memory predictor measures were given and used to predict reading and writing achievement: Coding (storing and processing) heard and spoken words (phonological coding), read and written words (orthographic coding), base words and affixes (morphological coding), and accumulating words over time (syntax coding); Cross-Code Integration (phonological loop for linking phonological name and orthographic letter codes and orthographic loop for linking orthographic letter codes and finger sequencing codes), and Supervisory Attention (focused and switching attention and self-monitoring during written word finding). Multiple regressions showed that most predictors explained individual difference in at least one reading or writing outcome, but which predictors explained unique variance beyond shared variance depended on outcome. ANOVAs confirmed that research-supported criteria for dyslexia validated for younger children and their parents could be used to diagnose which adolescents and young adults did (n=31) or did not (n=50) meet research criteria for dyslexia. Findings are discussed in reference to the heterogeneity of phenotypes (behavioral markers of genetic variables) and their application to assessment for accommodations and ongoing instruction for adolescents and young adults with dyslexia. PMID- 26855557 TI - A Silicon SPECT System for Molecular Imaging of the Mouse Brain. AB - We previously demonstrated the feasibility of using silicon double-sided strip detectors (DSSDs) for SPECT imaging of the activity distribution of iodine-125 using a 300-micrometer thick detector. Based on this experience, we now have developed fully customized silicon DSSDs and associated readout electronics with the intent of developing a multi-pinhole SPECT system. Each DSSD has a 60.4 mm * 60.4 mm active area and is 1 mm thick. The strip pitch is 59 micrometers, and the readout of the 1024 strips on each side gives rise to a detector with over one million pixels. Combining four high-resolution DSSDs into a SPECT system offers an unprecedented space-bandwidth product for the imaging of single-photon emitters. The system consists of two camera heads with two silicon detectors stacked one behind the other in each head. The collimator has a focused pinhole system with cylindrical-shaped pinholes that are laser-drilled in a 250 MUm tungsten plate. The unique ability to collect projection data at two magnifications simultaneously allows for multiplexed data at high resolution to be combined with lower magnification data with little or no multiplexing. With the current multi-pinhole collimator design, our SPECT system will be capable of offering high spatial resolution, sensitivity and angular sampling for small field-of-view applications, such as molecular imaging of the mouse brain. PMID- 26855558 TI - Value of optical coherence tomography in the detection of macular pathology before the removal of silicone oil. AB - PURPOSE: To assess the pathological macular changes with optical coherence tomography (OCT) before the removal of silicone oil (SiO) in eyes that had undergone pars plana vitrectomy for complicated forms of retinal detachment (RD). PATIENTS AND METHODS: Subjects included 48 patients (51 eyes) with complicated RD including proliferative vitreoretinopathy, proliferative diabetic retinopathy, recurrent RD, penetrating trauma, uveitis, giant retinal tears, and macular holes. All the eyes had undergone SiO injection. Furthermore, all eyes had been planned for the removal of SiO 6-12 months after the primary surgery. Finally, all eyes had a fundus examination and OCT examination before the silicone oil removal. RESULTS: OCT findings indicated epiretinal membrane in 41% of the eyes, macular edema in 17%, macular detachment in 13.5%, macular thinning in 13.5%, macular holes in 10%, and subretinal membranes in 2%. Preoperative OCT was normal in only 12% of the eyes, while a clinical fundus examination was normal in 43% (P<0.001). Eyes with normal OCT had significantly better mean logMAR (0.35) than eyes with pathological changes detected through OCT (1.28; P<0.001). Surgical modifications were made during the removal of SiO in 74.5% of the eyes. CONCLUSION: OCT detected significantly more pathological changes than a clinical fundus examination. This had an impact on both surgical step modification during the removal of SiO and predictability of visual outcome after the removal of SiO. PMID- 26855559 TI - Astigmatism management in cataract surgery with Precizon((r)) toric intraocular lens: a prospective study. AB - PURPOSE: The purpose of this study was to evaluate the visual and refractive outcomes and rotational stability of the new aspheric Precizon((r)) toric intraocular lens (IOL) for the correction of corneal astigmatism in cataract surgery. SETTING: Department of Ophthalmology, Hospital Geral de Santo Antonio - Centro Hospitalar do Porto, EPE and Hospital de Pedro Hispano, Matosinhos, Portugal. DESIGN: This was a prospective clinical study. PATIENTS AND METHODS: A total of 40 eyes of 27 patients with corneal astigmatism greater than 1.0 diopter (D) underwent cataract surgery with implantation of Precizon((r)) toric IOL. IOL power calculation was performed using optical coherence biometry (IOLMaster((r))). Outcomes of uncorrected (UDVA) and best-spectacle corrected distance visual acuities (BCDVA), refraction, and IOL rotation were analyzed at the 1st week, 1st, 3rd, and 6th month's evaluations. RESULTS: The median postoperative UDVA was better than preoperative best-spectacle corrected distance visual acuity (0.02 [0.06] logMAR vs 0.19 [0.20] logMAR, P<0.001). At 6 months, postoperative UDVA was 0.1 logMAR or better in 95% of the eyes. At last follow up, the mean spherical equivalent was reduced from -3.35+/-3.10 D to -0.02+/-0.30 D (P<0.001) with 97.5% of the eyes within +/-0.50 D of emmetropia. The mean preoperative keratometric cylinder was 2.34+/-0.95 D and the mean postoperative refractive cylinder was 0.24+/-0.27 D (P<0.001). The mean IOL rotation was 2.43 degrees +/-1.55 degrees . None of the IOLs required realignment. CONCLUSION: Precizon((r)) toric IOL revealed very good rotational stability and performance regarding predictability, efficacy, and safety in the correction of preexisting regular corneal astigmatism associated with cataract surgery. PMID- 26855560 TI - Lysyl oxidase-like 1 polymorphisms in a southwestern Greek cataract population with pseudoexfoliation syndrome. AB - PURPOSE: The aim of this study was to determine the possible association of rs1048661 and rs3825942 single nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene of cataract patients from southwestern Greece with pseudoexfoliation (PEX) syndrome. PATIENTS AND METHODS: Ninety-three patients with PEX syndrome and 74 without PEX syndrome were recruited with the principal diagnosis being cataract. LOXL1 SNPs, rs1048661 and rs3825942, were genotyped by using polymerase chain reaction. RESULTS: The G allele of rs1048661 was found in 96.7% in the PEX group as compared to 80.5% of non-PEX alleles (P=19*10(-4); Odds ratio [OR] =5.37; 95% confidence interval [CI] =1.68-17.12). Similarly, the G allele of rs3825942 was found in 72.1% of the PEX group as compared to 41.8% of non-PEX alleles (P=4*10(-5); OR =3.78; 95% CI =1.98-7.23). The T and A allele frequencies of rs1048661 and rs3825942, respectively, were underrepresented in the PEX group patients as compared to non-PEX group. CONCLUSION: Our data confirm previously reported association between LOXL1 polymorphisms and PEX syndrome in a southwestern Greek population. A significant association was found for the G allele of rs1048661 and rs3825942 demonstrating that the GG haplotype is a high risk factor for the development of PEX syndrome. PMID- 26855561 TI - Effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in healthy Chinese volunteers. AB - PURPOSE: To investigate the effects of probenecid and cimetidine on the pharmacokinetics of nemonoxacin in humans. METHODS: Two independent, open-label, randomized, crossover studies were conducted in 24 (12 per study) healthy Chinese volunteers. In Study 1, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with 1.5 g of probenecid divided into three doses within 25 hours. In Study 2, each volunteer received a single oral dose of 500 mg of nemonoxacin alone or with multiple doses of cimetidine (400 mg thrice daily for 7 days). The plasma and urine nemonoxacin concentrations were determined using validated liquid chromatography-tandem mass spectrometry methods. RESULTS: Coadministration of nemonoxacin with probenecid reduced the renal clearance (CLr) of nemonoxacin by 22.6%, and increased the area under the plasma concentration time curve from time 0 to infinity (AUC0-infinity) by 26.2%. Coadministration of nemonoxacin with cimetidine reduced the CLr of nemonoxacin by 13.3% and increased AUC0-infinity by 9.4%. Coadministration of nemonoxacin with probenecid or cimetidine did not significantly affect the maximum concentration of nemonoxacin or the percentage of the administered dose recovered in the urine. CONCLUSION: Although probenecid reduced the CLr and increased the plasma exposure of nemonoxacin, these effects are unlikely to be clinically meaningful at therapeutic doses. Cimetidine had weaker, clinically meaningless effects on the pharmacokinetics of nemonoxacin. PMID- 26855563 TI - High-dose OxyContin to treat pain associated with bone metastasis in patients with small-cell lung cancer: a case study report. AB - Pain management is an important topic that has received extensive attention from clinical practitioners. Nearly all patients with malignant tumors suffer pain at the advanced stage of their disease. Oxycodone is a first-line choice for treating moderate-to-severe cancer-related pain, and OxyContin, a controlled release oxycodone hydrochloride tablet, is internationally recognized as a safe and effective opioid analgesic. OxyContin has the characteristics of both immediate release and sustained release, with a time to onset and peak similar to those of immediate-release morphine. It acts on both MU and kappa receptors and has been shown to be effective in treating different types of pain, especially neuropathic pain, theoretically without a dose cap. However, the dose is limited in clinical applications due to various factors that are likely to affect its analgesic effect and reduce patient quality of life. Cooperation with a patient's family members is required during the treatment of cancer pain. Chronic cancer pain has a long disease course, which could easily cause complex psychological symptoms due to their important role in the pain experience. Pain is controllable, and patients have a right to not experience pain. An optimal living state can be achieved through collaboration between physicians and patients. Rational personalized treatment of cancer pain can improve patient quality of life, relieve pain, and help prolong patient survival. This article reports the treatment procedure and adverse reactions in a patient who was treated with high dose OxyContin, with the aim of providing a reference for other clinical practitioners. PMID- 26855562 TI - The improvement effects of edible bird's nest on proliferation and activation of B lymphocyte and its antagonistic effects on immunosuppression induced by cyclophosphamide. AB - Edible bird's nest (EBN) is regarded as an immune-enhancing food in the People's Republic of China. The aim of this study is to demonstrate the efficiency of EBN in improving the immunity of mouse both in vivo and in vitro. We observed the effects of EBN on spleen lymphocytes proliferation and activation, as well as immunoglobulin isotypes as indicators. In addition, we evaluated the content of total sIgA in the intestinal juice to assess mucosal immunity. The results showed that EBN could promote the proliferation and activation of B-cells and increase IgE, IgA, IgM, and IgG3 levels. We also found that EBN extract can promote the secretion of sIgA in the small intestine. Using cyclophosphamide (CY), we established an immunosuppressed mouse model in which we identified a reversal influence on the ratio of CD3(+)/CD19(+) cells, which indicates that EBN also protects B-cells from the damage induced by CY. We also applied polymyxin B to exclude the interference of lipopolysaccharide throughout the experiment. In conclusion, we found that EBN can reduce the intestinal immune injury induced by CY by accelerating the proliferation and activation of B-cells and enhancing antibody secretion of B-cells. PMID- 26855564 TI - Saussurea tridactyla Sch. Bip.-derived polysaccharides and flavones reduce oxidative damage in ultraviolet B-irradiated HaCaT cells via a p38MAPK independent mechanism. AB - OBJECTIVE: To investigate whether Saussurea tridactyla Sch. Bip.-derived polysaccharides and flavones exert apoptosis-inhibiting effects in ultraviolet B (UVB)-irradiated HaCaT cells. METHODS: We divided HaCaT cells into low radiation UVB and high radiation UVB groups. Low radiation UVB and high radiation UVB groups were further divided into a control group, UVB radiation group (UVB group), S. tridactyla Sch. Bip.-derived polysaccharides and flavones low-dose group, and S. tridactyla Sch. Bip.-derived polysaccharides and flavones high-dose group. Cell viability and morphology were assayed by MTT and trypan blue staining. Superoxide dismutase activity, glutathione content, malondialdehyde content, and catalase activity test kits were used to detect superoxide dismutase activity, glutathione content, malondialdehyde content, and catalase activity, respectively. Cell apoptosis, intracellular Ca(2+) levels, and mitochondrial membrane potential (Deltapsi) were detected by flow cytometry. Protein levels were analyzed by Western blotting and immunofluorescence. RESULTS: S. tridactyla Sch. Bip.-derived polysaccharides and flavones were found to increase the absorbance of MTT, decrease cell death, alleviate the degree of cell edema, restore the cell morphology, reduce cell death fragments and chip phenomenon, increase superoxide dismutase activity, glutathione content, and catalase activity while decreasing the content of malondialdehyde, lowering the population of apoptotic cells, reducing the intracellular Ca(2+) fluorescence, increasing the mitochondrial membrane potential (Deltapsi), increasing the expressions of p 38, p-53, Bcl-2, and decreasing the expressions of Bax and active-caspase-3. CONCLUSION: S. tridactyla Sch. Bip.-derived polysaccharides and flavones can reduce cell apoptosis to protect HaCaT cells from oxidative damage after UVB irradiation; however, this effect does not occur via the p38MAPK pathway. PMID- 26855565 TI - Depot injectable atorvastatin biodegradable in situ gel: development, optimization, in vitro, and in vivo evaluation. AB - This study aimed to develop an optimized depot injectable atorvastatin (ATR) biodegradable in situ gel (ISG) system with minimum initial burst using a central composite design. The factors selected were poly (d, l-lactide-co-glycolide) (PLGA) concentration (X1), molecular weight of polyethylene glycol (PEG) (X2), and PEG concentration (X3). The independent variables were the initial burst of ATR after 2 (Y1) and 24 hours (Y2). The optimized formulation was investigated using scanning electron microscopy, Fourier transform infrared spectroscopy, and in vitro drug release in phosphate-buffered saline of pH 7.4 for 72 hours. The in vivo pharmacokinetic study of the optimized ATR-ISG and the corresponding PEG free ATR-ISG were conducted by intramuscular injection of a single dose (2 mg/kg) of ATR in male New Zealand White rabbits. A double-blind, randomized, parallel design was used in comparison with those of the marketed ATR tablet. Statistical analysis revealed that PLGA concentration and the molecular weight of PEG have pronounced effects on both Y1 and Y2. The optimized formulation was composed of 36.10% PLGA, PEG 6000, and 15.69% PEG, and exhibited characteristic in vitro release pattern with minimal initial burst. Incorporation of PEG in the formulation causes a slight decrease in the glass transition temperature value of PLGA, leading to a slight change in Fourier transform infrared spectroscopy spectrum due to possible interaction. Moreover, scanning electron microscopy photomicrograph showed smooth surface with disappearance of the cracks which characterize the surface of PEG-free formulation. The pharmacokinetic data for the optimized depot injectable ATR-ISG showed a significant (P<0.05) decrease in maximum plasma concentration from 547.62 to 346.84 ng/mL, and increasing time to reach the maximum plasma concentration from 12 to 72 hours in comparison with the marketed tablet. The optimized ATR-ISG formulation has shown minimal initial drug burst which confirms the suitability of the ISG system in the prolongation of drug release in patients with chronic long-term therapy. PMID- 26855566 TI - Impact of patient adherence on the cost-effectiveness of noninvasive tests for the initial diagnosis of Helicobacter pylori infection in the United States. AB - OBJECTIVE: Previous US-based economic models of noninvasive tests for diagnosis of Helicobacter pylori infection did not consider patient adherence or downstream costs of continuing infection. This analysis evaluated the long-term cost effectiveness of the urea breath test (UBT), fecal antigen test (FAT), and serology for diagnosis of H. pylori infection after incorporating information regarding test adherence. MATERIALS AND METHODS: A decision-analytic model incorporating adherence information evaluated the cost-effectiveness of the UBT, FAT, and serology for diagnosis of H. pylori infection. Positive test results led to first-line triple therapy; no further action was taken for nonadherence or negative results. Excess lifetime costs and reduced quality-adjusted life-years (QALYs) were estimated for patients with continuing H. pylori infection. RESULTS: In the base-case scenario with estimated adherence rates of 86%, 48%, and 86% for the UBT, monoclonal FAT, and serology, respectively, corresponding expected total costs were US$424.99, $466.41, and $404.98/patient. Test costs were higher for the UBT, but were fully or partially offset by higher excess lifetime costs for the monoclonal FAT and serology. The QALYs gained/patient with the UBT vs monoclonal FAT and serology were 0.86 and 0.27, respectively. The UBT was dominant vs the monoclonal FAT, leading to lower costs and higher QALYs; the UBT was cost-effective vs serology (incremental cost/QALY gained $74). CONCLUSION: Based on a comprehensive modeled analysis that included consideration of patient test adherence and long-term consequences resulting from continuing H. pylori infection, the UBT provided the greatest economic value among noninvasive tests for diagnosis of H. pylori infection, because of high patient adherence and excellent test performance. PMID- 26855567 TI - A Novel Histone Deacetylase Inhibitor, AR-42, Reactivates HIV-1 from Chronically and Latently Infected CD4+ T-cells. AB - Human immunodeficiency virus type 1 (HIV-1) latency is a major barrier to a cure of AIDS. Latently infected cells harbor an integrated HIV-1 genome but are not actively producing HIV-1. Histone deacetylase (HDAC) inhibitors, such as vorinostat (SAHA), have been shown to reactivate latent HIV-1. AR-42, a modified HDAC inhibitor, has demonstrated efficacy against malignant melanoma, meningioma, and acute myeloid leukemia and is currently used in clinical trials for non Hodgkin's lymphoma and multiple myeloma. In this study, we evaluated the ability of AR-42 to reactivate HIV-1 in the two established CD4+ T-cell line models of HIV-1 latency. In HIV-1 chronically infected ACH-2 cells, AR-42-induced histone acetylation was more potent and robust than that of vorinostat. Although AR-42 and vorinostat were equipotent in their ability to reactivate HIV-1, AR-42 induced maximal HIV-1 reactivation was twofold greater than vorinostat in ACH-2 and J-Lat (clone 9.2) cells. These data provide rationale for assessing the efficacy of AR-42-mediated HIV-1 reactivation within primary CD4+ T-cells. PMID- 26855568 TI - Differences in outcomes between GOLD groups in patients with COPD in the TIOSPIR((r)) trial. AB - BACKGROUND: The aim of this study was to evaluate whether Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification could predict mortality risk factors and whether baseline treatment intensity would relate to mortality within each group, using data from TIOSPIR((r)), the largest randomized clinical trial in COPD performed to date. METHODS: A total of 17,135 patients from TIOSPIR((r)) were pooled and grouped by GOLD grading (A-D) according to baseline Medical Research Council breathlessness score, exacerbation history, and spirometry. All-cause mortality and adjudicated cardiovascular (CV) and respiratory mortality were assessed. RESULTS: Of the 16,326 patients classified, 1,248 died on treatment. Group B patients received proportionally more CV treatment at baseline. CV mortality risk, but not all-cause mortality risk, was significantly higher in Group B than Group C patients (CV mortality - hazard ratio [HR] =1.74, P=0.004; all-cause mortality - HR =1.18, P=0.11). Group D patients had a higher incidence of all-cause mortality than Group B patients (10.9% vs 6.6%). Similar trends were observed regardless of respiratory or CV medication at baseline. In contrast, respiratory deaths increased consistently from Groups A-D (0.3%, 0.8%, 1.6%, and 4.2% of patients, respectively). CONCLUSION: The data obtained from the TIOSPIR((r)) trial, supporting earlier studies, suggest that proportionally more CV medication and CV deaths occur in GOLD Group B COPD patients, although deaths attributed to respiratory causes are more prevalent in Groups C and D. PMID- 26855569 TI - Targeted modulation of cell differentiation in distinct regions of the gastrointestinal tract via oral administration of differently PEG-PEI functionalized mesoporous silica nanoparticles. AB - Targeted delivery of drugs is required to efficiently treat intestinal diseases such as colon cancer and inflammation. Nanoparticles could overcome challenges in oral administration caused by drug degradation at low pH and poor permeability through mucus layers, and offer targeted delivery to diseased cells in order to avoid adverse effects. Here, we demonstrate that functionalization of mesoporous silica nanoparticles (MSNs) by polymeric surface grafts facilitates transport through the mucosal barrier and enhances cellular internalization. MSNs functionalized with poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and the targeting ligand folic acid in different combinations are internalized by epithelial cells in vitro and in vivo after oral gavage. Functionalized MSNs loaded with gamma-secretase inhibitors of the Notch pathway, a key regulator of intestinal progenitor cells, colon cancer, and inflammation, demonstrated enhanced intestinal goblet cell differentiation as compared to free drug. Drug loaded MSNs thus remained intact in vivo, further confirmed by exposure to simulated gastric and intestinal fluids in vitro. Drug targeting and efficacy in different parts of the intestine could be tuned by MSN surface modifications, with PEI coating exhibiting higher affinity for the small intestine and PEI-PEG coating for the colon. The data highlight the potential of nanomedicines for targeted delivery to distinct regions of the tissue for strict therapeutic control. PMID- 26855570 TI - Synthesis of antimicrobial silver nanoparticles through a photomediated reaction in an aqueous environment. AB - A fast, economical, and reproducible method for nanoparticle synthesis has been developed in our laboratory. The reaction is performed in an aqueous environment and utilizes light emitted by commercially available 1 W light-emitting diodes (lambda =420 nm) as the catalyst. This method does not require nanoparticle seeds or toxic chemicals. The irradiation process is carried out for a period of up to 10 minutes, significantly reducing the time required for synthesis as well as environmental impact. By modulating various reaction parameters silver nanoparticles were obtained, which were predominantly either spherical or cubic. The produced nanoparticles demonstrated strong antimicrobial activity toward the examined bacterial strains. Additionally, testing the effect of silver nanoparticles on the human keratinocyte cell line and human peripheral blood mononuclear cells revealed that their cytotoxicity may be limited by modulating the employed concentrations of nanoparticles. PMID- 26855571 TI - Liposomes coated with N-trimethyl chitosan to improve the absorption of harmine in vivo and in vitro. AB - In this study, harmine liposomes (HM-lip) were prepared through the thin-film hydration-pH-gradient method and then coated with N-trimethyl chitosan (TMC). Particle size, zeta potential, entrapment efficiency, and in vitro release of HM lip and TMC-coated harmine liposomes (TMC-HM-lip) were also determined. Sprague Dawley rats were further used to investigate the pharmacokinetics in vivo. Retention behavior in mouse gastrointestinal tract (GIT) was studied through high performance liquid chromatography and near-infrared imaging. Degradation was further evaluated through incubation with Caco-2 cell homogenates, and a Caco-2 monolayer cell model was used to investigate the uptake and transport of drugs. HM-lip and TMC-HM-lip with particle size of 150-170 nm, an entrapment efficiency of about 81%, and a zeta potential of negative and positive, respectively, were prepared. The release of HM from HM-lip and TMC-HM-lip was slower than that from HM solution and was sensitive to pH. TMC-HM-lip exhibited higher oral bioavailability and had prolonged retention time in GIT. HM-lip and TMC-HM-lip could also protect HM against degradation in Caco-2 cell homogenates. The uptake amount of TMC-HM-lip was higher than that of HM and HM-lip. TMC-HM-lip further demonstrated higher apparent permeability coefficient (P(app)) from the apical to the basolateral side than HM and HM-lip because of its higher uptake and capability to open tight junctions in the cell monolayers. TMC-HM-lip can prolong the retention time in the GIT, protect HM against enzyme degradation, and improve transport across Caco-2 cell monolayers, thus enhancing the oral bioavailability of HM. PMID- 26855572 TI - Anionic clay as the drug delivery vehicle: tumor targeting function of layered double hydroxide-methotrexate nanohybrid in C33A orthotopic cervical cancer model. AB - Methotrexate (MTX), an anticancer agent, was successfully intercalated into the anionic clay, layered double hydroxides to form a new nanohybrid drug. The coprecipitation and subsequent hydrothermal method were used to prepare chemically, structurally, and morphologically well-defined two-dimensional drug clay nanohybrid. The resulting two-dimensional drug-clay nanohybrid showed excellent colloidal stability not only in deionized water but also in an electrolyte solution of Dulbecco's Modified Eagle's Medium with 10% fetal bovine serum, in which the average particle size in colloid and the polydispersity index were determined to be around 100 and 0.250 nm, respectively. The targeting property of the nanohybrid drug was confirmed by evaluating the tumor-to-blood and tumor-to-liver ratios of the MTX with anionic clay carrier, and these ratios were compared to those of free MTX in the C33A orthotopic cervical cancer model. The biodistribution studies indicated that the mice treated with the former showed 3.5-fold higher tumor-to-liver ratio and fivefold higher tumor-to-blood ratio of MTX than those treated with the latter at 30 minutes postinjection. PMID- 26855573 TI - Impact of single-walled carbon nanotubes on the embryo: a brief review. AB - Carbon nanotubes (CNTs) are considered one of the most interesting materials in the 21st century due to their unique physiochemical characteristics and applicability to various industrial products and medical applications. However, in the last few years, questions have been raised regarding the potential toxicity of CNTs to humans and the environment; it is believed that the physiochemical characteristics of these materials are key determinants of CNT interaction with living cells and hence determine their toxicity in humans and other organisms as well as their embryos. Thus, several recent studies, including ours, pointed out that CNTs have cytotoxic effects on human and animal cells, which occur via the alteration of key regulator genes of cell proliferation, apoptosis, survival, cell-cell adhesion, and angiogenesis. Meanwhile, few investigations revealed that CNTs could also be harmful to the normal development of the embryo. In this review, we will discuss the toxic role of single-walled CNTs in the embryo, which was recently explored by several groups including ours. PMID- 26855574 TI - Quantitative [Fe]MRI of PSMA-targeted SPIONs specifically discriminates among prostate tumor cell types based on their PSMA expression levels. AB - We report the development, experimental verification, and application of a general theory called [Fe]MRI (pronounced fem-ree) for the non-invasive, quantitative molecular magnetic resonance imaging (MRI) of added magnetic nanoparticles or other magnetic contrast agents in biological tissues and other sites. [Fe]MRI can easily be implemented on any MRI instrument, requiring only measurements of the background nuclear magnetic relaxation times (T1, T2) of the tissue of interest, injection of the magnetic particles, and the subsequent acquisition of a pair of T1-weighted and T2-weighted images. These images, converted into contrast images, are subtracted to yield a contrast difference image proportional to the absolute nanoparticle, iron concentration, ([Fe]) image. [Fe]MRI was validated with the samples of superparamagnetic iron oxide nanoparticles (SPIONs) both in agarose gels and bound to human prostate tumor cells. The [Fe]MRI measurement of the binding of anti-prostate specific membrane antigen (PSMA) conjugated SPIONs to PSMA-positive LNCaP and PSMA-negative DU145 cells in vitro allowed a facile discrimination among prostate tumor cell types based on their PSMA expression level. The low [Fe] detection limit of ~2 MUM for SPIONs allows sensitive MRI of added iron at concentrations considerably below the US Food and Drug Administration's human iron dosage guidelines (<90 MUM, 5 mg/kg). PMID- 26855575 TI - Silver nanoparticles/chitosan oligosaccharide/poly(vinyl alcohol) nanofiber promotes wound healing by activating TGFbeta1/Smad signaling pathway. AB - Wound healing occupies a remarkable place in everyday pathology and remains a challenging clinical problem. In our previous study, we prepared a silver nanoparticle/chitosan oligosaccharide/poly(vinyl alcohol) (PVA/COS-AgNPs) nanofiber via electrospinning and revealed that it could promote wound healing; however, the healing mechanism remained unknown. Therefore, we aimed to clarify the mechanism underlying the accelerated healing effect of the PVA/COS-AgNPs nanofiber. The TGFbeta1/Smad signaling pathway is actively involved in wound healing. Considering the key role of this signaling pathway in wound healing, our preliminary study showed that the TGFbeta1 level was significantly increased during the early stage of wound healing. Thus, in this study, hematoxylin-eosin, Masson's trichrome, immunofluorescent staining, hydroxyproline content, quantitative real-time polymerase chain reaction, and Western blot analyses were used to analyze the wound healing in a rat model treated with gauze, the PVA/COS AgNPs nanofiber, and the nanofiber plus SB431542 (an inhibitor of TGFbeta1 receptor kinase). The results showed that the PVA/COS-AgNPs nanofiber promoted wound healing and upregulated the expression levels of cytokines associated with the TGFbeta1/Smad signaling pathway such as TGFbeta1, TGFbetaRI, TGFbetaRII, collagen I, collagen III, pSmad2, and pSmad3. Inhibiting this pathway with SB431542 resulted in prevention of the PVA/COS-AgNPs nanofiber-associated salutary effects on the early stage of wound healing and relative cytokines expression. In conclusion, the wound healing effect of the PVA/COS-AgNPs nanofiber involves activation of the TGFbeta1/Smad signaling pathway. PMID- 26855577 TI - Update on eating disorders: current perspectives on avoidant/restrictive food intake disorder in children and youth. AB - Avoidant/restrictive food intake disorder (ARFID) is a new eating disorder diagnosis that was introduced in the Diagnostic and Statistical Manual of Mental Disorders (DSM) fifth edition. The fourth edition of the DSM had failed to adequately capture a cohort of children, adolescents, and adults who are unable to meet appropriate nutritional and/or energy needs, for reasons other than drive for thinness, leading to significant medical and/or psychological sequelae. With the introduction of ARFID, researchers are now starting to better understand the presentation, clinical characteristics, and complexities of this disorder. This article outlines the diagnostic criteria for ARFID with specific focus on children and youth. A case example of a patient with ARFID, factors that differentiate ARFID from picky eating, and the estimated prevalence in pediatric populations are discussed, as well as clinical and treatment challenges that impact health care providers providing treatment for patients. PMID- 26855576 TI - Abnormal resting-state functional connectivity within the default mode network subregions in male patients with obstructive sleep apnea. AB - BACKGROUND AND OBJECTIVE: Abnormal resting-state functional connectivity (rs-FC) between the central executive network and the default mode network (DMN) in patients with obstructive sleep apnea (OSA) has been reported. However, the effect of OSA on rs-FC within the DMN subregions remains uncertain. This study was designed to investigate whether the rs-FC within the DMN subregions was disrupted and determine its relationship with clinical symptoms in patients with OSA. METHODS: Forty male patients newly diagnosed with severe OSA and 40 male education- and age-matched good sleepers (GSs) underwent functional magnetic resonance imaging (fMRI) examinations and clinical and neuropsychologic assessments. Seed-based region of interest rs-FC method was used to analyze the connectivity between each pair of subregions within the DMN, including the medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), hippocampus formation (HF), inferior parietal cortices (IPC), and medial temporal lobe (MTL). The abnormal rs-FC strength within the DMN subregions was correlated with clinical and neuropsychologic assessments using Pearson correlation analysis in patients with OSA. RESULTS: Compared with GSs, patients with OSA had significantly decreased rs-FC between the right HF and the PCC, MPFC, and left MTL. However, patients with OSA had significantly increased rs-FC between the MPFC and left and right IPC, and between the left IPC and right IPC. The rs-FC between the right HF and left MTL was positively correlated with rapid eye movement (r=0.335, P=0.035). The rs-FC between the PCC and right HF was negatively correlated with delayed memory (r=-0.338, P=0.033). CONCLUSION: OSA selectively impairs the rs-FC between right HF and PCC, MPFC, and left MTL within the DMN subregions, and provides an imaging indicator for assessment of cognitive dysfunction in OSA patients. PMID- 26855578 TI - cAMP/PKA/CREB/GLT1 signaling involved in the antidepressant-like effects of phosphodiesterase 4D inhibitor (GEBR-7b) in rats. AB - OBJECTIVES: GEBR-7b, a potential phosphodiesterase 4D inhibitor, has been shown to have memory-enhancing effects in rodents. However, it is still unknown whether GEBR-7b also has the antidepressant-like effects in rats. Herein, we examined the potential of GEBR-7b to attenuate depression-like behaviors in the rat model of depression induced by chronic unpredictable stress (CUS). Next, we also investigated the alterations of cyclic adenosine monophosphate (cAMP), protein kinase A (PKA) catalytic subunit (PKAca), cAMP response element-binding (CREB), and glutamate transporter 1 (GLT1) levels produced by GEBR-7b in the rats model of depression. METHODS: Effects of GEBR-7b on CUS (35 days)-induced depression like behaviors were examined by measuring immobility time in the forced swimming test (FST). Hippocampal cAMP levels were examined by enzyme-linked immunosorbent assay, whereas PKAca, phosphorylation of CREB (pCREB), CREB, and GLT1 in the hippocampus of rats were subjected to Western blot analysis. RESULTS: CUS exposure caused a depression-like behavior evidenced by the increased immobility time in FST. Depression-like behavior induced by CUS was accompanied by a significant increased GLT, decreased cAMP, PKAca, pCREB activities in hippocampus. However, repeated GEBR-7b administration significantly reversed CUS induced depression-like behavior and changes of cAMP/PKA/CREB/GLT1 signaling. No alteration was observed in locomotor activity in open field test. CONCLUSION: These findings indicate that GEBR-7b reversed the depression-like behaviors induced by CUS in rats, which is at least in part mediated by modulating cAMP, PKAca, pCREB, and GLT1 levels in the hippocampus of rats, supporting its neuroprotective potential against behavioral and biochemical dysfunctions induced by CUS. PMID- 26855579 TI - Reduction of group A beta-hemolytic streptococcus pharyngo-tonsillar infections associated with use of the oral probiotic Streptococcus salivarius K12: a retrospective observational study. AB - Recurrent pharyngo-tonsillar infections caused by group A beta-hemolytic streptococci (GABHS) occur frequently in young children, and the treatment of these infections contributes substantially to the total current requirement for antibiotic prescribing. Our study goal was to assess through a retrospective observational analysis whether the administration of the oral probiotic, Streptococcus salivarius K12 (SsK12), could reduce the occurrence of GABHS pharyngo-tonsillar infections in children who had a recent history of recurrent episodes of these infections. Twelve primary care pediatricians identified, through their databases, a total of 130 children who had experienced recurrent GABHS pharyngo-tonsillar infections over a period of at least 6-12 months prior to their inclusion in the study. Of these children, 76 then undertook a 90-day program requiring once-a-day dosing with a commercially available (Bactoblis) lozenge containing SsK12. No probiotic supplement was given to the remaining 54 (control) children. Each subject was monitored for the occurrence of GABHS pharyngo-tonsillitis and also for acute otitis media, bronchitis, sinusitis, and bronchopneumonia for at least 12 months following their entry to the study. Even 9 months after the use of SsK12 had been stopped, the probability of new GABHS infections was significantly lower (P>0.001) when compared to the period before dosing commenced. When compared to the untreated children, those taking SsK12 appear to have had significantly fewer GABHS infections both during the 90-day period of prophylaxis and during the following 9 months (P<0.001). These observations are supportive of the use of probiotic SsK12 for the control of recurrent GABHS pharyngo-tonsillar infections in children, and as an associated benefit, the use of this probiotic could lead to reduced antibiotic consumption. Follow-up controlled prospective studies should now be initiated in order to further establish the efficacy of this newly emerging prophylactic strategy. PMID- 26855580 TI - Does the treatment of type 2 diabetes mellitus with the DPP-4 inhibitor vildagliptin reduce HbA1c to a greater extent in Japanese patients than in Caucasian patients? AB - BACKGROUND: Previous work suggests that Japanese patients with type 2 diabetes mellitus (T2DM) may respond more favorably to a DPP-4 (dipeptidyl peptidase-4) inhibitor than Caucasians. We aimed to compare the efficacy of the DPP-4 inhibitor vildagliptin (50 mg twice daily [bid]) between Japanese and Caucasian populations. METHODS: This analysis pooled data from 19 studies of drug-naive patients with T2DM who were treated for 12 weeks with vildagliptin 50 mg bid as monotherapy. The pool comprised Japanese patients (n=338) who had been treated in Japan and Caucasian patients (n=1,275) who were treated elsewhere. Change from baseline (Delta) in glycated hemoglobin (HbA1c) at 12 weeks (in millimoles per mole) versus baseline HbA1c (both in percentage National Glycohemoglobin Standardization Program units [NGSP%] and millimoles per mole) for each population was reported. Universal HbA1c in millimoles per mole was calculated from either the Japanese Diabetes Society or the NGSP% HbA1c standards. RESULTS: At baseline, mean values for Japanese and Caucasian patients, respectively, were as follows: age, 59 years and 56 years; % male, 69% and 57%. The average HbA1c was reduced from 7.90% to 6.96% (Japanese Diabetes Society) and from 8.57% to 7.50% (United States National Glycohemoglobin Standardization Program), while HbA1c was reduced from 63 mmol/mol to 53 mmol/mol and from 70 mmol/mol to 58 mmol/mol in Japanese and Caucasians, respectively. DeltaHbA1c increased with increasing baseline in both populations. The slopes were the same (0.41, r (2)=0.36; and 0.41, r (2)=0.15), and the intercepts were 15.4 mmol/mol and 17.2 mmol/mol, respectively. In Japanese patients, mean DeltaHbA1c was greater by 1.7 mmol/mol (0.2% NGSP HbA1c) at any given baseline HbA1c than in Caucasians (P=0.01). CONCLUSION: The present pooled analysis suggests that Japanese patients respond better to vildagliptin treatment compared with Caucasians. However, when glycemic control was corrected by using the same glycemic standard, the difference in HbA1c reduction between these populations was not clinically meaningful. PMID- 26855582 TI - Anxiety mediates the effect of smoking on insomnia in people with asthma: evidence from the HUNT3 study. AB - OBJECTIVE: The aim of this study was to investigate factors related to insomnia in a cohort of people with asthma. DESIGN: This secondary analysis utilized cross sectional data from the Norwegian Nord-Trondelag Health Study, a population-based health survey (n=50,807). PARTICIPANTS: We used self-reported data from 1,342 men and women with a physician-confirmed asthma diagnosis ranging in age from 19.5 to 91 years. MEASUREMENTS: Data on sleep, lifestyle variables (smoking and exercise), anxiety, and depression were included. An insomnia scale and asthma impact scale were constructed using factor analysis. Hierarchical series of multiple regression models were used to investigate direct and mediational relationships between the study variables and insomnia. RESULTS: The hierarchical models revealed significant independent contributions of female sex, higher age, not exercising, asthma impact, anxiety, and depression on insomnia (R (2)=25.2%). Further, these models suggested that the impact of smoking on insomnia was mediated by anxiety, and that the beneficial impact of exercise was mitigated by depression symptoms. CONCLUSION: Smokers with asthma have more insomnia, and this relationship may be mediated by anxiety. Further, people with asthma who experience depression symptoms are less likely to benefit from physical exercise as a method to enhance sleep quality. Our findings would suggest that helping smokers to manage their anxiety and depression through behavioral methods may reduce their insomnia symptoms, and enable them to engage in other health enhancing pursuits, such as physical exercise. PMID- 26855581 TI - Management of Charcot-Marie-Tooth disease: improving long-term care with a multidisciplinary approach. AB - Charcot-Marie-Tooth (CMT) disease is the most common inherited neuropathy and one of the most common inherited diseases in humans. The diagnosis of CMT is traditionally made by the neurologic specialist, yet the optimal management of CMT patients includes genetic counselors, physical and occupational therapists, physiatrists, orthotists, mental health providers, and community resources. Rapidly developing genetic discoveries and novel gene discovery techniques continue to add a growing number of genetic subtypes of CMT. The first large clinical natural history and therapeutic trials have added to our knowledge of each CMT subtype and revealed how CMT impacts patient quality of life. In this review, we discuss several important trends in CMT research factors that will require a collaborative multidisciplinary approach. These include the development of large multicenter patient registries, standardized clinical instruments to assess disease progression and disability, and increasing recognition and use of patient-reported outcome measures. These developments will continue to guide strategies in long-term multidisciplinary efforts to maintain quality of life and preserve functionality in CMT patients. PMID- 26855583 TI - MicroRNA-497 inhibits cell proliferation, migration, and invasion by targeting AMOT in human osteosarcoma cells. AB - MicroRNAs (miRNAs) have a role in the development and progression of human malignancy. The expression of miR-497 is decreased in malignant tumors, which suggests a role for miR-497 as a tumor suppressor. Angiomotin is encoded by the AMOT gene, which is a target for miR-497. Angiomotin has a role in angiogenesis, cell proliferation, and invasion in human malignancies, including osteosarcoma. However, the role of miR-497 in human osteosarcoma is unknown. This preliminary study included human osteosarcoma tissues and normal tissues from 20 patients, the osteosarcoma cell lines, MG-63, SAOS-2, U-2 OS, and the human osteoblast cell line hFOB (OB3). Western blots for angiomotin and quantitative real-time polymerase chain reaction for the expression of miR-497 and AMOT were performed. Knockdown studies were performed using RNA interference and transfection studies used miR-497 mimics. Quantitative cell migration assays were performed, and cell apoptosis was studied by flow cytometry. Osteosarcoma cells and cell lines showed reduced expression of miR-497 and increased expression of angiomotin. Transfection of osteosarcoma cells with miR-497 mimics suppressed the expression of angiomotin. Results from a dual-luciferase reporter system supported AMOT as a direct target gene of miR-497. Knockdown of AMOT using RNA interference resulted in inhibition of osteosarcoma cell proliferation, migration, and invasion. These preliminary studies support a role for miR-497 as a suppressor of AMOT gene expression in human osteosarcoma cells, resulting in suppression of tumor cell proliferation and invasion. Further studies are recommended to investigate the role of miR-497 in osteosarcoma and other malignant mesenchymal tumors. PMID- 26855584 TI - Cost-effectiveness of radical hysterectomy with adjuvant radiotherapy versus radical radiotherapy for FIGO stage IIB cervical cancer. AB - OBJECTIVE: Recent literature reports that radical hysterectomy followed by adjuvant radiotherapy has comparable progression-free survival and overall survival compared to radical radiotherapy for International Federation of Gynecology and Obstetrics stage IIB cervical cancer. Now, we evaluate the cost effectiveness (CE) of these two treatment regimens. PRIMARY AND SECONDARY OUTCOME MEASURES: A decision-tree model was constructed comparing CE between treatment arms using the published studies for overall survival rates and treatment-related toxicity rates for 5 years. The cost data were obtained from the hospital system of the First Affiliated Hospital of Xi'an Jiaotong University. Effectiveness was measured as quality-adjusted life year (QALY). Treatment arms were compared with regard to costs and life expectancy using incremental CE ratio, and the results were presented using costs per QALY. RESULTS: The mean cost was $10,872 for radical hysterectomy followed by adjuvant radiotherapy versus $5,702 for radical radiotherapy. The incremental CE ratio for surgery-based treatment compared to radiotherapy-based treatment was -$76,453 per QALY. CONCLUSION: Radical radiotherapy would be a cost-effective method for FIGO stage IIB cervical cancer and would be favored in settings where resources are limited. PMID- 26855585 TI - Association between the Cyclin D1 G870A polymorphism and the susceptibility to and prognosis of upper aerodigestive tract squamous cell carcinomas: an updated meta-analysis. AB - PURPOSE: Several publications have investigated the association between the Cyclin D1 G to A substitution at nucleotide 870 (CCND1 G870A) polymorphism and squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT), but their conclusions still remain controversial. We conducted a meta-analysis to precisely evaluate this association. PATIENTS AND METHODS: We electronically searched the Chinese National Knowledge Infrastructure, PubMed, and Embase (up to January 2015) databases for case-control studies on the association between the CCND1 G870A polymorphism and SCC of the UADT, and 23 studies were included in total. RESULTS: The meta-analysis results showed that there was a significant association between the CCND1 G870A polymorphism and the risk of SCC of the UADT (AA vs GG: odds ratio [OR] =1.33, 95% confidence interval [CI] =1.01-1.74, P<0.001 for heterogeneity; GA/AA vs GG: OR =1.24, 95% CI =1.01-1.51, P<0.001 for heterogeneity; AA vs GA/GG: OR =1.16, 95% CI =0.97-1.39, P<0.001 for heterogeneity; allele A vs allele G: OR =1.14, 95% CI =1.00-1.30, P<0.001 for heterogeneity; GA vs GG: OR =1.18, 95% CI =0.98-1.42, P<0.001 for heterogeneity). However, when analyzing prognosis, allele G was a potential risk factor for poor tumor differentiation (AA vs GA/GG: OR =2.60, 95% CI =1.15-5.86, P=0.836 for heterogeneity) and reduced disease-free intervals (OR =2.08, 95% CI =1.17-3.69, P=0.134 for heterogeneity). In the subgroup analysis, the cancer susceptibility of Asian groups, population-based control groups, nasopharyngeal cancer groups, and esophageal SCC groups were more likely to be affected by the CCND1 G870A polymorphism. No significant publication bias was found in our analysis (P=0.961 for Egger's test and P=0.245 for Begg's test). CONCLUSION: The results of the present meta-analysis suggest that the variant CCND1 870A allele might confer an elevated risk of SCC of the UADT, particularly among Asians and individuals who have esophageal or nasopharyngeal cancers. Moreover, the CCND1 870A allele might also confer better tumor differentiation grades and longer disease-free intervals. PMID- 26855586 TI - High levels of EGFR expression in tumor stroma are associated with aggressive clinical features in epithelial ovarian cancer. AB - PURPOSE: The aim of this study was to investigate the clinical significance and biological function of epidermal growth factor receptor (EGFR) expressed in tumor stroma of epithelial ovarian cancer. METHODS: Immunohistological staining of EGFR was evaluated in 242 patients with epithelial ovarian cancer. The correlations of EGFR expression in tumor stroma with clinicopathological features and with the expression level of Ki-67 were analyzed by SPSS software. Kaplan-Meier analysis and the Cox proportional hazard model were used to analyze the effect of EGFR expression in tumor stroma on the prognosis of patients with epithelial ovarian cancer. Meanwhile, the activities of proliferation and migration of tumor cells were detected when EGFR overexpressed in stroma cells. RESULTS: EGFR expression in tumor stroma correlated significantly with clinical stage (chi (2)=7.002, P=0.008) and distant metastases (chi (2)=16.59, P<0.001). Furthermore, there was a significantly positive correlation between the level of EGFR expressed in tumor stroma and the level of Ki-67 expressed in tumor cells (chi (2)=6.120, P=0.013). Patients with high EGFR expression level in tumor stroma showed poor survival (P=0.002). Multivariate analysis showed that high expression of EGFR in tumor stroma was an independent predictor for epithelial ovarian cancer patients (hazard ratio =1.703; 95% confidence interval 1.125-2.578, P=0.012). Furthermore, stroma cells overexpressing EGFR could promote the proliferation and migration of adjacent tumor cells. CONCLUSION: High expression of EGFR in tumor stroma correlates with aggressive clinical features in epithelial ovarian cancer, and is an independent prognostic factor. PMID- 26855587 TI - Expression and prognostic significance of contactin 1 in human hepatocellular carcinoma. AB - BACKGROUND: CNTN1, a member of the CNTN family of neural cell-recognition molecules, is involved in tumor invasion and metastasis. Although the expression of CNTN1 has been reported in several human malignancies, the expression of CNTN1 in hepatocellular carcinoma (HCC) and its correlation with prognosis remain unclear. The aim of this study was to evaluate the expression of CNTN1 and determine the clinicopathological parameters and prognostic value of CNTN1 in HCC patients. MATERIALS AND METHODS: Quantitative real-time polymerase chain-reaction and Western blotting assays were performed to assess messenger RNA and protein levels of CNTN1 in 20 matched HCC specimens. The clinical and prognostic significance of CNTN1 in 90 cases of HCC was determined by immunohistochemistry. RESULTS: CNTN1 expression was higher in HCC compared to the expression found in adjacent tissues at both messenger RNA and protein levels (P<0.01). Notably, immunohistochemical results revealed that CNTN1 expression was significantly higher in HCC compared to adjacent tissues (54.4% vs 12.2%, P=0.01). Furthermore, positive CNTN1 expression was associated with tumor size, tumor capsulae, status of metastasis, and tumor-node-metastasis stage. Kaplan-Meier survival analysis showed that high CNTN1 was correlated with reduced overall survival (OS) rate (P<0.001) and disease-free survival (DFS) rate (P=0.001). Multivariate analysis identified CNTN1 as an independent poor prognostic factor of OS and DFS in HCC patients (P=0.007 and P=0.002, respectively). CONCLUSION: Our results suggest that CNTN1 could play an important role in HCC and serve as an independent unfavorable prognostic factor for OS and DFS and a potential therapeutic target for HCC. PMID- 26855588 TI - Polymorphisms in pre-miRNA genes and cooking oil fume exposure as well as their interaction on the risk of lung cancer in a Chinese nonsmoking female population. AB - BACKGROUND: MicroRNAs (miRNAs) are suggested to be very important in the development of lung cancer. This study assesses the association between polymorphisms in miRNA-related (miR)-26a-1, miR-605, and miR-16-1 genes and risk of lung cancer, as well as the effect of gene-environment interaction between miRNA polymorphisms and cooking fume exposure on lung cancer. METHODS: A case control study including 268 diagnosed nonsmoking female lung cancer patients and 266 nonsmoking female controls was carried out. Three miRNA polymorphisms (miR 26a-1 rs7372209, miR-605 rs2043556, and miR-16-1 rs1022960) were analyzed. Both additive and multiplicative interactions were assessed. RESULTS: MiR-16-1 rs1022960 may be associated with the risk of lung cancer. Carriers with TT genotype of miR-16-1 rs1022960 were observed to have a decreased risk of lung cancer compared with CC and CT genotype carriers (odds ratio =0.550, 95% confidence interval =0.308-0.983, P=0.044). MiR-26a-1 rs7372209 and miR-605 rs2043556 showed no statistically significant associations with lung cancer risk. There were no significant associations between the three single nucleotide polymorphisms and lung adenocarcinoma. People with exposure to both risk genotypes of miR-26a-1 rs7372209 and cooking oil fumes were more likely to develop lung cancer than those with only genetic risk factor or cooking oil fumes (odds ratios were 2.136, 1.255, and 1.730, respectively). The measures of biological interaction and logistic models indicate that gene-environment interactions were not statistically significant on additive scale or multiplicative scale. CONCLUSION: MiR-16-1 rs1022960 may be associated with the risk of lung cancer in a Chinese nonsmoking female population. The interactions between miRNA polymorphisms (miR-26a-1 rs7372209, miR-605 rs2043556, and miR-16-1 rs1022960) and cooking oil fumes were not statistically significant. PMID- 26855589 TI - Efficacy and safety of ultrasound-guided continuous hyperthermic intraperitoneal perfusion chemotherapy for the treatment of malignant ascites: a midterm study of 36 patients. AB - BACKGROUND: This study aimed to evaluate the efficacy and safety of ultrasound guided continuous hyperthermic intraperitoneal perfusion chemotherapy (CHIPC) for the treatment of malignant ascites (MA). METHODS: Between July 2011 and June 2013, 36 MA patients were prospectively and consecutively hospitalized for three cycles of elective CHIPC under ultrasound guidance, maintained at a constant flow rate of 400-600 mL/min normal saline containing 5-fluorouracil plus mitomycin or carboplatin and at a constant temperature of 43 degrees C+/-0.2 degrees C, for 90 minutes. Main outcome measures were ascites resolution, Karnofsky performance status (KPS), and serum tumor biomarkers at 2 weeks after the last cycle of CHIPC. All the patients underwent uneventful CHIPC as scheduled, and vital signs remained stable over CHIPC. RESULTS: At 2 weeks after the last cycle of CHIPC, MA completely and partially resolved in 26 (72.2%) patients and eight (22.2%) patients, respectively; mean KPS score increased from pretreatment 61+/-9 to posttreatment 76+/-9 (P<0.001), and serum carcinoembryonic antigen and carbohydrate antigens 12-5 and 19-9 significantly decreased (all P<0.01). CONCLUSION: The current study indicated that ultrasound-guided CHIPC is an effective and safe palliative treatment modality for MA with respect to MA resolution, patient's general well-being, and systemic disease control. The long term benefit of CHIPC on overall survival remains to be investigated in MA patients. PMID- 26855590 TI - TDRG1 functions in testicular seminoma are dependent on the PI3K/Akt/mTOR signaling pathway. AB - Human testis development-related gene 1 (TDRG1) is a recently identified gene that is expressed exclusively in the testes and promotes the development of testicular germ cell tumors. In this study, the role of TDRG1 in the development of testicular seminoma, which is the most common testicular germ cell tumor, was further investigated. Based on polymerase chain reaction, Western blotting, and immunohistochemistry tests, both gene and protein expression levels of TDRG1 were significantly upregulated in testicular seminoma tissues compared with normal testicular tissues. Additionally, the levels of phosphoinositide-3 kinase (PI3K)/p110 and Akt phosphorylation were dramatically upregulated in testicular seminoma tissues. Accordingly, in our cell experiment, seminoma TCam-2 cells were subjected to different treatments: the TDRG1 knockout, TDRG1 overexpression, PI3K inhibition (LY294002 administration), or PI3K activation (insulin-like growth factor-1 administration). Cell proliferation, the proliferation index, apoptosis rate, cell adhesive capacity, and cell invasion capability were assessed. Cells with both TDRG1 knockout and PI3K inhibition exhibited decreased cell proliferation, proliferation indexes, cell adhesion capacity, and cell invasion capability and increased apoptosis rates. Most of these effects were reversed by TDRG1 overexpression or PI3K activation, indicating that both TDRG1- and PI3K mediated signaling promote proliferation and invasion of testicular seminoma cells. The knockout of TDRG1 significantly decreased the phosphorylation levels of PI3K/p85, PI3K/p110, Akt, and mammalian target of rapamycin (mTOR; Ser(2448)). Except for PI3K/p110, TDRG1 overexpression had the opposite effects on phosphorylation levels. Phosphorylated mTOR at Ser(2481) and Thr(2446) was not affected by TDRG1 or PI3K in our tests. Thus, these results indicate that TDRG1 promotes the development and migration of seminoma cells via the regulation of the PI3K/Akt/mTOR signaling pathway; this contributes to an understanding of the precise mechanisms underlying the development and migration of seminomas and lays a theoretical foundation for the development of appropriate therapies. PMID- 26855591 TI - New developments in the management of chronic lymphocytic leukemia: role of ofatumumab. AB - Ofatumumab is one of the three anti-CD20 monoclonal antibodies currently available for the treatment of chronic lymphocytic leukemia (CLL). The US Food and Drug Administration (FDA) approved the use of ofatumumab in patients with CLL refractory to fludarabine and alemtuzumab in 2009, and the European Medicines Agency (EMA) granted approval for the same indication in 2010. Subsequent positive results of ofatumumab in combination with chlorambucil in treatment naive patients led the FDA in April 2014 to approve the use of this combination for first-line treatment of patients with CLL for whom fludarabine-based therapy is considered inappropriate. Later that year, the EMA approved the use of ofatumumab in combination with chlorambucil or bendamustine for the same indication. Ofatumumab has also shown potential as maintenance therapy for patients with relapsed CLL; an application to broaden the label for ofatumumab as maintenance therapy was submitted earlier this year to the EMA and FDA. Finally, ofatumumab has shown promising activity in combination with ibrutinib or idelalisib in relapsed/refractory CLL patients; combinations of ofatumumab with B cell-receptor pathway inhibitors could represent another potential use of this antibody in the near future. PMID- 26855592 TI - Enrichment of CD44 in basal-type breast cancer correlates with EMT, cancer stem cell gene profile, and prognosis. AB - Cluster of differentiation 44 (CD44) is a transmembrane glycoprotein that serves as the receptor for the extracellular matrix component hyaluronic acid. CD44 has been reported to play key roles in cell proliferation, motility, and survival, but its role in breast cancer remains controversial. In this study, we conducted a meta-analysis. A total of 23 published Gene Expression Omnibus databases were included to evaluate the association between CD44 mRNA expression and clinicopathological characteristics or prognosis of the patients with breast cancer. Our analysis revealed that CD44 expression was associated with clinicopathological features, including the histological grade, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status. Higher levels of CD44 expression were observed in the basal subtype of breast cancer both at the mRNA and protein levels (odds ratio [OR] =2.08, 95% confidence interval [CI]: 1.72-2.52; OR =2.11, 95% CI: 1.67-2.68). Patients with CD44 overexpression exhibited significantly worse overall survival (hazard ratio =1.27; 95% CI: 1.04-1.55). Whole gene profile analysis revealed that CD44 expression was enriched in basal-type breast cancer and correlated with epithelial-mesenchymal transition and cancer stem cell gene profiles. In summary, our analyses indicated that CD44 potentially might be a prognostic marker for breast cancer and thus can serve as a therapeutic target for basal-type breast cancer. PMID- 26855593 TI - Upregulated long intergenic noncoding RNA KRT18P55 acts as a novel biomarker for the progression of intestinal-type gastric cancer. AB - BACKGROUND: Long noncoding RNAs (lncRNAs) with dysregulated expression levels have been investigated in numerous types of different cancer. Whether lncRNAs can predict the progression of gastric cancer (GC) still remains largely unclear. The aim of our study was to investigate whether KRT18P55, a novel intergenic lncRNA, can be a predictive biomarker for GC. METHODS: To determine the expression levels of KRT18P55 in GC, we evaluated it in five GC cell lines (SGC-7901, MGC-803, BGC 823, AGS, and HG27) and 97 GC tissue samples in comparison with a normal control by quantitative polymerase chain reaction. In addition, the association with patient clinicopathological characteristics was analyzed to identify the clinical significance of KRT18P55. We also used publicly accessible data from The Cancer Genome Atlas (TCGA) to further verify the expression levels and clinical significance of KRT18P55. Furthermore, a receiver operating characteristic curve was also conducted to evaluate the diagnostic value of KRT18P55 for GC. RESULTS: A significant upregulation was observed in GC cell lines (P<0.01) and tissue samples (P<0.01). This finding was consistent with the results of 29 pairs of GC tissue samples from TCGA (P<0.01). Additionally, we indicated that the increased expression of KRT18P55 was related to the progression of intestinal type (P=0.032), which was also supported by results of independent GC cohorts from TCGA (P<0.01). However, we did not find significant difference in prognosis between patients with high and low expression of KRT18P55 (P>0.05). Finally, KRT18P55 showed potential diagnostic value for GC with an area under the receiver operating characteristic curve of 0.733 (P<0.01). CONCLUSION: Upregulated KRT18P55 was a novel biomarker for the progression of GC, especially for the intestinal type. PMID- 26855595 TI - Ignoring the sacroiliac joint in chronic low back pain is costly. AB - BACKGROUND: Increasing evidence supports minimally invasive sacroiliac joint (SIJ) fusion as a safe and effective treatment for SIJ dysfunction. Failure to include the SIJ in the diagnostic evaluation of low back pain could result in unnecessary health care expenses. DESIGN: Decision analytic cost model. METHODS: A decision analytic model calculating 2-year direct health care costs in patients with chronic low back pain considering lumbar fusion surgery was used. RESULTS: The strategy of including the SIJ in the preoperative diagnostic workup of chronic low back pain saves an expected US$3,100 per patient over 2 years. Cost savings were robust to reasonable ranges for costs and probabilities, such as the probability of diagnosis and the probability of successful surgical treatment. CONCLUSION: Including the SIJ as part of the diagnostic strategy in preoperative patients with chronic low back pain is likely to be cost saving in the short term. PMID- 26855596 TI - Assessment of efficacy, safety, and tolerability of 4-n-butylresorcinol 0.3% cream: an Indian multicentric study on melasma. AB - INTRODUCTION: Melasma is one of the commonly reported pigmentory disorders in the Indian population. Numerous therapeutic modalities are available. However, very few have produced complete satisfactory response. 4-n-Butylresorcinol 0.3% cream has recently been introduced in India as a new hypopigmenting agent. It is a resorcinol derivative and acts by inhibiting both tyrosinase and tyrosinase related protein-1. OBJECTIVE: The available published literatures are with 4-n butylresorcinol 0.1% cream, and there is paucity of clinical studies with 4-n butylresorcinol 0.3% cream. Furthermore, considering the fact that Indian skin is more prone to irritation with hypopigmenting agents, our study explores the efficacy, safety, and tolerability of 4-n-butylresorcinol 0.3% cream in Indian subjects with melasma. METHODS: Fifty-two subjects with melasma participated in this open-label, single arm, observational study. All the patients were advised twice daily application of 4-n-butylresorcinol 0.3% cream for 8 weeks over the areas of melasma. Assessment parameters included modified Melasma Area Severity Index (mMASI) score. Digital photographs of all the patients at baseline, week 4, and week 8 were taken. During this 8-week study period, all the adverse events were observed and recorded. RESULTS: All the 52 subjects completed the study. Out of 52 subjects, 90.38% were females. The mean age of patients was 38.5+/-7.8 years. Mean +/- standard error of MASI score measurements showed a significant decrease from baseline score of 14.73+/-0.59 to 11.09+/-0.53 after week 4 (P<0.001) and 6.48+/-0.43 at week 8 (P<0.001). The digital photographs of the study subjects taken at week 4 and week 8 also showed decrease in melasma pigmentation compared to baseline photograph and correlated with the changes in the mMASI score. The treatment was well tolerated by all the study subjects. No adverse reactions were reported throughout the study period. CONCLUSION: Our data suggest that the 4-n-butylresorcinol 0.3% cream is safe, effective, and well tolerated in Indian patients with melasma. PMID- 26855594 TI - Pseudomonas aeruginosa ventilator-associated pneumonia management. AB - Ventilator-associated pneumonia is the most common infection in intensive care unit patients associated with high morbidity rates and elevated economic costs; Pseudomonas aeruginosa is one of the most frequent bacteria linked with this entity, with a high attributable mortality despite adequate treatment that is increased in the presence of multiresistant strains, a situation that is becoming more common in intensive care units. In this manuscript, we review the current management of ventilator-associated pneumonia due to P. aeruginosa, the most recent antipseudomonal agents, and new adjunctive therapies that are shifting the way we treat these infections. We support early initiation of broad-spectrum antipseudomonal antibiotics in present, followed by culture-guided monotherapy de escalation when susceptibilities are available. Future management should be directed at blocking virulence; the role of alternative strategies such as new antibiotics, nebulized treatments, and vaccines is promising. PMID- 26855597 TI - Initial assessment of the benefits of implementing pharmacogenetics into the medical management of patients in a long-term care facility. AB - The health care costs associated with prescription drugs are enormous, particularly in patients with polypharmacy (taking more than five prescription medications), and they continue to grow annually. The evolution of pharmacogenetics has provided clinicians with a valuable tool that allows for a smarter, more fine-tuned approach to treating patients for a number of clinical conditions. Applying a pharmacogenetics approach to the medical management of patients can provide a significant improvement to their care, result in cost savings by reducing the use of ineffective drugs, and decrease overall health care utilization. AltheaDx has begun a study to look at the benefits associated with incorporating pharmacogenetics into the medical management of patients who are on five or more medications. Applying pharmacogenetic guided PharmD recommendations across this patient population resulted in the elimination and/or replacement of one to three drugs, for 50% of the polypharmacy patient population tested, and an estimated US$621 in annual savings per patient. The initial assessment of this study shows that there is a clear opportunity for concrete health care savings solely from prescription drug management when incorporating pharmacogenetic testing. PMID- 26855598 TI - Hemoglobin levels and quality of life in patients with symptomatic chemotherapy induced anemia: the eAQUA study. AB - PURPOSE: To assess hemoglobin (Hb) outcomes and fatigue-related quality-of-life (QoL) (electronic assessment) in patients with solid tumors and symptomatic chemotherapy-induced anemia receiving cytotoxic chemotherapy and darbepoetin alfa (DA) or another erythropoiesis-stimulating agent according to European indication. METHODS: eAQUA was a Phase IV prospective observational study. The primary outcome (assessed in the primary analysis set [PAS]: patients receiving one or more DA dose who had baseline and week 9 assessments for Hb and QoL) was the proportion of patients receiving DA having both Hb increases >=1 g/dL and improved QoL between baseline and week 9. Functional Assessment of Cancer Therapy Fatigue (FACT-F) subscale scores were anchored to fatigue visual analog scale scores to determine the minimally important difference for improved QoL. Overall data/data over time are reported for the full analysis set (patients receiving one or more erythropoiesis-stimulating agent dose, n=1,158); week 9 data (ie, data relating to the primary and secondary outcomes) are reported for the PAS (n=510). Baseline and safety data are included for both the full analysis set and PAS. RESULTS: In the PAS, 69% of patients had stage IV disease and 96% were fatigued. The minimally important difference in FACT-F change score for QoL improvement was 3.5. From baseline to week 9, 32% (95% confidence interval: 28% 36%) of patients had both improved QoL and an Hb increase >=1 g/dL; proportions were similar across the most common tumor types. At week 9, 49% and 58% of patients had improved QoL or Hb increases >=1 g/dL, respectively; 70% and 76% had QoL or Hb improvements between baseline and study end, respectively. In the PAS, 16% of patients required transfusions and 32% required iron supplementation. Few patients (<1%) reported adverse drug reactions. CONCLUSION: In this study, patients with solid tumors receiving DA per European indication for symptomatic chemotherapy-induced anemia had clinically meaningful improvements in Hb and QoL. PMID- 26855599 TI - Positive predictive value and completeness of prenatally assigned International Classification of Disease-10 kidney anomaly diagnoses in the Danish National Patient Registry. AB - OBJECTIVE: Restricting studies of severe congenital malformations to live-born children may introduce substantial bias. In this study, we estimated the attendance to the second-trimester fetal malformation screening program. We also estimated the positive predictive value (PPV) of prenatally assigned International Classification of Disease-10 diagnoses recorded in the Danish National Patient Registry (DNPR) and the completeness of case registration. We used kidney anomalies as an example. METHODS: We identified the proportion of all Danish live-born children from January 1, 2007 to December 31, 2012, who were scanned during the second trimester using the DNPR and the Civil Registration System. Details of all fetuses with specific kidney anomaly diagnoses according to the DNPR were retrieved. The PPV was estimated using the nationwide Astraia database of pregnancy medical charts or traditional medical charts, as gold standard. The completeness was assessed using the total number of cases estimated by the capture-recapture method. RESULTS: Of 372,263 live born infants, 97.3% were scanned during the second trimester. We identified 172 fetuses in the DNPR. Of these, 149 had kidney anomalies according to Astraia or medical chart review, corresponding to a PPV of 87% (95% CI: 81%-91%). The estimated completeness was 43% (95% CI: 38%-49%) for the DNPR and 75% (95% CI: 70%-79%) for Astraia. CONCLUSION: Almost all live-born children were scanned during the second trimester in Denmark. However, low completeness may hamper the use of the DNPR for studies of prenatally detected severe malformations, and use of the Astraia database may preferably be considered. PMID- 26855600 TI - Clinical significance of video-urodynamic in female recurrent urinary tract infections. AB - PURPOSE: We aimed to assess the value of video-urodynamic study (VUD) in the identification of lower urinary tract voiding dysfunction in female recurrent urinary tract infections (UTIs). PATIENTS AND METHODS: A total of 54 women with recurrent UTIs who underwent VUDs between 2013 and 2015 were analyzed. They were carefully evaluated by complete history, voiding diary, physical investigation, urosonography, and VUDs. RESULTS: Neurogenic and non-neurogenic voiding dysfunctions were found in 4% and 63% of women respectively. Detrusor sphincter dyssynergia, detrusor underactivity, and a combination of both were found in 17% (nine of 54), 22% (12 of 54), and 11% (six of 54) of women, respectively. Overactive bladder syndrome was determined in 28% (15 of 54) of women. Reduction in the maximal urinary flow rate to less than 15 mL/s and post-void residual volume were revealed in 63% (34 of 54) and 54% (29 of 54) of women, respectively. Stress urinary incontinence was noticed in 39% (21 of 54) of women with a median pad usage of three pads (range: 1-15) daily. Urgency and nocturia were complaints in 54% (29 of 54) and 43% (23 of 54) of women, respectively. The median voiding frequency and nocturia episodes were 7+/-4 (1-13) and 1+/-3 (0-12), respectively. CONCLUSION: Dysfunctional voiding can encourage the formation of recurrent UTIs in the female. The VUDs are the investigation of choice to diagnose voiding dysfunction. PMID- 26855601 TI - The influence of cognition on self-management of type 2 diabetes in older people. AB - Diabetes is a growing public health issue, increasing in prevalence, eroding quality of life, and burdening health care systems. The complications of diabetes can be avoided or delayed by maintaining good glycemic control, which is achievable through self-management and, where necessary, medication. Older people with diabetes are at increased risk for cognitive impairment. This review aims to bring together current research that has investigated both cognition and diabetes self-management together. The Cumulative Index to Nursing and Allied Health (Cinahl), Excerpta Medica Database (Embase), Medical Literature Analysis and Retrieval System (Medline), and Psychological Information (PsychInfo) databases were searched. Studies were included if they featured older people with type 2 diabetes and had looked for associations between at least one distinct measure of cognition and at least one distinct measure of diabetes self-management. English language publications from the year 2000 were included. Cognitive measures of executive function, memory, and low scores on tests of global cognitive functioning showed significant correlations with multiple areas of diabetes self management, including diabetes-specific numeracy ability, diabetes knowledge, insulin adjustment skills, ability to learn to perform insulin injections, worse adherence to medications, decreased frequency of self-care activities, missed appointments, decreased frequency of diabetes monitoring, and increased inaccuracies in reporting blood glucose monitoring. The nature of the subjects studied was quite variable in terms of their disease duration, previous medical histories, associated medical comorbidities, and educational level attained prior to being diagnosed with diabetes. The majority of studies were of an associational nature and not findings confirmed by repeat testing or by the effects of an intervention, neither were the majority of studies designed to give a view or conclusion on the clinical value or implications of the research. This only allows speculation of their importance. Most studies do not separate out the influence of aging itself in altering diabetes self-care behavior. We conclude that older people with type 2 diabetes are at increased risk for cognitive dysfunction. Changes in cognition may negatively affect diabetes self-management behaviors, influencing self-care outcomes. Age and depression may exacerbate any cognitive impairment. PMID- 26855602 TI - The effectiveness of an educational intervention to improve knowledge and perceptions for reducing organophosphate pesticide exposure among Indonesian and South Australian migrant farmworkers. AB - BACKGROUND: Farmworkers are at risk of exposure to organophosphate pesticides (OPs). Improvements of knowledge and perceptions about organophosphate (OP) exposure may be of benefit for the reduction in OP exposure. PURPOSE: The purpose of this study was to examine the effectiveness of an educational intervention to improve knowledge and perceptions for reducing OP exposure among Indonesian and South Australian (SA) migrant farmworkers. METHODS: This was a quasi-experimental study. The educational intervention used a method of group communication for 30 Indonesian farmworkers and individual communication for seven SA migrant farmworkers. Knowledge and perceptions about OP exposure were measured pre intervention and 3 months after the intervention. RESULTS: Unadjusted intervention effects at follow-up showed statistically significantly improved scores of knowledge (both adverse effects of OPs and self-protection from OP exposure), perceived susceptibility, and perceived barriers among Indonesian farmworkers compared with SA migrant farmworkers. Furthermore, these four significant variables in the unadjusted model and the two other variables (perceived severity and perceived benefits) were statistically significant after being adjusted for the level of education and years working as a farmworker. In contrast, knowledge about adverse effects of OPs was the only variable that was statistically significantly improved among SA migrant farmworkers. The results of this study suggests educational interventions using a method of group communication could be more effective than using individual intervention. CONCLUSION: These improvements provide starting points to change health behavior of farmworkers, particularly to reduce OP exposure, both at the workplace and at home. PMID- 26855603 TI - The Toronto Hospital Alertness Test scale: relationship to daytime sleepiness, fatigue, and symptoms of depression and anxiety. AB - OBJECTIVE: The Toronto Hospital Alertness Test (THAT) scale was designed to measure alertness, defined as the capacity of the mind to respond appropriately to external and internal stimuli. The present study's aim is to determine normative values of alertness on the THAT and to explore the relationship among excessive daytime sleepiness, fatigue, depressive symptoms, and alertness. METHODS: Normative data were collected from 60 healthy males and females. To explore the relationship among alertness, daytime sleepiness, fatigue, depression, and anxiety, data were collected from charts of sleep clinic patients. All study subjects completed measures for fatigue, sleepiness, depressive symptoms, and anxiety. RESULTS: The average score on the THAT was 34.9+/-7.2 (range 22-50) for the control group. The cutoff score for the THAT, indicative of clinically significant reduced alertness, was determined to be <=20.5 (mean -2 SD). THAT alertness scores were found to be modestly, significantly, and negatively correlated with fatigue levels (r=-0.39, P<0.001), depressive symptoms (r=-0.53, P<0.001), and anxiety symptoms (r=-0.41, P<0.001). No correlations were found between alertness levels and daytime sleepiness. Regression analyses revealed a significant model (F=19.9, P<0.001, adjusted R (2)=0.35) with depressive symptoms (P<0.001) and fatigue (P=0.006) emerging as the only significant predictors of scores on the THAT. CONCLUSION: The findings of this study support that sleepiness is not the same as poor alertness. Depressive symptoms and fatigue, but not sleepiness, were found to have a strong and significant impact on levels of alertness. This is the first study to link poor alertness to depressive symptoms. PMID- 26855604 TI - Volatile organic compound conversion by ozone, hydroxyl radicals, and nitrate radicals in residential indoor air: Magnitudes and impacts of oxidant sources. AB - Indoor chemistry may be initiated by reactions of ozone (O3), the hydroxyl radical (OH), or the nitrate radical (NO3) with volatile organic compounds (VOC). The principal indoor source of O3 is air exchange, while OH and NO3 formation are considered as primarily from O3 reactions with alkenes and nitrogen dioxide (NO2), respectively. Herein, we used time-averaged models for residences to predict O3, OH, and NO3 concentrations and their impacts on conversion of typical residential VOC profiles, within a Monte Carlo framework that varied inputs probabilistically. We accounted for established oxidant sources, as well as explored the importance of two newly realized indoor sources: (i) the photolysis of nitrous acid (HONO) indoors to generate OH and (ii) the reaction of stabilized Criegee intermediates (SCI) with NO2 to generate NO3. We found total VOC conversion to be dominated by reactions both with O3, which almost solely reacted with d-limonene, and also with OH, which reacted with d-limonene, other terpenes, alcohols, aldehydes, and aromatics. VOC oxidation rates increased with air exchange, outdoor O3, NO2 and d-limonene sources, and indoor photolysis rates; and they decreased with O3 deposition and nitric oxide (NO) sources. Photolysis was a strong OH formation mechanism for high NO, NO2, and HONO settings, but SCI/NO2 reactions weakly generated NO3 except for only a few cases. PMID- 26855605 TI - Charm and beauty quark masses in the MMHT2014 global PDF analysis. AB - We investigate the variation in the MMHT2014 PDFs when we allow the heavy-quark masses [Formula: see text] and [Formula: see text] to vary away from their default values. We make PDF sets available in steps of [Formula: see text] and [Formula: see text], and present the variation in the PDFs and in the predictions. We examine the comparison to the HERA data on charm and beauty structure functions and note that in each case the heavy-quark data, and the inclusive data, have a slight preference for lower masses than our default values. We provide PDF sets with three and four active quark flavours, as well as the standard value of five flavours. We use the pole mass definition of the quark masses, as in the default MMHT2014 analysis, but briefly comment on the [Formula: see text] definition. PMID- 26855608 TI - Sleep medicine in Taiwan. AB - The sleep medicine is a young medical science in Taiwan. It began from less than 10 sleep beds 20 years ago in four hospitals all over Taiwan. By the organization of sleep team in Chang Gung Memorial Hospital and the initiation of Taiwan Society of Sleep Medicine, sleep medicine becomes a popular medicine in the past decades. The setting of Sleep Society in 2002 is the milestone to promote the sleep medicine, educate the public and professionals, and control of the quality of clinical practice. Epidemiologic study in Taiwan shows many Taiwanese suffer from sleep disorders and hence more sleep institutes are needed. Accreditation has become a mission of the Taiwan Society of Sleep Medicine. Technicians, sleep centers, sleep specialists and sleep phycologists are gradually certified by the society. 215 sleep technicians, 307 sleep physicians, 31 iCBT therapists and 21 sleep centers are certified by the society till 2015. The first sleep related medical courses are initiated in the Department of Respiratory Therapy in Chang Gung University from 2003. For the following years, eight medical courses are set in six Universities now. Given the fact that the Asian accounts for the largest proportion of population in the world, investigation on the OSA in Asian population is essential. In this article, we aimed to demonstrate the outcomes of OSA-related research in Asia. In particular, the progress driven by the studies in Taiwan will be discussed. Data were obtained online from the Science Citation Index Expanded database of the Thomson Reuters' Web of Science Core Collection. Keywords including "apnea" and "hyponea" were used to search by applying the filters of the title and the publication years between 1991 and 2014. In total, 2623 articles were hit, subject to the criteria for data search. Among the 2623 articles, sleep and breathing related articles (128, 4.95 %) were the most frequently reported. Japan is the country that published the highest amount of OSA-related articles. The Asian institutions that ranked the first two in the number of OSA-related articles were Technion-Israel Institute of Technology and Tel Aviv University in Israel. In Taiwan, Chang Gung Memorial Hospital and Chang Gung University ranked fourth and fifth. Both institutes reported 63 articles. In Asia, Japan leads in the quantity of publication and the Japanese research institutes performed evenly. China had rapid growth in the number of articles since 2011. Although sleep medicine developed smoothly in the past decades in Taiwan, there were problems that the sleep society and specialists had to encounter. Insurance limits the expansion of sleep labs and the reimbursement is very low for sleep medicine to survive. The affiliations of sleep specialist and the sleep education are also important issue that the sleep specialists in the society have to discuss.The previous achievements do not guarantee future success. We have to face these problems seriously and take action for the following years to maintain the development of sleep medicine in Taiwan. PMID- 26855609 TI - "Non-dipping" is equally frequent in narcoleptic patients and in patients with insomnia. AB - Narcolepsy with cataplexy (NC) is a neurological sleep disorder characterized by very low or undetectable concentration of hypocretin-1 in the cerebrospinal fluid. It has been recently found that patients with NC have disturbed circadian pattern of blood pressure, with more frequent non-dipping, compared to healthy controls. It has been hypothesized that lack of hypocretin may lead to increase in nocturnal blood pressure. This increase may result also from disturbed sleep architecture regardless of the deficiency of hypocretin. The aim of this study was to compare changes in values of daytime and nighttime blood pressure in NC patients and in patients with disturbed nocturnal sleep due to other sleep disorders. We have retrospectively compared polysomnographic and clinical data of 8 NC patients and 7 age- and sex controls suffering from insomnia. We have compared sleep architecture, mean blood pressure values and dipping pattern in both groups. The groups did not differ in terms of disturbances of sleep architecture. We have not found any statistical differences in values of daytime and nocturnal blood pressure. Non-dipping was equally frequent in both groups (87.5 and 85.7 %). Our results suggest that observed abnormalities in circadian changes of blood pressure values result from disturbed sleep architecture than from deficiency of hypocretin. Patients with sleep disorders should be carefully observed for the presence of increased blood pressure and other vascular risk factors. PMID- 26855610 TI - Sleep education with self-help treatment and sleep health promotion for mental and physical wellness in Japan. AB - The purpose of this article was to provide an overview of the effects of the sleep education with self-help treatment for student, teacher, and local resident and sleep health promotion for mental and physical wellness for elderly with actual examples of public health from the community and schools. Sleep education with self-help treatment in schools revealed that delayed or irregular sleep/wake patterns were significantly improved. Also, it was effective for improving sleep onset latency, sleep satisfaction, mood during the morning, and daytime sleepiness. The strategy of this sleep education included the acquisition of the correct knowledge about sleep and the sleep-related behaviors that are important for improving sleep. Sleep health promotion that included short naps and exercise in the evening (Sleep health class) was effective in promoting sleep and mental health with elderly people. The interventions demonstrated that the proper awakening maintenance, keeping proper arousal level during the evening was effective in improving sleep quality. Furthermore, sleep management that included sleep education and cognitive-behavioral interventions improved sleep-related habits and the quality of sleep. In this study, a sleep educational program using minimal cognitive-behavioral modification techniques was developed. Mental and physical health was also improved with better sleep in the elderly. These results suggest that sleep health promotion is effective for mental and physical wellness for the elderly. PMID- 26855611 TI - Change in Chirality of Semiconducting Single-Walled Carbon Nanotubes Can Overcome Anionic Surfactant Stabilization: A Systematic Study of Aggregation Kinetics. AB - Single-walled carbon nanotubes' (SWNT) effectiveness in applications is enhanced by debundling or stabilization. Anionic surfactants are known to effectively stabilize SWNTs. However, the role of specific chirality on surfactant-stabilized SWNT aggregation has not been studied to date. The aggregation behavior of chirally enriched (6,5) and (7,6) semiconducting SWNTs, functionalized with three anionic surfactants-sodium dodecyl sulfate (SDS), sodium dodecyl benzene sulfonate (SDBS), and sodium deoxycholate (SDOCO)-was evaluated with time resolved dynamic light scattering. A wide range of mono- (NaCl) and di-valent (CaCl2) electrolytes as well as a 2.5 mg TOC/L Suwannee River humic acid (SRHA) were used as background chemistry. Overall, SDBS showed the most effectiveness in SWNT stability, followed by SDOCO and SDS. However, the relatively larger diameter (7,6) chiral tubes compromised the surfactant stability, compared to (6,5) chiral enrichment, due to enhanced van der Waals interaction. The presence of di-valent electrolytes overshadowed the chirality effects and resulted in similar aggregation behavior for both the SWNT samples. Molecular modeling results enumerated key differences in surfactant conformation on SWNT surfaces and identified interaction energy changes between the two chiralities to delineate aggregation mechanisms. The stability of SWNTs increased in the presence of SRHA under 10 mM monovalent and mixed electrolyte conditions. The results suggest that change in chirality can overcome surfactant stabilization of semiconducting SWNTs. SWNT stability can also be strongly influenced by the anionic surfactant structure. PMID- 26855613 TI - Health-related quality of life and nursing-sensitive outcomes in mechanically ventilated patients in an Intensive Care Unit: a study protocol. AB - BACKGROUND: Mechanical ventilation (MV) is one of the most utilised techniques in the intensive care unit (ICU), but it can cause sequelae that can negatively influence the patient's health-related quality of life (HRQL). Nursing-sensitive outcomes (NSOs) can also influence the HRQL. Assessing the HRQL of mechanically ventilated patients admitted to an ICU and its relation to nurse-sensitive outcomes will give healthcare professionals with valuable information to improve patient care. METHODS: Prospective longitudinal cohort study in which all patients admitted to the ICU at Hospital Universitari Vall d'Hebron who undergo MV for more than 48 h will be included. The study will last 12 consecutive months. HRQL will be assessed by the completion of the SF-36 and the Saint Georges Respiratory Questionnaire. Pre-admission HRQL assessment will be performed by the main caregiver, and after ICU discharge, the assessment will be performed by the patient him/herself. The same questionnaires will also be completed one year after ICU discharge. Other variables (sociodemographic and those related to reason for ICU admission, ICU length of stay, MV, ICU stressors and NSO) will be included in a multiple regression model to assess their relation to the patient's HRQL. DISCUSSION: This study will show the relationship between the HRQL perceived by patients and their main caregiver, what the HRQL is one year after discharge from ICU, and what the impact of MV, NSO and ICU stressors and other clinical outcomes on the patient's HRQL is. Determining mechanically ventilated patients' HRQL and its relation to NSO and ICU stressors as well as other clinical variables will enable early nursing interventions to try to minimise possible sequelae and improve the patient's welfare. TRIAL REGISTRATION: ClinicalTrials.gov ID:NCT02636660Registration Date: 17th December 2015. PMID- 26855612 TI - 'I try not to bother the residents too much' - the use of capillary blood glucose measurements in nursing homes. AB - BACKGROUND: Capillary blood glucose measurements are regularly used for nursing home residents with diabetes. The usefulness of these measurements relies on clear indications for use, correct measurement techniques, proper documentation and clinical use of the resulting blood glucose values. The use of a regular, invasive procedure may also entail additional challenges in a population of older, multimorbid patients who often suffer from cognitive impairment or dementia. The aim of this study was to explore the perspectives of physicians, registered nurses and auxiliary nurses on the use, usefulness and potential challenges of using capillary blood glucose measurements in nursing homes, and the procedures for doing so. METHODS: This was a qualitative study that used three profession-specific focus group interviews. Interviews were transcribed in modified verbatim form and analysed in accordance with Malterud's principles of systematic text condensation. Five physicians, four registered nurses and three auxiliary nurses participated in the focus groups. RESULTS: All professional groups regarded capillary blood glucose measurements as a necessity in the management of diabetes, the physicians to ensure that the treatment is appropriate, and the nurses to be certain and assured about their caring decisions. Strict glycaemic control and excessive measurements were avoided in order to promote the well-being and safety of the residents. Sufficient knowledge of diabetes symptoms, equivalent practices for glucose measurement, and unambiguous documentation and communication of results were determined to be most helpful. However, all professional groups seldom involved the residents in managing their own measurements and stated that guidelines and training had been inconsistent or lacking. CONCLUSION: Inadequate procedures and training in diabetes care may compromise the rationale for capillary blood glucose measurements in nursing homes, and hence the residents' safety. These concerns should be addressed together with the possibility of involving and empowering residents by exploring their ability and wish to manage their own disease. PMID- 26855614 TI - Role of goblet cell protein CLCA1 in murine DSS colitis. AB - BACKGROUND: The secreted goblet cell protein CLCA1 (chloride channel regulator, calcium-activated-1) is, in addition to its established role in epithelial chloride conductance regulation, thought to act as a multifunctional signaling protein, including cellular differentiation pathways and induction of mucus production. Specifically, CLCA1 has recently been shown to modulate early immune responses by regulation of cytokines. Here, we analyze the role of CLCA1, which is highly expressed and secreted by colon goblet cells, in the course of murine dextran sodium sulfate-induced colitis. FINDINGS: We compared Clca1-deficient and wild type mice under unchallenged and DSS-challenged conditions at various time points, including weight loss, colon weight-length-ratio and histological characterization of inflammation and regeneration. Expression levels of relevant cytokines, trefoil factor 3 and E-cadherin were assessed via quantitative PCR and cytometric bead arrays. Lack of CLCA1 was associated with a more than two-fold increased expression of Cxcl-1- and Il-17-mRNA during DSS colitis. However, no differences were found between Clca1-deficient and wild type mice under unchallenged or DSS-challenged conditions in terms of clinical findings, disease progression, colitis outcome, epithelial defects or regeneration. CONCLUSIONS: CLCA1 is involved in the modulation of cytokine responses in the colon, albeit differently than what had been observed in the lungs. Obviously, the pathways involved depend on the type of challenge, time point or tissue environment. PMID- 26855615 TI - Law as a tool to promote healthcare safety. AB - PURPOSE: The purpose of this paper is to inform healthcare providers and healthcare facility leadership about the statutory, administrative, criminal, and tort law implications related to preventable harms from unsafe injection practices. DESIGN/METHODOLOGY/APPROACH: Review of legal theory and precedents. FINDINGS: The law can address disputes over unsafe injection practices in a variety of ways. Administrative agencies may hold a provider or facility responsible for preventable harms according to specific statutory and regulatory provisions governing licensure. State courts can compensate victims of certain actions or inactions based on tort law, where a breach of a legal duty caused damages. Prosecutors and the public can turn to criminal law to punish defendants and deter future actions that result in disability or death. RESEARCH LIMITATIONS/IMPLICATIONS: The state law findings in this review are limited to legal provisions and court cases that are available on searchable databases. Due to the nature of this topic, many cases are settled out of court, and those records are sealed from the public and not available for review. PRACTICAL IMPLICATIONS: Preventable harm continues to occur from unsafe injection practices. These practices pose a significant risk of disease or even death for patients and could result in legal repercussions for healthcare providers and facility leadership. ORIGINALITY/VALUE: This article reviews emerging law and potential legal implications for health care and public health related to unsafe medical practices related to needle, syringe, and vial use. PMID- 26855616 TI - Psychopathy, intelligence and emotional responding in a non-forensic sample: an experimental investigation. AB - This study examined the relationships between psychopathy (primary and secondary), intelligence and emotional responding in a sample of 50 university students, using a task measuring autonomic responses to 40 pictorial stimuli (20 neutral and 20 emotionally provoking). Results indicated no significant direct relationship between primary or secondary psychopathy and emotional response, or primary or secondary psychopathy and intelligence. However, a significant moderating effect of intelligence on the association between both psychopathy factors and emotional response was observed, indicating those scoring higher on psychopathy but with lower intelligence portray the expected emotional responses to the affective stimuli (primary: beta = -.56, p < .05; secondary: beta = .80, p < .001). These findings indicate abnormal reactivity to emotional stimuli in lower intelligence, higher psychopathic individuals, and suggest differing roles for the two facets of psychopathy in affective responsiveness deviations. PMID- 26855618 TI - Perceptions of Parenting Practices as Predictors of Aggression in a Low-Income, Urban, Predominately African American Middle School Sample. AB - This research examined the relation between early adolescent aggression and parenting practices in an urban, predominately African American sample. Sixth graders (N = 209) completed questionnaires about their overt and relational aggressive behaviors and perceptions of caregivers' parenting practices. Findings indicated that moderate levels of parental expectations for peaceful solutions at Time 1 were associated with a lower likelihood of overt aggression at Time 2. Furthermore, findings suggest that when caregivers' support and knowledge of adolescents' whereabouts were relatively low or when caregivers' exerted high psychological control, moderate levels of parental expectations for peaceful solutions protected early adolescents against engagement in both overt and relational aggression. The implications of the findings for schools and other youth violence prevention settings are discussed. PMID- 26855619 TI - A Potential Crack in our Experience with Bisphosphonate Therapy. PMID- 26855617 TI - Sexual Health Knowledge in a Sample of Perinatally HIV-infected and Perinatally exposed Uninfected Youth. AB - This study describes sexual health knowledge in perinatally HIV-infected (PHIV+) and perinatally-exposed uninfected (PHIV-) ethnic-minority youth, ages 9-16 years, residing in NYC (n=316). Data on youth sexual health knowledge (e.g., pregnancy, STDs, birth control) and caregiver-adolescent communication about sexual health were examined. Participants in both groups answered only 35% of the sexual health knowledge questions correctly (mean=6.6/19). Higher scores were found among youth who reported more communication about sex with caregivers (vs. those who did not report talking about sex with caregivers; 8.54 vs. 5.84, p<.001) and among PHIV+ youth who were aware of their status (vs. PHIV+ youth who were not; 7.27 vs. 4.70, p<.001). Age was positively correlated with sexual health knowledge (beta=.489, p<.001). Both PHIV+ and PHIV- youth had poor sexual health knowledge, suggesting a need for sexual health education for both groups. Data suggest that interventions focused on caregiver-child risk communication may be important for prevention. PMID- 26855620 TI - Useful Functional Outcome Can Be Achieved After Motor Nerve Transfers in Management of the Paralytic Hand. An Observational Study. AB - BACKGROUND: Nerve transfers have demonstrated encouraging outcomes in peripheral nerve reconstructions compared with the conventional direct repair or grafting. QUESTIONS/PURPOSES: We aimed to identify whether the patient's demographics, delay to surgery, degree of loss of grip and pinch strengths, mechanism of injury, and compliance to hand therapy have an impact on the functional outcome of motor nerve transfers in patients with paralytic hand. METHODS: Fifty-five patients with a mean age of 31.05 (18-48) years with complete isolated high injuries of radial, ulnar, and median nerves, who underwent motor nerve transfers, were reviewed. The outcome was assessed using the Medical Research Council (MRC) scale and measurement of grip and pinch strengths of the hand at minimum 1-year follow-up (mean of 14.4 (12-18) months). Patient's age and gender, delay to surgery, body mass index (BMI), degree of loss of grip and pinch strengths, educational level, occupation, mechanism of injury, and compliance to hand therapy were analyzed to determine their impact on the extent of recovery of hand function. RESULTS: Forty of fifty five (72.73%) patients regained useful functional recovery (M3-M4) with satisfactory grip hand functions. Worse motor recovery was observed in older ages, delayed surgical intervention, higher BMI, and greater postoperative loss of grip and pinch strengths in comparison to the healthy opposite hand. Better outcomes are significantly associated with higher educational level and postoperative compliance to hand therapy. Contrarily, there was no significant association between gender, occupation, mechanism of injury, and achievement of useful functional recovery. CONCLUSIONS: Successful nerve transfers are expected with experienced skilled surgeons. However, outstanding outcomes are not the standard, with about one fourth failing to achieve M3 grade. The educational level, hand dominance, compliance to hand therapy, loss of grip and pinch strengths, age, injury-surgery interval, and BMI are possible predictors of patients' outcome. PMID- 26855621 TI - Humeral Tray-Taper Failure in Modular Reverse Total Shoulder Arthroplasty. AB - BACKGROUND: Reverse total shoulder arthroplasty (RTSA) provides reconstructive options in patients previously not candidates for total shoulder arthroplasty (TSA) or who have failed previous anatomic TSA. Revision from anatomic TSA to RTSA previously required removal of all components, a difficult and extensive procedure. Modular humeral components permit conversion from anatomic TSA to RTSA without removal of well-fixed humeral components. QUESTIONS/PURPOSES: Our purpose is to present a case series of patients treated for the unique and not previously reported complication of humeral tray-taper failure following modular RTSA. Challenges in diagnosis and treatment are described, including the use of dynamic fluoroscopy and manufacturer-specific instruments for component revision. METHODS: Five patients with a total of six humeral tray-taper failures were identified from 300 patients with first-generation (titanium) humeral trays over a 7-year period. Dynamic fluoroscopic evaluation aided in diagnosis in a majority of the cases. All cases have been revised to second-generation (cobalt chrome) humeral trays. RESULTS: Average follow-up was 22 +/- 23 months (range 3-60 months). One individual required a second revision for the same complication, but otherwise, no additional procedures were required. Symptom relief was obtained in all patients. CONCLUSIONS: This case series illustrates a previously unpublished complication of humeral tray-taper junction failure following modular RTSA. Clinical and radiographic diagnosis is challenging; however, dynamic fluoroscopic evaluation permits identification of the component failure, and revision surgery results in good outcomes. We must, however, continue to evaluate what activities are recommend for patients following shoulder arthroplasty, specifically reverse total shoulder arthroplasty. PMID- 26855622 TI - Initial Surgical Treatment of Humeral Shaft Fracture Predicts Difficulty Healing when Humeral Shaft Nonunion Occurs. AB - BACKGROUND: Although most humeral nonunions are successfully treated with a single procedure, some humeral nonunions are more difficult to heal and require multiple procedures. Current literature does not provide evidence describing how the prognosis for surgical repair in patients who develop humeral diaphyseal nonunions may be affected by initial operative versus nonoperative treatment. QUESTIONS/PURPOSES: The purpose of this study was to assess whether operative versus nonoperative treatment of acute humeral shaft fractures impacts outcome of subsequent repairs of humeral nonunions (NU) including the need for additional surgery and a comparison of pain relief (Visual Analogue Scale for pain) and functional outcome (Short Musculoskeletal Functional Assessment). METHODS: Thirty four patients with humeral shaft nonunion were evaluated of which 15 patients had been treated operatively (OF), and 19 patients had been treated nonoperatively (NO) for their initial humerus shaft fracture. All patients underwent plating with autogenous bone graft or allograft +/- bone morphogenic protein (BMP) 2 or 7 as their final NU repair surgery prior to healing. We compared functional outcome and pain for both cohorts and determined risk factors for requiring more than 1 nonunion repair surgery. RESULTS: The mean time of final follow-up was 14.7 +/- 10.4 months. Thirty-three of 34 NUs (97.1%) healed. Patients who underwent OF of their original fracture were more likely to require more than 1 NU repair surgery (66.7 vs. 0%, p < 0.01). Of the 15 patients who underwent initial OF, 33.0% required 1 NU surgery, 33.0% required 2 NU surgeries, and 33.0% required 3 NU surgeries. Patients who underwent initial OF were more likely to require >6 months to achieve union (40.0 vs. 10.5%, p = 0.04). At final follow-up, there was no difference in functional outcome or pain scores. Initial OF was the only independent predictor of needing more than 1 NU repair surgery (OR 70.1 CI 2.8 1762.3) to achieve healing. CONCLUSION: Humeral shaft nonunions following initial operative fixation of the index fracture is more resistant to achieving union when compared to nonunions forming after initial nonoperative treatment. When final healing is achieved, there is no difference in function or pain. PMID- 26855623 TI - Maintenance of Derotation in Adolescent Idiopathic Scoliosis: a Novel Technique Measuring Postoperative Vertebral Rotation by Pedicle Screw Position. AB - BACKGROUND: Current methods of measuring vertebral rotation by plain radiographs rely on anatomic landmarks that are not present in the postoperative spine or require advanced imaging. Furthermore, there are few studies on the incidence of crankshaft with modern pedicle instrumentation. QUESTIONS/PURPOSES: We sought to (1) describe and validate a method of vertebral rotation measurement using plain radiographs and (2) measure postoperative rotation in a series of patients treated for adolescent idiopathic scoliosis. METHODS: Patients with adolescent idiopathic scoliosis treated with surgery over a 6-year period were reviewed. Patients with computed tomography (CT) scans and radiographs within 60 days of another were included. Vertebral rotation was calculated by radiographic measurements and measured directly by CT scan. As an internal control, patients with two apical pedicle screws on all radiographs were analyzed. Rotation was measured for all patients with at least 1 year of radiographic follow-up. RESULTS: Three thousand five hundred fifty-two instrumented spinal levels in 308 consecutive patients were reviewed. Ten patients with 93 screws were analyzed by CT and radiographs. The average discrepancy between computed tomography (CT) and radiographs was 3.3 +/- 1.9 degrees , with 81.7% (76/93) within 5 degrees . Intra and inter-rater reliabilities for measured axial rotation were excellent (intra class correlation coefficient (ICC) = 0.879 and 0.900, respectively). One hundred swventy-eight patients were eligible with an average follow-up of 2.3 +/- 1.2 years; 84.8% (151/178) had screw(s) visible on all images at the major curve apex. The average postsurgical rotation was 3.5 +/- 2.9 degrees ; 19.2% (29/151) were measured to have a rotation over 5 degrees , and 4.0% (6/151) demonstrated a rotation over 10 degrees . Only 4.6% (7/151) of patients demonstrated a postoperative Cobb angle change over 10 degrees . CONCLUSIONS: Most major curves have apical pedicle screw instrumentation that can be followed by radiographs alone to measure rotation. Vertebral rotation measurement requires only plain radiographs and is a more sensitive determination for subtle postoperative crankshaft than change in Cobb angle. PMID- 26855624 TI - Young Females Exhibit Decreased Coronal Plane Postural Stability Compared to Young Males. AB - BACKGROUND: Female athletes are at significantly higher risk of noncontact ACL injury than males, particularly in pivoting sports such as soccer and basketball. Sex-based differences in proprioception and core stability may contribute to this elevated risk. QUESTIONS/PURPOSE: This study evaluates a novel method of assessing dynamic stability to test the hypothesis that healthy adolescent controls have sex-based differences in postural stability. METHODS: Seventy-nine male and 72 female subjects completed three rounds of dynamic postural stability testing. During the assessment, subjects attempted to stabilize their torso and upper body in response to random movements of the platform. The total time a subject lasted on the platform and dynamic motion analysis (DMA) score, a summation of motion in five planes throughout testing, was calculated for each subject. The average score for each subject was included in the analysis. RESULTS: Males lasted longer on the platform (98 +/- 14 s) than females (94 +/- 13 s) (p = 0.04). Coronal plane and rotation stability differed significantly between genders (323 +/- 126 vs. 365 +/- 128, p = 0.04) and (318 +/- 82 vs. 403 +/- 153, p = 0.0002), respectively. No statistically significant difference was seen in the other planes of motion. CONCLUSIONS: Females have less dynamic postural stability than their male counterparts in the coronal plane based on a novel assessment tool. This finding may contribute to better understanding of sex based differences in rates of injury such as noncontact ACL tears. PMID- 26855625 TI - Anteroposterior Radiographs Are More Accurate than Cross-Table Lateral Radiographs for Acetabular Anteversion Assessment: a Retrospective Cohort Study. AB - BACKGROUND: Measuring acetabular anteversion is relevant to routine follow-up of total hip arthroplasties (THAs) and for malfunctioning THAs. Imageless navigation facilitates acetabular component orientation relative to the anterior pelvic plane (APP) or to the APP adjusted for sagittal pelvic tilt (PT). The optimal plain radiographic method for the postoperative assessment of anteversion is not agreed upon. QUESTIONS/PURPOSES: (1) Do anteversion measurements on plain radiographs correlate more with APP anteversion or PT-adjusted anteversion? (2) Do measurements of anteversion performed on supine anteroposterior (AP) radiographs more accurately reflect intraoperative anteversion values for navigated THA compared to anteversion measured on cross-table lateral (CL) radiographs? METHODS: Seventy patients receiving primary navigated THA were included. APP and PT-adjusted anteversion were recorded; the latter defined the intraoperative target for anteversion. Postoperative anteversion was measured on supine AP pelvis radiographs with computer software and CL radiographs with conventional methods. Intraoperative measurements were used as the reference standards for comparisons. RESULTS: Mean intraoperative APP anteversion was 20.6 degrees +/- 5.6 degrees . Mean intraoperative PT-adjusted anteversion was 22.9 degrees +/- 4.5 degrees . Mean anteversion was 22.7 degrees +/- 4.7 degrees on AP radiographs and 27.2 degrees +/- 4.2 degrees on CL radiographs (p < 0.001). Only correlations between PT-adjusted anteversion and radiographic assessments of anteversion were significant. The mean difference between PT-adjusted anteversion and anteversion on AP radiographs was -0.2 degrees +/- 4.3 degrees , while the mean difference between the PT-adjusted anteversion and anteversion measured on CL radiographs was 4.3 +/- 5.1 degrees (p < 0.001). CONCLUSION: Plain film assessment of anteversion was more accurate on supine AP radiographs than on CL radiographs, which overestimated acetabular anteversion. PMID- 26855626 TI - Simulated Ankle Equinus Affects Knee Kinematics During Gait. AB - BACKGROUND: It is critical to distinguish gait compensations from true abnormalities when planning interventions to improve gait in individuals with neuromuscular disorders. QUESTIONS/PURPOSES: The aim of this study was to determine the effect of isolated ankle equinus on knee kinematics during the initial contact phase of gait. METHODS: Ten healthy subjects (29 + 4.3 years) participated, and testing occurred in a motion analysis laboratory. This cross sectional study investigated five gait conditions in each subject: shoe alone, shoe with unilateral ankle foot orthosis locked at neutral, 10 degrees , 20 degrees , and 30 degrees of fixed ankle plantar flexion. Gait kinematics were recorded and calculated with 3D motion analysis. The difference between the shoe and each brace condition was analyzed by repeated-measures ANOVA. The primary outcome was knee flexion at initial contact. RESULTS: With greater than 10 degrees simulated ankle equinus, the primary gait compensation pattern was increased knee flexion at initial contact. A significant degree of knee flexion occurred ranging from 7 degrees to 22 degrees . CONCLUSION: Our data suggests that observed knee flexion at initial contact may be a compensation pattern in individuals with >10 degrees ankle equinus. However, in individuals with <=10 degrees ankle equinus, observed knee flexion may represent a true gait deviation. This has clinical significance in the realm of cerebral palsy for treatment planning to improve gait. PMID- 26855627 TI - Validation of the Foot and Ankle Outcome Score for Hallux Rigidus. AB - BACKGROUND: There is a clear call for improved patient-centered outcomes. The Foot and Ankle Outcome Score (FAOS) is a region-specific patient-reported measure that has been validated for a number of foot and ankle diagnoses, but not hallux rigidus. QUESTIONS/PURPOSES: The aim of this study was to validate the FAOS in patients with hallux rigidus. METHODS: From 2007 to 2013, 211 patients with hallux rigidus (HR) were included in the study. For the construct validity portion of the study, 125 patients completed a Short-Form 12 (SF-12) and FAOS survey. Forty additional HR patients were prospectively given questionnaires to assess the relevance of each FAOS question as it pertained to their HR. Reliability was assessed in 36 HR patients via administration of a second FAOS an average 1 month following the first. In 55 patients, preoperative and postoperative FAOS scores were compared to determine responsiveness. RESULTS: All FAOS subscales demonstrated moderate correlation coefficients with the physical functioning, role physical, bodily pain, and physical health component scores of the SF-12, with all subscales demonstrating poor correlation with the SF-12 mental health-related domains. Content validity was high for all FAOS scores, with the exception of the daily activities subscale. All subscales achieved acceptable test-retest reliability with correlation coefficients of >=0.72. Furthermore, all subscales were rated as responsive to change in postoperative patients (p < 0.001). CONCLUSION: This study demonstrates the acceptable construct and content validity, reliability, and responsiveness of the FAOS for hallux rigidus. Due to its broad applicability and proven validation across multiple foot and ankle pathologies, the FAOS represents a patient-centered outcome measure that can be reliably used for the assessment of patients with hallux rigidus. PMID- 26855628 TI - Assessment of Osteonecrosis in the Presence of Instrumentation for Femoral Neck Fracture Using Contrast-Enhanced MAVRIC Sequence. AB - BACKGROUND: Evaluating postoperative femoral neck facture (FNF) with metal fixation hardware is commonly performed using radiographs. MRI has greater sensitivity and specificity to evaluate osteonecrosis (ON) but is often challenging due to the image distortion caused by metallic hardware. QUESTIONS/PURPOSES: The aim of this study is to compare fast spin-echo (FSE) and multi-acquisition variable-resonance image combination (MAVRIC) sequences in assessing ON following metallic fixation of FNF and determining feasibility of semi-quantitative perfusion using MAVRIC. METHODS: Radiography and MRI were performed at 3 and 12 months postoperatively, using FSE and pre- and post gadolinium contrast MAVRIC sequences in 21 FNF patients. The presence and volume of ON were recorded. Signal intensity (SI) enhancement was measured on the MAVRIC sequences within the center and rim of ON; with the ilium and femoral diaphysis as controls. The detection rate of ON between MAVRIC and FSE images was evaluated as the difference of percent enhancement across the defined regions of interest. RESULTS: ON was detected in 0% of radiographs, in 67% of FSE, and in 76% of MAVRIC images at 3 months follow-up, with similar results at 12 months. MAVRIC images had larger ON volume than FSE images at both time points. A significant percentage SI enhancement was only detected in the ON rim. CONCLUSION: Radiographs could not detect ON following metallic fixation of FNF. MAVRIC is more sensitive than FSE for determining the volume of ON. SI measurements using MAVRIC may provide an indirect assessment of perfusion. PMID- 26855629 TI - The Need for a Step-up in Postoperative Medical Care is Predictable in Orthopedic Patients Undergoing Elective Surgery. AB - BACKGROUND: The goal of elective orthopedic surgery is to return patients to their expected level of activity without an increased incidence of postoperative complications. The first step is identifying patient and/or surgical characteristics responsible for these complications. QUESTIONS/PURPOSES: This study sought to identify predictors of a step-up in medical care after non ambulatory elective orthopedic surgery. METHODS: At a single specialty orthopedic hospital, we identified all in-hospital postoperative patients who were transferred to a higher level of medical care ((PACU) post-anesthesia care unit). The characteristics of both transferred and non-transferred patients were compared. A model was built which incorporated predictors of return to a higher level of care. RESULTS: During a 1-year period, 155 of 7967 patients (1.95%) required transfer to the PACU within 5 days of surgery. Cardiac complications were the major reason for transfer (50.3%), followed by pulmonary (11.0%) and neurological complications (9.7%). Patients who returned to the PACU were older, had more Exlihauser comorbidities, and had obstructive sleep apnea (OSA). In a model adjusting for all patient characteristics: age, American Society of Anesthesiologists (ASA) status, congestive heart failure (CHF), the Charlson comorbidity index and OSA predicted return to the PACU. CONCLUSIONS: In an elderly population with multiple comorbidities undergoing elective common major orthopedic procedures, approximately 2% of patients required readmission to the PACU. The most common problems requiring this step-up in care were cardiac and pulmonary, which resulted in an increased length of hospital stay. Patients with OSA and multiple comorbidities undergoing total knee arthroplasty carry an increased risk for postoperative complications. PMID- 26855631 TI - Bisphosphonate Drug Holiday? Celebrate?: Commentary on article by Jordan C. Villa, MD, Arianna Gianakos, BS, Jospeh M. Lane, MD Bisphosphonate Treatment in Osteoporosis: Optimal Duration of Therapy and the Incorporation of a Drug Holiday. PMID- 26855630 TI - Bisphosphonate Treatment in Osteoporosis: Optimal Duration of Therapy and the Incorporation of a Drug Holiday. AB - BACKGROUND: Bisphosphonates are the most widely used treatment for osteoporosis. They accumulate in the bone for years, and therefore, their inhibitory effects on osteoclasts may persist after drug discontinuation. The ideal duration of therapy remains controversial. QUESTIONS/PURPOSES: The purpose of this study is to review the literature to determine the (1) indications for drug holiday, (2) the duration of drug holiday, (3) the evaluation during drug holiday, and (4) the proper treatment and maintenance after drug holiday. METHODS: A review of two electronic databases (PubMed/MEDLINE and EMBASE) was conducted using the term "(Drug holiday)," in January 29, 2015. Inclusion criteria were as follows: (1) clinical trials and case control, (2) human studies, (3) published in a peer review journal, and (4) written in English. Exclusion criteria were as follows: (1) case reports, (2) case series, and (3) in vitro studies. RESULTS: The literature supports a therapeutic pause after 3-5 years of bisphosphonate treatment in patients with minor bone deficiencies and no recent fragility fracture (low risk) and in patients with moderate bone deficiencies and/or recent fragility fracture (moderate risk). In these patients, a bone health reevaluation is recommended every 1-3 years. Patients with high fracture risk should be maintained on bisphosphonate therapy without drug holiday. CONCLUSION: The duration and length of drug holiday should be individualized for each patient. Evaluation should be based on serial bone mass measurements, bone turnover rates, and fracture history evaluation. If after drug therapy, assessments show an increased risk of fracture, the patient may benefit from initiating another treatment. Raloxifene, teriparatide, or denosumab are available options. PMID- 26855632 TI - The Distribution of Ochronosis in Osteoarthritic Articular Cartilage in a Knee. PMID- 26855633 TI - Pulmonary Embolism in a Baseball Pitcher Following Open Shoulder Capsular Repair. PMID- 26855634 TI - Lengthening of Tibia after Trans-Tibial Amputation: Use of a Weight Bearing External Fixator-Prosthesis Composite. PMID- 26855635 TI - Episode of Care Payments in Total Joint Arthroplasty and Cost Minimization Strategies. AB - Total joint arthroplasty (TJA) is receiving significant attention in the US health care system for cost containment strategies. Specifically, payer organizations have embraced and are implementing bundled payment schemes in TJA. Consequently, hospitals and providers involved in the TJA care cycle have sought to adapt to the new financial pressures imposed by episode of care payment models by analyzing what components of the total "event" of a TJA are most essential to achieve a good outcome after TJA. As part of this review, we analyze and discuss a health economic study by Snow et al. As part of their study, the authors aimed to understand the association between preoperative physical therapy (PT) and post acute care resource utilization, and its effect on the total cost of care during total joint arthroplasty. The purpose of this current review therefore is to (1) describe and analyze the findings presented by Snow et al. and (2) provide a framework for analyzing and critiquing economic analyses in orthopedic surgery. The study under review, while having important strengths, has several notable limitations that are important to keep in mind when making policy and coverage decisions. We support cautious interpretation and application of study results, and we encourage maintained attention to economic analysis in orthopedics as well as continued care path redesign to maximize value for patients and health care providers. PMID- 26855636 TI - Quality of Life Following ACL Reconstruction: Baseline Predictors of Patient Reported Outcomes. AB - The study by Dunn et al., "Baseline Predictors of Health-Related Quality of Life after Anterior Cruciate Ligament Reconstruction: A longitudinal analysis of a multicenter cohort at two and six years," evaluates patient factors that are predictive of outcomes following anterior cruciate ligament reconstruction. The current review critically analyzes the findings of this study in light of the current body of literature on the subject and assesses its contribution to the development of evidence-based guidelines. The authors' primary endpoint, the Short Form-36 (SF-36), is used ubiquitously in health care research and allows their results to be compared across different disease states and studies. Despite its widespread use, the SF-36 has been shown to be sensitive to outcomes following anterior cruciate ligament reconstruction. The authors' use of generic health-related quality of life outcome as a primary endpoint represents an important contribution to the field, and their findings allow for improved preoperative counseling by identifying baseline patient factors that predict outcomes following anterior cruciate ligament reconstruction. Furthermore, by deriving utilities from SF-36 scores, the authors are able to assess the value of anterior cruciate ligament reconstruction as compared to other medical and surgical procedures. PMID- 26855637 TI - CANCER MUCOSA ANTIGENS A NOVEL PARADIGM IN CANCER IMMUNOTHERAPEUTICS. AB - Employing antigens with expression restricted to normal intestinal mucosa and derivative colorectal tumors - cancer mucosa antigens (CMAs) - represents a novel paradigm in anti-tumor immunotherapy. Immune compartmentalization limits tolerance to CMAs and restricts mucosa-targeted autoimmunity, allowing safe and effective immunotherapy for metastatic colorectal cancer. Guanylyl cyclase C (GCC), an intestine/colorectal cancer-restricted protein, is poised for clinical evaluation as the index CMA. PMID- 26855638 TI - Aggression and Violence in Sport: Moving Beyond the Debate. AB - This paper is the latest in a series of articles published in The Sport Psychologist in recent years on aggression and violence in sport (Kerr, 1999, 2002; Tenenbaum, Sacks, Miller, Golden, & Doolin, 2000; Tenenbaum, Stewart, Singer, & Duda, 1997). While these respective articles have presented dissenting views on the nature and prevention of aggression and violence in sport, the present paper proposes that much of the apparent disagreement is semantic in nature. Thus, this paper begins by clarifying some definitional issues before specifying both areas of agreement and continued dissention among recent authors. Major emphases in this paper include the importance of adopting preventative rather than reactive measures to reduce the dangers associated with aggression and violence in sport, as well as the manner in which adult sport norms affect youth sport environments. In addition, several broader issues, which have emerged from these recent published debates, are presented for future consideration. PMID- 26855639 TI - Design Principles for Metal Oxide Redox Materials for Solar-Driven Isothermal Fuel Production. AB - The performance of metal oxides as redox materials is limited by their oxygen conductivity and thermochemical stability. Predicting these properties from the electronic structure can support the screening of advanced metal oxides and accelerate their development for clean energy applications. Specifically, reducible metal oxide catalysts and potential redox materials for the solar thermochemical splitting of CO2 and H2O via an isothermal redox cycle are examined. A volcano-type correlation is developed from available experimental data and density functional theory. It is found that the energy of the oxygen vacancy formation at the most stable surfaces of TiO2, Ti2O3, Cu2O, ZnO, ZrO2, MoO3, Ag2O, CeO2, yttria-stabilized zirconia, and three perovskites scales with the Gibbs free energy of formation of the bulk oxides. Analogously, the experimental oxygen self-diffusion constants correlate with the transition-state energy of oxygen conduction. A simple descriptor is derived for rapid screening of oxygen-diffusion trends across a large set of metal oxide compositions. These general trends are rationalized with the electronic charge localized at the lattice oxygen and can be utilized to predict the surface activity, the free energy of complex bulk metal oxides, and their oxygen conductivity. PMID- 26855640 TI - Empirical measurement of illicit tobacco trade in the Philippines. AB - Cigarette smuggling reduces the price of cigarettes, thwarts youth access restrictions, reduces government revenue, and undercuts the ability of taxes to reduce consumption. The tobacco industry often opposes increases to tobacco taxes on the claim that greater taxes induce more smuggling. To date, little is known about the magnitude of smuggling in the Philippines. his information is necessary to effectively address illicit trade and to measure the impacts of tax changes and the introduction of secure tax markings on illicit trade. This study employs two gap discrepancy methods to estimate the magnitude of illicit trade in cigarettes for the Philippines between 1994 and 2009. First, domestic consumption is compared with tax-paid sales to measure the consumption of illicit cigarettes. Second, imports recorded by the Philippines are compared with exports to the Philippines by trade partners to measure smuggling. Domestic consumption fell short of tax-paid sales for all survey years. The magnitude of these differences and a comparison with a prevalence survey for 2009 suggest a high level of survey under-reporting of smoking. In the late 1990s and the mid 2000s, the Philippines experienced two sharp declines in trade discrepancies, from a high of $750 million in 1995 to a low of $133.7 million in 2008. Discrepancies composed more than one-third of the domestic market in 1995, but only 10 percent in 2009. Hong Kong, Singapore, and China together account for more than 80 percent of the cumulative discrepancies over the period and 74 percent of the discrepancy in 2009. The presence of large discrepancies supports the need to implement an effective tax marking and tobacco track and trace system to reduce illicit trade and support tax collection. The absence of a relation between tax changes and smuggling suggests that potential increases in the excise tax should not be discouraged by illicit trade. Finally, the identification of specific trade partners as primary sources for illicit trade may facilitate targeted efforts in cooperation with these governments to reduce illicit trade. PMID- 26855642 TI - Simultaneous transfemoral transcatheter mitral and tricuspid valve edge-to-edge repair (using MitraClip system) completed by atrial septal defect occlusion in a surgically inoperable patient. First-in-human report. AB - Transcatheter transfemoral mitral valve repair using the MitraClip system (Abbott Vascular, USA) is used in high-risk or inoperable patients with severe mitral regurgitation. We report the first-in-human simultaneous transfemoral clipping of the mitral and tricuspid valve completed by occlusion of an atrial septal defect (ASD). The procedure was performed in an 84-year-old patient in October 2015. After effective reduction of mitral and tricuspid regurgitations using the MitraClip system a PFO Occluder (St. Jude Medical, USA) was implanted. Transfemoral simultaneous mitral and tricuspid valve repair using the MitraClip system with ASD occlusion seems to be an effective therapy for high-risk or inoperable patients. PMID- 26855643 TI - Stand-alone totally thoracoscopic left atrial appendage exclusion using a novel clipping system in patients with high risk of stroke - initial experience and literature review. AB - INTRODUCTION: Atrial fibrillation (AF) is the most common clinically relevant arrhythmia and it is strongly associated with stroke. Left atrial appendage (LAA) is considered to be the most often source of thrombotic material. In recent decades a number surgical, percutaneous and hybrid approaches for LAA occlusion have been described revealing very different level of success and showing a variety of challenges associated with this matter. We present the first Polish experience with the stand-alone totally thoracoscopic LAA exclusion using novel clipping system. MATERIAL AND METHODS: Four patients (one male) in mean age of 74 (+/- 13) years with long-standing persistent and chronic AF were admitted for totally thoracoscopic LAA exclusion. All patients had significant comorbidities and the history of the oral anticoagulation intolerance or suboptimal/unstable level (CHA2DS2-VASC > 5, HAS_BLED > 3). Three procedures were performed through totally thoracoscopic access. In one patient due to massive adhesions in the left pleura we performed minithoracotomy in fourth left intercostal space. In two months follow-up we observed no mortality, no strokes and no bleedings. RESULTS: In all patient total exclusion of LAA with no residual remnant was confirmed. The "skin-to-skin" procedural time took on average 40, minimum 20 minutes. Patients were extubated directly or within two hours after procedure. All patients were discharged early in a good condition. CONCLUSIONS: Our initial first experience with the novel totally thoracoscopic clipping system for stand-alone LAA exclusion is very promising showing very high efficacy and good safety profile. PMID- 26855644 TI - Coronary endarterectomy in left anterior descending artery combined with coronary artery bypass grafting - midterm mortality and morbidity. AB - INTRODUCTION: Completeness of myocardial revascularization is essential in surgical treatment of coronary artery disease. The aim of this study is to determine the effectiveness of coronary endarterectomy as an adjunct to coronary artery bypass grafting (CABG) in the most difficult cases. MATERIAL AND METHODS: Among 1559 patients who had CABG in our department, the cases of 17 who underwent an adjunct left anterior descending endarterectomy were analyzed. All procedures were performed with median sternotomy, extracorporeal circulation and in mild hypothermia (34 degrees C), by the same surgeon. No coronary artery endarterectomy was planned before surgery. RESULTS: There was no infarction or cardiac arrest during hospitalization. Only one patient required mechanical circulatory support (intra-aortic balloon counterpulsation). Each patient was contacted and investigation for major adverse cardiac and cerebrovascular events (MACCE) was performed. Eleven patients (65%) already underwent midterm clinical evaluation. There was no death, myocardial infarction or cerebrovascular incident during the entire period (mean follow-up at 15.3 months). One patient required urgent coronarography due to chest pain. No other patient had chest pain or significant deterioration of ventricular function in echocardiography. CONCLUSIONS: Outcomes and potential indications for performing left anterior descending coronary endarterectomy as an adjunct to CABG are discussed. PMID- 26855645 TI - Long-term efficacy of surgical ablation of atrial fibrillation in a low-volume centre. AB - Surgical ablation is a recommended procedure for patients with atrial fibrillation (AF) undergoing a cardiac surgery operation. However, the procedure is associated with significant risk of late recurrence of AF. The aim of the study was to assess the long-term efficacy of the procedure with respect to the comorbidities. The study group consisted of 22 patients: 9 women and 13 men, who underwent surgical AF ablation in the 2008-2013 period. The patients were interviewed by telephone and were asked to send their recently performed 12-lead electrocardiography (ECG). The semi-structured interview consisted of 25 items regarding the history of AF, concomitant comorbidities, lifelong syncopal history, smoking, family history of premature cardiovascular diseases, and current medical treatment. Furthermore, the Epworth test was performed to measure the daytime sleepiness, which in turn is related to the presence of obstructive sleep apnoea. On the basis of the obtained data, the CHADS2, and Epworth scale scores were calculated for each patient. As a result of the study six patients (27%) had sinus rhythm or paced dual chamber rhythm, and 16 patients had atrial fibrillation. The multivariate analysis revealed that Epworth scale scoring > 9, CHADS2 score > 0, and persistent type of AF were related to poor outcome of surgical ablation procedure. In conclusion, patients with AF treated with surgical ablation have similar prognosis of sinus rhythm maintenance to those treated with radiofrequency ablation. Moreover, the same predisposing factors play a significant role in AF recurrence both in surgical patients and in patients treated with radiofrequency ablation. PMID- 26855646 TI - Aortic cusp extension valvuloplasty: repair with an extracellular patch. AB - INTRODUCTION: The proportion of valve repair procedures is increasing in experienced centers. The aim of the study was to assess the clinical and echocardiographic outcomes after aortic valve reconstruction with a novel surgical technique. MATERIAL AND METHODS: The study group consisted of 30 patients (23 male and 7 female) at a mean age of 35 +/- 14 years. In patients with aortic root aneurysm the reimplantation or Florida sleeve technique was used. A sub-commissural annuloplasty, plication of the free edge of the cusp, shaving, and commissurotomy were performed. At this stage of surgery aortic repair was then attempted by cusp extension. Since 2013 the strips have been tailored from extracellular matrix. RESULTS: The mean aortic cross-clamp time was 90 +/- 32 min. The mean cardiopulmonary bypass time was 126 +/- 38 min. There was no in-hospital death. Re-exploration for bleeding was required in 1 patient. During follow-up, 1 patient needed reoperation at 1 year due to endocarditis. All patients remained alive in New York Heart Association (NYHA) functional class I. The echocardiographic findings remained unchanged in all cases during follow-up. CONCLUSIONS: Our modification of aortic valve repair results in a good outcome. PMID- 26855647 TI - Total mechanical stapled oesophagogastric anastomosis on the neck in oesophageal cancer - prevention of postoperative mediastinal complications. AB - Oesophagogastric anastomosis after oesophagus resection is commonly performed on the neck. Even though a few different techniques of oesophagogastric anastomosis have been previously detailed, both manual and mechanical procedures have been burdened with leakages and strictures. Our simple technique of oesophagogastric anastomosis is a modification of mechanical anastomosis with the use of a circular stapler in order to prevent postoperative leak and concomitant mediastinal complications. Since 2008, we have performed nine oesophagogastric anastomoses following oesophagus resection. The mean age of the operated patients was 54 years. There was no mortality among the operated patients in the early post-operative period. The mean follow-up period for the patients operated on in our department was 17 months until the time of the analysis. None of the patients showed any leakage or stricture, and no mediastinal complications were reported in the group. Following our own experience, mechanical anastomosis with the use of a circular stapler seems to decrease the time of the operation as well as significantly reducing the incidence of leakages from the anastomosis. This type of anastomosis may decrease the number of postoperative strictures and the most dangerous mediastinal infections. PMID- 26855648 TI - Spontaneous pneumothorax in children - management, results, and review of the literature. AB - INTRODUCTION: Primary spontaneous pneumothorax (PSP) occurs at a frequency of 7.4 18 cases per 100 000 population per year. The PSP typically occurs in young adults and is uncommon in children. The aim of this study was to review our institutional experience with PSP in children. MATERIAL AND METHODS: Twenty-two paediatric patients with confirmed PSP, treated from 2004 to 2014 at the Paediatric Surgery Clinic. There were 18 boys and 4 girls. The mean age was 16 years, 6 months +/- 1 month (range 14-17). The mean body mass index (BMI) was 20.1 (ranging from 17 to 24). RESULTS: The recurrence rate of PSP was 48%. The mean interval of the recurrence was 5 months +/- 1 month (range from 3 weeks to 2 years). Recurrent pneumothorax was evacuated by thoracostomy with success in four patients. The first video-assisted thoracoscopic surgery (VATS) procedure had a failure rate of 50%. After second VATS procedure, we did not observe recurrent PSP in two patients. One patient with recurrent PSP, after two VATS procedures, was treated with success, with an open mini axillary thoracotomy. The mean follow up period was 4 years 3 months +/- 1 month (range 6 months - 10 years). We have not noted any intraoperative complications. CONCLUSIONS: Although our study is limited by the small number of patients, we conclude that most patients resolve their spontaneous pneumothorax and air leak with tube thoracostomy alone. For those patients in whom chest tube drainage is not effective, and for those with recurrent PSP, early VATS and bullectomy combined with pleural abrasion is the most efficient intervention. PMID- 26855649 TI - Risk factors of cardiac allograft vasculopathy. AB - Despite advances in prevention and treatment of heart transplant rejection, development of cardiac allograft vasculopathy (CAV) remains the leading factor limiting long-term survival of the graft. Cardiac allograft vasculopathy etiopathogenesis is not fully understood, but a significant role is attributed to endothelial cell damage, caused by immunological and non-immunological mechanisms. Immunological factors include the differences between the recipient's and the donor's HLA systems, the presence of alloreactive antibodies and episodes of acute rejection. Among the non-immunological factors the most important are the age of the donor, ischemia-reperfusion injury and cytomegalovirus infection. The classical cardiovascular risk factors (diabetes, hypertension, obesity and hyperlipidemia) are also important. This study presents an up-to-date overview of current knowledge on the vasculopathy etiopathogenesis and the role played by endothelium and inflammatory processes in CAV, and it also investigates the factors which may serve as risk markers of cardiac allograft vasculopathy. PMID- 26855650 TI - Factors affecting the quality of anticoagulation with warfarin: experience of one cardiac centre. AB - INTRODUCTION: The risk of complications in anticoagulation therapy can be reduced by maximising the percentage of time spent by the patient in the optimal therapeutic range (TTR). However, little is known about the predictors of anticoagulation control. The aim of this paper was to assess the quality of anticoagulant therapy in patients on warfarin and to identify the factors affecting its deterioration. MATERIAL AND METHODS: We studied 149 patients who required anticoagulant therapy with warfarin due to non-valvular atrial fibrillation and/or venous thromboembolism. Each patient underwent proper training regarding the implemented treatment and remained under constant medical care. RESULTS: The mean age of the patients was 68.8 +/- 12.6 years, and 59% were male. A total of 2460 international normalised ratio (INR) measurements were collected during the 18-month period. The mean TTR in the studied cohort was 76 +/- 21%, and the median was 80%. The level at which high-quality anticoagulation was recorded for this study was based on TTR values above 80%. Seventy-five patients with TTR >= 80% were included in the stable anticoagulation group (TTR >= 80%); the remaining 74 patients constituted the unstable anticoagulation group (TTR < 80%). According to multivariate stepwise regression analysis, the independent variables increasing the risk of deterioration of anticoagulation quality were: arterial hypertension (OR 2.74 [CI 95%: 1.06-7.10]; p = 0.038), amiodarone therapy (OR 4.22 [CI 95%: 1.30-13.70]; p = 0.017), and obesity (OR 1.11 [CI 95%: 1.02-1.21]; p = 0.013). CONCLUSIONS: The presence of obesity, hypertension, or amiodarone therapy decreases the quality of anticoagulation with warfarin. High quality of anticoagulation can be achieved through proper monitoring and education of patients. PMID- 26855651 TI - Pulmonary artery aneurysm in an adult patient with idiopathic dilatation of the pulmonary artery. AB - Idiopathic dilatation of the pulmonary artery (IDPA) is a rare congenital heart disease. It has been described for almost one hundred years, and numerous definitions have been proposed. The IDPA diagnostic criteria have not been updated for years. Secondary to primary disease, pulmonary artery aneurism was recognised as a lethal defect; however, long-term follow-up of patients with IDPA has not been well researched. Thus, indications to medical or surgical treatment are not evidence based. Here, we present a rare case of a 54-year-old patient with IDPA, who remained under observation for 36 years without surgical intervention. PMID- 26855652 TI - Conservative approach to mitral valve replacement in hypertrophic cardiomyopathy with systolic anterior motion - a case report. AB - The authors report the case of a 60-year-old patient with hypertrophic cardiomyopathy (HCM), systolic anterior motion (SAM), and high gradient in the left ventricular outflow tract (LVOT) who underwent surgical treatment. During the surgery, myomectomy of the septum was performed using the Morrow method: despite the persisting SAM and increased LVOT gradients, the mitral valve was not replaced. The case study presents a conservative approach to mitral valve replacement during HCM surgery. PMID- 26855653 TI - Simultaneous removal of a tumour of the right atrium and inferior vena cava and coronary bypass-grafting in a patient with recurrent clear renal cell carcinoma. AB - Metastatic cardiac tumours are the most common malignant cardiac tumours. In the early stages they are usually asymptomatic, but their consequences can be very serious, and the prognosis is poor. We present a patient with recurrent renal cell carcinoma as a tumour of the right atrium and the vena cava inferior in whom cancerous masses were removed with simultaneously coronary artery bypass grafting. PMID- 26855654 TI - Single lung transplantation in a patient with retrospective positive cross-match. AB - Lung transplantation is a method useful in such non-malignant end-stage parenchymal and vascular diseases as: chronic obstructive pulmonary disease (COPD), idiopathic interstitial pulmonary fibrosis, cystic fibrosis, or primary pulmonary hypertension. The main aim of this procedure is to extend the patient's lifespan and quality of life. However, the availability of the operation is limited by organ access. In this paper we present the case of a 58-year-old female in the fourth stage of COPD, who was classified to have a single lung transplantation. Because of some technical problems it was decided to transplant a left donor lung in the right recipient lung locus. Positive cross match was demonstrated retrospectively, and we applied five courses of plasmapheresis. Human immunoglobulin and rituximab treatment were performed to decrease the impact of lymphocytotoxic antibodies. The patient survived 498 days after transplantation, 271 in the hospital. PMID- 26855655 TI - Bilateral elastofibroma dorsi: a case report of an uncommon and under-diagnosed tumor. AB - Elastofibroma dorsi is a rare benign tumor of the back, located between the latissimus dorsi and the rhomboid muscle. In most cases it is unilateral, but in up to 10% it occurs on both sides. The etiology is still in discussion. Here we report a case of a 51-year-old man with bilateral elastofibroma dorsi. The therapy of choice was surgical resection. No long-term complications were reported in a 6-month follow-up. PMID- 26855656 TI - Tension pneumothorax as a severe complication of endobronchial ultrasound-guided transbronchial fine needle aspiration of mediastinal lymph nodes. AB - This article presents a case report of a patient suffering from bullous emphysema and chronic obstructive pulmonary disease, who was diagnosed with tension pneumothorax after undergoing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Tension pneumothorax is a severe but rare complication of EBUS-TBNA. It can result from lung injury caused by the biopsy needle or, in patients suffering from bullous emphysema, from spontaneous rupture of an emphysematous bulla resulting from increased pressure in the chest cavity during cough caused by bronchofiberoscope insertion. The authors emphasize that patients should be carefully monitored after the biopsy, and, in the case of complications, provided with treatment immediately in proper hospital conditions. Patients burdened with a high risk of complications should be identified before the procedure and monitored with extreme care after its completion. PMID- 26855657 TI - Stage IIIa cancer of the right lung ingrowing via right lower pulmonary vein to the left heart atrium. AB - Computed tomography is performed in every patient before lung tumour resection. The presented case realises how important it is to perform this study with contrast. In a 75-year-old male we detected a tumour ingrowing from the right lung through the right lower pulmonary vein into the left atrium of the heart. The patient was qualified for primary sternotomy with extracorporeal circulation and resection of the intracardiac part of the tumour. In the second stage, right sided thoracotomy was performed, and right lower lung lobectomy was done. Mixed heterogeneous lung cancer was diagnosed (squamous cell and non-small cell endocrine) in stage IIIa. The perioperative period was uncomplicated. The patient, due to renal failure, was not eligible for adjuvant chemotherapy. If the patient were qualified for lobectomy based directly on computed tomography without contrast, there would have been a high risk of perioperative death due to embolic incidents and heart failure. Effective multidisciplinary collaboration allowed us to avoid this sort of complication. PMID- 26855658 TI - Diffuse pulmonary haemorrhage accompanied by haemothorax as a rare presentation of primary lung angiosarcoma. AB - Primary pulmonary angiosarcoma is an extremely rare disease. Chest computed tomography demonstrates solitary or multifocal lesions, sometimes associated with ground-glass opacities or pleural effusion. Diagnosis is based on histological examination that reveals spindle-shaped epithelioid cells with positive staining for endothelial markers (factor VIII, CD 31, CD34, Fli-1, Ulex europaeus agglutinin 1, vimentin). The prognosis is poor and effective treatment is still being researched. This is a report of a 65-year-old patient with a four-month history of haemoptysis, cough, and dyspnoea. The primary radiological findings suggested interstitial lung disease. After one month the clinical presentation evolved into diffuse pulmonary haemorrhage with concomitant haemothorax. The diagnosis of primary lung angiosarcoma was based on histological and immunohistochemical examination of the lung and pleural biopsy obtained by videothoracoscopy. PMID- 26855659 TI - The usefulness of ultrasound in the diagnosis of patients after chest trauma - two case reports. AB - The effectiveness of ultrasound in diagnosing fractures of the ribs and sternum has been confirmed in the literature. The aim of our study was to present two case reports of patients with chest trauma history in whom ultrasound examination proved useful in the diagnostic process. The role of thoracic ultrasound in the diagnosis of ribs and sternal fractures is discussed as well. The authors conclude the following: 1) the examination was easy to perform and assess, and provided clinically useful conclusions; 2) due to the mobility of the ultrasound machine, the examination may be carried out outside of radiology departments, e.g. by the patient's bedside - in departments of surgery; 3) ultrasound should be the examination of choice after chest trauma and can be performed successfully by non-radiologist physicians. PMID- 26855660 TI - Hypothyroidism complicates bradyarrhythmic episodes in a heart-transplanted patient: Can it be treated with low-dose dopamine? AB - Extracorporeal circulation decreases thyroid hormone levels in peripheral blood. This clinical entity may complicate the postoperative period after heart transplantation if the recipient has taken thyroid hormone replacement therapy. Cardiac transplantation was performed on a patient in whom thyroid hormone levels decreased after surgery. Sinus bradycardia was seen after surgery (30-40 bpm). Thyroid hormones were replaced in the patient. Due to the fact that temporary pacing decreased blood pressure, dopamine was safely given in very low doses. This case was discussed under the literature knowledge. PMID- 26855662 TI - The impact of resistance respiratory muscle training with a SpiroTiger((r)) device on lung function, exercise performance, and health-related quality of life in respiratory diseases. AB - INTRODUCTION: There are studies demonstrating that respiratory muscles can be trained using proper stimulation. Positive effects have been achieved in patients with pulmonary diseases and in patients after thoracic surgery procedures using isocapnic hyperpnoea training with a SpiroTiger((r)) device. The aim of this study was to investigate whether SpiroTiger((r)) training has an impact on forced expiratory volume in one second (FEV1), exercise performance, respiratory muscle fitness, and health-related quality of life. MATERIAL AND METHODS: Search phrases "spirotiger" and "spiro tiger" were entered into the search engines of the following databases: Academic Search Complete, Medline, Ebscohost, and PubMed. RESULTS: One article about chronic obstructive pulmonary disease (COPD) and 4 articles about cystic fibrosis were found. CONCLUSIONS: The positive effect of SpiroTiger((r)) training on FEV1 cannot be unequivocally confirmed as it was found only in two of the five analysed studies. SpiroTiger((r)) training has a positive impact on exercise performance measured with the six-minute walk test; it increases breathing muscle fitness in patients with COPD and in patients after thoracic surgery procedures, and it improves health-related quality of life. PMID- 26855661 TI - Predominant location of coronary artery atherosclerosis in the left anterior descending artery. The impact of septal perforators and the myocardial bridging effect. AB - INTRODUCTION: Coronary artery atherosclerosis presents characteristic patterns of plaque distribution despite systemic exposure to risk factors. We hypothesized that local hemodynamic forces induced by the systolic compression of intramuscular septal perforators could be involved in atherosclerotic processes in the left anterior descending artery (LAD) adjacent to the septal perforators' origin. Therefore we studied the spatial distribution of atherosclerosis in coronary arteries, especially in relation to the septal perforators' origin. MATERIAL AND METHODS: 64-slice computed tomography angiography was performed in 309 consecutive patients (92 male and 217 female) with a mean age of 59.9 years. Spatial plaque distribution in the LAD was analyzed in relation to the septal perforators' origin. Additionally, plaque distribution throughout the coronary artery tree is discussed. RESULTS: The coronary calcium score (CCS) was positive in 164 patients (53.1%). In subjects with a CCS > 0, calcifications were more frequent in the LAD (n = 150, 91.5%) compared with the right coronary artery (RCA) (n = 94, 57.3%), circumflex branch (CX) (n = 76, 46.3%) or the left main stem (n = 42, 25.6%) (p < 0.001). Total CCS was higher in the LAD at 46.1 (IQR: 104.2) and RCA at 34.1 (IQR: 90.7) than in the CX at 16.8 (IQR: 61.3) (p = 0.007). In patients with calcifications restricted to a single vessel (n = 54), the most frequently affected artery was the LAD (n = 42, 77.8%). In patients with lesions limited to the LAD, the plaque was located mostly (n = 37, 88.1%) adjacent to the septal perforators' origin. CONCLUSIONS: We demonstrated that coronary calcifications are most frequently located in the LAD in proximity to the septal branch origin. A possible explanation for this phenomenon could be the dynamic compression of the tunneled septal branches, which may result in disturbed blood flow in the adjacent LAD segment (milking effect). PMID- 26855663 TI - Sero-prevalence of HBV and associated risk factors among HIV positive individuals attending ART clinic at Mekelle hospital, Tigray, Northern Ethiopia. AB - BACKGROUND: Because of the shared mean of transmission, hepatitis B virus (HBV) is one of an important cause of co-morbidity and mortality in peoples living with HIV/AIDS. Hence, the aim of this study was to determine the sero-prevalence of HBV infection and associated risk factors in HIV/AIDS positive individuals attending ART clinic at Mekelle hospital, Mekelle, Northern Ethiopia. METHODS: A cross sectional study was conducted from August to October 2014 in HIV/AIDS positive adult individuals. Socio-demographic data and other explanatory variables were collected from 508 study participants using pre-tested and structured questionnaire-based interviews. Serum hepatitis B surface antigen (HBsAg) was detected using commercially available rapid test and third generation enzyme-linked immunosorbent assay (ELISA). Bivariate and multivariate analysis, using SPSS V.20.0, were performed to assess the variables associated with HBV infection and P value less than 0.05 was considered as statistically significant. RESULTS: A total of 508 study participants, 305 females and 203 males were included in this study with the mean (+SD) age of 37.8 + 9.6. The sero-prevalence of HBsAg was 5.9 %. Male gender (AOR = 2.6, 95 % CI 1.2-5.7), multiple sexual partners (AOR = 4.2, 95 % CI 1.3-13.1) and CD4 count <200 cells/MUl (AOR = 3.5, 95 % CI 1.1-11.2) were significantly associated with HBsAg positivity. CONCLUSION: The prevalence of HBsAg was similar to the general population. However, HIV/AIDS positive individuals with reduced CD4 count, <200 cells/MUl, showed a significant association with HBsAg seropositivity. Therefore, we recommended, all HIV/AIDS positive individuals should be screened for HBsAg during their follow for better treatment outcome and minimize risks of HBV transmission. PMID- 26855664 TI - Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. AB - BACKGROUND: Nutritional ketosis induced by the ketogenic diet (KD) has therapeutic applications for many disease states. We hypothesized that oral administration of exogenous ketone supplements could produce sustained nutritional ketosis (>0.5 mM) without carbohydrate restriction. METHODS: We tested the effects of 28-day administration of five ketone supplements on blood glucose, ketones, and lipids in male Sprague-Dawley rats. The supplements included: 1,3-butanediol (BD), a sodium/potassium beta-hydroxybutyrate (betaHB) mineral salt (BMS), medium chain triglyceride oil (MCT), BMS + MCT 1:1 mixture, and 1,3 butanediol acetoacetate diester (KE). Rats received a daily 5-10 g/kg dose of their respective ketone supplement via intragastric gavage during treatment. Weekly whole blood samples were taken for analysis of glucose and betaHB at baseline and, 0.5, 1, 4, 8, and 12 h post-gavage, or until betaHB returned to baseline. At 28 days, triglycerides, total cholesterol and high density lipoprotein (HDL) were measured. RESULTS: Exogenous ketone supplementation caused a rapid and sustained elevation of betaHB, reduction of glucose, and little change to lipid biomarkers compared to control animals. CONCLUSIONS: This study demonstrates the efficacy and tolerability of oral exogenous ketone supplementation in inducing nutritional ketosis independent of dietary restriction. PMID- 26855666 TI - Early intranasal insulin therapy halts progression of neurodegeneration: progress in Alzheimer's disease therapeutics. AB - Evaluation of Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal Insulin Therapy for Alzheimer Disease and Amnestic Mild Cognitive Impairment: A Pilot Clinical Trial. Arch Neurol. 2011 Sep 12. Alzheimer's disease is associated with brain insulin deficiency and insulin resistance, similar to the problems in diabetes. If insulin could be supplied to the brain in the early stages of Alzheimer's, subsequent neurodegeneration might be prevented. Administering systemic insulin to elderly non-diabetics poses unacceptable risks of inadvertant hypoglycemia. However, intranasal delivery directs the insulin into the brain, avoiding systemic side-effects. This pilot study demonstrates both efficacy and safety of using intranasal insulin to treat early Alzheimer's and mild cognitive impairment, i.e. the precursor to Alzheimer's. Significant improvements in learning, memory, and cognition occured within a few months, but without intranasal insulin, brain function continued to deteriorate in measurable degrees. Intranasal insulin therapy holds promise for halting progression of Alzheimer's disease. PMID- 26855667 TI - Erratum to: Impact of human papillomavirus on head and neck squamous cell cancers in Gabon. AB - [This corrects the article DOI: 10.1186/s13027-015-0036-7.]. PMID- 26855665 TI - Randomized clinical study: Partially hydrolyzed guar gum (PHGG) versus placebo in the treatment of patients with irritable bowel syndrome. AB - BACKGROUND: The treatment of Irritable bowel syndrome (IBS) is still challenging. Partially hydrolyzed guar gum (PHGG) is a known prebiotic fiber. To assess the effects of PHGG on clinical symptoms of IBS patients in a prospective randomized double blind placebo-controlled study. METHODS: Suitable IBS patients were recruited into an 18-week-long study (2 weeks of run-in, 12 weeks of treatment and 4 weeks of follow-up). They were blindly randomized to receive 6 gr of PHGG or placebo. Treatment efficacy was evaluated by the Francis Severity IBS score, the IBS quality-of-life scores and scored parameters of weekly journal of symptoms. Deltas of changes between the final and baseline scores were compared between two groups. RESULTS: Of 121 patients who underwent randomization, 108 patients (49 in the PHGG group and 59 in the placebo group) had all the data needed for intention-to-treat analysis. A 12-week administration of PHGG led to a significant improvement of journal bloating score in the PHGG group versus placebo (-4.1+/-13.4 versus -1.2+/-11.9, P=0.03), as well as in bloating+gasses score (-4.3+/-10.4 versus -1.12+/-10.5, P = 0.035). The effect lasted for at least 4 weeks after the last PHGG administration. PHGG had no effect on other journal reported IBS symptoms or on Severity and Quality of life scores. There were no significant side effects associated with PHGG ingestion. The rate of dropouts was significantly higher among patients in the placebo group compared with the PHGG group (49.15% versus 22.45%, respectively, P = 0.01). CONCLUSIONS: The results of this study support the administration of 6 g/day PHGG for IBS patients with bloating. TRIAL REGISTRATION: NCT01779765. PMID- 26855669 TI - Consumers and Carer perspectives on poor practice and the use of seclusion and restraint in mental health settings: results from Australian focus groups. AB - BACKGROUND: Seclusion and restraint are interventions currently permitted for use in mental health services to control or manage a person's behaviour. In Australia, serious concerns about the use of such seclusion and restraint have been raised at least since 1993. Consumers and their supporters have also expressed strong views about the harm of these practices. This paper presents the results of ten focus group discussions with people with lived experience of mental health issues and also carers, family members and support persons in relation to the use of seclusion and restraint. METHODS: The 30 consumers and 36 supporters participating in the focus groups convened in four Australian cities and one regional centre discussed their understandings of the use of seclusion and restraint and its impact on the people involved. Participants also presented their observations about poor practice and what contributes to it as well as providing ideas and recommendations regarding strategies to reduce or eliminate seclusion and restraint. Focus group discussions were recorded and transcribed, then analysed using the NVivo 10 qualitative data analysis software with a general inductive approach used to analyse data. This analysis enabled consideration of the responses to key questions in the focus groups as well as the identification of emerging themes. RESULTS: Six themes emerged from the analysis, these being: human rights, trauma, control, isolation, dehumanisation and 'othering', and anti-recovery. Examples of poor practice identified by focus groups included the use of excessive force, lack of empathy/paternalistic attitudes, lack of communication and interaction and a lack of alternative strategies to the use of seclusion and restraint. There was a confluence of factors identified by participants as contributing to poor practice, with the main factors being organisational culture, the physical environment, under resourced mental health services and fear and stigma. CONCLUSIONS: Focus group participants in the main viewed seclusion and restraint practices in mental health settings as unnecessarily overused, exacerbating problems for individuals, carers, staff and the broader system of care. This study highlights that lived experience of both consumers and their supporters can make an important contribution to mental health services and its ongoing reform. PMID- 26855668 TI - Synthesis and biological evaluation of new 1,3-thiazolidine-4-one derivatives of nitro-l-arginine methyl ester. AB - BACKGROUND: l-Arginine is a semi-essential aminoacid with important role in regulation of physiological processes in humans. It serves as precursor for the synthesis of proteins and is also substrate for different enzymes such as nitric oxide synthase. This amino-acid act as free radical scavenger, inhibits the activity of pro-oxidant enzymes and thus acts as an antioxidant and has also bactericidal effect against a broad spectrum of bacteria. RESULTS: New thiazolidine-4-one derivatives of nitro-l-arginine methyl ester (NO2-Arg-OMe) have been synthesized and biologically evaluated in terms of antioxidant and antibacterial/antifungal activity. The structures of the synthesized compounds were confirmed by (1)H, (13)C NMR, Mass and IR spectral data. The antioxidant potential was investigated using in vitro methods based on ferric/phosphomolybdenum reducing antioxidant power and DPPH/ABTS radical scavenging assay. The antibacterial effect was investigated against Gram positive (Staphylococcus aureus ATCC 25923, Sarcina lutea ATCC 9341) and Gram negative (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853) bacterial strains. The antifungal activity was also investigated against Candida spp. (Candida albicans ATCC 10231, Candida glabrata ATCC MYA 2950, Candida parapsilosis ATCC 22019). CONCLUSIONS: Synthesized compounds showed a good antioxidant activity in comparison with the NO2-Arg-OMe. The antimicrobial results support the selectivity of tested compounds especially on P. aeruginosa as bacterial strain and C. parapsilosis as fungal strain. The most proper compounds were 6g (R = 3-OCH3) and 6h (R = 2-OCH3) which showed a high free radical (DPPH, ABTS) scavenging ability and 6j (R = 2-NO2) that was the most active on both bacterial and fungal strains and also it showed the highest ABTS radical scavenging ability.Graphical abstract1: ethyl 3-aminopropionate hydrochloride, 2a-j: aromatic aldehydes, 3: thioglycolic acid, 4a-j: thiazolidine propionic acid derivatives , 5: Nomega-nitro-L-arginine methyl ester hydrochloride, 6a-j: thiazolidine-propionyl-nitro-L-arginine methyl ester derivatives. PMID- 26855670 TI - Consolidated bioprocessing of Populus using Clostridium (Ruminiclostridium) thermocellum: a case study on the impact of lignin composition and structure. AB - BACKGROUND: Higher ratios of syringyl-to-guaiacyl (S/G) lignin components of Populus were shown to improve sugar release by enzymatic hydrolysis using commercial blends. Cellulolytic microbes are often robust biomass hydrolyzers and may offer cost advantages; however, it is unknown whether their activity can also be significantly influenced by the ratio of different monolignol types in Populus biomass. Hydrolysis and fermentation of autoclaved, but otherwise not pretreated Populus trichocarpa by Clostridium thermocellum ATCC 27405 was compared using feedstocks that had similar carbohydrate and total lignin contents but differed in S/G ratios. RESULTS: Populus with an S/G ratio of 2.1 was converted more rapidly and to a greater extent compared to similar biomass that had a ratio of 1.2. For either microbes or commercial enzymes, an approximate 50 % relative difference in total solids solubilization was measured for both biomasses, which suggests that the differences and limitations in the microbial breakdown of lignocellulose may be largely from the enzymatic hydrolytic process. Surprisingly, the reduction in glucan content per gram solid in the residual microbially processed biomass was similar (17-18 %) irrespective of S/G ratio, pointing to a similar mechanism of solubilization that proceeded at different rates. Fermentation metabolome testing did not reveal the release of known biomass-derived alcohol and aldehyde inhibitors that could explain observed differences in microbial hydrolytic activity. Biomass-derived p-hydroxybenzoic acid was up to nine-fold higher in low S/G ratio biomass fermentations, but was not found to be inhibitory in subsequent test fermentations. Cellulose crystallinity and degree of polymerization did not vary between Populus lines and had minor changes after fermentation. However, lignin molecular weights and cellulose accessibility determined by Simons' staining were positively correlated to the S/G content. CONCLUSIONS: Higher S/G ratios in Populus biomass lead to longer and more linear lignin chains and greater access to surface cellulosic content by microbe-bound enzymatic complexes. Substrate access limitation is suggested as a primary bottleneck in solubilization of minimally processed Populus, which has important implications for microbial deconstruction of lignocellulose biomass. Our findings will allow others to examine different Populus lines and to test if similar observations are possible for other plant species. PMID- 26855671 TI - Consistent 1,3-propanediol production from glycerol in mixed culture fermentation over a wide range of pH. AB - BACKGROUND: Glycerol is currently an over-produced chemical that can be used as substrate for the production of high value products such as 1,3-propanediol (1,3 PDO) in fermentation processes. The aim of this study was to investigate the effect of initial pH on a batch mixed culture fermentation of glycerol, considering both the bacterial community composition and the fermentation patterns. RESULTS: For pH values between 5 and 9, 1,3-PDO production yields ranged from 0.52 +/- 0.01 to 0.64 +/- 0.00 [Formula: see text], with the highest values obtained at pH 7 and 8. An Enterobacteriaceae member closely related to Citrobacter freundii was strongly enriched at all pH values. Within the less dominant bacterial species, two different microbial community structures were found, one at acid pH values and another at neutral to basic pH values. CONCLUSIONS: 1,3-PDO production was improved at pH values over 7. It was anti correlated with lactate and ethanol production but positively correlated with acetate production. No direct correlation between 1,3-PDO production and a specific family of bacteria was found, suggesting functional redundancies in the microbial community. However, 1,3-PDO production yield remained high over the range of pH studied and was comparable to the best obtained in the same conditions in the literature. PMID- 26855672 TI - Assessing the quality of operation notes: a review of 1092 operation notes in 9 UK hospitals. AB - BACKGROUND: The General Medical Council states that effective note keeping is essential and records should be clear, accurate and legible. However previous studies of operation notes have shown they can be variable in quality and affect patient safety. This study compares the quality of operation notes against the National Standards set by the Royal College of Surgeons of England and the British Orthopaedic Association (BOA) for improving patient safety. METHODS: Information from Orthopaedic operation notes was collected prospectively over a 2 week period. All elective and trauma operations performed were included and trainees from the region coordinated data collection in 9 hospitals. RESULTS: Data from 1092 operation notes was reviewed. A number of important standards were nearly met including legibility (98.4 %), the name of the operating surgeon (99.3 %) and the operation title (99.1 %). However a number of standards were not met and those with potential patient safety implications include availability on the ward (88.8 %), documentation of type of anaesthetic used (78.6 %), diagnosis (73.4 %) and findings (80.1 %). In addition, the postoperative instructions recorded the need for and type of postoperative antibiotics or venous thromboembolism prophylaxis in only 49.7 % and 48.8 % of cases respectively. CONCLUSIONS: The quality and content of operation notes studied across the region in this period was variable. Use of software programmes in some hospitals for creating operation notes meant that some centres had better results for elements such as date, time and patient identification details. Following this study, greater awareness of the standards combined with additional local measures may improve the quality of operation notes. PMID- 26855673 TI - Proximal 21q deletion as a result of a de novo unbalanced t(12;21) translocation in a patient with dysmorphic features, hepatomegaly, thick myocardium and delayed psychomotor development. AB - BACKGROUND: IInterstitial 21q deletions can cause a wide spectrum of symptoms depending on the size and the location of the deletion. It has previously been suggested that the long arm of chromosome 21 can be divided into three regions based on the clinical severity of the patients and deletion of the region from 32.3 Mb to 37.1 Mb was more crucial than the deletion of other regions. CASE PRESENTATION: In this study we describe a female patient with dysmorphic features, hepatomegaly, thick myocardium and psychomotor delay. Conventional karyotyping was initially interpreted as full monosomy 21, but subsequent chromosome microarray analysis suggested an approximately 18 Mb partial monosomy. Re-evaluation of the karyotype and fluorescence in situ hybridization revealed deletion of the proximal 21q11.2-q22.11 segment and insertion of 21q22.11-qter to 12qter. The deletion of the present case overlaps with two of the proposed regions including part of the proposed crucial region. CONCLUSIONS: This report emphasizes the relevance of investigating suspected full monosomies with high resolution methods and FISH in order to investigate the extent of the deletion and the presence of more complex rearrangements. PMID- 26855674 TI - Selectivity profiling of BCRP versus P-gp inhibition: from automated collection of polypharmacology data to multi-label learning. AB - BACKGROUND: The human ATP binding cassette transporters Breast Cancer Resistance Protein (BCRP) and Multidrug Resistance Protein 1 (P-gp) are co-expressed in many tissues and barriers, especially at the blood-brain barrier and at the hepatocyte canalicular membrane. Understanding their interplay in affecting the pharmacokinetics of drugs is of prime interest. In silico tools to predict inhibition and substrate profiles towards BCRP and P-gp might serve as early filters in the drug discovery and development process. However, to build such models, pharmacological data must be collected for both targets, which is a tedious task, often involving manual and poorly reproducible steps. RESULTS: Compounds with inhibitory activity measured against BCRP and/or P-gp were retrieved by combining Open Data and manually curated data from literature using a KNIME workflow. After determination of compound overlap, machine learning approaches were used to establish multi-label classification models for BCRP/P gp. Different ways of addressing multi-label problems are explored and compared: label-powerset, binary relevance and classifiers chain. Label-powerset revealed important molecular features for selective or polyspecific inhibitory activity. In our dataset, only two descriptors (the numbers of hydrophobic and aromatic atoms) were sufficient to separate selective BCRP inhibitors from selective P-gp inhibitors. Also, dual inhibitors share properties with both groups of selective inhibitors. Binary relevance and classifiers chain allow improving the predictivity of the models. CONCLUSIONS: The KNIME workflow proved a useful tool to merge data from diverse sources. It could be used for building multi-label datasets of any set of pharmacological targets for which there is data available either in the open domain or in-house. By applying various multi-label learning algorithms, important molecular features driving transporter selectivity could be retrieved. Finally, using the dataset with missing annotations, predictive models can be derived in cases where no accurate dense dataset is available (not enough data overlap or no well balanced class distribution).Graphical abstract. PMID- 26855675 TI - Genome ARTIST: a robust, high-accuracy aligner tool for mapping transposon insertions and self-insertions. AB - BACKGROUND: A critical topic of insertional mutagenesis experiments performed on model organisms is mapping the hits of artificial transposons (ATs) at nucleotide level accuracy. Mapping errors may occur when sequencing artifacts or mutations as single nucleotide polymorphisms (SNPs) and small indels are present very close to the junction between a genomic sequence and a transposon inverted repeat (TIR). Another particular item of insertional mutagenesis is mapping of the transposon self-insertions and, to our best knowledge, there is no publicly available mapping tool designed to analyze such molecular events. RESULTS: We developed Genome ARTIST, a pairwise gapped aligner tool which works out both issues by means of an original, robust mapping strategy. Genome ARTIST is not designed to use next-generation sequencing (NGS) data but to analyze ATs insertions obtained in small to medium-scale mutagenesis experiments. Genome ARTIST employs a heuristic approach to find DNA sequence similarities and harnesses a multi-step implementation of a Smith-Waterman adapted algorithm to compute the mapping alignments. The experience is enhanced by easily customizable parameters and a user-friendly interface that describes the genomic landscape surrounding the insertion. Genome ARTIST is functional with many genomes of bacteria and eukaryotes available in Ensembl and GenBank repositories. Our tool specifically harnesses the sequence annotation data provided by FlyBase for Drosophila melanogaster (the fruit fly), which enables mapping of insertions relative to various genomic features such as natural transposons. Genome ARTIST was tested against other alignment tools using relevant query sequences derived from the D. melanogaster and Mus musculus (mouse) genomes. Real and simulated query sequences were also comparatively inquired, revealing that Genome ARTIST is a very robust solution for mapping transposon insertions. CONCLUSIONS: Genome ARTIST is a stand-alone user-friendly application, designed for high-accuracy mapping of transposon insertions and self-insertions. The tool is also useful for routine aligning assessments like detection of SNPs or checking the specificity of primers and probes. Genome ARTIST is an open source software and is available for download at www.genomeartist.ro and at GitHub (https://github.com/genomeartist/genomeartist ). PMID- 26855676 TI - Alternatives to the 'water oxidation pathway' of biological ozone formation. AB - Recent studies have shown that ozone (O3) is endogenously generated in living tissues, where it makes both positive and negative physiological contributions. A pathway for the formation of both O3 and hydrogen peroxide (H2O2) was previously proposed, beginning with the antibody or amino acid-catalyzed oxidation of water by singlet oxygen ((1)O2) to form hydrogen trioxide (H2O3) as a key intermediate. A key pillar of this hypothesis is that some of the H2O2 molecules incorporate water-derived oxygen atoms. However, H2O3 decomposes extremely readily in water to form (1)O2 and water, rather than O3 and H2O2. This article highlights key literature indicating that the oxidation of organic molecules such as the amino acids methionine, tryptophan, histidine, and cysteine by (1)O2 is involved in ozone formation. Based on this, an alternative hypothesis for ozone formation is developed involving a further reaction of singlet oxygen with various oxidized organic intermediates. H2O2 having water-derived oxygen atoms is subsequently formed during ozone decomposition in water by known reactions. PMID- 26855677 TI - An initial top-down proteomic analysis of the standard cuprizone mouse model of multiple sclerosis. AB - An initial proteomic analysis of the cuprizone mouse model to characterise the breadth of toxicity by assessing cortex, skeletal muscle, spleen and peripheral blood mononuclear cells. Cuprizone treated vs. control mice for an initial characterisation. Select tissues from each group were pooled, analysed in triplicate using two-dimensional gel electrophoresis (2DE) and deep imaging and altered protein species identified using liquid chromatography tandem mass spectrometry (LC/MS/MS). Forty-three proteins were found to be uniquely detectable or undetectable in the cuprizone treatment group across the tissues analysed. Protein species identified in the cortex may potentially be linked to axonal damage in this model, and those in the spleen and peripheral blood mononuclear cells to the minimal peripheral immune cell infiltration into the central nervous system during cuprizone mediated demyelination. Primary oligodendrocytosis has been observed in type III lesions in multiple sclerosis. However, the underlying mechanisms are poorly understood. Cuprizone treatment results in oligodendrocyte apoptosis and secondary demyelination. This initial analysis identified proteins likely related to axonal damage; these may link primary oligodendrocytosis and secondary axonal damage. Furthermore, this appears to be the first study of the cuprizone model to also identify alterations in the proteomes of skeletal muscle, spleen and peripheral blood mononuclear cells. Notably, protein disulphide isomerase was not detected in the cuprizone cohort; its absence has been linked to reduced major histocompatibility class I assembly and reduced antigen presentation. Overall, the results suggest that, like experimental autoimmune encephalomyelitis, results from the standard cuprizone model should be carefully considered relative to clinical multiple sclerosis. PMID- 26855678 TI - Theoretical study of electron transfer process between fullerenes and neurotransmitters; acetylcholine, dopamine, serotonin and epinephrine in nanostructures [neurotransmitters].C n complexes. AB - Neurotransmitters are the compounds which allow the transmission of signals from one neuron to the next across synapses. They are the brain chemicals that communicate information throughout brain and body. Fullerenes are a family of carbonallotropes, molecules composed entirely of carbon, that take the forms of spheres, ellipsoids, and cylinders. Various empty carbon fullerenes (Cn) with different carbon atoms have been obtained and investigated. Topological indices have been successfully used to construct effective and useful mathematical methods to establish clear relationships between structural data and the physical properties of these materials. In this study, the number of carbon atoms in the fullerenes was used as an index to establish a relationship between the structures of neurotransmitters (NTs) acetylcholine (AC) 1, dopamine (DP) 2, serotonin (SE) 3, and epinephrine (EP) 4 as the well-known redox systems and fullerenes C n (n = 60, 70, 76, 82, and 86) which create [NT].Cn; A-1 to A-5 up to D-1 to D-5. The relationship between the number of carbon atoms and the free energy of electron transfer (DeltaG et(n); n = 1-4) is assessed using the Rehm Weller equation for A-1 to A-5 up to D-1 to D-5 supramolecular [NT].Cn complexes. The calculations are presented for the four reduction potentials ( (Red.) E 1 to (Red.) E 4 ) of fullerenes C n . The results were used to calculate the four free energy values of electron transfer (DeltaG et(1) to DeltaG et(4)) of the supramolecular complexes A-1 to A-8 up to D-1 to D-8 for fullerenes C60 to C120. The first to fourth free activation energy values of electron transfer and the maximum wavelength of the electron transfers, DeltaG (#) et(n) and lambda et (n = 1-4), respectively, were also calculated in this study for A-1 to A-8 up to D-1 to D-8 in accordance with the Marcus theory. PMID- 26855679 TI - Synthesis, antibacterial studies, and molecular modeling studies of 3,4 dihydropyrimidinone compounds. AB - The syntheses of dihydropyrimidinones (DHPMs) using solvent-free grindstone chemistry method. All the synthesized compounds exhibited significant activity against pathogenic bacteria. The current effort has been developed to obtain new DHPM derivatives that focus on the bacterial ribosomal A site RNA as a drug target. Molecular docking simulation analysis was applied to confirm the target specificity of DHPMs. The crystal structure of bacterial 16S rRNA and human 40S rRNA was taken as receptors for docking. Finally, the docking score, binding site interaction analysis revealed that DHPMs exhibit more specificity towards 16S rRNA than known antibiotic amikacin. Accordingly, targeting the bacterial ribosomal A site RNA with potential drug leads promises to overcome the bacterial drug resistance. Even though, anti-neoplastic activities of DHPMs were also predicted through prediction of activity spectra for substances (PASS) tool. Further, the results establish that the DHPMs can serve as perfect leads against bacterial drug resistance. PMID- 26855681 TI - JOCB Bulletin. PMID- 26855680 TI - Combination of siRNA-directed gene silencing with epigallocatechin-3-gallate (EGCG) reverses drug resistance in human breast cancer cells. AB - Elevated expression of NF-E2-related factor 2 (Nrf2), a nuclear transcription factor, is a frequent genetic abnormality seen in this malignancy and is an important contributor to chemoresistance in cancer therapy. In the present study, we investigated if Nrf2 was associated with drug resistance in tamoxifen resistant MCF-7 (MCF-7/TAM) cells, and whether EGCG, major flavonoid isolated from green tea, could reverse drug resistance in MCF-7/TAM cells. Our results showed that the endogenous expression of Nrf2 as well as its target proteins heme oxygenase-1, NADP (H):quinone oxidoreductase in MCF-7/TAM cells was higher than that in MCF-7 cells. Epicatechin gallate (EGCG) significantly sensitizes MCF 7/TAM cells to tamoxifen and dramatically reduced Nrf2 expression at both the messenger RNA and protein, leading to a reduction of Nrf2-downstream genes. In addition, using siRNA technique, we found that the intracellular Nrf2 protein level was significantly decreased in MCF-7/TAM cells and tamoxifen resistance was partially reversed by Nrf2 siRNA. Combination of siRNA-directed gene silencing with EGCG downregulated the Nrf2-dependent response and partly reversed tamoxifen resistance in MCF-7/TAM cells in a synergic manner. These results suggested that combining the chemotherapeutic effect of EGCG with siRNA-mediated Nrf2 knock-down results in the feasibility of using Nrf2 inhibitors to increase efficacy of chemotherapeutic drugs. PMID- 26855682 TI - Mavoglurant in adolescents with fragile X syndrome: analysis of Clinical Global Impression-Improvement source data from a double-blind therapeutic study followed by an open-label, long-term extension study. AB - BACKGROUND: A phase II randomized, placebo-controlled, double-blind study and subsequent open-label extension study evaluated the efficacy, safety, and tolerability of mavoglurant (AFQ056), a selective metabotropic glutamate receptor subtype-5 antagonist, in treating behavioral symptoms in adolescent patients with fragile X syndrome (FXS). A novel method was applied to analyze changes in symptom domains in patients with FXS using the narratives associated with the clinician-rated Clinical Global Impression-Improvement (CGI-I) scale. METHODS: In the core study, patients were randomized to receive mavoglurant (25, 50, or 100 mg BID) or placebo over 12 weeks. In the extension, patients received 100 mg BID mavoglurant (or the highest tolerated dose) for up to 32 months. Global improvement, as a measure of treatment response, was assessed using the CGI-I scale. Investigators assigning CGI-I scores of 1 (very much improved), 2 (much improved), 6 (much worse), or 7 (very much worse) were provided a standard narrative template to collect further information about the changes observed in patients. Investigator feedback was coded and clustered into categories of improvement or worsening to identify potential areas of improvement with mavoglurant. Treatment effect in each category was characterized using the Cochran-Mantel-Haenszel test. RESULTS: A total of 134 and 103 patients had reached 2 weeks or more of core and extension study treatment, respectively, by the pre-assigned cutoff date for investigator feedback. In the core study, 34 CGI I scores of 1 or 2 were reported in 28 patients; one patient scored 6. Analysis of the CGI-I narratives did not indicate greater treatment response in patients receiving mavoglurant compared with placebo in any specific improvement domain. There were 54 CGI-I scores of 1 or 2 in 47 patients in the extension study. The most frequently reported categories of improvement were behavior and mood (79.3 and 76.6 % in core and extension studies, respectively), engagement (75.9 and 78.7 %), and communication (69.0 and 61.7 %). CONCLUSIONS: A method was established to capture and categorize FXS symptoms using CGI-I narratives. Although this method did not show benefit of drug over placebo, narratives from investigators were mostly based on parental report and thus do not represent a completely objective alternative assessment. TRIAL REGISTRATION: The studies described are registered at ClinicalTrials.gov with clinical trial identifier numbers NCT01357239 and NCT01433354. PMID- 26855683 TI - Atypical functional connectivity in resting-state networks of individuals with 22q11.2 deletion syndrome: associations with neurocognitive and psychiatric functioning. AB - BACKGROUND: 22q11.2 deletion syndrome (22q11DS) is a neurogenetic condition associated with deficits in neuropsychological functioning and psychiatric disorders. This deletion confers a high risk for the development of psychosis, as approximately 30-45 % of individuals develop psychosis in adulthood. Previous reports of resting-state functional magnetic resonance imaging (rs-fMRI) functional connectivity patterns in 22q11DS have demonstrated that atypical connectivity is associated with both the emergence and severity of psychotic symptoms. However, due to sample overlap and large age ranges of samples spanning multiple critical periods of brain maturation, more independent studies with samples within the window of time when psychotic symptoms have been shown to emerge (ages 17-26) are needed. Resting-state networks (RSNs) in 22q11DS during this stage of brain development may thus provide insight into the dynamic changes in functional integration that influence the incidence of prodromal symptoms and neurocognitive deficits characteristic of this syndrome. METHODS: Independent component analysis (ICA) was performed to identify RSNs in a combined sample of 55 individuals with 22q11DS (27 males; age range 17-26) and 29 controls (17 males; age range 17-23, consisting of 8 siblings without the deletion and 21 typically developed individuals) from two research sites. We conducted a full factorial analysis to determine group differences between 22q11DS and controls. A Poisson regression analysis was conducted in the 22q11DS group to determine relationships of rs-fMRI network connectivity with psychiatric symptoms based on factors of the 18-item Brief Psychiatric Rating Scale. Nonparametric Spearman correlations were performed to test associations between within-network functional connectivity (FC) and performance on measures of verbal memory (California Verbal Learning Test) and executive function (Behavior Rating Inventory of Executive Function Adult version) in 22q11DS. RESULTS: Between-group network connectivity analyses revealed significant differences in 9 RSNs. Decreased network FC in 22q11DS was observed in the following networks: high level visual processing network (HLVPN), low-level visual processing network (LLVPN), visual/precuneus network, left frontal-parietal network (LFPN), right frontal-parietal network (RFPN), and self-referential network (SRN). In contrast, greater network FC in 22q11DS was observed in subclusters of the LLVPN, visual/precuneus network, limbic network (LN), default mode network (DMN), and visuospatial processing network (VSPN). Increased functional connectivity of the right cuneus (visual/precuneus network) and right superior parietal lobule (DMN) in 22q11DS was positively associated with both thought disturbance and disorganization factors of the Brief Psychiatric Rating Scale (BPRS). Decreased functional connectivity in the left posterior cingulate (LLVPN) was associated with higher thought disturbance scores in 22q11DS. No associations with our neurocognitive measures passed correction for multiple comparisons (Bonferroni corrected p <= 0.0014). CONCLUSIONS: Our findings suggest that atypical network connectivity within RSNs may be indicative of increased risk for developing psychosis and supports the utility of RSNs as biomarkers of prodromal symptoms in 22q11DS. PMID- 26855685 TI - Continuous Fermentation of Wheat Straw Hydrolysate by Clostridium tyrobutyricum with In-Situ Acids Removal. AB - The present study focused on fermentative butyric acid production by Clostridium tyrobutyricum from pre-treated and hydrolysed wheat straw (PHWS) based on continuous operation mode and in situ acids extraction by reverse electro enhanced dialysis (REED). Different dilutions of PHWS in a synthetic medium (60 100 % v/v) were tested. It was found that continuous fermentation of PHWS greatly enhanced the sugar consumption rates and butyric acid productivity compared to batch tests, while application of REED enhanced them even further. Specifically, applying combined continuous operation mode and REED system for the fermentation of 70 % PHWS resulted in 19- and 53-fold higher glucose (1.37 g L-1 h-1) and xylose (0.80 g L-1 h-1) consumption rates, respectively, compared to those obtained by batch processing. Fermentation of 100 % PHWS continued unhindered with just urea and K2HPO4 added with butyric acid production rate, yield and selectivity being 1.30 g L-1 h-1, 0.45 g g-1 sugars and 0.88 g g-1 acids, respectively. These results were also confirmed in a 20 L pilot plant bioreactor system. PMID- 26855684 TI - Reciprocal changes in DNA methylation and hydroxymethylation and a broad repressive epigenetic switch characterize FMR1 transcriptional silencing in fragile X syndrome. AB - BACKGROUND: Fragile X syndrome (FXS) is the most common form of inherited intellectual disability, resulting from the loss of function of the fragile X mental retardation 1 (FMR1) gene. The molecular pathways associated with FMR1 epigenetic silencing are still elusive, and their characterization may enhance the discovery of novel therapeutic targets as well as the development of novel clinical biomarkers for disease status. RESULTS: We have deployed customized epigenomic profiling assays to comprehensively map the FMR1 locus chromatin landscape in peripheral mononuclear blood cells (PBMCs) from eight FXS patients and in fibroblast cell lines derived from three FXS patient. Deoxyribonucleic acid (DNA) methylation (5-methylcytosine (5mC)) and hydroxymethylation (5 hydroxymethylcytosine (5hmC)) profiling using methylated DNA immunoprecipitation (MeDIP) combined with a custom FMR1 microarray identifies novel regions of DNA (hydroxy)methylation changes within the FMR1 gene body as well as in proximal flanking regions. At the region surrounding the FMR1 transcriptional start sites, increased levels of 5mC were associated to reciprocal changes in 5hmC, representing a novel molecular feature of FXS disease. Locus-specific validation of FMR1 5mC and 5hmC changes highlighted inter-individual differences that may account for the expected DNA methylation mosaicism observed at the FMR1 locus in FXS patients. Chromatin immunoprecipitation (ChIP) profiling of FMR1 histone modifications, together with 5mC/5hmC and gene expression analyses, support a functional relationship between 5hmC levels and FMR1 transcriptional activation and reveal cell-type specific differences in FMR1 epigenetic regulation. Furthermore, whilst 5mC FMR1 levels positively correlated with FXS disease severity (clinical scores of aberrant behavior), our data reveal for the first time an inverse correlation between 5hmC FMR1 levels and FXS disease severity. CONCLUSIONS: We identify novel, cell-type specific, regions of FMR1 epigenetic changes in FXS patient cells, providing new insights into the molecular mechanisms of FXS. We propose that the combined measurement of 5mC and 5hmC at selected regions of the FMR1 locus may significantly enhance FXS clinical diagnostics and patient stratification. PMID- 26855686 TI - The status of glucocorticoid-induced leucine zipper protein in the salivary glands in Sjogren's syndrome: predictive and prognostic potentials. AB - BACKGROUND: We recently showed that an imbalance between the pro-inflammatory cytokine, interleukin (IL)-17, and the developmental endothelial locus-1 (Del-1) likely contributes to inflammation and salivary gland abnormalities in Sjogren's syndrome (SS). The glucocorticoid-induced leucine zipper (GILZ) protein is a pivotal player in mediating the anti-inflammatory effects of glucocorticoids. However, its status and role in salivary gland inflammation and dysfunction in SS are not established. Thus, we tested the hypothesis that SS is associated with reduced GILZ expression, thereby contributing to Del-1/Il-17 imbalance and inflammation in salivary glands. METHODS: We utilized the nonobese diabetic (NOD) mice, a model of SS-like disease as well as lower-lip biopsy samples of subjects without or with a diagnosis of SS in association with immunostaining studies. These studies were complemented with in vitro and flow-cytometry studies whereby interleukin (IL)-23-treated salivary gland cells were co-cultured with GILZ expressing cells or control cells; IL-23 is known to increase generation of IL 17. RESULTS: Salivary glands of NOD mice displayed marked leukocyte infiltration and reduced GILZ expression in association with increased IL-17 but decreased Del 1 expression. A similar pattern was observed for lower-lip biopsy samples of SS than non-SS subjects. Further, IL-23-treated salivary gland cells displayed marked increase in IL-17 but reduced Del-1 positive cells which were reversed with co-culturing with GILZ-expressing cells but not control cells. Collectively, the results are suggestive of dysregulation of GILZ playing a role in inflammation and associated Del-1/Il-17 imbalance in SS. CONCLUSIONS: Complementing our demonstration of Del-1/IL-17 imbalance in salivary glands in SS, the present study has established the relevance and significance of GILZ as a novel predictive and prognostic molecular fingerprint for SS. Thus, assessment of minor salivary gland GILZ expression, in conjunction with Del-1/IL-17 imbalance, could potentially offer a more sensitive approach to help with diagnosis of SS, at early stage of the disease, than that based on leukocyte infiltration. Future studies should establish whether treatment with GILZ ameliorates signs and symptoms of salivary malfunction of SS for which effective treatment options remain elusive. PMID- 26855688 TI - Modeling of Soft Tissues Interacting with Fluid (Blood or Air) Using the Immersed Finite Element Method. AB - This paper presents some biomedical applications that involve fluid-structure interactions which are simulated using the Immersed Finite Element Method (IFEM). Here, we first review the original and enhanced IFEM methods that are suitable to model incompressible or compressible fluid that can have densities that are significantly lower than the solid, such as air. Then, three biomedical applications are studied using the IFEM. Each of the applications may require a specific set of IFEM formulation for its respective numerical stability and accuracy due to the disparities between the fluid and the solid. We show that these biomedical applications require a fully-coupled and stable numerical technique in order to produce meaningful results. PMID- 26855687 TI - Targeting CXCL13 During Neuroinflammation. AB - The chemokine, C-X-C motif ligand 13 (CXCL13), is constitutively expressed in lymphoid organs and controls the recruitment and compartmentalization of lymphocytes and antigen presenting cells within these specialized structures. Recent data, however, also find induction of this molecule during central nervous system (CNS) inflammation under a variety of circumstances. While its role(s) in the pathogenesis of neoplastic, infectious and autoimmune disorders of the CNS remain incompletely understood, several lines of evidence suggest that CXCL13 could become a relevant therapeutic target in at least some of these diseases. This review focuses on how CXCL13 contributes to the pathogenesis of selected CNS disorders involving both experimental animals and humans, paying particular attention to the issue of whether (and if so, how) blockade of this ligand or its receptor might benefit the host. Current blocking strategies largely involve the use of monoclonal antibodies, but an improved understanding of downstream signaling pathways makes small molecule inhibition a future possibility. PMID- 26855689 TI - Carbon Sequestration by Perennial Energy Crops: Is the Jury Still Out? AB - Soil organic carbon (SOC) changes associated with land conversion to energy crops are central to the debate on bioenergy and their potential carbon neutrality. Here, the experimental evidence on SOC under perennial energy crops (PECs) is synthesised to parameterise a whole systems model and to identify uncertainties and knowledge gaps determining PECs being a sink or source of greenhouse gas (GHG). For Miscanthus and willow (Salix spp.) and their analogues (switchgrass, poplar), we examine carbon (C) allocation to above- and belowground residue inputs, turnover rates and retention in the soil. A meta-analysis showed that studies on dry matter partitioning and C inputs to soils are plentiful, whilst data on turnover are rare and rely on few isotopic C tracer studies. Comprehensive studies on SOC dynamics and GHG emissions under PECs are limited and subsoil processes and C losses through leaching remain unknown. Data showed dynamic changes of gross C inputs and SOC stocks depending on stand age. C inputs and turnover can now be specifically parameterised in whole PEC system models, whilst dependencies on soil texture, moisture and temperature remain empirical. In conclusion, the annual net SOC storage change exceeds the minimum mitigation requirement (0.25 Mg C ha-1 year-1) under herbaceous and woody perennials by far (1.14 to 1.88 and 0.63 to 0.72 Mg C ha-1 year-1, respectively). However, long term time series of field data are needed to verify sustainable SOC enrichment, as the physical and chemical stabilities of SOC pools remain uncertain, although they are essential in defining the sustainability of C sequestration (half-life >25 years). PMID- 26855690 TI - Assistive Robotic Manipulation through Shared Autonomy and a Body-Machine Interface. AB - Assistive robotic manipulators have the potential to improve the lives of people with motor impairments. They can enable individuals to perform activities such as pick-and-place tasks, opening doors, pushing buttons, and can even provide assistance in personal hygiene and feeding. However, robotic arms often have more degrees of freedom (DoF) than the dimensionality of their control interface, making them challenging to use-especially for those with impaired motor abilities. Our research focuses on enabling the control of high-DoF manipulators to motor-impaired individuals for performing daily tasks. We make use of an individual's residual motion capabilities, captured through a Body-Machine Interface (BMI), to generate control signals for the robotic arm. These low dimensional controls are then utilized in a shared-control framework that shares control between the human user and robot autonomy. We evaluated the system by conducting a user study in which 6 participants performed 144 trials of a manipulation task using the BMI interface and the proposed shared-control framework. The 100% success rate on task performance demonstrates the effectiveness of the proposed system for individuals with motor impairments to control assistive robotic manipulators. PMID- 26855691 TI - Inflammasome activation in decompensated liver cirrhosis. AB - Inflammation participates in the pathogenesis of many liver diseases, including liver cirrhosis. Certain inflammatory citokines, such as interleukin (IL)-1beta and IL-18, are produced after the activation of a multiprotein complex known as the inflammasome. Activation of the inflammasome has been documented in several liver diseases, but its role in the development and progression of liver cirrhosis or the complications associated with this disease is still largely unknown. We have recently studied the impact of the inflammasome in the sterile inflammatory response that takes place in the ascitic fluid of patients with decompensated cirrhosis, providing evidence that activation of the absent in melanoma 2 (AIM2) inflammasome is an important response in these patients. Ascitic fluid-derived macrophages were able to mount a very robust AIM2-mediated response even in the absence of a priming signal, which is usually required for the full activation of all the inflammasomes. In addition, high level of inflammasome activation in these patients was associated with a higher degree of liver disease and an increased incidence of spontaneous bacterial peritonitis. These results may help explain the exacerbated inflammatory response that usually occurs in patients with decompensated cirrhosis in the absence of detectable infections. Thus, inflammasomes should be considered as possible therapeutic targets in sterile inflammatory complications in patients with cirrhosis. PMID- 26855693 TI - Total hepatectomy and liver transplantation as a two-stage procedure for fulminant hepatic failure: A safe procedure in exceptional circumstances. AB - AIM: To evaluate the outcomes of two-stage liver transplant at a single institution, between 1993 and March 2015. METHODS: We reviewed our institutional experience with emergency hepatectomy followed by transplantation for fulminant liver failure over a twenty-year period. A retrospective review of a prospectively maintained liver transplant database was undertaken at a national liver transplant centre. Demographic data, clinical presentation, preoperative investigations, cardiocirculatory parameters, operative and postoperative data were recorded. RESULTS: In the study period, six two-stage liver transplants were undertaken. Indications for transplantation included acute paracetamol poisoning (n = 3), fulminant hepatitis A (n = 1), trauma (n = 1) and exertional heat stroke (n = 1). Anhepatic time ranged from 330 to 2640 min. All patients demonstrated systemic inflammatory response syndrome in the first post-operative week and the incidence of sepsis was high at 50%. There was one mortality, secondary to cardiac arrest 12 h following re-perfusion. Two patients required re transplantation secondary to arterial thrombosis. At a median follow-up of 112 mo, 5 of 6 patients are alive and without evidence of graft dysfunciton. CONCLUSION: Two-stage liver transplantation represents a safe and potentially life-saving treatment for carefully selected exceptional cases of fulminant hepatic failure. PMID- 26855692 TI - Lack of hepcidin expression attenuates steatosis and causes fibrosis in the liver. AB - AIM: To investigate the role of key iron-regulatory protein, hepcidin in non alcoholic fatty liver disease (NAFLD). METHODS: Hepcidin (Hamp1) knockout and floxed control mice were administered a high fat and high sucrose (HFS) or a regular control diet for 3 or 7 mo. Steatosis, triglycerides, fibrosis, protein and gene expression in mice livers were determined by histological and biochemical techniques, western blotting and real-time polymerase chain reaction. RESULTS: Knockout mice exhibited hepatic iron accumulation. Despite similar weight gains, HFS feeding induced hepatomegaly in floxed, but not knockout, mice. The livers of floxed mice exhibited higher levels of steatosis, triglycerides and c-Jun N-terminal kinase (JNK) phosphorylation than knockout mice. In contrast, a significant increase in fibrosis was observed in knockout mice livers within 3 mo of HFS administration. The hepatic gene expression levels of sterol regulatory element-binding protein-1c and fat-specific protein-27, but not peroxisome proliferator-activated receptor-alpha or microsomal triglyceride transfer protein, were attenuated in HFS-fed knockout mice. Knockout mice fed with regular diet displayed increased carnitine palmitoyltransferase-1a and phosphoenolpyruvate carboxykinase-1 but decreased glucose-6-phosphatase expression in the liver. In summary, attenuated steatosis correlated with decreased expression of lipogenic and lipid storage genes, and JNK phosphorylation. Deletion of Hamp1 alleles per se modulated hepatic expression of beta-oxidation and gluconeogenic genes. CONCLUSION: Lack of hepcidin expression inhibits hepatic lipid accumulation and induces early development of fibrosis following high fat intake. Hepcidin and iron may play a role in the regulation of metabolic pathways in the liver, which has implications for NAFLD pathogenesis. PMID- 26855695 TI - Non-invasive evaluation of liver fibrosis by acoustic radiation force impulse and aminotransferase:platelet ratio index in chronic hepatitis C. AB - In a previous issue of the World Journal of Gastroenterology, we have read the article by Li et al with great interest. We would like to thank the authors for their comprehensive contribution. However, it is our wish to make minor criticism over the present study from the perspective of methodology. PMID- 26855696 TI - Silver Nanostructures for Fluorescence Correlation Spectroscopy: Reduced Volumes and Increased Signal Intensities. AB - Fluorescence correlation spectroscopy (FCS) is a widely used technique to investigate the interactions and dynamics of molecules, below micromolar concentrations. Silver nanostructure (AgNS) substrates can extend the applicability of FCS to higher concentrations, which is useful for many biologically relevant reactions. Additionally, these substrates can improve detection efficiency by increasing fluorescence signal intensities. The ease of preparation of the AgNS substrates in comparison to previously investigated materials prepared by top-down nanofabrication is expected to make them readily available and suitable for various FCS applications. PMID- 26855697 TI - Evaluation of diagnostic accuracy and dimensional measurements by using CBCT in mandibular first molars. AB - BACKGROUND: This study aimed to assess the diagnostic accuracy of cone beam computed tomography (CBCT) and quantitatively evaluate the morphology of mandibular first molars using CBCT. MATERIAL AND METHODS: Twenty-four double rooted mandibular first molars were evaluated by NewTom VGi CBCT. The distance from the furcation and apex to the cementoenamel junction (CEJ), diameter and thickness of canal walls, the buccolingual (BL) to mesiodistal (MD) ratio (DeltaD), prevalence of oval canals at different sections and taper of the canals were all determined. In order to assess the diagnostic accuracy of CBCT, distance from the furcation and apex to the CEJ and thickness of canal walls at the CEJ and apex were compared with the gold standard values (caliper and stereomicroscope). Statistical analyses were carried out using intraclass correlation coefficient (ICC), paired t-test and repeated measures ANOVA. RESULTS: A high correlation existed between the CBCT and gold standard measurements (P<0.001). In dimensional measurements, length of mesial root was higher than the distal root and lingual furcation was farther from the CEJ than the buccal furcation (P<0.001). An important finding of this study was the mesiodistal taper of the mesiobuccal (MB) and mesiolingual (ML) canals; which was equal to 0.02. CONCLUSIONS: CBCT has acceptable diagnostic accuracy for measurement of canal wall thickness. Cleaning and shaping of the canals should be performed based on the unique anatomy of the respective canal; which necessitates the use of advanced imaging techniques for thorough assessment of root canal anatomy in a clinical setting. KEY WORDS: Permanent mandibular first molar, accuracy, cone-beam computed tomography, dimensional measurement. PMID- 26855698 TI - Langerhans cell histiocytosis: Current concepts in dentistry and case report. AB - Langerhans cell histiocytosis (LCH), which is a rare granulomatous pediatric disease of unknown etiology, is characterized by the idiopathic proliferation and accumulation of abnormal and clonal Langerhans cells or their marrow precursors, resulting in localized, solitary or multiple destructive lesions. These lesions are most commonly eosinophilic granuloma, which are found in craniofacial bone structures such as the skull and mandible, skin and other organs. In children, the disease has a variable initial presentation, and the clinical course, prognosis and survival are unpredictable. The aims of this report were to present an LCH case in a girl aged 2 years, 8 months and her clinicopathological features, to describe the bucodental management provided, and to discuss special dental considerations of this disease. KEY WORDS: Children, dental management, histiocytosis, Langerhans cells. PMID- 26855699 TI - Orthodontically guided bone transport in the treatment of alveolar cleft: A case report. AB - INTRODUCTION: Conventional treatments are sometimes not possible in certain alveolar cleft cases due to the severity of the gap which separates the fragments. Various management strategies have been proposed, including sequential surgical interventions or delaying treatment until adulthood to then carry out maxillary osteotomies. A further alternative approach has also been proposed, involving the application of bone transport techniques to mobilise the osseous fragments and thereby reduce the gap between lateral fragments and the premaxilla. CASE REPORT: We introduce the case of a 10-year-old patient who presented with a bilateral alveolar cleft and a severe gap. Stable occlusion between the premaxilla and the mandible was achieved following orthodontic treatment, making it inadvisable to perform a retrusive osteotomy of the premaxilla in order to close the alveolar clefts. Faced with this situation, it was decided we would employ a bone transport technique under orthodontic guidance using a dental splint. This would enable an osseous disc to be displaced towards the medial area and reduce the interfragmentary distance. During a second surgical intervention, closure of the soft tissues was performed and the gap was filled in using autogenous bone. CONCLUSIONS: The use of bone transport techniques in selected cases allows closure of the osseous defect, whilst also preserving soft tissues and reducing the amount of bone autograft required. In our case, we were able to respect the position of the premaxilla and, at the same time, generate new tissues at both an alveolar bone and soft tissue level with results which have remained stable over the course of time. KEY WORDS: Alveolar cleft, bone transport, graft. PMID- 26855700 TI - Effect of indirect composite treatment microtensile bond strength of self adhesive resin cements. AB - BACKGROUND: No specific indications about the pre-treatment of indirect composite restorations is provided by the manufacturers of most self-adhesive resin cements. The potential effect of silane treatment to the bond strength of the complete tooth/indirect restoration complex is not available.The aim of this study was to determine the contribution of different surface treatments on microtensile bond strength of composite overlays to dentin using several self adhesive resin cements and a total-etch one. MATERIAL AND METHODS: Composite overlays were fabricated and bonding surfaces were airborne-particle abraded and randomly assigned to two different surface treatments: no treatment or silane application (RelyX Ceramic Primer) followed by an adhesive (Adper Scotchbond 1 XT). Composite overlays were luted to flat dentin surfaces using the following self-adhesive resin cements: RelyX Unicem, G-Cem, Speedcem, Maxcem Elite or Smartcem2, and the total-etch resin cement RelyX ARC. After 24 h, bonded specimens were cut into sticks 1 mm thick and stressed in tension until failure. Two-way ANOVA and SNK tests were applied at alpha=0.05. RESULTS: Bond strength values were significantly influenced by the resin cement used (p<0.001). However, composite surface treatment and the interaction between the resin cement applied and surface treatment did not significantly affect dentin bond strength (p>0.05). All self-adhesive resin cements showed lower bond strength values than the total etch RelyX ARC. Among self-adhesive resin cements, RelyX Unicem and G-Cem attained statistically higher bond strength values. Smartcem2 and Maxcem Elite exhibited 80-90% of pre-test failures. CONCLUSIONS: The silane and adhesive application after indirect resin composite sandblasting did not improve the bond strength of dentin-composite overlay complex. Selection of the resin cement seems to be a more relevant factor when bonding indirect composites to dentin than its surface treatment. KEY WORDS: Bond strength, self-adhesive cement, silane, dentin, indirect composite. PMID- 26855694 TI - Portal hypertensive gastropathy: A systematic review of the pathophysiology, clinical presentation, natural history and therapy. AB - AIM: To describe the pathophysiology, clinical presentation, natural history, and therapy of portal hypertensive gastropathy (PHG) based on a systematic literature review. METHODS: Computerized search of the literature was performed via PubMed using the following medical subject headings or keywords: "portal" and "gastropathy"; or "portal" and "hypertensive"; or "congestive" and "gastropathy"; or "congestive" and "gastroenteropathy". The following criteria were applied for study inclusion: Publication in peer-reviewed journals, and publication since 1980. Articles were independently evaluated by each author and selected for inclusion by consensus after discussion based on the following criteria: Well designed, prospective trials; recent studies; large study populations; and study emphasis on PHG. RESULTS: PHG is diagnosed by characteristic endoscopic findings of small polygonal areas of variable erythema surrounded by a pale, reticular border in a mosaic pattern in the gastric fundus/body in a patient with cirrhotic or non-cirrhotic portal hypertension. Histologic findings include capillary and venule dilatation, congestion, and tortuosity, without vascular fibrin thrombi or inflammatory cells in gastric submucosa. PHG is differentiated from gastric antral vascular ectasia by a different endoscopic appearance. The etiology of PHG is inadequately understood. Portal hypertension is necessary but insufficient to develop PHG because many patients have portal hypertension without PHG. PHG increases in frequency with more severe portal hypertension, advanced liver disease, longer liver disease duration, presence of esophageal varices, and endoscopic variceal obliteration. PHG pathogenesis is related to a hyperdynamic circulation, induced by portal hypertension, characterized by increased intrahepatic resistance to flow, increased splanchnic flow, increased total gastric flow, and most likely decreased gastric mucosal flow. Gastric mucosa in PHG shows increased susceptibility to gastrotoxic chemicals and poor wound healing. Nitrous oxide, free radicals, tumor necrosis factor-alpha, and glucagon may contribute to PHG development. Acute and chronic gastrointestinal bleeding are the only clinical complications. Bleeding is typically mild-to-moderate. Endoscopic therapy is rarely useful because the bleeding is typically diffuse. Acute bleeding is primarily treated with octreotide, often with concomitant proton pump inhibitor therapy, or secondarily treated with vasopressin or terlipressin. Nonselective beta-adrenergic receptor antagonists, particularly propranolol, are used to prevent bleeding after an acute episode or for chronic bleeding. Iron deficiency anemia from chronic bleeding may require iron replacement therapy. Transjugular-intrahepatic-portosystemic-shunt and liver transplantation are highly successful ultimate therapies because they reduce the underlying portal hypertension. CONCLUSION: PHG is important to recognize in patients with cirrhotic or non-cirrhotic portal hypertension because it can cause acute or chronic GI bleeding that often requires pharmacologic therapy. PMID- 26855701 TI - The effects of silver nanoparticles on antimicrobial activity of ProRoot mineral trioxide aggregate (MTA) and calcium enriched mixture (CEM). AB - BACKGROUND: Although, mineral trioxide aggregate (MTA) and new experimental cement (CEM) are good root filling cements, but had no or low antimicrobial activities. The aim of this study was to evaluate the effects of addition of silver nanoparticles (SNP) to these two cements on antimicrobial effects against five most dental infection related microorganisms. MATERIAL AND METHODS: Two suspensions of 100 and 200 ppm of SNP were prepared and 180 MUl of microbial suspension with 1.5 * 108 CFU/ml of each respected microorganisms were re suspended in deionized water or each of SNP suspensions. After that, 60 MUg of MTA and CEM were added to each tube. In one tube, the mixture of all above mentioned microorganisms were added as a source of microorganism. Colonies were counted after 0, 24, 48, 72 and 96 hours intervals of incubation at 35 degrees C on blood agar for evaluation of antimicrobial efficacy. RESULTS: MTA and CEM had antibacterial activities on all microorganisms' strains except for Enterococcus faecalis and mixture group. MTA had better antibacterial activity than CEM but the difference was not significant (p<0.05). The combination of SNP with two cements resulted in significantly higher antimicrobial activities (p<0.05). Also, there was no statistically significant difference between two SNP concentrations (p>0.05). CONCLUSIONS: Mixture of MTA and CEM with different concentrations of SNP significantly increased the antibacterial activity. KEY WORDS: Mineral trioxide aggregate, calcium-enriched mixture, silver nanoparticle, antimicrobial activity. PMID- 26855702 TI - Microscopic assessment of the sealing ability of three endodontic filling techniques. AB - BACKGROUND: Several techniques have been proposed for root canal filling. New rotary files, with non-standardized taper, are appearing, so, points adapted to the taper of the last instrument used to prepare the canal can help in the obturation process. The aim of this study is to assess the sealing ability of different root canal filling techniques. MATERIAL AND METHODS: Root canals from 30 teeth were shaped with Mtwo and divided in three groups; A, standard lateral condensation with size 35 and 20 gutta-percha points; B, standard lateral condensation and injected gutta-percha; C, single gutta-percha point (standardized 35 Mtwo), continuous wave technique and injected gutta-percha. Root surfaces were covered with nail varnish, except for the apical 2 mm, and submerged in a NO3Ag2 solution; apical stain penetration was measured in mm. Data were compared using the Kruskal-Wallis test with a 90% confidence interval. RESULTS: A and B groups showed stain leakage in the 90% of the cases, whereas it was of 80% for group C. Stain leakage intervals were 1-5 mm for groups A and B and 1-3 mm for group C. There were no statistically significant differences between the three studied groups (p>.05). CONCLUSIONS: All the analyzed root canal filling techniques showed some apical stain leakage, without significant differences among them. KEY WORDS: Gutta-percha filling, microleakage, single cone, injected gutta-percha, warm gutta-percha. PMID- 26855703 TI - Periodontal treatment needs and systemic diseases in an older population in Greece. AB - BACKGROUND: To evaluate the relationship between systemic diseases, body mass index and periodontal treatment needs in an older population in Greece. MATERIAL AND METHODS: A total of 262 older people were clinically examined about their periodontal status and medical histories were recorded using a health history questionnaire. Additionally, weight and height measurements as well as demographic data were obtained from the participants in the study. RESULTS: Older people exhibited mean age of 63.98 years, weight of 78.76 kg and height of 1.64 m. The mean CPITN score was 2.84. 31.7% of the study population were smokers and 53.8% females. No statistically significant difference was observed in seniors between periodontal treatment needs and systemic diseases. Females exhibited statistically significant more often osteoporosis, thyroid disorders (p<0.001) and hypercholesterolemia (p=0.014) than males. High CPTIN scores were not associated with higher levels of BMI. CONCLUSIONS: Within the limitation of this study, older adults' periodontal treatment needs are not associated significantly with a great number of systemic diseases and body mass index. KEY WORDS: Seniors, periodontitis, systemic diseases, body mass index (BMI), smoking, Greece. PMID- 26855704 TI - Shear bond strength and debonding characteristics of metal and ceramic brackets bonded with conventional acid-etch and self-etch primer systems: An in-vivo study. AB - BACKGROUND: Different in-vitro studies have reported various results regarding shear bond strength (SBS) of orthodontic brackets when SEP technique is compared to conventional system. This in-vivo study was designed to compare the effect of conventional acid-etching and self-etching primer adhesive (SEP) systems on SBS and debonding characteristics of metal and ceramic orthodontic brackets. MATERIAL AND METHODS: 120 intact first maxillary and mandibular premolars of 30 orthodontic patients were selected and bonded with metal and ceramic brackets using conventional acid-etch or self-etch primer system. The bonded brackets were incorporated into the wire during the study period to simulate the real orthodontic treatment condition. The teeth were extracted and debonded after 30 days. The SBS, debonding characteristics and adhesive remnant indices (ARI) were determined in all groups. RESULTS: The mean SBS of metal brackets was 10.63+/ 1.42 MPa in conventional and 9.38+/-1.53 MPa in SEP system, (P=0.004). No statistically significant difference was noted between conventional and SEP systems in ceramic brackets. The frequency of 1, 2 and 3 ARI scores and debonding within the adhesive were the most common among all groups. No statistically significant difference was observed regarding ARI or failure mode of debonded specimens in different brackets or bonding systems. CONCLUSIONS: The SBS of metal brackets bonded using conventional system was significantly higher than SEP system, although the SBS of SEP system was clinically acceptable. No significant difference was found between conventional and SEP systems used with ceramic brackets. Total SBS of metal brackets was significantly higher than ceramic brackets. Due to adequate SBS of SEP system in bonding the metal brackets, it can be used as an alternative for conventional system. KEY WORDS: Shear bond strength, Orthodontic brackets, Adhesive remnant index, self-etch. PMID- 26855705 TI - Fracture resistance of tooth restored with four glass fiber post systems of varying surface geometries-An in vitro study. AB - BACKGROUND: The purpose of this study was to relate the fracture resistance of endodontically treated teeth in relation to post geometry. MATERIAL AND METHODS: Forty single rooted mandibular premolars were instrumented by step - back technique and obturated by lateral condensation. Forty teeth were randomly divided into four groups: Reforpost glass fiber X-ray(r), RelyX(r), Exacto conical(r) and Parapost Fiber Lux(r). The post spaces were prepared using respective drills and luted. The core build up was done and metal crowns were luted. Fracture resistance was determined in universal testing machine. The statistical analysis was done using one way ANOVA and post hoc Tukey Kramer test. RESULTS: The teeth restored with Reforpost showed highest fracture resistance followed by Parapost and Exacto conical. The teeth restored with RelyX showed least fracture resistance. The teeth restored with Parapost had less unfavourable fracture followed by exacto conical. CONCLUSIONS: Parallel design had less number of catastrophic failure and had better fracture resistance. KEY WORDS: Fracture resistance, glass fiber post, post geometry, stress. PMID- 26855706 TI - Age and gender correlation of gonial angle, ramus height and bigonial width in dentate subjects in a dental school in Far North Queensland. AB - BACKGROUND: This study aimed to determine if mandibular parameters (gonial angle, bigonial width and ramus height) measured from panoramic radiographs, can be used to determine a correlation with an individual's age and gender in dentate subjects in Far North Queensland. MATERIAL AND METHODS: The study utilised 2699 randomly selected panoramic radiographs of patients between the ages of 19-69 years, from which 220 fulfilled the inclusion criteria. Each panoramic radiograph was analysed and the above three parameters recorded and measured. These values were collated into appropriate age and gender groups and subjected to statistical analysis. RESULTS: The mean age of the participants was 44.1+/-14.41, with males being shown to have a statistically significant larger ramus height and bigonial width than females (P<0.0001 for both). Females, on the other hand, were shown to have a significantly larger gonial angle than males (P<0.0002). General trends revealed gonial angle to increase with age, whilst bigonial width and ramus height were shown to decrease with age. CONCLUSIONS: The assessment of mandibular morphology through radiographic measurements may be useful in estimating an individual's age and gender when comparing to a known population standard. KEY WORDS: Bigonial width, gonial angle, panoramic radiograph, ramus height. PMID- 26855707 TI - An in vitro evaluation of the effects of desensitizing agents on microleakage of Class V cavities. AB - BACKGROUND: The aim of this study was to evaluate the effect of a desensitizing agent on microleakage of Class V cavities. MATERIAL AND METHODS: 72 premolar teeth were used. There were 6 groups. Class V restorations were prepared with two different restorative materials (Equia fil, GC, America and Grandio, VOCO, Germany) and two adhesive systems (Clearfil SE Bond, Kuraray, Japan and S3 Bond Plus, Kuraray, Japan) with and without desensitizing agent (Gluma Desensitizer, Heraeus Kulzer, Germany). Restorations were polished with aluminum oxide abrasive discs. Then a range of 5 - 55C thermocycling was performed 10.000 times. The microleakage of restorations was examined with dye penetration method (Basic fuchsine). Bonferroni corrections and Kruskal-Wallis test were used to determine the significance of differences in occlusal and gingival dye penetration scores between groups. RESULTS: There was no stastistical significance between the occlusal and gingival microleakage scores within the groups were shown. CONCLUSIONS: It can be concluded that use of desensitizing agent under both high viscosity glass ionomer restorative materials and resin composites doesn't affect the microleakage. KEY WORDS: High viscosity glass ionomer cement, composite resin, desensitizing agent, microleakage. PMID- 26855708 TI - Importance of rotary systems in dental care by undergraduate students in patients of a public health service of Belo Horizonte. AB - BACKGROUND: The aim of this study was to evaluate the fracture rates of ProTaper rotary files used in the endodontics extension clinic of the Undergraduate Dentistry Course of the Pontifical Catholic University of Minas Gerais during the prior eight years. MATERIAL AND METHODS: Control record data regarding file usage by students were collected and analyzed by semester. For each period, the total number of patient consultations, the frequency of file use, the occurrence of fractures and the file numbers for which fractures occurred were noted. Descriptive statistics, including frequency of file fractures were calculated for all file types. The chi-square test was used to evaluate differences in the frequency of file fractures between all file types. RESULTS: The study results revealed that during the examined period, there were 1006 consultations and 7993 uses of files. A total of 30 file fractures were recorded throughout this period; thus, fractures occurred in 0.37% of total file uses and 2.98% of all consultations. The most frequently used files were S1, S2 and F1, and these files also accounted for the most fractures. However, no differences in the frequency of file fractures were observed between the file types (p??0.05). CONCLUSIONS: The low fracture rates observed in this study indicate that the examined instruments can be used to safely provide dental care to patients. KEY WORDS: Dental instruments, endodontics, public health. PMID- 26855709 TI - Effectiveness of oral health education versus nicotine replacement therapy for tobacco cessation- a parallel randomized clinical trial. AB - BACKGROUND: India has millions of tobacco users. It is the leading cause of deaths due to oral cancer and hence needs effective strategies to curb it. Hence the aim of present study was to evaluate and compare the effectiveness of Oral Health Education (OHE) and Nicotine Replacement Therapy (NRT) in tobacco cessation. MATERIAL AND METHODS: The clinical trial consisted of Manohar Lal Kapoor (MLK) factory workers (n= 40) giving history of tobacco consumption (smoking/smokeless) within past 30 days. They were randomized into OHE (n=20) and NRT (n=20) groups. Baseline evaluation (demographic, smoking/ smokeless behaviour) was done. Fagerstrom test was used for Nicotine Dependence (FTND) and to assess nicotine addiction level. Follow up was done at an interval of 1week, 2 weeks, 1 month, 2 months and 3 months to assess the reduction in the mean FTND score. "Nano-CheckTM Rapid Nicotine test" was used for the qualitative detection of cotinine in human urine. Appropriate statistical analysis was performed (Paired and Unpaired t test). RESULTS: In both OHE and NRT group there was a significant reduction (p< 0.00001) in mean Fagerstrom score at every follow up but when both the groups were compared mean Fagerstrom score reduction was more in NRT than OHE at all time interval though it was not statistically significant (p>0.05). CONCLUSIONS: NRT is better than OHE when both the groups were compared. However, it was found that any intervention given to tobacco users either NRT or OHE is helpful for the patients in the process of quitting tobacco. KEY WORDS: Tobacco cessation, nicotine replacement therapy, oral health education, fagerstrom test, urine cotinine. PMID- 26855710 TI - Antimicrobial effects of Citrus sinensis peel extracts against dental caries bacteria: An in vitro study. AB - BACKGROUND: Ethnomedicine is gaining admiration since years but still there is abundant medicinal flora which is unrevealed through research. The study was conducted to assess the in vitro antimicrobial potential and also determine the minimum inhibitory concentration (MIC) of Citrus sinensis peel extracts with a view of searching a novel extract as a remedy for dental caries pathogens. MATERIAL AND METHODS: Aqueous and ethanol (cold and hot) extracts prepared from peel of Citrus sinensis were screened for in vitro antimicrobial activity against Streptococcus mutans and Lactobacillus acidophilus, using agar well diffusion method. The lowest concentration of every extract considered as the minimal inhibitory concentration (MIC) values were determined for both test organisms. One way ANOVA with Post Hoc Bonferroni test was applied for statistical analysis. Confidence level and level of significance were set at 95% and 5% respectively. RESULTS: Dental caries pathogens were inhibited most by hot ethanolic extract of Citrus sinensispeel followed by cold ethanolic extract. Aqueous extracts were effective at very high concentrations. Minimum inhibitory concentration of hot and cold ethanolic extracts of Citrus sinensis peel ranged between 12-15 mg/ml against both the dental caries pathogens. CONCLUSIONS: Citrus sinensispeels extract was found to be effective against dental caries pathogens and contain compounds with therapeutic potential. Nevertheless, clinical trials on the effect of these plants are essential before advocating large-scale therapy. KEY WORDS: Agar well diffusion, antimicrobial activity, dental caries, Streptococcus mutans, Lactobacillus acidophilus. PMID- 26855711 TI - Effectiveness of dentist's intervention in smoking cessation: A review. AB - INTRODUCTION: Smoking is one of the main public health problems in developed countries. Despite extensive evidence on the effects of smoking on both oral and general health, the rate of smoking cessation is not promising. MATERIAL AND METHODS: To review the evidence on knowledge and programs for smoking cessation developed by dentists, a literature review was carried out on programs for smoking cessation from the dentist's perspective, as well as a review of behavioral guidelines that have been recently proposed for these interventions. We used the keywords "Tobacco", "Smoking Prevention", "Public Health" AND "Dentistry", to identify controlled studies, systematic reviews and meta-analyses published between 1999 and 2014, in Google Scholar, SCOPUS and PubMed. RESULTS: Out of 177 studies found, 35 were considered, and these were divided into 2 groups of 20 and 15 articles respectively, according to type of study and inclusion criteria. CONCLUSIONS: There is considerable scientific evidence describing the programs for smoking cessation used in dentistry, which support their effectiveness. Overall, these are brief behavioral interventions complemented by pharmacological treatment, with the participation of the entire dental team. KEY WORDS: Dentistry, nicotine, smoking cessation, tobacco. PMID- 26855712 TI - Oral encapsulated vascular malformation: An undescribed presentation in the mouth. AB - Vascular lesions have been classified in two broad categories, hemangiomas and malformations. Encapsulated vascular lesions have not been reported in the oral cavity, but they were described in other sites, mainly in the orbit. Herein, we present a case of an oral encapsulated vascular lesion located in the right buccal mucosa of a 69-year-old male, including histological and immunohistochemical description and a literature review. KEY WORDS: Buccal mucosa, hemangioma, vascular malformation, oral cavity. PMID- 26855713 TI - Desmoplastic fibroblastoma (collagenous fibroma) of the oral cavity. AB - Desmoplastic fibroblastoma is benign soft tissue tumor, with fibroblastic or myofibroblastic origin, that rarely occurs in oral cavity. We reported the case of a 56-year-old man who presented a tumor in the left mandibular alveolar ridge, with slow and asymptomatic growth, with no osseous involvement. The tumor was sessile with lobulated surface, covered by healthy mucosa with erythematous areas. The lesion was excised and specimens sent to histopathology and immunohistochemistry. Histopathological exam showed a non-encapsulated fibroblastic proliferation, characterized by myofibroblasts, spindle and stellate fibroblasts with large or oval nuclei and bi or tri nucleation, immersed in an abundant hypocellular dense collagen stroma. Tumor cells were positive for vimentin, HHF35, alpha-smooth muscle actin and factor XIIIa. The diagnosis of desmoplastic fibroblastoma was based in the clinical history of absence of trauma related to the growth in the alveolar ridge, associated with macroscopic, microscopic and immunohistochemical features. The patient is free-diseases by eight months. KEY WORDS: Collagenous fibroma, desmoplastic fibroblastoma, neoplasm of connective and soft tissue. PMID- 26855714 TI - An analysis in vivo of intracanal bacterial load before and after chemo mechanical preparation: A comparative analysis of two irrigants and two activation techniques. AB - BACKGROUND: The goals of this randomized double-blind trial were to assess the antimicrobial activity in vivo of Sodium hypochlorite (NaOCl) vs. chlorhexidine gluconate (CHX) used in combination either with EndoActivator(r) or IRRI S(r) files in patients with apical periodontitis. MATERIAL AND METHODS: A total of 120 patients with apical periodontitis (in single or multiple root canals) were randomly assigned to the four irrigation protocols outlined below: Group A: 5.25% sodium hypochlorite (NaOCl) + EndoActivator(r); Group B: 5.25% NaOCl + IRRI S(r) files; Group C: 2% chlorhexidine gluconate (CHX) + EndoActivator(r); Group D: 2% CHX + IRRI S(r) files. Paper points were used to collect microbiological samples before (1A samples) and after (1B samples) irrigation. Viable colony-forming units (CFU) were quantified twice: (1) without speciation, and (2) only for Enterococcus Faecalis(EF). Statistical analysis was performed using SPSS 22.0 for Windows. RESULTS: No significant differences were observed between NaOCl and CHX in the reduction of CFU; in fact, reduction was < 93% for the two irrigants. Conversely, statistically significant differences were found between the two activation techniques (sonic and ultrasonic) in the reduction of Enterococcus Faecalis(EF). Thus, the effectiveness of ultrasonic activation was significantly higher (< 93%; p=0.012) as compared to sonic activation. Following the combination of the two irrigants with the two activation techniques (groups A, B, C and D), significant differences were observed between group A and B (p=0.025) in the reduction of EF populations, reaching up to 94%. CONCLUSIONS: NaClO and CHX are effective in reducing intracanal bacterial load. Ultrasonic activation is the most effective activation technique in reducing EF populations. KEY WORDS: Chlorhexidine gluconate, sodium hypochlorite, ultrasonic irrigation, sonic irrigation, apical periodontitis, Enterococcus faecalis. PMID- 26855715 TI - Sensory disturbances of buccal and lingual nerve by muscle compression: A case report and review of the literature. AB - INTRODUCTION: Several studies on cadavers dissection have shown that collateral branches of the trigeminal nerve cross muscle bundles on their way, being a possible etiological factor of some nerve disturbances. CASE REPORT: A 45-year old man attended to the Temporomandibular Joint and Orofacial Pain Unit of the Master of Oral Surgery and Implantology in Hospital Odontologic of Barcelona University, referring tingling in the left hemifacial region and ipsilateral lingual side for one year, with discomfort when shaving or skin compression. DISCUSSION: Several branches of the trigeminal nerve follow a path through the masticatory muscles, being the lingual nerve and buccal nerve the most involved. The hyperactivity of the muscle bundles that are crossed by nerve structures generates a compression that could explain certain orofacial neuropathies (numbness and / or pain) in which a clear etiologic factor can not be identified. KEY WORDS: Buccal nerve, paresthesia, idiopathic trigeminal sensory neuropathy. PMID- 26855716 TI - Kissing molars extraction: Case series and review of the literature. AB - Kissing molars are a very rare form of inclusion defined as molars included in the same quadrant, with occlusal surfaces contacting each other within a single dental follicle. We present four cases of this pathology: a 35 year-old male, referred to the Oral and Maxillofacial Surgery Department of the Hospital Virgen del Rocio in Seville, and three females of 24, 26, and 31 years, all of which had kissing molars that were treated by tooth extraction. We have found only 10 cases published in the medical literature in which this type of inclusion is briefly described, none of which elaborate on the surgical technique employed. In these cases, the indication for surgery is established when there is a history of recurring infections or cystic lesions associated with dental inclusions. The extraction of kissing molars requires an exhaustive comprehension of the anatomy of the region involved, sufficiently developed surgical abilities, and an extensive planning process. KEY WORDS: Impacted molar, kissing molar, surgical extraction. PMID- 26855717 TI - Primary Neuroendocrine Tumor of Liver (Rare Tumor of Liver). AB - INTRODUCTION: A neuroendocrine tumor has known as a neuroendocrine system tumor. Rarely, neuroendocrines have found in other areas, like the liver, gallbladder, bile ducts, kidneys, ovaries or testicles. CASE PRESENTATION: We have a 41-year old woman has referred to our medical center, complaining of fullness and vague pain on her right upper quadrant. The liver scan, sonography, MRI demonstrated multi lobular cysts in 6th and 7 th seg-ments of her liver and chest imaging was normal, oc-terotid scan has not shwon metastatic neuroendocrine tour of liver. CONCLUSIONS: Liver could be the location of metastatic neuroendo-crine tumors, for example metastatic carcinoid tumor. Therefore, it was so important to diffrentatiate pri-mary neuroendocrine tumor from metastatic neuro-endocrine tumors. PMID- 26855718 TI - Invasive Growth Hormone Producing Pituitary Adenoma With Lymphocytic Infiltration: A Case Report and Literature Review. AB - INTRODUCTION: We have presented a rare case of growth hormone (GH) producing pituitary adenoma with lymphocytic infiltration and brain parenchyma invasion. CASE PRESENTATION: A 37-year-old woman has presented with complaints of headache, amenorrhea and acromegalic features. Her laboratory studies showed markedly elevated levels of Insulin-like Growth Factor 1 (IGF-1), and low levels of follicle stimulating hormone and luteinizing hormone. Computerized tomography has revealed a pituitary mass without extra-sellar extension. The tumor has completely excised via trans-nasal endoscopic approach. Histologically, the tumor has diagnosed as a pituitary adenoma with GH positive cells. The serum IGF1 levels have gradually decreased to the normal range and the patient was symptom free for three and a half years when she has returned with complaint of visual impairment. The brain MRI that time has shown a supra-sellar mass growing independently into the remaining sellar part. Subsequently, surgical operation has performed via trans-nasal endoscopic approach. Histopathological and immunohistochemistry examination have revealed a rare case of growth hormone producing pituitary adenoma with brain invasion and lymphocytic infiltration. CONCLUSIONS: The aim of this publication was to present a rare case of growth hormone producing pituitary adenoma with brain invasion and lymphocytic infiltration. PMID- 26855719 TI - Individually and Combined Water-Based Exercise With Ginger Supplement, on Systemic Inflammation and Metabolic Syndrome Indices, Among the Obese Women With Breast Neoplasms. AB - BACKGROUND: Breast neoplasms has known as the most common cancer among the women worldwide, and relationship between obesity, metabolic syndrome, inflammation and cancer has been recognized since many years ago. OBJECTIVES: The aim of this study was to determine the individual and concomitant effect of 6-weeks water based exercise and oral ginger supplement on markers that have related to metabolic syndrome and systemic inflammation in obese women with breast neoplasms. PATIENTS AND METHODS: Forty women whose have diagnosed with breast neoplasms have volunteered to participate in the study. Subjects have randomly assigned into four groups; placebo, exercise training, ginger supplement and exercise training+ ginger supplement groups. Subjects in the ginger supplement group and the exercise training+ ginger supplement group have orally received 4 capsules, 7 days a week and for 6 weeks. The water-based exercise training program have collected at a progressive intensity and time, have ranged from 50% to 75% of heart rate reserve, in a pool, 4 times a week for 6 weeks. Fasting blood sampling has collected at the pretest and post-test. RESULTS: The ginger supplementation and the water-base exercise have resulted in a reduction of hs CRP, IL-10, insulin, glucose, insulin resistance, LDL-C, TG; but an increase in HDL-C and HDL-C/LDL-C. The water-base exercise and ginger supplement group have significantly shown larger positive effect in all outcomes, in comparison with the water-base exercise or ginger supplement alone groups. CONCLUSIONS: Findings have suggested that obese breast neoplasms survivors have commonly shown metabolic syndrome and elevated inflammation, which placed them at an increased risk for cardiovascular diseases. Moreover, data has indicated a protective effect of the nondrug strategies, such as water-base exercise and ginger supplementation have played an important role in pathogenesis of inflammatory and metabolic responses, among diagnosed breast neoplasms. PMID- 26855720 TI - High Prevalence of Tobacco Use and Associated Oral Mucosal Lesion Among Interstate Male Migrant Workers in Urban Kerala, India. AB - BACKGROUND: Kerala is a highly urbanized state in India and interstate migrant laborers working there forms a marginalized community. It was generally perceived that use of tobacco and alcohol was high among the workers, but there are no epidemiological studies assessing the actual burden. OBJECTIVES: To estimate the prevalence of use of tobacco and also the prevalence of oral mucosal lesions associated with such use consumption among the adult male interstate migrant workers in North Kerala. MATERIALS AND METHODS: A cross sectional study was carried out among male migrant workers above 18 years working in different factories in urban parts of Kannur district. Total of 244 participants attending routine health check-up camp were assessed for the use of tobacco/alcohol, type, frequency and duration of their use by a questionnaire. The trained dental interns conducted oral cavity examination for detecting oral mucosal lesions associated with tobacco use. RESULTS: The prevalence of current use of smoked tobacco, smokeless tobacco and alcohol use were 41.8%, 71.7% and 56.6%, respectively among migrants. Oral mucosal lesions (OML) were seen in 36.3% of participants. Among smokeless tobacco users, 44.6% had lesions. Adjusted odds ratio for OML was 4.5 (CI: 1.9 - 19.84) among smokeless tobacco users. CONCLUSIONS: The current use of smokeless tobacco and oral mucosal lesions are highly prevalent among migrant workers. PMID- 26855721 TI - Non Invasive XRF Analysis of Human Hair for Health State Determination of Breast Tissue. AB - BACKGROUND: Using hair samples to analyze the trace element concentrations is of interest among many researchers. X-ray fluorescence (XRF) and X-ray diffraction (XRD) are the most common methods in studying the structure and concentration of elements of tissues and also crystalline materials, using low energy X-ray. OBJECTIVES: In the present study, the detection ability of Wave Length X-ray Fluorescence (WLXRF) of breast cancer at early stages was evaluated and the results were compared with other routine modalities such as mammography. MATERIALS AND METHODS: Hair samples of 54 women (including 27 healthy and 27 patients) with average age of 52.03 +/- 11.44 years were analyzed. All the sample donors were Iranian women. For the measurements Wave Length X-ray Fluorescence (WLXRF) method was used. RESULTS: Trace elements in healthy individuals were higher than those in cancer patients. In addition, sensitivity of the used method (WLXRF) was 96% compared to mammography (77%) as a gold standard for breast cancer detection. CONCLUSIONS: Trace elements in healthy individuals were higher than cancer patients and it seems that WLXRF may be used as a safe, low cost and reliable method with sensitivity higher than those of the other two relevant methods, XRD and mammography. PMID- 26855723 TI - Characteristics of Patients With Transitional Cell Carcinoma of the Urinary Bladder in Kermanshah Province, Iran. AB - BACKGROUND: In Iran, bladder cancer is one of the most common malignancy sites among men, ranking as the fifth with age-specific incidence rate of about 11.2 per 100,000 males. It causes 8% of all malignancies in men and 3% of all malignancies in women. OBJECTIVES: The aim of this study was to report the epidemiological, clinical, and pathological features of bladder cancer in Western Iran compared to other studies. PATIENTS AND METHODS: This is a retrospective study between 2003 and 2014 when forty-four patients with bladder cancer referred to Hematology Clinic of Kermanshah, Kermanshah, Iran. Transitional cell carcinoma (TCC) was in 39 patients. RESULTS: In the patients with TCC, the mean age in diagnosis for them was 65.43 years (+/- 11.64), range of age 42 to 88 years , thirty-three patients (84.6%) were male, and six patients (15.4%) were female. Of 39 patients with TCC, 16 patients (41%) had metastasis. 21 patients (53.8%) were smoker and 16 patients (41%) had muscle invasive. 35 patients (89.7%) were histological high grade and the rest of patients were low grade. In the TCC patients with increasing age, metastasis and muscle invasive increased. CONCLUSIONS: The age presentation of TCC in West Iran was similar to other studies. Percentage of patients with high grade is more than other studies, and also the number of patients with bladder cancer has increased during last 4 years. For better results, studies must be conducted with more patients in this area, and other areas of Iran with checking of genetics, race and environmental factors. PMID- 26855722 TI - A Live Vector Expressing HPV16 L1 Generates an Adjuvant-Induced Antibody Response In-vivo. AB - BACKGROUND: The association between human papillomavirus (HPV) infections and cervical cancer has suggested the design of prophylactic and therapeutic vaccines against genital warts. The HPV capsid has made of two L1 and L2 coat proteins that have produced late in viral infections. Regarding to the recent studies, two commercial prophylactic vaccines have based on L1 viral like particles (VLPs) could strongly induce antibody responses, and protect human body from HPV infections. However, the use of these HPV vaccines has hindered due to their high cost and some limitations. Currently, among various vaccination strategies, live vector-based vaccines have attracted a great attention. OBJECTIVES: Herein, a non pathogenic strain of the protozoan organism known as Leishmania tarentolae has utilized to induce potent humoral immunity in mice model. MATERIALS AND METHODS: At first, cloning of HPV16 L1 gene into Leishmania expression vector has performed and confirmed by PCR and digestion with restriction enzymes. The promastigotes of Leishmania tarentolae (L.tar) have transfected with linearized DNA construct by electroporation. Protein expression has analyzed by SDS-PAGE and western blotting. Then, the immunogenicity of leishmania expressing L1 protein (L.tar-L1) has assessed in mice model. RESULTS: Our data has indicated that subcutaneous immunization of mice with the recombinant L.tar-L1 has led to enhance the levels of IgG1 and lgG2a in comparison with control groups. Furthermore, there was no significant increase in antibody levels between two and three times of immunizations. CONCLUSIONS: The recombinant live vector was able to induce humoral immunity in mice without need of any adjuvant. However, further studies have required to increase its efficiency. PMID- 26855724 TI - Oral Lymphoma Prevalence in Iranian Population: A Multicenter Retrospective Study. AB - BACKGROUND: Oral lymphoma is the second most common malignancy of the head and neck region after malignant epithelial tumors. OBJECTIVES: Considering the lack of a multicenter study on the frequency of oral lymphoma in Iran, this study aimed to assess the relative frequency of oral lymphomas in Iran during a 6-year period. MATERIALS AND METHODS: This multicenter, retrospective, cross-sectional study was conducted in two phases. In the first phase, cases of oral lymphoma registered in the cancer research center (CRC) of Shahid Beheshti university of medical sciences were extracted. The patient records and pathology reports of these patients were retrieved from the archives and age, sex and microscopic type site of the lesions were evaluated. RESULTS: Oral lymphoma accounts for 1% of head and neck malignancies and 8% of all lymphomas. From 2003 to 2008, a total of 437 new cases of oral lymphomas had been registered in the CRC. Diffuse large B cell lymphoma was found to be the most common form of oral lymphoma in the 6-year period with 240 (54.9%) registered cases. The majority of detected cases were in the 6th and 7th decades of life with a male to female ratio of 1:84. Tonsils were the most common site of occurrence of lymphoma in the oral cavity (77.8%). CONCLUSIONS: The age of onset, site of involvement, sex of patients, and histopathological subtype of oral lymphomas in the Iranian population were found to be similar to those of most other countries. PMID- 26855725 TI - Apoptosis/Necrosis Induction by Ultraviolet, in ER Positive and ER Negative Breast Cancer Cell Lines. AB - BACKGROUND: Ultraviolet (UV) light exposure has been one of the major inducers of apoptosis. UV exposure has caused pyrimidine dimers and DNA fragmentation which might lead to cell cycle arrest and apoptosis signals activation. UV induced apoptosis has investigated in MDA-MB 468 as an ER negative breast adenocarcinoma and MCF-7 as an ER positive breast cancer cell line. Apoptosis induction rate by UV might be different in these two types of cells due to different biological characteristics of the cell. OBJECTIVES: In this paper we have evaluated serial dose of UV-B exposure on ER positive and ER negative breast cancer cell lines and its effect on apoptosis or necrosis induction in these cells. MATERIALS AND METHODS: MDA-MB468 and MCF-7 cell lines have cultured for 24 hours and UV exposure has carried out at 290 nm at dose of 154 J/m(2) to 18 KJ/m(2) using UV lamp. UV exposed cells have incubated in cell culture condition for 24 or 48 hours following UV exposure and the cells have stained and analyzed by flow cytometry for apoptosis evaluation by Annexin V/PI method. RESULTS: Apoptosis rate (PI and Annexin V double positive cells) after 24 hours incubation was higher in 24 hours in comparison with 48 hours incubation in both cell lines. The frequency of PI positive MDA-MB 468 cells was higher than PI and Annexin V double positive cells after 48 hours. PI positive MDA-MB 468 cells were significantly higher than MCF-7 cells in 24 hours incubation time. CONCLUSIONS: The results have shown that MDA-MB 468 cells were more sensitive to UV exposure and DNA fragmentation and necrosis pathway was dominant in these cells. PMID- 26855727 TI - Health Manpower Development (HMD) Corner Stone of Improving National Health System. PMID- 26855726 TI - A Literature Survey on Cost-Effectiveness of Proton Beam Therapy in the Management of Breast Cancer Patients. AB - CONTEXT: Proton therapy has currently used to treat brain, spinal and prostate cancers, as well as Breast cancer. Proponents have cited the modality's ability to spare healthy tissue, but critics have claimed the benefit gained from its use has not validated its cost in comparison with photon therapy. The aim of this study was evaluation of proton therapy cost effectiveness versus photon therapy, in the Breast Cancer management through a literature survey. EVIDENCE ACQUISITION: Standard search strategies covering the querying of available online databases (MEDLINE(r), PubMed, EMBASE and Cochrane) have been applied. Database searches have conducted in an iterative manner during June-September 2015 to retrieve articles related to our policy. No specific key words have required as inclusion criteria; a relatively small number of studies exist on this topic, so a "bottom-up" search strategy has required. RESULTS: Three studies have modeled the costs and cost-effectiveness of PBT in breast cancer. The ICER has lied below the threshold for women at high risk of cardiac disease and so it could be judged cost-effective whereas it was above this threshold for other patients. The cost per QALY has gained would, however, be considerably lower if a population with high-risk of developing cardiac disease has treated. CONCLUSIONS: It has concluded that proton therapy for breast cancer could be cost-effective if appropriate risk groups have chosen as targets for the therapy. Also the number of patient whose radiation therapy has considered in their treatment schedule, was other important factor which could affect the decision on PBT cost effectiveness. PMID- 26855728 TI - The Economic Aspects of Medical Biotechnology. PMID- 26855729 TI - Differentiation of Definitive Endoderm from Human Induced Pluripotent Stem Cells on hMSCs Feeder in a Defined Medium. AB - BACKGROUND: The Definitive Endoderm (DE) differentiation using the undefined media and non-human feeders can cause contaminations in the generated cells for therapeutic applications. Therefore, generating safer and more appropriate DE cells is needed. This study compared five different methods to establish an appropriate method for inducing an efficient DE differentiation from Human Induced Pluripotent Stem Cells (hiPSCs) on an appropriate feeder in a more defined medium. METHODS: Human Induced Pluripotent Stem Cells (hiPSCs) were cultured on inactivated feeders. Passaged hiPSCs, without feeder, were incubated for three days with Activin-A and different endodermal differentiation media including 1-FBS, 2-B27, 3-ITS and albumin fraction-V, 4-B27 and ITS and 5-like the third medium. The feeder cells in the first four methods were Mouse Embryonic Fibroblasts (MEFs) and in the fifth method were human adult bone marrow Mesenchymal Stem Cells (hMSCs). DE markers FOXA2, SOX17 and CXCR4 and also pluripotency marker OCT4 were evaluated using qRT-PCR, as well as FOXA2 by the immunocytochemistry. RESULTS: QRT-PCR analysis showed that after three days, the expression levels of DE and pluripotency markers in the differentiated hiPSCs among all five groups did not have any significant differences. Similarly, the immunocytochemistry analysis demonstrated that the differentiated hiPSCs expressed FOXA2, with no significant differences. CONCLUSION: Despite this similarity in the results, the third differentiation medium has more defined and cost effective components. Furthermore, hMSC, a human feeder, is safer than MEF. Therefore, the fifth method is preferable among other DE differentiation methods and can serve as a fundamental method helping the development of regenerative medicine. PMID- 26855730 TI - The Effect of Angiotensin on the Quality of In Vitro Produced (IVP) Sheep Embryos and Expression of Na(+)/K(+)/ATPase. AB - BACKGROUND: The presence of rennin-angiotensin components in mammalian ovaries and their involvement in ovarian physiology have been established. In the present study, effects of angiotensin II (Ang II) on sodium-potassium adenosine triphosphatase (Na(+)/K(+)/ATPase) expression and development of sheep embryos was evaluated. METHODS: The abattoir-derived Cumulus Oocyte Complexes (COC) were randomly allocated into three experimental groups; group I) in vitro Maturation (IVM) of oocytes in the presence of Ang II followed by in vitro fertilization (IVF)/in vitro Culture (IVC) (IVM group), group II) IVM/IVF of oocytes followed by IVC wherein the embryos were exposed to Ang II on day 4 of IVC (D4 group), and group III) IVM/IVF and IVC of oocytes without any angiotensin (Control). The blastocyst and hatching rates were recorded on days 6 to 8. Day 8 embryos were immunostained with primary and secondary antibodies against Na(+)/K(+)/ATPase alpha1 and beta1 subunits. RESULTS: Addition of Ang II during IVM and IVC significantly increased the hatching rate of blastocysts on day 8 compared to the control. The trophectoderm and total blastocyst cells' numbers were significantly increased by addition of Ang II to the IVM and IVC media, though the expression of Na(+)/K(+)/ATPase alpha1 and beta1 subunits were positively influenced by the addition of Ang II on day 4 (D4 group). CONCLUSION: In conclusion, it seems Ang II through positive effects on embryos, expressed as the greater hatching rate and blastocyst cell number, could increase the sheep embryo developmental rate. These improvements might be partly related to the greater expression of Na(+)/K(+)/ATPase alpha1 and beta1 subunits when Ang II was added during IVC. PMID- 26855731 TI - Comparison of Three Escherichia coli Strains in Recombinant Production of Reteplase. AB - BACKGROUND: Escherichia coli (E. coli) is the most extensively used host for the production of recombinant proteins. However, most of the eukaryotic proteins are typically obtained as insoluble, misfolded inclusion bodies that need solubilization and refolding. Reteplase as a highly disulfide-bonded recombinant protein is an example of difficult to express protein in E. coli. METHODS: In this study, a codon optimized reteplase gene was synthetically prepared and cloned under the control of an IPTG inducible T7 promoter. The vector was simultaneously transformed and expressed in three different E. coli strains. The ability of strains for expression of this recombinant pharmaceutical was compared. Also, an attempt was made to increase the soluble production of reteplase in SHuffle T7 E. coli with alterations of expression condition like temperature, inducer concentration and oxygen supply. RESULTS: High amounts of reteplase were expressed as inclusion bodies in all three strains. BL21 (DE3) showed the highest level of expression in inclusion bodies followed by Rosetta gami (DE3) and Shuffle T7. Changes of expression conditions were insufficient for soluble expression of reteplase in SHuffle T7 as a genetically engineered host for production of disulfide bonded proteins. CONCLUSION: The oxidizing cytoplasm of Rosetta-gami and Shuffle T7 in addition to alterations of cultivation parameters could not result in soluble production of reteplase, although the inclusion bodies produced in these two strains might increase the rate of refolding procedure likely due to formation of folding intermediates. PMID- 26855732 TI - Cloning and Optimization of Soluble Vascular Endothelial Growth Factor165 Expression in Escherichia coli. AB - BACKGROUND: Vascular Endothelial Growth Factor (VEGF) is a coordinate regulator of physiological angiogenesis during embryogenesis, skeletal growth and reproductive functions. There are several types of VEGF, including VEGF165. VEGFs stimulate endothelial cell growth, angiogenesis, and capillary permeability. Low induction temperature is a major factor for expression of the recombinant VEGF165 in soluble form. The purpose of this study was cloning and optimization of soluble vascular endothelial growth factor165 expression in Escherichia coli (E. coli). METHODS: In this study, total RNA of HeLa cell [cervix epithelium] was extracted. The VEGF165 gene was amplified by reverse transcription polymerase chain reaction (RTPCR), and then VEGF165 was subcloned into prokaryotic expression vectors pET-32a(+) and transformed into BL21 (DE3) E. coli strain. VEGF165 expression was optimized by fine adjustments such as induction time and incubation temperature. VEGF165 was analyzed by DNA sequencing prior to expression and the protein was further characterized by SDS-PAGE and immunoblotting using His*tag specific polyclonal antibody. RESULTS: Our results demonstrated that VEGF165 was successfully cloned and expressed in pET-32a(+) vector. Optimization of the expression procedure showed that, induction by 1 mM IPTG at OD600=0.7 and overnight incubation at 22 degrees C resulted in the highest expression levels of soluble VEGF165. CONCLUSION: In this study, the expression of VEGF165 in a high soluble level was successfully cloned and optimized. PMID- 26855733 TI - Evaluation of the Anti-proliferative Effects of Ophiocoma erinaceus Methanol Extract Against Human Cervical Cancer Cells. AB - BACKGROUND: Marine organisms provide appreciable source of novel bioactive compounds with pharmacological potential. There is little information in correlation with anti-cancer activities of brittle star. In the present study, anti-neoplastic efficacy of Ophiocoma erinaceus methanol extract against human cervical cancer cells was investigated. METHODS: The HeLa cells were cultured and exposed to brittle star methanol extract for 24 and 48 hr. The anti-proliferative properties were examined by MTT assay and the type of cell death induced was evaluated through morphological changes, flow cytometry, Annexin kit and caspase assay. To assess the anti-metastatic activity, wound healing assay was conducted and photographs were taken from the scratched areas. Further, to understand molecular mechanism of cell apoptosis, the expression of Bax was evaluated. RESULTS: The morphological analysis and MTT assay exhibited that the brittle star methanol extract can exert dose dependent inhibitory effect on cells viability (IC50, 50 MUg/ml). Flow cytometry and fluorescence microscopy demonstrated increment of sub-G1 peak, early and late apoptosis in HeLa treated cells. Wound healing migration assay showed that brittle star extract has anti-neoplastic efficacy by inhibiting cell migration. Caspase assay and RT-PCR analysis revealed that brittle star methanol extract induced caspase dependent apoptosis in HeLa cells through up-regulation of caspase-3 followed by up-regulation of Bax gene which is a hallmark of intrinsic pathway recruitment. CONCLUSION: These results represented further insights into the chemopreventive potential of brittle star as a valuable source of unknown therapeutic agents against human cervical cancer. PMID- 26855734 TI - Computational Detection of piRNA in Human Using Support Vector Machine. AB - BACKGROUND: Piwi-interacting RNAs (piRNAs) are small non-coding RNAs (ncRNAs), with a length of about 24-32 nucleotides, which have been discovered recently. These ncRNAs play an important role in germline development, transposon silencing, epigenetic regulation, protecting the genome from invasive transposable elements, and the pathophysiology of diseases such as cancer. piRNA identification is challenging due to the lack of conserved piRNA sequences and structural elements. METHODS: To detect piRNAs, an appropriate feature set, including 8 diverse feature groups to encode each RNA was applied. In addition, a Support Vector Machine (SVM) classifier was used with optimized parameters for RNA classification. According to the obtained results, the classification performance using the optimized feature subsets was much higher than the one in previously published studies. RESULTS: Our results revealed 98% accuracy, Mathew' correlation coefficient of 98% and 99% specificity in discriminating piRNAs from the other RNAs. Also, the obtained results show that the proposed method outperforms its competitors. CONCLUSION: In this paper, a prediction method was proposed to identify piRNA in human. Also, 48 heterogeneous features (sequence and structural features) were used to encode RNAs. To assess the performance of the method, a benchmark dataset containing 515 piRNAs and 1206 types of other RNAs was constructed. Our method reached the accuracy of 99% on the benchmark dataset. Also, our analysis revealed that the structural features are the most contributing features in piRNA prediction. PMID- 26855735 TI - Outer Membrane Protein C (ompC) Gene as the Target for Diagnosis of Salmonella Species Isolated from Human and Animal Sources. AB - BACKGROUND: The use of selective and differential plating media is a simple method for the isolation of Salmonella spp. Recently, there has been a general move toward molecular methods of Salmonella detection and typing. METHODS: A total of 1200 different specimens collected from human and animal sources were involved in his study. 600 stool specimens from patients suffering from diarrhea and 600 specimens from gall bladder (bile) of cattle from Al-Diwaniya slaughter house, Iraq were used. Salmonella spp. were isolated and identified using bacterial culturing on selective media and colonies were tested by API 20Eand then serotyping through polyvalent antisera and conformation by Polymerase Chain Reaction (PCR). PCR was used to detect ompC gene encoding biosynthesis of outer membrane protein C of Salmonella genus. RESULTS: The results revealed that the rate of Salmonella isolates was 0.5% (3/600) from human and 1% (6/600) from animals. The PCR technique revealed that 9 isolates of Salmonella spp. harbored ompC gene. The results of this study revealed that the PCR technique had a high specificity in detection of Salmonella spp., in comparison to culture and biochemical test, Mini API 20 E and serological tests. The present study found no significant differences between human and animal isolates. CONCLUSION: Detection of ompC gene is a good method for detection of Salmonella species isolated from clinical specimens. It has a high specificity in comparison with other tests, with its advantages of greater speed and effectiveness than conventional detection methods. PMID- 26855737 TI - Epidemiologic and Drug Resistance Pattern of Vibrio cholerae O1 Biotype El Tor, Serotype Ogawa, in the 2011 Cholera Outbreak, in Alborz Province, Iran. AB - BACKGROUND: Although the national guidelines recommend special antibiotics, based on the antibiogram of National Reference Laboratory, it seems that, because of uncontrolled usage of antibiotics in the society and due to the changes in the serotypes causing the disease, it is essential to monitor the status of drug resistance, permanently, and to revise the current prescriptions guidelines. OBJECTIVES: This study aimed to assess the epidemiological aspects and drug resistance pattern of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, in cholera outbreak, in Alborz province in Iran, during 2011. MATERIALS AND METHODS: This is a cross-sectional study, which reviews a cholera epidemic that occurred in Iran. A total of 9844 specimens were taken from suspected cases, among diarrheal patients, via rectal swabs. The specimens were placed in Cary-Blair transport medium and sent to laboratory. Samples were enriched, in alkaline peptone water, and isolated on thiosulphate-citrate-bile salt-sucrose agar. From the 244 confirmed cases, 239 cases underwent antibiogram test, via disk diffusion method and based on national committee for clinical laboratory standards (NCCLS) instructions. The standard Escherichia coli ATCC 25922 was used for antibiogram quality control and, eventually, all results were interpreted and reported using NCCLS standard table. RESULTS: In total, until October 22, 2011, which was announced as the end of outbreak, 9844 samples were taken from diarrheal patients. Regarding the type of V. cholerae, 244 El Tor biotype positive cases were reported. The case fatality rate was 1.3%. The mean age of patients was 37.8 years and the highest incidence rate occurred in the age group 21 - 30 years. After conducting antibiotic susceptibility test in the 244 V. cholerae, biotype El Tor, serotype Ogawa, it was found that ciprofloxacin had the highest level of antibiotic susceptibility (99.6%) and the highest level of antibiotic resistance was observed in co-trimoxazole (95.4%). CONCLUSIONS: The results of our study show that the resistances to doxycycline and tetracycline, which are mentioned in multiple resources, as the most common antibiotic drugs for treating cholera, are increasing. PMID- 26855736 TI - A Study on Genetic Association of Interleukin-16 Single Nucleotide Polymorphism (rs1131445) With Chronic Hepatitis B Virus Infection in Iranian Patients. AB - BACKGROUND: Interleukin-16 (IL-16) is an immunomodulatory cytokine, which plays an important role in some inflammatory and autoimmune diseases such as hepatitis B, which is a major health concern worldwide. OBJECTIVES: In this study, we aimed to investigate the plausible association between IL-16 polymorphism and chronic HBV susceptibility in an Iranian population. PATIENTS AND METHODS: In a case control study, we analyzed rs1131445 polymorphism in the microRNA binding site of the IL-16 gene in 262 patients with chronic hepatitis B and 269 healthy controls, using the polymerase chain reaction-restriction fragment length polymorphism (PCR RFLP) method and DNA sequencing technology to confirm our results. RESULTS: Altogether, in this investigation, a significant association was observed between the IL-16 TC genotype compared with the TT genotype (OR = 0.696, 95% CI: 0.485 - 0.997, P = 0.048), after adjustments for confounders including age and gender. CONCLUSIONS: These findings show that immunogenetic factors, such as single nucleotide polymorphism in IL-16, could be a risk factor for susceptibility to chronic HBV infection. However, further investigations are needed to verify these results. PMID- 26855738 TI - Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Gene Polymorphisms and Hepatitis B Virus Infection. AB - BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an apoptotic molecule with a key role in the apoptosis of tumors and virus-infected cells. The association of 1525G/A and 1595C/T polymorphisms in the region of 3' UTR on the TRAIL gene has been shown in many cancers and diseases. Polymorphism at the positions of 1525G/A and 1595C/T might influence the clearance of hepatitis B virus (HBV). OBJECTIVES: This study was carried out to determine the role of the TRAIL gene polymorphisms in clinical outcome of HBV infection. PATIENTS AND METHODS: Polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) was applied to genotype TRAIL polymorphisms at positions 1525G/A and 1595C/T. To evaluate the TRAIL gene polymorphism in the 3' UTR region at position 1525G/A and 1595C/T, 147 patients with HBV infection were divided into three different groups of chronic hepatitis (n = 52), cirrhosis (n = 33), and carrier (n = 62) and there was a group of 101 healthy controls. RESULTS: Our data showed that genotypes 1525G/A and 1595C/T were in complete linkage disequilibrium and the genotype frequencies at the two positions were the same. No significant differences in frequencies of genotype and alleles at positions 1525G/A and 1595C/T were observed between all the three groups (P value > 0.05). CONCLUSIONS: According to our result, 1525G/A and 1595C/T were in strong linkage disequilibrium and the polymorphisms of the TRAIL gene in the 3' UTR region were not associated with the outcome of HBV infection. PMID- 26855739 TI - Antibiotic Resistance Pattern and Distribution of pslA Gene Among Biofilm Producing Pseudomonas aeruginosa Isolated From Waste Water of a Burn Center. AB - BACKGROUND: Pseudomonas aeruginosa is considered as a major cause of hospital acquired infections due to its high antibacterial resistance. Biofilm formation is a well-known pathogenic mechanism in P. aeruginosa infections, since sessile bacteria are protected in an extracellular matrix of exopolysaccharide. The expression of polysaccharide synthesis locus (pslA gene) can be important for biofilm formation by P. aeruginosa. OBJECTIVES: The purpose of this research was to evaluate the antibiotic resistance pattern and distribution of the pslA gene among biofilm-producing P. aeruginosa isolates obtained from waste water of Burn Centre in Guilan, Iran. MATERIALS AND METHODS: Fifty isolates of P. aeruginosa were obtained from waste water of a burn center. The P. aeruginosa isolates were identified using standard bacteriological procedures. Drug susceptibility test was performed by disk diffusion method for all the isolates against nine antimicrobial agents. Biofilm formation was measured by microtiter plate assay. Polymerase chain reaction (PCR) was used to identify the presence of the pslA gene among the isolates. RESULTS: Biofilm formation was observed in 70% of the P. aeruginosa isolates. The potential formation of biofilm was significantly associated with resistance to gentamicin, imipenem, tobramycin and piperacillin. In addition, the pslA gene only existed in biofilm-producing isolates with a frequency of 42.9% (n = 15). CONCLUSIONS: The findings of the present study well demonstrated that the P. aeruginosa biofilm-producing isolates were more resistant to the tested antibiotics. Furthermore, because of wide distribution, it seems that the pslA gene is associated with biofilm formation. PMID- 26855740 TI - Phylogenetic and Transcripts Profiling of Glucose Sensing Related Genes in Candida glabrata. AB - BACKGROUND: The sensing mechanism of glucose in Saccharomyces cerevisiae is well studied. However, such information is scarcely found in other yeast species such as Candida glabrata. OBJECTIVES: This study aimed to identify the glucose sensing pathway related genes of C. glabrata and to analyze the regulation pattern of these genes in response to different surrounding glucose concentrations through the quantitative real time polymerase chain reaction (qRT-PCR). MATERIALS AND METHODS: Phylogenetic analysis was carried out on predicted amino acid sequences of C. glabrata and S. cerevisiae to compare their degree of similarity. In addition, the growth of C. glabrata in response to different amounts of glucose (0%, 0.01%, 0.1%, 1% and 2%) was evaluated via the spot dilution assay on prepared agar medium. Besides, the SNF3 and RGT2, which act as putative glucose sensors, and the RGT1 and MIG1, which act as putative transcriptional regulators and selected downstream hexose transporters (HXTs), were analysed through qRT-PCR analysis for the gene expression level under different glucose concentrations. RESULTS: Comparative analysis of predicted amino acids in the phylogenetic tree showed high similarity between C. glabrata and S cerevisiae. Besides, C. glabrata demonstrated the capability to grow in glucose levels as low as 0.01% in the spot dilution assay. In qRT-PCR analysis, differential expressions were observed in selected genes when C. glabrata was subjected to different glucose concentrations. CONCLUSIONS: The constructed phylogenetic tree suggests the close evolutionary relationship between C. glabrata and S. cerevisiae. The capability of C. glabrata to grow in extremely low glucose environments and the differential expression of selected glucose-sensing related genes suggested the possible role of these genes in modulating the growth of C. glabrata in response to different glucose concentrations. This study helps deepen our understanding of the glucose sensing mechanism in C. glabrata and serves to provide fundamental data that may assist in unveiling this mechanism as a potential drug target. PMID- 26855741 TI - Identification and Sequencing of Candida krusei Aconitate Hydratase Gene Using Rapid Amplification of cDNA Ends Method and Phylogenetic Analysis. AB - BACKGROUND: The production and development of an effective fungicidal drug requires the identification of an essential fungal protein as a drug target. Aconitase (ACO) is a mitochondrial protein that plays a vital role in tricarboxylic acid (TCA) cycle and thus production of energy within the cell. OBJECTIVES: The current study aimed to sequence Candida krusei ACO gene and determine any amino acid residue differences between human and fungal aconitases to obtain selective inhibition. MATERIALS AND METHODS: Candida krusei (ATCC: 6258) aconitase gene was determined by 5'Rapid Amplification of cDNA Ends (RACE) method and degenerate Polymerase Chain Reaction (PCR) and analyzed using bioinformatics softwares. RESULTS: One thousand-four hundred-nineteen nucleotide of C. krusei aconitase gene were clarified and submitted in Genbank as a partial sequence and then taxonomic location of C. krusei was determined by nucleotide and amino acid sequences of this gene. The comparison of nucleotide and amino acid sequences of Candida species ACO genes showed that C. krusei possessed characteristic sequences. No significant differences were observed between C. krusei and human aconitases within the active site amino acid residues. CONCLUSIONS: Results of the current study indicated that aconitase was not a suitable target to design new anti-fungal drugs that selectively block this enzyme. PMID- 26855742 TI - Comparative Proteomics Analysis of Two Strains of Neisseria meningitidis Serogroup B and Neisseria lactamica. AB - BACKGROUND: Antigenic similarities between Neisseria lactamica as a commensal species and N. meningitidis serogroup B (NmB) as an important cause of meningitis infection have been considered for the development of an effective vaccine based on their common proteins to prevent life-threatening bacterial meningitis. OBJECTIVES: The main aims of this study were to determine whole proteome profiles of N. lactamica strains and to compare them with whole proteome profile of a reference strain of NmB for identification of some of common proteins between the two species. MATERIALS AND METHODS: We compared the whole proteomic profiles of N. lactamica strains and a reference strain of NmB. Lysates from bacterial strains were resolved by two-dimensional gel electrophoresis (2-DE), followed by Coomassie Brilliant blue staining. Some of the protein spots were excised from the gel and subjected to matrix-assisted laser desorption/ionization-tandem time of-flight mass spectrometry (MALDI-TOF/TOF MS) analysis. RESULTS: The analysis of Coomassie-stained gels using ImageMaster 2D Platinum software identified approximately 800 reproducible protein spots in the range of pI 4.5 - 9.5 and M r of 8 - 100 kDa for each 2-DE gel of the studied bacterial strains. By comparing proteome maps of 2-DE gels, more than 200 common protein spots were recognized between the two species. Forty-eight common protein spots between the studied bacterial strains were identified by MALDI-TOF/TOF-MS. The results indicated that among the protein spots identified by MOLDI-TOF/TOF mass spectrometry, the groups of proteins included cell surface, energy metabolism, amino acid transport and metabolism, coenzyme metabolism, defense, multifunctional cellular processes, DNA, RNA and protein synthesis, ribosomal structure, regulatory functions, replication, transcription, translation, unknown and hypothetical proteins with unknown function. We found that N. lactamica strains have a proteome profile somewhat similar to each other and slightly different with NmB. CONCLUSIONS: These results show the usefulness of proteome analysis in successful identification of the common proteins between N. lactamica strains and NmB. This proteomics analysis is the starting point in the path of knowledge development about whole proteome profiles of N. lactamica strains. PMID- 26855743 TI - Morphological and Bactericidal Effects of Amikacin, Meropenem and Imipenem on Pseudomonas aeruginosa. AB - BACKGROUND: Pseudomonas aeruginosa might be converted to coccoid bacteria under antibiotic stress. Bacterial conversion would increase resistance to antibiotics due to changes in cell wall crosslink or decreased metabolic activity. Morphology of P. aeruginosa under stress conditions (presence of antibiotics) can be changed to elongated bacilli, U shape and finally coccoid bacteria. Results of several researches showed that coccoid bacteria are one of the most important aspects of drug resistance. It would be the major reason for treatment failure. OBJECTIVES: The aim of this study was to determine in vitro morphological and bactericidal effects of amikacin, meropenem and imipenem on P. aeruginosa isolated from clinical specimens. MATERIALS AND METHODS: Eight P. aeruginosa isolates obtained from clinical samples of burned patients and standard strain ATCC 27853 were used in this study. Isolates were identified by biochemical tests and confirmed by PCR method using ITS specific primer. Minimum inhibitory concentrations (MICs) of three antibiotics were determined by E-test method. Bacteria were exposed to antibiotics at different concentrations. Bacterial morphology in different days was examined by specific microscope and viability of isolates was examined by flow cytometry. RESULTS: All used antibiotics at sub MIC concentration had capability to induce coccoid bacteria. The highest rate of induced coccoid bacteria was 98.2% after 8 days, with contribution of imipenem and meropenem at 2 MUg/mL concentration. Amikacin at 4 MUg/mL concentration induced lower rate of coccoid bacteria (55.05%). Amikacin had a strong bactericidal effect on coccoid bacteria at 8 MUg/mL concentration. Imipenem and meropenem showed very weak bactericidal effect on coccoid bacteria. CONCLUSIONS: Induction of coccoid form of P. aeruginosa may be one of the important reasons for antibiotic treatment failure; therefore, prescribed dose of antibiotics should be carefully managed to prevent increasing antibiotic resistance and coccoid bacteria induction. PMID- 26855744 TI - Heterologous Expression of Hepatitis C Virus Core Protein in Oil Seeds of Brassica napus L. AB - BACKGROUND: Hepatitis c virus (HCV), prevalent among 3% of the world population, is a major worldwide public health concern and an effective vaccination could help to overcome this problem. Plant seeds as low-cost vaccine expression platforms are highly desirable to produce antigens. OBJECTIVES: The present study was aimed at investigating the possible expression of recombinant HCV core protein, as a leading HCV vaccine candidate, in canola (Brassica napus) plant seeds in order to be used as an effective immunogen for vaccine researches. MATERIALS AND METHODS: A codon-optimized gene harboring the Kozak sequence, 6 * His-tag, HCVcp (1 - 122 residues) and KDEL (Lys-Asp-Glu-Leu) peptide in tandem was designed and expressed under the control of the seed specific promoter, fatty acid elongase 1 (FAE1), to accumulate the recombinant protein in canola (B. napus L.) seeds. Transgenic lines were screened and the presence of the transgene was confirmed in the T0 plants by polymerase chain reaction (PCR). The quantity and quality of the HCV core protein (HCVcp) in transgenic seeds were evaluated by enzyme-linked immunosorbent assay (ELISA) and western blot, respectively. RESULTS: Western blot analysis using anti-His antibody confirmed the presence of a 15 kDa protein in the seeds of T1 transgenic lines. The amount of antigenic protein accumulated in the seeds of these transgenic lines was up to 0.05% of the total soluble protein (TSP). CONCLUSIONS: The canola oilseeds could provide a useful expression system to produce HCV core protein as a vaccine candidate. PMID- 26855745 TI - Detection of Parvovirus B19 Infection in Thalasemic Patients in Isfahan Province, Iran. AB - BACKGROUND: Parvovirus B19, a member of the Erythrovirus genus of Parvoviridae family, causes various clinical illnesses including infectious erythema, arthropathy, hydrops fetalis or congenital anemia, and transient aplastic crises. The B19 virus can be transmitted through respiratory secretions, blood products, and blood transfusion. OBJECTIVES: The aim of this study was to detect the B19 virus in thalassemia patients in Isfahan, Iran. PATIENTS AND METHODS: The prevalence of parvovirus B19 infection was compared between thalassemia major patients and healthy subjects. Plasma samples were collected from 30 thalassemia patients from Isfahan, Iran. Thirty patients without any blood complications were considered as the control group. After DNA extraction from the plasma samples, polymerase chain reaction was performed for parvovirus B19 detection. RESULTS: The parvovirus B19-specific nucleotide sequence was detected in 6 patients (20%). None of the samples obtained from the 30 control subjects tested positive for B19. CONCLUSIONS: In this study B19-Parvovirus infection were detected in patients with hematologic disorders in comparison with control subjects. Screening of patients with a high risk of parvovirus B19 infection can considerably reduce the incidence and prevalence of B19 infection. PMID- 26855746 TI - Collagen V-heterozygous and -null supraspinatus tendons exhibit altered dynamic mechanical behaviour at multiple hierarchical scales. AB - Tendons function using a unique set of mechanical properties governed by the extracellular matrix and its ability to respond to varied multi-axial loads. Reduction of collagen V expression, such as in classic Ehlers-Danlos syndrome, results in altered fibril morphology and altered macroscale mechanical function in both clinical and animal studies, yet the mechanism by which changes at the fibril level lead to macroscale functional changes has not yet been investigated. This study addresses this by defining the multiscale mechanical response of wild type, collagen V-heterozygous and -null supraspinatus tendons. Tendons were subjected to mechanical testing and analysed for macroscale properties, as well as microscale (fibre re-alignment) and nanoscale (fibril deformation and sliding) responses. In many macroscale parameters, results showed a dose-dependent response with severely decreased properties in the null group. In addition, both heterozygous and null groups responded to load faster than in wild-type tendons via earlier fibre re-alignment and fibril stretch. However, the heterozygous group exhibited increased fibril sliding, while the null group exhibited no fibril sliding. These studies demonstrate that dynamic responses play an important role in determining overall function and that collagen V is a critical regulator in the development of these relationships. PMID- 26855748 TI - Force fields for simulating the interaction of surfaces with biological molecules. AB - The interaction of biomolecules with solid interfaces is of fundamental importance to several emerging biotechnologies such as medical implants, anti fouling coatings and novel diagnostic devices. Many of these technologies rely on the binding of peptides to a solid surface, but a full understanding of the mechanism of binding, as well as the effect on the conformation of adsorbed peptides, is beyond the resolution of current experimental techniques. Nanoscale simulations using molecular mechanics offer potential insights into these processes. However, most models at this scale have been developed for aqueous peptide and protein simulation, and there are no proven models for describing biointerfaces. In this review, we detail the current research towards developing a non-polarizable molecular model for peptide-surface interactions, with a particular focus on fitting the model parameters as well as validation by choice of appropriate experimental data. PMID- 26855747 TI - Modelling approaches for evaluating multiscale tendon mechanics. AB - Tendon exhibits anisotropic, inhomogeneous and viscoelastic mechanical properties that are determined by its complicated hierarchical structure and varying amounts/organization of different tissue constituents. Although extensive research has been conducted to use modelling approaches to interpret tendon structure-function relationships in combination with experimental data, many issues remain unclear (i.e. the role of minor components such as decorin, aggrecan and elastin), and the integration of mechanical analysis across different length scales has not been well applied to explore stress or strain transfer from macro- to microscale. This review outlines mathematical and computational models that have been used to understand tendon mechanics at different scales of the hierarchical organization. Model representations at the molecular, fibril and tissue levels are discussed, including formulations that follow phenomenological and microstructural approaches (which include evaluations of crimp, helical structure and the interaction between collagen fibrils and proteoglycans). Multiscale modelling approaches incorporating tendon features are suggested to be an advantageous methodology to understand further the physiological mechanical response of tendon and corresponding adaptation of properties owing to unique in vivo loading environments. PMID- 26855750 TI - Slip knots and unfastening topologies enhance toughness without reducing strength of silk fibroin fibres. AB - The combination of high strength and high toughness is a desirable feature that structural materials should display. However, while in the past, engineers had to compromise on either strength or toughness depending on the requested application, nowadays, new toughening strategies are available to provide strong materials with high toughness. In this paper, we focus on one of such strategy, which requires no chemical treatment, but the implementation of slip knots with optimized shape and size in the involved material, which is silkworm silk in this case. In particular, a variety of slip knot topologies with different unfastening mechanisms are investigated, including even complex knots usually used in the textile industry, and their efficiency in enhancing toughness of silk fibres is discussed. PMID- 26855751 TI - Continuum theory of fibrous tissue damage mechanics using bond kinetics: application to cartilage tissue engineering. AB - This study presents a damage mechanics framework that employs observable state variables to describe damage in isotropic or anisotropic fibrous tissues. In this mixture theory framework, damage is tracked by the mass fraction of bonds that have broken. Anisotropic damage is subsumed in the assumption that multiple bond species may coexist in a material, each having its own damage behaviour. This approach recovers the classical damage mechanics formulation for isotropic materials, but does not appeal to a tensorial damage measure for anisotropic materials. In contrast with the classical approach, the use of observable state variables for damage allows direct comparison of model predictions to experimental damage measures, such as biochemical assays or Raman spectroscopy. Investigations of damage in discrete fibre distributions demonstrate that the resilience to damage increases with the number of fibre bundles; idealizing fibrous tissues using continuous fibre distribution models precludes the modelling of damage. This damage framework was used to test and validate the hypothesis that growth of cartilage constructs can lead to damage of the synthesized collagen matrix due to excessive swelling caused by synthesized glycosaminoglycans. Therefore, alternative strategies must be implemented in tissue engineering studies to prevent collagen damage during the growth process. PMID- 26855749 TI - Modelling of bone fracture and strength at different length scales: a review. AB - In this paper, we review analytical and computational models of bone fracture and strength. Bone fracture is a complex phenomenon due to the composite, inhomogeneous and hierarchical structure of bone. First, we briefly summarize the hierarchical structure of bone, spanning from the nanoscale, sub-microscale, microscale, mesoscale to the macroscale, and discuss experimental observations on failure mechanisms in bone at these scales. Then, we highlight representative analytical and computational models of bone fracture and strength at different length scales and discuss the main findings in the context of experiments. We conclude by summarizing the challenges in modelling of bone fracture and strength and list open topics for scientific exploration. Modelling of bone, accounting for different scales, provides new and needed insights into the fracture and strength of bone, which, in turn, can lead to improved diagnostic tools and treatments of bone diseases such as osteoporosis. PMID- 26855752 TI - Patient-specific blood rheology in sickle-cell anaemia. AB - Sickle-cell anaemia (SCA) is an inherited blood disorder exhibiting heterogeneous cell morphology and abnormal rheology, especially under hypoxic conditions. By using a multiscale red blood cell (RBC) model with parameters derived from patient-specific data, we present a mesoscopic computational study of the haemodynamic and rheological characteristics of blood from SCA patients with hydroxyurea (HU) treatment (on-HU) and those without HU treatment (off-HU). We determine the shear viscosity of blood in health as well as in different states of disease. Our results suggest that treatment with HU improves or worsens the rheological characteristics of blood in SCA depending on the degree of hypoxia. However, on-HU groups always have higher levels of haematocrit-to-viscosity ratio (HVR) than off-HU groups, indicating that HU can indeed improve the oxygen transport potential of blood. Our patient-specific computational simulations suggest that the HVR level, rather than the shear viscosity of sickle RBC suspensions, may be a more reliable indicator in assessing the response to HU treatment. PMID- 26855753 TI - A chemo-mechanical free-energy-based approach to model durotaxis and extracellular stiffness-dependent contraction and polarization of cells. AB - We propose a chemo-mechanical model based on stress-dependent recruitment of myosin motors to describe how the contractility, polarization and strain in cells vary with the stiffness of their surroundings and their shape. A contractility tensor, which depends on the distribution of myosin motors, is introduced to describe the chemical free energy of the cell due to myosin recruitment. We explicitly include the contributions to the free energy that arise from mechanosensitive signalling pathways (such as the SFX, Rho-Rock and MLCK pathways) through chemo-mechanical coupling parameters. Taking the variations of the total free energy, which consists of the chemical and mechanical components, in accordance with the second law of thermodynamics provides equations for the temporal evolution of the active stress and the contractility tensor. Following this approach, we are able to recover the well-known Hill relation for active stresses, based on the fundamental principles of irreversible thermodynamics rather than phenomenology. We have numerically implemented our free energy-based approach to model spatial distribution of strain and contractility in (i) cells supported by flexible microposts, (ii) cells on two-dimensional substrates, and (iii) cells in three-dimensional matrices. We demonstrate how the polarization of the cells and the orientation of stress fibres can be deduced from the eigenvalues and eigenvectors of the contractility tensor. Our calculations suggest that the chemical free energy of the cell decreases with the stiffness of the extracellular environment as the cytoskeleton polarizes in response to stress dependent recruitment of molecular motors. The mechanical energy, which includes the strain energy and motor potential energy, however, increases with stiffness, but the overall energy is lower for cells in stiffer environments. This provides a thermodynamic basis for durotaxis, whereby cells preferentially migrate towards stiffer regions of the extracellular environment. Our models also explain, from an energetic perspective, why the shape of the cells can change in response to stiffness of the surroundings. The effect of the stiffness of the nucleus on its shape and the orientation of the stress fibres is also studied for all the above geometries. Along with making testable predictions, we have estimated the magnitudes of the chemo-mechanical coupling parameters for myofibroblasts based on data reported in the literature. PMID- 26855754 TI - Cell-matrix interaction during strain-dependent remodelling of simulated collagen networks. AB - The importance of tissue remodelling is widely accepted, but the mechanism by which the remodelling process occurs remains poorly understood. At the tissue scale, the concept of tensional homeostasis, in which there exists a target stress for a cell and remodelling functions to move the cell stress towards that target, is an important foundation for much theoretical work. We present here a theoretical model of a cell in parallel with a network to study what factors of the remodelling process help the cell move towards mechanical stability. The cell network system was deformed and kept at constant stress. Remodelling was modelled by simulating strain-dependent degradation of collagen fibres and four different cases of collagen addition. The model did not lead to complete tensional homeostasis in the range of conditions studied, but it showed how different expressions for deposition and removal of collagen in a fibre network can interact to modulate the cell's ability to shield itself from an imposed stress by remodelling the surroundings. This study also showed how delicate the balance between deposition and removal rates is and how sensitive the remodelling process is to small changes in the remodelling rules. PMID- 26855755 TI - Tunability of collagen matrix mechanical properties via multiple modes of mineralization. AB - Functionally graded, mineralized collagen tissues exist at soft-to-hard material attachments throughout the body. However, the details of how collagen and hydroxyapatite mineral (HA) interact are not fully understood, hampering efforts to develop tissue-engineered constructs that can assist with repair of injuries at the attachments of soft tissues to bone. In this study, spatial control of mineralization was achieved in collagen matrices using simulated body fluids (SBFs). Based upon previous observations of poor bonding between reconstituted collagen and HA deposited using SBF, we hypothesized that mineralizing collagen in the presence of fetuin (which inhibits surface mineralization) would lead to more mineral deposition within the scaffold and therefore a greater increase in stiffness and toughness compared with collagen mineralized without fetuin. We tested this hypothesis through integrated synthesis, mechanical testing and modelling of graded, mineralized reconstituted collagen constructs. Results supported the hypothesis, and further suggested that mineralization on the interior of reconstituted collagen constructs, as promoted by fetuin, led to superior bonding between HA and collagen. The results provide us guidance for the development of mineralized collagen scaffolds, with implications for bone and tendon-to-bone tissue engineering. PMID- 26855757 TI - Tension tests on mammalian collagen fibrils. AB - A brief overview of isolated collagen fibril mechanics testing is followed by presentation of the first results testing fibrils isolated from load-bearing mammalian tendons using a microelectromechanical systems platform. The in vitro modulus (326 +/- 112 MPa) and fracture stress (71 +/- 23 MPa) are shown to be lower than previously measured on fibrils extracted from sea cucumber dermis and tested with the same technique. Scanning electron microscope images show the fibrils can fail with a mechanism that involves circumferential rupture, whereas the core of the fibril stays at least partially intact. PMID- 26855756 TI - Experimental studies of bone mechanoadaptation: bridging in vitro and in vivo studies with multiscale systems. AB - Despite advancements in technology and science over the last century, the mechanisms underlying Wolff's law-bone structure adaptation in response to physical stimuli-remain poorly understood, limiting the ability to effectively treat and prevent skeletal diseases. A challenge to overcome in the study of the underlying mechanisms of this principle is the multiscale nature of mechanoadaptation. While there exist in silico systems that are capable of studying across these scales, experimental studies are typically limited to interpretation at a single dimension or time point. For instance, studies of single-cell responses to defined physical stimuli offer only a limited prediction of the whole bone response, while overlapping pathways or compensatory mechanisms complicate the ability to isolate critical targets in a whole animal model. Thus, there exists a need to develop experimental systems capable of bridging traditional experimental approaches and informing existing multiscale theoretical models. The purpose of this article is to review the process of mechanoadaptation and inherent challenges in studying its underlying mechanisms, discuss the limitations of traditional experimental systems in capturing the many facets of this process and highlight three multiscale experimental systems which bridge traditional approaches and cover relatively understudied time and length scales in bone adaptation. PMID- 26855758 TI - Advancing multiscale structural mapping of the brain through fluorescence imaging and analysis across length scales. AB - Brain function emerges from hierarchical neuronal structure that spans orders of magnitude in length scale, from the nanometre-scale organization of synaptic proteins to the macroscopic wiring of neuronal circuits. Because the synaptic electrochemical signal transmission that drives brain function ultimately relies on the organization of neuronal circuits, understanding brain function requires an understanding of the principles that determine hierarchical neuronal structure in living or intact organisms. Recent advances in fluorescence imaging now enable quantitative characterization of neuronal structure across length scales, ranging from single-molecule localization using super-resolution imaging to whole-brain imaging using light-sheet microscopy on cleared samples. These tools, together with correlative electron microscopy and magnetic resonance imaging at the nanoscopic and macroscopic scales, respectively, now facilitate our ability to probe brain structure across its full range of length scales with cellular and molecular specificity. As these imaging datasets become increasingly accessible to researchers, novel statistical and computational frameworks will play an increasing role in efforts to relate hierarchical brain structure to its function. In this perspective, we discuss several prominent experimental advances that are ushering in a new era of quantitative fluorescence-based imaging in neuroscience along with novel computational and statistical strategies that are helping to distil our understanding of complex brain structure. PMID- 26855759 TI - Cell and nanoparticle transport in tumour microvasculature: the role of size, shape and surface functionality of nanoparticles. AB - Through nanomedicine, game-changing methods are emerging to deliver drug molecules directly to diseased areas. One of the most promising of these is the targeted delivery of drugs and imaging agents via drug carrier-based platforms. Such drug delivery systems can now be synthesized from a wide range of different materials, made in a number of different shapes, and coated with an array of different organic molecules, including ligands. If optimized, these systems can enhance the efficacy and specificity of delivery compared with those of non targeted systems. Emerging integrated multiscale experiments, models and simulations have opened the door for endless medical applications. Current bottlenecks in design of the drug-carrying particles are the lack of knowledge about the dispersion of these particles in the microvasculature and of their subsequent internalization by diseased cells (Bao et al. 2014 J. R. Soc. Interface 11, 20140301 (doi:10.1098/rsif.2014.0301)). We describe multiscale modelling techniques that study how drug carriers disperse within the microvasculature. The immersed molecular finite-element method is adopted to simulate whole blood including blood plasma, red blood cells and nanoparticles. With a novel dissipative particle dynamics method, the beginning stages of receptor-driven endocytosis of nanoparticles can be understood in detail. Using this multiscale modelling method, we elucidate how the size, shape and surface functionality of nanoparticles will affect their dispersion in the microvasculature and subsequent internalization by targeted cells. PMID- 26855760 TI - Collagen network strengthening following cyclic tensile loading. AB - The bulk mechanical properties of tissues are highly tuned to the physiological loads they experience and reflect the hierarchical structure and mechanical properties of their constituent parts. A thorough understanding of the processes involved in tissue adaptation is required to develop multi-scale computational models of tissue remodelling. While extracellular matrix (ECM) remodelling is partly due to the changing cellular metabolic activity, there may also be mechanically directed changes in ECM nano/microscale organization which lead to mechanical tuning. The thermal and enzymatic stability of collagen, which is the principal load-bearing biopolymer in vertebrates, have been shown to be enhanced by force suggesting that collagen has an active role in ECM mechanical properties. Here, we ask how changes in the mechanical properties of a collagen based material are reflected by alterations in the micro/nanoscale collagen network following cyclic loading. Surprisingly, we observed significantly higher tensile stiffness and ultimate tensile strength, roughly analogous to the effect of work hardening, in the absence of network realignment and alterations to the fibril area fraction. The data suggest that mechanical loading induces stabilizing changes internal to the fibrils themselves or in the fibril-fibril interactions. If such a cell-independent strengthening effect is operational in vivo, then it would be an important consideration in any multiscale computational approach to ECM growth and remodelling. PMID- 26855761 TI - A novel fibre-ensemble level constitutive model for exogenous cross-linked collagenous tissues. AB - Exogenous cross-linking of soft collagenous tissues is a common method for biomaterial development and medical therapies. To enable improved applications through computational methods, physically realistic constitutive models are required. Yet, despite decades of research, development and clinical use, no such model exists. In this study, we develop the first rigorous full structural model (i.e. explicitly incorporating various features of the collagen fibre architecture) for exogenously cross-linked soft tissues. This was made possible, in-part, with the use of native to cross-linked matched experimental datasets and an extension to the collagenous structural constitutive model so that the uncross linked collagen fibre responses could be mapped to the cross-linked configuration. This allowed us to separate the effects of cross-linking from kinematic changes induced in the cross-linking process, which in turn allowed the non-fibrous tissue matrix component and the interaction effects to be identified. It was determined that the matrix could be modelled as an isotropic material using a modified Yeoh model. The most novel findings of this study were that: (i) the effective collagen fibre modulus was unaffected by cross-linking and (ii) fibre-ensemble interactions played a large role in stress development, often dominating the total tissue response (depending on the stress component and loading path considered). An important utility of the present model is its ability to separate the effects of exogenous cross-linking on the fibres from changes due to the matrix. Applications of this approach include the utilization in the design of novel chemical treatments to produce specific mechanical responses and the study of fatigue damage in bioprosthetic heart valve biomaterials. PMID- 26855762 TI - Real-time, whole-brain, temporally resolved pressure responses in translational head impact. AB - Theoretical debate still exists on the role of linear acceleration ( a lin) on the risk of brain injury. Recent injury metrics only consider head rotational acceleration ( a rot) but not a lin, despite that real-world on-field head impacts suggesting a lin significantly improves a concussion risk function. These controversial findings suggest a practical challenge in integrating theory and real-world experiment. Focusing on tissue-level mechanical responses estimated from finite-element (FE) models of the human head, rather than impact kinematics alone, may help address this debate. However, the substantial computational cost incurred (runtime and hardware) poses a significant barrier for their practical use. In this study, we established a real-time technique to estimate whole-brain a lin-induced pressures. Three hydrostatic atlas pressures corresponding to translational impacts (referred to as 'brain print') along the three major axes were pre-computed. For an arbitrary a lin profile at any instance in time, the atlas pressures were linearly scaled and then superimposed to estimate whole brain responses. Using 12 publically available, independently measured or reconstructed real-world a lin profiles representative of a range of impact/injury scenarios, the technique was successfully validated (except for one case with an extremely short impulse of approx. 1 ms). The computational cost to estimate whole-brain pressure responses for an entire a lin profile was less than 0.1 s on a laptop versus typically hours on a high-end multicore computer. These findings suggest the potential of the simple, yet effective technique to enable future studies to focus on tissue-level brain responses, rather than solely relying on global head impact kinematics that have plagued early and contemporary brain injury research to date. PMID- 26855764 TI - Correction to 'Magnetic targeting of microbubbles against physiologically relevant flow conditions'. AB - [This corrects the article DOI: 10.1098/rsfs.2015.0001.]. PMID- 26855763 TI - Tissue constructs: platforms for basic research and drug discovery. AB - The functions, form and mechanical properties of cells are inextricably linked to their extracellular environment. Cells from solid tissues change fundamentally when, isolated from this environment, they are cultured on rigid two-dimensional substrata. These changes limit the significance of mechanical measurements on cells in two-dimensional culture and motivate the development of constructs with cells embedded in three-dimensional matrices that mimic the natural tissue. While measurements of cell mechanics are difficult in natural tissues, they have proven effective in engineered tissue constructs, especially constructs that emphasize specific cell types and their functions, e.g. engineered heart tissues. Tissue constructs developed as models of disease also have been useful as platforms for drug discovery. Underlying the use of tissue constructs as platforms for basic research and drug discovery is integration of multiscale biomaterials measurement and computational modelling to dissect the distinguishable mechanical responses separately of cells and extracellular matrix from measurements on tissue constructs and to quantify the effects of drug treatment on these responses. These methods and their application are the main subjects of this review. PMID- 26855766 TI - A novel class of copper(II)- and zinc(II)-bound non-steroidal anti-inflammatory drugs that inhibits acute inflammation in vivo. AB - BACKGROUND: The ability of Zn(II) and Cu(II) metal complexes of non-steroidal anti-inflammatory drugs (NSAIDs) to inhibit acute arterial inflammation in vivo has been studied. RESULTS: When acute vascular inflammation was induced in normocholesterolemic New Zealand White rabbits by inserting a non-occlusive silastic collar around the common carotid artery, a single oral dose of Cu(II) indomethacin (Cu(II)Indo, 3 mg/kg) administered by laparotomy achieved a 67 % (8.2 +/- 1.7 vs. 2.7 +/- 0.4 image units, p < 0.05) reduction in endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) but did not inhibit endothelial intercellular adhesion molecule (ICAM-1) expression significantly. Treatment with Cu(II)-acemetacin (Cu(II)ACM, 3 mg/kg) led to a profound 88 % (8.2 +/- 1.7 vs. 1.0 +/- 0.5 image units, p < 0.01) reduction in endothelial VCAM-1 expression but did not inhibit ICAM-1 expression, while treatment with Zn(II) acemetacin (Zn(II)ACM, 3 mg/kg) led to an 84 % (19.3 +/- 1.0 vs. 3.1 +/- 1.2 image units, p < 0.01) reduction in endothelial ICAM-1 expression and did not inhibit VCAM-1 expression. No adverse gastric, hepatic or renal effects were observed in treated animals. CONCLUSION: These findings provide the "proof of concept" that this novel class of drug, where there is complexation of NSAIDs with metal ions, has substantial anti-inflammatory effects in an animal model of acute vascular inflammation with the possibility of low rates of adverse effects. PMID- 26855767 TI - How can we improve amniocentesis decision-making? AB - The decision to have an amniocentesis entails a trade-off between a risk of procedure associated miscarriage and the benefit of obtaining diagnostic information to identify Down syndrome or other chromosomal aneuploidy. Ideally, this trade-off is informed by first and second trimester pre-natal screening tests, such that women with low risk screening test results are not encouraged to have an amniocentesis. In a recent IJHPR article, Grinshpun-Cohen et al. surveyed 42 Israeli women without a medical indication for amniocentesis other than age. They found that one third of women who had a noninvasive serum screening test prior to amniocentesis did not even wait for the test results before electing to have the invasive procedure and 10 % of women did not have any serum screening test prior to amniocentesis. There may be multiple reasons why women of advanced maternal age are not integrating screening risk information into their decision making about amniocentesis. However, our understanding of those reasons is limited, as we don't have information on the content of conversations between health care providers and women who are considering amniocentesis. We don't know if health care providers counseled women on how screening risk information can inform their decision about whether or not to purse a diagnostic amniocentesis. Even if women with screening tests results suggestive of a low risk of Down syndrome were counseled not to pursue an amniocentesis, some women may have a preference for diagnostic information about a fetus's Down syndrome status. Health care providers should, however, be encouraged to engage women in a process of shared decision making to ensure that women are informed and making deliberative decisions that meet their goals of care. Offering women a relatively new, cell-free fetal DNA test may provide reassurance that negates the impulse to have an amniocentesis. Public funding for amniocentesis for all women of advanced maternal age should continue as the decision to purse an amniocentesis is best determined by women who have to live with the consequences of their choice. PMID- 26855765 TI - Alternating bipolar field stimulation identifies muscle fibers with defective excitability but maintained local Ca(2+) signals and contraction. AB - BACKGROUND: Most cultured enzymatically dissociated adult myofibers exhibit spatially uniform (UNI) contractile responses and Ca(2+) transients over the entire myofiber in response to electric field stimuli of either polarity applied via bipolar electrodes. However, some myofibers only exhibit contraction and Ca(2+) transients at alternating (ALT) ends in response to alternating polarity field stimulation. Here, we present for the first time the methodology for identification of ALT myofibers in primary cultures and isolated muscles, as well as a study of their electrophysiological properties. RESULTS: We used high-speed confocal microscopic Ca(2+) imaging, electric field stimulation, microelectrode recordings, immunostaining, and confocal microscopy to characterize the properties of action potential-induced Ca(2+) transients, contractility, resting membrane potential, and staining of T-tubule voltage-gated Na(+) channel distribution applied to cultured adult myofibers. Here, we show for the first time, with high temporal and spatial resolution, that normal control myofibers with UNI responses can be converted to ALT response myofibers by TTX addition or by removal of Na(+) from the bathing medium, with reappearance of the UNI response on return of Na(+). Our results suggest disrupted excitability as the cause of ALT behavior and indicate that the ALT response is due to local depolarization-induced Ca(2+) release, whereas the UNI response is triggered by action potential propagation over the entire myofiber. Consistent with this interpretation, local depolarizing monopolar stimuli give uniform (propagated) responses in UNI myofibers, but only local responses at the electrode in ALT myofibers. The ALT responses in electrically inexcitable myofibers are consistent with expectations of current spread between bipolar stimulating electrodes, entering (hyperpolarizing) one end of a myofiber and leaving (depolarizing) the other end of the myofiber. ALT responses were also detected in some myofibers within intact isolated whole muscles from wild-type and MDX mice, demonstrating that ALT responses can be present before enzymatic dissociation. CONCLUSIONS: We suggest that checking for ALT myofiber responsiveness by looking at the end of a myofiber during alternating polarity stimuli provides a test for compromised excitability of myofibers, and could be used to identify inexcitable, damaged or diseased myofibers by ALT behavior in healthy and diseased muscle. PMID- 26855768 TI - Chromosomal rearrangements, phenotypic variation and modularity: a case study from a contact zone between house mouse Robertsonian races in Central Italy. AB - The Western European house mouse, Mus musculus domesticus, is well-known for the high frequency of Robertsonian fusions that have rapidly produced more than 50 karyotipic races, making it an ideal model for studying the mechanisms of chromosomal speciation. The mouse mandible is one of the traits studied most intensively to investigate the effect of Robertsonian fusions on phenotypic variation within and between populations. This complex bone structure has also been widely used to study the level of integration between different morphogenetic units. Here, with the aim of testing the effect of different karyotypic assets on the morphology of the mouse mandible and on its level of modularity, we performed morphometric analyses of mice from a contact area between two highly metacentric races in Central Italy. We found no difference in size, while the mandible shape was found to be different between the two Robertsonian races, even after accounting for the genetic relationships among individuals and geographic proximity. Our results support the existence of two modules that indicate a certain degree of evolutionary independence, but no difference in the strength of modularity between chromosomal races. Moreover, the ascending ramus showed more pronounced interpopulation/race phenotypic differences than the alveolar region, an effect that could be associated to their different polygenic architecture. This study suggests that chromosomal rearrangements play a role in the house mouse phenotypic divergence, and that the two modules of the mouse mandible are differentially affected by environmental factors and genetic makeup. PMID- 26855769 TI - Sperm performance in conspecific and heterospecific female fluid. AB - Divergent sexual selection within allopatric populations may result in divergent sexual phenotypes, which can act as reproductive barriers between populations upon secondary contact. This hypothesis has been most tested on traits involved in precopulatory sexual selection, with less work focusing on traits that act after copulation and before fertilization (i.e., postcopulatory prezygotic traits), particularly in internally fertilizing vertebrates. However, postcopulatory sexual selection within species can also drive trait divergence, resulting in reduced performance of heterospecific sperm within the female reproductive tract. Such incompatibilities, arising as a by-product of divergent postcopulatory sexual selection in allopatry, can represent reproductive barriers, analogous to species-assortative mating preferences. Here, we tested for postcopulatory prezygotic reproductive barriers between three pairs of taxa with diverged sperm phenotypes and moderate-to-high opportunity for postcopulatory sexual selection (barn swallows Hirundo rustica versus sand martins Riparia riparia, two subspecies of bluethroats, Luscinia svecica svecica versus L. s. namnetum, and great tits Parus major versus blue tits Cyanistes caeruleus). We tested sperm swimming performance in fluid from the outer reproductive tract of females, because the greatest reduction in sperm number in birds occurs as sperm swim across the vagina. Contrary to our expectations, sperm swam equally well in fluid from conspecific and heterospecific females, suggesting that postcopulatory prezygotic barriers do not act between these taxon pairs, at this stage between copulation and fertilization. We therefore suggest that divergence in sperm phenotypes in allopatry is insufficient to cause widespread postcopulatory prezygotic barriers in the form of impaired sperm swimming performance in passerine birds. PMID- 26855770 TI - A novel mutation in CELSR1 is associated with hereditary lymphedema. AB - BACKGROUND: Biological evidence reported in the literature supports the role of CELSR1 as being essential for valvular function in murine lymphatics. Yet thus far, there have been no variants in CELSR1 associated with lymphatic dysfunction in humans. CASE PRESENTATION: In this report, a rare early inactivating mutation in CELSR1 is found to be causal for non-syndromic, lower extremity lymphedema in a family across three generations. Near-infrared fluorescence lymphatic imaging shows that instead of being propelled within the lumen of well-defined lymphatic vessels, lymph moved in regions of both legs in an unusual fashion and within sheet-like structures. CONCLUSION: CELSRI may be responsible for primary, non syndromic lymphedema in humans. PMID- 26855771 TI - A biophysical model of supercoiling dependent transcription predicts a structural aspect to gene regulation. AB - BACKGROUND: Transcription in Escherichia coli generates positive supercoiling in the DNA, which is relieved by the enzymatic activity of gyrase. Recently published experimental evidence suggests that transcription initiation and elongation are inhibited by the buildup of positive supercoiling. It has therefore been proposed that intermittent binding of gyrase plays a role in transcriptional bursting. Considering that transcription is one of the most fundamental cellular processes, it is desirable to be able to account for the buildup and release of positive supercoiling in models of transcription. RESULTS: Here we present a detailed biophysical model of gene expression that incorporates the effects of supercoiling due to transcription. By directly linking the amount of positive supercoiling to the rate of transcription, the model predicts that highly transcribed genes' mRNA distributions should substantially deviate from Poisson distributions, with enhanced density at low mRNA copy numbers. Additionally, the model predicts a high degree of correlation between expression levels of genes inside the same supercoiling domain. CONCLUSIONS: Our model, incorporating the supercoiling state of the gene, makes specific predictions that differ from previous models of gene expression. Genes in the same supercoiling domain influence the expression level of neighboring genes. Such structurally dependent regulation predicts correlations between genes in the same supercoiling domain. The topology of the chromosome therefore creates a higher level of gene regulation, which has broad implications for understanding the evolution and organization of bacterial genomes. PMID- 26855772 TI - Basal body structure and composition in the apicomplexans Toxoplasma and Plasmodium. AB - The phylum Apicomplexa encompasses numerous important human and animal disease causing parasites, including the Plasmodium species, and Toxoplasma gondii, causative agents of malaria and toxoplasmosis, respectively. Apicomplexans proliferate by asexual replication and can also undergo sexual recombination. Most life cycle stages of the parasite lack flagella; these structures only appear on male gametes. Although male gametes (microgametes) assemble a typical 9+2 axoneme, the structure of the templating basal body is poorly defined. Moreover, the relationship between asexual stage centrioles and microgamete basal bodies remains unclear. While asexual stages of Plasmodium lack defined centriole structures, the asexual stages of Toxoplasma and closely related coccidian apicomplexans contain centrioles that consist of nine singlet microtubules and a central tubule. There are relatively few ultra-structural images of Toxoplasma microgametes, which only develop in cat intestinal epithelium. Only a subset of these include sections through the basal body: to date, none have unambiguously captured organization of the basal body structure. Moreover, it is unclear whether this basal body is derived from pre-existing asexual stage centrioles or is synthesized de novo. Basal bodies in Plasmodium microgametes are thought to be synthesized de novo, and their assembly remains ill-defined. Apicomplexan genomes harbor genes encoding delta- and epsilon-tubulin homologs, potentially enabling these parasites to assemble a typical triplet basal body structure. Moreover, the UNIMOD components (SAS6, SAS4/CPAP, and BLD10/CEP135) are conserved in these organisms. However, other widely conserved basal body and flagellar biogenesis elements are missing from apicomplexan genomes. These differences may indicate variations in flagellar biogenesis pathways and in basal body arrangement within the phylum. As apicomplexan basal bodies are distinct from their metazoan counterparts, it may be possible to selectively target parasite structures in order to inhibit microgamete motility which drives generation of genetic diversity in Toxoplasma and transmission for Plasmodium. PMID- 26855773 TI - A perioperative consult service results in reduction in cost and length of stay for colorectal surgical patients: evidence from a healthcare redesign project. AB - BACKGROUND: A major restructuring of perioperative care delivery is required to reduce cost while improving patient outcomes. In a test implementation of this notion, we developed and implemented a perioperative consult service (PCS) for colorectal surgery patients. METHODS: A 6-month planning process was undertaken to engage key stakeholders from surgery, nursing, and anesthesia in a healthcare redesign project that resulted in the creation of a PCS to implement a coordinated clinical pathway. After Institutional Review Board (IRB) approval, data were collected for all elective colorectal procedures for three phases: phase 0 (pre-implementation; 1/2014-6/2014), phase 1 (7/2014-10/2014), and phase 2 (11/2014-10/2015). Length of stay (primary endpoint; LOS), total hospital cost, use of clinical pathway components, markers of functional recovery, and readmission and reoperation rates were analyzed. Outcomes and patient characteristics among phases were compared by two-tailed t tests and Wilcoxon rank-sum tests. Categorical variables were analyzed by chi-square and Fisher's exact tests. RESULTS: We studied 544 patients (phase 0 = 179; phase 1 = 124; phase 2 = 241), with 365 consecutive patients being cared for in the redesigned care structure. Median LOS was reduced and sustained after implementation (phase 0, 4.24 days; phase 1, 3.32 days; phase 2, 3.32 days, P < 0.01 phase 0 v. phases 1 and 2), and mean LOS was reduced in phase 2 (phase 0, 5.26 days; phase 1, 4.93 days; phase 2, 4.36 days, P < 0.01 phase 0 v. phase 2). Total hospital cost was reduced by 17 % (P = 0.05, median). Application of clinical pathway components was higher in phases 1 and 2 compared to phase 0 (P < 0.01 for all components except anti-emetics); measures of functional recovery improved with successive phases. Reoperation and 30-day readmission rates were no different in phase 1 or phase 2 compared to phase 0 (P > 0.15). CONCLUSIONS: Restructuring of perioperative care delivery through the launch of a PCS-reduced LOS and total cost in a significant and sustainable fashion for colorectal surgery patients. Based on the success of this care redesign project, hospital administration is funding expansion to additional services. PMID- 26855774 TI - Postprandial thermogenesis and respiratory quotient in response to galactose: comparison with glucose and fructose in healthy young adults. AB - Circumstantial evidence suggests that substitution of glucose or sucrose by the low-glycaemic index sugar galactose in the diet may lead to greater thermogenesis and/or fat oxidation. Using ventilated hood indirect calorimetry, we investigated, in twelve overnight-fasted adults, the resting energy expenditure (REE) and respiratory quotient (RQ) for 30 min before and 150 min after ingestion of 500 ml of water containing 60 g of glucose, fructose or galactose in a randomised cross-over design. REE increased similarly with all three sugars, reaching peak values after 50-60 min, but its subsequent fall towards baseline values was faster with galactose and glucose than with fructose (P < 0.001). RQ increased with all three sugars, but to a much greater extent with galactose and fructose than with glucose, particularly after 1 h post-ingestion. When ingested as a sugary drink, postprandial thermogenesis and utilisation of fat after galactose are not higher than after glucose or fructose. PMID- 26855775 TI - Reproducibility of a web-based FFQ for 13- to 15-year-old Danish adolescents. AB - FFQ are widely used in large-scale studies to assess dietary intake. To aid interpretation of diet-disease associations assessment of validity must be performed. Reproducibility is one aspect of validity focusing on the stability of repeated assessment with the same method which may also reveal problems in instrument design or participant instructions. The aim of the present study was to evaluate the reproducibility of a web-based FFQ targeting Danish adolescents within the Danish National Birth Cohort (DNBC). Data for the present study were obtained from a prospective design nested within the DNBC. Adolescents aged 13 to 15 years old (n 48, 60 % girls) completed the FFQ twice 4 weeks apart. The proportion of adolescents consistently classified into the same tertile according to amount of food intake ranged from 45 % (fish) to 77 % (vegetables), whereas classification into opposite tertiles ranged from 0 % (fruit, oils and dressing) to 15 % (beverages). Overall, no significant differences were observed in intake of food groups or nutrients between the two completions of the FFQ. Mean crude Spearman correlation for all food groups was 0.56 and mean intra-class correlation for all food groups was 0.61. In conclusion, the reproducibility of the FFQ for Danish adolescents was acceptable. The study revealed that adolescents aged 13-15 years seemed capable of recalling consistently overall dietary habits and had some difficulties estimating the frequency of consumption of regularly consumed food items. PMID- 26855776 TI - Comparative proteomic analysis of the effects of high-concentrate diet on the hepatic metabolism and inflammatory response in lactating dairy goats. AB - BACKGROUND: To understand the impact of feeding a high-concentrate diet to mid lactating goats for a long time on liver metabolism and inflammatory response, two dimensional polyacrylamide gel electrophoresis (2-DE) and real-time PCR method were employed to detect proteins differentially expressed in liver and their mRNAs expression in goats fed high concentrate diet (HC) or low concentrate diet (LC). Twelve lactating dairy goats were randomly assigned to either a HC diet group (65 % concentrate of dry matter; n = 6) or a LC diet group (35 % concentrate of dry matter; n = 6) for 10 wk. RESULTS: Twenty differentially expressed spots (>=2.0-fold changes) in the hepatic tissues were excised and successfully identified using MALDI TOF/TOF. Of these, 8 proteins were up regulated, while the rest 12 proteins were down-regulated in HC goats compared to LC. Differential expressed proteins including alpha enolase 1 (ENO1), glutamate dehydrogenase 1 (GLUD1), glutathione S-transferase A1 (GSTA1), ATP synthase subunit 5beta (ATP5beta), superoxide dismutase [Cu-Zn] (SOD1), cytochrom c oxidase subunit Via (COX6A1) and heat shock protein 60 (HSP60) were further verified by real-time PCR and/or western blot at mRNA or protein expression level. Consistent with the 2-DE results, a significant decrease of beta-actin protein expression and SOD enzyme activity was observed in liver of HC goats (P < 0.05), while ENO1 protein expression was significantly up-regulated in HC compared to LC goats (P < 0.05) . However, western blot analysis did not show a significant difference of hepatic HSP60 protein between HC and LC group, which did not match the decrease of HSP60 content detected by 2-DE analysis. Real-time PCR showed that glutathione S-transferase P1 (GSTP1) and SOD1 mRNA expression was significantly decreased in liver of HC goats, while cytochrom c oxidase (COX3) and ATPase 8 (ATP8) mRNAs expression were markedly increased compared to LC (P < 0.05). Gene Ontology (GO) analysis revealed that HC diet resulted in altered expression of proteins related to catalytic and mitochondrial metabolism in the liver, and may increase the stress response with up-regulating the expression of differentiation 14 (CD14) cluster and serum amyloid A (SAA) as well as C-reactive protein (CRP) in the liver. CONCLUSIONS: These results suggest that feeding high concentrate diet to lactating goats for 10 wk leads to the activation of the inflammatory response, and decreases the anti-oxidant capacity, and subsequently impairs the mitochondrial function in the liver. PMID- 26855607 TI - Measurement of differential cross sections for Higgs boson production in the diphoton decay channel in pp collisions at [Formula: see text]. AB - A measurement is presented of differential cross sections for Higgs boson (H) production in pp collisions at [Formula: see text][Formula: see text]. The analysis exploits the [Formula: see text] decay in data corresponding to an integrated luminosity of 19.7[Formula: see text] collected by the CMS experiment at the LHC. The cross section is measured as a function of the kinematic properties of the diphoton system and of the associated jets. Results corrected for detector effects are compared with predictions at next-to-leading order and next-to-next-to-leading order in perturbative quantum chromodynamics, as well as with predictions beyond the standard model. For isolated photons with pseudorapidities [Formula: see text], and with the photon of largest and next-to largest transverse momentum ([Formula: see text]) divided by the diphoton mass [Formula: see text] satisfying the respective conditions of [Formula: see text] and [Formula: see text], the total fiducial cross section is [Formula: see text][Formula: see text]. PMID- 26855778 TI - A clinical profile of compulsive exercise in adolescent inpatients with anorexia nervosa. AB - BACKGROUND: The aim of the current study was to contribute to the development of a clinical profile of compulsive exercise in adolescents with Anorexia Nervosa (AN), by examining associations between compulsive exercise and eating and general psychopathology. METHOD: A sample of 60 female adolescent inpatients with AN completed a self-report measure of compulsive exercise and a series of standardized self-report questionnaires assessing eating and general psychopathology. RESULTS: Higher levels of compulsive exercise were associated with increased levels of eating disorder psychopathology and anxiety. Specifically, the avoidance aspect (negatively reinforced) of compulsive exercise was associated with elevated scores on measures of eating disorder, anxiety, depression, and obsessive compulsiveness psychopathology, as well as lower self esteem scores. The mood improvement value (positively reinforced) of compulsive exercise, however, did not reflect such trends. CONCLUSIONS: Compulsive exercise driven by avoidance of negative affect is associated with more severe psychological features in adolescent inpatients with AN. The current findings emphasize the need for research and clinical efforts in the development of treatments addressing avoidance of negative affect and compulsive exercise in adolescents with AN. PMID- 26855777 TI - N-acetylcysteine in COPD: why, how, and when? AB - Oxidants have long been recognized to have an important role in the pathogenesis of COPD, and in this cigarette smoke has a strong responsibility, because it generates a conspicuous amount of oxidant radicals able to modify the structure of the respiratory tract and to enhance several mechanisms that sustain lung inflammation in COPD. In fact, oxidative stress is highly increased in COPD and natural antioxidant capacities, mainly afforded by reduced glutathione, are often overcome. Thus an exogenous supplementation of antioxidant compounds is mandatory to at least partially counteract the oxidative stress. For this purpose N acetylcysteine has great potentialities due to its capacity of directly contrasting oxidants with its free thiols, and to the possibility it has of acting as donor of cysteine precursors aimed at glutathione restoration. Many studies in vitro and in vivo have already demonstrated the antioxidant capacity of NAC. Many clinical studies have long been performed to explore the efficacy of NAC in COPD with altern results, especially when the drug was used at very low dosage and/or for a short period of time. More recently, several trials have been conducted to verify the appropriateness of using high-dose NAC in COPD, above all to decrease the exacerbations rate. The results have been encouraging, even if some of the data come from the most widely sized trials that have been conducted in Chinese populations. Although other evidence should be necessary to confirm the results in other populations of patients, high-dose oral NAC nevertheless offers interesting perspectives as add-on therapy for COPD patients. PMID- 26855779 TI - Effects of Silicon on Osteoclast Cell Mediated Degradation, In Vivo Osteogenesis and Vasculogenesis of Brushite Cement. AB - Calcium phosphate cements (CPCs) are being widely used for treating small scale bone defects. Among the various CPCs, brushite (dicalcium phosphate dihydrate, DCPD) cement is widely used due to its superior solubility and ability to form new bone. In the present study, we have studied the physical, mechanical, osteoclast-like-cells differentiation and in vivo osteogenic and vasculogenic properties of silicon (Si) doped brushite cements. Addition of Si did not alter the phase composition of final product and regardless of Si level, all samples included beta-tricalcium phosphate (beta-TCP) and DCPD. 1.1 wt. % Si addition increased the compressive strength of undoped brushite cement from 4.78+/-0.21 MPa to 5.53+/-0.53 MPa, significantly. Cellular activity was studied using receptor activator of nuclear factor kappabeta ligand (RANKL) supplemented osteoclast-like-cells precursor RAW 264.7 cell. Phenotypic expressions of the cells confirmed successful differentiation of RAW264.7 monocytes to osteoclast like-cells on undoped and doped brushite cements. An increased activity of osteoclast-like cells was noticed due to Si doping in the brushite cement. An excellent new bone formation was found in all cement compositions, with significant increase in Si doped brushite samples as early as 4 weeks post implantation in rat femoral model. After 4 weeks of implantation, no significant difference was found in blood vessel formation between the undoped and doped cements, however, a significant increase in vasculgenesis was found in 0.8 and 1.1 wt. % Si doped brushite cements after 8 weeks. These results show the influence of Si dopant on physical, mechanical, in vitro osteoclastogenesis and in vivo osteogenic and vasculogenic properties of brushite cements. PMID- 26855781 TI - Ruxolitinib improves symptoms and quality of life in a patient with systemic mastocytosis. AB - BACKGROUND: Systemic mastocytosis is a clonal myeloproliferative neoplasm associated with constitutional symptoms from mast cell mediated chemical and cytokine release. According to the literature, Ruxolitinib, a JAK1/JAK2 inhibitor, has been shown to reduce symptoms related to proinflammatory cytokine release in other myeloproliferative neoplasms. CASE PRESENTATION: Here we present a case using Ruxolitinib for disabling constitutional symptoms despite complete bone marrow response in a patient with aggressive systemic mastocytosis. Assessment tools used to monitor symptoms in previously published Ruxolitinib trials were adopted to track symptom improvement and quality of life. CONCLUSIONS: Ruxolitinib significantly improved symptoms and quality of life in our patient with systemic mastocytosis. PMID- 26855783 TI - Drug-related problems and potential contributing factors in the management of deep vein thrombosis. AB - BACKGROUND: Patients receiving anticoagulant drugs must be carefully screened for drug-related problems, as such medications, including warfarin have narrow therapeutic ranges and a high potential for complications. Thus, this study was designed to assess drug-related problems in the management of patients with deep vein thrombosis at Tikur Anbessa Specialized Hospital. METHODS: A cross-sectional descriptive study involving retrospective chart review of adult patients with deep vein thrombosis was conducted from patients who visited the hospital from July 2012 to June 2013, using structured data collection format and this was complemented by key informant interview. RESULTS: The study included 91 patients with venous thromboembolism. Fifty three (58.2 %) were females. Mean age was 38.6 (+/-13.76) years and more than 2/3 were below the age of 44 years. About 54 % of them presented with concurrent medical conditions and most commonly with cancer. Adjustment of warfarin dose up or down was done in increments of 16 to 100 % for recent subtherapeutic International Normalized Ratios, 16 to 50 % for therapeutic and 11 to 66 % for overtherapeutic International Normalized Ratios, with the mean of 36.5 (+/-18.03) based on the cumulative weekly dose of warfarin. There was significant linear relationship between percentage of dose change and consequent International Normalized Ratio values (R(2) = 0.419; p = 0.000). Accordingly, more than 51 % of them presented with nontherapeutic International Normalized Ratio ranges following dose adjustment. CONCLUSIONS: The most prevalent anticoagulation drug-related problems were subtherapeutic doses, overtherapeutic doses and potential drug interactions. Institutional validated decision support tools for dosing decisions during maintenance anticoagulation therapy should be developed and used accordingly in order to prevent recurrent and hemorrhagic complications and to improve clinical outcomes. PMID- 26855782 TI - Anabolic steroids abuse and male infertility. AB - For several decades, testosterone and its synthetic derivatives have been used with anabolic and androgenic purposes. These substances were first restricted to professional bodybuilders, but become more and more popular among recreational athletes. Up to date, 3,000,000 anabolic-androgenic steroids (AAS) users have been reported in the United States with an increasing prevalence, making AAS consumption a major public health growing concern. Infertility is defined by the WHO as the failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse and a male factor is present in up to 50 % of all infertile couples. Several conditions may be related to male infertility. Substance abuse, including AAS, is commonly associated to transient or persistent impairment on male reproductive function, through different pathways. Herein, a brief overview on AAS is offered. Steroids biochemistry, patterns of use, physiological and clinical issues are enlightened. A further review about fertility outcomes among male AAS abusers is also presented, including the classic reports on transient anabolic steroid-induced hypogonadism (ASIH), and the more recent experimental reports on structural and genetic sperm damage. PMID- 26855784 TI - Comparison of three activity monitors for estimating sedentary time among children. AB - BACKGROUND: Time spent sedentary appears to be associated with several health outcomes in adults, but findings are inconsistent in children. Further, the assessment of sedentary time represents a major challenge. The objectives of the present study were to determine whether 1) ActiGraph GT3X+, ActivPAL and SenseWear Armband Pro3 (SWA) provide comparable estimates of sedentary time in 9 12-year-old children, 2) these devices are valid compared with direct observation, and 3) ActivPAL discriminates between sitting and standing behavior. METHODS: The sample was 67 children. Data were collected during three consecutive days in November 2012. To test the activity monitors in contexts related to physical and sedentary activities commonly performed by children, the children participated in sessions of activity while sitting (watching television, playing video games and tossing a ball while sitting) and standing (musical chairs, active video gaming and tossing a ball) while wearing three different activity monitors at the same time. All activity sessions were observed by two researchers. Differences between monitors were determined using Friedman's two way analysis of variance by rank order. RESULTS: Minutes of estimated sedentary time differed across device brands during combined sitting activities: SWA vs. ActiGraph GT3X+ (P = 0.048), SWA vs. ActivPAL, (P < 0.001) and ActiGraph GT3X+ vs. ActivPAL (P = 0.002). Out of 12 min in total of combined recorded sitting activity, SWA reported a median of 6 min (95 % Confidence Interval [CI] = 5.0, 7.0), ActiGraph GT3X+ 7 min (7.0, 8.0) and ActivPAL 10 min (8.6, 10.8) as sedentary time. ActivPAL recorded 3.7 (2.4, 4.0) minutes of the non-sitting activities 'musical chairs', 4.0 (4.0, 4.0) minutes in 'standing ball toss'; and 4.0 (2.7, 4.0) minutes in 'active video gaming' as sitting time. CONCLUSION: Recorded sedentary time varied among the monitors GT3X+, SWA and ActivPAL, and misclassification of standing activities as sitting activities were apparent for ActivPAL in certain activities. PMID- 26855780 TI - Light-Sensitive Ruthenium Complex-Loaded Cross-linked Polymeric Nanoassemblies for the Treatment of Cancer. AB - This work focuses on improving the efficacy of photoactivatable Ru complexes for photodynamic therapy by employing cross-linked nanoassemblies (CNAs) as a delivery approach. The effects of complex photoactivation, hydrophobicity, and solution ionic strength and pH on complex loading and release from CNAs were analyzed. The cell cytotoxicity of CNA formulations was similar to free Ru complexes despite reduced or eliminated DNA interactions. The release rate and the amount of each Ru complex released (%) varied inversely with complex hydrophobicity, while the effect of solution ionic strength was dependent on complex hydrophobicity. Premature release of two photoactivatable prodrugs prior to irradiation was believed to account for higher activity in cells studies compared to DNA interaction studies; however, for photostable 1O2 generator loaded CNAs this cannot explain the high cytotoxicity and lack of DNA interactions because release was incomplete after 48 hrs. The cause remains unclear, but among other possibilities, accelerated release in a cell culture environment may be responsible. PMID- 26855785 TI - Estimating the proportion of metabolic health outcomes attributable to obesity: a cross-sectional exploration of body mass index and waist circumference combinations. AB - BACKGROUND: Recent evidence suggests that a substantial subgroup of the population who have a high-risk waist circumference (WC) do not have an obese body mass index (BMI). This study aimed to explore whether including those with a non-obese BMI but high risk WC as 'obese' improves prediction of adiposity related metabolic outcomes. METHODS: Eleven thousand, two hundred forty-seven participants were recruited. Height, weight and WC were measured. Ten thousand, six hundred fifty-nine participants with complete data were included. Adiposity categories were defined as: BMI(N)/WC(N), BMI(N)/WC(O), BMI(O)/WC(N), and BMI(O)/WC(O) (N = non-obese and O = obese). Population attributable fraction, area under the receiver operating characteristic curve (AUC), and odds ratios (OR) were calculated. RESULTS: Participants were on average 48 years old and 50 % were men. The proportions of BMI(N)/WC(N), BMI(N)/WC(O), BMI(O)/WC(N) and BMI(O)/WC(O) were 68, 12, 2 and 18 %, respectively. A lower proportion of diabetes was attributable to obesity defined using BMI alone compared to BMI and WC combined (32 % vs 47 %). AUC for diabetes was also lower when obesity was defined using BMI alone (0.62 vs 0.66). Similar results were observed for all outcomes. The odds for hypertension, dyslipidaemia, diabetes and CVD were increased for those with BMI(N)/WC(O) (OR range 1.8-2.7) and BMI(O)/WC(O) (OR 1.9 4.9) compared to those with BMI(N)/WC(N). CONCLUSIONS: Current population monitoring, assessing obesity by BMI only, misses a proportion of the population who are at increased health risk through excess adiposity. Improved identification of those at increased health risk needs to be considered for better prioritisation of policy and resources. PMID- 26855787 TI - Effect of feeding a by-product feed-based silage on nutrients intake, apparent digestibility, and nitrogen balance in sheep. AB - BACKGROUND: Literature is lacking on the effects of feeding by-product feed (BF) based silage on rumen fermentation parameters, nutrient digestion and nitrogen (N) retention in sheep. Therefore, this study was conducted to determine the effect of replacing rye straw with BF-based silage as a roughage source on ruminal parameters, total-tract apparent nutrient digestibility, and N balance in sheep. METHODS: The by-product feed silage was composed of spent mushroom substrate (SMS) (45 %), recycled poultry bedding (RPB) (21 %), rye straw (11 %), rice bran (10.8 %), corn taffy residue (10 %), protected fat (1.0 %), bentonite (0.6 %), and mixed microbial additive (0.6 %). Six sheep were assigned randomly to either the control (concentrate mix + rye straw) or a treatment diet (concentrate mix + BF-based silage). RESULTS: Compared with the control diet, feeding a BF-based silage diet resulted in similar ruminal characteristics (pH, acetate, propionate, and butyrate concentrations, and acetate: propionate ratio), higher (p < 0.05) ruminal NH3-N, higher (p < 0.05) ether extract digestibility, similar crude protein digestibility, lower (p < 0.05) dry matter, fiber, and crude ash digestibilities, and higher (p < 0.05) N retention (g/d). CONCLUSION: The BF-based silage showed similar energy value, higher protein metabolism and utilization, and lower fiber digestion in sheep compared to the control diet containing rye straw. PMID- 26855786 TI - Military service and other socioecological factors influencing weight and health behavior change in overweight and obese Veterans: a qualitative study to inform intervention development within primary care at the United States Veterans Health Administration. AB - BACKGROUND: Obesity affects 37 % of patients at Veterans Health Administration (VHA) medical centers. The VHA offers an intensive weight management program (MOVE!) but less than 10 % of eligible patients ever attend. However, VHA patients see their primary care provider about 3.6 times per year, supporting the development of primary care-based weight management interventions. To address gaps in the literature regarding Veterans' experiences with weight management and determine whether and how to develop a primary care-based weight management intervention to both improve obesity counseling and increase attendance to MOVE!, we conducted a qualitative study to assess: 1) Veterans' personal experiences with healthy weight-related behavior change (including barriers and facilitators to behavior change and experiences with primary care providers, staff, and the MOVE! program), and 2) potential new approaches to improve weight management within primary care at the VHA including goal setting and technology. METHODS: Overweight/obese VHA patients (aged 18-75, BMI greater than 30 or greater than 25 with at least 1 co-morbidity) were recruited for focus group sessions stratified by gender, MOVE! referral, and attendance. Each session was facilitated by a trained moderator, audio-recorded, and professionally transcribed. Using an iterative coding approach, two coders separately reviewed and coded transcripts, and met frequently to negotiate codes and synthesize emerging themes. RESULTS: Of 161 eligible patients, 54 attended one of 6 focus groups (2 female, 4 male, 9-11 participants per session): 63 % were male, 46 % identified as African-American, 32 % White/Caucasian, 74 % were college-educated or higher, and 61 % reported having attended MOVE!. We identified two major themes: Impact of Military Service and Promotion and Sustainability of Healthy Behaviors. After service in a highly structured military environment, Veterans had difficulty maintaining weight on their own. They perceived physical activity as having more impact than diet, but chronic pain was a barrier. We identified individual/interpersonal-, community/environment-, and healthcare system-related factors affecting healthy behaviors. We also received input about Veteran's preferences and experiences with technology and setting health goals. CONCLUSIONS: Unique factors influence weight management in Veterans. Findings will inform development of a technology assisted weight management intervention with tailored counseling and goal-setting within primary care at the VHA. PMID- 26855788 TI - Biofilm-associated bacterial amyloids dampen inflammation in the gut: oral treatment with curli fibres reduces the severity of hapten-induced colitis in mice. AB - BACKGROUND/OBJECTIVES: A disruption of epithelial barrier function can lead to intestinal inflammation. Toll-like receptor (TLR) 2 activation by microbial products promotes intestinal epithelial integrity and overall gut health. Several bacterial species, including enteric bacteria, actively produce amyloid proteins as a part of their biofilms. Recognition of amyloid fibres found in enteric biofilms, termed curli, by the Toll-like receptor (TLR)2/1 complex reinforces barrier function. Here, we investigated the effect of purified curli fibres on inflammation in a mouse model of acute colitis. METHODS: Bone marrow-derived macrophages as well as lamina propria cells were treated with curli fibres of both pathogenic Salmonella enterica serovar Typhimurium and commensal Escherichia coli Nissle 1917 biofilms. Mice were given 0.1 or 0.4 mg of purified curli orally 1 day post administration of 1% 2,4,6-trinitrobenzene sulphonic acid (TNBS) enema. Histopathological analysis was performed on distal colonic tissue taken 6 days post TNBS enema. RNA extracted from colonic tissue was subjected to RT-PCR. RESULTS: Here we show that curli fibres of both pathogenic and commensal bacteria are recognised by TLR2 leading to the production of IL-10, immunomodulatory cytokine of intestinal homeostasis. Treatment of mice with a single dose of curli heightens transcript levels of Il10 in the colon and ameliorates the disease pathology in TNBS-induced colitis. Curli treatment is comparable to the treatment with anti-tumour necrosis factor alpha (anti-TNFalpha) antibodies, a treatment known to reduce the severity of acute colitis in humans and mice. CONCLUSION: These results suggest that the bacterial amyloids had a role in helping to maintain immune homeostasis in the intestinal mucosa via the TLR2/IL-10 axis. Furthermore, bacterial amyloids may be a potential candidate therapeutic to treat intestinal inflammatory disorders owing to their remarkable immunomodulatory activity. PMID- 26855789 TI - Amphioxus mouth after dorso-ventral inversion. AB - INTRODUCTION: Deuterostomes (animals with 'secondary mouths') are generally accepted to develop the mouth independently of the blastopore. However, it remains largely unknown whether mouths are homologous among all deuterostome groups. Unlike other bilaterians, in amphioxus the mouth initially opens on the left lateral side. This peculiar morphology has not been fully explained in the evolutionary developmental context. We studied the developmental process of the amphioxus mouth to understand whether amphioxus acquired a new mouth, and if so, how it is related to or differs from mouths in other deuterostomes. RESULTS: The left first somite in amphioxus produces a coelomic vesicle between the epidermis and pharynx that plays a crucial role in the mouth opening. The vesicle develops in association with the amphioxus-specific Hatschek nephridium, and first opens into the pharynx and then into the exterior as a mouth. This asymmetrical development of the anterior-most somites depends on the Nodal-Pitx signaling unit, and the perturbation of laterality-determining Nodal signaling led to the disappearance of the vesicle, producing a symmetric pair of anterior-most somites that resulted in larvae lacking orobranchial structures. The vesicle expressed bmp2/4, as seen in ambulacrarian coelomic pore-canals, and the mouth did not open when Bmp2/4 signaling was blocked. CONCLUSIONS: We conclude that the amphioxus mouth, which uniquely involves a mesodermal coelomic vesicle, shares its evolutionary origins with the ambulacrarian coelomic pore-canal. Our observations suggest that there are at least three types of mouths in deuterostomes, and that the new acquisition of chordate mouths was likely related to the dorso-ventral inversion that occurred in the last common ancestor of chordates. PMID- 26855790 TI - Nitric oxide generating/releasing materials. AB - Harnessing the impressive therapeutic potential of nitric oxide (NO) remains an ongoing challenge. This paper describes several of the current strategies both with respect to the underlying chemistry and physics and to the applications where they have shown promise. Included in this overview are molecular systems such as NONOates that release NO through chemical reactions and delivery vehicles such as nanoparticles that can generate, store, transport and deliver NO and related bioactive forms of NO such as nitrosothiols. Although there has been much positive movement, it is clear that we are only at the early stages of knowing how to precisely produce, transport and deliver to targeted sites therapeutic levels of NO and related molecules. PMID- 26855791 TI - Predictive factors for biochemical recurrence in radical prostatectomy patients. AB - INTRODUCTION: Radical prostatectomy (RP) is considered the best treatment for the management of localized prostate cancer in patients with life expectancy over 10 years. However, a complete recovery is not guaranteed for all patients who received/underwent RP treatment. Biochemical recurrence is frequently observed during the post-operative follow-up period. The main objective in this study is to evaluate the predictive factors of biochemical recurrence in localized prostate cancer patients who underwent RP surgery. MATERIAL AND METHODS: The study included 352 patients with prostate cancer treated by RP at a single institution between February 2004 and June 2014. Detailed pathological and follow up data of all patients were obtained and analyzed to determine the results. RESULTS: Mean follow-up duration was 39.7 months. 83 patients (23%) experienced biochemical recurrence (BCR) during the follow-up period. Mean BCR duration range was 6.56 (1-41) months. In multivariate logistic regression analysis, Gleason score (GS), PSA and extra-capsular tumour spread (ECS) variables were found to be statistically significant as BCR predictive factors. CONCLUSIONS: According to our study results, it is thought that PSA, GS and ECS can all be used for guidance in choosing a treatment modality for post-RP biochemical recurrence and metastatic disease as predictive factors. However, there is no consensus in this matter and it is still debated. PMID- 26855792 TI - Does anterior prostatic fat tissue removed during robotic radical prostatectomy contain any lymph nodes? AB - INTRODUCTION: We investigated whether anterior periprostatic fat (APPF) tissue removed during robotic radical prostatectomy (RARP) contains any lymph nodes (LNs). MATERIAL AND METHODS: APPF tissues removed during RARP in 129 patients were evaluated histopathologically. Correlation with postoperative pathologic stage was made. Patients with a history of previous prostate or bladder surgery and radiation therapy were excluded. RESULTS: Mean patient age, serum prostate specific antigen (PSA), prostate weight and body mass index (BMI) were 62.2 +/ 5.5 (range 45-74), 9.3 +/-6.3 ng/dl (range 0.26-30.3), 60.3 +/-27.2 grams (range 11.0-180) and 26.6 +/-1.9 kg/m(2) (range 20.0-30.3), respectively. Overall, LNs in APPF tissues were detected in 14 (10.9%) patients with a mean LN yield of 1.1 +/-0.7 LNs (range, 1-3). Among those found, no metastatic LN was detected. Of the patients with pT2a (n = 22), pT2b (n = 15), pT2c (n = 62) and pT3a (n = 21) disease, LNs in APPF tissues were detected in 1 (4.6%), 1 (6.7%), 11 (17.7%) and 1 (4.8%) patient in each group, respectively. Among the patients, LNs in APPF tissues were detected in 0 (0%), 5 (35.7%), 8 (57.1%) and 1 (7.1%) patients of underweight, optimal weight, overweight and obese patients due to body mass index, respectively. CONCLUSIONS: In our series, LNs were detected in around 10% of the patients. Therefore, this fat should, not be pushed back during RARP but should be removed and sent for pathologic evaluation. Although no metastatic LN was detected in our series, the presence of metastatic LNs might have an impact on the oncologic outcomes of the patients and warrants further research. PMID- 26855793 TI - Evaluation of oxidative stress status and antioxidant capacity in patients with renal cell carcinoma. AB - INTRODUCTION: We evaluated and compared the serum oxidative stress and antioxidant enzymes in patients with renal cell carcinoma (RCC) and the control group. MATERIAL AND METHODS: The prospective study consisted of 97 patients with RCC (Group 1) and 80 age and sex matched healthy volunteers (Group 2). Group 1 and 2 were compared concerning serum mean total oxidant status (TOS), total antioxidant capacity (TAC), paraoxonase-1 (PON-1), arylesterase, total thiol, catalase (CAT), myeloperoxidase (MPO) and ceruloplasmin. RESULTS: Patients' mean age was 58.5 +/-12.3 and 56.9 +/-15.8 years, respectively, in Group 1 and 2. No statistically significant differences were detected between the groups in terms of oxidative stress parameters and antioxidant capacity measured in the serum of patients including, TOS, TAC, PON1, arylesterase, total thiol, CAT, MPO, and ceruloplasmin levels (p >0.05 for all parameters). The PON-1 value was significantly higher in patients with pT1 stage than pT3 stage (p = 0.007). The arylesterase value was significantly higher in patients with Fuhrman's nuclear grade 3 than grade 2 (p = 0.035). There was no correlation between these parameters level and Fuhrman's nuclear grade, stage, or histopathological tumor type. CONCLUSIONS: Our results demonstrated that evaluation of these parameters in the serum of patients with localized RCC may not be used as a marker to discriminate between patients with RCC and healthy people. PMID- 26855794 TI - Spectrum of retroperitoneal and genitourinary paraganglioma: Experience at a North Indian tertiary care center. AB - INTRODUCTION: Genitourinary and retroperitoneal paragangliomas are infrequent tumors with bizarre presentation. A high index of suspicion is required to make a diagnosis in young hypertensive individuals. Our aim is to study the varied clinical presentations and management of these paragangliomas. Herein, we share our experience of clinical presentation, diagnosis, and management of these paragangliomas. MATERIAL AND METHODS: Seventeen consecutive patients who underwent surgery for paraganglioma at our institute from August 2009 to July 2014 were included. Demographic, peri-operative, surgical, and follow up data were collected and analyzed. RESULTS: Mean age of presentation was 34.8 years with female predominance. The majority of the tumors were located in the retroperitoneum and urinary bladder. Most of them presented with classical symptoms of catecholamine excess and hypertension. Complete surgical resection could be performed in 13 cases. At a median follow up of two years, cases with R0 resection (no microscopic malignant cells) did not show recurrence. Among patients on chemotherapy, one died, another had partial response, and yet another had progressive disease. CONCLUSIONS: Genitourinary and retroperitoneal paragangliomas are a disease of a young age group with variable clinical features at presentation. Appropriate pre-operative optimization and complete surgical resection provide the best chance of cure. PMID- 26855795 TI - Durability, safety and efficacy of polyacrylamide hydrogel (Bulkamid((r))) in the management of stress and mixed urinary incontinence: three year follow up outcomes. AB - INTRODUCTION: There are a myriad of treatment options available for patients suffering with the increasingly prevalent condition of stress urinary incontinence (SUI). The minimally invasive nature of periurethral bulking agents makes them an attractive proposition in the correctly selected patient. There is, however, limited data available on the medium to long term safety and efficacy of this procedure. The aim of our study is to evaluate the outcomes of Polyacrylamide Hydrogel (PAHG) (Bulkamid((r))) as a periurethral bulking agent at our institution. MATERIAL AND METHODS: From 2006 to 2011, two hundred and fifty six women underwent periurethral bulking with PAHG in the management of SUI or mixed urinary incontinence (MUI). Women were assessed with at least yearly quality of life and ICIQ questionnaires. RESULTS: The majority of patients had the procedure under a local anaesthetic, with a median operative time of 9 minutes. Median follow up was 38 months. 82% of patients reported cure/significant improvement at 3 months. Importantly, this high satisfaction rate was maintained at final follow up and was reflected in both VAS and ICIQ scores. There were no reported adverse reactions and no significant safety concerns. CONCLUSIONS: We conclude that Bulkamid((r)) injection is an efficacious, minimally invasive, and safe procedure for a selected group of patients with stress incontinence. In our study, PAHG has been shown to be durable and safe. PMID- 26855796 TI - Intrarenal pressure and irrigation flow with commonly used ureteric access sheaths and instruments. AB - INTRODUCTION: Flexible ureterorenoscopy is becoming a first-line treatment for many intrarenal stones. Ureteric access sheaths are commonly used to aid access, stone removal and reduce intrarenal pressure. We evaluated the effects of two commonly used access sheaths on irrigation flow and intrarenal pressure during flexible ureterorenoscopy. We measured the effect of scope instrumentation on flow and pressure. MATERIAL AND METHODS: We utilized a 10/12F and 12/14F, 35 cm Re-TraceTM access sheath with a FlexX2 scope in a cadaveric porcine kidney. We evaluated the effect of four Nitinol baskets (1.3F, 1.5F, 1.9F, 2.2F), three different 200 um laser fibres and a hand-held pump. Measurements of irrigation flow and intrarenal pressure were recorded and compared between the different sized access sheaths. RESULTS: Flow rates varied widely between access sheaths. Without instrumentation, mean flow was 17 mls/min (10/12F access sheath), versus 33 mls/min (12/14F sheath) (p <0.0001). Increasing basket size produced a gradual reduction in flow and pressure in both access sheaths. Reassuringly, pressures were low overall (<40 cm H2O). Pressures were significantly reduced when using the larger 12/14F sheath, with and without all instrumentations (p <0.0001). Hand held pump devices have a marked effect on flow and pressure in both sheaths; with pressures rising up to 121 cm H2O with a 10/12F sheath, versus 29 cm H2O (12/14F) (p <0.0001). CONCLUSIONS: A 12/14F access sheath offered significantly improved irrigation whilst maintaining significantly lower intrarenal pressure, when compared to a 10/12F access sheath in a cadaveric porcine model. Scope instrumentation affects irrigation flow and pressure in both sized sheaths. Furthermore, there should be caution with hand-held pump devices, especially with smaller sized sheaths, as intrarenal pressure can be very high. PMID- 26855797 TI - Tips and tricks of ureteroscopy: consensus statement Part I. Basic ureteroscopy. AB - Ureteroscopy is fast becoming the first line treatment option for the majority of urinary tract stones. Ureteroscopy training can be performed in a variety of ways including simulation, hands on ureteroscopy courses and supervised operative experience. We report an "expert consensus view" from experienced endourological surgeons, on all aspects of basic ureteroscopic techniques, with a particular focus on avoiding and getting out of trouble while performing ureteroscopy. In this paper we provide a summary of treatment planning, positioning, cannulation of ureteric orifice, guidewire placement, rigid ureteroscopy and stone fragmentation. PMID- 26855798 TI - Priapism associated with novel psychoactive substance abuse. AB - Priapism is a time-dependent emergency, which can lead to marked adverse effects on erectile function. We present the case of a patient with bipolar disorder who consumed a novel psychoactive substance, as well as an illegal substitute for sildenafil citrate. History revealed erectile dysfunction most likely secondary to hyperprolactinaema. This case, therefore, raises the question of whether this patient demographic should be routinely screened for this complaint. PMID- 26855799 TI - Designer drugs and sexual dysfunction. PMID- 26855800 TI - AUTHOR'S REPLY. PMID- 26855606 TI - Search for flavour-changing neutral current top-quark decays to [Formula: see text] in [Formula: see text] collision data collected with the ATLAS detector at [Formula: see text] TeV. AB - A search for the flavour-changing neutral-current decay [Formula: see text] is presented. Data collected by the ATLAS detector during 2012 from proton-proton collisions at the Large Hadron Collider at a centre-of-mass energy of [Formula: see text] TeV, corresponding to an integrated luminosity of 20.3 fb[Formula: see text], are analysed. Top-quark pair-production events with one top quark decaying through the [Formula: see text] ([Formula: see text]) channel and the other through the dominant Standard Model mode [Formula: see text] are considered as signal. Only the decays of the Z boson to charged leptons and leptonic W boson decays are used. No evidence for a signal is found and an observed (expected) upper limit on the [Formula: see text] branching ratio of [Formula: see text] ([Formula: see text]) is set at the 95 % confidence level. PMID- 26855801 TI - Uropathogenic Escherichia coli virulence genes: invaluable approaches for designing DNA microarray probes. AB - INTRODUCTION: The pathotypes of uropathogenic Escherichia coli (UPEC) cause different types of urinary tract infections (UTIs). The presence of a wide range of virulence genes in UPEC enables us to design appropriate DNA microarray probes. These probes, which are used in DNA microarray technology, provide us with an accurate and rapid diagnosis and definitive treatment in association with UTIs caused by UPEC pathotypes. The main goal of this article is to introduce the UPEC virulence genes as invaluable approaches for designing DNA microarray probes. MATERIAL AND METHODS: Main search engines such as Google Scholar and databases like NCBI were searched to find and study several original pieces of literature, review articles, and DNA gene sequences. In parallel with in silico studies, the experiences of the authors were helpful for selecting appropriate sources and writing this review article. RESULTS: There is a significant variety of virulence genes among UPEC strains. The DNA sequences of virulence genes are fabulous patterns for designing microarray probes. The location of virulence genes and their sequence lengths influence the quality of probes. CONCLUSIONS: The use of selected virulence genes for designing microarray probes gives us a wide range of choices from which the best probe candidates can be chosen. DNA microarray technology provides us with an accurate, rapid, cost-effective, sensitive, and specific molecular diagnostic method which is facilitated by designing microarray probes. Via these tools, we are able to have an accurate diagnosis and a definitive treatment regarding UTIs caused by UPEC pathotypes. PMID- 26855802 TI - Repair of a vesico-vaginal fistula with amniotic membrane - Step 1 of the IDEAL recommendations of surgical innovation. AB - INTRODUCTION: Complex vesico-vaginal fistula (VVF) has a high recurrence rate and so the repair with graft tissues seems to be favorable. Amniotic membrane (AM) plays an increasing role as a scaffold for the repair of defect tissue due to its unique biological properties with regard to promoting wound healing. MATERIAL AND METHODS: An innovative surgical procedure for AM-assisted repair of a complex vesico-vaginal fistula as the Idea Stage following the IDEAL recommendations is presented. The development of amnion preparation and the involved surgical steps are described. RESULTS: We are able to report a successful repair of VVF by abdominal approach with an amniotic membrane graft. Good functional results, no adverse events and no graft rejection have been detected. CONCLUSIONS: Favorable results confirm the technical simplicity, safety and efficacy of this procedure. Following the IDEAL recommendations, consecutive animal experiments and a cohort study are in progress. PMID- 26855803 TI - Efficacy of holmium laser urethrotomy and intralesional injection of Santosh PGI tetra-inject (Triamcinolone, Mitomycin C, Hyaluronidase and N-acetyl cysteine) on the outcome of urethral strictures. AB - INTRODUCTION: To study the efficacy of holmium laser urethrotomy with intralesional injection of Santosh PGI tetra-inject (Triamcinolone, Mitomycin C, Hyaluronidase and N-acetyl cysteine) in the treatment of urethral strictures. MATERIAL AND METHODS: A total of 50 patients with symptomatic urethral stricture were evaluated by clinical history, physical examination, uroflowmetry and retrograde urethrogram preoperatively. All patients were treated with holmium laser urethrotomy, followed by injection of tetra-inject at the urethrotomy site. Tetra-inject was prepared by diluting acombination of 40 mg Triamcinolone, 2 mg Mitomycin, 3000 UHyaluronidase and 600 mg N-acetyl cysteine in 5-10 ml of saline, according to the stricture length. An indwelling 18 Fr silicone catheter was left in place for 7-10 days.All patients were followed-up for 6-18 months postoperatively by history, uroflowmetry, and if required, retrograde urethrogram and micturating urethrogram every 3 months. RESULTS: 41 (82%) patients had asuccessful outcome,whereas 9 (18%) had recurrences during a follow-up ranging from 6-18 months. In <1 cm length strictures, the success rate was 100%, while in 1-3 cm and >3 cm lengthsthe success rates were 81.2% and 66.7% respectively. This modality, thus, has an encouraging success rate, especially in those with short segment urethral strictures (<3 cm). CONCLUSIONS: Holmium laser urethrotomy with intralesional injection ofSantosh PGI tetra-inject (Triamcinolone, Mitomycin C, Hyaluronidase, N-acetyl cysteine) is a safe and effective minimally-invasive therapeutic modality for short segment urethral strictures. PMID- 26855804 TI - Role of laparoscopy in ureteropelvic junction obstruction with concomitant pathology: a case series study. AB - INTRODUCTION: Laparoscopic pyeloplasty is considered a standard treatment for ureteropelvic junction obstruction (UPJO). However, the presence of another pathology makes it a more challenging operation and guides the surgeon towards open conversion. In this study, we present our experience in difficult pyeloplasty cases managed by laparoscopy. MATERIAL AND METHODS: Six patients (4 females and 2 males) with an average age of 44 and a range of 27 to 60 years old, were diagnosed for UPJO. Three were on the left side and 3 on the right side. In addition to UPJO, 2 patients had renal stones, one patient had both renal ptosis and an umbilical hernia, 3 patients had a para-pelvic cyst, hepatomegaly and malrotated kidney, respectively. All patients had a preoperative ultrasound, CT or IVU, and a renal isotope scan. Laparoscopic pyeloplasty was performed according to the dismembered Anderson-Hynes technique with auxiliary maneuver, according to the pathology. RESULTS: All patients were treated successfully for UPJO and the concomitant pathologies, except hepatomegaly and malrotation. Mean operative time was 125 minutes and estimated blood loss was <50 ml. CONCLUSIONS: Laparoscopic pyeloplasty can be performed in difficult situations provided that the surgeon has enough experience with laparoscopy. PMID- 26855806 TI - SUPRAPUR((r)): Safe and convenient percutaneous suprapubic catheterisation in high-risk patients. AB - INTRODUCTION: Ultrasound-guided percutaneous placement of a suprapubic cystostomy is a common and generally safe procedure in everyday surgery. In case of adverse patient characteristics such as small bladder capacity or high body mass index, however, the procedure carries an increased risk of severe complications, including bowel perforation. The Suprapur((r)) cystostomy set is supposed to enable a safer procedure. The aim of our work was to evaluate the safety and ease of use of the Suprapur((r)) cystostomy set. MATERIAL AND METHODS: We prospectively evaluated the Suprapur((r)) set in high-risk patients, having either a small bladder capacity below 250 ml or a BMI above 30 kg/m(2). Complications and surgical outcome were monitored. In addition, patients' contentment and pain during the procedure was assessed with a visual analogue scale (VAS). Possible drawbacks and ease of use were evaluated by customized questionnaires for the operating physician. RESULTS: In total, 26 cystostomies were performed by 15 different physicians, 40% (n = 6) of whom were inexperienced first or second year residents. No complications occurred. Mild gross haematuria occurred in 11.5% (n = 4) of cases. Average VAS for pain during and two hours after the procedure was 2.1 (+/-1.2) and 0.3 (+/-0.5) respectively. In 91%, (n = 20) of the procedures, the physicians claimed to have felt safe using SUPRAPUR((r)) and more comfortable (82%, n = 18) than with a conventional cystostomy set. CONCLUSIONS: SUPRAPUR((r)) allows a safe and simple placement of a suprapubic cystostomy even in high-risk patients or in inexperienced hands. It might help to reduce the complications of a common and frequent surgical procedure. PMID- 26855805 TI - Experience of renal artery embolization in patients with blunt kidney trauma. AB - INTRODUCTION: The ren is considered as the most commonly damaged genitourinary organ. In general, blunt kidney traumas (BKT) are mild and can be managed conservatively. We aimed to analyze our own experiences of selective renal artery embolization (RAE) in BKT patients and compare obtained results with other reports. MATERIAL AND METHODS: We analyzed the medical and technical outcomes of RAE in 20 patients with grades II-IV blunt kidney traumas. Indications for RAE were blunt kidney trauma combined with a gross hematuria that could not be stopped conservatively. For evaluating the functioning of kidneys we used radioisotope renography. RESULTS: According to the American Association for the Surgery of Trauma classification, grade II blunt kidney injury was registered at 2 (10.0%) pts, grade III - at 11 (55.0%) pts and grade IV - at 7 (35.0%) pts. In all patients, the bleeding was stopped with the embolization procedure. 18 (90.0%) patients were treated in a single interventional session and 2 (10.0%) needed further intervention. Different complications were registered as 5 (25%) pts: two or more complications were often combined in each individual case. The function in damaged kidneys was preserved at the 3(rd) month after RAE sessions. CONCLUSIONS: RAE is an effective, minimally invasive treatment for blunt kidney injury that ensures the cessation of gross hematuria and kidney function preserving. PMID- 26855807 TI - Proton pump inhibitor prescription abuse and sepsis in cirrhosis. AB - Proton pump inhibitors (PPIs) represent one of the most extensively prescribed classes of drugs in general and in patients with liver cirrhosis. Many prescriptions are made without a clear adherence to standard indications. As a class of ordinarily well tolerated drug, PPIs are not free of side-effects and concerns have been raised about a possible role for PPIs in predisposing patients to an increased risk of bacterial infections and sepsis. As evidences of different power are accumulating on this topic, prospective studies are needed to reach a more universal agreement, but definitely more attention is needed by prescribers in being more adherent to the few recognized indications for the use of PPIs, particularly in patients with liver cirrhosis. Otherwise, doctors could run the risk of being accused of "abused" prescription. PMID- 26855811 TI - Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease. AB - There is currently no gold standard test for the diagnosis of inflammatory bowel disease (IBD). Physicians must rely on a number of diagnostic tools including clinical and endoscopic evaluation as well as histologic, serologic and radiologic assessment. The real difficulty for physicians in both primary and secondary care is differentiating between patients suffering from functional symptoms and those with true underlying IBD. Alongside this, there is always concern regarding the possibility of a missed, or delayed diagnosis of ulcerative colitis (UC) or Crohn's disease. Even once the diagnosis of IBD has been made, there is often uncertainty in distinguishing between cases of UC or Crohn's. As a consequence, in cases of incorrect diagnosis, optimal treatment and management may be adversely affected. Endoscopic evaluation can be uncomfortable and inconvenient for patients. It carries significant risks including perforation and in terms of monetary cost, is expensive. The use of biomarkers to help in the diagnosis and differentiation of IBD has been increasing over time. However, there is not yet one biomarker, which is sensitive of specific enough to be used alone in diagnosing IBD. Current serum testing includes C-reactive protein and erythrocyte sedimentation rate, which are cheap, reliable but non-specific and thus not ideal. Stool based testing such as faecal calprotectin is a much more specific tool and is currently in widespread clinical use. Non-invasive sampling is of the greatest clinical value and with the recent advances in metabolomics, genetics and proteomics, there are now more tools available to develop sensitive and specific biomarkers to diagnose and differentiate between IBD. Many of these new advances are only in early stages of development but show great promise for future clinical use. PMID- 26855810 TI - Hepatitis C virus: A time for decisions. Who should be treated and when? AB - Cirrhosis is the most important risk factor for hepatocellular carcinoma (HCC) regardless of the etiology of cirrhosis. Compared to individuals who are anti hepatitis C virus (HCV) seronegative, anti-HCV seropositive individuals have a greater mortality from both hepatic as well as nonhepatic disease processes. The aim of this paper is do describe the burden of HCV infection and consider treatment strategies to reduce HCV-related morbidity and mortality. The newly developed direct acting antiviral (DAA) therapies are associated with greater rates of drug compliance, fewer adverse effects, and appear not to be limited by the presence of a variety of factors that adversely affect the outcome of interferon-based therapies. Because of the cost of the current DAA, their use has been severely rationed by insurers as well as state and federal agencies to those with advanced fibrotic liver disease (Metavir fibrosis stage F3-F4). The rationale for such rationing is that many of those recognized as having the disease progress slowly over many years and will not develop advanced liver disease manifested as chronic hepatitis C, cirrhosis, and experience any of the multiple complications of liver disease to include HCC. This mitigation has a short sided view of the cost of treatment of hepatitis C related disease processes and ignores the long-term expenses of hepatitis C treatment consisting of the cost of treatment of hepatitis C, the management of cirrhosis with or without decompensation as well as the cost of treatment of HCC and liver transplantation. We believe that treatment should include all HCV infected patients including those with stage F0-F2 fibrosis with or without evidence of coexisting liver disease. Specifically, interferon (IFN)-free regimens with the current effective DAAs without liver staging requirements and including those without evidence of hepatic diseases but having recognized extrahepatic manifestations of HCV infection is projected to be the most cost-effective approach for treating HCV in all of its varied presentations. Early rather than later therapy of HCV infected individuals would be even more efficacious than waiting particularly if it includes all cases from F0-F4 hepatic disease. Timely therapy will reduce the number of individuals developing advanced liver disease, reduce the cost of treating these cases and more importantly, reduce the lifetime cost of treatment of those with any form of HCV related disease as well as HCV associated all - cause mortality. Importantly, HCV treatment regimens without any restrictions would result in a substantial reduction in health care expenditure and simultaneously reduce the number of infected individuals who are infecting others. PMID- 26855808 TI - Pharmacological- and non-pharmacological therapeutic approaches in inflammatory bowel disease in adults. AB - Inflammatory bowel diseases (IBDs) are a group of chronic inflammatory conditions mainly of the colon and small intestine. Crohn's disease (CD) and ulcerative colitis (UC) are the most frequent types of IBD. IBD is a complex disease which arises as a result of the interaction of environmental, genetic and immunological factors. It is increasingly thought that alterations of immunological reactions of the patients to their own enterable bacteria (microfilm) may contribute to inflammation. It is characterized by mucosal and sub mucosal inflammation, perpetuated by infiltration of activated leukocytes. CD may affect the whole gastrointestinal tract while UC only attacks the large intestine. The therapeutic goal is to achieve a steroid-free long lasting remission in both entities. UC has the possibility to be cured by a total colectomy, while CD never can be cured by any operation. A lifelong intake of drugs is mostly necessary and essential. Medical treatment of IBD has to be individualized to each patient and usually starts with anti-inflammatory drugs. The choice what kind of drugs and what route administered (oral, rectal, intravenous) depends on factors including the type, the localization, and severity of the patient's disease. IBD may require immune suppression to control symptoms such as prednisolone, thiopurines, calcineurin or sometimes folic acid inhibitors or biologics like TNF-alpha inhibitors or anti integrin antibodies. For both types of disease (CD, UC) the same drugs are available but they differ in their preference in efficacy between CD and UC as 5 aminosalicylic acid for UC or budesonide for ileocecal CD. As therapeutic alternative the main mediators of the disease, namely the activated pro inflammatory cytokine producing leukocytes can be selectively removed via two apheresis systems (Adacolumn and Cellsorba) in steroid-refractory or dependent cases. Extracorporeal photopheresis results in an increase of regulatory B cells, regulatory CD8(+) T cells and T-regs Type 1. Both types of apheresis were able to induce clinical remission and mucosal healing accompanied by tapering of steroids. PMID- 26855809 TI - Recent discoveries and emerging therapeutics in eosinophilic esophagitis. AB - Eosinophilic esophagitis (EoE) is an allergy-mediated disease culminating in severe eosinophilic inflammation and dysfunction of the esophagus. This chronic disorder of the esophagus causes significant morbidity, poor quality of life, and complications involving fibrosis and esophageal remodeling. Overlapping features between EoE and gastroesophageal reflux disease (GERD) pose great challenges to differentiating the two conditions, although the two disorders are not mutually exclusive. Recent findings suggest that the confounding condition proton pump inhibitor - responsive esophageal eosinophilia (PPI-REE) is likely a subset of EoE. Since PPIs have therapeutic properties that can benefit EoE, PPIs should be considered as a therapeutic option for EoE rather than a diagnostic screen to differentiate GERD, PPI-REE, and EoE. Other current treatments include dietary therapy, corticosteroids, and dilation. Immunomodulators and biologic agents might have therapeutic value, and larger trials are needed to assess efficacy and safety. Understanding the pathophysiology of EoE is critical to the development of novel therapeutics. PMID- 26855813 TI - Eosinophilic esophagitis: New insights in pathogenesis and therapy. AB - Eosinophilic esophagitis (EoE) is a clinico-pathological entity with esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus that may persist despite treatment with proton pump inhibitors. This eosinophilic infiltration is usually absent in the stomach, small intestine and colon, although there are a number of reports of patients with a multi-organ involvement. EoE is associated with abnormalities involving TH2-dependent immunity, with multiple environmental factors strongly contributing to disease expression. The layer of the esophagus affected by the eosinophilic infiltration causes the specific symptoms. Esophageal involvement results mostly in dysphagia for solids that can be severe enough to cause recurrent esophageal obstruction with typical endoscopic features suggesting esophageal remodeling and pathological changes of eosinophilic infiltration of the mucosa, sub-epithelial fibrosis and muscle hypertrophy. This disease is frequently associated with other allergic conditions such as allergic asthma, allergic dermatitis and eosinophilia. The treatment of patients with EoE depends on the severity of the symptoms and of the inflammatory process as well as to their response to a gradual step-up treatment. The first line of treatment consists of steroid containing local inhalers. If unresponsive they are then treated with oral steroids. Intravenous interleukin blockers seem to have a consistent positive therapeutic effect. PMID- 26855812 TI - Elderly patients and inflammatory bowel disease. AB - The incidence and prevalence of inflammatory bowel disease (IBD) is increasing globally. Coupled with an ageing population, the number of older patients with IBD is set to increase. The clinical features and therapeutic options in young and elderly patients are comparable but there are some significant differences. The wide differential diagnosis of IBD in elderly patients may result in a delay in diagnosis. The relative dearth of data specific to elderly IBD patients often resulting from their exclusion from pivotal clinical trials and the lack of consensus guidelines have made clinical decisions somewhat challenging. In addition, age specific concerns such as co-morbidity; loco-motor and cognitive function, poly-pharmacy and its consequences need to be taken into account. In applying modern treatment paradigms to the elderly, the clinician must consider the potential for more pronounced adverse effects in this vulnerable group and set appropriate boundaries maximising benefit and minimising harm. Meanwhile, clinicians need to make personalised decisions but as evidence based as possible in the holistic, considered and optimal management of IBD in elderly patients. In this review we will cover the clinical features and therapeutic options of IBD in the elderly; as well as addressing common questions and challenges posed by its management. PMID- 26855816 TI - Review of vedolizumab for the treatment of ulcerative colitis. AB - The review summarises the key data on the efficacy and the safety of vedolizumab in the management of ulcerative colitis. PMID- 26855814 TI - Diagnosis and management of functional symptoms in inflammatory bowel disease in remission. AB - Inflammatory bowel disease (IBD) patients in remission may suffer from gastrointestinal symptoms that resemble irritable bowel syndrome (IBS). Knowledge on this issue has increased considerably in the last decade, and it is our intention to review and summarize it in the present work. We describe a problematic that comprises physiopathological uncertainties, diagnostic difficulties, as IBS-like symptoms are very similar to those produced by an inflammatory flare, and the necessity of appropriate management of these patients, who, although in remission, have impaired quality of life. Ultimately, from almost a philosophical point of view, the presence of IBS-like symptoms in IBD patients in remission supposes a challenge to the traditional functional organic dichotomy, suggesting the need for a change of paradigm. PMID- 26855815 TI - Clinical applications, limitations and future role of transient elastography in the management of liver disease. AB - Transient elastography (TE) is a reliable tool for the non-invasive assessment of liver fibrosis in routine clinical practice. TE is currently approved for use in Europe, Asia and the United States. The widespread adoption of this technology is certain to increase the use of TE worldwide. Although TE has been well validated in chronic viral hepatitis, its clinical role in other liver diseases remains less clear. The advent of new treatment for chronic hepatitis C and emerging prevalence of non-alcoholic steatohepatitis raises new questions on the role of TE in current clinical practice. This review aims to examine the clinical applications, limitations and future role of TE in current clinical practice in light of the changing epidemiology of liver diseases and new clinical management paradigms. In current clinical practice, TE is the most accurate non-invasive method for diagnosis of liver cirrhosis. TE is useful to rule out fibrosis and cirrhosis but does not have sufficient accuracy to discern between various stages of fibrosis. The clinical role of TE has evolved from cross-sectional point-in time assessment of fibrosis and cirrhosis to the more relevant role of prediction of vital clinical end-points. This provides clinicians with the ability to modify treatment strategies based on the information provided by TE. TE has evolved over the past decade to become an essential tool to assist the clinician in the management of chronic liver disease. PMID- 26855818 TI - Helicobacter pylori and its reservoirs: A correlation with the gastric infection. AB - Helicobacter pylori (H. pylori) has long been found to cause gastric diseases such as gastritis, gastric ulcers and gastric cancer. The transmission medium of this bacterium has yet to be determined, though several studies have speculated that the oral cavity is a reservoir for H. pylori. Others have also reported that the oral cavity may be a source of both transmission and gastric reinfection; however, such results are controversial. We reviewed the literature and selected studies that report an association among H. pylori detections in the oral cavity (dental plaque, saliva, tongue, tonsil tissue, root canals, oral mucosa) in humans and in animals, as well as in the human stomach. The oral cavity may be considered the main reservoir for H. pylori. There are a correlations between H. pylori infection in the oral cavity and periodontal disease, oral tissue inflammation, H. pylori transmission, and gastric reinfection. We believe that the mouth is a reservoir and that it plays a crucial role in both H. pylori transmission and gastric infection. PMID- 26855820 TI - Under-diagnosing and under-treating iron deficiency in hospitalized patients with gastrointestinal bleeding. AB - AIM: To determine whether patients hospitalized with gastrointestinal (GI) blood loss anemia are being checked and treated for iron deficiency. METHODS: Retrospective chart review was conducted for all patients admitted to a single tertiary care hospital between 11/1/2011 and 1/31/2012 for any type of GI bleeding. The primary endpoint was the percentage of patients who had their iron studies checked during a hospitalization for GI blood loss anemia. Secondary outcomes included percentage of anemic GI bleeders who had adequate documentation of anemia and iron deficiency, and those who were treated for their iron deficiency. Then we tried to identify possible predictors of checking iron studies in an attempt to understand the thought process that physicians go through when managing these patients. Iron deficiency was defined as Iron saturation less than 15% or ferritin level less than 45 MUg/L. Anemia was defined as hemoglobin level less than 13 g/dL for males and 12 g/dL for females. RESULTS: Three hundred and seven GI bleeders were hospitalized during the study period, and 282 of those (91.9%) had anemia during their hospital stay. Ninety-five patients (30.9%) had iron studies performed during hospitalization, and 45 of those (47.4%) were actually found to be iron deficient. Only 29 of those 45 iron deficient patients were discharged home on iron supplements. Of the 282 patients that had anemia during hospitalization, 50 (17.7%) had no documentation of the anemia in their hospital chart. Of the 45 patients that had lab proven iron deficiency anemia (IDA), only 22 (48.5%) had documentation of IDA in at least one note in their chart. Predictors of checking iron studies in anemic GI bleeders were lower mean corpuscular volume, documentation of anemia, having fecal occult blood testing, not having hematemesis or past history of GI bleeding. There were no significant differences between the teaching and non-teaching services in any patient characteristics or outcomes. CONCLUSION: Iron deficiency is under diagnosed, under-recognized even when iron studies were checked, and under treated in hospitalized patients with GI bleeding. PMID- 26855819 TI - Dendritic cell-based vaccine for pancreatic cancer in Japan. AB - "Vaccell" is a dendritic cell (DC)-based cancer vaccine which has been established in Japan. The DCs play central roles in deciding the direction of host immune reactions as well as antigen presentation. We have demonstrated that DCs treated with a streptococcal immune adjuvant OK-432, produce interleukin-12, induce Th1-dominant state, and elicit anti-tumor effects, more powerful than those treated with the known DC-maturating factors. We therefore decided to mature DCs by the OK-432 for making an effective DC vaccine, Vaccell. The 255 patients with inoperable pancreatic cancer who received standard chemotherapy combined with DC vaccines, were analyzed retrospectively. Survival time of the patients with positive delayed type hypersensitivity (DTH) skin reaction was significantly prolonged as compared with that of the patients with negative DTH. The findings strongly suggest that there may be "Responders" for the DC vaccine in advanced pancreatic cancer patients. We next conducted a small-scale prospective clinical study. In this trial, we pulsed HLA class II-restricted WT1 peptide (WT1-II) in addition to HLA class I-restricted peptide (WT1-I) into the DCs. Survival of the patients received WT1-I and -II pulsed DC vaccine was significantly extended as compared to that of the patients received DCs pulsed with WT1-I or WT1-II alone. Furthermore, WT1-specific DTH positive patients showed significantly improved the overall survival as well as progression-free survival as compared to the DTH negative patients. The activation of antigen specific immune responses by DC vaccine in combination with standard chemotherapy may be associated with a good clinical outcome in advanced pancreatic cancer. We are now planning a pivotal study of the Vaccell in appropriate protocols in Japan. PMID- 26855817 TI - Influence of environmental factors in the development of inflammatory bowel diseases. AB - Idiopathic inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial diseases that are manifested after disruption of a genetic predisposed individual and its intestinal microflora through an environmental stimulus. Urbanization and industrialization are associated with IBD. Epidemiological data, clinical observations and family/immigrants studies indicate the significance of environmental influence in the development of IBD. Some environmental factors have a different effect on the subtypes of IBD. Smoking and appendectomy is negatively associated with UC, but they are aggravating factors for CD. A westernized high fat diet, full of refined carbohydrates is strongly associated with the development of IBD, contrary to a high in fruit, vegetables and polyunsaturated fatty acid-3 diet that is protective against these diseases. High intake of nonsteroidal antiinflammatory drug and oral contraceptive pills as well as the inadequacy of vitamin D leads to an increased risk for IBD and a more malignant course of disease. Moreover, other factors such as air pollution, psychological factors, sleep disturbances and exercise influence the development and the course of IBD. Epigenetic mechanism like DNA methylation, histone modification and altered expression of miRNAS could explain the connection between genes and environmental factors in triggering the development of IBD. PMID- 26855821 TI - Effect of electrical stimulation of the lower esophageal sphincter in gastroesophageal reflux disease patients refractory to proton pump inhibitors. AB - AIM: To evaluate the efficacy of lower esophageal sphincter (LES)-electrical stimulation therapy (EST) in a subgroup of patients that reported only partial response to proton pump inhibitors (PPIs) therapy, compared to a group of patient with complete response. METHODS: Bipolar stitch electrodes were laparoscopically placed in the LES and connected to an implantable pulse generator (EndoStim BV, the Hague, the Netherlands), placed subcutaneously in the anterior abdominal wall. Stimulation at 20 Hz, 215 MUsec, 3-8 mAmp in 30 min sessions was delivered starting on day 1 post-implant. Patients were evaluated using gastroesophageal reflux disease (GERD)-HRQL, symptom diaries; esophageal pH and esophageal manometry before and up to 24 mo after therapy and results were compared between partial and complete responders. RESULTS: Twenty-three patients with GERD on LES EST were enrolled and received continuous per-protocol stimulation through 12 mo and 21 patients completed 24 mo of therapy. Of the 23 patients, 16 (8 male, mean age 52.1 +/- 12 years) had incomplete response to PPIs prior to LES-EST, while 7 patients (5 male, mean age 52.7 +/- 4.7) had complete response to PPIs. In the sub-group with incomplete response to PPIs, median (IQR) composite GERD-HRQL score improved significantly from 9.5 (9.0-10.0) at baseline on-PPI and 24.0 (20.8-26.3) at baseline off-PPI to 2.5 (0.0-4.0) at 12-mo and 0.0 (0.0-2.5) at 24 mo follow-up (P < 0.05 compared to on-and off-PPI at baseline). Median (IQR) % 24 h esophageal pH < 4.0 at baseline in this sub-group improved significantly from 9.8% (7.8-11.5) at baseline to 3.0% (1.9-6.3) at 12 mo (P < 0.001) and 4.6% (2.0 5.8) at 24 mo follow-up (P < 0.01). At their 24-mo follow-up, 9/11 patients in this sub-group were completely free of PPI use. These results were comparable to the sub-group that reported complete response to PPI therapy at baseline. No unanticipated implantation or stimulation-related adverse events, or any untoward sensation due to stimulation were reported in either group and LES-EST was safely tolerated by both groups. CONCLUSION: LES-EST is safe and effective in controlling symptoms and esophageal acid exposure in GERD patients with incomplete response to PPIs. These results were comparable to those observed PPI responders. PMID- 26855822 TI - Therapeutic effect of melatonin on pediatric functional dyspepsia: A pilot study. AB - AIM: To study the effectiveness of melatonin vs placebo in children with functional dyspepsia (FD). METHODS: The study was conducted as a double blind, randomized, placebo controlled crossover trial. Subjects were aged 8-17 years and diagnosed with FD based on Rome III criteria. All subjects had failed to respond to 4 wk of acid suppression. Subjects receive a continuous two weeks of placebo and a continuous two weeks of melatonin in an order blinded to the participant and the study team. A Global Clinical Score was obtained to assess changes in abdominal pain. Pain was self-reported to be worse (grade 1), no change (grade 2), moderate improvement (grade 3), good (grade 4; minimal pain and not interfering with daily activities), or excellent (grade 5; no pain), respectively. A positive clinical response was defined as a grade 3 or greater response. Subjects wore an actigraph to assess sleep during a one week baseline period and during each treatment period. Subjects' sleep latency and total sleep time were recorded throughout the duration of the study. RESULTS: Fourteen subjects were enrolled and 12 completed the study. One withdrew prior to starting both melatonin and placebo and the other before starting melatonin. A positive clinical response (grade 3-5) was achieved in 42% of subjects on melatonin vs 50% of subjects on placebo (NS). Effect size was calculated and revealed a Cohen's D of 0.343 which demonstrates a medium effect favoring placebo. A grade 4 or grade 5 response was seen in 4 patients on melatonin and 5 patients on placebo. Baseline sleep parameters were in the healthy range with the longest sleep latency being just over 20 min (mean 7.46 +/- 8.53 min) and the shortest sleep duration just over 7 h (mean 10.09 +/- 2.72 h). The mean latency did not differ between periods of treatment with melatonin as compared to placebo (4.48 +/- 6.45 min vs 3.58 +/- 4.24 min; NS). The mean sleep duration did not differ between periods of treatment with melatonin as compared to placebo (9.90 +/- 3.53 h vs 9.41 +/- 2.70 h; NS). CONCLUSION: Melatonin does not appear to have efficacy in relieving pain in unselected pediatric FD. Future studies should consider FD subtypes, pathophysiologic mechanisms, and baseline sleep disturbances. PMID- 26855823 TI - Economic evaluations in gastroenterology in Brazil: A systematic review. AB - AIM: To systematically review economic evaluations in gastroenterology, relating to Brazil, published between 1980 and 2013. METHODS: We selected full and partial economic evaluations from among those retrieved by searching the following databases: MEDLINE (PubMed); Excerpta Medica; the Latin American and Caribbean Health Sciences Literature database; the Scientific Electronic Library Online; the database of the Centre for Reviews and Dissemination; the National Health Service (NHS) Economic Evaluation Database; the NHS Health Technology Assessment database; the Health Economics database of the Brazilian Virtual Library of Health; Scopus; Web of Science; and the Brazilian Network for the Evaluation of Health Technologies. Two researchers, working independently, selected the studies and extracted the data. RESULTS: We identified 535 health economic evaluations relating to Brazil and published in the 1980-2013 period. Of those 535 articles, only 40 dealt with gastroenterology. Full and partial economic evaluations respectively accounted for 23 (57.5%) and 17 (42.5%) of the 40 studies included. Among the 23 full economic evaluations, there were 11 cost-utility analyses, seven cost-effectiveness analyses, four cost-consequence analyses, and one cost minimization analysis. Of the 40 studies, 25 (62.5%) evaluated medications; 7 (17.5%) evaluated procedures; and 3 (7.5%) evaluated equipment. Most (55%) of the studies were related to viral hepatitis, and most (63.4%) were published after 2010. Other topics included gastrointestinal cancer, liver transplantation, digestive diseases and hernias. Over the 33-year period examined, the number of such economic evaluations relating to Brazil, especially of those evaluating medications for the treatment of hepatitis, increased considerably. CONCLUSION: Further studies are needed in order to ensure that expenditures on health care in Brazil are made as fairly and efficiently as possible. PMID- 26855824 TI - A Prototype for a Hybrid System to Support Systematic Review Teams: A Case Study of Organ Transplantation. AB - We describe a prototype for a hybrid system designed to reduce the number of citations needed to re-screen (NNRS) by systematic reviewers, where citations include titles, abstracts, and metadata. The system obviates the need for screening the entire set of citations a second time, which is typically done to control human error. The reference set is based on a complex review about organ transplantation (N=10,796 citations). Data were split into 50% training and test sets, randomly stratified for percentage eligible citations. The system consists of a rule-based module and a machine-learning (ML) module. The former substantially reduces the number of negative citations passed to the ML module and improves imbalance. Relative to the baseline, the system reduces classification error (5.6% vs 2.9%) thereby reducing NNRS by 47.3% (300 vs 158). We discuss the implications of de-emphasizing sensitivity (recall) in favor of specificity and negative predictive value to reduce screening burden. PMID- 26855825 TI - Biophysical EPR Studies Applied to Membrane Proteins. AB - Membrane proteins are very important in controlling bioenergetics, functional activity, and initializing signal pathways in a wide variety of complicated biological systems. They also represent approximately 50% of the potential drug targets. EPR spectroscopy is a very popular and powerful biophysical tool that is used to study the structural and dynamic properties of membrane proteins. In this article, a basic overview of the most commonly used EPR techniques and examples of recent applications to answer pertinent structural and dynamic related questions on membrane protein systems will be presented. PMID- 26855827 TI - A MS-lesion pattern discrimination plot based on geostatistics. AB - INTRODUCTION: A geostatistical approach to characterize MS-lesion patterns based on their geometrical properties is presented. METHODS: A dataset of 259 binary MS lesion masks in MNI space was subjected to directional variography. A model function was fit to express the observed spatial variability in x, y, z directions by the geostatistical parameters Range and Sill. RESULTS: Parameters Range and Sill correlate with MS-lesion pattern surface complexity and total lesion volume. A scatter plot of ln(Range) versus ln(Sill), classified by pattern anisotropy, enables a consistent and clearly arranged presentation of MS-lesion patterns based on geometry: the so-called MS-Lesion Pattern Discrimination Plot. CONCLUSIONS: The geostatistical approach and the graphical representation of results are considered efficient exploratory data analysis tools for cross sectional, follow-up, and medication impact analysis. PMID- 26855826 TI - High-gamma power changes after cognitive intervention: preliminary results from twenty-one senior adult subjects. AB - INTRODUCTION: Brain-imaging techniques have begun to be popular in evaluating the effectiveness of cognitive intervention training. Although gamma activities are rarely used as an index of training effects, they have several characteristics that suggest their potential suitability for this purpose. This pilot study examined whether cognitive training in elderly people affected the high-gamma activity associated with attentional processing and whether high-gamma power changes were related to changes in behavioral performance. METHODS: We analyzed (MEG) magnetoencephalography data obtained from 35 healthy elderly subjects (60 75 years old) who had participated in our previous intervention study in which the subjects were randomly assigned to one of the three types of intervention groups: Group V trained in a vehicle with a newly developed onboard cognitive training program, Group P trained with a similar program but on a personal computer, and Group C was trained to solve a crossword puzzle as an active control group. High-gamma (52-100 Hz) activity during a three-stimulus visual oddball task was measured before and after training. As a result of exclusion in the MEG data analysis stage, the final sample consisted of five subjects in Group V, nine subjects in Group P, and seven subjects in Group C. RESULTS: Results showed that high-gamma activities were differently altered between groups after cognitive intervention. In particular, members of Group V, who showed significant improvements in cognitive function after training, exhibited increased high-gamma power in the left middle frontal gyrus during top-down anticipatory target processing. High-gamma power changes in this region were also associated with changes in behavioral performance. CONCLUSIONS: Our preliminary results suggest the usefulness of high-gamma activities as an index of the effectiveness of cognitive training in elderly subjects. PMID- 26855829 TI - Distal Radius Volar Rim Fracture Fixation Using DePuy-Synthes Volar Rim Plate. AB - Background To assess the results of distal radius fractures with the involvement of the volar rim fixed with the DePuy-Synthes Volar Rim Plate. Case Description We searched for the patients with volar rim fracture and/or volar rim fractures as part of a complex fracture fixed with a volar rim plate. Ten patients met the inclusion criteria: three patients with type 23B3, six patients with type 23C, and one patient with very distal type 23A. The mean follow-up was 14 months (range: 2-26). Fractures healed in all patients. Of the three patients with isolated volar rim fractures (type 23B3), two patients had no detectable deficits in motion. These patients had an average Gartland and Werley score of 9 (range: 2 14). Of the other seven patients (six with type 23C and one with type 23A fracture), three patients healed with full range of motion and four had some deficits in range of motion. Two patients had excellent results, three had good results, and two had fair results using the Gartland and Werley categorical rating. One patient healed with a shortened radius and ulnar impingement requiring a second surgery for ulnar head resection arthroplasty. Literature Review Results after nonoperative treatment of volar rim fractures are not satisfactory and often require subsequent corrective osteotomy. Satisfactory outcomes are achieved when the fragments are well reduced and secured regardless of the device type. Clinical Relevance Volar rim plates give an adequate buttress of the volar radius distal to volar projection of the lunate facet and do not interfere with wrist mobility. Furthermore, the dorsal fragments can be fixed securely through the volar approach eliminating the need for a secondary posterior incision. However, patients should be informed of the potential problems and the need to remove the plate if symptoms develop. PMID- 26855828 TI - Fully automated open-source lesion mapping of T2-FLAIR images with FSL correlates with clinical disability in MS. AB - BACKGROUND: T2 Lesion Volume (T2LV) has been an important biomarker for multiple sclerosis (MS). Current methods available to quantify lesions from MR images generally require manual adjustments or multiple images with different contrasts. Further, implementations are often not easily or openly accessible. OBJECTIVE: We created a fully unsupervised, single T2 FLAIR image T2LV quantification package based on the popular open-source imaging toolkit FSL. METHODS: By scripting various processing tools in FSL, we developed an image processing pipeline that distinguishes normal brain tissue from CSF and lesions. We validated our method by hierarchical multiple regression (HMR) with a preliminary study to see if our T2LVs correlate with clinical disability measures in MS when controlled for other variables. RESULTS: Pearson correlations between T2LV and Expanded Disability Status Scale (EDSS: r = 0.344, P = 0.013), Six-Minute Walk (6MW: r = -0.513, P = 0.000), Timed 25-Foot Walk (T25FW: r = -0.438, P = .000), and Symbol Digit Modalities Test (SDMT: r = -0.499, P = 0.000) were all significant. Partial correlations controlling for age were significant between T2LV and 6MW (r = 0.433, P = 0.002), T25FW (r = -0.392, P = 0.004), and SDMT (r = -0.450, P = 0.001). In HMR, T2LV explained significant additional variance in 6MW (R(2) change = 0.082, P = 0.020), after controlling for confounding variables such as age, white matter volume (WMV), and gray matter volume (GMV). CONCLUSION: Our T2LV quantification software produces T2LVs from a single FLAIR image that correlate with physical disability in MS and is freely available as open-source software. PMID- 26855831 TI - Prevent Collapse and Salvage Failures of the Volar Rim of the Distal Radius. AB - Background Articular fractures of the distal radius may include a small fragment from the volar margin of the lunate fossa: volar marginal fragments (VMFs); these fragments are prone to loss of fixation and avascular necrosis, and often result in wrist subluxation. We present our experience managing acute and delayed VMFs. The first is treated using a hook plate extension to a volar locking plate and the latter using a volar opening wedge osteotomy to redistribute loads on the remaining articular surface. Materials and Methods We retrospectively reviewed the records of all patients treated at our facility with a hook plate extension for a VMF and for patients treated with a volar opening wedge osteotomy. Medical charts were examined for complications and functional results. Technique A hook plate extension was used to fix the VMF when plate buttressing was insufficient. For patients who presented a collapsed and reabsorbed VMF, a volar opening wedge osteotomy was used to reorient the articular surface, restoring joint stability. Results The hook plate extension was successful in managing 19 of the 21 acute VMFs. The volar opening wedge osteotomy provided concentric reduction and improved pain and motion in all treated patients. Conclusion We demonstrated that hook plate fixation of the VMF is an effective means of fixing the acute VMF and that a volar opening wedge osteotomy can be used to salvage a distal radius fracture with a collapsed VMF. PMID- 26855830 TI - Fixation Options for the Volar Lunate Facet Fracture: Thinking Outside the Box. AB - Background Fractures of the distal radius with small volar ulnar marginal fracture fragments are difficult to stabilize with standard volar locking plates. The purpose of this study is to describe alternative techniques available to stabilize these injuries. Materials and Methods Five patients were identified retrospectively with unstable volar lunate facet fracture fragments treated with supplemental fixation techniques. The demographic data, pre- and postoperative radiographic parameters, and early outcomes data were analyzed. The AO classification, preoperative and final postoperative ulnar variance, articular step-off, volar tilt, radial inclination, and teardrop angle were measured. The lunate subsidence and length of the volar cortex available for fixation were measured from the initial injury films. Description of Technique Lunate facet fixation was based on the morphology of the fragment, and stabilization was achieved with headless compression screws in three patients, a tension band wire construct in one, and two cortical screws in another. Results Five patients with a mean age of 58 years (range: 41-82) were included. There were two AO C3.2 and three B3.3 fractures. Preoperative radiographic measurements including radial inclination, tilt, and ulnar variance all improved after surgery and were maintained within normal limits at 3-month follow-up. There was no change in the teardrop angle at final follow-up (70-64 degrees; p = 0.14). None of the patients had loss of fixation or volar carpal subluxation. The mean visual analog scale pain score at 3 months was 1 (range: 0-2). Conclusions The morphology of volar lunate facet fracture fragments is variable, and fixation must be customized to the particular pattern. Small fragments may preclude the use of plates and screws for fixation. These fractures can be managed successfully with tension band wire constructs and headless screws. These low-profile implants may decrease the risk of tendon irritation that might accompany distally placed plates. PMID- 26855832 TI - Fragment-Specific Fixation for Fractures of the Distal Radius. AB - This article summarizes the management of distal fractures utilizing Acumed fragment-specific family of plates. No single plate option can address every fracture pattern of the distal radius. These fragment-specific plates are usually adjuncts to allow the surgeon to expand the armamentarium in the management of complex volar and dorsal comminuted distal radius fracture patterns. PMID- 26855833 TI - The Effect of Displaced Dorsal Rim Fragment in a Distal Radius Fracture. AB - Background In intra-articular fracture of distal radius, the intra-articular fragments can be divided into some specific fragments. In particular, the poor outcomes have been well documented for reduction loss of the volar lunate facet, but the effect of a displaced dorsal rim fracture has rarely been addressed. Materials and Methods The records of 26 patients with dorsal rim fragment displaced by more than 2 mm after volar locking plate (VLP) fixation for a dorsally displaced distal radius fracture (DRF) treated from March 2006 to March 2009 were retrospectively reviewed. Clinical assessments including grip strengths, wrist range of motions, and Disabilities of Arm, Shoulder, and Hand (DASH) scores were performed at 12 months postoperatively. Widths of the distal ends of dorsal rims were determined by preoperative computed tomography (CT). Dorsal rim fragment displacements were measured in immediate postoperative plain lateral radiographs. Radial inclination, volar tilt, and ulnar variance were measured on immediate postoperative wrist radiographs. Arthritic changes of radiocarpal joints were graded using radiographs obtained at 12 months postoperatively. Description of Technique DRFs were fixed using a VLP in the usual manner. Although DRF displacement was noticed after plate fixation, no further procedure was performed. The sizes of articular portions of dorsal rim fragments were measured arthroscopically in 5 of the 26 patients at the time of plate fixation. Results At 12 months postoperatively, mean grip strength, wrist flexion arc, and mean wrist extension arc were 86 +/- 13, 87 +/- 11, and 91 +/- 10%, respectively, of contralateral sides. Mean forearm supination and pronation were 96 +/- 8 and 99 +/- 5%, respectively, of contralateral sides. Mean DASH score was 11 +/- 10 points. Preoperatively, mean width of the distal end of dorsal rim fragments and mean displacements of dorsal rim fragments were 2.0 +/- 0.6 and 3.0 +/- 0.9 mm, respectively. Mean width of the articular portions of dorsal rim fragment by arthroscopic examination was 1.0 +/- 0.4 mm. Mean radial inclination was 21 +/- 4.8 degrees, mean volar angulation was 4.8 +/- 3.9 degrees, and mean ulnar variance was 0.6 +/- 1.8 mm at immediate postoperatively. Two patients showed grade I arthritic changes at 12 months postoperatively. Conclusions The articular portions of dorsal rim fragments measured arthroscopically were smaller than determined by CT. Furthermore, the study shows that displaced dorsal rim fragments in dorsally displaced DRFs treated by VLP do not adversely affect wrist clinical outcomes. PMID- 26855834 TI - Ultrasound Imaging Improves Identification of Prominent Hardware in the Surgical Treatment of Distal Radius Fractures: A Cadaveric and Prospective Clinical Study. AB - Background Volarly applied locking plates are one of several current treatment options for displaced fractures of the distal radius. Presently, surgeons use intraoperative depth gauges and fluoroscopy to select and confirm proper screw length. The contour of the dorsal cortex beneath the extensor compartments along with fracture comminution may limit the accuracy of screw length selection. Question/Purpose To evaluate the accuracy of ultrasound (US) and fluoroscopy in the detection of dorsally prominent screws placed during volar plating of experimentally created distal radius fractures and extend this prospectively into the clinical setting. Patients and Methods Distal radius fractures were experimentally induced in fresh cadaveric arms. The fractures were then internally fixated with volar locking plates utilizing fluoroscopic imaging. US imaging of the dorsal surface of the radius was then performed followed by dorsal dissection and direct caliper measurements to quantitate screw tips as recessed, flush, or protruding from the dorsal cortex. A small, prospective clinical study was also conducted to validate the clinical usefulness of using US to provide additional information regarding screw tip prominence. Results Our study demonstrated that US was able to detect dorsally prominent screw tips not visible on fluoroscopy. Cadaveric dissection showed a higher statistical correlation between US imaging and actual prominence than between fluoroscopy and actual prominence. Conclusions US examination after volar plate fixation of comminuted distal radius fractures may detect dorsal screw tip prominence when screw lengths are selected to engage the dorsal cortex. Level of Evidence IV. PMID- 26855835 TI - Dorsal Tear of Triangular Fibrocartilage Complex: Clinical Features and Treatment. AB - Background Several different triangular fibrocartilage complex (TFCC) tear patterns have been classified through the use of wrist arthroscopy. A tear of the dorsal aspect of the TFCC has been previously reported, but it is not included in Palmer original classification. Our purpose was to describe this type of tear pattern along with the clinical presentation. Methods An isolated dorsal TFCC tear was encountered in seven wrists of six patients (three men and three women; average age was 31 years). All patients were evaluated by physical exam, X-ray, plain axial computed tomography with pronation, neutral and supination position, magnetic resonance imaging (MRI) with coronal, sagittal, and axial section and arthroscopy. Results The clinical findings varied and included the following: tenderness at the dorsoulnar aspect of the wrist was positive in all wrists, fovea sign was positive in five wrists, and tenderness at the dorsal aspect of the distal radioulnar joint was present in one wrist. Pain with forearm rotation was positive in all wrists. The ulnar head ballottement test induced pain in all wrists, whereas dorsal instability of the ulnar head was present in one wrist with this test. The ulnocarpal stress test was positive in five wrists. Axial and sagittal images on MRI revealed the dorsal tear in five wrists. All wrists were treated with an arthroscopic capsular repair. The final functional outcome at an average follow-up of 16.1 months was four excellent and one good wrist according to the modified Mayo wrist score. Conclusions The aim of this article is to describe our experiences with tears involving the dorsal aspect of the TFCC, which may be misdiagnosed if the surgeon is not cognizant of this injury. Type of study/level of evidence Diagnostic/level IV. PMID- 26855836 TI - The Effect of Scaphoid Fracture Site on Scaphoid Instability Patterns. AB - Background Scaphoid fractures are common carpal fractures that are often misdiagnosed as wrist sprains and may go on to nonunion. The location of the fracture site may influence the stability of scaphoid nonunions. Purpose To determine whether the stability of a scaphoid nonunion depends upon the fracture's location, we tested the hypothesis that a simulated fracture distal to the apex of the scaphoid dorsal ridge will have greater interfragmentary motion than proximal. Methods Eleven cadaver wrists were moved through three wrist motions using a wrist simulator. In six wrists, a fracture was created distal to the scaphoid apex, and in five a fracture was created proximal to the apex. Sensors attached to the distal and proximal parts of each scaphoid measured the interfragmentary motion during wrist motion. Results In those wrists in which the scaphoid was sectioned distal to the apex, the distal fragment became significantly more unstable relative to the proximal fragment. It flexed, ulnarly deviated, and pronated. These motion changes were less when the scaphoid was sectioned proximally. Discussion Scaphoid fractures distal to the scaphoid apex will have greater interfragmentary motion. The mobility of the fragments at the fracture site is possibly a more important contributory factor of nonunion in scaphoid waist fractures than for proximal scaphoid fractures. Clinical Relevance Understanding the effect that the location of a scaphoid fracture has on the potential for nonunion may influence the modalities of treatment and follow-up. PMID- 26855837 TI - Intra-articular Fractures of the Sigmoid Notch of the Distal Radius: Analysis of Progression to Distal Radial Ulnar Joint Arthritis and Impact on Upper Extremity Function in Surgically Treated Fractures. AB - Background Studies have established an increased risk of radiocarpal joint posttraumatic arthritis in patients with displaced intra-articular fractures of the distal radius, although this phenomenon has yet to be evaluated in the distal radioulnar joint (DRUJ). Purpose We hypothesized that patients with displaced intra-articular fractures of the sigmoid notch would have a higher prevalence of DRUJ arthritis and greater upper extremity dysfunction after operative treatment of distal radius fractures compared with fractures without sigmoid notch involvement. We also hypothesized that the degree of sigmoid notch incongruity would be correlated with the grade of DRUJ arthritis and the severity of upper extremity dysfunction. Patients and Methods A retrospective review was conducted on surgically treated patients with distal radius fractures with pre- and/or postoperative computed tomography (CT) scans. Patients were divided into groups based on presence or absence of fracture extension into the sigmoid notch. Within the sigmoid notch group, postoperative CT scans were used to measure sigmoid notch fracture step-off and diastasis (mm), as well as volar or dorsal DRUJ subluxation (%). Patients were administered Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaires and radiographs were obtained to grade DRUJ arthritis using the Kellgren-Lawrence (KL) radiographic criteria. Results Thirty three patients were included (19 with sigmoid notch involvement and 14 without) with an average radiographic follow-up of 6.3 years (range: 3.5-10.1 years). DASH scores were available for all patients, and radiographic follow-up was available in 24 patients (73%). A trend toward higher grade of DRUJ arthritis and poorer average DASH was found in those with sigmoid notch involvement, but was not statistically different. In the sigmoid notch group there were poorer DASH scores in patients with coronal step-off > 1.0-mm (p < 0.05). There were no significant correlations between sigmoid notch step-off, diastasis or DRUJ subluxation and either KL grade of arthritis or DASH scores. Conclusion Fractures involving the sigmoid notch did not appear to have a greater prevalence of DRUJ posttraumatic arthritis in operatively treated patients at greater than 6 years of follow-up. Postoperative sigmoid notch step-off, diastasis or DRUJ subluxation had a minimal effect on upper extremity function, but fractures with a coronal step-off of > 1.0-mm exhibited higher levels of upper extremity dysfunction. Level of Evidence Prognostic, Level III-Case control. PMID- 26855838 TI - ScaphoLunate Axis Method. AB - Background Treating chronic scapholunate ligament injuries without the presence of arthritis remains an unsolved clinical problem facing wrist surgeons. This article highlights a technique for reconstructing the scapholunate ligament using novel fixation, the ScaphoLunate Axis Method (SLAM). Materials and Methods In a preliminary review of the early experience of this technique, 13 patients were evaluated following scapholunate ligament reconstruction utilizing the SLAM technique. Description of Techinque The scapholunate interval is reconstructed utilizing a palmaris longus autograft passed between the scaphoid and lunate along the axis of rotation in the sagittal plane. It is secured in the lunate using a graft anchor and in the scaphoid utilizing an interference screw. The remaining graft is passed dorsally to reconstruct the dorsal scapholunate ligament. Results At an average follow-up of 11 months, the mean postoperative scapholunate gap was 2.1 mm. The mean postoperative scapholunate angle was 59 degrees. The mean postoperative wrist flexion and extension was 45 and 56 degrees, respectively. The mean grip strength was 24.9 kg, or 62% of the contralateral side. The mean pain score (VAS) was 1.7. There was 1 failure with recurrence of the pathologic scapholunate gap and the onset of pain. Conclusion While chronic scapholunate ligament instability remains an unsolved problem facing wrist surgeons, newer techniques are directed toward restoring the normal relationships of the scaphoid and lunate in both the coronal and sagittal planes. The SLAM technique has demonstrated promise in preliminary clinical studies. PMID- 26855839 TI - Epidermal Inclusion Cyst after Carpal Tunnel Release: A Case Report. AB - Background Carpal tunnel release is one of most commonly performed procedures in upper extremity surgery, with low complication rates. Case Description We report a case of epidermal inclusion cyst that occurred in a 44-year old man after carpal tunnel release. The epidermal inclusion cyst formed beneath the previous operation scar and induced recurrent carpal tunnel syndrome. Symptoms resolved completely after excision of the cyst. Literature Review Epidermal inclusion cysts are the third most common type of hand tumors. Although repeated minor trauma is the most frequent cause, surgical procedures can induce an epidermal inclusion cyst. One case report of epidermal inclusion cyst after carpal tunnel release was found in literature. Etiology, treatment, and prevention methods are reviewed. Clinical Relevance We hope this case report alerts physicians to the possibility of development of epidermal inclusion cyst after carpal tunnel release and the importance of basic surgical skills, such as gentle handling of a surgical wound, profuse saline irrigation, and careful wound closure with precise approximation of skin edges. PMID- 26855840 TI - Scaphoid Proximal Pole Fracture Following Headless Screw Fixation. AB - Background Headless screw fixation of scaphoid fractures and nonunions yields predictably excellent outcomes with a relatively low complication profile. However, intramedullary implants affect the load to failure and stress distribution within bone and may be implicated in subsequent fracture. Case Description We describe a posttraumatic fracture pattern of the scaphoid proximal pole originating at the previous headless screw insertion site in three young male patients with healed scaphoid nonunions. Each fracture was remarkably similar in shape and size, comprised the volar proximal pole, and was contiguous with the screw entry point. Treatment was challenging but successful in all cases. Literature Review Previous reports have posited that stress-raisers secondary to screw orientation may be implicated in subsequent peri-implant fracture of the femoral neck. Repeat scaphoid fracture after screw fixation has also been reported. However, the shape and locality of secondary fracture have not been described, nor has the potential role of screw fixation in the production of distinct fracture patterns. Clinical Relevance Hand surgeons must be aware of this difficult complication that may follow antegrade headless screw fixation of scaphoid fracture nonunion, and of available treatment strategies. PMID- 26855841 TI - Acute Monoarthritis of the Wrist Joint: Tuberculosis or Not? AB - Background Extrapulmonary tuberculosis (EPTB) is known to have many and varied presentations. However, isolated involvement of bone with tubercular infection is uncommon. The clinical features of such infections are known to mimic chronic pyogenic osteomyelitis, Brodie abscess, or tumors, but not acute monoarthritis. Case Description We describe here an unusual case of tuberculous osteomyelitis that mimicked features of acute monoarthritis of the wrist joint. Literature Review Extraspinal tuberculous osteomyelitis is rare and comprises only about 2 to 3% of all cases of osteoarticular tuberculosis, with the hip and knee joints being the most commonly involved. An extensive literature review did not show any published report of tuberculous osteomyelitis presenting as acute monoarthritis of the wrist joint. Clinical Relevance This case underlines the importance of making EPTB an important differential diagnosis even in cases with clinical features that are completely inconsistent with tubercular infections. PMID- 26855842 TI - Volar Central Portal in Wrist Arthroscopy. AB - Background Nowadays, the wrist is not limited to a dorsal visualization; the joint can be thought of as a "box," which can be visualized from almost every perspective. The purpose of this study was to describe a new volar central portal for the wrist, following three principles: a single incision that allows access to both the radiocarpal and midcarpal joints, centered on the lunate, with the volar structures at risk protected not only by retractors, but also by tendons. Description of Technique The incision begins in the distal wrist crease and extended 1.5 cm proximally up to the proximal wrist crease, following the axis of the third intermetacarpal space. The flexor superficialis tendons are identified and retracted toward the radial side. Next, the fourth and fifth flexor digitorum profundus tendons are retracted toward the ulnar side, while the third and second tendons are retracted toward the radial side. The volar central midcarpal portal is performed under direct vision just over the anterior horn of the lunate through the Poirier space. The volar central radiocarpal portal is created under the lunate through the interval between the ulnocarpal ligaments and the short radioulnar ligament. Methods An anatomical study was performed on 14 cadaver specimens. Two data were recorded: iatrogenic injuries of the structures at risk and the distances to the structures at risk. Results The median (interquartile range [IQR]) distances from the volar central radiocarpal portal to the median nerve, palmar cutaneous branch of the median nerve, and ulnar neurovascular bundle were 10.5 (7.8-15.0), 18.5 (15.8-20.3), and 7.0 (5.0-10.5) mm, respectively. The median (IQR) distances from the volar central midcarpal portal to the median nerve, palmar cutaneous branch of the median nerve, and ulnar neurovascular bundle were 7.0 (4.8-10.3), 16.0 (14.8-19.0), and 4.5 (3.8-9.0) mm, respectively. No iatrogenic injuries were observed. Conclusion The volar central portal is reproducible and safe. The risk of iatrogenic injury is low. The capsule is pierced through one of its thinner portions, and both the radiocarpal and midcarpal joints can be inspected through one single incision. PMID- 26855843 TI - Three-Year Efficacy and Safety of a Silicone Oil-Filled Foldable-Capsular Vitreous-Body in Three Cases of Severe Retinal Detachment. AB - PURPOSE: We previously designed a novel foldable capsular vitreous body (FCVB) to treat severe retinal detachment and evaluated its performance in a 1-year follow up study. The purpose of this study was to determine the efficacy and safety of a silicone oil (SO)-filled FCVB in a 3-year follow-up. METHODS: Standard three-port pars plana vitrectomy was performed, and the FCVB was triple folded and implanted in the vitreous cavity of three eyes. The SO then was injected into the capsule to support the retina. The eyes were examined using Goldmann applanation tonometry, fundus photography, optical coherence tomography (OCT), noncontact specular microscopy, and ultrasound biomicroscopy over a 3-year implantation period. RESULTS: At the 3-year follow-up, retinal reattachment was achieved in all three cases, with steady intraocular pressure. The visual acuity showed slight fluctuations, and it was slightly increased compared to baseline. Optical coherence tomography revealed decreased retinal thickness and an altered retinal structure in the implanted eyes compared to the control eyes. No keratopathy, glaucoma, SO leakage, SO emulsification, or other apparent complications occurred during the observation period. CONCLUSION: The SO-filled FCVB was effective and safe as a vitreous substitute in three eyes over a 3-year observation period. TRANSLATIONAL RELEVANCE: Silicone oil emulsification is a severe complication after retinal detachment surgery. On the basis of animal experiments, we investigated a new strategy and product, the FCVB, to overcome this complication. In this pilot study, FCVB limited SO emulsification and migration. This study could lay the foundation for a further multicenter clinical trial. PMID- 26855844 TI - In vivo subcellular resolution optical imaging in the lung reveals early metastatic proliferation and motility. AB - To better understand breast cancer metastatic cell seeding, we have employed multiphoton microscopy and a vacuum stabilized window which eliminates the need for complex registration software, video rate microscopy or specialized gating electronics to observe the initial steps of tumor cell seeding within the living, breathing lung. We observe that upon arrival to the lung, tumor cells are found exclusively in capillary vessels, completely fill their volume and display an initial high level of protrusive activity that dramatically reduces over time. Further, we observe a concomitant increase in positional stability during this same period. We employ several techniques accessible to most imaging labs for optimizing signal to noise and resolution which enable us to report the first direct observation, with subcellular resolution, of the arrival, proliferation, and motility of metastatic tumor cells within the lung. PMID- 26855846 TI - Attitudes Toward Breast Cancer Genetic Testing in Five Special Population Groups. AB - PURPOSE: This study examined interest in and attitudes toward genetic testing in 5 different population groups. METHODS: The survey included African American, Asian American, Latina, Native American, and Appalachian women with varying familial histories of breast cancer. A total of 49 women were interviewed in person. Descriptive and nonparametric statistical techniques were used to assess ethnic group differences. RESULTS: Overall, interest in testing was high. All groups endorsed more benefits than risks. There were group differences regarding endorsement of specific benefits and risks: testing to "follow doctor recommendations" (p=0.017), "concern for effects on family" (p=0.044), "distrust of modern medicine" (p=0.036), "cost" (p=0.025), and "concerns about communication of results to others" (p=0.032). There was a significant inverse relationship between interest and genetic testing cost (p<0.050), with the exception of Latinas, who showed the highest level of interest regardless of increasing cost. CONCLUSION: Cost may be an important barrier to obtaining genetic testing services, and participants would benefit by genetic counseling that incorporates the unique cultural values and beliefs of each group to create an individualized, culturally competent program. Further research about attitudes toward genetic testing is needed among Asian Americans, Native Americans, and Appalachians for whom data are severely lacking. Future study of the different Latina perceptions toward genetic testing are encouraged. PMID- 26855845 TI - Fall Risk is Not Black and White. AB - OBJECTIVE: To determine whether previously reported racial differences in fall rates between White and Black/African American is explained by differences in health status and neighborhood characteristics. DESIGN: Prospective cohort. SETTING: Community. PARTICIPANTS: The study included 550 White and 116 Black older adults in the Greater Boston area (mean age: 78 years; 36% men) who were English-speaking, able to walk across a room, and without severe cognitive impairment. MEASUREMENTS: Falls were prospectively reported using monthly fall calendars. The location of each fall and fall-related injuries were asked during telephone interviews. At baseline, we assessed risk factors for falls, including sociodemographic characteristics, physiologic risk factors, physical activity, and community-level characteristics. RESULTS: Over the mean follow-up of 1,048 days, 1,539 falls occurred (incidence: 806/1,000 person-years). Whites were more likely than Blacks to experience any falls (867 versus 504 falls per 1,000 person years; RR [95% CI]: 1.77 [1.33, 2.36]), outdoor falls (418 versus 178 falls per 1,000 person-years; 1.78 [1.08, 2.92]), indoor falls (434 versus 320 falls per 1,000 person-years; 1.44 [1.02, 2.05]), and injurious falls (367 versus 205 falls per 1,000 person-years; 1.79 [1.30, 2.46]). With exception of injurious falls, higher fall rates in Whites than Blacks were substantially attenuated with adjustment for risk factors and community-level characteristics: any fall (1.24 [0.81, 1.89]), outdoor fall (1.57 [0.86, 2.88]), indoor fall (1.08 [0.64, 1.81]), and injurious fall (1.77 [1.14, 2.74]). CONCLUSION: Our findings suggest that the racial differences in fall rates may be largely due to confounding by individual level and community-level characteristics. PMID- 26855847 TI - Association between Depression and Aggression in Rural Women. AB - Rural women represent approximately 20% of women living in the United States, yet research on the specific mental health needs of rural women is limited. Given the well-recognized gender-linked difference in depression rates, its correlated depressive symptoms in women still need much investigation. While emerging notions of depression in men embrace potential symptoms related to irritability and aggression, less research has focused on the potential role of aggression in depressed women. This connection may be particularly relevant for rural women who face unique mental health stressors in comparison to their urban counterparts. The purpose of this study was to examine if aggression is linked to depression for rural women in order to identify potential unique symptomatology and presentation for rural women. As part of a larger initiative, a sample of 54 participants was recruited from the patient population at a Federally Qualified Health Center (FQHC) in rural southeast Georgia to participate in a quantitative survey. The survey explored demographics, depression, and aggressive behavior. Mean total score of aggression in depressed women was significantly higher than non-depressed women (p < 0.001), and within the entire sample depression scores were significantly related linearly to aggression, with aggression explaining 16% of the variance found in depression scores (beta = .399, r2 = .159, p = 0.003). This study suggests that aggressive behavior may be linked to depression for rural women, and underscores the need for future research investigating if depression presents differently for rural women. PMID- 26855848 TI - A 10.6mm3 Fully-Integrated, Wireless Sensor Node with 8GHz UWB Transmitter. AB - This paper presents a complete, autonomous, wireless temperature sensor, fully encapsulated in a 10.6mm3 volume. The sensor includes solar energy harvesting with an integrated 2 MUAh battery, optical receiver for programming, microcontroller and memory, 8GHz UWB transmitter, and miniaturized custom antennas with a wireless range of 7 meters. Full, stand-alone operation was demonstrated for the first time for a system of this size and functionality. PMID- 26855849 TI - A 99nW 70.4kHz Resistive Frequency Locking On-Chip Oscillator with 27.4ppm/ degrees C Temperature Stability. AB - We present a low power on-chip oscillator for system-on-chip designs. The oscillator introduces a resistive frequency locking loop topology where the equivalent resistance of a switched-capacitor is matched to a temperature compensated resistor. The approach eliminates the traditional comparator from the oscillation loop, which consumes significant power and limits temperature stability in conventional relaxation oscillators. The oscillator is fabricated in 0.18MUm CMOS and exhibits 27.4ppm/ degrees C and <7ppm long-term stability while consuming 99.4nW at 70.4 kHz. PMID- 26855850 TI - A 120nW 8b Sub-ranging SAR ADC with Signal-Dependent Charge Recycling for Biomedical Applications. AB - We present an 8-bit sub-ranging SAR ADC designed for bursty signals having long time periods with small code spread. A modified capacitive-DAC (CDAC) saves previous sample's MSB voltage and reuses it throughout subsequent conversions. This prevents unnecessary switching of large MSB capacitors as well as conversion cycles, reducing energy consumed in the comparator and digital logic and yielding total energy savings of 2.6*. In 0.18MUm CMOS, the ADC consumes 120nW at 0.6V and 100kS/s with 46.9dB SNDR. PMID- 26855851 TI - Hand Transplantation Versus Hand Prosthetics: Pros and Cons. AB - Composite tissue transplantation and new developments in the field of prosthetics have opened new frontiers in the restoration of function among upper limb amputees. It is now possible to restore hand function in affected patients; however, the indications, advantages, and limitations for either hand transplantation or prosthetic fitting must be carefully considered depending on the level and extent of the limb loss. Hand transplantation allows comprehensive hand function to be restored, yet composite tissue transplantation comes with disadvantages, making this method a controversial topic in the hand surgical community. Alternatively, prosthetic limb replacement represents the standard of care for upper limb amputees, but results in the known limitations of function, sensation, and usage. The indication for hand transplantation or prosthetic fitting strongly depends on the level of amputation, as well as on the extent (unilateral/bilateral) of the amputation. In this review, we discuss the advantages and disadvantages of hand transplantation and prosthetic replacement for upper limb amputees in general, as well as in regard to the different levels of amputation. PMID- 26855853 TI - Isolation and characterization of eight polymorphic microsatellites for the spotted spiny lobster, Panulirus guttatus. AB - Microsatellite sequences were isolated from enriched genomic libraries of the spotted spiny lobster, Panulirus guttatus using 454 pyrosequencing. Twenty-nine previously developed polymerase chain reaction primer pairs of Panulirus argus microsatellite loci were also tested for cross-species amplification in Panulirus guttatus. In total, eight consistently amplifying, and polymorphic loci were characterized for 57 individuals collected in the Florida Keys and Bermuda. The number of alleles per locus ranged from 8 to 20 and observed heterozygosities ranged from 0.409 to 0.958. Significant deviations from Hardy-Weinberg equilibrium were found in one locus from Florida and three loci from Bermuda. Quality control testing indicated that all loci were easy to score, highly polymorphic and showed no evidence of linkage disequilibrium. Null alleles were detected in three loci with moderate frequencies ranging from (20% to 22%). These eight microsatellites provide novel molecular markers for future conservation genetics research of P. guttatus. PMID- 26855852 TI - Real-life experience with personally familiar faces enhances discrimination based on global information. AB - Despite the agreement that experience with faces leads to more efficient processing, the underlying mechanisms remain largely unknown. Building on empirical evidence from unfamiliar face processing in healthy populations and neuropsychological patients, the present experiment tested the hypothesis that personal familiarity is associated with superior discrimination when identity information is derived based on global, as opposed to local facial information. Diagnosticity and availability of local and global information was manipulated through varied physical similarity and spatial resolution of morph faces created from personally familiar or unfamiliar faces. We found that discrimination of subtle changes between highly similar morph faces was unaffected by familiarity. Contrariwise, relatively more pronounced physical (i.e., identity) differences were more efficiently discriminated for personally familiar faces, indicating more efficient processing of global, as opposed to local facial information through real-life experience. PMID- 26855854 TI - Lemmas induce dormancy but help the seed of Leymus chinensis to resist drought and salinity conditions in Northeast China. AB - Leymus chinensis is a dominant grass in the Songnen grassland of Northern China. The lower germination caused by the presence of lemmas has proved to be an obstacle for the use of the seeds of this plant by humans. However, it is still unknown if the lemmas have other ecological roles such as resisting drought and saline conditions. Three experiments were designed to investigate the ecological roles of the lemmas in Leymus chinensis seeds. The results showed that lemmas significantly improved the amount of water uptake and slowed down the dehydration rate of the seeds under dry conditions. Likewise, the lemmas induced seed dormancy, and removal of the lemmas improved the germination at all temperatures. Although germination percentage of the seeds without lemmas were higher than that of seeds with lemmas under salinity stress, the recovery and total percentage were significantly lower than the seeds with lemmas, especially at 400 mM stress. These results suggest that the lemmas play a vital function in water uptake, dehydration and salt tolerance during the germination stage of the seeds as a response to adverse environmental conditions. Although lemmas showed a dormancy effect, if we want to plant this species in salinity soil in Northeast China, the approach of removing the lemmas by artificial means and improving the seed germination percentage is not feasible. PMID- 26855855 TI - Reproducibility of SNV-calling in multiple sequencing runs from single tumors. AB - We examined 55 technical sequencing replicates of Glioblastoma multiforme (GBM) tumors from The Cancer Genome Atlas (TCGA) to ascertain the degree of repeatability in calling single-nucleotide variants (SNVs). We used the same mutation-calling pipeline on all pairs of samples, and we measured the extent of the overlap between two replicates; that is, how many specific point mutations were found in both replicates. We further tested whether additional filtering increased or decreased the size of the overlap. We found that about half of the putative mutations identified in one sequencing run of a given sample were also identified in the second, and that this percentage remained steady throughout orders of magnitude of variation in the total number of mutations identified (from 23 to 10,966). We further found that using filtering after SNV-calling removed the overlap completely. We concluded that there is variation in the frequency of mutations in GBMs, and that while some filtering approaches preferentially removed putative mutations found in only one replicate, others removed a large fraction of putative mutations found in both. PMID- 26855856 TI - Structural strength of cancellous specimens from bovine femur under cyclic compression. AB - The incidence of osteoporotic fractures was estimated as nine million worldwide in 2000, with particular occurrence at the proximity of joints rich in cancellous bone. Although most of these fractures spontaneously heal, some fractures progressively collapse during the early post-fracture period. Prediction of bone fragility during progressive collapse following initial fracture is clinically important. However, the mechanism of collapse, especially the gradual loss of the height in the cancellous bone region, is not clearly proved. The strength of cancellous bone after yield stress is difficult to predict since structural and mechanical strength cannot be determined a priori. The purpose of this study was to identify whether the baseline structure and volume of cancellous bone contributed to the change in cancellous bone strength under cyclic loading. A total of fifteen cubic cancellous bone specimens were obtained from two 2-year old bovines and divided into three groups by collection regions: femoral head, neck, and proximal metaphysis. Structural indices of each 5-mm cubic specimen were determined using micro-computed tomography. Specimens were then subjected to five cycles of uniaxial compressive loading at 0.05 mm/min with initial 20 N loading, 0.3 mm displacement, and then unloading to 0.2 mm with 0.1 mm displacement for five successive cycles. Elastic modulus and yield stress of cancellous bone decreased exponentially during five loading cycles. The decrease ratio of yield stress from baseline to fifth cycle was strongly correlated with bone volume fraction (BV/TV, r = 0.96, p < 0.01) and structural model index (SMI, r = - 0.81, p < 0.01). The decrease ratio of elastic modulus from baseline to fifth cycle was also correlated with BV/TV (r = 0.80, p < 0.01) and SMI (r = - 0.78, p < 0.01). These data indicate that structural deterioration of cancellous bone is associated with bone strength after yield stress. This study suggests that baseline cancellous bone structure estimated from adjacent non-fractured bone contributes to the cancellous bone strength during collapse. PMID- 26855857 TI - Experimental modulation of external microbiome affects nestmate recognition in harvester ants (Pogonomyrmex barbatus). AB - Social insects use odors as cues for a variety of behavioral responses, including nestmate recognition. Past research on nestmate recognition indicates cuticular hydrocarbons are important nestmate discriminators for social insects, but other factors are likely to contribute to colony-specific odors. Here we experimentally tested whether external microbes contribute to nestmate recognition in red harvester ants (Pogonomyrmex barbatus). We changed the external microbiome of ants through topical application of either antibiotics or microbial cultures. We then observed behavior of nestmates when treated ants were returned to the nest. Ants whose external microbiome was augmented with microbial cultures were much more likely to be rejected than controls, but ants treated with antibiotics were not. This result is consistent with the possibility that external microbes are used for nestmate recognition. PMID- 26855858 TI - Auditory ERP response to successive stimuli in infancy. AB - Background. Auditory Event-Related Potentials (ERPs) are useful for understanding early auditory development among infants, as it allows the collection of a relatively large amount of data in a short time. So far, studies that have investigated development in auditory ERPs in infancy have mainly used single sounds as stimuli. Yet in real life, infants must decode successive rather than single acoustic events. In the present study, we tested 4-, 8-, and 12-month-old infants' auditory ERPs to musical melodies comprising three piano notes, and examined ERPs to each individual note in the melody. Methods. Infants were presented with 360 repetitions of a three-note melody while EEG was recorded from 128 channels on the scalp through a Geodesic Sensor Net. For each infant, both latency and amplitude of auditory components P1 and N2 were measured from averaged ERPs for each individual note. Results. Analysis was restricted to response collected at frontal central site. For all three notes, there was an overall reduction in latency for both P1 and N2 over age. For P1, latency reduction was significant from 4 to 8 months, but not from 8 to 12 months. N2 latency, on the other hand, decreased significantly from 4 to 8 to 12 months. With regard to amplitude, no significant change was found for either P1 or N2. Nevertheless, the waveforms of the three age groups were qualitatively different: for the 4-month-olds, the P1-N2 deflection was attenuated for the second and the third notes; for the 8-month-olds, such attenuation was observed only for the middle note; for the 12-month-olds, the P1 and N2 peaks show relatively equivalent amplitude and peak width across all three notes. Conclusion. Our findings indicate that the infant brain is able to register successive acoustic events in a stream, and ERPs become better time-locked to each composite event over age. Younger infants may have difficulties in responding to late occurring events in a stream, and the onset response to the late events may overlap with the incomplete response to preceding events. PMID- 26855860 TI - Phylogenetic and morphologic evidence confirm the presence of a new montane cloud forest associated bird species in Mexico, the Mountain Elaenia (Elaenia frantzii; Aves: Passeriformes: Tyrannidae). AB - Here we provide evidence to support an extension of the recognized distributional range of the Mountain Elaenia (Elaenia frantzii) to include southern Mexico. We collected two specimens in breeding condition in northwestern Sierra Norte de Chiapas, Mexico. Morphologic and genetic evidence support their identity as Elaenia frantzii. We compared environmental parameters of records across the entire geographic range of the species to those at the northern Chiapas survey site and found no climatic differences among localities. PMID- 26855859 TI - The feasibility and radiological features of sacral alar iliac fixation in an adult population: a 3D imaging study. AB - BACKGROUND: Surgical treatments for adult spinal deformities often include pelvic fixation, and the feasibility of sacral-2 alar iliac (S2AI) screw fixation has been shown previously. However, sometimes S2AI screw fixation cannot be applied due to the presence of an osteolytic lesion or trauma or because the biomechanical properties of only an S2AI screw is insufficient. Therefore, we questioned the feasibility of using sacral AI screws in other segments and determined whether S3AI and S4AI screws have the potential to be used for sacral fractures. The aim of this study was to investigate the feasibility and radiological features of sacral AI fixation in S1-S4 in an adult population using 3D imaging techniques. METHODS: Computed tomography (CT) scans were taken of 45 patients and were imported into Mimics (Version 10.01, Materialise, Belgium) software to reconstruct the 3D digital images. Next, a cylinder (radius of 3.5 mm) was drawn to imitate the screw trajectory of a S1-4 AI screw, and every imitated screw in each segment was adjusted to a maximum upward and downward angle to acquire the feasible region. The parameters of the S1-4AI screw trajectories were measured. RESULTS: Sacral AI screws could be successfully imitated using 3D digital imaging. The S4AI screw trajectory could be obtained in 19 of 45 patient images (42.2%), while the feasibility rates of S1AI, S2AI, and S3AI screw fixation were 100%, 100%, and 91.1% (41/45), respectively. The feasible regions of S1AI, S2AI, and S3AI screw trajectories were wide enough, while the adjustable angle of S4AI screws was very small. CONCLUSION: It is feasible to place S1-2AI screws in the entire adult population and S3-4AI screws in some of the adult population. Furthermore, our study suggested that 3D digital images are suitable to study the feasibility of new screw fixation. PMID- 26855861 TI - A method for histopathological study of the multifocal nature of spinal cord lesions in murine experimental autoimmune encephalomyelitis. AB - Experimental autoimmune encephalomyelitis (EAE) is a well-established mouse model for multiple sclerosis and is characterized by infiltration of mononuclear cells and demyelination within the central nervous system along with the clinical symptoms of paralysis. EAE is a multifocal and random disease, which sometimes makes histopathologic analysis of lesions difficult as it may not be possible to predict where lesions will occur, especially when evaluating cross sections of spinal cord. Consequently, lesions may be easily missed due to limited sampling in traditional approaches. To evaluate the entire length of the spinal cord while maintaining anatomic integrity, we have developed a method to section the cord within the decalcified spinal column, which allows for the study of the multifocal nature of this disease and also minimizes handling artifact. HE and Luxol fast blue staining of these spinal cord sections revealed a paucity of lesions in some areas, while others showed marked inflammation and demyelination. The percentage of spinal cord affected by EAE was evaluated at four separate areas of longitudinally sectioned cord and it varied greatly within each animal. Immunohistochemical staining of in situ spinal cords which had undergone decalcification was successful for key immuno-markers used in EAE research including CD3 for T cells, B220 for B cells and F4/80 for murine macrophages. This method will allow investigators to look at the entire spinal cord on a single slide and evaluate the spinal cord with and without classic EAE lesions. PMID- 26855862 TI - Immunohistochemistry for the detection of neural and inflammatory cells in equine brain tissue. AB - Phenotypic characterization of cellular responses in equine infectious encephalitides has had limited description of both peripheral and resident cell populations in central nervous system (CNS) tissues due to limited species specific reagents that react with formalin-fixed, paraffin embedded tissue (FFPE). This study identified a set of antibodies for investigating the immunopathology of infectious CNS diseases in horses. Multiple commercially available staining reagents and antibodies derived from antigens of various species for manual immunohistochemistry (IHC) were screened. Several techniques and reagents for heat-induced antigen retrieval, non-specific protein blocking, endogenous peroxidase blocking, and visualization-detection systems were tested during IHC protocol development. Boiling of slides in a low pH, citrate-based buffer solution in a double-boiler system was most consistent for epitope retrieval. Pressure-cooking, microwaving, high pH buffers, and proteinase K solutions often resulted in tissue disruption or no reactivity. Optimal blocking reagents and concentrations of each working antibody were determined. Ultimately, a set of monoclonal (mAb) and polyclonal antibodies (pAb) were identified for CD3(+) (pAb A0452, Dako) T-lymphocytes, CD79alphacy(+) B-lymphocytes (mAb HM57, Dako), macrophages (mAb MAC387, Leica), NF-H(+) neurons (mAb NAP4, EnCor Biotechnology), microglia/macrophage (pAb Iba-1, Wako), and GFAP(+) astrocytes (mAb 5C10, EnCor Biotechnology). In paraffin embedded tissues, mAbs and pAbs derived from human and swine antigens were very successful at binding equine tissue targets. Individual, optimized protocols are provided for each positively reactive antibody for analyzing equine neuroinflammatory disease histopathology. PMID- 26855863 TI - The effect of habitual and experimental antiperspirant and deodorant product use on the armpit microbiome. AB - An ever expanding body of research investigates the human microbiome in general and the skin microbiome in particular. Microbiomes vary greatly from individual to individual. Understanding the factors that account for this variation, however, has proven challenging, with many studies able to account statistically for just a small proportion of the inter-individual variation in the abundance, species richness or composition of bacteria. The human armpit has long been noted to host a high biomass bacterial community, and recent studies have highlighted substantial inter-individual variation in armpit bacteria, even relative to variation among individuals for other body habitats. One obvious potential explanation for this variation has to do with the use of personal hygiene products, particularly deodorants and antiperspirants. Here we experimentally manipulate product use to examine the abundance, species richness, and composition of bacterial communities that recolonize the armpits of people with different product use habits. In doing so, we find that when deodorant and antiperspirant use were stopped, culturable bacterial density increased and approached that found on individuals who regularly do not use any product. In addition, when antiperspirants were subsequently applied, bacterial density dramatically declined. These culture-based results are in line with sequence based comparisons of the effects of long-term product use on bacterial species richness and composition. Sequence-based analyses suggested that individuals who habitually use antiperspirant tended to have a greater richness of bacterial OTUs in their armpits than those who use deodorant. In addition, individuals who used antiperspirants or deodorants long-term, but who stopped using product for two or more days as part of this study, had armpit communities dominated by Staphylococcaceae, whereas those of individuals in our study who habitually used no products were dominated by Corynebacterium. Collectively these results suggest a strong effect of product use on the bacterial composition of armpits. Although stopping the use of deodorant and antiperspirant similarly favors presence of Staphylococcaceae over Corynebacterium, their differential modes of action exert strikingly different effects on the richness of other bacteria living in armpit communities. PMID- 26855864 TI - Physiological response of the cold-water coral Desmophyllum dianthus to thermal stress and ocean acidification. AB - Rising temperatures and ocean acidification driven by anthropogenic carbon emissions threaten both tropical and temperate corals. However, the synergistic effect of these stressors on coral physiology is still poorly understood, in particular for cold-water corals. This study assessed changes in key physiological parameters (calcification, respiration and ammonium excretion) of the widespread cold-water coral Desmophyllum dianthus maintained for ~8 months at two temperatures (ambient 12 degrees C and elevated 15 degrees C) and two pCO2 conditions (ambient 390 ppm and elevated 750 ppm). At ambient temperatures no change in instantaneous calcification, respiration or ammonium excretion rates was observed at either pCO2 levels. Conversely, elevated temperature (15 degrees C) significantly reduced calcification rates, and combined elevated temperature and pCO2 significantly reduced respiration rates. Changes in the ratio of respired oxygen to excreted nitrogen (O:N), which provides information on the main sources of energy being metabolized, indicated a shift from mixed use of protein and carbohydrate/lipid as metabolic substrates under control conditions, to less efficient protein-dominated catabolism under both stressors. Overall, this study shows that the physiology of D. dianthus is more sensitive to thermal than pCO2 stress, and that the predicted combination of rising temperatures and ocean acidification in the coming decades may severely impact this cold-water coral species. PMID- 26855866 TI - New insights on Prestosuchus chiniquensis Huene, 1942 (Pseudosuchia, Loricata) based on new specimens from the "Tree Sanga" Outcrop, Chiniqua Region, Rio Grande do Sul, Brazil. AB - The 'rauisuchians' are a group of Triassic pseudosuchian archosaurs that displayed a near global distribution. Their problematic taxonomic resolution comes from the fact that most taxa are represented only by a few and/or mostly incomplete specimens. In the last few decades, renewed interest in early archosaur evolution has helped to clarify some of these problems, but further studies on the taxonomic and paleobiological aspects are still needed. In the present work, we describe new material attributed to the 'rauisuchian' taxon Prestosuchus chiniquensis, of the Dinodontosaurus Assemblage Zone, Middle Triassic (Ladinian) of the Santa Maria Supersequence of southern Brazil, based on a comparative osteologic analysis. Additionally, we present well supported evidence that these represent juvenile forms, due to differences in osteological features (i.e., a subnarial fenestra) that when compared to previously described specimens can be attributed to ontogeny and indicate variation within a single taxon of a problematic but important osteological structure in the study of 'rauisuchians.' PMID- 26855865 TI - Sustained attention in skilled and novice martial arts athletes: a study of event related potentials and current sources. AB - Background. Research on sports has revealed that behavioral responses and event related brain potentials (ERP) are better in expert than in novice athletes for sport-related tasks. Focused attention is essential for optimal athletic performance across different sports but mainly in combat disciplines. During combat, long periods of focused attention (i.e., sustained attention) are required for a good performance. Few investigations have reported effects of expertise on brain electrical activity and its neural generators during sport unrelated attention tasks. The aim of the present study was to assess the effect of expertise (i.e., skilled and novice martial arts athletes) analyzing the ERP during a sustained attention task (Continuous Performance Task; CPT) and the cortical three-dimensional distribution of current density, using the sLORETA technique. Methods. CPT consisted in an oddball-type paradigm presentation of five stimuli (different pointing arrows) where only one of them (an arrow pointing up right) required a motor response (i.e., target). CPT was administered to skilled and novice martial arts athletes while EEG were recorded. Amplitude ERP data from target and non-target stimuli were compared between groups. Subsequently, current source analysis for each ERP component was performed on each subject. sLORETA images were compared by condition and group using Statistical Non-Parametric Mapping analysis. Results. Skilled athletes showed significant amplitude differences between target and non-target conditions in early ERP components (P100 and P200) as opposed to the novice group; however, skilled athletes showed no significant effect of condition in N200 but novices did show a significant effect. Current source analysis showed greater differences in activations in skilled compared with novice athletes between conditions in the frontal (mainly in the Superior Frontal Gyrus and Medial Frontal Gyrus) and limbic (mainly in the Anterior Cingulate Gyrus) lobes. Discussion. These results are supported by previous findings regarding activation of neural structures that underlie sustained attention. Our findings may indicate a better-controlled attention in skilled athletes, which suggests that expertise can improve effectiveness in allocation of attentional resources during the first stages of cognitive processing during combat. PMID- 26855867 TI - Age-related changes of dental pulp tissue after experimental tooth movement in rats. AB - It is generally accepted that the effect of orthodontic tooth movement on the dental pulp in adolescents is reversible and that it has no long-lasting effect on pulpal physiology. However, it is not clear yet if the same conclusion is also valid for adult subjects. Thus, in two groups of rats, aged 6 and 40 weeks respectively, 3 molars at one side of the maxilla were moved together in a mesial direction with a standardized orthodontic appliance delivering a force of 10 cN. The contralateral side served as a control. Parasagittal histological sections were prepared after tooth movement for 1, 2, 4, 8, and 12 weeks. The pulp tissue was characterized for the different groups, with special emphasis on cell density, inflammatory cells, vascularity, and odontoblasts. Dimensions of dentin and the pulpal horns was determined and related with the duration of orthodontic force application and age ware evaluated. We found that neither in young nor in adult rats, force application led to long-lasting or irreversible changes in pulpal tissues. Dimensional variables showed significant age-related changes. In conclusion, orthodontic tooth movement per se has no long-lasting or irreversible effect on pulpal tissues, neither in the young nor in the adult animals. PMID- 26855868 TI - A new Lower Triassic ichthyopterygian assemblage from Fossil Hill, Nevada. AB - We report a new ichthyopterygian assemblage from Lower Triassic horizons of the Prida Formation at Fossil Hill in central Nevada. Although fragmentary, the specimens collected so far document a diverse fauna. One partial jaw exhibits isodont dentition with blunt tipped, mesiodistally compressed crowns and striated enamel. These features are shared with the Early Triassic genus Utatsusaurus known from coeval deposits in Japan and British Columbia. An additional specimen exhibits a different dentition characterized by relatively small, rounded posterior teeth resembling other Early Triassic ichthyopterygians, particularly Grippia. This Nevada assemblage marks a southward latitudinal extension for Early Triassic ichthyopterygians along the eastern margin of Panthalassa and indicates repeated trans-hemispheric dispersal events in Early Triassic ichthyopterygians. PMID- 26855869 TI - First insights into the diversity of gill monogeneans of 'Gnathochromis' and Limnochromis (Teleostei, Cichlidae) in Burundi: do the parasites mirror host ecology and phylogenetic history? AB - Monogenea is one of the most species-rich groups of parasitic flatworms worldwide, with many species described only recently, which is particularly true for African monogeneans. For example, Cichlidogyrus, a genus mostly occurring on African cichlids, comprises more than 100 nominal species. Twenty-two of these have been described from Lake Tanganyika, a famous biodiversity hotspot in which many vertebrate and invertebrate taxa, including monogeneans, underwent unique and spectacular radiations. Given their often high degrees of host specificity, parasitic monogeneans were also used as a potential tool to uncover host species relationships. This study presents the first investigation of the monogenean fauna occurring on the gills of endemic 'Gnathochromis' species along the Burundese coastline of Lake Tanganyika. We test whether their monogenean fauna reflects the different phylogenetic position and ecological niche of 'Gnathochromis' pfefferi and Gnathochromis permaxillaris. Worms collected from specimens of Limnochromis auritus, a cichlid belonging to the same cichlid tribe as G. permaxillaris, were used for comparison. Morphological as well as genetic characterisation was used for parasite identification. In total, all 73 Cichlidogyrus individuals collected from 'G.' pfefferi were identified as C. irenae. This is the only representative of Cichlidogyrus previously described from 'G.' pfefferi, its type host. Gnathochromis permaxillaris is infected by a species of Cichlidogyrus morphologically very similar to C. gillardinae. The monogenean species collected from L. auritus is considered as new for science, but sample size was insufficient for a formal description. Our results confirm previous suggestions that 'G.' pfefferi as a good disperser is infected by a single monogenean species across the entire Lake Tanganyika. Although G. permaxillaris and L. auritus are placed in the same tribe, Cichlidogyrus sp. occurring on G. permaxillaris is morphologically more similar to C. irenae from 'G.' pfefferi, than to the Cichlidogyrus species found on L. auritus. Various evolutionary processes, such as host-switching or duplication events, might underlie the pattern observed in this particular parasite-host system. Additional samples for the Cichlidogyrus species occuring on G. permaxillaris and L. auritus are needed to unravel their evolutionary history by means of (co-)phylogenetic analyses. PMID- 26855870 TI - Climate envelope predictions indicate an enlarged suitable wintering distribution for Great Bustards (Otis tarda dybowskii) in China for the 21st century. AB - The rapidly changing climate makes humans realize that there is a critical need to incorporate climate change adaptation into conservation planning. Whether the wintering habitats of Great Bustards (Otis tarda dybowskii), a globally endangered migratory subspecies whose population is approximately 1,500-2,200 individuals in China, would be still suitable in a changing climate environment, and where this could be found, is an important protection issue. In this study, we selected the most suitable species distribution model for bustards using climate envelopes from four machine learning models, combining two modelling approaches (TreeNet and Random Forest) with two sets of variables (correlated variables removed or not). We used common evaluation methods area under the receiver operating characteristic curves (AUC) and the True Skill Statistic (TSS) as well as independent test data to identify the most suitable model. As often found elsewhere, we found Random Forest with all environmental variables outperformed in all assessment methods. When we projected the best model to the latest IPCC-CMIP5 climate scenarios (Representative Concentration Pathways (RCPs) 2.6, 4.5 and 8.5 in three Global Circulation Models (GCMs)), and averaged the project results of the three models, we found that suitable wintering habitats in the current bustard distribution would increase during the 21st century. The Northeast Plain and the south of North China were projected to become two major wintering areas for bustards. However, the models suggest that some currently suitable habitats will experience a reduction, such as Dongting Lake and Poyang Lake in the Middle and Lower Yangtze River Basin. Although our results suggested that suitable habitats in China would widen with climate change, greater efforts should be undertaken to assess and mitigate unstudied human disturbance, such as pollution, hunting, agricultural development, infrastructure construction, habitat fragmentation, and oil and mine exploitation. All of these are negatively and intensely linked with global change. PMID- 26855871 TI - The Tibetan medicine Zuotai influences clock gene expression in the liver of mice. AB - Background. The circadian clock is involved in drug metabolism, efficacy and toxicity. Drugs could in turn affect the biological clock as a mechanism of their actions. Zuotai is an essential component of many popular Tibetan medicines for sedation, tranquil and "detoxification," and is mainly composed of metacinnabar (beta-HgS). The pharmacological and/or toxicological basis of its action is unknown. This study aimed to examine the effect of Zuotai on biological clock gene expression in the liver of mice. Materials and methods. Mice were orally given Zuotai (10 mg/kg, 1.5-fold of clinical dose) daily for 7 days, and livers were collected every 4 h during the 24 h period. Total RNA was extracted and subjected to real-time RT-PCR analysis of circadian clock gene expression. Results. Zuotai decreased the oscillation amplitude of the clock core gene Clock, neuronal PAS domain protein 2 (Npas2), Brain and muscle Arnt-like protein-1 (Bmal1) at 10:00. For the clock feedback negative control genes, Zuotai had no effect on the oscillation of the clock gene Cryptochrome (Cry1) and Period genes (Per1-3). For the clock-driven target genes, Zuotai increased the oscillation amplitude of the PAR-bZip family member D-box-binding protein (Dbp), decreased nuclear factor interleukin 3 (Nfil3) at 10:00, but had no effect on thyrotroph embryonic factor (Tef); Zuotai increased the expression of nuclear receptor Rev Erbalpha (Nr1d1) at 18:00, but had little influence on the nuclear receptor Rev Erbbeta (Nr1d2) and RORalpha. Conclusion. The Tibetan medicine Zuotai could influence the expression of clock genes, which could contribute to pharmacological and/or toxicological effects of Zuotai. PMID- 26855873 TI - Exploration of the "larval pool": development and ground-truthing of a larval transport model off leeward Hawai'i. AB - Most adult reef fish show site fidelity thus dispersal is limited to the mobile larval stage of the fish, and effective management of such species requires an understanding of the patterns of larval dispersal. In this study, we assess larval reef fish distributions in the waters west of the Big Island of Hawai'i using both in situ and model data. Catches from Cobb midwater trawls off west Hawai'i show that reef fish larvae are most numerous in offshore waters deeper than 3,000 m and consist largely of pre-settlement Pomacanthids, Acanthurids and Chaetodontids. Utilizing a Lagrangian larval dispersal model, we were able to replicate the observed shore fish distributions from the trawl data and we identified the 100 m depth strata as the most likely depth of occupancy. Additionally, our model showed that for larval shore fish with a pelagic larval duration longer than 40 days there was no significant change in settlement success in our model. By creating a general additive model (GAM) incorporating lunar phase and angle we were able to explain 67.5% of the variance between modeled and in situ Acanthurid abundances. We took steps towards creating a predictive larval distribution model that will greatly aid in understanding the spatiotemporal nature of the larval pool in west Hawai'i, and the dispersal of larvae throughout the Hawaiian archipelago. PMID- 26855872 TI - Estimating and comparing microbial diversity in the presence of sequencing errors. AB - Estimating and comparing microbial diversity are statistically challenging due to limited sampling and possible sequencing errors for low-frequency counts, producing spurious singletons. The inflated singleton count seriously affects statistical analysis and inferences about microbial diversity. Previous statistical approaches to tackle the sequencing errors generally require different parametric assumptions about the sampling model or about the functional form of frequency counts. Different parametric assumptions may lead to drastically different diversity estimates. We focus on nonparametric methods which are universally valid for all parametric assumptions and can be used to compare diversity across communities. We develop here a nonparametric estimator of the true singleton count to replace the spurious singleton count in all methods/approaches. Our estimator of the true singleton count is in terms of the frequency counts of doubletons, tripletons and quadrupletons, provided these three frequency counts are reliable. To quantify microbial alpha diversity for an individual community, we adopt the measure of Hill numbers (effective number of taxa) under a nonparametric framework. Hill numbers, parameterized by an order q that determines the measures' emphasis on rare or common species, include taxa richness (q = 0), Shannon diversity (q = 1, the exponential of Shannon entropy), and Simpson diversity (q = 2, the inverse of Simpson index). A diversity profile which depicts the Hill number as a function of order q conveys all information contained in a taxa abundance distribution. Based on the estimated singleton count and the original non-singleton frequency counts, two statistical approaches (non-asymptotic and asymptotic) are developed to compare microbial diversity for multiple communities. (1) A non-asymptotic approach refers to the comparison of estimated diversities of standardized samples with a common finite sample size or sample completeness. This approach aims to compare diversity estimates for equally-large or equally-complete samples; it is based on the seamless rarefaction and extrapolation sampling curves of Hill numbers, specifically for q = 0, 1 and 2. (2) An asymptotic approach refers to the comparison of the estimated asymptotic diversity profiles. That is, this approach compares the estimated profiles for complete samples or samples whose size tends to be sufficiently large. It is based on statistical estimation of the true Hill number of any order q >= 0. In the two approaches, replacing the spurious singleton count by our estimated count, we can greatly remove the positive biases associated with diversity estimates due to spurious singletons and also make fair comparisons across microbial communities, as illustrated in our simulation results and in applying our method to analyze sequencing data from viral metagenomes. PMID- 26855874 TI - New material and revision of Melanorosaurus thabanensis, a basal sauropodomorph from the Upper Triassic of Lesotho. AB - Melanorosaurus is a genus of basal sauropodomorph that currently includes two species from Southern Africa. In this paper, we redescribe the holotype femur of Melanorosaurus thabanensis from the Elliot Formation of Lesotho, as well as associated remains. The stratigraphic position of this taxon is reviewed, and it is clear that it comes from the Lower Elliot Formation being, therefore, Late Triassic in age, and not Early Jurassic as originally described. The knowledge of the anatomy of the basal sauropodomorph of Thabana Morena is enhanced by the description of six new skeletal elements from the type locality. The femur and the ilium from Thabana Morena are diagnostic and characterized by unusual proportions. The first phylogenetic analysis including both this specimen and Melanorosaurus is conducted. This analysis leads to the conclusion that the femur described in the original publication of Melanorosaurus thabanensis can no longer be referred to Melanorosaurus. For these reasons, we hereby create Meroktenos gen. nov. to encompass Meroktenos thabanensis comb. nov. PMID- 26855876 TI - Late Pleistocene fishes of the Tennessee River Basin: an analysis of a late Pleistocene freshwater fish fauna from Bell Cave (site ACb-2) in Colbert County, Alabama, USA. AB - The Tennessee River Basin is considered one of the most important regions for freshwater biodiversity anywhere on the globe. The Tennessee River Basin currently includes populations of at least half of the described contemporary diversity of extant North American freshwater fishes, crayfish, mussel, and gastropod species. However, comparatively little is known about the biodiversity of this basin from the Pleistocene Epoch, particularly the late Pleistocene (~10,000 to 30,000 years B.P.) leading to modern Holocene fish diversity patterns. The objective of this study was to describe the fish assemblages of the Tennessee River Basin from the late Pleistocene using a series of faunas from locales throughout the basin documented from published literature, unpublished reports, and an undocumented fauna from Bell Cave (site ACb-2, Colbert County, AL). Herein we discuss 41 unequivocal taxa from 10 late Pleistocene localities within the basin and include a systematic discussion of 11 families, 19 genera, and 24 identifiable species (28 unequivocal taxa) specific to the Bell Cave locality. Among the described fauna are several extirpated (e.g., Northern Pike Esox lucius, Northern Madtom Noturus stigmosus) and a single extinct (Harelip Sucker Moxostoma lacerum) taxa that suggest a combination of late Pleistocene displacement events coupled with more recent changes in habitat that have resulted in modern basin diversity patterns. The Bell Cave locality represents one of the most intact Pleistocene freshwater fish deposits anywhere in North America. Significant preservational, taphonomic, sampling, and identification biases preclude the identification of additional taxa. Overall, this study provides a detailed look into paleo-river ecology, as well as freshwater fish diversity and distribution leading up to the contemporary biodiversity patterns of the Tennessee River Basin and Mississippi River Basin as a whole. PMID- 26855875 TI - Poultry consumption and prostate cancer risk: a meta-analysis. AB - Background. Several kinds of foods are hypothesized to be potential factors contributing to the variation of prostate cancer (PCa) incidence. But the effect of poultry on PCa is still inconsistent and no quantitative assessment has been published up to date. So we conducted this meta-analysis to clarify the association between them. Materials and Methods. We conducted a literature search of PubMed and Embase for studies examining the association between poultry consumption and PCa up to June, 2015. Pooled risk ratio (RR) and corresponding 95% confidence interval (CI) of the highest versus lowest poultry consumption categories were calculated by fixed-effect model or random-effect model. Results. A total of 27 (12 cohort and 15 case-control) studies comprising 23,703 cases and 469,986 noncases were eligible for inclusion. The summary RR of total PCa incidence was 1.03 (95% CI [0.95-1.11]) for the highest versus lowest categories of poultry intake. The heterogeneity between studies was not statistically significant (P = 0.768, I (2) = 28.5%). Synthesized analysis of 11 studies on high stage PCa and 8 studies on chicken exposure also demonstrated null association. We also did not obtain significant association in the subgroup of cohort study (RR = 1.04, 95% CI [0.98-1.10]), as well as in the subgroups of population-based case-control study and hospital-based case-control study. Then the studies were divided into three geographic groups: Western countries, Asia and South America. The pooled RRs in these areas did not reveal statistically significant association between poultry and PCa. Conclusions. This meta-analysis suggests no association between poultry consumption and PCa risk. Further well designed studies are warranted to confirm the result. PMID- 26855877 TI - Patterns of bird-window collisions inform mitigation on a university campus. AB - Bird-window collisions cause an estimated one billion bird deaths annually in the United States. Building characteristics and surrounding habitat affect collision frequency. Given the importance of collisions as an anthropogenic threat to birds, mitigation is essential. Patterned glass and UV-reflective films have been proven to prevent collisions. At Duke University's West campus in Durham, North Carolina, we set out to identify the buildings and building characteristics associated with the highest frequencies of collisions in order to propose a mitigation strategy. We surveyed six buildings, stratified by size, and measured architectural characteristics and surrounding area variables. During 21 consecutive days in spring and fall 2014, and spring 2015, we conducted carcass surveys to document collisions. In addition, we also collected ad hoc collision data year-round and recorded the data using the app iNaturalist. Consistent with previous studies, we found a positive relationship between glass area and collisions. Fitzpatrick, the building with the most window area, caused the most collisions. Schwartz and the Perk, the two small buildings with small window areas, had the lowest collision frequencies. Penn, the only building with bird deterrent pattern, caused just two collisions, despite being almost completely made out of glass. Unlike many research projects, our data collection led to mitigation action. A resolution supported by the student government, including news stories in the local media, resulted in the application of a bird deterrent film to the building with the most collisions: Fitzpatrick. We present our collision data and mitigation result to inspire other researchers and organizations to prevent bird-window collisions. PMID- 26855878 TI - Performance of women with fibromyalgia in walking up stairs while carrying a load. AB - Background. Fibromyalgia is a chronic disease characterized by widespread pain and other associated symptoms. It has a relevant impact on physical fitness and the ability to perform daily living tasks. The objective of the study was to analyze the step-by-step-performance and the trunk tilt of women with fibromyalgia in the 10-step stair climbing test compared with healthy controls. Methods. A cross-sectional study was carried out. Twelve women suffering from fibromyalgia and eight healthy controls were recruited from a local association. Participants were asked to climb 10 stairs without carrying a load and 10 stairs carrying a load of 5 kg in each hand. Mediolateral trunk tilt was assessed using the "Functional Assessment of Biomechanics (FAB)" wireless motion capture device, and the time between steps was assessed via weight-bearing insoles. Results. Trunk tilt in the stair-climbing task carrying a load was significantly higher in women with fibromyalgia when compared to the healthy controls (2.31 (0.63) vs. 1.69 (0.51) respectively). The effect of carrying a load was significantly higher for women with fibromyalgia compared with healthy controls at the intermediate and final part of the task. Discussion. Trunk tilt during stair climbing while carrying a load was higher in women with FM, which could increase the risk of falling. Additionally, women with FM experienced a higher pace slowdown as a consequence of the load, which supports the need of including specific strength and resistance training to physical therapies for this population. PMID- 26855879 TI - Unequal contribution of native South African phylogeographic lineages to the invasion of the African clawed frog, Xenopus laevis, in Europe. AB - Due to both deliberate and accidental introductions, invasive African Clawed Frog (Xenopus laevis) populations have become established worldwide. In this study, we investigate the geographic origins of invasive X. laevis populations in France and Portugal using the phylogeographic structure of X. laevis in its native South African range. In total, 80 individuals from the whole area known to be invaded in France and Portugal were analysed for two mitochondrial and three nuclear genes, allowing a comparison with 185 specimens from the native range. Our results show that native phylogeographic lineages have contributed differently to invasive European X. laevis populations. In Portugal, genetic and historical data suggest a single colonization event involving a small number of individuals from the south-western Cape region in South Africa. In contrast, French invasive X. laevis encompass two distinct native phylogeographic lineages, i.e., one from the south-western Cape region and one from the northern regions of South Africa. The French X. laevis population is the first example of a X. laevis invasion involving multiple lineages. Moreover, the lack of population structure based on nuclear DNA suggests a potential role for admixture within the invasive French population. PMID- 26855881 TI - Structural Properties of High-Energy N12C6 Molecules: Cyclic Hexamers of NCN. AB - Molecules with high nitrogen content are of interest for their potential as high energy materials. However, many molecules with 100% nitrogen content are unstable and dissociate with low barriers, which limits practical applications. In the present study, cyclic hexamers of the basic unit NCN (70% nitrogen by mass) are studied to determine the structural features and bonding characteristics that lead to more stable molecules. Double- and triple-bonded NCN units are compared to determine which form of NCN contributes the greater stability. Theoretical calculations using density functional theory and couple-cluster theory are carried out on a series of N12C6 molecules to determine trends in stability. Energetic and structural trends, as well as differences between DFT and coupled cluster theory, are calculated and discussed. PMID- 26855882 TI - Medication-related cognitive artifacts used by older adults with heart failure. AB - OBJECTIVE: To use a human factors perspective to examine how older adult patients with heart failure use cognitive artifacts for medication management. METHODS: We performed a secondary analysis of data collected from 30 patients and 14 informal caregivers enrolled in a larger study of heart failure self-care. Data included photographs, observation notes, interviews, video recordings, medical record data, and surveys. These data were analyzed using an iterative content analysis. RESULTS: Findings revealed that medication management was complex, inseparable from other patient activities, distributed across people, time, and place, and complicated by knowledge gaps. We identified fifteen types of cognitive artifacts including medical devices, pillboxes, medication lists, and electronic personal health records used for: 1) measurement/evaluation; 2) tracking/communication; 3) organization/administration; and 4) information/sensemaking. These artifacts were characterized by fit and misfit with the patient's sociotechnical system and demonstrated both advantages and disadvantages. We found that patients often modified or "finished the design" of existing artifacts and relied on "assemblages" of artifacts, routines, and actors to accomplish their self-care goals. CONCLUSIONS: Cognitive artifacts are useful but sometimes are poorly designed or are not used optimally. If appropriately designed for usability and acceptance, paper-based and computer-based information technologies can improve medication management for individuals living with chronic illness. These technologies can be designed for use by patients, caregivers, and clinicians; should support collaboration and communication between these individuals; can be coupled with home-based and wearable sensor technology; and must fit their users' needs, limitations, abilities, tasks, routines, and contexts of use. PMID- 26855883 TI - CressInt: a user-friendly web resource for genome-scale exploration of gene regulation in Arabidopsis thaliana. AB - The thale cress Arabidopsis thaliana is a powerful model organism for studying a wide variety of biological processes. Recent advances in sequencing technology have resulted in a wealth of information describing numerous aspects of A. thaliana genome function. However, there is a relative paucity of computational systems for efficiently and effectively using these data to create testable hypotheses. We present CressInt, a user-friendly web resource for exploring gene regulatory mechanisms in A. thaliana on a genomic scale. The CressInt system incorporates a variety of genome-wide data types relevant to gene regulation, including transcription factor (TF) binding site models, ChIP-seq, DNase-seq, eQTLs, and GWAS. We demonstrate the utility of CressInt by showing how the system can be used to (1) Identify TFs binding to the promoter of a gene of interest; (2) identify genetic variants that are likely to impact TF binding based on a ChIP-seq dataset; and (3) identify specific TFs whose binding might be impacted by phenotype-associated variants. CressInt is freely available at http://cressint.cchmc.org. PMID- 26855884 TI - Sex-Dependent effects of developmental arsenic exposure on methylation capacity and methylation regulation of the glucocorticoid receptor system in the embryonic mouse brain. AB - Previously we have shown that prenatal moderate arsenic exposure (50 ppb) disrupts glucocorticoid receptor (GR) programming and that these changes continue into adolescence in males. However, it was not clear what the molecular mechanisms were promoting these GR programming changes or if these changes occurred in arsenic-exposed females. In the present studies, we assessed the effects of arsenic on protein and mRNA of the glucocorticoid receptor (GR) and 11beta-hydroxysteroid dehydrogenase (Hsd) isozymes and compared the levels of methylation within the promoters of the Nr3c1 and Hsd11b1 genes in female fetal brain at embryonic days (E) 14 and 18. Prenatal arsenate exposure produced sex specific effects on the glucocorticoid system. Compared to males, females were resistant to arsenic induced changes in GR, 11beta-Hsd-1 and 11beta-Hsd-2 protein levels despite observed elevations in Nr3c1 and Hsd11b2 mRNA. This sex-specific effect was not due to differences in the methylation of the GR promoter as methylation of the Nr3c1 gene was either unchanged (region containing the egr-1 binding site) or similarly reduced (region containing the SP-1 transcription factor binding site) in both males and females exposed to arsenic. Arsenic did produce sex and age-specific changes in the methylation of Hsd11b1 gene, producing increased methylation in females at E14 and decreased methylation at E18. These changes were not attributed to changes in DNMT levels. Since arsenate metabolism could interfere with the generation of methyl donor groups, we assessed glutathione (GSH), s-adenosylmethionine (SAM) and As 3 methyltransferase (As3MT). Exposed males and females had similar levels of As3MT and SAM; however, females had higher levels of GSH/GSSH. It is possible that this greater anti oxidative capacity within the females provides protection against low to moderate arsenate. Our data suggest that the GR signaling system in female offspring was not as affected by prenatal arsenic and predicts that female arsenic-exposed mice should have normal GR feedback regulation. PMID- 26855885 TI - Development and utilization of complementary communication channels for treatment decision making and survivorship issues among cancer patients: The CIS Research Consortium Experience. AB - OBJECTIVE: Cancer patients and survivors are assuming active roles in decision making and digital patient support tools are widely used to facilitate patient engagement. As part of Cancer Information Service Research Consortium's randomized controlled trials focused on the efficacy of eHealth interventions to promote informed treatment decision-making for newly diagnosed prostate and breast cancer patients, and post-treatment breast cancer, we conducted a rigorous process evaluation to examine the actual use of and perceived benefits of two complementary communication channels -- print and eHealth interventions. METHODS: The three Virtual Cancer Information Service (V-CIS) interventions were developed through a rigorous developmental process, guided by self-regulatory theory, informed decision-making frameworks, and health communications best practices. Control arm participants received NCI print materials; experimental arm participants received the additional V-CIS patient support tool. Actual usage data from the web-based V-CIS was also obtained and reported. RESULTS: Print materials were highly used by all groups. About 60% of the experimental group reported using the V-CIS. Those who did use the V-CIS rated it highly on improvements in knowledge, patient-provider communication and decision-making. CONCLUSION: The findings show that how patients actually use eHealth interventions either singularly or within the context of other communication channels is complex. PRACTICE IMPLICATIONS: Integrating rigorous best practices and theoretical foundations is essential and multiple communication approaches should be considered to support patient preferences. PMID- 26855886 TI - INCREASED INTERNET USE AND POORER ABILITY TO MANAGE EMOTIONS IN YOUTH AT HIGH RISK FOR PSYCHOSIS. AB - The relationship between Internet use and social behavior remains unknown. However, research indicates that Internet use (IU) may have some causal role in certain types of psychopathology and overall functioning. In contrast, other work suggests that IU may be protective and buffer against social isolation. Poorer emotional processing (EP) is characteristic of schizophrenia, and these deficits are present prior to illness onset (the ultra high-risk period (UHR)). UHR adolescents/young adults also fall within an age demographic characterized by extensive IU, which suggests that evaluating a link between IU and social behavior in this population may be especially informative. The present study examined the relationship between IU and emotional processing in 98 adolescents/young adults (52 UHR youth and 46 controls). UHR youth exhibited greater problematic IU (beta = -6.49, F(1,95) = 8.79, p = 0.002) and social withdrawal/problems resulting from this use (beta = -3.23, F(1,95) = 11.43, p < 0.001), as well deficits in emotional processing in comparison to healthy peers (beta = 4.59, F(1,94) = 5.52, p = 0.011). Furthermore, the social problems resulting from IU was significantly related to the ability to process emotional information in the UHR group (beta = -0.51, t(1,48) = -2.10, p = 0.021). UHR youth showed evidence of problematic IU relative to controls, and the social problems resulting from IU related to poorer EP. Findings replicate extant research involving other psychosis risk populations, while adding information regarding how social processes may relate to IU. PMID- 26855887 TI - New pharmacological approaches against chronic bowel and bladder problems in paralytics. AB - Spinal cord injury (SCI) leads generally to an irreversible loss of sensory functions and voluntary motor control below injury level. Cures that could repair SCI and/or restore voluntary walking have not been yet developed nor commercialized. Beyond the well-known loss of walking capabilities, most SCI patients experience also a plethora of motor problems and health concerns including specific bladder and bowel dysfunctions. Indeed, chronic constipation and urinary retention, two significant life-threatening complications, are typically found in patients suffering of traumatic (e.g., falls or car accidents) or non-traumatic SCI (e.g., multiple sclerosis, spinal tumors). Secondary health concerns associated with these dysfunctions include hemorrhoids, abdominal distention, altered visceral sensitivity, hydronephrosis, kidney failure, urinary tract infections, sepsis and, in some cases, cardiac arrest. Consequently, individuals with chronic SCI are forced to regularly seek emergency and critical care treatments when some of these conditions occur or become intolerable. Increasing evidence supports the existence of a novel experimental approach that may be capable of preventing the occurrence or severity of bladder and bowel problems. Indeed, recent findings in animal models of SCI have revealed that, despite paraplegia or tetraplegia, it remains possible to elicit episodes of micturition and defecation by acting pharmacologically or electrically upon specialized lumbosacral neuronal networks, namely the spinal or sacral micturition center (SMC) and lumbosacral defecation center (LDC). Daily activation of SMC and LDC neurons could potentially become, new classes of minimally invasive treatments (i.e., if orally active) against these dysfunctions and their many life-threatening complications. PMID- 26855888 TI - Optimizing the value of measuring inferior vena cava diameter in shocked patients. AB - Point-of-care ultrasound has been increasingly used in evaluating shocked patients including the measurement of inferior vena cava (IVC) diameter. Operators should standardize their technique in scanning IVC. Relative changes are more important than absolute numbers. We advise using the longitudinal view (B mode) to evaluate the gross collapsibility, and the M mode to measure the IVC diameter. Combining the collapsibility and diameter size will increase the value of IVC measurement. This approach has been very useful in the resuscitation of shocked patients, monitoring their fluid demands, and predicting recurrence of shock. Pitfalls in measuring IVC diameter include increased intra-thoracic pressure by mechanical ventilation or increased right atrial pressure by pulmonary embolism or heart failure. The IVC diameter is not useful in cases of increased intra-abdominal pressure (abdominal compartment syndrome) or direct pressure on the IVC. The IVC diameter should be combined with focused echocardiography and correlated with the clinical picture as a whole to be useful. PMID- 26855889 TI - Advanced trauma life support training: How useful it is? AB - We have tried in a recently published systematic review (World J of Surg 2014; 38: 322-329) to study the educational value of advanced trauma life support (ATLS) courses and whether they improve survival of multiple trauma patients. This Frontier article summarizes what we have learned and reflects on future perspectives in this important area. Our recently published systematic review has shown that ATLS training is very useful from an educational point view. It significantly increased knowledge, and improved practical skills and the critical decision making process in managing multiple trauma patients. These positive changes were evident in a wide range of learners including undergraduate medical students and postgraduate residents from different subspecialties. In contrast, clear evidence that ATLS training reduces trauma death is lacking. It is obvious that it is almost impossible to perform randomized controlled trials to study the effect of ATLS courses on trauma mortality. Studying factors predicting trauma mortality is a very complex issue. Accordingly, trauma mortality does not depend solely on ATLS training but on other important factors, like presence of well developed trauma systems including advanced pre-hospital care. We think that the way to answer whether ATLS training improves survival is to perform large prospective cohort studies of high quality data and use advanced statistical modelling. PMID- 26855890 TI - Antithrombin in the treatment of burn trauma. AB - Antithrombin (AT) is a natural anticoagulant with anti-inflammatory properties that has demonstrated value in sepsis, disseminated intravascular coagulation and in burn and inhalation injury. With high doses, AT may decrease blood loss during eschar excision, reducing blood transfusion requirements. There are no human randomized, placebo-controlled studies, which have tested the true benefit of this agent in these conditions. Two main forms of AT are either plasma-derived AT (phAT) and recombinant AT (rhAT). Major ovine studies in burn and smoke inhalation injury have utilized rhAT. There have been no studies which have either translated the basic rhAT research in burn trauma, or determined the tolerance and pharmacokinetics of rhAT concentrate infusions in burn patients. Advantages of rhAT infusions are no risk of blood borne diseases and lower cost. However, the majority of human burn patient studies have been conducted utilizing phAT. Recent Japanese clinical trials have started using phAT in abdominal sepsis successfully. This review examines the properties of both phAT and rhAT, and analyzes studies in which they have been utilized. We believe that it is time to embark on a randomized placebo-controlled multi-center trial to establish the role of AT in both civilian and military patients with burn trauma. PMID- 26855891 TI - Alcoholism and critical illness: A review. AB - Alcohol is the most commonly used and abused drug in the world, and alcohol use disorders pose a tremendous burden to healthcare systems around the world. The lifetime prevalence of alcohol abuse in the United States is estimated to be around 18%, and the economic consequences of these disorders are staggering. Studies on hospitalized patients demonstrate that about one in four patients admitted to critical care units will have alcohol-related issues, and unhealthy alcohol consumption is responsible for numerous clinical problems encountered in intensive care unit (ICU) settings. Patients with alcohol use disorders are not only predisposed to developing withdrawal syndromes and other conditions that often require intensive care, they also experience a considerably higher rate of complications, longer ICU and hospital length of stay, greater resource utilization, and significantly increased mortality compared to similar critically ill patients who do not abuse alcohol. Specific disorders seen in the critical care setting that are impacted by alcohol abuse include delirium, pneumonia, acute respiratory distress syndrome, sepsis, gastrointestinal hemorrhage, trauma, and burn injuries. Despite the substantial burden of alcohol-induced disease in these settings, critical care providers often fail to identify individuals with alcohol use disorders, which can have significant implications for this vulnerable population and delay important clinical interventions. PMID- 26855892 TI - Neuroprotective measures in children with traumatic brain injury. AB - Traumatic brain injury (TBI) is a major cause of death and disability in children. Severe TBI is a leading cause of death and often leads to life changing disabilities in survivors. The modern management of severe TBI in children on intensive care unit focuses on preventing secondary brain injury to improve outcome. Standard neuroprotective measures are based on management of intracranial pressure (ICP) and cerebral perfusion pressure (CPP) to optimize the cerebral blood flow and oxygenation, with the intention to avoid and minimise secondary brain injury. In this article, we review the current trends in management of severe TBI in children, detailing the general and specific measures followed to achieve the desired ICP and CPP goals. We discuss the often limited evidence for these therapeutic interventions in children, extrapolation of data from adults, and current recommendation from paediatric guidelines. We also review the recent advances in understanding the intracranial physiology and neuroprotective therapies, the current research focus on advanced and multi-modal neuromonitoring, and potential new therapeutic and prognostic targets. PMID- 26855894 TI - Prevention of stress-related ulcer bleeding at the intensive care unit: Risks and benefits of stress ulcer prophylaxis. AB - Stress-related mucosal disease is a typical complication of critically ill patients in the intensive care unit (ICU). It poses a risk of clinically relevant upper gastrointestinal (GI) bleeding. Therefore, stress ulcer prophylaxis (SUP) is recommended in high-risk patients, especially those mechanically ventilated > 48 h and those with a manifest coagulopathy. Proton pump inhibitors (PPI) and, less effectively, histamine 2 receptor antagonists (H2RA) prevent GI bleeding in critically ill patients in the ICU. However, the routine use of pharmacological SUP does not reduce overall mortality in ICU patients. Moreover, recent studies revealed that SUP in the ICU might be associated with potential harm such as an increased risk of infectious complications, especially nosocomial pneumonia and Clostridium difficile-associated diarrhea. Additionally, special populations such as patients with liver cirrhosis may even have an increased mortality rate if treated with PPI. Likewise, PPI can be toxic for both the liver and the bone marrow, and some PPI show clinically relevant interactions with important other drugs like clopidogrel. Therefore, the agent of choice, the specific balance of risks and benefits for individual patients as well as the possible dose of PPI has to be chosen carefully. Alternatives to PPI prophylaxis include H2RA and/or sucralfate. Instead of routine SUP, further trials should investigate risk adjusted algorithms, balancing benefits and threats of SUP medication in the ICU. PMID- 26855893 TI - Use of venous-to-arterial carbon dioxide tension difference to guide resuscitation therapy in septic shock. AB - The mixed venous-to-arterial carbon dioxide (CO2) tension difference [P (v-a) CO2] is the difference between carbon dioxide tension (PCO2) in mixed venous blood (sampled from a pulmonary artery catheter) and the PCO2 in arterial blood. P (v-a) CO2 depends on the cardiac output and the global CO2 production, and on the complex relationship between PCO2 and CO2 content. Experimental and clinical studies support the evidence that P (v-a) CO2 cannot serve as an indicator of tissue hypoxia, and should be regarded as an indicator of the adequacy of venous blood to wash out the total CO2 generated by the peripheral tissues. P (v-a) CO2 can be replaced by the central venous-to-arterial CO2 difference (DeltaPCO2), which is calculated from simultaneous sampling of central venous blood from a central vein catheter and arterial blood and, therefore, more easy to obtain at the bedside. Determining the DeltaPCO2 during the resuscitation of septic shock patients might be useful when deciding when to continue resuscitation despite a central venous oxygen saturation (ScvO2) > 70% associated with elevated blood lactate levels. Because high blood lactate levels is not a discriminatory factor in determining the source of that stress, an increased DeltaPCO2 (> 6 mmHg) could be used to identify patients who still remain inadequately resuscitated. Monitoring the DeltaPCO2 from the beginning of the reanimation of septic shock patients might be a valuable means to evaluate the adequacy of cardiac output in tissue perfusion and, thus, guiding the therapy. In this respect, it can aid to titrate inotropes to adjust oxygen delivery to CO2 production, or to choose between hemoglobin correction or fluid/inotrope infusion in patients with a too low ScvO2 related to metabolic demand. The combination of P (v-a) CO2 or DeltaPCO2 with oxygen-derived parameters through the calculation of the P (v-a) CO2 or DeltaPCO2/arteriovenous oxygen content difference ratio can detect the presence of global anaerobic metabolism. PMID- 26855896 TI - Preemptive mechanical ventilation can block progressive acute lung injury. AB - Mortality from acute respiratory distress syndrome (ARDS) remains unacceptable, approaching 45% in certain high-risk patient populations. Treating fulminant ARDS is currently relegated to supportive care measures only. Thus, the best treatment for ARDS may lie with preventing this syndrome from ever occurring. Clinical studies were examined to determine why ARDS has remained resistant to treatment over the past several decades. In addition, both basic science and clinical studies were examined to determine the impact that early, protective mechanical ventilation may have on preventing the development of ARDS in at-risk patients. Fulminant ARDS is highly resistant to both pharmacologic treatment and methods of mechanical ventilation. However, ARDS is a progressive disease with an early treatment window that can be exploited. In particular, protective mechanical ventilation initiated before the onset of lung injury can prevent the progression to ARDS. Airway pressure release ventilation (APRV) is a novel mechanical ventilation strategy for delivering a protective breath that has been shown to block progressive acute lung injury (ALI) and prevent ALI from progressing to ARDS. ARDS mortality currently remains as high as 45% in some studies. As ARDS is a progressive disease, the key to treatment lies with preventing the disease from ever occurring while it remains subclinical. Early protective mechanical ventilation with APRV appears to offer substantial benefit in this regard and may be the prophylactic treatment of choice for preventing ARDS. PMID- 26855895 TI - Respiratory mechanics in brain injury: A review. AB - Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients. PMID- 26855897 TI - Critical care of obese patients during and after spine surgery. AB - Obesity is one of the most prevalent health problems facing the United States today, with a recent JAMA article published in 2014 estimating the prevalence of one third of all adults in the United States being obese. Also, due to technological advancements, the incidence of spine surgeries is growing. Considering these overall increases in both obesity and the performance of spinal surgeries, it can be inferred that more spinal surgery candidates will be obese. Due to this, certain factors must be taken into consideration when dealing with spine surgeries in the obese. Obesity is closely correlated with additional medical comorbidities, including hypertension, coronary artery disease, congestive heart failure, and diabetes mellitus. The pre-operative evaluation may be more difficult, as a more extensive medical evaluation may be needed. Also, adequate radiographic images can be difficult to obtain due to patient size and equipment limitations. Administering anesthesia becomes more difficult, as does proper patient positioning. Post-operatively, the obese patient is at greater risk for reintubation, difficulty with pain control, wound infection and deep vein thrombosis. However, despite these concerns, appropriate clinical outcomes can still be achieved in the obese spine surgical candidate. Obesity, therefore, is not a contraindication to spine surgery, and appropriate patient selection remains the key to obtaining favorable clinical outcomes. PMID- 26855898 TI - Corticosteroids for severe influenza pneumonia: A critical appraisal. AB - Influenza pneumonia is associated with high number of severe cases requiring hospital and intensive care unit (ICU) admissions with high mortality. Systemic steroids are proposed as a valid therapeutic option even though its effects are still controversial. Heterogeneity of published data regarding study design, population demographics, severity of illness, dosing, type and timing of corticosteroids administered constitute an important limitation for drawing robust conclusions. However, it is reasonable to admit that, as it was not found any advantage of corticosteroid therapy in so diverse conditions, such beneficial effects do not exist at all. Its administration is likely to increase overall mortality and such trend is consistent regardless of the quality as well as the sample size of studies. Moreover it was shown that corticosteroids might be associated with higher incidence of hospital-acquired pneumonia and longer duration of mechanical ventilation and ICU stay. Finally, it is reasonable to conclude that corticosteroids failed to demonstrate any beneficial effects in the treatment of patients with severe influenza infection. Thus its current use in severe influenza pneumonia should be restricted to very selected cases and in the setting of clinical trials. PMID- 26855899 TI - Mild to moderate intra-abdominal hypertension: Does it matter? AB - This review summarizes the epidemiology, pathophysiological consequences and impact on outcome of mild to moderate (Grade I to II) intra-abdominal hypertension (IAH), points out possible pitfalls in available treatment recommendations and focuses on tasks for future research in the field. IAH occurs in about 40% of ICU patients. Whereas the prevalence of abdominal compartment syndrome seems to be decreasing, the prevalence of IAH does not. More than half of IAH patients present with IAH grade I and approximately a quarter with IAH grade II. However, most of the studies have addressed IAH as a yes-or-no variable, with little or no attention to different severity grades. Even mild IAH can have a negative impact on tissue perfusion and microcirculation and be associated with an increased length of stay and duration of mechanical ventilation. However, the impact of IAH and its different grades on mortality is controversial. The influence of intra-abdominal pressure (IAP) on outcome most likely depends on patient and disease characteristics and the concomitant macro- and microcirculation. Therefore, management might differ significantly. Today, clear triggers for interventions in different patient groups with mild to moderate IAH are not defined. Further studies are needed to clarify the clinical importance of mild to moderate IAH identifying clear triggers for interventions to lower the IAP. PMID- 26855900 TI - Prognostic factors associated with hospital survival in comatose survivors of cardiac arrest. AB - AIM: To identify patient, cardiac arrest and management factors associated with hospital survival in comatose survivors of cardiac arrest. METHODS: A retrospective, single centre study of comatose patients admitted to our intensive care unit (ICU) following cardiac arrest during the twenty year period between 1993 and 2012. This study was deemed by the Human Research Ethics Committee (HREC) of Monash Health to be a quality assurance exercise, and thus did not require submission to the Monash Health HREC (Research Project Application, No. 13290Q). The study population included all patients admitted to our ICU between 1993 and 2012, with a discharge diagnosis including "cardiac arrest". Patients were excluded if they did not have a cardiac arrest prior to ICU admission (i.e., if their primary arrest was during their admission to ICU), or were not comatose on arrival to ICU. Our primary outcome measure was survival to hospital discharge. Secondary outcome measures were ICU and hospital length of stay (LOS), and factors associated with survival to hospital discharge. RESULTS: Five hundred and eighty-two comatose patients were admitted to our ICU following cardiac arrest, with 35% surviving to hospital discharge. The median ICU and hospital LOS was 3 and 5 d respectively. There was no survival difference between in-hospital and out-of-hospital cardiac arrests. Males made up 62% of our cardiac arrest population, were more likely to have a shockable rhythm (56% vs 37%, P < 0.001), and were more likely to survive to hospital discharge (40% vs 28%, P = 0.006). On univariate analysis, therapeutic hypothermia, regardless of method used (e.g., rapid infusion of ice cold fluids, topical ice, "Arctic Sun", passive rewarming, "Bair Hugger") and location initiated (e.g., pre-hospital, emergency department, intensive care) was associated with increased survival. There was however no difference in survival associated with target temperature, time at target temperature, location of initial cooling, method of initiating cooling, method of maintaining cooling or method of rewarming. Patients that survived were more likely to have a shockable rhythm (P < 0.001), shorter time to return of spontaneous circulation (P < 0.001), receive therapeutic hypothermia (P = 0.03), be of male gender (P = 0.006) and have a lower APACHE II score (P < 0.001). After multivariate analysis, only a shockable initial rhythm (OR = 6.4, 95%CI: 3.95 10.4; P < 0.01) and a shorter time to return of spontaneous circulation (OR = 0.95, 95%CI: 0.93-0.97; P < 0.01) was found to be independently associated with survival to hospital discharge. CONCLUSION: In comatose survivors of cardiac arrest, shockable rhythm and shorter time to return of spontaneous circulation were independently associated with increased survival to hospital discharge. PMID- 26855902 TI - Risk-reducing, conservative mastectomy-analysis of surgical outcome and quality of life in 272 implant-based reconstructions using TiLoop((r)) Bra versus autologous corial flaps. AB - BACKGROUND: Different approaches have evolved for conservative mastectomies, mostly according to surgeon's preference. Patients' perspective was not always in the primary focus. BRCA status has drawn much attention and therapeutic as well as prophylactic mastectomies are rising. However, knowledge on quality of life (QoL) thereafter is limited. We investigated the surgical and patient reported outcome of conservative mastectomies with implants and TiLoop((r)) Bra vs. corial flaps. METHODS: Conservative mastectomies were analyzed from a prospectively maintained database in a unicentric study of consecutive 272 reconstructions from 2000-2014. We used four validated QoL questionnaires: FACT-G, EORTC C-30, EORTC B 23 and Breast Cancer Treatment Outcome Scale (BCTOS). The use of TiLoop((r)) Bra, a titanized polypropylene mesh, for lower breast pole coverage was compared to autologous corial flaps. RESULTS: A total of 217 patients with 272 conservative mastectomies (55 bilateral) were included. Median follow-up was 3.5 years (range, 0-14 years). Skin-sparing mastectomy (SSM) was performed in 131 patients and subcutaneous mastectomy (SCM) in 86 patients. Invasive breast-cancer was the indication for surgery in 106 patients, non-invasive breast cancer (DCIS) in 80 patients, prophylactic indication (BRCA1/2-mutation) in 30 patients and contralateral alignment in 1 patient. TiLoop((r)) Bra was used in 78 and corial flap in 79 patients. Response to questionnaires was 70%. TiLoop((r)) Bra improved aesthetic results (P=0.049) and prevented implant dislocation (P=0.009). All patients expressed their adherence to the decision for surgery. Patients with SCM expressed their satisfaction even to a higher extent than those with SSM, particulary with regard to symmetry (P=0.018) and scars (P=0.037). CONCLUSIONS: QoL after conservative mastectomies is demonstrated as excellent in several validated QoL-instruments. Double-plane technique for coverage of the implant yields good results with autologous corial flaps and Tiloop((r)) Bra, favouring the latter in terms of aesthetics and prevention of implant dislocation. PMID- 26855901 TI - Field expansion of DNA polymerase chain reaction for early infant diagnosis of HIV-1: The Ethiopian experience. AB - BACKGROUND: Early diagnosis of infants infected with HIV (EID) and early initiation of treatment significantly reduces the rate of disease progression and mortality. One of the challenges to identification of HIV-1-infected infants is availability and/or access to quality molecular laboratory facilities which perform molecular virologic assays suitable for accurate identification of the HIV status of infants. METHOD: We conducted a joint site assessment and designed laboratories for the expansion of DNA polymerase chain reaction (PCR) testing based on dried blood spot (DBS) for EID in six regions of Ethiopia. Training of appropriate laboratory technologists and development of required documentation including standard operating procedures (SOPs) was carried out. The impact of the expansion of EID laboratories was assessed by the number of tests performed as well as the turn-around time. RESULTS: DNA PCR for EID was introduced in 2008 in six regions. From April 2006 to April 2008, a total of 2848 infants had been tested centrally at the Ethiopian Health and Nutrition Research Institute (EHNRI) in Addis Ababa, and which was then the only laboratory with the capability to perform EID; 546 (19.2%) of the samples were positive. By November 2010, EHNRI and the six laboratories had tested an additional 16 985 HIV-exposed infants, of which 1915 (11.3%) were positive. The median turn-around time for test results was 14 days (range 14-21 days). CONCLUSION: Expansion of HIV DNA PCR testing facilities that can provide quality and reliable results is feasible in resource limited settings. Regular supervision and monitoring for quality assurance of these laboratories is essential to maintain accuracy of testing. PMID- 26855903 TI - Preoperative digital mammography imaging in conservative mastectomy and immediate reconstruction. AB - BACKGROUND: Digital mammography clearly distinguishes gland tissue density from the overlying non-glandular breast tissue coverage, which corresponds to the existing tissue between the skin and the Cooper's ligaments surrounding the gland (i.e., dermis and subcutaneous fat). Preoperative digital imaging can determine the thickness of this breast tissue coverage, thus facilitating planning of the most adequate surgical techniques and reconstructive procedures for each case. METHODS: This study aimed to describe the results of a retrospective study of 352 digital mammograms in 176 patients with different breast volumes who underwent preoperative conservative mastectomies. The breast tissue coverage thickness and its relationship with the breast volume were evaluated. RESULTS: The breast tissue coverage thickness ranged from 0.233 to 4.423 cm, with a mean value of 1.952 cm. A comparison of tissue coverage and breast volume revealed a non-direct relationship between these factors. CONCLUSIONS: Preoperative planning should not depend only on breast volume. Flap evaluations based on preoperative imaging measurements might be helpful when planning a conservative mastectomy. Accordingly, we propose a breast tissue coverage classification (BTCC). PMID- 26855904 TI - Effect of young age, positive margins, and triple negative status on disease recurrence after breast conserving therapy. AB - BACKGROUND: To determine the risk factors for disease recurrence after breast conserving therapy (BCT) for breast cancer in a group of South-East Asian women. METHODS: Medical and pathological records of women who underwent BCT during the 10-year period from 2001 to 2010 were reviewed. Data collected included age <=35 years defined as the young, type of operation, pathological data, hormonal receptor (HR) status, human epidermal growth factor receptor-2 (HER-2) expression status, and surgical margin status. Data on adjuvant therapy were also collected. Main outcomes were overall breast cancer recurrence, locoregional, and distant recurrence. Risk factors for each type of recurrence were identified using Cox proportional hazards regression models. RESULTS: There were 294 BCTs in 290 patients during the study period. The overwhelming majority (91%) had early stage (stages I-II) breast cancers. Young age patients constituted 9% of all patients, and triple negative cancers (HR negative and HER-2 negative) were seen in 19%. Involved margins on initial surgery were found in 9% of cases, and after reoperation, only 2% had involved margins. After a median follow-up of 50 months, and a maximum follow-up of 135 months, there were 30 recurrences and 6 deaths. Of the 30 recurrences, 19 included locoregional, 20 included distant, and 13 had in breast recurrences. The disease-free survival at 10 years was 82.5% (95% CI: 74.8% to 88.1%), and the cumulative in-breast recurrence was 9.3% (95% CI: 4.9% to 17.2%) at 10 years. Multivariable Cox regression analysis revealed that young age, larger tumor size, involved margins, and no breast irradiation were associated with higher risk of locoregional recurrence. Triple negative status, larger tumor size, more positive nodes, and involved margins were associated with higher risk of distant recurrence. CONCLUSIONS: We found young age to be a significant prognosticator of locoregional recurrence, and triple negative status of distant recurrence. Involved surgical margin status was associated with both recurrences. Tumor size was associated with both recurrences, and axillary lymph node metastasis was associated with distant recurrence. PMID- 26855905 TI - Conservative mastectomies and Immediate-DElayed AutoLogous (IDEAL) breast reconstruction: the DIEP flap. AB - BACKGROUND: With the development of conservative mastectomies, there are an increasing number of women seeking immediate implant based and autologous breast reconstruction. Despite the oncologic safety of the procedures, the focus will be on the timing of reconstruction. METHODS: Our plastic surgery unit is focused primarily on autologous breast reconstruction and is part of an interdisciplinary breast center. We offer immediate breast reconstruction (IBR) with autologous tissue for patients with positive BRCA 1 and 2, ductal carcinoma in situ (DCIS), invasive cancer without margin problems to the skin, as well as to correct poor oncologic and aesthetic breast conserving therapy (BCT) outcomes. In the majority of cases we prefer an Immediate-DElayed AutoLogous (IDEAL) breast reconstruction concept with a two-stage procedure. RESULTS: Over the last 10 years we performed more than 1,600 breast reconstructions with free flaps, performing the deep inferior epigastric perforator (DIEP) flap as our first choice for autologous tissue. We recommend IDEAL breast reconstruction, however approximately 15% of our cases are immediate one stage conservative mastectomies and breast reconstruction with the DIEP flap. CONCLUSIONS: For immediate reconstruction, the aesthetic outcome should not take precedence over oncologic considerations. Immediate one-stage, breast reconstruction with autologous tissue can be offered to the suitable patients which is most likely a healthy women with a small-to medium sized non ptotic breast receiving a conservative mastectomy. In all other cases, we recommend an IDEAL breast reconstruction approach in order to achieve a final result that is both satisfyingly pleasing and oncologically safe. PMID- 26855906 TI - Anatomy of the nipple and breast ducts. AB - Over time, variations of mastectomy came up and started allowing the oncological safety and the possibility of an immediate breast reconstruction. Nipple sparing mastectomy (NSM) procedures have strongly increased in frequency and have become one of the best alternatives to treat breast cancer, also improving overall aesthetic outcomes and the achievement of contralateral breast symmetry. The nipple areola-complex (NAC) must be considered the identity of the breast concerning self-esteem of patients. This paper will remind the main anatomical topics around the nipple and breast ducts. PMID- 26855908 TI - Implant-based breast reconstruction following conservative mastectomy: one-stage vs. two-stage approach. AB - Conservative mastectomy with preservation of the nipple areolar complex is now considered a safe and effective technique in properly selected patients. Good candidates for this procedure include women with small to moderate breast volume having therapeutic or prophylactic mastectomy. Both autologous and prosthetic options are available; however prosthetic techniques are performed more frequently. Prosthetic approaches include immediate 1-stage (direct to implant) or 2-atge (tissue expander/implant) techniques. Delayed prosthetic reconstruction is also possible with conservative mastectomy. This manuscript will review the 1 stage and 2-stage methods with an emphasis on indication, surgical techniques, and outcomes. PMID- 26855907 TI - Oncologic safety of conservative mastectomy in the therapeutic setting. AB - Conservative mastectomy is a form of nipple-sparing mastectomy which is emerging as a surgical option for selected breast cancer patients. This technique differs from subcutaneous mastectomy which is well established as a technique for risk reduction but leaves behind a finite remnant of retro-areolar breast tissue. Clinical trials have confirmed the efficacy and safety of breast conservation therapy for smaller localised breast tumors whereby a variable amount of surrounding normal tissue is excised with administration of breast radiotherapy post-operatively. Conservative mastectomy aims to remove all breast tissue with dissection continued into the core of the nipple. However, the indication for conservative mastectomy remains to be defined but generally includes tumors of modest size located at least 2 cm away from the nipple. Patients undergoing conservative mastectomy do not necessarily receive adjuvant radiotherapy and this may only be intra-operative irradiation of the nipple-areola complex (NAC). Preservation of the NAC as part of a skin-sparing mastectomy in patients who might otherwise require standard mastectomy is of unproven safety from an oncologic perspective but is associated with enhanced cosmetic outcomes and quality-of-life. The advent of conservative mastectomy has coincided with a trend for "maximal surgery" with bilateral extirpation of all breast tissue in conjunction with immediate breast reconstruction. It is essential there is no compromise of local recurrence and survival in terms of ipsilateral breast cancer treatment. Further studies are required to clarify the indications for conservative mastectomy and confirm oncologic equivalence to either wide local excision and breast irradiation or conventional/skin-sparing mastectomy with sacrifice of the nipple areola complex. PMID- 26855909 TI - Conservative mastectomies for breast cancer and risk-reducing surgery: the Memorial Sloan Kettering Cancer Center experience. AB - Demand for conservative mastectomies continues to increase as more patients choose to undergo breast reconstruction, often with simultaneous contralateral prophylactic mastectomy (CPM). In addition, the increasing use of risk-reducing surgery in high-risk groups has contributed to the increased use of these techniques. We have reviewed the indications and outcomes of a large group of patients undergoing nipple-sparing mastectomy (NSM) at this institution. In total, 728 nipple-sparing mastectomies (NSMs) were performed in 413 patients between 2000 and 2013, for treatment of breast cancer (n=269) or risk reduction (n=459). Of 728 NSMs performed, 177 (24.3%) were in patients known to have a BRCA1 or BRCA2 germline mutation, or a genetic variant of uncertain significance. There was an incidental finding of ductal carcinoma in situ (DCIS) or invasive carcinoma in 22 (4.8%) and 8 (1.7%) of 459 prophylactic NSMs, respectively. In addition, unexpected invasive carcinoma was found in 17 of 98 therapeutic NSMs (17.3%) performed for DCIS. At median follow-up of 49 months, there were no known cases of local recurrence and only one case of regional recurrence. Immediate breast reconstruction was performed in 409 patients, most of whom underwent tissue expander/implant based procedures (n=401). Although 273 breasts (37.5%) had some evidence of skin desquamation at follow-up, most resolved spontaneously with 47 breasts (6.5%) requiring debridement. Other complications included hematoma in seven breasts (1%) and wound infection in 31 breasts (4.3%). Expander/implant removal was required in 20 cases (2.8%). The nipple-areola complex (NAC) was subsequently excised in 10 of 728 breasts (1.4%) due to oncologic concerns following assessment of retroareolar tissue. NSM was successful in most patients with an acceptable complication rate and in few patients subsequently undergoing removal of the NAC. Patients requiring mastectomy for breast cancer or risk reduction may now benefit from conservative mastectomy techniques such as NSM, resulting in improved cosmesis and, possibly, a reduced psychological impact. PMID- 26855910 TI - The use of postoperative radiation after nipple sparing mastectomy. AB - Nipple-sparing mastectomy (NSM) is a surgical procedure designed to reduce the disabling psychological effects of radical mastectomy. The preservation of the nipple-areola complex (NAC) produces a better result of the breast reconstruction, but some concerns exist of increasing the risk for local recurrence (LR). To reduce this risk a restricted inclusion criteria is suggested. In case of patients with high or intermediate risk the use of radiation therapy (RT) is also recommended, but a current standard for radiation after NSM is not available. In the literature, with few exceptions, there are few reports detailing indication and technique of radiation after NSM. There is a general consensus that post-mastectomy radiation therapy (PMRT) should be considered for patients with four or more positive axillary lymph nodes, primary tumour size 5 cm or more, T4 disease for skin involvement and positive margin. Almost all of these patients are candidate to receive external beam radiotherapy to the chest wall and to the supraclavicular/axillary region, less to the internal mammary chain. PMRT could be omitted in elderly patients with poor clinical conditions or co-morbidities that substantially reduce the life expectancy. Because the indications of NSM have been progressively extended also to larger or multi-centric tumours, this procedure has been criticised because of the increased risk of recurrence behind the areola due to the remaining glandular tissue, especially the terminal ducts, kept to preserve its blood supply, and especially in case of more advanced tumours. To reduce this concern, adjuvant RT after NSM should be administered in high risk patients who meet the criteria for current recommendations, but in other cases, such as in patients with intermediate risk or lower stage, the indication should be discussed on individual. PMID- 26855911 TI - Surgical decision making in conservative mastectomies. AB - We present some clinical advice to drive the decision process in performing conservative mastectomies. Several factors are taken into consideration to indicate these techniques. First of all, we need to identify patients who need a mastectomy due to the extension of the disease. In this case we suggest assessing patients anthropometric characteristics (breast volume-ptosis), and personal preferences regarding the extension of surgical treatment. Small, medium size, without ptosis or with moderate ptosis can be better served by standard nipple sparing mastectomy. Large and ptotic breast can be removed and reconstructed performing a skin-reducing mastectomy. Mastectomies cannot replace breast conservation and should be discouraged whenever breast-conserving surgery can be performed with good results. However, in some selected cases, and especially in patients with small breast, conservative mastectomies with contralateral reshape can yield favourable results. PMID- 26855912 TI - Oncoplastic techniques in breast surgery for special therapeutic problems. AB - Resection of large tumors can be challenging, from the view point of breast preservation. Oncoplastic techniques are a valuable component of breast surgery in patients with large breast tumors who desire breast preservation. These techniques have been shown to be oncologically safe, while maintaining acceptable breast cosmesis. For locally advanced or recurrent breast cancers, the goals of surgery include local disease control and palliation of clinical symptoms. Oncoplastic surgery is also effective and oncologically safe in these situations. The need to completely remove all foci of cancers with adequate surgical margins often requires the displacement of adjacent or distant skin and soft tissue to cover the resulting soft tissue defect. Sometimes doing so can be cosmetically pleasing as well. In this article we present three special therapeutic problems in three distinct conditions, all resolved with oncoplastic techniques: the benign breast condition, malignant breast condition, and the palliative setting. PMID- 26855913 TI - Arrowhead approach for malignancies in the lower hemisphere of the breast. AB - Breast conservation treatment (BCT) is the preferred modality of treatment for early breast cancer. However, a moderate proportion of women will develop deformity and those with tumours in the lower hemisphere of the breast pose a particular challenge. Here, a technique is described which allows acceptable cosmetic outcome in women with small or medium-sized breasts without the use of therapeutic mammoplasty or volume replacement with flaps. PMID- 26855914 TI - Sedation for Gastrointestinal Endoscopy: Practical Issues in Patient Safety and Quality Management. PMID- 26855915 TI - Obscure Gastrointestinal Bleeding: Capsule or Balloon? PMID- 26855916 TI - Can We Measure the Learning Curve of Colonoscopy Using Polyp Detection Rate? PMID- 26855917 TI - Current Status and Research into Overcoming Limitations of Capsule Endoscopy. AB - Endoscopic investigation has a critical role in the diagnosis and treatment of gastrointestinal (GI) diseases. Since 2001, capsule endoscopy (CE) has been available for small-bowel exploration and is under continuous development. During the past decade, CE has achieved impressive improvements in areas such as miniaturization, resolution, and battery life. As a result, CE is currently a first-line tool for the investigation of the small bowel in obscure gastrointestinal bleeding and is a useful alternative to wired enteroscopy. Nevertheless, CE still has several limitations, such as incomplete examination and limited diagnostic and therapeutic capabilities. To resolve these problems, many groups have suggested several models (e.g., controlled CO2 insufflation system, magnetic navigation system, mobile robotic platform, tagging and biopsy equipment, and targeted drug-delivery system), which are in development. In the near future, new technological advances will improve the capabilities of CE and broaden its spectrum of applications not only for the small bowel but also for the colon, stomach, and esophagus. The purpose of this review is to introduce the current status of CE and to review the ongoing development of solutions to address its limitations. PMID- 26855918 TI - The Role of Capsule Endoscopy in Patients with Obscure Gastrointestinal Bleeding. AB - Obscure gastrointestinal bleeding (OGIB) accounts for 5% of all gastrointestinal (GI) bleeding cases and is often caused by small bowel lesions. Capsule endoscopy (CE), which allows non-invasive visualization of the small bowel mucosa, has revolutionized the evaluation of OGIB. CE is preferred by both patients and physicians mainly because of its non-invasiveness, and is widely used as the first-line diagnostic modality for OGIB. The diagnostic yield of CE in OGIB has been reported to be in the range of 32% to 83%. Although no direct comparison has been made, a meta-analysis showed similar diagnostic yields between CE and double balloon enteroscopy (DBE) for OGIB. However, CE could enhance the yield of subsequent DBE and serve as a guide for optimizing the insertion route for DBE. Even after negative CE, selected patients could benefit from second-look CE for OGIB. In terms of outcomes, a favorable clinical impact after CE has been reported in several studies. However, observations indicate that CE might not influence clinical outcomes directly, but rather play a role in selecting patients with OGIB who are likely to benefit from subsequent evaluation and intervention. PMID- 26855919 TI - The Usefulness of Capsule Endoscopy for Small Bowel Tumors. AB - Video capsule endoscopy (VCE) has expanded the range of endoscopic examination of the small bowel. The clinical application of VCE is mainly for obscure gastrointestinal bleeding (OGIB) and small bowel tumor is one of the clinically significant diagnoses of VCE, often requiring subsequent invasive interventions. Small bowel tumors are detected with a frequency of around 4% with VCE in indications of OGIB, iron deficiency anemia, unexplained abdominal pain, and others. Protruding mass with bleeding, mucosal disruption, irregular surface, discolored area, and white villi are suggested as the VCE findings of small bowel tumor. Device assisted enteroscopy (DAE), computed tomography enteroclysis/enterography and magnetic resonance enteroclysis/enterography also have clinical value in small bowel examination and tumor detection, and they can be used with VCE, sequentially or complementarily. Familial adenomatous polyposis, Peutz-Jeghers syndrome, melanoma, lymphoma, and neuroendocrine tumor with hepatic metastasis are the high risk groups for small bowel tumors, and surveillance programs for small bowel tumors are needed. VCE and radiological imaging have value in screening, and in selected cases, DAE can provide more accurate diagnosis and endoscopic treatment. This review describes the usefulness and clinical impact of VCE on small bowel tumors. PMID- 26855920 TI - Challenges and Future of Wireless Capsule Endoscopy. AB - In 2015, capsule endoscopy was introduced as the main investigation method for small bowel mucosal diseases, and its role in colonic diseases has been gradually revealed. Future challenges for capsule endoscopy, besides improvements of image quality and visualization of each part of the small bowel and colonic mucosa, include the development of gastric capsules, the capacity to perform histological examination of the mucosa, and maybe in the future, some capsule endoscopy-driven therapeutics. The aim of this review was to evaluate the clinical demands and feasibility of achieving the aforementioned objectives. PMID- 26855921 TI - Novel Endoscopic Management of Obesity. AB - Endoscopic procedures have been well-documented in the obesity field, but have not yet reached a sufficient level of evidence as stand-alone methods for treating obesity. It is unclear if they should take over. Although expanding, the array of bariatric surgical techniques does not fully meet the current needs, and there are not enough resources for increasing surgery. Surgery is avoided by a majority of patients, so that less aggressive procedures are necessary. For the time being, relevant endoscopic methods include intra-gastric balloons, gastric partitioning (Endo-plication), and the metabolic field (Endo-barrier). Surgical novelties and basic research are also important contributors owing to their potential combination with endoscopy. Conditions have been listed for implementation of bariatric endoscopy, because innovation is risky, expensive, and faces ethical challenges. A scientific background is being built (e.g., hormonal studies). Some techniques require additional study, while others are not ready but should be priorities. Steps and goals include the search for conceptual similarities and the respect of an ethical frame. Minimally invasive bariatric techniques are not ready for prime time, but they are already being successful as re-do procedures. A time-frame for step-strategies can be defined, and more investments from the industry are mandatory. PMID- 26855922 TI - Application and Efficacy of Super-Magnifying Endoscopy for the Lower Intestinal Tract. AB - Endoscopy plays a significant role in the diagnosis, management, and surveillance of colorectal cancer (CRC) and inflammatory bowel diseases (IBDs). Moreover, magnifying endoscopy and image-enhanced endoscopy has a crucial role in the clinical setting. Recently, a super-magnifying endoscope has been developed, and two devices, confocal laser endomicroscopy (CLE) and an endocytoscopy system (ECS), which allow in vivo microscopic inspection of the microstructural mucosal features of the gastrointestinal tract, are currently available. Studies on the use of ECS in CRC were reported by a Japanese group. Additionally, a few studies on the use of ECS in IBD have been reported. CLE has been shown to be reliable in assessing the activity of the disease in IBDs in both ulcerative colitis and Crohn's disease. Various published studies evaluated the use of CLE during colonoscopy to distinguish colorectal polyp pathology and neoplasia. However, these studies are heterogeneous, and further evidence is necessary to confirm the efficacy of CLE. PMID- 26855923 TI - New Scopes, New Accessories, New Stents for Interventional Endoscopic Ultrasound. AB - Technological advances have rapidly expanded the therapeutic potential of endoscopic ultrasound (EUS). Innovations in stent technology; directed adjunctive therapy for pancreatic tumors, including radiofrequency ablation and fiducial marker placement; advanced imaging modalities, including needle-based confocal laser endomicroscopy; and new echoendoscopes, such as the forward-viewing linear echoendoscope, are emerging as safe and effective tools and devices for providing a broad range of treatments and therapies previously not thought possible. In this review, we summarize and discuss the new echoendoscopes, accessories, and stents for interventional EUS and highlight the recent literature on technical and therapeutic efficacy. The therapeutic role and indications for EUS are rapidly evolving well beyond its current limits as new EUS-specific designed tools are designed, and ultimately, should help achieve the goal of improving patient outcomes. PMID- 26855924 TI - Considerable Variability of Procedural Sedation and Analgesia Practices for Gastrointestinal Endoscopic Procedures in Europe. AB - BACKGROUND/AIMS: The use of moderate to deep sedation for gastrointestinal endoscopic procedures has increased in Europe considerably. Because this level of sedation is a risky medical procedure, a number of international guidelines have been developed. This survey aims to review if, and if so which, quality aspects have been included in new sedation practices when compared to traditional uncontrolled sedation practices. METHODS: A questionnaire was sent to the National Associations of Nurse Anesthetists in Europe and the National Delegates of the European Section and Board of Anaesthesiology from January 2012 to August 2012. RESULTS: Huge variation in practices for moderate to deep sedation were identified between and within European countries in terms of safety, type of practitioners, responsibilities, monitoring, informed consent, patient satisfaction, complication registration, and training requirements. Seventy-five percent of respondents were not familiar with international sedation guidelines. Safe sedation practices (mainly propofol-based moderate to deep sedation) are rapidly gaining popularity. CONCLUSIONS: The risky medical procedure of moderate to deep sedation has become common practice for gastrointestinal endoscopy. Safe sedation practices requiring adequate selection of patients, adequate monitoring, training of sedation practitioners, and adequate after-care, are gaining attention in a field that is in transition from uncontrolled sedation care to controlled sedation care. PMID- 26855925 TI - Roles of Capsule Endoscopy and Single-Balloon Enteroscopy in Diagnosing Unexplained Gastrointestinal Bleeding. AB - BACKGROUND/AIMS: The diagnostic algorithms used for selecting patients with obscure gastrointestinal bleeding (OGIB) for capsule endoscopy (CE) or balloon assisted enteroscopy (BE) vary among facilities. We aimed to demonstrate the appropriate selection criteria of CE and single balloon-assisted enteroscopy (SBE) for patients with OGIB according to their conditions, by retrospectively comparing the diagnostic performances of CE and BE for detecting the source of the OGIB. METHODS: We investigated 194 patients who underwent CE and/or BE. The rate of positive findings, details of the findings, accidental symptoms, and hemostasis methods were examined and analyzed. RESULTS: CE and SBE were performed in 103 and 91 patients, respectively, and 26 patients underwent both examinations. The rate of positive findings was significantly higher with SBE (73.6%) than with CE (47.5%, p<0.01). The rate of positive findings was higher in overt bleeding cases than in occult bleeding cases for both BE and SBE. Among the overt bleeding cases, the rate was significantly higher in ongoing bleeding cases than in previous bleeding cases. CONCLUSIONS: Both CE and SBE are useful to diagnose OGIB. For overt bleeding cases and ongoing bleeding cases, SBE may be more appropriate than CE because endoscopic diagnosis and treatment can be completed simultaneously. PMID- 26855926 TI - The Colonoscopist's Expertise Affects the Characteristics of Detected Polyps. AB - BACKGROUND/AIMS: The influence of the endoscopist on the polyp detection rate (PDR) is underappreciated in clinical practice. Moreover, flat lesions or lesions of the proximal colon are more difficult to detect. Here, we evaluated the differences in the PDR and the characteristics of detected polyps according to the experience of the colonoscopist. METHODS: We collected data on 2,549 patients who underwent screening colonoscopy performed by three fellows. The PDR was calculated according to the percentage of patients who had at least one polyp (method A) and according to the percentage of detected lesions (method B). The primary outcome included the change in the PDR, and the secondary outcome included the change in the characteristics of the detected polyps with increasing experience of the colonoscopist. RESULTS: No proportional correlation was found between the PDR and increasing experience in colonoscopy with method A; however, with method B, the PDR increased after 400 colonoscopies (p=0.0209). With method B, the detection rates of small polyps (<5 mm) (p=0.0015) and polyps in proximal sites (p=0.0050) increased after 300 colonoscopies. CONCLUSIONS: Our study demonstrated that the quality of a colonoscopy, measured by using the PDR, may increase when performed by experienced fellows. PMID- 26855927 TI - Increased Detection of Colorectal Polyps in Screening Colonoscopy Using High Definition i-SCAN Compared with Standard White Light. AB - BACKGROUND/AIMS: The aim of this study was to evaluate the efficacy of high definition (HD) i-SCAN for colorectal polyp detection in screening colonoscopy. METHODS: We retrospectively analyzed the records of 501 patients who had undergone screening colonoscopy performed by three endoscopists with either HD i SCAN (n=149) or standard white light (n=352) from January 2, 2014 through June 30, 2014. Patient information and inter-endoscopist variation as well as polyp number, endoscopic findings, and pathologic characteristics were reviewed. RESULTS: The detection rates of colorectal and neoplastic polyps were significantly higher using HD i-SCAN than standard white light colonoscopy (52% vs. 38.1%, p=0.004 for colorectal polyps; and 37.2% vs. 27.9%, p=0.041 for neoplastic polyps). Analysis of endoscopic findings revealed no difference in detected polyp size between HD i-SCAN and standard white light colonoscopy (4.59+/-2.35 mm vs. 4.82+/-2.81 mm, p=0.739), but non-protruding polyps were more commonly detected by i-SCAN than by standard white light colonoscopy (24.6% vs. 13.5%, p=0.007). CONCLUSIONS: Colonoscopy using HD i-SCAN had a significantly higher detection rate of colorectal polyps, including neoplastic polyps, because of improved sensitivity for detecting non-protruding lesions. PMID- 26855928 TI - Two Cases of Stress Cardiomyopathy during Esophagogastroduodenoscopy. AB - Esophagogastroduodenoscopy (EGD) is considered a relatively safe procedure. However, the procedure and the materials used in EGD with conscious sedation can cause stress to the patient. Adverse events during EGD have been reported, represented by cardiopulmonary complications. To date, five cases have reported worldwide to be associated with gastrointestinal endoscopy. Stress cardiomyopathy (SCMP) is a reversible cardiomyopathy that typically occurs in postmenopausal women due to stress and may resolve within a few weeks. SCMP resembles acute myocardial infarction but differs in terms of treatment and prognosis. Here, we describe two cases of SCMP with shock during EGD with conscious sedation. PMID- 26855929 TI - Communicating Tubular Esophageal Duplication Combined with Bronchoesophageal Fistula. AB - Esophageal duplication (ED) is rarely diagnosed in adults and is usually asymptomatic. Especially, ED that is connected to the esophagus through a tubular communication and combined with bronchoesophageal fistula (BEF) is extremely rare and has never been reported in the English literature. This condition is very difficult to diagnose. Although some combinations of several modalities, such as upper gastrointestinal endoscopy, esophagography, computed tomography, magnetic resonance imaging, and endoscopic ultrasonography, can be used for the diagnosis, the results might be inconclusive. Here, we report on a patient with communicating tubular ED that was incidentally diagnosed on the basis of endoscopy and esophagography during the postoperational evaluation of BEF. PMID- 26855930 TI - Endoscopic Submucosal Dissection of an Inverted Early Gastric Cancer-Forming False Gastric Diverticulum. AB - Endoscopic submucosal dissection (ESD) is a standard treatment for early gastric cancer (EGC) that does not have any risk of lymph node or distant metastases. Here, we report a case of EGC resembling a diverticulum. Diverticular formation makes it difficult for endoscopists to determine the depth of invasion and to subsequently perform ESD. Because the false diverticulum does not have a muscular layer, this lesion can be treated with ESD. Our case was successfully treated with ESD. After ESD, the EGC was confined to the submucosal layer without vertical and lateral margin involvement. This is the first case in which ESD was successfully performed for a case of EGC that coexisted with a false gastric diverticulum. An additional, larger study is needed to determine the efficacy of ESD in various types of EGC, such as a false gastric diverticulum. PMID- 26855931 TI - Multiple Polypoid Angiodysplasia with Obscure Overt Bleeding. AB - Angiodysplasia (AD) is increasingly being recognized as a major cause of gastrointestinal bleeding. Morphologically flat lesions are common types of AD, whereas the polypoid types are rare. We report a case of multiple polypoid AD in the small bowel causing severe anemia and requiring surgical treatment. A 60-year old male patient visited our hospital with dyspnea and hematochezia. He had a history of myocardial infarction and was taking both aspirin and clopidogrel. Capsule endoscopy, enteroscopy, computed tomography, and angiography revealed multifocal vascular lesions with a polypoid shape in the jejunum. Surgical resection was performed because endoscopic treatment was considered impossible with the number and the location of lesions. The risk of recurrent bleeding related to the use of antiplatelet agents also contributed to the decision to perform surgery. AD was histologically diagnosed from the surgical specimen. He resumed taking both aspirin and clopidogrel after surgery. He fully recovered and has been doing well during the several months of follow-up. PMID- 26855932 TI - Endoscopic Double Metallic Stenting in the Afferent and Efferent Loops for Malignant Afferent Loop Obstruction with Billroth II Anatomy. PMID- 26855933 TI - Erratum: An Ultrathin Endoscope with a 2.4-mm Working Channel Shortens the Esophagogastroduodenoscopy Time by Shortening the Suction Time. AB - [This corrects the article on p. 516 in vol. 48, PMID: 26668798.]. PMID- 26855934 TI - Research Question, Study Design and Continuous Research Education and Training Exercises (CREATE) Program. AB - The clinical research project starts with identifying the optimal research question, one that is ethical, impactful, feasible, scientifically sound, novel, relevant, and interesting. The project continues with the design of the study to answer the research question. Such design should be consistent with ethical and methodological principles, and make optimal use of resources in order to have the best chances of identifying a meaningful answer to the research question. Physicians and other healthcare providers are optimally positioned to identify meaningful research questions the answer to which could make significant impact on healthcare delivery. The typical medical education curriculum, however, lacks solid training in clinical research. We propose CREATE (Continuous Research Education And Training Exercises) as a peer- and group-based, interactive, analytical, customized, and accrediting program with didactic, training, mentoring, administrative, and professional support to enhance clinical research knowledge and skills among healthcare professionals, promote the generation of original research projects, increase the chances of their successful completion and potential for meaningful impact. The key features of the program are successive intra- and inter-group discussions and confrontational thematic challenges among participating peers aimed at capitalizing on the groups' collective knowledge, experience and skills, and combined intellectual processing capabilities to optimize choice of research project elements and stakeholder decision-making. PMID- 26855935 TI - Investigating Functional Impairment in Preclinical Alzheimer's Disease. PMID- 26855936 TI - Brain aerobic glycolysis functions and Alzheimer's disease. AB - Genetic, biochemical, pathological, and biomarker data demonstrate that Alzheimer's disease (AD) pathology, including the initiation and progressive buildup of insoluble forms of beta-amyloid (Abeta), appears to begin ~ 10-15 years prior to the onset of cognitive decline associated with AD. Metabolic dysfunction, a prominent feature of the evolving brain pathology, is reflected in a decline of total glucose utilization. Despite decades of interest in declining glucose use in AD no detailed consideration had been given to the possibility that this decline is not just a decline in energy consumption but rather in glycolysis alone. Glycolysis is a multi-step process that prepares the glucose molecule for oxidative phosphorylation and the generation of energy. In the normal brain, glycolysis exceeds that required for the needs of oxidative phosphorylation. Because it is occurring in a setting with adequate oxygen available for oxidative phosphorylation it is often referred to as aerobic glycolysis (AG). AG is a biomarker of a group of metabolic functions broadly supporting biosynthesis and neuroprotection. The distribution of AG in normal young adults correlates spatially with Abeta deposition in AD patients and cognitively normal individuals with elevated Abeta. In transgenic mice extracellular fluid Abeta and lactate, a marker of AG, vary in parallel regionally and with changes in activity. Reducing neuronal activity locally in transgenic mice attenuates plaque formation suggesting that plaque formation is an activity dependent process associated with aerobic glycolysis. PMID- 26855937 TI - A clinical evaluation of botulinum toxin-A injections in the temporomandibular disorder treatment. AB - BACKGROUND: This study clinically evaluated the effect of botulinum toxin type A (BTX-A) in the temporomandibular disorder (TMD) treatment using Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). METHODS: A total of 21 TMD patients were recruited to be treated with BTX-A injections on the bilateral masseter and temporalis muscles and were followed up by an oral and maxillofacial surgeon highly experienced in the TMD treatment. For each patient, diagnostic data gathering were conducted according to the RDC/TMD. Characteristic pain intensity, disability points, chronic pain grade, depression index, and grade of nonspecific physical symptoms were evaluated. Wilcoxon signed-rank test was applied for statistical analysis. RESULTS: The results showed that more than half of the participants (85.7 %) had parafunctional oral habits such as bruxism or clenching. In comparison between pre- and post-treatment results, graded pain score, characteristic pain intensity, disability points, chronic pain grade, and grade of nonspecific physical symptoms showed statistically significant differences after the BTX-A injection therapy (p < 0.05). Most patients experienced collective decrease in clinical manifestations of TMD including pain relief and improved masticatory functions after the treatment. CONCLUSIONS: Within the limitation of our study, BTX-A injections in masticatory musculatures of TMD patients could be considered as a useful option for controlling complex TMD and helping its associated symptoms. PMID- 26855938 TI - Cruciate retaining and cruciate substituting ultra-congruent insert. AB - The posterior cruciate ligament (PCL) conservation and the polyethylene insert constraint in total knee arthroplasty (TKA) are still debated. The PCL is one of the primary stabilizers of the joint, but cruciate retaining (CR) implants have the disadvantage of a difficult balancing of the PCL. Postero-stabilized (PS) implants were introduced to reduce this problem. However, also the PS implants have some disadvantages, due to the cam-mechanism, such as high risk of cam mechanism polyethylene wear. To minimize the polyethylene wear of the cam mechanism and the bone sacrifice due to the intercondylar box, different types of inserts were developed, trying to increase the implant conformity and to reduce stresses on the bone-implant interface. In this scenario ultra-congruent (UC) inserts were developed. Those inserts are characterized by a high anterior wall and a deep-dished plate. This conformation should guarantee a good stability without the posterior cam. Few studies on both kinematic and clinical outcomes of UC inserts are available. Clinical and radiological outcomes, as well as kinematic data are similar between UC mobile bearing (MB) and standard PS MB inserts at short to mid-term follow-up. In this manuscript biomechanics and clinical outcomes of UC inserts will be described, and they will be compared to standard PS or CR inserts. PMID- 26855939 TI - Rotational alignment of the tibial component in total knee arthroplasty. AB - Many surgical techniques, correlated to different anatomical landmarks, have been proposed to allow a satisfactory rotational alignment of the tibial component in primary total knee arthroplasty (TKA). Unfortunately, an accurate landmark has not yet been established although many computer models using CT reconstructions and standard radiologic studies have been performed. In this review article, the authors propose a new anatomical rotational reference for a correct positioning of the tibial component during primary TKA; the authors compared the results of their studies with the current literature on rotational alignment references and previously proposed surgical techniques. The authors also analyzed the correlation between classic and newer tibial baseplate designs and different tibial rotational landmarks. PMID- 26855940 TI - Rotational alignment of the femoral component in total knee arthroplasty. AB - We describe here various surgical options to obtain a correct rotational alignment of femoral component in total knee arthroplasty (TKA). The correct rotational alignment is the key point to obtain a rectangular balanced flexion gap as well to have a good patellar tracking. For that reason, rotation alignment largely affects postoperative kinematic results particularly during flexion. PMID- 26855941 TI - Bicompartmental knee arthroplasty. AB - Total knee arthroplasty (TKA) is the most worldwide practiced surgery for knee osteoarthritis and its efficacy is mightily described by literature. Concerns about the invasiveness of TKA let the introduction of segmental resurfacing of the joint for younger patients with localized osteoarthritis. Bone stock sparing and ligaments preservation are the essence of both unicompartmental knee arthroplasty (UKA) and bicompartmental knee arthroplasty (BKA). Advantages related to BKA are the respect of knee biomechanics, lower complications rates, shorter hospital stay, faster rehabilitation. Moreover, in case of failure of the first implant the conversion to TKA is undemanding and can be compared to a standard prosthesis. Our experience suggest that BKA is a reliable technique in selected cases and especially younger people with higher functional requests can favourably profit from it. Although those results are encouraging, we still need further prospective, randomized, long-term studies to finally assess BKA indications and outcomes. PMID- 26855942 TI - Medial pivot knee in primary total knee arthroplasty. AB - Total knee arthroplasty (TKA) with a medial pivot design was developed in order to mimic normal knee kinematics; the highly congruent medial compartment implant should improve clinical results and decrease contact stresses. Clinical and radiographic mid-term outcomes are satisfactory, but we need other studies to evaluate long-term results and indications for unusual cases. PMID- 26855943 TI - Evolution of trochlear compartment geometry in total knee arthroplasty. AB - BACKGROUND: The study aimed to compare trochlear profiles in recent total knee arthroplasty (TKA) models and to determine whether they feature improvements compared to their predecessors. The hypothesis was that recent TKA models have more anatomic trochlear compartments and would display no signs of trochlear dysplasia. METHODS: The authors analyzed the geometry of the 6 following TKA models using engineering software: PFC and Attune (DePuy), NexGen and Persona (Zimmer), Noetos and KneeTec (Tornier). The mediolateral trochlear profiles were plotted at various flexion angles (0 degrees , 15 degrees , 30 degrees and 45 degrees ) to deduce the sulcus angle. RESULTS: Analysis of sulcus angles reveals general convergence of recent designs towards anatomic values. At 0 degrees of flexion, sulcus angles of recent implant models were between 156.0-157.4 degrees , while those of previous generation models between 154.5-165.5 degrees . At 30 degrees of flexion, sulcus angles of recent models also lie within 145.7-148.6 degrees , but those of previous models are between 149.5-152.0 degrees . All three manufacturers deepened their trochlear profile at 30 degrees of flexion in recent models compared to earlier designs. Sulcus angles converge towards anatomic values but still exceed radiologic signs of dysplasia by 2-5 degrees . CONCLUSIONS: Recent TKA designs have more anatomic trochlear geometries than earlier TKA models by the same manufacturers, but trochlear compartments still exceed radiologic signs of trochlear dysplasia by 2 degrees to 5 degrees . The hypothesis that recent TKA models display no signs of trochlear dysplasia is therefore refuted. Surgeons should be aware of design limitations to optimize choice of implant and extensor mechanisms alignment. LEVEL OF EVIDENCE: IV geometric implant analysis. PMID- 26855944 TI - Effects of methylene blue in acute lung injury induced by oleic acid in rats. AB - BACKGROUND: In acute lung injury (ALI), rupture of the alveolar-capillary barrier determines the protein-rich fluid influx into alveolar spaces. Previous studies have reported that methylene blue (MB) attenuates such injuries. This investigation was carried out to study the MB effects in pulmonary capillary permeability. METHODS: Wistar rats were divided into five groups: (I) Sham: saline bolus; (II) MB, MB infusion for 2 h; (III) oleic acid (OA), OA bolus; (IV) MB/OA, MB infusion for 2 h, and at 5 min after from the beginning, concurrently with an OA bolus; and (V) OA/MB, OA bolus, and after 2 h, MB infusion for 2 h. After 4 h, blood, bronchoalveolar lavage (BAL), and lung tissue were collected from all groups for analysis of plasma and tissue nitric oxide, calculation of the wet weight to dry weight ratio (WW/DW), and histological examination of lung tissue. Statistical analysis was performed using nonparametric test. RESULTS: Although favourable trends have been observed for permeability improvement parameters (WW/WD and protein), the results were not statistically significant. However, histological analysis of lung tissue showed reduced lesion areas in both pre- and post-treatment groups. CONCLUSIONS: The data collected using this experimental model was favourable only through macroscopic and histological analysis. These observations are valid for both MB infusions before or after induction of ALI. PMID- 26855945 TI - Missing data imputation: focusing on single imputation. AB - Complete case analysis is widely used for handling missing data, and it is the default method in many statistical packages. However, this method may introduce bias and some useful information will be omitted from analysis. Therefore, many imputation methods are developed to make gap end. The present article focuses on single imputation. Imputations with mean, median and mode are simple but, like complete case analysis, can introduce bias on mean and deviation. Furthermore, they ignore relationship with other variables. Regression imputation can preserve relationship between missing values and other variables. There are many sophisticated methods exist to handle missing values in longitudinal data. This article focuses primarily on how to implement R code to perform single imputation, while avoiding complex mathematical calculations. PMID- 26855946 TI - Thoracoscopic left mediastinal lymph node dissection. AB - In Japan, the use of video-assisted thoracoscopic surgery (VATS) for primary lung cancer is increasing. However, it is not easy to perform mediastinal lymph node dissection using VATS as effectively as it is performed using thoracotomy. Herein, I have presented two techniques for subcarinal lymph node dissection from the left thoracic cavity: one involves the retraction of the lower bronchus towards the visceral and cranial side before inferior pulmonary vein resection to secure the view of the right lower portion. The other involves the separation of lymph nodes from the right main bronchus before separation from the left bronchus, to prevent the lymph nodes from falling down and interrupting the right side view. Moreover, I have also described a technique that facilitates left upper mediastinal lymph node dissection. It involves traction of a thoracic cardiac branch from the recurrent laryngeal nerve allowing visualization of the bottom of the #4L lymph node, so that it can be dissected easily. There has been no observation of recurrent nerve paralysis using this procedure. PMID- 26855947 TI - Childhood colon cancer in a patient with ataxia telangiectasia. AB - BACKGROUND: Ataxia-telangiectasia (AT) is a rare autosomal recessive disease characterized by progressive neurologic impairment and cerebellar ataxia. In addition, patients with this disease are known to have an inherent increased susceptibility to the development of cancer, predominantly hematologic malignancies. METHODS: We report the case of a young boy with AT from Russia, who had abdominal pain. Laboratory tests and radiologic examinations were performed to him. RESULTS: After abdominal computed tomography (CT), colonoscopy and surgical interventions, the young boy was diagnosed with colon cancer that had signet ring cell features. CONCLUSIONS: It is known that the patient with AT appeared to be predisposed to various tumors, including leukemia or lymphoma, which are more common in childhood. Even if the patient with AT could have solid tumor such as stomach cancer or breast cancer, it is less likely to have colon cancer, especially signet ring cell type. Actually, no case of colon cancer has ever been reported, especially in young patient and hence, we have focused on this point and are hereby reporting this unique case. PMID- 26855948 TI - A multifunctional bispecific antibody against Pseudomonas aeruginosa as a potential therapeutic strategy. PMID- 26855949 TI - Smart CARS: optimized development of a chimeric antigen receptor (CAR) T cell targeting epidermal growth factor receptor variant III (EGFRvIII) for glioblastoma. PMID- 26855950 TI - Improved survival with the addition of radiotherapy to androgen deprivation: questions answered and a review of current controversies in radiotherapy for non metastatic prostate cancer. AB - The contemporary standard of care for locally advanced high-risk prostate cancer includes a combination of dose-escalated radiotherapy (RT) plus androgen deprivation therapy (ADT). However, 20 years ago, at the inception of the National Cancer Institute of Canada (NCIC) led study (NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110), the survival impact of prostate RT for high-risk disease was uncertain. Recently, Mason, Warde and colleagues presented the final results of this NCIC/MRC study (PMID: 25691677) randomizing 1,205 high-risk prostate cancer patients to ADT + RT vs. ADT alone. These updated results confirm substantial improvements with the addition of RT to ADT for the endpoints of overall survival (OS), disease-free survival (DFS), and biochemical recurrence. Close examination of subtleties of this trial's design highlight some of the most salient controversies in the field of prostate RT, including the risk-stratified roles of ADT, optimal ADT duration, and RT field design in the dose-escalated and intensity-modulated radiotherapy (IMRT) era. PMID- 26855951 TI - One more role for the gut: microbiota and blood brain barrier. PMID- 26855952 TI - Predominant histologic subtype in lung adenocarcinoma predicts benefit from adjuvant chemotherapy in completely resected patients: discovery of a holy grail? AB - The recently published 2015 World Health Organisation (WHO) classification of lung tumors, which is based on the 2011 International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ATS) multidisciplinary classification, recommends diagnosis of resected lung adenocarcinoma according to the predominant histologic subtype. This has been shown to correlate with overall and disease-free survival (DFS) in many studies from four continents. Now classification according to predominant histologic subtype has been demonstrated to predict benefit from adjuvant chemotherapy in a subset of patients with completely resected lung adenocarcinoma previously included in the International Adjuvant Lung Cancer Trial (IALT), JBR.10, Cancer and Leukemia Group B (CALGB) 9633 and Adjuvant Navelbine International Trialist Association 01 (ANITA) adjuvant chemotherapy trials, all of which were part of the LACE-Bio study. This "hot-off-the press" landmark investigation further cements the clinical importance of classification of resected lung adenocarcinoma according to predominant histologic subtype and suggests that it could be a critical factor for patient stratification in future clinical trials. PMID- 26855953 TI - Intraoperative mechanical ventilation in patients with non-injured lungs: time to talk about tailored protective ventilation? PMID- 26855954 TI - Management of patients with chest pain presenting to the emergency department: in need for the implementation of the 1 h rapid rule-out algorithm using high sensitivity troponin I assays in clinical practice. PMID- 26855955 TI - Infectious aortitis or acute aortic syndrome-that is the question. PMID- 26855956 TI - No association between birth season and vitamin D concentration in adults in a North Norwegian population-the Tromso study. PMID- 26855957 TI - The impact of seasonality and other determinants on vitamin D concentration in childhood and adulthood: still an unresolved issue. PMID- 26855958 TI - Trials are not for the benefit of patients. PMID- 26855959 TI - Erratum to muscle pathology, limb strength, walking gait, respiratory function and neurological impairment establish disease progression in the p.N155K canine model of X-linked myotubular myopathy. AB - [This corrects the article on p. 262 in vol. 3, PMID: 26605308.]. PMID- 26855960 TI - Extent of Use of Aloe vera Locally Extracted Products for Management of Ailments in Communities of Kitagata Sub-county in Sheema District, Western Uganda. AB - Aloe vera is widely used locally in communities in Uganda as a medicinal plant. It is said to contain various nutrient substances and vitamins that have curative properties. It is said to heal a variety of diseases in various communities. However the extent of use of this potential medicinal plant in Uganda and the various ailments for which it is used and the treatment outcomes are not clearly established and documented. In this cross-sectional study, carried out in August 2012 in Kitagata sub-county in Sheema district in western Uganda, data was collected from 131 randomly selected adult respondents using an interviewer administered semi-structured questionnaire. Key informants interviews and focused group discussions were also carried out with purposively selected participants. Data were collected on social demographic characteristics, practices and beliefs about Aloe vera. The data were analyzed using Excel version 2007 and Epi_Info software. To get the proportion of the community that use Aloe vera, the number of respondents that use aloe vera was expressed as a percentage of the total number of respondents. It was found out that all the respondents (100%) know aloe vera plant, 96.1% think that it can cure and 84.7% have ever used it. 90.9% of the respondents believe that Aloe vera is effective in curing ailments. 82.9% of these strongly believe in Aloe vera's effectiveness. The diseases reported included malaria (31%), wounds (23%), abdominal pains (16%) and skin diseases (9%) among others. It was significantly noted that all the participants who had ever used Aloe vera still believe in it. 92.0% respondents reported that they can recommend aloe vera to a friend or relative. Only one participant strongly disagrees that Aloe vera has any curative properties and has never used it. PMID- 26855961 TI - Pattern of anti-diabetic drugs prescribed in a tertiary care hospital of Bangladesh. AB - BACKGROUND: Globally, diabetes mellitus is a common endocrine disorder. This study was conducted for collecting the demographic details of diabetic patients and determining the pattern of drugs prescribed among them in outpatient department of a tertiary healthcare center. METHODS: A descriptive type of cross sectional study was carried out at the outpatient department of Endocrinology, Dhaka Medical College Hospital, Bangladesh from 1 May to 31 July, 2015. Diabetic patients receiving the management for at least 6 months were enrolled and interviewed by the researchers after getting informed written consent. Structured case record form was used for demographic data & prescription details. Data were analysed using computer in SPSS 22 and Microsoft Excel 2010. RESULTS: Altogether 105 patients, 40 males (38.1%) and 65 females (61.9%) were enrolled with urban predominance (69.5%) where 51 (48.6%) were in the age group 47-61 years with a mean of 53.4 (SD+/-10.6) years. 70 (66.7%) had diabetic history of less than 5 years and 66 (62.9%) had at least one concurrent illness. Hypertension accounted for majority (34.3%) of complications. On an average, 5.62 (SD+/-3.16) drugs were advised per prescription for diabetes as well as associated co-morbidities and majority (23.8%) had 4 drugs. The majority of drugs (74.3%) were from local manufacturers. Most patients (62.9%) were prescribed with oral drugs singly. Metformin alone predominated in 41% prescriptions followed by the combination of Metformin and Sitagliptin (31.4%). CONCLUSIONS: The findings can serve as a guide to choose the formulation and combination of anti-diabetic drugs in this part of the world before developing & marketing any new drug. PMID- 26855963 TI - In adult smokers unwilling or unable to quit, does changing from tobacco cigarettes to electronic cigarettes decrease the incidence of negative health effects associated with smoking tobacco? A Clin-IQ. AB - Data from a randomized controlled trial and systematic review support the claim that switching from tobacco cigarettes to electronic cigarettes (e-cigarettes) can reduce the short-term negative health effects of smoking. In adult smokers unwilling or unable to quit, exhaled carbon monoxide levels, total number of cigarettes smoked, and exposure to nitrosamine chemicals were reduced within a 12 month period. While the electronic cigarette industry remains largely unregulated thus far, these studies provide encouraging hope in the uphill battle toward helping patients make informed and healthy choices. PMID- 26855964 TI - Coupling of HIV-1 gp120-derived Core Protein to Paramagnetic Beads and Adsorption Assays. AB - Analysis of the functional activity in polyclonal serum following immunization of a complex protein or glycoprotein immunogen is a very important but tedious process. Fine mapping of epitope specific antibodies is difficult when they are elicited at relatively low levels. In our recent study focused at developing an HIV-1 vaccine, we immunized rabbits with hyperglycosylated stable core immunogens, which were designed using high resolution structural information to elicit antibodies against the primary receptor-binding, CD4-binding site on HIV-1 gp120. Using a solid phase adsorption assay, we could map the serum antibodies to the conserved CD4-binding site, a known broadly neutralizing determinant on exterior envelope glycoprotein, gp120. PMID- 26855965 TI - Kinetic Analysis of Monoclonal Antibody Binding to HIV-1 gp120-derived Hyperglycosylated Cores. AB - Kinetic analysis of antibodies is one of the important study for characterization of antibodies and screening of ligands. In our recent study1, we compared the antigenic profiles and binding characteristics of four HIV-1 envelope glycoprotein (Env) core immunogens using multiple monoclonal antibodies by Bio Layer Light Interferometry (BLI). This technology enables real-time analysis of interactions on the surface of a fiber optic biosensor by accurately measuring kinetic constants such as Ka, Kd, and KD in a 96-well format. PMID- 26855966 TI - Comparison of Direct and Indirect Measures of E-cigarette Risk Perceptions. AB - OBJECTIVES: Risk perception measures of tobacco products relative to cigarettes are commonly used and important to tobacco research given that they may be associated with and predict tobacco use. However, results may differ based on measures used. This study compares direct and indirect approaches to measuring e cigarette/cigarette risk perceptions. METHODS: We compared the responses of 519 current smokers on a nationally representative 2014 survey that gauged perceptions of e-cigarettes' harm relative to cigarettes in two ways: 1) a single item direct measure of comparative harm and a two-item indirect measure (which measured perceived levels of harm from e-cigarettes and cigarettes independently in two parallel questions). RESULTS: We found that 60% of smokers rated e cigarettes "less harmful" than cigarettes when using a direct comparative risk measure versus 73% when using an indirect measure. Agreement between measure types was fair (Cohen's Kappa=0.45) and was lower for males, Blacks, older and less educated smokers. CONCLUSIONS: E-cigarettes were more likely to be rated by smokers as less harmful than cigarettes when using indirect versus direct measures. Additional methodology research into this area is warranted given the importance of risk perceptions to tobacco control interventions, communications, policy-making and regulation. PMID- 26855968 TI - Multivariate Granger Causality Analysis of Obesity Related Variables. AB - Obesity is a complex health outcome that is a combination of multiple health indicators. Here we attempt to explore the dependence network among multiple aspects of obesity. Two longitudinal cohort studies across multiple decades have been used. The concept of causality is defined similar to Granger causality among multiple time series, however, modified to accommodate multivariate time series as the nodes of the network. Our analysis reveals relatively central position of physical measurements and blood chemistry measures in the overall network across both genders. Also there are some patterns specific to only male or female population. The geometry of the causality network is expected to help in our strategy to control the increasing trend of obesity rate. PMID- 26855967 TI - Enterohemorrhagic Escherichia coli reduce mucus and intermicrovillar bridges in human stem cell-derived colonoids. AB - BACKGROUND AND AIMS: Enterohemorrhagic E. coli (EHEC) causes over 70,000 episodes of foodborne diarrhea annually in the USA. The early sequence of events which precede life-threatening hemorrhagic colitis and hemolytic uremic syndrome are not fully understood due to the initial asymptomatic phase of the disease and the lack of a suitable animal model. The aim of this study was to determine the initial molecular events in the interaction between EHEC and human colonic epithelium. METHODS: Human colonoids derived from adult proximal colonic stem cells were developed into monolayers to study EHEC-epithelial interactions. Monolayer confluency and differentiation were monitored by transepithelial electrical resistance (TER) measurements. The monolayers were apically infected with EHEC and the progression of epithelial damage over time was assessed using biochemical and imaging approaches. RESULTS: Human colonoid cultures recapitulate the differential protein expression patterns characteristic of the crypt and surface colonocytes. Mucus-producing differentiated colonoid monolayers are preferentially colonized by EHEC. Upon colonization, EHEC forms characteristic attaching and effacing lesions on the apical surface of colonoid monolayers. Mucin 2, a main component of colonic mucus, and protocadherin 24 (PCDH24), a microvillar resident protein, are targeted by EHEC at early stages of infection. The EHEC secreted serine protease, EspP, initiates brush border damage through PCDH24 reduction. CONCLUSIONS: Human colonoid monolayers are a relevant pathophysiological model which allows the study of early molecular events during enteric infections. Colonoid monolayers provide access to both apical and basolateral surfaces, thus providing an advantage over 3D cultures to study host pathogen interactions in a controllable and tractable manner. EHEC reduces colonic mucus and affects the brush border cytoskeleton in the absence of commensal bacteria. PMID- 26855969 TI - Recruitment, Follow-Up and Characteristics of HIV Infected Adults who Use Illicit Drugs in Southern Africa. AB - BACKGROUND: With one of the worst HIV prevalence rates in the world, Botswana has made great strides in addressing AIDS. Nevertheless, to fully contain the epidemic, outreach to marginalized groups, including illicit drug users, is critical. OBJECTIVE: To conduct targeted outreach within an intervention trial to recruit HIV-infected drug users and assess HIV disease and nutritional status. METHOD: Recruitment strategies included safeguarding confidentiality, involving ocal health-care professionals, advertising, and participation incentives. Urine toxicology, CD4 cell count, HIV viral load, blood chemistry, plasma micronutrients, dietary history, drug use and morbidity were assessed for two years. RESULTS: Targeted outreach identified 138 HIV-infected persons who used marijuana; 18.1% had CD4 cell counts <= 350 cells/MUL and 39.9% had low BMI. Eligible marijuana users (N=52) had significantly lower BMI (21.8 3.7 vs. 24.3 +/ 5.3 kg/m2, P=0.001), higher HIV viral load (4.36 +/- 0.89 vs. 4.09 +/- 0.89 log10, P=0.018), and higher kilocalorie intake (1924 +/- 1055 vs. 1620 +/- 926 Kcalories, P=0.025) than those who did not use marijuana (N=748) with similar CD4 cell count. Marijuana users >= 40 years old had more opportunistic diseases (P=0.020) than non-users of the same age. Benzodiazepine use was detected among 57 participants and they had higher BMI than marijuana users (24.4 +/- 6.8 vs. 21.8 +/- 3.7 kg/m2, P= 0.017). CONCLUSION: A population stigmatized by illicit drug use and HIV-infection can be brought into a clinical research setting in Africa. HIV-infected marijuana users were at a risk for higher HIV viral load, lower BMI and more comorbidities than nonusers. Outreach to this marginalized group is important for containing the HIV epidemic. PMID- 26855970 TI - U0126, an Inhibitor of MEK1/2, Increases Tumor Necrosis Factor-alpha-Induced Apoptosis, but not Interleukin-6 Induced Apoptosis in C-28/I2 Human Chondrocytes. AB - BACKGROUND: Activation of the SAPK/MAPK signaling pathway by pro-inflammatory cytokines is known to induce apoptosis in cultured articular chondrocytes. C 28/I2, an immortalized human juvenile chondrocyte cell line was employed to determine the extent to which recombinant human (rh) forms of the pro inflammatory cytokines, tumor necrosis factor-alpha (rhTNF-alpha,), interleukin-6 (rhIL-6) and oncostatin M (rhOSM) induced apoptosis. METHODS: The induction of apoptosis in the presence or absence of these cytokines was measured by the DAPI/TUNEL assay, by whether or not pro-caspase-3 was activated and by the extent to which poly-ADP-ribose polymerase (PARP) was degraded. FINDINGS: Only rhTNF alpha, and rhIL-6 significantly increased apoptosis in C-28/I2 chondrocytes, although rhOSM exhibited a strong trend (p=0.067) towards increasing the frequency of apoptotic chondrocytes. The number of apoptotic C28/I2 chondrocytes was significantly increased (p=1.3 * 10-5) by the combination of rhTNF-alpha and U0126 (10 MUM) compared to rhTNF-alpha alone. However apoptosis was not further increased by combining rhIL-6 with U0126. The LI-COR(r) western blot system showed that U0126 (10 MUM) inhibited the phosphorylation of extracellular signal regulated kinase-2 (p-ERK2) by phorbol myristate acetate-treated immortalized myometrial cells, U0126 (10 MUM) did not alter total U-ERK2. Western blot analysis also revealed that the increased frequency of apoptotic C-28/I2 chondrocytes induced by rhTNF-alpha and rhOSM, but not rhIL-6, was associated with PARP degradation. However, none of the cytokines resulted in pro-caspase-3 activation. CONCLUSION: These results showed that rhTNF-alpha and rhIL-6 were strong inducers of apoptosis in the immortalized C-28/I2 human chondrocyte cell line. They also suggested that inhibiting ERK2 phosphorylation via U0126-mediated inhibition of MEK1/2 activity, increased rhTNF-alpha-induced C-28/I2 chondrocyte apoptosis. PMID- 26855971 TI - Deep sequencing of HIV-1 variants from paired plasma and cerebrospinal fluid during primary HIV infection. AB - BACKGROUND: Limited data exist comparing viral quasispecies between cerebrospinal fluid (CSF) and plasma compartments during primary HIV infection. Deep sequencing is a new method to examine the HIV plasma and CSF quasispecies. METHODS: In this pilot study, deep sequencing of protease (PR) and reverse transcriptase (RT) was performed in plasma and CSF from participants during primary HIV infection. Estimated mutational load was calculated by mutant variant frequency multiplied by HIV-RNA level. RESULTS: Paired plasma and CSF samples were studied from five antiretroviral therapy-naive male participants with median 109 days post estimated transmission, age 32 years, CD4 cell count 580 cells/MUL, HIV-RNA 5.18 log10 copies/mL in plasma and 3.67 log10 copies/mL in CSF. Plasma samples averaged 7,124 reads of PR and 2,448 reads of RT, whereas CSF samples averaged 7,082 and 2,792 reads, respectively. A distinct drug-resistance pattern with linked mutations present at significant levels (5-10%) was detected in one participant in CSF. Other low abundance variants (>0.2%) were detected in plasma and CSF of four out of five participants. CONCLUSIONS: Deep sequencing of CSF HIV is technically possible with sufficient HIV-RNA levels. Differences between the quasispecies in the two compartments detected in one participant, which were present with a high mutational load in CSF at an estimated 3.6 months after HIV infection, suggest that early CNS compartmentalisation may be revealed by sensitive deep-sequencing methods. The presence of distinct low abundance (<1%) resistance variants in plasma and CSF of three other subjects may be significant, but further investigation is needed. PMID- 26855974 TI - Finding Disseration RAs within a PhD Student's Budget. AB - Participant recruitment can be a challenge to researchers, especially for those with limited resources and time. Doctoral students may need research assistants to recruit participants and complete data collection in a timely manner, but lack the experience and skills to find appropriate help for hire. By working closely with an adviser or mentor, doctoral students can successfully hire and lead a team of research assistants. This article provides concrete tips for doctoral students when hiring research assistants, and perspectives from a doctoral mentor student dyad. PMID- 26855972 TI - Towards a scalable HIV cure research agenda: the role of co-infections. AB - The development of a cure is among the foremost contemporary priorities in the field of HIV research. The science that underpins a potential HIV cure should be generalisable to the many millions of persons globally who enter antiretroviral treatment programs with advanced immunosuppression and/or an opportunistic infection. We provide five key suggestions for incorporation into the HIV cure research agenda to maximise the generalisability and applicability of an HIV cure once developed. PMID- 26855973 TI - Diabetic Lactoferrin Deficient Mice Demonstrates Greater Susceptibility to Experimental Periodontal Disease. AB - The objective of this study is to detrmine whether alloxan-induced diabetic Lactoferrin knockout (LFKO-/-) mice are more susceptible to periodontal disease caused by Aggregatibacter actinomycetemcomitans compared to the diabetic wild type (WT) mice. Diabetes was induced in mice by a single dose of alloxan (60 mg/kg) injected intravenously. Mice were categorized as diabetic when blood glucose levels >250 mg/dL were measured on the 7th day after the injection. Periodontal disease was experimentally induced by A. actinomycetemcomitans infection in alloxan induced diabetic WT and LFKO-/- mice. Fasting blood glucose levels and body weight were monitored throughout the study. At the end of the 12th week of infection, mice were sacrificed and bone loss among the groups was estimated by measuring the distance between cemento-enamel junction (CEJ) to the alveolar bone crest (ABC) at 12 sites on the molars. A. actinomycetemcomitans infected mice groups developed more alveolar bone loss than sham-infected animals. Diabetic LFKO-/- infected mice exhibited significant bone loss (P<0.01) and a higher mean fasting blood glucose level (P<0.05) when compared to diabetic WT infected mice. No statistically significant difference in fasting blood glucose level was found between the infected and sham-infected groups. Peripheral blood analysis at the end of the 12th week revealed a significant reduction in the platelet counts in LFKO-/- mice when compared to WT mice. Furthermore, diabetic LFKO-/- presented with lower counts than non-diabetic LFKO-/- mice (P<0.01). In conclusion, diabetic lactoferrin deficient mice are at a higher risk of developing periodontal infection induced by A. actinomycetemcomitans when compared to diabetic WTI mice. PMID- 26855975 TI - Qualitative Contributions to a Randomized Controlled Trial Addressing HIV/AIDS Stigma in Medical Students. AB - Specialized training for healthcare professionals (HCP) in order to reduce HIV/AIDS related stigma must be part of a public health model for HIV/AIDS. Tested interventions to reduce HIV/AIDS related stigma among HCP have been mostly absent from these efforts. A qualitative approach was used to assess stigma reduction within a traditional randomized controlled design in order to better understand how our current stigma intervention worked and was understood by 2nd year medical students. After conducting a quantitative follow up survey one-year post intervention we conducted 20 in-depth qualitative interviews with a subsample of our intervention group participants as part of the overall evaluation process. Once the interviews were finished, we transcribed them and used NVivo (v.8) to organized the qualitative data. In the process of analyzing the qualitative data we identified core intervention areas participants described as useful for their training and development: (1) acquiring more HIV/AIDS-related knowledge, (2) increased skills for management of high stigma situations, and (3) the ability to identify socio-structural factors that foster HIV infection among clients. The gathered information is important in order to have a deep understanding of how attitudinal change happens as part of our intervention strategies. PMID- 26855977 TI - Predicting Activation Across Individuals with Resting-State Functional Connectivity Based Multi-Atlas Label Fusion. AB - The alignment of brain imaging data for functional neuroimaging studies is challenging due to the discrepancy between correspondence of morphology, and equivalence of functional role. In this paper we map functional activation areas across individuals by a multi-atlas label fusion algorithm in a functional space. We learn the manifold of resting-state fMRI signals in each individual, and perform manifold alignment in an embedding space. We then transfer activation predictions from a source population to a target subject via multi-atlas label fusion. The cost function is derived from the aligned manifolds, so that the resulting correspondences are derived based on the similarity of intrinsic connectivity architecture. Experiments show that the resulting label fusion predicts activation evoked by various experiment conditions with higher accuracy than relying on morphological alignment. Interestingly, the distribution of this gain is distributed heterogeneously across the cortex, and across tasks. This offers insights into the relationship between intrinsic connectivity, morphology and task activation. Practically, the mechanism can serve as prior, and provides an avenue to infer task-related activation in individuals for whom only resting data is available. PMID- 26855976 TI - High Performance DNA Probes for Perinatal Detection of Numerical Chromosome Aberrations. AB - Human reproduction is a tightly controlled process of stepwise evolution with multiple, mostly yet unknown milestones and checkpoints. Healthy halpoid gametes have to be produced by the parents, which will fuse to form the diploid zygote that implants in the female uterus and grows to become first an embryo, then a fetus and finally matures into a newborn. There are several known risk factors that interfere with normal production of gametes, spermatocytes or oocytes, and often cause embryonic mortality and fetal demise at an early stage. Yet some embryos with chomosomal abnormalities can develop beyond the critical first trimester of pregnancy and, while those with supernumary chromosomes in their hyperdiploid cells will be spontaneously aborted, a small fraction of fetuses with an extra chromosome continues to grow to term and will be delivered as a liveborn baby. While minor clinical symptoms displayed by children with trisomies are manageable for many parents, the burden of caring for a child with numerical chromosome abnormalities can be overwhelming to partners or individual families. It also poses a significant financial burden to the society and poses ethical dilemma. In this communication, we will review the progress that has been made in the development of molecular techniques to test individual fetal cells for chromosomal imbalances. We will focus our discussion on the direct visualization of chromosome-specific DNA sequences in live or fixed specimens using fluorescence in situ hybridization (FISH) and, more specifically, talk about the groundbreaking progress that in recent years has been achieved towards an improved diagnosis with novel, chromosome-specific DNA probes. PMID- 26855978 TI - Predictive Modeling of Anatomy with Genetic and Clinical Data. AB - We present a semi-parametric generative model for predicting anatomy of a patient in subsequent scans following a single baseline image. Such predictive modeling promises to facilitate novel analyses in both voxel-level studies and longitudinal biomarker evaluation. We capture anatomical change through a combination of population-wide regression and a non-parametric model of the subject's health based on individual genetic and clinical indicators. In contrast to classical correlation and longitudinal analysis, we focus on predicting new observations from a single subject observation. We demonstrate prediction of follow-up anatomical scans in the ADNI cohort, and illustrate a novel analysis approach that compares a patient's scans to the predicted subject-specific healthy anatomical trajectory. PMID- 26855979 TI - The issue of (maybe) treating too much. PMID- 26855980 TI - Quetiapine's effect on the SCL-90-R domains in patients with borderline personality disorder. AB - BACKGROUND: This study aimed to examine the impact of quetiapine on the symptom and distress domains measured by the Symptom Checklist-90-Revised (SCL-90-R) in patients with borderline personality disorder (BPD). METHODS: Ninety-five participants meeting DSM-IV diagnostic criteria for BPD were randomly assigned to low-dosage (quetiapine, 150 mg/d; n = 33), moderate-dosage (quetiapine, 300 mg/d; n = 33), or placebo (n = 29). SCL-90-R was administered weekly over the course of an 8-week double-blind treatment phase. We used a mixed-effects model to analyze subscale scores of the SCL-90-R. RESULTS: Results showed that both dosages of quetiapine were effective in reducing levels of overall psychological distress, interpersonal sensitivity, depression, and hostility compared with those who received placebo. CONCLUSIONS: SCL-90-R can be a useful tool that would allow clinicians to collect information in addition to the DSM symptoms to better understand the diagnostic heterogeneity found in patients diagnosed with BPD. PMID- 26855981 TI - Pathological laughter and crying: A case series and proposal for a new classification. AB - BACKGROUND: Disorders of laughter and crying (DLC) are seen in several neuropsychiatric conditions. Their nomenclature remains under debate. METHODS: We present the clinical and imaging findings of 17 patients with DLC and introduce a new classification based on phenomenology and pathogenesis. According to intensity and frequency of laughter and crying (observed behavioral output), patients were divided into hypoactive or hyperactive DLC and subdivided into 5 subtypes: sensory (positive and negative), motor (positive and negative), and mixed. The sensory subtype is represented by disorders of "feeling processing," whereas the motor subtype is represented by disorders of "emotion processing." "Positive" and "negative" describe elicitation by irritative vs destructive lesions, respectively. RESULTS: Among the patients studied, DLC resulted from ischemic stroke (n = 12), intracerebral hemorrhage (n = 2), gunshot wound (n = 1), amyotrophic lateral sclerosis (n = 1), or vestibular migraine (n = 1). Ten patients had lesions in the brainstem, 4 in the cerebral hemispheres, and 2 in sub-cortical-diencephalic structures. Six patients had negative motor DLC, 5 had positive sensory DLC, 4 had negative sensory DLC, and 2 had positive motor DLC. Phenomenology changed or progressed to mixed DLC in 7 patients. CONCLUSIONS: This novel phenomenological and pathomechanistic nomenclature explains all subtypes of DLC in neurologic, medical, and psychiatric conditions. Future studies are needed to validate it prospectively. PMID- 26855982 TI - Psychiatric disorders after terrorist bombings among rescue workers and bombing survivors in Nairobi and rescue workers in Oklahoma City. AB - BACKGROUND: To examine the prevalence of psychopathology in 52 male rescue workers responding to the 1998 U.S. Embassy bombing in Nairobi, Kenya, comparing them with 176 male rescue workers responding to the 1995 Oklahoma City, Oklahoma, bombing and with 105 directly exposed male civilian survivors of the Nairobi bombing. METHODS: The Diagnostic Interview Schedule/Disaster Supplement assessed pre-disaster and post-disaster psychiatric disorders and variables related to demographics, exposure, disaster perceptions, and coping in all 3 disaster subgroups. RESULTS: The most prevalent post-disaster disorders were posttraumatic stress disorder (PTSD) (22%) and major depressive disorder (MDD) (27%) among Nairobi rescue workers, which were more than 2 and 4 times higher, respectively, than among Oklahoma City rescue workers. Alcohol use disorder was the most prevalent pre- and post-disaster disorder among Oklahoma City rescue workers. Nairobi rescue workers had a prevalence of PTSD and MDD not significantly different from Nairobi civilian survivors. CONCLUSIONS: Nairobi rescue workers were more symptomatic than Oklahoma City rescue workers and were as symptomatic as Nairobi civilian survivors. The vulnerability of Nairobi rescue workers to psychological sequelae may be a reflection of their volunteer, rather than professional, status. These findings contribute to understanding rescue worker mental health, especially among volunteer rescue workers, with potential implications for the importance of professional status of rescue workers in conferring protection from adverse mental health outcomes. PMID- 26855983 TI - An assessment of concurrent drug and alcohol use among patients seeking treatment for hepatitis C. AB - BACKGROUND: The purpose of this study was to assess the one-year prevalence of drug use and of concurrent alcohol use among hepatitis C (HCV) patients seeking treatment from specialty HCV clinics. METHODS: Patients with confirmed HCV RNA considering HCV treatment (N = 309) were recruited from university-affiliated and Veterans Affairs medical centers. RESULTS: The prevalence of current drug use in the last year was 65% (201/309) among patients considering HCV treatment. More than one-fourth of the sample used drugs at some time in their lives but none in the last year. Only 7% (22/309) of patients reported no lifetime drug use. The prevalence of concurrent drug and alcohol use in the last year was 72% (145/201) and 52% (105/201) in the last month. CONCLUSIONS: More than half of current drug users were still consuming alcohol in the last month despite the fact that they had all been informed of the potential for accelerated liver damage from continued alcohol use. This finding suggests that achieving abstinence from drug use does not necessarily imply that abstinence from alcohol has been obtained. Integration of substance treatment and HCV treatment into a unified disease management approach might increase treatment eligibility and compliance and improve disease outcomes. PMID- 26855984 TI - Valproic acid-induced hyperammonemia and minimal hepatic encephalopathy prevalence among psychiatric inpatients. AB - BACKGROUND: Our purpose was to evaluate the relationship between valproic acid (VPA)-induced hyperammonemia (HA) and the prevalence of minimal hepatic encephalopathy (MHE) cognitive impairment among psychiatric inpatients. METHODS: Fifty-two psychiatric inpatients prescribed VPA were tested for MHE impairment after achieving steady-state VPA and ammonia concentrations during hospitalization between December 2013 and June 2014. The relationship between steady-state VPA and ammonia concentration was tested by correlation coefficient. Patients completed a battery of 5 psychometric tests that determined a Psychometric Hepatic Encephalopathy Score (PHES), which was used to test the association between a PHES <-4 cutoff for MHE impairment and HA exposure (ammonia >50 MUmol/L) by chi-square testing. RESULTS: Steady-state VPA plasma concentration was not correlated significantly with ammonia concentration (r = 0.24, P = .093). The patients with HA did not have a higher proportion of MHE cognitive impairment than patients with normal ammonia exposure (43.8% vs 66.7% respectively, P = .806). CONCLUSIONS: Steady-state VPA concentration was not correlated with ammonia concentration and VPA-induced HA was not associated with a greater prevalence of MHE impairment. This suggests that the MHE impairment PHES cutoff might not detect VHE in psychiatric inpatients without cirrhosis, especially because inpatients could experience cognitive impairment related to acute mental illness. PMID- 26855985 TI - The association between pathological gambling and suicidality in treatment seeking pathological gamblers in South Africa. AB - BACKGROUND: A number of studies have noted a significant association between suicidality and pathological gambling (PG), but the exact relationship has not been extensively characterized. It is unclear whether gambling precipitates suicidality, or whether underlying psychiatric problems, such as mood disturbances, lead to both gambling and suicidality. Furthermore, all published data on the association between suicidality and gambling is from high-income countries, and the nature of this relationship in low- and middle-income countries, such as South Africa, has not been explored. METHODS: The relationship between gambling and suicidality was investigated in individuals who had called the South African National Responsible Gambling Programme's helpline. Associations between sociodemographic factors, severity of gambling symptoms, comorbid psychiatric disorders, family history of psychiatric disorders, and suicidality were assessed. RESULTS: Data indicated that suicidality in PG is associated with sociodemographic factors (female sex, being unmarried, and unemployment), clinical factors (severity of gambling, personal history of comorbid psychiatric disorders, particularly depression), and a family history of psychiatric disorders. CONCLUSIONS: A knowledge of risk factors for suicidality is important when assessing and counseling individuals who have PG, and may be a useful tool in preventing suicidal behaviors. This study provides additional evidence that treatment of PG should include a focus on comorbid psychiatric illnesses. PMID- 26855986 TI - Delirium in cardiac ICU patients. AB - BACKGROUND: The objectives of this study were to assess the incidence, course, and duration of delirium in patients admitted in the cardiac intensive care unit (ICU) and to outline risk factors associated with the occurrence of delirium. METHOD: Fifty consecutive patients admitted to a cardiac ICU were screened for the presence of delirium using Confusion Assessment Method prospectively. The risk factors associated with delirium were studied using a semi-structured form. RESULTS: Eight (16%) patients developed delirium during their stay in the cardiac ICU. The mean duration of delirium was 1.5 (SD 0.53) days. The mean days for onset of delirium were 1.63 (SD 0.74), and mean days until delirium resolved were 3.12 (SD 0.83). Fewer years of formal education and electrolyte derangement were associated with the risk of delirium (P < .05); electrolyte abnormalities accounted for 16.5% of the variance in delirium in our sample. CONCLUSIONS: One sixth of the patients admitted to the cardiac ICU had delirium; lower education and disturbed electrolytes were risk factors for delirium. PMID- 26855987 TI - Clinical characteristics and medication use patterns among hospitalized patients admitted with psychotic vs nonpsychotic major depressive disorder. AB - BACKGROUND: In routine practice, major depressive disorder (MDD) with psychotic features often goes under-recognized and undertreated. Previous research has specified several demographic and clinical differences in MDD patients with psychotic features compared with those without psychosis in routine outpatient practice, but there is little systematic research in modern routine hospital settings. METHODS: We conducted a retrospective electronic medical records chart review of 1,314 patients diagnosed with MDD who were admitted consecutively to a major psychiatric hospital over a 1-year period. We examined the prevalence of psychotic features in the sample and investigated the differences in demographic variables, clinical characteristics, and medication use patterns among patients with and without psychosis. RESULTS: The prevalence of psychotic features was 13.2% in the current hospital sample. Patients with psychotic depression were more likely to be older, male, a member of a racial/ethnic minority, and have more medical comorbidities and certain Axis I disorders compared with nonpsychotic patients. In addition, patients with psychotic depression were more likely to be prescribed antipsychotics and hypnotics before admission. CONCLUSIONS: Several demographic and clinical characteristics differentiate MDD patients with psychosis from those without psychosis in hospital settings that may be helpful in identifying these patients. Comparisons with outpatient samples and treatments implications are discussed. PMID- 26855988 TI - Deep brain stimulation for the treatment of obsessive-compulsive disorder with implications for improvements in stuttering. PMID- 26855989 TI - Does dose-response relationship further support the concept of posttraumatic OCD. PMID- 26855990 TI - Perspectives on the Positive and Negative Syndrome Scale (PANSS): Use, misuse, drawbacks, and a new alternative for schizophrenia research. AB - BACKGROUND: In 1987, Kay et al published the Positive and Negative Syndrome Scale (PANSS) and the PANSS manual to address the limitations of existing instruments for schizophrenia research. The PANSS has been one of the most widely used instruments in schizophrenia research-until now. Because of recent advances in neuroscience research, it has become essential to reevaluate the performance of the PANSS since its development 3 decades ago. METHODS: A comprehensive literature review of the PANSS from 1987 to 2015 using a PubMed search was conducted. RESULTS: Five drawbacks to the PANSS have been cited in the literature. Although several authors have pointed out flaws of the PANSS, no revisions or modifications have been attempted to address them. In addition, some researchers do not use the PANSS as intended by the authors, and other researchers misuse it. CONCLUSIONS: The PANSS is a reliable and valid instrument that has served the scientific research community well for decades. New advances in experimental psychopathology and personalized psychiatry and the new National Institute of Mental Health paradigm of Research Domain Criteria necessitate a new instrument compatible with advances in clinical neuroscience research. PMID- 26855991 TI - Dextromethorphan/quinidine withdrawal-emergent catatonia. PMID- 26855993 TI - Was fee per item really that bad? PMID- 26855992 TI - [Evaluation of Gene Expression of Hexokinases in Colorectal Cancer with the Use of Bioinformatics Methods]. AB - One of the hallmarks of cancer is the change of energy metabolism, mainly activation of glycolysis that occurs even at early stages of tumorigenesis. The glycolysis activation can be caused by overexpression of hexokinases, primarily HK1 and HK2. Colorectal cancer, which takes the third place in the cancer morbidity and mortality rates worldwide, is believed to be accompanied with overexpression of HK2, which is .considered a marker of poor prognosis. With the use of the developed CrossHub tool, we performed the analysis of the Cancer Genome Atlas RNA-Sequencing data, which, on the contrary, revealed the prevalence of the down-regulation of HK2 gene and only slight expression alterations in HK1 gene. The Cancer Genome Atlas is the largest resource in the field of molecular oncology that accumulated genomic, transcriptomic and methylomic data for thousands of sample of more than 20 cancers. The transcriptome analysis data for colorectal cancer (283 tumor samples and 41 matched normal samples) were in accord with the results of further qPCR expression level evaluation. Up regulation of HK1 and HK2 genes was observed only in a part of samples: 12% for HK1 and 30% for HK2. At the same time, the HK2 mRNA level decrease was shown in 50% of cases. Correlation analysis revealed the consistency in HK1 and HK2 expression alterations (Spearman's rank correlation coefficient r(s) = 0.43, p < 0.01), that could be explained by common deregulation mechanisms of these genes in colorectal tumors. The HK3 expression level was significantly increased in 60% of samples. Most likely, just hexokinase 3 contributes significantly to the activation of glycolysis in colorectal cancer. PMID- 26855994 TI - The Hall Technique: A Paradigm Shift in our Care of Children with Caries. PMID- 26855995 TI - Materials for Paediatric Dentistry. Part 1: Background to the Treatment of Carious Primary Teeth. AB - Dental caries is a disease that affects many people, including children, and presents numerous challenges to healthcare providers. As clinicians it is important that we consider the advantages and disadvantages of treating carious primary teeth, and make an informed decision about when it is appropriate or not. This paper describes the background to the treatment of carious primary teeth, looking at the differences between primary and permanent teeth, and the relevance of this. It also suggests points to consider when looking at restoration survival studies, as the ability to appraise the literature critically is important for us all in this 'evidence-based' age. CPD/Clinical Relevance: Our early life experiences have the ability to shape our future attitudes and behaviour. Children with carious teeth require careful management so that pain and suffering is minimized, and positive attitudes towards dentistry are fostered. PMID- 26855996 TI - Materials for Paediatric Dentistry. Part 2: The Evidence. AB - Which materials should be used to restore primary teeth? The second part in this series summarizes the current evidence base relating to this question, and describes the biological approach to caries management. CPD/Clinical Relevance: Our decisions regarding material choices should be based, where possible, on up to-date evidence. This will help to ensure that the appropriate material is placed in the appropriate clinical scenario. PMID- 26855997 TI - The Ethics of Interproximal Reduction. AB - Interproximal reduction (IPR) has become particularly popular with the use of removable aligners. Clinical and ethical factors concerning the use of interproximal reduction to facilitate orthodontic alignment are discussed. CPD/Clinical Relevance: An understanding of the aetiological factors of a malocclusion is essential to enable full discussion of the risks and benefits, or the alternatives to IPR. PMID- 26855998 TI - Globodontia in the Otodental Syndrome: A Rare Defect of Tooth Morphology Occurring with Hearing Loss in an Eight-Year-Old. AB - Otodental syndrome is a hereditary disorder comprising globodontia and sensorineural hearing loss. Globodontia is characterized by distinctively bulbous, enlarged crowns of molar and primary canine teeth. Anomalies including taurodontism and hypodontia also occur. We report on the dental treatment and multidisciplinary management of an eight-year-old girl with this rare condition. Referral to Clinical Genetics and Oral Pathology was instrumental in establishing a diagnosis of otodental syndrome for this young patient and her mother, who had similar dental defects. CPD/Clinical Relevance: To increase awareness among practitioners of this rare dental disorder and highlight the need for multidisciplinary management of such cases. PMID- 26855999 TI - An Overview of Preformed Metal Crowns. Part 1: Conventional Technique. AB - This article details the clinical techniques for conventional preformed metal crown placement. It aims to increase the readers' awareness of the clinical advantages of preformed metal crowns and the indications for their use. The second part will discuss the Hall Technique. CPD/Clinical Relevance: This two part article aims to guide the reader through the conventional and alternative techniques available for placement of a preformed metal crown whilst providing an update of the evidence for each. PMID- 26856000 TI - An Overview of Preformed Metal Crowns. Part 2: The Hall Technique. AB - Part 2 of this series of two articles addresses the Hall Technique for preformed metal crowns. It will discuss the need for an effective child and dentist friendly method to restore carious primary molars. The technique is described in detail and the evidence for its effectiveness and acceptance by children, parents, dentists and dental educators is presented. CPD/Clinical Relevance: Dentists and dental care professionals should be aware of the evidence to support the adoption of the Hall Technique. PMID- 26856001 TI - Amelogenesis Imperfecta with Coronal Resorption: Report of Three Cases. AB - Intracoronal resorption of the permanent dentition in cases of amelogenesis imperfecta (AI) is a rare finding which poses an added complication to the already complex management of this condition. This paper presents three cases of AI associated with delayed eruption of permanent teeth in which asymptomatic intracoronal resorption occurred. CPD/Clinical Relevance: This paper highlights the fact that teeth affected with amelogenesis imperfecta may undergo asymptomatic intracoronal resorption which is only identifiable radiographically. PMID- 26856002 TI - Management of Opacities in Children and Adolescents. AB - Enamel opacities can appear as white, cream, yellow or brown patches. They can result from developmental or acquired conditions. The diagnosis, severity of the opacity and patient's desire for treatment guide the clinician when choosing the correct management option. Microabrasion is indicated for surface opacities, whereas bleaching can treat opacities deep within the tooth. When these techniques have failed to achieve the desired result, camouflaging the opacity with composite resin may be useful. Novel techniques, such as infiltrating or sealing the opacity, can alter enamel's refractive index, offering further treatment choices. CPD/Clinical Relevance: There are many conservative treatments available which can improve the appearance of enamel opacities. PMID- 26856003 TI - Conservative Management of Macrodontia in the Mixed Dentition Stage--A Case Report. AB - Macrodontia is a rare dental abnormality, which can cause cosmetic concerns. Various management techniques for this condition have been documented in the literature. This case describes the initial management of macrodontia in the mixed dentition stage with the use of a minimally invasive approach to treatment. CPD/Clinical Relevance: The importance of early referral of dental abnormities is highlighted. Short- and long-term treatment options for macrodontia are described, including the impact such anomalies can have on the developing dentition. PMID- 26856004 TI - Oral Healthcare Implications of Mass Migration. AB - Population movements, whether voluntary or forced, are an integral part of an increasingly globalized society and, while the health needs of migrant populations cannot be generalized, some migrants can have worse oral health outcomes compared with their host-country counterparts, with their first dental contact typically being for emergency care. Failure to provide immediately necessary treatment may be unlawful under the Human Rights Act 1998. CPD/Clinical Relevance: NHS dental services need to evolve and address the challenges inherent in caring for vulnerable migrants. Education and appropriate training needs to be developed for the dental profession in order to enable new ways of promoting intersectoral care and community engagement. PMID- 26856005 TI - Idiopathic Radiographic Apical Root Resorption in Wind Instrument Players. AB - Root resorption of the permanent teeth involves an elaborate interaction among inflammatory cells resulting in loss of dental hard tissues. This report describes three clinical cases where idiopathic root resorption occurred in wind instrument playing patients. These patients produce adequate non-orthodontic forces, while playing their instruments, to expose their teeth to root resorbing force. Careful clinical monitoring of patients' teeth should be undertaken, as the additive effects of orthodontic treatment and musical habits are unknown. CPD/Clinical Relevance: This paper advises that questioning about wind instrument playing during case history-taking would be beneficial to clinicians. Furthermore, careful clinical monitoring of these patients' teeth during orthodontic treatment should be undertaken. PMID- 26856006 TI - Case Report: An Unusual Finding of a Solitary Bone Cyst in a Patient with a Fractured Mandible. AB - Solitary bone cysts are uncommon. They have a reported incidence of 0.6% and are commonest in the mandible. The case of a 16-year-old patient who attended Accident and Emergency with a fractured mandible and the incidental finding of a solitary bone cyst is presented. Solitary bone cysts are usually asymptomatic and generally heal fully following surgical exploration. CPD/Clinical Relevance: This case report aims to increase awareness of the general dental practitioner of solitary bone cysts as a possible finding in patients with pathological jaw fractures and radiolucencies of the jaws. It outlines the surgical management that is carried out on patients with solitary bone cysts. PMID- 26856007 TI - Dear Editor. PMID- 26856008 TI - Depression, selective serotonin reuptake inhibitors and bruxism. PMID- 26856009 TI - Anti-thrombotic agent reversal is possible. PMID- 26856010 TI - Dear Editor. PMID- 26856011 TI - Clinical Challenges Q&A. 16. Swelling in the Anterior Gingivae. Diagnosis: Gingival cyst. PMID- 26856012 TI - Technique Tips--Access Cavity Walkthrough: Lower Mandibular First Molar. PMID- 26856013 TI - Blinded Clinical Evaluation of a New Toothbrush Design. AB - OBJECTIVE: The purpose of this single-blind, crossover study was to compare plaque removal associated with a new manual toothbrush, the O'Nano and a best selling, commercially available manual toothbrush, the Oral-B Indicator 40. The O'Nano toothbrush has a patented "one-piece molded design" made of Thermal Plastic Urethane, a plastic that has been used in medical devices. METHODOLOGY: Over a six-week period, 40 subjects participated. Following random assignment, 22 subjects started with the O'Nano brush and the remaining started with the Oral-B Indicator 40 brush. Crossover occurred after two-weeks' use of each brush (two week washout in between). Plaque was scored before and after brushing using the Turesky modification of the Quigley-Hein Index (T/Q-H). Plaque accumulation was 12 to 18 hours prior to examination and brushing. RESULTS: Thirty-nine subjects completed the study; one subject was dropped for non-compliance. Groups were virtually identical at the onset in plaque level scores by study design. In comparison to baseline, both brushes achieved significant (p < 0.001) plaque reductions (gains) with a matched-paired comparison t-test. The O'Nano brush gain was 0.445 (18%) per subject and the Oral-B Indicator 40 brush was 0.504 (20%) per subject. The difference in plaque removal capability between brushes averaged 0.60 in favor of the Oral-B Indicator 40 brush, a non-significant (p = 0.20) finding determined by a matched-paired comparison t-test, which is identical to the repeated measures ANOVA when there are two groups and two time periods. Standard deviation (SD) was smaller for the O'Nano brush in plaque reduction scores (0.183 < 0.235). This difference was tested and found to be non significant with this particular group size. CONCLUSION: Statistical analysis of T/Q-H scores demonstrated that the O'Nano brush is comparable to the Oral-B Indicator 40 brush under the conditions of this study protocol. With this small study group the slight differences in plaque removal efficiency between both brushes was not significant. The unique "one-piece molded" design of the O'Nano brush was not evaluated for durability in comparison to a more conventional brush, the Oral-B 40. PMID- 26856014 TI - Long-Lasting Efficacy of an Experimental 1450 ppm Fluoride/Zinc-Based Dentifrice as Measured by Calcium Buildup Using an In Situ Intra-Oral Device After 12 Hours: A Randomized Clinical Trial. AB - OBJECTIVE: To assess the efficacy of an experimental 1450 ppm fluoride as sodium monofluorophosphate (SMFP)/zinc-based dentifrice (Test), a clinically proven 1450 ppm fluoride as SMFP/zinc-based dentifrice (Positive Control), and a 1000 ppm fluoride as SMFP and 450 ppm fluoride as sodium fluoride (NaF) dentifrice (Negative Control) in delivering 12-hour anti-tartar benefits as measured by calcium buildup after a single product brushing. METHODS: Fourteen (14) adult subjects completed this single-center, double-blind, randomized, cross-over clinical study conducted in Piscataway, New Jersey. An intra-oral appliance was custom-made for each subject as a surface on which the anti-calculus agents' inhibition of early calculus formation could be analyzed. After brushing with their assigned toothpaste, each subject wore their respective appliance for 12 hours overnight. When the appliance was removed, it was washed, suspended in 0.1 MHCL to release Ca2+ from deposits, and analyzed by Inductively Coupled Plasma (ICP) for deposited calcium. There was a one-week washout period between each product use. Statistical analyses were performed on the mean level of calcium (MUg). Comparisons of the treatment groups with respect to 12-hour post-brushing (overnight) calcium levels were performed via a two-way analysis of variance (ANOVA), with subjects and products as factors in the ANOVA model. Post-ANOVA pair-wise comparisons of the study treatments were performed using the Tukey's test for multiple comparisons. All statistical tests of hypothesis were two sided, and employed a level of significance of alpha = 0.05. RESULTS: At the 12 hour post-brushing examination, the mean level of calcium buildup was 0.46 MUg for subjects assigned to the experimental Test dentifrice, 0.41 MUg for subjects assigned to the Positive Control dentifrice, and 2.47 MUg for subjects assigned to the Negative Control dentifrice. After 12 hours post-brushing, subjects assigned to the experimental Test dentifrice and Positive Control dentifrice both exhibited statistically significantly (p = 0.005 and p = 0.004, respectively) lower levels of calcium buildup as compared to the subjects assigned to the Negative Control dentifrice. No statistically significant (p = 0.996) difference was observed between the experimental Test dentifrice and Positive Control dentifrice with respect to tartar control efficacy after 12 hours post-brushing. No adverse effects of the hard or soft oral tissue were observed by the clinical investigators or reported by the subjects. CONCLUSION: Both the experimental Test dentifrice (1450 ppm fluoride as SMFP/zinc-based dentifrice) and the Positive Control dentifrice (1450 ppm fluoride as SMFP/zinc-based dentifrice) provided significantly greater 12-hour tartar control as measured by calcium buildup, as compared to the Negative Control dentifrice containing 1000 ppm fluoride as SMFP and 450 ppm fluoride as NaF. PMID- 26856015 TI - A Randomized Clinical Study Investigating the Stain-Removal Potential of Two Experimental Dentifrices. AB - OBJECTIVE: To evaluate the ability of two experimental desensitizing dentifrices, both containing a chemical cleaning agent, one with ultra-low abrasivity and one with low abrasivity, a standard fluoride dentifrice, and a daily-use whitening dentifrice to remove extrinsic tooth stain. METHODS: This was a single-center, examiner-blind, randomized, controlled, four-treatment, parallel-group study in healthy adults. Extrinsic stain was evaluated using the Macpherson modification of the Lobene Stain Index (MLSI). At baseline, eligible subjects with a total MLSI (area x intensity [A x I]) score of 15 for the facial surfaces of the 12 anterior teeth were stratified (based on total MLSI [A x I] score [< 45 = low; >= 45 = high] and smoking status) and randomized to treatment with one of four dentifrices: an experimental ultra-low abrasivity desensitizing dentifrice (relative dentin abrasion [RDA] -12); an experimental low abrasivity desensitizing dentifrice (RDA -40); a standard fluoride dentifrice with moderate abrasivity (RDA -80); and a whitening dentifrice with higher abrasivity (RDA 142). Both desensitizing dentifrices contained 5% potassium nitrate and 5% sodium tripolyphosphate (a chemical cleaning agent). Treatment effects were evaluated after four and eight weeks of twice-daily brushing. RESULTS: In total, 142 subjects were randomized and 133 subjects completed the study. All study dentifrices demonstrated statistically significant reductions in extrinsic tooth stain from baseline after four and eight weeks of twice-daily use (p < 0.01). There were no statistically significant between-treatment differences for the primary variable (mean MLSI [A x I] score across all assessed sites) at four or eight weeks, and no notable trends were observed. CONCLUSION: All study dentifrices reduced extrinsic tooth stain. The experimental ultra-low and low abrasivity desensitizing dentifrices containing 5% sodium tripolyphosphate performed similarly to both a moderate abrasivity standard fluoride dentifrice and a higher abrasivity whitening dentifrice. PMID- 26856016 TI - Control of Established Gingivitis and Dental Plaque Using a 1450 ppm Fluoride/Zinc-based Dentifrice: A Randomized Clinical Study. AB - PURPOSE: To investigate the clinical efficacy in controlling established gingivitis and dental plaque of a 1450 ppm fluoride as sodium monofluorophosphate (SMFP)/zinc-based dentifrice, as compared to a zinc-free dentifrice with 1450 ppm fluoride as SMFP after six months product use. METHODS: A six-month clinical study, with eighty-six (86) subjects, was conducted in Chengdu, China, using a double-blind, randomized, parallel-group treatment design. After a baseline evaluation, study subjects were randomly assigned to one of the two study treatments: 1) 1450 ppm fluoride as SMFP/zinc-based dentifrice (Test) or 2) 1450 ppm fluoride as SMFP/zinc-free dentifrice (Negative Control). Subjects were provided with a soft bristle toothbrush and brushed their teeth twice daily (morning and evening) for one minute with their assigned dentifrice. After three months, and again after six months of product use, subjects returned to the testing facility for their followup gingivitis and plaque examinations. Statistical analyses were performed separately for the gingivitis assessments and dental plaque assessments using the appropriate statistical methods. All statistical tests of hypotheses were two-sided, and employed a level of significance of alpha = 0.05. RESULTS: After three and six months of product use, subjects assigned to the Test treatment exhibited statistically significant (p < 0.001) reductions in gingival index and plaque index scores as compared to subjects assigned to the Negative Control treatment. CONCLUSION: The results of this single-center, double-blind, parallel-group and randomized clinical study support the conclusion that a 1450 ppm fluoride as SMFP/zinc-based dentifrice provides clinically meaningful and statistically significant reductions in gingivitis (23.8%) and dental plaque (22.5%) as compared to a 1450 ppm fluoride as SMFP/zinc-free dentifrice over a six-month period of twice-daily product use. PMID- 26856017 TI - Case Series Report of 66 Refractory Maintenance Patients Evaluating the Effectiveness of Topical Oxidizing Agents. AB - OBJECTIVE: To evaluate the clinical effects of a prescription tray application of hydrogen peroxide gel as an adjunct to frequent maintenance appointments for refractory periodontal patients. METHODS: Case series data were analyzed from 66 failing periodontal maintenance patients who had exhausted treatment options before using prescription trays with a 1.7% hydrogen peroxide gel once or twice daily for two-and-a-half to five years. Data included pocket probing depths (PPD), bleeding on probing (BOP), smoking status, and compliance with tray usage. Data were collected prior to tray usage and after tray delivery at six months, one year, and annual intervals. RESULTS: A clinical and statistical reduction in BOP was maintained over the length of the study (p <= 0.01). No differences were seen in patients who used trays two times or one time a day or in patients who smoked or did not smoke. The 1.7% peroxide delivered via a prescription tray was most effective in shallow pockets. Aggregate PPD distribution did not change significantly. Of clinical relevance, only one tooth out of 1,745 teeth studied was lost due to periodontal disease during the study period. CONCLUSION: Prescription tray application of peroxide gel, as an adjunct to frequent periodontal maintenance appointments for refractory patients, demonstrated significant reductions in BOP'for smokers and non-smokers who used tray delivery once or twice a day. PMID- 26856018 TI - Market Feedback on the Long-Term Impact of the Affordable Care Act. PMID- 26856019 TI - The Integration of Two Healthcare Systems: A Common Healthcare Problem. AB - The change in reimbursement mandated by the Affordable Care Act is causing a rapid consolidation of the marketplace as well as the delivery of clinical care in a team-based model. This case report examines the successful joining of two clinical teams concurrent with the merger of two healthcare organizations and discusses some of the difficulties encountered. A subsequent discussion focuses on the resolution: the need for physicians to embrace the team concept of healthcare delivery and for healthcare systems to facilitate this transition with team and leadership coaching. PMID- 26856021 TI - Integration of Medical Scribes. AB - This article discusses reasons to employ medical scribes and why scribes play a critical role in both hospitals and private practices. Scribes are able help physicians with documentation and increase productivity. Physicians are able to fully engage with patients while the scribe documents the encounter in real-time. Although scribes are unlicensed, they still need to be recruited and trained in the same manner as any other medical professional. PMID- 26856020 TI - Physician Posture at the Bedside: A Study of African-American and Hispanic Patient Preferences at a Teaching Hospital. AB - The physician-patient interaction is central to any clinical encounter. Although the technical components of the interaction are conveyed by verbal communication, the nonverbal cues are instrumental in setting up the physician-patient relationship and carrying it forward. Often, patient preferences in terms of non verbal communication cues depend on the ethnicity of the patient. In this article, we present a study of Hispanic and African-American patients regarding their preference of physician posture. Together, these groups represent almost one third of the U.S. population. In our study, a majority of patients preferred their physicians to be seated during the medical interview. Although these results were similar across cultural groups, subtle differences were observed in patient preference regarding other nonverbal communication methods by physicians. It is important for physicians to be aware of these differences. Including course work that highlights cultural sensitivities in the medical school curriculum is a good way to create awareness among the next generation of physicians. PMID- 26856022 TI - The Future of Retail Medicine: A Paradigm Shift in Consumer Preferences and Demands. PMID- 26856023 TI - How to Create "Wow" for Your Patients. AB - It is going to become very important to pay attention to patient satisfaction, because soon physicians' incomes will be based on how well they provide their patients with a positive experience. It will not be adequate to just make the diagnosis and treat the patient successfully. All physicians are trained to do that. Now patient satisfaction will require that physicians go above and beyond merely providing a diagnosis and treatment. This article suggests 11 techniques to provide patients with a "wow" experience and achieve outstanding patient satisfaction. PMID- 26856024 TI - Managing Pessimistic, Gloomy, and Cynical Employees: Twenty-Five Do's and Don'ts. AB - Every medical practice manager has to deal with a certain amount of employee pessimism at times. But one overly pessimistic employee can spread his or her negativity to the entire medical practice team if the manager doesn't intervene. This article suggests practical strategies managers can use to deal effectively with a pessimistic, defeatist, gloomy, or cynical employee. It describes two kinds of pessimism medical practice managers may encounter and offers 25 specific management do's and don'ts for managing a pessimist. This article also offers managers guidance for firing a pessimistic employee, including sample language they can use. It provides 10 self-care strategies for practice managers so they can keep themselves from succumbing to an employee's negativity. It also suggests eight ways that pessimism can hurt the medical practice team and describes five kinds of negative thinking managers may encounter. Finally, this article explores defensive pessimism theory and the surprising benefits for managers of some pessimistic thinking. PMID- 26856025 TI - Payroll: A Headache You Can Cure! AB - Payroll is not only an expense for your practice; it can be a headache for you or your practice manager. Payroll is also a major scope of audit procedures. Don't rely on the word of anyone else that your taxes were processed and remitted. Demand to see proof. By outsourcing your human resources and payroll functions to one company, you can free up valuable time to concentrate on your area of expertise, leaving the administrative hassles to the staffing firm. PMID- 26856026 TI - United States Supreme Court Decisions; Affordable Care Act Modification; IRS Determination Letter Program. PMID- 26856027 TI - Focus On Impact for a Profit-Driven Medical Practice. Part II: Six Processes You Can Use to Maximize and Capitalize on the Uniqueness of Your Practice. AB - This article presents the second part of the proven Focus on Impact strategic model for practice growth. It spotlights six specific processes you can use to maximize and capitalize on the uniqueness of your practice to increase revenues, enhance patient care and service, improve executive team alignment and intra- and interdepartmental teamwork, and dramatically reduce conflict and stress among practice personnel. PMID- 26856028 TI - Responding to Audits: Managed Care, Medicare, and Medicaid ... Oh My! PMID- 26856029 TI - The Relationship Among Heart Failure Disease Management, Quality of Care, and Hospitalizations. AB - Heart failure (HF) affects 5.1 million adult patients, accounting for over 1 million hospitalizations, 1.8 million office visits, and nearly 680,000 emergency department visits annually. HF hospitalizations have been incorporated into a national measure of hospital and provider quality, with associated financial penalties based on the 30-day readmission rate after an index hospitalization for HF. However, it is not clear whether the number of HF-related hospitalizations or 30-day readmissions is consistently related to quality of care. The relationships between various measures of HF care quality and hospitalization rates were evaluated by performing a cohort study of an HF disease management program in a clinical practice setting. Following the statistical analyses assessing outcomes and survival, the conclusion was that an HF disease management program in clinical practice associated with improved utilization of evidence-based medical and device therapies tends to improve ejection fraction and survival, and reduce sex and race disparities, but not with an associated reduction in hospitalizations or total hospital days. PMID- 26856030 TI - Ten Reasons to be Glad You Are a Physician. AB - There is no shortage of topics for physicians to complain about: a decrease in reimbursements, rising overhead costs, and decreasing physician incomes, to list just a few. The variables also may include patient dissatisfaction, the risk of litigation, deterioration in staff morale, and poor financial decisions, including poor performance in the doctor's stock market portfolio. However, the number of applicants for medical schools has not decreased, even though physicians graduate with an average of $250,000 of debt. We suggest that physicians take a good look at what our profession offers and reflect on why healthcare (i.e., medical practice) is such a desirable occupation, and show that we should be more grateful and thankful rather than griping and resentful. PMID- 26856031 TI - Turning Experts into Bumblers: The Peter Principle Revisited. PMID- 26856033 TI - The Only Safe SMS Texting Is No SMS Texting. AB - Many physicians and practice staff use short messaging service (SMS) text messaging to communicate with patients. But SMS text messaging is unencrypted, insecure, and does not meet HIPAA requirements. In addition, the short and abbreviated nature of text messages creates opportunities for misinterpretation, and can negatively impact patient safety and care. Until recently, asking patients to sign a statement that they understand and accept these risks--as well as having policies, device encryption, and cyber insurance in place--would have been enough to mitigate the risk of using SMS text in a medical practice. But new trends and policies have made SMS text messaging unsafe under any circumstance. This article explains these trends and policies, as well as why only secure texting or secure messaging should be used for physician-patient communication. PMID- 26856032 TI - Taking a Pulse on Your Practice. AB - Each medical practice, like a living organism, occasionally requires reading of its vital signs. As with human beings, one of those vital signs is the pulse. For your medical practice, just like your patients, there are numerous places from which to take that reading. This article reviews seven key pulses that provide insight into what is happening within the workplace culture of your practice. PMID- 26856034 TI - Top Ten Embezzlement Risks in Your Medical Practice. AB - Medical practices are often faced with employee embezzlement and theft. To protect themselves and their practices, physicians and practice executives should have in place policies and procedures for identifying and handling unethical behaviors by employees. This article deals with the common risks in healthcare practices and provides suggestions to help mitigate the risk of embezzlement. PMID- 26856035 TI - SCHISTOSOMA MANSONI INFECTION AND THE ASSOCIATED ANTIBODY IMMUNE RESPONSE AMONGST RESIDENTS OF KIGUNGU ENTEBBE, UGANDA. AB - BACNKGROUND: There are many foci endemic for Schistosoma (S.) mansoni in Uganda. The immune responses to infection with the parasites in these areas have been found to vary with host sex, age and infection intensity. OBJECTIVE: To determine the profile of antibody isotypes responses against S. mansoni crude soluble egg antigens (SEA) and soluble adult worm protein (SWAP) antigens that determine the host resistance or susceptibility to reinfection. DESIGN: Cross Sectional, cohort study. SETTING: Kigugu fishing village in Entebbe, Uganda. SUBJECTS: Nine hundred and forty five (945) Kigungu residents reported forpre-treatment screening and enrolment and 626 cohorts report for post-treatment screening and enrolment 18 months later. RESULTS: Pearson's Chi-sq2 showed thatincrease in titres of anti (SWAP IgE, SEA IgE, and SEA IgG2) was not significant, but increase in anti SEA IgG3 was significant. Decrease in titres of anti (SWAP IgG1, SEA IgG1, and SEA IgG4) was not significant but decrease of anti (SWAP IgG2, SWAP IgG3 and SWAP IgG4) was significant. Positive correlation existed between age and anti SWAP IgE in before and after treatment sera. On the contrary, age was positively correlated with anti SWAP IgG4 in pre-treatment sera but was negatively correlated with anti SWAP IgG4 in the post-treatment sera. In addition there were positive correlation between higher egg counts and the immunoglobulin levels of anti SWAP IgG4 and anti SEA IgG4 but negative correlations were observed between anti SWAP IgE and anti SEA IgE. Conversely low egg counts were associated with high levels of anti SWAP IgE. Furthermore, IgG1-4, IgE antibody to SEA and SWAP antigens did not differ significantly according to sex. CONCLUSION: We concluded that praziquantel treatment of S. mansoni infected persons alter the immune responses that are influenced by age and intensity. A phenomenon that is useful in the effort to produce vaccine against schistosome. PMID- 26856037 TI - REMINDER SYSTEMS FOR SELF UTERINE MASSAGE IN THE PREVENTION OF POSTPARTUM BLOOD LOSS. AB - BACKGROUND: Uterine massage may significantly reduce post partum blood loss and could be patient-driven. OBJECTIVE: To assess the effectiveness of an alarm reminder system for self uterine massage in the prevention of post partum blood loss. DESIGN: A random controlled trial. SETTING: Meru District Hospital, Kenya. SUBJECTS: One hundred and twenty seven (127) women were randomly assigned to a 15 minute alarm reminder system (71) and non-alarm (56) control arm during the fourth stage of labour. RESULTS: Uterine massage compliance was better in the alarm group compared to the non-alarm group (Average massage of seven and two in two hours respectively P-value <0.0001), however the difference in blood loss was not significant 45.6 ml (95% CI 43-46) vs 47.1 ml (95% CI 43-52)ml p-value 0.892. CONCLUSION: Uterine massage compliance is remarkably increased by the use of an alarm reminder. PMID- 26856036 TI - MANAGEMENT AND OUTCOME OF PATIENTS WITH WILMS' TUMOUR (NEPHROBLASTOMA) AT THE MOI TEACHING AND REFERRAL HOSPITAL, ELDORET, KENYA. AB - BACKGROUND: Wilms' tumour is a common malignant neoplasm of the kidney and is ranked among the top six solid tumours in children in Kenya. Despite its rapid growth and therefore debilitating effects on its victims, it is one tumour that has shown good response to combined modality approach to its treatmentwith encouraging possibilities of survival even in resource poor settings. OBJECTIVE: To evaluate the management and outcome of patients with Wilms'tumour attended to at Moi Teaching and Referral Hospital (MTRH) during the period between January 2000 and December 2007. DESIGN: Retrospective Study. SETTING: The Paediatric Oncology Service (Oncology unit in the Paediatric Ward, the Paediatric Surgical Ward and the Outpatient Oncology Clinic) at the Moi Teaching and Referral Hospital, Eldoret, Kenya. RESULTS: Information of 45 patients diagnosed with Wilms' tumour was analysed. Forty two (93%) of the patients were referrals from various health facilities in the region. Twenty three (51%) were male and 34 (76%) were aged less than 48 months. Twenty five (56%) had the left kidney affected, 19 (42%) the right kidney and one (2%) bilateral. All the 45 (100%) had an abdominal ultrasound done but none had exhaustive investigations done to stage the disease. Only eight (18%) of the patients had a medical insurance cover. Fourty one (91%) of the patients received specific cancer treatment with 28 (62%) getting combined modality treatment. Nineteen (42%) were lost to follow up. Thirty (67%), 21 (47%), 15 (33%) and 13 (29%) patients were alive six months, one year, two years and three years respectively from the time of diagnosis. 29% survived beyond three years of diagnosis. CONCLUSION: Staging of Wilms tumour fell short of the expected. Neo-adjuvant chemotherapy reduced morbidity and mortality of patients managed for Wilms' tumour. Loss to follow up and cost of treatment had a negative impact on the outcome, a situation that requires to be improved. PMID- 26856038 TI - FACTORS INFLUENCING VITAMIN A SUPPLEMENTATION AMONG MOTHERS OF CHILDREN UNDER FIVE YEARS OLD AT MBAGATHI DISTRICT HOSPITAL, KENYA. AB - BACKGROUND: Vitamin A supplementation is one of the best-proven and most costeffective interventions to improve vitamin A status and save children's lives. OBJECTIVE: To assess factors affecting practices and utilisation of Vitamin A supplementation services among mothers with children below five years attending Mbagathi District Hospital. DESIGN: Cross-sectional descriptive study. SETTING: Mbagathi District Hospital (MDH) Maternal and Child Health Clinic (MCH) and Paediatric Out Patient Department (POPD). SUBJECTS: Mothers attending MDH MCH and POPD. MAIN OUTCOME MEASURES: Utilisation, Practices and Awareness of vitamin A supplementation (VAS). RESULTS: A total of one hundred and fifty eight respondents were interviewed. About a half (52%) of the respondents had their children up to date with VAS while less than a half (43%) of the mothers had received vitamin A after delivery. Three quarters of the respondents'children had missed the vitamin A capsule because they were either not aware of schedule (41%) or had stopped coming to clinic (35%). This notwithstanding, 91% of the respondents neither encountered any problems when seeking VAS services nor had negative beliefs or superstitions about vitamin A. CONCLUSION: The main factors affecting utilisation of VAS services was lack of information and awareness among both health workers and mothers. These services are averagely well utilised at MDH though still below the National 80% coverage target. PMID- 26856039 TI - AN UNUSUAL PRESENTATION OF ACUTE LYMPHOBLASTIC LEUKAEMIA WITH PERI-CARDIAL EFFUSION CAUSING CARDIAC TAMPONADE. AB - Peri-cardial effusion is most commonly associated with tuberculous infection in the developing world. Peri-cardial effusion causes symptoms when it is large or when it has accumulated rapidly. Non-tuberculous causes of peri-cardial effusion include bacterial infections, uraemia, viral infections, rheumatic fever, connective tissue disorders, post - peri-cardiotomy syndromes and malignancy. We present a case of acute lymphoblastic leukaemia first presenting as a large peri cardial effusion causing tamponade. PMID- 26856040 TI - PREDICTORS OF INCIDENT TUBERCULOSIS IN HIV-EXPOSED CHILDREN IN TANZANIA. AB - OBJECTIVE: To examine the predictors of tuberculosis infection in HIV-exposed children. DESIGN: A longitudinal cohort study nested within a randomised controlled trial. SETTING: Antenatal clinics in Dar-es-Salaam, Tanzania. SUBJECTS: Children born to 875 HIV-infected women in Tanzania. RESULTS: A total of 82 children developed tuberculosis during the follow-up period. In multivariate analyses, HIV infection was associated with a six-fold increase in risk of tuberculosis. Breastfeeding duration, child mid-upper arm circumference, and maternal CD4 T-cell counts were inversely related to risk of tuberculosis. In HIV-infected children, greater number of people eating at the same household meal and child CD8 T-cell counts were associated with increased risk of tuberculosis; higher maternal lymphocyte counts, increased duration of breastfeeding, and lower vitamin E levels were associated with reduced risk of tuberculosis. In HIV uninfected children, breastfeeding duration and increased child mid-upper arm circumference were associated with reduced risk of tuberculosis. CONCLUSION: Breastfeeding duration, HIV status, maternal and child nutritional and immunological status were important predictors of child tuberculosis. Appropriate infant feeding and nutritional interventions could represent important adjuncts to prevent tuberculosis in children born to HIV-infected women in sub-Saharan Africa. PMID- 26856041 TI - FEMALE GENITAL MUTILATION: ARE WE WINNING? AB - BACKGROUND: For more than 25 years, efforts have been geared towards curtailing the practice of female genital mutilation (FGM) in countries like Nigeria. This study was designed to see if all these efforts have made any impact in reducing the prevalence of FGM appreciably in the south-West of Nigeria. OBJECTIVE: To determine the prevalence of female genital mutilation and profiling the trends of FGM affected patients. DESIGN: A prospective study based on direct observation of the external genitalia by health-care workers . SUBJECTS: Five hundred and sixty five females less than 15 years of age. SETTING: The children emergency and gynaecological wards of the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria from 1st of January to December 31s 2007. RESULTS: Forty one point nine percent of the patients examined had female genital mutilation, 93.2% of these had the procedure before attaining the age of one year. Type 2 FGM predominated (58.22%). The procedure was performed predominantly (64.6%) by traditional birth attendants. The decision to have the procedure done was influenced in 78% of cases by mothers and grandmothers. In 35.4% of cases, there were immediate and short term complications. Demands of tradition predominated (59.1%) as the most important reason for the practice of female genital mutilation. CONCLUSION: The practice of FGM appears to be still highly prevalent and resistant to change probably due to deep rooted socio-cultural factors. Strategies such as public education campaigns highlighting its negative impact on health and disregard for human rights should be evolved. PMID- 26856042 TI - SEROPREVALENCE OF HAV, HBV, HCV, AND HEV AMONG ACUTE HEPATITIS PATIENTS AT KENYATTA NATIONAL HOSPITAL IN NAIROBI, KENYA. AB - BACKGROUND: Acute viral hepatitis is most frequently caused by the hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV) and hepatitis E virus (HEV). OBJECTIVES: To determine seroprevalence of HAV, HBV, HCV and HEV among patients with acute hepatitis in Nairobi, Kenya, elucidate various risk factors for hepatitis viral infection and determine the co infection rates with these viruses in the acute hepatitis patients. DESIGN: Across sectional descriptive study. SETTING: Kenyatta National Hospital, from November 2007 to April 2008. SUBJECTS: One hundred patients were recruited by purposive sampling method and comprised of 57 males and 43 females. RESULTS: Among the enrolled patients, twenty three tested positive for one or more markers of acute viral hepatitis, that is, HAV, HBV, HCV and HEV. No markers were detected in 77patients, 2% tested positive for IgM anti-HAV 11% for IgM anti-HBc; 3% for HBsAg; 5% for HCV RNA and 7% for IgM anti-HEV.Various risk factors associated with acute viral hepatitis were identified; poor sanitation, source of water, occupation, place of residence, level of education, household size, drug abuse and sexual behaviours. Co-infection rate with hepatitis Viruses was at 4%, IgM anti-HAV and IgM anti-HEV 1% (n=1); IgM anti-HBc and IgM anti-HEV 1% (n=1); IgM anti-HBc and anti-HCV 2% (n=2). Three patients were positive for HBsAg; among this two were negative for IgM anti-HBc and this accounted for HBV carriage (2%). CONCLUSION: Hepatitis viruses'infections are commoncause of hepatitis among patients with acute hepatitis at Kenyatta National Hospital. Co-infection with these viruses was also identified among these patients. PMID- 26856043 TI - PREVALENCE OF ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODIES IN PATIENTS CLASSIFIED AS RHEUMATOID AND UNDIFFERENTIATED ARTHRITIS AT KENYATTA NATIONAL HOSPITAL. AB - BACKGROUND: Rheumatoid arthritis(RA) is a debilitating condition.Early diagnosis of RA can be difficult as the disease may initially be indistinguishable from Undifferentiated arthritis(UA). American College of Rheumatology criteria(ACR)is not suitable for early diagnosis as its characteristics are fulfilled when bone damage has already taken place.Anti-cyclic citrullinated antibodies(Anti-CCP) are highly specific for RA and have been used to confirm early diagnosis. OBJECTIVE: To determine the prevalence and clinical utility of Anti-CCP antibodies in patients with rheumatoid and undifferentiated arthritis at presentation to KNH medical clinics. Design: A cross-sectional descriptive study. SETTING: Kenyatta National Hospital Medical Outpatient Clinics (MOPCs) between the month of October 2008 to February 2009. RESULTS: A total of 95 patients were recruited.The mean age of the patients studied in the RA and UA was 44.7 and 41.2(p=0.356) respectively. Sixty four patients(64) satisfied ACR criteria.The overall prevalence of Anti-ccp antibodies in the population studied was 47.4%.The prevalence of Anti-ccp antibodies in patients who satisfied the ACR criteria was 62.5%.The prevalence of Rheumatoid Factor (RF) in patients who satisfied the ACR criteria was 50% compared to 9.7% for those who did not(p=0.000). The male to female ratio of subjects studied was 1:11. CONCLUSION: Anti-ccp antibodies are more prevalent in this cohort of patients with rheumatoid and undifferentiated arthritis than RF It was also concluded that ACR characteristics correlated well with Anti-ccp and RF. A greater percentage of patients who were RF negative were Anti-ccp positive. PMID- 26856044 TI - ANTIMICROBIAL PROPERTIES OF HUGONIA CASTENEIFOLIA AND ITS POTENTIAL USE FOR THE CONTROL OF OPPORTUNISTIC INFECTIONS. PMID- 26856045 TI - AN APPARENTLY AGGRESSIVE CRANIOFACIAL OSTEO-DYSPLASTIC LESION PRECIPITATING DEBILITATING SYMPTOMS AND SIGNS: CASE REPORT. AB - This is a case report of an 18 year old man with craniofacial fibro-osteo dysplastic lesion which exhibited both exophytic and endophytic growth patterns. We discuss the extent of tumour growth and its associated secondary changes. PMID- 26856046 TI - Introduction: Early Modern Color Worlds. PMID- 26856047 TI - Writing on Pigments in Natural History and Art Technology in Sixteenth-Century Germany and Switzerland. AB - Renaissance painters used a number of inorganic color materials. The development of mineralogy as a discipline opened a new discourse on mineral pigments. Agricola and other naturalists were familiar with the contemporary writings on art technology, but their focus was different. Therefore, the exchange of knowledge between these two color worlds remained selective. One possible meeting point was the Kunstkammer where the study of natural objects and materials was combined with an interest in the manual execution of a painting. PMID- 26856048 TI - Ulisse Aldrovandi's Color Sensibility: Natural History, Language and the Lay Color Practices of Renaissance Virtuosi. AB - Famed for his collection of drawings of naturalia and his thoughts on the relationship between painting and natural knowledge, it now appears that the Bolognese naturalist Ulisse Aldrovandi (1522-1605) also pondered specifically color and pigments, compiling not only lists and diagrams of color terms but also a full-length unpublished manuscript entitled De coloribus or Trattato dei colori. Introducing these writings for the first time, this article portrays a scholar not so much interested in the materiality of pigment production, as in the cultural history of hues. It argues that these writings constituted an effort to build a language of color, in the sense both of a standard nomenclature of hues and of a lexicon, a dictionary of their denotations and connotations as documented in the literature of ancients and moderns. This language would serve the naturalist in his artistic patronage and his natural historical studies, where color was considered one of the most reliable signs for the correct identification of specimens, and a guarantee of accuracy in their illustration. Far from being an exception, Aldrovandi's 'color sensibility'spoke of that of his university-educated nature-loving peers. PMID- 26856049 TI - Red, White and Black: Colors of Beauty, Tints of Health and Cosmetic Materials in Early Modern English Art Writing. AB - Alongside Richard Haydocke's translation of Giovanni Paolo Lomazzo's treatise on painting (1598), the article examines concepts of color concerning cosmetics, painting and complexion as they relate to aesthetics, artistic and medical practice in the sixteenth and seventeenth centuries. Beginning with white and red as ideal colors of beauty in Agnolo Firenzuola's Discourse on the beauty of women (1541), the essay places color in relation to major issues in art, medicine and empiricism by discussing beauty as a quality of humoral theory and its colors as visual results of physiological processes. Challenging the relation of art and nature, gender and production, Lomazzo's account of complexion and Haydocke's additions on cosmetic practices and face-painting provide key passages that shed light on the relation of cosmetics colors, art writing and artistic practices at the convergence of the body, art and medicine in the context of the emerging English virtuosi around 1600. PMID- 26856050 TI - Color and Contingency in Robert Boyle's Works. AB - This essay investigates the relationship between color and contingency in Robert Boyle's Experiments and Considerations Touching Colours (1664) and his essays on the unsuccessfulness of experiments in Certain Physiological Essays (1661). In these two works Boyle wrestles with a difficult practical and philosophical problem with experiments, which he calls the problem of contingency. In Touching Colours, the problem of contingency is magnified by the much-debated issue of whether color had any deep epistemic importance. His limited theoretical principle guiding him in Touching Colours, that color is but modified light, further exacerbated the problem. Rather than theory, Boyle often relied on craftsmen, whose mastery of color phenomena was, Boyle mentions, brought about by economic forces, to determine when colors were indicators of important 'inward' properties of substances, and thus to secure a solid foundation for his experimental history of color. PMID- 26856051 TI - The Saline Chymistry of Color in Seventeenth Century English Natural History. AB - Before Newton's seminal work on the spectrum, seventeenth-century English natural philosophers such as Robert Boyle, Robert Hooke, Nehemliah Grew and Robert Plot attributed the phenomenon of color in the natural world to salts and saline chymistry. They rejected Aristotelian ideas that color was related to the object's hot and cold qualities, positing instead that saline principles governed color and color changes in flora, fauna and minerals. In our study, we also characterize to what extent chymistry was a basic analytical tool for seventeenth century English natural historians. PMID- 26856052 TI - [The death of Yasser Arafat: molecular-genetic authentication of the remains as an indispensable condition for the evaluation of the medical hypotheses of the cause of his death]. AB - The objective of the present study was the molecular-genetic authentication of the remains as an indispensable condition for the evaluation of the medical hypotheses of the cause of death in 2004 of Yasser Arafat, the former Palestinian leader and the first president of the Palestinian National Administration, the Nobel Peace Prize laureate. We carried out molecular-genetic investigations aimed at establishing the circumstances and cause of the death of Yasser Arafat including the analysis of the relevant medical documentation, the examination of the burial place at Ramallah, remains, and personal belongings stored in his Al Muqata'ah residence at Ramallah. The objective of the present molecular- genetic investigations was to confirm the authenticity of the fragments of Yasser Arafat's remains available for radio-toxicological, chemical toxicological, and other laboratory studies. The reference objects were the contact traces left on the personal belongings by their owner. The aggregate probabilistic estimate of the coincidence of genotype traits of autosomal DNA, Y-chromosomal DNA, and mtDNA was at least 99,(9)29 4% which gives evidence of the genetic identity of the objects of study. It is this value (99.999999 <...> 9999999(29) 4%) that characterizes the probability that the bone fragments provided for the laboratory studies are actually authentic remains of Yasser Arafat. PMID- 26856053 TI - [Polonium-210 acute and chronic pathomorphology and pathogenesis]. AB - In the present review, the data on the pathology of acute and chronic polonium injuries available from the an open-access domestic and foreign literature are primarily systemized and analyzed. The historical background of the research is presented in brief. On the basis of clinical and experimental generalizations, the current concept regarding the pathogenesis of polonium intoxication has been developed. PMID- 26856054 TI - [The role of the biological damaging factor in the explosive injury]. AB - This article describes the specific features of the action of the biological damaging factors on the human organism associated with the explosive injury. Both the direct action of the damaging agents contained in the biological weapons and their secondary effects in the form of systemic and local infectious complications of the inflicted wounds are considered. The criteria for the evaluation of the degree of harm to the health of the victims of explosion attributable to the action of the biological damaging factor are proposed. PMID- 26856055 TI - [The forensic medical evaluation of the injuries to the cervical spine in the driver and the front-seat passenger of a modern motor vehicle after the frontal crash]. AB - The objective of the present study was to elucidate the specific features of the lesions of the cervical spine in the driver and the front-seat passenger of a modern car after the frontal crash. We made use of the archival materials of forensic medical expertises concerning the traffic accidents carried out in the city of Moscow during the period from 2005 to 2012. The study was focused on the analysis of the character of the fractures of cervical vertebrae in the drivers (n = 55) and the front-seat passengers (n = 85) of a modern motor vehicle involved in a traffic accident. It was shown that the drivers most frequently suffer bending-extension fractures of the cervical vertebrae, with the II-IV vertebrae being especially frequently subject to multiple fractures resulting in the damage to the anterior support column, sometimes to both the anterior and posterior columns, and much rarer to the posterior column. The front-seat passengers also suffer bending-extension fractures. The IV-VI vertebrae are most frequently affected in them with isolated damages to either the anterior or the posterior support column of the neck vertebrae. PMID- 26856056 TI - [The peculiarities of deposition of foreign particles in the skin region experimentally damaged by the electrical saw cutting element]. AB - The objective of the present study was to detect the deposition of foreign particles and other introduced objects in the human skin region damaged by the electrical saw cutting elements and to use the data thus obtained for the estimation of the speed and the type of the instrument, the main characteristics of the cutter covering and/or composition of its surface. The experiments included the sawing of the skin fragments using the small steel saws differing in the type of the surface cover, such as the uncoated (steel), stained, nickel- or chromium-plated, blue-finished saws with the movement speed of the cutting element 500, 1000, 2500, 2,000, and 3,000 revolutions per minute. The study provided information about the peculiarities of deposition of foreign particles and other introduced objects in the damaged regions of the human skin that allow not only to establish the fact of using the electrical saw with a high-speed back and-forth movements of the cutting element but also the type of the instrument and the main characteristics of its cover and/or the composition of its surface. PMID- 26856057 TI - [The modern approaches to the determination of the content of elemental impurities in the pharmaceutical substances with the use of inductively-coupled plasma mass-spectrometry]. AB - The elemental impurities contained in the composition of the pharmaceutical dose forms are known to be capable of interacting with their active substances and excipients and of catalyzing their degradation; thereby, they alter stability of the drug products and exert toxic effects on the human tissues. The present publication was designed to report the results of the purity tests for ascorbic acid, valine, and galactose substances by inductively-coupled plasma mass spectrometry (IBP-MS). This method is recommended for use by the US and EU pharmacopoeias and for the replacement of the traditional test for heavy metals with the use of PbS ethanol suspension. PMID- 26856058 TI - [Investigations of the distribution of aripiprazole in the internal organs and biological fluids of the laboratory animals in case of acute intoxication]. AB - Despite the present-day extensive application of aripiprazole, there are many cases of its overdose and of poisoning with this compound. The objective of the present study was to detect and quantify aripiprazole in the internal organs and biological fluids of the laboratory animals in case of acute intoxication. The experiments were carried out on white mice of both sexes weighing 20.5 and 25.7 g. Aripiprazole was isolated from the liver, kidneys, brain, and heart as described by A.A. Vasil'eva and from the plasma and urine by the newly developed original methods. Aripiprazole was identified and quantitatively determined in the extracts from the aforementioned organs and tissues with the use of HPLC. The data obtained on the completeness of extraction from the liver, kidneys , and brain of the laboratory animals indicate that aripiprazole accumulated in the highest concentrations in the brain and kidneys within 24 hours after acute poisoning. Ist content was significantly lower in the liver while no traces of aripiprazole were found in the heart of the mice. The methods for aripiprazole isolation from the urine and blood plasma are described. The maximum amounts of aripiprazole were detected in blood plasma within 24 hours after acute intoxication. It is concluded that the proposed methods for aripiprazole isolation from the biological fluids (blood plasma and urine) can be included in the scheme of the chemical toxicological analysis of this compound. PMID- 26856059 TI - [The forensic chemical investigation of acetylsalicylic acid]. AB - The objective of the present study was to develop the universal approach to the quantitative determination of acetylsalicylic acid in biological tissues and fluids to be applied in the practice of forensic chemical expertise with the use of thin-layer chromatography, gas chromatography and mass spectrometry, low pressure column chromatography, and spectrophotometry. A system of solvents consisting of acetone and ethyl acetate (7:3) was proposed as a universal agent for extracting acetylsalicylic acid from the cadaveric tissues and blood. It was shown that acetylsalicylic acid and its principal metabolite, salicylic acid, can be purified from the endogenous admixtures present in the biological materials by column chromatography on silica gel L 40/100 mcm. Salicylic acid in extracts from biological materials was identified and quantified with the use of thin-layer chromatography, gas chromatography/mass spectrometry, and electronic spectrophotometry. The method for forensic chemical investigation of acetylsalicylic acid has been developed and applied in the analysis of the material provided for expertise. PMID- 26856060 TI - [Amniotic fluid embolism as a cause of maternal death]. AB - This article reports the case of death of a puerperal woman resulting from amniotic fluid embolism. The diagnosis was established based on the results of the pathohistological study that revealed the presence of mucoproteides and epithelial scales in pulmonary blood vessels and capillaries. PMID- 26856061 TI - [The expert observation of myocardial contusion in a child]. AB - A case of the myocardial contusion associated with the closed blunt chest injury in the girl aged 1 year 7 months is presented. The autopsy revealed hemorrhage of an irregular oval shape, coloured dark-red, and confined to the region with the area of 4.0 x 3.5 cm. It penetrated throughout the entire thickness of the lower part of the left atrial myocardium and the upper and middle parts of the left ventricle. No other changes were found in the heart, nor were congenital cardiac and vascular malformations documented. The main factors playing an important role in the formation of the myocardium contusion are discussed. The authors emphasize that it is the children having the narrow chest with the pliable wall who constitute the group at the highest risk of accidents resulting in the chest injury and myocardial contusion. PMID- 26856062 TI - [The peculiarities and prospects of the investigations of ptomaines for the purpose of forensic medical analysis]. AB - This review of the literature presents the results of analysis of the publications concerning the prospects of the investigations of ptomaines including their influence on the results of determination of toxic substances present in the putrescent cadaveric tissues and on the persistence of analytes in the biological materials. Special emphasis is laid on the peculiarities of investigation of ptomaines and the necessity of the further development of the methods for the detection, isolation, and identification of toxicants in the putrescent and exhumed biological objects bearing in mind that such studies are not infrequently provide the sole opportunity to prove intoxication with certain substances. PMID- 26856063 TI - [The historical aspects of the notion of "self-striking" in the Russian- and foreign-language literature]. AB - This article was designed to illustrate specific features of the injuries inflicted by the sharp objects as a result of the so-called self-striking based on the examples from the historical and literary works. The forensic medical characteristics of such cases are provided. PMID- 26856064 TI - [In memory of Evgeniy Mikhailovich Salomatin]. PMID- 26856066 TI - Giving Light to Narrative. The Use of Images in Early Modern Learned Journals. AB - This paper examines the visual and verbal cross-pollination between the Philosophical Transactions and the Journal des Scavans with a specific focus on the role of the visual as an open form of communication, which overcame the linguistic barriers implied by journals published in vernacular languages, rather than Latin. Studying the illustrated articles published in the two journals in 1666 highlights the ways in which the authors viewed the images as providing clarity to their prose and how the images provided access to useful information that was otherwise invisible. PMID- 26856065 TI - Visual Communication: From the Learned to the Scientific Periodical. PMID- 26856067 TI - Illustrating Pathologies in the First Years of the Miscellanea Curiosa, 1670 1687. AB - The Miscellanea Curiosa, sive Ephemeridum Medico-Physicarum Germanicarum, the learned periodical published in different German cities under the aegis of the Academia Leopoldina Naturae Curiosorum, contained many cases of an anatomical nature. The Miscellanea Curiosa in its first years actively participated in the development of anatomia practica, the anatomical practice of observing the signs of diseases in cadavers and connecting them to what had been observed at the bedside. The illustrations that accompanied the post-mortem reports published in the Miscellanea Curiosa allow one to assess the evolution of the pathological illustration itself. This article is thus intended to serve as a contribution to the rediscovery of the origins of this visual genre. A learned journal like the Miscellanea Curiosa, which appeared regularly, provided an ideal venue for the process of accumulating, cross-referencing and--in the final analysis--selecting, serializing and systematizing the knowledge that would form the foundations of modern pathology, by providing a wealth of evidence and images observed at the dissection table. PMID- 26856068 TI - Authoritative Images. The Kiwi and the Transactions of the Zoological Society of London. AB - The first exemplar of a kiwi, the wingless bird of New Zealand, arrived in the form of a lifeless specimen in Europe in 1812. A debate was sparked over the appearance and nature of this strange creature and indeed whether it actually existed. In 1833 the Transactions of the Zoological Society of London entered the debate and the illustrations published in this journal contributed greatly to the acceptance and further study of the kiwi. Some of the most eminent British zoologists and anatomists of the time were involved, from William Yarrell to Richard Owen, and from John Gould to Abraham Dee Bartlett. This crucial period in the discussion, which would extend over two decades and would only be brought to a close with the arrival of the first living specimen in the London Zoological Garden in 1851, will be analyzed based on a detailed examination of the reports published in the Transactions and other journals. This essay will show how images of the bird were produced and used by zoologists during different stages in the early research on the bird and how these figures circulated inside and outside the zoologists' community. PMID- 26856069 TI - Travelling Scientist, Circulating Images and the Making of the Modern Scientific Journal. AB - The early astrophysicist Norman Lockyer was both editor of the journal Nature from its creation in 1869 and for the following five decades, and an early practioner of the new astronomy. He frequently used the journal to expound his scientific theories, report on his work and send news home while on expeditions. I look into the particular visual culture of astrophysics developed by Lockyer in Nature, its evolution at a time of rapid development both of the techniques of astrophysical observation and visualization and of the techniques of image reproduction in print. A study of the use and reuse of visual materials in different settings also makes it possible to sketch the circulating economy of Lockyer's images and the ways in which he put himself forward as a scientist, at a time when he was advocating the State support of research and scientists and helping create the modern scientific journal. PMID- 26856070 TI - [PROSPECTS OF THE NUCLEAR PROTEIN NeuN APPLICATION AS AN INDEX OF FUNCTIONAL STATE OF THE VERTEBRATE NERVE CELLS]. AB - Assessment of safety, viability, and functional state of nerve cells is the major problem in studies of experimental effects on various structures of vertebrate brain and in search for correlation between structural abnormalities and changes in physiological parameters. Such an assessment is possible with applying an immunocytochemical reaction to neuronal nuclear antigen NeuN discovered in 1992. Numerous studies of the protein showed its neural specificity and its amino acid consequence was found to have high interspecies concervatism. This review summarizes and analyzes the available data about the function of the NeuN protein in nerve cells and the results of using this marker for assessment of functional state and viability of CNS neurons in experiments. Particular attention is paid to. the critical analysis of the basic data used for the conclusions on the properties and functions of NeuN. It is stated that there are no satisfactory explanation for lacking the constitutive expression of this marker in some neuronal populations of the mammalian brain and spinal cord. The analysis of our own and literature data presented in the review suggests the future prospects of NeuN labeling for investigation of nerve cell responses to damage including comparative interspecies studies. Key words: brain, neuron, immunocytochemistry, neuronal protein NeuN, vertebrates. PMID- 26856071 TI - [CATALITICAL PROPERTIES OF LIVER MONOAMINE OXIDASE IN THE CHUM SALMON ONCORHYNCHUS KETA]. AB - The substrate and inhibitory specificity of mitochondrial monoamine oxidase (MAO) in the liver of males of the summer form of the chum salmon Oncorhynchus keta was studied. As to the spectrum of deaminated substrates, the hepatic MAO of the chum salmon is similar to MAO of most terrestrial mammals, for eight classical MAO substrates similarity in their substrate characteristics were found. Analysis of the antimonoamine oxidase activity of two derivaties of 2-propinilamine, five derivatives of acridine as well as of pyronine G revealed significant qualitative and quantitative differences as compared to the hepatic enzyme of tuna and whitefish. The compounds tested manifested themselves as irreversible inhibitors of chum salmon's hepatic MAO possessing various efficacy, but lacking the selectivity of action as dependent on the deaminated substrate. The obtained data on the substrate and inhibitory analysis provide an indirect evidence for the presence of a single molecular form of MAO in the chum salmon liver. PMID- 26856072 TI - [BIOCHEMICAL RESPONSE OF BLUE MUSSELS MYTILUS EDULIS L. FROM THE WHITE SEA TO RAPID TEMPERATURE CHANGES]. AB - The effect of a rapid temperature change on the biochemical status of blue mussels Mytilus edulis L. from the White Sea was studied under conditions of aquarium experiment. It is shown that modifications of the composition of reserve and structural lipids and their fatty acids, of the activity of lysosomal enzymes (beta-glucosidases, cathepsins B and D), of calcium-dependent proteases of cytocol (calpains) and of the enzyme of the second phase of biotransformation of xenobiotics - glutathione-S-transferase, reflect an unspecific compensatory reaction of bivalves to stress action of environmental factors and indicate reconstruction of blue mussel metabolism as early as within first hours of temperature change. The initial high level of glutathione-S-transferase activity in control blue mussels as well as an increase of glutathione concentration in the course of experiment may facilitate successful exit of mussels from the state of reduced metabolism. PMID- 26856073 TI - [IDENTIFICATION OF THE CHARACTERISTICS OF SPONTANEOUS ELECTRICAL ACTIVITY IN THE MYOMETRIAL RHYTHMOGENIC AREAS IN RATS]. AB - Spontaneous bursts of action potential occurring in the ovarian and cervical horn areas as well as in uterine corpus were investigated in non-pregnant rats. The main characteristics of spikes registered simultaneously from the selected active regions under normal conditions - the frequency, amplitude, rise-rate, rise-time and half-width of peaks, were analyzed by complex electrophysiological and morpho histochemical studies. The ovarian horn area generates high-amplitude spikes that significantly exceed the magnitude of spikes in two other areas. There are small differences between the frequency values in the above-mentioned rhythmogenic areas. The peak rise-rates are the greatest in the ovarian horn area. On the contary, the peak rise-times and the peak half-widths had the smalles values here. It is concluded that there is a significant difference between the values of activity parameters in the ovarian horn area and two other pacemaker areas localized rather close to each other. Analysis of the morphological and histochemical data revealed the greatest aggregation of functionally active cells between the myometrium and serosa in the ovarian horn area. In the cervical horn area and uterine corpus no focal accumulations of these cells were found. Thus, the morphological findings confirmed the electrophysiological results. PMID- 26856074 TI - [GLUCOSE CONTENT FLUCTUATION IN BLOOD OF NEWBORN RATS DEPENDING ON SEASON AND PATTERN OF SPONTANEOUS MOTOR ACTIVITY]. AB - Earlier we have shown that in newborn rats the glucose level in blood serum changes depending on the pattern of spontaneous periodic motor activity (SPMA). During rest periods, both under dominant decasecond rhythm and under dominant minute rhythm, the glucose level in blood serum is higher than during activity periods. We have also shown that the glucose level in the blood serum rises with age reaching the level of adult animals by day 10. In the present study carried out on 3-10-day-old rats under conditions of free behavior the blood glucose content was investigated in different periods of <> cycle during different seasons. It is found that in newborn rats of all ages studied (3-, 5-, 7-, and 10-day-old ones) the lowest glucose concentration in the blood is observed in the winter period. In spring its level increases and in summer reaches the maximum different significantly from the winter and spring levels in all age groups except day 5. In autumn the glucose level decreases and approaches the spring values but it is still different from the winter indices. In 5-day-old rats statistically significant differences of glucose levels in different seasons were not observed. The data obtained provide evidence of seasonal fluctuations of the glucose level in blood serum of newborn rats. At the same time during all seasons except spring the dependence of glucose level on the pattern of motor activity persists. In spring these differences are smoothed. Key words: ontogenesis, motor activity, metabolic factors, glucose, seasonal variations. PMID- 26856075 TI - [NEUROPHYSIOLOGIC APPROACHES TO THE STUDY OF FUNCTIONAL ROLE OF THE AUDITORY CRITICAL BANDS]. AB - Neurophysiologic data on participation of the critical band mechanism in sound localization and recognition are presented. Single unit activity was recorded extracellularly-in the central nucleus of inferior colliculus of the house mouse females. First, we studied sensitivity of neurons to acoustic signals simulating spectral localization cues (notch noise with different bandwidths). Comparison of neuron responses depending on notch bandwidths revealed that 1/3 octave notch bandwidths was optimal for the analysis of the localization-significant spectral information. This notch bandwidths corresponded to the critical bandwidths of the auditory midbrain neurons evaluated earlier by the simultaneous masking paradigm. Second, we studied selectivity of neuronal responses to the mouse pups' wriggling call, a set of its models and frequency components. The data obtained showed that models of wriggling call frequency components, located as in natural call, in three non-overlapping critical bands produced stronger neuronal responses than other models. We assume that our finding proves the universal role of the critical bands mechanism in processing different parameters of acoustic stimuli. Key words: inferior colliculus, auditory critical bands, sound source localization, analysis of bioacoustic signals. PMID- 26856076 TI - [QUANTITATIVE ASSESSMENT OF THE RELATIONSHIP BETWEEN SLOW-WAVE OSCILLATIONS OF HEART RHYTHM AND MOTOR ACTIVITY IN RAT FETUSES WITH FEMALE RESPIRATORY AND CARDIAC ACTIVITY]. AB - A mathematical analysis of correlation of slow-wave processes in the system <> during the last 4 days of bearing was performed in experiments on rat fetuses with retained placental connection with the female. The parallel recording of physiological indicators of the female and fetus state revealed the existence of a relationship between oscillations of heartbeat rhythms and breathing in about-one-minute and many-minute ranges. The highest values of connection between the heart rhythms of female and fetus are characteristic for days 17 and 20 of gestation. On day 18-19 the interrelationships are slightly weaker. The specific mechanism providing this synchronization between heartbeat oscillations of mother and fetus is unclear. There are two hypothetic possibilities: an oscillation driver close in parameters for mother and fetus, and the maternal rhythm directly affecting the fetus. PMID- 26856077 TI - [MORPHOLOGICAL BASES OF REORGANIZATION OF THE RAT CEREBELLAR CORTEX IN SENESCENCE]. AB - A histological and immunohistochemical study of the cerebellar cortex of senescent Wistar rats (36-month-old) was performed in comparison to young rats (36-month-old).The cerebellar cortex of senescent animals typically showed degeneration of the Purkinje cells accompanied by immunochemically determined loss of the calcium-binding protein calbindin. These results suggest that presence of calbindin in the Purkinje cells is a criterion of functional activity of these neurons. The Purkinje cells degeneration is accompanied by lesion of the synaptophysin-containing basket cell networks, which is an indication of impaired function of inhibitory (GABAergic) axo-axonal synapses. During senescence significant rear-rangement is observed in the glomeruli of the granular layer of the cerebellum, which are the structures where primary afferent animals disintegrate suggesting of alteration in the transmission of information from the cerebrum to the cerebellum. PMID- 26856078 TI - [REACTION OF STRUCTURAL ELEMENTS OF HEMATOENCEPHALIC BARRIER IN NEWBORN RATS TO NORMOBARIC HYPOXIA]. AB - For the last time a particular interest of investigators has been attracted to the period of early newborn state when active process of adaptation of the organism to new life conditions occur defining its increased sensitivity to the effect of unfavorable environmental factors. An important place among these processes belongs to formation of homeostasis mechanisms and, primarily, the barrier mechanisms. The purpose of the present study was to investigate reactions of the hematoencephalic barrier (HEB) to action of perinatal normobaric hypoxia (a model of incomplete human pregnancy). Using light and electron microscopy, our investigation showed that after action of hypoxia all wall elements of neocortex capillaries revealed structural alterations which may cause impairment of microcirculation and increased permeability of HEB. It is established that differentiation of the basal membrane of a capillary wall takes place during the early perinatal period and the indicator of its differentiation is the formation of its plates - laminae rara et densa. After action of hypoxia, besides a delay of formation of the basal membrane, a vesicular type of its degeneration occurs. Key words: perinatal hypoxia, hematoencephalic barrier, capillary, endothelial cells, basal membrane. PMID- 26856079 TI - [PROINSULIN C-PEPTIDE AND ITS C-TERMINAL FRAGMENTS STIMULATE Gi/o-PROTEINS BUT DO NOT INFLUENCE ADENYLYL CYCLASE ACTIVITY]. PMID- 26856080 TI - [KINETIC PROPERTIES OF PYRUVATE DEHYDROGENASE AND 2-OXOGLUTARATE DEHYDROGENASE COMPLEXES FROM A NEW SOURCE - THE HEART OF WILD BOAR SUS SCROFA]. PMID- 26856081 TI - [ELIE METCHNIKOFF--THE FOUNDER OF LONGEVITY SCIENCE AND A FOUNDER OF MODERN MEDICINE: IN HONOR OF THE 170TH ANNIVERSARY]. AB - The years 2015-2016 mark a double anniversary--the 170th anniversary of birth and the 100th anni- versary of death--of one of the greatest Russian scientists, a person that may be considered a founding figure of modern immunology, aging and longevity science--Elie Metchnikoff (May 15, 1845-July 15, 1916). At this time of the rapid aging of the world population and the rapid development of technologies that may ameliorate degenerative aging processes, Metchnikoff's pioneering contribution to the search for anti-aging and healthspan-extending means needs to be recalled and honored. PMID- 26856082 TI - [CHANGING OF THE MORPHOMETRIC AND CYTOLOGICAL INDEXES OF THE SPLEEN IN THE CONDITION OF ACUTE BLOOD LOSS ON THE BACKGROUND OF STEM CELLS INSERTION]. AB - The objective of the work was to study morphometric and cytological indexes of the spleen in mature and old laboratory animals after acute blood loss on the background of allogenic transplantation of placenta MMSC and GSC. The study proved that 5 days after acute blood loss on the background of stem cells transplantations to the mature animals there was a reduction of lymphoid follicles area due to reduction in thymus independent area. There were no immunosuppressive effects to the white pulp of the spleen in old animals. The increase of leucocytes' and erythrocytes' elements in red pulp in the mature animals was noted. In old animals, the increase of cells' density in red pulp is mainly due to increased number of erythroid cells. PMID- 26856083 TI - [MATRIX METALLOPROTEINASE 9 AND TISSUE INHIBITOR OF MATRIX METALLOPROTEINASES TYPE 1 SERUM CONCENTRATIONS AND GENETIC POLYMORPHISM IN SENILE AORTIC STENOSIS]. AB - The study of the serum levels of matrix metalloproteinase 9 (MMP9) and tissue inhibitor of matrix metalloproteinases type 1 (TIMP1) was conducted involving 108 patients aged over 65, with calcinosis and/or calcific aortic valve (AV) stenosis. The purpose of the study was to identify the molecular and genetic markers responsible for the development of senile aortic stenosis. Besides, there was also typing of polymorphic loci of MMP9 gene A8202G (rs1169732) and TIMP1 gene C536T(rs11551797) performed. The comparison group included 46 patients whose examination revealed no evidence of AV calcinosis present in them. Association of senile aortic stenosis with a significant increase in the serum TIMP1 levels (257,5 (151,5-325,9) pg/ml vs 129,7 (86,2-229) pg/ml, p < 0.05) has been detected, while the TIMP1 concentration going beyond 258,1 pg/ml in the elderly people over 65 years can be considered as a high-precision marker of the pathology under discussion. The MMP9 (A8208G) as well as TIMP1 (C5367) genetic polymorphisms are not associated with calcific aortic stenosis. PMID- 26856084 TI - GENETICS OF HUMAN AGE RELATED DISORDERS. AB - Aging is an inevitable biological phenomenon. The incidence of age related disorders (ARDs) such as cardiovascular diseases, cancer, arthritis, dementia, osteoporosis, diabetes, neurodegenerative diseases increase rapidly with aging. ARDs are becoming a key social and economic trouble for the world's elderly population (above 60 years), which is expected to reach 2 billion by 2050. Advancement in understanding of genetic associations, particularly through genome wide association studies (GWAS), has revealed a substantial contribution of genes to human aging and ARDs. In this review, we have focused on the recent understanding of the extent to which genetic predisposition may influence the aging process. Further analysis of the genetic association studies through pathway analysis several genes associated with multiple ARDs have been highlighted such as apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), cadherin 13 (CDH13), CDK5 regulatory subunit associated protein 1 (CDKAL 1), methylenetetrahydrofolate reductase (MTHFR), disrupted in schizophrenia 1 (DISC1), nitric oxide synthase 3 (NOS3), paraoxonase 1 (PON1), indicating that these genes could play a pivotal role in ARD causation. These genes were found to be significantly enriched in Jak-STAT signalling pathway, asthma and allograft rejection. Further, interleukin-6 (IL-6), insulin (INS), vascular endothelial growth factor A (VEGFA), estrogen receptor1 (ESR1), transforming growth factor, beta 1(TGFB1) and calmodulin 1 (CALM1) were found to be highly interconnected in network analysis. We believe that extensive research on the presence of common genetic variants among various ARDs may facilitate scientists to understand the biology behind ARDs causation. PMID- 26856086 TI - [TEMPORAL ORDER DETERIORATION AND CIRCADIAN DISRUPTION WITH AGE]. AB - The present review summarizes the current knowledge of gradual deterioration of temporal order in aging humans and other mammals. An obvious consequence of age dependent circadian disruption in complex mechanisms is extra-circadian dissemination (ECD) that can be observed in overt rhythmic functions. ECD is a variance transposition from circadian to ultradian and infradian frequencies accompanied by a loss of interdaily phase stability. Moreover, heterochronic changes in central and peripheral tissue-specific cellular mechanisms are involved in circadian desychronization. A multitude of internal factors accounts for cumulative clockwork misalignment. Age-related circadian disruption is a consequence of weaker rhythm generation and the loss of proper orchestration on molecular, tissue and systemic levels, disabling their circadian synchrony and resonance. PMID- 26856085 TI - [VARIOUS ALLELES OF HSF HEAT-SHOCK TRANSCRIPTION FACTOR OF DROSOPHILA MELANOGASTER INCREASE VIABILITY OF ITS CARRIERS IN UNFAVORABLE ENVIRONMENTS]. AB - We found increased viability in heterozygous carriers of hsf heat shock transcription factor n comparison with wild type. The effect depends on temperature, sex and direction of crosses. Viability effect is more evident in conditions of soft temperature stress. The males are more sensitive. The maternal effect is observed: if hsf*allele came from mother, the viability effect is stronger. The survival curves of heterozygotes on hsf-1 and hsf-4 alleles are similar in spite of HSF-4 protein is slightly active on normal temperature. PMID- 26856087 TI - [STRESS- AND GERO PROTECTIVE PROPERTIES OF 20-HYDROXYECDYSONE AND ITS DERIVATIVES]. AB - The long-term stress protective effects have been revealed among newly synthesized 9alpha-hydroxy-5alpha-ecdysteroids via a short-term heat stress tests (housefly Musca domestica). An increase as well as a reduce of protective effects for synthesized compounds have been demonstrated in comparison with the reference ecdysteroid 20-hydroxyecdysone, which obtained from the juice of Serratula coronata. The interdependence between stress- and geroprotective properties of the test models with their genotypic features and the structure of ecdvsteroids has been established. PMID- 26856088 TI - [AGING AND OSTEOARTHRITIS. CHRONIC NONSPECIFIC INFLAMMATION AS A LINK BETWEEN AGING AND OSTEOARTHRITIS (REVIEW)]. AB - This article presents review on the processes underlying aging and the most common age-associated diseases. Special attention is given to the role of chronic nonspecific inflammation. Based on the literature data it was demonstrated that aging and osteoarthritis have the same basic molecular and cellular mechanisms, among which general are cascades intracellular transcription chronic nonspecific inflammation and metabolic disturbances plays an important role. It is concluded that the process of normal aging is not a disease, but makes the human body, and particularly the musculoskeletal system, susceptible to age-associated changes. Number of changes in the human body that accompany the aging process, and play a role in the development and progression of OA, are potentially reversible, regardless of age (eg, chronic non-specific inflammation), and can be considered as a possible entry points for the effective prevention and complex therapy of OA in elderly people. PMID- 26856089 TI - [FEATURES OF OXIDATIVE STRESS IN THE BLOOD AND THE SYNOVIAL FLUID ASSOCIATED WITH KNEE OSTEOARTHRITIS]. AB - The features of regulation of free radical oxidation in the blood and the synovial fluid have been studied in patients with knee osteoarthritis. The data were obtained from 46 patients with primary knee osteoarthritis (II-III Kellgren Lawrence grade, aged 63.26 +/- 9.18) and 27 healthy controls. It was defined that the blood plasma was characterized by increased superoxide-eliminating activity and a tendency to the increasing of nitrite/nitrate concentration (nitrosative stress biomarkers). The erythrocytes were measured to have the increased concentration of malondialdehyde (secondary product of lipid peroxidation), activation of superoxide dismutase, gIutathione-S-transferase and reduced glutathione peroxidase activity and glutathione content. The peripheral blood mononuclear fraction of patients with osteoarthritis was characterized by significant activation of superoxide dismutase and glutathione-S- transferase, moderate catalase activation, non-significant glutathione peroxidase activity alterations and increased activity of xanthine oxidoreductase and myeloperoxidase. Finally redox-balance disturbance in the mononuclear cells leaded to oxidative stress development, which promoted lymphocytes apoptosis. PMID- 26856090 TI - [FEATURES OF INTERRELATIONS OF HOMEOSTATIC SYSTEMS AS INDICATORS OF ADAPTIVE REORGANIZATIONS IN ELDERLY]. AB - The aging process is characterized by progressive limitation of the adaptive capacities of the organism determining the level of human health. The analysis of the functioning systems involved in the adaptation of structural and functional modifications of the-body, is one of the important areas of the research in the medicine. Investigation of mechanisms of adaptive reactions is possible on the basis of an assessment of the correlation of the relationship of homeostatic functions of various body systems. A number of clinical studies during the last decades showed ontogenetic variability of the lipid spectrum of cell membranes, immune, lipid peroxidation-antioxidant protection systems, blood system, involved in the adaptation of the underlying cellular and molecular levels. The relationship of some homeostatic systems during physiological aging was investigated. We found the increase in the amount of intersystem relationship, the power of intersystem and intrasystem relationship. The observed complexity of structural and functional interactions, of homeostatic systems of the aging body indicates age-dependent cooperative systems, aimed at preserving the relationships between them, and a smaller balance of adaptive reactions in the elderly. The study of the nature of intersystem and intrasystem integrations with age aspects allowed showing the adaptive strategy of an aging organism, aimed at preserving its functional integrity. PMID- 26856091 TI - [IMMUNE PARAMETERS OF SALIVA IN PERSONS OF DIFFERENT AGE RESIDING IN ST. PETERSBURG AND LENINGRAD REGION]. AB - The article presents the estimation of indicators of saliva secretory immunity in 109 people of different ages (22-90 years) residing in St. Petersburg and the Leningrad region, with no diseases of the salivary glands. The content in saliva IgA, IgM, IgG and secretory IgA, and pro-inflammatory (IL-1beta, IL-6, IL-8, TNF alpha) and anti-inflammatory (IL-1 receptor antagonist, IL-4, IL-10) cytokines was studied by ELISA. The study established that the level of sgA in saliva increases with age, reaching maximum values in a group of elderly people, but content of sIgA in saliva was falling in people of senile age. In patients of elderly and senile age we also observed changes in the content of cytokines in saliva: increased levels of proinflammatory IL-1beta and TNF-alpha and anti-IL 10, with a simultaneous decrease of IL-8 (the main chemotactic factor for neutrophils). These changes may cause an imbalance in the local immune response to the pathogen and development of both autoimmune and inflammatory diseases of the oral cavity. PMID- 26856092 TI - [GENETIC AND EPIGENETIC DETERMINANTS OF ALZHEIMER'S DISEASE]. AB - Alzheimer's disease (AD) is one of the most important economic, medical and social problems in modern society. Numerous studies have highlighted the role of genetic and epigenetic factors in this disease. Increased risk of AD is associated with certain polymorphic variants of the APOE gene, as well as some other, less affecting genes. In the review, recent studies demonstrating the role of genetic and epigenetic factors in the etiology and pathogenesis of AD are discussed. PMID- 26856094 TI - [ASSESSMENT OF ENERGY NEEDS AND THE ROLE OF NUTRITIONAL SUPPORT IN SENILE PATIENTS WITH INTESTINAL FAILURE IN ORTHOPEDIC SURGERY OF HIGH RISK]. AB - The study of anamnestic, clinical, laboratory, endoscopic, morphological parallels of senile patients in knee and hip joints prosthesis shows the presence of intestinal failure while perioperative period. A direct connection between a natural intestinal and immune dysfunction and nutritional deficiency was diagnosed. The use of nutritional-metabolic correction of comorbid pathology and determination of basal metabolism in the perioperative period enabled to normalize indicators of homeostasis, microflora of the colon, indicators of immune status, and get a reduction in the number of early postoperative complications. PMID- 26856093 TI - [CAROTID STENTING EXPERIENCE IN THE ACUTE PHASE OF ISCHEMIC STROKE IN PATIENTS OF ELDERLY AND SENILE AGE]. AB - Age has been shown to be a predictor of neurological complications during carotid stenting (CS). However, carotid stenting in acute period of ischemic stroke has recently been demonstrated safely in patients over 70 and even 80 years. Early intervention is desirable in patients presenting with stroke referable to carotid artery stenosis because of the high incidence of recurrent ischemic events. However, he optimal timing to perform CS in the acute phase of ischemic stroke in elderly remains unclear due to the threat of perioperative complications. In our hospital (Aleksandrovskaya) was searched for consecutive cases of extracranial internal CS procedures performed for symptomatic atherosclerotic carotid stenosis in the acute phase of ischemic stroke in a total of 65 elderly patients. The primary outcome was not statistically different among groups stratified based on intervention timing, with a combined incidence of stroke, MI or death of 5.9 % in patients treated within 2 days, 0% in patients treated between days 3 and 7, 15% in patients treated between days 8 and 14 and 0% in patients treated between days 15 and 30. Our results support the conclusion that early CS (within 2 days) carries no additional risks compared with CAS after 2 days or any other timing of the intervention up to 30 days in elderly. PMID- 26856095 TI - [PLATELET AGGREGATION IN CLINICALLY HEALTHY PERSONS OF THE SECOND COMING OF AGE LIVING IN THE KURSK REGION]. AB - This work is dedicated to the study of the aggregation of platelet activity in healthy persons the second coming of age. The study group included 146 clinically healthy people of the second coming of age, leading a healthy lifestyle and not having metabolic and cardiovascular diseases. In healthy people of 36-45 years noted the lack of reliable antioxidant dynamics of platelets and levels of lipid peroxidation. Platelet aggregation with a range of inductors in people of 36-60 years confirmed the age-dependent increase of aggregation platelet function. After 45 years of age, the activity of platelet aggregative in healthy people increases gradually, leading to an increase in their blood platelet active forms, which inevitably leads to the increase in the number of circulating units of various sizes. This tendency is accompanied by painful with age, increasing negative impact of environmental factors, contributing to the realization of a genetic predisposition to various, primarily cardiovascular, diseases. PMID- 26856096 TI - [DYNAMICS OF TWENTY-FOUR HOUR MONITORING OF BLOOD PRESSURE IN ELDERLY PATIENTS WITH BRONCHIAL ASTHMA]. AB - Twenty-four hour blood pressure monitoring in groups of patients of elderly age with bronchial asthma and hypertension was conducted. The study showed an increased variability of blood pressure and insufficient reduction in night time that leads to development of cardiovascular complications. PMID- 26856097 TI - [PSYCHO PHYSIOLOGICAL MARKERS OF ACCELERATED AGING AMONG THOSE WORKING WITH OCCUPATIONAL HAZARDS]. AB - Using comparative analysis of two occupational groups we assessed the significance of psycho physiological markers of short-term memory accelerated aging in order to reveal how the age-related changes and working process affect mental work capacity. We revealed peculiarities of systemic structure of functions which determine mental work capacity depending on the age and length of service in lorry drivers. It was proved that age and long driving experience affect mnestic functions which show up quantitative and qualitative changes such as reduced volume of memorized information, longer time needed to memorize it, and tendency to diminished accuracy of memorization. We also proved that premature age-related changes of psycho physiological indices in drivers are the "risk indicators", while long driving experience is a real risk factor contributing to the acceleration of aging. PMID- 26856098 TI - [PSYCHO PHYSIOLOGICAL MARKERS OF ACCELERATED AGING AMONG THOSE WORKING WITH OCCUPATIONAL HAZARDS]. AB - We assessed the significance of psycho physiological markers of accelerated aging of the function of attention using comparative analysis of two occupational groups in order to reveal how the working process affects mental work capacity. We revealed peculiarities of systemic structure of functions which determine mental work capacity depending on the age and length of service in lorry drivers. It was proved that decrease in the mnestic functions of lorry-drivers takes place 10-15 years earlier compared to the control group. Psycho physiological indices, reflecting the functioning of attention, decreased not only with aging but also with longer driving experience. Our results show that it is necessary to conduct further studies of psycho physiological markers of age-related decrease in short term memory depending on the activities at work in order to prevent accelerated aging and achieve professional longevity. PMID- 26856099 TI - [CACHEXIA AS A COMPLEX METABOLIC SYNDROME AND OTHER CAUSES OF WEIGHT LOSS IN ELDERLY]. AB - With a growing number of the elderly population, it is important to remember about the potential pathologic conditions, one of the main features of which is the weight loss (cachexia, anorexia, sarcopenia, hypermetabolism/hypercatabolism syndrome and etc.). These processes are interrelated and interdependent, especially in old age, and even modern medical literature does not clearly indicate the boundaries between this syndromes and pathological conditions. For instance, cachexia is a complex metabolic syndrome, resulting in the loss of muscle, but not always fat mass, arises in connection with the development of severe chronic systemic inflammation, which is especially inherent in the elderly, often accompanied by anorexia, and may also be part of another "old age syndrome"--sarcopenia. Sarcopenia is an age-related atrophic degenerative change in skeletal muscle, which occurs as a result of a long process with a very complex mechanism and is characterized by progressive and generalized decrease in muscle mass, its strength and by a risk of developing complications such as disturbance of mobility. Meanwhile, the earlier a physician suspects the onset of cachexia syndrome and/or other conditions involving abnormal weight loss, the more effective are going to be attempts to correct them with possible agents, which help to improve the prognosis and prolong life of the patient. PMID- 26856100 TI - [AGING, HEALTH AND ACTIVE LONGEVITY: SEMANTIC CONTEXT OF THEIR MENTIONING IN SOCIAL NETWORKS]. AB - Traditional media play a large role in shaping the image of oldsters as weak and sick members of society, while the gerontologists say the health of the elderly is quite specific. In a study of the views of the Internet audience, we tried to find out what this IT-competent part of society thinks on aging, what meanings they associate with aging and active longevity. PMID- 26856101 TI - [TECHNOLOGY OF SOCIAL WORK WITH ELDERLY MIGRANTS: INTERNATIONAL EXPERIENCE AND KAZAKHSTAN PRACTICE]. AB - The article explores the social problems faced by elderly migrants, in particular the elderly immigrants (oralmans), presents the experience of the EU countries for the social support to them, shows aspects of social work with elderly migrants and gives some recommendations on social protection of elderly migrants in Kazakhstan. PMID- 26856102 TI - [DIAGNOSIS COGNITION IN ELDERLY]. AB - This article provides recommendations for the diagnosis of cognitive in the elderly. An algorithm for the diagnosis of cognitive impairment, including four stages (clinical psychopathological, express psycho-diagnostic, clinical psycho diagnostic, instrumental), which can be used to identify elderly patients with preclinical forms of cognitive impairment and implementation of primary and secondary prevention efforts is presented; determination of the degree of cognitive impairment (mild, moderate, severe) in the elderly can recommend the future directions of medical and rehabilitation care. Recommendations can be used to provide guidance to general practitioners. PMID- 26856103 TI - [AGE-SPECIFIC METABOLIC THERAPY FOR ALCOHOL DEPENDENCE IN ELDERLY PATIENTS WITH REGARD TO THEIR AKMEOLOGICAL FEATURES]. AB - Aocoholism in the elderly determines tne protracted nature or tne pathological craving for etnanol in post-abstinence syndrome period, restricts arsenal of active pharmacotherapy and updates the search for new pharmacological therapeutic strategies. The results showed that the inclusion of the drug "Remaxol" in the treatment of clinical manifestations of craving for ethanol in post-abstinence syndrome period of associated forms of alcoholism in the elderly provides better in relation to conventional therapy dynamics of reduction of somatovegetative and neurological manifestations of alcohol withdrawal syndrome, as well as the main components of craving for alcohol, will increase the efficiency of outpatient treatment at the stage of remission. The duration of remission of mental and behavioral disorders caused by alcohol use in elderly patients is, apart from pharmacotherapy, due to such social and psychological factors and akmeological features as education, leadership potential, high social activity, a high level of social intelligence and its implementation, lack of intense intrapersonal conflict, high ductility and activity. PMID- 26856104 TI - [TREATMENT STRATEGY FOR PATIENTS OF OLDER AGE GROUPS IN VIEW OF AGE POLYMORBIDITY]. AB - The probability of side effects and complications of drug therapy of patients of older age increases several times. Therefore, during the working out the standards of care for diseases associated with old age, the geriatric expertise of medicine is important. Russian Association of Gerontology and Geriatrics developed a methodology determining the prognostic impact of the aggregate of drugs and other medical factors to the body of an old person. An expert committee to prepare a draft of geriatric standards was set up. PMID- 26856105 TI - [STRESS-INDUCED DEPRESSION IN OLD AGE: CLINICAL CHARACTERISTICS, PECULIARITIES OF THE PSYCHOGENIC SITUATIONS AND OF RELATIONSHIPS SYSTEM]. AB - In the context of increasing life duration the issue of prevention and treatment approaches to the basic forms of pathology, in particular--neuropsychic, becomes more important. One of these forms widely spread is depression, which is often triggered by stressful situations. The aim of this work was to study the features of stress-induced depression in old age group and to carry out the content analysis of such situations and specific system of relations in this group of patients. A study of 120 patients correctly divided into experimental and control groups with consequent comparative analysis revealed the predominance of depression anxiety component represented in even greater extent than in the general characteristic of the elderly depression, the high significance of stressful factors affecting the nearest environment of patients and the appropriate role of dominance of microsocial components in their system of relations. PMID- 26856106 TI - [PREVALENCE OF NON-CARIOUS CERVICAL LESIONS AND ABFRACTIONS OF DENTAL HARD TISSUES IN AN ADULT IN DIFFERENT AGES]. AB - The article is devoted to gerontostomatological and gender-specific prevalence of non-carious lesions of the hard tissue of teeth in adults. The paper presents data of epidemiological study on prevalence of non-carious lesions of dental hard tissues (high abrasion, erosion, wedge-shaped defects, hyperesthesia). Allocated to four age groups: young adults surveyed--from 22 to 39 years; middle ages--from 40 to 59 years; older--from 60 to 74 years of age; senile age--from 75 to 87 years. To determine the frequency of occurrence of different forms of non-carious lesions of the hard tissue of teeth we have used the following: general scientific and special methods: poll, dental examination, groupings, statistical and mathematical methods of processing sample. We have ranked low incidence of non-carious lesions of the hard tissue of the teeth in the sample surveyed: high abrasion, erosion, wedge-shaped defects of solid tissues, hyperesthesia. The features of clinical course of non-carious lesions have been determined. In particular a rare combined lesion of the teeth with advanced erasibility, wedge defects and erosion has been noted. Significant combination of the pathological processes of the hard tissue of teeth with their hyperesthesia has been found. Features of different forms of non-carious lesions of the hard tissue of teeth in different age periods of life have been determined. Noted that older people, due to non-carious esions of the hard tissue of teeth were more likely to require medical intervention aimed at addressing the ncreased sensitivity and loss of hard tissue of teeth by dental therapeutic activities or dental prosthetics. PMID- 26856107 TI - [Pregnancy wish and folic acid supplements]. AB - Folic acid is best known as the vitamin used to prevent neural tube defects during fetal development. Women who are planning a pregnancy best start with a daily intake of 0,4 mg of folic acid until at least 12 weeks after conception. Women at increased risk of having a child with a neural tube defect are recommended a daily dose of 4 mg until after the first 3 months of pregnancy. Pharmacists are well placed to inform women of childbearing age in person. Risk groups such as adolescents, low-skilled women or women of foreign origin need extra attention. PMID- 26856108 TI - [Stability of high-dose etoposide dilutions for use in hematopoietic stem cell transplantation conditioning regimens]. AB - High-dose etoposide is used in conditioning regimens for allogeneic stem cell transplantation. The limited stability of the drug induces barriers for its use for pharmacists, nurses and patients. When using a concentration of 10 mg/mL etoposide in physiologic saline, limitations can be overcome. This study provides stability data for etoposide in a high concentration that can be used in conditioning regimens. The solution was stable for 48h at 5 degrees C, for 48h at 5 degrees C followed by 8h at 25 degrees C and for 24 h at 25 degrees C. PMID- 26856109 TI - [The medication history: a tool to optimize the preoperative anesthesia consultation?]. AB - Since 2011, medication histories (MH) are performed at patient's admission in orthopaedic and visceral surgery wards, 40% patients have their surgery planned. During the anaesthesia's consultation, the anaesthetist reported usual treatments on a consultation report (CRI) which is also the preoperative prescription. The objective of this study was to evaluate if MH done prior to anaesthesia's consultation improve treatments report on the CR. A comparative prospective study was conducted over 3 months, including all patients for planned surgery. In the intervention group (I/G), a first MH was performed before the anaesthesia's consultation. When MH was not completed before the anaesthesia's consultation, patients were included in the control group (CG). For every patient, a MH was carried out at admission. Discrepancies between MH at patient's admission and CR, the clinical impact of these discrepancies and the sources used to write the MH were evaluated. 91 patients were included. Discrepancies were found in 56% of the JG and 42% in the CG (p=0.56). Main discrepancies were: missing drug on CR (25% vs. 22%; p=0.71). missing dose (21% vs. 25%; p=0.13) and missing dosage (8% vs. 18%; p=0.06). In the JG, discrepancies with potential significant severity were reduced by half (7% vs. 15%; p=0.26). 2+/-0.9 sources (average) were consulted to write the MH in the IG and 2.8+/-0.9 in the CG [p<0.05l. The MH availability before the anaesthesia's consultation does not seem to reduce discrepancies in the CR. This may be explained by the way the MH was elaborated in the CG, using the CR used as source in 75%. However, MH provides more reliable inforrr:tation on treatments for the anaesthetist than previously with a reduction of discrepancies with potential significant severity. However, the medication conciliation at admission process should be re-engineered and CR not considered anymore as a relevant source. In any case, MH has to be updated at patient's admission in order to take account of any undercurrent treatment's modification. PMID- 26856110 TI - [In Process Citation]. PMID- 26856111 TI - [In Process Citation]. PMID- 26856112 TI - Lymph Node Metastasis Status in Breast Carcinoma Can Be Predicted via Image Analysis of Tumor Histology. AB - OBJECTIVE: To develop a method whereby axillary lymph node (ALN) metastasis can be predicted without ALN dissection, via computational image analysis of routinely acquired tumor histology. STUDY DESIGN: We employed digital image processing to stratify patients based on the histological attributes of the primary tumor. We extracted image features that capture the nuclear and architectural properties of the specimen. We then used a novel machine learning algorithm to transform image features into a scalar score that provided not only a metastasis prediction but also the certainty of classification. RESULTS: We applied this procedure to 101 patients with a ground truth established by histological examination of the lymph nodes and found that 68.3% of the cohort could be classified, exhibiting a correct prediction rate of 88.4%. CONCLUSION: These results demonstrate a technique that potentially can be used to supplant existing surgical methods to determine ALN metastasis status, thereby reducing patient morbidity associated with over-treatment. PMID- 26856113 TI - Trophoblast Cell Proliferation and Apoptosis in Placental Development During Early Gestation Period in Rats. AB - OBJECTIVE: To show apoptotic and mitotic activities in differentiation and proliferation of the trophoblast through the techniques of immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate biotin nick end labeling (TUNEL), apart from achieving a morphological examination of placental development during early gestation in rats. STUDY DESIGN: Animals were sacrificed on days 7, 9, 11, and 13 of pregnancy. The samples removed from those rats were processed for purposes of microscopic analysis. The decidual structure resulting from the differentiation of the endometrial stromal cells in the uterus on days 7, 9, and 11 of pregnancy was determined. RESULTS: It was observed that the placenta, with an increasing trophoblast proliferation and differentiation, matures on day 13 of pregnancy, after which time the growth seems to be continuous. Density of PCNA-positive cells and PCNA immunostaining was observed to decrease in parallel with the age of pregnancy. The excessive number of apoptotic cells seen in the early periods of pregnancy decreased as the placenta matured. CONCLUSION: We speculate that the rat placenta grows to maturity by day 13 of pregnancy along with increased proliferation and apoptosis in the early days of pregnancy. In addition, a significant decrease of proliferation and apoptosis was observed in the placenta with increasing age of the pregnancy. PMID- 26856114 TI - Serum Osteopontin Levels Correlate with Clinical and Pathological Features in Non Small Cell Lung Cancer. AB - OBJECTIVE: A metaanalysis was performed to investigate the association between serum osteopontin (OPN) levels and the clinical pathological features in non small cell lung cancer (NSCLC) patients. STUDY DESIGN: A systematic literature search was performed to identify relevant studies published prior to September 2014 using PubMed and China National Knowledge Infrastructure databases. Data extracted from the selected studies were analyzed using statistical software. RESULTS: Based on our stringent selection criteria only 10 studies contained a combined total of 1,135 NSCLC patients. Our metaanalysis results clearly showed a strong correlation between serum OPN levels and multiple tumor parameters, such as TNM stage, histologic grade, and lymph node metastasis in NSCLC (TNM stage: RR = 0.69, 95% CI 0.62-0.77, p < 0.001; histologic grade: RR = 1.24, 95% CI 1.04 1.48, p = 0.016; lymph node metastasis: RR = 1.69, 95% CI 1.48 - 1.93, p < 0.001). CONCLUSION: Our findings revealed that serum OPN levels strongly correlate with clinical and pathological features in NSCLC patients. PMID- 26856116 TI - Effects of Potentilla fulgens as a Prophylactic Agent for Ischemia/Reperfusion Injury in the Rat Ovary. AB - OBJECTIVE: To investigate the effects of Potentilla fulgens as a prophylactic agent on ischemia/reperfusion (I/R) injury in the rat ovary. STUDY DESIGN: A total of 32 Wistar rats were divided into 4 equal groups: (I) sham, (II) ischemia, (III) ischemia + reperfusion, and (IV) IR + Potentilla fulgens. In groups I and II, ovary torsion was not performed and no drug was administered. In group III, 1 hour of ischemia and 2 hours of reperfusion were performed and no drug was given. Group IV received 400 mg/kg/day Potentilla fulgens intraperitoneally 5 days before I/R injury. RESULTS: The detorsion group showed preantral ovarian follicles and corpus luteum around the blood vessels and positive expression of vascular endothelial growth factor (VEGF). In the Potentilla fulgens group (IV) the stromal vascular endothelium with weak expression of VEGF was detected in small areas, and the ovarian follicles and the corpus luteum showed negative expression of VEGF. In the detorsion group the theca cells and apoptotic cells in preantral follicles showed positive expression of E-cadherin in the ovarian surface epithelium. Moreover, the E-cadherin expression was found to be positive in terms of follicular development, theca cells, granulosa cells, and corpus luteum. Potentilla fulgens, given after ischemic injury and apoptosis, was seen to decrease the effect of Bcl-2 expression. CONCLUSION: These results provide compelling evidence that the expression of E-cadherin in the ovary is an important component of ovarian function. PMID- 26856115 TI - High Proportion of Nuclear Phenotype Identifies Aggressive Cutaneous Squamous Cell Carcinoma. AB - OBJECTIVE: To develop a quantitative histopathology algorithm to predict which patients with cutaneous squamous cell carcinoma (cSCC) were likely to experience recurrence or metastases. STUDY DESIGN: This retrospective study of cSCC lesions compared patients with aggressive disease (n = 40) and those with nonaggressive disease (n = 35). Based on a previous study using nuclear karyometry, we determined that aggressive lesions had a high proportion of a specific nuclear phenotype. The proportion of those nuclei was used to derive an aggressiveness score for each lesion. The mean age of patients was similar in both groups, as were the locations of index lesions. RESULTS: The mean aggressiveness scorefor cases with aggressive lesions was 0.60 +/- 0.21 and was 0.28 +/- 0.35 for those with nonaggressive lesions. The overall accuracy in properly characterizing lesions was 72%. The area under the receiver operating characteristic curve was 0.80 +/- 0.05. In general, the aggressive nuclear phenotype is represented by elevated levels of chromatin clumps and short linear segments of dark chromatin/intense pixels. CONCLUSION: These data suggest that discriminant functions may be utilized to distinguish between aggressive and nonaggressive lesions at the time of diagnosis. PMID- 26856117 TI - Effects of Nicotine on the Submandibular Gland in Rats. AB - OBJECTIVE: To evaluate the histopathologic and immunohistochemical effects of systemic use of nicotine on the submandibular glands. STUDY DESIGN: We investigated the effects of nicotine on apoptosis and angiogenesis. Twenty adult Sprague-Dawley rats were divided into 2 groups: nicotine (n = 10) and controls (n = 10). The rats of the nicotine group were administered 2 mg/kg nicotine sulphate for 28 days. All animals were sacrified at the end of the study, and submandibular samples were removed and prepared for histologic examination. Proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and Bcl-2 antibodies were used for immunohistochemical examination. RESULTS: In the group treated with nicotine, we observed degeneration in serous cells and striated duct cells, dilation and hemorrhage of blood vessels in the stromal area, and an increase of fibrous tissue and edema. An increase was observed in the number of PCNA-positive cells as compared to in the controls. VEGF expression was found to be positive in vascular endothelial cells and inflammatory cells around the excretory ducts in the stromal area. The duct cells are immunoreactive to Bcl-2 antibody. Apoptosis was observed in some cells of the serous glands and ducts. CONCLUSION: Nicotine administration in this study induced apoptosis with salivary gland cell proliferation and is thought to have affected angiogenesis. PMID- 26856118 TI - Arteriovenous Malformation Masquerading as a Bladder Tumor. A Case Report. AB - BACKGROUND: Arteriovenous malformation (AVM) of the urinary bladder is an extremely rare benign vascular lesion. The clinical significance of bladder AVM lies in its presentation with painless hematuria and a hyperemic sessile bladder wall mass. CASE REPORT: A 47-year-old man presented with irritative symptoms and hematuria. Cystoscopically the lesion appeared as an erythematous, broad-based mass obscuring the right ureteral orifice. The patient underwent cystoprostatectomy for suspected mass lesion. Histologically the bladder tumor was composed of numerous malformed blood vessels of various calibers with myxoid degeneration. Immunohistochemically the bland endothelial cells lining in the vessels were reactive for markers of CD31 and CD34. Ki67 index was < 1%. The patient was free of disease 24 months after surgery. CONCLUSION: Our findings broaden the morphologic spectrum of bladder arteriovenous malformation and emphasize its deceptive presentation. PMID- 26856120 TI - Undertones. PMID- 26856119 TI - Tumor-like Accumulation of Uromodulin (Tamm-Horsfall Glycoprotein) in the Ureter. A Case Report of a Possible Diagnostic Pitfall. AB - BACKGROUND: Uromodulin, also known as Tamm-Horsfall glycoprotein (THG), is the most abundantly produced protein appearing in normal urine. Under normal conditions it has several functions, the most important being the provision of a water-tight boundary to the end path of filtration and the prevention of urinary tract infections. Under certain conditions THG is accumulated in urinary tract organs and the deposition is most often clinically silent. CASE: We report a case of 78-year-old man with clinically evident hydronephrosis and stenosis of the right ureter. Clinically, a neoplasm was suspected. Histological examination of ureter tissue revealed abundant deposits of THG in the ureter wall without any inflammatory reaction. CONCLUSION: In cases with deposition of eosinophilic material in the urinary tract organs, accumulation of THG should be considered in the differential diagnosis. To our knowledge this is the first report of tumor like accumulation of THG in the ureter. PMID- 26856121 TI - Validity, Reliability, and Insights from Applying the McGill Quality of Life Questionnaire to People Living with Parkinson's Disease (MQoL-PD). AB - Existing quality-of-life instruments for Parkinson's disease (PD) may not fully assess quality of life (QoL) for people with PD in a holistic and multidimensional manner. This study examines the subscale structure, validity, and internal-consistency reliability of the McGill Quality of Life (MQoL) Questionnaire in a sample of people with PD. This cross-sectional study evaluates the MQoL-PD by using Cronbach's alpha and principal components analysis. A total of 81 consenting people with PD from a tertiary care outpatient clinic were studied. Scores were tabulated for the motor Unified Parkinson's Disease Rating Scale (mUPDRS), the Short Form Health Survey (SF-36), the Parkinson's Disease Questionnaire (PDQ-39), the MQoL Single-Item Scale (MQoL-SIS), and the MQoL Questionnaire (MQoL). Cronbach's alpha for the MQoL-PD was: physical symptoms, 0.83; psychological symptoms, 0.59; and existential/support symptoms, 0.76. Important contributors to QoL in PD include mobility, bowel and bladder function, fatigue, and pain. The MQoL Questionnaire is a valid and reliable measure of physical, psychological, and existential/support symptoms for people with PD. PMID- 26856122 TI - Dysphagia in a Palliative Care Setting--A Coordinated Overview of Caregivers' Responses to Dietary Changes: The DysCORD qualitative study. AB - Primary caregivers (PCGs) are closely involved in preparing meals and feeding patients who are at the end of life, yet their responses to patients' swallowing difficulties have not been extensively analyzed. This study aimed to reach an understanding of PCGs' beliefs, values, and responses to dysphagia and dietary modifications in the palliative care setting. A total of 14 PCGs were interviewed and asked to share their thoughts and feelings about patients' dysphagia symptoms and the diet changes resulting from these symptoms. Qualitative descriptive analysis revealed four emerging themes: caregivers' knowledge, the symbolic role of food, emotional responses to dysphagia, and discordance with dietary recommendations. Our study found that PCGs appear to have a strong desire to continue feeding patients. The findings suggest that providing PCGs with knowledge and emotional support could help them to deal with this issue. PMID- 26856124 TI - An Interhospital, Interdisciplinary Needs Assessment of Palliative Care in a Community Critical Care Context. AB - AIM: There is a paucity of data on the provision of palliative care in the critical care settings of smaller community hospitals. This study aimed to identify the gaps that affect the provision of palliative care in a community critical care setting. SETTING: The study was set in a 10-bed, open intensive care unit and emergency department at a community hospital. METHODS: Mixed methods were used. Quantitative data included those drawn from databases and surveys; qualitative data included those collected from interviews, focus groups, and onsite walk-throughs and were analyzed with inductive coding techniques. RESULTS: Gaps were identified in palliative care, goals of care and end-of-life discussions, and resources. Community hospital healthcare professionals did not fully appreciate their essential contribution to the provision of palliative care in the intensive care unit. In addition, there was a lack of expertise, and a lack of interest in gaining expertise, in palliative/end-of-life care. CONCLUSION: Interrelated needs in a complex interprofessional, interhospital context were captured. Further studies are required to obtain data on palliative practice in the care of critically ill patients in various community hospital contexts. PMID- 26856125 TI - Indwelling Peritoneal Catheters for Managing Malignancy-Associated Ascites. AB - We investigated use of the tunnelled catheter in a large palliative population with malignancy-associated ascites employing retrospective analysis of a prospectively maintained patient database of tunnelled peritoneal catheter insertions for refractory malignancy-associated ascites or new rapidly accumulating ascites. We found that a 100 percent procedural success rate was achieved with 395 tunnelled catheters inserted in 386 patients. Catheters remained in situ for 66 days, on average. In a total of 22 cases (5.57 percent), complications developed. Nonfatal infections occurred most commonly--in 15 cases (3.80 percent). Ascites stopped reaccumulating in 16 cases (4.05 percent), leading to catheter removal. The mean Baseline Dyspnea Index was 3.79 (95 percent confidence interval [CI], 3.64-3.94); the mean Transitional Dyspnea Index postinsertion was 5.14 (95 percent CL, 4.94-5.34). In all, 13 patients completed serial European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires. Postinsertion, overall quality of life improved significantly (p < 0.05), as did all functional domains and fatigue, pain, dyspnea, and appetite symptoms. The tunnelled peritoneal catheter is feasible and safe and causes minimal complications. Its use results in significant improvement in dyspnea and improvement in overall quality of life for a small number of patients. PMID- 26856123 TI - Pain Symptoms Associated with Opioid Use among Vulnerable Persons with HIV: An exploratory study with implications for palliative care and opioid abuse prevention. AB - Current or former injection drug users with human immunodeficiency virus (HIV) are at high risk for pain, which adversely affects their quality of life and may increase their risk for illicit drug use or relapse. We explored associations between pain symptoms and substance use among injection-drug-using study participants with HIV who had histories of heroin use. Using generalized estimating equations and controlling for prior substance use, we found that pain in each six-month period was associated with the use of heroin and prescription opioids, but not the use of nonopioid drugs or alcohol. Routine clinical assessment and improved management of pain symptoms may be needed for persons with HIV and a history of injection drug use, particularly those with chronic pain, for whom there is increased risk for heroin use. PMID- 26856127 TI - Advance Care Planning Discussions in Chronic Obstructive Pulmonary Disease: A critical review. PMID- 26856126 TI - Assessment of Quality of Life of Family Members of Inpatients with End-Stage Disease. AB - BACKGROUND: An important aim of palliative care is to ensure the highest possible quality of life (QoL) for the family members of patients. AIM: We aimed to determine the QoL of family members of hospitalized patients with end-stage disease, as well as differences in QoL based on socio-demographic characteristics and the patient's functional status, psychological distress, and QoL. METHODS: Study participants were 292 family members of terminally ill patients at University Hospital, Ostrava, Czech Republic. To evaluate family members' QoL, we used the Quality of Life in Life-Threatening Illness--Family Carer Version (QOLLTI-F). We used the Hospital Anxiety and Depression Scale (HADS) and the Karnofsky Performance Status (KPS) Scale to assess patients' functional status and psychological distress. RESULTS: A statistically significant difference was found in QoL evaluation based on family members' socio-demographic characteristics in education, employment, and age. A significantly lower QoL score was observed for patients' life partners in six domains. A correlation was found between patients' poorer functional status and family members' lower QoL. We found lower global QoL in family members of patients with depression. CONCLUSION: Family support is a cornerstone of palliative care. Palliative care professionals should focus on at-risk family members--the life partners of patients, the unemployed, younger people, and those whose ill loved one has a poor functional status. PMID- 26856128 TI - Safe and Efficacious Use of Dexmedetomidine over a Prolonged Duration for Anxiolysis and as an Adjunct to Analgesia during End-of-Life Care. PMID- 26856129 TI - Unspoken Words. PMID- 26856130 TI - Moments That Last Forever. PMID- 26856131 TI - Sodium hypochlorite (dilute chlorine bleach) oral rinse in patient self-care. AB - Sodium hypochlorite (NaOCl), commonly known as "bleach," is widely accepted as being a safe and effective antiseptic against bacteria, fungi, and viruses. For over a century, bleach has been used to control or overcome infection in homes, hospitals, and even on battlefields, and in endodontics for disinfection of root canals. This paper reviews clinical studies on the efficacy of sodium hypochlorite oral rinse to combat dental plaque and gingival inflammation. Sodium hypochlorite is readily available as inexpensive household bleach, and we suggest that oral rinsing twice weekly with dilute bleach (0.25% sodium hypochlorite) constitutes a valuable adjunct to current methods of plaque removal. PMID- 26856132 TI - [CHEMICAL-ANALYTICAL ASPECTS OF THE COMPLEX IMPACT OF THE ENVIRONMENTAL FACTORS ON THE POPULATION'S HEALTH]. AB - In the study of the complex action of environmental factors the important step is the consideration of the multi-component composition of chemical substances which affect the human in the real conditions of the environmental pollution. In the study of complex action of environmental factors it is expedient to use the algorithm of chemical analytical studies, envisaging the implementation of the identity analysis with the quantitative assessment ofpossibly the fullest array of pollutants and the subsequent selection of leading indices on the base of the evaluation of the identified multi-component composition ofthe pollution according to the degree of their hygienic significance in view of the proposed set of criteria. PMID- 26856133 TI - [LIGHT POLLUTION AS THE HYGIENIC PROBLEM]. AB - Mass introduction of lighting devices according to the concept of "maximum coverage area" and multistoried buildings of cities gave rise to light pollution, which became a problem for astronomers, ecologists and hygienists. Analysis of modern lighting devices and installations has shown that about 30-45% of the luminous flux becomes the light pollution. Night lighting of cities causes both direct and indirect damage to the environment, leads to unnecessary energy wastes. So in the USA due to excessive light there is wasted about 2 million barrels of oil per day. Light pollution affects the human hormonal system, causing various health disorders, such as insomnia and depression as a consequence. The light pollution through the ganglion cells of the retina affects the synthesis of melatonin by the pineal gland (epiphysis) and contributes to its calcification, which greatly affects the human psyche. At present, many countries have been paying much state attention to this problem via delivery of national documents and change of the concept of the designing of lighting devices and installations. The essence of this concept--to shine with a preset quality of light only in the right place at the specified time interval. This reduces the light pollution, saves energy and increases the environmental safety of lighting. There is presented an example of a technical solution to reduce the light pollution in the application of the light panel in the form of the gradient of the light guide generator project development. PMID- 26856134 TI - [HYGIENIC ASSESSMENT OF INFORMATIZATION OF EDUCATION AND UP-BRINGING]. AB - During the last decade the quality of children's health declined, the level of children's aggression and aggressiveness increased. The consistent trend to increasing the quantity of children with the signs of motor disinhibition in different forms and manifestations was noted. In a study on the example of educational institutions of Irkutsk there was made an assessment of the impact of the intensification and informatization of education and up-bringing with the use of the index of the level of informatization. In preschool children over the information period mental performance was found to be characterized by an increase in the speed and decline in the quality of information processing, there are dominated increased aggressive background and unmotivated fears "out home", there are reduced values of endurance ratio of the cardiovascular system, higher levels of morbidity rate were noted. There was proposed a hygienic assessment of informatization of education and up-bringing with the use of the index of the level of informatization. PMID- 26856135 TI - [CONTENT OF POLYCYCLIC AROMATIC HYDROCARBONS IN SOILS OF ANTARCTIC STATIONS REGIONS]. AB - Comparative investigation of the soil contamination by polycyclic aromatic compounds (PAC) has been performed on examples of three polar stations of the Antarctic Peninsula. Data obtained are especially interesting for the Ukrainian Antarctic station "Academician Vernadsky" were no such investigations were performed since the technogenic spill of the hydrocarbons in 1992. Results of investigations permit to establish the values of the total background level of the PAC pollution as the base for the further monitoring of anthropogenic contamination. The data of analysis of soils from the all ecological zones of Point Thomas oasis (Polish Station "Genrik Artstovskiy") show the PAC homogenous background pollution to be similar to identified at the Galindez Island (the region of the station Academician Vernadskiy). Local pollutions are revealed in some areas of the Galindez Island. At the same time results of the investigation of the soils pollution from the various areas of the Fildes Peninsula (the station Bellingshausen.) show the absence of clearly pronounced contrast between the background and "hot points" that is likely related with the even pollution of the Peninsula. There was demonstrated the necessity of the development of regional standards and the establishment of a local background concentrations of PACs within the Antarctic Peninsula. At the same time, significant differences between the contamination of soils taken from the stations"Academician Vernadsky" and "Bellingshausen", apparently are associated with a lesser capacity of soils on the island Galindez that in the commensurable pollution creates greater concentrations in an investigated sample of the soil. There was shown the necessity of the development of the regional standard and the establishment of a local background concentrations of PACs within the Antarctic Peninsula. PMID- 26856136 TI - [PROBLEMS OF POLLUTION OF FISH PRODUCTION BY POLYCYCLIC AROMATIC HYDROCARBONS]. AB - There are considered the possibilities of the identification of sources of contamination of food products (from the external environment and due to cooking techniques of fish products) by polycyclic aromatic hydrocarbons (PAHs). There was revealed a relatively low informativeness for the identification of sources of PA H infoods products on the basis of the indicating ratios. There was shown the necessity of the adjustment of existing chemical markers. There was substantiated the possibility of the development of the indicating ratios as markers of carcinogenic and mutagenic activity of the PAH in terms of metabolic processes. PMID- 26856137 TI - [PRIORITY TECHNOLOGIES OF THE MEDICAL WASTE DISPOSAL SYSTEM]. AB - The annual production of waste in health care institutions (HCI) tends to increase because of the growth of health care provision for population. Among the many criteria for selecting the optimal treatment technologies HCI is important to provide epidemiological and chemical safety of the final products. Environmentally friendly method of thermal disinfection of medical waste may be sterilizators of medical wastes intended for hospitals, medical centers, laboratories and other health care facilities that have small and medium volume of processing of all types of waste Class B and C. The most optimal method of centralized disposal of medical waste is a thermal processing method of the collected material. PMID- 26856138 TI - [WASTE WATERS AS THE RESERVOIR OF INTESTINAL ENTERIC VIRAL INFECTIONS]. AB - In the paper there are presented data of field observations of the spectrum of viruses, contained in the waste waters. The studies were performed on the territory of the city and the territory unfavorable for hepatitis A. In the territory of the big city by RT-PCR in the waste liquid the enterovirus RNA was detected in 45% of samples; astroviruses--90%; noroviruses--80% and 15% of rotaviruses. Samples from 2 wells were slightly positive for the presence of HCV RNA A. In the waste liquid on the territory, unfavorable for viral hepatitis A, in 100% of the samples there were determined noro- and astroviruses RNA and adenovirus DNA, in 75%--enterovirus RNA; 50%--HAV RNA and a 25%--rotavirus RNA. PMID- 26856139 TI - [STUDY OF THE IMPACT OF CERTAIN ENVIRONMENTAL FACTORS ON THE VIABILITY OF THE SALMONELLA BACTERIA IN WATER FOR THE DETECTION OF ITS EPIDEMIC POTENTIAL]. AB - Salmonella from the tail water of the Don river was shown to be detected in 31.4% of samples with an average index of 23.5. Under experimental conditions, revealed long-term survival of Salmonella in the water exceeded in most of the experiments terms of preservation of E. coli and E. faecalis. The calculated high level of microbial risk of emergence of intestinal infections suggests the possibility ofwater route ofsalmonellosis. PMID- 26856140 TI - [SCIENTIFIC EVIDENCE FOR HYGIENIC STANDARDS HARMONIZED WITH INTERNATIONAL RECOMMENDATIONS FOR PRIORITY POLLUITIONS OF SOILS]. AB - In accordance with international approaches the ranking of permissible levels of chemicals in the soil for the Russian Federation was performed with the use of actual maximum permissible concentration (MPC), there were scientifically substantiated 33 standardsfor 26 substances and their combinations in the soil, differentiatedfor 6 groups offunctional areas for soil use. There is presented the algorithm determining the procedure for the establishment of MPC for unstudied chemicals for various functional areas of soil of populated areas, as well as draft of amendments to existing sanitary-hygienic regulations prior to processing the latter in accordance with modern requirements. PMID- 26856141 TI - [INDICES OF THE OXIDATIVE STATUS IN CHRONIC ADMINISTRATION OF COLLOID CARBONATE CALCIUM PRAPARATION WITH FAUCET AND LOW-MINERALIZED DRINKING WATER IN RATS]. AB - There are discussed the changes of an array of indices of the oxidative status in chronic administration of colloidal calcium carbonate preparation with faucet and low-mineralized drinking water to rats. Slight differences between significant effects of administration of 3 and 30 mg/L of preparation permit to suggest that the process of its incoming delivery into organism of rats has a bottleneck in the nature of total capacity of macrophages of intestinal lymphoid tissue to absorption of particles. PMID- 26856142 TI - [OPERATIONAL EXPERIENCE FOR THE PROGRAM FOR THE FORMATION OF HEALTHY LIFESTYLE SKILLS AMONG SCHOOLCHILDREN]. AB - In the paper there are presented data concerning the experience of the implementation of educational programs for schoolchildren "Being healthy is fashionable ". The program has been tested in the territory of the Penza Region. The awareness of students about the factors affecting health was shown to increase by 15,8% over three years of the realization of the program. The number of students taking systematic participation in sports competitions has increased by 3.8%, going in for various sports and physical exercises in sports sections and circles has increased by 2.6%. The prevalence of regular smoking among schoolchildren decreased by 4.1%. PMID- 26856143 TI - [SCHOOL AS A TERRITORIAL CENTER FOR HEALTH PROTECTION IN THE FAR NORTH]. AB - The problem of preservation of the health in children and adolescents in the process of education is extremely acute and continues to become more actual, especially in the regions of Far North and equivalent to them areas. In order to implement the effective health-protecting activity in the Komi Republic a complex model for the school activity as Regional Centre of health protection was developed and tested in four pilot areas. Within four years of the implementation there were performed studies on the assessment of the effectiveness of the work of schools in conditions of the model. In the article there are presented some results of the performed investigations. PMID- 26856144 TI - [HYGIENIC REGULATION OF THE USE OF ELECTRONIC EDUCATIONAL RESOURCES IN THE MODERN SCHOOL]. AB - We studied the effect of academic studies with the use a notebook computer and interactive whiteboard on the functional state of an organism of schoolchildren. Using a complex of hygienic and physiological methods of the study we established that regulation of the computer activity of students must take into account not only duration but its intensity either. Design features of a notebook computer were shown both to impede keeping the optimal working posture in primary school children and increase the risk offormation of disorders of vision and musculoskeletal system. There were established the activating influence of the interactive whiteboard on performance activities and favorable dynamics of indices of the functional state of the organism of students under keeping optimal density of the academic study and the duration of its use. There are determined safety regulations of the work of schoolchildren with electronic resources in the educational process. PMID- 26856145 TI - [CLINICAL AND BIOCHEMICAL CHARACTERISTICS OF DISORDERS OF THE NERVOUS SYSTEM AND THE RISKS OF COMMON PATHOLOGICAL SYNDROMES IN MERCURY PRODUCTION WORKERS]. AB - The occupational factors are assigned one out of main parts to the development of occupational and comorbid pathology. At the same time the social aspects of labor relations act as the most important factors influencing on the workers' self assessment of health status. Quantitative risk assessment of the common pathological syndromes has identified the excess of share of persons with a minimum level of risk over the medium and high. In the structure of risks of common pathological syndromes there are prevailed risks for disorders of the cardiovascular and nervous systems and borderline mental disorders, which is a response to the impact of not only industrial, but also psychosocial factors. The results of self-assessment of health status and clinical examination of employees in conditions of mercury exposure show the similarity of the structure of diseases in these cases. In either event there are dominated diseases of the nervous and mental sphere, and from the comorbid pathology disorders of the cardiovascular system are prove to be important. Clinical manifestations of the mercury exposure, ranging from pre-clinical manifestations to marked changes from the side of the nervous system in toxic encephalopathy, are characterized by the presence of hyperkinetic syndrome. For pre-clinical and early forms of mercury poisoning there is also typical the presence of asthenic (emotional lability) disorders with autonomic dysfunction. Comorbidities in an internship working was manifested primarily by diseases of visual organs, cardiovascular system and diseases of the musculoskeletal system. Observed disorders of the nervous system and psycho-emotional sphere are caused, inter alia disturbances of the balance of catecholamines (the rise of norepinephrine in dynamics with a concomitant increase in the coefficient reflecting the degree of its metabolism: norepinephrine/epinephrine and norepinephrine/(adrenaline + Normetanephrine)) in the body. PMID- 26856146 TI - [HYGIENIC ASSESSMENT OFWORKING ENVIRONMENT FOR REPAIRERS OF RAILWAY ROLLING STOCK IN PLANT CONDITIONS]. AB - The comprehensive hygienic assessment of working environment for main occupational groups Railway Car Repair Plant in factory conditions shows that workers are exposed to the impact of factors of chemical nature in concentrations exceeding maximum allowable (lead, manganese, alkali caustic, sulphuric and nitric acids, chromium trioxide, silicon-containing dust, white corundum, diiron trioxide, silicate-organic dust, wood and carbon dusts), the high level of noise, the local vibration, insufficient levels of artificial lighting. The manual work is used, that determines the high severity of the labor process in the most of workers. There was identified the inconsistency of quality and quantitative estimation of the work conditions on chemical factor at implementation of various types of control: certification of workplaces on work conditions, productions and state control. There was given an a priori evaluation of the occupational risk in the three main workshops, there were detected 13 occupations with mild (moderate) risk, 9 occupations with average (significant) risk, 6 professions with high (intolerable) risk category and 1 occupation--with very high (intolerable) risk category. Low indices of occupational diseases according to official statistics were establishedfail to be consistent with a high probability of their occurrence in the production. PMID- 26856147 TI - [THE EFFECTIVENESS OF EDUCATIONAL PROGRAMS FOR THE IMPROVEMENT OF POPULATION DIETARY PATTERNS AND PREVENTION OF ANEMIAS]. AB - There was performed an experimental study of the use of educational programs as tools of the improvement of the structure of nutrition and primary prevention of anemias associated with nutrition. Educational programs were differentiated for each of the target audience (pupils of 5-7 classes, 1-4 year students of the medical school, the adult unorganized population; n = 645). Their efficacy was evaluated with the use of issues included in the educational program and analysis of the actual nutrition (only in groups of students and adults). Performance assessment were: testing on the issues included in the educational program and analysis of actual of dietary intake (only in groups of students and adults). Testing was performed at the points: before the intervention, immediately after 6 and 12 months after intervention. An analysis of the frequency of food consumption with an estimation of the actual consumption of nutrients was carried out at the initial and final points. There was noted the low level of public knowledge about the principles ofrational nutrition: the proportion ofcorrect answers, reflecting the level of awareness ofconstructing an optimal diet in the starting point of the study was 25%for schoolchildren, 45%--in adults, 35%--the students, after the intervention--75%, 90% and 85% respectively. One year after the implementation of the educational program the level ofresidual knowledge of study participants remained at a level above the original (the proportion of correct answers during testing of schoolchildren--50% (p < 0.001 to baseline), in adults--60% (p = 0.0005), students--60% (p < 0.001). There were also noted positive changes in the structure of nutrition of study participants 12 months after the intervention: in relation to the initial level there was increased consumption of ascorbic acid and calcium in students, decreased consumption of animal fats in adults and students, there was noted a trend towards increased consumption of dietary iron (p = 0.059). The obtained results testify to the effectiveness of educational programs as a means for the improvement of the structure of the nutrition in different groups of the population and primary prevention of micronutrient deficiencies and diseases with dietary risk factors, including anemia. PMID- 26856148 TI - [PREVENTION OF ALIMENTARY-DEPENDENT PATHOLOGY IN ADOLESCENTS ON THE BASIS OF HEALTH RELATED QUALITY OF LIFE]. AB - With the aim of the substantiation of hygienic measures for the improvement of the prevention of nutrition-related diseases among adolescents there was performed an analysis of indices of the health-related quality of life, lifestyle features, the character of nutrition and health of adolescents aged of 13-17 years in the territory of the Omsk region (n = 427). The study of the health related quality of life was performed with the use of the validated Russian language version ofthe general questionnaire PedsQL-4.0. According to the results of the study there were identified the priority factors influencing the formation of the quality of life of adolescents. The nutrition of adolescents has a significant influence on the formation of quality of life. Among the many parameters that characterize the nutrition, the greatest contribution to the quality of life is made by the factor of "the amount of consumed meat products". The decline in quality of life was noted in adolescents with chronic diseases or disorders of the nutritional status as overweight. There were marked forward looking possibilities of prevention of nutrition-related diseases on the base of indices of the quality of life, including measures for correction of adolescent nutrition, in-time detection of disturbances of the nutritional status, early diagnosis and treatment of chronic diseases. PMID- 26856149 TI - [APPLICATION OF BIOMONITORING METHODOLOGY FOR THE ASSESSMENT OF EXPOSURE TO ENVIRONMENTAL POLLUTANTS]. AB - In this article there are presented the current views on the technology for the assessment of the exposure to chemical pollutants with the use of the methodology of human biomonitoring and the main advantages of the latter are highlighted. There are presented main problems of the implementation of biomonitoring studies in Russia such as: beginning with the lack of the national system of the biomonitoring, and accomplishing with the inconsistency in the data within the country, the inability to assess the trend according to levels of exposure in the regional or national context. Due to the inconvenience of the Russian regulatory basis on human biomonitoring, there is persisted technological backwardness in terms of the delivery of the design, presentation and evaluation of research results, which results in the decline of the significance of biomonitoring for public health in the country. There is preserved a need for standardization and harmonization of methods and procedures of human biomonitoring (HBM) in Russia with international requirements. A serious concern is the lack of Russian programs on standardization of procedures and interlaboratcy comparison of results according to biomarkers of the exposure, the insufficient involvement of national laboratories in international programs of the comparison, the difficulties with the acquisition of standard samples of the compositionfor different environmental pollutants in biological tissues. The restraint ofthe development of HBM in the Russian Federation is caused by a complex of reasons. The most urgent task is the development of the national concept of the system with subsequent formation of technological, institutional and organizational framework of biomonitoring, as well as the improvement of Russian normative methodical base. PMID- 26856150 TI - [THE STUDY OF MANIFESTATIONS OF ENVIRONMENTAL HAZARDS AT THE REGIONAL LEVEL]. AB - Elaborated methodological approaches to the monitoring of the state of ecological safety are based on the use of systems analysis of conditions and consistent patterns of the formation of the ecological danger search for effective means and methods of safety management. Ecological hazard is considered as a hierarchical structure, consisting of types, classes, species and subsubspecies. In industrially developed regions the most significant are technogenic and sociogenic classes. The sociogenic class of danger was proved to be primary in its formation, as the level of environmental awareness is largely determined by the degree of impact on human health and environment, manifestations of the danger of other classes are depend on it. When analyzing the state of danger there was applied the anthropocentric approach. There was used an assembly of characteristics considering the health status of the population of the certain territory under the influence of factors of environmental hazard. On the base of the colligation of literature data and the results of own observations there was suggested a generalized index of the state of the population'S health in socio economic areas, there were selected zones with differing level of the technogenic loads and also rural areas beyond objects of technogenic impact. On results of studies there was proved the relationship between the level of the environmental hazard and state of the population's in various socio-economic zones. PMID- 26856151 TI - [THE USE OF OPEN REAL ESTATE DATABASES FOR THE ANALYSIS OF INFLUENCE OF CONCOMITANT FACTORS ON THE STATE OF THE URBAN POPULATION'S HEALTH]. AB - There was suggested a new method of the assessment of certain social-lifestyle factors in hygienic health examination of the urban population, based on the work with the open real estate databases on residential areas of the given city. On the example of the Moscow FlatInfo portal for a sample of 140 residents of the city of Moscow there was studied the distribution of such available for analysis factors as a typical design of the building, where studied citizen resides, the year of its construction and the market price of 1m2 of housing space in this house. The latter value is a quantitative integrated assessment of the social and lifestyle quality of housing, depending on the type and technical condition of the building, neighborhood environment, infrastructure of the region and many other factors, and may be a useful supplemental index in hygienic research. PMID- 26856152 TI - [METHODOLOGICAL APPROACHES TO THE CALCULATION OF ACTUAL AND PREVENTED AS A RESULT OF CONTROL AND SUPERVISORY ACTIVITIES, MEDICAL-DEMOGRAPHIC AND ECONOMIC LOSSES, ASSOCIATED WITH THE NEGATIVE IMPACT OF ENVIRONMENTAL FACTORS]. AB - In the article there are reported the methodological approaches to the calculation of actual and avoided as a result of control and supervisory activities of economic losses caused by mortality, morbidity and disability in the population, associated with the negative impact of environmental factors. There is suggested a consistent solution of the chain of problems: the establishment of cause-and-effect relationships between indices of the health status and indices of the quality of the environment; indices of the quality of the environment and indices of the control and supervision activity of organs and institutions of Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing calculation of the cases of violations of health prevented as a result of the activity ofthe service; evaluation of their economic equivalents. Approbation of approaches on the example of the Russian Federation allowed to establish that as a result of the activity of organs and institutions of Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing in 2013, a positive trend was observed on 51 indices of quality of the habitat environment, there were prevented about 160 thousands of deaths and more than 2 million cases of disease that would be held in conditions of the lack of adequate control and surveillance measures in the field of sanitary and epidemiological welfare of the population. Loss prevention of gross domestic product (GDP) amounted to more than 120 billion rubles, Tax shortfalls in the federal budget- about 25.7 billion rubles. With taking into account the costs of the federal budgetfor the activities of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing in 2013 in part to ensure sanitary epidemiological surveillance in the amount of 11.386 billion rubles there was prevented loss of GDP of 10.56 rubles per 1 rub. of the cost of the federal budget and there was warned the shortfall of taxes to the federal budget of 2.28 rubles per 1 rub. of the cost of the federal budget. PMID- 26856153 TI - [COMPARATIVE ANALYSIS OF TRACE ELEMENT COMPOSITION OF HAIR IN URBAN RESIDENTS OF WESTERN SIBERIA]. AB - There was performed a study of the element status (hair analysis) of the population of the two cities of Western Siberia: Surgut (n = 350) and Omsk (n = 385). Detection of elements was performed by atomic emission and mass spectrometry methods. The population of Surgut when compared with residents of Omsk bioelements were characterized by a more high content of B, Cu, Co, Fe, Mg, I, Zn (p < 0.001), and a lower content of Cr, Se (p < 0.001). Scarce elements for Omsk residents were 1, Se. In hair of Surgut residents in more higher concentrations there were detected toxic and potentially harmful elements such as Pb, Hg, Be, Cd, Li, Sn (p < 0.001). At the same time there were lower than in Omsk residents values of concentrations of Al, As, V In comparison groups there are established statistically significant differences of coefficients used for the evaluation of the metabolic activity, such as the Na/K, Ca/K, Na/Mg, Fe/Cu. In a sample of the city of Surgut coefficients Ca/K, Fe/Cu and "toxicity index" had the high values. The established differences in the availability of macro- and trace elements for the population of territories are determined by climatogeographic, geochemical features and the specificity of the structure of nutrition. PMID- 26856154 TI - [GENETIC EVALUATION OF CONTROL VARIANTS OF STRAINS SALMONELLA TYPHIMURIUM, USED IN THE TEST SALMONELLA/MICROSOME (Ames test)]. AB - There were analyzed data of controls with solvents (DMSO and distilled water) of experiments performed in the laboratory of genetic monitoring in 2004-2014 on Salmonella typhimurium TA 100, TA 98 and TA 97 strains in the versions without and in the presence of metabolic activation. For all strains there was no revealed effect of the either solvent or system of metabolic activation on the average number of colonies of revertants in control. Generalized parameters (historical control) of the average number of colonies of revertants per plate: TA 100--number of experi- ments--317, average--118; 95% intervals of 71-165; TA 98--number of experiments--389, mean--22; 95% intervals 9-36; TA 97--the number of experiments--217, average--142; 95% intervals of 94-191. PMID- 26856155 TI - [THE LEVELS OF SPECIFIC AUTOANTIBODIES AND RISKS FOR THE FORMATION OF PATHOLOGICAL PROCESSES IN CONDITIONS OF INHALATION EXPOSURE TO CHEMICALS]. AB - The exposure of atmospheric pollutants on the organism may be a precondition for the development of pathological processes in organs and system to which they have tropicity. The change in the levels of specific autoantibodies occur long before the clinical manifestation of the disease. The aim of the study was the investigation of relationships between the levels of specific autoantibodies and risks of the formation of pathological processes of organs and systems in conditions of the inhalation exposure to chemicals. There was made an assessment of levels of the air pollution and indoor air in the industrial centers of Eastern Siberia. There were calculated indices of danger from the inhalation exposure of chemical compounds and the risks for the development of the pathology of organs and systems. There was studied the relative content of specific autoantibodies to the organs and systems that are at high risk of the development ofpathological processes. The highest overall risks for the development of respiratory diseases, immune system and cardiovascular system were established in schoolchildren residing in areas of high and medium levels of air pollution. In general, the identified changes in the content of specific autoantibodies characterizing the state of the major organs and systems ofchildren residing in areas of high riskfor the development of pathological processes associated with the content of chemical compounds in the air cannot be properly interpreted as the realized risk of environmental impacts and require further study. PMID- 26856156 TI - [SYNERGISM OF PRECONCEPTIVE RADIATION EXPOSURE AND PARENTS' ONCO-PATHOLOGY IN THE RISE OF CARCINOGENIC RISK IN THE OFFSPRINGS OF PROFESSIONAL EMPLOYEES]. AB - The problem of carcinogenic risk in offsprings of individuals exposed to radiation is challenging and insufficiently studied. In that there are no evaluations of the interaction between radiation and non-radiation factors. The aim of the study was the analysis of interaction of preconceptive radiation exposure and parents' onco-pathology in cancer mortality in offsprings (F1) of workers (fathers) of the Mayak Production Association exposed to a wide range of doses of radiation over a year prior conception. The number of offspring is 8191 individuals (4180 men and 4011 women). The analysis was performed with the use of fourfold table and eightfold tables. The interaction offactors was estimated on the base of the additive and multiplicative models. The studied factors were independent. The odds ratio (OR) of cancer mortality in the offspring with parents' oncopathology (1.43) was insignificant. OR of cancer mortality in preconceptive radiation exposure in a dose over 110 mGy and without parents' onco pathology was 2.61 (1.52-4.49), and in their combination--3.86 (1.93-7.71). Index of synergism of preconceptive radiation exposure and parents' onco-patholog in the rise of carcinogenic risk in the offspring was 1.34 and the character of their interaction was multiplicative. Thus, for the first time there was established the interaction between radiation and non-radiation factors in the synergism sort in the increase of carcinogenic risk in the offspring of people exposed to radiation. PMID- 26856157 TI - [TRENDS IN HEALTH OF THE POPULATION IN THE AREA OF THE TENGIZ FIELD]. AB - At the present the Caspian oil and gas field became extremely important for the economy of Kazakhstan and it has entered a qualitatively new stage of its development. In connection with the intensive development of these fields the attention of both scientists and health practitioners is attracted by problems of populations' health. In the article there are presented data of a study of the quality of main objects of environment, health condition, demographic indices of and morbidity rate of the population of the Zhylyoi district of the Atyrau region. The population resides in the region of influence of the Tengiz oil and gas field. The level of mortality in Zhylyoi for the periodfrom 2006 to 2013 was establishe to decline, as birth rate rather increased. Indices of the population's structure retain the tendency to the progressive type, possibly in relation with urbanization and industrial migration of population, that increased in last years. The district mortality rates are below national, regional and urban values. Natural population growth in Zhylyoi has increased by 27.6%. The analysis of primary morbidity of the population of the Zhylyoi district in dynamics from 2006 to 2013 shows a some decrease. In the structure of the morbidity there was noted a decrease in the proportion of diseases of the skin and subcutaneous tissue, respiratory diseases, digestive organs. However, the proportion of blood diseases, diseases of the hematopoietic system and blood flow has increased. Alongside this in the region there is clearly discernible the scarcity of doctors, qualified nurses and beds. PMID- 26856158 TI - [REAL AND UNREAL BACKLASHES OF AEROSPACE ACTIVITY FOR THE HEALTH OF POPULATION RESIDING NEAR AREAS OF FALL OF BEING SEPARATED PARTS OF CARRIER ROCKETS]. AB - Since the late 1990s, the ongoing debate about the consequences of the rocket space activities for the health of people residing near areas offall ofseparatingfrom parts of rockets. Some scientists (Kolyado IB et al., 2001, 2013; Shoikhet YN et al., 2005, 2008; Skrebtsova NV 2005, 2006, Sidorov PI et al., 2007) argue that the main cause of morbidity is the effect of unsymmetrical dimethyl hydrazine (UDMH). However, environmentalists find it only in areas offalling fragments of separated parts of carrier rockets. Presented in the article data were obtained as a result of perennial epidemiological and hygienic research. There was performed a hygienic assessment of the content of chemical substances in water soil andfood, nutritional status and health risk near areas of the district of falling 310 and 326. There were studied conditions of work and the health of military personnel at the sites of storage of propellant components. The relationship between revealed diseases and UDMH was not established, but there was their causality due to the influence of environmental factors characteristic of territories and living conditions. In the settlements near the area of falling district 310 the share of extremely anxious persons was shown to be 1.8 times higher than in controls, which is caused by cases of falling fragments stages of carrier rockets in the territory of settlements. PMID- 26856159 TI - [RELATIONSHIP BETWEEN THE PREVALENCE OF CHRONIC NONINFECTIOUS DISEASES AND ELECTROPHYSICAL STATE OF THE ENVIRONMENT]. AB - In the paper there is evaluated the relationship of features of electronic state of the environment with a level of chronic, noninfectious diseases (CNID) in the regions of Russia, obtained on the basis of the monitoring measurements of the intensity of natural background electronic Bose condensate (BEBC) of natural ecosystems in a number of Russian regions and seas of the Arctic Ocean. The assessment of BEBC was implemented on results of measurements of redox state of distilled water being in the contact with natural water. The equilibrium redox state of distilled water, determined by the influx of electrons (quantum reduction) outside, is proportional to the intensity of BEBC. The obtained data attest to an increase in the intensity of the background of EBC in Siberia regions and, especially, within the limits ofwaters of Lake Baikal (the redox potential of the surface water in the lake ~ -70mV). Also there is observed a strong dependence of the background EBC in the latitudinal direction. Low levels of background EBC were noted in the Arkhangelsk region and the north-eastern Chukotka. Functioning of international systems of plasma sounding of ionosphere (such systems as HAARP) were established to have a detrimental effect on the background EBC in these regions. According to the results of measurements of the relative values of intensities of natural background of Bose condensate of electrons there was constructed the dependence reflecting the relationship of the prevalence of noninfectious diseases in the regions of Russia with the redox state of distilled water which can be characterized as a significant (regression coefficient R2 = 0.78). The relationship between noninfectious diseases (NID, %) with the intensity of the background of EBC (Ib rel. units) is estimated by the equation: NID [%] = 0.24Eh [mV]-25, where Eh ~ I/Ib. Numerical evaluations show that an increase in the biosphere redox potential of water by 90mV leads to an increase of the primary incidence by 20% (relatively to the average values for Russia). Analysis of results attests to the relationship of CNID with the electrophysical state of the environment that allows from different positions to arrive to true causes of their emergence, associated with changes in the electrophysical conditions of habitation and human activities that lead to the nascency of cellular metabolic disturbances. PMID- 26856160 TI - [STATE OF NONALLERGIC HYPERSENSITIVITY UNDER THE EXPOSURE TO ADVERSE ENVIRONMENTAL FACTORS]. AB - Now a number of allergopatologies is shown to be formed as non-allergic hypersensitivity. Research of this state is especially important when studying a question of formation of a condition of a chemical sensitization in response to the contact of a human body with chemical pollutants. For diagnostics of reactions of non-allergic hypersensitivity the test was developed for an assessment of activation of basophiles by specific allergens (the test of activation of basophiles by method of a flowing cytometry Flow Cast(r) (BD FACSCalibur)). It is possible to judge by activation on an expression of some receptors on a surface of these cages (CD63). Examination of a group of persons, having continuous contact with means of household chemicals was performed. In 54.5% of the examined persons the percent of CD63-of nonspecific activated cages was revealed to be at the level of 16-65% that gives the grounds to assume existence of a condition of not allergic hypersensitivity. Thus, the test of activation of basophiles by method of a flowing cytometry can be used for a differentiation of an IgE-dependent allergy from a condition of non-allergic hypersensitivity. PMID- 26856161 TI - [THE FEATURES OF PREVALENCE OF SKIN DISEASE AS AN INDEX OF ECOLOGICALLY RELATED MORBIDITY OF POPULATION IN BIOCLIMATIC ZONES OF PRIMORYE KRAI]. AB - There are presented results of the socio-hygienic analysis of ecologically related skin pathology ofthe population of Primorsky Krai. The aim of the work is to establish the patterns of distribution of ecologically related skin diseases in various ecological bioclimatic zones of Primorsky Krai. There was performed an analysis of skin diseases ofform 12 according to ICD-10 main demographic groups (children, adolescents and adults) of the population of Primorsky Krai, residing in various bioclimatic zones of Krai with different levels of environmental stringency in rural and urban areas for the period of 2000-2013. There were established causal-effect relationships of the prevalence of skin diseases, as ecologically related pathology. The level of the prevalence of skin diseases among the population in the Primorye region depends on bioclimatic zones, the degree of the stringency of the environmental situation and combinations of environmental factors. The prevalence of skin diseases in adults, adolescents and children, as the organism's response to the impact ofthe parameters ofthe environment is affected by the complex offactors, the main of them are hygienic: the sanitary--hygienic level of ambient air pollution, the specification of chemical pollution and adverse physical factors in urban and rural settlements, the characteristics of the state of the soil. The medical-sociological research of the lifestyle of the population was performed on the basis of a specially designed questionnaire. The questionnaire included three arrays of issues: environmental, hygienic and social. On the basis of medical and sociological research with the use of multivariate analysis, method of correlation pleiades advanced by P. V. Terentiev, lifestyle and psycho-emotional factors, socio hygienic, bioclimatic factors were found to play an important role in the prevalence of ecologically related pathology of skin in residents of Primorsky Krai. Differences in responses between urban and rural residents living in areas with various environmental stringency, confirm the preposition about the ambiguity of the approach to the solution of social, hygienic and environmental problems in areas with different socio-economic situation. The obtained results of the study allow us to determine the main directions of treatment and prevention and to develop targeted prevention programs. PMID- 26856162 TI - [CREATION OF THE UNIFIED SYSTEM OF ANTI-MICROBIAL AND MICROBIAL PROTECTION AS ACTUAL HYGIENIC PROBLEM]. AB - In the article there are substantiated the main directions of hygienic measures for the anti-epidemic protection of people. There are considered theoretical, methodological, material and organizational aspects of the development of a unified system of anti-microbial and microbial protection. The scientific basis for its effectiveness is shown to be a transcription of peculiarities of the susceptibility to various antimicrobial agents for different types of micropathogens in comparison with saprophytic and beneficial microflora. There is proposed to use in disinfectology a certain analog of the "chemotherapeutic index"--a relative index of the efficacy and safety of the introduction of the appropriate disinfectant into the environment. PMID- 26856163 TI - [THE REGULARITIES OF DEVELOPMENT OF CANCER MORBIDITY AND MORTALITY RATE OF THE POPULATION IN THE REPUBLIC OF TATARSTAN AND FINLAND]. AB - There were revealed gender differences in cancer morbidity and mortality rate in the Republic of Tatarstan over the period from 1996 till 2013. The morbidity rate was increased by 1.54 times in both urban and rural areas. The morbidity rate level in men was two times higher than in women. The maximum share of new cases of cancer morbidity according to the primary lesion in men in Finland in 2008 2012 was noted in the age groups of 60-64, 70-79 and 85 years and older. PMID- 26856164 TI - [CHEMICAL FACTOR IN THE DEVELOPMENT OF ENDOCRINE DISEASES]. AB - In the presented review there is discussed the dynamics of diseases of the endocrine system of the population, including diabetes and thyroid pathology and the modern view on the importance of chemical factors (pesticides, arsenic, essential and toxic elements) for their formation. PMID- 26856165 TI - [MODERN TRENDS IN THE MORTALITY OF THE POPULATION IN THE REPUBLIC OF TATARSTAN]. AB - The analysis of total mortality coefficients on the example of 43 regions of the Republic of Tatarstan (RT) showed the significant spread of values from 9.0 to 22.2 per hundred in 2006, and from 9.0 to 18.4 per hundred--in 2013. In the dynamics there were observed divergent processes of the formation of the total mortality of the population (the stable level in two districts, the decline--in 29 districts and the gain--in 12 districts). In the framework of 43 districts of the RT there were identified the one with the consistently low level, 12--with a stable average levels of total mortality, 18--with consistently high levels, 11- with the positive trend of the transition from high levels into middle ones and the one--with a negative trend of the transition from middle levels to high levels of the total mortality. The achievement of the indicator value is planned only in three districts in the group of 13 districts with the low and middle level, and a unfavorable prognosis--in 30 districts of RT PMID- 26856166 TI - [HYGIENIC ASSESSMENT OF WORKING CONDITIONS AND HEALTH OF EMPLOYEES OF THE "SIBERIAN LIFT CO., LTD."]. AB - There was carried out a hygienic assessment of the working conditions and health of employees of the "Siberian Lift Co., Ltd.". When studying occupational factors on workplaces intensity, the temperature radiation, natural and artificial lighting, and also the content of chemicals they were revealed to fail to answer to the hygienic specifications. It is established that in 82% of employees the class of working conditions was detected as admissible (2) and in 18%--harmful (3.1 and 3.2). Results of the performed periodic medical examination of employees of the "Siberian Lift Co., Ltd.". It is testified that 6.14% out of them are persistently unfit of the work with harmful and (or) dangerous substances and occupational factors also. 4.68% of employees demand an additional examination. 11,70% of workers need for out-patient examination and treatment. Sanatorium treatment is required for 1 (0.29%) the person. 4,68% of employees of the "Siberian Lift Co., Ltd." need dispensary supervision. There are suggested measures for the improvement of working conditions and health of the employees. PMID- 26856167 TI - [OCCUPATIONAL PREVALENCE OF MYCOBACTERIUM TUBERCULOSIS INFECTION AMONG HEALTHCARE WORKERS]. AB - Professional prevalence of tuberculosis of workers of health care is the important medico-social problem. MATERIALS AND METHODS: The study is based on the observation of the epidemic process of tuberculosis in the Omsk region for 2000 2014. Material for the study was the data of the forms of Federal statistical observation. There were used observational descriptive and evaluative research methods of the study. RESULTS: In the Omsk region on the background of the downtrend of tuberculosis incidence there were observed qualitative changes in the nature of bacterioexcretion, characterized by the widespread occurrence of multidrug-resistant Mycobacterium. Over the study period 154 cases of occupational diseases in workers of medical institutions were registered Tuberculosis accounted for 80.5% of cases; at that 77.4% are employees of phthisiatric institutions, out of them nursing staff--48.3%, medical attendants- 20.2%, doctors--18.5%, employees of the bacteriological laboratory--6.4%, workers of other support units--6.4%. Among diseased patients 41.1% were persons with the experience of working in harmful conditions from 1 to 5 years, 20%--experience of 5-10 years, 8.8%--working experience of 10 to 15 years, 29%--more than 15 years. In patients there was prevailed tuberculosis of respiratory organs--85.4% of cases, extrapulmonary forms of tuberculosis (tuberculosis of the genitourinary system, peripheral lymph nodes, eyes, central nervous system) accounted for 14.6%. About 30% of cases of tuberculosis among health care workers were accompanied by bacterioexcretion. CONCLUSIONS: In conditions of the wide spread of drug-resistant Mycobacterium tuberculosis it is necessary to optimize the approaches to the prevention of tuberculosis among health care workers. PMID- 26856168 TI - [HYGIENIC ASSESSMENT OF WORKING CONDITIONS OF EMPLOYEES OF BROADCASTING CENTER]. AB - Hygienic assessment of working conditions of employees of the Omsk Regional Broadcasting Centre was performed on data of the analysis of materials of certification of workplaces. There were examined materials concerning 65 core profile workplaces, where 130 persons, including 35 women work. There was determined health risk for personnel in dependence on working conditions. The staff was noted to be exposed to the adverse impact of the following factors: chemical, physical (noise, general and local vibration, non-ionizing radiation, microclimate, lighting), severity and intensity ofwork. Class working conditions for 13,5% of workplaces on noise, 35.4% on non-ionizing radiation was assessed as a harmful of the first degree. Lightness indices at 78.5% of the workplaces did not meet the requirements of sanitary norms. At 7.7% of the workplaces levels of hardness of labor were assessed as harmful. The impact of such factors as biological, infrasound, ultrasound, ionizing radiation, aerosols with mainly fibrogenic action, was absent, their assessment was not carried out. Working conditions at 83.1% of workplaces were characterized as hazardous, including at 52.3% of the workplaces where there was established hazard class 3.1, at 30.7% of workplaces--Class 3.2. Among all the factors of occupational environment the largest contribution into the overall assessment of working conditions was made by the lightness factor (50.9%) and non-ionizing radiation (20.6%). The most harmful working conditions have been identified for workplaces of the operator of masthead antenna, engineer of radiocommunications, broadcasting and television, electromechanician of television (radiocommunication), (broadcasting), car driver. PMID- 26856169 TI - [CHROMOSOMAL DISORDERS IN WORKERS OF CHEMICALLY HAZARDOUS ENTERPRISES WITH THE DIFFERENT HEALTH STATUS]. AB - OBJECTIVES. Chromosomal aberrations (CAs) are the one of the most sensitive biomarikers of biological effects from the hazardous environmental exposure. In this relation the comparison of cytogenetical indices in persons, exposed to the complex of factors of chemically hazard enterprises, with the presence of occupationally caused diseases seems to be very perspective for the understanding of the role of the contribution of genotoxical impact of occupational factors into staff morbidity. METHODS. Cytogenetical analysis was performed in 138 employees of chemically hazardous enterprises, including 84 patients, who need for establishment of the causation of diseases with the work in conditions of chemical plant and 54 persons without need for hospitalization according to results of the previous examination. Comparison group was consisted of 55 persons. There was performed the comparison of cytogenetical indices and commensuration of ratios of persons with individual high CAs levels and also carriers of exchange aberrations of chromosomal type in different groups of examined cases. RESULTS. There was shown statistically significant increase of the rate of CAs level including unexpectedly high level of dicentric and ring chromosomes in the group of 84 hospitalized patients. There was revealed statistically significant gain in the share of persons with CAs rate more then 5% (p < 0.01) and/or carriers of dicentrics and ring chronosomes (p < 0.5) in this group. CONCLUSION: It is possible to suggest that genotoxical impact plays a significant role in the mechanism of appearance of diseases etiologically related with the work on the enterprise of the high chemical risk. PMID- 26856170 TI - [HYGIENIC SUBSTANTIATION OF THE PREVENTION OF NUTRITION ASSOCIATED ANEMIA WITH THE AID OF FORTIFIED FERMENTED MILK BIOPRODUCT]. AB - The pilot controlled study proved the effectiveness of enriched fermented milk product "Prolacta" as means of the primary prevention of nutrition-associated anemia, firstly, at the stage of latent iron deficiency. The study included 166 adult residents of the city of Omsk. Among examined patiens there were 48 (30%) men and 118 (70%) women aged from 18 to 59 years (mean age: 29.2 +/- 0.84 years). Experimental group (79 persons) over two months took 1 glass (200 ml) of bioproduct "Prolacta" daily. The control group (87 people) no received this product neither used supplements or other vitamins and minerals. The groups were matched by gender and age. As criteria for the deviation from the normal settings there were accepted following values: the concentration of hemoglobin (Hb)--less than 130 g/l in men and less than 120 g/l in women; serum iron level--less than 12.5 umol/L, serum ferritin in men less than 95 ug/l, in women--less than 30 ug/l. The proportion of persons from the main study group with latent iron deficiency decreased from 41.8% to 25.3% (p < 0.05), the proportion of subjects with normal iron supply increased significantly (from 26.6 to 41.8%; p < 0.05). Regular consumption of fermented milk enriched with bio "Prolacta" as a means of preventing the deficiency of micronutrients and nutrition-related anemia in large extent is recommended to persons from groups at-risk (athletes, children and adolescents, and women of reproductive age). Preventive effects of this product are combined with the nutritional benefits of dairy products, its use improves the structure of nutrition of the population PMID- 26856171 TI - [HYGIENIC ASSESSMENT OF WATER-SOLUBLE VITAMINS CONTENT IN THE FOOD RATION OF ADOLESCENTS]. AB - INTRODUCTION: Adequate, balanced nutrition is a precondition for the formation of health of the younger generation. The study of the dietary intake and peculiarities of the chemical composition offood is needed to substantiate measures aimed at the correction of the ration of adolescents. PURPOSE: Hygienic evaluation of the content of water soluble vitamins in foods and the ration of teenage population of the Omsk region. TASKS OF THE STUDY: 1. To determine levels of water-soluble vitamins content in foods forming the basis of the ration of the population the Omsk region. 2. On the base of a study of the actual nutrition of adolescents to determine the levels of water-soluble vitamins consumption. 3. To give a hygienic assessment of adolescent nutrition in the Omsk region in terms of provision with water-soluble vitamins, and to identify priority directions of the alimentary correction of the revealed disorders. METHODS: The analysis of 389 food samples for the content of water-soluble vitamins (B1, B2, B6, PP C, folic acid) was performed with the use of reversed-phase HPLC high pressure on the Shimadzu LC-20 Prominence detector. The hygienic assessment of the actual nutrition of adolescents aged 13-17 years (sample survey; n = 250; 2012-2014) in the Omsk region was performed by the method of the analysis of food consumption frequency. RESULTS: There were noted significantly lower concentrations of vitamin B1 and B2 in the studied samples of cereals, bread and vegetables in comparison with reference data. Consumption levels of vitamins B1, B2, PP folic acid in the diet of adolescents in the Omsk region are lower than recommended values. In the structure of nutrition there is not enough milk dairy products--in 82.4 +/- 2.4%, fish and sea products in 90.8 +/- 1.8% of adolescents. CONCLUSION: The actual nutrition of the adolescent population of the Omsk region is irrational, unbalanced in quantitative and qualitative terms, and does not provide the necessary level of consumption of most important water-soluble vitamins. Priority for the correction nutrients there are B1, B2, folic acid (B0). PMID- 26856172 TI - [BODY COMPOSITION AND CONSUMATORY BEHAVIOR OF STUDENTS]. AB - The aim of the study was to determine indices of the anthropometric research, body composition and to evaluate the influence of consumatory behavior on the body composition of students of the medical Univercity. MATERIALS AND METHODS: In the study there were used the Dutch eating behavior questionnaire (Dutch Eating Behavior Questionnaire or DEBQ), anthropometric, bioimpedancemetric indices obtained in the survey of 101 students in the Health Centres of the city of Omsk with the use of body composition analyzer "MEDES". The representativeness of the minimal sample was calculated according to the recommendations of Plokhinskiy N.A. RESULTS: Statistical treatment of the collected data allowed to determine the average values, median, 25 and 75 percentiles, standard deviations, coefficients of variation of anthropometric, bioimpedancemetric indices, data of testing offeeding behavior offemale and male students of the Medical University, to determine the statistically significant gender differences in indices. With the help of cluster analysis of K-means in the format adopted in Statistica 6.1 there was made optimal grouping in the entire set of objects, there were identified two clusters. With the help of elements of cluster analysis there were established students included in different clusters for the implementation of personalized recommendations on hygienic education of the students. PMID- 26856173 TI - [NUTRITION AS A POSSIBLE RISK FACTOR FOR BREAST CANCER]. AB - Nutrition is an important biological factor, which affects largely on the development of the all functions of the human body. There is known association of the appearance of breast cancer with alimentary factors: inadequate consumption of fruits, vegetables, dairy products, excessive consumption of coffee, tea, sugar, salt, bread, fatty foods, overweight, early age of onset and frequent alcohol consumption. AIM OF THE STUDY: To study the prevalence of risk factors for breast cancer related to nutrition in the female population of the Omsk region. METHODS: An epidemiological (observational analytical) study of "case control", which was participated by 1002 women (797 women without breast cancer; 205--with breast cancer). In the study there were used epidemiological, hygienic, sociological, statistical methods. RESULTS: Out of 13 risk factors for the development of breast cancer related to nutrition, for female residents of the Omsk region there were confirmed their importance: a significant consumption of black tea (OR: 5,182, CI: 95% 3,721 / 7,218), an early age of onset of alcohol consumption (OR: 4,832, CI: 95% 3,477 / 6,715), overweight (OR: 1,440, CI 95% 1,005 / 2,062). Such factors as low consumption of fruit and dairy products, increased consumption of fats with high content of cholesterin, salt and coffee failed to confirm their relevance. CONCLUSION: In the female population of the Omsk region the leading risk factors for development of breast cancer related to diet, are: excessive consumption of black tea, early age of onset of alcohol use, high body mass index. PMID- 26856174 TI - [STUDY OF GLUTATHIONE AND ENZYMES OF ITS METABOLISM UNDER THE INFLUENCE OF ENRICHED DAIRY PRODUCTS FOR PROPHYLACTIC USE IN CONDITIONS OF OXIDATIVE STRESS CAUSED BY EXCESSIVE EXERCISE]. AB - There was performed the study of the activity of the antioxidant system of glutathione under regular taking of enriched with micronutrients dairy products "Bifidin " and "Prolacta" in conditions ofsimulation of xcessive exercise loads. Target of research: white outbred male rats weighing 180-200 g (n = 68). Research methods and equipment: information retrieval, biochemical, and statistical. In the subacute experiment there was established that in conditions of excessive exercise loads (CEEL) the body of the rat meets with significant oxidative stress, causing the suppression of the activity of glutathione system: the number of reduced glutathione and the activity of selenium-dependent glutathione peroxidase decline. Regular taking of dairy products "Bifidin" and "Prolacta" in conditions of CEEL (active training process) allows effectively to neutralize lipid peroxidation processes and normalize indices of the system of glutathione. There is established an increase in the activity ofglutathione-S-transferase in the homogenates of liver tissue in the simulation CEEL in combination with the use ofproduct "Bifidin". PMID- 26856175 TI - [HYGIENIC ASSESSMENT OF THE LIPID COMPONENT IN THE STRUCTURE OF NUTRITION OF STUDENT YOUNG ADULTS]. AB - The actual nutrition of the Omsk University students aged 18-27 years, was studied with the use of the method of the analysis of the frequency of food consumption. There is done quantitative assessment of nutrient consumption related to the fat component of food. There is described the qualitative composition of lipids and its effect on indices of the nutritional status assessed with the use of somatometric, bioelectric impedance and laboratory methods. The nutrition of students is established to be irrational, unbalanced on the lipid component and creates conditions for the formation of diseases with alimentary dietary risk factors. Traditional indices of nutritional status (BMI, W/HR) at this are within the boundaries of normal values, but the composition of the body under the influence of an excess of animal fats with a deficiency of essential polyunsaturated fatty acids is altering that can be diagnosed with the aid of bioimpedance measuring method. There are established correlation relations between the parameters ofconsumption of dietary lipids and indices of the nutritional status in young adults. PMID- 26856176 TI - [HYGIENIC SUBSTANTIATION OF NUTRITIONAL PREVENTION OF HYPOVITAMINOSIS B9 AND B12 IN THE POPULATION OF THE OMSK REGION]. AB - The aim of the study--the assessment of the prevalence of hypovitaminoses B9 (folic acid) and B12 in the population of the city of Omsk and the determination of the possibility of their nutritional prevention. The subject of study--the adult population (18-59 years). The actual nutrition was studied by method of analysis of the frequency of food consumption. Prevalence of hypovitaminoses B9 and B12 was estimated upon the results of laboratory tests of blood by immunochemiluminiscent methods. Established prevalence of hypovitaminoses B (folic acid) and B12 in the population of the city of Omsk accounted for 63.2 +/- 5.8% and 13.2 +/- 4.1%, respectively. There was shown the possibility of correction of supply with vitamins by means of regular taking offermented dairy product "Prolacta". The serum content of vitamin B12 after a 2-month course of daily use of the product was increased by 17.8%, and the serum folate content--by 29.1%. The proportion of cases with insufficient content ofvitamin B9 in the experimental group decreased from 80.0 +/- 6.8% to 38.7 +/- 8.7%. PMID- 26856177 TI - [ROLE OF FACTORS OF THE ENVIRONMENT OF EDUCATION AND TRAINING IN THE FORMATION OF THE DYSPLASIA OF THE CONNECTIVE TISSUE IN TEENAGE YEARS]. AB - Negative trends of indices of the incidence in children and teenagers in the Russian Federation are caused by essential changes in the system of training and medical care of school students. In cases of connective tissue dysplasia (CTD) when the gene defect is remains to be unascertained, there is a great role of environmental factors contributing to the implementation of pathology and hygienic measures of the prevention of complications. There was performed the hygienic assessment of sanitary-epidemiologic welfare (SEW) of the educational institutions (EI) of the city of Omsk (n = 76), including the study of environmental factors, health and performance of adolescents. For the correction priority factors for SEW were "medical care", "mode and organization of the educational-training process", "conditions and organization of nutrition", "conditions and organization of physical education." There are determined the most important for the occurrence of CTD indices lifestyle factors and "indicators" of the risk for the progression of pathological processes in adolescents. PMID- 26856178 TI - [COMPREHENSIVE ASSESSMENT OF HEALTH IN BABIES OF EARLY PRESCHOOL AGE]. AB - Health of the children's population is one of the most important components of safety of the country. The incidence level in children of early age reflects an interaction of economic, ecological, social and hygienic and medico organizational factors in society. The issue of the paper is the comprehensive assessment of health of children of the first three years of life upon indices of the morbidity rate, physical development, interrelation of given indices with the structure of the family and their social status. Indices of the physical development of boys in the all age groups exceeded the corresponding indices in girls (p < 0.05). There was also statistically significant and augmentation of indices of body weights of children along with the age (p < 0.05). The highest morbidity rate in children was established in the first year of life, the minimal one--in the third year. In the all age groups diseases of respiratory organs prevailed, at this their proportion in the total amount of diseases in the third year of life considerably exceeded the same in first and second years of life. The highest incidences of children took place in the families formed by juvenile and lonely women. Diseases of digestive organs in the second and third years of life in children from juvenile and lonely mothers were considerably enlarged on frequency (by 1,4-1,7 times), infectious and parasitic diseases (by 1,1-1,7 times) in comparison with children from full families. In the all studied types offamilies and age groups the state of health of children was worse, than in full families. There was substantiated the development of the multilevel system for the prophylaxis of losses of health in children at early preschool age. PMID- 26856179 TI - [HEALTH RISK ASSESSMENT OF THE CHILD POPULATION IN THE CONSUMPTION OF TAP WATER WITH ACCOUNT OF ITS SECONDARY POLLUTION]. AB - Work was performed within the framework of the State program of competitive recovery of Kazan (Volga) Federal University among the world's leading research and education centers and subsidies allocated to Kazan Federal University for the implementation of Public task in the field of scientific activities. In the paper there are presented results of the risk assessment for children's health, with allowances made for evolving cationic-anionic pattern of tap waters while moving along pipelines and distributing networks, discriminatingly on study area. The population health risk assessment was performed according to public health regulatory methods P 2.1.10.1920-04 in relation to the ionic composition of tap water consumed by children's population of the city of Kazan. The use of a risk assessment in consumption of tap water by the most susceptible population group with localized residence allows to identify zones in the boundaries of the urban area in which water is needed post-treatment of tap waters flowing to consumers. PMID- 26856180 TI - [HYGIENIC SUBSTANTIATION OF THE DEVELOPMENT AND USE OF POLYGUANIDINES AS ANTIMICROBIAL PROPHYLACTIC MEANS OF THE INNOVATIVE CLASS]. AB - In the article there are presented data of the system analysis of hygienic properties of polyguanidines (PAG) as an innovative class of domestic microbicidal chemical long-acting compounds synthesized in the domestic scientific institution--Institute ofenvironmental and technological problems, and also delivered on their base new disinfectants. Submitted proceedings of microbiological studies indicate to the antimicrobial action of PA G against Gram negative and Gram-positive bacteria, viruses, dermatophytes, yeasts, fungi, including pathogens, as well infectious agent of swine and legionellosis. The data of toxicological studies of PAG and a number of derivative disinfectants justify their hygienic safety in dependence on the chemical nature of the used anion (A), the composition and structure of the polymer chain and also the content of residual monomers. All this characterizes PAG as a very promising group of compounds for the use in the form of independent disinfectants and as antimicrobial additives and auxiliaries in such means for different purposes. PMID- 26856181 TI - The South Has Risen Again: Thoughts on the Tea Party and the Recent Rise of Right Wing Racism. AB - This paper examines the significance of racism in fueling the recent rise of the Tea Party and related Right-Wing political groups and activity. It briefly explores some of the history of racism in this country that has been directed toward African Americans and how it has influenced political developments from Colonial times to the present. It suggests that this racist resurgence can be seen, in part, as a re-enactment of the trauma of the Civil War by the descendants, and those who identify with them, who were on the losing side of that conflict. PMID- 26856182 TI - Psychohistory and Family Among Antebellum Slaveholders. AB - This article examines the macroscopic reasons for maternal rage and its injection into slaveholder children in the antebellum South. It is argued that the misogyny that infected antebellum life metastasized in southern mistresses and affected the way they felt about themselves and their children. As mothers, they were casual parents, concerned with molding the character of their charges, rearing warriors and proper ladies, but uninterested in caring for them and helping them realize their own aspirations. It is argued that the misanthropic rage that they injected into their children constituted the poison that each generation of slaveholders had to ventilate into poison containers, slaves, as a homeostatic means of psycho-emotional survival. This intergenerational process of poison injection--from father to mother, from mother to child, from child to slave, constituted the process that insured the perpetuation of the psychic structure necessary for the continuation of slavery from generation to generation. PMID- 26856183 TI - Transformations in Emotional Structures Throughout History. AB - Today, in my view, we can on the basis of the psychohistorical research understand the dynamic line of historical processes, and in particular the process of the development of our modern way of viewing the world. I try to describe in this development by bringing together European and American psychohistorical research. A deeper understanding of the psychic and social dimensions of historical development can be a resource for political action. In the global world it is important to both manage the mutual dealings between diverse cultural regions and support constructive interactions. This is only possible when the internal dynamics and the individual characteristics of the cultural developments in the regions can be taken into account. At the present stage of discussion, which talks of a "clash of cultures" and ultimately ends in military intervention, it is blatantly obvious that every potential for understanding and dealing relevantly with each other, should be exploited as provided for by the contributions of psychohistory. PMID- 26856184 TI - PREFACE. Britain's Bastard Child. PMID- 26856185 TI - Remarks on Latency: Onset in Different Cultures. AB - The features of cultural identity in latency-age children along with the influences of cultural values, transmitted via the family, are the central focus of this essay. In this context, the understanding of how development can appear to bifurcate along a continuum of "individualist" versus "collectivist" cultures can be perceived in what Andreas-Salome referred to as the "dual orientation of narcissism". This essay also discusses the impact of immigration and the adaptation of the individual in a foreign country. PMID- 26856186 TI - The Whats and Whys of Modern Romance. PMID- 26856187 TI - Bioanalytical techniques in nontargeted clinical lipidomics. AB - Lipidomic analysis aims at comprehensive characterization of molecular lipids in biological systems. Due to the central role of lipid metabolism in many devastating diseases, lipidomics is being increasingly applied in biomedical research. Over the past years, advances in analytical techniques and bioinformatics enabled increasingly comprehensive and accurate coverage of lipids both in tissues and biofluids, yet many challenges remain. This review highlights recent progress in the domain of analytical lipidomics, with main emphasis on non targeted methodologies for large scale clinical applications, as well as discusses some of the key challenges and opportunities in this field. PMID- 26856188 TI - Tc-99m Glu-Cys-Gly-His-Gly-Lys (ECG-HGK), a novel Tc-99m labeled hexapeptide for molecular tumor imaging. AB - Domain 5 of kinin-free high molecular weight kininogen inhibits the adhesion of many tumor cell lines, and it has been reported that the histidine-glycine-lysine (HGK)-rich region might be responsible for inhibition of cell adhesion. The authors developed HGK-containing hexapeptide, glutamic acid-cysteine-glycine (ECG)-HGK, and evaluated the utility of Tc-99m ECG-HGK for tumor imaging. Hexapeptide, ECG-HGK was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated. The uptake of Tc-99m ECG-HGK within HT 1080 cells was evaluated in vitro. In HT-1080 tumor-bearing mice, gamma imaging and biodistribution studies were performed. The complexes Tc-99m ECG-HGK was prepared in high yield. The uptake of Tc-99m ECG-HGK within the HT-1080 tumor cells had been demonstrated by in vitro studies. The gamma camera imaging in the murine model showed that Tc-99m ECG-HGK was accumulated substantially in the HT 1080 tumor (tumor-to-muscle ratio = 5.7 +/- 1.4 at 4 h), and the tumoral uptake was blocked by the co-injection of excess HGK (tumor-to-muscle ratio = 2.8 +/- 0.6 at 4 h). In the present study, Tc-99m ECG-HGK was developed as a new tumor imaging agents. Our in vitro and in vivo studies revealed specific function of Tc 99m ECG-HGK for tumor imaging. PMID- 26856190 TI - Analysis of medieval mtDNA from Napole cemetery provides new insights into the early history of Polish state. AB - Contemporary historical anthropology and classical archaeology are concerned not only with such fundamental issues as the origins of ancient human populations and migration routes, but also with the formation and development of inter-population relations and the mixing of gene pools as a result of inter-breeding between individuals representing different cultural units. The contribution of immigrants to the analysed autochthonous population and their effect on the gene pool of that population has proven difficult to evaluate with classical morphological methods. The burial of one individual in the studied Napole cemetery located in central Poland had the form of a chamber grave, which is typical of Scandinavian culture from that period. However, this fact cannot be interpreted as absolute proof that the individual (in the biological sense) was allochtonous. This gives rise to the question as to who was actually buried in that cemetery. The ancient DNA results indicate that one of the individuals had an mtDNA haplotype typical of Iron Age northern Europe, which suggests that he could have arrived from that area at a later period. This seems to indirectly confirm the claims of many anthropologists that the development of the early medieval Polish state was significantly and directly influenced by the Scandinavians. PMID- 26856189 TI - The voluntary driven exoskeleton Hybrid Assistive Limb (HAL) for postoperative training of thoracic ossification of the posterior longitudinal ligament: a case report. AB - CONTEXT: The hybrid assistive limb (HAL) is a wearable robot suit that assists in voluntary control of knee and hip joint motion by detecting bioelectric signals on the surface of the skin with high sensitivity. HAL has been reported to be effective for functional recovery in motor impairments. However, few reports have revealed the utility of HAL for patients who have undergone surgery for thoracic ossification of the posterior longitudinal ligament (thoracic OPLL). Herein, we present a postoperative thoracic OPLL patient who showed remarkable functional recovery after training with HAL. FINDINGS: A 63-year-old woman, who could not walk due to muscle weakness before surgery, underwent posterior decompression and fusion. Paralysis was re-aggravated after the initial postoperative rising. We diagnosed that paralysis was due to residual compression from the anterior lesion and microinstability after posterior fixation, and prescribed bed rest for a further 3 weeks. The incomplete paralysis gradually recovered, and walking training with HAL was started on postoperative day 44 in addition to standard physical therapy. The patient underwent 10 sessions of HAL training until discharge on postoperative day 73. Results of a 10-m walk test were assessed after every session, and the patient's speed and cadence markedly improved. At discharge, the patient could walk with 2 crutches and no assistance. Furthermore, no adverse events associated with HAL training occurred. CONCLUSION: HAL training for postoperative thoracic OPLL patients may enhance improvement in walking ability, even if severe impairment of ambulation and muscle weakness exist preoperatively. PMID- 26856191 TI - A randomized controlled trial to evaluate the lung clearance index as an outcome measure for early phase studies in patients with cystic fibrosis. AB - BACKGROUND: Outcome measures that can evaluate treatment efficacy are important to enhance development of new therapeutic agents for Cystic Fibrosis (CF). We investigated whether the lung clearance index (LCI) measured by multiple breath washout (MBW) can detect a treatment effect of hypertonic saline (HS) inhalation after single dosing within a 24 h period. METHODS: In this randomized controlled cross-over trial, CF patients received inhalation of HS and isotonic saline (IS). MBW and spirometry were performed at 5 time points over 24 h. LCI was measured using both a nitrogen washout technique (LCIN2) and sulfur hexafluoride as a tracer gas (LCISF6). The primary endpoint was the change in the LCIN2 between baseline and 24 h. Secondary endpoints included change in LCISF6 and spirometry outcomes. RESULTS: Twenty-one patients were randomized. Sixteen completed all study visits and all time point measurements. Eighteen patients contributed to the intention to treat analysis. Significant changes were not detected for either LCI or the spirometry outcomes. However, the primary outcome parameter (change in LCI between the baseline visits and 24 h after inhalation) demonstrated a trend towards improved LCI, in the HS treatment arm compared with the IS treatment arm, -0.60 LCIN2 (SE 0.32), p = 0.08); similar trends were not observed for spirometric measures. The overall effect size of HS was smaller than in previous studies of longer duration. CONCLUSIONS: These data suggest that LCI may potentially be used as an outcome measure in early phase trials with therapeutic agents that have a larger treatment effects than a single inhalation of HS. PMID- 26856193 TI - Comment on "Serum magnesium and not vitamin D is associated with better QoL in COPD: A cross-sectional study". PMID- 26856192 TI - The generalizability of bronchiectasis randomized controlled trials: A multicentre cohort study. AB - INTRODUCTION: Randomized controlled trials (RCTs) for bronchiectasis have experienced difficulties with recruitment and in reaching their efficacy end points. To estimate the generalizability of such studies we applied the eligibility criteria for major RCTs in bronchiectasis to 6 representative observational European Bronchiectasis cohorts. METHODS: Inclusion and exclusion criteria from 10 major RCTs were applied in each cohort. Demographics and outcomes were compared between patients eligible and ineligible for RCTs. RESULTS: 1672 patients were included. On average 33.0% were eligible for macrolide trials, 15.0% were eligible for inhaled antibiotic trials, 15.9% for the DNAse study and 47.7% were eligible for a study of dry powder mannitol. Within these groups, some trials were highly selective with only 1-9% of patients eligible. Eligible patients were generally more severe with higher mortality during follow-up (mean 17.2 vs 9.0% for macrolide studies, 19.2%% vs 10.7% for inhaled antibiotic studies), and a higher frequency of exacerbations than ineligible patients. As up to 93% of patients were ineligible for studies, however, numerically more deaths and exacerbations occurred in ineligible patient across studies (mean 56% of deaths occurred in ineligible patients across all studies). CONCLUSION: Our data suggest that patients enrolled in RCT's in bronchiectasis are only partially representative of patients in clinical practice. The majority of mortality and morbidity in bronchiectasis occurs in patients ineligible for many current trials. PMID- 26856194 TI - Efficacy and Safety of Electronic Cigarettes for Smoking Cessation: A Critical Approach. PMID- 26856195 TI - Smoking Cessation Support Services at Community Pharmacies in the UK: A Systematic Review. PMID- 26856196 TI - Advanced Role and Field of Competence of the Physical and Rehabilitation Medicine Specialist in Contemporary Cardiac Rehabilitation. PMID- 26856197 TI - Left Atrial Volumetric and Strain Analysis by Three-Dimensional Speckle-Tracking Echocardiography in Noncompaction Cardiomyopathy: Results from the MAGYAR-Path Study. AB - INTRODUCTION: Noncompaction cardiomyopathy (NCCM) is a rare congenital cardiomyopathy characterised by a distinctive 2-layered appearance of the myocardium due to hypertrabecularisation and deep intertrabecular recesses. The present study was designed to assess left atrial (LA) volumes and volumetric and strainbased functional properties by three-dimensional speckle-tracking echocardiography (3DSTE) in NCCM. METHODS: The study included 12 consecutive NCCM patients. Their results were compared to 20 age- and sex-matched healthy controls. Complete two-dimensional Doppler echocardiography and 3DSTE were performed in all cases. RESULTS: Calculated LA maximum (76.5 +/- 26.8 mL vs. 45.3 +/- 15.1 mL, p=0.0002) and minimum (56.9 +/- 27.3 mL vs. 25.3 +/- 15.2 mL, p=0.0002) volumes and LA volume before atrial contraction (67.1 +/- 28.2 mL vs. 35.7 +/- 16.4 mL, p=0.0004) were significantly greater in NCCM patients. Total, active, and passive LA emptying fractions proved to be smaller in NCCM. Peak global radial (-9.3 +/- 7.8% vs. -16.8 +/- 10.2%, p=0.05), circumferential (12.8 +/- 8.4% vs. 26.2 +/- 9.2%, p=0.0003), longitudinal (12.8 +/- 8.2% vs. 22.5 +/- 8.5%, p=0.004), and area (26.7 +/- 18.5% vs. 51.6 +/- 20.3%, p=0.001) strains were significantly smaller in NCCM patients as compared to matched controls. CONCLUSIONS: Significantly greater LA volumes and compromised LA functional properties could be demonstrated by 3DSTE in patients with NCCM. PMID- 26856198 TI - The Pivotal Role Of Studying The Left Atrium By Speckle Tracking In Heart Failure. PMID- 26856199 TI - Complications Related to Cardiac Rhythm Management Device Therapy and Their Financial Implication: A Prospective Single-Center TwoYear Survey. AB - INTRODUCTION: Cardiac rhythm management devices (CRMDs) have proven their clinical effectiveness for patients with heart rhythm disorders. Little is known about safety and complication rates during the implantation of these devices. This study demonstrated the complication rates related to CRMD implantation, and estimated the additional hospital stay and cost associated with the management of complications. METHODS: During a period of one year, a total of 464 consecutive recipients underwent CRMD implantation and were followed for 2 years. Finally, data were analyzed for 398 patients who completed the two-year follow up, resulting in a total of 796 patient-years. RESULTS: Of the 201 patients with initial pacemaker (PM) implantations, 6 (2.99%) had seven complications (5 patients had lead dislodgement, 1 of them twice), and 1 patient developed pocket infection. Of the 117 PM replacements, 1 (0.85%) patient developed a complication (pocket erosion). Two patients with complications (1 with an initial PM and 1 with a replacement) died before completing the follow up for reasons unrelated to cardiac causes. There were no complications in either initial implantations (69 patients) or replacements (11 patients) of implantable cardioverter defibrillators. The average prolongation of the hospital stay was 7 days, ranging from 1 to 35 days, resulting in 17,411 of total additional direct hospital costs. CONCLUSION: This study found relatively low rates of complications in patients undergoing CRMD implantation, initial or replacement, in our center, compared with other studies. The additional hospitalization days and costs attributable to these complications depend on the nature of the complication. PMID- 26856200 TI - The Burden of Cardiac Rhythm Management Complications. PMID- 26856201 TI - A Tricky Percutaneous Paravalvular Leak Closure Two Years After Implantation of 3f Enable Sutureless Bioprosthetic Aortic Valve. AB - Sutureless valves were designed in an attempt to simplify the aortic valve replacement procedure and reduce extracorporeal circuit time, whilst allowing complete excision of the calcified native valve using a minimally invasive approach. Elderly patients with significant comorbidities are considered to benefit the most, although randomized data are lacking. In registries of patients treated with implantation of a 3f Enable sutureless bioprosthetic aortic valve, all patients who developed paravalvular leak have been treated with valve explantation. This is the first case report describing a tricky yet successful percutaneous paravalvular leak closure 2 years after implantation of a 3f Enable sutureless aortic bioprosthesis. PMID- 26856202 TI - Haddad Syndrome. AB - Congenital central hypoventilation syndrome (CCHS) causes predominantly sleep apnoea and is one of a growing number of inherited disorders characterised by autonomic nervous system dysfunction/dysregulation (ANSD). In association with Hirschsprung's disease (HSCR), it presents as Haddad's syndrome. We report a case of Haddad's syndrome complicated by sinus node dysfunction. PMID- 26856203 TI - Primary Angioplasty with Manual Thrombectomy Alone as a Therapeutic Strategy in a Patient with Acute Myocardial Infarction and Severe Anemia. PMID- 26856204 TI - Ablation of Cavotricuspid Isthmus-Dependent Flutter Using a Mini-Electrode Equipped 8-mm Ablation Catheter: Case Series. PMID- 26856206 TI - Obesity and Acute Coronary Syndromes. PMID- 26856205 TI - An ECG Diagnosis Only for the Cold-Hearted. PMID- 26856207 TI - Smoking Cessation and Health Economics. PMID- 26856208 TI - Total Synthesis of a Diacetonide Derivative of Thuggacin A. AB - A highly stereoselective total synthesis of the diacetonide derivative of the antibiotic thuggacin A has been described. The synthesis features the stereoselective Stille cross-coupling reaction to set up the whole carbon framework, aldol condensation to construct the highly substituted conjugated diene, non-Evans syn aldol, CBS reduction, Hantzsch's thiazole synthesis, Horner Wadsworth-Emmons reaction, and Shiina's macrolactonization. PMID- 26856209 TI - Non-eligibility for reperfusion therapy in patients presenting with ST-segment elevation myocardial infarction: Contemporary insights from the National Cardiovascular Data Registry (NCDR). AB - BACKGROUND: Reperfusion therapy is lifesaving in patients presenting with ST segment elevation myocardial infarction (STEMI). Contemporary data describing the characteristics and outcomes of patients presenting with STEMI not receiving reperfusion therapy are lacking. METHODS: Using the ACTION Registry-GWTG database, we examined 219,726 STEMI patients (January 2007-December 2013) at 721 percutaneous coronary intervention (PCI)-capable hospitals in United States. Clinical characteristics and in-hospital outcomes were stratified by those who underwent reperfusion (n = 188,200; 86%), those who did not undergo reperfusion with a reason for ineligibility (n = 27,179; 12%), and those without reperfusion but had no reason for ineligibility (n = 4,347; 2%). RESULTS: Compared with STEMI patients receiving reperfusion therapy, the nonreperfusion groups were older, were more often female, and had higher rates of hypertension, diabetes, prior myocardial infarction, prior stroke, atrial fibrillation, and left bundle-branch block and heart failure on presentation. The major reason for reperfusion noneligibility was coronary anatomy not suitable for PCI (33%). Presence of 3 vessel coronary disease was more common in the nonreperfusion groups (with or without a documented reason) compared with reperfusion group (38% and 36% vs 26%, P < .001, respectively). In-hospital mortality was higher in patients not receiving reperfusion therapy with or without a documented reason compared with the reperfusion group (adjusted odds ratio [95% CI] 1.88 [1.78-1.99] and 1.37 [1.21-1.57], respectively). CONCLUSION: Most patients with STEMI not receiving reperfusion therapy had a documented reason. Coronary anatomy not suitable for PCI was the major contributor to ineligibility. In-hospital mortality was higher in patients not receiving reperfusion therapy. PMID- 26856210 TI - Multivessel vs culprit-only percutaneous coronary intervention among patients 65 years or older with acute myocardial infarction. AB - BACKGROUND: Older adults presenting with acute myocardial infarction (MI) often have multivessel coronary artery disease amenable to percutaneous coronary intervention (PCI), yet the risks of multivessel intervention may outweigh potential benefits in these patients. We sought to determine if nonculprit intervention during the index PCI is associated with better outcomes among older patients with acute MI and multivessel disease. METHODS: We examined 19,271 ST segment elevation MI (STEMI) and 31,361 non-STEMI (NSTEMI) patients 65years or older with multivessel disease in a linked CathPCI Registry-Medicare database, excluding patients with prior coronary artery bypass grafting, left main disease, or cardiogenic shock. Using inverse probability-weighted propensity adjustment, we compared mortality between patients receiving culprit-only vs multivessel intervention during the index PCI procedure. RESULTS: Most older MI patients (91% STEMI and 74% NSTEMI) received culprit-only intervention during the index PCI. Among STEMI patients, multivessel intervention during the index PCI was associated with higher 30-day mortality (8.3% vs 6.3%, adjusted hazard ratio [HR] 1.36, 95% CI 1.14-1.62) than culprit-only intervention, and this trend persisted at 1year (13.8% vs 12.2%, adjusted HR 1.14, 95% CI 0.99-1.31). No significant mortality differences were observed among NSTEMI patients at 30days (3.4% vs 4.1%, adjusted HR 1.01, 95% CI 0.88-1.15) or at 1year (10.1% vs 10.8%, adjusted HR 0.99, 95% CI 0.91-1.08). CONCLUSIONS: Nonculprit intervention during the index PCI was associated with worse outcomes among STEMI patients, but not NSTEMI patients. PMID- 26856211 TI - Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS): Rationale and design of a prospective randomized multicenter study. AB - BACKGROUND: Atrial fibrillation (AF) is estimated to account for approximately every fifth ischemic stroke. In routine clinical practice, detection of undiagnosed, clinically silent AF represents a major diagnostic challenge, and in up to 30% of patients with ischemic stroke, AF remains undetected. The MonDAFIS study has been designed to quantify the diagnostic yield and clinical relevance of systematic electrocardiogram (ECG) monitoring for patients with acute ischemic stroke during the subsequent in hospital stay. STUDY DESIGN: A prospective randomized multicenter study in 3,470 patients with acute ischemic stroke or transient ischemic attack and without known AF on hospital admission. Over a period of approximately 2years, patients will be enrolled in about 30 German certified stroke units and randomized 1:1 to receive either usual stroke unit diagnostic procedures for detection of AF (control group) or usual stroke unit diagnostic procedures plus standardized and centrally analyzed Holter ECG recording for up to 7days in hospital (intervention group). Results of the ECG core laboratory analysis will be provided to the patients and treating physicians. All patients will be followed up for treatment and cardiovascular outcomes at 6, 12, and 24months after enrollment. OUTCOMES: The primary outcome of the randomized MonDAFIS study is the proportion of patients who receive anticoagulation therapy 12months after the index stroke. Secondary outcomes include the number of stroke patients with newly detected AF in hospital and the rate of recurrent stroke, major bleedings, myocardial infarction, or death 6, 12, and 24months after the index event. MonDAFIS will also explore patient-reported adherence to anticoagulants, the clinical relevance of short atrial tachycardia, or excessive supraventricular ectopic activity as well as cost-effectiveness of prolonged, centrally analyzed ECG recordings. CONCLUSION: MonDAFIS will be the largest study to date to evaluate whether a prolonged and systematic ECG monitoring during the initial in hospital stay has an impact on secondary stroke prevention. In addition, prognosis as well as adherence to medication up to 2 years after the index stroke will be analyzed. The primary results of the MonDAFIS study may have the potential to change the current guidelines recommendations regarding ECG workup after ischemic stroke. PMID- 26856212 TI - The role of diabetes mellitus in the composition of coronary thrombi in patients presenting with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. AB - BACKGROUND: Although diabetes mellitus (DM) is a predictor of poor outcomes in patients with ST-segment elevation myocardial infarction (STEMI), few studies have analyzed the impact of DM on the constituency of coronary thrombi. OBJECTIVES: Comparing morphologic and histopathologic aspects of coronary thrombi in STEMI patients with and without DM who underwent primary percutaneous coronary intervention. METHODS: All consecutive patients with STEMI admitted to our institution between April 2010 and December 2012 (n = 1,548) were considered for inclusion. Thrombus material was obtained by aspiration thrombectomy; morphologic and histopathologic aspects were assessed by 3 independent pathologists blinded to clinical characteristics and outcomes. Patients with DM were compared with those without DM. A sensitivity analysis was performed using a propensity score. RESULTS: During the study period, coronary thrombi material from 259 patients was obtained, of whom 19% (n = 49) had diabetes. Diabetic patients were older (P = .10), had a higher frequency of hypertension (P < .01) and dyslipidemia (P = .03), and had a trend to a longer time from the onset of chest pain to hospital arrival (P = .08). The number of retrieved fragments, the size of the thrombi and its composition (leukocytes, fibrin, and erythrocytes percent), and thrombus age and color were similar between patients with or without DM. There were also no statistically significant differences in thrombus constituency of the propensity score-matched patients (n = 92). CONCLUSIONS: In this study, morphologic and histopathologic constituency of coronary thrombi in the setting of a ST-elevation myocardial infarction was not significantly different between patients with or without DM. This finding was intriguing and deserves further investigation. PMID- 26856214 TI - Reduction of ischemic events in Improved Reduction of Outcomes: Vytorin Efficacy International Trial: Intensive cholesterol lowering or ezetimibe antithrombotic effects? PMID- 26856213 TI - Evaluation of a provocative dyspnea severity score in acute heart failure. AB - BACKGROUND: The acute heart failure (AHF) Syndromes International Working Group proposed that dyspnea be assessed under standardized, incrementally provocative maneuvers and called for studies to assess the feasibility of this approach. We sought to assess the feasibility and statistical characteristics of a novel provocative dyspnea severity score (pDS) versus the traditional dyspnea visual analog scale (DVAS) in an AHF trial. METHODS: At enrollment, 24, 48 and 72hours, 230 ROSE-AHF patients completed a DVAS. Dyspnea was then assessed with 5-point Likert dyspnea scales administered during 4 stages (A: upright-with O2, B: upright-without O2, C: supine-without O2 and D: exercise-without O2). Patients with moderate or less dyspnea were eligible for the next stage. RESULTS: At enrollment, oxygen withdrawal and supine provocation were highly feasible (>=97%), provoking more severe dyspnea (>=1 Likert point) in 24% and 42% of eligible patients, respectively. Exercise provocation had low feasibility with 38% of eligible patients unable to exercise due to factors other than dyspnea. A pDS was constructed from Likert scales during the 3 feasible assessment conditions (A-C). Relative to DVAS, the distribution of the pDS was more skewed with a high "ceiling effect" at enrollment (23%) limiting sensitivity to change. Change in pDS was not related to decongestion or 60-day outcomes. CONCLUSIONS: Although oxygen withdrawal and supine provocation are feasible and elicit more severe dyspnea, exercise provocation had unacceptable feasibility in this AHF cohort. The statistical characteristics of a pDS based on feasible provocation measures do not support its potential as a robust dyspnea assessment tool in AHF. PMID- 26856215 TI - Computer-guided normal-low versus normal-high potassium control after cardiac surgery: No impact on atrial fibrillation or atrial flutter. AB - INTRODUCTION: This study was designed to determine the effect of 2 different potassium regulation strategies with different targets (within the reference range) on atrial fibrillation (AF) or atrial flutter (AFL) in a cohort of intensive care unit patients after cardiac surgery. METHODS: The GRIP-COMPASS study was a prospective double-blinded interventional study in 910 patients after cardiac surgery (coronary artery bypass grafting and/or valvular surgery). Patients were assigned to either the normal-low potassium target (nLP group, 4.0 mmol/L) or the normal-high potassium target (nHP group, 4.5 mmol/L) in alternating blocks of 50 patients. Potassium levels were regulated using a validated computer-assisted potassium replacement protocol (GRIP-II). The primary end point was the incidence of AF/AFL on a 12-lead electrocardiogram during the first postoperative week. RESULTS: Of the 910 patients, 447 were assigned to the nLP group; and 463, to the nHP group, with no baseline differences between the 2 groups. The mean daily administered dose of potassium was 30 +/- 23 mmol (nLP) versus 52 +/- 27 mmol (nHP) (P < .001), which resulted in mean intensive care unit potassium concentration of 4.22 +/- 0.36 mmol/L and 4.33 +/- 0.34 mmol/L, respectively (P < .001). The incidence of AF/AFL after cardiac surgery did not differ: 38% in the nLP group and 41% in the nHP group. Also in several subgroups (eg, patients not known with prior AF/AFL or with valve surgery), there were no differences. CONCLUSIONS: There were no differences in incidence of AF/AFL with 2 potassium regulation strategies with different potassium targets and different amounts of potassium administered in patients after cardiac surgery. PMID- 26856217 TI - Supporting open access to clinical trial data for researchers: The Duke Clinical Research Institute-Bristol-Myers Squibb Supporting Open Access to Researchers Initiative. AB - There are growing calls for sponsors to increase transparency by providing access to clinical trial data. In response, Bristol-Myers Squibb and the Duke Clinical Research Institute have collaborated on a new initiative, Supporting Open Access to Researchers. The aim is to facilitate open sharing of Bristol-Myers Squibb trial data with interested researchers. Key features of the Supporting Open Access to Researchers data sharing model include an independent review committee that ensures expert consideration of each proposal, stringent data deidentification/anonymization and protection of patient privacy, requirement of prespecified statistical analysis plans, and independent review of manuscripts before submission for publication. We believe that these approaches will promote open science by allowing investigators to verify trial results as well as to pursue interesting secondary uses of trial data without compromising scientific integrity. PMID- 26856216 TI - Trends in hospitalization for takotsubo cardiomyopathy in the United States. AB - BACKGROUND: Takotsubo (or stress induced) cardiomyopathy is characterized by transient left ventricular systolic dysfunction. Recent trends in patient volume, characteristics, and outcomes in the United States are unknown. METHODS: Using 2007-2012 National Inpatient Sample data, we identified 22,005 adults (>=18 years) with a primary and 31,942 adults with a secondary discharge diagnosis of takotsubo cardiomyopathy (International Classification of Diseases, Ninth Revision, code 429.83) who underwent diagnostic coronary angiography. RESULTS: During 2007 to 2012, the incidence of takotsubo cardiomyopathy increased over 3 fold: 52/million discharges in 2007 to 178/million in 2012 (P < .001). We found a temporal increase in the prevalence of cardiac arrest, cardiogenic shock, cardiovascular risk factors (diabetes, hypertension), and psychiatric disorders (P trend < .0001 for all). In-hospital mortality was 1.1% and remained unchanged over this period (P = .22). Compared to the primary diagnosis group, mortality in the secondary diagnosis group was higher (1.1% vs 3.2%) and was associated with higher incidence of cardiogenic shock, cardiac arrest, and respiratory failure. Men represent 8% of patients in the primary diagnosis group and 12% in the secondary group. In both groups, men had a higher incidence of shock, cardiac arrest, and respiratory failure. Although their mortality was higher than women in the primary group (3.0% vs 0.9%, adjusted odds ratio 3.85, 1.74-8.51), it was comparable in the secondary group (4.8% vs 3.0%). CONCLUSIONS: We found a marked increase in the hospitalization for takotsubo cardiomyopathy in the United States in recent years, suggesting higher incidence than prior reports. Although outcomes have remained favorable, there is an increasing burden of cardiovascular and psychiatric disorders in this population with growing cost of care. Risk of mortality is higher in men and in patients with underlying critical illness. The excess mortality in these groups appears to be mediated by greater severity of disease. PMID- 26856218 TI - Practice gaps in the care of mitral valve regurgitation: Insights from the American College of Cardiology mitral regurgitation gap analysis and advisory panel. AB - BACKGROUND: The revised 2014 American College of Cardiology (ACC)/American Heart Association valvular heart disease guidelines provide evidenced-based recommendations for the management of mitral regurgitation (MR). However, knowledge gaps related to our evolving understanding of critical MR concepts may impede their implementation. METHODS: The ACC conducted a multifaceted needs assessment to characterize gaps, practice patterns, and perceptions related to the diagnosis and treatment of MR. A key project element was a set of surveys distributed to primary care and cardiovascular physicians (cardiologists and cardiothoracic surgeons). Survey and other gap analysis findings were presented to a panel of 10 expert advisors from specialties of general cardiology, cardiac imaging, interventional cardiology, and cardiac surgeons with expertise in valvular heart disease, especially MR, and cardiovascular education. The panel was charged with assessing the relative importance and potential means of remedying identified gaps to improve care for patients with MR. RESULTS: The survey results identified several knowledge and practice gaps that may limit implementation of evidence-based recommendations for MR care. Specifically, half of primary care physicians reported uncertainty regarding timing of intervention for patients with severe primary or functional MR. Physicians in all groups reported that quantitative indices of MR severity were frequently not reported in clinical echocardiographic interpretations, and that these measurements were not consistently reviewed when provided in reports. In the treatment of MR, nearly 30% of primary care physician and general cardiologists did not know the volume of mitral valve repair surgeries by their reference cardiac surgeons and did not have a standard source to obtain this information. After review of the survey results, the expert panel summarized practice gaps into 4 thematic areas and offered proposals to address deficiencies and promote better alignment with the 2014 ACC/American Heart Association valvular disease guidelines. CONCLUSION: Important knowledge and skill gaps exist that may impede optimal care of the patient with MR. Focused educational and practice interventions should be developed to reduce these gaps. PMID- 26856219 TI - Cerebrovascular accidents after percutaneous coronary interventions from 2002 to 2014: Incidence, outcomes, and associated variables. AB - BACKGROUND: Cerebrovascular accident (CVA) and transient ischemic attack (TIA) related to percutaneous coronary intervention (PCI) are relatively rare complications, but they are associated with high morbidity and mortality. Given the evolution of both CVA risk and PCI techniques over time, this study was conducted to evaluate trends in CVA and TIA associated with PCI and to identify variables associated with neurologic events. METHODS: Consecutive patients undergoing PCI at the Washington Hospital Center between January 2002 and June 2015 were included. Prespecified data were prospectively collected, including baseline and procedural characteristics, in-hospital outcomes, and 1-year mortality. The subjects who had a CVA or TIA during or immediately after PCI were compared with those without procedure-associated CVA or TIA. RESULTS: Overall, 25,626 patients were included in the study. The mean age was 65.0 +/- 12.4 years, 16,949 (65.2%) were male, and 7,436 (28.6%) were African American. From 2002 to 2015, 110 neurologic events post-PCI were diagnosed (0.43%); this included 86 CVAs (0.34%) and 24 TIAs (0.09%). The annual rate of postprocedural neurologic events was 0.42% +/- 0.12%. There were significant changes in baseline risk factors over time, with increasing age, incidence of insulin-dependent diabetes, and chronic kidney disease. Patients with neurologic events were more often African American (43.6% vs 28.6%, P < .001) with prior history of CVA (24.5% vs 7.8%, P < .001), chronic renal insufficiency (26.6% vs 15.2%, P < .001), and insulin-dependent diabetes (19.1% vs 12.4%, P = .03). Acute myocardial infarction (56% vs 30.4%, P < .001) and cardiogenic shock (20.2% vs 3%, P < .001) were also more common among patients with neurologic events post-PCI. After multivariable adjustment, use of an intraaortic balloon pump was strongly associated with neurologic events (odds ratio [OR] 4.9, 95% CI 2.7-8.8, P < .001), as was prior CVA (OR 2.4, 95% CI 1.4-4.4, P = .002) and African American race (OR 2.4, 95% CI 1.5-3.9, P < .001); there was a borderline association with the use of a thrombus extraction device (OR 1.7, 95% CI 0.9-3.2, P = .09). In-hospital mortality (20.0% vs 1.5%, P < .001) and 1-year mortality (45.0% vs 7.3%, P < .001) were also much higher in patients with neurologic events. CONCLUSION: Neurologic events post-PCI are associated with markedly worse in-hospital outcomes. The incidence of CVA and TIA post-PCI, however, remained stable over the last 12 years despite an increase in risk factors for CVA. PMID- 26856220 TI - Aggressive hydraTion in patients with ST-Elevation Myocardial infarction undergoing Primary percutaneous coronary intervention to prevenT contrast-induced nephropathy (ATTEMPT): Study design and protocol for the randomized, controlled trial, the ATTEMPT, RESCIND 1 (First study for REduction of contraSt-induCed nephropathy followINg carDiac catheterization) trial. AB - Adequate hydration is recommended for acute ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) to prevent contrast-induced nephropathy (CIN). However, the optimal hydration regimen has not been well established in these high-risk patients. The objective of this study is to evaluate the efficacy of a preprocedural loading dose plus postprocedural aggressive hydration with normal saline guided by the left ventricular end-diastolic pressure (LVEDP) compared with general hydration for CIN prevention. The ATTEMPT study is a multicenter, open-label, investigator driven, randomized controlled trial in China. Approximately 560 patients with STEMI undergoing primary PCI will be randomized (1:1) to receive either periprocedural general hydration (control group) or aggressive hydration (treatment group). Patients in the control group receive periprocedural general hydration with <=500 mL normal saline (within 6 hours) at a normal rate (0.5 or 1 mL/kg . h). Patients in the treatment group receive a preprocedural loading dose (125/250 mL) of normal saline within 30 minutes and intravenous hydration at a normal rate until LVEDP is available, followed by postprocedural aggressive hydration guided by LVEDP for 4 hours and then continuous intravascular hydration at the normal rate until 24 hours after PCI. The primary end point is CIN, defined as a >25% or 0.5-mg/dL increase in serum creatinine from baseline during the first 48 to 72 hours after procedure. The ATTEMPT study has the potential to identify optimal hydration regimens for STEMI patients undergoing PCI. PMID- 26856221 TI - Design and rationale of the HITTS randomized controlled trial: Effect of High intensity Interval Training in de novo Heart Transplant Recipients in Scandinavia. AB - There is no consensus on how, when, and at what intensity exercise should be performed and organized after heart transplantation (HTx). Most rehabilitation programs are conducted in HTx centers, which might be impractical and costly. We have recently shown that high-intensity interval training (HIT) is safe, well tolerated, and efficacious in maintenance HTx recipients, but there are no studies among de novo patients, and whether HIT is feasible and superior to moderate training in HTx recipients is unclear. A total of 120 clinically stable HTx recipients older than 18 years will be recruited from 3 Scandinavian HTx centers. Participants are randomized to HIT or moderate training, shortly after surgery. All exercises are supervised in the patients' local communities. Testing at baseline and follow-up includes the following: VO2peak (primary end point), muscle strength, body composition, quality of life, myocardial performance, endothelial function, biomarkers, and progression of cardiac allograft vasculopathy. A subgroup (n = 90) will also be tested at 3-year follow-up to assess long-term effects of exercise. So far, the HIT intervention is well tolerated, without any serious adverse events. We aim to test whether decentralized HIT is feasible, safe, and superior to moderate training, and whether it will lead to significant improvement in exercise capacity and less long-term complications. PMID- 26856222 TI - Adjunctive anticoagulation during peripheral vascular intervention. AB - Endovascular techniques for the treatment of peripheral arterial disease are becoming an increasingly common alternative to open surgery, yet the degree of anticoagulation and choice of anticoagulant to optimize outcomes in these procedures remain uncertain. To date, few randomized trials have directly compared different anticoagulants for use during peripheral vascular interventions. It is also unclear if the approach to anticoagulation should be individualized to each vascular bed or if common principles are shared among them. This has led practitioners across different specialties to use a variety of different methods for anticoagulation, with most extrapolated from techniques used in percutaneous coronary interventions. In this review, we analyze the current literature for anticoagulation used during peripheral vascular intervention of the lower extremity, renal, carotid, and aortic arteries, with special consideration to the choice of anticoagulant used to maximize safe and effective procedural outcomes. PMID- 26856224 TI - Thrombus aspiration in patients with large anterior myocardial infarction: A Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial substudy. AB - BACKGROUND: The TASTE trial did not demonstrate clinical benefit of thrombus aspiration (TA). High-risk patients might benefit from TA. METHODS: The TASTE trial was a multicenter, randomized, controlled, open-label trial obtaining end points from national registries. Patients (n = 7,244) with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) were randomly assigned 1:1 to TA and PCI or to PCI alone. We assessed the 1-year clinical effect of TA in a subgroup with potentially large anterior STEMI: mid or proximal left anterior descending coronary artery infarct lesion, thrombolysis in myocardial infarction 0 to 2 flow, and symptom onset to PCI time <=5 hours. In this substudy, patient eligibility criteria corresponded to that of the INFUSE AMI study. RESULTS: In total, 1,826 patients fulfilled inclusion criteria. All cause mortality at 1 year of patients randomized to TA did not differ from those randomized to PCI only (hazard ratio [HR] 1.05, 95% CI 0.74-1.49, P = .77). Rates of rehospitalization for myocardial infarction, heart failure, and stent thrombosis did not differ between groups (HR 0.87, 95% CI 0.51-1.46, P = .59; HR 1.10 95% CI 0.77-1.58, P = .58; and HR 0.75, 95% CI 0.30-1.86, P = .53, respectively). This was also the case for the combined end point of all-cause mortality and rehospitalization for myocardial infarction, heart failure, or stent thrombosis (HR 1.00, 95% CI 0.79-1.26, P = .99). CONCLUSION: In patients with STEMI and large area of myocardium at risk, TA did not affect outcome within 1 year. PMID- 26856223 TI - Utility of the Framingham Risk Score in predicting secondary events in patients following percutaneous coronary intervention: A time-trend analysis. AB - BACKGROUND: The Framingham Risk Score (FRS) effectively predicts the risk of cardiovascular events in the primary prevention setting. However, its use in identifying the risk of cardiovascular events among patients with established coronary heart disease is unknown. This study aimed to evaluate the utility of the FRS in predicting long-term secondary events in patients following percutaneous coronary intervention (PCI) across a 17-year period. METHODS: Consecutive patients (N=25,519, male=71%, mean age=66.5+/-12.1years) undergoing PCI at Mayo Clinic between January 1, 1994, and December 31, 2010, were screened for cardiovascular risk factors to determine their FRS at baseline (mean score 7.0+/-3.3). Patients were divided into 4 groups according to their FRS 10-year predicted risk of cardiovascular disease (CVD) and were followed up for a median duration of 109months (Q1-Q3, 63-155) for the primary composite end point of cardiac death and myocardial infarction (MI) and the secondary end points of all cause death, noncardiac death, and revascularization (surgical and percutaneous). Patients were separately divided into 5 equal temporal subsets depending on the date of PCI and were fit to a Cox model with an interaction between the FRS 10 year predicted risk and time. RESULTS: The FRS was significantly associated with the 10-year actual risk of cardiac death and MI (both combined and separately, P<.001 respectively), noncardiac death (P<.001), all-cause death (P<.001), and revascularization (P=.018). However, the FRS discriminated risk poorly for all end points (C-statistic: cardiac death and MI, 56.8; all-cause death, 58.7; noncardiac death, 51.8; and revascularization, 51.3) even among patients presenting with acute coronary syndrome or stable angina. Over the 17-year period of time, the association between the FRS 10-year predicted risk and the 10-year actual risk of events did not change (P=.72). CONCLUSIONS: The FRS discriminates the risk of long-term secondary events, including cardiac death, MI, and revascularization, in patients following PCI poorly, even among those presenting with acute coronary syndrome. The current study supports the development of novel secondary prevention risk models. PMID- 26856225 TI - Reducing cardiovascular risk through treatment of obstructive sleep apnea: 2 methodological approaches. AB - Obstructive sleep apnea (OSA) significantly impacts cardiovascular health, demonstrated by observational investigations showing an independently increased risk of ischemic heart disease, diabetes, hypertension, congestive heart failure, acute coronary syndrome, stroke, cardiovascular mortality, and all-cause mortality. Positive airway pressure (PAP), a medical therapy for sleep apnea, reverses airway obstruction and may help reduce cardiovascular risk. Prior to planning large phase III randomized controlled trials to test the impact of PAP on cardiovascular outcomes, several gaps in knowledge need to be addressed. This article describes 2 independent studies that worked collaboratively to fill these gaps. The populations, design features, and relative benefits/challenges of the 2 studies (SleepTight and BestAIR) are described. Both studies were encouraged to have multidisciplinary teams with expertise in behavioral interventions to improve PAP compliance. Both studies provide key information that will be useful to the research community in future large-scale, event-driven, randomized trials to evaluate the efficacy and/or effectiveness of strategies to identify and treat significant OSA for decreasing risk of major adverse cardiovascular events in high-risk patients. PMID- 26856227 TI - Novel mechanisms for cerebral blood flow regulation in patients with congenital heart disease. AB - BACKGROUND: The mechanisms that regulate cerebral flow in patients after surgery for congenital heart diseases (CHDs) remain poorly understood. We tested our hypothesis that postoperative patients with CHD have disease- or hemodynamic specific compensatory mechanisms for maintaining cerebral perfusion. METHODS: A total of 89 children with specific hemodynamics including Glenn (n = 14), Fontan (n = 19), repaired tetralogy of Fallot (n = 24), and control patients (n = 32) were enrolled. The resistance and blood flow distribution between the brain (Rc and CIc) and lower body (Rs and CIs) were calculated by measuring the hemodynamic changes resulting from inferior vena cava occlusion during cardiac catheterization. RESULTS: Despite considerable differences in cardiac index and superior vena cava pressure (SVCp), cerebral blood flow was preserved in all noncontrol groups, with a ratio between the vascular resistances in the cerebral and lower body circulation (Rc/Rs) that was significantly lower than that in controls. Interestingly, the reduced Rc/Rs of Glenn patients was mediated by the reduced Rc, whereas augmented Rs was conducive to the reduced Rc/Rs in the Fontan and tetralogy of Fallot groups. Multivariate analysis revealed that high SVCp was significantly associated with low Rc. Although low cardiac index was significantly associated with increased Rc and Rs, its impact was much greater on Rs than on Rc. CONCLUSIONS: Compensatory mechanisms for cerebral flow regulation occur according to hemodynamic abnormality type in postoperative patients with CHD. Because such a regulation mechanism implies cerebral circulation fragility, further investigations are needed to address the impacts of cerebral circulation properties on neurodevelopmental outcomes. PMID- 26856226 TI - Edoxaban vs warfarin in patients with nonvalvular atrial fibrillation in the US Food and Drug Administration approval population: An analysis from the Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial. AB - BACKGROUND: Edoxaban is a specific anti-Xa inhibitor that, in comparison to warfarin, has been found to be noninferior for the prevention of stroke or systemic embolism (SSE) and to reduce bleeding significantly in patients with nonvalvular atrial fibrillation (AF). The US Food and Drug Administration (FDA) approved the higher-dose edoxaban regimen (60/30 mg) in patients with AF and a creatinine clearance of <=95 mL/min. We report for the first time the clinical characteristics, efficacy, and safety of the FDA-approved population in the ENGAGE AF--TIMI 48 trial. METHODS: The patients included had been treated with either warfarin or edoxaban 60/30 mg and had a creatinine clearance of <=95 mL/min. The primary efficacy was SSE, and the principal safety end point was major bleeding (International Society on Thrombosis and Haemostasis classification). Median follow-up was 2.8 years. RESULTS: Patients in the FDA approved cohort were older, were more likely female, and had higher CHADS2 and HAS-BLED scores, as compared with patients not included in the FDA label. The primary end point occurred in 1.63%/y with edoxaban vs 2.02%/y with warfarin (hazard ratio [HR] 0.81, 95% CI 0.67-0.97, P = .023). Edoxaban significantly reduced the rate of hemorrhagic stroke (HR 0.47, 95% CI 0.31-0.72, P < .001) and cardiovascular death (HR 0.84, 95% CI 0.73-0.97, P = .015). Ischemic stroke rates were similar between the treatment groups (1.31%/y vs 1.39%/y, P = .97). Major bleeding was significantly lower with edoxaban (3.16%/y vs 3.77%/y; HR 0.84, 95% CI 0.72-0.98, P = .023). CONCLUSION: In the FDA-approved cohort of the ENGAGE AF- TIMI 48 trial, treatment with edoxaban 60/30 mg was superior to warfarin in the prevention of SSE and significantly reduced cardiovascular death and bleeding, especially fatal bleeding and hemorrhagic stroke. PMID- 26856228 TI - Multivessel versus culprit lesion only percutaneous revascularization plus potential staged revascularization in patients with acute myocardial infarction complicated by cardiogenic shock: Design and rationale of CULPRIT-SHOCK trial. AB - BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock (CS), up to 80% of patients present with multivessel coronary artery disease. Currently, the best revascularization strategy is unknown. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The CULPRIT-SHOCK study is a 706-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare culprit lesion only percutaneous coronary intervention (PCI) with possible staged non culprit lesion revascularization versus immediate multivessel PCI in patients with CS complicating acute myocardial infarction. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of CULPRIT-SHOCK is 30-day mortality and severe renal failure requiring renal replacement therapy. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, an intermediate- and long-term follow-up at 6 and 12 months will be performed. Safety endpoints include the assessment of bleeding and stroke. CONCLUSIONS: The CULPRIT-SHOCK trial will address the question of optimal revascularization strategy in patients with multivessel disease and acute myocardial infarction complicated by CS. PMID- 26856229 TI - Untangling the paradox: Obesity as prognostic marker in prevalent cardiovascular disease. PMID- 26856231 TI - Automatic external defibrillator-only resuscitation in cardiac arrest? The approach may be shocking! PMID- 26856230 TI - Excess weight and life expectancy after acute myocardial infarction: The obesity paradox reexamined. AB - BACKGROUND: An "obesity paradox" has been described in patients with acute myocardial infarction (AMI), whereby obese and overweight patients have a lower risk of short-term mortality after AMI than normal-weight patients. However, the long-term association of obesity with mortality after AMI remains unknown. METHODS: We used data from the Cooperative Cardiovascular Project, a prospective medical record study of Medicare beneficiaries hospitalized with AMI with 17 years of follow-up (N = 124,981), to evaluate the association of higher body mass index (BMI) with short- and long-term survival after AMI. Cox proportional hazards models were used to estimate life expectancy after AMI and the years of potential life lost or gained attributable to excess weight. RESULTS: Approximately 41.5% of patients were classified as normal weight; 38.7%, as overweight; 14.3%, as obese; and 5.5%, as morbidly obese. Normal-weight patients had the highest crude mortality at all follow-up time points, whereas obese patients had the lowest. Adjustment for patient and treatment characteristics reduced this difference, but the survival benefit persisted in overweight and obese patients at all time points. Morbidly obese and normal-weight patients had a comparable risk of death at 17 years. Life expectancy estimates were generally lowest for morbidly obese patients and highest for overweight patients. Differences in life expectancy between BMI groups were most pronounced in younger patients. After adjustment, overweight and obesity were associated with greater life years at all ages; however, morbid obesity was only associated with better survival in patients >=75 years of age at the time of AMI. CONCLUSIONS: Overweight and obesity are associated with improved short- and long-term survival after AMI, which results in moderate gains in life expectancy relative to normal weight patients. These findings suggest that higher BMI confers a protective advantage over the entire remaining lifespan in older patients with AMI. PMID- 26856232 TI - Employment and residential characteristics in relation to automated external defibrillator locations. AB - BACKGROUND: Survival from out-of-hospital cardiac arrest (OHCA) is generally poor and varies by geography. Variability in automated external defibrillator (AED) locations may be a contributing factor. To inform optimal placement of AEDs, we investigated AED access in a major US city relative to demographic and employment characteristics. METHODS AND RESULTS: This was a retrospective analysis of a Philadelphia AED registry (2,559 total AEDs). The 2010 US Census and the Local Employment Dynamics database by ZIP code was used. Automated external defibrillator access was calculated as the weighted areal percentage of each ZIP code covered by a 400-m radius around each AED. Of 47 ZIP codes, only 9% (4) were high-AED-service areas. In 26% (12) of ZIP codes, less than 35% of the area was covered by AED service areas. Higher-AED-access ZIP codes were more likely to have a moderately populated residential area (P = .032), higher median household income (P = .006), and higher paying jobs (P =. 008). CONCLUSIONS: The locations of AEDs vary across specific ZIP codes; select residential and employment characteristics explain some variation. Further work on evaluating OHCA locations, AED use and availability, and OHCA outcomes could inform AED placement policies. Optimizing the placement of AEDs through this work may help to increase survival. PMID- 26856233 TI - Community-based automated external defibrillator only resuscitation for out-of hospital cardiac arrest patients. AB - BACKGROUND: Speed is the cornerstone of rescue for out-of-hospital cardiac arrest. As a consequence, community participation programs have been initiated to decrease response times. Even in the very best of these programs, however, short term survival rates hover around 10% and long-term survival rates are half that. In most locales, survival is far worse. In Piacenza, Italy, responders have been trained for more than a decade to use publicly available automated external defibrillators (AEDs) and eschew the performance of cardiopulmonary resuscitation (CPR). It is known locally as "Progetto Vita." METHODS: From 2001 to 2014, we prospectively collected outcome data on all Progetto Vita-treated patients and all 3271 standard emergency medical services (EMS) patients. Progetto Vita rescuers simply accessed a public AED, turned it on, and only followed its instructions. Progetto Vita rescuers did not do CPR of any sort. If EMS arrived prior to initiation or even completion of the Progetto Vita protocol, EMS supplanted Progetto Vita efforts and patients were not included in the Progetto Vita cohort. Follow-up was collected by each responder's data files, medical record review, and use of the Italian system death index. All cardiac arrest patients' death status was validated in 100% of patients through August 1, 2014. FINDINGS: Survival to hospital discharge occurred in 39 (41.4%) of the 95 patients treated by Progetto Vita and in 193 (5.9%) of the 3271 EMS patients. At 13-year follow-up, the Kaplan-Meier estimates of survival were 31.8% when AEDs only were used and 2.4% for standard EMS/CPR response. Estimates of survival are significantly better for Progetto Vita AED-only therapy when survival was stratified by time to respond, gender, location of cardiac arrest, and shockable rhythm. Relative to the 95 EMS patients with the fastest response times, Progetto Vita intervention was associated with a more than 2-fold increased rate of survival. INTERPRETATION: This is the first demonstration of excellent long-term survival from out-of-hospital cardiac arrest by promoting speed and ease of lay AED response without CPR. PMID- 26856234 TI - Associations of breast-feeding patterns and introduction of solid foods with childhood bone mass: The Generation R Study. AB - Breast-feeding has been associated with later bone health, but results from previous studies are inconsistent. We examined the associations of breast-feeding patterns and timing of introduction of solids with bone mass at the age of 6 years in a prospective cohort study among 4919 children. We collected information about duration and exclusiveness of breast-feeding and timing of introduction of any solids with postnatal questionnaires. A total body dual-energy X-ray absorptiometry scan was performed at 6 years of age, and bone mineral density (BMD), bone mineral content (BMC), area-adjusted BMC (aBMC) and bone area (BA) were analysed. Compared with children who were ever breast-fed, those never breast-fed had lower BMD (-4.62 mg/cm2; 95 % CI -8.28, -0.97), BMC (-8.08 g; 95 % CI -12.45, -3.71) and BA (-7.03 cm2; 95 % CI -12.55, -1.52) at 6 years of age. Among all breast-fed children, those who were breast-fed non-exclusively in the first 4 months had higher BMD (2.91 mg/cm2; 95 % CI 0.41, 5.41) and aBMC (3.97 g; 95 % CI 1.30, 6.64) and lower BA (-4.45 cm2; 95 % CI -8.28, -0.61) compared with children breast-fed exclusively for at least 4 months. Compared with introduction of solids between 4 and 5 months, introduction <4 months was associated with higher BMD and aBMC, whereas introduction between 5 and 6 months was associated with lower aBMC and higher BA. Additional adjustment for infant vitamin D supplementation did not change the results. In conclusion, results from the present study suggest that ever breast-feeding compared with never breast-feeding is associated with higher bone mass in 6-year-old children, but exclusive breast feeding for 4 months or longer was not positively associated with bone outcomes. PMID- 26856235 TI - Printing Technologies for Medical Applications. AB - Over the past 15 years, printers have been increasingly utilized for biomedical applications in various areas of medicine and tissue engineering. This review discusses the current and future applications of 3D bioprinting. Several 3D printing tools with broad applications from surgical planning to 3D models are being created, such as liver replicas and intermediate splints. Numerous researchers are exploring this technique to pattern cells or fabricate several different tissues and organs, such as blood vessels or cardiac patches. Current investigations in bioprinting applications are yielding further advances. As one of the fastest areas of industry expansion, 3D additive manufacturing will change techniques across biomedical applications, from research and testing models to surgical planning, device manufacturing, and tissue or organ replacement. PMID- 26856236 TI - Oncometabolite Tinkers with Genome Folding, Boosting Oncogene Expression. AB - A recent article makes a compelling case for a new mechanism by which heterozygous mutations in isocitrate dehydrogenases (IDH1/2)--implicated in cancer--undermine gene regulation. 2-Hydroxyglutarate (2HG) produced by mutant IDH alters the binding of the chromosomal organizer protein CTCF, disrupting the spatial and regulatory organization of the genome. PMID- 26856237 TI - Exon Snipping in Duchenne Muscular Dystrophy. AB - Duchenne muscular dystrophy (DMD) is a life-limiting neuromuscular disorder caused by mutations in the DMD gene encoding dystrophin. We discuss very recent studies that used CRISPR/Cas9 technology to 'snip out' mutated exons in DMD, restoring the reading frame of the gene. We also present cautionary aspects of translating this exciting technology into clinical practice. PMID- 26856239 TI - Porcelain-titanium bonding with a newly introduced, commercially available system. AB - STATEMENT OF PROBLEM: Titanium is widely used in implant dentistry because of its high strength, toughness, biocompatibility, and low cost. The fabrication of complex substructures is now possible with a number of automated systems. One major obstacle to broad clinical acceptance of porcelain-titanium prostheses is the poor ceramic-metal bonding. PURPOSE: The purpose of this study was to compare titanium bonding with a traditional bonder and a newly introduced titanium bonding system. Bonding was characterized by the delamination crack initiation stress per ISO 9693:2009. MATERIAL AND METHODS: Grade 4 titanium strips were laser machined to meet ISO 9693:2009 standards. Bonding and firing of opaque porcelain was accomplished by using a traditional titanium ceramic system and a newly introduced bonding system. Variables tested besides the bonding system included the length of the porcelain block (7 mm, 8 mm, 9 mm); the thickness of the block (1.0 mm, 1.6 mm); testing the specimens 1 mm off-center; and reusing the strips. Crack initiation stresses were calculated and compared by ANOVA and the Duncan test (alpha=.05). RESULTS: The newly introduced commercially available system gave the strongest bond (41.82 +/-5.7 MPa), followed by the 9 mm specimens (32.2 +/-3.9 MPa), then a statistically similar group of the 8 mm, 7 mm, and 1.6 mm thick specimens with new Ti (approximately 23 MPa), and last a similar group with 7 mm, 8 mm, and 1 mm offset loading on reused Ti (approximately 16 MPa). The lower limit under ISO 9693:2009 was 23 MPa. CONCLUSIONS: The newly introduced commercially available system achieved much higher bond strengths than traditional titanium systems, even better than those for many high-gold alloys. PMID- 26856238 TI - Comparative phylogenetic analysis and transcriptional profiling of MADS-box gene family identified DAM and FLC-like genes in apple (Malusx domestica). AB - The MADS-box transcription factors play essential roles in various processes of plant growth and development. In the present study, phylogenetic analysis of 142 apple MADS-box proteins with that of other dicotyledonous species identified six putative Dormancy-Associated MADS-box (DAM) and four putative Flowering Locus C like (FLC-like) proteins. In order to study the expression of apple MADS-box genes, RNA-seq analysis of 3 apical and 5 spur bud stages during dormancy, 6 flower stages and 7 fruit development stages was performed. The dramatic reduction in expression of two MdDAMs, MdMADS063 and MdMADS125 and two MdFLC-like genes, MdMADS135 and MdMADS136 during dormancy release suggests their role as flowering-repressors in apple. Apple orthologs of Arabidopsis genes, FLOWERING LOCUS T, FRIGIDA, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 and LEAFY exhibit similar expression patterns as reported in Arabidopsis, suggesting functional conservation in floral signal integration and meristem determination pathways. Gene ontology enrichment analysis of predicted targets of DAM revealed their involvement in regulation of reproductive processes and meristematic activities, indicating functional conservation of SVP orthologs (DAM) in apple. This study provides valuable insights into the functions of MADS-box proteins during apple phenology, which may help in devising strategies to improve important traits in apple. PMID- 26856240 TI - High rate of missed HIV infections in individuals with indeterminate or negative HIV western blots based on current HIV testing algorithm in China. AB - It remains unclear if China's current HIV antibody testing algorithm misses a substantial number of HIV infected individuals. Of 196 specimens with indeterminate or negative results on HIV western blot (WB) retrospectively examined by HIV-1 nucleic acid test (NAT), 67.57% (75/111) of indeterminate WB samples, and 16.47% (14/85) of negative WB samples were identified as NAT positive. HIV-1 loads in negative WB samples were significantly higher than those in indeterminate WB samples. Notably, 86.67% (13/15) of samples with negative WB and double positive immunoassay results were NAT positive. The rate of HIV-1 infections missed by China's current HIV testing algorithm is unacceptably high. Thus, China should consider using NAT or integrating fourth generation ELISA into current only antibodies-based HIV confirmation. J. Med. Virol. 88:1462-1466, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26856241 TI - Sorting nexin 10 acting as a novel regulator of macrophage polarization mediates inflammatory response in experimental mouse colitis. AB - In response to changes in microenvironment, macrophages polarize into functionally distinct phenotypes, playing a crucial role in the pathogenesis of inflammatory bowel disease (IBD). Here, we investigated the effects of sorting nexin 10 (SNX10), a protein involved in endosomal trafficking and osteoclast maturation, on regulation of macrophage polarization and progression of mouse colitis. Our results revealed that SNX10 deficiency increased the population of M2-type monocytes/macrophages, and protected against colonic inflammation and pathological damage induced by dextran sulfate sodium (DSS). By in vitro study, we showed that deficiency of SNX10 polarized macrophages derived from mouse bone marrow or human peripheral blood mononuclear cells (PBMCs) towards an anti inflammatory M2 phenotype, which partially reversed by SNX10 plasmid transfection. Adoptive transfer of SNX10(-/-) macrophages ameliorated colitis in WT mice. However, transfer of WT macrophages exacerbated colitis in SNX10(-/-) mice. Our data disclose a crucial role and novel function for SNX10 in macrophage polarization. Loss of SNX10 function may be a potential promising therapeutic strategy for IBD. PMID- 26856242 TI - [Disc-fovea angle adjustment for peripallary retinal nerve fiber layer analysis by a spectral domain optical coherence tomography. Preliminary study]. AB - INTRODUCTION: Circumpapillary retinal nerve fiber layer (cpRNFL) analysis by spectral domain optical coherence tomography (SD-OCT) has become essential for the assessment of glaucoma patients. The foveal projection is conventionally below the disc plane, creating an angle with the horizontal meridian, the disc fovea angle. The purpose of this study is to evaluate the role of adjustment of cpRNFL analysis based on this angle. MATERIALS AND METHODS: This study concerns 40 control eyes and 55 eyes affected with and followed for primary open angle glaucoma (POAG). After precise localization of the optic disc center and the axis connecting it to the center of the fovea, a circular peripapillary scan is performed with Spectralis OCT (Heidelberg Engineering, Germany). The mean thickness in each of six papillary sectors and the global mean thickness of the cpRNFL were evaluated. The ROC (receiver operating characteristic) analysis evaluated the diagnostic capabilities of the various sectors before and after adjustment of the analysis for the disc-fovea angle. RESULTS: The disc-fovea angle was not different between the two groups (-7.0 +/- 1.2 degrees for controls vs. -6.6 +/- 1.2 degrees for POAG, P=0.70). There is a significant variance of this angle in both groups (the angle varies in the control group between -22.5 degrees to +1.8 degrees and in the POAG group between -18 degrees to +2.4 degrees ). The global mean and inferior temporal (IT) thickness of the cpRNFL show the best diagnostic performance. Adjustment for disc-fovea angle does not increase the diagnostic accuracy of the various sectors analyzed. Although there is an increase in the area under the curve for the IT sector after adjustment, it is not statistically significant (0.910 +/- 0.056 vs. 0.936 +/- 0.045, P=0.06). CONCLUSIONS: There is a significant variation in disc-fovea angle. In this study, accounting for it does not significantly improve the diagnostic capabilities of cpRNFL in patients with POAG. PMID- 26856243 TI - Variations in Resource Intensity and Cost Among High Users of the Emergency Department. AB - OBJECTIVES: High users of emergency department (ED) services are often identified by number of visits per year, with little exploration of the distribution/pattern of visits over time. The purpose of this study was to examine patient- and encounter-level factors and costs related to periods of short-term resource intensity among high users of the ED within a tertiary care teaching facility. METHODS: We identified all adults with at least three visits to the Ottawa Hospital ED within a 1-year period from April 1, 2012, to March 31, 2013. Within this high-user cohort, we then measured intensity of use by calculating average daily visit rates to identify individuals with a cluster of ED visits. Those with at least three ED visits/7 days at any point during follow-up were considered patients with clustered ED use (i.e., a period of short-term resource intensity). Detailed clinical and administrative data were used to compare patient- and encounter-level characteristics and cost profiles between the clustered and nonclustered groups. Analyses were repeated using varying cut points to define high users (at least five and at least eight visits per year). RESULTS: Of the 16,153 patients identified as high ED users during the study period, 13.5% had their visits clustered within a short period of time. These clustered users were more likely to be homeless, to require psychiatric services, and to leave without being seen by a physician and less likely to be admitted to the hospital. Approximately one in three (31.2%) high ED users with clustered visits returned for the same medical problem (namely pain-related disorders, shortness of breath, and cellulitis) within a 1-week period. Similar trends were observed when the high-user cohort was restricted to those with at least five and at least eight ED visits/year. Finally, patients with short-term intensity periods had lower direct and indirect costs per encounter than those without. CONCLUSIONS: Using a novel methodology that accounts for both number and intensity of ED encounters over time, we were able to identify specific subpopulations of high ED users. Further work is required to determine if this methodology has utility for targeting care pathways within this heterogeneous and high-risk patient group. PMID- 26856244 TI - Viral infection of the marine alga Emiliania huxleyi triggers lipidome remodeling and induces the production of highly saturated triacylglycerol. AB - Viruses that infect marine photosynthetic microorganisms are major ecological and evolutionary drivers of microbial food webs, estimated to turn over more than a quarter of the total photosynthetically fixed carbon. Viral infection of the bloom-forming microalga Emiliania huxleyi induces the rapid remodeling of host primary metabolism, targeted towards fatty acid metabolism. We applied a liquid chromatography-mass spectrometry (LC-MS)-based lipidomics approach combined with imaging flow cytometry and gene expression profiling to explore the impact of viral-induced metabolic reprogramming on lipid composition. Lytic viral infection led to remodeling of the cellular lipidome, by predominantly inducing the biosynthesis of highly saturated triacylglycerols (TAGs), coupled with a significant accumulation of neutral lipids within lipid droplets. Furthermore, TAGs were found to be a major component (77%) of the lipidome of isolated virions. Interestingly, viral-induced TAGs were significantly more saturated than TAGs produced under nitrogen starvation. This study highlights TAGs as major products of the viral-induced metabolic reprogramming during the host-virus interaction and indicates a selective mode of membrane recruitment during viral assembly, possibly by budding of the virus from specialized subcellular compartments. These findings provide novel insights into the role of viruses infecting microalgae in regulating metabolism and energy transfer in the marine environment and suggest their possible biotechnological application in biofuel production. PMID- 26856245 TI - Differential effect of mode of conception and infertility treatment on fetal growth and prematurity. AB - Objectives To examine perinatal outcomes in pregnancies conceived by different methods: fertile women with spontaneous pregnancies, infertile women who achieved pregnancy without treatment, pregnancies achieved by ovulation induction (OI) and in vitro fertilization or intra-cytoplasmic sperm injection (IVF/ICSI). Methods Retrospective single-center cohort study including 200 fertile and 748 infertile women stratified according to infertility treatment. The outcome measurements were preterm delivery (PTD), small-for-gestational-age (SGA), gestational diabetes, placenta previa or preeclampsia. Results The overall rate of pregnancy complications was significantly increased in all infertility groups regardless of the infertility treatment (adjusted odds ratio (OR): infertile without treatment 2.3 versus OI 2.2 versus IVF/ICSI 3.4). While PTD was mainly associated to IVF/ICSI (adjusted OR: infertile without treatment 1.3 versus OI 1.6 versus IVF/ICSI 3.3), SGA was significantly associated to both OI and IVF/ICSI (adjusted OR: infertile without treatment 1.9 versus OI 2.7 versus IVF/ICSI 2.6). All these associations remained statistically significant after adjusting by maternal age and twin pregnancy. Conclusions This study confirms the higher prevalence of pregnancy complications in infertile women irrespectively of receiving infertility treatment or not, and further describes a preferential association of prematurity with IVF/ICSI, and SGA with treated infertility (OI and IVF/ICSI). PMID- 26856246 TI - Impact of Safety-Engineered Devices on the Incidence of Occupational Blood and Body Fluid Exposures Among Healthcare Personnel in an Academic Facility, 2000 2014. AB - BACKGROUND: Legislative actions and advanced technologies, particularly dissemination of safety-engineered devices, have aided in protecting healthcare personnel from occupational blood and body fluid exposures (BBFE). OBJECTIVE: To investigate the trends in BBFE among healthcare personnel over 15 years and the impact of safety-engineered devices on the incidence of percutaneous injuries as well as features of injuries associated with these devices. METHODS: Retrospective cohort study at University of North Carolina Hospitals, a tertiary care academic facility. Data on BBFE in healthcare personnel were extracted from Occupational Health Service records (2000-2014). Exposures associated with safety engineered and conventional devices were compared. Generalized linear models were applied to measure the annual incidence rate difference by exposure type over time. RESULTS: A total of 4,300 BBFE, including 3,318 percutaneous injuries (77%), were reported. The incidence rate for overall BBFE was significantly reduced during 2000-2014 (incidence rate difference, 1.72; P=.0003). The incidence rate for percutaneous injuries was also dramatically reduced during 2001-2006 (incidence rate difference, 1.37; P=.0079) but was less changed during 2006-2014. Percutaneous injuries associated with safety-engineered devices accounted for 27% of all BBFE. BBFE was most commonly due to injecting through skin, placing intravenous catheters, and blood drawing. CONCLUSIONS: Our study revealed significant overall reduction in BBFE and percutaneous injuries likely due in part to the impact of safety-engineered devices but also identified that a considerable proportion of percutaneous injuries is now associated with these devices. Additional prevention strategies are needed to further reduce percutaneous injuries and improve design of safety-engineered devices. PMID- 26856247 TI - A genetic factor associated with low final bone mineral density in children after a long-term glucocorticoids treatment. AB - Treatment with glucocorticoids is associated with lower bone mineral density (BMD). We performed a genome-wide association study to analyze interactive effects between genotypes and cumulative dose of prednisone (PD) over 4.3 years of follow-up period on the final BMD Z-scores in 461 white children from the Childhood Asthma Management Program. No variants met the conventional criteria for genome-wide significance, and thus we looked for evidence of replication. The top 100-ranked single-nucleotide polymorphisms (SNPs) were then carried forward replication in 59 children with acute lymphoblastic leukemia (ALL) exposed to large fixed doses of PD as part of their chemotherapeutic regimen. Among them, rs6461639 (interaction P=1.88 * 10-5 in the CAMP population) showed a significant association with the final BMD Z-scores in the ALL population (P=0.016). The association of the ALL population was only present after correction for the anti metabolite treatment arm (high vs low dose). We have identified a novel SNP, rs6461639, showing a significant effect on the final BMD Z-scores in two independent pediatric populations after long-term high-dose PD treatment. PMID- 26856249 TI - A longitudinal study of the association between the GNB3 C825T polymorphism and metabolic disturbance in bipolar II patients treated with valproate. AB - This longitudinal study aimed to investigate the associations between the polymorphisms of guanine nucleotide-binding protein subunit beta-3 (GNB3) C825T and metabolic disturbance in bipolar II disorder (BP-II) patients being treated with valproate (VPA). A 100 BP-II patients received a 12-week course of VPA treatment, and their body weight and metabolic indices were measured. At baseline, the GNB3 C825T polymorphisms were associated with the triglyceride level (P=0.032) in BP-II patients. During the VPA treatment course, the polymorphisms were not only associated with body mass index (BMI) and waist circumference (P-values=0.009 and 0.001, respectively), but also with total cholesterol, triglyceride, low-density lipoprotein and leptin levels (P values=0.004, 0.002, 0.031 and 0.015, respectively). Patients with the TT genotype had a lower BMI, smaller waist circumference, and lower levels of lipids and leptin than those with the CT or CC genotypes undergoing the VPA treatment course. PMID- 26856251 TI - New Findings in Adult Opsoclonus-Myoclonus Syndrome. PMID- 26856248 TI - Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines. AB - Variation in the expression level and activity of genes involved in drug disposition and action ('pharmacogenes') can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use. PMID- 26856252 TI - The program structure does not reliably recover the correct population structure when sampling is uneven: subsampling and new estimators alleviate the problem. AB - Inferences of population structure and more precisely the identification of genetically homogeneous groups of individuals are essential to the fields of ecology, evolutionary biology and conservation biology. Such population structure inferences are routinely investigated via the program structure implementing a Bayesian algorithm to identify groups of individuals at Hardy-Weinberg and linkage equilibrium. While the method is performing relatively well under various population models with even sampling between subpopulations, the robustness of the method to uneven sample size between subpopulations and/or hierarchical levels of population structure has not yet been tested despite being commonly encountered in empirical data sets. In this study, I used simulated and empirical microsatellite data sets to investigate the impact of uneven sample size between subpopulations and/or hierarchical levels of population structure on the detected population structure. The results demonstrated that uneven sampling often leads to wrong inferences on hierarchical structure and downward-biased estimates of the true number of subpopulations. Distinct subpopulations with reduced sampling tended to be merged together, while at the same time, individuals from extensively sampled subpopulations were generally split, despite belonging to the same panmictic population. Four new supervised methods to detect the number of clusters were developed and tested as part of this study and were found to outperform the existing methods using both evenly and unevenly sampled data sets. Additionally, a subsampling strategy aiming to reduce sampling unevenness between subpopulations is presented and tested. These results altogether demonstrate that when sampling evenness is accounted for, the detection of the correct population structure is greatly improved. PMID- 26856250 TI - The GRM7 gene, early response to risperidone, and schizophrenia: a genome-wide association study and a confirmatory pharmacogenetic analysis. AB - The search for biomarkers of response to antipsychotic medications is hindered by difficulties inherent in the topic or related to persistent methodological difficulties, such as high rates of anticipated discontinuation and consequent distortions in the imputation of missing data. Because early response to antipsychotics represents a sufficiently reliable index of the subsequent treatment response in patients with schizophrenia, we undertook a real-world, genome-wide association study (GWAS) with the aim of identifying genetic predictors of response to risperidone after 2 weeks in 86 patients with schizophrenia. Limited to the associations reaching significance in the GWAS, confirmatory analysis relative to risperidone response over 9 months was also designed involving 97 patients (European only) enroled in the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) genetic substudy. The GWAS revealed a significant association (false discovery rate 0.02) of the single nucleotide polymorphism rs2133450 inside the GRM7 gene with Emsley's positive domain derived from the positive and negative syndrome scale (PANSS). Patients with the rs2133450 CC genotype presented poorer improvement in the positive domain over 2 weeks, with odds ratios of 12.68 (95% CI, 3.51-45.76) and 6.95 (95% confidence interval (CI), 2.37-20.37) compared with patients with the AA and AC genotypes, respectively. Compared with A homozygotes, rs2133450 C homozygotes enroled in the CATIE-derived confirmatory analysis showed less improvement in Emsley's positive, excited and depression domains, positive and general PANSS subtypes, and total PANSS after 9 months of treatment with risperidone. The original GWAS and the CATIE-derived confirmatory analysis support the proposal that the rs2133450 may have translational relevance as a predictor of response to risperidone. PMID- 26856254 TI - Improving Risk Assessment Calculations for Traditional Foods Through Collaborative Research with First Nations Communities. AB - As industrial development is increasing near northern Canadian communities, human health risk assessments (HHRA) are conducted to assess the predicted magnitude of impacts of chemical emissions on human health. One exposure pathway assessed for First Nations communities is the consumption of traditional plants, such as muskeg tea (Labrador tea) (Ledum/Rhododendron groenlandicum) and mint (Mentha arvensis). These plants are used to make tea and are not typically consumed in their raw form. Traditional practices were used to harvest muskeg tea leaves and mint leaves by two First Nations communities in northern Alberta, Canada. Under the direction of community elders, community youth collected and dried plants to make tea. Soil, plant, and tea decoction samples were analyzed for inorganic elements using inductively coupled plasma-mass spectrometry. Concentrations of inorganic elements in the tea decoctions were orders of magnitude lower than in the vegetation (e.g., manganese 0.107 mg/L in tea, 753 mg/kg in leaves). For barium, the practice of assessing ingestion of raw vegetation would have resulted in a hazard quotient (HQ) greater than the benchmark of 0.2. Using measured tea concentrations it was determined that exposure would result in risk estimates orders of magnitude below the HQ benchmark of 0.2 (HQ = 0.0049 and 0.017 for muskeg and mint tea, respectively). An HHRA calculating exposure to tea vegetation through direct ingestion of the leaves may overestimate risk. The results emphasize that food preparation methods must be considered when conducting an HHRA. This study illustrates how collaboration between Western scientists and First Nations communities can add greater clarity to risk assessments. PMID- 26856253 TI - Management of behavioural symptoms of dementia in a specialized unit care. AB - BACKGROUND: In France, the Alzheimer Plan 2008-2012 has enabled the development of units specialized in managing the behavioural and psychological disorders found in cognitive pathologies, with an emphasis on both pharmacological and non pharmacological treatments. The aim of this study was to analyze the evolution of behavioural symptoms, autonomy, and psychotropic drug prescriptions at a cognitive and behavioural unit in Toulouse, France. METHODS: Prospective study, with systematic analyze of data for patients hospitalized in a cognitive and behavioral unit. RESULTS: This 2-year study included 199 patients. Behavioural symptoms were significantly improved during the follow-up period and remained so after discharge. Autonomy, especially in walking, was not altered. The prescription of psychotropic drugs, such as neuroleptics, was significantly lower at discharge. CONCLUSION: This study showed the effectiveness of overall care, with an emphasis on pharmacological and non-pharmacological treatments, in managing disruptive behavioural symptoms in a specialized unit. PMID- 26856255 TI - Identification of five substituted phenethylamine derivatives 5-MAPDB, 5-AEDB, MDMA methylene homolog, 6-Br-MDMA, and 5-APB-NBOMe. AB - This paper reports analytical properties of five substituted phenethylamine derivatives seized from a clandestine laboratory. These five derivatives include 5-(2-methylaminopropyl)-2,3-dihydrobenzofuran (5-MAPDB, 1), 5-(2-aminoethyl)-2,3 dihydrobenzofuran (5-AEDB, 2), N,2-dimethyl-3-(3,4-methylenedioxyphenyl)propan-1 amine (MDMA methylene homolog, 3), 6-bromo-3,4-methylenedioxymethamphetamine (6 Br-MDMA, 4), and 1-(benzofuran-5-yl)-N-(2-methoxybenzyl)propan-2-amine (5-APB NBOMe, 5). These compounds were identified by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance spectroscopy (NMR). No analytical properties about compounds 1-4 have appeared until now, making this the first report on these compounds. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26856256 TI - Lithium doped calcium phosphate cement maintains physical mechanical properties and promotes osteoblast proliferation and differentiation. AB - Calcium phosphate cement (CPC) has been widely used in bone tissue repairing due to its physical mechanical properties and biocompatibility. Addition of trace element to CPC has shown promising evidence to improve the physical properties and biological activities of CPC. Lithium (Li) has effect on osteoblast proliferation and differentiation. In this study, we incorporated Li to CPC and examined the physical properties of Li/CPC and its effect on osteoblast proliferation and differentiation. We found that Li doped CPC maintained similar setting time, pore size distribution, compressive strength, composition, and morphology as CPC without Li. Additionally, Li doped CPC improved osteoblast proliferation and differentiation significantly compared to CPC without Li. To our knowledge, our results, for the first time, show that Li doped CPC has beneficial effect on osteoblast in cell culture while keeps the excellent physical-mechanical properties of CPC. This study will lead to potential application of Li doped CPC in bone tissue engineering. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 944-952, 2017. PMID- 26856257 TI - Outcomes of intrahepatic cholangiocarcinoma with portal vein tumor thrombus following hepatic resection. AB - BACKGROUND AND AIM: Portal vein tumor thrombus (PVTT) is not commonly used in the treatment of intrahepatic cholangiocarcinoma (ICC), and its impact on the prognosis of ICC is unclear. We aimed to assess the outcomes of ICC with or without PVTT after hepatic resection. METHODS: From January 2000 to December 2005, the data from all consecutive patients with ICC who underwent hepatic resection at our hospital were retrospectively analyzed. According to the Cheng's PVTT Classification (types I-IV), we compared the survival outcomes of ICC patients (with or without PVTT) and prognosis of patients with ICC with different types of PVTT. RESULTS: Three hundred and three patients with ICC were enrolled in this study (59 with PVTT). The incidence of PVTT was 19.4% (59/303). The median survival times were 12.68 and 28.91 months for ICC patients with and without PVTT, respectively (P < 0.001). The multivariate analysis demonstrated that PVTT (hazard ratio [HR] 1.783; confidence interval 95% [1.279; 2.487]) was an independent risk factor for overall survival. Patients with type I PVTT exhibited significantly better survival than those with types II and III PVTT. CONCLUSION: The ICC patients with PVTT exhibit a poorer prognosis compared with ICC patients without PVTT after hepatic resection. PMID- 26856258 TI - Interaction between functional health literacy and telehomecare: Short-term effects from a randomized trial. AB - This study was conducted as part of a randomized, controlled trial, and explored whether the introduction of a Danish telehomecare intervention, referred to as 'the Telekit', and its associated educational components affect functional health literacy. The study sample consisted of 60 chronic obstructive pulmonary disease patients in the intervention group who received the Telekit, and 56 in the control group; all participants were collected from the large-scale, randomized TeleCare North trial by consecutive sampling. To avoid recall bias, the design did not include a baseline measurement, comparing instead the post-intervention measurements between the intervention and control groups. First, the comparability of the two groups was determined, and statistically significant differences in their functional health literacy scores were examined using an independent t-test. Furthermore, the associations between functional health literacy and both groups were tested using multiple regression analysis. No statistically significant difference was observed between the intervention and control groups, suggesting that the introduction of the Telekit and its associated educational components has no effect on functional health literacy. However, further research should be conducted using a larger sample. PMID- 26856259 TI - Synthesis of 1,3-diaryl-3-trifluoromethylcyclopropenes by transition-metal-free reaction of 2,2,2-trifluoroacetophenone tosylhydrazones with alkynes: the effect of the trifluoromethyl group. AB - 1,3-Diaryl-3-trifluoromethylcyclopropenes and 2-aryl- or 2-alkyl-1,3-diaryl-3 trifluoromethylcyclopropenes are prepared in a very simple way by reaction between 1,1,1-trifluoroacetophenone tosylhydrazones and terminal or internal alkynes, respectively, in a base promoted process that does not require the presence of any metal catalyst. The essential role of the trifluoromethyl group, which enables the formation of the cyclopropenes instead of the expected pyrazoles, has been computationally investigated, suggesting the participation of a free carbene. PMID- 26856260 TI - Leaf unfolding of Tibetan alpine meadows captures the arrival of monsoon rainfall. AB - The alpine meadow on the Tibetan Plateau is the highest and largest pasture in the world, and its formation and distribution are mainly controlled by Indian summer monsoon effects. However, little is known about how monsoon-related cues may trigger spring phenology of the vast alpine vegetation. Based on the 7-year observations with fenced and transplanted experiments across lower to upper limits of Kobresia meadows in the central plateau (4400-5200 m), we found that leaf unfolding dates of dominant sedge and grass species synchronized with monsoon onset, regardless of air temperature. We also found similar patterns in a 22-year data set from the northeast plateau. In the monsoon-related cues for leaf unfolding, the arrival of monsoon rainfall is crucial, while seasonal air temperatures are already continuously above 0 degrees C. In contrast, the early emerging cushion species generally leafed out earlier in warmer years regardless of precipitation. Our data provide evidence that leaf unfolding of dominant species in the alpine meadows senses the arrival of monsoon-season rainfall. These findings also provide a basis for interpreting the spatially variable greening responses to warming detected in the world's highest pasture, and suggest a phenological strategy for avoiding damages of pre-monsoon drought and frost to alpine plants. PMID- 26856262 TI - [Relationship of Distal Anterior Cerebral Artery Aneurysm Arising from the Supracallosal Portion and Accessory Anterior Cerebral Artery]. AB - Median artery of the corpus callosum(MACC)refers to the median artery of the triplicate anterior cerebral artery(ACA). When MACC distributes to one or to both hemispheres, it is known as the accessory ACA. We performed detailed angiographic analysis of 32 consecutive patients operated upon for distal ACA(DACA)aneurysms, and noted that all DACA aneurysms occurring in the supracallosal portion were accompanied by an accessory ACA as vascular malformation. Such relationship between accessory ACA and DACA aneurysm in the supracallosal portion has not been previously reported. PMID- 26856263 TI - [Extendable Cords to Prevent Tumbling of a Suction Device during Craniotomy]. AB - OBJECTIVE: Suction is necessary during craniotomy, and intraoperative tumbling of the suction device interrupts operative procedures. To avoid this, we developed a technique that would fasten the device to an extendable cord as is used to secure cell phones. SURGICAL TECHNIQUE: We used this technique in more than 300 craniotomies at the specific point of time when the suction device tends to tumble, i. e., during the opening and closure of a wound, which requires frequent instrument exchanges. Extendable cords fastened to the tip of the suction hose using a gift tie were attached to the drapes to secure the suction device next to the operative field. During the operation, the extendable cord followed the suction device manipulations. Consequently, although there was some tension in the cord during its extension, the maneuverability of the suction device was maintained. As the hanging suction device was closer to the operative field than devices stored in conventional pockets, its manipulation was easier and quicker. Upon release, the suction device automatically returned to its original position without distracting the surgeon. Tumbling of the device was prevented, and there were no procedure-related complications. CONCLUSIONS: Our simple modification using extendable cords prevented tumbling, avoided unnecessary replacements, and eased the manipulation of a suction device. PMID- 26856264 TI - [Multi-Layered Closure of Transorbital Penetrating Brain Injury without Bone Reconstruction: A Case Report]. AB - A 26-year-old man was injured in a motor vehicle accident. He sustained a compound orbital fracture with brain contusion. The brain tissue protruded through the orbit. Computed tomography showed a long contusion with a moderate amount of hematoma in the right frontal lobe. No foreign body was observed in the cranium. On 3D CTA, the major cerebral vessels were found to be intact. An urgent surgery was first performed by neurosurgeons and subsequently by ophthalmologists. The periosteum was left on the skull. A frontal periosteal, a right temporal fascial, and a right temporal muscular flap were prepared. After debridement and irrigation, the dural tear was closed with the right periosteal and fascial flaps. Finally, the frontal fascia was used to cover the orbital defect. The patient's clinical course was favorable. The patient was able to walk when discharged 46 days after the surgery. A penetrating brain injury through the orbit is rare, and its treatment is not established. A key to successful management of this injury is immediate assessment. Foreign bodies in the cranium, especially metal, should be checked for immediately. The cerebral vessels should also be evaluated. Usually, a surgical intervention is necessary. Since bone reconstruction can be associated with a risk of infection, a multi-layered closure, as described in this report, could prevent leakage of cerebrospinal fluid and subsequent meningitis. PMID- 26856265 TI - [Hemorrhagic Adult Unilateral Moyamoya Disease with Multiple Unruptured Intracranial Aneurysms: A Case Report]. AB - Adult unilateral moyamoya disease with intracranial aneurysm is frequently reported in the literature, but there is much variation in its treatment. In this case report, we describe the time course and treatment regimen of a patient with moyamoya disease and review the literature regarding moyamoya disease with intracranial aneurysm. A 64-year-old man had untreated intracranial aneurysm and unilateral moyamoya disease for 10 years. He presented with sudden-onset right hemiparesis and aphasia due to a subcortical hemorrhage. He was admitted to the local neurosurgical unit, and upon resolution of symptoms, he was admitted to our hospital. A cerebral angiogram revealed the champagne bottleneck sign of the left carotid artery and obliteration of the top of the left intracranial carotid artery with a moyamoya phenomenon. Two unruptured intracranial aneurysms were identified in the anterior communicating artery(Acom A) and the right intracranial carotid artery(C3). We performed superficial temporal artery-middle cerebral artery anastomosis followed by aneurysmal neck clipping of the Acom A aneurysm. Postoperative imaging showed no new ischemic damage and improved cerebral blood flow. Although the patient experienced temporal worsening of aphasia, his function recovered a few months later and he was able to resume his normal daily life activities. The combination of direct bypass surgery and aneurysmal neck clipping might be a therapeutic option for hemorrhagic unilateral moyamoya disease with unruptured intracranial aneurysm. PMID- 26856266 TI - [Recurrent Hiccups Caused by Malposition of the Peritoneal Catheter of a Lumboperitoneal Shunt: A Case Report]. AB - A number of rare and unpredictable shunt-related complications after shunt placement to treat hydrocephalus have been described. Here a 78-year-old man who underwent lumboperitoneal (LP) shunt placement presented postoperatively with recurrent hiccups. Abdominal radiography and computed tomography performed at 7 days postoperative revealed that a peritoneal catheter had migrated into the upper abdominal cavity and contacted the diaphragm. The patient underwent LP shunt revision, during which the catheter was pulled back and repositioned within the lower abdominal cavity. The hiccups ceased completely. To our knowledge, the only other report of a similar complication was published in the 1980s. Here we describe a case in which a peritoneal catheter from an LP shunt migrated into the upper abdominal cavity and irritated the diaphragm, causing recurrent hiccups. PMID- 26856267 TI - [A Case of Traumatic Vertebral Arteriovenous Fistula Treated by Internal Trapping of the Vertebral Artery]. AB - BACKGROUND: Traumatic vertebral arteriovenous fistula (TVAVF) is an uncommon disease that occurs after traumatic injury. Here we report a case of TVAVF presenting with cervical bruit successfully treated by internal trapping using coils. CASE PRESENTATION: A 66-year-old man was transferred to our hospital after falling into a ditch. Initial CT revealed a C2 fracture into the right transverse foramen, and the patient had been treated with conservative management. A vascular abnormality was suspected because the patient exhibited cervical bruit on admission. CT angiography revealed right TVAVF at the V2 segment of the right vertebral artery (VA) near the C2 fracture. Digital subtraction angiography also revealed right TVAVF between the V2 segment of the right VA and the vertebral venous plexus, draining into the right internal jugular vein and the deep cervical vein as well as the intracranial venous system. The fistula was also opacified by retrograde flow from the contralateral VA through the union, while the flow in the basilar artery was antegrade. The patient was diagnosed with TVAVF with large transection of the right VA, and underwent endovascular treatment with internal trapping of the right VA using coils starting distal to the transection and proceeding in a proximal direction. After treatment, the right VAVF and right VA were completely occluded. The patient achieved clinical symptom resolution with no neurological deficits. CONCLUSION: Endovascular treatment with internal trapping of the VA using coils is safe and effective against TVAVF. PMID- 26856268 TI - [A Case of Aplastic or Twig-Like Middle Cerebral Artery Presenting with an Intracranial Hemorrhage Two Years after a Transient Ischemic Attack]. AB - Aplastic or twig-like middle cerebral artery (Ap/T-MCA) is a rare anatomical anomaly, which can be associated with intracranial hemorrhage and cerebral ischemia. A 52-year-old woman who presented with sudden headache was admitted to our hospital. Computed tomography (CT) and magnetic resonance imaging showed no abnormality; however, magnetic resonance angiogram revealed an occlusion or severe stenosis in the left middle cerebral artery. Three-dimensional CT angiography demonstrated severe stenosis in the left middle cerebral artery. The patient was discharged without any neurological deficit; however, she subsequently complained of temporary weakness in the right hand. It was possibly due to a transient ischemic attack; therefore, cilostazol 200 mg/day was administered for prevention of cerebral ischemia. Single photon emission computed tomography(with or without administration of acetazolamide)showed neither significant decrease in the cerebral blood flow nor cerebrovascular reactivity; hence, surgical revascularization was not performed. However, two years after the initial admission, she was urgently admitted to our hospital with sudden headache and nausea followed by aphasia and weakness of the right extremities. CT images showed diffuse subarachnoid hemorrhage and intracerebral hemorrhage in the left temporo-parietal lobe. Cerebral angiography revealed that the left middle cerebral artery was Ap/T-MCA without cerebral aneurysms. The patient was treated conservatively, and she eventually recovered without any neurological deficit except mild aphasia. Since Ap/T-MCA is associated with both hemorrhagic and ischemic stroke, antiplatelet therapy should be administered carefully. Moreover, it is necessary to consider extracranial-intracranial bypass to reduce hemodynamic stress on the abnormal vessels. PMID- 26856261 TI - Genomic insights into the Ixodes scapularis tick vector of Lyme disease. AB - Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ~57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent. PMID- 26856269 TI - [A Case Report of Stereotactic Craniotomy for the Cerebral Cavernous Angioma]. AB - A 59-year-old woman presented with right sensory loss and right hemiparesis. In February 2013, she was admitted to Araki Neurosurgical Hospital. A magnetic resonance imaging was performed that revealed a left temporal lobe hemorrhage. The image also showed a chronic stereotype hematoma. After 14 days of hospitalization, she underwent a stereotactic craniotomy. Subsequently, by postoperative pathological evaluation, the hematoma was diagnosed as a cavernous angioma. She had no postoperative complications. She was provided rehabilitation support and was discharged 28 days after the admission following which she rejoined work. A stereotactic craniotomy device is very useful in surgeries involving deep lesions. We present a case of stereotactic craniotomy and a few investigation reports. PMID- 26856270 TI - [Non-Specific Back Pain due to Superior Cluneal Nerve Entrapment Neuropathy Treated with Neurolysis: A Case Report]. AB - A 43-year-old man with a 10-year history of low back pain (LBP) had been conservatively treated elsewhere with medications for non-specific back pain. He presented to our institute with LBP and difficulty in standing up, sitting down, and sitting for prolonged periods. His Numerical Rating Scale score, due to LBP, was 8 out of 10. He had numbness on the lateral aspect of his left thigh. A lumbar radiography and magnetic resonance imaging studies revealed mild degenerative changes and mild canal stenosis in the lumbar spine. Palpation over the left posterior superior iliac crest, 8 cm from the midline over the iliac crest, revealed severe tenderness. A superior cluneal nerve(SCN)block performed at the trigger point in both the buttocks resulted in complete pain abatement and disappearance of the radiating pain. Therefore, we diagnosed SCN entrapment neuropathy(SCNE). However, the pain reappeared a few days later and subsequent treatments failed to relieve it; therefore, we decided to perform surgery. The SCN penetrates the thoracolumbar fascia through an orifice just before crossing over the iliac crest. We opened the orifice with microscissors in a distal to rostral direction along the SCN and released the entrapped nerve. After surgery, the symptoms were relieved and the patient experienced no recurrence in the last 4 years after the treatment. SCNE should be considered as a causative factor of LBP, and its treatment using minimally invasive surgery yields excellent clinical outcome. PMID- 26856271 TI - [Update Knowledge for Brain Tumors (4) Oligodendroglial Tumors]. PMID- 26856272 TI - Theoretical Aspects of GPCR-Ligand Complex Pharmacology. AB - Over the past 50 years in pharmacology, an understanding of seven transmembrane (7TMR) function has been gained from the comparison of experimental data to receptor models. These models have been constructed from building blocks composed of systems consisting of series and parallel mass action binding reactions. Basic functions such as the the isomerization of receptors upon ligand binding, the sequential binding of receptors to membrane coupling proteins, and the selection of multiple receptor conformations have been combined in various ways to build receptor systems such as the ternary complex, extended ternary complex, and cubic ternary complex models for 7TMR function. Separately, the Black/Leff operational model has furnished an extremely valuable method of quantifying drug agonism. In the past few years, incorporation of the basic allosteric nature of 7TMRs has led to additional useful models of functional receptor allosteric mechanisms; these models yield valuable methods for quantifying allosteric effects. Finally, molecular dynamics has provided yet another new set of models describing the probability of formation of multiple receptor states; these radically new models are extremely useful in the prediction of functionally selective drug effects. PMID- 26856273 TI - Frequency of MED12 mutations in phyllodes tumors: Inverse correlation with histologic grade. AB - Phyllodes tumor (PT) is a rare breast biphasic tumor with a potential risk of recurrence and metastasis. In this study, the frequency of MED12 mutations in 176 PTs (49 benign, 49 borderline, and 78 malignant) was determined and the prognostic effect of these mutations in malignant type PT was evaluated. Analysis of MED12 mutations was performed by Sanger sequencing targeting the hotspot mutation region (exon 2) of MED12. Immunohistochemistry was also applied for evaluation of MED12 protein expression on tissue microarray blocks for 133 PTs including 50 benign, 50 borderline, and 33 malignant cases. A notable difference in the frequency of MED12 mutations was found according to histologic grade (71.4% of benign PTs, 51% of borderline PTs, 26.9% of malignant PTs; P < 0.001). MED12 protein expression was not correlated with MED12 mutation status. Patients with malignant PTs that harbored MED12 mutations demonstrated improved disease free survival (DFS) compared with those without MED12 mutation (P = 0.07). MED12 mutation was a common molecular alteration in PT and the frequency of MED12 mutation decreased with increasing histologic grade. In malignant PT, MED12 exon 2 mutations showed improved DFS but without significance. (c) 2016 Wiley Periodicals, Inc. PMID- 26856275 TI - Awareness, knowledge and perception of chronic kidney disease in a rural community of South-West Nigeria. AB - BACKGROUND: Awareness and education on kidney disease impact on its effective management and will reduce the significant economic and public health burden. Knowledge of CKD and risk factors increases the perception of being at high risk and increasing health seeking behavior. We conducted a cross-sectional descriptive study to assess the level of awareness, knowledge and conventional risk factors of CKD in the community to strategize on preventive modalities using the information gathered from this population. METHODS: We used a pretested structured questionnaire to draw information on sociodemography, knowledge and risk factors of CKD from 563 residents aged >18 years. RESULTS: A total of 454 residents completed this study, mainly farmers, with a mean age of 45.8 +/- 19.0 years and male: female ratio of 0.8:1. Only 33.7% had heard of kidney disease with 59.3% from the media and 35.3% from health workers; the level of knowledge of CKD was good in 27.1%. The majority (67.0%) do not know the correct location of the kidneys. Only 10.6% could mention at least one function of the kidneys with only 24.5% agreeing that NSAIDs can cause kidney disease. A laboratory test for kidney function was known by 4.4%; 45.9% and 47.8% believe that CKD can be cured by spiritual means and herbal concoctions respectively. Only 11.1% agreed that CKD can be hereditary. Abdominal obesity and cigarette smoking were seen in 14.6% and 16.6% respectively. Hypertension was seen in 26.5% while 17.8% actually knew they were hypertensive. Diabetes mellitus was found in 3.4%. None of the patients with CKD who had diabetes or hypertension was aware of kidney disease. CONCLUSION: There are a misconception and low level of awareness and knowledge of CKD, including those with risk factors, in the community. Efforts should be made to create awareness and educate people on CKD and prevention of its risk factors. PMID- 26856274 TI - A Review of Natural Stimulant and Non-stimulant Thermogenic Agents. AB - Obesity and overweight are major health issues. Exercise and calorie intake control are recognized as the primary mechanisms for addressing excess body weight. Naturally occurring thermogenic plant constituents offer adjunct means for assisting in weight management. The controlling mechanisms for thermogenesis offer many intervention points. Thermogenic agents can act through stimulation of the central nervous system with associated adverse cardiovascular effects and through metabolic mechanisms that are non-stimulatory or a combination thereof. Examples of stimulatory thermogenic agents that will be discussed include ephedrine and caffeine. Examples of non-stimulatory thermogenic agents include p synephrine (bitter orange extract), capsaicin, forskolin (Coleus root extract), and chlorogenic acid (green coffee bean extract). Green tea is an example of a thermogenic with the potential to produce mild but clinically insignificant undesirable stimulatory effects. The use of the aforementioned thermogenic agents in combination with other extracts such as those derived from Salacia reticulata, Sesamum indicum, Lagerstroemia speciosa, Cissus quadrangularis, and Moringa olifera, as well as the use of the carotenoids as lutein and fucoxanthin, and flavonoids as naringin and hesperidin can further facilitate energy metabolism and weight management as well as sports performance without adverse side effects. (c) 2016 The Authors Phytotherapy Research published by John Wiley & Sons Ltd. PMID- 26856276 TI - Knowledge and practice of prophylaxis of deep venous thrombosis: A survey among Nigerian surgeons. AB - BACKGROUND: Venous thromboembolism is a potentially dangerous condition that can lead to preventable morbidity and mortality among surgical patients. OBJECTIVES: We aimed to determine the knowledge and practice of surgeons practising in Tertiary Hospitals in Nigeria about prophylaxis of deep vein thrombosis (DVT). MATERIALS AND METHODS: Eight Tertiary Institutions were selected from institutions in the geopolitical regions of the country by simple random sampling using balloting method. A semi-structured questionnaire was administered, and the response was obtained from 105 out of 254 surgeons. RESULTS: The mean knowledge score was 5.81 +/- 1.67, and only 33.3% have good knowledge about DVT prophylaxis. No statistical difference was observed between the different groups of surgeons. The mean practice score was 5.19 +/- 1.8 and only 20% of surgeons have a good practice of DVT prophylaxis. The majority (90.5%) have encountered DVT whereas 83.5% have encountered pulmonary embolism in their practice. Most commonly encountered risk factors include prolonged immobility, advanced age, and pelvic surgery. Only 13.3% have used Well's score in the clinical evaluation of their patients. The prophylactic modality adopted varies, but most surgeons (77%) utilized both the pharmacological and mechanical methods. Low molecular weight heparin is the commonly used chemoprophylactic agent while a combination of early ambulation and limb physiotherapy is the most commonly preferred mechanical method of thromboprophylaxis. CONCLUSION: There is a deficiency in the knowledge and practice of DVT prophylaxis among surgeons in Nigeria. There is a need to improve both the knowledge and practice by introducing institutional guidelines or protocol for DVT prophylaxis for surgical patients. PMID- 26856277 TI - Comparative sonographic evaluation of the anteroposterior dimensions of the pancreas in diabetics and nondiabetics. AB - BACKGROUND: The pancreas is an insulin-producing gland and is prone to varying degrees of destruction and change in patients with diabetes mellitus (DM). Various morphological changes including reduction in the pancreas dimensions have been described in DM. OBJECTIVES: To determine pancreatic anteroposterior (AP) dimensions in diabetics by sonography and compare with nondiabetics. To also evaluate the correlation of the AP dimensions with patient's anthropometry, as well as the duration of the disease in comparison with nondiabetics. MATERIALS AND METHODS: This is a comparative cross-sectional study involving 150 diabetics with 150 sex and age matched healthy normoglycemic group used as controls. Sonographic measurements of the AP dimensions of the pancreatic head, body, and tail of both study groups were performed with the use of 3.5 MHz curvilinear array transducer of a SonoAce X4 ultrasound machine. Data were analyzed using Statistical Package for Social Sciences version 17 (SPSS Inc., Chicago, IL, USA). A statistical test was considered significant at P <= 0.05 and 95% confidence interval. RESULTS: Pancreas AP dimensions were significantly smaller in diabetics compared to those of the controls. The mean dimensions were 1.91 +/- 0.26 cm, 0.95 +/- 0.12 cm, and 0.91 +/- 0.11 cm for the head, body, and tail, respectively, in diabetics and 2.32 +/- 0.22 cm, 1.43 +/- 0.19 cm, and 1.34 +/- 0.20 cm in the control (P < 0.001 in all cases). The dimensions were also significantly smaller in the Type 1 diabetics compared to Type 2 (P < 0.001 in all cases). The mean duration of illness for the Types 1 and 2 diabetics were 3.09 +/- 1.38 and 3.78 +/- 3.12 years, respectively. Longer duration of illness was associated with smaller pancreas body and tail dimensions, while pancreas head dimension was not significantly affected by the duration of illness. CONCLUSION: Diabetics have smaller pancreas AP dimensions compared to the normal population. PMID- 26856278 TI - Contraceptive knowledge and practice among senior secondary schools students in military barracks in Nigeria. AB - BACKGROUND: Many adolescents lack adequate health education coupled with low contraceptive use. As a result of this, they may experience the negative health consequences of early, unprotected sexual activity as well as its social and economic implications. OBJECTIVE: To determine the level of knowledge of contraceptives and its use among senior secondary schools students in Ojo military barracks, Lagos. METHODOLOGY: A cross-sectional study of 400 senior secondary schools students in Ojo military barracks, Lagos, selected using the multistage sampling technique was done. Data were collected using pretested, self administered structured questionnaires. The data were analyzed using Statistical Package for Social Sciences version 17 (International Business Machine USA). Tests for statistical significance were carried out using Chi-square tests for proportions. P < 0.05 was considered significant. RESULTS: The response rate was 100%. Majority of them 391 (97.8%), were in the adolescent age group (10-19 years). The mean age was 15 +/- 2.4 for males and 15 +/- 2.2 for the females. Two hundred and seventy (67.5%) of them had correct knowledge of the use of condoms while 48 (31.1%) of the sexually active respondents have ever used any form of contraceptive with no statistically significant difference between the male and female respondents (P = 0.338). The most common barrier to contraceptive methods as reported by 131 (85.1%) of respondents was their being too embarrassed to source for the commodities. CONCLUSIONS: There was a fairly high level of knowledge and relatively low use of contraceptives. We recommend that efforts should be intensified to promote the safe sexual practice and contraceptive use in this age group. PMID- 26856279 TI - The role of neoangiogenesis and vascular endothelial growth factor in the development of carpal tunnel syndrome in patients with diabetes. AB - OBJECTIVE: Carpal tunnel syndrome (CTS) is an entrapment neuropathy which is caused by the disruption of blood supply in the median nerve under transverse carpal ligament. Systemic factors facilitate the formation of the syndrome. In this study, neovascularization in the subsynovial tissue and proliferative activity in the stroma are analyzed within the cases of diabetic and idiopathic CTS. MATERIALS AND METHODS: Subsynovial connective tissue samples of 30 diabetes mellitus patients with CTS and 30 patients with idiopathic CTS were evaluated. Vascular endothelial growth factor (VEGF), CD31, CD34, Factor VIII-related antigen, and smooth muscle actin (SMA) was used to make a comparative study of neovascularization. Proliferative index was assessed using anti-Ki-67 antibody. RESULTS: As a result of the proliferation of endothelial elements, de novo blood vessel formations in the subsynovial tissue were assessed by vascular markers. Significant neovascularization was seen in diabetic group for VEGF, CD31, SMA (P < 0.01); and for CD34 (P < 0.05) when compared with idiopathic CTS group. In addition, more intense positive staining for CD34, SMA (P < 0.01); and for VEGF (P < 0.05) was found at isolated stromal cells of diabetic CTS group against idiopathic CTS group. Significantly high proliferative index in subsynovial connective tissue with Ki-67 was observed the diabetic group (P < 0.01). CONCLUSION: VEGF expression has an importance within CTS pathogenesis. Increased ischemia-reperfusion damage, neoangiogenesis, and VEGF expression has an important role frequently CTS occurrence in diabetic patients. Our study supports enhancement in VEGF expression similar to changes in diabetic nephropathy and retinopathy in the neovascularization within the subsynovial connective tissue in the cases of diabetes. PMID- 26856280 TI - Correlation of the association of serum lactate, random blood sugar, and revised trauma score as predictors of outcome in hemodynamically unstable abdominal emergencies. AB - BACKGROUND: Elevated levels of serum lactate and glucose during resuscitation have been demonstrated to be predictors of morbidity and mortality in hemodynamically unstable patients with surgical abdominal conditions. However, the rate of return to normal levels of both lactate and blood glucose may be better predictors of mortality and morbidity. The aims of this study are: (I) To determine the pattern of serum lactate and glucose changes in patients with surgical abdominal conditions requiring resuscitation within 48 hours of presentation. (II) To correlate the predictive capability of these two independent parameters. (III) To correlate the predictive values of these parameters with the revised trauma score (RTS). PATIENTS AND METHOD: This is a prospective observational study conducted over three months. The patients admitted by the general surgery division requiring resuscitation from shock was included in this study. Resuscitation was carried out with crystalloids. The estimation of serum lactate and glucose levels was done at presentation (0 hours), 12, 24 and 48 hours after admission. The revised trauma score (RTS) was calculated for each patient at presentation and at 12, 24 and 48 hours subsequently. The patients were followed up four weeks or when death occurred within four weeks of presentation. RESULTS: Forty four patients were recruited in the study. There were seven mortalities. The mean serum levels of Plasma glucose and lactate of all the patients were elevated at presentation in the emergency department. CONCLUSION: Survival was better with a return to normal serum lactate within 12 hours. On the other hand the random plasma glucose (RPG) levels may not be useful in prognosticating patients. However a combination of serum lactate, RTS (at 24 and 48 hours) and RPG at 48 hours may improve predictive parameters in trauma related cases. PMID- 26856281 TI - Topical-intracameral anesthesia in manual small incision cataract surgery: A pilot study in a Tertiary Eye Care Center in Africa. AB - BACKGROUND: Cataract remains a leading cause of blindness worldwide. Manual small incision cataract surgery (MSICS) is currently practiced as the technique of choice in Sub-Saharan Africa to reduce the backlog of cataract blindness. Optimal pain control during surgery remains a challenge to cataract surgeons. AIM: To evaluate the efficacy and safety profile of the use of aqueous topical/intracameral anesthesia in MSICS. MATERIALS AND METHODS: In this hospital based case series, consecutive patients presenting at the eye clinic with operable cataract and willing to have surgery were enrolled. Baseline sociodemographics (age, sex, and occupation), type of cataract by morphology, pain perception, and surgeons experience were recorded. Descriptive and comparative statistical analyses were performed. A P < 0.05 was considered statistically significant. RESULTS: The surgeries were performed on 30 eyes of 16 (53.3%) males, and 14 (46.7%) females (sex ratio, 1:0.9) who were aged 60.3 +/- 16.32 standard deviation (SD) (95% confidence interval [CI] of mean; 53.94-66.13) (range; 20-98 years). Using the visual analog scale, the mean pain score was 2.7 SD +/- 2.215 (1.87-3.53 95% CI). There was no correlation between degree of pain perception and gender (P = 0.806) or age (P = 0.388). Patient's cooperation was excellent in 22 (73.3%) of patients. Intraoperative complications occurred in 3 (10%) of patients. CONCLUSION: The mean pain score in this study is low. There is no correlation between perception of pain with gender or age. Surgeons experience is excellent in most of the cases. This method of anesthesia in MSCIS is adequate for patient's comfort and safe cataract surgery. PMID- 26856282 TI - Ischemic priapism in South-East Nigeria: Presentation, management challenges, and aftermath issues. AB - CONTEXT: Ischemic priapism is the more common variety of priapism and often presents late. Outcome is largely dependent on the duration of ischemia. AIMS: To determine the etiology, presentation, management, and outcome of ischemic priapism. SETTINGS AND DESIGN: Retrospective analysis of consecutive cases presenting to three hospitals offering specialist urological services in South East Nigeria from January 2000 to December 2010. PATIENTS AND METHODS: Fifteen patients were assessed for clinical data and outcome. STATISTICAL ANALYSIS USED: The data were analyzed descriptively and inferentially using Statistical Package for Social Sciences (SPSS version 16, SPSS Inc., Chicago IL, USA) with P < 0.05. RESULTS: Mean age was 30.5 years (standard deviation [SD] =1.63), range: 14-79 years. Onset to presentation interval ranged from 6 h to 28 days. Eight patients (53.3%) had sickle cell disease (SCD). Four patients (26.7%) had unidentified causes. The 8 SCD patients had stuttering priapism on several occasions previously. Six patients (40%) had taken oral herbal medications as treatment prior to presentation. Initial resuscitative measures were intravenous hydration, aspiration, and irrigation with normal saline in 13 patients. Glanulo-cavernous shunt (Al-Ghorab) was performed in all the patients. Detumescence was immediate in 14 and delayed in 1 patient. Three patients had transient recurrence of tumescence, while one had to be reshunted. Erectile dysfunction (ED) occurred in 7 patients (46.7%). Occurrence of ED increased significantly in patients presenting 24 h after onset of symptoms ([P = 0.032] Fishers exact test). Mean duration of follow-up was 21.9 weeks (SD = 4.1), range: 3-156 weeks. CONCLUSIONS: Low flow priapism is common in our environment, and approximately half will occur in SCD patients who have had stuttering priapism previously. Timely diagnosis and treatment will reduce the probability of severe ED. In our experience, the Al Ghorab shunt provides rapid relief. Enlightenment is vital in reducing ischemia time. Emphasis on preventive measures in SCD patients is vital. PMID- 26856283 TI - Low back pain as seen in orthopedic clinics of a Nigerian Teaching Hospital. AB - BACKGROUND: Low back pain is not a specific disease though a common health concern worldwide. There is regional variation in its etiology and patterns of presentation. In West African sub-region, there are very limited data on this important aspect of low back pain. OBJECTIVE: We aimed to determine the etiology and pattern of presentation of low back pain among patients seen in our orthopedic outpatient clinics. MATERIALS AND METHODS: This was a retrospective review of database of all new patients with low back pain seen at the orthopedics clinics of Federal Teaching Hospital, Abakaliki between 2003 and 2013. RESULTS: There were 2914 new patients seen in the orthopedic clinics -291 (10%) of them presented with low back pain. The female to male ratio was 1:1.04 and the mean age was 45.8 +/- 1.67 years. The mechanical low back pain was involved in 82.1% of the patients, and the incidence was significantly higher in females than males (53.1% vs. 46.9%, P < 0.003). The males were significantly more afflicted than females by pain from spinal infections (58.3% vs. 41.7%) and tumors (92.3% vs. 7.7% P <0.003). Low back pain associated with radiculopathy was observed in 75 (25.7%) patients and the incidence was significantly higher in the married than the singles (30.2% vs. 13.9%, P < 0.005). Lifting of heavy object was the most common predisposing factor of low back pain. Hypertension and peptic ulcer disease were two top medical co-morbidities while osteoarthritis of hip and knee was the most common associated musculoskeletal disorders. CONCLUSION: Low back pain of mechanical origin (recurrent and chronic in a significant proportion of patients) is predominant in our environment. This pattern calls for prevention as well as the early and appropriate care of the patient with low back pain. PMID- 26856284 TI - Influence of different surface treatments on push-out bond strengths of fiber reinforced posts luted with dual-cure resin cement. AB - OBJECTIVES: The objective was to evaluate whether fiber postsurface conditioning with air abrasion or erbium:yttrium-aluminum-garnet (Er:YAG) laser would influence the bond strength of dual-cure resin cement to the fiber-reinforced (FRC) posts. MATERIALS AND METHODS: Twenty-one FRC posts were divided into three groups according to surface treatment methods as follows: An untreated control group air abrasion with Al2O3group, and Er:YAG laser treated group with 150 mJ parameter. Fiber posts were then built up to dual-cure resin cement. Eighteen specimens were set and sectioned perpendicularly along the long axis of the post using a saw. Two disks (thickness of 2 mm) were obtained from each specimen (n = 12). Remaining three posts were stored for scanning electron microscopic evaluation. Push out test was performed on the each specimen and the values were recorded as MPa. The data were analyzed using one-way analysis of variance and Tukey post-hoc tests (P < 0.05). RESULTS: The bond strength values for the groups were as follows: Control (15, 28 MPa), air abrasion group (19, 73 MPa), and Er:YAG group (17, 84 MPa). Air abrasion affected the bond strength significantly (P < 0.05). CONCLUSION: Air abrasion attained higher bond strengths when FRC posts were luted to dual-cure resin cement. Additional studies should be designed with different types and parameters of laser devices to understand the effect of these devices on bond strength. PMID- 26856285 TI - Retrospective evaluation of patients at follow-up with acute poisoning in Intensive Care Unit. AB - OBJECTIVE: Poisonings are among the major causes of emergency visits and intensive care hospitalizations. The aim of our study is to evaluate intoxicated patients at follow-up and treated in the Intensive Care Unit (ICU) in terms of demographic characteristics, type of poisonings and results of treatment. MATERIALS AND METHODS: Patients at follow-up aged 17 or older admitted with intoxication to the ICU between January 1, 2009 and December 31, 2011 were included in the study. Age, gender, presenting symptoms, duration of hospitalization, type of poisoning, the way of poisoning, medical history, seasons, hospitalization costs, treatment and prognosis of the patients were analyzed. RESULTS: Totally, 153 (8.9%) out of 1375 follow-up patients in the ICU had acute intoxication. The mean age of intoxicated patients was 29.4 +/- 11, 68% of them were female, 78.4% of them were under 35 years old, and intoxication was most common in the 17-25 age group. 114 of them (94.1%) were suicidal. The most common cause of poisoning was drug-poisoning by 88.2%, and most common presenting symptoms were nausea and vomiting by 71.2%. Mean length of stay was 2.4 +/- 1.6 days, and the average cost of hospitalization was 761 +/- 884 Turkish Liras or 271 +/- 315 USD. 5 patients (3.3%) were intubated because of respiratory failure. There was no mortal case. CONCLUSION: Suicide attempts are prominent in acute poisoning, and the young female population is at higher risk. It was found that drugs, particularly antidepressants and antipsychotic agents were the most common cause of poisoning. The high cost of treatment of acute intoxication cases is a major cause of economic burden. Clinicians should be more careful when prescribing such drugs. PMID- 26856286 TI - Evaluation of correct knowledge of key danger signs in pregnancy among antenatal clinic attendees at a tertiary health facility in Nigeria. AB - CONTEXT: Test of knowledge of pregnant women on key danger signs as a marker to assess the quality of information shared during health education at the antenatal clinic (ANC) is desirable. AIM: The aim was to assess correct knowledge of danger signs among pregnant women who attend ANC. SETTINGS AND DESIGN: A cross-sectional design conducted among pregnant women at the ANC of the University College Hospital, Ibadan, Nigeria. MATERIALS AND METHODS: A pretested structured questionnaire that contains sociodemographics, past obstetrics history, and a list of test questions to assess correct knowledge of danger signs was administered to each consenting participant. STATISTICAL ANALYSIS USED: Descriptive and bivariate analyses were performed. The knowledge score of key danger signs in pregnancy (KDSP) was measured on a scale of 0-7 and participants were scored as having poor (0-2), fair (3-4), or good (5-7) knowledge. The reliability of the questionnaire to assess knowledge score was determined with Cronbach's alpha. Statistical significance was set 5%. STATA 12.0 Software was used. RESULTS: The mean age of respondents was 30.28 +/- 4.56 with the majority (75.1%) of respondents aged 26-35 years. The Cronbach's alpha was 0.871. In general, the knowledge score was good and the associated factors on bivariate analysis were younger age (P = 0.028), Islamic religion (P = 0.048), ethnicity (P = 0.03), professional occupation (P = 0.01), and previous attendance of health talk on KDSP (P < 0.0001). CONCLUSION: There was a high knowledge score of KDSP, but some still have some misconceptions that need to be addressed. PMID- 26856287 TI - Video-assisted thoracic surgery in a Nigerian teaching hospital: Experience and challenges. AB - BACKGROUND: Video-assisted thoracic surgery (VATS) is well established. Its application in Nigeria has however been limited and not been reported. The aim of this study was to describe our institutional experience and challenges with VATS. MATERIALS AND METHODS: This was a retrospective cross-sectional study of all patients that underwent VATS in our institution between March 2008 and June 2013. Data were extracted from a prospectively maintained database. RESULTS: Two hundred and sixty-one patients were assessed as potential VATS cases. VATS was initiated in 26 patients, but completed in 25 patients (9.6%) as there was one case of conversion of a planned VATS bullectomy due to the failure of one lung ventilation. There were 12 males and 13 females. Mean age was 40.7 +/- 13.9 years. The indication was interstitial lung disease in 9 patients (36%), malignant pleural effusion in 6 patients (24%), spontaneous pneumothorax in 5 patients (20%), indeterminate pulmonary nodule in 2 patients (8%), pleural endometriosis in 2 patients (8%) and bronchogenic cyst in one patient (4%). Procedures performed were lung biopsy in 13 patients (52%), pleural biopsy and pleurodesis in 6 patients (24%), bullectomy and pleurodesis in 5 patients (20%) and excision of bronchogenic cyst in one patient (4%). Mean hospital stay was 4 +/- 0.7 days. There were no complications and no mortalities. CONCLUSION: VATS is being performed in our institution with successful outcomes. The use of VATS in Nigeria is encouraged. The relatively high cost of VATS is, however, a major limitation to more widespread use. PMID- 26856288 TI - Frequency and clinical impact of ETV6/RUNX1, AF4-MLL, and BCR/ABL fusion genes on features of acute lymphoblastic leukemia at presentation. AB - BACKGROUND: Variations in disease presentation and outcome of leukemia treatment has been associated with the presence of certain mutant genes. Three major translocations (ETV6-RUNX1, BCR-ABL, and AF4-MLL) in acute lymphoblastic leukemia (ALL) have been shown to affect treatment outcome. This study is aimed at assessing the relationship between these translocations and the presence of other indicators of disease severity (white cell count, hemoglobin concentration, platelet count, and hematocrit) in ALL. PATIENTS AND METHODS: Forty chemotherapy naive patients aged between 9 months and 54 years had their marrow samples analyzed for the prevalent mutations. Their clinical and laboratory details on presentation were also obtained. RESULTS: Abnormal genes detected were BCR/ABL1 major transcript in 5 (12.5%), ETV6/RUNX1 in 2 (5.0%), MLL/AF4 none and none of the patients had more than one fusion gene. There was no relationship between the presence of these fusion genes and the clinical and laboratory features of ALL. An association exists between the fusion genes and ethnic origin of the patients (P = 0.005). There is no significant association between the abnormal fusion genes detected and some laboratory features of prognostic importance, which include total white blood cell count (P = 0.416) and FAB subtype (P = 0.576). CONCLUSION: Presence of fusion the genes BCR/ABL1, ETV6/RUNX1, and MLL/AF4 does not have any impact on the clinical and laboratory features of ALL at presentation. PMID- 26856289 TI - Effect of whitening toothpastes on bonding of restorative materials to enamel of primary teeth. AB - OBJECTIVE: The aim of this in vitro investigation was to measure shear bond strength (SBS) of a resin composite and a resin-modified glass ionomer to enamel of primary teeth after application of different whitening toothpastes (WTs). MATERIALS AND METHODS: Eighty labial enamel surfaces of primary incisors were randomly distributed into 8 groups of 10 each according to the surface treatment and bonding material. G1 and G2, control (brushed with water without WT); G3 and G4, (brushed with Colgate Optic White WT [Colgate-Palmolive Company, New York, NY, USA]), G5 and G6, (brushed with Crest Pro-Health Whitening WT [Procter and Gamble, Cincinnati, OH, USA]) and G7 and G8, (brushed with Arm and Hammer Advance White Extreme Whitening with Stain Defense WT [Church and Dwight Co., Princeton, NJ, USA]). SBS was measured at a crosshead speed of 0.5 mm/min and the type of bond failure was assessed using a stereomicroscope. RESULTS: There was significant difference between SBS of composite resin in groups 1, 3, 5, and 7 (P < 0.001), but no difference between resin-modified glass ionomer in groups 2, 4, 6, and 8 (P < 0.056). SBS of group 1 (control) was greater than groups 3, 5, and 7. There was a significant difference between group 1 and group 2 as well as group 7 and group 8 (P < 0.001). CONCLUSIONS: WTs affect SBS of resin composite, but not resin-modified glass ionomer to enamel of primary teeth. No difference of failure modes between different groups of tested materials. PMID- 26856290 TI - Assessment of intraoral image artifacts related to photostimulable phosphor plates in a dentomaxillofacial radiology department. AB - OBJECTIVE: The aim of the present study was to evaluate the presence, frequency, and causes of artifacts in intraoral images obtained using photostimulable phosphor (PSP) plates. MATERIALS AND METHODS: A total of 11,443 intraoral images, including 4291 periapical and 7152 bitewing images, acquired over a 6-month period as well as over a month 1-year after the initial imaging were evaluated by a single observer and image artifacts only related to the PSP system were recorded. Before the study, an experienced dentomaxillofacial radiologist and a research assistant assessed a set of image artifacts and agreed on the causes of these artifacts. All unidentified artifacts were reassessed by both researchers before the final decision. The data were analyzed using the statistical software SPSS 11.5. RESULTS: The total number of images with one or more artifacts was 2344 (20.4%). Of these, 2008 were of adult patients and 336 were of pediatric patients. While movement of the phosphor plate in the disposable pocket was the most common cause of the observed image artifacts in the children, non-uniform image brightness was the most frequently observed artifact in the case of the adults. CONCLUSION: The percentage of images with artifacts in the 6th month was lower than that during the 1st month. More significantly, the lowest percentage was obtained 1-year after the initial imaging, owing to the increase in familiarity with the system. Understanding the reasons for the image artifacts and studying ways of preventing are of high clinical importance. PMID- 26856292 TI - Using cone beam computed tomography to examine the prevalence of condylar bony changes in a Turkish subpopulation. AB - BACKGROUND/PURPOSE: The aim of this study was to characterize the condylar bone changes in the temporomandibular region using cone-beam computed tomography (CBCT) and to determine the prevalence of these changes in a population. MATERIALS AND METHODS: CBCT images of the temporomandibular joints (TMJs) of 795 patients (426 females, 369 males) were retrieved from the computer database. The cross-sectional, coronal and sagittal views of 1-mm-thick sections of the TMJ were generated using CBCT. Age, gender, and bone changes on both condyles were recorded, and data were analyzed using a Chi-square test and McNemar's test to evaluate comparisons between qualitative data (IBM Corp., Armonk, NY). RESULTS: No bone changes were observed in 78.4% (n = 623) of the TMJ samples obtained from the right side. Osteoarthritic changes were observed in 17.9% (n = 142) and developmental changes in 2.6% (n = 21) of the cases. On the left side, osteoarthritic changes were observed in 11.6% (n = 142) of the cases while developmental changes were observed in 2.6% (n = 21). Moreover, 82.4% (n = 655) of the TMJ samples showed no changes. When the age groups were compared in samples obtained from both right and left TMJs, the prevalence of bone changes increased by the age of 60 years and older. CONCLUSION: The prevalence of degenerative condylar bone changes increased with increasing age and was more frequent in women and right condyle. PMID- 26856291 TI - Frequency of relapse among Nigerian children with steroid-sensitive nephrotic syndrome. AB - BACKGROUND: The clinical course of steroid-sensitive nephrotic syndrome (SSNS) among Nigerian children has rarely been reported; this makes prognostication difficult. OBJECTIVES: The objective was to determine the frequency of relapses including frequent relapses (FR) and steroid-dependence (SD) in a cohort of Nigerian children with SSNS. A secondary objective was to identify clinical and demographic factors associated with relapse in these children. METHODS: Medical records of children with SSNS in a Tertiary Hospital in Nigeria were reviewed. Children with onset of nephrotic syndrome (NS) at age <1-year, follow-up period <12 months and secondary causes of NS were excluded. The relapse status of each child was determined in the 1st and 2nd year after diagnosis and the proportions with no relapse, FR and SD were calculated. RESULTS: Fifty children (68% males; median [range] age at onset of NS 4.8 [1.1-14.9] years) were followed-up for 31.1 (12.1-79.8) months. In the 1st and 2nd year of follow-up, 23 (46%) and 24 (70.6%) children experienced relapse, respectively. In the 1st-year, 0% and 10% had FR and SD while in the 2nd year 2.9% and 11.8% had FR and SD, respectively. Age at onset of NS, gender, time to first remission, serum creatinine or presence of hypertension or microscopic hematuria was not associated with 1st or 2nd year relapse. CONCLUSION: About half and two-thirds of children with NS in our center experience relapse in the 1st and 2nd year of follow-up, respectively; much fewer proportions experienced FR and SD in these periods. None of the commonly reported demographic and clinical factors was associated with NS relapse. PMID- 26856293 TI - Influence of different final irrigation regimens and various endodontic filling materials on vertical root fracture resistance. AB - AIM: The aim of this study was to evaluate the influence of different endodontic materials and final irrigation regimens on vertical root fracture (VRF) resistance. MATERIALS AND METHODS: Eighty human teeth were prepared then assigned into two groups (n = 40) according to the final irrigations. G1: 5 mL, 5.25% sodium hypochlorite (NaOCl), G2: 5 mL, 2% chlorhexidine gluconate (CHX). Each group was assigned into four subgroups according to the obturation system used (n = 10): A: iRoot SP/single gutta-percha cone (SGP), B: Only iRoot SP, C: Mineral trioxide aggregate (MTA)-Fillapex/SGP, D: AH26/SGP. The specimens were embedded in acrylic molds and subjected to compressive loading at a rate of 1 mm min until VRF occurred. Data were analyzed via three-way ANOVA tests. RESULTS: The statistically significant difference was found among groups (P < 0.05). The G1A and G1B and G1D revealed significantly higher-VRF values than G1C (P = 0.023). The roots filled with MTA-Fillapex revealed lower-VRF values than the other subgroups (P < 0.05). Groups irrigated with NaOCl had significantly lower-VRF values than the groups irrigated with CHX (P < 0.05). CONCLUSION: Final irrigation regimens could alter VRF resistance of root canals filled with different obturation technique and root canal sealers. PMID- 26856294 TI - Self-perceived oral health and whole salivary immunoglobulin G levels in habitual gutka-chewers and nonchewers. AB - OBJECTIVE: To assess self-perceived oral health and whole salivary immunoglobulin G (IgG) levels among habitual gutka-chewers and nonchewers (controls). MATERIALS AND METHODS: Fifty gutka-chewers and fifty controls were included. Demographic data and self-perceived oral health status (pain in teeth, pain on chewing, bleeding gums (BG), bad breath, loose teeth and daily oral hygiene protocols) were collected using a questionnaire. Unstimulated whole saliva (UWS) was collected and unstimulated whole salivary flow rate (UWSFR) was determined. Whole salivary IgG levels were determined using standard techniques. Odds ratios were calculated for oral symptoms and group differences in protein levels were compared using one-way analysis of variance (alpha+/- <5%). RESULTS: BG was more often reported by gutka-chewers than controls (P < 0.05). There was no significant difference in UWSFR and self-perceived pain in teeth, pain on chewing, bad breath and loose teeth among gutka-chewers and controls. IgG levels were significantly higher among gutka-chewers than controls (P < 0.01). Among gutka-chewers, whole salivary IgG levels were comparable individuals with and without self-perceived oral symptoms. Among controls, IgG levels in UWS were significantly higher among individuals who had BG than those who did not (P < 0.05). CONCLUSIONS: Self-perceived oral health is worse and whole salivary IgG levels are higher in gutka-chewers compared to controls. PMID- 26856295 TI - Effects of sevoflurane and propofol on S100beta and neuron-specific enolase protein levels during cardiopulmonary bypass. AB - AIM: Cardiopulmonary bypass (CPB) is associated with the release of S100beta and neuron-specific enolase (NSE) indicating cerebral cell injury. The purpose of the present study was to evaluate the effect of propofol and sevoflurane on S100beta and NSE levels in patients undergoing coronary artery bypass grafting (CABG). MATERIALS AND METHODS: Twenty male patients undergoing CABG were randomly allocated into two groups. One group received sevoflurane (GS) and the other received propofol (GP). Arterial blood samples for analysis of S100beta and NSE levels were taken preoperatively (T1), 30 min after initiation of CPB (T2), at the end of CPB (T3), 1 (T4), 6 (T5) and 24 h (T6) postoperatively. RESULTS: S100beta level was significantly higher compared to all analyzed times at T3 in both groups (P < 0.001). S100beta level was significantly higher in GP than GS only at T2 (P = 0.002). NSE level was significantly higher at T3, T4 and T5 than T1 in the GP (P = 0.001, 0.002 and 0.023, respectively), while a significant increase was seen at T3 and T4 in GS group (P = 0.001 and 0.047, respectively). CONCLUSION: Our findings showed that both S100beta and NSE levels similarly increased during CPB and immediately after CPB during sevoflurane and propofol based anesthesia. PMID- 26856297 TI - Phlegmasia cerulea dolens in a long distance driver. AB - Phlegmasia cerulea dolens (PCDs) is a rare and serious complication of massive deep venous thrombosis of the lower extremities, which has a high mortality rate. It is characterized by the sudden onset of severe leg pain, massive edema, cyanosis, venous gangrene, compartment syndrome and arterial compromise, often followed by pulmonary embolism and death. We report one case of a long distance driver who presented with PCDs, complicated by fatal pulmonary embolism. PMID- 26856296 TI - A comparison of the intensive care experiences of emergency and elective cardiac surgery patients. AB - PURPOSE: The study was planned to review the experiences of patients in the intensive care units (ICUs) and determine their states of awareness following an emergency or elective cardiac surgery. MATERIALS AND METHODS: This was a multicenter and descriptive study. Approval was granted by the Institutional Ethics Committee and informed consent for participation in the study was obtained from all the patients. The study included a total of 300 patients who underwent emergency or elective cardiovascular surgery and were then transferred to the ICU. Data were gathered from the demographic data form and the intensive care experience scale, which was developed by the researchers and applied through face to-face interviews with the patients. The independent-samples t-test, Mann Whitney U (Exact) test, one-way ANOVA (Robust Test: Brown-Forsythe), and multivariate analysis of variance were used in the analysis of the data. RESULTS: The study included 300 patients, comprising 108 (36%) females and 192 (64%) males. No difference was found between the groups in respect of total intensive care points of emergency (57.9 +/- 4.92) and elective (56.6 +/- 4.58) operations (P = 0.32). The environmental awareness level and patient satisfaction of the elective group were seen to be higher, and the emergency group reported more bad experiences. Patients who had undergone emergency cardiac valve surgery were more satisfied (P < 0.001) and remembered more (P = 0.001). CONCLUSION: Patients who had undergone urgent and elective cardiac surgery were seen to have had a relatively negative intensive care experience. When there was more environment awareness in patients with ICU experience, it was determined that as the duration of stay in the ICU lengthens out, the pessimistic experiences increased and ICU satisfaction decreases. PMID- 26856298 TI - Giant primary synovial sarcoma of the anterior mediastinum: A case report and review of literature. AB - Primary synovial sarcoma is a very rare tumor of the mediastinum, which is unreported in the entire subcontinent of West Africa, and presents daunting challenges from diagnosis to management with lack of standard management strategies. We present a case of primary monophasic synovial sarcoma of the anterior mediastinum, in a 22-year-old Nigerian lady who presented with cough, chest pain, and pleural effusion. Chest X-ray (CXR) and computed tomography on admission showed a left-sided huge mass in the left anterior mediastinum with no metastasis to the contralateral pleural cavity. Complete resection of the mediastinal tumor was done and histologic and immunohistochemical analyses confirmed a diagnosis of monophasic synovial sarcoma. However, 10 months postoperation she represented with chest pain, productive cough and a repeat CXR showed multiple left pulmonary nodules. She received two cycles of docetaxel and gemcitabine chemotherapy, but declined further treatment until her demise 8 months later. PMID- 26856299 TI - An unusual foreign body in the maxillary sinus: Dental impression material. AB - Foreign bodies in paranasal sinuses are very rare and most of them are encountered in the maxillary sinus. These foreign bodies may be organic or inorganic and can enter the maxillary sinus through an oro-antral fistula. The oro-antral fistula is formed by a break in the bony segment of the maxillary sinus floor and usually arises subsequent to maxillary premolar and molar extractions. A 63-year-old female patient evaluated for a nonhealing, left, toothless palate lesion and chronic headache occurring over 4 years. Radiography and computed tomography revealed bone discontinuity in the left floor of the maxillary sinus and calcifications within the antrum. A blue foreign body, later identified as dental impression material, was removed by intranasal endoscopy. A careful oral examination is recommended prior to prosthetic restorations. In addition, paranasal sinus foreign bodies should be surgically removed to prevent secondary soft tissue reactions. PMID- 26856300 TI - Isolated gallbladder rupture following blunt abdominal injury. AB - Isolated traumatic gallbladder rupture subsequent to blunt abdominal injury is rare. Most literatures on the subjects consist of case reports. We reported a rare case of isolated gallbladder rupture and discussed the possible predisposing factors to gallbladder rupture. PMID- 26856301 TI - Self-dispersible nanocrystals of albendazole produced by high pressure homogenization and spray-drying. AB - Albendazole (ABZ) is a broad-spectrum antiparasitic drug used in the treatment of human or animal infections. Although ABZ has shown a high efficacy for repeated doses in monogastric mammals, its low aqueous solubility leads to erratic bioavailability. The aim of this work was to optimize a procedure in order to obtain ABZ self-dispersible nanocrystals (SDNC) by combining high pressure homogenization (HPH) and spray-drying (SD). The material thus obtained was characterized and the variables affecting both the HPH and SD processes were studied. As expected, the homogenizing pressure and number of cycles influenced the final particle size, while the stabilizer concentration had a strong impact on SD output and redispersion of powders upon contact with water. ABZ SDNC were successfully obtained with high process yield and redispersibility. The characteristic peaks of ABZ were clearly identified in the X-ray patterns of the processed samples. A noticeable increase in the dissolution rate was observed in the aqueous environment. PMID- 26856302 TI - Plasma metabonomics study on toxicity biomarker in rats treated with Euphorbia fischeriana based on LC-MS. AB - Lang-du (LD) has been traditionally used to treat human diseases in China. Plasma metabolic profiling was applied in this study based on LC-MS to elucidate the toxicity in rats induced by injected ethanol extract of LD. LD injection was given by intraperitoneal injection at doses of 0.1, 0.05, 0.025 and 0 g kg(-1) body weight per day to rats. The blood biochemical levels of alanine aminotransferase, direct bilirubin, creatinine, serum beta2-microglobulin and low density lipoprotein increased in LD-injected rats, and the levels of total protein and albumin decreased in these groups. The metabolic profiles of the samples were analyzed by multivariate statistics analysis, including principal component analysis, partial least squares discriminant analysis and orthogonal projection to latent structures discriminate analysis (OPLS-DA). The metabolic characters in rats injected with LD were perturbed in a dose-dependent manner. By OPLS-DA, 18 metabolites were served as the potential toxicity biomarkers. Moreover, LD treatment resulted in an increase in the p-cresol, p-cresol sulfate, lysophosphatidylethanolamine (LPE) (18:0), LPE (16:0), lysophosphatidylcholine (16:0) and 12-HETE concentrations, and a decrease in hippuric acid, cholic acid and N-acetyl-l-phenylalanine. These results suggested that chronic exposure to LD could cause a disturbance in lipids metabolism and amino acids metabolism, etc. Therefore, an analysis of the metabolic profiles can contribute to a better understanding of the adverse effects of LD. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26856303 TI - Ultrasensitive terahertz modulation by silicon-grown MoS2 nanosheets. AB - Two-dimensional (2D) materials play more and more important roles these days, due to their broad applications in many areas. Herein, we propose an optically-pumped terahertz (THz) modulator, based on Si-grown MoS2 nanosheets. The broadband modulation effect has been proved by THz time domain spectroscopy and numerical simulation. The modulation depth of this Si-grown MoS2 nanosheet can reach over 75% under the low pumping power of 0.24 W cm(-2), much deeper than that of bare silicon. By theoretical models and simulation, it is proved that the broadband modulation effect can be described as a free carrier absorption for THz waves in the Drude form. Importantly, by a catalyst mechanism in the Si-grown MoS2, it is concluded that the MoS2-Si heterostructure enables the MoS2 to catalyze more carriers generated on the Si surface. This novel 2D material has a high effective modulation on THz waves under a low pumping power density, which affords it a promising potential in THz applications. PMID- 26856304 TI - The change of hippocampal volume and its relevance with inner ear function in Meniere's disease patients. AB - OBJECTIVES: To reveal the relationship between the disease progression and the hippocampal volume in Meniere's disease, which may indirectly reflect the degree of patients' chronic exposure to stress. METHODS: Retrospective review of medical records and brain magnetic resonance image (MRI) of Meniere's disease patients and healthy controls from 2008 to 2013. Age- and sex-matched consecutive 38 definite Meniere's disease patients and 76 healthy controls where brain MRIs, hearing, and vestibular function tests were available. We divided the patients into normal and abnormal groups according to the results functional tests such as pure tone audiometry (PTA), vestibular evoked myogenic potential (VEMP), and bithermal caloric test. RESULTS: Absolute hippocampal volume of Meniere's disease patients was significantly smaller than that of controls (3.33+/-0.84cm(3) for left side vs. 3.82+/-0.37cm(3) for right side, p<0.001). Mean left hippocampal volume of patients with abnormal VEMP and bithermal caloric test on lesion side was significantly smaller than that of the patients with the normal test result (all p<0.05). Average hearing thresholds of the patients showed strong correlation with left hippocampal volumes (p-value<0.001). Those with decreased left hippocampal volume were also more likely to experience augmented emotional stress reactivity. CONCLUSION: Meniere's disease patients had significantly decreased hippocampal volume and the volume was significantly correlated with severity of hearing and vestibular function of affected side. This may represent that Meniere's disease patients are exposed to chronic stress for unpredictable vertigo and hearing fluctuation, which finally cause hippocampus atrophy. PMID- 26856305 TI - A clinical review of 38 cases of cervical tuberculous lymphadenitis in Japan - The role of neck dissection. AB - OBJECTIVES: After tuberculous pleurisy, lymphadenitis arising from cervical lesion is the second most common form of extrapulmonary tuberculosis. It is generally treated with antituberculosis agents, but some patients resist chemotherapy. In such cases, surgical resection is often considered as an alternative treatment. This study aims to evaluate the therapeutic outcome of cervical tuberculous lymphadenitis and the future course of treatment of this disease. METHODS: We retrospectively reviewed the clinical charts of patients diagnosed at the Tokyo Metropolitan Tama Medical Center between 2009 and 2015 and identified 38 cases of cervical tuberculous lymphadenitis. Precisely 798 patients were registered for primary tuberculosis at our institution during the same period. RESULTS: Patient ages ranged from 21 to 85 years (average: 58.9 years), and the male-to-female ratio was 1:1.2. The range of tuberculosis progression was as follows: 30 (78.9%) in only the cervical lymph node, 3 in the other (axillary, mediastinal, and abdominal) lymph nodes, 1 in the lung and vertebrae lumbales, 2 in the lung, and 1 in the pleural membrane. All 38 patients were initially treated with antituberculous drugs at the Department of Pulmonary Medicine based on guidelines for tuberculosis cases in Japan. In seven cases, the antituberculous drugs were replaced due to side effects. Four cases involved a single drug-resistant strain, and one case involved a double drug-resistant strain. Thirty-three (86.8%) cases were cured by chemotherapy alone. The three patients resistant to chemotherapy were successfully treated through neck dissection. Thirty-six cases (94.7%) were cured by chemotherapy or chemotherapy and surgery. CONCLUSION: Local therapy could prove effective in cervical tuberculous lymphadenitis patients who exhibit an inadequate response to drugs. The role of neck dissection in cervical tuberculous lymphadenitis remains an important consideration. PMID- 26856306 TI - PPI in the PLEASANT trial: involving children with asthma and their parents in designing an intervention for a randomised controlled trial based within primary care. AB - : Aims We describe how patient and public involvement (PPI) was integrated into the design of an intervention for a randomised controlled trial (RCT) based within primary care. The RCT, known as the PLEASANT trial, aimed to reduce unscheduled medical contacts in children with asthma associated with start of the new school year in September with a simple postal intervention, highlighting the importance of maintaining asthma medication for helping to prevent increased asthma exacerbations. BACKGROUND: PPI is a key feature of UK health research policy, and is often a requirement of funding from the National Institute for Health Research. There are few detailed accounts of PPI in the design and conduct of clinical trials in the PPI literature for researchers to learn from. METHODS: We held PPI consultation events to determine whether the proposed intervention for the trial was acceptable to children with asthma and their parents, and to ascertain whether enhancements should be made. Two PPI consultation events were held with children with asthma and their parents, prior to the research commencing. Detailed field notes were taken by the research team at each consultation event. Findings At the first consultation event, parents and children endorsed the trial's rationale, made suggestions to the wording of the trial intervention letter, and made recommendations about to whom the letter should be sent out. At the second consultation event, parents discussed the timing of the intervention, commented on the lay summary of the Research Ethics Application, and were invited to join the trial's steering committee, while the children selected a logo for the study. PPI has resulted in enhancements to the PLEASANT study's intervention. A further PPI consultation event is scheduled for the end of the trial, in order for children with asthma and their parents to contribute to the trial's dissemination strategy. PMID- 26856307 TI - Telomere dysfunction and chromothripsis. AB - Chromothripsis is a recently discovered form of genomic instability, characterized by tens to hundreds of clustered DNA rearrangements resulting from a single dramatic event. Telomere dysfunction has been suggested to play a role in the initiation of this phenomenon, which occurs in a large number of tumor entities. Here, we show that telomere attrition can indeed lead to catastrophic genomic events, and that telomere patterns differ between cells analyzed before and after such genomic catastrophes. Telomere length and telomere stabilization mechanisms diverge between samples with and without chromothripsis in a given tumor subtype. Longitudinal analyses of the evolution of chromothriptic patterns identify either stable patterns between matched primary and relapsed tumors, or loss of the chromothriptic clone in the relapsed specimen. The absence of additional chromothriptic events occurring between the initial tumor and the relapsed tumor sample points to telomere stabilization after the initial chromothriptic event which prevents further shattering of the genome. PMID- 26856309 TI - Photothermally actuated interfacial hydration for fast friction switch on hydrophilic polymer brush modified PDMS sheet incorporated with Fe3O4 nanoparticles. AB - A near-infrared light triggered fast interfacial friction switch was achieved with polyelectrolyte brush grafted PDMS embedded with Fe3O4 nanoparticles, where the in situ heating up of the photothermal Fe3O4 nanoparticles in the polymer matrix changes the interface humidity and thereafter alters the hydration level of the interfacial polymer brushes. PMID- 26856308 TI - Combining S-cone and luminance signals adversely affects discrimination of objects within backgrounds. AB - The visual system processes objects embedded in complex scenes that vary in both luminance and colour. In such scenes, colour contributes to the segmentation of objects from backgrounds, but does it also affect perceptual organisation of object contours which are already defined by luminance signals, or are these processes unaffected by colour's presence? We investigated if luminance and chromatic signals comparably sustain processing of objects embedded in backgrounds, by varying contrast along the luminance dimension and along the two cone-opponent colour directions. In the first experiment thresholds for object/non-object discrimination of Gaborised shapes were obtained in the presence and absence of background clutter. Contrast of the component Gabors was modulated along single colour/luminance dimensions or co-modulated along multiple dimensions simultaneously. Background clutter elevated discrimination thresholds only for combined S-(L + M) and L + M signals. The second experiment replicated and extended this finding by demonstrating that the effect was dependent on the presence of relatively high S-(L + M) contrast. These results indicate that S-(L + M) signals impair spatial vision when combined with luminance. Since S-(L + M) signals are characterised by relatively large receptive fields, this is likely to be due to an increase in the size of the integration field over which contour defining information is summed. PMID- 26856311 TI - Summaries for Patients. Screening for Depression in Children and Adolescents: U.S. Preventive Services Task Force Recommendation Statement. PMID- 26856310 TI - Microbial colonization and lung function in adolescents with cystic fibrosis. AB - With intensified antibiotic therapy and longer survival, patients with cystic fibrosis (CF) are colonized with a more complex pattern of bacteria and fungi. However, the clinical relevance of these emerging pathogens for lung function remains poorly defined. The aim of this study was to assess the association of bacterial and fungal colonization patterns with lung function in adolescent patients with CF. Microbial colonization patterns and lung function parameters were assessed in 770 adolescent European (German/Austrian) CF patients in a retrospective study (median follow-up time: 10years). Colonization with Pseudomonas aeruginosa and MRSA were most strongly associated with loss of lung function, while mainly colonization with Haemophilus influenzae was associated with preserved lung function. Aspergillus fumigatus was the only species that was associated with an increased risk for infection with P. aeruginosa. Microbial interaction analysis revealed three distinct microbial clusters within the longitudinal course of CF lung disease. Collectively, this study identified potentially protective and harmful microbial colonization patterns in adolescent CF patients. Further studies in different patient cohorts are required to evaluate these microbial patterns and to assess their clinical relevance. PMID- 26856312 TI - The relationship between chronic obstructive pulmonary disease and transcatheter aortic valve implantation--A systematic review and meta-analysis. AB - OBJECTIVE: The present study was performed to investigate the relationship between chronic obstructive pulmonary disease (COPD) and transcatheter aortic valve implantation (TAVI). BACKGROUND: Controversies regarding the relationship between COPD and TAVI have intensified. METHODS: A literature review of the PubMed online database was performed, and articles published between January 1, 2002 and March 20, 2015 were analyzed. Random-effect and fixed-effect models were used, depending on the between-study heterogeneity. RESULTS: A total of 28 studies, involving 51,530 patients, were identified in our review. The burden of COPD ranged from 12.5% to 43.4%, and COPD negatively impacted both short-term and long-term all-cause survival (30 days: odds ratio [OR], 1.43, 95% CI, 1.14-1.79; >2 years: hazard ratio [HR], 1.34, 95% CI, 1.12-1.61). COPD was also associated with increased short-term and mid-term cardiac-cause mortality (30 days: OR, 1.29, 95% CI, 1.02-1.64; 1 year: HR: 1.09, 1.02-1.17). Moreover, COPD (OR, 1.97, 95% CI, 1.29-3.0) predicted post-TAVI acute kidney disease. Importantly, chronic kidney disease (CKD) (HR, 1.2, 95% CI, 1.1-1.32) and the distance of the 6 minute walk test (6MWT) (HR, 1.16, 1.06-1.27) predicted TAVI futility in patients with COPD. CONCLUSION: COPD is common among patients undergoing TAVI, and COPD impacts both short- and long-term survival. COPD patients, who had a lower BMI, shorter distance of 6MWT and CKD, were at higher risk for TAVI futility. PMID- 26856313 TI - Spectrofluorometric Determination of Putrescine Using Orthophthaldehyde as a Fluorophore: A Novel Method. AB - This paper concerns spectrofluorometric analysis of putrescine using orthophthaladehyde as a fluorophore in aqueous alkaline medium. Wavelengths of excitation and emission in acid, neutral, and alkaline media were different. There is a maximum intensity of fluorescence in alkaline medium 24 h after complexation compared with other media. Putrescine and orthophthaladehyde are used at an equimolar ratio, and the product is kinetically stable in alkaline medium. Calibration curves obtained gave limits of detection and quantification of 39 and 65 ng/mL, respectively. The correlation coefficient obtained in alkaline medium was 0.992 at pH 12. Results obtained largely showed a good reproducibility of our method. PMID- 26856314 TI - Influence of graft source and configuration on revision rate and patient-reported outcomes after MPFL reconstruction: a systematic review and meta-analysis. AB - PURPOSE: The purpose of this systematic review and meta-analysis was to determine the influence of graft source (allograft vs. autograft) and configuration (single limbed vs. double-limbed) on failure rate and disease-specific patient-reported outcome (Kujala score) after medial patellofemoral ligament (MPFL) reconstruction for patellar instability. METHODS: A systematic review of PubMed, Scopus, and the Cochrane Library was performed. A total of 31 studies met inclusion/exclusion criteria and were used to extract cohorts of patients who underwent ligament reconstruction with various allograft, autograft, single-limbed, and double limbed constructs. Failure rates and postoperative improvements in Kujala scores were compared between cohorts using inverse-variance weighting in a random effects analysis model and appropriate comparative statistical analyses (Chi squared and independent samples t tests). RESULTS: A total of 1065 MPFL reconstructions were identified in 31 studies. Autograft reconstructions were associated with greater postoperative improvements in Kujala scores when compared to allograft (32.2 vs. 22.5, p < 0.001), but there was no difference in recurrent instability (5.7 vs. 6.7 %, p = 0.74). Double-limbed reconstructions were associated with both improved postoperative Kujala scores (37.8 vs. 31.6, p < 0.001) and lower failure rate (10.6 vs. 5.5 %, p = 0.030). CONCLUSION: MPFL reconstructions should be performed using double-limbed graft configurations. While autograft tendon may be associated with higher patient-reported outcomes in the absence of associated connective tissue disorders or ligamentous laxity, patient factors and allograft processing techniques should be carefully considered when selecting an MPFL graft source, as revision rates were no different between graft sources. LEVEL OF EVIDENCE: IV. PMID- 26856316 TI - How to drill the talar tunnel in ATFL reconstruction? AB - PURPOSE: Reconstruction of the anterior talofibular ligament may be indicated in cases of residual instability after conservative treatment. Often, a bone tunnel is used for fixation in the talar bone. The purpose of this study is to evaluate possible routes for drilling the talar tunnel. METHODS: Virtual tunnels were generated in a 3D bone model, oriented towards the following external landmarks: the talar neck, the most anterior point of the medial malleolus (MM), the most distal point of the MM, the most medial point of the MM, and the most posterior point of the MM. The parameters analysed for tunnels with lengths of 20, 25, and 30 mm were the maximum distance inside the bone and the distance from the tunnel to the bone surface. A minimal safe distance (MSD) was calculated for a tunnel with a diameter of 5 mm. RESULTS: The shortest measured distance before arriving outside the talar bone was 16.7 mm. The longest distances were obtained in the tunnels oriented towards the talar neck (mean value of 36.6, SD 2.8) and towards the most posterior point of the MM (mean value of 35.8, SD 0.3). Only one tunnel, measuring 20 mm in depth and oriented towards the most posterior point of the MM, revealed no individual values below the MSD. CONCLUSION: External landmarks are useful for drilling a talar tunnel during reconstruction of the anterior talofibular ligament. Only one tunnel, oriented towards the most posterior point of the MM, measuring 5 mm in diameter and with a maximum depth of 20 mm, was safe in all individuals. Surgeons should be aware of these limits when treating patients with ankle instability. PMID- 26856315 TI - Surface electromyography and plantar pressure during walking in young adults with chronic ankle instability. AB - PURPOSE: Lateral ankle sprains are common and can manifest into chronic ankle instability (CAI) resulting in altered gait mechanics that may lead to subsequent ankle sprains. Our purpose was to simultaneously analyse muscle activation patterns and plantar pressure distribution during walking in young adults with and without CAI. METHODS: Seventeen CAI and 17 healthy subjects walked on a treadmill at 4.8 km/h. Plantar pressure measures (pressure-time integral, peak pressure, time to peak pressure, contact area, contact time) of the entire foot and nine specific foot regions and medial-lateral location of centre of pressure (COP) were measured. Surface electromyography (EMG) root mean square (RMS) amplitudes throughout the entire stride cycle and area under RMS curve for 100 ms pre-initial contact (IC) and 200 ms post-IC for anterior tibialis, peroneus longus, medial gastrocnemius, and gluteus medius were collected. RESULTS: The CAI group demonstrated a more lateral COP throughout the stance phase (P < 0.001 and Cohen's d > 0.9 for all 10 comparisons) and significantly increased peak pressure (P = 0.025) and pressure-time integral (P = 0.049) under the lateral forefoot. The CAI group had lower anterior tibialis RMS areas (P < 0.001) and significantly higher peroneus longus, medial gastrocnemius, and gluteus medius RMS areas during 100 ms pre-IC (P < 0.003). The CAI group had higher gluteus medius sEMG amplitudes during the final 50 % of stance and first 25% of swing (P < 0.05). CONCLUSIONS: The CAI group had large lateral deviations of their COP location throughout the entire stance phase and increased gluteus medius muscle activation amplitude during late stance through early swing phase. LEVEL OF EVIDENCE: III. PMID- 26856317 TI - Surgical management of isolated popliteus tendon injuries in paediatric patients. AB - Isolated popliteus avulsion injuries are a rare occurrence, especially in the skeletally immature population. Two cases of isolated popliteus tendon avulsion injuries in paediatric patients were identified and successfully managed with suture anchor reattachment of the avulsed fragment in the anatomic position. The objective of this case report is to raise awareness of orthopaedic surgeons to the rarely encountered isolated popliteus tendon injury that can occur in paediatric patients. Level of evidence Expert opinion, Level V. PMID- 26856318 TI - Constitutive expression of a novel antimicrobial protein, Hcm1, confers resistance to both Verticillium and Fusarium wilts in cotton. AB - Fusarium and Verticillium wilts, two of the most important diseases in cotton, pose serious threats to cotton production. Here we introduced a novel antimicrobial protein Hcm1, which comprised harpin protein from Xanthomonas oryzae pv. oryzicola (Xoc), and the chimeric protein, cecropin A-melittin, into cotton. The transgenic cotton lines with stable Hcm1 expression showed a higher resistance to Verticillium and Fusarium wilts both in greenhouse and field trials compared to controls. Hcm1 enabled the transgenic cotton to produced a microscopic hypersensitive response (micro-HR), reactive oxygen species (ROS) burst, and caused the activation of pathogenesis-related (PR) genes in response to biotic stress, indicating that the transgenic cotton was in a primed state and ready to protect the host from pathogenic infection. Simultaneously, Hcm1 protein inhibited the growth of Verticillium dahliae (V. dahliae) and Fusarium oxysporum (F. oxysporum) in vitro. The spread of fungal biomass was also inhibited in vivo since the V. dahliae biomass was decreased dramatically in transgenic cotton plants after inoculation with V. dahliae. Together, these results demonstrate that Hcm1 could activate innate immunity and inhibit the growth of V. dahliae and F. oxysporum to protect cotton against Verticillium and Fusarium wilts. PMID- 26856319 TI - Fluid consumption and taste novelty determines transcription temporal dynamics in the gustatory cortex. AB - BACKGROUND: Novel taste memories, critical for animal survival, are consolidated to form long term memories which are dependent on translation regulation in the gustatory cortex (GC) hours following acquisition. However, the role of transcription regulation in the process is unknown. RESULTS: Here, we report that transcription in the GC is necessary for taste learning in rats, and that drinking and its consequences, as well as the novel taste experience, affect transcription in the GC during taste memory consolidation. We show differential effects of learning on temporal dynamics in set of genes in the GC, including Arc/Arg3.1, known to regulate the homeostasis of excitatory synapses. CONCLUSIONS: We demonstrate that in taste learning, transcription programs were activated following the physiological responses (i.e., fluid consumption following a water restriction regime, reward, arousal of the animal, etc.) and the specific information about a given taste (i.e., taste novelty). Moreover, the cortical differential prolonged kinetics of mRNA following novel versus familiar taste learning may represent additional novelty related molecular response, where not only the total amount, but also the temporal dynamics of transcription is modulated by sensory experience of novel information. PMID- 26856320 TI - Effect of dexmedetomidine on hepatic ischemia-reperfusion injury in the setting of adult living donor liver transplantation. AB - OBJECTIVE: The aim of this study was to investigate the hypothesis that intraoperative infusion of dexmedetomidine can exert a protective effect against hepatic ischemia-reperfusion injury (IRI) in adult living donor liver transplantation (LDLiver transplantation). PATIENTS AND METHODS: Forty recipients were allocated into: control group (group I; n = 20) that received a placebo; and dexmedetomidine group (group II; n = 20) that received a continuous intraoperative infusion of 0.8 MUg/kg/h of dexmedetomidine. Data collected were AST, ALT, bilirubin, INR, and lactate, at baseline, immediately post-operatively, and on post-operative days 1, 3, and 5. Intercellular adhesion molecule-1 (ICAM 1) was measured at: baseline, 2 and 6 h after reperfusion, and on post-operative day 1. At the end of the surgery, a liver biopsy was sent for histopathological assessment. RESULTS: No significant difference was noticed in either group regarding MELD score, baseline AST, ALT, bilirubin, INR, or lactate. Dexmedetomidine tended to decrease blood pressure and heart rate, but the comparison was insignificant. Group II showed significantly attenuated levels of ICAM-1 and significantly minimal histopathological changes. The laboratory changes showed significantly lower AST, ALT, bilirubin, INR, and lactate in group II. CONCLUSIONS: Dexmedetomidine exerted protective effects against hepatic IRI during adult LDLiver transplantation, as indicated by suppression of ICAM-1, better scores of histopathological assessment, and augmented post-operative liver function tests. PMID- 26856321 TI - Comparing the unmatched count technique and direct self-report for sensitive health-risk behaviors in HIV+ adults. AB - Researchers often rely on self-report measures to assess sensitive health-risk behaviors in HIV+ individuals, yet the accuracy of self-report has been questioned, particularly when inquiring about behaviors that may be embarrassing, risky, and/or taboo. We compared an anonymous reporting method - the unmatched count technique (UCT) - to direct self-report (DSR) in order to assess reporting differences for several health-risk behaviors related to medication adherence and sexual risk. Contrary to hypotheses, the UCT only produced a significantly higher estimated base rate for one sensitive behavior: reporting medication adherence to one's physician, which may have been contextually primed by our study design. Our results suggest that anonymous reporting methods may not increase disclosure compared to DSR when assessing several health-risk behaviors in HIV+ research volunteers. However, our results also suggest that contextual factors should be considered and investigated further, as they may influence perception of sensitive behavior. PMID- 26856322 TI - n-3 Polyunsaturated Fatty Acids Improve Inflammation via Inhibiting Sphingosine Kinase 1 in a Rat Model of Parenteral Nutrition and CLP-Induced Sepsis. AB - The sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P) pathway plays a key role in inflammation. Parenteral nutrition containing n-3 polyunsaturated fatty acids (n-3 PUFA) may regulate inflammatory reactions. The aim of this study is to determine whether n-3 PUFA may improve inflammatory responses by neutralizing SphK1 signaling. Rat models of parenteral nutrition, cecal ligation and puncture (CLP)-induced sepsis were generated. Male Sprague-Dawley rats were operated for CLP on day 2 after venous catheterization. The rats were randomized to receive normal saline (NS; n = 20), parenteral nutrition (PN; n = 20), or PN + fish oil (FO; n = 20) for 5 days. The daily intake of fish oil (1.25-2.82 g EPA and 1.44-3.09 g DHA per 100 ml) in the FO group was approximately 1.8 g/kg body weight/day. Rats in the control group (n = 10) were subjected to sham operation and received a chow diet. Spleen tissues were collected for SphK1 and S1P receptor expression analysis. Our data showed that n-3 PUFA ameliorated the survival rate. SphK1 expression and its enzymatic activity were significantly upregulated in sepsis rats. Furthermore, mRNA and protein levels of S1PR3, but not S1PR1, were also facilitated after CLP. However, PN + FO dramatically decreased SphK1 mRNA level and its enzymatic activity. S1PR3 expression was also attenuated by FO addition. In conclusion, the anti-inflammatory effect of n-3 PUFA may be linked to the inhibition of the SphK1/S1P pathway in a rat model of parenteral nutrition and CLP-induced sepsis. PMID- 26856323 TI - The Child and Adolescent Needs and Strengths as an Outcome Measure in Community Mental Health: Factor Analysis and a Validation of the Short Form. AB - The goal of the study was to create a short-form measure based on the child and adolescent needs and strengths assessment tool. The measure was designed to be short and easy to use, relevant to youth treated in community-based mental health settings, useful for both treatment planning and program evaluation, and psychometrically valid. Factor analyses of the chosen items revealed two mental health factors and four functioning factors. The mental health factors included internalization and externalization, and the functioning factors included family, social, caregiver, and educational functioning. In support of validity, internalization and externalization subscales distinguished between clients diagnosed with internalizing and externalizing disorders and correlated with caregiver and self-report scores on the Youth Outcome Questionnaire. PMID- 26856325 TI - Abstracts of the 25th Annual Conference of APASL, February 20-24, 2016, Tokyo, Japan. PMID- 26856326 TI - Sorafenib combined with transarterial chemoembolization in patients with hepatocellular carcinoma: a meta-analysis and systematic review. AB - PURPOSE: Combination therapy of sorafenib and transarterial chemoembolization (TACE) has shown benefits in treating advanced hepatocellular carcinoma (HCC). This study evaluated the efficacy and safety of TACE + sorafenib. METHODS: MEDLINE, the Cochrane Library, EMBASE, and the ISI Web of Knowledge were searched (until 31 December 2013) for studies comparing TACE and TACE + sorafenib in treating patients with advanced HCC. Sensitivity and quality assessments were performed. RESULTS: Five comparative studies (2 were randomized control trials) that included 899 patients were used in the meta-analysis. Patients treated with TACE + sorafenib had better prognoses in terms of time to progression (TTP) compared to those with TACE + placebo or TACE alone; hazard ratios (HRs) ranged from 0.40 to 0.87, with the combined HR 0.61 (95 % CI 0.39-0.95, p = 0.031). However, the combined HR for overall survival (OS) did not differ significantly between patients treated with TACE + sorafenib and those with TACE + placebo or TACE alone (combined HR = 0.79, 95 % CI = 0.54-1.16, p = 0.235). Sensitivity analysis indicated the findings for TTP may be overly influenced by at least one of the studies. CONCLUSIONS: In summary, our meta-analysis found that TACE + sorafenib can improve TTP. We did not find the combined therapy improved OS. Additional randomized controlled studies are necessary to further investigate the clinical benefit of TACE + sorafenib in treating advanced HCC. PMID- 26856324 TI - Genome-wide association reveals QTL for growth, bone and in vivo carcass traits as assessed by computed tomography in Scottish Blackface lambs. AB - BACKGROUND: Improving meat quality including taste and tenderness is critical to the protection and development of markets for sheep meat. Phenotypic selection for such measures of meat quality is constrained by the fact that these parameters can only be measured post-slaughter. Carcass composition has an impact on meat quality and can be measured on live animals using advanced imaging technologies such as X-ray computed tomography (CT). Since carcass composition traits are heritable, they are potentially amenable to improvement through marker assisted and genomic selection. We conducted a genome-wide association study (GWAS) on about 600 Scottish Blackface lambs for which detailed carcass composition phenotypes, including bone, fat and muscle components, had been captured using CT and which were genotyped for ~40,000 single nucleotide polymorphisms (SNPs) using the Illumina OvineSNP50 chip. RESULTS: We confirmed that the carcass composition traits were heritable with moderate to high (0.19 0.78) heritabilities. The GWAS analyses revealed multiple SNPs and quantitative trait loci (QTL) that were associated with effects on carcass composition traits and were significant at the genome-wide level. In particular, we identified a region on ovine chromosome 6 (OAR6) associated with bone weight and bone area that harboured SNPs with p values of 5.55 * 10(-8) and 2.63 * 10(-9), respectively. The same region had effects on fat area, fat density, fat weight and muscle density. We identified plausible positional candidate genes for these OAR6 QTL. We also detected a SNP that reached the genome-wide significance threshold with a p value of 7.28 * 10(-7) and was associated with muscle density on OAR1. Using a regional heritability mapping approach, we also detected regions on OAR3 and 24 that reached genome-wide significance for bone density. CONCLUSIONS: We identified QTL on OAR1, 3, 24 and particularly on OAR6 that are associated with effects on muscle, fat and bone traits. Based on available evidence that indicates that these traits are genetically correlated with meat quality traits, these associated SNPs have potential applications in selective breeding for improved meat quality. Further research is required to determine whether the effects associated with the OAR6 QTL are caused by a single gene or several closely-linked genes. PMID- 26856327 TI - Evaluation of TgH(CX3CR1-EGFP) mice implanted with mCherry-GL261 cells as an in vivo model for morphometrical analysis of glioma-microglia interaction. AB - BACKGROUND: Glioblastoma multiforme is the most aggressive brain tumor. Microglia are prominent cells within glioma tissue and play important roles in tumor biology. This work presents an animal model designed for the study of microglial cell morphology in situ during gliomagenesis. It also allows a quantitative morphometrical analysis of microglial cells during their activation by glioma cells. METHODS: The animal model associates the following cell types: 1- mCherry red fluorescent GL261 glioma cells and; 2- EGFP fluorescent microglia, present in the TgH(CX3CR1-EGFP) mouse line. First, mCherry-GL261 glioma cells were implanted in the brain cortex of TgH(CX3CR1-EGFP) mice. Epifluorescence - and confocal laser-scanning microscopy were employed for analysis of fixed tissue sections, whereas two-photon laser-scanning microscopy (2P-LSM) was used to track tumor cells and microglia in the brain of living animals. RESULTS: Implanted mCherry GL261 cells successfully developed brain tumors. They mimic the aggressive behavior found in human disease, with a rapid increase in size and the presence of secondary tumors apart from the injection site. As tumor grows, mCherry-GL261 cells progressively lost their original shape, adopting a heterogeneous and diffuse morphology at 14-18 d. Soma size increased from 10-52 MUm. At this point, we focused on the kinetics of microglial access to glioma tissues. 2P-LSM revealed an intense microgliosis in brain areas already shortly after tumor implantation, i.e. at 30 min. By confocal microscopy, we found clusters of microglial cells around the tumor mass in the first 3 days. Then cells infiltrated the tumor area, where they remained during all the time points studied, from 6-18 days. Microglia in contact with glioma cells also present changes in cell morphology, from a ramified to an amoeboid shape. Cell bodies enlarged from 366 +/- 0.0 MUm(2), in quiescent microglia, to 1310 +/- 146.0 MUm(2), and the cell processes became shortened. CONCLUSIONS: The GL261/CX3CR1 mouse model reported here is a valuable tool for imaging of microglial cells during glioma growth, either in fixed tissue sections or living animals. Remarkable advantages are the use of immunocompetent animals and the simplified imaging method without the need of immunohistochemical procedures. PMID- 26856329 TI - The Asian tiger hunts in Maputo city--the first confirmed report of Aedes (Stegomyia) albopictus (Skuse, 1895) in Mozambique. AB - BACKGROUND: Increasing evidence suggests that dengue fever is endemic in Mozambique. Larvae of both the Afrotropical vector Aedes aegypti and its subspecies, Ae. aegypti formosus, have been reported from three provinces in Mozambique, two of which recently experienced dengue outbreaks. Despite reports of the invasive Oriental vector Ae. albopictus on the islands in the Mozambique Channel and nearby Indian Ocean, the species has not yet been reported in Mozambique. FINDINGS: Four host-seeking female mosquitoes, collected biting the authors in an urban neighbourhood of Maputo City in the late afternoon of 6 December, 2015, are herein morphologically confirmed as Ae. albopictus. CONCLUSION: This is the first report confirming the occurrence in Mozambique of Ae. albopictus, an invasive species and an important vector of human arboviruses. In view of its potential role as a vector of dengue, Chikungunya and Zika viruses, studies are urgently needed to assess the geographical expansion and relative abundance of these important vectors to better understand the potential transmission impact of arboviruses that are efficiently transmitted and globally spread by these vectors. PMID- 26856330 TI - The long non-coding RNA TUG1 indicates a poor prognosis for colorectal cancer and promotes metastasis by affecting epithelial-mesenchymal transition. AB - BACKGROUND: Long intergenic non-coding RNAs (lncRNAs) are a class of non-coding RNAs that are involved in gene expression regulation. Taurine up-regulated gene 1 (TUG1) is a cancer progression related lncRNA in some tumor oncogenesis; however, its role in colorectal cancer (CRC) remains unclear. In this study, we determined the expression patterns of TUG1 in CRC patients and explored its effect on CRC cell metastasis using cultured representative CRC cell lines. METHODS: The expression levels of TUG1 in 120 CRC patients and CRC cells were determined using quantitative real-time PCR. HDACs and epithelial-mesenchymal transition (EMT) related gene expression were determined using western blot. CRC cell metastasis was assessed by colony formation, migration assay and invasion assay. RESULTS: Our data showed that the levels of TUG1 were upregulated in both CRC cell lines and primary CRC clinical samples. TUG1 upregulation was closely correlated with the survival time of CRC patients. Overexpression of TUG1 in CRC cells increased their colony formation, migration, and invasion in vitro and promoted their metastatic potential in vivo, whereas knockdown of TUG1 inhibited the colony formation, migration, and invasion of CRC cells in vitro. It is also worth pointing out that TUG1 activated EMT-related gene expression. CONCLUSION: Our data suggest that tumor expression of lncRNA TUG1 plays a critical role in CRC metastasis. TUG1 may have potential roles as a biomarker and/or a therapeutic target in colorectal cancer. PMID- 26856328 TI - SNARE complex in developmental psychiatry: neurotransmitter exocytosis and beyond. AB - Multiple biological processes throughout development require intracellular vesicular trafficking, where the SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (SNAP) receptors) complex plays a major role. The core proteins forming the SNARE complex are SNAP-25 (synaptosomal-associated protein 25), VAMP (vesicle-associated membrane protein) and Syntaxins, besides its regulatory proteins, such as Synaptotagmin. Genes encoding these proteins (SNAP25, VAMP1, VAMP2, STX1A, SYT1 and SYT2) have been studied in relation to psychiatric disorders susceptibility. Here, we review physiological aspects of SNARE complex and genetic association results reported for attention deficit hyperactivity disorder, both in children and adults, autism spectrum disorders, major depressive disorder, bipolar disorder and schizophrenia. Moreover, we included findings from expression, pharmacogenetics and animal model studies regarding these clinical phenotypes. The overall scenario depicted here suggests that the SNARE complex may exert distinct roles throughout development, with age specific effects of genetic variants in psychiatric disorders. Such perspective should be considered in future studies regarding SNARE complex genes. PMID- 26856332 TI - Optimizing sample preparation for anatomical determination in the hippocampus of rodent brain by ToF-SIMS analysis. AB - Lipidomics has been an expanding field since researchers began to recognize the signaling functions of lipids and their involvement in disease. Time-of-flight secondary ion mass spectrometry is a valuable tool for studying the distribution of a wide range of lipids in multiple brain regions, but in order to make valuable scientific contributions, one has to be aware of the influence that sample treatment can have on the results. In this article, the authors discuss different sample treatment protocols for rodent brain sections focusing on signal from the hippocampus and surrounding areas. The authors compare frozen hydrated analysis to freeze drying, which is the standard in most research facilities, and reactive vapor exposure (trifluoroacetic acid and NH3). The results show that in order to preserve brain chemistry close to a native state, frozen hydrated analysis is the most suitable, but execution can be difficult. Freeze drying is prone to produce artifacts as cholesterol migrates to surface, masking other signals. This effect can be partially reversed by exposing freeze dried sections to reactive vapor. When analyzing brain sections in negative ion mode, exposing those sections to NH3 vapor can re-establish the diversity in lipid signal found in frozen hydrated analyzed sections. This is accomplished by removing cholesterol and uncovering sulfatide signals, allowing more anatomical regions to be visualized. PMID- 26856331 TI - Immunopotentiation of four natural adjuvants co-administered with a highly pathogenic porcine reproductive and respiratory syndrome virus glycoprotein 5 subunit. AB - To improve the efficacy of porcine reproductive and respiratory syndrome virus (PRRSV) subunit vaccine, the immunological enhancement effects of four natural adjuvants were compared, including Astragalus extract, Astragalus/Bacillus production, propolis, and Freund's adjuvant. The results showed that titers of IgG and neutralizing antibody against highly pathogenic PRRSV (HP-PRRSV) glycoprotein 5 (GP5) from the groups of Astragalus/Bacillus adjuvant and Freund's adjuvant co-administered with a recombinant HP-PRRSV GP5 subunit were the highest among all the experimental groups. In cellular immunity, as shown in T lymphocyte proliferation level, Astragalus/Bacillus adjuvant and Freund's adjuvant exhibited the most potent immunological enhancement effects. Exceptionally, pigs inoculated with Freund's adjuvant developed severely delayed humoral immune responses within 28 days post inoculation. The adjuvants of Astragalus extract and propolis also exhibited immunological enhancement effects on humoral immune and cell-mediated immune responses, but which were obviously lower than Astragalus/Bacillus adjuvant and Freund's adjuvant. Following challenge with HP-PRRSV, pigs inoculated with Astragalus/Bacillus adjuvant and Freund's adjuvant co administered with GP5 subunit showed lower viremia, slighter clinical signs, and less pathological lung lesions compared with the groups inoculated using Astragalus extract and propolis. In conclusion, from immune responses and immunological protection against HP-PRRSV, the Astragalus/Bacillus adjuvant demonstrated the most potent immunological enhancement effect on HP-PRRSV GP5 subunit. Astragalus/Bacillus adjuvant showed promise as a candidate immune adjuvant, to more efficiently prevent and control PRRS. PMID- 26856333 TI - Reduce the matrix effect in biological tissue imaging using dynamic reactive ionization and gas cluster ion beams. AB - In the context of a secondary ion mass spectrometry (SIMS) experiment, dynamic reactive ionization (DRI) involves introducing a reactive dopant, HCl, into an Ar gas cluster primary ion beam along with a source of water to enable dissociation of HCl to free protons. This concerted effect, precisely occurring at the impact site of the cluster beam, enhances the protonation of molecular species. Here, the authors apply this methodology to study the hippocampus and cerebellum region of a frozen-hydrated mouse brain section. To determine the degree of enhancement associated with DRI conditions, sequential tissue slices were arranged in a mirrored configuration so that comparable regions of the tissue could be explored. The results show that the protonated lipid species are increased by ~10 fold, but that the normally prevalent salt adducts are virtually unaffected. This observation is discussed as a novel approach to minimizing SIMS matrix effects in complex materials. Moreover, the chemical images of protonated lipid ions exhibit clearer features in the cerebellum region as compared to images acquired with the pure Ar cluster beam. PMID- 26856334 TI - TGF-beta signaling is activated in patients with chronic HBV infection and repressed by SMAD7 overexpression after successful antiviral treatment. AB - OBJECTIVES: Although animal studies demonstrated that Smad7 induction ameliorates TGF-beta/SMAD-mediated fibrogenesis, its role in human hepatic diseases is rather obscure. Our study explored the activation status of TGF-beta/activin pathway in patients with chronic liver diseases, and how it is affected by successful antiviral treatment in chronic HBV hepatitis (CHB). METHODS: Thirty-seven CHB patients (19 with active disease, 14 completely remitted on long-term antiviral treatment and 4 with relapse after treatment withdrawal), 18 patients with chronic HCV hepatitis, 12 with non-alcoholic fatty liver disease (NAFLD), and 3 controls were enrolled in the study. Liver mRNA levels of CTGF, all TGF beta/activin isoforms, their receptors and intracellular mediators (SMADs) were evaluated using qRT-PCR and were correlated with the grade of liver inflammation and fibrosis staging. The expression and localization of pSMAD2 and pSMAD3 were assessed by immunohistochemistry. RESULTS: TGF-beta signalling is activated in CHB patients with active disease, while SMAD7 is up-regulated during the resolution of inflammation after successful treatment. SMAD7 overexpression was also observed in NAFLD patients exhibiting no or minimal fibrosis, despite the activation of TGF-beta/activin signaling. CONCLUSIONS: SMAD7 overexpression might represent a mechanism limiting TGF-beta-mediated fibrogenesis in human hepatic diseases; therefore, SMAD7 induction likely represents a candidate for novel therapeutic approaches. PMID- 26856335 TI - The rat closely mimics oxidative stress and inflammation in humans after exercise but not after exercise combined with vitamin C administration. AB - PURPOSE: The purpose of the present study was to directly compare oxidative stress and inflammation responses between rats and humans. METHODS: We contrasted rat and human oxidative stress and inflammatory responses to exercise (pro oxidant stimulus) and/or vitamin C (anti-oxidant stimulus) administration. Vitamin C was administered orally in both species (16 mg kg(-1) of body weight). Twelve redox biomarkers and seven inflammatory biomarkers were determined in plasma and erythrocytes pre- and post-exercise or pre- and post-exercise combined with vitamin C administration. RESULTS: Exercise increased oxidative stress and induced an inflammatory state in rats and humans. There were only 1/19 significant species * exercise interactions (catalase), indicating similar responses to exercise between rats and humans in redox and inflammatory biomarkers. Vitamin C decreased oxidative stress and increased antioxidant capacity only in humans and did not affect the redox state of rats. In contrast, vitamin C induced an anti-inflammatory state only in rats and did not affect the inflammatory state of humans. There were 10/19 significant species * vitamin C interactions, indicating that rats poorly mimic human oxidative stress and inflammatory responses to vitamin C administration. Exercise after acute vitamin C administration altered redox state only in humans and did not affect the redox state of rats. On the contrary, inflammation biomarkers changed similarly after exercise combined with vitamin C in both rats and humans. CONCLUSIONS: The rat adequately mimics human responses to exercise in basic blood redox/inflammatory profile, yet this is not the case after exercise combined with vitamin C administration. PMID- 26856336 TI - Erratum to: Effects of Three Types of Exercise Interventions on Healthy Old Adults' Gait Speed: A Systematic Review and Meta-Analysis. PMID- 26856337 TI - Erratum to: Dose-Response Relationships of Balance Training in Healthy Young Adults: A Systematic Review and Meta-Analysis. PMID- 26856338 TI - Effects of Exercise on Bone Status in Female Subjects, from Young Girls to Postmenopausal Women: An Overview of Systematic Reviews and Meta-Analyses. AB - BACKGROUND: Osteoporosis and postmenopausal bone loss pose a huge social and economic burden worldwide. Regular exercise and physical activity are effective interventions for maximizing or maintaining peak bone mass and preventing bone loss in the elderly; however, most recommendations are addressed to the general public and lack specific indications for girls and women, the segment of the population most at risk for developing osteoporosis. OBJECTIVE: The aim of this overview of systematic reviews and meta-analyses was to summarize current evidence for the effects of exercise and physical activity interventions on bone status in girls and women, and to explore whether specific exercise programs exist for improving or maintaining bone mass or bone strength in females. METHODS: The PubMed, EMBASE, PEDro, and Cochrane Library databases were searched from January 2009, updated to 22 June 2015, using the following groups of search terms: (i) 'physical activity' and 'exercise'; and (ii) 'bone', 'bone health', 'bone strength', 'bone structure', 'bone metabolism', 'bone turnover', and 'bone biomarkers'. Searches and screening were limited to systematic reviews or meta analyses of studies in females and published in English. Our final analysis included 12 articles that met the inclusion criteria. RESULTS: Combined-impact exercise protocols (impact exercise with resistance training) are the best choice to preserve/improve bone mineral density in pre- and postmenopausal women. Peak bone mass in young girls can be improved with short bouts of school-based high impact plyometric exercise programs. Whole-body vibration exercises have no beneficial effects on bone in postmenopausal or elderly women. CONCLUSIONS AND IMPLICATIONS: Lifelong exercise, specific for age, is an effective way to sustain bone health in girls and women. PMID- 26856339 TI - Neuromuscular Risk Factors for Knee and Ankle Ligament Injuries in Male Youth Soccer Players. AB - Injuries reported in male youth soccer players most commonly occur in the lower extremities, and include a high proportion of ligament sprains at the ankle and knee with a lower proportion of overuse injuries. There is currently a paucity of available literature that examines age- and sex-specific injury risk factors for such injuries within youth soccer players. Epidemiological data have reported movements that lead to non-contact ligament injury include running, twisting and turning, over-reaching and landing. Altered neuromuscular control during these actions has been suggested as a key mechanism in females and adult populations; however, data available in male soccer players is sparse. The focus of this article is to review the available literature and elucidate prevalent risk factors pertaining to male youth soccer players which may contribute to their relative risk of injury. PMID- 26856340 TI - Ce (III) - Porphyrin Sandwich Complex Ce2(TPP)3: A Rod-Like Nanoparticle as a Fluorescence Turn-Off Probe for Detection of Hg (II) and Cu (II). AB - In this study the researcher reports a novel, one step synthesized rod-like nanoparticles of cerium (III)-tetraphenylporphyrin sandwich complex as a spectrofluorometric sensor to measure trace amount of Hg (II) and Cu (II) metal ions. Moreover, the synthesized fluorescent probe was able to detect higher amounts (>10(-4) M) of Hg (II) in aqueous media by changing the color which can also be used as a selective mercury naked-eye sensor. The selectivity and sensitivity of the sensor based on its fluorescence quenching in the presence of Hg (II) and Cu (II) were studied according to the Stern-Volmer equation. The detection limit of the sensor was 16 nM for Hg (II) and about 2.34 MUM for Cu (II) ions. Graphical Abstract Ce2(TPP)3 sandwich complex application as a fluorescent probe for measuring trace amounts of mercury and copper in real samples. PMID- 26856341 TI - Effects of Structure and Environment on the Spectroscopic Properties of (3-Amino Substituted-Thieno[2,3-b] Pyridine-2-yl)Pyridine/Quinolin-2 yl)(Phenyl)Methanones: Experimental and Theoretical Study. AB - The electronic absorption, excitation and fluorescence properties of two 3-amino substituted-thieno[2,3-b]pyridine/quinolin-2-yl)(phenyl)methanones; (referred to as compounds 1-2: where 3-amino-4,5,6-trimethyl-thieno[2,3-b]pyridin-2 yl)(phenyl)methanone (1); and 3-amino-5,6,7,8-tetrahydro-thieno[2,3-b]quinolin-2 yl)(phenyl)methanone (2)) have been investigated in solvents of various polarity and hydrogen-bonding abilities. Results based on the electronic absorption, excitation and emission study of these compounds; indicated that singlets (S1 and S2) excited-states are populated in non-polar and polar protic/aprotic solvents giving dual fluorescence with weak charge transfer separation. The experimental results were interpreted with the aid of quantum chemistry calculations carried out with the DFT and TD-DFT/B3lyp/6-31 + G(d,p) methods. Based on these calculations, compounds 1-2 exist in two rotamers: anti and syn, separated by ca. 5-6 kcal mol(-1) energy barriers in favor of the anti-conformer. The anti structure, was shown to be stabilized through existence of intramolecular NH...O hydrogen bond (H-b), which plays a dominant role in affecting the energy of the HOMO-1 molecular orbital. Further, methyl/alkyl substitution in the pyridyl thiophene ring was shown to involve in sigma-pi hyper-conjugation and destabilization of the HOMO-1 MO's. PMID- 26856342 TI - Acinetobacter baumannii virulence determinants involved in biofilm growth and adherence to host epithelial cells. PMID- 26856343 TI - Third molar impaction and agenesis: influence on anterior crowding. AB - Background Third molar influence on anterior crowding is controversial, but they are assumed to play a major role in compromising dental arch space. Aim To evaluate the relationship among impaction, agenesis and crowding in black South African males. Subjects and method Mandibles and maxillae of 535 black South African males in the Raymond A. Dart Collection of Human Skeletons, University of the Witwatersrand were examined for anterior crowding and third molar agenesis and impaction. Dental crowding was determined using Little's irregularity index. Results Individuals with impaction showed more moderate-to-extreme crowding than those with agenesis. Bilateral third molar presence was more frequently associated with ideal-to-minimal crowding. Weak positive but significant correlations between crowding and impaction were found (mandible, rho = 0.154, p = 0.000; maxilla rho = 0.130, p = 0.000). The direction was the opposite for bilateral presence of molars (mandible, rho = -0.135, p = 0.02; maxilla, rho = 0.111, p = 0.010). Odds of mandibular crowding were greatest in individuals with impaction (OR = 3.22, CI = 1.716-6.05, p < 0.001). Maxillary results were similar. Conclusion Third molar impaction plays a role in anterior crowding. Third molar presence was not associated with anterior crowding, while agenesis did not explain absence of crowding. PMID- 26856344 TI - Effect of acute intermittent hypoxia on motor function in individuals with chronic spinal cord injury following ibuprofen pretreatment: A pilot study. AB - INTRODUCTION: Acute intermittent hypoxia (AIH) enhances lower extremity motor function in humans with chronic incomplete spinal cord injury (SCI). AIH-induced spinal plasticity is inhibited by systemic inflammation in animal models. Since SCI is frequently associated with systemic inflammation in humans, we tested the hypothesis that pretreatment with the anti-inflammatory agent ibuprofen enhances the effects of AIH. METHODS: A randomized, double-blinded, placebo-controlled crossover design was used. Nine adults (mean age 51.1 +/- 13.1 years) with chronic motor-incomplete SCI (7.7 +/- 6.3 years post-injury) received a single dose of ibuprofen (800 mg) or placebo, 90 minutes prior to AIH. For AIH, 9% O2 for 90 seconds was interspersed with 21% O2 for 60 seconds. Maximal voluntary ankle plantar flexion isometric torque was assessed prior to, and at 0, 30, and 60 minutes post-AIH. Surface electromyography (EMG) of plantar flexor muscles was also recorded. RESULTS: Torque increased significantly after AIH at 30 (P = 0.007; by ~20%) and 60 (P < 0.001; by ~30%) minutes post-AIH versus baseline. Ibuprofen did not augment the effects of AIH. EMG activity did not increase significantly after AIH; however, there was a significant association between increases in torque and EMG in both gastrocnemius (R2 = 0.17, P < 0.005) and soleus (R2 = 0.17, P < 0.005) muscles. CONCLUSIONS: AIH systematically increased lower extremity torque in individuals with chronic incomplete SCI, but there was no significant effect of ibuprofen pretreatment. Our study re-confirms the ability of AIH to enhance leg strength in persons with chronic incomplete SCI. PMID- 26856345 TI - Mechanism of Action and Pharmacology of Patiromer, a Nonabsorbed Cross-Linked Polymer That Lowers Serum Potassium Concentration in Patients With Hyperkalemia. AB - Hyperkalemia is a potentially life-threatening condition, and patients who have chronic kidney disease, who are diabetic, or who are taking renin-angiotensin aldosterone system inhibitors are at increased risk. Therapeutic options for hyperkalemia tend to have limited effectiveness and can be associated with serious side effects. Colonic potassium secretion can increase to compensate when urinary potassium excretion decreases in patients with renal impairment, but this adaptation is insufficient and hyperkalemia still results. Patiromer is a novel, spherical, nonabsorbed polymer designed to bind and remove potassium, primarily in the colon, thereby decreasing serum potassium in patients with hyperkalemia. Patiromer has been found to decrease serum potassium in patients with hyperkalemia having chronic kidney disease who were on renin-angiotensin aldosterone system inhibitors. Results of nonclinical studies and an early phase clinical study are reported here. Two studies with radiolabeled drug, one in rats and the other in dogs, confirmed that patiromer was not absorbed into the systemic circulation. Results of an in vitro study showed that patiromer was able to bind 8.5 to 8.8 mEq of potassium per gram of polymer at a pH similar to that found in the colon and had a much higher potassium-binding capacity compared with other resins, including polystyrene sulfonate. In a study in hyperkalemic rats, a decrease in serum potassium was observed via an increase in fecal potassium excretion. In a clinical study in healthy adult volunteers, a significant increase in fecal potassium excretion and a significant decrease in urinary potassium excretion were observed. Overall, patiromer is a high-capacity potassium binder, and the chemical and physical characteristics of patiromer may lead to good clinical efficacy, tolerability, and patient acceptance. PMID- 26856347 TI - Open-Source, Web-Based Dashboard Components for DICOM Connectivity. AB - The administration of a DICOM network within an imaging healthcare institution requires tools that allow for monitoring of connectivity and availability for adequate uptime measurements and help guide technology management strategies. We present the implementation of an open-source widget for the Dashing framework that provides basic dashboard functionality allowing for monitoring of a DICOM network using network "ping" and DICOM "C-ECHO" operations. PMID- 26856346 TI - The Ontogeny and Population Variability of Human Hepatic NADPH Dehydrogenase Quinone Oxido-Reductase 1 (NQO1). AB - The NADPH dehydrogenase quinone oxido-reductase 1 (NQO1) enzyme is an antioxidant and metabolic enzyme that performs two electron reduction of quinones and other chemicals. Based on the physiologic role(s) of NQO1, we hypothesized that expression and activity of this enzyme would vary with age and other demographic variables. Cytosols from 117 archived human livers were investigated for changes in NQO1 with age, sex, obesity, and ethnicity. Protein expression but not activity of NQO1 was weakly negatively correlated with age (Spearman r = -0.2, P = 0.03). No sex differences were observed for either protein expression or activity and for ethnicity; Caucasians had greater NQO1 activity than Asians (P < 0.05). Overweight children had statistically significantly higher NQO1 activity as compared with ideal weight children (P < 0.05) although this difference was not observed in adults. These findings establish that NQO1 is approximately as active in children as adults. However, modeled NQO1 clearance (both allometric and physiologically based pharmacokinetics) predicted maturation at 23 to 26 years. This is almost certainly an overestimate, with error in the model resulting from a small sample size and inability to scale for age-related changes in hepatic cellularity and/or cytosolic protein content, and indicates a delay in reaching maximum clearance through the NQO1 pathway that is affected by physiologic development as much, or more than, biochemical development. Obesity may increase hepatic NQO1 activity in children, which is likely a protective mechanism in oxidative stress, but may also have significant implications for drug and chemical disposition in obese children. PMID- 26856348 TI - PORTER: a Prototype System for Patient-Oriented Radiology Reporting. AB - To empower patients to participate in their medical care and decision-making, effective communication is critical. In radiology, the clinical report is the primary medium of communication. Although radiologists historically have authored reports with the referring provider as the intended reader, patients increasingly access the reports through portals to electronic health record systems. We developed a system named PORTER (Patient-Oriented Radiology Reporter) to augment radiology reports with lay-language definitions. Our IRB-approved, HIPAA compliant study protocol analyzed 100 knee MRI reports from an academic medical center to identify the most commonly utilized terms. A glossary of 313 terms was constructed to include definitions of the terms and, where available, links to reference sources and public-domain images. Flesch-Kincaid readability scores were computed to assure that definitions were readable at or below 10th-grade reading level. The system provided an interactive web site to view outpatient knee MRI exams. After logging in with their exam ID number and date of birth, patients viewed their report annotated with definitions from the glossary. Applicable images were displayed when the user's mouse hovered over a glossary term. This patient-oriented system can help empower patients to better understand their radiology results. PMID- 26856349 TI - Outcomes in Cardiac Arrest Patients due to Toxic Exposure Treated with Therapeutic Hypothermia. AB - The incidence and outcome of patients who undergo therapeutic hypothermia (TH) after toxin-induced cardiac arrest (TICA) is not previously described. Our study aimed to describe the incidence, epidemiologic characteristics, and outcomes of patients who experience TICA in a dedicated clinical pathway for post-cardiac arrest care between November 2007 and February 2013. All patients were treated in an evidence-based clinical pathway that included TH. Database and medical records were independently reviewed by investigators to ascertain TICA. TICA was defined as cardiac arrest (CA) directly and immediately caused by a xenobiotic exposure. All patients were enrolled at Carolinas Medical Center, an urban 874-bed teaching hospital that serves as a regional cardiac resuscitation center. All patients were adult victims of cardiac arrest who had obtained return of spontaneous circulation and were enrolled in a clinical pathway for post-cardiac arrest care that included TH. Three hundred eighty-nine patients underwent treatment following CA during the study period and 48 (12 %) were deemed TICA. Patients who suffered TICA were slightly younger, less likely to have an initial shockable rhythm, and less likely to receive bystander CPR as compared to non-toxic cases. TICA accounted for a significant proportion of patients in this study. Additional, larger studies are needed to fully elucidate the optimal role for TH in TICA. PMID- 26856350 TI - Acute on Chronic Ivabradine Overdose: a Case Report. AB - Ivabradine is a newly approved medication which reduces the heart rate by antagonizing the If channel. We report a case of intentional overdose on ivabradine. A 26-year-old female presented after taking 250 mg ivabradine. On arrival, her vital signs and neurologic exam were unremarkable. Within 30 min, her heart rate decreased to 31 bpm, but she remained normotensive with no change in mentation. Her bradycardia resolved after treatment with atropine. She experienced two further bradycardic episodes responsive to atropine; the second episode was associated with hypotension, responsive to a fluid bolus. For the remainder of her hospitalization, she remained hemodynamically stable without further interventions. She was dispositioned to the psychiatry service approximately 36 h post-ingestion with a heart rate of 67 bpm. Laboratory analysis confirmed a serum ivabradine concentration of 525 ng/mL, greater than 50 times the mean level in therapeutic trials. Proposed treatments for ivabradine include activated charcoal, atropine, isoproterenol, and intravenous pacing. Further study is needed to identify ideal treatment modalities. PMID- 26856352 TI - Margaret McCartney: Why GPs are stressed. PMID- 26856351 TI - Two Cases of Refractory Cardiogenic Shock Secondary to Bupropion Successfully Treated with Veno-Arterial Extracorporeal Membrane Oxygenation. AB - Bupropion inhibits the uptake of dopamine and norepinephrine. Clinical effects in overdose include seizure, status epilepticus, tachycardia, arrhythmias, and cardiogenic shock. We report two cases of severe bupropion toxicity resulting in refractory cardiogenic shock, cardiac arrest, and repeated seizures treated successfully. Patients with cardiovascular failure related to poisoning may particularly benefit from extracorporeal membrane oxygenation (ECMO). These are the first cases of bupropion toxicity treated with veno-arterial EMCO (VA-ECMO) in which bupropion toxicity is supported by confirmatory testing. Both cases demonstrate the effectiveness of VA-ECMO in poisoned patients with severe cardiogenic shock or cardiopulmonary failure. PMID- 26856353 TI - Corrigendum for: ICE1 of Poncirus trifoliata functions in cold tolerance by modulating polyamine levels by interacting with arginine decarboxylase. PMID- 26856354 TI - Maternal and fetal outcome in women with antiphospholipid syndrome: a three-year observational study. AB - OBJECTIVES: To assess prospectively the maternal and fetal outcome in women with primary antiphospholipid syndrome (APS) and to find out predictors of poor obstetric outcome. METHODS: A prospective observational study included 162 patients with primary APS who were divided into two groups, group 1 with previous thrombosis (n = 74) and group 2 without previous thrombosis (n = 88). Patients were followed from the start of pregnancy till delivery under standard treatment to detect maternal and fetal outcome. RESULTS: There was a significant difference between the two groups with higher rate of miscarriage (p < 0.05), maternal venous thromboembolism (p < 0.001), intrauterine fetal demise and neonatal death (p < 0.05) in group 1. No significant difference between the two groups regarding the rate of preeclampsia, eclampsia, postpartum hemorrhage, prematurity and admission to neonatal intensive care unit (p > 0.05). By univariate and multivariate analyzes in the whole study participants, previous thrombosis, triple positivity of APS antibodies, previous delivery before 34 weeks, the presence of antibeta2GP1 antibodies and maternal age above 30 years were independent predictors of pregnancy loss. CONCLUSION: Poor obstetric outcome is higher in patients with previous thrombosis. The search for optimal prognostic markers and new therapeutic measures to prevent complications in APS patients is warranted. PMID- 26856355 TI - Empathy and affect: what can empathied bodies do? AB - While there has been much interest in the apparent benefits of empathy in improving outcomes of medical care, there is continuing concern over the philosophical nature of empathy. We suggest that part of the difficulty in coming to terms with empathy is due to the modernist dichotomies that have structured Western medical discourse, such that doctor and patient, knower and known, cognitive and emotional, subject and object are situated in oppositional terms, with the result that such accounts cannot coherently encompass an emotional doctor, or a patient as knower, or empathy as other than a possession or a trait. This paper explores what, by contrast, a radical critique of the Cartesian world view, in the form of a Deleuzean theoretical framework, would open up in new perspectives on empathy. We extend the framework of emotional geography to ask what happens when people are affected by empathy. We suggest that doctors and patients might be more productively understood as embodied subjects that are configured in their capacities by how they are affected by singular 'events' of empathy. We sketch out how the Deleuzean framework would make sense of these contentions and identify some possible implications for medical education and practice. PMID- 26856356 TI - Gastroenvironmental distress: metaphorical antecedents of the gut microbiome. AB - The human gut has been viewed for centuries as a potential mediator of systemic disease. The theory of autointoxication, which found its clearest articulation in the late nineteenth and early twentieth centuries, focused on altered bowel habits as the cause of widespread physical decay and advocated for the pursuit of health through regular defecation. More recently, under the banner of the microbiome, research on commensal bacteria makes a similar case for associations between alimentary dynamics and illness manifestations far outside the gastrointestinal tract. Surface distinctions between these two conceptual frameworks are apparently antipodal, the former championing emptiness and sterility, the latter abundance and restoration. Within both models, however, persists a common anxiety about the detrimental effects of civilisation on the body in relation to the natural world. As scientific understanding of the microbiome continues to mature, acknowledging the historical and moral parameters of its borrowed ecological idiom may facilitate critical distinctions between what is true and what feels like it should be. PMID- 26856357 TI - Intracranial spread of IgG4-related disease via skull base foramina. AB - IgG4-related disease (IgG4-RD) is a newly recognised, multiorgan, inflammatory disease, and its full clinical spectrum remains undefined. We present a biopsy proven case of IgG4-RD presenting with a parapharyngeal mass with intracranial extension and possible involvement of the brain parenchyma. We highlight the importance of considering the diagnosis in those presenting with tumefactive lesions, leptomeningitis or pachymeningitis and emphasise the value of securing a tissue diagnosis so that appropriate long-term treatment can be instigated and complications avoided. PMID- 26856358 TI - Characteristics of Sexual Abuse Among Individuals With Serious Mental Illnesses. AB - The deleterious effects of sexual abuse (SA) are well documented, as many studies have found that SA can increase the risk for psychiatric disorders. While SA has been examined in multiple samples, no studies have examined the characteristics of SA in individuals with severe mental illnesses (SMI). This study examined the prevalence rate and characterized the nature of SA among individuals with SMI who were under psychiatric care in three different inpatient facilities. Utilizing data from the MacArthur Violence Risk Assessment Study, 1,136 individuals with SMI were assessed for SA histories, psychiatric diagnoses, and other demographics. Nearly half of this sample ( n = 511) identified SA histories, with almost half indicating that the person was a stranger or someone outside of the family unit. One third reported SA occurred "too many times to count," and approximately a third indicated the abuse consisted of intercourse, occurring at a mean age of 11.22 years. Results found that individuals with SA histories were often never married, Caucasian, female, had children, described themselves as psychologically unwell, and were commonly voluntary psychiatric admissions. Those with SA histories had significantly higher psychopathology and lower functioning, and were more likely to be diagnosed with depression but less likely to be substance dependent. Identifying SA characteristics in individuals with SMI is a critical component to successful treatment. Thorough screening and assessment of this common problem can help clinicians identify accompanying issues that may exacerbate SMI symptomology, and improve the prognosis for long-term outcomes. PMID- 26856359 TI - Is the Use of Protective Behavioral Strategies Associated With College Sexual Assault Victimization? A Prospective Examination. AB - Sexual assault protective behavioral strategies (PBS) may be negatively associated with sexual assault victimization. However, no studies to date have prospectively examined whether the use of sexual assault PBS is negatively associated with subsequent sexual assault experiences. The current study examined the association between the use of sexual assault PBS and subsequent sexual assault victimization severity. College women who reported engaging in heavy episodic drinking ( n = 77) were assessed online for their use of sexual assault PBS and history of sexual assault victimization. In addition, a 3-month follow-up survey was given assessing sexual assault victimization severity in the past 3 months. The use of sexual assault PBS was negatively associated with sexual assault severity in the 3-month follow-up period. Future research should further examine these PBS to create more college-specific PBS and to determine whether they are useful as risk-reduction strategies. PMID- 26856360 TI - Does Who You Know Affect How You Act? The Impact of Relationships on Bystander Intervention in Interpersonal Violence Situations. AB - This study utilized an experimental design to determine how bystanders would intervene in campus sexual assault (SA) or intimate partner violence (IPV) situations. Specifically, it examines whether the type of intervention (direct, indirect, or delegation) is associated with relational distance, the nature of the crime, or the sex of the bystander. A random sample of college students completed a web-based survey at a private university in the Midwest. Survey participants were randomly assigned two vignettes-an SA scenario ( n = 371) and an IPV scenario ( n = 350)-with one of three conditions: knew the victim, knew the perpetrator, or knew neither. Chi-square tests, binary logistic regressions, and predicted probabilities were conducted to test three hypotheses. Results indicate that relational distance affects how a bystander will intervene. In the SA vignette, students who knew the victim or perpetrator chose direct intervention. In the IPV vignette, students who knew the victim or perpetrator chose direct or indirect interventions. Students who knew neither the victim nor the perpetrator tended to choose to delegate the intervention to someone else for both crime types. Although there were differences by sex, the larger differences were between whether they knew someone or not. Still, men had the highest probability of directly intervening in the SA scenario, whereas women had the highest probability of indirectly intervening in the IPV scenario. The results of this study suggest that campus violence prevention programs should consider context-specific issues in their trainings such as relational distance and type of crime. PMID- 26856361 TI - The composition of demand for newly launched vaccines: results from the pneumococcal and rotavirus vaccine introductions in Ethiopia and Malawi. AB - Understanding post-launch demand for new vaccines can help countries maximize the benefits of immunization programmes. In particular, low- and middle-income countries (LMICs) should ensure adequate resource planning with regards to stock consumption and service delivery for new vaccines, whereas global suppliers must produce enough vaccines to meet demand. If a country underestimates the number of children seeking vaccination, a stock-out of commodities will create missed opportunities for saving lives. We describe the post-launch demand for the first dose of pneumococcal conjugate vaccine (PCV1) in Ethiopia and Malawi and the first dose of rotavirus vaccine (Rota1) in Malawi, with focus on the new birth cohort and the 'backlog cohort', comprised of older children who are still eligible for vaccination at the time of launch. PCV1 and Rota1 uptake were compared with the demand for the first dose of pentavalent vaccine (Penta1), a routine immunization that targets the same age group and immunization schedule. In the first year, the total demand for PCV1 was 37% greater than that of Penta1 in Ethiopia and 59% greater in Malawi. In the first 6 months, the demand of Rota1 was only 5.9% greater than Penta1 demand in Malawi. Over the first three post introduction months, 70.7% of PCV1 demand in Ethiopia and 71.5% of demand in Malawi came from children in the backlog cohort, whereas only 28.0% of Rota1 demand in Malawi was from the backlog cohort. The composition of demand was impacted by time elapsed since vaccine introduction and age restrictions. Evidence suggests that countries' plans should account for the impact of backlog demand, especially in the first 3 months post-introduction. LMICs should request for higher stock volumes when compared with routine needs, plan social mobilization activities to reach the backlog cohort and allocate human resources and cold chain capacity to accommodate high demand following vaccine introduction. PMID- 26856362 TI - Inequality and inequity in healthcare utilization in urban Nepal: a cross sectional observational study. AB - Inequality in access to quality healthcare is a major health policy challenge in many low- and middle-income countries. This study aimed to identify the major sources of inequity in healthcare utilization using a population-based household survey from urban Nepal. A cross-sectional survey was conducted covering 9177 individuals residing in 1997 households in five municipalities of Kathmandu valley between 2011 and 2012. The concentration index was calculated and a decomposition method was used to measure inequality in healthcare utilization, along with a horizontal inequity index (HI) to estimate socioeconomic inequalities in healthcare utilization. Results showed a significant pro-rich distribution of general healthcare utilization in all service providers (Concentration Index: 0.062, P < 0.001; HI: 0.029, P < 0.05) and private service providers (Concentration Index: 0.070, P < 0.001; HI: 0.030, P < 0.05). The pro rich distribution of probability in general healthcare utilization was attributable to inequalities in the level of household economic status (percentage contribution: 67.8%) and in the self-reported prevalence of non communicable diseases such as hypertension (36.7%) and diabetes (14.4%). Despite the provision of free services by public healthcare providers, our analysis found no evidence of the poor making more use of public health services (Concentration Index: 0.041, P = 0.094). Interventions to reduce the household economic burden of major illnesses, coupled with improvement in the management of public health facilities, warrant further attention by policy-makers. PMID- 26856363 TI - User fees exemptions alone are not enough to increase indigent use of healthcare services. AB - The aim of this study was to assess whether user fees exemptions increased healthcare services use among indigents in the Ouargaye district in Burkina Faso. In this pre-post study, we surveyed 1224 indigents in 2010 about their healthcare services use over the preceding 6 months. Of these, 540 subsequently received a user fees exemption card. A follow-up survey was conducted 1 year later with a 55.3% retention rate. Analyses were performed in accordance with Andersen and Newman's model (Societal and individual determinants of medical care utilization in the United States. Milbank Q 1973;51:95-124) to explain healthcare services use by considering predisposing and facilitating factors and health needs indicators. Logistic regression analyses were performed.Among indigents exempted from user fees, 46.2% increased their healthcare services use in 2011, as opposed to 42.1% among the non-exempted. Being exempted was not associated with increased use of services (odds ratio, OR = 1.1, 95% confidence interval, CI [0.80-1.51]). Regardless of whether they were exempted or not, the indigents most likely to have increased their healthcare services use were older than 69 years of age (OR = 1.66, 95% CI [1.05-2.64]), male (OR = 1.44, 95% CI [0.99-2.08]), in low-income households (OR = 1.71, 95% CI [1.15-2.54]), and had received financial support from their families to obtain healthcare (OR = 1.59, 95% CI [1.1-2.28]). The indigents' increased healthcare services use was not attributable to user fees exemptions. Some contamination of the intervention is conceivable. Interventions combining user fees exemptions with actions targeting other obstacles to healthcare access would probably be more effective in increasing indigents' use of healthcare centres. PMID- 26856364 TI - Farewell, king coal! AB - Coal mining provided the power for the industrial development of the West, at great cost to the health of the workforce and, from industrial pollution, of the population. Medical appreciation of the diseases of miners was slow to develop and has been marked by controversy relating to the roles of coal and quartz and the causation of emphysema. Research by the MRC and the British coal industry resolved these issues as the industry itself declined. However, from the research has come an understanding of the influence of inhalation of different inhaled pollutants on human health that has been applied to predicting and preventing possible hazards of developing nanotechnologies. PMID- 26856366 TI - Positional isomerism makes a difference: phosphonic acid anchoring ligands with thienyl spacers in copper(i)-based dye-sensitized solar cells. AB - With the aim of improving the photoconversion efficiencies of heteroleptic [Cu(Lanchor)(Lancillary)](+) dyes in n-type dye-sensitized solar cells (DSCs), the previously favoured anchor ((6,6'-dimethyl-[2,2'-bipyridine]-4,4' diyl)bis(4,1-phenylene))bis(phosphonic acid) (1) has been replaced by analogues 2 and 3 containing 2-thienyl spacers between the 2,2'-bipyridine metal-binding domain and the phosphonic acid anchoring groups. The synthesis and characterization of 2 and 3 (2-thienyl spacer with phosphonic acid in the 5- and 4-positions, respectively) are reported. A stepwise, on-surface method was used to assemble [Cu(Lanchor)(Lancillary)](+) dyes onto FTO/TiO2 electrodes with Lanchor = 1, 2 or 3, and Lancillary = 6,6'-bis(trifluoromethyl)-2,2'-bipyridine (4), 6-trifluoromethyl-2,2'-bipyridine (5), 6,6'-dimethyl-2,2'-bipyridine (6), and 6-methyl-2,2'-bipyridine (7). Changing the solvent in the dye-bath from CH2Cl2 to acetone had only a small effect on the photoconversion efficiencies of [Cu(1)(4)](+), [Cu(1)(5)](+) and [Cu(1)(6)](+); the optimal dye in this series was [Cu(1)(5)](+). Comparable DSC performances were achieved by using either anchor 1 or 2, but there is improved electron injection if the phosphonic acid group is in the 4- rather than 5-position of the thienyl ring (i.e. anchor 3 is superior to 2). Similar open-circuit voltages (VOC) are achieved on going from 1 to 3 with a given Lancillary; although there is typically a gain in short-circuit current denisty (JSC) on going from 1 or 3 to 2, there is an ~50-60 mV drop in VOC on introducing 2 as the anchor. The best photoconversion efficiencies are obtained for the dye [Cu(3)(5)](+) (eta = 2.40% relative to an N719 reference of 5.76%). The conclusions reached from plots of current-density (J) against potential (V), and external quantum efficiency spectra are supported by electrochemical impedance spectroscopic measurements. PMID- 26856365 TI - Historic air pollution exposure and long-term mortality risks in England and Wales: prospective longitudinal cohort study. AB - INTRODUCTION: Long-term air pollution exposure contributes to mortality but there are few studies examining effects of very long-term (>25 years) exposures. METHODS: This study investigated modelled air pollution concentrations at residence for 1971, 1981, 1991 (black smoke (BS) and SO2) and 2001 (PM10) in relation to mortality up to 2009 in 367,658 members of the longitudinal survey, a 1% sample of the English Census. Outcomes were all-cause (excluding accidents), cardiovascular (CV) and respiratory mortality. RESULTS: BS and SO2 exposures remained associated with mortality decades after exposure-BS exposure in 1971 was significantly associated with all-cause (OR 1.02 (95% CI 1.01 to 1.04)) and respiratory (OR 1.05 (95% CI 1.01 to 1.09)) mortality in 2002-2009 (ORs expressed per 10 MUg/m(3)). Largest effect sizes were seen for more recent exposures and for respiratory disease. PM10 exposure in 2001 was associated with all outcomes in 2002-2009 with stronger associations for respiratory (OR 1.22 (95% CI 1.04 to 1.44)) than CV mortality (OR 1.12 (95% CI 1.01 to 1.25)). Adjusting PM10 for past BS and SO2 exposures in 1971, 1981 and 1991 reduced the all-cause OR to 1.16 (95% CI 1.07 to 1.26) while CV and respiratory associations lost significance, suggesting confounding by past air pollution exposure, but there was no evidence for effect modification. Limitations include limited information on confounding by smoking and exposure misclassification of historic exposures. CONCLUSIONS: This large national study suggests that air pollution exposure has long-term effects on mortality that persist decades after exposure, and that historic air pollution exposures influence current estimates of associations between air pollution and mortality. PMID- 26856367 TI - Reliability, validity and responsiveness of the Arabic version of the Disability of Arm, Shoulder and Hand (DASH-Arabic). AB - PURPOSE: To investigate the psychometric properties (reliability, validity and responsiveness) of the DASH-Arabic in a cohort of Arabic patients presenting with various upper extremity conditions. METHODS: Participants were 139 patients with various upper extremity conditions, who completed the DASH-Arabic at the baseline, 2-5 days later and 30-36 days later. Participants completed demographic data forms, the SF-36 and VAS at baseline, and a Global Rating of Change scale at first and second follow-ups. RESULTS: Cronbach's alpha of the DASH-Arabic was 0.94. Test-retest reliability was excellent with an ICC of 0.97. The SEM was 3.50 and the MDC95 was 9.28. Construct validity of the DASH-Arabic with the SF-36 subscales and VAS scores ranged from r -0.32 to -0.57, all statistically significant (p < 0.001). The effect size (ES) for the DASH-Arabic was 1.39 and its standard response mean was 1.51. The area under the curve was 0.82 (95% CI = 0.72-0.92, p < 0.001). The optimally efficient cutoff for an improvement was found to be a difference of 15 DASH points. CONCLUSIONS: The DASH-Arabic is a reliable, valid and responsive upper extremity outcome measure for patients whose primary language is Arabic; it can be used to document patient status and outcomes and support evidence-based practice. Implications for Rehabilitation The DASH-Arabic demonstrated sound psychometric properties of reliability, validity and responsiveness. It is an effective patient status and outcome tool that will support evidence-based practice. This tool is recommended for evaluating upper extremity work-related injuries and tracking therapeutic outcomes. PMID- 26856368 TI - Predictors of Mortality in Abdominal Organ Transplant Recipients with Pseudomonas aeruginosa Infections. AB - BACKGROUND: Pseudomonas aeruginosa infection remains a common life-threatening complication after abdominal organ transplantation. The objective of the present study was to determine epidemiology and predictors of mortality in abdominal organ transplant recipients with P. aeruginosa infections. MATERIAL AND METHODS: A retrospective, double-center study was performed over a 12-year study period. The epidemiology of P. aeruginosa infections was investigated and the univariate and multivariate analyses were performed to identify the independent risk factors for crude and infection-related 30-day mortality in abdominal organ transplant recipients with P. aeruginosa infections. RESULTS: In this study, 60 episodes of P. aeruginosa infection occurring in 54 abdominal organ transplant recipients were enrolled. Postoperative P. aeruginosa infection occurred in 54 (2.8%) of 1935 abdominal organ transplant recipients. Most episodes of P. aeruginosa infections were nosocomial (75.9%, n=41). Among those 54 patients, 30 (55.6%) developed pulmonary infection and 13 (24.1%) developed bacteremia. In 25 of the 54 (46.3%) patients, P. aeruginosa isolates were multidrug resistant. There were 6 (11.1%) cases of septic shock, 18 (33.3%) infection-related deaths, and 21 (38.9%) crude 30-day deaths. Septic shock (odds ratio (OR)=13.46, 95% confidence interval (CI)=1.43-126.38, P=0.023) was identified as an independent risk factor for infection-related 30-day mortality. The risk factors independently associated with crude 30-day mortality included P. aeruginosa or concomitant bacteremia (OR=6.79, 95% CI=1.82-25.39, P=0.004) and a serum creatinine level of >=1.5 mg/dL (OR=4.62, 95% CI=1.11-19.16, P=0.035). CONCLUSIONS: The morbidity and mortality rates of P. aeruginosa infections were appreciable in abdominal organ transplant recipients. P. aeruginosa or concomitant bacteremia and an elevated serum creatinine level were associated with higher crude mortality, and septic shock independently predicted higher infection-related mortality. PMID- 26856369 TI - Continuous quantification of HER2 expression by microfluidic precision immunofluorescence estimates HER2 gene amplification in breast cancer. AB - Chromogenic immunohistochemistry (IHC) is omnipresent in cancer diagnosis, but has also been criticized for its technical limit in quantifying the level of protein expression on tissue sections, thus potentially masking clinically relevant data. Shifting from qualitative to quantitative, immunofluorescence (IF) has recently gained attention, yet the question of how precisely IF can quantify antigen expression remains unanswered, regarding in particular its technical limitations and applicability to multiple markers. Here we introduce microfluidic precision IF, which accurately quantifies the target expression level in a continuous scale based on microfluidic IF staining of standard tissue sections and low-complexity automated image analysis. We show that the level of HER2 protein expression, as continuously quantified using microfluidic precision IF in 25 breast cancer cases, including several cases with equivocal IHC result, can predict the number of HER2 gene copies as assessed by fluorescence in situ hybridization (FISH). Finally, we demonstrate that the working principle of this technology is not restricted to HER2 but can be extended to other biomarkers. We anticipate that our method has the potential of providing automated, fast and high-quality quantitative in situ biomarker data using low-cost immunofluorescence assays, as increasingly required in the era of individually tailored cancer therapy. PMID- 26856370 TI - Topographical pathways guide chemical microswimmers. AB - Achieving control over the directionality of active colloids is essential for their use in practical applications such as cargo carriers in microfluidic devices. So far, guidance of spherical Janus colloids was mainly realized using specially engineered magnetic multilayer coatings combined with external magnetic fields. Here we demonstrate that step-like submicrometre topographical features can be used as reliable docking and guiding platforms for chemically active spherical Janus colloids. For various topographic features (stripes, squares or circular posts), docking of the colloid at the feature edge is robust and reliable. Furthermore, the colloids move along the edges for significantly long times, which systematically increase with fuel concentration. The observed phenomenology is qualitatively captured by a simple continuum model of self diffusiophoresis near confining boundaries, indicating that the chemical activity and associated hydrodynamic interactions with the nearby topography are the main physical ingredients behind the observed behaviour. PMID- 26856371 TI - Bystanders, parcelling, and an absence of trust in the grooming interactions of wild male chimpanzees. AB - The evolution of cooperation remains a central issue in socio-biology with the fundamental problem of how individuals minimize the risks of being short-changed ('cheated') should their behavioural investment in another not be returned. Economic decisions that individuals make during interactions may depend upon the presence of potential partners nearby, which offers co operators a temptation to defect from the current partner. The parcelling model posits that donors subdivide services into parcels to force cooperation, and that this is contingent on opportunities for defection; that is, the presence of bystanders. Here we test this model and the effect of bystander presence using grooming interactions of wild chimpanzees. We found that with more bystanders, initiators gave less grooming at the beginning of the bout and were more likely to abandon a grooming bout, while bouts were less likely to be reciprocated. We also found that the groomer's initial investment was not higher among frequent groomers or stronger reciprocators, suggesting that contrary to current assumptions, grooming decisions are not based on trust, or bonds, within dyads. Our work highlights the importance of considering immediate social context and the influence of bystanders for understanding the evolution of the behavioural strategies that produce cooperation. PMID- 26856372 TI - Using a Machine Learning Approach to Predict Outcomes after Radiosurgery for Cerebral Arteriovenous Malformations. AB - Predictions of patient outcomes after a given therapy are fundamental to medical practice. We employ a machine learning approach towards predicting the outcomes after stereotactic radiosurgery for cerebral arteriovenous malformations (AVMs). Using three prospective databases, a machine learning approach of feature engineering and model optimization was implemented to create the most accurate predictor of AVM outcomes. Existing prognostic systems were scored for purposes of comparison. The final predictor was secondarily validated on an independent site's dataset not utilized for initial construction. Out of 1,810 patients, 1,674 to 1,291 patients depending upon time threshold, with 23 features were included for analysis and divided into training and validation sets. The best predictor had an average area under the curve (AUC) of 0.71 compared to existing clinical systems of 0.63 across all time points. On the heldout dataset, the predictor had an accuracy of around 0.74 at across all time thresholds with a specificity and sensitivity of 62% and 85% respectively. This machine learning approach was able to provide the best possible predictions of AVM radiosurgery outcomes of any method to date, identify a novel radiobiological feature (3D surface dose), and demonstrate a paradigm for further development of prognostic tools in medical care. PMID- 26856373 TI - Internal (His)6-tagging delivers a fully functional hetero-oligomeric class II chaperonin in high yield. AB - Group II chaperonins are ATP-ases indispensable for the folding of many proteins that play a crucial role in Archaea and Eukarya. They display a conserved two ringed assembly enclosing an internal chamber where newly translated or misfolded polypeptides can fold to their native structure. They are mainly hexadecamers, with each eight-membered ring composed of one or two (in Archaea) or eight (in Eukarya) different subunits. A major recurring problem within group II chaperonin research, especially with the hetero-oligomeric forms, is to establish an efficient recombinant system for the expression of large amounts of wild-type as well as mutated variants. Herein we show how we can produce, in E. coli cells, unprecedented amounts of correctly assembled and active alphabeta-thermosome, the class II chaperonin from Thermoplasma acidophilum, by introducing a (His)6-tag within a loop in the alpha subunit of the complex. The specific location was identified via a rational approach and proved not to disturb the structure of the chaperonin, as demonstrated by size-exclusion chromatography, native gel electrophoresis and electron microscopy. Likewise, the tagged protein showed an ATP-ase activity and an ability to refold substrates identical to the wild type. This tagging strategy might be employed for the overexpression of other recombinant chaperonins. PMID- 26856374 TI - A fluorescent graphitic carbon nitride nanosheet biosensor for highly sensitive, label-free detection of alkaline phosphatase. AB - Graphitic C3N4 (g-C3N4) nanosheets provide an attractive option for bioprobes and bioimaging applications. Utilizing highly fluorescent and water-dispersible ultrathin g-C3N4 nanosheets, a highly sensitive, selective and label-free biosensor has been developed for ALP detection for the first time. The developed approach utilizes a natural substrate of ALP in biological systems and thus affords very high catalytic efficiency. This novel biosensor is demonstrated to enable quantitative analysis of ALP in a wide range from 0.1 to 1000 U L(-1) with a low detection limit of 0.08 U L(-1), which is among the most sensitive assays for ALP. It is expected that the developed method may provide a low-cost, convenient, rapid and highly sensitive platform for ALP-based clinical diagnostics and biomedical applications. PMID- 26856375 TI - Development and validation of an interview-administered FFQ for assessment of vitamin D and calcium intakes in Finnish women. AB - Increased vitamin D fortification of dairy products has increased the supply of vitamin D-containing products with different vitamin D contents on the market in Finland. The authors developed a ninety-eight-item FFQ with eight food groups and with a question on supplementation to assess dietary and supplemental vitamin D and Ca intakes in Finnish women (60oN). The FFQ was validated in subgroups with different habitual vitamin D supplement use (0-57.5 ug/d) against the biomarker serum 25-hydroxyvitamin D (S-25(OH)D) and against 3-d food records (FR) (n 29 67). Median total vitamin D intake among participants was 9.4 (range 1.6-30.5) ug/d. Spearman's correlations for vitamin D and Ca ranged from 0.28 (P 0.146, FFQ v. S-25(OH)D, persons not using supplements) to 0.75 (P<0.001, FFQ v. FR, supplement use included). The correlations between the FFQ and S-25(OH)D concentrations improved within increasing supplement intake. The Bland-Altman analysis showed wide limits of agreement between FFQ and FR: for vitamin D between -7.8 and 8.8 ug/d and for Ca between -938 and 934 mg/d, with mean differences being 0.5 ug/d and 2 mg/d, respectively. The triads method was used to calculate the validity coefficients of the FFQ for vitamin D, resulting in a mean of 1.00 (95 % CI 0.59, 1.00) and a range from 0.33 to 1.00. The perceived variation in the estimates could have been avoided with a longer FR period and larger number of participants. The results are comparable with earlier studies, and the FFQ provides a reasonable estimation of vitamin D and Ca intakes. PMID- 26856377 TI - Diagnosis of a pericardial effusion with a thoracic aortic aneurysm by point-of care ultrasound. AB - We present a rare case of a young patient with chest pain whose ascending thoracic aortic aneurysm (TAA) was detected by point-of-care ultrasound (POCUS) leading to a successful surgical repair. POCUS identified a moderate pericardial effusion and an associated severely dilated ascending aorta. In this context, it is important to rule out aortic rupture and aortic dissection. We also discuss the epidemiology, complications, and management of TAAs as well as the role of cardiac POCUS in the diagnosis of thoracic aneurysmal disease. PMID- 26856376 TI - Evolutionary functional elaboration of the Elovl2/5 gene family in chordates. AB - The biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFA) provides an intriguing example on how multi-enzymatic cascades evolve. Essential LC-PUFA, such as arachidonic, eicosapentaenoic, and docosahexaenoic acids (DHA), can be acquired from the diet but are also endogenously retailored from C18 precursors through consecutive elongations and desaturations catalyzed, respectively, by fatty acyl elongase and desaturase enzymes. The molecular wiring of this enzymatic pathway defines the ability of a species to biosynthesize LC-PUFA. Exactly when and how in animal evolution a functional LC-PUFA pathway emerged is still elusive. Here we examine key components of the LC-PUFA cascade, the Elovl2/Elovl5 elongases, from amphioxus, an invertebrate chordate, the sea lamprey, a representative of agnathans, and the elephant shark, a basal jawed vertebrate. We show that Elovl2 and Elovl5 emerged from genome duplications in vertebrate ancestry. The single Elovl2/5 from amphioxus efficiently elongates C18 and C20 and, to a marked lesser extent, C22 LC-PUFA. Lamprey is incapable of elongating C22 substrates. The elephant shark Elovl2 showed that the ability to efficiently elongate C22 PUFA and thus to synthesize DHA through the Sprecher pathway, emerged in the jawed vertebrate ancestor. Our findings illustrate how non-integrated "metabolic islands" evolve into fully wired pathways upon duplication and neofunctionalization. PMID- 26856378 TI - Surgical Team Stability and Risk of Sharps-Related Blood and Body Fluid Exposures During Surgical Procedures. AB - OBJECTIVE: To explore whether surgical teams with greater stability among their members (ie, members have worked together more in the past) experience lower rates of sharps-related percutaneous blood and body fluid exposures (BBFE) during surgical procedures. DESIGN: A 10-year retrospective cohort study. SETTING: A single large academic teaching hospital. PARTICIPANTS: Surgical teams participating in surgical procedures (n=333,073) performed during 2001-2010 and 2,113 reported percutaneous BBFE were analyzed. METHODS: A social network measure (referred to as the team stability index) was used to quantify the extent to which surgical team members worked together in the previous 6 months. Poisson regression was used to examine the effect of team stability on the risk of BBFE while controlling for procedure characteristics and accounting for procedure duration. Separate regression models were generated for percutaneous BBFE involving suture needles and those involving other surgical devices. RESULTS The team stability index was associated with the risk of percutaneous BBFE (adjusted rate ratio, 0.93 [95% CI, 0.88-0.97]). However, the association was stronger for percutaneous BBFE involving devices other than suture needles (adjusted rate ratio, 0.92 [95% CI, 0.85-0.99]) than for exposures involving suture needles (0.96 [0.88-1.04]). CONCLUSIONS: Greater team stability may reduce the risk of percutaneous BBFE during surgical procedures, particularly for exposures involving devices other than suture needles. Additional research should be conducted on the basis of primary data gathered specifically to measure qualities of relationships among surgical team personnel. PMID- 26856379 TI - Spin-orbit torque in Pt/CoNiCo/Pt symmetric devices. AB - Current induced magnetization switching by spin-orbit torques offers an energy efficient means of writing information in heavy metal/ferromagnet (FM) multilayer systems. The relative contributions of field-like torques and damping-like torques to the magnetization switching induced by the electrical current are still under debate. Here, we describe a device based on a symmetric Pt/FM/Pt structure, in which we demonstrate a strong damping-like torque from the spin Hall effect and unmeasurable field-like torque from Rashba effect. The spin-orbit effective fields due to the spin Hall effect were investigated quantitatively and were found to be consistent with the switching effective fields after accounting for the switching current reduction due to thermal fluctuations from the current pulse. A non-linear dependence of deterministic switching of average Mz on the in plane magnetic field was revealed, which could be explained and understood by micromagnetic simulation. PMID- 26856380 TI - Eastern region represents a worrying cluster of active hepatitis C in Algeria in 2012. AB - Algeria is the largest country of Africa, peopled with populations living a range of traditional/rural and modern/urban lifestyles. The variations of prevalence of chronic active hepatitis care poorly known on the Algerian territory. We conducted a retrospective survey on all patients (n = 998) referred to our institution in 2012 and confirmed by us for an active hepatitis C. Half of the hepatitis C virus (HCV) isolates were genotyped. Forty Algerian regions out of the 48 were represented in our study. Three geographical clusters (Ain Temouchent/SidiBelAbbes, Algiers, and a large Eastern region) with an excess of active hepatitis C were observed. Patients coming from the Eastern cluster (Batna, Khenchela, Oum el Bouaghi, and Tebessa) were strongly over-represented (49% of cases, OR = 14.5, P < 0.0001). The hallmarks of Eastern region were an excess of women (65% vs. 46% in the remaining population, P < 0.0001) and the almost exclusive presence of HCV genotype 1 (93% vs. 63%, P = 0.0001). The core of the epidemics was apparently located in Khenchela (odds ratio = 24.6, P < 0.0001). This situation is plausibly connected with nosocomial transmission or traditional practices as scarification (Hijama), piercing or tattooing, very lively in this region. Distinct hepatitis C epidemics are currently affecting Algerian population. The most worrying situation is observed in rural regions located east of Algeria. J. Med. Virol. 88:1394-1403, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26856382 TI - I can still write. PMID- 26856383 TI - Airway, sleep, and respiratory reflux. PMID- 26856381 TI - Real-Time MRI-Guided Cardiac Cryo-Ablation: A Feasibility Study. AB - INTRODUCTION: MRI-based ablation provides an attractive capability of seeing ablation-related tissue changes in real time. Here we describe a real-time MRI based cardiac cryo-ablation system. METHODS: Studies were performed in canine model (n = 4) using MR-compatible cryo-ablation devices built for animal use: focal cryo-catheter with 8 mm tip and 28 mm diameter cryo-balloon. The main steps of MRI-guided cardiac cryo-ablation procedure (real-time navigation, confirmation of tip-tissue contact, confirmation of vessel occlusion, real-time monitoring of a freeze zone formation, and intra-procedural assessment of lesions) were validated in a 3 Tesla clinical MRI scanner. RESULTS: The MRI compatible cryo devices were advanced to the right atrium (RA) and right ventricle (RV) and their position was confirmed by real-time MRI. Specifically, contact between catheter tip and myocardium and occlusion of superior vena cava (SVC) by the balloon was visually validated. Focal cryo-lesions were created in the RV septum. Circumferential ablation of SVC-RA junction with no gaps was achieved using the cryo-balloon. Real-time visualization of freeze zone formation was achieved in all studies when lesions were successfully created. The ablations and presence of collateral damage were confirmed by T1-weighted and late gadolinium enhancement MRI and gross pathological examination. CONCLUSION: This study confirms the feasibility of a MRI-based cryo-ablation system in performing cardiac ablation procedures. The system allows real-time catheter navigation, confirmation of catheter tip-tissue contact, validation of vessel occlusion by cryo-balloon, real time monitoring of a freeze zone formation, and intra-procedural assessment of ablations including collateral damage. PMID- 26856384 TI - Mandibular movement during speech of two related Latin languages. AB - OBJECTIVES/HYPOTHESIS: This study assessed the kinesiographic recordings of jaw movements during reading a text in Galician and Spanish language. STUDY DESIGN: Cross-sectional blind study. METHODS: A homogeneous healthy group of 25 normal stomatognathic system and native Galician participants was studied. Frontal and parasagittal plane recordings of the intraborder lateral jaw movements and during reading Galician and Spanish texts were recorded using a calibrated jaw-tracking device, kinesiograph. RESULTS: Although movements were similar in both languages, a greater retrusion of the jaw in the Spanish language was shown; moreover, a tendency exists for a left-side motion envelope in this right-handedness preference sample. CONCLUSIONS: This study supports the hypothesis that speech is controlled by the central nervous system rather than by peripheral factors and that the hemispheric dominance influences the asymmetry of the speech envelope. PMID- 26856386 TI - Life span and structure of ephemeral root modules of different functional groups from a desert system. AB - The terminal branch orders of plant root systems have been proposed as short lived 'ephemeral' modules specialized for resource absorption. The occurrence of ephemeral root modules has so far only been reported for a temperate tree species and it is unclear if the concept also applies to other woody (shrub, tree) and herb species. Fine roots of 12 perennial dicotyledonous herb, shrub and tree species were monitored for two growing seasons using a branch-order classification, sequential sampling and rhizotrons in the Taklamakan desert. Two root modules existed in all three plant functional groups. Among the first five branch orders, the first two (perennial herbs, shrubs) or three (trees) root orders were ephemeral and had a primary anatomical structure, high nitrogen (N) concentrations, high respiration rates and very short life spans of 1-4 months, whereas the last two branch orders in all functional groups were perennial, with thicker diameters, no or collapsed cortex, distinct secondary growth, low N concentrations, low respiration rates, but much longer life spans. Ephemeral, short-lived root modules and long-lived, persistent root modules seem to be a general feature across many plant functional groups and could represent a basic root system design. PMID- 26856387 TI - Dental pulp stem cells grown on dental implant titanium surfaces: An in vitro evaluation of differentiation and microRNAs expression. AB - The surface roughness of dental implants influences the proliferation and differentiation rate of adult mesenchymal stem cells (MSCs). The aim of the present study was to evaluate whether specifically treated titanium implant surfaces influenced human dental pulp stem cells (DPSCs) differentiation in an osteogenic pattern through modulation of microRNAs expression. The degree of differentiation was evaluated after 7, 14, and 21 days, through the expression of microRNAs characterizing the osteogenesis (miR-133 and miR-135), of Runx2 and Smad5 (key factor transcriptions associated with osteoblast differentiation) and Osteocalcin, marker for the bone formation process. DPSCs were cultured on sandblasted and acid-etched titanium disks, with (Test) or without the presence of ions (Control). Early differentiation of DPSCs cultured on titanium could be detected at all the evaluated time points, respect to cells grown alone. Moreover, the Test surfaces seemed to induce a more marked cells differentiation. The obtained results demonstrated that microRNAs played a pivotal role in the differentiation of MSCs and could be used as marker of osteogenic differentiation. Furthermore, the evaluated ionized sandblasted and acid-etched surface seemed to markedly enhance the development of osteoblast cells. A faster osseointegration could be achieved in the presence of specifically treated implant surfaces, promising encouraging clinical outcomes. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 953-965, 2017. PMID- 26856388 TI - A Systematic Review of Outcomes Following Immediate Molar Implant Placement Based on Recently Published Studies. AB - BACKGROUND: Immediate implant placement in molar extraction sites has become a treatment option for experienced clinicians. PURPOSE: The aim of this study was to provide a systematic review and meta-analysis of outcomes from recent clinical studies with immediate molar implants. MATERIALS AND METHODS: A systematic review was undertaken of relevant literature published from November 2008 to May 2015. Data collected included implant survival rates after at least 1 year in function, cumulative crestal bone loss, and implant location (maxilla vs mandible) and diameter. Implant diameters were grouped as "wide" (4-6 mm) or "ultra-wide" (>6-9 mm). Survival and bone loss with 95% CIs were calculated using a random effects model. Meta-analysis techniques were used to compare survival rates and cumulative mean bone loss between immediate and delayed placement implants. Survival rates also were computed and compared between wide and ultra-wide implants using chi-square testing. The quality of each study was assessed using established criteria. RESULTS: The literature search provided 15 papers published between November 2008 and May 2015 that satisfied the inclusion criteria. Data on survival were found for a total of 768 immediate molar implants inserted in 757 patients. Meta-analysis of these data showed an implant survival rate of 98% with no difference between maxilla and mandible. Five studies included delayed molar implants as controls, and no significant differences were detected. A significant difference (p = .048) was found in relation to implant diameter with implant failures being higher (3.67 vs 1.45%) for ultra-wide (>6-9 mm) versus wide (4-6 mm) implants. The majority of the 15 studies were determined to be either "average" (prospective case series) or "fair" (retrospective) in quality. CONCLUSION: While there are still no published reports from double-blind, randomized, controlled (best quality) clinical trials of immediate molar implant placement, high survival rates have been reported. The present data, however, suggests that there may be an optimal diameter for this implant application. Meta analysis of the limited bone loss data reported estimated the overall mean cumulative bone loss after at least 1 year to be 0.57 mm. PMID- 26856389 TI - Urinary metabolite profiling provides potential differentiation to explore the mechanisms of adjuvant-induced arthritis in rats. AB - To explore the pathogenesis of rheumatoid arthritis (RA) from the perspective of metabolomics, gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) technology was used to observe changes in the metabolic profiles of urine output from rats with adjuvant-induced arthritis (AA). Sprague-Dawley rats were randomly divided into a control group and an experimental group, with eight in each. Rats in the experimental group were induced by intracutaneous innoculation of 0.1 mL Freund's complete adjuvant to right paws. On day 20 after immunization, the metabolic profiles between rat control and experimental groups were compared by combining GC-TOF/MS technology with multivariate statistical approaches, including principal component analysis, partial least squares discriminant analysis and orthogonal projections to latent structures-discriminant analysis. Nine potential biomarkers were identified, including 2,2-dimethylsuccinic acid, tartronic acid, dehydroshikimic acid, hippuric acid, adenine, phenaceturic acid, l-dopa, 1,4-dihydroxy-2-naphthoic acid and melibiose. The findings indicate that the rats with AA are disturbed in metabolism of purine, amino acid, fat and energy. This study also demonstrates that the dysfunction in a range of biosynthetic and catabolic pathways, which leads to increased oxygen free radicals and inflammation, could cause underlying pathogenesis of RA. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26856390 TI - DESC1, a novel tumor suppressor, sensitizes cells to apoptosis by downregulating the EGFR/AKT pathway in esophageal squamous cell carcinoma. AB - Esophageal cancer is ranked as the eighth most common cancer and the sixth leading cause of cancer deaths worldwide. To identify candidate tumor suppressor genes related to esophageal squamous cell carcinoma (ESCC) development, a cDNA microarray analysis was performed using paired tumor and nontumor tissue samples from ESCC patients. Differentially expressed in squamous cell carcinoma 1 (DESC1), which belongs to the Type II transmembrane serine protease family, was frequently downregulated in ESCC. This study aims to elucidate the molecular mechanism for the tumor suppressive function of DESC1 in ESCC. We show that DESC1 reduced cell viability and sensitized cells to apoptosis, when cells were under apoptotic stimuli. The proapoptotic effect of DESC1 was mediated through downregulating AKT1 activation and the restoration of AKT activation by the introduction of the constitutively active AKT, myr-AKT, abolished the apoptosis sensitizing effect of DESC1. DESC1 also reduced EGFR protein level, which was abrogated when the proteolytic function of DESC1 was lost, suggesting that DESC1 cleaved EGFR and downregulated the EGFR/AKT pathway to favor apoptosis. The transmembrane localization and the structural domains provide an opportunity for DESC1 to interact with the extracellular environment. The importance of such interaction was highlighted by the finding that DESC1 reduced cell colony formation ability in three-dimensional culture. In line with this, DESC1 reduced tumor growth kinetics in the in vivo orthotopic tumorigenesis assay. Taken together, our novel findings suggest how DESC1 may suppress ESCC development by sensitizing cells to apoptosis under an apoptotic stimulus through downregulating the EGFR/AKT signaling pathway. PMID- 26856391 TI - An Approach to Cluster EU Member States into Groups According to Pathways of Salmonella in the Farm-to-Consumption Chain for Pork Products. AB - The aim of the project as the cluster analysis was to in part to develop a generic structured quantitative microbiological risk assessment (QMRA) model of human salmonellosis due to pork consumption in EU member states (MSs), and the objective of the cluster analysis was to group the EU MSs according to the relative contribution of different pathways of Salmonella in the farm-to consumption chain of pork products. In the development of the model, by selecting a case study MS from each cluster the model was developed to represent different aspects of pig production, pork production, and consumption of pork products across EU states. The objective of the cluster analysis was to aggregate MSs into groups of countries with similar importance of different pathways of Salmonella in the farm-to-consumption chain using available, and where possible, universal register data related to the pork production and consumption in each country. Based on MS-specific information about distribution of (i) small and large farms, (ii) small and large slaughterhouses, (iii) amount of pork meat consumed, and (iv) amount of sausages consumed we used nonhierarchical and hierarchical cluster analysis to group the MSs. The cluster solutions were validated internally using statistic measures and externally by comparing the clustered MSs with an estimated human incidence of salmonellosis due to pork products in the MSs. Finally, each cluster was characterized qualitatively using the centroids of the clusters. PMID- 26856392 TI - World Kidney Day 2016 Averting The Legacy of Kidney Disease-Focus On Childhood. AB - World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID- 26856395 TI - Robot-assisted total knee arthroplasty in haemophilic arthropathy. AB - INTRODUCTION: Execution of total knee arthroplasty (TKA) in end-stage haemophilic arthropathy is challenging because of soft tissue fibrosis, flexion contractures, poor quality of the bone, and the altered bony anatomy. Restoring the lower limb alignment and achieving range of motion (ROM) is difficult. Robots have been used in TKA to reduce the chances of malalignment and improve accuracy and precision. However, there has been no report in literature on use of robots for TKA in haemophilic arthropathy. The aim of this study was to evaluate whether robot assisted TKA can be successfully carried out in haemophilic arthropathy and what precision could be obtained. METHODS: Thirty-two robot-assisted TKA were evaluated in 29 haemophilia patients. The mean follow up period was 5 years (range, 3-7 years). Hip-knee-ankle (HKA) axis, component angles, and radiographic loosening were evaluated. Clinically ROM, Knee Society scores (KSS) and SF-36 were assessed. RESULTS: The HKA axis was within a range of 0 +/- 3 degrees in 30 knees (93.8%). The alignment of the components also presented satisfying results. KSS were improved from 27.1 to 82.8 postoperatively (P < 0.001). The ROM was improved from 70.7 to 84.7 postoperatively (P = 0.006). Complications included early haematoma in three knees, heterotopic ossification in three knees, periprosthetic infection in two knees. CONCLUSIONS: Though robotic TKA gives excellent accuracy of lower limb and component alignment, expensive cost, additional preparation time, longer operation time with similar clinical results in haemophilic arthropathy should be concerned. PMID- 26856396 TI - Differential Neural Correlates of Set-Shifting in the Bingeing-Purging and Restrictive Subtypes of Anorexia Nervosa: An fMRI Study. AB - In this study, possible differences in the neural correlates of set-shifting abilities between the restrictive (AN-R) and bingeing/purging (AN-BP) subtypes of anorexia nervosa have been explored. Three groups of participants performed a set shifting task during functional magnetic resonance imaging: patients with AN-R (N = 16), AN-BP (N = 13) and healthy control participants (N = 15). As in a typical set-shifting experiment, participants had to switch between two easy tasks (i.e. 'Is the presented number odd/even' or 'Is the presented number smaller/larger than 5'). The trials in which the task was repeated (repeat trials) were compared with trials in which the task was switched (switch trials). With regards to the level of task performance, no significant group differences could be established. However, when comparing switch specific brain activity across study groups, a stronger activation was found in the insula and the precuneus in AN-R when compared to AN-BP and HC. These results suggest that the both subtypes of AN might have different neurobiological correlates, and thus, might benefit from different treatment approaches. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association. PMID- 26856397 TI - Individual differences in in vitro and in vivo metabolic clearances of the antipsychotic drug olanzapine from non-smoking and smoking Japanese subjects genotyped for cytochrome P4502D6 and flavincontaining monooxygenase 3. AB - OBJECTIVE: The antipsychotic olanzapine is reportedly metabolized by inducible human cytochrome P450 (CYP) 1A2 and variable copy-number CYP2D6 and polymorphic flavin-containing monooxygenase 3 (FMO3) in different pathways. We investigated individual differences in the metabolite formation and clearance of olanzapine in vitro and in vivo. METHODS: Human liver microsomal olanzapine oxidation activities were evaluated, and plasma concentrations of olanzapine were determined in 21 Japanese patients (mean age: 50 years, range: 32-69 years, 14 male and 7 female, including 6 smokers) genotyped for CYP2D6 (*1, *5, and *10) and FMO3 (E158K, C197fsX, R205C, V257M, E308G, and R500X). RESULTS: Furafylline (a CYP1A2 inhibitor), quinidine (a CYP2D6 inhibitor), and heat treatment (inactivates FMO3) suppressed liver microsomal metabolic clearance of olanzapine by approximately 30%. Olanzapine N-demethylation and N-oxygenation were found to be catalyzed by CYP1A2 and CYP2D6 and by CYP2D6 and FMO3, respectively, in experiments using liver microsomes and recombinant enzymes. Plasma concentrations and clearance of olanzapine were not affected by CYP2D6 or FMO3 genotypes or smoking behavior. CONCLUSIONS: Olanzapine clearance was not affected by CYP2D6 or FMO3 genotypes or smoking behavior as a single factor under the present conditions because olanzapine clearance is mediated by multiple enzymes involved in two major and one minor pathways. PMID- 26856399 TI - Guided bone regeneration and abutment connection augment the buccal soft tissue contour: 3-year results of a prospective comparative clinical study. AB - AIM: To test whether implant placement with simultaneous guided bone regeneration (GBR) differs from implant placement without GBR regarding the change in marginal mucosal contour. MATERIALS AND METHODS: In 28 patients, single implants were placed >4 months after tooth extraction. Eighteen implants were completely surrounded by native bone, and no bone augmentation was performed. At 10 implant sites, bone defects and thin bone plates were grafted with deproteinized bovine derived bone mineral and covered with collagen membrane. Impressions were taken prior to implant placement (baseline), at 3 months before abutment connection, at 6 months immediately after crown insertion, at 1 year, and at 3 years. Models were optically scanned and 3D images were superimposed for the evaluation of mucosal contour changes at the mid-buccal aspect. The nonparametric Mann-Whitney U-test was applied to detect differences. RESULTS: From baseline to 6 months, horizontal contour change at the level 1 and 2 mm apical to the mucosal margin measured 0.65 +/- 0.74 mm and 0.55 +/- 0.56 mm at sites without GBR, and 1.92 +/- 0.87 mm and 1.76 +/- 0.70 mm at sites with GBR (P < 0.05). In the period from baseline to 1 year, the corresponding values amounted to 0.81 +/- 0.67 mm and 0.60 +/- 0.55 mm in the group without GBR, and to 1.81 +/- 0.86 mm and 1.37 +/- 0.62 mm in the group with GBR (P < 0.05). From baseline to 6 months, mucosal margin moved 0.16 +/- 0.49 mm in the coronal direction in the group without GBR and 0.82 +/- 0.65 mm in the group with GBR (P < 0.05). In the period from baseline to 1 year, vertical change of mucosal margin amounted to 0.64 +/- 0.54 mm in the group without GBR and to 1.17 +/- 0.53 mm in the GBR group (P < 0.05). From 1 to 3 years, the mucosal contours remained stable. CONCLUSIONS: Implant placement with simultaneous GBR resulted in more gain of buccal soft tissue contour in comparison with implant placement without GBR. Abutment connection increased the contour of the marginal mucosa at the augmented and the nonaugmented sites. GBR procedure contributed more to the contour gain than did the abutment connection. The augmented and the nonaugmented ridges exhibited stable peri-implant mucosal contour over a 3-year period. PMID- 26856398 TI - Hereditary spastic paraplegia: Clinicogenetic lessons from 608 patients. AB - OBJECTIVE: Hereditary spastic paraplegias (HSPs) are genetically driven disorders with the hallmark of progressive spastic gait disturbance. To investigate the phenotypic spectrum, prognostic factors, and genotype-specific differences, we analyzed baseline data from a continuous, prospective cohort. METHODS: We recruited 608 HSP cases from 519 families of mostly German origin. Clinical severity was assessed by the Spastic Paraplegia Rating Scale. Complicating symptoms were recorded by a standardized inventory. RESULTS: Family history indicated dominant (43%), recessive (10%), and simplex (47%) disease. We observed a significant male predominance, particularly in simplex cases without a genetic diagnosis. Disease severity increased with disease duration. Earlier disease onset was associated with less severe disease. Specific complicating features including cognitive impairment, extrapyramidal or peripheral motor involvement, and ataxia were associated with worse disease severity. Disease severity also depended on the genotype. HSP cases maintained the ability to walk independently for a median disease duration of 22 years. Early onset cases were able to maintain free walking significantly longer and were at less risk to become wheelchair dependent. INTERPRETATION: This cross-sectional cohort study provides the first large-scale data on disease manifestation, progression, and modifying factors, with relevance for counseling of HSP families and planning of future cross-sectional and natural history studies. Later age of onset, specific complicating features, and the SPG11 genotype are strongly associated with more severe disease. Future interventional studies will require stratification for modifiers of disease progression identified in this study. Prospective longitudinal studies will verify progression rates calculated in this baseline analysis. PMID- 26856400 TI - Using autologous platelet-rich plasma for the treatment of complex fistulas. AB - OBJECTIVE: This study aims to demonstrate the effectiveness and safety of autologous fibrin gel rich in platelet growth factors for the treatment of complex perianal fistulas. MATERIAL AND METHODS: Prospective epidemiological study. Patients with complex perianal fistula or perianal fistula mere alteration of continence are included. identification of both holes and the journey, curettage of it and instillation of Vivostat PRF(r) in the way it is done to observe excess material by OFE. The variables analyzed were: age, sex, use of prior Seton clinic prevalent type of fistula, postoperative complications, fistula closure and impaired quality of life using the SF-36 test (v2). RESULTS: From January 2011 to May 2013 have involved 23 patients, 12 men and 11 women, with an average age of 49 years and a minimum follow-up of 12 months. Two dropped out. 17 patients had low transsphincteric fistulas, 2 and 2 high transsphincteric intersphincteric with impaired continence. The most common symptom is the discharge. Twelve patients had a loose seton (62%), of which nine cured. Of all the patients we have operated the success rate is 62%. No patient developed incontinence after treatment. Only two reported a worse quality of life after surgery. CONCLUSION: This study demonstrates that there is a clear benefit to the use of Vivostat PRF(r) as a treatment for complex perianal fistulas. It is a highly reproducible technique with acceptable results and does not produce impairment of continence. PMID- 26856401 TI - Twin anchors of the soybean isoflavonoid metabolon: evidence for tethering of the complex to the endoplasmic reticulum by IFS and C4H. AB - Isoflavonoids are specialized plant metabolites, almost exclusive to legumes, and their biosynthesis forms a branch of the diverse phenylpropanoid pathway. Plant metabolism may be coordinated at many levels, including formation of protein complexes, or 'metabolons', which represent the molecular level of organization. Here, we have confirmed the existence of the long-postulated isoflavonoid metabolon by identifying elements of the complex, their subcellular localizations and their interactions. Isoflavone synthase (IFS) and cinnamate 4-hydroxylase (C4H) have been shown to be tandem P450 enzymes that are anchored in the ER, interacting with soluble enzymes of the phenylpropanoid and isoflavonoid pathways (chalcone synthase, chalcone reductase and chalcone isomerase). The soluble enzymes of these pathways, whether localized to the cytoplasm or nucleus, are tethered to the ER through interaction with these P450s. The complex is also held together by interactions between the soluble elements. We provide evidence for IFS interaction with upstream and non-consecutive enzymes. The existence of such a protein complex suggests a possible mechanism for flux of metabolites into the isoflavonoid pathway. Further, through interaction studies, we identified several candidates that are associated with GmIFS2, an isoform of IFS, in soybean hairy roots. This list provides additional candidates for various biosynthetic and structural elements that are involved in isoflavonoid production. Our interaction studies provide valuable information about isoform specificity among isoflavonoid enzymes, which may guide future engineering of the pathway in legumes or help overcome bottlenecks in heterologous expression. PMID- 26856402 TI - Proposal of indicators to evaluate complementary feeding based on World Health Organization indicators. AB - This study compares complementary feeding World Health Organization (WHO) indicators with those built in accordance with Brazilian recommendations (Ten Steps to Healthy Feeding). A cross-sectional study was carried out during the National Immunization Campaign against Poliomyelitis in Guarapuava-Parana, Brazil, in 2012. Feeding data from 1,355 children aged 6-23 months were obtained through the 24 h diet recall. Based on five indicators, the proportion of adequacy was evaluated: introduction of solid, semi-solid, or soft foods; minimum dietary diversity; meal frequency; acceptable diet; and consumption of iron-rich foods. Complementary feeding showed adequacy higher than 85% in most WHO indicators, while review by the Ten Steps assessment method showed a less favorable circumstance and a high intake of unhealthy foods. WHO indicators may not reflect the complementary feeding conditions of children in countries with low malnutrition rates and an increased prevalence of overweight/obesity. The use of indicators according to the Ten Steps can be useful to identify problems and redirect actions aimed at promoting complementary feeding. PMID- 26856403 TI - Culturalizing motivation research in educational psychology. PMID- 26856404 TI - Cultural invariance of goal orientation and self-efficacy in New Zealand: Relations with achievement. AB - BACKGROUND: There is substantial evidence indicating that various psychological processes are affected by cultural context, but such research is comparatively nascent within New Zealand. As there are four large cultural groups in New Zealand, representing an intersection of individualist, collectivist, indigenous, colonial, and immigrant cultures, New Zealand is an important context in which to investigate the role of culture in such processes. AIMS: This study investigated goal orientation and self-efficacy beliefs among students of different cultural backgrounds in New Zealand, associations between motivational beliefs and achievement, and whether any relations differed by cultural background. SAMPLE: Participants were 2,210 students attending three intermediate schools. METHODS: Participants responded to a questionnaire at the beginning of the school year to evaluate self-efficacy for mathematics and mastery and performance goal orientation. Participants also completed a standardized mathematics achievement test at the beginning and end of the year. RESULTS: The factor structure was sufficiently invariant by cultural group, but with statistically significant differences in average level of endorsement. Self-efficacy for mathematics predicted marginally higher end-of-year achievement after controlling for beginning-of-year achievement, with a stronger relationship for Maori and Pasifika, but no statistically significant relationship with achievement among Asian students. CONCLUSIONS: The questionnaire used was a valid instrument for the four main cultural groups in New Zealand. Differences were found in motivation levels, and Maori and Pasifika were more affected by their self reported self-efficacy. Teachers may be able to raise students' self-beliefs by conveying high expectations for these students, potentially supporting higher academic outcomes. PMID- 26856406 TI - HLA-DQA1/B1 alleles as putative susceptibility markers in congenital toxoplasmosis. AB - Host and parasite genotypes are among the factors associated with congenital toxoplasmosis pathogenesis. As HLA class II molecules play a key role in the immune system regulation, the aim of this study was to investigate whether HLA DQA1/B1 alleles are associated with susceptibility or protection to congenital toxoplasmosis. One hundred and twenty-two fetuses with and 103 without toxoplasmosis were studied. The two study groups were comparable according to a number of socio-demographic and genetic variables. HLA alleles were typed by PCR SSP. In the HLA-DQA1 region, the allele frequencies showed that *01:03 and *03:02 alleles could confer susceptibility (OR= 3.06, p = 0.0002 and OR= 9.60, p= 0.0001, respectively) as they were more frequent among infected fetuses. Regarding the HLA-DQB1 region, the *05:04 allele could confer susceptibility (OR = 6.95, p < 0.0001). Of the 122 infected fetuses, 10 presented susceptibility haplotypes contrasting with only one in the non-infected group. This difference was not statistically significant after correction for multiple comparison (OR = 9.37, p=0.011). In the casuistic, there were two severely damaged fetuses with high parasite loads determined in amniotic fluid samples and HLA-DQA1 susceptibility alleles. In the present study, a discriminatory potential of HLA DQA1/B1 alleles to identify susceptibility to congenital toxoplasmosis and the most severe cases has been shown. PMID- 26856408 TI - Corrigendum. PMID- 26856407 TI - Kinetic properties and substrate inhibition of alpha-galactosidase from Aspergillus niger. AB - The recombinant AglB produced by Pichia pastoris exhibited substrate inhibition behavior for the hydrolysis of p-nitrophenyl alpha-galactoside, whereas it hydrolyzed the natural substrates, including galactomanno-oligosaccharides and raffinose family oligosaccharides, according to the Michaelian kinetics. These contrasting kinetic behaviors can be attributed to the difference in the dissociation constant of second substrate from the enzyme and/or to the ability of the leaving group of the substrates. The enzyme displays the grater kcat/Km values for hydrolysis of the branched alpha-galactoside in galactomanno oligosaccharides than that of raffinose and stachyose. A sequence comparison suggested that AglB had a shallow active-site pocket, and it can allow to hydrolyze the branched alpha-galactosides, but not linear raffinose family oligosaccharides. PMID- 26856409 TI - Intrauterine growth restriction - part 1. AB - Intrauterine growth restriction (IUGR) is a major and silent cause of various morbidity and mortality for the fetal and neonatal population. It is defined as a rate of fetal growth that is less than normal for the growth potential of that specific infant. The terms IUGR and small for gestational age (SGA) are often used interchangeably, although there exists subtle differences between the two. IUGR/SGA is an end result of various etiologies that includes maternal, placental and fetal factors and recently added genetic factors too, also contribute to IUGR. In this review article we will cover the antenatal aspect of IUGR and management with proven preventive intervention. PMID- 26856410 TI - Aging augments the impact of influenza respiratory tract infection on mobility impairments, muscle-localized inflammation, and muscle atrophy. AB - Although the influenza virus only infects the respiratory system, myalgias are commonly experienced during infection. In addition to a greater risk of hospitalization and death, older adults are more likely to develop disability following influenza infection; however, this relationship is understudied. We hypothesized that upon challenge with influenza, aging would be associated with functional impairments, as well as upregulation of skeletal muscle inflammatory and atrophy genes. Infected young and aged mice demonstrated decreased mobility and altered gait kinetics. These declines were more prominent in hind limbs and in aged mice. Skeletal muscle expression of genes involved in inflammation, as well as muscle atrophy and proteolysis, increased during influenza infection with an elevated and prolonged peak in aged mice. Infection also decreased expression of positive regulators of muscle mass and myogenesis components to a greater degree in aged mice. Gene expression correlated to influenza-induced body mass loss, although evidence did not support direct muscle infection. Overall, influenza leads to mobility impairments with induction of inflammatory and muscle degradation genes and downregulation of positive regulators of muscle. These effects are augmented and prolonged with aging, providing a molecular link between influenza infection, decreased resilience and increased risk of disability in the elderly. PMID- 26856412 TI - Exciton diamagnetic shifts and valley Zeeman effects in monolayer WS2 and MoS2 to 65 Tesla. AB - In bulk and quantum-confined semiconductors, magneto-optical studies have historically played an essential role in determining the fundamental parameters of excitons (size, binding energy, spin, dimensionality and so on). Here we report low-temperature polarized reflection spectroscopy of atomically thin WS2 and MoS2 in high magnetic fields to 65 T. Both the A and B excitons exhibit similar Zeeman splittings of approximately -230 MUeV T(-1) (g-factor ?-4), thereby quantifying the valley Zeeman effect in monolayer transition-metal disulphides. Crucially, these large fields also allow observation of the small quadratic diamagnetic shifts of both A and B excitons in monolayer WS2, from which radii of ~1.53 and ~1.16 nm are calculated. Further, when analysed within a model of non-local dielectric screening, these diamagnetic shifts also constrain estimates of the A and B exciton binding energies (410 and 470 meV, respectively, using a reduced A exciton mass of 0.16 times the free electron mass). These results highlight the utility of high magnetic fields for understanding new two dimensional materials. PMID- 26856411 TI - Dictyocaulus viviparus genome, variome and transcriptome elucidate lungworm biology and support future intervention. AB - The bovine lungworm, Dictyocaulus viviparus (order Strongylida), is an important parasite of livestock that causes substantial economic and production losses worldwide. Here we report the draft genome, variome, and developmental transcriptome of D. viviparus. The genome (161 Mb) is smaller than those of related bursate nematodes and encodes fewer proteins (14,171 total). In the first genome-wide assessment of genomic variation in any parasitic nematode, we found a high degree of sequence variability in proteins predicted to be involved host parasite interactions. Next, we used extensive RNA sequence data to track gene transcription across the life cycle of D. viviparus, and identified genes that might be important in nematode development and parasitism. Finally, we predicted genes that could be vital in host-parasite interactions, genes that could serve as drug targets, and putative RNAi effectors with a view to developing functional genomic tools. This extensive, well-curated dataset should provide a basis for developing new anthelmintics, vaccines, and improved diagnostic tests and serve as a platform for future investigations of drug resistance and epidemiology of the bovine lungworm and related nematodes. PMID- 26856413 TI - Comparative genomic and functional analysis reveal conservation of plant growth promoting traits in Paenibacillus polymyxa and its closely related species. AB - Paenibacillus polymyxa has widely been studied as a model of plant-growth promoting rhizobacteria (PGPR). Here, the genome sequences of 9 P. polymyxa strains, together with 26 other sequenced Paenibacillus spp., were comparatively studied. Phylogenetic analysis of the concatenated 244 single-copy core genes suggests that the 9 P. polymyxa strains and 5 other Paenibacillus spp., isolated from diverse geographic regions and ecological niches, formed a closely related clade (here it is called Poly-clade). Analysis of single nucleotide polymorphisms (SNPs) reveals local diversification of the 14 Poly-clade genomes. SNPs were not evenly distributed throughout the 14 genomes and the regions with high SNP density contain the genes related to secondary metabolism, including genes coding for polyketide. Recombination played an important role in the genetic diversity of this clade, although the rate of recombination was clearly lower than mutation. Some genes relevant to plant-growth promoting traits, i.e. phosphate solubilization and IAA production, are well conserved, while some genes relevant to nitrogen fixation and antibiotics synthesis are evolved with diversity in this Poly-clade. This study reveals that both P. polymyxa and its closely related species have plant growth promoting traits and they have great potential uses in agriculture and horticulture as PGPR. PMID- 26856414 TI - Antiviral Activity of Hatay Propolis Against Replication of Herpes Simplex Virus Type 1 and Type 2. AB - BACKGROUND Propolis is a bee product widely used in folk medicine and possessing many pharmacological properties. In this study we aimed to investigate: i) the antiviral activities of Hatay propolis samples against HSV-1 and HSV-2 in HEp-2 cell line, and ii) the presence of the synergistic effects of propolis with acyclovir against these viruses. MATERIAL AND METHODS All experiments were carried out in HEp-2 cell cultures. Proliferation assays were performed in 24 well flat bottom microplates. We inoculated 1x105 cells per ml and RPMI 1640 medium with 10% fetal calf serum into each well. Studies to determine cytotoxic effect were performed. To investigate the presence of antiviral activity of propolis samples, different concentrations of propolis (3200, 1600, 800, 400, 200, 100, 75, 50, and 25 MUg/mL) were added into the culture medium. The amplifications of HSV-1 and HSV-2 DNA were performed by real-time PCR method. Acyclovir (Sigma, USA) was chosen as a positive control. Cell morphology was evaluated by scanning electron microscopy (SEM). RESULTS The replication of HSV-1 and HSV-2 was significantly suppressed in the presence of 25, 50, and 100 MUg/mL of Hatay propolis. We found that propolis began to inhibit HSV-1 replication after 24 h of incubation and propolis activity against HSV-2 was found to start at 48 h following incubation. The activity of propolis against both HSV-1 and HSV 2 was confirmed by a significant decrease in the number of viral copies. CONCLUSIONS We determined that Hatay propolis samples have important antiviral effects compared with acyclovir. In particular, the synergy produced by antiviral activity of propolis and acyclovir combined had a stronger effect against HSV-1 and HSV-2 than acyclovir alone. PMID- 26856415 TI - Bulging and Pulsating Conjunctiva. PMID- 26856417 TI - Summaries for Patients. Medicine and Nonmedicine Options for the Treatment of Adults With Major Depressive Disorder. PMID- 26856416 TI - Fate mapping reveals that microglia and recruited monocyte-derived macrophages are definitively distinguishable by phenotype in the retina. AB - The recent paradigm shift that microglia are yolk sac-derived, not hematopoietic derived, is reshaping our knowledge about the isolated role of microglia in CNS diseases, including degenerative conditions of the retina. However, unraveling microglial-specific functions has been hindered by phenotypic overlap of microglia with monocyte-derived macrophages. The latter are differentiated from recruited monocytes in neuroinflammation, including retina. Here we demonstrate the use of fate mapping wherein microglia and monocyte-derived cells are endogenously labeled with different fluorescent reporters. Combining this method with 12-color flow cytometry, we show that these two populations are definitively distinguishable by phenotype in retina. We prove that retinal microglia have a unique CD45(lo) CD11c(lo) F4/80(lo) I-A/I-E(-) signature, conserved in the steady state and during retinal injury. The latter was observed in the widely used light induced retinal degeneration model and corroborated in other models, including whole-body irradiation/bone-marrow transplantation. The literature contains conflicting observations about whether microglia, including in the retina, increase expression of these markers in neuroinflammation. We show that monocyte derived macrophages have elevated expression of these surface markers, not microglia. Our resolution of such phenotypic differences may serve as a robust way to help characterize isolated roles of these cells in retinal neuroinflammation and possibly elsewhere in CNS. PMID- 26856419 TI - Rhombic Coulomb diamonds in a single-electron transistor based on an Au nanoparticle chemically anchored at both ends. AB - Rhombic Coulomb diamonds are clearly observed in a chemically anchored Au nanoparticle single-electron transistor. The stability diagrams show stable Coulomb blockade phenomena and agree with the theoretical curve calculated using the orthodox model. The resistances and capacitances of the double-barrier tunneling junctions between the source electrode and the Au core (R1 and C1, respectively), and those between the Au core and the drain electrode (R2 and C2, respectively), are evaluated as 4.5 MOmega, 1.4 aF, 4.8 MOmega, and 1.3 aF, respectively. This is determined by fitting the theoretical curve against the experimental Coulomb staircases. Two-methylene-group short octanedithiols (C8S2) in a C8S2/hexanethiol (C6S) mixed self-assembled monolayer is concluded to chemically anchor the core of the Au nanoparticle at both ends between the electroless-Au-plated nanogap electrodes even when the Au nanoparticle is protected by decanethiol (C10S). This is because the R1 value is identical to that of R2 and corresponds to the tunneling resistances of the octanedithiol chemically bonded with the Au core and the Au electrodes. The dependence of the Coulomb diamond shapes on the tunneling resistance ratio (R1/R2) is also discussed, especially in the case of the rhombic Coulomb diamonds. Rhombic Coulomb diamonds result from chemical anchoring of the core of the Au nanoparticle at both ends between the electroless-Au-plated nanogap electrodes. PMID- 26856418 TI - Redifferentiation of expanded human islet beta cells by inhibition of ARX. AB - Ex-vivo expansion of adult human islet beta cells has been evaluated for generation of abundant insulin-producing cells for transplantation; however, lineage-tracing has demonstrated that this process results in beta-cell dedifferentiation. Redifferentiation of beta-cell-derived (BCD) cells can be achieved using a combination of soluble factors termed Redifferentiation Cocktail (RC); however, this treatment leads to redifferentiation of only a fraction of BCD cells. This study aimed at improving redifferentiation efficiency by affecting the balance of islet progenitor-cell transcription factors activated by RC treatment. Specifically, RC treatment induces the transcription factors PAX4 and ARX, which play key roles in directing pancreas endocrine progenitor cells into the beta/delta or alpha/PP developmental pathways, respectively. Misactivation of ARX in RC-treated BCD cells may inhibit their redifferentiation into beta cells. Blocking ARX expression by shRNA elevated insulin mRNA levels 12.8-fold, and more than doubled the number of insulin-positive BCD cells. ARX inhibition in expanded alpha-cell-derived cells treated with RC did not cause their transdifferentiation into insulin-producing cells. The combination of RC and ARX shRNA treatment may facilitate the generation of abundant insulin producing cells for transplantation into patients with type 1 diabetes. PMID- 26856420 TI - Estimation of fat-free mass in Asian neonates using bioelectrical impedance analysis. AB - The aims of this study were to develop and validate a prediction equation of fat free mass (FFM) based on bioelectrical impedance analysis (BIA) and anthropometry using air-displacement plethysmography (ADP) as a reference in Asian neonates and to test the applicability of the prediction equations in an independent Western cohort. A total of 173 neonates at birth and 140 at two weeks of age were included. Multiple linear regression analysis was performed to develop the prediction equations in a two-third randomly selected subset and validated on the remaining one-third subset at each time point and in an independent Queensland cohort. FFM measured by ADP was the dependent variable, and anthropometric measures, sex and impedance quotient (L2/R50) were independent variables in the model. Accuracy of prediction equations was assessed using intra-class correlation and Bland-Altman analyses. L2/R50 was the significant predictor of FFM at week two but not at birth. Compared with the model using weight, sex and length, including L2/R50 slightly improved the prediction with a bias of 0.01 kg with 2 sd limits of agreement (LOA) (0.18, -0.20). Prediction explained 88.9 % of variation but not beyond that of anthropometry. Applying these equations to the Queensland cohort provided similar performance at the appropriate age. However, when the Queensland equations were applied to our cohort, the bias increased slightly but with similar LOA. BIA appears to have limited use in predicting FFM in the first few weeks of life compared with simple anthropometry in Asian populations. There is a need for population- and age-appropriate FFM prediction equations. PMID- 26856422 TI - Early goal-directed therapy versus usual care in the management of septic shock. AB - Clinical question Does early goal-directed therapy decrease mortality when compared with usual care? Article chosen Angus DC, Barnato AE, Bell D, et al. A systematic review and meta-analysis of early goal-directed therapy for septic shock: the ARISE, ProCESS and ProMISe Investigators. Intensive Care Med 2015;41(9):1549-60. doi:10.1007/s00134-015-3822-1. PMID- 26856421 TI - Enhanced electrostatic force microscopy reveals higher-order DNA looping mediated by the telomeric protein TRF2. AB - Shelterin protein TRF2 modulates telomere structures by promoting dsDNA compaction and T-loop formation. Advancement of our understanding of the mechanism underlying TRF2-mediated DNA compaction requires additional information regarding DNA paths in TRF2-DNA complexes. To uncover the location of DNA inside protein-DNA complexes, we recently developed the Dual-Resonance-frequency Enhanced Electrostatic force Microscopy (DREEM) imaging technique. DREEM imaging shows that in contrast to chromatin with DNA wrapping around histones, large TRF2 DNA complexes (with volumes larger than TRF2 tetramers) compact DNA inside TRF2 with portions of folded DNA appearing at the edge of these complexes. Supporting coarse-grained molecular dynamics simulations uncover the structural requirement and sequential steps during TRF2-mediated DNA compaction and result in folded DNA structures with protruding DNA loops as seen in DREEM imaging. Revealing DNA paths in TRF2 complexes provides new mechanistic insights into structure-function relationships underlying telomere maintenance pathways. PMID- 26856423 TI - LASIK for Hyperopia Using an Aberration-Neutral Profile With an Asymmetric Offset Centration. AB - PURPOSE: To investigate refractive outcomes and induction of corneal higher order aberrations (HOAs) in eyes with large pupil to corneal vertex offset that underwent LASIK for hyperopia using an aberration-neutral profile with corneal vertex centration and asymmetric offset. METHODS: In this retrospective consecutive review, 26 patients (46 eyes) who underwent LASIK performed by one surgeon using the AMARIS 750S excimer laser platform and Carriazo-Pendular microkeratome (both from SCHWIND eye-tech-solutions, Kleinostheim, Germany) for flap creation were retrospectively analyzed. Only eyes targeted for plano and with a pupil to corneal vertex offset greater than 200 um were included. The preoperative metrics were correlated with the outcomes at 3 and 6 months postoperatively. RESULTS: The mean spherical equivalent was +3.43 +/- 1.30 diopters (D) preoperatively and +0.21 +/- 0.61 D at last postoperative visit (P < .0001). Mean refractive astigmatism was 1.09 +/- 1.06 D preoperatively, and 0.39 +/- 0.43 D at last postoperative visit. Postoperative uncorrected distance visual acuity of 20/25 or better was achieved in 74%, 65%, and 79% of eyes at 1, 3, and 6 months, respectively, compared to 85% corrected distance visual acuity of 20/25 or better preoperatively. Statistically significant correlation was observed between preoperative and postoperative aberration values for vertical trefoil (P < .0005), vertical coma (P < .0005), oblique tetrafoil (P < .0001), secondary cardinal astigmatism (P < .05), cardinal tetrafoil (P < .05), and secondary vertical trefoil (P < .05). CONCLUSIONS: LASIK for high levels of hyperopia using corneal vertex centration with asymmetric offset was safe and predictable. Maintaining postoperative keratometry less than 49.00 D after hyperopic LASIK and centering on corneal vertex may reduce the induction of coma compared to other profiles or centration strategies. PMID- 26856424 TI - Effects of Femtosecond Laser-Assisted Cataract Pretreatment on Pupil Diameter: A Comparison Between Three Laser Platforms. AB - PURPOSE: To assess pupil diameter before and after femtosecond laser-assisted cataract surgery (FLACS) pretreatment and compare the outcomes of three laser platforms. METHODS: This prospective observational case series included consecutive patients scheduled to undergo cataract extraction using FLACS between August 2013 and February 2015. All eyes received FLACS pretreatment using three laser platforms: LenSx (Alcon Laboratories, Inc., Fort Worth, TX), Catalys (Abbott Medical Optics Inc., Santa Ana, CA), and Victus (Bausch & Lomb, Inc., Rochester, NY). The same protocol for preoperative medical mydriasis was used for all patients, and pupil diameter was assessed immediately before and 3 minutes after FLACS using a surgical ruler. RESULTS: A total of 198 eyes of 161 patients were included in the study. Mean pupillary miosis was 1.42 +/- 1.26 mm for the LenSx, 0.66 +/- 0.89 mm for the Catalys, and 0.14 +/- 0.34 mm for the Victus groups. Furthermore, 8 of the 198 eyes (4.0%) demonstrated a pupil diameter of less than 5 mm after FLACS and 48 eyes (24.24%) demonstrated a pupil diameter of 6 mm or less. There was a statistically significant decrease in pupil diameter for all groups individually (P < .05). There was also a statistically significant difference among the three groups (P < .05), with LenSx inducing the highest degree of miosis, followed by Catalys, and finally Victus. A correlation between the pupil diameter before FLACS and degree of FLACS-induced miosis was demonstrated (P < .05), with larger pupil diameter before FLACS associated with greater miosis. CONCLUSIONS: FLACS pretreatment seems to induce significant pupillary miosis with all laser platforms assessed in this study. The decrease in pupil diameter after FLACS reached clinical significance for cataract extraction (< 5 mm) in 4.0% of cases, whereas 20.2% of eyes demonstrated small pupil diameter (<= 6 mm) after FLACS pretreatment. PMID- 26856425 TI - Pupil Influence on the Visual Outcomes of a New-Generation Multifocal Toric Intraocular Lens With a Surface-Embedded Near Segment. AB - PURPOSE: To evaluate the influences of preoperative pupil parameters on the visual outcomes of a new-generation multifocal toric intraocular lens (IOL) model with a surface-embedded near segment. METHODS: In this prospective study, patients with cataract had phacoemulsification and implantation of Lentis Mplus toric LU-313 30TY IOLs (Oculentis GmbH, Berlin, Germany). The visual and optical outcomes were measured and compared preoperatively and postoperatively. The correlations between preoperative pupil parameters (diameter and decentration) and 3-month postoperative visual outcomes were evaluated using the Spearman's rank-order correlation coefficient (Rs) for the nonparametric data. RESULTS: A total of 27 eyes (16 patients) were enrolled into the current study. Statistically significant improvements in visual and refractive performances were found after the implantation of Lentis Mplus toric LU-313 30TY IOLs (P < .05). Statistically significant correlations were present between preoperative pupil diameters and postoperative visual acuities (Rs > 0; P < .05). Patients with a larger pupil always have better postoperative visual acuities. Meanwhile, there was no statistically significant correlation between pupil decentration and visual acuities (P > .05). CONCLUSIONS: Lentis Mplus toric LU-313 30TY IOLs provided excellent visual and optical performances during the 3-month follow-up. The preoperative pupil size is an important parameter when this toric multifocal IOL model is contemplated for surgery. PMID- 26856427 TI - Correlational Analysis of Objective and Subjective Measures of Cataract Quantification. AB - PURPOSE: To evaluate whether correlations exist between objective and subjective measures of vision quality as a consequence of cataract and whether this may qualify the Objective Scatter Index as a supplementary means of cataract assessment. METHODS: A prospective multicenter, cross-sectional study was conducted in 10 centers across France in patients undergoing cataract extraction surgery (lens opacity evaluated with the Lens Opacities Classification System III). A quality of life assessment using the Visual Function Index-14 (VF-14) (14 questions scored from 0 to 4) and measurement of visual acuity and evaluation of the Objective Scatter Index (HD Analyzer, Visiometrics SL, Terrassa, Spain) to assess the alteration of light scatter were used as measures in the study. RESULTS: The study included 1,768 eyes of 1,768 patients (mean age: 72.5 years; range: 28 to 93 years). The average OSI score was 4.97 +/- 3.13 (range: 0.4 to 20.5). There was good correlation between visual acuity and OSI (r = -0.47, P < .001) and between OSI and VF-14 (r = -0.11, P < .001). CONCLUSIONS: The results presented in this study confirm that the Objective Scatter Index has sufficient correlations with visual acuity and VF-14 to supplement existing cataract diagnosis in a large population encompassing a broad spectrum of cataract presentations. PMID- 26856426 TI - Objective Scatter Index: Working Toward a New Quantification of Cataract? AB - PURPOSE: To investigate the associations between clinical cataract classifications, quality of life (QOL), and the objective loss of ocular transparency in patients presenting with clinical cataracts. METHODS: In this prospective, multicenter, cross-sectional study, 1,768 eyes of 1,768 patients (mean age: 72.5 years; range: 28 to 93 years) referred for cataract assessment were enrolled. Visual acuity was measured before slit-lamp examination to determine the severity of lens opacification using the Lens Opacities Classification System III. Patients were asked to complete the Visual Function Index (VF-14) questionnaire. Ocular transparency was quantified by Objective Scatter Index (OSI) and was measured by the HD Analyzer (Visiometrics SL, Terrassa, Spain). Association and categorical data analysis were performed between each measured parameter alongside cross-tabulation analyses to determine sensitivity and efficiency of the HD Analyzer. RESULTS: High OSI levels corresponded slightly with a lower visual acuity value and corresponded better with lower VF-14 scores. OSI scores were strongly associated with cataract classification and severity. Cross-tabulation analysis revealed a high sensitivity and efficiency index for the OSI with these clinically validated parameters illustrating good agreement overall for the OSI in determining cataract. CONCLUSIONS: The OSI measured by the HD Analyzer is a sensitive and efficient tool to be considered in the early detection of cataract in patients. PMID- 26856428 TI - Comparison of Central Corneal Thickness Between Fourier-Domain OCT, Very High Frequency Digital Ultrasound, and Scheimpflug Imaging Systems. AB - PURPOSE: To compare corneal thickness measurements between three imaging systems. METHODS: In this retrospective study of 81 virgin and 58 post-laser refractive surgery corneas, central and minimum corneal thickness were measured using optical coherence tomography (OCT), very high-frequency digital ultrasound (VHF digital ultrasound), and a Scheimpflug imaging system. Agreement between methods was analyzed using mean differences (bias) (OCT - VHF digital ultrasound, OCT - Scheimpflug, VHF digital ultrasound - Scheimpflug) and Bland-Altman analysis with 95% limits of agreement (LoA). RESULTS: Virgin cornea mean central corneal thickness was 508.3 +/- 33.2 um (range: 434 to 588 um) for OCT, 512.7 +/- 32.2 um (range: 440 to 587 um) for VHF digital ultrasound, and 530.2 +/- 32.6 um (range: 463 to 612 um) for Scheimpflug imaging. OCT and VHF digital ultrasound showed the closest agreement with a bias of -4.37 um, 95% LoA +/-12.6 um. Least agreement was between OCT and Scheimpflug imaging with a bias of -21.9 um, 95% LoA +/-20.7 um. Bias between VHF digital ultrasound and Scheimpflug imaging was -17.5 um, 95% LoA +/-19.0 um. In post-laser refractive surgery corneas, mean central corneal thickness was 417.9 +/- 47.1 um (range: 342 to 557 um) for OCT, 426.3 +/- 47.1 um (range: 363 to 563 um) for VHF digital ultrasound, and 437.0 +/- 48.5 um (range: 359 to 571 um) for Scheimpflug imaging. Closest agreement was between OCT and VHF digital ultrasound with a bias of -8.45 um, 95% LoA +/-13.2 um. Least agreement was between OCT and Scheimpflug imaging with a bias of -19.2 um, 95% LoA +/-19.2 um. Bias between VHF digital ultrasound and Scheimpflug imaging was -10.7 um, 95% LoA +/-20.0 um. No relationship was observed between difference in central corneal thickness measurements and mean central corneal thickness. Results were similar for minimum corneal thickness. CONCLUSIONS: Central and minimum corneal thickness was measured thinnest by OCT and thickest by Scheimpflug imaging in both groups. A clinically significant bias existed between Scheimpflug imaging and the other two modalities. PMID- 26856430 TI - Unilateral Post-LASIK Ectasia and Contralateral Spontaneous Ectasia. AB - PURPOSE: To report a case of iatrogenic unilateral post-LASIK corneal ectasia with contralateral spontaneous ectatic evolution. METHODS: Case report with preoperative and postoperative measurements including uncorrected visual acuity, corrected distance visual acuity, refraction, slit-scanning topographic and pachymetric maps, and differential maps. RESULTS: Six months after unilateral LASIK, the operated eye progressively developed signs of post-LASIK ectasia with increased inferior corneal steepening and corneal thinning and decrease in corrected distance visual acuity. Five years later, the unoperated eye also developed signs of spontaneous ectatic evolution with increased inferior steepening and corneal thinning. CONCLUSIONS: LASIK accelerates occurrence of ectasia in ectasia-susceptible and biomechanically fragile eyes. PMID- 26856429 TI - Corneal Molecular and Cellular Biology for the Refractive Surgeon: The Critical Role of the Epithelial Basement Membrane. AB - PURPOSE: To provide an overview of the recent advances concerning the corneal molecular and cellular biology processes involved in the wound healing response after excimer laser surface ablation and LASIK surgery. METHODS: Literature review. RESULTS: The corneal wound healing response is a complex cascade of events that impacts the predictability and stability of keratorefractive surgical procedures such as photorefractive keratectomy and LASIK. The generation and persistence of corneal myofibroblasts (contractile cells with reduced transparency) arise from the interaction of cytokines and growth factors such as transforming growth factor beta and interleukin 1 produced by epithelial and stromal cells in response to the corneal injury. Myofibroblasts, and the opaque extracellular matrix they secrete into the stroma, disturb the precise distribution and spacing of collagen fibers related to corneal transparency and lead to the development of vision-limiting corneal opacity (haze). The intact epithelial basement membrane has a pivotal role as a structure that regulates corneal epithelial-stromal interactions. Thus, defective regeneration of the epithelial basement membrane after surgery, trauma, or infection leads to the development of stromal haze. The apoptotic process following laser stromal ablation, which is proportional to the level of attempted correction, leads to an early decrease in anterior keratocyte density and the diminished contribution of these non-epithelial cells of components such as perlecan and nidogen-2 required for normal regeneration of the epithelial basement membrane. Haze persists until late repair of the defective epithelial basement membrane. CONCLUSIONS: Defective regeneration of the epithelial basement membrane has a critical role in determining whether a cornea heals with late haze after photorefractive keratectomy or with scarring at the flap edge in LASIK. PMID- 26856431 TI - Femtosecond Laser-Assisted Cataract Surgery in Phakic Intraocular Lens With Cataract. AB - PURPOSE: To report two cases of cataract with phakic intraocular lens (PIOL) in situ that underwent femtosecond laser-assisted cataract surgery (FLACS) along with PIOL explantation. METHODS: Case reports. RESULTS: The first case had an implantable collamer lens (ICL) in situ. A well-centered, circular femtosecond laser capsulotomy was achieved. Incomplete nucleotomy was noted due to the entrapment of cavitation bubbles beneath the ICL. Postoperative visual acuity was 20/20. The second case had a rigid iris-claw PIOL in situ. Successful femtosecond laser-assisted capsulotomy and nuclear fragmentation were achieved. The PIOL was disenclavated temporally and displaced inferiorly followed by completion of phacoemulsification. The PIOL was explanted at the end of surgery by enlarging the temporal incision. Postoperative uncorrected visual acuity was 20/32. CONCLUSIONS: The femtosecond laser can be used to create a capsulotomy and nuclear fragmentation through both anterior and posterior chamber PIOLs. PMID- 26856432 TI - Erratum for "Evaluation of Uva Cytotoxicity for Human Endothelium in an Ex Vivo Corneal Cross-Linking Experimental Setting". PMID- 26856433 TI - Managing Descemet Detachment in Femtosecond Laser-Assisted Cataract Surgery: The Isolate-and-Release Technique. PMID- 26856434 TI - Long-term Outcomes of Flap Amputation After LASIK. PMID- 26856435 TI - Intraoperative Aberrometry and Intraocular Lens Power Calculation. PMID- 26856436 TI - Intracorneal Inlays. PMID- 26856438 TI - Comparing Luminex NxTAG-Respiratory Pathogen Panel and RespiFinder-22 for multiplex detection of respiratory pathogens. AB - Respiratory tract infection (RTI) involves a variety of viruses and bacteria, which can be conveniently detected by multiplex nucleic acid amplification testing (NAT). To compare the novel Luminex-based NxTAG-Respiratory Pathogen Panel (NxTAG-RPP) with the routine multiplex-ligation-NAT based RespiFinder-22(r) (RF-22), 282 respiratory specimens including nasopharyngeal swabs (71%), broncho alveolar lavage (27%), throat swabs, tracheal secretions, and sputum (2%) from 116 children and 155 adults were extracted using a Corbett CAS1200 (Qiagen), and analyzed in parallel by the routine RF-22 and NxTAG-RPP. Concordant results were obtained in 263 (93.3%) cases consisting of concordant positives in 167 (59.2%) and concordant negatives in 96 (34%). Results were discordant in 19 (6.7%) consisting of 15 positive:negative, and 4 negative:positive results by NxTAG-RPP versus RF-22, respectively. Co-infections were observed in 10.3% with NxTAG-RPP and in 5.9% with RF-22. Most additional viral pathogens identified by the NxTAG RPP involved dual infections with rhinovirus and RSV. Discordant samples were mainly due to low genome signals of Ct less than 36, when retested by QNAT suggesting a higher sensitivity of the NxTAG-RPP, also when detecting multiple infections. Hands-on time after extraction for 24 and 96 samples was 0.25 and <0.5 hr for the NxTAG-RPP, and 2 and 4 hr for the RF-22, respectively. The median turn-around time was 6 hr (range 5-7 hr) for NxTAG-RPP and 12 hr (range 8-16 hr) for RF-22. The NxTAG-RPP showed comparable detection rates for most respiratory pathogens, while hands-on and turn-around time were considerably shorter. The clinical significance of detecting multiple viruses needs further clinical evaluation. J. Med. Virol. 88:1319-1324, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26856437 TI - Integrated analysis of the involvement of nitric oxide synthesis in mitochondrial proliferation, mitochondrial deficiency and apoptosis in skeletal muscle fibres. AB - Nitric oxide (NO) is an important signaling messenger involved in different mitochondrial processes but only few studies explored the participation of NO in mitochondrial abnormalities found in patients with genetic mitochondrial deficiencies. In this study we verified whether NO synthase (NOS) activity was altered in different types of mitochondrial abnormalities and whether changes in mitochondrial function and NOS activity could be associated with the induction of apoptosis. We performed a quantitative and integrated analysis of NOS activity in individual muscle fibres of patients with mitochondrial diseases, considering mitochondrial function (cytochrome-c-oxidase activity), mitochondrial content, mitochondrial DNA mutation and presence of apoptotic nuclei. Our results indicated that sarcolemmal NOS activity was increased in muscle fibres with mitochondrial proliferation, supporting the relevance of neuronal NOS in the mitochondrial biogenesis process. Sarcoplasmic NOS activity was reduced in cytochrome-c-oxidase deficient fibres, probably as a consequence of the involvement of NO in the regulation of the respiratory chain. Alterations in NOS activity or mitochondrial abnormalities were not predisposing factors to apoptotic nuclei. Taken together, our results show that NO can be considered a potential molecular target for strategies to increase mitochondrial content and indicate that this approach may not be associated with increased apoptotic events. PMID- 26856440 TI - Clinical Characteristics and Outcomes of Older Cardiac Resynchronization Therapy Recipients Using a Pacemaker versus a Defibrillator. AB - BACKGROUND: Cardiac resynchronization therapy (CRT) is commonly used to manage heart failure, yet published guidelines do not distinguish between recommendations for pacemakers (CRT-P) and defibrillators (CRT-D) despite significant differences in size, longevity, and cost between these devices. The purpose of this study is to compare the clinical characteristics and outcomes between elderly recipients of CRT-P and CRT-D. METHODS AND RESULTS: Data from 512 patients (405 CRT-D, 107 CRT-P) aged >=75 years with LV ejection fraction <=35% and QRS duration >120 milliseconds were retrospectively analyzed for baseline characteristics and followed to the primary outcome of all-cause mortality. Cox proportional hazards models were used to adjust for possible confounders. Results were further validated through propensity matching cohorts. Compared to CRT-D recipients, CRT-P patients were older (83 years vs. 81 years, P < 0.001) and had more comorbid conditions (Charlson index = 5 [3-6] vs. 4 [3-5], P = 0.007). During 40.8 months of follow-up, there were 280 deaths. Compared to CRT-D patients, CRT-P recipients had higher unadjusted mortality (HR 1.54, 95% CI 1.15 2.08, P = 0.004). However, this difference lost significance after adjusting for baseline differences between the groups (HR 1.18, 95% CI 0.78-1.77, P = 0.435). CONCLUSION: Higher all-cause mortality in older CRT-P versus CRT-D patients is largely explained by baseline clinical and demographic differences between the two groups, which are likely the drivers of device selection in real-world clinical practice, where the published guidelines remain ambiguous. There is a need for randomized studies to determine optimal CRT device selection. PMID- 26856441 TI - Translational and clinical research highlights from the 38th San Antonio Breast Cancer Symposium. AB - 38th San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 8-12 December 2015. In November 1978, during Breast Cancer Awareness Week, the first annual San Antonio Breast Cancer Symposium (SABCS) was held as a part of an educational program conceived to reduce breast cancer death rate. Only 141 physicians attended the conference. Recently, the 38th edition of the SABCS welcomed >7000 attendees from all over the world. We will discuss a selection of the most significant advances presented at the 2015 SABCS, specifically focusing on those data that could have an impact on the clinical practice in the near future. PMID- 26856439 TI - The Prevalence and Molecular Epidemiology of Multidrug-Resistant Enterobacteriaceae Colonization in a Pediatric Intensive Care Unit. AB - OBJECTIVE: To determine the prevalence and acquisition of extended-spectrum beta lactamases (ESBLs), plasmid-mediated AmpCs (pAmpCs), and carbapenemases ("MDR Enterobacteriaceae") colonizing children admitted to a pediatric intensive care unit (PICU). DESIGN: Prospective study. SETTING: 40-bed PICU. METHODS: Admission and weekly thereafter rectal surveillance swabs were collected on all pediatric patients during a 6-month study period. Routine phenotypic identification and antibiotic susceptibility testing were performed. Enterobacteriaceae displaying characteristic resistance profiles underwent further molecular characterization to identify genetic determinants of resistance likely to be transmitted on mobile genetic elements and to evaluate relatedness of strains including DNA microarray, multilocus sequence typing, repetitive sequence-based PCR, and hsp60 sequencing typing. RESULTS: Evaluating 854 swabs from unique children, the overall prevalence of colonization with an MDR Enterobacteriaceae upon admission to the PICU based on beta-lactamase gene identification was 4.3% (n=37), including 2.8% ESBLs (n=24), 1.3% pAmpCs (n=11), and 0.2% carbapenemases (n=2). Among 157 pediatric patients contributing 603 subsequent weekly swabs, 6 children (3.8%) acquired an incident MDR Enterobacteriaceae during their PICU stay. One child acquired a pAmpC (E. coli containing bla DHA) related to an isolate from another patient. CONCLUSIONS: Approximately 4% of children admitted to a PICU were colonized with MDR Enterobacteriaceae (based on beta-lactamase gene identification) and an additional 4% of children who remained in the PICU for at least 1 week acquired 1 of these organisms during their PICU stay. The acquired MDR Enterobacteriaceae were relatively heterogeneous, suggesting that a single source was not responsible for the introduction of these resistance mechanisms into the PICU setting. PMID- 26856442 TI - Physical and chemical evaluation of furniture waste briquettes. AB - Furniture waste is mainly composed of wood and upholstery foam (mostly polyurethane foam). Both of these have a high calorific value, therefore, energy recovery would be an appropriate process to manage these wastes. Nevertheless, the drawback is that the energy content of these wastes is limited due to their low density mainly that of upholstery foam. Densification of separate foam presents difficulties due to its elastic character. The significance of this work lies in obtaining densified material by co-densification of furniture wood waste and polyurethane foam waste. Densification of furniture wood and the co densification of furniture wood waste with polyurethane foam have been studied. On the one hand, the parameters that have an effect on the quality of the furniture waste briquettes have been analysed, i.e., moisture content, compaction pressure, presence of lignin, etc. The maximum weight percentage of polyurethane foam that can be added with furniture wood waste to obtain durable briquettes and the optimal moisture were determined. On the other hand, some parameters were analysed in order to evaluate the possible effect on the combustion. The chemical composition of waste wood was compared with untreated wood biomass; the higher nitrogen content and the concentration of some metals were the most important differences, with a significant difference of Ti content. PMID- 26856443 TI - Assessment of protease activity in hydrolysed extracts from SSF of hair waste by and indigenous consortium of microorganisms. AB - Hair wastes from the tannery industry were assessed for its suitability as substrates for protease production by solid-state fermentation (SSF) using a pilot-batch mode operation and anaerobically digested sludge as co-substrate. Maximum protease activity (52,230+/-1601 U g(-1) DM) was observed at the 14th day of SSF. Single step purification resulted in 2 fold purification with 74% of recovery by ultrafiltration with 10 kDa cut-off. The recovered enzyme was stable at a temperature of 30 degrees C and pH 11; optimal conditions that were determined by a central composite full factorial experimental design. The enzyme activity was inhibited by phenylmethylsulfonyl fluoride, which indicates that it belongs to serine protease group. The remaining solid material after protease extraction could be easily stabilized to obtain a final good quality compost-like material as the final dynamic respiration index was lower than 1 g O2 kg(-1) OM h(-1). The lyophilized recovered enzymes were a good alternative in the process of cowhides dehairing with respect to the current chemical treatment, avoiding the production of solid wastes and highly polluted wastewaters. In conclusion, the entire process can be considered a low-cost sustainable technology for the dehairing process, closing the organic matter cycle in the form of value added product and a compost-like material from a waste. PMID- 26856444 TI - Production of activated carbons from waste tyres for low temperature NOx control. AB - Waste tyres were pyrolysed in a bench scale reactor and the product chars were chemically activated with alkali chemical agents, KOH, K2CO3, NaOH and Na2CO3 to produce waste tyre derived activated carbons. The activated carbon products were then examined in terms of their ability to adsorb NOx (NO) at low temperature (25 degrees C) from a simulated industrial process flue gas. This study investigates the influence of surface area and porosity of the carbons produced with the different alkali chemical activating agents on NO capture from the simulated flue gas. The influence of varying the chemical activation conditions on the porous texture and corresponding NO removal from the flue gas was studied. The activated carbon sorbents were characterized in relation to BET surface area, micropore and mesopore volumes and chemical composition. The highest NO removal efficiency for the waste tyre derived activated carbons was ~75% which was obtained with the adsorbent treated with KOH which correlated with both the highest BET surface area and largest micropore volume. In contrast, the waste tyre derived activated carbons prepared using K2CO3, NaOH and Na2CO3 alkali activating agents appeared to have little influence on NO removal from the flue gases. The results suggest problematic waste tyres, have the potential to be converted to activated carbons with NOx removal efficiency comparable with conventionally produced carbons. PMID- 26856445 TI - High performance of treated and washed MSWI bottom ash granulates as natural aggregate replacement within earth-moist concrete. AB - Municipal solid waste incineration bottom ash was treated with specially designed dry and wet treatment processes, obtaining high quality bottom ash granulate fractions (BGF) suitable for up to 100% replacement of natural gravel in concrete. The wet treatment (using only water for separating and washing) significantly lowers the leaching of e.g. chloride and sulfate, heavy metals (antimony, molybdenum and copper) and dissolved organic carbon (DOC). Two potential bottom ash granulate fractions, both in compliance with the standard EN 12620 (aggregates for concrete), were added into earth-moist concrete mixtures. The fresh and hardened concrete physical performances (e.g. workability, strength and freeze-thaw) of high strength concrete mixtures were maintained or improved compared with the reference mixtures, even after replacing up to 100% of the initial natural gravel. Final element leaching of monolithic and crushed granular state BGF containing concretes, showed no differences with the gravel references. Leaching of all mixtures did not exceed the limit values set by the Dutch Soil Quality Degree. In addition, multiple-life-phase emission (pH static test) for the critical elements of input bottom ash, bottom ash granulate (BGF) and crushed BGF containing concrete were assessed. Simulation pH lowering or potential carbonation processes indicated that metal (antimony, barium, chrome and copper) and sulfate element leaching behavior are mainly pH dominated and controlled, although differ in mechanism and related mineral abundance. PMID- 26856446 TI - Comparison of the organic waste management systems in the Danish-German border region using life cycle assessment (LCA). AB - This study assessed the management of the organic household waste in the Danish German border region and points out major differences between the systems and their potential effects on the environment using life cycle assessment (LCA). The treatment of organic waste from households in the Danish-German border region is very different on each side of the border; the Danish region only uses incineration for the treatment of organic household waste while the German region includes combined biogas production and composting, mechanical and biological treatment (MBT) and incineration. Data on all parts of the organic waste treatment was collected including waste composition data and data from treatment facilities and their respective energy systems. Based on that the organic waste management systems in the border region were modelled using the EASETECH waste management LCA-model. The main output is a life cycle assessment showing large differences in the environmental performance of the two different regions with the Danish region performing better in 10 out of 14 impact categories. Furthermore, the importance of the substituted district heating systems was investigated showing an impact up to 34% of the entire system for one impact category and showing large difference between each heating system substituted, e.g. in "Global Warming" the impact was from -16 to -1.1 milli person equivalent/tonne treated waste from substitution of centralised hard coal and decentralised natural gas, respectively. PMID- 26856447 TI - Decontamination of CCA-treated eucalyptus wood waste by acid leaching. AB - Preservatives such as chromated copper arsenate (CCA) are used to increase the resistance of wood to deterioration. The components of CCA are highly toxic, resulting in growing concern over the disposal of the waste generated. The aim of this study was to investigate the removal of Cu, Cr and As present in CCA-treated eucalyptus wood from utility poles removed from service in southern Brazil, in order to render them non-hazardous waste. The removal was carried out by acid leaching in bench-scale and applying optimal extractor concentration, total solid content, reactor volume, temperature and reaction time obtained by factorial experiments. The best working conditions were achieved using three extraction steps with 0.1 mol L(-1) H2SO4 at 75 degrees C for 2h each (total solid content of 15%), and 3 additional 1h-long washing steps using water at ambient temperature. Under these conditions, removal of 97%, 85% and 98% were obtained for Cu, Cr and As, respectively, rendering the decontaminated wood non-hazardous waste. The wastewater produced by extraction showed acid pH, high organic loading as well as high concentrations of the elements, needing prior treatment to be discarded. However, rinsing water can be recycled in the extraction process without compromising its efficiency. The acid extraction is a promising alternative for CCA removal from eucalyptus wood waste in industrial scale. PMID- 26856448 TI - Identification of genes differentially expressed during early interactions between the stem rot fungus (Sclerotium rolfsii) and peanut (Arachis hypogaea) cultivars with increasing disease resistance levels. AB - Sclerotium rolfsii, a destructive soil-borne fungal pathogen causes stem rot of the cultivated peanut, Arachis hypogaea. This study aimed to identify differentially expressed genes associated with peanut resistance and fungal virulence. Four peanut cultivars (A100-32, Georgia Green, GA-07W and York) with increasing resistance levels were inoculated with a virulent S. rolfsii strain to study the early plant-pathogen interaction. 454 sequencing was performed on RNAs from infected tissue collected at 4 days post inoculation, generating 225,793 high-quality reads. Normalized read counts and fold changes were calculated and statistical analysis used to identify differentially expressed genes. Several genes identified as differential in the RNA-seq experiment were selected based on functions of interest and real-time PCR employed to corroborate their differential expression. Expanding the analysis to include all four cultivars revealed a small but interesting set of genes showing colinearity between cultivar resistance and expression levels. This study identified a set of genes possibly related to pathogen response that may be useful marker assisted selection or transgenic disease control strategies. Additionally, a set of differentially expressed genes that have not been functionally characterized in peanut or other plants and warrant additional investigation were identified. PMID- 26856449 TI - Enhancement of drought stress tolerance in crops by plant growth promoting rhizobacteria. AB - Drought is one of the major constraints on agricultural productivity worldwide and is likely to further increase. Several adaptations and mitigation strategies are required to cope with drought stress. Plant growth promoting rhizobacteria (PGPR) could play a significant role in alleviation of drought stress in plants. These beneficial microorganisms colonize the rhizosphere/endo-rhizosphere of plants and impart drought tolerance by producing exopolysaccharides (EPS), phytohormones, 1-aminocyclopropane- 1-carboxylate (ACC) deaminase, volatile compounds, inducing accumulation of osmolytes, antioxidants, upregulation or down regulation of stress responsive genes and alteration in root morphology in acquisition of drought tolerance. The term Induced Systemic Tolerance (IST) was coined for physical and chemical changes induced by microorganisms in plants which results in enhanced tolerance to drought stresses. In the present review we elaborate on the role of PGPR in helping plants to cope with drought stress. PMID- 26856450 TI - The new flagella-associated collagen-like proteins ClpB and ClpC of Bacillus amyloliquefaciens FZB42 are involved in bacterial motility. AB - Collagen-like proteins (CLPs) share the distinctive Gly-X-Thr repeating amino acid sequence of animal collagens, and contain N- and C-terminal domain making a collagen-like structure in Bacillus amyloliquefaciens FZB42, a plant growth promoting rhizobacterium. Our previous study demonstrated that CLPs play important roles in biofilm construction and adherence to the surfaces on plant roots. However, bacterial localization of the CLPs remains unclear. Here, disrupted strains on all four clp genes (clpA, clpB, clpC and clpD) shown fewer filament than wild-type bacteria in extracellular matrix under scanning electron microscope (SEM). Transmission electron microscopy (TEM) was used to observe the differences on filament which associated on the cell surface, then the CLPs mutation strains showed less flagella than the wild type. Immunogold labeling determined the location that ClpB and ClpC localized on the flagella surface. In addition, western blotting analysis of crude flagella extracts suggested that the ClpB and ClpC are associated to flagella as well. The mutation strains also reduced motility of swimming on the surface of soft agar medium and changed the architectural of microcolony biofilm edge. The study suggests that collagen-like protein ClpB and ClpC, as novel proteins, associated with flagella in B. amyloliquefaciens. PMID- 26856452 TI - The degradation of RcsA by ClpYQ(HslUV) protease in Escherichia coli. AB - In Escherichia coli, RcsA, a positive activator for transcription of cps (capsular polysaccharide synthesis) genes, is degraded by the Lon protease. In lon mutant, the accumulation of RcsA leads to overexpression of capsular polysaccharide. In a previous study, overproduction of ClpYQ(HslUV) protease represses the expression of cpsB?lacZ, but there has been no direct observation demonstrating that ClpYQ degrades RcsA. By means of a MBP-RcsA fusion protein, we showed that RcsA activated cpsB?lacZ expression and could be rapidly degraded by Lon protease in SG22622 (lon(+)). Subsequently, the comparative half-life experiments performed in the bacterial strains SG22623 (lon) and AC3112 (lon clpY clpQ) indicated that the RcsA turnover rate in AC3112 was relatively slow and RcsA was stable at 30 degrees C or 41 degrees C. In addition, ClpY could interact with RscA in an in vitro pull-down assay, and the more rapid degradation of RcsA was observed in the presence of ClpYQ protease at 41 degrees C. Thus, we conclude that RcsA is indeed proteolized by ClpYQ protease. PMID- 26856453 TI - Reduction in cardiovascular and all-cause mortality in the EMPA-REG OUTCOME trial: A critical analysis. PMID- 26856451 TI - Efficacies of quorum sensing inhibitors, piericidin A and glucopiericidin A, produced by Streptomyces xanthocidicus KPP01532 for the control of potato soft rot caused by Erwinia carotovora subsp. atroseptica. AB - To discover potential inhibitors of the quorum sensing (QS) system, a library of microbial culture extracts was screened with Chromobacterium violaceumCV026 strain. The culture extract of Streptomyces xanthocidicus KPP01532 contained quorum-sensing inhibitors (QSIs) of the CV026 strain. The active constituents of the culture extract of strain KPP01532 were purified using a series of chromatographic procedures, and based on data from NMR and mass spectroscopy, piericidin A and glucopiericidin A were identified. Erwinia carotovora subsp. atroseptica (Eca) is a plant pathogen that causes blackleg and soft rot diseases on potato stems and tubers. The virulence factors of Eca are regulated by QS. The expression of virulence genes (pelC, pehA, celV and nip) under the control of QS was monitored using quantitative real-time PCR (qRT-PCR). The transcription levels of the four genes were significantly lower when Eca was exposed to piericidin A or glucopiericidin A. These two compounds displayed similar control efficacies against soft rot caused by Eca in potato slices as furanone C-30. Therefore, piericidin A and glucopiericidin A are potential QSIs that suppress the expression of the virulence genes of Eca, suggesting that they could have potential use as control agents of soft rot disease on potato tubers. PMID- 26856454 TI - Effect of immediate and delayed dentin sealing on the fracture strength, failure type and Weilbull characteristics of lithiumdisilicate laminate veneers. AB - OBJECTIVES: Adhesion on dentin is less reliable than on enamel, which could affect the durability of laminate veneers (LV). Immediate dentin sealing (IDS) is suggested instead of delayed dentin sealing (DDS) to overcome hypersensitivity and prevent debonding from dentin. This study evaluated the effect of IDS and DDS on the durability of Li2Si2O5 laminate veneers in vitro. METHODS: Window preparations were made on the labial surfaces of sound maxillary central incisors (N=50). They were randomly divided into five groups: Group 1: Enamel only+H3PO4+Adhesive (control); Group 2: <1/4 dentin+H3PO4+DDS (2 weeks later); Group 3: Complete dentin+H3PO4+DDS (2 weeks later); Group 4: <1/4 dentin+H3PO4+IDS; Group 5: Complete dentin+H3PO4+IDS. Li2Si2O5 laminate veneers (e.max Press) were bonded to the labial surfaces of the teeth with adhesive resin cement (Variolink Veneer). IDS layers were silicacoated (CoJet System) and silanized (ESPE-Sil). The teeth with their bonded laminates were thermocycled (10.000* cycles) and then subjected to static loading (1mm/min). Failure type and location after debonding were classified. Data were analyzed using ANOVA and Tukey's post hoc test (alpha=0.05). Two-parameter Weibull distribution values including the Weibull modulus, scale (m) and shape (0), values were calculated. RESULTS: Mean fracture strength (N) per group in descending order was as follows: Group 5 (576+/-254), Group 4 (478+/-216), Group 1 (473+/-159), Group 2 (465+/ 186), and Group 3 (314+/-137). The presence of complete dentin exposure sealed with DDS after 2 weeks on the bonded surface (Group 3) resulted in significantly lower fracture strength results than those in group 5 with IDS (p=0.034). Weibull distribution presented higher shape (0) for Group 1 (3.67), than those of other groups (2.51-2.89). Failure types were predominantly adhesive failure between the cement and the laminate veneer in Groups 1, 2, 4 whereas Group 3 presented more often complete adhesive failures between the cement and dentin. In Group 5, failures showed some IDS and cement with or without ceramic fracture attached on the tooth. SIGNIFICANCE: When laminate veneers are bonded to a large dentin substrate, application of immediate dentin sealing improves adhesion and thereby, the fracture strength of Li2Si2O5 laminate veneers. PMID- 26856455 TI - Genetic analysis of DACT1 in 100 Chinese Han women with Mullerian duct anomalies. AB - Dapper antagonist of catenin-1 (DACT1) plays an important role in embryogenesis and organogenesis of the female reproductive tract in mouse models. The aim of this study was to investigate the association between DACT1 mutations and human Mullerian duct anomalies (MDA). One hundred clinically well-defined Chinese Han patients with MDA and 200 healthy controls were recruited in this study. All four exons coding for DACT1 were amplified and sequenced. A missense mutation (c.G1084A, p.V362M) was identified in a patient who had a didelphic uterus and was absent from the control group. This variant changed the hydrophilicity of the amino acid residue and was predicted to be deleterious to the structure and function of DACT1 protein. The data indicate that the p.V362M mutation of DACT1 may be an underlying cause of MDA. PMID- 26856456 TI - Exploiting non-linear relationships between retention time and molecular structure of peptides originating from proteomes and comparing three multivariate approaches. AB - Peptides' retention time prediction is gaining increasing popularity in liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics. This is a promising approach for improving successful proteome mapping, useful both in identification and quantification workflows. In this work, a quantitative structure-retention relationships (QSRR) model for its direct prediction from the molecular structure of 185 peptides originating from 8 well-characterized proteins and two Bacillus subtilis proteomes has been developed. Genetic Algorithm (GA) was used for selection of a subset of molecular descriptors coupled with three machine learning methods: Support Vector Regression (SVR), Artificial Neural Networks (ANN), and kernel Partial Least Squares (kPLS) for regression. Final GA-SVR, GA-ANN, and GA-kPLS models were validated through an external validation set of 95 peptides originating from the human epithelial HeLa cells proteomes. Robustness and stability was ensured by defining their applicability domain. The descriptors of the developed models were interpreted confirming a causal relationship between parameters of molecular structure and retention time. GA-SVR model has shown to be superior over the others in terms of both predictive ability, and interpretation of the selected descriptors. PMID- 26856457 TI - Surface plasmon resonance and circular dichroism characterization of cucurbitacins binding to serum albumins for early pharmacokinetic profiling. AB - Cucurbitacins are a group of tetracyclic triterpenoids, known for centuries for their anti-cancer and anti-inflammatory properties, which are being actively investigated over the past decades in order to elucidate their mechanism of action. In perspective of being used as therapeutic molecules, a pharmacokinetic characterization is crucial to assess the affinity toward blood carrier proteins and extrapolate distribution volumes. Usually, pharmacokinetic data are first collected on animal models and later translated to humans; therefore, an early characterization of the interaction with carrier proteins from different species is highly desirable. In the present study, the interactions of cucurbitacins E and I with human and rat serum albumins (HSA and RSA) were investigated by means of surface plasmon resonance (SPR)-based optical biosensing and circular dichroism (CD) spectroscopy. Active HSA and RSA sensor chip surfaces were prepared through an amine coupling reaction protocol, and the equilibrium dissociation constants (Kd) for the different cucurbitacins-serum albumins complexes were then determined by SPR analysis. Further information on the binding of cucurbitacins to serum albumins was obtained by CD competition experiments with biliverdin, a specific marker binding to subdomain IB of HSA. SPR data unveiled a previously unreported binding event between CucI and HSA; the determined binding affinities of both compounds were slightly higher for RSA with respect to HSA, even though all the compounds can be ranked as high-affinity binders for both carriers. CD analysis showed that the two cucurbitacins modify the binding of biliverdin to serum albumins through opposite allosteric modulation (positive for HSA, negative for RSA), confirming the need for caution in the translation of pharmacokinetic data across species. PMID- 26856458 TI - Aneurysm Organization Effects of Gellan Sulfate Core Platinum Coil with Tenascin C in a Simulated Clinical Setting and the Possible Mechanism. AB - BACKGROUND: This study aimed to deliver gellan sulfate core platinum coil with tenascin-C (GSCC-TNC) into rabbit side-wall aneurysms endovascularly and to evaluate the organization effects in a simulated clinical setting. METHODS: Elastase-induced rabbit side-wall aneurysms were randomly coiled via a transfemoral route like clinical settings with platinum coils (PCs), gellan sulfate core platinum coils (GSCCs), or GSCC-TNCs (n = 5, respectively). Aneurysm occlusion status was evaluated angiographically and histologically at 2 weeks post coiling. As each rabbit coiled aneurysm provided only 2-3 tissue slices due to technical limitations and prevented immunohistochemical evaluations, a PC, GSCC, or GSCC-TNC was randomly implanted in a rat blind-ended model (n = 3, respectively) and the organization effects were immunohistochemically evaluated for expressions of tenascin-C (TNC), transforming growth factor-beta (TGF-beta), and matrix metalloproteinase-9 (MMP-9) 2 weeks later. RESULTS: Coil handling was similar among the 3 kinds of coils. GSCCs showed a significantly higher ratio of organized area to the aneurysmal cavity than PCs, but GSCC-TNCs had the greatest organization-promoting effects on aneurysms (the ratio of organized area/aneurysmal luminal area: PC, 17.9 +/- 7.1%; GSCC, 54.2 +/- 18.3%; GSCC-TNC, 82.5 +/- 5.8%). GSCC-TNCs had intense immunoreactivities for TNC, TGF-beta, and MMP-9 in the organized thrombosis and tunica media. GSCCs also showed intense immunoreactivities for TNC, TGF-beta, and MMP-9, although the extent was less than GSCC-TNCs. The immunoreactivities were hardly found in unorganized thrombus and the tunica media of aneurysm wall in the PC group. CONCLUSIONS: This study first showed that GSCC-TNCs promote intra-aneurysmal clot organization in simulated clinical settings using rabbits possibly through the TGF-beta and MMP-9 upregulation. PMID- 26856459 TI - A Retrospective Cohort Study on the Use of Intravenous Thrombolysis in Stroke Mimics. AB - BACKGROUND: The urgency of intravenous thrombolysis in acute ischemic stroke can lead to inadvertent thrombolysis of patients with nonstroke diagnoses (stroke mimics), increasing the risk of adverse events. The objectives of this study were to compare thrombolysed acute ischemic stroke and stroke mimic cases based on demographic factors, physiological parameters, radiological findings, and clinical presentation, and to evaluate the clinical implications of thrombolysing stroke mimics. METHODS: A retrospective analysis of a single-center database of all thrombolysed strokes and mimics over a period greater than 3 years. Diagnoses were confirmed by expert consensus after a review of clinical factors and imaging. Intercohort variation was assessed using Wilcoxon rank-sum or Pearson's chi-square test. RESULTS: The stroke mimic cohort tended to be younger (mean age 59.9 years versus 73.7 years, P < .001) and had a lower National Institutes of Health Stroke Score at presentation (mean 5.9 points versus 6.4 points, P < .01). However, the time taken from the onset of symptoms to delivery of thrombolytic drugs was longer in the mimic cohort (mean time 170 minutes versus 138 minutes, P < .01). Any differences in blood glucose (P = .07), time taken from hospital arrival to delivery of intravenous thrombolysis (P = .57), and blood pressure on admission (systolic, P = .09 and diastolic, P = .34) were not statistically significant. No adverse events were reported in the mimic cohort. CONCLUSION: Despite similarities in clinical presentation, thrombolysed stroke mimics are of a different physiological and demographic population, and are associated with fewer adverse events compared with thrombolysed acute ischemic stroke patients. PMID- 26856460 TI - Successful Use of Intravenous Tissue Plasminogen Activator as Treatment for a Patient with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: A Case Report and Review of Literature. AB - BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is considered a common cause of hereditary stroke caused by mutation of the NOTCH3 gene. Evidence against the use of intravenous tissue plasminogen activator (IV tPA) has been suggested due to possibility of hemorrhage. We present a case of a patient with CADASIL who was successfully treated using IV tPA. METHODS: A case description of a female patient who presented with stroke-like symptoms was a previously known case of CADASIL. Review of literature was done using search terms such as CADASIL, NOTCH3, and intracranial hemorrhage or brain hemorrhage. RESULTS: A 35-year-old female patient presented to the emergency department with acute onset hemiparesis, hemiparesthesia, and motor aphasia with a National Institutes of Health Stroke Scale score of 8. The patient was a previously diagnosed case of CADASIL with a positive NOTCH3 mutation. Computed tomography scan showed no large vessel occlusion with no perfusion deficient. Patient was within window for IV tPA treatment which was administered, and she subsequently had marked improvement of all symptoms. CONCLUSION: There is slight evidence against the use of IV tPA for CADASIL patients who present with stroke-like symptoms but nothing is concrete. It has also been suggested that some patients who are undiagnosed have been treated with IV tPA with favorable results but unfortunately are not reported. Further studies and or large clinical trials could be beneficial for those patients who may benefit from IV tPA and who have previously been diagnosed with CADASIL. PMID- 26856461 TI - Antiplatelet Agents for the Secondary Prevention of Ischemic Stroke or Transient Ischemic Attack: A Network Meta-Analysis. AB - Stroke can cause high morbidity and mortality, and ischemic stroke (IS) and transient ischemic attack (TIA) patients have a high stroke recurrence rate. Antiplatelet agents are the standard therapy for these patients, but it is often difficult for clinicians to select the best therapy from among the multiple treatment options. We therefore performed a network meta-analysis to estimate the efficacy of antiplatelet agents for secondary prevention of recurrent stroke. We systematically searched 3 databases (PubMed, Embase, and Cochrane) for relevant studies published through August 2015. The primary end points of this meta analysis were overall stroke, hemorrhagic stroke, and fatal stroke. A total of 30 trials were included in our network meta-analysis and abstracted data. Among the therapies evaluated in the included trials, the estimates for overall stroke and hemorrhagic stroke for cilostazol (Cilo) were significantly better than those for aspirin (odds ratio [OR] = .64, 95% credibility interval [CrI], .45-.91; OR = .23, 95% CrI, .08-.58). The estimate for fatal stroke was highest for Cilo plus aspirin combination therapy, followed by Cilo therapy. The results of our meta analysis indicate that Cilo significantly improves overall stroke and hemorrhagic stroke in IS or TIA patients and reduces fatal stroke, but with low statistical significance. Our results also show that Cilo was significantly more efficient than other therapies in Asian patients; therefore, future trials should focus on Cilo treatment for secondary prevention of recurrent stroke in non-Asian patients. PMID- 26856463 TI - Analysis of Association between MAP2K4 Gene Polymorphism rs3826392 and IL-1b Serum Level in Southern Chinese Han Ischemic Stroke Patients. AB - BACKGROUND: Mitogen-activated protein kinase kinase 4 (MAP2K4) gene acts as the direct upstream activator of c-Jun NH2-terminal kinase pathway, which plays an important role in regulating neuron survival and apoptosis in response to cerebral ischemia. However, the association between MAP2K4 gene polymorphisms and ischemic stroke (IS) has not yet been published. Therefore, this study investigates the association between MAP2K4 gene polymorphism rs3826392 and IS susceptibility, as well as its quantitative traits in Southern Chinese Han population. METHODS: A total of 816 Chinese patients with IS and 816 age- and sex matched controls were recruited. Rs3826392 was genotyped using Sequenom MassARRAY iPLEX platform (Sequenom, San Diego, CA, USA). The mRNA expression of MAP2K4 gene in peripheral blood mononuclear cells was detected using reverse transcription polymerase chain reaction. The levels of serum cytokines, including IL-1b, IL-6, IL-8, IL-12, and tumor necrosis factor-alpha (TNF-alpha), were measured by enzyme linked immunosorbent assay. RESULTS: Significant association was not observed between MAP2K4 gene polymorphism rs3826392 and IS susceptibility in all genetic models (P > .05). A significant difference was found in IL-1b, IL-6, IL-8, and TNF-alpha serum levels between patients with IS and control groups. MAP2K4 gene polymorphism rs3826392 C/A genotype carriers showed significantly higher IL-1b serum levels compared with AA genotype carriers (P = .029) in patients with IS. CONCLUSION: MAP2K4 gene polymorphism rs3826392 did not contribute to IS susceptibility, but rs3826392 C/A genotype carriers showed significantly higher IL-1b serum levels. This result suggests that rs3826392 may play a potential role in the IS inflammatory process. PMID- 26856462 TI - Good Clinical and Radiological Correlation from Standard Perfusion Computed Tomography Accurately Identifies Salvageable Tissue in Ischemic Stroke. AB - INTRODUCTION: It has been debated whether the penumbral pattern, as identified using multimodal imaging, is a specific marker of tissue viability in ischemic stroke. We assessed whether perfusion computed tomography (PCT) accurately identifies salvageable tissue and helps predict postreperfusion outcomes. METHODS: A retrospective study of patients with anterior circulation stroke undergoing reperfusion therapies who had a PCT before treatment and an assessment of vessel recanalization post treatment was conducted. Tissue at risk was considered as that with reduced cerebral blood flow, whereas the infarct core was the region of reduced cerebral blood volume, the mismatch region being salvageable tissue. The volume of hypodensity in slices corresponding to perfusion acquisition cage in 24-hour computed tomography (partial lesion volume [PLV]) was measured. Outcome variables were the amount of preserved tissue, that is, the difference between volumes of tissue at risk and PLV expressed as a percentage, and the modified Rankin Scale (mRS) score at 3 months. RESULTS: Patients (n = 34) meeting the inclusion criteria were included. Vessel recanalization was associated with a larger amount of tissue at risk preserved from definite lesion (89% [interquartile range {IQR}: 76-94] versus 46% [IQR: 23 86], P < .005). The amount of preserved tissue correlated with clinical outcome at 24 hours: for each 10% of preserved tissue, the National Institutes of Health Stroke Scale score improved by 3 points (95% confidence interval [CI]: -4.9 to .8, P = .007) and was the only predictor of independency (mRS score 0-2) following adjustment for covariates (odds ratio 1.15, 95% CI: 1.04-1.28, P = .005). CONCLUSIONS: PCT provides accurate markers of viability of tissue in acute ischemic stroke and could help predict the degree of improvement following reperfusion. PMID- 26856464 TI - A Four-Year Experience of Symptomatic Intracranial Hemorrhage Following Intravenous Tissue Plasminogen Activator at a Comprehensive Stroke Center. AB - BACKGROUND: To describe the 4-year experience of symptomatic intracranial hemorrhage (sICH) rate at a high-volume comprehensive stroke center. METHODS: All admitted adult (>=18 years) patients presenting with an ischemic stroke from 2010 to 2013 were included in this study. The primary outcome was sICH, defined as any hemorrhage with neurological deterioration (change in National Institutes of Health Stroke Scale score >=4) within 36 hours of intravenous tissue plasminogen activator (IV-tPA) treatment, or any hemorrhage resulting in death. Secondary outcomes were in-hospital mortality and having a favorable modified Rankin Scale (mRS) score (<=2). RESULTS: A total of 1925 did not receive intravascular (IV) or intra-arterial (IA) therapy; only 451 received IV therapy; and 175 received both IV and IA therapies. In IV-only patients, the overall rate of sICH was 2.2%; in IV and IA patients, the rate was 5.7%; and in patients who received no therapy, the rate was .4%. The IV-only group had an sICH rate of .9% in 2013. There were no differences in the adjusted odds of dying in the hospital between the study groups. IV-only treatment offered significantly better odds of achieving a favorable functional outcome, compared to no therapy, among patients with moderate stroke severity, whereas IV and IA treatments offered significantly better odds among patients with severe strokes. The odds of achieving a favorable functional outcome by discharge were decreased by 97% if patients suffered an sICH (OR = .03, 95%CI = .004, .19). CONCLUSIONS: Despite an increased risk of sICH with IV-tPA, treatment with IV-tPA continues to be associated with increased odds of a favorable discharge mRS. PMID- 26856465 TI - Toward improving the World Health Organization fifth moment for hand hygiene in the prevention of cross-infection. AB - BACKGROUND: The World Health Organization describes that there are 5 moments during a health care encounter when hand hygiene should be performed. This research explores a number of explanatory hypotheses to inform future intervention development with regard to improving compliance with the fifth moment. METHODS: A sequential, mixed-methods study was conducted using nonparticipant observation and a survey with focus groups informing the development of the questionnaire. A total of 484 participants were observed and 410 returned a postobservation questionnaire; a response rate of 85%. Analysis explored the role of organizational culture, professional culture/practice, and individual-level variables in explaining compliance with the fifth moment. RESULTS: Ninety-three percent of participants performed hand hygiene following the fifth moment. Compliance varied between regions, but not by professional group. More than 65% indicated that the fifth moment was clearly defined, achievable, valuable, encouraged, and widely known. However, 60% suggested that it was repetitive. There was a positive relationship between the performance of hand hygiene following the fifth moment and the perception that it was widely known. CONCLUSIONS: Interventions to improve compliance with the fifth moment should focus on promoting awareness of the fifth moment and how it should be implemented in practice. Mechanisms for raising awareness should include education and role modeling. PMID- 26856466 TI - Be seen and heard being clean: A novel patient-centered approach to hand hygiene. AB - A quasiexperimental pre- and posttest design was used to evaluate hand hygiene (HH) rates on a medical-surgical unit. Data were collected by asking patients if they had seen or heard staff members cleaning their hands. Sixty-five percent of patients reported seeing or hearing staff perform HH preintervention and 93% reported observations postintervention (P < .001). Through incorporating an auditory cue we engaged patients while removing the burden placed on them to question health care worker behavior, and increased both staff and patient awareness of personal HH behavior. PMID- 26856467 TI - Influence of pulsed-xenon ultraviolet light-based environmental disinfection on surgical site infections. AB - This study evaluates the influence of nightly pulsed-xenon ultraviolet light disinfection and dedicated housekeeping staff on surgical site infection (SSI) rates. SSIs in class I procedures were reduced by 46% (P = .0496), with a potential cost savings of $478,055. SSIs in class II procedures increased by 22.9%, but this was not significant (P = .6973). Based on these results, it appears that the intervention reduces SSI rates in clean (class I), but not clean contaminated (class II) procedures. PMID- 26856468 TI - Electronic surveillance for catheter-associated urinary tract infections at a university-affiliated children's hospital. AB - We sought to describe the characteristics of catheter-associated urinary tract infections (CAUTIs) in a children's hospital while demonstrating efficacy of electronic identification of CAUTIs. There were 25 CAUTIs identified over 24 months, with most (88%) occurring in the intensive care units (ICUs). The incidence of ICU CAUTIs decreased during the study period (P = .04). Concordance between electronic identification and validation by infection control staff was 83% and increased to 100% with correction of nursing documentation. PMID- 26856469 TI - Crib Mattress Investigation: A quality improvement study to assess mattress cover permeability and bacterial growth in crib mattresses. AB - PURPOSE: Any opening in a medical bed mattress cover may allow bodily fluids to enter the mattress, leading to contamination and potential nosocomial infection. This study's purpose was to assess permeability of crib mattress covers and measure bacterial growth within and on crib mattress surfaces. METHOD: Mattresses were selected randomly from hospital inventory. Bonney's blue dye was applied over mattress covers to assess permeability. Mattress cover surface swabs were acquired from standardized locations. Samples of mattress foam were acquired under sterile conditions. All samples were collected with the Eswab and eMRSA systems (Copan Diagnostics Inc, Brescia, Italy). Total aerobic bacteria count and colony types were assessed. Results are presented as mean +/- standard error of the mean, independent t tests and analysis of variance were used to analyze data, and significance was achieved with P < .05. RESULTS: All mattresses (n = 7) had Bonney's blue dye visible on underlying mattress foam. There were 77 samples and 44 had bacterial growth. Total bacterial count ranged from 0.2-11.6 CFU/cm(2) with mean of 1.7 +/- 0.38 CFU/cm(2). There was no relative differences between mattress sample location and colony type. All samples were negative for Staphylococcus aureus, including methicillin-resistant S aureus. CONCLUSIONS: Any crack in a mattress cover renders it permeable to fluid entering the mattress. Bacterial growth was present on mattress covers and within mattress foam. Mattresses support microbial viability from which nosocomial infection may occur. PMID- 26856470 TI - Type A aortic dissection with arch entry tear: Surgical experience in 104 patients over a 12-year period. AB - OBJECTIVE: To evaluate the efficacy of the frozen elephant trunk (FET) and total arch replacement (TAR) technique (FET + TAR) in the management of type A aortic dissection (TAAD) with arch entry tear. METHODS: Clinical outcomes were analyzed for 104 TAAD patients with arch entry tear undergoing FET + TAR at 4.7 +/- 3.5 days from symptom onset and compared with 728 TAAD patients with entry tears in elsewhere. The mean patient age was 49.3 +/- 9.3 years, compared with 45.6 +/- 10.8 years in other TAAD patients (P < .001). There were 84 men (80.8%). Hypertension was seen in 84.6% (88/104). RESULTS: Operative mortality was 8.6% (9/104). Spinal cord injury occurred in 3 cases (2.9%), stroke in 2 (1.9%), renal failure in 4 (3.8%) and limb ischemia in 2 (1.9%). Follow-up was 100% (95/95) at mean 5.6 +/- 2.6 years (range 1.3-11.6). Late death occurred in 2 cases (1.9%). Survival and freedom from late adverse events were 89.2% (95% confidence interval [CI], 81.3%-93.9%) and 85.0% (95% CI, 76.3%-90.8%) at 8 years, respectively. Both the stented and unstented distal aortic segments showed significant trends of false lumen shrinkage and true lumen expansion over time (P < .001). Of the 65 CT scans at mean 4.6 +/- 2.9 years postoperatively, the false lumen was completely obliterated in 63. Risk factors for arch entry tear were hypertension (odds ratio [OR], 2.091; 95% CI, 1.186-3.687; P = .011) and age (OR, 1.025; 95% CI, 1.002 1.048; P = .032). CONCLUSIONS: TAAD with arch entry tear was treated safely and durably by FET + TAR. Although patients with arch entry tear were somewhat older than other patients, operative mortality was not substantially higher despite their older age and arch location of entry tear. These results argue favorably for the use of the FET + TAR technique in the management of TAAD patients with arch entry tears. PMID- 26856471 TI - Adventitial inversion technique for type A aortic dissection distal anastomosis. AB - OBJECTIVE: Anastomosis in dissected aorta management remains challenging. The patent false lumen of remnant aorta influences the growth of the residual aorta after hemiarch replacement. We evaluated the beneficial effect of adventitial inversion technique for distal anastomotic reinforcement of hemiarch replacement in acute type A aortic dissection. METHODS: From 2006 to 2014, 90 patients with DeBakey type I aortic dissection who underwent hemiarch replacement for acute type A aortic dissection management at the National Cerebral and Cardiovascular Center were retrospectively analyzed. Patients were divided according to the technique used: the adventitial inversion technique in group A and the original Sandwich method with Teflon felt in group S. Surgical variables and aortic morphology from distal aortic anastomosis were evaluated by computed tomography after surgery. RESULTS: The mean follow-up time was 2.2 +/- 2.1 years with a follow-up rate of 91.1%. Cardiopulmonary bypass time was 208.2 +/- 93.9 minutes in group A and 220.6 +/- 93.9 minutes in group S; lower body circulatory arrest time was 51.6 +/- 10.2 minutes in group A and 54.5 +/- 17.8 minutes in group S. No significant differences were observed between groups. The overall hospital mortality rate was 10.0%. Postoperative false lumen thrombosis rate at proximal descending aorta on enhanced delayed phase computed tomography was significantly higher in group A than in group S. CONCLUSIONS: The adventitial inversion technique may facilitate thrombotic closure of the distal false lumen in acute type A aortic dissection management by hemiarch replacement. PMID- 26856472 TI - Cardiac magnetic resonance imaging characterizes stenosis, perfusion, and fibrosis preoperatively and postoperatively in children with anomalous coronary arteries. AB - OBJECTIVES: Using cardiac magnetic resonance imaging (MRI) with virtual angioscopy, we sought to evaluate coronary anatomy, myocardial injury, and left ventricular function in children with interarterial anomalous aortic origin of coronary artery before and after surgery. METHODS: We prospectively enrolled children 5 to 19 years old with interarterial anomalous coronary artery. Cardiac MRI was performed with respiratory-navigated steady-state free-precession 3 dimensional data set acquisition. Virtual angioscopy was used to evaluate the coronary ostia directly. Surgery consisted of the modified unroofing procedure. RESULTS: We enrolled 9 subjects between February 2009 and May 2015. Subjects were male, with an average age at surgery of 14.1 years. Anomalous coronary was right in 7 patients (77%) and left in 2. In all subjects, the proximal anomalous coronary arose tangential to the aorta with an elliptical, slitlike ostium. Before the operation, the proximal coronary artery was significantly smaller proximally than distally (2 vs 3.1 mm; P < .0001. After the operation, neo orifices were round and patent in 7 subjects; however, 2 subjects still had narrowed neo-orifices. New postoperative MRI findings included flattened septal wall motion (N = 1), small region of midmyocardial partial-thickness scar (N = 1), and dyskinetic septal wall motion with mild aortic insufficiency (N = 1). Left ventricular function was normal both before and after surgery (P = .85). CONCLUSIONS: Cardiac MRI with virtual angioscopy is an important tool for evaluating anomalous coronary anatomy, myocardial function, and ischemia and should be considered for initial and postoperative assessment of children with anomalous coronary arteries. PMID- 26856473 TI - Discussion. PMID- 26856474 TI - Emergency transcervical innominate artery clamping: Is it a real option? PMID- 26856475 TI - Perventricular repair of ventricular septal defects: Specific techniques have specific risks. PMID- 26856476 TI - It's not what you put in that is important, it's what you take out. PMID- 26856477 TI - Aortic ring autograft for reconstruction of the neo-pulmonary root in the arterial switch operation. PMID- 26856478 TI - Decellularization of Human Nasal Septal Cartilage for the Novel Filler Material of Vocal Fold Augmentation. AB - OBJECTIVES: The clinical application of allogenic and/or xenogenic cartilage for vocal fold augmentation requires to remove the antigenic cellular component. The objective of this study was to assess the effect of cartilage decellularization and determine the change in immunogenicity after detergent treatment in human nasal septal cartilage flakes made by the freezing and grinding method. METHODS: Human nasal septal cartilages were obtained from surgical cases. The harvested cartilages were treated by the freezing and grinding technique. The obtained cartilage flakes were treated with 1% Triton X-100 or 2% sodium dodecyl sulfate (SDS) for decellularization of the cartilage flakes. Hematoxylin and eosin stain (H&E stain), surface electric microscopy, immunohistochemical stain for major histocompatibility complex I and II, and ELISA for DNA contents were performed to assess the effect of cartilage decellularization after detergent treatment. RESULTS: A total of 10 nasal septal cartilages were obtained from surgical cases. After detergent treatment, the average size of the cartilage flakes was significantly decreased. With H&E staining, the cell nuclei of decellularized cartilage flakes were not observed. The expression of major histocompatibility complex (MHC)-I and II antigens was not identified in the decellularized cartilage flakes after treatment with detergent. DNA content was removed almost entirely from the decellularized cartilage flakes. CONCLUSION: Treatment with 2% SDS or 1% Triton X-100 for 1 hour appears to be a promising method for decellularization of human nasal septal cartilage for vocal fold augmentation. PMID- 26856479 TI - Comparison of the Wii Balance Board and the BESS tool measuring postural stability in collegiate athletes. AB - Concussions are a major health concern for athletes given the potential for these injuries in a wide range of sport activities. The leading concern for clinicians is that athletes are at risk for devastating consequences if they are not evaluated properly and cleared too early to return to play or competition. The evaluation of postural stability has been identified as an important aspect to the comprehensive management of such injuries. Clinicians are in need of a portable tool they can use in various settings to aid in decision making and health care delivery for concussed athletes. The Nintendo Wii Balance Board (Nintendo of America Inc., Redmond, Washington) is a portable, cost-effective tool that has the potential to aid in the evaluation of postural stability in concussed individuals. The purpose of this study was to evaluate the Wii Balance Board as an objective, user-friendly, cost effective, valid alternative tool for the measurement of postural stability in college athletes. This study questioned whether the Wii Balance Board, when compared to the Balance Error Scoring System (BESS), is an objective tool that can be used as an acceptable measurement of postural stability in college athletes. PMID- 26856480 TI - Effects of multimedia nursing education on disease-related depression and anxiety in patients staying in a coronary intensive care unit. AB - AIM: We evaluated the effectiveness of an accessibility-enhanced multimedia informational educational program in reducing depression and anxiety increasing satisfaction with the information and materials received by patients in coronary care unit. METHODS: We selected 100 patients from among the patients who stayed at or who underwent surgery at one of two ICUs for any reason who satisfied the eligibility criteria, and agreed to participate in the research. The participants were included in the control or experimental group by random selection. The patients completed the Hospital Anxiety Depression Scale during ICU admission and 1week after hospital discharge. RESULTS: The difference in HADSA score was significantly greater in patients who received education than in patients who did not receive multimedia nursing education (4.2+/-0.58 vs. 0.6+/-0.42; p<.01). Additionally, the difference in HADSD score was significantly greater in patients who received multimedia nursing education (2.2+/-0.53 vs. 0.64+/-0.46; p<.01). CONCLUSION: This study showed that anxiety and depression associated with hospital can be reduced with multimedia nursing education. PMID- 26856481 TI - Perceived cognitive changes with chemotherapy for breast cancer: A pilot study. AB - PURPOSE: The purpose of this study was to determine perceived cognitive functioning, fatigue, depression and general well-being among women before and after the initiation of chemotherapy for breast cancer compared to a sample of healthy women. METHOD: This descriptive, repeated measures study compared women receiving chemotherapy and healthy women. Women completed measures of quality of life, fatigue, cognitive changes and depression. RESULTS: Before chemotherapy, women with cancer reported more fatigue and depression than healthy women. After chemotherapy, women with cancer reported decreased cognitive functioning accompanied by more fatigue and depressive symptoms than healthy women. CONCLUSION: This study is one of the first to use multiple symptom measures before and after starting chemotherapy. Understanding cognitive changes and related symptoms that occur before and during chemotherapy for breast cancer is the first step toward helping women cope with changes that occur with breast cancer treatment. PMID- 26856482 TI - Applicability of the Nursing Outcomes Classification (NOC) to the evaluation of cancer patients with acute or chronic pain in palliative care. AB - OBJECTIVE: The aim of this study was to verify the clinical applicability of the Nursing Outcomes Classification (NOC) to the evaluation of cancer patients with a nursing diagnosis of acute or chronic pain in a palliative care unit. METHOD: A prospective longitudinal study performed on a sample of 13 adult cancer patients in a palliative care unit. Patients were followed for at least 4 days. Data were collected with an instrument containing eight nursing outcomes and nineteen NOC indicators. Statistical analysis was performed using generalized estimating equation models. RESULTS: The following outcome and indicator scores changed significantly over the course of the study: reported pain and length of pain episodes in the pain level outcome; social relationships in the personal well being outcome; respirator rate in the vital signs outcome; and describes causal factors in the pain control outcome. CONCLUSION: The NOC outcomes and indicators included in this study were able to successfully evaluate the clinical evolution of cancer patients in palliative care. These scores proved to be applicable for use in palliative nursing care. PMID- 26856483 TI - The effect of education given to primigravida women on fear of childbirth. AB - OBJECTIVE: The present study was conducted to determine the effect of education that is given information about the delivery room, labor and coping strategies with the fear of pain of childbirth in primigravida women. DESIGN: This study was conducted experimentally using pre-post tests and a control group. PARTICIPANTS AND SETTING: A total of 99 primigravida women with 50 in the study group and 49 in the control group at a maternity hospital in a city of middle region of Turkey were recruited to the study. METHODS: Data were collected using the Pregnant Introduction Form, Interview Form After Delivery and Wijma Delivery Expectancy/Experience Questionnaire (W-DEQ), version A. Verbal informed consent and approval were obtained from the participants and ethical committee. Preparatory labor education was provided in two sessions between pregnancy weeks 28 and 34 to the women in the study group. Fisher, MC Pearson, chi-square, Mann Whitney U and Wilcoxon t tests were used for statistical data analysis. RESULTS: In the first interview session, no significant difference was found between W-DEQ A scores of the study and control groups. The mean pre-education W-DEQ-A score was 61.1 while it was 42.0 post-education in the study group. The post-education W-DEQ-A score was 58.5 in the control group while it was 42.0 in the study group. CONCLUSIONS: It was determined that positive perception regarding birth was provided and fear of childbirth decreased with the preparation education for birth. PMID- 26856484 TI - Clinical decision-making among new graduate nurses attending residency programs in Saudi Arabia. AB - PURPOSE: This study examined the impact of residency programs on clinical decision-making of new Saudi graduate nurses who completed a residency program compared to new Saudi graduate nurses who did not participate in residency programs. DESIGN: This descriptive study employed a convenience sample (N=98) of new graduate nurses from three hospitals in Saudi Arabia. A self-administered questionnaire was used to collect data. Clinical decision-making skills were measured using the Clinical Decision Making in Nursing Scale. METHODS: Descriptive statistics, independent t-tests, and multiple linear regression analysis were utilized to examine the effect of residency programs on new graduate nurses' clinical decision-making skills. FINDINGS: On average, resident nurses had significantly higher levels of clinical decision-making skills than non-residents (t=23.25, p=0.000). Enrollment in a residency program explained 86.9% of the variance in total clinical decision making controlling for age and overall grade point average. CONCLUSIONS: The findings of this study support evidence in the nursing literature conducted primarily in the US and Europe that residency programs have a positive influence on new graduate nurses' clinical decision-making skills. CLINICAL RELEVANCE: This is the first study to examine the impact of residency programs on clinical decision-making among new Saudi graduate nurses who completed a residency program. The findings of this study underscore the need for the development and implementation of residency programs for all new nurses. PMID- 26856485 TI - Food security, maternal feeding practices and child weight-for-length. AB - BACKGROUND: Over consumption of energy-dense nutrient-poor foods may contribute to childhood obesity. We hypothesized that greater than recommended servings of sugar sweetened beverages and foods, indicators of food security, and a high maternal recumbent weight-for-length are positively associated with high percentages of child overweight/obesity. METHODS: This secondary data analysis consisted of a sample of 240 mother-child dyads. The original studies were designed to examine the effect of a public health nursing intervention on optimal childhood growth for low-income, minority children. Eligibility to participate included: 1) mothers self-identified as Hispanic; 2) children were 12-24 months old; and 3) children were enrolled in the Special Supplemental Nutrition Program for Women, Infants and Children (WIC); and 4) children were free of any major disease. Multivariate logistic regression examined the association between child weight, weight-for-length, maternal recumbent weight-for-length, child's eating schedule, maternal attitudes on feeding, food security, and consumption of sugar sweetened beverages, desserts and fatty meats. RESULTS: Receiving SNAP was positively associated with child weight-for-length (WL). Children whose mothers reported ever having received SNAP were 2.01 times more likely to be overweight compared to children whose mothers did not report ever having received SNAP (95% CI=1.04-3.90). Children who consumed desserts were 2.87 times more likely to be overweight compared to children who did not consume desserts (95% CI=1.19-6.88). Also, child's caloric intake was significantly associated with child WL. Children who consumed more calories were 1.00 times more likely to be overweight compared to children who consumed fewer calories (95% CI=1.00-1.00). DISCUSSION: Research on food security and children's weight has reported mixed findings. Methodological issues have been identified as contributory to the inconsistent findings. Of paramount importance to these studies is the measurement of low food security. CONCLUSION: Children in this sample who were food insecure, as indicated by SNAP recipients, were more likely to have a higher WL measurement. Future studies should focus on the correlation between food security and hunger/satiety cues. PMID- 26856486 TI - Efficacy of the theory of planned behavior in predicting breastfeeding: Meta analysis and structural equation modeling. AB - PURPOSE: This study assessed the applicability and efficacy of the theory of planned behavior (TPB) in predicting breastfeeding. BACKGROUND: The TPB assumes a rational approach for engaging in various behaviors, and has been used extensively for explaining health behavior. However, most studies have tested the effectiveness of TPB constructs in predicting how people perform actions for their own benefit rather than performing behaviors that are beneficial to others, such as breastfeeding infants. A meta-analysis approach could help clarify the breastfeeding practice to promote breastfeeding. METHODS: This study used meta analytic procedures. We searched for studies to include in our analysis, examining those published between January 1, 1990 and December 31, 2013 in PubMed, Medline, CINAHL, ProQuest, and Mosby's Index. We also reviewed journals with a history of publishing breastfeeding studies and searched reference lists for potential articles to include. RESULTS: Ten studies comprising a total of 2694 participants were selected for analysis. These studies yielded 10 effect sizes from the TPB, which ranged from 0.20 to 0.59. Structural equation model analysis using the pooled correlation matrix enabled us to determine the relative coefficients among TPB constructs. Attitude, subjective norms, and perceived behavioral control were all significant predictors of breastfeeding intention, whereas intention was a strong predictor of breastfeeding behavior. Perceived behavioral control reached a borderline level of significance to breastfeeding behavior. Theoretical and empirical implications are discussed from the perspective of evidence-based practice. PMID- 26856487 TI - Hypertension and related lifestyle factors among persons living in rural Nicaragua. AB - BACKGROUND: Globally about 40% of adults are diagnosed with hypertension, with high-income countries having a lower prevalence than low-income countries. However, there are limited data about adult hypertension prevalence in Nicaragua. The purpose of this study was to determine the prevalence of hypertension in rural coffee farm workers. METHODS: A convenience sample of 229 adult coffee farm workers was used. Blood pressure was measured using an established protocol and the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC-7) guidelines. RESULTS: Nearly 60% of the sample reported at least one prior blood pressure measurement. Hypertension was detected in 16.7% of males and 26.3% of females (20.7% of the total). Prehypertension was detected in 59.3% of males and 27.7% of females (46.2% of the total). Of the men, 51.4% reported smoking at least some days and just over one third of the sample reported adding extra salt to their food. DISCUSSION: While the prevalence of hypertension in this sample is lower than global estimates, almost half of the sample had prehypertension, demonstrating an area where health promotion efforts could be focused. Given the limited funding and resources often available in these areas, increasing disease prevention efforts (including health promotion and wellness programs) and establishing settings that provide outreach and education, may improve chronic disease management and prevent comorbidities from occurring. PMID- 26856488 TI - Development of an instrument to measure deliberate practice in professional nurses. AB - PURPOSE: This paper describes the development of the Deliberate Practice in Nursing Questionnaire (DPNQ) and the reliability and validity characteristics of the instrument. METHODS: A cross-sectional, descriptive study assessed the DPNQ in a sample of critical care registered nurses (RN). It was conducted at one large Midwestern teaching hospital. A medical intensive care unit (ICU), a surgical ICU, and a trauma/burn ICU participated. Instrument construction involved item development based on a literature review, an existing deliberate practice questionnaire and existing parameters of deliberate practice in nursing. Content reliability and validity were established by expert panel review and survey testing. Probit analysis of survey data was used to develop a composite score for the DPNQ. RESULTS: Expert panel review revealed an inter-rater agreement (80% reliability) of .92-.96 and a content validity index of 0.94. The final DPNQ consists of 24 items with six subcategories and a composite score of 96. Cronbach's alpha coefficient for the DPNQ in this study was .660 (standardized, .703). The instrument was further validated with the Nurse Competence Scale. Deliberate practice was significantly, positively correlated with competence (rs=.366, p=001). CONCLUSIONS: Findings from the expert panel provided guidance for development and revision of the DPNQ. Survey testing of the instrument revealed a promising measure of deliberate practice with good reliability and validity characteristics. Identification of a relationship between deliberate practice and competence confirms existing evidence in other domains, providing further validation. Understanding deliberate practice provides a unique way to examine nursing expertise. PMID- 26856489 TI - Falls prevention: Identification of predictive fall risk factors. AB - Patient falls are the most common adverse safety event in hospitals and healthcare facilities nationwide. There are many risk factors associated with inpatient falls such as medications, unsteady gait, alteration in mental status, and environmental hazards. Risk assessment is the primary intervention for falls prevention. This study aims to provide a detailed review of the literature to identify and synthesize research evidence on risk factors that may contribute to patient falls in the adult inpatient hospital setting that are not captured by current fall risk assessment tools. After the identification of those key risk factors not found on the most common fall risk assessment tools, the results of this review will be used to develop a new evidence based fall risk assessment tool. PMID- 26856490 TI - Evolution of childbirth expectations in Spanish pregnant women. AB - PURPOSE: To analyze the change of childbirth expectations over the course of pregnancy as well as their relation to socio-demographic and clinical variables. BACKGROUND: The study of expectations in pregnant women is gaining more interest from a biopsychosocial approach because of its consequences on pregnant women's wellbeing. To our knowledge there are no previous studies analyzing the evolution of childbirth expectations over the course of pregnancy. METHODS: Longitudinal study (first trimester and third trimester). Women were evaluated for childbirth expectations in their first trimester (n=285) and third trimester (n=122) of pregnancy. They also completed questionnaires collecting socio-demographic information. RESULTS: Childbirth expectations appear to remain more or less stable over the course of pregnancy, although they tend to become slightly negative at the end of gestation, specifically referring to personal control and delivery circumstances. Multiparity and planned pregnancy are associated with higher positive expectations. CONCLUSION: It seems essential to explore and to try to adjust childbirth expectations to more realistic ones, in order for them to be fulfilled. Midwives and other maternity healthcare providers play a key role in this regard. PMID- 26856492 TI - A structural model of health behavior modification among patients with cardiovascular disease. AB - PURPOSE: The purpose of the study was to test a structural equation model in which social support, health beliefs, and stage of change predict the health behaviors of patients with cardiovascular disease. METHOD: A cross-sectional correlational design was used. Using convenience sampling, a survey about social support, health belief, stage of change, and health behavior was completed by 314 adults with cardiovascular disease from outpatient clinics in 2 university hospitals in Korea. Data were analyzed using a structural equation model with the Analysis of Moment program. RESULTS: The participants were aged 53.44+/-13.19 years (mean+/-SD), and about 64% of them were male. The proposed model fit the data from the study well, explaining 19% and 60% of the variances in the stage of change and health behavior, respectively. CONCLUSION: The findings indicate that the performance of health behavior modification among the patients with cardiovascular disease can be explained by social support, health belief, and stage of change based on a health-belief and stage-of-change model. Further studies are warranted to confirm the efficacy of health-promoting strategies in initiating and maintaining the performance of health behaviors by providing social support from family and medical staff and enhancing health belief. PMID- 26856491 TI - Methodological challenges collecting parent phone-call healthcare utilization data. AB - Recommendations by the National Institute of Nursing Research and other groups have strongly encouraged nurses to pay greater attention to cost-effectiveness analysis when conducting research. Given the increasing prominence of translational science and comparative effective research, cost-effective analysis has become a basic tool in determining intervention value in research. Tracking phone-call communication (number of calls and context) with cross-checks between parents and healthcare providers is an example of this type of healthcare utilization data collection. This article identifies some methodological challenges that have emerged in the process of collecting this type of data in a randomized controlled trial: Parent education Through Simulation-Diabetes (PETS D). We also describe ways in which those challenges have been addressed with comparison data results, and make recommendations for future research. PMID- 26856493 TI - Multiple symptoms, functioning, and general health perception in people with severe COPD over time. AB - BACKGROUND: Little is known of the effect over time of multiple symptoms on functioning and general health perception in people with severe chronic obstructive pulmonary disease (COPD). This study examined the relationship between changes in multiple symptoms, functioning, and general health perception over a 3-year period. METHODS: The longitudinal study used a dataset from the National Emphysema Treatment Trial. Variables were assessed at baseline, 6, 12, 24, and 36 months in 152 people with COPD. Individual regression analysis was used to analyze the data. RESULTS: The number and frequency of symptoms increased; physical and social functioning and general health perception decreased over 3 years. Changes in dyspnea were more significantly associated with a decline in physical functioning and general health perception than changes in multiple symptoms. CONCLUSION: Efforts should be made to relieve multiple symptoms and dyspnea over time to slow the decline in functioning and general health perception in people with COPD. PMID- 26856494 TI - Psychometric evaluation of the Diabetes Self-Management Instrument Short Form (DSMI-20). AB - PURPOSE: Accurately assessing the self-management of patients with diabetes requires a valid and reliable assessment instrument. The purpose of this study was to revise and simplify the original assessment instrument (DSMI-35), and to evaluate the psychometric properties of the new short form (DSMI-20) in order to enhance its practicality in clinical settings. METHODS: The short form instrument (DSMI-20) was created by revising our previous longer instrument (DSMI-35) through having in-depth small group discussions and validation by experts. The draft (DSMI-20) was pilot tested, and its items were analyzed. We verified the draft (DSMI-20) by conducting an exploratory factor analysis (EFA) and correlating the (DSMI-20) with the diabetes empowerment scale (DES). We tested its reliability including internal consistency and established its test-retest reliability using Cronbach's alpha and Pearson correlation coefficients. RESULTS: EFA identified four factors with loadings ranging from -0.727 to -0.535 and 0.547 to 0.907: communication with HCPs, self-integration, self-monitoring of blood glucose, and problem solving. These factors accounted for 57.110% of the total variance. The Cronbach's alpha coefficient of the DSMI-20 total scale was 0.925 and of subscales ranged from 0.838 to 0.892. The test-retest correlation for the DSMI-20 total scale was acceptable (r=0.790, p<0.001). Correlation with the DES was r=0.552 (p<0.001). CONCLUSION: The DSMI-20 is a rapid, viable assessment tool for identifying self-management problems among patients with diabetes. PMID- 26856496 TI - Migration background and overall satisfaction with pre-hospital emergency care. AB - OBJECTIVES: This study was designed to explore how sociodemographic factors of the patient/patient's relatives including migrant status and service-related aspects influence overall satisfaction with pre-hospital emergency care. METHODS: A descriptive-analytical study was conducted on 218 persons (57 migrants and 161 nonmigrants) who had received pre-hospital emergency care directly (as a patient) or indirectly (as a significant other) in Germany. Sociodemographic data and service-related aspects were entered into a hierarchical regression analysis in order to identify their influence on overall satisfaction. RESULTS: Altogether, 58.3% of the variance of the overall satisfaction with pre-hospital emergency care can be explained by the final model. Of this sum, only 9.8% is explained by sociodemographic factors and 47.3% by service-related aspects. Migrant status per se did not show any significant influence, whereas no or a basic level of German language skills is significantly negatively associated with overall satisfaction. Professional and emotional/social competencies of the emergency personnel are significantly positively associated with overall satisfaction with pre-hospital emergency care. CONCLUSIONS: Sociodemographic-related factors, excepted from language skills, seem to be largely unrelated to overall satisfaction with pre hospital emergency care. Service-related factors such as the emergency personnel's professional and social/emotional competencies appear as the main factors determining overall satisfaction with pre-hospital emergency care. PMID- 26856495 TI - Economic evaluation of registered nurse tenure on nursing home resident outcomes. AB - PURPOSE: Little is known about the economic implications of nursing home (NH) registered nurse (RN) tenure on resident outcomes. This study evaluated the cost effectiveness of two nurse workforce scenarios focusing on RN tenure (high versus low), and the associated transfers from NH to the hospital. METHODS: A decision tree was constructed to compare the incremental costs and effects of RN tenure scenarios on NH resident transfers to the hospital under two NH staffing scenarios: high versus low levels of RN tenure. Three outcomes were modeled: 1) dollars per hospitalization avoided, 2) dollars per hospitalization and death avoided, and 3) dollars per death avoided. RESULTS: The total costs of care for the low tenure scenario were $34,108 per month compared to the high tenure scenario at $29,442 per month. Effectiveness of the high tenure was greater across all 3 outcomes (incremental effectiveness ranged from 0.925 to 0.974 depending on outcome), indicating that high tenure was the dominant strategy (that is less costly and more effective). CONCLUSIONS: Higher RN tenure was a dominant strategy across the 3 outcomes. This was a fairly robust finding despite the variations in the model and uncertainty in the input parameters. Aligning quality outcomes with cost effectiveness is imperative to driving the direction of health policy in the United States. Better prevention of hospitalizations by having an experienced RN workforce will not only improve resident quality of care but will allow NHs to realize the value of retaining a skilled workforce. PMID- 26856497 TI - Consent and enrollment process: achieving high enrollment rates for obstetric research. AB - AIM: The aim was to study the development, design, and implementation of a patient consent and enrollment initiative to identify strategies that enhanced participation. BACKGROUND: Consent and enrollment of patients, especially pregnant women, remains a challenge in healthcare research. Although many barriers have been identified, strategies to consistently improve consent and enrollment are less defined. METHODS: A case study was conducted on a consent and enrollment approach aimed at optimizing participation of mothers who delivered their infants from July 1, 2010 through June 30, 2013. Data were gathered through practitioner interviews, focus groups, and documentation review for each year of the study. RESULTS: A total of 19,236 mothers enrolled, representing an 85% enrollment rate at the five study sites. Enrollment rates improved over time with increased nursing engagement in patient recruitment, site specific adaptations and patient education strategies. CONCLUSIONS: Nursing's active role in implementation and rapid feedback loop of a multifaceted consent and enrollment program showed promise. PMID- 26856499 TI - Connecting East and West by a developmental theory for older adults: Application of Baltes' Selection, Optimization, and Compensation model. AB - Age-related changes in cognitive and physical function can affect safe driving performance. As the population of older adults increases in the United States there will be a simultaneous rise in the number of older adult drivers. Tai Chi, a non-traditional form of exercise with both physical and cognitive benefits may enhance driving performance. A lifespan developmental theory (Baltes' Selective Optimization with Compensation model) is used to study the relationship between Tai Chi exercise and driving performance in older adults. Application of this theory was pivotal in building a bridge between a non-traditional practice and Western-based research to study an intervention that can be used to promote and sustain well-being in older adults. PMID- 26856498 TI - Reduction in the incidence of pressure ulcers upon implementation of a reminder system for health-care providers. AB - PURPOSE: To measure the clinical impact of the introduction of a reminder system for healthcare professionals to alert patients who are at risk for pressure ulcers (PU). METHODS: This was a pre- and post-test study of patients who were discharged from 6 medical-surgical units of the University Hospital of Fuenlabrada in 2009 and 2010. Beginning in January 2010, implementation of an on screen list of reminders was automatically updated daily on the units' computers including patient arrival date, last assessment of ulceration risk and location of any PU. The cumulative incidence of PU was measured for patients discharged in 2009 (group A: healthcare professionals were not exposed to on-screen reminder) and 2010 (group B: healthcare professionals were exposed to on-screen reminder list). The relative risk (RR) was estimated. The study was completed with a stratified analysis and binary logistic regression. RESULTS: In group A, there were 84 cases of PU among 9263 patients discharged (0.9%); whereas in group B, there were 59 cases among 9220 patients discharged (0.6%). The RR of PU for group B/group A was 0.706 (p=0.038). In the logistic regression analysis, after adjusting for study variables, the odds ratio of PU B/A was 0.558. CONCLUSION: A list of on-screen reminders at the beginning of a healthcare professional's shift to inform them of patients at risk for developing a PU was effective at reducing the incidence of these clinical burdens. PMID- 26856500 TI - Telephone nurses' communication and response to callers' concern--a mixed methods study. AB - AIMS: The aim of this study was to describe telephone nurses' and callers' communication, investigate relationships within the dyad and explore telephone nurses' direct response to callers' expressions of concern BACKGROUND: Telephone nurses assessing callers' need of care is a rapidly growing service. Callers with expectations regarding level of care are challenging. METHOD: RIAS and content analysis was performed on a criterion sampling of calls (N=25) made by callers who received a recommendation from telephone nurses of a lower level of care than expected. RESULTS: Telephone nurses mainly ask close-ended questions, while open ended questions are sparsely used. Relationships between callers' expressions of Concern and telephone nurses responding with Disapproval were found. Telephone nurses mainly responded to concern with close-ended medical questions while exploration of callers' reason for concern was sparse. CONCLUSION: Telephone nurses' reluctance to use open-ended questions and to follow up on callers' understanding might be a threat to concordance, and a potential threat to patient safety. PMID- 26856501 TI - Low literacy self-care management patient education for a multi-lingual heart failure population: Results of a pilot study. AB - PURPOSE: The purpose of this pilot study was to test the impact of language-free, low literacy self-care management patient education materials in an ethnically diverse multilingual heart failure (HF) population. METHODS: A one group pre-test post-test design measured changes in self-care, knowledge and health-related quality of life (HRQL) after a 1 month intervention using language-free, low literacy self-care management patient education materials and delivered by a health educator. RESULTS: The ethnically diverse sample (n=21) was predominately male (72%), 48% Black, 42% Hispanic, and 28% marginal/inadequate literacy. There were significant improvements in self-care and knowledge but not HRQL. CONCLUSIONS: Language-free, low literacy self-care patient education may facilitate improved self-care and knowledge in diverse populations who are at risk for poor HF outcomes. PMID- 26856502 TI - The Chinese family-centered care survey for adult intensive care unit: A psychometric study. AB - AIMS: This study aimed to develop a family-centered care survey for Chinese adult intensive care units and to establish the survey's psychometric properties. BACKGROUND: Family-centered care (FCC) is widely recognized as an ideal model of care. Few studies have explored FCC perceptions among family members of adult critical care patients in Asian countries, and no Chinese FCC measurement has been developed. METHODS: An English version of the 3-factor family-centered care survey for adult intensive care units (FCCS-AICU) was translated into Chinese using a modified back translation procedure. Based on the literature review, two additional concepts, information and empowerment, were added to the Chinese FCCS AICU. The psychometric properties of the Chinese FCCS-AICU were determined with 249 family members from a medical center in Taiwan and were tested for construct and convergent validity, and internal consistency. RESULTS: Both the monolingual and bilingual equivalence tests of the English and Chinese versions of the 3 factor FCCS-AICU were supported. Exploratory factor analysis supported the 5 factor structure of the Chinese FCCS-AICU with a total explained variance of 58.34%. The Chinese FCCS-AICU was correlated with the Chinese Critical Care Family Needs Inventory. Internal consistency, determined by Cronbach's alpha, for the overall scale was .94. CONCLUSIONS: The Chinese FCCS-AICU is a valid and reliable tool for measuring perceptions of FCC by family members of adult intensive care patients within Chinese-speaking communities. PMID- 26856503 TI - Predictors of routine episiotomy in primigravida women in Oman. AB - PURPOSE: Episiotomy is still the most common surgical procedure performed on women, despite the evidence against its routine use. This cross-sectional study was conducted to determine the practice and predictors of routine episiotomy on primigravidae in Oman. METHODS: Demographic data, reasons for and rate of performing routine episiotomies, and perceptions of 269 obstetricians, midwives and nurses from 11 hospitals in Oman regarding the procedure were recorded and analyzed. RESULTS: The rate of episiotomies was 66%. In terms of performing routine episiotomies (p<0.05): non-Omanis were 4.49 times more likely than Omanis; bachelor's degree-holders were 2.26 more likely than diploma-holders; and regional hospitals were 2.36 times more likely than tertiary hospitals. The majority perceived episiotomies "reduce spontaneous perineal tearing risk", "reduce shoulder dystocia complications", and allow for "easier suturing". CONCLUSION: The rate of episiotomies was higher than other similar contexts. An urgent intervention is necessary to curb this excessive practice, and create a culture of evidence-based practice to deal with misleading perceptions. PMID- 26856504 TI - Dyadic recruitment in complementary therapy studies: experience from a clinical trial of caregiver-delivered reflexology. AB - PURPOSE: As home-based care continues to be a growing trend in health care, involvement of friend and family caregivers in the management of illness becomes essential. However, before nurses can prepare caregivers to engage in various types of care, an evidence base needs to be established via randomized controlled trials (RCTs). Research suggests that recruiting cancer patients and their friend or family caregivers into RCTs presents challenges. The purpose of this paper is to illustrate the barriers to recruitment of patient-caregiver dyads into a RCT of caregiver-delivered reflexology and to recommend strategies to address such barriers. METHODS: This paper reports on a nurse-directed RCT that involved recruitment efforts unique to a caregiver-delivered reflexology protocol for advanced-stage breast cancer patients. Ineligibility due to caregiver-related reasons, consent among eligible patients (out of 551 approached patients), and reasons for refusal were analyzed. RESULTS: Almost one-third of patients were found to be ineligible due to the lack of a caregiver to participate with them and provide this form of social support. Among eligible patients, the consent rate for this dyadic study is much lower than that of previous RCTs of reflexologist-delivered reflexology that enrolled just patients, not dyads. CONCLUSION: Implications for nursing practice and research include addressing the need for greater social support for patients and strategies for problem-solving refusal reasons during study enrollment. PMID- 26856505 TI - Attitudes of patients towards being cared for by male nurses in a Jamaican hospital. AB - AIM: To determine the attitudes of patients towards male nurses in a Jamaican hospital. BACKGROUND: More males in nursing will help to address the nursing shortage and provide diversity in the profession. Patient attitudes towards male nurses will influence recruitment and retention. METHODS: A cross-sectional study was used. Data were collected using a self-administered questionnaire and an attitudinal measuring scale. RESULTS: Seventy-three patients responded (response rate 91%). Male nurses were perceived negatively by 51% of respondents. However, only 10% had a negative perception of the care they received from male nurses. More males (80%) than females (54%) had a negative attitude towards receiving an enema from a male nurse. CONCLUSIONS: Patients generally had a negative attitude towards male nurses but had a positive view if they were cared for by a male nurse. These traits can be used as the basis of changing the gender balance of nurses in Jamaica. PMID- 26856506 TI - The path to development of the Hozho Resilience Model for nursing research and practice. AB - This article describes how the Dine (Navajo) Hozho wellness philosophy, along with nursing research and theory, informed the development of a theoretical nursing model, the Hozho Resilience Model that can be used to generate patient centered nursing knowledge through connections among our theories, research, and practice. The Hozho Resilience Model is a model that can be used to understand American Indian worldviews in relation to health, and may also be used to guide future research and nursing practice with the American Indian population. PMID- 26856507 TI - Implementation and evaluation of the medication management in nursing units of a university hospital by means of a quality improvement cycle. AB - AIMS: The aim of this study was to improve compliance with protocols for the correct handling and storage of medication, both in medication rooms and on resuscitation trolleys in order to reduce the level of adverse effects on inpatients. BACKGROUND: The most frequent adverse effects in healthcare are due to medication errors. METHODS: Twenty hospital units were studied in 2012. Their medication rooms and resuscitation trolleys share the same medication supply system. Twelve criteria were evaluated and in the first assessment, corrective measures were implemented and criteria were evaluated again. RESULTS: In the first evaluation, the total amount of cases of noncompliance was 153 (65.38%). Seven corrective measures were implemented on the 6 criteria which accumulate 60% of the noncompliance cases. After that, 81 noncompliance cases (34.62%) were obtained. Almost all of evaluated criteria showed an improvement. Nine of the 12 criteria evaluated showed a statistically significant improvement in the second assessment. CONCLUSIONS: A quality improvement cycle is a useful tool to identify safety problems, related to management of medication rooms and resuscitation trolleys of nursing units. It is possible to identify and implement improvement measures without any additional cost. PMID- 26856508 TI - Characteristics of child health care practitioners in overweight prevention of children. AB - OBJECTIVES: To identify behavioral and personal characteristics of child health care (CHC) practitioners that influences the effect of early overweight prevention in children. METHODS: In total 216 questionnaires were filled out by CHC practitioners from four organizations in the Netherlands. RESULTS: There is a gap between awareness of the problem overweight in early childhood and actually discussing this with parents, as well as a gap between the existing recommendations and the perceived importance of early overweight prevention. Despite the fact that nurses have a more central task in life-style support than physicians, they reported to have less knowledge and skills than physicians. CONCLUSIONS: While both CHC physicians and nurses need support in improving their knowledge and skills, it is the nurses who need more support. A more structured and tailored implementation strategy with more emphasis on the needs of the nurses and physicians may improve early overweight management. PMID- 26856509 TI - Methodological factors conducting research with incarcerated persons with diabetes. AB - OBJECTIVE: The aim of this study was to describe methodological issues specific to conducting research with incarcerated vulnerable populations who have diabetes. BACKGROUND: Much has been written about the ethical and logistical challenges of conducting research with vulnerable incarcerated populations. However, conducting research with incarcerated persons with diabetes is associated with additional issues related to research design, measurement, sampling and recruitment, and data collection procedures. METHOD: A cross sectional study examining the relationships of diabetes knowledge, illness representation and self-care behaviors with glycemic control in 124 incarcerated persons was conducted and serves as the basis for describing methodological factors for the conduct of research with an incarcerated population with diabetes. RESULTS: Within this incarcerated population with diabetes, sampling bias due to gender inequity, recruitment of participants not using insulin, self reported vision impairment, and a lack of standardized instruments especially for measuring diabetes self-care were methodological challenges. Clinical factors that serve as potential barriers for study conduct were identified as risk for hypoglycemia due to insulin timing and other activities. CONCLUSION: Conducting research with incarcerated persons diagnosed with diabetes requires attention to a set of methodological concerns above and beyond that of the ethical and legal regulations for protecting the rights of this vulnerable population. To increase opportunities for conducting rigorous as well as facility- and patient-friendly research, researchers need to blend their knowledge of diabetes with an understanding of prison rules and routines. PMID- 26856510 TI - Mandatory early warning scoring--implementation evaluated with a mixed-methods approach. AB - AIM: The aim of this study was to evaluate adherence to an intervention optimizing in-hospital monitoring practice, by introducing early warning scoring (EWS) of vital parameters. BACKGROUND: Interventions comprising EWS systems reduce in-hospital mortality, but evaluation of adherence to such interventions is required to correctly interpret interventional outcome. METHOD: Adherence was evaluated with a mixed-methods approach. Quantitative data, obtained pre interventionally (2009) and postinterventionally (2010 and 2011), were used to calculate and compare time intervals between scorings of vital parameters. Semi structured interviews were used to evaluate the implementation process. RESULTS: We found significant reductions in time intervals between measurements of vital parameters in 2011 compared to 2009. Scorings of vital parameters were repeated within 8 hours in 71-77% of patients scoring total modified EWS levels of 0, 2 or 4. The theme Motivation by clinical relevance and meaningfulness was identified as crucial to the implementation process. CONCLUSION: High adherence to an intervention may be strongly related to nurses' perceived clinical relevance of the intervention. PMID- 26856511 TI - "Express testing" in STI clinics: extant literature and preliminary implementation data. AB - In an era of stagnant resources for sexually transmitted infection (STI) and HIV testing clinics, and at a time of ongoing-and in some cases increasing-STI and HIV transmission, it is important to trial and evaluate novel STI/HIV testing strategies. Based on the extant literature, one such approach is express testing, which includes full STI/HIV testing (as per clinical indication and client request), altered pretest counseling, and no physical examination for both men and women. In this paper, we overview the available research about express testing, including the literature on less-invasive testing, the effects of risk reduction counseling HIV testin/HIV testing, available research on various HIV testing modalities, and the reasons people undergo such testing. Thereafter, we overview our express testing program, which includes a detailed review of our clinical processes (which are unique within the published literature). Lastly, we provide some preliminary pre-implementation data to support the proposed efficacy of express testing. PMID- 26856512 TI - Assessing health literacy in safety net primary care practices. AB - Health literacy is now recognized as a crucial element of patient safety. Measuring health literacy in busy primary care practices can be challenging. This article presents findings from a study in which a relatively recent tool, the Newest Vital Sign (NVS) was used in seven safety net primary care practices, five of which were nurse managed health centers. The NVS is a promising tool that could be used extensively in most primary care practices. Providers and staff felt the use of the NVS would be beneficial in identifying low health literacy patients. This study supported previous research on low health literacy as well as the predictors of health literacy. The study also confirmed the NVS as a tool that is efficient to administer while maintaining work flow. PMID- 26856513 TI - Stress and coping of parents caring for a child with mitochondrial disease. AB - Mitochondrial disease comprises a group of rare, genetic, life-limiting, neurodegenerative disorders known to affect children. Little is known about disease-related challenges, parental stress, and coping when caring for a child with a mitochondrial disease. PURPOSE: This study explored disease-related characteristics and parental stressors and coping behaviors related to caring for a child with mitochondrial disease. METHODS: Internet surveys were posted on known mitochondrial disease websites for parent completion. Surveys included demographic items and two questionnaires: Coping Inventory for Parents (CHIP) and Pediatric Inventory for Parents (PIP). Descriptive data were collected and correlations used to determine relationships between parenting stress, coping, and demographic variables. RESULTS: The majority of participants (n=231) were mothers (95%) of children with mitochondrial disease around the age of 10 years (M=9.85). On average, children had 6 organs involved (M=6.02) and saw 7 different specialists (M=7.49); 61% were hospitalized in the past year. Significant correlations (p<0.05) were found between parenting stress and parent age, parent income, parent education, child age, child age at diagnosis, presence of developmental delays, number of hospitalizations, number of medical visits, number of organs involved, and number of specialists seen. Significant correlations were also found between parenting stress and coping behaviors such as family integration, social support and understanding health care. CONCLUSIONS: The ability to identify disease-related challenges, stressors, and coping strategies in parents of children with mitochondrial disease is novel and can assist nurses to provide disease-sensitive, family-focused care and improve child health outcomes. PMID- 26856514 TI - Diabetes nurse case management: Improving glucose control: 10 years of quality improvement follow-up data. AB - The purpose of this retrospective case-control review is to determine the effectiveness of a registered nurse case managers (RNCMs) certified diabetes educator (CDE) quality improvement case management program. RNCMs have a long tradition of providing chronic care intervention, particularly for the high-risk diabetes population with glycosylated hemoglobin (A1C) of 9% or more. However, limited data are available with regard to evaluation of such programs in a Veterans Health Administration population. RESULTS: A large population (N=3956) of high-risk veterans with a baseline A1C of 9% or more (mean=10.6%) was seen by the RNCM's. Paired T-tests of A1C after the last RNCM visit showed a statistically significant A1C reduction (p<0.001) (mean=8.5%), after 14-26 months of intervention. CONCLUSIONS: RNCMs clinical intervention demonstrated significant A1C reduction (~2%). This is an important finding for health care policy makers for planning interventions with respect to long-term management of diabetes mellitus. PMID- 26856515 TI - Hepatitis-related stigma in chronic patients: A qualitative study. AB - BACKGROUND: Hepatitis is one of health problems throughout the world. It has numerous consequences on patients' life. Stigma, depression, social marginalization and financial problems are some of the challenges in these patients. AIM: The purpose of this qualitative study was to examine hepatitis related stigma and discrimination in patients living with chronic hepatitis in Iranian society. METHODS: This present study was designed as a qualitative method, and this article shows up the results of a qualitative research study undertaken with patients living with hepatitis in Iran. The study uses a content analysis method. A purposive sample of 18 patients was chosen. Data were collected through a semi-structured interview and field note that the researchers will take during participants' observation. Data analysis process was performed on the texts which were generated from verbatim transcripts of the participants interviews. RESULTS: Participants were between 18 and 61 years old. The main theme, Stigma, emerged from three themes during the process data analysis in this study. These themes were including fear to lose of family and social support, fear to present in public and fear of transmission. CONCLUSIONS: This research indicates that stigma presents major challenges not only for patients living with chronic hepatitis but also for nurses, other healthcare practitioners, family and social networks, institutions and society. The researcher suggests that interventions to reduce or eliminate stigma should require individual, structural, cultural thought, society and systemic changes. PMID- 26856516 TI - Empowering knowledge and its connection to health-related quality of life: A cross-cultural study: A concise and informative title: Empowering knowledge and its connection to health-related quality of life. AB - AIMS: Assess the association between patient education (i.e. empowering knowledge) and preoperative health-related quality of life, 6 months postoperative health-related quality of life, and the increase in health-related quality of life in osteoarthritis patients who underwent total hip or total knee arthroplasty. METHOD: This is a cross-cultural comparative follow-up study using structured instruments to measure the difference between expected and received patient education and self-reported health-related quality of life (EQ-5D) in Finland, Greece, Iceland, Spain and Sweden. RESULTS: The health-related quality of life was significantly increased 6 months postoperatively in all countries due to the arthroplasties. In the total sample, higher levels of empowering knowledge were associated with a higher health-related quality of life, both pre- and postoperatively, but not with a higher increase in health-related quality of life. On the national level, postoperative health-related quality of life was associated with higher levels of empowering knowledge in Finland, Iceland and Sweden. The increase in health-related quality of life was associated with levels of empowering knowledge for Greece. CONCLUSIONS: Overall, it can be concluded that the level of empowering knowledge was associated with high postoperative health-related quality of life in the total sample, even though there is some variation in the results per country. PMID- 26856517 TI - Comparing the effect of swaddling and breastfeeding and their combined effect on the pain induced by BCG vaccination in infants referring to Motahari Hospital, Jahrom, 2010-2011. AB - BACKGROUND AND AIM: Despite the clinical importance of pain, many neonates are subjected to numerous painful invasive procedures and their complications as part of their care. This study has been designed to investigate the effect of swaddling and breastfeeding, and their combined effect on the pain induced by BCG vaccination in healthy term infants. METHOD: This randomized double-blind intervention study was performed on 131 healthy term neonates in Motahari Hospital of Jahrom. The samples were randomly assigned into three intervention groups and a control group. The infants in the swaddled group were swaddled 2 minutes before and 2 minutes after vaccination. The infants in the breastfed group were breastfed within 45 minutes before vaccination. The infants in the combination group were both breast fed before and swaddled within vaccination but the infants in the control group were vaccinated without any intervention. Heart rate and oxygen saturation level of neonates were recorded in the 3 phases of: baseline, injection and 2 minutes after injection. Furthermore, the neonates' faces were recorded using a video camera. Then pain intensity was measured by Neonatal Facial Coding System (NFCS). Mean Score of pain intensity and physiological responses of subjects were statistically analyzed using non parametrical Kruskal-Wallis test and Mann-Whitney. RESULTS: The mean of pain intensity (NFCS) and changes in the heart rate at injection time to the baseline in the three intervention groups in comparison with the control group showed statistically significant difference (p=0.003 and p=0.002 respectively). However changes in blood oxygen saturation level, were not statistically significant difference between four groups. CONCLUSION: Regarding to the significant impact of both breastfeeding and swaddling on the pain reduction of vaccination, it is recommended to take benefit of these two safe and available non-pharmacological methods in order to relief pain during painful procedures. PMID- 26856518 TI - Barriers to primary care hospital follow-up among older adults in rural or semi rural communities. AB - BACKGROUND: Failure to follow-up with a primary care provider (PCP) following discharge from an acute care setting is strongly associated with readmission within 90 days among elderly patients. AIM: The purpose of this study was to identify barriers to primary care follow-up among older adults in rural communities. METHODS: This was an explanatory mixed methods study which included scaled survey and interview techniques. Descriptive and inferential statistics were calculated for scaled concepts. Standard content analysis was performed on the qualitative items. RESULTS: Correlation between intention to follow-up with a PCP and actual follow-up was poor (r=0.20). Patients encountered substantial obstacles to the PCP follow-up visit. Obstacles clustered into two groups: 1) healthcare or social system barriers and 2) personal characteristics of patients. CONCLUSIONS: Individualized discharge planning that reflects the complexities of post-hospitalization adaptation for elders is most likely to be useful for ensuring PCP follow-up. PMID- 26856519 TI - Socio-emotional support in French hospitals: Effects on French nurses' and nurse aides' affective commitment. AB - In spite of the differences in human resource management (HRM) practices between the non-profit health care sector and business life, the majority of health care sector research appears to be based on the HRM (for human resources management) blueprint for business life staff policy and practice. This study is aimed to better understand the impact of workplace social support in the context of French hospitals. Concrete, the first objective of this article comprises a thorough conceptualization and operationalization of workplace social support (i.e. both professional and personal social support). Data were collected in a French hospital among a sample of 62 respondents (for the qualitative part of our study), and among a sample of 171 health care professionals (nurses and nurse aids) (for the quantitative part of our study). Our outcomes indicate that, especially, personal support given by one's supervisor is strongly and positively related to nurses' and nurse aides' affective commitment. After a discussion about the outcomes, followed by some recommendations for future research, the article concludes with some practical implications for management in hospitals. PMID- 26856520 TI - Methods to measure peripheral and central sensitization using quantitative sensory testing: A focus on individuals with low back pain. AB - Quantitative sensory testing can be used to assess peripheral and central sensitization; important factors that contribute to the individual's experience of pain and disability. Many studies use quantitative sensory testing in patients with low back pain to detect alterations in pain sensitivity, however, because investigators employ different protocols, interpretation of findings across studies can become problematic. The purpose of this article is to propose a standardized method of testing peripheral and central pain sensitization in patients with low back pain. Video clips are provided to demonstrate correct procedures for measuring the response to experimental pain using mechanical, thermal and pressure modalities. As nurse researchers and clinicians increase utilization of quantitative sensory testing to examine pain phenotypes, it is anticipated that more personalized methods for monitoring the trajectory of low back pain and response to treatment will improve outcomes for this patient population. PMID- 26856521 TI - Analysis of the transition process among family caregivers in a hospital in the region of Catalonia in Spain. AB - PURPOSE: The aim of this study is to explore and understand the experience of the adaptation process among family caregivers in hospitals, who have an active presence in hospital and are essential in ensuring proper patient care. METHODS: A qualitative phenomenological approach was used to gain a deeper understanding of caregivers' lived experiences. Data were collected using in-depth interviews to explore six caregivers' experiences of hospitalization. RESULTS: The caregivers' accounts highlight the different determining factors in the transition process of a chronically ill patient's family caregiver during the patient's time in hospital. The most important themes emerging from the analysis were the importance of cultural beliefs and attitudes, meaning of the situation, caregiver's training and knowledge, socio-economic status and the hospital as a community. These categories can be analyzed using transitions theory. CONCLUSIONS: The most important conclusion is that the hospital in this study was not designed to accommodate caregivers, and the mechanisms used to meet caregivers' needs endanger their privacy, health, and coexistence in the hospital's rooms. Transitions theory provides a holistic understanding of the experience of the family caregiver. PMID- 26856522 TI - Development of an inter-professional screening instrument for cancer patients' education process. AB - AIM: The aim of this paper is to describe the development of an inter professional screening instrument for cancer patients' cognitive resources, knowledge expectations and inter-professional collaboration within patient education. DESIGN AND METHODS: Four empirical datasets during 2012-2014 were analyzed in order to identify main categories, subcategories and items for inter professional screening instrument. FINDINGS: Our inter-professional screening instrument integrates the critical moments of cancer patient education and the knowledge expectation types obtained from patient datasets to assessment of patients' cognitive resources, knowledge expectations and comprehension; and intra; and inter-professional. PMID- 26856523 TI - Application of telenursing in nursing practice: an integrative literature review. AB - AIMS AND BACKGROUND: Telenursing is the use of technological resources and communication systems to encourage the development of nursing. Its efficiency has been demonstrated to help countries overcome barriers to healthcare. This study investigates the current telenursing strategies utilized in nursing practice, as found in the literature. METHOD: Integrative literature review of the application of telenursing, using the descriptors: telenursing, nursing care and communication means, in Portuguese, English and Spanish, between 2003 and 2013. RESULTS: Telenursing is found particularly in care through telephone use for health services and orientations. The country with the largest number of research publications was the United States with 14 (37.8%), followed by Canada and the United Kingdom. FINAL CONSIDERATIONS: It could be verified that telenursing is growing, in view of its presence in different countries, with strong evidence and benefits of its use. It proves to be an efficient tool to help countries overcome geographical barriers and provide health care information to the population. PMID- 26856524 TI - Distinctions Between Research, Evidence Based Practice, and Quality Improvement. PMID- 26856525 TI - Biosimilars and cancer treatment of older patients. AB - Biosimilar monoclonal antibodies are being developed globally to meet clinical demand in oncology and potentially provide greater access to biologic therapies for patients with cancer, including older patients. In this supplement, we present an overview of the development, approval requirements, and characteristics of biosimilar monoclonal antibodies that may help practicing oncologists and other healthcare providers to acquire familiarity with this new group of therapeutic biologic agents. Furthermore, we review and discuss some of the challenges and potential strategies for the management of older patients with cancer, who represent an increasing population in many countries. PMID- 26856526 TI - Amoxicillin-loaded electrospun nanocomposite membranes for dental applications. AB - Electrospun nanocomposite matrices based on poly(epsilon-caprolactone) (PCL), nano-hydroxyapatite (nHAp) and amoxicillin (AMX) were designed and investigated for dental applications. nHAp provides good biocompatibility, bioactivity, osteoconductivity, and osteoinductivity properties, and AMX, as antibiotic model, controls and/or reduces bacterial contamination of periodontal defects while enhancing tissue regeneration. A series of polymeric nanocomposites was obtained by varying both the antibiotic and nHAp contents. Fibrous membranes of different compositions were obtained by electrospinning technique, and morphological, thermal, mechanical and surface properties were characterized. The incorporation of AMX seemed to alter the nHAp distribution within the microfibrous matrix. The interaction between AMX and nHAp affected the mechanical performance and modulated the antibiotic release behavior. AMX release profiles presented a burst release that depended on nHAp content, followed by a slow release stage where the drug content (85-100%) was released in 3 weeks. The antimicrobial activity of the AMX-loaded membranes was tested with four bacterial strains depended on both the drug and nHAp contents. Extensive mineralization in simulated body fluid (SBF) was evidenced by SEM/EDX analysis after 21 days. The studied electrospun nanocomposite amoxicillin-loaded membranes could be a promising fibrous-based antibiotic carrier system for dental and tissue engineering applications. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 966 976, 2017. PMID- 26856527 TI - Quadrivalent HPV vaccine effectiveness against high-grade cervical lesions by age at vaccination: A population-based study. AB - Human papillomavirus (HPV) types 16/18, included in HPV vaccines, contribute to the majority of cervical cancer, and a substantial proportion of cervical intraepithelial neoplasia (CIN) grades 2/3 or worse (CIN2+/CIN3+) including adenocarcinoma in situ or worse. The aim of this study was to quantify the effect of quadrivalent HPV (qHPV) vaccination on incidence of CIN2+ and CIN3+. A nationwide cohort of girls and young women resident in Sweden 2006-2013 and aged 13-29 (n = 1,333,691) was followed for vaccination and histologically confirmed high-grade cervical lesions. Data were collected using the Swedish nationwide healthcare registers. Poisson regression was used to calculate incidence rate ratios (IRRs) and vaccine effectiveness [(1-IRR)x100%] comparing fully vaccinated with unvaccinated individuals. IRRs were adjusted for attained age and parental education, and stratified on vaccination initiation age. Effectiveness against CIN2+ was 64% (IRR = 0.36, 95%CI = 0.27-0.47) for those initiating vaccination before age 17, and 25% (IRR = 0.75, 95%CI = 0.66-0.86) and 14% (IRR = 0.86, 95%CI = 0.73-1.01) for those initiating vaccination at ages 17-19, and at ages 20-29, respectively. Vaccine effectiveness against CIN3+ was similar to vaccine effectiveness against CIN2+. Results were robust for both women participating to the organized screening program and for women at prescreening ages. We show high effectiveness of qHPV vaccination on CIN2+ and CIN3+ lesions, with greater effectiveness observed in girls younger at vaccination initiation. Continued monitoring of impact of HPV vaccination in the population is needed in order to evaluate both long-term vaccine effectiveness and to evaluate whether the vaccination program achieves anticipated effects in prevention of invasive cervical cancer. PMID- 26856529 TI - Coenzyme-like ligands for affinity isolation of cholesterol oxidase. AB - Two coenzyme-like chemical ligands were designed and synthesized for affinity isolation of cholesterol oxidase (COD). To simulate the structure of natural coenzyme of COD (flavin adenine dinucleotide (FAD)), on Sepharose beads, 5 aminouracil, cyanuric chloride and 1, 4-butanediamine were composed and then modified. The COD gene from Brevibacterium sp. (DQ345780) was expressed in Escherichia coli BL21 (DE3), and then the sorbents were applied to adsorption analysis with the pure enzyme. Subsequently, the captured enzyme was applied to SDS-PAGE and activity analysis. As calculated, the theoretical maximum adsorption (Qmax) of the two affinity sorbents (RL-1 and RL-2) were ~83.5 and 46.3mg/g wet gel; and the desorption constant Kd of the two sorbents were ~6.02*10(-4) and 1.19*10(-4)MUM. The proteins after cell lysis were applied to affinity isolation, and then after one step of affinity binding on the two sorbents, the protein recoveries of RL-1 and RL-2 were 9.2% and 9.7%; the bioactivity recoveries were 92.7% and 91.3%, respectively. SDS-PAGE analysis revealed that the purities of COD isolated with the two affinity sorbents were approximately 95%. PMID- 26856530 TI - The Risk of Prion Infection through Bovine Grafting Materials. AB - BACKGROUND: Bovine-derived grafting materials are frequently used in a variety of bone augmentation techniques. The aim of this paper is to assess the unique safety issue of bovine-derived grafting materials that is rarely addressed in dental literature: risk of bovine spongiform encephalopathy (BSE). METHODS: The validity of the current BSE diagnostic methods, surveillance and epidemiological trends in affected countries, and BSE infectivity in bovine bone before and after manufacturing processing were reviewed and analyzed. RESULTS: Prion screening has significant limits. Humans are not safe from the infection of prion disease of other species. Prions can and do break the species barrier. There is evidence there may be tens of thousands of infectious carriers in the western countries alone. This raises concern about the potential for perpetuation of infection via medical procedures. CONCLUSION: The limited ability to screen prions within the animal genome, along with a long latency period to manifestation of the disease (1 to over 50 years) in infected patients, provides a framework for discussing posible long-term risks of the xenografts that are used so extensively in dentistry. We suggest abolishing the use of bovine bone. PMID- 26856531 TI - Systematic characterization of the metabolites of echinacoside and acteoside from Cistanche tubulosa in rat plasma, bile, urine and feces based on UPLC-ESI-Q-TOF MS. AB - Echinacoside (ECH) and acteoside (ACT), as the most and major active components of Cistanche tubulosa, were reported to possess cardioactive, neuroprotective and hepatocyte protective effects, as well as antibacterial, antioxidative effects. Recently, more studies have focused on their pharmacological activities. However, their metabolic profiles in vivo have not been sufficiently investigated. This study proposes an approach for rapidly identifying the complicated and unpredictable metabolites of ECH and ACT in rat plasma, bile, urine and feces, and systematically and comprehensively revealing their major metabolic pathways, based on powerful ultra-high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Plasma, bile, urine and feces were collected from rats after a single 200 mg/kg oral dose. A total of 49 metabolites were detected in rat biological samples. Through analyzing metabolites in bile samples, it was found that ECH and ACT were subjected to a marked hepatic first-pass effect in liver. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26856532 TI - Failing to Fix What is Found: Risk Accommodation in the Oil and Gas Industry. AB - The present program of research synthesizes the findings from three studies in line with two goals. First, the present research explores how the oil and gas industry is performing at risk mitigation in terms of finding and fixing errors when they occur. Second, the present research explores what factors in the work environment relate to a risk-accommodating environment. Study 1 presents a descriptive evaluation of high-consequence incidents at 34 oil and gas companies over a 12-month period (N = 873), especially in terms of those companies' effectiveness at investigating and fixing errors. The analysis found that most investigations were fair in terms of quality (mean = 75.50%), with a smaller proportion that were weak (mean = 11.40%) or strong (mean = 13.24%). Furthermore, most companies took at least one corrective action for high-consequence incidents, but few of these corrective actions were confirmed as having been completed (mean = 13.77%). In fact, most corrective actions were secondary interim administrative controls (e.g., having a safety meeting) rather than fair or strong controls (e.g., training, engineering elimination). Study 2a found that several environmental factors explain the 56.41% variance in safety, including management's disengagement from safety concerns, finding and fixing errors, safety management system effectiveness, training, employee safety, procedures, and a production-over-safety culture. Qualitative results from Study 2b suggest that a compliance-based culture of adhering to liability concerns, out-group blame, and a production-over-safety orientation may all impede safety effectiveness. PMID- 26856528 TI - Cool night-time temperatures induce the expression of CONSTANS and FLOWERING LOCUS T to regulate flowering in Arabidopsis. AB - Day length and ambient temperature are major stimuli controlling flowering time. To understand flowering mechanisms in more natural conditions, we explored the effect of daily light and temperature changes on Arabidopsis thaliana. Seedlings were exposed to different day/night temperature and day-length treatments to assess expression changes in flowering genes. Cooler temperature treatments increased CONSTANS (CO) transcript levels at night. Night-time CO induction was diminished in flowering bhlh (fbh)-quadruple mutants. FLOWERING LOCUS T (FT) transcript levels were reduced at dusk, but increased at the end of cooler nights. The dusk suppression, which was alleviated in short vegetative phase (svp) mutants, occurred particularly in younger seedlings, whereas the increase during the night continued over 2 wk. Cooler temperature treatments altered the levels of FLOWERING LOCUS M-beta (FLM-beta) and FLM-delta splice variants. FT levels correlated strongly with flowering time across treatments. Day/night temperature changes modulate photoperiodic flowering by changing FT accumulation patterns. Cooler night-time temperatures enhance FLOWERING BHLH (FBH)-dependent induction of CO and consequently increase CO protein. When plants are young, cooler temperatures suppress FT at dusk through SHORT VEGETATIVE PHASE (SVP) function, perhaps to suppress precocious flowering. Our results suggest day length and diurnal temperature changes combine to modulate FT and flowering time. PMID- 26856533 TI - A survey of platelet aggregometry tests in a tertiary centre. PMID- 26856536 TI - Erratum to: NGF eye-drops topical administration in patients with retinitis pigmentosa, a pilot study. PMID- 26856535 TI - Resistance related metabolic pathways for drug target identification in Mycobacterium tuberculosis. AB - BACKGROUND: Increasing resistance to anti-tuberculosis drugs has driven the need for developing new drugs. Resources such as the tropical disease research (TDR) target database and AssessDrugTarget can help to prioritize putative drug targets. Hower, these resources do not necessarily map to metabolic pathways and the targets are not involved in dormancy. In this study, we specifically identify drug resistance pathways to allow known drug resistant mutations in one target to be offset by inhibiting another enzyme of the same metabolic pathway. One of the putative targets, Rv1712, was analysed by modelling its three dimensional structure and docking potential inhibitors. RESULTS: We mapped 18 TB drug resistance gene products to 15 metabolic pathways critical for mycobacterial growth and latent TB by screening publicly available microarray data. Nine putative targets, Rv1712, Rv2984, Rv2194, Rv1311, Rv1305, Rv2195, Rv1622c, Rv1456c and Rv2421c, were found to be essential, to lack a close human homolog, and to share >67 % sequence identity and >87 % query coverage with mycobacterial orthologs. A structural model was generated for Rv1712, subjected to molecular dynamic simulation, and identified 10 compounds with affinities better than that for the ligand cytidine-5'-monophosphate (C5P). Each compound formed more interactions with the protein than C5P. CONCLUSIONS: We focused on metabolic pathways associated with bacterial drug resistance and proteins unique to pathogenic bacteria to identify novel putative drug targets. The ten compounds identified in this study should be considered for experimental studies to validate their potential as inhibitors of Rv1712. PMID- 26856534 TI - Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia- can findings from animal models be translated to humans? AB - BACKGROUND: Cachexia is a multi-factorial, systemic syndrome that especially affects patients with cancer of the gastrointestinal tract, and leads to reduced treatment response, survival and quality of life. The most important clinical feature of cachexia is the excessive wasting of skeletal muscle mass. Currently, an effective treatment is still lacking and the search for therapeutic targets continues. Even though a substantial number of animal studies have contributed to a better understanding of the underlying mechanisms of the loss of skeletal muscle mass, subsequent clinical trials of potential new drugs have not yet yielded any effective treatment for cancer cachexia. Therefore, we questioned to which degree findings from animal studies can be translated to humans in clinical practice and research. DISCUSSION: A substantial amount of animal studies on the molecular mechanisms of muscle wasting in cancer cachexia has been conducted in recent years. This extensive review of the literature showed that most of their observations could not be consistently reproduced in studies on human skeletal muscle samples. However, studies on human material are scarce and limited in patient numbers and homogeneity. Therefore, their results have to be interpreted critically. More research is needed on human tissue samples to clarify the signaling pathways that lead to skeletal muscle loss, and to confirm pre-selected drug targets from animal models in clinical trials. In addition, improved diagnostic tools and standardized clinical criteria for cancer cachexia are needed to conduct standardized, randomized controlled trials of potential drug candidates in the future. PMID- 26856539 TI - Attention Disengagement Difficulties among Average Weight Women Who Binge Eat. AB - In this study, we assessed biases in attention disengagement among average-weight women with binge-eating (n = 33) and non-eating disordered controls (n = 31). Participants engaged in a spatial cueing paradigm task wherein they first observed high-calorie food, low-calorie food, or neutral images and then had to quickly locate targets in either the same or a different location. Within both groups, reaction times (RTs) were longer to valid-cued trials (i.e. target appearing in location of preceding cue) than to invalid-cued trials (i.e. targets appearing in location different from initial location), reflecting a general inhibition of return (IOR) effect. However, RT findings also indicated that women with BE had significantly more difficulty disengaging from high-calorie food images than did controls, even though neither group had disengagement problems related to other image types. Selective attention disengagement difficulties related to high-calorie food images suggested that increased reward sensitivity to such cues is related to binge eating risk. Copyright (c) 2016 John Wiley & Sons, Ltd and Eating Disorders Association. PMID- 26856537 TI - Inter-tissue coexpression network analysis reveals DPP4 as an important gene in heart to blood communication. AB - BACKGROUND: Inter-tissue molecular interactions are critical to the function and behavior of biological systems in multicellular organisms, but systematic studies of interactions between tissues are lacking. Also, existing studies of inter tissue interactions are based on direct gene expression correlations, which can't distinguish correlations due to common genetic architectures versus biochemical or molecular signal exchange between tissues. METHODS: We developed a novel strategy to study inter-tissue interaction by removing effects of genetic regulation of gene expression (genetic decorrelation). We applied our method to the comprehensive atlas of gene expression across nine human tissues in the Genotype-Tissue Expression (GTEx) project to generate novel genetically decorrelated inter-tissue networks. From this we derived modules of genes important in inter-tissue interactions that are likely driven by biological signal exchange instead of their common genetic basis. Importantly we highlighted communication between tissues and elucidated gene activities in one tissue inducing gene expression changes in others. RESULTS: We reveal global unidirectional inter-tissue coordination of specific biological pathways such as protein synthesis. Using our data, we highlighted a clinically relevant example whereby heart expression of DPP4 was coordinated with a gene expression signature characteristic for whole blood proliferation, potentially impacting peripheral stem cell mobilization. We also showed that expression of the poorly characterized FOCAD in heart correlated with protein biosynthetic processes in the lung. CONCLUSIONS: In summary, this is the first resource of human multi tissue networks enabling the investigation of molecular inter-tissue interactions. With the networks in hand, we may systematically design combination therapies that simultaneously target multiple tissues or pinpoint potential side effects of a drug in other tissues. PMID- 26856538 TI - AMP-activated protein kinase contributes to zinc-induced neuronal death via activation by LKB1 and induction of Bim in mouse cortical cultures. AB - BACKGROUND: We reported that zinc neurotoxicity, a key mechanism of ischemic neuronal death, was mediated by poly ADP-ribose polymerase (PARP) over-activation following NAD(+)/ATP depletion in cortical cultures. Because AMP-activated protein kinase (AMPK) can be activated by ATP depletion, and AMPK plays a key role in excitotoxicity and ischemic neuronal death, we examined whether AMPK could be involved in zinc neurotoxicity in mouse cortical neuronal cultures. RESULTS: Compound C, an AMPK inhibitor, significantly attenuated zinc-induced neuronal death. Activation of AMPK was detected beginning 2 h after a 10-min exposure of mouse cortical neurons to 300 MUM zinc, although a significant change in AMP level was not detected until 4 h after zinc treatment. Thus, AMPK activation might not have been induced by an increase in intracellular AMP in zinc neurotoxicity. Furthermore, we observed that liver kinase B1 (LKB1) but not Ca(2+)/calmodulin-dependent protein kinase kinase beta (CaMKKbeta), was involved in AMPK activation. Although STO-609, a chemical inhibitor of CaMKKbeta, significantly attenuated zinc neurotoxicity, zinc-induced AMPK activation was not affected, which suggested that CaMKKbeta was not involved in AMPK activation. Knockdown of LKB1 by siRNA significantly reduced zinc neurotoxicity, as well as zinc-induced AMPK activation, which indicated a possible role for LKB1 as an upstream kinase for AMPK activation. In addition, mRNA and protein levels of Bim, a pro-apoptotic Bcl-2 family member, were noticeably increased by zinc in an AMPK dependent manner. Finally, caspase-3 activation in zinc-induced neuronal death was mediated by LKB1 and AMPK activation. CONCLUSIONS: The results suggested that AMPK mediated zinc-induced neuronal death via up-regulation of Bim and activation of caspase-3. Rapid activation of AMPK was detected after exposure of cortical neuronal cultures to zinc, which was induced by LKB1 activation but not increased intracellular AMP levels or CaMKKbeta activation. Hence, blockade of AMPK in the brain may protect against zinc neurotoxicity, which is likely to occur after acute brain injury. PMID- 26856540 TI - Surgical anatomy of the sciatic nerve: A meta-analysis. AB - The sciatic nerve has varying anatomy with respect to the piriformis muscle. Understanding this variant anatomy is vital to avoiding iatrogenic nerve injuries. A comprehensive electronic database search was performed to identify articles reporting the prevalence of anatomical variations or morphometric data of the sciatic nerve. The data found was extracted and pooled into a meta analysis. A total of 45 studies (n = 7068 lower limbs) were included in the meta analysis on the sciatic nerve variations with respect to the piriformis muscle. The normal Type A variation, where the sciatic nerve exits the pelvis as a single entity below the piriformis muscle, was most common with a pooled prevalence of 85.2% (95%CI: 78.4-87.0). This was followed by Type B with a pooled prevalence of 9.8% (95%CI: 6.5-13.2), where the sciatic nerve bifurcated in the pelvis with the exiting common peroneal nerve piercing, and the tibial nerve coursing below the piriformis muscle. In morphometric analysis, we found that the pooled mean width of the sciatic nerve at the lower margin of the piriformis muscle was 15.55 mm. The pooled mean distance of sciatic nerve bifurcation from the popliteal fossa was 65.43 mm. The sciatic nerve deviates from its normal course of pelvic exit in almost 15% of cases. As such we recommend that a thorough assessment of sciatic nerve variants needs to be considered when performing procedures in the pelvic and gluteal regions in order to reduce the risk of iatrogenic injury. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1820-1827, 2016. PMID- 26856541 TI - Individual differences in in vitro and in vivo metabolic clearances of antipsychotic risperidone from Japanese subjects genotyped for cytochrome P450 2D6 and 3A5. AB - OBJECTIVE: There are conflicting reports regarding the effects of cytochrome P450 (P450, CYP) genotypes on the plasma concentrations of risperidone and its pharmacologically active metabolite, 9-hydroxyrisperidone (paliperidone), in clinical patients. The aim of this study was to investigate individual differences in the metabolic clearance of risperidone in vitro and in vivo. METHODS: In vitro liver microsomal risperidone 9-hydroxylation activities and in vivo plasma concentrations of risperidone and paliperidone were investigated in 15 male and 12 female Japanese subjects (mean age 52 years, range: 24-75 years) genotyped for CYP2D6 and CYP3A5. RESULTS: CYP2D6 intermediate and poor metabolizers showed significantly lower liver microsomal risperidone 9 hydroxylation activities than extensive metabolizers did at 5 MUM of risperidone; this difference was not evident at 50 MUM of risperidone. The recombinant CYP3A5 Vmax/Km value for risperidone 9-hydroxylation was 30% that of CYP3A4, and liver microsomes from CYP3A5 expressers had similar risperidone 9-hydroxylation activities to those of CYP3A5 poor expressers. The plasma concentration/dose ratios for risperidone and paliperidone in 27 Japanese patients were not significantly influenced by the CYP2D6 or CYP3A5 genotypes. CONCLUSIONS: Individual differences in metabolic clearance of risperidone under the present conditions were not significantly influenced by the genotypes of CYP2D6 or CYP3A5. PMID- 26856542 TI - Endoscopic ultrasound-guided ablation of branch-duct intraductal papillary mucinous neoplasms: Feasibility and safety tests using porcine gallbladders. AB - BACKGROUND AND AIM: Radiofrequency ablation (RFA) and ethanol ablation are accepted methods of tissue destruction for treating cystic tumors. The aim of the present study was to evaluate the feasibility, efficacy, and safety of endoscopic ultrasound (EUS)-guided ablation using normal porcine gallbladders as a substitute model for branch-duct intraductal papillary mucinous neoplasms (BD IPMN). METHODS: Six adult mini pigs were included in this prospective study. EUS guided RFA with or without ethanol ablation of the gallbladder was carried out using a prototype 18-gauge endoscopic RFA electrode, and RFA and ethanol ablation were done in a single session. Outcomes were assessed in terms of macroscopic and microscopic evaluations of the treated gallbladders. RESULTS: The prototype RFA electrode was used for ablation of the mucosa, aspiration of the internal contents of the gallbladder, and ethanol injection. RFA plus ethanol lavage resulted in a greater mean percentage of denuded gallbladder mucosa (97.5%) than RFA alone (55.8%). Effects of ablation extending to the cystic duct and partially denuded cystic duct mucosae were detected in five of the six pigs. There were no major procedure-related adverse events. CONCLUSIONS: EUS-guided ablation of the gallbladder mucosa was feasible and effective in the porcine model. Additional studies will be required to fully assess the risk of procedure-related damage to the main pancreatic duct before using this technique in a clinical setting. PMID- 26856543 TI - Should 30 letters be added to the 4 m visual acuity score on the Early Treatment Diabetic Retinopathy Study Chart? PMID- 26856545 TI - Metastatic Crohn's disease in pediatrics. AB - INTRODUCTION AND OBJECTIVES: Metastatic Crohn's disease (MCD) is an extraintestinal manifestation of Crohn's disease, with biopsy as fundamental diagnostic tool. There are few references to MCD in children, with a 0.5-1% estimated incidence in adults. There is no consensus about its therapeutic approach. We describe our diagnostic and therapeutic experience in MCD. RESULTS: Four cases of MCD are described in our Pediatric Gastroenterology Unit in a tertiary care hospital. The age at diagnosis was between 7 and 13 years. Lesions appeared before the diagnosis of Crohn's disease in three of them, and during the course of the disease in another one, with genital location in three patients and bilateral pretibial region in the other. All four cases demonstrated non caseificant granulomas on biopsy. Only two patients used exclusive enteral nutrition therapy with complete resolution, while other two cases received a combination of therapies (corticosteroids, azathioprine, tacrolimus, infliximab and adalimumab) because of recurrence. Only one case required surgery after poor clinical control. CONCLUSION: The MCD is infrequent but must always be included in the differential diagnosis of cutaneous lesions in Crohn's disease, considering it could be the debut of the disease. We will rely on biopsy anyway for definitive diagnosis. In this series the genital region is verified as the most commonly affected in children. The therapeutic approach does not differ from the management of intestinal involvement. PMID- 26856544 TI - Role of COX-2-derived PGE2 on vascular stiffness and function in hypertension. AB - BACKGROUND AND PURPOSE: Prostanoids derived from COX-2 and EP receptors are involved in vascular remodelling in different cardiovascular pathologies. This study evaluates the contribution of COX-2 and EP1 receptors to vascular remodelling and function in hypertension. EXPERIMENTAL APPROACH: Spontaneously hypertensive rats (SHR) and angiotensin II (AngII)-infused (1.44 mg . kg(-1) . day(-1), 2 weeks) mice were treated with the COX-2 inhibitor celecoxib (25 mg . kg(-1) . day(-1) i.p) or with the EP1 receptor antagonist SC19220 (10 mg . kg(-1) . day(-1) i.p.). COX-2(-/-) mice with or without AngII infusion were also used. KEY RESULTS: Celecoxib and SC19220 treatment did not modify the altered lumen diameter and wall : lumen ratio in mesenteric resistance arteries from SHR infused and/or AngII-infused animals. However, both treatments and COX-2 deficiency decreased the augmented vascular stiffness in vessels from hypertensive animals. This was accompanied by diminished vascular collagen deposition, normalization of altered elastin structure and decreased connective tissue growth factor and plasminogen activator inhibitor-1 gene expression. COX-2 deficiency and SC19220 treatment diminished the increased vasoconstrictor responses and endothelial dysfunction induced by AngII infusion. Hypertensive animals showed increased mPGES-1 expression and PGE2 production in vascular tissue, normalized by celecoxib. Celecoxib treatment also decreased AngII-induced macrophage infiltration and TNF-alpha expression. Macrophage conditioned media (MCM) increased COX-2 and collagen type I expression in vascular smooth muscle cells; the latter was reduced by celecoxib treatment. CONCLUSIONS AND IMPLICATIONS: COX-2 and EP1 receptors participate in the increased extracellular matrix deposition and vascular stiffness, the impaired vascular function and inflammation in hypertension. Targeting PGE2 receptors might have benefits in hypertension-associated vascular damage. PMID- 26856546 TI - Effect of the chelation of metal cation on the antioxidant activity of chondroitin sulfates. AB - The antioxidant potencies of chondroitin sulfates (CSs) from shark cartilage, salmon cartilage, bovine trachea, and porcine intestinal mucosa were compared by three representative methods for the measurement of the antioxidant activity; DPPH radical scavenging activity, superoxide radical scavenging activity, and hydroxyl radical scavenging activity. CSs from salmon cartilage and bovine trachea showed higher potency in comparison with CSs from shark cartilage and porcine intestinal mucosa. Next, CS from salmon cartilage chelating with Ca(2+), Mg(2+), Mn(2+), or Zn(2+) were prepared, and their antioxidant potencies were compared. CS chelating with Ca(2+) or Mg(2+) ions showed rather decreased DPPH radical scavenging activity in comparison with CS of H(+) form. In contrast, CS chelating with Ca(2+) or Mg(2+) ion showed remarkably enhanced superoxide radical scavenging activity than CS of H(+) or Na(+) form. Moreover, CS chelating with divalent metal ions, Ca(2+), Mg(2+), Mn(2+), or Zn(2+), showed noticeably higher hydroxyl radical scavenging activity than CS of H(+) or Na(+) form. The present results revealed that the scavenging activities of, at least, superoxide radical and hydroxyl radical were enhanced by the chelation with divalent metal ions. PMID- 26856547 TI - Collaborating on asthma care. PMID- 26856548 TI - Guidelines for intravenous fluids in children published. PMID- 26856549 TI - Grant awarded for research into sexual health of homeless young people living in hostels. PMID- 26856551 TI - Competition winner will be our voice for students. PMID- 26856552 TI - Children's nursing education to be given spring overhaul. PMID- 26856553 TI - Primary care staff should train to work with children. PMID- 26856555 TI - 'Lifesaving' Tookie vest developed for cancer care. PMID- 26856554 TI - Students want meeting with Jeremy Hunt to debate bursaries. PMID- 26856557 TI - Outstanding children's nurses win recognition in new year's honours. PMID- 26856556 TI - Staff should be more aware of sepsis, says bereaved mother. PMID- 26856560 TI - Greater collaboration vital to treating asthma in the young. PMID- 26856561 TI - Making school nurses 'carer aware'. PMID- 26856566 TI - Funding sources and grant applications. PMID- 26856567 TI - How parents relate to adolescents living with a chronic disease. PMID- 26856570 TI - Student voice--Resilience. PMID- 26856572 TI - Authoritative overview. PMID- 26856573 TI - Are we ready for child refugees? PMID- 26856575 TI - Managing young people with self-harming or suicidal behaviour. AB - This literature review aimed to determine the risk factors being used to identify children and young people who are at increased risk of engaging in self-harm and suicidal behaviour, so that optimal care can be provided for this patient group in children's medical ward settings. The two main themes that emerged were mental and neurodevelopmental disorders, and external factors. Management strategies to aid healthcare professionals in caring for this patient group were also identified. The review concludes by highlighting the need to provide healthcare professionals with continuing education about the mental health problems of children and young people, including risk factors and management strategies. PMID- 26856574 TI - Diagnosis and nursing management of coeliac disease in children. AB - Coeliac disease is an autoimmune condition caused by the ingestion of gluten containing foods and affects about 1% of children and young people in the UK. Classic symptoms include diarrhoea, bloating, weight loss and abdominal pain. However, extra-intestinal manifestations, such as iron deficiency anaemia, faltering growth, delayed puberty and mouth ulcers, are increasingly being recognised. Some children have an increased risk of developing coeliac disease, such as a strong family history, certain genetic conditions and type 1 diabetes, therefore there is a need for increased awareness and early diagnosis before symptoms occur. If coeliac disease is suspected, a child should have serological screening with anti-tissue transglutaminase titres. Diagnosis is traditionally confirmed by a small bowel biopsy while the child remains on a 'normal' diet that does not exclude gluten. More recently, for a selective group of children, modification of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines has enabled non-biopsy (serological) diagnosis of coeliac disease. Children's nurses have an important role in recognising and diagnosing coeliac disease earlier as well as offering ongoing dietary support. Enabling children to maintain a gluten-free diet is essential for general wellbeing and preventing long-term complications. PMID- 26856576 TI - Educating children and families about growth hormone deficiency and its management: part 1. AB - The management of growth hormone deficiency is long term. Children may be diagnosed at pre-school age meaning relationships with the paediatric endocrine team may last more than 15 years. The education role of the paediatric endocrine nurse specialist is essential in working in partnership with families over a long period of time. Children and young people have changing needs for information to help them understand their condition and growth hormone deficiency treatment as they grow up. Developing positive working relationships with parents, children and young people enables their developmental needs and the context in which they live their lives to be central to any educational planning for them. Addressing developmental needs when providing information on growth hormone deficiency to children and young people reinforces the need for education to be an ongoing process and not a one-off event. This is part one of a two-part article. The second part will be published in the March issue of Nursing Children and Young People and it focuses on educating children, young people and their parents about the condition, and includes case studies. PMID- 26856577 TI - Living the dream. PMID- 26856580 TI - Erratum to: Effects of Balance Training on Balance Performance in Healthy Older Adults: A Systematic Review and Meta-analysis. PMID- 26856578 TI - The effects of prenatal genetic analysis on fetuses born to carrier mothers with primary immunodeficiency diseases. AB - OBJECTIVE: Prenatal genetic analysis in primary immunodeficiency diseases (PIDs) can decrease morbidity and mortality. METHODS: We compared the postnatal prognoses of index cases and their subsequent sibling-fetuses using prenatal genetic analysis. RESULTS: From 2007 to 2014, 14 sibling-fetuses receiving a prenatal diagnosis born to four mothers with WAS, three with X-CGD, and one each with IPEX, XLA and severe combined immunodeficiency [RAG2-SCID] were recruited. There were six affected, two carriers, and six wild types. Among the six affected, four [3X-CGD and 1RAG2-SCID] were terminated and two [1WAS and 1X-CGD] with early prophylactics underwent successful hematopoietic stem cell transplantation (HSCT) without infection. In the 12 index cases with a postnatal diagnosis, eight died (five due to infections and one each due to refractory bleeding, severe diarrhea, and post-transplant pneumothorax), two X-CGD underwent reconstituted HSCT after recurrent life-threatening infections, one WAS developed malignancy, and another WAS developed autoimmune disorders despite the administration of prophylactics and regular immunoglobulin infusion. CONCLUSION: Instead of recurrent life-threatening infections leading to mortality in the postnatal diagnosis group, the severe PIDs who received early prophylactics were cured by HSCT, and all of mortality were terminations in the prenatal diagnosis group. Further large-scale studies are needed to validate this beneficial effect. Key message Prenatal genetic analysis in fetuses born to PIDs carrier mothers allows for the affected fetuses to receive optimal management including prophylactics against infections and HSCT if indicated. Patients with PIDs diagnosed postnatally who are prone to severe infections have higher rates of morbidity and mortality than their subsequent siblings who have a prenatal genetic diagnosis. PMID- 26856581 TI - New concepts of microbial treatment processes for the nitrogen removal: effect of protein and amino acids degradation. AB - High concentrations of proteins and amino acids can be found in wastewater and wastewater stream produced in anaerobic digesters, having shown that amino acids could persist over different managements for nitrogen removal affecting the nitrogen removal processes. Nitrogen removal is completely necessary because of their implications and the significant adverse environmental impact of ammonium such as eutrophication and toxicity to aquatic life on the receiving bodies. In the last decade, the treatment of effluents with high ammonium concentration through anammox-based bioprocesses has been enhanced because these biotechnologies are cheaper and more environmentally friendly than conventional technologies. However, it has been shown that the presence of important amounts of proteins and amino acids in the effluents seriously affects the microbial autotrophic consortia leading to important losses in terms of ammonium oxidation efficiency. Particularly the presence of sulfur amino acids such as methionine and cysteine has been reported to drastically decrease the autotrophic denitrification processes as well as affect the microbial community structure promoting the decline of ammonium oxidizing bacteria in favor of other phylotypes. In this context we discuss that new biotechnological processes that improve the degradation of protein and amino acids must be considered as a priority to increase the performance of the autotrophic denitrification biotechnologies. PMID- 26856582 TI - Evidence does not support the alkaline diet. PMID- 26856583 TI - Response to Fenton and Fenton: evidence does not support the alkaline diet. PMID- 26856584 TI - Changes in bone mineral density over time by body mass index in the health ABC study. AB - Obesity appears protective against osteoporosis in cross-sectional studies. However, results from this longitudinal study found that obesity was associated with bone loss over time. Findings underscore the importance of looking at the longitudinal relationship, particularly given the increasing prevalence and duration of obesity among older adults. INTRODUCTION: Cross-sectional studies have found a positive association between body mass index (BMI) and bone mineral density (BMD), but little is known about the longitudinal relationship in US older adults. METHODS: We examined average annual rate of change in BMD by baseline BMI in the Health, Aging, and Body Composition Study. Repeated measurement of BMD was performed with dual-energy X-ray absorptiometry (DXA) at baseline and years 3, 5, 6, 8, and 10. Multivariate generalized estimating equations were used to predict mean BMD (femoral neck, total hip, and whole body) by baseline BMI (excluding underweight), adjusting for covariates. RESULTS: In the sample (n = 2570), 43 % were overweight and 24 % were obese with a mean baseline femoral neck BMD of 0.743 g/cm(2), hip BMD of 0.888 g/cm(2), and whole body BMD of 1.09 g/cm(2). Change in total hip or whole-body BMD over time did not vary by BMI groups. However, obese older adults lost 0.003 g/cm(2) of femoral neck BMD per year more compared with normal weight older adults (p < 0.001). Femoral neck BMD change over time did not differ between the overweight and normal weight BMI groups (p = 0.74). In year 10, adjusted femoral neck BMD ranged from 0.696 g/cm(2) among obese, 0.709 g/cm(2) among normal weight, and 0.719 g/cm(2) among overweight older adults. CONCLUSIONS: Findings underscore the importance of looking at the longitudinal relationship between body composition and bone mineral density among older adults, indicating that high body mass may not be protective for bone loss over time. PMID- 26856585 TI - Impaired bone remodeling in children with osteogenesis imperfecta treated and untreated with bisphosphonates: the role of DKK1, RANKL, and TNF-alpha. AB - In this study, we investigated the bone cell activity in patients with osteogenesis imperfecta (OI) treated and untreated with neridronate. We demonstrated the key role of Dickkopf-1 (DKK1), receptor activator of nuclear factor-kappaB ligand (RANKL), and tumor necrosis factor alpha (TNF-alpha) in regulating bone cell of untreated and treated OI subjects. These cytokines could represent new pharmacological targets for OI. INTRODUCTION: Bisphosphonates are widely used in the treatment of children with osteogenesis imperfecta (OI) with the objective of reducing the risk of fractures. Although bisphosphonates increase bone mineral density in OI subjects, the effects on fracture incidence are conflicting. The aim of this study was to investigate the mechanisms underlying bone cell activity in subjects with mild untreated forms of OI and in a group of subjects with severe OI treated with cycles of intravenous neridronate. METHODS: Sclerostin, DKK1, TNF-alpha, RANKL, osteoprotegerin (OPG), and bone turnover markers were quantified in serum of 18 OI patients (12 females, mean age 8.86 +/- 3.90), 8 of which were receiving cyclic intravenous neridronate, and 21 sex- and age-matched controls. The effects on osteoblastogenesis and OPG expression of media conditioned by the serum of OI patients and anti-DKK1 neutralizing antibody were evaluated. Osteoclastogenesis was assessed in cultures from patients and controls. RESULTS: DKK1 and RANKL levels were significantly increased both in untreated and in treated OI subjects with respect to controls. The serum from patients with high DKK1 levels inhibited both osteoblast differentiation and OPG expression in vitro. High RANKL and low OPG messenger RNA (mRNA) levels were found in lymphomonocytes from patients. High amounts of TNF-alpha were expressed by monocytes, and an elevated percentage of circulating CD11b-CD51/CD61+ osteoclast precursors was observed in patients. CONCLUSIONS: Our study demonstrated the key role of DKK1, RANKL, and TNF-alpha in regulating bone cell activity of subjects with OI untreated and treated with bisphosphonates. These cytokines could represent new pharmacological targets for OI patients. PMID- 26856586 TI - Safety and clinical performance of kyphoplasty and SpineJack((r)) procedures in the treatment of osteoporotic vertebral compression fractures: a pilot, monocentric, investigator-initiated study. AB - Clinical performance and safety of two percutaneous vertebral cement augmentation (VA) procedures (SpineJack(r) and Kyphx Xpander(r) balloon) were compared in patients with osteoporotic compression fractures. Both techniques were safe, efficient, and led to a rapid and marked improvement in clinical signs; nevertheless, SpineJack showed better restoration of vertebral heights and angles, maintained over time. INTRODUCTION: In patients with osteoporotic vertebral compression fractures (VCFs), both SpineJack(r) (SJ) and balloon kyphoplasty (BKP) led to a rapid and marked improvement in clinical signs. This pilot, monocentric, investigator-initiated, prospective study aimed to compare two percutaneous vertebral augmentation procedures in the painful osteoporotic VCF treatment. METHODS: Thirty patients were randomized to receive SJ (n = 15) or BKP (n = 15). Analgesic consumption, back pain intensity (visual analog scale (VAS)), and Oswestry Disability Index (ODI) scores were recorded preoperatively, at 5 days and 1, 3, 6, and 12 months post-surgery. Quality of life (EQ-VAS score) was evaluated at 1, 3, 6, and 12 months. Spine X-rays were taken 48 h prior to procedure and 5 days and 6 and 12 months after. RESULTS: SpineJack(r) led to a significantly shorter intervention period (23 vs 32 min; p < 0.001), a strong, rapid, and long-lasting decline in pain (94 vs 82 % at 12 months) and in functional disability (94 vs 90 % at 12 months), a greater and sustainable mean correction of anterior (12 +/- 13 vs 0 +/- 7 % for BKP, p = 0.003) and central height (12 +/- 10 vs 2 +/- 6 % for BKP, p = 0.001) at 12 months, and a larger restoration of the vertebral body angle still evident 12 months after implantation (-4.4 degrees +/- 5.8 degrees vs 0.2 degrees +/- 3.0 degrees for BKP; p = 0.012). CONCLUSIONS: This pilot study showed that both techniques were safe and efficient for the osteoporotic VCF treatment. Radiological results indicate that the SpineJack(r) procedure has a higher potential for vertebral body height restoration and maintenance over time. PMID- 26856588 TI - A protocol for the isolation and cultivation of brown bear (Ursus arctos) adipocytes. AB - Brown bears (Ursus arctos) exhibit hyperphagia each fall and can become obese in preparation for hibernation. They do this without displaying the physiological problems typically seen in obese humans, such as Type 2 diabetes and heart disease. The study of brown bear hibernation biology could therefore aid in the development of novel methods for combating metabolic diseases. To this end, we isolated mesenchymal stem cells from subcutaneous fat biopsies, and culture methods were developed to differentiate these into the adipogenic lineage. Biopsies were taken from 8 captive male (N = 6) and female (N = 2) brown bears, ages 2-12 years. Plastic adherent, fibroblast-like cells were proliferated and subsequently cryopreserved or differentiated. Differentiation conditions were optimized with respect to fetal bovine serum content and time spent in differentiation medium. Cultures were characterized through immunostaining, RT qPCR, and Oil red O staining to quantify lipid accumulation. Adiponectin, leptin, and glycerol medium concentrations were also determined over the course of differentiation. The culturing protocol succeeded in generating hormone-sensitive lipase-expressing, lipid-producing white-type adipocytes (UCP1 negative). Serum concentration and time of exposure to differentiation medium were both positively related to lipid production. Cells cultured to low passage numbers retained similar lipid production and expression of lipid markers PLIN2 and FABP4. Ultimately, the protocols described here may be useful to biologists in the field investigating the health of wild bear populations and could potentially increase our understanding of metabolic disorders in humans. PMID- 26856589 TI - Electrostatic engineering of the interface between heavy and light chains promotes antibody Fab fragment production. AB - Monoclonal antibodies and antibody fragments are used for diverse diagnostic and therapeutic applications. We have investigated the secretory production of Fab fragments from insect cells cotransfected with plasmid vectors carrying heavy- and light-chain genes. In the present study, to promote the formation of the disulfide bond between the heavy and light chains, some positively charged amino acid residues were introduced near the cysteine residue for the disulfide bond at the C-terminus of CL, while some negatively charged amino acid residues were added near the cysteine residue for the disulfide bond at the C-terminus of CH1. This electrostatic steering led to an increase in Fab secretions from insect cells. PMID- 26856590 TI - Evaluation of electroporation-induced adverse effects on adipose-derived stem cell exosomes. AB - In the recent years, the possibility of utilizing extracellular vesicles for drug delivery purposes has been investigated in various models, suggesting that these vesicles may have such potential. In addition to the choice of donor cell type for vesicle production, a major obstacle still exists with respect of loading the extracellular vesicles efficiently with the drug of choice. One of the proposed solutions to this problem has been drug loading by electroporation, where small pores are created in the membrane of the extracellular vesicles, hereby allowing for free diffusion of the drug compound into the interior of the vesicle. We investigated the utility of adipose-derived stem cells (ASCs) as an efficient exosome donor cell type with a particular focus on the treatment of glioblastoma multiforme (GBM). In addition, we evaluated electroporation-induced effects on the ASC exosomes with respect to their endogenous potential of stimulating GBM proliferation, and morphological changes to single and multiple ASC exosomes. We found that electroporation does not change the endogenous stimulatory capacity of ASC exosomes on GBM cell proliferation, but mediates adverse morphological changes including aggregation of the exosomes. In order to address this issue, we have successfully optimized the use of a trehalose-containing buffer system as a way of maintaining the structural integrity of the exosomes. PMID- 26856591 TI - Pancreatojejunostomy with modified purse-string suture technique. AB - PURPOSE: Despite many efforts, pancreatic fistula remains the most troublesome complication following pancreatic resections, especially in case of anastomosis made with soft pancreatic tissue. The purpose of the authors was to show their modification of purse-string pancreatodigestive anastomosis and the results obtained. METHODS: Between January 2013 and June 2015, the technique was applied in 49 patients; one purse-string suture and two U-shaped mattress sutures were used to create the pancreatojejunal anastomosis. In case of soft pancreatic parenchyma, an external stent was temporarily left in the main pancreatic duct. The most frequent pathology was pancreatic cancer, and a pylorus-preserving Whipple procedure was mostly done. RESULTS: Postoperative early morbidity rate was 35 %. There were two fistulas, one grade A fistula from a fibrotic pancreas (4.2 %) and one grade B in case of a soft pancreas (4 %). However, there was no reoperation and mortality. CONCLUSIONS: According to favorable results, the modification of the purse-string suture technique makes this method even safer. PMID- 26856592 TI - Effects of carbon source and light intensity on the growth and total lipid production of three microalgae under different culture conditions. AB - We attempted to enhance the growth and total lipid production of three microalgal species, Isochrysis galbana LB987, Nannochloropsis oculata CCAP849/1, and Dunaliella salina, which are capable of accumulating high content of lipid in cells. Low nitrogen concentration under photoautotrophic conditions stimulated total lipid production, but a decreasing total lipid content and an increasing biomass were observed with increasing nitrogen concentration. Among the different carbon sources tested for heterotrophic cultivation, glucose improved the growth of all three strains. The optimal glucose concentration for growth of I. galbana LB987 and N. oculata CCAP849/1 was 0.02 M, and that of D. salina was 0.05 M. Enhanced growth occurred when they were cultivated under heterotrophic or mixotrophic conditions compared with photoautotrophic conditions. Meanwhile, high total lipid accumulation in cells occurred when they were cultivated under photoautotrophic or mixotrophic conditions. During mixotrophic cultivation, biomass production was not affected significantly by light intensity; however, both chlorophyll concentration and total lipid content increased dramatically with increasing light intensity up to 150 umol/m(2)/s. The amount and composition ratio of saturated and unsaturated fatty acids in cells were different from each other depending on both species and light intensity. The highest accumulation of total fatty acid (C16-C18) among the three strains was found from cells of N. oculata CCAP849/1, which indicates that this species can be used as a source for production of biodiesel. PMID- 26856593 TI - Enhancing post anaerobic digestion of full-scale anaerobically digested sludge using free nitrous acid treatment. AB - In some wastewater treatment plants (WWTPs), the ever increasing production of sludge with the expanding population overloaded the anaerobic digestion which compromises the sludge reduction efficiency. Post anaerobic digestion of anaerobically digested sludge (ADS) has been applied to enhance sludge reduction, however, to a very limited extent. This study verified the effectiveness of free nitrous acid (FNA i.e. HNO2) pre-treatment on enhancing full-scale ADS degradation in post anaerobic digestion. The ADS collected from a full-scale WWTP was subject to FNA treatment at concentrations of 0.77, 1.54, 2.31, 3.08, and 3.85 mg N/L for 24 h followed by biochemical methane potential tests. The FNA treatment at all concentrations resulted in an increase (from 1.5-3.1 % compared to the control) in sludge reduction with the highest improvement achieved at 0.77 mg HNO2-N/L. The FNA treatment at this concentration also resulted in the highest increase in methane production (40 %) compared to the control. The economic analysis indicates that FNA treatment is economically attractive for enhancing post anaerobic digestion of full-scale ADS. PMID- 26856594 TI - Skin Examination Practices Among Melanoma Survivors and Their Children. AB - Many professional organizations recommend skin self-examination (SSE) as a tool for early detection of malignancy among melanoma survivors, a growing population that is at increased risk for new or recurrent melanoma. This study examined the frequency and correlates of SSE use among melanoma survivors. Additionally, we assessed skin exam use among children of survivors, who are at elevated lifetime risk for the disease. The California Cancer Registry was used to identify melanoma survivors, who were contacted, screened for eligibility, and invited to participate in a survey. The survey, administered by mail, web, or telephone, assessed a broad range of topics related to melanoma prevention in high-risk families. The present study focuses on skin examination practices of survivors and their children and potential correlates of these practices. Among a sample of 316 melanoma survivors, fewer than one in five participants performed monthly skin self-exams, a lower rate than that observed in previous studies. Although greater family history of melanoma, use of skin protection strategies, and the perceived severity of melanom were associated with more frequent use of skin self exams, these relationships disappeared in adjusted analyses. Participants reported unexpectedly frequent use of skin examinations for their children despite the lack of professional guidelines for this practice. Interventions are needed to improve skin self-examination practices among melanoma survivors and to counsel parents about optimal melanoma prevention strategies for their children. PMID- 26856595 TI - A cohesin-based structural platform supporting homologous chromosome pairing in meiosis. AB - The pairing and recombination of homologous chromosomes during the meiotic prophase is necessary for the accurate segregation of chromosomes in meiosis. However, the mechanism by which homologous chromosomes achieve this pairing has remained an open question. Meiotic cohesins have been shown to affect chromatin compaction; however, the impact of meiotic cohesins on homologous pairing and the fine structures of cohesion-based chromatin remain to be determined. A recent report using live-cell imaging and super-resolution microscopy demonstrated that the lack of meiotic cohesins alters the chromosome axis structures and impairs the pairing of homologous chromosomes. These results suggest that meiotic cohesin based chromosome axis structures are crucial for the pairing of homologous chromosomes. PMID- 26856587 TI - The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. AB - Lifestyle choices influence 20-40 % of adult peak bone mass. Therefore, optimization of lifestyle factors known to influence peak bone mass and strength is an important strategy aimed at reducing risk of osteoporosis or low bone mass later in life. The National Osteoporosis Foundation has issued this scientific statement to provide evidence-based guidance and a national implementation strategy for the purpose of helping individuals achieve maximal peak bone mass early in life. In this scientific statement, we (1) report the results of an evidence-based review of the literature since 2000 on factors that influence achieving the full genetic potential for skeletal mass; (2) recommend lifestyle choices that promote maximal bone health throughout the lifespan; (3) outline a research agenda to address current gaps; and (4) identify implementation strategies. We conducted a systematic review of the role of individual nutrients, food patterns, special issues, contraceptives, and physical activity on bone mass and strength development in youth. An evidence grading system was applied to describe the strength of available evidence on these individual modifiable lifestyle factors that may (or may not) influence the development of peak bone mass (Table 1). A summary of the grades for each of these factors is given below. We describe the underpinning biology of these relationships as well as other factors for which a systematic review approach was not possible. Articles published since 2000, all of which followed the report by Heaney et al. [1] published in that year, were considered for this scientific statement. This current review is a systematic update of the previous review conducted by the National Osteoporosis Foundation [1]. [Table: see text] Considering the evidence based literature review, we recommend lifestyle choices that promote maximal bone health from childhood through young to late adolescence and outline a research agenda to address current gaps in knowledge. The best evidence (grade A) is available for positive effects of calcium intake and physical activity, especially during the late childhood and peripubertal years-a critical period for bone accretion. Good evidence is also available for a role of vitamin D and dairy consumption and a detriment of DMPA injections. However, more rigorous trial data on many other lifestyle choices are needed and this need is outlined in our research agenda. Implementation strategies for lifestyle modifications to promote development of peak bone mass and strength within one's genetic potential require a multisectored (i.e., family, schools, healthcare systems) approach. PMID- 26856596 TI - Successful subcarinal dissection using a laparoscopic transhiatal approach for esophageal cancer with an anomalous pulmonary vein. AB - We herein reported a case of a dangerous anomaly of a pulmonary vein in subcarinal dissection. A 74-year-old man underwent esophagectomy with systematic nodal dissection using a laparoscopic transhiatal approach. Under pneumomediastinum pressure, dissection of the posterior plane of the pericardium was extended, and a vessel that independently drained into the left atrium was identified. Although this anomalous vein penetrated the subcarinal lymph nodes and crossed behind the right main bronchi, subcarinal dissection was successfully performed without its injury. Our surgical procedure enabled the intraoperative identification of this rare abnormality, an aberrant segmental vein in the right upper lobe, and safe en bloc subcarinal dissection. PMID- 26856597 TI - Preoperative low-dose weekly cisplatin and continuous infusion fluorouracil plus hyperfractionated radiotherapy in stage II-III esophageal carcinoma. AB - BACKGROUND: The optimal regimen of preoperative chemoradiotherapy for resectable esophageal cancer has not been established. We evaluated accelerated hyperfractionated radiotherapy (RT) concurrent to low-dose weekly cisplatin and continuous infusion fluorouracil (LDCI-FU) followed by esophagectomy in patients with locally advanced squamous cell carcinoma (SCC) of the esophagus. METHODS: Patients with clinical stage II or III SCC of the esophagus received cisplatin 30 mg/m2/week (days 1, 8, 15), LDCI-FU 300 mg/m2/day (days 1-21), and concomitant RT to a dose of 45 Gy (150 cGy/fraction, 2 fractions/day) on tumor and affected lymph nodes, followed by radical esophagectomy. RESULTS: From 1997 to 2012, 64 patients were treated with this regimen. Twenty-four patients (37 %) had grade 3 esophagitis, 18 (28 %) of whom required hospitalization. The risk of hospitalization was reduced by placement of a jejunostomy tube before starting induction chemoradiotherapy. Six patients (9 %) had grade 3-4 neutropenia. Fifty three patients (83 %) underwent esophageal resection and complete resection was achieved in 45 (70 %). The overall median survival was 28 months (95 % CI: 20.4 35.6) and 5-year survival was 38 %. In the 18 patients attaining a pathological complete response, median survival was 132 months and 5-year survival was 72 %. Positron emission tomography standardized uptake values (PET SUVmax) post chemoradiotherapy were associated with pathological response (p = 0.03) and survival (p = 0.04). CONCLUSIONS: Intensive preoperative hyperfractionated RT concomitant to low-dose cisplatin and LDCI-FU is effective in patients with locally advanced SCC of the esophagus, with good pathological response and survival and manageable toxicities. Post-chemoradiotherapy PET SUVmax shows promise as a potential prognostic factor. PMID- 26856598 TI - Regulation of epithelial-mesenchymal transition in endometrial cancer: connecting PI3K, estrogen signaling, and microRNAs. AB - Endometrial cancer (EC) prognosis is dependent on many factors such as time of diagnosis, histological type, and degree of invasion. Type I EC has a more favorable prognosis as it is less prone to myometrial invasion, which is believed to be the first step in the metastatic cascade. Type II EC displays a more aggressive and motile phenotype, and therefore has a poorer prognosis. Recent work suggests that despite the epithelial nature of Type I and Type II endometrial tumors, both are capable of undergoing an epithelial-mesenchymal transition (EMT), which may facilitate myometrial invasion and metastasis. Activation of the PI3K/Akt pathway has been shown to contribute to EMT through the upregulation of EMT-associated factors. Recent research has also linked estrogen signaling and microRNAs to the regulatory mechanisms that drive EMT in EC. Understanding the intricate relationships between these pathways will provide a better understanding of metastatic progression in EC. PMID- 26856599 TI - Role of taxanes in advanced prostate cancer. AB - Advanced prostate cancer is an androgen-dependent disease for which the initial treatment is an androgen deprivation maneuver. However, some primary resistances to hormonal treatment occur with increasing incidence throughout the evolution of the disease. The taxanes, docetaxel and cabazitaxel, exert their action at multiple levels at the tumor cell: besides inhibiting the mitosis and inducing the cell death, they induce the nuclear accumulation of FOXO1, a potent nuclear factor that acts against the activation of androgen receptor inhibiting the transcription of AR-V7 variant associated with the development of resistances to abiraterone and enzalutamide. Docetaxel, as first-line therapy, and cabazitaxel, as second-line therapy, have demonstrated to increase the survival in castration resistant prostate cancer. The results from last studies either on high-risk localized disease or on androgen-sensitive tumors demonstrate the increasing role of taxanes at earlier states of prostate cancer. PMID- 26856600 TI - Consensus and controversies in the definition, assessment, treatment and monitoring of BTcP: results of a Delphi study. AB - INTRODUCTION: There is no unanimous consensus on the clinical features to define breakthrough cancer pain (BTcP). The current project aimed to investigate the opinion of a panel of experts on cancer pain on how to define, diagnose, assess, treat and monitor BTcP. MATERIALS AND METHODS: A two-round Spanish multi-centre exploratory Delphi study was conducted with medical experts (n = 90) previously selected from Medical Oncology Services, Radiation Oncology, Palliative Care/Home Care Teams, and Pain Units. The study intended to seek experts' consensus and to define a set of recommendations for the management of BTcP. RESULTS: It was generally agreed that, definition of BTcP implies that baseline pain should be controlled (84 %), although not necessarily with opioids (only 30 %); there must be exacerbations (98.9 %); the duration of each episode should last <1 h (70 %); the intensity of pain >=7 out of 10 (67.8 %); and the number of flares per day should not be less than four. All participants supported the use of the Davies algorithm for the diagnosis. The use of a 'Patient Diary' was highly recommended. The optimal treatment should have a rapid onset, a short-acting analgesic effect (1-2 h) and transmucosal nasal or oral administration. It was considered very important to develop protocols for the management of cancer pain. CONCLUSIONS: The present Delphi study identified a set of recommendations to define, assess and monitor BTcP. PMID- 26856601 TI - PL Properties of Sr2CeO4 With Eu(3+) and Dy(3+) for Solid State Lighting Prepared by Precipitation Method. AB - Photoluminescence studies of pure and Dy(3+), Eu(3+) doped Sr2CeO4 compounds are presented by oxalate precipitation method for solid state lighting. The prepared samples also characterized by XRD, SEM (EDS) and FTIR spectroscopy. The pure Sr2CeO4 compound displays a broad band in its emission spectrum when excited with 280 nm wavelength, which peaks centered at 488 nm, which is due to the energy transfer between the molecular orbital of the ligand and charge transfer state of the Ce(4+) ions. Emission spectra of Sr2CeO4 with different concentration of Dy(3+) ions under near UV radiation excitation, shows that intensity of luminescence spectra is found to be affected by Dy(3+) ions, and it increases with adding some percentages of Dy(3+) ions. The maximum doping concentration for quenching is found to be Dy(3+) = 0.2 mol % to Sr(2+)ions. The observed broad spectrum from 400 to 560 nm is mainly due to CT transitions in Sr2CeO4 matrix and some fractional contribution of transitions between (4)F9/2 -> (6)H15/2 of Dy(3+) ions. Secondly the effect of Eu(3+) doping at the Sr(2+) site in Sr2CeO4, have been studied. The results obtained by doping Eu(3+) concentrations (0.2 mol% to 1.5 mol%), the observed excitation and emission spectra reveal excellent energy transfer between Ce(4+) and Eu(3+). The phenomena of concentration quenching are explained on the basis of electron phonon coupling and multipolar interaction. This energy transfer generates white light with a color tuning from blue to red, the tuning being dependent on the Eu(3+) concentration. The results establish that the compound Sr2CeO4 with Eu(3+) = 1 mol% is an efficient "single host lattice" for the generation of white lights under near UV-LED and blue LED irradiation. The commission internationale de I'Eclairage (CIE) coordinates were calculated by Spectrophotometric method using the spectral energy distribution of prepared phosphors. PMID- 26856604 TI - Hydrolysis of Cellulose by a Mesoporous Carbon-Fe2(SO4)3/gamma-Fe2O3 Nanoparticle Based Solid Acid Catalyst. AB - Carbon-based solid acid catalysts have shown significant potential in a wide range of applications, and they have been successfully synthesized using simple processes. Magnetically separable mesoporous carbon composites also have enormous potential, especially in separation and adsorption technology. However, existing techniques have been unable to produce a magnetically separable mesoporous solid acid catalyst because no suitable precursors have been identified. Herein we describe a magnetically separable, mesoporous solid acid catalyst synthesized from a newly developed mesoporous carbon-gamma-Fe2O3 nanoparticle composite. This material exhibits an equivalent acid density and catalytic activity in the hydrolysis of microcrystalline cellulose, to that of the cellulose-derived conventional catalyst. Since it is magnetically separable, this material can be readily recovered and reused, potentially reducing the environmental impact of industrial processes to which it is applied. PMID- 26856605 TI - Functional Uncoupling NMDAR NR2A Subunit from PSD-95 in the Prefrontal Cortex: Effects on Behavioral Dysfunction and Parvalbumin Loss after Early-Life Stress. PMID- 26856603 TI - Primate-specific miR-603 is implicated in the risk and pathogenesis of Alzheimer's disease. AB - Alzheimer's disease (AD) is a serious neurodegenerative disease, and microRNAs (miRNAs) have been linked to its pathogenesis. miR-603, a novel primate-specific miRNA and an intronic miRNA of a human brain highly expressed gene KIAA1217, is implicated in the risk and pathogenesis of AD. The rs11014002 single nucleotide polymorphism (SNP) (C/U), which locates in miR-603 precursor (pre-miR-603), exhibits a protective effect towards AD risk. Additionally, the rs11014002 SNP promotes the biogenesis of mature miR-603. miR-603 downregulates LRPAP1 mRNA and protein levels through directly binding the 3' untranslated region (3'UTR) of LRPAP1. Moreover, miR-603 increases LRP1 protein expression. LRPAP1 and LRP1, playing opposite roles, are involved in Abeta clearance and pathogenesis of AD. Strikingly, miR-603 exhibits a relatively higher expression and there is a loss of a negative correlation between miR-603 and LRPAP1/RND1 mRNA levels in the hippocampi of patients with AD. In addition, miR-603 directly downregulates a key neuronal apoptotic component-E2F1, and prevents HeLa cells from undergoing H2O2 induced apoptosis. This work suggests that miR-603 may be a novel AD-relevant miRNA and that its rs11014002 SNP may serve as a protective factor against AD. PMID- 26856607 TI - A change of gear at MUN. PMID- 26856606 TI - Sequestration of nanoparticles by an EPS matrix reduces the particle-specific bactericidal activity. AB - Most artificial nanomaterials are known to exhibit broad-spectrum bactericidal activity; however, the defence mechanisms that bacteria use based on extracellular polymeric substances (EPS) to detoxify nanoparticles (NPs) are not well known. We ruled out the possibility of ion-specific bactericidal activity by showing the lack of equivalent dissolved zinc and silicon toxicity and determined the particle-specific toxicity of ZnO and SiO2 nanoparticles (ZnONPs/SiO2NPs) through dialysis isolation experiments. Surprisingly, the manipulation of the E. coli EPS (i.e., no EPS manipulation or EPS removal by sonication/centrifugation) showed that their particle-specific bactericidal activity could be antagonized by NP-EPS sequestration. The survival rates of pristine E. coli (no EPS manipulation) reached 65% (ZnONPs, 500 mg L(-1)) and 79% (SiO2NPs, 500 mg L(-1)), whereas survival rates following EPS removal by sonication/centrifugation were 11% and 63%, respectively. Transmission electron microscopy (TEM) combined with fluorescence micro-titration analysis and Fourier-transform infrared spectroscopy (FTIR) showed that protein-like substances (N-H and C-N in amide II) and secondary carbonyl groups (C=O) in the carboxylic acids of EPS acted as important binding sites that were involved in NP sequestration. Accordingly, the amount and composition of EPS produced by bacteria have important implications for the bactericidal efficacy and potential environmental effects of NPs. PMID- 26856608 TI - Comparison of creatinine clearance estimates in subgroups based on Body Mass Index and albumin. AB - BACKGROUND: The establishment of accurate equations for glomerular filtration rate (GFR) estimations is still far from the realization. Factors such as age, diabetes, stage of CKD, pregnancy, muscle mass and ethic nation are associated with less reliance upon commonly utilized estimation equations. We aimed to compare the routine use of 24-hour creatinine clearance (CrCl) and GFR estimates calculated by Crockoft-Gault (CG) and modification of diet in renal disease (MDRD) formulas in patients with different levels of renal dysfunction in subgroups, based on Body Mass Index (BMI) and serum albumin (Alb) levels. METHODS: Two hundred and seventy-nine non diabetic patients (172 men and 107 women), aged 54+/-23 years, with BMI 27.3+/-4.4 were enrolled in the study. All patients presented creatinine 1.8+/-1.2 (mg/dL) and Alb 3.5+/-1.3g/dL. The comparison of CrCl versus CG had bias 3.1 while the comparison of CrCl versus MDRD had a bias of 6.6. RESULTS: Univariate analysis showed that age, sex and BMI were not significant biases related to the CG, MDRD and CrCl. Indeed, the bias related to the CG was significantly lower than that related to MDRD in patients with either low or high serum albumin. Interestingly, the bias associated with CG was 1.3 in non-diabetic patients with Alb <=3.5 mg /dL suggesting that CG equation could be used interchangeable to CrCl in these patients. CONCLUSION: CG gave a better prediction of measured CrCl than MDRD in Mediterranean, non diabetic, non-hospitalized patients although misclassification of patients with regard to renal impairment stage was not present. PMID- 26856609 TI - Factors influencing first vascular access placement in patients starting hemodialysis. AB - BACKGROUND: The aim of the study was to assess whether age, gender and the primary renal disease are associated with differences in the type of first vascular access placement. METHODS: We reviewed the records of 145 patients on hemodialysis (HD) 44 females and 101 males with a mean age of 64+/-14.5 years, on HD for 46.9+/-41.2 months (range 1-252). RESULTS: The primary renal diseases were diabetes (23.4%), hypertension (17.2%), glomerulonephritis (25.7%), cardiac failure (6.9%) and others (26.8%). Double lumen catheter and arteriovenous fistula was the first vascular access in 109 (75%) and 35 patients (24%) patients, respectively. Graft was the first vascular access in 1 patient (0.5%). Arteriovenous fistula was the first choice for 29.7% of the male patients and 9% of the female. Double lumen catheter was the first choice for 70.3% of the male (subclavian 50.5%, femoral 4.95%, and jugular 14.85%) and 86.4% of the female (subclavian 75%, femoral 2.3%, and jugular 9.1%) (P=0.04). Double lumen catheter was the first choice for 79.7% of the patients older than 65 years and 70.4% for the patients younger than 65 years (P=0.19). Double lumen catheter was the first choice for all the patients with cardiac failure as the primary cause of renal disease. CONCLUSION: Double lumen catheter was the first vascular access for the majority of our patients, probably due to late Nephrologist's referral. Cardiac failure being the primary cause of renal disease and female gender influence also this choice, but not the age of the patients. PMID- 26856610 TI - Live or let die: when intermittent peritoneal dialysis is the only plausible solution for survival. PMID- 26856611 TI - Acute kidney injury. PMID- 26856613 TI - Implementation of an Automated High-Throughput Plasmid DNA Production Pipeline. AB - Biologics sample management facilities are often responsible for a diversity of large-molecule reagent types, such as DNA, RNAi, and protein libraries. Historically, the management of large molecules was dispersed into multiple laboratories. As methodologies to support pathway discovery, antibody discovery, and protein production have become high throughput, the implementation of automation and centralized inventory management tools has become important. To this end, to improve sample tracking, throughput, and accuracy, we have implemented a module-based automation system integrated into inventory management software using multiple platforms (Hamilton, Hudson, Dynamic Devices, and Brooks). Here we describe the implementation of these systems with a focus on high-throughput plasmid DNA production management. PMID- 26856612 TI - Clinical and Immunological Features of Opsoclonus-Myoclonus Syndrome in the Era of Neuronal Cell Surface Antibodies. AB - IMPORTANCE: Most studies on opsoclonus-myoclonus syndrome (OMS) in adults are based on small case series before the era of neuronal cell surface antibody discovery. OBJECTIVE: To report the clinical and immunological features of idiopathic OMS (I-OMS) and paraneoplastic OMS (P-OMS), the occurrence of antibodies to cell surface antigens, and the discovery of a novel cell surface epitope. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study and laboratory investigations of 114 adult patients with OMS at a center for autoimmune neurological disorders done between January 2013 and September 2015. MAIN OUTCOMES AND MEASURES: Review of clinical records. Immunohistochemistry on rat brain and cultured neurons as well as cell-based assays were used to identify known autoantibodies. Immunoprecipitation and mass spectrometry were used to characterize novel antigens. RESULTS: Of the 114 patients (62 [54%] female; median age, 45 years; interquartile range, 32-60 years), 45 (39%) had P-OMS and 69 (61%) had I-OMS. In patients with P-OMS, the associated tumors included lung cancer (n = 19), breast cancer (n = 10), other cancers (n = 5), and ovarian teratoma (n = 8); 3 additional patients without detectable cancer were considered to have P-OMS because they had positive results for onconeuronal antibodies. Patients with I-OMS, compared with those who had P-OMS, were younger (median age, 38 [interquartile range, 31-50] vs 54 [interquartile range, 45-65] years; P < .001), presented more often with prodromal symptoms or active infection (33% vs 13%; P = .02), less frequently had encephalopathy (10% vs 29%; P = .01), and had better outcome (defined by a modified Rankin Scale score <= 2 at last visit; 84% vs 39%; P < .001) with fewer relapses (7% vs 24%; P= .04). Onconeuronal antibodies occurred in 13 patients (11%), mostly Ri/ANNA2 antibodies, which were detected in 7 of 10 patients (70%) with breast cancer. Neuronal surface antibodies were identified in 12 patients (11%), mainly glycine receptor antibodies (9 cases), which predominated in P-OMS with lung cancer (21% vs 5% in patients with OMS without lung cancer; P = .02); however, a similar frequency of glycine receptor antibodies was found in patients with lung cancer without OMS (13 of 65 patients [20%]). A novel cell surface epitope, human natural killer 1 (HNK-1), was the target of the antibodies in 3 patients with lung cancer and P OMS. CONCLUSIONS AND RELEVANCE: Patients with I-OMS responded better to treatment and had fewer relapses than those with P-OMS. Older age and encephalopathy, significantly associated with P-OMS, are clinical clues suggesting an underlying tumor. Glycine receptor antibodies occur frequently in P-OMS with lung cancer, but the sensitivity and specificity are low. The HNK-1 epitope is a novel epitope in a subset of patients with P-OMS and lung cancer. PMID- 26856615 TI - A SHOCKING REQUIREMENT IN THE LAW ON NEGLIGENCE LIABILITY FOR PSYCHIATRIC ILLNESS: LIVERPOOL WOMEN'S HOSPITAL NHS FOUNDATION TRUST V RONAYNE [2015] EWCA CIV 588. AB - The Ronayne case concerned a husband who suffered a psychiatric illness, described as an adjustment disorder, in seeing the condition of his wife who was the primary victim of admitted medical negligence. His claim for compensation, as a 'secondary victim', failed because he could not satisfy the legal requirement that there must be a sudden shocking event. This commentary criticises that requirement which appears to make no medical sense. PMID- 26856614 TI - The importance of continued engagement during the implementation phase of tobacco control policies in a middle-income country: the case of Costa Rica. AB - OBJECTIVE: To analyse the process of implementing and enforcing smoke-free environments, tobacco advertising, tobacco taxes and health warning labels from Costa Rica's 2012 tobacco control law. METHOD: Review of tobacco control legislation, newspaper articles and interviewing key informants. RESULTS: Despite overcoming decades of tobacco industry dominance to win enactment of a strong tobacco control law in March 2012 consistent with WHO's Framework Convention on Tobacco Control, the tobacco industry and their allies lobbied executive branch authorities for exemptions in smoke-free environments to create public confusion, and continued to report in the media that increasing cigarette taxes led to a rise in illicit trade. In response, tobacco control advocates, with technical support from international health groups, helped strengthen tobacco advertising regulations by prohibiting advertising at the point-of-sale (POS) and banning corporate social responsibility campaigns. The Health Ministry used increased tobacco taxes earmarked for tobacco control to help effectively promote and enforce the law, resulting in high compliance for smoke-free environments, advertising restrictions and health warning label (HWL) regulations. Despite this success, government trade concerns allowed, as of December 2015, POS tobacco advertising, and delayed the release of HWL regulations for 15 months. CONCLUSIONS: The implementation phase continues to be a site of intensive tobacco industry political activity in low and middle-income countries. International support and earmarked tobacco taxes provide important technical and financial assistance to implement tobacco control policies, but more legal expertise is needed to overcome government trade concerns and avoid unnecessary delays in implementation. PMID- 26856616 TI - French drug trial had three major failings, says initial report. PMID- 26856617 TI - Quality gaps identified through mortality review. AB - BACKGROUND: Hospital mortality rate is a common measure of healthcare quality. Morbidity and mortality meetings are common but there are few reports of hospital wide mortality-review processes to provide understanding of quality-of-care problems associated with patient deaths. OBJECTIVE: To describe the implementation and results from an institution-wide mortality-review process. DESIGN: A nurse and a physician independently reviewed every death that occurred at our multisite teaching institution over a 3-month period. Deaths judged by either reviewer to be unanticipated or to have any opportunity for improvement were reviewed by a multidisciplinary committee. We report characteristics of patients with unanticipated death or opportunity for improved care and summarise the opportunities for improved care. RESULTS: Over a 3-month period, we reviewed all 427 deaths in our hospital in detail; 33 deaths (7.7%) were deemed unanticipated and 100 (23.4%) were deemed to be associated with an opportunity for improvement. We identified 97 opportunities to improve care. The most common gap in care was: 'goals of care not discussed or the discussion was inadequate' (n=25 (25.8%)) and 'delay or failure to achieve a timely diagnosis' (n=8 (8.3%)). Patients who had opportunities for improvement had longer length of stay and a lower baseline predicted risk of death in hospital. Nurse and physician reviewers spent approximately 142 h reviewing cases outside of committee meetings. CONCLUSIONS: Our institution-wide mortality review found many quality gaps among decedents, in particular inadequate discussion of goals of care. PMID- 26856618 TI - A randomized, double blinded, placebo controlled trial of oral dydrogesterone supplementation in the management of preterm labor. AB - The primary aim of this study was to evaluate the effect of oral dydrogesterone on the recurrent uterine contraction in preterm labor. The secondary aims were to evaluate latency period, gestational age at delivery, pregnancy outcomes, neonatal outcomes, compliance and side effects. A randomized, double blinded, placebo controlled trial was conducted. Forty-eight pregnant women at 24-34 weeks gestation with preterm labor were either randomized to study group receiving tocolytic treatment combined with oral dydrogesterone (20 mg daily) or to placebo group receiving tocolytic treatment combined with oral placebo. Recurrent rates of uterine contraction were comparable between groups (87.5% vs 91.7%, p = 0.64). Latency periods were not different between dydrogesterone and placebo group (32.7 +/- 20.2 days vs 38.2 +/- 24.2 days, p = 0.39). There were also no differences in gestational age at delivery, pregnancy outcomes, neonatal outcomes, compliance and side effects. Adjuvant treatment with oral dydrogesterone 20 mg/day could not decrease the rates of recurrent uterine contraction and prolong latency period in preterm labor management when compared to placebo. PMID- 26856620 TI - Mechanical Symptoms and Arthroscopic Partial Meniscectomy in Patients With Degenerative Meniscus Tear: A Secondary Analysis of a Randomized Trial. AB - BACKGROUND: Recent evidence shows that arthroscopic partial meniscectomy (APM) offers no benefit over conservative treatment of patients with a degenerative meniscus tear. However, patients who report mechanical symptoms (sensations of knee catching or locking) may benefit from APM. OBJECTIVE: To assess whether APM improves mechanical symptoms better than sham surgery. DESIGN: Randomized, patient- and outcome assessor-blinded, sham surgery-controlled, multicenter trial. (ClinicalTrials.gov: NCT00549172). SETTING: 5 orthopedic clinics in Finland. PATIENTS: Adults (aged 35 to 65 years) with a degenerative medial meniscus tear and no knee osteoarthritis. INTERVENTION: APM or sham surgery. MEASUREMENTS: Patients' self-report of mechanical symptoms before surgery and at 2, 6, and 12 months after surgery. RESULTS: 70 patients were randomly assigned to APM, and 76 were assigned to sham surgery. Thirty-two patients (46%) in the APM group and 37 (49%) in the sham surgery group reported catching or locking before surgery; the corresponding numbers at any follow-up were 34 (49%) and 33 (43%), with a risk difference of 0.03 (95% CI, -0.06 to 0.12). In the subgroup of 69 patients with preoperative catching or locking, the risk difference was 0.07 (CI, -0.08 to 0.22). LIMITATION: Analyses were post hoc, and the results are only generalizable to knee catching and occasional locking because few patients reported other types of mechanical symptoms. CONCLUSION: Resection of a torn meniscus has no added benefit over sham surgery to relieve knee catching or occasional locking. These findings question whether mechanical symptoms are caused by a degenerative meniscus tear and prompt caution in using patients' self report of these symptoms as an indication for APM. PRIMARY FUNDING SOURCE: Academy of Finland. PMID- 26856619 TI - Cell type-specific properties and environment shape tissue specificity of cancer genes. AB - One of the biggest mysteries in cancer research remains why mutations in certain genes cause cancer only at specific sites in the human body. The poor correlation between the expression level of a cancer gene and the tissues in which it causes malignant transformations raises the question of which factors determine the tissue-specific effects of a mutation. Here, we explore why some cancer genes are associated only with few different cancer types (i.e., are specific), while others are found mutated in a large number of different types of cancer (i.e., are general). We do so by contrasting cellular functions of specific-cancer genes with those of general ones to identify properties that determine where in the body a gene mutation is causing malignant transformations. We identified different groups of cancer genes that did not behave as expected (i.e., DNA repair genes being tissue specific, immune response genes showing a bimodal specificity function or strong association of generally expressed genes to particular cancers). Analysis of these three groups demonstrates the importance of environmental impact for understanding why certain cancer genes are only involved in the development of some cancer types but are rarely found mutated in other types of cancer. PMID- 26856621 TI - Influence of conjugation and other structural changes on the activity of Cu2+ based PNAzymes. AB - We have previously shown that PNA-neocuproine conjugates can act as artificial RNA restriction enzymes. In the present study we have additionally conjugated the PNA with different entities, such as oligoethers, peptides etc. and also constructed systems where the PNA is designed to clamp the target RNA forming a triplex. Some conjugations are detrimental for the activity while most are silent which means that conjugation can be done to alter physical properties without losing activity. Conjugation with a single oligoether close to the neocuproine does enhance the rate almost twofold compared to the system without the oligoether. The systems designed to clamp the RNA target by forming a triplex retain the activity if the added oligoT sequence is 5 PNA units or shorter and extends the arsenal of artificial RNA restriction enzymes. Changing the direction of a closing base pair, where the target RNA forms a bulge, from a GC to a CG pair enhances the rate of cleavage somewhat without compromising the selectivity, leading to the so far most efficient artificial nuclease reported. PMID- 26856622 TI - Quantitative assessment of radiation force effect at the dielectric air-liquid interface. AB - We induce nanometer-scale surface deformation by exploiting momentum conservation of the interaction between laser light and dielectric liquids. The effect of radiation force at the air-liquid interface is quantitatively assessed for fluids with different density, viscosity and surface tension. The imparted pressure on the liquids by continuous or pulsed laser light excitation is fully described by the Helmholtz electromagnetic force density. PMID- 26856623 TI - Impact of protein-rich meals on glycaemic response of rice. AB - Asians typically consume carbohydrate-rich and high-glycaemic-index diets that have been associated with an increased risk of developing type 2 diabetes. Rice is rarely eaten alone such that it is of interest to investigate the effects of co-ingesting different protein-rich meals with rice on insulin and glycaemic response. This study had a randomised, controlled, non-blind, cross-over design in which fifteen healthy Chinese male participants were required to come on non consecutive days. Five rice-based test meals were served: rice alone (control), rice with fish (RWF), rice with egg white (RWE), rice with soya beancurd (taukwa) (RWT) and rice with chicken (RWC). The control meal consisted of 50 g of available carbohydrate, whereas all other test meals contained additional 25 g of protein. RWT was the only meal that showed significantly lower glucose response when compared with the control (P<0.05). RWF and RWE had significantly higher insulin response, but no significant increase was observed in RWT and RWC when compared with the control (P<0.05). RWT and RWF showed significantly higher glucagon secretion as compared with the control (P<0.05). The four test meals studied showed varying effects, with RWT showing the greatest reduction in glycaemic response. Therefore, the ingestion of soya beancurd with rice may have a direct impact on reducing the risk in Asians transiting from being pre diabetics to diabetics. PMID- 26856624 TI - Determination of Vitamin E and Vitamin A in Infant Formula and Adult Nutritionals by Normal-Phase High-Performance Liquid Chromatography: Collaborative Study, Final Action 2012.10. AB - The main objective of the AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) project is to establish international consensus methods for infant formula and adult nutritionals, which will benefit intermarket supply and dispute resolution. A collaborative study was conducted on AOAC First Action Method 2012.10 Simultaneous Determination of 13-cis and All-trans Vitamin A Palmitate (Retinyl Palmitate), Vitamin A Acetate (Retinyl Acetate), and Total Vitamin E (alpha-Tocopherol and D-alpha-tocopherol acetate) in Infant Formula and Adult Nutritionals by Normal-Phase HPLC. Fifteen laboratories from 11 countries participated in an interlaboratory study to determine 13-cis and all-trans vitamin A palmitate (retinyl palmitate), vitamin A acetate (retinyl acetate), and total vitamin E (alpha-tocopherol and D-alpha-tocopherol acetate) in infant formula and adult nutritionals by normal-phase HPLC and all laboratories returned valid data. Eighteen test portions of nine blind duplicates of a variety of infant formula and adult nutritional products were used in the study. The matrixes included milk-based and soy-based hydrolyzed protein as well as a low fat product. Each of the samples was prepared fresh and analyzed in singlicate. As the number of samples exceeded the recommended number to be prepared in a single day, analysis took place over 2 days running 12 samples on day one and 10 samples on day two. The reference standard stock was prepared once and the six point curve diluted freshly on each day. Results obtained from all 15 laboratories are reported. The RSDR for total vitamin A (palmitate or acetate) ranged from 6.51 to 22.61% and HorRat values ranged from 0.33 to 1.25. The RSDR for total vitamin E (as tocopherol equivalents) ranged from 3.84 to 10.78% and HorRat values ranged from 0.27 to 1.04. Except for an adult low fat matrix which generated reproducibility RSD >40% for some isomers, most SPIFAN matrixes gave results within the acceptance criteria of <16% RSD as stated in the respective Standard Method Performance Requirements. PMID- 26856625 TI - L'echographie equivaut-elle a la tomodensitometrie dans la prise en charge des patients avec suspicion d'urolithiase se presentant a l'urgence? AB - ARTICLE CHOSEN: Smith-Bindman R, Aubin C, Bailitz J., et al. Ultrasonography versus Computed Tomography for Suspected Nephrolithiasis. New Engl J Med 2014;371;1100-10. PMID- 26856626 TI - Telemedicine for Diabetes: Economic Considerations. PMID- 26856627 TI - Longer Usage Time for CSII Catheters: An Underestimated Challenge. PMID- 26856628 TI - Human Frataxin Folds Via an Intermediate State. Role of the C-Terminal Region. AB - The aim of this study is to investigate the folding reaction of human frataxin, whose deficiency causes the neurodegenerative disease Friedreich's Ataxia (FRDA). The characterization of different conformational states would provide knowledge about how frataxin can be stabilized without altering its functionality. Wild type human frataxin and a set of mutants, including two highly destabilized FRDA associated variants were studied by urea-induced folding/unfolding in a rapid mixing device and followed by circular dichroism. The analysis clearly indicates the existence of an intermediate state (I) in the folding route with significant secondary structure content but relatively low compactness, compared with the native ensemble. However, at high NaCl concentrations I-state gains substantial compaction, and the unfolding barrier is strongly affected, revealing the importance of electrostatics in the folding mechanism. The role of the C-terminal region (CTR), the key determinant of frataxin stability, was also studied. Simulations consistently with experiments revealed that this stretch is essentially unstructured, in the most compact transition state ensemble (TSE2). The complete truncation of the CTR drastically destabilizes the native state without altering TSE2. Results presented here shed light on the folding mechanism of frataxin, opening the possibility of mutating it to generate hyperstable variants without altering their folding kinetics. PMID- 26856630 TI - Notch Filtering of Intracardiac Recordings: Improving Quality or Masking Reality? PMID- 26856629 TI - Gender Disparities in Symptoms of Anxiety, Depression, and Quality of Life in Defibrillator Recipients. AB - BACKGROUND: Most patients cope well with an implantable cardioverter defibrillator (ICD), but psychological distress and ICD-related concerns have been reported in about 20% of ICD recipients. Many previous studies have not distinguished between genders. METHODS: In this nationwide study we compared quality of life, anxiety, and depression symptoms between the genders in ICD recipients, and determined predictors of each of these variables in men and women. All adult Swedish ICD recipients were invited by mail to participate and 2,771 patients (66 +/- 12 years) completed standardized measures of quality of life, symptoms of anxiety, and depression. Time since implantation ranged from 1 year to 23 years with a mean of 4.7 +/- 3.9. RESULTS: Women reported worse quality of life (mean index 0.790 vs 0.825) and higher prevalence of anxiety (20.5% vs 14.7%) than did men (P < 0.001 for both comparisons), while there were no differences in symptoms of depression (8.8% vs 8.2%). CONCLUSIONS: Most ICD recipients report a good quality of life, without emotional distress, but among the minority with distress, women fare worse than men. PMID- 26856631 TI - Low Incidence of Central Venous Catheter-Related Bloodstream Infections in Stem Cell Transplant Patients in Eastern India Despite High Community Burden of Multidrug-Resistant Pathogens. PMID- 26856633 TI - Fabrication technologies and sensing applications of graphene-based composite films: Advances and challenges. AB - Graphene (G)-based composite materials have been widely explored for the sensing applications ascribing to their atom-thick two-dimensional conjugated structures, high conductivity, large specific surface areas and controlled modification. With the enormous advantages of film structure, G-based composite films (GCFs), prepared by combining G with different functional nanomaterials (noble metals, metal compounds, carbon materials, polymer materials, etc.), show unique optical, mechanical, electrical, chemical, and catalytic properties. Therefore, great quantities of sensors with high sensitivity, selectivity, and stability have been created in recent years. In this review, we focus on the recent advances in the fabrication technologies of GCFs and their specific sensing applications. In addition, the relationship between the properties of GCFs and sensing performance is concentrated on. Finally, the personal perspectives and key challenges of GCFs are mentioned in the hope to shed a light on their potential future research directions. PMID- 26856632 TI - A phase-contrast microscopy-based method for modeling the mechanical behavior of mesenchymal stem cells. AB - We present three-dimensional (3D) finite element (FE) models of single, mesenchymal stem cells (MSCs), generated from images obtained by optical phase contrast microscopy and used to quantify the structural responses of the studied cells to externally applied mechanical loads. Mechanical loading has been shown to affect cell morphology and structure, phenotype, motility and other biological functions. Cells experience mechanical loads naturally, yet under prolonged or sizable loading, damage and cell death may occur, which motivates research regarding the structural behavior of loaded cells. For example, near the weight bearing boney prominences of the buttocks of immobile persons, tissues may become highly loaded, eventually leading to massive cell death that manifests as pressure ulcers. Cell-specific computational models have previously been developed by our group, allowing simulations of cell deformations under compressive or stretching loads. These models were obtained by reconstructing specific cell structures from series of 2D fluorescence, confocal image-slices, requiring cell-specific fluorescent-staining protocols and costly (confocal) microscopy equipment. Alternative modeling approaches represent cells simply as half-spheres or half-ellipsoids (i.e. idealized geometries), which neglects the curvature details of the cell surfaces associated with changes in concentrations of strains and stresses. Thus, we introduce here for the first time an optical image-based FE modeling, where loads are simulated on reconstructed 3D geometrical cell models from a single 2D, phase-contrast image. Our novel modeling method eliminates the need for confocal imaging and fluorescent staining preparations (both expensive), and makes cell-specific FE modeling affordable and accessible to the biomechanics community. We demonstrate the utility of this cost effective modeling method by performing simulations of compression of MSCs embedded in a gel. PMID- 26856634 TI - An electrochemiluminescence biosensor for endonuclease EcoRI detection. AB - Endonucleases cleavage of DNA plays an important role in biological and medicinal chemistry. This work was going to develop a reliable and sensitive electrochemiluminescent (ECL) biosensor for detecting endonucleases by using gold nanoparticles graphene composite (GNPs-graphene) as a signal amplifier. Firstly, the GNPs and graphene were simultaneously deposited on the glassy carbon electrode (GCE) by cyclic voltammetry. Then a stem DNA was anchored on the surface of GCE. And with a modifying DNA introduced into the electrode by DNA assembly, a strong ECL signal was obtained. After a DNA modified with ferrocene assembly to the stem DNA, the ECL signal had a sharp decrease due to the quench effect of ferrocene to and the biosensor comes into being a "off" state. With the effect of endonuclease, the ECL signal had a recovery because of the ferrocene being released and the biosensor formed a "on" state. Moreover, the recovery of ECL signal was related to the concentration of endonucleases. Combining specific defined DNA and endonuclease, this method has a potential to detect different endonucleases. In this work, we took the EcoRI as an example to identify the feasibility of ECL biosensor in applying in sensitive detection of endonucleases using a GNPs-graphene signal amplifier. Under optimal condition, the proposed biosensor obtained a low limit of detection (LOD) 5.6*10-5UmL-1. And the stability, selectivity and reproducibility of the biosensor also were researched. PMID- 26856635 TI - [Small animal image-guided radiotherapy: A new era for preclinical studies]. AB - Preclinical external beam radiotherapy irradiations used to be delivered with a static broad beam. To promote the transfer from animal to man, the preclinical treatment techniques dedicated to the animal have been optimized to be similar to those delivered to patients in clinical practice. In this context, preclinical irradiators have been developed. Due to the small sizes of the animals, and the irradiation beams, the scaling to the small animal dimensions involves specific problems. Reducing the size and energy of the irradiation beams require very high technical performance, especially for the mechanical stability of the irradiator and the spatial resolution of the imaging system. In addition, the determination of the reference absorbed dose rate must be conducted with a specific methodology and suitable detectors. To date, three systems are used for preclinical studies in France. The aim of this article is to present these new irradiators dedicated to small animals from a physicist point of view, including the commissioning and the quality control. PMID- 26856636 TI - From epidemiological transition to modern cardiovascular epidemiology: hypertension in the 21st century. PMID- 26856638 TI - Controlling Interfacial Reactions and Intermetallic Compound Growth at the Interface of a Lead-free Solder Joint with Layer-by-Layer Transferred Graphene. AB - The immoderate growth of intermetallic compounds (IMCs) formed at the interface of a solder metal and the substrate during soldering can degrade the mechanical properties and reliability of a solder joint in electronic packaging. Therefore, it is critical to control IMC growth at the solder joints between the solder and the substrate. In this study, we investigated the control of interfacial reactions and IMC growth by the layer-by-layer transfer of graphene during the reflow process at the interface between Sn-3.0Ag-0.5Cu (in wt %) lead-free solder and Cu. As the number of graphene layers transferred onto the surface of the Cu substrate increased, the thickness of the total IMC (Cu6Sn5 and Cu3Sn) layer decreased. After 10 repetitions of the reflow process for 50 s above 217 degrees C, the melting temperature of Sn-3.0Ag-0.5Cu, with a peak temperature of 250 degrees C, the increase in thickness of the total IMC layer at the interface with multiple layers of graphene was decreased by more than 20% compared to that at the interface of bare Cu without graphene. Furthermore, the average diameter of the Cu6Sn5 scallops at the interface with multiple layers of graphene was smaller than that at the interface without graphene. Despite 10 repetitions of the reflow process, the growth of Cu3Sn at the interface with multiple layers of graphene was suppressed by more than 20% compared with that at the interface without graphene. The multiple layers of graphene at the interface between the solder metal and the Cu substrate hindered the diffusion of Cu atoms from the Cu substrate and suppressed the reactions between Cu and Sn in the solder. Thus, the multiple layers of graphene transferred at the interface between dissimilar metals can control the interfacial reaction and IMC growth occurring at the joining interface. PMID- 26856637 TI - Testing the assumptions underlying fMRI adaptation using intracortical recordings in area MT. AB - We investigated how neural activity in the middle temporal area of the macaque monkey changes after 3 sec of exposure to a visual stimulus and used this to gain insight into the assumptions underlying the fMRI adaptation method (fMRIa). We studied both changes in tuning curves following weak and strong motion stimuli (adaptation) and the differences between a first and second exposure to the same stimulus (repetition suppression). Typically, tuning curves had smaller amplitudes and narrower tuning widths after strong adaptation; this was true for single neurons, multi-unit activity (MUA), the evoked local field potential (LFP), as well as gamma band activity. Repetition typically led to reduced responses. This reduction was correlated with direction selectivity and not explained by neural fatigue. Our data, however, warn against a simplistic view of the consequences of adaptation. First, a considerable fraction of neurons and sites showed response enhancements after adaptation, especially when probed with a stimulus that moved opposite to the direction of the adapting stimulus. Second, adaptation was stimulus selective only on a time scale of ~100 msec. Third, aggregate measures of neural activity (MUA, LFPs) had substantially different adaptation effects. Fourth, there were qualitative differences between our findings in MT and earlier findings in IT cortex. We conclude that selective adaptation effects in fMRIa are relatively easy to miss even when they exist (for instance by presenting stimuli for too long, or because neurons that enhance after adaptation cancel out the effect of neurons that suppress). Moreover, we argue that adaptation should be understood in the context of the computations that a neural circuit perform. Using fMRIa as a tool to uncover neural selectivity requires a better understanding of this circuitry and its consequences for adaptation. PMID- 26856639 TI - Storage duration of transfused red blood cells is not significantly associated with postoperative adverse events in pediatric cardiac surgery patients. AB - The aim of this study was to evaluate the association of storage duration of transfused red blood cells with the risk of postoperative serious adverse events in pediatric cardiac surgery patients. We studied 517 patients and found that 22 patients (4.3%) had at least one serious adverse event. The maximum and mean storage duration of transfused red blood cells did not differ significantly between patients with and without serious adverse events (maximum, p = 0.89; mean, p = 0.81). In our study of pediatric cardiac surgery patients, the storage duration of transfused red blood cells was not significantly associated with the risk of serious adverse events. PMID- 26856640 TI - Is arterial base deficit still a useful prognostic marker in trauma? A systematic review. AB - BACKGROUND: Arterial base deficit (BD) has been widely used in trauma patients since 1960. However, trauma management has also evolved significantly in the last 2 decades. The first objective of this study was to systematically review the literature on the relationship between arterial BD as a prognostic marker for trauma outcomes (mortality, significant injuries, and major complications) in the acute setting. The second objective was to evaluate arterial BD as a prognosis marker, specifically, in the elderly and in patients with positive blood alcohol levels. METHODS: MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews were searched from January 1, 1990, to August 6, 2015. Bibliographies of articles were also hand searched for relevant citations. RESULTS: Thirty-four studies were included in this review. The studies consistently showed that a higher arterial BD was associated with increased mortality, significant injuries, and major complications. The threshold BD value of 6 mmol/L was also useful in discriminating for poorer outcomes. The presence of alcohol did not affect the ability of arterial BD to discriminate between major and minor injuries. Elderly patients had higher mortality in all arterial BD categories compared to the younger age group. CONCLUSIONS: Despite the advances in trauma care in the last 2 decades, arterial BD remains a useful prognostic marker in trauma patients, even in elderly patients and in patients who had consumed alcohol. The threshold BD value of 6 mmol/L was useful to prognosticate poorer outcomes. PMID- 26856642 TI - Towards an integrated approach to marine benthic monitoring. AB - In the UK, most marine benthic monitoring is carried out in a piecemeal fashion, funded by different sectors of industry that utilise the marine environment under licence. Monitoring requirements are imposed by licence conditions, which can vary considerably between licences. The UK Government also conducts marine environmental surveys in support of its legislative commitments. The present investigation reviews these different monitoring approaches to highlight whether synergies between them could be developed into an integrated approach to marine benthic monitoring. An integrated approach would have ecological benefits, as greater consistency in sampling and analytical protocols would reduce uncertainty in the predictions of impact, and facilitate the assessment of Good Environmental Status under the Marine Strategy Framework Directive. The same approach would also be of financial benefit, as spatio-temporal duplication in sampling would be reduced, and the value of acquired data would be maximised, resulting in a more efficient and cost-effective approach. PMID- 26856641 TI - Shark parasites as bio-indicators of metals in two South African embayments. AB - Concentrations of metals in the tissues of the sharks Callorhinchus capensis, Rhinobatos annulatus and Rhinobatos blochii collected in False Bay and Saldanha Bay, South Africa, in 2013 were investigated. Metal concentrations in the tissue of the parasites Gyrocotyle plana infecting the spiral intestine of C. capensis and Proleptus obtusus infecting the stomach of R. annulatus and R. blochii were also analysed. G. plana showed accumulation of arsenic (4073.52+/-5561.54 MUg/g), manganese (522.16+/-578.21 MUg/g), lead (64.87+/-101.7 MUg/g), titanium (1821.42+/-1348.16 MUg/g) and zinc (12439.57+/-9743.60 MUg/g). These results when compared to baseline values, showed that accumulation of the metals in G. plana are orders of magnitude higher than those in the surrounding environment and 2 to 6 times the concentration of the surrounding host's tissues. These results show the usefulness of marine endoparasites as early warning indicators of heavy metal pollution. PMID- 26856643 TI - The expansion of Ulva prolifera O.F. Muller macroalgal blooms in the Yellow Sea, PR China, through asexual reproduction. AB - Since 2007, Ulva macroalgal blooms have occurred along the coastal areas of the Yellow Sea, China. These blooms are dominated by fragments of Ulva prolifera in the early stages of development. The objectives of this study were to identify the primary mode of asexual reproduction for U. prolifera and to evaluate the contribution of these thalli fragments to the formation of blooms. Four different growth and reproductive strategies of U. prolifera segments were found including: 1) tubular diameter becoming larger; 2) formation of new branches; 3) release of zoids; and 4) polarized growth. This is the first report showing the development of numerous blade-lets from a single segment, which is remarkably different from previous studies on other Ulva species. The results in the present study provide critical information to understand how this species is able to support its explosive growth during a bloom. PMID- 26856645 TI - Reducing spatial variation in environmental assessment of marine benthic fauna. AB - The Benthic Quality Index, BQI, is widely used for benthic quality assessment. Here, we investigated if spatial variation in the BQI can be reduced by accounting for the environmental factors instead of having different boundaries for different salinity regimes between status classes in the EU Water Framework Directive and Marine Strategy Framework Directive. For this purpose we tested salinity, sediment structure, and depth in a regression model to test their contribution to variations in BQI. The spatial variation in BQI was better explained by depth than by salinity or sediment structure. The proposed assessment method uses the residuals from the regression model between BQI and depth. With this method the variance in BQI between samples was reduced by 50% to 75% in the majority of situations. A method to establish the boundary between good and moderate status and how to derive EQR-values according to the WFD is presented. PMID- 26856644 TI - Prediction of the bioaccumulation of PAHs in surface sediments of Bohai Sea, China and quantitative assessment of the related toxicity and health risk to humans. AB - Assessing the health risk of PAHs in sediments was quite difficult because sediment occurred in sea floor, and it was very hard to contact with them directly for humans. This study was attempted to reveal the relationship between concentrations of PAHs in surface sediments and health risk of seafood consumers. The transfer (bioaccumulation) of PAHs from surface sediment into benthic organisms was predicted. Source contributions to PAHs and related toxicity and health risks (from intake of PAHs-contaminated benthic organisms) were studied based on PMF model and Monte Carlo simulation, respectively. Total concentrations of PAHs (TPAHs) ranged from 149.40 to 1211.97 ng g(-1) in sediments of Bohai Sea (BS), China. Petroleum and vehicular emission, coal combustion and coke oven constituted 40.0%, 32.2% and 27.8% of PAHs, respectively, but contributed 53.0%, 22.8% and 24.2% of toxicity posed by PAHs in sediment. For children, teens and adults, the 95th percentile carcinogenic and non-carcinogenic risks were below the threshold values of 10(-6) and 1.0, respectively, suggesting no potential health risk. Sensitivity analysis suggested that exposure duration (ED) and PAH concentrations (CS) were the two most sensitive parameters in risk assessment. The results provided a method to evaluate the quality of sediments and the potential health risk related to PAHs in marine sediments. PMID- 26856646 TI - A study on the recovery of Tobago's coral reefs following the 2010 mass bleaching event. AB - In 2010, severe coral bleaching was observed across the southeastern Caribbean, including the island of Tobago, where coral reefs are subject to sedimentation and high nutrient levels from terrestrial runoff. Here we examine changes in corals' colony size distributions over time (2010-2013), juvenile abundances and sedimentation rates for sites across Tobago following the 2010 bleaching event. The results indicated that since pre-bleaching coral cover was already low due to local factors and past disturbance, the 2010 event affected only particular susceptible species' population size structure and increased the proportion of small sized colonies. The low density of juveniles (mean of 5.4+/-6.3 juveniles/m(-2)) suggests that Tobago's reefs already experienced limited recruitment, especially of large broadcasting species. The juvenile distribution and the response of individual species to the bleaching event support the notion that Caribbean reefs are becoming dominated by weedy non-framework building taxa which are more resilient to disturbances. PMID- 26856647 TI - Contamination, toxicity and speciation of heavy metals in an industrialized urban river: Implications for the dispersal of heavy metals. AB - Urban rivers are often utilized by the local residents as water source, but they can be polluted by heavy metals due to industrialization. Here, the concentrations, toxicity, speciation and vertical profiles of heavy metals in sediment were examined to evaluate their impact, dispersal and temporal variation in Dongbao River. Results showed that the sediment in the industrialized areas was seriously contaminated with Cr, Cu and Ni which posed acute toxicity. Heavy metals, except Cr and Pb, were mainly associated with non-residual fractions, indicating their high mobility and bioavailability. The non-industrialized areas were also seriously contaminated, suggesting the dispersal of heavy metals along the river. The surface sediment could be more contaminated than the deep sediment, indicating the recent pollution events. Overall, when the point sources are not properly regulated, intense industrialization can cause both serious contamination and dispersal of heavy metals, which have far-reaching consequences in public health and environment. PMID- 26856648 TI - Relationship between vitamin D and body fat distribution evaluated by DXA in postmenopausal women. AB - OBJECTIVE: The aim of this study was to explore the relationship between 25 hydroxyvitamin D (25[OH]D) serum concentrations and body fat distribution in a sample of postmenopausal women. METHODS: We enrolled sixty-two postmenopausal women; 25(OH)D serum concentrations, serum intact parathyroid hormone, blood analyses, and anthropometric measurements were carried out. Body fat composition was evaluated by dual-energy X-ray absorptiometry. Insulin resistance was estimated by homeostatic model assessment of insulin resistance (HOMA-IR) calculation. RESULTS: Low levels of vitamin D (<30 ng/mL) were found in 77.4% of the population studied. There was a correlation (P < 0.0001) between 25(OH)D and waist circumference (r = -0.543), android fat to gynoid fat (A/G) ratio (r = 0.554), high-density lipoprotein cholesterol (r = 0.498), and HOMA-IR (r = 0.520). A/G fat ratio (B = -34.90; 95% confidence interval [-55.30, -14.1]; P = 0.019), HOMA-IR (B = -3.17; 95% confidence interval [-5.99, -0.351]; P = 0.028), and high-density lipoprotein cholesterol (B = 0.361; 95% confidence interval [0.033, 0.698]; P = 0.032), were found to be independent predictors of lower 25(OH)D by multilogistic regression analysis. Except for waist circumference, both these results were maintained when correlations were adjusted for age, onset of menopause, serum intact parathyroid hormone, and medications, and when body mass index was added as covariate. CONCLUSIONS: Vitamin D deficiency and insufficiency are common conditions. A/G ratio appeared to be associated with 25(OH)D concentrations and it is well-known that the android disposition of body fat is more closely associated with the onset of metabolic syndrome. Longitudinal studies are needed to better characterize the direction and the causal links of this association. PMID- 26856649 TI - Nutritional habits, lifestyle, and genetic predisposition in cardiovascular and metabolic traits in Turkish population. AB - OBJECTIVES: Cardiovascular and metabolic traits (CMT) are influenced by complex interactive processes including diet, lifestyle, and genetic predisposition. The present study investigated the interactions of these risk factors in relation to CMTs in the Turkish population. METHODS: We applied bootstrap agglomerative hierarchical clustering and Bayesian network learning algorithms to identify the causative relationships among genes involved in different biological mechanisms (i.e., lipid metabolism, hormone metabolism, cellular detoxification, aging, and energy metabolism), lifestyle (i.e., physical activity, smoking behavior, and metropolitan residency), anthropometric traits (i.e., body mass index, body fat ratio, and waist-to-hip ratio), and dietary habits (i.e., daily intakes of macro- and micronutrients) in relation to CMTs (i.e., health conditions and blood parameters). RESULTS: We identified significant correlations between dietary habits (soybean and vitamin B12 intakes) and different cardiometabolic diseases that were confirmed by the Bayesian network-learning algorithm. Genetic factors contributed to these disease risks also through the pleiotropy of some genetic variants (i.e., F5 rs6025 and MTR rs180508). However, we also observed that certain genetic associations are indirect since they are due to the causative relationships among the CMTs (e.g., APOC3 rs5128 is associated with low-density lipoproteins cholesterol and, by extension, total cholesterol). CONCLUSIONS: Our study applied a novel approach to integrate various sources of information and dissect the complex interactive processes related to CMTs. Our data indicated that complex causative networks are present: causative relationships exist among CMTs and are affected by genetic factors (with pleiotropic and non-pleiotropic effects) and dietary habits. PMID- 26856650 TI - High-fat diet increases ghrelin-expressing cells in stomach, contributing to obesity. AB - OBJECTIVES: Mechanisms of high-fat diet (HFD)-induced obesity may involve ghrelin, an orexigenic and adipogenic hormone secreted by the stomach. Previous studies showed that obese subjects may display higher numbers of ghrelin producing cells and increased affinity of plasma immunoglobulins (Ig) for ghrelin, protecting it from degradation. The aim of this study was to determine if a HFD in mice would increase the number of ghrelin-expressing cells and affinity of ghrelin-reactive IgG. METHODS: Obesity in mice was induced by consumption of a 13-wk HFD. The number of preproghrelin mRNA-expressing cells in the stomach was analyzed by in situ hybridization and compared with chow-fed, nonobese controls and with genetically obese ob/ob mice. Affinity of ghrelin reactive IgG was analyzed using surface plasmon resonance. Plasma levels of ghrelin and des-acyl ghrelin were measured. RESULTS: HFD resulted in 30% of body fat content versus only 8% in controls (P < 0.001). The number of preproghrelin mRNA-producing cells was 15% (P < 0.05) higher in HFD-fed mice than in controls, contrasting with ob/ob mice, having a 41% (P < 0.001) decrease. Both models of obesity had normal plasma levels of ghrelin but a decrease of its des-acylated form. Ghrelin-reactive IgG affinity was found in the micromolar range with mean values of the dissociation equilibrium constant 1.5-fold (P < 0.05) lower in HFD fed versus control mice. CONCLUSION: Results from the present study showed that HFD in mice induces obesogenic changes, including increased numbers of ghrelin precursor-expressing cells and increased affinity of ghrelin-reactive IgG. Such changes may contribute to the mechanisms of HFD-induced obesity. PMID- 26856652 TI - A 20-Year-Old-Male with Hemorrhagic Shock. AB - Hemorrhagic shock from trauma is a leading cause of morbidity and mortality and commonly encountered by HEMS agencies. Understanding of the management of patients in hemorrhagic shock transported from the scene and interfacility transfers is important for all critical care providers. PMID- 26856653 TI - Mechanical Ventilation: History and Harm. PMID- 26856654 TI - That Transport Was Appropriate, Wasn't It? PMID- 26856655 TI - Articles That May Change Your Practice: Fatigue, Health, and Well-being. PMID- 26856656 TI - Real Heroes. PMID- 26856657 TI - Difficult Intubation Factors in Prehospital Rapid Sequence Intubation by an Australian Helicopter Emergency Medical Service. AB - OBJECTIVE: Prehospital rapid sequence intubation (RSI) of critically ill trauma patients is a high-risk procedure that may be associated with an increased rate of severe complications such as failed intubation, failure of oxygenation, hypoxia, hypotension, or need for surgical airway. The objective of this study was to describe the factors associated with difficult intubation in prehospital RSI as defined by more than a single look at laryngoscopy to achieve tracheal intubation. METHODS: This is an observational study using prospectively collected data. RESULTS: Four hundred forty-three RSIs were performed. Paramedics were the initial laryngoscopist in 290 (65.5%). First-look laryngoscopy resulted in successful tracheal intubation (TI) in 372 (84.0%) (95% confidence interval, 80.3%-87.1%). Intubation was achieved on second look at laryngoscopy in 58 (13.1%). "First-pass" TI was achieved in 394 (88.9%). Overall, successful TI was achieved in 438 (98.9%) (95% confidence interval, 97.4%-99.5%). Complications occurred in 116 (26.2%), with desaturation the commonest in 77 (17.4%). CONCLUSION: Factors associated with more than 1 look at laryngoscopy before TI included paramedic laryngoscopist and the presence of at least 1 of the following indicators: blood/vomitus in the airway, limited mouth opening, and limited neck movement. Trauma to face/neck, obese body habitus, C-spine precautions, cricoid pressure, midline stabilization, and intubation on the ground did not influence the level of difficulty encountered. PMID- 26856658 TI - Spinal Cord Injuries and Helicopter Emergency Medical Services, 6,929 Patients: A Multicenter Analysis. AB - OBJECTIVE: Traumatic spinal cord injury (SCI) impacts quality of life for patients and caregivers, generating lifetime costs in the millions. Previous studies show delayed treatment of SCI patients at specialized centers is linked to complicated outcomes and extended hospitalizations. This study characterizes helicopter emergency medical service (HEMS) use in SCI and develops a methodology to study large volumes of HEMS electronic medical record data from multiple providers. METHODS: This descriptive study used deidentified data of HEMS providers that use Golden Hour Data Systems, Inc (San Diego, CA) software service from 34 states in the United States from 2004 to 2011. Demographic and logistical data underwent a deidentification protocol developed specifically for this study before analysis. RESULTS: Six thousand nine hundred twenty-nine SCI patients were transported. HEMS use increased but decreased relative to total transports from 2004 to 2011. The average patient was 39 +/- 21 years old, male, and had a 63 minute total transport time. The largest age bracket was 15 to 25 years. CONCLUSION: HEMS improved access for SCI patients to all localities and generally took under 2 hours. SCI patients are mostly young adult males, thus supporting the loss of years of productivity and also supporting the high lifetime cost for care for SCI. This study created a methodology for future multicenter aggregate data studies. PMID- 26856659 TI - Comparison of Transferred Versus Nontransferred Pediatric Patients Admitted for Sepsis. AB - OBJECTIVE: Little is known about the characteristics of pediatric patients transferred for medical care. Thus, we aimed to compare pediatric patients admitted for sepsis as transfers versus those who were not admitted as transfers. METHODS: Retrospective study using The Agency for Healthcare Research and Quality 2009 Kids' Inpatient Database. Inclusion diagnosis of sepsis based on an All Patient Refined Diagnosis-Related Group of 720: Septicemia & Disseminated Infections resulted in 16,894 patients. Transfer status was based on admission codes. Weighted statistical analysis was conducted using STATA 12.1 (Stata Corporation, College Station, TX). Institutional review board approval was obtained. RESULTS: Weighted analysis found significant differences between transferred versus nontransferred patients in the following areas: highest severity of illness subclass (45.1% vs. 18.7%, P < .001), number of chronic conditions (2.0 vs. 1.5, P < .001), teaching hospital status (85.9% vs. 54.8%, P < .001), length of stay (10.8 vs. 6.5, p<.001), number of procedures (2.9 vs. 1.4, P < .001), mortality (8.4% vs. 3.2%, P < .001), total costs ($30,626 vs. $13,677, P < .001), and daily costs ($2,901 vs. $1,887, P < .001). CONCLUSION: Our study found that patients diagnosed with sepsis and transferred are more severely ill with a higher number of chronic conditions, longer lengths of stay, more procedures performed, higher mortality, and higher total and daily costs. PMID- 26856660 TI - Role of beta-catenin in development of bile ducts. AB - Beta-catenin is known to play stage- and cell-specific functions during liver development. However, its role in development of bile ducts has not yet been addressed. Here we used stage-specific in vivo gain- and loss-of-function approaches, as well as lineage tracing experiments in the mouse, to first demonstrate that beta-catenin is dispensable for differentiation of liver precursor cells (hepatoblasts) to cholangiocyte precursors. Second, when beta catenin was depleted in the latter, maturation of cholangiocytes, bile duct morphogenesis and differentiation of periportal hepatocytes from cholangiocyte precursors was normal. In contrast, stabilization of beta-catenin in cholangiocyte precursors perturbed duct development and cholangiocyte differentiation. We conclude that beta-catenin is dispensable for biliary development but that its activity must be kept within tight limits. Our work is expected to significantly impact on in vitro differentiation of stem cells to cholangiocytes for toxicology studies and disease modeling. PMID- 26856662 TI - The avian embryo to study development of the cardiac conduction system. AB - The avian embryo has long been a popular model system in developmental biology. The easy accessibility of the embryo makes it particularly suitable for in ovo microsurgery and manipulation. Re-incubation of the embryo allows long-term follow-up of these procedures. The current review focuses on the variety of techniques available to study development of the cardiac conduction system in avian embryos. Based on the large amount of relevant data arising from experiments in avian embryos, we conclude that the avian embryo has and will continue to be a powerful model system to study development in general and the developing cardiac conduction system in particular. PMID- 26856661 TI - Modeling renal progenitors - defining the niche. AB - Significant recent advances in methodologies for the differentiation of pluripotent stem cells to renal progenitors as well as the definition of niche conditions for sustaining those progenitors have dramatically enhanced our understanding of their biology and developmental programing, prerequisites for establishing viable approaches to renal regeneration. In this article, we review the evolution of culture techniques and models for the study of metanephric development, describe the signaling mechanisms likely to be driving progenitor self-renewal, and discuss current efforts to generate de novo functional tissues, providing in depth protocols and niche conditions for the stabilization of the nephronic Six2+progenitor. PMID- 26856663 TI - The impact of occlusal plane cant along with gingival display on smile attractiveness. AB - OBJECTIVES: To evaluate the influence of occlusal plane cant in conjunction with maxillary gingival display on perception of smile attractiveness by orthodontists, dentists, and laypersons. SETTING AND SAMPLE POPULATION: Faculty of Dentistry at Baskent University. A total of 204 raters for smile attractiveness. MATERIALS AND METHODS: A frontal intra-oral photograph of aligned teeth was modified using image processing software. Six different occlusal lines representing 0 degrees to 5 degrees cants were obtained by tilting the photographs. Each occlusal cant was adjusted in five manners resulting in five different gingival display amounts. Attractiveness of the 30 different smiles was evaluated by 204 raters divided into three groups (n = 68 in each group). RESULTS: Both occlusal cant (p < 0.001) and gingival display amount (p < 0.001) had a statistically significant influence on smile attractiveness. Smile attractiveness scores with reference to amount of gingival display showed a significant difference between rater groups (p < 0.001). Orthodontists preferred 1-mm coverage of upper central incisors by the upper lip, whereas dentists and laypersons preferred 2 mm. Significant (p < 0.001) interaction was observed between occlusal cant and gingival display amount, which influenced smile attractiveness. CONCLUSION: Increase in both occlusal plane cant and gingival display negatively influences smile attractiveness. The influence of occlusal plane cant becomes less when gingival display increases, whereas the influence of gingival display decreases when occlusal cant increases. Dentists are more generous than orthodontists, while laypersons are the most generous regarding smile attractiveness scores. PMID- 26856664 TI - Post-transplant survival in idiopathic pulmonary fibrosis patients concurrently listed for single and double lung transplantation. AB - BACKGROUND: Lung transplantation is a widely accepted treatment for patients with end-stage lung disease related to idiopathic pulmonary fibrosis (IPF). However, there are conflicting data on whether double lung transplant (DLT) or single lung transplant (SLT) is the superior therapy in these patients. The purpose of this study was to determine whether actuarial post-transplant graft survival among IPF patients concurrently listed for DLT and SLT is greater for recipients undergoing the former or the latter. METHODS: The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant candidates with IPF listed between January 1, 2001 and December 31, 2009 (n = 3,411). The study population included 1,001 (29.3%) lung transplant recipients concurrently listed for DLT and SLT, all >=18 years of age. The primary outcome measure was actuarial post-transplant graft survival, expressed in years. RESULTS: Among the study population, 433 (43.26%) recipients underwent SLT and 568 (56.74%) recipients underwent DLT. The analysis included 2,722.5 years at risk, with median graft survival of 5.31 years. On univariate (p = 0.317) and multivariate (p = 0.415) regression analyses, there was no difference in graft survival between DLT and SLT. CONCLUSIONS: Among IPF recipients concurrently listed for DLT and SLT, there is no statistical difference in actuarial graft survival between recipients undergoing DLT vs SLT. This analysis suggests that increased use of SLT for IPF patients may increase the availability of organs to other candidates, and thus increase the net benefit of these organs, without measurably compromising outcomes. PMID- 26856665 TI - Right atrial pressure/pulmonary artery wedge pressure ratio: A more specific predictor of survival in pulmonary arterial hypertension. AB - BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive, fatal disease. Current prognostic models are not ideal, and identifying more accurate prognostic variables is needed. The objective of this study was to evaluate the relative prognostic value of the right atrial pressure/pulmonary artery wedge pressure (RAP/PAWP) ratio in PAH patients. We hypothesized that the RAP/PAWP ratio is more predictive of survival than any of the other measured or calculated hemodynamic variables. METHODS: We performed a secondary analysis of a PAH cohort (Cohort 1) and validated our results in a separate cohort (Cohort 2). Cohort 1 included primarily patients enrolled in prospective, short-term, randomized clinical trials and subsequently followed long term. Cohort 2 included patients prospectively enrolled in a PAH registry at a tertiary PAH referral center. RESULTS: Cohort 1 (n = 847) and Cohort 2 (n = 697) had a mean age of 47 and 54 years, respectively. Most were female (78% and 73%, respectively), Caucasian (83% and 82%), with advanced functional class disease status (New York Heart Association Functional Class III/IV 85% and 68%) and with significantly elevated hemodynamics (mean RAP/PAWP ratio: 1.2 and 1.0; pulmonary vascular resistance: 13.5 and 9.4 Wood units). RAP/PAWP ratio indicated a 1-year hazard ratio of 1.44 (p = 0.0001) and 1.35, respectively (p < 0.0001), and was the most consistently predictive hemodynamic variable across the 2 cohorts. These results remain valid even when adjusted for other covariables in multivariable regression models. CONCLUSIONS: The RAP/PAWP ratio is a more specific predictor of survival than any other hemodynamic variable, and we recommend that it be used in clinical prognostication and PAH predictive models. PMID- 26856666 TI - Development of B-cell memory in early childhood and the impact on antigen specific tolerance after heart transplantation. AB - BACKGROUND: Young children show better survival after heart transplant compared with older individuals and can receive heart transplants safely from ABO incompatible donors. Children develop immunologic tolerance to donor ABH antigens reflected in persistent absence of specific antibodies. We hypothesized that immature T-independent B-cell response and lack of B-cell memory play a crucial role in tolerance of ABH antigens after ABOi transplants. METHODS: We determined phenotypes of splenic lymphocytes from adults and children and peripheral blood from ABO-incompatible or ABO-compatible heart transplant recipients and control subjects by flow cytometry. In vitro immune response to T-independent stimulation, erythrocytes, and ABH antigens was assessed using proliferation assays. RESULTS: A predominant role for CD27(+) B cells in T-independent activation was demonstrated; these cells were significantly less frequent in infants than older subjects. Only IgM(+)CD27(+) B cells proliferated in response to non-self erythrocytes. In blood, IgM(+) and switched IgM(-) memory B cells were rare in infants, increasing to near-adult levels in children 5 years old. IgM(+)CD27(+) B cells were significantly fewer in ABO-incompatible transplant recipients than in ABO-compatible recipients. CONCLUSIONS: CD27(+) cells play a key role in T-independent B-cell activation. Response to ABH antigens is mediated by IgM(+)CD27(+) B cells, and donor ABO-specific tolerance after ABO-incompatible transplantation in children is facilitated by low prevalence of these cells. The pattern of B-cell memory development is altered after ABO-incompatible transplant. Memory B cells may be quantified to assess eligibility for ABO incompatible transplant and represent a potential therapeutic target to extend the benefits of the immature immune system to older age groups. PMID- 26856668 TI - Trends and outcomes of patients with adult congenital heart disease and pulmonary hypertension listed for orthotopic heart transplantation in the United States. AB - BACKGROUND: Heart transplantation is increasing in patients with adult congenital heart disease (ACHD). In this population, the association of pulmonary hypertension (PH) with post-transplant outcomes is not well-defined. METHODS: Using data from the United Network for Organ Sharing database (1987 to 2014), we identified ACHD patients listed for heart transplantation, and examined survival between those with and without PH (pre-transplant PH defined as transpulmonary pressure gradient >12 mm Hg). RESULTS: Among 983 ACHD patients, 216 (22%) had PH. At time of listing, PH patients had a transpulmonary pressure gradient of 17.0 mm Hg vs 6.0 mm Hg (p < 0.01) in the no-PH group. Although left ventricular assist device (LVAD) use was infrequent, 3.1% of PH patients were treated with an LVAD versus 6.8% of the no-PH patients. Days from listing to transplant, days from listing to death on the waitlist and length of post-transplant hospitalization were not significantly different between the PH and no-PH groups. However, PH was associated with higher waitlist mortality (HR 1.73, CI 1.25 to 2.41). Pre transplant PH was not associated with post-transplant mortality at 30 days (HR 0.51, CI 0.23 to 1.13), 1 year (HR 0.68, 95% CI 0.40 to 1.18) or 5 years (HR 0.84, 95% CI 0.55 to 1.29). CONCLUSIONS: PH is common among ACHD patients listed for transplant and is associated with increased waitlist mortality. Conversely, PH was not associated with worse survival after transplant. Bridge-to-transplant LVAD therapy was uncommon in this ACHD population. PMID- 26856667 TI - The relationship between plasma lipid peroxidation products and primary graft dysfunction after lung transplantation is modified by donor smoking and reperfusion hyperoxia. AB - BACKGROUND: Donor smoking history and higher fraction of inspired oxygen (FIO2) at reperfusion are associated with primary graft dysfunction (PGD) after lung transplantation. We hypothesized that oxidative injury biomarkers would be elevated in PGD, with higher levels associated with donor exposure to cigarette smoke and recipient hyperoxia at reperfusion. METHODS: We performed a nested case control study of 72 lung transplant recipients from the Lung Transplant Outcomes Group cohort. Using mass spectroscopy, F2-isoprostanes and isofurans were measured in plasma collected after transplantation. Cases were defined in 2 ways: grade 3 PGD present at day 2 or day 3 after reperfusion (severe PGD) or any grade 3 PGD (any PGD). RESULTS: There were 31 severe PGD cases with 41 controls and 35 any PGD cases with 37 controls. Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (28.6 pg/ml vs 19.8 pg/ml, p = 0.03). Plasma F2-isoprostane levels were higher in severe PGD cases compared with controls (29.6 pg/ml vs 19.0 pg/ml, p = 0.03) among patients reperfused with FIO2 >40%. Among recipients of lungs from donors with smoke exposure, plasma F2 isoprostane (38.2 pg/ml vs 22.5 pg/ml, p = 0.046) and isofuran (66.9 pg/ml vs 34.6 pg/ml, p = 0.046) levels were higher in severe PGD compared with control subjects. CONCLUSIONS: Plasma levels of lipid peroxidation products are higher in patients with severe PGD, in recipients of lungs from donors with smoke exposure, and in recipients exposed to higher Fio2 at reperfusion. Oxidative injury is an important mechanism of PGD and may be magnified by donor exposure to cigarette smoke and hyperoxia at reperfusion. PMID- 26856669 TI - Influence of durable mechanical circulatory support and allosensitization on mortality after heart transplantation. AB - BACKGROUND: Allosensitization has been shown to negatively affect post-heart transplant (HTx) survival even with a negative crossmatch. Whether allosensitization related to mechanical circulatory support (MCS) is associated with worse post-HTx survival remains controversial. METHODS: Adult HTx recipients listed in the United Network for Organ Sharing database (July 2006-December 2012) were identified. Multivariate Cox regression assessed the effect of allosensitization on survival. Propensity matching was performed to compare patients who were and were not allosensitized. Kaplan-Meier survival analysis compared matched and unmatched patients in the MCS and medically managed cohorts. RESULTS: We identified 11,840 HTx recipients, of whom 4,167 had MCS. MCS was associated with allosensitization in multivariate logistic regression. Each different MCS device was associated with worse post-HTx survival in multivariate Cox regression. Allosensitization did not predict post-HTx mortality in MCS patients (hazard ratio, 1.07; 95% confidence interval, 0.89-1.28; p = 0.48. Among patients without MCS, allosensitization was associated with post-HTx mortality (hazard ratio, 1.19; 95% confidence interval, 1.03-1.39; p = 0.02). Kaplan-Meier analysis revealed equivalent survival in unmatched and matched cohorts when MCS patients who were allosensitized were compared with non-allosensitized MCS patients. Among non-MCS patients, allosensitization was associated with worse survival in unmatched and matched analysis. CONCLUSIONS: MCS was associated with allosensitization. For MCS patients, allosensitization did not independently predict worse post-HTx outcome. Among non-MCS patients, allosensitization was associated with worse post-HTx survival. Allosensitization appears to be a heterogeneous process influenced by presence of MCS. PMID- 26856670 TI - Implantable cardioverter-defibrillators in a heart transplant population: A single-center experience. PMID- 26856671 TI - Aortic vasculature changes following support with a continuous-flow left ventricular assist device: The role of pulsatility. PMID- 26856672 TI - Chronic thromboembolic pulmonary hypertension: From transplantation to distal pulmonary endarterectomy. PMID- 26856673 TI - Myocardial tissue engineering for cardiac repair. AB - The number of patients with heart failure is increasing in the aging population. Heart transplantation remains the only curative treatment option for patients with end-stage heart failure. Because of an organ donor shortage, new organ independent treatment options are necessary. Different approaches to cardiac repair therapies have been developed and optimized in recent years. One of these promising approaches is myocardial tissue engineering, which refers to the creation of 3-dimensional engineered heart tissue in vitro. This perspective provides an overview of different approaches to tissue engineering, including essentials to improve tissue quality and choice of ideal cell source, as well as an overview of in vitro and in vivo studies. Several hurdles that have to be overcome before clinical application of engineered heart tissue might become a realistic scenario are also addressed. PMID- 26856674 TI - Right heart failure after left ventricular assist devices: Surgical considerations. PMID- 26856675 TI - Echocardiographic parameters associated with right ventricular failure after left ventricular assist device: A review. AB - Left ventricular assist devices improve functional class and survival in selected patients with advanced heart failure, but right ventricular failure after surgery remains common and challenging to predict. Pre-operative echocardiography provides important information in the evaluation of patients before device implant. This review summarizes the data on this complex topic. PMID- 26856676 TI - Increased myeloid cell hypoxia-inducible factor-1 delays obliterative airway disease in the mouse. AB - BACKGROUND: Obliterative bronchiolitis after lung transplantation is characterized by chronic airway inflammation leading to the obliteration of small airways. Hypoxia-inducible factor-1 (HIF-1) is a master regulator of cellular responses to hypoxia and inflammation. The Von Hippel-Lindau protein (pVHL) drives the degradation of oxygen-sensitive subunit HIF-1alpha that controls the activity of HIF-1. We investigated the effect of myeloid cell-targeted gene deletion of HIF-1alpha or its negative regulator pVHL on the development of obliterative airway disease (OAD) in the recipients of tracheal allografts, a mouse model for obliterative bronchiolitis after lung transplantation. METHODS: Tracheal allografts were heterotopically transplanted from BALB/c donor mice to fully major histocompatibility complex-mismatched recipient mice with HIF-1alpha or VHL gene deletion in myeloid cells. The recipients were left non immunosuppressed or received tacrolimus daily. Histologic, immunohistochemical, and real-time reverse transcription polymerase chain reaction analyses were performed at 3, 10, and 30 days. RESULTS: In the absence of immunosuppression, myeloid cell-specific VHL deficiency of the recipient mice improved epithelial recovery, decreased inflammatory cell infiltration and expression of pro inflammatory cytokines, increased regulatory forkhead box P3 messenger RNA expression, and reduced OAD development in tracheal allografts. In the presence of tacrolimus immunosuppression, loss of HIF-1alpha activity in myeloid cells of the recipient by HIF-1alpha gene deletion accelerated OAD development in mouse tracheal allografts. CONCLUSIONS: Activity of the HIF-pathway affects the development of allograft rejection, and our results suggest that myeloid cell specific VHL-deficiency that potentially increases HIF-activity decreases allograft inflammation and the subsequent development of OAD in mouse tracheal allografts. PMID- 26856677 TI - Pycnodysostosis presenting as atypical stridor. AB - OBJECTIVES: Pycnodysostosis is a rare genetic disorder caused by a mutation of the cathepsin K gene involved in bone turnover. It is responsible, in particular, for a combination of dwarfism and bone fragility. Upper airway obstruction may be observed, but associated stridor has never been previously described. MATERIALS AND METHODS: Single-centre retrospective study over a period of 15 years with review of the literature. RESULTS: Three children (aged 2-18 months) were managed for stridor and obstructive sleep apnoea syndrome confirmed by polysomnography. Physical examination of these children revealed stridor with laryngomalacia, characteristic dysmorphic features and failure to thrive. Patient 1 presented typical laryngomalacia treated by surgical section of the aryepiglottic folds. Patient 2 presented upper airway obstruction with a narrow nasopharynx and long soft palate, treated by surgery and noninvasive ventilation. Patient 3 presented moderate laryngomalacia and nasal obstruction, treated by surgery and noninvasive ventilation. CONCLUSION: The diagnosis of pycnodysostosis must be considered in the presence of atypical laryngomalacia associated with multifactorial upper airway obstruction, failure to thrive and dysmorphic syndrome. A genetics consultation is essential in these patients. PMID- 26856678 TI - Notice of Withdrawal: "Comparison of fit accuracy between Procera custom abutments and three implant systems" by Tiago de Morais Alves da Cunha, Roberto Paulo Correia de Araujo, Paulo Vicente Barbosa da Rocha and Rosa Maria Pazos Amoedo. PMID- 26856679 TI - Perspectives on embodiment and prosthetic incorporation in those with spinal cord injury: Comment on "The embodiment of assistive devices-from wheelchair to exoskeleton" by M. Pazzaglia and M. Molinari. PMID- 26856680 TI - Functional conservation and diversification of APETALA1/FRUITFULL genes in Brachypodium distachyon. AB - The duplicated grass APETALA1/FRUITFULL (AP1/FUL) genes have distinct but overlapping patterns of expression, suggesting their discrete roles in transition to flowering, specification of spikelet meristem identity and specification of floral organ identity. In this study, we analyzed the expression patterns and functions of four AP1/FUL paralogs (BdVRN1, BdFUL2, BdFUL3 and BdFUL4) in Brachypodium distachyon, a model plant for the temperate cereals and related grasses. Among the four genes tested, only BdVRN1 could remember the prolonged cold treatment. The recently duplicated BdVRN1 and BdFUL2 genes were expressed in a highly consistent manner and ectopic expressions of them caused similar phenotypes such as extremely early flowering and severe morphological alterations of floral organs, indicating their redundant roles in floral transition, inflorescence development and floral organ identity. In comparison, ectopic expressions of BdFUL3 and BdFUL4 only caused a moderate early flowering phenotype, suggesting their divergent function. In yeast two-hybrid assay, both BdVRN1 and BdFUL2 physically interact with SEP proteins but only BdFUL2 is able to form a homodimer. BdVRN1 also interacts weakly with BdFUL2. Our results indicate that, since the separation of AP1/FUL genes in grasses, the process of sub- or neo-functionalization has occurred and paralogs function redundantly and/or separately in flowering competence and inflorescence development. PMID- 26856681 TI - Special edition on positive emotions. PMID- 26856682 TI - Assessing Risk-Based Upper Limits of Melamine Migration from Food Containers. AB - Melamine contamination of food has become a major food safety issue because of incidents of infant disease caused by exposure to this chemical. This study was aimed at establishing a safety limit in Taiwan for the degree of melamine migration from food containers. Health risk assessment was performed for three exposure groups (preschool children, individuals who dine out, and elderly residents of nursing homes). Selected values of tolerable daily intake (TDI) for melamine were used to calculate the reference migration concentration limit (RMCL) or reference specific migration limit (RSML) for melamine food containers. The only existing values of these limits for international standards today are 1.2 mg/L (0.2 mg/dm2 ) in China and 30 mg/L (5 mg/dm2 ) in the European Union. The factors used in the calculations included the specific surface area of food containers, daily food consumption rate, body weight, TDI, and the percentile of the population protected at a given migration concentration limit (MCL). The results indicate that children are indeed at higher risk of melamine exposure at toxic levels than are other groups and that the 95th percentile of MCL (specific surface area = 5) for children aged 1-6 years should be the RMCL (0.07 mg/dm2 ) for protecting the sensitive and general population. PMID- 26856683 TI - Prevalence of biopsy-proven non-alcoholic fatty liver disease in severely obese subjects without metabolic syndrome. AB - Obesity is a major risk factor for non-alcoholic fatty liver disease (NAFLD). NAFLD encompasses simple fatty liver (FL) and non-alcoholic steatohepatitis (NASH) in its spectrum. NASH can progress to liver cirrhosis and is associated with liver cancer. Not all obese subjects have insulin resistance (IR) or develop metabolic syndrome (MS). This study evaluates the prevalence of NAFLD in severely obese subjects without MS. We retrospectively reviewed 445 charts from our database of severely obese subjects with clinical suspicion of NAFLD and who were selected for laparoscopic Roux-en-Y gastric bypass surgery. One hundred five subjects who did not have MS, as defined by the International Diabetes Foundation, based on comprehensive pre-operative metabolic evaluation were included. Liver biopsy specimens were evaluated for NAFLD. 24% of morbidly obese (mean body mass index [BMI] 48 kg m(-2) ) adult subjects (mean age 38 years) who underwent bariatric surgery did not have MS. NAFLD was identified in 77 (73%) on liver biopsy, out of which 59 (56%) were labelled as FL and 18 (17%) had histological diagnosis of NASH. Age, gender, race and BMI were the same among all groups. Among NAFLD subjects, 22% did not have any additional metabolic component of MS, while 36% had low high-density lipoprotein, 27% had hypertension, 8% had high triglycerides and 6% had hyperglycaemia. IR calculated by HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) and diagnosis of hyperglycaemia was statistically higher in NASH group compared to those who did not have NASH. NAFLD is highly prevalent in morbidly obese individuals who undergo bariatric surgery despite the absence of MS. Diagnosis of hyperglycaemia in such subjects suggests the presence of IR and may have underlying NASH, which is a progressive form of NAFLD. PMID- 26856685 TI - Validation of the prediction model for inhibitor development in PUPs with severe haemophilia A. PMID- 26856684 TI - Prostate cancer-derived cathelicidin-related antimicrobial peptide facilitates macrophage differentiation and polarization of immature myeloid progenitors to protumorigenic macrophages. AB - BACKGROUND: A growing body of evidence indicates a positive correlation between expression of human antimicrobial peptide leucin leucin 37 (LL-37) and progression of epithelial cancers, including prostate cancer (PCa). Although the molecular mechanisms for this correlation has not yet been elucidated, the primary function of LL-37 as a chemotactic molecule for innate immune effector cells suggests its possible association in coordinating protumorigenic mechanisms, mediated by tumor-infiltrating immune cells. METHODS: To investigate protumorigenic role(s) of cathelicidin-related antimicrobial peptide (CRAMP), a murine orthologue of LL-37, the present study compared tumor growth kinetics between mouse PCa cell lines with and without CRAMP expression (TRAMP-C1 and TRAMP-C1(CRAMP-sh) , respectively) in immunocompetent mice. CRAMP-mediated chemotaxis of different innate immune cell types to the tumor microenvironment (TME) was observed in vivo and confirmed by in vitro chemotaxis assay. The role of CRAMP in differentiation and polarization of immature myeloid progenitors (IMPs) to protumorigenic type 2 macrophages (M2) in TME was determined by adoptive transfer of IMPs into mice bearing CRAMP(+) and CRAMP(-) tumors. To differentiate protumorigenic events mediated by tumor-derived CRAMP from host immune cell-derived CRAMP, tumor challenge study was performed in CRAMP-deficient mice. To identify mechanisms of CRAMP function, macrophage colony stimulating factor (M-CSF) and monocyte chemoattractant protein 1 (MCP-1) gene expression was analyzed by QRT-PCR and STAT3 signaling was determined by immunoblotting. RESULTS: Significantly delayed tumor growth was observed in wild-type (WT) mice implanted with TRAMP-C1(CRAMP-sh) cells compared to mice implanted with TRAMP-C1 cells. CRAMP(+) TME induced increased number of IMP differentiation into protumorigenic M2 macrophages compared to CRAMP(-) TME, indicating tumor-derived CRAMP facilitates differentiation and polarization of IMPs toward M2. Tumor challenge study in CRAMP deficient mice showed comparable tumor growth kinetics with WT mice, suggesting tumor-derived CRAMP plays a crucial role in PCa progression. In vitro study demonstrated that overexpressed M-CSF and MCP-1 in TRAMP-C1 cells through CRAMP-mediated autocrine signaling, involving p65, regulates IMP-to-M2 differentiation/polarization through STAT3 activation. CONCLUSION: Altogether, the present study suggests that overexpressed CRAMP in prostate tumor initially chemoattracts IMPs to TME and mediates differentiation and polarization of early myeloid progenitors into protumorigenic M2 macrophages during PCa progression. Thus, selective downregulation of CRAMP in tumor cells in situ may benefit overcoming immunosuppressive mechanisms in PCa. PMID- 26856686 TI - Using gene expression from urine sediment to diagnose prostate cancer: development of a new multiplex mRNA urine test and validation of current biomarkers. AB - BACKGROUND: Additional accurate non-invasive biomarkers are needed in the clinical setting to improve prostate cancer (PCa) diagnosis. Here we have developed a new and improved multiplex mRNA urine test to detect prostate cancer (PCa). Furthermore, we have validated the PCA3 urinary transcript and some panels of urinary transcripts previously reported as useful diagnostic biomarkers for PCa in our cohort. METHODS: Post-prostatic massage urine samples were prospectively collected from PCa patients and controls. Expression levels of 42 target genes selected from our previous studies and from the literature were studied in 224 post-prostatic massage urine sediments by quantitative PCR. Univariate logistic regression was used to identify individual PCa predictors. A variable selection method was used to develop a multiplex biomarker model. Discrimination was measured by ROC curve AUC for both, our model and the previously published biomarkers. RESULTS: Seven of the 42 genes evaluated (PCA3, ELF3, HIST1H2BG, MYO6, GALNT3, PHF12 and GDF15) were found to be independent predictors for discriminating patients with PCa from controls. We developed a four-gene expression signature (HIST1H2BG, SPP1, ELF3 and PCA3) with a sensitivity of 77% and a specificity of 67% (AUC = 0.763) for discriminating between tumor and control urines. The accuracy of PCA3 and previously reported panels of biomarkers is roughly maintained in our cohort. CONCLUSIONS: Our four gene expression signature outperforms PCA3 as well as previously reported panels of biomarkers to predict PCa risk. This study suggests that a urinary biomarker panel could improve PCa detection. However, the accuracy of the panels of urinary transcripts developed to date, including our signature, is not high enough to warrant using them routinely in a clinical setting. PMID- 26856687 TI - Evidences for the action mechanism of angiotensin II and its analogs on Plasmodium sporozoite membranes. AB - Malaria is an infectious disease responsible for approximately one million deaths annually. Oligopeptides such as angiotensin II (AII) and its analogs are known to have antimalarial effects against Plasmodium gallinaceum and Plasmodium falciparum. However, their mechanism of action is still not fully understood at the molecular level. In the work reported here, we investigated this issue by comparing the antimalarial activity of AII with that of (i) its diastereomer formed by only d-amino acids; (ii) its isomer with reversed sequence; and (iii) its analogs restricted by lactam bridges, the so-called VC5 peptides. Data from fluorescence spectroscopy indicated that the antiplasmodial activities of both all-D-AII and all-D-VC5 were as high as those of the related peptides AII and VC5, respectively. In contrast, retro-AII had no significant effect against P. gallinaceum. Conformational analysis by circular dichroism suggested that AII and its active analogs usually adopted a beta-turn conformation in different solutions. In the presence of membrane-mimetic micelles, AII had also a beta-turn conformation, while retro-AII was random. Molecular dynamics simulations demonstrated that the AII chains were slightly more bent than retro-AII at the surface of a model membrane. At the hydrophobic membrane interior, however, the retro-AII chain was severely coiled and rigid. AII was much more flexible and able to experience both straight and coiled conformations. We took it as an indication of the stronger ability of AII to interact with membrane headgroups and promote pore formation. PMID- 26856688 TI - First total synthesis of WLIP: on the importance of correct protecting group choice. AB - Cyclic lipodepsipeptides (CLPs) are a group of metabolites produced by Pseudomonas bacteria, involved in various biological functions and displaying a wide range of properties, including antibacterial and antifungal activities. The white line-inducing principle (WLIP) is a member of the viscosin group featuring a Glu2 amino acid. Recently, a total synthesis of pseudodesmin A - the Gln2 counterpart of WLIP - was described, and we here expand this route to Glu2 containing CLPs. We report the first total synthesis of WLIP and at the same time establish that the Gln2 to Glu2 substitution has an adverse impact on the crude purity and overall yield. A comparative study of different CLP analogues reveals the importance of the nature of the Glx2 protecting group in determining these outcomes. Replacement of the conventional tBu protecting group by the larger benzyl group for the Glu residue in our synthesis strategy indeed resulted in an improved conversion. Next to achieving the first WLIP total synthesis, we thus show the importance of a careful choice of protecting groups for the success of this type of solid-phase synthesis approaches towards CLPs. PMID- 26856689 TI - Conformational transformation of ascidiacyclamide analogues induced by incorporating enantiomers of phenylalanine, 1-naphthylalanine or 2 naphthylalanine. AB - We designed five ascidiacyclamide analogues [cyclo(-Xxx(1) -oxazoline(2) -d Val(3) -thiazole(4) -l-Ile(5) -oxazoline(6) -d-Val(7) -thiazole(8) -)] incorporating l-1-naphthylalanine (l-1Nal), l-2-naphthylalanine (l-2Nal), d phenylalanine (d-Phe), d-1-naphthylalanine (d-1Nal) or d-2-naphthylalanine (d 2Nal) into the Xxx(1) position of the peptide. The conformations of these analogues were then examined using (1) H NMR, CD spectroscopy, and X-ray diffraction. These analyses suggested that d-enantiomer-incorporated ASCs [(d Phe), (d-1Nal), and (d-2Nal)ASC] transformed from the folded to the open structure in solution more easily than l-enantiomer-incorporated ASCs [(l-Phe), (l-1Nal), and (l-2Nal)ASC]. Structural comparison of the two analogues containing isomeric naphthyl groups showed that the 1-naphthyl isomer induced a more stable open structure than the 2-naphthyl isomer. In particular, [d-1Nal]ASC showed the most significant transformation from the folded to the open structure in solution, and exhibited the strongest cytotoxicity toward HL-60 cells. PMID- 26856690 TI - Crystal structure of a tripeptide containing aminocyclododecane carboxylic acid: a supramolecular twisted parallel beta-sheet in crystals. AB - The crystal structure of a tripeptide Boc-Leu-Val-Ac12 c-OMe (1) is determined, which incorporates a bulky 1-aminocyclododecane-1-carboxylic acid (Ac12 c) side chain. The peptide adopts a semi-extended backbone conformation for Leu and Val residues, while the backbone torsion angles of the C(alpha,alpha) -dialkylated residue Ac12 c are in the helical region of the Ramachandran map. The molecular packing of 1 revealed a unique supramolecular twisted parallel beta-sheet coiling into a helical architecture in crystals, with the bulky hydrophobic Ac12 c side chains projecting outward the helical column. This arrangement resembles the packing of peptide helices in crystal structures. Although short oligopeptides often assemble as parallel or anti-parallel beta-sheet in crystals, twisted or helical beta-sheet formation has been observed in a few examples of dipeptide crystal structures. Peptide 1 presents the first example of a tripeptide showing twisted beta-sheet assembly in crystals. PMID- 26856691 TI - Protein stabilizer, NDSB-195, enhances the dynamics of the beta4 -alpha2 loop of ubiquitin. AB - Non-detergent sulfobetaines (NDSBs) are a new group of small, synthetic protein stabilizers, which have advantages over classical compatible osmolytes, such as polyol, amines, and amino acids: they do not increase solution viscosity, unlike polyols, and they are zwitterionic at all pH ranges, unlike amines and amino acids. NDSBs also facilitate the crystallization and refolding of proteins. The mechanism whereby NDSBs exhibit such activities, however, remains elusive. To gain insight into this mechanism, we studied, using nuclear magnetic resonance (NMR), the effects of dimethylethylammonium propane sulfonate (NDSB-195) on the dynamics of ubiquitin, on which a wealth of information has been accumulated. By analyzing the line width of amide proton resonances and the transverse relaxation rates of nitrogen atoms, we found that NDSB-195 enhances the microsecond millisecond dynamics of a beta4 -alpha2 loop of ubiquitin. Although those compounds that enhance protein dynamics are generally considered to destabilize protein molecules, NDSB-195 enhanced the stability of ubiquitin against guanidium chloride denaturation. Thus, the simultaneous enhancement of stability and flexibility by a single compound can be attained. PMID- 26856692 TI - Identification and bioactivity evaluation of a novel bradykinin inhibitory peptide from the skin secretion of Chinese large odorous frog, Odorrana livida. AB - A novel peptide was isolated from the skin secretion of Chinese large odorous frog, Odorrana livida, and was named as Rana-BI. The cDNA sequencing was obtained by 'shotgun' cloning. The amino acid sequence of the mature peptide was identified as Gly-Leu-Leu-Ser-Gly-Lys-Ser-Val-Lys-Gly-Ser-Ile-OH by automated Edman degradation, and the molecular weight of the peptide was confirmed to be 1144.68 Da by MALDI-TOF and liquid chromatography/MS. Subsequently, the bioactivity of synthetic peptide was evaluated by smooth muscle assay using isolated rat bladder preparation. It was demonstrated that Rana-BI inhibited the contraction of rat bladder induced by bradykinin. Comparing with other peptides by searching from database, the primary structure of Rana-BI showed high similarity with that of an antimicrobial peptide of Rana family (12/12 residues). These data revealed a novel biological function of this peptide. PMID- 26856693 TI - Oxyma-based phosphates for racemization-free peptide segment couplings. AB - Glyceroacetonide-Oxyma [(2,2-dimethyl-1,3-dioxolan-4-yl)methyl 2-cyano-2 (hydroxyimino)acetate (1)] displayed remarkable physico-chemical properties as an additive for peptide-forming reactions. Although racemization-free amide-forming reactions have been established for N-urethane-protected alpha-amino acids with EDCI, 1, and NaHCO3 in water or DMF-water media, amide-forming reactions of N acyl-protected alpha-amino acids and segment couplings of oligopeptides still require further development. Diethylphosphoryl-glyceroacetonide-oxyma (DPGOx 3) exhibits relative stability in aprotic solvents and is an effective coupling reagent for N-acyl-protected alpha-amino acids and oligo peptide segments. The conditions reported here is also effective in lactam-forming reactions. Unlike most of the reported coupling reagents, simple aqueous work-up procedures can remove the reagents and by-products generated in the reactions. PMID- 26856694 TI - Does Order of Application of Emollient and Topical Corticosteroids Make a Difference in the Severity of Atopic Eczema in Children? AB - BACKGROUND: Atopic eczema (AE) is a common chronic inflammatory skin disorder in children, with emollients and topical corticosteroids (TCSs) commonly prescribed as treatment. There is no published guidance on the correct order of application of emollient and TCS in children with AE. OBJECTIVE: The objective of this study was to determine whether the order of application of emollient and TCS makes a difference in the severity of AE in children. METHODS: Forty-six patients ages 4 months to 5 years with moderate to severe AE were randomized to two groups: group A applied emollient followed by TCS 15 minutes later twice daily, and group B applied TCS followed by emollient 15 minutes later twice daily for 2 weeks. RESULTS: There was no statistically significant difference in the Eczema Area and Severity Index (EASI) score, percentage of body surface area (BSA) affected, or itch score between groups A and B (p > 0.05). Group A had statistically significant improvement in the EASI score, percentage BSA affected, and itch score from baseline to weeks 1 and 2; group B demonstrated statistically significant improvement only in the EASI score from baseline to week 1 and in itch score from baseline to week 2. There was no difference in adverse events between the groups. CONCLUSION: This study suggests that the order of application of emollient and TCS does not matter in the treatment of AE in children and that parents can apply topical medications in whichever order they prefer. PMID- 26856695 TI - The effects of pioglitazone adjuvant therapy on negative symptoms of patients with chronic schizophrenia: a double-blind and placebo-controlled trial. AB - OBJECTIVE: The evident central role of inflammation, oxidative stress, and metabolic derangement in pathophysiology of negative symptoms of schizophrenia has opened new insights into probable pharmacological options for these symptoms. Pioglitazone is an antidiabetic agent with anti-inflammatory and antioxidant properties. In this study, we evaluated the efficacy of pioglitazone as an adjunct to risperidone for reduction of negative symptoms in schizophrenia. METHODS: In this randomized, double-blind, placebo-controlled trial, 40 patients with chronic schizophrenia and a minimum score of 20 on the negative subscale of Positive and Negative Syndrome Scale (PANSS) were randomly allocated to receive risperidone plus either pioglitazone (30 mg/day) or placebo for 8 weeks. Patients' symptoms and adverse events were rated at baseline and weeks 2, 4, 6, and 8. The difference between the two groups in decline of PANSS negative subscale scores was considered as the primary outcome of this study. RESULTS: At the study endpoint, patients in the pioglitazone group showed significantly more improvement in PANSS negative subscale scores (p < 0.001) as well as PANSS total scores (p = 0.01) compared with the placebo group. CONCLUSION: These findings suggest the probable efficacy of pioglitazone as an augmentation therapy in reducing the negative symptoms of schizophrenia. PMID- 26856696 TI - Sodium thiosulfate attenuates glial-mediated neuroinflammation in degenerative neurological diseases. AB - BACKGROUND: Sodium thiosulfate (STS) is an industrial chemical which has also been approved for the treatment of certain rare medical conditions. These include cyanide poisoning and calciphylaxis in hemodialysis patients with end-stage kidney disease. Here, we investigated the anti-inflammatory activity of STS in our glial-mediated neuroinflammatory model. METHODS: Firstly, we measured glutathione (GSH) and hydrogen sulfide (H2S, SH(-)) levels in glial cells after treatment with sodium hydrosulfide (NaSH) or STS. We also measured released levels of tumor necrosis factor-alpha (TNFalpha) and interleukin-6 (IL-6) from them. We used two cell viability assays, MTT and lactate dehydrogenase (LDH) release assays, to investigate glial-mediated neurotoxicity and anti-inflammatory effects of NaSH or STS. We also employed Western blot to examine activation of intracellular inflammatory pathways. RESULTS: We found that STS increases H2S and GSH expression in human microglia and astrocytes. When human microglia and astrocytes are activated by lipopolysaccharide (LPS)/interferon-gamma (IFNgamma) or IFNgamma, they release materials that are toxic to differentiated SH-SY5Y cells. When the glial cells were treated with NaSH or STS, there was a significant enhancement of neuroprotection. The effect was concentration dependent and incubation time-dependent. Such treatment reduced the release of TNFalpha and IL-6 and also attenuated activation of P38 MAPK and NFkappaB proteins. The compounds tested were not harmful when applied directly to all the cell types. CONCLUSIONS: Although NaSH was somewhat more powerful than STS in these in vitro assays, STS has already been approved as an orally available treatment. STS may therefore be a candidate for treating neurodegenerative disorders that have a prominent neuroinflammatory component. PMID- 26856697 TI - IL-1 Receptor Signaling on Graft Parenchymal Cells Regulates Memory and De Novo Donor-Reactive CD8 T Cell Responses to Cardiac Allografts. AB - Reperfusion of organ allografts induces a potent inflammatory response that directs rapid memory T cell, neutrophil, and macrophage graft infiltration and their activation to express functions mediating graft tissue injury. The role of cardiac allograft IL-1 receptor (IL-1R) signaling in this early inflammation and the downstream primary alloimmune response was investigated. When compared with complete MHC-mismatched wild-type cardiac allografts, IL-1R(-/-) allografts had marked decreases in endogenous memory CD8 T cell and neutrophil infiltration and expression of proinflammatory mediators at early times after transplant, whereas endogenous memory CD4 T cell and macrophage infiltration was not decreased. IL 1R(-/-) allograft recipients also had marked decreases in de novo donor-reactive CD8, but not CD4, T cell development to IFN-gamma-producing cells. CD8 T cell mediated rejection of IL-1R(-/-) cardiac allografts took 3 wk longer than wild type allografts. Cardiac allografts from reciprocal bone marrow reconstituted IL 1R(-/-)/wild-type chimeric donors indicated that IL-1R signaling on graft nonhematopoietic-derived, but not bone marrow-derived, cells is required for the potent donor-reactive memory and primary CD8 T cell alloimmune responses observed in response to wild-type allografts. These studies implicate IL-1R-mediated signals by allograft parenchymal cells in generating the stimuli-provoking development and elicitation of optimal alloimmune responses to the grafts. PMID- 26856699 TI - Highly Accurate Sequencing of Full-Length Immune Repertoire Amplicons Using Tn5 Enabled and Molecular Identifier-Guided Amplicon Assembly. AB - Ab repertoire sequencing is a powerful tool to analyze the adaptive immune system. To sequence entire Ab repertoires, amplicons are created from Ab H chain (IgH) transcripts and sequenced on a high-throughput sequencer. The field of immune repertoire sequencing is growing rapidly and the protocols used are steadily improving; however, thus far, immune repertoire sequencing protocols have not been able to sequence full-length immune repertoires including the entire IgH V region and enough of the IgH C region to identify isotype subtypes. In this study, we present a method that combines Tn5 transposase and molecular identifiers for the highly accurate sequencing of amplicons >500 bp using Illumina short read paired-end sequencing. We then apply this method to Ab H chain amplicons to sequence the first, to our knowledge, highly accurate full length immune repertoire. PMID- 26856698 TI - LAMP-2C Inhibits MHC Class II Presentation of Cytoplasmic Antigens by Disrupting Chaperone-Mediated Autophagy. AB - Cells use multiple autophagy pathways to sequester macromolecules, senescent organelles, and pathogens. Several conserved isoforms of the lysosome-associated membrane protein-2 (LAMP-2) regulate these pathways influencing immune recognition and responses. LAMP-2A is required for chaperone-mediated autophagy (CMA), which promotes Ag capture and MHC class II (MHCII) presentation in B cells and signaling in T cells. LAMP-2B regulates lysosome maturation to impact macroautophagy and phagocytosis. Yet, far less is known about LAMP-2C function. Whereas LAMP2A and LAMP2B mRNA were broadly detected in human tissues, LAMP2C expression was more limited. Transcripts for the three LAMP2 isoforms increased with B cell activation, although specific gene induction varied depending on TLR versus BCR engagement. To examine LAMP-2C function in human B cells and specifically its role in Ag presentation, we used ectopic gene expression. Increased LAMP-2C expression in B cells did not alter MHCII expression or invariant chain processing, but did perturb cytoplasmic Ag presentation via CMA. MHCII presentation of epitopes from exogenous and membrane Ags was not affected by LAMP-2C expression in B cells. Similarly, changes in B cell LAMP-2C expression did not impact macroautophagy. The gene expression of other LAMP2 isoforms and proteasome and lysosomal proteases activities were unperturbed by LAMP-2C ectopic expression. LAMP-2C levels modulated the steady-state expression of several cytoplasmic proteins that are targeted for degradation by CMA and diminished peptide translocation via this pathway. Thus, LAMP-2C serves as a natural inhibitor of CMA that can selectively skew MHCII presentation of cytoplasmic Ags. PMID- 26856701 TI - A Leukocyte Immune-Type Receptor Subset Is a Marker of Antiviral Cytotoxic Cells in Channel Catfish, Ictalurus punctatus. AB - Channel catfish, Ictalurus punctatus, leukocyte immune type receptors (LITRs) represent a multigene family that encodes Ig superfamily proteins that mediate activating or inhibitory signaling. In this study, we demonstrate the use of mAb CC41 to monitor viral cytotoxic responses in catfish and determine that CC41 binds to a subset of LITRs on the surface of catfish clonal CTLs. Homozygous gynogenetic catfish were immunized with channel catfish virus (CCV)-infected MHC matched clonal T cells (G14D-CCV), and PBL were collected at various times after immunization for flow cytometric analyses. The percentage of CC41(+) cells was significantly increased 5 d after primary immunization with G14D-CCV and at 3 d after a booster immunization as compared with control fish only injected with G14D. Moreover, CC41(+) cells magnetically isolated from the PBL specifically killed CCV-infected targets as measured by (51)Cr release assays and expressed messages for CD3gammadelta, perforin, and at least one of the CD4-like receptors as analyzed by RNA flow cytometry. When MLC effector cells derived from a G14D CCV-immunized fish were preincubated with CC41 mAb, killing of G14D-CCV targets was reduced by ~40%, suggesting that at least some LITRs have a role in target cell recognition and/or cytotoxicity. The availability of a LITR-specific mAb has allowed, to our knowledge for the first time, functional characterization of LITRs in an autologous system. In addition, the identification of an LITR subset as a cytotoxic cell marker will allow for more effective monitoring of catfish immune responses to pathogens. PMID- 26856700 TI - Regulation of Adenosine Deaminase on Induced Mouse Experimental Autoimmune Uveitis. AB - Adenosine is an important regulator of the immune response, and adenosine deaminase (ADA) inhibits this regulatory effect by converting adenosine into functionally inactive molecules. Studies showed that adenosine receptor agonists can be anti- or proinflammatory. Clarification of the mechanisms that cause these opposing effects should provide a better guide for therapeutic intervention. In this study, we investigated the effect of ADA on the development of experimental autoimmune uveitis (EAU) induced by immunizing EAU-prone mice with a known uveitogenic peptide, IRBP1-20. Our results showed that the effective time to administer a single dose of ADA to suppress induction of EAU was 8-14 d postimmunization, shortly before EAU expression; however, ADA treatment at other time points exacerbated disease. ADA preferentially inhibited Th17 responses, and this effect was gammadelta T cell dependent. Our results demonstrated that the existing immune status strongly influences the anti- or proinflammatory effects of ADA. Our observations should help to improve the design of ADA- and adenosine receptor-targeted therapies. PMID- 26856702 TI - Exonic enhancers: proceed with caution in exome and genome sequencing studies. AB - Exonic enhancers (eExons) are coding exons that also function as enhancers of the gene in which they reside or (a) nearby gene(s). Mutations that affect the enhancer activity of these eExons have been associated with human disease. Therefore, eExon mutations should be taken into account in exome and genome sequencing projects, not only because of the ability of these mutations to modify the encoded proteins but also because of their effects on enhancer activity. PMID- 26856705 TI - Effects of conventional and orthodontic pacifiers on the dental occlusion of children aged 24-36 months old. AB - AIM: To investigate the effects of conventional and orthodontic pacifiers on the prevalence of malocclusion (MO) considering frequency, duration, and intensity of the sucking habit. DESIGN: Data were collected at three time-points: birth, T1; (12-24 months old), T2; (24-36 months old), T3 and were divided into three groups: control (GC; 110), without non-nutritive sucking habits; orthodontic pacifiers (GOrth; 55); conventional pacifiers (GConv; 55). A questionnaire was applied. Clinical examination was performed at T3. The groups were compared as to the prevalence and severity of anterior open bite (AOB), accentuated overjet, anterior crossbite, posterior crossbite (PCB). RESULTS: The use of pacifiers was associated with occurrence of MO compared to GC (P < 0.05). Frequency, intensity, and duration of pacifier use was also associated with of MO. There was significant difference in the prevalence of MO between GConv and GOrth for AOB (P = 0.027). Only GConv exhibited higher odds of PCB compared to GC (P = 0.040). The prevalence of MO was significantly higher in pacifiers users (P < 0.001). CONCLUSION: The prevalence of MO was higher among children who used pacifiers. According to a general trend, the use of conventional pacifiers was associated to severe anterior open bite and overjet. PMID- 26856703 TI - Impaired learning and memory in CD38 null mutant mice. AB - CD38 is an enzyme that catalyzes the formation of cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate, both of which are involved in the mobilization of Ca(2+) from intracellular stores. Recently, CD38 has been shown to regulate oxytocin release from hypothalamic neurons. Importantly, CD38 mutations are associated with autism spectrum disorders (ASD) and CD38 knockout (CD38(-/-)) mice display ASD-like behavioral phenotypes including deficient parental behavior and poor social recognition memory. Although ASD and learning deficits commonly co-occur, the role of CD38 in learning and memory has not been investigated. We report that CD38(-/-) mice show deficits in various learning and memory tasks such as the Morris water maze, contextual fear conditioning, and the object recognition test. However, either long-term potentiation or long-term depression is not impaired in the hippocampus of CD38(-/-) mice. Our results provide convincing evidence that CD38(-/-) mice show deficits in various learning and memory tasks including spatial and non-spatial memory tasks. Our data demonstrate that CD38 is critical for regulating hippocampus-dependent learning and memory without modulating synaptic plasticity. PMID- 26856704 TI - Differences in routine esophagogastroduodenoscopy between Japanese and international facilities: A questionnaire survey. AB - BACKGROUND AND AIM: The mortality rate of gastric cancer (GC) is close to the incidence rate worldwide. However, in Korea and Japan, the mortality rate of GC is less than half of the incidence rate. We hypothesized that good-quality routine esophagogastroduodenoscopy (EGD) contributes to a high detection rate for early GC (EGC) and improves mortality in these countries. METHODS: To clarify the differences in routine EGD, a questionnaire survey was conducted in 98 Japanese and 53 international institutions. RESULTS: Prevalence of screening examination among routine EGD was higher in Japanese than in international institutions. Japanese endoscopists noted that endoscopic mucosal atrophy was the most significant risk factor for GC, whereas international endoscopists paid more attention to clinical information such as age, symptoms and family history. Antispasmodics, mucolytics and defoaming agents were used more frequently in Japanese institutions. The examination time was similar (mostly 5-10 min) between Japanese and international institutions. Japanese endoscopists took more pictures (>20 in almost all institutions) than international endoscopists (<=20 in two thirds of institutions). In Japanese institutions, biopsy specimens were more frequently taken from areas of mucosal discoloration, unevenness or spontaneous bleeding rather than from obvious endoscopic lesions such as ulceration or polyps. In most Japanese institutions, one or two biopsy specimens were taken per lesion, compared with >=three in international institutions. CONCLUSION: There were some discrepancies between Japanese and international institutions for routine EGD. Thus, standardization is required for adequate risk assessment, proper techniques, and knowledge of endoscopic diagnosis of EGC. PMID- 26856706 TI - Effects of commonly used intravitreal anti-vascular endothelial growth factor drugs on mesenchymal stem cells derived from the limbus and ciliary body. AB - BACKGROUND: To investigate the effects of commonly used intravitreal anti vascular endothelial growth factor (anti-VEGF) antibodies on proliferation index and viability of mesenchymal stem cells derived from ciliary body and limbus (CB MSC and LMSC). METHODS: CB-MSCs and LMSCs were isolated from newborn rats' eyes, and they were expanded in medium by the explant method. Intravitreally used anti VEGF drugs, aflibercept, bevacizumab and ranibizumab were tested into the 16-well plates, respectively, at four different concentrations. After keeping them for 48 h, the proliferation indexes and viabilities of CB-MSCs and LMSCs were compared separately by Real-Time Cell Analyzer and Methylthiazoltetrazoli (MTT) test. RESULTS: Anti-VEGFs used at 5-times and 10-times of the standard clinical dosage caused statistically significant negative effects on proliferation indexes of CB MSCs and LMSCs at the 24th hour compared to control group. Only the anti-VEGF group that had 10-times dosage of those used clinically had a statistically significant negative effect on the viabilties of CB-MSCs and LMSCs. CONCLUSION: Administrations of high doses or repeated standard doses of intravitreal anti VEGF agents may affect the proliferation indexes and viabilities of CB-MSCs and LMSCs adversely. These novel findings deserve further in vivo investigations. PMID- 26856707 TI - Inhibitory control and the speech patterns of second language users. AB - Inhibitory control (IC), an ability to suppress irrelevant and/or conflicting information, has been found to underlie performance on a variety of cognitive tasks, including bilingual language processing. This study examines the relationship between IC and the speech patterns of second language (L2) users from the perspective of individual differences. While the majority of studies have supported the role of IC in bilingual language processing using single-word production paradigms, this work looks at inhibitory processes in the context of extended speech, with a particular emphasis on disfluencies. We hypothesized that the speech of individuals with poorer IC would be characterized by reduced fluency. A series of regression analyses, in which we controlled for age and L2 proficiency, revealed that IC (in terms of accuracy on the Stroop task) could reliably predict the occurrence of reformulations and the frequency and duration of silent pauses in L2 speech. No statistically significant relationship was found between IC and other L2 spoken output measures, such as repetitions, filled pauses, and performance errors. Conclusions focus on IC as one out of a number of cognitive functions in the service of spoken language production. A more qualitative approach towards the question of whether L2 speakers rely on IC is advocated. PMID- 26856708 TI - Chemical alterations and regulations of biomolecules in lifestyle-related diseases. AB - We know experientially that not only nutrient factors but also non-nutritive functional food factors are playing important roles in maintenance of homeostasis, health promotion, and disease prevention. Although some of these effective behaviors are supported by accumulating scientific evidences, it is in general difficult to determine properly in human. Therefore, the discovering of novel biomarker and developments of the analytical method are one of the prudent strategies to understand disease etiology and evaluate efficacies of functional food factors via monitoring the pathophysiological alteration in live body, tissue, and cells. This review describes recent our findings on (1) formation mechanism, bioactivities, quantitative determination of cholesterol ozonolysis product, secosterol as possible biomarker for lifestyle-related disease, and (2) chemical biology approach for the investigating molecular mechanisms of most promising cancer chemopreventive food factors, isothiocyanate-inducing bioactivities. PMID- 26856709 TI - Impact of CYP3A5 and MDR-1 gene polymorphisms on the dose and level of tacrolimus among living-donor liver transplanted patients: single center experience. AB - AIM OF WORK: To assess the impact of Cytochrome P450 3A5 (CYP3A5) and multidrug resistance-1 gene (MDR-1) single nucleotide polymorphisms on the dose and blood level of tacrolimus among liver transplanted patients. PATIENTS AND METHODS: We enrolled a prospective study of 41 liver transplanted patients. Dose-adjusted trough blood concentration (C/D ratio) was calculated. Polymerase chain reaction restriction fragment length polymorphism followed by sequencing was done for genotyping of CYP3A5*3 (6986A > G). RESULTS: At 1 week, 1 and 3 months C/D ratio were significantly lower in CYP3A5 expressers *1/*1 patients compared to non expressers *3/*3. CONCLUSION: CYP3A5 (6986A > G) genotype, rather than MDR-1 (2677G > A/T) variant, has an impact on tacrolimus pharmacokinetics. PMID- 26856711 TI - Primary peritonitis by Streptococcus pyogenes. A condition as rare as it is aggressive. AB - We report the case of a 60-year-old female patient who presented to the emergency room for abdominal pain standing with impaired general status, fever of up to 38.7oC, and somnolence. Upon arrival the patient had a heart rate of 115 bpm, hypotension (80/40 mmHg),acute respiratory distress, and both hepatic and renal failure. During her examination the patient was drowsy and had a diffusely tender abdomen with peritoneal irritation signs. Blood tests revealed 22,000 WBCs (82%N), CRP 32.4 mg/dL, total bilirubin 3.2 mg/dL, GOT 300 U/L, GPT 160 U/L, LDH 200 U/L, AP 310 U/L, 91,000 platelets, creatinine2.3 mg/dL, and PA 64%. An abdominal CT scan was performed, which revealed a minimal amount of free intraperitoneal fluid with no other findings. Given the patient's poor status an exploratory laparoscopy was carried out, which found a moderate amount of diffuse purulent exudate, particularly in interloop and lesser pelvis areas, with no additional findings. Following surgery she was transferred to the intensive care unit on wide spectrum antibiotics .Peritoneal exudate cultures from the surgical procedure revealed Streptococcus pyogenes. The patient had a favorable outcome being subsequently discharged from hospital at day 10 after the procedure. S. pyogenesis a beta hemolytic streptococcus well known as a cause of pharyngotonsillar, skin and soft tissues infection. Primary peritonitis by S.pyogenesis a rare condition with only a few isolated cases reported. PP cases by S.pyogenes predominantly involve previously healthy young women. PP diagnosis is usually retrospective, when other causes have been ruled out by surgery and culture is positive post hoc. An appropriate differential diagnosis from conditions such as gram-negative shock, staphylococcal toxic shock, meningococcal disease, viral infection, etc., is crucial. Abdominal CT may be helpful but a variable amount of free intraperitoneal fluid is usually the only finding. The surgical approach is usually laparoscopy in experienced sites. Attentive monitoring at an intensive care unit and adequate antibiotic therapy are key in association with surgery. There is no clear consensus on the antibiotics to be used for severe infection with S.pyogenes; empirical amoxicillin-clavulanic is usually the initial choice, followed after microbiological confirmation by clindamycin and a third-generation cephalosporin. PMID- 26856712 TI - Isolation of Propionibacterium acnes among the microbiota of primary endodontic infections with and without intraoral communication. AB - OBJECTIVES: The presence of opportunistic pathogens such as Propionibacterium acnes (P. acnes) may contribute to the endodontic pathology. The presence of P. acnes may be influenced by different endodontic conditions. The aims of the study were firstly, to identify P. acnes within the whole cultivable microbiota of primary endodontic infections, to investigate which P. acnes phylotypes predominate in such infections and secondly to determine if the presence of an "open" communication (e.g. a sinus) can be associated with the isolation of P. acnes from the root canal. MATERIAL AND METHODS: The predominant cultivable microbiota of 15 primary endodontic lesions (7 without communication with the oral environment and 8 with an open communication) were identified using partial 16S ribosomal RNA (rRNA) gene sequence analysis. The identification of the organism was determined by interrogating the Human Oral Microbiome Database. The P. acnes isolates were typed on the basis of the recA gene sequence comparison. A neighbor-joining tree was constructed using MEGA 4.1 with the inclusion of known recA sequences. RESULTS: There was no difference in the number of species identified from lesions without communication (5.86 +/- 3.7) and those with communication (5.37 +/- 3.6) (P > 0.05). PCR-based 16S rRNA gene sequencing revealed P. acnes as the most prevalent isolate recovered from lesions with communication. recA gene sequencing revealed two phylogenetic lineages present in lesion with communication, with mainly type I (further split into type IA and type IB) and type II. CONCLUSIONS: The presence of P. acnes as opportunistic pathogens has been confirmed and may sustain the traits observed in specific clinical presentations. CLINICAL RELEVANCE: Clinical management of open lesions may require further disinfection to eliminate opportunistic bacteria. PMID- 26856715 TI - The Brassica-derived phytochemical indolo[3,2-b]carbazole protects against oxidative DNA damage by aryl hydrocarbon receptor activation. AB - Epidemiological studies suggest that a high intake of Brassica vegetables protects against colon carcinogenesis. Brassica vegetables are rich in glucosinolates which are hydrolysed during digestion to various products including indole-3-carbinol. In animal studies, a protective effect of indole-3 carbinol has been demonstrated in colon carcinogenesis. Indole-3-carbinol is highly unstable and, therefore, the observed protection likely results from condensation products of indole-3-carbinol, e.g. diindolylmethane or indolo[3,2 b]carbazole (ICZ). Interestingly, ICZ is a potent activator of the aryl hydrocarbon receptor (AhR), a transcription factor known to mediate toxic effects of environmental pollutants, such as dioxin and polycyclic aromatic hydrocarbons. Here, we show that ICZ protects against oxidative DNA damage in various cell lines including the colon carcinoma cell line Caco-2. When preincubated for 24 h, ICZ decreases DNA single-strand break (SSB) and 8-oxo-dG formation induced by tertiary-butylhydroperoxide (t-BOOH), hydrogen peroxide or benzo[a]pyrene. Simultaneous addition of ICZ does not protect against t-BOOH-induced SSB formation, which disproves a direct radical scavenging effect. The repair of SSBs was not enhanced, but the data indicate that ICZ attenuates the ROS level following t-BOOH. The antioxidant response factor Nrf2 was not activated following ICZ. Functional inhibition of the AhR and AhR-/ARNT-defective cell lines demonstrate that the AhR/ARNT pathway is mandatory for the observed ROS defence caused by ICZ, supporting the hypothesis that AhR-mediated regulation of defence genes is involved. The data point to a hitherto unknown protective function of ICZ and a novel role of the AhR in the defence against oxidative DNA damage. PMID- 26856714 TI - Genotoxic properties of XLR-11, a widely consumed synthetic cannabinoid, and of the benzoyl indole RCS-4. AB - Aim of this study was the investigation of the genotoxic properties of XLR-11 [1 (5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone, a widely consumed synthetic cannabinoid (SC), and of the benzoyl indole RCS-4 (4 methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone). We characterized the DNA damaging properties of these drugs in different experimental systems. No evidence for induction of gene mutations was detected in bacterial (Salmonella/microsome) tests, but clear dose-dependent effects were found in in vitro single cell gel electrophoresis (SCGE) assays with human lymphocytes and with buccal- and lung derived human cell lines (TR-146 and A-549). These experiments are based on the determination of DNA migration in an electric field and enable the detection of single- and double-strand breaks and apurinic sites. Furthermore, we found that both drugs induce micronuclei which are formed as a consequence of chromosomal aberrations. The lack of effects in SCGE experiments with lesion-specific enzymes (FPG, Endo III) shows that the DNA damage is not caused by formation of oxidatively damaged bases; experiments with liver enzyme homogenates and bovine serum albumin indicate that the drugs are not converted enzymatically to DNA reactive intermediates. Furthermore, results with buccal- and lung-derived human cells show that gaseous treatment of the cells under conditions which reflect the exposure situation in drug users may cause damage of the genetic material in epithelia of the respiratory tract. Since DNA instability is involved in the etiology of cancer, these findings can be taken as an indication that consumption of the SCs may cause tumors in the respiratory tract of consumers. PMID- 26856716 TI - Adenovirus Hepatic Abscess: A Novel Source of Fever of Unknown Origin in a Pediatric Liver Transplant Recipient. PMID- 26856718 TI - Facilitating Minority Medical Education, Research, and Faculty. PMID- 26856719 TI - Conditional Survival as a Patient Centered Metric for Patients with Appendiceal Adenocarcinoma. AB - BACKGROUND: Prognosis of appendiceal adenocarcinoma patients is based on burden of disease, histology, and nature of therapy, which remains static despite time in follow-up. We hypothesized that conditional survival provides an informative metric that allows patients better understanding of their disease. METHODS: Using the Surveillance, Epidemiology and End Results database, patients with appendiceal adenocarcinoma from 1988 to 2012 were included. Actuarial Life table analyses and Kaplan-Meier curves were used for statistical inference. RESULTS: Of 5,952 patients, the median age was 60 years (IQR 50-72) and 52 % were female. Histologies included were adenocarcinoma (NOS 37 %), mucinous adenocarcinoma (MA 53 %), and signet ring cell (SRC 10 %). Five-year overall survival (OS) at diagnosis for patients with metastatic disease was 11 % (NOS), 45 % (MA), and 8 % (SRC), respectively. Annual conditional probability of survival from years 1-5 after diagnosis for patients with SRC with metastatic disease was 55, 60, 68, 55, and 82 % compared with 84, 86, 86, 88, and 92 % with MA. Probability of surviving the first year after extended surgery was 77 % (NOS), 85 % (MA), and 75 % (SRC). Those that survived 5 years after surgery had a 94 % (NOS), 93 % (MA), and 86 % (SRC) probability of surviving the sixth year. CONCLUSIONS: In the setting of dismal cumulative probability of survival (or overall survival), conditional probability is more informative in providing prognostication. This distinction might be important for patients especially with SRC who may live in constant fear of disease. Such data can be used to reassure patients and perhaps modify surveillance strategies for patients. PMID- 26856720 TI - Oncologic Outcomes of Extended Robotic Resection for Rectal Cancer. AB - BACKGROUND: Surgery for locally advanced rectal cancers beyond the plane of total mesorectal excision (TME) or extramesorectal nodal involvement should include complete resection. This study evaluated the oncologic feasibility and safety of robot-assisted surgery for rectal cancer beyond the TME plane. METHODS: The study analyzed the operative, perioperative, and oncologic outcomes for all patients who underwent robot-assisted extended rectal cancer surgery from April 2009 to February 2015. RESULTS: Of 36 patients, 22 underwent multivisceral en bloc resection, and 18 underwent extramesorectal lymph node (EMRLN) dissection. The median tumor location was 5 cm [interquartile range (IQR), 2.2-9.0 cm] from the anal verge. A total of 32 patients underwent neoadjuvant chemoradiation therapy. The median body mass index of the patients was 26.8 kg/m(2) (IQR, 24.0-31.9 kg/m(2)). Conversion was required for one patient because of inability to tolerate the Trendelenburg position. All the resections were R0, and there were no incomplete TMEs. The vagina and prostate or periprostatic structures were the most commonly resected (n = 13/22), and the lateral pelvic nodes were the most common EMRLNs (n = 16/18). The median numbers of examined mesorectal lymph nodes and EMRLNs were respectively 20 (IQR, 18.0-28.0) and 2.5 (IQR, 1.0-6.0). The median hospital stay was 4 days (IQR, 3.0-5.5 days). Six patients experienced Clavien-Dindo grade 3 complications, the most common of which was deep abscess (n = 5, 13.8 %). The 5-year actuarial local recurrence rate was 3.6 %. CONCLUSIONS: Minimally invasive resection for rectal cancer can be performed with extended lymph node dissection or en bloc multivisceral resection using the surgical robot in selected patients. This technique is feasible and has acceptable morbidity. PMID- 26856717 TI - Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease. AB - Nonalcoholic fatty liver disease (NAFLD) is a liver manifestation of metabolic syndrome. Overconsumption of high-fat diet (HFD) and increased intake of sugar sweetened beverages are major risk factors for development of NAFLD. Today the most commonly consumed sugar is high fructose corn syrup. Hepatic lipids may be derived from dietary intake, esterification of plasma free fatty acids (FFA) or hepatic de novo lipogenesis (DNL). A central abnormality in NAFLD is enhanced DNL. Hepatic DNL is increased in individuals with NAFLD, while the contribution of dietary fat and plasma FFA to hepatic lipids is not significantly altered. The importance of DNL in NAFLD is further established in mouse studies with knockout of genes involved in this process. Dietary fructose increases levels of enzymes involved in DNL even more strongly than HFD. Several properties of fructose metabolism make it particularly lipogenic. Fructose is absorbed via portal vein and delivered to the liver in much higher concentrations as compared to other tissues. Fructose increases protein levels of all DNL enzymes during its conversion into triglycerides. Additionally, fructose supports lipogenesis in the setting of insulin resistance as fructose does not require insulin for its metabolism, and it directly stimulates SREBP1c, a major transcriptional regulator of DNL. Fructose also leads to ATP depletion and suppression of mitochondrial fatty acid oxidation, resulting in increased production of reactive oxygen species. Furthermore, fructose promotes ER stress and uric acid formation, additional insulin independent pathways leading to DNL. In summary, fructose metabolism supports DNL more strongly than HFD and hepatic DNL is a central abnormality in NAFLD. Disrupting fructose metabolism in the liver may provide a new therapeutic option for the treatment of NAFLD. PMID- 26856721 TI - The Risk of Contralateral Non-sentinel Metastasis in Patients with Primary Vulvar Cancer and Unilaterally Positive Sentinel Node. AB - BACKGROUND: In patients with primary vulvar cancer and bilateral sentinel lymph node (SLN) biopsy, bilateral complete inguino-femoral lymphadenectomy (LAE) is recommended, even in cases with only unilaterally positive SLN by most guidelines. The risk of contralateral non-SLN metastasis is unclear. METHODS: All patients with primary vulvar cancer receiving an SLN dissection with radioactive tracer +/- blue dye at the University Medical Center Hamburg-Eppendorf between 2001 and 2013 were retrospectively evaluated. Median follow-up was 33 months. RESULTS: A total of 140 patients were included; 124 with bilateral and 16 with unilateral SLN dissection. A median number of two SLNs (range 1-7) per groin were dissected. Overall, 53 (53/140, 37.9 %) patients received a complete inguino femoral LAE, 41 of whom (77.4 %) had previously presented with a positive SLN (33 unilaterally, 8 bilaterally). Of the 33 patients with unilaterally positive SLN, 28 (84.9 %) underwent complete bilateral inguino-femoral LAE despite a contralateral negative SLN. Of these patients, none presented a contralateral non SLN metastasis (0/28, 0 %) in full dissection; however, one developed groin recurrence in the initially SLN-negative, fully dissected groin after 19 months (1/28, 3.6 %). CONCLUSION: In case of bilateral SLN biopsy for clinically node negative disease and only unilaterally positive SLN, the risk for contralateral non-SLN metastases appears to be low. These data support the omission of contralateral LAE to reduce surgical morbidity. PMID- 26856722 TI - Prognostic Impact of Para-Aortic Lymph Node Micrometastasis in Pancreatic Ductal Adenocarcinoma. AB - BACKGROUND: It is still unclear whether micrometastasis of para-aortic lymph nodes (PALNs) in pancreatic ductal adenocarcinoma (PDAC) is tantamount to PALN metastasis detected by hematoxylin and eosin (HE) staining. METHODS: A total of 242 patients with PDAC who underwent radical pancreatectomy with PALN dissection were eligible for this study. Micrometastasis in PALNs was evaluated by CAM 5.2 immunohistochemistry. The relationship between PALN status and overall survival (OS) was analyzed. RESULTS: Of the 242 enrolled patients, 25 (10 %) had PALN metastasis detected by HE (PALN HE-positive), and 21 (9 %) had PALN micrometastasis not detected by HE but identified by CAM 5.2 immunohistochemistry. Univariate analysis revealed that patients with PALN micrometastasis (p = .004) and PALN HE positivity (p = .003) had a significantly shorter OS than those without PALN metastasis, whereas no significant difference was observed between the two former groups (p = .874). In multivariate analysis, lack of adjuvant chemotherapy (hazard ratio [HR] 2.43, p < .001), PALN micrometastasis (HR 1.89; p = .046), and PALN HE-positivity (HR 1.89, p = .023) were identified as independent risk factors for poor prognosis. Within a subset of 46 patients with PALN HE-positivity or micrometastasis, lack of adjuvant chemotherapy was independently associated with poor OS (HR 2.58. p = .029). CONCLUSIONS: The prognosis of patients with PALN micrometastasis was extremely poor as well as HE-positive PALNs. However, postoperative adjuvant chemotherapy may contribute to improving the prognosis of PDAC patients with PALN metastasis. PMID- 26856723 TI - Colorectal Specialization Increases Lymph Node Yield: Evidence from a National Database. AB - BACKGROUND: Current guidelines recommend the evaluation of at least 12 lymph nodes (LNs) in the pathologic specimen following surgery for colorectal cancer (CRC). We sought to examine the role of colorectal specialization on nodal identification. METHODS: We conducted a retrospective cohort study using SEER Medicare data to examine the association between colorectal specialization and LN identification following surgery for colon and rectal adenocarcinoma between 2001 and 2009. Our dataset included patients >65 years who underwent surgical resection for CRC. We excluded patients with rectal cancer who had received neoadjuvant therapy. The primary outcome measure was the number of LNs identified in the pathologic specimen following surgery for CRC. Multivariate analysis was used to identify the association between surgical specialization and LN identification in the pathologic specimen. RESULTS: In multivariate analysis, odds of an adequate lymphadenectomy following surgery with a colorectal specialist were 1.32 and 1.41 times greater for colon and rectal cancer, respectively, than following surgery by a general surgeon (p < 0.001). These odds increased to 1.36 and 1.58, respectively, when analysis was limited to board certified colorectal surgeons. Hospital factors associated with >=12 LNs identified included high-volume CRC surgery (colon OR 1.84, p < 0.001; rectal OR 1.78, p < 0.001) and NCI-designated Cancer Centers (colon OR 1.75, p < 0.001; rectal OR 1.64; p = 0.007). CONCLUSIONS: Colorectal specialization and, in particular, board-certification in colorectal surgery, is significantly associated with increased LN identification following surgery for colon and rectal adenocarcinoma since the adoption of the 12-LN guideline in 2001. PMID- 26856725 TI - A Unified Approach to Functional Principal Component Analysis and Functional Multiple-Set Canonical Correlation. AB - Functional principal component analysis (FPCA) and functional multiple-set canonical correlation analysis (FMCCA) are data reduction techniques for functional data that are collected in the form of smooth curves or functions over a continuum such as time or space. In FPCA, low-dimensional components are extracted from a single functional dataset such that they explain the most variance of the dataset, whereas in FMCCA, low-dimensional components are obtained from each of multiple functional datasets in such a way that the associations among the components are maximized across the different sets. In this paper, we propose a unified approach to FPCA and FMCCA. The proposed approach subsumes both techniques as special cases. Furthermore, it permits a compromise between the techniques, such that components are obtained from each set of functional data to maximize their associations across different datasets, while accounting for the variance of the data well. We propose a single optimization criterion for the proposed approach, and develop an alternating regularized least squares algorithm to minimize the criterion in combination with basis function approximations to functions. We conduct a simulation study to investigate the performance of the proposed approach based on synthetic data. We also apply the approach for the analysis of multiple-subject functional magnetic resonance imaging data to obtain low-dimensional components of blood-oxygen level dependent signal changes of the brain over time, which are highly correlated across the subjects as well as representative of the data. The extracted components are used to identify networks of neural activity that are commonly activated across the subjects while carrying out a working memory task. PMID- 26856724 TI - The impact of chronic intermittent hypoxia on hematopoiesis and the bone marrow microenvironment. AB - Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder which is associated with patient morbidity and an elevated risk of developing hypertension and cardiovascular diseases. There is ample evidence for the involvement of bone marrow (BM) cells in the pathophysiology of cardiovascular diseases but a connection between OSA and modulation of the BM microenvironment had not been established. Here, we studied how chronic intermittent hypoxia (CIH) affected hematopoiesis and the BM microenvironment, in a rat model of OSA. We show that CIH followed by normoxia increases the bone marrow hypoxic area, increases the number of multipotent hematopoietic progenitors (CFU assay), promotes erythropoiesis, and increases monocyte counts. In the BM microenvironment of CIH-subjected animals, the number of VE-cadherin expressing blood vessels, particularly sinusoids, increased, accompanied by increased smooth muscle cell coverage, while vWF-positive vessels decreased. Molecularly, we investigated the expression of endothelial cell-derived genes (angiocrine factors) that could explain the cellular phenotypes. Accordingly, we observed an increase in colony-stimulating factor 1, vascular endothelium growth factor, delta-like 4, and angiopoietin-1 expression. Our data shows that CIH induces vascular remodeling in the BM microenvironment, which modulates hematopoiesis, increasing erythropoiesis, and circulating monocytes. Our study reveals for the first time the effect of CIH in hematopoiesis and suggests that hematopoietic changes may occur in OSA patients. PMID- 26856726 TI - Cross-cultural adaptation and validation of the Portuguese version of "The assessment of knowledge in ankylosing spondylitis patients by a self-administered questionnaire". AB - Knowledge is an important factor in patients with ankylosing spondylitis regarding the adoption of appropriate behaviours and education. The aim of this study was to culturally adapt and validate "The assessment of knowledge in ankylosing spondylitis patients by a self-administered questionnaire" for the Portuguese population with ankylosing spondylitis. The Portuguese version of "The assessment of knowledge in ankylosing spondylitis patients by a self-administered questionnaire" was administered to a sample of 180 subjects, from which 63 individuals responded. The adaptation process involved translation, back translation and submission to a committee of experts in the area, culminating with a Portuguese version of the instrument. Next, the scale reliability and validity were assessed. There was a statistically significant decrease from test to retest, although the intra-class correlation coefficient between test and retest was 0.76 (95 % CI 0.61-0.86), which was considered good. From 180 individuals, 63 (35.0 %) subjects were available for the present study. The proportion of individuals that correctly answered each item ranged from 19 to 92 %, corresponding to items 8 and 13, respectively. The mean number of correct answers was 8.5 [mean (SD) = 2.4] in 12 questions. The proposed Portuguese version of the ankylosing spondylitis knowledge scale showed good reliability, reproducibility and construct validity. PMID- 26856727 TI - Spinal cord stimulation improves forelimb use in an alpha-synuclein animal model of Parkinson's disease. AB - Neuromodulation by spinal cord stimulation has been proposed as a symptomatic treatment for Parkinson's disease. We tested the chronic effects of spinal cord stimulation in a progressive model of Parkinson's based on overexpression of alpha-synuclein in the substantia nigra. Adult Sprague Dawley rats received unilateral injections of adeno-associated virus serotype 6 (AAV6) in the substantia nigra to express alpha-synuclein. Locomotion and forepaw use of the rats were evaluated during the next 10 weeks. Starting on week 6, a group of AAV6 injected rats received spinal cord stimulation once a week. At the end of the experiment, tyrosine hydroxylase and alpha-synuclein immunostaining were performed. Rats with unilateral alpha-synuclein expression showed a significant decrease in the use of the contralateral forepaw, which was mildly but significantly reverted by spinal cord stimulation applied once a week from the 6th to the 10th week after the AAV6 injection. Long-term spinal cord stimulation proved to be effective to suppress or delay motor symptoms in a sustained and progressive model of Parkinson's and might become an alternative, less invasive neuromodulation option to treat this disease. PMID- 26856730 TI - Facile preparation of free-standing rGO paper-based Ni-Mn LDH/graphene superlattice composites as a pseudocapacitive electrode. AB - A novel film electrode was assembled via a simple filtration process, with an rGO paper as the substrate and Ni-Mn LDH/graphene superlattice composites as the functional layer. The electrode presented typical pseudocapacitive behaviours with excellent rate property and cycle stability. PMID- 26856728 TI - Psychological impact of lymphoma on adolescents and young adults: not a matter of black or white. AB - PURPOSE: The purpose of the study is to examine differences in perceived impact of cancer (IOC) between adolescents and young adults (AYAs; 18-35 years at cancer diagnosis), adults (36-64 years) and elderly (65-84 years) with a history of (non )Hodgkin lymphoma. Furthermore, to investigate the association of socio demographic, clinical and psychological characteristics with IOC; and the association between IOC and health-related quality of life (HRQoL) among AYAs only. METHODS: This study is part of a population-based PROFILES registry survey among lymphoma patients diagnosed between 1999 and 2009. Patients (n = 1.281) were invited to complete the IOCv1 and EORTC-QLQ-C30 questionnaires. Response rate was 67 % (n = 861). RESULTS: AYA lymphoma survivors scored higher on the positive IOC summary scale, compared to adult and elderly patients (p < 0.001), while no significant differences were observed for negative IOC. Among AYAs, females, survivors with a partner, and survivors with elevated psychological distress levels scored significantly higher on the negative IOC summary scale. The negative IOC summary scale was negatively associated with all EORTC QLQ-C30 functioning scales (beta ranging from -0.39 to -0.063; p < 0.05). The positive IOC summary scale was negatively associated with the EORTC QLQ-C30 subscale 'Emotional functioning' (beta = -0.24; p < 0.05). CONCLUSION: AYA, adult and elderly with a history of (non-)Hodgkin lymphoma experienced different types of IOC in terms of positive and negative aspects. IMPLICATIONS FOR CANCER SURVIVORS: Although AYAs experience a more positive IOC compared to older survivors, some AYAs experience more negative IOC and may require developmentally appropriate interventions to address their specific concerns. PMID- 26856729 TI - Cancer and frailty in older adults: a nested case-control study of the Mexican Health and Aging Study. AB - PURPOSE: Understanding how the convergence between chronic and complex diseases such as cancer-and emerging conditions of older adults-such as frailty-takes place would help in halting the path that leads to disability in this age group. The objective of this manuscript is to describe the association between a past medical history of cancer and frailty in Mexican older adults. METHODS: This is a nested in cohort case-control study of the Mexican Health and Aging Study. Frailty was categorized by developing a 55-item frailty index that was also used to define cases in two ways: incident frailty (incident >0.25 frailty index score) and worsening frailty (negative residuals from a regression between 2001 and 2012 frailty index scores). Exposition was defined as self-report of cancer between 2001 and 2012. Older adults with a cancer history were further divided into recently diagnosed (<10 years) and remotely diagnosed (>10 years from the initial diagnosis). Odds ratios were estimated by fitting a logistic regression adjusted for confounding variables. RESULTS: Out of a total of 8022 older adults with a mean age of 70.6 years, the prevalence of a past medical history of cancer was 3.6 % (n = 288). Among these participants, 45.1 % had been diagnosed with cancer more than 10 years previously. A higher risk of incident frailty compared to controls [odds ratio (OR) 1.53 (95 % confidence interval (CI) 1.04-2.26, p = 0.03); adjusted model OR 1.74 (95 % CI 1.15-2.61, p = 0.008)] was found in the group with a recent cancer diagnosis. Also, an inverse association between a remote cancer diagnosis and worsening frailty was found [OR = 0.56 (95 % CI 0.39 0.8), p = 0.002; adjusted model OR 0.61 (95 % CI 0.38-0.99, p = 0.046)]. CONCLUSIONS: Cancer is associated with a higher frailty index, with a potential relevant role of the time that has elapsed since the cancer diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors may be more likely to develop frailty or worsening of the health status at an older age. This relationship seems especially evident among individuals with a recent oncological diagnosis. Health professionals in charge of older adult care should be aware of this association in order to improve outcomes of older adults who survived cancer. PMID- 26856731 TI - Neonatal Sepsis Presenting as Pyocele. PMID- 26856732 TI - Decreased Anemia Prevalence Among Women and Children in Rural Baja California, Mexico: A 6-Year Comparative Study. AB - Anemia is a public health problem in Mexico. This study sought to determine the prevalence and correlates of anemia among women and children residing in a rural farming region of Baja California, Mexico. An existing partnership between universities, non-governmental organizations, and an underserved Mexican community was utilized to perform cross-sectional data collection in 2004-2005 (Wave 1) and in 2011-2012 (Wave 2) among women (15-49 years) and their children (6-59 months). All participants completed a survey and underwent anemia testing. Blood smears were obtained to identify etiology. Nutrition education interventions and clinical health evaluations were offered between waves. Participants included 201 women and 99 children in Wave 1, and 146 women and 77 children in Wave 2. Prevalence of anemia significantly decreased from 42.3 to 23.3 % between Waves 1 and 2 in women (p < 0.001), from 46.5 to 30.2 % in children 24-59 months (p = 0.066), and from 71.4 to 45.8 % in children 6-23 months (p = 0.061). Among women in Wave 1, consumption of iron absorption enhancing foods (green vegetables and fruits high in vitamin C) was protective against anemia (p = 0.043). Women in Wave 2 who ate >=4 servings of green, leafy vegetables per week were less likely to be anemic (p = 0.034). Microscopic examination of blood smears revealed microcytic, hypochromic red blood cells in 90 % of anemic children and 68.8 % of anemic women, consistent with iron deficiency anemia. PMID- 26856734 TI - Prostatic specific antigen. From its early days until becoming a prostate cancer biomarker. AB - Prostate-specific antigen (PSA) has been since the mid 80's the most commonly used biomarker for measuring current and future risk of prostate cancer, for its early detection and to measure response to treatments and detecting recurrence in all stages of the disease. PSA's early development came along with progress in the field of immunology, which allowed detection and study of antigens from different tissues and fluids when injecting them into rabbits to promote immune response. Rubin Flocks in 1960 was the first to investigate and discover prostate specific antigens in benign and malignant tissue. Some years later, Hara, a Japanese forensic investigator, found 'gamma seminoprotein', that he used to detect human semen in rape cases. However, his work published in Japanese did not reach the Englishspeaking scientific community. In 1970 Ablin discovered both in prostatic fluid and tissue what he called "prostate-specific antigen", but he didn't characterize or describe it. Investigators Li and Beling, and Sensabaugh, approached the current PSA, but they were limited by available technology at that time. Dr T Ming Chu led a research team on prostate cancer in New York, USA and published their results in 1979. He finally received the patent for the discovery of "human purified prostate antigen" in 1984. Due to this work, the Food and Drug Administration (FDA), in USA, approved the use of PSA for monitoring recurrence after treatment. It was later known that PSA was not prostate-specific since it was produced in other tissues and fluids, but it was recognized that it was human species-specific. Works by Papsidero and Stamey showed new indications and utilities for PSA, but it was Catalona who first used it as a marker for prostate cancer in 1991. Thanks to these advances FDA authorized in 1994 the clinical use of PSA for early detection of prostate cancer. PMID- 26856733 TI - The Role of Health Literacy in Reducing Negative Perceptions of Breast Health and Treatment Among Uninsured Primary Care Patients. AB - Breast cancer is the second leading cause of cancer death among women in the United States. There are disparities in breast cancer mortality by race/ethnicity and socio-economic factors. Health literacy may have an impact on breast health disparities. In addition, learning about people's perceptions of breast health and treatment is important to understand why some do not seek a mammogram or treatment for breast cancer. The purpose of this study is to examine the association between health literacy and negative perceptions of breast health and treatment among female uninsured primary care patients utilizing a free clinic for underserved populations. Women utilizing a free clinic who were aged 40 years or older (N = 276) participated in a self-administered survey from September to December in 2015. Higher levels of health literacy were associated with lower levels of negative perceptions of breast cancer and treatment. Non-US born English speakers reported higher levels of negative perceptions of breast cancer and treatment than US born English speakers and Spanish speakers. While there were no significant differences in health literacy among the groups, US born English speakers were less likely to have had a mammogram in the past 3 years compared with non-US born English speakers and Spanish speakers. Future research should consider where women are obtaining information and how the method of exposure shapes their attitudes towards breast health and in turn, their rates of examinations for breast cancer. Cultural factors may be also important determinants of the perceptions and need to be further examined. PMID- 26856735 TI - Anastomic urethroplasty in bulbar urethral stricture. 13 years experience in a department of urology. AB - Urethral stenosis is a common disease in the clinical practice of urology, with a major impact on the quality of life of patients. The anastomotic urethroplasty is a technique with very precise indications usually membranous or bulbar urethra stenosis with a length of 3 cm or up to 7 cm when it is secondary to urethral disruptions (no stenosis) after pelvic trauma. OBJECTIVE: We review anastomotic urethroplasty performed in our department between 2002 and 2015. METHODS: A retrospective, descriptive and inferential analysis on 107 patients out of 482 treated with Anastomotic urethroplasty by urethral strictures at the Urology Department of the Hospital "Virgen de la Victoria" (Malaga) from January 2002 to September 2015, establishing effectiveness and safety of the technique, as well as factors that might influence the results. The main diagnostic method was retrograde urethrography and voiding cystourethrography in 100% of patients undergoing surgery, using voiding uroflowmetry for subsequent monitoring. The definition of success was a postoperative flowmetry with Qmax>15 ml/s, and in case of lower flow, we perform a cystoscopy to verify recurrence of stenosis or exclude other pathology. RESULTS: The median age was 42 years, with a mean follow up of 59 months. The length of stenosis valued by retrograde urethrography and voiding cystourethrography was in 91.6% of cases of >1 cm and <2 cm. The most common etiology was idiopathic in 72.9%, followed by iatrogenic with 15.9%. Regarding the location, it was observed that the area most often affected was the bulbar urethra with 82.2%, with the membranous urethra in second place. In 77.6% of patients anastomotic urethroplasty was the initial treatment, followed in frequency by direct vision internal urethrotomy 9.3%. In the case of comorbidities associated with treatment with anastomotic urethroplasty it was observed that only Diabetes Mellitus had a tendency to statistical significance, with p=0.092, not demonstrating such significance in the case of hypertension or when the subject presented Diabetes Mellitus together with hypertension. Finally, the intervention was successful in 102 cases (95.3%), with only 5 cases (4.7%) where it failed, 4 of them treated with a new Anastomotic urethroplasty, with resolution of the stricture. CONCLUSIONS: Anastomotic urethroplasty is the treatment of choice for short bulbar urethral stricture, with high success rate and low complication rate, as well as low recurrence of these. PMID- 26856737 TI - Diagnosis challenge of atypical spindle cells neoplasm of the spermatic cord. AB - OBJECTIVE: To report an unusual case of softtissue neoplasm and to review the literature on this type of tumour. METHODS: We report an accidentally found tumour closely related to the spermatic cord that was diagnosed in a 70 year-old man when he was being operated on for an inguinal hernia repair. RESULTS: After thorough analysis by experienced pathologists it was not possible to determine the nature of the tumour that was removed at surgery. CONCLUSIONS: Soft tissues neoplasms of the spermatic cord may occur in an unusual way and they may be a real challenge to diagnose. PMID- 26856736 TI - Influence of barbed suture in laparoscopic radical prostatectomy. AB - OBJECTIVES: To determine the influence of barbed suture in laparoscopic radical prostatectomy. METHODS: A retrospective study of 150 patients who underwent laparoscopic radical prostatectomy was carried out by our department. The patients were divided in two groups according to the kind of suture used during the vesicourethral anastomosis: conventional 3-0 absorbable multifilament running suture (group 1) and bidirectional barbed suture (Quill(r)) (group 2). Operating time, postoperatory urinary fistula, hospital stay and catheter duration were analyzed in both groups. RESULTS: After the analysis of all the preoperative variables, such as age, PSA, prostate volume, Gleason and stage on biopsy, no statistically significant differences were found in both groups. Operating time was significantly shorter in Group 2 (169+/-43 min vs 215+/-45 min, p=0.00). Statistically significant differences were found regarding postoperative urinary fistula rate, hospital stay and urethral catheterization duration, favourable to Group 2. CONCLUSIONS: The use of bidirectional barbed suture (Quill(r)) for vesicourethral anastomosis in laparoscopic radical prostatectomy, when compared with the conventional suture, shortens surgical time, reduces urinary fistula rate, catheter duration and hospital stay, as the anastomosis is easily performed and prevents leakage. PMID- 26856738 TI - Treatment with hydrochlorothiazide and alendronate in patients with stones and bone mineral density loss. Evolution of bone metabolism and calciuria with medical treatment. AB - OBJECTIVES: Treatment of calcium stones is based on diet and pharmacological measures such as the use of thiazides and other drugs. The aim of this study is to assess the effect of alendronate on hydrochlorothiazide on urinary calcium and bone mineral density in patients with calcium stones. METHODS: Prospective observational study involving 77 patients with relapsing calcium stones divided into 2 groups according to treatment received. Group 1: 36 patients treated with alendronate 70 mg/week; Group 2: 41 patients treated with hydrochlorothiazide 50 mg/day. All patients receive diet recommendations and fluid intake. Studied and analyzed among other variables were bone mineral density, bone turnover markers and calciuria before and after 2 years of treatment. Statistical study with SPSS 17.0, statistical significance p<0.05. RESULTS: No statistically significant differences in the distribution by sex or age of the patients between groups. In group 1 statistically a significant decrease was observed in the Beta-crosslaps and improvement in bone mineral density, along with decreased urinary calcium after 2 years of treatment. In Group 2 statistically significant decrease in urinary calcium and fasting calcium/creatinine was seen, along with improvement in bone mineral density after 2 years of treatment. In group 1, there is a more obvious and significant improvement in bone mineral density compared to 2 and Beta-crosslaps decrease. However, in group 2 the decrease in urinary calcium and calcium/creatinine was more significant than in group 1. CONCLUSION: Treatment with thiazide decrease calciuria and produces an improvement in bone mineral density, although not in the same range as treatment with alendronate. PMID- 26856741 TI - Haematological cancer: Send in the decoys, STAT! PMID- 26856740 TI - Automated single cell isolation from suspension with computer vision. AB - Current robots can manipulate only surface-attached cells seriously limiting the fields of their application for single cell handling. We developed a computer vision-based robot applying a motorized microscope and micropipette to recognize and gently isolate intact individual cells for subsequent analysis, e.g., DNA/RNA sequencing in 1-2 nanoliters from a thin (~100 MUm) layer of cell suspension. It can retrieve rare cells, needs minimal sample preparation, and can be applied for virtually any tissue cell type. Combination of 1 MUm positioning precision, adaptive cell targeting and below 1 nl liquid handling precision resulted in an unprecedented accuracy and efficiency in robotic single cell isolation. Single cells were injected either into the wells of a miniature plate with a sorting speed of 3 cells/min or into standard PCR tubes with 2 cells/min. We could isolate labeled cells also from dense cultures containing ~1,000 times more unlabeled cells by the successive application of the sorting process. We compared the efficiency of our method to that of single cell entrapment in microwells and subsequent sorting with the automated micropipette: the recovery rate of single cells was greatly improved. PMID- 26856743 TI - Haematological cancer: MRD assessment - guiding decisions for patients with AML. PMID- 26856742 TI - Health policy: Putting a price on cancer. PMID- 26856746 TI - Use of Prostate-Specific Antigen Testing Is in the Eye of the Beholder. PMID- 26856744 TI - Biomarkers of residual disease after neoadjuvant therapy for breast cancer. AB - Nowadays, the decision of which adjuvant treatment should be given to patients with residual breast cancer after neoadjuvant therapy is based on the initial, pretreatment breast cancer molecular subtype and on the estimated residual tumour burden after neoadjuvant therapy. Substantial biological differences exist, however, between treatment-naive breast cancer and the residual tissue that remains after neoadjuvant therapy. In addition, the evaluation of relapse risk in patients is subject to a lack of uniformity in pathological qualification and quantification of remnant breast cancer following neoadjuvant treatment. In this Review, we present the recent recommendations for standardized evaluation of response to neoadjuvant therapy in patients with breast cancer, followed by a comprehensive overview of the pathobiological features of the residual disease after neoadjuvant therapy, which could serve as prognostic biomarkers or guide the choice of targeted adjuvant approaches. These biomarker candidates are at different stages of development, but some already have demonstrated superior prognostic value compared with biomarkers derived from pretreatment breast-cancer characteristics. The evidence presented herein indicates that further research on the biology of breast cancer that persists after neoadjuvant therapy is necessary to improve the management of this disease. PMID- 26856747 TI - Is the Hype of Medical Marijuana All Smoke and Mirrors? AB - Being classified as a Schedule I drug by the Federal government has not prevented states from passing their own medical marijuana laws. While there is no denying that marijuana's euphoria makes people feel better, there is a lack of scientific data to support the efficacy of marijuana for gastrointestinal diseases. Marijuana, when used as a medical treatment, should be held to the same standards as any other drug coming to market including investigating the adverse event profile and ensuring a rigorous quality control program. Although we are not writing a prescription in the classic definition, we are signing state paperwork supporting the use as a treatment for a medical illness. Therefore, we have the obligation to our patients to ensure that we are recommending a safe and effective drug. More research needs to be conducted until we can reach that conclusion. PMID- 26856745 TI - Next-generation sequencing-based molecular diagnosis of 12 inherited retinal disease probands of Uyghur ethnicity. AB - Inherited retinal disease (IRD) is a category of genetic disorders affecting retina. Understanding the molecular basis of IRD is vital for clinical and genetic classification of patients. Uyghur people is an isolated ethnic group mainly residing in northwestern China with genetic admixture from Europeans and East Asians. The genetic etiology of IRD in this specific population still remains unknown. Here, by next-generation sequencing (NGS), we screened mutations in over 200 known retinal disease genes in a cohort of 12 unrelated Uyghur IRD probands. Out of the 12 probands, six are solved with high confidence, two with low confidence, while the remaining four are unsolved. We identified known disease-causing alleles in this cohort that suggest ancient Uyghur migration and also discovered eight novel disease-associated variants. Our results showed NGS based mutation screening as a reliable approach for molecular diagnosis. In addition, this approach can also be applied to reveal the genetic history of a specific ethnic group. PMID- 26856748 TI - Knowledge and Uptake of Genetic Counseling and Colonoscopic Screening Among Individuals at Increased Risk for Lynch Syndrome and their Endoscopists from the Family Health Promotion Project. AB - OBJECTIVES: Individuals whose families meet the Amsterdam II clinical criteria for hereditary non-polyposis colorectal cancer are recommended to be referred for genetic counseling and to have colonoscopic screening every 1-2 years. To assess the uptake and knowledge of guideline-based genetic counseling and colonoscopic screening in unaffected members of families who meet Amsterdam II criteria and their treating endoscopists. METHODS: Participants in the Family Health Promotion Project who met the Amsterdam II criteria were surveyed regarding their knowledge of risk-appropriate guidelines for genetic counseling and colonoscopy screening. Endoscopy/pathology reports were obtained from patients screened during the study to determine the follow-up recommendations made by their endoscopists. Survey responses were compared using Fisher's Exact and the chi(2) test. Concordance in participant/provider-reported surveillance interval was assessed using the kappa statistic. RESULTS: Of the 165 participants, the majority (98%) agreed that genetics and family history are important predictors of CRC, and 63% had heard of genetic testing for CRC, although only 31% reported being advised to undergo genetic counseling by their doctor, and only 7% had undergone genetic testing. Only 26% of participants reported that they thought they should have colonoscopy every 1-2 years and 30% of endoscopists for these participants recommended 1-2 year follow-up colonoscopy. There was a 65% concordance (weighted kappa 0.42, 95% CI 0.24-0.61) between endoscopist recommendations and participant reports regarding screening intervals. CONCLUSIONS: A minority of individuals meeting Amsterdam II criteria in this series have had genetic testing and reported accurate knowledge of risk-appropriate screening, and only a small percentage of their endoscopists provided them with the appropriate screening recommendations. There was moderate concordance between endoscopist recommendations and participant knowledge suggesting that future educational interventions need to target both health-care providers and their patients. PMID- 26856749 TI - Food: The Main Course to Wellness and Illness in Patients With Irritable Bowel Syndrome. AB - Food sits at the intersection between gastrointestinal (GI) physiology and symptoms in patients with the irritable bowel syndrome (IBS). It is now clear that the majority of IBS sufferers associate eating a meal with their GI and non GI symptoms. This is hardly surprising when one considers that food can affect a variety of physiologic factors (motility, visceral sensation, brain-gut interactions, microbiome, permeability, immune activation, and neuro-endocrine function) relevant to the pathogenesis of IBS. In recent years, clinical research has increasingly focused on diet as a treatment for IBS. There is a relative paucity of data from rigorous, randomized, controlled trials for any dietary intervention in IBS patients. Currently, the largest body of literature has addressed the efficacy of dietary restriction of fermentable oligo, di, monosaccharides, and polyols (FODMAPs). In the future, dietary treatments for IBS will move beyond the current focus on elimination to embrace supplementation with "functional" foods. PMID- 26856751 TI - The Elusive Bleeder: Tips for Avoiding a Wild Goose Chase. PMID- 26856750 TI - Characterizing Factors Associated With Differences in FGF19 Blood Levels and Synthesis in Patients With Primary Bile Acid Diarrhea. AB - OBJECTIVES: Chronic diarrhea caused by primary bile acid diarrhea (PBAD) is a common condition. We have previously shown PBAD is associated with low fasting serum levels of the ileal hormone, fibroblast growth factor 19 (FGF19). FGF19 is a negative regulator of hepatic bile acid synthesis and is stimulated by farnesoid X receptor agonists, which produce symptomatic improvement in PBAD. We aimed to assess possible causes for low serum FGF19 in patients with PBAD. METHODS: Patients with PBAD, defined by reduced (75)Se-labelled homocholic acid taurine (SeHCAT) retention, and idiopathic diarrhea controls had measurements of fasting lipids and fasting/post-prandial FGF19 serum profiles. Specific functional variants in candidate genes were investigated in exploratory studies. In further groups, basal and bile acid-stimulated transcript expression was determined in ileal biopsies and explant cultures by quantitative PCR. RESULTS: FGF19 profiles in PBAD patients included low fasting and meal-stimulated responses, which were both strongly correlated with SeHCAT. A subgroup of 30% of PBAD patients had fasting hypertriglyceridemia and higher FGF19. No clear significant differences were found for any genetic variant but there were borderline associations with FGFR4 and KLB. SeHCAT retention significantly correlated with the basal ileal transcript expression of FGF19 (rs=0.59, P=0.03) and apical sodium-dependent bile acid transporter (ASBT) (rs=0.49, P=0.04), and also with the degree of stimulation by chenodeoxycholic acid at 6 h for transcripts of FGF19 (median 184-fold, rs=0.50, P=0.02) and ileal bile acid binding protein (IBABP) (median 2.2-fold, rs=0.47, P=0.04). Median stimulation of FGF19 was lower in patients with SeHCAT retention <10% (P=0.01). CONCLUSIONS: These studies demonstrate a complex, multifactorial etiology of PBAD, including impairments in ileal FGF19 expression and responsiveness. PMID- 26856752 TI - Opening the Bird's Beak: Tips and Tricks for Effective Pneumatic Dilation for Achalasia. PMID- 26856754 TI - Systematic Review and Meta-Analysis: Infliximab or Cyclosporine as Rescue Therapy in Patients With Severe Ulcerative Colitis Refractory to Steroids. AB - OBJECTIVES: Acute severe steroid-refractory ulcerative colitis (UC) carries a poor prognosis and requires optimal management. A systematic review and meta analysis were conducted to assess cyclosporine and infliximab (IFX) as rescue agents in patients with steroid-refractory UC. METHODS: A literature search identified studies that investigated IFX and cyclosporine in steroid-refractory UC patients. The primary outcome was short-term response to treatment. Secondary outcomes included the rates of colectomy at 3 months and 12 months, adverse drug reactions, post-operative complications in those who received rescue therapy but underwent colectomy subsequently, and mortality. Odds ratios (ORs) with 95% confidence intervals (CIs) are reported. RESULTS: Overall, 16 studies with 1,473 participants were eligible for inclusion. Among three randomized controlled trials, no significant difference was seen with IFX compared with cyclosporine with regard to treatment response and 3- or 12-month colectomy. Among 13 non randomized studies, IFX was associated with significantly higher rates of treatment response (OR 2.96 (95% CI 2.12-4.14, chi(2)=6.50, I(2)=0%)) and a lower 12-month colectomy rate (OR 0.42 (95% CI 0.22-0.83, chi(2)=30.94, I(2)=71%)), with no significant difference seen in the 3-month colectomy rate (OR 0.53 (95% CI 0.22-1.28, chi(2)=22.73, I(2)=69%)) compared with cyclosporine. There were no significant differences between IFX and cyclosporine in adverse drug-related events, post-operative complications, or mortality. CONCLUSIONS: In the management of steroid-refractory severe UC, no definitive difference between IFX and cyclosporine is demonstrated by randomized trials, but non-randomized studies suggest that IFX is associated with better treatment response and lower risk of colectomy at 12 months. Prospective studies comparing dose-optimized IFX with cyclosporine are needed. PMID- 26856753 TI - Impact of Smoking Cessation on the Clinical Course of Crohn's Disease Under Current Therapeutic Algorithms: A Multicenter Prospective Study. AB - OBJECTIVES: Given the importance of tobacco smoking (TS) as the only environmental factor repeatedly linked to the development of the Crohn's disease (CD), it is surprising that very few prospective studies have assessed whether TS is associated with an increased frequency of clinical relapse. Our aim was to evaluate the current impact of TS on disease relapse and the clinical benefit of quitting smoking in the present era of widespread use of anti-TNF drugs and immunosuppressants. METHODS: This was a multicenter prospective cohort study, which included 573 CD patients in clinical remission with various smoking habits. All smokers were advised to quit. Patients not exposed to tobacco before inclusion (non- and former smokers), continuing smokers, and quitters were compared regarding differences in disease outcomes during a follow-up of 4 years. RESULTS: A total of 148 continuing smokers, 190 nonsmokers, 160 former smokers, and 75 quitters were included. In comparison with nonsmokers, continuing smokers relapsed more frequently with an incidence rate ratio of 1.53 (95% confidence interval (CI): 1.10-2.17). Former smokers and quitters had similar relapse incidences compared with nonsmokers. Smoking was an independent predictor for disease relapse in the multivariate analysis (hazard ratio: 1.58 (95% CI 1.20 2.09). In the time-dependent analysis, continuing smokers had earlier relapse, regardless of anti-TNF or immunosuppressant use. CONCLUSIONS: Continuing smokers have more disease relapses, and patients who quit smoking have a similar relapse incidence compared with nonsmokers. PMID- 26856755 TI - RNF135, RING finger protein, promotes the proliferation of human glioblastoma cells in vivo and in vitro via the ERK pathway. AB - Ring finger protein 135 (RNF135), located on chromosome 17q11.2, is a RING finger domain-containing E3 ubiquitin ligase that was identified as a bio-marker and therapy target of glioblastoma. In our study, we confirmed that RNF135 was up regulated in glioblastoma tissues compared with normal brain (NB) tissues, and that RNF135 knockdown inhibited proliferation and migration and led to cell cycle arrest in the G0/G1 phase in vivo. By lowering RNF135 expression, phosphorylated Erk and cell cycle protein CDK4 were down-regulated, while p27(Kip1) and p21(Waf1/Cip1) were up-regulated in U87 and U251 cells in vitro. In addition, using the immunofluorescence double labelling method, we found that RNF135 and P Erk were co-localized in the cytoplasm and were highly expressed in glioblastoma samples compared with NB tissues. Moreover, the growth of U87 cell-transplanted tumours in nude mice was inhibited while transduced with Lv-shRNF135. Taken together, our findings demonstrate the biological effects of RNF135 in glioblastoma cell proliferation, migration and cell cycle, and its role in the progression of glioblastoma may be associated with the ERK signal transduction pathway. PMID- 26856756 TI - Cerebral white matter lesions - associations with Abeta isoforms and amyloid PET. AB - Small vessel disease (SVD) and amyloid deposition may promote each other, with a potential association between SVD and altered production or clearance of beta amyloid (Abeta) affecting its cleavage products. We investigated the relationship between SVD, multiple isoforms of Abeta in cerebrospinal fluid (CSF) and cortical Abeta in 831 subjects with cognitive performance ranging from normal to Alzheimer's disease (AD) (the Swedish BioFINDER study). SVD was estimated as white matter lesions (WML) and lacunes. 18F-flutemetamol PET was performed in 321 subjects. Lower CSF levels of Abeta38 and Abeta40 were consistently associated with increased WML in all subgroups, while lower levels of CSF Abeta42 were associated with WML mainly in AD. CSF Abeta38 and Abeta40 were associated with regional WML in all regions, while CSF Abeta42 was associated with temporal WML only. A composite measure of 18F-flutemetamol uptake was not associated with WML, and regional 18F-flutemetamol uptake only with temporal WML. Lacunes were not associated with Abeta isoforms nor 18F-flutemetamol uptake. Our results suggest that WML may be associated with alterations in the production or clearance of Abeta species, particularly of Abeta38 and Abeta40. However, in AD cases, Abeta42 pathology might be associated with WML, especially in the temporal lobe. PMID- 26856757 TI - Seasonal Variability in Spider Assemblages in Traditional and Transgenic Rice Fields. AB - The use of Bt transgenic rice (or Bt rice) remains controversial in several countries, including China. Risk assessments are a prerequisite to confirm the safety of Bt rice for ecosystems before a commercial release. This study was conducted to compare the responses of spider assemblages to Bt rice and nontransgenic rice. Two experiments with different locations and times were conducted, and the data were analyzed using standard diversity indices and multivariate community analysis. With both analytical approaches, spider diversity and assemblage composition were not significantly different between Bt and non transgenic rice fields. However, based on principal component analyses, temporal (seasonal) variations occurred in the composition of the spider assemblage. In this study, Bt rice had no detrimental effects on the spider assemblages, although assemblage composition and species abundance varied during the growing season. This study demonstrated an advantage in using community assemblages and repeated sampling to compare fields over a growing season because changes in the assemblages, and more specifically for some species, not always the most dominant, may vary over time. To more accurately assess the changes in composition and structure of spider assemblages through time, particularly for those species that may require a longer period to detect a response, an increase in sampling effort and longer-term experiments might be required. PMID- 26856759 TI - Treatment of Meniscal Tear: The More We Learn, the Less We Know. PMID- 26856758 TI - Psychometric Properties of the Persian Translation of the Sexual Quality of Life Male Questionnaire. AB - Sexual dysfunction has been demonstrated to be related to a poor quality of life. These dysfunctions are especially prevalent among men. This cross-sectional study aimed to investigate the psychometric properties of the Persian translation of the Sexual Quality of Life-Male (SQOL-M), translated and adapted to measure sexual quality of life among Iranian men. Forward-backward procedures were applied in translating the original SQOL-M into Persian, and then the psychometric properties of the Persian translation of the SQOL-M were studied. A total of 181 participants (23-60 years old) were included in the study. Validity was assessed by construct validity using confirmatory factor analysis, convergent validity, and content validity. The international index of erectile function (IIEF) and the work ability index were used to study the convergent validity. Reliability was evaluated through internal consistency and test-retest reliability analyses. The results from confirmatory factor analysis confirmed a one-factor solution for the Persian version of the SQOL-M. Content validity of the translated measure was endorsed by 10 specialists. Pearson correlations indicated that work ability index score, dimensions of the IIEF, and the IIEF total score were positively correlated with the Persian version of the SQOL-M ( p < .001). Reliability evaluation indicated a high internal consistency and test retest reliability. The Cronbach's alpha coefficient and intraclass correlation coefficients were .96 and .95, respectively. Results indicated that the Persian version of the SQOL-M has good to excellent psychometric properties and can be used to assess the sexual quality of life among Iranian men. PMID- 26856760 TI - The remarkable activity and stability of a highly dispersive beta-brass Cu-Zn catalyst for the production of ethylene glycol. AB - Incorporation of Zn atoms into a nanosize Cu lattice is known to alter the electronic properties of Cu, improving catalytic performance in a number of industrially important reactions. However the structural influence of Zn on the Cu phase is not well studied. Here, we show that Cu nano-clusters modified with increasing concentration of Zn, derived from ZnO support doped with Ga(3+), can dramatically enhance their stability against metal sintering. As a result, the hydrogenation of dimethyl oxalate (DMO) to ethylene glycol, an important reaction well known for deactivation from copper nanoparticle sintering, can show greatly enhanced activity and stability with the CuZn alloy catalysts due to no noticeable sintering. HRTEM, nano-diffraction and EXAFS characterization reveal the presence of a small beta-brass CuZn alloy phase (body-centred cubic, bcc) which appears to greatly stabilise Cu atoms from aggregation in accelerated deactivation tests. DFT calculations also indicate that the small bcc CuZn phase is more stable against Cu adatom migration than the fcc CuZn phase with the ability to maintain a higher Cu dispersion on its surface. PMID- 26856762 TI - Trust pays cardiologist L1.22m for unfair dismissal. PMID- 26856761 TI - Adherence to the Dietary Approaches to Stop Hypertension-style diet in relation to glioma: a case-control study. AB - Data on the association of adherence to the Dietary Approaches to Stop Hypertension (DASH)-style and glioma are scarce. We aimed to examine the association between adherence to the DASH-style diet and glioma in Iranian adults. In this study, 128 pathologically confirmed cases of glioma were recruited from hospitals and 256 age- and sex-matched controls were enrolled from other wards of the hospital. Dietary intakes were assessed using a 126-item validated FFQ. Adherence to the DASH-style diet was followed considering the healthy and non-healthy foods emphasised in the DASH dietary pattern. After controlling for potential confounders, individuals with the greatest adherence to the DASH diet were 72 % less likely to have glioma compared with those with the lowest adherence (OR 0.28; 95 % CI 0.13, 0.57). Individuals with the highest consumption of fruits had lower odds for having glioma compared with those with the lowest intake (OR 0.31; 95 % CI 0.14, 0.68). A protective association was also observed between consumption of legumes and nuts and risk of glioma (OR 0.23; 95 % CI 0.10, 0.53). We found a significant positive association between red and processed meat (OR 2.60; 95 % CI 1.16, 5.81) and salt intakes (OR 2.87; 95 % CI 1.30, 6.34) and risk of glioma, after taking all potential confounders into account. Adherence to the DASH-style dietary pattern was inversely associated with glioma. In addition, some components of the DASH diet, including red meats and salt intakes, were positively associated with glioma. Consumption of nuts and legumes as well as fruits was inversely associated with glioma. Prospective cohort studies are required to confirm our findings. PMID- 26856763 TI - Influence of social mixing and group size on skin lesions and mounting in organic entire male pigs. AB - Alternatives to surgical castration are needed, due to stress and pain caused by castration of male pigs. One alternative is production of entire male pigs. However, changed behaviour of entire males compared with castrated males might adversely affect the welfare of entire males and changes in management procedures and production system might be needed. Elements from the organic pig production system might be beneficial in this aspect. The aim of this article is to investigate the effect of grouping strategy including social mixing and group size on levels of mounting behaviour and skin lesions, hypothesising that procedures that disrupt the social stability (e.g. regrouping) will have a larger negative effect in small groups compared with large groups. Approximately 1600 organic entire male pigs of the breed (Landrace*Yorkshire)*Duroc were reared in parallel in five organic herds, distributed across four batches in a 2*2 factorial design in order to test the influence of social mixing (presence or absence of social mixing at relocation) and group size (15 and 30 animals). Animals were able to socialise with piglets from other litters during the lactation period, and were all mixed across litters at weaning. A second mixing occurred at insertion to fattening pens for pigs being regrouped. Counting of skin lesions (1348 or 1124 pigs) and registration of mounting behaviour (1434 or 1258 pigs) were done on two occasions during the experimental period. No interactive effects were found between social mixing and group size on either skin lesions or mounting frequency. Herd differences were found for both mounting frequency and number of skin lesions. No association between skin lesions and mounting were revealed. Social mixing and group size were shown as interacting effects with herds on mounting frequency (P<0.0001), but with no consistent pattern across all herds. In addition, no effect of social mixing was found on mean number of skin lesions, but more lesions were observed in large groups (P<0.036). This could indicate that keeping entire male pigs in groups of 30 animals as compared with smaller groups of 15 may marginally decrease the welfare of these animals. PMID- 26856764 TI - A promising structure for fabricating high strength and high electrical conductivity copper alloys. AB - To address the trade-off between strength and electrical conductivity, we propose a strategy: introducing precipitated particles into a structure composed of deformation twins. A Cu-0.3%Zr alloy was designed to verify our strategy. Zirconium was dissolved into a copper matrix by solution treatment prior to cryorolling and precipitated in the form of Cu5Zr from copper matrix via a subsequent aging treatment. The microstructure evolutions of the processed samples were investigated by transmission electron microscopy and X-ray diffraction analysis, and the mechanical and physical behaviours were evaluated through tensile and electrical conductivity tests. The results demonstrated that superior tensile strength (602.04 MPa) and electrical conductivity (81.4% IACS) was achieved. This strategy provides a new route for balancing the strength and electrical conductivity of copper alloys, which can be developed for large-scale industrial application. PMID- 26856765 TI - Determination of Sodium Fluoroacetate in Dairy Powders by Liquid Chromatography Tandem Mass Spectrometry: Single-Laboratory Validation, First Action 2015.02. AB - A single-laboratory validation (SLV) study was conducted for the determination of sodium fluoroacetate in dairy powders by LC-tandem MS (LC-MS/MS). Linearity of response was confirmed by analysis of samples fortified over the concentration range 0.10-100 MUg/kg. The LOD was estimated to be 0.028 MUg/kg (0.028 ppb) from the SD of the measured concentrations of infant formula samples fortified at 0.10 MUg/kg. The corresponding LOQ calculates at 0.085 MUg/kg (0.085 ppb), which ensures excellent reliability of quantification at the limit of reporting of 1.0 MUg/kg (1 ppb). Repeatability and intermediate precision were estimated from the SD of the recovery of samples fortified at 0.075, 0.10, 0.20, 0.50, 1.0, and 10.0 MUg/kg. The previously mentioned method performance values were established using a representative stage 2 (6-12 months) bovine infant formula, and the robustness of the method was tested by the analysis of 107 unique dairy powders and formulations fortified at 1.0 MUg/kg. The data collected in this study satisfy the requirements of SLV studies established by the AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN), and the method was awarded First Action Official Method(SM) status by the AOAC Expert Review Panel on SPIFAN Nutrient Methods (Contaminants) on March 17, 2015. PMID- 26856766 TI - Capillary electrophoresis combined in-line with solid-phase extraction using magnetic particles as new adsorbents for the determination of drugs of abuse in human urine. AB - A simple approach is presented based on the in-line coupling between magnetic particles-based SPE and CE. Silica-coated iron oxide particles functionalized with C18 were successfully synthesized and used as a reverse-phase sorbent for in line SPE-CE. Magnets were used to locally immobilize these sorbents inside the capillary. Four drugs of abuse were preconcentrated and determined in urine samples using the developed method with a simple pretreatment procedure based on LLE. Several parameters affecting the preconcentration were evaluated. The obtained results show that this strategy enhanced detection sensitivity in the range of 125-700-fold compared with CE without preconcentration. The developed method provides LODs (S/N = 3) for standard samples in the range of 0.5-20 ng/mL with satisfactory analytical precision, in both intraday and day-to-day experiments (RSDs <20%). The LODs (S/N = 3) reached for urine samples were in the range of 20-50 ng/mL. Relative recoveries greater than 75.9% were obtained. The established method has been applied to the analysis of drugs of abuse in urine samples from drug abusers. PMID- 26856768 TI - The role of MMP genes in recurrent depressive disorders and cognitive functions. AB - OBJECTIVE: Among the 28 metalloproteinases described so far, 23 can be found in the human organism, but only few are expressed in the human brain. The main objective of this study was to analyse the relationship between MMP-2, MMP-9 and TIMP-2 gene expression and cognitive performance. METHODS: The study comprised 234 subjects: patients suffering from recurrent depressive disorder (rDD, n=139) and healthy subjects (HS, n=95). The cognitive function assessment was carried out with the help of the following tests: Trail Making Test, The Stroop Test, Verbal Fluency Test and Auditory Verbal Learning Test. Gene expression on the mRNA and protein level was evaluated for MMP-2, MMP-9 and TIMP-2 in both groups using RNA extraction, reverse transcription and enzyme-linked immunosorbent assay. RESULTS: Both mRNA and protein expression levels of all the genes were significantly lower in rDD subjects as compared with HS. Having analysed the entire experimental group (N=234), significant interrelations were found between the expression of the analysed genes and the results of the tests used to measure cognitive functions. Increased expression on both the mRNA and the protein level was associated in each case with better performance of all the tests conducted. After carrying out a separate analysis on the people from the rDD group and the HS group, similar dependencies were still observed. CONCLUSIONS: The results of our study show decreased expression of MMP-2, MMP-9 and TIMP-2 genes on both mRNA and protein levels in depression. Elevated expression of MMP-2, MMP-9, TIMP-2 positively affects cognitive efficiency: working memory, executive functions, attention functions, direct and delayed auditory-verbal memory, the effectiveness of learning processes and verbal fluency. The study highlights the important role of peripheral matrix metalloproteinases genes in depression and cognitive functions. PMID- 26856767 TI - Effects of Ureaplasma urealyticum Infection on Sperm Quality and Concentrations of Nitric Oxide and Cytokine in the Semen of Infertile Males. AB - PROBLEM: The relationship between genital infection and two sperm parameters, namely, concentrations of nitric oxide (NO) and cytokines [e.g., interleukin (IL) 17 and IL-18], in the semen of infertile males remains undetermined. METHOD OF STUDY: Semen samples from 81 infertile (with or without Ureaplasma urealyticum infection) and normal males were subjected to semen analysis. RESULTS: Nitric oxide concentration in the semen of infertile males with genital infection was higher than those of infertile males without genital infection and of normal males (P < 0.05). Sperm density, pH, percentage of forward, movement of sperm, sperm activation rate, sperm survival rate, and normal rate of the sperm morphology of infertile males with U. urealyticum infection were significantly lower than those of infertile males without genital infection and of normal males (P < 0.05). NO concentrations were also positively correlated with IL-17 and IL 18 concentrations in the semen of infertile males. CONCLUSION: Increased NO concentration and abnormal IL-17 and IL-18 expression were induced by genital infection and induced damage to male reproductive capacity, thereby causing male infertility. PMID- 26856769 TI - Justification for a 2D versus 3D fingertip finite element model during static contact simulations. AB - The biomechanical response of a human hand during contact with various products has not been investigated in details yet. It has been shown that excessive contact pressure on the soft tissue can result in discomfort, pain and also cumulative traumatic disorders. This manuscript explores the benefits and limitations of a simplified two-dimensional vs. an anatomically correct three dimensional finite element model of a human fingertip. Most authors still use 2D FE fingertip models due to their simplicity and reduced computational costs. However we show that an anatomically correct 3D FE fingertip model can provide additional insight into the biomechanical behaviour. The use of 2D fingertip FE models is justified when observing peak contact pressure values as well as displacement during the contact for the given studied cross-section. On the other hand, an anatomically correct 3D FE fingertip model provides a contact pressure distribution, which reflects the fingertip's anatomy. PMID- 26856770 TI - First ALPPS procedure using a total robotic approach. AB - BACKGROUND: ALPPS procedure is gaining interest. Indications and technical aspects of this technique are still under debate [1]. Only 4 totally laparoscopic ALPPS procedures have been described in the literature and none by robotic approach [2-4]. This video demonstrates the technical aspects of totally robotic ALPPS. METHODS: A 58 year old man with sigmoid adenocarcinoma with multiple right liver metastases extended to segment IV and I underwent Xelox and 5 Fluoro-uracil neoadjuvancy. Preoperative CT volumetric scan showed a FLR/TLV (Future Liver Remnant/Total Liver Volume) of 28%. ALPPS totally robotic procedure was planned using the DaVinci Si. RESULTS: Tumor resection from the FLR (including segment I) is followed by parenchymal transection between the FLR and the diseased part of the liver with concomitant right portal vein ligation. Small branches to segment IV from left portal vein have been resected along the round ligament, at this step. The right biliary tract was resected as it was partially debilitated after its dissection as partially encircled by a metastasis at segment IV. Second stage was performed totally robotic on 13th postoperative days with a FLR/TLV of 40%. No strong adherences are found, making this stage much easer than open approach. During this step, right hepatic artery and right supra hepatic vein are resected. Finally, the specimen was retrieved inside a plastic bag through a Pfannenstiel incision. Postoperative pathology showed margins free from disease. CONCLUSIONS: ALPPS procedure performed by robotic approach could be a safe and feasible technique in experienced centers with advanced robotic skills. PMID- 26856772 TI - Becoming a Team Player. PMID- 26856771 TI - Cytologic atypia in the contralateral unaffected breast is related to parity and estrogen-related genes. AB - PURPOSE: The contralateral unaffected breast (CUB) of women with unilateral breast cancer provides a model for the study of breast tissue-based risk factors. Using random fine needle aspiration (rFNA), we have investigated hormonal and gene expression patterns related to atypia in the CUBs of newly diagnosed breast cancer patients. METHODS: 83 women underwent rFNA of the CUB. Cytologic analysis was performed using the Masood Score (MS), atypia was defined as MS > 14. RNA was extracted using 80% of the sample. The expression of 20 hormone related genes was quantified using Taqman Low Density Arrays. Statistical analysis was performed using 2-tailed t tests and linear regression. RESULTS: Cytological atypia was more frequent in multiparous women (P = 0.0392), and was not associated with any tumor-related features in the affected breast. Masood Score was higher with shorter interval since last pregnancy (R = 0.204, P = 0.0417), higher number of births (R = 0.369, P = 0.0006), and estrogen receptor (ER) negativity of the index cancer (R = -0.203, P = 0.065). Individual cytologic features were associated with aspects of parity. Specifically, anisonucleosis was correlated with shorter interval since last pregnancy (R = 0.318, P = 0.0201), higher number of births (R = 0.382, P = 0.0004), and ER status (R = -0.314, P = 0.0038). Eight estrogen-regulated genes were increased in atypical samples (P < 0.005), including TFF1, AGT, PDZK1, PGR, GREB1, PRLR, CAMK2B, and CCND1. CONCLUSIONS: Cytologic atypia, and particularly anisonucleosis, is associated with recent and multiple births and ER negative status of the index tumor. Atypical samples showed increased expression of estrogen-related genes, consistent with the role of estrogen exposure in breast cancer development. PMID- 26856774 TI - Facile Preparation of Highly Conductive Metal Oxides by Self-Combustion for Solution-Processed Thermoelectric Generators. AB - Highly conductive indium zinc oxide (IZO) thin films were successfully fabricated via a self-combustion reaction for application in solution-processed thermoelectric devices. Self-combustion efficiently facilitates the conversion of soluble precursors into metal oxides by lowering the required annealing temperature of oxide films, which leads to considerable enhancement of the electrical conductivity of IZO thin films. Such enhanced electrical conductivity induced by exothermic heat from a combustion reaction consequently yields high performance IZO thermoelectric films. In addition, the effect of the composition ratio of In to Zn precursors on the electrical and thermoelectric properties of the IZO thin films was investigated. IZO thin films with a composition ratio of In:Zn = 6:2 at the low annealing temperature of 350 degrees C showed an enhanced electrical conductivity, Seebeck coefficient, and power factor of 327 S cm(-1), 50.6 MUV K(-1), and 83.8 MUW m(-1) K(-2), respectively. Moreover, the IZO thin film prepared at an even lower temperature of 300 degrees C retained a large power factor of 78.7 MUW m(-1) K(-2) with an electrical conductivity of 168 S cm( 1). Using the combustive IZO precursor, a thermoelectric generator consisting of 15 legs was fabricated by a printing process. The thermoelectric array generated a thermoelectric voltage of 4.95 mV at a low temperature difference (5 degrees C). We suggest that the highly conductive IZO thin films by self-combustion may be utilized for fabricating n-type flexible printed thermoelectric devices. PMID- 26856773 TI - NK cell maturation to CD56(dim) subset associated with high levels of NCRs overrides the inhibitory effect of NKG2A and recovers impaired NK cell cytolytic potential after allogeneic hematopoietic stem cell transplantation. AB - NK cell cytotoxicity against residual leukemic cells is crucial for immune system reconstitution after hematopoietic stem cell transplantation (HSCT). Since immune recovery after transplant still remains a major concern, we studied the counterbalance of NK cell receptors after HSCT and its importance in NK cell functional recovery. We investigated NK cell reconstitution in 27 acute leukemia patients at different time points following HLA-matched allogeneic HSCT compared to those of donors. NK cells were evaluated for their cytotoxicity in a standard (51)Cr-release assay against target cells and also analyzed for their receptors expression using flow cytometry. Early after transplant, we found higher percentage of CD56(bright) NK cells, increased levels of NKG2A and NCRs as well as decreased levels of KIRs expression on NK cells associated with an impaired cytotoxicity of these cells. All the abnormalities were normalized by one year after HSCT when CD56(bright) NK cells gradually differentiated into CD56(dim) subset. Collectively, we confirmed a gradual increase of CD56(dim) NK cells expressing NCRs with the significant decrease in NKG2A expression on NK cells. This finding was also associated with the recovery of NK cell cytotoxicity that suggests an important role for the kinetics of NK cell receptors during cell maturation in HSCT outcome. PMID- 26856775 TI - Tropheryma whipplei infection and Whipple's disease. AB - Recent advances in medical microbiology, epidemiology, cellular biology, and the availability of an expanded set of diagnostic methods such as histopathology, immunohistochemistry, PCR, and bacterial culture have improved our understanding of the clinical range and natural course of Tropheryma whipplei infection and Whipple's disease. Interdisciplinary and transnational research activities have contributed to the clarification of the pathogenesis of the disorder and have enabled controlled trials of different treatment strategies. We summarise the current knowledge and new findings relating to T whipplei infection and Whipple's disease. PMID- 26856776 TI - Detection of a novel Lyme borreliosis pathogen. PMID- 26856778 TI - Identifying components of self-management interventions that improve health related quality of life in chronically ill patients: Systematic review and meta regression analysis. AB - OBJECTIVE: To quantify diversity in components of self-management interventions and explore which components are associated with improvement in health-related quality of life (HRQoL) in patients with chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD), or type 2 diabetes mellitus (T2DM). METHODS: Systematic literature search was conducted from January 1985 through June 2013. Included studies were randomised trials in patients with CHF, COPD, or T2DM, comparing self-management interventions with usual care, and reporting data on disease-specific HRQoL. Data were analysed with weighted random effects linear regression models. RESULTS: 47 trials were included, representing 10,596 patients. Self-management interventions showed great diversity in mode, content, intensity, and duration. Although self-management interventions overall improved HRQoL at 6 and 12 months, meta-regression showed counterintuitive negative effects of standardised training of interventionists (SMD=-0.16, 95% CI: -0.31 to -0.01) and peer interaction (SMD=-0.23, 95% CI: -0.39 to 0.06) on HRQoL at 6 months. CONCLUSION: Self-management interventions improve HRQoL at 6 and 12 months, but interventions evaluated are highly heterogeneous. No components were identified that favourably affected HRQoL. Standardised training and peer interaction negatively influenced HRQoL, but the underlying mechanism remains unclear. PRACTICE IMPLICATIONS: Future research should address process evaluations and study response to self-management on the level of individual patients. PMID- 26856777 TI - Identification of a novel pathogenic Borrelia species causing Lyme borreliosis with unusually high spirochaetaemia: a descriptive study. AB - BACKGROUND: Lyme borreliosis is the most common tick-borne disease in the northern hemisphere. It is a multisystem disease caused by Borrelia burgdorferi sensu lato genospecies and characterised by tissue localisation and low spirochaetaemia. In this study we aimed to describe a novel Borrelia species causing Lyme borreliosis in the USA. METHODS: At the Mayo clinic, from 2003 to 2014, we tested routine clinical diagnostic specimens from patients in the USA with PCR targeting the oppA1 gene of B burgdorferi sensu lato. We identified positive specimens with an atypical PCR result (melting temperature outside of the expected range) by sequencing, microscopy, or culture. We collected Ixodes scapularis ticks from regions of suspected patient tick exposure and tested them by oppA1 PCR. FINDINGS: 100 545 specimens were submitted by physicians for routine PCR from Jan 1, 2003 to Sept 30, 2014. From these samples, six clinical specimens (five blood, one synovial fluid) yielded an atypical oppA1 PCR product, but no atypical results were detected before 2012. Five of the six patients with atypical PCR results had presented with fever, four had diffuse or focal rash, three had symptoms suggestive of neurological inclusion, and two were admitted to hospital. The sixth patient presented with knee pain and swelling. Motile spirochaetes were seen in blood samples from one patient and cultured from blood samples from two patients. Among the five blood specimens, the median oppA1 copy number was 180 times higher than that in 13 specimens that tested positive for B burgdorferi sensu stricto during the same time period. Multigene sequencing identified the spirochaete as a novel B burgdorferi sensu lato genospecies. This same genospecies was detected in ticks collected at a probable patient exposure site. INTERPRETATION: We describe a new pathogenic Borrelia burgdorferi sensu lato genospecies (candidatus Borrelia mayonii) in the upper midwestern USA, which causes Lyme borreliosis with unusually high spirochaetaemia. Clinicians should be aware of this new B burgdorferi sensu lato genospecies, its distinct clinical features, and the usefulness of oppA1 PCR for diagnosis. FUNDING: US Centers for Disease Control and Prevention Epidemiology and Laboratory Capacity for Infectious Diseases (ELC) Cooperative Agreement and Mayo Clinic Small Grant programme. PMID- 26856779 TI - Severe Acute Cardiopulmonary Failure Related to Gadobutrol Magnetic Resonance Imaging Contrast Reaction: Successful Resuscitation With Extracorporeal Membrane Oxygenation. AB - Nonanaphylactic noncardiogenic pulmonary edema leading to cardiorespiratory arrest related to the magnetic resonance imaging contrast agent gadobutrol has rarely been reported in the literature. Rarer is the association of hypokalemia with acidosis. We report 2 patients who had severe pulmonary edema associated with the use of gadobutrol contrast in the absence of other inciting agents or events. These cases were unique not only for their rare and severe presentations but also because they exemplified the increasing role of extracorporeal membrane oxygenation in resuscitation. Emergency extracorporeal membrane oxygenation resuscitation can be rapidly initiated and successful in the setting of a well organized workflow, and it is a viable alternative and helps improve patient outcome in cases refractory to conventional resuscitative measures. PMID- 26856780 TI - Incidence and Predictors of Infective Endocarditis in Mitral Valve Prolapse: A Population-Based Study. AB - OBJECTIVE: To determine the incidence and predictors of infective endocarditis (IE) in a population-based cohort of patients with mitral valve prolapse (MVP). PATIENTS AND METHODS: We identified all adult Olmsted County residents with MVP diagnosed by echocardiography from January 1989 to December 1998 and cross matched them with the Rochester Epidemiology Project-identified Olmsted County cases of IE from January 1, 1986, through December 31, 2006. We retrospectively analyzed and de novo confirmed each IE case using the modified Duke criteria. RESULTS: There were 896 Olmsted County residents with echocardiographically diagnosed MVP (mean age, 53+/-21 years; 565 women [63%]). The mean follow-up period was 11+/-5 years. The 15-year cohort risk of IE after MVP diagnosis was 1.1%+/-0.4% (incidence, 86.6 cases per 100,000 person-years; 95% CI, 43.3-173.2 cases per 100,000 person-years); thus, the age- and sex-adjusted relative risk of IE in patients with MVP was 8.1 (95% CI, 3.6-18.0) in comparison to the general population of Olmsted County (P<.001). There were no IE cases in patients without previously diagnosed mitral regurgitation (MR). Conversely, IE incidence was higher in patients with MVP with moderate, moderate-severe, or severe MR (289.5 cases per 100,000 person-years; 95% CI, 108.7-771.2 cases per 100,000 person years; P=.02 compared with trivial, mild, or mild-moderate MR) and in patients with a flail mitral leaflet (715.5 cases per 100,000 person-years; 95% CI, 178.9 2861.0 cases per 100,000 person-years; P=.02 compared with no flail mitral leaflet). CONCLUSION: The population-based incidence of IE in adults with MVP is higher than those previously reported in case-control, tertiary care center studies. Patients with MVP and moderate, moderate-severe, or severe MR or a flail mitral leaflet are at a notable risk of developing IE in comparison with those without MR. PMID- 26856781 TI - Peripubertal treatment with cannabidiol prevents the emergence of psychosis in an animal model of schizophrenia. PMID- 26856782 TI - Trigeminal Lymphoma and Its Many Faces. PMID- 26856783 TI - Influence of Parkinsonism on Hitler's Decision-Making. PMID- 26856784 TI - In Reply to the Letter to the Editor, "Influence of Parkinsonism on Hitler's Decision-Making". PMID- 26856785 TI - Letter to the Editor Regarding "Adjacent Level Ligamentous Injury Associated with Traumatic Cervical Spine Fractures: Indications for Imaging and Implications for Treatment". PMID- 26856786 TI - In Reply to the Letter to the Editor Regarding "Adjacent Level Ligamentous Injury Associated with Traumatic Cervical Spine Fractures: Indications for Imaging and Implications for Treatment". PMID- 26856787 TI - Women in Neurosurgery: A New Paradigm of Thought Will Emerge. PMID- 26856789 TI - Recent Advances in Organic Photovoltaics: Device Structure and Optical Engineering Optimization on the Nanoscale. AB - Organic photovoltaic (OPV) devices, which can directly convert absorbed sunlight to electricity, are stacked thin films of tens to hundreds of nanometers. They have emerged as a promising candidate for affordable, clean, and renewable energy. In the past few years, a rapid increase has been seen in the power conversion efficiency of OPV devices toward 10% and above, through comprehensive optimizations via novel photoactive donor and acceptor materials, control of thin film morphology on the nanoscale, device structure developments, and interfacial and optical engineering. The intrinsic problems of short exciton diffusion length and low carrier mobility in organic semiconductors creates a challenge for OPV designs for achieving optically thick and electrically thin device structures to achieve sufficient light absorption and efficient electron/hole extraction. Recent advances in the field of OPV devices are reviewed, with a focus on the progress in device architecture and optical engineering approaches that lead to improved electrical and optical characteristics in OPV devices. Successful strategies are highlighted for light wave distribution, modulation, and absorption promotion inside the active layer of OPV devices by incorporating periodic nanopatterns/nanostructures or incorporating metallic nanomaterials and nanostructures. PMID- 26856788 TI - A Broadband Polyvinylidene Difluoride-Based Hydrophone with Integrated Readout Circuit for Intravascular Photoacoustic Imaging. AB - Intravascular photoacoustic (IVPA) imaging can visualize the coronary atherosclerotic plaque composition on the basis of the optical absorption contrast. Most of the photoacoustic (PA) energy of human coronary plaque lipids was found to lie in the frequency band between 2 and 15 MHz requiring a very broadband transducer, especially if a combination with intravascular ultrasound is desired. We have developed a broadband polyvinylidene difluoride (PVDF) transducer (0.6 * 0.6 mm, 52 MUm thick) with integrated electronics to match the low capacitance of such a small polyvinylidene difluoride element (<5 pF/mm(2)) with the high capacitive load of the long cable (~100 pF/m). The new readout circuit provides an output voltage with a sensitivity of about 3.8 MUV/Pa at 2.25 MHz. Its response is flat within 10 dB in the range 2 to 15 MHz. The root mean square (rms) output noise level is 259 MUV over the entire bandwidth (1-20 MHz), resulting in a minimum detectable pressure of 30 Pa at 2.25 MHz. PMID- 26856790 TI - Implantation of the Micra Transcatheter Pacing System: Initial Experience in a Single Spanish Center. PMID- 26856791 TI - Update: Cardiac Imaging (II). Transcatheter Aortic Valve Replacement: Advantages and Limitations of Different Cardiac Imaging Techniques. AB - Transcatheter aortic valve replacement is an established therapy for patients with symptomatic severe aortic stenosis and contraindications or high risk for surgery. Advances in prostheses and delivery system designs and continuous advances in multimodality imaging, particularly the 3-dimensional techniques, have led to improved outcomes with significant reductions in the incidence of frequent complications such as paravalvular aortic regurgitation. In addition, data on prosthesis durability are accumulating. Multimodality imaging plays a central role in the selection of patients who are candidates for transcatheter aortic valve replacement, procedure planning and guidance, and follow-up of prosthesis function. The strengths and limitations of each imaging technique for transcatheter aortic valve replacement will be discussed in this update article. PMID- 26856792 TI - Maximum Low-density Lipoprotein Cholesterol Lowering Capacity Achievable With Drug Combinations. When 50 Plus 20 Equals 60. PMID- 26856793 TI - Plan of Action for Inherited Cardiovascular Diseases: Synthesis of Recommendations and Action Algorithms. AB - The term inherited cardiovascular disease encompasses a group of cardiovascular diseases (cardiomyopathies, channelopathies, certain aortic diseases, and other syndromes) with a number of common characteristics: they have a genetic basis, a familial presentation, a heterogeneous clinical course, and, finally, can all be associated with sudden cardiac death. The present document summarizes some important concepts related to recent advances in sequencing techniques and understanding of the genetic bases of these diseases. We propose diagnostic algorithms and clinical practice recommendations and discuss controversial aspects of current clinical interest. We highlight the role of multidisciplinary referral units in the diagnosis and treatment of these conditions. PMID- 26856796 TI - Prostate cancer diagnosis by optical coherence tomography: First results from a needle based optical platform for tissue sampling. AB - The diagnostic accuracy of Optical Coherence Tomography (OCT) based optical attenuation coefficient analysis is assessed for the detection of prostate cancer. Needle-based OCT-measurements were performed on the prostate specimens. Attenuation coefficients were determined by an earlier described in-house developed software package. The mean attenuation coefficients (benign OCT data; malignant OCT data; p-value Mann-Whitney U test) were: (3.56 mm(-1) ; 3.85 mm(-1) ; p < 0.0001) for all patients combined. The area under the ROC curve was 0.64. In order to circumvent the effect of histopathology mismatching, we performed a sub-analysis on only OCT data in which tumor was visible in two subsequent histopathological prostate slices. This analysis could be performed in 3 patients. The mean attenuation coefficients (benign OCT data; malignant OCT data; p-value Mann-Whitney U test) were: (3.23 mm(-1) ; 4.11 mm(-1) ; p < 0.0001) for all patients grouped together. The area under the ROC curve was 0.89. Functional OCT of the prostate has shown to differentiate between cancer and healthy prostate tissue. The optical attenuation coefficient in malignant tissue was significantly higher in malignant tissue compared to benign prostate tissue. Further studies are required to validate these initial results in a larger group of patients with a more tailored histopathology matching protocol. PMID- 26856795 TI - Blood Pressure Control Provides Less Cardiovascular Protection in Adults With Than Without Apparent Treatment-Resistant Hypertension. AB - Hypertension control may offer less protection from incident cardiovascular disease (CVDi ) in adults with than without apparent treatment-resistant hypertension (aTRH), ie, blood pressure uncontrolled while taking three or more antihypertensive medications or controlled to <140/<90 mm Hg while taking four or more antihypertensive medications. Electronic health data were matched to health claims for 2006-2012. Patients with CVDi in 2006-2007 or with untreated hypertension were excluded, leaving 118,356 treated hypertensives, including 40,690 with aTRH, and 460,599 observation years. Blood pressure and medication number were determined by all clinic visit means from 2008 to CVDi or end of study. Primary outcome was first CVDi (stroke, coronary heart disease, heart failure) from hospital and emergency department claims. Controlling for age, race, sex, diabetes, chronic kidney disease, and statin use, hypertension control afforded less CVDi protection in patients with aTRH (hazard ratio, 0.87; 95% confidence interval, 0.82-0.93) than without aTRH (hazard ratio, 0.69; 95% confidence interval, 0.65-0.74; P<.001). Strategies beyond hypertension control may prevent more CVDi in patients with aTRH. PMID- 26856794 TI - Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer. AB - Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type and is characterized by a dismal prognosis due to late diagnosis, local tumor invasion, frequent distant metastases and poor sensitivity to current therapy. In this context, circulating tumor cells and circulating tumor DNA constitute easily accessible blood-borne tumor biomarkers that may prove their clinical interest for screening, early diagnosis and metastatic risk assessment of PDAC. Moreover these markers represent a tool to assess PDAC mutational landscape. In this review, together with key biological findings, we summarize the clinical results obtained using "liquid biopsies" at the different stages of the disease, for early and metastatic diagnosis as well as monitoring during therapy. PMID- 26856797 TI - Cichlids of the Banc d'Arguin National Park, Mauritania: insight into the diversity of the genus Coptodon. AB - To determine the species diversity of cichlids in the Banc d'Arguin National Park (PNBA) and their phylogenetic relationships with other species in West Africa, a morphometric and meristic and molecular phylogenetic study was conducted. Both approaches not only confirm the presence of Sarotherodon melanotheron in PNBA but also demonstrate the presence of a second species from the genus Coptodon. While morphometric characteristics match the description of the Guinean tilapia Coptodon guineensis, phylogenetic reconstructions based on three mitochondrial and one nuclear DNA fragment demonstrate that C. guineensis is paraphyletic over its range. Because different lineages of C. guineensis are allopatric, the distribution of C. guineensis should be restricted to Ghana and Cote d'Ivoire. The many other lineages of this species should be considered as C. sp. aff. guineensis. PMID- 26856799 TI - Peer review: Least-worst approach or the very best we can do? PMID- 26856798 TI - Examining the Sociocultural Context of HIV-related Risk Behaviors Among Kathoey (Male-to-female Transgender Women) Sex Workers in Bangkok, Thailand. AB - Kathoey (male-to-female transgender) sex workers (KSW) in Thailand are at high risk for sexually transmitted infections; however, few qualitative studies have been conducted to understand the sociocultural context of engaging in HIV risk behaviors. A total of 24 participants were purposively sampled in Bangkok based on KSW work venues and substance use. Results revealed the importance of participants' understanding of the self in relation to establishing economic independence through sex work, which could then be used to re-establish support from family, who often have not accepted a son's gender transition. Participants linked being kathoey to a belief in fate but did not view engagement in sex work in the same way. Different sex work venues exposed KSW to different risky situations. HIV prevention programs for kathoey must address the importance of economic security and its relation to social support and gender transition within a cultural- and work-environment-specific framework. PMID- 26856800 TI - Organisational support for evidence-based practice: occupational therapists perceptions. AB - BACKGROUND: Barriers to the use of evidence-based practice extend beyond the individual clinician and often include organisational barriers. Adoption of systematic organisational support for evidence-based practice in health care is integral to its use. This study aimed to explore the perceptions of occupational therapy staff regarding the influence of organisational initiatives to support evidence-based practice on workplace culture and clinical practice. METHODS: This study used semi-structured interviews with 30 occupational therapists working in a major metropolitan hospital in Brisbane, Australia regarding their perceptions of organisational initiatives designed to support evidence-based practice. RESULTS: Four themes emerged from the data: (i) firmly embedding a culture valuing research and EBP, (ii) aligning professional identity with the Research and Evidence in Practice model, (iii) experiences of change: pride, confidence and pressure and (iv) making evidence-based changes to clinical practices. CONCLUSION: Organisational initiatives for evidence-based practice were perceived as influencing the culture of the workplace, therapists' sense of identity as clinicians, and as contributing to changes in clinical practice. It is therefore important to consider organisational factors when attempting to increase the use of evidence in practice. PMID- 26856801 TI - Understanding decision-making towards housework among women with upper limb repetitive strain injury. AB - BACKGROUND: Among women with upper limb repetitive strain injury (RSI), occupational therapy interventions include education to facilitate ergonomic practices in housework. From a client-centred perspective, an understanding of women's decision-making about housework is needed to design effective occupational therapy programmes. This study addresses a gap in research in this area by exploring women's views about changing housework habits. AIM: The aim was to construct a conceptual representation to explain decision-making in housework by drawing on experiences of a sample of Singapore Chinese women with upper limb RSI from one hand therapy clinic. METHODS: Based on a constructivist grounded theory methodology, data were collected through in-depth interviewing with 15 women. Interviews were audiotaped and transcribed. Data were analysed with line by line coding, focussed coding and axial coding with constant comparison throughout data collection. RESULTS: Decision-making in housework among these women involved three main themes: (i) emotional attachment to housework; (ii) cognitively informed decision; and (iii) emotionally influenced decision. Women with upper limb RSI had to make cognitive decisions for or against a change in housework to manage their condition. However, the women's cognitively informed decisions were shaped by their emotional attachment to housework. As such, they experienced strong emotional barriers to changing their housework practices even when they had cognitively accepted the necessity and possibility of making a change. CONCLUSIONS: Therapists need to be aware that counselling to address the emotional barriers experienced by women is important during ergonomic education. PMID- 26856803 TI - Workplace resilience interventions show some evidence of positive effects, particularly on mental health and wellbeing. PMID- 26856802 TI - Initial validation of the dimensions of home measure. AB - BACKGROUND: Research has established a need to consider further aspects of the home environment in home modification provision and evaluation. The Dimensions of Home Measure (DOHM) was developed as a self-report outcome measurement tool for home modification practice to meet this need. Its development was informed by a literature review and qualitative exploration which identified six dimensions of the home environment: the physical, social, personal, temporal, occupational and societal dimensions which contribute to one's experience of home. This paper reports the initial evaluation of the validity of the DOHM. METHOD: The DOHM was completed by 163 community dwelling older adults and people with disabilities. The Rasch measurement model was used to evaluate three aspects of construct validity: rating scale structure, unidimensionality and targeting. RESULTS: The five-point DOHM rating scale function was evaluated using Linacre's (2002) guidelines. The middle rating category did not function well, and this resulted in collapsing the rating scale from five to four points. The unidimensionality of the DOHM's subscales was supported by Rasch-based principal component analysis and item fit analysis. However, hierarchical results of item difficulties revealed significant gaps in each of the DOHM's subscales, indicating that more items will be needed to capture the full range of participant's experiences of home. CONCLUSION: The DOHM was developed to provide a relevant evaluation tool for home modification practice which comprehensively measures the home environment. This study identified preliminary validity of this tool, with revision and further psychometric validation required. PMID- 26856804 TI - Injury prevention in the meat industry: Limited evidence of effectiveness for ergonomic programs in reducing the severity of musculoskeletal injuries. PMID- 26856806 TI - Bayesian linear regression with skew-symmetric error distributions with applications to survival analysis. AB - We study Bayesian linear regression models with skew-symmetric scale mixtures of normal error distributions. These kinds of models can be used to capture departures from the usual assumption of normality of the errors in terms of heavy tails and asymmetry. We propose a general noninformative prior structure for these regression models and show that the corresponding posterior distribution is proper under mild conditions. We extend these propriety results to cases where the response variables are censored. The latter scenario is of interest in the context of accelerated failure time models, which are relevant in survival analysis. We present a simulation study that demonstrates good frequentist properties of the posterior credible intervals associated with the proposed priors. This study also sheds some light on the trade-off between increased model flexibility and the risk of over-fitting. We illustrate the performance of the proposed models with real data. Although we focus on models with univariate response variables, we also present some extensions to the multivariate case in the Supporting Information. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26856807 TI - Evaluating outcome of prophylaxis in haemophilia: objective and self-reported instruments should be combined. AB - INTRODUCTION: Routine outcome assessment of prophylaxis should use validated tools, while balancing comprehensiveness and burden. Collecting overlapping information should be avoided. AIM: To assess correlations between different outcome assessment tools in haemophilia. METHODS: From an international cross sectional study, data on objective outcome (Haemophilia Joint Health Score (HJHS 2.1, range 0-124), radiological Pettersson score) and self-reported joint bleeding, Haemophilia Activities List (HAL, range 100-0), health-related quality of life (SF-36, including five physical and five mental domain scores, range 100 0), and Utility (SF6D and EQ-5D, range 1.0-0) were extracted. Spearman's correlations were calculated: >=0.8 very strong, 0.60-0.79 strong, 0.40-0.59 moderate. RESULTS: Ninety patients with severe haemophilia, on prophylaxis since median age 3.4 years, were evaluated at median 25.5 years (range 16.0-37.6). Objective outcome was favourable (median HJHS 2.1 6 points, Pettersson score 9 points). Self-reported outcome showed a median of 7 joint bleeds in 5 years, median HAL sum 96 points, high scores for physical domains of SF-36 (median 80 95) and high Utility values (median SF6D 0.87; EQ-5D 0.84). Physical examination (HJHS 2.1) showed strong correlation with radiological scores, moderate correlation with physical domains of the SF-36 and Utility, but no correlation with self-reported bleeding or limitations in activities (HAL). Bleeding was not associated with any other outcome parameter. The HAL was only correlated with the SF36 'Physical functioning' domain. CONCLUSION: For the evaluation of patients on early prophylaxis, information on bleeding should be complemented by objective joint assessment as well as self-reported limitations in activities and quality of life. PMID- 26856809 TI - Acrodermatitis Dysmetabolica in a Child with Cystic Fibrosis. AB - Acrodermatitis dysmetabolica is an umbrella term encompassing the other metabolic causes of an erosive periorificial and acral dermatitis that mimics acrodermatitis enteropathica. Causes include acquired zinc, amino acid, biotin, and fatty acid deficiencies. We present the case of an exclusively breastfed, 2 month-old boy with known cystic fibrosis admitted with failure to thrive and erosive dermatitis. A diagnosis of acrodermatitis dysmetabolica was made when investigations revealed a normal zinc level but low amino acid levels. PMID- 26856808 TI - Applying a Part of the Daily Dose as Boli May Improve Intrathecal Opioid Therapy in Patients With Chronic Pain. AB - OBJECTIVES: The speed of intrathecal drug administration (slow continuous infusion vs. rapid bolus application) might influence the efficacy of therapy despite the equal daily dose in both administration patterns. We tested this hypothesis in a small prospective single-centre pilot study in a population of chronic pain patients with intrathecal opioid therapy. METHODS: Ten patients receiving intrathecal opioids for chronic pain assessed their pain four times daily on a numeric rating scale (NRS), more than the time course of six weeks divided into three blocks of two weeks each: Baseline evaluation (intrathecal pumps with previously established continuous infusion settings), followed by two blinded trial blocks of continuous (same pump parameters as during evaluation) and bolus (40% of daily dose split into four equal boli applied every six hours, with the remaining 60% as background continuous infusion) regimes. Patients were randomized in a crossover fashion. RESULTS: 6/10 patients reported significantly lower NRS-scores during bolus as compared to continuous trial blocks while only one patient showed the opposite effect. Overall, bolus trial blocks were associated with a small but significant reduction of NRS-scores (mean -0.56; p < 0.0001). Side-effects related to bolus infusions were not reported. CONCLUSIONS: Intermittent bolus administration may be helpful for increasing the efficacy of intrathecal opioid therapy of chronic pain. PMID- 26856810 TI - Pharmacology for sleep disturbance in PTSD. AB - Symptoms of sleep disturbance, particularly nightmares and insomnia, are a central feature of post-traumatic stress disorder (PTSD). Emerging evidence suggests that specific treatment of PTSD-related sleep disturbance improves other symptoms of the disorder, which in turn suggests that such disturbance may be fundamental to development and maintenance of the disorder. This mini-review focuses on pharmacological treatment of sleep disturbance in adult PTSD (specifically, studies testing the efficacy of antidepressants, adrenergic inhibiting agents, antipsychotics and benzodiazepine and non-benzodiazepine hypnotics). We conclude that only prazosin, an adrenergic inhibiting agent, has had its efficacy established by multiple randomised controlled trials. There is also high-level evidence supporting use of eszopiclone, as well as risperidone and olanzapine as adjunct therapy. Antidepressants such as sertraline, venlafaxine and mirtazapine, benzodiazepines such as alprazolam and clonazepam and non-benzodiazepine hypnotics such as zolpidem appear ineffective in treating PTSD-related sleep disturbance. Most studies that report reduced frequency of nightmares and insomnia also report decreases in overall symptom severity. Such findings suggest that (i) sleep disruption is central to PTSD; (ii) treating sleep disruption may be an effective way to address other symptoms of the disorder and (iii) PTSD symptoms tend to cluster together in predictable ways. PMID- 26856811 TI - Educational differences in the validity of self-reported physical activity. AB - BACKGROUND: The assessment of physical activity for surveillance or population based studies is usually done with self-report questionnaires. However, bias in self-reported physical activity may be greater in lower educated than in higher educated populations. The aim of the present study is to describe educational differences in the validity of self-reported physical activity. METHODS: We included 196 healthy adults (age 57 +/- 15.4, of whom 17% low, 24% medium and 59% high educated). Criterion validity of an adapted International Physical Activity Questionnaire was assessed against the ActiGraph GT3X+ accelerometer. RESULTS: While criterion validity of self-reported physical activity was low to moderate in the total sample (Spearman rho ranged from 0.16 to 0.27, depending on the variables used), the validity in lower educated respondents was poor (-0.07 to 0.05). CONCLUSIONS: The results confirm the hypothesis that self-report physical activity questionnaires are less valid in lower educated populations. PMID- 26856813 TI - Participation and health care provision of statutory skin cancer screening in Germany - a secondary data analysis. AB - BACKGROUND: In Germany, skin cancer screening was introduced nationwide in July 2008. From the age of 35 years, members of the statutory health insurance are eligible for screening every 2 years. OBJECTIVE: The aim of this study is to calculate the participation rates and the proportions of health care providers of statutory skin cancer screening in Germany on a population-based level. METHODS: Data were provided by a nationwide German statutory health insurance, approximately 6.1 million members, covering the years 2008/2009. Participation rates were calculated per yearly quarter and were adjusted for age, gender and federal state. RESULTS: Approximately 920,000 insurants were screened from the third quarter of 2008 until the last quarter of 2009. Mean participation rate of skin cancer screening was 30.8%. Women had higher participation rates (31.9%) than men (29.7%). After adjusting for gender and federal state, high rates for pensioners at the age of 65-74 were confirmed at 39.4% on average for all yearly quarters. One of the highest gender- and age-adjusted rates was observed in the state of Schleswig-Holstein, where a population based pilot project had been implemented before the start of the nationwide screening programme. In general, without taking into account Berlin, former East Germany had a much lower gender- and age-adjusted participation rate (23.9%) than West Germany (33.3%). At the first quarter after implementation of screening, 58.5% of the screenings were provided by dermatologists and 41.5% by general practitioners. CONCLUSION: Participation rates and health care providers of skin cancer screening can be calculated from secondary data and contribute to identify group- and region specific participation patterns in order to improve early detection of skin cancer. PMID- 26856812 TI - Astaxanthin ameliorates prenatal LPS-exposed behavioral deficits and oxidative stress in adult offspring. AB - BACKGROUND: Prenatal maternal lipopolysaccharide (LPS) exposure leads to behavioral deficits such as depression, anxiety, and schizophrenia in the adult lives. LPS-exposure resulted in the production of cytokines and oxidative damage. On the contrary, astaxanthin is a carotenoid compound, showed neuroprotective properties via its antioxidant capacity. This study examines the effect of astaxanthin on the prenatal maternal LPS-induced postnatal behavioral deficit in mice. RESULTS: We found that prenatal LPS-exposed mice showed extensive immobile phase in the tail suspension test, higher frequent head dipping in the hole-board test and greater hypolocomotion in the open field test. All these values were statistically significant (p < 0.05). In addition, a marked elevation of the level of lipid peroxidation, advanced protein oxidation product, nitric oxide, while a pronounced depletion of antioxidant enzymes (superoxide dismutase, catalase and glutathione) were observed in the adult offspring mice that were prenatally exposed to LPS. To the contrary, 6-weeks long treatment with astaxanthin significantly improved all behavioral deficits (p < 0.05) and diminished prenatal LPS-induced oxidative stress markers in the brain and liver. CONCLUSIONS: Taken together, these results suggest that prenatal maternal LPS exposure leads to behavioral deficits in the adults, while astaxanthin ameliorates the behavioral deficits presumably via its antioxidant property. PMID- 26856815 TI - Validation of an automated colony counting system for group A Streptococcus. AB - BACKGROUND: The practice of counting bacterial colony forming units on agar plates has long been used as a method to estimate the concentration of live bacteria in culture. However, due to the laborious and potentially error prone nature of this measurement technique, an alternative method is desirable. Recent technologic advancements have facilitated the development of automated colony counting systems, which reduce errors introduced during the manual counting process and recording of information. An additional benefit is the significant reduction in time taken to analyse colony counting data. Whilst automated counting procedures have been validated for a number of microorganisms, the process has not been successful for all bacteria due to the requirement for a relatively high contrast between bacterial colonies and growth medium. The purpose of this study was to validate an automated counting system for use with group A Streptococcus (GAS). RESULTS: METHODS: Twenty-one different GAS strains, representative of major emm-types, were selected for assessment. In order to introduce the required contrast for automated counting, 2,3,5-triphenyl-2H tetrazolium chloride (TTC) dye was added to Todd-Hewitt broth with yeast extract (THY) agar. Growth on THY agar with TTC was compared with growth on blood agar and THY agar to ensure the dye was not detrimental to bacterial growth. Automated colony counts using a ProtoCOL 3 instrument were compared with manual counting to confirm accuracy over the stages of the growth cycle (latent, mid-log and stationary phases) and in a number of different assays. The average percentage differences between plating and counting methods were analysed using the Bland Altman method. CONCLUSIONS: RESULTS: A percentage difference of +/-10 % was determined as the cut-off for a critical difference between plating and counting methods. All strains measured had an average difference of less than 10 % when plated on THY agar with TTC. This consistency was also observed over all phases of the growth cycle and when plated in blood following bactericidal assays. Agreement between these methods suggest the use of an automated colony counting technique for GAS will significantly reduce time spent counting bacteria to enable a more efficient and accurate measurement of bacteria concentration in culture. PMID- 26856814 TI - The dual S1PR1/S1PR5 drug BAF312 (Siponimod) attenuates demyelination in organotypic slice cultures. AB - BACKGROUND: BAF312 (Siponimod) is a dual agonist at the sphingosine-1 phosphate receptors, S1PR1 and S1PR5. This drug is currently undergoing clinical trials for the treatment of secondary progressive multiple sclerosis (MS). Here, we investigated the effects of BAF312 on isolated astrocyte and microglia cultures as well as in slice culture models of demyelination. METHODS: Mouse and human astrocytes were treated with S1PR modulators and changes in the levels of pERK, pAkt, and calcium signalling as well as S1PR1 internalization and cytokine levels was investigated using Western blotting, immunochemistry, ELISA and confocal microscopy. Organotypic slice cultures were prepared from the cerebellum of 10 day-old mice and treated with lysophosphatidylcholine (LPC), psychosine and/or S1PR modulators, and changes in myelination states were measured by fluorescence of myelin basic protein and neurofilament H. RESULTS: BAF312 treatment of human and mouse astrocytes activated pERK, pAKT and Ca(2+) signalling as well as inducing S1PR1 internalization. Notably, activation of S1PR1 increased pERK and pAKT in mouse astrocytes while both S1PR1 and S1PR3 equally increased pERK and pAKT in human astrocytes, suggesting that the coupling of S1PR1 and S1PR3 to pERK and pAKT differ in mouse and human astrocytes. We also observed that BAF312 moderately attenuated lipopolysaccharide (LPS)- or TNFalpha/IL17-induced levels of IL6 in both astrocyte and microglia cell cultures. In organotypic slice cultures, BAF312 reduced LPC-induced levels of IL6 and attenuated LPC-mediated demyelination. We have shown previously that the toxic lipid metabolite psychosine induces demyelination in organotypic slice cultures, without altering the levels of cytokines, such as IL6. Importantly, psychosine-induced demyelination was also attenuated by BAF312. CONCLUSIONS: Overall, this study suggests that BAF312 can modulate glial cell function and attenuate demyelination, highlighting this drug as a further potential therapy in demyelinating disorders, beyond MS. PMID- 26856816 TI - Patient decision aids for prevention and treatment of cancer diseases: are they really personalised tools? AB - This article provides an analysis of cancer decision aids (DAs), instruments developed to support oncologic patients facing tough screening or treatment decisions, with a particular attention to their level of personalisation. As discussed in our previous works, we argue that the personalisation of medicine should regard not only the genetic and clinical aspects of diseases but also the different cognitive, psychological and social factors involved in clinical choices. According to this vision, we analysed the existing randomised controlled studies on cancer DAs concluding that only few of them take into account individual variables such as cultural level, individual risk attitudes, personal beliefs, and emotional state that are crucial to determine people's reactions and health-related choices. For these reasons, although quality standards have been published for these interventions, we suggest the need for further research in order to make these instruments more efficient in transforming and improving the actual clinical practice, improving patient empowerment and participation in health-related decisions. PMID- 26856817 TI - Evidence for Bombus occidentalis (Hymenoptera: Apidae) Populations in the Olympic Peninsula, the Palouse Prairie, and Forests of Northern Idaho. AB - Since the mid-1990s, Bombus occidentalis (Green) has declined from being one of the most common to one of the rarest bumble bee species in the Pacific Northwest of the United States. Although its conservation status is unresolved, a petition to list this species as endangered or threatened was recently submitted to the U.S. Fish and Wildlife Service. To shed light on the conservation situation and inform the U.S. Fish and Wildlife Service decision, we report on the detection and abundance of B. occidentalis following bumble bee collection between 2012 and 2014 across the Pacific Northwest. Collection occurred from the San Juan Islands and Olympic peninsula east to northern Idaho and northeastern Oregon, excluding the arid region in central Washington. B. occidentalis was observed at 23 collection sites out of a total of 234. With the exception of three sites on the Olympic peninsula, all of these were in the southeastern portion of the collection range. PMID- 26856819 TI - Scleral tunnel intraocular lens explantation: response. PMID- 26856818 TI - Comprehensive behavioral phenotyping of a new Semaphorin 3 F mutant mouse. AB - BACKGROUND: Semaphorin 3 F (Sema3F) is a secreted type of the Semaphorin family of axon guidance molecules. Sema3F and its receptor neuropilin-2 (Npn-2) are expressed in a mutually exclusive manner in the embryonic mouse brain regions including olfactory bulb, hippocampus, and cerebral cortex. Sema3F is thought to have physiological functions in the formation of neuronal circuitry and its refinement. However, functional roles of Sema3F in the brain remain to be clarified. Here, we examined behavioral effects of Sema3F deficiency through a comprehensive behavioral test battery in Sema3F knockout (KO) male mice to understand the possible functions of Sema3F in the brain. RESULTS: Male Sema3F KO and wild-type (WT) control mice were subjected to a battery of behavioral tests, including neurological screen, rotarod, hot plate, prepulse inhibition, light/dark transition, open field, elevated plus maze, social interaction, Porsolt forced swim, tail suspension, Barnes maze, and fear conditioning tests. In the open field test, Sema3F KO mice traveled shorter distance and spent less time in the center of the field than WT controls during the early testing period. In the light/dark transition test, Sema3F KO mice also exhibited decreased distance traveled, fewer number of transitions, and longer latency to enter the light chamber compared with WT mice. In addition, Sema3F KO mice traveled shorter distance than WT mice in the elevated plus maze test, although there were no differences between genotypes in open arm entries and time spent in open arms. Similarly, Sema3F KO mice showed decreased distance traveled in the social interaction test. Sema3F KO mice displayed reduced immobility in the Porsolt forced swim test whereas there was no difference in immobility between genotypes in the tail suspension test. In the fear conditioning test, Sema3F KO mice exhibited increased freezing behavior when exposed to a conditioning context and an altered context in absence of a conditioned stimulus. In the tests for assessing motor function, pain sensitivity, startle response to an acoustic stimulus, sensorimotor gating, or spatial reference memory, there were no significant behavioral differences between Sema3F KO and WT mice. CONCLUSIONS: These results suggest that Sema3F deficiency induces decreased locomotor activity and possibly abnormal anxiety-related behaviors and also enhances contextual memory and generalized fear in mice. Thus, our findings suggest that Sema3F plays important roles in the development of neuronal circuitry underlying the regulation of some aspects of anxiety and fear responses. PMID- 26856820 TI - St Gallen molecular subtypes in screening-detected and symptomatic breast cancer in a prospective cohort with long-term follow-up. AB - BACKGROUND: Diagnosis by screening mammography is considered an independent positive prognostic factor, although the data are not fully in agreement. The aim of the study was to explore whether the mode of detection (screening-detected versus symptomatic) adds prognostic information to the St Gallen molecular subtypes of primary breast cancer, in terms of 10-year cumulative breast cancer mortality (BCM). METHODS: A prospective cohort of patients with primary breast cancer, who had regularly been invited to screening mammography, were included. Tissue microarrays were constructed from primary tumours and lymph node metastases, and evaluated by two independent pathologists. Primary tumours and lymph node metastases were classified into St Gallen molecular subtypes. Cause of death was retrieved from the Central Statistics Office. RESULTS: A total of 434 patients with primary breast cancer were included in the study. Some 370 primary tumours and 111 lymph node metastases were classified into St Gallen molecular subtypes. The luminal A-like subtype was more common among the screening-detected primary tumours (P = 0.035) and corresponding lymph node metastases (P = 0.114) than among symptomatic cancers. Patients with screening-detected tumours had a lower BCM (P = 0.017), and for those diagnosed with luminal A-like tumours the 10 year cumulative BCM was 3 per cent. For patients with luminal A-like lymph node metastases, there was no BCM. In a stepwise multivariable analysis, the prognostic information yielded by screening detection was hampered by stage and tumour biology. CONCLUSION: The prognosis was excellent for patients within the screening programme who were diagnosed with a luminal A-like primary tumour and/or lymph node metastases. Stage, molecular pathology and mode of detection help to define patients at low risk of death from breast cancer. PMID- 26856821 TI - The effect of ketogenic diet in an animal model of autism induced by prenatal exposure to valproic acid. AB - OBJECTIVES: Autism spectrum disorder (ASD) is characterized by impairments in social interaction and communication, and by restricted repetitive behaviors and interests. Its etiology is still unknown, but different environmental factors during pregnancy, such as exposure to valproic acid (VPA), are associated with high incidence of ASD in children. In this context, prenatal exposure to VPA in rodents has been used as a reliable model of ASD. Ketogenic diet (KD) is an alternative therapeutic option for refractory epilepsy; however, the effects of this approach in ASD-like behavior need to be evaluated. We conducted a behavioral assessment of the effects of KD in the VPA model of autism. METHODS: Pregnant animals received a single-intraperitoneal injection of 600 mg/kg VPA, and their offspring were separated into four groups: (1) control group with standard diet (C-SD), (2) control group with ketogenic diet (C-KD), (3) VPA group with standard diet (VPA-SD), and (4) VPA group with ketogenic diet (VPA-KD). RESULTS: When compared with the control group, VPA animals presented increased social impairment, repetitive behavior and higher nociceptive threshold. Interestingly, the VPA group fed with KD presented improvements in social behavior. These mice displayed higher scores in sociability index and social novelty index when compared with the SD-fed VPA mice. DISCUSSION: VPA mice chronically exposed to a KD presented behavioral improvements; however, the mechanism by which KD improves ASD-like features needs to be further investigated. In conclusion, the present study reinforces the potential use of KD as a treatment for the core deficits of ASD. PMID- 26856823 TI - Erratum. PMID- 26856822 TI - XRF-measured bone lead (Pb) as a biomarker for Pb exposure and toxicity among children diagnosed with Pb poisoning. AB - Childhood lead (Pb) poisoning remains a global issue, especially in industrial areas. In this study, 115 children with average age 5.7 years were recruited as either patient diagnosed with Pb poisoning or controls at Xinhua Hospital in China. The subjects' bone Pb was measured with a K-shell X-ray fluorescence (KXRF) and a portable X-ray fluorescence (XRF) system. A significant correlation between KXRF bone Pb and blood Pb and portable XRF and KXRF measurements were observed. The half-life of blood-lead was calculated to be 9.96 +/- 3.92 d. Our results indicate that bone is a useful biomarker for Pb in children. PMID- 26856824 TI - Removal of Dolutegravir by Hemodialysis in HIV-Infected Patients with End-Stage Renal Disease. AB - Data on dolutegravir removal by hemodialysis are lacking. To study this, we measured dolutegravir plasma concentrations in samples of blood entering and leaving the dialyzer and of the resulting dialysate from 5 HIV-infected patients with end-stage renal disease. The median dolutegravir hemodialysis extraction ratio was 7%. The dolutegravir concentrations after the dialysis session remained far above the protein-binding-adjusted inhibitory concentration. Our results show minimal dolutegravir removal by hemodialysis, with no specific dolutegravir dosage adjustments required in this setting. (This study is registered at ClinicalTrials.gov under registration number NCT02487706.). PMID- 26856825 TI - Antimicrobial Activities of Ceftaroline and Comparator Agents against Bacterial Organisms Causing Bacteremia in Patients with Skin and Skin Structure Infections in U.S. Medical Centers, 2008 to 2014. AB - We evaluated the antimicrobial susceptibility of 1,454 organisms consecutively collected from patients with bacteremia associated with skin and skin structure infections. The most common organisms obtained wereStaphylococcus aureus(670 organisms [46.1%]),Escherichia coli(200 organisms [13.8%]), beta-hemolytic streptococci (betaHS) (138 organisms [9.5%]), andKlebsiella pneumoniae(109 organisms [7.5%]). The susceptibility rates for ceftaroline were 97.9% forS. aureus(95.9% among methicillin-resistantS. aureus[MRSA]), 100.0% for betaHS, 86.5% forE. coli, and 89.0% forK. pneumoniae Ceftaroline and tigecycline provided the best overall coverage. PMID- 26856826 TI - Old Clinical Isolates of Acinetobacter seifertii in Brazil Producing OXA-58. PMID- 26856827 TI - Escape Mutations in NS4B Render Dengue Virus Insensitive to the Antiviral Activity of the Paracetamol Metabolite AM404. AB - Despite the enormous disease burden associated with dengue virus infections, a licensed antiviral drug is lacking. Here, we show that the paracetamol (acetaminophen) metabolite AM404 inhibits dengue virus replication. Moreover, we find that mutations in NS4B that were previously found to confer resistance to the antiviral compounds NITD-618 and SDM25N also render dengue virus insensitive to AM404. Our work provides further support for NS4B as a direct or indirect target for antiviral drug development. PMID- 26856829 TI - Assessment of the Worldwide Antimalarial Resistance Network Standardized Procedure for In Vitro Malaria Drug Sensitivity Testing Using SYBR Green Assay for Field Samples with Various Initial Parasitemia Levels. AB - The malaria SYBR green assay, which is used to profilein vitrodrug susceptibility ofPlasmodium falciparum, is a reliable drug screening and surveillance tool. Malaria field surveillance efforts provide isolates with various low levels of parasitemia. To be advantageous, malaria drug sensitivity assays should perform reproducibly among various starting parasitemia levels rather than at one fixed initial value. We examined the SYBR green assay standardized procedure developed by the Worldwide Antimalarial Resistance Network (WWARN) for its sensitivity and ability to accurately determine the drug concentration that inhibits parasite growth by 50% (IC50) in samples with a range of initial parasitemia levels. The initial sensitivity determination of the WWARN procedure yielded a detection limit of 0.019% parasitemia.P. falciparumlaboratory strains and field isolates with various levels of initial parasitemia were then subjected to a range of doses of common antimalarials. The IC50s were comparable for laboratory strains with between 0.0375% and 0.6% parasitemia and for field isolates with between 0.075% and 0.6% parasitemia for all drugs tested. Furthermore, assay quality (Z') analysis indicated that the WWARN procedure displays high robustness, allowing for drug testing of malaria field samples within the derived range of initial parasitemia. The use of the WWARN procedure should allow for the inclusion of more malaria field samples in malaria drug sensitivity screens that would have otherwise been excluded due to low initial parasitemia levels. PMID- 26856828 TI - Effects of Low-Dose Amoxicillin on Staphylococcus aureus USA300 Biofilms. AB - Previous studies showed that sub-MIC levels of beta-lactam antibiotics stimulate biofilm formation in most methicillin-resistant Staphylococcus aureus (MRSA) strains. Here, we investigated this process by measuring the effects of sub-MIC amoxicillin on biofilm formation by the epidemic community-associated MRSA strain USA300. We found that sub-MIC amoxicillin increased the ability of USA300 cells to attach to surfaces and form biofilms under both static and flow conditions. We also found that USA300 biofilms cultured in sub-MIC amoxicillin were thicker, contained more pillar and channel structures, and were less porous than biofilms cultured without antibiotic. Biofilm formation in sub-MIC amoxicillin correlated with the production of extracellular DNA (eDNA). However, eDNA released by amoxicillin-induced cell lysis alone was evidently not sufficient to stimulate biofilm. Sub-MIC levels of two other cell wall-active agents with different mechanisms of action-d-cycloserine and fosfomycin-also stimulated eDNA-dependent biofilm, suggesting that biofilm formation may be a mechanistic adaptation to cell wall stress. Screening a USA300 mariner transposon library for mutants deficient in biofilm formation in sub-MIC amoxicillin identified numerous known mediators of S. aureus beta-lactam resistance and biofilm formation, as well as novel genes not previously associated with these phenotypes. Our results link cell wall stress and biofilm formation in MRSA and suggest that eDNA-dependent biofilm formation by strain USA300 in low-dose amoxicillin is an inducible phenotype that can be used to identify novel genes impacting MRSA beta-lactam resistance and biofilm formation. PMID- 26856830 TI - In Vitro and In Vivo Trypanosomicidal Action of Novel Arylimidamides against Trypanosoma cruzi. AB - Arylimidamides (AIAs) have been shown to have considerable biological activity against intracellular pathogens, includingTrypanosoma cruzi, which causes Chagas disease. In the present study, the activities of 12 novel bis-AIAs and 2 mono AIAs against different strains ofT. cruziin vitroandin vivowere analyzed. The most active wasm-terphenyl bis-AIA (35DAP073), which had a 50% effective concentration (EC50) of 0.5 MUM for trypomastigotes (Y strain), which made it 26 fold more effective than benznidazole (Bz; 13 MUM). It was also active against the Colombiana strain (EC50= 3.8 MUM). Analysis of the activity against intracellular forms of the Tulahuen strain showed that this bis-AIA (EC50= 0.04 MUM) was about 100-fold more active than Bz (2 MUM). The trypanocidal effect was dissociated from the ability to trigger intracellular lipid bodies within host cells, detected by oil red labeling. Both an active compound (35DAP073) and an inactive compound (26SMB060) displayed similar activation profiles. Due to their high selectivity indexes, two AIAs (35DAP073 and 35DAP081) were moved toin vivostudies, but because of the results of acute toxicity assays, 35DAP081 was excluded from the subsequent tests. The findings obtained with 35DAP073 treatment of infections caused by the Y strain revealed that 2 days of therapy induced a dose-dependent action, leading to 96 to 46% reductions in the level of parasitemia. However, the administration of 10 daily doses in animals infected with the Colombiana strain resulted in toxicity, preventing longer periods of treatment. The activity of the combination of 0.5 mg/kg of body weight/day 35DAP073 with 100 mg/kg/day Bz for 10 consecutive days was then assayed. Treatment with the combination resulted in the suppression of parasitemia, the elimination of neurological toxic effects, and survival of 100% of the animals. Quantitative PCR showed a considerable reduction in the parasite load (60%) compared to that achieved with Bz or the amidine alone. Our results support further investigations of this class with the aim of developing novel alternatives for the treatment of Chagas disease. PMID- 26856831 TI - Landscape of Resistance-Nodulation-Cell Division (RND)-Type Efflux Pumps in Enterobacter cloacae Complex. AB - In Gram-negative bacteria, the active efflux is an important mechanism of antimicrobial resistance, but little is known about theEnterobacter cloacaecomplex (ECC). It is mediated primarily by pumps belonging to the RND (resistance-nodulation-cell division) family, and only AcrB, part of the AcrAB TolC tripartite system, was characterized in ECC. However, detailed genome sequence analysis of the strainE. cloacaesubsp.cloacaeATCC 13047 revealed to us that 10 other genes putatively coded for RND-type transporters. We then characterized the role of all of these candidates by construction of corresponding deletion mutants, which were tested for their antimicrobial susceptibility to 36 compounds, their virulence in the invertebrateGalleria mellonellamodel of infection, and their ability to form biofilm. Only the DeltaacrBmutant displayed significantly different phenotypes compared to that of the wild-type strain: 4- to 32-fold decrease of MICs of several antibiotics, antiseptics, and dyes, increased production of biofilm, and attenuated virulence inG. mellonella In order to identify specific substrates of each pump, we individually expressed intransall operons containing an RND pump-encoding gene into the DeltaacrBhypersusceptible strain. We showed that three other RND-type efflux systems (ECL_00053-00055, ECL_01758-01759, and ECL_02124-02125) were able to partially restore the wild-type phenotype and to superadd to and even enlarge the broad range of antimicrobial resistance. This is the first global study assessing the role of all RND efflux pumps chromosomally encoded by the ECC, which confirms the major role of AcrB in both pathogenicity and resistance and the potential involvement of other RND-type members in acquired resistance. PMID- 26856832 TI - Comprehensive Screening for Naturally Occurring Hepatitis C Virus Resistance to Direct-Acting Antivirals in the NS3, NS5A, and NS5B Genes in Worldwide Isolates of Viral Genotypes 1 to 6. AB - There is no comprehensive study available on the natural hepatitis C virus (HCV) polymorphism in sites associated with resistance including all viral genotypes which may present variable susceptibilities to particular direct-acting antivirals (DAAs). This study aimed to analyze the frequencies, genetic barriers, and evolutionary histories of naturally occurring resistance-associated variants (RAVs) in the six main HCV genotypes. A comprehensive analysis of up to 103 RAVs was performed in 2,901, 2,216, and 1,344 HCV isolates for the NS3, NS5A, and NS5B genes, respectively. We report significant intergenotypic differences in the frequencies of natural RAVs for these three HCV genes. In addition, we found a low genetic barrier for the generation of new RAVs, irrespective of the viral genotype. Furthermore, in 1,126 HCV genomes, including sequences spanning the three genes, haplotype analysis revealed a remarkably high frequency of viruses carrying more than one natural RAV to DAAs (53% of HCV-1a, 28.5% of HCV-1b, 67.1% of HCV-6, and 100% of genotype 2, 3, 4, and 5 haplotypes). With the exception of HCV-1a, the most prevalent haplotypes showed RAVs in at least two different viral genes. Finally, evolutionary analyses revealed that, while most natural RAVs appeared recently, others have been efficiently transmitted over time and cluster in well-supported clades. In summary, and despite the observed high efficacy of DAA-based regimens, we show that naturally occurring RAVs are common in all HCV genotypes and that there is an overall low genetic barrier for the selection of resistance mutations. There is a need for natural DAA resistance profiling specific for each HCV genotype. PMID- 26856835 TI - Novel Structures and Temporal Changes of Arginine Catabolic Mobile Elements in Methicillin-Resistant Staphylococcus aureus Genotypes ST5-MRSA-II and ST764-MRSA II in Japan. AB - Twenty-two of 1,103 methicillin-resistant Staphylococcus aureus (MRSA) isolates containing the type II staphylococcal cassette chromosome mec element (SCCmec) (collected in Hokkaido, Japan, from 2008 to 2011) harbored the arginine catabolic mobile element (ACME). Five genetic variations were identified in the ACME staphylococcal cassette chromosome mec composite islands, 66 to 79 kb in size. The percentage of ACME carriage temporally increased from 0.85% to 4.5% in parallel with the emergence of shorter variants (66 to 72 kb). Shorter variants may have a selective advantage and accelerate the dissemination of ACME in Japanese MRSA. PMID- 26856834 TI - VraH Is the Third Component of the Staphylococcus aureus VraDEH System Involved in Gallidermin and Daptomycin Resistance and Pathogenicity. AB - In bacteria, extracellular signals are transduced into the cell predominantly by two-component systems (TCSs) comprising a regulatory unit triggered by a specific signal. Some of the TCSs control executing units such as ABC transporters involved in antibiotic resistance. For instance, inStaphylococcus aureus, activation of BraSR leads to the upregulation ofvraDEexpression that encodes an ABC transporter playing a role in bacitracin and nisin resistance. In this study, we show that the small staphylococcal transmembrane protein VraH forms, together with VraDE, a three-component system. Although the expression ofvraHin the absence ofvraDEwas sufficient to mediate low-level resistance, only this VraDEH entity conferred high-level resistance against daptomycin and gallidermin. In most staphylococcal genomes,vraHis located immediately downstream ofvraDE, forming an operon, whereas in some species it is localized differently. In an invertebrate infection model, VraDEH significantly enhancedS. aureuspathogenicity. In analogy to the TCS connectors, VraH can be regarded as an ABC connector that modulates the activity of ABC transporters involved in antibiotic resistance. PMID- 26856833 TI - Kinetic Study of Laboratory Mutants of NDM-1 Metallo-beta-Lactamase and the Importance of an Isoleucine at Position 35. AB - Two laboratory mutants of NDM-1 were generated by replacing the isoleucine at position 35 with threonine and serine residues: the NDM-1(I35T)and NDM 1(I35S)enzymes. These mutants were well characterized, and their kinetic parameters were compared with those of the NDM-1 wild type. Thekcat,Km, andkcat/Kmvalues calculated for the two mutants were slightly different from those of the wild-type enzyme. Interestingly, thekcat/Kmof NDM-1(I35S)for loracarbef was about 14-fold higher than that of NDM-1. Far-UV circular dichroism (CD) spectra of NDM-1 and NDM-1(I35T)and NDM-1(I35S)enzymes suggest local structural rearrangements in the secondary structure with a marked reduction of alpha-helix content in the mutants. PMID- 26856836 TI - Dissecting the Structure-Function Relationship of a Fungicidal Peptide Derived from the Constant Region of Human Immunoglobulins. AB - Synthetic peptides encompassing sequences related to the complementarity determining regions of antibodies or derived from their constant region (Fc peptides) were proven to exert differential antimicrobial, antiviral, antitumor, and/or immunomodulatory activitiesin vitroand/orin vivo, regardless of the specificity and isotype of the parental antibody. Alanine substitution derivatives of these peptides exhibited unaltered, increased, or decreased candidacidal activitiesin vitro The bioactive IgG-derived Fc N10K peptide (NQVSLTCLVK) spontaneously self-assembles, a feature previously recognized as relevant for the therapeutic activity of another antibody-derived peptide. We evaluated the contribution of each residue to the peptide self-assembling capability by circular-dichroism spectroscopy. The interaction of the N10K peptide and its derivatives withCandida albicanscells was studied by confocal, transmission, and scanning electron microscopy. The apoptosis and autophagy induction profiles in yeast cells treated with the peptides were evaluated by flow cytometry, and the therapeutic efficacy against candidal infection was studied in aGalleria mellonellamodel. Overall, the results indicate a critical role for some residues in the self-assembly process and a correlation of that capability with the candidacidal activities of the peptidesin vitroand their therapeutic effectsin vivo. PMID- 26856837 TI - Rapid Emergence and Evolution of Staphylococcus aureus Clones Harboring fusC Containing Staphylococcal Cassette Chromosome Elements. AB - The prevalence of fusidic acid (FA) resistance amongStaphylococcus aureusstrains in New Zealand (NZ) is among the highest reported globally, with a recent study describing a resistance rate of approximately 28%. Three FA-resistantS. aureusclones (ST5 MRSA, ST1 MSSA, and ST1 MRSA) have emerged over the past decade and now predominate in NZ, and in all three clones FA resistance is mediated by thefusCgene. In particular, ST5 MRSA has rapidly become the dominant MRSA clone in NZ, although the origin of FA-resistant ST5 MRSA has not been explored, and the genetic context offusCin FA-resistant NZ isolates is unknown. To better understand the rapid emergence of FA-resistantS. aureus, we used population-based comparative genomics to characterize a collection of FA-resistant and FA susceptible isolates from NZ. FA-resistant NZ ST5 MRSA displayed minimal genetic diversity and represented a phylogenetically distinct clade within a global population model of clonal complex 5 (CC5)S. aureus In all lineages,fusCwas invariably located within staphylococcal cassette chromosome (SCC) elements, suggesting that SCC-mediated horizontal transfer is the primary mechanism offusCdissemination. The genotypic association offusCwithmecAhas important implications for the emergence of MRSA clones in populations with high usage of fusidic acid. In addition, we found thatfusCwas colocated with a recently described virulence factor (tirS) in dominant NZS. aureusclones, suggesting a fitness advantage. This study points to the likely molecular mechanisms responsible for the successful emergence and spread of FA-resistantS. aureus. PMID- 26856838 TI - Derivation and Multicenter Validation of the Drug Resistance in Pneumonia Clinical Prediction Score. AB - The health care-associated pneumonia (HCAP) criteria have a limited ability to predict pneumonia caused by drug-resistant bacteria and favor the overutilization of broad-spectrum antibiotics. We aimed to derive and validate a clinical prediction score with an improved ability to predict the risk of pneumonia due to drug-resistant pathogens compared to that of HCAP criteria. A derivation cohort of 200 microbiologically confirmed pneumonia cases in 2011 and 2012 was identified retrospectively. Risk factors for pneumonia due to drug-resistant pathogens were evaluated by logistic regression, and a novel prediction score (the drug resistance in pneumonia [DRIP] score) was derived. The score was then validated in a prospective, observational cohort of 200 microbiologically confirmed cases of pneumonia at four U.S. centers in 2013 and 2014. The DRIP score (area under the receiver operator curve [AUROC], 0.88 [95% confidence interval {CI}, 0.82 to 0.93]) performed significantly better (P = 0.02) than the HCAP criteria (AUROC, 0.72 [95% CI, 0.64 to 0.79]). At a threshold of >=4 points, the DRIP score demonstrated a sensitivity of 0.82 (95% CI, 0.67 to 0.88), a specificity of 0.81 (95% CI, 0.73 to 0.87), a positive predictive value (PPV) of 0.68 (95% CI, 0.56 to 0.78), and a negative predictive value (NPV) of 0.90 (95% CI, 0.81 to 0.93). By comparison, the performance of HCAP criteria was less favorable: sensitivity was 0.79 (95% CI, 0.67 to 0.88), specificity was 0.65 (95% CI, 0.56 to 0.73), PPV was 0.53 (95% CI, 0.42 to 0.63), and NPV was 0.86 (95% CI, 0.77 to 0.92). The overall accuracy of the HCAP criteria was 69.5% (95% CI, 62.5 to 75.7%), whereas that of the DRIP score was 81.5% (95% CI, 74.2 to 85.6%) (P = 0.005). Unnecessary extended-spectrum antibiotics were recommended 46% less frequently by applying the DRIP score (25/200, 12.5%) than by use of HCAP criteria (47/200, 23.5%) (P = 0.004), without increasing the rate at which inadequate treatment recommendations were made. The DRIP score was more predictive of the risk of pneumonia due to drug-resistant pathogens than HCAP criteria and may have the potential to decrease antibiotic overutilization in patients with pneumonia. Validation in larger cohorts of patients with pneumonia due to all causes is necessary. PMID- 26856840 TI - Antimicrobial Resistance in Salmonella in the United States from 1948 to 1995. AB - We conducted a retrospective study of 2,149 clinicalSalmonellastrains to help document the historical emergence of antimicrobial resistance. There were significant increases in resistance to older drugs, including ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, and tetracycline, which were most common inSalmonella entericaserotype Typhimurium. An increase in multidrug resistance was observed for each decade since the 1950s. These data help show howSalmonellaevolved over the past 6 decades, after the introduction of new antimicrobial agents. PMID- 26856839 TI - Association of Novel Nonsynonymous Single Nucleotide Polymorphisms in ampD with Cephalosporin Resistance and Phylogenetic Variations in ampC, ampR, ompF, and ompC in Enterobacter cloacae Isolates That Are Highly Resistant to Carbapenems. AB - InEnterobacter cloacae, the genetic lesions associated with derepression of the AmpC beta-lactamase include diverse single nucleotide polymorphisms (SNPs) and/or indels in theampDandampRgenes and SNPs inampC, while diverse SNPs in the promoter region or SNPs/indels within the coding sequence of outer membrane proteins have been described to alter porin production leading to carbapenem resistance. We sought to define the underlying mechanisms conferring cephalosporin and carbapenem resistance in a collection ofE. cloacaeisolates with unusually high carbapenem resistance and no known carbapenemase and, in contrast to many previous studies, considered the SNPs we detected in relation to the multilocus sequence type (MLST)-based phylogeny of our collection. Whole-genome sequencing was applied on the most resistant isolates to seek novel carbapenemases, expression ofampCwas measured by reverse transcriptase PCR, and porin translation was detected by SDS-PAGE. SNPs occurring inampC,ampR,ompF, andompCgenes (and their promoter regions) were mostly phylogenetic variations, relating to the isolates' sequence types, whereas nonsynonymous SNPs inampDwere associated with derepression of AmpC and cephalosporin resistance. The additional loss of porins resulted in high-level carbapenem resistance, underlining the clinical importance of chromosomal mutations among carbapenem-resistantE. cloacae. PMID- 26856842 TI - Delayed Onset of Plasmodium falciparum Malaria after Doxycycline Prophylaxis in a Soldier Returning from the Central African Republic. PMID- 26856843 TI - Molecular Characterization of Escherichia coli Strains Isolated from Retail Meat That Harbor blaCTX-M and fosA3 Genes. AB - A total of 55 cefotaxime-resistantEscherichia coliisolates were obtained from retail meat products purchased in Shenzhen, China, during the period November 2012 to May 2013. Thirty-seven of these 55 isolates were found to harbor ablaCTX Mgene, with theblaCTX-M-1group being the most common type.blaCMY-2was detected in 16 isolates, alone or in combination with other extended-spectrum beta-lactamase (ESBL) determinants. Importantly, thefosA3gene, which encodes fosfomycin resistance, was detected in 12 isolates, with several being found to reside in the conjugative plasmid that harbored theblaCTX-Mgene. The insertion sequence IS26was observed upstream of some of theblaCTX-M-55andfosA3genes. Conjugation experiments showed thatblaCTX-Mgenes from 15 isolates were transferrable, with Inc I1 and Inc FII being the most prevalent replicons. High clonal diversity was observed among theblaCTX-Mproducers, suggesting that horizontal transfer of theblaCTX-Mgenes amongE. colistrains in retail meats is a common event and that such strains may constitute an important reservoir ofblaCTX-Mgenes, which may be readily disseminated to other potential human pathogens. PMID- 26856844 TI - Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism. AB - Benznidazole (Bz), the drug used for treatment of Chagas' disease (caused by the protozoan Trypanosoma cruzi), is activated by a parasitic NADH-dependent type I nitroreductase (NTR I). However, several studies have shown that other enzymes are involved. The aim of this study was to evaluate whether the aldo-keto reductase from T. cruzi (TcAKR), a NADPH-dependent oxido-reductase previously described by our group, uses Bz as the substrate. We demonstrated that both recombinant and native TcAKR enzymes reduce Bz by using NADPH, but not NADH, as a cofactor. TcAKR-overexpressing epimastigotes showed higher NADPH-dependent Bz reductase activity and a 50% inhibitory concentration (IC50) value for Bz 1.8 fold higher than that of the controls, suggesting that TcAKR is involved in Bz detoxification instead of activation. To understand the role of TcAKR in Bz metabolism, we studied TcAKR expression and NADPH/NADH-dependent Bz reductase activities in two T. cruzi strains with differential susceptibility to Bz: CL Brener and Nicaragua. Taking into account the results obtained with TcAKR overexpressing epimastigotes, we expected the more resistant strain, Nicaragua, to have higher TcAKR levels than CL Brener. However, the results were the opposite. CL Brener showed 2-fold higher TcAKR expression and 5.7-fold higher NADPH-Bz reduction than the Nicaragua strain. In addition, NADH-dependent Bz reductase activity, characteristic of NTR I, was also higher in CL Brener than in Nicaragua. We conclude that although TcAKR uses Bz as the substrate, TcAKR activity is not a determinant of Bz resistance in wild-type strains and may be overcome by other enzymes involved in Bz activation, such as NADPH- and NADH dependent reductases. PMID- 26856841 TI - Optimizing the Clinical Use of Vancomycin. AB - The increasing number of infections produced by beta-lactam-resistant Gram positive bacteria and the morbidity secondary to these infections make it necessary to optimize the use of vancomycin. In 2009, the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Disease Pharmacists published specific guidelines about vancomycin dosage and monitoring. However, these guidelines have not been updated in the past 6 years. This review analyzes the new available information about vancomycin published in recent years regarding pharmacokinetics and pharmacodynamics, serum concentration monitoring, and optimal vancomycin dosing in special situations (obese people, burn patients, renal replacement therapy, among others). Vancomycin efficacy is linked to a correct dosage which should aim to reach an area under the curve (AUC)/MIC ratio of >=400; serum trough levels of 15 to 20 mg/liter are considered a surrogate marker of an AUC/MIC ratio of >=400 for a MIC of <=1 mg/liter. For Staphylococcus aureus strains presenting with a MIC >1 mg/liter, an alternative agent should be considered. Vancomycin doses must be adjusted according to body weight and the plasma trough levels of the drug. Nephrotoxicity has been associated with target vancomycin trough levels above 15 mg/liter. Continuous infusion is an option, especially for patients at high risk of renal impairment or unstable vancomycin clearance. In such cases, vancomycin plasma steady-state level and creatinine monitoring are strongly indicated. PMID- 26856845 TI - Low Concentrations of Nitric Oxide Modulate Streptococcus pneumoniae Biofilm Metabolism and Antibiotic Tolerance. AB - Streptococcus pneumoniaeis one of the key pathogens responsible for otitis media (OM), the most common infection in children and the largest cause of childhood antibiotic prescription. Novel therapeutic strategies that reduce the overall antibiotic consumption due to OM are required because, although widespread pneumococcal conjugate immunization has controlled invasive pneumococcal disease, overall OM incidence has not decreased. Biofilm formation represents an important phenotype contributing to the antibiotic tolerance and persistence ofS. pneumoniaein chronic or recurrent OM. We investigated the treatment of pneumococcal biofilms with nitric oxide (NO), an endogenous signaling molecule and therapeutic agent that has been demonstrated to trigger biofilm dispersal in other bacterial species. We hypothesized that addition of low concentrations of NO to pneumococcal biofilms would improve antibiotic efficacy and that higher concentrations exert direct antibacterial effects. Unlike in many other bacterial species, low concentrations of NO did not result inS. pneumoniaebiofilm dispersal. Instead, treatment of bothin vitrobiofilms andex vivoadenoid tissue samples (a reservoir forS. pneumoniaebiofilms) with low concentrations of NO enhanced pneumococcal killing when combined with amoxicillin-clavulanic acid, an antibiotic commonly used to treat chronic OM. Quantitative proteomic analysis using iTRAQ (isobaric tag for relative and absolute quantitation) identified 13 proteins that were differentially expressed following low-concentration NO treatment, 85% of which function in metabolism or translation. Treatment with low concentration NO, therefore, appears to modulate pneumococcal metabolism and may represent a novel therapeutic approach to reduce antibiotic tolerance in pneumococcal biofilms. PMID- 26856846 TI - Multicenter Prospective Cohort Study of Renal Failure in Patients Treated with Colistin versus Polymyxin B. AB - Nephrotoxicity is the main adverse effect of colistin and polymyxin B (PMB). It is not clear whether these two antibiotics are associated with different nephrotoxicity rates. We compared the incidences of renal failure (RF) in patients treated with colistimethate sodium (CMS) or PMB for >=48 h. A multicenter prospective cohort study was performed that included patients aged >=18 years. The primary outcome was renal failure (RF) according to Risk, Injury, Failure, Loss, and End-stage renal disease (RIFLE) criteria. Multivariate analysis with a Cox regression model was performed. A total of 491 patients were included: 81 in the CMS group and 410 in the PMB group. The mean daily doses in milligrams per kilogram of body weight were 4.2 +/- 1.3 and 2.4 +/- 0.73 of colistin base activity and PMB, respectively. The overall incidence of RF was 16.9% (83 patients): 38.3% and 12.7% in the CMS and PMB groups, respectively (P< 0.001). In multivariate analysis, CMS therapy was an independent risk factor for RF (hazard ratio, 3.35; 95% confidence interval, 2.05 to 5.48;P< 0.001) along with intensive care unit admission, higher weight, older age, and bloodstream and intraabdominal infections. CMS was also independently associated with a higher risk of RF in various subgroup analyses. The incidence of RF was higher in the CMS group regardless of the patient baseline creatinine clearance. The development of RF during therapy was not associated with 30-day mortality in multivariate analysis. CMS was associated with significantly higher rates of RF than those of PMB. Further studies are required to confirm our findings in other patient populations. PMID- 26856847 TI - Novel Engineered Peptides of a Phage Lysin as Effective Antimicrobials against Multidrug-Resistant Acinetobacter baumannii. AB - Acinetobacter baumannii is a Gram-negative bacterial pathogen responsible for a range of nosocomial infections. The recent rise and spread of multidrug-resistant A. baumannii clones has fueled a search for alternative therapies, including bacteriophage endolysins with potent antibacterial activities. A common feature of these lysins is the presence of a highly positively charged C-terminal domain with a likely role in promoting outer membrane penetration. In the present study, we show that the C-terminal amino acids 108 to 138 of phage lysin PlyF307, named P307, alone were sufficient to kill A. baumannii (>3 logs). Furthermore, P307 could be engineered for improved activity, the most active derivative being P307SQ-8C (>5-log kill). Both P307 and P307SQ-8C showed high in vitro activity against A. baumannii in biofilms. Moreover, P307SQ-8C exhibited MICs comparable to those of levofloxacin and ceftazidime and acted synergistically with polymyxin B. Although the peptides were shown to kill by disrupting the bacterial cytoplasmic membrane, they did not lyse human red blood cells or B cells; however, serum was found to be inhibitory to lytic activity. In a murine model of A. baumannii skin infection, P307SQ-8C reduced the bacterial burden by ~2 logs in 2 h. This study demonstrates the prospect of using peptide derivatives from bacteriophage lysins to treat topical infections and remove biofilms caused by Gram-negative pathogens. PMID- 26856849 TI - Lead Selection of a New Aminomethylphenol, JPC-3210, for Malaria Treatment and Prevention. AB - Structure-activity relationship studies of trifluoromethyl-substituted pyridine and pyrimidine analogues of 2-aminomethylphenols (JPC-2997, JPC-3186, and JPC 3210) were conducted for preclinical development for malaria treatment and/or prevention. Of these compounds, JPC-3210 [4-(tert-butyl)-2-((tert butylamino)methyl)-6-(5-fluoro-6-(trifluoromethyl)pyridin-3-yl)phenol] was selected as the lead compound due to superior in vitro antimalarial activity against multidrug-resistant Plasmodium falciparum lines, lower in vitro cytotoxicity in mammalian cell lines, longer plasma elimination half-life, and greater in vivo efficacy against murine malaria. PMID- 26856850 TI - Endobronchial metastases of colorectal cancer. AB - Colorectal metastases affecting trachea or bronchi are highly unusual. Up to 26% of endotracheal/endobronchial metastases are due to colorectal cancer. Treatment and palliative management rely on a multidisciplinary team to improve their quality of life. PMID- 26856848 TI - Screening of a Library of FDA-Approved Drugs Identifies Several Enterovirus Replication Inhibitors That Target Viral Protein 2C. AB - Enteroviruses (EVs) represent many important pathogens of humans. Unfortunately, no antiviral compounds currently exist to treat infections with these viruses. We screened the Prestwick Chemical Library, a library of approved drugs, for inhibitors of coxsackievirus B3, identified pirlindole as a potent novel inhibitor, and confirmed the inhibitory action of dibucaine, zuclopenthixol, fluoxetine, and formoterol. Upon testing of viruses of several EV species, we found that dibucaine and pirlindole inhibited EV-B and EV-D and that dibucaine also inhibited EV-A, but none of them inhibited EV-C or rhinoviruses (RVs). In contrast, formoterol inhibited all enteroviruses and rhinoviruses tested. All compounds acted through the inhibition of genome replication. Mutations in the coding sequence of the coxsackievirus B3 (CV-B3) 2C protein conferred resistance to dibucaine, pirlindole, and zuclopenthixol but not formoterol, suggesting that 2C is the target for this set of compounds. Importantly, dibucaine bound to CV-B3 protein 2C in vitro, whereas binding to a 2C protein carrying the resistance mutations was reduced, providing an explanation for how resistance is acquired. PMID- 26856851 TI - Cloning, expression, and characterization of a thermostable glucose-6-phosphate dehydrogenase from Thermoanaerobacter tengcongensis. AB - Glucose-6-phosphate dehydrogenases (G6PDs) are important enzymes widely used in bioassay and biocatalysis. In this study, we reported the cloning, expression, and enzymatic characterization of G6PDs from the thermophilic bacterium Thermoanaerobacter tengcongensis MB4 (TtG6PD). SDS-PAGE showed that purified recombinant enzyme had an apparent subunit molecular weight of 60 kDa. Kinetics assay indicated that TtG6PD preferred NADP(+) (k cat/K m = 2618 mM(-1) s(-1), k cat = 249 s(-1), K m = 0.10 +/- 0.01 mM) as cofactor, although NAD(+) (k cat/K m = 138 mM(-1) s(-1), k cat = 604 s(-1), K m = 4.37 +/- 0.56 mM) could also be accepted. The K m values of glucose-6-phosphate were 0.27 +/- 0.07 mM and 5.08 +/ 0.68 mM with NADP(+) and NAD(+) as cofactors, respectively. The enzyme displayed its optimum activity at pH 6.8-9.0 for NADP(+) and at pH 7.0-8.6 for NAD(+) while the optimal temperature was 80 degrees C for NADP(+) and 70 degrees C for NAD(+). This was the first observation that the NADP(+)-linked optimal temperature of a dual coenzyme-specific G6PD was higher than the NAD(+)-linked and growth (75 degrees C) optimal temperature, which suggested G6PD might contribute to the thermal resistance of a bacterium. The potential of TtG6PD to measure the activity of another thermophilic enzyme was demonstrated by the coupled assays for a thermophilic glucokinase. PMID- 26856852 TI - Blunted neuroactive steroid and HPA axis responses to stress are associated with reduced sleep quality and negative affect in pregnancy: a pilot study. AB - RATIONALE: Anxiety during pregnancy has been linked to adverse maternal health outcomes, including postpartum depression (PPD). However, there has been limited study of biological mechanisms underlying behavioral predictors of PPD during pregnancy. OBJECTIVES: Considering the shared etiology of chronic stress amongst antenatal behavioral predictors, the primary goal of this pilot study was to examine associations among stress-related physiological factors (including GABA ergic neurosteroids) and stress-related behavioral indices of anxiety during pregnancy. METHODS: Fourteen nulliparous women in their second trimester of a singleton pregnancy underwent speech and mental arithmetic stress, following a 2 week subjective and objective recording of sleep-wake behavior. RESULTS: Lower cortisol, progesterone, and a combined measure of ALLO + pregnanolone throughout the entire stressor protocol (area under the curve, AUC) were associated with greater negative emotional responses to stress, and lower cortisol AUC was associated with worse sleep quality. Lower adrenocorticotropic hormone was associated with greater anxious and depressive symptoms. Stress produced paradoxical reductions in cortisol, progesterone, and a combined measure of allopregnanolone + pregnanolone, while tetrahydrodeoxycorticosterone levels were elevated. CONCLUSIONS: These data suggest that cortisol, progesterone, and ALLO + pregnanolone levels in the second trimester of pregnancy are inversely related to negative emotional symptoms, and the negative impact of acute stress challenge appears to exert its effects by reducing these steroids to further promote negative emotional responses. PMID- 26856853 TI - Repeated administration of the 5-HT1B/1A agonist, RU 24969, facilitates the acquisition of MDMA self-administration: role of 5-HT1A and 5-HT1B receptor mechanisms. AB - RATIONALE: 3,4 Methylenedioxymethamphetamine (MDMA) preferentially stimulates the release of serotonin (5-HT) that subsequently produces behavioral responses by activation of post-synaptic receptor mechanisms. The 5-HT1A and 5-HT1B receptors are both well localized to regulate dopamine (DA) release, and have been implicated in modulating the reinforcing effects of many drugs of abuse, but a role in acquisition of self-administration has not been determined. OBJECTIVES: This study was designed to determine the effect of pharmacological manipulation of 5-HT1A and 5-HT1B receptor mechanisms on the acquisition of MDMA self administration. METHODS: The 5-HT1B/1A receptor agonist, RU 24969 (0.0 or 3.0 mg/kg, bid), was administered for 3 days in order to down-regulate both 5-HT1A and 5-HT1B receptors. Following the pretreatment phase, latency to acquisition of MDMA self-administration was measured. RESULTS: Repeated administration of RU 24969 significantly decreased the latency to acquisition and increased the proportion of animals that acquired MDMA self-administration. Dose-effect curves for the 5-HT1A-mediated hyperactivity produced by the 5-HT1A agonist, 8-OH-DPAT, and the 5-HT1B-mediated adipsic response produced by RU 24969 were shifted rightward, suggesting a desensitization of 5-HT1A and 5-HT1B receptor mechanisms. CONCLUSIONS: These data suggest that the initial reinforcing effects of MDMA are modulated by 5-HT1A and/or 5-HT1B receptor mechanisms. The potential impact of these changes on the DAergic response relevant to self-administration and a possible role in conditioned reinforcement pertaining to acquisition of self administration are discussed. PMID- 26856854 TI - MDMA self-administration fails to alter the behavioral response to 5-HT(1A) and 5 HT(1B) agonists. AB - RATIONALE: Regular use of the street drug, ecstasy, produces a number of cognitive and behavioral deficits. One possible mechanism for these deficits is functional changes in serotonin (5-HT) receptors as a consequence of prolonged 3,4 methylenedioxymethamphetamine (MDMA)-produced 5-HT release. Of particular interest are the 5-HT(1A) and 5-HT(1B) receptor subtypes since they have been implicated in several of the behaviors that have been shown to be impacted in ecstasy users and in animals exposed to MDMA. OBJECTIVES: This study aimed to determine the effect of extensive MDMA self-administration on behavioral responses to the 5-HT(1A) agonist, 8-hydroxy-2-(n-dipropylamino)tetralin (8-OH DPAT), and the 5-HT(1B/1A) agonist, RU 24969. METHODS: Male Sprague-Dawley rats self-administered a total of 350 mg/kg MDMA, or vehicle, over 20-58 daily self administration sessions. Two days after the last self-administration session, the hyperactive response to 8-OH-DPAT (0.03-1.0 mg/kg) or the adipsic response to RU 24969 (0.3-3.0 mg/kg) were assessed. RESULTS: 8-OH-DPAT dose dependently increased horizontal activity, but this response was not altered by MDMA self administration. The dose-response curve for RU 24969-produced adipsia was also not altered by MDMA self-administration. CONCLUSIONS: Cognitive and behavioral deficits produced by repeated exposure to MDMA self-administration are not likely due to alterations in 5-HT(1A) or 5-HT(1B) receptor mechanisms. PMID- 26856855 TI - Alterations in behavioral responses to dopamine agonists in olfactory bulbectomized mice: relationship to changes in the striatal dopaminergic system. AB - BACKGROUND: Olfactory bulbectomy (OBX) in rodents is considered a putative animal model of depression. It has been reported that some abnormal behaviors observed in this animal model of depression involve dopaminergic neurons of the mesolimbic pathway. Therefore, we examined changes in the dopaminergic system in the caudate putamen (CPu), nucleus accumbens core (NAcC), and shell (NAcSh) of OBX mice and whether or not these alterations were reversed by chronic administration of imipramine. METHODS: We observed climbing behavior, which is a dopamine (DA) receptor-associated behavior, to demonstrate changes in the dopaminergic system of the mesolimbic pathway, when mice were administrated either the nonselective DA agonist apomorphine only or were pre-treated with the selective D1 antagonist SCH23390, with the selective D2 antagonist sulpiride, or with the D2/D3 partial agonist aripiprazole (ARI). Moreover, we examined tyrosine hydroxylase (TH) and D1- and D2-like receptor levels in the CPu, NAcC, and NAcSh using immunohistochemistry and autoradiography. RESULTS: The OBX group exhibited significantly enhanced apomorphine-induced climbing behavior, and this enhanced behavior was reversed by administration of sulpiride, ARI, and imipramine but not SCH23390. Moreover, we found a reduction in TH levels in the CPu, NAcC, and NAcSh of OBX mice and an increase in D2 receptor densities in the NAcC of OBX mice. The increased D2 receptor density observed in OBX mice was reversed by imipramine administration. CONCLUSIONS: These findings reveal that OBX mice display enhanced DA receptor responsiveness, which may relate to some of the behavioral abnormalities reported in this animal model. PMID- 26856856 TI - Successful human epidermal growth receptor 2-targeted therapy beyond disease progression for extramammary Paget's disease. AB - Extramammary Paget's disease is a malignant intraepithelial carcinoma, which constitutes less than 1 % of all vulvar malignancies. Surgical resection is the first treatment of choice and standard chemotherapy has not been established for advanced or recurrent disease. Experimental and clinical studies have identified human epidermal growth receptor 2 as a potential therapeutic target. A 63-year old male was referred for recurrent extramammary Paget's disease after surgery. Human epidermal growth receptor 2 was shown to be overexpressed and amplified by immunohistochemical analysis and fluorescence in situ hybridization analysis, respectively. After two cycles of trastuzumab monotherapy, all lymph node metastases decreased in size. However, he experienced recurrence in the lymph nodes during the seven courses of trastuzumab. As a subsequent treatment, trastuzumab was administered in combination with docetaxel and pertuzumab; clinical response was sustained for 12 months without significant adverse events. PMID- 26856857 TI - Similar age-dependent levothyroxine requirements of schoolchildren with congenital or acquired hypothyroidism. AB - A recent study in children suggested that levothyroxine requirements are higher in congenital than in acquired hypothyroidism but did not match for severity of disease. Here, we studied only children with congenital or acquired hypothyroidism who had an undetectable fT4 at diagnosis. There were eight girls with congenital hypothyroidism due to athyreosis and eight girls with acquired hypothyroidism due to autoimmune thyroid disease. The median levothyroxine dose received at the most recent visit when serum TSH was <5.0 mU/L (at a median age of 7.86 and 14.29 years, respectively) was 3.2 mcg/kg/day in the former and 2.4 mcg/kg/day in the latter (N.S.). Combining both groups, the levothyroxine requirement decreased by 0.5 mcg/kg/day for every 4-year period. CONCLUSION: When strictly matched for severity of disease, levothyroxine requirements are similar in school-age children with congenital or acquired hypothyroidism and decrease with age. Thus, in congenital hypothyroidism treated early with high-dose levothyroxine, pituitary resistance to thyroxine feedback does not appear to be present at school age. WHAT IS KNOWN: * Pediatric studies unmatched for severity have suggested that levothyroxine requirements are higher in congenital than in acquired hypothyroidism. What is new: * When strictly matched for severity, levothyroxine requirements are similar in children with congenital or acquired hypothyroidism and decrease with age. PMID- 26856858 TI - Rib fractures after reirradiation plus hyperthermia for recurrent breast cancer: Predictive factors. AB - BACKGROUND: Combining reirradiation (reRT) and hyperthermia (HT) has shown high therapeutic value for patients with locoregional recurrent breast cancer (LR). However, additional toxicity of reirradiation (e.g., rib fractures) may occur. The aim of this study is to determine the impact of potential risk factors on the occurrence of rib fractures. PATIENTS AND METHODS: From 1982-2005, 234 patients were treated with adjuvant reRT + HT after surgery for LR. ReRT consisted typically of 8 fractions of 4 Gy twice a week, or 12 fractions of 3 Gy four times a week. A total of 118 patients were irradiated with abutted photon and electron fields. In all, 60 patients were irradiated using either one or alternating combinations of abutted AP electron fields. Hyperthermia was given once or twice a week. RESULTS: The 5-year infield local control (LC) rate was 70 %. Rib fractures were detected in 16 of 234 patients (actuarial risk: 7 % at 5 years). All rib fractures occurred in patients treated with a combination of photon and abutted electron fields (p = 0.000); in 15 of 16 patients fractures were located in the abutment regions. The other significant predictive factors for rib fractures were a higher fraction dose (p = 0.040), large RT fields, and treatment before the year 2000. DISCUSSION AND CONCLUSION: ReRT + HT results in long-term LC. The majority of rib fractures were located in the photon/electron abutment area, emphasizing the disadvantage of field overlap. Large abutted photon/electron fields combined with 4 Gy fractions increase the number of rib fractures in this study group. However, as these factors were highly correlated no relative importance of the individual factors could be estimated. Increasing the number of HT sessions a week does not increase the risk of rib fractures. PMID- 26856859 TI - Crocin protects the liver and kidney from patulin-induced apoptosis in vivo. AB - Patulin (PAT) is a mycotoxin mainly produced by Aspergillus, Penicillium, and Bissochlamys. Given the high risk associated with this mycotoxin, its potential effects have been investigated by many studies. It is known to be teratogenic, mutagenic, and genotoxic, and it has been shown to induce damages in several organs in experimental animals. Our aim was to investigate the preventive effect against PAT-induced apoptosis in vivo using natural carotenoid, Crocin (CRO). Mice were divided into six groups: a control group, a "PAT alone" group, a "CRO alone" group, and a "PAT plus CRO" groups (pre-treatment conditions). Our results showed that CRO restored the normal levels of biochemical parameters in the liver and kidney. The analysis of the protein expression in these organs revealed that PAT-induced toxicity promotes the induction of apoptosis via the increase in P53, Bax, and cytochrome C and the decrease in Bcl2 expressions. We also found that PAT triggered caspase 3 activation and DNA fragmentation. However, pre-treatment with CRO demonstrated a reduction in the induction of apoptosis via the regulation of all tested biomarkers demonstrating that CRO is effective in the protection against PAT hazards. This could be relevant, particularly with the emergent demand for natural products which may counteract the detrimental toxic effects and therefore prevents multiple human diseases. PMID- 26856860 TI - Effects of calcium supplementation on growth and biochemistry in two passerine species breeding in a Ca-poor and metal-polluted area. AB - Several studies provide evidence of calcium (Ca)-limited reproduction in birds. A Ca-supplementation experiment was carried out in 2014 in a Ca-poor area associated with metal pollution in SW Finland. We aimed to evaluate the relationship between Ca availability and heavy metal exposure in free-living passerines, and to compare Ca levels in plasma and feces and the effects of Ca supplementation and metals on breeding, nestling growth, and plasma biochemistry in great tits and pied flycatchers. Although the Ca supplement was used by parents, in general the treatment had limited effects on growth and biochemistry, suggesting that parents are capable of finding sufficient Ca-rich foods to allow nestlings to grow properly. Snail shells were an abundant Ca source in the moderately polluted zone for pied flycatcher, and great tits likely combines the intake of snail shells and other anthropogenic Ca-rich items. Great tits had higher Ca concentrations in feces and plasma than pied flycatcher nestlings, suggesting that they need and sustain higher Ca levels and seem to be more opportunistic in search for Ca than pied flycatcher, since they consumed more of the supplemented Ca. Negative effects of pollution in nestling size and fledgling number were found in great tit. This species may suffer especially from the lower food quality and quantity in the polluted area. The pied flycatcher seems to be adapted to low Ca availability and they can successfully breed when metal concentrations are not too high. Our results show that great tits and pied flycatchers may employ different strategies in response to low Ca availability. PMID- 26856861 TI - Effect of zero valent iron nanoparticles to Eisenia fetida in three soil types. AB - In this study, the influence of soil types on the effect of the commercial form of C-nZVI on tissue concentrations, cellular component, reproduction outcome in Eisenia fetida, and the soil health was investigated. C-nZVI at concentration level of 3 g kg(-1) soil showed no effect on the survival of E. fetida in the three soil types. However, varying effects such as concentration-dependent increase in tissue iron concentration, lipid peroxidation, and damage to DNA molecules by C-nZVI were observed. C-nZVI at an exposure concentration of 60 mg kg(-1) soil induced oxidative stress in E. fetida. Tissue Fe concentration appeared correlated to the DNA damage. Oxidative stress and DNA damage may explain the toxicity mechanisms of nZVI to E. fetida. Graphical Abstract Reactive oxygen species induced by nZVI. PMID- 26856862 TI - Variations in the accumulation and translocation of cadmium among pak choi cultivars as related to root morphology. AB - A pot experiment was performed to investigate the variations in cadmium (Cd) accumulation among pak choi cultivars and its relationships to root morphology. The biomass, Cd accumulation and root morphology of 20 pak choi cultivars were determined in low and high Cd treatments. Significant variations in Cd accumulation and root morphological parameters were observed between pak choi cultivars. Cd concentrations in shoots differed between cultivars by a factor of 2.3 (13.3-30.8 MUg g(-1)) and 2.6 (35.5-94.0 MUg g(-1)) for low and high Cd treatments, respectively. The total Cd in plants positively correlated to the root length, root surface area, root volume, and root length/shoot biomass ratio in both Cd treatments. The shoot Cd concentration was also positively correlated with the root length, root surface area, and root length/shoot biomass ratio. Moreover, the proportion of fine roots (diameter less than 0.2 mm) was positively correlated with the total Cd in plants in low Cd treatment, and positively correlated with percentage of Cd in shoots in high Cd treatment. These results suggested that root morphology might be partially responsible for variation of Cd accumulation among pak choi cultivars. High Cd cultivars exhibit longer root length, greater root surface area, higher root volume, and a higher proportion of fine roots than low Cd cultivars. PMID- 26856863 TI - T-screen and yeast assay for the detection of the thyroid-disrupting activities of cadmium, mercury, and zinc. AB - In the present study, a two-hybrid yeast bioassay and a T-screen were used to screen for the thyroid receptor (TR)-disrupting activity of select metallic compounds (CdCl2, ZnCl2, HgCl2, CuSO4, MnSO4, and MgSO4). The results reveal that none of the tested metallic compounds showed TR-agonistic activity, whereas ZnCl2, HgCl2, and CdCl2 demonstrated TR antagonism. For the yeast assay, the dose response relationship of these metallic compounds was established, and the concentrations producing 20 % of the maximum effect of ZnCl2, HgCl2, and CdCl2 were 9.1 * 10(-5), 3.2 * 10(-6), and 1.2 * 10(-6) mol/L, respectively. The T screen also supported the finding that ZnCl2, HgCl2, and CdCl2 decreased the cell proliferation at concentrations ranging from 10(-6) to 10(-4) mol/L. Furthermore, the thyroid-disrupting activity of metallic compounds in environmental water samples collected from the Guanting Reservoir, Beijing, China was evaluated. Solid-phase extraction was used to separate the organic extracts, and a modified two-hybrid yeast bioassay revealed that the metallic compounds in the water samples could affect thyroid hormone-induced signaling by decreasing the binding of the thyroid hormone. The addition of ethylenediaminetetraacetic acid (30 mg/L) could eliminate the effects. Thus, the cause(s) of the thyroid toxicity in the water samples appeared to be partly related to the metallic compounds. PMID- 26856864 TI - Effects of glyphosate on hepatic tissue evaluating melanomacrophages and erythrocytes responses in neotropical anuran Leptodactylus latinasus. AB - Glyphosate (GLY) is the most used herbicide worldwide and its effects on anurans are well known. Pollutants can cause physiological and morphological effects. Therefore, this study evaluated the effects of GLY on hepatic melanomacrophages as a response to environmental stressors. Three treatments were exposed to different concentrations of pure GLY (100, 1000, and 10,000 MUg g(-1), respectively), and there was also a control group. After the experimental time, liver and blood were analyzed. Melanomacrophages (MMCs) were located between the hepatocyte cordons, close to sinusoids. GLY increased the melanin area in MMCs of Leptodactylus latinasus exposed since lowest concentration until highest concentration. GLY also changed the occurrence of hepatic catabolism pigments into melanomacrophages and erythrocyte nuclear abnormalities; therefore, it can interfere with the hepatic metabolism. In conclusion, GLY promotes alterations in the hepatic tissue and erythrocyte nuclear abnormalities. Furthermore, MMCs may be useful as morphological responses of GLY effects. PMID- 26856865 TI - Underestimating neonicotinoid exposure: how extent and magnitude may be affected by land-use change. AB - Potential detrimental impacts of neonicotinoids on non-target organisms, especially bees, have been subject to a wide debate and the subsequent ban of three neonicotinoids by the EU. While recent research has fortified concerns regarding the effects of neonicotinoids on ecosystem service (ES) providers, potential impacts have been considered negligible in systems with a relatively small proportion of arable land and thus lower the use of these pesticides. In this paper we argue that there is not sufficient information to assess magnitude and extent of neonicotinoid application, as well as potential non-target impacts on ES providers in grass-dominated systems with frequent land-use change. Using Ireland as an example, we show that the highly dynamic agricultural landscape, in conjunction with estimated persistence times of neonicotinoids in soils, may lead to a much larger area (18.6 +/- 0.6% of the Irish agricultural area) exposed to these pesticides than initially assumed. Furthermore we present a number of important gaps in current research regarding the impacts of neonicotinoids on ES providers in such systems. PMID- 26856866 TI - Simultaneous nitrification and denitrification in a novel membrane bioelectrochemical reactor with low membrane fouling tendency. AB - Microbial fuel cells (MFCs) can use nitrate as a cathodic electron acceptor for electrochemical denitrification, yet there is little knowledge about how to apply them into current wastewater treatment process to achieve efficient nitrogen removal. In this study, two dual-chamber MFCs were integrated with an aerobic membrane bioreactor to construct a novel membrane bioelectrochemical reactor (MBER) for simultaneous nitrification and denitrification under specific aeration. The effects of chemical oxygen demand (COD) loading rate, COD/N ratio, hydraulic retention time (HRT), and external resistance on the system performance were investigated. High effluent quality was obtained in the MBER in terms of COD and ammonium. During the operation, denitrification simultaneously occurred with nitrification at the bio-cathode of the MBER, achieving a maximal nitrogen removal efficiency of 84.3 %. A maximum power density of 1.8 W/m3 and a current density of 8.5 A/m3 were achieved with a coulombic efficiency of 12.1 %. Furthermore, compared to the control system, the MBER exhibited lower membrane fouling tendency due to mixed liquor volatile suspended solids (MLVSSs) and extracellular polymeric substance (EPS) reductions, EPSp/EPSc ratio decrease, and particle size increase of the sludge. These results suggest that the MBER holds potential for efficient nitrogen removal, electricity production, and membrane fouling mitigation. PMID- 26856868 TI - Assessment of sediment quality based on acid-volatile sulfide and simultaneously extracted metals in heavily industrialized area of Asaluyeh, Persian Gulf: concentrations, spatial distributions, and sediment bioavailability/toxicity. AB - Sediment samples from the coastal area of Asaluyeh harbor were collected during autumn and spring 2015. The acid-volatile sulfide (AVS) and simultaneously extracted metals (SEMs) were measured to assess the sediment quality and potential ecological risks. The average concentrations (and relative standard deviation (RSD)) of AVS in the industrial sediments were 12.32 MUmol/g (36.91) and 6.34 MUmol/g (80.05) in autumn and spring, respectively, while in the urban area, these values were 0.44 MUmol/g (123.50) and 0.31 MUmol/g (160.0) in autumn and spring, respectively. The average concentrations of SEM (and RSD) in the industrial sediments were 15.02 MUmol/g (14.38) and 12.34 MUmol/g (20.65) in autumn and spring, respectively, while in the urban area, these values were 1.10 MUmol/g (43.03) and 1.06 MUmol/g (55.59) in autumn and spring, respectively. Zn was the predominant component (34.25-86.24 %) of SEM, while the corresponding value for Cd, much more toxic ingredient, was less than 1 %. Some of the coastal sediments in the harbor of Asaluyeh (20 and 47 % in autumn and spring, respectively) had expected adverse biological effects based on the suggested criterion by United States Environmental Protection Agency (USEPA), while most stations (80 and 53 % in autumn and spring, respectively) had uncertain adverse effects. PMID- 26856869 TI - Land spreading of sewage sludge in forest plantations: effects on the growth of the duckweed Lemna minor and trace metal bioaccumulation in the snail Cantareus aspersus. AB - Wastewater plants generated annually millions of tons of sewage sludge (SS). Large amounts of this organic residue are spread on agricultural lands as a fertilizer, although it is viewed as a major potential source of contamination, presenting a danger to the terrestrial and aquatic environments. This study was undertaken to evaluate the impact of this practice on the duckweed Lemna minor and the snail Cantareus aspersus. Sludge was applied to soil either at six different loading rates equal to 0, 0.4, 3, 10, 30, and 60 tons dry matter (DM) ha(-1) for L. minor test or at three rates equal to 0, 30, and 60 tons DM ha(-1) for C. aspersus test. At the highest rate of SS application (60 tons DM ha(-1)), the eluates showed that an increase in pH (6.1) resulted in a decrease in Al levels. Thus, the high stimulation of L. minor growth observed after this high rate of SS application can be explained by (i) a reduction in Al toxicity after precipitation and (ii) macro- and micronutrient enrichment. At a rate of SS application of only 30 tons DM ha(-1), growth appeared to be slightly significant (p < 0.05), in spite of the significant increase in essential mineral elements. However, it is very difficult to discriminate between Al toxicity and pH effects. For the test with C. aspersus, the snail biomass was not affected by sludge application over the exposure period. Mortality was extremely low, with a rate of less than 4 % at the last sampling date. Yet, Cu, Pb, and Cd accumulated significantly in the soft body of snails exposed to SS application, suggesting that the amount of metals excreted is lower than that absorbed. In contrast, Zn levels remain constant, inferring that absorption and elimination of Zn are balanced at the beginning of the experiment. PMID- 26856870 TI - Performance analysis and optimization of an advanced pharmaceutical wastewater treatment plant through a visual basic software tool (PWWT.VB). AB - A user-friendly, menu-driven simulation software tool has been developed for the first time to optimize and analyze the system performance of an advanced continuous membrane-integrated pharmaceutical wastewater treatment plant. The software allows pre-analysis and manipulation of input data which helps in optimization and shows the software performance visually on a graphical platform. Moreover, the software helps the user to "visualize" the effects of the operating parameters through its model-predicted output profiles. The software is based on a dynamic mathematical model, developed for a systematically integrated forward osmosis-nanofiltration process for removal of toxic organic compounds from pharmaceutical wastewater. The model-predicted values have been observed to corroborate well with the extensive experimental investigations which were found to be consistent under varying operating conditions like operating pressure, operating flow rate, and draw solute concentration. Low values of the relative error (RE = 0.09) and high values of Willmott-d-index (d will = 0.981) reflected a high degree of accuracy and reliability of the software. This software is likely to be a very efficient tool for system design or simulation of an advanced membrane-integrated treatment plant for hazardous wastewater. PMID- 26856867 TI - Human bronchial epithelial cells exposed in vitro to diesel exhaust particles exhibit alterations in cell rheology and cytotoxicity associated with decrease in antioxidant defenses and imbalance in pro- and anti-apoptotic gene expression. AB - Diesel exhaust particles (DEPs) from diesel engines produce adverse alterations in cells of the airways by activating intracellular signaling pathways and apoptotic gene overexpression, and also by influencing metabolism and cytoskeleton changes. This study used human bronchial epithelium cells (BEAS-2B) in culture and evaluates their exposure to DEPs (15ug/mL for 1 and 2 h) in order to determine changes to cell rheology (viscoelasticity) and gene expression of the enzymes involved in oxidative stress, apoptosis, and cytotoxicity. BEAS-2B cells exposed to DEPs were found to have a significant loss in stiffness, membrane stability, and mitochondrial activity. The genes involved in apoptosis [B cell lymphoma 2 (BCL-2 and caspase-3)] presented inversely proportional expressions (p = 0.05, p = 0.01, respectively), low expression of the genes involved in antioxidant responses [SOD1 (superoxide dismutase 1); SOD2 (superoxide dismutase 2), and GPx (glutathione peroxidase) (p = 0.01)], along with an increase in cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) (p = 0.01). These results suggest that alterations in cell rheology and cytotoxicity could be associated with oxidative stress and imbalance between pro- and anti-apoptotic genes. PMID- 26856872 TI - Stable water layers on solid surfaces. AB - Liquid layers adhered to solid surfaces and that are in equilibrium with the vapor phase are common in printing, coating, and washing processes as well as in alveoli in lungs and in stomata in leaves. For such a liquid layer in equilibrium with the vapor it faces, it has been generally believed that, aside from liquid lumps, only a very thin layer of the liquid, i.e., with a thickness of only a few nanometers, is held onto the surface of the solid, and that this adhesion is due to van der Waals forces. A similar layer of water can remain on the surface of a wall of a microchannel after evaporation of bulk water creates a void in the channel, but the thickness of such a water layer has not yet been well characterized. Herein we showed such a water layer adhered to a microchannel wall to be 100 to 170 nm thick and stable against surface tension. The water layer thickness was measured using electron energy loss spectroscopy (EELS), and the water layer structure was characterized by using a quantitative nanoparticle counting technique. This thickness was found for channel gap heights ranging from 1 to 5 MUm. Once formed, the water layers in the microchannel, when sealed, were stable for at least one week without any special care. Our results indicate that the water layer forms naturally and is closely associated only with the surface to which it adheres. Our study of naturally formed, stable water layers may shed light on topics from gas exchange in alveoli in biology to the post-wet-process control in the semiconductor industry. We anticipate our report to be a starting point for more detailed research and understanding of the microfluidics, mechanisms and applications of gas-liquid-solid systems. PMID- 26856871 TI - Reliable and cost-effective serodiagnosis of rheumatoid arthritis. AB - Early diagnosis of patients with rheumatoid arthritis (RA) optimises therapeutic benefit and the probability of achieving disease remission. Notwithstanding clinical acumen, early diagnosis is dependent on access to reliable serodiagnostic procedures, as well as on the discerning application and interpretation of these. In the case of RA, however, no disease-specific serodiagnostic procedure is available due to the multi-factorial and polygenic nature of this autoimmune disorder. This has resulted in the development of an array of serodiagnostic procedures based on the detection of autoantibodies reactive with various putative autoantigens. Other procedures based on measurement of elevations in the concentrations of systemic biomarkers of inflammation, most commonly acute phase reactants and cytokines/chemokines, are used as objective indices of disease activity. Following a brief overview of RA research in African populations, the current review is focused on those autoantibodies/biomarkers, specifically rheumatoid factor, anti-citrullinated peptide antibodies and C-reactive protein, which are currently recognised as being the most reliable and cost-effective with respect to disease prediction and diagnosis, as well as in monitoring activity and outcome. PMID- 26856874 TI - Three-dimensional visualization of arsenic stimulated mouse liver sinusoidal by FIB-SEM approach. PMID- 26856873 TI - Homocysteine activates T cells by enhancing endoplasmic reticulum-mitochondria coupling and increasing mitochondrial respiration. AB - Hyperhomocysteinemia (HHcy) accelerates atherosclerosis by increasing proliferation and stimulating cytokine secretion in T cells. However, whether homocysteine (Hcy)-mediated T cell activation is associated with metabolic reprogramming is unclear. Here, our in vivo and in vitro studies showed that Hcy stimulated splenic T-cell activation in mice was accompanied by increased levels of mitochondrial reactive oxygen species (ROS) and calcium, mitochondrial mass and respiration. Inhibiting mitochondrial ROS production and calcium signals or blocking mitochondrial respiration largely blunted Hcy-induced T-cell interferon gamma (IFN-gamma) secretion and proliferation. Hcy also enhanced endoplasmic reticulum (ER) stress in T cells, and inhibition of ER stress with 4 phenylbutyric acid blocked Hcy-induced T-cell activation. Mechanistically, Hcy increased ER-mitochondria coupling, and uncoupling ER-mitochondria by the microtubule inhibitor nocodazole attenuated Hcy-stimulated mitochondrial reprogramming, IFN-gamma secretion and proliferation in T cells, suggesting that juxtaposition of ER and mitochondria is required for Hcy-promoted mitochondrial function and T-cell activation. In conclusion, Hcy promotes T-cell activation by increasing ER-mitochondria coupling and regulating metabolic reprogramming. PMID- 26856875 TI - Providing English foreign language teachers with content knowledge to facilitate decoding and spelling acquisition: a longitudinal perspective. AB - This quasi-experimental study adds to the small existing literature on orthographic-related teacher knowledge in an English as a foreign language (EFL) context. The study examined the impact of a course on English orthography on predominantly non-native-speaking EFL preservice and inservice teachers' orthographic content knowledge, and the extent to which these teachers retained orthographic-related content knowledge four months after participating in a semester course on the topic. In addition, the study examined the relationship between participants' acquired orthographic-related content knowledge and EFL spelling. Both groups of teachers that studied in the course improved on overall orthographic-related content knowledge, both immediately following the course and longitudinally. Preservice and inservice participants showed similar levels of orthographic knowledge prior to course participation and both showed significant improvements compared to controls following course participation. Participants also retained knowledge four months after course completion. Overall, the inservice teachers scored higher on orthographic-related knowledge, possibly as a result of the immediate application of their newly acquired knowledge. An unexpected finding was a lack of interaction between acquired orthographic related content knowledge and pseudo word spelling scores. Possible methodological limitations, such as number of participants as well as the length and scope of the course, may explain this outcome. This paper also discusses practical implications of this study for EFL decoding and spelling instruction. PMID- 26856876 TI - Ceratomyxa bohari sp. n. (Myxozoa: Ceratomyxidae) from the gall bladder of Lutjanus bohar Forsskal from the Red Sea coast off Saudi Arabia: morphology, seasonality and SSU rDNA sequence. PMID- 26856877 TI - Selective and reversible suppression of intestinal stem cell differentiation by pharmacological inhibition of BET bromodomains. AB - Absorptive and secretory cells of the small intestine are derived from a single population of Lgr5-expressing stem cells. While key genetic pathways required for differentiation into specific lineages have been defined, epigenetic programs contributing to this process remain poorly characterized. Members of the BET family of chromatin adaptors contain tandem bromodomains that mediate binding to acetylated lysines on target proteins to regulate gene expression. In this study, we demonstrate that mice treated with a small molecule inhibitor of BET bromodomains, CPI203, exhibit greater than 90% decrease in tuft and enteroendocrine cells in both crypts and villi of the small intestine, with no changes observed in goblet or Paneth cells. BET bromodomain inhibition did not alter the abundance of Lgr5-expressing stem cells in crypts, but rather exerted its effects on intermediate progenitors, in part through regulation of Ngn3 expression. When BET bromodomain inhibition was combined with the chemotherapeutic gemcitabine, pervasive apoptosis was observed in intestinal crypts, revealing an important role for BET bromodomain activity in intestinal homeostasis. Pharmacological targeting of BET bromodomains defines a novel pathway required for tuft and enteroendocrine differentiation and provides an important tool to further dissect the progression from stem cell to terminally differentiated secretory cell. PMID- 26856879 TI - Stability of Household and Housing Characteristics Among Farmworker Families in North Carolina: Implications for Health. AB - Household and housing stability are important for health and well-being of individuals, particularly children. This analysis examines stability in household and housing over 2 years for North Carolina farmworker families with children. Mothers with a child aged 2-4 years in farmworker families (n = 248) completed interviews over 2 years. Household measures included number of adults and children, moves, and spouse absence. Housing measures included tenure, persons per bedroom, and kitchen facilities. Household and housing characteristics for participants retained in the study over 2 years (n = 221) were stable in number of persons, tenure, persons per bedroom, and kitchen facilities. Households were large with one-third having 3 or more adults, and one-quarter having 4 or more children. Most families rented houses (over 15 % owned), which were crowded. Participants lost to follow-up were similar to retained participants in household characteristics, but had worse housing characteristics. Comparative research on farmworker family household composition is needed. PMID- 26856881 TI - Bladder cancer: Could chemohyperthermia finally set the NMIBC world on fire? PMID- 26856882 TI - Erectile dysfunction: Vardenafil in men with T2DM. PMID- 26856880 TI - Changing expression profiles of lncRNAs, mRNAs, circRNAs and miRNAs during osteoclastogenesis. AB - Bone is a dynamic organ continuously undergoing shaping, repairing and remodeling. The homeostasis of bone is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts (OCs) are specialized multinucleated cells derived from hematopoietic stem cells (HSCs) or monocytes/macrophage progenitor cells. There are different stages during osteoclastogenesis, and one of the most important steps to form functional osteoclasts is realized by cell-cell fusion. In our study, microarray was performed to detect the expression profiles of lncRNA, mRNA, circRNA and miRNA at different stages during osteoclastogenesis of RAW264.7 cells. Often changed RNAs were selected and clustered among the four groups with Venn analysis. The results revealed that expressions of 518 lncRNAs, 207 mRNAs, 24 circRNAs and 37 miRNAs were often altered at each stage during OC differentiation. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis were performed to predict the functions of differentially expressed lncRNAs and co-expressed potential targeting genes. Co-expression networks of lncRNA-mRNA and circRNA-miRNA were constructed based on the correlation analysis between the differentially expressed RNAs. The present study provided a systematic perspective on the potential function of non-coding RNAs (ncRNAs) during osteoclastogenesis. PMID- 26856883 TI - Prostate cancer: The TRAPEZE swings for treatment results. PMID- 26856885 TI - Variability in Hospice Care at the Very End of Life. PMID- 26856884 TI - Development and application of a novel genome-wide SNP array reveals domestication history in soybean. AB - Domestication of soybeans occurred under the intense human-directed selections aimed at developing high-yielding lines. Tracing the domestication history and identifying the genes underlying soybean domestication require further exploration. Here, we developed a high-throughput NJAU 355 K SoySNP array and used this array to study the genetic variation patterns in 367 soybean accessions, including 105 wild soybeans and 262 cultivated soybeans. The population genetic analysis suggests that cultivated soybeans have tended to originate from northern and central China, from where they spread to other regions, accompanied with a gradual increase in seed weight. Genome-wide scanning for evidence of artificial selection revealed signs of selective sweeps involving genes controlling domestication-related agronomic traits including seed weight. To further identify genomic regions related to seed weight, a genome-wide association study (GWAS) was conducted across multiple environments in wild and cultivated soybeans. As a result, a strong linkage disequilibrium region on chromosome 20 was found to be significantly correlated with seed weight in cultivated soybeans. Collectively, these findings should provide an important basis for genomic-enabled breeding and advance the study of functional genomics in soybean. PMID- 26856886 TI - Efficient graphene saturable absorbers on D-shaped optical fiber for ultrashort pulse generation. AB - We demonstrated a method to construct high efficiency saturable absorbers based on the evanescent light field interaction of CVD monolayer graphene deposited on side-polished D-shaped optical fiber. A set of samples was fabricated with two different core-graphene distances (0 and 1 MUm), covered with graphene ranging between 10 and 25 mm length. The mode-locking was achieved and the best pulse duration was 256 fs, the shortest pulse reported in the literature with CVD monolayer graphene in EDFL. As result, we find a criterion between the polarization relative extinction ratio in the samples and the pulse duration, which relates the better mode-locking performance with the higher polarization extinction ratio of the samples. This criterion also provides a better understanding of the graphene distributed saturable absorbers and their reproducible performance as optoelectronic devices for optical applications. PMID- 26856887 TI - Summaries for Patients. Mechanical Symptoms and Arthroscopic Partial Meniscectomy in Patients With Degenerative Meniscus Tear. PMID- 26856888 TI - Precise AuxPt1-x Alloy Nanoparticle Array of Tunable Composition for Catalytic Applications. AB - A 3-dimensional Block Copolymer Micellar nanoLithography (BCML) process was used to prepare AuxPt1-x alloy nanoparticles (NPs) monodisperse in size and composition, strongly anchored onto SiO2-particles (0.2 wt.% AuxPt1-x/SiO2). The particles possess a face-centered cubic (fcc) crystal structure and their size could be varied from 3-12 nm. We demonstrate the uniformity of the Au/Pt composition by analyzing individual NPs by energy-dispersive X-ray spectroscopy. The strongly bound AuxPt1-x NPs catalyzed the oxidation of CO with high activity. Thermal ageing experiments in pure CO2 as well as in ambient atmosphere demonstrated stability of the size distribution for times as long as 22 h. PMID- 26856889 TI - In Sickness but Not in Wealth: Field Evidence on Patients' Risk Preferences in Financial and Health Domains. AB - We present results from a hypothetical framed field experiment assessing whether risk preferences significantly differ across the health and financial domains when they are elicited through the same multiple price list paired-lottery method. We consider a sample of 300 patients attending outpatient clinics in a university hospital in Athens during the Greek financial crisis. Risk preferences in finance were elicited using paired-lottery questions with hypothetical payments. The questions were adapted to the health domain by framing the lotteries as risky treatments in hypothetical health care scenarios. Using maximum likelihood methods, we estimated the degree of risk aversion, allowing for the estimates to be dependent on domain and individual characteristics. The subjects in our sample, who were exposed to both health and financial distress, tended to be less risk averse in the financial domain than in the health domain. PMID- 26856891 TI - A mitochondrial-targeted ubiquinone modulates muscle lipid profile and improves mitochondrial respiration in obesogenic diet-fed rats. AB - The prevalence of the metabolic syndrome components including abdominal obesity, dyslipidaemia and insulin resistance is increasing in both developed and developing countries. It is generally accepted that the development of these features is preceded by, or accompanied with, impaired mitochondrial function. The present study was designed to analyse the effects of a mitochondrial-targeted lipophilic ubiquinone (MitoQ) on muscle lipid profile modulation and mitochondrial function in obesogenic diet-fed rats. For this purpose, twenty-four young male Sprague-Dawley rats were divided into three groups and fed one of the following diets: (1) control, (2) high fat (HF) and (3) HF+MitoQ. After 8 weeks, mitochondrial function markers and lipid metabolism/profile modifications in skeletal muscle were measured. The HF diet was effective at inducing the major features of the metabolic syndrome--namely, obesity, hepatic enlargement and glucose intolerance. MitoQ intake prevented the increase in rat body weight, attenuated the increase in adipose tissue and liver weights and partially reversed glucose intolerance. At the muscle level, the HF diet induced moderate TAG accumulation associated with important modifications in the muscle phospholipid classes and in the fatty acid composition of total muscle lipid. These lipid modifications were accompanied with decrease in mitochondrial respiration. MitoQ intake corrected the lipid alterations and restored mitochondrial respiration. These results indicate that MitoQ protected obesogenic diet-fed rats from some features of the metabolic syndrome through its effects on muscle lipid metabolism and mitochondrial activity. These findings suggest that MitoQ is a promising candidate for future human trials in the metabolic syndrome prevention. PMID- 26856892 TI - Restricted maternal nutrition alters myogenic regulatory factor expression in satellite cells of ovine offspring. AB - Poor maternal nutrition inhibits muscle development and postnatal muscle growth. Satellite cells are myogenic precursor cells that contribute to postnatal muscle growth, and their activity can be evaluated by the expression of several transcription factors. Paired-box (Pax)7 is expressed in quiescent and active satellite cells. MyoD is expressed in activated and proliferating satellite cells and myogenin is expressed in terminally differentiating cells. Disruption in the expression pattern or timing of expression of myogenic regulatory factors negatively affects muscle development and growth. We hypothesized that poor maternal nutrition during gestation would alter the in vitro temporal expression of MyoD and myogenin in satellite cells from offspring at birth and 3 months of age. Ewes were fed 100% or 60% of NRC requirements from day 31+/-1.3 of gestation. Lambs from control-fed (CON) or restricted-fed (RES) ewes were euthanized within 24 h of birth (birth; n=5) or were fed a control diet until 3 months of age (n=5). Satellite cells isolated from the semitendinosus muscle were used for gene expression analysis or cultured for 24, 48 or 72 h and immunostained for Pax7, MyoD or myogenin. Fusion index was calculated from a subset of cells allowed to differentiate. Compared with CON, temporal expression of MyoD and myogenin was altered in cultured satellite cells isolated from RES lambs at birth. The percent of cells expressing MyoD was greater in RES than CON (P=0.03) after 24 h in culture. After 48 h of culture, there was a greater percent of cells expressing myogenin in RES compared with CON (P0.05). In satellite cells from RES lambs at 3 months of age, the percent of cells expressing MyoD and myogenin were greater than CON after 72 h in culture (P<0.05). Fusion index was reduced in RES lambs at 3 months of age compared with CON (P<0.001). Restricted nutrition during gestation alters the temporal expression of myogenic regulatory factors in satellite cells of the offspring, which may reduce the pool of myoblasts, decrease myoblast fusion and contribute to the poor postnatal muscle growth previously observed in these animals. PMID- 26856890 TI - Relief of hypoxia by angiogenesis promotes neural stem cell differentiation by targeting glycolysis. AB - Blood vessels are part of the stem cell niche in the developing cerebral cortex, but their in vivo role in controlling the expansion and differentiation of neural stem cells (NSCs) in development has not been studied. Here, we report that relief of hypoxia in the developing cerebral cortex by ingrowth of blood vessels temporo-spatially coincided with NSC differentiation. Selective perturbation of brain angiogenesis in vessel-specific Gpr124 null embryos, which prevented the relief from hypoxia, increased NSC expansion at the expense of differentiation. Conversely, exposure to increased oxygen levels rescued NSC differentiation in Gpr124 null embryos and increased it further in WT embryos, suggesting that niche blood vessels regulate NSC differentiation at least in part by providing oxygen. Consistent herewith, hypoxia-inducible factor (HIF)-1alpha levels controlled the switch of NSC expansion to differentiation. Finally, we provide evidence that high glycolytic activity of NSCs is required to prevent their precocious differentiation in vivo Thus, blood vessel function is required for efficient NSC differentiation in the developing cerebral cortex by providing oxygen and possibly regulating NSC metabolism. PMID- 26856893 TI - Pax6 in Collembola: Adaptive Evolution of Eye Regression. AB - Unlike the compound eyes in insects, collembolan eyes are comparatively simple: some species have eyes with different numbers of ocelli (1 + 1 to 8 + 8), and some species have no apparent eye structures. Pax6 is a universal master control gene for eye morphogenesis. In this study, full-length Pax6 cDNAs, Fc-Pax6 and Cd Pax6, were cloned from an eyeless collembolan (Folsomia candida, soil-dwelling) and an eyed one (Ceratophysella denticulata, surface-dwelling), respectively. Their phylogenetic positions are between the two Pax6 paralogs in insects, eyeless (ey) and twin of eyeless (toy), and their protein sequences are more similar to Ey than to Toy. Both Fc-Pax6 and Cd-Pax6 could induce ectopic eyes in Drosophila, while Fc-Pax6 exhibited much weaker transactivation ability than Cd Pax6. The C-terminus of collembolan Pax6 is indispensable for its transactivation ability, and determines the differences of transactivation ability between Fc Pax6 and Cd-Pax6. One of the possible reasons is that Fc-Pax6 accumulated more mutations at some key functional sites of C-terminus under a lower selection pressure on eye development due to the dark habitats of F. candida. The composite data provide a first molecular evidence for the monophyletic origin of collembolan eyes, and indicate the eye degeneration of collembolans is caused by adaptive evolution. PMID- 26856895 TI - Multi-scale modelling of ovarian follicular development: From follicular morphogenesis to selection for ovulation. AB - In this review, we present multi-scale mathematical models of ovarian follicular development that are based on the embedding of physiological mechanisms into the cell scale. During basal follicular development, follicular growth operates through an increase in the oocyte size concomitant with the proliferation of its surrounding granulosa cells. We have developed a spatio-temporal model of follicular morphogenesis explaining how the interactions between the oocyte and granulosa cells need to be properly balanced to shape the follicle. During terminal follicular development, the ovulatory follicle is selected amongst a cohort of simultaneously growing follicles. To address this process of follicle selection, we have developed a model giving a continuous and deterministic description of follicle development, adapted to high numbers of cells and based on the dynamical and hormonally regulated repartition of granulosa cells into different cell states, namely proliferation, differentiation and apoptosis. This model takes into account the hormonal feedback loop involving the growing ovarian follicles and the pituitary gland, and enables the exploration of mechanisms regulating the number of ovulations at each ovarian cycle. Both models are useful for addressing ovarian physio-pathological situations. Moreover, they can be proposed as generic modelling environments to study various developmental processes and cell interaction mechanisms. PMID- 26856894 TI - Health Insurance and Health Care among the Mid-Aged and Older Chinese: Evidence from the National Baseline Survey of CHARLS. AB - We document the recent profile of health insurance and health care among mid-aged and older Chinese using data from the China Health and Retirement Longitudinal Study conducted in 2011. Overall health insurance coverage is about 93%. Multivariate regressions show that respondents with lower income as measured by per capita expenditure have a lower chance of being insured, as do the less educated, older, and divorced/widowed women and rural-registered people. Premiums and reimbursement rates of health insurance vary significantly by schemes. Inpatient reimbursement rates for urban people increase with total cost to a plateau of 60%; rural people receive much less. Demographic characteristics such as age, education, marriage status, per capita expenditure, and self-reported health status are not significantly associated with share of out-of-pocket cost after controlling community effects. For health service use, we find large gaps that vary across health insurance plans, especially for inpatient service. People with access to urban health insurance plans are more likely to use health services. In general, Chinese people have easy access to median low-level medical facilities. It is also not difficult to access general hospitals or specialized hospitals, but there exists better access to healthcare facilities in urban areas. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26856896 TI - Time for global action on Zika virus epidemic. PMID- 26856897 TI - Trajectories of childhood internalizing and externalizing psychopathology and psychotic-like experiences in adolescence: A prospective population-based cohort study. AB - Adolescent internalizing and externalizing psychopathology is strongly associated with adult psychiatric morbidity, including psychotic disorders. This study examined whether internalizing or externalizing trajectories (continuity/discontinuity of symptoms) from middle childhood were associated with adolescent psychotic-like experiences (PLEs). Prospective data were collected from a community sample of 553 children (mean age = 10.4 years; 50% male) and their primary caregivers. Participants completed questionnaire reports of internalizing and externalizing psychopathology and PLEs at baseline, and again approximately 2 years later. Logistic regression was used to examine the association of adolescent PLEs with four trajectories of internalizing and externalizing psychopathology (persistent, incident, remitting, and none), controlling for a range of potential confounders and sampling bias. Significant associations were identified between adolescent PLEs and the incident internalizing (adjusted odds ratio [adj. OR] = 2.96; 95% confidence interval [CI] = 1.60-5.49) and externalizing psychopathology (adj. OR = 2.14; 95% CI = 1.11 4.14) trajectories, as well as the persistent internalizing (adj. OR = 1.90; 95% CI = 1.13-3.18) and externalizing (adj. OR = 1.81, 95% CI = 1.02-3.19) trajectories. Children with remitting psychopathology trajectories were no more likely to present later PLEs than those who never experienced psychopathology. While for many individuals symptoms and illness remit during development without intervention, this study provides important insights regarding potential targets and timing for delivery of early intervention and prevention programs. PMID- 26856898 TI - Unihemispheric Sleep: An Enigma for Current Models of Sleep-Wake Regulation. PMID- 26856899 TI - The Cumulative Impact of Adolescent Sleep Loss: Next Steps. PMID- 26856900 TI - Hungry for Sleep: A Role for Endocannabinoids? PMID- 26856901 TI - Inter-individual Differences in the Effects of Aircraft Noise on Sleep Fragmentation. AB - STUDY OBJECTIVES: Environmental noise exposure disturbs sleep and impairs recuperation, and may contribute to the increased risk for (cardiovascular) disease. Noise policy and regulation are usually based on average responses despite potentially large inter-individual differences in the effects of traffic noise on sleep. In this analysis, we investigated what percentage of the total variance in noise-induced awakening reactions can be explained by stable inter individual differences. METHODS: We investigated 69 healthy subjects polysomnographically (mean +/- standard deviation 40 +/- 13 years, range 18-68 years, 32 male) in this randomized, balanced, double-blind, repeated measures laboratory study. This study included one adaptation night, 9 nights with exposure to 40, 80, or 120 road, rail, and/or air traffic noise events (including one noise-free control night), and one recovery night. RESULTS: Mixed-effects models of variance controlling for reaction probability in noise-free control nights, age, sex, number of noise events, and study night showed that 40.5% of the total variance in awakening probability and 52.0% of the total variance in EEG arousal probability were explained by inter-individual differences. If the data set was restricted to nights (4 exposure nights with 80 noise events per night), 46.7% of the total variance in awakening probability and 57.9% of the total variance in EEG arousal probability were explained by inter-individual differences. The results thus demonstrate that, even in this relatively homogeneous, healthy, adult study population, a considerable amount of the variance observed in noise-induced sleep disturbance can be explained by inter individual differences that cannot be explained by age, gender, or specific study design aspects. CONCLUSIONS: It will be important to identify those at higher risk for noise induced sleep disturbance. Furthermore, the custom to base noise policy and legislation on average responses should be re-assessed based on these findings. PMID- 26856902 TI - Hypocretin-1 Levels Associate with Fragmented Sleep in Patients with Narcolepsy Type 1. AB - STUDY OBJECTIVES: We aimed to analyze nocturnal sleep characteristics of patients with narcolepsy type 1 (narcolepsy with cataplexy) measured by actigraphy in respect to cerebrospinal fluid hypocretin-1 levels of the same patients. METHODS: Actigraphy recording of 1-2 w and hypocretin-1 concentration analysis were done to thirty-six unmedicated patients, aged 7 to 63 y, 50% female. Twenty-six of them had hypocretin-1 levels under 30 pg/mL and the rest had levels of 31-79 pg/mL. RESULTS: According to actigraphy, patients with very low hypocretin levels had statistically significantly longer sleep latency (P = 0.033) and more fragmented sleep, indicated by both the number of immobile phases of 1 min (P = 0.020) and movement + fragmentation index (P = 0.049). There were no statistically significant differences in the actual sleep time or circadian rhythm parameters measured by actigraphy. CONCLUSIONS: Actigraphy gives additional information about the stabilization of sleep in patients with narcolepsy type 1. Very low hypocretin levels associate with more wake intruding into sleep. PMID- 26856903 TI - Risk of Narcolepsy after AS03 Adjuvanted Pandemic A/H1N1 2009 Influenza Vaccine in Adults: A Case-Coverage Study in England. AB - STUDY OBJECTIVES: An increased risk of narcolepsy has been observed in children following ASO3-adjuvanted pandemic A/H1N1 2009 (Pandemrix) vaccine. We investigated whether this risk extends to adults in England. METHODS: Six adult sleep centers in England were visited between November 2012 and February 2014 and vaccination/clinical histories obtained from general practitioners. Suspected narcolepsy cases aged older than 17 y were selected. The risk of narcolepsy following Pandemrix was calculated using cases diagnosed by the time of the center visits and those with a diagnosis by November 30, 2011 after which there was increased awareness of the risk in children. The odds of vaccination in cases and in matched population data were compared using a case-coverage design. RESULTS: Of 1,446 possible cases identified, most had onset before 2009 or were clearly not narcolepsy. Of the 60 remaining cases, 20 were excluded after expert review, leaving 40 cases with narcolepsy; 5 had received Pandemrix between 3 and 18 mo before onset. All the vaccinated cases had cataplexy, two received a diagnosis by November 2011 and two were aged 40 y or older. The odds ratio for vaccination in cases compared to the population was 4.24 (95% confidence interval 1.45-12.38) using all cases and 9.06 (1.90-43.17) using cases with a diagnosis by November 2011, giving an attributable risk of 0.59 cases per 100,000 doses. CONCLUSIONS: We found a significantly increased risk of narcolepsy in adults following Pandemrix vaccination in England. The risk was lower than that seen in children using a similar study design. PMID- 26856904 TI - Responses in Rat Core Auditory Cortex are Preserved during Sleep Spindle Oscillations. AB - STUDY OBJECTIVES: Sleep is defined as a reversible state of reduction in sensory responsiveness and immobility. A long-standing hypothesis suggests that a high arousal threshold during non-rapid eye movement (NREM) sleep is mediated by sleep spindle oscillations, impairing thalamocortical transmission of incoming sensory stimuli. Here we set out to test this idea directly by examining sensory-evoked neuronal spiking activity during natural sleep. METHODS: We compared neuronal (n = 269) and multiunit activity (MUA), as well as local field potentials (LFP) in rat core auditory cortex (A1) during NREM sleep, comparing responses to sounds depending on the presence or absence of sleep spindles. RESULTS: We found that sleep spindles robustly modulated the timing of neuronal discharges in A1. However, responses to sounds were nearly identical for all measured signals including isolated neurons, MUA, and LFPs (all differences < 10%). Furthermore, in 10% of trials, auditory stimulation led to an early termination of the sleep spindle oscillation around 150-250 msec following stimulus onset. Finally, active ON states and inactive OFF periods during slow waves in NREM sleep affected the auditory response in opposite ways, depending on stimulus intensity. CONCLUSIONS: Responses in core auditory cortex are well preserved regardless of sleep spindles recorded in that area, suggesting that thalamocortical sensory relay remains functional during sleep spindles, and that sensory disconnection in sleep is mediated by other mechanisms. PMID- 26856905 TI - The Benefits of Targeted Memory Reactivation for Consolidation in Sleep are Contingent on Memory Accuracy and Direct Cue-Memory Associations. AB - STUDY OBJECTIVES: To investigate how the effects of targeted memory reactivation (TMR) are influenced by memory accuracy prior to sleep and the presence or absence of direct cue-memory associations. METHODS: 30 participants associated each of 50 pictures with an unrelated word and then with a screen location in two separate tasks. During picture-location training, each picture was also presented with a semantically related sound. The sounds were therefore directly associated with the picture locations but indirectly associated with the words. During a subsequent nap, half of the sounds were replayed in slow wave sleep (SWS). The effect of TMR on memory for the picture locations (direct cue-memory associations) and picture-word pairs (indirect cue-memory associations) was then examined. RESULTS: TMR reduced overall memory decay for recall of picture locations. Further analyses revealed a benefit of TMR for picture locations recalled with a low degree of accuracy prior to sleep, but not those recalled with a high degree of accuracy. The benefit of TMR for low accuracy memories was predicted by time spent in SWS. There was no benefit of TMR for memory of the picture-word pairs, irrespective of memory accuracy prior to sleep. CONCLUSIONS: TMR provides the greatest benefit to memories recalled with a low degree of accuracy prior to sleep. The memory benefits of TMR may also be contingent on direct cue-memory associations. PMID- 26856906 TI - Association of Anterior Cingulate Glutathione with Sleep Apnea in Older Adults At Risk for Dementia. AB - STUDY OBJECTIVES: Sleep disordered breathing (SDB) is common in older adults and is strongly associated with cognitive decline, with increasing evidence suggesting that it may represent a risk factor for dementia. Given that SDB is characterized by intermittent episodes of hypoxemia during sleep, it is possible that cognitive impairment may relate to cerebral oxidative stress. This study aimed to examine the relationship between nocturnal markers of hypoxemia and proton magnetic resonance spectroscopy ((1)H-MRS) markers of oxidative stress within the anterior cingulate cortex (ACC) of the brain. METHODS: Twenty-four older adults (mean age = 67.9 y) at-risk for dementia were recruited from our Healthy Brain Ageing Research Clinic. At-risk was defined as participants seeking help for assessment and/or intervention for cognitive decline, including those with subjective and/or objective cognitive complaints. This could occur in the context of prior depression or risk factors (e.g., vascular) for dementia. All participants underwent psychiatric, medical and neuropsychological assessment followed by overnight polysomnography. In addition, participants underwent (1)H MRS to derive levels of ACC metabolite glutathione (GSH) reported as a ratio to creatine (GSH/Cr). RESULTS: Increased levels of GSH/Cr were associated with lower oxygen desaturation (r = -0.54, P = 0.007) and more severe apnea-hypopnea index scores during rapid eye movement sleep (r = 0.42, P = 0.050). In addition, ACC GSH/Cr correlated with poorer executive functioning (i.e., response inhibition: r = -0.49, P = 0.015; set shifting: r = -0.43, P = 0.037). CONCLUSIONS: Markers of nocturnal hypoxemia and SDB are associated with cerebral oxidative stress in older people at-risk for dementia, suggesting a potential mechanism by which SDB may contribute to brain degeneration, cognitive decline, and dementia. Further work focused on utilizing this biomarker for the early identification and treatment of this possible modifiable risk factor in older persons is now warranted. PMID- 26856908 TI - Is Restless Legs Syndrome Involved in Ambulation Related to Sleepwalking? PMID- 26856907 TI - K-Complexes: Interaction between the Central and Autonomic Nervous Systems during Sleep. AB - STUDY OBJECTIVES: To investigate the relationship between K-complexes (KCs) and cardiac functioning. METHODS: Forty healthy adolescents aged 16-22 y (19 females) participated in the study. Heart rate (HR) fluctuations associated with spontaneous and evoked KCs were investigated on two nights, one with (event related potential night) and one without auditory tones presented across the night. RESULTS: There was a clear biphasic cardiac response to evoked and spontaneous KCs, with an initial acceleration in HR followed by a deceleration (P < 0.001). HR acceleration occurred immediately to KCs in response to tones presented in the first third of the interbeat interval, but was delayed a beat when the tone occurred later in the cardiac cycle (P < 0.05). Sex differences were also evident. Pretone baseline HR was higher, and the magnitude of the HR response was blunted and delayed, in female compared to male adolescents (P < 0.001). Also, pretone baseline HR was lower when a tone elicited a KC compared to when it did not (P < 0.001), suggesting that KCs are possibly more likely to be elicited by external stimuli in states of reduced cardiac activation. CONCLUSIONS: The strict dependency observed between KCs and cardiac control indicates a potential role of KCs in modulating the cardiovascular system during sleep. Sex differences in the KC-cardiac response indicate the sensitivity of this measure in capturing sex differences in cardiac regulatory physiology. PMID- 26856910 TI - Environmental Determinants of the Distribution of Chagas Disease Vector Triatoma dimidiata in Colombia. AB - Triatoma dimidiata (Hemiptera: Reduviidae) is a secondary vector of Trypanosoma cruzi in Colombia and represents an important epidemiological risk mainly in the central and oriental regions of the country where it occupies sylvatic, peridomestic, and intradomestic ecotopes, and because of this complex distribution, its distribution and abundance could be conditioned by environmental factors. In this work, we explored the relationship between T. dimidiata distribution and environmental factors in the northwest, northeast, and central zones of Colombia and developed predictive models of infestation in the country. The associations between the presence ofT. dimidiata and environmental variables were studied using logistic regression models and ecological niche modeling for a sample of villages in Colombia. The analysis was based on the information collected in field about the presence ofT. dimidiata and the environmental data for each village extracted from remote sensing images. The presence of Triatoma dimidiata(Latreille, 1811) was found to be significantly associated with the maximum vegetation index, minimum land surface temperature (LST), and the digital elevation for the statistical model. Temperature seasonality, annual precipitation, and vegetation index were the variables that most influenced the ecological niche model ofT. dimidiata distribution. The logistic regression model showed a good fit and predicted suitable habitats in the Andean and Caribbean regions, which agrees with the known distribution of the species, but predicted suitable habitats in the Pacific and Orinoco regions proposing new areas of research. Improved models to predict suitable habitats forT. dimidiata hold promise for spatial targeting of integrated vector management. PMID- 26856911 TI - Differential Diagnosis of Japanese Encephalitis Virus Infections with the Inbios JE DetectTM and DEN DetectTM MAC-ELISA Kits. AB - Japanese encephalitis virus (JEV) is the leading cause of pediatric viral neurological disease in Asia. The JEV-specific IgM antibody-capture enzyme-linked immunosorbent assay (MAC-ELISA) in cerebrospinal fluid (CSF) and serum is the recommended method of laboratory diagnosis, but specificity of JEV MAC-ELISA can be low due to cross-reactivity. To increase the specificity of the commercially available JEDetectTM MAC-ELISA (JEDetect), a differential testing algorithm was developed in which samples tested by JEDetect with positive results were subsequently tested by the DENDetectTM MAC-ELISA (DENDetect) kit, and results of both tests were used to make the final interpretation. The testing algorithm was evaluated with a reference panel of serum and CSF samples submitted for confirmatory testing. In serum, the false Japanese encephalitis (JE) positive rate was reduced, but sequential testing in CSF resulted in reduced JE specificity, as true JEV+ CSF samples had positive results by both JEDetect and DENDetect and were classified as JE- (dengue virus [DENV]+). Differential diagnosis of JE by sequential testing with JEDetect and DENDetect increased specificity for JE in serum, but more data with CSF is needed to make a final determination on the usefulness of this testing algorithm for CSF. PMID- 26856912 TI - Rapidly Progressing Chagas Cardiomyopathy. AB - Chagas disease, caused by the parasite Trypanosoma cruzi, can cause a potentially life-threatening cardiomyopathy in approximately 10-40% of afflicted individuals. The decline in cardiac function characteristically progresses over the course of many years. We report a case of Chagas disease in which the patient experienced an atypical rapid deterioration to severe cardiomyopathy over the course of 16 months. This case argues the need for increased routine surveillance for patients with confirmed T. cruzi infection, who are determined to be at high-risk for worsening cardiomyopathy. PMID- 26856909 TI - A Randomized Comparison of Chloroquine Versus Dihydroartemisinin-Piperaquine for the Treatment of Plasmodium vivax Infection in Vietnam. AB - A total of 128 Vietnamese patients with symptomatic Plasmodium vivax mono infections were enrolled in a prospective, open-label, randomized trial to receive either chloroquine or dihydroartemisinin-piperaquine (DHA-PPQ). The proportions of patients with adequate clinical and parasitological responses were 47% in the chloroquine arm (31 of 65 patients) and 66% in the DHA-PPQ arm (42 of 63 patients) in the Kaplan-Meier intention-to-treat analysis (absolute difference 19%, 95% confidence interval = 0-37%), thus establishing non-inferiority of DHA PPQ. Fever clearance time (median 24 versus 12 hours,P= 0.02), parasite clearance time (median 36 versus 18 hours,P< 0.001), and parasite clearance half-life (mean 3.98 versus 1.80 hours,P< 0.001) were all significantly shorter in the DHA-PPQ arm. All cases of recurrent parasitemia in the chloroquine arm occurred from day 33 onward, with corresponding whole blood chloroquine concentration lower than 100 ng/mL in all patients. Chloroquine thus remains efficacious for the treatment of P. vivax malaria in southern Vietnam, but DHA-PPQ provides more rapid symptomatic and parasitological recovery. PMID- 26856913 TI - Limited Degradation of the Plasmodium falciparum Gametocyte Marker pfs25 mRNA Exposed to Tropical Temperatures: Considerations for Malaria Transmission Field Studies. AB - An important aspect of many malaria molecular epidemiology and transmission studies is RNA-based detection of gametocytes. Ensuring RNA stability represents a challenge in tropical, resource-limited environments, as RNA may quickly degrade when samples are not preserved under adequate conditions. This study investigated the degradation of pfs25 messenger RNA (mRNA), the most widely used Plasmodium falciparum gametocyte marker, in whole blood spiked with cultured P. falciparum gametocytes, exposed to different temperatures for up to 48 hours, and collected with different anticoagulants. The levels of pfs25 mRNA were similar between samples stored at 4 degrees C and 30 degrees C for up to 48 hours before stabilization with RNAprotect (Qiagen, Hilden, Germany). We observed that pfs25 mRNA in heparin-collected blood degraded less than that in ethylenediaminetetraacetic acid (EDTA)-collected blood over the 48-hour period. For field studies aiming for P. falciparum gametocyte detection, immediate stabilization of blood samples is not necessary, as the pfs25 transcript is relatively stable, more so in heparin than EDTA collection tubes. PMID- 26856915 TI - Modeling Key Malaria Drugs' Impact on Global Health: A Reason to Invest in the Global Health Impact Index. AB - Millions of people cannot access good quality essential medicines they need for some of the world's worst diseases like malaria. The World Health Organization estimates that, in 2013, 198 million people became sick with malaria and 584,000 people died of the disease, while the Institute for Health Metrics Evaluation estimates that there were 164,929,872 cases of malaria in 2013 and 854,568 deaths in 2013. There are many attempts to model different aspects of the global burden of tropical diseases like malaria, but it is also important to measure success in averting malaria-related death and disability. This perspective proposes investing in a systematic effort to measure the benefits of health interventions for malaria along the lines of a model embodied in the Global Health Impact Index (global-health-impact.org). PMID- 26856914 TI - Ecological Niche Modeling for the Prediction of the Geographic Distribution of Cutaneous Leishmaniasis in Tunisia. AB - Cutaneous leishmaniasis is a very complex disease involving multiple factors that limit its emergence and spatial distribution. Prediction of cutaneous leishmaniasis epidemics in Tunisia remains difficult because most of the epidemiological tools used so far are descriptive in nature and mainly focus on a time dimension. The purpose of this work is to predict the potential geographic distribution of Phlebotomus papatasi and zoonotic cutaneous leishmaniasis caused by Leishmania major in Tunisia using Grinnellian ecological niche modeling. We attempted to assess the importance of environmental factors influencing the potential distribution of P. papatasi and cutaneous leishmaniasis caused by L. major. Vectors were trapped in central Tunisia during the transmission season using CDC light traps (John W. Hock Co., Gainesville, FL). A global positioning system was used to record the geographical coordinates of vector occurrence points and households tested positive for cutaneous leishmaniasis caused by L. major. Nine environmental layers were used as predictor variables to model the P. papatasi geographical distribution and five variables were used to model the L. major potential distribution. Ecological niche modeling was used to relate known species' occurrence points to values of environmental factors for these same points to predict the presence of the species in unsampled regions based on the value of the predictor variables. Rainfall and temperature contributed the most as predictors for sand flies and human case distributions. Ecological niche modeling anticipated the current distribution of P. papatasi with the highest suitability for species occurrence in the central and southeastern part of Tunisian. Furthermore, our study demonstrated that governorates of Gafsa, Sidi Bouzid, and Kairouan are at highest epidemic risk. PMID- 26856917 TI - Phylogenetic Analysis of Chikungunya Virus Strains Circulating in the Western Hemisphere. AB - In December 2013, chikungunya virus (CHIKV) was isolated for the first time in the Western Hemisphere (WH) during an epidemic on the island of St. Martin. Subsequently, the virus has spread to 42 countries or territories in the Caribbean, Central, South, and North America. In this study, we have determined the full genomic sequences of 29 temporally and geographically diverse CHIKV strains from 16 countries of the WH. Phylogenetic analyses revealed minimal evolution among compared emergent CHIKV strains of the New World. PMID- 26856918 TI - Transcript Abundance of Putative Lipid Phosphate Phosphatases During Development of Trypanosoma brucei in the Tsetse Fly. AB - African trypanosomes (Trypanosoma brucei spp.) cause devastating diseases in sub Saharan Africa. Trypanosomes differentiate repeatedly during development in tsetse flies before gaining mammalian infectivity in fly salivary glands. Lipid phosphate phosphatases (LPPs) are involved in diverse biological processes, such as cell differentiation and cell migration. Gene sequences encoding two putative T. brucei LPP proteins were used to search the T. brucei genome, revealing two additional putative family members. Putative structural features and transcript abundance during parasite development in tsetse fly were characterized. Three of the four LPP proteins are predicted to have six transmembrane domains, while the fourth shows only one. Semiquantitative gene expression revealed differential regulation of LPPs during parasite development. Transcript abundance for three of the four putative LPP genes was elevated in parasites infecting salivary glands, but not mammalian-infective metacyclic cells in fly saliva, indicating a potential role of this family in parasite establishment in tsetse salivary glands. PMID- 26856916 TI - The Effect of Temperature on Wolbachia-Mediated Dengue Virus Blocking in Aedes aegypti. AB - Dengue fever, caused by dengue virus (DENV), is endemic in more than 100 countries. The lack of effective treatment of patients and the suboptimal efficacies of the tetravalent vaccine in trials highlight the urgent need to develop alternative strategies to lessen the burden of dengue fever.Wolbachia pipientis, an obligate intracellular bacterium, is being developed as a biocontrol strategy against dengue because it limits the replication of the DENV in the mosquito vector,Aedes aegypti However, several recent studies have demonstrated the sensitivity of pathogens, vectors, and their symbionts to temperature. To understand how the tripartite interactions between the mosquito, DENV, and Wolbachia may change under different temperature regimes, we assessed the vector competence and transmission potential of DENV-infected mosquitoes reared at a common laboratory setting of a constant 25 degrees C and at two diurnal temperature settings with mean of 25 degrees C and 28 degrees C and a fluctuating range of 8 degrees C (+/-4 degrees C). Temperature significantly affected DENV infection rate in the mosquitoes. Furthermore, temperature significantly influenced the proportion of mosquitoes that achieved transmission potential as measured by the presence of virus in the saliva. Regardless of the temperature regimes,Wolbachia significantly and efficiently reduced the proportion of mosquitoes achieving infection and transmission potential across all the temperature regimes studied. This work reinforces the robustness of the Wolbachia biocontrol strategy to field conditions in Cairns, Australia, and suggests that similar studies are required for local mosquito genotypes and field relevant temperatures for emerging field release sites globally. PMID- 26856919 TI - Population Density, Poor Sanitation, and Enteric Infections in Nueva Santa Rosa, Guatemala. AB - Poor sanitation could pose greater risk for enteric pathogen transmission at higher human population densities because of greater potential for pathogens to infect new hosts through environmentally mediated and person-to-person transmission. We hypothesized that incidence and prevalence of diarrhea, enteric protozoans, and soil-transmitted helminth infections would be higher in high population-density areas compared with low-population-density areas, and that poor sanitation would pose greater risk for these enteric infections at high density compared with low density. We tested our hypotheses using 6 years of clinic-based diarrhea surveillance (2007-2013) including 4,360 geolocated diarrhea cases tested for 13 pathogens and a 2010 cross-sectional survey that measured environmental exposures from 204 households (920 people) and tested 701 stool specimens for enteric parasites. We found that population density was not a key determinant of enteric infection nor a strong effect modifier of risk posed by poor household sanitation in this setting. PMID- 26856921 TI - Antischistosomal activity of N,N'-arylurea analogs against Schistosoma japonicum. AB - Although the antischistosomal activities of N,N'-arylurea analogs were reported, systematic structure-activity relationships have not been conducted. In this Letter, we reported the design, synthesis and evaluation of 45 N,N'-arylurea analogs. Among these prepared compounds, 13 compounds were urea linker modified and 32 were N,N'-arylurea derivatives. The activity evaluation revealed 12 analogs exhibited IC50 values lower than 22.6MUM, and 7 of them had IC50 less than 10MUM against the juvenile Schistosoma japonicum in vitro. Their worm killing potency was even higher against adult worm. Unfortunately, low to moderate worm burden reduction of 0-33.4% was recorded after administration of a single oral dose of 200mg/kg or 400mg/kg to mice harboring S. japonicum. PMID- 26856920 TI - Synthesis and radiolabeling of (64)Cu-labeled 2-nitroimidazole derivative (64)Cu BMS2P2 for hypoxia imaging. AB - The objective of this study was to develop a positron emission tomography (PET) probe with hypoxia targeting specificity and a relatively long half-life. The synthesis, (64)Cu-labeling in vitro and in vivo study of the novel 2 nitroimidazole complex (64)Cu-BMS2P2 is presented in this study. The hypoxia targeting capacity of (64)Cu-BMS2P2 in vitro was evaluated and compared with the (64)Cu-BMS181321, and confirmed by PET imaging in vivo and immunohistochemistry for carbonic anhydrase 9 (CA9) in a tumor mouse model. These results suggest that (64)Cu-BMS2P2 is a promising candidate for PET hypoxia imaging and worthy of further investigations in dynamic hypoxia imaging. PMID- 26856922 TI - Synthesis of carbon-11-labeled imidazopyridine- and purine-thioacetamide derivatives as new potential PET tracers for imaging of nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). AB - The target tracer carbon-11-labeled imidazopyridine- and purine-thioacetamide derivatives, N-(3-[(11)C]methoxy-4-methoxyphenyl)-2-((5-methoxy-3H-imidazo[4,5 b]pyridin-2-yl)thio)acetamide (3-[(11)C]4a) and N-(4-[(11)C]methoxy-3 methoxyphenyl)-2-((5-methoxy-3H-imidazo[4,5-b]pyridin-2-yl)thio)acetamide (4 [(11)C]4a); 2-((6-amino-9H-purin-8-yl)thio)-N-(3-[(11)C]methoxy-4 methoxyphenyl)acetamide (3-[(11)C]8a) and 2-((6-amino-9H-purin-8-yl)thio)-N-(4 [(11)C]methoxy-3-methoxyphenyl)acetamide (4-[(11)C]8a), were prepared by O [(11)C]methylation of their corresponding precursors with [(11)C]CH3OTf under basic condition (2N NaOH) and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields based on [(11)C]CO2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 185-555GBq/MUmol. PMID- 26856923 TI - Carbonic anhydrase activators: Activation of the beta-carbonic anhydrase from Malassezia globosa with amines and amino acids. AB - The beta-carbonic anhydrase (CA, EC 4.2.1.1) from the dandruff producing fungus Malassezia globosa, MgCA, was investigated for its activation with amines and amino acids. MgCA was weakly activated by amino acids such as L-/D-His, L-Phe, D DOPA, D-Trp, L-/D-Tyr and by the amine serotonin (KAs of 12.5-29.3MUM) but more effectively activated by d-Phe, l-DOPA, l-Trp, histamine, dopamine, pyridyl alkylamines, and 4-(2-aminoethyl)-morpholine, with KAs of 5.82-10.9MUM. The best activators were l-adrenaline and 1-(2-aminoethyl)piperazine, with activation constants of 0.72-0.81MUM. This study may help a better understanding of the activation mechanisms of beta-CAs from pathogenic fungi as well as the design of tighter binding ligands for this enzyme which is a drug target for novel types of anti-dandruff agents. PMID- 26856924 TI - Revised structure of trans-resveratrol: Implications for its proposed antioxidant mechanism. AB - The crystal structure of trans-resveratrol has been redetermined by X-ray diffraction. The newly refined structure demonstrates that the previously reported, dynamically disordered hydrogen-bonding network is rather the superposition of two crystallographically independent molecules of trans resveratrol. This latter arrangement possesses a well-defined hydrogen-bonding network in a unit cell of double the previously reported volume. While not meant as a criticism of the proposed antioxidant mechanism itself, the present studies clearly show that the X-ray diffraction data should no longer be used for its additional support. PMID- 26856925 TI - Hereditary multiple exostoses: A case-report. PMID- 26856926 TI - Efficacy and Safety of DP-R202 in Patients with Chronic Artery Occlusive Disease: Multicenter Randomized Double-blind Active-controlled Parallel Group Phase III Clinical Study. AB - PURPOSE: Sarpogrelate hydrochloride, a selective 5-hydroxytryptamine 2A antagonist, is a widely used antiplatelet agent for the treatment of peripheral arterial disease (PAD). DP-R202 is a new sarpogrelate hydrochloride product with an improved dosage regimen compared with the agent in current use. The aim of this study was to compare the efficacy and safety profile of DP-R202 and Anplag(*) Tab in patients with PAD. METHODS: This study was a 12-week, multicenter, randomized, double-blinded, active-controlled, parallel group comparative Phase III clinical trial. One hundred fifty-one volunteer patients with PAD were randomized to receive DP-R202 300 mg once daily or Anplag Table 100 mg TID for 12 weeks. The primary end point was a change in patient assessment of lower leg pain intensity with the use of a visual analog scale (VAS) after 12 weeks of treatment. Results after 4, 8, and 12 weeks of treatment were compared with baseline and between treatment groups, and all patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. FINDINGS: Two hundred thirty-one patients from 25 medical centers were assessed, and 151 were enrolled and randomly assigned to 1 of 2 treatment groups. Seventy-five patients received DP-R202 300 mg once daily and 76 patients received Anplag Table 100 mg TID for 12 weeks. Analysis of the change in lower leg pain intensity as determined by VAS score between baseline and week 12 (mean [SD], 20.72 [20.06] mm vs 15.55 [21.44] mm) suggested that DP-R202 was not inferior to Anplag Tab, and no significant differences were found in the secondary end points. No significant between-group differences were observed in the prevalence of drug-related clinical- or laboratory-determined AEs. For tolerability, no specific issue was found during the treatment period. IMPLICATION: The results of this study suggest that DP-R202 was not inferior to Anplag Tab for efficacy in patients with PAD and indicated a good safety profile. PMID- 26856927 TI - Health Care Resource Utilization, Costs, and Persistence in Patients Newly Diagnosed as Having Nonvalvular Atrial Fibrillation and Newly Treated With Dabigatran versus Warfarin in the United States. AB - PURPOSE: This study compared health care resource utilization (HCRU), costs, and persistence among patients newly diagnosed as having nonvalvular atrial fibrillation (NVAF) and newly treated with dabigatran versus warfarin. METHODS: This retrospective claims-based study used data from a large US managed care organization. The earliest claim for dabigatran or warfarin during October 1, 2010 through October 31, 2011 was the index date, with cohort assignment based on index medication. Evidence of newly diagnosed NVAF within 30 days before the index date and no claims for oral anticoagulants during the 12-month preindex period were required. Cohorts were matched using propensity scores. Per-patient per-month HCRU, costs, and persistence were calculated during the variable follow up period of up to 12 months after the index date. Descriptive and multivariable analyses were used to examine differences in outcomes. FINDINGS: After matching, 869 patients per cohort were identified (mean age, 67.8 years; 40.4% female). Compared with warfarin, dabigatran had fewer per-patient-per-month emergency department (0.10 vs 0.13, P = 0.010), office (1.98 vs 2.96, P < 0.001), and outpatient (1.05 vs 1.48, P < 0.001) visits. Despite higher mean pharmacy costs for dabigatran (P < 0.001), mean total health care (P = 0.309) and medical costs (P = 0.568) were similar to warfarin. Persistence was higher with dabigatran versus warfarin (median, 204 vs 161 days; mean, 213.7 vs 195.5 days, P = 0.001). IMPLICATIONS: Among patients newly diagnosed as having NVAF, those newly treated with dabigatran had lower HCRU, higher persistence, and similar total health care costs compared with those treated with warfarin. PMID- 26856928 TI - Immune-reconstitution Inflammatory Syndrome in Multiple Sclerosis Patients Treated With Natalizumab: A Series of 4 Cases. AB - PURPOSE: Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Progressive multifocal leukoencephalopathy (PML) is a rare complication of NTZ treatment. In patients developing PML, NTZ cessation causes a reconstruction of cellular immunity, a rapid transition of cells through the blood-brain barrier, and significant inflammation in the central nervous system, leading to immune-reconstitution inflammatory syndrome (IRIS), with potentially poor outcomes. The occurrence of this syndrome is accelerated by plasmapheresis, the standard treatment for NTZ-PML, due to enhanced clearance of NTZ and thus rapid reconstitution of cellular immunity. IRIS can also occur after cessation of NTZ in the absence of PML. METHODS: We describe 4 patients who developed IRIS after NTZ cessation. FINDINGS: For the first patient, treatment was switched to fingolimod to avoid risk of developing PML. Despite plasmapheresis, corticosteroids, and other therapies, the outcome in this patient was fatal. For the 3 other patients, PML was detected early on magnetic resonance imaging, and IRIS after NTZ cessation was managed with a favorable outcome; 1 of these patients was managed without plasmapheresis or corticosteroid treatment. IMPLICATIONS: These cases demonstrate the need to consider and manage therapeutic strategies relative to the individual patient's risk for PML or IRIS. NTZ cessation to avoid PML risk can lead to severe IRIS without PML. On the other hand, if PML develops and is detected early, plasmapheresis may not be considered necessary and IRIS may be limited, with a favorable outcome. These 2 scenarios should be considered when managing NTZ MS patients. PMID- 26856929 TI - The Cost-effectiveness of Pixantrone for Third/Fourth-line Treatment of Aggressive Non-Hodgkin's Lymphoma. AB - PURPOSE: Aggressive non-Hodgkin's lymphoma (aNHL) is associated with poor long term survival after relapse, and treatment is limited by a lack of consensus regarding standard of care. Pixantrone was studied in a randomized trial in patients with relapsed or refractory aNHL who had failed >= 2 lines of therapy, demonstrating a significant improvement in complete or unconfirmed complete response and progression-free survival (PFS) compared with investigators' choice of single-agent therapy. The objective of this study was to assess the health economic implications of pixantrone versus current clinical practice (CCP) in the United Kingdom for patients with multiply relapsed or refractory aNHL receiving their third or fourth line of treatment. METHODS: A semi-Markov partition model based on overall survival and PFS was developed to evaluate the lifetime clinical and economic impact of treatment of multiply relapsed or refractory aNHL with pixantrone versus CCP. The empirical overall survival and PFS data from the PIX301 trial were extrapolated to a lifetime horizon. Resource use was elicited from clinical experts, and unit costs and utilities were obtained from published sources. The analysis was conducted from the perspective of the United Kingdom's National Health Service and personal social services. Outcomes evaluated were total costs, life-years, quality-adjusted life-years (QALYs), and cost per QALY gained. Deterministic and probabilistic sensitivity analyses were conducted to assess uncertainty around the results. FINDINGS: Pixantrone was estimated to increase life expectancy by a mean of 10.8 months per patient compared with CCP and a mean gain of 0.56 discounted QALYs. The increased health gains were associated with an increase in discounted costs of approximately L18,494 per patient. The incremental cost-effectiveness ratio of pixantrone versus CCP was L33,272 per QALY gained. Sensitivity and scenario analyses suggest that the incremental cost-effectiveness ratio was sensitive to uncertainty in the PFS and overall survival estimates and the utility values associated with each health state. IMPLICATIONS: Pixantrone may be considered both clinically effective and cost-effective for patients with multiply relapsed or refractory aNHL who currently have a high level of unmet need. PMID- 26856930 TI - A new tritiated water measurement method with plastic scintillator pellets. AB - A new tritiated water measurement method with plastic scintillator pellets (PS pellets) by using a conventional liquid scintillation counter was developed. The PS-pellets used were 3 mm in both diameter and length. A low potassium glass vial was filled full with the pellets, and tritiated water was applied to the vial from 5 to 100 MUl. Then, the sample solution was scattered in the interstices of the pellets in a vial. This method needs no liquid scintillator, so no liquid organic waste fluid is generated. The counting efficiency with the pellets was approximately 48 % when a 5 MUl solution was used, which was higher than that of conventional measurement using liquid scintillator. The relationship between count rate and activity showed good linearity. The pellets were able to be used repeatedly, so few solid wastes are generated with this method. The PS-pellets are useful for tritiated water measurement; however, it is necessary to develop a new device which can be applied to a larger volume and measure low level concentration like an environmental application. PMID- 26856931 TI - Infertility and uterine fibroids. AB - Uterine fibroids are the most common tumors in women and their prevalence is higher in patients with infertility. At present, they are classified according to their anatomical location, as no classification system includes additional parameters such as their size or number. There is a general agreement that submucosal fibroids negatively affect fertility, when compared to women without fibroids. Intramural fibroids above a certain size (>4 cm), even without cavity distortion, may also negatively influence fertility. However, the presence of subserosal myomas has little or no effect on fertility. Many possible theories have been proposed to explain how fibroids impair fertility: mechanisms involving alteration of local anatomical location, others involving functional changes of the myometrium and endometrium, and finally endocrine and paracrine molecular mechanisms. Nevertheless, any of the above mentioned mechanisms can cause reduced reproductive potential, thereby leading to impaired gamete transport, reduced ability for embryo implantation, and creation of a hostile environment. The published experience defines the best practice strategy, as not many large, well designed, and properly powered studies are available. Myomectomy appears to have an effect in fertility improvement in certain cases. Excision of submucosal myomas seems to restore fertility with pregnancy rates after surgery similar to normal controls. Removal of intramural myomas affecting pregnancy outcome seems to be associated with higher pregnancy rates when compared to non-operated controls, although evidence is still nomicront sufficient. Treatment of subserosal myomas of reasonable size is not necessary for fertility reasons. The results of endoscopic and open myomectomy are similar; thus, endoscopic treatment is the recommended approach due to its advantages in patient's postoperative course. PMID- 26856932 TI - Rational Hydrogenation for Enhanced Mobility and High Reliability on ZnO-based Thin Film Transistors: From Simulation to Experiment. AB - Hydrogenation is one of the effective methods for improving the performance of ZnO thin film transistors (TFTs), which originate from the fact that hydrogen (H) acts as a defect passivator and a shallow n-type dopant in ZnO materials. However, passivation accompanied by an excessive H doping of the channel region of a ZnO TFT is undesirable because high carrier density leads to negative threshold voltages. Herein, we report that Mg/H codoping could overcome the trade off between performance and reliability in the ZnO TFTs. The theoretical calculation suggests that the incorporation of Mg in hydrogenated ZnO decrease the formation energy of interstitial H and increase formation energy of O-vacancy (VO). The experimental results demonstrate that the existence of the diluted Mg in hydrogenated ZnO TFTs could be sufficient to boost up mobility from 10 to 32.2 cm(2)/(V s) at a low carrier density (~2.0 * 10(18) cm(-3)), which can be attributed to the decreased electron effective mass by surface band bending. The all results verified that the Mg/H codoping can significantly passivate the VO to improve device reliability and enhance mobility. Thus, this finding clearly points the way to realize high-performance metal oxide TFTs for low-cost, large volume, flexible electronics. PMID- 26856935 TI - The influence of clinical information in electrocardiogram interpretation. PMID- 26856936 TI - Specific clinical phenotypes in relapsing multiple sclerosis: The impact of relapses on long-term outcomes. AB - OBJECTIVE: The impact of relapses on the disease course of relapsing MS remains to be determined. This study aims to identify and characterize clinical phenotypes of relapse onset MS in a longitudinally studied cohort. METHODS: We recorded the clinical course of MS during the first decade of disease, using five year epochs. Patients were stratified as: no worsening due to relapse or secondary progression (type A), relapse with worsening seen without secondary progression (type B), secondary progression with no worsening due to relapse (type C), worsening due to relapses mixed with secondary progression (type D). RESULTS: Of 176 patients followed from diagnosis for 12.62 +/- 4.18 years, 93.2% (164/176) had increased disability in their first 5-year epoch of MS and 52.2% (72/138) in the next. The phenotypes significantly differed by EDSS change during each epoch (p<0.001), final confirmed MSSS (p <= 0.002) and relapse rate (p<0.001). Type D fared worse than others by change in EDSS and MSSS. CONCLUSION: We identified multiple specific phenotypes of MS and temporal shifts between phenotypes according to relapse type and progression. PMID- 26856937 TI - Identifying clues to molecular etiology of multiple sclerosis in South Indian patients. AB - BACKGROUND: Environmental risk factors have a dominant role in the pathogenesis of multiple sclerosis (MS). Unhealthy lifestyle can predispose people to autoimmune diseases. MS was a rare disease in Kerala, but now, we notice frequent cases of MS at the city neurology clinic. Changing lifestyle and associated changes in the level of proinflammatory biomolecules like: leptin, soluble leptin receptor (SLR) and free fatty acids (FA) could be contributing to rise in MS incidence. OBJECTIVE: To identify variations in the levels of bio-molecules: leptin, SLR and FA, between MS patients and matched healthy control. METHOD: Leptin and SLR levels in the blood serum, were estimated using ELISA, while total FA levels, were estimated using an enzyme based calorimetric assay. RESULT: Mean serum FA levels in MS patients (31.39 +/- 4.83 nmole/100 MUl) were 2.7 fold higher than controls (11.54 +/- 2.66 nmoles/100 MUl) at more than 99% CI. The differences in mean leptin and SLR levels were not statistically significant. CONCLUSION: MS patients had high level of total FA in their blood. High FA in blood may have a role in MS pathogenesis. More in-depth study is required to understand the precise mechanism by which FA rise in MS blood sample can contribute to pathogenesis. PMID- 26856934 TI - Integrative Genomic Analyses Yield Cell-Cycle Regulatory Programs with Prognostic Value. AB - Liposarcoma is the second most common form of sarcoma, which has been categorized into four molecular subtypes, which are associated with differential prognosis of patients. However, the transcriptional regulatory programs associated with distinct histologic and molecular subtypes of liposarcoma have not been investigated. This study uses integrative analyses to systematically define the transcriptional regulatory programs associated with liposarcoma. Likewise, computational methods are used to identify regulatory programs associated with different liposarcoma subtypes, as well as programs that are predictive of prognosis. Further analysis of curated gene sets was used to identify prognostic gene signatures. The integration of data from a variety of sources, including gene expression profiles, transcription factor-binding data from ChIP-Seq experiments, curated gene sets, and clinical information of patients, indicated discrete regulatory programs (e.g., controlled by E2F1 and E2F4), with significantly different regulatory activity in one or multiple subtypes of liposarcoma with respect to normal adipose tissue. These programs were also shown to be prognostic, wherein liposarcoma patients with higher E2F4 or E2F1 activity associated with unfavorable prognosis. A total of 259 gene sets were significantly associated with patient survival in liposarcoma, among which > 50% are involved in cell cycle and proliferation. IMPLICATIONS: These integrative analyses provide a general framework that can be applied to investigate the mechanism and predict prognosis of different cancer types. PMID- 26856933 TI - Non-alcoholic fatty liver disease and diabetes. AB - Non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2DM) are common conditions that regularly co-exist and can act synergistically to drive adverse outcomes. The presence of both NAFLD and T2DM increases the likelihood of the development of complications of diabetes (including both macro- and micro- vascular complications) as well as augmenting the risk of more severe NAFLD, including cirrhosis, hepatocellular carcinoma and death. The mainstay of NAFLD management is currently to reduce modifiable metabolic risk. Achieving good glycaemic control and optimising weight loss are pivotal to restricting disease progression. Once cirrhosis has developed, it is necessary to screen for complications and minimise the risk of hepatic decompensation. Therapeutic disease modifying options for patients with NAFLD are currently limited. When diabetes and NAFLD co-exist, there are published data that can help inform the clinician as to the most appropriate oral hypoglycaemic agent or injectable therapy that may improve NAFLD, however most of these data are drawn from observations in retrospective series and there is a paucity of well-designed randomised double blind placebo controlled studies with gold-standard end-points. Furthermore, given the heterogeneity of inclusion criteria and primary outcomes, as well as duration of follow-up, it is difficult to draw robust conclusions that are applicable across the entire spectrum of NAFLD and diabetes. In this review, we have summarised and critically evaluated the available data, with the aim of helping to inform the reader as to the most pertinent issues when managing patients with co-existent NAFLD and T2DM. PMID- 26856939 TI - Multiple sclerosis relapse mimicking a transient ischemic attack. PMID- 26856938 TI - Systematic review and meta-analysis of interventions for depression and anxiety in persons with multiple sclerosis. AB - BACKGROUND: Depression and anxiety are common in persons with multiple sclerosis (MS), and adversely affect fatigue, medication adherence, and quality of life. Though effective treatments for depression and anxiety exist in the general population, their applicability in the MS population has not been definitively established. OBJECTIVE: To determine the overall effect of psychological and pharmacological treatments for depression or anxiety in persons with MS. METHODS: We searched the Medline, EMBASE, PsycINFO, PsycARTICLES Full Text, Cochrane Central Register of Controlled Trials, CINAHL, Web of Science, and Scopus databases using systematic review methodology from database inception until March 25, 2015. Two independent reviewers screened abstracts, extracted data, and assessed risk of bias and strength of evidence. We included controlled clinical trials reporting on the effect of pharmacological or psychological interventions for depression or anxiety in a sample of persons with MS. We calculated standardized mean differences (SMD) and pooled using random effects meta analysis. RESULTS: Of 1753 abstracts screened, 21 articles reporting on 13 unique clinical trials met the inclusion criteria. Depression severity improved in nine psychological trials of depression treatment (N=307; SMD: -0.45 (95%CI: -0.74, 0.16)). The severity of depression also improved in three pharmacological trials of depression treatment (SMD: -0.63 (N=165; 95%CI: -1.07, -0.20)). For anxiety, only a single trial examined psychological therapy for injection phobia and reported no statistically significant improvement. CONCLUSION: Pharmacological and psychological treatments for depression were effective in reducing depressive symptoms in MS. The data are insufficient to determine the effectiveness of treatments for anxiety. PMID- 26856940 TI - Longitudinal associations between brain structural changes and fatigue in early MS. AB - BACKGROUND: Fatigue is a common and disabling symptom of multiple sclerosis (MS) patients. Structural changes in several brain areas have been reported to correlate with fatigue in MS patients but none consistently. OBJECTIVE: To study the association between global and regional measures of brain atrophy and fatigue in patients with early relapsing MS. METHODS: Clinically isolated syndrome and relapsing MS patients within 12 months of clinical onset were enrolled in a neuroprotection trial of riluzole versus placebo with up to 36 months of follow up. MRI metrics included brain volumes measured by SIENAX normalized measurements [normalized brain parenchymal volume (nBPV), normalized normal-appearing white and gray matter volume (nNAWMV and nGMV)] and T2 lesion volume (T2LV). Cortical thickness, thalamic volume and cerebellar cortical volume were measured using Freesurfer's longitudinal pipeline (v5.3) and a lesion inpainting approach. Fatigue was evaluated using the Modified Fatigue Impact Scale (MFIS). Mixed model regression measured time trends and associations between imaging and fatigue severity, adjusting for age and sex. RESULTS: Forty-three patients (mean age 36 years; 31 females) were enrolled within 7.5 +/- 4.9 months of symptom onset. Baseline and change over baseline in lesion volumes, grey matter, white matter, basal ganglia and total parenchymal volumes were not associated with change in MFIS score over time. Lower thalamic volume at baseline predicted increasing physical subscale of MFIS score during the study (p=0.017). There was a trend toward baseline thalamic volume and cerebellar cortical volume predicting subsequent change in total MFIS score (p=0.055 and 0.082 respectively). On-study change in thalamic or cerebellar cortical volume was not associated with on-study change in MFIS score. CONCLUSION: Global measures of tissue loss are not strongly associated with fatigue in patients with early MS. However, thalamic and cerebellar cortical atrophy may be predictive of subsequent changes in fatigue in these patients. PMID- 26856941 TI - Spasticity in multiple sclerosis: Associations with impairments and overall quality of life. AB - OBJECTIVES: DESIGN: Cross-sectional survey. SETTING: A convenience sample of people with MS routinely attending an appointment with their local MS service. PARTICIPANTS: 701 patients with clinically definite MS. MAIN OUTCOME MEASURES: Demographic details were obtained and patients completed a battery of measures including spasticity (Multiple Sclerosis Spasticity Scale - 88), fatigue (Neurological Fatigue Index - MS), urinary dysfunction (Qualiveen-SF), pain (Neuropathic Pain Scale), mood disorder (Hospital Anxiety and Depression Scale), disability (World Health Organisation Disability Assessment Schedule) and QOL (Leeds Multiple Sclerosis QOL Scale). RESULTS: 85.7% of patients reported spasticity. Patients with higher levels of spasticity were more likely to be disabled, suffer from depression and anxiety, have higher levels of fatigue and report more pain and bladder problems (p<0.01). Spasticity remained as a significant direct effect upon QOL in a multivariate model adjusted for other impairments, activity limitation and depression. CONCLUSIONS: There is a strong association between spasticity and fatigue, depression, anxiety, pain and bladder problems. The retention of a significant direct relationship with QOL in a multivariate model emphasises its influence upon the everyday lives of people with MS. PMID- 26856942 TI - The management and outcomes of fingolimod first dose cardiac monitoring in UK patients with relapsing-remitting multiple sclerosis. AB - BACKGROUND: Patients initiated on Gilenya (fingolimod) require cardiovascular monitoring for 6h after the first dose. Novartis has engaged an independent provider (Regent's Park Heart Clinics [RPHC]) to provide a first dose observation (FDO) service to UK neurologists. OBJECTIVES: To describe routinely-documented clinical observations (heart rate [HR], blood pressure [BP], cardiac rhythm [CR]) and outcomes from the RPHC fingolimod FDO service. METHODS: Pseudonymised data (clinical observations pre-dose and for 6h after the first dose and any requirement for extended monitoring) were collected retrospectively from RPHC records for the first 850 RPHC FDO episodes (undertaken Jul-2012 to Jan-2015). All episodes involved patients with relapsing-remitting MS who were initiated on fingolimod in routine National Health Service (NHS) clinical practice. RESULTS: In 78% of FDO episodes the patient was female. Mean age at date of episode was 40.1 years. Mean HR was 72.7 bpm (beats per minute) pre-dose, 64.3 bpm at 5h (the lowest recorded HR) and 66.1 bpm at 6h post-dose. New-onset heart block was observed in 2% of episodes (1.5% first-degree; 0.5% second-degree). The patient was discharged at 6 hours post-dose in 97% of episodes and required extended monitoring in 3%. In 5 episodes overnight monitoring was required. There were no episodes in which the patient required pharmacological intervention or temporary cardiac pacing. CONCLUSIONS: In this real-world UK population fingolimod initiation was predominantly uneventful; clinical observations were similar to previous clinical trials. PMID- 26856943 TI - Longitudinal associations between MRI and cognitive changes in very early MS. AB - OBJECTIVES: Cognitive dysfunction in multiple sclerosis (MS) has been primarily examined in patients with advanced disease. Our objective was to study the longitudinal associations between brain magnetic resonance imaging (MRI) metrics and neuropsychological outcomes in patients with early MS. METHODS: Relapsing MS patients within 12 months of onset were enrolled in a neuroprotection trial of riluzole versus placebo with up to 36 months of follow-up. MRI metrics included percent brain volume changes measured by SIENAX normalized measurements [normalized brain parenchymal volume (nBPV), normalized normal-appearing white and gray matter volume (nNAWMV and nGMV)] and T2 lesion volume (T2LV). A neuropsychological battery was performed annually. Mixed model regression measured time trends and associations between imaging and neuropsychological outcomes, adjusting for sex, age and education level. RESULTS: Forty-three patients (mean age 36 years; 31 females) were enrolled within 7.5 +/- 4.9 months of disease onset. 11.6% of patients with baseline cognitive assessment met conservative criteria for cognitive impairment. Compared to placebo, riluzole had no significant effect on neuropsychological performance; thus, both groups were combined for the association analyses. Baseline T2LV predicted subsequent changes in PASAT (p=0.006) and SDMT (p=0.002) scores. Longitudinal changes of T2LV were associated with changes in CVLT-II (p<0.001). CONCLUSION: These findings suggest that cognitive impairment is relatively common in patients with very early MS. Baseline and longitudinal changes in the lesion load may be associated with some of the most frequently identified changes in cognitive function in MS. PMID- 26856945 TI - Ganglion cell analysis in acute optic neuritis. AB - BACKGROUND: Optic neuritis has a diagnostic and prognostic significance in predicting the development of multiple sclerosis. Optical coherence tomography is being increasingly used to detect and monitor axonal damage in MS by measuring the retinal nerve fiber layer (RNFL). However, RNFL can be affected by edema and inflammation and obscure early axonal damage. OBJECTIVE: To study the pattern of change in the ganglion cell and inner plexiform layer compared to retinal nerve fibber layer in acute optic neuritis using spectral domain OCT. METHODS: Ten patients with acute optic neuritis were followed prospectively for 6 months with spectral domain optical coherence tomography. A group of 40 of eyes of 20 healthy controls was used for baseline comparison. RESULTS: The ganglion cell and inner plexiform layer (GCIPL) was significantly lower (thinner) at onset in patients' affected (p=0.009) eyes. Both RNFL and GCIPL were significantly lower in affected eyes at 6 months (p=0.012 and p=0.007) respectively compared to baseline. CONCLUSION: The GCIPL is probably more sensitive index of axonal loss than the RNFL in acute optic neuritis and could be a better index to detect neurodegeneration in multiple sclerosis. This can helpful in estimating early axonal loss and can potentially be used in therapeutic trials of neuroprotective drugs. PMID- 26856944 TI - Cholesterol and markers of cholesterol turnover in multiple sclerosis: relationship with disease outcomes. AB - Multiple sclerosis (MS) is a chronic central nervous system disease that is associated with progressive loss of myelin and subsequent axonal degeneration. Cholesterol is an essential component of mammalian cellular and myelin membranes. In this systematic review, we examined the relationship between levels of cholesterol and markers of cholesterol turnover in circulation and/or cerebrospinal fluid (CSF) and disease outcomes in adults with clinically isolated syndrome (CIS) or confirmed MS. Studies suggest that elevated levels of circulating low density lipoprotein cholesterol (LDL), total cholesterol, and particularly, apolipoprotein B and oxidized LDL are associated with adverse clinical and MRI outcomes in MS. These relationships were observed as early as CIS. The studies also suggest that oxysterols, cholesterol precursors, and apolipoprotein E may be markers of specific disease processes in MS, but more research is required to elucidate these processes and relationships. Taken together, the data indicate that cholesterol and markers of cholesterol turnover have potential to be used clinically as biomarkers of disease activity and may even be implicated in the pathogenesis of MS. PMID- 26856946 TI - An atypical case of acute disseminated encephalomyelitis associated with cytomegalovirus infection. AB - We present the case of a young man admitted to our hospital for persistent headache associated with fever, retrorbitary pain and vomiting, who rapidly developed encephalopathy with drowsiness, paraplegia, hypoesthesia with a D6 sensory level and urinary retention. Brain and spinal cord MRI revealed findings compatible with acute disseminated encephalomyelitis (ADEM) and microbiological tests documented a cytomegalovirus (CMV) infection. CMV infection is extraordinarily associated with ADEM, but must be included in microbiological tests, because early diagnosis and treatment ameliorate the neurological outcome. PMID- 26856947 TI - Regulatory T cell number in multiple sclerosis patients: A meta-analysis. AB - Regulatory T cells (Treg cells), defined as CD4(+) CD25(+) FoxP3(+) T cells by expression of CD4, high-affinity IL-2 receptor and the transcription factor, forkhead box P3 (FoxP3). They play a pivotal role in protecting individuals from autoimmunity and a growing body of evidence suggests their role in the prevention of multiple sclerosis development. However, there are discrepancies about the type of defect in the Treg cells of multiple sclerosis patients and especially whether the Treg number alteration could be contributed to multiple sclerosis pathogenesis. Indeed, whether low number of Treg cells can be a risk factor contributing to multiple sclerosis pathogenesis is the matter of debate and there is not any comprehensive agreement on it. Thus, the objective of this systematic review and meta-analysis was to precisely quantify the nature and magnitude of the association between Treg cell number and the risk ratio/odds ratio (OR) of multiple sclerosis in the case-control studies. Hence, medical databases of Embase, PubMed/Medline, PubMed, PubMed Central and SCOPUS were searched for empirical papers using "Regulatory T cell frequency", "Treg frequency" in combination with "multiple sclerosis". In the case-control studies, papers were reviewed for inclusion/exclusion criteria and 8 publications were included. Under random-effect model meta-analysis the data showed that the frequency of Treg cells was not a risk factor in multiple sclerosis using current laboratory methods. PMID- 26856948 TI - Important role of mast cells in multiple sclerosis. AB - Autoimmunity is a disease that occurs when the body tissue is attacked by its own immune system. Multiple sclerosis (MS) is an autoimmune illness which triggers neurological progressive and persistent functions. MS is associated with an abnormal B-cell response and upregulation of T-cell reactivity against a multitude of antigens. Mast cells are the first line of the innate immune system and act by degranulating and secreting chemical mediators and cytokines. Their participation on the central nervous system has been recognized since the beginning of the last century. They have an important role in autoimmune disease, including MS where they mediate inflammation and demyelinization by presenting myelin antigens to T cells or disrupting the blood-brain barrier and permitting entry of inflammatory cells and cytokines. The participation of mast cells in MS is demonstrated by gene overexpression of chemical mediators and inflammatory cytokines. Here we report the relationship and involvement between mast cells and multiple sclerosis. PMID- 26856949 TI - Reducing clinical trial risk in multiple sclerosis. AB - OBJECTIVE: To determine the risk of clinical trial failure for new drugs in multiple sclerosis (MS) and to identify factors that could improve outcomes. METHODS: We collected data on compounds that were tested in MS from Phase I to Phase III clinical trials between 1998 and January 2015. Clinical trials success rates were calculated and compared to industry standards. The exclusion criteria for the drugs in this study were: drugs that commenced Phase I in MS prior to 1998, non-industry conducted trials, trials testing non-disease modifying drug treatment, and trials testing combinations of drugs already approved by the FDA. RESULTS: Fifty-three distinct drugs met our inclusion criteria. The cumulative success rate for MS drugs was 27%, almost triple the 10% industry rate. Clinical trial success rates in MS surpass that of industry across all phases. Phase II clinical trials completed in a "Relapsing MS" population were most successful in predicting Phase III clinical trial success. Small molecules were found to have a higher overall success rate compared to biologics; however, both drug technologies largely pursue different molecular targets. Drugs that were previously FDA approved for another indication and were subsequently tested in MS had lower success rates than drugs that had no previous FDA approval history. CONCLUSIONS: Overall, MS enjoys almost triple the clinical trial success rates of other disease areas. In addition, small molecules are superior to biologics in MS and novel drugs are superior to drugs with a previous FDA approval history outside MS. PMID- 26856950 TI - A previously misdiagnosed cohort of aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder with disease duration of >10 years in multi-ethnic Penang, Malaysia: Clinical features and disease course. PMID- 26856951 TI - Effects of a virtual reality and treadmill training on gait of subjects with multiple sclerosis: a pilot study. AB - Gait and cognitive deficits are common in multiple sclerosis (MS) and are negatively affected during dual-task walking. Treadmill (TM) training has been previously used to preserve locomotor activity in MS. Virtual reality (VR) engages the user in cognitive and motor activities simultaneously. A training combining TM and VR has been successfully adopted in several neurological diseases, but not in MS. This study aims at investigating the feasibility of a VR based TM training program on gait of subjects with MS. Eight persons with relapsing-remitting MS were recruited to participate in a six-week VR-based TM training program. Gait analysis was performed both in single and dual task conditions. Clinical tests were used to assess walking endurance and obstacle negotiation. All the evaluations were performed before, immediately and one month after the training. Gait speed and stride length improved in dual task post intervention and were retained at follow-up. An improved ability in negotiating obstacles was found across the evaluations. VR-based TM training program is feasible and safe for MS subjects with moderate disabilities and may positively affect gait under complex conditions, such as dual tasking and obstacle negotiation. PMID- 26856953 TI - Editors' Welcome. PMID- 26856952 TI - Pooled safety and tolerability data from four placebo-controlled teriflunomide studies and extensions. AB - BACKGROUND: Teriflunomide, a once-daily oral immunomodulator for the treatment of relapsing-remitting multiple sclerosis, has demonstrated consistent efficacy on clinical and MRI parameters in clinical trials. OBJECTIVE: To summarize the safety and tolerability profile of teriflunomide based on data from four placebo controlled trials. METHODS: Safety and tolerability were assessed using two teriflunomide clinical program data pools. Pool 1 contained 3044 patients randomized to teriflunomide (14 mg or 7 mg) or placebo in the core studies of one phase 2 trial and three phase 3 trials, with cumulative treatment exposure >1500 patient-years per group. Pool 2 comprised 2338 patients who received teriflunomide treatment in the above trials, including those continuing in extension studies, with a duration of treatment up to 12 years, representing >6800 patient-years. Safety assessments included adverse events, laboratory parameters, and physical examinations. RESULTS: In Pool 1, the number of patients experiencing adverse events and serious adverse events was similar in the three treatment groups. Common events occurring in >= 10% of patients in either teriflunomide group, and with an incidence >= 2% compared with placebo, were alanine aminotransferase (ALT) increase, headache, diarrhea, hair thinning, and nausea. Overall, the nature of events observed in Pool 2 was similar to Pool 1. The majority of events in both pools were of mild-to-moderate intensity, were self-limiting, and infrequently resulted in discontinuation of therapy. The most common reason for treatment discontinuation in all treatment groups was ALT elevation, reflecting the protocol requirement to discontinue treatment on confirmation of ALT > 3 * the upper limit of normal. CONCLUSIONS: No new or unexpected safety signals beyond those detected in individual trials were identified in this pooled analysis with treatment duration exceeding 12 years and a cumulative exposure to teriflunomide exceeding 6800 patient-years. Overall, both doses of teriflunomide had consistent and manageable safety profiles. PMID- 26856954 TI - Late cardiac perforation following percutaneous sealing of a permeable foramen ovale. PMID- 26856955 TI - The prognostic value of lymph node ratio in a national cohort of rectal cancer patients. AB - OBJECTIVE: To analyze the prognostic implications of the lymph node ratio (LNR) in curative resected rectal cancer. SUMMARY BACKGROUND DATA: It has been proposed that the LNR has a high prognostic impact in colorectal cancer, but the lymph node ratio has not been evaluated exclusively for rectal cancer in a large national cohort study. METHODS: All 6793 patients in Denmark diagnosed with stage I to III adenocarcinoma of the rectum, and so treated in the period from 2003 to 2011, were included in the analysis. The cohort was divided into two groups according to whether or not neo-adjuvant treatment had been given. RESULTS: In a multivariate analysis the pN status, ypN status and lymph node yield were found to be independent prognostic factors for overall survival, irrespective of neo adjuvant therapy. The LNR was also found to be a significant prognostic factor with a Hazard Ratio ranging from 1.154 (95% CI: 0.930-1.432) (LNR: 0.01-0.08) to 2.974 (95% CI: 2.452-3.606) (LNR > 0.5) in the group of patients who had surgery to begin with and from 1.381 (95% CI: 0.891-2.139) (LNR: 0.01-0.08) to 2.915 (95% CI: 2.244-3.787) (LNR > 0.5) in the group of patients who had neo-adjuvant treatment. CONCLUSIONS: The LNR reflects the influence on survival from N-status and the lymph node yield and since LNR was shown to be a significant prognostic predictor for overall survival in patients with curatively resected stage III rectal cancer irrespective of neo-adjuvant therapy we recommend that the introduction of LNR should be considered for rectal cancer in a revised TNM classification. PMID- 26856956 TI - Preoperative CT and MRI prediction of non-resectability in patients treated for pseudomyxoma peritonei from mucinous appendiceal neoplasms. AB - AIMS: To evaluate computed tomography (CT) and magnetic resonance imaging (MRI) findings for sign of hepatoduodenal ligament and small bowel non-resectability in patients with pseudomyxoma peritonei (PMP) and to compare assessments made by the radiologist based on their experiences. METHODS: Between January 2009 and June 2014, all consecutive patients with PMP selected for curative surgery were scheduled to undergo CT and MRI examinations within two days of their surgery. Several imaging findings of hepatoduodenal ligament and small bowel involvements were retrospectively evaluated by a senior and a junior radiologist and compared with surgical findings. RESULTS: Of the 82 patients enrolled in the study, 11 had non-resectable lesions with hepatoduodenal ligament infiltration (n = 4) and/or extensive small bowel involvement (n = 9). All patients underwent CT and 73 underwent MRI scan. Infiltration of the adipose tissue of the hepatoduodenal ligament by mucinous tumor was associated with non-resectability. For the senior and junior radiologists, the sensitivity and specificity were 75% and 100%, and 50% and 100% on CT (kappa value (k) = 0.79); 67% and 100%, and 33% and 97% on MRI (k = 0.38), respectively. Diffuse involvement of the mesentery and/or the small bowel serosa was also associated with non-resectability. For the senior and junior radiologists, the sensitivity and specificity were 67% and 100%, and 56% and 99% on CT (k = 0.82); 88% and 100%, and 38% and 100% on MRI (k = 0.58), respectively. CONCLUSION: CT and MRI can both contribute to the diagnosis of non resectability in patients with PMP. The use of MRI to identify small bowel involvement, in particular, benefits from a more experienced radiologist. PMID- 26856957 TI - Short term and long term results of patients with colorectal liver metastases undergoing surgery with or without radiofrequency ablation. AB - PURPOSE: The combination of resection and radiofrequency ablation (RFA) may provide an alternative treatment for patients with unresectable colorectal liver metastases (CRLM). Although the results in literature look promising, uncertainty exists with regard to complication risks and survival for this therapy. METHODS: From January 2000 to May 2013, patients were included in a prospective multicenter database when treated for CRLM. Exclusion criteria were: two-staged treatment, synchronous resection of liver metastases and primary tumor, loss to follow-up or extrahepatic metastases. Patients were divided in a resection-only group (ROG) and combination group (CG). Outcome variables were retrospectively analyzed. RESULTS: In CG, 98 patients were included versus 534 patients in ROG. There were no differences in general patient characteristics. Patients in CG had a higher Fong clinical risk score (CRS; P = 0.001), better ASA classification (P = 0.04) and received more neoadjuvant chemotherapy (P = 0.001). There was no difference in postoperative morbidity or 90-day mortality. The 5-year disease free survival (DFS) for CG and ROG was 25% and 36.1% (P = 0.03), respectively. For the 5-year overall survival (OS) this was respectively 42% and 62.2% (P = 0.001). On multivariate analysis, Fong CRS was a significant predictor for DFS. For OS, Fong CRS, ASA class IV and the combination therapy were significant predictors. CONCLUSION: The combination of hepatic resection and intraoperative RFA is a safe procedure, without increase in postoperative morbidity or mortality. Combining RFA and resection in one session is a valid treatment option for patients who would otherwise be inoperable. PMID- 26856958 TI - Chemically Functionalized, Well-Dispersed Carbon Nanotubes in Lithium-Doped Zinc Oxide for Low-Cost, High-Performance Thin-Film Transistors. AB - Surface-functionalized carbon nanotubes (CNTs) are introduced into lithium-doped ZnO thin-film transistors (TFTs) as an alternative to the conventional incorporation of an expensive element, indium. The crucial role of surface functionalization of CNTs is clarified with the demonstration of indium-free ZnO based TFTs with a field-effect mobility of 28.6 cm(2) V(-1) s(-1) and an on/off current ratio of 9 * 10(6) for low-cost, high-performance electronics. PMID- 26856959 TI - Radiation Therapy Versus Radical Prostatectomy: A Never-ending Discussion. PMID- 26856960 TI - A Specific Mapping Study Using Fluorescence Sentinel Lymph Node Detection in Patients with Intermediate- and High-risk Prostate Cancer Undergoing Extended Pelvic Lymph Node Dissection. AB - : Sentinel lymph node (SLN) detection techniques have the potential to change the standard of surgical care for patients with prostate cancer. We performed a lymphatic mapping study and determined the value of fluorescence SLN detection with indocyanine green (ICG) for the detection of lymph node metastases in intermediate- and high-risk patients undergoing radical prostatectomy and extended pelvic lymph node dissection. A total of 42 patients received systematic or specific ICG injections into the prostate base, the midportion, the apex, the left lobe, or the right lobe. We found (1) that external and internal iliac regions encompass the majority of SLNs, (2) that common iliac regions contain up to 22% of all SLNs, (3) that a prostatic lobe can drain into the contralateral group of pelvic lymph nodes, and (4) that the fossa of Marcille also receives significant drainage. Among the 12 patients who received systematic ICG injections, 5 (42%) had a total of 29 lymph node metastases. Of these, 16 nodes were ICG positive, yielding 55% sensitivity. The complex drainage pattern of the prostate and the low sensitivity of ICG for the detection of lymph node metastases reported in our study highlight the difficulties related to the implementation of SNL techniques in prostate cancer. PATIENT SUMMARY: There is controversy about how extensive lymph node dissection (LND) should be during prostatectomy. We investigated the lymphatic drainage of the prostate and whether sentinel node fluorescence techniques would be useful to detect node metastases. We found that the drainage pattern is complex and that the sentinel node technique is not able to replace extended pelvic LND. PMID- 26856961 TI - The Peer and Family Smoking Index: A Valid Measure of Secondhand Smoke Exposure in Adolescents. AB - PURPOSE: Nearly half of all adolescents in the United States are exposed to secondhand smoke (SHS) daily, primarily at home, resulting in respiratory infections, asthma exacerbations, and reduced lung function. A concise self report measure is needed to identity adolescents exposed to SHS. The purpose of this study was to test whether nonsmoking adolescents who reported exposure to peer and/or family smoking on the Peer and Family Smoking Index had higher salivary cotinine levels than those reporting no exposure to either peer or family smoking. METHODS: A convenience sample of 135 English-speaking adolescents ages 15-18 years was recruited from two high schools. Those who reported use of nicotine replacement therapy, cigarette smoking (past 30 days), smokeless tobacco use (past 30 days), or who self-reported pregnancy were excluded. Salivary cotinine and self-report data from the Peer and Family Smoking Index were collected after obtaining parental consent and assent from the adolescent. RESULTS: Mean salivary cotinine levels differed by exposure group (none, family, peer, or family and peer), F (3, 130) = 5.44, p = .001. The post hoc analysis identified a significantly higher mean cotinine level among those exposed to SHS from both family and peers than among those with no exposure (p = .001). CONCLUSIONS: Known groups validity of the index was supported. Adolescents who reported family smoking or a combination of family and peer smoking had significantly higher salivary cotinine levels than unexposed adolescents. The Peer and Family Smoking Index is a concise and valid self-report measure for SHS exposure in adolescents. PMID- 26856964 TI - Effects of Single and Multiple Blood Pressure Measurement Strategies on the Prediction of Prevalent Screen-Detected Diabetes Mellitus: A Population-Based Survey. AB - The authors investigated the effects of single and multiple blood pressure (BP) measurements during the same encounter on screen-detected diabetes risk. Data for 9018 Cameroonian adults from a community-based survey were used. Resting BP was measured three times 5 minutes apart. Logistic regressions were used to compute the odd ratio (OR) per standard deviation (SD) higher BP variables. Systolic BP, diastolic BP, and mean arterial pressure (MAP), but not pulse pressure, were related to prevalent diabetes. The highest OR (95% confidence interval [CI]) per SD higher pressure were recorded for MAP (OR, 1.16; 95% CI, 1.05-1.28) and systolic BP (OR, 1.15; 95% CI, 1.04-1.27). Estimates of the association were highest for the first, then third, and lastly the second BP measurements. Estimates from average BP measurements were not better than those from single measurement. Single BP measurement is more effective for diabetes risk screening than multiple measurements. Community-based diabetes strategies utilizing a single measurement are simple without compromising the yield. PMID- 26856962 TI - Spherical subjective refraction with a novel 3D virtual reality based system. AB - PURPOSE: To conduct a clinical validation of a virtual reality-based experimental system that is able to assess the spherical subjective refraction simplifying the methodology of ocular refraction. METHODS: For the agreement assessment, spherical refraction measurements were obtained from 104 eyes of 52 subjects using three different methods: subjectively with the experimental prototype (Subj.E) and the classical subjective refraction (Subj.C); and objectively with the WAM-5500 autorefractor (WAM). To evaluate precision (intra- and inter observer variability) of each refractive tool independently, 26 eyes were measured in four occasions. RESULTS: With regard to agreement, the mean difference (+/-SD) for the spherical equivalent (M) between the new experimental subjective method (Subj.E) and the classical subjective refraction (Subj.C) was 0.034D (+/-0.454D). The corresponding 95% Limits of Agreement (LoA) were ( 0.856D, 0.924D). In relation to precision, intra-observer mean difference for the M component was 0.034+/-0.195D for the Subj.C, 0.015+/-0.177D for the WAM and 0.072+/-0.197D for the Subj.E. Inter-observer variability showed worse precision values, although still clinically valid (below 0.25D) in all instruments. CONCLUSIONS: The spherical equivalent obtained with the new experimental system was precise and in good agreement with the classical subjective routine. The algorithm implemented in this new system and its optical configuration has been shown to be a first valid step for spherical error correction in a semiautomated way. PMID- 26856963 TI - The relationship between the failure to eradicate Helicobacter pylori and previous antibiotics use. AB - BACKGROUND: The previous use of antibiotics is known to correlate positively with antibiotic resistance; whether this is also the case in the eradication of Helicobacter pylori infection is unclear. AIM: To investigate the relationship between the previous use of antibiotics and the failure of eradication therapy in H. pylori infection. METHODS: The relationship between the clinical parameters and the failure of H. pylori eradication was analyzed in patients administered standard triple therapy and then assessed for the eradication of H. pylori based on a C13-urea breath test. RESULTS: In a multivariate analysis, failure rates increased significantly in patients with a history of clarithromycin (odds ratio [OR], 4.445) or other macrolides (OR, 2.407) use, who were female (OR, 1.339), or who were older than 60 years of age (OR, 1.326). The eradication failure rate in patients with a history of macrolides use for >2 weeks was significantly higher than if the duration of use was <2 weeks (44.8% vs. 29.3%, p=0.047). CONCLUSIONS: A patient's history of macrolides is a useful predictor of the likelihood of standard triple therapy failure in H. pylori eradication. The alternatives such as a bismuth-based quadruple or a levofloxacin-containing therapy should be considered in patients treated with macrolides for >2 weeks. PMID- 26856966 TI - Changing and Differentiated Urban Landscape in China: Spatiotemporal Patterns and Driving Forces. AB - Urban landscape spatiotemporal change patterns and their driving mechanisms in China are poorly understood at the national level. Here we used remote sensing data, landscape metrics, and a spatial econometric model to characterize the spatiotemporal patterns of urban landscape change and investigate its driving forces in China between 1990 and 2005. The results showed that the urban landscape pattern has experienced drastic changes over the past 15 years. Total urban area has expanded approximately 1.61 times, with a 2.98% annual urban growth rate. Compared to previous single-city studies, although urban areas are expanding rapidly, the overall fragmentation of the urban landscape is decreasing and is more irregular and complex at the national level. We also found a stair stepping, urban-landscape changing pattern among eastern, central, and western counties. In addition, administrative level, urban size, and hierarchy have effects on the urban landscape pattern. We also found that a combination of landscape metrics can be used to supplement our understanding of the pattern of urbanization. The changes in these metrics are correlated with geographical indicators, socioeconomic factors, infrastructure variables, administrative level factors, policy factors, and historical factors. Our results indicate that the top priority should be strengthening the management of urban planning. A compact and congregate urban landscape may be a good choice of pattern for urban development in China. PMID- 26856965 TI - Dysfunction of subtelomeric methylation and telomere length in gallstone disease and gallbladder cancer patients of North Central India. AB - BACKGROUND: Telomeres play an important role in cancer progression. Recently it has been shown that subtelomeric methylation negatively regulates telomere length in various diseases, including cancers. Here, we evaluated the influence of subtelomeric methylation in telomere dysfunction in gallbladder cancer (GBC), and whether this dysfunction is affected by the presence of gallstones. METHODS: Relative telomere length and subtelomeric methylation levels were assessed using monochrome multiplex quantitative polymerase chain reaction and bisulfite sequencing, respectively, in different gallbladder tissue types including different grades of GBC, gallstones and adjacent non-tumor. RESULTS: We found telomere length to shorten significantly in overall GBC, but specifically in early grade cancer. We also found D4Z4 and DNF92 subtelomeric sequences to be hypermethylated and hypomethylated, respectively, in GBC; however, their methylation levels differed significantly, only in early grade cancer. We could not find any specific correlation between subtelomeric methylation and telomere length in GBC. Interestingly, telomere length and subtelomeric methylation differed significantly in GBC without gallstones but not in GBC with gallstones. CONCLUSIONS: This study, thus, suggests that telomere dysfunction and changes in methylation levels may occur earlier in the progression of GBC, while the presence of gallstones may have no influence on telomere length as well as on methylation levels. PMID- 26856967 TI - The Hepatitis C virus treatment cascade at an urban postincarceration transitions clinic. AB - Transitions clinics, which provide medical care to individuals who have been released from incarceration, reach a population at high risk for hepatitis C Virus (HCV) infection. We used the HCV treatment cascade to describe HCV care at an urban postincarceration transitions clinic, identifying gaps in care and determining reasons for lapses in care. In this retrospective cohort study, we reviewed electronic health records for all formerly incarcerated individuals receiving care at the Bronx Transitions Clinic. HCV treatment cascade measures included the following: detection of HCV antibodies, confirmation of chronic infection, specialist referral, specialist evaluation, initiation of treatment, completion of treatment and achievement of SVR. We recorded reasons for lapses in care. Of 451 patients accessing care, 317 (70%) were screened for HCV antibodies, and 106 (33%) tested positive. Of the 106 antibody-positive patients, 93 (88%) were evaluated for HCV viremia and 84 (79%) were confirmed to have chronic HCV infection; 19% of the total sample had chronic HCV infection. Of these 84 with chronic HCV, 48 (57%) received specialist referral, 30 (36%) were evaluated, 8 (10%) initiated treatment, and 5 (6%) completed treatment and achieved SVR. Some treatment lapses occurred because patients were deemed unstable for treatment (12%) or were re-incarcerated (5%). Chronic HCV infection was common among transitions clinic patients. Few were treated and cured. Patients lost contact with providers before consideration for antiviral therapy. Referral to specialty providers was a gap in care. Increasing HCV treatment in this population will likely require intensive delivery models. PMID- 26856968 TI - Discriminatory value of carotid artery elasticity changes for the evaluation of thyroid dysfunction in patients with hashimoto's thyroiditis. AB - PURPOSE: To evaluate the discriminatory value of carotid artery wall thickness and elasticity for thyroid dysfunction in Hashimoto's thyroiditis (HT) patients. METHODS: A total of 180 female HT patients were assigned to three groups on the basis of laboratory testing: HT hyperthyroidism group (group A), HT hypothyroidism group (group B), and HT euthyroid group (group C). We used radiofrequency sonographic signal analysis for the measurement of intima-media thickness and arterial stiffness. RESULTS: Intima-media thickness was significantly higher in group A than in other groups. After stepwise variable selection, distensibility coefficient (DC), compliance coefficient, stiffness index (beta), and pulse wave velocity (PWV) were selected to discriminate different thyroid hormone levels, resulting in the following discriminant function: Z1 = -0.398DC + 0.803PWV. The receiver-operator characteristic curve analysis showed that the critical points were DC = 0.022 kPa(-1) and PWV = 5.36 m/s for HT hyperthyroidism, and DC = 0.016 kPa(-1) and PWV = 6.875 m/s for HT hypothyroidism. CONCLUSIONS: DC and PWV may be useful for the evaluation of thyroid function in HT patients. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:298-304, 2016. PMID- 26856969 TI - Intrathecal Ziconotide: Dosing and Administration Strategies in Patients With Refractory Chronic Pain. AB - INTRODUCTION: Ziconotide is a non-opioid analgesic for intrathecal (IT) administration. The aim of this review is to provide a comprehensive and clinically relevant summary of the literature on dosing and administration with IT ziconotide in the management of refractory chronic pain, and to describe novel dosing strategies intended to improve clinical outcomes. MATERIALS AND METHODS: A Medline search was conducted for "ziconotide," supplemented by manual searching of published bibliographies and abstracts from conferences. RESULTS: Early experience with IT ziconotide in clinical trials combined with improved understanding of drug pharmacokinetics in the cerebrospinal fluid have led to a reappraisal of approaches to trialing and initiation of continuous-infusion therapy in an effort to improve tolerability. The traditional paradigm of trialing by inpatient continuous infusion may be shifting toward outpatient trialing by IT bolus, although definitions of success and specific protocols remain to be agreed upon. Expert consensus on IT continuous infusion with ziconotide suggests a starting dose of 0.5 to 1.2 mcg/day followed by dose titration of <=0.5 mcg/day on a no more than weekly basis, according to individual patients' pain reductions and regimen tolerability. DISCUSSION: Newer modalities that include patient-controlled analgesia and nocturnal flex dosing have been shown to hold promise of further improvements in ziconotide efficacy and tolerability. CONCLUSIONS: Clinical trials and experience confirm the feasibility and usefulness of IT ziconotide in the management of refractory chronic pain. Emerging evidence suggests that additional IT delivery options may further expand the usefulness and benefits of ziconotide. PMID- 26856970 TI - Acute myeloid leukaemia: expression of MYC protein and its association with cytogenetic risk profile and overall survival. AB - Acute myeloid leukaemia (AML) is a clinically aggressive disease with marked genetic heterogeneity. Cytogenetic abnormalities provide the basis for risk stratification into clinically favourable, intermediate, and unfavourable groups. There are additional genetic mutations, which further influence the prognosis of patients with AML. Most of these result in molecular aberrations whose downstream target is MYC. It is therefore logical to study the relationship between MYC protein expression and cytogenetic risk groups. We studied MYC expression by immunohistochemistry in a large cohort (n = 199) of AML patients and correlated these results with cytogenetic risk profile and overall survival (OS). We illustrated differential expression of MYC protein across various cytogenetic risk groups (p = 0.03). Highest expression of MYC was noted in AML patients with favourable cytogenetic risk group. In univariate analysis, MYC expression showed significant negative influence of OS in favourable and intermediate cytogenetic risk group (p = 0.001). Interestingly, MYC expression had a protective effect in the unfavourable cytogenetic risk group. In multivariate analysis, while age and cytogenetic risk group were significant factors influencing survival, MYC expression by immunohistochemistry methods also showed some marginal impact (p = 0.069). In conclusion, we have identified differential expression of MYC protein in relation to cytogenetic risk groups in AML patients and documented its possible impact on OS in favourable and intermediate cytogenetic risk groups. These preliminary observations mandate additional studies to further investigate the routine clinical use of MYC protein expression in AML risk stratification. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26856971 TI - Walter (Wally) Burgdorf, M.D., 1943-2015. PMID- 26856972 TI - Liver capsule: Molecular-based signatures in hepatocellular carcinoma. PMID- 26856973 TI - Introduction to the special issue on Clostridium difficile and the history of the International Clostridium difficile Symposium (ICDS). PMID- 26856974 TI - Effect of Body Mass Index on Outcomes in Left Ventricular Assist Device Recipients. AB - BACKGROUND AND AIM: Obesity is associated with higher mortality following heart transplantation, but there remains no consensus regarding outcomes in left ventricular assist device (LVAD) recipients. We sought to determine the impact of body mass index (BMI) on outcomes in patients undergoing LVAD implantation. METHODS: This was a single-institution retrospective review, including all patients who received a HeartMate II LVAD or HeartWare HVAD between March 2006 and June 2014. Patients were stratified into three groups based on normal (<25 kg/m(2) ), overweight (25-30 kg/m(2) ), and obese (>30 kg/m(2) ) BMI. RESULTS: Two hundred patients were included in the analysis. Mean BMI was 28.3 kg/m(2) , (27% normal, 36% overweight, and 36.5% obese). Obese patients were younger (51.9 years, p = 0.03) and had higher incidence of diabetes (58.9% vs. 24.1%; p < 0.001) and peripheral vascular disease (16.4% vs. 1.9%; p = 0.03). Normal BMI patients were more likely to undergo LVAD implantation as destination therapy compared to the overweight and obese groups (67% vs. 39% vs. 51%; p = 0.01) and had higher incidence of postoperative stroke/transient ischemic attack (22.2% vs. 6.9% vs. 12.3%; p = 0.04) and postoperative bleeding requiring reoperation (27.8% vs. 12.5% vs. 9.6%; p = 0.01). Survival at one, three, and five years was similar across all BMI groups. BMI was not an independent predictor of overall survival. CONCLUSIONS: Appropriately-selected patients at the extremes of BMI can safely undergo LVAD implantation with no difference in survival. BMI should not in itself be considered a contraindication to LVAD placement. PMID- 26856975 TI - 'Ring-within-a-ring' appearance: morphological clue to topical steroid abuse in dermatophytosis. PMID- 26856976 TI - The importance of age, sex and place in understanding socioeconomic inequalities in allostatic load: Evidence from the Scottish Health Survey (2008-2011). AB - BACKGROUND: Given the broad spectrum of health and wellbeing outcomes that are patterned by socioeconomic position (SEP), it has been suggested that there may be common biological pathways linking SEP and health. Allostatic load is one such pathway, which aims to measure cumulative burden/dysregulation across multiple physiological systems. This study aimed to determine the contextual and demographic factors (age, sex and place) that may be important in better understanding the links between lower SEP and higher allostatic load. METHODS: Data were from a nationally representative sample of adults (18+): the Scottish Health Survey (2008-2011). Higher SEP ('1') was defined as having 'Higher'-level, secondary school qualifications versus having lower level or no qualifications ('0'). For allostatic load, a range of 10 biomarkers across the cardiovascular, metabolic and immune systems were used. Respondents were scored "1" for each biomarker that fell into the highest quartile of risk. Linear regressions were run in STATA, including SEP, age (continuous and as a 7-category variable), sex (male/female), urbanity (a 5-category variable ranging from primary cities to remote rural areas) and geographical location (based on 10 area-level healthboards). Interactions between SEP and each predictor, as well as stratified analyses, were tested. RESULTS: Lower SEP was associated with higher allostatic load even after adjusting for age, sex and place (b = -0.631, 95 % CI -0.795, 0.389, p < 0.001). There was no significant effect moderation between SEP and age, sex or place. Stratified analysis did show that the inequality identified in the baseline models widened with age, becoming significant at ages 35-44, before narrowing at older ages (75+). There was no difference by sex, but more mixed findings with regards place (urbanity or geographical location), with a mix of significant and non-significant results by SEP that did not appear to follow any pattern. CONCLUSIONS: Inequalities in allostatic load by educational attainment, as a measure of SEP, are consistent with age, sex and place. However, these stratified analyses showed that these inequalities did widen with age, before narrowing in later life, matching the patterns seen with other objective and subjective health measures. However, effect moderation analysis did not support evidence of a statistically significant interaction between age and SEP. Context remains an important feature in understanding and potentially addressing inequalities, although may be less of an issue in terms of physiological burden. PMID- 26856977 TI - Days spent in acute care hospitals at the end of life of cancer patients in four Swiss cantons: a retrospective database study (SAKK 89/09). AB - Number of days spent in acute hospitals (DAH) at the end of life is regarded as an important care quality indicator for cancer patients. We analysed DAH during 90 days prior to death in patients from four Swiss cantons. Claims data from an insurance provider with about 20% market share and patient record review identified 2086 patients as dying of cancer. We calculated total DAH per patient. Multivariable generalised linear modelling served to evaluate potential explanatory variables. Mean DAH was 26 days. In the multivariable model, using complementary and alternative medicine (DAH = 33.9; +8.8 days compared to non users) and canton of residence (for patient receiving anti-cancer therapy, Zurich DAH = 22.8 versus Basel DAH = 31.4; for other patients, Valais DAH = 22.7 versus Ticino DAH = 33.7) had the strongest influence. Age at death and days spent in other institutions were additional significant predictors. DAH during the last 90 days of life of cancer patients from four Swiss cantons is high compared to most other countries. Several factors influence DAH. Resulting differences are likely to have financial impact, as DAH is a major cost driver for end-of-life care. Whether they are supply- or demand-driven and whether patients would prefer fewer days in hospital remains to be established. PMID- 26856978 TI - Use of diagnosis codes for detection of clinically significant opioid poisoning in the emergency department: A retrospective analysis of a surveillance case definition. AB - BACKGROUND: Although fatal opioid poisonings tripled from 1999 to 2008, data describing nonfatal poisonings are rare. Public health authorities are in need of tools to track opioid poisonings in near real time. METHODS: We determined the utility of ICD-9-CM diagnosis codes for identifying clinically significant opioid poisonings in a state-wide emergency department (ED) surveillance system. We sampled visits from four hospitals from July 2009 to June 2012 with diagnosis codes of 965.00, 965.01, 965.02 and 965.09 (poisoning by opiates and related narcotics) and/or an external cause of injury code of E850.0-E850.2 (accidental poisoning by opiates and related narcotics), and developed a novel case definition to determine in which cases opioid poisoning prompted the ED visit. We calculated the percentage of visits coded for opioid poisoning that were clinically significant and compared it to the percentage of visits coded for poisoning by non-opioid agents in which there was actually poisoning by an opioid agent. We created a multivariate regression model to determine if other collected triage data can improve the positive predictive value of diagnosis codes alone for detecting clinically significant opioid poisoning. RESULTS: 70.1 % of visits (Standard Error 2.4 %) coded for opioid poisoning were primarily prompted by opioid poisoning. The remainder of visits represented opioid exposure in the setting of other primary diseases. Among non-opioid poisoning codes reviewed, up to 36 % were reclassified as an opioid poisoning. In multivariate analysis, only naloxone use improved the positive predictive value of ICD-9-CM codes for identifying clinically significant opioid poisoning, but was associated with a high false negative rate. CONCLUSIONS: This surveillance mechanism identifies many clinically significant opioid overdoses with a high positive predictive value. With further validation, it may help target control measures such as prescriber education and pharmacy monitoring. PMID- 26856979 TI - A group matrix representation relevant to scales of measurement of clinical disease states via stratified vectors. AB - BACKGROUND: Previously, we applied basic group theory and related concepts to scales of measurement of clinical disease states and clinical findings (including laboratory data). To gain a more concrete comprehension, we here apply the concept of matrix representation, which was not explicitly exploited in our previous work. METHODS: Starting with a set of orthonormal vectors, called the basis, an operator Rj (an N-tuple patient disease state at the j-th session) was expressed as a set of stratified vectors representing plural operations on individual components, so as to satisfy the group matrix representation. RESULTS: The stratified vectors containing individual unit operations were combined into one-dimensional square matrices [Rj]s. The [Rj]s meet the matrix representation of a group (ring) as a K-algebra. Using the same-sized matrix of stratified vectors, we can also express changes in the plural set of [Rj]s. The method is demonstrated on simple examples. CONCLUSIONS: Despite the incompleteness of our model, the group matrix representation of stratified vectors offers a formal mathematical approach to clinical medicine, aligning it with other branches of natural science. PMID- 26856981 TI - Physical health and well-being: Experiences and perspectives of young adult mental health consumers. AB - Compromised physical health and raised levels of morbidity and mortality are experienced by young people (16-24 years) with mental illness, and are compounded by psychotropic medication. How this group conceives and experiences physical health is not well understood. We investigated the meanings, beliefs, and endeavours of young people that impact their physical health understandings and behaviours. The present study formed the qualitative phase of a sequential mixed methods study, and incorporated semistructured interviews with 12 hospitalized young people. Qualitative content analysis was used to analyse data. Participants held a holistic ideal of physical health that they did not meet. Weight change, poor sleep, and limited exercise adversely impacted their lives and self-image. Sedentary behaviour, reduced energy, and limited health literacy compromised effective management of physical health. Young people needed structure and support to assist them in addressing their physical health needs when amotivation overwhelmed their internal resources. Nurses are well placed to help young people increase their competency for health management. Individualized information and methods to promote good physical health are required for this group in jeopardy from physical morbidity and mortality. PMID- 26856980 TI - Insight to changing morphologic patterns of glomerulopathy in adult Pakistani patients: an institutional perspective. AB - BACKGROUND: Idiopathic nephrotic syndrome encompasses diverse histogenetic patterns and depicts socioeconomic and demographic differences attributable to genetic profile, environmental factors and prevalence of infectious diseases. A lack of renal registry in our country necessitates a need to document changing histologic patterns of nephrotic syndrome as noted in different parts of the world. METHODS: We retrospectively analyzed 140 patients who underwent renal biopsy at Liaquat National Hospital from January 2009 to December 2013 over a period of 3 years. On the basis of clinical profile cases were segregated into nephritic and nephrotic syndrome and histologic and immunoflourescence findings were analyzed. RESULTS: Among 140 cases of glomerulonephritis diagnosed in the study period, 98 cases (70 %) were those of primary glomerulonephritis and 42 were of secondary glomerulopathy (30 %). Membranous glomerulonephritis was the most common primary glomerulonephritis (33.6 %) followed by focal segmental glomerulosclerosis FSGS (20.4 %), whereas lupus nephritis is the most common secondary glomerulopathy (47.6 %) followed by amyloidosis and diabetic glomerulosclerosis (16.6 % each). CONCLUSION: We found a considerable high incidence of membranous glomerulonephritis and FSGS in our population that entails a need to investigate prevalence of associated factors like Hepatitis B and HIV infections in population at risk. Moreover, renal biopsy registry would be instrumental in this regard to record changing disease pattern in this part of the world. PMID- 26856982 TI - Arthrodesis of the Subtalar Joint in a High School Football Player With a Talocalcaneal Coalition: Case Report With Functional Analysis. AB - : Tarsal coalition is a bony or fibrous bridge between 2 tarsal bones. The condition is typically congenital and presents in early to mid-adolescence. Common symptoms include ankle pain, stiffness, and limited range of motion. Conservative treatment of tarsal coalition consists of immobilization, short leg walking cast, steroid injections, physical therapy, ankle braces, and orthotics. When conservative care fails, surgical intervention for tarsal coalition includes excision of the coalition or joint arthrodesis. We present a case of a high school football player with a 5-year history of left ankle pain secondary to a talocalcaneal coalition. The athlete did not respond favorably to conservative treatment and underwent a subtalar joint arthrodesis. Prior to surgery, the athlete consented to self-reported functional outcome measures, range of motion measures, and 3D video gait analysis to evaluate the effects of surgery. Measurements were taken prior to surgery and 11/2 years after surgery. Clinically significant improvements were seen in subjective outcome measures and functional ankle range of motion in this case. There is limited research available to validate long-term outcomes for current conservative and surgical treatments of tarsal coalition. In this case, joint arthrodesis resulted in a good long-term outcome for this athlete. LEVELS OF EVIDENCE: Therapeutic, Level IV: Case study. PMID- 26856983 TI - Gutter Impingement in Total Ankle Arthroplasty. AB - Gutter pain and impingement are recognized entities following total ankle arthroplasty (TAA). However, little concrete information is available in the existing literature regarding the etiology, potentiating factors, treatment and prevention of gutter disease. This comprehensive monograph discusses this problem in expansive detail and provides insight to surgeons who perform TAA, such that these complications can be minimized in the future. LEVELS OF EVIDENCE: Level V: Expert opinion. PMID- 26856984 TI - Technique Tip: The Use of Cannulated Drill as a Tamp to Remove Loose Cannulated Screws. AB - Subtalar arthrodesis is considered to be the gold standard surgical solution for end-stage subtalar joint arthrosis. Although subtalar joint fusion rates are high, nonunion has been reported to range from 0% to 43%. Revision subtalar arthrodesis regardless of etiology often requires removal of loose hardware in soft bone. The inability of screw threads to engage bone may result in longer operative time, frustration for the surgeon, and potential negative outcome for the patient. We describe a novel technique in which a cannulated drill bit is used as a tamp to remove subtalar arthrodesis screws. We have found this method to be efficient and safe and transferable to any extremity. LEVELS OF EVIDENCE: Therapeutic, Level V: Expert opinion. PMID- 26856985 TI - Technique Tip: Novel Use of a Targeting Drill Guide for Syndesmotic Screw Placement. AB - Ankle fractures are among the most common traumatic injuries encountered by orthopaedic surgeons, but obtaining anatomic syndesmosis fixation can be difficult. Previous authors have described the centroidal axis of the syndesmosis. Our group has developed a novel technique of aligning the tibia and fibula along their anatomic centroidal axis using a targeting guide, which has showed good results in 1 patient at 1-year follow-up. LEVELS OF EVIDENCE: Level V: Expert opinion. PMID- 26856986 TI - Anatomic Repair of Plantar Plate With Flexor Tendon Sheath Reinforcement: Case Series. AB - Plantar plate pathology has gained considerable attention in recent time, and with this increased awareness multiple treatments have been proposed. There have been no comparison studies between these treatments. The authors feel a direct approach for anatomic repair allows for plantar plate repair and tightening to desired tension, without any plantar prominences or potentially irritating hardware. In addition if the plantar plate is found to be attenuated or there is a lack of residual tissue, the described imbrication utilizing the flexor digitorum longus sheath, which is not possible with hardware or newest instrumentation, allows for a robust repair. The presented case series provides results from consecutive patients treated with proposed concurrent plantar and dorsal incisions, providing proof of concept and viability of novel technique. LEVELS OF EVIDENCE: Level V: Case series. PMID- 26856987 TI - Salt depletion syndrome as the initial presentation of cystic fibrosis in a toddler with the rare p.Ala309Gly (A309G) CFTR variant. PMID- 26856988 TI - Neuroprotective effect of asiatic acid on rotenone-induced mitochondrial dysfunction and oxidative stress-mediated apoptosis in differentiated SH-SYS5Y cells. AB - Parkinson's disease (PD) is a chronic neurodegenerative disease, manifested due to the loss of dopaminergic neurons, which ultimately leads to impaired movement in elderly populations. The pathogenesis of PD is associated with numerous factors including oxidative stress, mitochondrial dysfunction and apoptosis. There is no effective therapy available to cure or halt the progression of this disease still now. Asiatic acid (AA) is a triterpene extracted from Centella asiatica has been reported as an antioxidant and anti-inflammatory agent, that offers neuroprotection against glutamate toxicity. Therefore, in this study, we have investigated the effect of AA in a rotenone (an inhibitor of mitochondrial complex I) induced in vitro model of PD. Following the exposure of SH-SY5Y cells to rotenone, there was a marked overproduction of ROS, mitochondrial dysfunction (as indexed by the decrease in mitochondrial membrane potential) and apoptosis (Hoechst and dual staining, comet assay; expressions of pro-apoptotic and anti apoptotic indices). Pre-treatment with AA reversed these changes might be due to its antioxidant, mitoprotective and anti-apoptotic properties. However further extensive studies on in vivo models of PD are warranted to prove AA neuroprotective effect before entering into the clinical trial. PMID- 26856989 TI - LRG1 modulates epithelial-mesenchymal transition and angiogenesis in colorectal cancer via HIF-1alpha activation. AB - BACKGROUND: Leucine-rich-alpha-2-glycoprotein 1 (LRG1) has been reported to be involved in several tumors, whether it participates in colorectal cancer (CRC) progression remains unclear. Here, we investigated the biological function and underlying molecular mechanisms of LRG1 in CRC. METHODS: The mRNA and protein levels of LRG1 were assessed in CRC tissues through RT-PCR and immunohistochemistry, respectively. HCT116 and SW480 cells were treated with LRG1 siRNA, control siRNA, or recombinant LRG1. Transwell invasion assays and wound healing assays were performed to evaluate the invasion and migration of CRC cells. Epithelial-to-mesenchymal transition (EMT) markers of E-cadherin, VDR, N cadherin, alpha-SMA, Vimentin and Twist1 were detected by RT-PCR and western blot. Enzyme-linked immunosorbent assay was used to measure the secretion level of VEGF-A. Conditioned medium from CRC cells was collected for endothelial cell migration, tube formation and aortic ring sprouting assays. RESULTS: LRG1 was overexpressed in CRC tissues and associated with cancer aggressiveness. LRG1 was further found to induce the EMT process, as well as CRC cell migration and invasion capacity. In addition, LRG1 promoted VEGF-A expression in CRC cells and contributed to tumor angiogenesis. Furthermore, HIF-1alpha could be induced by LRG1 in a concentration- and time-dependent manner, which was responsible for LRG1-induced VEGF-A expression and EMT. CONCLUSIONS: The present study suggests that LRG1 plays a crucial role in the progression of CRC by regulating HIF-1alpha expression, thereby may be a promising therapeutic target of CRC. PMID- 26856990 TI - Residual small artery impairment in hypertensive patients with normal albumin creatinine ratio. AB - Objectives Previous studies have suggested that urine albumin excretion (UAE) mirrors generalized vascular damage; however, it is unclear to which degree UAE mirrors small artery impairment. Design We enrolled 67 patients with uncomplicated essential hypertension (EH) during stable antihypertensive therapy. F-Rmin, ACR on three non-consecutive morning urine samples, pulse wave velocity (PWV), and 24-h ambulatory blood pressure (ABPM) were measured. Results ACR was low (0.39 and 0.30-0.60), but abnormal small artery structure defined as F-Rmin > mean + 2 standard deviations of normotensive value (1.99 + 1 mmHg min/(ml/100 ml)) was present in 45% (n = 30). The mean F-Rmin was 2.89 +/- 0.09 mmHg min/(ml/100 ml). ACR correlated significantly to PWV (r(2 )=( )0.11; p < 0.05) and pulse pressure (r(2 )=( )0.15; p < 0.001), but not F-Rmin and (r(2 )=( )0.05, p = 0.07). Conclusions Abnormal microvascular structure was present even in EH patients with low UAE. ACR correlated to arterial stiffness and not to small artery structure; therefore, UEA did not reflect microvascular damage in this population. ACR and F-Rmin thus reflect two distinct types of subclinical organ damage in hypertension. PMID- 26856991 TI - Generation of data on within-subject biological variation in laboratory medicine: An update. AB - In recent decades, the study of biological variation of laboratory analytes has received increased attention. The reasons for this interest are related to the potential practical applications of such knowledge. Biological variation data allow the derivation of important parameters for the interpretation and use of laboratory tests, such as the index of individuality for the evaluation of the utility of population reference intervals for the test interpretation, the estimate of significant change in a timed series of results of an individual, the number of specimens required to obtain an accurate estimate of the homeostatic set point of the analyte and analytical performance specifications that assays should fulfill for their application in the clinical setting. It is, therefore, essential to experimentally derive biological variation information in an accurate and reliable way. Currently, a dated guideline for the biological variation data production and a more recent checklist to assist in the correct preparation of publications related to biological variation studies are available. Here, we update and integrate, with examples, the available guideline for biological variation data production to help researchers to comply with the recommendations of the checklist for drafting manuscripts on biological variation. Particularly, we focus on the distribution of the data, an essential aspect to be considered for the derivation of biological variation data. Indeed, the difficulty in deriving reliable estimates of biological variation for those analytes, the measured concentrations of which are not normally distributed, is more and more evident. PMID- 26856992 TI - Diarrhea caused by multiparasitic infection. AB - Diarrhoea caused by multiple nematode infection is uncommon in Spain, therefore we are not very familiar with the diagnosis and treatment of these patients. PMID- 26856993 TI - A matter of time: study of circadian clocks and their role in inflammation. AB - Circadian rhythms regulate changes in physiology, allowing organisms to respond to predictable environmental demands varying over a 24 h period. A growing body of evidence supports a key role for the circadian clock in the regulation of immune functions and inflammatory responses, which influence the understanding of infections and inflammatory diseases and their treatment. A variety of experimental methods have been used to assess the complex bidirectional crosstalk between the circadian clock and inflammation. In this review, we summarize the organization of the molecular clock, experimental methods used to study circadian rhythms, and both the inflammatory and immune consequences of circadian disturbance. PMID- 26856994 TI - Secondary allergic T cell responses are regulated by dendritic cell-derived thrombospondin-1 in the setting of allergic eye disease. AB - Allergic eye disease, as in most forms of atopy, ranges in severity among individuals from immediate hypersensitivity to a severe and debilitating chronic disease. Dendritic cells play a key role in stimulating pathogenic T cells in allergen re-exposure, or secondary responses. However, molecular cues by dendritic cells underpinning allergic T cell response levels and the impact that this control has on consequent severity of allergic disease are poorly understood. Here, we show that a deficiency in thrombospondin-1, a matricellular protein known to affect immune function, has subsequent effects on downstream T cell responses during allergy, as revealed in an established mouse model of allergic eye disease. More specifically, we demonstrate that a thrombospondin-1 deficiency specific to dendritic cells leads to heightened secondary T cell responses and consequent clinical disease. Interestingly, whereas thrombospondin 1-deficient dendritic cells augmented activity of allergen-primed T cells, this increase was not recapitulated with naive T cells in vitro. The role of dendritic cell-derived thrombospondin-1 in regulating secondary allergic T cell responses was confirmed in vivo, as local transfer of thrombospondin-1-sufficient dendritic cells to the ocular mucosa of thrombospondin-1 null hosts prevented the development of augmented secondary T cell responses and heightened allergic eye disease clinical responses. Finally, we demonstrate that topical instillation of thrombospondin-1-derived peptide reduces T cell activity and clinical progression of allergic eye disease. Taken together, this study reveals an important modulatory role of dendritic cell-derived thrombospondin-1 on secondary allergic T cell responses and suggests the possible dysregulation of dendritic cell derived thrombospondin-1 expression as a factor in allergic eye disease severity. PMID- 26856997 TI - The year urban health was r/deconstructed. PMID- 26857000 TI - To what extent are medicinal plants shared between country home gardens and urban ones? A case study from Misiones, Argentina. AB - Context Worldwide ethnobotanical research has shown the importance of home gardens as sources of medicinal plants. These resources are worthy of further study in the Argentinean Atlantic Forest due to the richness of medicinal flora and their importance for local people. Objective We studied richness, composition, cultural importance and medicinal uses of plants in home gardens of rural, semirural and urban areas in the Iguazu Department (Misiones, Argentina). Our hypothesis claims that people living in different environments have a similar array of medicinal plants in their gardens and they use them in a similar way. Materials and methods The analysis was based on 76 interviews and plant inventories of home gardens. During guided walks in gardens, voucher specimens were collected. To analyse composition, Simpson similarity index was applied and a new index was proposed to measure culturally salient species. Results All the environments had similar species composition with species differing in less than 30% of them. The most culturally salient taxa were Mentha spicata L. (Lamiaceae), in rural, Artemisia absinthium L. (Asteraceae), in semirural, and Aloe maculata All. (Xanthorrhoeaceae), in urban areas. The body systems treated with medicinal plants were similar across study sites. Discussion The results suggest a "core repertoire" of medicinal plants and a widespread exchange of plants among local population. The cultural importance index informs us about plant adaptability, based on the efficacy and the versatility of medicinal resources. Conclusion In this changing context where mobility and migrations constitute everyday life, medicinal plants in home gardens are part of local healthcare sovereignty. PMID- 26856999 TI - Cytotoxic and genotoxic assessment of surface water from Sao Paulo State, Brazil, during the rainy and dry seasons. AB - The aim of this study was to determine if the cytotoxic and genotoxic responses of Allium cepa are effective biomarkers of harmful effects caused by polluted river water and if changes in the responses reflect seasonality in the harmful effects. Samples were collected in the dry season (August 2011 and 2012) and rainy season (February 2012 and 2013) at sampling points on the Jaguari River and the Ribeirao Lavapes, in Brazil. Allium cepa bulbs were exposed to the samples, to positive controls (15 ug/L methyl methanesulfonate), and to negative controls (tap water). Three root tips from each bulb were then stained using the Feulgen reaction, then the micronucleus frequency, the mitotic index, and mitotic anomalies were measured. The total number of anomalies (stickiness, c-mitosis, multipolarity, chromosome bridges, and unidentified anomalies) in the rainy season (8.61 +/- 3.65) and dry season (7.07 +/- 2.96) were significantly different (U = 11.31, p = 0.04). Toxicity, indicated by the formation of micronuclei and the mitotic index, was higher in the February 2012 samples than in the August 2012 samples. The mean manganese concentration (0.13 mg/L) in the rainy season samples was higher than the maximum concentration permitted by the Brazilian National Environmental Council (<0.1 mg/L) and the manganese concentrations positively correlated with chromosomal aberration induction (p = 0.01, r = 0.69). In conclusion, the rainy season samples were more toxic than the dry season samples. This was probably related to rain water carrying compounds with potentially negative impacts into the rivers. These findings highlight the importance of biomonitoring studies and of treating wastewater in urban areas. PMID- 26856996 TI - Harnessing the potential of community-based participatory research approaches in bipolar disorder. AB - BACKGROUND: Despite the rapid growth in the sophistication of research on bipolar disorder (BD), the field faces challenges in improving quality of life (QoL) and symptom outcomes, adapting treatments for marginalized communities, and disseminating research insights into real-world practice. Community-based participatory research (CBPR)-research that is conducted as a partnership between researchers and community members-has helped address similar gaps in other health conditions. This paper aims to improve awareness of the potential benefits of CBPR in BD research. METHODS: This paper is a product of the International Society for Bipolar Disorders (ISBD) Taskforce on Community Engagement which includes academic researchers, healthcare providers, people with lived experience of BD, and stakeholders from BD community agencies. Illustrative examples of CBPR in action are provided from two established centres that specialize in community engagement in BD research: the Collaborative RESearch Team to study psychosocial issues in BD (CREST.BD) in Canada, and the Spectrum Centre for Mental Health Research in the United Kingdom. RESULTS AND DISCUSSION: We describe the philosophy of CBPR and then introduce four core research areas the BD community has prioritized for research: new treatment approaches, more comprehensive outcome assessments, tackling stigma, and enhanced understanding of positive outcomes. We then describe ways in which CBPR is ideal for advancing each of these research areas and provide specific examples of ways that CBPR has already been successfully applied in these areas. We end by noting potential challenges and mitigation strategies in the application of CBPR in BD research. CONCLUSIONS: We believe that CBPR approaches have significant potential value for the BD research community. The observations and concerns of people with BD, their family members, and supports clearly represent a rich source of information. CBPR approaches provide a collaborative, equitable, empowering orientation to research that builds on the diversity of strengths amongst community stakeholders. Despite the potential merits of this approach, CBPR is as yet not widely used in the BD research field, representing a missed opportunity. PMID- 26856995 TI - CFTR: A New Horizon in the Pathomechanism and Treatment of Pancreatitis. AB - Cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that conducts chloride and bicarbonate ions across epithelial cell membranes. Mutations in the CFTR gene diminish the ion channel function and lead to impaired epithelial fluid transport in multiple organs such as the lung and the pancreas resulting in cystic fibrosis. Heterozygous carriers of CFTR mutations do not develop cystic fibrosis but exhibit increased risk for pancreatitis and associated pancreatic damage characterized by elevated mucus levels, fibrosis, and cyst formation. Importantly, recent studies demonstrated that pancreatitis causing insults, such as alcohol, smoking, or bile acids, strongly inhibit CFTR function. Furthermore, human studies showed reduced levels of CFTR expression and function in all forms of pancreatitis. These findings indicate that impairment of CFTR is critical in the development of pancreatitis; therefore, correcting CFTR function could be the first specific therapy in pancreatitis. In this review, we summarize recent advances in the field and discuss new possibilities for the treatment of pancreatitis. PMID- 26857001 TI - [Palliative surgery in visceral medicine. Exemplified by colorectal and gastric cancer]. AB - BACKGROUND: The benefits of primary tumor resection in metastatic disease remains a matter of debate. Existing data are almost exclusively limited to results from retrospective analyses. Data from prospective, randomized trials are currently not available. AIM: The results from two prospective observational studies involving gastric and rectal cancer patients are presented and discussed in the context of the available literature. METHOD: Based on data collected within the prospective quality assurance studies on gastric and rectal cancer conducted by the Institute for Quality Assurance in Surgery at Otto von Guericke University, Magdeburg, Germany, the long-term outcome after palliative primary tumor resection in patients with International Union Against Cancer (UICC) stage IV rectal cancer (2005-2008, n = 2046) and metastatic gastric cancer (2007-2009, n = 687) was analyzed and compared to published data. RESULTS: The median survival time following palliative primary tumor resection of UICC stage IV rectal cancer in the patients analyzed was 20 months. In patients with hepatic metastases undergoing metastasectomy the median survival was 38 months. This increased to 58 months for patients with lymph node negative primary tumors. In metastatic gastric cancer patients undergoing palliative (R2) gastric resection and also patients not undergoing surgery showed a prognostic benefit from palliative chemotherapy; however, the median survival time was significantly prolonged if palliative chemotherapy was preceded by resection of the primary tumor (11 versus 7 months, p < 0.001). DISCUSSION: Together with previously published data, the results from the two observational studies on rectal and gastric cancer presented here suggest a prognostic benefit from palliative resection of the primary tumor in metastatic disease. PMID- 26857002 TI - [Surgery for metastases, anatomical and ethical limits. Special aspect: oligometastases]. AB - The surgical resection of metastases is nowadays feasible in selected patients with multifocal metastatic disease due to the implementation of interdisciplinary multimodal therapeutic options. Anatomical limitations do not seem to represent obstacles which cannot be overcome because of the development of new surgical techniques. The cornerstone of the selection of patients is the correct staging diagnosis achieved through modern diagnostic tools; however, surgery alone does not always offer acceptable survival and recurrence-free rates. Furthermore, in every complex surgical procedure there is the risk of morbidity and mortality; therefore, parameters such as alternative therapeutic modalities, the individual situation of the patient and tumor biology have to be considered in order to make the correct selection of patients. This is one of the major future challenges and should never be driven by unfounded hopes and expectations of the patients. The same principle also applies for brain metastases, which represent the most common brain tumors. Approximately 70 % of patients with brain metastases have 1-3 lesions (oligometastases). Treatment is now individualized and the goal of therapy has shifted towards long-term survival (>= 24 months) and improved quality of life. Under this aspect surgery is one of the important treatment options, particularly in patients with a single metastasis or oligometastases. Furthermore, approximately 20 % of patients who have recurrent brain metastases, successfully undergo a complete resection of tumors and with a Karnofsky performance status (KPS) score > 70 show a long-term survival of >= 24 months. PMID- 26857003 TI - A review of neurotoxicity of microcystins. AB - Cyanobacterial blooms-produced microcystins are secondary metabolites which can accumulate in the food chain and contaminate water, thus posing a potential threat to the health of aquatic animals and even humans. Microcystin toxicity affects not only the liver but also the other organs, i.e., the brain. The serious neurotoxicity effects caused by microcystins then lead to various symptoms. This review focuses on the neurotoxicity of microcystins. Microcystins can cross blood-brain barrier with the transport of Oatps/OATPs, causing neurostructural, functional, and behavioral changes. In this review, potential uptake mechanisms and neurotoxicity mechanisms are summarized, including neurotransmissions, neurochannels, signal transduction, oxidative stress, and cytoskeleton disruption. However, further researches are needed for detailed studies on signaling pathways and the downstream pathways of neurotoxicity of microcystins. PMID- 26857004 TI - Spatial monitoring of heavy metals in the inland waters of Serbia: a multispecies approach based on commercial fish. AB - The study monitored the contamination of fish muscle tissue by elements Al, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb, and Zn at 17 sampling sites, in order to assess the pollution status of the main rivers in Serbia. Of the six commercially important fish species included in the study (pikeperch Sander lucioperca, catfish Silurus glanis, bream Abramis brama, barbel Barbus barbus, chub Squalius cephalus, nase Chondrostoma nasus), the bioconcentration factor (BCF) indicated that benthivore bream and barbel and predatory catfish have the highest tendency toward the accumulation of elements. This study achieved its primary objective and produced a contamination map of Serbia as a basis for further research. The estimated metal pollution index (MPI) showed the Tisa River to be unaffected by direct pollution (with an MPI value of 0.31) and the West Morava and Pek rivers to be affected (with MPI values of 1.92 and 0.73 for the WM1 and WM2 sampling sites and 0.65 for the Pek sampling site). Over the past two decades, Serbia has not expanded its industrial activity, which has resulted in the barely noticeable anthropogenic input of heavy metals in the rivers close to industry, and the main rivers are mostly unaffected and slightly affected. We assumed that pollution by heavy metals in the 1990s was trapped in the sediment, thus showing an increased concentration of elements in the species that live and feed on the bottom. Hg concentrations exceeded the maximum permitted concentrations (MPCs) only in catfish samples (0.62 mg kg(-1)) from the Danube (D3 sampling site) and barbel (0.78 mg kg(-1)) from the West Morava (WM1 sampling site), while Cd concentrations exceeded the MPC in catfish samples (0.09 mg kg(-1)) from the Danube (D1 sampling site) and chub samples (0.1 mg kg(-1)) from the South Morava (SM2 sampling site). The average concentrations of Pb exceeded the MPC in chub and barbel samples (0.32 and 0.82 mg kg(-1), respectively) from the West Morava (WM1 sampling site); chub, barbel, and nase samples (0.35, 0.32, 0.31 mg kg(-1), respectively) from the West Morava (WM2 sampling site); chub and barbel samples (0.35 and 0.3 mg kg(-1), respectively) from the Ibar; chub samples (0.39 mg kg( 1)) from the Drina; chub and barbel samples (0.59 and 0.4 mg kg(-1), respectively) from the Great Timok; and nase samples (0.33 mg kg(-1)) from the Pek. These results demonstrate that there is a need for future studies that would involve similar analyses and focus especially on smaller rivers that have been neglected so far. PMID- 26857005 TI - Multivariate co-integration analysis of the Kaya factors in Ghana. AB - The fundamental goal of the Government of Ghana's development agenda as enshrined in the Growth and Poverty Reduction Strategy to grow the economy to a middle income status of US$1000 per capita by the end of 2015 could be met by increasing the labour force, increasing energy supplies and expanding the energy infrastructure in order to achieve the sustainable development targets. In this study, a multivariate co-integration analysis of the Kaya factors namely carbon dioxide, total primary energy consumption, population and GDP was investigated in Ghana using vector error correction model with data spanning from 1980 to 2012. Our research results show an existence of long-run causality running from population, GDP and total primary energy consumption to carbon dioxide emissions. However, there is evidence of short-run causality running from population to carbon dioxide emissions. There was a bi-directional causality running from carbon dioxide emissions to energy consumption and vice versa. In other words, decreasing the primary energy consumption in Ghana will directly reduce carbon dioxide emissions. In addition, a bi-directional causality running from GDP to energy consumption and vice versa exists in the multivariate model. It is plausible that access to energy has a relationship with increasing economic growth and productivity in Ghana. PMID- 26857006 TI - Application of response surface methodology to optimize the operational parameters for enhanced removal efficiency of organic matter and nitrogen: moving bed biofilm reactor. AB - An attempt of response surface methodology (RSM) has been made for more effective utilization and optimization for considerable reduction of operational conditions such as reaction time, aeration time, energy consumption, etc. for municipal wastewater treatment process using moving bed biofilm reactor (MBBR). A mathematical-statistical model was developed for the second-order response surface through the fit of a polynomial function and a central composite design (CCD) in the form of a full factorial design. CCD was employed to assess the interactive effects of the three main independent operational parameters, including biocarrier filling rate (0-70 %), aeration rate (0.21-0.42 m(3) h(-1)), and reactor run time (1-15 days), on the removal efficiency of chemical oxygen demand (COD), biochemical oxygen demand (BOD), and total Kjeldahl nitrogen (TKN). Analysis of variance expressed a high coefficient of determination (R (2) = 0.84 0.95), thereby indicating that the model is significant. Using a desirability function for the highest COD (93 %), BOD (96 %), and TKN (69 %) removal, the optimum carrier filling rate, aeration rate, and reactor run time were identified to be 40 %, 0.21 m(3) h(-1), and 7 days, respectively. It shows that RSM can be a suitable method to optimize the operational parameters of MBBR with enhanced removal efficiency and less power consumption. PMID- 26857008 TI - Development and Validation of a High Anatomical Fidelity FE Model for the Buttock and Thigh of a Seated Individual. AB - Current practices for designing new cushions for seats depend on superficial measurements, such as pressure mapping, which do not provide sufficient information about the condition of sub-dermal tissues. Finite element (FE) modelling offers a unique alternative to integrate assessment of sub-dermal tissue condition into seat/cushion design and development processes. However, the development and validation of such FE models for seated humans requires accurate representation of the anatomy and material properties, which remain challenges that are yet to be addressed. This paper presents the development and validation of a detailed 3D FE model with high anatomical fidelity of the buttock and thigh, for a specific seated subject. The developed model consisted of 28 muscles, the pelvis, sacrum, femur, and one layer of inter-muscular fat, subcutaneous fat and skin. Validation against in vivo measurements from MRI data confirmed that the FE model can simulate the deformation of soft tissues under sitting loads with an accuracy of (mean +/- SD) 4.7 +/- 4.4 mm. Simulation results showed that the maximum strains (compressive, shear and von-Mises) on muscles (41, 110, 79%) were higher than fat tissues (21, 62, 41%). The muscles that experienced the highest mechanical loads were the gluteus maximus, adductor magnus and muscles in the posterior aspect of the thighs (biceps femoris, semitendinosus and semimembranosus muscles). The developed FE model contributes to the progression towards bio-fidelity in modelling the human body in seated postures by providing insight into the distribution of stresses/strains in individual muscles and inter muscular fat in the buttock and thigh of seated individuals. Industrial applications for the developed FE model include improving the design of office and household furniture, automotive and airplane seats and wheelchairs as well as customisation and assessment of sporting and medical equipment to meet individual requirements. PMID- 26857007 TI - Two-Point Stretchable Electrode Array for Endoluminal Electrochemical Impedance Spectroscopy Measurements of Lipid-Laden Atherosclerotic Plaques. AB - Four-point electrode systems are commonly used for electric impedance measurements of biomaterials and tissues. We introduce a 2-point system to reduce electrode polarization for heterogeneous measurements of vascular wall. Presence of endoluminal oxidized low density lipoprotein (oxLDL) and lipids alters the electrochemical impedance that can be measured by electrochemical impedance spectroscopy (EIS). We developed a catheter-based 2-point micro-electrode configuration for intravascular deployment in New Zealand White rabbits. An array of 2 flexible round electrodes, 240 um in diameter and separated by 400 um was microfabricated and mounted on an inflatable balloon catheter for EIS measurement of the oxLDL-rich lesions developed as a result of high-fat diet-induced hyperlipidemia. Upon balloon inflation, the 2-point electrode array conformed to the arterial wall to allow deep intraplaque penetration via alternating current (AC). The frequency sweep from 10 to 300 kHz generated an increase in capacitance, providing distinct changes in both impedance (Omega) and phase (phi) in relation to varying degrees of intraplaque lipid burden in the aorta. Aortic endoluminal EIS measurements were compared with epicardial fat tissue and validated by intravascular ultrasound and immunohistochemistry for plaque lipids and foam cells. Thus, we demonstrate a new approach to quantify endoluminal EIS via a 2-point stretchable electrode strategy. PMID- 26857009 TI - Is the robotic approach feasible for repair of iatrogenic injuries of the lower ureter? AB - OBJECTIVES: To analyze the robotic approach as treatment of iatrogenic ureteral injuries. METHODS: Medical records were reviewed for patients undergoing robotic assisted laparoscopic ureteral reimplantation at the University of Missouri from 2009 to 2014. Patient charts were analyzed for demographics, prior abdominal surgeries, circumstances of injury, outcomes, and other relevant information. RESULTS: Nine patients met inclusion criteria. The average age was 44.6. Patients had an average of 4.3 abdominal surgeries. Injury occurred during hysterectomy (open, laparoscopic, or vaginal) in eight patients (88.9 %), five cases were laparoscopic, two utilized robotic assistance, and one injury occurred during uterosacral vault suspension. All cases were related to gynecological procedures. On average, ureteral injury was detected 17.2 days after the initial surgery and repaired 62.3 days after initial operation. The average surgical repair time was 295.9 min (range 168-498) with an average blood loss of 77.2 mL (range 20-150). Four patients required a psoas hitch, with one receiving both a psoas hitch and a Boari flap. Postoperatively, patients had an average hospital stay of 2.7 days. One patient had ileus for greater than 3 days, and another was readmitted within 30 days for pain control and antiemetics following stent removal. One patient underwent open reimplantation 3 years after original surgery for development of ureteral stricture. At follow-up, all patients had returned to baseline renal function. CONCLUSIONS: Robotic approach is feasible and a safe option for distal iatrogenic ureteral injuries occurring during gynecological procedures. Prior abdominal surgery or delayed repair does not preclude a robotic approach. PMID- 26857010 TI - Molecular phylogenetic confirmation of Gnathostoma spinigerum Owen, 1836 (Nematoda: Gnathostomatidae) in Laos and Thailand. PMID- 26857011 TI - Food restriction during pregnancy alters brain's antioxidant network in dams and their offspring. AB - Dietary restriction increases life span and protects distinct organisms against a series of diseases, among which, those related to oxidative stress, like neurodegenerative diseases. Interferences in the maternal environment are known to reprogram the offspring metabolism response, impacting in the risk of chronic diseases development in adulthood. We aimed to assess the effects of 40% food restriction on reactive species levels, enzymatic and non-enzymatic antioxidant defenses, and oxidative damage parameters in the cerebellum and total cerebral cortex of pregnant rats and their offspring. Dams and pups showed oxidative modulation caused by food restriction in both structures. Dichlorofluorescein oxidation, reflecting reactive species levels, was reduced in the cerebellum of dams and offspring, while the cerebral cortex was not affected. Decreased mitochondrial superoxide levels were found in the cerebellum and cerebral cortex of pups, while nitric oxide was increased in the cortex. We also measured the activities of important antioxidant enzymes responsible by reactive oxygen species elimination. Superoxide dismutase activity was increased in the cerebellum of dams and in both structures of pups, while it was decreased in dams' cerebral cortex. Both brain structures were affected concerning to catalase, glutathione peroxidase, and glutaredoxin activities, which were reduced in pups and dams. Non-enzymatic defenses were decreased in pups, while dams showed an adaptive pattern in the cerebellum and no alteration in the cerebral cortex. Even though the results suggest increased oxidative status, lipids and proteins were not oxidatively affected. Our data suggest that intrauterine food restriction may disrupt oxidative status, impairing the antioxidant network. PMID- 26857014 TI - Relative Effects of Fluid Oscillations and Nutrient Transport in the In Vitro Growth of Valvular Tissues. AB - Engineered valvular tissues are cultured dynamically, and involve specimen movement. We previously demonstrated that oscillatory shear stresses (OSS) under combined steady flow and specimen cyclic flexure (flex-flow) promote tissue formation. However, localized efficiency of specimen mass transport is also important in the context of cell viability within the growing tissues. Here, we investigated the delivery of two essential species for cell survival, glucose and oxygen, to 3-dimensional (3D) engineered valvular tissues. We applied a convective-diffusive model to characterize glucose and oxygen mass transport with and without valve-like specimen flexural movement. We found the mass transport effects for glucose and oxygen to be negligible for scaffold porosities typically present during in vitro experiments and non-essential unless the porosity was unusually low (<40%). For more typical scaffold porosities (75%) however, we found negligible variation in the specimen mass fraction of glucose and oxygen in both non-moving and moving constructs (p > 0.05). Based on this result, we conducted an experiment using bone marrow stem cell (BMSC)-seeded scaffolds under Pulsatile flow-alone states to permit OSS without any specimen movement. BMSC seeded specimen collagen from the pulsatile flow and flex-flow environments were subsequently found to be comparable (p > 0.05) and exhibited some gene expression similarities. We conclude that a critical magnitude of fluid-induced, OSS created by either pulsatile flow or flex-flow conditions, particularly when the oscillations are physiologically-relevant, is the direct, principal stimulus that promotes engineered valvular tissues and its phenotype, whereas mass transport benefits derived from specimen movement are minimal. PMID- 26857012 TI - Human monocytes undergo functional re-programming during differentiation to dendritic cell mediated by human extravillous trophoblasts. AB - Maternal immune adaptation is required for a successful pregnancy to avoid rejection of the fetal-placental unit. Dendritic cells within the decidual microenvironment lock in a tolerogenic profile. However, how these tolerogenic DCs are induced and the underlying mechanisms are largely unknown. In this study, we show that human extravillous trophoblasts redirect the monocyte-to-DC transition and induce regulatory dendritic cells. DCs differentiated from blood monocytes in the presence of human extravillous trophoblast cell line HTR-8/SVneo displayed a DC-SIGN(+)CD14(+)CD1a(-) phenotype, similar with decidual DCs. HTR8 conditioned DCs were unable to develop a fully mature phenotype in response to LPS, and altered the cytokine secretory profile significantly. Functionally, conditioned DCs poorly induced the proliferation and activation of allogeneic T cells, whereas promoted CD4(+)CD25(+)Foxp3(+) Treg cells generation. Furthermore, the supernatant from DC and HTR-8/SVneo coculture system contained significant high amount of M-CSF and MCP-1. Using neutralizing antibodies, we discussed the role of M-CSF and MCP-1 during monocyte-to-DCs differentiation mediated by extravillous trophoblasts. Our data indicate that human extravillous trophoblasts play an important role in modulating the monocyte-to-DC differentiation through M CSF and MCP-1, which facilitate the establishment of a tolerogenic microenvironment at the maternal-fetal interface. PMID- 26857015 TI - Clinical Immersion and Biomedical Engineering Design Education: "Engineering Grand Rounds". AB - Grand Rounds is a ritual of medical education and inpatient care comprised of presenting the medical problems and treatment of a patient to an audience of physicians, residents, and medical students. Traditionally, the patient would be in attendance for the presentation and would answer questions. Grand Rounds has evolved considerably over the years with most sessions being didactic-rarely having a patient present (although, in some instances, an actor will portray the patient). Other members of the team, such as nurses, nurse practitioners, and biomedical engineers, are not traditionally involved in the formal teaching process. In this study we examine the rapid ideation in a clinical setting to forge a system of cross talk between engineers and physicians as a steady state at the praxis of ideation and implementation. PMID- 26857017 TI - Autoimmune and Lymphoproliferative Complications of Common Variable Immunodeficiency. AB - Common variable immunodeficiency (CVID) is frequently complicated by the development of autoimmune and lymphoproliferative diseases. With widespread use of immunoglobulin replacement therapy, autoimmune and lymphoproliferative complications have replaced infection as the major cause of morbidity and mortality in CVID patients. Certain CVID complications, such as bronchiectasis, are likely to be the result of immunodeficiency and are associated with infection susceptibility. However, other complications may result from immune dysregulation rather than immunocompromise. CVID patients develop autoimmunity, lymphoproliferation, and granulomas in association with distinct immunological abnormalities. Mutations in transmembrane activator and CAML interactor, reduction of isotype-switched memory B cells, expansion of CD21 low B cells, heightened interferon signature expression, and retained B cell function are all associated with both autoimmunity and lymphoproliferation in CVID. Further research aimed to better understand that the pathological mechanisms of these shared forms of immune dysregulation may inspire therapies beneficial for multiple CVID complications. PMID- 26857016 TI - Immediate and Delayed Hypersensitivity Reactions to Corticosteroids: Evaluation and Management. AB - Corticosteroids are anti-inflammatory medications used widely to treat allergic inflammation. Although the endocrine and gastrointestinal side effects of corticosteroids have been described, the occurrence of immediate hypersensitivity reactions and delayed contact dermatitis due to corticosteroids remains under recognized. Hypersensitivity reactions can occur to a corticosteroid itself, or to the additives and vehicles in corticosteroid preparations. Skin testing and oral graded challenge can help confirm the suspected culprit agent in immediate hypersensitivity reactions and help identify an alternative tolerated corticosteroid. Patch testing can help identify the culprit agents in delayed hypersensitivity contact dermatitis. Cross-reactivity patterns have not been observed for immediate hypersensitivity reactions as they have been for delayed contact dermatitis. Sensitization in contact dermatitis exhibits cross-reactivity patterns based on corticosteroid structure. We review the current understanding regarding the clinical presentation, evaluation, and management of immediate and delayed hypersensitivity reactions to corticosteroids. PMID- 26857019 TI - Sonar sound groups and increased terminal buzz duration reflect task complexity in hunting bats. AB - More difficult tasks are generally regarded as such because they demand greater attention. Echolocators provide rare insight into this relationship because biosonar signals can be monitored. Here we show that bats produce longer terminal buzzes and more sonar sound groups during their approach to prey under presumably more difficult conditions. Specifically, we found Daubenton's bats, Myotis daubentonii, produced longer buzzes when aerial-hawking versus water-trawling prey, but that bats taking revolving air- and water-borne prey produced more sonar sound groups than did the bats when taking stationary prey. Buzz duration and sonar sound groups have been suggested to be independent means by which bats attend to would-be targets and other objects of interest. We suggest that for attacking bats both should be considered as indicators of task difficulty and that the buzz is, essentially, an extended sonar sound group. PMID- 26857018 TI - Mast Cells and Anaphylaxis. AB - For half a century, it has been known that the mast cell is the cell responsible for the majority of anaphylactic events. Its mediators, taken as a whole, are capable of producing all of the clinical manifestations of these events. With the discovery of immunoglobulin E (IgE), it was originally felt that the vast majority of anaphylactic episodes were due to antigen coupling with two cell bound IgE molecules. More recently it has been learned that many episodes are produced by direct activation of mast cells, not involving antigen binding to IgE, and that monomeric IgE under certain conditions can also cause degranulation. Of note--in regard to antigen independent degranulation--are recent reports that the human G-protein-coupled receptor, MRGPRX2, may be the receptor for many drugs and cationic proteins capable of producing direct mast cell degranulation and anaphylactic events. PMID- 26857020 TI - Galectin-8 promotes regulatory T-cell differentiation by modulating IL-2 and TGFbeta signaling. PMID- 26857021 TI - A molecular nanodevice for targeted degradation of mRNA during protein synthesis. AB - RNase H is an endonuclease that catalyzes the cleavage of RNA. Because it only acts on RNA in RNA:DNA hybrids, RNase H can be used for targeted degradation of RNA when used in combination with antisense oligodeoxyribonucleotides (ASODNs) designed against a specific sequence of the target RNA. In this study, ASODN and RNase H were co-conjugated on magnetic nanoparticles. The resulting nanoparticles, having integrated functions of probing and processing target RNA, were able to remove target mRNA sequences more effectively than free ASODNs. The paramagnetic property of the nanoparticles also enabled timed engagement and disengagement of the RNA-degrading components in a given system, and these nanoparticles were able to be used for ON/OFF control of gene expression during cell-free protein synthesis reactions. PMID- 26857022 TI - The prognostic impact of serum testosterone during androgen-deprivation therapy in patients with metastatic prostate cancer and the SRD5A2 polymorphism. AB - BACKGROUND: Although testosterone suppression during androgen-deprivation therapy (ADT) and obesity have been reported to affect ADT efficacy, there are few comprehensive analyses on the impact on ADT outcome. Recently, we demonstrated that the SRD5A2 polymorphism was associated with metastatic prostate cancer prognosis. Therefore, in this study, we investigated the relationship between ADT serum testosterone levels or body mass index (BMI) and the prognosis among men treated with primary ADT for metastatic prostate cancer. In addition, we examined the association of serum testosterone levels during ADT with the SRD5A2 polymorphism. METHODS: This study included 96 Japanese patients with metastatic prostate cancer. The relationship between clinicopathological parameters, including serum testosterone levels during ADT and BMI, and progression-free survival, overall survival and survival from progression following primary ADT treatment for metastatic prostate cancer was examined. Additionally, the association between the SRD5A2 gene polymorphism (rs523349) and serum testosterone levels during ADT was examined in 86 cases. RESULTS: Among clinicopathological parameters, the lowest quartile of serum testosterone levels during ADT was a significant predictor of better overall survival as well as survival from castration resistance. However, BMI was not associated with prognosis. The CC allele in the SRD5A2 gene (rs523349), encoding the less active 5alpha-reductase, was associated with lower serum testosterone levels during ADT. CONCLUSIONS: Taken together, these findings revealed a dramatic suppression of serum testosterone by ADT was associated with better survival among men with metastatic prostate cancer that have undergone primary ADT, which may be affected by the SRD5A2 gene polymorphism. PMID- 26857024 TI - Association between statins and clinical outcomes among men with prostate cancer: a systematic review and meta-analysis. PMID- 26857023 TI - Non-surgically related causes of erectile dysfunction after bilateral nerve sparing radical prostatectomy. AB - BACKGROUND: Erectile dysfunction (ED) represents one of the most common long-term side effects in prostate cancer (PCa) patients treated with bilateral nerve sparing radical prostatectomy (BNSRP). The aim of our study was to assess the influence of non-surgically related causes of ED in patients treated with BNSRP. METHODS: Overall, 716 patients treated with BNSRP were retrospectively identified. All patients had complete data on erectile function (EF) assessed by the Index of Erectile Function-EF domain (IIEF-EF) and depressive status assessed by the Center for Epidemiologic Studies-Depression (CES-D) questionnaire. EF recovery was defined as an IIEF-EF of ?22. Kaplan-Meier analyses assessed the impact of preoperative IIEF-EF, depression and adjuvant radiotherapy (aRT) on the time to EF recovery. Multivariable Cox regression models were used to test the impact of aRT on EF recovery after accounting for depression and baseline IIEF EF. RESULTS: Median follow-up was 48 months. Patients with a preoperative IIEF-EF of ?22 had substantially higher EF recovery rates compared with those with a lower IIEF-EF (P<0.001). Patients with a CES-D of <16 had significantly higher EF recovery rates compared to those with depression (60.8 vs 49.2%; P=0.03). Patients receiving postoperative aRT had lower rates of EF compared with their counterparts left untreated after surgery (40.7 vs 59.8%; P<0.001). These results were confirmed in multivariable analyses, where preoperative IIEF-EF (P<0.001), depression (P=0.04) and aRT (P=0.03) were confirmed as significant predictors of EF recovery. CONCLUSIONS: Preoperative functional status and depression should be considered when counseling PCa patients regarding the long-term side effects of BNSRP. Moreover, the administration of aRT has a detrimental effect on the probability of recovering EF after BNSRP. This should be taken into account when balancing the potential benefits and side effects of multimodal therapies in PCa patients. PMID- 26857025 TI - New Approaches to Reduce Readmissions in Patients With Heart Failure. PMID- 26857026 TI - Response to the Letter Entitled "Archegonous Cystic Odontoma Is Not Necessarily Primordial" by Ide et al. PMID- 26857027 TI - Health Care Professionals and the Employment-Related Needs of Cancer Survivors. AB - Introduction Individuals diagnosed with cancer look to health care professionals as primary sources of information. This positions staff in oncology settings in an ideal role to inform patients, who continue workforce participation in increasing numbers, about resources that might help them to handle work-related issues related to their oncological symptoms. This article reports on findings from a survey of staff that provide nonmedical services to cancer patients in two Houston area hospital systems. The impetus for this survey was two-fold: the trend in recent years for increasing numbers of cancer survivors to stay in the workforce after or even during treatment, and low levels of awareness that these employees are eligible for protection under the Americans with Disabilities Act of 1990 and its 2008 amendments (ADA Amendments Act of 2008, Pub. L. 110-325, 122 Stat. 3553, 2008; Americans with Disabilities Act, 42 U.S.C. S 12111-17, 2006). The survey assesses perceptions of the effects of cancer on patients' employment status, levels of knowledge about supports to address these employment-related needs, and respondents' preferred modes for information receipt. The latter topic serves the purpose of tailoring training activities to the respondents' informational needs and learning preferences. Methods Data were collected via an online survey administered in two Houston-area hospital systems. This article reports on the findings from 86 respondents. Results Tenure as measured by years in oncology is related positively to level of knowledge about disability-related benefits, legislation and programs (r = .32, P < .01). Respondents with more years in their profession worked with patients whom they reported had a higher number of cancer side effects that "created work difficulties for patients" (r = .24, P < .05). The number of side effects was in turn positively associated with negative effects of the diagnosis at work (r = .27, P < .05). A higher score of negative effects of the cancer diagnosis at work in turn correlated with unwanted consequences of disclosing the cancer at work (r = .36, P < .01). No statistically significant correlations were observed among the variables measuring respondents' reported knowledge of disability-related benefits, laws and programs, their perception of patients' level of understanding of these topics, and reports of patients' receipt of reasonable accommodation. Conclusions Health care professionals who treat cancer patients could benefit from training resources about how survivors might address their employment-related needs, including how to convey that knowledge to their patients. Mentoring programs might also have positive outcomes, since respondents with greater tenure in oncology-related settings reported higher levels of knowledge about disability related topics. PMID- 26857029 TI - A novel copper-rich open-framework chalcogenide constructed from octahedral Cu4Se6 and icosahedral Cu8Se13 nanoclusters. AB - We demonstrated a unique copper-rich open-framework chalcogenide constructed from icosahedral Cu8Se13 and octahedral Cu4Se6 nanoclusters connected to each other through a SnSe3(Se2) bridging unit. The specific copper-rich composition gives rise to a narrow band gap and photoelectrical responsive properties in the infrared range. PMID- 26857028 TI - Bidirectional associations between rheumatoid arthritis and depression: a nationwide longitudinal study. AB - Rheumatoid arthritis (RA) and depression may be associated with each other pathophysiologically, but few studies have been conducted on the interplay between these two diseases using longitudinal measurement. Therefore, we used the National Health Insurance Research Database of Taiwan to investigate the bidirectional associations between RA and depression. One cohort was included to analyze RA predicting the onset of depression and a second cohort for analysis of depression predicting RA. A sex- and age-matched control group was included for both. The incidence of depression in RA subjects was higher than in non-RA subjects [15.69 vs. 8.95 per 1,000 person-years (PYs)], with an adjusted hazard ratios (HRs) of 1.69 [95% confidence interval (CI), 1.51-1.87]. The incidence of RA was higher in depressed than non-depressed individuals (2.07 vs. 1.21 per 1,000 PYs), with an adjusted HRs of 1.65 (95% CI, 1.41-1.77). This population based cohort study suggested strong bidirectional relationships between RA and depression. Healthcare providers are recommended to facilitate the implementation of more effective therapeutic interventions to achieve favorable prognosis, especially for those with new-onset or younger cases. PMID- 26857030 TI - Speak Up! Addressing the Paradox Plaguing Patient-Centered Care. PMID- 26857031 TI - Computational studies of the binding profile of phosphoinositide PtdIns (3,4,5) P3 with the pleckstrin homology domain of an oomycete cellulose synthase. AB - Saprolegnia monoica is a model organism to investigate Saprolegnia parasitica, an important oomycete which causes considerable loss in aquaculture every year. S. monoica contains cellulose synthases vital for oomycete growth. However, the molecular mechanism of the cellulose biosynthesis process in the oomycete growth is still poorly understood. Some cellulose synthases of S. monoica, such as SmCesA2, are found to contain a plecsktrin homology (PH) domain, which is a protein module widely found in nature and known to bind to phosphoinositides, a class of signaling compounds involved in many biological processes. Understanding the molecular interactions between the PH domain and phosphoinositides would help to unravel the cellulose biosynthesis process of oomycetes. In this work, the binding profile of PtdIns (3,4,5) P3, a typical phosphoinositide, with SmCesA2-PH was studied by molecular docking, molecular dynamics and metadynamics simulations. PtdIns (3,4,5) P3 is found to bind at a specific site located at beta1, beta2 and beta1-beta2 loop of SmCesA2-PH. The high affinity of PtdIns (3,4,5) P3 to SmCesA2-PH is contributed by the free phosphate groups, which have electrostatic and hydrogen-bond interactions with Lys88, Lys100 and Arg102 in the binding site. PMID- 26857033 TI - Ileal digestibility of nutrients and amino acids in low quality soybean meal sources treated with beta-mannanase for growing pigs. AB - Apparent ileal digestibility (AID) of energy, dry matter (DM), nitrogen (N) and amino acids and standardized ileal digestibility (SID) of amino acids in low quality soybean meals with different CP concentration (SBM 44% CP and SBM 48% CP) with or without 400 U beta-mannanase/kg supplementation were evaluated in 20 cannulated barrows ((Landrace*Yorkshire)*Duroc) with an average BW of 25.08+/ 3.42 kg. A N-free diet was used to determine basal endogenous losses of amino acids. The supplementation of beta-mannanase improved (P0.05) AID of N and energy. The type of SBM (SBM 44% CP v. SBM 48% CP) had no effect on AID of DM, N and energy. beta-mannanase improved (P<0.05) AID of sum of essential amino acids, arginine, histidine, lysine, valine and glycine. The SID of lysine was higher (P<0.05) in enzyme supplemented than in non-supplemented diets. Larger AID and SID of threonine and proline (P<0.05) were observed in SBM 48% CP than in SBM 44% CP. In conclusion, the supplementation of enzyme improved AID of arginine, histidine, lysine, valine and glycine, but it did not cause marked difference in SID of these amino acids except for lysine. The low nutrient digestibility of the SBM sources used in the present experiment might have favoured the positive effect of beta-mannanase supplementation. PMID- 26857032 TI - Dietary management of heart failure: room for improvement? AB - There is growing awareness of the role of diet in both health and disease management. Much data are available on the cardioprotective diet in the primary and secondary prevention of CVD. However, there is limited information on the role of diet in the management of heart failure (HF). Animal models of HF have provided interesting insight and potential mechanisms by which dietary manipulation may improve cardiac performance and delay the progression of the disease, and small-scale human studies have highlighted beneficial diet patterns. The aim of this review is to summarise the current data available on the role of diet in the management of human HF and to demonstrate that dietary manipulation needs to progress further than the simple recommendation of salt and fluid restriction. PMID- 26857035 TI - Insight into the crystallization of amorphous imine-linked polymer networks to 2D covalent organic frameworks. AB - We explore the crystallization of a high surface area imine-linked two dimensional covalent organic framework (2D COF). The growth process reveals rapid initial formation of an amorphous network that subsequently crystallizes into the layered 2D network. The metastable amorphous polymer may be isolated and resubjected to growth conditions to form the COF. These experiments provide the first mechanistic insight into the mechanism of imine-linked 2D COF formation, which is distinct from that of boronate-ester linked COFs. PMID- 26857034 TI - Tunable electromagnetically induced transparency in coupled three-dimensional split-ring-resonator metamaterials. AB - Metamaterials have recently enabled coupling induced transparency due to interference effects in coupled subwavelength resonators. In this work, we present a three dimensional (3-D) metamaterial design with six-fold rotational symmetry that shows electromagnetically induced transparency with a strong polarization dependence to the incident electromagnetic wave due to the ultra sharp resonance line width as a result of interaction between the constituent meta-atoms. However, when the six-fold rotationally symmetric unit cell design was re-arranged into a fourfold rotational symmetry, we observed the excitation of a polarization insensitive dual-band transparency. Thus, the 3-D split-ring resonators allow new schemes to observe single and multi-band classical analogues of electromagnetically induced transparencies that has huge potential applications in slowing down light, sensing modalities, and filtering functionalities either in the passive mode or the active mode where such effects could be tuned by integrating materials with dynamic properties. PMID- 26857036 TI - Mental disorder diagnoses of offspring affected by parental cancer before early adulthood: the 1987 Finnish Birth Cohort study. AB - OBJECTIVE: The purpose of this study is to investigate psychiatric diagnoses given to children affected by parental cancer in psychiatric and somatic specialized health care settings. METHODS: The 1987 Finnish Birth Cohort data (n = 59 476) were followed up through national registers from birth of cohort members up to the end of 2008. The health-related data of cohort members and their parents were obtained from the Care Register of Health Care provided by the National Institute of Health and Wellbeing. RESULTS: By the age of 21 years 7711 of the cohort members had used specialized psychiatric outpatient care and, of them, 549 (7.1%) were affected by parental cancer. Of affected offspring a mental disorder diagnosis was made in 424 (77.2%), while 125 (22.8%) children had not been given any specific mental disorder diagnosis. In females the likelihood for a mental disorder diagnosis assessed in outpatient care was significantly increased by up to 1.2 fold in cases of parental cancer. In males with a father having cancer, psychological development disorders were significantly increased whether assessed in outpatient (OR 1.5) or inpatient (OR1.9) settings. CONCLUSIONS: The prevalence of psychiatric diagnoses in children with parental cancer does not seem to differ from those of children with parents without cancer. However, evidence was found that children affected by parental cancer are at increased risk for some specific psychiatric disorders. Quarter of affected offspring who were referred to specialized psychiatric outpatient care only received diagnoses related to use of health care services or crises or received no psychiatric diagnosis at all. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26857038 TI - A Case Study of the High-speed Train Crash Outside Santiago de Compostela, Galicia, Spain. AB - INTRODUCTION: The worldwide use of rail transport has increased, and the train speeds are escalating. Concurrently, the number of train disasters has been amplified globally. Consequently, railway safety has become an important issue for the future. High-velocity crashes increase the risk for injuries and mortality; nevertheless, there are relatively few studies on high-speed train crashes and the influencing factors on travelers' injuries occurring in the crash phase. The aim of this study was to investigate the fatal and non-fatal injuries and the main interacting factors that contributed to the injury process in the crash phase of the 2013 high-velocity train crash that occurred at Angrois, outside Santiago de Compostela, Spain. METHODS: Hospital records (n=157) of all the injured who were admitted to the six hospitals in the region were reviewed and compiled by descriptive statistics. The instant fatalities (n=63) were collected on site. Influencing crash factors were observed on the crash site, by carriage inspections, and by reviewing official reports concerning the approximated train speed. RESULTS: The main interacting factors that contributed in the injury process in the crash phase were, among other things, the train speed, the design of the concrete structure of the curve, the robustness of the carriage exterior, and the interior environment of the carriages. Of the 222 people on board (218 passengers and four crew), 99% (n=220) were fatally or non fatally injured in the crash. Thirty-three percent (n=72) suffered fatal injuries, of which 88% (n=63) died at the crash site and 13% (n=9) at the hospital. Twenty-one percent (n=32) of those admitted to hospital suffered multi trauma (ie, extensive, severe, and/or critical injuries). The head, face, and neck sustained 42% (n=123) of the injuries followed by the trunk (chest, abdomen, and pelvis; n=92; 32%). Fractures were the most frequent (n=200; 69%) injury. CONCLUSION: A mass-casualty incident with an extensive amount of fatal, severe, and critical injuries is most probable with a high-velocity train; this presents prehospital challenges. This finding draws attention to the importance of more robust carriage exteriors and injury minimizing designs of both railway carriages and the surrounding environment to reduce injuries and fatalities in future high speed crashes. PMID- 26857037 TI - Inhibitory effect of cadmium on estrogen signaling in zebrafish brain and protection by zinc. AB - The present study was conducted to assess the effects of Cd exposure on estrogen signaling in the zebrafish brain, as well as the potential protective role of Zn against Cd-induced toxicity. For this purpose, the effects on transcriptional activation of the estrogen receptors (ERs), aromatase B (Aro-B) protein expression and molecular expression of related genes were examined in vivo using wild-type and transgenic zebrafish embryos. For in vitro studies, an ER-negative glial cell line (U251MG) transfected with different zebrafish ER subtypes (ERalpha, ERbeta1 and ERbeta2) was also used. Embryos were exposed either to estradiol (E2 ), Cd, E2 +Cd or E2 +Cd+Zn for 72 h and cells were exposed to the same treatments for 30 h. Our results show that E2 treatment promoted the transcriptional activation of ERs and increased Aro-B expression, at both the protein and mRNA levels. Although exposure to Cd, does not affect the studied parameters when administered alone, it significantly abolished the E2 -stimulated transcriptional response of the reporter gene for the three ER subtypes in U251 MG cells, and clearly inhibited the E2 induction of Aro-B in radial glial cells of zebrafish embryos. These inhibitory effects were accompanied by a significant downregulation of the expression of esr1, esr2a, esr2b and cyp19a1b genes compared to the E2 -treated group used as a positive control. Zn administration during simultaneous exposure to E2 and Cd strongly stimulated zebrafish ERs transactivation and increased Aro-B protein expression, whereas mRNA levels of the three ERs as well as the cyp19a1b remained unchanged in comparison with Cd treated embryos. In conclusion, our results clearly demonstrate that Cd acts as a potent anti-estrogen in vivo and in vitro, and that Cd-induced E2 antagonism can be reversed, at the protein level, by Zn supplement. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26857039 TI - Full 3-dimensional digital workflow for multicomponent dental appliances: A proof of concept. AB - BACKGROUND: The authors used a 3-dimensional (3D) printer and a bending robot to produce a multicomponent dental appliance to assess whether 3D digital models of the dentition are applicable for a full digital workflow. METHODS: The authors scanned a volunteer's dentition with an intraoral scanner (Lava Chairside Oral Scanner C.O.S., 3M). A digital impression was used to design 2 multicomponent orthodontic appliances. Biocompatible acrylic baseplates were produced with the aid of a 3D printer. The metal springs and clasps were produced by a bending robot. The fit of the 2 appliances was assessed by 2 experienced orthodontists. RESULTS: The authors assessed both orthodontic appliances with the volunteer's dentition and found the fit to be excellent. CONCLUSIONS: Clinicians can fully produce a multicomponent dental appliance consisting of both an acrylic baseplate and other parts, such as clasps, springs, or screws, using a digital workflow process without the need for a physical model of the patient's dentition. PRACTICAL IMPLICATIONS: Plaster models can be superfluous for orthodontic treatment as digital models can be used in all phases of a full digital workflow in orthodontics. The arduous task of making a multicomponent dental appliance that involves bending wires can possibly be replaced by a computer, design software, a 3D printer, and a bending robot. PMID- 26857040 TI - Tobacco dependence education: A survey of US and Canadian dental schools. AB - BACKGROUND: Tobacco use is the leading preventable cause of morbidity and premature mortality and is a significant factor in the development of oral disease. Tobacco dependence education (TDE) has not, however, been consistently integrated into predoctoral education. The authors conducted a study assessing the content and extent of TDE and intervention skills in US and Canadian dental schools. METHODS: In 2013, the authors contacted the academic deans of the 74 accredited US and Canadian dental schools to identify the educator who would be most appropriately described as the tobacco-use cessation "champion" at their institution. The authors e-mailed an introductory letter to each school's champion with a hyperlink to a 45-item survey; 2 follow-up emails were sent with links to the survey. RESULTS: The response rate was 66% (N = 49). TDE was taught at 92% of dental schools; 90% of respondents indicated that faculty members were confident to extremely confident in teaching tobacco-related pathology. Only 49% reported this level of confidence in teaching students how to help patients quit tobacco. TDE is taught in periodontics (82%), oral pathology (77%), clinic (66%), oral diagnosis (59%), public health dentistry (55%), pharmacology (55%), oral medicine (52%), and other disciplines (less than 50%). CONCLUSIONS: The survey responses revealed that TDE is not a curricular component in all US and Canadian dental schools. Faculty members were most confident in teaching tobacco-related pathology but may lack the interest and skills needed to integrate TDE as part of patient care. PRACTICE IMPLICATIONS: Patients who use tobacco in any form are at an increased risk of developing periodontitis, developing oral cancer, and having poorer surgical outcomes, emphasizing the need for the dental team to be well prepared through predoctoral dental education. PMID- 26857041 TI - Antibiotic prescribing by dentists has increased: Why? AB - BACKGROUND: Although the overall rate of antibiotic prescribing has been declining in British Columbia, Canada, the authors conducted a study to explain the increased rate of prescribing by dentists. METHODS: The authors obtained anonymized, line-listed data on outpatient prescriptions from 1996 to 2013 from a centralized, population-based prescription database, including a variable coding prescriber licensing body. Analyses used Anatomical Therapeutic Classification standard codes and defined daily dose (DDD) values. The authors normalized prescribing rates to the population and expressed the rates in DDDs per 1,000 inhabitants per day (DID). The Canadian Dental Association released a webinar that invited correspondence from dentists about the drivers of the trend. RESULTS: From 1996 to 2013, overall antibiotic use declined from 18.24 DID to 15.91 DID, and physician prescribing declined 18.2%, from 17.25 DID to 14.11 DID. However, dental prescribing increased 62.2%, from 0.98 DID to 1.59 DID, and its proportionate contribution increased from 6.7% to 11.3% of antibiotic prescriptions. The rate of prescribing increased the most for dental patients 60 years or older. Communication from dentists in Canada and the United States identified the following explanatory themes: unnecessary prescriptions for periapical abscess and irreversible pulpitis; increased prescribing associated with dental implants and their complications; slow adoption of guidelines calling for less perioperative antibiotic coverage for patients with valvular heart disease and prosthetic joints; emphasis on cosmetic practices reducing the surgical skill set of average dentists; underinsurance practices driving antibiotics to be a substitute for surgery; the aging population; and more dental registrants per capita. CONCLUSIONS: Emerging themes for dental prescribing should be explored further in future studies; however, themes already identified may guide priorities in antibiotic stewardship for continuing dental education sessions. PRACTICAL IMPLICATIONS: Antibiotic prescribing should be reviewed to make sure that we are compliant with guidelines. Most practitioners will find opportunities to prescribe less often and for shorter durations. PMID- 26857042 TI - Comments on the "Effects of in utero exposure to polychlorinated biphenyls, methylmercury, and polyunsaturated fatty acids on birth size". PMID- 26857043 TI - [Relevance of first trimester serum markers to predict pregnancy complications: A Tunisian preliminary study]. AB - OBJECTIVES: Identify applications and utility of serum markers dosed in the first trimester in predicting, early diagnosis and management of various complications of pregnancy. METHODS: Eight hundred and eighty patients were included in this prospective regional study performed in the governorate of Bizerte in northern Tunisia in collaboration between the private and public sectors. Serum markers of the first quarter, PAPP A and betahCG, were measured in the same laboratory. The performance of these markers was studied in the prediction of adverse pregnancy complications. RESULTS: The prevalence of various pregnancy complications was 8.6% for birth prematurely, 9.2% for hypertension or preeclampsia, IUGR 5.8% and 7.3% for loss pregnancy. PAPP A levels were lower in fetal loss group (P=0.005), vascular disease group (P=0.001) and preterm delivery group (P=0.001). In addition, a lower rate of betahCG was associated with the occurrence of placental pathologies such as growth retardation (P=0.037) and hypertension (P=0.034) and appears to have no predictive value in the occurrence of preterm birth (P=0.76) and fetal loss (P=0.189). Logistic regression analysis showed a significant predictive value of these markers. CONCLUSION: Serum markers of the first trimester appear to have adequate predictive validity of adverse pregnancy complications. A risk predictive model could be designed based on these markers and involving maternal and ultrasound features in order to target prophylactically a high risk population. PMID- 26857044 TI - [Pelvic actinomycosis: Diagnostic and therapeutic aspects]. AB - OBJECTIVES: Actinomycosis is a rare little known granulomatous suppurative disease, more common in women, aided by the use of contraceptive purposes intrauterine device (IUD). Pelvic location is the rarest with an extension to adjacent organs making preoperative diagnosis difficult and misleading clinical presentation. Early diagnosis of this affection determines the therapeutic strategy and avoids mutilating interventions especially in young women. METHODS: We reviewed the record of women who consulted the department of obstetrics and gynecology at Ben Arous hospital (Tunisia) between January 2003 and December 2013 for a pelvic pain syndrome and in whom diagnosis of actinomycosis was suspected by clinical and imaging and confirmed by pathology. RESULTS: Eight cases of gynecologic abdominopelvic actinomycosis were diagnosed during the study period. Seven patients were carriers of an intrauterine device, with an average duration of 5 years wearing. Functional signs were essentially pelvic pain and fever. Physical examination of patients mainly showed two clinical presentations: a pelvic tumor syndrome or abdominopelvic and an array of pelvic abscess or pelvic inflammatory disease. Radiological investigations were allowed to suspect the diagnosis of actinomycosis only in one patient, in whom percutaneous biopsy confirmed the histological diagnosis without resorting to a surgical procedure. Operative procedures performed were varied as appropriate. The diagnosis of actinomycosis was made by pathology without any cases of bacterial isolation. All patients received antibiotic treatment with penicillin. The subsequent evolution was favorable. CONCLUSION: The diagnosis of actinomycosis should be considered in any invasive abdominal mass of neoplastic appearance and in case of table of genital infection especially in patients bearing IUD for 5 years or more. PMID- 26857045 TI - [Instrumental delivery with perineum-fetal head distance >55 MM on ultrasound]. AB - OBJECTIVE: Compare the issue of an operative vaginal delivery associated to the fetal presentation diagnosed by transperineal ultrasound. Three groups were formed: >=55 mm, between 45 and 55 mm, and <45 mm. METHODS: A monocentric prospective study on 108 patients has been conducted between April 2011 and August 2014. The distance between perinea and skull has been analyzed to compare the success of operative vaginal delivery considering the level of the fetal presentation in the pelvic cavity. RESULTS: The failed operative vaginal deliveries are more frequent while the fetal head is above 55 mm (16.7%) or while the fetal head is between 45 and 55 mm (9.1%) than while the fetal skull is under 45 mm (1.8%) (P=0.04). However there is no significant difference for the fetal shoulder dystocia (5.6% vs 3.0% vs 3.5%, P=0.5), nor for the newborn outcomes (16.7 vs 15.2 vs 14; P=0.9). CONCLUSION: Despite the high rate of failed operative vaginal delivery above 55 mm, it should be considered not to prohibit but send free to the obstetrician appreciation. PMID- 26857046 TI - [Cutaneous manifestation of stonefish sting in French Polynesia]. PMID- 26857047 TI - Truth or Consequences. PMID- 26857048 TI - Infant Scoring: The Force Awakens. PMID- 26857049 TI - Explaining the Relation between Nightmares and Suicide. PMID- 26857050 TI - Lowest Oxyhemoglobin Saturation May Be an Independent Factor Influencing Auditory Function in Severe Obstructive Sleep Apnea. AB - STUDY OBJECTIVES: The aims of this study were to determine if a correlation exists between the level of hypoxia induced by severe obstructive sleep apnea syndrome (OSAS) and the level of auditory dysfunction when verifying such a relationship using polysomnography (PSG). METHODS: A retrospective review of 41 patients with severe OSAS was performed. Independent risk factors for hearing impairment included parameters of PSG, which were analyzed in two hearing groups at a level >= 40 decibels (dB). RESULTS: Oxyhemoglobin saturation, especially the lowest oxyhemoglobin saturation level, showed lower thresholds in the hearing impairment group than in the control group (p = 0.039 at NREM stage; p = 0.029 at REM stage; p = 0.001 at total sleep stage). After adjusting for other risk factors, the sole variable that remained significant was lowest oxyhemoglobin saturation (total; p = 0.046). In the correlation analysis, a decreasing lowest oxyhemoglobin saturation (from all subjects, n = 41) correlated with a greater mean hearing threshold (R(2) = 0.297; p < 0.001). CONCLUSION: Our results indicated that lowest oxyhemoglobin saturation in PSG is the only variable correlated with the hearing threshold. This finding could be predictive of possible hearing alternation in patients with severe OSAS. COMMENTARY: A commentary on this article appears in this issue on page 641. PMID- 26857051 TI - Sleep Apnea Evaluation of Commercial Motor Vehicle Operators. PMID- 26857052 TI - Predicting CPAP Use and Treatment Outcomes Using Composite Indices of Sleep Apnea Severity. AB - STUDY OBJECTIVES: Measures of baseline sleep apnea disease burden (apnea-hypopnea index, Epworth Sleepiness Scale) predict continuous positive airway pressure (CPAP) adherence, but composite indices of sleep apnea severity (Sleep Apnea Severity Index, Modified Sleep Apnea Severity Index) may be more robust measures of disease burden. We tested the relative prognostic ability of each measure of sleep apnea disease burden to predict subsequent CPAP adherence and subjective sleep outcomes. METHODS: Prospective cohort study at a tertiary academic sleep center. Patients (n = 323) underwent initial diagnostic polysomnography for suspected obstructive sleep apnea and 6 mo of subsequent CPAP therapy. RESULTS: Baseline apnea-hypopnea index and both composite indices predicted adherence to CPAP therapy at 6 mo in multivariate analyses (all p <= 0.001). Baseline Epworth Sleepiness Scale did not predict CPAP adherence (p = 0.22). Both composite indices were statistically stronger predictors of CPAP adherence at 6 mo than apnea-hypopnea index (p < 0.001). In multivariate analyses, baseline apnea hypopnea index (p < 0.05) and both composite indices (both p < 0.04) predicted change in Pittsburgh Sleep Quality Index, whereas only the composite indices predicted changes in Sleep Apnea Quality of Life Index (both p < 0.001). Adjustment for treatment adherence did not affect the relationship of the composite indices with change in Sleep Apnea Quality of Life Index (both p <= 0.005). CONCLUSIONS: Composite indices of baseline sleep apnea severity better predict objective CPAP adherence and subjective treatment outcomes than baseline apnea-hypopnea index and baseline Epworth Sleepiness Scale. PMID- 26857054 TI - Psychometric Comparison of the Full and Abbreviated Versions of the Dysfunctional Beliefs and Attitudes about Sleep Scale. AB - STUDY OBJECTIVES: The different versions of the Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS) have limited comparison and summary of the findings across studies. We aimed to examine which version and which subscales had better psychometric properties. METHODS: Data were derived from a randomized controlled trial of internet-based cognitive-behavioral therapy for insomnia (CBT I) vs. waitlist in 312 participants with self-report diagnosis of insomnia disorder. The response distribution, internal consistency, construct and concurrent validity, and sensitivity to change were analyzed. RESULTS: Floor or ceiling effects were found in 19 of the 30 DBAS items. Item-total correlation was < 0.30 in 43.3%, 31.3%, and 10.0% of the items in DBAS-30, DBAS-16, DBAS-10. Internal consistency was satisfactory for total scores, with Cronbach alpha ranging from 0.73-0.81, but 2 subscales of DBAS-30 and 1 subscale of DBAS-10 had Cronbach alpha < 0.35. Factor analysis produced 8, 4, and 3 factors for DBAS-30, DBAS-16, and DBAS-10. Only the factor structure of DBAS-16 was compatible with previous studies. Concurrent validity with insomnia, anxiety, and depressive symptoms was much stronger than with sleep diary parameters. Sensitivities to change of the DBAS scores following CBT-I and with sleep improvement were found, except the DBAS-30 "attributions" subscale and DBAS-16 "medication" subscale. CONCLUSIONS: The DBAS-16 possesses better internal consistency, a reproducible factor structure, strong concurrent validity, and sensitivity to change, and therefore is recommended for research use. The DBAS-30 and DBAS-10 have their own strengths, but there are limitations in their application as a quantitative measure in research. PMID- 26857053 TI - An Open-Labeled Trial of Ramelteon in Idiopathic Rapid Eye Movement Sleep Behavior Disorder. AB - STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by REM sleep without atonia and elaborate motor activity in association with dream mentation. The melatonin receptor agonist ramelteon has been documented as being effective in two patients with secondary RBD. However, there are no reports on ramelteon treatment for idiopathic RBD. METHODS: In an open-labeled trial, we treated 12 consecutive patients with idiopathic RBD for at least 4 w with 8 mg ramelteon given within 30 min before bedtime. RESULTS: Ramelteon treatment did not have a clear effect on REM sleep without atonia or an RBD severity scale measured by video-supported polysomnography. However, clinical assessment using a visual analog scale showed a trend toward significance and there were also definitely positive changes in some individual cases. Ramelteon was well tolerated in most patients, with minor side effects. CONCLUSIONS: Considering that ramelteon is associated with few side effects, further study may ascertain whether patients with RBD could be effectively treated by ramelteon, especially when clonazepam may not be suitable due to its side effects. COMMENTARY: A commentary on this article appears in this issue on page 643. PMID- 26857055 TI - Psychometric Evaluation of the Ford Insomnia Response to Stress Test (FIRST) in Early Pregnancy. AB - STUDY OBJECTIVES: To evaluate the construct validity and factor structure of the Spanish-language version of the Ford Insomnia Response to Stress Test questionnaire (FIRST-S) when used in early pregnancy. METHODS: A cohort of 647 women were interviewed at <= 16 weeks of gestation to collect information regarding lifestyle, demographic, and sleep characteristics. The factorial structure of the FIRST-S was tested through exploratory and confirmatory factor analyses (EFA and CFA). Internal consistency and construct validity were also assessed by evaluating the association between the FIRST-S with symptoms of depression, anxiety, and sleep quality. Item response theory (IRT) analyses were conducted to complement classical test theory (CTT) analytic approaches. RESULTS: The mean score of the FIRST-S was 13.8 (range: 9-33). The results of the EFA showed that the FIRST-S contained a one-factor solution that accounted for 69.8% of the variance. The FIRST-S items showed good internal consistency (Cronbach alpha = 0.81). CFA results corroborated the one-factor structure finding from the EFA; and yielded measures indicating goodness of fit (comparative fit index of 0.902) and accuracy (root mean square error of approximation of 0.057). The FIRST S had good construct validity as demonstrated by statistically significant associations of FIRST-S scores with sleep quality, antepartum depression and anxiety symptoms. Finally, results from IRT analyses suggested excellent item infit and outfit measures. CONCLUSIONS: The FIRST-S was found to have good construct validity and internal consistency for assessing vulnerability to insomnia during early pregnancy. PMID- 26857056 TI - Does Postural Rigidity Decrease during REM Sleep without Atonia in Parkinson Disease? AB - STUDY OBJECTIVES: Rigidity is a muscle hypertonia typical of Parkinson disease (PD), whereas rapid eye movement (REM) sleep behavior disorder (RBD) is characterized by abnormally increased muscle tone during REM sleep (REM sleep without atonia) and enacting dream behaviors. Because movements are not bradykinetic during RBD in patients with PD, we investigated whether the background, wake postural rigidity is attenuated during REM sleep without atonia, in absence of movement. METHODS: The amplitude of levator menti (postural muscle) electromyographic activity during relaxed evening wakefulness (considered as reference) and sleep (N2, N3, atonic REM sleep, and quiet REM sleep without atonia) was measured in 20 patients with PD (with and without RBD), 10 patients with idiopathic RBD patients and 10 healthy subjects. RESULTS: The chin tone amplitude progressively decreased from wake to N2, N3, and atonic REM sleep in the four groups, but the highest amplitude was observed in PD patients with RBD during atonic REM sleep. Furthermore, chin muscle tone amplitude did not attenuate from wake to REM sleep without atonia in patients with both PD and RBD but dramatically attenuated (by 40% on average) in patients with idiopathic RBD. CONCLUSIONS: The high amplitude of chin muscle tone in PD with RBD (but not in idiopathic RBD) during REM sleep with and without atonia suggests that both PD related hypertonia and RBD-related enhanced muscle tone coexist during REM sleep, together affecting chin muscle tone. Consequently, some rapid RBD movements likely start against a rigid postural tone. PMID- 26857057 TI - Sleep/Wake Patterns and Parental Perceptions of Sleep in Children Born Preterm. AB - STUDY OBJECTIVES: To compare sleep/wake patterns in children born preterm in Australia vs Canada and determine cultural differences in the relationship between parental perception of sleep and actual sleep behaviors. METHODS: Australian and Canadian children born preterm were recruited from the Caffeine for Apnea of Prematurity trial (n = 188, 5-12 y) and underwent 14 days actigraphy monitoring. Parents completed the National Sleep Foundation 2004 Sleep in America questionnaire. Cross-cultural differences in sleep characteristics assessed by actigraphy and parent-reported questionnaire were examined. Correlational analyses determined the associations between parental perceptions of child sleep need and sleep behavior. RESULTS: Actigraphy showed preterm children obtained, on average, 8 h sleep/night, one hour less than population recommendations for their age. There was no difference in total sleep time (TST) between Australian and Canadian cohorts; however, bed and wake times were earlier in Australian children. Bedtimes and TST varied by 60 minutes from night to night in both cohorts. Parent-reported child TST on the National Sleep Foundation questionnaire was 90 minutes longer than recorded by actigraphy. Both bedtime and TST on weekdays and weekends were related to parental perception of child sleep need in the Australian cohort. Only TST on weekdays was related to parental perception of child sleep need in the Canadian cohort. CONCLUSIONS: This study suggests that short sleep duration and irregular sleep schedules are common in children born preterm. Cultural differences in the association between parental perception of child sleep need and actual sleep behaviors provide important targets for future sleep health education. PMID- 26857058 TI - Comparison of Sleep Problems in Individuals with Spinal Cord Injury and Multiple Sclerosis. AB - STUDY OBJECTIVES: Sleep problems are common in spinal cord injury (SCI) and multiple sclerosis (MS). However, the degree to which sleep problems differ between these distinct clinical populations has not been evaluated. In this study, we examined self-reported sleep problems in individuals with SCI and those with MS, and compared these clinical groups on the Medical Outcomes Study Sleep Scale (MOS-SS). METHODS: Participants were 1,677 individuals (SCI = 581; MS = 1,096) enrolled in longitudinal study of self-reported health outcomes in SCI and MS. Univariate and multivariate analysis of covariance examined group differences on global sleep problems and domain-specific subscales of the MOS-SS. RESULTS: Individuals with SCI reported an average of 30 fewer min of sleep per night (Sleep Quantity subscale) and significantly greater difficulty initiating and maintaining sleep (Sleep Disturbance subscale) compared to individuals with MS. However, groups did not differ on global sleep problems (Sleep Problems Index 9). CONCLUSIONS: Although global sleep problems are more common in SCI and MS than in the general population, these groups exhibit differing sleep problem profiles, and thus may require unique treatment approaches to address the specific domains of sleep affected. For individuals with SCI, an additional focus on increasing sleep quantity and reducing sleep disruptions may be warranted. PMID- 26857059 TI - Short-Term Variability in Apnea-Hypopnea Index during Extended Home Portable Monitoring. AB - STUDY OBJECTIVES: Apnea-hypopnea index (AHI) is the primary measure used to confirm a diagnosis of obstructive sleep apnea (OSA). However, there may be significant night-to-night variability (NNV) in AHI, limiting the value of AHI in clinical decision-making related to OSA management. We examined short-term NNV in AHI and its predictors during home portable monitoring (PM). METHODS: Single center prospective observational study of patients (n = 84) with newly diagnosed OSA by polysomnography (PSG) AHI >= 5/h. All participants underwent 2 to 8 consecutive nights of PM. RESULTS: Participants (n = 84) were middle-aged (47 +/- 8.3 y, mean +/- standard deviation; SD), including 28 women, with mean AHI on baseline PSG (AHIPSG) of 30.1 +/- 31.8. Mean AHI on PM (AHIPM) was 27.4 +/- 23.7. Intraclass correlation coefficient (ICC) for AHIPM in the entire sample was 0.73 (95% CI 0.66-0.8), indicating that 27% of the variability in AHIPM was due to intra-individual factors. Mild severity of OSA, defined by AHIPSG 5-15/h, was associated with higher NNV (likelihood ratio, -0.4 +/- 0.14; p = 0.006) and absence of comorbidity showed a trend towards higher NNV (-0.54 +/- 0.27, p = 0.05) on AHIPM. CONCLUSIONS: The intraindividual short-term NNV in AHIPM is higher in mild versus moderately severe OSA, even in the home setting, where first-night effect is not expected. Larger studies of NNV focused on patients with mild OSA are needed to identify characteristics that predict need and timing for repeated diagnostic testing and treatment. COMMENTARY: A commentary on this article appears in this issue on page 787. PMID- 26857061 TI - Perfect Periodicity: To Be Or Not To Be Periodic Leg Movements. PMID- 26857060 TI - Is Insomnia Lonely? Exploring Thwarted Belongingness as an Explanatory Link between Insomnia and Suicidal Ideation in a Sample of South Korean University Students. AB - STUDY OBJECTIVES: Suicide is a serious public health problem, and suicide rates are particularly high in South Korea. Insomnia has been identified as a risk factor for suicidal ideation; however, little is known about the mechanisms accounting for this relationship in this population. Based on the premise that insomnia can be lonely (e.g., being awake when everyone else is asleep), the purpose of this study was to examine whether greater insomnia severity would be associated with higher levels of thwarted belongingness and suicidal ideation, and whether thwarted belongingness would mediate the relationship between insomnia and suicidal ideation. METHODS: Predictions were tested in a sample of 552 South Korean young adults who completed self-report measures of insomnia severity, suicidal ideation, and thwarted belongingness. RESULTS: Greater insomnia symptom severity was significantly and positively associated with thwarted belongingness and suicidal ideation. Mediation analyses revealed that thwarted belongingness significantly accounted for the relationship between insomnia severity and suicidal ideation. CONCLUSIONS: These findings highlight the potential importance of monitoring and therapeutically impacting insomnia and thwarted belongingness to help reduce suicide risk. PMID- 26857062 TI - pH-dependent cytotoxic effects of extracts of the marine sponge Polymastia janeirensis on cancer cell lines. AB - The purpose of this work was to study the cytotoxic effects of marine sponge Polymastia janeirensis, which has been observed in the field to release an orange substance that is toxic to fish. The result showed that aqueous extract (pH 7.0) was highly cytotoxic to glioma (U87) and neuroblastoma (SHSY5Y) cancer cell lines (IC50 < 1.0 MUg/mL). In addition, this extract showed potent antioxidant and procoagulant (decreased the clotting time by 1.7-fold) activities. Interestingly, the cytotoxic effects were pH-dependent since the viability of the cancer cells was not affected with the extract (pH 5.5). The close similarity between the aqueous extract (pH 7.0) and the orange liquid that is released by the sponge indicates that this potential chemical defence of P. janeirensis deserves further investigation. PMID- 26857063 TI - A Suggested Molecular Pathology Curriculum for Residents: A Report of the Association for Molecular Pathology. AB - Molecular pathology is an essential element of pathology training. As more molecular tests have become available, there is an increasing need for pathology trainees to receive a strong foundation in molecular pathology. Appointed by the Training and Education Committee of the Association for Molecular Pathology, the Molecular Curriculum Task Force has developed a suggested curriculum in molecular pathology for residents. The foundations of molecular pathology are presented as a series of goals and objectives that residency programs can use to develop their educational programs. As pathologists continue to expand their roles to include regular clinical consultations in the realm of molecular testing, a strong foundation in molecular pathology and genomic medicine has become essential to the practice of pathology. PMID- 26857064 TI - Robust Detection of DNA Hypermethylation of ZNF154 as a Pan-Cancer Locus with in Silico Modeling for Blood-Based Diagnostic Development. AB - Sites that display recurrent, aberrant DNA methylation in cancer represent potential biomarkers for screening and diagnostics. Previously, we identified hypermethylation at the ZNF154 CpG island in 15 solid epithelial tumor types from 13 different organs. In this study, we measure the magnitude and pattern of differential methylation of this region across colon, lung, breast, stomach, and endometrial tumor samples using next-generation bisulfite amplicon sequencing. We found that all tumor types and subtypes are hypermethylated at this locus compared with normal tissue. To evaluate this site as a possible pan-cancer marker, we compare the ability of several sequence analysis methods to distinguish the five tumor types (184 tumor samples) from normal tissue samples (n = 34). The classification performance for the strongest method, measured by the area under (the receiver operating characteristic) curve (AUC), is 0.96, close to a perfect value of 1. Furthermore, in a computational simulation of circulating tumor DNA, we were able to detect limited amounts of tumor DNA diluted with normal DNA: 1% tumor DNA in 99% normal DNA yields AUCs of up to 0.79. Our findings suggest that hypermethylation of the ZNF154 CpG island is a relevant biomarker for identifying solid tumor DNA and may have utility as a generalizable biomarker for circulating tumor DNA. PMID- 26857065 TI - Next-Generation Sequencing-Assisted DNA-Based Digital PCR for a Personalized Approach to the Detection and Quantification of Residual Disease in Chronic Myeloid Leukemia Patients. AB - Recent studies indicate that 40% of chronic myeloid leukemia patients who achieve sustained undetectable BCR-ABL1 transcripts on tyrosine kinase inhibitor therapy remain disease-free after drug discontinuation. In contrast, 60% experience return of detectable disease and have to restart treatment, thus highlighting the need for an improved method of identifying patients with the lowest likelihood of relapse. Here we describe the validation of a personalized DNA-based digital PCR (dPCR) approach for quantifying very low levels of residual disease, which involves the rapid identification of t(9;22) fusion junctions using targeted next generation sequencing coupled with the use of a dPCR platform. t(9;22) genomic breakpoints were successfully mapped in samples from 32 of 32 patients with early stage disease. Disease quantification by DNA-based dPCR was performed using the Fluidigm BioMark platform on 46 follow-up samples from 6 of the 32 patients, including 36 samples that were in deep molecular remission. dPCR detected persistent disease in 81% of molecular-remission samples, outperforming both RT dPCR (25%) and DNA-based quantitative PCR (19%). We conclude that dPCR for BCR ABL1 DNA is the most sensitive available method of residual-disease detection in chronic myeloid leukemia and may prove useful in the management of tyrosine kinase inhibitor withdrawal. PMID- 26857066 TI - Durable Benefits of Cellular Postconditioning: Long-Term Effects of Allogeneic Cardiosphere-Derived Cells Infused After Reperfusion in Pigs with Acute Myocardial Infarction. AB - BACKGROUND: Infusion of allogeneic cardiosphere-derived cells (allo-CDCs) postreperfusion elicits cardioprotective cellular postconditioning in pigs with acute myocardial infarction. However, the long-term effects of allo-CDCs have not been assessed. We performed a placebo-controlled pivotal study for long-term evaluation, as well as shorter-term mechanistic studies. METHODS AND RESULTS: Minipigs underwent 1.5-hour mid-left anterior descending balloon occlusion followed by reperfusion and were randomized to receive intracoronary allo-CDCs or vehicle 30 minutes postreperfusion. Left ventriculography (LVG) demonstrated preserved ejection fraction (EF) and attenuation of LV remodeling in CDC-treated pigs. Pigs underwent cardiac magnetic resonance imaging (MRI) and LVG 1 hour and 8 weeks after therapy to evaluate efficacy. MRI showed improvement of EF and attenuation of LV remodeling immediately after allo-CDC infusion. In addition, allo-CDCs improved regional function and decreased hypertrophy 2 months post treatment. Histological analysis revealed increased myocardial salvage index, enhanced vascularity, sustained reductions in infarct size/area at risk and scar transmurality, and attenuation of collagen deposition in the infarct zone of allo CDC-treated pigs at 2 months. Allo-CDCs did not evoke lymphohistiocytic infiltration or systemic humoral memory response. Short-term experiments designed to probe mechanism revealed antiapoptotic effects of allo-CDCs on cardiomyocytes and increases in cytoprotective macrophages, but no increase in overall inflammatory cell infiltration 2 hours after cell therapy. CONCLUSIONS: Allo-CDC infusion postreperfusion is safe, improves cardiac function, and attenuates scar size and remodeling. The favorable effects persist for at least 2 months after therapy. Thus, cellular postconditioning confers not only acute cardioprotection, but also lasting structural and functional benefits. PMID- 26857068 TI - gamma-Glutamyltransferase and Risk of Sudden Cardiac Death in Middle-Aged Finnish Men: A New Prospective Cohort Study. AB - BACKGROUND: gamma-Glutamyltransferase (GGT) has been linked to an increased risk of several cardiovascular outcomes; however, the relationship of GGT with sudden cardiac death (SCD) has not been investigated previously. We aimed to assess the association of GGT with risk of SCD. METHODS AND RESULTS: Serum GGT activity was assessed at baseline in the Kuopio Ischemic Heart Disease prospective cohort of 1780 men, and 136 SCDs were recorded during 22 years of follow-up. Correction for within-person variability was made using data from repeated measurements taken several years apart. The regression dilution ratio of loge GGT adjusted for age was 0.68 (95% CI 0.61-0.74). Serum GGT was log-linearly associated with risk of SCD. The hazard ratio for SCD per 1 SD higher baseline loge GGT values (2-fold higher) was 1.30 (95% CI 1.10-1.54; P=0.002) after adjustment for several established risk factors and remained consistent with further adjustment for alcohol consumption, resting heart rate, lipids, and C-reactive protein (hazard ratio 1.26, 95% CI 1.05-1.50; P=0.014). The corresponding hazard ratios were 1.48 (95% CI 1.15-1.89; P=0.002) and 1.40 (95% CI 1.07-1.82; P=0.014) after correction for within-person variability. Hazard ratios remained unchanged after accounting for incident coronary events and did not vary importantly by levels or categories of prespecified conventional risk factors. CONCLUSIONS: GGT is positively, log linearly, and independently associated with future risk of SCD in the general male population. Further research is needed to replicate these findings. PMID- 26857069 TI - Impact of Prosthesis-Patient Mismatch on Left Ventricular Myocardial Mechanics After Transcatheter Aortic Valve Replacement. AB - BACKGROUND: The aim of this study was to compare left ventricular (LV) remodeling using myocardial strain between patients with severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR) with and without prosthesis patient mismatch (PPM). METHODS AND RESULTS: In a retrospective study, speckle tracking echocardiography was used to measure global longitudinal strain (GLS) and strain rate (GLSR), circumferential strain, and rotation before and at mid term follow-up post-TAVR. Moderate and severe PPM were defined as an effective orifice area <=0.85 and <0.65 cm(2)/m(2), respectively. A total of 102 patients (median age, 83 years [77-88]) with severe AS were included. At 6+/-3 months post TAVR, moderate and severe PPM were found in 32 (31%) and 9 (9%) patients. Patients without PPM had a significant regression in LV mass (from 134+/-41 to 119+/-38 g/m(2); P=0.001) at follow-up whereas those with PPM did not. There was a significant improvement in LV GLS (-12.8+/-4.0 to -14.3+/-4.3%; P=0.01), GLSR ( 0.61+/-0.20 to -0.73+/-0.25 second(-1); P<0.001), and early diastolic strain rate (0.52+/-0.20 to 0.64+/-0.20 second(-1); P<0.001) in patients without PPM, but not in those with PPM. After adjustment for pre-TAVR ejection fraction and post-TAVR aortic regurgitation, patients without PPM had greater improvement in LV longitudinal strain parameters compared to those with PPM. After a median follow up of 46.1 months (interquartile range, 35.4-60.8), there was no difference in survival between patients with and without PPM. CONCLUSIONS: TAVR was associated with an incidence of PPM of 40%. Greater reverse LV remodeling using myocardial strain was evident in patients without PPM compared to PPM. Presence of PPM was not associated with mortality. PMID- 26857071 TI - What is the veterinary professional identity? Preliminary findings from web-based continuing professional development in veterinary professionalism. AB - Professionalism and professional skills are increasingly being incorporated into veterinary curricula; however, lack of clarity in defining veterinary professionalism presents a potential challenge for directing course outcomes that are of benefit to the veterinary professional. An online continuing education course in veterinary professionalism was designed to address a deficit in postgraduate support in this area; as part of this course, delegates of varying practice backgrounds participated in online discussions reflecting on the implications of professional skills for their clinical practice. The discussions surrounding the role of the veterinary professional and reflecting on strengths and weaknesses in professional skills were analysed using narrative methodology, which provided an understanding of the defining skills and attributes of the veterinary professional, from the perspectives of those involved (i.e. how vets understood their own career identity). The veterinary surgeon was understood to be an interprofessional team member, who makes clinical decisions in the face of competing stakeholder needs and works in a complex environment comprising multiple and diverse challenges (stress, high emotions, financial issues, work life balance). It was identified that strategies for accepting fallibility, and those necessary for establishing reasonable expectations of professional behaviour and clinical ability, are poorly developed. PMID- 26857067 TI - miR-342-5p Is a Notch Downstream Molecule and Regulates Multiple Angiogenic Pathways Including Notch, Vascular Endothelial Growth Factor and Transforming Growth Factor beta Signaling. AB - BACKGROUND: Endothelial cells (ECs) form blood vessels through angiogenesis that is regulated by coordination of vascular endothelial growth factor (VEGF), Notch, transforming growth factor beta, and other signals, but the detailed molecular mechanisms remain unclear. METHODS AND RESULTS: Small RNA sequencing initially identified miR-342-5p as a novel downstream molecule of Notch signaling in ECs. Reporter assay, quantitative reverse transcription polymerase chain reaction and Western blot analysis indicated that miR-342-5p targeted endoglin and modulated transforming growth factor beta signaling by repressing SMAD1/5 phosphorylation in ECs. Transfection of miR-342-5p inhibited EC proliferation and lumen formation and reduced angiogenesis in vitro and in vivo, as assayed by using a fibrin beads based sprouting assay, mouse aortic ring culture, and intravitreal injection of miR-342-5p agomir in P3 pups. Moreover, miR-342-5p promoted the migration of ECs, accompanied by reduced endothelial markers and increased mesenchymal markers, indicative of increased endothelial-mesenchymal transition. Transfection of endoglin at least partially reversed endothelial-mesenchymal transition induced by miR-342-5p. The expression of miR-342-5p was upregulated by transforming growth factor beta, and inhibition of miR-342-5p attenuated the inhibitory effects of transforming growth factor beta on lumen formation and sprouting by ECs. In addition, VEGF repressed miR-342-5p expression, and transfection of miR 342-5p repressed VEGFR2 and VEGFR3 expression and VEGF-triggered Akt phosphorylation in ECs. miR-342-5p repressed angiogenesis in a laser-induced choroidal neovascularization model in mice, highlighting its clinical potential. CONCLUSIONS: miR-342-5p acts as a multifunctional angiogenic repressor mediating the effects and interaction among angiogenic pathways. PMID- 26857070 TI - Impact of an Emergency Department Observation Unit Management Algorithm for Atrial Fibrillation. AB - BACKGROUND: Atrial fibrillation (AF) is a common, growing, and costly medical condition. We aimed to evaluate the impact of a management algorithm for symptomatic AF that used an emergency department observation unit on hospital admission rates and patient outcomes. METHODS AND RESULTS: This retrospective cohort study compared 563 patients who presented consecutively in the year after implementation of the algorithm, from July 2013 through June 2014 (intervention group), with 627 patients in a historical cohort (preintervention group) who presented consecutively from July 2011 through June 2012. All patients who consented to have their records used for chart review were included if they had a primary final emergency department diagnosis of AF. We observed no significant differences in age, sex, vital signs, body mass index, or CHADS2 (congestive heart failure, hypertension, age, diabetes mellitus, and prior stroke or transient ischemic attack) score between the preintervention and intervention groups. The rate of inpatient admission was significantly lower in the intervention group (from 45% to 36%; P<0.001). The groups were not significantly different with regard to rates of return emergency department visits (19% versus 17%; P=0.48), hospitalization (18% versus 16%; P=0.22), or adverse events (2% versus 2%; P=0.95) within 30 days. Emergency department observation unit admissions were 40% (P<0.001) less costly than inpatient hospital admissions of <=1 day's duration. CONCLUSIONS: Implementation of an emergency department observation unit AF algorithm was associated with significantly decreased hospital admissions without increasing the rates of return emergency department visits, hospitalization, or adverse events within 30 days. PMID- 26857072 TI - Chemical and Biophysical Modulation of Cas9 for Tunable Genome Engineering. AB - The application of the CRISPR-Cas9 system for genome engineering has revolutionized the ability to interrogate genomes of mammalian cells. Programming the Cas9 endonuclease to induce DNA breaks at specified sites is achieved by simply modifying the sequence of its cognate guide RNA. Although Cas9-mediated genome editing has been shown to be highly specific, cleavage events at off target sites have also been reported. Minimizing, and eventually abolishing, unwanted off-target cleavage remains a major goal of the CRISPR-Cas9 technology before its implementation for therapeutic use. Recent efforts have turned to chemical biology and biophysical approaches to engineer inducible genome editing systems for controlling Cas9 activity at the transcriptional and protein levels. Here, we review recent advancements to modulate Cas9-mediated genome editing by engineering split-Cas9 constructs, inteins, small molecules, protein-based dimerizing domains, and light-inducible systems. PMID- 26857073 TI - An accidental decapitation resulting from head protruding out of bus. AB - Decapitation is the separation of the head from the neck. Accidental decapitation is rare, and very few cases are cited in the literature. In this case, the victim was asleep during an overnight trip with her head sticking out of the window, and she was decapitated by a truck travelling in the opposite direction. Lack of security grilles on windows, high-speed driving, narrow roads and night travel were contributing factors. This case is presented for its rarity and pattern of injuries during the fatal mishap and to consider possible preventive measures. PMID- 26857074 TI - Bear-inflicted injuries - a report from Nepal. AB - Upper Mustang in the Northern Himalayan range of Nepal is the home of brown bears (Ursusarctos). Low-plant biomass as a result of scanty rainfall in Upper Mustang is a reason for habitat overlap of humans and wild animals. Humans who enter into the wild to collect firewood and graze cattle are liable to wild animal attacks. Such attacks, especially by brown bears, are readily identified by the type of injuries. These are more commonly confined to head and neck regions. Cutting, gnawing and tearing by sharp teeth and claws produces specific pattern of injuries, which are devastating but seldom fatal. This article reports a rare case of brown bear injury inflicted upon a man from the Upper Mustang region in Nepal. PMID- 26857075 TI - Medico-legal autopsy of abandoned foetuses and newborns in India. AB - Foeticide and the abandonment of newborns are important, albeit frequently neglected, issues. Concealment of childbirth is often seen in the setting of unwanted pregnancy which has been recognised as one of the most important factors in both cases. This study highlights the medico-legal autopsy findings of 238 abandoned foetuses and newborns over a period of 17 years (1996-2012) from the region of South Delhi, India. There was no sex predilection. The majority of the cases were full term. Nearly 35% of the foetuses were still born, about 29% were live born and the remainder were non-viable. Among the live born, death by homicide was more common than a natural death and most were left by the roadside. The abandoning and killing of newborns needs urgent attention, and strict measures are needed to save thousands of innocent lives. PMID- 26857076 TI - Fluorescein sodium as a contrast agent for colposcopy. PMID- 26857077 TI - Chronic kidney disease reduces risk of cardiovascular disease in patients with rheumatoid arthritis according to the QRISK lifetime cardiovascular risk calculator. PMID- 26857078 TI - In vitro pharmacodynamic modelling of anidulafungin against Candida spp. AB - The aim of this study was to fit anidulafungin in vitro static time-kill data from nine strains of Candida with a pharmacodynamic (PD) model in order to describe the antifungal activity of this drug against Candida spp. Time-kill data from strains of Candida albicans, Candida glabrata and Candida parapsilosis clades were best fit using an adapted sigmoidal Emax model and resulted in a set of PD parameters (Emax, EC50 and Hill factor) for each fungal strain. The data were analysed with NONMEM 7. Anidulafungin was effective in a species- and concentration-dependent manner against the strains of C. glabrata and C. parapsilosis clades as observed with the EC50 estimates. Maximum killing rate constant (Emax) values were higher against C. glabrata and C. parapsilosis complex strains. In conclusion, we demonstrated that the activity of anidulafungin against Candida can be accurately described using an adapted sigmoidal Emax model. PMID- 26857079 TI - [A resistant diarrhea]. PMID- 26857080 TI - [State of knowledge on sedentary behaviors]. AB - Sedentary behaviors refer to any waking activity characterized by an energy expenditure <= 1.5 metabolic equivalent and a sitting or lying posture. Recent epidemiological data reported that in North America and Europe, citizens spend between 8 and 11 hours sitting per day. Sedentary behaviors and physical activity can coexist in the same person. It is possible to spend a lot of time sitting each day while completing recommendations for regular physical activity. Adverse health effects of sedentary behaviors are in part independent of the physical activity level. The physiological implications associated with sedentary behaviors are mainly metabolic. Regulary interrupting the sedentary behavior has favorable effects on health, regardless the total time spent sitting. Many interventional perspectives for reducing sedentary behaviors in France can be envisaged. Some countries have already launched interesting large-scale prevention programs. PMID- 26857081 TI - [Strangulated obturator hernia simulating femoral hernia: A diagnostic challenge]. PMID- 26857082 TI - [Vulvar lymphangioma circumscriptum following pelvic radiotherapy]. PMID- 26857083 TI - [Oral angiomas]. AB - Hemangiomas are benign tumors that occur after a few days of life. The capillary malformations are isolated or constitute part of a complex angiomatosis. Venous malformations are low flow malformations with a blue color. They are of different types. The arteriovenous malformations are high flow lesions. They are difficult to treat. Lymphatic malformations are micro- or macrocystic. MRI is the gold standard for explorations. Some patients undergo maxillofacial surgical procedures and interventional radiology techniques for venous malformations, macrocystic lymphatic malformations, arteriovenous malformations. PMID- 26857084 TI - [Effectiveness of dog-assisted therapy in the elderly. A preliminary study]. AB - INTRODUCTION: Animal-assisted therapy is increasingly present in several educational and health areas. The aim of this study is to assess the effectiveness of such interventions in the elderly population living in residential settings. MATERIALS AND METHODS: A 12-week dog-assisted intervention program was designed, with 16 participants from a nursing home divided into an experimental group and a control group. RESULTS: Several physical and psychological variables were assessed before and after the intervention. While there were no significant differences in the control group, the experimental group improved significantly after participating in the program. DISCUSSION: The results support the hypothesis that animal-assisted interventions may be beneficial for residents in elderly care homes. PMID- 26857085 TI - [Developing a predictive model for the caregiver strain index]. AB - BACKGROUND: Patient homecare with multiple morbidities is an increasingly common occurrence. The caregiver strain index is tool in the form of questionnaire that is designed to measure the perceived burden of those who care for their families. The aim of this study is to construct a diagnostic nomogram of informal caregiver burden using data from a predictive model. METHODS: The model was drawn up using binary logistic regression and the questionnaire items as dichotomous factors. The dependent variable was the final score obtained with the questionnaire but categorised in accordance with that in the literature. Scores between 0 and 6 were labelled as "no" (no caregiver stress) and at or greater than 7 as "yes". The version 3.1.1R statistical software was used. To construct confidence intervals for the ROC curve 2000 boot strap replicates were used. RESULTS: A sample of 67 caregivers was obtained. A diagnosing nomogram was made up with its calibration graph (Brier scaled = 0.686, Nagelkerke R2=0.791), and the corresponding ROC curve (area under the curve=0.962). FINDINGS: The predictive model generated using binary logistic regression and the nomogram contain four items (1, 4, 5 and 9) of the questionnaire. R plotting functions allow a very good solution for validating a model like this. The area under the ROC curve (0.96; 95% CI: 0.994-0.941) achieves a high discriminative value. Calibration also shows high goodness of fit values, suggesting that it may be clinically useful in community nursing and geriatric establishments. PMID- 26857086 TI - Total shoulder arthroplasty using trabecular metal augments to address glenoid retroversion: the preliminary result of 10 patients with minimum 2-year follow up. AB - BACKGROUND: Options to address glenoid retroversion include eccentric reaming, bone grafting, modifications to component shape, and reverse shoulder arthroplasty. Trabecular metal (TM) augments have been used extensively in the hip and knee to address bone deficiency in arthroplasty as part of a hybrid combination of high-density polyethylene, polymethyl methacrylate, and TM. This study presents the initial results of the use of specifically designed augments in the shoulder to address glenoid retroversion as part of total shoulder arthroplasty (TSA). MATERIALS: Ten patients (4 women and 6 men; aged 60 to 79 years) with Walch grade B2 or C glenoids have undergone TM glenoid augment insertion as part of a TSA, with a longer than 24-month follow-up. Patients received a 15 degrees or 30 degrees TM wedge to correct excessive glenoid retroversion before the glenoid component was cemented. Outcome analysis was performed preoperatively, at 3, 6, and 12 months, and yearly thereafter. RESULTS: All patients have been satisfied, and all scores have improved. There have been no complications and no hardware failures or displacement. All glenoid components were implanted to within 10 degrees of neutral glenoid version. Radiographs at 24 months show good incorporation of the TM augment and the glenoid component. CONCLUSIONS: The TM augments have the advantage of immediate secure fixation, no tendency to collapse, and the ability to correct retroversion of 25 degrees or more. This study confirms the successful short-term outcome of wedge-shaped TM augments to correct glenoid retroversion as part of TSA. PMID- 26857087 TI - TiO2 Nanorod Array Constructed Nanotopography for Regulation of Mesenchymal Stem Cells Fate and the Realization of Location-Committed Stem Cell Differentiation. AB - As a physical cue for controlling the fate of stem cells, surface nanotopography has attracted much attention to improve the integration between implants and local host tissues and cells. A biocompatible surface TiO2 nanorod array is proposed to regulate the fate of bone marrow derived mesenchymal stem cells (MSCs). TiO2 substrates with different surface nanotopographies: a TiO2 nanorod array and a polished TiO2 ceramic are built by hydrothermal and sintering processes, respectively. The assessment of morphology, viability, gene expression, and protein characterization of the MSCs cultured on the different TiO2 substrates proves that a TiO2 nanorod array promotes the osteogenic differentiation of MSCs, while a TiO2 ceramic with a smooth surface suppresses it. Periodically assembled TiO2 nanorod array stripes on the smooth TiO2 ceramic are constructed by a combination of microfabrication and a chemical synthesis process, which realizes the location-committed osteogenic differentiation of MSCs. A route to control the differentiation of MSCs by a nanostructured surface, which can also control the location and direction of MSCs on the surface of biomaterials with micro-nano scale surface engineering, is demonstrated. PMID- 26857088 TI - [Changes in therapeutic targets and level of control of arterial hypertension: New evidence]. PMID- 26857089 TI - Influence of boat noises on escape behaviour of white-spotted eagle ray Aetobatus ocellatus at Moorea Island (French Polynesia). AB - The present study tested different sounds that could disturb eagle rays (Aetobatus ocellatus) during their foraging activities at Moorea, French Polynesia. Results showed that artificial white sound and single-frequency tones (40 Hz, 600 Hz or 1 kHz) did not have an effect on rays (at least 90% of rays continued to forage over sand), while playbacks of boat motor sound significantly disturbed rays during foraging activity (60% exhibited an escape behaviour). Overall, our study highlighted the negative effect of boat noises on the foraging activity of eagle rays. These noises produced by boat traffic could, however, have some positive effects for marine aquaculture if they could be used as a deterrent to repel the eagle rays, main predators of the pearl oysters. PMID- 26857090 TI - Marine turtles used to assist Austronesian sailors reaching new islands. AB - Austronesians colonized the islands of Rapa Nui, Hawaii, the Marquesas and Madagascar. All of these islands have been found to harbor Austronesian artifacts and also, all of them are known nesting sites for marine turtles. Turtles are well known for their transoceanic migrations, sometimes totalling thousands of miles, between feeding and nesting grounds. All marine turtles require land for nesting. Ancient Austronesians are known to have had outstanding navigation skills, which they used to adjust course directions. But these skills will have been insufficient to locate tiny, remote islands in the vast Indo-Pacific oceans. We postulate that the Austronesians must have had an understanding of the marine turtles' migration patterns and used this knowledge to locate remote and unknown islands. The depth and speed at which marine turtles migrate makes following them by outrigger canoes feasible. Humans have long capitalized on knowledge of animal behavior. PMID- 26857091 TI - Obesity decreases B cell responses in young and elderly individuals. AB - OBJECTIVE: To evaluate the effects of obesity-associated inflammation on influenza vaccine responses. METHODS: In young and elderly individuals, both lean and with obesity, antibody responses to influenza vaccination were measured. RESULTS: A decrease in in vivo vaccine responses, circulating switched memory, and transitional B cells and an increase in pro-inflammatory late/exhausted memory B cells were found. In vitro B cell function was measured by activation induced cytidine deaminase and E47, markers of optimal antibody responses. Moreover, IL-6 production was increased, whereas IL-10 production was decreased in cultures of B cells from individuals with obesity. Markers of immune activation (TNF-alpha, TLR4, micro-RNAs) in unstimulated B cells were also found increased and were negatively correlated with B cell function. In order to reveal potential mechanisms, we stimulated B cells from lean individuals in vitro with leptin, the adipokine increased in obesity. Leptin increased phospho-STAT3, crucial for TNF-alpha production, and decreased phospho-AMPK, the energy sensing enzyme upstream of phospho-p38 MAPK and E47. Leptin-induced phospho-STAT3 and phospho-AMPK levels were similar to those in B cells from individuals with obesity. CONCLUSIONS: These results demonstrate that leptin can be responsible for decreased B cell function in obesity. PMID- 26857092 TI - Controversies Surrounding Renal Denervation: Lessons Learned From Real-World Experience in Two United Kingdom Centers. AB - Renal denervation (RDN) is a therapy that targets treatment-resistant hypertension (TRH). The Renal Denervation in Patients With Uncontrolled Hypertension (Symplicity) HTN-1 and Symplicity HTN-2 trials reported response rates of >80%; however, sham-controlled Symplicity HTN-3 failed to reach its primary blood pressure (BP) outcome. The authors address the current controversies surrounding RDN, illustrated with real-world data from two centers in the United Kingdom. In this cohort, 52% of patients responded to RDN, with a 13+/-32 mm Hg reduction in office systolic BP (SBP) at 6 months (n=29, P=.03). Baseline office SBP and number of ablations correlated with office SBP reduction (R=-0.47, P=.01; R=-0.56, P=.002). RDN appears to be an effective treatment for some patients with TRH; however, individual responses are highly variable. Selecting patients for RDN is challenging, with only 10% (33 of 321) of the screened patients eligible for the study. Medication alterations and nonadherence confound outcomes. Adequate ablation is critical and should impact future catheter design/training. Markers of procedural success and improved patient selection parameters remain key research aims. PMID- 26857093 TI - Genome-wide association study in mice identifies loci affecting liver-related phenotypes including Sel1l influencing serum bile acids. AB - Using publicly available data from inbred mouse strains, we conducted a genome wide association study to identify loci that accounted for liver-related phenotypes between C57BL/6J and A/J mice fed a Paigen diet. We confirmed genome wide significant associations for hepatic cholesterol (chromosome 10A2) and serum total bile acid concentration (chromosome 12E) and identified a new locus for liver inflammation (chromosome 7C). Analysis of consomic mice confirmed that chromosome 12 A/J alleles accounted for the variance in serum total bile acid concentrations and had pleiotropic effects on liver mass, serum cholesterol, and serum alanine aminotransferase activity. Using an affected-only haplotype analysis among strains, we refined the chromosome 12E signal to a 1.95 Mb linkage disequilibrium block containing only one gene, sel-1 suppressor of lin-12-like (Sel1l). RNA sequencing and immunoblotting demonstrated that the risk allele locally conferred reduced expression of SEL1L in liver and distantly down regulated pathways associated with hepatocyte nuclear factor 1 homeobox A (Hnf1a) and hepatocyte nuclear factor 4A (Hnf4a), known modifiers of bile acid transporters and metabolic traits. Consistent with these data, knockdown of SEL1L in HepG2 cells resulted in reduced HNF1A and HNF4A and increased bile acids in culture media; it further captured multiple molecular signatures observed in consomic mouse livers with reduced SEL1L. Finally, dogs harboring a SEL1L mutation and Sel1l(+/-) mice fed a Paigen diet had significantly increased serum total bile acid concentrations, providing independent confirmation linking SEL1L to bile acid metabolism. CONCLUSION: Genetic analyses of inbred mouse strains identified loci affecting different liver-related traits and implicated Sel1l as a significant determinant of serum bile acid concentration. (Hepatology 2016;63:1943-1956). PMID- 26857094 TI - Oleoylethanolamide prevents neuroimmune HMGB1/TLR4/NF-kB danger signaling in rat frontal cortex and depressive-like behavior induced by ethanol binge administration. AB - Alcohol abuse is frequently characterized by a specific pattern of intake in binge drinking episodes, inducing neuroinflammation and brain damage. Here, we characterized the temporal profile of neuroinflammation in rats exposed to intragastric binge ethanol administrations (3 times/day * 4 days) and tested the anti-inflammatory/neuroprotective properties of the satiety factor oleoylethanolamide (OEA). Pre-treatment with OEA (5 mg/kg, i.p.) previous each alcohol gavage blocked the expression of high mobility group box 1 (HMGB1) danger signal and the innate immunity Toll-like receptors 4 (TLR4) in frontal cortex, and inhibited the nuclear factor-kappa B (NF-kB) proinflammatory cascade induced by alcohol binge administration. OEA reduced the levels of interleukin-1beta (IL 1beta), the monocyte chemoattractant protein-1 (MCP-1), and the enzymes cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) in ethanol binged animals. Elevations in plasma tumor necrosis factor alpha (TNF-alpha) and IL-1beta after ethanol were also inhibited by OEA. OEA also prevented ethanol induced lipid peroxidation, caspase-8 and pro-apoptotic caspase-3 activation in frontal cortex. Additionally, OEA blocked the rise in blood corticosterone levels after ethanol with no alteration in blood ethanol levels and may affect ethanol induced gut permeability for endotoxin. Finally, OEA, administered as a pre treatment during the ethanol binge, exerted antidepressant-like effects during acute withdrawal. Altogether, results highlight a beneficial profile of OEA as a potent anti-inflammatory, antioxidant, neuroprotective and antidepressant-like compound to treat alcohol abuse. PMID- 26857096 TI - Evidence of a skewed T-cell repertoire in patients with light chain amyloidosis. PMID- 26857095 TI - Properties of an optogenetic model for olfactory stimulation. AB - KEY POINTS: In olfactory research it is difficult to deliver stimuli with defined intensity and duration to olfactory sensory neurons. Expression of channelrhodopsin 2 (ChR2) in olfactory sensory neurons provides a means to activate these neurons with light flashes. Appropriate mouse models are available. The present study explores the suitability of an established olfactory marker protein (OMP)/ChR2-yellow fluorescent protein (YFP) mouse model for ex vivo experimentation. Expression of ChR2 in sensory neurons of the main olfactory epithelium, the septal organ and vomeronasal organ is characterized. Expression pattern of ChR2 in olfactory receptor neurons and the properties of light responses indicate that light stimulation does not impact on signal transduction in the chemosensory cilia. Light-induced electro-olfactograms are characterized with light flashes of different intensities, durations and frequencies. The impact of light-induced afferent stimulation on the olfactory bulb is examined with respect to response amplitude, polarity and low-pass filtering. ABSTRACT: For the examination of sensory processing, it is helpful to deliver stimuli in precisely defined temporal and spatial patterns with accurate control of stimulus intensity. This is challenging in experiments with the mammalian olfactory system because airborne odorants have to be transported into the intricate sensory structures of the nose and must dissolve in mucus to be detected by sensory neurons. Defined and reproducible activity can be generated in olfactory sensory neurons that express the light-gated ion channel channelrhodopsin 2 (ChR2). The neurons can be stimulated by light flashes in a controlled fashion by this optogenetic approach. Here we examined the application of an olfactory marker protein (OMP)/ChR2-yellow fluorescent protein (YFP) model for ex vivo exploration of the olfactory epithelium and the olfactory bulb of the mouse. We studied the expression patterns of ChR2 in the main olfactory system, the vomeronasal system, and the septal organ, and we found that ChR2 is absent from the sensory cilia of olfactory sensory neurons. In the olfactory epithelium, we characterized light induced electro-olfactograms with respect to peripheral encoding of stimulus intensity, stimulus duration and stimulus frequency. In acute slices of the olfactory bulb, we identified specific aspects of the ChR2-induced input signal, concerning its dynamic range, its low-pass filter property and its response to prolonged stimulation. Our study describes the performance of the OMP/ChR2-YFP model for ex vivo experimentation on the peripheral olfactory system and documents its versatility and its limitations for olfactory research. PMID- 26857097 TI - Sterilization Efficiency of a Novel Electrochemical Disinfectant against Staphylococcus aureus. AB - Disinfection of hazardous microorganisms that may challenge environmental safety is a crucial issue for economic and public health. Here, we explore the potential of a novel electrochemical disinfectant named plasma activated water (PAW), which was generated by nonthermal plasma, for inactivating Staphylococcus aureus (S. aureus). Meanwhile, the influence of bovine serum albumin (BSA) on the PAW disinfection efficacy was investigated. In the presence of BSA, PAW treatments achieved a reduction of S. aureus ranging from 2.1 to 5.5 Log, when without BSA it reached 7 Log. The sterilization efficacy depended on the PAW treatment time of S. aureus and plasma activation time for PAW generation. The results of electron spin resonance spectra showed the concentrations of hydroxyl radical (OH*) and nitric oxide radical (NO*) in water activated by plasma for 10 min (10 PAW) were higher than those in water activated by plasma for 5 min (5-PAW). Additionally, the physiological analysis of S. aureus demonstrated that the integrity of cell membrane, membrane potential, and intracellular pH homeostasis as well as DNA structure were damaged by PAW, and the molecule structure and chemical bonds of S. aureus were also altered due to PAW. Thus, PAW can be a promising chemical-free and environmentally friendly electrochemical disinfectant for application in the medical and food industries. PMID- 26857098 TI - Diagnostic value of sonography for detecting endometrial pathologies in postmenopausal women with and without bleeding. AB - PURPOSE: To investigate the diagnostic value of endometrial thickness measurement on sonography in predicting endometrial pathologies in postmenopausal women with vaginal bleeding and in those with asymptomatic thickened endometrium. METHODS: Six hundred two postmenopausal women with vaginal bleeding or asymptomatic thickened endometrium were evaluated in this study. Two hundred seventy-four women with postmenopausal bleeding regardless of endometrial thickness (group 1: symptomatic) and 328 women with an incidental finding of thickened endometrium (>=5 mm) without bleeding (group 2: asymptomatic) underwent endometrial biopsy for histopathologic examination. The receiver operating characteristics curves of endometrial thickness measurement for prediction of endometrial pathologies were analyzed. RESULTS: Endometrial carcinoma was detected in eight women (2.9%) in group 1 and in three (0.9%) in group 2. The best cutoff point for endometrial thickness in predicting endometrial carcinoma in group 1 was 8.2 mm, which provided 75% sensitivity (95% confidence interval [CI], 40.9-92.9%) and 74% specificity (95% CI, 68-78.5%); area under the receiver operating characteristics curve (AUC), 0.88; 95% CI, 0.76-1.00%; p = 0.0001. In group 2, the AUC was 0.76 (95% CI, 0.46-1.00; p = 0.114); the evidence was inconclusive as to the relationship between endometrial thickness and malignancy. For the prediction of polyps, the AUCs of endometrial thickness were 0.77 for group 1 (95% CI, 0.71 0.83%; p = 0.0001) and 0.61 for group 2 (95% CI, 0.54-0.67%; p = 0.002). CONCLUSIONS: Sonographically determined endometrial thickness measurement shows high diagnostic performance for detection of endometrial cancer in symptomatic postmenopausal women at the optimal cutoff thickness of approximately 8 mm, although the evidence supporting the use of sonography for predicting malignancy in asymptomatic women is inconclusive. For polyp detection, this technique shows moderate diagnostic ability in symptomatic women, but its predictive value is low in asymptomatic women. (c) 2016 Wiley Periodicals, Inc. J Clin Ultrasound 44:339 346, 2016. PMID- 26857099 TI - Implantable Neurostimulation for Headache Disorders: Effect on Healthcare Utilization and Expenditures. AB - OBJECTIVES: Chronic daily headache is a considerable source of morbidity for patients and also carries an enormous economic burden. Patients who fail standard medication regimens lack well-defined therapies, and neurostimulation is an emerging option for these patients. The purpose of this study was to analyze the cost utility of implantable neurostimulation for treatment of headache. METHODS: We utilized the Thompson Reuters Marketscan Data base to identify individuals diagnosed with headache disorders who underwent percutaneous neurostimulation. Healthcare expenditures for individuals who subsequently received permanent, surgically implanted neurostimulatory devices were compared to those who did not. Only individuals who sought implantable neurostimulation were included to account for headache severity. The cohorts were adjusted for comorbidity and prior headache-related expenses. Costs were modeled longitudinally using a generalized estimating equation. RESULTS: A total of 579 patients who underwent percutaneous trial of neurostimulation were included, of which 324 (55.96%) converted to permanent neurostimulation within one year. Unadjusted expenditures were greater for patients who underwent conversion to the permanent neurostimulation device, as expected. Costs grew at a lower rate for patients who converted to permanent device implantation. Cost neutrality for patients receiving the permanent device was reached in less than five years after the enrollment date. The mean cost of conversion to a permanent implantation was $18,607.53 (SD $26,441.34). CONCLUSIONS: Our study suggests that implantable neurostimulation reduces healthcare expenditures within a relatively short time period in patients with severe refractory headache. PMID- 26857100 TI - Response to "Recurrent Aphthous Stomatitis As a Marker of Celiac Disease in Children". PMID- 26857101 TI - Surgical Treatment of Patent Multilocular Saphenous Vein Graft Aneurysms After Coronary Artery Bypass Grafting. PMID- 26857102 TI - Retention of solute and particle markers in the digestive tract of chinchillas (Chinchilla laniger). AB - The chinchilla (Chinchilla laniger) is a herbivorous hystricomorph South American rodent for which no mean digesta retention times have been reported so far. Six animals (mean body mass +/- standard deviation: 513 +/- 99 g) on a diet of grass hay and lucerne-based pellets were given a pulse dose of a solute (cobalt-EDTA) and a particle (chromium-mordanted fibre, <2 mm) marker with subsequent frequent faecal collection. Dry matter intake was 45.2 +/- 8.0 g/kg(0.75) /day. Mean retention times were 22.2 +/- 5.3 h for solutes and 25.4 +/- 5.2 h for particles, with the difference being not significant within individuals. This indicates the presence of a 'mucus-trap' colonic separation mechanism, which is in accord with morphological descriptions of the typical colonic furrow in chinchillas. Corresponding to a strategy of colonic digesta separation and caecotroph formation, secondary marker excretion peaks indicated coprophagic events that were spaced approximately 12 h apart. Given that these retention times appear longer than measures reported for rabbits (Oryctolagus cuniculus) or guinea pigs (Cavia procellus), it would be interesting to compare the digestive efficiency of chinchillas on high levels of dietary fibre to other species. PMID- 26857103 TI - Interdisciplinary care programme to improve self-management for cancer patients undergoing stem cell transplantation: a prospective non-randomised intervention study. AB - The purpose of this single-centre prospective non-randomised study was to evaluate the effectiveness of an interdisciplinary care programme to enhance self management in patients with haematopoietic stem cell transplantation (HSCT). Patients undergoing HSCT, aged >14 years with informed consent were recruited (n = 79). Patients in the intervention group (IG) received standard care plus the SCION-HSCT intervention to counteract three problems after HSCT: muscle weakness, oral mucositis and malnutrition. Control group patients received standard care. Primary endpoint was global health-related quality of life (HRQoL) at discharge (EORTC QLQ C30 v. 3.0). Baseline characteristics were balanced between both groups, except physical performance (ECOG) being significantly lower for patients of the IG. At discharge, no group differences could be seen regarding HRQoL. Non confirmatory post hoc analyses showed for patients of the IG a shorter duration of hospitalisation (MD -10.90; 95% CI -18.05 to -3.75) and increased activity during hospitalisation (MD 2.44; 95% CI 1.27-3.61). In conclusion, clinical effectiveness of the intervention could not be proven with respect to the aspired improvement of HRQoL. However, the nurse-led interdisciplinary caring programme could be carried out in every day ward routine. Further research should focus on working mechanisms of complex interventions aiming to improve HRQoL of patients undergoing HSCT. PMID- 26857104 TI - Expectations and patients' experiences of obesity prior to bariatric surgery: a qualitative study. AB - OBJECTIVES: This study aimed to understand the experiences and expectations of people seeking bariatric surgery in England and identify implications for behavioural and self-management interventions. DESIGN: A qualitative study using modified photovoice methods, triangulating photography with semistructured indepth interviews analysed using framework techniques. SETTING: Areas served by two bariatric surgery multidisciplinary teams in the north of England. PARTICIPANTS: 18 adults (14 women and 4 men) who accepted for bariatric surgery, and were aged between 30 and 61 years. Participants were recruited through hospital-based tier 4 bariatric surgery multidisciplinary teams. RESULTS: The experiences of participants indicates the nature and extent of the burden of obesity. Problems included stigmatisation, shame, poor health, physical function and reliance on medications. Participants expected surgery to result in major physical and psychological improvement. They described how this expectation was rooted in their experiences of stigma and shame. These feelings were reinforced by previous unsuccessful weight loss attempts. Participants expected extreme and sometimes unrealistic levels of sustained weight loss, as well as improvements to physical and mental health. The overall desire and expectation of bariatric surgery was of 'normality'. Participants had received previous support from clinicians and in weight management services. However, they reported that their expectations of surgery had not been reviewed by services, and expectations appeared to be unrealistic. Likewise, their experience of stigmatisation had not been addressed. CONCLUSIONS: The unrealistic expectations identified here may negatively affect postoperative outcomes. The findings indicate the importance of services addressing feelings of shame and stigmatisation, and modifying patient's expectations and goals for the postoperative period. PMID- 26857105 TI - Bibliometric analysis of the top-cited gastroenterology and hepatology articles. AB - OBJECTIVE: To identify the top-cited articles in gastroenterology and hepatology, and analyse their characteristics. METHODS: Two searches were conducted in the Science Citation Index Expanded database; a search of 69 journals under the category 'Gastroenterology and Hepatology' (list A) and a keyword search of all journals (list B). The search results were analysed and the inter-rater coefficient of agreement between evaluators was measured using Cohen kappa. RESULTS: The number of citations varied from 1049 to 2959 in list A and from 1929 to 5500 in list B. In both lists, the majority of articles were research papers. No significant correlations were found between the number of citations and the number of years since publication (R(2)=0.00992, p=0.473 and R(2)=0.00202, p=0.757, respectively). However, the mean number of citations of papers published before the year 2000 was lower than those published after 2000 (36.70 +/- 19.31 vs 106.03 +/- 39.22). No correlation was found between number of authors and the number of citations (R(2)=0.04352, p=0.130), but strong correlations were found between the number of institutes involved or number of countries and the number of citations (R(2)=0.275, p<0.001 and R(2)=0.16181, p=0.003, respectively). Females were under-represented in authorship (45 vs 254, p=0.004). Only 21 papers (of 54) in list A were supported by grants. No correlation was found between number of grants received and the number of citations (R(2)=0.02573, p=0.247). The inter-rater agreement between evaluators had a Cohen kappa coefficient 0.76 0.84. CONCLUSIONS: Top-cited articles were not only published in highly ranked journals specialising in Gastroenterology and Hepatology but also in 14 journals not specialised in this field. The number of citations correlated with the number of institutes and the number of countries involved but not with the number of grants received or the number of authors. Females were under-represented in the authorship. PMID- 26857106 TI - Social inequalities in prevalence of diagnosed and undiagnosed diabetes and impaired glucose regulation in participants in the Health Surveys for England series. AB - OBJECTIVES: To ascertain the extent of socioeconomic and health condition inequalities in people with diagnosed and undiagnosed diabetes and impaired glucose regulation (IGR) in random samples of the general population in England, as earlier diagnosis of diabetes and treatment of people with IGR can reduce adverse sequelae of diabetes. Various screening instruments were compared to identify IGR, in addition to undiagnosed diabetes. DESIGN: 5, annual cross sectional health examination surveys; data adjusted for complex survey design. SETTING: Random selection of private homes across England, new sample annually 2009-2013. PARTICIPANTS: 5, nationally representative random samples of the general, free-living population: >= 1 adult interviewed in 24,254 of 36,889 eligible addresses selected. 18,399 adults had a valid glycated haemoglobin (HbA1c) measurement and answered the diabetes questions. MAIN OUTCOME MEASURES: Diagnosed diabetes, undiagnosed diabetes (HbA1c >= 48 mmol/mol), IGR (HbA1c 42-47 mmol/mol). RESULTS: Overall, 11% of the population had IGR, 2% undiagnosed and 6% diagnosed diabetes. Age-standardised prevalence was highest among Asian (19% (95% CI 16% to 23%), 3% (2% to 5%) and 12% (9% to 16%) respectively) and black participants (17% (13% to 21%), 2% (1% to 4%) and 14% (9% to 20%) respectively). These were also higher among people with lower income, less education, lower occupational class and greater deprivation. Education (OR 1.49 (95% CI 1.27 to 1.74) for no qualifications vs degree or higher) and income (1.35 (1.12 to 1.62) for lowest vs highest income quintile) remained significantly associated with IGR or undiagnosed diabetes on multivariate regression. The greatest odds of IGR or undiagnosed diabetes were with increasing age over 34 years (eg, OR 18.69 (11.53 to 30.28) aged 65-74 vs 16-24). Other significant associations were ethnic group (Asian (3.91 (3.02 to 5.05)), African-American (2.34 (1.62 to 3.38)) or 'other' (2.04 (1.07 to 3.88)) vs Caucasian); sex (OR 1.32(1.19 to 1.46) for men vs women); body mass index (3.54 (2.52 to 4.96) for morbidly obese vs not overweight); and waist circumference (2.00 (1.67 to 2.38) for very high vs low). CONCLUSIONS: Social inequalities in hyperglycaemia exist, additional to well known demographic and anthropometric risk factors for diabetes and IGR. PMID- 26857108 TI - Refocusing on physical health: Community psychiatric nurses' perceptions of using enhanced health checks for people with severe mental illness. AB - In the present qualitative, descriptive study, we explored Hong Kong community psychiatric nurses' (CPN) perceptions of using comprehensive physical health checks for service users diagnosed with severe mental illness (SMI). Research interviews were conducted with a purposive sample of 11 CPN in order to explore their perceptions about the use of the Health Improvement Profile (HIP) over a 1 year period. Interview data were analysed using inductive thematic analysis. The analysis revealed that the majority of CPN appreciated the comprehensive focus on the physical health of their clients and reported positive changes in their clinical practice. Many of them observed an increase in the motivation of their clients to improve their physical health, and also noted observable benefits in service users' well-being. The use of the HIP also helped the CPN identify implementation barriers, and highlighted areas of the tool that required modifications to suit the local cultural and clinical context. To our knowledge, this is the first study conducted in an Asian mental health service that explores nurses' views about using comprehensive health checks for people with SMI. The findings suggest that such approaches are viewed as being acceptable, feasible, and potentially beneficial in the community mental health setting. PMID- 26857107 TI - Randomised controlled pilot study to assess the feasibility of a Mediterranean Portfolio dietary intervention for cardiovascular risk reduction in HIV dyslipidaemia: a study protocol. AB - INTRODUCTION: HIV drug treatment has greatly improved life expectancy, but increased risk of cardiovascular disease remains, potentially due to the additional burdens of infection, inflammation and antiretroviral treatment. The Mediterranean Diet has been shown to reduce cardiovascular risk and mortality in the general population, but no evidence exists for this effect in the HIV population. This study will explore the feasibility of a randomised controlled trial (RCT) to examine whether a Mediterranean-style diet that incorporates a portfolio of cholesterol-lowering foods, reduces cardiovascular risk in people with HIV dyslipidaemia. METHODS AND ANALYSIS: 60 adults with stable HIV infection on antiretroviral treatment and low-density lipoprotein cholesterol >3 mmol/L will be recruited from 3 West Midlands HIV services. Participants will be randomised 1:1 to 1 of 2 dietary interventions, with stratification by gender and smoking status. Participants allocated to Diet1 will receive advice to reduce saturated fat intake, and those to Diet2 on how to adopt the Mediterranean Portfolio Diet with additional cholesterol-lowering foods (nuts, stanols, soya, oats, pulses). Measurements of fasting blood lipids, body composition and arterial stiffness will be conducted at baseline, and month 6 and 12 of the intervention. Food intake will be assessed using the Mediterranean Diet Score, 3 day food diaries and metabolomic biomarkers. Questionnaires will be used to assess quality of life and process evaluation. Qualitative interviews will explore barriers and facilitators to making dietary changes, and participant views on the intervention. Qualitative data will be analysed using the Framework Method. Feasibility will be assessed in terms of trial recruitment, retention, compliance to study visits and the intervention. SD of outcomes will inform the power calculation of the definitive RCT. ETHICS: The West Midlands Ethics Committee has approved this study and informed consent forms. This trial is the first to test cholesterol-lowering foods in adults with HIV. TRIAL REGISTRATION NUMBER: ISRCTN32090191; Pre-results. PMID- 26857110 TI - Fetal growth patterns in Beckwith-Wiedemann syndrome. AB - We provide data on fetal growth pattern on the molecular subtypes of Beckwith Wiedemann syndrome (BWS): IC1 gain of methylation (IC1-GoM), IC2 loss of methylation (IC2-LoM), 11p15.5 paternal uniparental disomy (UPD), and CDKN1C mutation. In this observational study, gestational ages and neonatal growth parameters of 247 BWS patients were compared by calculating gestational age corrected standard deviation scores (SDS) and proportionality indexes to search for differences among IC1-GoM (n = 21), UPD (n = 87), IC2-LoM (n = 147), and CDKN1C mutation (n = 11) patients. In IC1-GoM subgroup, weight and length are higher than in other subgroups. Body proportionality indexes display the following pattern: highest in IC1-GoM patients, lowest in IC2-LoM/CDKN1C patients, intermediate in UPD ones. Prematurity was significantly more prevalent in the CDKN1C (64%) and IC2-LoM subgroups (37%). Fetal growth patterns are different in the four molecular subtypes of BWS and remarkably consistent with altered gene expression primed by the respective molecular mechanisms. IC1-GoM cases show extreme macrosomia and severe disproportion between weight and length excess. In IC2-LoM/CDKN1C patients, macrosomia is less common and associated with more proportionate weight/length ratios with excess of preterm birth. UPD patients show growth patterns closer to those of IC2-LoM, but manifest a body mass disproportion rather similar to that seen in IC1-GoM cases. PMID- 26857111 TI - The Tapley and Bryden test of performance differences between the hands: The original data, newer data, and the relation to pegboard and other tasks. AB - Tapley and Bryden (T&B)'s 1985 circle-marking task is a group-administered task assessing performance differences between the hands. The bimodal distribution clearly separates self-described right- and left-handers. Using Phil's original datafiles we analyse the test in more detail, providing raw scores for each hands which are useful forensically, and we provide reliability estimates. Van Horn's unpublished 1992 PhD thesis studied T&B tasks and Annett pegboards varying in difficulty. A striking finding, that Phil Bryden called "the Van Horn problem," was that hand differences (R - L) were unrelated to task difficulty. That result was the starting point for Pamela Bryden's 1998 thesis, firstly replicating Van Horn, but then showing that task difficulty did relate to hand differences for Grooved pegboards. Pamela Bryden's model for those effects is presented here. Comparing across tasks, the T&B and pegboard tasks showed almost complete consistency for direction of handedness. Likewise, within each task, degree of handedness intercorrelated strongly across variants. In strong contrast, degree of handedness for T&B tasks showed minimal correlation with degree of handedness for pegboards. At the highest level, therefore, direction of handedness is consistent within individuals (conventional right and left handedness), but there are separable processes determining dominant-non-dominant hands differences for each particular task. PMID- 26857109 TI - Effects of initial graft tension on clinical outcome after anatomic double-bundle anterior cruciate ligament reconstruction: comparison of two graft tension protocols. AB - BACKGROUND: In anatomic double-bundle anterior cruciate ligament (ACL) reconstruction, there are great controversies concerning the ideal graft tension protocols. The purpose of this study was to clarify differences in the effect of two graft tension protocols on the clinical outcome after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction by comparing the minimum 2-year clinical results. METHODS: Ninety-seven patients with unilateral anatomic double bundle ACL reconstruction were divided into two groups. In the first 44 patients (Group I), a 40-N tension was applied to each of the two hamstring autografts at 30 degrees of knee flexion, and simultaneously fixed onto the tibia. In the remaining 53 patients (Group II), a 30-N tension was applied to each graft at 10 degrees of knee flexion, and simultaneously fixed onto the tibia. Each patient was examined 2 years after surgery. RESULTS: There wasn't a significant difference in the background of the two groups. There was no significant difference in the postoperative anterior laxity between the two groups. The average was 1.1 mm and 0.9 mm in Groups I and II, respectively. There wasn't any differences between the two groups in Lysholm knee score, International Knee Documentation Committee (IKDC) evaluation and muscle strength. Four patients had loss of knee extension in a range of 5 degrees and 10 degrees in Group I and none of the patients in Group II exhibited any loss in knee extension; which was statistically significant (p = 0.025). CONCLUSION: The two initial graft tension protocols did not result in any significant differences in the Lysholm knee score and IKDC grade. However, it was noted that the 40-N tension applied to each graft at 30 degrees of knee flexion more significantly induced loss of knee extension in comparison to the 30-N tension applied to each graft at 10 degrees . From a clinical viewpoint, the loss of knee extension is one of the pathological conditions that should be absolutely avoided after ACL reconstruction. Therefore, the 30-N tension applied to each graft at 10 degrees is preferable to the other graft tension protocol. PMID- 26857112 TI - A scoping review on the conduct and reporting of scoping reviews. AB - BACKGROUND: Scoping reviews are used to identify knowledge gaps, set research agendas, and identify implications for decision-making. The conduct and reporting of scoping reviews is inconsistent in the literature. We conducted a scoping review to identify: papers that utilized and/or described scoping review methods; guidelines for reporting scoping reviews; and studies that assessed the quality of reporting of scoping reviews. METHODS: We searched nine electronic databases for published and unpublished literature scoping review papers, scoping review methodology, and reporting guidance for scoping reviews. Two independent reviewers screened citations for inclusion. Data abstraction was performed by one reviewer and verified by a second reviewer. Quantitative (e.g. frequencies of methods) and qualitative (i.e. content analysis of the methods) syntheses were conducted. RESULTS: After searching 1525 citations and 874 full-text papers, 516 articles were included, of which 494 were scoping reviews. The 494 scoping reviews were disseminated between 1999 and 2014, with 45% published after 2012. Most of the scoping reviews were conducted in North America (53%) or Europe (38%), and reported a public source of funding (64%). The number of studies included in the scoping reviews ranged from 1 to 2600 (mean of 118). Using the Joanna Briggs Institute methodology guidance for scoping reviews, only 13% of the scoping reviews reported the use of a protocol, 36% used two reviewers for selecting citations for inclusion, 29% used two reviewers for full-text screening, 30% used two reviewers for data charting, and 43% used a pre-defined charting form. In most cases, the results of the scoping review were used to identify evidence gaps (85%), provide recommendations for future research (84%), or identify strengths and limitations (69%). We did not identify any guidelines for reporting scoping reviews or studies that assessed the quality of scoping review reporting. CONCLUSION: The number of scoping reviews conducted per year has steadily increased since 2012. Scoping reviews are used to inform research agendas and identify implications for policy or practice. As such, improvements in reporting and conduct are imperative. Further research on scoping review methodology is warranted, and in particular, there is need for a guideline to standardize reporting. PMID- 26857113 TI - Platelet activation independent of pulmonary inflammation contributes to diesel exhaust particulate-induced promotion of arterial thrombosis. AB - BACKGROUND: Accelerated thrombus formation induced by exposure to combustion derived air pollution has been linked to alterations in endogenous fibrinolysis and platelet activation in response to pulmonary and systemic inflammation. We hypothesised that mechanisms independent of inflammation contribute to accelerated thrombus formation following exposure to diesel exhaust particles (DEP). METHODS: Thrombosis in rats was assessed 2, 6 and 24 h after administration of DEP, carbon black (CB; control carbon nanoparticle), DQ12 quartz microparticles (to induce pulmonary inflammation) or saline (vehicle) by either intra-tracheal instillation (0.5 mg, except Quartz; 0.125 mg) or intravenous injection (0.5 mg/kg). Thrombogenicity was assessed by carotid artery occlusion, fibrinolytic variables and platelet-monocyte aggregates. Measures of inflammation were determined in plasma and bronchoalveolar lavage fluid. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI)-1 were measured following direct in vitro exposure of human umbilical vein endothelial cells (HUVECs) to DEP (10-150 MUg/mL). RESULTS: Instillation of DEP reduced the time to thrombotic occlusion in vivo, coinciding with the peak of DEP-induced pulmonary inflammation (6 h). CB and DQ12 produced greater inflammation than DEP but did not alter time to thrombotic occlusion. Intravenous DEP produced an earlier (2 h) acceleration of thrombosis (as did CB) without pulmonary or systemic inflammation. DEP inhibited t-PA and PAI-1 release from HUVECs, and reduced the t-PA/PAI-1 ratio in vivo; similar effects in vivo were seen with CB and DQ12. DEP, but not CB or DQ12, increased platelet-monocyte aggregates. CONCLUSION: DEP accelerates arterial thrombus formation through increased platelet activation. This effect is dissociated from pulmonary and systemic inflammation and from impaired fibrinolytic function. PMID- 26857114 TI - Blended Polyurethane and Tropoelastin as a Novel Class of Biologically Interactive Elastomer. AB - Polyurethanes are versatile elastomers but suffer from biological limitations such as poor control over cell attachment and the associated disadvantages of increased fibrosis. We address this problem by presenting a novel strategy that retains elasticity while modulating biological performance. We describe a new biomaterial that comprises a blend of synthetic and natural elastomers: the biostable polyurethane Elast-Eon and the recombinant human tropoelastin protein. We demonstrate that the hybrid constructs yield a class of coblended elastomers with unique physical properties. Hybrid constructs displayed higher elasticity and linear stress-strain responses over more than threefold strain. The hybrid materials showed increased overall porosity and swelling in comparison to polyurethane alone, facilitating enhanced cellular interactions. In vitro, human dermal fibroblasts showed enhanced proliferation, while in vivo, following subcutaneous implantation in mice, hybrid scaffolds displayed a reduced fibrotic response and tunable degradation rate. To our knowledge, this is the first example of a blend of synthetic and natural elastomers and is a promising approach for generating tailored bioactive scaffolds for tissue repair. PMID- 26857116 TI - Technology-driven diagnostics: From smart doctor to smartphone. AB - This review explores recent innovations in four seemingly unrelated areas of medical diagnostics, which, when used concurrently, promise to revolutionize the future of medicine. Novel microfluidics and microelectronics, combined with smartphones, allow individuals to test themselves at anytime and anywhere, thus providing instant health information. An emerging development is the availability of genomic testing directly to consumers for assessing disease predisposition. Some organizations have opened diagnostic laboratories in pharmacies and other public outlets, are encouraging consumers to test themselves, and claim that by doing so consumers will be empowered to diagnose the early disease that could be effectively treated or prevented. Another recent development is the initiation of large studies that aim to better understand wellness and disease processes, through the frequent and sometimes continuous monitoring of hundreds or thousands of parameters. These are then analyzed by health coaches who advise participants on follow-up steps to correct the abnormalities and return to wellness. A number of these approaches have now entered the health market and the services can be purchased. It is highly likely that further technological innovations will contribute to the popularity of these approaches among millions of health conscious consumers. However, the evidence for the effectiveness of these strategies to prevent or detect early disease, or to promote wellness, does not yet exist. We here analyze the perceived benefits and (neglected) harms of these approaches, in an effort to balance the optimism about their utility, until the evidence for their benefit is clearly demonstrated. PMID- 26857115 TI - Validation of an integrated pedal desk and electronic behavior tracking platform. AB - BACKGROUND: This study tested the validity of revolutions per minute (RPM) measurements from the Pennington Pedal DeskTM. Forty-four participants (73 % female; 39 +/- 11.4 years-old; BMI 25.8 +/- 5.5 kg/m(2) [mean +/- SD]) completed a standardized trial consisting of guided computer tasks while using a pedal desk for approximately 20 min. Measures of RPM were concurrently collected by the pedal desk and the Garmin Vector power meter. After establishing the validity of RPM measurements with the Garmin Vector, we performed equivalence tests, quantified mean absolute percent error (MAPE), and constructed Bland-Altman plots to assess agreement between RPM measures from the pedal desk and the Garmin Vector (criterion) at the minute-by-minute and trial level (i.e., over the approximate 20 min trial period). RESULTS: The average (mean +/- SD) duration of the pedal desk trial was 20.5 +/- 2.5 min. Measures of RPM (mean +/- SE) at the minute-by-minute (Garmin Vector: 54.8 +/- 0.4 RPM; pedal desk: 55.8 +/- 0.4 RPM) and trial level (Garmin Vector: 55.0 +/- 1.7 RPM; pedal desk: 56.0 +/- 1.7 RPM) were deemed equivalent. MAPE values for RPM measured by the pedal desk were small (minute-by-minute: 2.1 +/- 0.1 %; trial: 1.8 +/- 0.1 %) and no systematic relationships in error variance were evident by Bland-Altman plots. CONCLUSION: The Pennington Pedal DeskTM provides a valid count of RPM, providing an accurate metric to promote usage. PMID- 26857117 TI - Red cell distribution width predicts totally occluded infarct-related artery in NSTEMI. AB - Objective Since non-ST segment elevation myocardial infarction (NSTEMI) patients with totally occluded infarct-related artery (TO-IRA) have worse prognosis, it is important to recognize TO-IRA in NSTEMI. Red cell distribution width (RDW) and mean platelet volume (MPV) are novel markers of inflammation and oxidative stress and were associated with poor clinical outcomes in acute coronary syndrome. In the present study, association of RDW and MPV with the presence of TO-IRA in NSTEMI was investigated. Methods Data of 201 consecutive patients who underwent coronary angiography with a diagnosis of NSTEMI were analyzed. Independent predictors of TO-IRA were investigated with logistic regression analysis. Results Sixty-six (32.8%) of the patients had TO-IRA. In patients with TO-IRA, RDW and troponin-T were significantly higher and left ventricular ejection fraction (LVEF) was lower. MPV did not differ between groups. Circumflex (CX) IRA was more common in TO-IRA group. The ROC curve analysis showed that the RDW at a cut-point of 13.95% has 76% sensitivity and 66% specificity in detecting TO-IRA. RDW, troponin-T, LVEF and CX-IRA were independent predictors of TO-IRA in NSTEMI, but MPV was not. Conclusion RDW is a cheap and readily available marker that may have a role to predict TO-IRA in NSTEMI. PMID- 26857118 TI - Protein Quality and Growth in Malnourished Children. AB - BACKGROUND: Protein quality refers to the amounts and ratios of essential amino acids in a food. Two methods most commonly used for determining protein quality are the protein digestibility-corrected amino acid score (PDCAAS) and the digestible indispensible amino acid score (DIAAS). OBJECTIVE: To use existing literature to compare different amino acid profiles and PDCAAS and DIAAS scores in individuals with acute inflammation and to assess their relationship with weight gain in children with severe acute malnourished (SAM). METHODS: A series stable isotope studies were previously conducted in children with SAM and acute infection, and these data were reviewed with respect to protein synthesis. Eleven published treatment trials for SAM with different therapeutic foods were analyzed to examine the relationship between protein quality scores with weight gain (g/kg/d). Protein scores were calculated with the PDCAAS and DIAAS amino acid reference patterns. A DIAAS score adjusted for the higher weight gain expected in malnourished children was also used. Bivariate correlation analysis was used to examine this relationship. RESULTS: The protein kinetic data supported the hypothesis that a balance of amino acids that matches the composition of acute phase proteins maximizes amino acid synthesis. Protein quality scores were highly correlated with the rate of weight gain in recovery from SAM, and the DIAAS scoring system adjusted for the higher expected weight gain had the strongest correlation with the observed weight gain. CONCLUSION: Protein quality scores must account for physiologic status so that they better match with needs and thus better promote health. PMID- 26857119 TI - An unusual case of pedunculated subserosal leiomyosarcoma of the uterus mimicking ovarian carcinoma. AB - BACKGROUND: Leiomyosarcoma of the uterus is an extremely rare but highly aggressive tumor that accounts for only 1-2 % of uterine malignancies, and is usually associated with a dismal outcome. CASE PRESENTATION: The authors present an unusual case of pedunculated subserosal leiomyosarcoma of the uterus mimicking ovarian carcinoma. A 57-year-old postmenopausal woman presented with progressive low abdominal pain and urinary frequency. Pelvic magnetic resonance imaging revealed a large adnexal mass with carcinomatosis peritonei. Laboratory examination revealed an elevated serum CA-125 level (398.4 U/ml). The patient underwent exploratory laparotomy under suspicion of ovarian malignancy. Frozen section indicated malignancy originating from the uterus, and thus, total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic lymph node dissection, and mass excision were performed. Subsequent histopathologic examination resulted in a final diagnosis of leiomyosarcoma of the uterus. The patient's postoperative course was uneventful, and gemcitabine and docetaxel adjuvant chemotherapy was administered. CONCLUSION: The authors report an unusual case of pedunculated subserosal leiomyosarcoma of the uterus mimicking ovarian carcinoma. PMID- 26857120 TI - Cholecystectomy in mild acute biliary pancreatitis: the sooner; the better. PMID- 26857123 TI - How Important Is Research on Pollution Levels in Antarctica? Historical Approach, Difficulties and Current Trends. AB - Despite the fact that Antarctica is a continent notably free from large negative impact of human activities, literature data can be the basis for concluding that this is not an area free from anthropogenic pollutants. Pollutants, which are identified in various elements of the environment of Antarctica, are mostly connected with long-range atmospheric transport (LRAT) and deposition in this area. The study presents: a historical overview of research pertaining to the presence of pollutants in entire Antarctica; a description of the development of research on pollutants in various environmental samples conducted in this area since 1960; a detailed description of contemporary analytical research (2000 2014); information on concentration levels of a broad range of pollutants present in various elements of the environment. The data collected can provide grounds for concluding that pollutants present in this area can contribute to gradual degradation of Antarctic ecosystem. PMID- 26857121 TI - An interlaboratory comparison of dosimetry for a multi-institutional radiobiological research project: Observations, problems, solutions and lessons learned. AB - PURPOSE: An interlaboratory comparison of radiation dosimetry was conducted to determine the accuracy of doses being used experimentally for animal exposures within a large multi-institutional research project. The background and approach to this effort are described and discussed in terms of basic findings, problems and solutions. METHODS: Dosimetry tests were carried out utilizing optically stimulated luminescence (OSL) dosimeters embedded midline into mouse carcasses and thermal luminescence dosimeters (TLD) embedded midline into acrylic phantoms. RESULTS: The effort demonstrated that the majority (4/7) of the laboratories was able to deliver sufficiently accurate exposures having maximum dosing errors of <=5%. Comparable rates of 'dosimetric compliance' were noted between OSL- and TLD based tests. Data analysis showed a highly linear relationship between 'measured' and 'target' doses, with errors falling largely between 0 and 20%. Outliers were most notable for OSL-based tests, while multiple tests by 'non-compliant' laboratories using orthovoltage X-rays contributed heavily to the wide variation in dosing errors. CONCLUSIONS: For the dosimetrically non-compliant laboratories, the relatively high rates of dosing errors were problematic, potentially compromising the quality of ongoing radiobiological research. This dosimetry effort proved to be instructive in establishing rigorous reviews of basic dosimetry protocols ensuring that dosing errors were minimized. PMID- 26857124 TI - The clinical consequences of sucrase-isomaltase deficiency. AB - Primary sucrase-isomaltase deficiency, originally thought to be a homozygous recessive disorder, has been found to have numerous genetic variants that alone or in combination (compound heterozygosity) express varying degrees of clinical illness, most commonly causing chronic diarrhea, abdominal pain, and bloating. These symptoms are also present with secondary sucrase-isomaltase deficiency. Recent investigations are providing evidence that sucrase-isomaltase deficiency is more prevalent and of greater clinical significance than previously suspected. Further research is required to correlate the specific genotypes and phenotypes with their clinical expressions and to determine the most appropriate treatment algorithm for these patients. PMID- 26857127 TI - Tuning the Mn valence state in new Ca(0.66)Mn(2-x)Al(x)O4 (x<= 0.4) oxides: impact on magnetic and redox properties. AB - New Ca(0.66)Mn(2-x)Al(x)O4 (x<= 0.4) solid solutions crystallizing with the CaFe2O4-type structure (SG: Pnma) were synthesized for the first time by the glycine-nitrate process. The structures were determined on the basis of XRD Rietveld analysis and electron diffraction investigation. While the CaMn3O6 ('Ca(0.66)Mn2O4') oxide adopts a monoclinic unit cell, the Al substitution for Mn (x = 0.2, 0.4) leads to an orthorhombic cell with only two Mn atomic positions, with different valence states, and 33% of Ca sites empty. The Ca molar concentration decreases down to 0.6 in order to increase the Mn valence leading to a phase mixture, whereas a slight Ca content increase up to 0.7 leads to a decrease of Mn valence in the pure phase. The Al(3+) ions are located at a specific Mn site because their ionic radii are close to that of Mn(4+) and a more isotropic environment. The unit cell parameters and volume strongly decrease for a low Al content and tend to an asymptotic value of x = 0.33-0.4, around the limit of solubility. As the Al content increases, the Mn valence state in the same slightly distorted octahedral site increases up to 4+ whereas the other octahedral site is highly elongated and corresponds mainly to Jahn-Teller Mn(3+). At x = 0.33, these two Mn sites correspond to Mn(4+) and Mn(3+) respectively. Moreover, the aluminium content increase induces a weakening of the global antiferromagnetic long range interactions between the ferromagnetic chains. The Al substitution leads to the change of the Mn valence distribution as well as the unit cell symmetry of the CaMn3O6 phase. These 1D tunnel networks stabilizing the Mn(3+)/Mn(4+) valence states can be reduced under Ar/5%H2 between T = 300 degrees C and T = 600 degrees C (heating rate = 2 degrees C min(-1)) into pure Mn(2+) rocksalt solid solution despite the large difference in ionic radii. The re-oxidation leads to the same CaFe2O4-type structure and several redox cycles can be operated. The relationship between the two double chains of the edge sharing octahedral sites and the rocksalt-type framework is clear and should appear as the driving force for the structural transformation during the reduction/oxidation processes. Finally, Al substitution allows an increasing of the Mn-O bond covalence and consequently the reduction in temperature. PMID- 26857125 TI - Effect of hepatic or renal impairment on the pharmacokinetics of evacetrapib. AB - PURPOSE: The aim of this study is to investigate the effect of hepatic or renal impairment on the pharmacokinetics of a single 130-mg evacetrapib dose. METHODS: Two open-label, parallel-design studies in males and females with normal hepatic function or Child-Pugh mild, moderate, or severe hepatic impairment, or with normal renal function or severe renal impairment. Non-compartmental pharmacokinetic parameters were estimated from plasma concentration-time data. Evacetrapib safety and tolerability were assessed. RESULTS: Pharmacokinetic parameter estimates were comparable between controls and mildly hepatically impaired subjects. Geometric mean area under the concentration-time curve (AUC) was greater, half-life (t1/2) was longer, and maximum concentration (Cmax) was lower in subjects with moderate and severe hepatic impairment than in controls. Apparent clearance (CL/F) did not differ between controls and those with mild hepatic impairment, but CL/F decreased for moderate and severe impairment. Spearman correlation coefficient showed no relationship between CL/F and Child Pugh score. In the renal study, AUC and t1/2 were similar between groups, while Cmax was 15 % lower in subjects with severe impairment. CL/F in severely renally impaired subjects differed by <6 % from that in controls. Spearman correlation coefficient showed no apparent relationship between CL/F and estimated creatinine clearance or glomerular filtration rate. Neither study noted changes in clinical laboratory parameters or clinically significant findings. Adverse event incidence was low, and all were mild or moderate in severity. CONCLUSION: Evacetrapib exposure did not differ between mild hepatic impairment and normal hepatic function, but increased along the progression from mild to moderate to severe hepatic impairment. Severe renal impairment did not affect evacetrapib exposure. PMID- 26857128 TI - Redescription and new locality record of Choleoeimeria turcicus from the gallbladder of Hemidactylus turcicus in Egypt, with notes on its endogenous development. AB - Upton et al. J Protozool 35:24-25, 1988 originally described Eimeria turcicus from the gallbladder of the Mediterranean gecko, Hemidactylus turcicus, in the USA. Shortly after establishing the genus Choleoeimeria, Paperna and Landsberg S Afr J Zool 24:345-355, 1989 transferred E. turcicus to this genus, renaming it as Choleoeimeria turcicus. This paper reports the findings of a survey of coccidian parasites of lizards in Egypt, during which tetrasporocystic oocysts were reported from the gallbladder of H. turcicus. Based on the oocysts' morphological and morphometric characteristics and the same host, it can be deduced for the first time that the present species is conspecific with E. turcicus. In the present study, the gallbladder was the sole site for the endogenous development and no endogenous stages were noticed in the intestine. The endogenous stages induce hypertrophy and displacement of the infected cells from the original biliary epithelium to form a prolonged and branching outgrowth. We therefore followed Paperna and Landsberg S Afr J Zool 24:345-355, 1989 and considered the biliary coccidium recorded in this study to be a member of the genus Choleoeimeria. This represents a new locality record for C. turcicus, which was previously known in the USA and Israel. PMID- 26857126 TI - The long-term association between physical activity and risk of dementia in the community: the Hisayama Study. AB - We investigated the long-term influence of physical activity on the risk of dementia in an elderly Japanese population. A total of 803 community-dwelling elderly Japanese individuals without dementia aged >=65 years were followed prospectively for 17 years. Physically active status was defined as engaging in exercise at least one or more times per week during leisure time, and participants were divided into an active group and an inactive group by the presence or absence of such physical activity. The risk estimates of physical activity on the development of all-cause dementia and its subtypes were computed using a Cox proportional hazards model. During the follow-up, 291 participants developed all-cause dementia. Of these, 165 had Alzheimer's disease (AD), 93 had vascular dementia (VaD), and 47 had other dementia. Compared with the inactive group, the active group showed significantly lower crude incidence of AD (21.8 vs. 14.2 per 1000 person-years, p = 0.01), but no significant differences were observed for all-cause dementia (35.6 vs. 30.5, p = 0.17), VaD (11.3 vs. 9.8, p = 049), and other dementia (4.6 vs. 7.1, p = 0.15). After adjusting for potential confounders, the relationship between physical activity and risk of AD remained significant (adjusted hazard ratio 0.59, 95% confidence interval 0.41-0.84, p = 0.003). Our findings suggest that physical activity reduces the long-term risk of dementia, especially AD, in the general Japanese population. PMID- 26857129 TI - First report of Eucoleus boehmi infection in a dog from Portugal. AB - Nasal eucoleosis is an uncommonly diagnosed parasitic infection in domestic dogs. Depending on the parasite load, dogs with Eucoleus boehmi may exhibit mild upper respiratory signs such as sneezing and nasal discharge or may not exhibit any clinical signs. The present study describes the case of a 6-year-old male dog, presented with reverse sneezing of 2 months' duration and bilateral nasal serous discharge. The patient had been taking prednisolone for years due to an immune mediated arthritis of the carpal joint. Physical examination, complete blood count, serum chemistry and thoracic radiography were unremarkable. A computed tomography scan of the nasal cavity was compatible with bilateral chronic rhinitis of unknown aetiology. Further investigation by rhinoscopy revealed diffuse erythematous mucosae with several white and serpentine-shaped worms on the turbinates' surface. Morphological identification of the worms collected in situ was performed, revealing filiform nematodes (15-30 mm in length) containing several bipolar plugged and barrel-shaped eggs in their medial segment. The eggs contained a multicellular embryo, a pitted surface and measured 54-60 MUm long by 30-35 MUm wide. Morphological and morphometric characteristics were consistent with E. boehmi. Treatment with imidacloprid/moxidectin spot-on formulation along with preventing measures to minimise reinfection were prescribed and successfully achieved, as confirmed by negative faecal examinations. To the best of the authors' knowledge, this represents the first report of E. boehmi infection in a dog from Portugal. Nasal eucoleosis appears to be underestimated and should be considered as a differential diagnosis in canids suffering from upper respiratory distress. PMID- 26857130 TI - Fecundity reduction of BALB/c mice after survival from lethal Neodiplostomum seoulense infection. AB - Neodiplostomum seoulense (Digenea: Neodiplostomidae), an intestinal trematode infecting humans and rodents, is known to be highly pathogenic and lethal to experimentally infected mice. Only a small proportion of mice can survive from its infection. This study aimed to assess the reproductive capacity of surviving BALB/c mice. The fertility of male and female mice, birth time (period from mating to birth of litters), number of litters, size and weight of testes or ovary-oviduct-uterus, apoptosis of testicular cells, and serum levels of sex hormones were determined. Our results revealed that surviving mice underwent severe fecundity reduction and finally became infertile. They could not be able to produce generations beyond F4. Fertility rate, birth time, and number of litters of N. seoulense-infected mice were all significantly (p < 0.05) lower than those of uninfected controls, Metagonimus miyatai (less pathogenic intestinal trematode)-infected, or castor oil (severe diarrheal agent) administered controls. The size and weight of testes or ovary-oviduct-uterus were markedly (p < 0.05) decreased after N. seoulense infection. Moreover, the number of apoptotic cells in the testicular tissue was significantly (p < 0.05) increased (up to 10-50-folds) during weeks 1-3 post-infection. Serum testosterone levels in infertile mice were reduced to 1/10 level of fertile mice. These results indicated that BALB/c mice surviving N. seoulense infection underwent destruction and apoptosis of gonad tissues with fecundity reduction. They were finally infertile, with no ability to produce their next generations. PMID- 26857131 TI - [Overview of dermatological registries in Germany]. PMID- 26857132 TI - [Eczematous disorders in adolescents]. AB - Eczematous disorders in adolescence (definition WHO: the period between 10 and 20 years) are common and include mainly atopic dermatitis, contact eczema, and seborrheic dermatitis. They all share the similarity of inflammatory reactions which mainly affect the epidermis and can take a chronic course, depending on the underlying dermatosis. In the following article, the particularities of eczematous diseases in adolescents are discussed. PMID- 26857133 TI - [Isolated epidermal cysts of the vulva]. AB - Vulvar cysts are rare und benign entities. They are epidermoid cysts which may develop following trauma or surgery. They can also spontaneously develop. They vary in number and size. They grow slowly and tend to show calcification. The treatment consists of surgical removal. Other methods are pinch-punch excision, heat application, and incision. PMID- 26857135 TI - Cryptosporidium ubiquitum, C. muris and Cryptosporidium deer genotype in wild cervids and caprines in the Czech Republic. PMID- 26857136 TI - Combined effect of starch/montmorillonite coating and passive MAP in antioxidant activity, total phenolics, organic acids and volatile of fresh-cut carrots. AB - This work evaluates fresh-cut carrots (FCC) coated with montmorillonite (MMT) subjected to passive modified atmosphere packaging. Carrots were sanitized, cooled, peeled and sliced. Half of the FCC were coated with MMT nanoparticle film and the other half were not. All FCCs were packed in a polypropylene rigid tray, covered with a polypropylene rigid lid or sealed with polyethylene + propylene film, in four treatments (RL, rigid lid; RLC, rigid lid + coating; ST, sealed tray; STC, sealed tray + coating). FCCs were stored at 4 degrees C and were analyzed weekly for 4 weeks (total antioxidant activity by 2,2-diphenyl-1-picryl hydrazyl method and the beta-carotene/linoleic acid, phenolic compounds, organic acids and volatile compounds). The use of coating film with starch nanoparticles and a modified atmosphere leads to the preservation of the total antioxidant activity, the volatile and organic acids of FCC. PMID- 26857134 TI - Antidepressant, antioxidant and neurotrophic properties of the standardized extract of Cocos nucifera husk fiber in mice. AB - The plant Cocos nucifera and its derivatives have shown antidepressant-like effects, although its hydroalcoholic extract has not been studied with this end in mind. Therefore, we decided to determine the antidepressant-like effects of the standardized hydroalcoholic extract of Cocos nucifera husk fiber (HECN) as well as oxidative alterations in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST), and the levels of brain-derived neurotrophic factor (BDNF) in the HC of mice. The extract was characterized based on the content of total polyphenols as well as two phenol compounds-catechin and chlorogenic acid-by HPLC PDA. Male animals were treated per os (p.o.) for 7 days with distilled water or HECN (50, 100 or 200 mg/kg), or intraperitoneally with vitamin E (Vit E 400 mg/kg). One hour after the last drug administration, the animals were submitted to the open field test, forced swimming test (FST), tail suspension test (TST) and, immediately after the behavioral tests, had their brain removed for neurochemical determinations. The results showed that HECN100 decreased the immobility time in the FST and TST presenting, thus demonstrating an antidepressant-like effect. The administration of HECN decreased malondialdehyde levels in all doses and brain areas studied with the exception of HECN50 in the HC. The administration of HECN also decreased nitrite levels in all doses and brain regions studied. HECN100 also increased the levels of BDNF in HC of mice. In conclusion, we demonstrated that HECN has antidepressant-like properties, probably based on its antioxidant and neurotrophic effects, and is thus relevant for the treatment of depression. PMID- 26857137 TI - RE: Modification of Occupational Exposures on Bladder Cancer Risk by Common Genetic Polymorphisms. PMID- 26857138 TI - Response. PMID- 26857139 TI - Haematospirillum jordaniae gen. nov., sp. nov., isolated from human blood samples. AB - A Gram-negative, aerobic, motile, spiral-shaped bacterium, strain H5569(T), was isolated from a human blood sample. Phenotypic and molecular characteristics of the isolate were investigated. Optimal growth was found to occur at 35 degrees C under aerobic conditions on Heart Infusion Agar supplemented with 5 % rabbit blood. The major fatty acids present in the cells were identified as C16:0, C16:1omega7c and C18:1omega7c. The predominant respiratory quinone was found to be ubiquinone-Q10. The G+C content of genomic DNA for strain H5569(T) was found to be 49.9 %. Based on 16S rRNA gene sequence analysis results, 13 additional isolates were also analysed in this study. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the organism, represented by strain H5569(T), forms a distinct lineage within the family Rhodospirillaceae, closely related to two Novispirillum itersonii subspecies (93.9-94.1 %) and two Caenispirillum sp. (91.2-91.6 %). Based on these results, the isolate H5569(T) is concluded to represent a new genus and species for which the name Haematospirillum jordaniae gen. nov., sp. nov. is proposed. The type strain is H5569(T) (=DSM(T) 28903 = CCUG 66838(T)). PMID- 26857141 TI - A three-component reagent system for rapid and mild removal of O-, N- and S trityl protecting groups. AB - A new reagent system consisting of a Lewis acid such as BF3.Et2O or Cu(OTf)2, the mild protic acid hexafluoroisopropanol and the reducing quenching agent triethylsilane was elaborated for O-, N- and S-detritylation of nucleoside, carbohydrate and amino acid derivatives. The method is compatible with acetyl, silyl, acetal and Fmoc groups. PMID- 26857140 TI - Bif-1 deficiency impairs lipid homeostasis and causes obesity accompanied by insulin resistance. AB - Bif-1 is a membrane-curvature inducing protein that is implicated in the regulation of autophagy and tumorigenesis. Here, we report that Bif-1 plays a critical role in regulating lipid catabolism to control the size of lipid droplets and prevent the development of obesity and insulin resistance upon aging or dietary challenge. Our data show that Bif-1 deficiency promotes the expansion of adipose tissue mass without altering food intake or physical activities. While Bif-1 is dispensable for adipose tissue development, its deficiency reduces the basal rate of adipose tissue lipolysis and results in adipocyte hypertrophy upon aging. The importance of Bif-1 in lipid turnover is not limited to adipose tissue since fasting and refeeding-induced lipid droplet clearance is also attenuated by Bif-1 loss in the liver. Interestingly, obesity induced by a high fat-diet or Bif 1 deficiency downregulates the expression of proteins involved in the autophagy lysosomal pathway, including Atg9a and Lamp1 in the adipose tissue. These findings thus identify Bif-1 as a novel regulator of lipid homeostasis to prevent the pathogenesis of obesity and its associated metabolic complications. PMID- 26857142 TI - [Triple Descemet membrane endothelial keratoplasty. Indications, variations and results]. AB - When Descemet membrane endothelial keratoplasty (DMEK) is indicated in patients with phakic eyes, a combination with phacoemulsification and intraocular lens implantation in one sitting should be considered as a triple DMEK. The best possible preoperative deswelling of the cornea should be strived for in order to allow sufficient viewing conditions for the individual stages of cataract surgery. Furthermore, technical details, e.g. regulation of pupillary width also must be considered. The power of the intraocular lens has to be adjusted in order to compensate for the shift of refraction towards hyperopic values induced by DMEK surgery. A rapid and clear improvement in visual acuity can normally be achieved after a triple DMEK. There seem to be no disadvantages compared with a two-stage procedure for DMEK and cataract surgery. PMID- 26857143 TI - Comprehensive transcriptomic and proteomic characterization of human mesenchymal stem cells reveals source specific cellular markers. AB - Mesenchymal stem cells (MSC) are multipotent cells with great potential in therapy, reflected by more than 500 MSC-based clinical trials registered with the NIH. MSC are derived from multiple tissues but require invasive harvesting and imply donor-to-donor variability. Embryonic stem cell-derived MSC (ESC-MSC) may provide an alternative, but how similar they are to ex vivo MSC is unknown. Here we performed an in depth characterization of human ESC-MSC, comparing them to human bone marrow-derived MSC (BM-MSC) as well as human embryonic stem cells (hESC) by transcriptomics (RNA-seq) and quantitative proteomics (nanoLC-MS/MS using SILAC). Data integration highlighted and validated a central role of vesicle-mediated transport and exosomes in MSC biology and also demonstrated, through enrichment analysis, their versatility and broad application potential. Particular emphasis was placed on comparing profiles between ESC-MSC and BM-MSC and assessing their equivalency. Data presented here shows that differences between ESC-MSC and BM-MSC are similar in magnitude to those reported for MSC of different origin and the former may thus represent an alternative source for therapeutic applications. Finally, we report an unprecedented coverage of MSC CD markers, as well as membrane associated proteins which may benefit immunofluorescence-based applications and contribute to a refined molecular description of MSC. PMID- 26857144 TI - Lithium inhibits tumor lymphangiogenesis and metastasis through the inhibition of TGFBIp expression in cancer cells. AB - Metastasis is the main cause of mortality in cancer patients. Although there are many anti-cancer drugs targeting tumor growth, anti-metastatic agents are rarely developed. Angiogenesis and lymphangiogenesis are crucial for cancer progression; in particular, lymphangiogenesis is pivotal for metastasis in cancer. Here we report that lithium inhibits colon cancer metastasis by blocking lymphangiogenesis. Lithium reduces the expression of transforming growth factor beta-induced protein (TGFBIp) in colon cancer cells by inhibiting Smad3 phosphorylation via GSK3beta inactivation. Moreover, lithium inhibits lymphatic endothelial cell migration, which is increased upon TGFBIp expression in tumor cells. Lithium had no significant effect on SW620 tumor growth in vitro and in vivo; however, it inhibited lymphangiogenesis in tumors. In tumor xenografts model, lithium was found to prevent metastasis to the lungs, liver, and lymph nodes by inhibiting TGFBIp-induced tumor lymphangiogenesis. Collectively, our findings demonstrate a novel role of lithium in the inhibition of colon cancer metastasis by blocking TGFBIp expression, and thereby TGFBIp-induced lymphangiogenesis, in primary tumors. PMID- 26857145 TI - Atypical small acinar proliferation (ASAP): Is a repeat biopsy necessary ASAP? A multi-institutional review. AB - BACKGROUND: Atypical small acinar proliferation (ASAP) occurs in approximately 5% of prostate biopsies. Approximately 30-40% of patients with ASAP may develop prostate cancer (PCa) within a 5-year period. Current guidelines recommend a repeat biopsy within 3-6 months after the initial diagnosis. Our objective was to examine the association between ASAP and subsequent diagnosis of high-grade PCa and to evaluate the need for immediate repeat biopsy. METHODS: A retrospective multi-institutional review identified 264 patients who underwent prostate biopsy from 2000 to 2013 (Brown), 2008 to 2013 (University of Massachusetts) and 1994 to 2005 (Mayo) and were diagnosed with ASAP. Patients underwent transrectal ultrasound-guided biopsies for elevated PSA and/or abnormal digital rectal exam. Clinicopathologic features were assessed, including rates of subsequent PCa detection of any high-grade (Gleason 7-10) PCa. Comparison was made between those with subsequent PCa on repeat biopsy and those with benign repeat pathology. RESULTS: All 264 patients included underwent repeat biopsy with a median follow up of 5.4 years (interquartile range: 4.6, 6.7). Of these patients, 89 (34%) were subsequently diagnosed with PCa including 21 (8%) with high-grade PCa. Pre-biopsy PSA was higher among patients subsequently diagnosed with (6.7 vs 5.8, P<0.001). Of those diagnosed with subsequent PCa, 69/89 (78%) had less than or equal to Gleason 3+3 disease and only 15/89 (17%) had Gleason 7 and 6/89 (6%) revealed Gleason ?8-10. Radical prostatectomy was performed on 36/89 (40%) patients. Surgical pathology revealed 11 patients ?Gleason 8-10 PCa. CONCLUSIONS: Although 34% of patients with an initial diagnosis of ASAP who had repeat biopsy were subsequently diagnosed with PCa only, only 22% (8% of the total cohort) were found to have high-grade disease. Higher PSA was associated with increased risk of identifying PCa on repeat biopsy. These findings suggest that immediate repeat biopsy may be omitted in the majority of men with ASAP. PMID- 26857146 TI - The influence of prednisone on the efficacy of docetaxel in men with metastatic castration-resistant prostate cancer. AB - BACKGROUND: Prednisone and other corticosteroids can provide palliation and tumor responses in patients with prostate cancer. The combination of docetaxel and prednisone was the first treatment shown to prolong survival in men with metastatic castration-resistant prostate cancer (mCRPC). Since the approval of docetaxel in 2004, additional treatments are available, including abiraterone, which is also administered with prednisone. Therefore, patients are increasingly likely to have prednisone therapy several times throughout their disease course, and the contribution of prednisone to the efficacy of docetaxel is unknown. METHODS: We conducted a retrospective study of patients with mCPRC treated with docetaxel at our institution between 2004 and 2014. Patients were divided into two cohorts based upon whether prednisone was co-administered with docetaxel. Cohorts were further stratified based upon prior prednisone (with abiraterone) or hydrocortisone (with ketoconazole) use. The primary end point was clinical/radiographic progression-free survival (PFS). The secondary end points were >50% PSA response rate and PSA progression-free survival (PSA PFS). A multivariable Cox regression model was constructed to determine whether prednisone use was independently predictive of PFS. RESULTS: We identified 200 consecutive patients for inclusion in the study: 131 men received docetaxel with prednisone and 69 received docetaxel alone. The docetaxel-prednisone cohort had superior PFS compared with the docetaxel-alone cohort (median PFS: 7.8 vs. 6.2 months, HR 0.68 (95% confidence interval (CI) 0.48-0.97), P=0.03). Prednisone use was associated with a reduced risk of progression on docetaxel in the propensity score-weighted multivariable Cox model (P=0.002). Among abiraterone- or ketoconazole-pretreated patients, no difference in PFS was observed between prednisone-containing and non-prednisone-containing docetaxel regimens (median PFS: 7.1 vs. 6.3 months, HR 0.96 (95% CI 0.59-1.57), P=0.87). CONCLUSIONS: The incorporation of prednisone potentially augments the efficacy of docetaxel in patients with mCRPC. We hypothesize that this advantage is limited to patients who have not previously received corticosteroids. Prospective confirmation is needed. PMID- 26857147 TI - Pyruvate dehydrogenase B promoted the growth and migration of the nasopharyngeal carcinoma cells. AB - Metabolism alteration is one of the hallmarks of cancer cells. Although several studies have demonstrated that glycolysis played important roles in the progression of nasopharyngeal carcinoma (NPC), the functions of specific metabolism-associated genes remain largely unknown. In this study, it was found that Pyruvate dehydrogenase B (PDHB), which catalyzed the conversion of pyruvate to Acetyl-CoA, was downregulated in NPC cells. Forced expression of PDHB in NPC cells inhibited cell growth and migration, while knocking down the expression of PDHB promoted the growth, migration, and tumorigenesis of NPC cells. Mechanism study showed that PDHB inhibited ERK signaling and cell growth driven by RasV12. Collectively, our study demonstrated the suppressive roles of PDHB in the progression of NPC, and restoring the function of PDHB might be a promising strategy for NPC therapy. PMID- 26857148 TI - Differences in Prostate-Specific Antigen Testing Among Urologists and Primary Care Physicians Following the 2012 USPSTF Recommendations. PMID- 26857149 TI - Update on Provisional Technique for Bifurcation Interventions. AB - A series of scientific evidence supports the concept that provisional side-branch stenting should be the preferred strategy for percutaneous coronary intervention of bifurcation coronary lesions. However, to date, many interventional cardiologists still consider this technique unsuitable for complex bifurcation lesions. This is mainly due to the fact that provisional stenting may be performed in different ways and several technical refinements may influence the procedural outcome. We here systematically overviewed the arguments which should be considered during the following steps of the provisional strategy: branch wiring, side-branch predilation, "crossover" stenting, proximal optimization, kissing balloon and the side-branch rescue techniques. We suggest that provisional stenting should be regarded as a highly flexible technique which, with specific technical tricks, may allow us to safely treat patients with wide spectrum of bifurcated lesion complexity. PMID- 26857152 TI - Stepwise isolation of an unprecedented silylene supported dinuclear gold(i) cation with aurophilic interaction. AB - The silylene (PhC(NtBu)2SiN(PPh2)(2,6-iPr2-C6H3)) (2) was prepared from the previously reported (PhC(NtBu)2SiCl) salt elimination method. The reaction of 2 with AuCl(SMe2) afforded [(PhC(NtBu)2SiN(PPh2)(2,6-iPr2-C6H3))AuCl] (3). Note here that only Si(ii) is coordinated to Au(i), while P(iii) remains uncoordinated. The higher negative value of the electrostatic potential (ESP) at the Si-centre (-28.8 kcal mol(-1)) as compared to that at the P-centre (-15.3 kcal mol(-1)) justifies this observation. Furthermore, the chloride abstraction from 3 by AgSbF6 led to the formation of a dinuclear Au(i) cationic complex, [PhC(NtBu)2Si(2,6-iPr2-C6H3NPPh2)(Au)]2[SbF6]2 (4), which displays an intra molecular Au...Au interaction of 2.865 A. PMID- 26857151 TI - New Studies Do Not Challenge the American College of Cardiology/American Heart Association Lipid Guidelines. PMID- 26857150 TI - Functional transcription factor target discovery via compendia of binding and expression profiles. AB - Genome-wide experiments to map the DNA-binding locations of transcription associated factors (TFs) have shown that the number of genes bound by a TF far exceeds the number of possible direct target genes. Distinguishing functional from non-functional binding is therefore a major challenge in the study of transcriptional regulation. We hypothesized that functional targets can be discovered by correlating binding and expression profiles across multiple experimental conditions. To test this hypothesis, we obtained ChIP-seq and RNA seq data from matching cell types from the human ENCODE resource, considered promoter-proximal and distal cumulative regulatory models to map binding sites to genes, and used a combination of linear and non-linear measures to correlate binding and expression data. We found that a high degree of correlation between a gene's TF-binding and expression profiles was significantly more predictive of the gene being differentially expressed upon knockdown of that TF, compared to using binding sites in the cell type of interest only. Remarkably, TF targets predicted from correlation across a compendium of cell types were also predictive of functional targets in other cell types. Finally, correlation across a time course of ChIP-seq and RNA-seq experiments was also predictive of functional TF targets in that tissue. PMID- 26857153 TI - Specific cell surface labeling of GPCRs using split GFP. AB - Specific cell surface labeling is essential for visualizing the internalization processes of G-protein coupled receptors (GPCRs) and for gaining mechanistic insight of GPCR functions. Here we present a rapid, specific, and versatile labeling scheme for GPCRs at living-cell membrane with the use of a split green fluorescent protein (GFP). Demonstrated with two GPCRs, GPR17 and CysLT2R, we show that two beta-stands (beta-stands 10 and 11) derived from a superfolder GFP (sfGFP) can be engineered to one of the three extracellular loop of a GPCR. The complementary fragment of sfGFP has nine beta-strands (beta-stands 1-9) that carries the mature fluorophore, and can be proteolytically derived from the full length sfGFP. Separately the GFP fragments are non-fluorescent, but become fluorescent upon assembly, thus allowing specific labeling of the target proteins. The two GFP fragments rapidly assemble and the resulting complex is extremely tight under non-denaturing conditions, which allows real-time and quantitative assessment of the internalized GPCRs. We envision that this labeling scheme will be of great use for labeling other membrane proteins in various biological and pharmacological applications. PMID- 26857154 TI - Leukemic mastopathy. PMID- 26857156 TI - Contributors to dietary glycaemic index and glycaemic load in the Netherlands: the role of beer. AB - Diets high in glycaemic index (GI) and glycaemic load (GL) have been associated with a higher diabetes risk. Beer explained a large proportion of variation in GI in a Finnish and an American study. However, few beers have been tested according to International Organization for Standardization (ISO) methodology. We tested the GI of beer and estimated its contribution to dietary GI and GL in the Netherlands. GI testing of pilsner beer (Pilsner Urquell) was conducted at The University of Sydney according to ISO international standards with glucose as the reference food. Subsequently, GI and GL values were assigned to 2556 food items in the 2011 Dutch food composition table using a six-step methodology and consulting four databases. This table was linked to dietary data from 2106 adults in the Dutch National Food Consumption Survey 2007-2010. Stepwise linear regression identified contribution to inter-individual variation in dietary GI and GL. The GI of pilsner beer was 89 (SD 5). Beer consumption contributed to 9.6 and 5.3% inter-individual variation in GI and GL, respectively. Other foods that contributed to the inter-individual variation in GI and GL included potatoes, bread, soft drinks, sugar, candy, wine, coffee and tea. The results were more pronounced in men than in women. In conclusion, beer is a high-GI food. Despite its relatively low carbohydrate content (approximately 4-5 g/100 ml), it still made a contribution to dietary GL, especially in men. Next to potatoes, bread, sugar and sugar-sweetened beverages, beer captured a considerable proportion of between-person variability in GI and GL in the Dutch diet. PMID- 26857157 TI - Carcass traits and meat quality of Nellore cattle fed different non-fiber carbohydrates sources associated with crude glycerin. AB - Crude glycerin, a potential energy source for ruminant animals, has been evaluated, mainly, in diets with high starch content. However, a limit number of studies have evaluated the inclusion of crude glycerin in low starch diets. This study aimed to evaluate the effects of the association of crude glycerin with corn grain or citrus pulp on carcass traits and meat quality of Nellore bulls (n=30, 402+/-31 kg initial weight). The treatment consisted of: CON=control, without crude glycerin; CG10=10% of crude glycerin and corn grain; CG15=15% of crude glycerin and corn grain; CP10=10% of crude glycerin and citrus pulp; CP15=15% of crude glycerin and citrus pulp. The performance parameters and carcass traits were not affected by treatments (P>0.05). The inclusion of crude glycerin decreased yellow color intensity and increased fatty acids pentadecanoic and heptadecenoic in meat (P<0.05), without affecting neither the concentration of polyunsaturated fatty acids nor the relationship of saturated and unsaturated fatty acids. The association of crude glycerin with corn or citrus pulp has no adverse effects on carcass characteristics and meat quality. PMID- 26857155 TI - Pregnancy outcomes of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab: a Japanese experience and updated review. AB - Pregnancy with paroxysmal nocturnal hemoglobinuria (PNH) is associated with significant risk of complications, such as life-threatening thrombosis. Recently, eculizumab has come into clinical use and revolutionized the treatment of PNH. However, clinical information regarding eculizumab use for PNH during pregnancy is limited. The present report describes pregnancies with PNH treated with eculizumab that were registered with the Japan PNH study group and reviews the literature. In case 1, the patient received eculizumab throughout pregnancy and delivered a healthy neonate at term, although breakthrough hemolysis occurred at 20 weeks of gestation. In case 2, the patient discontinued eculizumab before pregnancy and developed preeclampsia at 27 weeks of gestation. She received eculizumab and delivered a preterm, but healthy, neonate by cesarean section. In case 3, the patient received eculizumab from 18 weeks of gestation and delivered a healthy neonate at term without any complications. Reports of 11 pregnant women treated with eculizumab were identified in the literature. Of 14 pregnancies, including our own cases, breakthrough hemolysis and preeclampsia occurred in five and two cases, respectively. There were no thrombotic complications, maternal or neonatal deaths, or fetal structural abnormalities. Thus, eculizumab appears to be safe and effective for managing PNH during pregnancy. PMID- 26857159 TI - Synthesis of activated 3'-amino-3'-deoxy-2-thio-thymidine, a superior substrate for the nonenzymatic copying of nucleic acid templates. AB - We present a scalable synthesis of 3'-amino-3'-deoxy-2-thio-thymidine-5' phosphoro-2-methylimidazolide, an activated monomer that can copy adenosine residues in nucleic acid templates rapidly without a polymerase. The sulfur atom substitution enhances the rate of template copying by 5-fold compared with the 3' amino-3'-deoxy-T monomer, while the 3'-amino monomers exhibit a 2- to 30-fold enhancement compared with their ribonucleotide counterparts. PMID- 26857158 TI - Tracing amino acid exchange during host-pathogen interaction by combined stable isotope time-resolved Raman spectral imaging. AB - This study investigates the temporal and spatial interchange of the aromatic amino acid phenylalanine (Phe) between human retinal pigment epithelial cell line (ARPE-19) and tachyzoites of the apicomplexan protozoan parasite Toxoplasma gondii (T. gondii). Stable isotope labelling by amino acids in cell culture (SILAC) is combined with Raman micro-spectroscopy to selectively monitor the incorporation of deuterium-labelled Phe into proteins in individual live tachyzoites. Our results show a very rapid uptake of l-Phe(D8) by the intracellular growing parasite. T. gondii tachyzoites are capable of extracting l Phe(D8) from host cells as soon as it invades the cell. l-Phe(D8) from the host cell completely replaces the l-Phe within T. gondii tachyzoites 7-9 hours after infection. A quantitative model based on Raman spectra allowed an estimation of the exchange rate of Phe as 0.5-1.6 * 10(4) molecules/s. On the other hand, extracellular tachyzoites were not able to consume l-Phe(D8) after 24 hours of infection. These findings further our understanding of the amino acid trafficking between host cells and this strictly intracellular parasite. In particular, this study highlights new aspects of the metabolism of amino acid Phe operative during the interaction between T. gondii and its host cell. PMID- 26857160 TI - Trajectories of total depression and depressive symptoms in prostate cancer patients receiving six months of hormone therapy. AB - OBJECTIVE: The aim of this study was to investigate the effects of hormone therapy (HT) on depression and depressive symptoms in prostate cancer patients undergoing 6 months of HT. METHODS: One hundred two prostate cancer patients who had been prescribed HT completed the Zung Self-rating Depression Scale (SDS) and two questions about their sexual enjoyment and performance, plus a background questionnaire before HT, after 8 to 10 weeks of HT and again after 16 to 20 weeks of HT. RESULTS: There was a significant increase in SDS scores from before to during HT. High depression score before HT was a significant predictor of later increases in depression during HT. Increases in depressive symptoms were restricted to 8 of the 20 SDS symptoms, the most powerful change being in sexual anhedonia, which was a result of decreased ability to perform during sexual activity. CONCLUSIONS: The association between HT and elevated depression is confirmed, but the relative influence of sexual anhedonia over other depressive symptoms expands the understanding of this association. The effects of decreased ability to perform during sex appear to dominate the increase in depression during HT. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26857162 TI - Effect of Obstructive Sleep Apnea in Acute Coronary Syndrome. AB - The effect of obstructive sleep apnea (OSA) on clinical outcomes after acute coronary syndrome (ACS) is incompletely defined. We sought to determine the prevalence of OSA in patients with ACS and evaluate prognostic impact of OSA and continuous positive airway pressure (CPAP) therapy in these patients. This was a prospective longitudinal cohort study of 73 patients admitted on cardiac intensive care unit for ACS. Cardiorespiratory sleep study and/or polysomnography were performed in all patients. CPAP was recommended if Apnea-Hypopnea Index >=5. The main study outcome was a composite of death for any cause, myocardial infarction, and myocardial revascularization. OSA was diagnosed in 46 patients (63%). Age and cardiovascular risk factors were not significantly different between groups. OSA was classified as mild (m-OSA) in 14 patients (30%) and as moderate-to-severe (s-OSA) in 32 patients (70%). After a median follow-up of 75 months (interquartile range 71 to 79), patients with s-OSA had lower event-free survival rate. After adjustment for gender, patients with s-OSA showed a significantly higher incidence of the composite end point (hazard ratio 3.58, 95% CI 1.09 to 17.73, p = 0.035). Adherence to CPAP occurred in 19 patients (41%), but compliance to CPAP therapy did not reduce the risk of composite end point (hazard ratio 0.87, 95% CI 0.31 to 2.46, p = 0.798). In conclusion, OSA is an underdiagnosed disease with high prevalence in patients with ACS. It is urgent to establish screening protocols because those have high diagnostic yield and allow identifying a group of patients with manifestly unfavorable prognosis. PMID- 26857161 TI - Comparison of Risk of Atrial Fibrillation in Black Versus White Patients After Coronary Artery Bypass Grafting. AB - Obesity has been identified as a risk factor for postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG). However, no studies have addressed the influence of race on this association. A total of 13,594 patients undergoing first-time, isolated CABG without preoperative AF between 1992 and 2011 were included in our study. The association between body mass index and POAF was compared by race. Relative risk and 95% CIs were computed using maximum likelihood log-binomial regression. Increasing levels of body mass index were associated with higher POAF risk after CABG in black but not white patients (pinteraction = 0.0009). PMID- 26857163 TI - Comparison of Left Ventricular Volume and Ejection Fraction and Frequency and Extent of Aortic Regurgitation After Operative Repair of Type A Aortic Dissection Among Three Different Surgical Techniques. AB - Differences in recurrence rate of aortic regurgitation (AR) and extent of left ventricular (LV) remodeling across the different surgical options in patients operated for type A aortic dissection remain unknown. The present evaluation compared the AR recurrence rate and changes in LV volumes and systolic function in valve-sparing aorta replacement (VSAR), supracoronary ascending aorta replacement (SCAR), and aortic valve and aorta replacement (AVAR). A total of 97 patients (58 +/- 12 years, 62% men) with acute type A aortic dissection who underwent VSAR (n = 24), SCAR (n = 43), or AVAR (n = 30) were evaluated. Changes in LV volumes and function between postoperative and follow-up were compared using linear mixed models. Postoperative AR grades were not significantly different between groups. However, after median follow-up of 47 months, AR grade >=2 was significantly more often observed in SCAR (55%) and VSAR (25%) compared to AVAR (0%, p <0.001). LV volumes remained stable in VSAR and AVAR but increased significantly in SCAR (LV end-diastolic volume: from 99 +/- 4 to 131 +/- 6 ml; p <0.001; LV end-systolic volume: from 49 +/- 3 to 66 +/- 5 ml; p = 0.002). In patients with recurrent AR grade >=2 at follow-up, LV volumes increased, whereas patients without recurrent AR did not show significant LV dilatation. In conclusion, patients with acute type A aortic dissection who underwent SCAR or VSAR showed more frequently AR grade >=2 recurrence compared to AVAR. However, only patients who underwent SCAR experienced adverse LV remodeling at follow-up. Recurrence of AR grade >=2 was associated with adverse LV remodeling. PMID- 26857164 TI - Comparison of the Global Registry of Acute Coronary Events Risk Score Versus the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse outcomes With Early Implementation of the ACC/AHA Guidelines Risk Score to Predict In-Hospital Mortality and Major Bleeding in Acute Coronary Syndromes. AB - Risk assessment plays a major role in the management of acute coronary syndrome. The aim was to compare the performance of the Global Registry of Acute Coronary Events (GRACE) and the Can Rapid risk stratification of Unstable angina patients Suppress Adverse outcomes with Early implementation of the American College of Cardiology/American Heart Asociation guidelines (CRUSADE) risk scores to predict in-hospital mortality and major bleeding (MB) in 1,587 consecutive patients with acute coronary syndrome. In-hospital deaths and bleeding complications were prospectively collected. Bleeding complications were defined according to CRUSADE and Bleeding Academic Research Consortium (BARC) criteria. During the hospitalization, 71 patients (4.5%) died, 37 patients (2.3%) had BARC MB and 34 patients (2.1%) had CRUSADE MB. Receiver operating characteristic curves analyses showed GRACE risk score has better discrimination capacity than CRUSADE risk score for both, mortality (0.86 vs 0.79; p = 0.018) and BARC MB (0.80 vs 0.73; p = 0.028), but similar for CRUSADE MB (0.79 vs 0.79; p = 0.921). Both scores had low discrimination for predicting MB in the elderly (>75 years) and patients with atrial fibrillation, whereas CRUSADE risk score was especially poor for predicting MB in patients with <60 ml/min/1.73 m(2) or those treated with new antiplatelets. Reclassification analyses showed GRACE risk score was associated with a significant improvement in the predictive accuracy of CRUSADE risk score for predicting mortality (net reclassification improvement: 22.5%; p <0.001) and MB (net reclassification improvement: 17.6%; p = 0.033) but not for CRUSADE MB. In conclusion, GRACE risk score has a better predictive performance for predicting both in-hospital mortality and BARC MB. In light of these findings, we propose the GRACE score as a single score to predict these in-hospital complications. PMID- 26857165 TI - Relation of Internal Elastic Lamellar Layer Disruption to Neointimal Cellular Proliferation and Type III Collagen Deposition in Human Peripheral Artery Restenosis. AB - Smooth muscle cell proliferation and extracellular matrix formation are responsible for disease progression in de novo and restenotic atherosclerosis. Internal elastic lamella (IEL) layer maintains the structural integrity of intima, and disruption of IEL may be associated with alterations in neointima, type III collagen deposition, and lesion progression in restenosis. Nineteen restenotic plaques (12 patients) procured during peripheral interventions were compared with 13 control plaques (12 patients) without restenosis. Hematoxylin & Eosin and elastic trichrome stains were used to measure length and percentage of IEL disruption, cellularity, and inflammation score. Type I and III collagens, smooth muscle cell (smc), fibroblast density, and nuclear proliferation (Ki67) percentage were evaluated by immunohistochemistry. IEL disruption percentage (28 +/- 3.6 vs 6.1 +/- 2.4; p = 0.0006), type III collagen content (0.33 +/- 0.06 vs 0.17 +/- 0.07; p = 0.0001), smc density (2014 +/- 120 vs 923 +/- 150; p = 0.0001), fibroblast density (2,282 +/- 297 vs 906 +/- 138; p = 0.0001), and Ki67 percentage (21.6 +/- 2 vs 8.2 +/- 0.65; p = 0.0001) were significantly increased in restenotic plaques compared to de novo plaques. Logistic regression analysis identified significant correlation between IEL disruption and neointimal smc density (r = 0.45; p = 0.01) and with type III collagen deposition (r = 0.61; p = 0.02) in restenosis. Increased IEL disruption may trigger cellular proliferation, altering collagen production, and enhancing restenotic neointima. In conclusion, understanding the pathologic and molecular basis of restenosis and meticulous guided interventions oriented to minimize IEL damage may aid to reduce neointimal proliferation and the occurrence of restenosis. PMID- 26857166 TI - Formula G1: Cell cycle in the driver's seat of stem cell fate determination. AB - Cell cycle dynamics has emerged as a key regulator of stem cell fate decisions. In particular, differentiation decisions are associated with the G1 phase, and recent evidence suggests that self-renewal is actively regulated outside of G1. The mechanisms underlying these phenomena are largely unknown, but direct control of gene regulatory programs by the cell cycle machinery is heavily implicated. A recent study sheds important mechanistic insight by demonstrating that in human embryonic stem cells (hESCs) the Cyclin-dependent kinase CDK2 controls a wide spread epigenetic program that drives transcription at differentiation-related gene promoters specifically in G1. Here, we discuss this finding and explore whether similar mechanisms are likely to function in multipotent stem cells. The implications of this discovery toward our understanding of stem cell-related disease are discussed, and we postulate novel mechanisms that position the cell cycle as a regulator of cell fate gene networks at epigenetic, transcriptional and post-transcriptional levels. PMID- 26857167 TI - Are Tertiary Care Paediatricians Prepared for Disaster Situations? AB - INTRODUCTION: Children, with their specific vulnerabilities and needs, make up to more than 20% of society, so they are at risk of getting involved in disasters. Are the specialists treating them for medical problems in daily life also capable to deal with them in disaster situations? HYPOTHESIS/PROBLEM: The goals of this study were to evaluate perceived knowledge and capability of tertiary pediatricians to deal with disasters, to identify promoting factors, and to evaluate education need and willingness to work. METHODS: A survey looking for demographics, hospital disaster planning, estimated risk and capability for disasters, training, and willingness to work, and a set of six content assessment questions to evaluate knowledge, were presented to emergency pediatricians and pediatric emergency physicians in specialized tertiary centers. RESULTS: The response rate was 51%. Thirty-five percent had disaster training and 53% felt that disaster education should be obligatory in their curriculum. Risk for disasters was estimated from 2.4/10 for nuclear incidents to 7.6/10 for major trauma. Self-estimated capability for these situations ranged from 1.8/10 in nuclear incidents to 7.6/10 in major trauma. Unconditional willingness to work ranged from 37% in nuclear situations to 68% in pandemics. Mean score on the questions was 2.06/6. Training, knowledge of antidote and personal protective equipment (PPE) use, self-estimated capability, and exposure were significant predictors for higher scores. Willingness to work correlated significantly with age, self-estimated capability, and risk estimation. In case of chemical and nuclear incidents, there was correlation with knowledge on the use of decontamination, PPE, and radio-detection devices. CONCLUSION: Despite a clear perception of the risks and a high willingness to work, preparedness is limited. The major conclusion is that basics of disaster management should be included in pediatric training. PMID- 26857168 TI - Perpetuation theory and the racial segregation of young adults. AB - Previous research confirms a strong empirical association between the racial composition of young adults' residential areas and the racial compositions of the residential areas and schools of their youth. Perpetuation theory predicts that part of this association is causal. The present study uses data from the National Education Longitudinal Study (NELS) and the U.S. Censuses of 1990 and 2000 to test for this effect with regression models, propensity-score-weighted models with robustness tests, and regression models that look at long-distance movers. The findings suggest that the association declines rapidly as the distance moved increases, but it remains robust even at long distances. It is also stronger for African Americans and more assimilated Latinos than for whites and less assimilated Latinos. These findings suggests that to some extent, young white, African American, and Latino adults are residentially segregated from each other because they grew up that way. Policies that promote integrating youth residentially and/or desegregating schools may contribute to residential integration over time. PMID- 26857169 TI - The stigma of mental illness in the labor market. AB - Mental illness labels are accompanied by devaluation and discrimination. We extend research on reactions to mental illness by utilizing a field experiment (N = 635) to test effects of mental illness labels on labor market discrimination. This study involved sending fictitious applications to job listings, some applications indicating a history of mental illness and some indicating a history of physical injury. In line with research indicating that mental illness leads to stigma, we predicted fewer callbacks to candidates with mental illness. We also predicted relatively fewer callbacks for applicants with mental illness when the jobs involved a greater likelihood for interpersonal contact with the employer. Results showed significant discrimination against applicants with mental illness, but did not indicate an effect of potential proximity to the employer. This contributes a valuable finding in a natural setting to research on labor market discrimination towards people with mental illness. PMID- 26857170 TI - The human dimensions of climate change: A micro-level assessment of views from the ecological modernization, political economy and human ecology perspectives. AB - Understanding the manifold human and physical dimensions of climate change has become an area of great interest to researchers in recent decades. Using a U.S. nationally-representative data set and drawing on the ecological modernization, political economy, and human ecology perspectives, this study examines the impacts of energy efficiency technologies, affluence, household demographics, and biophysical characteristics on residential CO2 emissions. Overall, the study provides mixed support for the ecological modernization perspective. While several findings are consistent with the theory's expectation that modern societies can harness technology to mitigate human impacts on the environment, others directly contradict it. Also, the theory's prediction of an inverted U shaped relationship between affluence and environmental impacts is contradicted. The evidence is somewhat more supportive of the political economy and human ecology perspectives, with affluence, some indicators of technology, household demographics, and biophysical characteristics emerging as important drivers of residential CO2 emissions. PMID- 26857171 TI - 'It's The Sun Wot Won It': Evidence of media influence on political attitudes and voting from a UK quasi-natural experiment. AB - Do print media significantly impact political attitudes and party identification? To examine this question, we draw on a rare quasi-natural experiment that occurred when The Sun, a right-leaning UK tabloid, shifted its support to the Labour party in 1997 and back to the Conservative party in 2010. We compared changes in party identification and political attitudes among Sun readers with non-readers and other newspaper readerships. We find that The Sun's endorsements were associated with a significant increase in readers' support for Labour in 1997, approximately 525,000 votes, and its switch back was associated with about 550,000 extra votes for the Conservatives in 2010. Although we observed changes in readers' party preference, there was no effect on underlying political preferences. The magnitude of these changes, about 2% of the popular vote, would have been unable to alter the outcome of the 1997 General Election, but may have affected the 2010 Election. PMID- 26857172 TI - Peer influence on protest participation: Communication and trust between co workers as inhibitors or facilitators of mobilization. AB - In this article, we investigate how communication and trust networks between employees affect participation in a strike. We analyze whether the strength of network relations is related to congruence in strike behavior using social network data on 59 Dutch workers. We find that private communication networks and trust networks lead to similar strike behavior. This finding indicates that networks not only promote protest mobilization but are also vehicles for demobilization, albeit through different network relations. PMID- 26857173 TI - Educational trajectories and inequalities of political engagement among adolescents in England. AB - Through analysing longitudinal data this article explores the effect of education trajectories between the ages 14-19 on voting and protesting at age 20 taking into account both type of education (vocational/academic) and level of qualifications (Levels 1-3). We find that these trajectories exert an independent effect on both outcomes. Gaining low level qualifications (up to Level 2) and in particular low level vocational qualifications diminishes the chances of political participation relative to Level 3 and academic qualifications. Whilst a wider range of qualifications are conducive to voting, only Level 3 academic qualifications support protesting relative to other qualifications. Post-14 education thus seems to make protesting more of an elite affair. Considering that the vast majority of students in the vocational and lower-level pathways come from low SES families, the undermining influence of these pathways on political participation will be felt disproportionally among the group of socially disadvantaged students. PMID- 26857174 TI - Macro-conditions and immigrants' happiness: Is moving to a wealthy country all that matters? AB - Migrants look for a better life. In what kind of country will they live happiest? Many migrants aspire to move to wealthy countries, but non-economic factors might be important as well in making a country livable for migrants. This issue is addressed here by examining the impact of macroeconomic conditions and non economic macro-conditions (good governance and a pleasant social climate) on immigrants' happiness in twenty European nations. We find that immigrants' happiness depends both on economic and non-economic macro-conditions. The social climate is especially important, particularly in terms of a positive attitude in society towards migrants. Our findings imply that the choice of destination country matters for migrants' happiness and that the discrepancy between migration motives and migration outcomes may constrain immigrants from maximizing subjective gains via migration. PMID- 26857175 TI - Using geocoded survey data to improve the accuracy of multilevel small area synthetic estimates. AB - This paper examines the secondary data requirements for multilevel small area synthetic estimation (ML-SASE). This research method uses secondary survey data sets as source data for statistical models. The parameters of these models are used to generate data for small areas. The paper assesses the impact of knowing the geographical location of survey respondents on the accuracy of estimates, moving beyond debating the generic merits of geocoded social survey datasets to examine quantitatively the hypothesis that knowing the approximate location of respondents can improve the accuracy of the resultant estimates. Four sets of synthetic estimates are generated to predict expected levels of limiting long term illnesses using different levels of knowledge about respondent location. The estimates were compared to comprehensive census data on limiting long term illness (LLTI). Estimates based on fully geocoded data were more accurate than estimates based on data that did not include geocodes. PMID- 26857176 TI - Preferences, constraints, and the process of sex segregation in college majors: A choice analysis. AB - The persistence of horizontal sex segregation in higher education continues to puzzle social scientists. To help resolve this puzzle, we analyze a sample of college entrants in Germany with a discrete choice design that allows for social learning from the experiences of others. We make at least two contributions to the state of research. First, we test whether essentialist gender stereotypes affect major selection mostly through internalization or rather as external constraints that high school graduates adapt their behavior to. Empirically, we find that internalized vocational interests better explain gendered major choices than conformance with friends' and parents' expectations does. Second, we scrutinize whether segregation results from women's anticipation of gendered family roles or from their anticipation of sex-based discrimination, but we find no evidence for either of these hypotheses. As in most previous studies, differences in mathematics achievement fail to explain gendered patterns of selection into college majors. PMID- 26857177 TI - Discovering complex interrelationships between socioeconomic status and health in Europe: A case study applying Bayesian Networks. AB - Studies assume that socioeconomic status determines individuals' states of health, but how does health determine socioeconomic status? And how does this association vary depending on contextual differences? To answer this question, our study uses an additive Bayesian Networks model to explain the interrelationships between health and socioeconomic determinants using complex and messy data. This model has been used to find the most probable structure in a network to describe the interdependence of these factors in five European welfare state regimes. The advantage of this study is that it offers a specific picture to describe the complex interrelationship between socioeconomic determinants and health, producing a network that is controlled by socio-demographic factors such as gender and age. The present work provides a general framework to describe and understand the complex association between socioeconomic determinants and health. PMID- 26857178 TI - Preventing Congenital Cytomegalovirus Infection: Protection to a 'T'. AB - A lack of knowledge about the correlates of maternal immunity required for protection of the placenta and fetus against congenital cytomegalovirus (CMV) transmission has complicated vaccine development. New work from Bialas and colleagues demonstrates a critical role for maternal CD4(+) T cells in controlling viremia and preventing CMV-associated fetal disease. PMID- 26857179 TI - Osteomyelitis caused by Veillonella species: Case report and review of the literature. AB - Previously, Veillonella species had been considered as nonpathogenic and rarely caused serious infections. We report a case of 25-year-old man with osteomyelitis caused by Veillonella species. He was admitted to the hospital due to an open fracture to the left radial bone caused by industrial washing machine accident, and emergency surgery was performed. However, wound infections occurred one week after the operation. Although Acinetobacter baumannii and Serratia marcescens were cultured from the pus, obligate anaerobic bacteria were not detected at that point. Debridement was repeated and antibiotics were changed according to the result of bacterial culture and drug sensitivity. Despite this, the infection was poorly controlled. On the 5th debridement, granulomatous bone tissues on pseudarthrosis were found for the first time at the infection site. Although no bacteria was detected with aerobic culture, anaerobic incubation revealed Gram negative cocci which was later identified as Veillonella species by 16S rRNA gene sequence analysis. His condition improved without any additional debridement after adding effective antibiotics against Veillonella species. It is well known that prolonged infection with aerobes consumes oxygen in the infection site and leads the environment to more favorable conditions for anaerobic bacteria, thus we speculated that prolonged infection with bacteria such as S. marcescens induced the favorable environment for Veillonella species. Physicians should realize the importance of anaerobic culture method in routine practice, especially in complicated cases such as the present case. In this article, we reviewed case reports of Veillonella infection and summarized the clinical features of this organism. PMID- 26857181 TI - 'Hero to Healing' drink-driving program for Indigenous communities in Far North Queensland. AB - Issue addressed Alcohol-related road crashes are a leading cause of the injury burden experienced by Indigenous Australians. Existing drink driving programs are primarily designed for the mainstream population. The 'Hero to Healing' program was specifically developed with Indigenous communities and is underpinned by the Community Reinforcement Approach (CRA). This paper reports on the formative evaluation of the program from delivery in two Far North Queensland communities. Methods Focus groups and semistructured interviews were conducted with drink driver participants (n=17) and other Elders and community members (n=8) after each program. Qualitative content analysis was used to categorise the transcripts. Results The CRA appealed to participants because of its flexible nature and encouragement of rearranging lifestyle factors, without specific focus on alcohol use. Participants readily identified with the social and peer-related risk and protective factors discussed. Cofacilitation of the program with Elders was identified as a key aspect of the program. More in-depth discussion about cannabis and driving, anger management skills and relationship issues are recommended. Conclusions Participants' recognition of content reinforced earlier project results, particularly the use of kinship pressure to motivate younger family members to drink drive. Study findings suggest that the principles of the CRA are useful; however, some amendments to the CRA components and program content were necessary. So what? Treating drink driving in regional and remote Indigenous Australian communities as a community and social issue, rather than an individual phenomenon, is likely to lead to a reduction in the number of road related injuries Indigenous people experience. PMID- 26857182 TI - A new dihydrobenzofuran lignan and potential alpha-glucosidase inhibitory activity of isolated compounds from Mitrephora teysmannii. AB - A new dihydrobenzofuran lignan, (2R,3S)-2-(3',4'-dimethoxyphenyl)-5-(3 hydroxypropyl)-7-methoxy-2,3-dihydrobenzofuran-3-methyl acetate, named as mitredrusin (1), was isolated from the leaves of Mitrephora teysmannii (Annonaceae) together with 12 known compounds including a related dihydrobenzofuran lignan: (-)-3',4-di-O-methylcedrusin (2), four polyacetylenic acids: 13(E)-octadecene-9,11-diynoic acid (3), 13(E),17-octadecadiene-9,11 diynoic acid (4), octadeca-9,11,13-triynoic acid (5) and octadeca-17-en-9,11,13 triynoic acid (6), five lignans: (-)-eudesmin (7), (-)-epieudesmin (8), (-) phillygenin (9), magnone A (10) and forsythialan B (11) and two megastigmans: (3S,5R,6S,7E,9R)-7-megastigmene-3,6,9-triol (12) and annoionol A (13). The chemical structures of these compounds were established on the basis of their 1-D and 2-D NMR spectroscopic data. All compounds were evaluated for their alpha glucosidase inhibitory activity. Among these isolates, polyacetylenic acids 3 and 4 showed more than 20-fold much higher activity compared with that of the antidiabetic drug acarbose. PMID- 26857180 TI - How credible are the study results? Evaluating and applying internal validity tools to literature-based assessments of environmental health hazards. AB - Environmental health hazard assessments are routinely relied upon for public health decision-making. The evidence base used in these assessments is typically developed from a collection of diverse sources of information of varying quality. It is critical that literature-based evaluations consider the credibility of individual studies used to reach conclusions through consistent, transparent and accepted methods. Systematic review procedures address study credibility by assessing internal validity or "risk of bias" - the assessment of whether the design and conduct of a study compromised the credibility of the link between exposure/intervention and outcome. This paper describes the commonalities and differences in risk-of-bias methods developed or used by five groups that conduct or provide methodological input for performing environmental health hazard assessments: the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group, the Navigation Guide, the National Toxicology Program's (NTP) Office of Health Assessment and Translation (OHAT) and Office of the Report on Carcinogens (ORoC), and the Integrated Risk Information System of the U.S. Environmental Protection Agency (EPA-IRIS). Each of these groups have been developing and applying rigorous assessment methods for integrating across a heterogeneous collection of human and animal studies to inform conclusions on potential environmental health hazards. There is substantial consistency across the groups in the consideration of risk-of-bias issues or "domains" for assessing observational human studies. There is a similar overlap in terms of domains addressed for animal studies; however, the groups differ in the relative emphasis placed on different aspects of risk of bias. Future directions for the continued harmonization and improvement of these methods are also discussed. PMID- 26857183 TI - Representations of epilepsy on the stage: From the Greeks to the 20th century. AB - Epilepsy is a disorder that has been used by dramatists in various ways over the ages and therefore highlights the views of the disorder as people saw it at the time the plays were written and performed. In the 6th century BC, links between tragedy and epilepsy were developed by Greek playwrights, especially Euripides, in Iphigenia among the Taureans and Heracles where epilepsy and madness associated with extreme violence occur together. Both Heracles and Orestes have episodes after a long period of physical exhaustion and nutritional deprivation. During the Renaissance, Shakespeare wrote plays featuring different neurological disorders, including epilepsy. Epilepsy plays a crucial part in the stories of Julius Caesar and Othello. Julius Caesar is a play about politics, and Caesar's epilepsy is used to illustrate his weakness and vulnerability which stigmatizes him and leads to his assassination. Othello is a play about jealousy, and Othello, an outsider, is stigmatized by his color, his weakness, and his 'seizures' as a form of demonic possession. In modern times, Night Mother portrays the hard life of Jessie, who lives with her mother. Jessie has no friends, her father has abandoned the family, and she has no privacy and is ashamed. Stigma and social pressures lead her to commit suicide. Henry James' novella, The Turn of the Screw, portrays a governess with dream-like states, deja vu, and loss of temporal awareness who has been sent to the country to look after two small children and ends up killing one. This novella was turned into an opera by Benjamin Britten. Most recently, performance art has been portraying epilepsy as the reality of a personally provoked seizure. Both Allan Sutherland and Rita Marcalo have purposely provoked themselves to have a seizure in front of an audience. They do this to show that seizures are just one disability. Whether this provokes stigma in audiences is unknown. Whether the performance artists understand the potential for status epilepticus has not been discussed. This article is part of a Special Issue entitled "Epilepsy, Art, and Creativity". PMID- 26857184 TI - Temperature-limited applications of mini-electrode catheter: authors' reply. PMID- 26857185 TI - Incidence of real-time recordings of pulmonary vein potentials using the third generation short-tip cryoballoon. AB - AIMS: The third-generation Cryoballoon Advance Short-tip (CB-ST) has been designed with a 40% shortened tip length compared with the former second generation CB Advance device. Ideally, a shorter tip should permit an improved visualization of real-time (RT) recordings in the pulmonary vein (PV) due to a more proximal positioning of the inner lumen mapping catheter. In the present study, we sought to analyse the rate of visualization of RT recordings in our first series of patients with the CB-ST device. METHODS AND RESULTS: All consecutive patients having undergone CB ablation using CB-ST technology were analysed. Exclusion criteria were the presence of an intracavitary thrombus, uncontrolled heart failure, moderate or severe valvular disease, and contraindications to general anaesthesia. A total of 60 consecutive patients (60.5 +/- 11.2 years, 62% males) were evaluated. Real-time recordings were detected in 209 of 240 PVs (87.1%). Specifically, RT recordings could be visualized in 55 left superior PVs (91.7%), 51 left inferior PVs (85.0%), 53 right superior PVs (88.3%), and 50 right inferior PVs (83.3). CONCLUSION: The rate of visualization of RT recordings is significantly high during third generation CB-ST ablation. Real-time recordings can be visualized in ~87.1% of veins with this novel cryoballoon. PMID- 26857186 TI - The contact force and continuity index parameters in pulmonary vein ablation: reply. PMID- 26857187 TI - Programmed ventricular stimulation early after myocardial infarction: are the guidelines right? PMID- 26857188 TI - Catheter ablation of atrial fibrillation in chronic heart failure: state-of-the art and future perspectives. AB - Catheter ablation of atrial fibrillation (AFCA) is a widely recommended treatment for symptomatic atrial fibrillation (AF) patients refractory to pharmacological treatment. Catheter ablation of AF is becoming a therapeutic option also among patients with chronic heart failure (CHF), on top of optimal medical treatment, being this arrhythmia related to a higher risk of death and/or symptom's worsening. In fact, in this setting, clinical evidences are continuously increasing. The present systematic review pools all published experiences concerning AFCA among CHF patients, or patients with structural cardiomyopathies, in order to summarize procedural safety and efficacy in this specific population. Moreover, the effects of AFCA on functional class and quality of life and the different procedural protocols available are discussed. The present work, therefore, attempts to provide an evidence-based clinical perspective to optimize clinical indication and tailor procedural characteristics and endpoints to patients affected by CHF referred for AFCA. PMID- 26857190 TI - The contact force and continuity index parameters in pulmonary vein ablation. PMID- 26857189 TI - Programmed ventricular stimulation early after myocardial infarction: authors' reply. PMID- 26857191 TI - Low risk of electromagnetic interference between smartphones and contemporary implantable cardioverter defibrillators. AB - AIMS: Manufacturers of implantable cardioverter defibrillators (ICDs) recommend that cell phones be maintained at a distance of ~15 cm from the implanted device in order to avoid risk of dysfunction due to electromagnetic interference (EMI). Data relating to this issue are outdated and do not reflect modern technology. Our aim was to evaluate whether EMI is still an issue with contemporary ICDs and smartphones. METHODS AND RESULTS: Consecutive patients implanted with a wireless enabled ICD were tested for potential interference with two models of recent 4G smartphones in conditions intended to maximize risk of EMI. A magnet effect (due to the phone speakers) was tested by placing the smartphones in the standby mode directly over the ICD generator. The presence of EMI artefacts on the real-time electrograms was evaluated by placing the smartphones in the standby, dialling, and operating modes directly over the generator casing and over the parasternal region in the vicinity of the ventricular lead. A total of 63 patients equipped with 29 different models of single, dual, or biventricular ICDs from five major manufacturers were included. None of the patients showed any evidence of interference with the smartphones during any of the 882 tests. CONCLUSION: The risk of EMI between modern smartphones and contemporary ICDs is low. This is probably due to the filters incorporated in the ICDs and low emission by the phones, as well as the small size of the magnets in the smartphones tested. STUDY REGISTRATION: NCT02330900 (http://www.clinicaltrials.gov). PMID- 26857192 TI - Importance of anatomy in cavotricuspid isthmus. PMID- 26857193 TI - Left persistent superior vena cava lead extraction using a femoral approach. PMID- 26857195 TI - ST2 Predicts Mortality and Length of Stay in a Critically Ill Noncardiac Intensive Care Unit Population. AB - OBJECTIVES: The biomarker suppression of tumorigenicity 2 (ST2) is a well established clinical biomarker of cardiac strain and is frequently elevated in a variety of cardiac conditions. Here, we sought to evaluate the prognostic value of ST2 in critically ill medical intensive care unit (MICU) patients without primary cardiac illness. METHODS: We measured ST2 and high-sensitivity troponin T (hsTnT) on plasma specimens collected on 441 patients following admission to a noncardiac MICU and evaluated the prognostic power of ST2 both alone and in multivariate models. RESULTS: Of these critically ill patients, 96% exhibited ST2 concentrations above the reference interval. ST2 concentrations were highly predictive of intensive care unit and hospital length of stay, as well as in hospital mortality, with high concentrations predicting a poor prognosis. Rates of in-hospital mortality were more than four times higher in patients with ST2 concentrations in the highest compared with the lowest quartile. In multivariate analysis, ST2 remained an important predictor of death after adjustment for age, hsTnT, and common diagnoses. CONCLUSIONS: ST2 is increased and predictive of prognosis in critically ill patients without primary cardiac disease, suggesting that critically ill patients may often have unrecognized cardiac injury. Clinical decision support algorithms incorporating ST2 and hsTnT results may be useful in patient risk stratification. PMID- 26857196 TI - Altered GABA neurotransmission in major depressive disorder: Re-analyzing publicly available data. PMID- 26857197 TI - Sleep duration, depression, and oxytocinergic genotype influence prepulse inhibition of the startle reflex in postpartum women. AB - The postpartum period is characterized by a post-withdrawal hormonal status, sleep deprivation, and susceptibility to affective disorders. Postpartum mothering involves automatic and attentional processes to screen out new external as well as internal stimuli. The present study investigated sensorimotor gating in relation to sleep duration, depression, as well as catecholaminergic and oxytocinergic genotypes in postpartum women. Prepulse inhibition (PPI) of the startle reflex and startle reactivity were assessed two months postpartum in 141 healthy and 29 depressed women. The catechol-O-methyltransferase (COMT) Val158Met, and oxytocin receptor (OXTR) rs237885 and rs53576 polymorphisms were genotyped, and data on sleep duration were collected. Short sleep duration (less than four hours in the preceding night) and postpartum depression were independently associated with lower PPI. Also, women with postpartum depression had higher startle reactivity in comparison with controls. The OXTR rs237885 genotype was related to PPI in an allele dose-dependent mode, with T/T healthy postpartum women carriers displaying the lowest PPI. Reduced sensorimotor gating was associated with sleep deprivation and depressive symptoms during the postpartum period. Individual neurophysiological vulnerability might be mediated by oxytocinergic genotype which relates to bonding and stress response. These findings implicate the putative relevance of lower PPI of the startle response as an objective physiological correlate of liability to postpartum depression. PMID- 26857198 TI - [Cardiopulmonary interactions in the course of mechanical ventilation]. AB - INTRODUCTION: The haemodynamic consequences of ventilation are multiple and complex and may affect all the determinants of cardiac performance such as heart rate, preload, contractility and afterload. These consequences affect both right and left ventricle and are also related to the biventricular interdependence. STATE-OF-THE-ART: Ventilation modifies the lung volume and also the intrathoracic pressure. Variations in lung volume have consequences on the pulmonary vascular resistance, hypoxic pulmonary vasoconstriction and ventricular interdependence. Variations in intrathoracic pressure have a major impact and affect systemic venous return, right ventricular preload, left ventricular preload, right ventricular afterload, left ventricular afterload and myocardial contracility. The haemodynamic consequences of positive pressure ventilation depend on the underlying chronic cardiopulmonary pathologies leading to the acute respiratory failure that was the indication for ventilation. CONCLUSION: In this review, we will focus on severe COPD exacerbation, acute left heart failure and weaning from ventilation. PMID- 26857199 TI - [The man who just wanted to quit smoking...]. PMID- 26857200 TI - [Cryptogenic organizing pneumonia]. AB - INTRODUCTION: Organizing pneumonia is a particular type of inflammatory reaction of the lung which gives rise to a clinico-pathological syndrome. It is called "secondary" when a cause such as an infection, a drug toxicity, or a connective tissue disease can be identified, or "cryptogenic" when no cause is identified. The clinical picture is usually characterized by the subacute onset of fever, fatigue, cough and dyspnea, with multiple subpleural areas of consolidation on thoracic imaging. STATE OF THE ART: Organizing pneumonia is characterised by the presence of buds of endoalveolar connective tissue. These result from an injury to the alveolar epithelium, followed by the deposition of fibrin in the alveolar spaces, and the migration of fibroblasts which produce a myxoid endoalveolar matrix. A remarkable feature of organizing pneumonia is the complete disappearance of these endoalveolar buds with corticosteroid treatment, in sharp contrast with what is seen in pulmonary fibrosis. The clinical response to corticosteroids is usually prompt and excellent. Relapses are frequent but usually benign. PERSPECTIVES AND CONCLUSION: As the clinical, imaging and pathological characteristics of organizing pneumonia are now well established, many questions remain unanswered, such as the mechanisms involved in the complete reversibility of the pulmonary lesions, and the role of steroid-sparing treatments such as immunomodulatory macrolides. PMID- 26857201 TI - Gender identity disorders and multiple sclerosis risk: A national record-linkage study. AB - BACKGROUND: An altered balance of gonadal hormones in males with gender identity disorders (GIDs) may increase multiple sclerosis (MS) risk both inherently and secondary to treatment in undergoing male-to-female conversion. OBJECTIVE: We investigated any association between GIDs and MS through analysis of record linked hospital statistics. METHOD: Analysis of English Hospital Episode Statistics, 1999-2012. RESULTS: The adjusted rate ratio (RR) of MS following GIDs in males was 6.63 (95% confidence interval (95% CI) = 1.81-17.01, p = 0.0002). The RR of MS following GIDs in females was 1.44 (95% CI = 0.47-3.37, p = 0.58). CONCLUSION: We report a strong association between GIDs and MS in male-to females, supporting a potential role for low testosterone and/or feminising hormones on MS risk in males. PMID- 26857202 TI - Oesophageal varices secondary to thrombosis of the superior vena cava due to jugular haemodialysis catheter. PMID- 26857203 TI - A rare cause of diarrhea in patients with focal segmental glomerulosclerosis. PMID- 26857204 TI - A membranous nephropathy case: Is it related to sulfasalazine? PMID- 26857205 TI - Case report of renal tubular acidosis and misdiagnosed. PMID- 26857206 TI - Anuria after renal graft biopsy: Multidisciplinary intervention. PMID- 26857207 TI - Rapid separation of polysaccharides using a novel spiral coil column by high speed countercurrent chromatography. AB - The separation of polysaccharides is time consuming. We developed and optimized a type-J counter-current chromatography system with a novel tri-rotor spiral coil column for the rapid separation of polysaccharides. The optimal composition of an aqueous PEG1000/K2 HPO4 /KH2 PO4 system was found to be 14:16:14 w/w/w where the lower phase was the mobile phase. Optimal performance was achieved at a column rotational speed, temperature, and flow rate of 1200 rpm, 45 degrees C, and 3.0 mL/min, respectively. The mobile phase was pumped from the inner terminal in a ''head-to-tail'' elution mode. Polysaccharide LCP-1 (10.7 mg) was successfully obtained in high purity in one step from 50.0 mg of a crude polysaccharide extracted from the lychee fruit (Litchi chinensis) within 100 min. LCP-1 possess a number-average molecular weight and weight-average molecular weight of 1.05 * 10(5) and 1.59 * 10(5) kDa, respectively. The monosaccharide composition consists of the molar ratio of glucose, galactose, and arabinose of 1.3:3.5:1. PMID- 26857208 TI - Blood Pressure Variability Provides Useful and Prognostic Information on the White-Coat Effect Among Older Patients. PMID- 26857209 TI - Metabolic improvement with fructose restriction: Is it the fructose or the weight loss? PMID- 26857210 TI - FoxO3 inactivation promotes human cholangiocarcinoma tumorigenesis and chemoresistance through Keap1-Nrf2 signaling. AB - FoxO transcription factors have been reported to play pivotal roles in tumorigenesis and drug resistance. The mechanisms underlying the tumor suppression function of FoxOs in human cancers remain largely unknown. Aberrant expression and activation of Nrf2 often correlate with chemoresistance and poor prognosis. Here, we report that FoxO3 directs the basal transcription of Kelch like ECH-associated protein 1 (Keap1), an adaptor protein that bridges Nrf2 to Cul3 for degradation. FoxO3 depletion resulted in Keap1 down-regulation, thereby activating Nrf2 signaling. We further demonstrated that inhibition of the FoxO3 Keap1 axis accounts for Nrf2 induction and activation induced by constitutively active AKT signaling or tumor necrosis factor alpha treatment. Unlike previous findings, FoxO3 silencing led to decreased reactive oxygen species production, therefore protecting cells from oxidative stress-induced killing in an Nrf2 dependent manner. Importantly, FoxO3 deficiency strongly potentiated tumor formation in nude mice and rendered cholangiocarcinoma xenografts resistant to cisplatin-induced cell death by activating Nrf2. Additionally, we found that clinical cholangiocarcinoma samples displayed FoxO3-Keap1 down-regulation and Nrf2 hyperactivation, underscoring the essential roles of these proteins in cholangiocarcinoma development. CONCLUSION: Our results unravel a unique mechanism underlying the tumor suppressor function of FoxO3 through constraining Nrf2 signaling. (Hepatology 2016;63:1914-1927). PMID- 26857211 TI - Long-term antiplatelet therapy following myocardial infarction: implications of PEGASUS-TIMI 54. AB - Dual antiplatelet therapy (DAPT) is standard treatment for patients with acute coronary syndromes (ACS), typically comprising the use of aspirin with either an irreversible thienopyridine P2Y12 inhibitor, clopidogrel or prasugrel, or reversibly binding ticagrelor. Pivotal studies led to guidelines recommending DAPT for up to 12 months post-ACS. Despite this, there remains a significant burden of coronary artery disease (CAD)-related events up to and after this period. Recent meta-analyses, including both patients with ACS and patients with stable CAD treated with DAPT following percutaneous coronary intervention, have suggested that long-term thienopyridine-based DAPT reduces the risks of myocardial infarction (MI) and stent thrombosis but may paradoxically increase all-cause mortality risk. The PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 54) study examined the effects of long-term DAPT with aspirin and ticagrelor, compared with aspirin alone, on major adverse cardiovascular events (MACE) and complications, including bleeding in patients with prior history of MI. It showed that, over a 3 year period, ticagrelor reduced the risk of MACE but increased non-fatal bleeding risk. Overall, the PEGASUS-TIMI 54 results demonstrate that patients with a history of ACS deemed to be at high risk of further ischaemic events, particularly those in whom the risks of ischaemic events and cardiovascular death outweigh the risk of life-threatening bleeding, may benefit from prolonged ticagrelor-based DAPT. Guidelines are emerging which reflect this. The relationship between aspirin and ticagrelor, particularly with regard to aspirin dosing, remains to be fully elucidated and attention has recently been turned to the option of ticagrelor monotherapy. Future studies will explore optimal individualised strategies for long-term antiplatelet therapy. PMID- 26857212 TI - Performance of 2014 NICE defibrillator implantation guidelines in heart failure risk stratification. AB - OBJECTIVE: Define the real-world performance of recently updated National Institute for Health and Care Excellence guidelines (TA314) on implantable cardioverter-defibrillator (ICD) use in people with chronic heart failure. METHODS: Multicentre prospective cohort study of 1026 patients with stable chronic heart failure, associated with left ventricular ejection fraction (LVEF) <=45% recruited in cardiology outpatient departments of four UK hospitals. We assessed the capacity of TA314 to identify patients at increased risk of sudden cardiac death (SCD) or appropriate ICD shock. RESULTS: The overall risk of SCD or appropriate ICD shock was 2.1 events per 100 patient-years (95% CI 1.7 to 2.6). Patients meeting TA314 ICD criteria (31.1%) were 2.5-fold (95% CI 1.6 to 3.9) more likely to suffer SCD or appropriate ICD shock; they were also 1.5-fold (95% CI 1.1 to 2.2) more likely to die from non-cardiovascular causes and 1.6-fold (95% CI 1.1 to 2.3) more likely to die from progressive heart failure. Patients with diabetes not meeting TA314 criteria experienced comparable absolute risk of SCD or appropriate ICD shock to patients without diabetes who met TA314 criteria. Patients with ischaemic cardiomyopathy not meeting TA314 criteria experienced comparable absolute risk of SCD or appropriate ICD shock to patients with non ischaemic cardiomyopathy who met TA314 criteria. CONCLUSIONS: TA314 can identify patients with reduced LVEF who are at increased relative risk of sudden death. Clinicians should also consider clinical context and the absolute risk of SCD when advising patients about the potential risks and benefits of ICD therapy. PMID- 26857213 TI - Global longitudinal strain is associated with heart failure outcomes in hypertrophic cardiomyopathy. AB - OBJECTIVE: We hypothesised that abnormal global longitudinal strain (GLS) would predict outcome in hypertrophic cardiomyopathy (HCM) better than current echocardiographic measures. METHODS: Retrospective analysis of risk markers in relation to outcomes in 472 patients with HCM at a single tertiary institution (2006-2012). Exclusion criteria were left ventricular (LV) hypertrophy of other origin, patients in atrial fibrillation, lost to follow-up and insufficient image quality to perform strain analysis. Standardised echocardiogram recordings were reviewed and standard variables and LV GLS were measured. The primary end-point included all cardiac deaths, appropriate defibrillator shocks and heart failure (HF) admissions. The secondary end-point was death by HF and admissions related to HF. RESULTS: Mean age was 50.0+/-15.0 years; 322 (68%) were men. At a median of 4.3 years (IQR 0.1-7.8) follow-up, 21 (4.4%) patients experienced cardiovascular death: 6 (1.3%) died from HF, 13 (2.7%) had sudden cardiac death and 2 (0.4%) died secondary to stroke. Four (0.8%) patients experienced appropriate defibrillator shock, and 13 (2.7%) were admitted for HF. On multivariate Fine-Gray proportional hazard analyses, GLS was significantly associated with the primary end-point (HR=0.90, 95% CI 0.83 to 0.98, p=0.018) independently of age, maximal provoked LV outflow-tract gradient and LV end systolic volume. Moreover, GLS was particularly associated with the secondary end point (HR=0.82, 95% CI 0.75 to 0.90, p<0.0001) independently of age, previous atrial fibrillation, New York Heart Association (NYHA) class III-IV, LV end systolic volume, E/E', and outflow-tract gradient. Survival curves confirmed that GLS was associated with HF events (GLS <15.6%, p=0.0035). CONCLUSIONS: In patients with HCM, reduced GLS is an independent factor associated with poor cardiac outcomes, and particularly HF outcomes. PMID- 26857215 TI - Visual biases in judging body weight. AB - OBJECTIVES: There has been a steady rise in obesity levels in Western countries, and a contributory factor is people's failure to recognize weight gain. Two important visual perceptual biases, contraction bias and Weber's law, that have hitherto been ignored in the obesity literature could contribute to this problem. Contraction bias predicts that the weight of obese bodies will be underestimated and the degree of underestimation will increase as body mass index (BMI) increases. Weber's law predicts that change in the body size will become progressively harder to detect as their BMI increases. METHODS: In Experiment 1, 29 women participants estimated the weight of 120 women varying in their body mass. In Experiment 2, 28 women participants judged which body was the heavier in a 2-alternative forced choice paradigm. RESULTS: In Experiment 1, as predicted the participants showed a progressive underestimation of overweight and obese bodies, beta1 = 0.71, t = 26.96, p < .0001. For Experiment 2, there was a significant effect of the BMI of the bodies being judged on the just noticeable difference needed to discriminate between them: F(1, 196) = 89.39, p < .0001 for 3D bodies and F(1, 86.5) = 44.57, p < .0001 for digital photographs. CONCLUSIONS: Normal visual perceptual biases influence our ability to determine body size: contraction bias and Weber's law mean that as bodies become overweight and obese, it is harder to judge their weight and detect any increase in size. These effects may therefore compromise people's ability to recognize weight gain and undertake compensatory weight control behaviours. Statement of contribution What is already known on this subject? It is common knowledge that obesity levels in the West are rapidly rising and that people fail to recognize weight gain. What has not been widely recognized before is that there are sound perceptual reasons for this failure. Here, we identify two such perceptual biases. What does this study add? Weber's law and contraction bias compromise people's ability to recognize weight gain. It becomes progressively harder to discriminate the size of bodies as their body mass index increases. This compromises the ability to recognize weight gain and undertake compensatory behaviours. PMID- 26857214 TI - Contrast-induced nephropathy following angiography and cardiac interventions. PMID- 26857217 TI - High prevalence of hypogonadism and associated impaired metabolic and bone mineral status in subfertile men. AB - OBJECTIVE: It is yet unknown to which degree young subfertile men present with signs of hypogonadism and whether low testosterone concentration, like in older men, is associated with risk of osteoporosis and metabolic derangements in those subjects. The objective was therefore to investigate the prevalence of hypogonadism and its association with metabolic and bone parameters in young subfertile men. DESIGN: Cross-sectional case-control study. PATIENTS: Men from infertile couples (n = 192); 18-50 years; sperm concentration <20 * 10(6) /ml and population-based age-matched controls (n = 199). MEASUREMENTS: Blood sampling, anthropometrics, blood pressure, ankle-brachial index and assessment by dual energy X-ray absorptiometry were undertaken. Odds ratios of biochemical hypogonadism (total testosterone <8.0 nmol/l and/or luteinizing hormone >=8.6 IU/l and/or ongoing androgen replacement therapy) were calculated. Serum concentrations of sex hormones, lipids, glucose, insulin and HbA1c were assessed and bone mineral density (BMD) evaluated. RESULTS: Compared to controls, the risk of hypogonadism was increased among subfertile men (OR 10; 95% CI, 5.1, 22), being highest in those with nonobstructive azoospermia. Hypogonadal men had higher HbA1c concentration (mean diff. 2.8 mmol/mol; 95% CI, 0.64, 4.9; P = 0.011) and lower lumbar spine BMD (mean diff. 0.05 g/cm(2) ; 95% CI, 0.01, 0.10; P = 0.032) compared to eugonadal subfertile men, even more pronounced in subfertile men with subnormal testosterone levels. CONCLUSION: Young subfertile men have 10 times increased OR of hypogonadism, which is linked to increased HbA1c and decreased bone mineralization. Endocrine assessment and, if needed, measures to prevent metabolic sequelae and osteoporosis should be included in the routine management of men from infertile couples. PMID- 26857218 TI - Contact sensitizers in commercial hair dye products sold in Thailand. AB - BACKGROUND: Hair dyes are known to contain potent contact allergens for which sensitization rates have increased over the last decade. OBJECTIVE: To examine the type and frequency of potent contact sensitizers labelled on hair dyes sold in metropolitan Bangkok, Thailand. METHODS: During the 2013-2014 study period, labelled ingredient information from home use and professional hair dye products was collected. RESULTS: Two hundred and fifty-two hair dye products were evaluated. One hundred and forty-nine products from 48 brands were domestically produced in Thailand, and 103 products were from 23 multinational brands produced in countries other than Thailand. Two hundred and fourteen of 252 (84.9%) hair dye products were found to contain strong skin sensitizers, with 118 (46.8%) being found in domestically produced products, and 96 (38.1%) being found in multinational brand products. Thirty-eight hair dye products (15.1%) were free of potent skin sensitizers. The number of domestically produced products (31, 20.8%) that were free of potent skin sensitizers was significantly higher (p = 0.002) than the number of multinational brand products (7, 6.8%). CONCLUSIONS: p Phenylenediamine was the most prevalent potent sensitizer found among domestically produced hair dyes available on the market. Our findings indicate regional differences in hair dye allergen exposure. PMID- 26857220 TI - Threshold Evolution as an Analysis of the Different Pulse Frequencies in Rechargeable Systems for Spinal Cord Stimulation. AB - INTRODUCTION: Pulse frequency (Fc) is one of the most important parameters in neurostimulation, with Pulse Amplitude (Pw) and Amplitude (I). Up to certain Fc, increasing the number of pulses will generate action potentials in neighboring neural structures and may facilitate deeper penetration of the electromagnetic fields. In addition, changes in frequency modify the patient's sensation with stimulation. MATERIALS/METHODS: Fifty patients previously implanted with rechargeable current control spinal cord stimulation. With pulse width fixed at 300 MUsec, we stimulated at 26 different Fc values between 40 and 1200 Hz and determine the influence of these changes on different stimulation thresholds: perception threshold (Tp ), therapeutic perception (Tt), and discomfort threshold (Td). Simultaneously, paresthesia coverage of the painful area and patient's sensation and satisfaction related to the quality of stimulation were recorded. RESULTS: Pulse Fc is inversely proportional to stimulation thresholds and this influence is statistically significant (p < 0.05). As Pulse Fc increased from 40 to 1200 Hz, the mean threshold decreases from 7.25 to 1.38 mA (Tp ), 8.17 to 1.63 (Tt ), and 9.20 to 1.85 (Td). Significant differences for Tp and Tt began at 750 Hz (Tp , Tt ) and at 650 Hz for Td. No significant influence was found regarding paresthesia coverage. As expected, Fc affects significantly patient's sensation and satisfaction. DISCUSSION: Changes in Fc affect the quality of paresthesias. Within the evaluated parameters higher frequencies are inversely proportional to stimulation thresholds and Tt. It seems that Fc is a vital parameter to achieve therapeutic success. CONCLUSIONS: Changes in Fc is a useful parameter to modulate the patient's sensory perception. Fc can be successfully used to adjust the quality of the paresthesias and to modify patient's subjective sensation. We showed that as the frequency increases, the patient's satisfaction with the perceived sensation decreases, suggesting that higher Fc may need to be set up at subthreshold amplitude to achieve positive response. PMID- 26857219 TI - Simultaneous mapping of water shift and B1 (WASABI)-Application to field Inhomogeneity correction of CEST MRI data. AB - PURPOSE: Together with the development of MRI contrasts that are inherently small in their magnitude, increased magnetic field accuracy is also required. Hence, mapping of the static magnetic field (B0 ) and the excitation field (B1 ) is not only important to feedback shim algorithms, but also for postprocess contrast correction procedures. METHODS: A novel field-inhomogeneity mapping method is presented that allows simultaneous mapping of the water shift and B1 (WASABI) using an off-resonant rectangular preparation pulse. The induced Rabi oscillations lead to a sinc-like spectrum in the frequency-offset dimension and allow for determination of B0 by its symmetry axis and of B1 by its oscillation frequency. RESULTS: Stability of the WASABI method with regard to the influences of T1 , T2 , magnetization transfer, and repetition time was investigated and its convergence interval was verified. B0 and B1 maps obtained simultaneously by means of WASABI in the human brain at 3 T and 7 T can compete well with maps obtained by standard methods. Finally, the method was applied successfully for B0 and B1 correction of chemical exchange saturation transfer MRI (CEST-MRI) data of the human brain. CONCLUSION: The proposed WASABI method yields a novel simultaneous B0 and B1 mapping within 1 min that is robust and easy to implement. Magn Reson Med 77:571-580, 2017. (c) 2016 International Society for Magnetic Resonance in Medicine. PMID- 26857221 TI - A Technique to Make Multiple Proximal Anastomoses with One HEARTSTRING Suture Device. AB - The HEARTSTRING device allows a secure proximal anastomosis, but one device is typically used for each anastomosis. We report a technique to make multiple proximal anastomoses with one HEARTSTRING suture device. doi: 10.1111/jocs.12706 (J Card Surg 2016;31:206-207). PMID- 26857216 TI - Microenvironmental regulation of oligodendrocyte replacement and remyelination in spinal cord injury. AB - Myelin is a proteolipid sheath enwrapping axons in the nervous system that facilitates signal transduction along the axons. In the central nervous system (CNS), oligodendrocytes are specialized glial cells responsible for myelin formation and maintenance. Following spinal cord injury (SCI), oligodendroglia cell death and myelin damage (demyelination) cause chronic axonal damage and irreparable loss of sensory and motor functions. Accumulating evidence shows that replacement of damaged oligodendrocytes and renewal of myelin (remyelination) are promising approaches to prevent axonal degeneration and restore function following SCI. Neural precursor cells (NPCs) and oligodendrocyte progenitor cells (OPCs) are two main resident cell populations in the spinal cord with innate capacities to foster endogenous oligodendrocyte replacement and remyelination. However, due to the hostile microenvironment of SCI, the regenerative capacity of these endogenous precursor cells is conspicuously restricted. Activated resident glia, along with infiltrating immune cells, are among the key modulators of secondary injury mechanisms that create a milieu impermissible to oligodendrocyte differentiation and remyelination. Recent studies have uncovered inhibitory roles for astrocyte-associated molecules such as matrix chondroitin sulfate proteoglycans (CSPGs), and a plethora of pro-inflammatory cytokines and neurotoxic factors produced by activated microglia/macrophages. The quality of axonal remyelination is additionally challenged by dysregulation of the supportive growth factors required for maturation of new oligodendrocytes and axo oligodendrocyte signalling. Careful understanding of factors that modulate the activity of endogenous precursor cells in the injury microenvironment is a key step in developing efficient repair strategies for remyelination and functional recovery following SCI. PMID- 26857222 TI - Cooling-induced SUMOylation of EXOSC10 down-regulates ribosome biogenesis. AB - The RNA exosome is essential for 3' processing of functional RNA species and degradation of aberrant RNAs in eukaryotic cells. Recent reports have defined the substrates of the exosome catalytic domains and solved the multimeric structure of the exosome complex. However, regulation of exosome activity remains poorly characterized, especially in response to physiological stress. Following the observation that cooling of mammalian cells results in a reduction in 40S:60S ribosomal subunit ratio, we uncover regulation of the nuclear exosome as a result of reduced temperature. Using human cells and an in vivo model system allowing whole-body cooling, we observe reduced EXOSC10 (hRrp6, Pm/Scl-100) expression in the cold. In parallel, both models of cooling increase global SUMOylation, leading to the identification of specific conjugation of SUMO1 to EXOSC10, a process that is increased by cooling. Furthermore, we define the major SUMOylation sites in EXOSC10 by mutagenesis and show that overexpression of SUMO1 alone is sufficient to suppress EXOSC10 abundance. Reducing EXOSC10 expression by RNAi in human cells correlates with the 3' preribosomal RNA processing defects seen in the cold as well as reducing the 40S:60S ratio, a previously uncharacterized consequence of EXOSC10 suppression. Together, this work illustrates that EXOSC10 can be modified by SUMOylation and identifies a physiological stress where this regulation is prevalent both in vitro and in vivo. PMID- 26857224 TI - Determination of the energy value of corn distillers dried grains with solubles containing different oil levels when fed to growing pigs. AB - This experiment used indirect calorimetry to determine the net energy (NE) content of five corn distillers dried grains with solubles (corn DDGS) containing different oil levels and to compare the NE obtained using indirect calorimetry with that calculated using previously published prediction equations. There were two samples of high-oil DDGS, one sample of medium-oil DDGS and two samples of low-oil DDGS. Twelve barrows (initial BW of 32.8 +/- 2.0 kg) were used in a repeated 3 * 6 Youden square design with three periods and six diets. The diets were comprised of a corn-soybean meal basal diet and five diets containing 29.25% of one of the corn DDGS added at the expense of corn and soybean meal. During each period, the pigs were individually housed in metabolism crates for 16 days which included 7 days for adaption to feed and environmental conditions. On day 8, the pigs were transferred to respiration chambers and fed one of the six diets at 2300 kJ ME/kg BW0.6 /day. Faeces and urine were collected from day 9 to 13 and heat production (HP) was also measured. From day 14 to 15, the pigs were fed 893 kJ ME/kg BW0.6 /day to allow them to adapt from the fed to the fasted state. On the last day of each period (day 16), the pigs were fasted and fasting HP was measured. The digestible energy value was 16.0, 17.1 and 15.3 MJ/kg DM, the metabolizable energy value was 14.6, 15.5 and 13.7 MJ/kg DM and the NE value was 10.7, 11.0 and 9.4 MJ/kg DM, for the high-oil, medium-oil and low-oil corn DDGS, respectively. The NE obtained with indirect calorimetry in the present study did not differ from values calculated using previously published prediction equations. PMID- 26857225 TI - Technological developments for small-scale downstream processing of cell therapies. AB - Despite considerable regulatory and clinical hurdles, the development and use of cell-based therapies are gaining momentum. As more of these therapies move toward commercial approval and larger-scale distribution, associated manufacturing and processing technologies are being advanced. Modern technologies directed at downstream processing seek to distribute such therapies from the manufacturing site to the patient more efficiently and reliably. Novel small-scale downstream solutions boost the transformation of cell therapies from abstraction to reality. PMID- 26857226 TI - Dopaminergic-primed fetal liver mesenchymal stromal-like cells can reverse parkinsonian symptoms in 6-hydroxydopamine-lesioned mice. AB - BACKGROUND AIMS: Cell replacement therapy is considered a promising alternative in the treatment of degenerative diseases, and in this context, mesenchymal stromal cells (MSCs) have been proposed for transplantation in Parkinson disease (PD). Thus far, the results of animal studies are found to be inconsistent and inconclusive regarding the therapeutic ability of the cells. This study investigated the efficacy of fetal liver (FL)-MSC-derived dopaminergic (DA) neuronal primed cells for correction of parkinsonian symptoms in mice. METHODS: FL-MSCs were differentiated for 21 days in the presence of a combination of neurotropic factors. The extent of cellular reprogramming was analyzed by quantitative polymerase chain reaction for DA-specific neuronal gene expressions and protein expressions by immuno-cytochemistry. The functionality of the cells was determined by electrophysiology and dopamine release assays. Ten-day-primed neuron-like cells or unprimed MSCs were transplanted into the 6-hydroxydopamine (6-OHDA)-lesioned striatum using a stereotaxic device. Dopamine-secreting properties and behavioral studies were used to assess improvement of parkinsonian symptoms. RESULTS: The differentiated cells expressed DA-specific genes and proteins, while exhibiting a high level of voltage-gated potassium current. Furthermore, neuronal primed cells differentiated into tyrosine hydroxylase immunoreactive and dopamine-secreting functional neuron-like cells. Symptomatic correction of PD in the recipient mice within 2 months of transplantation was also observed. DISCUSSION: FL-MSC-derived primed neuron-like cells integrated into the striatum of PD mice, improving parkinsonian symptoms. This study demonstrates an effective cell-based therapy for PD. PMID- 26857223 TI - Lack of tRNA-i6A modification causes mitochondrial-like metabolic deficiency in S. pombe by limiting activity of cytosolic tRNATyr, not mito-tRNA. AB - tRNA-isopentenyl transferases (IPTases) are highly conserved enzymes that form isopentenyl-N(6)-A37 (i6A37) on subsets of tRNAs, enhancing their translation activity. Nuclear-encoded IPTases modify select cytosolic (cy-) and mitochondrial (mt-) tRNAs. Mutation in human IPTase, TRIT1, causes disease phenotypes characteristic of mitochondrial translation deficiency due to mt-tRNA dysfunction. Deletion of the Schizosaccharomyces pombe IPTase (tit1-Delta) causes slow growth in glycerol, as well as in rapamycin, an inhibitor of TOR kinase that maintains metabolic homeostasis. Schizosaccharomyces pombe IPTase modifies three different cy-tRNAs(Ser) as well as cy-tRNA(Tyr), cy-tRNA(Trp), and mt-tRNA(Trp). We show that lower ATP levels in tit1-Delta relative to tit1(+) cells are also more decreased by an inhibitor of oxidative phosphorylation, indicative of mitochondrial dysfunction. Here we asked if the tit1-Delta phenotypes are due to hypomodification of cy-tRNA or mt-tRNA. A cytosol-specific IPTase that modifies cy-tRNA, but not mt-tRNA, fully rescues the tit1-Delta phenotypes. Moreover, overexpression of cy-tRNAs also rescues the phenotypes, and cy-tRNA(Tyr) alone substantially does so. Bioinformatics indicate that cy-tRNA(Tyr) is most limiting for codon demand in tit1-Delta cells and that the cytosolic mRNAs most loaded with Tyr codons encode carbon metabolilizing enzymes, many of which are known to localize to mitochondria. Thus, S. pombe i6A37 hypomodification-associated metabolic deficiency results from hypoactivity of cy-tRNA, mostly tRNA(Tyr), and unlike human TRIT1-deficiency does not impair mitochondrial translation due to mt tRNA hypomodification. We discuss species-specific aspects of i6A37. Specifically relevant to mitochondria, we show that its hypermodified version, ms2i6A37 (2 methylthiolated), which occurs on certain mammalian mt-tRNAs (but not cy-tRNAs), is not found in yeast. PMID- 26857227 TI - Mesenchymal stromal cells from the foreskin: Tissue isolation, cell characterization and immunobiological properties. AB - BACKGROUND AIMS: Because of their self-renewal capacity, multilineage potential and immunomodulatory properties, MSCs are an attractive tool for cell-based immunotherapy strategies. Foreskin, considered as a biological waste material, has been shown to be a reservoir of therapeutic cells. METHODS: MSCs were isolated from different foreskin samples, maintained under in vitro culture and defined according to the International Society for Cellular Therapy (ISCT) criteria. We subsequently determined their main cell characteristics as well as their immunobiological properties. The following parameters were determined: (i) morphology and phenotype, (ii) proliferative and clonogenic potentials, (iii) tri lineage differentiation ability, (iv) immunological profile, (v) immunomodulatory properties and (vi) protein and messenger RNA expression/secretion profile of immunoregulatory cytokines/factors as well as the pattern of toll-like receptors (TLRs). By using a pro-inflammatory cytokine cocktail, we also evaluated the influence of an inflammatory environment on their biology. RESULTS: With a typical fibroblast-like morphology and an ISCT-compliant phenotype, foreskin-MSCs (FSK-MSCs) were highly proliferative and had a great clonogenic potential. They displayed multilineage capacities and interesting immunomodulatory properties. Of importance, FSK-MSCs were not immunogenetic and were further able to inhibit T cell proliferation. We showed that several immunoregulatory cytokines and factors might be potentially involved in FSK-MSC immunomodulation with particular attention to hepatocyte growth factor and interleukin-11. Moreover, FSK-MSCs expressed several TLRs and were sensitive to the inflammatory environment by properly adjusting their profile and fate. CONCLUSIONS: Foreskin represents a new alternative source for MSCs that is compliant with ISCT criteria. Their unique immunobiological properties allow consideration of FSK-MSCs as a valuable tolerogenic product for cell-based immunotherapy. PMID- 26857228 TI - Choice of xenogenic-free expansion media significantly influences the myogenic differentiation potential of human bone marrow-derived mesenchymal stromal cells. AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have great potential for use in cell-based therapies for restoration of structure and function of many tissue types including smooth muscle. METHODS: We compared proliferation, immunophenotype, differentiation capability and gene expression of bone marrow derived MSCs expanded in different media containing human serum, plasma and platelet lysate in combination with commonly used protocols for myogenic, osteogenic, chondrogenic and adipogenic differentiation. Moreover, we developed a xenogenic-free protocol for myogenic differentiation of MSCs. RESULTS: Expansion of MSCs in media complemented with serum, serum + platelet lysate or plasma + platelet lysate were multipotent because they differentiated toward four mesenchymal (myogenic, osteogenic, chondrogenic, adipogenic) lineages. Addition of platelet lysate to expansion media increased the proliferation of MSCs and their expression of CD146. Incubation of MSCs in medium containing human serum or plasma plus 5% human platelet lysate in combination with smooth muscle cell (SMC) inducing growth factors TGFbeta1, PDGF and ascorbic acid induced high expression of ACTA2, TAGLN, CNN1 and/or MYH11 contractile SMC markers. Osteogenic, adipogenic and chondrogenic differentiations served as controls. DISCUSSION: Our study provides novel data on the myogenic differentiation potential of human MSCs toward the SMC lineage using different xenogenic-free cell culture expansion media in combination with distinct differentiation medium compositions. We show that the choice of expansion medium significantly influences the differentiation potential of human MSCs toward the smooth muscle cell, as well as osteogenic, adipogenic and chondrogenic lineages. These results can aid in designing studies using MSCs for tissue-specific therapeutic applications. PMID- 26857230 TI - Hepatocyte growth factor enhances the inflammation-alleviating effect of umbilical cord-derived mesenchymal stromal cells in a bronchiolitis obliterans model. AB - BACKGROUND AIMS: Specific and effective therapy for prevention or reversal of bronchiolitis obliterans (BO) is lacking. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF) gene modified mesenchymal stromal cells (MSCs) on BO. METHODS: A mouse model of experimental BO was established by subcutaneously transplanting the tracheas from C57BL/6 mice into Balb/C recipients, which were then administered saline, Ad-HGF-modified human umbilical cord-MSCs (MSCs-HGF) or Ad-Null-modified MSCs (MSCs-Null). The therapeutic effects of MSCs-Null and MSCs-HGF were evaluated by using fluorescence-activated cell sorting (FACS) for lymphocyte immunophenotype of spleen, enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (rt-PCR) for cytokine expression, and histopathological analysis for the transplanted trachea. RESULTS: The histopathologic recovery of allograft tracheas was improved significantly after MSCs-Null and MSCs-HGF treatment and the beneficial effects were particularly observed in MSCs-HGF-treated mice. Furthermore, the allo-transplantation-induced immunophenotype disorders of the spleen, including regulatory T (Treg), T helper (Th)1, Th2 and Th17, were attenuated in both cell-treated groups. MSCs-HGF treatment reduced expression and secretion of inflammation cytokines interferon-gamma (IFN-gamma), and increased expression of anti-inflammatory cytokine interleukin (IL)-4 and IL-10. It also decreased the expression level of the profibrosis factor transforming growth factor (TGF)-beta. CONCLUSION: Treatment of BO with HGF gene modified MSCs results in reduction of local inflammation and promotion in recovery of allograft trachea histopathology. These findings might provide an effective therapeutic strategy for BO. PMID- 26857229 TI - Galectin-1 is a local but not systemic immunomodulatory factor in mesenchymal stromal cells. AB - BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have powerful immunosuppressive activity. This function of MSCs is attributed to plethora of the expressed immunosuppressive factors, such as galectin-1 (Gal-1), a pleiotropic lectin with robust anti-inflammatory effect. Nevertheless, whether Gal-1 renders or contributes to the immunosuppressive effect of MSCs has not been clearly established. Therefore, this question was the focus of a complex study. METHODS: MSCs were isolated from bone marrows of wild-type and Gal-1 knockout mice and their in vitro anti-proliferative and apoptosis-inducing effects on activated T cells were examined. The in vivo immunosuppressive activity was tested in murine models of type I diabetes and delayed-type hypersensitivity. RESULTS: Both Gal-1 expressing and -deficient MSCs inhibited T-cell proliferation. Inhibition of T cell proliferation by MSCs was mediated by nitric oxide but not PD-L1 or Gal-1. In contrast, MSC-derived Gal-1 triggered apoptosis in activated T cells that were directly coupled to MSCs, representing a low proportion of the T-cell population. Furthermore, absence of Gal-1 in MSCs did not affect their in vivo immunosuppressive effect. CONCLUSIONS: These results serve as evidence that Gal-1 does not play a role in the systemic immunosuppressive effect of MSCs. However, a local contribution of Gal-1 to modulation of T-cell response by direct cell-to cell interaction cannot be excluded. Notably, this study serves a good model to understand how the specificity of a pleiotropic protein depends on the type and localization of the producing effector cell and its target. PMID- 26857231 TI - Safety evaluation of exosomes derived from human umbilical cord mesenchymal stromal cell. AB - BACKGROUND AIMS: Mounting evidence shows that non-cell-based transplantation of exosomes derived from mesenchymal stromal cells (MSCs) has more potential protective and reparative effects than MSCs have. However, whether it is safe to transplant MSC exosomes into tissues is still not clear. In this study, we evaluated the safety of transplantation of exosomes derived from human umbilical cord MSCs (hucMSC exosomes). METHODS: hucMSC exosomes were incubated with the cardiac blood from a healthy rabbit, and hemolysis was observed. For analysis of vascular and muscle stimulation, pyrogen, systemic anaphylaxis and hematology indexes, hucMSC exosomes were given to rabbits, guinea pigs and rats. The histological changes in the vascular and muscle sites of injection in rabbits were analyzed by hematoxylin and eosin staining. Allergy symptoms in guinea pigs and rectal temperature of rabbits were observed and recorded. To study safety in vivo, hucMSC exosomes were infused intravenously into rats with acute myocardial infarction. Rats' weight was measured and tail vein blood was collected to evaluate liver and renal function. RESULTS: hucMSC exosomes had a protective effect on weight loss and had no adverse effects on liver or renal function. Other detections, such as hemolysis, vascular and muscle stimulation, systemic anaphylaxis, pyrogen and hematology indexes, also showed that hucMSC exosomes were applicable. CONCLUSIONS: hucMSC exosomes are well tolerated in animal models. This study provides evidence for the safety of intravenous infusion in future clinical therapy. PMID- 26857232 TI - The effects of culture conditions on the functionality of efficiently obtained mesenchymal stromal cells from human cord blood. AB - BACKGROUND AIMS: Cord blood (CB) is an attractive source of mesenchymal stromal cells (MSCs) because of its abundant availability and ease of collection. However, the success rate of generating CB-MSCs is low. In this study, our aim was to demonstrate the efficiency of our previously described method to obtain MSCs from CB and further characterize them and to study the effects of different culture conditions on MSCs. METHODS: CB-MSC cultures were established in low oxygen (3%) conditions on fibronectin in 10% fetal bovine serum containing culture medium supplemented with combinations of growth factors. Cells were characterized for their adipogenic, osteogenic and chondrogenic differentiation capacity; phenotype; and HOX gene expression profile. The functionality of the cells cultured in different media was tested in vitro with angiogenesis and T cell proliferation assays. RESULTS: We demonstrate 87% efficacy in generating MSCs from CB. The established cells had typical MSC characteristics with reduced adipogenic differentiation potential and a unique HOX gene fingerprint. Growth factor-rich medium and a 3% oxygen condition enhanced cell proliferation; however, the growth factor-rich medium had a negative effect on the expression of CD90. Dexamethasone-containing medium improved the capacity of the cells to suppress T-cell proliferation, whereas the cells grown without dexamethasone were more able to support angiogenesis. CONCLUSIONS: Our results demonstrate that the composition of expansion medium is critical for the functionality of MSCs and should always be appropriately defined for each purpose. PMID- 26857233 TI - A humanized system to expand in vitro amniotic fluid-derived stem cells intended for clinical application. AB - BACKGROUND AIMS: The amniotic fluid is a new source of multipotent stem cells with therapeutic potential for human diseases. In agreement with the regulatory requirement to reduce and possibly to avoid animal-derived reagents in the culture of cells intended for cell therapy, bovine serum, the most common supplement in the culture medium, was replaced by human platelet-derived growth factors. METHODS: We tested a new culture medium to expand monolayers of human amniotic fluid stem cells (hAFSC) for clinical use. The AFSC were isolated by c Kit selection and expanded in media supplemented with either bovine serum or a human platelet lysate (Lyset). RESULTS: We compared proliferation kinetics, colony-forming unit percentage, multilineage differentiation, immunophenotypic characterization and inhibition of peripheral blood mononuclear cell proliferation of the two AFSC cell cultures and we found no significant differences. Moreover, the karyotype analysis of the cells expanded in the presence of the platelet lysate did not present cytogenetic abnormalities and in vitro and in vivo studies revealed no cell tumorigenicity. CONCLUSIONS: Platelet derivatives represent a rich source of growth factors that can play a safety role in the homeostasis, proliferation and remodeling of tissue healing. We propose human platelet extracts as a preferential alternative to animal serum for the expansion of stem cells for clinical applications. PMID- 26857234 TI - Endothelial progenitor cells promote efficient ex vivo expansion of cord blood derived hematopoietic stem/progenitor cells. AB - BACKGROUND AIMS: Cord blood (CB) hematopoietic stem cell transplantation has often been limited by the scarcity of stem cells. Therefore, the number of CB hematopoietic stem/progenitor cells (HSPCs) should be increased while maintaining the stem cell characteristics. METHODS: We designed an ex vivo culture system using endothelial progenitor cells (EPCs) as stroma to determine the capacity of expanding CB-HSPCs in a defined medium, the effect on engraftment of the expanded cells in a mouse model and the underlying mechanism. RESULTS: After 7 days of culture, compared with those cultured with cytokines alone (3.25 +/- 0.59), CD34+ cells under contact and non-contact co-culture with EPCs were expanded by 5.38 +/ 0.61 (P = 0.003) and 4.06 +/- 0.43 (P = 0.025)-fold, respectively. Direct cell to-cell contact co-culture with EPCs resulted in more primitive CD34+ CD38- cells than stroma-free culture (156.17 +/- 21.32 versus 79.12 +/- 19.77-fold; P = 0.010). Comparable engraftment of day 7 co-cultured HSPCs with respect to HSPCs at day 0 in nonobese diabetic-severe combined immunodeficiency disease (NOD/SCID) mice was measured as a percentage of chimerism (13.3% +/- 11.0% versus 16.0% +/- 14.3%; P = 0.750). EPCs highly expressed interleukin 6 (IL6) and angiopoietin 1 (ANGPT1), the hematopoietic- related cytokines. A higher transcriptional level of WNT5A genes in EPCs and co-cultured HSPCs suggests that the activation of Wnt signaling pathway may play a role in HSPCs' expansion ex vivo. DISCUSSION: These data demonstrated that EPCs improve the CD34+ population but do not compromise the repopulating efficacy of the amplified HSPCs, possibly via cytokine secretion and Wnt signaling pathway activation. PMID- 26857236 TI - Eliminating the use of intravenous glass bottles using a FOCUS-PDCA model and providing a practical stability reference guide. AB - OBJECTIVES: To identify the intravenous (IV) medications that are prepared in glass bottles at the institution and establish which of these medications can be prepared in flexible IV bags such as polyvinyl chloride (PVC) or non-PVC instead of glass bottles. The cost implication of switching from glass bottles to flexible IV bags was calculated. METHODS: A study using FOCUS-PDCA model to identify IV medications prepared in glass bottles and establish which of these medications could be prepared in IV bags (PVC or non-PVC). The cost impact of switching from glass bottles to IV plastic bags (including PVC or non-PVC) was calculated. The stability data obtained were used as a reference for updating pharmacy internal IV preparation charts. KEY FINDINGS: A total of 17 IV medications were found to be prepared in IV glass bottles. Of these 17 medications, only 8 (47%) were prepared in IV glass bottles due to incompatibility with PVC bags. For 7 (41%) of the medications, of which 6 were monoclonal antibodies (MABs), the reason for preparation in glass bottles was unclear as these medications are compatible with either PVC or non-PVC or both. The potential cost savings associated with switching all of the identified medications to IV plastic bags (either non-PVC or PVC) exceeded $200 000. CONCLUSIONS: The elimination of glass bottles within the institution resulted in a significant cost saving. The use of FOCUS-PDCA model can help healthcare institution achieve significant improvements in process and realize significant cost savings. PMID- 26857235 TI - Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells. AB - BACKGROUND: Relapsing disease is a major challenge after hematopoietic cell transplantation for hematological malignancies. Myxoma virus (MYXV) is an oncolytic virus that can target and eliminate contaminating cancer cells from auto-transplant grafts. The aims of this study were to examine the impact of MYXV on normal hematopoietic stem and progenitor cells and define the optimal treatment conditions for ex vivo virotherapy. METHODS: Bone marrow (BM) and mobilized peripheral blood stem cells (mPBSCs) from patients with hematologic malignancies were treated with MYXV at various time, temperature and incubation media conditions. Treated BM cells from healthy normal donors were evaluated using flow cytometry for MYXV infection, long-term culture-initiating cell (LTC IC) assay and colony-forming cell (CFC) assay. RESULTS: MYXV initiated infection in up to 45% of antigen-presenting monocytes, B cells and natural killer cells; however, these infections were uniformly aborted in >95% of all cells. Fresh graft sources showed higher levels of MYXV infection initiation than cryopreserved specimens, but in all cases less than 10% of CD34(+) cells could be infected after ex vivo MYXV treatment. MYXV did not impair LTC-IC colony numbers compared with mock treatment. CFC colony types and numbers were also not impaired by MYXV treatment. MYXV incubation time, temperature or culture media did not significantly change the percentage of infected cells, LTC-IC colony formation or CFC colony formation. CONCLUSIONS: Human hematopoietic cells are non-permissive for MYXV. Human hematopoietic stem and progenitor cells were not infected and thus unaffected by MYXV ex vivo treatment. PMID- 26857237 TI - Long-term antihypertensive effects of far-infrared ray irradiated from wooden board in spontaneously hypertensive rats. AB - BACKGROUND: Far-infrared ray (FIR) has been widely used in promoting health and has been shown to exert beneficial effects in vascular function. The non-thermal effect of FIR has been found to play a significant role in the protective effect on some vascular-related diseases, but its protective effects and use against hypertension have not been clearly presented. METHODS: In the present study, by using a wooden board coated with FIR-irradiated materials, we evaluated the long term antihypertensive effect on spontaneously hypertensive rats (SHRs) in the environment in contact with the FIR-irradiated wooden board. SHRs were placed on the wooden board with or without FIR radiation for 4 weeks. RESULTS: The systolic blood pressure (BP) of SHRs undergoing different treatments was measured weekly using a tail-cuff method. FIR radiation significantly reduced the systolic BP of the SHRs along with a decreasing plasma level of angiotensin II and an increasing plasma level of bradykinin. In addition, long-term contact of FIR did not significantly affect the BP in normotensive Wistar Kyoto rats (WKYs). CONCLUSIONS: Our results provided the evidence based on which FIR radiation could be considered an effective non-pharmacological choice for preventing hypertension. PMID- 26857238 TI - Diagnosis of TIA (DOT) score--design and validation of a new clinical diagnostic tool for transient ischaemic attack. AB - BACKGROUND: The diagnosis of Transient Ischaemic Attack (TIA) can be difficult and 50-60% of patients seen in TIA clinics turn out to be mimics. Many of these mimics have high ABCD2 scores and fill urgent TIA clinic slots inappropriately. A TIA diagnostic tool may help non-specialists make the diagnosis with greater accuracy and improve TIA clinic triage. The only available diagnostic score (Dawson et al) is limited in scope and not widely used. The Diagnosis of TIA (DOT) Score is a new and internally validated web and mobile app based diagnostic tool which encompasses both brain and retinal TIA. METHODS: The score was derived retrospectively from a single centre TIA clinic database using stepwise logistic regression by backwards elimination to find the best model. An optimum cutpoint was obtained for the score. The derivation and validation cohorts were separate samples drawn from the years 2010/12 and 2013 respectively. Receiver Operating Characteristic (ROC) curves and area under the curve (AUC) were calculated and the diagnostic accuracy of DOT was compared to the Dawson score. A web and smartphone calculator were designed subsequently. RESULTS: The derivation cohort had 879 patients and the validation cohort 525. The final model had seventeen predictors and had an AUC of 0.91 (95% CI: 0.89-0.93). When tested on the validation cohort, the AUC for DOTS was 0.89 (0.86-0.92) while that of the Dawson score was 0.77 (0.73-0.81). The sensitivity and specificity of the DOT score were 89% (CI: 84%-93%) and 76% (70%-81%) respectively while those of the Dawson score were 83% (78%-88%) and 51% (45%-57%). Other diagnostic accuracy measures (DOT vs. Dawson) include positive predictive values (75% vs. 58%), negative predictive values (89% vs. 79%), positive likelihood ratios (3.67 vs. 1.70) and negative likelihood ratios (0.15 vs. 0.32). CONCLUSION: The DOT score shows promise as a diagnostic tool for TIA and requires independent external validation before it can be widely used. It could potentially improve the triage of patients assessed for suspected TIA. PMID- 26857239 TI - Peripheral neuropathy reduces asymmetries in inter-limb transfer in a visuo-motor task. AB - Asymmetry of inter-limb transfer has been associated with the specialization of the dominant and non-dominant motor system. Reductions of asymmetry have been interpreted as behavioural evidence showing a decline of hemispheric lateralization. A previous study showed that ageing did not qualitatively change the inter-limb transfer asymmetry of a visuo-motor task. The current study elaborates on these findings; it examines whether diminished somatosensory information as a result of peripheral neuropathy (PN) adversely affects inter limb transfer asymmetry. Twenty individuals affected by PN and 20 older controls were recruited and divided equally across two groups. One group trained a visuo motor task with the right hand while the other group trained it with the left hand. Performance (initial direction error) of the untrained hand before and after training was collected to determine learning effects from inter-limb transfer. Similar to previous studies, the current study showed asymmetric inter limb transfer in older controls. In contrast, PN showed inter-limb transfer in both directions indicating that PN reduces inter-limb transfer asymmetry. Increased bilateral hemispheric recruitment is suggested to be responsible for this reduced asymmetry which may compensate for deteriorated tactile and/or proprioceptive inputs in PN. Two possible hypotheses are discussed explaining the relationship between declined somatosensory information and increases in bilateral hemispheric recruitment. PMID- 26857240 TI - Unclassifiable arrhythmic cardiomyopathy associated with Emery-Dreifuss caused by a mutation in FHL1. AB - Emery-Dreifuss muscular dystrophy (EDMD) is a heterogeneous genetic disorder characterized by peripheral muscular weakness often associated with dilated cardiomyopathy. We characterize clinically a large family with a mutation in FHL1 gene (p.Cys255Ser). Penetrance was 44%, 100% for males and 18% for females. The heart was the main organ involved. Affected adult males had mild hypertrophy, systolic dysfunction and restriction with non-dilated ventricles. Carriers had significant QTc prolongation. The proband presented with resuscitated cardiac arrest. There were two transplants. Pathological study of explanted heart showed fibrofatty replacement and scarring consistent with arrhythmogenic cardiomyopathy and prominent left ventricular trabeculations. Myopathic involvement was evident in all males. Females had no significant neuromuscular disease. Mutations in FHL1 cause unclassifiable cardiomyopathy with coexisting EDMD. Prognosis is poor and systolic impairment and arrhythmias are frequent. Thrombopenia and raised creatine phosphokinase should raise suspicion of an FHL-1 disorder in X-linked cardiomyopathy. PMID- 26857242 TI - Intercellular adhesion molecule 1 serves as a primary cognate receptor for the Type IV pilus of nontypeable Haemophilus influenzae. AB - Nontypeable Haemophilus influenzae (NTHI) utilizes the Type IV pilus (Tfp) to adhere to respiratory tract epithelial cells thus colonizing its human host; however, the host cell receptor to which this adhesive protein binds is unknown. From a panel of receptors engaged by Tfp expressed by other bacterial species, we showed that the majority subunit of NTHI Tfp, PilA, bound to intercellular adhesion molecule 1 (ICAM1) and that this interaction was both specific and of high affinity. Further, Tfp-expressing NTHI inoculated on to polarized respiratory tract epithelial cells that expressed ICAM1 were significantly more adherent compared to Tfp-deficient NTHI or NTHI inoculated on to epithelial cells to which ICAM1 gene expression was silenced. Moreover, pre-incubation of epithelial cells with recombinant soluble PilA (rsPilA) blocked adherence of NTHI, an outcome that was abrogated by admixing rsPilA with ICAM1 prior to application on to the target cells. Epithelial cells infected with adenovirus or respiratory syncytial virus showed increased expression of ICAM1; this outcome supported augmented adherence of Tfp-expressing NTHI. Collectively, these data revealed the cognate receptor for NTHI Tfp as ICAM1 and promote continued development of a Tfp-targeted vaccine for NTHI-induced diseases of the airway wherein upper respiratory tract viruses play a key predisposing role. PMID- 26857241 TI - A Review of the Clinical Side Effects of Bone Morphogenetic Protein-2. AB - Bone morphogenetic protein-2 (BMP-2) is currently the only Food and Drug Administration (FDA)-approved osteoinductive growth factor used as a bone graft substitute. However, with increasing clinical use of BMP-2, a growing and well documented side effect profile has emerged. This includes postoperative inflammation and associated adverse effects, ectopic bone formation, osteoclast mediated bone resorption, and inappropriate adipogenesis. Several large-scale studies have confirmed the relative frequency of adverse events associated with the clinical use of BMP-2, including life-threatening cervical spine swelling. In fact, the FDA has issued a warning of the potential life-threatening complications of BMP-2. This review summarizes the known adverse effects of BMP 2, including controversial areas such as tumorigenesis. Next, select animal models that replicate BMP-2's adverse clinical effects are discussed. Finally, potential molecules to mitigate the adverse effects of BMP-2 are reviewed. In summary, BMP-2 is a potent osteoinductive cytokine that has indeed revolutionized the bone graft substitute market; however, it simultaneously has accrued a worrisome side effect profile. Better understanding of these adverse effects among both translational scientists and clinicians will help determine the most appropriate and safe use of BMP-2 in the clinical setting. PMID- 26857244 TI - A multicenter, epidemiological study of the treatment patterns, comorbidities and hypoglycemia events of patients with type 2 diabetes and moderate or severe chronic kidney disease - the 'LEARN' study. AB - Objective Management of patients with type 2 diabetes (T2DM) and stage 3 to 5 chronic kidney disease (CKD) is challenging. The aim of the 'LEARN' study was to describe treatment patterns employed in this population and to record comorbidities, glycemic control and hypoglycemia episodes in routine clinical practice in Greece. Research design and methods 'LEARN' was a non-interventional, multicenter, cross-sectional study conducted in Greece between 15 February 2013 and 4 July 2013. A total of 120 adult patients were enrolled from four hospital sites in different geographic regions of Greece. Results Participants had a mean age of 69.1 +/- 10.3 years and a male:female ratio of 2:1. Nearly all patients (99.2%) suffered from at least one comorbidity, with hypertension (95.8%) and hyperlipidemia/dyslipidemia (78.3%) being the most prevalent. Of the overall study population, 57.5% was managed with insulin therapy only, 30.8% with oral antidiabetics only and 11.7% with a combination of insulin and oral antidiabetics. The overall rate of glycemic control, defined as glycated hemoglobin (HbA1c) <= 7.0% during the most recent assessment, was 55.0%. This rate was significantly higher among those receiving oral antidiabetics only (73.0%) compared to insulin only (47.8%) or a combination of both types of treatment (42.9%) (p = 0.03). Moreover, patients receiving oral antidiabetics only had experienced fewer hypoglycemia episodes over the last 7 days prior to the study visit (0.1 +/- 0.4) compared to patients receiving insulin only (0.9 +/ 1.7) (p = 0.03). Conclusions Although this is an observational study, it seems that oral antidiabetic therapy might be advantageous for heavily burdened T2DM patients with moderate or severe CKD in terms of glycemic control and hypoglycemia episodes. More data preferably from randomized trials is needed in order to validate this hypothesis. PMID- 26857243 TI - Clinical utility of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation. AB - BACKGROUND: Mutations in the TERT promoter, ALK rearrangement, and the BRAF V600E mutation are associated with aggressive clinicopathologic features in thyroid cancers. However, little is known about the impact of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of BRAF mutations. METHODS: We performed Sanger sequencing to detect BRAF V600E and TERT promoter mutations and both immunohistochemistry and fluorescence in situ hybridization to identify ALK rearrangement on 243 thyroid cancers. RESULTS: TERT promoter mutations were not present in 192 well-differentiated thyroid carcinomas (WDTC) without distant metastasis or in 9 medullary carcinomas. However, the mutations did occur in 40 % (12/30) of WDTC with distant metastasis, 29 % (2/7) of poorly differentiated carcinomas and 60 % (3/5) of anaplastic carcinomas. ALK rearrangement was not present in all thyroid cancers. The BRAF V600E mutation was more frequently found in WDTC without distant metastasis than in WDTC with distant metastasis (p = 0.007). In the cohort of WDTC with distant metastasis, patients with wild-type BRAF and TERT promoter had a significantly higher response rate after radioiodine therapy (p = 0.024), whereas the BRAF V600E mutation was significantly correlated with progressive disease (p = 0.025). CONCLUSIONS: The TERT promoter mutation is an independent predictor for distant metastasis of WDTC, but ALK testing is not useful for clinical decision-making in Korean patients with a high prevalence of the BRAF V600E mutation. Radioiodine therapy for distant metastasis of WDTC is most effective in patients without BRAF V600E and TERT promoter mutations. PMID- 26857245 TI - Cytosolic NADH-NAD(+) Redox Visualized in Brain Slices by Two-Photon Fluorescence Lifetime Biosensor Imaging. AB - AIM: Cytosolic NADH-NAD(+) redox state is central to cellular metabolism and a valuable indicator of glucose and lactate metabolism in living cells. Here we sought to quantitatively determine NADH-NAD(+) redox in live cells and brain tissue using a fluorescence lifetime imaging of the genetically-encoded single fluorophore biosensor Peredox. RESULTS: We show that Peredox exhibits a substantial change in its fluorescence lifetime over its sensing range of NADH NAD(+) ratio. This allows changes in cytosolic NADH redox to be visualized in living cells using a two-photon scanning microscope with fluorescence lifetime imaging capabilities (2p-FLIM), using time-correlated single photon counting. INNOVATION: Because the lifetime readout is absolutely calibrated (in nanoseconds) and is independent of sensor concentration, we demonstrate that quantitative assessment of NADH redox is possible using a single fluorophore biosensor. CONCLUSION: Imaging of the sensor in mouse hippocampal brain slices reveals that astrocytes are typically much more reduced (with higher NADH:NAD(+) ratio) than neurons under basal conditions, consistent with the hypothesis that astrocytes are more glycolytic than neurons. Antioxid. Redox Signal. 25, 553-563. PMID- 26857247 TI - Erratum to: Echocardiography for adult patients supported with extracorporeal membrane oxygenation. PMID- 26857246 TI - Increased CSF tau level is correlated with decreased lamina cribrosa thickness. AB - BACKGROUND: This study was to investigate whether the previously proposed link between Alzheimer's disease (AD) and decreased retinal nerve fiber layer thickness could be explained by the relationship between abnormal CSF profiles and optic nerve head characteristics, focusing on the influence of CSF tau protein on the lamina cribrosa (LC) thickness (LCT). METHODS: A total of 44 eyes from 18 patients with AD and 26 healthy subjects were subjected to enhanced-depth imaging volume scanning of the optic nerve using spectral-domain optical coherence tomography. The B-scan images were constructed three-dimensionally using maximum intensity projection (MIP), and the LCT was measured at three locations (superior midperipheral, midhorizontal, and inferior midperipheral) using the thin-slab MIP images. CSF levels of amyloid beta 1-42 peptide, (Abeta1 42), total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau181P) were measured from CSF samples of each subject. The relationship between the level of CSF proteins and the LCT was determined using linear regression and fractional polynomial analyses. RESULTS: Univariate regression analysis revealed that higher CSF levels of T-tau (P = 0.004) and P-tau181P (P = 0.027), as well as a smaller central corneal thickness (P = 0.032), were significantly associated with a smaller LCT. Multivariate analysis indicated that only CSF T-tau (P = 0.041) was significantly associated with the LCT. The relationship was well explained by both linear regression (R(2) = 0.179, P = 0.004) and fractional polynomial analysis (R(2) = 0.275, P = 0.001). When we performed an assessment by linear regression with an indicator, the relationship was significant both in the healthy and AD groups, with a stronger correlation found in the healthy group (regression coefficients = -1.098 vs. -0.280, P = 0.018). CONCLUSIONS: An increased CSF level of T-tau was significantly associated with a thinner LCT in both the healthy and AD groups. This result suggests that LCT could serve as a potential non-invasive indicator for increased CSF tau. The clinical meaning of the higher level of CSF T-tau in axonal degeneration of the optic nerve remains to be determined. PMID- 26857248 TI - The effectiveness of balneotherapy in chronic neck pain. AB - The aim of this study was to investigate the effectiveness of balneotherapy (BT), which is applied in addition to physical therapy (PT), in the treatment of chronic neck pain. Sixty patients with chronic neck pain were divided into study (n = 30) and control (n = 30) groups. All of the patients in both groups were treated with a 15-session standard PT program consisting of hot pack, ultrasound, and transcutaneous electrical stimulation. Patients in the study group were also treated with a 15-session BT program lasting 20 min/day in addition to the standard PT program. Visual analogue scale (VAS), modified neck disability index (mNDI), and Nottingham Health Profile (NHP) scores of all patients were evaluated at three different times as pretreatment, posttreatment, and posttreatment third week. There was no statistically significant difference between the clinical and demographic characteristics of the patients in different groups before treatment. Intragroup analysis revealed significant improvement in all parameters for both of the groups at all time intervals. Intergroup analysis uncovered the superiority of the study group. According to the results of this study, BT in combination with PT is superior to PT alone in reducing pain and disability and improving quality of life in patients with chronic neck pain. PMID- 26857249 TI - Analysis of the isomer ratios of polymethylated-DOTA complexes and the implications on protein structural studies. AB - A rigidified and symmetrical polymethylated 1,4,7,10-tetraazacyclododecane 1,4,7,10-tetraacetic acid (DOTA) ligand bearing four SSSS methyl groups in both the tetraaza ring and the acetate arms (SSSS-SSSS-M4DOTMA) was prepared. The isomer ratio of SSSS-SSSS-M4DOTMA complexed with a series of lanthanide ions was carefully investigated using RP-HPLC and NMR. A square antiprismatic (SAP) configuration was exclusively observed for the early lanthanides, while the twisted square antiprismatic (TSAP) geometry was preferred as the lanthanide ion size decreases. The late lanthanides preferentially adopted the TSAP geometry. One of the pendant arms was modified with a pyridyl disulfide group (SSSS-SSSS M8SPy) for cysteine attachment and displayed a similar isomer trend as the parent compound, Ln-SSSS-SSSS-M4DOTMA. Covalent attachment to the ubiquitin S57C mutant showed resonances whose intensities are in agreement with the isomeric population observed by RP-HPLC. Furthermore, the NOE experiments combined with quantum chemical calculations have unequivocally demonstrated that the SAP of Pr-SSSS SSSS-M4DOTMA and Pr-SSSS-SSSS-M8SPy, as well as the TSAP of Yb-SSSS-SSSS-M8SPy are more stable than their corresponding isomers. PMID- 26857253 TI - Trophic dynamics of shrinking Subarctic lakes: naturally eutrophic waters impart resilience to rising nutrient and major ion concentrations. AB - Shrinking lakes were recently observed for several Arctic and Subarctic regions due to increased evaporation and permafrost degradation. Along with lake drawdown, these processes often boost aquatic chemical concentrations, potentially impacting trophic dynamics. In particular, elevated chemical levels may impact primary productivity, which may in turn influence populations of primary and secondary consumers. We examined trophic dynamics of 18 shrinking lakes of the Yukon Flats, Alaska, that had experienced pronounced increases in nutrient (>200 % total nitrogen, >100 % total phosphorus) and ion concentrations (>100 % for four major ions combined) from 1985-1989 to 2010-2012, versus 37 stable lakes with relatively little chemical change over the same period. We found that phytoplankton stocks, as indexed by chlorophyll concentrations, remained unchanged in both shrinking and stable lakes from the 1980s to 2010s. Moving up the trophic ladder, we found significant changes in invertebrate abundance across decades, including decreased abundance of five of six groups examined. However, these decadal losses in invertebrate abundance were not limited to shrinking lakes, occurring in lakes with stable surface areas as well. At the top of the food web, we observed that probabilities of lake occupancy for ten waterbird species, including adults and chicks, remained unchanged from the period 1985-1989 to 2010-2012. Overall, our study lakes displayed a high degree of resilience to multi-trophic cascades caused by rising chemical concentrations. This resilience was likely due to their naturally high fertility, such that further nutrient inputs had little impact on waters already near peak production. PMID- 26857252 TI - Urine oxalate biological variation in patients with primary hyperoxaluria. AB - Hyperoxaluria is a well-recognised risk factor for urolithiasis and patients with primary hyperoxaluria (PH) gradually build up calcium oxalate deposits leading to chronic kidney disease. Efforts to improve treatment for PH have focused on reducing urine oxalate excretion and thus decreasing lithogenesis. To determine the efficacy of treatments designed to alter a biochemical parameter it is necessary to know the biological and analytical variation of that parameter. In this study, we estimated the intra-individual biological variation of urine oxalate excretion in patients with PH, and from this determined what would constitute a significant change in the form of a reference change value (RCV). Each patient collected four 24-h urines on consecutive weeks. The intra individual biological variation of oxalate excretion calculated from these samples ranged from 0 to 36 % with a mean of 14 %. The corresponding RCVs were 4 84 % with a mean of 32 %. This result implies that, on average, a reduction of almost one-third in urine oxalate excretion is required to prove an effect from treatment. The wide range of biological variation between individuals may reflect other, as yet unknown, determinants of oxaluria in PH, as well as inaccuracies in urine collection. The data suggest that it is more appropriate to use individual RCVs established prior to treatment to determine its efficacy: a relatively small fall in urine oxalate excretion may be outside the biological variation of some patients but not of others. PMID- 26857251 TI - Of Pesticides and Men: a California Story of Genes and Environment in Parkinson's Disease. AB - At the start of the postgenomics era, most Parkinson's disease (PD) etiology cannot be explained by our knowledge of genetic or environmental factors alone. For more than a decade, we have explored gene-environment (GxE) interactions possibly responsible for the heterogeneity of genetic as well as environmental results across populations. We developed three pesticide exposure measures (ambient due to agricultural applications, home and garden use, and occupational use) in a large population-based case-control study of incident PD in central California. Specifically, we assessed interactions with genes responsible for pesticide metabolism (PON1); transport across the blood-brain barrier (ABCB1); pesticides interfering with or depending on dopamine transporter activity (DAT/SLC6A3) and dopamine metabolism (ALDH2); impacting mitochondrial function via oxidative/nitrosative stress (NOS1) or proteasome inhibition (SKP1); and contributing to immune dysregulation (HLA-DR). These studies established some specificity for pesticides' neurodegenerative actions, contributed biologic plausibility to epidemiologic findings, and identified genetically susceptible populations. PMID- 26857254 TI - Meso-scale on-road vehicle emission inventory approach: a study on Dhaka City of Bangladesh supporting the 'cause-effect' analysis of the transport system. AB - The study aims to develop an emission inventory (EI) approach and conduct an inventory for vehicular sources in Dhaka City, Bangladesh. A meso-scale modelling approach was adopted for the inventory; the factors that influence the emissions and the magnitude of emission variation were identified and reported on, which was an innovative approach to account emissions unlike the conventional inventory approaches. Two techniques for the emission inventory were applied, viz. (i) a combined top-down and bottom-up approach that considered the total vehicle population and the average diurnal on-road vehicle speed profile in the city and (ii) a bottom-up approach that accounted for road link-specific emissions of the city considering diurnal traffic volume and speed profiles of the respective roads. For the bottom-up approach, road link-specific detailed data were obtained through field survey in 2012, where mid-block traffic count of the day, vehicle speed profile, road network and congestion data were collected principally. The emission variances for the change in transport system characteristics (like change in fuel type, AC usage pattern, increased speed and reduced congestion/stopping) were predicted and analysed in this study; congestion influenced average speed of the vehicles, and fuel types in the vehicles were identified as the major stressors. The study performance was considered reasonable when comparing with the limited number of similar studies conducted earlier. Given the increasing trend of private vehicles each year coupled with increasing traffic congestion, the city is under threat of increased vehicular emissions unless a good management strategy is implemented. Although the inventory is conducted for Dhaka and the result may be important locally, the approach adopted in this research is innovative in nature to be followed for conducting research on other urban transport systems. PMID- 26857256 TI - Key data from the 17th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV. AB - Combination antiretroviral therapy (cART) has significantly reduced HIV-related morbidity and mortality; however, residual inflammation often persists in the absence of detectable viral load. In addition, chronic use of cART and an ageing HIV-positive population present new challenges to treating physicians who must balance the need for good virological control with risk of treatment-related toxicities. Discussions at the 17th International Workshop on Co-morbidities and Adverse Drug Reactions in HIV once again sought a better understanding of the complex relationship between HIV-, treatment- and age-related factors in the development of comorbidities in those infected with HIV. Key data from the meeting pertaining to inflammatory pathways in HIV, adipose tissue metabolism, cardiovascular disease, bone health, ageing and frailty, neurocognitive dysfunction, pulmonary disease and HCV coinfection are the focus of this report. PMID- 26857255 TI - The use of rapidly synergistic cloud point extraction for the separation and preconcentration of trace amounts of Ni (II) ions from food and water samples coupling with flame atomic absorption spectrometry determination. AB - A novel improved preconcentration method known as rapidly synergistic cloud point extraction (RS-CPE) was established for nickel preconcentration and determination prior to its determination by flame atomic absorption spectrometry. In this work, the traditional CPE pattern was changed and greatly simplified in order to be applicable in metal extraction and detection. This method was accomplished in room temperature in 1 min. Non-ionic surfactant Triton X-114 was used as extractant. Octanol worked as cloud point revulsant and synergic reagent. The various parameters affecting the extraction and preconcentration of nickel such as sample pH, 2,2'-Furildioxime concentration, amounts of octanol, amounts of Triton X-114, type of diluting solvent, extraction time, and ionic strength were investigated and optimized. Under optimal conditions, the calibration curve showed an excellent linearity in the concentration range of 2-200 MUg L(-1), and the limit of detection was 0.6 MUg L(-1) for nickel. The developed method was successfully applied for the determination of nickel in food and water samples. The results showed that, the proposed method can be used as a cheap, rapid, and efficient method for the extraction and preconcentration of nickel from real samples. PMID- 26857257 TI - Evaluation of the maternal and fetal risk factors associated with neonatal care unit hospitalization time. AB - OBJECTIVE: To evaluate maternal and neonatal risk factors associated with the length of hospital stay in the neonatal intensive care unit (NICU). MATERIAL AND METHOD: This retrospective observational study was based on 3607 newborns who were admitted to the NICU of a tertiary teaching hospital from January 2012 through December 2014. Known obstetric risk factors associated with duration of hospitalization in NICUs were assessed including intrauterine growth restriction, maternal diabetes, oligohydramnios, chorioamnionitis, premeture rupture of membranes, preeclampsia, congenital malformations, neonatal sepsis, premature retinopathy, intracranial bleeding, necrotizing enterocolitis, meconium aspiration, maternal hypertension, fetal congenital cardiac malformations, congenital metabolic diseases, congenital hypothyroidism, pneumonia, pulmonary hypertension, bronchopulmonary dysplasia, pneumothorax and respiratory distress syndrome. RESULTS: Gestational age (beta coefficient: -0.244, p<0.001) and birth weight (beta coefficient: -0.237, p<0.001) were significant confounders for duration of hospitalization in newborns. CONCLUSION: Gestational age and the birth weight were the most important confounders for duration of hospitalization. Neonate care in developing countries would further benefit from additional large population-based long-term studies with broad parameters. PMID- 26857258 TI - [Standard therapy of tuberculosis]. AB - Based on the results of studies from the 1960s-1980s the current four drug combination therapy was established as standard or short course tuberculosis therapy worldwide. The regional epidemiology and the often unique conditions within a national health system create the need for specific adjustments. Over the last years these were realized by the German central committee against tuberculosis (DZK) in the recommendations for tuberculosis therapy. Because of the recent development of migration into Germany from countries with higher tuberculosis incidences an increase in tuberculosis cases is to be expected. The expected increase in tuberculosis cases will lead to more contact with tuberculosis patients even in the outpatient setting. New S2k guidelines guided by the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF) for the treatment of tuberculosis for children and adults are under development. Before the release of the comprehensive guidelines, practical evidence for the diagnosis and treatment of uncomplicated tuberculosis is summarized in this document to meet the challenges of the recent developments. PMID- 26857259 TI - Selective plasmon-driven catalysis for para-nitroaniline in aqueous environments. AB - The plasmon-driven oxidation of amine (-NH2) groups and the reduction of nitro ( NO2) groups on a nanostructured metal surface in an aqueous environment have been reported experimentally and theoretically. The question of which process occurs first in the aqueous environment is an interesting question in the field of plasmon-related photochemistry. Para-nitroaniline (PNA), with both nitro (-NO2) and amine (-NH2) groups, is the best candidate for studying the priority of the plasmon-driven oxidation and the reduction reactions in an aqueous environment. Using surface-enhanced Raman scattering (SERS) spectroscopy, our experimental results and theoretical simulations reveal that PNA is selectively catalyzed to 4,4'-diaminoazobenzene (DAAB) through the plasmon-assisted dimerization of the nitro (-NO2) group into an azo group in an aqueous environment. This indicates that the plasmon-driven reduction of the nitro (-NO2) group clearly occurs before the oxidation of the amine (-NH2) group in an aqueous environment. The plasmon driven reduction of PNA to DAAB is a selective surface catalytic reduced reaction in aqueous environment. PMID- 26857261 TI - Synthesis of alpha,omega-polyfluorinated alpha-amino acid derivatives and delta,delta-difluoronorvaline. AB - Intending to synthesize omega,omega-difluoroalkyl amino acid derivatives by oxidative desulfurization-fluorination reactions of suitable arylthio-2 phthalimido butanoates and pentanoates, in addition to small amounts of the target products, mainly alpha,omega-polyfluorinated amino acid derivatives were formed by additional sulfur-assisted alpha-fluorination. This novel structural motif was verified spectroscopically as well as by X-ray analysis. A plausible mechanism of formation is suggested. Using a different approach, delta,delta difluoronorvaline hydrochloride was synthesized with at least 36% enantiomeric excess via deoxofluorination of the corresponding aldehyde. PMID- 26857260 TI - Ongoing Response in BRAF V600E-Mutant Melanoma After Cessation of Intermittent Vemurafenib Therapy: A Case Report. AB - The selective BRAF inhibitors vemurafenib and dabrafenib yield high response rates and improved overall survival in patients with BRAF V600E-mutant metastatic melanoma. Treatment traditionally continues until disease progression or the development of unacceptable toxicity. Acquired drug resistance and toxicity are key challenges with the use of these drugs. Resistance to vemurafenib usually develops within 6-8 months. Management of drug toxicity typically involves stopping vemurafenib until resolution, before restarting at a lower dose, or permanently ceasing vemurafenib therapy. We have recently considered whether intermittent dosing could be used as an alternative to dose reduction/termination in the management of vemurafenib toxicity. One patient treated with intermittent vemurafenib was an 89-year-old woman with metastatic melanoma, who initially showed a good response to continuous dosing. Recurrent toxicity meant that the continuous vemurafenib dosage was repeatedly ceased before restarting at a lower dose. Ten months after vemurafenib was first begun, an intermittent dosing regimen was introduced in an attempt to control toxicity. This continued for 2 months, before cessation due to continued unacceptable toxicity. A further 24 months later, the patient remains fit and well in complete clinical remission, with no recurrence of her previous melanoma and no new primary malignancies. To the best of our knowledge, a continued response after the cessation of selective BRAF inhibitors has never before been described in melanoma. Induction of an immune response and/or epigenetic changes could explain continued disease response after cessation of vemurafenib therapy. Care should be taken when extrapolating the findings from the continued response after vemurafenib cessation to other tumour types. We recommend the collection and analysis of data to investigate the clinical responses seen after cessation of vemurafenib due to intolerable toxicities, which could help further explain vemurafenib's mechanism of action. PMID- 26857262 TI - Distinct Subtypes of Gastric Cancer Defined by Molecular Characterization Include Novel Mutational Signatures with Prognostic Capability. AB - Gastric cancer is not a single disease, and its subtype classification is still evolving. Next-generation sequencing studies have identified novel genetic drivers of gastric cancer, but their use as molecular classifiers or prognostic markers of disease outcome has yet to be established. In this study, we integrated somatic mutational profiles and clinicopathologic information from 544 gastric cancer patients from previous genomic studies to identify significantly mutated genes (SMG) with prognostic relevance. Gastric cancer patients were classified into regular (86.8%) and hypermutated (13.2%) subtypes based on mutation burden. Notably, TpCpW mutations occurred significantly more frequently in regular, but not hypermutated, gastric cancers, where they were associated with APOBEC expression. In the former group, six previously unreported (XIRP2, NBEA, COL14A1, CNBD1, ITGAV, and AKAP6) and 12 recurrent mutated genes exhibited high mutation prevalence (>=3.0%) and an unexpectedly higher incidence of nonsynonymous mutations. We also identified two molecular subtypes of regular mutated gastric cancer that were associated with distinct prognostic outcomes, independently of disease staging, as confirmed in a distinct patient cohort by targeted capture sequencing. Finally, in diffuse-type gastric cancer, CDH1 mutation was found to be associated with shortened patient survival, independently of disease staging. Overall, our work identified previously unreported SMGs and a mutation signature predictive of patient survival in newly classified subtypes of gastric cancer, offering opportunities to stratify patients into optimal treatment plans based on molecular subtyping. Cancer Res; 76(7); 1724-32. (c)2016 AACR. PMID- 26857263 TI - A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver. AB - Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFalpha, IL1beta, IL6, and IFNgamma protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698 704. (c)2016 AACR. PMID- 26857264 TI - Genomic Landscape of Somatic Alterations in Esophageal Squamous Cell Carcinoma and Gastric Cancer. AB - Gastric cancer and esophageal cancer are the second and sixth leading causes of cancer-related death worldwide. Multiple genomic alterations underlying gastric cancer and esophageal squamous cell carcinoma (ESCC) have been identified, but the full spectrum of genomic structural variations and mutations have yet to be uncovered. Here, we report the results of whole-genome sequencing of 30 samples comprising tumor and blood from 15 patients, four of whom presented with ESCC, seven with gastric cardia adenocarcinoma (GCA), and four with gastric noncardia adenocarcinoma. Analyses revealed that an A>C mutation was common in GCA, and in addition to the preferential nucleotide sequence of A located 5 prime to the mutation as noted in previous studies, we found enrichment of T in the 5 prime base. The A>C mutations in GCA suggested that oxidation of guanine may be a potential mechanism underlying cancer mutagenesis. Furthermore, we identified genes with mutations in gastric cancer and ESCC, including well-known cancer genes, TP53, JAK3, BRCA2, FGF2, FBXW7, MSH3, PTCH, NF1, ERBB2, and CHEK2, and potentially novel cancer-associated genes, KISS1R, AMH, MNX1, WNK2, and PRKRIR Finally, we identified recurrent chromosome alterations in at least 30% of tumors in genes, including MACROD2, FHIT, and PARK2 that were often intragenic deletions. These structural alterations were validated using the The Cancer Genome Atlas dataset. Our studies provide new insights into understanding the genomic landscape, genome instability, and mutation profile underlying gastric cancer and ESCC development. Cancer Res; 76(7); 1714-23. (c)2016 AACR. PMID- 26857265 TI - Dynamic monitoring of cell mechanical properties using profile microindentation. AB - We have developed a simple and relatively inexpensive system to visualize adherent cells in profile while measuring their mechanical properties using microindentation. The setup allows simultaneous control of cell microenvironment by introducing a micropipette for the delivery of soluble factors or other cell types. We validate this technique against atomic force microscopy measurements and, as a proof of concept, measure the viscoelastic properties of vascular endothelial cells in terms of an apparent stiffness and a dimensionless parameter that describes stress relaxation. Furthermore, we use this technique to monitor the time evolution of these mechanical properties as the cells' actin is depolymerized using cytochalasin-D. PMID- 26857266 TI - Multiple scattering induced negative refraction of matter waves. AB - Starting from fundamental multiple scattering theory it is shown that negative refraction indices are feasible for matter waves passing a well-defined ensemble of scatterers. A simple approach to this topic is presented and explicit examples for systems of scatterers in 1D and 3D are stated that imply negative refraction for a generic incoming quantum wave packet. Essential features of the effective scattering field, densities and frequency spectrum of scatterers are considered. Additionally it is shown that negative refraction indices allow perfect transmission of the wave passing the ensemble of scatterers. Finally the concept of the superlens is discussed, since it is based on negative refraction and can be extended to matter waves utilizing the observations presented in this paper which thus paves the way to 'untouchable' quantum systems in analogy to cloaking devices for electromagnetic waves. PMID- 26857267 TI - Regorafenib Also Can Cause Osteonecrosis of the Jaw. PMID- 26857268 TI - Introduction to 'All roads take to the brain: neural control of energy homeostasis in health and disease'. PMID- 26857269 TI - Childhood obesity: evidence for distinct early and late environmental determinants a 12-year longitudinal cohort study (EarlyBird 62). PMID- 26857270 TI - Modified Ashworth scale and spasm frequency score in spinal cord injury: reliability and correlation. AB - STUDY DESIGN: Intra- and inter-rater reliability study. OBJECTIVES: To assess intra- and inter-rater reliability of the Modified Ashworth Scale (MAS) and Spasm Frequency Score (SFS) in lower extremities in a population of spinal cord-injured persons, as well as correlations between the two scales. SETTING: Clinic for Spinal Cord Injuries, Rigshospitalet, Hornbaek, Denmark. METHODS: Thirty-one persons participated in the study and were tested four times in total with MAS and SFS by three experienced raters. Cohen's kappa (kappa), simple and quadratic weighted (nominal and ordinal scale level of measurement), was used as a measure of reliability and Spearman's rank correlation coefficient for correlation between MAS and SFS. RESULTS: Neurological level ranged from C2 to L2 and American Spinal Injury Association impairment scale A to D. Time since injury was (mean+/-s.d.) 3.4+/-6.5 years. Age was 48.3+/-20.2 years. Cause of injury was traumatic in 55% and non-traumatic for 45% of the participants. Antispastic medication was used by 61%. MAS showed intra-rater kappasimple=-0.11 to 0.46 and kappaweighted=-0.11 to 0.83. Inter-rater kappasimple=-0.06 to 0.32 and kappaweighted=0.08 to 0.74. SFS showed intra-rater kappaweighted=0.94 and inter rater kappaweighted=0.93. Correlation between MAS and SFS showed non-significant correlation coefficients from-0.11 to 0.90. CONCLUSION: Reliability of MAS is highly affected by the weighting scheme. With a weighted-kappa it was overall reliable and simple-kappa overall unreliability. Repeated tests should always be performed by the same rater and in a very standardized manner. SFS was found reliable. MAS and SFS are poorly correlated, and ratings were inversely distributed and suggest that it assesses different aspects of spasticity. PMID- 26857271 TI - The influence of orthosis options on walking parameters in spinal cord-injured patients: a literature review. AB - OBJECTIVE: Orthoses for various joints sections are considered to greatly influence the gait function and energy expenditure in spinal cord-injured (SCI) patients. The aim of this review was to determine the influence of orthoses characteristics and options on the improvement of walking in patients with SCI. METHODS: A search was performed using the Population Intervention Comparison Outcome (PICO) method, based on selected keywords; studies were identified electronically in the Science Direct, Google Scholar, Scopus, Web of Knowledge and PubMed databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method was used to report the results. Assessment of the quality of all articles was performed based on the Physiotherapy Evidence Database (PEDro scale). RESULTS: Twelve studies evaluated the effects of different hip joint options on walking parameters and energy expenditure. Five studies investigated the role of knee joint options on gait parameters and compensatory trunk motion. Only five studies analyzed modified ankle joints on gait parameters in SCI patients. Nine studies analyzed gait parameters in SCI patients as powered orthoses and exoskeleton. These studies had a low level of evidence according to the PEDro score (2/10). CONCLUSION: The various joint types of orthoses appear to be critical in the improvement of walking in patients with SCI. In particular, 'user friendly' orthoses that support the related structure such as the hip joint with a reciprocating mechanism, activated knee joint and movable ankle joint with dorsiflexion assist enable SCI patients to optimize their walking pattern when wearing an orthoses system. PMID- 26857272 TI - The influence of diet on nestling body condition of an apex predator: a multi biomarker approach. AB - Animal body condition refers to the health and physiological state of individuals, and multiple parameters have been proposed to quantify this key concept. Food intake is one of the main determinants of individual body condition and much debate has been generated on how diet relates to body condition. We investigated this relationship in free-living Bonelli's eagle (Aquila fasciata) nestlings sampled at two geographically distant populations in Spain. Nestlings' main prey consumption was estimated by isotopic analyses. A multi-biomarker approach, including morphometric and blood biochemical measures (i.e. hematocrit, plasma biochemistry and oxidative stress biomarkers), enabled us to integrate all the body condition measures taken. A greater consumption of a preferred prey [i.e. the European rabbit (Oryctolagus cuniculus)] improved nestling body condition, as indicated by lower levels of cholesterol in plasma, greater activity of enzymes mediating in protein catabolism, higher levels of tocopherol and glutathione, and less glutathione peroxidase activity, which also suggested lower degree of oxidative stress. On the other hand, increased diet diversity was positively correlated with higher levels of oxidized glutathione, which suggests that these nestlings had poorer body condition than those with a higher frequency of preferred prey consumption. Several factors other than diet [i.e. altitude of nesting areas, nestling sex and age, sampling time (before or after midday) and recent food ingestion] had an effect on certain body condition measures. Our study reveals a measurable effect of diet on a predator's body condition and demonstrates the importance of considering the potential influence of multiple intrinsic and extrinsic factors when assessing animal body condition. PMID- 26857273 TI - Environmental and cortisol-mediated control of Ca(2+) uptake in tilapia (Oreochromis mossambicus). AB - Ca(2+) is a vital element for many physiological processes in vertebrates, including teleosts, which live in aquatic environments and acquire Ca(2+) from their surroundings. Ionocytes within the adult gills or larval skin are critical sites for transcellular Ca(2+) uptake in teleosts. The ionocytes of zebrafish were found to contain transcellular Ca(2+) transporters, epithelial Ca(2+) channel (ECaC), plasma membrane Ca(2+)-ATPase 2 (PMCA2), and Na(+)/Ca(2+) exchanger 1b (NCX1b), providing information about the molecular mechanism of transcellular Ca(2+) transports mediated by ionocytes in fish. However, more evidence is required to establish whether or not a similar mechanism of transcellular Ca(2+) transport also exists in others teleosts. In the present study, ecac, pmca2, and ncx1 were found to be expressed in the branchial ionocytes of tilapia, thereby providing further support for the mechanism of transcellular Ca(2+) transport through ionocytes previously proposed for zebrafish. In addition, we also reveal that low Ca(2+) water treatment of tilapia stimulates Ca(2+) uptake and expression of ecac and cyp11b (the latter encodes a cortisol-synthesis enzyme). Treatment of tilapia with exogenous cortisol (20 mg/l) enhanced both Ca(2+) influx and ecac expression. Therefore, increased cyp11b expression is suggested to enhance Ca(2+) uptake capacity in tilapia exposed to low Ca(2+) water. Furthermore, the application of cortisol receptor antagonists revealed that cortisol may regulate Ca(2+) uptake through glucocorticoid and/or mineralocorticoid receptor (GR and/or MR) in tilapia. Taken together, the data suggest that cortisol may activate GR and/or MR to execute its hypercalcemic action by stimulating ecac expression in tilapia. PMID- 26857274 TI - The transition from water-breathing to air-breathing is associated with a shift in ion uptake from gills to gut: a study of two closely related erythrinid teleosts, Hoplerythrinus unitaeniatus and Hoplias malabaricus. AB - The evolutionary transition from water-breathing to air-breathing involved not only a change in function of the organs of respiratory gas exchange and N-waste excretion, but also in the organs of ion uptake from the environment. A combination of in vivo and in vitro techniques was used to look at the relative importance of the gills versus the gut in Na(+), Cl(-), and K(+) balance in two closely related erythrinid species: a facultative air-breather, the jeju (Hoplerythrinus unitaeniatus) and an obligate water-breather, the traira (Hoplias malabaricus). The jeju has a well-vascularized physostomous swimbladder, while that in the traira is poorly vascularized, but the gills are much larger. Both species are native to the Amazon and are common in the ion-poor, acidic blackwaters of the Rio Negro. Under fasting conditions, the traira was able to maintain positive net Na(+) and Cl(-) balance in this water, and only slightly negative net K(+) balance. However, the jeju was in negative net balance for all three ions and had lower plasma Na(+) and Cl(-) concentrations, despite exhibiting higher branchial Na(+), K(+)ATPase and v-type H(+)ATPase activities. In the intestine, activities of these same enzymes were also higher in the jeju, and in vitro measurements of net area-specific rates of Na(+), Cl(-), and K(+) absorption, as well as the overall intestinal absorption capacities for these three ions, were far greater than in the traira. When acutely exposed to disturbances in water O2 levels (severe hypoxia ~15% or hyperoxia ~420% saturation), gill ionoregulation was greatly perturbed in the traira but less affected in the jeju, which could "escape" the stressor by voluntarily air breathing. We suggest that a shift of ionoregulatory capacity from the gills to the gut may have occurred in the evolutionary transition to air-breathing in jeju, and in consequence branchial ionoregulation, while less powerful, is also less impacted by variations in water O2 levels. PMID- 26857275 TI - Examining Variation in Hospice Visits by Professional Staff in the Last 2 Days of Life. AB - IMPORTANCE: In the final days of life, symptoms are exacerbated and often families need both education and emotional support from hospice professional staff. The Medicare Hospice Benefit provides a per-diem payment with no requirements on the frequency of patient visits. OBJECTIVE: To examine individual characteristics, hospice program, and geographic variation in hospice visits by professional staff during the last 2 days of life. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of 661 557 Medicare hospice beneficiaries included all patients who died in federal fiscal year 2014 (October 1, 2013-September 30, 2014) in hospice services while receiving routine home care in the last 2 days of life. Data analysis was conducted from March 9 to August 25, 2015. MAIN OUTCOMES AND MEASURES: Medicare regulations require that hospice care centers report daily the frequency and duration of patient visits by professional staff, as well as the type of hospice staff who conduct these visits. We examined visit variation by hospice professional staff (physician, nursing staff, and social worker) during the last 2 days of life using a multivariable logistic model adjusting for decedent and hospice program characteristics. RESULTS: Of the 661 557 patients in the study, 81 478 (12.3%) received no professional staff visits in the last 2 days of life. State variation ranged from 590 of 15 399 patients (3.8%) in Wisconsin to 97 of 492 patients (19.7%) in Alaska, and hospice program interquartile variation ranged from 3.2% (25th percentile) to 19.5% (75th percentile). Black patients were less likely to have any visits than were white patients (7352 of 48 221 [15.2%] vs 70 365 of 585 377 [12.0%]; adjusted odds ratio, 1.30; 95% CI, 1.24-1.37). Those dying in a nursing home were 1.74 times less likely to have any visits than those dying at home (30 880 of 186 649 [16.5%] vs 40 973 of 386 654 [10.6%]; 95% CI, 1.62-1.88). Those dying on a Sunday were 3.35 times less likely to have a visit compared with persons dying on a Tuesday (19 519 of 95 979 [20.3%] vs 6784 of 92 127 [7.4%]; 95% CI, 3.17-3.55). CONCLUSIONS AND RELEVANCE: Hospice visits in the last 2 days of life by professional staff vary by race, hospice program, and geographic region of the country. Visits were less likely when the Medicare beneficiary was black, dying on a Sunday, and receiving care in a nursing home. PMID- 26857277 TI - Immunization Policy and the Importance of Sustainable Vaccine Pricing. PMID- 26857276 TI - Genome stability of Propionibacterium acnes: a comprehensive study of indels and homopolymeric tracts. AB - We present a species-wide comparative analysis of 90 genomes of Propionibacterium acnes that represent the known diversity of the species. Our results are augmented by six high-quality genomes and a manual investigation of all gene sized indels found in the strains. Overall, the order of genes is conserved throughout the species. A public sybil database for easy comparative analysis of the 90 genomes was established. The analysis of indels revealed a total of 66 loci of non-core genes that correlate with phylogenetic clades. No gene was strain-specific in agreement with our conclusion that the P. acnes pan-genome is closed. An exhaustive search for homopolymeric tracts (HPTs) identified a total of 54 variable-length HPTs almost exclusively of guanine/cytosines located between genes or affecting the reading frame of genes. The repeat variation was consistent with phylogenetic clades suggesting slow accumulation over time rather than active modification. By transcriptome analysis we demonstrate how an HPT variation can affect the gene expression levels. Selected cases of both indels and HPTs are described. The catalogued data and the public P. acnes Sybil database provide a solid foundation for generating hypotheses and facilitate comparative genetic analyses in future P. acnes research. PMID- 26857279 TI - Clinical impact of circulating microRNAs as blood-based marker in childhood acute lymphoblastic leukemia. AB - Aberrant microRNA (miRNA) expression participates in childhood acute lymphoblastic leukemia (ALL). This study aimed to investigate the expression of miRNA-100, miRNA-196a, and miRNA-146a among childhood ALL and study their correlation with other hematological parameters and different phenotypes. Peripheral blood mononuclear cells (PMNCs) were obtained from 85 childhood ALL and 25 healthy children for the detection of miRNA expression using quantitative real-time PCR. Significant higher median levels were reported for ALL compared to control children. The diagnostic efficacy for miRNA-146a was superior as both sensitivity and specificity were absolute. A significant correlation was observed between higher expression of miRNA-100 and lower platelet and lymphocyte counts; high expression of miRNA-146a showed significant correlation with low total leukocyte count (TLC) and lymphocyte counts. Significant relation was reported between studied miRNAs and different phenotyping. miRNA-100, miRNA-196a, and miRNA-146a have significant role in childhood ALL leukemogenesis, and they may be useful as biological diagnostic molecular markers. PMID- 26857280 TI - Differential expression of PDGFRB and EGFR in microvascular proliferation in glioblastoma. AB - Glioblastoma (GBM) is the highly malignant glioma and exhibits microvascular proliferation. PCR mRNA arrays and immunohistochemical stains on tissue microarray demonstrated that the expression level of PDGFRB in GBM microvascular proliferation was significantly higher than that in GBM tumor cells while the expression level of EGFR was lower in microvascular proliferation than in GBM tumor cells. PDGFRB protein was selectively expressed in pericytes in GBM microvascular proliferation. By analyzing The Cancer Genome Atlas (TCGA) datasets for GBM, it was found that genomic DNA alterations were the main reason for the high expression of EGFR in GBM tumor cells. Our miRNA microarray data showed that microRNAs (miRNAs) (miR-193b-3p, miR-518b, miR-520f-3p, and miR-506-5p) targeting PDGFRB were downregulated in microvascular proliferation, which might be the most likely reason for the high expression of PDGFRB in GBM microvascular proliferation. The increase of several miRNAs (miR-133b, miR-30b-3p, miR-145-5p, and miR-146a-5p) targeting EGFR in GBM microvascular proliferation was one of the reasons for the lack of expression of EGFR in GBM microvascular proliferation. These findings implicated that miRNAs, such as miR-506, miR-133b, miR-145, and miR-146a, that target PDGFRB or EGFR, might be potential therapeutic agents for GBM. A new generation of targeted therapeutic agents against both EGFR and PDGFRB might be developed in the future. PMID- 26857281 TI - Overexpression of SphK1 enhances cell proliferation and invasion in triple negative breast cancer via the PI3K/AKT signaling pathway. AB - Sphingosine kinase 1 (SphK1) expression is elevated in various cancers and is associated with shorter survival times for patients. However, the molecular mechanism of SphK1 up-regulation in triple-negative breast cancer (TNBC) remains unclear. In this study, we assayed the expression level of SphK1 in TNBC tissues by qRT-PCR and immunohistochemistry. The level of S1P was quantified by ELISA in the serum of TNBC patients. Our results found that the levels of SphK1 and S1P were significantly increased in TNBC patients compared with normal control. Furthermore, knockdown of SphK1 with siRNA decreased TNBC cell proliferation and inhibited cell migration/invasion. These data suggest that SphK1 has an important role in TNBC and presents an attractive therapeutic target for the treatment for TNBC. PMID- 26857282 TI - The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells. AB - The contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This in vitro study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities. pMSC multipotency was confirmed by successful differentiation into cells of both the osteogenic and endothelial lineages, as demonstrated by positive Alizarin Red S staining and Ac-LDL uptake. pMSC differentiation in the presence of non-cytotoxic BP concentrations showed that nitrogen containing BPs had a significant inhibitory effect on cell migration and endothelial marker gene expression, as well as compromised endothelial differentiation as demonstrated using von Willebrand factor immunofluorescence staining and tube formation assay. This in vitro study demonstrated that at non cytotoxic levels, nitrogen-containing BPs inhibit differentiation of pMSCs into cells of an endothelial lineage and affect the downstream functional capability of these cells supporting a multi-modal effect of BPs on angiogenesis as pathogenic mechanism contributing to bone healing disorders such as bisphosphonate related osteonecrosis of the jaws (BRONJ). PMID- 26857284 TI - Can postpartum maternal urinary iodine be used to estimate iodine nutrition status of newborns? AB - I deficiency can lead to detrimental effects, particularly in neonates and young infants. The aim of this study was to explore whether postpartum maternal urinary I can be used to estimate the I status of newborns. In this cross-sectional study conducted in Tehran, lactating mothers and newborns, within 3-5 d postpartum, were randomly selected. Urine samples were collected from each mother and newborn, and a heel-prick blood sample was obtained from all newborns as part of the routine national newborn screening programme. According to the WHO criteria, median urinary I concentration (UIC) 5 mIU/l was considered as I insufficiency. A total of 147 postpartum women and neonates, aged 27.8 (SD 5.3) years and 4.2 (SD 0.6) d, respectively, completed this study. The median UIC was 68.0 (interquartile range (IQR) 39.4-133.5) and 212.5 (IQR 92.3-307.3) ug/l in postpartum mothers and newborns, respectively. The median neonatal TSH was 1.00 (IQR 0.50-1.70) mIU/l. There was no significant difference in the neonatal UIC and TSH of infants whose mothers had deficient and sufficient urinary I. In the multiple linear regression, neonatal UIC value was associated with maternal urinary I (P=0.048) and parity (P=0.039); a significant association was observed between neonatal TSH and infant sex (P=0.038) and birth weight (P=0.049). The findings of our study demonstrate that, despite postpartum mothers being mildly I deficient, I status of their infants was adequate as assessed by UIC and TSH values. It seems factors other than maternal urinary I may influence the I status in newborns. PMID- 26857283 TI - Immunotherapy in Chronic Lymphocytic Leukaemia (CLL). AB - Chronic lymphocytic leukaemia (CLL) is well known to generate impaired immune responses in the host, with the malignant clone residing in well-vascularized tissues and circulating in peripheral blood but also in close proximity to effector cells that are capable, if activated appropriately, of eliciting a cytotoxic response. These, combined with the fact that this is frequently a condition affecting older patients with co-morbidities often unfit for many "traditional" cytotoxic agents with their significant associated toxicities, make CLL an ideal candidate for the development of immunotherapy. The impressive results seen with the addition of a monoclonal antibody, rituximab, to a chemotherapy backbone, for example, is testament to how effective harnessing an immune-mediated response in CLL can be. This review serves to outline the available arsenal of immunotherapies-past and present-demonstrated to have potential in CLL with some perspectives on how the landscape in this disease may evolve in the future. PMID- 26857286 TI - Silver Ink Formulations for Sinter-free Printing of Conductive Films. AB - Inkjet printing offers an attractive method for the deposition of metal interconnects in electronic systems and enables a low-cost, environmentally friendly route to manufacture. However, virtually all current metal inkjet processes require post-deposition sintering treatments to achieve the optimum electrical conductivity, because the growth mechanism involves coalescence of discrete nanoparticles. A manufacturing process that reduces the number of steps by directly printing silver, removing the need to sinter the printed metal, would be highly advantageous. Here we describe a, sinter-free process that results in the direct printing of crystalline silver. This process exploits the chemistries developed for Atomic Layer Deposition (ALD), to form the basis of a new ink formulation, which we term; Reactive Organometallic inks (ROM). These ROM ink formulations are capable of depositing low temperature, high conductivity metal films, without the need for subsequent sintering treatments. To reduce the temperature for direct formation of metallic Ag, we have added an alcohol as a catalytic reducing agent to dissociate the organometallic component. Silver films printed from our novel ROM ink, on a glass substrate at 120 degrees C, are electrically conductive with a typical resistivity as low as 39.2% that of bulk silver, without the need for sintering. PMID- 26857285 TI - Impact of low-dose rabbit anti-thymocyte globulin in unrelated hematopoietic stem cell transplantation. AB - We retrospectively evaluated the outcome of administering low-dose rabbit anti thymocyte globulin (thymoglobulin: ATG-T) to 219 patients (ATG-T group, n = 30; no-ATG-T group, n = 189) who received an initial unrelated hematopoietic stem cell transplantation (uHSCT). The median total dose of ATG-T was 1.5 mg/kg. There was no significant difference in the cumulative incidences of grade II-IV (42 vs. 38 %, P = 0.87) and grade III-IV (5 vs. 7 %, P = 0.52) acute GVHD. In patients who received uHSCT from a donor with at least one HLA allele mismatch, the cumulative incidence of extensive chronic GVHD was significantly lower in the ATG T group than that in the no-ATG-T group (13 vs. 44 %, P = 0.02). No patient in the ATG-T group developed chronic lung dysfunction. The probabilities of 1-year, GVHD-free/relapse-free survival (GRFS) were 61 % in the ATG-T group and 35 % in the no-ATG-T group (P = 0.02). Patients in the ATG-T group discontinued immunosuppressive drugs significantly earlier than those in the no-ATG-T group (P < 0.01). The use of low-dose ATG-T did not increase the incidence of severe infectious disease. The use of low-dose ATG-T in patients who received uHSCT was associated with a superior GRFS, reflecting the reduced incidence of severe/persistent GVHD without compromising overall survival. PMID- 26857287 TI - "It's Like Backing up Science with Scripture": Lessons Learned from the Implementation of HeartSmarts, a Faith-Based Cardiovascular Disease Health Education Program. AB - African-Americans are disproportionately impacted by cardiovascular disease (CVD). Faith-based institutions provide a non-traditional route for health education targeted at African-Americans. This paper describes HeartSmarts, a faith-based CVD education program. Evidence-based literature was used to develop a curriculum, which was tailored by integrating biblical scripture representing aspects of health behaviors. Eighteen church peer-educators were recruited to participate in a 12-week training. They then disseminated the faith-based curriculum to members of their congregations. There were 199 participants of which 137 provided feedback via open-ended surveys indicating that HeartSmarts was well accepted and effective for disseminating CVD health messages while engaging spirituality. PMID- 26857288 TI - IMAGING DIAGNOSIS-NUCLEAR SCINTIGRAPHIC, RADIOLOGICAL, AND PATHOLOGIC CHARACTERISTICS OF METASTATIC PILOMATRICOMA IN A DOG. AB - A 6-year-old castrated Goldendoodle dog was presented for left-sided lameness of 3 weeks' duration. Focal, moderate to marked increased 99m Tc-methylene diphosphonate (99m Tc-MDP) uptake was detected in the right caudal lung lobe, caudal angle of the left scapula, and the distal aspect of the left femur with whole body bone phase scintigraphy. Radiographs identified a well-circumscribed, oval-shaped soft tissue opaque mass in the right caudal lung lobe; a suspect oval shaped osteolytic lesion in the proximal third of the left scapula; and an osteolytic lesion in the distal aspect of the left femur. Metastatic pilomatricoma was confirmed histologically at all three sites. PMID- 26857289 TI - Prediction of reduction in aggressive behaviour of growing pigs using skin lesion traits as selection criteria. AB - Aggression at regrouping is a common issue in pig farming. Skin lesions are genetically and phenotypically correlated with aggression and have been shown to have a significant heritable component. This study predicts the magnitude of reduction in complex aggressive behavioural traits when using lesion numbers on different body regions at two different time points as selection criteria, to identify the optimum skin lesion trait for selection purposes. In total, 1146 pigs were mixed into new social groups, and skin lesions were counted 24 h (SL24h) and 3 weeks (SL3wk) post-mixing, on the anterior, centre and posterior regions of the body. An animal model was used to estimate genetic parameters for skin lesion traits and 14 aggressive behavioural traits. Estimated breeding values (EBVs) and phenotypic values were scaled and standardised to allow direct comparison across multiple traits. Individuals with SL24h and SL3wk EBVs in the least aggressive 10% of the population were compared with the population mean to predict the expected genetic and phenotypic response in aggressive behaviour to selection. At mixing, selection for low anterior lesions was predicted to affect substantially more behavioural traits of aggressiveness than lesions obtained on other body parts, with EBVs between -0.21 and -1.17 SD below the population mean. Individuals with low central SL24h EBVs also had low EBVs for aggressive traits ( 0.33 to -0.55). Individuals with high SL3wk EBVs had low EBVs for aggression at mixing (between -0.24 and -0.53 SD below the population mean), although this was predicted to affect fewer traits than selection against SL24h. These results suggest that selection against anterior SL24h would result in the greatest genetic and phenotypic reduction in aggressive behaviour recorded at mixing. Selection for increased SL3wk was predicted to reduce aggression at mixing; however, current understanding about aggressive behaviour under stable social conditions is insufficient to recommend using this trait for selection purposes. PMID- 26857291 TI - Polymorphisms associated with four reproductive traits have no adverse effects on meat traits in Japanese Black cattle. PMID- 26857290 TI - Penetration of an artificial arterial thromboembolism in a live animal using an intravascular therapeutic microrobot system. AB - The biomedical applications of wireless robots are an active area of study. In addition to moving to a target lesion, wireless locomotive robots can deliver a therapeutic drug for a specific disease. Thus, they hold great potential as therapeutic devices in blood vessel diseases, such as thrombi and occlusions, and in other diseases, such as cancer and inflammation. During a percutaneous coronary intervention (PCI), surgeons wear a heavy shielding cloth. However, they cannot escape severe radiation exposure owing to unstable shielding. They may also suffer from joint pains because of the weight of the shielding cloth. In addition, the catheters in PCIs are controlled by the surgeon's hand. Thus, they lack steering ability. A new intravascular therapeutic system is needed to address these problems in conventional PCIs. We developed an intravascular therapeutic microrobot system (ITMS) using an electromagnetic actuation (EMA) system with bi-plane X-ray devices that can remotely control a robot in blood vessels. Using this proposed ITMS, we demonstrated the locomotion of the robot in abdominal and iliac arteries of a live pig by the master-slave method. After producing an arterial thromboembolism in a live pig in a partial iliac artery, the robot moved to the target lesion and penetrated by specific motions (twisting and hammering) of the robot using the proposed ITMS. The results reveal that the proposed ITMS can realize stable locomotion (alignment and propulsion) of a robot in abdominal and iliac arteries of a live pig. This can be considered the first preclinical trial of the treatment of an artificial arterial thromboembolism by penetration of a blood clot. PMID- 26857292 TI - Glucocerebrosidase enzyme activity in GBA mutation Parkinson's disease. AB - Mutations in the glucocerebrosidase (GBA1) gene, the most common genetic contributor to Parkinson's disease (PD), are associated with an increased risk of PD in heterozygous and homozygous carriers. While glucocerebrosidase enzyme (GCase) activity is consistently low in Gaucher disease, there is a range of leukocyte GCase activity in healthy heterozygous GBA1 mutation carriers. To determine whether GCase activity may be a marker for PD with heterozygous GBA1 mutations (GBA1 mutation PD, GBA PD), GBA PD patients (n=15) were compared to PD patients without heterozygous GBA1 mutations (idiopathic PD; n=8), heterozygous GBA1 carriers without PD (asymptomatic carriers; n=4), and biallelic mutation carriers with PD (Gaucher disease with PD, GD1 PD; n=3) in a pilot study. GCase activity (nmol/mg protein/hour) in GD1 PD (median [interquartile range]; minimum maximum: 6.4 [5.7]; 5.3-11) was lower than that of GBA PD (16.0 [7.0]; 11-40) (p=0.01), while GCase activity in GBA PD was lower than idiopathic PD (28.5 [15.0]; 16-56) (p=0.01) and asymptomatic carriers (25.5 [2.5]; 23-27) (p=0.04). Therefore, GCase activity appears to be a possible marker of heterozygous GBA1 mutation PD, and larger studies are warranted. Prospective studies are also necessary to determine whether lower GCase activity precedes development of PD. PMID- 26857293 TI - The head that wears the crown: Henry VIII and traumatic brain injury. AB - Henry VIII of England is one of the most controversial figures in European history. He was born on 28 June 1491 as the second son of Henry VII and Elizabeth of York and became the heir to the English throne after his elder brother died prematurely. A contradictory picture of Henry's character emerges from history: the young Henry was a vigorous, generous and intelligent king who saw early military and naval successes. In contrast, in his later years he became cruel, petty and tyrannical. His political paranoia and military misjudgements are in direct contrast to his earlier successes and promise. Several hypotheses have been put forward regarding his transformation from a renaissance king to a later medieval tyrant, including endocrinopathies, psychiatric illnesses and traumatic brain injury. In this paper we examine the historical evidence linking the change in Henry's personality and health problems to traumatic brain injury. To our knowledge this is the first systematic neurological study of traumatic brain injury in Henry VIII. PMID- 26857294 TI - Endovascular therapies for malignant gliomas: Challenges and the future. AB - Malignant gliomas are very difficult tumors to treat, with few effective therapies, early progression and high rates of recurrence. Here we review the literature on malignant gliomas treated with endovascular therapy. Endovascular therapy for malignant gliomas falls into one of three categories: (1) neoadjuvant embolization and devascularization; (2) direct intra-arterial drug delivery; and (3) disruption of the blood-brain barrier for improved intra-arterial drug delivery. There is a range of therapeutic benefits based on the endovascular intervention used. Challenges remain for those who aim to treat malignant gliomas with an endovascular approach. Specifically, embolization is difficult to accomplish in the small vessels that feed into malignant gliomas, and intra arterial chemotherapy has yet to prove itself better than traditional intravenous chemotherapy. However, there exists promise in the therapeutic potential of intra arterial chemotherapy paired with disruption of the blood-brain barrier at tumor specific sites, and as such, continued research to optimize this approach is expected to yield benefit for patients with malignant gliomas. PMID- 26857295 TI - Hypoxia in health and disease. PMID- 26857296 TI - First Responder Accuracy Using SALT during Mass-casualty Incident Simulation. AB - INTRODUCTION: During mass-casualty incidents (MCIs), patient volume often overwhelms available Emergency Medical Services (EMS) personnel. First responders are expected to triage, treat, and transport patients in a timely fashion. If other responders could triage accurately, prehospital EMS resources could be focused more directly on patients that require immediate medical attention and transport. HYPOTHESIS: Triage accuracy, error patterns, and time to triage completion are similar between second-year primary care paramedic (PCP) and fire science (FS) students participating in a simulated MCI using the Sort, Assess, Life-saving interventions, Treatment/Transport (SALT) triage algorithm. METHODS: All students in the second-year PCP program and FS program at two separate community colleges were invited to participate in this study. Immediately following a 30-minute didactic session on SALT, participants were given a standardized briefing and asked to triage an eight-victim, mock MCI using SALT. The scenario consisted of a four-car motor vehicle collision with each victim portrayed by volunteer actors given appropriate moulage and symptom coaching for their pattern of injury. The total number and acuity of victims were unknown to participants prior to arrival to the mock scenario. RESULTS: Thirty-eight PCP and 29 FS students completed the simulation. Overall triage accuracy was 79.9% for PCP and 72.0% for FS (? 7.9%; 95% CI, 1.2-14.7) students. No significant difference was found between the groups regarding types of triage errors. Over triage, under-triage, and critical errors occurred in 10.2%, 7.6%, and 2.3% of PCP triage assignments, respectively. Fire science students had a similar pattern with 15.2% over-triaged, 8.7% under-triaged, and 4.3% critical errors. The median [IQR] time to triage completion for PCPs and FSs were 142.1 [52.6] seconds and 159.0 [40.5] seconds, respectively (P=.19; Mann-Whitney Test). CONCLUSIONS: Primary care paramedics performed MCI triage more accurately than FS students after brief SALT training, but no difference was found regarding types of error or time to triage completion. The clinical importance of this difference in triage accuracy likely is minimal, suggesting that fire services personnel could be considered for MCI triage depending on the availability of prehospital medical resources and appropriate training. PMID- 26857297 TI - The Combined Utility of a Brief Functional Measure and Performance-Based Screening Test for Case Finding of Cognitive Impairment in Primary Healthcare. AB - BACKGROUND: Use of a total risk score (TRS) based on vascular and sociodemographic risk factors has been recommended to identify patients at risk of cognitive impairment. Moreover, combining screening tests has been reported to improve positive predictive values (PPV) for case finding of cognitive impairment. OBJECTIVE: We investigated the utility of the conjunctive combination of the informant-based AD8 and the performance-based National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) 5-minute protocol for the detection of cognitive impairment, defined by a clinical dementia rating (CDR) score >=0.5, in patients at risk of cognitive impairment (TRS >=3). METHODS: Participants were recruited from 2 primary healthcare centers in Singapore and received the AD8, Montreal Cognitive Assessment, Mini-Mental State Examination, CDR, and a formal neuropsychological test battery. The scores for NINDS-CSN 5-minute protocol were extracted from the Montreal Cognitive Assessment items. Area under the receiver operating characteristics curve analyses were conducted to determine the discriminant indices of the screening instruments, the conjunctive combination (ie, screened positive on both tests), and the compensatory combination (ie, screened positive in either of or both tests). RESULTS: A total of 309 participants were recruited of whom 78.7% (n = 243) had CDR = 0 and 21.3% (n = 66) had CDR >=0.5. The conjunctive combination of AD8 and NINDS-CSN 5-minute protocol achieved excellent PPV and acceptable sensitivity (PPV 91.7%, sensitivity 73.3%). CONCLUSIONS: The conjunctive combination of the AD8 and NINDS-CSN 5-minute protocol is brief and accurate, and hence, suitable for case finding of cognitive impairment (CDR >=0.5) in patients screened positive on the TRS in primary healthcare centers. PMID- 26857298 TI - Nonpharmacologic Interventions to Prevent Pressure Ulcers in Older Patients: An Overview of Systematic Reviews (The Software ENgine for the Assessment and optimization of drug and non-drug Therapy in Older peRsons [SENATOR] Definition of Optimal Evidence-Based Non-drug Therapies in Older People [ONTOP] Series). AB - BACKGROUND: Pressure ulcers (PUs) are frequent in older patients, and the healing process is usually challenging, therefore, prevention should be the first strategic line in PU management. Nonpharmacologic interventions may play a role in the prevention of PUs in older people, but most systematic reviews (SRs) have not addressed this specific population using convincing outcome measures. OBJECTIVE: To summarize and critically appraise the evidence from SRs of the primary studies on nonpharmacologic interventions to prevent PUs in older patients. DESIGN: SR and meta-analysis of comparative studies. DATA SOURCES: PubMed, Cochrane Database of Systematic Reviews, EMBASE, and CINHAL (from inception to October 2013) were searched. A new search for updates in the Cochrane Database was launched in July 2014. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: SRs that included at least 1 comparative study evaluating any nonpharmacologic intervention to prevent PUs in older patients, in any healthcare setting, were selected. Any primary study with experimental design was then identified and included. DATA EXTRACTION: From each primary study, quality assessment was undertaken as specified by the Cochrane Collaboration and the Grading of Recommendations Assessment, Development and Evaluation working group. Interventions were identified and compared among different studies to explore the possibility of performing a meta-analysis, using the incidence of new pressure ulcers as the main outcome measure. RESULTS: One hundred ten SRs with 65 primary studies satisfied the inclusion criteria. The most frequent interventions explored in these trials were support surfaces (41 studies), repositioning (8), and nutrition interventions (5). High quality of evidence was not found for any intervention, mainly because of a high risk of bias and imprecision. There is moderate quality evidence to support the use of alternating pressure support mattresses over usual hospital mattresses in medical and surgical inpatients, low quality evidence to support constant low pressure devices and Australian medical sheepskin over usual mattresses, and very low quality evidence to support nutrition interventions in hospital settings. No recommendations on hydration, repositioning, standardized risk assessment, or multicomponent interventions can be done. CONCLUSIONS: In older patients at high risk to suffer PUs, high technology and low- technology support surfaces can significantly reduce the incidence of PUs. Nutrition intervention may also have a role in preventing PUs in hospital settings. More evidence is needed to support other recommendations, which is specially lacking for repositioning. PMID- 26857299 TI - [Pseudopneumothorax]. PMID- 26857300 TI - [Adjuvant medical treatment for patients with locoregional recurrence of breast cancer]. AB - There is 10-30% risk of developing isolated locoregional recurrence (ILRR) after mastectomy for primary breast cancer. Currently, there is no standard treatment for ILRR and therefore patients with ILRR cause an oncological task. This review investigates existing literature concerning relevant randomized trials of adjuvant medical treatment with chemotherapy, anti-hormonal and anti HER2 treatments for patients radically treated for ILRR. Certain groups of patients may benefit from adjuvant systemic treatment. However larger randomized trials are needed. PMID- 26857301 TI - [Primary effusion lymphoma is a rare cause of pleural effusion]. AB - Primary effusion lymphoma (PEL) is a rare form of extranodal non-Hodgkin lymphoma, which presents as an accumulation of lymphatic cells within a body cavity. It is classified as a human herpesvirus 8 (HHV-8)-positive lymphoma and is associated with HIV. The prognosis is poor. Cases of HHV-8-negative PEL have been described in immunocompetent patients. We report a case of an 86-year-old man diagnosed with HHV-8-negative PEL. Based on case reports he was treated with pleuracentesis and was still in complete remission one year later. PMID- 26857302 TI - [Effective pain relief of post-herpetic neuralgia with capsaicin patch]. AB - Topical 8% capsaicin is a recently approved treatment for post-herpetic neuralgia (PHN). Capsaicin works by causing extensive depolarization of nociceptive epidermal transient receptor potential cation channel V1-positive C-fibers leading to defunctionalization. In this case story a 51-year-old male patient, who was suffering from severe PHN pain and associated allodynia, experienced drastic pain relief upon treatment with topical 8% capsaicin. Pain associated with the patch application could be successfully alleviated by pretreatment with topical lidocaine/prilocaine 2.5% and/or oral tramadol. Topical 8% capsaicin should be considered as a feasible treatment option for PHN. PMID- 26857303 TI - [Right-sided varicocele testis as the only sign of right-sided renal tumour]. AB - Testicular varicocele is an abnormal dilatation of the pampiniform venous plexus in scrotum. About 93% occur on the left side. Right-sided testicular varicocele is rare and can be caused by renal tumour, therefore ultrasound scan of the abdomen has been recommended to exclude the presence of occult malignancy. We report a case of renal cell carcinoma in a patient, who presented solely with right-sided testicular swelling caused by an underlying testicular varicocele. PMID- 26857304 TI - Spinal trauma. AB - The treatment of a patient with a vertebral fracture requires an accurate diagnosis and categorization of the problem. Treatment decisions must be based on clinical data and information about the lesion itself, which is provided by imaging studies and their interpretation. PMID- 26857305 TI - Paediatric diagnostic audiology testing in South Africa. AB - INTRODUCTION: With the increased emphasis on the importance of early identification of paediatric hearing loss within developing countries such as South Africa and Nigeria there has been a recognition of the ethical obligation to ensure access to timely diagnostic and intervention services for children identified with hearing loss; regardless of their geographic or socioeconomic status. There are limited studies on diagnosis of paediatric hearing loss in a developing world context. OBJECTIVES: The objective of this study was to determine processes used for diagnosis of paediatric hearing loss in South Africa, across the private and public healthcare sectors, and to profile the age of testing for each component of the diagnostic test battery. METHODS: Diagnostic audiology testing data of 230 children enrolled in an early intervention programme was analysed to profile the reporting of diagnostic audiology testing as well as diagnostic audiology procedures employed. Results were analysed according to province as well as healthcare sector to compare diagnostic services across regions as well as healthcare sectors. RESULTS: The differences in audiology practice and tests employed with paediatric clients across the regions of Gauteng, Kwazulu Natal and Western Cape indicates that services across regions and across the public and private sector are not equitable. Each region is equally unlikely to complete a full, comprehensive diagnostic evaluation on paediatric clients. The age of testing highlights the increased age of diagnosis of hearing loss. CONCLUSION: Paediatric diagnostic audiology is a section of Early Hearing Detection and Intervention services that requires attention in terms of the appropriateness of procedures as well as equity of services. Further studies on diagnostic practice and resources in South Africa will provide information on factors that are preventing adherence to international best practice guidelines for paediatric diagnostic audiology. PMID- 26857306 TI - Association between follicular tracheitis and gastroesophageal reflux. AB - OBJECTIVE: Follicular tracheitis (also known as tracheal cobblestoning) is an entity that is poorly described and of unclear significance. The objective of this study was to better define follicular tracheitis and determine the association between the clinical finding of follicular tracheitis on bronchoscopy and objective evidence of gastroesophageal reflux disease. METHODS: Retrospective chart review of children with recurrent croup having undergone a rigid bronchoscopy and an investigation for gastroesophageal reflux between 2001 and 2013. RESULTS: 117 children with recurrent croup children age 6-144 months were included in the study. Follicular tracheitis was noted on 41% of all bronchoscopies. Fifty-nine percent of all children who underwent bronchoscopy were diagnosed with gastroesophageal reflux on at least one investigation. Forty nine of 117 children underwent a pH probe study, and 51% were found to have evidence of reflux on this study. Nine children were diagnosed with eosinophilic esophagitis. Three patients underwent a biopsy of the follicular tracheitis lesions, which revealed chronic inflammation. There was no evidence of an association between findings of follicular tracheitis and a positive test for gastroesophageal reflux (p=0.52) or a positive pH probe study (p=0.64). There was no association between follicular tracheitis and subglottic stenosis (p=0.33) or an history of asthma and/or atopy (p=0.19). CONCLUSION: In children with recurrent croup, follicular tracheitis remains an unspecific finding associated with an inflammatory disorder of unknown etiology. PMID- 26857307 TI - Sleep problems and obstructive sleep apnea in children with down syndrome, an overwiew. AB - INTRODUCTION: Children with Down syndrome (DS) have a high prevalence of sleep problems, including behavioural sleep disturbances and obstructive sleep apnea. Sleep problems are associated with a wide range of adverse health effects. Since children with DS are already known to have many comorbidities, they are particularly susceptible for the negative impact of sleep problems. Aim of this study is (1) to evaluate the prevalence of sleep problems in children with DS, (2) compare the prevalence of sleep problems in children with DS with a community sample of typical developing school-aged children, and (3) to correlate the existence of sleep problems in children with DS and OSA. METHODS: Children enrolled at the multidisciplinary Down team of the University Hospital Antwerp and seen at the ENT department were eligible for this study. The prevalence of sleep problems was evaluated by the use of the Child Sleep Habits Questionnaire (CSHQ) and a full overnight polysomnography was performed to screen for obstructive sleep apnea. RESULTS: Parents of fifty-four children with DS, aged 7.5 years (5.4-11.6), completed the CSHQ and an overall prevalence of sleep problems was found in 74.1%. In 57.1% of the children OSA was diagnosed with a median obstructive apnea-hypopnea index (oAHI) 7.25/h (5.7-9.8). Overall sleep problems were not age-or gender related, however boys suffer more from daytime sleepiness. Symptoms of sleep disordered breathing correlate with parasomnias, a longer sleep duration and more daytime sleepiness. No correlation was found between sleep problems and underlying OSA. CONCLUSION: Children with Down syndrome have a significantly higher prevalence of sleep problems, compared to normal developing healthy school-aged children. We didn't find any correlation between the parental report of sleep problems and underlying OSA, or OSA severity. PMID- 26857308 TI - Hereditary angioedema type 2 presented as an orbital complication of acute rhinosinusitis. AB - Hereditary angioedema is an autosomal dominant and life-threatening disorder characterized by recurrent episodes of non-pitting edema affecting the skin, respiratory system and digestive tracts and caused by a congenital deficiency or function defect of the C1 esterase inhibitor. Preseptal cellulitis is defined as an infection of the tissues of the anterior orbital septum. It is generally caused by complications from an upper respiratory tract infection, dacryocystitis, dermal infection, and, rarely, sinusitis. The disease presents with orbital pain, edema on the eyelids, erythema, and fever. In this case, a child with hereditary angioedema type 2 who presented as mimicking a complication of acute sinusitis is discussed. PMID- 26857309 TI - Primary T-cell lymphoblastic lymphoma in the middle ear. AB - T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma characterized by precursor T-cell malignancy and lymphadenopathy or mediastinal involvement. We present the case of an 11-year-old boy with a diagnosis of middle ear T-LBL, which manifested as a headache, hearing loss and peripheral facial paralysis. The child was given intensive chemotherapy and had a complete response. To our knowledge, this is the first case reported in the literature of T-LBL originating in the middle ear. This case aims to help clinicians to be vigilant about the possibility of primary lesions at atypical sites in some special diseases. PMID- 26857310 TI - Long-term clinical outcomes of cochlear implantation in children with symptomatic epilepsy. AB - OBJECTIVES: To describe long-term clinical outcomes of cochlear implantation in deaf children with symptomatic epilepsy. MATERIALS AND METHODS: A retrospective data analysis review of patients implanted at the Cochlear Implant Center of the University of Parma, Italy, was performed, searching for implanted children with a confirmed diagnosis of symptomatic epilepsy. Clinical data, imaging findings, pre- and post-operative epilepsy pattern and EEG traces were analyzed; communicative skills were assessed using the Profile of Actual Linguistic Skills. RESULTS: Search retrieved two patients affected by profound bilateral sensorineural hearing loss and symptomatic epilepsy (associated respectively with methylmalonic acidemia and cerebral palsy). After careful parental counselling both patients were offered and underwent cochlear implantation. Activation and use of cochlear implant did not determine substantial changes of pre-existing seizure pattern and EEG traces. Both patients showed substantial development of their communicative abilities. CONCLUSIONS: Cochlear implantation in children with symptomatic epilepsy did not determine variations in seizure pattern or EEG traces. Both patients experienced substantial benefit from cochlear implantation. PMID- 26857311 TI - Electrically evoked compound action potential (ECAP) in cochlear implant children: Changes in auditory nerve response in first year of cochlear implant use. AB - AIM: Recording of the electrically evoked compound action potential (ECAP) of the auditory nerve in cochlear implant (CI) patients represents an option to assess changes in auditory nerve responses and the interaction between the electrode bundle and the neural tissue over time. The aim of the present work is to assess ECAP changes during the first year of cochlear implant for the purpose of predicting thresholds and adjustment of the patients' programs over time. METHOD: Data were collected from 25 children using Cochlear Nucleus 24 implants. ECAP thresholds were examined at the time of surgery, at initial stimulation, and 3, 6 and 12 months post-stimulation. Five electrodes located at basal, middle, and apical positions in the cochlea were tested at each time interval and ECAP thresholds were analyzed and compared. RESULTS: There was a significant decrease in ECAP thresholds between the intraoperative measure and fitting time at all electrode sites. Mean ECAP thresholds measured at 3, 6 and 12 months post stimulation remained similar to initial stimulation levels. Although there was no significant difference in ECAP thresholds recorded at fitting time and 12 months follow up session, there was significant increase in behavioral T and C levels from initial stimulation to the 12 months' time point. CONCLUSION: Most electrodes undergo non-significant change in ECAP thresholds over time, and therefore thresholds obtained on the day of initial stimulation can be used to estimate the patients' map levels at any time. On the other hand, intraoperative thresholds demonstrated significant change relative to postoperative recording times, limiting the ability to use intraoperatively recorded ECAP thresholds to predict postoperative measurements. PMID- 26857312 TI - Sudden sensorineural hearing loss in children: Etiology, management, and outcome. AB - BACKGROUND AND OBJECTIVES: Pediatric sudden sensorineural hearing loss (SSNHL) is uncommon, and the current guidelines for its management refer to adults. Our objective was to review cases of SSNHL in children and examine their etiologies, management, and outcome. METHODS: We performed a retrospective chart review of all children under the age of 18 years treated for SSNHL between January 2003 and September 2014. Data recorded included age, gender, symptoms, onset of hearing loss, audiometric results, diagnostic studies, treatment, and outcome. RESULTS: Nineteen children were included. Mean age was 14 years (range 7-18 years). Male: female ratio was 9:10. Degree of hearing loss varied from mild to profound across the tested frequencies. Most common accompanying symptom was tinnitus. Serologic tests demonstrated recent Epstein-Barr virus infection in one patient and previous cytomegalovirus infection in six patients. Imaging studies included computed tomography scan (n=3) and/or magnetic resonance imaging (n=12). All imaging studies did not demonstrate any pathology. Treatment included systemic steroids in 19 (100%) children and intratympanic steroids in eight (42%). Hearing completely improved in three (16%) children, partially improved in nine (47%), and there was no improvement in six (32%). One child was lost to follow-up. CONCLUSIONS: Viral infection was a common finding in children with SSNHL and no pathological changes were demonstrated on imaging studies. In most patients (63%), hearing improvement was observed. Intratympanic steroid injection can benefit these children. Further studies are required to investigate the etiologies and establish guidelines for the management of SSNHL in children. PMID- 26857313 TI - Swallowing dysfunction among patients with laryngeal cleft: More than just aspiration? AB - BACKGROUND: The Modified Barium Swallow (MBS) is the most widely utilized instrumental assessment of swallowing disorders in children; however, the exact role in the evaluation of laryngeal clefts remains controversial. METHODS: This study was an IRB-approved retrospective review on patients diagnosed with laryngeal cleft from 2002 to 2014. The objective was to describe the range of swallowing dysfunction that may be present in patients with laryngeal clefts both pre- and post-intervention (conservative management versus surgery). A speech language pathologist reviewed MBS studies and medical records to determine Penetration-Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS) scores. RESULTS: One hundred seventy-five patients who underwent laryngeal cleft repair during the study period (type 1, n=111; type 2, n=54; type 3, n=9; type 4, n=1) were included. Fifty patients who were managed conservatively (type 1) were also included. Swallowing impairment was demonstrated in all phases of swallowing for all cleft types. Oral phase impairment ranged from 27-67% pre-intervention to 19-75% post-intervention, triggering impairment from 24-42% pre-intervention to 24-75% post-intervention, and pharyngeal phase impairment (laryngeal penetration and aspiration) from 57-100% pre-intervention to 40-100% post-intervention. Laryngeal penetration and aspiration on thin and thick liquids, silent aspiration, PAS, and FOIS scores are reported. Significant improvements in swallowing function (p<0.05) were documented in all of the conservatively and surgically managed sub-groups. CONCLUSIONS: The MBS study is a useful tool for evaluating swallowing function in patients with laryngeal cleft and provides information beyond the lack or presence of aspiration. Understanding impairments in all phases of swallowing may be beneficial for perioperative management. PMID- 26857314 TI - Effect of local anesthesia on facial nerve blood flow and muscle action potential. AB - BACKGROUND & OBJECTIVE: The effect of direct application of local lidocaine with epinephrine on the facial nerve (FN) has not been reported. The aim of this study is to assess the effects of 2% lidocaine with 1:100,000 epinephrine at clinically relevant concentrations in a rat FN model with respect to facial nerve blood flow (FNBF) and subsequent electrophysiological changes. MATERIALS AND METHODS: To assess the influence of drugs on FNBF and electrically evoked muscle action potential (EMAP), small pieces of gelfoam were soaked in PBS 100MUl (n=5, control group), 50MUl (n=5, treatment group A) and 100MUl (n=5, group B) of 2% lidocaine with 1:100,000 epinephrine, and 50MUl (n=5, group C) and 100MUl (n=5, group D) of 2% lidocaine. After 5min of stable recordings, we applied a 2% lidocaine with or without 1:100,000 epinephrine impregnated gelfoam over the main trunk of the facial nerve of rats for 30min. After removing the applied gelfoam, FNBF and threshold of EMAP were measured separately in each group. RESULTS: Compared to the control group, the treatment groups showed a significant reduction in FNBF in a dose-dependent manner. The maximal reductions in FNBF were observed in all treatment groups for a period after 10min of the application. Synergistic reduction in FNBF was greater in groups A and B than in the lidocaine applied groups (C and D). The maximal increase in the EMAP threshold was observed immediately after the respective drug application in all groups. The greatest increase in the EMAP threshold was observed in group B. The increased EMAP threshold returned to the baseline value within 120min in groups A and C. CONCLUSION: From these results, it can be considered that the topical application of lidocaine with epinephrine caused reduction in FNBF and elevation of EMAP threshold. These acute reductions in FNBF and elevations in the EMAP threshold were restored in a time-dependent manner. PMID- 26857315 TI - Deeper insertion of electrode array result in better rehabilitation outcomes - Do we have evidence? AB - OBJECTIVE: To study the outcome analysis in cochlear implantees in relation to depth of insertion. METHODS: 30 patients of non-syndromic congenital profound hearing loss in the age range of 2-12 years received cochlear implantation by a posterior tympanotomy round window approach. Depth of insertion was calculated using post-operative X-rays (modified Stenver's view) and categorized into four groups, viz. fair insertion (Group A <180 degrees ), good insertion (Group B 180 <270 degrees ), very good insertion(Group C 270-360 degrees ), excellent insertion (Group D >360 degrees ). The outcome analysis of each implantee was carried out in a follow up interval of every 3 months using Meaningful Auditory Integration Scale (MAIS), Infant Toddler Meaningful Auditory Integration Scale (IT-MAIS), Category of Auditory Performance (CAP), and Speech Intelligibility Rating (SIR). RESULTS: Overall 30, 29, 25, and 22 patients have completed 3, 6, 9, and 12 months follow up respectively. The MAIS scores in Group C were significantly better than Group B at 6, 9, and 12 months (P<0.05). The mean CAP score of Group C was more than rest of the groups with significant difference between Group C and Group D at 12 months (P<0.05). The mean SIR scores were maximum in Group C with significant difference between Group C and Group B at 9 and 12 months (P<0.05). CONCLUSION: The study demonstrates that insertion from 270 degrees to 360 degrees gives optimum hearing outcomes as compared to deeper insertion, although larger sample and long term follow-up is warranted for definite conclusions. PMID- 26857316 TI - Clinical outcomes in a high nursing ratio ward setting for children with obstructive sleep apnea at high risk after adenotonsillectomy. AB - BACKGROUND: In 2012 clinical management of children having adenotonsillectomy (AT) for suspected obstructive sleep apnea (OSA) at our tertiary centre changed based on previous research: children with severe obstructive sleep apnea (OSA) at increased risk of post-operative respiratory adverse events (AE) identified using home overnight oximetry or polysomnography (PSG) were managed post-operatively in a high nurse/patient ratio unit in the ward (high acuity unit, HAU) rather than in the intensive care unit (ICU) as previously. OBJECTIVES: To examine the post operative respiratory AE post AT in HAU. METHODS: A retrospective audit was performed of children having AT on the HAU list from Oct 2012-Sept 2014, identifying clinical information, pre-operative testing for OSA and post operative course. RESULTS: 343 children underwent elective adenotonsillectomy at our tertiary centre in the study period, of whom 79 had surgery on the HAU list (16F; median age 4.2year (range 1.2-14.7); median weight-for-age centile 77.9% (IQR 44-98.7%)). 75 had moderate/severe OSA by oximetry (n=44) or PSG (n=31) criteria. 77 of 79 children had oxygen therapy in the recovery room (median 20min, IQR 15-40min). 18 (23%) had at least one AE outside the recovery room, which were observed (n=2) or treated with oxygen therapy (n=14) or repositioning (n=2). Obesity increased the risk of an AE (10/25 obese vs 8/54 non obese, p=0.01), as did the presence of a major comorbidity (5/9 with comorbidity vs 13/70 without, p=0.03). There were no admissions from the HAU to ICU. 63 patients (83%) stayed only one night in hospital (median 1d, range 1-5d). CONCLUSIONS: In a cohort of children with known moderate-severe OSA, post-operative AE after AT were all managed in the HAU. Post-operative care in HAU provides safe and effective care for high-risk children post-AT, minimizing admissions to ICU. PMID- 26857317 TI - Prelingual auditory-perceptual skills as indicators of initial oral language development in deaf children with cochlear implants. AB - OBJECTIVES: To assess when prelingually deaf children with a cochlear implant (CI) achieve the First Milestone of Oral Language, to study the progression of their prelingual auditory skills in the first year after CI and to investigate a possible correlation between such skills and the timing of initial oral language development. METHODS: The sample included 44 prelingually deaf children (23 M and 21 F) from the same tertiary care institution, who received unilateral or bilateral cochlear implants. Achievement of the First Milestone of Oral Language (FMOL) was defined as speech comprehension of at least 50 words and speech production of a minimum of 10 words, as established by administration of a validated Italian test for the assessment of initial language competence in infants. Prelingual auditory-perceptual skills were assessed over time by means of a test battery consisting of: the Infant Toddler Meaningful Integration Scale (IT-MAIS); the Infant Listening Progress Profile (ILiP) and the Categories of Auditory Performance (CAP). RESULTS: On average, the 44 children received their CI at 24+/-9 months and experienced FMOL after 8+/-4 months of continuous CI use. The IT-MAIS, ILiP and CAP scores increased significantly over time, the greatest improvement occurring between baseline and six months of CI use. On multivariate regression analysis, age at diagnosis and age at CI did not appear to bear correlation with FMOL timing; instead, the only variables contributing to its variance were IT-MAIS and ILiP scores after six months of CI use, accounting for 43% and 55%, respectively. CONCLUSION: Prelingual auditory skills of implanted children assessed via a test battery six months after CI treatment, can act as indicators of the timing of initial oral language development. Accordingly, the period from CI switch-on to six months can be considered as a window of opportunity for appropriate intervention in children failing to show the expected progression of their auditory skills and who would have higher risk of delayed oral language development. PMID- 26857318 TI - Effects of ear canal static pressure on the dynamic behaviour of outer and middle ear in newborns. AB - OBJECTIVE: The present study investigated the effect of ear canal pressure on the dynamic behaviour of the outer and middle ear in newborns with and without a conductive condition using the sweep frequency impedance (SFI) technology. METHODS: A test battery consisting of automated auditory brainstem response (AABR), transient evoked otoacoustic emission (TEOAE) and 1000-Hz tympanometry (HFT) was performed on 122 ears of 86 healthy newborns and 10 ears of 10 newborns with a conductive condition (failed TEOAE and HFT). The dynamic behaviour of the outer and middle ear, when the pressure applied to the ear canal was varied from 200 to -200daPa, was evaluated in terms of the sound pressure level (SPL) in the ear canal, resonance frequency (RF) and displacement (DeltaSPL). RESULTS: Application of either a positive or negative static pressure to the ear canal of healthy newborns increased the resonance frequency of the outer (RF1) and middle ear (RF2), but decreased the displacements of the outer (DeltaSPL1) and middle ear (DeltaSPL2). Positive static pressures resulted in lower SPL while negative static pressures resulted in higher SPL than that at ambient pressure (0daPa). At -200daPa, more than 90% of ears showed signs of collapsed ear canal. The dynamic behaviour under various positive and negative static pressures for newborn ears with a conductive condition indicated similar pattern of SPL, RF1 and DeltaSPL1 responses for the outer ear as per healthy ears, but abnormal responses for the middle ear. CONCLUSIONS: While both positive and negative pressures applied to the ear canal have the same effect of stiffening the outer and middle ear, negative pressure of up to -200daPa resulted in more than 90% of ears with a collapsed ear canal. The results of the present study do not only offer useful clinical information for differentiating healthy ears from ears with a conductive condition, but also provide information on the maturation aspects of the outer and middle ear in newborns. PMID- 26857319 TI - Analysis of histopathological aspects and bone destruction characteristics in acquired middle ear cholesteatoma of pediatric and adult patients. AB - OBJECTIVE: The aim of this study was to investigate the proliferative and apoptotic activity of middle ear cholesteatoma in pediatric and adult patients, in addition to comparing its histopathological aspects and the severity of advanced bone destruction. MATERIALS AND METHODS: Medical records of 223 patients treated for chronic otitis media with cholesteatoma at the Otolaryngology Department of Dokuz Eylul University between January 1992 and December 2013 were retrospectively evaluated. Sixty-one patients subjected to tympanomastoidectomy due to middle ear cholesteatoma, with sufficient specimens for histopathological examination, were included in the study. Sections of archived tissues in paraffin blocks were subjected to new histopathological examinations. The proliferative and apoptotic activities of cholesteatoma were determined by immunohistochemical staining for epithelial thickness (ET), and Ki-67 and caspase-3 expression. A novel scoring system, the Bone Erosion Score (BES), was developed to estimate the severity of bone destruction. The Austin-Kartush classification score (AKCS) was also calculated. RESULTS: ET and Ki-67 expression was higher in adult patients than in the pediatric patients (p=0.009 and 0.01, respectively); however, caspase 3 immunopositivity did not show any significant intergroup differences (p=0.106). The differences in AKCS and BES between pediatric and adult patients were not statistically significant. According to the correlation analysis, a significant positive correlation was observed between AKCS and BES (p=0.001), and between ET and Ki-67 expression (when histopathological data were compared) (p=0.001). CONCLUSION: The proliferative activity of cholesteatoma was higher in adult patients. Therefore, these findings do not support the theory that the aggressive clinical course of cholesteatoma in pediatric patients is correlated with its histopathological characteristics. PMID- 26857320 TI - The role of larygotracheal reconstruction in the management of recurrent croup in patients with subglottic stenosis. AB - OBJECTIVES: To determine the role of laryngotracheal reconstruction for recurrent croup and evaluate surgical outcomes in this cohort of patients. METHODS: Retrospective chart review at a tertiary care pediatric hospital. RESULTS: Six patients who underwent laryngotracheal reconstruction (LTR) for recurrent croup with underlying subglottic stenosis were identified through a search of our IRB approved airway database. At the time of diagnostic bronchoscopy, all 6 patients had grade 2 subglottic stenosis. All patients were treated for reflux and underwent esophageal biopsies at the time of diagnostic bronchoscopy; 1 patient had eosinophilic esophagitis which was treated. All patients had a history of at least 3 episodes of croup in a 1 year period requiring multiple hospital admissions. Average age at the time of LTR was 39 months (range 13-69); 5 patients underwent anterior graft only and 1 patient underwent anterior and posterior grafts. Patients were intubated for an average of 5 (range 3-8) days and hospitalized for an average of 12 (range 7-20) days post-operatively. One patient experienced narcotic withdrawal post-operatively, but there were no other post-operative complications. All patients underwent follow-up airway endoscopy within 4 weeks and none required any further dilation procedures. Average post operative follow-up was 24 months (range 10-48) and none of the patients experienced any further episodes of croup. CONCLUSIONS: Single stage LTR is a safe and effective treatment for recurrent croup in the setting of underlying subglottic stenosis, and should be considered in patients who are refractory to medical management. PMID- 26857321 TI - Cervical lymphadenopathies in children: A prospective clinical cohort study. AB - AIM: Cervical lymphadenopathy (LAP) is a common sign and may raise fears about serious illnesses. The aim of our study was to evaluate the patients with cervical LAPs in a general pediatrics clinic setting, and to evaluate follow-up results for potential causes and risk factors for malignancies. MATERIAL AND METHODS: Two hundred-eighteen patients aged between 79.4+/-46.7 months with LAP were enrolled in this prospective cohort study. The patients were examined in terms of demographics, clinical, radiologic and serologic aspects like Epstein Barr virus (EBV), cytomegalovirus (CMV), parvovirus B19. A lymph node biopsy was performed in selected patients. The patients were followed-up for 8 weeks and risk factors for malignancy were evaluated. RESULTS: Seventy patients (41.3%) had specific etiology and 6 (2.7%) had malignant causes. The causes were as follows: 27% (n=59) infections; 2.7% (n=6) malignancies; 11.4% (n=25) other causes. EBV was responsible for 27% of infectious causes. The other common infectious etiologies were CMV 4.3%, parvovirus B-19 2.9%, and group-A beta-hemolytic streptococcus (GAS) 10.8%. Four of the six malignancies were lymphomas. Predictive factors for malignancy were having LAP larger than 30mm, rubbery lymph node, high serum CRP and LDH values, no hilum in ultrasonography, and enlargement of lymph node in follow-up. High uric acid levels and leucopenia were also common in the malignancy group. CONCLUSION: Etiology of cervical LAPs was diagnosed in 41.3% patients. Infectious causes were the most common cause with 27%. Malignancy was diagnosed in 2.7% and lymphoma was the most common malignancy. PMID- 26857322 TI - The efficacy and safety of airway foreign body removal by balloon catheter via flexible bronchoscope in children - A retrospective analysis. AB - OBJECTIVES: To investigate the efficacy and safety of the airway foreign body removal by balloon catheter via flexible bronchoscope in children. METHODS: Retrospective analysis was performed of 26 cases of airway foreign body removal in children by balloon catheter via flexible bronchoscope in the First Affiliated Hospital of Guangzhou Medical University between December 2006 and December 2014. RESULTS: There were 14 males and 12 females, aging between 1 and 12 years (median age: 25 months). The clinical course ranged from 0.5h to 60 days (median: 3 days). The foreign bodies consisted of peanuts (16 cases), soybeans (3 cases), pumpkin seeds (3 cases), porcine bone (1 case), olive nut (1 case), and a plant based object (1 case). All foreign bodies were successfully removed. The operation duration ranged from 3 to 15 (5.3+/-2.9)min. No complication was observed such as hemorrhage, pneumothorax, or airway laceration. CONCLUSIONS: Balloon catheter via flexible bronchoscope is a safe, effective, and easily performed method of removing airway non-sharp foreign bodies in children. PMID- 26857323 TI - Universal newborn hearing screening in Umbria region, Italy. AB - OBJECTIVE: In Italy, universal newborn hearing screening (UNHS) was first introduced in some regions from 1997. Umbria Region has launched a UNHS program in all hospitals, which has been implemented throughout the region since July 2010. Before UNHS implementation in Umbria region, the average age of identification of congenital hearing loss was around 32 months of age with an average age of initial amplification treatment at least 2 months later. The coverage rate of newborn screening was only 34.4% in 2006. The aim of this study was to examine the results of this program and its evolution in the first 2.5 years since implementation in our region. METHODS: Since July 2010, all 11 birth centers and hospitals in Umbria region have been involved in a UNHS program. The screening involves the automated otoacoustic emissions (AOAE) test and automatic auditory brain stem response (AABR) audiometry. The number of screening stages and tests used were different depending on whether the infants had audiological risk factors or not. RESULTS: A total of 20,841 babies were born in the hospitals involved of whom 20,051 were well born babies (WB), while 790 babies (3.8%) presented identified audiological risk factors (BRF). The overall coverage rate in the study period was 93.8%. The prevalence of hearing loss was 20/00 for WB infants and 4.3% for BRF. Mean age at diagnosis was 5.31+/-3.95 and 11.28+/-7.73 months in the WB and BRF groups, respectively. CONCLUSIONS: UNHS has allowed us to substantially increase the coverage rates and decrease the mean age at diagnosis and subsequent treatment. The identification of audiological risk factors is very important for adequate screening and follow-up. However the Joint Committee on Infant Hearing 2007 quality indicators and benchmarks for screening have not yet been fully achieved and there is still scope for some improvement. This could be achieved with a closer cooperation among institutions, parents, pediatricians, and ENT doctors. PMID- 26857324 TI - Carotid artery dissection following adenoidectomy. AB - Carotid dissection and cerebral infarction are extremely rare complications of adenoidectomy. We describe the case of seven year old girl, who suffered from left internal carotid artery dissection following adenoidectomy, leading to right hemiplegia with global aphasia. A CT angiogram confirmed a loop in contralateral right internal carotid artery. It is presumed that a similar loop also existed in left internal carotid artery, which possibly extended medially close to posterior pharyngeal wall and was injured during the course of surgery. PMID- 26857325 TI - Non-tuberculous mycobacterial head and neck infections in children: Analysis of results and complications for various treatment modalities. AB - OBJECTIVES: Analyze the results and complications of various surgical interventions in a large cohort of children with non-tuberculous mycobacterial (NTM) head and neck infections and suggest a heuristic treatment protocol for managing this condition while aiming to maximize cure and minimize complications. METHODS: Retrospective chart review of 104 consecutive patients diagnosed with head and neck NTM at a tertiary paediatric hospital between January 1994 and December 2013 inclusive. RESULTS: 104 patients ranged in age between 8 months to 15 years (mean age 27 months) were reviewed and 97 patients were included in the final analysis. 6 patients excluded due to lack of follow-up and one excluded due to systemic immunocompromised condition. Sub-sites of NTM infections were submandibular (n=48, 46%), cervical (n=40, 38%), parotid (n=18, 17%) and submental (n=4, 4%). Some patients had more than one lesion so counted twice. Higher cure rates were demonstrated for primary excision (81%, p<0.01) versus incisional interventions (44%, p<0.01). Marginal mandibular nerve palsy following surgery was seen in 7 patients (7.2%). This was permanent in 4 patients (4%) and temporary in 3 patients (3%). All children who were complicated with marginal mandibular palsies had lesions in the submandibular region. The rate of palsy for submandibular disease alone was 15%, while 8% presented permanent palsy and 6% temporary. Marginal mandibular nerve palsy was more likely following excisional compared to incisional procedures (6 versus 1 patient, p<0.01). Hypertrophic scarring occurred in 7 patients: 3 patients following excision and 4 patients after an incisional procedure. One patient suffered long term spinal accessory nerve damage presented as winged scapula. CONCLUSIONS: Excision of NTM provides better cure rates compared to incision although at the expense of long term post surgical morbidity. Excision should probably be the first line of treatment when the risk for neural damage is low. Incision and drainage with or without antimycobacterial treatment may be the preferred option for at-risk sub-sites (submandibular or parotid) in order to reduce long term morbidity. PMID- 26857326 TI - Packing and Problematic Feeding Behaviors in CHARGE Syndrome: A Qualitative Analysis. AB - OBJECTIVE: To understand packing and problematic feeding behaviors during mealtime in individuals with CHARGE syndrome. Packing, or holding food in one's cheeks without swallowing, is an adverse feeding behavior that has been described in children with autism and Down syndrome, and in those transitioning from tube to oral feeding. It has never been described in detail in CHARGE syndrome, a genetic disorder with a high prevalence of feeding difficulties, tube feeding, and otorhinolaryngological issues. METHODS: A mixed methods approach used descriptive and qualitative content analysis of interviews with parents of children, adolescents, and adults with CHARGE syndrome. Individuals had previously or were currently experiencing packing or overstuffing one's mouth with food during eating. RESULTS: Twenty parents completed a phone interview, describing their child/adult's (2-32 years) adverse feeding behaviors. Individuals had a higher proportion of cleft palates (40%) in comparison to the general CHARGE population (15-20%). Parents reported food packing most commonly with bread and pasta (33%), and reported that food was held in cheeks for hours after a meal had ended (35%). Packing was reported to prolong mealtimes for over an hour (30%). Parents were worried about choking during eating (30%). Food packing was also reported in individuals who had never needed G/J tube feeding or feeding therapy, in addition to those who had needed both. CONCLUSION: This study provides an in-depth description of parents' experiences with packing and adverse feeding behaviors in individuals with CHARGE syndrome. These feeding behaviors are an important addition to the knowledge of the highly prevalent feeding difficulties in this genetic disorder. Individualized evaluation of feeding behavior should be a part of the standard otolaryngologic and feeding team practice for these patients. PMID- 26857327 TI - Safety of paediatric day-stay laryngeal surgery for recurrent respiratory papillomatosis. AB - OBJECTIVES: Safety assessment of day-stay laryngeal surgery in a cohort of children with recurrent respiratory papillomatosis (RRP). Recurrent respiratory papillomatosis is a chronic debilitating disease which usually requires multiple recurrent interventions under general anaesthesia. Day-stay surgery is an attractive option as it allows avoiding the inconvenience and costs of routine overnight admissions while recovering in the safe environment of the family home. This is the first study to assess the safety of day-stay laryngeal surgery in this cohort of patients. METHODS: Retrospective cohort study of all consecutive RRP procedures performed between December 1998 and May 2015 in a single paediatric tertiary-level hospital. RESULTS: A total of 465 surgical procedures were performed in 20 patients. Average age on diagnosis was 4.5 years. 415 (89.25%) of the procedures were done as day cases without overnight admission. Average number of procedures per patient was 20 and 25 for Children positive to HPV6 and HPV11, respectively. Only one patient after one single procedure (presenting 0.21% of total procedures, 0.24% of day-stay procedures) represented after discharge. CONCLUSIONS: Day-stay surgery for children with RRP has a favourable safety profile in selected cases. PMID- 26857328 TI - The German Validation Study of the Surgical Intensive Care Unit Optimal Mobility Score. AB - PURPOSE: Immobilization of critically ill patients leads to muscle weakness, which translates to increased costs of care and long-term functional disability. We tested the validity of a German Surgical Intensive Care Unit (ICU) Optimal Mobilization Score (SOMS) in 2 different cohorts (neurocritical and nonneurocritical care patients). MATERIALS AND METHODS: Physical therapists estimated the patients' mobilization capacity by using the German version of the SOMS the morning after admission. We tested the prognostic value of the prediction for ICU and hospital length of stay (LOS) as well as for mortality, and built a model to account for other known predictors of these outcomes in the 2 cohorts. RESULTS: A total of 128 patients were included in the analysis, 48 of these were neurocritical care patients. The SOMS predicted mortality and ICU and hospital LOS. Neurocritical care patients stayed significantly longer in the ICU (median 12 vs 4 days, P < .001) and in the hospital (25 vs 17 days, P = .02). The SOMS predicted ICU and hospital LOS. It predicted mortality only in nonneurocritical patients. CONCLUSIONS: The German SOMS assessed by physical therapists on the day after ICU admission predicts ICU and hospital LOS, and mortality. Our data suggest that the association between early mobilization and mortality is more complex in neurocritical care patients. PMID- 26857329 TI - Using the brain criterion in organ donation after the circulatory determination of death. AB - The UK, France, and Switzerland determine death using the brain criterion even in organ donation after the circulatory determination of death (DCDD), in which the United States and Canada use the circulatory-respiratory criterion. In our analysis of the scientific validity of the brain criterion in DCDD, we concluded that although it may be attractive in theory because it conceptualizes death as a unitary phenomenon, its use in practice is invalid. The preconditions (ie, the absence of reversible causes, such as toxic or metabolic disorders) for determining brain death cannot be met in DCDD. Thus, although brain death tests prove the cessation of tested brain functions, they do not prove that their cessation is irreversible. A stand-off period of 5 to 10 minutes is insufficient to achieve the irreversibility requirement of brain death. Because circulatory cessation inevitably leads to cessation of brain functions, first permanently and then irreversibly, the use of brain criterion is unnecessary to determine death in DCDD. Expanding brain death to permit it to be satisfied by permanent cessation of brain functions is controversial but has been considered as a possible means to declare death in uncontrolled DCDD. PMID- 26857330 TI - Severe electrical exit burn to the hand associated with single shock from a defibrillator device. PMID- 26857331 TI - [Bi-thalamic abnormality]. PMID- 26857332 TI - Identification of 14-3-3zeta associated protein networks in oral cancer. AB - Advancements in genomics, proteomics, and bioinformatics have improved our understanding of gene/protein networks involved in intra- and intercellular communication and tumor-host interactions. Using proteomics integrated with bioinformatics, previously we reported overexpression of 14-3-3zeta in premalignant oral lesions and oral squamous cell carcinoma tissues in comparison with normal oral epithelium. 14-3-3zeta emerged as a novel molecular target for therapeutics and a potential prognostic marker in oral squamous cell carcinoma patients. However, the role of 14-3-3zeta in development and progression of oral cancer is not known yet. This study aimed to identify the 14-3-3zeta associated protein networks in oral cancer cell lines using IP-MS/MS and bioinformatics. A total of 287 binding partners of 14-3-3zeta were identified in metastatic (MDA1986) and nonmetastatic (SCC4) oral cancer cell lines including other 14-3-3 isoforms (2%), proteins involved in apoptosis (2%), cytoskeleton (9%), metabolism (16%), and maintenance of redox potential (2%). Our bioinformatics analysis revealed involvement of 14-3-3zeta in protein networks regulating cell cycle, proliferation, apoptosis, cellular trafficking, and endocytosis in oral cancer. In conclusion, our data revealed several novel protein interaction networks involving 14-3-3zeta in oral cancer progression and metastasis. PMID- 26857333 TI - The complexity of diagnosing postural orthostatic tachycardia syndrome: influence of the diurnal variability. AB - We investigated how the diagnosis of postural orthostatic tachycardia syndrome (POTS) would be changed due to diurnal variability in orthostatic tachycardia. The orthostatic vital sign test was administered to each patient twice, in the afternoon of the day of admission and the next morning (n = 113). Forty-six patients were diagnosed with POTS, and the remaining 67 patients were assigned to non-POTS group. Heart rate increments after standing were larger in the morning than in the afternoon in every group (all P < .001). Among the POTS patients, 82.6% fulfilled the diagnostic criteria for POTS in the morning and 52.2% in the afternoon. Most POTS group (65.2%) displayed normal result on single orthostatic vital sign test. Orthostatic intolerance symptoms were provoked in only 45.7% of the POTS patients, more frequently in the morning. In conclusion, diurnal variability in hemodynamic parameters and provoked symptoms significantly challenged the diagnosis of POTS. PMID- 26857334 TI - Regions involved in fengycin synthetases enzyme complex formation. AB - BACKGROUND: Fengycin is a lipopeptide antibiotic synthesized nonribosomally by five fengycin synthetases. These enzymes are linked in a specific order to form the complex. This study investigates how these enzymes interact in the complex and analyzes the regions in the enzymes that are critical to the interactions. METHODS: Deletions were generated in the fengycin synthetases. The interaction of these mutant proteins with their partner enzymes in the complex was analyzed in vitro by a glutathione S-transferase (GST) or nickel pulldown assay. RESULTS: The communication-mediating donor (COM-D) domains of the fengycin synthetases, when fused to GST, specifically pulled down their downstream partner enzymes in the GST-pulldown assays. The communication-mediating acceptor (COM-A) domains were required for binding between two partner enzymes, although the domains alone did not confer specificity of the binding to their upstream partner enzymes. This study found that the COM-A domain, the condensation domain, and a portion of the adenylation domain in fengycin synthetase B (FenB) were required for specific binding to fengycin synthetase A (FenA). CONCLUSION: The interaction between the COM-D and COM-A domains in two partner enzymes is critical for nonribosomal peptide synthesis. The COM-A domain alone is insufficient for interacting with its upstream partner enzyme in the enzyme complex with specificity; a region that contains COM-A, condensation, and a portion of adenylation domains in the downstream partner enzyme is required. PMID- 26857335 TI - Treatment response to unboosted atazanavir in combination with tenofovir disoproxil fumarate and lamivudine in human immunodeficiency virus-1-infected patients who have achieved virological suppression: A therapeutic drug monitoring and pharmacogenetic study. AB - BACKGROUND/PURPOSE: Treatment response to switch regimens containing unboosted atazanavir and tenofovir disoproxil fumarate (TDF)/lamivudine guided by therapeutic drug monitoring in human immunodeficiency virus-infected patients is rarely investigated. METHODS: Consecutive patients with plasma human immunodeficiency virus RNA load < 200 copies/mL switching to unboosted atazanavir plus zidovudine-lamivudine (coformulated), abacavir-lamivudine (coformulated), or TDF/lamivudine > 3 months were included for determinations of treatment response, plasma atazanavir concentrations, and single-nucleotide polymorphisms of MDR1, PXR, and UGT1A1 genes from 2010 to 2014. Treatment failure was defined as either discontinuation of atazanavir for any reason or plasma viral load >= 200 copies/mL within 96 weeks. RESULTS: During the study period, 128 patients switched to unboosted atazanavir with TDF/lamivudine (TDF group) and 186 patients switched to unboosted atazanavir with two other nucleoside reverse-transcriptase inhibitors (non-TDF group). There were no statistically significant differences in the distributions of single-nucleotide polymorphisms of MDR1 (2677 and 3435), PXR genotypes (63396), and UGT1A1*28 between the two groups. Recommended plasma atazanavir concentrations were achieved in 83.5% and 64.9% of the TDF group and non-TDF group, respectively (p < 0.01). After a median follow-up duration of 96.0 weeks, treatment failure occurred in 19 (14.9%) and 34 (18.3%) patients in the TDF group and non-TDF group, respectively (p = 0.60). Low-level viremia (40-200 copies/mL) before switch (adjusted hazard ratio, 2.12; 95% confidence interval, 1.12-4.01) and without therapeutic drug monitoring (adjusted hazard ratio, 2.08; 95% confidence interval, 1.16-3.73) were risk factors for treatment failure. CONCLUSION: Switch to unboosted atazanavir with TDF/lamivudine achieves a similar treatment response to that with two other nucleoside reverse-transcriptase inhibitors in patients achieving virological suppression with the guidance of therapeutic drug monitoring. PMID- 26857336 TI - Analgesic and Sensory Effects of the Pecs Local Anesthetic Block in Patients with Persistent Pain after Breast Cancer Surgery: A Pilot Study. AB - BACKGROUND: Persistent pain after breast cancer surgery (PPBCS) develops in 15% to 25% of patients, sometimes years after surgery. Approximately 50% of PPBCS patients have neuropathic pain in the breast, which may be due to dysfunction of the pectoral nerves. The Pecs local anesthetic block proposes to block these nerves and has provided pain relief for patients undergoing breast cancer surgery, but has yet to be evaluated in patients with PPBCS. METHODS: The aim of this pilot study was to examine the effects of the Pecs block on summed pain intensity (SPI) and sensory function (through quantitative sensory testing [QST]) in eight patients with PPBCS. SPI and QST measurements were recorded before and 30 minutes after administration of the Pecs block (20 mL 0.25% bupivacaine). Pain intensity and sleep interference were measured daily before and after the block for 7 days. RESULTS: Patients experienced analgesia (P = 0.008) and reduced hypoesthesia areas to cold (P = 0.004) and warmth (P = 0.01) after 30 minutes. The reported pain relief (P = 0.02) and reduced sleep interference (P = 0.01) persisted for 7 days after the block. CONCLUSIONS: This pilot study suggests that the pectoral nerves play a role in the maintenance of pain in the breast area in PPBCS and begs for further research. PMID- 26857337 TI - A novel engineered dermis for in vitro photodamage research. AB - The realization of biologically relevant human tissue equivalents as an in vitro model to investigate human diseases, as well as to test the efficacy or toxicity of novel compounds, is emerging as a new challenge in tissue engineering. Currently, the in vitro three-dimensional (3D) dermis model mainly involves the use of cells embedded in exogenous non-human matrices. However, such models feature biological and functional disparities with native dermis, therefore limiting their relevance to the in vivo situation. The purpose of this study was to provide a reliable endogenous human dermal equivalent (HDE) able to recapitulate the extracellular matrix (ECM) remodelling of the native dermis occurring after external damage. To this end, UVA irradiation was used to induce photodamage to both the HDE and to a fibroblast-populated collagen matrix. The photodamage was investigated at the cellular and ECM level and the results showed that, although a cellular response was detected in both systems, no ECM reorganization characteristic of the in vivo photo-aged dermis could be detected in the fibroblast-populated collagen matrix. In contrast in the HDE, the neosynthesized ECM recapitulated the characteristic ageing behaviour of the dermis found in vivo, in terms of collagen and hyaluronic acid synthesis as well as collagen organization remodelling. This study therefore demonstrates the role of the endogenous ECM in recapitulating in vitro the functionality of the human dermis and the proposed HDE as a novel tool for photoprotection trials. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26857338 TI - Removal of ionizable aromatic pollutants from contaminated water using nano gamma Fe2O3 based magnetic cationic hydrogel: Sorptive performance, magnetic separation and reusability. AB - Acid dyes found in textile industrial effluents are hazardous aromatic pollutants which ionize in aqueous environments. Owing to their non-biodegradability, conventional wastewater treatment processes are not able to remove them and sorptive treatment systems can alternatively be employed. In this study, a nano gamma-Fe2O3 based magnetic cationic hydrogel, synthesized through a facile method, was applied for the removal of two acid dyes (Acid Red 27 and Acid Orange 52). The sorption performance (e.g., capacity and kinetics) and solution matrix effects (e.g., pH and competing anions) were investigated. Furthermore, different regeneration conditions (e.g., composition, strength and amount) were tested to develop a suitable regeneration strategy, based on which, reusability of the material was investigated for 30 consecutive sorption-desorption cycles. The material exhibited a rapid sorption rate (99% dye removal within 5min) and sorption isotherm data agreed well with the Langmuir model with an estimated maximum capacity of 833mg/g and 1430mg/g for Acid Red 27 and Acid Orange 52, respectively. The high sorptive performance persisted not only over a wide pH range but also over 30 consecutive rounds of sorption-desorption. Moreover, the impregnated gamma-Fe2O3 nanoparticles rendered the hydrogel superparamagnetic allowing its convenient magnetic separation. PMID- 26857340 TI - Role of neutrophil to lymphocyte ratio in the prognosis of male patients with hepatocellular carcinoma undergoing liver transplantation. PMID- 26857339 TI - Research Synthesis Methods in an Age of Globalized Risks: Lessons from the Global Burden of Foodborne Disease Expert Elicitation. AB - We live in an age that increasingly calls for national or regional management of global risks. This article discusses the contributions that expert elicitation can bring to efforts to manage global risks and identifies challenges faced in conducting expert elicitation at this scale. In doing so it draws on lessons learned from conducting an expert elicitation as part of the World Health Organizations (WHO) initiative to estimate the global burden of foodborne disease; a study commissioned by the Foodborne Disease Epidemiology Reference Group (FERG). Expert elicitation is designed to fill gaps in data and research using structured, transparent methods. Such gaps are a significant challenge for global risk modeling. Experience with the WHO FERG expert elicitation shows that it is feasible to conduct an expert elicitation at a global scale, but that challenges do arise, including: defining an informative, yet feasible geographical structure for the elicitation; defining what constitutes expertise in a global setting; structuring international, multidisciplinary expert panels; and managing demands on experts' time in the elicitation. This article was written as part of a workshop, "Methods for Research Synthesis: A Cross Disciplinary Approach" held at the Harvard Center for Risk Analysis on October 13, 2013. PMID- 26857341 TI - Protein kinase C-dependent regulation of ClC-1 channels in active human muscle and its effect on fast and slow gating. AB - KEY POINTS: Regulation of ion channel function during repeated firing of action potentials is commonly observed in excitable cells. Recently it was shown that muscle activity is associated with rapid, protein kinase C (PKC)-dependent ClC-1 Cl(-) channel inhibition in rodent muscle. While this PKC-dependent ClC-1 inhibition during muscle activity was shown to be important for the maintenance of contractile endurance in rat muscle it is unknown whether a similar regulation exists in human muscle. Also, the molecular mechanisms underlying the observed PKC-dependent ClC-1 inhibition are unclear. Here we present the first demonstration of ClC-1 inhibition in active human muscle fibres, and we determine the changes in ClC-1 gating that underlie the PKC-dependent ClC-1 inhibition in active muscle using human ClC-1 expressed in Xenopus oocytes. This activity induced ClC-1 inhibition is suggested to represent a mechanism by which human muscle fibres maintain their excitability during sustained activity. ABSTRACT: Repeated firing of action potentials (APs) is known to trigger rapid, protein kinase C (PKC)-dependent inhibition of ClC-1 Cl(-) ion channels in rodent muscle and this inhibition is important for contractile endurance. It is currently unknown whether similar regulation exists in human muscle, and the molecular mechanisms underlying PKC-dependent ClC-1 inhibition are unclear. This study first determined whether PKC-dependent ClC-1 inhibition exists in active human muscle, and second, it clarified how PKC alters the gating of human ClC-1 expressed in Xenopus oocytes. In human abdominal and intercostal muscles, repeated AP firing was associated with 30-60% reduction of ClC-1 function, which could be completely prevented by PKC inhibition (1 MUm GF109203X). The role of the PKC-dependent ClC-1 inhibition was evaluated from rheobase currents before and after firing 1000 APs: while rheobase current was well maintained after activity under control conditions it rose dramatically if PKC-dependent ClC-1 inhibition had been prevented with the inhibitor. This demonstrates that the ClC 1 inhibition is important for maintenance of excitability in active human muscle fibres. Oocyte experiments showed that PKC activation lowered the overall open probability of ClC-1 in the voltage range relevant for AP initiation in muscle fibres. More detailed analysis of this reduction showed that PKC mostly affected the slow gate of ClC-1. Indeed, there was no effect of PKC activation in C277S mutated ClC-1 in which the slow gate is effectively locked open. It is concluded that regulation of excitability of active human muscle fibres relies on PKC dependent ClC-1 inhibition via a gating mechanism. PMID- 26857342 TI - GC-MS Metabolite Profiling of Extreme Southern Pinot noir Wines: Effects of Vintage, Barrel Maturation, and Fermentation Dominate over Vineyard Site and Clone Selection. AB - Wine is an extremely complex beverage that contains a multitude of volatile and nonvolatile compounds. This study investiged the effect of vineyard site and grapevine clone on the volatile profiles of commercially produced Pinot noir wines from central Otago, New Zealand. Volatile metabolites in Pinot noir wines produced from five grapevine clones grown on six vineyard sites in close proximity, over two consecutive vintages, were surveyed using gas chromatography mass spectrometry (GC-MS). The raw GC-MS data were processed using parallel factor analysis (PARAFAC2), and final metabolite data were analyzed by principal component analysis (PCA). Winemaking conditions, vintage, and barrel maturation were found to be the most dominant factors. The effects of vineyard site and clone were mostly vintage dependent. Although four compounds including beta citronellol, homovanillyl alcohol, N-(3-methylbutyl)acetamide, and N-(2 phenylethyl)acetamide discriminated the vineyard sites independent of vintage, Pinot noir wines from different clones were only partially discriminated by PCA, and marker compound selection remained challenging. PMID- 26857343 TI - The sociology of childbirth: an autobiographical journey through four decades of research. AB - The sociology of childbirth emerged in the 1970s largely as a result of influences from outside sociology. These included feminism, maternity care activism, the increasing medicalisation of childbirth, and evidence-based health care. This paper uses the author's own sociological 'career' to map a journey through four decades of childbirth research. It demonstrates the importance of social networks and interdisciplinary work, particularly across the medical social science divide and including cross-cultural perspectives, argues that the study of reproduction has facilitated methodological development within the social sciences, and suggests that childbirth remains on the periphery of mainstream sociological concerns. PMID- 26857344 TI - Clinical Relevance of Left Atrial Strain to Predict Recurrence of Atrial Fibrillation after Catheter Ablation: A Meta-Analysis. AB - BACKGROUND: The purpose of this meta-analysis was to analyze the clinical relevance of left atrial (LA) strain to predict recurrence of atrial fibrillation (AF) after catheter ablation (CA). METHODS AND RESULTS: We searched in different databases (Medline, EMBASE, and Cochrane) prospective studies that analyzed LA strain before CA. Eight studies (2 with only paroxysmal AF and 6 with mixed population of paroxysmal and persistent AF) were included in the final analysis (total patient number = 686). Patients with recurrence of AF were principally characterized by lower LA strain in comparison with those without AF recurrence (mean 18.4% [range 8.8-24.5%] versus 25.3% [13.6-32.7%], weighted mean difference -4.89% [95% CI -5.83% to -3.95%], P < 0.001). In addition, receiver operating curves shown that LA strain was strongly associated with recurrence of AF after CA (weighted mean: AUC 0.798 [95% CI 0.700-0.943], cutoff 22.8% [18.8-30%], sensitivity 78% [65-86%], and specificity 75% [66-100%]). In line, these results were similar using LA strain with QRS-analysis and P-analysis as well as using different software package such as Echo-Pac, QLab, TomTec, and VVI. CONCLUSION: In patients with AF candidate for CA, the analysis of the LA using LA strain could be of great usefulness to identify patients with high risk of AF recurrence. Nonetheless, further studies are needed to establish the clinical relevance of LA strain in patients with persistent AF. PMID- 26857346 TI - Mineral requirements of hair sheep in tropical climates. AB - In this study, we evaluated the requirements of calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na) and potassium (K) for sheep hair growth. Experimental diets contained different levels of metabolizable energy [ME; 0.96, 1.28, 1.72, 2.18 and 2.62 Mcal/kg of dry matter, (DM), corresponding to 4.23, 5.64, 7.58, 9.61 and 11.55 MJ/kg DM]. The lambs' hair (n = 48) at 2 months of age presented an average body weight (BW) of 12.05 +/- 1.81 kg. At the beginning of the experiment, eight animals were slaughtered as a reference group to estimate the initial empty body weight and body composition. Net mineral requirements (g/day) ranged from 0.73 to 0.71 g of Ca, 0.51 to 0.49 g of P, 0.026 to 0.026 g of Mg, 0.16 to 0.19 g of Na and 0.15 to 0.13 g of K for animals with a BW ranging from 15 to 30 kg and a daily gain of 100 g. The results of this study indicate that the net macromineral requirements for weight gain in Morada Nova lambs are different from the values commonly recommended by the Agricultural and Food Research Council. PMID- 26857345 TI - Newly developed and validated eosinophilic esophagitis histology scoring system and evidence that it outperforms peak eosinophil count for disease diagnosis and monitoring. AB - Eosinophilic esophagitis (EoE) is diagnosed by symptoms, and at least 15 intraepithelial eosinophils per high power field in an esophageal biopsy. Other pathologic features have not been emphasized. We developed a histology scoring system for esophageal biopsies that evaluates eight features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces (DIS), surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities were scored using a 4-point scale (0 normal; 3 maximum change). Reliability was demonstrated by strong to moderate agreement among three pathologists who scored biopsies independently (P <= 0.008). Several features were often abnormal in 201 biopsies (101 distal, 100 proximal) from 104 subjects (34 untreated, 167 treated). Median grade and stage scores were significantly higher in untreated compared with treated subjects (P <= 0.0062). Grade scores for features independent of eosinophil counts were significantly higher in biopsies from untreated compared with treated subjects (basal zone hyperplasia P <= 0.024 and DIS P <= 0.005), and were strongly correlated (R-square >0.67). Principal components analysis identified three principal components that explained 78.2% of the variation in the features. In logistic regression models, two principal components more closely associated with treatment status than log distal peak eosinophil count (PEC) (R-square 17, area under the curve (AUC) 77.8 vs. R-square 9, AUC 69.8). In summary, the EoE histology scoring system provides a method to objectively assess histologic changes in the esophagus beyond eosinophil number. Importantly, it discriminates treated from untreated patients, uses features commonly found in such biopsies, and is utilizable by pathologists after minimal training. These data provide rationales and a method to evaluate esophageal biopsies for features in addition to PEC. PMID- 26857347 TI - Activation of the Cardiac Renin-Angiotensin System in High Oxygen-Exposed Newborn Rats: Angiotensin Receptor Blockade Prevents the Developmental Programming of Cardiac Dysfunction. AB - Newborn rats exposed to high oxygen (O2), mimicking preterm birth-related neonatal stress, develop later in life cardiac hypertrophy, dysfunction, fibrosis, and activation of the renin-angiotensin system. Cardiac renin angiotensin system activation in O2-exposed adult rats is characterized by an imbalance in angiotensin (Ang) receptors type 1/2 (AT1/2), with prevailing AT1 expression. To study the role of renin-angiotensin system in the developmental programming of cardiac dysfunction, we assessed Ang receptor expression during neonatal high O2 exposure and whether AT1 receptor blockade prevents cardiac alterations in early adulthood. Sprague-Dawley newborn rats were kept with their mother in 80% O2 or room air (control) from days 3 to 10 (P3-P10) of life. Losartan or water was administered by gavage from P8 to P10 (n=9/group). Rats were studied at P3 (before O2 exposure), P5, P10 (end of O2), and P28. Losartan treatment had no impact on growth or kidney development. AT1 and Ang type 2 receptors were upregulated in the left ventricle by high O2 exposure (P5 and P10), which was prevented by Losartan treatment at P10. Losartan prevented the cardiac AT1/2 imbalance at P28. Losartan decreased cardiac hypertrophy and fibrosis and improved left ventricle fraction of shortening in P28 O2-exposed rats, which was associated with decreased oxidation of calcium/calmodulin dependent protein kinase II, inhibition of the transforming growth factor beta/SMAD3 pathway, and upregulation of cardiac angiotensin-converting enzyme 2. In conclusion, short-term Ang II blockade during neonatal high O2 prevents the development of cardiac alterations later in life in rats. These findings highlight the key role of neonatal renin-angiotensin system activation in the developmental programming of cardiac dysfunction induced by deleterious neonatal conditions. PMID- 26857348 TI - New view of population genetics of zooplankton: RAD-seq analysis reveals population structure of the North Atlantic planktonic copepod Centropages typicus. AB - Detection of population genetic structure of zooplankton at medium-to-small spatial scales in the absence of physical barriers has remained challenging and controversial. The large population sizes and high rates of gene flow characteristic of zooplankton have made resolution of geographical differentiation very difficult, especially when using few genetic markers and assuming equilibrium conditions. Next-generation sequencing now allows simultaneous sampling of hundreds to thousands of genetic markers; new analytical approaches allow studies under nonequilibrium conditions and directional migration. Samples of the North Atlantic Ocean planktonic copepod, Centropages typicus, were analysed using restriction site-associated DNA (RAD) sequencing on a PROTON platform. Although prior studies revealed no genetic differentiation of populations across the geographical range of the species, analysis of RAD tags showed significant structure across the North Atlantic Ocean. We also compared the likelihood for models of connectivity among NW Atlantic populations under various directional flow scenarios that replicate oceanographic conditions of the sampled domain. High-density marker sampling with RAD sequencing markedly outperformed other technical and analytical approaches in detection of population genetic structure and characterization of connectivity of this high geneflow zooplankton species. PMID- 26857350 TI - A Review of Three-Dimensional Printing in Tissue Engineering. AB - Recent advances in three-dimensional (3D) printing technologies have led to a rapid expansion of applications from the creation of anatomical training models for complex surgical procedures to the printing of tissue engineering constructs. In addition to achieving the macroscale geometry of organs and tissues, a print layer thickness as small as 20 MUm allows for reproduction of the microarchitectures of bone and other tissues. Techniques with even higher precision are currently being investigated to enable reproduction of smaller tissue features such as hepatic lobules. Current research in tissue engineering focuses on the development of compatible methods (printers) and materials (bioinks) that are capable of producing biomimetic scaffolds. In this review, an overview of current 3D printing techniques used in tissue engineering is provided with an emphasis on the printing mechanism and the resultant scaffold characteristics. Current practical challenges and technical limitations are emphasized and future trends of bioprinting are discussed. PMID- 26857349 TI - Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network. AB - Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of "precision medicine." The February 2015 eMERGE-PGx data release includes sequence-derived data from ~5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine. PMID- 26857352 TI - Intracellular traffic of the lysine and glutamic acid rich protein KERP1 reveals features of endomembrane organization in Entamoeba histolytica. AB - The development of amoebiasis is influenced by the expression of the lysine and glutamic acid rich protein 1 (KERP1), a virulence factor involved in Entamoeba histolytica adherence to human cells. Up to date, it is unknown how the protein transits the parasite cytoplasm towards the plasma membrane, specially because this organism lacks a well-defined endoplasmic reticulum (ER) and Golgi apparatus. In this work we demonstrate that KERP1 is present at the cell surface and in intracellular vesicles which traffic in a pathway that is independent of the ER-Golgi anterograde transport. The intracellular displacement of vesicles enriched in KERP1 relies on the actin-rich cytoskeleton activities. KERP1 is also present in externalized vesicles deposited on the surface of human cells. We further report the interactome of KERP1 with its association to endomembrane components and lipids. The model for KERP1 traffic here proposed hints for the first time elements of the endocytic and exocytic paths of E. histolytica. PMID- 26857351 TI - Ebola vaccine development plan: ethics, concerns and proposed measures. AB - BACKGROUND: The global interest in developing therapies for Ebola infection management and its prevention is laudable. However the plan to conduct an emergency immunization program specifically for healthcare workers using experimental vaccines raises some ethical concerns. This paper shares perspectives on these concerns and suggests how some of them may best be addressed. DISCUSSION: The recruitment of healthcare workers for Ebola vaccine research has challenges. It could result in coercion of initially dissenting healthcare workers to assist in the management of EVD infected persons due to mistaken beliefs that the vaccine offers protection. It could also affect equity and justice. For example, where people who are not skilled health care professionals but who provide care to patients infected with Ebola (such as in home care settings) are not prioritized for vaccination. The possibility of study participants contracting Ebola infection despite the use of experimental vaccine, and the standard of care they would receive, needs to be addressed clearly, transparently and formalized as part of the ethics review process. Future access to study products in view of current status of the TRIPS agreement needs to be addressed. Finally, broad stakeholder engagement at local, regional and international levels needs to be promoted using available communication channels to engage local, regional and international support. These same concerns are applicable for current and future epidemics. Successful Ebola vaccine development research requires concerted efforts at public dialogue to address misconceptions, equity and justice in participant selection, and honest discussions about risks, benefits and future access. Public dialogue about Ebola vaccine research plans is crucial and should be conducted by trusted locals and negotiated between communities, researchers and ethics committees in research study sites. PMID- 26857353 TI - Women's experience of intrapartum transfer from a Western Australian birth centre co-located to a tertiary maternity hospital. AB - BACKGROUND: The aim of this Western Australian study was to describe the overall labour and birth experience of women who were transferred during the first and second stages of labour from a low risk woman-centred, midwifery-led birth centre to a co-located tertiary maternity referral hospital. METHODS: Using a descriptive phenomenological design, fifteen women were interviewed up to 8 weeks post birth (July to October, 2013) to explore their experience of the intrapartum transfer. Giorgi's method of analysis was used. RESULTS: The following themes and subthemes emerged: 1) The midwife's voice with subthemes, a) The calming effect and b) Speaking up on my behalf; 2) In the zone with subthemes, a) Hanging in there and b) Post birth rationalizing; 3) Best of both worlds with subthemes a) The feeling of relief on transfer to tertiary birth suite and b) Returning back to the comfort and familiarity of the birth centre; 4) Lost sense of self; and 5) Lost birth dream with subthemes a) Narrowing of options and b) Feeling of panic. Women found the midwife's voice guided them through the transfer experience and were appreciative of continuity of care. There was a sense of disruption to expectations and disappointment in not achieving the labour and birth they had anticipated. There was however appreciation that the referral facility was nearby and experts were close at hand. The focus of care altered from woman to fetus, making women feel diminished. Women were glad to return to the familiar birth centre after the birth with the opportunity to talk through and fully understand their labour journey which helped them contextualise the transfer as one part of the whole experience. CONCLUSIONS: Findings can inform midwives of the value of a continuity of care model within a birth centre, allowing women both familiarity and peace of mind. Maternity care providers should ensure that the woman remains the focus of care after transfer and understand the significance of effective communication to ensure women are included in all care discussions. PMID- 26857354 TI - Effect of testosterone therapy on the female voice. AB - OBJECTIVES: This prospective study was designed to investigate the effect of testosterone, delivered by subcutaneous implants, on the female voice. METHODS: Ten women who had opted for testosterone therapy were recruited for voice analysis. Voices were recorded prior to treatment and at 3 months, 6 months, and 12 months while on testosterone therapy. Acoustic samples were collected with subjects reading a sentence, reading a paragraph, and participating in a conversation. Significant changes in the voice over time were investigated using a repeated-measures analysis of variance with the fundamental frequency (F0) as a response variable. Demographic variables associated with characteristics of the voice were assessed. RESULTS: There were no significant differences in average F0 related to smoking history, menopausal status, weight, or body mass index. There was no difference in average fundamental speaking frequency (sentence, paragraph, conversation) between the pre-treatment group and any post-treatment group at 3 and 12 months. There was an increase in sentence speech F0 at 6 months. Two of three patients with lower than expected F0 at baseline improved on testosterone therapy. CONCLUSION: Therapeutic levels of testosterone, delivered by subcutaneous implant, had no adverse affect on the female voice including lowering or deepening of the voice. PMID- 26857355 TI - Opinion on Schmidt et al. PMID- 26857356 TI - The reactivity of 1,1-dichloro-2,2-di-tert-butyldiphosphane towards lithiated metal carbonyls: a new entry to phosphanylphosphinidene dimers. AB - Reactions of [Cp*(OC)3M]Li (Cp* = C5Me5, M = Mo, W) towards t-Bu2P-PCl2 lead to the formation of phosphanylphosphinidene dimers [Cp*(OC)3M(eta(2)-t-Bu2P-P)]2 in fairly good yields. The formation of a tetraphosphorus ligand proceeds via reductive dimerization of t-Bu2P-P units. NMR, X-ray investigations and DFT calculations show that the resulting tetraphosphorus ligand has a structure of dication t-Bu2P(+)=P-P=P(+)t-Bu2. PMID- 26857357 TI - Fusion of the HMGA2 and C9orf92 genes in myolipoma with t(9;12)(p22;q14). AB - BACKGROUND: Myolipoma of soft tissue is an extremely rare benign tumor composed of mature adipose tissue and smooth muscle cells. It is found predominantly in women. The cytogenetic and molecular genetic features of myolipomas remain largely unexplored. Here we present the first cytogenetically analyzed myolipoma. METHODS: Cytogenetic and molecular genetic analyses were done on a myolipoma. RESULTS: G-banding analysis of short-term cultured cells from the myolipoma yielded a karyotype with a single clonal chromosome abnormality: 46,XX,t(9;12)(p22;q14). Fluorescence in situ hybridization experiments demonstrated that HMGA2 (in 12q14) was rearranged. Molecular genetic analysis showed that the translocation resulted in fusion of HMGA2 with the C9orf92 gene (from 9p22). The HMGA2-C9orf92 fusion transcript would code for a putative protein containing amino acid residues 1-94 of HMGA2 and 6 amino acid residues from the out-of-frame fusion with exon 4 of C9orf92. CONCLUSION: The pattern of HMGA2 rearrangement in the present case of myolipoma is similar to what is found in other benign connective tissue tumor types, including lipomas, i.e., disruption of the HMGA2 locus leaves intact exons which encode the AT-hook domains but separates them from the 3'-terminal part of the gene. Whether any genetic features differentiate myolipomas from regular lipomas with HMGA2 involvement is a question that cannot be answered until more cases of the former tumor type are subjected to genetic analysis. PMID- 26857358 TI - Predictors of place of death in South West Scotland 2000-2010: Retrospective cohort study. AB - BACKGROUND: Surveys suggest most people would prefer to die in their own home. AIM: To examine predictors of place of death over an 11-year period between 2000 and 2010 in Dumfries and Galloway, south west Scotland. DESIGN: Retrospective cohort study. SETTING/PARTICIPANTS: 19,697 Dumfries and Galloway residents who died in the region or elsewhere in Scotland. We explored the relation between age, gender, cause of death (cancer, respiratory, ischaemic heart disease, stroke and dementia) and place of death (acute hospital, cottage hospital, residential care and home) using regression models to show differences and trends. The main acute hospital in the region had a specialist palliative care unit. RESULTS: Fewer people died in their own homes (23.2% vs 29.6%) in 2010 than in 2000. Between 2007 and 2010, men were more likely to die at home than women (p < 0.001), while both sexes were less likely to die at home as they became older (p < 0.001) and in successive calendar years (p < 0.003). Older people with dementia as the cause of death were particularly unlikely to die in an acute hospital and very likely to die in a residential home (p < 0.001). Between 2007 and 2010, an increasing proportion of acute hospital deaths occurred in the specialist palliative care unit (6% vs 11% of all deaths in the study). CONCLUSION: The proportion of people dying at home fell during our survey. Place of death was strongly associated with age, calendar year and cause of death. A mismatch remains between stated preference for place of death and where death occurs. PMID- 26857359 TI - 'I think you just learnt as you went along' - community clergy's experiences of and attitudes towards caring for dying people: A pilot study. AB - BACKGROUND: Spiritual distress is a factor associated with poor outcomes at the end of life. Timely interventions, assessing and meeting spiritual distress, among patients are contained within nationally agreed guidance. Community clergy are well placed to work alongside healthcare professionals and chaplains to meet spiritual needs. METHODS: Qualitative interviews among Christian clergy in two South East London boroughs and a self-completed Death Anxiety Questionnaire. RESULTS: Fourteen clergy were interviewed from six Christian denominations. Participants described their experiences of ordination training and how helpful this had been for their work among Christian communities. Respondents were invited to discuss their knowledge of and involvement with palliative care services. Each interviewee also accounted for their understanding of pastoral care and spiritual care and considered whether any differences existed between these terms and, if so, what they were. Overall, clergy lacked any detailed formal training and had little experience of working with or relating to palliative care providers. Recommendations are made to improve educational opportunities and working relationships. CONCLUSIONS: Creating opportunities for clergy and palliative care staff to meet and undertake shared training will enhance the quality and level of care for people dying at home who wish to receive spiritual support. Enabling clergy to develop links with local palliative care centres will enhance confidence for both clergy and staff. PMID- 26857360 TI - The meaning of self-reported death anxiety in advanced cancer. AB - BACKGROUND: Death anxiety is important but understudied in palliative care. New self-report measurements have been developed, but their interpretation and clinical utility may not be evident. AIM: To inform our understanding of death anxiety in patients with advanced cancer by exploring the relationship between this self-reported symptom and its clinical presentation. DESIGN: Participants were part of a psychotherapy trial in advanced cancer. First therapy session transcripts were analyzed using interpretive description in patients reporting low, moderate, and high death anxiety on the Death and Dying Distress Scale (DADDS). SETTING/PARTICIPANTS: A total of 16 participants (10 women and 6 men) with advanced or metastatic cancer were sampled from the Princess Margaret Cancer Centre, Toronto, Canada. Six participants reported low death anxiety scores (Death and Dying Distress Scale: 0-19), five moderate (Death and Dying Distress Scale: 20-50), and five high (Death and Dying Distress Scale: 51-75). RESULTS: The low death anxiety group exhibited psychological readiness for death, or contrastingly, non-reflectiveness about death. The moderate group recognized the imminence of mortality, which impacted treatment decisions and future plans. Prior experience with death was discussed as raising the salience of mortality. The high group felt dominated by powerful emotions and could not make sense of their situation. Their distress was exacerbated by substantial relational concerns. CONCLUSION: Self-reported death anxiety is affected by the awareness and ability to reflect on mortality. Death and Dying Distress Scale scores may facilitate exploration of this symptom as part of a clinical assessment and may serve to guide treatment approaches. Greater attention to death anxiety is consistent with and recommended by contemporary approaches to palliative care. PMID- 26857363 TI - Clearance of cerebrospinal fluid JCV DNA with mirtazapine in a patient with progressive multifocal leukoencephalopathy and sarcoidosis. AB - Progressive multifocal leukoencephalopathy (PML) is a severe encephalic demyelinating disease associated with JC virus (JCV) reactivation that occurs mostly in patients with immune disorders. Patients affected by sarcoidosis are at risk for developing PML both for leukocyte dysfunction and for receiving immunosuppressive medications: delayed diagnosis and high-dose corticosteroids are associated with a reduced survival. Although no specific treatment for PML exists, several therapeutic possibilities have been assessed with uncertain benefits (5HT2a receptor inhibitors are active in vitro against JCV): the cornerstone of sarcoidosis-associated PML is immunosuppressants withdrawal.We report the case of a female patient affected by systemic sarcoidosis for 30 years receiving low-dose corticosteroids (5 mg every other day). Due to memory impairment an MRI was performed showing three T2 hyperintense lesions involving white matter. Cerebrospinal fluid JCV PCR (845 copies/ml), neuropathological examination and immunohistochemistry (SV40 protein and JCV DNA positivity) on brain biopsy confirmed PML. Mirtazapine 15 mg was started while prednisone treatment was continued. 3 and 6 months later cognitive performances improved and brain MRIs were stable while cerebrospinal fluid JCV DNA was undetectable (6 months later). In conclusion the diagnosis of PML in patients with sarcoidosis is challenging given the overlapping presentation; the use of 5HT2a receptor antagonists deserves further studying in patients needing immunosuppressant drugs to control their dysimmune disease. PMID- 26857364 TI - Goals and Objectives for the Psychiatry Resident On-Call Experience: A Survey of Psychiatry Training Programs. PMID- 26857361 TI - Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers. AB - Despite significant advances in early detection and treatment, breast cancer still remains a major cause of morbidity and mortality for women. Our understanding of the molecular heterogeneity of the disease has significantly expanded over the past decade and the role of cell cycle signaling in both breast cancer oncogenesis and anti-estrogen resistance has gained increasing attention. The mammalian cell cycle is driven by a complex interplay between cyclins and their associated cyclin-dependent kinase (CDK) partners, and dysregulation of this process is one of the hallmarks of cancer. Despite this, initial results with broadly acting CDK inhibitors were largely disappointing. However, recent preclinical and phase I/II clinical studies using a novel, oral, reversible CDK4/6 inhibitor, palbociclib (PD-0332991), have validated the role of CDK4/6 as a potential target in estrogen receptor-positive (ER+) breast cancers. This review highlights our current understanding of CDK signaling in both normal and malignant breast tissues, with special attention placed on recent clinical advances in inhibition of CDK4/6 in ER+ disease. PMID- 26857365 TI - Practices in antenatal counseling for extremely premature infants amongst European trainees. AB - There is no international consensus on content and process regarding antenatal counseling in extreme prematurity. The need for adequate training is increasingly recognized. This descriptive study evaluates current practice in antenatal counseling amongst European trainees using an online survey. Focusing on the process, the majority of respondents did not have a medical consensus guideline. Seven percent of the trainees received some formal training. Focusing on the content, about half of the subjects did not mention any statistics about mortality. CONCLUSION: We observed wide variation in actual content and organization in antenatal counseling in Europe amongst European trainees in neonatology. PMID- 26857366 TI - The distinct clinical features and prognosis of the CD10+MUM1+ and CD10-Bcl6-MUM1 diffuse large B-cell lymphoma. AB - Using an immunohistochemistry (IHC) based method, diffuse large B-cell lymphoma (DLBCL) can be classified into germinal center B-cell (GCB) and non-GCB subtypes. However, the prognostic value of Hans algorithm was contradictory in the literature. Using IHC and fluorescence in situ hybridization, we analyzed the antibodies applied in Hans algorithm and other genetic factors in 601 DLBCL patients and prognostic value of Hans algorithm in 306 cases who were treated with chemoimmunotherapy. The results showed that patients with GCB subtype have better overall survival (OS) and progression-free survival (PFS) than non-GCB cases. However, to some extent, double positive (CD10(+)MUM1(+), DP) and triple negative (CD10(-)Bcl6(-)MUM(-), TN) showed different clinical characteristics and prognosis to others that were assigned to the same cell-of-origin group. The DP group showed similar OS (median OS: both not reached, P = 0.3650) and PFS (median PFS: 47.0 vs. 32.7 months, P = 0.0878) with the non-GCB group while the TN group showed similar OS (median OS: both not reached, P = 0.9278) and PFS (median PFS: both not reached, P = 0.9420) with the GCB group. In conclusion, Recognition of specific entities in Hans algorithm could help us to accurately predict outcome of the patients and choose the best clinical management for them. PMID- 26857367 TI - Mini-nephroscope combined with pressure suction: an effective tool in MPCNL for intrarenal stones in patients with urinary tract infections. AB - We report our experience with a mini-nephroscope connected to pressure suction as a modified minimally invasive percutaneous nephrolithotomy (MPCNL) technique to manage intrarenal stones in patients with a urinary tract infection (UTI). We used a mini-nephroscope connected to pressure suction to aspirate infected urine and reduce intrapelvic pressure. From January 2010 to June 2014, we treated 683 patients with intrarenal stones and UTI with this modified MPCNL technique in our department (Group A). Patients with an intrarenal stone and without UTI treated by this modified MPCNL (Group B, N = 422) and patients with an intrarenal stone and UTI but treated by traditional MCPNL without pressure suction (Group C, N = 95) were collected as control groups. In group A, 635 of the 683 patients (93 %) had a positive urine culture preoperatively and the other 48 patients (7 %) were diagnosed with pyonephrosis intraoperatively. The mean stone bulk was 843 +/- 151.4 mm(2) and mean operative time was 71.0 +/- 11.5 min. The mean stone bulk and operative time were similar to those of group B and group C. However, the rates of infectious complications for groups A (6.4 %) and B (4.9 %) were similar, but higher in group C (28.4 %). In group A, only 38 patients had fever and 6 patients developed sepsis. None of the patients showed progression to multiple organ dysfunction syndrome or died in all of patients. Our results demonstrated that this modified MPCNL technique is safe, feasible, and efficient for managing intrarenal calculi in patients with an UTI. PMID- 26857368 TI - Concomitant production of xylanases and cellulases from Trichoderma longibrachiatum MDU-6 selected for the deinking of paper waste. AB - Sixty fungal cultures were isolated from agricultural soil, industrial soil, forest canopy soil having decomposed leaf litter and compost samples collected from different regions of India. Fifteen fungal cultures were selected qualitatively for the production of xylanase and cellulases and were identified employing ITS, NS and MNS primers. The enzyme cocktail consisting of 3811 IU g( 1) of xylanase and 9.9 IU g(-1) of cellulase from Trichoderma longibrachiatum MDU 6 was selected quantitatively for the deinking of diverse paper wastes. The enzyme production increased two fold when produced at tray level in comparison with flasks. The enzyme cocktail was effective in the deinking of old newspaper samples with significant removal of chromophores, phenolics and hydrophobic compounds and less sugar loss. While in case of examination papers and laser printed papers, ink removal was not very significant. Moreover, the sugar loss was significantly high in case of examination papers. The deinking results were further confirmed with FTIR analysis. Deinked newspaper pulp sample shows brightness of 52%, which was 9.6% high than its control sample. The ERIC value for deinked newspaper pulp was found to be 655.9 ppm. Thereafter, the deinked newspaper pulp was examined under light microscope after differential staining with safranin and malachite green and also examined under scanning and transmission electron microscope, which revealed fibrillation and perforation. PMID- 26857369 TI - Plant extract-mediated biogenic synthesis of silver, manganese dioxide, silver doped manganese dioxide nanoparticles and their antibacterial activity against food- and water-borne pathogens. AB - Silver nanoparticles (AgNPs), manganese dioxide nanoparticles (MnO2NPs) and silver-doped manganese dioxide nanoparticles (Ag-doped MnO2NPs) were synthesized by simultaneous green chemistry reduction approach. Aqueous extract from the leaves of medicinally important plant Cucurbita pepo was used as reducing and capping agents. Various characterization techniques were carried out to affirm the formation of nanoparticles. HR-TEM analysis confirmed the size of nanoparticles in the range of 15-70 nm and also metal doping was confirmed through XRD and EDS analyses. FT-IR analysis confirmed that the presence of biomolecules in the aqueous leaves extract was responsible for nanoparticles synthesis. Further, the concentration of metals and their doping in the reaction mixture was achieved by ICP-MS. The growth curve and well diffusion study of synthesized nanoparticles were performed against food- and water-borne Gram positive and Gram-negative bacterial pathogens. The mode of interaction of nanoparticles on bacterial cells was demonstrated through Bio-TEM analysis. Interestingly, AgNPs and Ag-doped MnO2NPs showed better antibacterial activity against all the tested bacterial pathogens; however, MnO2NPs alone did not show any antibacterial properties. Hence, AgNPs and Ag-doped MnO2NPs synthesized from aqueous plant leaves extract may have important role in controlling various food spoilage caused by bacteria. PMID- 26857370 TI - The influence of polymeric membrane gas spargers on hydrodynamics and mass transfer in bubble column bioreactors. AB - Gas sparging performances of a flat sheet and tubular polymeric membranes were investigated in 3.1 m bubble column bioreactor operated in a semi batch mode. Air water and air-CMC (Carboxymethyl cellulose) solutions of 0.5, 0.75 and 1.0 % w/w were used as interacting gas-liquid mediums. CMC solutions were employed in the study to simulate rheological properties of bioreactor broth. Gas holdup, bubble size distribution, interfacial area and gas-liquid mass transfer were studied in the homogeneous bubbly flow hydrodynamic regime with superficial gas velocity (U(G)) range of 0.0004-0.0025 m/s. The study indicated that the tubular membrane sparger produced the highest gas holdup and densely populated fine bubbles with narrow size distribution. An increase in liquid viscosity promoted a shift in bubble size distribution to large stable bubbles and smaller specific interfacial area. The tubular membrane sparger achieved greater interfacial area and an enhanced overall mass transfer coefficient (K(L)a) by a factor of 1.2-1.9 compared to the flat sheet membrane. PMID- 26857371 TI - Development of a floating photobioreactor with internal partitions for efficient utilization of ocean wave into improved mass transfer and algal culture mixing. AB - Culturing microalgae in the ocean has potentials that may reduce the production cost and provide an option for an economic biofuel production from microalgae. The ocean holds great potentials for mass microalgal cultivation with its high specific heat, mixing energy from waves, and large cultivable area. Suitable photobioreactors (PBRs) that are capable of integrating marine energy into the culture systems need to be developed for the successful ocean cultivation. In this study, prototype floating PBRs were designed and constructed using transparent low-density polyethylene film for microalgal culture in the ocean. To improve the mixing efficiency, various types of internal partitions were introduced within PBRs. Three different types of internal partitions were evaluated for their effects on the mixing efficiency in terms of mass transfer (k(L)a) and mixing time in the PBRs. The partition type with the best mixing efficiency was selected, and the number of partitions was varied from one to three for investigation of its effect on mixing efficiency. When the number of partitions is increased, mass transfer increased in proportion to the number of partitions. However, mixing time was not directly related to the number of partitions. When a green microalga, Tetraselmis sp. was cultivated using PBRs with the selected partition under semi-continuous mode in the ocean, biomass and fatty acid productivities in the PBRs were increased by up to 50 % and 44% at high initial cell density, respectively, compared to non-partitioned ones. The results of internally partitioned PBRs demonstrated potentials for culturing microalgae by efficiently utilizing ocean wave energy into culture mixing in the ocean. PMID- 26857372 TI - Comprehensive analysis of TCP transcription factors and their expression during cotton (Gossypium arboreum) fiber early development. AB - TCP proteins are plant-specific transcription factors implicated to perform a variety of physiological functions during plant growth and development. In the current study, we performed for the first time the comprehensive analysis of TCP gene family in a diploid cotton species, Gossypium arboreum, including phylogenetic analysis, chromosome location, gene duplication status, gene structure and conserved motif analysis, as well as expression profiles in fiber at different developmental stages. Our results showed that G. arboreum contains 36 TCP genes, distributing across all of the thirteen chromosomes. GaTCPs within the same subclade of the phylogenetic tree shared similar exon/intron organization and motif composition. In addition, both segmental duplication and whole-genome duplication contributed significantly to the expansion of GaTCPs. Many these TCP transcription factor genes are specifically expressed in cotton fiber during different developmental stages, including cotton fiber initiation and early development. This suggests that TCP genes may play important roles in cotton fiber development. PMID- 26857373 TI - Genetic architecture underlying host choice differentiation in the sympatric host races of Lochmaea capreae leaf beetles. AB - Speciation in herbivorous insects has received considerable attention during the last few decades. Much of this group's diversity originates from adaptive population divergence onto different host plants, which often involves the evolution of specialized patterns of host choice behaviour. Differences in host choice often translates directly into divergence in mating sites, and therefore positive assortative mating will be created which will act as a strong barrier to gene flow. In this study, we first explored whether host choice is a genetically determined trait in the sympatric willow and birch host races of the leaf feeding beetle Lochmaea capreae, or whether larval experience influences adult host choice. Once we had established that host choice is a genetically based trait we determined its genetic architecture. To achieve this, we employed a reciprocal transplant design in which offspring from pure willow and birch cross-types, F1, F2 and backcrosses were raised on each host plant and their preference was determined upon reaching adulthood. We then applied joint-scaling analysis to uncover the genetic architecture of host preference. Our results suggest that rearing host does not have a pronounced effect on adult's host choice; rather the segregation pattern implies the existence of genetic loci affecting host choice in these host races. The joint-scaling analysis revealed that population differences in host choice are mainly influenced by the contribution of additive genetic effects and also maternally inherited cytoplasmic effects. We explore the implications of our findings for evolutionary dynamics of sympatric host race formation and speciation. PMID- 26857374 TI - Aberrant Methylation of RASSF1A Closely Associated with HNSCC, a Meta-Analysis. AB - The RAS association domain family protein 1a (RASSF1A), a tumor suppressor gene at 3p21.3, plays a very important role in various cancers, including the head and neck squamous cell carcinoma (HNSCC). Hypermethylation of CpG islands in the RASSF1A promoter region contribute to epigenetic inactivation. However, the association between RASSF1A promoter methylation and HNSCC remains unclear and controversial. Therefore, a meta-analysis was performed in the study to identify the association. We identified the eligible studies through searching PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure (CNKI) databases with a systematic searching strategy. The information on characteristics of each study and prevalence of RASSF1A methylation were collected. Pooled odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Meta-regression was performed to analyze heterogeneity and funnel plots were applied to evaluate publication bias. A total of 550 HNSCC patients and 404 controls from twelve eligible studies were included in the meta analysis. Overall, a significant association was observed between RASSF1A methylation status and HNSCC risk under a random-effects model (OR = 2.93, 95% CI: 1.58-5.46). There was no significant publication bias observed. The meta analysis suggested that there was a significant association between aberrant RASSF1A methylation and HNSCC. PMID- 26857376 TI - Positive Perceptions of Genital Appearance and Feeling Sexually Attractive: Is It a Matter of Sexual Esteem? AB - The present study examined the relationship between perceptions of genital appearance and self-perceived sexual attractiveness. The study sample included men and women (aged 18-45 years, M = 23.7, SD = 4.98) who identified as heterosexual (n = 1017), gay or lesbian (n = 1225), or bisexual (n = 651). Participants responded to an online survey assessing their self-perceived sexual attractiveness, genital self-image, genital self-consciousness during sexual activity, and sexual esteem. Based on previous findings, we hypothesized a positive link between genital self-perceptions and self-perceived sexual attractiveness, with sexual esteem acting as a mediator. We tested this hypothesis using structural equation modeling. Analyses revealed a significant association between both genital self-image and genital self-consciousness and self-perceived sexual attractiveness. However, these relationships were at least partially mediated by sexual esteem, across both gender and sexual orientation. The findings suggest that, regardless of gender or sexual orientation, individuals who maintain a positive genital self-image or lack genital self consciousness, are more likely to experience greater sexual esteem, and in turn, feel more sexually attractive. The findings have implications for the importance of genital appearance perceptions and improving individuals' sexual esteem and self-perceived sexual attractiveness. PMID- 26857375 TI - Exosomal transfer of miR-30a between cardiomyocytes regulates autophagy after hypoxia. AB - Recent studies have indicated a protective role of physiological autophagy in ischemic heart disease. However, the underlying mechanisms of autophagy regulation after ischemia are poorly understood. Exosomes are nano-sized vesicles released from cells that play critical roles in mediating cell-to-cell communication through the transfer of microRNAs. In this study, we observed that miR-30a was highly enriched in exosomes from the serum of acute myocardial infarction (AMI) patients in vivo and culture medium of cardiomyocytes after hypoxic stimulation in vitro. We also found that hypoxia inducible factor (HIF) 1alpha regulates miR-30a, which efficiently transferred via exosomes between cardiomyocytes after hypoxia. Inhibition of miR-30a or release of exosomes increased the expression of the core autophagy regulators beclin-1, Atg12, and LC3II/LC3I, which contributed to maintaining the autophagic response in cardiomyocytes after hypoxia. Taken together, the present study showed that exosomes from hypoxic cardiomyocytes regulate autophagy by transferring miR-30a in a paracrine manner, which revealed a new pathway of autophagy regulation that might comprise a promising strategy to treat ischemic heart disease. KEY MESSAGES: miR-30a is highly enriched in exosomes from the serum of AMI patients. Hypoxia induces miR-30a upregulation and enrichment into exosomes. MiR-30a is efficiently transferred via exosomes between hypoxic cardiomyocytes. Inhibition of exosome release contributes to maintaining of autophagy after hypoxia. Inhibition of miR-30a augments autophagy after hypoxia. PMID- 26857377 TI - Pupillary Response as an Age-Specific Measure of Sexual Interest. AB - In the visual processing of sexual content, pupil dilation is an indicator of arousal that has been linked to observers' sexual orientation. This study investigated whether this measure can be extended to determine age-specific sexual interest. In two experiments, the pupillary responses of heterosexual adults to images of males and females of different ages were related to self reported sexual interest, sexual appeal to the stimuli, and a child molestation proclivity scale. In both experiments, the pupils of male observers dilated to photographs of women but not men, children, or neutral stimuli. These pupillary responses corresponded with observer's self-reported sexual interests and their sexual appeal ratings of the stimuli. Female observers showed pupil dilation to photographs of men and women but not children. In women, pupillary responses also correlated poorly with sexual appeal ratings of the stimuli. These experiments provide initial evidence that eye-tracking could be used as a measure of sex specific interest in male observers, and as an age-specific index in male and female observers. PMID- 26857378 TI - Automatic Direction of Spatial Attention to Male Versus Female Stimuli: A Comparison of Heterosexual Men and Women. AB - Abundant research has shown that men's sexual attractions are more category specific in relation to gender than women's are. We tested whether the early automatic allocation of spatial attention reflects these sexual attractions. The dot-probe task was used to assess whether spatial attention was attracted to images of either male or female models that were naked or partially clothed. In Experiment 1, men were faster if the target appeared after the female stimulus, whereas women were equally quick to respond to targets after male or female stimuli. In Experiment 2, neutral cues were introduced. Men were again faster to female images in comparison to male or neutral images, but showed no bias on the male versus neutral test. Women were faster to both male and female pictures in comparison to neutral pictures. However, in this experiment they were also faster to female pictures than to male pictures. The results suggest that early attentional processes reveal category-specific interest to the preferred sexual category for heterosexual men, and suggest that heterosexual women do not have category-specific guidance of attentional mechanisms. The technique may have promise in measuring sexual interest in other situations where participants may not be able, or may not be willing, to report upon their sexual interests (e.g., assessment of paedophilic interest). PMID- 26857380 TI - Effects of Intrinsic and Extrinsic Host Mortality on Disease Spread. AB - The virulent effects of a pathogen on host fecundity and mortality (both intrinsic and extrinsic mortality due to predation) often increase with the age of infection. Age of infection often is also correlated with parasite fitness, in terms of the number of both infective propagules produced and the between-host transmission rate. We introduce a four-population partial differential equations (PDE) model to investigate the invasibility and prevalence of an obligately killing fungal parasite in a zooplankton host as they are embedded in an ecological network of predators and resources. Our results provide key insights into the role of ecological interactions that vary with the age of infection. First, selective predation, which is known both theoretically and empirically to reduce disease prevalence, does not always limit disease spread. This condition dependency relies on the timing and intensity of selective predation and how that interacts with the direct effects of the parasite on host mortality. Second, low host resources and intense predation can prevent disease spread, but once conditions allow the invasion of the parasite, the qualitative dynamics of the system do not depend on the intensity of the selective predation. Third, a comparison of the PDE model with a model based on ordinary differential equations (ODE model) reveals a parametrization for the ODE version that yields an endemic steady state and basic reproductive ratio that are identical to those in the PDE model. Our results highlight the complexity of resource-host-parasite-predator interactions and suggest the need for additional data-theory coupling exploring how community ecology influences the spread of infectious diseases. PMID- 26857379 TI - Body Dissatisfaction Among Sexual Minority Men: Psychological and Sexual Health Outcomes. AB - Body dissatisfaction is common among sexual minority (i.e., gay and bisexual) men; however, few studies have investigated the relationship between body dissatisfaction and psychosexual health variables among this population. The data that do exist are exclusively cross-sectional, casting uncertainty regarding temporal associations. Thus, the aims of the current study were to assess the prospective relationship between body dissatisfaction and psychological and sexual health outcomes. Participants were 131 gay and bisexual men who completed a battery of self-report measures across two time points (baseline and 3-month follow-up), including assessment of body dissatisfaction, depressive symptoms, and sexual health variables (sexual self-efficacy and sexual anxiety). Generalized linear modeling was employed to assess the prospective relationship between body dissatisfaction and outcomes variables, accounting for non-normal distributions. Body dissatisfaction significantly predicted elevated depressive symptoms (B = .21, p = .01), lower sexual self-efficacy (B = -.22, p = .04), and elevated sexual anxiety (B = .05, p = .03). Elevated body dissatisfaction is prospectively associated with negative psychological and sexual health outcomes. Given the high prevalence of body image concerns in sexual minority men, depression and/or HIV/STI prevention programs may benefit from routinely assessing for body dissatisfaction among this population, and addressing those who report concerns. PMID- 26857381 TI - Structural modification of P-glycoprotein induced by OH radicals: Insights from atomistic simulations. AB - This study reports on the possible effects of OH radical impact on the transmembrane domain 6 of P-glycoprotein, TM6, which plays a crucial role in drug binding in human cells. For the first time, we employ molecular dynamics (MD) simulations based on the self-consistent charge density functional tight binding (SCC-DFTB) method to elucidate the potential sites of fragmentation and mutation in this domain upon impact of OH radicals, and to obtain fundamental information about the underlying reaction mechanisms. Furthermore, we apply non-reactive MD simulations to investigate the long-term effect of this mutation, with possible implications for drug binding. Our simulations indicate that the interaction of OH radicals with TM6 might lead to the breaking of C-C and C-N peptide bonds, which eventually cause fragmentation of TM6. Moreover, according to our simulations, the OH radicals can yield mutation in the aromatic ring of phenylalanine in TM6, which in turn affects its structure. As TM6 plays an important role in the binding of a range of cytotoxic drugs with P-glycoprotein, any changes in its structure are likely to affect the response of the tumor cell in chemotherapy. This is crucial for cancer therapies based on reactive oxygen species, such as plasma treatment. PMID- 26857384 TI - Erratum: "Recruitment Viscoelasticity of the Tendon" [ASME J. Biomech. Eng., 2009, 131(11), p. 111008]. PMID- 26857382 TI - Influence of physical fitness on cardio-metabolic risk factors in European children. The IDEFICS study. AB - OBJECTIVE: The aim of the study was to assess the associations of individual and combined physical fitness components with single and clustering of cardio metabolic risk factors in children. SUBJECTS/METHODS: This 2-year longitudinal study included a total of 1635 European children aged 6-11 years. The test battery included cardio-respiratory fitness (20-m shuttle run test), upper-limb strength (handgrip test), lower-limb strength (standing long jump test), balance (flamingo test), flexibility (back-saver sit-and-reach) and speed (40-m sprint test). Metabolic risk was assessed through z-score standardization using four components: waist circumference, blood pressure (systolic and diastolic), blood lipids (triglycerides and high-density lipoprotein) and insulin resistance (homeostasis model assessment). Mixed model regression analyses were adjusted for sex, age, parental education, sugar and fat intake, and body mass index. RESULTS: Physical fitness was inversely associated with clustered metabolic risk (P<0.001). All coefficients showed a higher clustered metabolic risk with lower physical fitness, except for upper-limb strength (beta=0.057; P=0.002) where the opposite association was found. Cardio-respiratory fitness (beta=-0.124; P<0.001) and lower-limb strength (beta=-0.076; P=0.002) were the most important longitudinal determinants. The effects of cardio-respiratory fitness were even independent of the amount of vigorous-to-moderate activity (beta=-0.059; P=0.029). Among all the metabolic risk components, blood pressure seemed not well predicted by physical fitness, while waist circumference, blood lipids and insulin resistance all seemed significantly predicted by physical fitness. CONCLUSION: Poor physical fitness in children is associated with the development of cardio-metabolic risk factors. Based on our results, this risk might be modified by improving mainly cardio-respiratory fitness and lower-limb muscular strength. PMID- 26857385 TI - 2- and 3-dimensional synthetic large-scale de novo patterning by mammalian cells through phase separation. AB - Synthetic biology provides an opportunity for the construction and exploration of alternative solutions to biological problems - solutions different from those chosen by natural life. To this end, synthetic biologists have built new sensory systems, cellular memories, and alternative genetic codes. There is a growing interest in applying synthetic approaches to multicellular systems, especially in relation to multicellular self-organization. Here we describe a synthetic biological system that confers large-scale de novo patterning activity on 2-D and 3-D populations of mammalian cells. Instead of using the reaction-diffusion mechanisms common in real embryos, our system uses cadherin-mediated phase separation, inspired by the known phenomenon of cadherin-based sorting. An engineered self-organizing, large-scale patterning system requiring no prior spatial cue may be a significant step towards the construction of self-assembling synthetic tissues. PMID- 26857383 TI - Effectiveness of Remote Patient Monitoring After Discharge of Hospitalized Patients With Heart Failure: The Better Effectiveness After Transition -- Heart Failure (BEAT-HF) Randomized Clinical Trial. AB - IMPORTANCE: It remains unclear whether telemonitoring approaches provide benefits for patients with heart failure (HF) after hospitalization. OBJECTIVE: To evaluate the effectiveness of a care transition intervention using remote patient monitoring in reducing 180-day all-cause readmissions among a broad population of older adults hospitalized with HF. DESIGN, SETTING, AND PARTICIPANTS: We randomized 1437 patients hospitalized for HF between October 12, 2011, and September 30, 2013, to the intervention arm (715 patients) or to the usual care arm (722 patients) of the Better Effectiveness After Transition-Heart Failure (BEAT-HF) study and observed them for 180 days. The dates of our study analysis were March 30, 2014, to October 1, 2015. The setting was 6 academic medical centers in California. Participants were hospitalized individuals 50 years or older who received active treatment for decompensated HF. INTERVENTIONS: The intervention combined health coaching telephone calls and telemonitoring. Telemonitoring used electronic equipment that collected daily information about blood pressure, heart rate, symptoms, and weight. Centralized registered nurses conducted telemonitoring reviews, protocolized actions, and telephone calls. MAIN OUTCOMES AND MEASURES: The primary outcome was readmission for any cause within 180 days after discharge. Secondary outcomes were all-cause readmission within 30 days, all-cause mortality at 30 and 180 days, and quality of life at 30 and 180 days. RESULTS: Among 1437 participants, the median age was 73 years. Overall, 46.2% (664 of 1437) were female, and 22.0% (316 of 1437) were African American. The intervention and usual care groups did not differ significantly in readmissions for any cause 180 days after discharge, which occurred in 50.8% (363 of 715) and 49.2% (355 of 722) of patients, respectively (adjusted hazard ratio, 1.03; 95% CI, 0.88-1.20; P = .74). In secondary analyses, there were no significant differences in 30-day readmission or 180-day mortality, but there was a significant difference in 180-day quality of life between the intervention and usual care groups. No adverse events were reported. CONCLUSIONS AND RELEVANCE: Among patients hospitalized for HF, combined health coaching telephone calls and telemonitoring did not reduce 180-day readmissions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01360203. PMID- 26857388 TI - Prognostic value of multiple biomarkers for cardiovascular mortality in adult congenital heart disease: comparisons of single-/two-ventricle physiology, and systemic morphologically right/left ventricles. AB - Although there are many biomarkers for heart failure, limited data are available regarding their prognostic value in adult congenital heart disease (ACHD). We investigated the potential of various biomarkers to predict ACHD mortality in a single-center, retrospective cohort study. Blood levels of neurohormones [angiotensin II, endothelin-1 (ET-1), norepinephrine (NE), aldosterone, and plasma renin activity]; inflammatory biomarkers [high-sensitivity C-reactive protein (hs-CRP), high-sensitivity tumor necrosis factor, soluble TNF receptor type I and II (sTNF-RI and sTNF-RII), and interleukin-6 (IL-6)]; and brain natriuretic peptide (BNP) were measured in 103 ACHD patients (median age 28 years). Subjects were divided into patients with single-ventricle physiology (SV group, n = 61) and those with two-ventricle physiology (TV group, n = 42); and into patients with a systemic right ventricle (SRV group, n = 25) and those with a systemic left ventricle (SLV group, n = 78). During a median follow-up period of 6.5 years, 12 patients (11 %) died of acute decompensated heart failure (ADHF). Predictive biomarkers, which are related to the New York Heart Association class and cardiothoracic ratio, were as follows: elevated levels of BNP, ET-1, sTNF-RI, NE, and IL-6 in the overall patient group; IL-6, NE, hs-CRP, BNP, and ET-1 in the TV group; BNP and ET-1 in the SV group; BNP, NE, hs-CRP, sTNF-RI, IL-6, and ET-1 in the SLV group. Elevated levels of ET-1 in SRV groups were slightly although not significantly associated with these. Various clinical biomarkers are associated with ADHF mortality in ACHD patients. The most prominent mortality predictors in biomarker profiles may vary according to differences in ventricular physiology and systemic ventricle morphology. PMID- 26857387 TI - TGFbeta3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis. AB - The matrix-specific protein periostin (POSTN) is up-regulated in human cancers and associated with cancer growth, metastasis and angiogenesis. Although the stroma of cancer tissues is the main source of POSTN, it is still unclear how POSTN plays a role to facilitate the interplay between cancer cells and cancer associated fibroblasts (CAFs) in head and neck cancer (HNC), thereby promoting tumorigenesis via modifying the tumor microenvironment. Herein, we have performed studies to investigate POSTN and its role in HNC microenvironment. Our results indicated that POSTN was significantly up-regulated in HNCs, especially in the tissues with lymph node metastasis. Moreover, POSTN was highly enriched in the stroma of cancer tissues and produced mainly by CAFs. More importantly, we have pinpointed TGF-beta3 as the major upstream molecular that triggers the induction of POSTN in CAFs. As such, during the interaction between fibroblasts and cancer cells, the increased stromal POSTN induced by TGF-beta3 directly accelerated the growth, migration and invasion of cancer cells. Hence, our study has provided a novel modulative role for POSTN on HNC progression and further reveals POSTN as an effective biomarker to predict metastasis as well as a potential cancer therapeutic target. PMID- 26857389 TI - Dietary protein intake is associated with better physical function and muscle strength among elderly women. AB - Dietary protein intake might be beneficial to physical function (PF) in the elderly. We examined the cross-sectional and prospective associations of protein intake of g/kg body weight (BW), fat mass (FM) and lean mass (LM) with PF in 554 women aged 65.3-71.6 years belonging to the Osteoporosis Risk Factor and Prevention Fracture Prevention Study. Participants filled a questionnaire on lifestyle factors and 3-d food record in 2002. Body composition was measured by dual-energy X-ray absorptiometry, and PF measures were performed at baseline and at 3-year follow-up. Sarcopaenia was defined using European Working Group on Sarcopenia in Older People criteria. At the baseline, women with higher protein intake (>= 1.2 g/kg BW) had better performance in hand-grip strength/body mass (GS/BM) (P=0.001), knee extension/BM (P=0.003), one-leg stance (P=0.047), chair rise (P=0.043), squat (P=0.019), squat to the ground (P=0.001), faster walking speed for 10 m (P=0.005) and higher short physical performance battery score (P=0.004) compared with those with moderate and lower intakes (0.81-1.19 and <= 0.8 g/kg BW, respectively). In follow-up results, higher protein intake was associated with less decline in GS/BM, one-leg stance and tandem walk for 6 m over 3 years. Overall, results were no longer significant after controlling for FM. Associations were detected between protein intake and PF in non-sarcopaenic women but not in sarcopaenic women, except for change of GS (P=0.037). Further, FM but not LM was negatively associated with PF measures (P<0.050). This study suggests that higher protein intake and lower FM might be positively associated with PF in elderly women. PMID- 26857390 TI - Fertilizer regime impacts on abundance and diversity of soil fauna across a poplar plantation chronosequence in coastal Eastern China. AB - Soil fauna are critical for ecosystem function and sensitive to the changes of soil fertility. The effects of fertilization on soil fauna communities, however, remain poorly understood. We examined the effects of fertilization form and quantity on the abundance, diversity and composition of soil fauna across an age sequence of poplar plantations (i.e., 4-, 9- and 20-yr-old) in the coastal region of eastern China. We found that the effects of fertilization on faunal abundance, diversity, and composition differed among stand ages. Organic fertilizers increased the total abundance of soil fauna, whereas low level inorganic fertilizers imparted increases only in the 4- and 9-yr-old stands. The number of faunal groups did not change with fertilization, but Shannon's and Margalef diversity indices increased under low level organic fertilization, and decreased under inorganic fertilization in the 9- and 20-yr-old stands. Community composition of soil fauna differed strongly with fertilization and stand age. The changes in soil fauna were strongly associated with the changes in microbial biomass carbon, dissolved organic carbon and nitrogen, and available phosphorus and potassium. Our findings suggest that the responses of soil fauna to fertilization may be mediated through the fertilization effects on soil nutrient availability. PMID- 26857393 TI - Genomic Testing for Gemcitabine-Based Treatment of Pancreatic Cancer. PMID- 26857394 TI - Extensive Variation in the Mutation Rate Between and Within Human Genes Associated with Mendelian Disease. AB - We have investigated whether the mutation rate varies between genes and sites using de novo mutations (DNMs) from three genes associated with Mendelian diseases (RB1, NF1, and MECP2). We show that the relative frequency of mutations at CpG dinucleotides relative to non-CpG sites varies between genes and relative to the genomic average. In particular we show that the rate of transition mutation at CpG sites relative to the rate of non-CpG transversion is substantially higher in our disease genes than amongst DNMs in general; the rate of CpG transition can be several hundred-fold greater than the rate of non-CpG transversion. We also show that the mutation rate varies significantly between sites of a particular mutational type, such as non-CpG transversion, within a gene. We estimate that for all categories of sites, except CpG transitions, there is at least a 30-fold difference in the mutation rate between the 10% of sites with the highest and lowest mutation rates. However, our best estimate is that the mutation rate varies by several hundred-fold variation. We suggest that the presence of hypermutable sites may be one reason certain genes are associated with disease. PMID- 26857391 TI - Oral Palmitoylethanolamide Treatment Is Associated with Reduced Cutaneous Adverse Effects of Interferon-beta1a and Circulating Proinflammatory Cytokines in Relapsing-Remitting Multiple Sclerosis. AB - Palmitoylethanolamide (PEA) is an endogenous lipid mediator known to reduce pain and inflammation. However, only limited clinical studies have evaluated the effects of PEA in neuroinflammatory and neurodegenerative diseases. Multiple sclerosis (MS) is a chronic autoimmune and inflammatory disease of the central nervous system. Although subcutaneous administration of interferon (IFN)-beta1a is approved as first-line therapy for the treatment of relapsing-remitting MS (RR MS), its commonly reported adverse events (AEs) such as pain, myalgia, and erythema at the injection site, deeply affect the quality of life (QoL) of patients with MS. In this randomized, double-blind, placebo-controlled study, we tested the effect of ultramicronized PEA (um-PEA) added to IFN-beta1a in the treatment of clinically defined RR-MS. The primary objectives were to estimate whether, with um-PEA treatment, patients with MS perceived an improvement in pain and a decrease of the erythema width at the IFN-beta1a injection site in addition to an improvement in their QoL. The secondary objectives were to evaluate the effects of um-PEA on circulating interferon-gamma, tumor necrosis factor-alpha, and interleukin-17 serum levels, N-acylethanolamine plasma levels, Expanded Disability Status Scale (EDSS) progression, and safety and tolerability after 1 year of treatment. Patients with MS receiving um-PEA perceived an improvement in pain sensation without a reduction of the erythema at the injection site. A significant improvement in QoL was observed. No significant difference was reported in EDSS score, and um-PEA was well tolerated. We found a significant increase of palmitoylethanolamide, anandamide and oleoylethanolamide plasma levels, and a significant reduction of interferon-gamma, tumor necrosis factor alpha, and interleukin-17 serum profile compared with the placebo group. Our results suggest that um-PEA may be considered as an appropriate add-on therapy for the treatment of IFN-beta1a-related adverse effects in RR-MS. PMID- 26857392 TI - Relevance of Sp Binding Site Polymorphism in WWOX for Treatment Outcome in Pancreatic Cancer. AB - BACKGROUND: A genome-wide association study (GWAS) suggested inherited genetic single-nucleotide polymorphisms (SNPs) affecting overall survival (OS) in advanced pancreatic cancer. To identify robust clinical biomarkers, we tested the strongest reported candidate loci in an independent patient cohort, assessed cellular drug sensitivity, and evaluated molecular effects. METHODS: This study comprised 381 patients with histologically verified pancreatic ductal adenocarcinoma treated with gemcitabine-based chemotherapy. The primary outcome was the relationship between germline polymorphisms and OS. Functional assays addressed pharmacological dose-response effects in lymphoblastoid cell lines (LCLs) and pancreatic cancer cell lines (including upon RNAi), gene expression analyses, and allele-specific transcription factor binding. All statistical tests were two-sided. RESULTS: The A allele (26% in Caucasians) at SNP rs11644322 in the putative tumor suppressor gene WWOX conferred worse prognosis. Median OS was 14 months (95% confidence interval [CI] = 12 to 15 months), 13 months (95% CI = 11 to 15 months), and nine months (95% CI = 7 to 12 months) for the GG, GA, and AA genotypes, respectively (P trend < .001 for trend in univariate log-rank assuming a codominant mode of inheritance; advanced disease subgroup P trend < .001). Mean OS was 25 months (95% CI = 21 to 29 months), 19 months (95% CI = 15 to 22 months), and 13 months (95% CI = 10 to 16 months), respectively. This effect held true after adjustment for age, performance status according to Eastern Cooperative Oncology Group classification, TNM, grading, and resection status and was comparable with the strongest established prognostic factors in multivariable analysis. Consistently, reduced responsiveness to gemcitabine, but not 5-fluorouracil, along with lower WWOX expression was demonstrated in LCLs harboring the AA genotype. Likewise, RNAi-mediated WWOX knockdown in pancreatic cancer cells confirmed differential cytostatic drug sensitivity. In electrophoretic mobility shift assays, the A allele exhibited weaker binding of Sp family members Sp1/Sp3. CONCLUSIONS: WWOX rs11644322 represents a major predictive factor in gemcitabine-treated pancreatic cancer. Decreased WWOX expression may interfere with gemcitabine sensitivity, and allele-specific binding at rs11644332 might be a causative molecular mechanism behind the observed clinical associations. PMID- 26857395 TI - Legionellosis in Transplantation. AB - Legionella species are emerging opportunistic pathogens in hematopoietic stem cell and solid organ transplant recipients, associated with significant morbidity and mortality. The clinical and radiological features of Legionella infections can mimic other opportunistic pathogens in these profoundly immunocompromised patients. Diagnosis in transplant patients is challenging as non-pneumophila Legionella infections, for which these patients are at risk, cannot be identified using the urinary antigen test. Changes in management of transplant recipients and changes in Legionella epidemiology suggest that the number of transplant patients potentially exposed to Legionella spp. may be on the rise. Yet, evidence based, transplant-specific guidelines for managing and preventing Legionella infections are not currently available. In this article, we review the epidemiology, clinical features, diagnostic challenges, treatment options, and preventive strategies of Legionella infections in these high-risk patient populations. PMID- 26857397 TI - Preconditioning of Nonlinear Mixed Effects Models for Stabilisation of Variance Covariance Matrix Computations. AB - As the importance of pharmacometric analysis increases, more and more complex mathematical models are introduced and computational error resulting from computational instability starts to become a bottleneck in the analysis. We propose a preconditioning method for non-linear mixed effects models used in pharmacometric analyses to stabilise the computation of the variance-covariance matrix. Roughly speaking, the method reparameterises the model with a linear combination of the original model parameters so that the Hessian matrix of the likelihood of the reparameterised model becomes close to an identity matrix. This approach will reduce the influence of computational error, for example rounding error, to the final computational result. We present numerical experiments demonstrating that the stabilisation of the computation using the proposed method can recover failed variance-covariance matrix computations, and reveal non identifiability of the model parameters. PMID- 26857396 TI - An Integrated Strategy for Implementation of Dried Blood Spots in Clinical Development Programs. AB - Dried blood spot (DBS) sample collection has gained increased interest across the pharmaceutical industry as a potential alternative to plasma for pharmacokinetic (PK) evaluations. However, regulatory guidelines and examples of late-stage clinical trial applications in the literature are lacking. This paper communicates Merck's strategy for the implementation of DBS exemplified by experience on a late-stage program (MK-8931). In this program, DBS was proposed as the sole matrix for phase 3 studies to decrease logistical burden in an aging target patient population (Alzheimer's disease). In vitro and bioanalytical tests demonstrated initial method feasibility and suitability for further evaluations in the clinic. An in vivo dataset was developed initially in healthy subjects (phase 1 study) and then in patients (phase 2/3 study) to establish a quantitative relationship between the blood and plasma concentrations (bridging dataset) using descriptive and population PK analyses. This allowed for PK conclusions to be seamlessly drawn across the clinical program without impact from the choice of matrix. This integrated information package (in vitro, bioanalytical and clinical) was presented to major regulatory agencies (FDA and EMA) for regulatory input. Based on this package, regulatory concurrence was gained on accepting DBS as the sole matrix in late-stage clinical trials. PMID- 26857398 TI - The peripheral nerve involvement in Parkinson Disease: A multifaceted phenomenon. AB - In the last decade the possible relationship between Parkinson's disease (PD) and peripheral neuropathy (PN) has received increasing attention. Given that PN is quite common in Parkinson's disease, much controversy has arisen on whether it is part of the neurogenerative process itself - actually one of the possible causes or a complication of levodopa administration. In this article we will discuss the different hypotheses, as well as our perspective on these open issues. PMID- 26857400 TI - Questionnaire identifying management practices surrounding calving on spring calving dairy farms and their associations with herd size and herd expansion. AB - Healthy calves are fundamental to any profitable dairy enterprise. Research to date, has focused on year-round calving systems which experience many different challenges compared to spring-calving systems. The objective of the present study was to determine the on-farm dry cow, calving, and colostrum management practices of spring-calving dairy production systems, and quantify their associations with herd size and herd expansion status (i.e. expanding or not expanding). Information on these management practices was available from a survey of 262 Irish spring-calving dairy farmers, representative of the Irish national population. Herd expansion in the 2 years before, and the year that the survey was conducted was not associated with any of the management practices investigated. Fifty-three percent of respondents had an average calving season length of 10 to14 weeks with 35% of herds having a longer calving season. Previous research in cattle has documented that both colostrum source and feeding management are associated with the transmission of infectious disease from cow to calf. In the present study 60% of respondents fed calves colostrum from their own dam; however, 66% of those respondents allowed the calf to suckle the dam, 23% of survey respondents fed calves pooled colostrum. Larger herds were more likely (P<0.01) to use pooled colostrum supplies, while smaller herds were more likely (P<0.05) to allow the calf to suckle the dam. The majority (86%) of respondents had stored supplies of colostrum; average-sized herds had the greatest likelihood of storing colostrum (P<0.05), compared to other herd sizes; larger sized herds had a lesser likelihood (P<0.05) of storing colostrum in a freezer, compared to other herd sizes. Although freezing colostrum was the most common method used to store colostrum (54% of respondents), 17% of respondents stored colostrum at room temperature, 29% of which stored it at room temperature for greater than 4 days. The results from the present study indicate that a particular focus needs to be placed on calving and colostrum management because this study has highlighted a number of areas which are below international standards, and may have repercussions for calf health. Furthermore, management practices on larger farms could be improved and, as these represent the future of dairy farming, a focus needs to be placed on them. Expanding herds are not a particular concern as herd expansion, independent of herd size, does not seem to be associated with calving and colostrum management practices on Irish spring-calving dairy herds. PMID- 26857401 TI - Mitochondrial DNA variation of Protosalanx hyalocranius in the Huaihe River. PMID- 26857399 TI - Cortical and motor responses to acute forced exercise in Parkinson's disease. AB - INTRODUCTION: Studies in animal models of Parkinson's disease (PD) have suggested that the rate of exercise performance is important in treatment efficacy and neuroprotection. In humans with PD, lower-extremity forced-exercise (FE) produced global improvements in motor symptoms based on clinical ratings and biomechanical measures of upper extremity function. METHODS: fMRI was used to compare the underlying changes in brain activity in PD patients following the administration of anti-parkinsonian medication and following a session of FE. RESULTS: Nine individuals with PD completed fMRI scans under each condition: off anti-PD medication, on anti-PD medication, and off medication + FE. Unified Parkinson's Disease Rating Motor Scale scores improved by 50% in the FE condition compared to the off-medication condition. The pattern of fMRI activation after FE was similar to that seen with anti-PD medication. Direct comparison of the fMRI activation patterns showed high correlation between FE and anti-PD medication. CONCLUSION: These findings suggest that medication and FE likely utilize the same pathways to produce symptomatic relief in individuals with PD. PMID- 26857402 TI - Mitochondrial Cristae: Where Beauty Meets Functionality. AB - Mitochondrial cristae are dynamic bioenergetic compartments whose shape changes under different physiological conditions. Recent discoveries have unveiled the relation between cristae shape and oxidative phosphorylation (OXPHOS) function, suggesting that membrane morphology modulates the organization and function of the OXPHOS system, with a direct impact on cellular metabolism. As a corollary, cristae-shaping proteins have emerged as potential modulators of mitochondrial bioenergetics, a concept confirmed by genetic experiments in mouse models of respiratory chain deficiency. Here, we review our knowledge of mitochondrial ultrastructural organization and how it impacts mitochondrial metabolism. PMID- 26857403 TI - Romantic Relationship Patterns from Adolescence to Emerging Adulthood: Associations with Family and Peer Experiences in Early Adolescence. AB - The present study identifies and describes romantic relationship patterns from adolescence to adulthood and examines their associations with family and peer experiences in early adolescence. In a 13-year longitudinal study, 281 youth (58 % girls) identified all their romantic partners each year from the ages of 16-24. Dimensions of family relationships (family cohesion, parent-child conflict) and peer relationships (peer likeability, social withdrawal, close friendships, other sex friendships) were assessed at age 12. Latent class analyses brought out five distinct romantic relationship patterns and significant associations were found with family and peer relationships in early adolescence. These five romantic relationship patterns appeared to follow a continuum of romantic involvement, with romantic relationship patterns situated a both ends of this continuum (later involvement pattern and intense involvement pattern) being associated with more interpersonal experiences in early adolescence. PMID- 26857404 TI - Vaccination Against Seasonal or Pandemic Influenza in Emergency Medical Services. AB - INTRODUCTION: Influenza is a major concern for Emergency Medical Services (EMS); EMS workers' (EMS-Ws) vaccination rates remain low despite promotion. Determinants of vaccination for seasonal influenza (SI) or pandemic influenza (PI) are unknown in this setting. HYPOTHESIS: The influence of the H1N1 pandemic on EMS-W vaccination rates, differences between SI and PI vaccination rates, and the vaccination determinants were investigated. METHODS: A survey was conducted in 2011 involving 65 Swiss EMS-Ws. Socio-professional data, self-declared SI/PI vaccination status, and motives for vaccine refusal or acceptation were collected. RESULTS: Response rate was 95%. The EMS-Ws were predominantly male (n=45; 73%), in good health (87%), with a mean age of 36 (SD=7.7) years. Seventy four percent had more than six years of work experience. Self-declared vaccination rates were 40% for both SI and PI (PI+/SI+), 19% for PI only (PI+/SI ), 1.6% for SI only (PI-/SI+), and 39% were not vaccinated against either (PI-/SI ). Women's vaccination rates specifically were lower in all categories but the difference was not statistically significant. During the previous three years, 92% of PI+/SI+ EMS-Ws received at least one SI vaccination; it was 8.3% in the case of PI-/SI- (P=.001) and 25% for PI+/SI- (P=.001). During the pandemic, SI vaccination rate increased from 26% during the preceding year to 42% (P=.001). Thirty percent of the PI+/SI+ EMS-Ws declared that they would not get vaccination next year, while this proportion was null for the PI-/SI- and PI+/SI- groups. Altruism and discomfort induced by the surgical mask required were the main motivations to get vaccinated against PI. Factors limiting PI or SI vaccination included the option to wear a mask, avoidance of medication, fear of adverse effects, and concerns about safety and effectiveness. CONCLUSION: Average vaccination rate in this study's EMS-Ws was below recommended values, particularly for women. Previous vaccination status was a significant determinant of PI and future vaccinations. The new mask policy seemed to play a dual role, and its net impact is probably limited. This population could be divided in three groups: favorable to all vaccinations; against all, even in a pandemic context; and ambivalent with a "pandemic effect." These results suggest a consistent vaccination pattern, only altered by exceptional circumstances. PMID- 26857405 TI - An Ultrasensitive Light-up Cu(2+) Biosensor Using a New DNAzyme Cleaving a Phosphorothioate-Modified Substrate. AB - Cu(2+) is a very important metal ion in biology, environmental science, and industry. Developing biosensors for Cu(2+) is a key topic in analytical chemistry. DNAzyme-based sensors are highly attractive for their excellent sensitivity, stability, and programmability. In the past decade, a few Cu(2+) biosensors were reported using DNAzymes with DNA cleavage or DNA ligation activity. However, they require unstable ascorbate or imidazole activation. So far, no RNA-cleaving DNAzymes specific for Cu(2+) are known. In this work, a phosphorothioate (PS) RNA-containing library was used for in vitro selection, and a few new Cu(2+)-specific RNA-cleaving DNAzymes were isolated. Among them, a DNAzyme named PSCu10 was studied further. It has only eight nucleotides in the enzyme loop with a cleavage rate of 0.1 min(-1) in the presence of 1 MUM Cu(2+) at pH 6.0 (its optimal pH). Between the two diastereomers of the PS RNA chiral center, the R(p) isomer is 37 times more active than the S(p) one. Among the other divalent metal ions, only Hg(2+) can cleave the substrate due to its extremely high thiophilicity. A catalytic beacon sensor was designed with a detection limit of 1.6 nM Cu(2+) and extremely high selectivity. PSCu10 is specific for Cu(2+), and it has no cleavage in the presence of ascorbate, which reduces Cu(2+) to Cu(+). PMID- 26857406 TI - [Not Available]. PMID- 26857407 TI - [Not Available]. PMID- 26857408 TI - [Not Available]. PMID- 26857409 TI - [Hyperhidrosis is a silent handicap]. AB - Hyperhidrosis affects 2.8% of the population and has severe negative influence on life quality. The disease is represented in many specialties but can unfortunately be incorrectly treated or not treated at all. Primary hyperhidrosis is the most common form. Secondary hyperhidrosis is most often excluded by a few anamnestic data. Botulinum toxin and anticholinergics are adequate treatment options when aluminium chloride is insufficient. This article describes the disease from the physician's as well as the patient's perspective. Furthermore, examination procedures and treatment procedures are presented. PMID- 26857410 TI - [Body position dependable nerve root compression in a patient with leg pain in standing position]. AB - Six months after L5 hemilaminectomy and discectomy a patient experienced diffuse radiating symptoms to the right leg, especially in the standing position. Conventional supine magnetic resonance imaging (MRI) showed some scar tissue in the L5 spinal recess but no signs of nerve root compression to neurogenic claudication. Subsequently, an MRI with the patient in standing position displayed lateral recess stenosis and nerve root compression. This supports the notion that spinal stenosis should be regarded as a dynamic phenomenon also in the diagnostic workup setting. PMID- 26857411 TI - [Positive psychiatry]. AB - Positive psychiatry (PP) is a field within psychiatry with a particular focus on promoting well-being in people who already have or are at high risk of developing mental or physical illness. PP should be considered a supplement to trad-tional psychiatry and a call for therapists in psychiatry to focus on the person as a whole rather than just as a patient. PP is in line with current national and international health policy focus on promoting positive mental health. PMID- 26857412 TI - [Dermatitis artefacta]. AB - Dermatitis artefacta is a self-inflicted skin disease with a multifactorial aetiology. The condition can be a symptom of an underlying psychiatric condition or a sign of psycho-social stressors. This paper gives an updated view on dermatitis artefacta. The majority of the patients have some form of psychiatric co-morbidity including depression and anxiety. Many have experienced negative life events such as diseases or deaths. Personality disorders were reported in only two studies. Treatment options besides the acute treatment of the skin were psychotherapy and psychotropic drugs. PMID- 26857413 TI - Transcranial magnetic stimulation (TMS) coupled with electroencephalography (EEG): Biomarker of the future. AB - INTRODUCTION: In recent years, a number of novel brain-stimulation techniques have been developed (such as TMS-EEG, TMS-fMRI and TMS-NIRS), yet they remain underutilized in the field of epilepsy. Accumulating evidence suggests that transcranial magnetic stimulation (TMS) combined with electroencephalography (TMS EEG) is a highly relevant technique for exploration of the pathophysiology of human epilepsies as well as a promising biomarker with diagnostic and prognostic potential. RESULTS: In genetic generalized epilepsies, TMS-EEG has provided pathophysiological insight by revealing quasi-stable, covert states of excitability, a subclass of which is associated with the generation of TMS induced epileptiform discharges (EDs). In focal epilepsy, TMS-induced EDs were successfully employed to identify the epileptogenic zone. In addition, TMS trains applied during focal EDs can terminate them, and appear to restore the effective connectivity of the brain network significantly altered by EDs. This abortive effect of TMS on EDs may possibly serve as a biomarker of response to invasive neuromodulatory techniques. CONCLUSION: TMS-EEG-based stimulation paradigms can provide insight into the mechanisms underlying human epilepsies and, thus, warrant further study as diagnostic and prognostic biomarkers. PMID- 26857414 TI - A hydrophilic matrix approach for controlled vaginal drug delivery. PMID- 26857415 TI - Early differential diagnosis between Alzheimer's disease and dementia with Lewy bodies: Comparison between (18)F-FDG PET and (123)I-IMP SPECT. AB - Both (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and (123)I iodoamphetamine (IMP) single-photon emission computed tomography (SPECT) have been used for the differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Less information is available, however, regarding the differential diagnosis of mild cognitive impairment (MCI) due to AD and MCI due to DLB. We examined nine AD patients (AD group), nine DLB patients (DLB group), eight MCI due to AD patients (MCI-AD group), and nine MCI due to DLB patients (MCI-DLB group) with FDG PET and IMP SPECT using a well-characterized normal database and a stereotactic extraction estimation method. In the AD and DLB groups, receiver operating characteristic (ROC) analysis in the occipital regions showed significant accuracy of both FDG PET and IMP SPECT for the differential diagnosis. In the MCI-AD and MCI-DLB groups, ROC analysis showed significant accuracy of only FDG PET for the differential diagnosis. Both FDG PET and IMP SPECT would be useful for the differential diagnosis between AD and DLB. For the differential diagnosis of MCI-AD versus MCI-DLB, FDG PET would be more useful than IMP SPECT. PMID- 26857416 TI - A Novel Technique for the Intraoperative Identification of Biliary Drainage Areas in the Liver after Hepatobiliary Resection for Perihilar Cholangiocarcinoma. PMID- 26857417 TI - Deciphering the fundamental mechanisms of atrial fibrillation: a quest for over a century. PMID- 26857418 TI - Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways. AB - AIMS: The adult mammalian heart has poor regenerative capacity. In contrast, the zebrafish heart retains a robust capacity for regeneration into adulthood. These distinct responses are consequences of a differential utilization of evolutionary conserved gene regulatory networks in the damaged heart. To systematically identify miRNA-dependent networks controlling cardiac repair following injury, we performed comparative gene and miRNA profiling of the cardiac transcriptome in adult mice and zebrafish. METHODS AND RESULTS: Using an integrated approach, we show that 45 miRNA-dependent networks, involved in critical biological pathways, are differentially modulated in the injured zebrafish vs. mouse hearts. We study, more particularly, the miR-26a-dependent response. Therefore, miR-26a is down regulated in the fish heart after injury, whereas its expression remains constant in the mouse heart. Targets of miR-26a involve activators of the cell cycle and Ezh2, a component of the polycomb repressive complex 2 (PRC2). Importantly, PRC2 exerts repressive functions on negative regulators of the cell cycle. In cultured neonatal cardiomyocytes, inhibition of miR-26a stimulates, therefore, cardiomyocyte proliferation. Accordingly, miR-26a knockdown prolongs the proliferative window of cardiomyocytes in the post-natal mouse heart. CONCLUSIONS: This novel strategy identifies a series of miRNAs and associated pathways, in particular miR-26a, which represent attractive therapeutic targets for inducing repair in the injured heart. PMID- 26857419 TI - Circulating 'lncRNA OTTHUMT00000387022' from monocytes as a novel biomarker for coronary artery disease. AB - AIMS: Long non-coding RNAs (lncRNAs) have been found to be involved in the pathogenesis of coronary artery disease (CAD). However, it remains to be established whether or not circulating lncRNAs can serve as biomarkers of CAD. METHODS AND RESULTS: Using a microarray-based lncRNA expression profiling, we found 86 lncRNAs that were differentially expressed in circulating peripheral blood monocytes and plasma from 15 CAD patients and 15 control subjects. After choosing a consistent criterion (average normalized intensity >=7 with significance <0.005) and confirmed by quantitative PCR, only three lncRNAs (CoroMarker, BAT5, and IL21R-AS1) remained as candidate CAD biomarkers. Using the analysis of area under the curve (AUC) of the receiver-operating characteristic in another pilot group and another larger cohort, CoroMarker was found to be the best candidate biomarker for CAD with an AUC of 0.920 and 95% confidence interval of 0.892-0.947. CoroMarker was independent from known CAD risk factors and other cardiovascular diseases. In a prospective study, we found that the sensitivity and specificity of CoroMarker were 76 and 92.5%, respectively. Functional enrichment analysis showed CoroMarker to be clustered with genes positively associated with signal transduction, transmembrane transport, synaptic transmission, and innate immunity and negatively associated with inflammation. These findings were validated in THP-1 cells; CoroMarker siRNA treatment decreased the concentrations of proinflammatory cytokines [interleukin (IL) 1beta, IL-6, and tumour necrosis factor alpha] in the culture medium. CONCLUSION: The present study suggests that CoroMarker is a novel and specific biomarker of CAD. PMID- 26857420 TI - Proteomic analysis of a compatible interaction between sugarcane and Sporisorium scitamineum. AB - Smut caused by Sporisorium scitamineum is one of the important diseases of sugarcane with global significance. Despite the intriguing nature of sugarcane, S. scitamineum interaction, several pertinent aspects remain unexplored. This study investigates the proteome level alterations occurring in the meristem of a S. scitamineum infected susceptible sugarcane cultivar at whip emergence stage. Differentially abundant proteins were identified by 2DE coupled with MALDI TOF/TOF-MS. Comprehensively, 53 sugarcane proteins identified were related to defence, stress, metabolism, protein folding, energy, and cell division; in addition, a putative effector of S. scitamineum, chorismate mutase, was identified. Transcript expression vis-a-vis the activity of phenylalanine ammonia lyase was relatively higher in the infected meristem. Abundance of seven candidate proteins in 2D gel profiles was in correlation with its corresponding transcript expression levels as validated by qRT-PCR. Furthermore, this study has opened up new perspectives on the interaction between sugarcane and S. scitamineum. PMID- 26857421 TI - Ultra low-dose chest ct with iterative reconstructions as an alternative to conventional chest x-ray prior to heart surgery (CRICKET study): Rationale and design of a multicenter randomized trial. AB - BACKGROUND: Stroke after cardiac surgery is a severe complication with a persistently high incidence of 1.4 - 9.7%. Postoperative strokes are mainly embolic and can be provoked by manipulation and clamping of the aorta during cardiac surgery, resulting in the mobilization of atherothrombotic material and calcifications from the aortic wall. Computed tomography (CT) can offer preoperative visualization of aortic calcifications with low radiation exposure. We hypothesize that preoperative knowledge regarding the location and extent of aortic calcifications can be used to optimize surgical strategy and decrease postoperative stroke rate. METHODS/DESIGN: The CRICKET study (ultra low-dose chest CT with iterative reconstructions as an alternative to conventional chest x ray prior to heart surgery) is a prospective multicenter randomized clinical trial to evaluate whether non-contrast chest CT before cardiac surgery can decrease postoperative stroke rate by optimizing surgical strategy. Patients scheduled to undergo cardiac surgery aged 18 years and older are eligible for inclusion. Exclusion criteria are pregnancy, a chest/cardiac CT in the past three months, emergency surgery, concomitant or prior participation in a study with ionizing radiation and unwillingness to be informed about incidental findings. Subjects (n = 1.724) are randomized between routine care, including a chest x ray, or routine care with an additional low dose chest CT. The primary objective is to investigate whether the postoperative in-hospital stroke rate is reduced in the CT arm compared to the routine care arm of the randomized trial. The secondary outcome measures are altered surgical approach based on CT findings and cost-effectiveness. PMID- 26857422 TI - Absence of coronary sinus tributaries in ischemic cardiomyopathy: An insight from multidetector computed tomography cardiac venographic study. AB - OBJECTIVE: Cardiac resynchronization therapy (CRT) is an important therapeutic strategy in heart failure. However, there is a high incidence of lead implantation failure and suboptimal response, particularly in ischemic cardiomyopathy. This failure rate may partly be secondary to lack of suitable coronary sinus branches for lead implantation. We sought to assess the presence of coronary sinus (CS) tributaries in patients with ischemic and non-ischemic cardiomyopathy. MATERIALS AND METHODS: Multidetector computed tomography (MDCT) was performed in 100 patients: 25 coronary artery bypass graft (CABG) patients with impaired left ventricular ejection fraction (LVEF), 25 CABG patients with preserved LVEF, 25 patients with non-ischemic cardiomyopathy, and 25 controls. The presence of the CS and its tributaries, including the posterior interventricular vein (PIV), posterolateral vein (PLV), left marginal vein (LMV), and the anterior interventricular vein (AIV) was assessed. RESULTS: The CS, PIV, and AIV were demonstrated in all patients, whereas presence of a PLV and LMV was identified in 68% and 48% of CABG patients with impaired LVEF, 96% and 68% of CABG patients with preserved LVEF, 92% and 80% of patients with non-ischemic cardiomyopathy, and 100% and 80% of controls (p = 0.001 and 0.046 for PLV and LMV, respectively). CONCLUSIONS: This is the first report to demonstrate that the posterolateral vein and left middle vein, branches of the coronary sinus, are detectable in a significantly smaller number of CABG patients with impaired LVEF compared to controls, CABG with preserved LVEF, and non-ischemic cardiomyopathy. The absence of CS tributary veins in ischemic cardiomyopathy potentially hinders proper lead implantation and results in suboptimal CRT response. PMID- 26857423 TI - Characterization of the Human Risk of Salmonellosis Related to Consumption of Pork Products in Different E.U. Countries Based on a QMRA. AB - In response to the European Food Safety Authority's wish to assess the reduction of human cases of salmonellosis by implementing control measures at different points in the farm-to-consumption chain for pork products, a quantitative microbiological risk assessment (QMRA) was developed. The model simulated the occurrence of Salmonella from the farm to consumption of pork cuts, minced meat, and fermented ready-to-eat sausage, respectively, and a dose-response model was used to estimate the probability of illness at consumption. The QMRA has a generic structure with a defined set of variables, whose values are changed according to the E.U. member state (MS) of interest. In this article we demonstrate the use of the QMRA in four MSs, representing different types of countries. The predicted probability of illness from the QMRA was between 1 in 100,000 and 1 in 10 million per serving across all three product types. Fermented ready-to-eat sausage imposed the highest probability of illness per serving in all countries, whereas the risks per serving of minced meat and pork chops were similar within each MS. For each of the products, the risk varied by a factor of 100 between the four MSs. The influence of lack of information for different variables was assessed by rerunning the model with alternative, more extreme, values. Out of the large number of uncertain variables, only a few of them have a strong influence on the probability of illness, in particular those describing the preparation at home and consumption. PMID- 26857424 TI - Evaluation of Quality of Life, Functioning, Disability, and Work/School Productivity Following Treatment with an Extended-Release Hydrocodone Tablet Formulated with Abuse-Deterrence Technology: A 12-month Open-label Study in Patients with Chronic Pain. AB - BACKGROUND: This phase 3 study evaluated quality of life, functioning, and productivity after treatment with extended-release (ER) hydrocodone formulated with CIMA(r) Abuse-Deterrence Technology platform. METHODS: Patients with chronic pain were rolled over from a 12-week placebo-controlled hydrocodone ER study or were newly enrolled. Hydrocodone ER doses were titrated (15 to 90 mg every 12 hours) to an analgesic dose, and patients received up to 52 weeks of open-label treatment. Assessments included Clinician Assessment of Patient Function (CAPF), Patient Assessment of Function (PAF), Brief Pain Inventory-Short Form (BPI-SF), 36-item Short-Form Health Survey (SF-36), Sheehan Disability Scale (SDS), and World Health Organization Health and Work Performance Questionnaire-Short Form (HPQ-SF). RESULTS: Of 330 enrolled patients, 291 composed the full analysis population. By week 4, >= 50% of patients showed improvement from baseline in all 5 CAPF domains (general activities, walking, work/daily living, relationships, and enjoyment of life) and 6 of 7 PAF domains (work attendance, work performance, walking, exercise, socializing, and enjoying life). Mean decreases from baseline of 2 to 3 points were noted for BPI-SF pain interference questions from week 4 through endpoint. Mean improvements from baseline to endpoint in SF-36 subscales ranged from 3.3 to 22.3, and SDS scores improved from moderate (4.8 to 5.1) to mild (2.5 to 2.8) disruptions in work/school, social life, and family life. At endpoint, mean HPQ-SF absolute absenteeism scores decreased from 13.6 to 10.0 hours lost/month and absolute presenteeism scores improved from 67.0 to 77.1. CONCLUSIONS: Patients receiving hydrocodone ER showed early numeric improvements in functioning that continued throughout this 12-month study. PMID- 26857425 TI - [In vitro activity of ampicillin-ceftriaxone against Enterococcus faecalis isolates recovered from invasive infections]. AB - In vitro activity of the combination of ampicillin- ceftriaxone against 30 Enterococcus faecalis isolates recovered from invasive infections in patients admitted to Hospital de Clinicas Jose de San Martin in the city of Buenos Aires was assessed. Ampicillin- ceftriaxone synergies were determined by microdilution in Mueller-Hinton (MH) broth with and without subinhibitory concentrations of ceftriaxone. Synergy was detected in 22/30 isolates. A decrease in both minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was observed in 14/30 isolates, whereas in 6/30 isolates the decrease was observed in the MIC value and only in the MBC value in the 2 remaining isolates. The bactericidal activity of the combination showed to be higher at low concentrations of ampicillin (< 1 MUg/ml). We detected in vitro synergy using the ampicillin-ceftriaxone combination and thus, its efficacy was confirmed in the treatment of severe infections by E. faecalis. PMID- 26857426 TI - Successful achievement of sustained virological response to triple combination therapy containing simeprevir in two patients with chronic hepatitis C who had failed asunaprevir:Daclatasvir combination therapy. AB - Patients 1 and 2 were treatment-naive women who had genotype 1b chronic hepatitis C. Both had IL-28B genotype TT, and amino acid substitutions of core 70 and 91 were both wild type. Search for the presence of resistance-associated variants (RAV) in non-structural (NS)3 and NS5A regions confirmed wild-type D168 and L31, along with Y93H, in both patients. These patients participated in a Japanese phase III clinical study of asunaprevir and daclatasvir at the age of 52 and 67 years, respectively, and were treated with the combination regimen for 24 weeks. However, both experienced post-treatment relapse, and then treated with triple combination therapy with simeprevir, pegylated interferon (IFN) and ribavirin at the age of 53 and 68 years, respectively, and achieved sustained virological response. A search for RAV prior to simeprevir treatment identified multiple resistance including D168E, Y93H and L31V in both patients. It has been demonstrated that, in many cases, a treatment failure with a combination of asunaprevir and daclatasvir results in acquisition of RAV in NS3 and NS5A regions and that drug-resistant mutants, particularly those in the NS5A region, survive for a long time. In these cases, direct-acting antivirals targeted towards the NS5A region may have a limited efficacy. The present case report is based on an idea that a regimen containing IFN with simeprevir could be a therapeutic option particularly for those who are likely to be highly sensitive and tolerable to IFN. PMID- 26857427 TI - All-optical control of cardiac excitation: combined high-resolution optogenetic actuation and optical mapping. AB - Cardiac tissue is an excitable system that can support complex spatiotemporal dynamics, including instabilities (arrhythmias) with lethal consequences. While over the last two decades optical mapping of excitation (voltage and calcium dynamics) has facilitated the detailed characterization of such arrhythmia events, until recently, no precise tools existed to actively interrogate cardiac dynamics in space and time. In this work, we discuss the combined use of new methods for space- and time-resolved optogenetic actuation and simultaneous fast, high resolution optical imaging of cardiac excitation waves. First, the mechanisms, limitations and unique features of optically induced responses in cardiomyocytes are outlined. These include the ability to bidirectionally control the membrane potential using depolarizing and hyperpolarizing opsins; the ability to induce prolonged sustained voltage changes; and the ability to control refractoriness and the shape of the cardiac action potential. At the syncytial tissue level, we discuss optogenetically enabled experimentation on cell-cell coupling, alteration of conduction properties and termination of propagating waves by light. Specific attention is given to space- and time-resolved application of optical stimulation using dynamic light patterns to perturb ongoing activation and to probe electrophysiological properties at desired tissue locations. The combined use of optical methods to perturb and to observe the system can offer new tools for precise feedback control of cardiac electrical activity, not available previously with pharmacological and electrical stimulation. These new experimental tools for all-optical electrophysiology allow for a level of precise manipulation and quantification of cardiac dynamics comparable in robustness to the computational setting, and can provide new insights into pacemaking, arrhythmogenesis and suppression or cardioversion. PMID- 26857430 TI - Introduction to the Special Issue: Prospection difficulties in clinical populations. PMID- 26857428 TI - High-Pressure-Assisted Enzymatic Release of Peptides and Phenolics Increases Angiotensin Converting Enzyme I Inhibitory and Antioxidant Activities of Pinto Bean Hydrolysates. AB - Pinto bean protein concentrate was hydrolyzed by subtilisins at 0.1, 100, and 200 MPa and 50 degrees C for 15 min. Alcalase hydrolysis at 100 MPa led to higher ACE inhibition, reducing power, and free radical scavenging activity of hydrolysates. However, hydrolysate obtained by Savinase at 200 MPa showed the best ACE-inhibitory and radical scavenging activities. Proteolysis by Savinase at 200 MPa was considered the most effective treatment to increase small peptides (<3 kDa), flavonoids, total phenolic compounds, and oxygen radical absorbance capacity in hydrolysates. In this hydrolysate, small phaseolin fragments with reported ACE-inhibitory and antioxidant sequences were identified. Catechin, pelargonidin 3-glucoside, and ferulic acid were the main phenolic compounds. Hihg pressure-assisted hydrolysis of common bean protein concentrates would provide benefits in the production of functional hydrolysates providing higher functionality and added value to the resulting hydrolysate due to synergistic effects of bioactive peptides and soluble phenolics. PMID- 26857432 TI - Multiple Coronary Artery Aneurysms of the Right Coronary Artery in Neonate with Pulmonary Atresia with Intact Ventricular Septum. AB - Pulmonary atresia with intact ventricular septum (PA/IVS) with right ventricular dependent coronaries is a rare congenital cardiac anomaly. It has been associated with wide range of considerable anomalies including sinusoids, fistulae, coronary stenosis, or complete atresia. Coronary artery aneurysms in a neonate with PA/IVS have not been described. We report a case of neonate with pulmonary atresia with intact ventricular septum with giant coronary artery aneurysms. PMID- 26857429 TI - Effect of daily sildenafil on patients with absent nocturnal erections due to pelvic fracture urethral disruption: a single-centre experience. AB - Erectile dysfunction (ED) is a common sequel of pelvic fracture urethral disruption. Those patients with nocturnal erections may respond favourably to sildenafil; however, little is known about the response to sildenafil in patients with absent nocturnal erections. The aim was to evaluate the response to the treatment of sildenafil 50 mg taken once daily in the patients with absent nocturnal erections. From January 2008 to December 2011, a total of 28 patients with absent nocturnal erections were evaluated. We recorded nocturnal penile tumescence and rigidity with an erectometer. If nocturnal erections were absent for three nights, patients were administrated sildenafil 100 mg at bedtime and tested again at the fourth night. Penile duplex ultrasound with intracavernous injection was performed to define the cause of ED. All patients received a daily dose of sildenafil 50 mg for 12 weeks. Response to sildenafil treatment was defined as sustained erections allowing vaginal penetration and intercourse. Twenty-three (78%) patients completed the daily sildenafil treatment, and follow up was available. The nocturnal erections at the fourth night in 13 patients (46.4%) were improved. About 61.5% (8/13) reported effective response to daily sildenafil. The improvement of nocturnal erections induced by sildenafil taken at bedtime might predict the response to sildenafil taken daily. PMID- 26857433 TI - Transpulmonary thermodilution (PiCCO) measurements in children without cardiopulmonary dysfunction: large interindividual variation and conflicting reference values. AB - BACKGROUND: The PiCCO system, based on transpulmonary thermodilution, is one of the few tools available for continuous hemodynamic monitoring in children. However, published data for some of the derived variables reveal indexed values that seem questionable. AIMS: The aim of this study was to collect data from hemodynamically normal children and compare these to existing reference values. Furthermore, we sought to explore if indexing some of the variables differently could improve the clinical application of the obtained values. METHODS: This is a prospective observational study in a tertiary university hospital including 31 children without cardiopulmonary disease scheduled for major neurosurgery. Measurements were performed after induction of general anesthesia. RESULTS: Median age was 8 months. PiCCO-derived median Cardiac Index (CI) was 3.8 l . min( 1) . m(-2) (range 2.6-6.6), reference range 3.0-5.0, median Global End-Diastolic Volume Index (GEDVI) was 366 ml . m(-2) (range 269-685), reference range 680-800, whereas median Extravascular Lung Water Index (EVLWI) was 12 ml . kg(-1) (range 7 31), reference range 3-7. All measured variables had a high interindividual variation, especially in children weighing less than 15 kg. CONCLUSIONS: Values obtained by the PiCCO system in children have a wide range, and should therefore be interpreted with caution. Current reference values published for GEDVI and EVLWI are not applicable in children; the former is too high and the latter too low, and should not guide clinical practice. Indexing by other physiological indices may reduce this problem. Using current variables, we find GEDVI 280-590 ml . m(-2) and ELWI 7-27 ml . kg(-1) to be typical ranges for children. PMID- 26857434 TI - CASP11 statistics and the prediction center evaluation system. AB - We outline the role of the Protein Structure Prediction Center (predictioncenter.org) in conducting the CASP11 and CASP ROLL experiments, discuss the experiment statistics, and provide an overview of the present CASP infrastructure. The biggest changes compared to the previous CASPs are the implementation of the evaluation system incorporating practically all evaluation measures, statistical tests, and visualization tools historically used by the CASP assessors, the expansion of the infrastructure to incorporate new categories of contact-assisted and multimeric predictions, and the redesign of the assessors' web-workspace enabling assessments based on multiple measures for different group categories and target sets. Proteins 2016; 84(Suppl 1):15-19. (c) 2016 Wiley Periodicals, Inc. PMID- 26857435 TI - Mucormycete infection or colonisation: experience of an Australian tertiary referral centre. AB - Mucormycosis is associated with significant morbidity and mortality. We reviewed patients with mucormycete isolated at Alfred Health, Australia. A retrospective review of 66 patients with mucormycete(s) identified, between 1 April 2008 and 30 June 2014. Baseline demographic, microbiological, radiological, treatment/outcome data were recorded. Site of isolation was sinopulmonary in 77% and skin/soft tissue in 21%. A total of 32% of cases were proven-IFD, 12% probable-IFD and 56% were defined as no-IFD (or colonisation). Rhizopus spp. was identified in 48%. Comparing probable/proven-IFD with no-IFD/colonisation, more patients were postallogeneic stem cell transplantation (28% vs. 0%, P < 0.01) and were receiving immunosuppressive therapy (59% vs. 24%, P < 0.01) including prednisolone >20 mg daily (24% vs. 5%, P = 0.04). A total of 93% of patients with proven/probable IFD received treatment while 30% of no-IFD/colonisation were treated. A total of 72% of patients with proven/probable IFD and 92% of those with colonisation had no further mucormycete isolated. Thirty day mortality was higher in the proven/probable-IFD cohort (24%) compared with no-IFD/colonisation (3%) (P = 0.02). Mucormycosis remains uncommon, with 56% of cases not associated with clinical infection. Immunosuppressive therapy remains strongly associated with mucormycosis. Mortality remains high in those with proven/probable IFD. PMID- 26857436 TI - People-Technology-Ecosystem Integration: A Framework to Ensure Regional Interoperability for Safety, Sustainability, and Resilience of Interdependent Energy, Water, and Seafood Sources in the (Persian) Gulf. AB - OBJECTIVE: The aim of this study is to identify the interdependencies of human and organizational subsystems of multiple complex, safety-sensitive technological systems and their interoperability in the context of sustainability and resilience of an ecosystem. BACKGROUND: Recent technological disasters with severe environmental impact are attributed to human factors and safety culture causes. One of the most populous and environmentally sensitive regions in the world, the (Persian) Gulf, is on the confluence of an exponentially growing number of two industries--nuclear power and seawater desalination plants--that is changing its land- and seascape. METHOD: Building upon Rasmussen's model, a macrosystem integrative framework, based on the broader context of human factors, is developed, which can be considered in this context as a "meta-ergonomics" paradigm, for the analysis of interactions, design of interoperability, and integration of decisions of major actors whose actions can affect safety and sustainability of the focused industries during routine and nonroutine (emergency) operations. CONCLUSION: Based on the emerging realities in the Gulf region, it is concluded that without such systematic approach toward addressing the interdependencies of water and energy sources, sustainability will be only a short-lived dream and prosperity will be a disappearing mirage for millions of people in the region. APPLICATION: This multilayered framework for the integration of people, technology, and ecosystem--which has been applied to the (Persian) Gulf--offers a viable and vital approach to the design and operation of large-scale complex systems wherever the nexus of water, energy, and food sources are concerned, such as the Black Sea. PMID- 26857437 TI - Heterogeneous genome divergence, differential introgression, and the origin and structure of hybrid zones. AB - Hybrid zones have been promoted as windows on the evolutionary process and as laboratories for studying divergence and speciation. Patterns of divergence between hybridizing species can now be characterized on a genomewide scale, and recent genome scans have focused on the presence of 'islands' of divergence. Patterns of heterogeneous genomic divergence may reflect differential introgression following secondary contact and provide insights into which genome regions contribute to local adaptation, hybrid unfitness and positive assortative mating. However, heterogeneous genome divergence can also arise in the absence of any gene flow, as a result of variation in selection and recombination across the genome. We suggest that to understand hybrid zone origins and dynamics, it is essential to distinguish between genome regions that are divergent between pure parental populations and regions that show restricted introgression where these populations interact in hybrid zones. The latter, more so than the former, reveal the likely genetic architecture of reproductive isolation. Mosaic hybrid zones, because of their complex structure and multiple contacts, are particularly good subjects for distinguishing primary intergradation from secondary contact. Comparisons among independent hybrid zones or transects that involve the 'same' species pair can also help to distinguish between divergence with gene flow and secondary contact. However, data from replicate hybrid zones or replicate transects do not reveal consistent patterns; in a few cases, patterns of introgression are similar across independent transects, but for many taxa, there is distinct lack of concordance, presumably due to variation in environmental context and/or variation in the genetics of the interacting populations. PMID- 26857440 TI - Multi-color FISH facilitates analysis of cell-type diversification and developmental gene regulation in the Parasteatoda spider embryo. AB - The simultaneous and quantitative analysis of the expression of multiple genes helps to shed light on gene regulatory networks. We established a method for multi-color fluorescence in situ hybridization (mFISH) for the analysis of cell type diversification and developmental gene regulation in the embryo of the spider Parasteatoda tepidariorum. This mFISH technique allowed quadruple staining using four types of labels for RNA probes, digoxigenin, fluorescein, biotin, and dinitrophenyl, together with different fluorescent tyramides. To validate the usability of mFISH, we conducted four experiments. First, we distinguished similar gene expression patterns with mFISH, which showed overlaps and differences in the expression domains of anterior patterning hedgehog (hh), orthodenticle (otd), and labial genes at a cellular resolution. Second, we used mFISH to identify early cell types that are internalized on the anterior side. We found that fork head-positive cells were subdivided into two cell types, 012_A08 positive endoderm cells and twist-positive mesoderm cells. Third, we quantified the ratio of expression levels of the odd-paired (opa) gene in the chelicera and pedipalp segments based on the intensity of mFISH signals. Finally, we combined mFISH with embryonic RNA interference. It was possible to identify opa knockdown cell clones and detect the specific reduction of opa and the upregulation of otd and hh expression levels in the same cell clone that formed in the head region. This study proposes that mFISH is a powerful tool for the cell-level analysis of gene regulation and quantification in the spider model. PMID- 26857439 TI - Taking on the gender challenge in organisations: what does it take? AB - Clear patterns emerged and are summarised on conditions for success in integrating a gender equality perspective across organisational programmes and culture. In short, organisations should consider five key 'ingredients' when designing their approach to integrating a gender equality perspective: (1) have a clear vision of success with measurable indicators; (2) have high-level, consistent, visible support; (3) take an intentional approach deeply rooted in the organisational culture and competencies; (4) ensure accountability at all levels and (5) invest both financial and technical resources. A vibrant community exists in virtually every region of the world of highly experienced gender equality experts that can support organisations on this path. Late adopters of integrating a gender equality perspective can benefit from decades of practice and a robust evidence base which has shifted focus among development organisations from asking 'why' addressing gender inequalities is important to learning 'how' to most effectively do this in programmes, policies, research and organisational culture while building a strong results framework. PMID- 26857438 TI - B-cell acute lymphoblastic leukemia with mature phenotype and MLL rearrangement: report of five new cases and review of the literature. AB - The association between mature-B phenotype and MLL abnormalities in acute lymphoblastic leukemia (ALL) is a very unusual finding; only 14 pediatric cases have been reported so far. We describe the clinical and biological characteristics and outcome of five pediatric cases of newly diagnosed B lineage ALL with MLL abnormalities and mature immunophenotype based on light chain restriction and surface Ig expression. Blasts showed variable expression of CD10/CD34/TdT. MLL abnormalities with no MYC involvement were detected in all patients by G-banding, FISH, and/or RT-PCR. Three patients were treated according to Interfant protocol, one to ALLIC-09, and one received B-NHL-BFM-2004. All patients achieved complete remission and three of them relapsed. Despite the small cohort size, it could be postulated that B lineage ALL with MLL abnormalities and mature phenotype is a distinct entity that differs both from the typical Pro B ALL observed in infants and mature B-ALL with high MYC expression. PMID- 26857441 TI - Mechanisms during suspended solids and phosphate concentration variations in wastewater coagulation process. AB - Coagulation-flocculation process is one of the most commonly used treatment process in water and wastewater treatment. Particles (PA) and phosphates (P) removal are the main objectives in wastewater coagulation. There is a general agreement on the dominant mechanism of PA and P removal during coagulation. While it is agreed that the PA and P removal reactions are competitive and takes place simultaneously, there is no clear understanding on the ratio of distribution of coagulants among the PA and P removal. The ratio can be significantly influenced by the content of PA and P, in addition to other water and coagulant quality factors. This paper attempts to provide a qualitative ratio of coagulant distribution based on PA:P proportion in raw water and OH:Al ratio in coagulants. PMID- 26857444 TI - Current Applications of Chromatographic Methods in the Study of Human Body Fluids for Diagnosing Disorders. AB - Currently, analysis of various human body fluids is one of the most essential and promising approaches to enable the discovery of biomarkers or pathophysiological mechanisms for disorders and diseases. Analysis of these fluids is challenging due to their complex composition and unique characteristics. Development of new analytical methods in this field has made it possible to analyze body fluids with higher selectivity, sensitivity, and precision. The composition and concentration of analytes in body fluids are most often determined by chromatography-based techniques. There is no doubt that proper use of knowledge that comes from a better understanding of the role of body fluids requires the cooperation of scientists of diverse specializations, including analytical chemists, biologists, and physicians. This article summarizes current knowledge about the application of different chromatographic methods in analyses of a wide range of compounds in human body fluids in order to diagnose certain diseases and disorders. PMID- 26857443 TI - Pharmacokinetic studies of solubilized estradiol given vaginally in a novel softgel capsule. AB - OBJECTIVE: To evaluate the bioavailability and safety of a novel vaginal capsule containing solubilized bioidentical 17beta-estradiol for vulvar and vaginal atrophy and compare its pharmacokinetics with that of an approved vaginal estradiol tablet in healthy postmenopausal women. METHODS: Two randomized, single dose, two-way cross-over, relative bioavailability trials compared the pharmacokinetics of a solubilized vaginal estradiol softgel capsule (TX-004HR, test) with that of a vaginal estradiol tablet (Vagifem(r), reference) in postmenopausal women (aged 40-65 years) at 10-MUg and 25-MUg doses. In each study, women were randomly assigned to receive a single dose of the test capsule or reference tablet, followed by a single dose of the alternate drug after a 14 day washout. RESULTS: Thirty-five women completed the 10-MUg study and 36 completed the 25-MUg study. Significantly lower systemic levels of estradiol, estrone, and estrone sulfate at both doses of the test product were observed compared with equivalent doses of the reference product, with lower AUC0-24 and Cmax and earlier tmax. No adverse events were reported in either trial. CONCLUSION: TX-004HR, a novel estradiol vaginal softgel capsule, exhibited significantly lower systemic exposure than equivalent doses of an approved vaginal estradiol tablet at both 10-MUg and 25-MUg doses. Both doses of each product were safe and well-tolerated. PMID- 26857445 TI - A Critical Review of Analytical Methods for Determination of Ertapenem Sodium. AB - Antimicrobials have unquestionable importance in the control of many diseases; however the constant concern with evolution of resistant microorganisms is increasing. Ertapenem sodium is a beta-lactam antibiotic of the carbapenem class that has a broader activity spectrum than most other beta-lactam antimicrobials and is more resistant to the enzyme beta-lactamase, which is the main mechanism of resistance of many bacteria. The progress of microbial resistance to existing antibiotics is alarming. Thus we need to preserve antimicrobials that still have activity against these pathogens. In this context, quality control has a key role to ensure the correct dosage, by contributing preventively to minimize the development of resistant microorganisms. Study of the physico-chemical characteristics of the drug and quantification of the content of the active substance are of fundamental importance for the pharmaceutical industry to ensure the quality of the product sold. This work presents the results of a literature survey of existing methods for ertapenem sodium quantification. Ertapenem sodium can be analyzed by many types of assays; however, HPLC is the most used method. This review will examine the published analytical methods reported for determination of ertapenem sodium in biological fluids and formulations. PMID- 26857446 TI - Analytical Strategies for the Determination of Norepinephrine Reuptake Inhibitors in Pharmaceutical Formulations and Biological Fluids. AB - Norepinephrine reuptake inhibitors (NRIs) are a class of antidepressant drugs that act as reuptake inhibitors for the neurotransmitters norepinephrine and epinephrine. The present review provides an account of analytical methods published in recent years for the determination of NRI drugs. NRIs are atomoxetine, reboxetine, viloxazine and maprotiline. NRIs with less activity at other sites are mazindol, bupropion, tapentadol, and teniloxazine. This review focuses on the analytical methods including chromatographic, spectrophotometric, electroanalytical, and electrophoresis techniques for NRI analysis from pharmaceutical formulations and biological samples. Among all of the published methods, liquid chromatography with UV-vis or MS-MS detection is the most popular technique. The most the common sample preparation techniques in the analytical methods for NRIs include liquid-liquid extraction and solid-phase extraction. Besides the analytical methods for single components, some of the simultaneous determinations are also included in this review. PMID- 26857447 TI - Hospital in the Nursing Home program reduces emergency department presentations and hospital admissions from residential aged care facilities in Queensland, Australia: a quasi-experimental study. AB - BACKGROUND: There has been considerable publicity regarding population ageing and hospital emergency department (ED) overcrowding. Our study aims to investigate impact of one intervention piloted in Queensland Australia, the Hospital in the Nursing Home (HiNH) program, on reducing ED and hospital attendances from residential aged care facilities (RACFs). METHODS: A quasi-experimental study was conducted at an intervention hospital undertaking the program and a control hospital with normal practice. Routine Queensland health information system data were extracted for analysis. RESULTS: Significant reductions in the number of ED presentations per 1000 RACF beds (rate ratio (95 % CI): 0.78 (0.67-0.92); p = 0.002), number of hospital admissions per 1000 RACF beds (0.62 (0.50-0.76); p < 0.0001), and number of hospital admissions per 100 ED presentations (0.61 (0.43 0.85); p = 0.004) were noticed in the experimental hospital after the intervention; while there were no significant differences between intervention and control hospitals before the intervention. Pre-test and post-test comparison in the intervention hospital also presented significant decreases in ED presentation rate (0.75 (0.65-0.86); p < 0.0001) and hospital admission rate per RACF bed (0.66 (0.54-0.79); p < 0.0001), and a non-significant reduction in hospital admission rate per ED presentation (0.82 (0.61-1.11); p = 0.196). CONCLUSIONS: Hospital in the Nursing Home program could be effective in reducing ED presentations and hospital admissions from RACF residents. Implementation of the program across a variety of settings is preferred to fully assess the ongoing benefits for patients and any possible cost-savings. PMID- 26857449 TI - Understanding arsenic mobilization using reactive transport modeling of groundwater hydrochemistry in the Datong basin study plot, China. AB - This paper discusses the reactive transport and evolution of arsenic along a selected flow path in a study plot within the central part of Datong basin. The simulation used the TOUGHREACT code. The spatial and temporal trends in hydrochemistry and mineral volume fraction along a flow path were observed. Furthermore, initial simulation of major ions and pH fits closely to the measured data. The study shows that equilibrium conditions may be attained at different stress periods for each parameter simulated. It is noted that the variations in ionic chemistry have a greater impact on arsenic distribution while reducing conditions drive the mobilization of arsenic. The study concluded that the reduction of Fe(iii) and As(v) and probably SO4/HS cycling are significant factors affecting localized mobilization of arsenic. Besides cation exchange and water-rock interaction, incongruent dissolution of silicates is also a significant control mechanism of general chemistry of the Datong basin aquifer. PMID- 26857448 TI - Women's preferences and mode of delivery in public and private hospitals: a prospective cohort study. AB - BACKGROUND: Rates of caesarean section have steadily increased in most middle- and high-income countries over the last few decades without medical justification. Maternal request is one of the frequently cited non-medical factors contributing to this trend. The objectives of this study were to assess pregnant women's preferences regarding mode of delivery and to compare actual caesarean section rates in the public and private sectors. METHODS: A prospective cohort study was conducted in two public and three private hospitals in Buenos Aires, Argentina. 382 nulliparous pregnant women (183 from the private sector and 199 from the public sector) aged 18 to 35 years, with single pregnancies over 32 weeks of gestational age were enrolled during antenatal care visits between October 2010 and September 2011. We excluded women with pregnancies resulting from assisted fertility, women with known pre-existing major diseases or, with pregnancy complications, or with a medical indication of elective cesarean section. We used two different approaches to assess women's preferences: a survey using a tailored questionnaire, and a discrete choice experiment. RESULTS: Only 8 and 6% of the healthy nulliparous women in the public and private sectors, respectively, expressed a preference for caesarean section. Fear of pain and safety were the most frequently expressed reasons for preferring caesarean section. When reasons for delivery mode were assessed by a discrete choice experiment, women placed the most emphasis on sex after childbirth. Of women who expressed their preference for vaginal delivery, 34 and 40% ended their pregnancies by caesarean section in public and private hospitals, respectively. CONCLUSIONS: The preference for caesarean section is low among healthy nulliparous women in Buenos Aires. The reasons why these women had a rate of more than 35% caesarean sections are unlikely related to their preferences for mode of delivery. PMID- 26857452 TI - A structurally normal fetus at the 11- to 14-week ultrasound does not guarantee a newborn without congenital anomalies: a cohort study. AB - OBJECTIVE: The objective of this study was to analyze the influence of maternal demographic characteristics and abnormal first-trimester sonographic markers on congenital anomalies (CAs) at birth when the fetus is structurally normal at the 11- to 14-week ultrasound. METHODS: This prospective cohort study comprised high risk women undergoing routine antenatal care. Detailed assessments of fetal anatomy and first-trimester sonographic markers were performed at 11-14 weeks of pregnancy. Multilevel regression analysis was used to determine the effects of maternal characteristics and abnormal first-trimester sonographic markers on the incidence of CA at birth. RESULTS: Three hundred and ten patients were evaluated, and 41 patients (13.2%) had an anomalous newborn. The presence of a specific indication at the first-trimester ultrasound (OR: 2.72; CI 95% 1.09-6.74) or a nuchal translucency (NT) thickness greater than 2.5 mm increased the risk of CA at birth by three fold (OR: 3.10; CI 95% 1.07-9.59). High adjusted risks for trisomies 21, 18 and 13 increased the likelihood of having a structurally abnormal newborn by five, twelve and six fold, respectively. CONCLUSION: Increased NT and/or high adjusted risks for trisomies 21, 18, and 13 increase the risk of CA at birth, even in fetuses with a structurally normal 11- to 14-week ultrasound scan. PMID- 26857450 TI - Vaccines in pregnancy: The dual benefit for pregnant women and infants. AB - Maternal immunization has the potential to reduce the burden of infectious diseases in the pregnant woman and her infant. Many countries now recommend immunization against influenza at any stage of pregnancy and against pertussis in the third trimester. Despite evidence of the safety and effectiveness of these vaccines when administered during pregnancy, uptake generally remains low for influenza and moderate for pertussis vaccine. Enhancing confidence in both immunization providers and pregnant women by increasing the evidence-base for the safety and effectiveness of vaccines during pregnancy, improving communication and access by incorporating immunization into standard models of antenatal care are likely to improve uptake. Developing a framework for implementation of vaccines for pregnant women which is cognizant of local and national cultural, epidemiological, behavioral and societal factors will enable a smooth transition and high uptake for new vaccines currently in development for pregnant women. PMID- 26857451 TI - Volatile signature for the early diagnosis of lung cancer. AB - Exhaled breath contains hundreds of volatile organic compounds (VOCs). Several independent researchers point out that the breath of lung cancer patients shows a characteristic VOC-profile which can be considered as lung cancer signature and, thus, used for diagnosis. In this regard, the analysis of exhaled breath with gas sensor arrays is a potential non-invasive, relatively low-cost and easy technique for the early detection of lung cancer. This clinical study evaluated the gas sensor array response for the identification of the exhaled breath of lung cancer patients. This study involved 146 individuals: 70 with lung cancer confirmed by computerized tomography (CT) or positron emission tomography-(PET) imaging techniques and histology (biopsy) or with clinical suspect of lung cancer and 76 healthy controls. Their exhaled breath was measured with a gas sensor array composed of a matrix of eight quartz microbalances (QMBs), each functionalized with a different metalloporphyrin. The instrument produces, for each analyzed sample, a vector of signals encoding the breath (breathprint). Breathprints were analyzed with multivariate analysis in order to correlate the sensor signals to the disease. Breathprints of the lung cancer patients were differentiated from those of the healthy controls with a sensitivity of 81% and specificity of 91%. Similar values were obtained in patients with and without metabolic comorbidities, such as diabetes, obesity and dyslipidemia (sensitivity 85%, specificity 88% and sensitivity 76%, specificity 94%, respectively). The device showed a large sensitivity to lung cancer at stage I with respect to stage II/III/IV (92% and 58% respectively). The sensitivity for stage I did not change for patients with or without metabolic comorbidities (90%, 94%, respectively). Results show that this electronic nose can discriminate the exhaled breath of the lung cancer patients from those of the healthy controls. Moreover, the largest sensitivity is observed for the subgroup of patients with a lung cancer at stage I. PMID- 26857453 TI - Culture, Health, and Science: A Multidisciplinary Liberal Arts Alternative to the Public Health Major. AB - Since the 2003 call by the Institute of Medicine to educate undergraduates in public health, various models have emerged for incorporating public health into the liberal arts and sciences. One model is a professionalized public health major that uses core public health competencies to prepare a workforce of health professionals. A second model offers a broad-based public health major rooted in liberal arts principles, resisting the utilitarian trend toward human capital formation. A third model resists even the label of "public health," preferring instead to introduce undergraduates to many ways of analyzing human health and healing. The multidisciplinary Culture, Health, and Science Program, based on six key commitments for preparing liberal arts students to analyze health and respond to global health challenges, is offered as an alternative to the public health major. PMID- 26857454 TI - Barrier protection via Toll-like receptor 2 signaling in porcine intestinal epithelial cells damaged by deoxynivalnol. AB - Intestinal barrier is the first line of defense inside the body and comprises intercellular tight junction (TJ) proteins that regulate paracellular permeability. Deoxynivalenol (DON), a fungal metabolite often found in the contaminated food of domestic animals, is known to impair intestinal barrier function and may be involved in intestinal inflammation. Unlike in humans and mice, the importance of Toll-like receptor (TLR) 2 expressed in porcine intestinal epithelial cells is largely unclear. Therefore, the aim of the present study was to investigate whether TLR2 stimulation enhances intestinal barrier function and protects against DON exposure. We found that the cells treated with TLR2 ligands decreased the epithelial barrier permeability and enhanced TJ protein expression in intestinal porcine epithelial cells (IPEC-J2). In addition, pretreatment with TLR2 ligand, including Pam3CSK4 (PCSK) and lipoteichoic acid from Bacillus subtilis, prevented DON-induced barrier dysfunction by increasing the expression of TJ proteins via the PI3K-Akt-dependent pathway. It is likely that the DON-disrupted intestinal barrier caused biological changes of immune cells in the lamina propria. Thus, we conducted co-culture of differentiated IPEC J2 cells in the upper well together with peripheral blood mononuclear cells in the bottom well and found that apical TLR2 stimulation of IPEC-J2 cells could alleviate the reduction in cell survival and proliferation of immune cells. Conclusively, TLR2 signaling on intestinal epithelial cells may enhance intestinal barrier function and prevent DON-induced barrier dysfunction of epithelial cells. PMID- 26857455 TI - Small-molecule inhibition of PTPRZ reduces tumor growth in a rat model of glioblastoma. AB - Protein tyrosine phosphatase receptor-type Z (PTPRZ) is aberrantly over-expressed in glioblastoma and a causative factor for its malignancy. However, small molecules that selectively inhibit the catalytic activity of PTPRZ have not been discovered. We herein performed an in vitro screening of a chemical library, and identified SCB4380 as the first potent inhibitor for PTPRZ. The stoichiometric binding of SCB4380 to the catalytic pocket was demonstrated by biochemical and mass spectrometric analyses. We determined the crystal structure of the catalytic domain of PTPRZ, and the structural basis of the binding of SCB4380 elucidated by a molecular docking method was validated by site-directed mutagenesis studies. The intracellular delivery of SCB4380 by liposome carriers inhibited PTPRZ activity in C6 glioblastoma cells, and thereby suppressed their migration and proliferation in vitro and tumor growth in a rat allograft model. Therefore, selective inhibition of PTPRZ represents a promising approach for glioma therapy. PMID- 26857457 TI - Optimizing Sun Protection for Children: Having Our Day in the Sun. PMID- 26857458 TI - Adjuvant chemotherapy versus concurrent chemoradiotherapy for high-risk cervical cancer after radical hysterectomy and systematic lymphadenectomy. AB - BACKGROUND: The aims of this study were to evaluate the efficacy and toxicity of chemotherapy (CT) compared with concurrent chemoradiotherapy (CCRT) after radical hysterectomy and lymphadenectomy in high-risk patients with early-stage cervical cancer and to evaluate whether the radicality of the lymphadenectomy would affect the outcome and toxicity of postoperative adjuvant therapy. METHODS: The cases of all patients (n = 393) with FIGO IB1-IIB cervical cancer who were treated by radical surgery at Shizuoka Cancer Center between January 2002 and December 2013 were reviewed. Of these, 111 patients met the inclusion criteria for this retrospective study: (1) high risk for occurrence due to pathologically confirmed parametrial invasion and/or pelvic lymph node metastasis; (2) postoperative treatment with adjuvant CT or CCRT. The clinical data of these patients were reviewed. RESULTS: Of the 111 patients, 37 and 74 patients underwent CT and CCRT, respectively. The 4-year progression-free survival rate [PFS; 71.7 (CT) vs. 68.3 % (CCRT)] and overall survival rate [76.0 (CT) vs. 82.7 % (CCRT)] did not differ significantly between the two groups. The CT group contained significantly more patients with severe neutropenia than the CCRT group (66.7 vs. 23.0 %, respectively; p < 0.001), and the CCRT group contained significantly more patients with diarrhea than the CT group (10.8 vs. 0 %, respectively; p = 0.04). The patients who had >=40 lymph nodes dissected (>=40 group) had higher PFS than the patients who had <40 lymph nodes dissected (<40 group) (73.2 vs. 64.2 %, respectively), although the difference was not significant. In the CT group, there was no significant association between the number of dissected lymph nodes and severe toxicities. However, in the CCRT group, significantly more vomiting (p = 0.046) and edema (p = 0.046) occurred in the >=40 group than in the <40 group. CONCLUSIONS: Chemotherapy after surgery for high-risk patients had similar efficacy and a different toxicity profile compared with CCRT, and a more radical surgical procedure would improve the survival outcome. However, CCRT was associated with worse toxicity than CT. We advocate a prospective randomized study to compare CT with CCRT for patients with high-risk factors for recurrence. PMID- 26857461 TI - Treatment Approaches in Rodent Models for Autism Spectrum Disorder. AB - Recent years have seen an impressive amount of research devoted to the developing of therapies to treat autism spectrum disorder (ASD). This work has been largely based on rodent models, employing a multitude of genetic and environmental manipulations. Unfortunately, the task of identifying suitable treatments for ASD is extremely challenging, due to a variety of problems specific to the research in this field. Here, we first discuss these problems, including (I) the presence of a large variety of rodent models (often without universal consensus on their validity), (II) the difficulties in choosing the most appropriate behavioural markers to assess the efficacy of possible treatments, (III) the limited knowledge we still have of the neurobiological bases of ASD pathology and of its aetiology, and (IV) the complexity of ASD itself, including a highly heterogeneous group of disorders sometimes with markedly different symptoms (therefore unlikely to be treated with the same approaches). Second, we give a critical overview of the most relevant advances in designing treatments for ASD, focusing on the most commonly used animal model, the laboratory mouse. We include pharmacological and non-pharmacological approaches, underlining their specific advantages, but also their current limitations especially in relation to the problems discussed before. Finally, we highlight the theoretical (e.g. the combination of multiple rather than single treatments) and methodological (e.g. use of single-gene mouse models) approaches that seem more promising to us, suggesting various strategies that can be adopted to simplify the complex field of research on treatments for ASD. PMID- 26857459 TI - Prognostic significance of NADPH oxidase-4 as an indicator of reactive oxygen species stress in human retinoblastoma. AB - BACKGROUND: Reactive oxygen species (ROS) have been shown to enhance the proliferation of cancer cells. NADPH oxidases (NOX4) are a major intracellular source of ROS and are found to be associated with cancer and tumor cell invasion. Therefore, the purpose of this study is to evaluate the expression of NOX4 protein in human retinoblastoma. METHODS: Immunohistochemical expression of NOX4 protein was analyzed in 109 specimens from prospective cases of retinoblastoma and then correlated with clinicopathological parameters and patient survival. Western blotting confirmed and validated the immunoreactivity of NOX4 protein. RESULTS: In our study we found a male preponderance (55.9 %), and 25/109 (22.9 %) were bilateral. Massive choroidal invasion was the histopathological high-risk factor (HRF) most frequently observed, in 42.2 % of the cases. NOX4 protein was expressed in 67.88 % (74/109) of primary retinoblastoma cases and was confirmed by Western blotting. NOX4 was statistically significant with massive choroidal invasion and pathological TNM staging. There was a statistically significant difference in overall survival in patients with NOX4 expression (p = 0.0461). CONCLUSION: This is the first study to show the expression of NOX4 protein in retinoblastoma tumors. Hence, a retinoblastoma tumor may exhibit greater ROS stress. This protein may prove to be useful as a future therapeutic target for improving the management of retinoblastoma. PMID- 26857462 TI - Neuroteratology and Animal Modeling of Brain Disorders. AB - Over the past 60 years, a large number of selective neurotoxins were discovered and developed, making it possible to animal-model a broad range of human neuropsychiatric and neurodevelopmental disorders. In this paper, we highlight those neurotoxins that are most commonly used as neuroteratologic agents, to either produce lifelong destruction of neurons of a particular phenotype, or a group of neurons linked by a specific class of transporter proteins (i.e., dopamine transporter) or body of receptors for a specific neurotransmitter (i.e., NMDA class of glutamate receptors). Actions of a range of neurotoxins are described: 6-hydroxydopamine (6-OHDA), 6-hydroxydopa, DSP-4, MPTP, methamphetamine, IgG-saporin, domoate, NMDA receptor antagonists, and valproate. Their neuroteratologic features are outlined, as well as those of nerve growth factor, epidermal growth factor, and that of stress. The value of each of these neurotoxins in animal modeling of human neurologic, neurodegenerative, and neuropsychiatric disorders is discussed in terms of the respective value as well as limitations of the derived animal model. Neuroteratologic agents have proven to be of immense importance for understanding how associated neural systems in human neural disorders may be better targeted by new therapeutic agents. PMID- 26857460 TI - Metabolic/Proteomic Signature Defines Two Glioblastoma Subtypes With Different Clinical Outcome. AB - Glioblastoma (GBM) is one of the deadliest human cancers. Because of the extremely unfavorable prognosis of GBM, it is important to develop more effective diagnostic and therapeutic strategies based on biologically and clinically relevant subclassification systems. Analyzing a collection of seventeen patient derived glioblastoma stem-like cells (GSCs) by gene expression profiling, NMR spectroscopy and signal transduction pathway activation, we identified two GSC clusters, one characterized by a pro-neural-like phenotype and the other showing a mesenchymal-like phenotype. Evaluating the levels of proteins differentially expressed by the two GSC clusters in the TCGA GBM sample collection, we found that SRC activation is associated with a GBM subgroup showing better prognosis whereas activation of RPS6, an effector of mTOR pathway, identifies a subgroup with a worse prognosis. The two clusters are also differentiated by NMR spectroscopy profiles suggesting a potential prognostic stratification based on metabolic evaluation. Our data show that the metabolic/proteomic profile of GSCs is informative of the genomic/proteomic GBM landscape, which differs among tumor subtypes and is associated with clinical outcome. PMID- 26857464 TI - Identification of beer spoilage microorganisms using the MALDI Biotyper platform. AB - Beer spoilage microorganisms present a major risk for the brewing industry and can lead to cost-intensive recall of contaminated products and damage to brand reputation. The applicability of molecular profiling using matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) in combination with Biotyper software was investigated for the identification of beer spoilage microorganisms from routine brewery quality control samples. Reference mass spectrum profiles for three of the most common bacterial beer spoilage microorganisms (Lactobacillus lindneri, Lactobacillus brevis and Pediococcus damnosus), four commercially available brewing yeast strains (top- and bottom-fermenting) and Dekkera/Brettanomyces bruxellensis wild yeast were established, incorporated into the Biotyper reference library and validated by successful identification after inoculation into beer. Each bacterial species could be accurately identified and distinguished from one another and from over 5600 other microorganisms present in the Biotyper database. In addition, wild yeast contaminations were rapidly detected and distinguished from top- and bottom fermenting brewing strains. The applicability and integration of mass spectrometry profiling using the Biotyper platform into existing brewery quality assurance practices within industry were assessed by analysing routine microbiology control samples from a local brewery, where contaminating microorganisms could be reliably identified. Brewery-isolated microorganisms not present in the Biotyper database were further analysed for identification using LC-MS/MS methods. This renders the Biotyper platform a promising candidate for biological quality control testing within the brewing industry as a more rapid, high-throughput and cost-effective technology that can be tailored for the detection of brewery-specific spoilage organisms from the local environment. PMID- 26857456 TI - Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2. AB - BACKGROUND: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). METHODS: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 * 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 * 10(-12)). CONCLUSIONS: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management. PMID- 26857465 TI - A Pilot Study of the Tongue Pull-Back Exercise for Improving Tongue-Base Retraction and Two Novel Methods to Add Resistance to the Tongue Pull-Back. AB - This pilot study investigated the tongue pull-back (TPB) exercise to improve tongue-base retraction as well as two methods to add resistance to the TPB. Surface electromyography (sEMG) to the submental triangle was used as an indication of tongue-base activity on 13 healthy adults during: (1) saliva swallow, (2) 15 mL water swallow, (3) effortful swallow, (4) unassisted TPB, (5) TPB with added resistance by holding the tongue with gauze (finger-resisted TPB), and (6) TPB with the tongue clipped to a spring-loaded tension resistance device (device-resisted TPB). Order of the exercises was randomized. The exercises fell into two groups-weak and intense. Weak exercises included saliva swallow, water swallow, and unassisted TPB (mean sEMG = 19.07 MUV, p = .593). Intense exercises included effortful swallow, finger-resisted TPB, and device-resisted TPB (mean sEMG = 36.44 MUV, p = .315). Each intense exercise resulted in significantly higher mean sEMG peak amplitude than each weak exercise (p < .05), with one exception; the effortful swallow was not significantly different than the unassisted TPB (p = .171). This study provides preliminary evidence that the unassisted TPB may not be any more helpful for improving tongue-base retraction than normal swallowing. Adding resistance to the TPB by holding the tongue with gauze may be an effective alternative. This study also demonstrates proof-of concept for creating a device to attach to the tongue and provide tension resistance during the TPB exercise. Further research with a more sophisticated design is needed before such a device can be fully developed and implemented clinically. PMID- 26857463 TI - Different cucumber CsYUC genes regulate response to abiotic stresses and flower development. AB - The phytohormone auxin is essential for plant growth and development, and YUCCA (YUC) proteins catalyze a rate-limiting step for endogenous auxin biosynthesis. Despite YUC family genes have been isolated from several species, systematic expression analyses of YUCs in response to abiotic stress are lacking, and little is known about the function of YUC homologs in agricultural crops. Cucumber (Cucumis sativus L.) is a world cultivated vegetable crop with great economical and nutritional value. In this study, we isolated 10 YUC family genes (CsYUCs) from cucumber and explored their expression pattern under four types of stress treatments. Our data showed that CsYUC8 and CsYUC9 were specifically upregulated to elevate the auxin level under high temperature. CsYUC10b was dramatically increased but CsYUC4 was repressed in response to low temperature. CsYUC10a and CsYUC11 act against the upregulation of CsYUC10b under salinity stress, suggesting that distinct YUC members participate in different stress response, and may even antagonize each other to maintain the proper auxin levels in cucumber. Further, CsYUC11 was specifically expressed in the male flower in cucumber, and enhanced tolerance to salinity stress and regulated pedicel and stamen development through auxin biosynthesis in Arabidopsis. PMID- 26857468 TI - Prospects for Flourishing in Contemporary Health Care. AB - This special issue of Health Care Analysis originated in an conference, held in Birmingham in 2014, and organised by the group Think about Health. We introduce the issue by briefly reviewing the understandings of the concept of 'flourishing', and introducing the contributory papers, before offering some reflections on the remaining issues that reflection on flourishing poses for health care provision. PMID- 26857469 TI - Pseudoatrial Flutter Waves -- When a Flutter Is Not a Flutter. PMID- 26857466 TI - De novo transcriptome sequencing and gene expression profiling of spinach (Spinacia oleracea L.) leaves under heat stress. AB - Spinach (Spinacia oleracea) has cold tolerant but heat sensitive characteristics. The spinach variety 'Island,' is suitable for summer periods. There is lack molecular information available for spinach in response to heat stress. In this study, high throughput de novo transcriptome sequencing and gene expression analyses were carried out at different spinach variety 'Island' leaves (grown at 24 degrees C (control), exposed to 35 degrees C for 30 min (S1), and 5 h (S2)). A total of 133,200,898 clean reads were assembled into 59,413 unigenes (average size 1259.55 bp). 33,573 unigenes could match to public databases. The DEG of controls vs S1 was 986, the DEG of control vs S2 was 1741 and the DEG of S1 vs S2 was 1587. Gene Ontology (GO) and pathway enrichment analysis indicated that a great deal of heat-responsive genes and other stress-responsive genes were identified in these DEGs, suggesting that the heat stress may have induced an extensive abiotic stress effect. Comparative transcriptome analysis found 896 unique genes in spinach heat response transcript. The expression patterns of 13 selected genes were verified by RT-qPCR (quantitative real-time PCR). Our study found a series of candidate genes and pathways that may be related to heat resistance in spinach. PMID- 26857467 TI - Proteogenomic-based discovery of minor histocompatibility antigens with suitable features for immunotherapy of hematologic cancers. AB - Pre-clinical studies have shown that injection of allogeneic T cells primed against a single minor histocompatibility antigen (MiHA) could cure hematologic cancers (HC) without causing any toxicity to the host. However, translation of this approach in humans has been hampered by the paucity of molecularly defined human MiHAs. Using a novel proteogenomic approach, we have analyzed cells from 13 volunteers and discovered a vast repertoire of MiHAs presented by the most common HLA haplotype in European Americans: HLA-A*02:01;B*44:03. Notably, out of >6000 MiHAs, we have identified a set of 39 MiHAs that share optimal features for immunotherapy of HCs. These 'optimal MiHAs' are coded by common alleles of genes that are preferentially expressed in hematopoietic cells. Bioinformatic modeling based on MiHA allelic frequencies showed that the 39 optimal MiHAs would enable MiHA-targeted immunotherapy of practically all HLA-A*02:01;B*44:03 patients. Further extension of this strategy to a few additional HLA haplotypes would allow treatment of almost all patients. PMID- 26857470 TI - Pulsed photoacoustic flow imaging with a handheld system. AB - Flow imaging is an important technique in a range of disease areas, but estimating low flow speeds, especially near the walls of blood vessels, remains challenging. Pulsed photoacoustic flow imaging can be an alternative since there is little signal contamination from background tissue with photoacoustic imaging. We propose flow imaging using a clinical photoacoustic system that is both handheld and portable. The system integrates a linear array with 7.5 MHz central frequency in combination with a high-repetition-rate diode laser to allow high speed photoacoustic imaging--ideal for this application. This work shows the flow imaging performance of the system in vitro using microparticles. Both two dimensional (2-D) flow images and quantitative flow velocities from 12 to 75 mm/s were obtained. In a transparent bulk medium, flow estimation showed standard errors of ~7% the estimated speed; in the presence of tissue-realistic optical scattering, the error increased to 40% due to limited signal-to-noise ratio. In the future, photoacoustic flow imaging can potentially be performed in vivo using fluorophore-filled vesicles or with an improved setup on whole blood. PMID- 26857471 TI - High-resolution handheld rigid endomicroscope based on full-field optical coherence tomography. AB - Full-field optical coherence tomography (FF-OCT) is a powerful tool for nondestructive assessment of biological tissue, i.e., for the structural examination of tissue in depth at a cellular resolution. Mostly known as a microscopy device for ex vivo analysis, FF-OCT has also been adapted to endoscopy setups since it shows good potential for in situ cancer diagnosis and biopsy guidance. Nevertheless, all the attempts to perform endoscopic FF-OCT imaging did not go beyond lab setups. We describe here, to the best of our knowledge, the first handheld FF-OCT endoscope based on a tandem interferometry assembly using incoherent illumination. A common-path passive imaging interferometer at the tip of an optical probe makes it robust and insensitive to environmental perturbations, and a low finesse Fabry-Perot processing interferometer guarantees a compact system. A good resolution (2.7 MUm transverse and 6 MUm axial) is maintained through the long distance, small diameter relay optics of the probe, and a good signal-to-noise ratio is achieved in a limited 100 ms acquisition time. High-resolution images and a movie of a rat brain slice have been recorded by moving the contact endoscope over the surface of the sample, allowing for tissue microscopic exploration at 20 m under the surface. These promising ex vivo results open new perspectives for in vivo imaging of biological tissue, in particular, in the field of cancer and surgical margin assessment. PMID- 26857472 TI - RBM4a-regulated splicing cascade modulates the differentiation and metabolic activities of brown adipocytes. AB - RNA-binding motif protein 4a (RBM4a) reportedly reprograms splicing profiles of the insulin receptor (IR) and myocyte enhancer factor 2C (MEF2C) genes, facilitating the differentiation of brown adipocytes. Using an RNA-sequencing analysis, we first compared the gene expressing profiles between wild-type and RBM4a(-/-) brown adipocytes. The ablation of RBM4a led to increases in the PTBP1, PTBP2 (nPTB), and Nova1 proteins, whereas elevated RBM4a reduced the expression of PTBP1 and PTBP2 proteins in brown adipocytes through an alternative splicing coupled nonsense-mediated decay mechanism. Subsequently, RBM4a indirectly shortened the half-life of the Nova1 transcript which was comparatively stable in the presence of PTBP2. RBM4a diminished the influence of PTBP2 in adipogenic development by reprogramming the splicing profiles of the FGFR2 and PKM genes. These results constitute a mechanistic understanding of the RBM4a-modulated splicing cascade during the brown adipogenesis. PMID- 26857475 TI - Quantum entanglement of identical particles by standard information-theoretic notions. AB - Quantum entanglement of identical particles is essential in quantum information theory. Yet, its correct determination remains an open issue hindering the general understanding and exploitation of many-particle systems. Operator-based methods have been developed that attempt to overcome the issue. Here we introduce a state-based method which, as second quantization, does not label identical particles and presents conceptual and technical advances compared to the previous ones. It establishes the quantitative role played by arbitrary wave function overlaps, local measurements and particle nature (bosons or fermions) in assessing entanglement by notions commonly used in quantum information theory for distinguishable particles, like partial trace. Our approach furthermore shows that bringing identical particles into the same spatial location functions as an entangling gate, providing fundamental theoretical support to recent experimental observations with ultracold atoms. These results pave the way to set and interpret experiments for utilizing quantum correlations in realistic scenarios where overlap of particles can count, as in Bose-Einstein condensates, quantum dots and biological molecular aggregates. PMID- 26857473 TI - Incidence of elbow injuries in adolescent baseball players: screening by a low field magnetic resonance imaging system specialized for small joints. AB - PURPOSE: The aim of this preliminary study was to examine the capability of screening for elbow injuries induced by baseball using a low field small joint MRI system. MATERIALS AND METHODS: Sixty-two players in the 4th-6th elementary school grades, with ages ranging from 9 to 12 years, participated in this study. Screening for elbow injuries was performed using a low-magnetic-field (0.2-T) magnetic resonance imaging (MRI) system designed for examinations of small joints of the extremities. Gradient-echo coronal, sagittal, and short-tau inversion recovery (STIR) coronal images of the dominant arm used for pitching were obtained to identify medial collateral ligament (MCL) injuries with or without avulsion fracture and osteochondritis dissecans. RESULTS: All 62 examinations were performed successfully, with 26 players (41.9 %) showing positive findings, all being confined to the MCL. No child showed bone damage. All criteria in the MRI evaluation of injuries showed high agreement rates and kappa values between two radiologists. CONCLUSION: Screening for early detection of elbow injuries in junior Japanese baseball players can be successfully performed using a low-field MRI system specialized for small joints. The percentage of MCL injury without avulsion fracture was unexpectedly high (41.9 %). PMID- 26857476 TI - First feed affects the expressions of microRNA and their targets in Atlantic cod. AB - To our knowledge, there is no report on microRNA (miRNA) expression and their target analysis in relation to the type of the first feed and its effect on the further growth of fish. Atlantic cod (Gadus morhua) larvae have better growth and development performance when fed natural zooplankton as a start-feed, as compared with those fed typical aquaculture start-feeds. In our experiment, two groups of Atlantic cod larvae were fed reference feed (zooplankton, mostly copepods, filtered from a seawater pond) v. aquaculture feeds: enriched rotifers (Brachionus sp.) and later brine shrimp (Artemia salina). We examined the miRNA expressions of six defined developmental stages as determined and standardised by body length from first feeding for both diet groups. We found eight miRNA (miR-9, miR-19a, miR-130b, miR-146, miR-181a, miR-192, miR-206 and miR-11240) differentially expressed between the two feeding groups in at least one developmental stage. We verified the next-generation sequencing data using real time RT-PCR. We found 397 putative targets (mRNA) to the differentially expressed miRNA; eighteen of these mRNA showed differential expression in at least one stage. The patterns of differentially expressed miRNA and their putative target mRNA were mostly inverse, but sometimes also concurrent. The predicted miRNA targets were involved in different pathways, including metabolic, phototransduction and signalling pathways. The results of this study provide new nutrigenomic information on the potential role of miRNA in mediating nutritional effects on growth during the start-feeding period in fish larvae. PMID- 26857477 TI - Dark States in the Light-Harvesting complex 2 Revealed by Two-dimensional Electronic Spectroscopy. AB - Energy transfer and trapping in the light harvesting antennae of purple photosynthetic bacteria is an ultrafast process, which occurs with a quantum efficiency close to unity. However the mechanisms behind this process have not yet been fully understood. Recently it was proposed that low-lying energy dark states, such as charge transfer states and polaron pairs, play an important role in the dynamics and directionality of energy transfer. However, it is difficult to directly detect those states because of their small transition dipole moment and overlap with the B850/B870 exciton bands. Here we present a new experimental approach, which combines the selectivity of two-dimensional electronic spectroscopy with the availability of genetically modified light harvesting complexes, to reveal the presence of those dark states in both the genetically modified and the wild-type light harvesting 2 complexes of Rhodopseudomonas palustris. We suggest that Nature has used the unavoidable charge transfer processes that occur when LH pigments are concentrated to enhance and direct the flow of energy. PMID- 26857478 TI - Predicting pseudocyst formation following pancreatic trauma in pediatric patients. AB - BACKGROUND: There are insufficient data on pre-screening for pancreatic pseudocysts (PC) following pancreatic trauma. This study investigated the use of radiological and laboratory testing for predicting the development of pancreatic pseudocysts after trauma. MATERIALS AND METHODS: The clinical records of all pediatric patients presenting with pancreatic trauma between January 2003 and December 2014 were reviewed retrospectively. Patients with American Association for the Surgery of Trauma (AAST) scores of Grade 3-5 were enrolled. The patients were divided into groups that developed [Group 1 (n = 20)] and did not develop [Group 2 (n = 18)] PC. The patients were evaluated in terms of their baseline characteristics, additional injuries, Injury Severity Score (ISS), pancreatic injury site, blood amylase levels 2 h and 10-15 days after the trauma, clinical presentation, and duration of intensive care unit (ICU) stay. FINDINGS: We followed 38 patients. Of the patients in Group 1, 70 % had an injury to the tail of the pancreas. The ISS trauma scores and durations of hospitalization and ICU stay were significantly greater in Group 2 (p < 0.05). The mean blood amylase level on Day 1 was 607 U/L (range 183-801 U/L) in Group 1 and 314 U/L (range 25 631 U/L) in Group 2; the respective levels on Day 10 were 838 U/L (range 123-2951 U/L) and 83.2 U/L (range 35-164 U/L). The serum amylase levels were significantly higher (p < 0.001) in Group 1 than in Group 2 on Days 1 and 10. Four patients developed complications and two patients died. CONCLUSION: Pancreatic pseudocyst formation is more likely in patients with AAST Grade 3 pancreatic injury, also serum amylase levels ten times greater than normal 2 h after the trauma, and persistently elevated serum amylase levels 10-15 days following the trauma. PMID- 26857479 TI - Depressive Symptom Inventory Suicidality Subscale: Optimal Cut Points for Clinical and Non-Clinical Samples. AB - : Suicide is a major cause of death in adulthood and specifically in patients suffering from mental illnesses. The Depressive Symptom Inventory Suicidality Subscale (DSI-SS) is widely used to detect and prevent suicidal ideation. The aim of the present study was to determine optimal cut points for the DSI-SS in different populations. We analysed the data of one population-based sample (n = 532), one outpatient sample (n = 180) and one inpatient sample (n = 244). Internal consistency, convergent validity and optimal cut points according to receiver operating characteristics were calculated. In all samples, we found excellent item-total correlations and internal consistencies for the DSI-SS. Zero order correlations between the DSI-SS and theoretically related constructs showed positive correlation coefficients, ranging from 0.50 to 0.67. The DSI-SS differentiated well between patients with and without suicide attempts in the population-based sample, but less so in the inpatient sample and only marginally in the outpatient sample. A bootstrapping analysis showed some variability in the cut points that emerged as optimal, but there was no overlap between the different samples. The specific cut points that we identified may be used to improve the diagnostic utility of the DSI-SS and the chance to detect suicidal ideation. Copyright (c) 2016 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: We developed cut points for the Depressive Symptom Inventory Suicidality Subscale, to improve the early and valid detection of suicidal ideation by this measure. The cut points that were identified as optimal varied between the samples. The cut points differentiated well in a non-clinical sample, but less well in outpatient and inpatient samples. PMID- 26857481 TI - Interpersonal Trust and Ability of Elderly Victims to Perform Activities of Daily Living in the Ya'an Earthquake Reconstruction Area, China. AB - OBJECTIVE: The present study aimed to investigate the effect of the socioeconomic status and interpersonal trust of elderly victims of the Ya'an earthquake on their ability to perform activities of daily living (ADLs). METHODS: Random sampling was done in the 8 counties of Ya'an in Sichuan, China (N=691). A multistage random sampling method was used. Samples were selected from counties, towns, and villages, respectively. The Faith in People Scale was used to measure interpersonal trust, and the Barthel ADL Index was used to measure ADLs. Both scales have strong reliability. RESULTS: A total of 37.34% of elderly earthquake victims relied on others moderately to live, and their self-rating of interpersonal trust was relatively unfavorable. Factors such as being female, being widowed, having a low educational level, and income negatively affected ADLs, among which education had the greatest influence. Interpersonal trust was vital in enhancing the level of ADLs of elderly victims. CONCLUSIONS: A high level of interpersonal trust can significantly improve the ADLs of elderly persons. However, this may be achieved by weakening the negative effect of deteriorating social structure of victims. Attention should be focused on elderly victims whose social network worsens to improve their ADLs. (Disaster Med Public Health Preparedness. 2016;page 1 of 7). PMID- 26857480 TI - Reversing the testing effect by feedback: Behavioral and electrophysiological evidence. AB - The testing effect refers to the finding that retrieval practice of previously studied information enhances its long-term retention more than restudy practice does. Recent work showed that the testing effect can be dramatically reversed when feedback is provided to participants during final recall testing (Storm, Friedman, Murayama, & Bjork, 2014). Following this prior work, in this study, we examined the reversal of the testing effect by investigating oscillatory brain activity during final recall testing. Twenty-six healthy participants learned cue target word pairs and underwent a practice phase in which half of the items were retrieval practiced and half were restudy practiced. Two days later, two cued recall tests were administered, and immediate feedback was provided to participants in Test 1. Behavioral results replicated the prior work by showing a testing effect in Test 1, but a reversed testing effect in Test 2. Extending the prior work, EEG results revealed a feedback-related effect in alpha/lower-beta and retrieval-related effects in slow and fast theta power, with practice condition modulating the fast theta power effect for items that were not recalled in Test 1. The results indicate that the reversed testing effect can arise without differential strengthening of restudied and retrieval-practiced items via feedback learning. Theoretical implications of the findings, in particular with respect to the distribution-based bifurcation model of testing effects (Kornell, Bjork, & Garcia, 2011), are discussed. PMID- 26857482 TI - Selection signatures in Shetland ponies. AB - Shetland ponies were selected for numerous traits including small stature, strength, hardiness and longevity. Despite the different selection criteria, Shetland ponies are well known for their small stature. We performed a selection signature analysis including genome-wide SNPs of 75 Shetland ponies and 76 large sized horses. Based upon this dataset, we identified a selection signature on equine chromosome (ECA) 1 between 103.8 Mb and 108.5 Mb. A total of 33 annotated genes are located within this interval including the IGF1R gene at 104.2 Mb and the ADAMTS17 gene at 105.4 Mb. These two genes are well known to have a major impact on body height in numerous species including humans. Homozygosity mapping in the Shetland ponies identified a region with increased homozygosity between 107.4 Mb and 108.5 Mb. None of the annotated genes in this region have so far been associated with height. Thus, we cannot exclude the possibility that the identified selection signature on ECA1 is associated with some trait other than height, for which Shetland ponies were selected. PMID- 26857483 TI - A photo-cleavable biotin affinity tag for the facile release of a photo crosslinked carbohydrate-binding protein. AB - The use of photo-crosslinking glycoprobes represents a powerful strategy for the covalent capture of labile protein complexes and allows detailed characterization of carbohydrate-mediated interactions. The selective release of target proteins from solid support is a key step in functional proteomics. We envisaged that light activation can be exploited for releasing labeled protein in a dual photo affinity probe-based strategy. To investigate this possibility, we designed a trifunctional, galactose-based, multivalent glycoprobe for affinity labeling of carbohydrate-binding proteins. The resulting covalent protein-probe adduct is attached to a photo-cleavable biotin affinity tag; the biotin moiety enables specific presentation of the conjugate on streptavidin-coated beads, and the photolabile linker allows the release of the labeled proteins. This dual probe promotes both the labeling and the facile cleavage of the target protein complexes from the solid surfaces and the remainder of the cell lysate in a completely unaltered form, thus eliminating many of the common pitfalls associated with traditional affinity-based purification methods. PMID- 26857484 TI - A novel dietary improvement strategy: examining the potential impact of community supported agriculture membership. AB - OBJECTIVE: To investigate the use of community-supported agriculture (CSA) as an employer-based health promotion intervention. DESIGN: Quasi-experimental study using a convenience sample of employees at three employers. SETTING: Participants and controls from three Minnesota employers completed baseline and follow-up health assessments and surveys about their experiences with CSA. SUBJECTS: A total of 324 participants purchased a CSA share and were eligible for study inclusion. Study participants were matched by age, sex, employer and occupation to a non-randomized control group of individuals who did not purchase a CSA share but completed health assessments during the same time frame as the study participants. RESULTS: The majority of participants were female, white, middle aged and highly educated. The most common reason for purchasing a CSA share was a desire for fresh food, and the majority of participants were satisfied with their experience. Participants reported a significant increase in the number of vegetables present in the household and the frequency of family meals. The frequency of eating out decreased significantly, especially at fast-food restaurants. Participants also reported an increase in the amount and variety of produce consumed. However, health assessment data did not show significant changes in dietary intake, health status or BMI. CONCLUSIONS: CSA participation was associated with improvement in some aspects of the household environment and dietary behaviours. Further research is needed to determine whether employer based CSA interventions may also lead to improvements in dietary intake and health. PMID- 26857485 TI - Patients Want to Meet With Imaging Experts. AB - PURPOSE: The evolving health care landscape demands a multidisciplinary approach to care and increased emphasis on patient engagement. Radiologists may play an important role in this respect, by improving patient agency and understanding through direct patient interaction. The purpose of this study is to assess patient preferences and perceptions regarding direct communication with radiologists, focusing on a medically underserved demographic. METHODS: Our institutional review board approved this HIPAA-compliant study. English- and/or Spanish-speaking adults undergoing imaging studies across two tertiary-care hospitals and a busy outpatient center were surveyed over a consecutive two-month period, to assess knowledge of the role of a radiologist, interest in, and perceived benefits of reviewing examination results with imaging experts. RESULTS: A total of 628 surveys were completed: 20% of total respondents accurately identified the role of radiologists; 28% identified radiologists as doctors. A total of 68% of respondents expressed an interest in receiving imaging results immediately, or whenever results became available, regardless of when referring physicians received results. An interest in reviewing imaging results with an expert was indicated by 81% of respondents; 88% anticipated that reviewing imaging results with an expert would be beneficial. Although 58% of respondents indicated that they might be willing to pay out of pocket for such a service, 50% selected $0 when asked to indicate an amount. CONCLUSIONS: Although most patients do not know the role of radiologists, they want immediate results, and perceive value in consulting directly with imaging experts. PMID- 26857486 TI - A Female Faculty Development Program for Radiology. PMID- 26857487 TI - Asset Protection and Estate Planning: Considerations for Establishing a Trust. PMID- 26857489 TI - Immune malfunction in the GPR39 zinc receptor of knockout mice: Its relationship to depressive disorder. AB - Depression is a serious psychiatric disorder affecting not only the monaminergic, glutamatergic, and GABAergic neurosystems, but also the immune system. Patients suffering from depression show disturbance in the immune parameters as well as increased susceptibility to infections. Zinc is well known as an anti inflammatory agent, and its link with depression has been proved, zinc deficiency causing depression- and anxiety-like behavior with immune malfunction. It has been discovered that trace-element zinc acts as a neurotransmitter in the central nervous system via zinc receptor GPR39. In this study we investigated whether GPR39 knockout would cause depressive-like behavior as measured by the forced swim test, and whether these changes would coexist with immune malfunction. In GPR39 knockout mice versus a wild-type control we found: i) depressive-like behavior; ii) significantly reduced thymus weight; (iii) reduced cell viability of splenocytes; iv) reduced proliferative response of splenocytes; and v) increased IL-6 production of splenocytes after ConA stimulation and decreased IL 1b and IL-6 release after LPS stimulation. The results indicate depressive-like behavior in GPR39 KO animals with an immune response similar to that observed in depressive disorder. Here for the first time we show immunological changes under GPR39-deficient conditions. PMID- 26857488 TI - Immunopathology of Japanese macaque encephalomyelitis is similar to multiple sclerosis. AB - Japanese macaque encephalomyelitis (JME) is an inflammatory demyelinating disease that occurs spontaneously in a colony of Japanese macaques (JM) at the Oregon National Primate Research Center. Animals with JME display clinical signs resembling multiple sclerosis (MS), and magnetic resonance imaging reveals multiple T2-weighted hyperintensities and gadolinium-enhancing lesions in the central nervous system (CNS). Here we undertook studies to determine if JME possesses features of an immune-mediated disease in the CNS. Comparable to MS, the CNS of animals with JME contain active lesions positive for IL-17, CD4+ T cells with Th1 and Th17 phenotypes, CD8+ T cells, and positive CSF findings. PMID- 26857491 TI - The correlation of HLA-G with multiple sclerosis. PMID- 26857490 TI - Suppression of microglia activation after hypoxia-ischemia results in age dependent improvements in neurologic injury. AB - We previously found increased microglial proliferation and pro-inflammatory cytokine release in infant mice compared to juvenile mice after hypoxia-ischemia (HI). The aim of the current study was to assess for differences in the effect of microglial suppression on HI-induced brain injury in infant and juvenile mice. HI was induced in neonatal (P9) and juvenile (P30) mice and minocycline or vehicle was administered at 2h and 24h post-HI. P9 minocycline-treated mice demonstrated early but transient improvements in neurologic injury, while P30 minocycline treated mice demonstrated sustained improvements in cerebral atrophy and Morris Water Maze performance at 60days post-HI. PMID- 26857492 TI - MSRV envelope protein is a potent, endogenous and pathogenic agonist of human toll-like receptor 4: Relevance of GNbAC1 in multiple sclerosis treatment. AB - Multiple sclerosis associated retrovirus envelope protein (MSRV-Env) was repeatedly detected in brain lesions and blood of multiple sclerosis (MS) patients. We performed the first pharmacological characterisation of MSRV-Env on recombinant and native human TLR4. MSRV-Env is a full and highly potent TLR4 agonist of endogenous origin. MSRV-Env induces TLR4-dependent pro-inflammatory stimulation of immune cells in vitro and in vivo, and impairs oligodendrocytes precursor cells differentiation to myelinating oligodendrocytes. MSRV-Env may play a role in chronic inflammation and impaired remyelination in MS. GNbAC1, a selective monoclonal antibody, antagonizes MSRV-Env pathogenic effects and represents an innovative therapeutic approach of MS. PMID- 26857493 TI - Requirement of CD30 expression on CD4 T cells in the pathogenesis of experimental autoimmune encephalomyelitis. AB - CD30, a member of the tumor necrosis factor receptor superfamily, is expressed preferentially by effector or memory helper T cells. Here we show that experimental autoimmune encephalomyelitis (EAE) is ameliorated with markedly reduced induction of antigen-specific Th1 and Th17 cells in CD30 knockout mice. Passive EAE indicated that CD30 on non-hematopoietic parenchymal cell is not required and mixed bone marrow chimera experiments revealed that CD30 signaling on CD4 T cells amplified the development of antigen-specific and encephalitogenic CD4 T cells. Thus, CD30 expression on CD4 T cells is critically involved in the pathogenesis of central nervous system autoimmunity. PMID- 26857494 TI - B cells from relapsing remitting multiple sclerosis patients support neuro antigen-specific Th17 responses. AB - B cells are highly potent antigen presenting cells of their cognate antigens. However, it remains unknown whether B cells can orchestrate Th17-mediated responses against neuro-antigens. We report that MS patients and healthy donors had a similar frequency of antigen-specific Th1 and Th17 cells, and distribution of T effector and T central memory cells. Notwithstanding these similarities, the application of an in vitro assay demonstrated that the B cells derived from a subset of MS patients exhibited the capability of coordinating Th17 responses directed toward neuro-antigens. These observations underscore the B cell's contribution to the putative underpinnings of multiple sclerosis. PMID- 26857495 TI - C-C chemokine receptor type 4 antagonist Compound 22 ameliorates experimental autoimmune encephalomyelitis. AB - Chemokines and chemokine receptors play important roles in the immune response. We previously reported the pathogenic role of C-C chemokine receptor type 4 (CCR4) in experimental autoimmune encephalomyelitis (EAE). Here, we examined whether CCR4 antagonism modulates the disease course of EAE. Wild-type and CCR4 knockout mice were induced EAE and were administered Compound 22, an antagonist of CCR4. Compound 22 significantly ameliorated the severity of EAE in wild-type mice, but not in the CCR4-knockout mice. Compound 22 inhibited Th1 and Th17 polarization of antigen-induced T-cell responses. Therefore, CCR4 antagonists might be potential therapeutic agents for multiple sclerosis. PMID- 26857497 TI - Analysis of CH25H in multiple sclerosis and neuromyelitis optica. AB - Oxysterols produced by CH25H during cholesterol metabolism have been shown to play an important role in the immune response. In this study we report the genetic characterization of CH25H in patients diagnosed with multiples sclerosis (MS) or neuromyelitis optica (NMO), for the identification of genetic variants affecting disease susceptibility and course. Exome analysis in 212 MS and 14 NMO patients identified a rare CH25H p.Q17H mutation in two NMO patients of Asian ancestry. In addition, association analysis of common CH25H variants identified a nominally significant association with MS patients presenting a clinical course consistent with primary progressive disease. PMID- 26857496 TI - IL-12Rbeta2 has a protective role in relapsing-remitting experimental autoimmune encephalomyelitis. AB - IL-12Rbeta2 is a common receptor subunit of heterodimeric receptors for IL-12 and IL-35, two cytokines that are implicated in immunopathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We evaluated the role of IL-12Rbeta2 in relapsing-remitting EAE (RR-EAE). IL 12Rbeta2-deficient SJL/J mice developed markedly more severe clinical EAE, and had greater mortality and more severe relapses compared with wild-type controls. IL-12Rbeta2-deficient EAE mice also had more infiltrating mononuclear cells in the CNS, as well as higher T cell proliferative capacity and decreased IFN-gamma production at the periphery. These findings demonstrate a protective role of IL 12Rbeta2 in RR-EAE. PMID- 26857499 TI - Autoantibodies to tetraspanins (CD9, CD81 and CD82) in demyelinating diseases. AB - Tetraspanin family proteins, CD9, CD81 and CD82 are expressed in the oligodendrocytes and Schwann cells. We investigated autoantibodies to tetraspanin proteins in patients with demyelinating diseases. Sera were collected from 119 multiple sclerosis patients, 19 neuromyelitis optica, 42 acute inflammatory demyelinating polyneuropathy, 23 chronic inflammatory demyelinating polyneuropathy and 13 acute motor axonal neuropathy as well as 55 healthy controls. Few multiple sclerosis and acute inflammatory demyelinating polyneuropathy patients had autoantibodies that were weakly reactive to CD9 or CD81 but the significance is unclear. It is unlikely that these autoantibodies are pathogenic or serve as potential biomarkers in demyelinating diseases. PMID- 26857498 TI - MxA mRNA expression as a biomarker of interferon beta response in multiple sclerosis patients. AB - Myxovirus resistance protein A (MxA) is a molecule induced after interferon-beta injection. The aim of this study was to investigate whether MxA determination one year after starting interferon-beta can predict treatment response in multiple sclerosis patients. MxA mRNA expression was evaluated in blood samples obtained at baseline and at month 12. Clinical variables were prospectively recorded. A threshold of 5 was defined to establish MxA induction. On survival analysis, time to the next relapse and to EDSS progression were significantly longer in patients showing MxA induction, suggesting that MxA induction after one year may be useful to identify interferon-beta responders. PMID- 26857500 TI - Longitudinal epitope mapping in MuSK myasthenia gravis: implications for disease severity. AB - Muscle weakness in MuSK myasthenia gravis (MG) is caused predominantly by IgG4 antibodies which block MuSK signalling and destabilize neuromuscular junctions. We determined whether the binding pattern of MuSK IgG4 antibodies change throughout the disease course ("epitope spreading"), and affect disease severity or treatment responsiveness. We mapped the MuSK epitopes of 255 longitudinal serum samples of 53 unique MuSK MG patients from three independent cohorts with ELISA. Antibodies against the MuSK Iglike-1 domain determine disease severity. Epitope spreading outside this domain did not contribute to disease severity nor to pyridostigmine responsiveness. This provides a rationale for epitope specific treatment strategies. PMID- 26857501 TI - Metal ions potentiate microglia responsiveness to endotoxin. AB - Oral metal exposure has been associated with diverse adverse reactions, including neurotoxicity. We showed previously that dentally applied metals activate dendritic cells (MoDC) via TLR4 (Ni, Co, Pd) and TLR3 (Au). It is still unknown whether the low levels of dental metals reaching the brain can trigger local innate cells or prime them to become more responsive. Here we tested whether dentally applied metals (Cr, Fe, Co, Ni, Cu, Zn, Au, Hg) activate primary human microglia in vitro and, as a model, monocytic THP-1-cells, in high non-toxic as well as near-physiological concentrations. In addition the effects of 'near physiological' metal exposure on endotoxin (LPS) responsiveness of these cells were evaluated. IL-8 and IL-6 production after 24h was used as read out. In high, non-toxic concentrations all transition metals except Cr induced IL-8 and IL-6 production in microglia, with Ni and Co providing the strongest stimulation. When using near-physiological doses (up to 10* the normal plasma concentration), only Zn and Cu induced significant IL-8 production. Of note, the latter metals also markedly potentiated LPS responsiveness of microglia and THP-1 cells. In conclusion, transition metals activate microglia similar to MoDCs. In near physiological concentrations Zn and Cu are the most effective mediators of innate immune activation. A clear synergism between innate responses to Zn/Cu and LPS was observed, shedding new light on the possible relation between oral metal exposure and neurotoxicity. PMID- 26857502 TI - Differentiation of neuromyelitis optica spectrum disorders from ultra longitudinally extensive transverse myelitis in a cohort of Chinese patients. AB - This study aimed to differentiate neuromyelitis optica spectrum disorders (NMOSD) from other causes in cases of ultra-longitudinally extensive transverse myelitis (uLETM). We retrospectively analyzed thirty-three Chinese patients with uLETM hospitalized in the China-Japan Friendship Hospital. The patients were divided into NMOSD (n=21) and non-NMOSD (n=12) groups. The NMOSD group exhibited significantly more comorbidity compared with the non-NMOSD group; moreover, the NMOSD group uniquely exhibited intractable vomiting and hiccups (IVH). The prevalence rates of cervicothoracic, area postrema (AP), and other circumventricular organ (CVO) lesions were significantly increased in the NMOSD group compared with the non-NMOSD group. Moreover, uLETM was strongly associated with NMOSD. These novel findings indicate that CVO lesions, including AP, and particularly when combined with clinical IVH, may represent a useful discriminator to differentiate NMOSD. PMID- 26857503 TI - Role of orexin-A in experimental autoimmune encephalomyelitis. AB - The aim of this study was to evaluate the effects of orexin-A (OX-A) on behavioral and pathological parameters and on gene expression of some multiple sclerosis-related peptides in a model of experimental autoimmune encephalomyelitis (EAE). EAE was induced by subcutaneous administration of MOG 35 55. Following immunization, the treatment was initiated by using SB.334867 (orexin-1 receptor antagonist) and/or OX-A. Locomotor activity and exploratory behaviors were monitored using open field and T-maze continuous alternation task (T-CAT) respectively. Pain sensitivity was assessed by hot-plate test. Histopathological assessments were performed by H&E staining. The expression of TGF-beta, MBP, MMP-9, IL-12, iNOS and MCP-1 were measured using real-time PCR method in lumbar spinal cord. OX-A administration in EAE mice remarkably attenuated the clinical symptoms, increased latency response in hot plate test, inhibited infiltration of inflammatory cells, up-regulated mRNA expression of TGF beta as well as MBP and down-regulated mRNA expression of iNOS, MMP-9 and IL-12. In contrast SB.334867 administration in EAE mice deteriorated the clinical symptoms, decreased the alternation in T-CAT, increased infiltration of inflammatory cells, down-regulated mRNA expression of TGF-beta and MBP and up regulated mRNA expression of iNOS. Results of this study suggest that the orexinergic system might be involved in pathological development of EAE. These findings suggest orexinergic system as a potential target for treatment of multiple sclerosis. PMID- 26857504 TI - Humoral cross reactivity between alpha-synuclein and herpes simplex-1 epitope in Parkinson's disease, a triggering role in the disease? AB - Environmental factors are implicated in the development of Parkinson's disease (PD). We have investigated on the role of molecular mimicry between HSV1 and alpha-synuclein that could foster the progression of PD. The antibody response against homologous peptides in PD patients and healthy controls was evaluated, showing that these antibodies are highly prevalent among PD patients to healthy controls. The competitive assay demonstrated cross-reactivity between HSV1 and human alpha-synuclein peptides. The results may suggest the hypothesis of the involvement of HSV1 in stimulating the immune cells against the neurons of the substantia nigra as a consequence of the cross reactivity. PMID- 26857505 TI - Role of cox-2 mediated neuroinflammation on the neurodegeneration and cognitive impairments in colchicine induced rat model of Alzheimer's Disease. AB - The neurodegeneration in colchicine induced AD (cAD) rats is linked with neuroinflammation. The inducible cox-2 present in the brain may participate in the neuroinflammatory process related to progressive neurodegeneration in cAD rats. The aim of this study is to investigate the role of cox-2 in the neurodegeneration and cognitive impairments in cAD rats. The parameters of memory (working and reference memory), inflammatory markers [IL-1beta, TNF-alpha, prostaglandin E2 (PGE2), cox-2 level] and histopathology of hippocampus were measured after 21-day of i.c.v. colchicine injection in rats and compared with that of control and sham operated rats. These parameters were also measured in these 3 different groups of rats after p.o. administration of 3 different doses of etoricoxib, a cox 2 inhibitor. The impairments of working and reference memory were associated with neuroinflammation and neurodegeneration in the hippocampus and increased cox-2 and PGE2 levels in hippocampus in cAD. Administration of etoricoxib in cAD rats resulted in recovery of memory impairments, neurodegeneration and neuroinflammation in hippocampus and inhibition of cox-2 and PGE2 levels in hippocampus. It appears from the results that activation of cox-2 in cAD is related to neuroinflammation involved in neurodegeneration. Colchicine induced initial neurodegeneration may trigger cascade of events for a progressive neurodegeneration where cox-2 activation plays a critical role. Moreover, this cox-2 mediated neurodegeneration is related to impairments of memory parameters. Thus, the present study showed that the impairments of memory and neurodegeneration in the hippocampus of cAD in 21-day study are mediated by cox-2 induced neuroinflammation. PMID- 26857508 TI - Self-Powered Bipolar Electrochromic Electrode Arrays for Direct Displaying Applications. AB - Here we report a self-powered-bipolar-electrochromic-electrode (termed SP-BP-EC E) array for the displaying applications including catalyst screening, catalytic activity measurement, and enzyme substrate quantification. By replacing the directional (or active) power source with the isotropic chemical energy to drive the bipolar electrochemical reaction, the driving background signal, bipolar electrode (BPE) background signal, uneven reporting signal and the influence of electrolysis which commonly appear in traditional bipolar systems are effectively eliminated from origin. Thus, the reporting signals from the SP-BP-EC-E arrays can be more direct and reliable to reflect the target nature. Such a SP-BP-EC-E platform exhibits a sensitive response toward the fast analysis of commercial Pt black catalyst, NiPdAu hollow nanospheres, glucose dehydrogenase, and glucose. To our knowledge, this test paper-like SP-BP-EC-E is the simplest platform for high throughput screening to date, which offers a very convenient approach for nonprofessional people to access the complicated screening and fast analysis of the electrocatalysts and biocatalyst activity and quantification of enzymatic substrates. PMID- 26857507 TI - Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014. AB - Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti-MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans. PMID- 26857506 TI - Dendritic Spine Loss and Chronic White Matter Inflammation in a Mouse Model of Highly Repetitive Head Trauma. AB - Mild traumatic brain injury (mTBI) is an emerging risk for chronic behavioral, cognitive, and neurodegenerative conditions. Athletes absorb several hundred mTBIs each year; however, rodent models of repeat mTBI (rmTBI) are often limited to impacts in the single digits. Herein, we describe the effects of 30 rmTBIs, examining structural and pathological changes in mice up to 365 days after injury. We found that single mTBI causes a brief loss of consciousness and a transient reduction in dendritic spines, reflecting a loss of excitatory synapses. Single mTBI does not cause axonal injury, neuroinflammation, or cell death in the gray or white matter. Thirty rmTBIs with a 1-day interval between each mTBI do not cause dendritic spine loss; however, when the interinjury interval is increased to 7 days, dendritic spine loss is reinstated. Thirty rmTBIs cause white matter pathology characterized by positive silver and Fluoro Jade B staining, and microglial proliferation and activation. This pathology continues to develop through 60 days, and is still apparent at 365 days, after injury. However, rmTBIs did not increase beta-amyloid levels or tau phosphorylation in the 3xTg-AD mouse model of Alzheimer disease. Our data reveal that single mTBI causes a transient loss of synapses, but that rmTBIs habituate to repetitive injury within a short time period. rmTBI causes the development of progressive white matter pathology that continues for months after the final impact. PMID- 26857509 TI - Smoking and Passive Smoke Exposure Among Adolescents in Germany. AB - BACKGROUND: Children and adolescents are the most important target group for smoking prevention and non-smoker protection measures (smoke-free legislation). In this article, we discuss trends over time and differences between social groups with regard to smoking and passive smoke exposure among adolescents in Germany. METHODS: The data evaluated in this article were collected in two different study periods of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), namely, 2003-2006 and 2009-2012. Adolescents aged 11 to 17 were asked about their smoking behavior and passive smoke exposure (6812 and 5258 respondents in the two study periods, respectively). Their social status was rated with an index based on information supplied by the adolescents' parents about their level of education, occupation, and income. RESULTS: The prevalence of smoking among adolescents fell in approximately six years from 20.4% to 12.0% (p< 0.001), and that of daily smoking from 13.3% to 5.4% (p<0.001). The percentage of non-smokers who spent time several days per week, or every day, in rooms where other persons were smoking declined from 35.1% to 18.8% (p<0.001). The lower the respondents' social status, the more likely they were to smoke daily and to have regular passive exposure to smoking. CONCLUSION: The findings suggest that the measures implemented in recent years to protect adolescents from the health risks of active and passive smoking have been beneficial independently of the adolescents' social backgrounds. PMID- 26857511 TI - Erratum. PMID- 26857510 TI - Atraumatic Femoral Head Necrosis in Adults. AB - BACKGROUND: Atraumatic necrosis of the femoral head is a common cause of hip arthrosis in middle age. In Germany, it affects 5000-7000 patients per year, corresponding to an incidence of 0.01%. Though rarer than primary hip arthrosis, it is still of major clinical and socio-economic significance. Patients with this problem should be diagnosed early and given stage-appropriate treatment. METHODS: This review is based on pertinent publications that were retrieved by a selective search in the PubMed, Embase, Medline, and Cochrane Library databases using the terms "osteonecrosis," "femoral head necrosis," "diagnosis," "classification," "conservative treatment," "surgical treatment," "joint preservation," "osteotomy," and "arthroplasty," as well as a recent guideline on atraumatic necrosis of the femoral head in adults. RESULTS: The etiology and pathogenesis of atraumatic femoral head necrosis in adults are not yet fully clear. The main risk factor is prolonged corticosteroid treatment. Nonspecific complaints and an initially normal plain x-ray of the hip can delay the diagnosis. The diagnosis is established by plain x-ray, computerized tomography, magnetic resonance tomography, and scintigraphy. Conservative treatment alone is not considered adequate. The range of surgical treatments includes joint-preserving and (for more severe necrosis) joint-resecting methods. CONCLUSION: Atraumatic femoral head necrosis in adults is a disease that progresses in stages; depending on its stage, it can either be cured or lead to hip arthrosis. A full cure is possible only in early stages. Current research focuses on the effect of new drugs on the intermediateand long-term outcome. PMID- 26857512 TI - Which Patients Will Benefit? PMID- 26857513 TI - The Renaissance of Digitoxin Is Overdue. PMID- 26857514 TI - Rapid Application Is Crucial. PMID- 26857515 TI - In Reply. PMID- 26857516 TI - Transungual Delivery of Ketoconazole Nanoemulgel for the Effective Management of Onychomycosis. AB - Ketoconazole (KCZ) nanoemulgel containing permeation enhancer was formulated as a vehicle for transungual drug delivery, and its efficacy to inhibit the growth of onychomycotic dermatophytes was investigated in vitro. Different components of oil-in-water nanoemulsions were moderately agitated by classical titration method and passed through a high-pressure homogenizer to formulate various nanoemulsions, which were further identified by constructing pseudo-ternary phase diagrams. Stress-stability testing was carried out for the nanoemulsions, and those that passed these tests were characterized for mean droplet size, zeta potential, morphology, pH, refractive index, viscosity and transmittance. Mean droplet size and zeta potential of the optimized nanoemulsion (NE3) were found to be 77.52 +/- 0.92 nm (polydispersity index (PDI) = 0.128 +/- 0.035) and -5.44 +/- 0.67 mV, respectively. Optimized nanoemulsion was converted into nanoemulgel (NEG1) with 1% (w/w) of gelling agent (Carbopol(r) Ultrez 21) and 1%-2% (v/v) thioglycolic acid as permeation enhancer, and evaluated for pH, viscosity, spreadability, extrudability, tensile strength and bio-adhesion measurement. In vitro cumulative drug released at the end of 24 h from NE3, NEG1 and drug suspension were found to be 98.87 +/- 1.29, 84.42 +/- 2.78% and 54.86 +/- 2.19%, respectively. Ex vivo transungual permeation values for KCZ through goat hooves from NE3, NEG1 and drug suspension were found to be 62.49 +/- 2.98, 77.54 +/- 2.88% and 38.54 +/- 2.54%, respectively, in 24 h. The antifungal effect of NEG1 on Trichophyton rubrum and Candida albicans showed a significant (p < 0.05) zone of inhibition as compared to drug solution. Skin irritation and histopathology studies on rat skin showed the safe topical use and enhanced permeation of formulated nanoemulgel. PMID- 26857518 TI - Electromyographic evaluation of countermeasures during the terrestrial simulation of interplanetary spaceflight in Mars500 project. AB - The efficiency of six countermeasures (CM) for muscle atrophy was compared over 520 days of confinement during the terrestrial simulation of round space flight to Mars using surface electromyography (sEMG). Three of CM were cyclic exercises (a motor-driven and leg-driven treadmill, cycle ergometer), resistive exercises (the multifunctional dynamometer for space-MDS, and expanders), and vibration platform. Each of CM was applied for each crew member (n=6) once over the experiment, for 70 days in a row, in prescribed order. sEMG was collected during the "force step test" in which the subject voluntarily produced pressure by lower limb, with minimal force increment. The mean frequency (MNF) and average amplitude of sEMG were analyzed. The MNF of sEMG decreased from 104.3+/-4.2 to 95.3+/-2.9Hz (P<0.05) in the soleus muscle after 70 days of exercising on the leg driven treadmill and after 35 days-on vibration platform. It can be caused by earlier (10-250ms) recruitment of the soleus in respect with the medial gastronemius on the leg-driven treadmill, while on the motor-driven treadmill synergists activated synchronously. In other lower leg muscles, MNF decreased from 180 to 200 to 165-180Hz after 70 days of resistive exercises on the MDS device. CM caused no effect on sEMG amplitude. In conclusion, (1) the leg-driven treadmill, the MDS and vibration platform significantly depressed MNF of sEMG of lower extremity muscles; (2) the leg-driven treadmill and vibration platform specifically affected the soleus muscle. Therefore, these CM can be recommended for a more extensive use on ISS board. PMID- 26857517 TI - Monitor design with multiple self-loops for maximally permissive supervisors. AB - In this paper, we improve the previous work by considering that a control place can have multiple self-loops. Then, two integer linear programming problems (ILPPs) are formulated. Based on the first ILPP, an iterative deadlock control policy is developed, where a control place is computed at each iteration to implement as many marking/transition separation instances (MTSIs) as possible. The second ILPP can find a set of control places to implement all MTSIs and the objective function is used to minimize the number of control places. It is a non iterative deadlock control strategy since we need to solve the ILPP only once. Both ILPPs can make all legal markings reachable in the controlled system, i.e., the obtained supervisor is behaviorally optimal. Finally, we provide examples to illustrate the proposed approaches. PMID- 26857519 TI - Death and dignity in Catholic Christian thought. AB - This article traces the history of the concept of dignity in Western thought, arguing that it became a formal Catholic theological concept only in the late nineteenth century. Three uses of the word are distinguished: intrinsic, attributed, and inflorescent dignity, of which, it is argued, the intrinsic conception is foundational. The moral norms associated with respect for intrinsic dignity are discussed briefly. The scriptural and theological bases for adopting the concept of dignity as a Christian idea are elucidated. The article concludes by discussing the relevance of this concept of dignity to the spiritual and ethical care of the dying. PMID- 26857520 TI - In Memoriam: Charles Kennedy (August 27, 1920, to October 6, 2015). PMID- 26857521 TI - Oral Prednisolone Versus Intramuscular Corticotropin in West Syndrome. PMID- 26857523 TI - Myotonic Dystrophy Type 1: A Neurological Cause of Dysphagia. PMID- 26857522 TI - Maternal Infections During Pregnancy and Cerebral Palsy in the Child. AB - BACKGROUND: Chorioamnionitis is a risk factor for cerebral palsy. The relationship between extra-amniotic infections and cerebral palsy is less well studied. We examined maternal intra-amniotic and extra-amniotic infections and risk of cerebral palsy in the child. METHODS: Among a retrospective cohort of 6 million Californian births, 1991-2001, we analyzed administrative maternal and newborn hospital discharge abstracts linked to records of all children receiving services for cerebral palsy at the California Department of Developmental Services. We identified maternal hospital diagnoses of intra-amniotic (chorioamnionitis) and extra-amniotic (other genitourinary and respiratory) infections occurring up to 12 months before delivery. Using multivariable logistic regression, we determined the independent association between maternal infections and cerebral palsy, adjusting for infant sex, maternal age, race, education, socioeconomic status, and obesity. RESULTS: About 5.5% of mothers had a hospital discharge diagnosis of at least one of the following: chorioamnionitis (2.0%), other genitourinary (3.1%), and respiratory infection (0.6%). An infection diagnosis was more common in mothers of the 8473 infants with cerebral palsy than in mothers of unaffected children (13.7% vs 5.5%, P < 0.001). All three types of maternal infections (chorioamnionitis, odds ratio [OR] 3.1, 95% confidence interval [CI] 2.9-3.4; other genitourinary infection, OR 1.4, 95% CI 1.3-1.6; and respiratory infection, OR 1.9, 95% CI 1.5-2.2) were associated with cerebral palsy in multivariable analyses. Maternal extra-amniotic infections, whether diagnosed during prenatal or birth hospitalizations, conferred an increased risk of cerebral palsy. CONCLUSIONS: Maternal extra-amniotic infections diagnosed in the hospital during pregnancy are associated with a modestly increased risk of cerebral palsy in the child. PMID- 26857524 TI - Comparative Effectiveness of Imaging Modalities for the Diagnosis of Intestinal Obstruction in Neonates and Infants:: A Critically Appraised Topic. AB - RATIONALE AND OBJECTIVES: The purpose of this study was to critically appraise and compare the diagnostic performance of imaging modalities that are used for the diagnosis of upper and lower gastrointestinal (GI) tract obstruction in neonates and infants. METHODS: A focused clinical question was constructed and the literature was searched using the patient, intervention, comparison, outcome method comparing radiography, upper GI contrast study, and ultrasound in the detection of upper GI tract obstruction such as duodenal atresia and stenosis, jejunal and ileal atresia, and malrotation and volvulus. The same methods were used to compare radiography and contrast enema in the detection of lower GI tract obstruction such as meconium plug syndrome, meconium ileus, Hirschsprung disease, and imperforate anus. Retrieved articles were appraised and assigned a level of evidence based on the Oxford University Centre for Evidence-Based Medicine hierarchy of validity for diagnostic studies. RESULTS: There were no sensitivities/specificities available for the imaging diagnosis of duodenal atresia or stenosis, jejunal or ileal atresias, meconium plug, and meconium ileus or for the use of cross-table lateral radiography for the diagnosis of rectal pouch distance from skin in imperforate anus. The retrieved sensitivity for the detection of malrotation on upper GI contrast study is 96%, and the sensitivity for the diagnosis of midgut volvulus on upper GI contrast study is 79%. The retrieved sensitivity and specificity for the detection of malrotation with volvulus on ultrasound were 89% and 92%, respectively. The retrieved sensitivity and specificity for the detection of Hirschsprung disease on contrast enema were 70% and 83%, respectively. The retrieved sensitivity of invertogram for the diagnosis of rectal pouch distance from skin in imperforate anus is 27%. The retrieved sensitivities of perineal ultrasound and colostography for the diagnosis of rectal pouch distance from skin in imperforate anus were 86% and 100%, respectively. CONCLUSIONS: There is limited evidence for the imaging diagnosis of duodenal atresia and stenosis, jejunal and ileal atresias, meconium plug, meconium ileus, and imperforate anus, with recommended practice based mainly on low-quality evidence or expert opinion. The available evidence supports the use of upper GI contrast study for the diagnosis of malrotation and volvulus, with ultrasound as an adjunct to diagnosis. Contrast enema is useful in the investigation of suspected Hirschsprung disease, but a negative study does not outrule the condition. Colostography is the investigation of choice for the work up of infants with complex anorectal malformations before definitive surgical repair. PMID- 26857525 TI - Retrospective analysis of "new" flame retardants in the global atmosphere under the GAPS Network. AB - A retrospective analysis was conducted on air samples that were collected in 2005 under the Global Atmospheric Passive Sampling (GAPS) Network around the time period when the Stockholm Convention on Persistent Organic Pollutants came into force. Results are presented for several new flame retardants, including hexabromocyclododecane (HBCD), which was recently listed under the Convention (2013). These results represent the first global-scale distributions in air for these compounds. The targeted compounds are shown to have unique global distributions in air, which highlights the challenges in understanding the sources and environmental fate of each chemical, and ultimately in their assessments as persistent organic pollutants. The study also demonstrates the feasibility of using the PUF disk passive air sampler to study these new flame retardants in air, many of which exist entirely in the particle-phase as demonstrated in this study using a KOA-based partitioning model. PMID- 26857526 TI - Design of a Novel Composite H2 S-Releasing Hydrogel for Cardiac Tissue Repair. AB - The design of 3D scaffolds is a crucial step in the field of regenerative medicine. Scaffolds should be degradable and bioresorbable as well as display good porosity, interconnecting pores, and topographic features; these properties favour tissue integration and vascularization. These requirements could be fulfilled by hybrid hydrogels using a combination of natural and synthetic components. Here, the mechanical and biological properties of a polyethylene glycol-fibrinogen hydrogel (PFHy) are improved in order to favour the proliferation and differentiation of human Sca-1(pos) cardiac progenitor cells (hCPCs). PFHys are modified by embedding air- or perfluorohexane-filled bovine serum albumin microbubbles (MBs) and characterized. Changes in cell morphology are observed in MBs-PFHys, suggesting that MBs could enhance the formation of bundles of cells and influence the direction of the spindle growth. The properties of MBs as carriers of active macromolecules are also exploited. For the first time, enzyme-coated MBs have been used as systems for the production of hydrogen sulfide (H2 S)-releasing scaffolds. Novel H2 S-releasing PFHys are produced, which are able to improve the growth of hCPCs. This novel 3D cell scaffold system will allow the assessment of the effects of H2 S on the cardiac muscle regeneration with its potential applications in tissue repair. PMID- 26857528 TI - Potential Role for YB-1 in Castration-Resistant Prostate Cancer and Resistance to Enzalutamide Through the Androgen Receptor V7. AB - BACKGROUND: Although androgen deprivation therapy for advanced prostate cancer initially exerts excellent anticancer effects, most prostate cancer treated with androgen deprivation therapy eventually recurs as castration-resistant prostate cancer (CRPC). Although aberrant kinase activation has been proposed as a mechanism of castration resistance, comprehensive kinase profiles in CRPC remain unknown. Therefore, we aimed to elucidate the kinome in CRPC as well as the role of key molecules. METHODS: We utilized a kinome array in androgen-dependent LNCaP and castration-resistant CxR cells. The effect of Y-box binding protein-1 (YB-1) on androgen receptor (AR) expression was examined by quantitative polymerase chain reaction and western blot analysis. The association between polymorphisms in the YB-1 gene determined by genotyping and YB-1 expression evaluated by immunohistochemistry in prostate cancer tissues, as well as outcome in metastatic prostate cancer, were investigated by the Cochran-Armitage test and the Cox proportional hazards model, respectively. All statistical tests were two-sided. RESULTS: One hundred fifty-six of 180 kinase phosphorylation sites, including ERK and RSK, were activated in CRPC cells, leading to increased phosphorylation of YB 1, which is a key molecule in the progression to CRPC. YB-1 signaling regulated AR V7 expression, and YB-1 inhibition augmented the anticancer effect of enzalutamide. Moreover, polymorphism (rs12030724) in the YB-1 gene affected YB-1 expression in 93 prostate cancer tissues (YB-1 positive rate; 14.3% in TT, 40.0% in AT, and 52.9% in AA, P = .04) and associated with probability of progression in 104 metastatic prostate cancer case patients (AT/TT vs AA, hazard ratio = 0.49, 95% confidence interval = 0.32 to 0.77, P = .001). CONCLUSIONS: YB-1 appears to be a promising target to inhibit the development of castration resistance, even at the AR variant-expressing stage. Polymorphism in the YB-1 gene may be a promising predictive biomarker in hormonal therapy. PMID- 26857529 TI - Impact of mutations in DNA gyrase genes on quinolone resistance in Campylobacter jejuni. AB - Amino acid substitutions providing quinolone resistance to Campyloabcter jejuni have been found in the quinolone resistance-determining region of protein DNA gyrase subunit A (GyrA), with the highest frequency at position 86 followed by position 90. In this study, wild-type and mutant recombinant DNA gyrase subunits were expressed in Escherichia coli and purified using Ni-NTA agarose column chromatography. Soluble 97 kDa GyrA and 87 kDa DNA gyrase subunit B were shown to reconstitute ATP-dependent DNA supercoiling activity. A quinolone-inhibited supercoiling assay demonstrated the roles of Thr86Ile, Thr86Ala, Thr86Lys, Asp90Asn, and Asp90Tyr amino acid substitutions in reducing sensitivity to quinolones. The marked effect of Thr86Ile on all examined quinolones suggested the advantage of this substitution in concordance with recurring isolation of quinolone-resistant C. jejuni. An analysis of the structure-activity relationship showed the importance of the substituent at position 8 in quinolones to overcome the effect of Thr86Ile. Sitafloxacin (SIT), which has a fluorinate cyclopropyl ring at R-1 and a chloride substituent at R-8, a characteristic not found in other quinolones, showed the highest inhibitory activity against all mutant C. jejuni gyrases including ciprofloxacin-resistant mutants. The results suggest SIT as a promising drug for the treatment of campylobacteriosis caused by CIP resistant C. jejuni. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26857527 TI - Association of Interferon Regulatory Factor-4 Polymorphism rs12203592 With Divergent Melanoma Pathways. AB - BACKGROUND: Solar elastosis and neval remnants are histologic markers characteristic of divergent melanoma pathways linked to differences in age at onset, host phenotype, and sun exposure. However, the association between these pathway markers and newly identified low-penetrance melanoma susceptibility loci remains unknown. METHODS: In the Genes, Environment and Melanoma (GEM) Study, 2103 Caucasian participants had first primary melanomas that underwent centralized pathology review. For 47 single-nucleotide polymorphisms (SNPs) previously identified as low-penetrant melanoma risk variants, we used multinomial logistic regression to compare melanoma with solar elastosis and melanoma with neval remnants simultaneously to melanoma with neither of these markers, excluding melanomas with both markers. All statistical tests were two sided. RESULTS: IRF4 rs12203592 was the only SNP to pass the false discovery threshold in baseline models adjusted for age, sex, and study center. rs12203592*T was associated positively with melanoma with solar elastosis (odds ratio [OR] = 1.47, 95% confidence interval [CI] = 1.18 to 1.82) and inversely with melanoma with neval remnants (OR = 0.65, 95% CI = 0.48 to 0.87) compared with melanoma with neither marker (P global = 3.78 x 10(-08)). Adjusting for phenotypic characteristics and total sun exposure hours did not materially affect rs12203592's associations. Distinct early- and late-onset age distributions were observed in patients with IRF4 rs12203592 [CC] and [TT] genotypes, respectively. CONCLUSIONS: Our findings suggest a role of IRF4 rs12203592 in pathway-specific risk for melanoma development. We hypothesize that IRF4 rs12203592 could underlie in part the bimodal age distribution reported for melanoma and linked to the divergent pathways. PMID- 26857530 TI - Impact of Mode of Delivery on Female Postpartum Sexual Functioning: Spontaneous Vaginal Delivery and Operative Vaginal Delivery vs. Cesarean Section. AB - INTRODUCTION: Several studies have explored the association between modes of delivery and postpartum female sexual functioning, although with inconsistent findings. AIM: To investigate the impact of mode of delivery on female postpartum sexual functioning by comparing spontaneous vaginal delivery, operative vaginal delivery, and cesarean section. METHODS: One hundred thirty-two primiparous women who had a spontaneous vaginal delivery, 45 who had an operative vaginal delivery, and 92 who underwent a cesarean section were included in the study (N = 269). Postpartum sexual functioning was evaluated 6 months after childbirth using the Female Sexual Function Index. Time to resumption of sexual intercourse, postpartum depression, and current breastfeeding also were assessed 6 months after delivery. MAIN OUTCOME MEASURES: Female Sexual Function Index total and domain scores and time to resumption of sexual intercourse at 6 months after childbirth. RESULTS: Women who underwent an operative vaginal delivery had poorer scores on arousal, lubrication, orgasm, and global sexual functioning compared with the cesarean section group and lower orgasm scores compared with the spontaneous vaginal delivery group (P < .05). The mode of delivery did not significantly affect time to resumption of sexual intercourse. Women who were currently breastfeeding had lower lubrication, more pain at intercourse, and longer time to resumption of sexual activity. CONCLUSION: Operative vaginal delivery might be associated with poorer sexual functioning, but no conclusions can be drawn from this study regarding the impact of pelvic floor trauma (perineal laceration or episiotomy) on sexual functioning because of the high rate of episiotomies. Overall, obstetric algorithms currently in use should be refined to decrease further the risk of operative vaginal delivery. PMID- 26857532 TI - Reflections on a Pain Medicine Pioneer: Carey Stratton Hill, Jr., M.D. (1928 2015): Professor Emeritus of Medicine, The University of Texas M.D. Anderson Cancer Center. PMID- 26857531 TI - Modeling of Salmonella Contamination in the Pig Slaughterhouse. AB - In this article we present a model for Salmonella contamination of pig carcasses in the slaughterhouse. This model forms part of a larger QMRA (quantitative microbial risk assessment) on Salmonella in slaughter and breeder pigs, which uses a generic model framework that can be parameterized for European member states, to describe the entire chain from farm-to-consumption and the resultant human illness. We focus on model construction, giving mathematical formulae to describe Salmonella concentrations on individual pigs and slaughter equipment at different stages of the slaughter process. Variability among individual pigs and over slaughterhouses is incorporated using statistical distributions, and simulated by Monte Carlo iteration. We present the results over the various slaughter stages and show that such a framework is especially suitable to investigate the effect of various interventions. In this article we present the results of the slaughterhouse module for two case study member states. The model outcome represents an increase in average prevalence of Salmonella contamination and Salmonella numbers at dehairing and a decrease of Salmonella numbers at scalding. These results show good agreement when compared to several other QMRAs and microbiological studies. PMID- 26857533 TI - Clear cell papillary renal cell carcinoma as part of histologically discordant multifocal renal cell carcinoma: A case report and review of literature. AB - BACKGROUND: Multifocal renal cell carcinoma of different histological subtypes within a single kidney is rare. We report a recently classified clear cell (tubulo) papillary renal cell carcinoma as part of an unusual case of multifocal renal cell carcinoma of discordant histological subtypes. RESULTS: A 57 year-old man was found to have multiple renal tumors and cysts on imaging and underwent a laparoscopic left radical nephrectomy. Pathological review showed multifocal renal cell carcinoma (clear cell (tubulo) papillary, clear cell and papillary renal cell carcinomas and papillary adenomas). Morphology of clear cell papillary renal cell carcinoma was supported by immunohistochemical profile (CK7+, HMWK+, CAIX+, AMACR-, CD10-, TFE3-). CONCLUSIONS: This is the first report of clear cell papillary renal cell carcinoma as part of multifocal renal cell carcinoma of different histological subtypes. Related lineage of clear cell renal cell carcinoma and papillary renal cell carcinoma is supported by the highest prevalence of their combination within multifocal renal cell carcinoma of different histological subtypes along with their molecular interconnection. Clear cell papillary renal cell carcinoma may be uniquely placed between clear cell and papillary renal cell carcinomas since it shows morphological features intermediate between clear cell and papillary renal cell carcinoma along with overlapping but unique immunohistochemical profile. Clear cell papillary renal cell carcinoma may be molecularly related to clear cell and papillary renal cell carcinomas since the tumors overexpress markers of HIF pathway activation with normal/elevated VHL mRNA expression and some tumors show losses of chromosome 3. Due to the overlapping morphology, it is possible that cases of clear cell papillary renal cell carcinoma may have been misclassified as papillary or clear cell renal cell carcinoma in the literature, incorrectly increasing their reported prevalence. Identification of multifocal RCCs may be related to the extent of pathological sampling. PMID- 26857534 TI - Breast cancer stem cells phenotype and plasma cell-predominant breast cancer independently indicate poor survival. AB - PURPOSE: Cancer stem cell-tumor microenvironment ecosystem is proposed to drive tumor heterogeneity. Tumor-infiltrating lymphocytes (TILs) in breast cancer ecosystem were demonstrated to indicate better prognosis and benefit from chemotherapy. This study sought to detect the association between breast cancer stem cells and TILs. METHODS: 92 patients with breast cancer were enrolled. Matched cancerous and paracancerous tissues were assembled in a tissue microarray and immunohistochemistry was employed to test expression of breast cancer stem cells (BCSCs) markers. TILs counts were estimated with global hematoxylin-eosin staining. The association between TILs and BCSCs phenotypes was analysed by multivariate analysis. RESULTS: Although it was unable to find direct significant association between BCSCs phenotypes and TILs, the BCSCs phenotype with CD44(+)CD24(-)ALDH1A1(+)EpCAM(+)CD49f(+) was proved to be associated with worse DFS and OS (P=0.037 and 0.001). This result was confirmed by cox proportional hazards regression model (for DFS and OS respectively, HR=2.438 and 3.383, P=0.019 [95%CI 1.418-3.457] and 0.025 [95%CI 1.162-9.843]). Additionally, in results of TILs, plasma cell-predominant breast cancer (PPBC) was unexpectedly found to indicate worse OS and HR was 2.686 (P=0.038 [95%CI 1.582-3.789]). CONCLUSIONS: The BCSCs phenotype and PPBC may be helpful stratified factors in future clinical trials. The underlying mechanism needs further research. PMID- 26857535 TI - Branched-chain amino acid-enriched nutrient increases blood platelet count in patients after endoscopic injection sclerotherapy. AB - AIM: Protein and energy malnutrition is a severe problem for patients with liver cirrhosis (LC) and fasting often induces starvation which is a vitally important outcome. Dietary restriction is essential for endoscopic injection sclerotherapy (EIS) in patients with risky esophageal varices, thereby creating the possible exacerbation of nutritional state and inducing liver dysfunction. Whether EIS induces nutritional deficiency in LC patients and the effects of branched-chain amino acid (BCAA)-enriched nutrient are prospectively investigated. METHODS: A total of 61 LC patients were randomly divided into an EIS monotherapy group (non BCAA group, n = 31) and an EIS combined with BCAA therapy group (n = 30). Platelet count, blood chemistry and somatometry values were prospectively measured at five time points. RESULTS: The platelet counts before treatment were at the same level in both groups (P = 0.72). Three months after treatment, the counts decreased in the non-BCAA group; however, they increased in the BCAA group (P = 0.019). Body mass index, triceps skin fold thickness and arm muscle circumference significantly decreased in both groups. The BCAA and tyrosine ratio value increased only in the BCAA group (P < 0.01). The skeletal muscle volume measured by InBody720 significantly decreased in the non-BCAA group (P < 0.001). CONCLUSION: EIS induced protein-energy malnutrition, however, skeletal muscle volume was maintained by taking BCAA. Administration of BCAA had some effect in maintaining the nutritional state, and may improve the platelet count. Taking a greater amount of nutrients and shorter dietary restriction period or hospitalization was desirable. PMID- 26857537 TI - An Additive Definition of Molecular Complexity. AB - A framework for molecular complexity is established that is based on information theory and consistent with chemical knowledge. The resulting complexity index Cm is derived from abstracting the information content of a molecule by the degrees of freedom in the microenvironments on a per-atom basis, allowing the molecular complexity to be calculated in a simple and additive way. This index allows the complexity of any molecule to be universally assessed and is sensitive to stereochemistry, heteroatoms, and symmetry. The performance of this complexity index is evaluated and compared against the current state of the art. Its additive character gives consistent values also for very large molecules and supports direct comparisons of chemical reactions. Finally, this approach may provide a useful tool for medicinal chemistry in drug design and lead selection, as demonstrated by correlating molecular complexities of antibiotics with compound-specific parameters. PMID- 26857538 TI - Skeletal muscle regeneration in cancer cachexia. AB - Muscle wasting is the most important phenotypic and clinical feature of cancer cachexia, and the principal cause of impaired physical function, fatigue, and respiratory complications. Muscle loss has been attributed to a variable combination of reduced nutritional intake and an imbalance between anabolic and catabolic processes. It has been suggested that defective skeletal muscle regeneration may also contribute to muscle wasting in cancer patients. However, there is little in vitro or in vivo data available, in either animals or in humans, regarding skeletal muscle regeneration in cancer wasting. The aim of the present review is to define the role of skeletal muscle regeneration in the muscle wasting of cancer patients and to determine possible therapeutic implications. PMID- 26857539 TI - Feasibility, efficacy, and safety of ultrasound-guided axillary plexus blockade in pediatric patients with epidermolysis bullosa dystrophica. AB - BACKGROUND: In patients suffering from epidermolysis bullosa dystrophica (DEB), the most severe form of epidermolysis bullosa, trauma or friction cause separation of the skin from underlying tissue with consecutive painful blisters, scarifications, contractures, and pseudosyndactyly. To retain functionality of the hands surgical procedures are necessary. Anesthesia is challenging as difficult airways make general anesthesia risky. Regional anesthesia is considered controversial in patients with EB as accidental subcutaneous injections can cause severe blisters. As ultrasound-guided procedures became standard of care this might have changed however. AIM: In this case series, we describe feasibility, efficacy, and safety of ultrasound-guided plexus axillaris block in DEB patients undergoing hand surgery. METHOD: We performed a retrospective analysis of the charts of all children with DEB undergoing hand surgery under plexus axillaris block and sedation between 2009 and 2013 in our institution. RESULTS: Nineteen procedures in nine children were performed. Induction of anesthesia (securing monitoring, sedation, plexus block) took a mean time of 34 min. Perioperative analgesia was adequate in all procedures. No complications such as airway incidents, conversion to general anesthesia, movement during surgery, incomplete block, or formation of new blisters were seen. CONCLUSION: Ultrasound-guided plexus axillaris block in DEB patients undergoing hand surgery in our institution has been feasible, effective, and safe. PMID- 26857540 TI - Coronary Sinus Orifice Atresia Associated with Persistent Left Superior Vena Cava: A Case Report with Literature Review. AB - Coronary sinus (CS) orifice atresia is a rare malformation, usually associated with persistent left superior vena cava (PLSVC). The preoperative diagnosis is very challenging. The only clue for diagnosis is the reverse direction of flow through PLSVC. We present the case of a 69-year-old woman with CS orifice atresia and PLSVC. Then, we retrospectively study 99 cases of this malformation, including ours. This malformation is usually associated with the "enlarged" CS (>12 mm) and "small" PLSVC (<=5 mm), with the incidence of 81 and 87%, respectively, from the literature review. PMID- 26857536 TI - Reactive oxygen/nitrogen species and contractile function in skeletal muscle during fatigue and recovery. AB - The production of reactive oxygen/nitrogen species (ROS/RNS) is generally considered to increase during physical exercise. Nevertheless, direct measurements of ROS/RNS often show modest increases in ROS/RNS in muscle fibres even during intensive fatiguing stimulation, and the major source(s) of ROS/RNS during exercise is still being debated. In rested muscle fibres, mild and acute exposure to exogenous ROS/RNS generally increases myofibrillar submaximal force, whereas stronger or prolonged exposure has the opposite effect. Endogenous production of ROS/RNS seems to preferentially decrease submaximal force and positive effects of antioxidants are mainly observed during fatigue induced by submaximal contractions. Fatigued muscle fibres frequently enter a prolonged state of reduced submaximal force, which is caused by a ROS/RNS-dependent decrease in sarcoplasmic reticulum Ca(2+) release and/or myofibrillar Ca(2+) sensitivity. Increased ROS/RNS production during exercise can also be beneficial and recent human and animal studies show that antioxidant supplementation can hamper the beneficial effects of endurance training. In conclusion, increased ROS/RNS production have both beneficial and detrimental effects on skeletal muscle function and the outcome depends on a combination of factors: the type of ROS/RNS; the magnitude, duration and location of ROS/RNS production; and the defence systems, including both endogenous and exogenous antioxidants. PMID- 26857541 TI - PPAR Agonists: II. Fenofibrate and Tesaglitazar Alter Behaviors Related to Voluntary Alcohol Consumption. AB - BACKGROUND: In the accompanying article, we showed that activation of peroxisome proliferator-activated receptor alpha (PPARalpha) signaling by fenofibrate and tesaglitazar decreases ethanol (EtOH) consumption in mice. In this study, we determined the role of these PPAR agonists in EtOH-related behaviors and other actions that may be important in regulating EtOH consumption. METHODS: The effects of fenofibrate (150 mg/kg) and tesaglitazar (1.5 mg/kg) were examined on the following responses in male and female C57BL/6J (B6) and B6 * 129S4 mice: preference for saccharin, EtOH-induced conditioned place preference (CPP), conditioned taste aversion (CTA), loss of righting reflex, and withdrawal, acoustic startle reflex, response to novelty, and EtOH clearance. Because the B6 inbred strain usually displays weak EtOH-induced CPP and weak EtOH-induced acute withdrawal, B6 * 129S4 mice were also studied. RESULTS: Fenofibrate and tesaglitazar decreased the novelty response and increased acute EtOH withdrawal severity, and fenofibrate increased EtOH-induced CTA. Two important factors for EtOH consumption (saccharin preference and EtOH-induced CPP) were not altered by fenofibrate or tesaglitazar. EtOH clearance was increased by both fenofibrate and tesaglitazar. Response to novelty, acute withdrawal, and EtOH clearance show sex differences and could contribute to the reduced EtOH consumption following fenofibrate administration. CONCLUSIONS: These studies indicate the complexity of EtOH-dependent and EtOH-independent behaviors that are altered by PPAR agonists and provide evidence for novel behavioral actions of these drugs that may contribute to PPAR-mediated effects on alcohol drinking. PMID- 26857543 TI - Listening to both sides: A qualitative comparison between patients with hepatitis C and their healthcare professionals' perceptions of the facilitators and barriers to hepatitis C treatment adherence and completion. AB - This qualitative study compares and contrasts the perspectives of healthcare professionals who treat hepatitis C with those of patients in treatment. Comparative analysis of semi-structured interviews with 20 healthcare professionals and 20 patients undergoing treatment for hepatitis C concluded that patients and healthcare professionals disagreed on the source of communication breakdowns, but both felt that individualised clinical information improved adherence. Stigma was recognised as a barrier to treatment adherence by both patients and healthcare professionals. Limitations of the healthcare system, such as patients receiving inconsistent information and long wait times, negatively impacted both patients and providers. PMID- 26857542 TI - Structure prediction using sparse simulated NOE restraints with Rosetta in CASP11. AB - In CASP11 we generated protein structure models using simulated ambiguous and unambiguous nuclear Overhauser effect (NOE) restraints with a two stage protocol. Low resolution models were generated guided by the unambiguous restraints using continuous chain folding for alpha and alpha-beta proteins, and iterative annealing for all beta proteins to take advantage of the strand pairing information implicit in the restraints. The Rosetta fragment/model hybridization protocol was then used to recombine and regularize these models, and refine them in the Rosetta full atom energy function guided by both the unambiguous and the ambiguous restraints. Fifteen out of 19 targets were modeled with GDT-TS quality scores greater than 60 for Model 1, significantly improving upon the non-assisted predictions. Our results suggest that atomic level accuracy is achievable using sparse NOE data when there is at least one correctly assigned NOE for every residue. Proteins 2016; 84(Suppl 1):181-188. (c) 2016 Wiley Periodicals, Inc. PMID- 26857544 TI - Expression of multiple Bacillus subtilis genes is controlled by decay of slrA mRNA from Rho-dependent 3' ends. AB - Timely turnover of RNA is an important element in the control of bacterial gene expression, but relatively few specific targets of RNA turnover regulation are known. Deletion of the Bacillus subtilis pnpA gene, encoding the major 3' exonuclease turnover enzyme, polynucleotide phosphorylase (PNPase), was shown previously to cause a motility defect correlated with a reduced level of the 32 gene fla/che flagellar biosynthesis operon transcript.fla/che operon transcript abundance has been shown to be inhibited by an excess of the small regulatory protein, SlrA, and here we find that slrA mRNA accumulated in the pnpA-deletion mutant. Mutation of slrA was epistatic to mutation of pnpA for the motility related phenotype. Further, Rho-dependent termination was required for PNPase turnover of slrA mRNA. When the slrA gene was provided with a Rho-independent transcription terminator, gene regulation was no longer PNPase-dependent. Thus we show that the slrA transcript is a direct target of PNPase and that regulation of RNA turnover is a major determinant of motility gene expression. The interplay of specific transcription termination and mRNA decay mechanisms suggests selection for fine-tuning of gene expression. PMID- 26857545 TI - Telomere-binding protein regulates the chromosome ends through the interaction with histone deacetylases in Arabidopsis thaliana. AB - Telomeres are nucleoprotein complexes at the end of eukaryotic chromosomes. Many telomere-binding proteins bind to telomeric repeat sequences and further generate T-loops in animals. However, it is not clear if they regulate telomere organization using epigenetic mechanisms and how the epigenetic molecules are involved in regulating the telomeres. Here, we show direct interactions between the telomere-binding protein, AtTRB2 and histone deacetylases, HDT4 and HDA6, in vitro and in vivo AtTRB2 mediates the associations of HDT4 and HDA6 with telomeric repeats. Telomere elongation is found in AtTRB2, HDT4 and HDA6 mutants over generations, but also in met1 and cmt3 DNA methyltransferases mutants. We also characterized HDT4 as an Arabidopsis H3K27 histone deacetylase. HDT4 binds to acetylated peptides at residue K27 of histone H3 in vitro, and deacetylates this residue in vivo Our results suggest that AtTRB2 also has a role in the regulation of telomeric chromatin as a possible scaffold protein for recruiting the epigenetic regulators in Arabidopsis, in addition to its telomere binding and length regulation activity. Our data provide evidences that epigenetic molecules associate with telomeres by direct physical interaction with telomere-binding proteins and further regulate homeostasis of telomeres in Arabidopsis thaliana. PMID- 26857546 TI - Molecular sled sequences are common in mammalian proteins. AB - Recent work revealed a new class of molecular machines called molecular sleds, which are small basic molecules that bind and slide along DNA with the ability to carry cargo along DNA. Here, we performed biochemical and single-molecule flow stretching assays to investigate the basis of sliding activity in molecular sleds. In particular, we identified the functional core of pVIc, the first molecular sled characterized; peptide functional groups that control sliding activity; and propose a model for the sliding activity of molecular sleds. We also observed widespread DNA binding and sliding activity among basic polypeptide sequences that implicate mammalian nuclear localization sequences and many cell penetrating peptides as molecular sleds. These basic protein motifs exhibit weak but physiologically relevant sequence-nonspecific DNA affinity. Our findings indicate that many mammalian proteins contain molecular sled sequences and suggest the possibility that substantial undiscovered sliding activity exists among nuclear mammalian proteins. PMID- 26857547 TI - Kinetic mechanism and fidelity of nick sealing by Escherichia coli NAD+-dependent DNA ligase (LigA). AB - Escherichia coli DNA ligase (EcoLigA) repairs 3'-OH/5'-PO4 nicks in duplex DNA via reaction of LigA with NAD(+) to form a covalent LigA-(lysyl-Nzeta)-AMP intermediate (step 1); transfer of AMP to the nick 5'-PO4 to form an AppDNA intermediate (step 2); and attack of the nick 3'-OH on AppDNA to form a 3'-5' phosphodiester (step 3). A distinctive feature of EcoLigA is its stimulation by ammonium ion. Here we used rapid mix-quench methods to analyze the kinetic mechanism of single-turnover nick sealing by EcoLigA-AMP. For substrates with correctly base-paired 3'-OH/5'-PO4 nicks, kstep2 was fast (6.8-27 s(-1)) and similar to kstep3 (8.3-42 s(-1)). Absent ammonium, kstep2 and kstep3 were 48-fold and 16-fold slower, respectively. EcoLigA was exquisitely sensitive to 3'-OH base mispairs and 3' N:abasic lesions, which elicited 1000- to >20000-fold decrements in kstep2. The exception was the non-canonical 3' A:oxoG configuration, which EcoLigA accepted as correctly paired for rapid sealing. These results underscore: (i) how EcoLigA requires proper positioning of the nick 3' nucleoside for catalysis of 5' adenylylation; and (ii) EcoLigA's potential to embed mutations during the repair of oxidative damage. EcoLigA was relatively tolerant of 5' phosphate base mispairs and 5' N:abasic lesions. PMID- 26857549 TI - Combined model of the EBMT score modified model and the HCT-CI improves the stratification of high-risk patients undergoing unmanipulated haploidentical blood and marrow transplantation. AB - Both European Group for blood and marrow transplantation risk score (EBMT score modified model) and hematopoietic cell transplantation comorbidity index (HCT-CI) are suitable for evaluating patients undergoing unmanipulated haploidentical blood and marrow transplantation (HBMT), while the predictive capacity of the combined model following haploidentical transplantation is still unknown. In this study, we calculated and validated 322 consecutive unmanipulated HBMT patients. Patients in groups with HCT-CI scores of 0 or 1-2 exhibited similar overall survival (OS), non-relapse mortality (NRM), and relapse rates, independent of their EBMT score modified model. In the group in which patients' HCT-CI scores were >=3, patients with high EBMT score modified model showed lower OS (p = 0.003) and higher NRM (p = 0.001) than did patients with low EBMT score. In conclusion, this combined model can be used to predict outcomes and may improve the stratification of high-risk patients following unmanipulated HBMT. PMID- 26857548 TI - Next-generation bis-locked nucleic acids with stacking linker and 2'-glycylamino LNA show enhanced DNA invasion into supercoiled duplexes. AB - Targeting and invading double-stranded DNA with synthetic oligonucleotides under physiological conditions remain a challenge. Bis-locked nucleic acids (bisLNAs) are clamp-forming oligonucleotides able to invade into supercoiled DNA via combined Hoogsteen and Watson-Crick binding. To improve the bisLNA design, we investigated its mechanism of binding. Our results suggest that bisLNAs bind via Hoogsteen-arm first, followed by Watson-Crick arm invasion, initiated at the tail. Based on this proposed hybridization mechanism, we designed next-generation bisLNAs with a novel linker able to stack to adjacent nucleobases, a new strategy previously not applied for any type of clamp-constructs. Although the Hoogsteen arm limits the invasion, upon incorporation of the stacking linker, bisLNA invasion is significantly more efficient than for non-clamp, or nucleotide-linker containing LNA-constructs. Further improvements were obtained by substituting LNA with 2'-glycylamino-LNA, contributing a positive charge. For regular bisLNAs a 14 nt tail significantly enhances invasion. However, when two stacking linkers were incorporated, tail-less bisLNAs were able to efficiently invade. Finally, successful targeting of plasmids inside bacteria clearly demonstrates that strand invasion can take place in a biologically relevant context. PMID- 26857550 TI - Antifungal therapies in murine infections by Candida kefyr. AB - Candida kefyr is an emerging pathogen able to cause disseminated infection, especially in immunocompromised patients. Although guidelines for the treatment of invasive candidiasis have been published, no specific recommendations against C. kefyr are available. We determine the in vitro killing activity of amphotericin B (AMB), fluconazole (FLC) and caspofungin (CFG) as well as their efficacy in a murine model of systemic infection by two C. kefyr strains. Time kill curves of AMB, FLC and CFG were determined in final volumes of 10 ml containing the assayed drugs ranged from 0.03 to 32 MUg ml-1 at different time points and efficacy of the drugs was evaluated in a systemic model of candidiasis, conducted in immunosuppressed mice, through survival, (1->3)-beta-D glucan levels in serum and fungal load in kidneys. AMB and CFG showed fungicidal and FLC fungistatic activity against both isolates. The three drugs were able to reduce fungal burden in kidneys and (1->3)-beta-D-glucan concentration in serum of infected mice, with CFG showing the highest efficacy, followed by FLC. In conclusion, CFG showed efficacy over AMB and FLC against the systemic candidiasis by C. kefyr. The established epidemiological cut-off for anidulafungin seems the best indicator of outcome for echinocandins. PMID- 26857551 TI - Nanoparticles based on quantum dots and a luminol derivative: implications for in vivo imaging of hydrogen peroxide by chemiluminescence resonance energy transfer. AB - Overproduction of hydrogen peroxide is involved in the pathogenesis of inflammatory diseases such as cancer and arthritis. To image hydrogen peroxide via chemiluminescence resonance energy transfer in the near-infrared wavelength range, we prepared quantum dots functionalized with a luminol derivative. PMID- 26857552 TI - Actigraphic sleep fragmentation, efficiency and duration associate with dietary intake in the Rotterdam Study. AB - Short self-reported sleep duration is associated with dietary intake and this association may partly mediate the link between short sleep and metabolic abnormalities. Subjective sleep measures, however, may be inaccurate and biased. The objective of this study was to evaluate the associations between actigraphic measures of sleep fragmentation, efficiency and duration and energy and macronutrient intakes. We used data from a subgroup of 439 participants of the population-based cohort, Rotterdam Study. Sleep was assessed using 7-day actigraphy and sleep diaries, and dietary data with a validated food frequency questionnaire. We assessed the associations of actigraphic sleep parameters with dietary intake using multivariable linear regression models. Higher sleep fragmentation was associated with 4.19 g lower carbohydrate intake per standard deviation of fragmentation {beta [95% confidence interval (CI) = -4.19 (-8.0, 0.3)]; P = 0.03}. Each additional percentage increase in sleep efficiency was associated with 11.1 kcal lower energy intake [beta (95% CI) = -11.1 (-20.6, 1.7); P = 0.02]. Furthermore, very short sleep duration (<5.5 h) was associated with 218.1 kcal higher energy intake [beta (95% CI = 218.06 (33.3, 402.8), P = 0.02], relative to the reference group (>=6.5 to <7.5 h). We observed associations between higher sleep fragmentation with lower carbohydrate intake, and both lower sleep efficiency and very short sleep duration (<5 h) with higher energy intake. The association between sleep and higher energy intake could mediate, in part, the link between short sleep or sleep fragmentation index and metabolic abnormalities. PMID- 26857553 TI - Blastocysts derivation from somatic cell fusion with premature oocytes (prematuration somatic cell fusion). AB - This study was undertaken to investigate the development of immature oocytes after their fusion with male somatic cells expressing red fluorescence protein (RFP). RFP-expressing cells were fused with immature oocytes, matured in vitro and then parthenogenetically activated. Somatic nuclei showed spindle formation, 1st polar body extrusion after in vitro maturation and protruded the 2nd polar body after parthenogenetic activation. RFP was expressed in the resultant embryos; two-cell stage and blastocysts. Chromosomal analysis showed aneuploidy in 81.82% of the resulting blastocysts while 18.18% of the resulting blastocysts were diploid. Among eight RFP-expressing blastocysts, Xist mRNAs was detected in six while Sry mRNA was detected in only one blastocyst. We propose "prematuration somatic cell fusion" as an approach to generate embryos using somatic cells instead of spermatozoa. The current approach, if improved, would assist production of embryos for couples where the male partner is sterile, however, genetic and chromosomal analysis of the resultant embryos are required before transfer to the mothers. PMID- 26857554 TI - Response to letter: limitations of human papillomavirus DNA testing in measuring previous exposure and vaccine protection. PMID- 26857555 TI - Breakdown pathways during oral processing of different breads: impact of crumb and crust structures. AB - Oral processing during bread consumption is a key process related to the dynamics of texture perceptions, sensory stimuli release and starch digestion. The aim of this study was to determine the respective contribution of bread properties (composition and structure of crumb and crust) and of the oral physiology of subjects to the breakdown pathways in the mouth. The properties of the in vivo bread bolus obtained from eight healthy subjects were studied at three key points in time during their oral processing. The progressive lubrication and breakdown of bread were observed, as well as the beginning of the enzymatic degradation of starch. The study showed that "time" was the factor responsible for the greatest variability in bolus properties. Breakdown pathways were established for crumbs with and without crust. The presence of crust modified the oral processing, increasing, for instance, the heterogeneity of particle size at the middle of the oral processing sequence. Moreover, the hydration capacity of crust contributed to high starch degradation at swallowing time, in comparison with crumb alone. The main subject characteristics impacting bolus properties were the in-mouth duration, the individual masticatory index and the mouth volume, while the main bread properties explaining the bolus properties were the initial composition and the water-absorbing capacity. We concluded that both crumb and crust structures had an impact on the oral processing, affecting the capacity of hydration, the rheology and the breakdown degree of the bolus. PMID- 26857556 TI - Envenomation by the invasive Pterois volitans species (lionfish) in the French West Indies--a two-year prospective study in Martinique. AB - CONTEXT: The invasion of the lionfish (Pterois volitans) in the French West Indies represents one of the most important marine invasions by alien species in history. Since its first recognition in Martinique in February 2011, the lionfish presence has strongly progressed, resulting in increasing envenomation cases. Our objective was to report features of lionfish envenomation and outcome. METHODS: A prospective study conducted at the Martinique University Hospital by the emergency departments, general practitioners, and the pre-hospital emergency ambulance service included all the patients referred from November 2011 to February 2014 for one or several stings by lionfish, as strongly suggested by the fish description and the association with marked local pain and edema. Recommended management included immersion of the affected body part in hot water at 35-40 degrees C for 60 min, analgesics, tetanus toxoid, and antibiotics. RESULTS: 117 patients [98M/19F; age: 42 +/- 14 years [mean +/- SD]; with significant past morbidities (16%)] were included. Envenomation resulted in marked pain and local edema (100%), paresthesia (90%), abdominal cramps (62%), extensive edema (53%), tachycardia (34%), skin rash (32%), gastrointestinal disorders (28%), fainting (27%), transient weakness (24%), hypertension (21%), hypotension (18%), hyperthermia (9%), bradycardia (3%), hypophosphatemia (12%), elevated aspartate aminotransferase (AST) (10%), and thrombocytopenia (3%). The sting was complicated by local infection (18%) including skin abscess (5%), cellulitis (3%), skin necrosis (3%), and septic arthritis (2%). 26 patients (22%) were hospitalized requiring surgery (8%). Lionfish stings were single (81%) or multiple (19%). Localization was preferentially at one upper (67%) or lower limb (32%). All patients actually improved. Based on multivariate analyses, pain duration > 24 h was significantly associated with skin eruption (p = 0.001) and muscle cramps (p = 0.0002). Local infectious complications occurred more frequently in patients presenting multiple stings (p = 0.008). Immersion in hot water (44%, performed less than 3 h after the sting in 36% of the cases) significantly reduced pain duration (p = 0.02) and local infection (p = 0.02). CONCLUSION: Lionfish represents a major health threat in Martinique with increasing envenomation and significant morbidities. Outcome is favorable if promptly managed, with possible reduction in pain duration and local infections with the rapid immersion of the stung body part in hot water. Our data encourage the authorities to develop investigations on the exact extent of the lionfish invasion and set up a regional taskforce to inform the ecosystem users and register all lionfish-attributed incidents. PMID- 26857557 TI - Microgreens: Production, shelf life, and bioactive components. AB - Microgreens are emerging specialty food products which are gaining popularity and increased attention nowadays. They are young and tender cotyledonary leafy greens that are found in a pleasing palette of colors, textures, and flavors. Microgreens are a new class of edible vegetables harvested when first leaves have fully expanded and before true leaves have emerged. They are gaining popularity as a new culinary ingredient. They are used to enhance salads or as edible garnishes to embellish a wide variety of other dishes. Common microgreens are grown mainly from mustard, cabbage, radish, buckwheat, lettuce, spinach, etc. The consumption of microgreens has nowadays increased due to higher concentrations of bioactive components such as vitamins, minerals, and antioxidants than mature greens, which are important for human health. However, they typically have a short shelf life due to rapid product deterioration. This review aimed to evaluate the postharvest quality, potential bioactive compounds, and shelf life of microgreens for proper management of this specialty produce. PMID- 26857558 TI - Efficacy and cost effectiveness of telemedicine for improving access to care in the Paris region: study protocols for eight trials. AB - BACKGROUND: With the development of information and communication technologies, telemedicine has been proposed as a way to improve patient management by facilitating access to appropriate diagnosis and treatment. The Paris Ile de France Regional Health Agency is currently funding a comprehensive program of telemedicine experiments. This article describes the protocols for the evaluation of the implementation of telemedicine in the Paris region. METHODS/DESIGN: Over 2,500 patients have been included in eight studies addressing the use of telemedicine in the context of specific diseases or settings. Two projects are randomized controlled trials, while the six other projects are based on before after designs (differences in differences studies). Based on the MAST model and the French national framework, we identified endpoints to assess the impact of telemedicine on five dimensions: clinical effectiveness, cost-effectiveness, security of the application, patient satisfaction and quality of life and perception of professionals. DISCUSSION: Telemedicine encompasses a wide range of services and stakeholders, and thus study protocols must be tailored to the specific constraints and interests of the users. TRIAL REGISTRATION: NCT02110433 (03/07/2014), NCT02157740 (05/27/2014), NCT02374697 (02/05/2015), NCT02157727 (05/27/2014), NCT02229279 (08/28/2014), NCT02368769 (02/05/2015), NCT02164747 (NCT02164747), NCT02309905 (11/27/2014). PMID- 26857560 TI - Clarification on the impact of cervarix vaccination on human papillomavirus infection and cervical cancer in the United Kingdom. PMID- 26857561 TI - Erratum to: Assessment of wild leafy vegetables traditionally consumed by the ethnic communities of Manipur, northeast India. PMID- 26857559 TI - A pharmacogenetic pilot study reveals MTHFR, DRD3, and MDR1 polymorphisms as biomarker candidates for slow atorvastatin metabolizers. AB - BACKGROUND: The genetic variation underlying atorvastatin (ATV) pharmacokinetics was evaluated in a Mexican population. Aims of this study were: 1) to reveal the frequency of 87 polymorphisms in 36 genes related to drug metabolism in healthy Mexican volunteers, 2) to evaluate the impact of these polymorphisms on ATV pharmacokinetics, 3) to classify the ATV metabolic phenotypes of healthy volunteers, and 4) to investigate a possible association between genotypes and metabolizer phenotypes. METHODS: A pharmacokinetic study of ATV (single 80-mg dose) was conducted in 60 healthy male volunteers. ATV plasma concentrations were measured by high-performance liquid chromatography mass spectrometry. Pharmacokinetic parameters were calculated by the non-compartmental method. The polymorphisms were determined with the PHARMAchip(r) microarray and the TaqMan(r) probes genotyping assay. RESULTS: Three metabolic phenotypes were found in our population: slow, normal, and rapid. Six gene polymorphisms were found to have a significant effect on ATV pharmacokinetics: MTHFR (rs1801133), DRD3 (rs6280), GSTM3 (rs1799735), TNFalpha (rs1800629), MDR1 (rs1045642), and SLCO1B1 (rs4149056). The combination of MTHFR, DRD3 and MDR1 polymorphisms associated with a slow ATV metabolizer phenotype. CONCLUSION: Further studies using a genetic preselection method and a larger population are needed to confirm these polymorphisms as predictive biomarkers for ATV slow metabolizers. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12614000851662, date registered: August 8, 2014. PMID- 26857563 TI - Effectiveness of an Electronic Booster Session Delivered to Mandated Students. AB - College student drinking continues to be a problem in the United States. Students who have violated campus alcohol policy are at particularly high risk for dangerous drinking. While Brief Alcohol Screening and Intervention for College Students (BASICS) has been found to be an effective strategy in reducing high risk drinking and associated consequences, questions remain about ways to further reduce risk or sustain changes associated with a face-to face intervention. The purpose of this study was to assess the effectiveness of a computer-delivered personalized feedback (electronic booster) delivered to policy violators who completed a mandated BASICS program. At 3-month post-intervention, 346 participants (60.4% male and 39.6% female) were randomized to one of two conditions: assessment only (n = 171) or electronic booster feedback (n = 175). Follow-up assessments were given to all participants at 3, 6, and 12-month post initial intervention. Both groups showed reductions in drinking after the in person BASICS intervention, but no additional reductions were seen with the addition of an electronic booster session. Findings suggest that although brief motivational interventions delivered in person to mandated students have been shown to be effective with mandated students, there is no additional benefit from an electronic booster session delivered 3-month post-intervention for this population. PMID- 26857562 TI - Porcine aminopeptidase N binds to F4+ enterotoxigenic Escherichia coli fimbriae. AB - F4(+) enterotoxigenic Escherichia coli (ETEC) strains cause diarrheal disease in neonatal and post-weaned piglets. Several different host receptors for F4 fimbriae have been described, with porcine aminopeptidase N (APN) reported most recently. The FaeG subunit is essential for the binding of the three F4 variants to host cells. Here we show in both yeast two-hybrid and pulldown assays that APN binds directly to FaeG, the major subunit of F4 fimbriae, from three serotypes of F4(+) ETEC. Modulating APN gene expression in IPEC-J2 cells affected ETEC adherence. Antibodies raised against APN or F4 fimbriae both reduced ETEC adherence. Thus, APN mediates the attachment of F4(+) E. coli to intestinal epithelial cells. PMID- 26857565 TI - Unilateral renal cystic disease in the left kidney. PMID- 26857564 TI - Characterizing exons and introns by regularity of nucleotide strings. AB - BACKGROUND: Translation of nucleotides into a numeric form has been approached in many ways and has allowed researchers to investigate the properties of protein coding sequences and noncoding sequences. Typically, more pronounced long-range correlations and increased regularity were found in intron-containing genes and in non-transcribed regulatory DNA sequences, compared to cDNA sequences or intron less genes. The regularity is assessed by spectral tools defined on numerical translates. In most popular approaches of numerical translation the resulting spectra depend on the assignment of numerical values to nucleotides. Our contribution is to propose and illustrate a spectra which remains invariant to the translation rules used in traditional approaches. RESULTS: We outline a methodology for representing sequences of DNA nucleotides as numeric matrices in order to analytically investigate important structural characteristics of DNA. This representation allows us to compute the 2-dimensional wavelet transformation and assess regularity characteristics of the sequence via the slope of the wavelet spectra. In addition to computing a global slope measure for a sequence, we can apply our methodology for overlapping sections of nucleotides to obtain an "evolutionary slope." To illustrate our methodology, we analyzed 376 gene sequences from the first chromosome of the honeybee. CONCLUSION: For the genes analyzed, we find that introns are significantly more regular (lead to more negative spectral slopes) than exons, which agrees with the results from the literature where regularity is measured on "DNA walks". However, unlike DNA walks where the nucleotides are assigned numerical values depending on nucleotide characteristics (purine-pyrimidine, weak-strong hydrogen bonds, keto-amino, etc.) or other spatial assignments, the proposed spectral tool is invariant to the assignment of nucleotides. Thus, ambiguity in numerical translation of nucleotides is eliminated. PMID- 26857566 TI - The regulation mechanism of apoptosis by visfatin in the mesenteric lymph nodes of LPS-treated rats. AB - Visfatin is an adipocytokine displaying multiple functional properties, which plays a role in the regulation of cell apoptosis and inflammation by an as yet unidentified mechanism. The aim of the present study was to determine if visfatin is involved in apoptosis pathway induced by LPS in rat Mesenteric lymph nodes (MLNs). Experimental rats were divided into four groups and MLNs samples were collected from each group. The morphological changes of the MLNs were examined by histological imaging. CD68 and ENPP1 were detected with immunohistochemistry and Western Blot. Apoptosis was evaluated with TUNEL and Flow Cytometry, the mRNA levels of the apoptosis-related genes were detected by qRT-PCR, and the protein levels of the apoptotic-related factors were detected by western blot. The main results showed that visfatin could significantly increase the macrophages in MLNs and prevent cell apoptosis from LPS-induced mesenteric lymph nodes, activate apoptotic signaling pathways and regulate the mRNA levels of the apoptosis related genes. Visfatin had a pro-apoptotic effect on normal MLNs, whereas it exerted an anti-apoptotic effect during LPS-induced cell apoptosis in rat MLNs. In short, visfatin plays a dual role in the apoptosis in rat MLNs, which is mediated by both the mitochondrial apoptotic pathway and the death-receptor apoptotic pathway. PMID- 26857567 TI - Excretion of radionuclides in human breast milk after nuclear medicine examinations. Biokinetic and dosimetric data and recommendations on breastfeeding interruption. PMID- 26857568 TI - Is dopamine transporter invariably impaired at the time of diagnosis in dementia with Lewy bodies? PMID- 26857569 TI - Differences in Host Cell Invasion and Salmonella Pathogenicity Island 1 Expression between Salmonella enterica Serovar Paratyphi A and Nontyphoidal S. Typhimurium. AB - Active invasion into nonphagocytic host cells is central to Salmonella enterica pathogenicity and dependent on multiple genes within Salmonella pathogenicity island 1 (SPI-1). Here, we explored the invasion phenotype and the expression of SPI-1 in the typhoidal serovarS Paratyphi A compared to that of the nontyphoidal serovarS Typhimurium. We demonstrate that while S. Typhimurium is equally invasive under both aerobic and microaerobic conditions, S. Paratyphi A invades only following growth under microaerobic conditions. Transcriptome sequencing (RNA-Seq), reverse transcription-PCR (RT-PCR), Western blot, and secretome analyses established that S. Paratyphi A expresses much lower levels of SPI-1 genes and secretes lesser amounts of SPI-1 effector proteins than S. Typhimurium, especially under aerobic growth. Bypassing the native SPI-1 regulation by inducible expression of the SPI-1 activator, HilA, considerably elevated SPI-1 gene expression, host cell invasion, disruption of epithelial integrity, and induction of proinflammatory cytokine secretion by S. Paratyphi A but not by S. Typhimurium, suggesting that SPI-1 expression is naturally downregulated inS Paratyphi A. Using streptomycin-treated mice, we were able to establish substantial intestinal colonization byS Paratyphi A and showed moderately higher pathology and intestinal inflammation in mice infected with S. Paratyphi A overexpressing hilA Collectively, our results reveal unexpected differences in SPI-1 expression between S. Paratyphi A andS Typhimurium, indicate that S. Paratyphi A host cell invasion is suppressed under aerobic conditions, and suggest that lower invasion in aerobic sites and suppressed expression of immunogenic SPI-1 components contributes to the restrained inflammatory infection elicited by S. Paratyphi A. PMID- 26857570 TI - Trypanosoma cruzi Causes Paralyzing Systemic Necrotizing Vasculitis Driven by Pathogen-Specific Type I Immunity in Mice. AB - Infectious agents are often considered potential triggers of chronic inflammatory disease, including autoimmunity; however, direct evidence is usually lacking. Here we show that following control of acute infection of mice with the myotropic Colombiana strain of Trypanosoma cruzi, parasites persisted in tissue at low levels associated with development of systemic necrotizing vasculitis. Lesions occurred in many but not all organs and tissues, with skeletal muscle arteries being the most severely affected, and were associated with myositis, atrophy, paresis/paralysis, and death. Histopathology showed fibrinoid vascular necrosis, rare amastigote nests within skeletal muscle myocytes, and massive leukocyte infiltrates composed mainly of inflammatory monocytes, F4/80(+)macrophages, and T. cruzi tetramer-specific CD8(+) T lymphocytes capable of producing gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) but not interleukin-17 (IL-17). T. cruzi-specific IgG was detected in sera from infected mice, but antibody deposits and neutrophilic inflammation were not features of the lesions. Thus,T. cruzi infection of mice may be a specific infectious trigger of paralyzing systemic necrotizing vasculitis most severely affecting skeletal muscle, driven by pathogen-specific type I immune responses. PMID- 26857571 TI - Local Generation of Kynurenines Mediates Inhibition of Neutrophil Chemotaxis by Uropathogenic Escherichia coli. AB - During epithelial infections, pathogenic bacteria employ an array of strategies to attenuate and evade host immune responses, including the influx of polymorphonuclear leukocytes (PMN; neutrophils). Among the most common bacterial infections in humans are those of the urinary tract, caused chiefly by uropathogenic Escherichia coli (UPEC). During the establishment of bacterial cystitis, UPEC suppresses innate responses via multiple independent strategies. We recently described UPEC attenuation of PMN trafficking to the urinary bladder through pathogen-specific local induction of indoleamine 2,3-dioxygenase (IDO), a tryptophan catabolic enzyme previously shown to have regulatory activity only in adaptive immunity. Here, we investigated the mechanism by which IDO induction attenuates PMN migration. Local tryptophan limitation, by which IDO is known to influence T cell longevity and proliferation, was not involved in its effect on PMN trafficking. Instead, metabolites in the IDO pathway, particularly L kynurenine, directly suppressed PMN transepithelial migration and induced an attached, spread morphology in PMN both at rest and in the presence of chemotactic stimuli. Finally, kynurenines represent known ligands of the mammalian aryl hydrocarbon receptor (AHR), and UPEC infection of Ahr(-/-)mice recapitulated the derepressed PMN recruitment observed previously in Ido1(-/ )mice. UPEC therefore suppresses neutrophil migration early in bacterial cystitis by eliciting an IDO-mediated increase in local production of kynurenines, which act through the AHR to impair neutrophil chemotaxis. PMID- 26857573 TI - Mice with Genetic Deletion of Group VIA Phospholipase A2beta Exhibit Impaired Macrophage Function and Increased Parasite Load in Trypanosoma cruzi-Induced Myocarditis. AB - Trypanosoma cruzi infection, which is the etiological agent of Chagas disease, is associated with intense inflammation during the acute and chronic phases. The pathological progression of Chagas disease is influenced by the infiltration and transmigration of inflammatory cells across the endothelium to infected tissues, which are carefully regulated processes involving several molecular mediators, including adhesion molecules and platelet-activating factor (PAF). We have shown that PAF production is dependent upon calcium-independent group VIA phospholipase A2beta (iPLA2beta) following infection of human coronary artery endothelial cells (HCAECs) with T. cruzi, suggesting that the absence of iPLA2beta may decrease the recruitment of inflammatory cells to the heart to manage parasite accumulation. Cardiac endothelial cells isolated from iPLA2beta-knockout (iPLA2beta-KO) mice infected withT. cruzi demonstrated decreased PAF production compared to that by cells isolated from wild-type (WT) mice but demonstrated increases in adhesion molecule expression similar to those seen in WT mice. Myocardial inflammation in iPLA2beta-KO mice infected with T. cruzi was similar in severity to that in WT mice, but the iPLA2beta-KO mouse myocardium contained more parasite pseudocysts. Upon activation, macrophages from iPLA2beta-KO mice produced significantly less nitric oxide (NO) and caused lessT. cruzi inhibition than macrophages from wild type mice. Thus, the absence of iPLA2beta activity does not influence myocardial inflammation, but iPLA2beta is essential forT. cruzi clearance. PMID- 26857572 TI - Novel Two-Step Hierarchical Screening of Mutant Pools Reveals Mutants under Selection in Chicks. AB - Contaminated chicken/egg products are major sources of human salmonellosis, yet the strategies used by Salmonella to colonize chickens are poorly understood. We applied a novel two-step hierarchical procedure to identify new genes important for colonization and persistence of Salmonella enterica serotype Typhimurium in chickens. A library of 182 S. Typhimurium mutants each containing a targeted deletion of a group of contiguous genes (for a total of 2,069 genes deleted) was used to identify regions under selection at 1, 3, and 9 days postinfection in chicks. Mutants in 11 regions were under selection at all assayed times (colonization mutants), and mutants in 15 regions were under selection only at day 9 (persistence mutants). We assembled a pool of 92 mutants, each deleted for a single gene, representing nearly all genes in nine regions under selection. Twelve single gene deletion mutants were under selection in this assay, and we confirmed 6 of 9 of these candidate mutants via competitive infections and complementation analysis in chicks. STM0580, STM1295, STM1297, STM3612, STM3615, and STM3734 are needed for Salmonella to colonize and persist in chicks and were not previously associated with this ability. One of these key genes, STM1297 (selD), is required for anaerobic growth and supports the ability to utilize formate under these conditions, suggesting that metabolism of formate is important during infection. We report a hierarchical screening strategy to interrogate large portions of the genome during infection of animals using pools of mutants of low complexity. Using this strategy, we identified six genes not previously known to be needed during infection in chicks, and one of these (STM1297) suggests an important role for formate metabolism during infection. PMID- 26857574 TI - Card9- and MyD88-Mediated Gamma Interferon and Nitric Oxide Production Is Essential for Resistance to Subcutaneous Coccidioides posadasii Infection. AB - Coccidioidomycosis is a potentially life-threatening respiratory disease which is endemic to the southwestern United States and arid regions of Central and South America. It is responsible for approximately 150,000 infections annually in the United States alone. Almost every human organ has been reported to harbor parasitic cells of Coccidioides spp. in collective cases of the disseminated form of this mycosis. Current understanding of the mechanisms of protective immunity against lung infection has been largely derived from murine models of pulmonary coccidioidomycosis. However, little is known about the nature of the host response to Coccidioides in extrapulmonary tissue. Primary subcutaneous coccidioidal infection is rare but has been reported to result in disseminated disease. Here, we show that activation of MyD88 and Card9 signal pathways are required for resistance to Coccidioides infection following subcutaneous challenge of C57BL/6 mice, which correlates with earlier findings of the protective response to pulmonary infection. MyD88(-/-) andCard9(-/-) mice recruited reduced numbers of T cells, B cells, and neutrophils to the Coccidioides-infected hypodermis com pared to wild-type mice; however, neutrophils were dispensable for resistance to skin infection. Further studies have shown that gamma interferon (IFN-gamma) production and activation of Th1 cells characterize resistance to subcutaneous infection. Furthermore, activation of a phagosomal enzyme, inducible nitric oxide synthase, which is necessary for NO production, is a requisite for fungal clearance in the hypodermis. Collectively, our data demonstrate that MyD88- and Card9-mediated IFN-gamma and nitric oxide production is essential for protection against subcutaneous Coccidioides infection. PMID- 26857576 TI - Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis. AB - Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics,S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival. PMID- 26857575 TI - XerC Contributes to Diverse Forms of Staphylococcus aureus Infection via agr Dependent and agr-Independent Pathways. AB - We demonstrate that mutation of xerC, which reportedly encodes a homologue of an Escherichia coli recombinase, limits biofilm formation in the methicillin resistant Staphylococcus aureus strain LAC and the methicillin-sensitive strain UAMS-1. This was not due to the decreased production of the polysaccharide intracellular adhesin (PIA) in either strain because the amount of PIA was increased in a UAMS-1xerC mutant and undetectable in both LAC and its isogenic xerC mutant. Mutation of xerC also resulted in the increased production of extracellular proteases and nucleases in both LAC and UAMS-1, and limiting the production of either class of enzymes increased biofilm formation in the isogenic xerC mutants. More importantly, the limited capacity to form a biofilm was correlated with increased antibiotic susceptibility in both strains in the context of an established biofilm in vivo. Mutation of xerC also attenuated virulence in a murine bacteremia model, as assessed on the basis of the bacterial loads in internal organs and overall lethality. It also resulted in the decreased accumulation of alpha toxin and the increased accumulation of protein A. These findings suggest that xerC may impact the functional status of agr. This was confirmed by demonstrating the reduced accumulation of RNAIII and AgrA in LAC and UAMS-1xerC mutants. However, this cannot account for the biofilm-deficient phenotype of xerC mutants because mutation of agr did not limit biofilm formation in either strain. These results demonstrate that xerC contributes to biofilm associated infections and acute bacteremia and that this is likely due to agr independent and -dependent pathways, respectively. PMID- 26857577 TI - Limitations of Murine Models for Assessment of Antibody-Mediated Therapies or Vaccine Candidates against Staphylococcus epidermidis Bloodstream Infection. AB - Staphylococcus epidermidis is normally a commensal colonizer of human skin and mucus membranes, but, due to its ability to form biofilms on indwelling medical devices, it has emerged as a leading cause of nosocomial infections. Bacteremia or bloodstream infection is a frequent and costly complication resulting from biofilm fouling of medical devices. Our goal was to develop a murine model of S. epidermidis infection to identify potential vaccine targets for the prevention of S. epidermidis bacteremia. However, assessing the contribution of adaptive immunity to protection against S. epidermidis challenge was complicated by a highly efficacious innate immune response in mice. Naive mice rapidly cleared S. epidermidis infections from blood and solid organs, even when the animals were immunocompromised. Cyclophosphamide-mediated leukopenia reduced the size of the bacterial challenge dose required to cause lethality but did not impair clearance after a nonlethal challenge. Nonspecific innate immune stimulation, such as treatment with a Toll-like receptor 4 (TLR4) agonist, enhanced bacterial clearance. TLR2 signaling was confirmed to accelerate the clearance of S. epidermidis bacteremia, but TLR2(-/-)mice could still resolve a bloodstream infection. Furthermore, TLR2 signaling played no role in the clearance of bacteria from the spleen. In conclusion, these data suggest that S. epidermidis bloodstream infection is cleared in a highly efficient manner that is mediated by both TLR2-dependent and -independent innate immune mechanisms. The inability to establish a persistent infection in mice, even in immunocompromised animals, rendered these murine models unsuitable for meaningful assessment of antibody mediated therapies or vaccine candidates. PMID- 26857579 TI - Galectin-3 Plays an Important Role in Innate Immunity to Gastric Infection by Helicobacter pylori. AB - We studied the role of galectin-3 (Gal3) in gastric infection by Helicobacter pylori We first demonstrated that Gal3 was selectively expressed by gastric surface epithelial cells and abundantly secreted into the surface mucus layer. We next inoculated H. pylori Sydney strain 1 into wild-type (WT) and Gal3-deficient mice using a stomach tube. At 2 weeks postinoculation, the bacterial cells were mostly trapped within the surface mucus layer in WT mice. In sharp contrast, they infiltrated deep into the gastric glands in Gal3-deficient mice. Bacterial loads in the gastric tissues were also much higher in Gal3-deficient mice than in WT mice. At 6 months postinoculation,H. pylori had successfully colonized within the gastric glands of both WT and Gal3-deficient mice, although the bacterial loads were still higher in the latter. Furthermore, large lymphoid clusters mostly consisting of B cells were frequently observed in the gastric submucosa of Gal3 deficient mice.In vitro, peritoneal macrophages from Gal3-deficient mice were inefficient in killing engulfed H. pylori Furthermore, recombinant Gal3 not only induced rapid aggregation of H. pylori but also exerted a potent bactericidal effect on H. pylori as revealed by propidium iodide uptake and a morphological shift from spiral to coccoid form. However, a minor fraction of bacterial cells, probably transient phase variants of Gal3-binding sugar moieties, escaped killing by Gal3. Collectively, our data demonstrate that Gal3 plays an important role in innate immunity to infection and colonization of H. pylori. PMID- 26857578 TI - Porphyromonas gingivalis Outer Membrane Vesicles Induce Selective Tumor Necrosis Factor Tolerance in a Toll-Like Receptor 4- and mTOR-Dependent Manner. AB - Porphyromonas gingivalis is an important member of the anaerobic oral flora. Its presence fosters growth of periodontal biofilm and development of periodontitis. In this study, we demonstrated that lipophilic outer membrane vesicles (OMV) shed from P. gingivalis promote monocyte unresponsiveness to live P. gingivalis but retain reactivity to stimulation with bacterial DNA isolated from P. gingivalis or AIM2 ligand poly(dA.dT). OMV-mediated tolerance of P. gingivalis is characterized by selective abrogation of tumor necrosis factor (TNF). Neutralization of interleukin-10 (IL-10) during OMV challenge partially restores monocyte responsiveness toP. gingivalis; full reactivity toP. gingivalis can be restored by inhibition of mTOR signaling, which we previously identified as the major signaling pathway promoting Toll-like receptor 2 and Toll-like receptor 4 (TLR2/4)-mediated tolerance in monocytes. However, despite previous reports emphasizing a central role of TLR2 in innate immune recognition of P. gingivalis, our current findings highlight a selective role of TLR4 in the promotion of OMV mediated TNF tolerance: only blockade of TLR4-and not of TLR2-restores responsiveness toP. gingivalis Of further note, OMV-mediated tolerance is preserved in the presence of cytochalasin B and chloroquine, indicating that triggering of surface TLR4 is sufficient for this effect. Taking the results together, we propose that P. gingivalis OMV contribute to local immune evasion of P. gingivalis by hampering the host response. PMID- 26857581 TI - The Biosynthesis of Infrared-Emitting Quantum Dots in Allium Fistulosum. AB - The development of simple routes to emissive solid-state materials is of paramount interest, and in this report we describe the biosynthesis of infrared emitting quantum dots in a living plant via a mutual antagonistic reaction. Exposure of common Allium fistulosum to mercury and tellurium salts under ambient conditions resulted in the expulsion of crystalline, non-passivated HgTe quantum dots that exhibited emissive characteristics in the near-infrared spectral region, a wavelength range that is important in telecommunications and solar energy conversion. PMID- 26857580 TI - Predictive value of drain amylase content for peripancreatic inflammatory fluid collections after laparoscopic (assisted) distal gastrectomy. AB - BACKGROUND: Laparoscopic (assisted) distal gastrectomy (LDG) with radical lymphadenectomy for gastric cancer has been widely conducted, particularly in the Far East. Peripancreatic inflammatory fluid collection (PIFC) is a serious and frequent postoperative complication after LDG for gastric cancer. The aim of this study was to evaluate the diagnostic performance of drain amylase content (D-AMY) for clinically relevant PIFC after LDG. METHODS: Two hundred and sixty-four patients who underwent LDG with prophylactic drains were enrolled. The predictive value of D-AMY on postoperative day (POD) 1 and POD 3 in the diagnosis of PIFC was evaluated. RESULTS: Twenty (7.6 %) patients experienced postoperative PIFC. Area under the curve in terms of receiver operating characteristics curve analysis of D-AMY on POD 1 was 0.801, and the optimal cutoff value for prediction of PIFC was 904 IU/l, with 98.2 % negative predictive value. Another cutoff was proposed as 4078 IU/l, with 92.2 % specificity. Multivariable analyses identified D-AMY on POD 1 >=900 and >=4000 IU/l as independent diagnostic factors for PIFC. Among patients at high risk of PIFC (D-AMY on POD 1 >=900 IU/l), those who on POD 3 retained D-AMY value in excess of 31.2 % of the D-AMY value on POD 1 were more likely to experience PIFC compared with those with a pronounced decrease in D AMY. CONCLUSIONS: D-AMY on POD 1 serves as a predictive factor for clinically relevant PIFC after LDG. Time-dependent changes in D-AMY can also be used for determining management of drains in patients at high risk of PIFC. PMID- 26857582 TI - Extensive and ulcerated malignant proliferating trichilemmal (pilar) tumour, arising from multiple, large, degenerated trichilemmal (pilar) cysts. AB - We report a rare case of a 61-year-old homeless man with a 15-year history of multiple trichilemmal cysts that served as a forerunner for the emergence of a malignant proliferating pilar tumour. The patient presented multiple, large, purulent, ulcerated lesions ranging from 10 to 150 mm in diameter, covering most of the scalp, with large areas superimposed by extensive myiasis infestation. The patient presented with no other major clinical findings. A CT scan showed no detectable signs of local or distant metastatic invasion. Initial supportive treatment was implemented. Given the extent of the injury, further surgical excision was considered, which required transfer to a specialised surgical centre. This social case is of educational value, as it can raise clinician awareness about the ability of trichilemmal cysts to undergo malignant transformation. Additionally, it highlights the importance of adequate social assistance structures for patients in need. PMID- 26857583 TI - Ileal pouch functional outlet obstruction. AB - Small bowel obstructions (SBOs) are common in patients who have undergone Ileal J pouch-anal anastomosis (IPAA) surgery. SBO may be caused by stenosis of the diverting ileostomy, volvulus, internal hernia, adhesive bands, anastomotic stricture or intra-abdominal adhesions. Functional outlet obstruction is an important alternative diagnosis to consider in a patient post-IPAA presenting with obstructive symptoms. Recognition of this condition can prevent unnecessary surgery and save the patient from presenting repeatedly with obstructive symptoms. PMID- 26857584 TI - Reversed halo sign in cryptogenic organising pneumonia. PMID- 26857585 TI - Phaeochromocytoma presenting with ST segment elevation myocardial infarction. AB - Phaeochromocytoma is a rare endocrine disorder with different cardiovascular presentations. In this brief report, we discuss a case of a 59-year-old woman who presented with acute ST segment elevation myocardial infarction secondary to phaeochromocytoma. Coronary angiogram showed non-obstructive coronary artery disease. PMID- 26857586 TI - Dunbar syndrome following liver transplantation. PMID- 26857587 TI - Longitudinal assessment of maternal-fetal Doppler parameters and maternal plasma level of matrix metalloproteinases 2 and 9. AB - OBJECTIVE: To assess the behavior as well as the comparison between maternal circulating level of biochemical markers (matrix metalloproteinases - MMP-9 and MMP-2) and maternal-fetal Doppler parameters in all three trimesters of pregnancy. METHODS: We performed a prospective longitudinal study with 33 healthy pregnant women in three periods of pregnancy: A1 (12w0-14w6d), A2 (22w0d-24w6d) and A3 (34w0d and 36w6d). The following maternal Doppler parameters were assessed: mean pulsatility index (PI) uterine artery, resistance index (RI) umbilical artery and RI middle cerebral artery. The maternal plasma concentrations of MMP-2 and MMP-9 were determined by enzyme immunoassay (ELISA). To compare two (A2 and A3) and three assessments (A1, A2 and A3), we used the paired Student t test and linear regression, respectively. To compare the biomechanical markers and maternal-fetal Doppler parameter, we used the Spearman correlation coefficient (rho). RESULTS: We observed a significant decrease of PI uterine artery Doppler over the three trimesters of pregnancy (p < 0.01) and RI umbilical artery Doppler overt second to three trimester of pregnancy (p < 0.05). We did not observe significant difference in the maternal plasma level of MMP-2 and MMP-9 between the three trimesters. We did not also observe significant correlation between biochemical markers and maternal-fetal Doppler parameters. CONCLUSION: Maternal circulating level of MMPs did not modify throughout pregnancy and it did not show correlation with maternal-fetal Doppler parameters. PMID- 26857588 TI - Detection of creatinine in exhaled breath of humans with chronic kidney disease by extractive electrospray ionization mass spectrometry. AB - Exhaled breath contains chemicals that have a diagnostic value in human pathologies. Here in vivo breath analysis of creatinine has been demonstrated by constructing a novel platform based on extractive electrospray ionization mass spectrometry (EESI-MS) without sample pretreatment. Under optimized experimental conditions, the limit of creatinine detection in breath was 30.57 ng L(-1), and the linear range of detection was from 0.3 MUg L(-1) to 100 MUg L(-1). The concentration range of creatinine in the exhaled breath of 50 volunteers with chronic kidney disease was from 42 pptv to 924 pptv, and the range of the relative standard deviations was from 9.3% to 19.2%. The method provides high sensitivity, high specificity and high speed for semi-quantitative analysis of creatinine in exhaled human breath. PMID- 26857589 TI - The Progression of Cholelithiasis to Gallstone Ileus: Do Large Gallstones Warrant Surgery? AB - Gallstone ileus is a rare cause of small bowel obstruction, classically occurring in patients with recurrent cholecystitis. The incidence of biliary enteric fistula and gallstone ileus in patients with large, asymptomatic gallstones is not known. We report a case of gallstone ileus, which occurred in the setting of a large, asymptomatic gallstone. This case suggests that large gallstones may warrant cholecystectomy, even in asymptomatic patients. PMID- 26857590 TI - Extragastrointestinal Stromal Tumor Presenting as Omental Cyst. AB - INTRODUCTION: Extragastrointestinal stromal tumors (EGIST) are rarer counterparts of gastrointestinal stromal tumors (GIST) in omentum, mesentery, and retroperitoneum. CASE REPORT: Hereby, authors present a 47-year-old man with abdominal mass whose abdominal CT scan revealed a large septated cystic mass measuring 16 cm in largest diameter. The mass was aspirated and resected by laparotomy. Pathologic examination exhibited a mesenchymal spindle cell neoplasm which was immunohistochemically reactive for CD117 and SMA. Thus, the diagnosis of extragastrointestinal stromal tumor was made. DISCUSSION: A cystic EGIST in omentum falls in the differential diagnoses of omental cystic lesions which include omental cyst, mesenteric teratoma, cystic mesothelioma, cystic spindle cell tumors, pseudomyxoma peritonei, pancreatic pseudocyst, and complicated ascites. Therefore, proper diagnosis of cystic GIST is of great importance in respect to different behavior, management, and complications in comparison to its mimickers and GI counterparts. PMID- 26857591 TI - Long-Term Survival After Complications Following Major Abdominal Surgery. AB - INTRODUCTION: Postoperative complications have been associated with decreased long-term survival in cardiac, orthopedic, and vascular surgery. For major abdominal surgery research, conflicting evidence is reported in smaller studies. The aim of this study was to assess the effect of complications on long-term survival in major abdominal surgery. MATERIAL AND METHODS: An observational cohort study was conducted of 861 consecutive patients that underwent major abdominal surgery between January 2009 and March 2014, with prospective assessment of the survival status. The effect of postoperative complications on survival was assessed. RESULTS: Postoperative complications were associated with decreased survival, even after applying correction for 30-day mortality (p < 0.001). Stratified Cox regression analysis depicted postoperative complications to be an important predictor for survival in upper gastrointestinal and female hepatopancreaticobiliary patients. Correction was applied for age, gender, BMI, ASA classification, radicality, and positive lymph node status. CONCLUSION: These results further indicate the importance of prevention and early diagnosis and treatment of complications. Etiological factors are believed to be both sustained levels of inflammatory markers, as well as attenuated immune response in malignancy with subsequent cancer cell seeding. Future research should aim to prevent and early diagnose postoperative complications to prevent morbidity and mortality not only in the early postoperative phase, but also in the long term. PMID- 26857592 TI - Pentiptycene-Based Luminescent Cu (II) MOF Exhibiting Selective Gas Adsorption and Unprecedentedly High-Sensitivity Detection of Nitroaromatic Compounds (NACs). AB - The assembly of a fluorescent pentiptycene-based ligand with copper ion resulted in the formation of a 3D porous metal-organic framework (UPC-21) based on well known paddlewheel SBUs. UPC-21 exhibits selective adsorption of CO2 over CH4 and N2 at 273 K and 295 K, C2H2 over CH4 at 273 K. The most significant performance of UPC-21 is its highly efficient detection of NACs such as 4-NP, 1,4-DNB, NB, and 1,3-DNB with the calculated quenching constants, Ksv, being 3.097 * 10(6), 1.406 * 10(6), 4.420 * 10(5), and 1.498 * 10(5 )M(-1) for 4-NP, 1,4-DNB, NB, 1,3 DNB, respectively, which keeps a record on the fluorescence detection of NACs. This is the first porous Cu(II) MOF that exhibits fluorescent detection of NACs with high sensitivities. PMID- 26857593 TI - Wheezing Patterns in Early Childhood and the Risk of Respiratory and Allergic Disease in Adolescence. PMID- 26857594 TI - Light-inducible genetic engineering and control of non-homologous end-joining in industrial eukaryotic microorganisms: LML 3.0 and OFN 1.0. AB - Filamentous fungi play important roles in the production of plant cell-wall degrading enzymes. In recent years, homologous recombinant technologies have contributed significantly to improved enzymes production and system design of genetically manipulated strains. When introducing multiple gene deletions, we need a robust and convenient way to control selectable marker genes, especially when only a limited number of markers are available in filamentous fungi. Integration after transformation is predominantly nonhomologous in most fungi other than yeast. Fungal strains deficient in the non-homologous end-joining (NHEJ) pathway have limitations associated with gene function analyses despite they are excellent recipient strains for gene targets. We describe strategies and methods to address these challenges above and leverage the power of resilient NHEJ deficiency strains. We have established a foolproof light-inducible platform for one-step unmarked genetic modification in industrial eukaryotic microorganisms designated as 'LML 3.0', and an on-off control protocol of NHEJ pathway called 'OFN 1.0', using a synthetic light-switchable transactivation to control Cre recombinase-based excision and inversion. The methods provide a one step strategy to sequentially modify genes without introducing selectable markers and NHEJ-deficiency. The strategies can be used to manipulate many biological processes in a wide range of eukaryotic cells. PMID- 26857595 TI - Metabolically Healthy Obesity and Development of Chronic Kidney Disease: A Cohort Study. AB - BACKGROUND: The risk for chronic kidney disease (CKD) among obese persons without obesity-related metabolic abnormalities, called metabolically healthy obesity, is largely unexplored. OBJECTIVE: To investigate the risk for incident CKD across categories of body mass index in a large cohort of metabolically healthy men and women. DESIGN: Prospective cohort study. SETTING: Kangbuk Samsung Health Study, Kangbuk Samsung Hospital, Seoul, South Korea. PARTICIPANTS: 62 249 metabolically healthy, young and middle-aged men and women without CKD or proteinuria at baseline. MEASUREMENTS: Metabolic health was defined as a homeostasis model assessment of insulin resistance less than 2.5 and absence of any component of the metabolic syndrome. Underweight, normal weight, overweight, and obesity were defined as a body mass index less than 18.5 kg/m2, 18.5 to 22.9 kg/m2, 23 to 24.9 kg/m2, and 25 kg/m2 or greater, respectively. The outcome was incident CKD, defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2. RESULTS: During 369 088 person-years of follow-up, 906 incident CKD cases were identified. The multivariable-adjusted differences in 5-year cumulative incidence of CKD in underweight, overweight, and obese participants compared with normal weight participants were -4.0 (95% CI, -7.8 to -0.3), 3.5 (CI, 0.9 to 6.1), and 6.7 (CI, 3.0 to 10.4) cases per 1000 persons, respectively. These associations were consistently seen in all clinically relevant subgroups. LIMITATION: Chronic kidney disease was identified by a single measurement at each visit. CONCLUSION: Overweight and obesity are associated with an increased incidence of CKD in metabolically healthy young and middle-aged participants. These findings show that metabolically healthy obesity is not a harmless condition and that the obese phenotype, regardless of metabolic abnormalities, can adversely affect renal function. PRIMARY FUNDING SOURCE: None. PMID- 26857602 TI - Error in Author's Name. PMID- 26857603 TI - In Memoriam: Oliver Sacks, MD (July 9, 1933, to August 30, 2015). PMID- 26857599 TI - Meta-analysis of genome-wide association studies of anxiety disorders. PMID- 26857596 TI - Subcortical volumetric abnormalities in bipolar disorder. AB - Considerable uncertainty exists about the defining brain changes associated with bipolar disorder (BD). Understanding and quantifying the sources of uncertainty can help generate novel clinical hypotheses about etiology and assist in the development of biomarkers for indexing disease progression and prognosis. Here we were interested in quantifying case-control differences in intracranial volume (ICV) and each of eight subcortical brain measures: nucleus accumbens, amygdala, caudate, hippocampus, globus pallidus, putamen, thalamus, lateral ventricles. In a large study of 1710 BD patients and 2594 healthy controls, we found consistent volumetric reductions in BD patients for mean hippocampus (Cohen's d=-0.232; P=3.50 * 10-7) and thalamus (d=-0.148; P=4.27 * 10-3) and enlarged lateral ventricles (d=-0.260; P=3.93 * 10-5) in patients. No significant effect of age at illness onset was detected. Stratifying patients based on clinical subtype (BD type I or type II) revealed that BDI patients had significantly larger lateral ventricles and smaller hippocampus and amygdala than controls. However, when comparing BDI and BDII patients directly, we did not detect any significant differences in brain volume. This likely represents similar etiology between BD subtype classifications. Exploratory analyses revealed significantly larger thalamic volumes in patients taking lithium compared with patients not taking lithium. We detected no significant differences between BDII patients and controls in the largest such comparison to date. Findings in this study should be interpreted with caution and with careful consideration of the limitations inherent to meta-analyzed neuroimaging comparisons. PMID- 26857598 TI - KCNH2-3.1 expression impairs cognition and alters neuronal function in a model of molecular pathology associated with schizophrenia. AB - Overexpression in humans of KCNH2-3.1, which encodes a primate-specific and brain selective isoform of the human ether-a-go-go-related potassium channel, is associated with impaired cognition, inefficient neural processing and schizophrenia. Here, we describe a new mouse model that incorporates the KCNH2 3.1 molecular phenotype. KCNH2-3.1 transgenic mice are viable and display normal sensorimotor behaviors. However, they show alterations in neuronal structure and microcircuit function in the hippocampus and prefrontal cortex, areas affected in schizophrenia. Specifically, in slice preparations from the CA1 region of the hippocampus, KCNH2-3.1 transgenic mice have fewer mature dendrites and impaired theta burst stimulation long-term potentiation. Abnormal neuronal firing patterns characteristic of the fast deactivation kinetics of the KCNH2-3.1 isoform were also observed in prefrontal cortex. Transgenic mice showed significant deficits in a hippocampal-dependent object location task and a prefrontal cortex-dependent T-maze working memory task. Interestingly, the hippocampal-dependent alterations were not present in juvenile transgenic mice, suggesting a developmental trajectory to the phenotype. Suppressing KCNH2-3.1 expression in adult mice rescues both the behavioral and physiological phenotypes. These data provide insight into the mechanism of association of KCNH2-3.1 with variation in human cognition and neuronal physiology and may explain its role in schizophrenia. PMID- 26857597 TI - Assessing the genetic overlap between BMI and cognitive function. AB - Obesity and low cognitive function are associated with multiple adverse health outcomes across the life course. They have a small phenotypic correlation (r= 0.11; high body mass index (BMI)-low cognitive function), but whether they have a shared genetic aetiology is unknown. We investigated the phenotypic and genetic correlations between the traits using data from 6815 unrelated, genotyped members of Generation Scotland, an ethnically homogeneous cohort from five sites across Scotland. Genetic correlations were estimated using the following: same-sample bivariate genome-wide complex trait analysis (GCTA)-GREML; independent samples bivariate GCTA-GREML using Generation Scotland for cognitive data and four other samples (n=20 806) for BMI; and bivariate LDSC analysis using the largest genome wide association study (GWAS) summary data on cognitive function (n=48 462) and BMI (n=339 224) to date. The GWAS summary data were also used to create polygenic scores for the two traits, with within- and cross-trait prediction taking place in the independent Generation Scotland cohort. A large genetic correlation of 0.51 (s.e. 0.15) was observed using the same-sample GCTA-GREML approach compared with -0.10 (s.e. 0.08) from the independent-samples GCTA-GREML approach and -0.22 (s.e. 0.03) from the bivariate LDSC analysis. A genetic profile score using cognition-specific genetic variants accounts for 0.08% (P=0.020) of the variance in BMI and a genetic profile score using BMI-specific variants accounts for 0.42% (P=1.9 * 10(-7)) of the variance in cognitive function. Seven common genetic variants are significantly associated with both traits at P<5 * 10(-5), which is significantly more than expected by chance (P=0.007). All these results suggest there are shared genetic contributions to BMI and cognitive function. PMID- 26857605 TI - Bio-Source of di-n-butyl phthalate production by filamentous fungi. AB - Although DBP (di-n-butyl phthalate) is commonly encountered as an artificially synthesized plasticizer with potential to impair fertility, we confirm that it can also be biosynthesized as microbial secondary metabolites from naturally occurring filamentous fungi strains cultured either in an artificial medium or natural water. Using the excreted crude enzyme from the fungi for catalyzing a variety of substrates, we found that the fungal generation of DBP was largely through shikimic acid pathway, which was assembled by phthalic acid with butyl alcohol through esterification. The DBP production ability of the fungi was primarily influenced by fungal spore density and incubation temperature. This study indicates an important alternative natural waterborne source of DBP in addition to artificial synthesis, which implied fungal contribution must be highlighted for future source control and risk management of DBP. PMID- 26857606 TI - Chemical insights into the roles of nanowire cores on the growth and supercapacitor performances of Ni-Co-O/Ni(OH)2 core/shell electrodes. AB - Nanostructured core/shell electrodes have been experimentally demonstrated promising for high-performance electrochemical energy storage devices. However, chemical insights into the significant roles of nanowire cores on the growth of shells and their supercapacitor behaviors still remain as a research shortfall. In this work, by substituting 1/3 cobalt in the Co3O4 nanowire core with nickel, a 61% enhancement of the specific mass-loading of the Ni(OH)2 shell, a tremendous 93% increase of the volumetric capacitance and a superior cyclability were achieved in a novel NiCo2O4/Ni(OH)2 core/shell electrode in contrast to a Co3O4/Ni(OH)2 one. A comparative study suggested that not only the growth of Ni(OH)2 shells but also the contribution of cores were attributed to the overall performances. Importantly, their chemical origins were revealed through a theoretical simulation of the core/shell interfacial energy changes. Besides, asymmetric supercapacitor devices and applications were also explored. The scientific clues and practical potentials obtained in this work are helpful for the design and analysis of alternative core/shell electrode materials. PMID- 26857607 TI - Algicidal effect of hybrid peptides as potential inhibitors of harmful algal blooms. AB - OBJECTIVES: To biochemically characterize synthetic peptides to control harmful algal blooms (HABs) that cause red tides in marine water ecosystems. RESULTS: We present an analysis of several short synthetic peptides and their efficacy as algicidal agents. By altering the amino acid composition of the peptides we addressed the mode of algicidal action and determine the optimal balance of cationic and hydrophobic content for killing. In a controlled setting, these synthetic peptides disrupted both plasma and chloroplast membranes of several species known to result in HABs. This disruption was a direct result of the hydrophobic and cationic content of the peptide. Furthermore, by using an anti HAB bioassay in scallops, we determined that these peptides were algicidal without being cytotoxic to other marine organisms. CONCLUSIONS: These synthetic peptides may prove promising for general marine ecosystem remediation where HABs have become widespread and resulted in serious economic loss. PMID- 26857608 TI - Functional expression of human serum albumin-tandem thrombopoietin mimetic peptide fusion protein as a novel thrombopoietin analog in Pichia pastoris. AB - OBJECTIVES: To develop a novel thrombopoietin (TPO) analog by fusing the tandem TPO mimetic peptide (TMP-TMP) to human serum albumin (HSA) and performing functional expression of recombinant fusion protein HSA-TMP-TMP. RESULTS: After optimizing the fusion orientation in shake-flask culture, HSA-TMP-TMP was expressed at 0.4 g/l in Pichia pastoris grown in a 20 l bioreactor, during which pH was controlled at 5 by addition of NH4OH and citric acid. The fusion protein significantly activated signal transducer and activator of transcription-mediated transcription in TPO receptor-dependent manner, which was demonstrated by a luciferase reporter assay. Following subcutaneous administration, HSA-TMP-TMP effectively stimulated the platelet production in healthy mice in a dose dependent manner. CONCLUSION: Successful expression of HSA-TMP-TMP fusion protein in P. pastoris was achieved and the recombinant HSA-TMP-TMP is a promising TPO analog. PMID- 26857609 TI - Comparison of adult stem cells derived from multiple stem cell niches. AB - OBJECTIVES: Adult stem cells (ASCs) have great potential for tissue regeneration; however, comparative studies of ASCs from different niches are required to understand the characteristics of each population for their potential therapeutic uses. RESULTS: We compared the proliferation, stem cell marker expression, and differentiation potential of ASCs from bone marrow, skin dermis, and adipose tissue. ASCs from bone marrow and skin dermis showed 50-100 % increased proliferation in comparison to the ASCs from adipose tissues. Furthermore, ASCs from each stem cell niche showed differential expression of stem cell marker genes, and preferentially differentiated into cell types of their tissue of origin. CONCLUSION: Different characters of each ASC might be major factors for their effective use for therapeutics and tissue regeneration. PMID- 26857610 TI - Highly enantioselective production of a chiral intermediate of sitagliptin by a novel isolate of Pseudomonas pseudoalcaligenes. AB - OBJECTIVE: To produce (S)-3-hydroxy-1-(3-(trifluoromethyl)-5,6 dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-4-(2,4,5-trifluorophenyl)butan-1 one (S)-1 from 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1,2,4]triazolo[4,3 a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl)butan-2-one (2) by microbial bioreduction. RESULTS: A new isolate of Pseudomonas pseudoalcaligenes reduced enantioselectively prochiral ketone 2 to chiral alcohol (S)-1. Whole cells of the bacterium were tolerant towards 20 % (v/v) DMSO and 10 g 2/l. Under the optimal conditions, the preparative-scale bioreduction yielded (S)-1 at 90 % yield and >99 % ee. Cells could be re-used with the yield and ee of product being 45 % and >99 %, respectively, after five cycles. CONCLUSION: Bioreduction using whole cells of P. pseudoalcaligenes is an attractive approach to produce (S)-1, as a chiral intermediate of the anti-diabetic drug, sitagliptin. PMID- 26857612 TI - CRISPR/Cas9-mediated gene knockout in the mouse brain using in utero electroporation. AB - The CRISPR/Cas9 system has recently been adapted for generating knockout mice to investigate physiological functions and pathological mechanisms. Here, we report a highly efficient procedure for brain-specific disruption of genes of interest in vivo. We constructed pX330 plasmids expressing humanized Cas9 and single-guide RNAs (sgRNAs) against the Satb2 gene, which encodes an AT-rich DNA-binding transcription factor and is responsible for callosal axon projections in the developing mouse brain. We first confirmed that these constructs efficiently induced double-strand breaks (DSBs) in target sites of exogenous plasmids both in vitro and in vivo. We then found that the introduction of pX330-Satb2 into the developing mouse brain using in utero electroporation led to a dramatic reduction of Satb2 expression in the transfected cerebral cortex, suggesting DSBs had occurred in the Satb2 gene with high efficiency. Furthermore, we found that Cas9 mediated targeting of the Satb2 gene induced abnormalities in axonal projection patterns, which is consistent with the phenotypes previously observed in Satb2 mutant mice. Introduction of pX330-NeuN using our procedure also resulted in the efficient disruption of the NeuN gene. Thus, our procedure combining the CRISPR/Cas9 system and in utero electroporation is an effective and rapid approach to achieve brain-specific gene knockout in vivo. PMID- 26857613 TI - Trade-off between frequency and precision during stepping movements: Kinematic and BOLD brain activation patterns. AB - The central nervous system has the ability to adapt our locomotor pattern to produce a wide range of gait modalities and velocities. In reacting to external pacing stimuli, deviations from an individual preferred cadence provoke a concurrent decrease in accuracy that suggests the existence of a trade-off between frequency and precision; a compromise that could result from the specialization within the control centers of locomotion to ensure a stable transition and optimal adaptation to changing environment. Here, we explore the neural correlates of such adaptive mechanisms by visually guiding a group of healthy subjects to follow three comfortable stepping frequencies while simultaneously recording their BOLD responses and lower limb kinematics with the use of a custom-built treadmill device. In following the visual stimuli, subjects adopt a common pattern of symmetric and anti-phase movements across pace conditions. However, when increasing the stimulus frequency, an improvement in motor performance (precision and stability) was found, which suggests a change in the control mode from reactive to predictive schemes. Brain activity patterns showed similar BOLD responses across pace conditions though significant differences were observed in parietal and cerebellar regions. Neural correlates of stepping precision were found in the insula, cerebellum, dorsolateral pons and inferior olivary nucleus, whereas neural correlates of stepping stability were found in a distributed network, suggesting a transition in the control strategy across the stimulated range of frequencies: from unstable/reactive at lower paces (i.e., stepping stability managed by subcortical regions) to stable/predictive at higher paces (i.e., stability managed by cortical regions). Hum Brain Mapp 37:1722-1737, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26857614 TI - The influence of BMI on the association between serum lycopene and the metabolic syndrome. AB - Overweight and obese individuals have an increased risk of developing the metabolic syndrome because of subsequent chronic inflammation and oxidative stress, which the antioxidant nutrient lycopene can reduce. However, studies indicate that different BMI statuses can alter the positive effects of lycopene. Therefore, the purpose of this study was to examine how BMI influences the association between serum lycopene and the metabolic syndrome. The tertile rank method was used to divide 13 196 participants, aged 20 years and older, into three groups according to serum concentrations of lycopene. The associations between serum lycopene and the metabolic syndrome were analysed separately for normal-weight, overweight and obese participants. Overall, the prevalence of the metabolic syndrome was significantly higher in the first tertile group (OR 38.6%; 95% CI 36.9, 40.3) compared with the second tertile group (OR 29.3%; 95% CI 27.5, 31.1) and the third tertile group (OR 26.6%; 95% CI 24.9, 28.3). However, the associations between lycopene and the metabolic syndrome were only significant for normal-weight and overweight participants (P0.05), even after adjusting for possible confounding variables. In conclusion, BMI appears to strongly influence the association between serum lycopene and the metabolic syndrome. PMID- 26857616 TI - Geographic Distribution of Disaster-Specific Emergency Department Use After Hurricane Sandy in New York City. AB - OBJECTIVE: We aimed to characterize the geographic distribution of post-Hurricane Sandy emergency department use in administrative flood evacuation zones of New York City. METHODS: Using emergency claims data, we identified significant deviations in emergency department use after Hurricane Sandy. Using time-series analysis, we analyzed the frequency of visits for specific conditions and comorbidities to identify medically vulnerable populations who developed acute postdisaster medical needs. RESULTS: We found statistically significant decreases in overall post-Sandy emergency department use in New York City but increased utilization in the most vulnerable evacuation zone. In addition to dialysis- and ventilator-dependent patients, we identified that patients who were elderly or homeless or who had diabetes, dementia, cardiac conditions, limitations in mobility, or drug dependence were more likely to visit emergency departments after Hurricane Sandy. Furthermore, patients were more likely to develop drug resistant infections, require isolation, and present for hypothermia, environmental exposures, or administrative reasons. CONCLUSIONS: Our study identified high-risk populations who developed acute medical and social needs in specific geographic areas after Hurricane Sandy. Our findings can inform coherent and targeted responses to disasters. Early identification of medically vulnerable populations can help to map "hot spots" requiring additional medical and social attention and prioritize resources for areas most impacted by disasters. (Disaster Med Public Health Preparedness. 2016;10:351-361). PMID- 26857615 TI - The binding capability of plasma phospholipid transfer protein, but not HDL pool size, is critical to repress LPS induced inflammation. AB - Phospholipid transfer protein (PLTP) participates in high density lipoprotein (HDL) metabolism. Increased plasma PLTP activity was observed in lipopolysaccharide (LPS) triggered acute inflammatory diseases. This study aimed to determine the exact role of PLTP in LPS induced inflammation. HDL pool size was shrunk both in PLTP deficient mice (PLTP-/-) and PLTP transgenic mice (PLTP Tg). PLTP displayed a strong protective effect on lethal endotoxemia in mice survival study. Furthermore, after LPS stimulation, the expression of pro inflammatory cytokines were increased in bone marrow derived macrophage (BMDM) from PLTP-/-, while decreased in BMDM from PLTP-Tg compared with BMDM from wild type mice (WT). Moreover, LPS induced nuclear factor kappa-B (NFkappaB) activation was enhanced in PLTP-/- BMDM or PLTP knockdown RAW264.7. Conversely, PLTP overexpression countered the NFkappaB activation in LPS challenged BMDM. Additionally, the activation of toll like receptor 4 (TLR4) induced by LPS showed no alteration in PLTP-/- BMDM. Finally, PLTP could bind to LPS, attenuate the pro inflammatory effects of LPS, and improve the cell viability in vitro. To sum up, these findings elucidated that PLTP repressed LPS induced inflammation due to extracellular LPS binding capability, and the protective effects were not related to HDL pool size in mice. PMID- 26857617 TI - Squamous cell carcinoma arising from a presacral cyst in a patient with ulcerative colitis under azathioprine and infliximab: first case report. PMID- 26857618 TI - Chronic hepatitis C virus infection and susceptibility to coronary artery disease: a three player match? PMID- 26857619 TI - Voice Modulation: A Window into the Origins of Human Vocal Control? AB - An unresolved issue in comparative approaches to speech evolution is the apparent absence of an intermediate vocal communication system between human speech and the less flexible vocal repertoires of other primates. We argue that humans' ability to modulate nonverbal vocal features evolutionarily linked to expression of body size and sex (fundamental and formant frequencies) provides a largely overlooked window into the nature of this intermediate system. Recent behavioral and neural evidence indicates that humans' vocal control abilities, commonly assumed to subserve speech, extend to these nonverbal dimensions. This capacity appears in continuity with context-dependent frequency modulations recently identified in other mammals, including primates, and may represent a living relic of early vocal control abilities that led to articulated human speech. PMID- 26857620 TI - The diversity effect in diagnostic reasoning. AB - Diagnostic reasoning draws on knowledge about effects and their potential causes. The causal-diversity effect in diagnostic reasoning normatively depends on the distribution of effects in causal structures, and thus, a psychological diversity effect could indicate whether causally structured knowledge is used in evaluating the probability of a diagnosis, if the effect were to covary with manipulations of causal structures. In four experiments, participants dealt with a quasi medical scenario presenting symptom sets (effects) that consistently suggested a specified diagnosis (cause). The probability that the diagnosis was correct had to be rated for two opposed symptom sets that differed with regard to the symptoms' positions (proximal or diverse) in the causal structure that was initially acquired. The causal structure linking the diagnosis to the symptoms and the base rate of the diagnosis were manipulated to explore whether the diagnosis was rated as more probable for diverse than for proximal symptoms when alternative causations were more plausible (e.g., because of a lower base rate of the diagnosis in question). The results replicated the causal diversity effect in diagnostic reasoning across these conditions, but no consistent effects of structure and base rate variations were observed. Diversity effects computed in causal Bayesian networks are presented, illustrating the consequences of the structure manipulations and corroborating that a diversity effect across the different experimental manipulations is normatively justified. The observed diversity effects presumably resulted from shortcut reasoning about the possibilities of alternative causation. PMID- 26857621 TI - The Law and Social Values: Medical Necessity and Criminal Prosecution. PMID- 26857622 TI - A rapid and inexpensive DNA extraction protocol for oysters. PMID- 26857623 TI - Low-dose ionizing irradiation triggers a 53BP1 response to DNA double strand breaks in mouse spermatogonial stem cells. AB - The present study aims to examine the effect of low-dose ionizing irradiation on DNA double strand breaks (DSB) in mouse spermatogonial stem cells (SSCs) and reveal the underlying pathways for the DNA repair for DSB in SSCs. Eighteen one month-old mice were divided into 6 groups and sacrificed separately at 45 minutes, 2 hours, 24 hours, 48 hours, and 72 hours after 0.1Gy X-ray irradiation (mice without receiving ionizing irradiation served as control). After perfusion fixation, testes were removed, sectioned, and followed by staining of gammaH2AX, 53BP1, Caspase 3, and promyelocytic leukemia zinc-finger (PLZF) for analysis among the different groups. The staining was observed by immunofluorescence visualized by confocal laser scanning. After low-dose irradiation, only 53BP1, but not Caspase3 or gammaH2AX was upregulated in PLZF positive SSCs within 45 minutes. The expression level of 53BP1 gradually decreased 24 hours after irradiation. Moreover, low-dose irradiation had no effect on the cell number and apoptotic status of SSCs. However other spermatogenic cells highly expressed gammaH2AX shortly after irradiation which was dramatically reduced following the events of DNA repair. It appears that low-dose ionizing irradiation may cause the DNA DSB of mouse spermatogenic cells. 53BP1, but not gammaH2AX, is involved in the DNA repair for DSB in SSCs. Our data indicates that 53BP1 plays an important role in the pathophysiological repair of DNA DSB in SSCs. This may open a new avenue to understanding the mechanisms of DNA repair of SSCs and male infertility. PMID- 26857624 TI - Using a mixed-methods approach to measure impact of a school-based nutrition and media education intervention study on fruit and vegetable intake of Italian children. AB - OBJECTIVE: The purpose of the present study was to investigate the impact of a school-based nutrition and media education intervention on the promotion of fruit and vegetable consumption to help prevent childhood obesity. DESIGN: The 10-week long intervention included sessions on nutrition education and media literacy. It also included a health communication media-based campaign workshop during which the children created posters, newsletters and video commercials related to fruits and vegetables targeted to their parents. For evaluation purposes, the study utilized a mixed-methods approach, including a quasi-experimental study (with one intervention group and one control group) and a focus group study. SETTING: Four different elementary schools in Treviso (Veneto Region of Italy) agreed to participate in the research. SUBJECTS: The target population for the study included 10-year-old Italian children and their parents. RESULTS: Data indicate that this intervention was effective for children but not for parents. Evaluation results show that the intervention was effective in significantly increasing children's fruit and vegetable intake (P<0.05) and all psychosocial determinants (P<0.05). CONCLUSIONS: The study results confirm the efficacy of a school-based health and media education intervention to address the children's obesity issue and, in particular, to increase children's fruit and vegetable intake. The study also opens a new perspective on the theoretical constructs investigated, because the development of 'ability of expression' could be considered one of the most important factors to determine the efficacy of the intervention. PMID- 26857625 TI - Admixture, Population Structure, and F-Statistics. AB - Many questions about human genetic history can be addressed by examining the patterns of shared genetic variation between sets of populations. A useful methodological framework for this purpose isF-statistics that measure shared genetic drift between sets of two, three, and four populations and can be used to test simple and complex hypotheses about admixture between populations. This article provides context from phylogenetic and population genetic theory. I review how F-statistics can be interpreted as branch lengths or paths and derive new interpretations, using coalescent theory. I further show that the admixture tests can be interpreted as testing general properties of phylogenies, allowing extension of some ideas applications to arbitrary phylogenetic trees. The new results are used to investigate the behavior of the statistics under different models of population structure and show how population substructure complicates inference. The results lead to simplified estimators in many cases, and I recommend to replace F3 with the average number of pairwise differences for estimating population divergence. PMID- 26857626 TI - Phenotypic Plasticity Promotes Balanced Polymorphism in Periodic Environments by a Genomic Storage Effect. AB - Phenotypic plasticity is known to evolve in perturbed habitats, where it alleviates the deleterious effects of selection. But the effects of plasticity on levels of genetic polymorphism, an important precursor to adaptation in temporally varying environments, are unclear. Here we develop a haploid, two locus population-genetic model to describe the interplay between a plasticity modifier locus and a target locus subject to periodically varying selection. We find that the interplay between these two loci can produce a "genomic storage effect" that promotes balanced polymorphism over a large range of parameters, in the absence of all other conditions known to maintain genetic variation. The genomic storage effect arises as recombination allows alleles at the two loci to escape more harmful genetic backgrounds and associate in haplotypes that persist until environmental conditions change. Using both Monte Carlo simulations and analytical approximations we quantify the strength of the genomic storage effect across a range of selection pressures, recombination rates, plasticity modifier effect sizes, and environmental periods. PMID- 26857627 TI - Maintenance of Membrane Integrity and Permeability Depends on a Patched-Related Protein in Caenorhabditis elegans. AB - Membrane integrity is critical for cell survival, defects of which cause pathological symptoms such as metabolic diseases. In this study, we used ethanol sensitivity of the nematode Caenorhabditis elegans to identify genetic factors involved in membrane integrity. InC. elegans, acute exposure to a high concentration (7% v/v) of ethanol changes membrane permeability, as measured by propidium iodide staining, and causes paralysis. We used the timing of complete paralysis as an indicator for alteration of membrane integrity in our genetic screen, and identified ptr-6 as a gene that confers ethanol resistance when mutated. PTR-6 is a patched-related protein and contains a sterol sensing domain. Inhibition of two PTR-encoding genes,ptr-15 and ptr-23, and mboa-1, encoding an Acyl Co-A: cholesterol acyltransferase homolog, restored ethanol sensitivity of the ptr-6 mutant, suggesting that these ptr genes and mboa-1 are involved in the maintenance of membrane integrity and permeability. Our results suggest that C. elegans can be used as a model system to identify factors involved in metabolic diseases and to screen for therapeutic drugs. PMID- 26857629 TI - Correlation between scatter radiation dose at height of operator's eye and dose to patient for different angiographic projections. AB - Studies have reported cases of radiation-induced cataract among cardiology professionals. In view of the evidence of epidemiological studies, the ICRP recommends a new threshold for opacities and a new radiation dose to eye lens limit of 20mSv per year for occupational exposure. The aim of this paper is to report scattered radiation doses at the height of the operator's eye in an interventional cardiology facility without considering radiation protection devices and to correlate these values with different angiographic projections and operational modes. Measurements were taken in a cardiac laboratory with an angiography X-ray system equipped with flat-panel detector. PMMA plates of 30*30*5cm were used with a thickness of 20cm. Measurements were taken in two fluoroscopy modes (low and normal, 15pulses/s) and in cine mode (15frames/s). Four angiographic projections were used: anterior posterior; lateral; left anterior oblique caudal (spider); and left anterior oblique cranial, with a cardiac protocol for patients weighing between 70 and 90kg. Measurements of phantom entrance dose rate and scatter dose rate were performed with two Unfors Xi plus detectors. The detector measuring scatter radiation was positioned at the usual distance of the cardiologist's eyes during working conditions. There is a good linear correlation between the kerma area product and scatter dose at the lens. Experimental correlation factors of 2.3, 12.0, 12.2 and 17.6MUSv/Gycm2 were found for different projections. PMMA entrance dose rates for low and medium fluoroscopy and cine modes were 13, 39 and 282mGy/min, respectively, for AP projection. PMID- 26857628 TI - Coalescent Inference Using Serially Sampled, High-Throughput Sequencing Data from Intrahost HIV Infection. AB - Human immunodeficiency virus (HIV) is a rapidly evolving pathogen that causes chronic infections, so genetic diversity within a single infection can be very high. High-throughput "deep" sequencing can now measure this diversity in unprecedented detail, particularly since it can be performed at different time points during an infection, and this offers a potentially powerful way to infer the evolutionary dynamics of the intrahost viral population. However, population genomic inference from HIV sequence data is challenging because of high rates of mutation and recombination, rapid demographic changes, and ongoing selective pressures. In this article we develop a new method for inference using HIV deep sequencing data, using an approach based on importance sampling of ancestral recombination graphs under a multilocus coalescent model. The approach further extends recent progress in the approximation of so-called conditional sampling distributions, a quantity of key interest when approximating coalescent likelihoods. The chief novelties of our method are that it is able to infer rates of recombination and mutation, as well as the effective population size, while handling sampling over different time points and missing data without extra computational difficulty. We apply our method to a data set of HIV-1, in which several hundred sequences were obtained from an infected individual at seven time points over 2 years. We find mutation rate and effective population size estimates to be comparable to those produced by the software BEAST. Additionally, our method is able to produce local recombination rate estimates. The software underlying our method, Coalescenator, is freely available. PMID- 26857631 TI - Severe rhabdomyolysis secondary to adenovirus infection: case report and literature review. AB - A 38-year-old male presented with renal failure in the setting of a flu-like illness. Urinalysis showed myoglobinuria and granular casts. His serum creatine phosphokinase was markedly elevated. He was diagnosed with rhabdomyolysis and was volume resuscitated with normal saline and bicarbonate-containing fluid. Workup included a respiratory viral panel which was positive for adenovirus. Other causes such as trauma, seizure, and intoxicants were excluded. He developed progressive renal failure necessitating hemodialysis. After ~ 4 weeks he recovered renal function and dialysis was discontinued. Viral-induced myopathy should be suspected in patients who present with rhabdomyolysis. PMID- 26857630 TI - Does the risk of peritoneal dialysis-associated peritonitis vary by time on treatment? AB - BACKGROUND: Early retraining of patients/caregivers at 3 months after peritoneal dialysis (PD) initiation is recommended to prevent peritonitis. We sought to better understand if the risk of peritonitis was highest early after the initiation of PD and if the risk varied by time on therapy and by organism. METHODS: Using the multicenter Canadian Baxter POET database, we studied 4,247 incident PD patients. Time on dialysis was divided into 3-month intervals over the first 2 years on PD, with 0 - 3 months serving as the reference period. After creating several organism categories (all organisms, coagulase-negative staphylococcus (CNS), Staphylococcus aureus, streptococcus, Gramnegative, culture negative, and yeast), time to first peritonitis was analyzed by Kaplan-Meier analysis and using smooth hazard plots. The risk of peritonitis for each of these categories over time was then analyzed in a multivariable model after adjusting for potential confounding variables. RESULTS: The overall risk of peritonitis (all organisms) was greatest in the first 3 months on PD compared with all subsequent 3-month intervals (p = 0.001). Organism-specific analyses revealed an increased risk of culture-negative peritonitis in the first 3 months (p < 0.001) but no increased risk of CNS peritonitis or any of the other pre-specified organism categories. CONCLUSIONS: The overall risk of peritonitis was greatest in the first 3 months on PD and was largely driven by an increased risk of culture negative peritonitis but not by CNS. Better understanding of this increased early peritonitis risk is warranted in order to develop strategies aimed at its prevention. PMID- 26857633 TI - Simple radiographic assessment of bone quality is associated with loss of surgical fixation in patients with proximal humeral fractures. AB - AIM: This study aimed to determine if the ratio of cortical thickness to shaft diameter of the humerus, as measured on a simple anterior-posterior shoulder radiograph, is associated with surgical fixation failure. PATIENTS AND METHODS: 64 consecutive fractures in 63 patients (mean age 66.1 years, range 35-90) operated with surgical fixation between March 2011 and July 2014 using PERI-LOC locking plate and screws (Smith and Nephew, UK) were identified. Predictors of bone quality were measured from preoperative radiographs, including ratio of the medial cortex to shaft diameter (medial cortical ratio, MCR). Loss of fixation (displacement, screw cut out, or change in neck-shaft angle >4 degrees) was determined on follow-up radiographs. RESULTS: Loss of fixation occurred in 14 patients (21.9%) during the follow up. Patients were older in the failure group 72.8 vs. 64.2 years (p=0.007). The MCR was significantly lower in patients with failed fixation 0.170 vs 0.202, p=0.019. Loss of fixation is three times more likely in patients with a MCR <0.16 (41% vs. 14%, p=0.015). Increased fracture parts led to increased failure rate (p=0.0005). CONCLUSION: Medial cortex ratio is significantly associated with loss of surgical fixation and may prove to be a useful adjunct for clinical decision making in patients with proximal humeral fractures. PMID- 26857632 TI - Increased infection risk after hip hemiarthroplasty in institutionalized patients with proximal femur fracture. AB - In patients undergoing hip hemiarthroplasty (HHA) secondary to proximal femur fracture, acute periprosthetic joint infection (PJI) is one of the most important complications. We have detected an increased risk of PJI in chronic institutionalized patients (CIPs), and a higher number of early postoperative infections are caused by Gram-negative bacteria (GNB), not covered by the current prophylaxis (cefazolin in noninstitutionalized patients (NIPs) and cotrimoxazole in CIPs). We sought to compare infection characteristics between NIPs and CIPs, analyzing predisposing factors, causative pathogens, and antibiotic prophylaxis related microbiological characteristics. We performed a retrospective review of our prospective institutional database to identify all patients consecutively admitted for HHA to treat proximal femur fracture at our centre between 2011 and 2013. PJI was diagnosed in 21 of 381 (5.51%) patients, with 10 of 105 (9.52%) in the CIP group and 11 of 276 (3.99%) in the NIP group, and statistical significance was achieved. GNB accounted for PJI in 14 (66.67%) patients. We detected a single case of methicillin-resistant Staphylococcus aureus (MRSA) infection in the NIP group. We confirm a higher risk of acute PJI among institutionalized patients, commonly caused by Gram-negative microorganisms, which are not covered by the current prophylaxis. New prophylactic strategies should be investigated in order to reduce this problem. PMID- 26857634 TI - Moderate Ischemic Mitral Regurgitation After Posterolateral Myocardial Infarction in Sheep Alters Left Ventricular Shear but Not Normal Strain in the Infarct and Infarct Borderzone. AB - BACKGROUND: Chronic ischemic mitral regurgitation (CIMR) is associated with poor outcome. Left ventricular (LV) strain after posterolateral myocardial infarction (MI) may drive LV remodeling. Although moderate CIMR has been previously shown to affect LV remodeling, the effect of CIMR on LV strain after posterolateral MI remains unknown. We tested the hypothesis that moderate CIMR alters LV strain after posterolateral MI. METHODS: Posterolateral MI was created in 10 sheep. Cardiac magnetic resonance imaging with tags was performed 2 weeks before and 2, 8, and 16 weeks after MI. The left and right ventricular volumes were measured, and regurgitant volume indexed to body surface area (regurgitant volume index) was calculated as the difference between left ventricle and right ventricle stroke volumes divided by body surface area. Three-dimensional strain was calculated. RESULTS: Circumferential strain (Ecc) and longitudinal strain (Ell) were reduced in the infarct proper, MI borderzone, and remote myocardium 16 weeks after MI. In addition, radial circumferential (Erc) and radial longitudinal (Erl) shear strains were reduced in remote myocardium but increased in the infarct and borderzone 16 weeks after MI. Of all strain components, however, only Erc was affected by regurgitant volume index (p = 0.0005). There was no statistically significant effect of regurgitant volume index on Ecc, Ell, Erl, or circumferential longitudinal shear strain (Ecl). CONCLUSIONS: Moderate CIMR alters radial circumferential shear strain after posterolateral MI in sheep. Further studies are needed to determine the effect of shear strain on myocyte hypertrophy and the effect of mitral repair on myocardial strain. PMID- 26857635 TI - Bentall Procedure: A Systematic Review and Meta-Analysis. AB - BACKGROUND: The Bentall procedure is considered the gold standard in the treatment of patients requiring aortic root replacement. An up-to-date overview of outcomes after the Bentall procedure is lacking. METHODS: We conducted a systematic review and meta-analysis of characteristics of and long-term outcome after the Bentall procedure with a mechanical valve prosthesis. Pooling was performed using the inverse variance method within a random-effects model. Outcome events are reported as linearized occurrence rates (percentage per patient year) with 95% confidence intervals. RESULTS: In total, 46 studies with 7,629 patients (mean age, 50 years; 76% men) were selected. Pooled early mortality was 6% (422 patients). During a mean follow-up of 6 years (49,175 patient-years), the annual linearized occurrence rate for late mortality was 2.02% (1.77%- 2.31%; 892 patients), for aortic root reoperation it was 0.46% (0.36%-0.59%), for hemorrhage it was 0.64% (0.47%-0.87%), for thromboemboli it was 0.77% (0.60%-1.00%), for endocarditis it was 0.39% (0.33%-0.46%), and for major adverse valve-related events it was 2.66% (2.17%-3.24%). Operations performed in more recent years were associated with lower rates of aortic root reoperation (beta = -0.452; p = 0.015). CONCLUSIONS: This systematic review illustrates that rates of aortic root reoperation after the Bentall procedure have decreased over the years. However, late mortality, major bleeding, and thromboembolic complications remain a concern. This report may be used to benchmark the potential therapeutic benefit of novel surgical approaches, such as valve-sparing aortic root replacement. PMID- 26857636 TI - Extraanatomic Bypass to Supraceliac Abdominal Aorta for Complex Thoracic Aortic Obstruction. AB - BACKGROUND: The standard surgical treatment of coarctation of the aorta is through a left posterolateral thoracotomy. However, when a concomitant cardiac procedure is required or the conventional approach is not possible or is hazardous, extraanatomic bypass to the supraceliac abdominal aorta may be advantageous. We discuss our technique and report the long-term results. METHODS: Between January 1986 and January 2015, 25 patients (16 males, 9 females) underwent extraanatomic bypass to the supraceliac abdominal aorta for various lesions of the arch and the descending thoracic aorta. Extraanatomic bypass to the supraceliac abdominal aorta was performed for patients in whom balloon dilatation was not feasible due to associated arch hypoplasia (n = 9), long segment thoracic aorta narrowing due to nonspecific aortoarteritis (n = 3), or isolated long-segment coarctation of the aorta (n = 3). Patients who needed concomitant cardiac procedures, such as aortic valve replacement (n = 4), ascending aortic aneurysm repair (n = 2), or coronary artery bypass grafting (n = 1), and in whom balloon dilatation had failed, also underwent extraanatomic bypass to the supraceliac abdominal aorta. Extraanatomic bypass was also performed in 3 patients with recurrent coarctation after surgical repair and in whom balloon dilation was not feasible or unsuccessful. RESULTS: There were no early or late deaths. The peak-to-peak gradients between the upper limb and the lower limb decreased from 59.3 +/- 16.3 mm Hg to 2.0 +/- 2.8 mm Hg (p < 0.0001). The mean follow-up was 96.6 +/- 92.6 months (range, 1 to 240 months; median, 54 months). Doppler interrogation of the lower limb arterial system after a mean follow-up of 86.4 +/- 85.2 months showed an unobstructed flow pattern. The ankle brachial pressure index improved from a preoperative value of 0.60 +/- 0.07 to 1.04 +/- 0.11 (p < 0.0001). Systolic blood pressure decreased significantly compared with preoperative values (153.9 +/- 18.9 vs 122.8 +/- 10.2, p < 0.0001). Three patients continued to receive antihypertensive medication due to persistent mild hypertension. CONCLUSIONS: Extraanatomic bypass to the supraceliac abdominal aorta provides effective palliation for complex aortic obstructions. It is easy and quick to perform, avoids fatal complications, and is well tolerated in all age groups. PMID- 26857637 TI - Non-Fontan Adult Congenital Heart Disease Transplantation Survival Is Equivalent to Acquired Heart Disease Transplantation Survival. AB - BACKGROUND: As a result of improved diagnostic methods, medical treatment, surgical correction, and palliation in childhood, there is a growing number of adult patients with congenital heart disease (CHD) who may experience heart failure and subsequently require heart transplantation (HT). Because of complex anatomy, previous operations, and frequently increased pulmonary vascular resistance (PVR), these patients represent a group with a higher risk of early mortality after transplantation. METHODS: From May 1999 to December 2014, our institution performed 25 HTs in adult patients with end-stage CHD. We present our data and outcomes of transplantation in this group. RESULTS: The median age at transplantation was 38 years (range, 18.4-53.7 years). Survival was 88% at 30 days, 88% at 1 year, and 77% at 5 years. We identified long donor heart ischemic time (>4 hours) as an important risk factor for early mortality. There was no significant difference in the survival of patients undergoing transplantation for CHD and patients undergoing transplantation for other diagnoses. CONCLUSIONS: With careful donor and recipient selection, adults with end-stage CHD undergoing HT can achieve excellent early and midterm survival, comparable to the survival of patients who undergo transplantation for other diagnoses. PMID- 26857638 TI - Vulnerability of Coronary Circulation After Norwood Operation. AB - BACKGROUND: We hypothesized that the myocardial oxygen supply-demand balance is impaired in patients after a Norwood procedure and that an abnormal oxygen supply demand balance is associated with pronounced activation of the renin-angiotensin aldosterone system and worse clinical outcome after this procedure. METHODS: To investigate the myocardial oxygen supply-demand balance, the subendocardial viability ratio (SEVR) was measured in 29 hypoplastic left heart syndrome patients after the Norwood procedure, in 27 patients with pulmonary atresia whose pulmonary blood flow was supplied from the aortopulmonary (AP) shunt, and in 30 control patients who were considered to have normal biventricular circulation. The SEVR in Norwood (0.57 +/- 0.18) and AP shunt (0.66 +/- 0.10) patients was significantly reduced compared with that in controls (0.94 +/- 0.25, p < 0.001 vs Norwood and AP shunt). RESULTS: After controlling for heart rate, the SEVR was significantly lower in Norwood than in AP shunt patients (p < 0.001). Importantly, the SEVR was significantly lower in Norwood patients with poor clinical outcomes (cardiac arrest before second-stage operation, progressive tricuspid regurgitation, or reduction of ejection fraction <0.35) than in the remaining Norwood patients (0.51 +/- 0.12 vs 0.69 +/- 0.22, p < 0.01). An SEVR of less than 0.52 had a more than 76% probability of having a poor outcome (p < 0.05). Furthermore, a lower SEVR was significantly correlated with more pronounced renin-angiotensin-aldosterone system activation and elevated natriuretic peptides in serum. Multiple regression analysis revealed that increased aortic stiffness and a smaller neoaorta relative to the native descending aorta were independent determinants of reduced SEVR. CONCLUSIONS: Myocardial oxygen supply-demand imbalance is intrinsic to Norwood circulation but may be improved by technical refinement of aortic reconstruction or afterload reducing medication with renin-angiotensin-aldosterone system blockade. PMID- 26857639 TI - Ischemic Conditioning of the Stomach in the Prevention of Esophagogastric Anastomotic Leakage After Esophagectomy. AB - Esophagectomy with esophagogastric anastomosis is a major procedure, and its most feared complication is anastomotic leakage. Ischemic conditioning of the stomach is a method used with the aim of reducing the risk of leakage. It consists of partial gastric devascularization through embolization or laparoscopy followed by esophagectomy and anastomosis at a second stage, thus providing the time for the gastric conduit to adapt to the acute ischemia at the time of its formation. This review analyzes the information from all currently available experimental and clinical studies with the purpose of assessing the current role of the technique and to provide future recommendations. PMID- 26857640 TI - Phytochemicals in the Fight Against Cancer. AB - Phytochemicals are chemical compounds from fruits, vegetables, or grains and they have been used to treat various diseases for thousands of years. More than one million people in the United States get cancer each year. Although recent advances in medicine have improved the outcomes for cancer patients, there is still a need for novel approaches in the fight against cancer. One such approach that has shown promise in recent years is the use of phytochemicals alone or as synergistic agents. In this review, we will discuss the use of phytochemicals as therapeutic agents against cancer with an emphasis on apple extract. PMID- 26857641 TI - Detection and Analysis of Wnt Pathway Related lncRNAs Expression Profile in Lung Adenocarcinoma. AB - Studies have shown that the expression profile of Wnt signaling pathway is very important in lung adenocarcinoma (LAD) and some lncRNAs can regulate the expression of key molecules of Wnt pathway. However, Wnt pathway related lncRNAs are not systematically analyzed and detected in lung adenocarcinoma. We used a high-throughput microarray to compare the lncRNA expression profiles in LAD and corresponding normal tissue (NT) samples. Several candidate Wnt pathway related lncRNAs were verified by real-time quantitative reverse transcription polymerase chain reaction (PCR) analysis. We found that 232 Wnt pathway related lncRNAs were obviously expressed (>=2-fold change) in lung adenocarcinoma samples and 13 Wnt pathway related lncRNAs were aberrantly expressed in lung adenocarcinoma compared with matched histologically normal lung tissues by qPCR. Among these, RP11 181G12.2 and RP11-89 K21.1 were the most aberrantly expressed lncRNAs. Our study ascertained the expression of Wnt pathway related lncRNAs in lung adenocarcinoma. The results revealed that many Wnt pathway related lncRNAs were differentially expressed in lung adenocarcinoma tissues, suggesting that they may play a key role in tumor development. PMID- 26857642 TI - Recurrent umbilical or epigastric hernia during and after pregnancy: A nationwide cohort study. AB - BACKGROUND: Umbilical and epigastric (umb/epi) hernia repairs are performed commonly in fertile female patients. Recent studies suggest mesh repair to be superior to suture repair; however, evidence is lacking concerning the optimal treatment of umb/epi hernias in female patients who might wish future pregnancies. The aim of this study was to compare the cumulative recurrence rate after mesh versus suture repair of umb/epi hernia in female patients subsequently becoming pregnant. METHODS: This retrospective nationwide cohort study included female patients who underwent primary umb/epi hernia repair and subsequently became pregnant between 2007 and 2013. The follow-up began at first day of pregnancy and ended May 2015. Data were obtained from the Danish Ventral Hernia Database, Medical Birth Registry, and National Patient Registry. Patients with recurrence before pregnancy were excluded. RESULTS: In total, 224 patients were analyzed. The median follow-up was 3.8 years (range 0.1-8.1). The cumulative recurrence rate was 16.3% after mesh repair and 10.9% after suture repair, P = .299. Univariate Cox regression analysis (mesh repair hazard ratio 1.63, 95% confidence interval 0.71-3.72, P = .249) and multivariate analysis adjusted for body mass index and hernia defect size (mesh repair hazard ratio 2.77, confidence interval 0.98-7.85, P = .055) likewise showed no significant difference in the risk of recurrence when we compared mesh and suture repair. CONCLUSION: Contrary to findings in the general operative patient, mesh repair was not associated with a lesser risk of recurrence compared with suture repair for treatment of umb/epi hernia in female patients with subsequent pregnancy. PMID- 26857643 TI - A Colloidal Stability Assay Suitable for High-Throughput Screening. AB - A library of 32 polystyrene copolymer latexes, with diameters ranging between 53 and 387 nm, was used to develop and demonstrate a high-throughput assay using a 96-well microplate platform to measure critical coagulation concentrations, a measure of colloidal stability. The most robust assay involved an automated centrifugation-decantation step to remove latex aggregates before absorbance measurements, eliminating aggregate interference with optical measurements made through the base of the multiwell plates. For smaller nanoparticles (diameter <150 nm), the centrifugation-decantation step was not required as the interference was less than with larger particles. Parallel measurements with a ChemiDoc MP plate scanner gave indications of aggregation; however, the results were less sensitive than the absorbance measurements. PMID- 26857644 TI - [Spontaneous rupture of the imperforate hymen in two newborns]. AB - Imperforate hymen is the most frequent congenital malformation of the female genital tract and usually remains asymptomatic until puberty. The diagnosis of this malformation is rarely made at birth and surgical treatment is often by hymenotomy. However, spontaneous rupture of the imperforate hymen is possible but is very rare. We report two cases of imperforate hymen revealed by mucocolpos at birth. Ultrasound examination does not objectify hydrocolpos or hydrometrocolpos. Spontaneous rupture of the imperforate hymen was observed respectively in the 4th and 7th day of life with a satisfactory result at 1 month of age. Screening for the imperforate hymen must be systematic at birth to offer early hymenotomy if the spontaneous rupture is not adequate and prevent serious complications of the disease at puberty. PMID- 26857645 TI - [Perinatal asphyxia and acute renal insufficiency in Ouagadougou]. AB - AIM: This study aimed to analyze acute renal failure in perinatal asphyxia (PNA) of term newborns in a sub-Saharan urban health center. PATIENTS AND METHODS: The study was prospective, conducted from 1st June to 30th November 2013 on term newborns hospitalized at the centre hospitalier universitaire pediatrique Charles de-Gaulle for PNA. Renal insufficiency (RI) was defined by a serum creatinine greater than or equal to 90 MUmol/L. RESULTS: Eighty-five PNA cases were included, or 19.8% of newborns hospitalized in the study period. The sex ratio was 2.1. Thirty-eight newborns (44.7%) had RI. Their creatinine averaged 153.8+/ 96.6 MUmol/L. Twenty-six of 38 (68.4%) had brain damage in Sarnat stage 2 and 12 (31.6%) stage 3. Twelve newborns with RI (31.6%) had seizures. Transfontanellar echography revealed an abnormality in 30 cases (78.9%) of RI. Of the 38 newborns with renal failure, albuminuria was found in 21 cases (65.2%) and leukocyturia in 28 cases (73.7%). Renal function improved in 86.1% of cases. Newborns with initially normal serum creatinine had no RI during hospitalization. Six newborns (7.1%) died. CONCLUSION: This study showed that acute RI is common during PNA most particularly in newborns with severe neurological impairment. In our context, earlier support for women in labor could help prevent PNA and therefore newborn acute RI. PMID- 26857646 TI - Stratification of aggressive prostate cancer from indolent disease-Prospective controlled trial utilizing expression of 11 genes in apparently benign tissue. AB - BACKGROUND: The aim of the study was to evaluate the diagnostic power of molecular markers in men with a clinical suspicion of prostate cancer (PCa) using apparently benign areas as targeted by magnetic resonance imaging (MRI). METHODS: In the study, 99 consecutive men with clinical suspicion of PCa in a prospective controlled trial (IMPROD, NCT01864135) were included. In addition to 12-core systematic and MRI-targeted biopsies, cores from normal-appearing prostate areas, based on clinical examination, ultrasound, and biparametric prostate MRI, were obtained. The RNA transcript levels of ACSM1, AMACR, CACNA1D, DLX1, KLK3, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1 were measured with quantitative reverse-transcription polymerase chain reaction. RESULTS: Of the 99 men, 69 were diagnosed with PCa, 31 with primary Gleason pattern 3 and 38 with primary Gleason 4 or 5. TDRD1 messenger RNA (mRNA) levels were 1.3 times higher (P = 0.029) and the presence of TMPRSS2-ERG mRNAs more frequent in biopsies from men diagnosed with PCa (27/69, 39%) than in men without (5/30, 16%) (P = 0.035). The 2 markers identified aggressive PCa defined as Gleason sum>=7 at biopsy: median TDRD1 mRNA level was 1.4 higher (P = 0.005) and TMPRSS2-ERG expression more frequent (P<0.001) in high-grade cancer. A multivariate analysis of mRNA expression of 11 candidate genes combined with KLK3, serum prostate-specific antigen (PSA), percentage-free PSA, and prostate volume improved the discrimination between aggressive and nonaggressive PCa (area under the curve = 0.77) compared with the use of the candidate genes or clinical parameters alone. However, serum PSA, percentage-free PSA, and prostate volume resulted in the best discrimination between non-organ-confined PCa (T3) from organ-confined PCa (T2) and healthy prostate (area under the curve = 0.86). CONCLUSIONS: Of the 11 studied genes, TDRD1 and TMPRSS2-ERG were able to statistically significantly differentiate men with PCa from men without it as single markers. However, a multivariate analysis using 15 features outperformed each individual marker in identifying aggressive PCa. PMID- 26857647 TI - Bowel Perforation During Peritoneal Dialysis Catheter Placement. AB - Interventional nephrologists and radiologists place peritoneal dialysis catheters using the percutaneous fluoroscopic technique in both the inpatient and outpatient setting. Nephrologists caring for such patients may have to diagnose and manage the complications resulting from these procedures. Abdominal pain can occur following peritoneal dialysis catheter placement when the local and systemic analgesia wears off. However, abdominal pain with hypotension is suggestive of a serious complication. Bleeding into the abdomen and perforation of the colon or bladder should be considered in the differential diagnosis. In the case reported here, the peritoneogram showed contrast in the bowel, and correct interpretation by the interventionist would have prevented this complication. The characteristic pattern of peritoneogram images in this case will guide interventionists to avoid this complication, and the discussion of the differential diagnosis and management will assist nephrologists in taking care of such patients. PMID- 26857649 TI - Giant idiopathic pancolonic varices - a rare entity. PMID- 26857650 TI - Genetic variants of mannose-binding lectin 2 gene influence progression and prognosis of patients with hepatitis B virus infection in China. AB - AIM: Mannose-binding lectin (MBL) is a member of the calcium-dependent collectin family involved in the innate immune system that mediates phagocytosis and activates complement by binding to carbohydrate motifs. We studied allele and haplotype frequencies of -221C/G and codon 54G/A in MBL2 gene to reveal their relationship with the developing and progression of hepatitis B virus (HBV) related liver diseases. METHODS: This study was performed in 171 healthy controls, 133 chronic hepatitis B (CHB) patients, 97 patients with HBV-related liver cirrhosis (LC) and 334 HBV-related hepatocellular carcinoma (HCC) patients. The genotypes of these two polymorphisms in these subjects were detected using polymerase chain reaction-ligation detection reaction (PCR-LDR) method. Stratification analyses by clinical characteristics and survival analysis of HCC patients were also performed according to their genotypes. RESULTS: The genotype and allele frequencies at codon 54 manifested a significant difference between healthy controls and patients with progressive HBV-related liver diseases, especially liver cirrhosis. Allele A appeared to have protective effect from developing LC and HCC compared with G allele. The percentages of the patients with G allele at -221C/G increased in HBV-related disease groups. When combined together as a haplotype, lower haplotype AC frequency was associated with a decreased risk for the progression of HBV-related liver diseases and HCC developing. Furthermore, HCC patients with G allele at codon 54 showed to have better survival than those with A allele. CONCLUSION: These results indicated that polymorphisms in MBL2 gene may influence susceptibility, progression and prognosis of HBV-related liver diseases. PMID- 26857648 TI - Detection and Clinical Patterns of Nephron Hypertrophy and Nephrosclerosis Among Apparently Healthy Adults. AB - BACKGROUND: Even among ostensibly healthy adults, there is often mild pathology in the kidney. The detection of kidney microstructural variation and pathology by imaging and the clinical pattern associated with these structural findings is unclear. STUDY DESIGN: Cross-sectional (clinical-pathologic correlation). SETTING & PARTICIPANTS: Living kidney donors at Mayo Clinic (Minnesota and Arizona sites) and Cleveland Clinic 2000 to 2011. PREDICTORS: Predonation kidney function, risk factors, and contrast computed tomographic scan of the kidneys. These scans were segmented for cortical volume and medullary volume, reviewed for parenchymal cysts, and scored for kidney surface roughness. OUTCOMES: Nephrosclerosis (glomerulosclerosis, interstitial fibrosis/tubular atrophy, and arteriosclerosis) and nephron size (glomerular volume, mean profile tubular area, and cortical volume per glomerulus) determined from an implantation biopsy of the kidney cortex at donation. RESULTS: Among 1,520 living kidney donors, nephrosclerosis associated with increased kidney surface roughness, cysts, and smaller cortical to medullary volume ratio. Larger nephron size (nephron hypertrophy) associated with larger cortical volume. Nephron hypertrophy and larger cortical volume associated with higher systolic blood pressure, glomerular filtration rate, and urine albumin excretion; larger body mass index; higher serum uric acid level; and family history of end-stage renal disease. Both nephron hypertrophy and nephrosclerosis associated with older age and mild hypertension. The net effect of both nephron hypertrophy and nephrosclerosis associating with cortical volume was that nephron hypertrophy diminished volume loss with age-related nephrosclerosis and fully negated volume loss with mild hypertension-related nephrosclerosis. LIMITATIONS: Kidney donors are selected on health, restricting the spectrum of pathologic findings. Kidney biopsies in living donors are a small tissue sample leading to imprecise estimates of structural findings. CONCLUSIONS: Among apparently healthy adults, the microstructural findings of nephron hypertrophy and nephrosclerosis differ in their associations with kidney function, macrostructure, and risk factors. PMID- 26857651 TI - A QMRA Model for Salmonella in Pork Products During Preparation and Consumption. AB - As part of a quantitative microbiological risk assessment (QMRA) food chain model, this article describes a model for the consumer phase for Salmonella contaminated pork products. Three pork products were chosen as a proxy for the entire pork product spectrum: pork cuts, minced meat patties, and fermented sausages. For pork cuts cross-contamination is considered the most important process and therefore it is modeled in detail. For minced meat, both cross contamination and undercooking are the relevant processes. For those commodities bacterial growth during transport and storage is also modeled. Fermented sausages are eaten raw and the production may be defective. Variability between consumers' behavior and the impact of variability between production processes at the farm and abattoir are taken into account. Results indicate that Salmonella levels on products may increase significantly during transport and storage. Heating is very efficient at lowering concentrations, yet cross-contamination plays an important role in products that remain contaminated. For fermented sausage it is found that drying is important for Salmonella reduction. Sensitivity analysis revealed that cross- contamination factors "knife cleaning" and "preparation of a salad" are important parameters for pork cuts. For minced meat cleaning of the board, salad consumption, refrigerator temperature, and storage time were significant. PMID- 26857652 TI - Antidepressant-like Effect of Insulin in Streptozotocin-induced Type 2 Diabetes Mellitus Rats. AB - This study evaluated the antidepressant-like effect of insulin compared to sertraline and a combination of insulin and sertraline in streptozotocin (STZ) induced type 2 diabetes mellitus (T2DM) rats submitted to the forced swim test (FST). Male Wistar rats were daily treated for 21 days with insulin (1 or 2 IU/kg, i.p.), with the selective serotonin reuptake inhibitor (SSRI), sertraline (10 mg/kg, i.p.), or with a combination of insulin (1 or 2 IU/kg, i.p.) and sertraline (10 mg/kg, i.p.) and submitted to the FST. We also evaluated the water and food intake, urine volume and weight gain of the rats. Rats treated with STZ showed impaired glucose tolerance. Chronic treatment with sertraline showed an antidepressant-like effect in non-diabetic and diabetic rats. Furthermore, sertraline promoted lower weight gain in diabetic rats. Insulin reduced the immobility behaviour in T2DM rats with impaired glucose tolerance. In conclusion, our results showed that insulin has an antidepressant-like effect comparable to that of sertraline. Sertraline is effective as an antidepressant and reduces weight gain, which reinforces its superiority over other SSRIs in the treatment of major depression disorder in patients with T2DM. PMID- 26857653 TI - [Building the Spanish primary care in a changing Europe]. PMID- 26857654 TI - [NSAID and gastrointestinal risk]. PMID- 26857657 TI - Clinical adherence to thrombophilia screening guidelines at a major tertiary care hospital. AB - Essentials Thrombophilia screening has significantly increased but has limited clinical utility. We evaluated the positive rate of thrombophilia screening and adherence to published guidelines. Both the positive rate for thrombophilia screening and the adherence to guidelines were low. Guidance implementation is essential to improve current thrombophilia screening practice. SUMMARY: Background Thrombophilia screening is widely performed but provides limited clinical utility in managing patients predisposed to venous thromboembolism. Although guidelines to limit testing have been published, adherence to those guidelines in the outpatient clinical setting has not been assessed. Objective To evaluate outpatient thrombophilia screening practices at a tertiary academic medical center. Methods We performed a retrospective review of the electronic medical records and a computational analysis of thrombophilia tests collected during a 3-year period (August 2010 to June 2013) at a large teaching hospital. Our primary outcome measures were positive diagnostic yield for thrombophilia and clinician adherence to published thrombophilia screening guidelines in the outpatient setting. Results and Conclusions We found a positive diagnostic yield of 13.8% (95% confidence interval 12.3% to 15.3%) for outpatient thrombophilia screening at our institution. Of the screening tests requiring a second confirmatory assay for definitive diagnosis, only 12% (95% confidence interval 10.3% to 13.7%) were appropriately obtained. We also observed that 73% of patients in our electronic medical record review were inappropriately tested based on existing screening guideline criteria. When parsed by specialty, we identified that hematologists had a higher adherence rate to guideline criteria than do physicians from other specialties. Our study confirms low adherence to thrombophilia screening guidelines across disciplines and indicates the need for continued clinician education. PMID- 26857656 TI - Liposomes as potential masking agents in sport doping. Part 1: analysis of phospholipids and sphingomyelins in drugs and biological fluids by aqueous normal phase liquid chromatography-tandem mass spectrometry. AB - In the present work, aqueous normal-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), in different acquisition modes, was employed for the direct analysis and profiling of nine phospholipid classes (phosphatidic acids, phosphatidylserines, phosphatidylethanolamines, lysophosphatidylethanolamines, phosphatidylglycerols, phosphatidylinositols, phosphatidylcholines, lysophosphatidylcholines, and sphingomyelins) in biological and pharmaceutical matrices. After chromatographic separation by a diol column, detection and elucidation of phospholipid and sphingomyelin classes and molecular species were performed by different scan acquisition modes. For screening analysis, molecular ions [M + H]+ were detected in positive precursor ion scan of m/z 184 for the classes of phosphatidylcholines, lyso-phosphatidylcholines and sphingomyelins; while phosphatidylethanolamines and lyso phosphatidylethanolamines were detected monitoring neutral loss scan of 141 Da; and phosphatidylserines detected using neutral loss scan of 184 Da. Molecular ions [M-H]- were instead acquired in negative precursor ion scan of m/z 153 for the classes of phosphatidic acids and phosphatidylglycerols; and of m/z 241 for the phosphatidylinositols. For the identification of the single molecular species, product ion scan mass spectra of the [M + HCOO]- ions for phosphatidylcholines and [M + H]+ ions for the other phospholipids considered were determined for each class and compared with the fragmentation pattern of model phospholipid reference standard. By this approach, nearly 100 phospholipids and sphingomyelins were detected and identified. The optimized method was then used to characterize the phospholipid and sphingomyelin profiles in human plasma and urine samples and in two phospholipid-based pharmaceutical formulations, proving that it also allows to discriminate compounds of endogenous origin from those resulting from the intake of pharmaceutical products containing phospholipidic liposomes. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26857658 TI - Elastography of shear wave speed imaging for the evaluation of liver fibrosis: A meta-analysis. AB - AIM: A meta-analysis was carried out to assess the accuracies of shear wave speed imaging (SWSI) in predicting significant fibrosis (stages F2-4) and cirrhosis (stage F4). METHODS: A review was performed of relevant studies published until October 2015. A bivariate binomial model was used to combine the sensitivity, specificity, and the area under the summary receiver operating characteristic (AUC), and 95% confidence intervals were derived to indicate the diagnostic accuracy of imaging modalities. RESULTS: In total, 10 studies with 2182 patients were included in the analysis. The sensitivity, specificity, and AUC (with 95% confidence intervals) of SWSI were: 0.84 (0.81-0.87), 0.83 (0.77-0.88), and 0.88 (0.85-0.90) for significant fibrosis, respectively; and 0.80 (0.66-0.89), 0.93 (0.88-0.96), and 0.95 (0.92-0.96) for cirrhosis, respectively. When SWSI was compared with well-evaluated transient elastography, the AUCs for the prediction of significant fibrosis were 0.93 and 0.86, respectively. The AUCs for the prediction of cirrhosis were both 0.94. CONCLUSION: Shear wave speed imaging is a trustworthy tool for staging hepatic fibrosis, with a high combination of sensitivity and specificity. Compared with transient elastography, SWSI showed better diagnostic performance for the prediction of significant fibrosis. PMID- 26857655 TI - The transcriptional coregulator MAML1 affects DNA methylation and gene expression patterns in human embryonic kidney cells. AB - Mastermind-like 1 (MAML1) is a transcriptional coregulator that has been associated with early development of many systems such as neuronal, muscular and urogenital. The present study aimed to explore the genome wide effects of MAML1 on DNA methylation and RNA expression in human embryonic kidney cells. Infinium HumanMethylation450 BeadChip Illumina array, methylation-sensitive high resolution melt technique, Chip Analysis Methylation Pipeline and RNA profiling approaches were used to study MAML1 effects on the epigenome. We found that 11802 CpG sites were differentially methylated in MAML1-expressing cells while only 225 genes were differentially expressed. MAML1 overexpression induced more global differential hypermethylation than hypomethylation changes. In addition, the differentially methylated regions were mapped predominantly to 3'untranslated regions, intragenic regions and gene bodies and to a lesser extent to gene regulatory sequences. Gene ontology analysis revealed that the differentially changed genes (including HOXC11, HTATIP2, SLFN12 and SOX11) are involved in the regulation of urogenital system development, cell adhesion and embryogenesis. This study is the first report that shows the global effect of a single coregulator on DNA methylation and gene expression. Our results stress and support the effects of transcriptional coregulators on the cell methylome. PMID- 26857660 TI - Conventional and Cellular Atypical Lipomas of the Hand and Forearm: A Report of 9 Cases. AB - PURPOSE: To report a case series of atypical lipomas of the hand and forearm and review the literature to define the clinical presentation, surgical approach, and postoperative complications including recurrence. METHODS: All cases of atypical lipomas of the hand and forearm treated by the author between 1994 and 2010 were retrospectively reviewed. The charts were reviewed for age, gender, tumor site, symptoms, preoperative studies, tumor size, type of surgical excision, and postoperative complications including recurrence. RESULTS: Nine cases were identified. All patients were middle-aged adults with a mean age of 55 years (range, 40-65 years). There were 5 women and 4 men. All patients presented with a single, painless, enlarging mass in either the palm or the volar forearm. Magnetic resonance imaging showed the tumors to be hyperintense on T1- and hypointense on T2-weighted images. All patients had marginal excision of the tumor. Histologically, 5 tumors were conventional, and 4 tumors were cellular atypical lipomas. The mean follow-up was 10 years (range, 6-16 years). There was no evidence of recurrence by clinical examination at final follow-up. CONCLUSIONS: The results of the current series and a review of the literature suggest that atypical lipomas of the hand and forearm may have a more benign behavior than atypical lipomas of other anatomical sites. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 26857659 TI - Structural studies of the C-terminal tail of polycystin-2 (PC2) reveal insights into the mechanisms used for the functional regulation of PC2. AB - Mutations in polycystin-2 (PC2) lead to autosomal dominant polycystic kidney disease (ADPKD). The molecular mechanism linking mutations in PC2 and the pathogenesis of ADPKD is not well understood. Therefore, understanding the functional regulation of PC2 and its interaction with other proteins under both physiological and pathogenic conditions is important for elucidating the disease mechanism and identifying potential molecular targets for treatment. Normally, PC2 functions as a calcium-permeable channel whose activity is regulated by calcium binding to the C-terminal domain of PC2 (PC2 Cterm). The PC2 Cterm is also involved in the PC2 channel assembly and hetero-oligomerization with other binding partners in cells. Different functional domains of the PC2 Cterm have been studied using structural approaches. Within the PC2 Cterm, there is a calcium-binding EF-hand domain, crucial for the calcium-dependent activity of the PC2 channel. Downstream of the EF-hand domain lies a coiled-coil region, which is involved in the assembly and hetero-interaction of the PC2 protein. The PC2 Cterm can form an oligomer, mediated by the coiled-coil region. Although PC2 Cterm has been extensively studied for its relationship with ADPKD and its importance in PC2 regulation, there are misunderstandings with respect to the definition of the domain topology within the PC2 Cterm and the functional role of each domain. Here, we review previous studies that connect the molecular properties of the domains of PC2 Cterm to distinct aspects of PC2 functions and regulation. PMID- 26857661 TI - A new theory of development: the generation of complexity in ontogenesis. AB - Today there is a very wide consensus on the idea that embryonic development is the result of a genetic programme and of epigenetic processes. Many models have been proposed in this theoretical framework to account for the various aspects of development, and virtually all of them have one thing in common: they do not acknowledge the presence of organic codes (codes between organic molecules) in ontogenesis. Here it is argued instead that embryonic development is a convergent increase in complexity that necessarily requires organic codes and organic memories, and a few examples of such codes are described. This is the code theory of development, a theory that was originally inspired by an algorithm that is capable of reconstructing structures from incomplete information, an algorithm that here is briefly summarized because it makes it intuitively appealing how a convergent increase in complexity can be achieved. The main thesis of the new theory is that the presence of organic codes in ontogenesis is not only a theoretical necessity but, first and foremost, an idea that can be tested and that has already been found to be in agreement with the evidence. PMID- 26857662 TI - Pragmatic information in biology and physics. AB - I will show how an objective definition of the concept of information and the consideration of recent results about information processing in the human brain help clarify some fundamental aspects of physics and biology. Rather than attempting to define information ab initio, I introduce the concept of interaction between material bodies as a primary concept. Two distinct categories can be identified: (i) interactions which can always be reduced to a superposition of physical interactions (forces) between elementary constituents; and (ii) interactions between complex bodies which cannot be expressed as a superposition of interactions between parts, and in which patterns and forms (in space and/or time) play the determining role. Pragmatic information is then defined as the link between a given pattern and the ensuing pattern-specific change. I will show that pragmatic information is a biological concept; it plays no active role in the purely physical domain-it only does so when a living organism intervenes. The consequences for physics (including foundations of quantum mechanics) and biology (including brain function) will be discussed. This will include speculations about three fundamental transitions, from the quantum to the classical domain, from natural inanimate to living systems, and from subhuman to human brain information-processing operations, introduced here in their direct connection with the concept of pragmatic information. PMID- 26857663 TI - What is information??. AB - Information is a precise concept that can be defined mathematically, but its relationship to what we call 'knowledge' is not always made clear. Furthermore, the concepts 'entropy' and 'information', while deeply related, are distinct and must be used with care, something that is not always achieved in the literature. In this elementary introduction, the concepts of entropy and information are laid out one by one, explained intuitively, but defined rigorously. I argue that a proper understanding of information in terms of prediction is key to a number of disciplines beyond engineering, such as physics and biology. PMID- 26857664 TI - Yury Borisovich Rumer and his 'biological papers' on the genetic code. AB - Yury Borisovich Rumer was one of the most important theoretical physicists of the former Soviet Union in the early 1930s. However, he also wrote a few 'biological papers' on the standard genetic code after he read Crick's and Nirenberg's pioneering papers on the topic. Rumer's articles on the 'Systematization of Codons in the Genetic Code' (Rumer 1966 Doklady Akademii nauk SSSR 167, 1393 1394); Rumer 1968 Doklady Akademii nauk SSSR 183, 225-226; Rumer 1969 Doklady Akademii nauk SSSR 187, 937-938, where he suggested the idea of partitioning codons depending on their redundancy-the first mention of symmetry in the genetic code-were published in Russian only. Due to their importance and their frequent citation, we here present translations of these articles into English in order to make them accessible to a broader community. PMID- 26857665 TI - Characterization of DNA methylation as a function of biological complexity via dinucleotide inter-distances. AB - We perform a statistical study of the distances between successive occurrences of a given dinucleotide in the DNA sequence for a number of organisms of different complexity. Our analysis highlights peculiar features of the CG dinucleotide distribution in mammalian DNA, pointing towards a connection with the role of such dinucleotide in DNA methylation. While the CG distributions of mammals exhibit exponential tails with comparable parameters, the picture for the other organisms studied (e.g. fish, insects, bacteria and viruses) is more heterogeneous, possibly because in these organisms DNA methylation has different functional roles. Our analysis suggests that the distribution of the distances between CG dinucleotides provides useful insights into characterizing and classifying organisms in terms of methylation functionalities. PMID- 26857666 TI - DNA as information. AB - This article reviews contributions to this theme issue covering the topic 'DNA as information' in relation to the structure of DNA, the measure of its information content, the role and meaning of information in biology and the origin of genetic coding as a transition from uninformed to meaningful computational processes in physical systems. PMID- 26857668 TI - Translation of 'Systematization of Codons in the Genetic Code [III]' by Yu. B. Rumer (1969). PMID- 26857667 TI - Translation of 'Systematization of Codons in the Genetic Code [II]' by Yu. B. Rumer (1968). PMID- 26857669 TI - Translation of 'Systematization of Codons in the Genetic Code [I]' by Yu. B. Rumer (1966). PMID- 26857670 TI - Directed self-assembly, genomic assembly complexity and the formation of biological structure, or, what are the genes for nacre? AB - Biology uses dynamical mechanisms of self-organization and self-assembly of materials, but it also choreographs and directs these processes. The difference between abiotic self-assembly and a biological process is rather like the difference between setting up and running an experiment to make a material remotely compared with doing it in one's own laboratory: with a remote experiment say on the International Space Station-everything must be set up beforehand to let the experiment run 'hands off', but in the laboratory one can intervene at any point in a 'hands-on' approach. It is clear that the latter process, of directed self-assembly, can allow much more complicated experiments and produce far more complex structures than self-assembly alone. This control over self assembly in biology is exercised at certain key waypoints along a trajectory and the process may be quantified in terms of the genomic assembly complexity of a biomaterial. PMID- 26857671 TI - Self-referring DNA and protein: a remark on physical and geometrical aspects. AB - All known life forms are based upon a hierarchy of interwoven feedback loops, operating over a cascade of space, time and energy scales. Among the most basic loops are those connecting DNA and proteins. For example, in genetic networks, DNA genes are expressed as proteins, which may bind near the same genes and thereby control their own expression. In this molecular type of self-reference, information is mapped from the DNA sequence to the protein and back to DNA. There is a variety of dynamic DNA-protein self-reference loops, and the purpose of this remark is to discuss certain geometrical and physical aspects related to the back and forth mapping between DNA and proteins. The mappings are examined as dimensional reductions and expansions between high- and low-dimensional manifolds in molecular spaces. The discussion raises basic questions regarding the nature of DNA and proteins as self-referring matter, which are examined in a simple toy model. PMID- 26857672 TI - What did Erwin mean? The physics of information from the materials genomics of aperiodic crystals and water to molecular information catalysts and life. AB - Erwin Schrodinger famously and presciently ascribed the vehicle transmitting the hereditary information underlying life to an 'aperiodic crystal'. We compare and contrast this, only later discovered to be stored in the linear biomolecule DNA, with the information-bearing, layered quasi-one-dimensional materials investigated by the emerging field of chaotic crystallography. Despite differences in functionality, the same information measures capture structure and novelty in both, suggesting an intimate coherence between the information character of biotic and abiotic matter-a broadly applicable physics of information. We review layered solids and consider three examples of how information- and computation-theoretic techniques are being applied to understand their structure. In particular, (i) we review recent efforts to apply new kinds of information measures to quantify disordered crystals; (ii) we discuss the structure of ice I in information-theoretic terms; and (iii) we recount recent investigations into the structure of tris(bicyclo[2.1.1]hexeno)benzene, showing how an information-theoretic analysis yields additional insight into its structure. We then illustrate a new Second Law of Thermodynamics that describes information processing in active low-dimensional materials, reviewing Maxwell's Demon and a new class of molecular devices that act as information catalysts. Lastly, we conclude by speculating on how these ideas from informational materials science may impact biology. PMID- 26857673 TI - The generation of meaningful information in molecular systems. AB - The physico-chemical processes occurring inside cells are under the computational control of genetic (DNA) and epigenetic (internal structural) programming. The origin and evolution of genetic information (nucleic acid sequences) is reasonably well understood, but scant attention has been paid to the origin and evolution of the molecular biological interpreters that give phenotypic meaning to the sequence information that is quite faithfully replicated during cellular reproduction. The near universality and age of the mapping from nucleotide triplets to amino acids embedded in the functionality of the protein synthetic machinery speaks to the early development of a system of coding which is still extant in every living organism. We take the origin of genetic coding as a paradigm of the emergence of computation in natural systems, focusing on the requirement that the molecular components of an interpreter be synthesized autocatalytically. Within this context, it is seen that interpreters of increasing complexity are generated by series of transitions through stepped dynamic instabilities (non-equilibrium phase transitions). The early phylogeny of the amino acyl-tRNA synthetase enzymes is discussed in such terms, leading to the conclusion that the observed optimality of the genetic code is a natural outcome of the processes of self-organization that produced it. PMID- 26857675 TI - The informational architecture of the cell. AB - We compare the informational architecture of biological and random networks to identify informational features that may distinguish biological networks from random. The study presented here focuses on the Boolean network model for regulation of the cell cycle of the fission yeast Schizosaccharomyces pombe. We compare calculated values of local and global information measures for the fission yeast cell cycle to the same measures as applied to two different classes of random networks: Erdos-Renyi and scale-free. We report patterns in local information processing and storage that do indeed distinguish biological from random, associated with control nodes that regulate the function of the fission yeast cell-cycle network. Conversely, we find that integrated information, which serves as a global measure of 'emergent' information processing, does not differ from random for the case presented. We discuss implications for our understanding of the informational architecture of the fission yeast cell-cycle network in particular, and more generally for illuminating any distinctive physics that may be operative in life. PMID- 26857674 TI - DNA as information: at the crossroads between biology, mathematics, physics and chemistry. AB - On the one hand, biology, chemistry and also physics tell us how the process of translating the genetic information into life could possibly work, but we are still very far from a complete understanding of this process. On the other hand, mathematics and statistics give us methods to describe such natural systems-or parts of them-within a theoretical framework. Also, they provide us with hints and predictions that can be tested at the experimental level. Furthermore, there are peculiar aspects of the management of genetic information that are intimately related to information theory and communication theory. This theme issue is aimed at fostering the discussion on the problem of genetic coding and information through the presentation of different innovative points of view. The aim of the editors is to stimulate discussions and scientific exchange that will lead to new research on why and how life can exist from the point of view of the coding and decoding of genetic information. The present introduction represents the point of view of the editors on the main aspects that could be the subject of future scientific debate. PMID- 26857676 TI - What is information? AB - Molecular biology is based on two great discoveries: the first is that genes carry hereditary information in the form of linear sequences of nucleotides; the second is that in protein synthesis a sequence of nucleotides is translated into a sequence of amino acids, a process that amounts to a transfer of information from genes to proteins. These discoveries have shown that the information of genes and proteins is the specific linear order of their sequences. This is a clear definition of information and there is no doubt that it reflects an experimental reality. What is not clear, however, is the ontological status of information, and the result is that today we have two conflicting paradigms in biology. One is the 'chemical paradigm', the idea that 'life is chemistry', or, more precisely, that 'life is an extremely complex form of chemistry'. The other is the 'information paradigm', the view that chemistry is not enough, that 'life is chemistry plus information'. This implies that there is an ontological difference between information and chemistry, a difference which is often expressed by saying that information-based processes like heredity and natural selection simply do not exist in the world of chemistry. Against this conclusion, the supporters of the chemical paradigm have argued that the concept of information is only a linguistic metaphor, a word that summarizes the result of countless underlying chemical reactions. The supporters of the information paradigm insist that information is a real and fundamental component of the living world, but have not been able to prove this point. As a result, the chemical view has not been abandoned and the two paradigms both coexist today. Here, it is shown that a solution to the ontological problem of information does exist. It comes from the idea that life is artefact-making, that genes and proteins are molecular artefacts manufactured by molecular machines and that artefacts necessarily require sequences and coding rules in addition to the quantities of physics and chemistry. More precisely, it is shown that the production of artefacts requires new observables that are referred to as nominable entities because they can be described only by naming their components in their natural order. From an ontological point of view, in conclusion, information is a nominable entity, a fundamental but not-computable observable. PMID- 26857677 TI - The problems of biological information. AB - The discovery of genetic encoding in the DNA molecule, and its mode of translation into protein structures, secured the modern view of biology as an information science. But it remains unclear what kind of information science it is. The all-too-ready analogy with computer programs stored on spools of magnetic tape has been hard to relinquish, even while the complexity of information storage and flow in the cell has become ever more apparent. To understand how life is sustained and evolves through encoding and processing of information, new ideas are now required, within which genetic encoding in DNA seems likely to provide only one part of a much broader and more profound puzzle. In particular, it seems likely that the emerging picture will need to take a more subtle view of causation, context and meaning in the orchestrated, hierarchical processes that make life possible. PMID- 26857679 TI - The non-power model of the genetic code: a paradigm for interpreting genomic information. AB - In this article, we present a mathematical framework based on redundant (non power) representations of integer numbers as a paradigm for the interpretation of genomic information. The core of the approach relies on modelling the degeneracy of the genetic code. The model allows one to explain many features and symmetries of the genetic code and to uncover hidden symmetries. Also, it provides us with new tools for the analysis of genomic sequences. We review briefly three main areas: (i) the Euplotid nuclear code, (ii) the vertebrate mitochondrial code, and (iii) the main coding/decoding strategies used in the three domains of life. In every case, we show how the non-power model is a natural unified framework for describing degeneracy and deriving sound biological hypotheses on protein coding. The approach is rooted on number theory and group theory; nevertheless, we have kept the technical level to a minimum by focusing on key concepts and on the biological implications. PMID- 26857678 TI - The meaning of biological information. AB - Biological information encoded in genomes is fundamentally different from and effectively orthogonal to Shannon entropy. The biologically relevant concept of information has to do with 'meaning', i.e. encoding various biological functions with various degree of evolutionary conservation. Apart from direct experimentation, the meaning, or biological information content, can be extracted and quantified from alignments of homologous nucleotide or amino acid sequences but generally not from a single sequence, using appropriately modified information theoretical formulae. For short, information encoded in genomes is defined vertically but not horizontally. Informally but substantially, biological information density seems to be equivalent to 'meaning' of genomic sequences that spans the entire range from sharply defined, universal meaning to effective meaninglessness. Large fractions of genomes, up to 90% in some plants, belong within the domain of fuzzy meaning. The sequences with fuzzy meaning can be recruited for various functions, with the meaning subsequently fixed, and also could perform generic functional roles that do not require sequence conservation. Biological meaning is continuously transferred between the genomes of selfish elements and hosts in the process of their coevolution. Thus, in order to adequately describe genome function and evolution, the concepts of information theory have to be adapted to incorporate the notion of meaning that is central to biology. PMID- 26857680 TI - n-Nucleotide circular codes in graph theory. AB - The circular code theory proposes that genes are constituted of two trinucleotide codes: the classical genetic code with 61 trinucleotides for coding the 20 amino acids (except the three stop codons {TAA,TAG,TGA}) and a circular code based on 20 trinucleotides for retrieving, maintaining and synchronizing the reading frame. It relies on two main results: the identification of a maximal C(3) self complementary trinucleotide circular code X in genes of bacteria, eukaryotes, plasmids and viruses (Michel 2015 J. Theor. Biol. 380, 156-177. (doi:10.1016/j.jtbi.2015.04.009); Arques & Michel 1996 J. Theor. Biol. 182, 45 58. (doi:10.1006/jtbi.1996.0142)) and the finding of X circular code motifs in tRNAs and rRNAs, in particular in the ribosome decoding centre (Michel 2012 Comput. Biol. Chem. 37, 24-37. (doi:10.1016/j.compbiolchem.2011.10.002); El Soufi & Michel 2014 Comput. Biol. Chem. 52, 9-17. (doi:10.1016/j.compbiolchem.2014.08.001)). The univerally conserved nucleotides A1492 and A1493 and the conserved nucleotide G530 are included in X circular code motifs. Recently, dinucleotide circular codes were also investigated (Michel & Pirillo 2013 ISRN Biomath. 2013, 538631. (doi:10.1155/2013/538631); Fimmel et al. 2015 J. Theor. Biol. 386, 159-165. (doi:10.1016/j.jtbi.2015.08.034)). As the genetic motifs of different lengths are ubiquitous in genes and genomes, we introduce a new approach based on graph theory to study in full generality n nucleotide circular codes X, i.e. of length 2 (dinucleotide), 3 (trinucleotide), 4 (tetranucleotide), etc. Indeed, we prove that an n-nucleotide code X is circular if and only if the corresponding graph [Formula: see text] is acyclic. Moreover, the maximal length of a path in [Formula: see text] corresponds to the window of nucleotides in a sequence for detecting the correct reading frame. Finally, the graph theory of tournaments is applied to the study of dinucleotide circular codes. It has full equivalence between the combinatorics theory (Michel & Pirillo 2013 ISRN Biomath. 2013, 538631. (doi:10.1155/2013/538631)) and the group theory (Fimmel et al. 2015 J. Theor. Biol. 386, 159-165. (doi:10.1016/j.jtbi.2015.08.034)) of dinucleotide circular codes while its mathematical approach is simpler. PMID- 26857681 TI - Bacteria differently regulate mRNA abundance to specifically respond to various stresses. AB - Environmental stress is detrimental to cell viability and requires an adequate reprogramming of cellular activities to maximize cell survival. We present a global analysis of the response of Escherichia coli to acute heat and osmotic stress. We combine deep sequencing of total mRNA and ribosome-protected fragments to provide a genome-wide map of the stress response at transcriptional and translational levels. For each type of stress, we observe a unique subset of genes that shape the stress-specific response. Upon temperature upshift, mRNAs with reduced folding stability up- and downstream of the start codon, and thus with more accessible initiation regions, are translationally favoured. Conversely, osmotic upshift causes a global reduction of highly translated transcripts with high copy numbers, allowing reallocation of translation resources to not degraded and newly synthesized mRNAs. PMID- 26857684 TI - Evaluation of Left and Right Atrial Function in Patients with Coronary Slow-Flow Phenomenon Using Two-Dimensional Speckle Tracking Echocardiography. AB - BACKGROUND: Coronary slow-flow phenomenon (CSFP) is an angiographic diagnosis characterized by delayed coronary opacification in the absence of obstructive coronary artery disease. Currently, several investigators are focusing on ventricular function assessment in patients with CSFP; however, there is a paucity of data on their atrial function. This study was performed to evaluate left atrial (LA) and right atrial (RA) function in patients with CSFP. MATERIALS AND METHODS: Eighty-two patients with CSFP and 55 controls without CSFP were enrolled in the study. Diagnosis of CSFP was made by thrombolysis in myocardial infarction frame count (TFC). The LA and RA global longitudinal strain and strain rate during systole (Ss, SRs), during early diastole (Se, SRe), and during late diastole (Sa, SRa) were measured using two-dimensional speckle tracking echocardiography. RESULTS: In the CSFP group, LA Se and SRe decreased, while LA Sa and SRa increased, compared with the control group. RA Se and SRe were lower in patients with CSFP than in the controls. CONCLUSIONS: LA conduit function decreased in patients with CSFP, while contractile function increased. RA conduit function also decreased in patients with CSFP. PMID- 26857683 TI - Impact on quality of life of a nursing intervention programme for patients with chronic non-cancer pain: an open, randomized controlled parallel study protocol. AB - AIM: To determine the effect of a nurse-led intervention programme for patients with chronic non-cancer pain. BACKGROUND: Chronic non-cancer pain is a widespread health problem and one that is insufficiently controlled. Nurses can play a vital role in pain management, using best practices in the assessment and management of pain under a holistic approach where the patient plays a proactive role in addressing the disease process. Improving the quality of life, reducing disability, achieving acceptance of health status, coping and breaking the vicious circle of pain should be the prime objectives of our care management programme. DESIGN: Open randomized parallel controlled study. METHODS: The experimental group will undertake one single initial session, followed by six group sessions led by nurses, aimed at empowering patients for the self management of pain. Healthy behaviours will be encouraged, such as sleep and postural hygiene, promotion of physical activity and healthy eating. Educational interventions on self-esteem, pain-awareness, communication and relaxing techniques will be carried out. As primary end points, quality of life, perceived level of pain, anxiety and depression will be evaluated. Secondary end points will be coping and satisfaction. Follow-up will be performed at 12 and 24 weeks. The study was approved by the Ethics and Research Committee Costa del Sol. DISCUSSION: If significant effects were detected, impact on quality of life through a nurse-led programme would offer a complementary service to existing pain clinics for a group of patients with frequent unmet needs. PMID- 26857682 TI - Candidate Surrogate End Points for ESRD after AKI. AB - AKI, a frequently transient condition, is not accepted by the US Food and Drug Association as an end point for drug registration trials. We assessed whether an intermediate-term change in eGFR after AKI has a sufficiently strong relationship with subsequent ESRD to serve as an alternative end point in trials of AKI prevention and/or treatment. Among 161,185 United States veterans undergoing major surgery between 2004 and 2011, we characterized in-hospital AKI by Kidney Disease Improving Global Outcomes creatinine criteria and decline in eGFR from prehospitalization to postdischarge time points and quantified associations of these values with ESRD and mortality over a median of 3.8 years. An eGFR decline of >=30% at 30, 60, and 90 days after discharge occurred in 3.1%, 2.5%, and 2.6%, of survivors without AKI and 15.9%, 12.2%, and 11.7%, of survivors with AKI. For patients with in-hospital AKI compared with those with no AKI and stable eGFR, a 30% decline in eGFR at 30, 60, and 90 days after discharge demonstrated adjusted hazard ratios (95% confidence intervals) of ESRD of 5.60 (4.06 to 7.71), 6.42 (4.76 to 8.65), and 7.27 (5.14 to 10.27), with corresponding estimates for 40% decline in eGFR of 6.98 (5.21 to 9.35), 8.03 (6.11 to 10.56), and 10.95 (8.10 to 14.82). Risks for mortality were smaller but consistent in direction. A 30%-40% decline in eGFR after AKI could be a surrogate end point for ESRD in trials of AKI prevention and/or treatment, but additional trial evidence is needed. PMID- 26857685 TI - PPAR Agonists: I. Role of Receptor Subunits in Alcohol Consumption in Male and Female Mice. AB - BACKGROUND: Several peroxisome proliferator-activated receptor (PPAR) agonists reduce voluntary alcohol consumption in rodent models, and evidence suggests that PPARalpha and gamma subunits play an important role in this effect. To define the subunit dependence of this action, we tested selective PPARalpha and alpha/gamma agonists and antagonists in addition to null mutant mice lacking PPARalpha. METHODS: The effects of fenofibrate (PPARalpha agonist) and tesaglitazar (PPARalpha/gamma agonist) on continuous and intermittent 2-bottle choice drinking tests were examined in male and female wild-type mice and in male mice lacking PPARalpha. We compared the ability of MK886 (PPARalpha antagonist) and GW9662 (PPARgamma antagonist) to inhibit the effects of fenofibrate and tesaglitazar in wild-type mice. The estrogen receptor antagonist, tamoxifen, can inhibit PPARgamma-dependent transcription and was also studied in male and female mice. RESULTS: Fenofibrate and tesaglitazar reduced ethanol (EtOH) consumption and preference in wild-type mice, but these effects were not observed in mice lacking PPARalpha. MK886 inhibited the action of fenofibrate, but not tesaglitazer, while GW9662 did not inhibit either agonist. The PPAR agonists were more effective in male mice compared to females, and drinking in the continuous 2-bottle choice test was more sensitive to fenofibrate and tesaglitazar compared to drinking in the intermittent access test. Tamoxifen also reduced EtOH consumption in male mice and this action was inhibited by GW9662, but not MK886, suggesting that it acts by activation of PPARgamma. CONCLUSIONS: Our study using selective PPAR agonists, antagonists, and null mutant mice indicates a key role for PPARalpha in mediating reduced EtOH consumption by fenofibrate and tesaglitazar. PMID- 26857686 TI - Identification of imine reductase-specific sequence motifs. AB - Chiral amines are valuable building blocks for the production of a variety of pharmaceuticals, agrochemicals and other specialty chemicals. Only recently, imine reductases (IREDs) were discovered which catalyze the stereoselective reduction of imines to chiral amines. Although several IREDs were biochemically characterized in the last few years, knowledge of the reaction mechanism and the molecular basis of substrate specificity and stereoselectivity is limited. To gain further insights into the sequence-function relationships, the Imine Reductase Engineering Database (www.IRED.BioCatNet.de) was established and a systematic analysis of 530 putative IREDs was performed. A standard numbering scheme based on R-IRED-Sk was introduced to facilitate the identification and communication of structurally equivalent positions in different proteins. A conservation analysis revealed a highly conserved cofactor binding region and a predominantly hydrophobic substrate binding cleft. Two IRED-specific motifs were identified, the cofactor binding motif GLGxMGx(5 )[ATS]x(4) Gx(4) [VIL]WNR[TS]x(2) [KR] and the active site motif Gx[DE]x[GDA]x[APS]x(3){K}x[ASL]x[LMVIAG]. Our results indicate a preference toward NADPH for all IREDs and explain why, despite their sequence similarity to beta-hydroxyacid dehydrogenases (beta-HADs), no conversion of beta-hydroxyacids has been observed. Superfamily-specific conservations were investigated to explore the molecular basis of their stereopreference. Based on our analysis and previous experimental results on IRED mutants, an exclusive role of standard position 187 for stereoselectivity is excluded. Alternatively, two standard positions 139 and 194 were identified which are superfamily-specifically conserved and differ in R- and S-selective enzymes. PMID- 26857687 TI - Peritoneal inflammation and fibrosis in C-reactive protein transgenic mice undergoing peritoneal dialysis solution treatment. AB - AIM: C-reactive protein (CRP) is a mediator of systemic inflammation. Peritoneal dialysis (PD) is known to cause peritoneal inflammation and fibrosis. We compare the degree of peritoneal inflammation and fibrosis in wild-type (WT) and CRP transgenic (Tg) mice after PD treatment. METHODS: WT (n = 7) and CRP-Tg (n = 10) C57BL/6 J mice (all male, 10-12 weeks old) were injected intra-peritoneally with 4.25% dextrose PD solution (3 mL/mouse) daily for 28 days, followed by a 2-h peritoneal equilibration test (PET). The mice were then killed. Parietal peritoneal and omental tissues were collected for the assessment of inflammation and fibrosis. RESULTS: After 28 days of PD treatment, CRP-Tg mice had higher dialysate-to-plasma (D/P) creatinine ratio than that of WT mice. Parietal peritoneum of the CRP-Tg mice was more cellular and thicker than that of the WT mice. CRP-Tg mice also had higher connective tissue growth factor (CTGF), intercellular adhesion molecule 1 (ICAM1) and tumor necrosis factor alpha (TNFalpha) RNA expressions as well as immunohistochemical staining in the parietal peritoneum than that of the WT mice. CONCLUSIONS: CRP-Tg mice have significantly more inflammation and fibrosis than WT mice after PD treatment. Our results suggest that CRP play a role in inflammation and fibrosis induced by PD. The implication of our results to human PD therapy needs further investigations. PMID- 26857688 TI - A multicenter phase II study of sepantronium bromide (YM155) plus rituximab in patients with relapsed aggressive B-cell Non-Hodgkin lymphoma. AB - This phase II study evaluated YM155, a novel small-molecule survivin suppressant, in combination with rituximab in patients with relapsed aggressive B-cell non Hodgkin lymphoma (NHL) who failed or were not candidates for autologous stem cell transplant (ASCT). During 14-day cycles, 41 patients received YM155 (5mg/m(2)/d) by continuous intravenous (IV) infusion for 168 hours (day 1-7), and rituximab (375mg/m(2)) IV on days 1 and 8 during cycles 1-4 and repeated for 4 cycles every 10 cycles. Forty patients (97.6%) had prior rituximab and 15 patients (36.6%) prior ASCT. Most frequent grade 3-4 adverse events were neutropenia (19.5%) and thrombocytopenia (12.2%). In the per-protocol set (n = 34), objective response rate was 50% and median progression-free survival 17.9 months. Median overall survival was not reached at study termination (median follow-up, 23 months). YM155 in combination with rituximab was tolerable with encouraging antitumor activity and durable responses in relapsed aggressive B-cell NHL patients. PMID- 26857689 TI - Evaluation of topical antifungal products in an in vitro onychomycosis model. AB - Many topical commercial products are currently available for the treatment of onychomycosis. However, limited data are available concerning their antifungal activity. Using an in vitro onychomycosis model, the daily application of seven nail formulations was compared to the antifungal reference drug amorolfine (Loceryl((r)) ) and evaluated for inhibitory activity against Trichophyton mentagrophytes using an agar diffusion test. Of all commercial nail formulations, only Excilor((r)) and Nailner((r)) demonstrated inhibitory activity, which was much lower compared to the daily application of Loceryl((r)) . However, Excilor((r)) showed similar efficacy compared to the conventional weekly application of Loceryl((r)) . These results suggest a role for organic acids in the antifungal effect of Excilor((r)) (acetic acid, ethyl lactate) and Nailner((r)) (lactic acid, citric acid, ethyl lactate) as all tested formulations without organic acids were inactive. PMID- 26857691 TI - Using subject-specific three-dimensional (3D) anthropometry data in digital human modelling: case study in hand motion simulation. AB - Digital human modelling enables ergonomists and designers to consider ergonomic concerns and design alternatives in a timely and cost-efficient manner in the early stages of design. However, the reliability of the simulation could be limited due to the percentile-based approach used in constructing the digital human model. To enhance the accuracy of the size and shape of the models, we proposed a framework to generate digital human models using three-dimensional (3D) anthropometric data. The 3D scan data from specific subjects' hands were segmented based on the estimated centres of rotation. The segments were then driven in forward kinematics to perform several functional postures. The constructed hand models were then verified, thereby validating the feasibility of the framework. The proposed framework helps generate accurate subject-specific digital human models, which can be utilised to guide product design and workspace arrangement. Practitioner Summary: Subject-specific digital human models can be constructed under the proposed framework based on three-dimensional (3D) anthropometry. This approach enables more reliable digital human simulation to guide product design and workspace arrangement. PMID- 26857692 TI - Recognition of subtle and universal facial expressions in a community-based sample of adults classified with intellectual disability. AB - BACKGROUND: Across the USA and UK, schemes now exist to aid the successful integration of adults with mild to moderate intellectual disabilities into general society. One factor that may prove important to the success of such schemes is social competence. Here, understanding the facial expressions of others is critical, as emotion recognition is a prerequisite to empathetic responding and an essential factor in social functioning. Yet research in this area is lacking, especially in community-based samples. METHOD: We investigated the performance of 13 adults with mild to moderate intellectual disability (ID), relative to 13 age-matched controls, on three tasks of emotion recognition (emotion categorisation; recognition of valence; and recognition of arousal), using a number of 'basic' (angry and happy) and more 'subtle' (compassionate and critical) emotional expressions, as well as the posers face in a default relaxed (i.e. 'neutral') state. Importantly, the sample was drawn from a community-based initiative and was therefore representative of populations' government schemes target. RESULTS: Across emotion recognition tasks, the ID adults, as compared with controls, were significantly impaired when labelling the emotions displayed by the poser as well as recognising the associated 'feelings' conveyed by these faces. This was especially true for the neutral, compassionate and angry facial expressions. For example, ID adults demonstrated deficits in categorising neutral and subtle emotional expressions, as well as assessing the valence of such facial expressions. In addition, ID adults also struggled to assess arousal levels; especially those associated with compassionate and angry faces. CONCLUSION: Given both basic and subtle emotions are conveyed in a range of daily situations, errors in interpreting such facial expressions and, relatedly, understanding what potential behaviours such expressions signify could contribute to the social difficulties ID adults face. This is important because current initiatives such as 'personalisation' do not appear to have schemes supporting training in this area, and understanding the facial expressions of others is, after all, one of our most important non-verbal social communication tools. PMID- 26857693 TI - Symposium Summary: "Breathe In, Breathe Out, Its Easy: What You Need to Know About Developing Inhaled Drugs". AB - Developing inhaled drugs requires knowledge of lung anatomy, cell biology, respiratory physiology, particle physics, and some plumbing. Although dose makes the poison, in the context of an inhaled drug, the "dose" is not easily defined. This lack of clarity around dose poses issues and challenges in the design of inhalation toxicology programs. To better understand dose, the influence of ventilation is discussed as are the perturbations in pulmonary function observed with inhalation exposure that can affect dose. Methods for determining inhaled drug deposition to arrive at an estimate of lung dose are examined. Equally important to understanding dose are the techniques used to deliver aerosols to animals. With a better understanding of dose and inhalation exposure, species specific histopathologic lesions, both common background and toxicologically significant lesions, are reviewed. Finally, insight into how regulators synthesize and evaluate these complex findings to assess clinical safety risks is presented. PMID- 26857694 TI - Heterogeneity of chromatoid bodies in adult pluripotent stem cells of planarian Dugesia japonica. AB - The robust regenerative ability of planarians is known to be dependent on adult pluripotent stem cells called neoblasts. One of the morphological features of neoblasts is cytoplasmic ribonucleoprotein granules (chromatoid bodies: CBs), which resemble germ granules present in germline cells in other animals. Previously, we showed by immuno-electron microscopic analysis that DjCBC-1, a planarian Me31B/Dhh1/DDX6 homologue, which is a component of ribonucleoprotein granules, was localized in CBs in the planarian Dugesia japonica. Also, recently it was reported using another planarian species that Y12 antibody recognizing symmetrical dimethylarginine (sDMA) specifically binds to CBs in which histone mRNA is co-localized. Here, we showed by double immunostaining and RNA interference (RNAi) that DjCBC-1-containing CBs and Y12-immunoreactive CBs are distinct structures, suggesting that CBs are composed of heterogeneous populations. We also found that the Y12-immunoreactive CBs specifically contained a cytoplasmic type of planarian PIWI protein (DjPiwiC). We revealed by RNAi experiments that Y12-immunoreactive CBs may have anti-transposable element activity involving the DjPiwiC protein in the neoblasts. PMID- 26857695 TI - Admissions to hospital due to fracture in England in patients with prostate cancer treated with androgen-deprivation therapy - do we have to worry about the hormones? AB - OBJECTIVE: To investigate the association between androgen-deprivation therapy (ADT) and fracture risk in men with prostate cancer in England. PATIENTS AND METHODS: Using the Hospital Episodes Statistics database, which contains all the information about National Health Service (NHS) and NHS-funded hospital admissions in England, for the years 2004-2008, 8 902 patients were found to have had prostate cancer and an admission to hospital with a fracture. Of these patients, 3 372 (37.8%) were identified as being treated with ADT, whilst 5 530 (62.2%) were not. There was a total of 228 852 admissions in the background population. RESULTS: The risk of a fracture requiring hospitalisation increased from 1.12 to 1.41 per 100 person-years in a man with prostate cancer treated with ADT compared with those without ADT, an absolute increase of only 0.29 per 100 person-years. When compared with the background population, there was an increase from 0.58 to 1.41 per 100 person-years, a relative rate ratio increase of 2.4 (P < 0.01) with an absolute increase of 0.83 per 100 person-years. CONCLUSION: In England there was a small but statistically significant increased risk of fracture in men who had been treated with ADT. Men with prostate cancer, with or without ADT, were at an increased risk of fracture compared with the background population. We therefore suggest that if bone health is to be taken seriously in men with prostate cancer that all these men should be risk assessed (FRAX((r)) or Qfracture((r)) tools, as National Institute for Health and Care Excellence advised), as all men with prostate cancer have an increased risk of fracture, with those on ADT having slightly higher risk. PMID- 26857696 TI - Formation of whey protein-polyphenol meso-structures as a natural means of creating functional particles. AB - Whey proteins provide structure and nutritional properties in food, while berry juices are thought to have biological activity that can impart anti-inflammatory health effects. In combination, the two could be an excellent source of necessary and supplemental nutrients as well as expand the functionality of whey proteins in food structures. The objectives of this investigation were to (1) develop an approach for particle formation between whey protein and cranberry, blackcurrant, or muscadine grape juices, (2) determine resulting particle composition and physical characteristics, and (3) evaluate properties related to food structure stability and maintenance of phytochemical bioactivity. Particles were formed by combining 20% w/w whey protein with juice containing 50, 250, or 500 MUg g(-1) total phenolics, adjusting pH to 4.5, and centrifuging to collect aggregated particles. Particles had an approximate molar ratio of 9-50 proteins per polyphenol, and the ratio increased with increasing phenolic content of the juice used to create the particles. Particle size ranged from 1-100 MUm at pH 4.5, compared to 10 MUm particles that formed when whey protein isolate alone was precipitated at pH 4.5. Polyphenols and other juice components, such as acids and sugars appeared to be involved in particle formation. Particles improved foam stability, and the anti-inflammatory properties of entrapped polyphenols were maintained in the particles. Highly functional protein-polyphenol particles can be designed to stabilize food structures and simultaneously deliver polyphenols associated with health benefits. PMID- 26857697 TI - A systematic review of lactoferrin use in dermatology. AB - Lactoferrin is a glycoprotein widely present in mammalian secretions and possesses documented protective effects, including antimicrobial and anti inflammatory properties. While its therapeutic use is being investigated for a myriad of diseases, there is increasing interest in its application for skin disease. Our objective was to systematically review the clinical evidence for the use and efficacy of lactoferrin for the treatment of dermatological conditions. Pubmed and Embase databases were searched for clinical studies evaluating lactoferrin for dermatological conditions. A total of six studies were reviewed. Of the current clinical trials, there is encouraging evidence to suggest that lactoferrin may be beneficial in acne, psoriasis, and diabetic ulcerations. Although the current evidence is promising, further research is necessary to establish lactoferrin as complementary therapy in the clinical setting. PMID- 26857698 TI - Genome-wide DNA methylation analysis in multiple tissues in primary Sjogren's syndrome reveals regulatory effects at interferon-induced genes. AB - OBJECTIVES: Increasing evidence suggests an epigenetic contribution to the pathogenesis of autoimmune diseases, including primary Sjogren's Syndrome (pSS). The aim of this study was to investigate the role of DNA methylation in pSS by analysing multiple tissues from patients and controls. METHODS: Genome-wide DNA methylation profiles were generated using HumanMethylation450K BeadChips for whole blood, CD19+ B cells and minor salivary gland biopsies. Gene expression was analysed in CD19+ B cells by RNA-sequencing. Analysis of genetic regulatory effects on DNA methylation at known pSS risk loci was performed. RESULTS: We identified prominent hypomethylation of interferon (IFN)-regulated genes in whole blood and CD19+ B cells, including at the genes MX1, IFI44L and PARP9, replicating previous reports in pSS, as well as identifying a large number of novel associations. Enrichment for genomic overlap with histone marks for enhancer and promoter regions was observed. We showed for the first time that hypomethylation of IFN-regulated genes in pSS B cells was associated with their increased expression. In minor salivary gland biopsies we observed hypomethylation of the IFN-induced gene OAS2. Pathway and disease analysis resulted in enrichment of antigen presentation, IFN signalling and lymphoproliferative disorders. Evidence for genetic control of methylation levels at known pSS risk loci was observed. CONCLUSIONS: Our study highlights the role of epigenetic regulation of IFN-induced genes in pSS where replication is needed for novel findings. The association with altered gene expression suggests a functional mechanism for differentially methylated CpG sites in pSS aetiology. PMID- 26857700 TI - MDMA-induced angioedema treated with icatibant. PMID- 26857699 TI - Can rheumatoid arthritis (RA) registries provide contextual safety data for modern RA clinical trials? The case for mortality and cardiovascular disease. AB - BACKGROUND: We implemented a novel method for providing contextual adverse event rates for a randomised controlled trial (RCT) programme through coordinated analyses of five RA registries, focusing here on cardiovascular disease (CVD) and mortality. METHODS: Each participating registry (Consortium of Rheumatology Researchers of North America (CORRONA) (USA), Swedish Rheumatology Quality of Care Register (SRR) (Sweden), Norfolk Arthritis Register (NOAR) (UK), CORRONA International (East Europe, Latin America, India) and Institute of Rheumatology, Rheumatoid Arthritis (IORRA) (Japan)) defined a main cohort from January 2000 onwards. To address comparability and potential bias, we harmonised event definitions and defined several subcohorts for sensitivity analyses based on disease activity, treatment, calendar time, duration of follow-up and RCT exclusions. Rates were standardised for age, sex and, in one sensitivity analysis, also HAQ. RESULTS: The combined registry cohorts included 57 251 patients with RA (234 089 person-years)-24.5% men, mean (SD) baseline age 58.2 (13.8) and RA duration 8.2 (11.7) years. Standardised registry mortality rates (per 100 person-years) varied from 0.42 (CORRONA) to 0.80 (NOAR), with 0.60 for RCT patients. Myocardial infarction and major adverse cardiovascular events (MACE) rates ranged from 0.09 and 0.31 (IORRA) to 0.39 and 0.77 (SRR), with RCT rates intermediate (0.18 and 0.42), respectively. Additional subcohort analyses showed small and mostly consistent changes across registries, retaining reasonable consistency in rates across the Western registries. Additional standardisation for HAQ returned higher mortality and MACE registry rates. CONCLUSIONS: This coordinated approach to contextualising RA RCT safety data demonstrated reasonable differences and consistency in rates for mortality and CVD across registries, and comparable RCT rates, and may serve as a model method to supplement clinical trial analyses for drug development programmes. PMID- 26857701 TI - Predictors of dentists' behaviours in delivering prevention in primary dental care in England: using the theory of planned behaviour. AB - BACKGROUND: To explore the factors predicting preventive behaviours among NHS dentists in Camden, Islington and Haringey in London, using constructs from the Theory of Planned Behaviour. METHODS: A cross-sectional survey of NHS dentists working in North Central London was conducted. A self-completed questionnaire based on the theoretical framework of the Theory of Planned Behaviour was developed. It assessed dentists' attitudes, current preventive activities, subjective norms and perceived behavioural control in delivering preventive care. In model 1, logistic regression was conducted to assess the relationship between a range of preventive behaviours (diet, smoking and alcohol) and the three TPB constructs attitude, subjective norms and perceived behavioural control. Model 2 was adjusted for intention. RESULTS: Overall, 164 questionnaires were returned (response rate: 55.0%). Dentists' attitudes were important predictors of preventive behaviours among a sample of dentists in relation to asking and providing diet, alcohol and tobacco advice. A dentist was 3.73 times (95 % CI: 1.70, 8.18) more likely ask about a patient's diet, if they had a positive attitude towards prevention, when adjusted for age, sex and intention. A similar pattern emerged for alcohol advice (OR 2.35, 95 % CI 1.12, 4.96). Dentists who had a positive attitude were also 2.59 times more likely to provide smoking cessation advice. CONCLUSIONS: The findings of this study have demonstrated that dentists' attitudes are important predictors of preventive behaviours in relation to delivery of diet, smoking and alcohol advice. PMID- 26857702 TI - Optimal regimen of trastuzumab in combination with oxaliplatin/ capecitabine in first-line treatment of HER2-positive advanced gastric cancer (CGOG1001): a multicenter, phase II trial. AB - BACKGROUND: The ToGA study showed that trastuzumab plus chemotherapy prolonged median survival in patients with human epidermal growth factor receptor 2 (HER2) positive advanced gastric cancer. Among chemotherapy options, oxaliplatin might be as effective as cisplatin but has shown to be more tolerable. To further improve treatment options for patients with advanced gastric cancer, we initiated a study to evaluate the efficacy and safety of trastuzumab plus oxaliplatin/capecitabine in patients with HER2-positive advanced gastric cancer. METHODS: CGOG1001 was an open-label, multicenter, prospective phase II study. Patients with chemotherapy-naive HER2-positive advanced gastric cancer were eligible. Trastuzumab was administered at a loading dose of 8 mg/kg followed by 6 mg/kg infusion every 3 weeks (q3w). Oxaliplatin was administrated as a 130 mg/m(2) infusion, q3w, for up to 6 cycles. Capecitabine 1000 mg/m(2) was given orally twice daily on days 1-14 followed by a 7-day rest interval. Trastuzumab and capecitabine were continued until disease progression or intolerable toxicity. The primary endpoint was objective response rate. Simon two-stage design (H0 = 40%, H1 = 60%, alpha = 0.05, beta = 0.2) by Response Evaluation Criteria In Solid Tumors 1.0 was applied. RESULTS: Fifty-one patients were enrolled. Confirmed response was recorded in 46 patients. One patient achieved complete response and 33 patients achieved partial response (response rate 34/51 [66.7%] in the intent-to-treat population). Median follow-up time was 28.6 months, with a median progression-free survival of 9.2 months (95% confidence interval [CI]: 6.5-11.6) and a median overall survival (OS) of 19.5 months (95% CI: 15.5-26.0). Patients with a HER2/CEP17 ratio of greater than five achieved improved OS (20.9 vs 19.5 months, p = 0.001). The most common adverse events of grade 3 or above were thrombocytopenia (21.6%), neutropenia (13.7%), anemia (5.9 %) and leucopenia (3.9%). CONCLUSION: The addition of trastuzumab to oxaliplatin/capecitabine was well tolerated and the results demonstrated encouraging efficacy. TRIAL REGISTRATION: ClinicalTrials.gov NCT01364493. PMID- 26857703 TI - Endoscopic biopsy of islet transplants in the gastric submucosal space provides evidence of islet graft rejection in diabetic pigs. AB - Transplantation of islets into the gastric submucosal space (GSMS) has several advantages (e.g., avoidance of the instant blood-mediated inflammatory response [IBMIR], ability to biopsy). The aim of this study was to determine whether endoscopic biopsy of islet allografts transplanted into the GSMS in diabetic pigs can provide histopathological and immunohistochemical information that correlates with the clinical course (e.g.,, blood glucose level, insulin requirement). Islet allografts (Group1: 10,000 kIEq /kg [n = 4]; Group2: 15,000 kIEq /kg [n = 2]) were transplanted into the GSMS of diabetic pigs under immunosuppression. In Group2, the anti-oxidant, BMX-001 was applied during preservation, isolation, and culture of the islets, and at the time of transplantation. Endoscopic biopsies of the islet grafts were obtained one or 2 weeks after transplantation, and histopathological features were compared with the clinical course (e.g., blood glucose, insulin requirement). In Group1, in the absence of anti-oxidant therapy, most of the islets became fragmented, and there was no reduction in exogenous insulin requirement. In Group2, with an increased number of transplanted islets in the presence of BMX-001, more healthy insulin-positive islet masses were obtained at biopsy and necropsy (4 weeks), and these correlated with reductions in both blood glucose level and insulin requirement. In all cases, inflammatory cell infiltrates were present. After islet transplantation into the GSMS, endoscopic biopsy can provide information on graft rejection, which would be an immense advantage in clinical islet transplantation. PMID- 26857704 TI - First clinical study of a novel complete metal-free ceramic total knee replacement system. AB - BACKGROUND: The aim of the study was to evaluate the safety and efficacy of a novel metal-free ceramic total knee replacement system. METHODS: Thirty-eight primary total knee arthroplasties (TKAs) were performed on 34 patients using the metal-free BPK-S ceramic total knee replacement system with both the femoral and tibial components of an alumina/zirconia ceramic composite. The clinical outcome was evaluated pre- and postoperatively at 3 (n = 32 TKA) and 12 months (n = 32 TKA) using the Knee Society Score (KSS), the Oxford Knee Score and the EQ-5D. Safety analysis was performed by radiological examination and assessment of adverse events. RESULTS: Postoperatively, the KSS, Oxford Knee Score and EQ-5D improved significantly at 3 and 12 months (p < 0.001). Non-progressive partial radiolucent lines were observed in six cases, but there was no osteolysis and no implant loosening. Induction or exacerbation of allergies did not occur during the follow-up. CONCLUSIONS: The metal-free BPK-S ceramic total knee replacement system proved to be a safe and clinically efficient alternative to metal implants in this short-term follow-up study. PMID- 26857705 TI - The effect of early postnatal discharge from hospital for women and infants: a systematic review protocol. AB - BACKGROUND: The length of postnatal hospital stay has declined over the last 40 years. There is little evidence to support a policy of early discharge following birth, and there is some concern about whether early discharge of mothers and babies is safe. The Cochrane review on the effects of early discharge from hospital only included randomised controlled trials (RCTs) which are problematic in this area, and a systematic review including other study designs is required. The aim of this broader systematic review is to determine possible effects of a policy of early postnatal discharge on important maternal and infant health related outcomes. METHODS/DESIGN: A systematic search of published literature will be conducted for randomised controlled trials, non-randomised controlled trials (NRCTs), controlled before-after studies (CBA), and interrupted time series studies (ITS) that report on the effect of a policy of early postnatal discharge from hospital. Databases including Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and Science Citation Index will be searched for relevant material. Reference lists of articles will also be searched in addition to searches to identify grey literature. Screening of identified articles and data extraction will be conducted in duplicate and independently. Methodological quality of the included studies will be assessed using the Effective Practice and Organisation of Care (EPOC) criteria for risk of bias tool. Discrepancies will be resolved by consensus or by consulting a third author. Meta-analysis using a random effects model will be used to combine data. Where significant heterogeneity is present, data will be combined in a narrative synthesis. The findings will be reported according to the preferred reporting items for systematic reviews (PRISMA) statement. DISCUSSION: Information on the effects of early postnatal discharge from hospital will be important for policy makers and clinicians providing maternity care. This review will also identify any gaps in the current literature on this topic and provide direction for future research in this area of study. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015020545. PMID- 26857706 TI - Assessment of chiropractic treatment for active duty, U.S. military personnel with low back pain: study protocol for a randomized controlled trial. AB - BACKGROUND: Low back pain is highly prevalent and one of the most common causes of disability in U.S. armed forces personnel. Currently, no single therapeutic method has been established as a gold standard treatment for this increasingly prevalent condition. One commonly used treatment, which has demonstrated consistent positive outcomes in terms of pain and function within a civilian population is spinal manipulative therapy provided by doctors of chiropractic. Chiropractic care, delivered within a multidisciplinary framework in military healthcare settings, has the potential to help improve clinical outcomes for military personnel with low back pain. However, its effectiveness in a military setting has not been well established. The primary objective of this study is to evaluate changes in pain and disability in active duty service members with low back pain who are allocated to receive usual medical care plus chiropractic care versus treatment with usual medical care alone. METHODS/DESIGN: This pragmatic comparative effectiveness trial will enroll 750 active duty service members with low back pain at three military treatment facilities within the United States (250 from each site) who will be allocated to receive usual medical care plus chiropractic care or usual medical care alone for 6 weeks. Primary outcomes will include the numerical rating scale for pain intensity and the Roland-Morris Disability Questionnaire at week 6. Patient reported outcomes of pain, disability, bothersomeness, and back pain function will be collected at 2, 4, 6, and 12 weeks from allocation. DISCUSSION: Because low back pain is one of the leading causes of disability among U.S. military personnel, it is important to find pragmatic and conservative treatments that will treat low back pain and preserve low back function so that military readiness is maintained. Thus, it is important to evaluate the effects of the addition of chiropractic care to usual medical care on low back pain and disability. TRIAL REGISTRATION: The trial discussed in this article was registered in ClinicalTrials.gov with the NCT01692275 Date of registration: 6 September 2012. PMID- 26857708 TI - Current Trends in the Oncologic and Surgical Managements of Breast Cancer in Women with Implants: Incidence, Diagnosis, and Treatment. AB - Breast augmentation is the most common cosmetic surgery in the United States, and thousands of augmented patients develop breast cancer each year. The possible effects of implants on cancer incidence, diagnosis, and treatment usually generate a disarming confusion. The present paper represents an update of the more recent oncologic and surgical strategies, aiming to support plastic and general surgeons in such challenging aspects. Several aspects of breast cancer management in augmented women are investigated, including (1) risk estimation and cancer characteristics, stage at diagnosis, and prognosis; (2) cancer diagnosis with clinical examination, mammography, ultrasound, and magnetic resonance imaging; (3) cancer treatment including breast conservation, intraoperative radiotherapy, sentinel node biopsy and mastectomy, and reconstruction. A brief resume of recommendations and conclusions is suggested, elucidating correct trends in the oncologic management of augmented patients and refusing well established misconceptions: (1) breast augmentation does not increase the risk of breast cancer incidence, and it does not influence the prognosis; (2) possible risks exist in cancer detection due to technical difficulties; (3) sentinel lymph node detection is feasible; (4) intraoperative radiotherapy represents a good chance for conserving treatment; (5) immediate reconstruction with submuscular subfascial implants is the most common procedure after mastectomy, and biological substitutes could support this procedure. Breast clinicians should be alerted because of high expectations of this subgroup of patients, accustomed to emphasize the aesthetic result. LEVEL OF EVIDENCE V: This journal requires that the authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. PMID- 26857707 TI - Expanding roles of the hypoxia-response network in chronic kidney disease. AB - Studies over the last two decades have established tubulointerstitial hypoxia as a final common pathway leading to end-stage kidney disease (ESKD). Chronic kidney disease (CKD) is frequently associated with various degrees of hypoxic injury in distinct tubular segments, depending on the etiology and pathological stages, which constitutes an intricate link among inflammation, oxidative stress and fibrosis. Resident cells in the kidney are equipped with mechanisms through which they cope with hypoxia. Here, transcription of genes by hypoxia-inducible factors (HIFs) plays a central role. In the ischemic kidney, HIF-1 is expressed in tubular and glomerular epithelial cells and in papillary interstitial cells, whereas HIF-2 is expressed in endothelial cells and interstitial fibroblasts. There is ample evidence that HIF protects the kidney from acute ischemic damage. In CKD, studies suggest that the function of HIF may be suppressed because of factors, such as oxidative stress and uremia, which may underlie the pathogenesis of both CKD and co-existing problems, such as renal anemia. Based on these observations, efforts are in progress to test whether restoration and activation of HIF might protect the kidney from CKD. Initial studies using non-specific or supraphysiological HIF activation suggested that the role of HIF may be multifactorial and depend on pathological context. On the other hand, specific HIF stabilizers, such as prolyl hydroxylase (PHD) inhibitors, are being developed for the treatment of renal anemia. Application of these compounds in experimental CKD may override those previous findings and provide deeper insight into the roles of hypoxia and oxygen-sensing pathways. PMID- 26857709 TI - Accentuated hyperparathyroidism in type II Bartter syndrome. AB - BACKGROUND: Bartter syndrome (BS) may be associated with different degrees of hypercalciuria, but marked parathyroid hormone (PTH) abnormalities have not been described. METHODS: We compared clinical and laboratory data of patients with either ROMK-deficient type II BS (n = 14) or Barttin-deficient type IV BS (n = 20). RESULTS: Only BS-IV patients remained mildly hypokalemic in spite of a higher need for potassium supplementation. Estimated glomerular filtration rate (eGFR) was mildly decreased in only four BS-IV patients. Average PTH values were significantly higher in BS-II (160.6 +/- 85.8 vs. 92.5 +/- 48 pg/ml in BS-IV, p = 0.006). In both groups, there was a positive correlation between age and log(PTH). Levels of 25(OH) vitamin D were not different. Total serum calcium was lower (within normal limits) and age-related serum phosphate (Pi)-SDS was increased in BS-II (1.19 +/- 0.71 vs. 0.01 +/- 1.04 in BS-IV, p < 0.001). The GFR threshold for Pi reabsorption was higher in BS-II (5.63 +/- 1.25 vs. 4.36 +/- 0.98, p = 0.002). Spot urine calcium/creatinine ratio and nephrocalcinosis rate (100 vs. 16 %) were higher in the BS-II group. CONCLUSIONS: PTH, serum Pi levels, and urinary threshold for Pi reabsorption are significantly elevated in type II vs. type IV BS, suggesting a PTH resistance state. This may be a response to more severe long-standing hypercalciuria, leading to a higher rate of nephrocalcinosis in BS-II. PMID- 26857710 TI - A new approach to define acute kidney injury in term newborns with hypoxic ischemic encephalopathy. AB - BACKGROUND: Current definitions of acute kidney injury (AKI) are not sufficiently sensitive to identify all newborns with AKI during the first week of life. METHODS: To determine whether the rate of decline of serum creatinine (SCr) during the first week of life can be used to identify newborns with AKI, we reviewed the medical records of 106 term neonates at risk of AKI who were treated with hypothermia for hypoxic ischemic encephalopathy (HIE). RESULTS: Of the newborns enrolled in the study, 69 % showed a normal rate of decline of SCr to >=50 % and/or reached SCr levels of <=0.6 mg/dl before the 7th day of life, and therefore had an excellent clinical outcome (control group). Thirteen newborns with HIE (12 %) developed AKI according to an established neonatal definition (AKI-KIDGO group), and an additional 20 newborns (19 %) showed a rate of decline of SCr of <33, <40, and <46 % from birth to days 3, 5, or 7 of life, respectively (delayed rise in estimated SCr clearance group). Compared to the control group, newborns in the other two groups required more days of mechanical ventilation and vasopressor drugs and had higher gentamicin levels, more fluid overload, lower urinary epidermal growth factor levels, and a prolonged length of stay. CONCLUSIONS: The rate of decline of SCr provides a sensitive approach to identify term newborns with AKI during the first week of life. PMID- 26857711 TI - Perceived appetite and clinical outcomes in children with chronic kidney disease. AB - BACKGROUND: Children with chronic kidney disease (CKD) may have impaired caloric intake through a variety of mechanisms, with decreased appetite as a putative contributor. In adult CKD, decreased appetite has been associated with poor clinical outcomes. There is limited information about this relationship in pediatric CKD. METHODS: A total of 879 participants of the Chronic Kidney Disease in Children (CKiD) study were studied. Self-reported appetite was assessed annually and categorized as very good, good, fair, or poor/very poor. The relationship between appetite and iohexol or estimated glomerular filtration rate (ieGFR), annual changes in anthropometrics z-scores, hospitalizations, emergency room visits, and quality of life were assessed. RESULTS: An ieGFR < 30 ml/min per 1.73 m(2) was associated with a 4.46 greater odds (95 % confidence interval: 2.80, 7.09) of having a worse appetite than those with ieGFR >90. Appetite did not predict changes in height, weight, or BMI z-scores. Patients not reporting a very good appetite had more hospitalizations over the next year than those with a very good appetite. Worse appetite was significantly associated with lower parental and patient reported quality of life. CONCLUSIONS: Self-reported appetite in children with CKD worsens with lower ieGFR and is correlated with clinical outcomes, including hospitalizations and quality of life. PMID- 26857714 TI - Confronting climate change in the EMR: a win-win public health approach. PMID- 26857712 TI - Effect of elevated blood pressure on quality of life in children with chronic kidney disease. AB - BACKGROUND: Although hypertension is known to have an adverse impact on health related quality of life (HRQoL) in adults, little is known about the effects of hypertension and use of antihypertensive medications on HRQoL in hypertensive children with chronic kidney disease (CKD). METHODS: Cross-sectional and longitudinal assessment of impact of elevated blood pressure (BP) and antihypertensive medication use on HRQoL scores obtained in children enrolled in the Chronic Kidney Disease in Children (CKiD) Study. Blood pressure was measured both manually and by ambulatory blood pressure monitoring. HRQoL was assessed with the PedsQL survey. RESULTS: The study sample included 551 participants with sufficient data for cross-sectional and longitudinal analyses. Cross-sectional analysis of presence of prehypertension or hypertension and impact on HRQoL found mild associations between elevated BP and HRQoL scores with overall PedsQL parent and child scores averaging 79 vs. 76.5 and 83 vs. 78.5, respectively. However, no associations persisted under longitudinal multivariate analysis. CONCLUSIONS: Despite apparent small effects of elevated BP on HRQoL at baseline, no association was found between the presence of elevated BP and HRQoL over time in children with mild-to-moderate CKD. In addition, antihypertensive medication use did not appear to have an impact on HRQoL in this population. PMID- 26857715 TI - Prevalence of risk factors for noncommunicable diseases in Jalalabad city, Afghanistan, evaluated using the WHO STEPwise approach. AB - Noncommunicable diseases (NCDs) are a growing public health challenge. This study aimed to estimate the prevalence of common risk factors for NCDs among the adult population an urban setting in the eastern province of Nangarhar, Afghanistan. In a randomized, cluster sample survey of households the WHO STEPwise method was modified and used to collect demographic, behavioural and clinical data from 1200 adults (61% females) in Jalalabad in 2013. Blood samples were collected for biochemical testing. The prevalence of overweight/obesity, diabetes and hypertension were 57.4%, 11.4% and 24.4% respectively. Among respondents, 8.0% reported being current cigarette smokers and 13.7% used mouth snuff; 69.8% and 19.6% had < 3 servings of fruits and of vegetables respectively in a week; and 33.5% and 57.8% reported vigorous and moderate physical activity respectively. Tailored interventions on risk factors of NCDs are needed in urban areas in Afghanistan. PMID- 26857713 TI - Underlying genetic factors of the VATER/VACTERL association with special emphasis on the "Renal" phenotype. AB - The acronym VATER/VACTERL association (OMIM #192350) refers to the rare non random co-occurrence of the following component features (CFs): vertebral defects (V), anorectal malformations (A), cardiac defects (C), tracheoesophageal fistula with or without esophageal atresia (TE), renal malformations (R), and limb defects (L). According to epidemiological studies, the majority of patients with VATER/VACTERL association present with a "Renal" phenotype comprising a large spectrum of congenital renal anomalies. This finding is supported by evidence linking all of the human disease genes for the VATER/VACTERL association identified to date, namely, FGF8, FOXF1, HOXD13, LPP, TRAP1, and ZIC3, with renal malformations. Here we review these genotype-phenotype correlations and suggest that the elucidation of the genetic causes of the VATER/VACTERL association will ultimately provide insights into the genetic causes of the complete spectrum of congenital renal anomalies per se. PMID- 26857716 TI - Compliance with and knowledge about diabetes guidelines among physicians and nurses in Palestine. AB - Guidelines for the care of patients with diabetes mellitus are believed to improve clinical practice and patient care. This study aimed to analyse the pattern of diabetes care by physicians and nurses in primary care clinics in Palestine and their self-reported compliance with the local Palestinian guidelines. Questionnaires were used to collect data from 401 participants in 3 governorates in the West Bank. In total, 46.0% of participants knew about the existence of the Palestinian guidelines and about 60% believed these were partially used; 32.7% had received training on implementation of the guidelines. Multivariate analysis showed that training on the guidelines was the only factor significantly associated with self-reported compliance with guideline use. Respondents reported high commitment to the use of the guidelines, but their attitudes and behaviour varied with time constraints, availability of the guidelines, availability of laboratory tests and training on how to apply the guidelines. PMID- 26857717 TI - Study of prevalence and effects of insulin resistance in patients with chronic hepatitis C genotype 4. AB - There is strong epidemiological evidence linking hepatitis C virus (HCV) infection and diabetes. Our aim was to evaluate the prevalence of insulin resistance in Egyptian patients with chronic HCV genotype 4 infection, to assess factors associated with insulin resistance and to test the impact of insulin resistance on outcomes of treatment with pegylated interferon/ribavirin. Insulin resistance [homeostasis model assessmentinsulin resistance (HOMA-IR) score > 3.0] was detected in 31 of 100 nondiabetic patients. The relationship between elevated HOMA-IR and baseline viral load and degree of fibrosis was statistically significant (r = 0.218 and r = 0.223). Follow-up of patients with complete early virological response until the end of treatment showed a statistically significant decrease in HOMA-IR score. Out of 29 liver tissue sections examined, 14 had a low level of expression of insulin receptor type 1 by immunohistochemical studies. This study confirms that insulin resistance affects treatment outcome, and thus HOMA-IR testing before initiation of therapy may be a cost-effective tool. PMID- 26857718 TI - Trauma research in Qatar: a literature review and discussion of progress after establishment of a trauma research centre. AB - A structured research programme is one of the main pillars of a trauma care system. Despite the high rate of injury-related mortalities, especially road traffic accidents, in Qatar, little consideration has been given to research in trauma. This review aimed to analyse research publications on the subject of trauma published from Qatar and to discuss the progress of clinical research in Qatar and the Gulf Cooperation Council countries with special emphasis on trauma research. A literature search using PubMed and Google Scholar search engines located 757 English-language articles within the fields of internal medicine, surgery and trauma originating from Qatar between the years 1993 and 2013. A steep increase in the number of trauma publications since 2010 could be linked to the setting up of a trauma research centre in Qatar in 2011. We believe that establishing a research unit has made a major impact on research productivity, which ultimately benefits health care. PMID- 26857719 TI - Socioeconomic inequality and child maltreatment in Iranian schoolchildren. AB - Socioeconomic inequality and child maltreatment have not been studied using the concentration index as an indicator of inequality. The study aimed to assess the association of child maltreatment with socioeconomic status among schoolchildren in Qazvin province, Islamic Republic of Iran. In this cross-sectional study a questionnaire based on the ISPCAN Child Maltreatment Screening Tool-Children's Version and the Juvenile Victimization Questionnaire was filled by 1028 children aged 9-14 years, selected through multistage stratified random sampling. The concentration indices for economic inequality were -0.086 for any type of child maltreatment and -0.155, -0.098 and -0.139 for the physical, psychological and neglect subtypes of maltreatment respectively. The number of children and the economic status of the family also showed a significant association with child maltreatment in all 3 subtypes. Appropriate planning for effective interventions for at-risk children of lower socioeconomic status should be considered by the relevant decision-makers. PMID- 26857720 TI - Antibiogram of multidrug resistant Acinetobacter baumannii isolated from clinical specimens at King Hussein Medical Centre, Jordan: a retrospective analysis. AB - This study was conducted to determine the prevalence and the local antibiogram of multidrug-resistant Acinetobacter baumannii isolates in Al-Hussein Hospital at King Hussein Medical Centre in Amman, Jordan. In a retrospective study from January to December 2013, data on 116 non-repetitive positive clinical samples were retrieved from patients' laboratory records. The resistance rates of A. baumannii isolates were high for ceftriaxone, cefotaxime and ticarcillin (100%), ceftazidime, cefepime and piperacillin (98.3%), imipenem (97.4%), piperacillin/tazobactam (96.6%), quinolones (94.8%), ampicillin/sulbactam (89.7%), gentamicin, (87.9%), tobramycin and tetracycline (76.7%) and trimethoprim/sulfamethoxazole (75.9%), but lower for minocycline (26.7%) and colistin (1.7%). A. baumannii in our hospital were highly resistant to all antibiotics, including tigecycline, except for minocycline and colistin which are considered the last resort treatment for multidrug-resistant A. baumannii. PMID- 26857721 TI - Ageing and intergenerational family ties in Arab countries. AB - This paper explores the dominant issues in intergenerational ties in Arab countries with a view to highlighting patterns, trends and challenges as well as policy implications. The data were drawn from a review of scholarly work and published literature in Arab countries and from a regional mapping of ageing policies and programmes in 2012. Social and health ageing policies in the region have been set with the premise that the family represents the core safety net for older Arabs. Yet demographic, sociocultural and economic transitions, as well as political conflict in the Arab world, are bringing profound changes to familial structures. This review feeds into efforts to promote health and social reforms that approach intergenerational solidarity from several fronts: providing equitable old-age income security, fostering cross-generational interactions, embracing caregivers and home-based care, promoting age-responsive actions in emergencies and conflicts, and prioritizing context- and country-specific research on the levels, types and trends in intergenerational and familial support. PMID- 26857723 TI - WHO events addressing public health priorities. PMID- 26857722 TI - Jordan tobacco dependence treatment guidelines: rationale and development. AB - Jordan, a high tobacco-burden country, has been working to expand its tobacco dependence treatment services and has completed development of its first customized treatment guidelines. Our paper presents the development process for these guidelines. A group of national and international experts was formed and a national situation analysis for tobacco dependence treatment practices and a detailed review of international evidence were conducted. The guidelines were then drafted and reviewed by national, regional and international experts and were official endorsed by the Jordanian Ministry of Health before being launched. The guidelines comprise concise descriptions and practical supplementary flowcharts covering the major elements of general tobacco dependence treatment. These are the first comprehensive Arabic-language guidelines, including a section focusing on waterpipe use, and we believe they are a reliable and useful resource for neighbouring countries seeking to develop similar guidelines. PMID- 26857724 TI - Comparison of histopathological findings between idiopathic and secondary epiretinal membranes. AB - To evaluate the histopathological findings of idiopathic and secondary epithelial membranes (ERMs). This study involved 19 ERM cases that underwent pars plana vitrectomy (PPV). ERM specimens were obtained from each patient during PPV and immediately fixed in 10 % formalin. Paraffin sections were stained with hematoxylin eosin (HE) and immunohistochemical analysis was performed with glial fibrillary acidic protein (GFAP), Ki-67, CD34, and nestin antibodies. The 19 ERM cases included 11 idiopathic ERM cases and 8 secondary ERM cases i.e., 2 eyes that underwent PPV for retinal detachment and 6 eyes that underwent PPV for proliferative diabetic retinopathy. HE staining showed that some of the idiopathic ERM specimens consisted of internal limiting membrane. In contrast, numerous invasive cells were observed in the secondary ERM specimens compared to the idiopathic ERM specimens. Immunohistochemical analysis revealed GFAP-positive cells in 4 of the 11 idiopathic ERMs cases, yet no nestin-, Ki-67-, or CD34 positive cells in those cases. In contrast, there were 4 GFAP-positive cases, 2 Ki67-positive cases, 3 CD34-positive cases, and 7 cases including nestin-positive cells. The findings of this study indicate that there are different histological characteristics between idiopathic and secondary ERM and that mature nestin positive cells in the retina might be related to secondary ERM formation. PMID- 26857725 TI - Evaluation of the long-term results of trabectome surgery. AB - The aim of this study was to investigate the safety and efficacy of ab interno trabeculectomy which is a minimally invasive glaucoma surgery, in the late period, performed via trabectome instrument. A total of 70 eyes followed up with a diagnosis of open-angle glaucoma (OAG) and undertaken trabectome surgery were included in the study. Preoperative and postoperative intraocular pressures (IOPs), number of the drugs used, and complications were retrospectively investigated and the data were evaluated. The criteria of success were accepted as an IOP value <=21 mmHg or >=30 % reduction in IOP and no need for a second operation. Mean IOP was decreased by 38 % from a preoperative value of 28.77 +/- 5.34 to 17.62 +/- 2.81 mmHg at the end of 18 months. Likewise, mean drug usage was decreased by 48 % from a preoperative value of 3.3 +/- 1.01 to 1.7 +/- 1.16 at the end of 18 months. Both decreases were statistically significant (p < 0.05). Postoperative success rates were 82.8 % in the 6th month, 81.4 % in the 9th month, 77.1 % in the 12th month, and 70 % in the 18th month. Most common complication observed was intraoperative reflux hemorrhage and no serious complication was observed. Trabectome surgery is an effective and safe method in early-stage open-angle glaucoma types that cannot be controlled despite maximal medical therapy. This procedure is a proper surgical option in patients targeted for moderate IOP without the need for a topical medication or with less drug usage. PMID- 26857726 TI - Clostridium butyricum in combination with specific immunotherapy converts antigen specific B cells to regulatory B cells in asthmatic patients. AB - The effect of antigen specific immunotherapy (SIT) on asthma is supposed to be improved. Published data indicate that administration of probiotics alleviates allergic diseases. B cells play important roles in the pathogenesis of allergic diseases. This study aims to modulate antigen specific B cell property by the administration of Clostridium butyrate (CB) in combination with SIT. The results showed that after a 3-month treatment, the total asthma clinical score and serum specific IgE were improved in the patients treated with SIT, which was further improved in those treated with both SIT and CB, but not in those treated with CB alone. Treatment with SIT and CB increased p300 and STAT3 activation, up regulated the IL-10 gene transcription and increased the frequency of peripheral antigen specific B cells. In conclusion, administration with SIT in combination with CB converts Der p 1 specific B cells to regulatory B cells in asthma patients allergic to Der p 1. The data suggest a potential therapeutic remedy in the treatment of allergic diseases. PMID- 26857727 TI - Pre-cesarean Staphylococcus aureus nasal screening and decolonization: a prospective randomized controlled trial. AB - OBJECTIVE: Staphylococcus aureus (S. aureus) is a common pathogen in surgical site infections (SSIs). Mupirocin ointment is an effective treatment for nasal carriers. We aimed to investigate whether screening for nasal colonization of S. aureus and treating carriers prior to a cesarean section (CS) decreases the likelihood of SSI. METHODS: This is a randomized controlled trial. All participants underwent nasal culture prior to the CS. Nasal carriers of S. aureus were treated with Mupirocin ointment according to a standardized protocol. In the control group, nasal cultures were obtained immediately prior to surgery and carriers were not treated. RESULTS: We recruited 568 patients. Demographic characteristics were comparable between the groups. S. aureus nasal colonization rates were 20.1% and 14.9% in the intervention and control groups, respectively (p = 0.12). S. aureus eradication rate with Mupirocin treatment was 88%. SSI rates were similar in the intervention and control groups (13.1% versus 12.1%, respectively, p = 0.78) and in treated carriers, untreated carriers, and non carriers (7.4% versus 13.0% versus 13.1%, respectively, p = 0.69). Previous CS was the only factor found to independently predict SSI (OR 2.5, CI 1.09-5.65 p = 0.029). CONCLUSION: Pre-cesarean screening for nasal S. aureus carriage and decolonization does not appear to be an effective intervention in reducing SSI rates. PMID- 26857728 TI - Capsule Commentary on Gallo et al., Multimorbidity, Depression, and Mortality in Primary Care: Randomized Clinical Trial of an Evidence-Based Depression Care Management Program on Mortality Risk. PMID- 26857729 TI - Capsule Commentary on Genoff et al., Navigating Language Barriers: A Systematic Review of Patient Navigators' Impact on Cancer Screening for Limited English Proficient Patients. PMID- 26857730 TI - Capsule Commentary on Tosteson et al., Variation in Screening Abnormality Rates and Follow-Up of Breast, Cervical and Colorectal Cancer Screening within the PROSPR Consortium. PMID- 26857731 TI - Otologic Hazards Related to Scuba Diving. AB - CONTEXT: As of 2015, more than 23 million scuba diver certifications have been issued across the globe. Given the popularity of scuba diving, it is incumbent on every physician to know and understand the specific medical hazards and conditions associated with scuba diving. EVIDENCE ACQUISITION: Sources were obtained from PubMed, MEDLINE, and EBSCO databases from 1956 onward and ranged from diverse fields including otologic reviews and wilderness medicine book chapters. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 5. RESULTS: Otologic hazards can be categorized into barotrauma-related injuries or decompression sickness. CONCLUSION: When combined with a high index of suspicion, the physician can recognize these disorders and promptly initiate proper treatment of the potentially hazardous and irreversible conditions related to scuba diving. PMID- 26857732 TI - Preventing and Managing Hypothermia and Frostbite Injury. AB - CONTEXT: Hypothermia and frostbite injuries occur in cold weather activities and sporting events. EVIDENCE ACQUISITION: A PubMed search was used to identify original research and review articles related to cold, frostbite, and hypothermia. Inclusion was based on their relevance to prevention and treatment of cold-related injuries in sports and outdoor activities. Dates of review articles were limited to those published after 2010. No date limit was set for the most recent consensus statements or original research. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 5. RESULTS: Frostbite and hypothermia are well documented entities with good prevention strategies and prehospital treatment recommendations that have changed very little with time. A layered approach to clothing is the best way to prevent injury and respond to weather changes. Each athlete, defined as a participant in a cold weather sport or activity, will respond to cold differently depending on anthropometric measurements and underlying medical risk factors. An understanding of wind-chill temperatures, wetness, and the weather forecast allows athletes and event coordinators to properly respond to changing weather conditions. At the first sign of a freezing cold injury, ensure warm, dry clothes and move to a protected environment. CONCLUSION: Cold injuries can be prevented, and cold weather activities are safe with proper education, preparation, and response to changing weather conditions or injury. PMID- 26857733 TI - Influence of Adiposity, Physical Activity, Fitness, and Screen Time on Insulin Dynamics Over 2 Years in Children. AB - IMPORTANCE: Despite extensive evidence showing that lifestyle habits play a critical role in preventing or delaying the onset of type 2 diabetes in adults, little is known regarding the impact of lifestyle habits on type 2 diabetes risk in childhood. OBJECTIVE: To assess whether adiposity, fitness, moderate-to vigorous physical activity, and screen time predict insulin sensitivity or insulin secretion during a 2-year period in children with a family history of obesity. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective longitudinal cohort study of 630 children, having at least 1 obese parent, recruited from schools in Quebec, Canada, between July 2005 and December 2008 in the Quebec Adipose and Lifestyle Investigation in Youth (QUALITY) cohort. Children were assessed at baseline (ages 8-10 years) and 2 years later. Fitness was measured by peak oxygen consumption, percentage of body fat (adiposity) by dual-energy x-ray absorptiometry, moderate-to-vigorous physical activity using accelerometry, and screen time by average daily hours of self-reported television, video game, or computer use. Regression models were adjusted for age, sex, season, and pubertal stage. The current analysis was completed in October 2015. MAIN OUTCOMES AND MEASURES: Insulin sensitivity was measured by the homeostatic model assessment of insulin resistance and an oral glucose tolerance test-based index (Matsuda insulin sensitivity index). Insulin secretion was measured using the area under the curve of insulin to glucose during the first 30 minutes of the oral glucose tolerance test and using the area under the curve of insulin to glucose over 2 hours. RESULTS: Of 630 children evaluated at baseline (mean [SD] age, 9.6 [0.9] years; 54.4% male; 56.2% normal weight, 19.2% overweight, and 22.7% obese), 564 were evaluated at 2-year follow-up. Adiposity and changes in adiposity were the central predictors of insulin dynamics over time. Every additional 1% of body fat at ages 8 to 10 years decreased insulin sensitivity by 2.9% (95% CI, -3.3% to 2.5%; P < .001) and led to a 0.5% (95% CI, 0.09% to 0.8%; P = .02) increased requirement in the area under the curve of insulin to glucose during the first 30 minutes of the oral glucose tolerance test 2 years later. Higher levels of moderate-to-vigorous physical activity and lower screen time appear to be beneficial to insulin sensitivity in part through their effect on adiposity levels. CONCLUSIONS AND RELEVANCE: Adiposity plays a determining role in cardiometabolic health at a young age. Public health strategies that promote healthy body weight, notably physical activity, need to target school-aged and possibly younger children. PMID- 26857734 TI - Telomere length, genetic variants and risk of squamous cell carcinoma of the head and neck in Southeast Chinese. AB - Telomere dysfunction participates in malignant transformation and tumorigenesis. Previous studies have explored the associations between telomere length (TL) and cancer susceptibility; however, the findings are inconclusive. The associations between genetic variants and TL have been verified by quite a few genome-wide association studies (GWAS). Yet, to date, there was no published study on the relationship between TL, related genetic variants and susceptibility to squamous cell carcinoma of the head and neck (SCCHN) in Chinese. Hence, we detected relative telomere length (RTL) by using quantitative PCR and genotyped seven selected single nucleotide polymorphisms by TaqMan allelic discrimination assay in 510 SCCHN cases and 913 controls in southeast Chinese. The results showed that RTL was significantly associated with SCCHN risk [(adjusted odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.08-1.32, P = 0.001]. Furthermore, among seven selected SNPs, only G allele of rs2736100 related to RTL in Caucasians was significantly associated with both the decreased RTL (P = 0.002) and the increased susceptibility to SCCHN in Chinese (additive model: adjusted OR = 1.17, 95%CI = 1.00-1.38, P = 0.049). These findings provide evidence that shortened TL is a risk factor for SCCHN, and genetic variants can contribute to both TL and the susceptibility to SCCHN in southeast Chinese population. PMID- 26857735 TI - Genetics of autoimmune diseases: perspectives from genome-wide association studies. AB - Genome-wide association studies (GWASs) for autoimmune diseases (ADs) have identified many risk loci and have provided insights into the etiology of each disease. Some of these loci, such asPTPN22,IL23RandSTAT4, are shared among different ADs, and the combination of risk loci may determine an individual's susceptibility for a disease. The majority of GWAS loci are expression quantitative trait loci (eQTLs), where disease-causing variants regulate expression of neighboring (or sometimes distant) genes. Because the eQTL effects are often cell type-specific, the incorporation of epigenetic data from disease related cell types and tissues is expected to refine the identification of causal variants. The cumulative eQTL effects in multiple genes may influence the activity or fate of immune cells, which in turn may affect the function of the immune system in individuals. In this paper, I review the etiology of ADs by focusing on important immune cells (Th1 cells, Th17 cells and regulatory T cells), important pathways (antigen-receptor signaling and type I interferon signaling) and relevant genes identified in GWASs. PMID- 26857736 TI - IL-15 boosts the function and migration of human terminally differentiated CD8+ T cells by inducing a unique gene signature. AB - Human CCR7(low)CD45RA(high) effector memory CD8(+) T cells (terminally differentiated TEMRA) are reportedly a functionally compromised population with characteristics of cellular senescence when examined ex vivo Although their frequencies are increased in elderly subjects in association with declined immune competence, however, it remains unclear whether their impaired functions can be reversed so that they contribute to immune responses in vivo Here, I show that, in contrast to TCR stimulation, stimulation of TEMRA with IL-15 induced a unique transcriptional signature, promoted IFN-gamma production and cell cycle entry, and reduced chemotaxis toward sphingosine-1-phosphate (S1P). TEMRA preferentially accumulated in non-lymphoid tissues when transferred into IL-15-treated NOD.SCID.gammac-deficient mice compared with non-treated mice. This accumulation was impaired by S1P receptor 1 over-expression. These results suggest that TEMRA act as functional effector T cells in non-lymphoid tissues when IL-15 is abundant and that IL-15 treatment may be beneficial in enhancing vaccine efficacy in elderly people. PMID- 26857737 TI - Interactions fulvate-metal (Zn2+, Cu2+ and Fe2+): theoretical investigation of thermodynamic, structural and spectroscopic properties. AB - The use of theoretical calculation to determine structural properties of fulvate metal complex (zinc, copper and iron) is here related. The species were proposed in the ratio 1:1 and 2:1 for which the molecular structure was obtained through the semi-empirical method PM6. The calculation of thermodynamic stability ([Formula: see text]) predicted that the iron complex were more exo-energetic. Metallic ions were coordinated to the phtalate groups of the model-structure of fulvic acid Suwannee River and the calculations of vibrational frequencies suggested that hydrogen bonds may help on the stability of the complex formation. PMID- 26857738 TI - Manganese elevates manganese superoxide dismutase protein level through protein kinase C and protein tyrosine kinase. AB - Three experiments were conducted to investigate the effects of inorganic and organic Mn sources on MnSOD mRNA, protein and enzymatic activity and the possible signal pathways. The primary broiler myocardial cells were treated with MnCl2 (I) or one of organic chelates of Mn and amino acids with weak, moderate (M) or strong (S) chelation strength for 12 and 48 h. Cells were preincubated with superoxide radical anions scavenger N-acetylcysteine (NAC) or specific inhibitors for MAPKs and protein tyrosine kinase (PTK) or protein kinase C (PKC) for 30 min before treatments of I and M. The MnSOD mRNA, protein and enzymatic activity, phosphorylated MAPKs or protein kinases activations were examined. The results showed that additions of Mn increased (P < 0.05) MnSOD mRNA levels and M was more effective than I. Additions of Mn elevated (P < 0.05) MnSOD protein levels and enzymatic activities, and no differences were found among I and M. Addition of NAC did not decrease (P > 0.05) Mn-induced MnSOD mRNA and protein levels. None of the three MAPKs was phosphorylated (P > 0.05) by Mn. Additions of Mn decreased (P < 0.05) the PTK activities and increased (P < 0.05) the membrane PKC contents. Inhibitors for PTK or PKC decreased (P < 0.05) Mn-induced MnSOD protein levels. The results suggested that Mn-induced MnSOD mRNA and protein expressions be not related with NAC, and MAPK pathways might not involve in Mn-induced MnSOD mRNA expression. PKC and PTK mediated the Mn-induced MnSOD protein expression. PMID- 26857741 TI - Formic and Acetic Acids in Degradation Products of Plant Volatiles Elicit Olfactory and Behavioral Responses from an Insect Vector. AB - Volatile phytochemicals play a role in orientation by phytophagous insects. We studied antennal and behavioral responses of the Asian citrus psyllid, Diaphorina citri, vector of the citrus greening disease pathogen. Little or no response to citrus leaf volatiles was detected by electroantennography. Glass cartridges prepared with beta-ocimene or citral produced no response initially but became stimulatory after several days. Both compounds degraded completely in air to a number of smaller molecules. Two peaks elicited large antennal responses and were identified as acetic and formic acids. Probing by D. citri of a wax substrate containing odorants was significantly increased by a blend of formic and acetic acids compared with either compound separately or blends containing beta-ocimene and/or citral. Response surface modeling based on a 4-component mixture design and a 2-component mixture-amount design predicted an optimal probing response on wax substrate containing a blend of formic and acetic acids. Our study suggests that formic and acetic acids play a role in host selection by D. citri and perhaps by phytophagous insects in general even when parent compounds from which they are derived are not active. These results have implications for the investigation of arthropod olfaction and may lead to elaboration of attract-and kill formulations to reduce nontarget effects of chemical control in agriculture. PMID- 26857742 TI - How Many and Which Odor Identification Items Are Needed to Establish Normal Olfactory Function? AB - The establishment of normal olfactory function by means of a simple and reliable test is one method that could minimize olfactory test procedures in the clinic. This retrospective study analyzed the identification of 16 odors by 613 subjects (aged 18-96 years, 266 men) as a part of a complex olfactory test battery by which 183, 251, and 179 subjects were diagnosed with anosmia, hyposmia, or normosmia, respectively. Cinnamon was identified as the best scoring odor, that is, identified correctly by most normosmic subjects, but identified correctly by the fewest anosmic patients. An exact calculation of the optimum number of items needed for a diagnosis of normosmia resulted in 1 single odor identification item as being sufficient. The inclusion of more items is solely determined by the acceptable proportion of chance, which in a 4-alternative forced choice paradigm is only 1.6% with 3 odors. A proposed screening test using cinnamon, fish odor, and banana established normosmia at a sensitivity of 80.4% and a specificity of 84.3% and a negative predictive value of 91.3%.A positive test result reliably establishes normosmia providing a confidence basis to terminate olfactory assessments following the application of only 3 odor identification items. PMID- 26857739 TI - Incidence of register-based diabetes 10 years after a stepwise diabetes screening programme: the ADDITION-Denmark study. AB - AIMS/HYPOTHESIS: Screening programmes for type 2 diabetes inevitably find more people at high risk of developing diabetes than people with undiagnosed prevalent diabetes. We describe the incidence of diabetes for risk groups according to advancement in a screening process. METHODS: In 2001-2006, a diabetes screening programme based on the Danish diabetes risk score and measures of HbA1c and glucose was carried out in Danish general practices. The present study includes 13,249 individuals with low diabetes risk scores and 22,726 with high diabetes risk scores but no diabetes according to WHO 1999 criteria. Seven incremental levels of diabetes risk were defined and followed for incident diabetes recorded in the Danish National Diabetes Register until December 2012. For each group, cumulative diabetes incidence was calculated. Incidence rates and rate ratios were estimated by Poisson regression analyses. RESULTS: After 10 years of follow up 1,164 new diabetes cases were registered. Incidence rates were 1.0, 4.2, 14.5, 28.8 and 52.6 per 1,000 person-years in individuals at low risk and in those with normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance and one diabetic glucose value, respectively. For each step in the screening algorithm, the risk of developing diabetes was higher than in the previous step. CONCLUSIONS/INTERPRETATION: The risk of developing clinical diabetes in people who screen negative for diabetes depends on the level of risk stratification at screening, even at lower risk levels. This risk increases markedly in the presence of impaired glucose regulation. These results can inform policy recommendations concerning prevention strategies following screening. PMID- 26857743 TI - Comparative Benefits and Harms of Antidepressant, Psychological, Complementary, and Exercise Treatments for Major Depression: An Evidence Report for a Clinical Practice Guideline From the American College of Physicians. AB - BACKGROUND: Primary care patients and clinicians may prefer options other than second-generation antidepressants for the treatment of major depressive disorder (MDD). The comparative benefits and harms of antidepressants and alternative treatments are unclear. PURPOSE: To compare the benefits and harms of second generation antidepressants and psychological, complementary and alternative medicine (CAM), and exercise treatments as first- and second-step interventions for adults with acute MDD. DATA SOURCES: English-, German-, and Italian-language studies from multiple electronic databases (January 1990 to September 2015); trial registries and gray-literature databases were used to identify unpublished research. STUDY SELECTION: Two investigators independently selected comparative randomized trials of at least 6 weeks' duration on health outcomes of adult outpatients; nonrandomized studies were eligible for harms. DATA EXTRACTION: Reviewers abstracted data on study design, participants, interventions, and outcomes; rated the risk of bias; and graded the strength of evidence. A senior reviewer confirmed data and ratings. DATA SYNTHESIS: 45 trials met inclusion criteria. On the basis of moderate-strength evidence, cognitive behavioral therapy (CBT) and antidepressants led to similar response rates (relative risk [RR], 0.90 [95% CI, 0.76 to 1.07]) and remission rates (RR, 0.98 [CI, 0.73 to 1.32]). In trials, antidepressants had higher risks for adverse events than most other treatment options; no information from nonrandomized studies was available. The evidence was too limited to make firm conclusions about differences in the benefits and harms of antidepressants compared with other treatment options as first-step therapies for acute MDD. For second-step therapies, different switching and augmentation strategies provided similar symptom relief. LIMITATION: High dropout rates, dosing inequalities, small sample sizes, and poor assessment of adverse events limit confidence in the evidence. CONCLUSION: Given their similar efficacy, CBT and antidepressants are both viable choices for initial treatment of MDD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. PMID- 26857746 TI - SOME USES OF MODELS OF QUANTITATIVE GENETIC SELECTION IN SOCIAL SCIENCE. AB - The theory of selection of quantitative traits is widely used in evolutionary biology, agriculture and other related fields. The fundamental model known as the breeder's equation is simple, robust over short time scales, and it is often possible to estimate plausible parameters. In this paper it is suggested that the results of this model provide useful yardsticks for the description of social traits and the evaluation of transmission models. The differences on a standard personality test between samples of Old Order Amish and Indiana rural young men from the same county and the decline of homicide in Medieval Europe are used as illustrative examples of the overall approach. It is shown that the decline of homicide is unremarkable under a threshold model while the differences between rural Amish and non-Amish young men are too large to be a plausible outcome of simple genetic selection in which assortative mating by affiliation is equivalent to truncation selection. PMID- 26857744 TI - Astrocyte-to-neuron intercellular prion transfer is mediated by cell-cell contact. AB - Prion diseases are caused by misfolding of the cellular protein PrP(C) to an infectious conformer, PrP(Sc). Intercellular PrP(Sc) transfer propagates conversion and allows infectivity to move from the periphery to the brain. However, how prions spread between cells of the central nervous system is unclear. Astrocytes are specialized non-neuronal cells within the brain that have a number of functions indispensable for brain homeostasis. Interestingly, they are one of the earliest sites of prion accumulation in the brain. A fundamental question arising from this observation is whether these cells are involved in intercellular prion transfer and thereby disease propagation. Using co-culture systems between primary infected astrocytes and granule neurons or neuronal cell lines, we provide direct evidence that prion-infected astrocytes can disseminate prion to neurons. Though astrocytes are capable of secreting PrP, this is an inefficient method of transferring prion infectivity. Efficient transfer required co-culturing and direct cell contact. Astrocytes form numerous intercellular connections including tunneling nanotubes, containing PrP(Sc), often colocalized with endolysosomal vesicles, which may constitute the major mechanism of transfer. Because of their role in intercellular transfer of prions astrocytes may influence progression of the disease. PMID- 26857745 TI - Attenuation of ligand-induced activation of angiotensin II type 1 receptor signaling by the type 2 receptor via protein kinase C. AB - Angiotensin II (AII) type 2 receptor (AT2R) negatively regulates type 1 receptor (AT1R) signaling. However, the precise molecular mechanism of AT2R-mediated AT1R inhibition remains poorly understood. Here, we characterized the local and functional interaction of AT2R with AT1R. AT2R colocalized and formed a complex with AT1R at the plasma membrane, even in the absence of AII. Upon AII stimulation, the spatial arrangement of the complex was modulated, as confirmed by Forster resonance energy transfer (FRET) analysis, followed by AT2R internalization along with AT1R. AT2R internalization was specifically observed only in the presence of AT1R; AT2R alone could not be internalized. The AT1R specific inhibitor losartan completely inhibited both the conformational change and the internalization of AT2R with AT1R, whereas the AT2R-specific inhibitor PD123319 partially hindered these phenomena, demonstrating that the activation of both receptors was indispensable for these effects. In addition, treatment with the protein kinase C (PKC) inhibitors inhibited the ligand-dependent accumulation of AT2R but not that of AT1R in the endosomes. A mutation in the putative phosphorylation sites of AT2R also abrogated the co-internalization of ATR2 with AT1R and the inhibitory effect of ATR2 on AT1R. These data suggest that AT2R inhibits ligand-induced AT1R signaling through the PKC-dependent pathway. PMID- 26857749 TI - A new milestone for Palliative & Supportive Care. PMID- 26857748 TI - Gold nanoparticle-assisted all optical localized stimulation and monitoring of Ca2+ signaling in neurons. AB - Light-assisted manipulation of cells to control membrane activity or intracellular signaling has become a major avenue in life sciences. However, the ability to perform subcellular light stimulation to investigate localized signaling has been limited. Here, we introduce an all optical method for the stimulation and the monitoring of localized Ca(2+) signaling in neurons that takes advantage of plasmonic excitation of gold nanoparticles (AuNPs). We show with confocal microscopy that 800 nm laser pulse application onto a neuron decorated with a few AuNPs triggers a transient increase in free Ca(2+), measured optically with GCaMP6s. We show that action potentials, measured electrophysiologically, can be induced with this approach. We demonstrate activation of local Ca(2+) transients and Ca(2+) signaling via CaMKII in dendritic domains, by illuminating a single or few functionalized AuNPs specifically targeting genetically-modified neurons. This NP-Assisted Localized Optical Stimulation (NALOS) provides a new complement to light-dependent methods for controlling neuronal activity and cell signaling. PMID- 26857747 TI - Robotic lower limb prosthesis design through simultaneous computer optimizations of human and prosthesis costs. AB - Robotic lower limb prostheses can improve the quality of life for amputees. Development of such devices, currently dominated by long prototyping periods, could be sped up by predictive simulations. In contrast to some amputee simulations which track experimentally determined non-amputee walking kinematics, here, we explicitly model the human-prosthesis interaction to produce a prediction of the user's walking kinematics. We obtain simulations of an amputee using an ankle-foot prosthesis by simultaneously optimizing human movements and prosthesis actuation, minimizing a weighted sum of human metabolic and prosthesis costs. The resulting Pareto optimal solutions predict that increasing prosthesis energy cost, decreasing prosthesis mass, and allowing asymmetric gaits all decrease human metabolic rate for a given speed and alter human kinematics. The metabolic rates increase monotonically with speed. Remarkably, by performing an analogous optimization for a non-amputee human, we predict that an amputee walking with an appropriately optimized robotic prosthesis can have a lower metabolic cost--even lower than assuming that the non-amputee's ankle torques are cost-free. PMID- 26857751 TI - Transcriptomic investigation of meat tenderness in two Italian cattle breeds. AB - Our objectives for this study were to understand the biological basis of meat tenderness and to provide an overview of the gene expression profiles related to meat quality as a tool for selection. Through deep mRNA sequencing, we analyzed gene expression in muscle tissues of two Italian cattle breeds: Maremmana and Chianina. We uncovered several differentially expressed genes that encode for proteins belonging to a family of tripartite motif proteins, which are involved in growth, cell differentiation and apoptosis, such as TRIM45, or play an essential role in regulating skeletal muscle differentiation and the regeneration of adult skeletal muscle, such as TRIM32. Other differentially expressed genes (SCN2B, SLC9A7 and KCNK3) emphasize the involvement of potassium-sodium pumps in tender meat. By mapping splice junctions in RNA-Seq reads, we found significant differences in gene isoform expression levels. The PRKAG3 gene, which is involved in the regulation of energy metabolism, showed four isoforms that were differentially expressed. This distinct pattern of PRKAG3 gene expression could indicate impaired glycogen storage in skeletal muscle, and consequently, this gene very likely has a role in the tenderization process. Furthermore, with this deep RNA-sequencing, we captured a high number of expressed SNPs, for example, we found 1462 homozygous SNPs showing the alternative allele with a 100% frequency when comparing tender and tough meat. SNPs were then classified into categories by their position and also by their effect on gene coding (174 non-synonymous polymorphisms) based on the available UMD_3.1 annotations. PMID- 26857750 TI - Berberine prevents progression from hepatic steatosis to steatohepatitis and fibrosis by reducing endoplasmic reticulum stress. AB - The histological spectrum of nonalcoholic fatty liver diseases (NAFLD) ranges from hepatic steatosis to steatohepatitis and fibrosis. Berberine (BBR) is known for its therapeutic effect on obesity, hyperglycaemia and dyslipidaemia; however, its effect on NAFLD has yet to be thoroughly explored. Db/db mice and methionine choline-deficient diet-fed mice were administered BBR via gavage. We found that BBR-treated mice were more resistant to steatosis in the liver than vehicle treated mice and that BBR significantly reduced hepatic inflammation, fibrosis and lipid peroxides. The beneficial effect of BBR was associated with suppressing endoplasmic reticulum (ER) stress. Additionally, BBR decreased the free fatty acid-induced lipid accumulation and tunicamycin-induced ER stress in primary hepatocytes and hepatocyte cell lines. We demonstrated that BBR exhibited chaperone activity, reduced protein aggregation in vitro and alleviated tunicamycin-induced triglyceride and collagen deposition in vivo. Finally, we showed that BBR could reverse ER stress-activated lipogenesis through the ATF6/SREBP-1c pathway in vitro. These results indicated that BBR may be a new therapeutic strategy against hepatic steatosis and non-alcoholic steatohepatitis. PMID- 26857752 TI - "I hate being a burden": The patient perspective on carer burden in amyotrophic lateral sclerosis. AB - Research has shown that family caregivers of ALS patients encounter carer burden. Studies that have investigated the impact of caring on family in ALS have reported predominantly from the family caregiver perspective. We undertook in depth qualitative interviews with a diverse group of ALS patients (n = 34) sampled from the Irish ALS population-based register and explored their experiences of receiving care from family members and from formal service providers. Interviews were audio recorded and transcribed and data were coded to identify psychosocial processes. Findings showed that patients perceived their care as a burden on family and had concerns about the adverse effects that caring had on family caregivers. However, participants also resisted being a burden on family and they provided emotional support to their family. Participants felt a strong sense of obligation towards family and their concern about family members shaped their expressed preferences for care. We identified that the caring process between ALS patients and their family is often bi-directional, leading in some cases to the patient experiencing carer burden. In conclusion, greater attention in ALS research and practice to patients' supportive roles in family is required to counterbalance the already strong focus on family caregiver burden. PMID- 26857753 TI - Public health nutrition capacity: assuring the quality of workforce preparation for scaling up nutrition programmes. AB - OBJECTIVE: To describe why and how capacity-building systems for scaling up nutrition programmes should be constructed in low- and middle-income countries (LMIC). DESIGN: Position paper with task force recommendations based on literature review and joint experience of global nutrition programmes, public health nutrition (PHN) workforce size, organization, and pre-service and in service training. SETTING: The review is global but the recommendations are made for LMIC scaling up multisectoral nutrition programmes. SUBJECTS: The multitude of PHN workers, be they in the health, agriculture, education, social welfare, or water and sanitation sector, as well as the community workers who ensure outreach and coverage of nutrition-specific and -sensitive interventions. RESULTS: Overnutrition and undernutrition problems affect at least half of the global population, especially those in LMIC. Programme guidance exists for undernutrition and overnutrition, and priority for scaling up multisectoral programmes for tackling undernutrition in LMIC is growing. Guidance on how to organize and scale up such programmes is scarce however, and estimates of existing PHN workforce numbers - although poor - suggest they are also inadequate. Pre-service nutrition training for a PHN workforce is mostly clinical and/or food science oriented and in-service nutrition training is largely restricted to infant and young child nutrition. CONCLUSIONS: Unless increased priority and funding is given to building capacity for scaling up nutrition programmes in LMIC, maternal and child undernutrition rates are likely to remain high and nutrition-related non-communicable diseases to escalate. A hybrid distance learning model for PHN workforce managers' in-service training is urgently needed in LMIC. PMID- 26857754 TI - Abnormal transcranial Doppler cerebral blood flow velocity and blood pressure profiles in children with syndromic craniosynostosis and papilledema. AB - OBJECTIVE: Children with syndromic craniosynostosis are at risk of intracranial hypertension. This study aims to examine patient profiles of transcranial Doppler (TCD) cerebral blood flow velocity (CBFv) and systemic blood pressure (BP) in subjects with and without papilledema at the time of surgery, and subsequent effect of cranial vault expansion. METHODS: Prospective study of patients treated at a national referral center. Patients underwent TCD of the middle cerebral artery 1 day before and 3 weeks after surgery. Measurements included mean CBFv, peak systolic velocity, and end diastolic velocity; age-corrected resistive index (RI) was calculated. Systemic BP was recorded. Papilledema was used to indicate intracranial hypertension. RESULTS: Twelve patients (mean age 3.1 years, range 0.4-9.5) underwent TCD; 6 subjects had papilledema. Pre-operatively, patients with papilledema, in comparison to those without, had higher TCD values, RI, and BP (all p = 0.04); post-operatively, the distinction regarding BP remained (p = 0.04). There is a significant effect of time following vault surgery with a decrease in RI (p < 0.01). CONCLUSION: Patients with syndromic craniosynostosis who have papilledema have a different TCD profile with raised BP. Vault surgery results in increased CBFv and decrease in RI, however the associated systemic BP response to intracranial hypertension remained at short-term follow-up. PMID- 26857755 TI - The role of mylohyoid flap in the treatment of bisphosphonate-related osteonecrosis of the jaws. AB - INTRODUCTION: Surgical treatment of bisphosphonate-related osteonecrosis of the jaws (BRONJ) combines excision of adequate damaged bone and watertight coverage by appropriate vascularized tissue. Local tissues are preferred when possible. This study compares local mucoperiosteal flaps with mylohyoid flaps with special emphasis on their influence on wound healing. MATERIAL AND METHODS: A total of 195 patients with BRONJ in the mandible were included in this prospective study. The control group (n = 169) were treated with a mucoperiosteal flap, whereas patients of the study group (n = 26) received a mylohyoid flap. RESULTS: Recurrence of BRONJ was significantly reduced (p = 0.023) as was extent of necrosis (p = 0.001) in patients with mylohyoid flaps. DISCUSSION: This study demonstrates the importance of a sufficient mucosal coverage in surgical treatment of BRONJ. The mylohyoid flap provides an additional tissue coverage, which seems to account for the significantly reduced rate of disease recurrence. CONCLUSION: The vascularized mylohyoid flap is an important tool in the complex and challenging surgical care of BRONJ. PMID- 26857756 TI - Satisfactory surgical option for cartilage graft absorption in microtia reconstruction. AB - BACKGROUND: We routinely perform auricular elevation at least 6 months after implantation of framework in microtia reconstruction using costal cartilage. However, in a few cases, cartilage graft absorption has occurred, which has led to contour irregularity with unfavorable long-term results. In the present study, we recount the details of using additional rib cartilage augmentation to achieve an accentuated contour in cartilage graft absorption cases. MATERIAL AND METHODS: The cartilage graft absorption was defined as contour irregularity or cartilage graft deformation as evaluated by the surgeon and patient. Depending on the extent of cartilage graft absorption, another rib cartilage framework was added to the previously implanted framework, targeting the absorption area. We used banked cartilage or harvested new cartilage based on three-dimensional rib computed tomography. RESULTS: Additional recontouring of framework was conducted in eight patients who were examined for cartilage graft absorption from 1.5 to 5 years after implantation of the framework. Four patients received additional rib cartilage augmentation and tissue expander insertion simultaneously prior to auricular elevation. Two patients underwent auricular elevation simultaneously. In another two patients, additional rib cartilage augmentation was performed before auricular elevation. The mean follow-up period was 18 months, and in all cases reconstructive results were acceptable. CONCLUSIONS: Although further follow-up evaluation is required, additional rib cartilage augmentation is an attractive surgical option for cartilage graft absorption cases. PMID- 26857757 TI - In vivo biofunctionalization of titanium patient-specific implants with nano hydroxyapatite and other nano calcium phosphate coatings: A systematic review. AB - OBJECTIVE: To delineate the best procedures for increasing osseointegration in cranio-maxillo-facial surgery using nano-sized calcium phosphate coatings on titanium patient specific implants. MATERIALS AND METHODS: A multi-database single-reviewer systematic literature review was conducted. RESULTS: Twenty-eight papers consisting of twenty-five animal studies and three human studies met the selection criteria. The results of existing literature suggest that titanium implants coated with nano calcium phosphate and hydroxyapatite improves osseointegration and implant fixation. However, not all coating techniques enhance biofunctionalization. Factors including implant microroughness, coating thickness, calcium phosphate solubility, and nanotopography contribute significantly to biofunctionalization. Nonetheless, additional data derived from clinical studies are needed to support this statement, as well as the possible influence of routine autoclaving procedures. PMID- 26857758 TI - Middle ear findings and need for ventilation tubes among pediatric cleft lip and palate patients in northern Finland. AB - PURPOSE: Middle ear problems are common in cleft patients. This study aimed to determine the need for ventilation tubes (VTs) and complications such as tympanic perforation and cholesteatoma. MATERIAL AND METHODS: Data of 156 children with clefts managed in northern Finland spanning 15 years from 1997 to 2011 were collected from 6 hospitals. The following were recorded: birth date, gender, cleft type, surgery timing, surgery type, number of tube insertions, tube material, middle ear findings, and tube placement timing. Clefts were divided into 4 groups: cleft palate (CP), cleft lip and palate (CLP), cleft lip (CL), and submucous cleft palate. The prevalence of middle ear findings was reported. RESULTS: Mucous secretion was noted in 96.8% of CLP patients, 69.2% of CP patients, and 13.0% of CL patients. In all, 82.7% of study group had 1 or more VTs placed during follow-up. All CLP patients required more than 1 VT placement. A total of 94.5% of CP patients required VTs compared to 13.0% of CL patients. In the presence of residual oral nasal fistula, the mean number of tube insertions was 5.3. The prevalence of tympanic perforations in clefts was 35.9% and cholesteatoma in 2.6% of patients. CONCLUSIONS: CLP and isolated CP patients have frequent middle ear infections requiring multiple VT placements. PMID- 26857759 TI - Donor site morbidity of anterior iliac crest and calvarium bone grafts: A comparative case-control study. AB - PURPOSE: Notwithstanding its donor site morbidity, autogenous bone graft harvesting is still considered the gold standard for cases of extreme resorption of the alveolar ridge. The aim of this study was to assess donor site morbidity of calvarium and anterior iliac crest harvesting. MATERIAL AND METHODS: A total of 27 edentulous patients who had undergone calvarial bone harvesting were matched with 27 edentulous patients in which anterior iliac crest bone was harvested. All patients had been treated between March 2011 and December 2013. Patients were matched according to age, sex, and duration of follow-up. Donor site morbidity was assessed by medical records, patient questionnaires, and physical examination. Patients were recalled to assess persisting morbidity of the harvesting procedure. RESULTS: Exposure of the dura occurred in three patients in the calvarial group. Postoperative pain (based on a visual analog scale) after harvesting was significantly higher in the anterior iliac crest group. Scars were significantly longer and contours deficits were significantly more prominent after calvarial harvesting, although not bothersome to the patients. Long-term pain was negligible in both groups, and satisfaction with the procedure did not differ. CONCLUSION: Both harvesting techniques were accompanied by low long-term donor site morbidity and high patient satisfaction. PMID- 26857760 TI - Invasive fungal rhinosinusitis in adult patients: Our experience in diagnosis and management. AB - BACKGROUND: This paper describes our experience in the management of acute and chronic invasive fungal rhinosinusitis (IFRS) in adults. METHODS: Medical files of all patients aged >18 years treated in our institutions for IFRS from 2002 to 2013 were retrospectively reviewed. RESULTS: A total of 18 cases (10 acute and 8 chronic) were recorded. In acute form, haematological malignancies represented the principal comorbidity (100%), while in chronic form this was diabetes mellitus (87.5%). All patients received systemic antifungal agents. Endoscopic sinus surgery was performed in 16/18 patients (88.9%). Among patients with an acute IFRS, 4/10 died of fungal infection (40%), on the other side 2/8 patients with chronic IFRS died of the evolution of the mycosis (25%). CONCLUSIONS: Acute and chronic IFRS are different entities: in acute form, prognosis is poor, so therapy should be promptly performed, although host immune status and evolution of the haematological disease are key factors for the outcome. In chronic form, a wide surgical excision of the disease is recommended in order to obtain a complete removal of fungal infection. In both forms, early clinical findings are non-specific and ambiguous, so diagnosis depends on a high index of suspicion, taking into account predisposing factors. PMID- 26857761 TI - Flaxseed reduces epithelial proliferation but does not affect basal cells in induced benign prostatic hyperplasia in rats. AB - PURPOSE: This study aimed to quantitatively and qualitatively evaluate the effects of a flaxseed-based diet on the histoarchitecture of the prostate of normal Wistar rats and of rats with induced BPH. METHODS: The study included four experimental groups of ten animals each: casein control group (CCG), who were fed a casein-based diet; flaxseed control group (FCG), who were fed a flaxseed-based diet; hyperplasia-induced casein group (HICG), who were fed a casein-based diet; and hyperplasia-induced flaxseed group (HIFG), who were fed a flaxseed-based diet. Hyperplasia was induced by the subcutaneous implantation of silicone pellets containing testosterone propionate. After 20 weeks, the rats were euthanized and their prostate fixed in buffered formalin. Tissue sections were stained with HE, picrosirius red and immunostained for nuclear antigen p63. Histomorphometric analysis evaluated the epithelial thickness, epithelial area, individual luminal area, and total area of prostatic alveoli. RESULTS: The mean epithelial thickness obtained for HIFG and HICG was 16.52 +/- 1.65 and 20.58 +/- 2.86 um, respectively. The mean epithelial thickness in HICG was greater than that in the other groups tested. HIFG had a smaller epithelial thickness and lower percentage of papillary projections in the prostatic alveoli. No significant difference was observed between CCG and FCG. The total area and mean alveolar area showed no significant differences between the groups. The number of cells immunostained for p63 was not significantly different between the groups evaluated. CONCLUSION: These results suggest that flaxseed has a protective effect on the prostate epithelium in BPH-induced animals. PMID- 26857763 TI - Epidemiology of Cystic Fibrosis. AB - Improved quality of care and rapidly emerging therapeutic strategies to restore chloride transport profoundly impact the epidemiology and pathobiology of cystic fibrosis (CF) in the twenty-first century. CF now serves as a model for chronic illness management, continuous quality improvement via registry data, and a seamless link between basic science research, translational studies, clinical trials, and outcomes research to enable rapid expansion of treatment options. PMID- 26857764 TI - Genetics of Cystic Fibrosis: Clinical Implications. AB - Cystic fibrosis (CF) is a common life-shortening autosomal recessive genetic disorder caused by mutations in the gene that encodes for the cystic fibrosis transmembrane conductance regulator protein (CFTR). Almost 2000 variants in the CFTR gene have been identified. The mutational classes are based on the functional consequences on CFTR. New therapies are being developed to target mutant CFTR and restore CFTR function. Understanding specific CF genotypes is essential for providing state-of-the art care to patients. In addition to the variation in CFTR genotype, there are several modifier genes that contribute to the respiratory phenotype. PMID- 26857762 TI - Difference in postprandial GLP-1 response despite similar glucose kinetics after consumption of wheat breads with different particle size in healthy men. AB - PURPOSE: Underlying mechanisms of the beneficial health effects of low glycemic index starchy foods are not fully elucidated yet. We varied the wheat particle size to obtain fiber-rich breads with a high and low glycemic response and investigated the differences in postprandial glucose kinetics and metabolic response after their consumption. METHODS: Ten healthy male volunteers participated in a randomized, crossover study, consuming 13C-enriched breads with different structures; a control bread (CB) made from wheat flour combined with wheat bran, and a kernel bread (KB) where 85 % of flour was substituted with broken wheat kernels. The structure of the breads was characterized extensively. The use of stable isotopes enabled calculation of glucose kinetics: rate of appearance of exogenous glucose, endogenous glucose production, and glucose clearance rate. Additionally, postprandial plasma concentrations of glucose, insulin, glucagon, incretins, cholecystokinin, and bile acids were analyzed. RESULTS: Despite the attempt to obtain a bread with a low glycemic response by replacing flour by broken kernels, the glycemic response and glucose kinetics were quite similar after consumption of CB and KB. Interestingly, the glucagon like peptide-1 (GLP-1) response was much lower after KB compared to CB (iAUC, P < 0.005). A clear postprandial increase in plasma conjugated bile acids was observed after both meals. CONCLUSIONS: Substitution of 85 % wheat flour by broken kernels in bread did not result in a difference in glucose response and kinetics, but in a pronounced difference in GLP-1 response. Thus, changing the processing conditions of wheat for baking bread can influence the metabolic response beyond glycemia and may therefore influence health. PMID- 26857765 TI - Innate and Adaptive Immunity in Cystic Fibrosis. AB - Cystic fibrosis (CF) lung disease is characterized by persistent and unresolved inflammation, with elevated proinflammatory and decreased anti-inflammatory cytokines, and greater numbers of immune cells. Hyperinflammation is recognized as a leading cause of lung tissue destruction in CF. Hyper-inflammation is not solely observed in the lungs of CF patients, since it may contribute to destruction of exocrine pancreas and, likely, to defects in gastrointestinal tract tissue integrity. Paradoxically, despite the robust inflammatory response, and elevated number of immune cells (such as neutrophils and macrophages), CF lungs fail to clear bacteria and are more susceptible to infections. Here, we have summarized the current understanding of immune dysregulation in CF, which may drive hyperinflammation and impaired host defense. PMID- 26857766 TI - Diagnostic Testing in Cystic Fibrosis. AB - Cystic Fibrosis (CF) is a rare, multisystem disease leading to significant morbidity and mortality. CF is caused by defects in the cystic fibrosis transmembrane conductance regulator protein (CFTR), a chloride and bicarbonate transporter. Early diagnosis and access to therapies provides benefits in nutrition, pulmonary health, and cognitive ability. Several screening and diagnostic tests are available to support a diagnosis. We discuss the characteristics of screening and diagnostic tests for CF and guideline-based algorithms using these tools to establish a diagnosis. We discuss classification and management of common "diagnostic dilemmas," including the CFTR-related metabolic syndrome and other CFTR-associated diseases. PMID- 26857767 TI - Diagnosis of Adult Patients with Cystic Fibrosis. AB - The diagnosis of cystic fibrosis (CF) is being made with increasing frequency in adults. Patients with CF diagnosed in adulthood typically present with respiratory complaints, and often have recurrent or chronic airway infection. At the time of initial presentation individuals may appear to have clinical manifestation limited to a single organ, but with subclinical involvement of the respiratory tract. Adult-diagnosed patients have a good response to CF center care, and newly available cystic fibrosis transmembrane receptor-modulating therapies are promising for the treatment of residual function mutation, thus increasing the importance of the diagnosis in adults with unexplained bronchiectasis. PMID- 26857769 TI - The Approach to Pseudomonas aeruginosa in Cystic Fibrosis. AB - There is a high prevalence of Pseudomonas aeruginosa in patients with cystic fibrosis and clear epidemiologic links between chronic infection and morbidity and mortality exist. Prevention and early identification of infection are critical, and stand to improve with the advent of new vaccines and laboratory methods. Once the organism is identified, a variety of treatment options are available. Aggressive use of antipseudomonal antibiotics is the standard of care for acute pulmonary exacerbations in cystic fibrosis, and providers must take into account specific patient characteristics when making treatment decisions related to antibiotic selection, route and duration of administration, and site of care. PMID- 26857768 TI - The Microbiome in Cystic Fibrosis. AB - Observations from studies during the last decade have changed the conventional view of cystic fibrosis (CF) microbiology, which has traditionally focused on a limited suite of opportunistic bacterial pathogens. It is now appreciated that CF airways typically harbor complex microbial communities, and that changes in the structure and activity of these communities have a bearing on patient clinical condition and lung disease progression. Recent studies of gut microbiota also suggest that disordered bacterial ecology of the CF gastrointestinal tract is associated with pulmonary outcomes. These new insights may alter future clinical management of CF. PMID- 26857770 TI - Nontuberculous Mycobacterial Infections in Cystic Fibrosis. AB - Nontuberculous mycobacteria (NTM) are important emerging cystic fibrosis (CF) pathogens, with estimates of prevalence ranging from 6% to 13%. Diagnosis of NTM disease in patients with CF is challenging, as the infection may remain indolent in some, without evidence of clinical consequence, whereas other patients suffer significant morbidity and mortality. Treatment requires prolonged periods of multiple drugs and varies depending on NTM species, resistance pattern, and extent of disease. The development of a disease-specific approach to the diagnosis and treatment of NTM infection in CF patients is a research priority, as a lifelong strategy is needed for this high-risk population. PMID- 26857771 TI - Nutritional Issues in Cystic Fibrosis. AB - The importance of maintaining adequate nutrition in patients with cystic fibrosis has been well known for the past 3 decades. Achieving normal growth and maintaining optimal nutrition is associated with improved lung function. Comprehensive and consistent nutritional assessments at regular intervals can identify those at risk of nutritional failure and uncover micronutrient deficiencies contributing to malnutrition. Management of malnutrition in cystic fibrosis should follow a stepwise approach to determine the causes and comorbidities and to develop a nutritional plan. Nutritional management is crucial at every stage in a person's life with cystic fibrosis and remains a cornerstone of management. PMID- 26857772 TI - Gastrointestinal Disorders in Cystic Fibrosis. AB - Gastrointestinal (GI) manifestations commonly complicate the care of patients with cystic fibrosis (CF). Despite recent approval of CF transmembrane conductance regulator modulating agents that can improve pulmonary function, GI disorders continue to be relevant and require innovative therapies. This article discusses the most common GI complications of CF, including reflux, pancreatic insufficiency, small bowel intestinal overgrowth, distal intestinal obstruction syndrome, and GI malignancy, with emphasis on clinical presentation and management. PMID- 26857773 TI - Cystic Fibrosis Transitions of Care: Lessons Learned and Future Directions for Cystic Fibrosis. AB - Advances in cystic fibrosis (CF) care transformed the condition from one considered lethal by age 7 into a chronic illness (median lifespan, >40 years). With the growing numbers of adults with CF voicing their preference for care in age appropriate settings, the CF community met the challenge by developing an adult-focused care system modeled on the highly successful pediatric CF centers. Adult CF programs ensure lifelong CF specialty care. Preparation for transfer occurs in a process of "transition." This article reviews progress in transition related care and provides recommendations for research and clinical practice to improve the transition process. PMID- 26857774 TI - Lung Transplantation for Cystic Fibrosis. AB - Lung transplantation is a viable option for many patients with cystic fibrosis (CF) and end-stage lung disease. Criteria for transplant in patients with CF vary widely among transplant centers in terms of acceptable comorbidities; referral to multiple centers may be necessary to maximize patient opportunity for this potentially life-prolonging intervention. Early referral is critical to patient education and modification of risk factors associated with worse outcomes. If transplant evaluation has been completed, patients with CF and respiratory failure requiring mechanical ventilation and extracorporeal membrane oxygenation may remain viable candidates for transplant with outcomes comparable to other individuals with CF. PMID- 26857775 TI - Using Cystic Fibrosis Therapies for Non-Cystic Fibrosis Bronchiectasis. AB - Non-cystic fibrosis bronchiectasis (NCFB) is an increasingly prevalent disease that places a significant burden on patients and health systems globally. Although many of the therapies used to treat NCFB were originally developed as cystic fibrosis (CF) therapies, not all of them have been demonstrated to be efficacious in NCFB and some may even be harmful. This article explores the evidence for which therapeutic strategies used to treat CF have been translated into the care of NCFB. The conclusion is that therapies for adult NCFB cannot be simply extrapolated from CF clinical trials, and in some instances, doing so may actually result in harm. PMID- 26857777 TI - Cystic Fibrosis. PMID- 26857778 TI - In vivo validation of gated myocardial SPECT imaging for quantification of small hearts: comparison with cardiac MRI. AB - BACKGROUND: In patients with small hearts, the Quantitative Gated single-photon emission computed tomography (SPECT) (QGS) program frequently underestimates the left ventricular (LV) end-systolic volume (ESV) and overestimates the ejection fraction (EF). A newly developed cardiac software program, cardioREPO/EXINI heart (cREPO), has been proposed to more accurately quantify small hearts using active shape modeling and a volume-dependent edge correction algorithm for LV delineation. The aim of this study was to validate cREPO in vivo for measuring the LV volumes and EF of both small and non-small hearts, in comparison with values obtained via cardiac MRI (CMR). METHODS: We performed stress (99m)Tc-MIBI SPECT and CMR within a 30-day interval for 44 patients (mean age, 66 years; 27 men). Resting EF, end-diastolic volume (EDV), and ESV with QGS and cREPO were compared with values obtained via CMR. RESULTS: The subjects consisted of 17 small and 27 non-small hearts. CMR yielded EDV, ESV, and EF values of 135 +/- 31 ml (mean +/- SD, range 85-217 ml), 57 +/- 21 ml (27-105 ml), and 60 +/- 6 % (45 70 %), respectively. Compared with CMR, both QGS and cREPO systematically underestimated both EDV and ESV and overestimated EF. The magnitude of the overestimation of EF by QGS, compared with CMR, correlated strongly with the given EF values (r = 0.71, P < 0.0001). In contrast, no significant correlation was seen with cREPO (r = 0.18, P = 0.24). In addition, no significant correlation was found between the magnitude of the underestimation of ESV and heart size with cREPO (r = 0.03, P = 0.83). Thus, cREPO provided a relatively constant 9 % overestimation of EF values relative to CMR, for the studied EF range for both small and non-small hearts. CONCLUSIONS: The use of the new algorithm of cREPO ameliorated exaggerated EF in small hearts but not resolved completely. The program provided a constant 9 % overestimation for both small and non-small hearts, which should be carefully taken into account for clinical assessment of LV function. PMID- 26857776 TI - Acquired Cystic Fibrosis Transmembrane Conductance Regulator Dysfunction in Chronic Bronchitis and Other Diseases of Mucus Clearance. AB - Chronic obstructive pulmonary disease (COPD) is a major public health problem. No therapies alter the natural history of the disease. Chronic bronchitis is perhaps the most clinically troublesome phenotype. Emerging data strongly suggest that cigarette smoke and its components can lead to acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. Findings in vitro, in animal models, and in smokers with and without COPD also show acquired CFTR dysfunction, which is associated with chronic bronchitis. This abnormality is also present in extrapulmonary organs, suggesting that CFTR dysfunction may contribute to smoking-related systemic diseases. PMID- 26857779 TI - Effects of erlotinib therapy on [(11)C]erlotinib uptake in EGFR mutated, advanced NSCLC. AB - BACKGROUND: In non-small cell lung cancer (NSCLC) patients off erlotinib therapy, positron emission tomography (PET) using [(11)C]erlotinib distinguished epidermal growth factor receptor (EGFR) mutations from wild-type EGFR. However, tumor uptake of [(11)C]erlotinib during erlotinib therapy is unknown. Therefore, the aims of this study were to evaluate tumor [(11)C]erlotinib uptake in NSCLC patients both on and off erlotinib therapy, to evaluate the effect of erlotinib therapy on tumor perfusion and its correlation to tumor [(11)C]erlotinib uptake, and also, to investigate simplified uptake parameters using arterial and venous blood samples. METHODS: Ten patients were to be scanned twice with a 1-2-week interval, i.e., on (E+) and off (E-) erlotinib therapy. Each procedure consisted of a low-dose CT scan, a 10-min dynamic [(15)O]H2O PET scan, and a 60-min dynamic [(11)C]erlotinib PET scan with arterial and venous sampling at six time points. In patients(E+), the optimal compartment model was analyzed using Akaike information criterion. In patients(E-), the uptake parameter was the volume of distribution (V T), estimated by using metabolite-corrected plasma input curves based on image-derived input functions and discrete arterial and venous blood samples. Tumor blood flow (TBF) was determined by rate constant of influx (K1) of [(15)O]H2O using the 1T2k model and correlated with V T and K1 values of [(11)C]erlotinib. The investigated simplified parameters were standardized uptake value (SUV) and tumor-to-blood ratio (TBR) at 40-60 min pi interval. RESULTS: Of the 13 patients included, ten were scanned twice. In patients(E+), [(11)C]erlotinib best fitted the 2T4k model with V T. In all patients, tumor V T(E+) was lower than V T(E-) (median V T(E-) = 1.61, range 0.77-3.01; median V T(E+) = 1.17, range 0.53-1.74; P = 0.004). Using [(15)O]H2O, five patients were scanned twice. TBF did not change with erlotinib therapy, TBF showed a positive trend towards correlation with [(11)C]erlotinib K1, but not with V T. TBR40-50 and TBR50-60, using both arterial and venous sampling, correlated with V T(E-) (all r s >0.9, P < 0.001), while SUV did not. In patients off and on therapy, venous TBR underestimated arterial TBR by 26 +/- 12 and 9 +/- 9 %, respectively. CONCLUSIONS: In patients on erlotinib in therapeutic dose, tumor V T decreases with high variability, independent of tumor perfusion. For simplification of [(11)C]erlotinib PET scanning protocols, both arterial and venous TBR 40-60 min post injection can be used; however, arterial and venous TBR values should not be interchanged as venous values underestimate arterial values. TRIAL REGISTRATION: Registered at the Netherlands Trial Registry: NTR3670 . PMID- 26857780 TI - Efficient Enhancement of Electrochemiluminescence from Cadmium Sulfide Quantum Dots by Glucose Oxidase Mimicking Gold Nanoparticles for Highly Sensitive Assay of Methyltransferase Activity. AB - Herein, an original electrochemiluminescence (ECL) method for the detection of DNA methyltransferase (MTase) activity is presented based on the efficient enhanced ECL of CdS quantum dots (QDs) through catalytic generation of coreactant and energy transfer by glucose oxidase mimicking gold nanoparticles (Au NPs). Briefly, a double-stranded DNA (ds-DNA) containing the symmetric sequence of 5' CCGG-3' was bonded to the CdS QDs modified glassy carbon electrode (GCE). After that, the electrode was incubated with M.SssI CpG MTase which catalyzed the methylation of the specific CpG dinucleotides. Subsequently, the electrode was treated with a restriction endonuclease HpaII which could recognize and cut off the 5'-CCGG-3' sequence. Once the CpG site in the 5'-CCGG-3' was methylated, the recognition function of HpaII was blocked, and it could not cut off the ds-DNA. Later, Au NPs were combined with the end of the ds-DNA section which was not cut off and has -SH groups. Therefore, the higher M.SssI MTase activity could lead to more Au NPs immobilized on ds-DNA. Au NPs could not only catalyze the oxidation of glucose with cosubstrate oxygen, producing gluconate and hydrogen peroxide (H2O2) which served as the ECL coreactant of CdS QDs, but also enhanced CdS QDs ECL via energy transfer (ET). Thus, the methylation event corresponding to the MTase activity could be monitored and amplified by this method. Finally, a logarithmic linear correlation between the ECL intensity of CdS QDs and the activity of M.SssI MTase that ranged from 1.0 to 120 U mL(-1) with the detection limit of 0.05 U mL(-1) was obtained. PMID- 26857782 TI - Intrathecal dexmedetomidine as adjuvant to ropivacaine in hysteroscopic surgery: a prospective, randomized control study. AB - BACKGROUND: To compare the effects and side effects of intrathecal ropivacaine supplemented with dexmedetomidine and fentanyl in hysteroscopic surgery under spinal anesthesia. METHODS: Female patients (n = 108) undergoing operative hysteroscopic procedures under spinal anesthesia were randomly allocated to the following groups for subarachnoid drug delivery: R (n = 36) received 7.5 mg ropivacaine; RD (n = 36) received 7.5 mg ropivacaine plus 5 MUg dexmedetomidine; RF (n = 36) received 7.5 mg ropivacaine plus 15 MUg fentanyl. The onset and regression time of sensory and motor blockade, together with the postoperative analgesia and side effects were recorded. RESULTS: There was no significant difference as to sensory and motor onset time between groups. RD had significantly longer sensory and motor blockade time than RF and R. The mean time of sensory regression to the S1 segment was 191.25 +/- 40.24 minutes in RD, 149.86 +/- 37.46 minutes in RF, and 139.44 +/- 38.97 minutes in R (RD vs. R and RD vs. RF, p < 0.001). The regression time of motor blockade to Bromage score 0 was 146.31 +/- 40.72 minutes in RD, 80.28 +/- 41.18 minutes in RF, and 84.94 +/- 26.11 minutes in R (RD vs. R and RD vs. RF, p < 0.001). RD produced similar analgesia effect with RF, (2 hour visual analog scale (VAS) was 0.00 +/- 0.00 and 0.31 +/- 0.79, respectively) better than the R group (1.35 +/- 1.65, p < 0.005). No pruritus occurred in the RD group, while the rate was 36.1% in the RF group. However, the RD group produced milder postsurgical hypotension (RD vs. R and RD vs. RF, p < 0.05). CONCLUSION: Intrathecal dexmedetomidine (5 MUg) produced prolonged motor and sensory blockade and less pruritus compared with fentanyl (15 MUg) in hysteroscopic surgery. PMID- 26857781 TI - Uric acid and high-residual platelet reactivity in patients treated with clopidogrel or ticagrelor. AB - BACKGROUND AND AIM: High residual platelet reactivity (HRPR) is still an important challenge, despite the advent of new potent ADP-antagonists. Therefore it is of extreme importance to identify factors that can influence platelet activation. Serum uric acid (SUA) has been largely addressed in the past as a possible risk factor for coronary artery disease, with a possible association with platelets hyperreactivity. So far no studies have assessed the role of serum uric acid on the response to dual antiplatelet therapy. Therefore, the aim of our study was to evaluate the impact of uric acid levels on platelet function in patients treated with dual antiplatelet therapy (DAPT) with clopidogrel or ticagrelor. METHODS AND RESULTS: We scheduled for platelet function assessment at 30-90 days post-discharge patients treated with DAPT (ASA + clopidogrel or ticagrelor) for an ACS or elective percutaneous coronary intervention (PCI). Platelet function was assessed by whole blood impedance aggregometry (Multiplate((r))-Roche Diagnostics AG), HRPR was considered for ASPI test >862 AU(*)min (for ASA) and ADP test values >=417 AU* min (for ADP-antagonists). RESULTS: We included a total of 493 patients (262 were on ASA and clopidogrel and 231 on ASA and ticagrelor). Patients were divided according to quartiles of serum uric acid levels measured at the time of platelet aggregation assessment (Group 1 <4.6 mg/dL, n = 114; Group 2, 4.7-5.8 mg/dL, n = 133; Group 3, 5.9-6.8 mg/dL, n = 124; Group 4, >6.9, n = 122). Patients with higher uric acid levels were older, more often smokers, with history of hypertension and previous coronary artery bypass surgery and renal failure and were more often on therapy with diuretics at admission. Patients with higher SUA had higher triglycerides and fibrinogen. Uric acid levels did not influence ASPI, COL, TRAP and ADP tests. High residual platelet reactivity (HRPR) was observed in 1.5% of patients treated with ASA, with no difference according to SUA quartiles (p = 0.60), confirmed at multivariate analysis after correction for baseline confounders (adjusted OR[95%CI] = 1.05 [0.44-2.52], p = 0.90). HRPR for ADP-antagonists was observed in 23.6% of patients, with no difference according to SUA quartiles (p = 0.47); this result was confirmed also after correction for baseline confounders (adjusted OR[95%CI] = 1.04 [0.84-1.28], p = 0.73). Moreover, no association was found between HRPR and uric acid levels both among patients treated with clopidogrel (p = 0.35) or ticagrelor (p = 0.74), that was confirmed after correction for baseline confounding factors (adjusted OR[95%CI] = 1.18 [0.90-1.55], p = 0.23) and (adjusted OR[95%CI] = 0.96 [0.63-1.47], p = 0.85). The absence of association between SUA and platelet reactivity was confirmed at linear regression analysis both with clopidogrel (r = 0.03, p = 0.55) or ticagrelor (r = -0.01, p = 0.85). CONCLUSION: This is the first large study showing that in patients receiving DAPT, uric acid levels do not influence response to ticagrelor and clopidogrel or the effectiveness of ASA. PMID- 26857783 TI - Effects of UGT1A1*6, UGT1A1*28, and ABCB1-3435C>T polymorphisms on irinotecan induced toxicity in Chinese cancer patients. AB - OBJECT: The aim of this study was to investigate whether UGT1A1*6/*28 or ABCB1 3435C>T polymorphisms affect irinotecan-induced severe diarrhea and neutropenia in Chinese cancer patients. METHODS: A total of 157 cancer patients was enrolled in this study and the genotypes of UGT1A1*6/*28 and ABCB1-3435C>T polymorphisms were analyzed by PCRSanger sequence. The relationship between UGT1A1*6/*28 and ABCB1-3435C>T polymorphisms and irinotecan induced severe diarrhea and neutropenia were analyzed. RESULTS AND CONCLUSION: UGT1A1*6 and UGT1A1*28 polymorphisms were associated with severe neutropenia (p = 0.025, p = 0.022, respectively) but not diarrhea (p = 0.343, p = 0.185, respectively), and ABCB1- 3435C>T polymorphism was not associated with irinotecan induced severe toxicities (p = 0.457, p = 0.161, respectively). PMID- 26857784 TI - Population pharmacokinetics study of dexmedetomidine in Chinese adult patients during spinal anesthesia. AB - OBJECTIVES: The objectives of this study were to construct a population pharmacokinetics model for dexmedetomidine used in Chinese adult patients with spinal anesthesia and to identify the key factors affecting the pharmacokinetics of dexmedetomidine. METHODS: A total of 34 subjects (elderly group: n = 15; young group: n = 19) undergoing spinal anesthesia received dexmedetomidine with a loading dose of 0.5 MUg*kg(-1) for 10 minutes, followed by a maintenance dose of 0.5 MUg*kg-1*h(-1) for 50 minutes. Blood samples were collected until 10 hours after dosing. Laboratory and respiratory parameters, and dexmedetomidine concentrations were measured. A population pharmacokinetic model for dexmedetomidine was constructed using a nonlinear mixed effects model (NONMEM). RESULTS: Pharmacokinetics of dexmedetomidine can be described by a three compartment model. The respective typical values for clearance (CL), V1, V2, Q2, Q3, and V3 were 0.883 L*min(-1), 17.6 L, 51.5 L, 2.37 L*min(-1), 0.517 L*min(-1), and 44.00 L. Alanine aminotransferase (ALT), age, and body weight were key factors affecting CL, V1, and V2, respectively. CONCLUSIONS: A three-compartment model can be used to describe the pharmacokinetics processing of dexmedetomidine for Chinese adult patients during spinal anesthesia. The population pharmacokinetic of dexmedetomidine was generally in line with results from previous studies. PMID- 26857785 TI - Tooth brushing for a longer and healthier life. PMID- 26857786 TI - The politics of health mobilization in the United States: The promise and pitfalls of "disease constituencies". AB - A critical review of recent literature on U.S. social movements concerned with matters of health and illness prompts reconsideration of the prevailing conception of such movements as necessarily isolated and particularistic. With a focus on disease-constituency-based mobilization-presently the most potent model of efficacious activism to be found in the domain of health and illness in the United States-I argue that such activism may tend in two directions: a specific response to an imminent disease threat, and a bridging of collective action frames and identities that can lead to connections across differences and broader mobilization. Case studies have demonstrated how patient activism has affected the management of illness, attitudes and practices of health professionals, research practices, processes of innovation, state policies, and corporate behavior. Through close analysis of patient group mobilization and its distinctive orientation toward knowledge and expertise, I argue that patient groups in practice may connect with or influence one another or a range of other forms of mobilization in relation to health, and I examine the "linkage mechanisms"-spillover, coalition, and frame amplification-by which this can occur. Rather than imagine a stark opposition between particularistic, single issue health politics, on the one hand, and universalistic efforts to transform the meaning and practice of health and health care in the United States, on the other, I propose closer attention to the potentially Janus-faced character of many health movement organizations and the ways in which they may look either inward or outward. PMID- 26857787 TI - Personalized chemotherapy of lung cancer: What the radiologist should know. AB - Lung cancer is the leading cause of deaths due to cancer in France. More than half of lung cancers are discovered at an advanced-stage. New anticancer treatment strategies (i.e., the so-called personalized or targeted therapy) have recently been introduced and validated for non-small-cell lung cancer (NSCLC), in addition to or in association with standard chemotherapy. Personalized therapy includes tyrosine kinase inhibitors (TKIs), antiangiogenic treatments and immunotherapy. Because these treatments may be responsible for atypical thoracic adverse effects and responses as compared to standard chemotherapy, RECIST 1.1 criteria may be inadequate to evaluate the responses to these agents. The goal of this article was to review personalized treatment strategies for NSCLC, to consider the therapy-specific responses and thoracic complications induced by these new therapeutic agents and finally to discuss future directions for the personalized assessment of tumor response. PMID- 26857788 TI - Quantitative computed tomography in pediatric patients. PMID- 26857789 TI - A Common Rationale for Global Sensitivity Measures and Their Estimation. AB - Measures of sensitivity and uncertainty have become an integral part of risk analysis. Many such measures have a conditional probabilistic structure, for which a straightforward Monte Carlo estimation procedure has a double-loop form. Recently, a more efficient single-loop procedure has been introduced, and consistency of this procedure has been demonstrated separately for particular measures, such as those based on variance, density, and information value. In this work, we give a unified proof of single-loop consistency that applies to any measure satisfying a common rationale. This proof is not only more general but invokes less restrictive assumptions than heretofore in the literature, allowing for the presence of correlations among model inputs and of categorical variables. We examine numerical convergence of such an estimator under a variety of sensitivity measures. We also examine its application to a published medical case study. PMID- 26857790 TI - Training-related changes in muscular and myocardial lymphangiogenesis: how to train the drain? PMID- 26857791 TI - Editorial. PMID- 26857792 TI - Refining the head and neck cancer referral guidelines: a two centre analysis of 4715 referrals. AB - Our aim was to identify the set of referral criteria that will offer optimal diagnostic efficacy in patients suspected to have head and neck cancer (HNC) in the primary care setting. We analysed the referral criteria and outcomes from two tertiary care cancer centres in the United Kingdom. Between 2007 and 2010, 4715 patients were referred via the fast track system with a suspected HNC. The main outcome measures were the parameters of diagnostic efficacy, a multivariate regression model to calculate estimated probability of HNC and the area under the receiver operating characteristic curve (AUROC). We found that the majority of referring symptoms had a positive predictive value higher than the 3% cut-off point stated to be significant for HNC detection in the 2015 NICE recommendations. Nevertheless, our multivariate analysis identified 9 symptoms to be linked with HNC. Of these, only 4 are included in the latest NICE guidelines. The best fit predictive model for this dataset included the following symptoms: hoarseness>3 weeks, dysphagia>3 weeks, odynophagia, unexplained neck mass, oral swelling >3 weeks, oral ulcer >3weeks, prolonged otalgia with normal otoscopy, presence of blood in mouth with concurrent sensation of lump in throat, and presence of otalgia with concurrent lump in throat sensation. Intermittent hoarseness and sensation of lump in throat were negatively associated with HNC. The AUROC demonstrated that our model had a higher predictive value (0.77) compared to those generated using the NICE 2005 (0.69) and 2015 (0.68) referral criteria (p<0.0001). An online risk calculator based on this study is available at http://www.orlhealth.com/risk-calculator.html. This paper presents a significantly refined version of referral guidelines which demonstrate greater diagnostic efficacy than the current NICE guidelines. We recommend that further iterative refinements of referral criteria be considered when referring patients with suspected HNC. PMID- 26857793 TI - Comparison of turbinoplasty surgery efficacy in patients with and without allergic rhinitis. AB - INTRODUCTION: Turbinoplasty is a procedure that aims to reduce the size of the inferior turbinate through exuberant bone removal with high mucosal preservation. The procedure is recommended for patients with or without allergic rhinitis and those showing irreversible hypertrophy of inferior turbinates. OBJECTIVE: To evaluate the efficacy of inferior turbinoplasty for obstructive and non obstructive symptoms in patients with or without allergic rhinitis. METHODS: Prospective study with 57 patients who underwent inferior turbinoplasty. They were evaluated for nasal obstruction, snoring, facial pressure, smell alterations, sneezing, nasal itching and runny nose symptoms, surgery time, and intraoperative bleeding. The last evaluation took place three months after surgery. RESULTS: Thirty-nine patients with allergic rhinitis and 18 without were assessed. Ninety days after surgery, 94.7% of patients showed degrees IV and V of breathing improvement; 89.5% showed moderate or complete improvement in snoring; all patients showed smell improvement (only one showed moderate improvement; all the others had full improvement); 95.5% experienced complete facial pressure improvement; and 89.7% showed moderate to complete improvement in nasal itching and runny nose symptoms, as well as in sneezing. CONCLUSION: The efficacy of inferior turbinoplasty was confirmed not only for obstructive symptoms, but also for non-obstructive symptoms in patients with and without allergic rhinitis. PMID- 26857794 TI - Dietary supplements quality analysis tools from the United States Pharmacopeia. AB - The United States Food and Drug Administration (FDA) issued the dietary supplement (DS) current good manufacturing practice (GMP) regulations in compliance with the mandate from the Dietary Supplements Health and Education Act (DSHEA), with the intention of protecting public health by ensuring the quality of DS. The GMP regulations require manufacturers to establish their own quality specifications for identity, purity, strength, composition, and absence of contaminants. Numerous FDA-conducted GMP inspections found that the private specifications set by these manufacturers are often insufficient to ensure adequate quality of dietary ingredients and DS. Wider use of the public standards developed by the United States Pharmacopeial Convention (USP), in conjunction with GMP compliance, can help ensure quality and consistency of DS as they do for medicines. Public health protection could be enhanced by strengthening the GMP provisions to require conformance with relevant United States Pharmacopeia National Formulary (USP-NF) standards, or in the absence of USP standards, other public compendial standards. Another serious concern is the presence of synthetic drugs and drug analogues in products marketed as DS. Use of the new USP General Chapter Adulteration of Dietary Supplements with Drugs and Drug Analogs <2251> may reduce the exposure of consumers to dangerous drugs disguised as DS. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26857795 TI - Living donor domino liver transplantation using a maple syrup urine disease donor: A case series of three children - The first report from Japan. AB - As the priority of LD-Domino LT is the safety of the first recipient, limitations and technical difficulties in the second recipient often occur. The most technically challenging part of LD-Domino LT is the reconstruction of the vessels. For the reconstruction of HVs, the native HVs were exteriorized as far as possible using a CUSA because longer extensive HVs are essential for facilitating the reconstruction. At the back table, the HVs of the domino graft were sutured together, and the single cuff of the HVs was anastomosed to the IVC by joining the orifices. The HAs, the presence of insufficient length, and multiple vessels in the whole liver rendered the reconstruction more difficult. We determined the dividing sites of the vessels according to the preoperative 3D CT findings obtained in two institutions. This is the first case series using grafts in DLT obtained from LDLT for patients with MSUD between two institutions. In conclusion, LD-Domino LT is a safe and feasible therapeutic option to expand the donor pool by technical refinement in the reconstruction of the second recipient. Further studies with a greater accumulation of patients and a longer follow-up will be necessary to establish LD-Domino LT using an MSUD donor. PMID- 26857796 TI - Modulating NMDA Receptor Function with D-Amino Acid Oxidase Inhibitors: Understanding Functional Activity in PCP-Treated Mouse Model. AB - Deficits in N-methyl-D-aspartate receptor (NMDAR) function are increasingly linked to persistent negative symptoms and cognitive deficits in schizophrenia. Accordingly, clinical studies have been targeting the modulatory site of the NMDA receptor, based on the decreased function of NMDA receptor, to see whether increasing NMDA function can potentially help treat the negative and cognitive deficits seen in the disease. Glycine and D-serine are endogenous ligands to the NMDA modulatory site, but since high doses are needed to affect brain levels, related compounds are being developed, for example glycine transport (GlyT) inhibitors to potentially elevate brain glycine or targeting enzymes, such as D amino acid oxidase (DAAO) to slow the breakdown and increase the brain level of D serine. In the present study we further evaluated the effect of DAAO inhibitors 5 chloro-benzo[d]isoxazol-3-ol (CBIO) and sodium benzoate (NaB) in a phencyclidine (PCP) rodent mouse model to see if the inhibitors affect PCP-induced locomotor activity, alter brain D-serine level, and thereby potentially enhance D-serine responses. D-Serine dose-dependently reduced the PCP-induced locomotor activity at doses above 1000 mg/kg. Acute CBIO (30 mg/kg) did not affect PCP-induced locomotor activity, but appeared to reduce locomotor activity when given with D serine (600 mg/kg); a dose that by itself did not have an effect. However, the effect was also present when the vehicle (Trappsol((r))) was tested with D serine, suggesting that the reduction in locomotor activity was not related to DAAO inhibition, but possibly reflected enhanced bioavailability of D-serine across the blood brain barrier related to the vehicle. With this acute dose of CBIO, D-serine level in brain and plasma were not increased. Another weaker DAAO inhibitor NaB (400 mg/kg), and NaB plus D-serine also significantly reduced PCP induced locomotor activity, but without affecting plasma or brain D-serine level, arguing against a DAAO-mediated effect. However, NaB reduced plasma L-serine and based on reports that NaB also elevates various plasma metabolites, for example aminoisobutyric acid (AIB), a potential effect via the System A amino acid carrier may be involved in the regulation of synaptic glycine level to modulate NMDAR function needs to be investigated. Acute ascorbic acid (300 mg/kg) also inhibited PCP-induced locomotor activity, which was further attenuated in the presence of D-serine (600 mg/kg). Ascorbic acid may have an action at the dopamine membrane carrier and/or altering redox mechanisms that modulate NMDARs, but this needs to be further investigated. The findings support an effect of D serine on PCP-induced hyperactivity. They also offer suggestions on an interaction of NaB via an unknown mechanism, other than DAAO inhibition, perhaps through metabolomic changes, and find unexpected synergy between D-serine and ascorbic acid that supports combined NMDA glycine- and redox-site intervention. Although mechanisms of these specific agents need to be determined, overall it supports continued glutamatergic drug development. PMID- 26857797 TI - Characteristic fingerprinting based on macamides for discrimination of maca (Lepidium meyenii) by LC/MS/MS and multivariate statistical analysis. AB - BACKGROUND: Macamides with a benzylalkylamide nucleus are characteristic and major bioactive compounds in the functional food maca (Lepidium meyenii Walp). The aim of this study was to explore variations in macamide content among maca from China and Peru. Twenty-seven batches of maca hypocotyls with different phenotypes, sampled from different geographical origins, were extracted and profiled by liquid chromatography with ultraviolet detection/tandem mass spectrometry (LC-UV/MS/MS). RESULTS: Twelve macamides were identified by MS operated in multiple scanning modes. Similarity analysis showed that maca samples differed significantly in their macamide fingerprinting. Partial least squares discriminant analysis (PLS-DA) was used to differentiate samples according to their geographical origin and to identify the most relevant variables in the classification model. The prediction accuracy for raw maca was 91% and five macamides were selected and considered as chemical markers for sample classification. CONCLUSION: When combined with a PLS-DA model, characteristic fingerprinting based on macamides could be recommended for labelling for the authentication of maca from different geographical origins. The results provided potential evidence for the relationships between environmental or other factors and distribution of macamides. (c) 2016 Society of Chemical Industry. PMID- 26857799 TI - Nursing diagnoses, outcomes and interventions as measures of patient complexity and nursing care requirement in Intensive Care Unit. AB - AIMS: To describe the nursing diagnoses, outcomes and interventions for patients admitted to intensive care units and to assess their possible relation with classical outcomes like length of stay and mortality. BACKGROUND: The analysis of nursing diagnosis frequencies may help to estimate the patients' complexity and the need for nursing interventions and can predict hospital outcomes. Nonetheless, few studies were conducted on critical patients. DESIGN: Prospective cohort observational study. METHODS: Between 15 July-31 October 2013 we collected the above-described nursing parameters of 100 subjects throughout their stay in intensive care. We classified the parameters according to established taxonomies. The independent association between the number of nursing diagnoses and length of stay/mortality was investigated with multiple regressions. RESULTS: We found an average of 19 diagnoses, 24 outcomes and 60 interventions per patient. Most frequently, the plans of care involved support for self-care deficits or interrupted family processes. They also included strategies to prevent infection, disuse syndrome and impairment of skin integrity. Nineteen nursing diagnoses were significantly related with mortality or length of stay in bivariate analyses. In regression models, the number of such diagnoses explained 29.7% of the variance in length of stay and was an independent predictor of mortality. CONCLUSION: In critically ill patients, the analysis of nursing diagnoses, outcomes and interventions confirmed an intense activity in response to a broad spectrum of patient needs. The number of nursing diagnoses allowed to predict patient outcomes. PMID- 26857800 TI - Massive malignant pleural effusion due to lung adenocarcinoma in 13-year-old boy. AB - A 13-year-old boy with no risk factors for lung cancer presented with a massive left-sided pleural effusion and a mediastinal shift on chest radiography and computed tomography. A chest tube drained bloody pleural fluid with an exudative pattern. A pleural biopsy and wedge biopsy of the left lower lobe revealed mucinous adenocarcinoma in the left lower lobe wedge biopsy and metastatic adenocarcinoma in the pleural biopsy. The patient is currently undergoing chemotherapy. Radiotherapy is planned after shrinkage of the tumor. Adenocarcinoma of the lung is very rarely seen in teenagers or children, especially in the absence of risk factors. PMID- 26857802 TI - Temperature Dependence of NMR Parameters Calculated from Path Integral Molecular Dynamics Simulations. AB - The influence of temperature on NMR chemical shifts and quadrupolar couplings in model molecular organic solids is explored using path integral molecular dynamics (PIMD) and density functional theory (DFT) calculations of shielding and electric field gradient (EFG) tensors. An approach based on convoluting calculated shielding or EFG tensor components with probability distributions of selected bond distances and valence angles obtained from DFT-PIMD simulations at several temperatures is used to calculate the temperature effects. The probability distributions obtained from the quantum PIMD simulations, which includes nuclear quantum effects, are significantly broader and less temperature dependent than those obtained with conventional DFT molecular dynamics or with 1D scans through the potential energy surface. Predicted NMR observables for the model systems were in excellent agreement with experimental data. PMID- 26857801 TI - [Septic shock in paediatrics: Less is more]. PMID- 26857798 TI - Procoagulant microparticles promote coagulation in a factor XI-dependent manner in human endotoxemia. AB - Essentials The procoagulant effects of microparticles (MPs) on coagulation in endotoxemia are not known. MPs from endotoxemia volunteers were evaluated for procoagulant activity in a plasma milieu. MPs from endotoxemia volunteers shortened clotting times and enhanced thrombin generation. MP procoagulant effects were mediated in a factor XI-dependent manner. SUMMARY: Background Human endotoxemia is characterized by acute inflammation and activation of coagulation, as well as increased numbers of circulating microparticles (MPs). Whether these MPs directly promote coagulation and through which pathway their actions are mediated, however, has not been fully explored. Objectives In this study, we aimed to further characterize endotoxin-induced MPs and their procoagulant properties using several approaches. Methods Enumeration and characterization of MPs were performed using a new-generation flow cytometer. Relative contributions of the extrinsic and intrinsic pathways in MP-mediated procoagulant activity were assessed using plasmas deficient in factor (F) VII or FXI or with blocking antibodies to tissue factor (TF) or FXIa. Results Total MPs and platelet MPs were significantly elevated in plasma at 6 h after infusion of endotoxin in healthy human subjects. MPs isolated from plasma following endotoxin infusion also demonstrated increased TF activity in a reconstituted buffer system. When added to recalcified platelet-poor plasma, these MPs also promoted coagulation, as judged by a decreased clotting time with shortening of the lag time and time to peak thrombin using calibrated automated thrombography (CAT). However, the use of FVII-deficient plasma or blocking antibody to TF did not inhibit these procoagulant effects. In contrast, plasma clotting time was prolonged in FXI deficient plasma and a blocking antibody to FXIa inhibited all MP-mediated parameters in the CAT assay. Conclusions The initiation of coagulation by cellular TF in endotoxemia is in contrast to (and presumably complemented by) the intrinsic pathway-mediated procoagulant effects of circulating MPs. PMID- 26857803 TI - Solid-state NMR structures of integral membrane proteins. AB - Solid-state NMR is unique for its ability to obtain three-dimensional structures and to measure atomic-resolution structural and dynamic information for membrane proteins in native lipid bilayers. An increasing number and complexity of integral membrane protein structures have been determined by solid-state NMR using two main methods. Oriented sample solid-state NMR uses macroscopically aligned lipid bilayers to obtain orientational restraints that define secondary structure and global fold of embedded peptides and proteins and their orientation and topology in lipid bilayers. Magic angle spinning (MAS) solid-state NMR uses unoriented rapidly spinning samples to obtain distance and torsion angle restraints that define tertiary structure and helix packing arrangements. Details of all current protein structures are described, highlighting developments in experimental strategy and other technological advancements. Some structures originate from combining solid- and solution-state NMR information and some have used solid-state NMR to refine X-ray crystal structures. Solid-state NMR has also validated the structures of proteins determined in different membrane mimetics by solution-state NMR and X-ray crystallography and is therefore complementary to other structural biology techniques. By continuing efforts in identifying membrane protein targets and developing expression, isotope labelling and sample preparation strategies, probe technology, NMR experiments, calculation and modelling methods and combination with other techniques, it should be feasible to determine the structures of many more membrane proteins of biological and biomedical importance using solid-state NMR. This will provide three-dimensional structures and atomic-resolution structural information for characterising ligand and drug interactions, dynamics and molecular mechanisms of membrane proteins under physiological lipid bilayer conditions. PMID- 26857805 TI - Association of Serum hs-CRP Levels With the Presence of Obesity, Diabetes Mellitus, and Other Cardiovascular Risk Factors. AB - BACKGROUND: Diabetes mellitus remains one of the major health problems of the 21st century and is associated with comorbidities including obesity and metabolic abnormalities. The study was conducted to evaluate serum high-sensitivity C reactive protein (hs-CRP) levels, as a marker of inflammation, in a large sample of Iranian population without a history of cardiovascular or inflammatory disease and cancer, and to relate this to fasting blood glucose (FBG) and the presence of diabetes mellitus. METHODS: The study consisted of 7,762 subjects divided into four groups-nonobese/nondiabetic, obese/nondiabetic, nonobese/diabetic and obese/diabetic-based on the BMI classification and their FBG. Anthropometric characteristics were measured and blood was collected for the evaluation of fasted lipid profile, FBG and serum hs-CRP levels. RESULTS: Several clinical and biochemical characteristics were significantly different among the four groups: FBG, P < 0.001; total cholesterol (TC), P < 0.001; and triglyceride (TG), P < 0.001. The subjects with a serum hs-CRP >3 mg/dl had higher TC (P < 0.001), low density lipoprotein cholesterol (LDL-C, P < 0.001), TG (P < 0.001), fat percentage (P < 0.001), and systolic and diastolic blood pressure (P < 0.001) compared with subjects with a serum hs-CRP <3 mg/dl. Multivariate analysis showed FBG, LDL-C, and waist circumference (WC) associated with increased serum hs-CRP levels (P < 0.001). CONCLUSIONS: FBG, LDL-C, WC and gender are independently associated with serum hs-CRP concentrations. PMID- 26857804 TI - Exposure to Alcohol Use in Motion Pictures and Teen Drinking in Latin America. AB - BACKGROUND: Our objective was to assess whether exposure to alcohol use in films (AUF) is associated with alcohol use susceptibility, current alcohol use, and binge drinking in adolescents from 2 Latin American countries. METHODS: We performed a cross-sectional study with 13,295 middle school students from public and private schools in Mexico and Argentina. Exposure to alcohol use in over 400 contemporary top box office films in each country was estimated using previously validated methods. Outcome measures included current drinking (i.e., any drink in the last 30 days), ever binge drinking (i.e., more than 4 or 5 drinks in a row for females and males, respectively) and, among never drinkers, alcohol susceptibility (i.e., might drink in the next year or accept a drink from a friend). Multivariate models were adjusted for age, sex, parental education, peer drinking, sensation seeking, parenting style, and media access. RESULTS: Mean age was 12.5 years (SD = 0.7), and the prevalence of alcohol consumption and binge drinking was 19.8 and 10.9%, respectively. Mean exposure to alcohol from the film sample was about 7 hours in both countries. Adjusted models indicated independent dose-response associations between higher levels of exposure to AUF and all outcomes; the adjusted odds ratios (aORs) comparing quartiles 4 and 1, 1.99 (95% confidence interval [CI] 1.73 to 2.30) for current drinking, aOR 1.68 (CI 1.39 to 2.02) for binge drinking, and aOR 1.80 (1.52 to 2.12) for alcohol susceptibility. Compared to Mexican adolescents, Argentine adolescents were significantly more likely to have engaged in binge drinking (aOR 1.40, 95% CI 1.12 to 1.76) and, among never drinkers, were more susceptible to try drinking (aOR 1.40, 95% CI 1.20 to 1.64). CONCLUSIONS: Higher levels of exposure to AUF were associated with higher likelihood of alcohol use, binge drinking, and alcohol susceptibility in Latin American adolescents. PMID- 26857807 TI - Dried Blood-Spot Thyroglobulin Measurement: Field-Friendly and Ready for Field Testing. PMID- 26857806 TI - Virulence markers of opportunistic black yeast in Exophiala. AB - The black yeast genus Exophiala is known to cause a wide variety of diseases in severely ill individuals but can also affect immunocompetent individuals. Virulence markers and other physiological parameters were tested in eight clinical and 218 environmental strains, with a specific focus on human-dominated habitats for the latter. Urease and catalase were consistently present in all samples; four strains expressed proteinase and three strains expressed DNase, whereas none of the strains showed phospholipase, haemolysis, or co-haemolysis activities. Biofilm formation was identified in 30 (13.8%) of the environmental isolates, particularly in strains from dishwashers, and was noted in only two (25%) of the clinical strains. These results indicate that virulence factors are inconsistently present in the investigated Exophiala species, suggesting opportunism rather than pathogenicity. PMID- 26857808 TI - Transactions in Suffering: Mothers, Daughters, and Chronic Disease Comorbidities in New Delhi, India. AB - The biomedical definition of comorbidity belies the complexity of its lived experience. This article draws on case studies of women with diabetes and various comorbidities in New Delhi, India, to explore intergenerational transactions surrounding suffering in contexts of comorbidity. The analysis synthesizes sociological theories of chronic disease work, psychological theories of caregiver burnout, and anthropological approaches to suffering and legitimacy to explore how, when, and by whom women's comorbid sources of suffering become routinized in everyday life. The analysis demonstrates, first, that comorbid suffering is not simply a matter of the addition of a second source of suffering to an existing one; rather, it comprises complex interactions between suffering, disability, family dynamics, and quality of life. Second, it illustrates several social routes through which comorbid suffering can fade into the background of everyday life, even when it is severe. Close attention to how suffering works in cases of comorbidity will be important as comorbid conditions become increasingly commonplace around the world. PMID- 26857809 TI - A review of induced pluripotent stem cell, direct conversion by trans differentiation, direct reprogramming and oligodendrocyte differentiation. AB - Rapid progress in the field of stem cell therapy and cellular reprogramming provides convincing evidence of its feasibility in treating a wide range of pathologies through autologous cell replacement therapy. This review article describes in detail on three widely used approaches of somatic cell reprogramming: induced pluripotent stem cells, direct conversion and direct reprogramming, in the context of demyelination in the CNS. The potential limitations of each reprogramming technique are reviewed along with their distinct molecular approach to reprogramming. This is followed by an analysis on the scopes and challenges of its translational applications in deriving oligodendrocyte progenitor cells and oligodendrocytes for cell replacement treatment of demyelinating conditions in the CNS. PMID- 26857810 TI - The fungal-specific transcription factor Vdpf influences conidia production, melanized microsclerotia formation and pathogenicity in Verticillium dahliae. AB - Verticillium dahliae is a soil-borne, hemibiotrophic phytopathogenic fungus that causes wilting in crop plants. Here, we constructed a random insertional mutant library using Agrobacterium tumefaciens-mediated transformation to study the pathogenicity and regulatory mechanisms of V. dahliae. The fungal-specific transcription factor-encoding gene Vdpf was shown to be associated with vegetative growth and virulence, with the highest transcript expression occurring during conidia formation in the V991 strain. The deletion mutants (DeltaVdpf) and insertion mutants (IMDeltaVdpf) produced fewer conidia than did the wild-type (WT) fungi, which contributed to the reduced virulence. Unlike the WT, the complemented strains and IMDeltaVdpf, DeltaVdpf formed swollen, thick-walled and hyaline mycelium rather than melanized microsclerotia. The DeltaVdpf mutants were melanin deficient, with undetectable expression of melanin biosynthesis-related genes (Brn1, Brn2 and Scd1). The melanin deficiency was related to cyclic adenosine monophosphate (cAMP) and the G-protein-coupled signalling pathways in this study. Similar to the WT and complemented strains, the DeltaVdpf and IMDeltaVdpf mutants could also successfully penetrate into cotton and tobacco roots, but displayed reduced virulence because of lower biomass in the plant roots and significantly reduced expression of pathogenicity-related genes in V. dahliae. In conclusion, these results provide insights into the role of Vdpf in melanized microsclerotia formation, conidia production and pathogenicity. PMID- 26857811 TI - Differences in polysubstance use patterns and drug-related outcomes between people who inject drugs receiving and not receiving opioid substitution therapies. AB - AIMS: To test if polysubstance use profiles and drug-related outcomes differ between those receiving and not receiving opioid substitution therapies (OST) among people who inject drugs (PWID). DESIGN: An annual cross-sectional, sentinel sample of PWID across Australia. SETTING: Data came from 3 years (2011-13) of the Illicit Drug Reporting System (IDRS). PARTICIPANTS: A total of 2673 participants who injected drugs from the combined national IDRS samples of 2011 (n = 868), 2012 (n = 922) and 2013 (n = 883). MEASUREMENTS: Latent class analysis (LCA) was used to summarize participants' self-reported use of 18 types of substances, with the resulting polysubstance use profiles then associated with participant experience of a number of drug-related outcomes. FINDINGS: Polysubstance use profiles exhibiting a broad range of substance use were generally at increased risk of negative drug-related outcomes, whether or not participants were receiving OST, including thrombosis among OST receivers [odds ratio (OR) = 2.13, 95% confidence intervals (CI) = 1.09-4.17], injecting with used needles among OST receivers and non-receivers, respectively (OR = 2.78, 95% CI = 1.50-5.13; OR = 2.15, 95% CI = 1.34-3.45) and violent criminal offences among OST receivers and non-receivers, respectively (OR =2.30, 95% CI = 1.16-4.58; OR = 1.87, 95% CI = 1.14-3.07). An important exception was non-fatal overdose which was related specifically to a class of PWID who were not receiving OST and used morphine frequently (OR = 1.83, 95% CI = 1.06-3.17) CONCLUSION: Regardless of opioid substitution therapies usage, people who inject drugs who use a broad-range of substances experience greater levels of injecting-related injuries and poorer health outcomes and are more likely to engage in criminal activity than other groups of people who inject drugs. PMID- 26857812 TI - Oral medication delivery in impaired swallowing: thickening liquid medications for safe swallowing alters dissolution characteristics. AB - Acetaminophen (paracetamol) is available in a wide range of oral formulations designed to meet the needs of the population across the age-spectrum, but for people with impaired swallowing, i.e. dysphagia, both solid and liquid medications can be difficult to swallow without modification. The effect of a commercial polysaccharide thickener, designed to be added to fluids to promote safe swallowing by dysphagic patients, on rheology and acetaminophen dissolution was tested using crushed immediate-release tablets in water, effervescent tablets in water, elixir and suspension. The inclusion of the thickener, comprised of xanthan gum and maltodextrin, had a considerable impact on dissolution; acetaminophen release from modified medications reached 12-50% in 30 min, which did not reflect the pharmacopeia specification for immediate release preparations. Flow curves reflect the high zero-shear viscosity and the apparent yield stress of the thickened products. The weak gel nature, in combination with high G' values compared to G'' (viscoelasticity) and high apparent yield stress, impact drug release. The restriction on drug release from these formulations is not influenced by the theoretical state of the drug (dissolved or dispersed), and the approach typically used in clinical practice (mixing crushed tablets into pre prepared thickened fluid) cannot be improved by altering the order of incorporation or mixing method. PMID- 26857813 TI - Critical review of methods for risk ranking of food-related hazards, based on risks for human health. AB - This study aimed to critically review methods for ranking risks related to food safety and dietary hazards on the basis of their anticipated human health impacts. A literature review was performed to identify and characterize methods for risk ranking from the fields of food, environmental science and socio economic sciences. The review used a predefined search protocol, and covered the bibliographic databases Scopus, CAB Abstracts, Web of Sciences, and PubMed over the period 1993-2013. All references deemed relevant, on the basis of predefined evaluation criteria, were included in the review, and the risk ranking method characterized. The methods were then clustered-based on their characteristics into eleven method categories. These categories included: risk assessment, comparative risk assessment, risk ratio method, scoring method, cost of illness, health adjusted life years (HALY), multi-criteria decision analysis, risk matrix, flow charts/decision trees, stated preference techniques and expert synthesis. Method categories were described by their characteristics, weaknesses and strengths, data resources, and fields of applications. It was concluded there is no single best method for risk ranking. The method to be used should be selected on the basis of risk manager/assessor requirements, data availability, and the characteristics of the method. Recommendations for future use and application are provided. PMID- 26857815 TI - The integrin-collagen connection--a glue for tissue repair? AB - The alpha1beta1, alpha2beta1, alpha10beta1 and alpha11beta1 integrins constitute a subset of the integrin family with affinity for GFOGER-like sequences in collagens. Integrins alpha1beta1 and alpha2beta1 were originally identified on a subset of activated T-cells, and have since been found to be expressed on a number of cell types including platelets (alpha2beta1), vascular cells (alpha1beta1, alpha2beta1), epithelial cells (alpha1beta1, alpha2beta1) and fibroblasts (alpha1beta1, alpha2beta1). Integrin alpha10beta1 shows a distribution that is restricted to mesenchymal stem cells and chondrocytes, whereas integrin alpha11beta1 appears restricted to mesenchymal stem cells and subsets of fibroblasts. The bulk of the current literature suggests that collagen binding integrins only have a limited role in adult connective tissue homeostasis, partly due to a limited availability of cell-binding sites in the mature fibrillar collagen matrices. However, some recent data suggest that, instead, they are more crucial for dynamic connective tissue remodeling events- such as wound healing--where they might act specifically to remodel and restore the tissue architecture. This Commentary discusses the recent development in the field of collagen-binding integrins, their roles in physiological and pathological settings with special emphasis on wound healing, fibrosis and tumor stroma interactions, and include a discussion of the most recently identified newcomers to this subfamily--integrins alpha10beta1 and alpha11beta1. PMID- 26857816 TI - Soluble adenylyl cyclase mediates hydrogen peroxide-induced changes in epithelial barrier function. AB - BACKGROUND: Elevated H2O2 levels are associated with inflammatory diseases and H2O2 exposure is known to disrupt epithelial barrier function, leading to increased permeability and decreased electrical resistance. In normal human bronchial epithelial (NHBE) cells, fully differentiated at the air liquid interface (ALI), H2O2 activates an autocrine prostaglandin pathway that stimulates transmembrane adenylyl cyclase (tmAC) as well as soluble adenylyl cyclase (sAC), but the role of this autocrine pathway in H2O2-mediated barrier disruption is not entirely clear. METHODS: To further characterize the mechanism of H2O2-induced barrier disruption, NHBE cultures were treated with H2O2 and evaluated for changes in transepithelial resistance and mannitol permeability using agonist and inhibitors to dissect the pathway. RESULTS: A short (<10 min) H2O2 treatment was sufficient to induce resistance and permeability changes that occurred 40 min to 1 h later and the changes were partially sensitive to EP1 but not EP4 receptor antagonists. EP1 receptors were localized to the apical compartment of NHBE. Resistance and permeability changes were sensitive to inhibition of sAC but not tmAC and were partially blocked by PKA inhibition. Pretreatment with a PLC inhibitor or an IP3 receptor antagonist reduced changes in resistance and permeability suggesting activation of sAC occurred through increased intracellular calcium. CONCLUSION: The data support an important role for prostaglandin activation of sAC and PKA in H2O2-induced barrier disruption. PMID- 26857814 TI - A new role for cofilin in retinal neovascularization. AB - Pak1 plays an important role in several cellular processes, including cell migration, but its role in pathological angiogenesis is not known. Here, we have determined its role in pathological retinal angiogenesis using an oxygen-induced retinopathy (OIR) model. VEGFA induced phosphorylation of Pak1 and its effector cofilin in a manner that was dependent on time as well as p38MAPKbeta (also known as MAPK11) in human retinal microvascular endothelial cells (HRMVECs). Depletion of the levels of any of these molecules inhibited VEGFA-induced HRMVEC F-actin stress fiber formation, migration, proliferation, sprouting and tube formation. In accordance with these observations, hypoxia induced Pak1 and cofilin phosphorylation with p38MAPKbeta being downstream to Pak1 and upstream to cofilin in mouse retina. Furthermore, Pak1 deficiency abolished hypoxia-induced p38MAPKbeta and cofilin phosphorylation and abrogated retinal endothelial cell proliferation, tip cell formation and neovascularization. In addition, small interfering RNA (siRNA)-mediated downregulation of p38MAPKbeta or cofilin levels in the wild-type mouse retina also diminished endothelial cell proliferation, tip cell formation and neovascularization. Taken together, these observations suggest that, although the p38MAPKbeta-Pak1-cofilin axis is required for HRMVEC migration, proliferation, sprouting and tubulogenesis, Pak1-p38MAPKbeta-cofilin signaling is also essential for hypoxia-induced mouse retinal endothelial cell proliferation, tip cell formation and neovascularization. PMID- 26857817 TI - A 3D alcoholic liver disease model on a chip. AB - Alcohol is one of the main causes of liver diseases, and the development of alcoholic liver disease (ALD) treatment methods has been one of the hottest issues. For this purpose, development of in vitro models mimicking the in vivo physiology is one of the critical requirements, and they help to determine the disease mechanisms and to discover the treatment method. Herein, a three dimensional (3D) ALD model was developed and its superior features in mimicking the in vivo condition were demonstrated. A spheroid-based microfluidic chip was employed for the development of the 3D in vitro model of ALD progression. We co cultured rat primary hepatocytes and hepatic stellate cells (HSCs) in a fluidic chip to investigate the role of HSCs in the recovery of liver with ALD. An interstitial level of flow derived by an osmotic pump was applied to the chip to provide in vivo mimicking of fluid activity. Using this in vitro tool, we were able to observe structural changes and decreased hepatic functions with the increase in ethanol concentration. The recovery process of liver injured by alcohol was observed by providing fresh culture medium to the damaged 3D liver tissue for few days. A reversibly- and irreversibly-injured ALD model was established. The proposed model can not only be used for the research of alcoholic disease mechanism, but also has the potential for use in studies of hepatotoxicity and drug screening applications. PMID- 26857818 TI - FDG PET/CT as a prognostic biomarker in the era of molecular-targeting therapies: max SUVmax predicts survival of patients with advanced renal cell carcinoma. AB - BACKGROUND: Various molecular-targeting therapies have become available for the treatment of advanced renal cell carcinoma (RCC). Accurate prognostication is desirable for choosing the appropriate treatment for individual patients. (18)F-2 fluoro-2-deoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) is a non-invasive tool for evaluating glucose accumulation, which can be an index of biological characteristics of cancer. We prospectively evaluated FDG PET/CT as a prognostic indicator in patients with advanced RCC. METHODS: A total of 101 patients slated for different systematic therapies for advanced RCC were enrolled between 2008 and 2014. A total of 61 patients had recurrent RCC (58 metastatic and 3 regional) and 40 patients had stage IV RCC (36 metastatic and 4 locoregional). Sixteen patients had not undergone nephrectomy. Pre-treatment FDG PET/CT was performed, and the max SUVmax (the highest SUV measurement in each patient) was recorded. The max SUVmax was compared with different clinical risk factors as prognostic indicators. The median observation period was 18 months (range 1-70 months). RESULTS: The max SUVmax of the 101 subjects ranged from undetectable to 23.0 (median 6.9). Patients with high max SUVmax had a poor prognosis. Multivariate analysis with standard risk factors revealed that max SUVmax was an independent predictor of survival (p < 0.001; hazard ratio 1.265; 95% confidence interval 1.159-1.380). A cutoff of 8.8 for max SUVmax advocated in our previous report was highly significant (p < 0.0001). When we subclassified the max SUVmax values, the median overall survival of subjects with max SUVmax < 7.0 was 41.9 months. That of subjects with max SUVmax between 7.0 and 12.0 was 20.6 months. That of subjects with max SUVmax >= 12.0 was 4.2 months. The differences were statistically significant. CONCLUSIONS: Pretreatment max SUVmax assessed by FDG PET/CT is a useful prognostic marker for patients with advanced RCC, providing helpful information for clinical decision making. PMID- 26857819 TI - Evaluation of the utricular and saccular function using oVEMPs and cVEMPs in BPPV patients. AB - BACKGROUND: It is well-known that ocular vestibular evoked myogenic potentials (oVEMPs) predominantly reflect utricular function whilst cervical vestibular evoked myogenic potentials (cVEMPs) reflect saccular function. To date, there are no published reports on the systemic evaluation of utricular and saccular function in benign paroxysmal positional vertigo (BPPV), nor are there any reports on the differences in VEMPs between patients with recurrent and non recurrent BPPV. The aim of this study was to evaluate the difference in cervical and ocular (c/o)VEMPs between patients with BPPV and normal controls, as well as between patients with recurrent and non-recurrent BPPV. METHODS: Thirty patients with posterior canal BPPV and 30 healthy subjects (as normal controls) were prospectively enrolled. cVEMP and oVEMP testing using 500 Hz tone-burst stimuli were performed on all. VEMP tests were repeated 3 times on each subject to ensure reliability and reproducibility of responses. VEMPs were defined as present or absent. Abnormal VEMP was defined by lack of VEMP response. RESULTS: In the control group, abnormal cVEMPs responses were detected in 6.67% and abnormal oVEMPs responses were detected in 3.34%. In BPPV patients (10 with recurrent BPPV, 20 with non-recurrent BPPV), abnormal cVEMPs responses were detected in 30% and abnormal oVEMPs responses were detected in 56.7%. More patients with BPPV showed abnormal responses in c/oVEMPs as compared to the control group (p < 0.05). oVEMPs was more often abnormal as compared to cVEMPs in BPPV patients (p < 0.05). There was no statistical difference between abnormal cVEMP responses in non-recurrent BPPV patients (25%) and recurrent BPPV patients (40%) (p > 0.05). Differences in abnormal oVEMP responses (non-recurrent BPPV, 40%; recurrent BPPV, 90%) were significant (p < 0.05). CONCLUSION: An increased occurrence of abnormal c/oVEMP recordings appeared in BPPV patients, possibly as a result of degeneration of the otolith macula. oVEMPs were more often abnormal in BPPV patients as compared to cVEMPs, suggesting that utricular dysfunction may be more common than saccular dysfunction. Furthermore, oVEMP abnormalities in the recurrent BPPV group were significantly higher than those in the non-recurrent BPPV group. Assessment of c/oVEMPs in BPPV patients may therefore be of prognostic value in predicting likelihood of BPPV recurrence. PMID- 26857820 TI - European Headache Federation consensus on technical investigation for primary headache disorders. AB - The diagnosis of primary headache disorders is clinical and based on the diagnostic criteria of the International Headache Society (ICHD-3-beta). However several brain conditions may mimic primary headache disorders and laboratory investigation may be needed. This necessity occurs when the treating physician doubts for the primary origin of headache. Features that represent a warning for a possible underlying disorder causing the headache are new onset headache, change in previously stable headache pattern, headache that abruptly reaches the peak level, headache that changes with posture, headache awakening the patient, or precipitated by physical activity or Valsalva manoeuvre, first onset of headache >=50 years of age, neurological symptoms or signs, trauma, fever, seizures, history of malignancy, history of HIV or active infections, and prior history of stroke or intracranial bleeding. All national headache societies and the European Headache Alliance invited to review and comment the consensus before the final draft. The consensus recommends brain MRI for the case of migraine with aura that persists on one side or in brainstem aura. Persistent aura without infarction and migrainous infarction require brain MRI, MRA and MRV. Brain MRI with detailed study of the pituitary area and cavernous sinus, is recommended for all TACs. For primary cough headache, exercise headache, headache associated with sexual activity, thunderclap headache and hypnic headache apart from brain MRI additional tests may be required. Because there is little and no good evidence the committee constructed a consensus based on the opinion of experts, and should be treated as imperfect. PMID- 26857821 TI - Impact of the radiographic examination on diagnosis and treatment decision of caries lesions in primary teeth--the Caries Detection in Children (CARDEC-01) trial: study protocol for a randomized controlled trial. AB - BACKGROUND: Although most clinical guidelines throughout the world indicate that clinicians take two bitewings for detecting caries lesions in primary molars of all children, evidence for this recommendation is essentially based on cross sectional studies performed in laboratory settings or using convenience samples. The benefits and impact of performing radiographs on diagnosis and treatment decision of caries lesions in primary teeth, mainly considering relevant outcomes for patients, have not been evaluated yet. Thus, the aim of this randomized clinical trial will be to evaluate the impact of performing radiographic examination adjunct to the visual inspection for detecting and making treatment decision regarding caries lesions in primary teeth compared with visual inspection performed alone. We will consider different outcomes related to children's health and welfare. METHODS/DESIGN: To reach this objective, 250 children ages 3 to 6 years who sought dental treatment in our dental school will be randomly allocated in two groups according to the diagnostic strategy used for caries detection: visual inspection performed alone or visual inspection associated to radiographic examination. Two trained and calibrated examiners will carry out the examinations and elaborate the treatment decision plan. Then, children will be treated and followed up for 2 years, with evaluations after 12 and 24 months after the inclusion of children in the study. Children will also return after 6 and 18 months to reinforce the preventive orientations. Primary outcome will be the number of dental surfaces in need of dental treatment at the follow-up. Secondary outcomes will be the components of the primary outcome separately, as well as, proportion of false-positive results, the oral health related quality of life, cost-efficacy, cost-adjusted life years, and number of new lesions in the first permanent molars. DISCUSSION: Our working hypothesis is that radiographic examination would actually exert little influence on patient centered outcomes, and visual inspection would be enough as diagnostic strategy for caries detection in primary teeth. TRIAL REGISTRATION: NCT02078453. Registered 4 March 2015. PMID- 26857823 TI - The role of advocacy in promoting better child health. PMID- 26857822 TI - Comparison of the corneal biomechanical properties, optic nerve head topographic parameters, and retinal nerve fiber layer thickness measurements in diabetic and non-diabetic primary open-angle glaucoma. AB - The purpose of this study is to investigate the corneal biomechanical properties, optic nerve head (ONH) topographic parameters, and retinal nerve fiber layer (RNFL) thickness changes in primary open-angle glaucoma (POAG) patients with and without diabetes, as well as to evaluate the effect of the metabolic control of diabetes on corneal biomechanical properties, ONH topography, and RNFL thickness. A total of 101 eyes of 101 POAG patients (60 with diabetes and 41 without diabetes) were recruited in this prospective study. Corneal hysteresis and corneal resistance factor (CRF) were both measured using the ocular response analyzer. Optic disk parameters were evaluated using the Heidelberg Retina Tomograph-III. RNFL thickness was measured by using Spectralis HRA + OCT. CRF, mean rim area, and rim volume were found to be significantly higher in the diabetic group when compared with non-diabetic group (p = 0.01 for CRF, p = 0.04 for rim area and p = 0.02 for rim volume). ANCOVA analysis showed statistically insignificant effects of age, gender, MD, and PSD values over rim area and rim volume (p > 0.05). CRF was not significantly correlated with HbA1c levels (p > 0.05). Cup area (CA), cup volume (CV), and cup shape measure (CSM) were weakly correlated with HbA1c levels (r = 0.35 and p = 0.006 for CA; r = 0.32 and p = 0.01 for CV; r = 0.32 and p = 0.01 for CSM). The difference in mean RNFL thickness values between the groups was found to be insignificant (p > 0.05). The results of this study raise doubts whether or not diabetes does in fact shield POAG patients from glaucomatous optic nerve damage from various perspectives. PMID- 26857824 TI - Poverty and child health in the UK: using evidence for action. AB - There are currently high levels of child poverty in the UK, and for the first time in almost two decades child poverty has started to rise in absolute terms. Child poverty is associated with a wide range of health-damaging impacts, negative educational outcomes and adverse long-term social and psychological outcomes. The poor health associated with child poverty limits children's potential and development, leading to poor health and life chances in adulthood. This article outlines some key definitions with regard to child poverty, reviews the links between child poverty and a range of health, developmental, behavioural and social outcomes for children, describes gaps in the evidence base and provides an overview of current policies relevant to child poverty in the UK. Finally, the article outlines how child health professionals can take action by (1) supporting policies to reduce child poverty, (2) providing services that reduce the health consequences of child poverty and (3) measuring and understanding the problem and assessing the impact of action. PMID- 26857825 TI - [Pain modulation by contextual factors in masochists: The role of the insula and parietal operculum]. PMID- 26857827 TI - Change in residential remoteness during the first 5 years of life in an Australian cerebral palsy cohort. AB - AIM: To determine if families of children with cerebral palsy living in Australia move to less remote areas between birth and 5 years. METHOD: Children on the Australian Cerebral Palsy Register (n=3399) born 1996 to 2005, were assigned a remoteness value for family residence at birth and 5 years using a modification of the Australian Statistical Geography Standard. Each value at birth was subtracted from the value at 5 years yielding a positive difference if they moved more remotely, negative difference if they moved less remotely and a value of zero if they did not move or moved to an equally remote residence. RESULTS: The small net increase in remoteness across this cohort was non-significant (p=0.43). Fifty-seven per cent of families changed postcode but only 20% changed remoteness, 11% more remotely, and 9% less remotely. There was a small trend for families with a child with more impaired gross motor function (Gross Motor Function Classification System levels IV and V) to move to a less remote area. INTERPRETATION: This cohort of families with children with cerebral palsy did not appear to move to less remote areas by age 5 years. Remoteness at birth and level of gross motor function seem to have little effect. PMID- 26857829 TI - Effectiveness of a Multicomponent Sun Protection Program for Young Children: A Randomized Clinical Trial. AB - IMPORTANCE: Emphasizing sun protection behaviors among young children may minimize sun damage and foster lifelong sun protection behaviors that will reduce the likelihood of developing skin cancer, especially melanoma. OBJECTIVE: To determine whether a multicomponent sun protection program delivered in pediatric clinics during the summer could increase summertime sun protection among young children. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled clinical trial with 4-week follow-up that included 300 parents or relatives (hereafter simply referred to as caregivers [mean age, 36.0 years]) who brought the child (2-6 years of age) in their care to an Advocate Medical Group clinic during the period from May 15 to August 14, 2015. Of the 300 caregiver-child pairs, 153 (51.0%) were randomly assigned to receive a read-along book, swim shirt, and weekly text message reminders related to sun protection behaviors (intervention group) and 147 (49.0%) were randomly assigned to receive the information usually provided at a well-child visit (control group). Data analysis was performed from August 20 to 30, 2015. INTERVENTION: Multicomponent sun protection program composed of a read along book, swim shirt, and weekly text-message reminders related to sun protection behaviors. MAIN OUTCOMES AND MEASURES: Outcomes were caregiver reported use of sun protection by the child (seeking shade and wearing sun protective clothing and sunscreen) using a 5-point Likert scale, duration of outdoor activities, and number of children who had sunburn or skin irritation. The biologic measurement of the skin pigment of a child's arm was performed with a spectrophotometer at baseline and 4 weeks later. RESULTS: Of the 300 caregiver child pairs, the 153 children in the intervention group had significantly higher scores related to sun protection behaviors on both sunny (mean [SE], 15.748 [0.267] for the intervention group; mean [SE], 14.780 [0.282] for the control group; mean difference, 0.968) and cloudy days (mean [SE], 14.286 [0.282] for the intervention group; mean [SE], 12.850 [0.297] for the control group; mean difference, 1.436). Examination of pigmentary changes by spectrophotometry revealed that the children in the control group significantly increased their melanin levels, whereas the children in the intervention group did not have a significant change in melanin level on their protected upper arms (P < .001 for skin type 1, P = .008 for skin type 2, and P < .001 for skin types 4-6). CONCLUSIONS AND RELEVANCE: A multicomponent intervention using text-message reminders and distribution of read-along books and swim shirts was associated with increased sun protection behaviors among young children. This was corroborated by a smaller change in skin pigment among children receiving the intervention. This implementable program can help augment anticipatory sun protection guidance in pediatric clinics and decrease children's future skin cancer risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02376517. PMID- 26857830 TI - Evaluation of maternal and perinatal outcomes among overweight women who experienced stillbirth. AB - OBJECTIVE: To investigate associations between overweight and adverse clinical outcomes among women who experienced stillbirth. METHODS: 234 pregnant women (stillbirth group, n = 115; live birth group, n = 119) were included in this retrospective case-control study. Recorded risk factors were age, gravidity, parity, gestational weeks, fetal birth weight, gestational diabetes mellitus (GDM), preeclampsia (PE), intrauterine growth restriction (IUGR), levels of prenatal test markers (alpha-fetoprotein (AFP), pregnancy-associated plasma protein, human chorionic gonadotropin (beta-hCG) and E3) and body mass index (BMI). RESULTS: Statistically significant differences were observed between the groups in terms of birth weight, IUGR, GDM, PE, AFP level, beta-hCG level, maternal E3 level and BMI (p < 0.05). Subgroup analyses revealed that 34 and 81 patients in the stillbirth group were of normal weight and overweight, respectively, fetal birth weight, IUGR, GDM, PE, AFP level, beta-hCG level and E3 level differed significantly between these subgroups and the live birth group (p < 0.05). CONCLUSIONS: Women who experience stillbirth tend to be more overweight than those who experience live birth. Additionally, IUGR, GDM and PE are more common among overweight women. Therefore, overweight women should be encouraged to lose weight before pregnancy. If they become pregnant without losing weight, they should be followed up closely to avoid adverse perinatal outcomes. PMID- 26857828 TI - In vitro cytotoxic screening of 31 crude extracts of Thai herbs on a chondrosarcoma cell line and primary chondrocytes and apoptotic effects of selected extracts. AB - Thirty-one dichloromethane and methanol crude extracts of 16 herb species used in Thai traditional folk medicine were studied for their cytotoxic activities on the SW 1353 chondrosarcoma cell line and primary chondrocytes. Methyl thiazolyl tetrazolium (MTT) cell viability assay and flow cytometric method were used as screening tools for cytotoxicity testing. The half maximal inhibitory concentration (IC50) was measured and reported for each crude extract. Apoptosis, necrosis, and cell viability were measured by flow cytometry at IC50. Two out of 31 herbal extracts, methanol extracts of Paris polyphylla var. chinensis and Ficus thailandica C.C. Berg & S. Gardner, showed potent anticancer activity. They demonstrated high apoptosis induction activity in SW 1353 cells but had less effect on percentage of viability and necrosis of normal chondrocyte cells. Cytotoxic screening and apoptosis assays suggest the potential anticancer activity of some plants used in Thai traditional medicine and provide information concerning their direct effects. PMID- 26857831 TI - Erratum to: Atlantic Diabetes in Pregnancy (DIP): the prevalence and outcomes of gestational diabetes mellitus using new diagnostic criteria. PMID- 26857833 TI - Sandwiched assembly of ZnO nanowires between graphene layers for a self-powered and fast responsive ultraviolet photodetector. AB - A heterostructure of graphene and zinc oxide (ZnO) nanowires (NWs) is fabricated by sandwiching an array of ZnO NWs between two graphene layers for an ultraviolet (UV) photodetector. This unique structure allows NWs to be in direct contact with the graphene layers, minimizing the effect of the substrate or metal electrodes. In this device, graphene layers act as highly conducting electrodes with a high mobility of the generated charge carriers. An excellent sensitivity is demonstrated towards UV illumination, with a reversible photoresponse even for a short period of UV illumination. Response and recovery times of a few milliseconds demonstrated a much faster photoresponse than most of the conventional ZnO nanostructure-based photodetectors. It is shown that the generation of a built-in electric field between the interface of graphene and ZnO NWs effectively contributes to the separation of photogenerated electron-hole pairs for photocurrent generation without applying any external bias. Upon application of external bias voltage, the electric field further increases the drift velocity of photogenerated electrons by reducing the charge recombination rates, and results in an enhancement of the photocurrent. Therefore, the graphene based heterostructure (G/ZnO NW/G) opens avenues to constructing a novel heterostructure with a combination of two functionally dissimilar materials. PMID- 26857832 TI - Prospective analysis of association between statins and pancreatic cancer risk in the Women's Health Initiative. AB - PURPOSE: To determine whether HMG-CoA reductase inhibitors (statins) are associated with a lower risk of pancreatic cancer. METHODS: The population included 160,578 postmenopausal women enrolled in the Women's Health Initiative (WHI) in which 385 incident cases of pancreatic cancer were identified over an average of 8.69 (SD +/-4.59) years. All diagnoses were confirmed by medical record and pathology review. Information on statin use and other risk factors was collected at baseline and during follow-up. Multivariable-adjusted hazards ratios (HRs) and 95 % confidence intervals (CIs) evaluating the relationship between prior statin use (at baseline only as well as in a time-dependent manner) and risk of pancreatic cancer were computed from Cox proportional hazards regression analyses after adjusting for appropriate confounders. We also evaluated the effect of statin type, potency, lipophilic status, and duration of use. All statistical tests were two-sided. RESULTS: Statins were used at baseline by 12,243 (7.5 %) women. The annualized rate of pancreatic cancer in statin users and nonusers, respectively, was 0.0298 versus 0.0271 %. The multivariable adjusted HR for statin users versus nonusers at baseline was 0.92 and 95 % CI 0.57-1.48. In a time-dependent model, the HR for low-potency statins was 0.46, 95 % CI 0.20-1.04. There was no significant effect seen by statin lipophilicity or duration of use. CONCLUSIONS: There was no significant relationship between statins and pancreatic cancer risk in the WHI; however, there was a marginal inverse association noted for low-potency statins. Analyses of larger numbers of cases are needed to further explore this relationship. PMID- 26857834 TI - Simball Box for Laparoscopic Training With Advanced 4D Motion Analysis of Skills. AB - Background Laparoscopic skills training and evaluation outside the operating room is important for all surgeons learning new skills. To study feasibility, a video box trainer tracking 4-dimensional (4D) metrics was evaluated as a laparoscopic training tool. Method Simball Box is a video box trainer with authentic surgical instruments and camera with video recording, equipped with 4D motion analysis registered through trocars using machine vision technology. Residents attending a 3-day laparoscopy course were evaluated performing a laparoscopic surgical knot at start, middle, and end. Metrics were obtained. Feedback data were presented in reference to expert/tutorial performance. Results Ten right-handed residents were included. Median time (range) to finish the task was 359 (253-418), 129 (95-166), and 95 (52-156) seconds; 655%, 236%, and 174% of tutorial performance, with significance pre-/midcourse (P < .0001), pre-/postcourse (P < .0001), and mid /postcourse (P = .0050). Combined median total instrument motion decreased pre /midcourse from 1208 (845-1751) to 522 cm (411-810 cm); P = .042 to 405 cm (246 864 cm) postcourse; pre-/postcourse P < .0001; 673%, 291%, 225% of tutorial performance. Total angular distance in radians (range) was 150 (87-251), 65 (42 116), and 50 (33-136) with significance pre-/midcourse (P = .022) and pre /postcourse (P = .0002). Right-handed average speed (cm/s) increased: 1.94 (1.11 2.27) pre-, 2.39 (1.56-2.83) mid-, 2.60 (1.67-3.19) postcourse with significance pre-/midcourse (P = .022) and pre-/postcourse (P = .002). Average acceleration (mm/s(2)) and motion smoothness (um/s(3)) failed to show any difference. Conclusion For laparoscopic training and as a promising evaluation device, Simball Box obtained metrics mirroring progression well. PMID- 26857835 TI - Impact of Measurement Uncertainties on Receptor Modeling of Speciated Atmospheric Mercury. AB - Gaseous oxidized mercury (GOM) and particle-bound mercury (PBM) measurement uncertainties could potentially affect the analysis and modeling of atmospheric mercury. This study investigated the impact of GOM measurement uncertainties on Principal Components Analysis (PCA), Absolute Principal Component Scores (APCS), and Concentration-Weighted Trajectory (CWT) receptor modeling results. The atmospheric mercury data input into these receptor models were modified by combining GOM and PBM into a single reactive mercury (RM) parameter and excluding low GOM measurements to improve the data quality. PCA and APCS results derived from RM or excluding low GOM measurements were similar to those in previous studies, except for a non-unique component and an additional component extracted from the RM dataset. The percent variance explained by the major components from a previous study differed slightly compared to RM and excluding low GOM measurements. CWT results were more sensitive to the input of RM than GOM excluding low measurements. Larger discrepancies were found between RM and GOM source regions than those between RM and PBM. Depending on the season, CWT source regions of RM differed by 40-61% compared to GOM from a previous study. No improvement in correlations between CWT results and anthropogenic mercury emissions were found. PMID- 26857836 TI - Screening for Major Depressive Disorder in Children and Adolescents: A Systematic Review for the U.S. Preventive Services Task Force. AB - BACKGROUND: Major depressive disorder (MDD) is common among children and adolescents and is associated with functional impairment and suicide. PURPOSE: To update the 2009 U.S. Preventive Services Task Force (USPSTF) systematic review on screening for and treatment of MDD in children and adolescents in primary care settings. DATA SOURCES: Several electronic searches (May 2007 to February 2015) and searches of reference lists of published literature. STUDY SELECTION: Trials and recent systematic reviews of treatment, test-retest studies of screening, and trials and large cohort studies for harms. DATA EXTRACTION: Data were abstracted by 1 investigator and checked by another; 2 investigators independently assessed study quality. DATA SYNTHESIS: Limited evidence from 5 studies showed that such tools as the Beck Depression Inventory and Patient Health Questionnaire for Adolescents had reasonable accuracy for identifying MDD among adolescents in primary care settings. Six trials evaluated treatment. Several individual fair- and good-quality studies of fluoxetine, combined fluoxetine and cognitive behavioral therapy, escitalopram, and collaborative care demonstrated benefits of treatment among adolescents, with no associated harms. LIMITATION: The review included only English-language studies, narrow inclusion criteria focused only on MDD, high thresholds for quality, potential publication bias, limited data on harms, and sparse evidence on long-term outcomes of screening and treatment among children younger than 12 years. CONCLUSION: No evidence was found of a direct link between screening children and adolescents for MDD in primary care or similar settings and depression or other health-related outcomes. Evidence showed that some screening tools are accurate and some treatments are beneficial among adolescents (but not younger children), with no evidence of associated harms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. PMID- 26857838 TI - Correction: Recent advances in transition metal phosphide nanomaterials: synthesis and applications in hydrogen evolution reaction. PMID- 26857837 TI - Co-activation of AKT and c-Met triggers rapid hepatocellular carcinoma development via the mTORC1/FASN pathway in mice. AB - Activation of the AKT/mTOR cascade and overexpression of c-Met have been implicated in the development of human hepatocellular carcinoma (HCC). To elucidate the functional crosstalk between the two pathways, we generated a model characterized by the combined expression of activated AKT and c-Met in the mouse liver. Co-expression of AKT and c-Met triggered rapid liver tumor development and mice required to be euthanized within 8 weeks after hydrodynamic injection. At the molecular level, liver tumors induced by AKT/c-Met display activation of AKT/mTOR and Ras/MAPK cascades as well as increased lipogenesis and glycolysis. Since a remarkable lipogenic phenotype characterizes liver lesions from AKT/c-Met mice, we determined the requirement of lipogenesis in AKT/c-Met driven hepatocarcinogenesis using conditional Fatty Acid Synthase (FASN) knockout mice. Of note, hepatocarcinogenesis induced by AKT/c-Met was fully inhibited by FASN ablation. In human HCC samples, coordinated expression of FASN, activated AKT, and c-Met proteins was detected in a subgroup of biologically aggressive tumors. Altogether, our study demonstrates that co-activation of AKT and c-Met induces HCC development that depends on the mTORC1/FASN pathway. Suppression of mTORC1 and/or FASN might be highly detrimental for the growth of human HCC subsets characterized by concomitant induction of the AKT and c-Met cascades. PMID- 26857839 TI - Cost-effectiveness of the Cardiac Component of the Focused Assessment of Sonography in Trauma Examination in Blunt Trauma. AB - BACKGROUND: Blunt cardiac injury severe enough to require surgical intervention (sBCI) is an exceedingly rare event occurring in approximately 1 out of every 1600 trauma patients. While performing the cardiac component of the Focused Assessment of Sonography in Trauma (cFAST) exam is effective in penetrating trauma, it is unclear whether it is of value in blunt trauma given the low prevalence of sBCI, the imperfect test characteristics of the FAST exam, and the rate of incidental pericardial effusion. OBJECTIVE: The objective was to determine through decision analysis whether performing the cFAST exam is cost effective in the evaluation of hypotensive and normotensive blunt trauma patients. METHODS: We created two decision analytic models using commercially available software (TreeAgePro2011) to evaluate the cost-effectiveness of the cFAST in hypotensive (systolic blood pressure <90 mm Hg) and normotensive blunt trauma patients. Clinical probabilities were obtained from published data. Costs were estimated from Medicare reimbursement and charge data. The willingness-to pay threshold was $50,000/quality-adjusted life-years (QALYs). Sensitivity analyses were performed over plausible ranges using available literature. RESULTS: In hypotensive patients, for the base case scenario of a 34-year-old with blunt trauma, the cFAST strategy had a cost of $42,882.70 and an effectiveness of 25.3597 QALYs, whereas the no cFAST strategy had a cost of $42,753.52 and an effectiveness of 25.3532 QALYs. The incremental cost effectiveness ratio (ICER) was $19,918/QALY. For normotensive patients the cFAST strategy had a cost of $18,331.03 and an effectiveness of 23.2817 QALYs, whereas the no cFAST strategy had a cost of $18,207.58 and an effectiveness of 23.2814 QALYs. The ICER was $465,867/QALY. In the sensitivity analyses, age, probability of death from sBCI with prompt treatment, and probability of sBCI were the main drivers of variability in the model outcomes. CONCLUSIONS: The cFAST for blunt trauma is cost-effective for hypotensive but not for normotensive patients. The ICER for hypotensive patients was more than 20 times higher than the ICER for normotensive patients. Our results suggest that performing the cFAST exam may not be an effective use of resources in normotensive blunt trauma patients. PMID- 26857840 TI - Effects of glucose metabolism during in vitro maturation on cytoplasmic maturation of mouse oocytes. AB - Although there are many reports on the effect of glucose metabolism on oocyte nuclear maturation, there are few studies on its effect on ooplasmic maturation. By manipulating glucose metabolism pathways using a maturation medium that could support oocyte nuclear maturation but only a limited blastocyst formation without glucose, this study determined effects of glucose metabolism pathways on ooplasmic maturation. During maturation of cumulus-oocyte-complexes (COCs) with glucose, the presence of PPP inhibitor, DHEA or glycolysis inhibitor, iodoacetate significantly decreased blastocyst rates, intraoocyte glutathione and ATP. While blastocyst rates, GSH/GSSG ratio and NADPH were higher, ROS was lower significantly in COCs matured with iodoacetate than with DHEA. Fructose-6 phosphate overcame the inhibitory effect of DHEA on PPP. During maturation of COCs with pyruvate, electron transport inhibitor, rotenone or monocarboxylate transfer inhibitor, 4-CIN significantly decreased blastocyst rates. Cumulus denuded oocytes had a limited capacity to use glucose or lactate, but they could use pyruvate to support maturation. In conclusion, whereas glycolysis promoted ooplasmic maturation mainly by supplying energy, PPP facilitated ooplasmic maturation to a greater extent by both reducing oxidative stress and supplying energy through providing fructose-6-phosphate for glycolysis. Pyruvate was transferred by monocarboxylate transporters and utilized through mitochondrial electron transport to sustain ooplasmic maturation. PMID- 26857841 TI - Plasticity of intrinsic excitability in mature granule cells of the dentate gyrus. AB - The dentate gyrus is the main entry gate for cortical input to the hippocampus and one of the few brain areas where adult neurogenesis occurs. Several studies have shown that it is relatively difficult to induce synaptic plasticity in mature but not in newborn dentate granule cells. In the present work we have systematically addressed how classical protocols to induce synaptic plasticity affect action potential firing and intrinsic excitability in mature granule cells. We found that stimulation paradigms considered to be relevant for learning processes consistently modified the probability to generate action potentials in response to a given synaptic input in mature cells, in some paradigms even without any modification of synaptic strength. Collectively the results suggest that plasticity of intrinsic dendritic excitability has a lower induction threshold than synaptic plasticity in mature granule cells and that this form of plasticity might be an important mechanism by which mature granule cells contribute to hippocampal function. PMID- 26857842 TI - AAV-mediated Gene Therapy Halts Retinal Degeneration in PDE6beta-deficient Dogs. AB - We previously reported that subretinal injection of AAV2/5 RK.cpde6beta allowed long-term preservation of photoreceptor function and vision in the rod-cone dysplasia type 1 (rcd1) dog, a large animal model of naturally occurring PDE6beta deficiency. The present study builds on these earlier findings to provide a detailed assessment of the long-term effects of gene therapy on the spatiotemporal pattern of retinal degeneration in rcd1 dogs treated at 20 days of age. We analyzed the density distribution of the retinal layers and of particular photoreceptor cells in 3.5-year-old treated and untreated rcd1 dogs. Whereas no rods were observed outside the bleb or in untreated eyes, gene transfer halted rod degeneration in all vector-exposed regions. Moreover, while gene therapy resulted in the preservation of cones, glial cells and both the inner nuclear and ganglion cell layers, no cells remained in vector-unexposed retinas, except in the visual streak. Finally, the retinal structure of treated 3.5-year-old rcd1 dogs was identical to that of unaffected 4-month-old rcd1 dogs, indicating near complete preservation. Our findings indicate that gene therapy arrests the degenerative process even if intervention is initiated after the onset of photoreceptor degeneration, and point to significant potential of this therapeutic approach in future clinical trials. PMID- 26857843 TI - Genetic Manipulation of Brown Fat Via Oral Administration of an Engineered Recombinant Adeno-associated Viral Serotype Vector. AB - Recombinant adeno-associated virus (rAAV) vectors are attractive vehicles for gene therapy. Gene delivery to the adipose tissue using naturally occurring AAV serotypes is less successful compared to liver and muscle. Here, we demonstrate that oral administration of an engineered serotype Rec2 led to preferential transduction of brown fat with absence of transduction in the gastrointestinal track. Among the six natural and engineered serotypes being compared, Rec2 was the most efficient serotype achieving high level transduction at a dose 1~2 orders lower than reported doses for systemic administration. Overexpressing vascular endothelial growth factor (VEGF) in brown fat via oral administration of Rec2-VEGF vector increased the brown fat mass and enhanced thermogenesis. In contrast, knockdown VEGF in brown fat of VEGF (loxP) mice via Rec2-Cre vector hampered cold response and decreased brown fat mass. Oral administration of Rec2 vector provides a novel tool to genetically manipulate brown fat for research and therapeutic applications. PMID- 26857844 TI - One-step generation of triple gene-targeted pigs using CRISPR/Cas9 system. AB - Pig shows multiple superior characteristics in anatomy, physiology, and genome that have made this species to be more suitable models for human diseases, especially for neurodegenerative diseases, because they have similar cerebral convolutions compared with human neocortex. Recently, CRISPR/Cas9 system shows enormous potential for engineering the pig genome. In this study, we expect to generate human Parkinson's disease pig model using CRISPR/Cas9 system by simultaneously targeting three distinct genomic loci, parkin/DJ-1/PINK1, in Bama miniature pigs. By co-injection of Cas9 mRNA and multiplexing single guide RNAs (sgRNAs) targeting parkin, DJ-1, and PINK1 genes, respectively, into in vivo derived pronuclear embryos, we simultaneously targeted three distinct genomic loci. The gene modified piglets remain healthy and display normal behavior at the age of 10 months. In addition, despite the high number of sgRNAs were employed in the present study, our trio-based whole-genome sequencing analysis suggested that the incidence of off-target events is low. Our results demonstrate that the simplicity, efficiency, and power of the CRISPR/Cas9 system to allow for the modification of multiple genes in pigs and yield results of high medical value. PMID- 26857845 TI - Dietary soy and meat proteins induce distinct physiological and gene expression changes in rats. AB - This study reports on a comprehensive comparison of the effects of soy and meat proteins given at the recommended level on physiological markers of metabolic syndrome and the hepatic transcriptome. Male rats were fed semi-synthetic diets for 1 wk that differed only regarding protein source, with casein serving as reference. Body weight gain and adipose tissue mass were significantly reduced by soy but not meat proteins. The insulin resistance index was improved by soy, and to a lesser extent by meat proteins. Liver triacylglycerol contents were reduced by both protein sources, which coincided with increased plasma triacylglycerol concentrations. Both soy and meat proteins changed plasma amino acid patterns. The expression of 1571 and 1369 genes were altered by soy and meat proteins respectively. Functional classification revealed that lipid, energy and amino acid metabolic pathways, as well as insulin signaling pathways were regulated differently by soy and meat proteins. Several transcriptional regulators, including NFE2L2, ATF4, Srebf1 and Rictor were identified as potential key upstream regulators. These results suggest that soy and meat proteins induce distinct physiological and gene expression responses in rats and provide novel evidence and suggestions for the health effects of different protein sources in human diets. PMID- 26857847 TI - The effects of different suture materials in the nasal cavity. AB - OBJECTIVE: To investigate the effects of different suture materials in the nasal cavity on encrustation and micro-organism colonisation. METHODS: Four different suture materials were used to suture the nasal septum. The effects of suture materials on intranasal encrustation were evaluated with anterior rhinoscopy. The sutures were removed and evaluated in terms of micro-organism colonisation on the 7th and 21st post-operative days. RESULTS: Monofilament sutures were found to cause less encrustation and micro-organism colonisation. There was increased late stage encrustation if an absorbable monofilament suture remained in place for a long time. The removal of a non-absorbable monofilament suture in the early or late post-operative period made no difference in terms of micro-organism growth on the suture. CONCLUSION: The material and physical characteristics of sutures placed inside the nose may indirectly affect the healing process. It may be more appropriate to use different materials depending on the length of time the suture is to remain in place. PMID- 26857846 TI - Host Stress Drives Salmonella Recrudescence. AB - Host stress is well known to result in flare-ups of many bacterial, viral and parasitic infections. The mechanism by which host stress is exploited to increase pathogen loads, is poorly understood. Here we show that Salmonella enterica subspecies enterica serovar Typhimurium employs a dedicated mechanism, driven by the scsA gene, to respond to the host stress hormone cortisol. Through this mechanism, cortisol increases Salmonella proliferation inside macrophages, resulting in increased intestinal infection loads in DBA/2J mice. ScsA directs overall Salmonella virulence gene expression under conditions that mimic the intramacrophagic environment of Salmonella, and stimulates the host cytoskeletal alterations that are required for increased Salmonella proliferation inside cortisol exposed macrophages. We thus provide evidence that in a stressed host, the complex interplay between a pathogen and its host endocrine and innate immune system increases intestinal pathogen loads to facilitate pathogen dispersal. PMID- 26857848 TI - Double spinal cord lesions and pelvic floor electrophysiology. PMID- 26857849 TI - The microRNA expression profile in porcine skeletal muscle is changed by constant heat stress. AB - Heat stress has profound effects on animal performance and muscle function, and microRNAs (miRNAs) play a critical role in muscle development and stress responses. To characterize the changes in miRNAs in skeletal muscle responding to heat stress, the miRNA expression profiles of longissimus dorsi muscles of pigs raised under constant heat stress (30 degrees C; n = 8) or control temperature (22 degrees C; n = 8) for 21 days were analyzed by Illumina deep sequencing. A total of 58 differentially expressed miRNAs were identified with 30 down regulated and 28 up-regulated, and 63 differentially expressed target genes were predicted by miRNA-mRNA joint analysis. GO and KEGG analyses showed that the genes regulated by differentially expressed miRNAs were enriched in glucose metabolism, cytoskeletal structure and function and stress response. Real-time PCR showed that the mRNA levels of PDK4, HSP90 and DES were significantly increased, whereas those of SCD and LDHA significantly decreased by heat exposure. The protein levels of CALM1, DES and HIF1alpha were also significantly increased by constant heat. These results demonstrated that the change in miRNA expression in porcine longissimus dorsi muscle underlies the changes in muscle structure and metabolism in porcine skeletal muscle affected by constant heat stress. PMID- 26857850 TI - What is happening to health in the economic downturn? A view of the Lisbon Metropolitan Area, Portugal. AB - BACKGROUND: The economic downturn has introduced new social risks in the most affected countries with foreseeable negative consequences for health. AIM: To analyse changes in health and its socioeconomic inequalities between 2001-2011 in the Lisbon Metropolitan Area (LMA), Portugal. SUBJECTS AND METHODS: This study, conducted in the LMA neighbourhoods (n = 207), examines the association between deprivation and premature mortality using standardised premature mortality ratios and a composite index of socioeconomic deprivation. The association was observed by analysing the whole range of values, quintiles and deciles of the LMA population. Pearson coefficients and ANOVA were used to assess associations and variability between quintiles/deciles. RESULTS: The findings show that people living in extreme deprivation conditions increased (5.45%) and that increasing deprivation is associated with health degradation in specific groups. Between 2001-2011, premature mortality became more unequally distributed, increasing in the richest (1%) and median (12%) areas, even though socioeconomic inequalities in mortality decreased. CONCLUSIONS: Health degradation is selective, affecting mainly the middle class living in LMA; these 'newly deprived' people experience an increased risk, while the 'traditionally deprived' show no decrease in premature mortality. Therefore, social inequalities in health tend to decrease, but without health gains. PMID- 26857851 TI - An evaluation of portion size estimation aids: precision, ease of use and likelihood of future use. AB - OBJECTIVE: The present study aimed to evaluate the precision, ease of use and likelihood of future use of portion size estimation aids (PSEA). DESIGN: A range of PSEA were used to estimate the serving sizes of a range of commonly eaten foods and rated for ease of use and likelihood of future usage. SETTING: For each food, participants selected their preferred PSEA from a range of options including: quantities and measures; reference objects; measuring; and indicators on food packets. These PSEA were used to serve out various foods (e.g. liquid, amorphous, and composite dishes). Ease of use and likelihood of future use were noted. The foods were weighed to determine the precision of each PSEA. SUBJECTS: Males and females aged 18-64 years (n 120). RESULTS: The quantities and measures were the most precise PSEA (lowest range of weights for estimated portion sizes). However, participants preferred household measures (e.g. 200 ml disposable cup) - deemed easy to use (median rating of 5), likely to use again in future (all scored either 4 or 5 on a scale from 1='not very likely' to 5='very likely to use again') and precise (narrow range of weights for estimated portion sizes). The majority indicated they would most likely use the PSEA preparing a meal (94 %), particularly dinner (86 %) in the home (89 %; all P<0.001) for amorphous grain foods. CONCLUSIONS: Household measures may be precise, easy to use and acceptable aids for estimating the appropriate portion size of amorphous grain foods. PMID- 26857852 TI - Surgical complications after simultaneous pancreas-kidney transplantation: A single-center experience. AB - BACKGROUND: We investigated the rate of early surgical complications after simultaneous pancreas-kidney transplantation (SPKT) and their impact on both grafts and recipient survival. MATERIALS AND METHODS: The retrospective analysis of typical pancreas-related complications, different methods of correction, and their efficacy were performed. Data describing pancreas transplant recipients were drawn from our SPKT waiting list. RESULTS: The overall surgical complications rate was 37.5%. The 1-year pancreas graft survival was 82.5% and 1 year recipient survival was 90%. Surgical complications based on the graft loss rate did not exceed 2.5%. Direct surgical complications did not account for the loss of a single patient. CONCLUSION: We conclude that the high rate of surgical complications is a major obstacle to widespread application of pancreas transplantation; early recognition and appropriate treatment of graft-related complications is fundamental for graft survival. PMID- 26857853 TI - Influence of meteorological factors on acute aortic events in a subtropical territory. AB - BACKGROUND/OBJECTIVE: This study aims to examine the relationship between weather changes and acute aortic events in a subtropical territory. METHODS: A linear regression analysis was performed in a pan-territory epidemiological survey for a period of 10 years on the impacts of meteorological factors (ambient temperature, atmospheric pressure, relative humidity, amount of cloud, rainfall, number of lightning strikes, presence of typhoon, and thunderstorm warning) on the daily incidences of acute aortic dissections and ruptured aortic aneurysms. Meteorological variables were retrieved on a daily basis from a well-established observatory, and the daily incidences of aortic dissections and rupture of aortic aneurysms were retrieved from the Clinical Data Analysis and Reporting System. RESULTS: During the study period (January 2005 to December 2014), 3878 patients were identified as having acute aortic dissections, and 1174 patients had ruptured aortic aneurysms. Corresponding averaged daily incidences were 1.06 and 0.32, respectively. The incidences of aortic dissection and ruptured aortic aneurysm in a day could be predicted by ambient temperature in degrees Celsius using the following linear regression models: (1) incidence of aortic dissection = 1.548 - 0.021 * temperature; (2) incidence of ruptured aortic aneurysm = 0.564 0.010 * temperature. In addition, both high atmospheric pressure and absence of thunderstorm warning are positively associated with more aortic dissections. For rupture of aortic aneurysms, high atmospheric pressure and low relative humidity were positive predictors. In multiple regression analysis, however, ambient temperature was the only significant predictor for both acute aortic dissections and ruptured aortic aneurysms. CONCLUSION: This is the first pan-territory study to show an attributable effect of ambient temperature on acute aortic events. This paper confirms that even in a subtropical country, meteorological variables were important factors influencing acute aortic events. PMID- 26857855 TI - Identification and Functional Characterization of a Fructooligosaccharides Forming Enzyme from Aspergillus aculeatus. AB - Although fructosyltransferases from Aspergillus aculeatus have received a considerable interest for the prebiotics industry, their amino acid sequences and structural features remain unknown. This study sequenced and characterized a fructosyltransferase from A. aculeatus (AcFT) isolated by heat treatment of Pectinex Ultra SP-L. The AcFT enzyme showed two isoforms, low-glycosylated AcFT1 and high-glycosylated AcFT2 forms, with similar optimum activity at 60 degrees C. The purified heat-resistant AcFT1 and AcFT2 isoforms produced identical patterns of fructooligosaccharides (FOS; kestose, nystose and fructosylnystose) with a notable transfructosylation capability (~90 % transferase/hydrolase ratio). In contrast, the pI and optimum pH values exhibited discrete differences, attributable to their glycosylation pattern. Partial protein sequencing showed that AcFT enzyme corresponds to Aspac1_37092, a putative 654-residue fructosyltransferase encoded in the genome of A. aculeatus ATCC16872. A homology model of AcFT also revealed the typical fold common to members of the glycoside hydrolase family 32 (GH32), with an N-terminal five-blade beta-propeller domain enclosing catalytic residues D60, D191, and E292, linked to a C-terminal beta sandwich domain. To our knowledge, this is the first report describing the amino acid sequence and structural features of a heat-resistant FOS-forming enzyme from A. aculeatus, providing insights into its potential applications in the prebiotics industry. PMID- 26857854 TI - Methylation-based classification of benign and malignant peripheral nerve sheath tumors. AB - The vast majority of peripheral nerve sheath tumors derive from the Schwann cell lineage and comprise diverse histological entities ranging from benign schwannomas and neurofibromas to high-grade malignant peripheral nerve sheath tumors (MPNST), each with several variants. There is increasing evidence for methylation profiling being able to delineate biologically relevant tumor groups even within the same cellular lineage. Therefore, we used DNA methylation arrays for methylome- and chromosomal profile-based characterization of 171 peripheral nerve sheath tumors. We analyzed 28 conventional high-grade MPNST, three malignant Triton tumors, six low-grade MPNST, four epithelioid MPNST, 33 neurofibromas (15 dermal, 8 intraneural, 10 plexiform), six atypical neurofibromas, 43 schwannomas (including 5 NF2 and 5 schwannomatosis associated cases), 11 cellular schwannomas, 10 melanotic schwannomas, 7 neurofibroma/schwannoma hybrid tumors, 10 nerve sheath myxomas and 10 ganglioneuromas. Schwannomas formed different epigenomic subgroups including a vestibular schwannoma subgroup. Cellular schwannomas were not distinct from conventional schwannomas. Nerve sheath myxomas and neurofibroma/schwannoma hybrid tumors were most similar to schwannomas. Dermal, intraneural and plexiform neurofibromas as well as ganglioneuromas all showed distinct methylation profiles. Atypical neurofibromas and low-grade MPNST were indistinguishable with a common methylation profile and frequent losses of CDKN2A. Epigenomic analysis finds two groups of conventional high-grade MPNST sharing a frequent loss of neurofibromin. The larger of the two groups shows an additional loss of trimethylation of histone H3 at lysine 27 (H3K27me3). The smaller one retains H3K27me3 and is found in spinal locations. Sporadic MPNST with retained neurofibromin expression did not form an epigenetic group and most cases could be reclassified as cellular schwannomas or soft tissue sarcomas. Widespread immunohistochemical loss of H3K27me3 was exclusively seen in MPNST of the main methylation cluster, which defines it as an additional useful marker for the differentiation of cellular schwannoma and MPNST. PMID- 26857856 TI - Identification of a highly immunogenic mouse breast cancer sub cell line, 4T1-S. AB - Cancer vaccines serve as a promising clinical immunotherapeutic strategy that help to trigger an effective and specific antitumor immune response compared to conventional therapies. However, poor immunogenicity of tumor cells remains a major obstacle for clinical application, and developing new methods to modify the immunogenicity of tumor cells may help to improve the clinical outcome of cancer vaccines. 4T1 mouse breast cancer cell line has been known as poorly immunogenic and highly metastatic cell line. Using this model, we identified a sub cell line of 4T1-designated as 4T1-Sapporo (4T1-S)-which shows immunogenic properties when used as a vaccine against the same line. In 4T1-S-vaccinated mice, subcutaneous injection of 4T1-S resulted in an antitumor inflammatory response represented by significant enlargement of draining lymph nodes, accompanied with increased frequencies of activated CD8 T cells and a subpopulation of myeloid cells. Additionally, 4T1-S vaccine was ineffective to induce tumor rejection in nude mice, which importantly indicate that 4T1-S vaccine rely on T cell response to induce tumor rejection. Further analysis to identify mechanisms that control tumor immunogenicity in this model may help to develop new methods for improving the efficacies of clinical cancer vaccines. PMID- 26857857 TI - Simple and Sensitive Molecularly Imprinted Polymer - Mn-Doped ZnS Quantum Dots Based Fluorescence Probe for Cocaine and Metabolites Determination in Urine. AB - A new molecularly imprinted polymer (MIP)-based fluorescent artificial receptor has been prepared by anchoring a selective MIP for cocaine (COC) on the surface of polyethylene glycol (PEG) modified Mn-doped ZnS quantum dots (QDs). The prepared material combines the high selectivity attributed to MIPs and the sensitive fluorescent property of the Mn-doped ZnS QDs. Simple and low cost methods have therefore been optimized for assessing cocaine abuse in urine by monitoring the fluorescence quenching when the template (COC) and also metabolites from COC [benzoylecgonine (BZE) and ecgonine methyl ester (EME)] are present. Fluorescence quenching was not observed when performing experiments with other drugs of abuse (and their metabolites) or when using nonimprinted polymer (NIP)-coated QDs. Under optimized operating conditions (1.5 mL of 200 mg L(-1) MIP-coated QDs solution, pH 5.5, and 15 min before fluorescence scanning) two analytical methods were developed/validated. One of the procedures (direct method) consisted of urine sample 1:20 dilution before fluorescence measurements. The method has been found to be fast, precise, and accurate, but the standard addition technique for performing the analysis was required because of the existence of matrix effect. The second procedure performed a solid phase extraction (SPE) first, avoiding matrix effect and allowing external calibration. The limits of detection of the methods were 0.076 mg L(-1) (direct method) and 0.0042 mg L(-1) (SPE based method), which are lower than the cutoff values for confirmative conclusions regarding cocaine abuse. PMID- 26857858 TI - Genetically lowered concentrations of circulating sRAGE might cause an increased risk of cancer: Meta-analysis using Mendelian randomization. AB - OBJECTIVES: To undertake a systematic meta-analysis of all variants in the gene encoding receptor for advanced glycation end products (RAGE) to summarize their associations with cancer risk and changes in the levels of circulating soluble RAGE (sRAGE), with the aim of determining possible causality between circulating sRAGE and cancer risk. METHODS: Articles written in English were retrieved from MEDLINE(r) and EMBASE(r) databases. Two researchers independently identified eligible articles and extracted the data (analysed using STATA(r) software version 12.0). RESULTS: Fifteen articles qualified for inclusion in the meta analysis of the RAGE-cancer association and three examined the RAGE-sRAGE relationship. The 82Ser/82Ser genotype was significantly associated with overall cancer risk compared with the 82Gly/Gly genotype (odds ratio 1.75, 95% confidence interval [CI] 1.46, 2.10). Carriers of the 82Ser/82Ser genotype had significantly reduced circulating sRAGE concentrations compared with the 82Gly/82Gly genotype. Mendelian randomization analysis demonstrated that a reduction of 100, 200 and 300 pg/ml in circulating sRAGE concentrations was associated with a 1.11-fold (95% CI 1.06, 1.25), 1.24-fold (95% CI 1.11, 1.57) and 1.38-fold (95% CI 1.18, 1.96) increased risk of developing cancer, respectively. CONCLUSIONS: Genetically lowered concentrations of circulating sRAGE might cause an increased risk of cancer. PMID- 26857859 TI - Prevalence rate and influencing factors of preoperative anxiety and depression in gastric cancer patients in China: Preliminary study. AB - OBJECTIVES: To investigate the prevalence rate and influencing factors of preoperative anxiety and depression in patients with gastric cancer, in China. METHODS: Patients with gastric cancer who were diagnosed by gastroscopy and would accept laparoscopic surgery were eligible for the study. Each participant completed self-administered questionnaires, including the Hospital Anxiety and Depression Scale (HADS), Medical Coping Modes Questionnaire (MCMQ), Social Support Rating Scale, and Type D personality scale before surgery. Routine blood tests were undertaken within 7 days before surgery, to calculate the neutrophil to-lymphocyte ratio (NLR). Based on HADS, patients were divided into an anxiety/depression group and a nonanxiety/depression group. RESULTS: Fifty-three patients with gastric cancer were included in the study. The prevalence of preoperative anxiety and/or depression was 20.75% (11/53). Factors influencing preoperative anxiety and depression were a resigned dimension of coping style, type D personality and NLR. Logistic regression analysis showed that a higher score for the resigned dimension of coping style on the MCMQ and a higher NLR were significantly associated with preoperative anxiety and depression. CONCLUSIONS: The prevalence of preoperative anxiety and depression in Chinese patients with gastric cancer may be influenced by both the coping mode and NLR. PMID- 26857860 TI - Resistin: New serum marker for predicting severity of acute pancreatitis. AB - OBJECTIVE: To assess the effectiveness of resistin in predicting the severity of acute pancreatitis. METHODS: Patients with acute pancreatitis who presented at the Gastroenterology Clinic, Erzurum Education and Research Hospital, Turkey were enrolled in this prospective study. White blood cell (WBC), C-reactive protein (CRP) and resistin levels were measured on admission and at 24 h, day 3 and day 7 following admission, along with other blood parameters. Patients were divided into two groups: mild acute pancreatitis and moderate/severe acute pancreatitis. RESULTS: Of 59 patients with acute pancreatitis (mild, n = 37; moderate/severe, n = 22), significant between-group differences were found in terms of resistin and CRP levels. Receiver operating curve analysis showed that resistin levels were better for predicting severe cases of acute pancreatitis than CRP or WBC levels on day 3 (area under the curve [AUC], 0.88 versus 0.81 and 0.63, respectively). Resistin levels on day 3 were better than CRP levels for predicting necrosis development (AUC, 0.70 versus 0.69, respectively). CONCLUSIONS: Resistin may represent a new, effective indicator to predict the severity of acute pancreatitis and presence of necrosis in patients with acute pancreatitis. PMID- 26857861 TI - Serum cross-linked N-telopeptide of type I collagen for the diagnosis of bone metastases from solid tumours in the Chinese population: Meta-analysis. AB - OBJECTIVE: A meta-analysis to determine the diagnostic value of serum cross linked N-telopeptide of type I collagen (NTx) for bone metastasis from solid tumours in the Chinese population. METHODS: Eligible case-control studies published up until 22 September 2014 were identified by searching the electronic literature databases PubMed(r), Web of Science, China National Knowledge Infrastructure and Wanfang using the keyword 'NTx' in combination with 'cancer'. A meta-analysis of the diagnostic value of serum NTx for bone metastasis from solid tumours was undertaken. RESULTS: The meta-analysis included 14 studies (1279 patients: 668 with bone metastasis; 611 controls without bone metastasis). There was a significant relationship between serum NTx concentration and bone metastasis from solid tumours in the Chinese population (odds ratio 1.39, 95% confidence intervals 1.26, 1.51). Significant heterogeneity was found in this study, but no publication bias was observed. CONCLUSION: Serum NTx concentration may play an important role in the diagnosis of bone metastasis from solid tumours in the Chinese population. PMID- 26857863 TI - Lipid profile changes after pomegranate consumption: A systematic review and meta analysis of randomized controlled trials. AB - BACKGROUND: Transport of oxidized low-density lipoprotein across the endothelium into the artery wall is considered a fundamental priming step for the atherosclerotic process. Recent studies reported potential therapeutic effects of micronutrients found in natural products, indicating positive applications for controlling the pathogenesis of chronic cardiovascular disease driven by cardiovascular risk factors and oxidative stress. A particular attention has been recently addressed to pomegranate; however findings of clinical studies have been contrasting. PURPOSE: To evaluate the effects of pomegranate consumption on plasma lipid concentrations through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: The study was designed according to the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. Scopus and Medline databases were searched to identify randomized placebo-controlled trials investigating the impact of pomegranate on plasma lipid concentrations. A fixed-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential confounders on the estimated effect sizes. RESULTS: A total of 545 individuals were recruited from the 12 RCTs. Fixed-effect meta-analysis of data from 12 RCTs (13 treatment arms) did not show any significant effect of pomegranate consumption on plasma lipid concentrations. The results of meta-regression did not suggest any significant association between duration of supplementation and impact of pomegranate on total cholesterol and HDL-C, while an inverse association was found with changes in triglycerides levels (slope: -1.07; 95% CI: -2.03 to -0.11; p = 0.029). There was no association between the amount of pomegranate juice consumed per day and respective changes in plasma total cholesterol, LDL-C, HDL-C and triglycerides. CONCLUSION: The present meta-analysis of RCTs did not suggest any effect of pomegranate consumption on lipid profile in human. PMID- 26857862 TI - Adipokine zinc-alpha-2-glycoprotein as a novel urinary biomarker presents earlier than microalbuminuria in diabetic nephropathy. AB - OBJECTIVE: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) in the early stage of diabetic nephropathy, in patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional observational study recruited patients with longstanding T2DM and healthy control subjects. Patients with T2DM were further stratified based on their urine albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Serum and urine concentrations of ZAG were determined using an enzyme-linked immunosorbent assay. RESULTS: Eighty patients with T2DM and 20 healthy control subjects were enrolled in the study. Mean +/- SD concentrations of ZAG in serum and urine were both significantly higher in patients with T2DM (serum: 38.29 +/- 22.72 mg/l; urine: 53.64 +/- 29.48 mg/g) compared with concentrations in healthy control subjects (serum: 21.61 +/- 8.83 mg/l; urine: 28.17 +/- 10.64 mg/g). Serum ZAG concentration was positively correlated with serum creatinine and eGFR. Urine ZAG concentration was positively correlated with UACR. Urine concentration of ZAG in the higher eGFR group was higher than that in the normal eGFR group (41.26 +/- 13.67 versus 32.05 +/- 8.55 mg/g, respectively). CONCLUSION: These preliminary findings suggest that ZAG might be a potentially useful biomarker for early diagnosis of diabetic nephropathy in patients with T2DM. PMID- 26857864 TI - Clinical, pathological, and molecular data on desmoplastic/nodular medulloblastoma: case studies and a review of the literature. AB - The aim of this study was to better define the clinical and biopathological features of patients with desmoplastic/nodular medulloblastoma (DNMB) and to further characterize this subgroup. 17 children aged < 5 years, with initial DNMB treated according to the HIT-SKK protocol, were evaluated. A retrospective central radiological review, a pathological and immunohistochemical study, and array-CGH and sequencing of germline SUFU and PTCH1 genes were performed. 15 histologically reviewed cases were confirmed as DNMB including three cases of medulloblastoma with extensive nodularity. Median age at diagnosis was 26 months. Radiology showed five cases with a vermis location and one with T2 hyperintensity. All cases showed a SHH immunoprofile. A 9q deletion was found in 6 cases, a MYCN-MYCL amplification in 1 case, and a SUFU germline mutation in 1 case (/9). The presence of SUFU and PTCH1 germline mutations agreed with previous reports. At 3 years, progression-free survival and overallsurvival rates were 72 +/- 15% and 85 +/- 10%, respectively. The rate of recurrence was relatively high (4 patients). This may have been because chemotherapy was delayed in two cases. Age > 3 years, and residual tumor may also have been an explanation for recurrence. PMID- 26857865 TI - Primary meningeal melanocytoma mimicking a nonfunctioning pituitary adenoma. PMID- 26857866 TI - Herbal Lead as Ideal Bioactive Compounds Against Probable Drug Targets of Ebola Virus in Comparison with Known Chemical Analogue: A Computational Drug Discovery Perspective. AB - Ebola is a deadly virus that has recently emerged as an enormous public health concern which causes dangerous illness with high fatality rates of 90 %. The virus is not receptive to known antivirals, and hence, there is a promising need to identify novel inhibitors to combat the disease. The present study deals with identification of potential herbal leads that probably subdue the activity of four major drug targets of Ebola virus such as VP24, VP30, VP35 and VP40 by computer-aided virtual screening. The selection of receptors was performed based on their functional roles in the disease. The drug likeliness and ADMET parameters of 150 herbal ligands were computationally predicted. Those molecules that qualified these parameters were preferred for docking studies with the protein targets. An existing chemical antiviral drug, BCX4430 was also docked and its theoretical binding energy was scrutinized. The docking studies suggested that herbal ligand Limonin demonstrated high binding properties with VP24 and VP35 (binding energy -9.7 kcal/mol). Similarly, curcumin exhibited good binding with VP30 (binding energy -9.6 kcal/mol). Further, Mahanine displayed superior interaction with VP40 (binding energy -7.7 kcal/mol). These herbal leads demonstrated better binding potential than the known chemical analogue in the computational studies. This study serves to bestow paramount information for further experimental studies concerning the utility of herbal ligands as probable lead molecules against Ebola viral targets. PMID- 26857867 TI - Genome-Wide Identification and Comparative Analysis of Copper Transporter Genes in Plants. AB - Copper (Cu) transporters have primary importance in maintenance of physiological limits of Cu homeostasis in plants. However, structural characterization of Cu transporters in many plant species is still limited. In this study, a total of 78 potential Cu transporter genes were identified from 18 different plant species. Study revealed that Cu transporters could be characterized with a CTR protein family (PF04145) domain, three putative transmembrane domains (TMDs), a single exon number, and a basic character. Met-rich motifs at N-terminal region, MXXXM motif in TMD-2, and GXXXG motif in TMD-3 could be essential for Cu transport since they were highly conserved in all analyzed species. In phylogeny, a clear distinction was observed between Cu transporter sequences of lower and higher plants. General topological features of Cu transporters in higher plants-monocots and dicots-were highly conserved compared to lower plants. Identification of Cu transporter homologous in various plant species and their comparative analysis at gene and protein levels will become valuable theoretical basis for future studies aiming to further characterization and molecular manipulation of Cu transporters. PMID- 26857868 TI - Magnetic resonance imaging-based measures of atlas position: Relationship to canine atlantooccipital overlapping, syringomyelia and clinical signs. AB - Canine atlantooccipital overlapping (AOO) is characterized by a decreased distance between the dorsal arch of the atlas and the supraoccipital bone. Current diagnostic criteria for this condition are subjective and clinician dependent; objective criteria are needed to allow a reliable and reproducible diagnosis in clinical and research settings and assess clinical significance. We propose four standardized MRI-based measurements to objectively assess the proximity of the atlas to the foramen magnum. Inclusion criteria for dogs in this study were bodyweight <15 kg, age >5 months, and availability of a complete MRI study performed with the craniocervical junction in extension. Exclusion criteria were space-occupying lesions and poor image quality (i.e. unclear bony margins). Measurements also included blinded determinations of skull type, presence of craniocervical junction anomalies and presence and severity of syringomyelia. Clinical status at the time of imaging was noted. Measurements were obtained in 271 dogs; these were reproducible and reliable. Findings varied by skull type: dolichocephalic dogs had smaller foramen magnum, whereas brachycephalic dogs had more cranially and dorsally positioned atlas bodies in comparison to the other skull types. Measurements also increased with increases in bodyweight. This study demonstrated a close association between AOO, syringomyelia and clinical signs. Toy and small breed dogs (including Cavalier King Charles spaniels) showed higher than previously reported prevalence of AOO; its occurrence was also associated with lower bodyweights within the study population of <15 kg toy/small breed dogs. PMID- 26857869 TI - Prediction error minimization: Implications for Embodied Cognition and the Extended Mind Hypothesis. AB - Over the past few years, the prediction error minimization (PEM) framework has increasingly been gaining ground throughout the cognitive sciences. A key issue dividing proponents of PEM is how we should conceptualize the relation between brain, body and environment. Clark advocates a version of PEM which retains, at least to a certain extent, his prior commitments to Embodied Cognition and to the Extended Mind Hypothesis. Hohwy, by contrast, presents a sustained argument that PEM actually rules out at least some versions of Embodied and Extended cognition. The aim of this paper is to facilitate a constructive debate between these two competing alternatives by explicating the different theoretical motivations underlying them, and by homing in on the relevant issues that may help to adjudicate between them. PMID- 26857870 TI - Adding a Social Marketing Campaign to a School-Based Nutrition Education Program Improves Children's Dietary Intake: A Quasi-Experimental Study. AB - BACKGROUND: Evidence supports the use of social marketing campaigns to improve nutrition knowledge and reinforce the effects of nutrition education programs. However, the additional effects of parent-focused social marketing with nutrition education have received little attention. OBJECTIVE: Our aim was to assess the impact of the Iowa Nutrition Network's school-based nutrition education program (Building and Strengthening Iowa Community Support for Nutrition and Physical Activity [BASICS]) and the benefits of adding a multichannel social marketing intervention (BASICS Plus) to increase parent-directed communication. DESIGN AND INTERVENTION: A quasi-experimental design with three study conditions compared a school-based nutrition education program (BASICS) with a school-based and social marketing intervention (BASICS Plus) and a no-treatment comparison group. PARTICIPANTS/SETTING: The study included 1,037 third-grade students attending 33 elementary schools and their parents. MAIN OUTCOME MEASURES: Measures included parents' reports of their children's in-home consumption of fruits and vegetables (F/V) and use of low-fat/fat-free milk. Data on F/V were collected using a modified version of the University of California Cooperative Extension Food Behavior Checklist; and data on milk use were collected using two questions from the National Health and Nutrition Examination Survey. STATISTICAL ANALYSES: Multilevel, mixed-effect regression models that account for correlation within repeated measures and children within school were used to compare the mean change over time in the outcome variable for one study group with the mean change over time for another study group. RESULTS: Children in BASICS increased mean consumption of fruit by 0.16 cups (P=0.04) compared with children in the comparison group. Children in BASICS Plus increased mean consumption of fruit by 0.17 cups (P=0.03) and mean consumption of vegetables by 0.13 cups (P=0.02). Children in BASICS Plus were 1.3 times (P=0.05) more likely to use low-fat/fat free milk than children in either the BASICS group or the comparison group. CONCLUSIONS: Gaining parents' attention and engaging them in healthy eating practices for their children can be a useful way to increase the effectiveness of school-based nutrition education programs. This study demonstrates the benefits of incorporating a parent-focused social marketing campaign in nutrition education interventions. PMID- 26857871 TI - Estimating the Probability of Rare Events Occurring Using a Local Model Averaging. AB - In statistical applications, logistic regression is a popular method for analyzing binary data accompanied by explanatory variables. But when one of the two outcomes is rare, the estimation of model parameters has been shown to be severely biased and hence estimating the probability of rare events occurring based on a logistic regression model would be inaccurate. In this article, we focus on estimating the probability of rare events occurring based on logistic regression models. Instead of selecting a best model, we propose a local model averaging procedure based on a data perturbation technique applied to different information criteria to obtain different probability estimates of rare events occurring. Then an approximately unbiased estimator of Kullback-Leibler loss is used to choose the best one among them. We design complete simulations to show the effectiveness of our approach. For illustration, a necrotizing enterocolitis (NEC) data set is analyzed. PMID- 26857872 TI - Calcium fortified foods or supplements for older people? PMID- 26857874 TI - Reasons for discrepancies in hip fracture risk estimates using FRAX and Garvan calculators. AB - OBJECTIVES: Both the FRAX and Garvan calculators are used to estimate absolute risk of fracture, but they sometimes produce different estimates. We sought to determine which patient characteristics contribute to these discrepancies. STUDY DESIGN: Ten-year hip fracture risk was estimated for 122 women, using both FRAX and Garvan with bone mineral density (BMD). MAIN OUTCOME MEASURES: Differences in estimates of hip fracture were assessed, both in absolute terms and with respect to a treatment threshold of 3%. RESULTS: Garvan estimates were higher than FRAX estimates across the range of ages and BMDs studied. A history of falls or of multiple fractures increased risk calculated by Garvan 3-6-fold, but did not account for all differences between calculators. Discrepancies around a 3% treatment threshold occurred in 31/122 (25%). Women aged 70-74 years, and women with osteopenia were most likely to have discordant estimates. Most discordant estimates (29/31) had a Garvan estimate >= 3% and FRAX <3%. Falls, multiple fractures, ethnicity and a history of parental hip fracture contributed to some discordant estimates. CONCLUSIONS: Hip fracture risk estimates are usually higher with Garvan than FRAX, and these differences could impact on treatment decisions in about a quarter of patients. Falls and multiple fractures have a strong influence on Garvan risk estimates, when present. Clinically important discrepancies tend to occur in patients who are at borderline fracture risk. In patients with hip fracture risks near the treatment threshold with one calculator, use of the other calculator should be considered to help guide treatment decisions. PMID- 26857873 TI - Molecular characterization and antimicrobial susceptibility of hemolytic Streptococcus agalactiae from post-menopausal women. AB - PURPOSE: Streptococcus agalactiae (Group B streptococcus, GBS) is increasingly recognized as a pathogen in adult populations, including the elderly. Appropriate treatment involves antibiotics. An alternative to this strategy would be the administration of a polysaccharide vaccine therefore the capsular serotypes and molecular characterization of circulating strains needs to be known. Few studies have been conducted in this population. METHODS: One hundred and seven GBS isolates collected from vagino-rectal swabs from 600 post-menopausal women were analysed for their capsular type, antimicrobial resistance and genetic relatedness (multilocus sequence typing, MLST). RESULTS: The colonization rate was 17.8%. Capsular type III was predominant (34.6%), followed by type V (22.4%). The most frequent sequence type (ST) was 19 (23.3%), followed by 23 (18.7%), 1 (16.8%) and 17 (12.1%). Isolates were assembled into three phylogenetic groups from ST-19, ST-23 and ST-17 founders. All isolates were susceptible to penicillin, whereas resistance to erythromycin and clindamycin was recorded in 23.4% and 20.6% of isolates, respectively. CONCLUSIONS: In our setting, the GBS colonization rate in postmenopausal women is similar to that reported in others populations studied. The population structure of these isolates is highly diverse and contains different STs. These data can contribute to the future development of a polysaccharide vaccine for preventing GBS infection in older adults. PMID- 26857875 TI - Herbal medicine (Danggui Shaoyao San) for treating primary dysmenorrhea: A systematic review and meta-analysis of randomized controlled trials. AB - Danggui Shaoyao San (DSS), a traditional herbal prescription, has long been used to treat menopause-related symptoms, including dysmenorrhea. We conducted a systematic review of randomized controlled trials to evaluate the efficacy of DSS for dysmenorrhea. We searched the following electronic databases through October 2015: PubMed; EMBASE; the Cochrane Library; AMED; five Korean databases (KoreaMed, DBPIA, OASIS, RISS, and KISS); three Chinese databases (CNKI, Wan Fang Database, and VIP), and one Japanese database (CiNii). The Cochrane criteria were used to assess the risk of bias for the individual studies. All randomized clinical trials (RCTs) of DSS or modified DSS were included. Data from all articles were extracted by two independent reviewers. Meta-analysis was used to pool the data. A total of 746 potentially relevant studies were identified, and four RCTs met our inclusion criteria. All of the included RCTs had a high risk of bias across their domains. Three RCTs showed favourable effects of DSS on response rate compared with conventional medicine, and a meta-analysis showed that DSS had superior effects compared to analgesics (RR: 1.31, 95%CI, 1.06-1.63, I(2)=73%). One RCT showed a beneficial effect of DSS on pain compared with placebo control. Our systematic review and meta-analysis provided suggestive evidence of the superiority of DSS over analgesics or placebo for dysmenorrhea. The quality of evidence for this finding was low to moderate because of a high risk of bias. PMID- 26857876 TI - Aromatase expression in human chondrocytes: An induction due to culture. AB - OBJECTIVES: Despite the high prevalence of osteoarthritis (OA) in postmenopausal women, a relationship between circulating estrogen levels and the development of OA has not been found. Therefore, the purpose of this study was to evaluate the expression and activity of aromatase, a key enzyme in local production of estrogens, in human OA cultured articular chondrocytes, and to determine the physiological relevance of this enzyme in cartilage. METHODS: Human OA articular chondrocytes were isolated and cultured. Local production of estradiol was measured after incubation with 100 ng/ml testosterone for 8 and 24h. Furthermore, chondrocytes were culture for 2h, 48 h, 7 days or 15 days, or in alginate beads for 10 days. Aromatase, type II and X collagen, aggrecan, alkaline phosphatase, and Runx2 expression were evaluated in cartilage, freshly isolated chondrocytes and cultured chondrocytes. RESULTS: Aromatase was expressed and active in cultured human chondrocytes. Human cartilage, freshly isolated chondrocytes, and chondrocytes cultured for 2h expressed an insignificant amount of aromatase; however, expression arose after 48 h of culture and remained increased thereafter. Aromatase expression was not related to estrogen deprivation and was inversely correlated with differentiation. Re-differentiation did not reduce its expression. CONCLUSIONS: Aromatase presents an almost undetectable expression in human cartilage but is induced in cultured chondrocytes. Therefore, human cartilage might act as a mere target for estrogens rather than a producer, and researchers using cell expansion in culture for latter therapies should consider these changes in estrogen metabolism which may not be reverted after re differentiation. PMID- 26857877 TI - Symptomatic pelvic floor disorders in community-dwelling older Australian women. AB - OBJECTIVES: To assess the prevalence, and factors associated with, pelvic floor disorders in a representative sample of community-dwelling older Australian women. METHODS: 1548 women, aged 65-79 years, were recruited to this cross sectional study between April and August 2014. Pelvic floor disorders, including urinary incontinence (UI), fecal incontinence (FI), and pelvic organ prolapse (POP), were assessed using validated questionnaires. Multivariable logistic regression was used to assess factors associated with each, and having one or more pelvic floor disorders. RESULTS: Among 1517 women (mean age=71.5 +/- 4.1 SD years), 47.2% (95% CI, 44.7-49.7%) of women had one or more pelvic floor disorders, with 36.2% (95% CI, 33.8-38.6%) having UI, 19.8% (95% CI, 17.8-21.9%) having FI, and 6.8% (95% CI, 5.6-8.2%) having POP. Of the women with POP, 53.4% had UI, 33% had FI and 26.2% had both. The proportion of women with one or more pelvic floor disorders increased with parity from 34.6% (95% CI, 7.8-11.7%) for nulliparous women, to 45.3% (95% CI, 40.3-59.1%) for 1-2 births, and 52.1% (95% CI, 48.3-55.8%) for >= 3 births. Obese women were more likely to have at least one pelvic floor disorder (OR=1.77; 95% CI, 1.36-2.31, p<0.01). CONCLUSION: Pelvic floor disorders are common in older women. Physicians caring for older women should be mindful that older women presenting with symptoms of one pelvic floor disorder are likely to have another concurrent pelvic floor problem. PMID- 26857878 TI - The effects of pre-operative menopausal status and hormone replacement therapy (HRT) on sexuality and quality of life after risk-reducing salpingo-oophorectomy. AB - OBJECTIVES: Investigate the effects of pre-operative menopausal status and HRT use on sexual outcomes following risk-reducing salpingo-oophorectomy (RRSO). STUDY DESIGN: Cross-sectional study of 119 women who underwent RRSO between 2009 and 2014. MAIN OUTCOME MEASURES: Data was collected via a questionnaire and serum test for testosterone and free androgen index (FAI). The questionnaire comprised demographic data and validated measures of sexual function, sexual distress, relationship satisfaction, body image, psychological stress, menopause quality of life and general quality of life. RESULTS: Rates of sexual issues were similar despite menopause status at operation. Women who were pre-menopausal at operation (mean age=44 years +/- 5) had significantly higher rates of sexual distress (p=0.020), dissatisfaction with sex life (p=0.011) and bothersome sexual menopause symptoms (p=0.04) than women who were post-menopausal (mean age=55 years +/- 7). Pre-menopausal women reported higher psychological distress from surgery (p=0.005) and poorer emotional (p=0.052) wellbeing. HRT use reduced the rates of dyspareunia (p=0.027) and the severity of sexual menopausal symptoms (p=0.030). Androgen levels were not significantly associated with desire or arousal scores. CONCLUSIONS: Regardless of menopausal status at operation, women experienced the same sexual issues at equivalent rates. However, pre-menopausal women reported higher sexual distress and dissatisfaction with sex life. Pre menopausal women also had greater psychological distress and poorer emotional function. PMID- 26857879 TI - Bone loss and wrist fractures after withdrawal of hormone therapy: The 15-year follow-up of the OSTPRE cohort. AB - CONTEXT: Long-term bone mineral density (BMD) or fracture incidence changes after withdrawal of postmenopausal hormone therapy (HT) are not well known. OBJECTIVE: To study long-term postmenopausal bone loss and incidence of wrist fracture in respect to duration and withdrawal of self-reported HT. DESIGN/SETTING: A 15-year follow-up of the population-based prospective OSTPRE cohort in Kuopio, Finland. PARTICIPANTS: Women (mean baseline age 53.4 years, range 48.1-59.6) were divided into four groups based on duration of HT: (1) never users (non-HT); (2) those who had used HT only throughout the 1st 5-year period (HT5); (3) throughout the first 10-years (HT10); (4) those who used HT throughout the entire 15-year follow-up (HT15). OUTCOME MEASURES: Femoral (n=857) and spinal (n=599) BMD measurements with dual X-ray absorptiometry (DXA) were carried out at 5-year intervals in 1989 2004. Wrist fracture incidence in 1989-2004 was studied in a population of 5119 women. RESULTS: The adjusted spinal BMD (L2-L4) changes by HT use during the entire 15-year follow-up were -4.8% for non-HT (p<0.0001), -4.2% for HT5 (p=0.003), +0.02% for HT10 (p>0.05) and +3.2% for HT15 (p<0.0001) groups. The respective femoral bone losses were -8.6% for non-HT (p<0.0001), -7.9% for HT5 (p<0.0001), -2.5% for HT10 (p=0.010) and -0.2% for HT15 (p>0.05) groups. Comparing to non-HT group the risk of wrist fracture was reduced by 33% (p=0.045) in HT10 group and by 63% (p<0.0001) in HT15 group during the 15-year follow-up. CONCLUSION: Long-term HT-use protects from bone loss. Thus, it reduces the incidence of osteopenia, osteoporosis and wrist fractures. Still, HT-use of less than 5 years did not have long-term bone protective effects, but a larger sample size is needed to confirm this result. PMID- 26857880 TI - Adverse drug reactions in elderly patients with cognitive disorders: A systematic review. AB - Elderly subjects with cognitive disorders are at particularly high risk of adverse drug reactions (ADRs). The objectives of our systematic review were to describe the prevalence of ADRs in elderly patients with cognitive disorders, the different types of ADRs and the medications suspected of involvement; to describe whether the ADRs were preventable or not, and to identify risk factors for occurrence of ADRs in this population. A bibliographic search was performed in the following databases: PubMed, Embase, Google Scholar, Opengrey and Scopus. The search included all publications up to and including 4th February 2015, with no specific start date specified. Studies concerning ADRs in elderly patients with cognitive disorders or dementia were included. Two senior authors identified eligible studies and extracted data independently. In total, 113 studies were identified by the bibliographic search, of which six full-text articles were retained and analyzed. Prevalence of ADRs ranged from 4.8 to 37%. The main ADRs reported were neurological and psychological disorders, gastro-intestinal disorders, dermatological and allergic disorders, falls, renal and urinary disorders, cardiovascular disorders, metabolic disorders and electrolyte imbalance, and hemorrhagic events. The medications most commonly suspected of involvement in the ADRs were drugs affecting the nervous system, cardiovascular drugs, anticoagulants, and painkillers. Medical prescriptions should take into account the presence of Alzheimer's disease and related syndromes. Compliance should systematically be evaluated, and cognitive disorders need to be better recognized. Therapeutic education of patients and/or their caregiver is key to management of elderly patients with cognitive disorders. PMID- 26857881 TI - Small Steps: Preliminary effectiveness and feasibility of an incremental goal setting intervention to reduce sitting time in older adults. AB - OBJECTIVE: This study aimed to evaluate the preliminary effectiveness and feasibility of a theory-informed program to reduce sitting time in older adults. DESIGN: Pre-experimental (pre-post) study. Thirty non-working adult (>= 60 years) participants attended a one hour face-to-face intervention session and were guided through: a review of their sitting time; normative feedback on sitting time; and setting goals to reduce total sitting time and bouts of prolonged sitting. Participants chose six goals and integrated one per week incrementally for six weeks. Participants received weekly phone calls. OUTCOME MEASURES: Sitting time and bouts of prolonged sitting (>= 30 min) were measured objectively for seven days (activPAL3c inclinometer) pre- and post-intervention. During these periods, a 24-h time recall instrument was administered by computer-assisted telephone interview. Participants completed a post-intervention project evaluation questionnaire. Paired t tests with sequential Bonferroni corrections and Cohen's d effect sizes were calculated for all outcomes. RESULTS: Twenty seven participants completed the assessments (71.7 +/- 6.5 years). Post intervention, objectively-measured total sitting time was significantly reduced by 51.5 min per day (p=0.006; d=-0.58) and number of bouts of prolonged sitting by 0.8 per day (p=0.002; d=-0.70). Objectively-measured standing increased by 39 min per day (p=0.006; d=0.58). Participants self-reported spending 96 min less per day sitting (p<0.001; d=-0.77) and 32 min less per day watching television (p=0.005; d=-0.59). Participants were highly satisfied with the program. CONCLUSION: The 'Small Steps' program is a feasible and promising avenue for behavioral modification to reduce sitting time in older adults. PMID- 26857882 TI - The NICE menopause guidelines. PMID- 26857883 TI - Associations between the number of natural teeth in postmenopausal women and duration of lactation: The 2010-2012 Korea National Health and Nutrition Examination Survey. AB - OBJECTIVES: Lactation is reported to be associated with changes in maternal calcium homeostasis. The relationship between lactation and long-term oral health remains to be revealed. This study was aimed to evaluate the relationship between lactation and the number of natural teeth in postmenopausal women using nationally representative data. METHODS: The data from the Korea National Health and Nutrition Examination Survey between 2010 and 2012 were used, and the analysis in this study was confined to 4211 respondents over 19 years old who had gone through menopause and had no missing values for the reproductive factors and outcome variables. The total number of natural teeth was then calculated after excluding third molars. Multiple logistic regression analyses were used to assess the associations of the number of natural teeth and lactation. RESULTS: As the duration of total lactation increased, the number of natural teeth decreased. Average duration of lactation per child showed similar trends. The association between the total duration of lactation and the number of natural teeth showed an inverse relationship with a beta value of -0.0181 per day after adjustment, and the beta value of the average duration of lactation per child was -0.0287 after the adjustment. The odds ratios of the percentage of individuals with the number of teeth <= 27 tended to increase with increased duration of lactation. Adjusted odds ratios and 95% confidence intervals were 1.830 (1.009, 3.320); 1.142 (0.765, 1.704); 1.159 (0.807, 1.664); and 0.857 (0.563, 1.306) for lactation period of >= 25 months, 13-24 months, 7-12 months, <= 6 months, and no lactation, respectively. CONCLUSIONS: This study investigated the relationship between the number of teeth and the total duration of lactation or an average duration of lactation per child using nationally representative data. Total duration of lactation and average duration of lactation per child were inversely related to the number of natural teeth. Lactation may be considered to be an independent risk indicator for tooth loss in Korean postmenopausal women. PMID- 26857884 TI - EMAS recommendations for conditions in the workplace for menopausal women. AB - Women form a large part of many workforces throughout Europe. Many will be working throughout their menopausal years. Whilst the menopause may cause no significant problems for some, for others it is known to present considerable difficulties in both their personal and working lives. During the menopausal transition women report that fatigue and difficulties with memory and concentration can have a negative impact on their working lives. Furthermore, hot flushes can be a source of embarrassment and distress. Some consider that these symptoms can impact on their performance. Greater awareness among employers, together with sensitive and flexible management can be helpful for women at this time. Particular strategies might include: fostering a culture whereby employees feel comfortable disclosing health problems, allowing flexible working, reducing sources of work-related stress, providing easy access to cold drinking water and toilets, and reviewing workplace temperature and ventilation. PMID- 26857885 TI - Subjective urinary urgency in middle age women: A population-based study. AB - AIMS: There are few population-based studies evaluating the epidemiology of overactive bladder syndrome (OAB) in women, especially in the climacteric stage where there is a decrease in estrogen production. This study aimed to assess the prevalence of OAB and associated factors in climacteric Brazilian women. METHODS: A descriptive, exploratory, cross-sectional study was conducted between September 2012 and June 2013 with 749 women (a population-based household survey). The dependent variable was OAB, defined as the presence of urinary urgency, with or without urinary incontinence, and when there was no concomitant stress urinary incontinence. The independent variables were sociodemographic data, health related habits and problems, self-perception of health, and gynecological background. Statistical analysis was carried out by Chi-square test and Poisson regression using the backward selection criteria. RESULTS: Mean age was 52.5 (+/- 4.4) years. With regard to menopausal status, 16% were premenopausal, 16% perimenopausal and 68% postmenopausal. The prevalence of OAB was 7.8%. The vast majority of women had only urinary urgency. Only two women who responded to the interview reported urge incontinence. In the final statistical model, vaginal dryness (PR 1.75; 95% CI 1.13-2.69; p=0.012) and bilateral oophorectomy (PR 2.21; 95% CI 1.11-4.40; p=0.025) were associated with a greater prevalence of OAB. CONCLUSIONS: Health professionals should adopt a proactive behavior in surgically menopausal women and those with a history of genital atrophy to identify and treat OAB, thus contributing to an improved quality of life and healthier aging. PMID- 26857886 TI - Menopause in the workplace: What employers should be doing. AB - Large numbers of women transition through menopause whilst in paid employment. Symptoms associated with menopause may cause difficulties for working women, especially if untreated, yet employers are practically silent on this potentially costly issue. This review summarises existing research on the underexplored topic of menopause in the workplace, and synthesises recommendations for employers. Longstanding scholarly interest in the relationship between employment status and symptom reporting typically (but not consistently) shows that women in paid employment (and in specific occupations) report fewer and less severe symptoms than those who are unemployed. Recent studies more systematically focused on the effects of menopausal symptoms on work are typically cross-sectional self-report surveys, with a small number of qualitative studies. Though several papers established that vasomotor (and associated) symptoms have a negative impact on women's productivity, capacity to work and work experience, this is not a uniform finding. Psychological and other somatic symptoms associated with menopause can have a relatively greater negative influence. Physical (e.g., workplace temperature and design) and psychosocial (e.g., work stress, perceptions of control/autonomy) workplace factors have been found to influence the relationship between symptoms and work. Principal recommendations for employers to best support menopausal women as part of a holistic approach to employee health and well-being include risk assessments to make suitable adjustments to the physical and psychosocial work environment, provision of information and support, and training for line managers. Limitations of prior studies, and directions for future research are presented. PMID- 26857887 TI - Resistance training for hot flushes in postmenopausal women: Randomized controlled trial protocol. AB - OBJECTIVES: Hot flushes and night sweats affect 75% of all women after menopause and is a common reason for decreased quality of life in mid-aged women. Hormone therapy is effective in ameliorating symptoms but cannot be used by all women due to contraindications and side effects. Engagement in regular exercise is associated with fewer hot flushes in observational studies, but aerobic exercise has not proven effective in randomized controlled trials. It remains to be determined whether resistance training is effective in reducing hot flushes and improves quality of life in symptomatic postmenopausal women. The aim of this study is to investigate the effect of standardized resistance training on hot flushes and other health parameters in postmenopausal women. STUDY DESIGN: This is an open, parallel-group, randomized controlled intervention study conducted in Linkoping, Sweden. Sixty symptomatic and sedentary postmenopausal women with a mean of at least four moderate to severe hot flushes per day or 28 per week will be randomized to an exercise intervention or unchanged physical activity (control group). The intervention consists of 15 weeks of standardized resistance training performed three times a week under supervision of a physiotherapist. MAIN OUTCOME MEASURES: The primary outcome is hot flush frequency assessed by self-reported hot flush diaries, and the difference in change from baseline to week 15 will be compared between the intervention group and the control group. CONCLUSION: The intention is that this trial will contribute to the evidence base regarding effective treatment for hot flushes. PMID- 26857888 TI - Effects of physical exercise during adjuvant breast cancer treatment on physical and psychosocial dimensions of cancer-related fatigue: A meta-analysis. AB - Cancer-related fatigue has a multidimensional nature and complaints typically increase during adjuvant treatment for breast cancer. Physical exercise might prevent or reduce cancer-related fatigue. So far, no meta-analysis has investigated the effects of physical exercise on different dimensions of fatigue. The aim of the present meta-analysis was to investigate the effects of physical exercise during adjuvant breast cancer treatment on physical and psychosocial dimensions of fatigue. We performed a systematic literature search in PubMed, Embase and the Cochrane Library in June 2015. Randomised controlled trials reporting the effects of physical exercise during adjuvant breast cancer treatment on different dimensions of fatigue were included. Pooled effects of 6 exercise programmes (including 784 patients) showed significant beneficial exercise effects on general fatigue (ES: -0.22, 95% CI -0.38; -0.05) and physical fatigue (ES: -0.35, 95% CI -0.49; -0.21). Effects on fatigue subscales 'reduced activity' (ES: -0.22, 95% CI -0.38; -0.05) and 'reduced motivation' (ES: -0.18, 95% CI -0.35; -0.01) were also in favour of physical exercise. No effects were found on cognitive and affective fatigue. Including only the supervised exercise programmes (n=4 studies), slightly larger pooled effect estimates were found on general fatigue (ES: -0.25, 95% CI -0.47; -0.04) and physical fatigue (-0.39, 95% CI -0.56; -0.23). In conclusion, physical exercise during adjuvant breast cancer treatment has beneficial effects on general fatigue, physical fatigue, 'reduced activity' and 'reduced motivation', but did not show effects on cognitive and affective fatigue. Largest effect sizes are found for physical fatigue, suggesting that this is the fatigue dimension most sensitive to physical exercise. PMID- 26857889 TI - Eating disorders in midlife women: A perimenopausal eating disorder? AB - Eating disorders afflict women across the lifespan with peak onset during critical or sensitive developmental periods of reproductive hormone change, such as puberty. A growing body of research supports the role of reproductive hormones, specifically estrogen, in the risk for eating disorders and related symptomatology in adolescence and young adulthood. Like puberty, perimenopause is characterized by estrogen change and may also present a window of vulnerability to eating disorder development. Here, we discuss the evidence that suggests perimenopause indeed may be a vulnerable period for the development or redevelopment of an eating disorder for midlife women. Drawing from what is known about the influence of estrogen on eating disorders at younger ages and from other psychiatric disorders with similar risk trajectories (i.e., perimenopausal depression), we describe a potential mechanism of risk for a perimenopausal eating disorder and how this can be explored in future research. Investigating vulnerability to perimenopausal eating disorders will clarify eating disorder etiology, identify reproductive stage-specific risk profiles, and guide future treatment directions. PMID- 26857890 TI - A systematic review of social support interventions for caregivers of people with dementia: Are they doing what they promise? AB - OBJECTIVE: Social support interventions for caregivers of persons with dementia (PwD) are important because informal carers often rely on their social networks for support. This systematic review synthesises findings from research on social support interventions, and examines their methodological quality and effectiveness on caregiver social support and well-being variables. METHODS: A systematic literature search utilised five databases. Papers were selected when the primary aim of the intervention was to improve social support. Quality of papers was assessed by the Level of Evidence grade and the criteria list from the Cochrane Back Review Group. RESULTS: 39 papers were identified and classified into 4 social support intervention categories: befriending and peer support, family support and social network interventions, support groups, and remote interventions using the internet or telephone. Content, intensity, uptake, effectiveness and quality of interventions varied widely. In general, the level of evidence was low. Most studies measured effect on well-being variables, while few examined social support outcomes. Multi-component social support interventions were most effective. Evidence suggested, also a caregiver benefit from remote interventions. Generally, results were inconsistent; some papers demonstrated beneficial results, while others demonstrated no improvement on social support and well-being variables. Social support outcomes were more positively evaluated when qualitative outcome measures rather than quantitative measures were used. CONCLUSIONS: Although multi-component social support interventions may improve caregiver well-being, there is insufficient evidence to conclude whether a change in social support is the underlying mediating factor. The inclusion, validation and operationalization of caregiver social support measures deserve more attention. PMID- 26857891 TI - Genetic analysis of 17 Y-STR loci in Han population from Shandong Province in East China. PMID- 26857892 TI - What products are considered psychoactive under New Zealand's legal market for new psychoactive substances (NPS, 'legal highs')? Implications for law enforcement and penalties. AB - The problem of defining what psychoactive products and substances should be covered by legislation aimed at controlling new psychoactive substances (NPS; 'legal highs') is central to the current debate on designing new legislative responses to NPS. In New Zealand, implementation of the Psychoactive Substances Act 2013 (PSA) revealed uncertainties about which psychoactive products are covered by the new regime, with important implications for legal penalties. We reviewed five pieces of legislation which can cover substances with psychoactive properties: PSA, Misuse of Drugs Act (MODA), Food Act, Dietary Supplements Regulations and Medicines Act. Our analysis revealed that a number of psychoactive substances which are not MODA-scheduled may potentially fall under more than one regulatory regime, including kava, Salvia divinorum, nitrous oxide, 25I-NBOMe, and 1,3-dimethylbutylamine (DMBA). For example, kava may be classified as a food, a dietary supplement, a herbal remedy, or a psychoactive substance, depending on how it is presented (including advertising and labelling). There are considerable differences in penalties and regulatory requirements between the different legislative regimes and these may result in unnecessary prosecutions or 'gaming' of the system. We discuss a number of ways to more clearly categorize products, including a public schedule of psychoactive substances and products, demarcation criteria based on the quantity of the active ingredient, and demarcation based on 'discernible intoxication'. Routine use of forensic testing is essential to ensure appropriate prosecutions and penalties. Robust safety standards are also required in legislative regimes exempted from psychoactive substances regime to prevent 'creative compliance'. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26857893 TI - The second report of the Nordic Pediatric Renal Transplantation Registry 1997 2012: More infant recipients and improved graft survivals. AB - The NPRTSG has collected data on pediatric KTx since 1994. The registry archives information from all centers that perform pediatric KTx in Denmark, Finland, Norway, and Sweden and has 100% coverage. The first NPRTSG report was published in 1998 and was based on data collected in the 1982?1996 period. The present report provides data on 602 pediatric KTx in the Nordic countries from 1997 to 2012. Comparison of the patient demographics and one- and three-yr graft survivals between the two time cohorts revealed no significant change in the recipient and donor demographics. The number of transplantations increased by approximately 30%, doubling the recipients below the age of two yr. The use of Tac and mycophenolate as primary immunosuppression increased from practically 0% to 50% and 40%, respectively. The one- and three-yr graft survivals improved significantly (p < 0.001), especially among the youngest recipients with transplant from DD. In these patients, the one-yr survival improved from 70% to 94.6% and the three-yr graft survival from 60% to 94.6%, respectively. The improved graft survival may be at least partly due to changes in immunosuppression strategies, but also greater experience may also be of importance. PMID- 26857894 TI - Risk assessment of Bt crops on the non-target plant-associated insects and soil organisms. AB - Transgenic plants containing Bacillus thuringiensis (Bt) genes are being cultivated worldwide to express toxic insecticidal proteins. However, the commercial utilisation of Bt crops greatly highlights biosafety issues worldwide. Therefore, assessing the risks caused by genetically modified crops prior to their commercial cultivation is a critical issue to be addressed. In agricultural biotechnology, the goal of safety assessment is not just to identify the safety of a genetically modified (GM) plant, rather to demonstrate its impact on the ecosystem. Various experimental studies have been made worldwide during the last 20 years to investigate the risks and fears associated with non-target organisms (NTOs). The NTOs include beneficial insects, natural pest controllers, rhizobacteria, growth promoting microbes, pollinators, soil dwellers, aquatic and terrestrial vertebrates, mammals and humans. To highlight all the possible risks associated with different GM events, information has been gathered from a total of 76 articles, regarding non-target plant and soil inhabiting organisms, and summarised in the form of the current review article. No significant harmful impact has been reported in any case study related to approved GM events, although critical risk assessments are still needed before commercialisation of these crops. (c) 2016 Society of Chemical Industry. PMID- 26857895 TI - Treatment of hypophosphatemic rickets in generalized arterial calcification of infancy (GACI) without worsening of vascular calcification. AB - Patients with generalized arterial calcification of infancy (GACI) develop vascular calcifications early in life. About half of them die within the first 6 months despite optimal medical care. A subset of those who survive eventually develop hypophosphatemic rickets. Since hypophosphatemia and hyperphosphaturia have been previously associated with increased survival in GACI patients, physicians often avoid phosphate repletion as treatment for rickets. As a consequence, GACI patients develop severe rachitic complications such as short stature and skeletal deformities. It appears that the recognition of hypophosphatemia later in life in some GACI patients is a consequence of having survived the first few months of life, and not the cause of their survival per se. Here, we report the long-term follow-up of a GACI patient who was phosphate repleted for his rickets for more than 7 years without worsening of vascular calcification. PMID- 26857896 TI - Newly graduated nurses' use of knowledge sources: a meta-ethnography. AB - AIM: To advance evidence on newly graduated nurses' use of knowledge sources. BACKGROUND: Clinical decisions need to be evidence-based and understanding the knowledge sources that newly graduated nurses use will inform both education and practice. Qualitative studies on newly graduated nurses' use of knowledge sources are increasing though generated from scattered healthcare contexts. Therefore, a metasynthesis of qualitative research on what knowledge sources new graduates use in decision-making was conducted. DESIGN: Meta-ethnography. DATA SOURCES: Nineteen reports, representing 17 studies, published from 2000-2014 were identified from iterative searches in relevant databases from May 2013-May 2014. REVIEW METHODS: Included reports were appraised for quality and Noblit and Hare's meta-ethnography guided the interpretation and synthesis of data. RESULTS: Newly graduated nurses' use of knowledge sources during their first 2-year postgraduation were interpreted in the main theme 'self and others as knowledge sources,' with two subthemes 'doing and following' and 'knowing and doing,' each with several elucidating categories. The metasynthesis revealed a line of argument among the report findings underscoring progression in knowledge use and perception of competence and confidence among newly graduated nurses. CONCLUSION: The transition phase, feeling of confidence and ability to use critical thinking and reflection, has a great impact on knowledge sources incorporated in clinical decisions. The synthesis accentuates that for use of newly graduated nurses' qualifications and skills in evidence-based practice, clinical practice needs to provide a supportive environment which nurtures critical thinking and questions and articulates use of multiple knowledge sources. PMID- 26857897 TI - Religiosity as a protective factor for hazardous drinking and drug use among sexual minority and heterosexual women: Findings from the National Alcohol Survey. AB - OBJECTIVE: Despite research documenting disparities in risk for alcohol-related problems among sexual minority women, few studies explore potential protective factors within this population. This study examines how religiosity may function as a protective or risk factor for alcohol-problems or other substance use among sexual minorities compared to heterosexuals. METHOD: Data from 11,169 women who responded to sexual identity and sexual behavior questions from three population based National Alcohol Survey waves (2000, 2005, 2010) were utilized for analyses of religiosity in relation to lifetime drinking, past year hazardous drinking, and past year drug use. RESULTS: Religiosity was significantly greater among exclusively heterosexual women compared to all sexual minority groups (lesbian, bisexual and heterosexual women who report same sex partners). Lesbians reported the lowest rates of affiliation with religions/denominations discouraging alcohol use. Past year hazardous drinking and use of any illicit drugs were significantly lower among exclusively heterosexual women compared to all sexual minority groups. High religiosity was associated with lifetime alcohol abstention and was found to be protective against hazardous drinking and drug use among both sexual minority and heterosexual women. Reporting religious norms unfavorable to drinking was protective against hazardous drinking among exclusively heterosexual women but not sexual minority women. CONCLUSIONS: Findings reveal the importance of considering sexual minority status in evaluation of religion or spirituality as protective among women. Future studies should explore religiosity in the context of other individual and environmental factors, such as positive identity development and community-level acceptance, which may be salient to resiliency among sexual minorities. PMID- 26857898 TI - HIV primary care providers--Screening, knowledge, attitudes and behaviors related to alcohol interventions. AB - BACKGROUND: Alcohol has particularly harmful health effects in HIV-infected patients; therefore, HIV clinics are an important setting for integration of brief alcohol intervention and alcohol pharmacotherapy to improve patient outcomes. Current practices of alcohol screening, counseling, and prescription of pharmacotherapy by HIV providers are unknown. METHODS: We conducted a cross sectional survey of HIV providers from 8 HIV clinical sites across the United States. Surveys queried knowledge and use of alcohol screening, brief advice, counseling and pharmacotherapy, confidence and willingness to prescribe pharmacotherapy and barriers to their use of alcohol pharmacotherapy. We used multivariable logistic regression to examine provider factors associated with confidence and willingness to prescribe pharmacotherapy. RESULTS: Providers (N=158) were predominantly female (58%) and Caucasian (73%); almost half were infectious disease physicians and 31% had been in practice 10-20 years. Most providers (95%) reported always or usually screening for alcohol use, although only 10% reported using a formal screening tool. Over two-thirds never or rarely treated alcohol-dependent patients with pharmacotherapy themselves. Most (71%) referred alcohol-dependent patients for treatment. Knowledge regarding alcohol pharmacotherapy was low. The major barrier to prescribing pharmacotherapy was insufficient training on use of pharmacotherapy. Provider confidence ratings were positively correlated with their practice patterns. CONCLUSIONS: HIV providers reported high rates of screening for alcohol use, though few used a formal screening tool. Most providers referred alcohol dependent patients to outside resources for treatment. Few reported prescribing alcohol pharmacotherapy. Increased training on alcohol pharmacotherapy may increase confidence in prescribing and use of these medications in HIV care settings. PMID- 26857899 TI - New Perspectives for Fixed Dose Combinations of Poorly Water-Soluble Compounds: a Case Study with Ezetimibe and Lovastatin. AB - PURPOSE: Aiming to improve the dissolution rate of ezetimibe (EZE) and lovastatin (LOV) in a fixed dose combination (FDC), co-amorphous systems and ternary solid dispersions were prepared by quench cooling and spray drying, respectively. METHODS: Formulations were characterized through X-ray diffraction, modulated differential scanning calorimetry, infrared spectroscopy, scanning electron microscopy and laser diffraction, and evaluated by 'in vitro' dissolution. Stability studies were conducted at different conditions during 30 days with the ternary solid dispersion composed of 75% of Soluplus(r) (ELS 1:1 75%). RESULTS: Single phase co-amorphous systems made up of the pure drugs were not able to increase the dissolution rate of EZE and LOV. However, ternary solid dispersions achieved high dissolution for both compounds, especially when Soluplus(r) was used as carrier. The dissolution efficiency increased up to 18 (EZE) and 6 (LOV) times in ternary solid dispersions, compared to the crystalline drugs. ELS 1:1 75% preserved its amorphous state during 30 days, in different stability conditions. CONCLUSIONS: A spray dried ternary solid dispersion able to enhance the dissolution rate of two poorly soluble, therapeutically complementary drugs, is reported for the first time. These promising results open new perspectives for the development of more advanced FDCs. PMID- 26857900 TI - Long-Acting Phospholipid Gel of Exenatide for Long-Term Therapy of Type II Diabetes. AB - PURPOSE: This study aimed to develop a sustained-release formulation of exenatide (EXT) for the long-term therapeutic efficacy in the treatment of type II diabetes. METHODS: In this study, we present an injectable phospholipid gel by mixing biocompatible phospholipid S100, medium chain triglyceride (MCT) with 85% (w/w) ethanol. A systemic pre-formulation study has been carried out to improve the stability of EXT during formulation fabrication. With the optimized formulation, the pharmacokinetic profiles in rats were studied and two diabetic animal models were employed to evaluate the therapeutic effect of EXT phospholipid gel via a single subcutaneous injection versus repeated injections of normal saline and EXT solution. RESULTS: With optimized formulation, sustained release of exenatide in vivo for over three consecutive weeks was observed after one single subcutaneous injection. Moreover, the pharmacodynamic study in two diabetic models justified that the gel formulation displayed a comparable hypoglycemic effect and controlled blood glucose level compared with exenatide solution treated group. CONCLUSIONS: EXT-loaded phospholipid gel represents a promising controlled release system for long-term therapy of type II diabetes. PMID- 26857901 TI - Involvement of Endocannabinoids in Alcohol "Binge" Drinking: Studies of Mice with Human Fatty Acid Amide Hydrolase Genetic Variation and After CB1 Receptor Antagonists. AB - BACKGROUND: The endocannabinoid system has been found to play an important role in modulating alcohol intake. Inhibition or genetic deletion of fatty acid amide hydrolase (FAAH; a key catabolic enzyme for endocannabinoids) leads to increased alcohol consumption and preference in rodent models. A common human single nucleotide polymorphism (SNP; C385A, rs324420) in the FAAH gene is associated with decreased enzymatic activity of FAAH, resulting in increased anandamide levels in both humans and FAAH C385A knock-in mice. METHODS: As this FAAH SNP has been reported to be associated with altered alcohol abuse, the present study used these genetic knock-in mice containing the human SNP C385A to determine the impact of variant FAAH gene on alcohol "binge" drinking in the drinking-in-the dark (DID) model. RESULTS: We found that the FAAH(A/A) mice had greater alcohol intake and preference than the wild-type FAAH(C/C) mice, suggesting that increased endocannabinoid signaling in FAAH(A/A) mice led to increased alcohol "binge" consumption. The specificity on alcohol vulnerability was suggested by the lack of any FAAH genotype difference on sucrose or saccharin intake. Using the "binge" DID model, we confirmed that selective CB1 receptor antagonist AM251 reduced alcohol intake in the wild-type mice. CONCLUSIONS: These data suggest that there is direct and selective involvement of the human FAAH C385A SNP and CB1 receptors in alcohol "binge" drinking. PMID- 26857903 TI - Anaphylaxis after prick-to-prick test with fish. AB - Skin prick testing is the diagnostic procedure for allergies and is considered to be safe. It is usually performed using the prick and the prick-to-prick method. Herein is described a pediatric case of anaphylaxis during prick-to-prick testing with raw fish in a patient who had consumed fish without any systemic allergic reactions beforehand, to illustrate that skin prick testing should be carefully planned and performed with caution in order to avoid potentially serious risks for the patient. PMID- 26857904 TI - Extremely Large Magnetoresistance at Low Magnetic Field by Coupling the Nonlinear Transport Effect and the Anomalous Hall Effect. AB - The anomalous Hall effect of a magnetic material is coupled to the nonlinear transport effect of a semiconductor material in a simple structure to achieve a large geometric magnetoresistance (MR) based on a diode-assisted mechanism. An extremely large MR (>10(4) %) at low magnetic fields (1 mT) is observed at room temperature. This MR device shows potential for use as a logic gate for the four basic Boolean logic operations. PMID- 26857902 TI - Equine Protozoal Myeloencephalitis: An Updated Consensus Statement with a Focus on Parasite Biology, Diagnosis, Treatment, and Prevention. AB - Equine protozoal myeloencephalitis (EPM) remains an important neurologic disease of horses. There are no pathognomonic clinical signs for the disease. Affected horses can have focal or multifocal central nervous system (CNS) disease. EPM can be difficult to diagnose antemortem. It is caused by either of 2 parasites, Sarcocystis neurona and Neospora hughesi, with much less known about N. hughesi. Although risk factors such as transport stress and breed and age correlations have been identified, biologic factors such as genetic predispositions of individual animals, and parasite-specific factors such as strain differences in virulence, remain largely undetermined. This consensus statement update presents current published knowledge of the parasite biology, host immune response, disease pathogenesis, epidemiology, and risk factors. Importantly, the statement provides recommendations for EPM diagnosis, treatment, and prevention. PMID- 26857905 TI - (124)I PET/CT in Patients with Differentiated Thyroid Cancer: Clinical and Quantitative Image Analysis. AB - BACKGROUND: Although radioactive iodine (RAI) imaging/therapy is one of the earliest applications of theranostics, there remain a number of unresolved clinical questions as to the optimization of diagnostic techniques/protocols and improvements in patient-specific treatment planning strategies. The objectives of this study were to determine the imaging characteristics and clinical feasibility of (124)I positron emission tomography/computed tomography (PET/CT) for the determination of extent of disease and evaluation of RAI kinetics in its physiologic and neoplastic distribution in patients with differentiated thyroid cancer (DTC). METHODS: The study was designed as a prospective phase II diagnostic trial of patients with confirmed DTC. Following adequate preparation, patients received 2 mCi (124)I in liquid form and sequential whole-body PET/CT imaging was performed at five time points (2-4 h, 24 +/- 6 h, 48 +/- 6 h, 72 +/- 6 h, and 96 +/- 6 h post-administration). All patients who had (124)I imaging subsequently underwent RAI treatment with (131)I, with administered activities ranging from 100 to 300 mCi. Post-treatment scans were obtained 5-7 days after RAI treatment. A by-patient and by-lesion analysis of the (124)I images was performed and compared with the post-treatment (131)I scans as well as F-18 FDG PET/CT images. Quantitative image analysis was also performed to determine the total functional volume (mL), activity per functional volume (MUCi/mL), and cumulated activity (MUCi/h) for remnants, salivary glands, and nodal metastases. RESULTS: Fifteen patients (6 women; Mage = 57 years; range 29-91 years) were enrolled into the study. Forty-six distinct lesions were identified in these 15 patients on (124)I PET/CT images, with a sensitivity of 92.5%. In addition, (124)I identified 22.5% more foci of RAI-avid lesions compared with the planar (131)I post-treatment scans. This study demonstrates different kinetic profiles for normal thyroid remnants (peaked at 24 h with mono-exponential clearance), salivary glands (peaked at 4 h with bi-exponential clearance), and metastatic lesions (protracted retention), as well as individual variations in functional volumes and thus cumulated activities. CONCLUSIONS: (124)I PET/CT is a valuable clinical imaging tool/agent, both in determining the extent of disease in the setting of metastatic DTC and in the functional volumetric and kinetic evaluation of target lesions. PMID- 26857907 TI - Catheter Ablation of Nonparoxysmal Atrial Fibrillation Using Electrophysiologically Guided Substrate Modification During Sinus Rhythm After Pulmonary Vein Isolation. AB - BACKGROUND: The high incidence of postprocedural atrial tachycardia reduces the absolute arrhythmia-free success rate of extensive ablation strategies to treat nonparoxysmal atrial fibrillation (NPAF). We hypothesized that a strategy of targeting low-voltage zones and sites with abnormal electrograms during sinus rhythm (SR-AEs) in the left atrium after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation in patients with NPAF is superior. METHODS AND RESULTS: A total of 86 consecutive patients with NPAF were enrolled in study group. After circumferential pulmonary vein isolation, cavotricuspid isthmus ablation and cardioversion to SR, high-density mapping of left atrium was performed. Areas with low-voltage zone and SR-AE were targeted for further homogenization and elimination, respectively; 78 consecutive sex- and age-matched patients with NPAF who were treated with the stepwise approach served as the historical control group. In the study group, 92% (79/86) were successfully cardioverted after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation. Among the patients converted to SR, 70% (55/79) had low-voltage zone and SR-AE and received additional ablation, whereas in 30% (24/79) without SR-AE or low-voltage zone, no further ablation was performed. During a follow-up period of >30 months, the Kaplan-Meier estimated probability to maintain SR at 24 months was 69.8% versus 51.3%. And after a single procedure, 3.5% (3/86) developed postprocedural atrial tachycardia in study group, compared with 30% (24/78) in control group (P=0.0003). CONCLUSIONS: A strategy of selective electrophysiologically guided atrial substrate modification in SR after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation is clinically more effective than the stepwise approach for NPAF ablation. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT01716143. PMID- 26857906 TI - A Single Protein Kinase A or Calmodulin Kinase II Site Does Not Control the Cardiac Pacemaker Ca2+ Clock. AB - BACKGROUND: Fight or flight heart rate (HR) increases depend on protein kinase A (PKA)- and calmodulin kinase II (CaMKII)-mediated enhancement of Ca(2+) uptake and release from sarcoplasmic reticulum (SR) in sinoatrial nodal cells (SANC). However, the impact of specific PKA and CaMKII phosphorylation sites on HR is unknown. METHODS AND RESULTS: We systematically evaluated validated PKA and CaMKII target sites on phospholamban and the ryanodine receptor using genetically modified mice. We found that knockin alanine replacement of ryanodine receptor PKA (S2808) or CaMKII (S2814) target sites failed to affect HR responses to isoproterenol or spontaneous activity in vivo or in SANC. Similarly, selective mutation of phospholamban amino acids critical for enhancing SR Ca(2+) uptake by PKA (S16) or CaMKII (T17) to alanines did not affect HR in vivo or in SANC. In contrast, CaMKII inhibition by expression of AC3-I has been shown to slow SANC rate responses to isoproterenol and decrease SR Ca(2+) content. Phospholamban deficiency rescued SR Ca(2+) content and SANC rate responses to isoproterenol in mice with AC3-I expression, suggesting that CaMKII affects HR by modulation of SR Ca(2+) content. Consistent with this, mice expressing a superinhibitory phospholamban mutant had low SR Ca(2+) content and slow HR in vivo and in SANC. CONCLUSIONS: SR Ca(2+) depletion reduces HR and SR Ca(2+) repletion restores physiological SANC rate responses, despite CaMKII inhibition. PKA and CaMKII do not affect HR by a unique target site governing SR Ca(2+) uptake or release. HR acceleration may require an SR Ca(2+) content threshold. PMID- 26857908 TI - Twenty-Seven Years Experience With Transvenous Pacemaker Implantation in Children Weighing <10 kg. AB - BACKGROUND: Epicardial pacemaker implantation is the favored approach in children weighing <10 kg in many units. The high incidence of premature failure and fractures with earlier epicardial leads led our unit to undertake transvenous pacemaker implantation in neonates and infants from 1987. To date there have been no long-term follow-up reports of what is for many a controversial strategy. METHODS AND RESULTS: Between 1987 and 2003, 37 neonates and infants-median age 6.7 months (1 day to 3 years) and median weight 4.6 kg (2.7-10 kg)-had a permanent transvenous pacing system implanted. Pacing leads were placed into the right ventricular apex/outflow tract through a subclavian vein puncture with a redundant loop in the atrium. Three patients were lost to follow-up, 4 patients died from complications of cardiac surgery, and 2 patients had their system removed. At long-term follow-up in 28 patients at a median of 17.2 (range, 11.2 27.4) years, 10 patients have a single chamber ventricular pacemaker, 14 a dual chamber pacemaker, 3 a biventricular pacemaker, and 1 has a single chamber implantable cardioverter defibrillator. Subclavian vein patency was assessed in 26 patients. The overall subclavian vein occlusion rate was 10 of 13 (77%) <5 kg and 2 of 13 (15%) >5 kg during long-term follow-up. After a median of 14.3 (range, 13.4-17.6) years of pacing, 7 patients continue with their original lead. CONCLUSIONS: Transvenous pacing in infants <10 kg results in encouraging short- and long-term clinical outcomes. Subclavian vein occlusion remains an important complication, occurring predominantly in those weighing <5 kg. PMID- 26857909 TI - Randomized Study of Persistent Atrial Fibrillation Ablation: Ablate in Sinus Rhythm Versus Ablate Complex-Fractionated Atrial Electrograms in Atrial Fibrillation. AB - BACKGROUND: Achieving long-term successful outcomes with ablation of persistent atrial fibrillation (AF) remains a clinical and procedural challenge. We aimed to assess 2 ablation strategies for persistent AF: pulmonary vein antral isolation (PVAI) in sinus rhythm after direct current cardioversion versus PVAI and ablation targeting complex-fractionated atrial electrograms while in AF. METHODS AND RESULTS: Between June 2009 and July 2013, patients with continuous persistent AF for >=3 months were prospectively randomized to either direct current cardioversion before PVAI and posterior wall/septum ablation while in sinus rhythm (group 1), versus same ablation in group 1 in addition to complex fractionated atrial electrogram ablation while in AF (group 2). The procedural profiles and clinical outcomes of the 2 strategies were compared. Ninety patients were randomized to group 1 (n=46) or group 2 (n=44). There were no differences in baseline characteristics between groups. Over 365 days of follow-up after the index procedure, 16 patients (35%) in group 1 and 13 patients (30%) in group 2 remained arrhythmia-free off antiarrhythmic medications. Over long-term follow-up (median, 867 days), arrhythmia-free survival off antiarrhythmic medications was more likely in group 1 than in group 2 in Kaplan-Meier analysis (Log Rank P=0.04). Group 1 ablation was associated with significantly shorter procedural duration and fluoroscopy time (231+/-72 versus 273+/-76 min; P=0.008 and 54 [Q1 Q3: 46-67] versus 66 (Q1-Q3: 53-83] min; P=0.018, respectively). CONCLUSIONS: In patients with persistent AF, PVAI in sinus rhythm after direct current cardioversion is associated with higher success and shorter procedural and fluoroscopy times compared with PVAI in AF with additional complex-fractionated atrial electrogram ablation. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02429648. PMID- 26857910 TI - Electrophysiologically Guided Substrate Modification During Sinus Rhythm: Personalized Approach to Nonparoxysmal Atrial Fibrillation. PMID- 26857911 TI - Pacemakers and Other Cardiac Implantable Devices in Children: Learning From Practice Variation Including Outliers in the Electronic Age. PMID- 26857913 TI - Numbers which count. PMID- 26857914 TI - NMR study of the influence of n-alkanol co-surfactants on reverse micelles in quaternary microemulsions of cetyltrimethylammonium bromide (CTAB). AB - The effects of different n-alkanol co-surfactants on the size, shape, composition and dynamics of reverse micelles (RMs) in cetyltrimethylammonium bromide (CTAB)/n alkanol/n-hexane/water and CTAB/n-alkanol/n-pentane/water microemulsions were investigated using T2 relaxation and pulsed gradient stimulated echo nuclear magnetic resonance (NMR) measurements and molecular modelling. NMR T2 relaxation times and diffusion coefficients were determined for the surfactant and co surfactant in these CTAB quaternary reverse microemulsions, for a range of medium chain length alcohol co-surfactants, from 1-butanol to 1-heptanol. These data revealed a slight RM size dependency on co-surfactant chain length, with RM sizes tending to decrease with increasing alcohol chain length. Molecular modelling of CTAB/n-alkanol/n-hexane/water RMs suggested a variation in RM shape with co surfactant chain length, where those formed with pentanol were found to be least spherical and those formed with heptanol the most spherical. The NMR data also revealed differences in the behaviour of the micellar structures in the CTAB/n pentanol/n-hexane/water reverse microemulsion, compared with the other reverse microemulsions in this study, where CTAB was found to be distributed between two environments, which then combined to form larger micelles. The origins of these differences remain unclear. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26857912 TI - Neurogenic Niche Microglia Undergo Positional Remodeling and Progressive Activation Contributing to Age-Associated Reductions in Neurogenesis. AB - Neural stem cells (NSCs) exist throughout life in the ventricular-subventricular zone (V-SVZ) of the mammalian forebrain. During aging NSC function is diminished through an unclear mechanism. In this study, we establish microglia, the immune cells of the brain, as integral niche cells within the V-SVZ that undergo age associated repositioning in the V-SVZ. Microglia become activated early before NSC deficits during aging resulting in an antineurogenic microenvironment due to increased inflammatory cytokine secretion. These age-associated changes were not observed in non-neurogenic brain regions, suggesting V-SVZ microglia are specialized. Using a sustained inflammatory model in young adult mice, we induced microglia activation and inflammation that was accompanied by reduced NSC proliferation in the V-SVZ. Furthermore, in vitro studies revealed secreted factors from activated microglia reduced proliferation and neuron production compared to secreted factors from resting microglia. Our results suggest that age associated chronic inflammation contributes to declines in NSC function within the aging neurogenic niche. PMID- 26857915 TI - Malaria vectors and their blood-meal sources in an area of high bed net ownership in the western Kenya highlands. AB - BACKGROUND: Blood-meal sources of malaria vectors affect their capacity to transmit the disease. Most efficient malaria vectors prefer human hosts. However, with increasing personal protection measures it becomes more difficult for them to find human hosts. Here recent malaria vector blood-meal sources in western Kenya highlands were investigated. METHODS: Adult mosquitoes resting indoors, outdoors and exiting through windows were collected in three study areas within the western Kenya highlands from June 2011 to June 2013. A census of people, livestock and of insecticide-treated nets was done per house. Mosquito blood-meal sources were determined as human, goat, bovine or chicken using enzyme-linked immunosorbent assays. RESULTS: Most (86.3 %) households possessed at least one bed net, 57.2 % had domesticated animals and 83.6 % had people sharing houses with livestock at night. Most (94.9 %) unfed malaria vectors were caught exiting through windows. Overall, 53.1 % of Anopheles gambiae sensu stricto obtained blood-meals from humans, 26.5 % from goats and 18.4 % from bovines. Single blood meal sources by An. gambiae s.s. from humans were 26.5 %, 8.2 % from bovines and 2.0 % from goats. Mixed blood-meal sources by An. gambiae s.s. identified included: 24.5 % human/goat, 10.2 % human/bovine, 8.2 % human/bovine/goat and also 8.2 % bovine/goat. One An. arabiensis mosquito obtained blood-meal only from humans. CONCLUSION: An unusually high frequency of animal and mixed human-animal blood meals in the major malaria vector An. gambiae s.s. was revealed in the western Kenya highlands where bed net coverage is above the WHO target. The shift in blood-meal sources from humans to livestock is most likely the vectors' response to increased bed net coverage and the close location of livestock frequently in the same house as people at night. Livestock-targeted interventions should be considered under these circumstances to address residual malaria transmission. PMID- 26857916 TI - Small RNA and degradome deep sequencing reveals drought-and tissue-specific micrornas and their important roles in drought-sensitive and drought-tolerant tomato genotypes. AB - Drought stress has adverse impacts on plant production and productivity. MicroRNAs (miRNAs) are one class of noncoding RNAs regulating gene expression post-transcriptionally. In this study, we employed small RNA and degradome sequencing to systematically investigate the tissue-specific miRNAs responsible to drought stress, which are understudied in tomato. For this purpose, root and upground tissues of two different drought-responsive tomato genotypes (Lycopersicon esculentum as sensitive and L. esculentum var. cerasiforme as tolerant) were subjected to stress with 5% polyethylene glycol for 7 days. A total of 699 conserved miRNAs belonging to 578 families were determined and 688 miRNAs were significantly differentially expressed between different treatments, tissues and genotypes. Using degradome sequencing, 44 target genes were identified associated with 36 miRNA families. Drought-related miRNAs and their targets were enriched functionally by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Totally, 53 miRNAs targeted 23 key drought stress- and tissue development-related genes, including DRP (dehydration responsive protein), GTs (glycosyltransferases), ERF (ethylene responsive factor), PSII (photosystem II) protein, HD-ZIP (homeodomain-leucine zipper), MYB and NAC-domain transcription factors. miR160, miR165, miR166, miR171, miR398, miR408, miR827, miR9472, miR9476 and miR9552 were the key miRNAs functioning in regulation of these genes and involving in tomato response to drought stress. Additionally, plant hormone signal transduction pathway genes were differentially regulated by miR169, miR172, miR393, miR5641, miR5658 and miR7997 in both tissues of both sensitive and tolerant genotypes. These results provide new insight into the regulatory role of miRNAs in drought response with plant hormone signal transduction and drought-tolerant tomato breeding. PMID- 26857917 TI - Ecological momentary assessment of working memory under conditions of simultaneous marijuana and tobacco use. AB - BACKGROUND AND AIMS: The neuropsychological correlates of simultaneous marijuana and tobacco use are largely unknown, which is surprising as both substances have similar neural substrates and have opposing influences on working memory (WM). This study examined the effects of marijuana alone, tobacco alone and simultaneous marijuana and tobacco use on WM. DESIGN: Primary aims were tested using a within-subject design, controlling for multiple subject- and momentary level confounds via ecological momentary assessment (EMA). SETTING: Data collection occurred in the Chicago, USA area in participants' natural environments. PARTICIPANTS: Participants were 287 community young adults from a larger natural history study, oversampled for ever smoking, all of whom event recorded at least one substance use occasion during the study week. MEASUREMENTS: Momentary tobacco, marijuana and alcohol use were recorded during multiple EMA across 1 week of data capture. WM was assessed at the end of each EMA assessment. Contextual variables that may influence WM were recorded via EMA. FINDINGS: There were main effects for marijuana and tobacco: WM was poorer with marijuana [odds ratio (OR) = 0.91, 95% confidence interval (CI) = 0.84-0.99] and better with tobacco (OR = 1.11, 95% CI = 1.04-1.18). These effects were not qualified by an interaction (OR = 1.03, 95% CI = 0.84-1.26). Alcohol also reduced WM (OR = 0.87, 95% CI = 0.79-0.95), and the tobacco * alcohol interaction was significant (OR = 0.81, 95% CI = 0.66-0.99), indicating that the facilitative effect of tobacco disappeared with concurrent alcohol use. CONCLUSIONS: Relative to when individuals did not use these substances, working memory decreased with acute marijuana and alcohol use and increased with acute tobacco use. However, the putative effect of marijuana on working memory and the facilitative effect of tobacco on working memory were no longer present when used simultaneously with tobacco and alcohol, respectively. Data suggest that tobacco use may compensate for working memory decrements from marijuana among young adults and highlight the importance of investigating further the negative impact of alcohol use on cognition. PMID- 26857918 TI - Erratum to: Does percutaneous dilatational tracheostomy increase the incidence of sternal wound infection--a single center retrospective of 4100 cases. PMID- 26857919 TI - Epidemiological pathology of Tau in the ageing brain: application of staging for neuropil threads (BrainNet Europe protocol) to the MRC cognitive function and ageing brain study. AB - INTRODUCTION: Deposition of abnormally phosphorylated tau (phospho-tau) occurs in Alzheimer's disease but also with brain ageing. The Braak staging scheme focused on neurofibrillary tangles, but abundant p-tau is also present in neuropil threads, and a recent scheme has been proposed by the BrainNet Europe consortium for staging tau pathology based on neuropil threads. We determined the relationship of threads to tangles, and the value of staging for threads in an unselected population-representative ageing brain cohort. We also determined the prevalence of astroglial tau pathologies, and their relationship to neuronal tau. Phospho-tau pathology was determined by immunohistochemistry (AT8 antibody) in the MRC-CFAS neuropathology cohort. Neuropil threads were staged using the BrainNet Europe protocol for tau pathology, and compared with Braak tangle stages. Astroglial tau pathology was assessed in neo-cortical, mesial temporal and subcortical areas. RESULTS: Cases conformed well to the hierarchical neuropil threads staging of the BrainNet Europe protocol and correlated strongly with Braak staging (r=0.84, p < 0.001). Based on the areas under the receiver operator curves (AUC), incorporating either threads or tangle staging significantly improved dementia case identification to a similar degree over age alone (Braak stage X (2)(1)=10.1, p=0.002; BNE stage X (2)(1)=9.7, p=0.002). Thorn-shaped astrocytes, present in 40 % of cases, were most common in mesial temporal lobe, then brainstem, and were associated with subpial tau-positive neurites (mesial temporal: X (2)(1)=61.3, p < 0.001; brainstem: X (2)(1)=47.9, p < 0.001). Adding thorn astrocytes did not improve dementia prediction (AUC: X (2)(1)=0.77, p=0.381), but there was a weak relationship between numbers of areas involved and staging for threads or tangles (r=0.17, p=0.023). Neuropil threads develop hierarchically in parallel with neurofibrillary tangles. CONCLUSIONS: The BrainNet Europe staging protocol is straightforward to apply, and offers similar predictive value for dementia to Braak tangle staging. Astroglial tauopathy, particularly thorn shaped astrocyte formation, does not relate to dementia status, but the association with phospho-tau neurites may suggest a pathogenic relationship to neuronal tau pathology. PMID- 26857920 TI - Resequencing and assembly of seven complex loci to improve the Leishmania major (Friedlin strain) reference genome. AB - BACKGROUND: Leishmania parasites cause severe human diseases known as leishmaniasis. These eukaryotic microorganisms possess an atypical chromosomal architecture and the regulation of gene expression occurs almost exclusively at post-transcriptional levels. Accordingly, sequencing of the genome of Leishmania major, and subsequently the genome of other related species, was paramount for highlighting these peculiar molecular aspects. Recently, we carried out an analysis of gene expression by massive sequencing of RNA in the L. major promastigote, and data derived from that analysis were suggestive of possible errors in the current genome assembly for this Leishmania species. RESULTS: During the analysis by RNA-Seq of the transcriptome for L. major Friedlin strain, 163,714 reads could not be aligned with the reference genome. Thus, de novo assembly with these reads was carried out and the resulting contigs were further analyzed. After detailed homology searches using available databases, it was postulated that 15 contigs might correspond to genomic sequences lost during the initial genome assembly of the L. major Friedlin strain. This was experimentally confirmed by PCR amplification, cloning and sequencing of the new genomic regions. As a result, we have identified seven regions of the L. major (Friedlin) genome that were lost during the sequence assembly. This led to the uncovering of six new genes (LmjF.15.1475, LmjF.15.0285, LmjF.24.0765, LmjF.14.0860, LmjF.19.0305, and LmjF.27.2035), and correction of the annotation for two others (LmjF.15.1480 and LmjF.27.2030). Our data suggest that these genomic regions probably collapsed during the genome assembly due to the existence of gene duplications and/or repeated regions surrounding the missed genes. CONCLUSION: RNA-seq data helped to reconstruct some genomic regions misassembled during the L. major Friedlin genome assembly, which is otherwise quite robust. On the other hand, this study shows that data derived from massive sequencing approaches, including RNA-Seq, should be carefully inspected to improve current genome definition and gene annotations. PMID- 26857921 TI - A voluntary deductible in health insurance: the more years you opt for it, the lower your premium? AB - Adverse selection regarding a voluntary deductible (VD) in health insurance implies that insured only opt for a VD if they expect no (or few) healthcare expenses. This paper investigates two potential strategies to reduce adverse selection: (1) differentiating the premium to the duration of the contract for which the VD holds (ex-ante approach) and (2) differentiating the premium to the number of years for which insured have opted for a VD (ex-post approach). It can be hypothesized that premiums will decrease with the duration of the contract or the number of years for which insured have opted for a VD, providing an incentive to insured to opt for a deductible also in (incidental) years they expect relatively high expenses. To test this hypothesis, we examine which premium patterns would occur under these strategies using data on healthcare expenses and risk characteristics of over 750,000 insured from 6 years. Our results show that, under the assumptions made, only without risk equalization the premiums could decrease with the duration of the contract or the number of years for which insured have opted for a VD. With (sophisticated) risk equalization, decreasing premiums seem unfeasible, both under the ex-ante and ex-post approach. Given these findings, we are sceptical about the feasibility of these strategies to counteract adverse selection. PMID- 26857922 TI - Disinhibited Attachment Disorder in UK Adopted Children During Middle Childhood: Prevalence, Validity and Possible Developmental Origin. AB - We investigate the prevalence, specificity and possible aetiology of Disinhibited Attachment Disorder (DAD) in adopted children without a history of institutional care. Sixty children adopted from UK out-of-home care (AD; mean age 102 months, 45 % male); 26 clinic-referred children with externalizing disorder (ED; mean age 104 months, 77 % male) but no history of maltreatment or disrupted care; and 55 matched low-risk comparison controls (LR; mean age 108 months, 49 % male) were assessed for DAD using a triangulation of parent, teacher, and research observations. Maltreatment history and child psychiatric symptoms were obtained from parent report and child language development was assessed. DAD was identified in 49 % of AD, 4 % of ED and 6 % of LR children. Seventy-two percent of AD children had suffered maltreatment. DAD was not associated with degree of risk exposure, demographics, or language. A significant association with ADHD did not explain variance in DAD prevalence across groups. DAD was significantly more common in children first admitted to out-of-home care between 7 and 24 months, independent of maltreatment severity, age at adoption and number of care placements. Implications for developmental theory, adoption policy and clinical application are discussed. PMID- 26857923 TI - Preparation and evaluation of valsartan by a novel semi-solid self microemulsifying delivery system using Gelucire 44/14. AB - The aim of the present study was to develop a novel semi-solid self microemulsifying drug delivery system (SMEDDS) using Gelucire((r)) 44/14 as oil with strong solid character to improve the oral bioavailability of poorly soluble drug valsartan. The solubility of valsartan in various excipients was determined, the pseudo-ternary phase diagram was constructed in order to screen the optimal excipients, and DSC analysis was performed to evaluate the melting point of SMEDDS. The optimal drug-loaded SMEDDS formulation was consisted of 30% Gelucire((r)) 44/14 (oil), 40% Solutol((r)) HS 15 (surfactant), and 30% Transcutol((r)) P (cosurfactant) (w/w) with 80 mg valsartan/g excipients. The average droplet sizes of the optimized blank and drug-loaded SMEDDS formulations were 26.20 +/- 1.43 and 33.34 +/- 2.15 nm, and the melting points of them were 35.6 and 36.8 degrees C, respectively. The in vitro dissolution rate of optimal semi-solid SMEDDS was increased compared with commercial capsules, resulting in the 2.72-fold and 2.97-fold enhancement of Cmax and AUC0-t after oral administration in rats, respectively. These results indicated that the novel semi solid SMEDDS formulation could potentially improve the oral bioavailability of valsartan, and the semi-solid SMEDDS was a desirable system than the traditional liquid SMEDDS because it was convenient for preparation, storage and transportation due to semi-solid state at room temperature and melted state at body temperature. PMID- 26857925 TI - The association of psychosocial screening and service provision in pediatric oncology: the Psychosocial Assessment Tool (PAT2.0) into clinical practice. AB - PURPOSE: Distress screening in oncology has been widely endorsed in recent years. However, current knowledge of the impact of screening on delivery of clinical psychosocial services is limited. This study investigated the association between screening and psychosocial services in the early period following diagnosis of childhood cancer. METHODS: The Psychosocial Assessment Tool (PAT2.0) was administered by clinical social workers in two pediatric oncology centers shortly following diagnosis. Psychosocial service activity in the first 8 weeks post diagnosis was collected via social work surveys and extraction of information from hospital databases. RESULTS: PAT2.0 and psychosocial service data were obtained for 89 families with a child newly diagnosed with cancer. Distribution of PAT2.0 risk categories was consistent with previous studies (57.3 % universal, 38.2 % targeted, 4.5 % clinical). Significant, weak to moderate correlations between PAT2.0 and social workers' estimates of psychosocial risk were observed. No significant differences in the amount of psychosocial services provided to families with "universal" versus "elevated" (i.e., targeted or clinical) risk were found. Number of days in hospital was strongly and positively associated with the amount of psychosocial services families received in the first 8 weeks following diagnosis. CONCLUSIONS: Psychosocial risk, as measured by the PAT2.0, and allocation of psychosocial services were not significantly associated in the early period following diagnosis. Further investigation is required to understand if differences emerge over time when psychosocial screening is implemented clinically. Development of clinical pathways of care needs to account for patients who may predominantly be treated in the outpatient setting. PMID- 26857924 TI - A randomized phase 3 study on the optimization of the combination of bevacizumab with FOLFOX/OXXEL in the treatment of patients with metastatic colorectal cancer OBELICS (Optimization of BEvacizumab scheduLIng within Chemotherapy Scheme). AB - BACKGROUND: Despite the improvements in diagnosis and treatment, colorectal cancer (CRC) is the second cause of cancer deaths in both sexes. Therefore, research in this field remains of great interest. The approval of bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in combination with a fluoropyrimidine-based chemotherapy in the treatment of metastatic CRC has changed the oncology practice in this disease. However, the efficacy of bevacizumab-based treatment, has thus far been rather modest. Efforts are ongoing to understand the better way to combine bevacizumab and chemotherapy, and to identify valid predictive biomarkers of benefit to avoid unnecessary and costly therapy to nonresponder patients. The BRANCH study in high-risk locally advanced rectal cancer patients showed that varying bevacizumab schedule may impact on the feasibility and efficacy of chemo-radiotherapy. METHODS/DESIGN: OBELICS is a multicentre, open-label, randomised phase 3 trial comparing in mCRC patients two treatment arms (1:1): standard concomitant administration of bevacizumab with chemotherapy (mFOLFOX/OXXEL regimen) vs experimental sequential bevacizumab given 4 days before chemotherapy, as first or second treatment line. Primary end point is the objective response rate (ORR) measured according to RECIST criteria. A sample size of 230 patients was calculated allowing reliable assessment in all plausible first-second line case-mix conditions, with a 80% statistical power and 2-sided alpha error of 0.05. Secondary endpoints are progression free-survival (PFS), overall survival (OS), toxicity and quality of life. The evaluation of the potential predictive role of several circulating biomarkers (circulating endothelial cells and progenitors, VEGF and VEGF-R SNPs, cytokines, microRNAs, free circulating DNA) as well as the value of the early [(18)F]-Fluorodeoxyglucose positron emission tomography (FDG-PET) response, are the objectives of the traslational project. DISCUSSION: Overall this study could optimize bevacizumab scheduling in combination with chemotherapy in mCRC patients. Moreover, correlative studies could improve the knowledge of the mechanisms by which bevacizumab enhance chemotherapy effect and could identify early predictors of response. EudraCT Number: 2011-004997-27 TRIAL REGISTRATION: ClinicalTrials.gove number, NCT01718873. PMID- 26857927 TI - Evidences for diabetes and insulin mimetic activity of medicinal plants: Present status and future prospects. AB - Diabetes mellitus (DM) is a considerable systemic metabolic disorder to exhibit various metabolic and cardiovascular disorders, mainly hyperglycemia. The global projected estimate of diabetes in 2030 will be about 439 million adults, out of which 300 million expected are of type-2 diabetes mellitus (T2DM). The present knowledge revealed responsible factors, occurrence and mechanism of these factors involved in the DM diseases. Hence, the aim of this review is to address and summarize the causes, plant resources, importance, present status and future programmes for diabetes control. The present review answers the contemporary present questions raised in the scientific field on DM. Two major problems are explained in detail about the autoimmune attack or dysfunction of beta-cell and insulin resistance involved for Type 1 and Type 2 DM, respectively. Though there are various approaches to reduce the ill effects of diabetes and its secondary complications, many preferred herbal formulations due to lesser side effects and low cost. For this reason still it is getting increased attention in searching antidiabetic medicinal plants for hot research and to develop targeted medicine. Recurrence of islet autoimmunity lesson from pancreatic islet cell transplantation to cure T1D was outlined. With these highlights, the review summarizes the current knowledge on diabetes occurrence, factors (environmental and genetics), and types (I, II, gestation, and secondary DM), antidiabetic plants, sources for insulin mimetic plant principle compounds and their target mechanism with current and future trusted research areas for controlling of DM. PMID- 26857926 TI - Genomics of gallbladder cancer: the case for biomarker-driven clinical trial design. AB - BACKGROUND AND AIMS: Gallbladder carcinoma is a rare, aggressive malignancy of the biliary tract associated with a poor prognosis. Despite the deployment of targeted therapies that have demonstrated marked survival benefits in many tumor types, traditional cytotoxic chemotherapy has remained the mainstay of treatment for unresectable and metastatic gallbladder cancer. METHODS: Systematic review of ongoing and prior clinical studies shows a paucity of biomarker-driven therapeutic trials using targeted agents in gallbladder cancer. In fact, over the past 6 years, of the 38 therapeutic biliary tract protocols listed on clinicaltrials.gov, only 6 (21 %) utilized targeted therapies based upon tumor biomarkers or genomics. Now that we have entered the era of next-generation sequencing and precision medicine, we are beginning to identify common and specific genetic alterations in gallbladder carcinomas. RESULTS: A review of the literature reveals alterations in ARID1A, BRAF, CDKN2A/B, EGFR, ERBB2-4, HKN-RAS, PIK3CA, PBRM1, and TP53. Given the widespread use of tumor genomic profiling and the fact that most of the aforementioned alterations are pharmacologically tractable, these observations suggest the potential for new therapeutic strategies in this aggressive malignancy. CONCLUSIONS: Taken together, further understanding of the genomic landscape of gallbladder cancer coupled with biomarker-driven clinical trials that match therapies to targets are urgently needed. PMID- 26857929 TI - Health outcomes of neonates with osteogenesis imperfecta: a cross-sectional study. AB - OBJECTIVE: To assess at-birth health outcomes of neonates with osteogenesis imperfecta (OI). STUDY DESIGN: A total of 53 women who self-reported having had at least one child with OI completed the survey. We evaluated pregnancy length, neonatal intensive care unit (NICU) usage, at-birth complications, and the child's clinical information including OI type, height and weight. RESULTS: Information was gathered on a total of 77 children (60 type I, 4 type III and 13 type IV). Health conditions reported at birth included breech presentation (24%), prematurity (27%), fracture (18%), bone deformity (18%) and respiratory problems (22%). Approximately 31% (n = 24) received NICU care. There was a significant association between younger maternal age, preterm delivery and NICU admission. CONCLUSION: Our findings suggest that newborns with OI appear to be at high risk of skeletal disorders, preterm delivery and breech presentation. Younger maternal age and preterm delivery seem to be strong predictors of the need for NICU care. Our data suggest that pregnant women with OI younger than 20 years of age may benefit from added clinical supervision in anticipation of adverse effects on their child. PMID- 26857928 TI - Comparing clinical outcomes for a twelve-month trial of zotarolimus- and everolimus-eluting stents in patients with coronary artery disease: data from the THCRIC registry. AB - OBJECTIVES: New-generation coronary stents including zotarolimus- and everolimus eluting stents (ZES and EES) have been shown to decrease the risk of restenosis. The purpose of this study was to compare the safety and efficacy of ZES and EES over a 12-month clinical follow up, in routine clinical practice. METHODS: This is an observational study in which 1029 consecutive patients treated with ZES (n = 669) or EES (n = 360) were enrolled. The study endpoint was major adverse cardiac events (MACE), defined as cardiac death, nonfatal myocardial infarction (MI), and target lesion or vessel revascularization at 12 months. RESULTS: Follow up was completed among 94.9% of the patients. The overall MACE occurred in 4 (0.6%) and 7 (2.0%) patients in the ZES and EES group, respectively. The occurrence of other cardiac events including nonfatal MI and target vessel or lesion revascularization was 1 (0.2%) versus 1 (0.3%) and 7 (1.1%) versus 5 (1.4%), respectively, in the ZES and EES groups of patients. Despite a slightly lower rate of MACE and cardiac death in the ZES group, the difference between these two groups was not significant (n = 0.064 for overall MACE, p = 0.129 for cardiac mortality, n = 0.999 for nonfatal MI, n = 0.468 for target vessel and n = 0.999 for target lesion revascularization). CONCLUSIONS: According to our results, it could be concluded that the difference in the rate of MACE between the ZES and EES groups was not statistically significant at 12-month follow up. PMID- 26857930 TI - Effect of providing feedback and prescribing education on prescription writing: An intervention study. AB - BACKGROUND/OBJECTIVE: Accurate medication prescribing important to avoid errors and ensure best possible outcomes. This is a report of assessment of the impact of providing feedback and educational intervention on prescribing error types and rates in routine practice. METHODS: Doctors' prescriptions from selected wards in two tertiary hospitals in central Nigeria were prospectively reviewed for a 6 month period and assessed for errors; grouped into six categories. Intervention was by providing feedback and educational outreach on the specialty/departmental level at one hospital while the other acted as the control. Chi-squared statistics was used to compare prescribing characteristics pre- and post intervention. RESULTS: At baseline, error rate was higher at the control site. At the intervention site, statistically significant reductions were obtained for errors involving omission of route of administration (P < 0.001), under dose (P = 0.012), dose adjustment in renal impairment (P = 0.019), ambiguous orders (P < 0.001) and drug/drug interaction (P < 0.001) post intervention though there was no change in mean error rate post intervention (P = 0.984). Though House Officers and Registrars wrote most prescriptions, highest reduction in prescribing error rates post intervention was by the registrars (0.93% to 0.29%, P < 0.001). CONCLUSION: Writing prescriptions that lacked essential details was common. Intervention resulted in modest changes. Routinely providing feedback and continuing prescriber education will likely sustain error reduction. PMID- 26857931 TI - Gender dimensions to the Ebola outbreak in Nigeria. AB - BACKGROUND: An outbreak of Ebola disease was declared in Lagos, South West Nigeria, on 23rd July 2014. Later, the outbreak spread to the south south and south eastern part of the country. The last cases occurred on August 31, 2014 and the country was certified to be Ebola free on 20th October, 2014. This paper describes the experiences and implications of the Ebola outbreak for Nigerian women. SUBJECTS AND METHODS: Identification and listing of cases and contacts was done in Lagos, Port Harcourt and Enugu. Socio demographic information was collected. RESULTS: Women made up 55% of Ebola cases and 56.6% of contacts traced. Of the 8 deaths reported 50.0% (4) were women, of which 75.0% (3) were health care providers. The sex specific case attack and fatality rates for males and females were 2.2% versus 2.3% and 45.5% versus 33.3% respectively. The women restricted their movement in order to avoid the infection. The outbreak affected their utilisation of health care services and livelihood. CONCLUSION: Women were exposed occupationally and domestically due to their care giving roles. In health facilities, they were directly involved in the care or encountered persons who had been in contact with persons with Ebola. In the homes, they were at the forefront of nursing the sick. There is the need to ensure women have access to information, services and personal protective equipment to enable them protect themselves from infection. Education and engagement of women is crucial to protect women from infection and for prompt outbreak containment. PMID- 26857932 TI - Relationship between serum leptin and insulin resistance among obese Nigerian women. AB - BACKGROUND: Leptin is a hormone produced directly from adipocytes and has been associated with type 2 diabetes mellitus (T2DM) which is characterized by insulin resistance (IR). Due to the increasing prevalence of obesity in sub-Saharan Africa, serum leptin can be explored as a predictive risk factor for T2DM. Therefore, the aim of this study was to determine the relationship between serum leptin and IR among obese women. METHODS: This was a cross-sectional study of obese, adult Nigerian females. Participants with body mass index (BMI) >=30 kg/m2 and nondiabetic were recruited as subjects. Fasting serum leptin, insulin, and plasma glucose were determined. IR was calculated using the formula: Homeostatic model assessment-IR (HOMA-IR) = (glucose * insulin)/22.5. Statistical analyses were performed using SPSS and P < 0.05 was considered to be significant. RESULTS: Eighty obese females with mean +/- standard deviation BMI 39.1 +/- 7.2 kg/m2 and serum leptin level 48.4 +/- 24.4 ng/ml participated in study. Prevalence of hyperleptinemia was 92.5% (confidence interval: 87.3-97.7%). The relationship between leptin and HOMA-IR among the subjects was: BMI 30-34.9 kg/m2: n = 27, r = 0.18, P = 0.42; BMI 35-39.9 kg/m2: n = 24, r = 0.36, P = 0.11; BMI >= 40 kg/m2: n = 29, r = 0.52, P = 0.004*; and after controlling for BMI (n = 29, r = 0.46, P = 0.014*). Multiple linear regression showed that leptin did not predict for IR (P = 0.837). CONCLUSION: Serum leptin levels were positively correlated with IR, which was significant among the Class III (morbid) obesity class. However, leptin was not a predictive factor for IR in obese Nigerian women. PMID- 26857933 TI - Seroprevalence of hepatitis B virus serological markers among pregnant Nigerian women. AB - BACKGROUND: Chronic hepatitis B infection is a global problem; however, Asia and sub-Saharan Africa are most affected by it. Hepatitis B status of pregnant women is essential for the effective management of the disease and prevention of mother to child transmission. MATERIALS AND METHODS: The study was conducted at the antenatal care unit of four hospitals within Kaduna Metropolis, Nigeria, between August and December 2011. After obtaining ethical clearance, blood samples were collected from 800 consenting pregnant women, the plasma were screened for hepatitis B surface antigen (HBsAg) using first response HBsAg card and the reactive sera were confirmed with enzyme-linked immunosorbent assay. Other serological markers of hepatitis B virus (HBV) were detected using the one-step HBV multi-5 test kit. RESULTS: Of the 800 pregnant women screened, 31 (3.9%) tested positive for HBsAg. Only one of the 31 HBsAg positive women had developed the hepatitis B surface antibody, 16 (51.6%) had the envelop antibody, 18 (58.1%) had the hepatitis B core antibody (anti-HBc), and two (6.5%) had hepatitis B envelop antigen (HBeAg). The highest prevalence of HBsAg was recorded among women in age group 21-25 years old (P = 0.968). Similarly, married women (P = 0.772), women in their second trimester of pregnancy (P = 0.938), women with tertiary education (P = 0.972), women from the South-East geopolitical zone (P = 0.250) and those whose husbands were in polygamous relationships (P = 0.944) had the highest seroprevalence of HBsAg. CONCLUSION: HBV was detected with a prevalence of 3.9% among pregnant women in Kaduna Metropolis, Nigeria. About 96.8% (29) of the reactive women had HBeAg negative chronic hepatitis while 6.5% (2) had HBeAg positive chronic hepatitis B infection. About 58.1% of the women had anti-HBc, hence, did not have immunity and probably had chronic infection with reduced risk of vertical transmission. Pregnant women should be screened for HBsAg at the first antenatal clinic visit for appropriate clinical management and effective prevention of vertical transmission. PMID- 26857934 TI - Nurses' knowledge of care of chest drain: A survey in a Nigerian semiurban university hospital. AB - BACKGROUND/OBJECTIVE: Inefficient nursing care of chest drains may associated with unacceptable and sometimes life-threatening complications. This report aims to ascertain the level of knowledge of care of chest drains among nurses working in wards in a teaching hospital in Nigeria. METHODS: A cross-sectional study among nurses at teaching hospital using pretested self-administered questionnaires. RESULTS: The majority were respondents aged between 31 and 40 years (45.4%) and those who have nursing experience between 6 and 10 years. Only 37 respondents (26.2%) had a good knowledge of nursing care of chest drains. Knowledge was relatively higher among nurses who cared for chest drains daily, nurses who have a work experience of <10 years, low-rank nurses and those working in the female medical ward; however, the relationship were not statistically significant (P > 0.05). Performance was poor on the questions on position of drainage system were not statistically significant with relationship to waist level while mobilizing the patient, application of suction to chest drains, daily changing of dressing over chest drain insertion site, milking of tubes and drainage system with dependent loop. CONCLUSION: The knowledge of care of chest drains among nurses is poor, especially in the key post procedural care. There is an urgent need to train them so as to improve the nursing care of patients managed with chest drains. PMID- 26857935 TI - Knowledge and practices of infection control among healthcare workers in a Tertiary Referral Center in North-Western Nigeria. AB - BACKGROUND: Healthcare acquired infections (HCAIs) otherwise call nosocomial infection is associated with increased morbidity and mortality among hospitalized patients and predisposes healthcare workers (HCWs) to an increased risk of infections. The study explores the knowledge and practices of infection control among HCW in a tertiary referral center in North-Western Nigeria. MATERIALS AND METHODS: This is a cross-sectional study. A self-administered structured questionnaire was distributed to the study group (of doctors and nurses). Data on knowledge and practice of infection control were obtained and analyzed. Study population were selected by convenience sampling. RESULTS: A total of 200 responses were analyzed, 152 were nurses while 48 were doctors. The median age and years of working experience of the respondents were 35 years (interquartile range [IQR] 31-39) and 7 years (IQR 4-12), respectively. Most of the respondents 174/198 (87.9%) correctly identified hand washing as the most effective method to prevent HCAI, with nurses having better knowledge 139/152 (91%) (P = 0.001). Majority agreed that avoiding injury with sharps 172/200 (86%), use of barrier precaution 180/200 (90%) and hand hygiene 184/200 (92%) effectively prevent HCAI. Only 88/198 (44.4%), 122/198 (61.6%), and 84/198 (42.4%) of the respondents were aware of the risks of infection following exposure to human immunodeficiency virus, hepatitis B virus and hepatitis C virus-infected blood, respectively. About 52% of doctors and 76% of nurses (P = 0.002) always practice hand hygiene in between patient care. CONCLUSION: Gaps have been identified in knowledge and practice of infection control among doctors' and nurses' in the study; hence, it will be beneficial for all HCW to receive formal and periodic refresher trainings. PMID- 26857936 TI - Acute kidney injury following multiple bee stings. PMID- 26857937 TI - The 2015 measles outbreak in America: Identified shortcomings and recommendations to the health authorities. PMID- 26857938 TI - Matching in hospital based case-control studies. PMID- 26857939 TI - Lanthanum and Neodymium Doped Barium Ferrite-TiO2/MCNTs/poly(3-methyl thiophene) Composites with Nest Structures: Preparation, Characterization and Electromagnetic Microwave Absorption Properties. AB - We report herein the synthesis of a novel nest structured electromagnetic composite through in-situ chemical polymerization of 3-methyl thiophene (3MT) in the presence of the BaFe11.92(LaNd)0.04O19-TiO2 (BFTO) nanoparticles and MCNTs. As an absorbing material, the BFTO/MCNTs/P3MT/wax composites were prepared at various loadings of BFTO/MCNTs/P3MT (0.2:0.10:1.0 ~ 0.2:0.30:1.0), and they exhibited strong microwave absorption properties in the range of 1.0-18 GHz. When the loading of BFTO/MCNTs/P3MT is 0.2:0.30:1.0, the composite has a strongest absorbing peak at 11.04 GHz, and achieves a maximum absorbing value of -21.56 dB. The absorbing peak position moves to higher frequencies with the increase of MCNTs content. The mechanism for microwave absorption of these composites has been explained in detail. PMID- 26857940 TI - All-carbon multi-electrode array for real-time in vitro measurements of oxidizable neurotransmitters. AB - We report on the ion beam fabrication of all-carbon multi electrode arrays (MEAs) based on 16 graphitic micro-channels embedded in single-crystal diamond (SCD) substrates. The fabricated SCD-MEAs are systematically employed for the in vitro simultaneous amperometric detection of the secretory activity from populations of chromaffin cells, demonstrating a new sensing approach with respect to standard techniques. The biochemical stability and biocompatibility of the SCD-based device combined with the parallel recording of multi-electrodes array allow: i) a significant time saving in data collection during drug screening and/or pharmacological tests over a large number of cells, ii) the possibility of comparing altered cell functionality among cell populations, and iii) the repeatition of acquisition runs over many cycles with a fully non-toxic and chemically robust bio-sensitive substrate. PMID- 26857941 TI - A randomized, controlled trial of team-based competition to increase learner participation in quality-improvement education. AB - OBJECTIVE: Several barriers challenge resident engagement in learning quality improvement (QI). We investigated whether the incorporation of team-based game mechanics into an evidence-based online learning platform could increase resident participation in a QI curriculum. DESIGN: Randomized, controlled trial. SETTING: Tertiary-care medical center residency training programs. PARTICIPANTS: Resident physicians (n = 422) from nine training programs (anesthesia, emergency medicine, family medicine, internal medicine, ophthalmology, orthopedics, pediatrics, psychiatry and general surgery) randomly allocated to a team competition environment (n = 200) or the control group (n = 222). INTERVENTION: Specialty based team assignment with leaderboards to foster competition, and alias assignment to de-identify individual participants. MAIN OUTCOME MEASURES: Participation in online learning, as measured by percentage of questions attempted (primary outcome) and additional secondary measures of engagement (i.e. response time). Changes in participation measures over time between groups were assessed with a repeated measures ANOVA framework. RESULTS: Residents in the intervention arm demonstrated greater participation than the control group. The percentage of questions attempted at least once was greater in the competition group (79% [SD +/- 32] versus control, 68% [SD +/- 37], P= 0.03). Median response time was faster in the competition group (P= 0.006). Differences in participation continued to increase over the duration of the intervention, as measured by average response time and cumulative percent of questions attempted (each P< 0.001). CONCLUSIONS: Team competition increases resident participation in an online course delivering QI content. Medical educators should consider game mechanics to optimize participation when designing learning experiences. PMID- 26857942 TI - Advances and perspectives in computational prediction of microbial gene essentiality. AB - The minimal subset of genes required for cellular growth, survival and viability of an organism are classified as essential genes. Knowledge of essential genes gives insight into the core structure and functioning of a cell. This might lead to more efficient antimicrobial drug discovery, to elucidation of the correlations between genotype and phenotype, and a better understanding of the minimal requirements for a (synthetic) cell. Traditionally, constructing a catalog of essential genes for a given microbe involved costly and time-consuming laboratory experiments. While experimental methods have produced abundant gene essentiality data for model organisms like Escherichia coli and Bacillus subtilis, the knowledge generated cannot automatically be extrapolated to predict essential genes in all bacteria. In addition, essential genes identified in the laboratory are by definition 'conditionally essential', as they are essential under the specified experimental conditions: these might not resemble conditions in the microorganisms' natural habitat(s). Also, large-scale experimental assaying for essential genes is not always feasible because of the time investment required to setup these assays. The ability to rapidly and precisely identify essential genes in silico is therefore important and has great potential for applications in medicine, biotechnology and basic biological research. Here, we review the advances made in the use of computational methods to predict microbial gene essentiality, perspectives for the future of these techniques and the possible practical applications of essential genes. PMID- 26857944 TI - Three-month-old infants' sensitivity to horizontal information within faces. AB - Horizontal information is crucial to face processing in adults. Yet the ontogeny of this preferential type of processing remains unknown. To clarify this issue, we tested 3-month-old infants' sensitivity to horizontal information within faces. Specifically, infants were exposed to the simultaneous presentation of a face and a car presented in upright or inverted orientation while their looking behavior was recorded. Face and car images were either broadband (UNF) or filtered to only reveal horizontal (H), vertical (V) or this combined information (HV). As expected, infants looked longer at upright faces than at upright cars, but critically, only when horizontal information was preserved in the stimulus (UNF, HV, H). These results first indicate that horizontal information already drives upright face processing at 3 months of age. They also recall the importance, for infants, of some facial features, arranged in a top-heavy configuration, particularly revealed by this band of information. (c) 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 536-542, 2016. PMID- 26857945 TI - A novel hexanuclear titanium(iv)-oxo-iminodiacetate cluster with a Ti6O9 core: single-crystal structure and photocatalytic activities. AB - A new family of hexanuclear titanium(iv)-oxo-carboxylate cluster K7H[Ti6O9(ida)6]Cl2.13H2O {Ti6O9} has been synthesized via the H2O2-assisted reaction between TiCl4 and iminodiacetate ligands. This cluster was fully characterized by single-crystal X-ray diffraction and a wide range of analytical methods, including FT-IR, UV/vis spectroscopy as well as electrochemistry and thermogravimetric analysis. As a new type of carboxylate substituted Ti-oxo cluster, the structural motif of the {Ti6O9} cluster consists of one symmetric {Ti6O6} hexagonal prism with two staggered triangular {Ti3O3} subunits linked by three MU2-O bridges. The {Ti6O9} polyanions are linked by K(+) cations to form a novel 3D architecture. The structural information and stability of the {Ti6O9} polyanion in aqueous solution were thoroughly investigated by solid state/solution NMR, ESI-MS spectroscopy. Moreover, this Ti-oxo cluster exhibits remarkable potential as a visible-light homogeneous photocatalyst for degradation of rhodamine B (RhB). Finally, a proposed peroxotitanium(iv)-mediated photocatalytic pathway involved is illustrated by spectroscopic data. PMID- 26857946 TI - Exploring Parents' Adversities in Pediatric Primary Care. PMID- 26857943 TI - Facing the challenges of multiscale modelling of bacterial and fungal pathogen host interactions. AB - Recent and rapidly evolving progress on high-throughput measurement techniques and computational performance has led to the emergence of new disciplines, such as systems medicine and translational systems biology. At the core of these disciplines lies the desire to produce multiscale models: mathematical models that integrate multiple scales of biological organization, ranging from molecular, cellular and tissue models to organ, whole-organism and population scale models. Using such models, hypotheses can systematically be tested. In this review, we present state-of-the-art multiscale modelling of bacterial and fungal infections, considering both the pathogen and host as well as their interaction. Multiscale modelling of the interactions of bacteria, especially Mycobacterium tuberculosis, with the human host is quite advanced. In contrast, models for fungal infections are still in their infancy, in particular regarding infections with the most important human pathogenic fungi, Candida albicans and Aspergillus fumigatus. We reflect on the current availability of computational approaches for multiscale modelling of host-pathogen interactions and point out current challenges. Finally, we provide an outlook for future requirements of multiscale modelling. PMID- 26857948 TI - Nonpharmacologic Versus Pharmacologic Treatment of Adult Patients With Major Depressive Disorder: A Clinical Practice Guideline From the American College of Physicians. AB - DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the comparative effectiveness of treatment with second-generation antidepressants versus nonpharmacologic treatments for major depressive disorder in adults. METHODS: This guideline is based on a systematic review of published, English-language, randomized, controlled trials from 1990 through September 2015 identified using several databases and through hand searches of references of relevant studies. Interventions evaluated include psychotherapies, complementary and alternative medicines (including acupuncture, omega-3 fatty acids, S-adenosyl-L-methionine, St. John's wort [Hypericum perforatum]), exercise, and second-generation antidepressants. Evaluated outcomes included response, remission, functional capacity, quality of life, reduction of suicidality or hospitalizations, and harms. The target audience for this guideline includes all clinicians, and the target patient population includes adults with major depressive disorder. This guideline grades the evidence and recommendations using ACP's clinical practice guidelines grading system. RECOMMENDATION: ACP recommends that clinicians select between either cognitive behavioral therapy or second-generation antidepressants to treat patients with major depressive disorder after discussing treatment effects, adverse effect profiles, cost, accessibility, and preferences with the patient (Grade: strong recommendation, moderate-quality evidence). PMID- 26857947 TI - Aflibercept for neovascular age-related macular degeneration. AB - BACKGROUND: Central vision loss caused by age-related macular degeneration (AMD) is the leading cause of blindness among the elderly in developed countries. Neovascular AMD is characterized by choroidal neovascularization (CNV). Growth of new blood vessels in patients with neovascular AMD is driven by a complex process that involves a signal protein called vascular endothelial growth factor A (VEGF A). Anti-VEGF drugs that block this protein include ranibizumab, bevacizumab, and aflibercept. OBJECTIVES: To assess and compare the effectiveness and safety of intravitreal injections of aflibercept versus ranibizumab, bevacizumab, or sham for treatment of patients with neovascular AMD. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (Issue 11, 2015), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2015), EMBASE (January 1980 to November 2015), PubMed (1948 to November 2015), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to November 2015), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) (last searched December 4, 2014), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on November 30, 2015. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which aflibercept monotherapy was compared with ranibizumab, bevacizumab, or sham for participants with neovascular AMD who were treatment naive. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures of The Cochrane Collaboration for screening, data abstraction, and study assessment. Two review authors independently screened records, abstracted data, and assessed risk of bias of included studies; we resolved discrepancies by discussion or with the help of a third review author when needed. MAIN RESULTS: We included two RCTs (total of 2457 participants, 2457 eyes). Trial participants had neovascular AMD with active subfoveal choroidal neovascular lesions. Both trials followed the same protocol and compared aflibercept at various doses versus ranibizumab, but they were carried out in different countries. One trial enrolled participants from the United States and Canada, and the second trial was conducted at 172 sites in Europe, Asia Pacific, Latin America, and the Middle East. The overall quality of the evidence was high, and included trials were at low risk for most bias domains assessed; however, both trials were funded by the manufacturers of aflibercept. For the purposes of analysis, we combined aflibercept groups regardless of dosing and analyzed them as a single group.Visual acuity outcomes were similar between aflibercept and ranibizumab groups; at one year, participants in the aflibercept groups showed mean change in best-corrected visual acuity (BCVA) from baseline similar to that of participants in the ranibizumab groups (mean difference (MD) -0.15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, 95% confidence interval (95% CI) -1.47 to 1.17; high-quality evidence). At two years, the mean change in BCVA from baseline was 7.2 ETDRS letters for aflibercept groups versus 7.9 for ranibizumab groups. Sufficient data were not available for calculation of confidence intervals.The proportion of participants who gained 15 or more letters of BCVA by one year of follow-up was approximately 32% for both aflibercept and ranibizumab (RR 0.97, 95% CI 0.85 to 1.11; high-quality evidence), and by two years of follow-up was approximately 31% (RR 0.98, 95% CI 0.85 to 1.12; high-quality evidence). Similar small proportions of participants in the aflibercept and ranibizumab groups lost 15 or more letters of BCVA at one year (RR 0.89, 95% CI 0.61 to 1.30; high quality evidence); this outcome was not reported for two-year follow-up. Data were not reported on the proportion of participants with BCVA worse than 20/200 at one- or two-year follow-up.Participants treated with aflibercept or ranibizumab showed similar improvement in morphological outcomes, as assessed from images (central retinal thickness and CNV size). At one year, the proportion of eyes that achieved dry retina was similar between aflibercept and ranibizumab groups (absence of cystic intraretinal fluid and subretinal fluid on optical coherence tomography (OCT); RR 1.06, 95% CI 0.98 to 1.14; high-quality evidence). In addition, investigators reported no difference in reduction of CNV area between aflibercept- and ranibizumab-treated eyes at one year (MD -0.24 mm(2), 95% CI -0.78 to 0.29; high-quality evidence). Data were not reported for the proportion of eyes with absence of leakage on fluorescein angiography at one- or two-year follow-up.Overall, occurrence of serious systemic adverse events was similar and comparable in aflibercept- and ranibizumab-treated groups at one year (RR 0.99, 95% CI 0.79 to 1.25). Risk of any serious ocular adverse event was lower in the aflibercept group than in the ranibizumab group, but the risk estimate is imprecise (RR 0.62, 95% CI 0.36 to 1.07). As the result of imprecision, we graded the quality of evidence for all adverse events as moderate. AUTHORS' CONCLUSIONS: Results of this review document the comparative effectiveness of aflibercept versus ranibizumab for visual acuity and morphological outcomes in eyes with neovascular AMD. Current available information on adverse effects of each medication suggests that the safety profile of aflibercept is comparable with that of ranibizumab; however, the number of participants who experienced adverse events was small, leading to imprecise estimates of absolute and relative effect sizes. The eight-week dosing regimen of aflibercept represents reduced treatment requirements in comparison with monthly dosing regimens and thus has the potential to reduce treatment burden and risks associated with frequent injections. PMID- 26857949 TI - Effect of Nebulized Albuterol on Serum Lactate and Potassium in Healthy Subjects. AB - OBJECTIVES: The objectives were to determine if nebulized albuterol causes an increase in the serum lactate level compared to placebo and, secondarily, to confirm that albuterol decreases serum potassium levels compared to placebo in patients with normokalemia. METHODS: This was a randomized, double-blind, placebo controlled trial. Twenty-eight healthy adult volunteers were assigned to receive either 10 mg of nebulized albuterol or placebo (nebulized saline) over 1 hour. Serum lactate was measured prior to treatment and at 30 and 70 minutes after the start of treatment. Serum potassium level was measured prior to treatment and at 70 minutes. The primary outcome was the degree of change in lactate level. The secondary outcome was the degree of change in potassium level. RESULTS: In the 14 subjects who received albuterol, the mean increase in lactate was 0.77 mmol/L (95% confidence interval [CI] = 0.52 to 1.02 mmol/L), and the mean decrease in potassium level was 0.5 mEq/L (95% CI = -0.72 to -0.28 mEq/L). Among the subjects who received placebo, the lactate level decreased by 0.15 mmol/L (95% CI = -0.39 to 0.09 mmol/L) and there was no change in potassium level at (0.0 mEq/L [95% CI = -0.21 to 0.21 mEq/L]). These differences are statistically significant (p < 0.0001 and p = 0.003, respectively). CONCLUSION: Nebulized albuterol increases lactate levels and decreases potassium levels in healthy adults. PMID- 26857950 TI - PCDTBT based solar cells: one year of operation under real-world conditions. AB - We present measurements of the outdoor stability of PCDTBT:PC71BM based bulk heterojunction organic solar cells for over the course of a year. We find that the devices undergo a burn-in process lasting 450 hours followed by a TS80 lifetime of up to 6200 hours. We conclude that in the most stable devices, the observed TS80 lifetime is limited by thermally-induced stress between the device layers, as well as materials degradation as a result of edge-ingress of water or moisture through the encapsulation. PMID- 26857951 TI - A comparative study on the in vivo degradation of poly(L-lactide) based composite implants for bone fracture fixation. AB - Composite of nano-hydroxyapatite (n-HAP) surface grafted with poly(L-lactide) (PLLA) (g-HAP) showed improved interface compatibility and mechanical property for bone fracture fixation. In this paper, in vivo degradation of n-HAP/PLLA and g-HAP/PLLA composite implants was investigated. The mechanical properties, molecular weight, thermal properties as well as crystallinity of the implants were measured. The bending strength of the n- and g-HAP/PLLA composites showed a marked reduction from an initial value of 102 and 114 MPa to 33 and 24 MPa at 36 weeks, respectively. While the bending strength of PLLA was maintained at 80 MPa at 36 weeks compared with initial value of 107 MPa. The impact strength increased over time especially for the composites. Significant differences in the molecular weight were seen among all the materials and g-HAP/PLLA appeared the fastest rate of decrease than others. Environmental scanning electron microscope (ESEM) results demonstrated that an apparently porous morphology full of pores and hollows were formed in the composites. The results indicated that the in vivo degradation of PLLA could be accelerated by the g-HAP nanoparticles. It implied that g-HAP/PLLA composites might be a candidate for human non-load bearing bone fracture fixation which needs high initial strength and fast degradation rate. PMID- 26857952 TI - What the ancient Greeks and Romans knew (and did not know) about seasickness. AB - OBJECTIVE: To find and analyze descriptions in ancient Greek and Roman literature that reveal what was known at the time about seasickness. METHODS: A systematic search was made in the original literature beginning in the Greek period with Homer in ca 800 bc and extending up to Aetios Amidenos in the late Roman period in ca 600 ad. RESULTS: Rough seas and unpleasant odors were recognized as the major triggers; susceptibility was greater in persons not adapted to sea travel, of a labile mental state, or with anxiety; nausea, emesis, vertigo, anorexia, faintness, apathy, headache, and impending doom were frequently reported symptoms. Preventive and therapeutic measures included habituation to sea travel, looking at stationary contrasts on the coast, fasting or certain diets, inhaling pleasant fragrances, medicinal plants, and ingesting a mixture of wine and wormwood. CONCLUSION: The triggers, symptoms, and preventive measures of seasickness were well-known in antiquity. The implications for transport of troops and military actions were repeatedly described, e.g., by Livius and Caesar. At that time, the pathophysiologic mechanism was explained by the humoral theory of Empedokles and Aristoteles. Seneca Minor localized the bodily symptoms in various organs such as stomach, gullet, and esophagus, and also attributed them to an imbalance of bile. Recommended medication included ingestion of the plant white hellebore, a violent gastrointestinal poison. This remedy contains various alkaloids but not scopolamine, which today is the most effective anti motion-sickness drug. PMID- 26857953 TI - Visualizing nerve fibers surrounding a brachial plexus tumor using MR diffusion tensor imaging. PMID- 26857954 TI - Animal extremists' threats to neurologic research continue: Neuroreality II. PMID- 26857955 TI - Animal extremists' threats to neurologic research continue: Neuroreality II. PMID- 26857956 TI - Pearls & Oy-sters: Spontaneous intracranial hypotension and posterior reversible encephalopathy syndrome. PMID- 26857957 TI - Teaching NeuroImages: Leukodystrophy and progressive myoclonic epilepsy disclosing DRPLA. PMID- 26857958 TI - Teaching Video NeuroImages: Faciobrachial dystonic seizures: Pathognomonic phenomenology. PMID- 26857959 TI - Neurosteroid Structure-Activity Relationships for Functional Activation of Extrasynaptic deltaGABA(A) Receptors. AB - Synaptic GABAA receptors are primary mediators of rapid inhibition in the brain and play a key role in the pathophysiology of epilepsy and other neurologic disorders. The delta-subunit GABAA receptors are expressed extrasynaptically in the dentate gyrus and contribute to tonic inhibition, promoting network shunting as well as reducing seizure susceptibility. However, the neurosteroid structure function relationship at deltaGABA(A) receptors within the native hippocampus neurons remains unclear. Here we report a structure-activity relationship for neurosteroid modulation of extrasynaptic GABAA receptor-mediated tonic inhibition in the murine dentate gyrus granule cells. We recorded neurosteroid allosteric potentiation of GABA as well as direct activation of tonic currents using a wide array of natural and synthetic neurosteroids. Our results shows that, for all neurosteroids, the C3alpha-OH group remains obligatory for extrasynaptic receptor functional activity, as C3beta-OH epimers were inactive in activating tonic currents. Allopregnanolone and related pregnane analogs exhibited the highest potency and maximal efficacy in promoting tonic currents. Alterations at the C17 or C20 region of the neurosteroid molecule drastically altered the transduction kinetics of tonic current activation. The androstane analogs had the weakest modulatory response among the analogs tested. Neurosteroid potentiation of tonic currents was completely (approximately 95%) diminished in granule cells from delta-knockout mice, suggesting that delta-subunit receptors are essential for neurosteroid activity. The neurosteroid sensitivity of deltaGABA(A) receptors was confirmed at the systems level using a 6-Hz seizure test. A consensus neurosteroid pharmacophore model at extrasynaptic deltaGABA(A) receptors is proposed based on a structure-activity relationship for activation of tonic current and seizure protection. PMID- 26857960 TI - Ethanol Regulation of Synaptic GABAA alpha4 Receptors Is Prevented by Protein Kinase A Activation. AB - Ethanol alters GABAA receptor trafficking and function through activation of protein kinases, and these changes may underlie ethanol dependence and withdrawal. In this study, we used subsynaptic fraction techniques and patch clamp electrophysiology to investigate the biochemical and functional effects of protein kinase A (PKA) and protein kinase C (PKC) activation by ethanol on synaptic GABAA alpha4 receptors, a key target of ethanol-induced changes. Rat cerebral cortical neurons were grown for 18 days in vitro and exposed to ethanol and/or kinase modulators for 4 hours, a paradigm that recapitulates GABAergic changes found after chronic ethanol exposure in vivo. PKA activation by forskolin or rolipram during ethanol exposure prevented increases in P2 fraction alpha4 subunit abundance, whereas inhibiting PKA had no effect. Similarly, in the synaptic fraction, activation of PKA by rolipram in the presence of ethanol prevented the increase in synaptic alpha4 subunit abundance, whereas inhibiting PKA in the presence of ethanol was ineffective. Conversely, PKC inhibition in the presence of ethanol prevented the ethanol-induced increases in synaptic alpha4 subunit abundance. Finally, we found that either activating PKA or inhibiting PKC in the presence of ethanol prevented the ethanol-induced decrease in GABA miniature inhibitory postsynaptic current decay tau1, whereas inhibiting PKA had no effect. We conclude that PKA and PKC have opposing effects in the regulation of synaptic alpha4 receptors, with PKA activation negatively modulating, and PKC activation positively modulating, synaptic alpha4 subunit abundance and function. These results suggest potential targets for restoring normal GABAergic functioning in the treatment of alcohol use disorders. PMID- 26857962 TI - Functionalization-induced changes in the structural and physical properties of amorphous polyaniline: a first-principles and molecular dynamics study. AB - In this paper, we present a first-principles and molecular dynamics study to delineate the functionalization-induced changes in the local structure and the physical properties of amorphous polyaniline. The results of radial distribution function (RDF) demonstrate that introducing -SO3(-)Na(+) groups at phenyl rings leads to the structural changes in both the intrachain and interchain ordering of polyaniline at shorter distances (<=5 A). An unique RDF feature in 1.8-2.1 A regions is usually observed in both the interchain and intrachain RDF profiles of the -SO3(-)Na(+) substituted polymer (i.e. Na-SPANI). Comparative studies of the atom-atom pairs, bond structures, torsion angles and three-dimensional structures show that EB-PANI has much better intrachain ordering than that of Na-SPANI. In addition, investigation of the band gap, density of states (DOS), and absorption spectra indicates that the derivatization at ring do not substantially alter the inherent electronic properties but greatly change the optical properties of polyaniline. Furthermore, the computed diffusion coefficient of water in Na-SPANI is smaller than that of EB-PANI. On the other hand, the Na-SPANI shows a larger density than that of EB-PANI. The computed RDF profiles, band gaps, absorption spectra, and diffusion coefficients are in quantitative agreement with the experimental data. PMID- 26857963 TI - D-sorbitol-induced phase control of TiO2 nanoparticles and its application for dye-sensitized solar cells. AB - Using a simple hydrothermal synthesis, the crystal structure of TiO2 nanoparticles was controlled from rutile to anatase using a sugar alcohol, D sorbitol. Adding small amounts of D-sorbitol to an aqueous TiCl4 solution resulted in changes in the crystal phase, particle size, and surface area by affecting the hydrolysis rate of TiCl4. These changes led to improvements of the solar-to-electrical power conversion efficiency (eta) of dye-sensitized solar cells (DSSC) fabricated using these nanoparticles. A postulated reaction mechanism concerning the role of D-sorbitol in the formation of rutile and anatase was proposed. Fourier-transform infrared spectroscopy, (13)C NMR spectroscopy, and dynamic light scattering analyses were used to better understand the interaction between the Ti precursor and D-sorbitol. The crystal phase and size of the synthesized TiO2 nanocrystallites as well as photovoltaic performance of the DSSC were examined using X-ray diffraction, Raman spectroscopy, field-emission scanning electron microscopy, high-resolution transmission electron microscopy, and photocurrent density-applied voltage spectroscopy measurement techniques. The DSSC fabricated using the anatase TiO2 nanoparticles synthesized in the presence of D-sorbitol, exhibited an enhanced eta (6%, 1.5-fold improvement) compared with the device fabricated using the rutile TiO2 synthesized without D-sorbitol. PMID- 26857964 TI - Neuroprotection by Polynitrogen Manganese Complexes: Regulation of Reactive Oxygen Species-Related Pathways. AB - Cell death in the central nervous system causes neurologic diseases, in which reactive oxygen species (ROS) play a critical role by either inducing cellular oxidative stress or by increasing the cell tolerance against insult. Neurologic diseases may potentially be treated by regulating ROS levels in a certain range with small molecules. We studied preconditioning with two polynitrogen manganese complexes (1 and 2) to regulate intracellular ROS levels in the protection of both the differentiated rat pheochromocytoma cell line (PC12 cells) and neurons against H2O2-induced apoptosis. Pre-treatment with the two complexes attenuated the cell apoptosis caused by H2O2. And the ROS-related neuroprotective mechanisms were explored. Both complexes activate the hypoxia inducible factor-related pathways and increase the cell adaptation to oxidative stress. Pre-treatment with complex 1 eliminated intracellular ROS, which also activated antioxidase system, while short-term incubation of complex 2, generated low levels of ROS leading to cell survival. PMID- 26857965 TI - Cochlear implantation is a therapeutic option for superficial siderosis patients with sensorineural hearing loss. AB - BACKGROUND: Superficial siderosis is a rare disease that results from chronic bleeding in the subarachnoid space. Haemosiderin deposits throughout the subpial layers of the brain and spinal cord lead to progressive sensorineural hearing loss, which is seen in 95 per cent of patients with superficial siderosis. The impact of cochlear implantation on the quality of life of superficial siderosis patients is under debate. CASE REPORT: A 38-year-old male with superficial siderosis presented with bilateral progressive sensorineural hearing loss. The patient underwent cochlear implantation and his quality of life was improved as evaluated by the Abbreviated Profile of Hearing Aid Benefit inventory. CONCLUSION: The remarkable improvement in Abbreviated Profile of Hearing Aid Benefit scores shown in this study indicates that cochlear implantation leads to a better quality of life in superficial siderosis patients. PMID- 26857961 TI - Could Biomarkers Direct Therapy for the Septic Patient? AB - Sepsis is a serious medical condition caused by a severe systemic inflammatory response to a bacterial, fungal, or viral infection that most commonly affects neonates and the elderly. Advances in understanding the pathophysiology of sepsis have resulted in guidelines for care that have helped reduce the risk of dying from sepsis for both children and older adults. Still, over the past three decades, a large number of clinical trials have been undertaken to evaluate pharmacological agents for sepsis. Unfortunately, all of these trials have failed, with the use of some agents even shown to be harmful. One key issue in these trials was the heterogeneity of the patient population that participated. What has emerged is the need to target therapeutic interventions to the specific patient's underlying pathophysiological processes, rather than looking for a universal therapy that would be effective in a "typical" septic patient, who does not exist. This review supports the concept that identification of the right biomarkers that can direct therapy and provide timely feedback on its effectiveness will enable critical care physicians to decrease mortality of patients with sepsis and improve the quality of life of survivors. PMID- 26857966 TI - Differences in body dissatisfaction, weight-management practices and food choices of high-school students in the Bangkok metropolitan region by gender and school type. AB - OBJECTIVE: The present study aimed to compare body dissatisfaction, food choices, physical activity and weight-management practices by gender and school type. DESIGN: A questionnaire was used to obtain height, weight, body image perception using Stunkard's figure rating scale, food choices, physical activity and weight management practices. SETTING: Nine single- and mixed-gender schools located in Bangkok Metropolitan Region, Thailand. SUBJECTS: Students in 10th-12th grade, aged 15-18 years (n 2082). RESULTS: Only 18% of females and 21% of males did not indicate body dissatisfaction. About 66% of females selected a thinner ideal figure than their current figure. Among males, 44% wanted a thinner figure, but 35% wanted a bigger figure. However, univariate analysis found differences by school type but not gender in the degree of body dissatisfaction; students in single-gender schools had more body dissatisfaction. Females reported using more weight-management practices but less physical activity, while males reported healthier food choices. Participants in single-gender schools had healthier food choices compared with those in mixed-gender schools. Adolescents who were at increased risk of a greater degree of body dissatisfaction were females, attended single-gender schools, had lower household income, higher BMI and less physical activity. CONCLUSIONS: Most participants reported being dissatisfied with their current body shape, but the type and level of dissatisfaction and use of weight management practices differed by gender and type of school. These findings suggest that programmes to combat body dissatisfaction should address different risk factors in males and females attending single- and mixed-gender schools. PMID- 26857967 TI - Complex anatomy making it difficult for left atrial appendage closure. AB - Left atrial appendage closure is a useful technique for patients at high thromboembolic risk and contraindications for oral anticoagulation therapy. However, it can be challenging when anatomical difficulties are encountered. We present a unique case of atypical appendage uptake and how we completed the procedure. PMID- 26857968 TI - The Benefits and Pitfalls of the Use of Risk Stratification Tools in Cardiac Surgery. AB - Risk assessment tools are increasingly used in surgery. In cardiac surgery, risk models are used for patient counselling, surgical decision-making, performance benchmarking, clinical research, evaluation of new therapies and quality assurance, among others. However, they have numerous disadvantages which need to be considered. This article evaluates the utility of risk assessment tools in cardiac surgery including a discussion of their advantages and disadvantages. PMID- 26857970 TI - Structure and genetic relationship of five populations from central India based on 15 autosomal STR loci. AB - AIM: To estimate population parameters based on allele frequencies obtained for 15 polymorphic autosomal STR loci investigated in caste and tribal populations of central India (n = 419). METHODS: Multiplexed PCR amplifications of the 15 Autosomal STR Loci were performed and amplified products were genotyped using multi-capillary electrophoresis on an ABI 3100 genetic analyser. Parameters of population genetics and forensic interest based on the allele frequencies were calculated. Genetic affinity of the studied populations among themselves and with previously reported populations of India was also analysed using distance-based NJ tree and using PCA plot. RESULTS: All the 15 STR loci were highly informative and discriminating, with CPD of 0.999 99. Except for Brahmins and Rajput, all other studied populations were in Hardy-Weinberg equilibrium (HWE). The only tribe (Gond) population studied showed significant variation with the other four caste populations (Brahmin, Yadav, Rajput and Muslim) studied and formed a cluster with other previously reported tribal populations of India. Nei's genetic distance based clustering pattern of the NJ tree and the PCA plot showed the same pattern of genetic relationship, i.e. caste and tribal populations formed a distinct cluster. CONCLUSIONS: With respect to the distribution of alleles at each STR locus, the studied loci were found to be substantially polymorphic in all the studied populations, indicating good informativeness of all 15 STR markers. The population data generated in this study are useful for forensic, anthropological and demographic studies. PMID- 26857969 TI - The features of mucosa-associated microbiota in primary sclerosing cholangitis. AB - BACKGROUND: Little is known about the role of the microbiome in primary sclerosing cholangitis. AIM: To explore the mucosa-associated microbiota in primary sclerosing cholangitis (PSC) patients across different locations in the gut, and to compare it with inflammatory bowel disease (IBD)-only patients and healthy controls. METHODS: Biopsies from the terminal ileum, right colon, and left colon were collected from patients and healthy controls undergoing colonoscopy. Microbiota profiling using bacterial 16S rRNA sequencing was performed on all biopsies. RESULTS: Forty-four patients were recruited: 20 with PSC (19 with PSC-IBD and one with PSC-only), 15 with IBD-only and nine healthy controls. The overall microbiome profile was similar throughout different locations in the gut. No differences in the global microbiome profile were found. However, we observed significant PSC-associated enrichment in Barnesiellaceae at the family level, and in Blautia and an unidentified Barnesiellaceae at the genus level. At the operational taxa unit level, most shifts in PSC were observed in Clostridiales and Bacteroidales orders, with approximately 86% of shifts occurring within the former order. CONCLUSIONS: The overall microbiota profile was similar across multiple locations in the gut from the same individual regardless of disease status. In this study, the mucosa associated-microbiota of patients with primary sclerosing cholangitis was characterised by enrichment of Blautia and Barnesiellaceae and by major shifts in operational taxa units within Clostridiales order. PMID- 26857972 TI - Phenotypic flexibility in the energetic strategy of the greater white-toothed shrew, Crocidura russula. AB - The balance between energetic acquisition and expenditure depends on the amount of energy allocated to biological functions such as thermoregulation, growth, reproduction and behavior. Ambient temperature has a profound effect on this balance, with species inhabiting colder climates often needing to invest more energy in thermoregulation to maintain body temperature. This leads to local behavioral and physiological adaptations that increase energetic efficiency. In this study, we investigated the role of activity, behavior and thermogenic capacity in the ability of the greater white-toothed shrew, Crocidura russula, to cope with seasonal changes. Individuals were captured in the Sintra-Cascais Natural Park, a Mediterranean region, and separated into three experimental groups: a control group, acclimated to a 12L:12D photoperiod and temperature of 18-20 degrees C; a winter group, acclimatized to natural winter fluctuations of light and temperature; and a summer group, acclimatized to natural summer fluctuations of light and temperature. No differences were found in resting metabolic rate and nonshivering thermogenesis between the three groups. However, winter shrews significantly reduced their activity, particularly at night, compared to the control and summer groups. Differences in torpor use were also found between groups, with winter shrews entering torpor more frequently and during shorter periods of time than summer and control shrews. Our results indicate C. russula from Sintra relies on the flexibility of energy saving mechanisms, namely daily activity level and torpor use, to cope with seasonal changes in a Mediterranean climate, rather than mechanisms involving body heat production. PMID- 26857971 TI - Distance makes the difference in thermography for ecological studies. AB - Surface temperature drives many ecological processes and infrared thermography is widely used by ecologists to measure the thermal heterogeneity of different species' habitats. However, the potential bias in temperature readings caused by distance between the surface to be measured and the camera is still poorly acknowledged. We examined the effect of distance from 0.3 to 80m on a variety of thermal metrics (mean temperature, standard deviation, patch richness and aggregation) under various weather conditions and for different structural complexity of the studied surface types (various surfaces with vegetation). We found that distance is a key modifier of the temperature measured by a thermal infrared camera. A non-linear relationship between distance and mean temperature, standard deviation and patch richness led to a rapid under-estimation of the thermal metrics within the first 20m and then only a slight decrease between 20 and 80m from the object. Solar radiation also enhanced the bias with increasing distance. Therefore, surface temperatures were under-estimated as distance increased and thermal mosaics were homogenized at long distances with a much stronger bias in the warmer than the colder parts of the distributions. The under estimation of thermal metrics due to distance was explained by atmospheric composition and the pixel size effect. The structural complexity of the surface had little effect on the surface temperature bias. Finally, we provide general guidelines for ecologists to minimize inaccuracies caused by distance from the studied surface in thermography. PMID- 26857973 TI - Early evolution of the thermometer and application to clinical medicine. AB - By the time of Hippocrates and Galen the notion of fevers and temperature were known. Through ensuing centuries, ancient Greek, Roman, and medieval savants and physicians made additional contributions to the understanding of fever, temperature, and thermometry. By the end of that era, there was a working definition of what constitutes a rationale temperature scale, the distinction between fever as a symptom and fever as a disease, an elaborate classification scheme for temperature, hypotheses as to the causes of fever, and methods for measuring fevers. Based on the definition of fever at that time, the 16th century scientist Galileo promulgated production of thermometric instruments hundreds of years before they were routinely used in the clinical setting. In this work we examine the history of fever and clinical thermometry in the ancient world through the end of the eighteenth century with descriptions of instruments for its measure and human relationship to fever. PMID- 26857975 TI - The influence of thermal biology on road mortality risk in snakes. AB - Road mortality is a significant threat to terrestrial vertebrates in many areas, and the novel thermal environment of black-topped roads may represent ecological traps for some species and demographic groups. We investigated the relationship between ambient temperature and on-road detection in a snake assemblage in southeastern Louisiana by comparing observations of live snakes on a black-topped road, across measurements of air temperature and road temperature on survey days. Analyses indicated on-road detection of snakes was significantly influenced by ambient temperature conditions for five snake species. Additionally, road temperatures, and the difference between air and road temperatures, were strong drivers of on-road snake detections. Permutation analysis methods revealed that significant temperature related group (species or sex) structure exists in occurrences of snakes on the roadway, and that road temperature was the strongest driver of species differences. We also compared how air and road temperatures affected occurrence on the road between sexes in the colubrid snakes Nerodia fasciata, Nerodia cyclopion, Thamnophis proximus, and Pantherophis obsoletus. Males and females of the viviparous species N. fasciata, N. cyclopion, and T. proximus diverged significantly in temperature preferences, with females found under warmer conditions, while males and females of the oviparous species P. obsoletus did not. Road temperature was also the strongest driver of differences between sexes. Our results indicate that black-topped roads are an ecological trap that is heavily influenced by sex, reproductive condition, and species specific thermoregulatory requirements, particularly for viviparous species. PMID- 26857974 TI - Simulation of scalp cooling by external devices for prevention of chemotherapy induced alopecia. AB - Hypothermia of the scalp tissue during chemotherapy treatment (scalp cooling) has been shown to reduce or prevent chemotherapy-induced hair loss. In this study, numerical models are developed to investigate the interaction between different types of external scalp cooling devices and the human scalp tissue. This work focuses on improving methods of modeling scalp cooling devices as it relates specifically to the prevention of chemotherapy-induced alopecia. First, the cooling power needed for any type of device to achieve therapeutic levels of scalp hypothermia is investigated. Subsequently, two types of scalp cooling devices are simulated: a pre-cooled/frozen cap design and a liquid-cooled cap design. For an average patient, simulations show that 38.5W of heat must be extracted from the scalp tissue for this therapy in order to cool the hair follicle to 22 degrees C. In practice, the cooling power must be greater than this amount to account for thermal losses of the device. Simulations show that pre-cooled and liquid-cooled cap designs result in different tissue temperatures over the course of the procedure. However, it is the temperature of the coolant that largely determines the resulting tissue temperature. Simulations confirm that the thermal resistance of the hair/air layer has a large impact on the resulting tissue temperatures. The results should be correlated with experimental data as an effort to determine the optimal parameter choices for this model. PMID- 26857976 TI - Teratological deformities of pedipalps in the Tegenaria atrica spider, induced by low and high temperatures applied alternately. AB - The study was aimed at demonstrating the relationship between temperature (as a factor which disturbs morphogenesis) and deformities in the front part of the prosoma in Tegenaria atrica. By exposing spider embryos to alternating temperatures of 14 and 32 degrees C for the first 10 days of embryonic development, i.e. until the first metameres of the prosoma appeared on the germ band, we obtained individuals with a range of anomalies including those which affected the prosomal morphology. We selected five spiders with deformities of pedipalps or of pedipalps and walking legs for comprehensive analysis. The results indicate a relationship between temperature applied as a teratogenic factor and anomalies in the front part of the prosoma. PMID- 26857977 TI - The relationship between body mass index and scrotal temperature among male partners of subfertile couples. AB - This study aimed to determine the relationship between scrotal temperature (ST) and body mass index (BMI). Data were collected from 471 male partners in subfertile couples who visited a Korean medical infertility center between March 2013 and November 2014. Participants were classified into three groups according to their BMI (<25.0, 25.0-29.9, and >30kg/m(2)). Scrotal temperature index (STI)( degrees C) was defined as the mean left and right skin temperature difference (DeltaT) between the thigh and testicle. Mean STI and standard deviation (mean+/ SD) of the underweight and normal, overweight, and obese groups were -1.50+/ 0.95, -1.08+/-0.83, and -0.57+/-0.93 degrees C, respectively. The obese and overweight groups had higher STI than the underweight and normal groups (p<0.001). Increased BMI is associated with higher ST. To examine this causal relationship, further assessment of the role of weight loss or gain on scrotal temperature is warranted. PMID- 26857978 TI - The effects of single versus twice daily short term heat acclimation on heat strain and 3000m running performance in hot, humid conditions. AB - Endurance performances are impaired under conditions of elevated heat stress. Short term heat acclimation (STHA) over 4-6 days can evoke rapid adaptation, which mitigate decrements in performance and alleviate heat strain. This study investigated the efficacy of twice daily heat acclimation (TDHA) compared to single session per day heat acclimation (SDHA) and normothermic training, at inducing heat acclimation phenotype and its impact upon running performance in hot, humid conditions. Twenty one, moderately trained males were matched and assigned to three groups; SDHA (mean+/-SD) (peak oxygen consumption [VO2peak] 45.8+/-6.1mLkg(-1)min(-1), body mass 81.3+/-16.0kg, stature 182+/-3cm), TDHA (46.1+/-7.0mLkg(-1)min(-1), 80.1+/-11.9kg, 178+/-4cm) or control (CON) (47.1+/ 3.5mLkg(-1)min(-1), 78.6+/-16.7kg, 178+/-4cm). Interventions consisted of 45min cycling at 50% VO2peak, once daily for 4d (SDHA) and twice daily for 2d (TDHA), in 35 degrees C, 60% relative humidity (RH), and once daily for 4 days (CON) in 21 degrees C, 40% RH. Participants completed a pre- and post-intervention 5km treadmill run trial in 30 degrees C, 60% RH, where the first 2km were fixed at 40% VO2peak and the final 3km was self-paced. No statistically significant interaction effects occurred within- or between-groups over the 2-4 days intervention. While within-group differences were found in physiological and perceptual measures during the fixed intensity trial post-intervention, they did not statistically differ between-groups. Similarly, TDHA (-36+/-34s [+3.5%]) and SDHA (-26+/-28s [+2.8%]) groups improved 3km performances (p=0.35), but did not differ from CON (-6+/-44s [+0.6%]). This is the first study to investigate the effects of HA twice daily and compare it with traditional single session per day STHA. These STHA protocols may have the ability to induce partial adaptive responses to heat stress and possibly enhance performance in environmentally challenging conditions, however, future development is warranted to optimise the administration to provide a potent stimuli for heat adaptation in athletic and military personnel within a rapid regime. PMID- 26857979 TI - Effect of in vitro zinc supplementation on HSPs expression and Interleukin 10 production in heat treated peripheral blood mononuclear cells of transition Sahiwal and Karan Fries cows. AB - The changing climatic scenario with apprehended rise in global temperature is likely to affect the livestock adversely vis-a-vis production and reproduction. This has prompted more focus in addressing the unfavorable effects of thermal stress in livestock system. Presuming that the trace element zinc is indispensible for cellular antioxidant system and immune function, the present study was designed to investigate the effect of zinc treatment on heat stress alleviation and immune modulation in peripheral blood mononuclear cells (PBMC) of indigenous and crossbred transition cows. Twelve cows, six each of Sahiwal and Karan Fries (KF) in their second parity with confirmed pregnancy were selected for the experiment. The blood samples were collected at -21, 0 and +21 days in relation to expected date of calving. The experiment was carried out in vitro after isolating PBMC from whole blood. The 48h cultured PBMC were subjected to assorted levels of exposures viz. 37 degrees C, 42 degrees C to impose heat stress and 42 degrees C+zinc to alleviate heat stress and modulate immunity. The PBMC viability was 86%, 69% and 78%, respectively. The mRNA expression of heat shock proteins (HSP 40, 70 and 90alpha) and Interleukin-10 (IL-10) production varied between the two breeds vis-a-vis days and levels of exposure. The mRNA expression of HSP40 and HSP70 was significantly (P<0.05) higher in Karan Fries than the Sahiwal cows. Both the breeds showed maximum expression of HSP on the day of parturition, more so in KF than Sahiwal. There was a significant (P<0.05) difference in the HSP mRNA expression at different levels of exposure. Zinc treatment to heat stressed PBMC caused a significant (P<0.05) down regulation of HSP. For immune status, anti-inflammatory cytokine, IL-10 in the culture supernatant was accessed. The IL-10 was significantly (P<0.05) higher in Karan Fries (168.18+/-14.09pg/ml) than the Sahiwal cows (147.24+/-11.82pg/ml). The IL 10 concentration was highest on the day of calving. Zinc treatment reduced the IL 10 concentration. From the study, it could be concluded that the zinc supplementation in heat stressed PBMC can ameliorate thermal stress and modulate immune response which can act as a model for reducing heat stress during the periparturient period in tropical livestock. PMID- 26857980 TI - The peak of thermoregulation effectiveness: Thermal biology of the Pyrenean rock lizard, Iberolacerta bonnali (Squamata, Lacertidae). AB - We studied, at 2200m altitude, the thermal biology of the Pyrenean rock lizard, Iberolacerta bonnali, in the glacial cirque of Cotatuero (National Park of Ordesa, Huesca, Spain). The preferred thermal range (PTR) of I. bonnali indicates that it is a cold-adapted ectotherm with a narrow PTR (29.20-32.77 degrees C). However, its PTR (3.57 degrees C) is twice as wide as other Iberolacerta lizards, which may be explained by its broader historical distribution. The studied area is formed by a mosaic of microhabitats which offer different operative temperatures, so that lizards have, throughout their entire daily period of activity, the opportunity to choose the most thermally suitable substrates. I. bonnali achieves an effectiveness of thermoregulation of 0.95, which makes it the highest value found to date among the Lacertidae, and one of the highest among lizards. Their relatively wide distribution, their wider PTR, and their excellent ability of thermoregulation, would make I. bonnali lizards less vulnerable to climate change than other species of Iberolacerta. Thanks to its difficult access, the studied area is not visited by a large number of tourists, as are other areas of the National Park. Thus, it is a key area for the conservation of the Pyrenean rock lizard. By shuttling between suitable microhabitats, lizards achieve suitable body temperatures during all day. However, such thermally suitable microhabitats should vary in other traits than thermal quality, such as prey availability or predation risk. Hence, it seems that these not-thermal traits are not constraining habitat selection and thermoregulation in this population. Therefore, future research in this population may study the causes that would lead lizards to prioritize thermoregulation to such extent in this population. PMID- 26857981 TI - Thermal development of Cephalonomia tarsalis (Hymenoptera: Bethylidae) parasitoid of the saw-toothed stored product beetles of the genus Oryzaephilus sp. (Coleoptera: Sylvanidae). AB - The effect of temperature on the development and survival of Cephalonomia tarsalis (Ashmead) (Hymenoptera: Bethylidae), larval ectoparasitoid of beetles of Oryzaephilus sp. (Coleoptera: Silvanidae) was studied in the laboratory. Durations of the development of the egg, larva and pupa were measured in eight constant temperatures (15, 17.5, 20, 25, 30, 32.5, 35 and 37.5 degrees C) parasitizing larvae of the saw-toothed beetle Oryzaephilus surinamensis (L.) (Coleoptera: Silvanidae). The duration of development was decreased with temperature increase within the range 17.5-32.5 degrees C. Survival was higher when immatures were exposed to medium temperatures (20-30 degrees C) compared with those lived in a more extreme temperature regime (<20 and >30 degrees C). Wasps failed to complete their development at 15 and 37.5 degrees C. Thermal parameters (upper, lower and optimum developmental threshold, thermal constant) were estimated by fitting the linear and a non-linear (Logan I) model to our data. Upper and lower developmental thresholds ranged between 35.1-37.0 degrees C and 13.2-13.8 degrees C, respectively. The optimum temperature for development was estimated between 33.6 degrees C and 34.6 degrees C. Tests for developmental rate isomorphy (DRI) showed that change in the average proportion of time spent in each developmental stage was marginally significant, proving that development of C. tarsalis is probably incompatible with DRI. However, this conclusion is questionable given that lower developmental thresholds did not differ significantly among various developmental stages (bootstrap test). Thermal constant for total development was calculated 212.4 degree-days. Our results are discussed not only on the basis of thermal biology, but also of improving the efficiency of C. tarsalis as biocontrol agent. PMID- 26857982 TI - Modeling conductive cooling for thermally stressed dairy cows. AB - Conductive cooling, which is based on direct contact between a cow lying down and a cooled surface (water mattress, or any other heat exchanger embedded under the bedding), allows heat transfer from the cow to the cooled surface, and thus alleviate heat stress of the cow. Conductive cooling is a novel technology that has the potential to reduce the consumption of energy and water in cooling dairy cows compared to some current practices. A three-dimensional conduction model that simulates cooling thermally-stressed dairy cows was developed. The model used a computational fluid dynamics (CFD) method to characterize the air-flow field surrounding the animal model. The flow field was obtained by solving the continuity and the momentum equations. The heat exchange between the animal and the cooled water mattress as well as between the animal and ambient air was determined by solving the energy equation. The relative humidity was characterized using the species transport equation. The conduction 3-D model was validated against experimental temperature data and the agreement was very good (average error is 4.4% and the range is 1.9-8.3%) for a mesh size of 1117202. Sensitivity analyses were conducted between heat losses (sensible and latent) with respect to air temperature, relative humidity, air velocity, and level of wetness of skin surface to determine which of the parameters affect heat flux more than others. Heat flux was more sensitive to air temperature and level of wetness of the skin surface and less sensitive to relative humidity. PMID- 26857983 TI - Cool Bands: Wing bands decrease rate of heating, but not equilibrium temperature in Anartia fatima. AB - Butterflies regulate their internal thoracic temperature in order to optimize performance activities (e.g. flight, foraging). Previous research has shown that butterfly wings, particularly the innermost portions, play a role in thermoregulation. We investigated to see whether a lightly colored wing band would alter the thermal properties of the banded peacock butterfly (Anartia fatima) with two within subject experiments in a laboratory setting: (1) band color manipulation in which euthanized individuals were heated to thermal equilibrium with the band unaltered and then again with the wing darkened; (2) wing ablation in which individuals already run through experiment 1 were heated to equilibrium two more times; once with the outer portion of the wing including the band removed and then with the entire wing removed. Individuals were spread so that the dorsal surface of the wing was exposed to illumination from a lamp suspended above. Twelve Anartia fatima males were collected in Panama and were run through experiment one. Four individuals were run through experiment two. We found no effect of darkening the band on the internal thoracic equilibrium temperature, but the darkened band did increase the rate of heating. The wing ablation experiment revealed that wing removal lowered the internal thoracic equilibrium temperature but did not affect the heating rate. Therefore we show that butterfly bands may be important in butterfly thermoregulation and we discuss the importance of the wing band on thermoregulatory abilities in Anartia fatima with respect to the butterfly's natural history. We conclude that the wing band may allow butterflies to reduce heat stress induced by their warm environments. PMID- 26857984 TI - Optimal foraging behavior and the thermal neutral zone of Peromyscus leucopus during winter: A test using natural and controlled ambient temperatures. AB - Endotherms foraging at temperatures outside of their thermal neutral zone (TNZ) pay an increased energetic cost. We asked if thermally-induced changes in foraging costs influence quitting harvest rate (QHR) of mice. We predicted that mice foraging during the winter would have a higher QHR in more costly colder conditions. We conducted our study with wild caught Peromyscus leucopus in an enclosure located in West Terre Haute, Indiana. We assayed changes in QHR using the forager's giving up density (GUD), which is the amount of uneaten seeds reaming in a tray after foraging activity. Each night from January 12th to March 13th, we assigned 4 trays as "cold trays" (at ambient temperature), and 4 trays as "hot trays" (trays with a ceramic heat element that increased the temperatures of feeding trays ca. 10-15 degrees C). GUDs (and therfore QHRs) increased as a function of decreasing ambient temperature. Furthermore there was an interaction between tray temperature and ambient temperature; namely, on cool nights mice had lower GUDs in the "hot trays", but on warm nights mice had lower GUDs in the "cold trays". The TNZ for P. leucopus actively foraging during winter may be closer to the environmental average temperature than typically measured in the laboratory. Overall, these results support the idea that QHR is related to an animal's foraging in thermally challenged conditions. We present a unique way of measuring an animal's TNZ in the field using behavioral indicators. PMID- 26857985 TI - A protocol for analysing thermal stress in insects using infrared thermography. AB - The study of insect responses to thermal stress has involved a variety of protocols and methodologies that hamper the ability to compare results between studies. For that reason, the development of a protocol to standardize thermal assays is necessary. In this sense, infrared thermography solves some of the problems allowing us to take continuous temperature measurements without handling the individuals, an important fact in cold-blooded organisms like insects. Here, we present a working protocol based on infrared thermography to estimate both cold and heat thermal stress in insects. We analyse both the change in the body temperature of individuals and their behavioural response. In addition, we used partial least squares regression for the statistical analysis of our data, a technique that solves the problem of having a large number of variables and few individuals, allowing us to work with rare or endemic species. To test our protocol, we chose two species of congeneric, narrowly distributed dung beetles that are endemic to the southeastern part of the Iberian Peninsula. With our protocol we have obtained five variables in the response to cold and twelve in the response to heat. With this methodology we discriminate between the two flightless species of Jekelius through their thermal response. In response to cold, Jekelius hernandezi showed a higher rate of cooling and reached higher temperatures of stupor and haemolymph freezing than Jekelius punctatolineatus. Both species displayed similar thermoregulation ranges before reaching lethal body temperature with heat stress. Overall, we have demonstrated that infrared thermography is a suitable method to assess insect thermal responses with a high degree of sensitivity, allowing for the discrimination between closely related species. PMID- 26857986 TI - Review article: Mucosa-associated lymphoid tissue (MALT)-type lymphoma of ocular adnexa. Biology and treatment. AB - Over the last decades, we have witnessed an increase in the incidence of primary ocular adnexa lymphomas (POALs) probably because advances in imaging techniques have enabled precise biopsies of the tumors. The ocular tissue biopsy, before the initiation of the appropriate treatment, is mandatory and necessary for a correct diagnosis of POALs by the use of immunophenotyping and a correct molecular classification. Only in a minority of cases the ocular adnexa are secondarily affected by a systemic disease. Among the POALs, the most common is the primary extra nodal lymphoma of MALT-type (POAML). POAML is rarely symptomatic in the early phase of the disease. As a consequence, often we see a delay in ophthalmic consultations and diagnosis. The clinical manifestations are heterogeneous and its management requires a multidisciplinary approach involving ophthalmologists, hematologists and radiotherapists. PMID- 26857987 TI - Cytotoxic chemotherapy: Still the mainstay of clinical practice for all subtypes metastatic breast cancer. AB - Cytotoxic chemotherapy remains central to the treatment of all subtypes of metastatic breast cancer (MBC). We review evidence-based chemotherapy options for women with MBC after an anthracycline and a taxane including re-challenge with anthracycline or taxane, capecitabine, eribulin and ixabepilone as a single agent or combination with capecitabine (not approved in the EU); and the vinca alkaloid vinflunine as single agent or combined with either capecitabine/gemcitabine (also not approved EU or USA). Etirinotecan pegol, comprising irinotecan bound to polyethylene glycol by a biodegradable linker, is a new cytotoxic agent for patients with MBC that has achieved encouraging response rates in phase II studies; it has been further evaluated in the phase III BEACON trial. New cytotoxics should address novel targets or modes of delivery, achieve meaningful improvements in outcomes and seek to identify predictive biomarker(s). PMID- 26857988 TI - Bioaccumulation characteristics of polybrominated diphenyl ethers in the marine food web of Bohai Bay. AB - In recent years, polybrominated diphenyl ethers (PBDEs) are ubiquitous environmental contaminants, but its bioaccumulation and debromination in biota have remained largely unclear. In this study, we analyzed six PBDEs (BDE47, 99, 100, 153, 154, and 209) in various tissues (i.e., viscera, muscle, and gill) of 11 types of marine organisms including zooplankton, invertebrate and fish. The concentrations of six PBDE including BDE209 in marine organisms ranged from 0.75 to 7.29 ng/g dry weight, BDE209 from 0.46 to 6.78 ng/g dry weight, respectively. BDE209 was the dominant congener in all samples, followed by BDE47. The concentration ratio of BDE47, 99, 154 to SigmaPBDEs in various tissues of organisms (i.e., Rapana venosa, shrimp, crab, cuttlefish, octopus, Synechogobius hasta, tonguefish and wolfish) increased, while the concentration ratio of BDE209 to SigmaPBDEs decreased. Large differences of the concentration ratios between BDE99 and BDE100 in tissues of crab was found, ranging from 32:68 in crab viscera to 83:17 in crab leg muscle. Biomagnification factors for individual PBDE congeners ranged from 0.16 to 78.6. In general, the BMFs for BDE209 in muscle were higher than those in viscera within feeding relationships. The study results suggesting BDE209 can be biodegraded to BDE47 through BDE154 and BDE99 in marine organism, its metabolite importantly influenced by organism type not trophic level; higher percentage of BDE154 was found in viscera than that in other tissues in the analyzed marine organisms of Bohai Bay. PMID- 26857989 TI - In vivo passive mechanical properties estimation of Achilles tendon using ultrasound. AB - A methodology is proposed for estimating Achilles tendon tangent modulus in vivo, to account for its large deformations and non-linear behavior. True stress is found dividing the axial force by the tendon true cross-sectional area (CSA), whose shrinking caused by axial tension is estimated with Poisson's coefficient. The true strain is calculated as the integral of incremental deformations along the tendon length change. Triceps surae tendon CSA and ankle moment arm, with the foot at relaxed equilibrium position, are estimated from subject-personalized data. Healthy males (N=19) volunteered for the study. The test consisted of passive ankle mobilization at the dynamometer with 5 degrees /s velocity, from 30 degrees of plantar flexion to the limit of dorsiflexion. Ultrasound was used to track myotendinous junction (MTJ) and tendon elongation, with the probe oriented over the medial gastrocnemius. Non-linear tendon stiffness pattern was observed during the joint range of motion, reaching 200N/mm peaks for the subjects with greater amplitudes of maximum dorsiflexion. The maximum values of modulus of elasticity, calculated from usual engineering stress and strain, (188.56+/ 99.19MPa) were smaller than those reported in the literature for active maximum voluntary contractions tests. Maximum values for tangent modulus from true stress and strain were 312.38+/-171.95MPa. Such differences are likely to increase in large deformations. PMID- 26857990 TI - A probabilistic orthopaedic population model to predict fatigue-related subacromial geometric variability. AB - Fatigue-related glenohumeral and scapulothoracic kinematic relationships, in addition to morphological characteristics of the scapula and humerus, affect the dimensions of the subacromial space. Each exhibits considerable interpersonal variability, which if only considering the mean, can lead to misleading population estimations of subacromial impingement risk, particularly for outliers. Additionally, the relative influence of each parameter on subacromial space variability is unclear. Applying empirically-derived morphological and kinematic distributions (n=31), this research used Advanced Mean Value and Monte Carlo probabilistic modeling approaches to predict the distribution of the minimum subacromial space width (SAS) and establish which parameters contributed more to modulating the SAS. The predicted SAS differed by 8mm between 1% and 99% confidence intervals. While the SAS was not influenced by muscle fatigue, the space reduced with arm elevation to magnitudes between 4.5 and 5mm. This reduction resulted in an estimated 65-75% of the population at risk for tissue compression at elevation angles>=90 degrees when considering the interposed tissue thickness. Morphological parameters, notably glenoid inclination, showed higher relative importance for modulating the predicted SAS across conditions, while kinematic parameters (humeral head translation, scapular orientation), which differed by elevation angle and fatigue state, demonstrated less consistent importance levels across experimental conditions. Overall, the findings reinforce the shoulder health risks related to overhead activities, as they pose an increased likelihood of mechanical rotator cuff tendon compression. Further, probabilistic methods are highly innovative, in that they are capable of determining relative parameter importance and subsequently identifying key injury risk factors. As glenoid inclination is difficult to diagnose and treat, and is associated with superior humeral head translation, interventions to improve rotator cuff strength and glenohumeral stability are recommended, particularly in populations exposed to overhead postures. PMID- 26857991 TI - Shoulder arthroplasty in Germany: 2005-2012. AB - INTRODUCTION: The field of shoulder endoprothetics has undergone a rapid development in the last years. The purpose of the study was to provide an overview of the development of shoulder arthroplasties in Germany from 2005 until 2012. This study hypothesized that the surgical procedures of the shoulder joint is still increasing and have not reached a plateau until 2012. METHODS: Data of the German federal statistical office from 2005 until 2012 were analyzed to quantify hemiarthroplasty, anatomic total shoulder and reversed total shoulder arthroplasty rates depending on age, gender and main coded indications. Procedure codes and diagnosis were analyzed for each year. Comparative analyses were used to visualize the difference between the types of shoulder endoprostheses. RESULTS: A total number of 139.272 shoulder arthroplasties were performed between 2005 and 2012. Total should arthroplasties have increased continuously until 2009. In 2009 more total shoulder arthroplasties have been performed than hemiprothesis implantations, which have culminated in 2008. All in all, women have been treated 3-fold higher than men regarding hemiarthroplasty, total shoulder arthroplasties or reversed total shoulder arthroplasties. Under the age of 60 years the majority of treated patients were male. CONCLUSION: Since 2005 shoulder arthroplasties are still increasing in Germany, whereas a slight reduction could be detected for shoulder hemiarthroplasty from 2009 up until 2012. Meanwhile total shoulder arthroplasties and reversed total shoulder arthroplasties are still increasing. Women have experienced a 3-fold higher hemiarthroplasty, total shoulder and reversed shoulder arthroplasties than men except for individual younger than 60 years. PMID- 26857993 TI - Optimization of the Liquid Culture Medium Composition to Obtain the Mycelium of Agaricus bisporus Rich in Essential Minerals. AB - Agaricus bisporus species (J.E. Lange) Imbach one of the most popular Basidiomycota species was chosen for the research because of its dietary and medicinal value. The presented herein studies included determination of essential mineral accumulation level in the mycelium of A. bisporus, cultivated on liquid cultures in the medium supplemented with addition of the chosen metals' salts. Quantitative analyses of Zn, Cu, Mg, and Fe in liquid cultures made it possible to determine the relationship between accumulation of the selected mineral in A. bisporus mycelium and the culture conditions. Monitoring of the liquid cultures and determination of the elements' concentrations in mycelium of A. bisporus were performed using the flame technique of AAS method. Concentration of Zn in the mycelium, maintained in the medium with the addition of its salt, was in a very wide range from 95.9 to 4462.0 mg/g DW. In the analyzed A. bisporus mycelium, cultured in the medium enriched with copper salt, this metal concentration changed from 89.79 to 7491.50 mg/g DW; considering Mg in liquid cultured mycelium (medium with Mg addition), its concentration has changed from 0.32 to 10.55 mg/g DW. The medium enriched with iron salts has led to bioaccumulation of Fe in mycelia of A. bisporus. Determined Fe concentration was in the range from 0.62 to 161.28 mg/g DW. The proposed method of liquid A. bisporus culturing on medium enriched with the selected macro- and microelements in proper concentrations ratio have led to obtaining maximal growth of biomass, characterized by high efficiency of the mineral accumulation. As a result, a dietary component of increased nutritive value was obtained. PMID- 26857996 TI - Access to medicines for CVD-what's the trade-off? PMID- 26857997 TI - Community health workers for recovery from acute coronary syndrome. PMID- 26857995 TI - AAV8-mediated expression of N-acetylglucosamine-1-phosphate transferase attenuates bone loss in a mouse model of mucolipidosis II. AB - Mucolipidoses II and III (ML II and ML III) are lysosomal disorders in which the mannose 6-phosphate recognition marker is absent from lysosomal hydrolases and other glycoproteins due to mutations in GNPTAB, which encodes two of three subunits of the heterohexameric enzyme, N-acetylglucosamine-1-phosphotransferase. Both disorders are caused by the same gene, but ML II represents the more severe phenotype. Bone manifestations of ML II include hip dysplasia, scoliosis, rickets and osteogenesis imperfecta. In this study, we sought to determine whether a recombinant adeno-associated viral vector (AAV2/8-GNPTAB) could confer high and prolonged gene expression of GNPTAB and thereby influence the pathology in the cartilage and bone tissue of a GNPTAB knock out (KO) mouse model. The results demonstrated significant increases in bone mineral density and content in AAV2/8 GNPTAB-treated as compared to non-treated KO mice. We also showed that IL-6 (interleukin-6) expression in articular cartilage was reduced in AAV2/8-GNPTAB treated ML II mice. Together, these data suggest that AAV-mediated expression of GNPTAB in ML II mice can attenuate bone loss via inhibition of IL-6 production. This study emphasizes the value of the MLII KO mouse to recapitulate the clinical manifestations of the disease and highlights its amenability to therapy. PMID- 26857994 TI - Loss of the transcription factor Meis1 prevents sympathetic neurons target-field innervation and increases susceptibility to sudden cardiac death. AB - Although cardio-vascular incidents and sudden cardiac death (SCD) are among the leading causes of premature death in the general population, the origins remain unidentified in many cases. Genome-wide association studies have identified Meis1 as a risk factor for SCD. We report that Meis1 inactivation in the mouse neural crest leads to an altered sympatho-vagal regulation of cardiac rhythmicity in adults characterized by a chronotropic incompetence and cardiac conduction defects, thus increasing the susceptibility to SCD. We demonstrated that Meis1 is a major regulator of sympathetic target-field innervation and that Meis1 deficient sympathetic neurons die by apoptosis from early embryonic stages to perinatal stages. In addition, we showed that Meis1 regulates the transcription of key molecules necessary for the endosomal machinery. Accordingly, the traffic of Rab5(+) endosomes is severely altered in Meis1-inactivated sympathetic neurons. These results suggest that Meis1 interacts with various trophic factors signaling pathways during postmitotic neurons differentiation. PMID- 26857998 TI - Constraints and challenges in access to insulin: a global perspective. AB - Substantial attention has been given to the issue of access to medicines for communicable diseases; however, access to essential medicines for diabetes, especially insulin, has had insufficient focus. Although insulin was discovered in 1921, the drug is unattainable to many globally, and this Review aims to highlight the range and complexity of factors that contribute to this unattainability. Manufacturers' selling prices of various insulin formulations and presentations, duties, taxes, mark-ups, and other supply chain costs affect the price of insulin and hence the drug's affordability to health systems and individuals. Unlike drugs for HIV and AIDS, the production of generic or biosimilar insulin has not had an effect on the overall market. Other factors contributing to poor availability of insulin include its quantification at the national level, in-country distribution, and determination of needs at lower levels of the health system. Although insulin is essential for the survival of people with type 1 diabetes and is needed for improved management of diabetes for some people with type 2 diabetes, very little has been done globally to address the issue of access, despite the UN's political commitment to address non communicable diseases and ensure universal access to drugs for these disorders. PMID- 26858000 TI - Campylobacter QMRA: A Bayesian Estimation of Prevalence and Concentration in Retail Foods Under Clustering and Heavy Censoring. AB - A Bayesian statistical temporal-prevalence-concentration model (TPCM) was built to assess the prevalence and concentration of pathogenic campylobacter species in batches of fresh chicken and turkey meat at retail. The data set was collected from Finnish grocery stores in all the seasons of the year. Observations at low concentration levels are often censored due to the limit of determination of the microbiological methods. This model utilized the potential of Bayesian methods to borrow strength from related samples in order to perform under heavy censoring. In this extreme case the majority of the observed batch-specific concentrations was below the limit of determination. The hierarchical structure was included in the model in order to take into account the within-batch and between-batch variability, which may have a significant impact on the sample outcome depending on the sampling plan. Temporal changes in the prevalence of campylobacter were modeled using a Markovian time series. The proposed model is adaptable for other pathogens if the same type of data set is available. The computation of the model was performed using OpenBUGS software. PMID- 26857999 TI - Community health worker-based intervention for adherence to drugs and lifestyle change after acute coronary syndrome: a multicentre, open, randomised controlled trial. AB - BACKGROUND: Adherence to drugs and healthy lifestyles is low after acute coronary syndrome. We assessed whether trained community health workers could improve adherence to drugs, lifestyle changes, and clinical risk markers in patients with acute coronary syndrome in India. METHODS: In this study done at 14 hospitals in India we randomly assigned (1:1) patients with acute coronary syndrome 1 or 2 days before discharge from hospital to a community health worker-based intervention group or a standard care group. Patients were randomly assigned with a telephone randomisation service. In the intervention group, during four in hospital and two home visits, community health workers used unstructured discussions, visual methods, and patient diaries to educate patients on healthy lifestyle and drugs, and measures to enhance adherence. The primary outcome was adherence to proven secondary prevention drugs (antiplatelet drugs, beta blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and statins) estimated using a Composite Medication Adherence Scale at 1 year. The secondary outcomes were difference in lifestyle factors (diet, exercise, and tobacco and alcohol use), and clinical risk markers (blood pressure, bodyweight, BMI, heart rate, and lipids). All analyses were by intention to treat. This trial is registered with the Clinical Trial Registry of India, number REF/2013/03/004737, and ClinicalTrials.gov, number NCT01207700. RESULTS: Between Aug 23, 2011, and June 25, 2012, 806 participants were randomly assigned (405 to a community health worker-based intervention group and 401 to a standard care group). At 1 year, 40 patients had died and 15 had discontinued or been lost to follow-up, so 750 (93%) were included in the analyses (375 in each group). Secondary prevention drugs prescribed at discharge were 98% (786/803) for any antiplatelet drug, 79% (638/803) for dual antiplatelet drugs, 69% (555/803) for beta blockers, 69% (552/803) for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and 95% (762/803) for statins. At one year, overall adherence (>=80%) to prescribed evidence-based drugs was higher in the intervention group than in the control group (97% vs 92%, odds ratio [OR] 2.62, 95% CI 1.32-5.19; p=0.006). For individual drugs, we recorded significant differences for angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (97% [233/240] in the intervention group vs 93% [223/240] in the control group; p=0.036) and statins (97% [346/356] vs 93% [321/345]; p=0.011). The intervention group had significantly greater adherence to smoking cessation (85% [110/129] vs 52% [71/138], OR 5.46, 95% CI 3.03-9.86; p<0.0001), regular physical activity (89% [333/375] vs 60% [226/375], OR 5.23, 95% CI 3.57-7.66; p<0.0001), and healthy diet (score 5.0 vs 3.0, OR 2.47, 95% CI 1.88-3.25; p<0.0001). More patients in the intervention group had stopped alcohol use at 1 year (87% [64/74] vs 46% [46/67], OR 2.92, 95% CI 1.26-6.79; p =0.010). At 1 year, the mean systolic blood pressure (124.4 mm Hg [SD 13.5] vs 128.0 mm Hg [15.9]; p=0.002), weight (65.0 kg [11.0] vs 66.5 kg [11.5]; p<0.0001), cholesterol (157.0 [40.2] vs 166.9 [48.4]; p=0.184), LDL (81.0 [20.6] vs 87.3 [29.9]; p=0.191), HDL (42.0 [11.4] vs 38.2 [6.5]; p=0.042), and BMI (24.4 kg/m(2) [SD 3.7] vs 25.0 kg/m(2) [3.8]; p<0.0001) were lower in the intervention group than in the control group. However, we noted no significant difference in diastolic blood pressure and heart rate. INTERPRETATION: A community health worker-based personalised intervention strategy in patients with acute coronary syndrome improved adherence to evidence based drugs and healthy lifestyles, and resulted in an improvement in clinical risk markers. Integration of trained community health workers can improve secondary prevention in coronary artery disease. FUNDING: US National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, Department of Health and Human Services, and the UnitedHealth group, USA. PMID- 26858001 TI - Different morphologic formation patterns of dark patches in the black-spotted frog (Pelophylax nigromaculata) and the Asiatic toad (Bufo gargarizans). AB - The black-spotted frog (Pelophylax nigromaculata) and Asiatic toad (Bufo gargarizans), two relatively distantly related species, live in different habitats with different adaptive dark patches. To explain the formation of dark patches, the distribution patterns of melanin granules were examined with light microscopy and transmission electron microscopy. Melanin granules were produced and gathered into the "cap" structures on top of the nuclei in most epidermal cells. The "cap" structures may play a role in forming the dorsal dark patches coupled with three-layer melanophores, which can give rise to three layers of interconnected melanin networks in the dorsal dermis in P. nigromaculata. Epidermal melanocytes are rare and do not have a definitive role in forming dorsal dark patches in either P. nigromaculata or B. gargarizans. In B. gargarizans, the dermal melanophores only give rise to a single-layered melanin network, which hardly results in dark patches in the dorsal skin. However, the dermal melanophores migrate twice and form into pseudostratified networks, leading to dark patch formation in the ventral skin in B. gargarizans. The melanin granules precisely coregulate dark patches in the dermis and/or epidermis in P. nigromaculata and B. gargarizans. The dark patch formation depends on melanin granules in the epidermis or/and dermis in P. nigromaculata and B. gargarizans. PMID- 26858003 TI - Optimization of cellulase-assisted extraction process and antioxidant activities of polysaccharides from Tricholoma mongolicum Imai. AB - BACKGROUND: Tricholoma mongolicum Imai is a well-known edible and medicinal mushroom which in recent years has attracted increasing attention because of its bioactivities. In this study, water-soluble polysaccharides were extracted from T. mongolicum Imai by cellulase-assisted extraction and their antioxidant activities were investigated. RESULTS: In order to improve the yield of polysaccharides, four variables, cellulase amount (X1 ), pH (X2 ), temperature (X3 ) and extraction time (X4 ), were investigated with a Box-Behnken design. The optimal conditions were predicted to be cellulase amount of 20 g kg(-1) , pH of 4.0, temperature of 50 degrees C and extraction time of 127 min, with a predicted polysaccharide yield of 190.1 g kg(-1) . The actual yield of polysaccharides under these conditions was 189.6 g kg(-1) , which matched the predicted value well. The crude polysaccharides were purified to obtain four fractions, and characterization of each was carried out. In addition, antioxidant properties of four polysaccharides assessed by 1,1-diphenyl-2-picryldydrazyl (DPPH) and hydroxyl radical-scavenging assays indicated that polysaccharides from T. mongolicum Imai (TMIPs) possessed antioxidant activity in a dose-dependent manner. CONCLUSION: TMIPs show moderate antioxidant activities in vitro. Therefore it is suggested that TMIPs are potential natural antioxidants for use in functional foods. (c) 2016 Society of Chemical Industry. PMID- 26858004 TI - GIbPSs: a toolkit for fast and accurate analyses of genotyping-by-sequencing data without a reference genome. AB - Genotyping-by-sequencing (GBS) and related methods are increasingly used for studies of non-model organisms from population genetic to phylogenetic scales. We present GIbPSs, a new genotyping toolkit for the analysis of data from various protocols such as RAD, double-digest RAD, GBS, and two-enzyme GBS without a reference genome. GIbPSs can handle paired-end GBS data and is able to assign reads from both strands of a restriction fragment to the same locus. GIbPSs is most suitable for population genetic and phylogeographic analyses. It avoids genotyping errors due to indel variation by identifying and discarding affected loci. GIbPSs creates a genotype database that offers rich functionality for data filtering and export in numerous formats. We performed comparative analyses of simulated and real GBS data with GIbPSs and another program, pyRAD. This program accounts for indel variation by aligning homologous sequences. GIbPSs performed better than pyRAD in several aspects. It required much less computation time and displayed higher genotyping accuracy. GIbPSs retained smaller numbers of loci overall in analyses of real GBS data. It nevertheless delivered more complete genotype matrices with greater locus overlap between individuals and greater numbers of loci sampled in all individuals. PMID- 26858002 TI - Evolutionary history of double-stranded RNA binding proteins in plants: identification of new cofactors involved in easiRNA biogenesis. AB - In this work, we retrace the evolutionary history of plant double-stranded RNA binding proteins (DRBs), a group of non-catalytic factors containing one or more double-stranded RNA binding motif (dsRBM) that play important roles in small RNA biogenesis and functions. Using a phylogenetic approach, we show that multiple dsRBM DRBs are systematically composed of two different types of dsRBMs evolving under different constraints and likely fulfilling complementary functions. In vascular plants, four distinct clades of multiple dsRBM DRBs are always present with the exception of Brassicaceae species, that do not possess member of the newly identified clade we named DRB6. We also identified a second new and highly conserved DRB family (we named DRB7) whose members possess a single dsRBM that shows concerted evolution with the most C-terminal dsRBM domain of the Dicer-like 4 (DCL4) proteins. Using a BiFC approach, we observed that Arabidopsis thaliana DRB7.2 (AtDRB7.2) can directly interact with AtDRB4 but not with AtDCL4 and we provide evidence that both AtDRB7.2 and AtDRB4 participate in the epigenetically activated siRNAs pathway. PMID- 26858006 TI - A new case of malonyl-CoA decarboxylase deficiency with mild clinical features. AB - Malonyl-CoA decarboxylase deficiency is an extremely rare autosomal recessive inborn error of fatty acid metabolism. It usually follows a severe disease course and presents poor prognosis without treatment. Here, we report an affected female juvenile with a mild clinical and biochemical phenotype who mainly featured poor schooling without cardiomyopathy and metabolic acidosis. She was suspected of malonyl-CoA decarboxylase deficiency due to a 57-kb deletion in 16q23.3 encompassing the MLCYD gene revealed by chromosome microarray. Malonyl-CoA decarboxylase deficiency was then confirmed by acylcarnitine analysis and organic acid analysis. Real-time PCR analysis of the patient revealed the first three exon deletion of the MLYCD gene, which was maternally inherited. DNA sequencing of the MLYCD gene of the patient identified a novel heterozygous mutation (c.911G>A, p.G304E) in exon 4 that was paternally inherited. The patient urine malonic acid dissolved and had a better school record in 6 month after initiation of fat-limited diet. At 1 year post treatment, the blood malonylcarnitine level decreased remarkably. Our result expands the phenotype of malonyl-CoA decarboxylase deficiency and suggests attentions should be paid to the mild form of disorders, for example, malonyl-CoA decarboxylase deficiency, which usually present a severe disease course. PMID- 26858007 TI - Colour quantitation for chemical spot tests for a controlled substances presumptive test database. AB - Crime scene investigators (CSIs) often encounter unknown powders, capsules, tablets, and liquids at crime scenes, many of which are controlled substances. Because most drugs are white powders, however, visual determination of the chemical identity is difficult. Colourimetric tests are a well-established method of presumptive drug identification. Positive tests are often reported differently, however, because two analysts may perceive colour or record colourimetric results in different ways. In addition to perceiving colour differently, it is very common for there to be poor visibility conditions (e.g. rain, darkness) while performing these tests, further obscuring the results. In order to address these concerns and to create uniformity in the reporting of on site colourimetric test results, this study has evaluated two of the state-of-the art apps (ColorAssist(r) and Colorimeter(r)) for reporting the colour test results quantitatively in red-green-blue (RGB) format. The compiled library database of presumptive test results contains over 3300 data points including over 800 unique drug/test combinations. Variations observed between test replicates, from performing a test on different days, recording with a different device type (e.g. iPod Touch, iPhone models 4, 5c, 5s, or 6), and using different quantities of drug are discussed. Overall, the least variation in Euclidian norm was observed using ColorAssist(r) with the camera light (25.1+/-22.1) while the variation between replicates and data recorded using different devices was similar. The resulting library is uploaded to a smartphone application aimed to aid in identifying and interpreting suspected controlled substance evidence. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26858005 TI - Chronic Alcohol Consumption Causes Liver Injury in High-Fructose-Fed Male Mice Through Enhanced Hepatic Inflammatory Response. AB - BACKGROUND: Obesity and the metabolic syndrome occur in approximately one-third of patients with alcoholic liver disease (ALD). The increased consumption of fructose parallels the increased prevalence of obesity and the metabolic syndrome in the United States and worldwide. In this study, we investigated whether dietary high fructose potentiates chronic alcohol-induced liver injury, and explored potential mechanism(s). METHODS: Six-week-old male C57BL/6J mice were assigned to 4 groups: control, high fructose, chronic ethanol (EtOH), and high fructose plus chronic alcohol. The mice were fed either control diet or high fructose diet (60%, w/w) for 18 weeks. Chronic alcohol-fed mice were given 20% (v/v) ethanol (Meadows-Cook model) ad libitum as the only available liquid from the 9th week through the 18th week. Liver injury, steatosis, hepatic inflammatory gene expression, and copper status were assessed. RESULTS: High-fructose diet and chronic alcohol consumption alone each induce hepatic fat accumulation and impair copper status. However, the combination of dietary high fructose plus chronic alcohol synergistically induced liver injury as evidenced by robustly increased plasma alanine aminotransferase and aspartate aminotransferase, but the combination did not exacerbate hepatic fat accumulation nor worsen copper status. Moreover, FE-fed mice were characterized by prominent microvesicular steatosis. High-fructose diet and chronic alcohol ingestion together led to a significant up regulation of Kupffer cell (KC) M1 phenotype gene expression (e.g., tumor necrosis factor-alpha and monocyte chemoattractant protein-1), as well as Toll like receptor 4 (TLR4) signaling gene expression, which is also associated with the up-regulation of KCs and activation marker gene expression, including Emr1, CD68, and CD163. CONCLUSIONS: Our data suggest that dietary high fructose may potentiate chronic alcohol consumption-induced liver injury. The underlying mechanism might be due to the synergistic effect of dietary high fructose and alcohol on the activation of the TLR4 signaling pathway, which in turn leads to KC activation and phenotype switch toward M1 polarization. This study suggests that alcohol-fructose combination contributes to ALD progression. PMID- 26858008 TI - Patient Experience Assessment is a Requisite for Quality Evaluation: A Discussion of the In-Center Hemodialysis Consumer Assessment of Health Care Providers and Systems (ICH CAHPS) Survey. AB - Patient experience surveys provide a critical and unique perspective on the quality of patient-centered healthcare delivery. These surveys provide a mechanism to systematically express patients' voice on topics valued by patients to make decisions about choices in care. They also provide an assessment to healthcare organizations about their service that cannot be obtained from any other source. Regulatory agencies have mandated the assessment of patients' experience as part of healthcare value based purchasing programs and weighted the results to account for up to 30% of the total scoring. This is a testimony to the accepted importance of this metric as a fundamental assessment of quality. After more than a decade of rigorous research, there is a significant body of growing evidence supporting specifically the validity and use of the Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys, including a version specific to in-center hemodialysis (ICH CAHPS). This review will focus on the ICH CAHPS survey including a review of its development, content, administration, and also a discussion of common criticisms. Although it is suggested that the survey assesses activities and experiences that are not modifiable by the healthcare organization (or the dialysis facility in our case) emerging evidence suggests otherwise. Dialysis providers have an exclusive opportunity to lead the advancement of understanding the implications and serviceability of the evaluation of the patient experience in health care. PMID- 26858009 TI - Evolution of human cytomegalovirus-seronegative donor/-seropositive recipient high-risk combination frequency in allogeneic hematopoietic stem cell transplantations at Institute of Hematology and Blood Transfusion during 1995 2014. AB - BACKGROUND: Human cytomegalovirus (HCMV) establishes lifelong latent infection that can result in severe life-threatening disease in immunosuppressed patients after hematopoietic stem cell transplantation (HSCT). An HCMV-seropositive transplant recipient who receives a graft from a seronegative donor (R+/D-) is at high risk of recurrent HCMV reactivation. METHODS: To assess the incidence of R+/D- combination, we retrospectively evaluated HCMV-seronegative donors for 746 allogeneic HSCT treatments carried out at our center during 1995-2014. In our cohort, 20% HCMV-seronegative HSCT recipients, 21% HCMV-seronegative related graft donors, and 52% HCMV-seronegative unrelated graft donors were included. RESULTS: Analyses of the HCMV serostatus of hematopoietic stem cell donors during 2 consecutive calendar periods (1995-2005 and 2006-2014) showed a significant increase in the proportion of seronegative donors (odds ratio [OR] = 1.947). In addition, the number of HSCT treatments using an unrelated donor increased (OR = 2.376). Finally, the use of grafts from countries with a very low HCMV prevalence increased. CONCLUSION: This increase in HCMV seronegativity in unrelated donors and the increased proportion of unrelated donors were responsible for the increased occurrence of the high-risk combination R+/D- (OR = 1.680). If the reduction in the rate of HCMV-seropositive graft donors continues, an increased frequency of HCMV reactivation events in our transplant recipients can be expected, because of the increasing occurrence of the high-risk R+/D- combination. PMID- 26858010 TI - Development of a conceptual policy framework for advanced practice nursing: an ethnographic study. AB - AIM: To report on a study examining policy development for advanced practice nursing from intent of policy to realization in practice. BACKGROUND: Inclusion of advanced practice nursing roles in the healthcare workforce is a worldwide trend. Optimal advanced nursing practice requires supportive policies. Little is known about how policy is developed and implemented. DESIGN: Ethnography using an instrumental case study approach was selected to give an in-depth understanding of the experiences of one country (Singapore) to contribute to insight into development elsewhere. METHODS: The four-phase study was conducted from 2008-2012 and included document analysis (n = 47), interviews with key policy decision makers (n = 12), interviews with nursing managers and medical directors (n = 11), interviews and participant observation with advanced practice nurses (n = 15). RESULTS: Key policymakers in positions of authority were able to promote policy development. However, this was characterized by lack of strategic planning for implementation. A vague understanding by nursing managers and medical directors of policies, the role and its position in the healthcare workforce led to indecision and uncertainty in execution. Advanced practice nurses developed their role based on theory acquired in their academic programme but were unsure what role to assume in practice. Lack of clear guidelines led to unanticipated difficulties for institutions and healthcare systems. CONCLUSION: Strategic planning could facilitate integration of advanced practice nurses into the healthcare workforce. A Conceptual Policy Framework is proposed as a guide for a coordinated approach to policy development and implementation for advanced practice nursing. PMID- 26858011 TI - Converting bulk sugars into prebiotics: semi-rational design of a transglucosylase with controlled selectivity. AB - Despite the growing importance of prebiotics in nutrition and gastroenterology, their structural variety is currently still very limited. The lack of straightforward procedures to gain new products in sufficient amounts often hampers application testing and further development. Although the enzyme sucrose phosphorylase can be used to produce the rare disaccharide kojibiose (alpha-1,2 glucobiose) from the bulk sugars sucrose and glucose, the target compound is only a side product that is difficult to isolate. Accordingly, for this biocatalyst to become economically attractive, the formation of other glucobioses should be avoided and therefore we applied semi-rational mutagenesis and low-throughput screening, which resulted in a double mutant (L341I_Q345S) with a selectivity of 95% for kojibiose. That way, an efficient and scalable production process with a yield of 74% could be established, and with a simple yeast treatment and crystallization step over a hundred grams of highly pure kojibiose (>99.5%) was obtained. PMID- 26858012 TI - Effects of Supplementing Holstein Heifers with Dietary Melatonin during Late Gestation on Growth and Cardiovascular Measurements of their Offspring. AB - The objective was to examine the effects of supplementing dams with dietary melatonin during late gestation on offspring growth and cardiovascular measurements. On day 190 of gestation, heifers (n = 20) were blocked by body weight and randomly assigned to one of two dietary treatments consisting of 20 mg of dietary melatonin per day [melatonin (MEL)] or no melatonin supplementation [control (CON)]. Dietary treatments were terminated on day 262 of gestation. At birth, calves were separated from their dams with no further treatments. Calf (n = 18) blood pressure, cortisol, nitrites and total antioxidant capacity were collected on weeks 0, 1, 2, 3 and 4 of age. Calf hepatic portal blood flow and concentrations of insulin-like growth factor 1 were determined on weeks 0 and 4 of age. Calf body weight, abdominal girth, hip height and wither height increased (p < 0.05) with age. An age by treatment interaction (p < 0.01) was observed for calf body weight, which was increased at weeks 8 and 9 of age in calves born to MEL heifers compared to calves born to CON heifers. Pulse pressure, mean arterial pressure, absolute hepatic portal blood flow and blood flow relative to calf body weight were not different (p > 0.05) between treatments. A main effect of calf age (p < 0.05) was observed for concentrations of insulin-like growth factor 1, which was decreased at week 4 compared to week 0. An age by treatment interaction (p < 0.05) was observed for cortisol, which was decreased at week 2 in calves from MEL-treated dams compared to calves from CON-treated dams. Early post-natal growth was altered in offspring born to dams supplemented with dietary melatonin. This could lead to further foetal programming implications in conjunction with post-natal development. PMID- 26858013 TI - Effects of Nintendo Wii-Fit(r) video games on balance in children with mild cerebral palsy. AB - BACKGROUND: This study compared the effects of Nintendo Wii-Fit(r) balance-based video games and conventional balance training in children with mild cerebral palsy (CP). METHODS: This randomized controlled trial involved 30 ambulatory pediatric patients (aged 5-18 years) with CP. Participants were randomized to either conventional balance training (control group) or to Wii-Fit balance-based video games training (Wii group). Both group received neuro-developmental treatment (NDT) during 24 sessions. In addition, while the control group received conventional balance training in each session, the Wii group played Nintendo Wii Fit games such as ski slalom, tightrope walk and soccer heading on balance board. Primary outcomes were Functional Reach Test (forward and sideways), Sit-to-Stand Test and Timed Get up and Go Test. Nintendo Wii Fit balance, age and game scores, 10 m walk test, 10-step climbing test and Wee-Functional Independence Measure (Wee FIM) were secondary outcomes. RESULTS: After the treatment, changes in balance scores and independence level in activities of daily living were significant (P < 0.05) in both groups. Statistically significant improvements were found in the Wii-based game group compared with the control group in all balance tests and total Wee FIM score (P < 0.05). CONCLUSION: Wii-fit balance based video games are better at improving both static and performance-related balance parameters when combined with NDT treatment in children with mild CP. PMID- 26858015 TI - Spectral background from commercially available D2 O: an important consideration for trace analysis using cryoprobes. PMID- 26858016 TI - Impact of obesity and diabetes on waitlist survival, probability of liver transplantation and post-transplant survival among chronic hepatitis C virus patients. AB - BACKGROUND & AIMS: The rising prevalence of obesity and diabetes mellitus (DM) among hepatitis C virus (HCV) patients contributes to concurrent nonalcoholic fatty liver disease (NAFLD). We aim to evaluate the impact of concurrent obesity or DM on waitlist survival and probability of liver transplantation (LT) among adults with chronic HCV awaiting LT. METHODS: Using 2003-2013 United Network for Organ Sharing data, we evaluated the impact of obesity and DM among adults with chronic HCV awaiting LT: non-obese, non-DM vs. obese, non-DM (obese) vs. non obese, DM (DM) vs. obese and DM. Overall, LT waitlist survival and probability of receiving LT were evaluated using Kaplan-Meier and multivariate logistic regression models. RESULTS: From 2003-2013, there were 43 478 new LT waitlist registrants with chronic HCV (21.0% with HCC, 79% without HCC). Obesity was associated with lower probability of receiving LT (OR, 0.91; 95% CI, 0.85-0.97; P < 0.01), and lower probability of waitlist mortality (OR, 0.80; 95% CI, 0.72 0.89; P < 0.001) when compared to non-obese patients. DM among HCV patients did not impact probability of waitlist survival or receiving LT. When evaluating post LT survival, compared to non-obese, non-DM patients, obese HCV patients had significantly lower post-LT mortality (HR 0.86; 95%CI, 0.81-0.92; P < 0.001); whereas, HCV patients with DM had significantly higher post-LT mortality (HR, 1.22; 95% CI, 1.12-1.33; P < 0.001). CONCLUSION: Among adults with chronic HCV awaiting LT in the US, obesity is associated with lower probability of receiving LT, but did not impact waitlist survival. DM among chronic HCV patients did not impact waitlist survival or probability of LT. PMID- 26858014 TI - American Thyroid Association Statement on Remote-Access Thyroid Surgery. AB - BACKGROUND: Remote-access techniques have been described over the recent years as a method of removing the thyroid gland without an incision in the neck. However, there is confusion related to the number of techniques available and the ideal patient selection criteria for a given technique. The aims of this review were to develop a simple classification of these approaches, describe the optimal patient selection criteria, evaluate the outcomes objectively, and define the barriers to adoption. METHODS: A review of the literature was performed to identify the described techniques. A simple classification was developed. Technical details, outcomes, and the learning curve were described. Expert opinion consensus was formulated regarding recommendations for patient selection and performance of remote-access thyroid surgery. RESULTS: Remote-access thyroid procedures can be categorized into endoscopic or robotic breast, bilateral axillo-breast, axillary, and facelift approaches. The experience in the United States involves the latter two techniques. The limited data in the literature suggest long operative times, a steep learning curve, and higher costs with remote-access thyroid surgery compared with conventional thyroidectomy. Nevertheless, a consensus was reached that, in appropriate hands, it can be a viable option for patients with unilateral small nodules who wish to avoid a neck incision. CONCLUSIONS: Remote access thyroidectomy has a role in a small group of patients who fit strict selection criteria. These approaches require an additional level of expertise, and therefore should be done by surgeons performing a high volume of thyroid and robotic surgery. PMID- 26858017 TI - Imparting Nonfouling Properties to Chemically Distinct Surfaces with a Single Adsorbing Polymer: A Multimodal Binding Approach. AB - Surface-active polymers that display nonfouling properties and carry binding groups that can adsorb onto different substrates are highly desirable. We present a postmodification protocol of an active-ester-containing polymer that allows the creation of such a versatile platform. Poly(pentafluorophenyl acrylate) has been postmodified with a fixed grafting ratio of a nonfouling function (mPEG) and various combinations of functional groups, such as amine, silane and catechol, which can provide strong affinity to two model substrates: SiO2 and TiO2 . Adsorption, stability and resistance to nonspecific protein adsorption of the polymer films were studied. A polymer was obtained that maintained its surface functionality under a variety of harsh conditions. EG surface-density calculations show that this strategy generates a denser packing when both negatively and positively charged groups are present within the backbone, and readily allows the fabrication of a broad combinatorial matrix. PMID- 26858020 TI - Reply to the letter regarding the article "Incidence, determinants and prognostic relevance of cardiogenic shock in Takotsubo cardiomyopathy". PMID- 26858019 TI - What is cholera? A preliminary study on caretakers' knowledge in Bangladesh. AB - BACKGROUND: Cholera has afflicted the Indian sub-continent for centuries, predominantly in West Bengal and modern-day Bangladesh. This preliminary study aims to understand the current level of knowledge of cholera in female Bangladeshi caretakers, which is important in the outcome of the disease and its spread. A pilot study was conducted among 85 women in Bangladesh using qualitative questionnaires to explore the ability of female caretakers in identifying cholera and its transmission. FINDINGS: The survey revealed that though all the female caretakers were aware of the term "cholera," nearly a third of the respondents did not associate diarrhea with cholera or mentioned symptoms that could not be caused by cholera (29 %). Approximately half of the respondents associated water with the cause of cholera (56 %) and only 8 % associated cholera with sanitation or hygiene. Shame and stigma (54 %) were more commonly described than death (47 %) as negative effects of cholera. CONCLUSIONS: The results from this study are suggestive of a need for reformulation of cholera and diarrhea communication. Messaging should be based on signs of dehydration, foregoing the use of medical terminology. PMID- 26858018 TI - Plasmodium falciparum drug resistance in Angola. AB - Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to consolidate malaria control, while preparing for the elimination of the disease, along with others African countries in the region. However, the remarkable capacity of Plasmodium to develop drug resistance represents an alarming threat for those achievements. Herein, the available, but relatively scarce and dispersed, information on malaria drug resistance in Angola, is reviewed and discussed. The review aims to inform but also to encourage future research studies that monitor and update the information on anti-malarial drug efficacy and prevalence of molecular markers of drug resistance, key fields in the context and objectives of elimination. PMID- 26858021 TI - Surgical management of an anomalous right coronary artery. AB - Anomalous aortic origin of coronary arteries is a rare congenital heart disease that can be associated with sudden death. We present the case of a young patient who sustained a cardiac arrest revealing an anomalous origin of the right coronary artery. Unroofing and pericardial enlargement of the coronary artery ostia was performed and the patient is actually asymptomatic. PMID- 26858022 TI - Erratum to: ADAMTS-4 promotes neurodegeneration in a mouse model of amyotrophic lateral sclerosis. PMID- 26858023 TI - Adult hookworms (Necator spp.) collected from researchers working with wild western lowland gorillas. AB - BACKGROUND: In general, studies on the diversity of strongylid nematodes in endangered host species are complicated as material obtained by non-invasive sampling methods has limited value for generic and species identification. While egg morphology barely allows assignment to family, the morphology of cultivated infective third stage larvae provides a better resolution at the generic level but cannot be used for exact species identification. Morphology-based taxonomic approaches greatly depend on the examination of adult worms that are usually not available. METHODS: Hookworm parasites in two European researchers, who participated in gorilla research in the Central African Republic, were expelled after anthelmintic treatment to the faeces, collected and morphologically examined. A male worm discharged naturally from a wild bonobo (Pan paniscus) in Congo was also examined for comparison. RESULTS: Two species of Necator were identified in researchers' faecal material: Necator americanus (Stiles, 1902) and N. gorillae Noda & Yamada, 1964; the latter species differed in having a smaller body, smaller buccal cavity and shorter spicules with spade-shaped membranes situated distally. Males of N. gorillae also possessed unusual cuticular thickenings on the dorsal side of the prebursal region of the body. These characters, shared with the male worm from the bonobo, correspond well to the description of N. gorillae described from gorillas in Congo. CONCLUSIONS: Based on the morphology of the hookworms recovered in this study and previous molecular analyses of larvae developed from both humans and western lowland gorillas (Gorilla gorilla gorilla) from this locality, we conclude that the researchers became infected with gorilla hookworms during their stay in the field. This is the first report of infection with a Necator species other than N. americanus in humans. PMID- 26858024 TI - Ultrasound-assisted preparation of novel ibuprofen-loaded excipient with improved compression and dissolution properties. AB - CONTEXT: Most of the active pharmaceutical ingredients (APIs) suffer from a drawback of poor aqueous solubility. In addition to the same, some APIs show poor tabletting behavior creating problems in formulation development. Crystal engineering can be an efficient tool in rectification of such problems associated with the APIs. Thus present work deals with crystallization of ibuprofen (a model drug) onto the surface of dicalcium phosphate (DCP) particles using different techniques. OBJECTIVE: The objective of the present work was to prepare ibuprofen loaded DCP particles and further to analyze them for compressibility and dissolution behavior. MATERIALS AND METHODS: Various crystallization techniques such as solvent evaporation (SE), melt crystallization (MC), melt sonocrystallization (MSC), antisolvent crystallization (AC), and antisolvent sonocrystallization (ASC) were screened for the preparation of ibuprofen-loaded DCP. Products obtained from different techniques were analyzed for physicochemical, micromeritic and compression properties. RESULTS AND DISCUSSION: ASC technique was found to be suitable for preparing directly compressible ibuprofen-loaded DCP particles. The change in the crystal habit (needle to plate shape) of ibuprofen and its crystallization in miniscular form onto the surface of DCP particles showed significant improvement in the dissolution rate and compression properties of ibuprofen due to an increase in specific surface area when compared with ibuprofen crystallized by other techniques. Additionally, the tablets prepared from ASC powder did not require binder since ibuprofen acted as melt binder during compression. CONCLUSION: Directly compressible ibuprofen loaded DCP particles can serve as an alternative for conventional ibuprofen tablets prepared by wet granulation technique. PMID- 26858026 TI - Rituximab is an effective and safe treatment of relapse in elderly patients with resistant warm AIHA. AB - We evaluated the efficacy and safety of rituximab for the treatment of 23 elderly patients (median age 78 years) with warm autoimmune haemolytic anaemia (AIHA). The median follow-up was 31 months. Patients had received one to five previous treatments. Rituximab was administered by intravenous infusion at a dose of 375 mg/m(2) once weekly for 4 weeks. The OR rate was 86.9 % (CR = 39.1 %, PR = 47.8 %). Median OS was 87 months. The median OS of patients who reached CR could not be calculated, and that of patients with PR was 67 months. At last follow-up, eight of the 20 responding patients, including one patient in CR and seven in PR, had relapsed after a median of 6 months. Failure to achieve CR was a risk factor for relapse (p = 0.028). We did not identify any pretreatment characteristics predictive of response to rituximab. In conclusion, rituximab is an effective treatment for elderly patients with refractory warm AIHA. PMID- 26858027 TI - Purification of hematopoietic stem cells from bone marrow. AB - Lifelong production of blood cells is sustained by hematopoietic stem cells (HSC) which reside at a very low frequency within the bone marrow (BM). The use of flow cytometry has been critical in establishing methods to isolate and characterize HSCs and their progenitors. For more than 30 years, researchers have uncovered many novel markers that when used in combination significantly enhance the purification of HSCs from murine and human bone marrow. Here, we review the phenotypic markers and strategies used to purify HSCs. PMID- 26858028 TI - Evaluation of clinicopathologic characteristics and the BRAF V600E mutation in Erdheim-Chester disease among Chinese adults. AB - Erdheim-Chester disease (ECD) is a rare form of histiocytosis with a broad, non specific clinical spectrum. Here, we retrospectively evaluated the clinical and pathologic characteristics, presence of the BRAF V600E mutation, treatment options, and outcomes of Chinese patients diagnosed with ECD at our center. Patients diagnosed with ECD between January 2010 and April 2015 at Peking Union Medical College Hospital were included for study. We evaluated baseline characteristics, reviewed histological material, and tested for the presence of the BRAF V600E mutation using immunohistochemistry and polymerase chain reaction (PCR). Sixteen patients were diagnosed with ECD. Median disease duration (from the first symptom to diagnosis) was 22.5 months (range, 3-100 months). The main sites of involvement included bone (93.8 %), cardiovascular region (43.8 %), skin (31.3 %), central nervous system (25 %), and "hairy kidney" (25 %). The BRAF V600E mutation was detected in 68.8 % patients using PCR and 50 % patients with immunohistochemistry. Three patients could not be diagnosed using histological analysis owing to similarities with Rosai-Dorfman disease, and diagnosis in these cases was confirmed based on the BRAF V600E mutation status. Ten patients (62.5 %) received IFN-alpha as first-line treatment. Thirteen patients (81.3 %) were still alive at median follow-up of 14.5 months. ECD remains a largely overlooked disease, and increased recognition by clinicians and pathologists is necessary for effective diagnosis and treatment. The presence of the BRAF V600E mutation may facilitate discrimination of ECD from other non-Langerhans cell histiocytoses. PMID- 26858031 TI - The Need for an Ecological Approach to Parental Stress in Autism Spectrum Disorders: The Combined Role of Individual and Environmental Factors. AB - This study aimed to identify parental stress predictors in ASD by considering individual and environmental factors in an ecological approach. Participants were 115 parents of children with ASD aged from 3 to 10 years. Multiple regression analyses were conducted to determine the best predictors of parental stress among child-related, parent-related and environmental factors. Poor quality interactions within the extended family, high levels of expressed emotion and absence of children's schooling were associated with higher stress, regardless of the child's age and developmental quotient [F (3) = 37.051; p < 0.001; Adj. R(2) = 0.457]. This study highlights the importance of considering environmental factors, specifically family variables, to understand parental stress. These key findings should be considered when designing support programs. PMID- 26858033 TI - Factors Mediating Dysphoric Moods and Help Seeking Behaviour Among Australian Parents of Children with Autism. AB - This study compared levels of state affect, dysphoric mood, and parenting sense of competence in Australian parents of children with or without autism. The effects of personality and location on the parents' experience were also examined, while controlling for current affect. Possible relationships among personality, location factors and help-seeking behavior were also explored in parents of children with autism. Prior findings of higher dysphoric mood levels in parents of children with autism were supported, as was the positive correlation between dysphoric moods and Neuroticism levels. Parenting Sense of Competence did not differ across locations, and there were no parent type by location interactions. Access to services among parents of a child with autism did not moderate dysphoria levels. PMID- 26858034 TI - Urban-rural differences in the uptake of new oral bisphosphonate formulations. AB - We identified significantly slower uptake, and consistently lower proportions of new oral bisphosphonate formulations dispensed in rural regions compared to urban regions of Ontario. Further research examining regional differences in outcomes may provide insight as to whether urban-rural differences in prescribing translate into health disparities between regions. PURPOSE: The aim of this study was to examine urban-rural differences in the uptake of new oral bisphosphonate formulations available on the Ontario drug formulary: alendronate + vitamin D3 (January 2007), monthly risedronate (June 2009), and risedronate delayed-release (February 2012). METHODS: We plotted the monthly proportion of new formulation claims of all claims with the same drug molecule, from their formulary listing date until March 2014. Results were stratified by major urban, nonmajor urban, and rural regions as defined by the Rurality Index of Ontario. We compared the rate of uptake over the first year of formulary availability using linear regression, and compared proportions dispensed between regions using chi-squared tests. RESULTS: We identified a regional gradient in uptake for alendronate + vitamin D3 and monthly risedronate; major urban regions had the fastest uptake, followed by nonmajor urban regions, and rural regions had the slowest uptake. Rural regions also had the slowest uptake of risedronate delayed-release; however, uptake in major urban and nonmajor urban regions were similar. Rural regions dispensed the lowest proportions for all new formulations 1 year after formulary availability: alendronate + vitamin D3 (32% major urban, 23% nonmajor urban, 12% rural), monthly risedronate (26% major urban, 21% nonmajor urban, 16% rural), and risedronate delayed-release (21% major urban, 22 % nonmajor urban, 13% rural). This pattern persisted throughout our study. CONCLUSION: We identified significantly slower uptake and lower proportions of new formulations dispensed in rural regions compared to urban regions. Further research examining regional differences in outcomes may demonstrate whether urban-rural differences in prescribing translate into health disparities between regions. PMID- 26858029 TI - The MYCN-HMGA2-CDKN2A pathway in non-small cell lung carcinoma--differences in histological subtypes. AB - BACKGROUND: Extensive research has increased our understanding of the molecular alterations needed for non-small cell lung cancer (NSCLC) development. Deregulation of a pathway including MYCN, HMGA2 and CDKN2A, with the participation of DICER1, is of importance in several solid tumours, and may also be of significance in the pathogenesis of NSCLC. METHODS: Gene expression of MYCN, HMGA2, CDKN2A and DICER1 were investigated with RT-qPCR in surgically resected NSCLC tumour tissue from 175 patients. Expression of the let-7 microRNA family was performed in 78 adenocarcinomas and 16 matching normal lung tissue samples using microarrays. The protein levels of HMGA2 were determined by immunohistochemistry in 156 tumour samples and the protein expression was correlated with gene expression. Associations between clinical data, including time to recurrence, and expression of mRNA, protein and microRNAs were analysed. RESULTS: Compared to adenocarcinomas, squamous cell carcinomas had a median 5 fold increase in mRNA expression of HMGA2 (p = 0.003). A positive correlation (r = 0.513, p < 0.010) between HMGA2 mRNA expression and HMGA2 protein expression was seen. At the protein level, 90% of the squamous cell carcinomas expressed high levels of the HMGA2 protein compared to 47% of the adenocarcinomas (p < 0.0001). MYCN was positively correlated with HMGA2 (p < 0.010) and DICER1 mRNA expression (p < 0.010), and the expression of the let-7 microRNAs seemed to be correlated with the genes studied. MYCN expression was associated with time to recurrence in multivariate survival analyses (p = 0.020). CONCLUSIONS: A significant difference in HMGA2 mRNA expression between the histological subtypes of NSCLC was seen with a higher expression in the squamous cell carcinomas. This was also found at the protein level, and we found a good correlation between the mRNA and the protein expression of HMGA2. Moreover, the expression of MYCN, HMGA2, and DICER1 seems to be correlated to each other and the expression of the let7-genes impacted by their expression. MYCN gene expression seems to be of importance in time to recurrence in this patient cohort with resected NSCLC. PMID- 26858035 TI - Hydrogenated blue titania with high solar absorption and greatly improved photocatalysis. AB - Hydrogenated black titania, with a crystalline core/amorphous shell structure, has attracted global interest due to its excellent photocatalytic properties. However, the understanding of its structure-property relationships remains a great challenge and a more effective method to produce hydrogenated titania is desirable. Herein, we report a TiH2 assisted reduction method to synthesize bluish hydrogenated titania (TiO2-x:H) that is highly crystallized. The characteristic amorphous shells, which are essential for the enhancement of solar absorption and photocatalysis in many reported hydrogenated titania, are completely removed by hydrogen peroxide. The blue TiO2-x:H sample without amorphous shells delivers not only significantly improved visible- and infrared light absorption but also greatly enhanced photocatalytic activity compared to pristine TiO2. Its water decontamination is 2.5 times faster and the hydrogen production was 1.9-fold higher over pristine TiO2. Photoelectrochemical measurement reveals greatly improved carrier density and photocurrent (a 4.3-fold increase) in the reduced TiO2-x:H samples. This work develops a facile and versatile method to prepare hydrogenated titania and proposes a new understanding of the hydrogenated titania that doped hydrogen atoms, instead of the amorphous shells, are essential for its high photocatalytic performance. PMID- 26858036 TI - Bacteriological spectrum and antimicrobial susceptibility pattern of neonatal septicaemia in a tertiary care hospital of North India. AB - BACKGROUND: Neonatal septicaemia is a clinical entity that is characterised by systemic signs and symptoms of infection and accompanied by bacteraemia in first 4 weeks of life and is one of the four leading causes of neonatal mortality and morbidity in India. AIM: To determine the bacterial spectrum and antimicrobial susceptibility pattern of neonatal septicaemia in a tertiary care hospital of North India. MATERIALS AND METHODS: In this prospective observational study, 850 blood samples were collected and processed from clinically suspected neonates according to standard laboratory protocol. Antimicrobial susceptibility of the isolates was done by Kirby Bauer disc diffusion method according to Clinical and Laboratory Standard Institution (CLSI) recommendations. RESULTS: Blood culture reports were positive in 322 (37.8%) cases. Early onset sepsis (EOS) was present in 61.41% and late onset sepsis (LOS) in 38.59% of cases. Gram-negative septicaemia (60.67%) was encountered more than Gram-positive (32.01%). Coagulase negative Staphylococci (17.43%) was the predominant isolate followed by, Klebsiella spp in 16.11% cases. Best overall sensitivity among Gram-negative isolates was to Colistin (89.94%), Imipenem (86.43%) and Meropenam (77.88%). Gram positive isolates had good (97.15%) sensitivity to linezolid, (95.23%) vancomycin and (88.57%) Teicoplanin. CONCLUSION: Gram-negative organisms are the leading cause of neonatal septicaemia with Klebsiella spp being commonest. Coagulase negative Staphylococci is the predominant isolate among Gram-positive organisms. Most of the isolates are resistant to common antibiotics. PMID- 26858038 TI - Alterations in phenolic compound levels and antioxidant activity in response to cooking technique effects: A meta-analytic investigation. AB - The aim of this study was to review prior studies that have evaluated the effects of cooking techniques on polyphenol levels and antioxidant activity in vegetables and to release a meta-analysis of the findings. Meta-analysis with a random effect model was conducted using the weighted response ratios (R*) that were calculated for each experiment. Baking (R* = 0.51), blanching (R* = 0.94), boiling (R* = 0.62), microwaving (R* = 0.54) and pressure cooking (R* = 0.47) techniques precipitated significant reductions in the polyphenol levels. Significant decreases in the antioxidant activity levels were noted after baking (R* = 0.45) and boiling (R* = 0.76), while significant increases were observed after frying (R* = 2.26) and steaming (R* = 1.52). PMID- 26858056 TI - Scleromyxedema. PMID- 26858037 TI - New insights into the Plasmodium vivax transcriptome using RNA-Seq. AB - Historically seen as a benign disease, it is now becoming clear that Plasmodium vivax can cause significant morbidity. Effective control strategies targeting P. vivax malaria is hindered by our limited understanding of vivax biology. Here we established the P. vivax transcriptome of the Intraerythrocytic Developmental Cycle (IDC) of two clinical isolates in high resolution by Illumina HiSeq platform. The detailed map of transcriptome generates new insights into regulatory mechanisms of individual genes and reveals their intimate relationship with specific biological functions. A transcriptional hotspot of vir genes observed on chromosome 2 suggests a potential active site modulating immune evasion of the Plasmodium parasite across patients. Compared to other eukaryotes, P. vivax genes tend to have unusually long 5' untranslated regions and also present multiple transcription start sites. In contrast, alternative splicing is rare in P. vivax but its association with the late schizont stage suggests some of its significance for gene function. The newly identified transcripts, including up to 179 vir like genes and 3018 noncoding RNAs suggest an important role of these gene/transcript classes in strain specific transcriptional regulation. PMID- 26858058 TI - Skin scrapings versus standardized skin surface biopsy to detect Demodex mites in patients with facial erythema of uncertain cause - a comparative study. AB - BACKGROUND: Standardized skin surface biopsy (SSSB) is considered to be the gold standard technique to evaluate the density of Demodex mites for the diagnosis of demodicidosis. Potassium hydroxide (KOH) preparation of skin scrapings is a much simpler procedure that can be used to detect pathogens in the superficial skin. OBJECTIVE: To evaluate the reliability of potassium hydroxide preparation of skin scrapings as compared to the standard skin biopsy technique with regard to capacity to detect Demodex mites, time consumed and technician satisfaction. METHODS: One hundred outpatients presenting with facial erythema of uncertain cause were enrolled. Standardized skin surface biopsy and potassium hydroxide preparation of skin scrapings were undertaken in adjacent areas on the patients' right cheek. LIMITATION: Patients with normal facial skin were excluded from the study. RESULTS: The accuracy of Demodex mite detection by potassium hydroxide preparation of skin-scrapings when compared to the standard procedure is 82%. The sensitivity, specificity, positive and negative predictive values of this method are 75%, 84.2%, 60% and 91.43%, respectively. There was no statistically significant difference between the standard and skin scraping techniques (P = 0.238) with regard to mite detection. Mean preparation time while using the skin scraping technique was 6 times less than that of the standard technique. For interpretation also, skin scraping technique (3.6 min) consumed much less time than the biopsy technique (9.8 min). Moreover, experienced technicians were more satisfied with skin scraping. CONCLUSION: Potassium hydroxide preparation of skin scrapings is an effective, time saving and practical technique to detect Demodex mites with accuracy comparable to the standard biopsy method. PMID- 26858078 TI - Limited Antigenic Diversity in Contemporary H7 Avian-Origin Influenza A Viruses from North America. AB - Subtype H7 avian-origin influenza A viruses (AIVs) have caused at least 500 confirmed human infections since 2003 and culling of >75 million birds in recent years. Here we antigenically and genetically characterized 93 AIV isolates from North America (85 from migratory waterfowl [1976-2010], 7 from domestic poultry [1971-2012], and 1 from a seal [1980]). The hemagglutinin gene of these H7 viruses are separated from those from Eurasia. Gradual accumulation of nucleotide and amino acid substitutions was observed in the hemagglutinin of H7 AIVs from waterfowl and domestic poultry. Genotype characterization suggested that H7 AIVs in wild birds form diverse and transient internal gene constellations. Serologic analyses showed that the 93 isolates cross-reacted with each other to different extents. Antigenic cartography showed that the average antigenic distance among them was 1.14 units (standard deviation [SD], 0.57 unit) and that antigenic diversity among the H7 isolates we tested was limited. Our results suggest that the continuous genetic evolution has not led to significant antigenic diversity for H7 AIVs from North America. These findings add to our understanding of the natural history of IAVs and will inform public health decision-making regarding the threat these viruses pose to humans and poultry. PMID- 26858079 TI - Management of Critical Limb Ischemia. AB - Critical limb ischemia (CLI) is a clinical syndrome of ischemic pain at rest or tissue loss, such as nonhealing ulcers or gangrene, related to peripheral artery disease. CLI has a high short-term risk of limb loss and cardiovascular events. Noninvasive or invasive angiography help determine the feasibility and approach to arterial revascularization. An endovascular-first approach is often advocated based on a lower procedural risk; however, specific patterns of disease may be best treated by open surgical revascularization. Balloon angioplasty and stenting form the backbone of endovascular techniques, with drug-eluting stents and drug coated balloons offering low rates of repeat revascularization. Combined antegrade and retrograde approaches can increase success in long total occlusions. Below the knee, angiosome-directed angioplasty may lead to greater wound healing, but failing this, any straight-line flow into the foot is pursued. Hybrid surgical techniques such as iliac stenting and common femoral endarterectomy are commonly used to reduce operative risk. Lower extremity bypass grafting is most successful with a good quality, long, single-segment autogenous vein of at least 3.5-mm diameter. Minor amputations are often required for tissue loss as a part of the treatment strategy. Major amputations (at or above the ankle) limit functional independence, and their prevention is a key goal of CLI therapy. Medical therapy after revascularization targets risk factors for atherosclerosis and assesses wound healing and new or recurrent flow-limiting disease. The ongoing National Institutes of Health-sponsored Best Endovascular Versus Best Surgical Therapy in Patients With Critical Limb Ischemia (BEST-CLI) study is a randomized trial of the contemporary endovascular versus open surgical techniques in patients with CLI. PMID- 26858081 TI - Dual Antiplatelet Therapy in Percutaneous Coronary Intervention: A Tale of 2 Decades With New Perspectives in the Era of New-Generation Drug-Eluting Stents. PMID- 26858082 TI - Pyrolysis of Plants After Phytoremediation of Contaminated Soil with Lead, Cadmium and Zinc. AB - The aim of this study was to remediate lead (Pb), cadmium (Cd) and zinc (Zn) from contaminated soil and stabilize to pyrolysis solid product. To accomplish this, phytoremediation of soil contaminated with Pb, Cd and Zn by different plants (sunflower, corn and rape) was performed with and without ethylenediaminetetraacetic acid (EDTA). According to phytoremediation results, rape was the most effective plant with 72 %, 76 % and 77 % removal efficiency for Pb, Cd and Zn, respectively. Also, EDTA addition had no significant effect on translocation of the metals from roots to stems. According to pyrolysis results, Pb, Cd and Zn in the contaminated plants were stabilized in the ash/char fraction. In addition, the solid product can be safely landfilled as inert waste since its toxicity leaching value is lower than the limit values given in the Turkish Regulation on Landfilling of Wastes. PMID- 26858080 TI - Six Versus 12 Months of Dual Antiplatelet Therapy After Implantation of Biodegradable Polymer Sirolimus-Eluting Stent: Randomized Substudy of the I-LOVE IT 2 Trial. AB - BACKGROUND: There are no reports on a large-scale randomized trial exploring optimal dual antiplatelet therapy (DAPT) duration after biodegradable polymer sirolimus-eluting stent implantation. We sought to report the outcomes of a randomized substudy of the prospective Evaluate Safety and Effectiveness of the Tivoli DES and the Firebird DES for Treatment of Coronary Revascularization (I LOVE-IT 2) trial. METHODS AND RESULTS: In the prospective noninferiority randomized I-LOVE-IT 2 trial, 1829 patients allocated to the biodegradable polymer sirolimus-eluting stent group were also randomized to receive either 6 month (n=909) or 12-month DAPT (n=920). The primary end points of this noninferiority substudy were 12-month target lesion failure (composite of cardiac death, target vessel myocardial infarction or clinically indicated target lesion revascularization), and the major secondary end points were 12-month net adverse clinical and cerebral events (composite of all-cause death, all myocardial infarction, stroke, or major bleeding [Bleeding Academic Research Consortium type >=3]). The 12-month target lesion failure in 6-month DAPT group was comparable with the 12-month DAPT group (6.8% versus 5.9%; difference and 95% confidence interval, 0.87% [-1.37% to 3.11%], P for noninferiority=0.0065). Further follow up at 18 months showed that incidence of target lesion failure and net adverse clinical and cerebral events were similar between the 2 groups (7.5% versus 6.3%, log-rank P=0.32; 7.8% versus 7.3%, log-rank P=0.60; respectively), as well as their individual end point components. CONCLUSIONS: This study indicated noninferiority in safety and efficacy of 6-month versus 12-month DAPT after implantation of a novel biodegradable polymer sirolimus-eluting stent. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01681381. PMID- 26858083 TI - Lead Concentrations in Raw Cow and Goat Milk Collected in Rural Areas of Croatia from 2010 to 2014. AB - A total of 249 cow and 33 goat milk samples were collected in rural areas of Croatia during the period 2010-2014. Lead concentrations in milk samples were analyzed by graphite furnace-atomic absorption spectroscopy. Mean Pb concentrations in milk ranged from (MUg/kg): cow 10.8-12.2; goat 9.33-60.0. The highest Pb level of 131 MUg/kg in cow milk was measured during 2014. There were no significant differences in Pb levels between cow and goat milk and also in goat milk among the analysed years. However, significant differences were found in cow milk among years. The highest Pb was determined in 2011 (157 MUg/kg in goat milk). The calculated estimated weekly intakes of Pb concentrations for cow and goat milk contribute only 1.37 % and 1.84 % to the provisional tolerable weekly intake. Therefore, the consumption of milk from both species should not pose a consumer health risk. PMID- 26858084 TI - Detection of Lead (Pb) in Three Environmental Matrices of the Cache River Watershed, Arkansas. AB - Water bodies contaminated with lead (Pb) represent a considerable threat to both human and environmental health. The Cache River, located in northeastern Arkansas has been listed as impaired on the 303(d) list due to Pb contamination. However, historical data for the watershed is limited in both sampled waterways and analyses performed. This study measures concentrations of Pb in three environmental matrices of the Cache River Watershed; dissolved in the water column, total Pb (dissolved + particulate), and sediment-bound Pb. A variety of waterways were sampled including main channel and tributary sites. Frequency of detection and mean concentrations were compared to values for the entire Lower Mississippi Watershed. In general, no significant differences were found for the CRW when compared to the LMRW, with the exception of total Pb which was detected more frequently but at lower concentrations in the CRW than in the LMRW, and sediment Pb, which was detected at a significantly lower frequency in the CRW than the LMRW. PMID- 26858086 TI - Affiliation Error in Group Information Listing. PMID- 26858085 TI - Enhancement of Proliferation and Invasion of Gastric Cancer Cell by KDM5C Via Decrease in p53 Expression. AB - Gastric cancer is a malignancy with high incidence and the second leading cause of cancer death worldwide. Development of efficient therapies against gastric cancer is urgent. Until now, the mechanisms of gastric cancer genesis remain elusive. The KDM5C is a histone demethylase that promotes cancer cell growth and is enriched in drug-resistant cancer cells. But the pathogenic breadth and mechanistic aspects of this effect relative to gastric cancer have not been defined. In present study, we found that KDM5C was overexpressed in gastric cancer cell lines and gastric cancer tissues but not in normal gastric tissues. The proliferation and invasive potential of gastric cancer cells was significantly increased by ectopic expression of KDM5C. Contrarily, RNA interference targeting KDM5C in gastric cancer cells significantly decreased the proliferation and invasive potential of cells. Moreover, we also found that the expression of p53 was modulated by KDM5C. Cells with overexpression of KDM5C exhibited greatly decreased p53 expression, whereas silencing of KDM5C expression dramatically increased p53 expression at both the messenger RNA and protein levels. Inhibition of p53 by small-interfering RNA reversed the shKDM5C-induced proliferation and invasion. Our results collectively suggested that KDM5C played a role in gastric cancer cells proliferation and invasion, which may be partly associated with the p53 expression. PMID- 26858087 TI - Risk factors for retinal detachment following cataract surgery: the impact of posterior capsular rupture. AB - AIM: To investigate risk factors for retinal detachment (RD) after cataract surgery, particularly posterior capsular rupture (PCR) with or without vitreous loss. METHODS: Single centre electronic medical record database study of 18 065 consecutive first eye cataract operations performed between 2005 and 2014. Survival analysis was performed with Kaplan-Meier curves and a Cox proportional hazard regression analysis to calculate HRs with respect to RD. RESULTS: The RD rate at 3 months and 7 years was 0.067% and 0.30%, respectively, with a median time to RD of 15 months (mean: 18 months, range: 0-84 months). Men had a higher RD risk (HR 2.00; 95% CI 1.03 to 3.88; p=0.03) in the univariate model. Patients <60 years and those >80 years had an HR of 5.12 (95% CI 2.60 to 10.07; p<0.001) and 0.16 (95% CI 0.38 to 0.69; p=0.01), respectively, compared with patients 60 80 years of age. Eyes longer than 25 mm had an HR of 3.98 (95% CI 1.93 to 8.20; p<0.001) compared with eyes 23-25 mm. PCR occurred in 400 (2.2%) eyes. The HR for RD was 12.83 (95% CI 5.62 to 29.30; p<0.001) for PCR with vitreous loss. There were no RD events in eyes with PCR without vitreous loss. CONCLUSIONS: The risk for RD after cataract surgery is higher in younger patients and eyes with longer axial length or PCR with vitreous loss during surgery. PMID- 26858088 TI - Incidence, severity and outcomes of traumatic wound dehiscence following penetrating and deep anterior lamellar keratoplasty. AB - BACKGROUND: Wound dehiscence is an uncommon but significant complication following keratoplasty. This study analysed the incidence, risk factors, clinical features and outcomes of traumatic wound dehiscence following keratoplasty. METHODS: Retrospective case series at a major tertiary care centre in New Zealand. Records of all consecutive patients who underwent penetrating keratoplasty (PK, n=1163) or deep anterior lamellar keratoplasty (DALK, n=131) between 2000 and 2014 and theatre logs were reviewed to identify all cases of traumatic dehiscence. Main outcome measures include: incidence of traumatic dehiscence, aetiology/associations and final best corrected visual acuity. RESULTS: Thirty eyes in 29 patients were identified as having a traumatic wound dehiscence following PK. No cases of wound dehiscence were identified following DALK. The incidence rate of traumatic graft dehiscence among keratoplasties performed at our centre was 2.3 per 1000 person-years. The major causes of trauma were: accidentally being struck by an object (33%) or child (13%), intentional trauma (20%) and falls (13%). Wound rupture occurred at a median of 22 months (range 6 weeks to 32 years) following keratoplasty, most frequently (37%) within the first year. Keratoplasty decompensation occurred in 17 eyes (57%). Final best corrected visual acuity was >=6/15 in 11 eyes (37%), <=6/60 in 14 eyes (47%) and no perception of light in 5 eyes (17%). CONCLUSIONS: Traumatic wound dehiscence may occur following minor trauma, even years after PK and frequently causes severe vision loss. Patients should be advised of this longer term risk and protective eye-wear should be encouraged by eye care providers. PMID- 26858090 TI - Transvaginal mesh or grafts compared with native tissue repair for vaginal prolapse. AB - BACKGROUND: A wide variety of grafts have been introduced with the aim of improving the outcomes of traditional native tissue repair (colporrhaphy) for vaginal prolapse. OBJECTIVES: To determine the safety and effectiveness of transvaginal mesh or biological grafts compared to native tissue repair for vaginal prolapse. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, ongoing trials registers, and handsearching of journals and conference proceedings (6 July 2015). We also contacted researchers in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing different types of vaginal repair (mesh, biological graft, or native tissue). DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed risk of bias, and extracted data. The primary outcomes were awareness of prolapse, repeat surgery, and recurrent prolapse on examination. MAIN RESULTS: We included 37 RCTs (4023 women). The quality of the evidence ranged from very low to moderate. The main limitations were poor reporting of study methods, inconsistency, and imprecision. Permanent mesh versus native tissue repairAwareness of prolapse at one to three years was less likely after mesh repair (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.54 to 0.81, 12 RCTs, n = 1614, I(2) = 3%, moderate-quality evidence). This suggests that if 19% of women are aware of prolapse after native tissue repair, between 10% and 15% will be aware of prolapse after permanent mesh repair.Rates of repeat surgery for prolapse were lower in the mesh group (RR 0.53, 95% CI 0.31 to 0.88, 12 RCTs, n = 1675, I(2) = 0%, moderate-quality evidence). There was no evidence of a difference between the groups in rates of repeat surgery for continence (RR 1.07, 95% CI 0.62 to 1.83, 9 RCTs, n = 1284, I(2) = 21%, low quality evidence). More women in the mesh group required repeat surgery for the combined outcome of prolapse, stress incontinence, or mesh exposure (RR 2.40, 95% CI 1.51 to 3.81, 7 RCTs, n = 867, I(2) = 0%, moderate-quality evidence). This suggests that if 5% of women require repeat surgery after native tissue repair, between 7% and 18% in the permanent mesh group will do so. Eight per cent of women in the mesh group required repeat surgery for mesh exposure.Recurrent prolapse on examination was less likely after mesh repair (RR 0.40, 95% CI 0.30 to 0.53, 21 RCTs, n = 2494, I(2) = 73%, low-quality evidence). This suggests that if 38% of women have recurrent prolapse after native tissue repair, between 11% and 20% will do so after mesh repair.Permanent mesh was associated with higher rates of de novo stress incontinence (RR 1.39, 95% CI 1.06 to 1.82, 12 RCTs, 1512 women, I(2) = 0%, low-quality evidence) and bladder injury (RR 3.92, 95% CI 1.62 to 9.50, 11 RCTs, n = 1514, I(2) = 0%, moderate-quality evidence). There was no evidence of a difference between the groups in rates of de novo dyspareunia (RR 0.92, 95% CI 0.58 to 1.47, 11 RCTs, n = 764, I(2) = 21%, low-quality evidence). Effects on quality of life were uncertain due to the very low-quality evidence. Absorbable mesh versus native tissue repairThere was very low-quality evidence for the effectiveness of either form of repair at two years on the rate of awareness of prolapse (RR 1.05, 95% CI 0.77 to 1.44, 1 RCT, n = 54).There was very low-quality evidence for the effectiveness of either form of repair on the rate of repeat surgery for prolapse (RR 0.47, 95% CI 0.09 to 2.40, 1 RCT, n = 66).Recurrent prolapse on examination was less likely in the mesh group (RR 0.71, 95% CI 0.52 to 0.96, 3 RCTs, n = 292, I(2) = 21%, low-quality evidence)The effect of either form of repair was uncertain for urinary outcomes, dyspareunia, and quality of life. Biological graft versus native tissue repairThere was no evidence of a difference between the groups at one to three years for the outcome awareness of prolapse (RR 0.97, 95% CI 0.65 to 1.43, 7 RCTs, n = 777, low-quality evidence).There was no evidence of a difference between the groups for the outcome repeat surgery for prolapse (RR 1.22, 95% CI 0.61 to 2.44, 5 RCTs, n = 306, I(2) = 8%, low-quality evidence).The effect of either approach was very uncertain for recurrent prolapse (RR 0.94, 95% CI 0.60 to 1.47, 7 RCTs, n = 587, I(2) = 59%, very low-quality evidence).There was no evidence of a difference between the groups for dyspareunia or quality of life outcomes (very low-quality evidence). AUTHORS' CONCLUSIONS: While transvaginal permanent mesh is associated with lower rates of awareness of prolapse, reoperation for prolapse, and prolapse on examination than native tissue repair, it is also associated with higher rates of reoperation for prolapse, stress urinary incontinence, or mesh exposure and higher rates of bladder injury at surgery and de novo stress urinary incontinence. The risk-benefit profile means that transvaginal mesh has limited utility in primary surgery. While it is possible that in women with higher risk of recurrence the benefits may outweigh the risks, there is currently no evidence to support this position.Limited evidence suggests that absorbable mesh may reduce rates of recurrent prolapse on examination compared to native tissue repair, but there was insufficient evidence on absorbable mesh for us to draw any conclusions for other outcomes. There was also insufficient evidence for us to draw any conclusions regarding biological grafts compared to native tissue repair.In 2011, many transvaginal permanent meshes were voluntarily withdrawn from the market, and the newer, lightweight transvaginal permanent meshes still available have not been evaluated within a RCT. In the meantime, these newer transvaginal meshes should be utilised under the discretion of the ethics committee. PMID- 26858091 TI - Where are they now? Psychosocial, educational, and vocational outcomes after epilepsy surgery in childhood. AB - OBJECTIVE: To evaluate the social, educational, and vocational outcomes of young adults who underwent resective epilepsy surgery in childhood (4-11 years earlier), and in a comparison group of nonsurgical patients with intractable epilepsy. METHODS: Participants were 78 patients (mean age 22.37, standard deviation [SD] 2.47 years) with childhood onset intractable epilepsy, of whom 51 underwent surgery. At follow-up, participants were at least 18 years of age. Patients' current education, employment, income, and various social factors, including living arrangements, relationship status, and involvement with friends and community organizations were recorded. In addition, parents of patients completed the Adult Behaviour Checklist (ABCL). Employment status, education, and income were compared with provincial census data. RESULTS: There was no statistically significant difference in the proportion of surgical and nonsurgical patients who were seizure-free in the 12 months preceding the study: 53% and 33%, respectively (p = 0.10). Among all patients, 60% were enrolled in, or had completed, postsecondary education and 82% were employed or a student; similar to the general population. However, compared with population data, fewer patients with epilepsy (20%) had an annual income of $10,000 or greater (p < 0.001). Compared to normative data, a greater proportion of patients scored in the abnormal range in some ABCL scales (p < 0.028). Patients with IQs > 85 had significantly better educational, vocational, and psychosocial outcomes compared to patients with IQs <= 85. Surgical and nonsurgical patients did not differ on any outcome variable. Compared to patients with seizures, more seizure-free patients were living independently (p = 0.03), and had a driver's licence (p < 0.001). Other outcomes were similar among patients with and without seizures. SIGNIFICANCE: Overall, patients with intractable epilepsy in childhood attained educational and vocational outcomes similar to that of the general population, but earned a significantly lower income. Seizure freedom, attained through surgery or medication management, was associated with better outcomes in limited psychosocial measures. PMID- 26858089 TI - Plumericin inhibits proliferation of vascular smooth muscle cells by blocking STAT3 signaling via S-glutathionylation. AB - The etiology of atherosclerosis and restenosis involves aberrant inflammation and proliferation, rendering compounds with both anti-inflammatory and anti-mitogenic properties as promising candidates for combatting vascular diseases. A recent study identified the iridoid plumericin as a new scaffold inhibitor of the pro inflammatory NF-kappaB pathway in endothelial cells. We here examined the impact of plumericin on the proliferation of primary vascular smooth muscle cells (VSMC). Plumericin inhibited serum-stimulated proliferation of rat VSMC. It arrested VSMC in the G1/G0-phase of the cell cycle accompanied by abrogated cyclin D1 expression and hindered Ser 807/811-phosphorylation of retinoblastoma protein. Transient depletion of glutathione by the electrophilic plumericin led to S-glutathionylation as well as hampered Tyr705-phosphorylation and activation of the transcription factor signal transducer and activator of transcription 3 (Stat3). Exogenous addition of glutathione markedly prevented this inhibitory effect of plumericin on Stat3. It also overcame downregulation of cyclin D1 expression and the reduction of biomass increase upon serum exposure. This study revealed an anti-proliferative property of plumericin towards VSMC which depends on plumericin's thiol reactivity and S-glutathionylation of Stat3. Hence, plumericin, by targeting at least two culprits of vascular dysfunction inflammation and smooth muscle cell proliferation -might become a promising electrophilic lead compound for vascular disease therapy. PMID- 26858092 TI - Prewarming neurosurgical patients to minimize hypotension on induction of anesthesia: a randomized trial. AB - PURPOSE: Prewarming prior to surgery is effective in preventing perioperative hypothermia. There is a paucity of evidence, however, regarding the hemodynamic effects of prewarming. We hypothesized that the nadir mean arterial pressure during anesthesia induction would be higher after prewarming than after no prewarming. METHODS: We randomized 32 patients prior to elective neurosurgery to receive either one hour of forced-air convective warming at 46 degrees C or routine care (full body blanket with convective warmer attached but not turned on). All patients had invasive blood pressure, heart rate, and core temperature monitoring before and during warming and underwent a protocolized intravenous anesthetic induction with propofol and remifentanil target-controlled infusions. The primary endpoint was the nadir mean arterial blood pressure (MAP) during induction. Hypotension was defined as systolic blood pressure (SBP) < 90 mmHg, MAP < 60 mmHg, or a reduction in either SBP or MAP > 20% from baseline values. RESULTS: No difference was found in the mean (SD) nadir MAP between the prewarmed group and the control group [64 (11) mmHg vs 68 (16) mmHg, respectively; mean difference, 5 mmHg; 95% confidence interval (CI), -6 to 15; P = 0.36]. Similarly, there was no difference between groups in the incidence of hypotension (100% of prewarmed vs 93% of control patients; relative risk, 1.07; 95% CI, 0.94 to 1.23; P = 0.32) or in the requirement for vasopressors during induction (four patients in each group required metaraminol; P = 1.00). CONCLUSION: Prewarming with convective forced air for one hour prior to intravenous anesthetic induction did not prevent hypotension during the induction period (Australian New Zealand Clinical Trials Registry [ANZCTR] ACTRN12615000431527). PMID- 26858093 TI - Interleukin-1beta gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study. AB - BACKGROUND: We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. METHODS: All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as > 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes- was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. RESULTS: After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03 0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1beta (IL1beta), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). CONCLUSION: The results suggest a contribution of IL1beta in modulating susceptibility to postoperative QTc prolongation after cardiac surgery. PMID- 26858094 TI - Regulatory network of proton motive force: contribution of cyclic electron transport around photosystem I. AB - Cyclic electron transport around photosystem I (PSI) generates ?pH across the thylakoid membrane without net production of NADPH. In angiosperms, two pathways of PSI cyclic electron transport operate. The main pathway depends on PGR5/PGRL1 proteins and is likely identical to the historical Arnon's pathway. The minor pathway depends on chloroplast NADH dehydrogenase-like (NDH) complex. In assays of their rates in vivo, the two independent pathways are often mixed together. Theoretically, linear electron transport from water to NADP(+) cannot satisfy the ATP/NADPH production ratio required by the Calvin-Benson cycle and photorespiration. PGR5/PGRL1-dependent PSI cyclic electron transport contributes substantially to the supply of ATP for CO2 fixation, as does linear electron transport. Also, the contribution of chloroplast NDH cannot be ignored, especially at low light intensity, although the extent of the contribution depends on the plant species. An increase in proton conductivity of ATP synthase may compensate ATP synthesis to some extent in the pgr5 mutant. Combined with the decreased rate of ?pH generation, however, this mechanism sacrifices homeostasis of the thylakoid lumen pH, seriously disturbing the pH-dependent regulation of photosynthetic electron transport, induction of qE, and downregulation of the cytochrome b 6 f complex. PGR5/PGRL1-dependent PSI cyclic electron transport produces sufficient proton motive force for ATP synthesis and the regulation of photosynthetic electron transport. PMID- 26858095 TI - What Works and What's Safe in Pediatric Emergency Procedural Sedation: An Overview of Reviews. AB - BACKGROUND: Sedation is increasingly used to facilitate procedures on children in emergency departments (EDs). This overview of systematic reviews (SRs) examines the safety and efficacy of sedative agents commonly used for procedural sedation in children in the ED or similar settings. METHODS: We followed standard SR methods: comprehensive search; dual study selection, quality assessment, data extraction. We included SRs of children (1 month to 18 years) where the indication for sedation was procedure-related and performed in the ED. RESULTS: Fourteen SRs were included (210 primary studies). The most data were available for propofol (six reviews/50,472 sedations) followed by ketamine (7/8,238), nitrous oxide (5/8,220), and midazolam (4/4,978). Inconsistent conclusions for propofol were reported across six reviews. Half concluded that propofol was sufficiently safe; three reviews noted a higher occurrence of adverse events, particularly respiratory depression (upper estimate 1.1%; 5.4% for hypotension requiring intervention). Efficacy of propofol was considered in four reviews and found adequate in three. Five reviews found ketamine to be efficacious and seven reviews showed it to be safe. All five reviews of nitrous oxide concluded it is safe (0.1% incidence of respiratory events); most found it effective in cooperative children. Four reviews of midazolam made varying recommendations. To be effective, midazolam should be combined with another agent that increases the risk of adverse events (upper estimate 9.1% for desaturation, 0.1% for hypotension requiring intervention). CONCLUSIONS: This comprehensive examination of an extensive body of literature shows consistent safety and efficacy for nitrous oxide and ketamine, with very rare significant adverse events for propofol. There was considerable heterogeneity in outcomes and reporting across studies and previous reviews. Standardized outcome sets and reporting should be encouraged to facilitate evidence-based recommendations for care. PMID- 26858096 TI - Simvastatin Effect on Calcium and Silicon Plasma Levels in Postmenopausal Women with Osteoarthritis. AB - Postmenopausal women more often suffered from knee osteoarthritis and its pathogenesis still remains unclear. Calcium and silicon are significant elements involved in bone and joint metabolism, especially in older people. Cardiovascular diseases are common worldwide and simvastatin is the most prescribed drug in such population of patients. The purpose of this study was to evaluate the effect of simvastatin administration on calcium and silicon concentration in the plasma of postmenopausal women with osteoarthritis. Sixty postmenopausal mild hypercholesterolemic women (mean age 61.4 years, range 54-68) were enrolled. Thirty patients received simvastatin (20 or 40 mg/day) for at least 1 year before being enrolled (simvastatin "+" group). Control group consists of remaining 30 women (simvastatin "-"group). Silicon and calcium concentrations were measured spectrophotometrically. Plasma simvastatin level was determined 3 h after the drug administration using HPLC-UV-Vis. Calcium but not silicon level was significantly lower in patients receiving simvastatin in comparison with non statin group (1.91 +/- 0.32 vs. 2.33 +/- 0.19 mmol/l, p < 0.05). A weak but significant positive correlation between plasma silicon and simvastatin levels (r = 0.3, p < 0.05) was observed; this may be due to the fact that simvastatin contains silicon dioxide as an inactive ingredient. The mean simvastatin concentration was 9.02 ng/ml. All hypotheses were verified at the significance level of p < 0.05. A statistically significant decrease in the plasma calcium concentration of postmenopausal women, treated with simvastatin suggests that simvastatin may play a role in calcium metabolism in postmenopausal women with osteoarthritis. Positive correlation of simvastatin concentration with silicon level in the plasma suggests that both might prompt the positive effect of osteoarthritis treatment. PMID- 26858097 TI - Screening for Depression in Children and Adolescents: U.S. Preventive Services Task Force Recommendation Statement. AB - DESCRIPTION: Update of the 2009 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for major depressive disorder (MDD) in children and adolescents. METHODS: The USPSTF reviewed the evidence on the benefits and harms of screening; the accuracy of primary care-feasible screening tests; and the benefits and harms of treatment with psychotherapy, medications, and collaborative care models in patients aged 7 to 18 years. POPULATION: This recommendation applies to children and adolescents aged 18 years or younger who do not have a diagnosis of MDD. RECOMMENDATION: The USPSTF recommends screening for MDD in adolescents aged 12 to 18 years. Screening should be implemented with adequate systems in place to ensure accurate diagnosis, effective treatment, and appropriate follow-up. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for MDD in children aged 11 years or younger. (I statement). PMID- 26858098 TI - Author response to Dr Wise's letter. PMID- 26858099 TI - Expected number of asbestos-related lung cancers in the Netherlands in the next two decades: a comparison of methods. AB - OBJECTIVES: Exposure to asbestos fibres increases the risk of mesothelioma and lung cancer. Although the vast majority of mesothelioma cases are caused by asbestos exposure, the number of asbestos-related lung cancers is less clear. This number cannot be determined directly as lung cancer causes are not clinically distinguishable but may be estimated using varying modelling methods. METHODS: We applied three different modelling methods to the Dutch population supplemented with uncertainty ranges (UR) due to uncertainty in model input values. The first method estimated asbestos-related lung cancer cases directly from observed and predicted mesothelioma cases in an age-period-cohort analysis. The second method used evidence on the fraction of lung cancer cases attributable (population attributable risk (PAR)) to asbestos exposure. The third method incorporated risk estimates and population exposure estimates to perform a life table analysis. RESULTS: The three methods varied substantially in incorporated evidence. Moreover, the estimated number of asbestos-related lung cancer cases in the Netherlands between 2011 and 2030 depended crucially on the actual method applied, as the mesothelioma method predicts 17 500 expected cases (UR 7000-57 000), the PAR method predicts 12 150 cases (UR 6700-19 000), and the life table analysis predicts 6800 cases (UR 6800-33 850). CONCLUSIONS: The three different methods described resulted in absolute estimates varying by a factor of ~2.5. These results show that accurate estimation of the impact of asbestos exposure on the lung cancer burden remains a challenge. PMID- 26858100 TI - Distinct Contributions of Enzymic Functional Groups to the 2',3'-Cyclic Phosphodiesterase, 3'-Phosphate Guanylylation, and 3'-ppG/5'-OH Ligation Steps of the Escherichia coli RtcB Nucleic Acid Splicing Pathway. AB - Escherichia coli RtcB is a founding member of a family of manganese-dependent RNA repair enzymes that join RNA 2',3'-cyclic phosphate (RNA>p) or RNA 3'-phosphate (RNAp) ends to 5'-OH RNA (HORNA) ends in a multistep pathway whereby RtcB (i) hydrolyzes RNA>p to RNAp, (ii) transfers GMP from GTP to RNAp to form to RNAppG, and (iii) directs the attack of 5'-OH on RNAppG to form a 3'-5' phosphodiester splice junction. The crystal structure of the homologous archaeal RtcB enzyme revealed an active site with two closely spaced manganese ions, Mn1 and Mn2, that interact with the GTP phosphates. By studying the reactions of wild-type E. coli RtcB and RtcB alanine mutants with 3'-phosphate-, 2',3'-cyclic phosphate-, and 3' ppG-terminated substrates, we found that enzymic constituents of the two metal coordination complexes (Cys78, His185, and His281 for Mn1 and Asp75, Cys78, and His168 for Mn2 in E. coli RtcB) play distinct catalytic roles. For example, whereas the C78A mutation abolished all steps assayed, the D75A mutation allowed cyclic phosphodiester hydrolysis but crippled 3'-phosphate guanylylation, and the H281A mutant was impaired in overall HORNAp and HORNA>p ligation but was able to seal a preguanylylated substrate. The archaeal counterpart of E. coli RtcB Arg189 coordinates a sulfate anion construed to mimic the position of an RNA phosphate. We propose that Arg189 coordinates a phosphodiester at the 5'-OH end, based on our findings that the R189A mutation slowed the step of RNAppG/HORNA sealing by a factor of 200 compared to that with wild-type RtcB while decreasing the rate of RNAppG formation by only 3-fold. IMPORTANCE: RtcB enzymes comprise a widely distributed family of manganese- and GTP-dependent RNA repair enzymes that ligate 2',3'-cyclic phosphate ends to 5'-OH ends via RNA 3'-phosphate and RNA(3')pp(5')G intermediates. The RtcB active site includes two adjacent manganese ions that engage the GTP phosphates. Alanine scanning of Escherichia coli RtcB reveals distinct contributions of metal-binding residues Cys78, Asp75, and His281 at different steps of the RtcB pathway. The RNA contacts of RtcB are uncharted. Mutagenesis implicates Arg189 in engaging the 5'-OH RNA end. PMID- 26858101 TI - WrpA Is an Atypical Flavodoxin Family Protein under Regulatory Control of the Brucella abortus General Stress Response System. AB - The general stress response (GSR) system of the intracellular pathogen Brucella abortus controls the transcription of approximately 100 genes in response to a range of stress cues. The core genetic regulatory components of the GSR are required for B. abortus survival under nonoptimal growth conditions in vitro and for maintenance of chronic infection in an in vivo mouse model. The functions of the majority of the genes in the GSR transcriptional regulon remain undefined. bab1_1070 is among the most highly regulated genes in this regulon: its transcription is activated 20- to 30-fold by the GSR system under oxidative conditions in vitro. We have solved crystal structures of Bab1_1070 and demonstrate that it forms a homotetrameric complex that resembles those of WrbA type NADH:quinone oxidoreductases, which are members of the flavodoxin protein family. However, B. abortus WrbA-related protein (WrpA) does not bind flavin cofactors with a high affinity and does not function as an NADH:quinone oxidoreductase in vitro. Soaking crystals with flavin mononucleotide (FMN) revealed a likely low-affinity binding site adjacent to the canonical WrbA flavin binding site. Deletion of wrpA (DeltawrpA) does not compromise cell survival under acute oxidative stress in vitro or attenuate infection in cell-based or mouse models. However, a DeltawrpA strain does elicit increased splenomegaly in a mouse model, suggesting that WrpA modulates B. abortus interaction with its mammalian host. Despite high structural homology with canonical WrbA proteins, we propose that B. abortus WrpA represents a functionally distinct member of the diverse flavodoxin family. IMPORTANCE: Brucella abortus is an etiological agent of brucellosis, which is among the most common zoonotic diseases worldwide. The general stress response (GSR) regulatory system of B. abortus controls the transcription of approximately 100 genes and is required for maintenance of chronic infection in a murine model; the majority of GSR-regulated genes remain uncharacterized. We present in vitro and in vivo functional and structural analyses of WrpA, whose expression is strongly induced by GSR under oxidative conditions. Though WrpA is structurally related to NADH:quinone oxidoreductases, it does not bind redox cofactors in solution, nor does it exhibit oxidoreductase activity in vitro. However, WrpA does affect spleen inflammation in a murine infection model. Our data provide evidence that WrpA forms a new functional class of WrbA/flavodoxin family proteins. PMID- 26858104 TI - XoxF Acts as the Predominant Methanol Dehydrogenase in the Type I Methanotroph Methylomicrobium buryatense. AB - Many methylotrophic taxa harbor two distinct methanol dehydrogenase (MDH) systems for oxidizing methanol to formaldehyde: the well-studied calcium-dependent MxaFI type and the more recently discovered lanthanide-containing XoxF type. MxaFI has traditionally been accepted as the major functional MDH in bacteria that contain both enzymes. However, in this study, we present evidence that, in a type I methanotroph, Methylomicrobium buryatense, XoxF is likely the primary functional MDH in the environment. The addition of lanthanides increases xoxF expression and greatly reduces mxa expression, even under conditions in which calcium concentrations are almost 100-fold higher than lanthanide concentrations. Mutations in genes encoding the MDH enzymes validate our finding that XoxF is the major functional MDH, as XoxF mutants grow more poorly than MxaFI mutants under unfavorable culturing conditions. In addition, mutant and transcriptional analyses demonstrate that the lanthanide-dependent MDH switch operating in methanotrophs is mediated in part by the orphan response regulator MxaB, whose gene transcription is itself lanthanide responsive. IMPORTANCE: Aerobic methanotrophs, bacteria that oxidize methane for carbon and energy, require a methanol dehydrogenase enzyme to convert methanol into formaldehyde. The calcium dependent enzyme MxaFI has been thought to primarily carry out methanol oxidation in methanotrophs. Recently, it was discovered that XoxF, a lanthanide-containing enzyme present in most methanotrophs, can also oxidize methanol. In a methanotroph with both MxaFI and XoxF, we demonstrate that lanthanides transcriptionally control genes encoding the two methanol dehydrogenases, in part by controlling expression of the response regulator MxaB. Lanthanides are abundant in the Earth's crust, and we demonstrate that micromolar amounts of lanthanides are sufficient to suppress MxaFI expression. Thus, we present evidence that XoxF acts as the predominant methanol dehydrogenase in a methanotroph. PMID- 26858105 TI - Fluorescence-Detected Linear Dichroism of Wood Cell Walls in Juvenile Serbian Spruce: Estimation of Compression Wood Severity. AB - Fluorescence-detected linear dichroism (FDLD) microscopy provides observation of structural order in a microscopic sample and its expression in numerical terms, enabling both quantitative and qualitative comparison among different samples. We applied FDLD microscopy to compare the distribution and alignment of cellulose fibrils in cell walls of compression wood (CW) and normal wood (NW) on stem cross sections of juvenile Picea omorika trees. Our data indicate a decrease in cellulose fibril order in CW compared with NW. Radial and tangential walls differ considerably in both NW and CW. In radial walls, cellulose fibril order shows a gradual decrease from NW to severe CW, in line with the increase in CW severity. This indicates that FDLD analysis of cellulose fibril order in radial cell walls is a valuable method for estimation of CW severity. PMID- 26858102 TI - Lack of the H-NS Protein Results in Extended and Aberrantly Positioned DNA during Chromosome Replication and Segregation in Escherichia coli. AB - The architectural protein H-NS binds nonspecifically to hundreds of sites throughout the chromosome and can multimerize to stiffen segments of DNA as well as to form DNA-protein-DNA bridges. H-NS has been suggested to contribute to the orderly folding of the Escherichia coli chromosome in the highly compacted nucleoid. In this study, we investigated the positioning and dynamics of the origins, the replisomes, and the SeqA structures trailing the replication forks in cells lacking the H-NS protein. In H-NS mutant cells, foci of SeqA, replisomes, and origins were irregularly positioned in the cell. Further analysis showed that the average distance between the SeqA structures and the replisome was increased by ~100 nm compared to that in wild-type cells, whereas the colocalization of SeqA-bound sister DNA behind replication forks was not affected. This result may suggest that H-NS contributes to the folding of DNA along adjacent segments. H-NS mutant cells were found to be incapable of adopting the distinct and condensed nucleoid structures characteristic of E. coli cells growing rapidly in rich medium. It appears as if H-NS mutant cells adopt a "slow growth" type of chromosome organization under nutrient-rich conditions, which leads to a decreased cellular DNA content. IMPORTANCE: It is not fully understood how and to what extent nucleoid-associated proteins contribute to chromosome folding and organization during replication and segregation in Escherichia coli. In this work, we find in vivo indications that cells lacking the nucleoid associated protein H-NS have a lower degree of DNA condensation than wild-type cells. Our work suggests that H-NS is involved in condensing the DNA along adjacent segments on the chromosome and is not likely to tether newly replicated strands of sister DNA. We also find indications that H-NS is required for rapid growth with high DNA content and for the formation of a highly condensed nucleoid structure under such conditions. PMID- 26858106 TI - NATpipe: an integrative pipeline for systematical discovery of natural antisense transcripts (NATs) and phase-distributed nat-siRNAs from de novo assembled transcriptomes. AB - Nat-siRNAs (small interfering RNAs originated from natural antisense transcripts) are a class of functional small RNA (sRNA) species discovered in both plants and animals. These siRNAs are highly enriched within the annealed regions of the NAT (natural antisense transcript) pairs. To date, great research efforts have been taken for systematical identification of the NATs in various organisms. However, developing a freely available and easy-to-use program for NAT prediction is strongly demanded by researchers. Here, we proposed an integrative pipeline named NATpipe for systematical discovery of NATs from de novo assembled transcriptomes. By utilizing sRNA sequencing data, the pipeline also allowed users to search for phase-distributed nat-siRNAs within the perfectly annealed regions of the NAT pairs. Additionally, more reliable nat-siRNA loci could be identified based on degradome sequencing data. A case study on the non-model plant Dendrobium officinale was performed to illustrate the utility of NATpipe. Finally, we hope that NATpipe would be a useful tool for NAT prediction, nat-siRNA discovery, and related functional studies. NATpipe is available at www.bioinfolab.cn/NATpipe/NATpipe.zip. PMID- 26858107 TI - A new test for plant bioaccessibility in sulphidic wastes and soils: A case study from the Wheal Maid historic tailings repository in Cornwall, UK. AB - Currently, bioaccessibility testing at contaminated sites is dominated by techniques designed to assess oral bioaccessibility to humans. Determining the plant bioaccessibility of toxic trace elements is also important. In mining landscapes, sulphides are an important source of potentially toxic elements. Simple tests to evaluate readily leachable metals and metalloids exist but do not extract elements temporarily constrained within the sulphide fraction. Sequential extractions describe the association of trace elements with different geochemical fractions but are time consuming, costly and provide excessive detail. This paper proposes a new test for plant bioaccessibility in sulphidic mine wastes and soils that uses hydrogen peroxide to simulate environmental oxidation. The bioaccessible fraction determined is operationally defined and does not predict actual plant uptake. The test targets a) the portion of an element that is currently available in the pore water for uptake by plant roots and also b) the fraction that is temporarily constrained in sulphide minerals but may become available upon oxidation of the substrate. A case study was conducted at a historic mine waste repository site in Cornwall, U.K. where near total As concentrations were extremely elevated and Cd, Cu, Pb, Sb and Zn were also high. Our test determined that bioaccessible concentrations of As, Cd, Cu and Zn and to a lesser extent Sb and Pb were highest in samples of pyritic grey tailings. This is attributed to sulphide mineral oxidation and, particularly for Cd and Zn, the dissolution of soluble secondary minerals. High As concentrations in the marbled tailings were not bioaccessible. Results from the case study show that this new test provides useful information on the future bioaccessibility of contaminants, allowing for classification of mineralised sulphidic waste materials which otherwise cannot be obtained using established geochemical and mineralogical techniques. Furthermore, the test is rapid, repeatable and cost effective. PMID- 26858103 TI - Molecular Characterization of the Vacuolating Autotransporter Toxin in Uropathogenic Escherichia coli. AB - The vacuolating autotransporter toxin (Vat) contributes to uropathogenic Escherichia coli (UPEC) fitness during systemic infection. Here, we characterized Vat and investigated its regulation in UPEC. We assessed the prevalence of vat in a collection of 45 UPEC urosepsis strains and showed that it was present in 31 (68%) of the isolates. The isolates containing the vat gene corresponded to three major E. coli sequence types (ST12, ST73, and ST95), and these strains secreted the Vat protein. Further analysis of the vat genomic locus identified a conserved gene located directly downstream of vat that encodes a putative MarR-like transcriptional regulator; we termed this gene vatX The vat-vatX genes were present in the UPEC reference strain CFT073, and reverse transcriptase PCR (RT PCR) revealed that the two genes are cotranscribed. Overexpression of vatX in CFT073 led to a 3-fold increase in vat gene transcription. The vat promoter region contained three putative nucleation sites for the global transcriptional regulator histone-like nucleoid structuring protein (H-NS); thus, the hns gene was mutated in CFT073 (to generate CFT073 hns). Western blot analysis using a Vat specific antibody revealed a significant increase in Vat expression in CFT073 hns compared to that in wild-type CFT073. Direct H-NS binding to the vat promoter region was demonstrated using purified H-NS in combination with electrophoresis mobility shift assays. Finally, Vat-specific antibodies were detected in plasma samples from urosepsis patients infected by vat-containing UPEC strains, demonstrating that Vat is expressed during infection. Overall, this study has demonstrated that Vat is a highly prevalent and tightly regulated immunogenic serine protease autotransporter protein of Enterobacteriaceae (SPATE) secreted by UPEC during infection. IMPORTANCE: Uropathogenic Escherichia coli (UPEC) is the major cause of hospital- and community-acquired urinary tract infections. The vacuolating autotransporter toxin (Vat) is a cytotoxin known to contribute to UPEC fitness during murine sepsis infection. In this study, Vat was found to be highly conserved and prevalent among a collection of urosepsis clinical isolates and was expressed at human core body temperature. Regulation of vat was demonstrated to be directly repressed by the global transcriptional regulator H NS and upregulated by the downstream gene vatX (encoding a new MarR-type transcriptional regulator). Additionally, increased Vat-specific IgG titers were detected in plasma from corresponding urosepsis patients infected with vat positive isolates. Hence, Vat is a highly conserved and tightly regulated urosepsis-associated virulence factor. PMID- 26858108 TI - Resistin gene polymorphisms are associated with acne and serum lipid levels, providing a potential nexus between lipid metabolism and inflammation. AB - Acne vu lgaris is a multifactorial inflammatory skin disease causing social stigma and psychological effect on patients. We hypothesized that the genes that can affect both lipid metabolism and inflammation may be central for acne formation and present targets for treatment. Pro-inflammatory adipokine resistin, one such likely target, activates NFkB and JNK pathways inducing TLR-2, IL-1, IL 6, and TNFalpha genes. The polymorphisms in promoter and intron region of the resistin gene affect its expression levels. Therefore, we explored the association of resistin polymorphisms (RETN +299G > A and -420C > G) with pathogenesis of acne vulgaris. We used PCR-RFLP method to genotype at the two single nucleotide polymorphisms at RETN promoter in 530 acne patients vs. 550 age and sex-matched control subjects. We also measured serum lipid levels in acne patients and associated these with RETN genotypes. We found that the RETN gene polymorphisms are strongly associated with acne vulgaris and the severity of acne symptoms. In females the variant allele frequencies of both SNPs are statistically higher in patients than in controls; in males frequency distribution does not reach significance. The haplotype containing both variant alleles is significantly more common in patients than in controls. We find no association of RETN SNPs with the acne types. Importantly, we found that the levels of HDL-C were significantly decreased in variant genotype of RETN. Our results show that the RETN polymorphisms expected to boost resistin expression increase the risk of developing acne. We suggest that resistin may provide an attractive target for treatment. PMID- 26858109 TI - The expression profile of filaggrin-2 in the normal and pathologic human oral mucosa. AB - The epithelial cells of the oral cavity show a remarkable degree of regional variation with respect to their morphology and keratinization status. In the oral cavity, the tongue and palate contain keratinizing stratified epithelia, while the buccal mucosa contains non-keratinizing stratified epithelia. We herein examined the expression of filaggrin-2, a member of the S100 fused-type protein family, in the oral mucosa. Filaggrin-2 was weakly expressed in the normal epithelium of the palate, but not in the buccal mucosa or tongue, although filaggrin protein was observed in the epithelium of the buccal mucosa and the palate. We next examined the expression of filaggrin-2 in the oral mucosa of subjects with hyperkeratotic diseases. The expression of filaggrin-2 was markedly increased in the epithelium of the oral mucosa in patients with lichen planus, leukokeratosis and leukoplakia. Filaggrin-2 positivity was observed in granules, some of which were co-localized with those of filaggrin. These results indicate that filaggrin-2 was expressed in the oral mucosa under certain pathological conditions, demonstrating that an aberrant protein expression, together with filaggrin, indicates the altered differentiation program including hyperkeratosis that occurs in these diseases. PMID- 26858110 TI - Does Size Matter? A Study of Risk Perceptions of Global Population Growth. AB - The global human population now exceeds 7 billion and is projected to reach 10 billion around 2060. While population growth has been associated with certain benefits (e.g., economies of scale, technological advancements), theoretical models, probabilistic projections, and empirical evidence also indicate that this growth could increase the likelihood of many adverse events (e.g., climate change, resource shortages) and the impact of these events, as more people are exposed to the outcomes. While concerns about these issues are well-documented in the academic literature, there is little evidence concerning the public's perceptions of the risks associated with global population growth (GPG) and how these perceptions are likely to influence related decisions. To address these issues, we conducted a U.K.-based study that examined respondents' risk perceptions of GPG, their willingness to embrace mitigation/precautionary behaviors, and reasons for variations in these two factors. We found that GPG is perceived as a moderate-to-high risk, with concerns about the increased likelihood of resource shortages, ecological damage, and violent conflict being foremost. Respondents believed that the worst effects of GPG would arrive around 2050 and would be experienced by the world's poorest people. Respondents who perceived greater levels of risk from GPG were generally those who indicated a greater willingness to embrace mitigation behaviors (e.g., reduce resource consumption) and preventative actions (e.g., support political action to limit growth). We discuss how our findings might be utilized to better manage the potential challenges associated with GPG and we suggest several directions for further research. PMID- 26858111 TI - Convergence in Multispecies Interactions. AB - The concepts of convergent evolution and community convergence highlight how selective pressures can shape unrelated organisms or communities in similar ways. We propose a related concept, convergent interactions, to describe the independent evolution of multispecies interactions with similar physiological or ecological functions. A focus on convergent interactions clarifies how natural selection repeatedly favors particular kinds of associations among species. Characterizing convergent interactions in a comparative context is likely to facilitate prediction of the ecological roles of organisms (including microbes) in multispecies interactions and selective pressures acting in poorly understood or newly discovered multispecies systems. We illustrate the concept of convergent interactions with examples: vertebrates and their gut bacteria; ectomycorrhizae; insect-fungal-bacterial interactions; pitcher-plant food webs; and ants and ant plants. PMID- 26858112 TI - cloncase: Estimation of sex frequency and effective population size by clonemate resampling in partially clonal organisms. AB - Inferring reproductive and demographic parameters of populations is crucial to our understanding of species ecology and evolutionary potential but can be challenging, especially in partially clonal organisms. Here, we describe a new and accurate method, cloncase, for estimating both the rate of sexual vs. asexual reproduction and the effective population size, based on the frequency of clonemate resampling across generations. Simulations showed that our method provides reliable estimates of sex frequency and effective population size for a wide range of parameters. The cloncase method was applied to Puccinia striiformis f.sp. tritici, a fungal pathogen causing stripe/yellow rust, an important wheat disease. This fungus is highly clonal in Europe but has been suggested to recombine in Asia. Using two temporally spaced samples of P. striiformis f.sp. tritici in China, the estimated sex frequency was 75% (i.e. three-quarter of individuals being sexually derived during the yearly sexual cycle), indicating strong contribution of sexual reproduction to the life cycle of the pathogen in this area. The inferred effective population size of this partially clonal organism (Nc = 998) was in good agreement with estimates obtained using methods based on temporal variations in allelic frequencies. The cloncase estimator presented herein is the first method allowing accurate inference of both sex frequency and effective population size from population data without knowledge of recombination or mutation rates. cloncase can be applied to population genetic data from any organism with cyclical parthenogenesis and should in particular be very useful for improving our understanding of pest and microbial population biology. PMID- 26858113 TI - Larger voids in mechanically stable, loose packings of 1.3MUm frictional, cohesive particles: Their reconstruction, statistical analysis, and impact on separation efficiency. AB - Lateral transcolumn heterogeneities and the presence of larger voids in a packing (comparable to the particle size) can limit the preparation of efficient chromatographic columns. Optimizing and understanding the packing process provides keys to better packing structures and column performance. Here, we investigate the slurry-packing process for a set of capillary columns packed with C18-modified, 1.3MUm bridged-ethyl hybrid porous silica particles. The slurry concentration used for packing 75MUm i.d. fused-silica capillaries was increased gradually from 5 to 50mg/mL. An intermediate concentration (20mg/mL) resulted in the best separation efficiency. Three capillaries from the set representing low, intermediate, and high slurry concentrations were further used for three dimensional bed reconstruction by confocal laser scanning microscopy and morphological analysis of the bed structure. Previous studies suggest increased slurry concentrations will result in higher column efficiency due to the suppression of transcolumn bed heterogeneities, but only up to a critical concentration. Too concentrated slurries favour the formation of larger packing voids (reaching the size of the average particle diameter). Especially large voids, which can accommodate particles from>90% of the particle size distribution, are responsible for a decrease in column efficiency at high slurry concentrations. Our work illuminates the increasing difficulty of achieving high bed densities with small, frictional, cohesive particles. As particle size decreases interparticle forces become increasingly important and hinder the ease of particle sliding during column packing. While an optimal slurry concentration is identified with respect to bed morphology and separation efficiency under conditions in this work, our results suggest adjustments of this concentration are required with regard to particle size, surface roughness, column dimensions, slurry liquid, and external effects utilized during the packing process (pressure protocol, ultrasound, electric fields). PMID- 26858114 TI - Determination of Alternaria mycotoxins in wine and juice using ionic liquid modified countercurrent chromatography as a pretreatment method followed by high performance liquid chromatography. AB - Alternariol (AOH), alternariol monomethyl ether (AME), and tenuazonic acid (TeA) are some of the main Alternaria mycotoxins that can be found as contaminants in food materials. The objective of this study was to develop a pretreatment method with countercurrent chromatography (CCC) for enrichment and cleanup of trace Alternaria mycotoxins in food samples prior to high-performance liquid chromatography (HPLC) analysis. An Analytical CCC instrument with a column volume 22.5mL was used, and a two-phase solvent system composed of ethyl acetate and water modified with 6% [HOOMIM][Cl] in mass to volume ratio was selected. Under the optimized CCC operation conditions, trace amounts of AOH, AME, and TeA in large volume of liquid sample were efficiently extracted and enriched in the stationary phase, and then eluted out just by reversing the stationary phase as mobile phase in the opposite flowing direction tail-to-head. The enrichment and elution strategies are unique and can be fulfilled online with high enrichment factors (87-114) and high recoveries (81.14-110.94%). The method has been successively applied to the determination of Alternaria mycotoxins in real apple juice and wine samples with the limits of detection (LOD) in the range of 0.03 0.14MUgL(-1). Totally 12 wine samples and 15 apple juice samples from the local market were analyzed. The detection rate of AOH and AME in both kinds of the samples were more than 50%, while TeA was found in relatively high level of 1.75 49.61MUgL(-1) in some of the apple juice samples. The proposed method is simple, rapid, and sensitive and could also be used for the analysis and monitoring of Alternaria mycotoxin in other food samples. PMID- 26858115 TI - Separation of small organic molecules using covalent organic frameworks-LZU1 as stationary phase by open-tubular capillary electrochromatography. AB - Covalent organic frameworks (COFs) have attracted much attention because of their permanent nanoscale porosity and higher surface area compared to zeolites as well as robustness. COFs have great potential in several fields such as hydrogen storage, gas separation, and catalysis. However, COFs have not yet been applied in capillary electrochromatography. Herein, covalent organic frameworks-LZU1 (COF LZU1) was used as the stationary phase in open-tubular capillary electrochromatography for the first time. Compared to the monoliths used in electrochromatography, the preparation technique of a COF-LZU1-coated capillary was simple and practical. The baseline separation of model analytes including alkylbenzenes, polyaromatic hydrocarbons, and anilines by the COF-LZU1-coated capillary was achieved based on the size selectivity of COF-LZU1 porous structure and hydrophobic interactions between the model analytes and organic ligands of COF-LZU1. The load capacity of the COF-LZU1-coated capillary for naphthalene was 0.6mg/mL. For three consecutive runs, the intraday relative standard deviations (RSDs) were 1.4-2.6% for the migration time and 2.7-8.7% for the peak area. The interday RSDs were 1.3-3.9% for the migration time and 3.7-9.7% for the peak area. The column-to-column reproducibility of migration time was in the range 1.0 3.9%. Moreover, the coated capillary was used for >300 runs with no changes in the separation efficiency. Thus, COFs have great potential in capillary electrochromatography and may provide a new method for chromatographic separation. PMID- 26858117 TI - Determination of androgens and progestogens in environmental and biological samples using fabric phase sorptive extraction coupled to ultra-high performance liquid chromatography tandem mass spectrometry. AB - Androgens and progestogens are two important groups of endocrine disrupting compounds (EDCs) which are implicated to produce severe detrimental impact over aquatic biota, even at very low concentrations of ngL(-1). For this reason, one of the major challenges to analytical chemists is the development of sensitive and selective extraction processes which allow the rapid and green determination of these emerging pollutants at low concentrations in environmental samples. Fabric phase sorptive extraction is a new, highly sensitive, efficient and solvent minimized technique which combine the advantages of sol-gel derived microextraction sorbents and the rich surface chemistry of cellulose fabric substrate. This process has several advantages such as minimum usage of organic solvents, short extraction times, small sample volumes and high analyte preconcentration factors. In this study, an extraction method based on sorptive fabric phase coupled to ultra-high-performance liquid chromatography tandem mass spectrometry detection (FPSE-UHPLC-MS/MS) has been developed for the determination of four progestogens and six androgens in environmental and biological samples. All the parameters involved in the extraction, such as sample volume, extraction and desorption times, desorption solvent volume and sample pH values have been optimized. The developed method provides satisfactory limits of detection (between 1.7 and 264ngL(-1)), good recoveries and low relative standard deviations (below 10% in tap and osmosis water and below 20% in wastewater and urine). Subsequently, the method was used to analyse tap water, wastewater treated with different processing technologies and urine samples. The concentrations of the detected hormones ranged from 28.3 to 227.3 ngL(-1) in water samples and from 1.1 to 3.7MUgL(-1) in urine samples. PMID- 26858116 TI - 1-Butyl-3-aminopropyl imidazolium-functionalized graphene oxide as a nanoadsorbent for the simultaneous extraction of steroids and beta-blockers via dispersive solid-phase microextraction. AB - In this study, we describe the synthesis of graphene oxide functionalized with the ionic liquid 1-butyl-3-aminopropyl imidazolium chloride and its use as an adsorbent for the dispersive solid-phase microextraction (micro SPE) of four anabolic steroids and six beta-blockers from aqueous samples of environmental importance, prior to their HPLC-diode array detector analysis. As the ionic liquid is covalently attached to graphene oxide sheets, it is made possible for it to participate in the dispersive micro SPE procedure. The limits of detection and limits of quantification of the proposed method were found to be in the range of 7-23ng/L and between 20 and 70ng/L, respectively. The linearity was satisfactory, with the determination coefficients to range from 0.9940 to 0.9998 while the within- and between-day relative standard deviation of the method ranged between 3.1 and 7.6% and from 4.0 to 8.5%, respectively. In order to test the applicability of the proposed method in real-life samples, the effluent from a municipal wastewater treatment plant as well as natural water samples from two rivers and a lake were collected and analyzed. After the analysis of samples, the effluent from municipal wastewater treatment plant was fortified with the analytes, at concentrations equal to 2 and 10 times the LOQs. Recoveries were calculated after subtracting the native (no-spike) concentrations of analytes, when needed. All the recoveries were in the range of 87-98%. A comparison study attests to the superiority of the developed nanomaterial over graphene oxide and graphene for the dispersive micro SPE of steroids and beta-blockers. PMID- 26858118 TI - Hydrophilic interaction liquid chromatography-mass spectrometry of (lyso)phosphatidic acids, (lyso)phosphatidylserines and other lipid classes. AB - The goal of this work is a systematic optimization of hydrophilic interaction liquid chromatography (HILIC) separation of acidic lipid classes (namely phosphatidic acids-PA, lysophosphatidic acids-LPA, phosphatidylserines-PS and lysophosphatidylserines-LPS) and other lipid classes under mass spectrometry (MS) compatible conditions. The main parameters included in this optimization are the type of stationary phases used in HILIC, pH of the mobile phase, the type and concentration of mobile phase additives. Nine HILIC columns with different chemistries (unmodified silica, modified silica using diol, 2-picolylamine, diethylamine and 1-aminoanthracene and hydride silica) are compared with the emphasis on peak shapes of acidic lipid classes. The optimization of pH is correlated with the theoretical calculation of acidobasic equilibria of studied lipid classes. The final method using the hydride column, pH 4 adjusted by formic acid and the gradient of acetonitrile and 40 mmol/L of aqueous ammonium formate provides good peak shapes for all analyzed lipid classes including acidic lipids. This method is applied for the identification of lipids in real samples of porcine brain and kidney extracts. PMID- 26858119 TI - The Plasmodium falciparum chloroquine resistance transporter is associated with the ex vivo P. falciparum African parasite response to pyronaridine. AB - BACKGROUND: The pyronaridine-artesunate combination is one of the most recent oral artemisinin-based therapeutic combinations (ACTs) recommended for the treatment of uncomplicated P. falciparum malaria. The emergence of P. falciparum resistance to artemisinin has recently developed in Southeast Asia. Little data are available on the association between pyronaridine susceptibility and polymorphisms in genes involved in antimalarial drug resistance. The objective of the present study was to investigate the association between ex vivo responses to pyronaridine and the K76T mutation in the pfcrt gene in P. falciparum isolates. METHODS: The assessment of ex vivo susceptibility to pyronaridine was performed on 296 P. falciparum isolates using a standard 42-h 3H-hypoxanthine uptake inhibition method. The K76T mutation was also investigated. RESULTS: The pyronaridine IC50 (inhibitory concentration 50 %) ranged from 0.55 to 80.0 nM. Ex vivo responses to pyronaridine were significantly associated with the K76T mutation (p-value = 0.020). The reduced susceptibility to pyronaridine, defined as IC50 > 60 nM, was significantly associated with the K76T mutation (p-value = 0.004). Using a Bayesian mixture modelling approach, the pyronaridine IC50 were classified into three components: component A (IC50 median 15.9 nM), component B (IC50 median 34.2 nM) and component C (IC50 median 63.3 nM). The K76T mutation was represented in 46.3% of the isolates in component A, 47.2% of the isolates in component B and 73.3% of the isolates in component C (p-value = 0.021). CONCLUSION: These results showed the ex vivo reduced susceptibility to pyronaridine, i.e., IC50 > 60 nM, associated with the K76T mutation. PMID- 26858120 TI - Genetic diversity among Plasmodium vivax isolates along the Thai-Myanmar border of Thailand. AB - BACKGROUND: Knowledge of the population genetics and transmission dynamics of Plasmodium vivax is crucial in predicting the emergence of drug resistance, relapse pattern and novel parasite phenotypes, all of which are relevant to the control of vivax infections. The aim of this study was to analyse changes in the genetic diversity of P. vivax genes from field isolates collected at different times along the Thai-Myanmar border. METHODS: Two hundred and fifty-four P. vivax isolates collected during two periods 10 years apart along the Thai-Myanmar border were analysed. The parasites were genotyped by nested-PCR and PCR-RFLP targeting selected polymorphic loci of Pvmsp1, Pvmsp3alpha and Pvcsp genes. RESULTS: The total number of distinguishable allelic variants observed for Pvcsp, Pvmsp1, and Pvmsp3alpha was 17, 7 and 3, respectively. High genetic diversity was observed for Pvcsp (H E = 0.846) and Pvmsp1 (H E = 0.709). Of the 254 isolates, 4.3 and 14.6 % harboured mixed Pvmsp1 and Pvcsp genotypes with a mean multiplicity of infection (MOI) of 1.06 and 1.15, respectively. The overall frequency of multiple genotypes was 16.9 %. When the frequencies of allelic variants of each gene during the two distinct periods were analysed, significant differences were noted for Pvmsp1 (P = 0.018) and the Pvcsp (P = 0.033) allelic variants. CONCLUSION: Despite the low malaria transmission levels in Thailand, P. vivax population exhibit a relatively high degree of genetic diversity along the Thai-Myanmar border of Thailand, in particular for Pvmsp1 and Pvcsp, with indication of geographic and temporal variation in frequencies for some variants. These results are of relevance to monitoring the emergence of drug resistance and to the elaboration of measures to control vivax malaria. PMID- 26858123 TI - The race for combined checkpoint inhibition in NSCLC. PMID- 26858121 TI - Metformin promotes tau aggregation and exacerbates abnormal behavior in a mouse model of tauopathy. AB - BACKGROUND: Alzheimer disease (AD) and other tauopathies develop cerebral intracellular inclusions of hyperphosphorylated tau. Epidemiological and experimental evidence suggests a clear link between type 2 diabetes mellitus and AD. In AD animal models, tau pathology is exacerbated by metabolic comorbidities, such as insulin resistance and diabetes. Within this context, anitidiabetic drugs, including the widely-prescribed insulin-sensitizing drug metformin, are currently being investigated for AD therapy. However, their efficacy for tauopathy in vivo has not been tested. RESULTS: Here, we report that in the P301S mutant human tau (P301S) transgenic mouse model of tauopathy, chronic administration of metformin exerts paradoxical effects on tau pathology. Despite reducing tau phosphorylation in the cortex and hippocampus via AMPK/mTOR and PP2A, metformin increases insoluble tau species (including tau oligomers) and the number of inclusions with beta-sheet aggregates in the brain of P301S mice. In addition, metformin exacerbates hindlimb atrophy, increases P301S hyperactive behavior, induces tau cleavage by caspase 3 and disrupts synaptic structures. CONCLUSIONS: These findings indicate that metformin pro-aggregation effects mitigate the potential benefits arising from its dephosphorylating action, possibly leading to an overall increase of the risk of tauopathy in elderly diabetic patients. PMID- 26858122 TI - Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: a multicentre, phase 1b study. AB - BACKGROUND: PD-L1 and CTLA-4 immune checkpoints inhibit antitumour T-cell activity. Combination treatment with the anti-PD-L1 antibody durvalumab and the anti-CTLA-4 antibody tremelimumab might provide greater antitumour activity than either drug alone. We aimed to assess durvalumab plus tremelimumab in patients with advanced squamous or non-squamous non-small cell lung cancer (NSCLC). METHODS: We did a multicentre, non-randomised, open-label, phase 1b study at five cancer centres in the USA. We enrolled immunotherapy-naive patients aged 18 years or older with confirmed locally advanced or metastatic NSCLC. We gave patients durvalumab in doses of 3 mg/kg, 10 mg/kg, 15 mg/kg, or 20 mg/kg every 4 weeks, or 10 mg/kg every 2 weeks, and tremelimumab in doses of 1 mg/kg, 3 mg/kg, or 10 mg/kg every 4 weeks for six doses then every 12 weeks for three doses. The primary endpoint of the dose-escalation phase was safety. Safety analyses were based on the as-treated population. The dose-expansion phase of the study is ongoing. This study is registered with ClinicalTrials.gov, number NCT02000947. FINDINGS: Between Oct 28, 2013, and April 1, 2015, 102 patients were enrolled into the dose-escalation phase and received treatment. At the time of this analysis (June 1, 2015), median follow-up was 18.8 weeks (IQR 11-33). The maximum tolerated dose was exceeded in the cohort receiving durvalumab 20 mg/kg every 4 weeks plus tremelimumab 3 mg/kg, with two (30%) of six patients having a dose limiting toxicity (one grade 3 increased aspartate aminotransferase and alanine aminotransferase and one grade 4 increased lipase). The most frequent treatment related grade 3 and 4 adverse events were diarrhoea (11 [11%]), colitis (nine [9%]), and increased lipase (eight [8%]). Discontinuations attributable to treatment-related adverse events occurred in 29 (28%) of 102 patients. Treatment related serious adverse events occurred in 37 (36%) of 102 patients. 22 patients died during the study, and three deaths were related to treatment. The treatment related deaths were due to complications arising from myasthenia gravis (durvalumab 10 mg/kg every 4 weeks plus tremelimumab 1 mg/kg), pericardial effusion (durvalumab 20 mg/kg every 4 weeks plus tremelimumab 1 mg/kg), and neuromuscular disorder (durvalumab 20 mg/kg every 4 weeks plus tremelimumab 3 mg/kg). Evidence of clinical activity was noted both in patients with PD-L1 positive tumours and in those with PD-L1-negative tumours. Investigator-reported confirmed objective responses were achieved by six (23%, 95% CI 9-44) of 26 patients in the combined tremelimumab 1 mg/kg cohort, comprising two (22%, 95% CI 3-60) of nine patients with PD-L1-positive tumours and four (29%, 95% CI 8-58) of 14 patients with PD-L1-negative tumours, including those with no PD-L1 staining (four [40%, 95% CI 12-74] of ten patients). INTERPRETATION: Durvalumab 20 mg/kg every 4 weeks plus tremelimumab 1 mg/kg showed a manageable tolerability profile, with antitumour activity irrespective of PD-L1 status, and was selected as the dose for phase 3 studies, which are ongoing. FUNDING: MedImmune. PMID- 26858126 TI - Hospital Clostridium difficile Infection Rates and Prediction of Length of Stay in Patients Without C. difficile Infection. AB - BACKGROUND Inpatient length of stay (LOS) has been used as a measure of hospital quality and efficiency. Patients with Clostridium difficile infections (CDI) have longer LOS. OBJECTIVE To describe the relationship between hospital CDI incidence and the LOS of patients without CDI. DESIGN Retrospective cohort analysis. METHODS We predicted average LOS for patients without CDI at both the hospital and patient level using hospital CDI incidence. We also controlled for hospital characteristics (eg, bed size) and patient characteristics (eg, comorbidities, age). SETTING Healthcare Cost and Utilization Project Nationwide Inpatient Sample, 2009-2011. PATIENTS The Nationwide Inpatient Sample includes patients from a 20% sample of all nonfederal US hospitals. RESULTS Inpatient LOS was significantly longer (P<.001) at hospitals with greater CDI incidence at both the hospital and individual level. At a hospital level, a percentage point increase in the CDI incidence rate was associated with more than an additional day's stay (between 1.19 and 1.61 days). At the individual level, controlling for all observable variables, a percentage point increase in the CDI incidence rate at their hospital was also associated with longer LOS (between 0.6 and 1.05 additional days). Hospital CDI incidence had a larger impact on LOS than many other commonly used predictors of LOS. CONCLUSION CDI rates are a predictor of LOS in patients without CDI at an individual and institutional level. CDI rates are easy to measure and report and thus may provide an important marker for hospital efficiency and/or quality. PMID- 26858124 TI - Infusion of CD3/CD28 costimulated umbilical cord blood T cells at the time of single umbilical cord blood transplantation may enhance engraftment. AB - Limited cell numbers in umbilical cord blood (UCB) grafts present a major impediment to favorable outcomes in adult transplantation, largely related to delayed or failed engraftment. The advent of UCB transplantation (UCBT) using two grafts successfully circumvents this obstacle, despite the engraftment of only one unit. Preclinical models suggested that the addition of UCB T cells at the time of transplant can enhance engraftment. We tested whether ex vivo activation by CD3/CD28 costimulation and expansion of T cells from a single UCB graft would be safe and feasible in adults with advanced hematologic malignancies, with an overall objective of optimizing engraftment in single unit UCBT. In this phase 1 study, recipients of single UCB units were eligible if the unit was stored in two adequate fractions. Dose limiting toxicity was defined as grade 3 or grade 4 GVHD within 90 days of UCBT. Four patients underwent UCBT; all were treated at the first dose level (10(5) cells/kg). At the 10(5) cells/kg dose level two subjects experienced grade 3 intestinal GVHD, thus meeting stopping criteria. For three subjects, neutrophil engraftment was early (12, 17, and 20 days), while one subject experienced primary graft failure. We observed early donor T cell trafficking and found that expanded T cells produced supraphysiologic levels of cytokines relevant to engraftment and to lymphoid differentiation and function. Taken together, these preliminary data suggest rapid engraftment in recipients of a single UCBT combined with relatively low doses of activated T cells, though potentially complicated by severe GVHD. PMID- 26858127 TI - Towards ultrasensitive malaria diagnosis using surface enhanced Raman spectroscopy. AB - We report two methods of surface enhanced Raman spectroscopy (SERS) for hemozoin detection in malaria infected human blood. In the first method, silver nanoparticles were synthesized separately and then mixed with lysed blood; while in the second method, silver nanoparticles were synthesized directly inside the parasites of Plasmodium falciparum. It was observed that the first method yields a smaller variation in SERS measurements and stronger correlation between the estimated contribution of hemozoin and the parasitemia level, which is preferred for the quantification of the parasitemia level. In contrast, the second method yields a higher sensitivity to a low parasitemia level thus could be more effective in the early malaria diagnosis to determine whether a given blood sample is positive. PMID- 26858128 TI - Systematic review with meta-analysis: faecal occult blood tests show lower colorectal cancer detection rates in the proximal colon in colonoscopy-verified diagnostic studies. AB - BACKGROUND: The performance of faecal occult blood tests (FOBTs) to screen proximally located colorectal cancer (CRC) has produced inconsistent results. AIM: To assess in a meta-analysis, the diagnostic accuracy of FOBTs for relative detection of CRC according to anatomical location of CRC. METHODS: Diagnostic studies including both symptomatic and asymptomatic cohorts assessing performance of FOBTs for CRC were searched from MEDINE and EMBASE. Primary outcome was accuracy of FOBTs according to the anatomical location of CRC. Bivariate random effects model was used. Subgroup analyses were performed to evaluate test performance of guaiac-based FOBT (gFOBT) and immunochemical-based FOBT (iFOBT). RESULTS: Thirteen studies, with 17 cohorts, reporting performance of FOBT were included; a total of 26 342 patients (mean age 58.9 years; 58.1% male) underwent both colonoscopy and FOBT. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of FOBTs for CRC detection in the proximal colon were 71.2% (95% CI 61.3-79.4%), 93.6% (95% CI 90.7-95.7%), 11.1 (95% CI 7.8 15.8) and 0.3 (95% CI 0.2-0.4) respectively. Corresponding findings for CRC detection in distal colon were 80.1% (95% CI 70.9-87.0%), 93.6% (95% CI 90.7 95.7%), 12.6 (95% CI 8.8-18.1) and 0.2 (95% CI 0.1-0.3). The area-under-curve for FOBT detection for proximal and distal CRC were 90% vs. 94% (P = 0.0143). Both gFOBT and iFOBT showed significantly lower sensitivity but comparable specificity for the detection of proximally located CRC compared with distal CRC. CONCLUSION: Faecal occult blood tests, both guaiac- and immunochemical-based, show better diagnostic performance for the relative detection of colorectal cancer in the distal colon than in the proximal bowel. PMID- 26858125 TI - Self-renewal of CD133(hi) cells by IL6/Notch3 signalling regulates endocrine resistance in metastatic breast cancer. AB - The mechanisms of metastatic progression from hormonal therapy (HT) are largely unknown in luminal breast cancer. Here we demonstrate the enrichment of CD133(hi)/ER(lo) cancer cells in clinical specimens following neoadjuvant endocrine therapy and in HT refractory metastatic disease. We develop experimental models of metastatic luminal breast cancer and demonstrate that HT can promote the generation of HT-resistant, self-renewing CD133(hi)/ER(lo)/IL6(hi) cancer stem cells (CSCs). HT initially abrogates oxidative phosphorylation (OXPHOS) generating self-renewal-deficient cancer cells, CD133(hi)/ER(lo)/OXPHOS(lo). These cells exit metabolic dormancy via an IL6-driven feed-forward ER(lo)-IL6(hi)-Notch(hi) loop, activating OXPHOS, in the absence of ER activity. The inhibition of IL6R/IL6-Notch pathways switches the self-renewal of CD133(hi) CSCs, from an IL6/Notch-dependent one to an ER dependent one, through the re-expression of ER. Thus, HT induces an OXPHOS metabolic editing of luminal breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133(hi)/ER(lo) cells mediating metastatic progression, which is sensitive to dual targeted therapy. PMID- 26858129 TI - Site disparities in apoptotic variants as predictors of risk for second primary malignancy in patients with squamous cell carcinoma of the head and neck. AB - BACKGROUND: FAS/FASL promoter variants are considered in altering transcriptional activity of those genes and consequently alter regulation of cell death. However, no studies have investigated whether tumor sites contribute to the association between FAS/FASL polymorphisms and risk for second primary malignancy (SPM). METHOD: In this study, FAS670 A > G, FAS1377 G > A, FASL124 A > G, and FASL844C > T polymorphisms were genotyped in 752 OPC and 777 non-OPC patients. Both univariate and multivariable cox proportional hazard models were used to assess the associations. RESULTS: The univariate and multivariable analyses showed that patients with index OPC and FASL844 CT/TT genotype had significantly increased risk of SPM (cHR, 2.5; 95% CI, 1.1-5.8, P = 0.043 and aHR, 2.7; 95% CI, 1.2-6.0, P = 0.032) compared with those with FASL844 CC genotype as the reference group, while index non-OPC patients with FAS670 AG/GG and FasL844 CT/TT genotypes had significantly increased risk of SPM (cHR, 2.2 and 1.8; 95% CI, 1.2-5.7 and 1.1 3.2; and P = 0.04 and 0.041, respectively and aHR, 2.4 and 1.7; 95% CI, 1.1-5.1 and 1.0-3.0; and P = 0.043 and 0.049, respectively) compared with their corresponding AA and CC genotypes . Moreover, patients carrying more FAS/FASL variants significantly increased risk of SPM among index non-OPC patients. The stratified analysis showed that smoking status differently modified the associations between FAS/FASL polymorphisms and risk of SPM among index non-OPC from OPC patients. CONCLUSION: These results suggested that FAS/FASL polymorphisms might significantly modify SPM risk among patients with SCCHN in a tumor site-specific manner. PMID- 26858130 TI - Complete Genomic Sequence of Bacteriophage H188: A Novel Vibrio kanaloae Phage Isolated from Yellow Sea. AB - Phage H188, a novel Vibrio kanaloae phage, was isolated from the surface water of Yellow Sea. Morphological analysis by transmission electron microscopy reveals that it belongs to the family Myoviridae. Present result suggests that the phage is stable at pH between 4.0 and 12.0. No significant difference in phage titers is noted at temperature 30-50 degrees C. A latent period of approximately 96 mins is indicated by the one-step growth curve. And, the burst size is about three virions per cell. Furthermore, genomic analysis of H188 reveals a genome size of 50364 bp with 43.63 % G+C content, and 76 putative open reading frames. There is no obvious similarity between H188 and other known phages by genomic comparison. Moreover, the H188 genome includes modules for phage structure, phage packaging, DNA replication and regulation, and some additional functions. PMID- 26858131 TI - Transcriptional Profiling Analysis of Bacillus subtilis in Response to High Levels of Fe(3.). AB - Iron is essential to microorganisms for its important biological function but could be highly toxic in excess. We have used genome-wide transcriptional analysis in Fe(3+)-treated (4 mM) Bacillus subtilis to reveal the effect of excess Fe(3+) on B. subtilis and characterized the potential pathways involved in Fe(3+) stress tolerance. A total of 366 and 400 genes were identified as significantly up-regulated and down-regulated, respectively. We found excess Fe(3+) had four major influences on B. subtilis: Fe(3+) resulted in oxidative stress and induced genes involved in oxidative stress resistance including the SigB-regulated genes, but the PerR regulon was not inducible in Fe(3+)-mediated oxidative stress except zosA; Fe(3+) significantly disturbed homeostasis of Mn(2+) and Zn(2+), and the mechanism was proposed in this article; the acidity of Fe(3+)-induced genes involved in acid consuming and production of bases and shifted B. subtilis to carbon starvation state; Fe(3+)-induced genes related to membrane remodeling (bkd operon), which prevents Fe(3+)'s incorporation to membrane lipids. Moreover, Fe(3+) repressed the stringent control response, consistent with the induction of stringent control in iron limitation, demonstrating that iron might be a signal in stringent control of B. subtilis. This study was the first to provide a comprehensive overview of the genetic response of B. subtilis to ecxess Fe(3+). PMID- 26858132 TI - Altererythrobacter estronivorus sp. nov., an Estrogen-Degrading Strain Isolated from Yundang Lagoon of Xiamen City in China. AB - A novel gram-negative, non-spore-forming, mobile, estrogen-degrading strain, MH B5(T), was isolated from Yundang Lagoon in Xiamen city of China. Growth of this strain occurred between 4 and 40 degrees C (optimum at 35 degrees C), pH 5.5 10.0 (7.5), 0.0-7 % NaCl (1-2 %). Phylogenetic analysis based on 16S rRNA gene sequence showed that strain MH-B5(T) belonged to the genus Altererythrobacter family Erythrobacteraceae, showing the highest sequence similarity (96.6 %) to Altererythrobacter xinjiangensis S3-63(T). The dominant cellular fatty acid was C18:1 omega7c and/or C18:1 omega6c (57.98 %). The major respiratory quinone was ubiquinone 10, and major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipid, phospholipid, and phosphatidylcholine. Strain MH-B5(T) did not contain bacteriochlorophyll a. The draft genome sequence of strain MH-B5(T) comprised about 3.67 Mb, with an average G+C content of 60 mol%. On the basis of data from its morphology, chemotaxonomy, 16S rRNA gene sequence and genome sequence, strain MH-B5(T) represents a novel species, for which the name Altererythrobacter estronivorus sp. nov., is proposed. The type strain is MH-B5(T) (=CCTCC AB2012025(T)=DSM 25986(T)). PMID- 26858133 TI - The Biodiversity Changes in the Microbial Population of Soils Contaminated with Crude Oil. AB - Crude oil spills resulting from excavation, transportation and downstream processes can cause intensive damage to living organisms and result in changes in the microbial population of that environment. In this study, we used a pyrosequencing analysis to investigate changes in the microbial population of soils contaminated with crude oil. Crude oil contamination in soil resulted in the creation of a more homogenous population of microorganisms dominated by members of the Actinomycetales, Clostridiales and Bacillales (all belonging to Gram-positive bacteria) as well as Flavobacteriales, Pseudomonadales, Burkholderiales, Rhizobiales and Sphingomonadales (all belonging to Gram-negative bacteria). These changes in the biodiversity decreased the ratios of chemoheterotrophic bacteria at higher concentrations of crude oil contamination, with these being replaced by photoheterotrophic bacteria, mainly Rhodospirillales. Several of the dominant microbial orders in the crude oil contaminated soils are able to degrade crude oil hydrocarbons and therefore are potentially useful for remediation of crude oil in contaminated sites. PMID- 26858134 TI - Dermatologic findings of focal dermal hypoplasia (Goltz syndrome). AB - Goltz syndrome, caused by mutations in PORCN, is an X-linked dominant ectodermal dysplasia which is also known as focal dermal hypoplasia. This name is derived from the predominant pathologic skin findings of the syndrome. Nineteen Goltz affected participants attended a multidisciplinary scientific and clinical conference convened by the National Foundation for Ectodermal Dysplasia which allowed further characterization of the features of this very rare condition. At birth, the affected areas of skin are typically erythematous and fragile. The hallmark cutaneous features, which vary widely due to mosacism and X inactivation, include the previously described skin changes of asymmetric Blaschko-linear and reticulated atrophy, pigmentary changes, and telangectasias. Lipomatous changes and papillomas as characteristically defined were reported in the majority of patients. A newly recognized skin finding was progressive hyperpigmented freckling that occurred within the hypopigmented areas which were noted to be photosensitive. Many patients also had a pebbly texture to the central face, dorsal hands and feet. Punctate erosions within the atrophic areas and hypohidrosis were also common. Most had patchy alopecia and many had diffusely thin hair. Scanning electron microscopy of the hair shafts revealed abnormalities in the majority of participants with several different features identified, including atrophic hairs with reduced diameters, markedly flattened hairs as noted in cross-sectional views, trichorrhexis nodosa, pili torti, and pili trianguli et canaliculi. Nail changes included V-nicking and longitudinal ridging of the nail plate, in addition to micronychia. Early recognition of the dermatologic features, in addition to the variable but universal limb anomalies, of Goltz syndrome will allow early and accurate diagnosis without the need for extensive diagnostic studies, while also allowing for accurate prognosis and appropriate genetic counseling. PMID- 26858136 TI - Predictors of cardiac rehabilitation attendance following primary percutaneous coronary intervention for ST-elevation myocardial infarction in Australia. AB - Cardiac rehabilitation is an important component of recovery and secondary prevention following urgent primary percutaneous coronary intervention. However, attendance and factors that predict participation by patients admitted with ST elevation myocardial infarction remain unclear. This Australian study was conducted using a descriptive, comparative design. Consecutive patients (n = 246) at two hospitals were interviewed by telephone at four weeks and six months. Open ended questions were used to assess cardiac rehabilitation attendance, sociodemographics, modifiable risk factors, clinical outcomes, and post-discharge health support. Post-discharge home visits at four weeks (odds ratio: 2.64, 95% confidence interval: 1.48-4.71) and at six months were associated with better cardiac rehabilitation attendance; more males participated at four weeks and at six months. The results suggest the need to integrate post-discharge health support with cardiac rehabilitation to facilitate recovery after primary percutaneous coronary intervention, particularly for females with ST-elevation myocardial infarction. PMID- 26858135 TI - The added prognostic value of MRI findings for recovery in patients with low back pain in primary care: a 1-year follow-up cohort study. AB - PURPOSE: Information on the prognostic value of MRI findings in low back pain patients in primary care is lacking. The objective of this study is to investigate the added prognostic value of baseline MRI findings over known prognostic factors for recovery at 12-month follow-up in patients with low back pain referred to MRI by their general practitioner. METHODS: Patients referred by their general practitioner for MRI of the lumbar spine were recruited at the MRI Center. The questionnaires at baseline and at 3 and 12-months follow-up included potential clinical predictors from history taking and the outcome recovery. The MRI radiology reports were scored. Analysis was performed in 3 steps: derivation of a predictive model including characteristics of the patients and back pain only (history taking), including reported MRI findings only, and the addition of reported MRI findings to the characteristics of the patients and back pain. RESULTS: At 12-months follow-up 53% of the patients reported recovery (n = 683). Lower age, better attitude/beliefs regarding back pain, acute back pain, presence of neurological symptoms of the leg(s), and presence of non-continuous back pain were significantly associated with recovery at 12-months follow-up: area under the curve (AUC) 0.77. Addition of the MRI findings resulted in an AUC of 0.78. CONCLUSIONS: At 12-months follow-up, only 53% of these patients with low back pain referred for MRI in general practice reported recovery. Five clinic baseline characteristics were associated with recovery at 12-months follow-up; adding the MRI findings did not result in a stronger prediction of recovery. PMID- 26858137 TI - The phosphocarrier protein HPr of Neisseria meningitidis interacts with the transcription regulator CrgA and its deletion affects capsule production, cell adhesion, and virulence. AB - The bacterial phosphotransferase system (PTS) transports and phosphorylates sugars, but also carries out numerous regulatory functions. The beta proteobacterium Neisseria meningitidis possesses an incomplete PTS unable to transport carbon sources because it lacks a membrane component. Nevertheless, the residual phosphorylation cascade is functional and the meningococcal PTS was therefore expected to carry out regulatory roles. Interestingly, a DeltaptsH mutant (lacks the PTS protein HPr) exhibited reduced virulence in mice and after intraperitoneal challenge it was rapidly cleared from the bloodstream of BALB/c mice. The rapid clearance correlates with lower capsular polysaccharide production by the DeltaptsH mutant, which is probably also responsible for its increased adhesion to Hec-1-B epithelial cells. In addition, compared to the wild type strain more apoptotic cells were detected when Hec-1-B cells were infected with the DeltaptsH strain. Coimmunoprecipitation revealed an interaction of HPr and P-Ser-HPr with the LysR type transcription regulator CrgA, which among others controls its own expression. Moreover, ptsH deletion caused increased expression of a PhicrgA-lacZ fusion. Finally, the presence of HPr or phospho-HPr's during electrophoretic mobility shift assays enhanced the affinity of CrgA for its target sites preceding crgA and pilE, but HPr did not promote CrgA binding to the sia and pilC1 promoter regions. PMID- 26858138 TI - Analysis of hepatitis B virus genotype changes in patients with chronic hepatitis B infection on tenofovir therapy. AB - Antiviral therapy for chronic hepatitis B (CHB) is often required for prolonged periods. We investigated the instance of one HBV genotype switching to another during tenofovir therapy. Of the 67 patients, genotype A was present in 6 (8.9%), D in 43 (65.6%), C in 1 (1.5%), and mixed in 17 (23.8%) patients. Genotype changes were detected in 51 (76.1%) patients on therapy during a follow-up of 192 (range 52-312) weeks. Inter-genotype changes were seen in 17 (33.3%) and intra genotype in 28 (55%) and both inter- and intra-genotype in 6 of 51 (11.7%) patients. The distribution of genotypes in patients achieving complete virological response was genotype D, 32/43 (74.4%); genotype A, 6/6 (100%); and mixed genotypes, 13/17 (76.47%). The cumulative time of genotype switch among genotype A was 12 months (range 6-18), in genotype D, 12 months (range 6-48), and mixed genotype, 18 months (range 6-24). The type of inter-genotype switch most frequently detected among genotype A1 was from A1 to D1 5/6 (83.3%), followed by mixed to genotype D3 7/13 (54%) and among intra-genotype changes, from D1 to D3 in 14/20 (70%). Pretreatment HBV genotype was the only factor predicting inter genotype switches with genotype A or mixed genotypes more likely to undergo inter genotype switches as compared to genotype D patients (OR 66.6 [13.6-327.0, P < 0.001]). Compared to genotype D, genotype A, and mixed genotypes are more inclined to switch while on tenofovir therapy. Genotypes tend to switch and select to a particular type possibly due to constant antiviral drug pressure. J. Med. Virol. 88:1364-1375, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26858139 TI - Palladium-Catalyzed Oxidative Synthesis of Unsymmetrical Azophenols. AB - A straightforward palladium-catalyzed oxidative hydroxylation of azobenzenes is reported. The developed methodology tolerates various functional groups and allows the synthesis of diverse unsymmetrical azophenols under mild conditions in good to excellent yields. A complementary procedure was also investigated by in situ generation of PIFA. This study represents the first general method for the synthesis of o-hydroxyazobenzenes starting from simple azoarenes. PMID- 26858140 TI - Doing More Than Caring About Quality. AB - The treatment of chronically ill patients with end stage renal disease (ESRD) receiving dialysis therapies has advanced greatly over the years and accomplished many successes in prolonging the life of patients with ESRD, yet has had considerable failures due to the inability to compensate for all functions of the kidneys. In addition, the focus to achieve quality goals for laboratories and vascular access measures may indicate a good quality of care from providers, but meeting these clinical and physiological goals may not fully maximize individual benefit to a patient, may not be aligned with the patient's care goals, and could conceivably impact negatively the patient's experience of care and quality of life. The age of individualized patient centered care is forthcoming with advancements in technology and our understanding of the treatment of renal diseases. The future holds promise for enhancing the quality provided to each patient but will require nephrologists to overcome numerous hurdles. This article provides an opinion on principles that may fundamentally improve the quality of renal disease care in the future and represents themes that can enhance quality, safety, and efficiency in the health care delivery system. It is believed that quality measured from a patient centric perspective will shift the treatment for these chronic disorders to better meet each patient's needs and goals, while evolving an enhanced delivery system for the care of all ESRD patients. PMID- 26858141 TI - 3D transthoracic echocardiography to assess pulmonary valve morphology and annulus size in patients with Tetralogy of Fallot. AB - BACKGROUND: Accurate evaluation of the pulmonary valve (PV) is crucial before surgical repair of Tetralogy of Fallot (TOF). AIMS: To assess PV and pulmonary annulus (PA) morphology using three-dimensional (3D) transthoracic echocardiography (TTE) in infants referred for surgical repair of TOF. Also, to compare PA measurements obtained by 3D TTE with those from other imaging modalities, including two-dimensional (2D) TTE and computed tomography (CT), with reference to surgical measurements. METHODS: 3D zoom mode was used to assess PV morphology. 2D TTE and CT PA diameters were compared to both vertical and horizontal diameters obtained from 3D datasets. Surgical PA diameters were measured using Hegar's dilators. RESULTS: A total of 29 patients with TOF (median [range] age 6 [3-24] months) were included and all successfully underwent 2D and 3D TTE; 22 also underwent CT. The number of pulmonary leaflets could be visualized in 24 patients (82.8%), with complete concordance with surgical findings. Vertical diameter was significantly longer than horizontal diameter (P<0.001)-underlying PA eccentricity-and was more important in bicuspid than tricuspid valves. Correlations between 2D and 3D TTE diameters were good. Surgical diameter was better correlated with 2D and 3D diameters than with CT diameter. 3D minimum, 2D and CT diameters were significantly lower than surgical diameters, but 3D mean and maximum diameters were not. CONCLUSION: 3D TTE is accurate to assess PV morphology and PA size in patients with TOF. 2D TTE and CT underestimate PA diameter with reference to surgical diameter, however 3D mean and maximum diameters did not differ significantly. PMID- 26858142 TI - Cardiac imaging of congenital heart diseases during interventional procedures continues to evolve: Pros and cons of the main techniques. AB - Cardiac catheterization has contributed to the progress made in the management of patients with congenital heart disease (CHD). First, it allowed clarification of the diagnostic assessment of CHD, by offering a better understanding of normal cardiac physiology and the pathophysiology and anatomy of complex malformations. Then, it became an alternative to surgery and a major component of the therapeutic approach for some CHD lesions. Nowadays, techniques have evolved and cardiac catheterization is widely used to percutaneously close intracardiac shunts, to relieve obstructive valvar or vessel lesions, and for transcatheter valve replacement. Accurate imaging is mandatory to guide these procedures. Cardiac imaging during catheterization of CHD must provide accurate images of lesions, surrounding cardiac structures, medical devices and tools used to deliver them. Cardiac imaging has to be 'real-time' with an excellent temporal resolution to ensure 'eyes-hands' synchronization and 'device-target area' accurate positioning. In this comprehensive review, we provide an overview of conventional cardiac imaging tools used in the catheterization laboratory in daily practice, as well as the effect of recent evolution and future imaging modalities. PMID- 26858143 TI - Early TIPS versus endoscopic therapy for secondary prophylaxis after management of acute esophageal variceal bleeding in cirrhotic patients: a meta-analysis of randomized controlled trials. AB - BACKGROUND AND AIMS: American College of Gastroenterology and American Association for the Study of Liver Disease guidelines recommend endoscopic and pharmacologic treatment for esophageal variceal bleed. Transjugular intrahepatic portosystemic shunt (TIPS) placement is reserved for cases of therapeutic failure. Several studies have suggested improved prevention of rebleeding and improved survival without excess hepatic encephalopathy in patients who receive TIPS within the first 5 days after bleeding (early TIPS). In this meta-analysis, we evaluated the safety and efficacy of early TIPS versus endoscopic therapy for secondary prophylaxis after acute esophageal variceal bleeding in cirrhotic patients. METHODS: Pubmed, Medline, Embase, ClinicalTrials.gov, and ISI Web of Science were searched for randomized controlled trials that compared early TIPS to endoscopic therapy. The primary outcome was mortality at 1 year; secondary outcomes were rebleeding and hepatic encephalopathy at 1 year. RESULTS: Nine randomized controlled trials involving 608 cirrhotic patients were identified. Early TIPS was associated with a significant risk reduction in 1-year mortality (RR, 0.68; 95% CI, 0.49-0.96; P = 0.03) and 1-year incidence of variceal rebleeding (RR, 0.28; 95% CI, 0.20-0.40; P < 0.001) without significant heterogeneity among studies (I(2) = 30% and 47%, respectively). No significant difference in the incidence of hepatic encephalopathy at 1 year was observed (RR, 1.36; 95% CI, 0.72-2.56; P = 0.34); however, there was significant heterogeneity among studies (I(2) = 68%). CONCLUSION: TIPS placed within 5 days after a major esophageal variceal hemorrhage is superior to endoscopic treatment in reducing subsequent bleeding. Early TIPS placement is also associated with superior 1-year survival without significantly increasing the incidence of hepatic encephalopathy. PMID- 26858144 TI - Long-chain saturated and monounsaturated fatty acids associate with development of premature infants up to 18 months of age. AB - Myelination is important perinatally and highly dependent on long-chain saturated and monounsaturated fatty acids. Long-chain polyunsaturated fatty acids, nowadays often supplemented, inhibit oleic acid synthesis. Using data from a premature cohort, we studied if nervonic, lignoceric and oleic acids correlated to growth and early development up to 18 months corrected age. Small for gestational age infants had lower concentrations than infants appropriate for gestational age. Only oleic acid was negatively correlated to long-chain polyunsaturated fatty acids. Oleic and lignoceric acids correlated to social interaction at one month, and nervonic acid to mental, psychomotor and behavioral development at 6, 10 and 18 months, also when adjusted for several confounders. Negative association between oleic acid and long-chain polyunsaturated fatty acids suggests inhibition of delta-9 desaturase, and nervonic acid's divergent correlation to lignoceric and oleic acids suggests different metabolism in neonatal period. Our results may have implications for the supplementation of premature infants. PMID- 26858145 TI - Conducting omega-3 clinical trials with cardiovascular outcomes: Proceedings of a workshop held at ISSFAL 2014. AB - In contrast to earlier long-chain (LC) omega-3 (i.e. EPA and DHA) investigations, some recent studies have not demonstrated significant effects of EPA and DHA on cardiovascular disease (CVD) outcomes. The neutral findings may have been due to experimental design issues, such as: maintenance on aggressive cardiovascular drug treatment overshadowing the benefits of LC omega-3s, high background LC omega-3 intake, too few subjects in the study, treatment duration too short, insufficient LC omega-3 dosage, increase in omega-6 fatty acid intake during the study, failure to assess the LC omega-3 status of the subjects prior to and during treatment and lack of clarity concerning which mechanisms were expected to produce benefits. At the 11th ISSFAL Congress, a workshop was held on conducting LC omega-3 clinical trials with cardiovascular outcomes, with the goal of gaining a better understanding concerning aspects of experimental design that should be considered when planning clinical studies related to EPA and DHA and potential cardiovascular benefits. PMID- 26858146 TI - Resolvin D3 multi-level proresolving actions are host protective during infection. AB - Resolution of infection and inflammation is governed by innate immune cells. The resolvin family of n-3 mediators produced by resolving exudates stimulates clearance of neutrophils and attenuates pro-inflammatory signals. Using metabololipidomics, endogenous resolvin D3 (RvD3) was identified in self resolving exudates during active E. coli infection. Through a new, independent synthetic route for RvD3, we matched endogenous and synthetic RvD3 and determined that RvD3 (ng doses) potently reduced the resolution interval (Ri) by ~4.5h during E. coli peritonitis after administration at peak inflammation (Tmax=12h) and increased leukocyte phagocytosis of E. coli and neutrophils as well as reduced proinflammatory cytokines, chemokines, MMP-2 and MMP-9. At pM-nM concentrations, RvD3 also enhanced human macrophage efferocytosis and bacterial phagocytosis, increased neutrophil bacterial phagocytosis and intracellular ROS generation, and reduced human platelet-PMN aggregation. These results provide additional evidence for potent RvD3 immunoresolvent actions in host defense, host protection and antimicrobial defense. PMID- 26858147 TI - Spatial Electron-hole Separation in a One Dimensional Hybrid Organic-Inorganic Lead Iodide. AB - The increasing efficiency of the inorganic-organic hybrid halides has revolutionised photovoltaic research. Despite this rapid progress, the significant issues of poor stability and toxicity have yet to be suitably overcome. In this article, we use Density Functional Theory to examine (Pb2I6) . (H2DPNDI) . (H2O) . (NMP), an alternative lead-based hybrid inorganic-organic solar absorber based on a photoactive organic cation. Our results demonstrate that optical properties suitable for photovoltaic applications, in addition to spatial electron-hole separation, are possible but efficient charge transport may be a limiting factor. PMID- 26858148 TI - Evaluation of facilitative factors for preventing cognitive decline: A 3-year cohort study of community intervention. AB - AIM: We conducted a cohort study to elucidate paticipants' facilitative factors that may help to prevent cognitive decline. METHODS: This study followed 100 participants (average age: 74.1 +/- 5.8; 10 men, 90 women) for 3 years; participants had previously been part of the Taketoyo Project (n = 366) in 2007 2011. The end-point was defined as reduced cognitive function in elderly community residents participating in a preventive intervention for dementia. The presence or absence of reduced cognitive function at the end of the third year of intervention was the dependent variable, and all evaluation items were considered explanatory variables. After Fisher's exact test (P < 0.15), stepwise multiple logistic regression analysis (P < 0.05) was performed, and facilitative factors for prevention of cognitive decline were extracted. RESULTS: Items with a significant adjusted odds ratio (OR) based on multiple logistic regression analysis were the three-word delayed recall test (OR: 0.330, 95% confidence interval (CI): 0.142-0.767; P < 0.05), word fluency (OR: 0.565, 95%CI: 0.359 0.891; P < 0.05), frequency of going out (OR: 2.790, 95%CI: 0.803-6.380; P < 0.05) and number of friends with whom they engaged in activities (OR:0.344, 95%CI: 0.127-0.932; P < 0.05). CONCLUSION: Subjects who had maintained a certain level of cognitive function, engaged in activities with friends, and went out frequently at baseline were extracted. In other words, the results suggested that enhancement of social networks and leisure activities prompted by recreational centre participation had a positive effect on maintaining cognitive function. The results also suggest that to improve the effectiveness of preventive interventions for cognitive dysfunction, support for social factors and leisure activities, in addition to cognitive function, may improve the long-term effectiveness of maintaining cognitive function. PMID- 26858150 TI - Evaluation of Peel PlateTM EC for Determination of E. coli and Coliform or Total Coliform in Dairy Products. AB - Peel PlateTM EC is a low-profile plastic, 47 mm culture dish with an adhesive top that contains a dried medium with Gram-negative selective agents and with enzyme substrate indicators for beta-galactosidase (coliform) and beta-glucuronidase (Escherichia coli). The method provides a conventional quantitative coliform (red) and E. coli (blue/purple/black) count with simple rehydration and incubation for 24 +/- 2 h at 35 +/- 1 degrees C, while providing a total coliform result, sum of E. coli, and coliform without color differential in dairy products at 32 +/- 1 degrees C for 24 +/- 2 h. Dairy matrixes claimed and supported with total coliform data are whole milk, skim milk, chocolate milk (2% fat), heavy cream (35% fat), pasteurized whole goat milk, ultra-high-temperature pasteurized milk, powdered milk, lactose-reduced milk, strawberry milk, shredded cheddar cheese, raw cow milk, raw goat milk, raw sheep milk, sour cream, condensed milk, eggnog, vanilla ice cream, condensed whey, yogurt, and cottage cheese. Matrixes claimed for E. coli and total coliform detection are raw ground beef, mixed cellulose 0.45 MUm filtered bottled water, environmental sponge of stainless steel, raw ground turkey, dry dog food, liquid whole pasteurized eggs, milk chocolate, leafy green (mixed greens) rinse/flume water, irrigation water, poultry carcass rinse, and large animal carcass sponge. The method has been independently evaluated for total coliform in whole milk, skim milk, chocolate milk, and heavy cream. The method was also independently evaluated for E. coli and coliform in ground beef, filtered bottled water, and sponge rinse from stainless steel surfaces. In inclusivity and exclusivity studies, the method detected 57 of 58 different strains of coliform and E. coli at 32 +/- 1 degrees C and 35 +/- 1 degrees C in and excluded 31 of 32 different noncoliform strains consisting of Gram-negative and Gram-positive bacteria. In the matrix study, each matrix was assessed separately at each contamination level in comparison to an appropriate reference method. Colony counts were determined for each level and then log10 transformed. The transformed data were evaluated for repeatability, log-mean comparison between methods with 95% confidence interval, and r(2). A 95% confidence interval range of -0.5 to 0.5 on the mean difference was used as the acceptance criterion to establish significant statistical difference between methods. The evaluations demonstrate that the Peel Plate EC method provides no statistical differences across most of the matrixes. The coliform r(2) values were greater than 0.9 except in the case of skim milk (r(2) = 0.77 and 0.69), sheep milk (0.84), and chocolate (0.81). In the case of skim milk, the three highest concentrations were significantly biased low compared with the reference method, whereas in the case of chocolate, the highest concentration was significantly biased high. The E. coli r(2) values were greater than 0.9 except in the case of hog rinse (0.89), flume water (0.82), and chocolate (0.77). The lower values were generally from only a 1 log difference between highest and lowest concentrations except in the case of chocolate, in which the highest concentration was biased high compared with the reference method. Within-method repeatability of Peel Plate EC was similar to the reference method, with relative SDs generally less than 5% when log10 means were >=1.5. QC data support that the Peel Plate EC is stable for 1 year when refrigerated. Incubation temperature ranges, 30-36 degrees C, and times, 22-26 and 48 h for yogurt, were not significantly different in paired t-test comparison. The method is selective without the need for confirmation, although confirmation of coliform and E. coli was performed as part of the validation work. PMID- 26858151 TI - Quantifying the cooperative subunit action in a multimeric membrane receptor. AB - In multimeric membrane receptors the cooperative action of the subunits prevents exact knowledge about the operation and the interaction of the individual subunits. We propose a method that permits quantification of ligand binding to and activation effects of the individual binding sites in a multimeric membrane receptor. The power of this method is demonstrated by gaining detailed insight into the subunit action in olfactory cyclic nucleotide-gated CNGA2 ion channels. PMID- 26858152 TI - Positive Clinical Outcomes Are Synergistic With Positive Educational Outcomes When Using Telehealth Consulting in General Practice: A Mixed-Methods Study. AB - BACKGROUND: The use of telehealth technology to enable real-time consultations between patients and specialist services (to whom travel may be an impediment to the patient's care) has recently been encouraged in Australia through financial incentives. However, the uptake has been both fragmented and inconsistent. The potential benefits for patients include access to a broader range of specialist referral services, cost and time saving, and more rapid access to specialist services and a continuum of care through the triangulation of interaction between patient, primary health care providers (general practitioners and nurses), and specialists. Enhanced broadband connectivity and higher-grade encryption present an opportunity to trial the use of telehealth consulting as an intrinsic element of medical education for both medical students and doctors-in-training within rural practices and Aboriginal Medical Services. OBJECTIVE: This paper discusses the reported, and varied, benefits of telehealth consulting arising from a multisite trial in New South Wales, Australia. The purpose of this study is to encourage the use of selected telehealth consultations between patients in a primary care setting with a specialist service as an integral aspect of medical education. METHODS: The trial closely followed the protocol developed for this complex and multiaspect intervention. This paper discusses one aspect of the research protocol--using telehealth consultations for medical education--in detail. RESULTS: Qualitative and quantitative analyses were conducted. In the quantitative analysis, free-text comments were made on aspects of Telehealth Consulting for the patient, concerning the quality of the interactions, and the time and cost saving, and also on the leaning opportunities. Students commented that their involvement enhanced their learning. All respondents agreed or strongly agreed that that the interpersonal aspects were satisfactory, with some brief comments supporting their views. In the analysis of the qualitative data, five themes emerged from the analyses concerning the educational benefits of Telehealth Consulting for different levels of learners, while three themes were identified concerning clinical benefits. CONCLUSIONS: The results demonstrated strong synergies between the learning derived from the telehealth consulting and the clinical benefits to the patient and clinicians involved. PMID- 26858153 TI - miR-373 Inhibits Glioma Cell U251 Migration and Invasion by Down-Regulating CD44 and TGFBR2. AB - Glioblastoma multiforme (GBM) is the most malignant glioma, unveiling the underlying mechanisms of its aggressiveness could promote the discovery of potential targets for effective treatment. MicroRNAs (miRNAs) are important participants in both development and disease, its involvement in cancers has long been recognized. In this study, we investigated the role of miRNA-373 (miR-373) in GBM cell line U251, demonstrated that although miR-373 does not affect cell growth of U251, it inhibits migration and invasion of U251. Forced expression of miR-373 down-regulates the expressions CD44 and TGFBR2, while knockdown of CD44 and TGFBR2 presents the similar phenotype as miR-373 overexpression, suggesting that CD44 and TGFBR2 are functional targets of miR-373, down-regulation of CD44 and TGFBR2 by miR-373 are partly responsible for the migration, and invasion suppressive role of miR-373 in U251. PMID- 26858155 TI - Study of energy transfer mechanism from ZnO nanocrystals to Eu(3+) ions. AB - In this work, we investigate the efficient energy transfer occurring between ZnO nanocrystals (ZnO-nc) and europium (Eu(3+)) ions embedded in a SiO2 matrix prepared using the sol-gel technique. We show that a strong red emission was observed at 614 nm when the ZnO-nc were excited using a continuous optical excitation at 325 nm. This emission is due to the radiative (5)D0 -> (7)F2 de excitation of the Eu(3+) ions and has been conclusively shown to be due to the energy transfer from the excited ZnO-nc to the Eu(3+) ions. The photoluminescence excitation spectra are also examined in this work to confirm the energy transfer from ZnO-nc to the Eu(3+) ions. Furthermore, we study various de-excitation processes from the excited ZnO-nc and their contribution to the energy transfer to Eu(3+) ions. We also report the optimum fabrication process for maximum red emission at 614 nm from the samples where we show a strong dependence on the annealing temperature and the Eu(3+) concentration in the sample. The maximum red emission is observed with 12 mol% Eu(3+) annealed at 450 degrees C. This work provides a better understanding of the energy transfer mechanism from ZnO-nc to Eu(3+) ions and is important for applications in photonics, especially for light emitting devices. PMID- 26858154 TI - Inhibited Expression of alpha4beta2 Nicotinic Acetylcholine Receptor in Blood Leukocytes of Chinese Patients with Vascular Dementia and in Blood Leukocytes as Well as the Hippocampus of Brain from Ischemic Rats. AB - Our present aim was to investigate whether changes in the expression of alpha4beta2 nicotinic acetylcholine receptor (nAChR) in patients with vascular dementia (VaD) and ischemic rats are related to cognitive scores. Blood leukocytes for 59 Chinese patients with VaD (diagnosed on the basis of clinical guidelines) and 31 cases as age-matched controls were examined, and the animal model established employing Pulsinelli's four-vessel occlusion. The levels of alpha4 and beta2 subunit mRNA in leukocytes and the hippocampus were analyzed by real-time PCR, and the protein level in the hippocampus by Western blotting. The mini-mental state examination was utilized to characterize the intellectual capacity of the patients with reference to the DSM IV diagnosis and Hachinski Ischemic Scale score, and the Morris Water Maze test to assess the ability of learning and memory of the rats. In patients, the level of alpha4 mRNA, but not beta2, in blood leukocytes was clearly lowered, which was significantly correlated to their clinical cognitive test scores. Smoking exerted no impact on the level of alpha4 mRNA in the present study. In the blood leukocytes and the hippocampus of the brains of the ischemic rats, the levels of both alpha4 and beta2 mRNA were lowered, and the proteins of these subunits in the hippocampus were decreased. The changes of alpha4 and beta2 mRNA in blood leukocytes, and their protein levels in the hippocampus were significantly correlated with impaired learning and memory. These findings indicate that alterations in expression of the alpha4beta2 subtype of nAChR may be involved in the molecular mechanism(s) underlying the cognitive deficit associated with VaD. PMID- 26858156 TI - Current in the Protein Nanowires: Quantum Calculations of the Base States. AB - It is known that synthesis of adenosine triphosphoric acid in mitochondrions may be only completed on the condition of transport of the electron pairs, which were created due to oxidation processes, to mitochondrions. As of today, many efforts were already taken in order to understand those processes that occur in the course of donor-acceptor electron transport between cellular organelles (that is, between various proteins and protein structures). However, the problem concerning the mechanisms of electron transport over these organelles still remains understudied. This paper is dedicated to the investigation of these same issues.It has been shown that regardless of the amino acid inhomogeneity of the primary structure, it is possible to apply a representation of the second quantization in respect of the protein molecule (hereinafter "numbers of filling representation"). Based on this representation, it has been established that the primary structure of the protein molecule is actually a semiconductor nanowire. In addition, at the same time, its conduction band, into which an electron is injected as the result of donor-acceptor processes, consists of five sub-bands. Three of these sub-bands have normal dispersion laws, while the rest two sub bands have abnormal dispersion laws (reverse laws). Test calculation of the current density was made under the conditions of the complete absence of the factors, which may be interpreted as external fields. It has been shown that under such conditions, current density is exactly equal to zero. This is the evidence of correctness of the predictive model of the conductivity band of the primary structure of the protein molecule (protein nanowire). At the same time, it makes it possible to apply the obtained results in respect of the actual situation, where factors, which may be interpreted as external fields, exist. PMID- 26858157 TI - Sol-Gel-Prepared Nanoparticles of Mixed Praseodymium Cobaltites-Ferrites. AB - Two series of nanocrystalline powders of PrCo1 - x Fe x O3 (x = 0.1, 0.3, 0.5, 0.7 and 0.9) of high purity were obtained by sol-gel citrate method at 700 and 800 degrees C. The formation of continuous solid solution with an orthorhombic perovskite structure (sp. group Pbnm) was observed. A peculiarity of the PrCo1 - x Fe x O3 solid solution is the lattice parameter crossovers, which occurred at certain compositions and revealed in the pseudo-tetragonal or pseudo-cubic metric. An average crystallite size of the PrCo1 - x Fe x O3 samples estimated from the analysis of the angular dependence of the X-ray diffraction (XRD) line broadening varies between 30 and 155 nm, depending on the composition and synthesis temperature. PMID- 26858158 TI - Dispersion of Phonon Surface Polaritons in ZnGeP2: Anisotropy and Temperature Impacts. AB - Zinc germanium diphosphide (ZnGeP2) is an attractive and promising functional material for different devices of the nano- and optoelectronics. In this paper, dispersion of phonon surface polaritons (PSPs) in ZnGeP2 has been studied in the 200-500-cm(-1) spectral range at 4 and 300 K. Dispersion of "real" and "virtual" PSPs were calculated for C-axis being normal and parallel to the surface. Anisotropy in ZnGeP2 leads to the different numbers of PSP dispersion branches for different orientations of the sample. The temperature-dependent phonon contributions in the dielectric permittivity shift dispersion of the surface polaritons in ZnGeP2 to the higher wavenumbers at 4 K. We have shown that experimental dispersion of PSP is in agreement with theory. PMID- 26858159 TI - Dilute Magnetic Semiconductor and Half-Metal Behaviors in 3d Transition-Metal Doped Black and Blue Phosphorenes: A First-Principles Study. AB - We present first-principles density-functional calculations for the structural, electronic, and magnetic properties of substitutional 3d transition metal (TM) impurities in two-dimensional black and blue phosphorenes. We find that the magnetic properties of such substitutional impurities can be understood in terms of a simple model based on the Hund's rule. The TM-doped black phosphorenes with Ti, V, Cr, Mn, Fe, and Ni impurities show dilute magnetic semiconductor (DMS) properties while those with Sc and Co impurities show nonmagnetic properties. On the other hand, the TM-doped blue phosphorenes with V, Cr, Mn, and Fe impurities show DMS properties, with Ni impurity showing half-metal properties, whereas Sc- and Co-doped systems show nonmagnetic properties. We identify two different regimes depending on the occupation of the hybridized electronic states of TM and phosphorous atoms: (i) bonding states are completely empty or filled for Sc- and Co-doped black and blue phosphorenes, leading to nonmagnetic; (ii) non-bonding d states are partially occupied for Ti-, V-, Cr-, Mn-, Fe- and Ni-doped black and blue phosphorenes, giving rise to large and localized spin moments. These results provide a new route for the potential applications of dilute magnetic semiconductor and half-metal in spintronic devices by employing black and blue phosphorenes. PACS numbers: 73.22.-f, 75.50.Pp, 75.75. + a. PMID- 26858160 TI - Structure and Strength of Iron-Copper-Carbon Nanotube Nanocomposites. AB - Nanocomposite materials of the Fe-Cu system with/without small addition of carbon nanotubes have been synthesized by mechanochemical activation of elemental Fe and Cu powders in a high-energy planetary ball mill and have been examined by the X ray diffraction method, SEM and the thermopower methods; the tensile strength of the materials obtained has been estimated. The metastable (Fe, Cu) supersaturated solid solution is formed in the Fe-Cu nanocomposites during milling process. The coherent scattering block size of the materials obtained is decreased with increase of milling time. The duration of mechanochemical activation affects the physical properties of nanocomposites studied. Addition of a small amount of nanotubes into Fe-Cu charge results in a significant increase of strength of the Fe-Cu (4:1) + CNT nanocomposite materials (NCMs) obtained. PMID- 26858161 TI - The Magnetorheological Finishing (MRF) of Potassium Dihydrogen Phosphate (KDP) Crystal with Fe3O4 Nanoparticles. AB - The cubic Fe3O4 nanoparticles with sharp horns that display the size distribution between 100 and 200 nm are utilized to substitute the magnetic sensitive medium (carbonyl iron powders, CIPs) and abrasives (CeO2/diamond) simultaneously which are widely employed in conventional magnetorheological finishing fluid. The removal rate of this novel fluid is extremely low compared with the value of conventional one even though the spot of the former is much bigger. This surprising phenomenon is generated due to the small size and low saturation magnetization (M s) of Fe3O4 and corresponding weak shear stress under external magnetic field according to material removal rate model of magnetorheological finishing (MRF). Different from conventional D-shaped finishing spot, the low M s also results in a shuttle-like spot because the magnetic controllability is weak and particles in the fringe of spot are loose. The surface texture as well as figure accuracy and PSD1 (power spectrum density) of potassium dihydrogen phosphate (KDP) is greatly improved after MRF, which clearly prove the feasibility of substituting CIP and abrasive with Fe3O4 in our novel MRF design. PMID- 26858162 TI - A Review on Preparation and Applications of Silver-Containing Nanofibers. AB - Silver-containing nanofibers are of great interest recently because of the dual benefits from silver particles and nanofibers. Silver nanoparticles are extensively used for biomedical applications due to the antibacterial and antiviral properties. In addition, silver nanoparticles can excite resonance effect of light trapping when pairing with dielectric materials, such as polymer. Comparing to the traditional fabrics, polymer nanofibers can provide larger number of reaction sites and higher permeability contributed to their high surface-to-volume ratio and high porosity. By embedding the silver nanoparticles into polymer nanofiber matrix, the composite is promising candidates for biomaterials, photovoltaic materials, and catalysts. This work demonstrates and evaluates the methods employed to synthesize silver nanoparticle-containing nanofibers and their potential applications. PMID- 26858163 TI - Study of aroma formation and transformation during the manufacturing process of Biluochun green tea in Yunnan Province by HS-SPME and GC-MS. AB - BACKGROUND: Biluochun is a typical non-fermented tea and is also famous for its unique aroma in China. Few studies have been performed to evaluate the effect of the manufacturing process on the formation and content of its aroma. RESULTS: The volatile components were extracted at different manufacturing process steps of Biluochun green tea using fully automated headspace solid-phase microextraction (HS-SPME) and further characterised by gas chromatography-mass spectrometry (GC MS). Among 67 volatile components collected, the fractions of linalool oxides, beta-ionone, phenylacetaldehyde, aldehydes, ketones, and nitrogen compounds were increased while alcohols and hydrocarbons declined during the manufacturing process. The aroma compounds decreased the most during the drying steps. CONCLUSION: We identified a number of significantly changed components that can be used as markers and quality control during the producing process of Biluochun. The drying step played a major role in the aroma formation of green tea products and should be the most important step for quality control. (c) 2016 Society of Chemical Industry. PMID- 26858164 TI - Magnetic resonance imaging for prostate cancer radiotherapy. AB - For radiotherapy of prostate cancer, MRI is used increasingly for delineation of the prostate gland. For focal treatment of low-risk prostate cancer or focal dose escalation for intermediate and high-risk cancer, delineation of the tumor is also required. While multi-parametric MRI is well established for detection of tumors and for staging of the disease, delineation of the tumor inside the prostate is not common practice. Guidelines, such as the PI-RADS classification, exist for tumor detection and staging, but no such guidelines are available for tumor delineation. Indeed, interobserver studies show substantial variation in tumor contours. Computer-aided tumor detection and delineation may help improve the robustness of the interpretation of multi-parametric MRI data. Comparing the performance of an earlier developed model for tumor segmentation with expert delineations, we found a significant correlation between tumor probability in a voxel and the number of experts identifying this voxel as tumor. This suggests that the model agrees with 'the wisdom of the crowd', and thus could serve as a reference for individual physicians in their decision making. With multi parametric MRI it becomes feasible to revisit the GTV-CTV concept in radiotherapy of prostate cancer. While detection of index lesions is quite reliable, contouring variability and the low sensitivity to small lesions suggest that the remainder of the prostate should be treated as CTV. Clinical trials that investigate the options for dose differentiation, for example with dose escalation to the visible tumor or dose reduction to the CTV, are therefore warranted. PMID- 26858165 TI - Differences between Men and Women in Time Trends in Lung Cancer Mortality in Spain (1980-2013). AB - INTRODUCTION: The main risk factor for lung cancer is smoking, a habit that varies according to age and sex. The objective of this study was to explore trends in lung cancer mortality by sex and age from 1980 to 2013 in Spain. METHODS: We used lung cancer mortality (International Classification of Diseases code 162 for the 9th edition, and codes C33 and C34 for 10th edition) and population data from the Spanish National Statistics Institute. Crude, truncated, age-adjusted mortality and age-specific mortality rates were assessed through joinpoint regression to estimate the annual percent change (APC). RESULTS: Age adjusted mortality rate significantly increased from 1980 to 1991 among men (APC=3.12%) and significantly decreased between 2001 and 2013 (APC=-1.53%), a similar pattern was observed in age-specific rates. Among women, age-adjusted mortality rate increased from 1989 (APC 1989-1997=1.82%), with the greatest increase observed from 1997 until the end of the study in 2013 (APC=4.41%). CONCLUSIONS: Diverging trends in the prevalence of smoking could explain the increase in the rate of lung cancer-related mortality among Spanish women since the early 1990s. Public health policies should be implemented to reduce tobacco consumption in women and halt the increase in lung cancer mortality. PMID- 26858166 TI - Expression of microRNA-133 inhibits epithelial-mesenchymal transition in lung cancer cells by directly targeting FOXQ1. AB - INTRODUCTION: MicroRNA (miR) was implicated in the tumorigenesis of many types of cancer, but no study was conducted on the exact role of miR-133 in lung cancer. METHODS: We have identified miR-133 as a putative regulator of FOXQ1 expression, and investigated the potential involvement of miR-133 in the migration and invasion of lung cancer cells, as well as the underlying molecular mechanism. RESULTS: MiR-133 directly targeted and down-regulated FOXQ1 expression, which in turn reduced TGF-beta level. MiR-133 was down-regulated in lung cancer cell lines A549 and HCC827, and its re-expression significantly inhibited the migration and invasion of the lung cancer cells. Further investigation revealed that this inhibition was caused by reversing the epithelial-mesenchymal transition, evidenced by miR-133 induced elevation of epithelial marker E-cadherin, and reduction of mesenchymal marker Vimentin. CONCLUSIONS: Our study is the first to identify miR-133 as a biomarker for lung cancer. It functions to down-regulate FOXQ1, and inhibit epithelial-mesenchymal transition, which antagonizes lung cancer tumorigenesis. Therefore our data support the role of miR-133 as a potential molecular therapeutic tool in treating lung cancer. PMID- 26858167 TI - Development of MEPS-UHPLC-MS/MS multistatin methods for clinical analysis. AB - BACKGROUND: Statins are the microsomal 3-hydroxy-3methylglutaryl-coenzyme A reductase inhibitors used for the treatment of hypercholesterolemia. Some recent studies revealed also the extra-lipid effects and anticancer activities. Due to the wide incidence of cancer diseases, the number of studies dealing with anticancer statin activities has grown in recent years. Development of one universal multistatin method will be a very convenient way of providing practical and economical multiple statin analysis. Results/methodology: Fast and sensitive methods for determination of seven clinically relevant statins, their interconversion products and metabolites (17 analytes in total) in biological samples using microextraction by packed sorbent for sample preparation and UHPLC MS/MS for subsequent analysis were developed and validated. Three MS platforms with different ion sources, transfer optics, collision cell technologies and scan speed parameters were compared. CONCLUSION: Significant differences among the methods were observed in terms of selectivity and sensitivity. Microextraction by packed sorbent was successful in the extraction of all 17 analytes from biological matrix. PMID- 26858168 TI - Real-time in vitro intravascular reconstruction and navigation for endovascular aortic stent grafting. AB - BACKGROUND: Trans-catheter endovascular stent grafting minimizes trauma and increases the benefitting patient population. However, the alignment between stent graft branches and vasculature branches remains time-consuming and challenging, and such techniques require a significant amount of contrast agent for imaging. METHODS: A new framework for intravascular reconstruction based on sensor fusion between intravascular ultrasound (IVUS) imaging and electromagnetic (EM) tracking was proposed. A new image processing method was presented to realize fully automatic processing of IVUS imaging and 3D reconstruction in real time, as well as branch detection for alignment and deployment. Complementary navigation using CT data allows for efficient catheter advancement and assistant clinical judgement. RESULTS: The reconstruction of an in vitro descending aorta phantom with branches was realized at 35 Hz, with cross-section radius average error of 0.64 mm. CONCLUSION: The proposed method demonstrates significant potential for clinical applications, enables navigation for precise alignment and placement for stent grafting to reduce surgical time, and decreases hemorrhagic collisions and the use of contrast agent. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26858169 TI - Advancing supplement science: challenges and solutions. PMID- 26858170 TI - Reiki Therapy for Symptom Management in Children Receiving Palliative Care: A Pilot Study. AB - BACKGROUND: Pain may be reported in one-half to three-fourths of children with cancer and other terminal conditions and anxiety in about one-third of them. Pharmacologic methods do not always give satisfactory symptom relief. Complementary therapies such as Reiki may help children manage symptoms. OBJECTIVE: This pre-post mixed-methods single group pilot study examined feasibility, acceptability, and the outcomes of pain, anxiety, and relaxation using Reiki therapy with children receiving palliative care. METHODS: A convenience sample of children ages 7 to 16 and their parents were recruited from a palliative care service. Two 24-minute Reiki sessions were completed at the children's home. Paired t tests or Wilcoxon signed-rank tests were calculated to compare change from pre to post for outcome variables. Significance was set at P < .10. Cohen d effect sizes were calculated. RESULTS: The final sample included 8 verbal and 8 nonverbal children, 16 mothers, and 1 nurse. All mean scores for outcome variables decreased from pre- to posttreatment for both sessions. Significant decreases for pain for treatment 1 in nonverbal children ( P = .063) and for respiratory rate for treatment 2 in verbal children ( P = .009). Cohen d effect sizes were medium to large for most outcome measures. DISCUSSION: Decreased mean scores for outcome measures indicate that Reiki therapy did decrease pain, anxiety, heart, and respiratory rates, but small sample size deterred statistical significance. This preliminary work suggests that complementary methods of treatment such as Reiki may be beneficial to support traditional methods to manage pain and anxiety in children receiving palliative care. PMID- 26858171 TI - Spirituality and Awareness of Diagnoses in Terminally Ill Patients With Cancer. AB - OBJECTIVE: Aims of the present study were to investigate the association between awareness of own illness condition and psychological outcome in end-of-life phase and to test the association between the spirituality and the awareness of own illness condition. METHODS: Three hundred and ninety-nine terminally ill patients with cancer were enrolled in a hospice in central Italy. One hundred patients satisfied the inclusion criteria. The Systems of Belief Inventory, the Hospital Anxiety and Depression Scale, and a psychological interview to determine the level of awareness of the illness diagnosis (aware; partially aware; and not aware) were administered to terminally ill patients. RESULTS: The main finding was that the awareness of one's own illness condition was positively associated with the extrinsic spirituality and negatively associated with intrinsic spirituality (regression model R = .26; R2 = .07; adjusted R2 = .05; F2, 97 = 3.45; P = .036). The aware group showed lower anxiety and depression ( F2, 97 = 1.9; P = . 075; F2, 97 = 2.6; P = .04) scores than partially aware and not aware groups. The psychological outcome was not associated with the spirituality level. CONCLUSION: In terminally ill patients with cancer, the levels of depression and anxiety were lower in patients aware of their own illness state. Moreover, higher levels of extrinsic and lower levels of intrinsic spirituality predicted the awareness of one's own illness state. PMID- 26858172 TI - What's new in the diagnostic criteria of disseminated intravascular coagulation? PMID- 26858173 TI - The Experience in Personal Social Systems Questionnaire (EXIS.pers): Development and Psychometric Properties. AB - This study presents the theoretical background, development, and psychometric properties of the German and English versions of the Experience in Personal Social Systems Questionnaire (EXIS.pers). It assesses how the members of a personal social system experience their situation within that system. It is designed as a research tool for interventions in which only one member of the system participates (e.g., Family Constellation Seminars). The EXIS.pers was created to measure change on the individual level relating to one's own important personal social system. In Study 1, we used exploratory factor analysis (EFA) for latent variable identification of the original German EXIS.pers (n = 179). In Studies 2 and 3, we used confirmatory factor analysis (CFA) to examine the dimensionality of the German (n = 634) and English (n = 310) EXIS.pers. Internal consistencies and cross-cultural structural equivalence were assessed. EFA indicated that a four-factor model provided best fit for the German EXIS.pers. For both the German and English EXIS.pers, CFA provided the best fit for a five factor bi-level model that included a general factor (Experience In Personal Social Systems) and four dimensions (Belonging, Autonomy, Accord, Confidence). Good internal consistencies, external associations, and cross-cultural structural equivalence were demonstrated. This study provides first evidence for the German and English EXIS.pers as an economical and reliable measure of an individual's experience within his or her personal social systems. PMID- 26858174 TI - Antithrombin III for critically ill patients. AB - BACKGROUND: Critical illness is associated with uncontrolled inflammation and vascular damage which can result in multiple organ failure and death. Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties but the efficacy and any harmful effects of AT III supplementation in critically ill patients are unknown. This review was published in 2008 and updated in 2015. OBJECTIVES: To examine:1. The effect of AT III on mortality in critically ill participants.2. The benefits and harms of AT III.We investigated complications specific and not specific to the trial intervention, bleeding events, the effect on sepsis and disseminated intravascular coagulation (DIC) and the length of stay in the intensive care unit (ICU) and in hospital in general. SEARCH METHODS: We searched the following databases from inception to 27 August 2015: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid SP), EMBASE (Ovid SP,), CAB, BIOSIS and CINAHL. We contacted the main authors of trials to ask for any missed, unreported or ongoing trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published, or language. We contacted the investigators and the trial authors in order to retrieve missing data. In this updated review we include trials only published as abstracts. DATA COLLECTION AND ANALYSIS: Our primary outcome measure was mortality. Two authors each independently abstracted data and resolved any disagreements by discussion. We presented pooled estimates of the intervention effects on dichotomous outcomes as risk ratios (RR) with 95% confidence intervals (CI). We performed subgroup analyses to assess risk of bias, the effect of AT III in different populations (sepsis, trauma, obstetrics, and paediatrics), and the effect of AT III in patients with or without the use of concomitant heparin. We assessed the adequacy of the available number of participants and performed trial sequential analysis (TSA) to establish the implications for further research. MAIN RESULTS: We included 30 RCTs with a total of 3933 participants (3882 in the primary outcome analyses).Combining all trials, regardless of bias, showed no statistically significant effect of AT III on mortality with a RR of 0.95 (95% CI 0.88 to 1.03), I2 statistic = 0%, fixed-effect model, 29 trials, 3882 participants, moderate quality of evidence). For trials with low risk of bias the RR was 0.96 (95% Cl 0.88 to 1.04, I2 statistic = 0%, fixed-effect model, 9 trials, 2915 participants) and for high risk of bias RR 0.94 (95% Cl 0.77 to 1.14, I2 statistic = 0%, fixed-effect model, 20 trials, 967 participants).For participants with severe sepsis and DIC the RR for mortality was non-significant, 0.95 (95% Cl 0.88 to 1.03, I2 statistic = 0%, fixed-effect model, 12 trials, 2858 participants, moderate quality of evidence).We conducted 14 subgroup and sensitivity analyses with respect to the different domains of risk of bias, but detected no statistically significant benefit in any subgroup analyses.Our secondary objective was to assess the benefits and harms of AT III. For complications specific to the trial intervention the RR was 1.26 (95% Cl 0.83 to 1.92, I2 statistic = 0%, random-effect model, 3 trials, 2454 participants, very low quality of evidence). For complications not specific to the trial intervention, the RR was 0.71 (95% Cl 0.08 to 6.11, I2 statistic = 28%, random effects model, 2 trials, 65 participants, very low quality of evidence). For complications other than bleeding, the RR was 0.72 ( 95% Cl 0.42 to 1.25, I2 statistic = 0%, fixed-effect model, 3 trials, 187 participants, very low quality of evidence). Eleven trials investigated bleeding events and we found a statistically significant increase, RR 1.58 (95% CI 1.35 to 1.84, I2 statistic = 0%, fixed-effect model, 11 trials, 3019 participants, moderate quality of evidence) in the AT III group. The amount of red blood cells administered had a mean difference (MD) of 138.49 (95% Cl -391.35 to 668.34, I2 statistic = 84%, random-effect model, 4 trials, 137 participants, very low quality of evidence). The effect of AT III in patients with multiple organ failure (MOF) was a MD of 1.24 (95% Cl -2.18 to -0.29, I2 statistic = 48%, random-effects model, 3 trials, 156 participants, very low quality of evidence) and for patients with an Acute Physiology and Chronic Health Evaluation score (APACHE) at II and III the MD was 2.18 (95% Cl -4.36 to -0.00, I2 statistic = 0%, fixed-effect model, 3 trials, 102 participants, very low quality of evidence). The incidence of respiratory failure had a RR of 0.93 (95% Cl 0.76 to 1.14, I2 statistic = 32%, random-effects model, 6 trials, 2591 participants, moderate quality of evidence). AT III had no statistically significant impact on the duration of mechanical ventilation (MD 2.20 days, 95% Cl -1.21 to 5.60, I2 statistic = 0%, fixed-effect model, 3 trials, 190 participants, very low quality of evidence); on the length of stay in the ICU (MD 0.24, 95% Cl -1.34 to 1.83, I2 statistic = 0%, fixed-effect model, 7 trials, 376 participants, very low quality of evidence) or on the length of stay in hospital in general (MD 1.10, 95% Cl -7.16 to 9.36), I2 statistic = 74%, 4 trials, 202 participants, very low quality of evidence). AUTHORS' CONCLUSIONS: There is insufficient evidence to support AT III substitution in any category of critically ill participants including the subset of patients with sepsis and DIC. We did not find a statistically significant effect of AT III on mortality, but AT III increased the risk of bleeding events. Subgroup analyses performed according to duration of intervention, length of follow-up, different patient groups, and use of adjuvant heparin did not show differences in the estimates of intervention effects. The majority of included trials were at high risk of bias (GRADE; very low quality of evidence for most of the analyses). Hence a large RCT of AT III is needed, without adjuvant heparin among critically ill patients such as those with severe sepsis and DIC, with prespecified inclusion criteria and good bias protection. PMID- 26858175 TI - NICE recommends pulmonary rehabilitation programmes for patients with COPD. PMID- 26858176 TI - What happens in vagus: a case of recurrent paraganglioma with malignant transformation and an updated treatment algorithm?. AB - Paragangliomas (PGLs) are rare, extra-adrenal tumors, originating from neural crest cells and can occur anywhere from the skull base to the pelvic floor. Although these tumors are often benign, a fraction of malignant cases exist. Few isolated cases of malignant head and neck PGL are reported in the literature. Treatment algorithms rely heavily on retrospective case studies and institutional experience. We report an unusual case of an extensive, hereditary PGL, with invasive characteristics, that was refractory to radiation therapy. An operative approach was selected for recurrent disease in the setting of critical neurovascular structure compromise. Six months postoperatively, the patient was recovering as expected and had no evidence of recurrent disease. We propose a modified treatment algorithm based on an updated literature review that encompasses the spectrum of PGL, from benign and asymptomatic to invasive and malignant disease. PMID- 26858177 TI - Neuroprotection Promoted by Guanosine Depends on Glutamine Synthetase and Glutamate Transporters Activity in Hippocampal Slices Subjected to Oxygen/Glucose Deprivation. AB - Guanosine (GUO) has been shown to act as a neuroprotective agent against glutamatergic excitotoxicity by increasing glutamate uptake and decreasing its release. In this study, a putative effect of GUO action on glutamate transporters activity modulation was assessed in hippocampal slices subjected to oxygen and glucose deprivation (OGD), an in vitro model of brain ischemia. Slices subjected to OGD showed increased excitatory amino acids release (measured by D [(3)H]aspartate release) that was prevented in the presence of GUO (100 uM). The glutamate transporter blockers, DL-TBOA (10 uM), DHK (100 uM, selective inhibitor of GLT-1), and sulfasalazine (SAS, 250 uM, Xc(-) system inhibitor) decreased OGD induced D-aspartate release. Interestingly, DHK or DL-TBOA blocked the decrease in glutamate release induced by GUO, whereas SAS did not modify the GUO effect. GUO protected hippocampal slices from cellular damage by modulation of glutamate transporters, however selective blockade of GLT-1 or Xc- system only did not affect this protective action of GUO. OGD decreased hippocampal glutamine synthetase (GS) activity and GUO recovered GS activity to control levels without altering the kinetic parameters of GS activity, thus suggesting GUO does not directly interact with GS. Additionally, the pharmacological inhibition of GS activity with methionine sulfoximine abolished the effect of GUO in reducing D aspartate release and cellular damage evoked by OGD. Altogether, results in hippocampal slices subjected to OGD show that GUO counteracts the release of excitatory amino acids, stimulates the activity of GS, and decreases the cellular damage by modulation of glutamate transporters activity. PMID- 26858179 TI - Technical Assistance to Enhance Prevention Capacity: a Research Synthesis of the Evidence Base. AB - Despite the availability of many evidence-based prevention interventions (EBIs), gaps exist in bringing these programs into widespread practice. Technical assistance (TA) is a strategy for enhancing the readiness of practitioners to implement EBIs. Although many millions of dollars are spent on TA each year, there is little consensus about what the essential features of TA are and how to provide TA with quality. A broad-based research synthesis methodology was used for analyzing the current evidence base for TA using three frames: (1) applying the Getting To Outcomes (GTO) model for categorizing evidence on TA that specifies tasks for planning, implementing, and evaluating TA; (2) understanding the relevance of a successful relationship between the TA provider and TA recipient; and (3) considering the extent to which TA fits the life cycle needs of the preventive intervention. Results indicated that an explicit model or organizing framework is rarely used to plan, implement, and/or evaluate TA; specific TA tasks performed vary widely across studies; TA is rarely delivered to recipients who are seeking to sustain innovations subsequent to adoption and implementation; however, there is systematic attention to relationships and relationship-building. Overall, this synthesis indicates that the extent to which TA is being delivered systematically is limited. We suggest that funders and other stakeholders develop and implement standards for TA quality in order to ensure that many of these limitations are addressed. PMID- 26858180 TI - Seize the Day to Implement Depression Guidelines. PMID- 26858178 TI - Combined Effects of Simultaneous Exposure to Caffeine and Cocaine in the Mouse Striatum. AB - Caffeine is the world's most popular psychoactive drug and is also an active adulterant found in many drugs of abuse, including seized cocaine samples. Despite several studies which examine the effects of caffeine or cocaine administered as single agents, little data are available for these agents when given in combination. The purpose of the present study was to determine if combined intake of both psychostimulants can lead to maladaptive changes in striatal function. Mice were injected with a binge regimen (intermittent treatment for 13 days) of caffeine (3 * 5 mg/kg), cocaine (3 * 10 mg/kg), or combined administration. We found that chronic caffeine potentiated locomotion induced by cocaine and that both caffeine-treated groups showed sensitization. Striatal tissue was obtained 24 h and 7 days after last injection (withdrawal) for immunohistochemistry and mRNA expression. Our results show that combined intake of both psychostimulants can increase GFAP immunoreactivity in the striatum at both times post treatment. Gene expression analysis, targeted at dopamine, adenosine, and glutamate receptor subunit genes, revealed significant transcript down-regulation in the dorsal striatum of AMPA, NMDA, D1 and D2 receptor subunit mRNA expression in the group that received combined treatment, but not after individual administration. At withdrawal, we found increased D1 receptor mRNA expression along with increased A1, AMPA, NMDA, and metabotropic subunit expression. A2A mRNA showed decreased expression after both times in all experimental groups. Our study provides evidence that there are striatal alterations mediated by combined caffeine and cocaine administration, and highlights negative outcomes of chronic intake of both psychostimulants. PMID- 26858182 TI - Lower extremity ulcers. PMID- 26858181 TI - Identification of HDAC Inhibitors Using a Cell-Based HDAC I/II Assay. AB - Histone deacetylases (HDACs) are a class of epigenetic enzymes that regulate gene expression by histone deacetylation. Altered HDAC function has been linked to cancer and neurodegenerative diseases, making HDACs popular therapeutic targets. In this study, we describe a screening approach for identification of compounds that inhibit endogenous class I and II HDACs. A homogeneous, luminogenic HDAC I/II assay was optimized in a 1536-well plate format in several human cancer cell lines, including HCT116 and human neural stem cells. The assay confirmed 37 known HDAC inhibitors from two libraries of known epigenetics-active compounds. Using the assay, we identified a group of potential HDAC inhibitors by screening the National Center for Advancing Translational Sciences (NCATS) Pharmaceutical Collection of 2527 small-molecule drugs. The selected compounds showed similar HDAC I/II inhibitory potency and efficacy values in both HCT116 and neural stem cells. Several previously unidentified HDAC inhibitors were further evaluated and profiled for their selectivity against a panel of 10 HDAC I/II isoforms using fluorogenic HDAC biochemical assays. In summary, our results show that several novel HDAC inhibitors, including nafamostat and piceatannol, have been identified using the HDAC I/II cell-based assay, and multiple cell types have been validated for high-throughput screening of large chemical libraries. PMID- 26858183 TI - Malperfusion syndromes in aortic dissections. AB - Aortic dissection remains a challenging clinical scenario, especially when complicated by peripheral malperfusion. Improvements in medical imaging have furthered understanding of the pathophysiology of malperfusion events in association with aortic dissection, including the elucidation of different mechanisms of branch vessel obstruction. Despite these advances, malperfusion syndrome remains a deadly entity with significant mortality. This review presents the latest knowledge regarding the pathogenesis of aortic dissection complicated by malperfusion syndrome, and discusses the diagnostic and therapeutic guidelines for management of this vicious entity. PMID- 26858185 TI - Abdominal aortic aneurysm and histological, clinical, radiological correlation. AB - To date, the pathogenesis of abdominal aortic aneurism (AAA) still remains unclear. As such, the aim of this study was to evaluate changes of the aortic structure during AAA. We analysed the microscopic frame of vessels sections, starting from the primum movens leading to abnormal dilatation. AAA samples were collected and processed through various staining methods (Verhoeff-Van Gieson, Masson Goldner, Sirius Red). Subsequently, the vessel morphology and collagenic web of the tunica media and adventitia were determined and the amount of type I and type III collagen was measured. We also applied immune-histochemistry markers for CD34 and PGP 9.5 in order to identify vascular and nerve structures in the aorta. Immune-positivity quantification was used to calculate the percentage of the stained area. We found increasing deposition of type I collagen and reduced type III collagen in both tunica media and adventitia of AAA. The total amount of vasa vasorum, marked with CD34, and nerva vasorum, marked with PGP 9.5, was also higher in AAA samples. Cardiovascular risk factors (blood pressure, dyslipidemia, cigarette smoking) and radiological data (maximum aneurism diameter, intra luminal thrombus, aortic wall calcification) increased these changes. These results suggest that the tunica adventitia may have a central role in the pathogenesis of AAA as clearly there are major changes characterized by rooted inflammatory infiltration. The presence of immune components could explain these modifications within the framework of the aorta. PMID- 26858184 TI - Minimally invasive follicular thyroid carcinomas: prognostic factors. AB - Although minimally invasive follicular thyroid carcinoma (MI-FTC) is regarded as an indolent tumour, treatment strategies remain controversial. Our aim was to investigate the outcome for patients with MI-FTC and to identify prognostic parameters to facilitate adequate treatment and follow-up. This retrospective follow-up study involved all cases of MI-FTC operated at the Karolinska University Hospital between 1986 and 2009. Outcome was analysed using death from MI-FTC as endpoint. Fifty-eight patients (41 women and 17 men) with MI-FTC were identified. The median follow-up time was 140 (range 21-308) months. Vascular invasion was observed in 36 cases and was associated with larger tumour size [median 40 (20-76) compared with 24 (10-80) mm for patients with capsular invasion only (P = 0.001)] and older patients [54 (20-92) vs. 44 (11-77) years; P = 0.019]. Patients with vascular invasion were more often treated with thyroidectomy (21/36 compared to 7/22 with capsular invasion only; P = 0.045). Five patients died from metastatic disease of FTC after a median follow-up of 114 (range 41-193) months; all were older than 50 years (51-72) at the time of the initial surgery; vascular invasion was present in all tumours and all but one were treated with thyroidectomy. Univariate analysis identified combined capsular and vascular invasion (P = 0.034), age at surgery >=50 years (P = 0.023) and male gender (P = 0.005) as related to risk of death from MI-FTC. MI-FTC should not be considered a purely indolent disease. Age at diagnosis and the existence of combined capsular and vascular invasion were identified as important prognostic factors. PMID- 26858186 TI - Retinoic acid decreases the severity of Salmonella enterica serovar Typhimurium mediated gastroenteritis in a mouse model. AB - Gastroenteritis is a global burden; it's the major cause of morbidity and mortality both in adults and children of developing countries. Salmonella is one of the leading causes of bacteria-mediated gastroenteritis and due to its increasing multidrug antibiotic resistance; Salmonella-mediated gastroenteritis is difficult to control. Retinoic acid, the biologically active agent of vitamin A has an anti-inflammatory effect on experimental colitis. In this study we have shown All trans retinoic acid (ATRA) treatment down regulates Salmonella-mediated colitis in a murine model. Macroscopic signs of inflammation such as decrease in body weight and cecum weight, shorter length of proximal colon and pathological score of colitis were observed less in ATRA treated mice than in a vehicle control group. ATRA treatment not only reduced pro-inflammatory cytokine responses, such as TNF-alpha, IL-6, IL-1beta, IFN-gamma and IL-17 production but also increased IL-10 response in the supernatant of intestinal tissue. Results also suggested that ATRA treatment enhances the number of FoxP3-expressing T regulatory cells in MLN and also decreases bacterial load in systemic organs. We concluded that ATRA treatment indeed reduces Salmonella Typhimurium-mediated gastroenteritis in mice, suggesting it could be an important part of an alternative therapeutic approach to combat the disease. PMID- 26858188 TI - Reply. PMID- 26858189 TI - Asthma Action Plan Receipt among Children with Asthma 2-17 Years of Age, United States, 2002-2013. AB - OBJECTIVE: To examine national trends in the receipt of asthma action plans, an intervention recommended by the National Asthma Education and Prevention Program guidelines. STUDY DESIGN: We used data from the sample child component of the National Health Interview Survey from 2002, 2003, 2008, and 2013 to examine the percentage of children 2-17 years of age with asthma (n = 3714) that have ever received an asthma action plan. Bivariate and multivariate (with adjustment for sociodemographic characteristics and asthma outcomes consistent with greater disease severity) logistic regressions were conducted to examine trends from 2002 to 2013 and to examine, with 2013 data only, the relationship between having received an asthma action plan and both sociodemographic characteristics and indicators of asthma severity. RESULTS: The percentage of children with asthma that had ever received an asthma action plan increased from 41.7% in 2002 to 50.7% in 2013 (P < .001 for trend). In 2013, a greater percentage of non-Hispanic black (58.4%) than non-Hispanic white (47.4%) children (P = .028), privately insured (56.2%) vs those with public insurance only (46.3%) (P = .016), and users of inhaled preventive asthma medication vs those that did not (P < .001) had ever received an asthma action plan. Adjusted results were similar. CONCLUSION: The percentage of US children with asthma that had ever received an asthma action plan increased between 2002 and 2013, although one-half had never received an asthma action plan in 2013. Some sociodemographic and asthma severity measures are related to receipt of an asthma action plan. PMID- 26858187 TI - Molecular Genetic Dissection and Neonatal/Infantile Intrahepatic Cholestasis Using Targeted Next-Generation Sequencing. AB - OBJECTIVES: To ascertain a molecular genetic diagnosis for subjects with neonatal/infantile intrahepatic cholestasis (NIIC) by the use of next-generation sequencing (NGS) and to perform a genotype-phenotype correlation. STUDY DESIGN: We recruited Japanese subjects with NIIC who had no definitive molecular genetic diagnosis. We developed a diagnostic custom panel of 18 genes, and the amplicon library was sequenced via NGS. We then compared clinical data between the molecular genetically confirmed subjects with NIIC. RESULTS: We analyzed 109 patients with NIIC ("genetic cholestasis," 31 subjects; "unknown with complications" such as prematurity, 46 subjects; "unknown without complications," 32 subjects), and a molecular genetic diagnosis was made for 28 subjects (26%). The rate of positive molecular genetic diagnosis in each category was 22 of 31 (71%) for the "genetic cholestasis" group, 2 of 46 (4.3%) for the "unknown with complications" group, and 4 of 32 (12.5%) for the "unknown without complications" group. The grouping of the molecular diagnoses in the group with genetic cholestasis was as follows: 12 with Alagille syndrome, 5 with neonatal Dubin Johnson syndrome, 5 with neonatal intrahepatic cholestasis caused by citrin deficiency, and 6 with progressive familial intrahepatic cholestasis or benign recurrent intrahepatic cholestasis with low gamma-glutamyl transpeptidase levels. Several clinical datasets, including age of onset, direct bilirubin, and aminotransferases, were significantly different between the disorders confirmed using molecular genetic diagnosis. CONCLUSION: Targeted NGS can be used for molecular genetic diagnosis in subjects with NIIC. Clinical diagnosis should be accordingly redefined in the view of molecular genetic findings. PMID- 26858190 TI - Abdominal Pain and Chest Wall Deformity in a Teen Athlete. PMID- 26858191 TI - Juvenile Idiopathic Arthritis with Rice Bodies in a 2-Year-Old Girl. PMID- 26858192 TI - Hearing in Children with Congenital Cytomegalovirus Infection: Results of a Longitudinal Study. AB - OBJECTIVES: To evaluate hearing outcome, to characterize the nature of symptomatic and asymptomatic congenital cytomegalovirus (cCMV) infection and associated hearing loss, and to compare results with data from previous studies. STUDY DESIGN: A prospective multicenter registry was set up in 2007. Six centers participated in the development of a standardized protocol for diagnosis, treatment, and follow-up. Data were gathered in an online registry. Children (n = 379) with a documented cCMV infection and at least 2 separate audiologic evaluations were included. Audiometric results from a multicenter cohort study of children with cCMV infection with longitudinal observation were examined. RESULTS: Results from 123 children with a symptomatic and 256 children with an asymptomatic cCMV infection were analyzed. In the group with symptomatic cCMV, 63% had hearing loss, compared with 8% in the group with asymptomatic cCMV. Delayed-onset hearing loss occurred in 10.6% of symptomatic cCMV and in 7.8% of asymptomatic cCMV. In the group with symptomatic cCMV, 29.3% of children used some kind of hearing amplification; 1.6% in the group with asymptomatic cCMV used hearing amplification. CONCLUSIONS: Symptomatic and asymptomatic cCMV infections are a major cause of hearing loss in childhood. Reliable estimates of the long term outcome of cCMV infection are mandatory to increase vigilance, especially among pregnant women and to draw attention to preventive measures, vaccine development, and prenatal and postnatal therapy. Universal screening of newborns for cCMV infection should be initiated and combined with longitudinal audiometric follow-up. PMID- 26858193 TI - Safety of Everolimus in Patients Younger than 3 Years of Age: Results from EXIST 1, a Randomized, Controlled Clinical Trial. AB - OBJECTIVES: To assess the long-term safety of everolimus in young children with tuberous sclerosis complex (TSC)-associated subependymal giant cell astrocytoma (SEGA). STUDY DESIGN: EXamining everolimus In a Study of Tuberous Sclerosis Complex-1 (EXIST-1) was a multicenter, randomized, double-blind phase 3 study with an open-label extension evaluating the efficacy and tolerability of everolimus in patients with TSC-associated SEGA. Everolimus was initiated at 4.5 mg/m(2)/day and titrated to blood trough levels of 5-15 ng/mL. Post hoc analysis of safety data (adverse events [AEs]) was performed in a subgroup of patients aged <3 years at everolimus initiation. RESULTS: Eighteen patients (median age 1.82 years) were included; 16 were still receiving everolimus at the analysis cut off date of January 11, 2013. Median everolimus exposure was 31.1 months (range, 11.5-39 months). One patient discontinued treatment because of AEs (ie, Acinetobacter bacteremia, increased blood alkaline phosphatase, and viral infection). AEs were reported in all patients, but events were mostly grade 1/2 in severity; 12 patients (66.7%) experienced grade 3 events, and 2 patients (11.1%) reported grade 4 events. The most common AEs were stomatitis, cough, pharyngitis, and pyrexia; no new safety issues were identified in this population. Serious AEs were reported in 50% of patients; these were suspected to be medication related in 4 patients (22.2%). CONCLUSIONS: Everolimus appears to be a safe therapeutic option for patients aged <3 years with TSC-associated SEGA. The small sample size in this subpopulation limits interpretation of the results; additional studies in the pediatric population are needed and are underway. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00789828. PMID- 26858194 TI - Risk Factors for Child Malnutrition in Bangladesh: A Multilevel Analysis of a Nationwide Population-Based Survey. AB - OBJECTIVE: To identify the prevalence and risk factors of child malnutrition in Bangladesh. STUDY DESIGN: Data was extracted from the Bangladesh Demographic Health Survey (2011). The outcome measures were stunting, wasting, and underweight. chi(2) analysis was performed to find the association of outcome variables with selected factors. Multilevel logistic regression models with a random intercept at each of the household and community levels were used to identify the risk factors of stunting, wasting, and underweight. RESULTS: From the 2011 survey, 7568 children less than 5 years of age were included in the current analysis. The overall prevalence of stunting, wasting, and underweight was 41.3% (95% CI 39.0-42.9). The chi(2) test and multilevel logistic regression analysis showed that the variables age, sex, mother's body mass index, mother's educational status, father's educational status, place of residence, socioeconomic status, community status, religion, region of residence, and food security are significant factors of child malnutrition. Children with poor socioeconomic and community status were at higher risk of malnutrition. Children from food insecure families were more likely to be malnourished. Significant community- and household-level variations were found. CONCLUSIONS: The prevalence of child malnutrition is still high in Bangladesh, and the risk was assessed at several multilevel factors. Therefore, prevention of malnutrition should be given top priority as a major public health intervention. PMID- 26858195 TI - Amino Acid Metabolism is Altered in Adolescents with Nonalcoholic Fatty Liver Disease-An Untargeted, High Resolution Metabolomics Study. AB - OBJECTIVE: To conduct an untargeted, high resolution exploration of metabolic pathways that was altered in association with hepatic steatosis in adolescents. STUDY DESIGN: This prospective, case-control study included 39 Hispanic-American, obese adolescents aged 11-17 years evaluated for hepatic steatosis using magnetic resonance spectroscopy. Of these 39 individuals, 30 had hepatic steatosis >=5% and 9 were matched controls with hepatic steatosis <5%. Fasting plasma samples were analyzed in triplicate using ultra-high resolution metabolomics on a Thermo Fisher Q Exactive mass spectrometry system, coupled with C18 reverse phase liquid chromatography. Differences in plasma metabolites between adolescents with and without nonalcoholic fatty liver disease (NAFLD) were determined by independent t tests and visualized using Manhattan plots. Untargeted pathway analyses using Mummichog were performed among the significant metabolites to identify pathways that were most dysregulated in NAFLD. RESULTS: The metabolomics analysis yielded 9583 metabolites, and 7711 with 80% presence across all samples remained for statistical testing. Of these, 478 metabolites were associated with the presence of NAFLD compared with the matched controls. Pathway analysis revealed that along with lipid metabolism, several major amino acid pathways were dysregulated in NAFLD, with tyrosine metabolism being the most affected. CONCLUSIONS: Metabolic pathways of several amino acids are significantly disturbed in adolescents with elevated hepatic steatosis. This is a novel finding and suggests that these pathways may be integral in the mechanisms of NAFLD. PMID- 26858196 TI - Metal-Dependent Function of a Mammalian Acireductone Dioxygenase. AB - The two acireductone dioxygenase (ARD) isozymes from the methionine salvage pathway of Klebsiella oxytoca are the only known pair of naturally occurring metalloenzymes with distinct chemical and physical properties determined solely by the identity of the divalent transition metal ion (Fe(2+) or Ni(2+)) in the active site. We now show that this dual chemistry can also occur in mammals. ARD from Mus musculus (MmARD) was studied to relate the metal ion identity and three dimensional structure to enzyme function. The iron-containing isozyme catalyzes the cleavage of 1,2-dihydroxy-3-keto-5-(thiomethyl)pent-1-ene (acireductone) by O2 to formate and the ketoacid precursor of methionine, which is the penultimate step in methionine salvage. The nickel-bound form of ARD catalyzes an off-pathway reaction resulting in formate, carbon monoxide (CO), and 3-(thiomethyl) propionate. Recombinant MmARD was expressed and purified to obtain a homogeneous enzyme with a single transition metal ion bound. The Fe(2+)-bound protein, which shows about 10-fold higher activity than that of others, catalyzes on-pathway chemistry, whereas the Ni(2+), Co(2+), or Mn(2+) forms exhibit off-pathway chemistry, as has been seen with ARD from Klebsiella. Thermal stability of the isozymes is strongly affected by the metal ion identity, with Ni(2+)-bound MmARD being the most stable, followed by Co(2+) and Fe(2+), and Mn(2+)-bound ARD being the least stable. Ni(2+)- and Co(2+)-bound MmARD were crystallized, and the structures of the two proteins found to be similar. Enzyme-ligand complexes provide insight into substrate binding, metal coordination, and the catalytic mechanism. PMID- 26858197 TI - Cyanobacteria use micro-optics to sense light direction. AB - Bacterial phototaxis was first recognized over a century ago, but the method by which such small cells can sense the direction of illumination has remained puzzling. The unicellular cyanobacterium Synechocystis sp. PCC 6803 moves with Type IV pili and measures light intensity and color with a range of photoreceptors. Here, we show that individual Synechocystis cells do not respond to a spatiotemporal gradient in light intensity, but rather they directly and accurately sense the position of a light source. We show that directional light sensing is possible because Synechocystis cells act as spherical microlenses, allowing the cell to see a light source and move towards it. A high-resolution image of the light source is focused on the edge of the cell opposite to the source, triggering movement away from the focused spot. Spherical cyanobacteria are probably the world's smallest and oldest example of a camera eye. PMID- 26858198 TI - Induction chemotherapy-based larynx preservation program for locally advanced hypopharyngeal cancer: oncologic and functional outcomes and prognostic factors. AB - To evaluate oncologic and functional outcomes and prognostic factors in patients with locally advanced hypopharyngeal cancer included in an induction chemotherapy (ICT)-based larynx preservation program in daily clinical practice. All patients with locally advanced (T3/4, N0-3, M0) hypopharyngeal squamous cell carcinoma, technically suitable for total pharyngo-laryngectomy, treated by docetaxel (75 mg/m(2), day 1), cisplatin (75 mg/m(2), day 1) and 5-fluorouracil (750 mg/m(2)/day, day 1-5) (TPF)-ICT (2-3 cycles) for larynx preservation at our institution between 2004 and 2013, were included in this retrospective study. Prognostic factors of oncologic (overall, cause-specific and recurrence-free survival: OS, SS and RFS) and functional (dysphagia outcome and severity scale, permanent enteral nutrition, larynx preservation) outcomes were assessed in univariate and multivariate analyses. A total of 53 patients (42 men and 11 women, mean age 58.6 +/- 8.2 years) were included in this study. Grade 3-4 toxicities were experienced by 17 (32 %) patients during ICT. The rate of poor response (response <50 % without larynx remobilization) to ICT was 10 %. At 5 years, OS, SS and RFS rates were 56, 60 and 54 %, respectively. Four patients required definitive enteral nutrition (permanent enteral tube feeding). The rate of patients alive, disease-free and with a functional larynx at 2 years was 58 %. T4 tumor stage (p = 0.005) and response to ICT <50 % (p = 0.02) were independent prognostic factors of OS. Response to ICT was significantly associated with the risk of permanent enteral nutrition (p = 0.04) and larynx preservation (p = 0.01). In daily clinical practice, a TPF-ICT-based larynx preservation protocol can be used in patients with locally advanced hypopharyngeal cancer with satisfactory results in terms of tolerance, efficacy and oncologic and functional outcomes. PMID- 26858200 TI - Novel factors of Anopheles gambiae haemocyte immune response to Plasmodium berghei infection. AB - BACKGROUND: Insect haemocytes mediate cellular immune responses (e.g., phagocytosis) and contribute to the synthesis of humoral immune factors. In previous work, a genome-wide molecular characterization of Anopheles gambiae circulating haemocytes was followed by functional gene characterization using cell-based RNAi screens. Assays were carried out to investigate the role of selected haemocyte-specific or enriched genes in phagocytosis of bacterial bio particles, expression of the antimicrobial peptide cecropin1, and basal and induced expression of the mosquito complement factor LRIM1 (leucine-rich repeat immune gene I). FINDINGS: Here we studied the impact of a subset of genes (37 candidates) from the haemocyte-specific dsRNA collection on the development of Plasmodium in the mosquito by in vivo gene silencing. Our screening identifies 10 novel factors with a role in the mosquito response to Plasmodium. Analysis of in vivo screening phenotypes reveals a significant anti-correlation between the prevalence of oocysts and melanised ookinetes. CONCLUSIONS: Among novel immune genes are putative pattern recognition proteins (leucine-rich repeat, fibrinogen domain and R-type lectins), immune modulation and signalling proteins (LPS induced tumor necrosis factor alpha factor, LITAF and CLIP proteases), and components of extracellular matrix such as laminin and collagen. Additional identified proteins such as the storage protein hexamerin and vesicular-type ATPase (V-ATPase) are associated for the first time with the mosquito response against Plasmodium. PMID- 26858199 TI - The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment. AB - Myeloid-derived suppressor cells (MDSC) are one of the major components of the tumor microenvironment. The main feature of these cells is their potent immune suppressive activity. MDSC are generated in the bone marrow and, in tumor-bearing hosts, migrate to peripheral lymphoid organs and the tumor to contribute to the formation of the tumor microenvironment. Recent findings have revealed differences in the function and fate of MDSC in the tumor and peripheral lymphoid organs. We review these findings here and, in this context, we discuss the current understanding as to the nature of these differences, the underlying mechanisms, and their potential impact on the regulation of tumor progression. PMID- 26858201 TI - Automated longitudinal monitoring of in vivo protein aggregation in neurodegenerative disease C. elegans models. AB - BACKGROUND: While many biological studies can be performed on cell-based systems, the investigation of molecular pathways related to complex human dysfunctions - e.g. neurodegenerative diseases - often requires long-term studies in animal models. The nematode Caenorhabditis elegans represents one of the best model organisms for many of these tests and, therefore, versatile and automated systems for accurate time-resolved analyses on C. elegans are becoming highly desirable tools in the field. RESULTS: We describe a new multi-functional platform for C. elegans analytical research, enabling automated worm isolation and culture, reversible worm immobilization and long-term high-resolution imaging, and this under active control of the main culture parameters, including temperature. We employ our platform for in vivo observation of biomolecules and automated analysis of protein aggregation in a C. elegans model for amyotrophic lateral sclerosis (ALS). Our device allows monitoring the growth rate and development of each worm, at single animal resolution, within a matrix of microfluidic chambers. We demonstrate the progression of individual protein aggregates, i.e. mutated human superoxide dismutase 1 - Yellow Fluorescent Protein (SOD1-YFP) fusion proteins in the body wall muscles, for each worm and over several days. Moreover, by combining reversible worm immobilization and on-chip high-resolution imaging, our method allows precisely localizing the expression of biomolecules within the worms' tissues, as well as monitoring the evolution of single aggregates over consecutive days at the sub-cellular level. We also show the suitability of our system for protein aggregation monitoring in a C. elegans Huntington disease (HD) model, and demonstrate the system's ability to study long-term doxycycline treatment-linked modification of protein aggregation profiles in the ALS model. CONCLUSION: Our microfluidic-based method allows analyzing in vivo the long-term dynamics of protein aggregation phenomena in C. elegans at unprecedented resolution. Pharmacological screenings on neurodegenerative disease C. elegans models may strongly benefit from this method in the near future, because of its full automation and high-throughput potential. PMID- 26858205 TI - Reply to: "Neurosurgical resident education in Europe--results of a multinational survey". PMID- 26858202 TI - Functional characterization of blue-light-induced responses and PHOTOTROPIN 1 gene in Welwitschia mirabilis. AB - The blue light (BL) receptor phototropin (phot) is specifically found in green plants; it regulates various BL-induced responses such as phototropism, chloroplast movement, stomatal opening, and leaf flattening. In Arabidopsis thaliana, two phototropins--phot1 and phot2--respond to blue light in overlapping but distinct ways. These BL-receptor-mediated responses enhance the photosynthetic activity of plants under weak light and minimize photodamage under strong light conditions. Welwitschia mirabilis Hook.f. found in the Namib Desert, and it has adapted to severe environmental stresses such as limiting water and strong sunlight. Although the plant has physiologically and ecologically unique features, it is unknown whether phototropin is functional in this plant. In this study, we assessed the functioning of phot-mediated BL responses in W. mirabilis. BL-dependent phototropism and stomatal opening was observed but light-dependent chloroplast movement was not detected. We performed a functional analysis of the PHOT1 gene of W. mirabilis, WmPHOT1, in Arabidopsis thaliana. We generated transgenic A. thaliana lines expressing WmPHOT1 in a phot1 phot2 double mutant background. Several Wmphot1 transgenic plants showed normal growth, although phot1 phot2 double mutant plants showed stunted growth. Furthermore, Wmphot1 transgenic plants showed normal phot1-mediated responses including phototropism, chloroplast accumulation, stomatal opening, and leaf flattening, but lacked the chloroplast avoidance response that is specifically mediated by phot2. Thus, our findings indicate that W. mirabilis possesses typical phot-mediated BL responses that were at least partially mediated by functional phototropin 1, an ortholog of Atphot1. PMID- 26858203 TI - Computerized tomography angiography in preoperative assessment of intravenous leiomyomatosis extending to inferior vena cava and heart. AB - BACKGROUND: Intravenous leiomyomatosis (IVL) extending to inferior vena cava and heart is one of the most challenging conditions for surgical treatment. We explored the use of computerized tomography angiography (CTA) in preoperative assessment for this disease. METHODS: A cohort of 31 patients with IVL extending to inferior vena cava and heart were reviewed from the year 2002 to 2014, focusing on the preoperative CTA imaging characteristics and the surgical procedures in clinical treatment. RESULTS: All patients were diagnosed correctly combining the clinical medical history and CTA imaging. Thirteen patients had tumors confined within the inferior vena cava, and 18 patients had tumors intruding into the right heart. Furthermore, 15 tumors were located in the right atrium alone, and 3 tumors involved both the right atrium and the right ventricle. All patients had simple or multiple soft tissue masses from the pelvis, with 22 tumors extending into inferior vena cava through the iliac veins and 9 tumors through the ovarian veins. Three patients had tumors invading into lung and underwent tumor thrombus resection in the pulmonary artery. Patients received either one-stage surgery or two-stage surgery dependent on patient general condition and tumor status. All operations were successfully performed by multidisciplinary cooperation, including gynecology, cardiac surgery, and vascular surgery, without severe surgical-related complications or deaths. CONCLUSIONS: CTA imaging can present location, size, and full-scale extension pathway of IVL lesions, and can be used as first-line imaging technique in preoperative assessment, having great significance in making surgical plan and obtaining successful outcome. PMID- 26858204 TI - The Role of the ncRNA RgsA in the Oxidative Stress Response and Biofilm Formation in Azotobacter vinelandii. AB - Azotobacter vinelandii is a soil bacterium that forms desiccation-resistant cysts, and the exopolysaccharide alginate is essential for this process. A. vinelandii also produces alginate under vegetative growth conditions, and this production has biotechnological significance. Poly-beta-hydroxybutyrate (PHB) is another polymer synthetized by A. vinelandii that is of biotechnological interest. The GacS/A two-component signal transduction system plays an important role in regulating alginate production, PHB synthesis, and encystment. GacS/A in turn controls other important regulators such as RpoS and the ncRNAs that belong to the Rsm family. In A. vinelandii, RpoS is necessary for resisting oxidative stress as a result of its control over the expression of the catalase Kat1. In this work, we characterized a new ncRNA in A. vinelandii that is homologous to the P16/RsgA reported in Pseudomonas. We found that the expression of rgsA is regulated by GacA and RpoS and that it was essential for oxidative stress resistance. However, the activity of the catalase Kat1 is unaffected in rgsA mutants. Unlike those reported in Pseudomonas, RgsA in A. vinelandii regulates biofilm formation but not polymer synthesis or the encystment process. PMID- 26858206 TI - Endovascular treatment of ruptured blood blister-like aneurysms with multiple (>=3) overlapping Enterprise stents and coiling. AB - BACKGROUND: Blood blister-like aneurysms (BBAs) are difficult to treat both surgically and endovascularly, and the optimal treatment remains controversial. The aim of this study was to evaluate the clinical and angiographic feasibility of multiple overlapping stents (>=3) with coiling for treating BBA. METHODS: A retrospective review from four institutions identified ten patients with ruptured BBAs who were treated with multiple overlapping stents (>=3). We included both the patients who were initially treated with more than three stents and those who eventually had more than three stents as a consequence of retreatment. Angiographic results (Raymond scale), clinical outcomes (mRS) and treatment courses were evaluated. RESULTS: Initially, seven patients were treated with triple stents and three with double stents. Immediate angiographic results revealed that six aneurysms were Raymond grade 1, three were grade 2, and one was grade 3. Complementary treatment was required in four patients. All three patients who were initially treated with double stents required complementary treatment (100 %). One patient required complementary treatment among the seven patients who were initially treated with three stents (14.3 %). The last follow up angiography (mean, 12.2 +/- 14.7 months; range, 1-44 months) revealed grade 1 in all ten patients. Clinical data (mean follow-up period, 18.2 +/- 20.1 months; range, 1-62 months) revealed eight patients with a mRS score of 0-2 and two with mRS 3-5. CONCLUSIONS: Even in the era of flow diverter stents, multiple overlapping stents (>=3) with coiling could be a feasible alternative for treating ruptured BBAs. Additional experience and follow-up are needed in a larger series to state the long-term efficacy of this treatment. PMID- 26858207 TI - Cochlear implants in the etiopathogenesis of glioblastoma--an interesting observation or independent finding? AB - Various risk factors have been implicated in the pathogenesis of glioblastomas including ionizing radiation. Recent evidence has suggested a possible association between exposure to nonionizing radiofrequency electromagnetic fields (RF-EMF) generated from mobile phones and wireless devices to cause malignant transformation of the neuroglial cells, albeit this is widely debated. In this report, we discuss the development of glioblastoma in two geopolitically unrelated patients, an elderly male from the United States and a middle-aged woman from Sweden, with long-standing cochlear implants (CI). We hypothesize that the low-frequency RF-EMF emanating from the transcutaneous link of the CI prosthesis over a long period has potentially triggered tumor development in these patients. PMID- 26858208 TI - The efficacy of gamma knife radiosurgery alone as a primary treatment for intracranial dural arteriovenous fistulas. AB - BACKGROUND: The application of gamma knife radiosurgery (GKRS) alone has been expanded for dural arteriovenous fistulas (DAVFs). However, a standardized protocol delineating the appropriate circumstances for GKRS alone in cases of DAVF has yet to be determined. The purpose of this study was to report a single center's treatment algorithm for GKRS alone as a primary treatment for intracranial DAVFs and assess related clinical and radiological data. METHOD: Among 31 DAVF patients treated according to our institute's treatment algorithm between February 2009 and November 2014, 20 patients underwent GKRS alone. DAVF patients treated with GKRS alone fell in two main subgroups: DAVF patients without cortical venous reflux (CVR) but with symptoms (n = 8) and DAVF patients with CVR but without a high bleeding risk (defined as CVR with aggressive symptoms including hemorrhage or non-hemorrhagic neurological deficit, n = 11). One DAVF patient with a high bleeding risk had GKRS alone because of difficult endovascular access. Mean radiation volume was 4.8 cc (range, 0.7-14.2 cc), and mean maximal dose was 33.5 Gy (range, 28-38 Gy). RESULTS: At mean follow-up of 29.1 months (range, 8-69 months), radiological findings demonstrated complete cures in 18 patients (90 %) and subtotal cures in 2 patients (10 %). One patient had a transient complication, but no neurologic sign. All symptomatic patients showed complete resolution. CONCLUSIONS: Our treatment algorithm showed GKRS alone may serve as a primary treatment for patients with DAVFs regardless of location and presence of CVR, unless there is a high bleeding risk. However, a multicenter, prospective study is necessary to generalize our treatment algorithm. PMID- 26858209 TI - Peripheral nerve field stimulation for chronic neuropathic pain: a single institution experience. AB - BACKGROUND: Peripheral nerve field stimulation (PNFS) is a novel neurosurgical procedure consisting of implantation of subcutaneous leads in specific painful areas in different types of painful, drug-resistant syndromes. The objective of this study was to evaluate the efficacy of PNFS in several patients affected by different chronic neuropathic pain syndromes, along with its risks, limits and possible correlation between the results achieved and the patients' main symptoms. METHODS: Twenty-two patients affected by different types of chronic neuropathic pain were submitted to PNFS at the Department of Neurosurgery of the Istituto Neurologico "C. Besta" in Milan between July 2009 and July 2013. The visual analog scale (VAS) and variations in the use of analgesic drugs, along with complications, were considered to assess results. RESULTS: In 59 % of our patients, an average pain reduction of 5.50 points on the visual analog scale was observed (average pre-implant score 8.86 and average post-implant score 3.36). These patients reduced their analgesic drug use after PNFS. We observed no early or long-term complications after our last follow-up evaluation. CONCLUSIONS: PNFS can be considered an effective and safe option to treat carefully selected, drug resistant and chronic neuropathic pain patients; the reversibility of the procedure and its lack, at least in our hands, of long-term complications may contribute to wider use of this procedure. PMID- 26858210 TI - The effect of metformin on prolactin levels in patients with drug-induced hyperprolactinemia. AB - BACKGROUND: In bromocriptine-treated hyperprolactinemic patients with impaired glucose tolerance, metformin was found to reduce plasma levels of prolactin. No previous study has investigated its impact on plasma prolactin in patients with drug-induced hyperprolactinemia. METHODS: The study included 20 women with antipsychotic-induced hyperprolactinemia and 12 normoprolactinemic women, who, because of coexisting glucose metabolism abnormalities, were treated for 6months with metformin. Hyperprolactinemic patients with prediabetes received moderate doses of metformin (1.7g daily), while hyperprolactinemic and normoprolactinemic patients with type 2 diabetes were treated with high-dose metformin (2.55-3g daily). Fasting plasma glucose levels, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), glycated hemoglobin, as well as plasma levels of prolactin, thyrotropin, adrenocorticotropic hormone and insulin-like growth factor-1 were assessed at baseline and after 6months of treatment. RESULTS: Despite reducing plasma glucose, HOMA1-IR, and glycated hemoglobin in all treatment groups, metformin decreased prolactin levels only if given at high doses to patients with elevated prolactin levels. No changes in thyrotropin, adrenocorticotropic hormone, and insulin-like growth factor-1 were observed in any treatment groups. CONCLUSIONS: The obtained results suggest that the effect of metformin on plasma prolactin depends on its dose and is observed only in patients with elevated levels of this hormone. PMID- 26858211 TI - The effects of anesthetic agents on pupillary function during general anesthesia using the automated infrared quantitative pupillometer. AB - Pupil reactivity can be used to evaluate central nervous system function and can be measured using a quantitative pupillometer. However, whether anesthetic agents affect the accuracy of the technique remains unclear. We examined the effects of anesthetic agents on pupillary reactivity. Thirty-five patients scheduled for breast or thyroid surgery were enrolled in the study. Patients were divided into four groups based on the technique used to maintain anesthesia: a sevoflurane remifentanil (SEV/REM) group, a sevoflurane (SEV) group, a desflurane remifentanil (DES/REM) group, and a propofol-remifentanil (PRO/REM) group. We measured maximum resting pupil size (MAX), reduction pupil size ratio (%CH), latency duration (LAT) and neurological pupil index (NPi). A marked reduction in MAX and %CH compared with baseline was observed in all groups, but LAT was unchanged during surgery. NPi reduced within the first hour of surgery in the SEV/REM, SEV, and DES/REM groups, but was not significantly different in the PRO/REM group. Compared with the PRO/REM group, mean %CH and NPi in patients anesthetized with SEV/REM, SEV or DES/REM were markedly lower at 1 h after surgery had commenced. There was no correlation between NPi and bispectral index. Fentanyl given alone decreased pupil size and %CH in light reflex, but did not change the NPi. NPi was decreased by inhalational anesthesia not but intravenous anesthesia. The difference in pupil reactivity between inhalational anesthetic and propofol may indicate differences in the alteration of midbrain reflexs in patients under inhalational or intravenous anesthesia. PMID- 26858212 TI - The Role of Cannabinoids in Neuroanatomic Alterations in Cannabis Users. AB - The past few decades have seen a marked change in the composition of commonly smoked cannabis. These changes primarily involve an increase of the psychoactive compound ?(9)-tetrahydrocannabinol (THC) and a decrease of the potentially therapeutic compound cannabidiol (CBD). This altered composition of cannabis may be linked to persistent neuroanatomic alterations typically seen in regular cannabis users. In this review, we summarize recent findings from human structural neuroimaging investigations. We examine whether neuroanatomic alterations are 1) consistently observed in samples of regular cannabis users, particularly in cannabinoid receptor-high areas, which are vulnerable to the effects of high circulating levels of THC, and 2) associated either with greater levels of cannabis use (e.g., higher dosage, longer duration, and earlier age of onset) or with distinct cannabinoid compounds (i.e., THC and CBD). Across the 31 studies selected for inclusion in this review, neuroanatomic alterations emerged across regions that are high in cannabinoid receptors (i.e., hippocampus, prefrontal cortex, amygdala, cerebellum). Greater dose and earlier age of onset were associated with these alterations. Preliminary evidence shows that THC exacerbates, whereas CBD protects from, such harmful effects. Methodologic differences in the quantification of levels of cannabis use prevent accurate assessment of cannabis exposure and direct comparison of findings across studies. Consequently, the field lacks large "consortium-style" data sets that can be used to develop reliable neurobiological models of cannabis-related harm, recovery, and protection. To move the field forward, we encourage a coordinated approach and suggest the urgent development of consensus-based guidelines to accurately and comprehensively quantify cannabis use and exposure in human studies. PMID- 26858213 TI - Disadvantage of Social Sensitivity: Interaction of Oxytocin Receptor Genotype and Child Maltreatment on Brain Structure. AB - BACKGROUND: Oxytocin has received much attention as a prosocial and anxiolytic neuropeptide. In human studies, the G-allele of a common variant (rs53576) in the oxytocin receptor gene (OXTR) has been associated with protective properties such as reduced stress response and higher receptiveness for social support. In contrast, recent studies suggest a detrimental role of the rs53576 G-allele in the context of childhood maltreatment. To further elucidate the role of OXTR, gene by maltreatment interactions on brain structure and function were investigated. METHODS: Three hundred nine healthy participants genotyped for OXTR rs53576 underwent structural as well as functional magnetic resonance imaging during a common emotional face-matching task. Childhood maltreatment was assessed with the Childhood Trauma Questionnaire (CTQ). Gray matter volumes were investigated by means of voxel-based morphometry across the entire brain. RESULTS: Structural magnetic resonance imaging data revealed a strong interaction of rs53576 genotype and CTQ scores, mapping specifically to the bilateral ventral striatum. GG homozygotes but not A-allele carriers showed strong gray matter reduction with increasing CTQ scores. In turn, lower ventral striatum gray matter volumes were associated with lower reward dependence, a prosocial trait. Furthermore, the G-allele was associated with increased amygdala responsiveness to emotional facial expressions. CONCLUSIONS: The findings suggest that the G allele constitutes a vulnerability factor for specific alterations of limbic brain structure in individuals with adverse childhood experiences, complemented by increased limbic responsiveness to emotional interpersonal stimuli. While oxytocinergic signaling facilitates attachment and bonding in supportive social environments, this attunement for social cues may turn disadvantageous under early adverse conditions. PMID- 26858214 TI - Acute and Chronic Effects of Cannabinoids on Human Cognition-A Systematic Review. AB - Cannabis use has been associated with impaired cognition during acute intoxication as well as in the unintoxicated state in long-term users. However, the evidence has been mixed and contested, and no systematic reviews of the literature on neuropsychological task-based measures of cognition have been conducted in an attempt to synthesize the findings. We systematically review the empirical research published in the past decade (from January 2004 to February 2015) on acute and chronic effects of cannabis and cannabinoids and on persistence or recovery after abstinence. We summarize the findings into the major categories of the cognitive domains investigated, considering sample characteristics and associations with various cannabis use parameters. Verbal learning and memory and attention are most consistently impaired by acute and chronic exposure to cannabis. Psychomotor function is most affected during acute intoxication, with some evidence for persistence in chronic users and after cessation of use. Impaired verbal memory, attention, and some executive functions may persist after prolonged abstinence, but persistence or recovery across all cognitive domains remains underresearched. Associations between poorer performance and a range of cannabis use parameters, including a younger age of onset, are frequently reported. Little further evidence has emerged for the development of tolerance to the acutely impairing effects of cannabis. Evidence for potential protection from harmful effects by cannabidiol continues to increase but is not definitive. In light of increasing trends toward legalization of cannabis, the knowledge gained from this body of research needs to be incorporated into strategies to minimize harm. PMID- 26858216 TI - In Memoriam: Masaya Segawa, MD, PhD (1936-2014). PMID- 26858215 TI - Essential Role of Mesolimbic Brain-Derived Neurotrophic Factor in Chronic Social Stress-Induced Depressive Behaviors. AB - BACKGROUND: Previous work has shown that chronic social defeat stress (CSDS) induces increased phasic firing of ventral tegmental area (VTA) dopamine (DA) neurons that project to the nucleus accumbens (NAc) selectively in mice that are susceptible to the deleterious effects of the stress. In addition, acute optogenetic phasic stimulation of these neurons promotes susceptibility in animals exposed to acute defeat stress. These findings are paradoxical, as increased DA signaling in NAc normally promotes motivation and reward, and the influence of chronic phasic VTA firing in the face of chronic stress is unknown. METHODS: We used CSDS with repeated optogenetic activation and pharmacologic manipulations of the mesolimbic VTA-NAc pathway to examine the role of brain derived neurotrophic factor (BDNF) and DA signaling in depressive-like behaviors. We measured BDNF protein expression and DA release in this model. RESULTS: Pharmacologic blockade of BDNF-tyrosine receptor kinase B (TrkB) signaling, but not DA signaling, in NAc prevented CSDS-induced behavioral abnormalities. Chronic optogenetic phasic stimulation of the VTA-NAc circuit during CSDS exacerbated the defeat-induced behavioral symptoms, and these aggravated symptoms were also normalized by BDNF-TrkB blockade in NAc. The aggravated behavioral deficits induced by phasic stimulation of the VTA-NAc pathway were blocked as well by local knockdown of BDNF in VTA. CONCLUSIONS: These findings show that BDNF-TrkB signaling, rather than DA signaling, in the VTA-NAc circuit is crucial for facilitating depressive-like outcomes after CSDS and they establish BDNF-TrkB signaling as a pathologic mechanism during periods of chronic stress. PMID- 26858217 TI - Cerebral Hemodynamics in Asphyxiated Newborns Undergoing Hypothermia Therapy: Pilot Findings Using a Multiple-Time-Scale Analysis. AB - BACKGROUND: Improved quantitative assessment of cerebral hemodynamics in newborns might enable us to optimize cerebral perfusion. Our objective was to develop an approach to assess cerebral hemodynamics across multiple time scales during the first 72 hours of life in newborns during hypothermia therapy. METHODS: Spontaneous oscillations in mean arterial pressure and regional cerebral tissue oxygen saturation were analyzed using a moving window correlation method with time scales ranging from 0.15 to 8 hours in this pilot methodology study. Abnormal neurodevelopmental outcome was defined by Bayley III scores and/or cerebral palsy by age 24 months using receiver operating curve. RESULTS: Multiple time-scale correlations between the mean arterial pressure and regional cerebral tissue oxygen saturation oscillations were tested in 10 asphyxiated newborns undergoing hypothermia therapy. Large noninduced fluctuations in the blood pressure were observed during cooling in all five infants with abnormal outcomes. Notably, these infants had two distinct patterns of correlation: a positive in phase correlation at the short time scales (15 minutes) and/or a negative antiphase correlations observed at long time scales (4 hours.). Both the in-phase (area under the curve 0.6, [95% confidence interval 0.2-0.95]) and antiphase correlations (area under the curve 0.75, [95% confidence interval 0.4-0.95]) appeared to be related to an abnormal outcome. CONCLUSIONS: Our observations suggest that the time scale is an important factor that needs to be standardized in the assessment of neonatal cerebral hemodynamics. PMID- 26858218 TI - Integration of Provider, Pharmacy, and Patient-Reported Data to Improve Medication Adherence for Type 2 Diabetes: A Controlled Before-After Pilot Study. AB - BACKGROUND: Patients with diabetes often have poor adherence to using medications as prescribed. The reasons why, however, are not well understood. Furthermore, most health care delivery processes do not routinely assess medication adherence or the factors that contribute to poor adherence. OBJECTIVE: The objective of the study was to assess the feasibility of an integrated informatics approach to aggregating and displaying clinically relevant data with the potential to identify issues that may interfere with appropriate medication utilization and facilitate patient-provider communication during clinical encounters about strategies to improve medication use. METHODS: We developed a clinical dashboard within an electronic health record (EHR) system that uses data from three sources: the medical record, pharmacy claims, and a patient portal. Next, we implemented the dashboard into three community health centers. Health care providers (n=15) and patients with diabetes (n=96) were enrolled in a before after pilot to test the system's impact on medication adherence and clinical outcomes. To measure adherence, we calculated the proportion of days covered using pharmacy claims. Demographic, laboratory, and visit data from the EHR were analyzed using pairwise t tests. Perceived barriers to adherence were self reported by patients. Providers were surveyed about their use and perceptions of the clinical dashboard. RESULTS: Adherence significantly and meaningfully improved (improvements ranged from 6%-20%) consistently across diabetes as well as cardiovascular drug classes. Clinical outcomes, including HbA1c, blood pressure, lipid control, and emergency department utilization remained unchanged. Only a quarter of patients (n=24) logged into the patient portal and completed psychosocial questionnaires about their barriers to taking medications. CONCLUSIONS: Integrated approaches using advanced EHR, clinical decision support, and patient-controlled technologies show promise for improving appropriate medication use and supporting better management of chronic conditions. Future research and development is necessary to design, implement, and integrate the myriad of EHR and clinical decision support systems as well as patient-focused information systems into routine care and patient processes that together support health and well-being. PMID- 26858219 TI - Comparison of the Ventral Epidural Spreading in Modified Interlaminar Approach and Transforaminal Approach: A Randomized, Double-Blind Study. AB - OBJECTIVE: To evaluate the effectiveness of a modified interlaminar (MIL) approach for accessing ventral epidural space compared with the transforaminal (TF) approach. STUDY DESIGN: Randomized double blinded control trial METHODS: Eighty-four patients with lumbar radicular pain were randomly assigned into two groups in which drug delivery to the ventral epidural space was performed through either the MIL (n = 42) or the TF approach (n = 42). Within each group, subgroups were classified according to the dominant pathology as assessed by magnetic resonance imaging (MRI): bulging disc, herniated nucleus pulposus (HNP), and foraminal stenosis. Degenerative changes such as scoliosis and facet hypertrophy was also evaluated. RESULTS: The overall accessibility to the ventral epidural space was similar between the two groups. In cases with foraminal stenosis, the success rate of ventral epidural spreading was significantly higher in the MIL group compared with the TF group (TF approach = 50.00% vs MIL approach = 100.00%, P = 0.013). Medial spread of contrast was more dominant in the MIL group (P < 0.001). There was no significant difference between the two groups in overall clinical outcome. The total success rate of accessing the ventral epidural space in degenerative bony changes was higher in the MIL group than in the TF group (TF approach = 57.1% vs MIL approach = 84.6%), but the difference was not statistically significant. CONCLUSION: In cases where access to the ventral epidural space by conventional approach is limited, our MIL approach can be considered a suitable alternative, especially in the case of foraminal stenosis. PMID- 26858220 TI - Dysfunctional Relationship Between the Prefrontal Cortex and Amygdala for Explaining Posttraumatic CRPS Syndrome. PMID- 26858227 TI - [Lichenoid reaction to red pigment in a tattoo]. PMID- 26858228 TI - [Uncommon complication in thyroid surgery]. PMID- 26858229 TI - [Quality of life and associated factors in asthma in a Primary Care Center. Application of the reduced version of the Asthma Quality of Life Questionnaire]. AB - INTRODUCTION: Asthma is a highly prevalent disease that can affect the quality of life (QoL). The objective of this study is to determine the QoL in patients with asthma and its relationship with different factors in a Primary Care centre. MATERIAL AND METHODS: A descriptive, cross-sectional study was conducted in an urban health centre. The study included a total of 243 patients between 17 to 70 years who had a diagnosis of asthma in their medical records. The QoL was measured using the Spanish version of the Mini-Asthma Quality of Life Questionnaire, with age, sex, smoking, anxiety, depression, severity and control of asthma as associated variables. RESULTS: The mean age was 44.5 years and 71.2% were women. More than half (54.3%) had intermittent asthma, and 45.7% persistent asthma. The overall score in the Mini-Asthma Quality of Life Questionnaire was 5.4 out of 7. The scores by dimensions were: symptoms 5.4; limitation of activities 5.8; emotional function 5.7, and environmental stimuli 4.7. The variables with a worse QoL score that remained statistically significant (P<.05) in the multivariate analysis were poor control of asthma (in all dimensions), history of depression (in all except environmental stimuli), educated to less than secondary level (symptoms and emotional function), and patients admitted to hospital in the past 3 years (symptoms) and who used long-term beta-adrenergics (emotional function). CONCLUSIONS: Patients with intermittent, mild and moderate asthma have a good QoL. Poor control of the asthma and a history of depression negatively affect the QoL. PMID- 26858230 TI - [Epidemiological characteristics of patients evaluated with fibromyalgia in the Assessment of Disability Unit of Madrid]. AB - OBJECTIVE: To determine the epidemiological characteristics of patients with fibromyalgia requiring assessment of incapacity for work. METHOD: A descriptive study was conducted on the patients evaluated in the Medical Unit of the National Institute of Social Security in Madrid in the period from 2005 to 2014 with the diagnosis of fibromyalgia. A study was made on the variables: age, sex, marital status, comorbidity (hypothyroidism, neck pain, psychiatric disorders, and carpal tunnel syndrome), professional occupation, level of education, and type of affiliation to the National Institute of Social Security. RESULT: The total number of patients studied was 5,501. The median age was 53 years. Compared to the general working population in our area there were 47% more women, 12% less married people, 25% less workers with higher education, and 23% more unskilled occupations. As regards the working population in our area, there is a markedly increased prevalence of neck pain (prevalence ratio: 2.0), hypothyroidism (prevalence ratio 2.4), and carpal tunnel syndrome (prevalence ratio: 3.0). More than half (58%) of the sample presented with psychiatric disorders. CONCLUSION: It can be concluded that the profile of the patient with fibromyalgia assessed in the UMEVI is a woman, aged 46-60 years, mostly with a relatively unskilled job, and with primary level education. More than half of the cases had associated psychiatric disorders, and often associated with neck pain diagnoses, carpal tunnel syndrome, and hypothyroidism. PMID- 26858231 TI - Elevated Autism Spectrum Disorder Traits in Young Children with OCD. AB - Studies have shown a high prevalence of autistic spectrum traits in both children and adults with psychiatric disorders; however the prevalence rate has not yet been investigated in young children with OCD. The aim of the current study was to (1) determine whether ASD traits indicated by the Social Communication Questionnaire (SCQ) and the Social Responsiveness Scale (SRS) were elevated in young children with OCD who do not have a specific ASD diagnosis and (2) determine if ASD traits were associated with OCD severity. Participants (N = 127) were children ages 5-8 years enrolled in the pediatric obsessive-compulsive disorder treatment study for young children (POTS Jr.). Results indicated that the SRS showed elevated autistic traits in the sample and was associated with OCD severity whereas the SCQ did not indicate heightened ASD symptoms. Implications of these results are discussed. PMID- 26858232 TI - Unaccompanied Immigrant Minors: Where to Begin. AB - The number of unaccompanied immigrant minors (UIMs) from Central America significantly increased in 2014. Nearly 50,000 children from El Salvador, Guatemala, and Honduras crossed the United States-Mexico border in 2014, compared with 3,933 in 2011. Few resources exist to guide pediatric nurse practitioners (PNPs) in their care of UIM. The multifactorial reasons behind migration and the state of children's health in Central America provide insight into the needs of UIMs. Guidelines for similar groups such as foreign-born children and refugees offer direction for the health care considerations of UIMs. This article provides demographic information on UIMs, highlights the unique and challenging medical and mental health issues facing UIMs, and discusses the role of the PNP. A UIM's initial visit with a PNP serves as an opportunity to build trust through culturally competent, trauma-informed care, provide preventive care, assess for unmet health needs, and screen for mental health conditions. PMID- 26858233 TI - Aniceto Baltasar, MD. PMID- 26858234 TI - The cardiovascular risk reduction benefits of a low-carbohydrate diet outweigh the potential increase in LDL-cholesterol. PMID- 26858235 TI - Corticosteroids in women at risk of late preterm delivery may reduce respiratory complications in newborns. PMID- 26858236 TI - Ten transgenic animal research conferences and counting. PMID- 26858238 TI - Erratum to: Giovanni Battista Morgagni: facial reconstruction by virtual anthropology. PMID- 26858237 TI - Hsp90 Inhibition Results in Glucocorticoid Receptor Degradation in Association with Increased Sensitivity to Paclitaxel in Triple-Negative Breast Cancer. AB - Targetable molecular drivers for triple-negative breast cancer (TNBC) have been difficult to identify; therefore, standard treatment remains limited to conventional chemotherapy. Recently, new-generation small-molecule Hsp90 inhibitors (e.g., ganetespib and NVP-AUY922) have demonstrated improved safety and activity profiles over the first-generation ansamycin class. In breast cancer, clinical responses have been observed in a subset of TNBC patients following ganetespib monotherapy; however, the underlying biology of Hsp90 inhibitor treatment and tumor response is not well understood. Glucocorticoid receptor (GR) activity in TNBC is associated with chemotherapy resistance. Here, we find that treatment of TNBC cell lines with ganetespib resulted in GR degradation and decreased GR-mediated gene expression. Ganetespib-associated GR degradation also sensitized TNBC cells to paclitaxel-induced cell death both in vitro and in vivo. The beneficial effect of the Hsp90 inhibitor on paclitaxel induced cytotoxicity was reduced when GR was depleted in TNBC cells but could be recovered with GR overexpression. These findings suggest that GR-regulated anti apoptotic and pro-proliferative signaling networks in TNBC are disrupted by Hsp90 inhibitors, thereby sensitizing TNBC to paclitaxel-induced cell death. Thus, GR+ TNBC patients may be a subgroup of breast cancer patients who are most likely to benefit from adding an Hsp90 inhibitor to taxane therapy. PMID- 26858240 TI - Landfill mining: Development of a cost simulation model. AB - Landfill mining permits recovering secondary raw materials from landfills. Whether this purpose is economically feasible, however, is a matter of various aspects. One is the amount of recoverable secondary raw material (like metals) that can be exploited with a profit. Other influences are the costs for excavation, for processing the waste at the landfill site and for paying charges on the secondary disposal of waste. Depending on the objectives of a landfill mining project (like the recovery of a ferrous and/or a calorific fraction) these expenses and revenues are difficult to assess in advance. This situation complicates any previous assessment of the economic feasibility and is the reason why many landfills that might be suitable for landfill mining are continuingly operated as active landfills, generating aftercare costs and leaving potential hazards to later generations. This article presents a newly developed simulation model for landfill mining projects. It permits identifying the quantities and qualities of output flows that can be recovered by mining and by mobile on-site processing of the waste based on treatment equipment selected by the landfill operator. Thus, charges for disposal and expected revenues from secondary raw materials can be assessed. Furthermore, investment, personnel, operation, servicing and insurance costs are assessed and displayed, based on the selected mobile processing procedure and its throughput, among other things. For clarity, the simulation model is described in this article using the example of a real Austrian sanitary landfill. PMID- 26858241 TI - Trends in hospital admissions involving suicidal behaviour in the Northern Territory, 2001-2013. AB - OBJECTIVE: To investigate trends in hospital admissions involving suicidal behaviour in the Northern Territory (NT) resident population over the period 2001 2013. METHODS: Estimates of age-standardised rates and average changes in the annual rate of hospital admissions involving suicidal behaviour were calculated by socio-demographic characteristics and types of suicidal behaviour. RESULTS: Overall rates for Indigenous admissions were 2.7 times higher than non-Indigenous admissions and had increased by almost twice as much. While male and female rates of admission were similar for both Indigenous and non-Indigenous residents, the average annual change in rates was greater for Indigenous females (13.4%) compared to males (8.8%) and for non-Indigenous males (7.7%) compared to females (5.2%). Younger and middle-aged Indigenous admissions experienced increasing rates of admissions, whilst trends were similar across age groups for non Indigenous admissions. Admissions with a diagnosis of suicidal ideation increased the most across all groups. Trends in intentional self-harm admissions differed according to Indigenous status and sex. CONCLUSIONS: There have been substantial increases in hospital admissions involving suicidal behaviour in the NT, most markedly for Indigenous residents. Indigenous females and youth appear to be at increasing risk. The steep increase in suicidal ideation across all groups warrants further investigation. PMID- 26858239 TI - Pharmacotherapy for Fragile X Syndrome: Progress to Date. AB - To date, no drug is approved for the treatment of Fragile X Syndrome (FXS) although many drugs are used to manage challenging behaviors from a symptomatic perspective in this population. While our understanding of FXS pathophysiology is expanding, efforts to devise targeted FXS-specific treatments have had limited success in placebo-controlled trials. Compounds aimed at rectifying excessive glutamate and deficient gamma-aminobutyric acid (GABA) neurotransmission, as well as other signaling pathways known to be affected by Fragile X Mental Retardation Protein (FMRP) are under various phases of development in FXS. With the failure of several metabotropic glutamate receptor subtype 5 (mGlur5) selective antagonists under clinical investigation, no clear single treatment appears to be greatly effective. These recent challenges call into question various aspects of clinical study design in FXS. More objective outcome measures are under development and validation. Future trials will likely be aimed at correcting multiple pathways known to be disrupted by the loss of FMRP. This review offers a brief summary of the prevalence, phenotypic characteristics, genetic causes and molecular functions of FMRP in the brain (as these have been extensively reviewed elsewhere), discusses the most recent finding in FXS drug development, and summarizes FXS trials utilizing symptomatic treatment. PMID- 26858242 TI - An evidence-based scale for the antecedents of depressive symptoms in Australian adults. AB - OBJECTIVE: To develop and test a self-reported scale designed to measure the antecedents of depression. METHODS: Participants of the Sustainable Mastery of Innovative Lifelong Exercise (SMILE) Tai Chi program were invited to complete the scale for antecedents of depressive symptoms. The scale included questions regarding events/factors the participants have experienced over the past three months and preceded their depressive symptoms. The reliability of the questions was assessed using the Cronbach's alpha. Principal components analysis was used to examine if there were domains of interest across the scale questions. RESULTS: A total of 126 participants completed the scale. The scale had a good internal consistency (Cronbach's alpha = 0.82). Principal components analysis identified three components (life events, psychosocial problems, and physical/health problems) in the scale and the components detected the root categories of depression in more than 56% of the cases. CONCLUSIONS: This simple self administered scale has proven to provide a reliable measure for the antecedent factors of depression in the SMILE Tai Chi cohort; further validation of the scale in different settings is encouraged. PMID- 26858244 TI - A randomized trial of intravitreal bevacizumab vs. ranibizumab for myopic CNV. PMID- 26858245 TI - Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications. AB - Resistance of the Enterobacteriaceae to antibiotics, especially of the beta lactam type, is increasingly dominated by the mobilization of continuously expressed single genes that encode efficient drug modifying enzymes. Strong and ubiquitous selection pressure has seemingly been accompanied by a shift from "natural" resistance, such as inducible chromosomal enzymes, membrane impermeability, and drug efflux, to the modern paradigm of mobile gene pools that largely determine the epidemiology of modern antibiotic resistance. In this way, antibiotic resistance is more available than ever before to organisms such as Escherichia coli and Klebsiella pneumoniae that are important causes of major sepsis. Modulation of the phenotype by host bacteria makes gene transmission less obvious and may in part explain why tracking and control of carbapenem resistance has been particularly problematic in the Enterobacteriaceae. This review discusses the underlying principles and clinical implications of the mobility and fixation of resistance genes and the exploitable opportunities and potential threats arising from apparent limitations on diversity in these mobile gene pools. It also provides some illustrative paradoxes and clinical corollaries, as well as a summary of future options. PMID- 26858243 TI - Effect of electrical forepaw stimulation on capillary transit-time heterogeneity (CTH). AB - Functional hyperemia reduces oxygen extraction efficacy unless counteracted by a reduction of capillary transit-time heterogeneity of blood. We adapted a bolus tracking approach to capillary transit-time heterogeneity estimation for two photon microscopy and then quantified changes in plasma mean transit time and capillary transit-time heterogeneity during forepaw stimulation in anesthetized mice (C57BL/6NTac). In addition, we analyzed transit time coefficient of variance = capillary transit-time heterogeneity/mean transit time, which we expect to remain constant in passive, compliant microvascular networks. Electrical forepaw stimulation reduced, both mean transit time (11.3% +/- 1.3%) and capillary transit-time heterogeneity (24.1% +/- 3.3%), consistent with earlier literature and model predictions. We observed a coefficient of variance reduction (14.3% +/- 3.5%) during functional activation, especially for the arteriolar-to-venular passage. Such coefficient of variance reduction during functional activation suggests homogenization of capillary flows beyond that expected as a passive response to increased blood flow by other stimuli. This finding is consistent with an active neurocapillary coupling mechanism, for example via pericyte dilation. Mean transit time and capillary transit-time heterogeneity reductions were consistent with the relative change inferred from capillary hemodynamics (cell velocity and flux). Our findings support the important role of capillary transit-time heterogeneity in flow-metabolism coupling during functional activation. PMID- 26858246 TI - Inhibition of the Formation of the Spf1p Phosphoenzyme by Ca2. AB - P5-ATPases are important for processes associated with the endosomal-lysosomal system of eukaryotic cells. In humans, the loss of function of P5-ATPases causes neurodegeneration. In the yeastSaccharomyces cerevisiae, deletion of P5-ATPase Spf1p gives rise to endoplasmic reticulum stress. The reaction cycle of P5 ATPases is poorly characterized. Here, we showed that the formation of the Spf1p catalytic phosphoenzyme was fast in a reaction medium containing ATP, Mg(2+), and EGTA. Low concentrations of Ca(2+)in the phosphorylation medium decreased the rate of phosphorylation and the maximal level of phosphoenzyme. Neither Mn(2+)nor Mg(2+)had an inhibitory effect on the formation of the phosphoenzyme similar to that of Ca(2+) TheKmfor ATP in the phosphorylation reaction was ~1 MUmand did not significantly change in the presence of Ca(2+) Half-maximal phosphorylation was attained at 8 MUmMg(2+), but higher concentrations partially protected from Ca(2+)inhibition. In conditions similar to those used for phosphorylation, Ca(2+)had a small effect accelerating dephosphorylation and minimally affected ATPase activity, suggesting that the formation of the phosphoenzyme was not the limiting step of the ATP hydrolytic cycle. PMID- 26858247 TI - Structure and Functional Properties of the Active Form of the Proteolytic Complex, ClpP1P2, from Mycobacterium tuberculosis. AB - The ClpP protease complex and its regulatory ATPases, ClpC1 and ClpX, inMycobacterium tuberculosis(Mtb) are essential and, therefore, promising drug targets. TheMtbClpP protease consists of two heptameric rings, one composed of ClpP1 and the other of ClpP2 subunits. Formation of the enzymatically active ClpP1P2 complex requires binding of N-blocked dipeptide activators. We have found a new potent activator, benzoyl-leucine-leucine (Bz-LL), that binds with higher affinity and promotes 3-4-fold higher peptidase activity than previous activators. Bz-LL-activated ClpP1P2 specifically stimulates the ATPase activity ofMtbClpC1 and ClpX. The ClpC1P1P2 and ClpXP1P2 complexes exhibit 2-3-fold enhanced ATPase activity, peptide cleavage, and ATP-dependent protein degradation. The crystal structure of ClpP1P2 with bound Bz-LL was determined at a resolution of 3.07 A and with benzyloxycarbonyl-Leu-Leu (Z-LL) bound at 2.9 A. Bz-LL was present in all 14 active sites, whereas Z-LL density was not resolved. Surprisingly, Bz-LL adopts opposite orientations in ClpP1 and ClpP2. In ClpP1, Bz LL binds with the C-terminal leucine side chain in the S1 pocket. One C-terminal oxygen is close to the catalytic serine, whereas the other contacts backbone amides in the oxyanion hole. In ClpP2, Bz-LL binds with the benzoyl group in the S1 pocket, and the peptide hydrogen bonded between parallel beta-strands. The ClpP2 axial loops are extended, forming an open axial channel as has been observed with bound ADEP antibiotics. Thus occupancy of the active sites of ClpP allosterically alters sites on the surfaces thereby affecting the association of ClpP1 and ClpP2 rings, interactions with regulatory ATPases, and entry of protein substrates. PMID- 26858248 TI - Characterization of Neuronal Tau Protein as a Target of Extracellular Signal regulated Kinase. AB - Tau neuronal protein has a central role in neurodegeneration and is implicated in Alzheimer disease development. Abnormal phosphorylation of Tau impairs its interaction with other proteins and is associated with its dysregulation in pathological conditions. Molecular mechanisms leading to hyperphosphorylation of Tau in pathological conditions are unknown. Here, we characterize phosphorylation of Tau by extracellular-regulated kinase (ERK2), a mitogen-activated kinase (MAPK) that responds to extracellular signals. Analysis ofin vitrophosphorylated Tau by activated recombinant ERK2 with nuclear magnetic resonance spectroscopy (NMR) reveals phosphorylation of 15 Ser/Thr sites.In vitrophosphorylation of Tau using rat brain extract and subsequent NMR analysis identifies the same sites. Phosphorylation with rat brain extract is known to transform Tau into an Alzheimer disease-like state. Our results indicate that phosphorylation of Tau by ERK2 alone is sufficient to produce the same characteristics. We further investigate the mechanism of ERK2 phosphorylation of Tau. Kinases are known to recognize their protein substrates not only by their specificity for a targeted Ser or Thr phosphorylation site but also by binding to linear-peptide motifs called docking sites. We identify two main ERK2 docking sites in Tau sequence using NMR. Our results suggest that ERK2 dysregulation in Alzheimer disease could lead to abnormal phosphorylation of Tau resulting in the pathology of the disease. PMID- 26858249 TI - Inhibitor of Differentiation/DNA Binding 1 (ID1) Inhibits Etoposide-induced Apoptosis in a c-Jun/c-Fos-dependent Manner. AB - ID1 (inhibitor of differentiation/DNA binding 1) acts an important role in metastasis, tumorigenesis, and maintenance of cell viability. It has been shown that the up-regulation of ID1 is correlated with poor prognosis and the resistance to chemotherapy of human cancers. However, the underlying molecular mechanism remains elusive. Here, we determined for the first time that up regulating ID1 upon etoposide activation was mediated through AP-1 binding sites within theID1promoter and confirmed that ID1 enhanced cell resistance to DNA damage-induced apoptosis in esophageal squamous cell carcinoma cells. Ablation of c-Jun/c-Fos or ID1 expression enhanced etoposide-mediated apoptosis through increasing activity of caspase 3 and PARP cleavage. Moreover, c-Jun/c-Fos and ID1 were positively correlated in human cancers. More importantly, simultaneous high expression of ID1 and c-Jun or c-Fos was correlated with poor survival in cancer patients. Collectively, we demonstrate the importance of c-Jun/c-Fos-ID1 signaling pathway in chemoresistance of esophageal cancer cells and provide considerable insight into understanding the underlying molecular mechanisms in esophageal squamous cell carcinoma cell biology. PMID- 26858250 TI - The Structure of the Transcriptional Repressor KstR in Complex with CoA Thioester Cholesterol Metabolites Sheds Light on the Regulation of Cholesterol Catabolism in Mycobacterium tuberculosis. AB - Cholesterol can be a major carbon source forMycobacterium tuberculosisduring infection, both at an early stage in the macrophage phagosome and later within the necrotic granuloma. KstR is a highly conserved TetR family transcriptional repressor that regulates a large set of genes responsible for cholesterol catabolism. Many genes in this regulon, includingkstR, are either induced during infection or are essential for survival ofM. tuberculosis in vivo In this study, we identified two ligands for KstR, both of which are CoA thioester cholesterol metabolites with four intact steroid rings. A metabolite in which one of the rings was cleaved was not a ligand. We confirmed the ligand-protein interactions using intrinsic tryptophan fluorescence and showed that ligand binding strongly inhibited KstR-DNA binding using surface plasmon resonance (IC50for ligand = 25 nm). Crystal structures of the ligand-free form of KstR show variability in the position of the DNA-binding domain. In contrast, structures of KstR.ligand complexes are highly similar to each other and demonstrate a position of the DNA binding domain that is unfavorable for DNA binding. Comparison of ligand-bound and ligand-free structures identifies residues involved in ligand specificity and reveals a distinctive mechanism by which the ligand-induced conformational change mediates DNA release. PMID- 26858251 TI - Tuning of Hemes b Equilibrium Redox Potential Is Not Required for Cross-Membrane Electron Transfer. AB - In biological energy conversion, cross-membrane electron transfer often involves an assembly of two hemesb The hemes display a large difference in redox midpoint potentials (DeltaEm_b), which in several proteins is assumed to facilitate cross membrane electron transfer and overcome a barrier of membrane potential. Here we challenge this assumption reporting on hemebligand mutants of cytochromebc1in which, for the first time in transmembrane cytochrome, one natural histidine has been replaced by lysine without loss of the native low spin type of heme iron. With these mutants we show that DeltaEm_b can be markedly increased, and the redox potential of one of the hemes can stay above the level of quinone pool, or DeltaEm_b can be markedly decreased to the point that two hemes are almost isopotential, yet the enzyme retains catalytically competent electron transfer between quinone binding sites and remains functionalin vivo This reveals that cytochromebc1can accommodate large changes in DeltaEm_b without hampering catalysis, as long as these changes do not impose overly endergonic steps on downhill electron transfer from substrate to product. We propose that hemesbin this cytochrome and in other membranous cytochromesbact as electronic connectors for the catalytic sites with no fine tuning in DeltaEm_b required for efficient cross-membrane electron transfer. We link this concept with a natural flexibility in occurrence of several thermodynamic configurations of the direction of electron flow and the direction of the gradient of potential in relation to the vector of the electric membrane potential. PMID- 26858252 TI - Structural and Functional Analysis of a Lytic Polysaccharide Monooxygenase Important for Efficient Utilization of Chitin in Cellvibrio japonicus. AB - Cellvibrio japonicusis a Gram-negative soil bacterium that is primarily known for its ability to degrade plant cell wall polysaccharides through utilization of an extensive repertoire of carbohydrate-active enzymes. Several putative chitin degrading enzymes are also found among these carbohydrate-active enzymes, such as chitinases, chitobiases, and lytic polysaccharide monooxygenases (LPMOs). In this study, we have characterized the chitin-active LPMO,CjLPMO10A, a tri-modular enzyme containing a catalytic family AA10 LPMO module, a family 5 chitin-binding module, and a C-terminal unclassified module of unknown function. Characterization of the latter module revealed tight and specific binding to chitin, thereby unraveling a new family of chitin-binding modules (classified as CBM73). X-ray crystallographic elucidation of theCjLPMO10A catalytic module revealed that the active site of the enzyme combines structural features previously only observed in either cellulose or chitin-active LPMO10s. Analysis of the copper-binding site by EPR showed a signal signature more similar to those observed for cellulose-cleaving LPMOs. The full-length LPMO shows no activity toward cellulose but is able to bind and cleave both alpha- and beta-chitin. Removal of the chitin-binding modules reduced LPMO activity toward alpha-chitin compared with the full-length enzyme. Interestingly, the full-length enzyme and the individual catalytic LPMO module boosted the activity of an endochitinase equally well, also yielding similar amounts of oxidized products. Finally, gene deletion studies show thatCjLPMO10A is needed byC. japonicusto obtain efficient growth on both purified chitin and crab shell particles. PMID- 26858253 TI - Cytokines Regulate beta-Cell Thioredoxin-interacting Protein (TXNIP) via Distinct Mechanisms and Pathways. AB - Thioredoxin-interacting protein (TXNIP) is a key regulator of diabetic beta-cell apoptosis and dysfunction, and TXNIP inhibition prevents diabetes in mouse models of type 1 and type 2 diabetes. Although we have previously shown that TXNIP is strongly induced by glucose, any regulation by the proinflammatory cytokines tumor necrosis factor alpha (TNFalpha), interleukin-1beta (IL-1beta), and interferon gamma (IFNgamma) has remained largely unexplored. Moreover, even though this three-cytokine mixture is widely used to mimic type 1 diabetes in vitro, the mechanisms involved are not fully understood. Interestingly, we have now found that this cytokine mixture increases beta-cell TXNIP expression; however, although TNFalpha had no effect, IL-1beta surprisingly down-regulated TXNIP transcription, whereas IFNgamma increased TXNIP levels in INS-1 beta-cells and primary islets. Human TXNIP promoter analyses and chromatin immunoprecipitation studies revealed that the IL-1beta effect was mediated by inhibition of carbohydrate response element binding protein activity. In contrast, IFNgamma increased pro-apoptotic TXNIP post-transcriptionally via induction of endoplasmic reticulum stress, activation of inositol-requiring enzyme 1alpha (IRE1alpha), and suppression of miR-17, a microRNA that targets and down-regulates TXNIP. In fact, miR-17 knockdown was able to mimic the IFNgamma effects on TXNIP, whereas miR-17 overexpression blunted the cytokine effect. Thus, our results demonstrate for the first time that the proinflammatory cytokines TNFalpha, IL-1beta, and IFNgamma each have distinct and in part opposing effects on beta-cell TXNIP expression. These findings thereby provide new mechanistic insight into the regulation of TXNIP and beta-cell biology and reveal novel links between proinflammatory cytokines, carbohydrate response element binding protein-mediated transcription, and microRNA signaling. PMID- 26858256 TI - Non-lysosomal Degradation of Singly Phosphorylated Oligosaccharides Initiated by the Action of a Cytosolic Endo-beta-N-acetylglucosaminidase. AB - Phosphorylated oligosaccharides (POSs) are produced by the degradation of dolichol-linked oligosaccharides (DLOs) by an unclarified mechanism in mammalian cells. Although POSs are exclusively found in the cytosol, their intracellular fates remain unclear. Our findings indicate that POSs are catabolized via a non lysosomal glycan degradation pathway that involves a cytosolic endo-beta-N acetylglucosaminidase (ENGase). Quantitative and structural analyses of POSs revealed that ablation of the ENGase results in the significant accumulation of POSs with a hexasaccharide structure composed of Manalpha1,2Manalpha1,3(Manalpha1,6)Manbeta1,4GlcNAcbeta1,4GlcNAc.In vitroENGase assays revealed that the presence of an alpha1,2-linked mannose residue facilitates the hydrolysis of POSs by the ENGase. Liquid chromatography-mass spectrometric analyses and fluorescent labeling experiments show that such POSs contain one phosphate group at the reducing end. These results indicate that ENGase efficiently hydrolyzes POSs that are larger than Man4GlcNAc2-P, generating GlcNAc-1-P and neutral Gn1-type free oligosaccharides. These results provide insight into important aspects of the generation and degradation of POSs. PMID- 26858255 TI - Central Role of Pyruvate Kinase in Carbon Co-catabolism of Mycobacterium tuberculosis. AB - Mycobacterium tuberculosis (Mtb) displays a high degree of metabolic plasticity to adapt to challenging host environments. Genetic evidence suggests thatMtbrelies mainly on fatty acid catabolism in the host. However,Mtbalso maintains a functional glycolytic pathway and its role in the cellular metabolism ofMtbhas yet to be understood. Pyruvate kinase catalyzes the last and rate limiting step in glycolysis and theMtbgenome harbors one putative pyruvate kinase (pykA, Rv1617). Here we show thatpykAencodes an active pyruvate kinase that is allosterically activated by glucose 6-phosphate (Glc-6-P) and adenosine monophosphate (AMP). Deletion ofpykApreventsMtbgrowth in the presence of fermentable carbon sources and has a cidal effect in the presence of glucose that correlates with elevated levels of the toxic catabolite methylglyoxal. Growth attenuation was also observed in media containing a combination of short chain fatty acids and glucose and surprisingly, in media containing odd and even chain fatty acids alone. Untargeted high sensitivity metabolomics revealed that inactivation of pyruvate kinase leads to accumulation of phosphoenolpyruvate (P enolpyruvate), citrate, and aconitate, which was consistent with allosteric inhibition of isocitrate dehydrogenase by P-enolpyruvate. This metabolic block could be relieved by addition of the alpha-ketoglutarate precursor glutamate. Taken together, our study identifies an essential role of pyruvate kinase in preventing metabolic block during carbon co-catabolism inMtb. PMID- 26858257 TI - Meta-Prediction of MTHFR Gene Polymorphism Mutations and Associated Risk for Colorectal Cancer. AB - The methylenetetrahydrofolate reductase (MTHFR) gene is one of the most investigated of the genes associated with chronic human diseases because of its associations with hyperhomocysteinemia and toxicity. It has been proposed as a prototype gene for the prevention of colorectal cancer (CRC). The major objectives of this meta-analysis were to examine the polymorphism-mutation patterns of MTHFR and their associations with risk for CRC as well as potential contributing factors for mutations and disease risks. This analysis included 33,626 CRC cases and 48,688 controls across 92 studies for MTHFR 677 and 16,367 cases and 24,874 controls across 54 studies for MTHFR 1298, comprising data for various racial and ethnic groups, both genders, and multiple cancer sites. MTHFR 677 homozygous TT genotype was protective (p <05) for CRC for all included populations; however, with heterogeneity across various racial-ethnic groups and opposing findings, it was a risk genotype for the subgroup of Hispanics (p <01). Additional countries for which subgroup analyses resulted in 677 TT as a risk genotype included Turkey, Romania, Croatia, Hungary, Portugal, Mexico, Brazil, U.S. Hawai'i, Taiwan, India, and Egypt. Countries with the highest mutation rates and risks for both MTHFR 677 and 1298 genotypes are presented using global maps to visualize the grouping patterns. Meta-predictive analyses revealed that air pollution levels were associated with gene polymorphisms for both genotypes. Future nursing research should be conducted to develop proactive measures to protect populations in cities where air pollution causes more deaths. PMID- 26858254 TI - Degradation of the Separase-cleaved Rec8, a Meiotic Cohesin Subunit, by the N-end Rule Pathway. AB - The Ate1 arginyltransferase (R-transferase) is a component of the N-end rule pathway, which recognizes proteins containing N-terminal degradation signals called N-degrons, polyubiquitylates these proteins, and thereby causes their degradation by the proteasome. Ate1 arginylates N-terminal Asp, Glu, or (oxidized) Cys. The resulting N-terminal Arg is recognized by ubiquitin ligases of the N-end rule pathway. In the yeastSaccharomyces cerevisiae, the separase mediated cleavage of the Scc1/Rad21/Mcd1 cohesin subunit generates a C-terminal fragment that bears N-terminal Arg and is destroyed by the N-end rule pathway without a requirement for arginylation. In contrast, the separase-mediated cleavage of Rec8, the mammalian meiotic cohesin subunit, yields a fragment bearing N-terminal Glu, a substrate of the Ate1 R-transferase. Here we constructed and used a germ cell-confinedAte1(-/-)mouse strain to analyze the separase-generated C-terminal fragment of Rec8. We show that this fragment is a short-lived N-end rule substrate, that its degradation requires N-terminal arginylation, and that maleAte1(-/-)mice are nearly infertile, due to massive apoptotic death ofAte1(-/-)spermatocytes during the metaphase of meiosis I. These effects ofAte1ablation are inferred to be caused, at least in part, by the failure to destroy the C-terminal fragment of Rec8 in the absence of N-terminal arginylation. PMID- 26858258 TI - Clinical, pathological, immunohistochemical and molecular characterization of feline chronic gingivostomatitis. AB - Objectives This study presents the clinical, pathological, immunohistochemical and molecular characterization of 26 cats with feline chronic gingivostomatitis (FCG). Methods Oral mucosal biopsies, blood and swabs were collected from cats presenting with oral lesions. The tissue sections were submitted for histopathology and immunohistochemical analysis for feline calicivirus (FCV), feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV). The swabs were subjected to PCR analysis for FCV, and blood for FeLV and FIV. Results The main clinical findings were dysphagia (88.2%), halitosis (76.5%), sialorrhea (47.1%), weight loss (41.2%), intense oral discomfort (35.3%), oral hemorrhage (17.6%), and lackluster and fragile coat (11.8%). Gross inspection revealed bilateral lesions across the palatoglossal fold to the lateral tongue base. The lesions were diffuse, proliferative, intensely red and friable, and bled easily upon examination in 80.8% of cases. In 23.1% of cases, the lesions were multifocal to coalescent, at times forming multiple vesicles on a reddened, edematous palatoglossal fold. Microscopic examination showed that 15.4% of lesions had moderate (grade 2) and 84.6% had severe (grade 3) inflammation. Immunohistochemistry revealed the presence of FeLV antigens in the epithelium and the inflammatory infiltrate of 30.8% of the cats with FCG. FCV antigens were not detected in the FCG lesions. Conclusions and relevance The FCG cases analyzed could not be correlated with FCV. It is possible that FeLV plays a role as a causal agent of lesions in cases where the presence of the virus has been confirmed by immunohistochemistry in epithelial samples. PMID- 26858259 TI - CDC updates Zika virus guidance to protect pregnant women. PMID- 26858260 TI - The phenotype of migraine with unilateral cranial autonomic symptoms documents increased peripheral and central trigeminal sensitization. A case series of 757 patients. AB - BACKGROUND: Migraine with unilateral cranial autonomic symptoms (UAS) is a putative migraine endophenotype with convincing response to trigeminal-targeted treatments that still needs a thorough characterization. OBJECTIVE: The objective of this article is to carefully investigate the clinical phenotype of migraine with UAS in a large group of patients for more accurate migraine diagnoses, improved clinical management, and better outcome prediction. METHODS: We studied 757 consecutive episodic and chronic migraineurs in a tertiary headache clinic with face-to-face interviews, detailing in depth their lifestyle, sociodemographic and headache characteristics. RESULTS: Migraineurs with UAS (37.4%) differed from the general migraine population with respect to longer attack duration (OR = 2.47, p < 0.02, having >72-hour long attacks), more strictly unilateral (OR = 3.18, p < 0.001) and severe headache (OR = 1.72, p = 0.011), more frequent allodynia (OR = 3.03, p < 0.001) and photophobia (OR = 1.87, p = 0.019). CONCLUSIONS: Migraine patients with UAS are characterized not only by symptoms due to intense peripheral trigeminal activation but also to central sensitization. Our study broadens the knowledge on the clinical and phenotypic characteristics of migraine with UAS, suggests pathophysiological implications, and supports the need for future prospective clinical studies. PMID- 26858261 TI - Judge might reopen GSK paroxetine case. PMID- 26858262 TI - Handing Off Safety at the Bedside. AB - The study purpose was to describe how bedside nurses can use nursing bedside shift report (NBSR) to keep patients safe. NBSR has been recommended as a means of increasing patient safety, but little is known about how or whether it does so. Grounded theory methods were used. Data were collected from 2014 to 2015 with bedside nurses in a pediatric unit with an established NBSR process. The primary process by which bedside nurses use NBSR to keep patients safe is reducing risk of harm through conveying the patient story from shift to shift. Having a perspective from the bedside is a key antecedent to reducing risk of harm, as it supports the nurses' ability to subsequently identify and address risks. Although often seen as a routine exchange of information, how nursing shift report is conducted can impact patient safety. The study reinforces the value of targeting nursing communication to improve patient safety. PMID- 26858263 TI - David Oliver: Jeremy Hunt was wrong to blame the "irresponsible BMA" for his own mistakes. PMID- 26858264 TI - Muscle-on-chip: An in vitro model for donor-host cardiomyocyte coupling. AB - A key aspect of cardiac cell-based therapy is the proper integration of newly formed cardiomyocytes into the remnant myocardium after injury. In this issue, Aratyn-Schaus et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201508026) describe an in vitro model for heterogeneous cardiomyocyte coupling in which force transmission between cells can be measured. PMID- 26858265 TI - Plakophilin-2 loss promotes TGF-beta1/p38 MAPK-dependent fibrotic gene expression in cardiomyocytes. AB - Members of the desmosome protein family are integral components of the cardiac area composita, a mixed junctional complex responsible for electromechanical coupling between cardiomyocytes. In this study, we provide evidence that loss of the desmosomal armadillo protein Plakophilin-2 (PKP2) in cardiomyocytes elevates transforming growth factor beta1 (TGF-beta1) and p38 mitogen-activated protein kinase (MAPK) signaling, which together coordinate a transcriptional program that results in increased expression of profibrotic genes. Importantly, we demonstrate that expression of Desmoplakin (DP) is lost upon PKP2 knockdown and that restoration of DP expression rescues the activation of this TGF-beta1/p38 MAPK transcriptional cascade. Tissues from PKP2 heterozygous and DP conditional knockout mouse models also exhibit elevated TGF-beta1/p38 MAPK signaling and induction of fibrotic gene expression in vivo. These data therefore identify PKP2 and DP as central players in coordination of desmosome-dependent TGF-beta1/p38 MAPK signaling in cardiomyocytes, pathways known to play a role in different types of cardiac disease, such as arrhythmogenic or hypertrophic cardiomyopathy. PMID- 26858266 TI - Coupling primary and stem cell-derived cardiomyocytes in an in vitro model of cardiac cell therapy. AB - The efficacy of cardiac cell therapy depends on the integration of existing and newly formed cardiomyocytes. Here, we developed a minimal in vitro model of this interface by engineering two cell microtissues (MUtissues) containing mouse cardiomyocytes, representing spared myocardium after injury, and cardiomyocytes generated from embryonic and induced pluripotent stem cells, to model newly formed cells. We demonstrated that weaker stem cell-derived myocytes coupled with stronger myocytes to support synchronous contraction, but this arrangement required focal adhesion-like structures near the cell-cell junction that degrade force transmission between cells. Moreover, we developed a computational model of MUtissue mechanics to demonstrate that a reduction in isometric tension is sufficient to impair force transmission across the cell-cell boundary. Together, our in vitro and in silico results suggest that mechanotransductive mechanisms may contribute to the modest functional benefits observed in cell-therapy studies by regulating the amount of contractile force effectively transmitted at the junction between newly formed and spared myocytes. PMID- 26858268 TI - The prevalence and preventive measures of the respiratory illness among Malaysian pilgrims in 2013 Hajj season. AB - BACKGROUND: Respiratory illness continues to exert a burden on hajj pilgrims in Makkah. The purpose of this study is to determine the prevalence of respiratory illness and its associated factors among Malaysian hajj pilgrims in 2013 and to describe its preventive measures. METHODS: A cross-sectional study was conducted in Makkah and Malaysia during the 2013 hajj season. A self-administered proforma on social demographics, previous experience of hajj or umrah, smoking habits, co morbid illness and practices of preventive measures against respiratory illness were obtained. RESULTS: A total of 468 proforma were analysed. The prevalence of the respiratory illness was 93.4% with a subset of 78.2% fulfilled the criteria for influenza-like illness (ILI). Most of them (77.8%) had a respiratory illness of <2 weeks duration. Approximately 61.8% were administered antibiotics but only 2.1% of them had been hospitalized. Most of them acquired the infection after a brief stay at Arafat (81.2%). Vaccination coverages for influenza virus and pneumococcal disease were quite high, 65.2% and 59.4%, respectively. For other preventive measures practices, only 31.8% of them practiced good hand hygiene, ~82.9% of pilgrims used surgical face masks, N95 face masks, dry towels, wet towels or veils as their face masks. Nearly one-half of the respondents (44.4%) took vitamins as their food supplement. Malaysian hajj pilgrims with previous experience of hajj (OR 0.24; 95% CI 0.10-0.56) or umrah (OR 0.19; 95% CI 0.07 0.52) and those who have practiced good hand hygiene (OR 0.35; 95% CI 0.16-0.79) were found to be significantly associated with lower risk of having respiratory illness. Otherwise, pilgrims who had contact with those with respiratory illness (OR 2.61; 95% CI 1.12-6.09) was associated with higher risk. CONCLUSIONS: The prevalence of respiratory illness remains high among Malaysian hajj pilgrims despite having some practices of preventive measures. All preventive measures which include hand hygiene, wearing face masks and influenza vaccination must be practiced together as bundle of care to reduce respiratory illness effectively. PMID- 26858269 TI - Analysis of delayed TBE-vaccine booster after primary vaccination. AB - An open, uncontrolled single centre study was conducted in the Travel Clinic at the Military Hospital, Brussels. Eighty-eight subjects were recruited who had a primary series of tick-borne encephalitis (TBE) vaccine more than 5 years ago and who never received a booster dose afterwards. Response rate after booster vaccination was very high: 84 out of 88 subjects (95.5%) had neutralizing antibodies on plaque reduction neutralization test and all (100%) had IgG antibodies on ELISA, on Day 21-28 after booster vaccination. This study adds valuable information to the common situation of delayed booster interval. The results of our study indicate that in young healthy travellers (<50 years), one booster vaccination after a primary series of TBE vaccine in the past is sufficient to obtain protective antibodies, even if primary vaccination is much longer than the recommended booster interval of 5 years. PMID- 26858267 TI - Metabolic regulation of mitochondrial dynamics. AB - Mitochondria are renowned for their central bioenergetic role in eukaryotic cells, where they act as powerhouses to generate adenosine triphosphate from oxidation of nutrients. At the same time, these organelles are highly dynamic and undergo fusion, fission, transport, and degradation. Each of these dynamic processes is critical for maintaining a healthy mitochondrial population. Given the central metabolic function of mitochondria, it is not surprising that mitochondrial dynamics and bioenergetics reciprocally influence each other. We review the dynamic properties of mitochondria, with an emphasis on how these processes respond to cellular signaling events and how they affect metabolism. PMID- 26858270 TI - Prolonged incubation period of Hookworm-related cutaneous larva migrans. PMID- 26858271 TI - Marine envenomations in returning French travellers seen in a tropical diseases unit, 2008-13. AB - BACKGROUND: Travel and aquatic activities are increasing in tropical regions. The risk and the spectrum of marine envenomation are unknown in travellers. This work aims to evaluate the prevalence and the characteristics of marine envenomations in returning travellers. METHODS: We retrospectively studied the medical charts of all returning travellers presenting with a health problem in a French tropical disease unit between 2008 and 2013, with focus on travellers complaining of marine envenomation. Characteristics of each type of envenomation are described. RESULTS: Of the 3315 travellers seen during the study period, 43 consulted for a presumed marine envenomation. Six patients were excluded, leaving 37 cases of confirmed marine envenomation. It corresponds to a prevalence of 1.1%. Sex ratio was balanced with 18 men and 19 women. Median age was 42 years (range 25-68 years). Median travel duration was 14 days (range: 6-62 days). The main travel destination was Southeast Asia in 10 cases, followed by islands of East Africa in seven cases. Median elapsed time between envenomation and consultation was 14 days (range: 2-130 days). The purpose of travel was tourism in all cases. The main clinical aspects were oedema, sting marks, cellulitis and flagellations. Eleven cases were presumably caused by corals, 10 by stonefish, 8 by jellyfish, 2 by weever fish, 2 by starfish, 2 by stingray, 1 by lionfish and 1 by sea anemone. CONCLUSION: Prevalence of marine envenomation is low in returning travellers. They are mostly caused by corals, stonefish and jellyfish. PMID- 26858272 TI - High carriage rate of ESBL-producing Enterobacteriaceae at presentation and follow-up among travellers with gastrointestinal complaints returning from India and Southeast Asia. AB - BACKGROUND: International travel contributes to the spread of multidrug-resistant microorganisms including extended spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). We assessed the proportion of faecal carriers of ESBL-PE among 211 patients with gastrointestinal symptoms who returned to Berlin, Germany, after international travel. METHODS: ESBL-PE were screened for on chromogenic agar, antimicrobial susceptibility testing was performed, and ESBL genes were genotyped. Travel-related data were assessed by questionnaire. RESULTS: Diarrhoea, abdominal pain and nausea were the main symptoms. Half of the travellers carried ESBL-PE (97% Escherichia coli); the proportion was highest for returnees from India (72%) and mainland Southeast Asia (59%), and comparatively lower for Africa (33%) and Central America (20%). Co-resistance to fluoroquinolones (particularly in isolates from India), gentamicin and cotrimoxazole was frequent but all isolates were carbapenem-susceptible. ESBL-PE carriage decreased with increasing timespan from return to presentation, and with age. At revisit of initially ESBL-PE positive patients half a year later, 28% (17/61) of the individuals were still carriers, CTX-M groups being congruent with the initial isolates. CTX-M groups 9 and 1/9, vegetarian diet and cat ownership tended to be associated with ESBL-PE carriage upon revisit. CONCLUSIONS: Travellers, particularly those returning from India and Southeast Asia, constitute a relevant source of potential spread of ESBL-PE. Carriage declines over time but ESBL-PE persist for at least 6 months in a substantial proportion of individuals. Both genetic characteristics of the bacteria and lifestyle factors seem to contribute to persistent carriage of ESBL-PE. A recent, extra European travel history argues for ESBL-PE screening and contact precautions for patients admitted to hospital. PMID- 26858273 TI - Rash caused by Oryctes nasicornis. AB - We report a case of rash caused by crushing of a male of Oryctes nasicornis (Linnaeus 1758) (Coleoptera, "http:// it. wikipedia. org/ wiki/ Scarabaeidae" ?o "Scarabaeidae" Scarabaeidae), popularly known as "European rhinoceros beetle", on the skin of an Italian tourist who developed the reaction during a trip to Turkey. The rash appeared one hour after the crushing of the insect on the skin. The patient was observed one day later, when she returned to Italy. To our knowledge, no similar cases have been reported in the literature. PMID- 26858274 TI - The 'selfie' phenomenon: reducing the risk of harm while using smartphones during international travel. AB - BACKGROUND: Photography is an integral component of the international travel experience. Self-photography is becoming a mainstream behaviour in society and it has implications for the practice of travel medicine. Travellers who take selfies, including with the use of selfie sticks, may be subject to traumatic injuries associated with this activity. This review article is the first in the medical literature to address this emerging phenomenon. METHODS: Articles indexed on PubMed and Scopus databases through 2015 were retrieved, using the search terms 'travel', combined with 'selfie', 'self-photography', 'smartphone', 'mobile phone' and 'social media'. The reference lists of articles were manually searched for additional publications, and published media reports of travel-related self photography were examined. RESULTS: The lack of situational awareness and temporary distraction inherent in selfie-taking exposes the traveller to potential hazards. A diverse group of selfie injuries has been reported, including injury and death secondary to selfie-related falls, attacks from wild animals, electrocution, lightning strikes, trauma at sporting events, road traffic and pedestrian accidents. Public health measures adopted by the Russian Federation in response to over 100 reported selfie injuries in 2015 alone are presented. The review also discusses the potential for direct trauma from the use of selfie sticks. Travel-related scenarios where selfies should be avoided include photographs taken from a height, on a bridge, in the vicinity of vehicular traffic, during thunderstorms, at sporting events, and where wild animals are in the background. Recommendations exist which discourage use of mobile phones in drivers and pedestrians. CONCLUSIONS: The travel medicine practitioner should routinely counsel travellers about responsible self photography during international travel and should include this advice in printed material given to the patient. The travel and mobile phone industries should reinforce these health promotion messages. Future research should offer greater insights into traveller selfie-taking behaviour. PMID- 26858275 TI - First report of Entamoeba histolytica infection from Timor-Leste--acute amoebic colitis and concurrent late development of amoebic liver abscess in returned travellers to Australia. AB - This communication reports invasive amoebic colitis and late onset amoebic liver abscess in three members of a group of 12 Australian travellers to Timor-Leste (TL). This is the first report of Entamoeba histolytica infection from TL. Clinicians in Australia need to consider amoebiasis in the differential diagnosis in travellers returning with colitis, abdominal pain and fever. Presentation with amoebic liver abscess months after exposure is rare but should be suspected in symptomatic individuals with a relevant history of travel. PMID- 26858276 TI - Azithromycin and ceftriaxone combination treatment for relapsed Salmonella Paratyphi A bacteraemia. PMID- 26858278 TI - Impact of prolonged walking exercise on cardiac structure and function in cardiac patients versus healthy controls. AB - BACKGROUND AND DESIGN: Previous studies have demonstrated that endurance exercise can cause an acute transient decrease in cardiac function in healthy subjects. Whether this also occurs in cardiac patients is unknown. We investigated the impact of prolonged single day and three-day walking exercise on cardiac function and cardiac biomarkers between cardiac patients and healthy controls in an observational study. METHODS: We recruited 10 cardiac patients (nine males, one female, 68 +/- 5 years) and 10 age- and sex-matched healthy control subjects (nine males, one female, 68 +/- 4 years) to perform 30 or 40 km of walking exercise per day for three consecutive days. Cardiac function was examined using echocardiography and cardiac biomarkers (cardiac troponin and B-type natriuretic peptide) with blood samples. Data were collected before walking and directly after walking on day 1 and day 3. RESULTS: Post-exercise early systolic tissue contraction velocity of the left ventricle (p = 0.005) and global longitudinal left ventricle strain (P = 0.026) were increased in both groups compared with baseline. Post-exercise right ventricle peak early diastolic tissue filling velocity and systolic blood pressure/left ventricle end-systolic volume ratio decreased in both groups (p = 0.043 and p = 0.028, respectively). Post-exercise cardiac troponin levels increased (p = 0.045) but did not differ across groups (p = 0.60), whereas B-type natriuretic peptide levels did not change (p = 0.43). CONCLUSION: This study suggests that stable cardiac patients are capable of performing three days of prolonged walking exercise without clinically significant acute overall deterioration in cardiac function or more pronounced increase in cardiac biomarkers compared with healthy controls. PMID- 26858279 TI - The long-term effects of a randomized trial comparing aerobic interval versus continuous training in coronary artery disease patients: 1-year data from the SAINTEX-CAD study. AB - BACKGROUND: Aerobic interval training (AIT) and aerobic continuous training (ACT) both improve physical fitness (peak VO2) in coronary artery disease patients. However, little is known about the long-term effects of AIT and ACT on peak VO2 and exercise adherence. DESIGN: This study is a randomized clinical multicenter trial. METHODS: In total, 163 patients were assessed after 12 weeks of AIT or ACT and 12 months after their enrollment. Physical fitness and physical activity measures served as the primary outcomes, and peripheral endothelial function, cardiovascular risk factors and quality of life (QoL) served as the secondary outcomes. RESULTS: Twenty-six patients dropped out during the intervention; 11 were lost during the follow-up period. Dropouts (n = 37) consisted of more women (p = 0.001) compared to completers (n = 163). Physical fitness (VO2, heart rate and workload at peak and at thresholds) and physical activity (steps, active energy expenditure [kcal], physical activity duration [minutes]) were preserved at the 1-year follow-up (p-time > 0.05) after both AIT and ACT (p-interaction > 0.05). Forty percent of patients showed increased peak VO2, 52% showed increased active energy expenditure and 91.2% met the recommended levels of 150 minutes/week of moderate physical activity (p-group > 0.05). Further, peripheral endothelial function, QoL and cardiovascular risk factors, except systolic blood pressure (p-time < 0.05), remained stable (p-time > 0.05) after both AIT and ACT (p-interaction > 0.05). CONCLUSION: The short-term improvements of center-based AIT and ACT on physical fitness, physical activity, peripheral endothelial function, cardiovascular risk factors and QoL are sustained after a 1-year follow up period. The majority of patients (>90%) met the recommended physical activity levels of 150 minutes/week. PMID- 26858277 TI - Agreement of treatment effects for mortality from routinely collected data and subsequent randomized trials: meta-epidemiological survey. AB - OBJECTIVE: To assess differences in estimated treatment effects for mortality between observational studies with routinely collected health data (RCD; that are published before trials are available) and subsequent evidence from randomized controlled trials on the same clinical question. DESIGN: Meta-epidemiological survey. DATA SOURCES: PubMed searched up to November 2014. METHODS: Eligible RCD studies were published up to 2010 that used propensity scores to address confounding bias and reported comparative effects of interventions for mortality. The analysis included only RCD studies conducted before any trial was published on the same topic. The direction of treatment effects, confidence intervals, and effect sizes (odds ratios) were compared between RCD studies and randomized controlled trials. The relative odds ratio (that is, the summary odds ratio of trial(s) divided by the RCD study estimate) and the summary relative odds ratio were calculated across all pairs of RCD studies and trials. A summary relative odds ratio greater than one indicates that RCD studies gave more favorable mortality results. RESULTS: The evaluation included 16 eligible RCD studies, and 36 subsequent published randomized controlled trials investigating the same clinical questions (with 17,275 patients and 835 deaths). Trials were published a median of three years after the corresponding RCD study. For five (31%) of the 16 clinical questions, the direction of treatment effects differed between RCD studies and trials. Confidence intervals in nine (56%) RCD studies did not include the RCT effect estimate. Overall, RCD studies showed significantly more favorable mortality estimates by 31% than subsequent trials (summary relative odds ratio 1.31 (95% confidence interval 1.03 to 1.65; I(2)=0%)). CONCLUSIONS: Studies of routinely collected health data could give different answers from subsequent randomized controlled trials on the same clinical questions, and may substantially overestimate treatment effects. Caution is needed to prevent misguided clinical decision making. PMID- 26858280 TI - Gross examination and reporting of soft tissue tumours: evaluation of compliance with the UK Royal College of Pathologists soft tissue sarcoma dataset. AB - AIMS: Soft tissue tumours are a heterogeneous group of neoplasms that can arise at almost every anatomical site. As they often show similar clinical and radiological findings, histology is the definitive diagnostic method and it is crucial that the surgical pathology report contains accurate, useful information for management and prognostication. The soft tissue sarcoma minimum dataset produced by the Royal College of Pathologists in the UK outlines a structure for handling and reporting soft tissue tumours, including the core data required, and aiding pathologists in forming a consistent reporting approach. METHODS: We assessed the information in surgical pathology reports for soft tissue lesions at a tertiary soft tissue centre, in 1 year prior to the development of this dataset, and 1 year after its release, to audit the comparative adequacy of macroscopic and microscopic information provided, and to assess for differences in reporting since the advent of routine ancillary molecular diagnostic testing. RESULTS AND CONCLUSIONS: We found that while essential information was always included in reports, more specific details contributing to better quality reports such as more detailed macroscopic descriptions and a higher proportion of clinical summaries with radiological correlation were included in 2011 than 2006, despite increasing workload. Specimen handling, particularly of core biopsies, was also improved, reflecting the increasing need to conserve the maximum amount of patient material for molecular investigations. PMID- 26858281 TI - The Petal-Specific InMYB1 Promoter Functions by Recognizing Petaloid Cells. AB - The InMYB1 gene in Japanese morning glory (Ipomoea nil) is a member of the MYB transcription factor family. The promoter of InMYB1 has been reported to induce petal-specific gene expression in Arabidopsis and Eustoma, and has the same function in several other dicotyledonous plants. Most flowers consist of sepals, petals, stamens and a carpel, whose identity establishment is explained by the ABC model. The establishment of the identity of petals is determined by the expression of class A and B genes in whorl 2. The aim of this study was to clarify whether the InMYB1 promoter functions by recognizing whorl position or petal identity by examining its activity in various mutant and transgenic Arabidopsis thaliana plants in which genes related to the ABC model have been modified. In plants defective in class C gene function, the InMYB1 promoter functioned not only in petals generated in whorl 2 but also in petaloid organs generated in whorl 3; while in the plants defective in class B gene function, the InMYB1 promoter did not function in the sepaloid organs generated in whorl 2. Plants overexpressing class A, B and E genes set flowers with petaloid sepals in whorl 1, i.e. the lateral parts were white and looked like petals, while the central parts were green and looked like sepals. The InMYB1 promoter functioned in the lateral white parts but not in the central green parts. These results show that the InMYB1 promoter functions by recognizing petal identity at the cellular level rather than the whorl position. The petal-specific function of the InMYB1 promoter could be used as a marker to identify petaloid cells. PMID- 26858282 TI - Identification and Functional Characterization of Sesquiterpene Synthases from Xanthium strumarium. AB - Xanthium strumarium synthesizes various pharmacologically active sesquiterpenes. The molecular characterization of sesquiterpene biosynthesis in X. strumarium has not been reported so far. In this study, the cDNAs coding for three sesquiterpene synthases (designated as XsTPS1, XsTPS2 and XsTPS3) were isolated using the X. strumarium transcriptome that we recently constructed. XsTPS1, XsTPS2 and XsTPS3 were revealed to have primary activities forming germacrene D, guaia-4,6-diene and germacrene A, respectively, by either ectopic expression in yeast cells or purified recombinant protein-based in vitro assays. Quantitative real-time PCRs and metabolite analysis for the different plant parts showed that the transcript abundance of XsTPS1-XsTPS3 is consistent with the accumulation pattern of their enzymatic products, supporting their biochemical functions in vivo. In particular, we discovered that none of the XsTPS2 product, guaia-4,6-diene, can be detected in one of the X. strumarium cultivars used in this study (it was named the Hubei-cultivar), in which a natural deletion of two A bases in the XsTPS2 cDNA disrupts its activity, which further confirmed the proposed biochemical role of XsTPS2 in X. strumarium in vivo. PMID- 26858283 TI - The VviMYB80 Gene is Abnormally Expressed in Vitis vinifera L. cv. 'Zhong Shan Hong' and its Expression in Tobacco Driven by the 35S Promoter Causes Male Sterility. AB - Anther development is a very precise and complicated process. In Arabidopsis, the AtMYB80 transcription factor regulates genes involved in pollen development and controls the timing of tapetal programmed cell death (PCD). In this study, we isolated and characterized cDNA for VviMYB80 expressed in flower buds of male sterile Vitis vinifera L. cv. 'Zhong Shan Hong', a late-maturing cultivar derived from self-progeny of cv. 'Wink'. VviMYB80 belongs to the MYB80 subfamily and clusters with AtMYB35/TDF1 in a distinct clade. We found that in flower buds, expression of the VviMYB80 gene in cv. 'Zhong Shan Hong' sharply increased at the tetrad stage, resulting in a higher and earlier transcript level than that found in cv. 'Wink'. Expression of the VviMYB80 gene, driven by the 35S promoter, caused pleiotropic effects on the stamens, including smaller and shriveled anthers, delayed dehiscence, fewer seeds, shorter anther filaments, distorted pollen shape and a lack of cytoplasm, with the tapetum exhibiting hypertrophy in transformed tobacco. These results suggest that VviMYB80 may play an important role in stamen development and that expression of VviMYB80 driven by the 35S promoter in tobacco induces male sterility. PMID- 26858284 TI - CsNIP2;1 is a Plasma Membrane Transporter from Cucumis sativus that Facilitates Urea Uptake When Expressed in Saccharomyces cerevisiae and Arabidopsis thaliana. AB - Urea is an important source of nitrogen (N) for the growth and development of plants. It occurs naturally in soils, is the major N source in agricultural fertilizers and is an important N metabolite in plants. Therefore, the identification and characterization of urea transporters in higher plants is important for the fundamental understanding of urea-based N nutrition in plants and for designing novel strategies for improving the N-use efficiency of urea based-fertilizers. Progress in this area, however, is hampered due to scarce knowledge of plant urea transporters. From what is known, urea uptake from the soil into plant roots is mediated by two types of transporters: the major intrinsic proteins (MIPs) and the DUR3 orthologs, mediating low- and high affinity urea transport, respectively. Here we characterized a MIP family member from Cucumis sativus, CsNIP2;1, with regard to its contribution to urea transport. We show that CsNIP2;1 is a plasma membrane transporter that mediates pH-dependent urea uptake when expressed in yeast. We also found that ectopic expression of CsNIP2;1 improves growth of wild-type Arabidopsis thaliana and rescues growth and development of the atdur3-3 mutant on medium with urea as the sole N source. In addition, CsNIP2;1 is transcriptionally up-regulated by N deficiency, urea and NO3 (-). These data and results from the analyses of the pattern of CsNIP2;1 expression in A. thaliana and cucumber suggest that CsNIP2;1 might be involved in multiple steps of urea-based N nutrition, including urea uptake and internal transport during N remobilization throughout seed germination and N delivery to developing tissues. PMID- 26858286 TI - AtC3H17, a Non-Tandem CCCH Zinc Finger Protein, Functions as a Nuclear Transcriptional Activator and Has Pleiotropic Effects on Vegetative Development, Flowering and Seed Development in Arabidopsis. AB - Despite increasing reports that CCCH zinc finger proteins function in plant development and stress responses, the functions and molecular aspects of many CCCH zinc finger proteins remain uncharacterized. Here, we characterized the biological and molecular functions of AtC3H17, a unique Arabidopsis gene encoding a non-tandem CCCH zinc finger protein. AtC3H17 was ubiquitously expressed throughout the life cycle of Arabidopsis plants and their organs. The rate and ratio of seed germination of atc3h17 mutants were slightly slower and lower, respectively, than those of the wild type (WT), whereas AtC3H17-overexpressing transgenic plants (OXs) showed an enhanced germination rate. atc3h17 mutant seedlings were smaller and lighter than WT seedlings while AtC3H17 OX seedlings were larger and heavier. In regulation of flowering time, atc3h17 mutants showed delayed flowering, whereas AtC3H17 OXs showed early flowering compared with the WT. In addition, overexpression of AtC3H17 affected seed development, displaying abnormalities compared with the WT. AtC3H17 protein was localized to the nucleus and showed transcriptional activation activity in yeast and Arabidopsis protoplasts. The N-terminal region of AtC3H17, containing a conserved EELR-like motif, was necessary for transcriptional activation activity, and the two conserved glutamate residues in the EELR-like motif played an important role in transcriptional activation activity. Real-time PCR and transactivation analyses showed that AtC3H17 might be involved in seed development via transcriptional activation of OLEO1, OLEO2 and CRU3. Our results suggest that AtC3H17 has pleiotropic effects on vegetative development such as seed germination and seedling growth, flowering and seed development, and functions as a nuclear transcriptional activator in Arabidopsis. PMID- 26858285 TI - Branch Pathway Blocking in Artemisia annua is a Useful Method for Obtaining High Yield Artemisinin. AB - There are many biosynthetic pathways competing for the metabolic flux with the artemisinin biosynthetic pathway in Artemisia annua L. To study the relationship between genes encoding enzymes at branching points and the artemisinin biosynthetic pathway, beta-caryophyllene, beta-farnesene and squalene were sprayed on young seedlings of A. annua. Transient expression assays indicated that the transcription levels of beta-caryophyllene synthase (CPS), beta farnesene synthase (BFS) and squalene synthase (SQS) were inhibited by beta caryophyllene, beta-farnesene and squalene, respectively, while expression of some artemisinin biosynthetic pathway genes increased. Thus, inhibition of these genes encoding enzymes at branching points may be helpful to improve the artemisinin content. For further study, the expression levels of four branch pathway genes CPS, BFS, germacrene A synthase (GAS) and SQS were down-regulated by the antisense method in A. annua. In anti-CPS transgenic plants, mRNA levels of BFS and ADS were increased, and the contents of beta-farnesene, artemisinin and dihydroartemisinic acid (DHAA) were increased by 212, 77 and 132%, respectively. The expression levels of CPS, SQS, GAS, amorpha-4,11-diene synthase (ADS), amorphadiene 12-hydroxylase (CYP71AV1) and aldehyde dehydrogenase 1 (ALDH1) were increased in anti-BFS transgenic plants and, at the same time, the contents of artemisinin and DHAA were increased by 77% and 54%, respectively, and the content of squalene was increased by 235%. In anti-GAS transgenic plants, mRNA levels of CPS, BFS, ADS and ALDH1 were increased. The contents of artemisinin and DHAA were enhanced by 103% and 130%, respectively. In anti-SQS transgenic plants, the transcription levels of BFS, GAS, CPS, ADS, CYP71AV1 and ALDH1 were all increased. Contents of artemisinin and DHAA were enhanced by 71% and 223%, respectively, while beta-farnesene was raised to 123%. The mRNA level of artemisinic aldehyde Delta11(13) reductase (DBR2) had changed little in almost all transgenic plants. PMID- 26858287 TI - Effects of Bleaching by Nitrogen Deficiency on the Quantum Yield of Photosystem II in Synechocystis sp. PCC 6803 Revealed by Chl Fluorescence Measurements. AB - Estimation of photosynthesis by Chl fluorescence measurement of cyanobacteria is always problematic due to the interference from respiratory electron transfer and from phycocyanin fluorescence. The interference from respiratory electron transfer could be avoided by the use of DCMU or background illumination by blue light, which oxidizes the plastoquinone pool that tends to be reduced by respiration. On the other hand, the precise estimation of photosynthesis in cells with a different phycobilisome content by Chl fluorescence measurement is difficult. By subtracting the basal fluorescence due to the phycobilisome and PSI, it becomes possible to estimate the precise maximum quantum yield of PSII in cyanobacteria. Estimated basal fluorescence accounted for 60% of the minimum fluorescence, resulting in a large difference between the 'apparent' yield and 'true' yield under high phycocyanin conditions. The calculated value of the 'true' maximum quantum yield of PSII was around 0.8, which was similar to the value observed in land plants. The results suggest that the cause of the apparent low yield reported in cyanobacteria is mainly ascribed to the interference from phycocyanin fluorescence. We also found that the 'true' maximum quantum yield of PSII decreased under nitrogen-deficient conditions, suggesting the impairment of the PSII reaction center, while the 'apparent' maximum quantum yield showed a marginal change under the same conditions. Due to the high contribution of phycocyanin fluorescence in cyanobacteria, it is essential to eliminate the influence of the change in phycocyanin content on Chl fluorescence measurement and to evaluate the 'true' photosynthetic condition. PMID- 26858288 TI - Exploiting the Substrate Promiscuity of Hydroxycinnamoyl-CoA:Shikimate Hydroxycinnamoyl Transferase to Reduce Lignin. AB - Lignin poses a major challenge in the processing of plant biomass for agro industrial applications. For bioengineering purposes, there is a pressing interest in identifying and characterizing the enzymes responsible for the biosynthesis of lignin. Hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyl transferase (HCT; EC 2.3.1.133) is a key metabolic entry point for the synthesis of the most important lignin monomers: coniferyl and sinapyl alcohols. In this study, we investigated the substrate promiscuity of HCT from a bryophyte (Physcomitrella) and from five representatives of vascular plants (Arabidopsis, poplar, switchgrass, pine and Selaginella) using a yeast expression system. We demonstrate for these HCTs a conserved capacity to acylate with p-coumaroyl-CoA several phenolic compounds in addition to the canonical acceptor shikimate normally used during lignin biosynthesis. Using either recombinant HCT from switchgrass (PvHCT2a) or an Arabidopsis stem protein extract, we show evidence of the inhibitory effect of these phenolics on the synthesis of p-coumaroyl shikimate in vitro, which presumably occurs via a mechanism of competitive inhibition. A structural study of PvHCT2a confirmed the binding of a non canonical acceptor in a similar manner to shikimate in the active site of the enzyme. Finally, we exploited in Arabidopsis the substrate flexibility of HCT to reduce lignin content and improve biomass saccharification by engineering transgenic lines that overproduce one of the HCT non-canonical acceptors. Our results demonstrate conservation of HCT substrate promiscuity and provide support for a new strategy for lignin reduction in the effort to improve the quality of plant biomass for forage and cellulosic biofuels. PMID- 26858289 TI - Transcriptional Framework of Male Gametogenesis in the Liverwort Marchantia polymorpha L. AB - In land plants, there are two types of male gametes: one is a non-motile sperm cell which is delivered to the egg cell by a pollen tube, and the other is a motile sperm cell with flagella. The molecular mechanism underlying the sexual reproduction with the egg and pollen-delivered sperm cell is well understood from studies using model plants such as Arabidopsis and rice. On the other hand, the sexual reproduction with motile sperm has remained poorly characterized, due to the lack of suitable models. Marchantia polymorpha L. is a model basal land plant with sexual reproduction involving an egg cell and bi-flagellated motile sperm. To understand the differentiation process of plant motile sperm, we analyzed the gene expression profile of developing antheridia of M. polymorpha. We performed RNA-sequencing experiments and compared transcript profiles of the male sexual organ (antheridiophore and antheridium contained therein), female sexual organ (archegoniophore) and a vegetative organ (thallus). Transcriptome analysis showed that the antheridium expresses nearly half of the protein-coding genes predicted in the genome, but it also has unique features. The antheridium transcriptome shares some common features with male gamete transcriptomes of angiosperms and animals, and homologs of genes involved in male gamete formation and function in angiosperms and animals were identified. In addition, we showed that some of them had distinct expression patterns in the spermatogenous tissue of developing antheridia. This study provides a transcriptional framework on which to study the molecular mechanism of plant motile sperm development in M. polymorpha as a model. PMID- 26858290 TI - Introduction to the Analysis of Survival Data in the Presence of Competing Risks. AB - Competing risks occur frequently in the analysis of survival data. A competing risk is an event whose occurrence precludes the occurrence of the primary event of interest. In a study examining time to death attributable to cardiovascular causes, death attributable to noncardiovascular causes is a competing risk. When estimating the crude incidence of outcomes, analysts should use the cumulative incidence function, rather than the complement of the Kaplan-Meier survival function. The use of the Kaplan-Meier survival function results in estimates of incidence that are biased upward, regardless of whether the competing events are independent of one another. When fitting regression models in the presence of competing risks, researchers can choose from 2 different families of models: modeling the effect of covariates on the cause-specific hazard of the outcome or modeling the effect of covariates on the cumulative incidence function. The former allows one to estimate the effect of the covariates on the rate of occurrence of the outcome in those subjects who are currently event free. The latter allows one to estimate the effect of covariates on the absolute risk of the outcome over time. The former family of models may be better suited for addressing etiologic questions, whereas the latter model may be better suited for estimating a patient's clinical prognosis. We illustrate the application of these methods by examining cause-specific mortality in patients hospitalized with heart failure. Statistical software code in both R and SAS is provided. PMID- 26858291 TI - ECG Response: February 9, 2016. PMID- 26858292 TI - Synchronous Multiple Ossifying Tumors of the Digits: Metastatic Cardiac Myxoma. PMID- 26858293 TI - Mitral Valve Prolapse Revisited. PMID- 26858294 TI - Inferior Vena Cava Filters, May-Thurner Syndrome, and Vein Stents. PMID- 26858295 TI - Letter by Sardu et al Regarding Article, "Circulating MicroRNA-30d Is Associated With Response to Cardiac Resynchronization Therapy in Heart Failure and Regulates Cardiomyocyte Apoptosis: A Translational Pilot Study". PMID- 26858297 TI - Letter by Poullis Regarding Article, "Efficacy of Long-Term beta-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery". PMID- 26858296 TI - Response to Letter Regarding Article, "Circulating MicroRNA-30d Is Associated With Response to Cardiac Resynchronization Therapy in Heart Failure and Regulates Cardiomyocyte Apoptosis: A Translational Pilot Study". PMID- 26858298 TI - Letter by Bergerot et al Regarding Article, "Efficacy of Long-Term beta-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery". PMID- 26858299 TI - Letter by Kardesoglu et al Regarding Article, "Efficacy of Long-Term beta-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery". PMID- 26858300 TI - Response to Letters Regarding Article, "Efficacy of Long-Term beta-Blocker Therapy for Secondary Prevention of Long-Term Outcomes After Coronary Artery Bypass Grafting Surgery". PMID- 26858301 TI - Correction. PMID- 26858302 TI - Phosphorylation of Ago2 and Subsequent Inactivation of let-7a RNP-Specific MicroRNAs Control Differentiation of Mammalian Sympathetic Neurons. AB - MicroRNAs (miRNAs) are small regulatory RNAs that regulate gene expression posttranscriptionally by base pairing to the target mRNAs in animal cells. KRas, an oncogene known to be repressed by let-7a miRNAs, is expressed and needed for the differentiation of mammalian sympathetic neurons and PC12 cells. We documented a loss of let-7a activity during this differentiation process without any significant change in the cellular level of let-7a miRNA. However, the level of Ago2, an essential component that is associated with miRNAs to form RNP specific miRNA (miRNP) complexes, shows an increase with neuronal differentiation. In this study, differentiation-induced phosphorylation and the subsequent loss of miRNA from Ago2 were noted, and these accounted for the loss of miRNA activity in differentiating neurons. Neuronal differentiation induces the phosphorylation of mitogen-activated protein kinase p38 and the downstream kinase mitogen- and stress-activated protein kinase 1 (MSK1). This in turn upregulates the phosphorylation of Ago2 and ensures the dissociation of miRNA from Ago2 in neuronal cells. MSK1-mediated miRNP inactivation is a prerequisite for the differentiation of neuronal cells, where let-7a miRNA gets unloaded from Ago2 to ensure the upregulation of KRas, a target of let-7a. We noted that the inactivation of let-7a is both necessary and sufficient for the differentiation of sympathetic neurons. PMID- 26858305 TI - Removal of locking implants with stripped screw heads. PMID- 26858303 TI - Cytokine-Like Factor 1, an Essential Facilitator of Cardiotrophin-Like Cytokine:Ciliary Neurotrophic Factor Receptor alpha Signaling and sorLA-Mediated Turnover. AB - Cardiotrophin-like cytokine:cytokine-like factor-1 (CLC:CLF-1) is a heterodimeric neurotropic cytokine that plays a crucial role during neuronal development. Mice lacking CLC:CLF-1 die soon after birth due to a suckling defect and show reduced numbers of motor neurons. Humans carrying mutations in CLC:CLF-1 develop similar disorders, known as Sohar-Crisponi or cold-induced sweating syndrome, and have a high risk of early death. It is well known that CLC binds the ciliary neurotrophic factor receptor alpha (CNTFRalpha) and is a prerequisite for signaling through the gp130/leukemia inhibitory factor receptor beta (LIFRbeta) heterodimer, whereas CLF-1 serves to promote the cellular release of CLC. However, the precise role of CLF-1 is unclear. Here, we report that CLF-1, based on its binding site for CLC and on two additional and independent sites for CNTFRalpha and sorLA, is a key player in CLC and CNTFRalpha signaling and turnover. The site for CNTFRalpha enables CLF-1 to promote CLC:CNTFRalpha complex formation and signaling. The second site establishes a link between the endocytic receptor sorLA and the tripartite CLC:CLF-1:CNTFRalpha complex and allows sorLA to downregulate the CNTFRalpha pool in stimulated cells. Finally, sorLA may bind and concentrate the tripartite soluble CLC:CLF-1:CNTFRalpha complex on cell membranes and thus facilitate its signaling through gp130/LIFRbeta. PMID- 26858306 TI - Is intramedullary nailing better than the use of volar locking plates for fractures of the distal radius? A meta-analysis of randomized controlled trials. AB - We conducted a meta-analysis of randomized controlled trials that compared the use of intramedullary nails and volar locking plates in distal radial fractures. PubMed, EMBASE and the Cochrane Collaboration Central database were used to find randomized controlled trials that met the eligibility criteria. Two reviewers screened the studies, extracted the data, evaluated the methodological quality and analysed the data with RevMan 5.1 software. No statistically significant differences were detected in the disability of the arm, shoulder and hand and the Gartland and Werley scores, radiographic parameters, wrist range of motion, grip strength, total complication rate and incidence of tendon rupture between the two groups. However, carpal tunnel syndrome occurred less often after intramedullary nailing. The two fixation methods achieved equal clinical, functional and radiological outcomes for primary fixation of the indicated types of distal radial fractures. LEVEL OF EVIDENCE: Therapeutic/LevelI. PMID- 26858307 TI - Sidestepping a trap: a commentary on 'why parents should not be told the sex of their fetus'. PMID- 26858304 TI - Balancing of B6 Vitamers Is Essential for Plant Development and Metabolism in Arabidopsis. AB - Vitamin B6 comprises a family of compounds that is essential for all organisms, most notable among which is the cofactor pyridoxal 5'-phosphate (PLP). Other forms of vitamin B6 include pyridoxamine 5'-phosphate (PMP), pyridoxine 5' phosphate (PNP), and the corresponding nonphosphorylated derivatives. While plants can biosynthesize PLP de novo, they also have salvage pathways that serve to interconvert the different vitamers. The selective contribution of these various pathways to cellular vitamin B6 homeostasis in plants is not fully understood. Although biosynthesis de novo has been extensively characterized, the salvage pathways have received comparatively little attention in plants. Here, we show that the PMP/PNP oxidase PDX3 is essential for balancing B6 vitamer levels in Arabidopsis thaliana. In the absence of PDX3, growth and development are impaired and the metabolite profile is altered. Surprisingly, RNA sequencing reveals strong induction of stress-related genes in pdx3, particularly those associated with biotic stress that coincides with an increase in salicylic acid levels. Intriguingly, exogenous ammonium rescues the growth and developmental phenotype in line with a severe reduction in nitrate reductase activity that may be due to the overaccumulation of PMP in pdx3. Our analyses demonstrate an important link between vitamin B6 homeostasis and nitrogen metabolism. PMID- 26858308 TI - Public funding of uterine transplantation. PMID- 26858309 TI - A Multi-Institution Phase I Trial of Ruxolitinib in Patients with Chronic Myelomonocytic Leukemia (CMML). AB - PURPOSE: To conduct a phase I clinical trial exploring the safety and efficacy of ruxolitinib, a JAK1/2 inhibitor, for chronic myelomonocytic leukemia (CMML). EXPERIMENTAL DESIGN: Patients with CMML-1 were included without regard to previous therapy. Key exclusion criteria included an absolute neutrophil count (ANC) <0.25 * 10(3) cells/dL and a platelet count <35 * 10(3) cells/dL. Four cohorts were enrolled using a "rolling six" study design, with doses ranging from 5 to 20 mg twice daily of ruxolitinib in 5-mg dose escalations. RESULTS: Between March 2013 and January 2015, 20 patients were enrolled and treated with ruxolitinib. Seventy percent of patients had the proliferative subtype and 47% had higher risk disease by the Global MD Anderson Scoring System. Eight patients (42%) received a prior hypomethylating agent. No dose-limiting toxicities for ruxolitinib were identified. One subject had grade (G)3 thrombocytopenia with no other drug-associated G3 or G4 adverse events. The mean duration of therapy was 122 days (range, 28-409 days). Four had hematologic improvement and one patient had a partial response per 2006 International Working Group (IWG) criteria. Five of 9 patients with splenomegaly had a reduction in spleen size. Ten of 11 patients with reported disease-related symptoms had clinically meaningful or complete resolution. When combining IWG and spleen responses, a total response rate of 35% (n = 7) was identified. Correlative analysis demonstrated a reduction in inflammatory cytokines and GM-CSF-dependent STAT5 phosphorylation. CONCLUSIONS: The recommended phase II dose of ruxolitinib is 20 mg twice daily. We demonstrate that ruxolitinib has promising activity in CMML with particular benefit in those with disease-related B symptoms that warrants further study. Clin Cancer Res; 22(15); 3746-54. (c)2016 AACRSee related commentary by Solary, p. 3707. PMID- 26858310 TI - HDAC Inhibition Induces MicroRNA-182, which Targets RAD51 and Impairs HR Repair to Sensitize Cells to Sapacitabine in Acute Myelogenous Leukemia. AB - PURPOSE: The double-strand breaks elicited by sapacitabine, a clinically active nucleoside analogue prodrug, are repaired by RAD51 and the homologous recombination repair (HR) pathway, which could potentially limit its toxicity. We investigated the mechanism by which histone deacetylase (HDAC) inhibitors targeted RAD51 and HR to sensitize acute myelogenous leukemia (AML) cells to sapacitabine. EXPERIMENTAL DESIGN: Chromatin immunoprecipitation identified the role of HDACs in silencing miR-182 in AML. Immunoblotting, gene expression, overexpression, or inhibition of miR-182 and luciferase assays established that miR-182 directly targeted RAD51. HR reporter assays, apoptotic assays, and colony forming assays established that the miR-182, as well as the HDAC inhibition mediated decreases in RAD51 inhibited HR repair and sensitized cells to sapacitabine. RESULTS: The gene repressors, HDAC1 and HDAC2, became recruited to the promoter of miR-182 to silence its expression in AML. HDAC inhibition induced miR-182 in AML cell lines and primary AML blasts. miR-182 targeted RAD51 protein both in luciferase assays and in AML cells. Overexpression of miR-182, as well as HDAC inhibition-mediated induction of miR-182 were linked to time- and dose dependent decreases in the levels of RAD51, an inhibition of HR, increased levels of residual damage, and decreased survival after exposure to double-strand damage inducing agents. CONCLUSIONS: Our findings define the mechanism by which HDAC inhibition induces miR-182 to target RAD51 and highlights a novel pharmacologic strategy that compromises the ability of AML cells to conduct HR, thereby sensitizing AML cells to DNA-damaging agents that activate HR as a repair and potential resistance mechanism. Clin Cancer Res; 22(14); 3537-49. (c)2016 AACR. PMID- 26858312 TI - Phase Ib Study of Enzalutamide in Combination with Docetaxel in Men with Metastatic Castration-Resistant Prostate Cancer. AB - PURPOSE: Preclinical evidence suggests that both docetaxel and enzalutamide target androgen receptor translocation and signaling. This phase Ib study assessed the safety, tolerability, and pharmacokinetics of docetaxel when administered with enzalutamide as first-line systemic chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC). EXPERIMENTAL METHODS: Docetaxel-naive patients received 21-day cycles of docetaxel (75 mg/m(2)). Enzalutamide (160 mg/day) was administered daily starting on day 2 of cycle 1. Patients were allowed to stop and restart docetaxel at any time following cycle 2. Treatment continued indefinitely until unacceptable toxicity or discontinuation due to investigator or patient preference. RESULTS: A total of 22 patients received docetaxel, of whom 21 also received enzalutamide. Docetaxel was administered for a median of 5.0 cycles and enzalutamide for a median of 12.0 months. With concomitant treatment, geometric mean docetaxel exposure decreased by 11.8%, whereas peak concentrations decreased by 3.7% relative to docetaxel alone. The most common toxicities observed during the period of concomitant therapy were neutropenia (86.4%) and fatigue (77.3%). Common toxicities observed with post-docetaxel enzalutamide were constipation (23.8%), decreased appetite (19.0%), fatigue (19.0%), and musculoskeletal pain (19.0%). Treatment with enzalutamide and docetaxel resulted in prostate-specific antigen decreases in almost all patients based on exploratory analysis of available baseline and on study prostate-specific antigen data. CONCLUSIONS: The combination of docetaxel and enzalutamide is feasible, although higher rates of neutropenia and neutropenic fever than anticipated were observed. Reductions in docetaxel exposure with enzalutamide coadministration were not considered clinically meaningful. This combination warrants further study in a larger mCRPC population. Clin Cancer Res; 22(15); 3774-81. (c)2016 AACR. PMID- 26858313 TI - Patient Understanding of HIV and Hepatitis C Testing in an Emergency Department with an Integrated Program. AB - INTRODUCTION: We implemented triage nurse rapid HIV and hepatitis C virus (HCV) screening, in parallel with physician diagnostic testing, in our urban emergency department (ED). METHODS: A 2-month cross-sectional survey was performed to determine the proportion of patients who correctly reported being tested for HIV and HCV. RESULTS: A total of 492 patients were surveyed. Fifty-one (70%) of the 73 patients who reported being HIV tested and 372 (89%) of the 419 patients who reported not being HIV tested were correct. Thirty (60%) of the 50 patients who reported being HCV tested and 416 (94%) of the 442 patients who reported not being HCV tested were correct. CONCLUSION: Although most ED patients correctly reported whether testing was performed, there were many who did not. Although ED screening programs for HIV and HCV serve as an important venue for screening, strategies to improve communication require attention. PMID- 26858314 TI - Lipid Changes in Virologically Suppressed HIV-Infected Patients Switching from any Antiretroviral Therapy to the Emtricitabine/Rilpivirine/Tenofovir Single Tablet: GeSida Study 8114. AB - We carried out a retrospective, multicenter study of a cohort of 298 asymptomatic HIV-infected patients who switched from a regimen based on 2 nucleoside reverse transcriptase inhibitors + protease inhibitor (PI)/nonnucleoside reverse transcriptase inhibitor or ritonavir-boosted PI monotherapy to emtricitabine/rilpivirine/tenofovir disoproxil fumarate (FTC/RPV/TDF) to analyze lipid changes. At 24 weeks, 284 (95.3%) patients were still taking the same regimen, maintaining similar CD4 counts as at baseline (651 versus 672 cells/mm(3), P = .08), and 98.9% of them with an undetectable viral load. Eight of the other 14 patients were lost to follow up and 6 (2.0%) ceased the new regimen: 3 due to adverse effects, 2 due to virologic failure, and 1 due to abandonment. The mean levels of fasting total cholesterol (TC), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides fell at 12 and 24 weeks, with no changes detected in the TC to HDL C ratio. PMID- 26858315 TI - The Rise and Fall of Efavirenz. PMID- 26858311 TI - Immunologic and Metabolic Features of Pancreatic Ductal Adenocarcinoma Define Prognostic Subtypes of Disease. AB - PURPOSE: Pancreatic ductal adenocarcinoma (PDA) is associated with an immunosuppressive microenvironment that supports the growth of the malignancy as well as immune system evasion. Here we examine markers of immunosuppression in PDA within the context of the glycolytic tumor microenvironment, their interrelationship with tumor biology and association with overall survival. EXPERIMENTAL DESIGN: We utilized tissue microarrays consisting of 223 PDA patients annotated for clinical stage, tumor size, lymph node involvement, and survival. Expression of CD163, FoxP3, PD-L1, and MCT4 was assessed by IHC and statistical associations were evaluated by univariate and multivariate analysis. Multimarker subtypes were defined by random forest analysis. Mechanistic interactions were evaluated using PDA cell lines and models for myeloid differentiation. RESULTS: PDA exhibits discrete expression of CD163, FoxP3, and PD-L1 with modest individual significance. However, combined low expression of these markers was associated with improved prognosis (P = 0.02). PDA tumor cells altered macrophage phenotype and function, which supported enhanced invasiveness in cell-based models. Lactate efflux mediated by MCT4 was associated with, and required for, the selective conversion of myeloid cells. Correspondingly, MCT4 expression correlated with immune markers in PDA cases, and increased the significance of prognostic subtypes (P = 0.002). CONCLUSIONS: There exists a complex interplay between PDA tumor cells and the host immune system wherein immunosuppression is associated with negative outcome. MCT4 expression, representative of the glycolytic state of PDA, contributes to the phenotypic conversion of myeloid cells. Thus, metabolic status of PDA tumors is an important determinant of the immunosuppressive environment. Clin Cancer Res; 22(14); 3606 17. (c)2016 AACR. PMID- 26858321 TI - Physical Functioning among Women 80 Years of Age and Older With and Without a Cancer History. AB - BACKGROUND: Females 80 years and older comprise 22% of the total U.S. survivor population, yet the impact of cancer on the physical well-being of women is this age group has not been well characterized. METHODS: We compared women, 80 years of age and older in the Women's Health Initiative extension 2, who did (n = 2,270) and did not (n = 20,272) have an adjudicated history of cancer during Women's Health Initiative enrollment; analyses focused on women >2-years postcancer diagnosis. The physical functioning subscale of the RAND-36 was the primary outcome. Demographic, health-status, and psychosocial covariates were drawn from Women's Health Initiative assessments. Analysis of covariance was used to examine the effect of cancer history on physical function, with and without adjustment for covariates. RESULTS: In adjusted models, women with a history of cancer reported significantly lower mean physical functioning (56.6, standard error [SE] 0.4) than those without a cancer history (58.0, SE 0.1), p = .002. In these models, younger current age, lower body mass index, increased physical activity, higher self-rated health, increased reported happiness, and the absence of noncancer comorbid conditions were all associated with higher physical functioning in both women with and without a history of cancer. CONCLUSIONS: Women older than 80 years of age with a cancer history have only a moderately lower level of physical function than comparably aged women without a cancer history. Factors associated with higher levels of physical functioning were similar in both groups. PMID- 26858322 TI - Aging Well: Observations From the Women's Health Initiative Study. AB - BACKGROUND: As the proportion of the population aged 80 and over accelerates, so does the value of understanding the processes of aging well. The purposes of this article are to: (a) review contemporary theoretical and conceptual perspectives on aging well, (b) describe indicators of aging well that reflect key concepts and perspectives as assessed in the Women's Health Initiative (WHI) and (c) characterize the status of aging among women aged 80 and older using data obtained from WHI participants at the WHI Extension 2 follow-up. METHODS: Data from the Lifestyle Questionnaire, which was administered from 2011 to 2012 during the WHI Follow-up Study (Extension 2), were analyzed to provide a profile of the WHI cohort with respect to aging well. RESULTS: Data revealed substantial diversity in the cohort with respect to the various measures of aging well. Although many reported physical functioning levels consistent with disability, most rated their health as good or better. Most reported moderately high levels of resilience, self-control, and self-mastery but lower levels of environmental mastery. Finally, the cohort reported high levels of optimal aging as reflected by their high levels of emotional well-being and moderately high levels of life satisfaction and social support, but more modest levels of personal growth and purpose in life. CONCLUSIONS: The wide range of some dimensions of aging well suggest that further examination of predictors of positive coping and resilience in the face of aging-related disability could identify opportunities to support and facilitate aging well among U.S. women. PMID- 26858323 TI - Physical Functioning Among Women Aged 80 Years and Older With Previous Fracture. AB - BACKGROUND: The oldest old are the fastest growing segment of the elderly population. Little is known regarding the associations of fracture history with physical functioning assessed after age 80. METHODS: Among 33,386 women surviving to age 80 years (mean +/- SD years 84.6 +/- 3.4), we examined the relationship between history of incident fracture after entry into the Women's Health Initiative (follow-up 15.2 +/- 1.3 years) and their physical functioning assessed using the RAND-36 instrument most proximal to 2012 end of follow-up. RESULTS: Baseline mean (+/-SD) physical function score was 82 (+/- 18). After adjustment for demographic and medical characteristics, fracture at each site, including hip, upper limb, lower limb, and central body, was associated with significantly lower subsequent physical functioning (all p < .001). Hip, upper leg, spine, and pelvis fractures were particularly related with lower physical functioning scores, 11.7 (95% CI: 10.3, 13.1), 10.5 (8.8, 12.3), 9.8 (8.9, 10.8), and 8.7 (7.2, 10.2) units lower, respectively, compared with women without fracture (each p < .0001). Compared with women without central site fracture, women with central site fractures also had lower physical functioning scores (10.0 [9.3, 10.8] units lower]; p < .0001). In case-only analysis of fractures, older age, less than 1 year since fracture, one or more additional sites fractured, history of cardiovascular disease or cancer, higher body mass index, and no alcohol intake in the past 3 months also were independent predictors of lower physical functioning score (all p < .05). CONCLUSIONS: Among women surviving to 80 years and older, prior fracture is associated with lower current physical functioning, regardless of anatomical site of fracture, independent of other major predictors of disability. PMID- 26858324 TI - The Relationship of Cardiovascular Disease to Physical Functioning in Women Surviving to Age 80 and Above in the Women's Health Initiative. AB - BACKGROUND: Cardiovascular disease (CVD) is highly prevalent at ages 80 and above. The association of physical functioning (PF), a key to an optimal aging trajectory, with CVD and specific CVD diagnosis in women who survive to age 80 and above has not been described previously and has important public health significance given our aging population. METHODS: Women's Health Initiative participants aged 80 years or older at the time of self-reporting PF (RAND SF-36) were studied in relationship to CVD diagnosis, whether present at study baseline (1993-1998) or diagnosed during follow-up through 2012. Cross-sectional analyses utilized demographic, medical, lifestyle, and psycho-social questionnaire data from baseline or updated at the time of self-reported PF. RESULTS: Among 27,145 older Women's Health Initiative participants, 22.0% (N = 5,959) had been diagnosed with CVD, specifically: 11.3% (N = 3,071) with coronary heart disease; 4.7% (N = 1,279), stroke; 5.2% (N = 1,397), venous thromboembolism; 2.7% (N = 737), peripheral arterial disease; and 2.7% (N = 725), congestive heart failure. PF scores (mean +/- SE) were significantly (p < .0001) higher without CVD (60.0 +/- 26.9), compared with any CVD (47.9 +/- 27.3), and for each specific CVD diagnosis: coronary heart disease (48.8 +/- 27.1); stroke (44.8 +/- 27.9); venous thromboembolism (48.9 +/- 27.4); peripheral arterial disease (41.9 +/- 2.2); and congestive heart failure (38.8 +/- 26.1). Regardless of CVD diagnosis, higher PF was associated with: younger age at the time of PF assessment; lower body mass index; higher recreational physical activity; better self-reported general health; fewer hip fractures after age 55; no history of arthritis; and no recent use of non-steroidal anti-inflammatory drugs. CONCLUSIONS: Older women with any CVD, and particularly women with congestive heart failure or peripheral arterial disease, reported significantly lower PF compared to women with no CVD. Regardless of CVD diagnosis, higher PF was strongly associated with a more active lifestyle and lower body mass index, suggesting potential intervention targets for more optimal aging. PMID- 26858325 TI - The Impact of Multimorbidity and Coronary Disease Comorbidity on Physical Function in Women Aged 80 Years and Older: The Women's Health Initiative. AB - BACKGROUND: A better understanding of medically centered outcomes, such as physical function, for older women with multiple chronic conditions is a national public health priority. METHODS: The prevalence of multimorbidity (defined as having 2 chronic conditions from a list of 12) and comorbidity with coronary disease (CHD) were calculated for 33,386 women who were enrolled in the Women's Health Initiative since 1993-1998 and were >= 80 years old by mid-September 2012. Associations between multimorbidity and CHD comorbidity on RAND-36 physical function scores were estimated using linear regression models. RESULTS: The prevalence of multimorbidity in this sample was 59%. Women with 0-1 chronic condition had a mean physical function score of 74 (95% confidence interval [CI]: 73, 74). Relative decrements in physical function scores were -8 (95% CI: -8, 7), -13 (95% CI: -14, -12) and -19 (95% CI: -20, -18) in women with 2, 3, and >= 4 chronic conditions, respectively. Women with CHD in combination with hip fractures or cognitive impairment had the largest adjusted decreases in physical function scores compared to the scores for women with CHD only. The impact of select characteristics on physical function scores between multimorbid and non multimorbid women were similar; however, overall mean physical functions scores were lower for women with multmorbidity. CONCLUSIONS: Multimorbidity profoundly impacted physical functioning in women aged more than 80 years. Modifiable risk factors, such as obesity and physical activity, were similar in older women regardless of multimorbidity status and provide targets for health interventions aimed at preventing loss of late-age physical functioning. PMID- 26858326 TI - Predictors of Optimal Cognitive Aging in 80+ Women: The Women's Health Initiative Memory Study. AB - BACKGROUND: Independent predictors of preserved cognitive functioning and factors associated with maintaining high preserved cognitive function in women >= 80 years remain elusive. METHODS: Two thousand two hundred twenty-eight women with a mean age of 85 years who participated in the Women's Health Initiative Memory Study were classified as cognitively normal (n = 1,905, 85.5%), mild cognitive impairment (n = 88, 3.9%), dementia (n = 121, 5.4%) or other cognitive impairment (n = 114, n = 5.1%) by central adjudication. Global cognitive functioning was assessed using telephone interview for cognitive status-modified in those women who did not meet cognitive impairment criteria. Differences between women grouped by cognitive status with respect to each potential risk factor were assessed using chi-squared tests and t-tests. Backward stepwise logistic regression was used to select factors that were independently associated with cognitive status. RESULTS: Factors associated with preserved cognitive functioning were younger age, higher education, and family incomes, being non-Hispanic white, better emotional wellbeing, fewer depressive symptoms, more insomnia complaints, being free of diabetes, and not carrying the apolipoprotein E-epsilon 4 allele. Cognitively normal women who demonstrated sustained high preserved cognition were younger, more educated, and endorsed better self-reported general health, emotional wellbeing, and higher physical functioning. CONCLUSIONS: Addressing sociodemographic disparities such as income inequality, and targeting interventions to improve depressive symptoms and vascular risk factors, including diabetes, may play an important role in preserving cognition among women who survive to 80 years of age. Person-centered approaches that combine interventions to improve physical, cognitive, and psychosocial functioning may promote maintenance of high preserved cognitive health in the oldest-old. PMID- 26858327 TI - Global Quality of Life Among WHI Women Aged 80 Years and Older. AB - BACKGROUND: The number of older adults living to age 80 and older is increasing rapidly, particularly among women. Correlates of quality of life (QOL) in very advanced ages are not known. We examined the association of demographic, social psychological, lifestyle, and physical health variables with global QOL in a Women's Health Initiative (WHI) cohort of women aged 80 and older. METHODS: 26,299 WHI participants, who had completed a recent psychosocial and medical update, were included in these analyses. Global QOL was assessed by a single item, asking the women to rate their overall QOL on a scale from 0 to 10. Characteristics of the women were examined by the level of their transformed global QOL scores (<=50, 50-70, >=70), and multiple regression was used to examine which demographic, social-psychological, lifestyle and health variables were independently associated with higher global QOL. RESULTS: Social psychological and current health variables were more strongly associated with global QOL than a history of selected comorbid conditions. In particular, higher self-rated health and fewer depressive symptoms were the most strongly associated with better global QOL in WHI women >=80 years. CONCLUSIONS: Interventions to reduce depressive symptoms and improve health may lead to better self-reported health and global QOL among older women. Physical and mental health screenings followed by evidence-based interventions are imperative in geriatric care. PMID- 26858328 TI - Functional Independence in Late-Life: Maintaining Physical Functioning in Older Adulthood Predicts Daily Life Function after Age 80. AB - BACKGROUND: We examined physical functioning (PF) trajectories (maintaining, slowly declining, and rapidly declining) spanning 15 years in older women aged 65 80 and protective factors that predicted better current levels and less decline in functional independence outcomes after age 80. METHODS: Women's Health Initiative extension participants who met criteria (enrolled in either the clinical trial or observational study cohort, >80 years at the data release cutoff, PF survey data from initial enrollment to age 80, and functional independence survey data after age 80) were included in these analyses (mean [SD] age = 84.0 [1.4] years; N = 10,478). PF was measured with the SF-36 (mean = 4.9 occasions). Functional independence was measured by self-reported level of dependence in basic and instrumental activities of daily living (ADLs and IADLs) (mean = 3.4 and 3.3 occasions). RESULTS: Maintaining consistent PF in older adulthood extends functional independence in ADL and IADL in late-life. Protective factors shared by ADL and IADL include maintaining PF over time, self reported excellent or very good health, no history of hip fracture after age 55, and no history of cardiovascular disease. Better IADL function is uniquely predicted by a body mass index less than 25 and no depression. Less ADL and IADL decline is predicted by better self-reported health, and less IADL decline is uniquely predicted by having no history of hip fracture after age 55. CONCLUSIONS: Maintaining or improving PF and preventing injury and disease in older adulthood (ages 65-80) has far-reaching implications for improving late life (after age 80) functional independence. PMID- 26858329 TI - Correlates of Successful Aging in Racial and Ethnic Minority Women Age 80 Years and Older: Findings from the Women's Health Initiative. AB - BACKGROUND: Most research has focused on definitions and predictors of successful aging. However, racial/ethnic minorities are often under represented in this research. Given that the U.S. population is aging and becoming more racially diverse, we examined correlates of "successful aging," as defined by physical functioning and overall quality of life (QOL), among racial/ethnic minority women aged 80 years and older in the Women's Health Initiative. METHODS: Participants included 1,924 racial/ethnic minority women (African Americans, Asian/Pacific Islanders, Hispanic/Latinos, and American Indian/Alaskan Natives) 80 years of age and older who are enrolled in the Women's Health Initiative and have physical functioning data after turning 80 years of age. Analysis of covariance was used to examine between and within group differences in physical functioning and selfrated overall QOL for African Americans, Asian/Pacific Islanders, and Hispanic/Latinos. RESULTS: We found no significant differences in physical functioning between racial/ethnic minority groups in adjusted analyses. However, overall QOL was significantly different between racial/ethnic minority groups. Age, recreational physical activity, and overall selfrated health were independent correlates of physical functioning across racial/ethnic minority groups, whereas overall selfrated health was the only consistent correlate of overall QOL across the minority groups for the within minority group comparisons. CONCLUSIONS: Between racial/ethnic minority group differences in physical functioning are largely explained by demographic, psychosocial, behavioral, and health-related variables. We found statistically significant differences in selfrated overall QOL between racial/ethnic minority groups. PMID- 26858330 TI - Sexual Polyploidization in Medicago sativa L.: Impact on the Phenotype, Gene Transcription, and Genome Methylation. AB - Polyploidization as the consequence of 2n gamete formation is a prominent mechanism in plant evolution. Studying its effects on the genome, and on genome expression, has both basic and applied interest. We crossed two diploid (2n = 2x = 16) Medicago sativa plants, a subsp. falcata seed parent, and a coerulea * falcata pollen parent that form a mixture of n and 2n eggs and pollen, respectively. Such a cross produced full-sib diploid and tetraploid (2n = 4x = 32) hybrids, the latter being the result of bilateral sexual polyploidization (BSP). These unique materials allowed us to investigate the effects of BSP, and to separate the effect of intraspecific hybridization from those of polyploidization by comparing 2x with 4x full sib progeny plants. Simple sequence repeat marker segregation demonstrated tetrasomic inheritance for all chromosomes but one, demonstrating that these neotetraploids are true autotetraploids. BSP brought about increased biomass, earlier flowering, higher seed set and weight, and larger leaves with larger cells. Microarray analyses with M. truncatula gene chips showed that several hundred genes, related to diverse metabolic functions, changed their expression level as a consequence of polyploidization. In addition, cytosine methylation increased in 2x, but not in 4x, hybrids. Our results indicate that sexual polyploidization induces significant transcriptional novelty, possibly mediated in part by DNA methylation, and phenotypic novelty that could underpin improved adaptation and reproductive success of tetraploid M. sativa with respect to its diploid progenitor. These polyploidy-induced changes may have promoted the adoption of tetraploid alfalfa in agriculture. PMID- 26858331 TI - Final Results of the Sunbelt Melanoma Trial: A Multi-Institutional Prospective Randomized Phase III Study Evaluating the Role of Adjuvant High-Dose Interferon Alfa-2b and Completion Lymph Node Dissection for Patients Staged by Sentinel Lymph Node Biopsy. AB - PURPOSE: The Sunbelt Melanoma Trial is a prospective randomized trial evaluating the role of high-dose interferon alfa-2b therapy (HDI) or completion lymph node dissection (CLND) for patients with melanoma staged by sentinel lymph node (SLN) biopsy. PATIENTS AND METHODS: Patients were eligible if they were age 18 to 70 years with primary cutaneous melanoma >= 1.0 mm Breslow thickness and underwent SLN biopsy. In Protocol A, patients with a single tumor-positive lymph node after SLN biopsy underwent CLND and were randomly assigned to observation versus HDI. In Protocol B, patients with tumor-negative SLN by standard histopathology and immunohistochemistry underwent molecular staging by reverse transcriptase polymerase chain reaction (RT-PCR). Patients positive by RT-PCR were randomly assigned to observation versus CLND versus CLND+HDI. Primary end points were disease-free survival (DFS) and overall survival (OS). RESULTS: In the Protocol A intention-to-treat analysis, there were no significant differences in DFS (hazard ratio, 0.82; P = .45) or OS (hazard ratio, 1.10; P = .68) for patients randomly assigned to HDI versus observation. In the Protocol B intention-to-treat analysis, there were no significant differences in overall DFS (P = .069) or OS (P = .77) across the three randomized treatment arms. Similarly, efficacy analysis (excluding patients who did not receive the assigned treatment) did not demonstrate significant differences in DFS or OS in Protocol A or Protocol B. Median follow-up time was 71 months. CONCLUSION: No survival benefit for adjuvant HDI in patients with a single positive SLN was found. Among patients with tumor negative SLN by conventional pathology but with melanoma detected in the SLN by RT-PCR, there was no OS benefit for CLND or CLND+HDI. PMID- 26858332 TI - Influence of the Acidic Beverage Cola on the Absorption of Erlotinib in Patients With Non-Small-Cell Lung Cancer. AB - PURPOSE: Erlotinib depends on stomach pH for its bioavailability. When erlotinib is taken concurrently with a proton pump inhibitor (PPI), stomach pH increases, which results in a clinically relevant decrease of erlotinib bioavailability. We hypothesized that this drug-drug interaction is reversed by taking erlotinib with the acidic beverage cola. The effects of cola on erlotinib bioavailability in patients not treated with a PPI were also studied. PATIENTS AND METHODS: In this randomized, cross-over, pharmacokinetic study in patients with non-small-cell lung cancer, we studied intrapatient differences in absorption (area under the plasma concentration time curve [AUC0-12h]) after a 7-day period of concomitant treatment with erlotinib, with or without esomeprazole, with either cola or water. At the 7th and 14th day, patients were hospitalized for 1 day for pharmacokinetic sampling. RESULTS: Twenty-eight evaluable patients were included in the analysis. In patients treated with erlotinib and esomeprazole with cola, the mean AUC0-12h increased 39% (range, -12% to 136%; P = .004), whereas in patients not treated with the PPI, the mean AUC0-12h was only slightly higher (9%; range, -10% to +30%; P = .03) after erlotinib intake with cola. CONCLUSION: Cola intake led to a clinically relevant and statistically significant increase in the bioavailability of erlotinib during esomeprazole treatment. In patients not treated with the PPI, the effects of cola were marginal. These findings can be used to optimize the management of drug-drug interactions between PPIs and erlotinib. PMID- 26858334 TI - Longitudinal Assessment of Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia Treated on a Contemporary Chemotherapy Protocol. AB - PURPOSE: Survivors of childhood acute lymphoblastic leukemia (ALL) treated with CNS-directed chemotherapy are at risk for neurocognitive deficits. Prospective longitudinal studies are needed to clarify the neurodevelopmental trajectory in this vulnerable population. METHODS: Patients enrolled in the St. Jude Total Therapy Study XV, which omitted prophylactic cranial radiation therapy in all patients, completed comprehensive neuropsychological assessments at induction (n = 142), end of maintenance (n = 243), and 2 years after completion of therapy (n = 211). We report on longitudinal change in neurocognitive function and predictors of neurocognitive outcomes 2 years after completing therapy. RESULTS: Neurocognitive function was largely age appropriate 2 years after completing therapy; however, the overall group demonstrated significant attention deficits and a significantly greater frequency of learning problems as compared with national normative data (all P <= .005). Higher-intensity CNS-directed chemotherapy conferred elevated risk for difficulties in attention, processing speed, and academics (all P <= .01). The rate and direction of change in performance and caregiver-reported attention difficulties differed significantly by age at diagnosis and sex. End-of-therapy attention problems predicted lower academic scores 2 years later, with small to moderate effect sizes (?r?= 0.17 to 0.25, all P <= .05). CONCLUSION: Two years after chemotherapy-only treatment, neurocognitive function is largely age appropriate. Nonetheless, survivors remain at elevated risk for attention problems that impact real-world functioning. Attention problems at the end of therapy predicted decreased academics 2 years later, suggesting an amplified functional impact of discrete neurocognitive difficulties. Age at diagnosis and patient sex may alter neurocognitive development in survivors of childhood ALL treated with chemotherapy-only protocols. PMID- 26858335 TI - A Randomized, Open-Label, Multicenter, Phase III Study of Epoetin Alfa Versus Best Standard of Care in Anemic Patients With Metastatic Breast Cancer Receiving Standard Chemotherapy. AB - PURPOSE: An open-label, noninferiority study to evaluate the impact of epoetin alfa (EPO) on tumor outcomes when used to treat anemia in patients receiving chemotherapy for metastatic breast cancer. METHODS: Women with hemoglobin <= 11.0 g/dL, receiving first- or second-line chemotherapy for metastatic breast cancer, were randomly assigned to EPO 40,000 IU subcutaneously once a week or best standard of care. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, time to tumor progression, overall response rate, RBC transfusions, and thrombotic vascular events. RESULTS: In 2,098 patients randomly assigned, median PFS (based on investigator-determined disease progression [PD]) was 7.4 months in both groups (hazard ratio [HR], 1.089; 95% CI, 0.988 to 1.200); upper bound exceeded prespecified noninferiority margin of 1.15. Median PFS per independent review committee-determined PD was 7.6 months in both groups (HR, 1.028; 95% CI, 0.922 to 1.146); upper bound did not exceed prespecified noninferiority margin. Median overall survival at clinical cutoff (1,337 deaths) was 17.2 months in the EPO and 17.4 months in the best standard of care group (HR, 1.057; 95% CI, 0.949 to 1.177), median time to tumor progression was 7.5 months in both groups (HR, 1.094; 95% CI, 0.991 to 1.209), and overall response rate was 50% versus 51% (odds ratio, 0.950; 95% CI, 0.799 to 1.130). RBC transfusions were 5.8% versus 11.4% (P < .001), and thrombotic vascular events were 2.8% versus 1.4% (P = .038), respectively. CONCLUSION: The primary end point, PFS based on investigator-determined PD, did not meet noninferiority criteria. As a consistency assessment with the primary finding, PFS based on independent review committee-determined PD met noninferiority criteria. Overall, this study did not achieve noninferiority objective in ruling out a 15% increased risk in PD/death. RBC transfusion should be the preferred approach for the management of anemia in this population. PMID- 26858336 TI - First-in-Human Phase I/II Study of NEOD001 in Patients With Light Chain Amyloidosis and Persistent Organ Dysfunction. AB - PURPOSE: Light chain (AL) amyloidosis is caused by the accumulation of misfolded proteins, which induces the dysfunction of vital organs. NEOD001 is a monoclonal antibody targeting these misfolded proteins. We report interim data from a phase I/II dose-escalation/expansion study of NEOD001 in patients with AL amyloidosis and persistent organ dysfunction (NCT01707264). PATIENTS AND METHODS: Patients who had completed at least one previous anti-plasma cell-directed therapy, had partial hematologic response or better, and had persistent organ dysfunction received NEOD001 intravenously every 28 days. Dose levels of 0.5, 1, 2, 4, 8, 16, and 24 mg/kg were evaluated (3 + 3 study design). Primary objectives were to determine the maximum tolerated dose and the recommended dose for future studies and to evaluate safety/tolerability. Secondary and exploratory objectives included pharmacokinetics, immunogenicity, and organ responses on the basis of published consensus criteria. RESULTS: Twenty-seven patients were enrolled in seven cohorts (dose-escalation component). No drug-related serious adverse events (AEs), discontinuations because of drug-related AEs, dose-limiting toxicities, or antidrug antibodies were reported. The most frequent AEs were fatigue, upper respiratory tract infection, cough, and dyspnea. Recommended dosing was 24 mg/kg. Pharmacokinetics support intravenous dosing every 28 days. Of 14 cardiac evaluable patients, eight (57%) met the criteria for cardiac response and six (43%) had stable disease. Of 15 renal-evaluable patients, nine (60%) met the criteria for renal response and six (40%) had stable disease. CONCLUSION: Monthly infusions of NEOD001 were safe and well tolerated. Recommended future dosing was 24 mg/kg. Organ response rates compared favorably with those reported previously for chemotherapy. A phase II expansion is ongoing. A global phase III study (NCT02312206) has been initiated. Antibody therapy targeting misfolded proteins is a potential new therapy for the management of AL amyloidosis. PMID- 26858337 TI - Determinants of Early Mortality Among 37,568 Patients With Colon Cancer Who Participated in 25 Clinical Trials From the Adjuvant Colon Cancer Endpoints Database. AB - PURPOSE: Factors associated with early mortality after surgery and treatment with adjuvant chemotherapy in colon cancer are poorly understood. We aimed to characterize the determinants of early mortality in a large cohort of colon cancer trial participants. METHODS: A pooled analysis of 37,568 patients in 25 randomized trials of adjuvant systemic therapy was conducted. Multivariable logistic regression models with several definitions of early mortality (30, 60, and 90 days, and 6 months) were constructed, adjusting for clinically and statistically significant variables. A nomogram for 6-month mortality was developed and validated. RESULTS: Median age among patients was 61 years, patient demographics included 54% men and 90% White, 29% and 71% had stage II and III disease, respectively, and 79%, 20%, and 1% had an Eastern Cooperative Oncology Group performance status (PS) of 0, 1, and >= 2, respectively. Early mortality was low: 0.3% at 30 days, 0.6% at 60 days, 0.8% at 90 days, and 1.4% at 6 months. Of those patients who died by 6 months post-random assignment, 40% had documented disease recurrence prior to death. Early disease recurrence was associated with a markedly increased risk of death during the first 6 months post-treatment (hazard ratio, 82.6; 95%CI, 66.9 to 102.1). In prognostic analyses, advanced age, male sex, poorer PS, increasing ratio of positive to examined lymph nodes, earlier decade of enrollment, and higher tumor stage and grade predicted a greater likelihood of early mortality, whereas treatment received was not strongly predictive. A multivariable model for 6-month mortality showed strong optimism adjusted discrimination (concordance index, 0.73) and calibration. CONCLUSION: Early mortality was infrequent but more prevalent in patients with advanced age and a PS of >= 2, underscoring the need to carefully consider the risk-to-benefit ratio when making treatment decisions in these subgroups. PMID- 26858338 TI - Reply to S. Alanee et al. PMID- 26858340 TI - Cardiovascular Disease Mortality After Diagnosis With Extragonadal Germ Cell Tumors. PMID- 26858341 TI - FUT1 genetic variants impact protein glycosylation of porcine intestinal mucosa. AB - A massive use of antibiotics in industrial pig production is a major cause of the rapidly rising bacterial resistance to antibiotics. An enhanced understanding of infectious diseases and of host-microbe interactions has the potential to explore alternative ways to improve pig health and reduce the need for antibiotics. Host microbe interactions depend on host-expressed glycans and microbe-carrying lectins. In this study, a G > A (nucleotide 307) missense mutation in the porcine alpha1,2fucosyltransferase 1 gene (FUT1), which has been reported to prevent infections by the common porcine enteric pathogen F18 fimbriated Escherichia coli, provided a unique opportunity to study glycan structures potentially involved in intestinal infections. N- and O-Linked glycans of the intestinal mucosa proteins were characterized in detail using LC-MS/MS. Relative abundances of all glycans were determined and compared between four heterozygous pigs (FUT1 307(A/G)) and four age-matched homozygous pigs from the same 2 litters carrying the missense FUT1 gene constellation (FUT1-307(A/A)). None of the characterized 48 N-linked glycans was found to be regulated by the FUT1 missense mutation, while 11 of the O-linked glycans showed significantly altered abundances between the two genotypes. The overall abundance of H-antigen carrying structures was decreased fivefold, while H-antigen precursors and sialylated structures were relatively more abundant in pigs with the FUT1 missense mutation. These results provide insight into the role of FUT1 on intestinal glycosylation, improve our understanding of how variation in FUT1 can modulate host-microbe interactions, and suggest that the FUT1 genetic variant may help to improve pig gut health. PMID- 26858342 TI - Residential segregation, dividing walls and mental health: a population-based record linkage study. AB - BACKGROUND: Neighbourhood segregation has been described as a fundamental determinant of physical health, but literature on its effect on mental health is less clear. While most previous research has relied on conceptualised measures of segregation, Northern Ireland is unique as it contains physical manifestations of segregation in the form of segregation barriers (or 'peacelines') which can be used to accurately identify residential segregation. METHODS: We used population wide health record data on over 1.3 million individuals, to analyse the effect of residential segregation, measured by both the formal Dissimilarity Index and by proximity to a segregation barrier, on the likelihood of poor mental health. RESULTS: Using multilevel logistic regression models, we found residential segregation measured by the Dissimilarity Index poses no additional risk to the likelihood of poor mental health after adjustment for area-level deprivation. However, residence in an area segregated by a 'peaceline' increases the likelihood of antidepressant medication by 19% (OR=1.19, 95% CI 1.14 to 1.23) and anxiolytic medication by 39% (OR=1.39, 95% CI 1.32 to 1.48), even after adjustment for gender, age, conurbation, deprivation and crime. CONCLUSIONS: Living in an area segregated by a 'peaceline' is detrimental to mental health suggesting segregated areas characterised by a heightened sense of 'other' pose a greater risk to mental health. The difference in results based on segregation measure highlights the importance of choice of measure when studying segregation. PMID- 26858339 TI - Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. AB - PURPOSE: To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. METHODS: A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. RECOMMENDATIONS: In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences. PMID- 26858343 TI - Reversal of murine alcoholic steatohepatitis by pepducin-based functional blockade of interleukin-8 receptors. AB - OBJECTIVE: Alcoholic steatohepatitis is a life-threatening condition with short term mortality up to 40%. It features hepatic neutrophil infiltration and blood neutrophilia, and may evolve from ethanol-induced breakdown of the enteric barrier and consequent bacteraemia. Signalling through CXCR1/2 G-protein-coupled receptors (GPCRs), the interleukin (IL)-8 receptors, is critical for the recruitment and activation of neutrophils. We have developed short lipopeptides (pepducins), which inhibit post-ligand GPCR activation precisely targeting individual GPCRs. DESIGN: Experimental alcoholic liver disease was induced by administering alcohol and a Lieber-DeCarli high-fat diet. CXCR1/2 GPCRs were blocked via pepducins either from onset of the experiment or after disease was fully established. Hepatic inflammatory infiltration, hepatocyte lipid accumulation and overall survival were assessed as primary outcome parameters. Neutrophil activation was assessed by myeloperoxidase activity and liver cell damage by aspartate aminotransferase and alanine aminotransferase plasma levels. Chemotaxis assays were performed to identify chemoattractant signals derived from alcohol-exposed hepatocytes. RESULTS: Here, we show that experimental alcoholic liver disease is driven by CXCR1/2-dependent activation of neutrophils. CXCR1/2 specific pepducins not only protected mice from liver inflammation, weight loss and mortality associated with experimental alcoholic liver disease, but therapeutic administration cured disease and prevented further mortality in fully established disease. Hepatic neutrophil infiltration and triglyceride accumulation was abrogated by CXCR1/2 blockade. Moreover, CXCL-1 plasma levels were decreased with the pepducin therapy as was the transcription of hepatic IL 1beta mRNA. CONCLUSIONS: We propose that high circulating IL-8 in human alcoholic hepatitis may cause pathogenic overzealous neutrophil activation, and therapeutic blockade via pepducins merits clinical study. PMID- 26858346 TI - Pregnancy and crash risk study wins Bruce Squires Award. PMID- 26858345 TI - CIHR spurns Aboriginal researchers' call for reconciliation. PMID- 26858344 TI - Integrin beta3 inhibition is a therapeutic strategy for supravalvular aortic stenosis. AB - The aorta is the largest artery in the body, yet processes underlying aortic pathology are poorly understood. The arterial media consists of circumferential layers of elastic lamellae and smooth muscle cells (SMCs), and many arterial diseases are characterized by defective lamellae and excess SMCs; however, a mechanism linking these pathological features is lacking. In this study, we use lineage and genetic analysis, pharmacological inhibition, explant cultures, and induced pluripotent stem cells (iPSCs) to investigate supravalvular aortic stenosis (SVAS) patients and/or elastin mutant mice that model SVAS. These experiments demonstrate that multiple preexisting SMCs give rise to excess aortic SMCs in elastin mutants, and these SMCs are hyperproliferative and dedifferentiated. In addition, SVAS iPSC-derived SMCs and the aortic media of elastin mutant mice and SVAS patients have enhanced integrin beta3 levels, activation, and downstream signaling, resulting in SMC misalignment and hyperproliferation. Reduced beta3 gene dosage in elastin-null mice mitigates pathological aortic muscularization, SMC misorientation, and lumen loss and extends survival, which is unprecedented. Finally, pharmacological beta3 inhibition in elastin mutant mice and explants attenuates aortic hypermuscularization and stenosis. Thus, integrin beta3-mediated signaling in SMCs links elastin deficiency and pathological stenosis, and inhibiting this pathway is an attractive therapeutic strategy for SVAS. PMID- 26858347 TI - Two cases of cardiac glycoside poisoning from accidental foxglove ingestion. PMID- 26858349 TI - Dear L. PMID- 26858350 TI - Blue man syndrome. PMID- 26858348 TI - Risk of suicide after a concussion. AB - BACKGROUND: Head injuries have been associated with subsequent suicide among military personnel, but outcomes after a concussion in the community are uncertain. We assessed the long-term risk of suicide after concussions occurring on weekends or weekdays in the community. METHODS: We performed a longitudinal cohort analysis of adults with diagnosis of a concussion in Ontario, Canada, from Apr. 1, 1992, to Mar. 31, 2012 (a 20-yr period), excluding severe cases that resulted in hospital admission. The primary outcome was the long-term risk of suicide after a weekend or weekday concussion. RESULTS: We identified 235,110 patients with a concussion. Their mean age was 41 years, 52% were men, and most (86%) lived in an urban location. A total of 667 subsequent suicides occurred over a median follow-up of 9.3 years, equivalent to 31 deaths per 100,000 patients annually or 3 times the population norm. Weekend concussions were associated with a one-third further increased risk of suicide compared with weekday concussions (relative risk 1.36, 95% confidence interval 1.14-1.64). The increased risk applied regardless of patients' demographic characteristics, was independent of past psychiatric conditions, became accentuated with time and exceeded the risk among military personnel. Half of these patients had visited a physician in the last week of life. INTERPRETATION: Adults with a diagnosis of concussion had an increased long-term risk of suicide, particularly after concussions on weekends. Greater attention to the long-term care of patients after a concussion in the community might save lives because deaths from suicide can be prevented. PMID- 26858351 TI - Genetic discrimination legislation in Canada: moving from rhetoric to real debate. PMID- 26858352 TI - Zika virus infection. PMID- 26858353 TI - When the doctor-patient relationship turns sexual. PMID- 26858354 TI - Identification of a novel stereotypic IGHV4-59/IGHJ5-encoded B-cell receptor subset expressed by various B-cell lymphomas with high affinity rheumatoid factor activity. PMID- 26858355 TI - Safety and efficacy of lenalidomide in combination with rituximab in recurrent indolent non-follicular lymphoma: final results of a phase II study conducted by the Fondazione Italiana Linfomi. PMID- 26858356 TI - The LSD1 inhibitor RN-1 recapitulates the fetal pattern of hemoglobin synthesis in baboons (P. anubis). AB - Increased fetal hemoglobin levels lessen the severity of symptoms and increase the lifespan of patients with sickle cell disease. Hydroxyurea, the only drug currently approved for the treatment of sickle cell disease, is not effective in a large proportion of patients and therefore new pharmacological agents that increase fetal hemoglobin levels have long been sought. Recent studies identifying LSD-1 as a repressor of gamma-globin expression led to experiments demonstrating that the LSD-1 inhibitor RN-1 increased gamma-globin expression in the sickle cell mouse model. Because the arrangement and developmental stage specific expression pattern of the beta-like globin genes is highly conserved between man and baboon, the baboon model remains the best predictor of activity of fetal hemoglobin-inducing agents in man. In this report, we demonstrate that RN-1 increases gamma-globin synthesis, fetal hemoglobin, and F cells to high levels in both anemic and non-anemic baboons with activity comparable to decitabine, the most potent fetal hemoglobin-inducing agent known. RN-1 not only restores high levels of fetal hemoglobin but causes the individual 5' Igamma- and 3' Vgamma-globin chains to be synthesized in the ratio characteristic of fetal development. Increased fetal hemoglobin was associated with increased levels of acetylated Histone H3, H3K4Me2, H3K4Me3, and RNA polymerase II at the gamma globin gene, and diminished gamma-globin promoter DNA methylation. RN-1 is likely to induce clinically relevant levels of fetal hemoglobin in patients with sickle cell disease, although careful titration of the dose may be required to minimize myelotoxicity. PMID- 26858357 TI - Allogeneic unrelated bone marrow transplantation from older donors results in worse prognosis in recipients with aplastic anemia. AB - Allogeneic bone marrow transplantation is an essential therapy for acquired aplastic anemia and prognosis has recently improved. However, engraftment failure and graft-versus-host disease are potential fatal complications. Various risk factors for poor prognosis have been identified, such as patient age and human leukocyte antigen disparity, but the relationship between donor age and prognosis is still unknown. Therefore, we performed a cohort study to compare the prognosis of unrelated bone marrow transplantation from younger and older donors using the registry database in Japan. We evaluated 427 patients (age 16-72 years) with aplastic anemia who underwent bone marrow transplantation from younger (<=39 years, n=281) or older (>=40 years, n=146) unrelated donors. Overall survival of the older donor group was significantly inferior to that of the younger donor group (adjusted hazard ratio 1.64; 95% confidence interval 1.15-2.35; P<0.01). The incidence of fatal infection was significantly higher in the older donor group (13.7% vs. 7.5%; P=0.03). Primary engraftment failure and acute graft versus-host disease were significantly more frequent in the older donor group (9.7% vs. 5.0%; adjusted hazard ratio 1.30; P=0.01, and 27.1% vs. 19.7%; adjusted hazard ratio 1.56; P=0.03, respectively). Acute graft-versus-host disease was related to a worse prognosis in the whole cohort. This study showed the inferiority of older donors in aplastic anemia; thus, donor age should be considered when multiple donors are available. A large-scale prospective study is warranted to establish a better donor selection algorithm for bone marrow transplantation in aplastic anemia. PMID- 26858358 TI - Pre-clinical evaluation of CD38 chimeric antigen receptor engineered T cells for the treatment of multiple myeloma. AB - Adoptive transfer of chimeric antigen receptor-transduced T cells is a promising strategy for cancer immunotherapy. The CD38 molecule, with its high expression on multiple myeloma cells, appears a suitable target for antibody therapy. Prompted by this, we used three different CD38 antibody sequences to generate second generation retroviral CD38-chimeric antigen receptor constructs with which we transduced T cells from healthy donors and multiple myeloma patients. We then evaluated the preclinical efficacy and safety of the transduced T cells. Irrespective of the donor and antibody sequence, CD38-chimeric antigen receptor transduced T cells proliferated, produced inflammatory cytokines and effectively lysed malignant cell lines and primary malignant cells from patients with acute myeloid leukemia and multi-drug resistant multiple myeloma in a cell-dose, and CD38-dependent manner, despite becoming CD38-negative during culture. CD38 chimeric antigen receptor-transduced T cells also displayed significant anti tumor effects in a xenotransplant model, in which multiple myeloma tumors were grown in a human bone marrow-like microenvironment. CD38-chimeric antigen receptor-transduced T cells also appeared to lyse the CD38(+) fractions of CD34(+) hematopoietic progenitor cells, monocytes, natural killer cells, and to a lesser extent T and B cells but did not inhibit the outgrowth of progenitor cells into various myeloid lineages and, furthermore, were effectively controllable with a caspase-9-based suicide gene. These results signify the potential importance of CD38-chimeric antigen receptor-transduced T cells as therapeutic tools for CD38(+) malignancies and warrant further efforts to diminish the undesired effects of this immunotherapy using appropriate strategies. PMID- 26858360 TI - Differential Insulitic Profiles Determine the Extent of beta-Cell Destruction and the Age at Onset of Type 1 Diabetes. AB - Type 1 diabetes (T1D) results from a T cell-mediated destruction of pancreatic beta-cells following the infiltration of leukocytes (including CD8(+), CD4(+), and CD20(+) cells) into and around pancreatic islets (insulitis). Recently, we reported that two distinct patterns of insulitis occur in patients with recent onset T1D from the U.K. and that these differ principally in the proportion of infiltrating CD20(+) B cells (designated CD20Hi and CD20Lo, respectively). We have now extended this analysis to include patients from the Network for Pancreatic Organ Donors with Diabetes (U.S.) and Diabetes Virus Detection (DiViD) study (Norway) cohorts and confirm that the two profiles of insulitis occur more widely. Moreover, we show that patients can be directly stratified according to their insulitic profile and that those receiving a diagnosis before the age of 7 years always display the CD20Hi profile. By contrast, individuals who received a diagnosis beyond the age of 13 years are uniformly defined as CD20Lo. This implies that the two forms of insulitis are differentially aggressive and that patients with a CD20Hi profile lose their beta-cells at a more rapid rate. In support of this, we also find that the proportion of residual insulin-containing islets (ICIs) increases in parallel with age at the onset of T1D. Importantly, those receiving a diagnosis in, or beyond, their teenage years retain ~40% ICIs at diagnosis, implying that a functional deficit rather than an absolute beta cell loss may be causal for disease onset in these patients. We conclude that appropriate patient stratification will be critical for correct interpretation of the outcomes of intervention therapies targeted to islet-infiltrating immune cells in T1D. PMID- 26858359 TI - Dietary Betaine Supplementation Increases Fgf21 Levels to Improve Glucose Homeostasis and Reduce Hepatic Lipid Accumulation in Mice. AB - Identifying markers of human insulin resistance may permit development of new approaches for treatment and prevention of type 2 diabetes. To this end, we analyzed the fasting plasma metabolome in metabolically characterized human volunteers across a spectrum of insulin resistance. We demonstrate that plasma betaine levels are reduced in insulin-resistant humans and correlate closely with insulin sensitivity. Moreover, betaine administration to mice with diet-induced obesity prevents the development of impaired glucose homeostasis, reduces hepatic lipid accumulation, increases white adipose oxidative capacity, and enhances whole-body energy expenditure. In parallel with these beneficial metabolic effects, betaine supplementation robustly increased hepatic and circulating fibroblast growth factor (Fgf)21 levels. Betaine administration failed to improve glucose homeostasis and liver fat content in Fgf21(-/-) mice, demonstrating that Fgf21 is necessary for betaine's beneficial effects. Together, these data indicate that dietary betaine increases Fgf21 levels to improve metabolic health in mice and suggest that betaine supplementation merits further investigation as a supplement for treatment or prevention of type 2 diabetes in humans. PMID- 26858362 TI - Pumping the breaks on B cell development. PMID- 26858361 TI - Rapamycin Blocks Induction of the Thermogenic Program in White Adipose Tissue. AB - Rapamycin extends life span in mice, yet paradoxically causes lipid dysregulation and glucose intolerance through mechanisms that remain incompletely understood. Whole-body energy balance can be influenced by beige/brite adipocytes, which are inducible by cold and other stimuli via beta-adrenergic signaling in white adipose depots. Induction of beige adipocytes is considered a promising strategy to combat obesity because of their ability to metabolize glucose and lipids, dissipating the resulting energy as heat through uncoupling protein 1. Here, we report that rapamycin blocks the ability of beta-adrenergic signaling to induce beige adipocytes and expression of thermogenic genes in white adipose depots. Rapamycin enhanced transcriptional negative feedback on the beta3-adrenergic receptor. However, thermogenic gene expression remained impaired even when the receptor was bypassed with a cell-permeable cAMP analog, revealing the existence of a second inhibitory mechanism. Accordingly, rapamycin-treated mice are cold intolerant, failing to maintain body temperature and weight when shifted to 4 degrees C. Adipocyte-specific deletion of the mTORC1 subunit Raptor recapitulated the block in beta-adrenergic signaling. Our findings demonstrate a positive role for mTORC1 in the recruitment of beige adipocytes and suggest that inhibition of beta-adrenergic signaling by rapamycin may contribute to its physiological effects. PMID- 26858363 TI - Shedding light on IL-33 in the eye. PMID- 26858364 TI - A Signaling Cascade from miR444 to RDR1 in Rice Antiviral RNA Silencing Pathway. AB - Plant RNA-DEPENDENT RNA POLYMERASE1 (RDR1) is a key component of the antiviral RNA-silencing pathway, contributing to the biogenesis of virus-derived small interfering RNAs. This enzyme also is responsible for producing virus-activated endogenous small interfering RNAs to stimulate the broad-spectrum antiviral activity through silencing host genes. The expression of RDR1 orthologs in various plants is usually induced by virus infection. However, the molecular mechanisms of activation of RDR1 expression in response to virus infection remain unknown. Here, we show that a monocot-specific microRNA, miR444, is a key factor in relaying the antiviral signaling from virus infection to OsRDR1 expression. The expression of miR444 is enhanced by infection with Rice stripe virus (RSV), and overexpression of miR444 improves rice (Oryza sativa) resistance against RSV infection accompanied by the up-regulation of OsRDR1 expression. We further show that three miR444 targets, the MIKC(C)-type MADS box proteins OsMADS23, OsMADS27a, and OsMADS57, form homodimers and heterodimers between them to repress the expression of OsRDR1 by directly binding to the CArG motifs of its promoter. Consequently, an increased level of miR444 diminishes the repressive roles of OsMADS23, OsMADS27a, and OsMADS57 on OsRDR1 transcription, thus activating the OsRDR1-dependent antiviral RNA-silencing pathway. We also show that overexpression of miR444-resistant OsMADS57 reduced OsRDR1 expression and rice resistance against RSV infection, and knockout of OsRDR1 reduced rice resistance against RSV infection. In conclusion, our results reveal a molecular cascade in the rice antiviral pathway in which miR444 and its MADS box targets directly control OsRDR1 transcription. PMID- 26858367 TI - Vaccine Discovery, Production, And Delivery. PMID- 26858365 TI - The Type II NADPH Dehydrogenase Facilitates Cyclic Electron Flow, Energy Dependent Quenching, and Chlororespiratory Metabolism during Acclimation of Chlamydomonas reinhardtii to Nitrogen Deprivation. AB - When photosynthetic organisms are deprived of nitrogen (N), the capacity to grow and assimilate carbon becomes limited, causing a decrease in the productive use of absorbed light energy and likely a rise in the cellular reduction state. Although there is a scarcity of N in many terrestrial and aquatic environments, a mechanistic understanding of how photosynthesis adjusts to low-N conditions and the enzymes/activities integral to these adjustments have not been described. In this work, we use biochemical and biophysical analyses of photoautotrophically grown wild-type and mutant strains of Chlamydomonas reinhardtii to determine the integration of electron transport pathways critical for maintaining active photosynthetic complexes even after exposure of cells to N deprivation for 3 d. Key to acclimation is the type II NADPH dehydrogenase, NDA2, which drives cyclic electron flow (CEF), chlororespiration, and the generation of an H(+) gradient across the thylakoid membranes. N deprivation elicited a doubling of the rate of NDA2-dependent CEF, with little contribution from PGR5/PGRL1-dependent CEF The H(+) gradient generated by CEF is essential to sustain nonphotochemical quenching, while an increase in the level of reduced plastoquinone would promote a state transition; both are necessary to down-regulate photosystem II activity. Moreover, stimulation of NDA2-dependent chlororespiration affords additional relief from the elevated reduction state associated with N deprivation through plastid terminal oxidase-dependent water synthesis. Overall, rerouting electrons through the NDA2 catalytic hub in response to photoautotrophic N deprivation sustains cell viability while promoting the dissipation of excess excitation energy through quenching and chlororespiratory processes. PMID- 26858368 TI - Why The Decade Of Vaccines? AB - Vaccine-preventable diseases contribute to premature mortality and morbidity for children under age five in low- and middle-income countries. The global community committed to increasing coverage of vaccines during the Decade of Vaccines, 2010 20, to save lives and avert illness in the world's poorest countries. In 2011 a collaboration of development assistance partners and governments resulted in the Global Vaccine Action Plan to provide sustainable financing and expand vaccine coverage to all children by 2020. PMID- 26858366 TI - A Developmental Switch of Gene Expression in the Barley Seed Mediated by HvVP1 (Viviparous-1) and HvGAMYB Interactions. AB - The accumulation of storage compounds in the starchy endosperm of developing cereal seeds is highly regulated at the transcriptional level. These compounds, mainly starch and proteins, are hydrolyzed upon germination to allow seedling growth. The transcription factor HvGAMYB is a master activator both in the maturation phase of seed development and upon germination, acting in combination with other transcription factors. However, the precise mechanism controlling the switch from maturation to germination programs remains unclear. We report here the identification and molecular characterization of Hordeum vulgare VIVIPAROUS1 (HvVP1), orthologous to ABA-INSENSITIVE3 from Arabidopsis thaliana HvVP1 transcripts accumulate in the endosperm and the embryo of developing seeds at early stages and in the embryo and aleurone of germinating seeds up to 24 h of imbibition. In transient expression assays, HvVP1 controls the activation of Hor2 and Amy6.4 promoters exerted by HvGAMYB. HvVP1 interacts with HvGAMYB in Saccharomyces cerevisiae and in the plant nuclei, hindering its interaction with other transcription factors involved in seed gene expression programs, like BPBF. Similarly, this interaction leads to a decrease in the DNA binding of HvGAMYB and the Barley Prolamine-Box binding Factor (BPBF) to their target sequences. Our results indicate that the HvVP1 expression pattern controls the full Hor2 expression activated by GAMYB and BPBF in the developing endosperm and the Amy6.4 activation in postgerminative reserve mobilization mediated by GAMYB. All these data demonstrate the participation of HvVP1 in antagonistic gene expression programs and support its central role as a gene expression switch during seed maturation and germination. PMID- 26858369 TI - The United States' Piecemeal Approach To Vaccine Policy. AB - In the absence of a single national policy, some states have begun taking action to strengthen vaccination requirements. PMID- 26858370 TI - Return On Investment From Childhood Immunization In Low- And Middle-Income Countries, 2011-20. AB - An analysis of return on investment can help policy makers support, optimize, and advocate for the expansion of immunization programs in the world's poorest countries. We assessed the return on investment associated with achieving projected coverage levels for vaccinations to prevent diseases related to ten antigens in ninety-four low- and middle-income countries during 2011-20, the Decade of Vaccines. We derived these estimates by using costs of vaccines, supply chains, and service delivery and their associated economic benefits. Based on the costs of illnesses averted, we estimated that projected immunizations will yield a net return about 16 times greater than costs over the decade (uncertainty range: 10-25). Using a full-income approach, which quantifies the value that people place on living longer and healthier lives, we found that net returns amounted to 44 times the costs (uncertainty range: 27-67). Across all antigens, net returns were greater than costs. But to realize the substantial positive return on investment from immunization programs, it is essential that governments and donors provide the requisite investments. PMID- 26858371 TI - When Not All That Counts Can Be Counted: Economic Evaluations And The Value Of Vaccination. AB - With vaccination efforts forced to compete for scarce resources at a time when national health budgets, global health resources, and the global donor community are facing considerable strains, advocates of vaccines have sought to better identify, measure, and articulate the value of vaccination. Critics of current analyses of the value of vaccination argue that a broader view is required, one that includes the additional economic benefits of vaccines or acknowledges the social and ethical aims advanced by vaccination programs. Much of this work has paid inadequate attention to the need to apply any expanded view of value consistently across medical interventions, to the close and complex integration of vaccination efforts with other health initiatives, and to the fact that subjectivity and judgments are present in quantitative and qualitative evidence alike. To fully realize the value of vaccination, far more attention, investment, and research are required to better understand the deliberations and decision making processes by which any kind of evidence is translated into policy. PMID- 26858372 TI - The Social Value Of Vaccination Programs: Beyond Cost-Effectiveness. AB - In the current global environment of increased strain on health care budgets, all medical interventions have to compete for funding. Cost-effectiveness analysis has become a standard method to use in estimating how much value an intervention offers relative to its costs, and it has become an influential element in decision making. However, the application of cost-effectiveness analysis to vaccination programs fails to capture the full contribution such a program offers to the community. Recent literature has highlighted how cost-effectiveness analysis can neglect the broader economic impact of vaccines. In this article we also argue that socioethical contributions such as effects on health equity, sustaining the public good of herd immunity, and social integration of minority groups are neglected in cost-effectiveness analysis. Evaluations of vaccination programs require broad and multidimensional perspectives that can account for their social, ethical, and economic impact as well as their cost-effectiveness. PMID- 26858373 TI - Vaccine Pipeline Has Grown During The Past Two Decades With More Early-Stage Trials From Small And Medium-Size Companies. AB - Many serious diseases lack safe and effective vaccines. Using a large commercial database, we examined trends in global vaccine research and development and found that the proportion of new vaccine candidates entering all stages of clinical development increased by 3-5 percentage points over the past two decades. Small and medium-size companies accounted for nearly twice as many new Phase I vaccine trials compared to large companies, but late-stage (Phase III) vaccine trials were dominated by large companies. There were no significant differences between vaccines and drugs in the probability of success in clinical trials or in profitability. Small and medium-size companies, including spin-outs from academic research centers, play an important role in innovative research and discovery. Our findings suggest that policy making targeted at smaller companies, such as prizes or opportunities for public-private partnerships, could support the development of new vaccines, particularly those targeting unmet medical needs and emerging public health threats. PMID- 26858374 TI - Current Global Pricing For Human Papillomavirus Vaccines Brings The Greatest Economic Benefits To Rich Countries. AB - Vaccinating females against human papillomavirus (HPV) prior to the debut of sexual activity is an effective way to prevent cervical cancer, yet vaccine uptake in low- and middle-income countries has been hindered by high vaccine prices. We created an economic model to estimate the distribution of the economic surplus-the sum of all health and economic benefits of a vaccine, minus the costs of development, production, and distribution-among different country income groups and manufacturers for a cohort of twelve-year-old females in 2012. We found that manufacturers may have received economic returns worth five times their original investment in HPV vaccine development. High-income countries gained the greatest economic surplus of any income category, realizing over five times more economic value per vaccinated female than low-income countries did. Subsidizing vaccine prices in low- and middle-income countries could both reduce financial barriers to vaccine adoption and still allow high-income countries to retain their economic surpluses and manufacturers to retain their profits. PMID- 26858375 TI - No Shot: US Vaccine Prices And Shortages. AB - In 2004 an Institute of Medicine report warned of vaccine shortages, raising concerns about disease outbreaks. More than a decade later, we looked for progress in reducing vaccine shortages. We analyzed data on vaccine sales and shortages reported by practitioners and patients to the Food and Drug Administration and the American Society of Health-System Pharmacists in the period 2004-13. We found that the number of annual vaccine shortages peaked in 2007, when there were shortages of seven vaccines; there were only two shortages in 2013. There were no shortages of vaccines with a mean price per dose greater than $75 during the study period. Furthermore, we found that a 10 percent increase in price was associated with a nearly 1 percent decrease in the probability of a shortage. Government payers should carefully consider the benefits of averting shortages when evaluating prices for vaccines, including older vaccines whose prices have been subject to congressional price caps. PMID- 26858376 TI - Vaccine Assistance To Low- And Middle-Income Countries Increased To $3.6 Billion In 2014. AB - In the 2012 Global Vaccine Action Plan, development assistance partners committed to providing sustainable financing for vaccines and expanding vaccination coverage to all children in low- and middle-income countries by 2020. To assess progress toward these goals, the Institute for Health Metrics and Evaluation produced estimates of development assistance for vaccinations. These estimates reveal major increases in the assistance provided since 2000. In 2014, $3.6 billion in development assistance for vaccinations was provided for low- and middle-income countries, up from $822 million in 2000. The funding increase was driven predominantly by the establishment of Gavi, the Vaccine Alliance, supported by the Bill & Melinda Gates Foundation and the governments of the United States and United Kingdom. Despite stagnation in total development assistance for health from donors from 2010 onward, development assistance for vaccination has continued to grow. PMID- 26858377 TI - Gavi's Transition Policy: Moving From Development Assistance To Domestic Financing Of Immunization Programs. AB - Gavi, the Vaccine Alliance, was created in 2000 to accelerate the introduction of new and underused vaccines in lower-income countries. The period 2000-15 was marked by the rapid uptake of new vaccines in more than seventy countries eligible for Gavi support. To stay focused on the poorest countries, Gavi's support phases out after countries' gross national income per capita surpasses a set threshold, which requires governments to assume responsibility for the continued financing of vaccines introduced with Gavi support. Gavi's funding will end in the period 2016-20 for nineteen countries that have exceeded the eligibility threshold. To avoid disrupting lifesaving immunization programs and to ensure the long-term sustainable impact of Gavi's investments, it is vital that governments succeed in transitioning from development assistance to domestic financing of immunization programs. This article discusses some of the challenges facing countries currently transitioning out of Gavi support, how Gavi's policies have evolved to help manage the risks involved in this process, and the lessons learned from this experience. PMID- 26858378 TI - EPIC Studies: Governments Finance, On Average, More Than 50 Percent Of Immunization Expenses, 2010-11. AB - Governments in resource-poor settings have traditionally relied on external donor support for immunization. Under the Global Vaccine Action Plan, adopted in 2014, countries have committed to mobilizing additional domestic resources for immunization. Data gaps make it difficult to map how well countries have done in spending government resources on immunization to demonstrate greater ownership of programs. This article presents findings of an innovative approach for financial mapping of routine immunization applied in Benin, Ghana, Honduras, Moldova, Uganda, and Zambia. This approach uses modified System of Health Accounts coding to evaluate data collected from national and subnational levels and from donor agencies. We found that government sources accounted for 27-95 percent of routine immunization financing in 2011, with countries that have higher gross national product per capita better able to finance requirements. Most financing is channeled through government agencies and used at the primary care level. Sustainable immunization programs will depend upon whether governments have the fiscal space to allocate additional resources. Ongoing robust analysis of routine immunization should be instituted within the context of total health expenditure tracking. PMID- 26858379 TI - Routes Countries Can Take To Achieve Full Ownership Of Immunization Programs. AB - A goal of the Global Vaccine Action Plan, led by the World Health Organization, is country ownership by 2020, defined here as the point when a country fully finances its routine immunization program with domestic resources. This article reports the progress made toward country ownership in twenty-two lower- and lower middle-income countries engaged in the Sabin Vaccine Institute's Sustainable Immunization Financing Program. We focus on new practices developed in the key public institutions concerned with immunization financing, budget and resource tracking, and legislation, using case studies as examples. Our analysis found that many countries are undertaking new funding mechanisms to reach financing goals. However, budget transparency remains a problem, as only eleven of the twenty-two countries have performed sequential analyses of their immunization program budgets. Promisingly, six countries (Cameroon, the Republic of the Congo, Nepal, Nigeria, Senegal, and Uganda) are creating new national immunization funding sources that are backed by legislation. Seven countries already have laws regarding immunization, and new immunization legislative projects are under way in thirteen others. PMID- 26858380 TI - Country Ownership And Gavi Transition: Comprehensive Approaches To Supporting New Vaccine Introduction. AB - Since the mid-2000s low- and lower-middle-income countries have been focusing on developing and using evidence for immunization policy making, with an increasing emphasis on cost-effectiveness analysis, program costing, and financial flows particularly for the introduction of newer, more expensive vaccines. While this is critical to informing decisions, countries still need to increase national immunization investment and explore innovative approaches to augment financing of immunization programs. The need for increased financing is especially strong in countries transitioning from support by Gavi, the Vaccine Alliance. With increased fiscal space to finance health and immunization programs as a result of improved economic performance, low- and lower-middle-income countries can reach the health status enjoyed by wealthier nations within a generation. However, new strategies and approaches related to domestic resources for immunization programs are needed to achieve this goal. Governments will need to increase their investments and modify existing external immunization financing arrangements if country ownership of immunization programs and the full promise of new vaccines are to be realized. PMID- 26858381 TI - The Global Polio Eradication Initiative: Progress, Lessons Learned, And Polio Legacy Transition Planning. AB - The world is closer than ever to achieving global polio eradication, with record low polio cases in 2015 and the impending prospect of a polio-free Africa. Tens of millions of volunteers, social mobilizers, and health workers have participated in the Global Polio Eradication Initiative. The program contributes to efforts to deliver other health benefits, including health systems strengthening. As the initiative nears completion after more than twenty-five years, it becomes critical to document and transition the knowledge, lessons learned, assets, and infrastructure accumulated by the initiative to address other health goals and priorities. The primary goals of this process, known as polio legacy transition planning, are both to protect a polio-free world and to ensure that investments in polio eradication will contribute to other health goals after polio is completely eradicated. The initiative is engaged in an extensive transition process of consultations and planning at the global, regional, and country levels. A successful completion of this process will result in a well-planned and -managed conclusion of the initiative that will secure the global public good gained by ending one of the world's most devastating diseases and ensure that these investments provide public health benefits for years to come. PMID- 26858382 TI - Assessing Interventions To Improve Influenza Vaccine Uptake Among Health Care Workers. AB - Despite official recommendations for health care workers to receive the influenza vaccine, uptake remains low. This systematic review of randomized controlled trials was conducted to understand the evidence about interventions to improve influenza vaccine uptake among health care workers. We identified twelve randomized controlled trials that, collectively, assessed six major categories of interventions involving 193,924 health care workers in high-income countries. The categories were educational materials and training sessions, improved access to the vaccine, rewards following vaccination, organized efforts to raise vaccine awareness, reminders to get vaccinated, and the use of lead advocates for vaccination. Only one of the four studies that evaluated the effect of a single intervention in isolation demonstrated a significantly higher vaccine uptake rate in the intervention group, compared to controls. However, five of the eight studies that evaluated a combination of strategies showed significantly higher vaccine uptake. Despite the low quality of the studies identified, the data suggest that combined interventions can moderately increase vaccine uptake among health care workers. Further methodologically appropriate trials of combined interventions tailored to individual health care settings and incorporating less studied strategies would enhance the evidence about interventions to improve immunization uptake among health care workers. PMID- 26858383 TI - Reorganizing Nigeria's Vaccine Supply Chain Reduces Need For Additional Storage Facilities, But More Storage Is Required. AB - One of the major problems facing Nigeria's vaccine supply chain is the lack of adequate vaccine storage facilities. Despite the introduction of solar-powered refrigerators and the use of new tools to monitor supply levels, this problem persists. Using data on vaccine supply for 2011-14 from Nigeria's National Primary Health Care Development Agency, we created a simulation model to explore the effects of variance in supply and demand on storage capacity requirements. We focused on the segment of the supply chain that moves vaccines inside Nigeria. Our findings suggest that 55 percent more vaccine storage capacity is needed than is currently available. We found that reorganizing the supply chain as proposed by the National Primary Health Care Development Agency could reduce that need to 30 percent more storage. Storage requirements varied by region of the country and vaccine type. The Nigerian government may want to consider the differences in storage requirements by region and vaccine type in its proposed reorganization efforts. PMID- 26858384 TI - Argentina's Successful Implementation Of A National Human Papillomavirus Vaccination Program. AB - Every year around fourteen million people globally are infected with human papillomavirus (HPV), the sexually transmitted virus that is the cause of most cervical cancers. A number of vaccines have been developed to protect against HPV, but in many countries, HPV vaccination rates have been low compared with rates for other recommended vaccines. Parental concerns, cost, and lack of information and awareness among both health professionals and parents are cited as important barriers to HPV vaccination. In Argentina the HPV vaccine has been provided to all eleven-year-old girls since 2011 as part of a comprehensive national program to prevent cervical cancer. Coverage increased from negligible levels before 2011 to a national average of 87.9 percent for the first dose, 71.6 percent for the second dose, and 52.2 percent for the third dose in 2013. There was a large variance in HPV vaccine coverage across the country's provinces. This article describes key strategies to overcome barriers to implementation of HPV vaccination and provides recommendations for policy makers. PMID- 26858386 TI - As Oral Vaccines Fall Short In Low-Income Countries, Researchers Look For Solutions. PMID- 26858385 TI - Strategies To Boost Maternal Immunization To Achieve Further Gains In Improved Maternal And Newborn Health. AB - Despite the indisputable successes of the United Nations Millennium Development Goals, which include goals on improving maternal health and reducing child mortality, millions of mothers and newborns still die tragically and unnecessarily each year. Many of these deaths result from vaccine-preventable diseases, since obstacles such as cost and accessibility have hampered efforts to deliver efficacious vaccines to those most in need. Additionally, many vaccines given to mothers and children under age five are not suitable for newborns, since their maturing immune systems do not respond optimally during the first few months of life. Maternal immunization-the process by which a pregnant woman's immune system is fortified against a particular disease and the protection is then transferred to her unborn child-has emerged as a strategy to prevent many unnecessary maternal and newborn deaths. We review vaccines that are already used for maternal immunization, analyze vaccines under development that could be used for maternal immunization strategies in the future, and recommend that policy makers use maternal immunization for improved maternal and newborn health. PMID- 26858388 TI - Combining Global Elimination Of Measles And Rubella With Strengthening Of Health Systems In Developing Countries. AB - Global efforts to eliminate measles and rubella can be combined with other actions to accelerate the strengthening of health systems in developing countries. However, there are several challenges standing in the way of successfully combining measles and rubella vaccination campaigns with health systems strengthening. Those challenges include the following: achieving universal vaccine coverage while integrating the initiative with other primary care strategies and developing the necessary health system resilience to confront emergencies, ensuring epidemiological and laboratory surveillance of vaccine preventable diseases, developing the human resources needed to effectively manage and implement national strategies, increasing community demand for health services, and obtaining long-term political support. We describe lessons learned from the successful elimination of measles and rubella in the Americas and elsewhere that strive to strengthen national health systems to both improve vaccine uptake and confront emerging threats. The elimination of measles and rubella provides opportunities for nations to strengthen health systems and thus to both reduce inequities and ensure national health security. PMID- 26858387 TI - Slow Progress In Finalizing Measles And Rubella Elimination In The European Region. AB - All countries in the World Health Organization European Region committed to eliminating endemic transmission of measles and rubella by 2015, and disease incidence has decreased dramatically. However, there was little progress between 2012 and 2013, and the goal will likely not be achieved on time. Genuine political commitment, increased technical capacity, and greater public awareness are urgently needed, especially in Western Europe. PMID- 26858389 TI - Exploring The Impact Of The US Measles Outbreak On Parental Awareness Of And Support For Vaccination. AB - Despite consensus among health officials that childhood immunizations are a safe and effective means of protecting people from disease, some parents remain hesitant about vaccinating their children. This hesitancy has been linked to a lack of confidence in recommended vaccinations as well as a desire to delay or further space out scheduled vaccinations but also outright refusal of vaccines. Using two national surveys of parents of children ages five and younger, collected immediately prior to and in the weeks following the 2014-15 US measles outbreak, this study examined the awareness of this vaccine-preventable disease outbreak among parents and whether awareness of the outbreak affected their beliefs about childhood vaccination, confidence, and intentions. The study found that while most parents were aware of the outbreak, many were not, and the level of familiarity mattered, particularly on measures of confidence in vaccines and support for mandates requiring childhood vaccination. Increases in vaccine related concerns were found as well, indicating that disease outbreaks foster not just awareness of vaccines and their potential to prevent disease but a range of parental responses. PMID- 26858390 TI - Publicly Available Online Tool Facilitates Real-Time Monitoring Of Vaccine Conversations And Sentiments. AB - Real-time monitoring of mainstream and social media can inform public health practitioners and policy makers about vaccine sentiment and hesitancy. We describe a publicly available platform for monitoring vaccination-related content, called the Vaccine Sentimeter. With automated data collection from 100,000 mainstream media sources and Twitter, natural-language processing for automated filtering, and manual curation to ensure accuracy, the Vaccine Sentimeter offers a global real-time view of vaccination conversations online. To assess the system's utility, we followed two events: polio vaccination in Pakistan after a news story about a Central Intelligence Agency vaccination ruse and subsequent attacks on health care workers, and a controversial episode in a television program about adverse events following human papillomavirus vaccination. For both events, increased online activity was detected and characterized. For the first event, Twitter response to the attacks on health care workers decreased drastically after the first attack, in contrast to mainstream media coverage. For the second event, the mainstream and social media response was largely positive about the HPV vaccine, but antivaccine conversations persisted longer than the provaccine reaction. Using the Vaccine Sentimeter could enable public health professionals to detect increased online activity or sudden shifts in sentiment that could affect vaccination uptake. PMID- 26858391 TI - A Tale Of Two States: Mississippi, West Virginia, And Exemptions To Compulsory School Vaccination Laws. AB - School-based compulsory vaccination laws have provoked debates over the legitimacy of government coercion versus the scope of parental rights. A key point of contention in these school vaccination laws are provisions known as exemption clauses that allow some parents to enroll their children in school unimmunized for reasons other than medical conditions. For more than three decades Mississippi and West Virginia stood apart as the only two US states that did not offer nonmedical exemptions to school vaccination laws. But other states seem to be moving in this direction, such as California, which in 2015 eliminated nonmedical exemptions following the Disneyland measles outbreak. The apparent shift creates an opportune moment to look at the experiences of Mississippi and West Virginia. Through a review of legislative histories, legal rulings, media accounts, and interviews with health officials in the two states, we consider the reasons for and consequences of their allowing only medical exemptions and the prospects their approach holds out for other states that may wish to emulate it. The experiences of these two states suggest that contrary to conventional wisdom, it may be politically tenable to limit exemptions to only medical reasons without damaging either the stature of public health or the immunization system. PMID- 26858392 TI - Since The Start Of The Vaccines For Children Program, Uptake Has Increased, And Most Disparities Have Decreased. AB - The Vaccines for Children program is a US government intervention aimed at increasing vaccination uptake by removing financial barriers that may prevent US children from accessing vaccinations. This study examined the impact that this intervention had on race and ethnicity-related and income-related disparities for diphtheria-tetanus-acellular pertussis, measles-mumps-rubella, and polio vaccinations, using data from the National Immunization Survey, 1995-2013. Vaccination rates increased across all races, ethnicities, and income groups following the introduction of the Vaccines for Children program. Disparities among race and ethnic groups narrowed considerably over time since the introduction of the vaccine program, although income-related disparities changed at different rates within racial and ethnic groups and in some cases increased. Government interventions aimed solely at reducing certain financial barriers to vaccination may fail to address other important aspects of cost or perceived benefits that influence vaccination uptake, especially among poorer children. PMID- 26858393 TI - When There's No Cure: My Brother's Battle With Drug-Resistant TB. AB - As the incidence of tuberculosis has waned, so has investment in new tests and treatments-and that may prove to be a mistake. PMID- 26858394 TI - Efforts To Improve Quality Of Care And Patient Satisfaction. PMID- 26858396 TI - Residential Care Facilities And Health Care. PMID- 26858397 TI - You Are What You Feed Your Gut Microbiome. PMID- 26858398 TI - Genetic specificity of a plant-insect food web: Implications for linking genetic variation to network complexity. AB - Theory predicts that intraspecific genetic variation can increase the complexity of an ecological network. To date, however, we are lacking empirical knowledge of the extent to which genetic variation determines the assembly of ecological networks, as well as how the gain or loss of genetic variation will affect network structure. To address this knowledge gap, we used a common garden experiment to quantify the extent to which heritable trait variation in a host plant determines the assembly of its associated insect food web (network of trophic interactions). We then used a resampling procedure to simulate the additive effects of genetic variation on overall food-web complexity. We found that trait variation among host-plant genotypes was associated with resistance to insect herbivores, which indirectly affected interactions between herbivores and their insect parasitoids. Direct and indirect genetic effects resulted in distinct compositions of trophic interactions associated with each host-plant genotype. Moreover, our simulations suggest that food-web complexity would increase by 20% over the range of genetic variation in the experimental population of host plants. Taken together, our results indicate that intraspecific genetic variation can play a key role in structuring ecological networks, which may in turn affect network persistence. PMID- 26858399 TI - Deterministically patterned biomimetic human iPSC-derived hepatic model via rapid 3D bioprinting. AB - The functional maturation and preservation of hepatic cells derived from human induced pluripotent stem cells (hiPSCs) are essential to personalized in vitro drug screening and disease study. Major liver functions are tightly linked to the 3D assembly of hepatocytes, with the supporting cell types from both endodermal and mesodermal origins in a hexagonal lobule unit. Although there are many reports on functional 2D cell differentiation, few studies have demonstrated the in vitro maturation of hiPSC-derived hepatic progenitor cells (hiPSC-HPCs) in a 3D environment that depicts the physiologically relevant cell combination and microarchitecture. The application of rapid, digital 3D bioprinting to tissue engineering has allowed 3D patterning of multiple cell types in a predefined biomimetic manner. Here we present a 3D hydrogel-based triculture model that embeds hiPSC-HPCs with human umbilical vein endothelial cells and adipose-derived stem cells in a microscale hexagonal architecture. In comparison with 2D monolayer culture and a 3D HPC-only model, our 3D triculture model shows both phenotypic and functional enhancements in the hiPSC-HPCs over weeks of in vitro culture. Specifically, we find improved morphological organization, higher liver specific gene expression levels, increased metabolic product secretion, and enhanced cytochrome P450 induction. The application of bioprinting technology in tissue engineering enables the development of a 3D biomimetic liver model that recapitulates the native liver module architecture and could be used for various applications such as early drug screening and disease modeling. PMID- 26858400 TI - Cellular softening mediates leukocyte demargination and trafficking, thereby increasing clinical blood counts. AB - Leukocytes normally marginate toward the vascular wall in large vessels and within the microvasculature. Reversal of this process, leukocyte demargination, leads to substantial increases in the clinical white blood cell and granulocyte count and is a well-documented effect of glucocorticoid and catecholamine hormones, although the underlying mechanisms remain unclear. Here we show that alterations in granulocyte mechanical properties are the driving force behind glucocorticoid- and catecholamine-induced demargination. First, we found that the proportions of granulocytes from healthy human subjects that traversed and demarginated from microfluidic models of capillary beds and veins, respectively, increased after the subjects ingested glucocorticoids. Also, we show that glucocorticoid and catecholamine exposure reorganizes cellular cortical actin, significantly reducing granulocyte stiffness, as measured with atomic force microscopy. Furthermore, using simple kinetic theory computational modeling, we found that this reduction in stiffness alone is sufficient to cause granulocyte demargination. Taken together, our findings reveal a biomechanical answer to an old hematologic question regarding how glucocorticoids and catecholamines cause leukocyte demargination. In addition, in a broader sense, we have discovered a temporally and energetically efficient mechanism in which the innate immune system can simply alter leukocyte stiffness to fine tune margination/demargination and therefore leukocyte trafficking in general. These observations have broad clinically relevant implications for the inflammatory process overall as well as hematopoietic stem cell mobilization and homing. PMID- 26858401 TI - Structure-function analysis of myomaker domains required for myoblast fusion. AB - During skeletal muscle development, myoblasts fuse to form multinucleated myofibers. Myomaker [Transmembrane protein 8c (TMEM8c)] is a muscle-specific protein that is essential for myoblast fusion and sufficient to promote fusion of fibroblasts with muscle cells; however, the structure and biochemical properties of this membrane protein have not been explored. Here, we used CRISPR/Cas9 mutagenesis to disrupt myomaker expression in the C2C12 muscle cell line, which resulted in complete blockade to fusion. To define the functional domains of myomaker required to direct fusion, we established a heterologous cell-cell fusion system, in which fibroblasts expressing mutant versions of myomaker were mixed with WT myoblasts. Our data indicate that the majority of myomaker is embedded in the plasma membrane with seven membrane-spanning regions and a required intracellular C-terminal tail. We show that myomaker function is conserved in other mammalian orthologs; however, related family members (TMEM8a and TMEM8b) do not exhibit fusogenic activity. These findings represent an important step toward deciphering the cellular components and mechanisms that control myoblast fusion and muscle formation. PMID- 26858402 TI - Topological constraints and modular structure in the folding and functional motions of GlpG, an intramembrane protease. AB - We investigate the folding of GlpG, an intramembrane protease, using perfectly funneled structure-based models that implicitly account for the absence or presence of the membrane. These two models are used to describe, respectively, folding in detergent micelles and folding within a bilayer, which effectively constrains GlpG's topology in unfolded and partially folded states. Structural free-energy landscape analysis shows that although the presence of multiple folding pathways is an intrinsic property of GlpG's modular functional architecture, the large entropic cost of organizing helical bundles in the absence of the constraining bilayer leads to pathways that backtrack (i.e., local unfolding of previously folded substructures is required when moving from the unfolded to the folded state along the minimum free-energy pathway). This backtracking explains the experimental observation of thermodynamically destabilizing mutations that accelerate GlpG's folding in detergent micelles. In contrast, backtracking is absent from the model when folding is constrained within a bilayer, the environment in which GlpG has evolved to fold. We also characterize a near-native state with a highly mobile transmembrane helix 5 (TM5) that is significantly populated under folding conditions when GlpG is embedded in a bilayer. Unbinding of TM5 from the rest of the structure exposes GlpG's active site, consistent with studies of the catalytic mechanism of GlpG that suggest that TM5 serves as a substrate gate to the active site. PMID- 26858403 TI - Inbreeding drives maize centromere evolution. AB - Functional centromeres, the chromosomal sites of spindle attachment during cell division, are marked epigenetically by the centromere-specific histone H3 variant cenH3 and typically contain long stretches of centromere-specific tandem DNA repeats (~1.8 Mb in maize). In 23 inbreds of domesticated maize chosen to represent the genetic diversity of maize germplasm, partial or nearly complete loss of the tandem DNA repeat CentC precedes 57 independent cenH3 relocation events that result in neocentromere formation. Chromosomal regions with newly acquired cenH3 are colonized by the centromere-specific retrotransposon CR2 at a rate that would result in centromere-sized CR2 clusters in 20,000-95,000 y. Three lines of evidence indicate that CentC loss is linked to inbreeding, including (i) CEN10 of temperate lineages, presumed to have experienced a genetic bottleneck, contain less CentC than their tropical relatives; (ii) strong selection for centromere-linked genes in domesticated maize reduced diversity at seven of the ten maize centromeres to only one or two postdomestication haplotypes; and (iii) the centromere with the largest number of haplotypes in domesticated maize (CEN7) has the highest CentC levels in nearly all domesticated lines. Rare recombinations introduced one (CEN2) or more (CEN5) alternate CEN haplotypes while retaining a single haplotype at domestication loci linked to these centromeres. Taken together, this evidence strongly suggests that inbreeding, favored by postdomestication selection for centromere-linked genes affecting key domestication or agricultural traits, drives replacement of the tandem centromere repeats in maize and other crop plants. Similar forces may act during speciation in natural systems. PMID- 26858404 TI - Kalirin and Trio proteins serve critical roles in excitatory synaptic transmission and LTP. AB - The molecular mechanism underlying long-term potentiation (LTP) is critical for understanding learning and memory. CaMKII, a key kinase involved in LTP, is both necessary and sufficient for LTP induction. However, how CaMKII gives rise to LTP is currently unknown. Recent studies suggest that Rho GTPases are necessary for LTP. Rho GTPases are activated by Rho guanine exchange factors (RhoGEFs), but the RhoGEF(s) required for LTP also remain unknown. Here, using a combination of molecular, electrophysiological, and imaging techniques, we show that the RhoGEF Kalirin and its paralog Trio play critical and redundant roles in excitatory synapse structure and function. Furthermore, we show that CaMKII phosphorylation of Kalirin is sufficient to enhance synaptic AMPA receptor expression, and that preventing CaMKII signaling through Kalirin and Trio prevents LTP induction. Thus, our data identify Kalirin and Trio as the elusive targets of CaMKII phosphorylation responsible for AMPA receptor up-regulation during LTP. PMID- 26858405 TI - Adaptive methylation regulation of p53 pathway in sympatric speciation of blind mole rats, Spalax. AB - Epigenetic modifications play significant roles in adaptive evolution. The tumor suppressor p53, well known for controlling cell fate and maintaining genomic stability, is much less known as a master gene in environmental adaptation involving methylation modifications. The blind subterranean mole rat Spalax eherenbergi superspecies in Israel consists of four species that speciated peripatrically. Remarkably, the northern Galilee species Spalax galili (2n = 52) underwent adaptive ecological sympatric speciation, caused by the sharply divergent chalk and basalt ecologies. This was demonstrated by mitochondrial and nuclear genomic evidence. Here we show that the expression patterns of the p53 regulatory pathway diversified between the abutting sympatric populations of S. galili in sharply divergent chalk-basalt ecologies. We identified higher methylation on several sites of the p53 promoter in the population living in chalk soil (chalk population). Site mutagenesis showed that methylation on these sites linked to the transcriptional repression of p53 involving Cut-Like Homeobox 1 (Cux1), paired box 4 (Pax 4), Pax 6, and activator protein 1 (AP-1). Diverse expression levels of p53 between the incipiently sympatrically speciating chalk basalt abutting populations of S. galili selectively affected cell-cycle arrest but not apoptosis. We hypothesize that methylation modification of p53 has adaptively shifted in supervising its target genes during sympatric speciation of S. galili to cope with the contrasting environmental stresses of the abutting divergent chalk-basalt ecologies. PMID- 26858406 TI - Structure of the Brd4 ET domain bound to a C-terminal motif from gamma-retroviral integrases reveals a conserved mechanism of interaction. AB - The bromodomain and extraterminal domain (BET) protein family are promising therapeutic targets for a range of diseases linked to transcriptional activation, cancer, viral latency, and viral integration. Tandem bromodomains selectively tether BET proteins to chromatin by engaging cognate acetylated histone marks, and the extraterminal (ET) domain is the focal point for recruiting a range of cellular and viral proteins. BET proteins guide gamma-retroviral integration to transcription start sites and enhancers through bimodal interaction with chromatin and the gamma-retroviral integrase (IN). We report the NMR-derived solution structure of the Brd4 ET domain bound to a conserved peptide sequence from the C terminus of murine leukemia virus (MLV) IN. The complex reveals a protein-protein interaction governed by the binding-coupled folding of disordered regions in both interacting partners to form a well-structured intermolecular three-stranded beta sheet. In addition, we show that a peptide comprising the ET binding motif (EBM) of MLV IN can disrupt the cognate interaction of Brd4 with NSD3, and that substitutions of Brd4 ET residues essential for binding MLV IN also impair interaction of Brd4 with a number of cellular partners involved in transcriptional regulation and chromatin remodeling. This suggests that gamma retroviruses have evolved the EBM to mimic a cognate interaction motif to achieve effective integration in host chromatin. Collectively, our findings identify key structural features of the ET domain of Brd4 that allow for interactions with both cellular and viral proteins. PMID- 26858408 TI - Genetically encoded sensors enable real-time observation of metabolite production. AB - Engineering cells to produce valuable metabolic products is hindered by the slow and laborious methods available for evaluating product concentration. Consequently, many designs go unevaluated, and the dynamics of product formation over time go unobserved. In this work, we develop a framework for observing product formation in real time without the need for sample preparation or laborious analytical methods. We use genetically encoded biosensors derived from small-molecule responsive transcription factors to provide a fluorescent readout that is proportional to the intracellular concentration of a target metabolite. Combining an appropriate biosensor with cells designed to produce a metabolic product allows us to track product formation by observing fluorescence. With individual cells exhibiting fluorescent intensities proportional to the amount of metabolite they produce, high-throughput methods can be used to rank the quality of genetic variants or production conditions. We observe production of several renewable plastic precursors with fluorescent readouts and demonstrate that higher fluorescence is indeed an indicator of higher product titer. Using fluorescence as a guide, we identify process parameters that produce 3 hydroxypropionate at 4.2 g/L, 23-fold higher than previously reported. We also report, to our knowledge, the first engineered route from glucose to acrylate, a plastic precursor with global sales of $14 billion. Finally, we monitor the production of glucarate, a replacement for environmentally damaging detergents, and muconate, a renewable precursor to polyethylene terephthalate and nylon with combined markets of $51 billion, in real time, demonstrating that our method is applicable to a wide range of molecules. PMID- 26858407 TI - Activation of RNase L is dependent on OAS3 expression during infection with diverse human viruses. AB - The 2',5'-oligoadenylate (2-5A) synthetase (OAS)-RNase L system is an IFN-induced antiviral pathway. RNase L activity depends on 2-5A, synthesized by OAS. Although all three enzymatically active OAS proteins in humans--OAS1, OAS2, and OAS3- synthesize 2-5A upon binding dsRNA, it is unclear which are responsible for RNase L activation during viral infection. We used clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease (Cas9) technology to engineer human A549-derived cell lines in which each of the OAS genes or RNase L is knocked out. Upon transfection with poly(rI):poly(rC), a synthetic surrogate for viral dsRNA, or infection with each of four viruses from different groups (West Nile virus, Sindbis virus, influenza virus, or vaccinia virus), OAS1-KO and OAS2-KO cells synthesized amounts of 2-5A similar to those synthesized in parental wild-type cells, causing RNase L activation as assessed by rRNA degradation. In contrast, OAS3-KO cells synthesized minimal 2-5A, and rRNA remained intact, similar to infected RNase L-KO cells. All four viruses replicated to higher titers in OAS3-KO or RNase L-KO A549 cells than in parental, OAS1-KO, or OAS2-KO cells, demonstrating the antiviral effects of OAS3. OAS3 displayed a higher affinity for dsRNA in intact cells than either OAS1 or OAS2, consistent with its dominant role in RNase L activation. Finally, the requirement for OAS3 as the major OAS isoform responsible for RNase L activation was not restricted to A549 cells, because OAS3-KO cells derived from two other human cell lines also were deficient in RNase L activation. PMID- 26858409 TI - Aberrant activation of canonical Notch1 signaling in the mouse uterus decreases progesterone receptor by hypermethylation and leads to infertility. AB - In mammalian reproduction, implantation is one of the most critical events. Failure of implantation and the subsequent decidualization contribute to more than 75% of pregnancy losses in women. Our laboratory has previously reported that inhibition of Notch signaling results in impaired decidualization in both women and a transgenic mouse model. In this study, we generated a Notch gain-of function transgenic mouse by conditionally overexpressing the Notch1 intracellular domain (N1ICD) in the reproductive tract driven by a progesterone receptor (Pgr) -Cre. We show that the overexpression of N1ICD in the uterus results in complete infertility as a consequence of multiple developmental and physiological defects, including the absence of uterine glands and dysregulation of progesterone and estrogen signaling by a Recombination Signal Binding Protein Jkappa-dependent signaling mechanism. We further show that the inhibition of progesterone signaling is caused by hypermethylation of its receptor Pgr by Notch1 overexpression through the transcription factor PU.1 and DNA methyltransferase 3b (Dnmt3b). We have generated a mouse model to study the consequence of increased Notch signaling in female reproduction and provide the first evidence, to our knowledge, that Notch signaling can regulate epigenetic modification of the Pgr. PMID- 26858410 TI - Crystallography captures catalytic steps in human methionine adenosyltransferase enzymes. AB - The principal methyl donor of the cell, S-adenosylmethionine (SAMe), is produced by the highly conserved family of methionine adenosyltranferases (MATs) via an ATP-driven process. These enzymes play an important role in the preservation of life, and their dysregulation has been tightly linked to liver and colon cancers. We present crystal structures of human MATalpha2 containing various bound ligands, providing a "structural movie" of the catalytic steps. High- to atomic resolution structures reveal the structural elements of the enzyme involved in utilization of the substrates methionine and adenosine and in formation of the product SAMe. MAT enzymes are also able to produce S-adenosylethionine (SAE) from substrate ethionine. Ethionine, an S-ethyl analog of the amino acid methionine, is known to induce steatosis and pancreatitis. We show that SAE occupies the active site in a manner similar to SAMe, confirming that ethionine also uses the same catalytic site to form the product SAE. PMID- 26858412 TI - Engineering super mycovirus donor strains of chestnut blight fungus by systematic disruption of multilocus vic genes. AB - Transmission of mycoviruses that attenuate virulence (hypovirulence) of pathogenic fungi is restricted by allorecognition systems operating in their fungal hosts. We report the use of systematic molecular gene disruption and classical genetics for engineering fungal hosts with superior virus transmission capabilities. Four of five diallelic virus-restricting allorecognition [vegetative incompatibility (vic)] loci were disrupted in the chestnut blight fungus Cryphonectria parasitica using an adapted Cre-loxP recombination system that allowed excision and recycling of selectable marker genes (SMGs). SMG-free, quadruple vic mutant strains representing both allelic backgrounds of the remaining vic locus were then produced through mating. In combination, these super donor strains were able to transmit hypoviruses to strains that were heteroallelic at one or all of the virus-restricting vic loci. These results demonstrate the feasibility of modulating allorecognition to engineer pathogenic fungi for more efficient transmission of virulence-attenuating mycoviruses and enhanced biological control potential. PMID- 26858411 TI - Time-coded neurotransmitter release at excitatory and inhibitory synapses. AB - Communication between neurons at chemical synapses is regulated by hundreds of different proteins that control the release of neurotransmitter that is packaged in vesicles, transported to an active zone, and released when an input spike occurs. Neurotransmitter can also be released asynchronously, that is, after a delay following the spike, or spontaneously in the absence of a stimulus. The mechanisms underlying asynchronous and spontaneous neurotransmitter release remain elusive. Here, we describe a model of the exocytotic cycle of vesicles at excitatory and inhibitory synapses that accounts for all modes of vesicle release as well as short-term synaptic plasticity (STSP). For asynchronous release, the model predicts a delayed inertial protein unbinding associated with the SNARE complex assembly immediately after vesicle priming. Experiments are proposed to test the model's molecular predictions for differential exocytosis. The simplicity of the model will also facilitate large-scale simulations of neural circuits. PMID- 26858413 TI - Structural and biochemical analysis of Bcl-2 interaction with the hepatitis B virus protein HBx. AB - HBx is a hepatitis B virus protein that is required for viral infectivity and replication. Anti-apoptotic Bcl-2 family members are thought to be among the important host targets of HBx. However, the structure and function of HBx are poorly understood and the molecular mechanism of HBx-induced carcinogenesis remains unknown. In this study, we report biochemical and structural characterization of HBx. The recombinant HBx protein contains metal ions, in particular iron and zinc. A BH3-like motif in HBx (residues 110-135) binds Bcl-2 with a dissociation constant of ~193 MUM, which is drastically lower than that for a canonical BH3 motif from Bim or Bad. Structural analysis reveals that, similar to other BH3 motifs, the BH3-like motif of HBx adopts an amphipathic alpha-helix and binds the conserved BH3-binding groove on Bcl-2. Unlike the helical Bim or Bad BH3 motif, the C-terminal portion of the bound HBx BH3-like motif has an extended conformation and makes considerably fewer interactions with Bcl-2. These observations suggest that HBx may modulate Bcl-2 function in a way that is different from that of the classical BH3-only proteins. PMID- 26858414 TI - Positive-strand RNA viruses stimulate host phosphatidylcholine synthesis at viral replication sites. AB - All positive-strand RNA viruses reorganize host intracellular membranes to assemble their viral replication complexes (VRCs); however, how these viruses modulate host lipid metabolism to accommodate such membrane proliferation and rearrangements is not well defined. We show that a significantly increased phosphatidylcholine (PC) content is associated with brome mosaic virus (BMV) replication in both natural host barley and alternate host yeast based on a lipidomic analysis. Enhanced PC levels are primarily associated with the perinuclear ER membrane, where BMV replication takes place. More specifically, BMV replication protein 1a interacts with and recruits Cho2p (choline requiring 2), a host enzyme involved in PC synthesis, to the site of viral replication. These results suggest that PC synthesized at the site of VRC assembly, not the transport of existing PC, is responsible for the enhanced accumulation. Blocking PC synthesis by deleting the CHO2 gene resulted in VRCs with wider diameters than those in wild-type cells; however, BMV replication was significantly inhibited, highlighting the critical role of PC in VRC formation and viral replication. We further show that enhanced PC levels also accumulate at the replication sites of hepatitis C virus and poliovirus, revealing a conserved feature among a group of positive-strand RNA viruses. Our work also highlights a potential broad-spectrum antiviral strategy that would disrupt PC synthesis at the sites of viral replication but would not alter cellular processes. PMID- 26858416 TI - Warning signals are under positive frequency-dependent selection in nature. AB - Positive frequency-dependent selection (FDS) is a selection regime where the fitness of a phenotype increases with its frequency, and it is thought to underlie important adaptive strategies resting on signaling and communication. However, whether and how positive FDS truly operates in nature remains unknown, which hampers our understanding of signal diversity. Here, we test for positive FDS operating on the warning color patterns of chemically defended butterflies forming multiple coexisting mimicry assemblages in the Amazon. Using malleable prey models placed in localities showing differences in the relative frequencies of warningly colored prey, we demonstrate that the efficiency of a warning signal increases steadily with its local frequency in the natural community, up to a threshold where protection stabilizes. The shape of this relationship is consistent with the direct effect of the local abundance of each warning signal on the corresponding avoidance knowledge of the local predator community. This relationship, which differs from purifying selection acting on each mimetic pattern, indicates that predator knowledge, integrated over the entire community, is saturated only for the most common warning signals. In contrast, among the well-established warning signals present in local prey assemblages, most are incompletely known to local predators and enjoy incomplete protection. This incomplete predator knowledge should generate strong benefits to life history traits that enhance warning efficiency by increasing the effective frequency of prey visible to predators. Strategies such as gregariousness or niche convergence between comimics may therefore readily evolve through their effects on predator knowledge and warning efficiency. PMID- 26858415 TI - Visualizing the origins of selfish de novo mutations in individual seminiferous tubules of human testes. AB - De novo point mutations arise predominantly in the male germline and increase in frequency with age, but it has not previously been possible to locate specific, identifiable mutations directly within the seminiferous tubules of human testes. Using microdissection of tubules exhibiting altered expression of the spermatogonial markers MAGEA4, FGFR3, and phospho-AKT, whole genome amplification, and DNA sequencing, we establish an in situ strategy for discovery and analysis of pathogenic de novo mutations. In 14 testes from men aged 39-90 y, we identified 11 distinct gain-of-function mutations in five genes (fibroblast growth factor receptors FGFR2 and FGFR3, tyrosine phosphatase PTPN11, and RAS oncogene homologs HRAS and KRAS) from 16 of 22 tubules analyzed; all mutations have known associations with severe diseases, ranging from congenital or perinatal lethal disorders to somatically acquired cancers. These results support proposed selfish selection of spermatogonial mutations affecting growth factor receptor-RAS signaling, highlight its prevalence in older men, and enable direct visualization of the microscopic anatomy of elongated mutant clones. PMID- 26858417 TI - Titin strain contributes to the Frank-Starling law of the heart by structural rearrangements of both thin- and thick-filament proteins. AB - The Frank-Starling mechanism of the heart is due, in part, to modulation of myofilament Ca(2+) sensitivity by sarcomere length (SL) [length-dependent activation (LDA)]. The molecular mechanism(s) that underlie LDA are unknown. Recent evidence has implicated the giant protein titin in this cellular process, possibly by positioning the myosin head closer to actin. To clarify the role of titin strain in LDA, we isolated myocardium from either WT or homozygous mutant (HM) rats that express a giant splice isoform of titin, and subjected the muscles to stretch from 2.0 to 2.4 MUm of SL. Upon stretch, HM compared with WT muscles displayed reduced passive force, twitch force, and myofilament LDA. Time-resolved small-angle X-ray diffraction measurements of WT twitching muscles during diastole revealed stretch-induced increases in the intensity of myosin (M2 and M6) and troponin (Tn3) reflections, as well as a reduction in cross-bridge radial spacing. Independent fluorescent probe analyses in relaxed permeabilized myocytes corroborated these findings. X-ray electron density reconstruction revealed increased mass/ordering in both thick and thin filaments. The SL-dependent changes in structure observed in WT myocardium were absent in HM myocardium. Overall, our results reveal a correlation between titin strain and the Frank Starling mechanism. The molecular basis underlying this phenomenon appears not to involve interfilament spacing or movement of myosin toward actin but, rather, sarcomere stretch-induced simultaneous structural rearrangements within both thin and thick filaments that correlate with titin strain and myofilament LDA. PMID- 26858418 TI - Variable priming of a docked synaptic vesicle. AB - The priming of a docked synaptic vesicle determines the probability of its membrane (VM) fusing with the presynaptic membrane (PM) when a nerve impulse arrives. To gain insight into the nature of priming, we searched by electron tomography for structural relationships correlated with fusion probability at active zones of axon terminals at frog neuromuscular junctions. For terminals fixed at rest, the contact area between the VM of docked vesicles and PM varied >10-fold with a normal distribution. There was no merging of the membranes. For terminals fixed during repetitive evoked synaptic transmission, the normal distribution of contact areas was shifted to the left, due in part to a decreased number of large contact areas, and there was a subpopulation of large contact areas where the membranes were hemifused, an intermediate preceding complete fusion. Thus, fusion probability of a docked vesicle is related to the extent of its VM-PM contact area. For terminals fixed 1 h after activity, the distribution of contact areas recovered to that at rest, indicating the extent of a VM-PM contact area is dynamic and in equilibrium. The extent of VM-PM contact areas in resting terminals correlated with eccentricity in vesicle shape caused by force toward the PM and with shortness of active zone material macromolecules linking vesicles to PM components, some thought to include Ca(2+) channels. We propose that priming is a variable continuum of events imposing variable fusion probability on each vesicle and is regulated by force-generating shortening of active zone material macromolecules in dynamic equilibrium. PMID- 26858420 TI - Reply to Schmid, Snyder, and Gelman and Auerbach: Correlates of the increase in white non-Hispanic midlife mortality in the 21st century. PMID- 26858419 TI - Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7. AB - The artemisinin (ART)-based antimalarials have contributed significantly to reducing global malaria deaths over the past decade, but we still do not know how they kill parasites. To gain greater insight into the potential mechanisms of ART drug action, we developed a suite of ART activity-based protein profiling probes to identify parasite protein drug targets in situ. Probes were designed to retain biological activity and alkylate the molecular target(s) of Plasmodium falciparum 3D7 parasites in situ. Proteins tagged with the ART probe can then be isolated using click chemistry before identification by liquid chromatography-MS/MS. Using these probes, we define an ART proteome that shows alkylated targets in the glycolytic, hemoglobin degradation, antioxidant defense, and protein synthesis pathways, processes essential for parasite survival. This work reveals the pleiotropic nature of the biological functions targeted by this important class of antimalarial drugs. PMID- 26858421 TI - Age-aggregation bias in mortality trends. PMID- 26858422 TI - Increased mortality for white middle-aged Americans not fully explained by causes suggested. PMID- 26858423 TI - Urban and rural divergence in mortality trends: A comment on Case and Deaton. PMID- 26858424 TI - Composition of the gut microbiota modulates the severity of malaria. AB - Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ~1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from "resistant" or "susceptible" mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden. PMID- 26858425 TI - Do geographically isolated wetlands influence landscape functions? AB - Geographically isolated wetlands (GIWs), those surrounded by uplands, exchange materials, energy, and organisms with other elements in hydrological and habitat networks, contributing to landscape functions, such as flow generation, nutrient and sediment retention, and biodiversity support. GIWs constitute most of the wetlands in many North American landscapes, provide a disproportionately large fraction of wetland edges where many functions are enhanced, and form complexes with other water bodies to create spatial and temporal heterogeneity in the timing, flow paths, and magnitude of network connectivity. These attributes signal a critical role for GIWs in sustaining a portfolio of landscape functions, but legal protections remain weak despite preferential loss from many landscapes. GIWs lack persistent surface water connections, but this condition does not imply the absence of hydrological, biogeochemical, and biological exchanges with nearby and downstream waters. Although hydrological and biogeochemical connectivity is often episodic or slow (e.g., via groundwater), hydrologic continuity and limited evaporative solute enrichment suggest both flow generation and solute and sediment retention. Similarly, whereas biological connectivity usually requires overland dispersal, numerous organisms, including many rare or threatened species, use both GIWs and downstream waters at different times or life stages, suggesting that GIWs are critical elements of landscape habitat mosaics. Indeed, weaker hydrologic connectivity with downstream waters and constrained biological connectivity with other landscape elements are precisely what enhances some GIW functions and enables others. Based on analysis of wetland geography and synthesis of wetland functions, we argue that sustaining landscape functions requires conserving the entire continuum of wetland connectivity, including GIWs. PMID- 26858426 TI - Sleep deprivation and false confessions. AB - False confession is a major contributor to the problem of wrongful convictions in the United States. Here, we provide direct evidence linking sleep deprivation and false confessions. In a procedure adapted from Kassin and Kiechel [(1996) Psychol Sci 7(3):125-128], participants completed computer tasks across multiple sessions and repeatedly received warnings that pressing the "Escape" key on their keyboard would cause the loss of study data. In their final session, participants either slept all night in laboratory bedrooms or remained awake all night. In the morning, all participants were asked to sign a statement, which summarized their activities in the laboratory and falsely alleged that they pressed the Escape key during an earlier session. After a single request, the odds of signing were 4.5 times higher for the sleep-deprived participants than for the rested participants. These findings have important implications and highlight the need for further research on factors affecting true and false confessions. PMID- 26858427 TI - Brain shape convergence in the adaptive radiation of New World monkeys. AB - Primates constitute one of the most diverse mammalian clades, and a notable feature of their diversification is the evolution of brain morphology. However, the evolutionary processes and ecological factors behind these changes are largely unknown. In this work, we investigate brain shape diversification of New World monkeys during their adaptive radiation in relation to different ecological dimensions. Our results reveal that brain diversification in this clade can be explained by invoking a model of adaptive peak shifts to unique and shared optima, defined by a multidimensional ecological niche hypothesis. Particularly, we show that the evolution of convergent brain phenotypes may be related to ecological factors associated with group size (e.g., social complexity). Together, our results highlight the complexity of brain evolution and the ecological significance of brain shape changes during the evolutionary diversification of a primate clade. PMID- 26858428 TI - Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice. AB - Sarcopenia, or skeletal muscle atrophy, is a debilitating comorbidity of many physiological and pathophysiological processes, including normal aging. There are no approved therapies for sarcopenia, but the antihypertrophic myokine myostatin is a potential therapeutic target. Here, we show that treatment of young and old mice with an anti-myostatin antibody (ATA 842) for 4 wk increased muscle mass and muscle strength in both groups. Furthermore, ATA 842 treatment also increased insulin-stimulated whole body glucose metabolism in old mice, which could be attributed to increased insulin-stimulated skeletal muscle glucose uptake as measured by a hyperinsulinemic-euglycemic clamp. Taken together, these studies provide support for pharmacological inhibition of myostatin as a potential therapeutic approach for age-related sarcopenia and metabolic disease. PMID- 26858429 TI - Pliocene reversal of late Neogene aridification. AB - The Pliocene epoch (5.3-2.6 Ma) represents the most recent geological interval in which global temperatures were several degrees warmer than today and is therefore considered our best analog for a future anthropogenic greenhouse world. However, our understanding of Pliocene climates is limited by poor age control on existing terrestrial climate archives, especially in the Southern Hemisphere, and by persistent disagreement between paleo-data and models concerning the magnitude of regional warming and/or wetting that occurred in response to increased greenhouse forcing. To address these problems, here we document the evolution of Southern Hemisphere hydroclimate from the latest Miocene to the middle Pliocene using radiometrically-dated fossil pollen records preserved in speleothems from semiarid southern Australia. These data reveal an abrupt onset of warm and wet climates early within the Pliocene, driving complete biome turnover. Pliocene warmth thus clearly represents a discrete interval which reversed a long-term trend of late Neogene cooling and aridification, rather than being simply the most recent period of greater-than-modern warmth within a continuously cooling trajectory. These findings demonstrate the importance of high-resolution chronologies to accompany paleoclimate data and also highlight the question of what initiated the sustained interval of Pliocene warmth. PMID- 26858431 TI - Measuring the value of groundwater and other forms of natural capital. AB - Valuing natural capital is fundamental to measuring sustainability. The United Nations Environment Programme, World Bank, and other agencies have called for inclusion of the value of natural capital in sustainability metrics, such as inclusive wealth. Much has been written about the importance of natural capital, but consistent, rigorous valuation approaches compatible with the pricing of traditional forms of capital have remained elusive. We present a guiding quantitative framework enabling natural capital valuation that is fully consistent with capital theory, accounts for biophysical and economic feedbacks, and can guide interdisciplinary efforts to measure sustainability. We illustrate this framework with an application to groundwater in the Kansas High Plains Aquifer, a rapidly depleting asset supporting significant food production. We develop a 10-y time series (1996-2005) of natural capital asset prices that accounts for technological, institutional, and physical changes. Kansas lost approximately $110 million per year (2005 US dollars) of capital value through groundwater withdrawal and changes in aquifer management during the decade spanning 1996-2005. This annual loss in wealth is approximately equal to the state's 2005 budget surplus, and is substantially more than investments in schools over this period. Furthermore, real investment in agricultural capital also declined over this period. Although Kansas' depletion of water wealth is substantial, it may be tractably managed through careful groundwater management and compensating investments in other natural and traditional assets. Measurement of natural capital value is required to inform management and ongoing investments in natural assets. PMID- 26858430 TI - Circadian misalignment increases cardiovascular disease risk factors in humans. AB - Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show-by using two 8-d laboratory protocols-that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8-15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-alpha levels by 3-29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk. PMID- 26858432 TI - Seasonality in human cognitive brain responses. AB - Daily variations in the environment have shaped life on Earth, with circadian cycles identified in most living organisms. Likewise, seasons correspond to annual environmental fluctuations to which organisms have adapted. However, little is known about seasonal variations in human brain physiology. We investigated annual rhythms of brain activity in a cross-sectional study of healthy young participants. They were maintained in an environment free of seasonal cues for 4.5 d, after which brain responses were assessed using functional magnetic resonance imaging (fMRI) while they performed two different cognitive tasks. Brain responses to both tasks varied significantly across seasons, but the phase of these annual rhythms was strikingly different, speaking for a complex impact of season on human brain function. For the sustained attention task, the maximum and minimum responses were located around summer and winter solstices, respectively, whereas for the working memory task, maximum and minimum responses were observed around autumn and spring equinoxes. These findings reveal previously unappreciated process-specific seasonality in human cognitive brain function that could contribute to intraindividual cognitive changes at specific times of year and changes in affective control in vulnerable populations. PMID- 26858433 TI - Vasopressin increases human risky cooperative behavior. AB - The history of humankind is an epic of cooperation, which is ubiquitous across societies and increasing in scale. Much human cooperation occurs where it is risky to cooperate for mutual benefit because successful cooperation depends on a sufficient level of cooperation by others. Here we show that arginine vasopressin (AVP), a neuropeptide that mediates complex mammalian social behaviors such as pair bonding, social recognition and aggression causally increases humans' willingness to engage in risky, mutually beneficial cooperation. In two double blind experiments, male participants received either AVP or placebo intranasally and made decisions with financial consequences in the "Stag hunt" cooperation game. AVP increases humans' willingness to cooperate. That increase is not due to an increase in the general willingness to bear risks or to altruistically help others. Using functional brain imaging, we show that, when subjects make the risky Stag choice, AVP down-regulates the BOLD signal in the left dorsolateral prefrontal cortex (dlPFC), a risk-integration region, and increases the left dlPFC functional connectivity with the ventral pallidum, an AVP receptor-rich region previously associated with AVP-mediated social reward processing in mammals. These findings show a previously unidentified causal role for AVP in social approach behavior in humans, as established by animal research. PMID- 26858434 TI - Slow dissolving of emotional distress contributes to hyperarousal. AB - The mechanisms underlying hyperarousal, the key symptom of insomnia, have remained elusive, hampering cause-targeted treatment. Recently, restless rapid eye-movement (REM) sleep emerged as a robust signature of sleep in insomnia. Given the role of REM sleep in emotion regulation, we hypothesized that restless REM sleep could interfere with the overnight resolution of emotional distress, thus contributing to accumulation of arousal. Participants (n = 1,199) completed questionnaires on insomnia severity, hyperarousal, self-conscious emotional distress, and thought-like nocturnal mentation that was validated to be a specific proxy for restless REM sleep (selective fragmentation: R = 0.57, P < 0.001; eye movement density: R = 0.46, P < 0.01) in 32 polysomnographically assessed participants. The experience of distress lasting overnight increased with insomnia severity (beta = 0.29, P < 10(-23)), whereas short-lasting distress did not (beta = -0.02, P = 0.41). Insomnia severity was associated with hyperarousal (beta = 0.47, P < 10(-63)) and with the thought-like nocturnal mentation that is specifically associated with restless REM sleep (beta = 0.31, P < 10(-26)). Structural equation modeling showed that 62.4% of the association between these key characteristics of insomnia was mediated specifically by reduced overnight resolution of emotional distress. The model outperformed all alternative mediation pathways. The findings suggest that restless REM sleep reflects a process that interferes with the overnight resolution of distress. Its accumulation may promote the development of chronic hyperarousal, giving clinical relevance to the role of REM sleep in emotion regulation in insomnia, depression, and posttraumatic stress disorder. PMID- 26858435 TI - Ultrasensitive microchip based on smart microgel for real-time online detection of trace threat analytes. AB - Real-time online detection of trace threat analytes is critical for global sustainability, whereas the key challenge is how to efficiently convert and amplify analyte signals into simple readouts. Here we report an ultrasensitive microfluidic platform incorporated with smart microgel for real-time online detection of trace threat analytes. The microgel can swell responding to specific stimulus in flowing solution, resulting in efficient conversion of the stimulus signal into significantly amplified signal of flow-rate change; thus highly sensitive, fast, and selective detection can be achieved. We demonstrate this by incorporating ion-recognizable microgel for detecting trace Pb(2+), and connecting our platform with pipelines of tap water and wastewater for real-time online Pb(2+) detection to achieve timely pollution warning and terminating. This work provides a generalizable platform for incorporating myriad stimuli responsive microgels to achieve ever-better performance for real-time online detection of various trace threat molecules, and may expand the scope of applications of detection techniques. PMID- 26858437 TI - Exceptionally strong easterly wind burst stalling El Nino of 2014. AB - Intraseasonal wind bursts in the tropical Pacific are believed to affect the evolution and diversity of El Nino events. In particular, the occurrence of two strong westerly wind bursts (WWBs) in early 2014 apparently pushed the ocean atmosphere system toward a moderate to strong El Nino--potentially an extreme event according to some climate models. However, the event's progression quickly stalled, and the warming remained very weak throughout the year. Here, we find that the occurrence of an unusually strong basin-wide easterly wind burst (EWB) in June was a key factor that impeded the El Nino development. It was shortly after this EWB that all major Nino indices fell rapidly to near-normal values; a modest growth resumed only later in the year. The easterly burst and the weakness of subsequent WWBs resulted in the persistence of two separate warming centers in the central and eastern equatorial Pacific, suppressing the positive Bjerknes feedback critical for El Nino. Experiments with a climate model with superimposed wind bursts support these conclusions, pointing to inherent limits in El Nino predictability. Furthermore, we show that the spatial structure of the easterly burst matches that of the observed decadal trend in wind stress in the tropical Pacific, suggesting potential links between intraseasonal wind bursts and decadal climate variations. PMID- 26858436 TI - Respiratory virus transmission dynamics determine timing of asthma exacerbation peaks: Evidence from a population-level model. AB - Asthma exacerbations exhibit a consistent annual pattern, closely mirroring the school calendar. Although respiratory viruses--the "common cold" viruses--are implicated as a principal cause, there is little evidence to link viral prevalence to seasonal differences in risk. We jointly fit a common cold transmission model and a model of biological and environmental exacerbation triggers to estimate effects on hospitalization risk. Asthma hospitalization rate, influenza prevalence, and air quality measures are available, but common cold circulation is not; therefore, we generate estimates of viral prevalence using a transmission model. Our deterministic multivirus transmission model includes transmission rates that vary when school is closed. We jointly fit the two models to 7 y of daily asthma hospitalizations in adults and children (66,000 events) in eight metropolitan areas. For children, we find that daily viral prevalence is the strongest predictor of asthma hospitalizations, with transmission reduced by 45% (95% credible interval =41-49%) during school closures. We detect a transient period of nonspecific immunity between infections lasting 19 (17-21) d. For adults, hospitalizations are more variable, with influenza driving wintertime peaks. Neither particulate matter nor ozone was an important predictor, perhaps because of the large geographic area of the populations. The school calendar clearly and predictably drives seasonal variation in common cold prevalence, which results in the "back-to-school" asthma exacerbation pattern seen in children and indirectly contributes to exacerbation risk in adults. This study provides a framework for anticipating the seasonal dynamics of common colds and the associated risks for asthmatics. PMID- 26858438 TI - Isotopic evidence for primordial molecular cloud material in metal-rich carbonaceous chondrites. AB - The short-lived (26)Al radionuclide is thought to have been admixed into the initially (26)Al-poor protosolar molecular cloud before or contemporaneously with its collapse. Bulk inner Solar System reservoirs record positively correlated variability in mass-independent (54)Cr and (26)Mg*, the decay product of (26)Al. This correlation is interpreted as reflecting progressive thermal processing of in-falling (26)Al-rich molecular cloud material in the inner Solar System. The thermally unprocessed molecular cloud matter reflecting the nucleosynthetic makeup of the molecular cloud before the last addition of stellar-derived (26)Al has not been identified yet but may be preserved in planetesimals that accreted in the outer Solar System. We show that metal-rich carbonaceous chondrites and their components have a unique isotopic signature extending from an inner Solar System composition toward a (26)Mg*-depleted and (54)Cr-enriched component. This composition is consistent with that expected for thermally unprocessed primordial molecular cloud material before its pollution by stellar-derived (26)Al. The (26)Mg* and (54)Cr compositions of bulk metal-rich chondrites require significant amounts (25-50%) of primordial molecular cloud matter in their precursor material. Given that such high fractions of primordial molecular cloud material are expected to survive only in the outer Solar System, we infer that, similarly to cometary bodies, metal-rich carbonaceous chondrites are samples of planetesimals that accreted beyond the orbits of the gas giants. The lack of evidence for this material in other chondrite groups requires isolation from the outer Solar System, possibly by the opening of disk gaps from the early formation of gas giants. PMID- 26858439 TI - Self-targeting of TNF-releasing cancer cells in preclinical models of primary and metastatic tumors. AB - Circulating cancer cells can putatively colonize distant organs to form metastases or to reinfiltrate primary tumors themselves through a process termed "tumor self-seeding." Here we exploit this biological attribute to deliver tumor necrosis factor alpha (TNF), a potent antitumor cytokine, directly to primary and metastatic tumors in a mechanism that we have defined as "tumor self-targeting." For this purpose, we genetically engineered mouse mammary adenocarcinoma (TSA), melanoma (B16-F10), and Lewis lung carcinoma cells to produce and release murine TNF. In a series of intervention trials, systemic administration of TNF expressing tumor cells was associated with reduced growth of both primary tumors and metastatic colonies in immunocompetent mice. We show that these malignant cells home to tumors, locally release TNF, damage neovascular endothelium, and induce massive cancer cell apoptosis. We also demonstrate that such tumor-cell mediated delivery avoids or minimizes common side effects often associated with TNF-based therapy, such as acute inflammation and weight loss. Our study provides proof of concept that genetically modified circulating tumor cells may serve as targeted vectors to deliver anticancer agents. In a clinical context, this unique paradigm represents a personalized approach to be translated into applications potentially using patient-derived circulating tumor cells as self-targeted vectors for drug delivery. PMID- 26858440 TI - Effective treatment of steatosis and steatohepatitis by fibroblast growth factor 1 in mouse models of nonalcoholic fatty liver disease. AB - Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder and is strongly associated with obesity and type 2 diabetes. Currently, there is no approved pharmacological treatment for this disease, but improvement of insulin resistance using peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists, such as thiazolidinediones (TZDs), has been shown to reduce steatosis and steatohepatitis effectively and to improve liver function in patients with obesity-related NAFLD. However, this approach is limited by adverse effects of TZDs. Recently, we have identified fibroblast growth factor 1 (FGF1) as a target of nuclear receptor PPARgamma in visceral adipose tissue and as a critical factor in adipose remodeling. Because FGF1 is situated downstream of PPARgamma, it is likely that therapeutic targeting of the FGF1 pathway will eliminate some of the serious adverse effects associated with TZDs. Here we show that pharmacological administration of recombinant FGF1 (rFGF1) effectively improves hepatic inflammation and damage in leptin-deficient ob/ob mice and in choline-deficient mice, two etiologically different models of NAFLD. Hepatic steatosis was effectively reduced only in ob/ob mice, suggesting that rFGF1 stimulates hepatic lipid catabolism. Potentially adverse effects such as fibrosis or proliferation were not observed in these models. Because the anti-inflammatory effects were observed in both the presence and absence of the antisteatotic effects, our findings further suggest that the anti-inflammatory property of rFGF1 is independent of its effect on lipid catabolism. Our current findings indicate that, in addition to its potent glucose-lowering and insulin-sensitizing effects, rFGF1 could be therapeutically effective in the treatment of NAFLD. PMID- 26858441 TI - Cortical response to categorical color perception in infants investigated by near infrared spectroscopy. AB - Perceptual color space is continuous; however, we tend to divide it into only a small number of categories. It is unclear whether categorical color perception is obtained solely through the development of the visual system or whether it is affected by language acquisition. To address this issue, we recruited prelinguistic infants (5- to 7-mo-olds) to measure changes in brain activity in relation to categorical color differences by using near-infrared spectroscopy (NIRS). We presented two sets of geometric figures to infants: One set altered in color between green and blue, and the other set altered between two different shades of green. We found a significant increase in hemodynamic responses during the between-category alternations, but not during the within-category alternations. These differences in hemodynamic response based on categorical relationship were observed only in the bilateral occipitotemporal regions, and not in the occipital region. We confirmed that categorical color differences yield behavioral differences in infants. We also observed comparable hemodynamic responses to categorical color differences in adults. The present study provided the first evidence, to our knowledge, that colors of different categories are represented differently in the visual cortex of prelinguistic infants, which implies that color categories may develop independently before language acquisition. PMID- 26858442 TI - Clonally expanded CD4+ T cells can produce infectious HIV-1 in vivo. AB - Reservoirs of infectious HIV-1 persist despite years of combination antiretroviral therapy and make curing HIV-1 infections a major challenge. Most of the proviral DNA resides in CD4(+)T cells. Some of these CD4(+)T cells are clonally expanded; most of the proviruses are defective. It is not known if any of the clonally expanded cells carry replication-competent proviruses. We report that a highly expanded CD4(+) T-cell clone contains an intact provirus. The highly expanded clone produced infectious virus that was detected as persistent plasma viremia during cART in an HIV-1-infected patient who had squamous cell cancer. Cells containing the intact provirus were widely distributed and significantly enriched in cancer metastases. These results show that clonally expanded CD4(+)T cells can be a reservoir of infectious HIV-1. PMID- 26858443 TI - Cockroaches traverse crevices, crawl rapidly in confined spaces, and inspire a soft, legged robot. AB - Jointed exoskeletons permit rapid appendage-driven locomotion but retain the soft bodied, shape-changing ability to explore confined environments. We challenged cockroaches with horizontal crevices smaller than a quarter of their standing body height. Cockroaches rapidly traversed crevices in 300-800 ms by compressing their body 40-60%. High-speed videography revealed crevice negotiation to be a complex, discontinuous maneuver. After traversing horizontal crevices to enter a vertically confined space, cockroaches crawled at velocities approaching 60 cm?s( 1), despite body compression and postural changes. Running velocity, stride length, and stride period only decreased at the smallest crevice height (4 mm), whereas slipping and the probability of zigzag paths increased. To explain confined-space running performance limits, we altered ceiling and ground friction. Increased ceiling friction decreased velocity by decreasing stride length and increasing slipping. Increased ground friction resulted in velocity and stride length attaining a maximum at intermediate friction levels. These data support a model of an unexplored mode of locomotion--"body-friction legged crawling" with body drag, friction-dominated leg thrust, but no media flow as in air, water, or sand. To define the limits of body compression in confined spaces, we conducted dynamic compressive cycle tests on living animals. Exoskeletal strength allowed cockroaches to withstand forces 300 times body weight when traversing the smallest crevices and up to nearly 900 times body weight without injury. Cockroach exoskeletons provided biological inspiration for the manufacture of an origami-style, soft, legged robot that can locomote rapidly in both open and confined spaces. PMID- 26858445 TI - Correction to Supporting Information for Alessi et al., Casein kinase II promotes target silencing by miRISC through direct phosphorylation of the DEAD-box RNA helicase CGH-1. PMID- 26858446 TI - Microstructure provides insights into evolutionary design and resilience of Coscinodiscus sp. frustule. AB - We conducted in situ three-point bending experiments on beams with roughly square cross-sections, which we fabricated from the frustule of Coscinodiscus sp. We observe failure by brittle fracture at an average stress of 1.1 GPa. Analysis of crack propagation and shell morphology reveals a differentiation in the function of the frustule layers with the basal layer pores, which deflect crack propagation. We calculated the relative density of the frustule to be ~30% and show that at this density the frustule has the highest strength-to-density ratio of 1,702 kN?m/kg, a significant departure from all reported biologic materials. We also performed nanoindentation on both the single basal layer of the frustule as well as the girdle band and show that these components display similar mechanical properties that also agree well with bending tests. Transmission electron microscopy analysis reveals that the frustule is made almost entirely of amorphous silica with a nanocrystalline proximal layer. No flaws are observed within the frustule material down to 2 nm. Finite element simulations of the three-point bending experiments show that the basal layer carries most of the applied load whereas stresses within the cribrum and areolae layer are an order of magnitude lower. These results demonstrate the natural development of architecture in live organisms to simultaneously achieve light weight, strength, and exceptional structural integrity and may provide insight into evolutionary design. PMID- 26858444 TI - Ribosome Protein L4 is essential for Epstein-Barr Virus Nuclear Antigen 1 function. AB - Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1)-mediated origin of plasmid replication (oriP) DNA episome maintenance is essential for EBV-mediated tumorigenesis. We have now found that EBNA1 binds to Ribosome Protein L4 (RPL4). RPL4 shRNA knockdown decreased EBNA1 activation of an oriP luciferase reporter, EBNA1 DNA binding in lymphoblastoid cell lines, and EBV genome number per lymphoblastoid cell line. EBV infection increased RPL4 expression and redistributed RPL4 to cell nuclei. RPL4 and Nucleolin (NCL) were a scaffold for an EBNA1-induced oriP complex. The RPL4 N terminus cooperated with NCL-K429 to support EBNA1 and oriP-mediated episome binding and maintenance, whereas the NCL C-terminal K380 and K393 induced oriP DNA H3K4me2 modification and promoted EBNA1 activation of oriP-dependent transcription. These observations provide new insights into the mechanisms by which EBV uses NCL and RPL4 to establish persistent B-lymphoblastoid cell infection. PMID- 26858447 TI - Territories of heterologous inputs onto Purkinje cell dendrites are segregated by mGluR1-dependent parallel fiber synapse elimination. AB - In Purkinje cells (PCs) of the cerebellum, a single "winner" climbing fiber (CF) monopolizes proximal dendrites, whereas hundreds of thousands of parallel fibers (PFs) innervate distal dendrites, and both CF and PF inputs innervate a narrow intermediate domain. It is unclear how this segregated CF and PF innervation is established on PC dendrites. Through reconstruction of dendritic innervation by serial electron microscopy, we show that from postnatal day 9-15 in mice, both CF and PF innervation territories vigorously expand because of an enlargement of the region of overlapping innervation. From postnatal day 15 onwards, segregation of these territories occurs with robust shortening of the overlapping proximal region. Thus, innervation territories by the heterologous inputs are refined during the early postnatal period. Intriguingly, this transition is arrested in mutant mice lacking the type 1 metabotropic glutamate receptor (mGluR1) or protein kinase Cgamma (PKCgamma), resulting in the persistence of an abnormally expanded overlapping region. This arrested territory refinement is rescued by lentivirus-mediated expression of mGluR1alpha into mGluR1-deficient PCs. At the proximal dendrite of rescued PCs, PF synapses are eliminated and free spines emerge instead, whereas the number and density of CF synapses are unchanged. Because the mGluR1-PKCgamma signaling pathway is also essential for the late phase of CF synapse elimination, this signaling pathway promotes the two key features of excitatory synaptic wiring in PCs, namely CF monoinnervation by eliminating redundant CF synapses from the soma, and segregated territories of CF and PF innervation by eliminating competing PF synapses from proximal dendrites. PMID- 26858448 TI - Iontophoretic device delivery for the localized treatment of pancreatic ductal adenocarcinoma. AB - Poor delivery and systemic toxicity of many cytotoxic agents, such as the recent promising combination chemotherapy regimen of folinic acid (leucovorin), fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX), restrict their full utility in the treatment of pancreatic cancer. Local delivery of chemotherapies has become possible using iontophoretic devices that are implanted directly onto pancreatic tumors. We have fabricated implantable iontophoretic devices and tested the local iontophoretic delivery of FOLFIRINOX for the treatment of pancreatic cancer in an orthotopic patient-derived xenograft model. Iontophoretic delivery of FOLFIRINOX was found to increase tumor exposure by almost an order of magnitude compared with i.v. delivery with substantially lower plasma concentrations. Mice treated for 7 wk with device FOLFIRINOX experienced significantly greater tumor growth inhibition compared with i.v. FOLFIRINOX. A marker of cell proliferation, Ki-67, was stained, showing a significant reduction in tumor cell proliferation. These data capitalize on the unique ability of an implantable iontophoretic device to deliver much higher concentrations of drug to the tumor compared with i.v. delivery. Local iontophoretic delivery of cytotoxic agents should be considered for the treatment of patients with unresectable nonmetastatic disease and for patients with the need for palliation of local symptoms, and may be considered as a neoadjuvant approach to improve resection rates and outcome in patients with localized and locally advanced pancreatic cancer. PMID- 26858450 TI - Mesoscale texture of cement hydrates. AB - Strength and other mechanical properties of cement and concrete rely upon the formation of calcium-silicate-hydrates (C-S-H) during cement hydration. Controlling structure and properties of the C-S-H phase is a challenge, due to the complexity of this hydration product and of the mechanisms that drive its precipitation from the ionic solution upon dissolution of cement grains in water. Departing from traditional models mostly focused on length scales above the micrometer, recent research addressed the molecular structure of C-S-H. However, small-angle neutron scattering, electron-microscopy imaging, and nanoindentation experiments suggest that its mesoscale organization, extending over hundreds of nanometers, may be more important. Here we unveil the C-S-H mesoscale texture, a crucial step to connect the fundamental scales to the macroscale of engineering properties. We use simulations that combine information of the nanoscale building units of C-S-H and their effective interactions, obtained from atomistic simulations and experiments, into a statistical physics framework for aggregating nanoparticles. We compute small-angle scattering intensities, pore size distributions, specific surface area, local densities, indentation modulus, and hardness of the material, providing quantitative understanding of different experimental investigations. Our results provide insight into how the heterogeneities developed during the early stages of hydration persist in the structure of C-S-H and impact the mechanical performance of the hardened cement paste. Unraveling such links in cement hydrates can be groundbreaking and controlling them can be the key to smarter mix designs of cementitious materials. PMID- 26858449 TI - A glutamate/aspartate switch controls product specificity in a protein arginine methyltransferase. AB - Trypanosoma brucei PRMT7 (TbPRMT7) is a protein arginine methyltransferase (PRMT) that strictly monomethylates various substrates, thus classifying it as a type III PRMT. However, the molecular basis of its unique product specificity has remained elusive. Here, we present the structure of TbPRMT7 in complex with its cofactor product S-adenosyl-l-homocysteine (AdoHcy) at 2.8 A resolution and identify a glutamate residue critical for its monomethylation behavior. TbPRMT7 comprises the conserved methyltransferase and beta-barrel domains, an N-terminal extension, and a dimerization arm. The active site at the interface of the N terminal extension, methyltransferase, and beta-barrel domains is stabilized by the dimerization arm of the neighboring protomer, providing a structural basis for dimerization as a prerequisite for catalytic activity. Mutagenesis of active site residues highlights the importance of Glu181, the second of the two invariant glutamate residues of the double E loop that coordinate the target arginine in substrate peptides/proteins and that increase its nucleophilicity. Strikingly, mutation of Glu181 to aspartate converts TbPRMT7 into a type I PRMT, producing asymmetric dimethylarginine (ADMA). Isothermal titration calorimetry (ITC) using a histone H4 peptide showed that the Glu181Asp mutant has markedly increased affinity for monomethylated peptide with respect to the WT, suggesting that the enlarged active site can favorably accommodate monomethylated peptide and provide sufficient space for ADMA formation. In conclusion, these findings yield valuable insights into the product specificity and the catalytic mechanism of protein arginine methyltransferases and have important implications for the rational (re)design of PRMTs. PMID- 26858451 TI - Translation quality control is critical for bacterial responses to amino acid stress. AB - Gene expression relies on quality control for accurate transmission of genetic information. One mechanism that prevents amino acid misincorporation errors during translation is editing of misacylated tRNAs by aminoacyl-tRNA synthetases. In the absence of editing, growth is limited upon exposure to excess noncognate amino acid substrates and other stresses, but whether these physiological effects result solely from mistranslation remains unclear. To explore if translation quality control influences cellular processes other than protein synthesis, an Escherichia coli strain defective in Tyr-tRNA(Phe) editing was used. In the absence of editing, cellular levels of aminoacylated tRNA(Phe) were elevated during amino acid stress, whereas in the wild-type strain these levels declined under the same growth conditions. In the editing-defective strain, increased levels of aminoacylated tRNA(Phe) led to continued synthesis of the PheL leader peptide and attenuation of pheA transcription under amino acid stress. Consequently, in the absence of editing, activation of the phenylalanine biosynthetic operon becomes less responsive to phenylalanine limitation. In addition to raising aminoacylated tRNA levels, the absence of editing lowered the amount of deacylated tRNA(Phe) in the cell. This reduction in deacylated tRNA was accompanied by decreased synthesis of the second messenger guanosine tetraphosphate and limited induction of stringent response-dependent gene expression in editing-defective cells during amino acid stress. These data show that a single quality-control mechanism, the editing of misacylated aminoacyl tRNAs, provides a critical checkpoint both for maintaining the accuracy of translation and for determining the sensitivity of transcriptional responses to amino acid stress. PMID- 26858452 TI - A critical role for alternative polyadenylation factor CPSF6 in targeting HIV-1 integration to transcriptionally active chromatin. AB - Integration is vital to retroviral replication and influences the establishment of the latent HIV reservoir. HIV-1 integration favors active genes, which is in part determined by the interaction between integrase and lens epithelium-derived growth factor (LEDGF)/p75. Because gene targeting remains significantly enriched, relative to random in LEDGF/p75 deficient cells, other host factors likely contribute to gene-tropic integration. Nucleoporins 153 and 358, which bind HIV-1 capsid, play comparatively minor roles in integration targeting, but the influence of another capsid binding protein, cleavage and polyadenylation specificity factor 6 (CPSF6), has not been reported. In this study we knocked down or knocked out CPSF6 in parallel or in tandem with LEDGF/p75. CPSF6 knockout changed viral infectivity kinetics, decreased proviral formation, and preferentially decreased integration into transcriptionally active genes, spliced genes, and regions of chromatin enriched in genes and activating histone modifications. LEDGF/p75 depletion by contrast preferentially altered positional integration targeting within gene bodies. Dual factor knockout reduced integration into genes to below the levels observed with either single knockout and revealed that CPSF6 played a more dominant role than LEDGF/p75 in directing integration to euchromatin. CPSF6 complementation rescued HIV-1 integration site distribution in CPSF6 knockout cells, but complementation with a capsid binding mutant of CPSF6 did not. We conclude that integration targeting proceeds via two distinct mechanisms: capsid-CPSF6 binding directs HIV-1 to actively transcribed euchromatin, where the integrase-LEDGF/p75 interaction drives integration into gene bodies. PMID- 26858454 TI - High Elmo1 expression aggravates and low Elmo1 expression prevents diabetic nephropathy. AB - Human genome-wide association studies have demonstrated that polymorphisms in the engulfment and cell motility protein 1 gene (ELMO1) are strongly associated with susceptibility to diabetic nephropathy. However, proof of causation is lacking. To test whether modest changes in its expression alter the severity of the renal phenotype in diabetic mice, we have generated mice that are type 1 diabetic because they have the Ins2(Akita) gene, and also have genetically graded expression of Elmo1 in all tissues ranging in five steps from ~30% to ~200% normal. We here show that the Elmo1 hypermorphs have albuminuria, glomerulosclerosis, and changes in the ultrastructure of the glomerular basement membrane that increase in severity in parallel with the expression of Elmo 1. Progressive changes in renal mRNA expression of transforming growth factor beta1 (TGFbeta1), endothelin-1, and NAD(P)H oxidase 4 also occur in parallel with Elmo1, as do the plasma levels of cystatin C, lipid peroxides, and TGFbeta1, and erythrocyte levels of reduced glutathione. In contrast, Akita type 1 diabetic mice with below-normal Elmo1 expression have reduced expression of these various factors and less severe diabetic complications. Remarkably, the reduced Elmo1 expression in the 30% hypomorphs almost abolishes the pathological features of diabetic nephropathy, although it does not affect the hyperglycemia caused by the Akita mutation. Thus, ELMO1 plays an important role in the development of type 1 diabetic nephropathy, and its inhibition could be a promising option for slowing or preventing progression of the condition to end-stage renal disease. PMID- 26858453 TI - Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. AB - Extracellular vesicles (EVs) have become the focus of rising interest because of their numerous functions in physiology and pathology. Cells release heterogeneous vesicles of different sizes and intracellular origins, including small EVs formed inside endosomal compartments (i.e., exosomes) and EVs of various sizes budding from the plasma membrane. Specific markers for the analysis and isolation of different EV populations are missing, imposing important limitations to understanding EV functions. Here, EVs from human dendritic cells were first separated by their sedimentation speed, and then either by their behavior upon upward floatation into iodixanol gradients or by immuno-isolation. Extensive quantitative proteomic analysis allowing comparison of the isolated populations showed that several classically used exosome markers, like major histocompatibility complex, flotillin, and heat-shock 70-kDa proteins, are similarly present in all EVs. We identified proteins specifically enriched in small EVs, and define a set of five protein categories displaying different relative abundance in distinct EV populations. We demonstrate the presence of exosomal and nonexosomal subpopulations within small EVs, and propose their differential separation by immuno-isolation using either CD63, CD81, or CD9. Our work thus provides guidelines to define subtypes of EVs for future functional studies. PMID- 26858455 TI - Pathophysiological implication of CaV3.1 T-type Ca2+ channels in trigeminal neuropathic pain. AB - A crucial pathophysiological issue concerning central neuropathic pain is the modification of sensory processing by abnormally increased low-frequency brain rhythms. Here we explore the molecular mechanisms responsible for such abnormal rhythmicity and its relation to neuropathic pain syndrome. Toward this aim, we investigated the behavioral and electrophysiological consequences of trigeminal neuropathic pain following infraorbital nerve ligations in CaV3.1 T-type Ca(2+) channel knockout and wild-type mice. CaV3.1 knockout mice had decreased mechanical hypersensitivity and reduced low-frequency rhythms in the primary somatosensory cortex and related thalamic nuclei than wild-type mice. Lateral inhibition of gamma rhythm in primary somatosensory cortex layer 4, reflecting intact sensory contrast, was present in knockout mice but severely impaired in wild-type mice. Moreover, cross-frequency coupling between low-frequency and gamma rhythms, which may serve in sensory processing, was pronounced in wild-type mice but not in CaV3.1 knockout mice. Our results suggest that the presence of CaV3.1 channels is a key element in the pathophysiology of trigeminal neuropathic pain. PMID- 26858456 TI - Endocytosis separates EGF receptors from endogenous fluorescently labeled HRas and diminishes receptor signaling to MAP kinases in endosomes. AB - Signaling from epidermal growth factor receptor (EGFR) to extracellular-stimuli regulated protein kinase 1/2 (ERK1/2) is proposed to be transduced not only from the cell surface but also from endosomes, although the role of endocytosis in this signaling pathway is controversial. Ras is the only membrane-anchored component in the EGFR-ERK signaling axis, and therefore, its location determines intracellular sites of downstream signaling. Hence, we labeled endogenous H-Ras (HRas) with mVenus fluorescent protein using gene editing in HeLa cells. mVenus HRas was primarily located at the plasma membrane, and in small amounts in tubular recycling endosomes and associated vesicles. EGF stimulation resulted in fast but transient activation of mVenus-HRas. Although EGF:EGFR complexes were rapidly accumulated in endosomes together with the Grb2 adaptor, very little, if any, mVenus-HRas was detected in these endosomes. Interestingly, the activities of MEK1/2 and ERK1/2 remained high beyond the point of the physical separation of HRas from EGF:EGFR complexes and down-regulation of Ras activity. Paradoxically, this sustained MEK1/2 and ERK1/2 activation was dependent on the active EGFR kinase. Cell surface biotinylation and selective inactivation of surface EGFRs suggested that a small fraction of active EGFRs remaining in the plasma membrane is responsible for continuous signaling to MEK1/2 and ERK1/2. We propose that, under physiological conditions of cell stimulation, EGFR endocytosis serves to spatially separate EGFR-Grb2 complexes and Ras, thus terminating Ras-mediated signaling. However, sustained minimal activation of Ras by a small pool of active EGFRs in the plasma membrane is sufficient for extending MEK1/2 and ERK1/2 activities. PMID- 26858457 TI - Membrane translocation of TRPC6 channels and endothelial migration are regulated by calmodulin and PI3 kinase activation. AB - Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical transient receptor potential 6 (TRPC6) channels leading to inhibition of endothelial cell (EC) migration in vitro and delayed EC healing of arterial injuries in vivo. The precise mechanism through which lysoPC activates TRPC6 channels is not known, but calmodulin (CaM) contributes to the regulation of TRPC channels. Using site-directed mutagenesis, cDNAs were generated in which Tyr(99) or Tyr(138) of CaM was replaced with Phe, generating mutant CaM, Phe(99)-CaM, or Phe(138)-CaM, respectively. In ECs transiently transfected with pcDNA3.1-myc-His Phe(99)-CaM, but not in ECs transfected with pcDNA3.1-myc-His-Phe(138)-CaM, the lysoPC-induced TRPC6-CaM dissociation and TRPC6 externalization was disrupted. Also, the lysoPC-induced increase in intracellular calcium concentration was inhibited in ECs transiently transfected with pcDNA3.1-myc-His-Phe(99)-CaM. Blocking phosphorylation of CaM at Tyr(99) also reduced CaM association with the p85 subunit and subsequent activation of phosphatidylinositol 3-kinase (PI3K). This prevented the increase in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and the translocation of TRPC6 to the cell membrane and reduced the inhibition of EC migration by lysoPC. These findings suggest that lysoPC induces CaM phosphorylation at Tyr(99) by a Src family kinase and that phosphorylated CaM activates PI3K to produce PIP3, which promotes TRPC6 translocation to the cell membrane. PMID- 26858458 TI - Balanced feedforward inhibition and dominant recurrent inhibition in olfactory cortex. AB - Throughout the brain, the recruitment of feedforward and recurrent inhibition shapes neural responses. However, disentangling the relative contributions of these often-overlapping cortical circuits is challenging. The piriform cortex provides an ideal system to address this issue because the interneurons responsible for feedforward and recurrent inhibition are anatomically segregated in layer (L) 1 and L2/3 respectively. Here we use a combination of optical and electrical activation of interneurons to profile the inhibitory input received by three classes of principal excitatory neuron in the anterior piriform cortex. In all classes, we find that L1 interneurons provide weaker inhibition than L2/3 interneurons. Nonetheless, feedforward inhibitory strength covaries with the amount of afferent excitation received by each class of principal neuron. In contrast, intracortical stimulation of L2/3 evokes strong inhibition that dominates recurrent excitation in all classes. Finally, we find that the relative contributions of feedforward and recurrent pathways differ between principal neuron classes. Specifically, L2 neurons receive more reliable afferent drive and less overall inhibition than L3 neurons. Alternatively, L3 neurons receive substantially more intracortical inhibition. These three features--balanced afferent drive, dominant recurrent inhibition, and differential recruitment by afferent vs. intracortical circuits, dependent on cell class--suggest mechanisms for olfactory processing that may extend to other sensory cortices. PMID- 26858460 TI - Early and multiple origins of metastatic lineages within primary tumors. AB - Many aspects of the evolutionary process of tumorigenesis that are fundamental to cancer biology and targeted treatment have been challenging to reveal, such as the divergence times and genetic clonality of metastatic lineages. To address these challenges, we performed tumor phylogenetics using molecular evolutionary models, reconstructed ancestral states of somatic mutations, and inferred cancer chronograms to yield three conclusions. First, in contrast to a linear model of cancer progression, metastases can originate from divergent lineages within primary tumors. Evolved genetic changes in cancer lineages likely affect only the proclivity toward metastasis. Single genetic changes are unlikely to be necessary or sufficient for metastasis. Second, metastatic lineages can arise early in tumor development, sometimes long before diagnosis. The early genetic divergence of some metastatic lineages directs attention toward research on driver genes that are mutated early in cancer evolution. Last, the temporal order of occurrence of driver mutations can be inferred from phylogenetic analysis of cancer chronograms, guiding development of targeted therapeutics effective against primary tumors and metastases. PMID- 26858459 TI - High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates. AB - The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis. PMID- 26858462 TI - Latin American Immigration, Maternal Education, and Approaches to Managing Children's Schooling in the United States. AB - Concerted cultivation is the active parental management of children's educations that, because it differs by race/ethnicity, nativity, and socioeconomic status, plays a role in early educational disparities. Analyses of the Early Childhood Longitudinal Study-Kindergarten Cohort (n = 10,913) revealed that foreign-born Latina mothers were generally less likely to engage in school-based activities, enroll children in extracurricular activities, or provide educational materials at home when children were at the start of elementary school than were U.S.-born White, African American, and Latina mothers, in part because of their lower educational attainment. Within the foreign-born Latina sample, the link between maternal education and the three concerted cultivation behaviors did not vary by whether the education was attained in the United States or Latin America. Higher maternal education appeared to matter somewhat more to parenting when children were girls and had higher achievement. PMID- 26858463 TI - Antisymmetric tensor generalizations of affine vector fields. AB - Tensor generalizations of affine vector fields called symmetric and antisymmetric affine tensor fields are discussed as symmetry of spacetimes. We review the properties of the symmetric ones, which have been studied in earlier works, and investigate the properties of the antisymmetric ones, which are the main theme in this paper. It is shown that antisymmetric affine tensor fields are closely related to one-lower-rank antisymmetric tensor fields which are parallelly transported along geodesics. It is also shown that the number of linear independent rank-p antisymmetric affine tensor fields in n-dimensions is bounded by (n + 1)!/p!(n - p)!. We also derive the integrability conditions for antisymmetric affine tensor fields. Using the integrability conditions, we discuss the existence of antisymmetric affine tensor fields on various spacetimes. PMID- 26858461 TI - From chlorite dismutase towards HemQ - the role of the proximal H-bonding network in haeme binding. AB - Chlorite dismutase (Cld) and HemQ are structurally and phylogenetically closely related haeme enzymes differing fundamentally in their enzymatic properties. Clds are able to convert chlorite into chloride and dioxygen, whereas HemQ is proposed to be involved in the haeme b synthesis of Gram-positive bacteria. A striking difference between these protein families concerns the proximal haeme cavity architecture. The pronounced H-bonding network in Cld, which includes the proximal ligand histidine and fully conserved glutamate and lysine residues, is missing in HemQ. In order to understand the functional consequences of this clearly evident difference, specific hydrogen bonds in Cld from 'Candidatus Nitrospira defluvii' (NdCld) were disrupted by mutagenesis. The resulting variants (E210A and K141E) were analysed by a broad set of spectroscopic (UV-vis, EPR and resonance Raman), calorimetric and kinetic methods. It is demonstrated that the haeme cavity architecture in these protein families is very susceptible to modification at the proximal site. The observed consequences of such structural variations include a significant decrease in thermal stability and also affinity between haeme b and the protein, a partial collapse of the distal cavity accompanied by an increased percentage of low-spin state for the E210A variant, lowered enzymatic activity concomitant with higher susceptibility to self-inactivation. The high-spin (HS) ligand fluoride is shown to exhibit a stabilizing effect and partially restore wild-type Cld structure and function. The data are discussed with respect to known structure-function relationships of Clds and the proposed function of HemQ as a coprohaeme decarboxylase in the last step of haeme biosynthesis in Firmicutes and Actinobacteria. PMID- 26858464 TI - Biogeography of "Cyprinella lutrensis": intensive genetic sampling from the Pecos River 'melting pot' reveals a dynamic history and phylogenetic complexity. AB - Thorough sampling is necessary to delineate lineage diversity for polytypic "species" such as Cyprinella lutrensis. We conducted extensive mtDNA sampling (cytochrome b and ND4) from the Pecos River, Rio Grande, and South Canadian River, New Mexico. Our study emphasized the Pecos River due to its complex geological history and potential to harbor multiple lineages. We used geometric morphometric, morphometric, and meristic analyses to test for phenotypic divergence and combined nucDNA with mtDNA to test for cytonuclear disequilibrium and combined our sequences with published data to conduct a phylogenetic re assessment of the entire C. lutrensis clade. We detected five co-occurring mtDNA lineages in the Pecos River, but no evidence for cytonuclear disequilibrium or phenotypic divergence. Recognized species were interspersed amongst divergent lineages of "C. lutrensis". Allopatric divergence among drainages isolated in the Late Miocene and Pliocene apparently produced several recognized species and major divisions within "C. lutrensis". Pleistocene re-expansion and subsequent re fragmentation of a centralized lineage founded younger, divergent lineages throughout the Rio Grande basin and Edwards Plateau. There is also evidence of recent introductions to the Rio Grande, Pecos and South Canadian Rivers. Nonetheless, deeply divergent lineages have coexisted since the Pleistocene. PMID- 26858465 TI - Synthesis of Lobeline, Lobelane and their Analogues. A Review. PMID- 26858467 TI - The Empirical Distribution of a Large Number of Correlated Normal Variables. AB - Motivated by the advent of high dimensional highly correlated data, this work studies the limit behavior of the empirical cumulative distribution function (ecdf) of standard normal random variables under arbitrary correlation. First, we provide a necessary and sufficient condition for convergence of the ecdf to the standard normal distribution. Next, under general correlation, we show that the ecdf limit is a random, possible infinite, mixture of normal distribution functions that depends on a number of latent variables and can serve as an asymptotic approximation to the ecdf in high dimensions. We provide conditions under which the dimension of the ecdf limit, defined as the smallest number of effective latent variables, is finite. Estimates of the latent variables are provided and their consistency proved. We demonstrate these methods in a real high-dimensional data example from brain imaging where it is shown that, while the study exhibits apparently strongly significant results, they can be entirely explained by correlation, as captured by the asymptotic approximation developed here. PMID- 26858466 TI - A continuous linear optimal transport approach for pattern analysis in image datasets. AB - We present a new approach to facilitate the application of the optimal transport metric to pattern recognition on image databases. The method is based on a linearized version of the optimal transport metric, which provides a linear embedding for the images. Hence, it enables shape and appearance modeling using linear geometric analysis techniques in the embedded space. In contrast to previous work, we use Monge's formulation of the optimal transport problem, which allows for reasonably fast computation of the linearized optimal transport embedding for large images. We demonstrate the application of the method to recover and visualize meaningful variations in a supervised-learning setting on several image datasets, including chromatin distribution in the nuclei of cells, galaxy morphologies, facial expressions, and bird species identification. We show that the new approach allows for high-resolution construction of modes of variations and discrimination and can enhance classification accuracy in a variety of image discrimination problems. PMID- 26858468 TI - Nonparametric restricted mean analysis across multiple follow-up intervals. AB - We provide a nonparametric estimate of tau-restricted mean survival using follow up information beyond tauwhen appropriate to improve precision. The variance accounts for correlation between follow-up windows. Both asymptotic calculations and simulation studies recommend follow-up intervals spaced approximately tau/2 apart. PMID- 26858469 TI - The Applied Mindfulness Process Scale (AMPS): A process measure for evaluating mindfulness-based interventions. AB - OBJECTIVE: Mindfulness-based interventions (MBIs) include the application of meditation and mind-body practices used to promote mindful awareness in daily life. Operationalizing the construct of mindfulness is important in order to determine mechanisms of therapeutic change elicited by mindfulness practice. In addition to existing state and trait measures of mindfulness, process measures are needed to assess the ways in which individuals apply mindfulness in the context of their practice. METHOD: This report details three independent studies (qualitative interview, N = 8; scale validation, N = 134; and replication study, N = 180) and the mixed qualitative-quantitative methodology used to develop and validate the Applied Mindfulness Process Scale (AMPS), a 15-item process measure designed to quantify how mindfulness practitioners actively use mindfulness to remediate psychological suffering in their daily lives. RESULTS: In Study 1, cognitive interviewing yielded a readily comprehensible and accessible scale of 15 items. In Study 2, exploratory factor analysis derived a potential three factor solution: decentering, positive emotion regulation, and negative emotion regulation. In Study 3, confirmatory factor analysis verified better model fit with the three-factor structure over the one-factor structure. CONCLUSIONS: AMPS functions as a measure to quantify the application of mindfulness and processes of change in the context of MBIs and general mindfulness practice. PMID- 26858470 TI - Computerized Writing and Reading Instruction for Students in Grades 4 to 9 With Specific Learning Disabilities Affecting Written Language. AB - Computer scientists and educational researchers evaluated effectiveness of computerized instruction tailored to evidence-based impairments in specific learning disabilities (SLDs) in students in grades 4 to 9 with persisting SLDs despite prior extra help. Following comprehensive, evidence-based differential diagnosis for dysgraphia (impaired handwriting), dyslexia (impaired word reading and spelling), and oral and written language learning disability (OWL LD), students completed 18 sessions of computerized instruction over about 3 months. The 11 students taught letter formation with sequential, numbered, colored arrow cues with full contours who wrote letters on lines added to iPAD screen showed more and stronger treatment effects than the 21 students taught using only visual motion cues for letter formation who wrote on an unlined computer monitor. Teaching to all levels of language in multiple functional language systems (by ear, eye, mouth, and hand) close in time resulted in significant gains in reading and writing skills for the group and in diagnosed SLD hallmark impairments for individuals; also, performance on computerized learning activities correlated with treatment gains. Results are discussed in reference to need for both accommodations and explicit instruction for persisting SLDs and the potential for computers to teach handwriting, morphophonemic orthographies, comprehension, and composition. PMID- 26858471 TI - Intramolecular Hydrogen Transfer Reactions Catalyzed by Pentamethylcyclopentadienyl Rhodium and Cobalt Olefin Complexes: Mechanistic Studies. AB - The mechanism of intramolecular transfer dehydrogenation catalyzed by [Cp*M(VTMS)2] (1, M=Rh, 2, M=Co, Cp* = C5Me5, VTMS = vinyltrimethylsilane) complexes has been studied using vinyl silane protected alcohols as substrates. Deuterium-labeled substrates have been synthesized and the regioselectivity of H/D transfers investigated using 1H and 2H NMR spectroscopy. The labeling studies establish a regioselective pathway consisting of alkene directed alpha C-H activation, 2,1 alkene insertion, and finally beta-hydride elimination to give silyl enol ether products. PMID- 26858472 TI - Contact Line Instability of Gravity-Driven Flow of Power-Law Fluids. AB - The moving contact line of a thin fluid film can often corrugate into fingers, which is also known as a fingering instability. Although the fingering instability of Newtonian fluids has been studied extensively, there are few studies published on contact line fingering instability of non-Newtonian fluids. In particular, it is still unknown how shear-thinning rheological properties can affect the formation, growth, and shape of a contact line instability. Our previous study (Hu and Kieweg, 2012) showed a decreased capillary ridge formation for more shear-thinning fluids in a 2D model (i.e. 1D thin film spreading within the scope of lubrication theory). Those results motivated this study's hypothesis: more shear-thinning fluids should have suppressed finger growth and longer finger wavelength, and this should be evident in linear stability analysis (LSA) and 3D (i.e. 2D spreading) numerical simulations. In this study, we developed a LSA model for the gravity-driven flow of shear-thinning films, and carried out a parametric study to investigate the impact of shear-thinning on the growth rate of the emerging fingering pattern. A fully 3D model was also developed to compare and verify the LSA results using single perturbations, and to explore the result of multiple-mode, randomly imposed perturbations. Both the LSA and 3D numerical results confirmed that the contact line fingers grow faster for Newtonian fluids than the shear-thinning fluids on both vertical and inclined planes. In addition, both the LSA and 3D model indicated that the Newtonian fluids form fingers with shorter wavelengths than the shear-thinning fluids when the plane is inclined; no difference in the most unstable (i.e. emerging) wavelength was observed at vertical. This study also showed that the distance between emerging fingers was smaller on a vertical plane than on a less-inclined plane for shear-thinning fluids, as previously shown for Newtonian fluids. For the first time for shear-thinning fluids, these results connect trends in capillary ridge and contact line finger formation in 2D models, LSA, and 3D simulations. The results can provide us insights on how to optimize non-Newtonian fluid properties to minimize a fingering instability in many industrial and biological applications. PMID- 26858473 TI - A clinico radiographic study of immediate loading implants in rehabilitation of mandibular ridges. AB - BACKGROUND: Numerous studies regarding the immediate loading of splinted implants retaining/supporting mandibular dentures have reported promising results, but studies comparing splinted and unsplinted attachments for supporting overdentures with immediate loading are limited. Scientific literature is sparse comparing various attachment systems and patient satisfaction in response to immediately loaded implant supported overdentures. METHODS: A total of 30 completely edentulous patients male or female, in the age group of 54-78 years (mean age 65 years), wearing conventional complete dentures were selected and randomly divided in to two groups. A total of 60 implants were placed in the interforaminal area of the mental symphysis (two implants per patients) in 30 patients. Two types of attachment systems namely Ball for group-A and Bar for group-B were used and immediate loading done. Implants were evaluated clinically and radiographically at baseline, 1 month, 3 months, 6 months and 9 months. All clinical and radiographic parameters were subjected to statistical analysis. RESULT: The implant survival rate for group-A (ball attachment) was 93.3% and implant survival rate for group-B (bar attachment) was 93.3%. The overall implant survival rate was not dependent on the attachment system. There was no significant difference in the crestal bone loss in mesial, and distal side in implants with respect to ball and bar attachment for different period of observation (F = 0.25; P = 0.910; F = 0.07; P = 0.992 respectively). CONCLUSION: Overdenture supported by two implants should be the minimum gold standard in the rehabilitation of completely edentulous patients. PMID- 26858474 TI - The dental specialties related articles published in Medical Journal Armed Forces India from 2000 to 2014 over a 15-year period. AB - There is a paucity of information about the dental specialties related articles published in the Medical Journal Armed Forces India (MJAFI). This study aimed to audit the dental specialities related articles published in MJAFI from 2000 to 2014 over a 15-year period. Bibliometric analysis of sixty issues of MJAFI from 2000 to 2014 were performed using web-based search. The articles published were analyzed for type of article and topic of individual dental specialities. The articles published were also evaluated to identify whether the study was an Armed Forces Medical Research Committee Project or funded research project or not. Out of the total 118 published articles related to dental specialities, original articles (55) and case reports (49) contribute the major share. The highest number of dental specialities related articles was published in 2009 with 16, followed by 2010 with 13 and 2011 with 11 and the least published year was 2013 with 3 articles. Regarding the relationship with dental specialities, the maximum number of published articles were related to oral medicine and radiology (56) followed by oral and maxillofacial surgery (49), orthodontics (23) and prosthodontics (17). Among the articles published in MJAFI, maxillofacial injuries (11) followed by orthodontic treatment (8) and craniofacial deformities (8) form the major attraction of the contributors. Among the 118 dental speciality articles, there were only 4 Armed Forces Medical Research Committee Project articles and 19 funded research project articles. An equal distribution of articles related to clinical dentistry and nonclinical dentistry is maintained for the MJAFI from 2000 to 2014 over a 15-year period. PMID- 26858475 TI - Post-traumatic 'transection' of the aorta. PMID- 26858476 TI - Mesenteric cyst in sigmoid mesocolon - A rare location and its laparoscopic excision. PMID- 26858477 TI - Sporotrichum pruniosum causing a rare invasive infection in an immunocompromised patient. PMID- 26858478 TI - Aesthetic management of a discoloured non-vital immature maxillary central incisor. PMID- 26858479 TI - A simplified approach for prosthodontic management of syndromic oligodontia. PMID- 26858480 TI - Total shoulder girdle reconstruction after resection of malignant tumor of scapula. PMID- 26858481 TI - Presence of atypical antibody (anti Jk(a)) in a multi transfused transfusion dependent anemia patient. PMID- 26858482 TI - A case of idiopathic choroidal neovascular membrane in a young patient. PMID- 26858483 TI - A case of hoarseness of voice. PMID- 26858484 TI - Management of middle mesial canal under dental operating microscope. PMID- 26858485 TI - Accessory belly of digastric muscle presenting as a submandibular space mass. PMID- 26858487 TI - Management of a case of velopharyngeal insufficiency with multidisciplinary approach. PMID- 26858486 TI - Unusual coexistence of bilateral optic disc pits with unilateral macular hole. PMID- 26858488 TI - Perseverance pays: A complicated case of post laparoscopic cholecystectomy duodenal injury. PMID- 26858489 TI - Vascularised fibula osteocutaneous flap for mandibular reconstruction and multiple implant retained fixed prosthetic rehabilitation of a patient with mandibular ameloblastoma. PMID- 26858490 TI - Two cases of Acute Lung Injury following closed space smoke inhalation. PMID- 26858491 TI - Endodontic management of small molars. PMID- 26858492 TI - Specially designed tooth supported mandibular overdenture with enhanced retention. PMID- 26858493 TI - Nystagmus surgery: Our experience. PMID- 26858494 TI - Comprehensive rehabilitation of a case of Amelogenesis imperfecta. PMID- 26858495 TI - Prosthodontic rehabilitation of extraoral and intraoral maxillofacial defects. PMID- 26858496 TI - Acute onset myopia - A rare presentation of systemic lupus erythematosus. PMID- 26858497 TI - Hepatic cystic mesenchymal hamartoma. PMID- 26858498 TI - Telescopic retainers for removable partial dentures. PMID- 26858499 TI - Nasopharyngeal tuberculosis. PMID- 26858500 TI - Maxillary first molar with a single canal in a patient with bilateral cleft lip and palate repair. PMID- 26858501 TI - Disseminated histoplasmosis presenting as a case of erythema nodosum and hemophagocytic lymphohistiocytosis. PMID- 26858502 TI - A simple antirotational mechanism in a posterior two piece post and core. PMID- 26858503 TI - Prosthetic rehabilitation of a gunshot wound defect with combination of fixed and removable prosthesis. PMID- 26858504 TI - New Delhi metallo-beta-lactamase producing extensively drug-resistant Raoultella ornithinolytica isolated from drain fluid following Whipple's pancreaticoduodenectomy. PMID- 26858505 TI - Management of a maxillary first molar with morphological aberration using spiral computed tomography. PMID- 26858506 TI - Isolated unilateral oculomotor nerve palsy following a mild head injury. PMID- 26858507 TI - Consistent Model Selection in Segmented Line Regression. AB - The Schwarz criterion or Bayes Information Criterion (BIC) is often used to select a model dimension, and some variations of the BIC have been proposed in the context of change-point problems. In this paper, we consider a segmented line regression model with an unknown number of change-points and study asymptotic properties of Schwarz type criteria in selecting the number of change-points. Noticing the overestimating tendency of the traditional BIC observed in some empirical studies and being motivated by asymptotic behavior of the modified BIC proposed by Zhang and Siegmund (2007), we consider a variation of the Schwarz type criterion that applies a harsher penalty equivalent to the model with one additional unknown parameter per segment. For the segmented line regression model without the continuity constraint, we prove the consistency of the number of change-points selected by the criterion with such type of a modification and summarize the simulation results that support the consistency. Further simulations are conducted for the model with the continuity constraint, and we empirically observe that the asymptotic behavior of this modified version of BIC is comparable to that of the criterion proposed by Liu, Wu, and Zidek (1997). PMID- 26858508 TI - Multiple Imputation for Missing Edge Data: A Predictive Evaluation Method with Application to Add Health. AB - Recent developments have made model-based imputation of network data feasible in principle, but the extant literature provides few practical examples of its use. In this paper we consider 14 schools from the widely used In-School Survey of Add Health (Harris et al., 2009), applying an ERGM-based estimation and simulation approach to impute the network missing data for each school. Add Health's complex study design leads to multiple types of missingness, and we introduce practical techniques for handing each. We also develop a cross-validation based method - Held-Out Predictive Evaluation (HOPE) - for assessing this approach. Our results suggest that ERGM-based imputation of edge variables is a viable approach to the analysis of complex studies such as Add Health, provided that care is used in understanding and accounting for the study design. PMID- 26858509 TI - Reply to comment on "Serving Transgender Youth: Challenges, Dilemmas, and Clinical Examples" by Tishelman et al. (2015). PMID- 26858510 TI - Observational Word Learning: Beyond Propose-But-Verify and Associative Bean Counting. AB - Learning new words is difficult. In any naming situation, there are multiple possible interpretations of a novel word. Recent approaches suggest that learners may solve this problem by tracking co-occurrence statistics between words and referents across multiple naming situations (e.g. Yu & Smith, 2007), overcoming the ambiguity in any one situation. Yet, there remains debate around the underlying mechanisms. We conducted two experiments in which learners acquired eight word-object mappings using cross-situational statistics while eye-movements were tracked. These addressed four unresolved questions regarding the learning mechanism. First, eye-movements during learning showed evidence that listeners maintain multiple hypotheses for a given word and bring them all to bear in the moment of naming. Second, trial-by-trial analyses of accuracy suggested that listeners accumulate continuous statistics about word/object mappings, over and above prior hypotheses they have about a word. Third, consistent, probabilistic context can impede learning, as false associations between words and highly co occurring referents are formed. Finally, a number of factors not previously considered in prior analysis impact observational word learning: knowledge of the foils, spatial consistency of the target object, and the number of trials between presentations of the same word. This evidence suggests that observational word learning may derive from a combination of gradual statistical or associative learning mechanisms and more rapid real-time processes such as competition, mutual exclusivity and even inference or hypothesis testing. PMID- 26858511 TI - Talker-specificity and adaptation in quantifier interpretation. AB - Linguistic meaning has long been recognized to be highly context-dependent. Quantifiers like many and some provide a particularly clear example of context dependence. For example, the interpretation of quantifiers requires listeners to determine the relevant domain and scale. We focus on another type of context dependence that quantifiers share with other lexical items: talker variability. Different talkers might use quantifiers with different interpretations in mind. We used a web-based crowdsourcing paradigm to study participants' expectations about the use of many and some based on recent exposure. We first established that the mapping of some and many onto quantities (candies in a bowl) is variable both within and between participants. We then examined whether and how listeners' expectations about quantifier use adapts with exposure to talkers who use quantifiers in different ways. The results demonstrate that listeners can adapt to talker-specific biases in both how often and with what intended meaning many and some are used. PMID- 26858512 TI - The general critical analysis for continuous-time UPPAM recurrent neural networks. AB - The uniformly pseudo-projection-anti-monotone (UPPAM) neural network model, which can be considered as the unified continuous-time neural networks (CNNs), includes almost all of the known CNNs individuals. Recently, studies on the critical dynamics behaviors of CNNs have drawn special attentions due to its importance in both theory and applications. In this paper, we will present the analysis of the UPPAM network under the general critical conditions. It is shown that the UPPAM network possesses the global convergence and asymptotical stability under the general critical conditions if the network satisfies one quasi-symmetric requirement on the connective matrices, which is easy to be verified and applied. The general critical dynamics have rarely been studied before, and this work is an attempt to gain an meaningful assurance of general critical convergence and stability of CNNs. Since UPPAM network is the unified model for CNNs, the results obtained here can generalize and extend the existing critical conclusions for CNNs individuals, let alone those non-critical cases. Moreover, the easily verified conditions for general critical convergence and stability can further promote the applications of CNNs. PMID- 26858514 TI - Accidents and Apathy: The Construction of the 'Robens Philosophy' of Occupational Safety and Health Regulation in Britain, 1961-1974. AB - The 1972 Robens Report is widely regarded to have provided the underlying rationale for the 'modern' system of occupational health and safety regulation in Britain, embodied in the Health and Safety at Work Act (HSW Act) 1974. The HSW Act advanced a new, more flexible system of regulation, premised on the ideal of self-regulation by industry. This article advances a more nuanced historical understanding of the Report and its ethos-the 'Robens philosophy'-than hitherto developed, situating its assumptions about accidents, regulation and the role of the state in the social, economic and political context of Britain in the 1960s and early 1970s. Highlighting the interaction between these trends and long established regulatory practices, the article argues that the turn to 'self regulation' heralded by the Robens Report was highly convincing from a political and regulatory perspective at the time it was promulgated. PMID- 26858513 TI - Synthesis of CuNP-Modified Carbon Electrodes Obtained by Pyrolysis of Paper. AB - A one-step approach for the synthesis and integration of copper nanoparticles (CuNPs) onto paper-based carbon electrodes is herein reported. The method is based on the pyrolysis (1000 degrees C under a mixture of 95% Ar / 5% H2 for 1 hour) of paper strips modified with a saturated solution of CuSO4 and yields to the formation of abundant CuNPs on the surface of carbonized cellulose fibers. The resulting substrates were characterized by a combination of scanning electron microscopy, EDX, Raman spectroscopy as well as electrical and electrochemical techniques. Their potential application, as working electrodes for nonenzymatic amperometric determination of glucose, was then demonstrated (linear response up to 3 mM and a sensitivity of 460 +/- 8 MUA.cm-2.mM-1). Besides being a simple and inexpensive process for the development of electrochemically-active substrates, this approach opens new possibilities for the in-situ synthesis of metallic nanoparticles without the traditional requirements of solutions and adjuvants. PMID- 26858515 TI - British Romantic Generalism in the Age of Specialism, 1870-1990. AB - This essay explores the impact of 'generalism' and 'general practice' on the specialisation of British medicine using the case of neurology in Britain to reveal characteristics of British 'generalist medical culture' from 1870 to 1990. It argues that 'generalism' represented a particular epistemological position in Victorian medicine, one that then created a natural bridge between science and medicine over which almost all physicians and scientists were comfortable walking. The legacies of that Victorian 'generalist preference' exerted an enduring impact on the specialisation process as physicians experienced it in the twentieth century and as this case of neurology reveals so clearly. Neurologists and general physicians would still be arguing about the relative merits of a general medical education into the 1980s. By then, however, the emergence of government bodies promoting specialist labour conditions would have rendered the process seemingly inexorable. PMID- 26858517 TI - Moving Psychopathology Forward. PMID- 26858516 TI - Involvement of Angiopoietin-2 and Tie2 Receptor Phosphorylation in STEC-HUS Mediated by Escherichia coli O104:H4. AB - Escherichia coli O104:H4-associated hemolytic uremic syndrome (HUS) is characterized by Shiga toxin-induced vascular damage. As indicated by recent studies, dysregulation of the angiopoietin (Angpt)/Tie2 ligand receptor system may be crucial for endothelial dysfunction in HUS. Early Angpt-2 levels quantified in 48 adult HUS patients were predictive for a complicated clinical course, in particular for need of hemodialysis and mechanical ventilation as well as occurrence of seizures. In vitro challenge of human umbilical vein endothelial cells with patients' sera indicated an injurious mediator role of Angpt-2 opening future perspectives for mitigating endothelial activation in HUS. PMID- 26858518 TI - Gene regulation network inference with joint sparse Gaussian graphical models. AB - Revealing biological networks is one key objective in systems biology. With microarrays, researchers now routinely measure expression profiles at the genome level under various conditions, and, such data may be utilized to statistically infer gene regulation networks. Gaussian graphical models (GGMs) have proven useful for this purpose by modeling the Markovian dependence among genes. However, a single GGM may not be adequate to describe the potentially differing networks across various conditions, and hence it is more natural to infer multiple GGMs from such data. In the present study, we propose a class of nonconvex penalty functions aiming at the estimation of multiple GGMs with a flexible joint sparsity constraint. We illustrate the property of our proposed nonconvex penalty functions by simulation study. We then apply the method to a gene expression data set from the GenCord Project, and show that our method can identify prominent pathways across different conditions. PMID- 26858519 TI - Effects of socio-demographic factors on parental monitoring, and regimen adherence among adolescents with type 1 diabetes: A moderation analysis. AB - Parental monitoring of adolescent diabetes care is an important predictor of adolescent regimen adherence. To date, no studies have investigated whether socio demographic factors are associated with low levels of parental monitoring or differences in parental monitoring styles, and their moderating effects in families of adolescents with type 1 diabetes. The purpose of this cross-sectional study was to determine whether youth and family socio-demographic factors moderated the relationship between monitoring and youth regimen adherence (i.e., mean frequency of blood glucose testing [BGT]). Data were collected from 267 adolescents with type 1 diabetes and their parents. Hierarchical multiple regression analyses were employed. Socio-demographic factors accounted for 17.1% of the variance in adherence. After parental monitoring scales were entered, R2 in all eight equations increased and R2 change score in six of eight equations were significant. All models were significant after the interaction terms were entered. In the adolescent report models, parent age and family structure were both independently associated with adherence and also moderated the association between adolescent-report parental monitoring and adherence to diabetes care, in particular, adolescent report of parental direct observation/presence during diabetes care. In the parent report models, income was moderated the association between parent-report youth disclosure and adherence. Research should focus on identifying additional modifiable factors that place families at risk for low levels of parental monitoring of diabetes care. Future clinical research is needed to help identify risk factors for low levels of parental monitoring and develop interventions to promote optimal parenting skills that can support youth diabetes care. PMID- 26858520 TI - An immersed boundary method for two-phase fluids and gels and the swimming of Caenorhabditis elegans through viscoelastic fluids. AB - The swimming of microorganisms typically involves the undulation or rotation of thin, filamentary objects in a fluid or other medium. Swimming in Newtonian fluids has been examined extensively, and only recently have investigations into microorganism swimming through non-Newtonian fluids and gels been explored. The equations that govern these more complex media are often nonlinear and require computational algorithms to study moderate to large amplitude motions of the swimmer. Here, we develop an immersed boundary method for handling fluid structure interactions in a general two-phase medium, where one phase is a Newtonian fluid and the other phase is viscoelastic (e.g., a polymer melt or network). We use this algorithm to investigate the swimming of an undulating, filamentary swimmer in 2D (i.e., a sheet). A novel aspect of our method is that it allows one to specify how forces produced by the swimmer are distributed between the two phases of the fluid. The algorithm is validated by comparing theoretical predictions for small amplitude swimming in gels and viscoelastic fluids. We show how the swimming velocity depends on material parameters of the fluid and the interaction between the fluid and swimmer. In addition, we simulate the swimming of Caenorhabditis elegans in viscoelastic fluids and find good agreement between the swimming speeds and fluid flows in our simulations and previous experimental measurements. These results suggest that our methodology provides an accurate means for exploring the physics of swimming through non Newtonian fluids and gels. PMID- 26858521 TI - Facial averageness and genetic quality: Testing heritability, genetic correlation with attractiveness, and the paternal age effect. AB - Popular theory suggests that facial averageness is preferred in a partner for genetic benefits to offspring. However, whether facial averageness is associated with genetic quality is yet to be established. Here, we computed an objective measure of facial averageness for a large sample (N = 1,823) of identical and nonidentical twins and their siblings to test two predictions from the theory that facial averageness reflects genetic quality. First, we use biometrical modelling to estimate the heritability of facial averageness, which is necessary if it reflects genetic quality. We also test for a genetic association between facial averageness and facial attractiveness. Second, we assess whether paternal age at conception (a proxy of mutation load) is associated with facial averageness and facial attractiveness. Our findings are mixed with respect to our hypotheses. While we found that facial averageness does have a genetic component, and a significant phenotypic correlation exists between facial averageness and attractiveness, we did not find a genetic correlation between facial averageness and attractiveness (therefore, we cannot say that the genes that affect facial averageness also affect facial attractiveness) and paternal age at conception was not negatively associated with facial averageness. These findings support some of the previously untested assumptions of the 'genetic benefits' account of facial averageness, but cast doubt on others. PMID- 26858522 TI - Comparison of microbiology and visual outcomes of patients undergoing small-gauge and 20-gauge vitrectomy for endophthalmitis. AB - BACKGROUND: The role of pars plana vitrectomy (PPV) for endophthalmitis has evolved over recent decades but the literature is lacking on comparisons between small-gauge and 20-gauge vitrectomy. OBJECTIVE: To evaluate evolving etiological and microbiological trends in patients undergoing vitrectomy for endophthalmitis and to compare culture-positive rates and visual outcomes between small-gauge (23 and 25-gauge) and 20-gauge instrumentation during vitrectomy for endophthalmitis. METHODS: Ten-year retrospective comparative case series and prospective laboratory in vitro testing. Tertiary care academic referral center. Patients who underwent PPV for endophthalmitis between 2003 and 2013. Vitreous biopsies were obtained in all cases. The effect of vitrectomy gauge (20-, 23-, and 25-gauge) and vitreous cutting rate (1,500 and 5,000 cuts per minute) on the viability of bacterial culture was evaluated in an in vitro prospective laboratory investigation. MAIN OUTCOME MEASURES: Comparison of etiology, microbiology culture-positive rates, and visual outcomes between small-gauge and 20-gauge instrumentation in patients undergoing PPV for infectious endophthalmitis. RESULTS: A total of 61 cases of vitrectomy for endophthalmitis were identified over a 10-year period; of these, 34 were treated with small-gauge (23- and 25-gauge) vitrectomy and 27 were treated with 20-gauge vitrectomy. In the small-gauge group, 12 cases (35.3%) yielded culture-positive results versus 20 cases (74.1%) with culture positivity in the 20-gauge cohort (P=0.002). The most common cause of endophthalmitis was cataract surgery and the most frequently identified organism was coagulase-negative Staphylococci in both groups. There was no significant difference in mean postoperative visual acuities between groups (P=0.33). Etiological trends indicate an increase in endophthalmitis due to intravitreal injection in the small-gauge group (n=9) compared to the 20-gauge group (n=3) (P=0.001). In vitro laboratory testing revealed no significant difference in rates of culture growth for different vitrectomy gauge sizes or vitreous cutting speeds. CONCLUSION AND RELEVANCE: Small-gauge vitrectomy for endophthalmitis yields final visual outcomes comparable to 20-gauge instrumentation. A significant difference in culture-positive rates was observed between small-gauge and 20-gauge instrumentation for vitrectomy in endophthalmitis; however, laboratory testing indicates this is not related to either vitreous gauge size or cutter speed. Intravitreal injections are emerging as a common etiology of vitrectomy for endophthalmitis. PMID- 26858523 TI - Lipegfilgrastim in the management of chemotherapy-induced neutropenia of cancer patients. AB - Neutropenia and febrile neutropenia (FN) are frequent and potentially fatal toxicities of myelosuppressive anticancer treatments. The introduction of granulocyte colony-stimulating factors (G-CSFs) in clinical practice has remarkably reduced the duration and severity of neutropenia, as well as the incidence of FN, thus allowing the administration of chemotherapeutic agents at the optimal dose and time with lower risk. The current scenario of G-CSFs in Europe includes filgrastim, lenograstim, some G-CSF biosimilars, and pegfilgrastim. Recently, a novel long-acting G-CSF, lipegfilgrastim, became available. Lipegfilgrastim is a glycopegylated G-CSF, alternative to pegfilgrastim, and has shown in randomized trials, to be equivalent to pegfilgrastim in reducing the incidence of severe neutropenia and FN in patients with breast cancer receiving chemotherapy, with a similar safety profile. Furthermore, lipegfilgrastim was more effective than the placebo in reducing the incidence of severe neutropenia, its duration, and time to absolute neutrophil count recovery, in patients with non-small cell lung cancer receiving myelosuppressive therapy. Although the number of studies currently published is still limited, lipegfilgrastim seems to be a promising drug in the management of chemotherapy-induced neutropenia. PMID- 26858524 TI - Folic acid targeted Mn:ZnS quantum dots for theranostic applications of cancer cell imaging and therapy. AB - In this study, we synthesized a multifunctional nanoparticulate system with specific targeting, imaging, and drug delivering functionalities by following a three-step protocol that operates at room temperature and solely in aqueous media. The synthesis involves the encapsulation of luminescent Mn:ZnS quantum dots (QDs) with chitosan not only as a stabilizer in biological environment, but also to further provide active binding sites for the conjugation of other biomolecules. Folic acid was incorporated as targeting agent for the specific targeting of the nanocarrier toward the cells overexpressing folate receptors. Thus, the formed composite emits orange-red fluorescence around 600 nm and investigated to the highest intensity at Mn(2+) doping concentration of 15 at.% and relatively more stable at low acidic and low alkaline pH levels. The structural characteristics and optical properties were thoroughly analyzed by using Fourier transform infrared, X-ray diffraction, dynamic light scattering, ultraviolet-visible, and fluorescence spectroscopy. Further characterization was conducted using thermogravimetric analysis, high-resolution transmission electron microscopy, field emission scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray fluorescence, and X-ray photoelectron spectroscopy. The cell viability and proliferation studies by means of MTT assay have demonstrated that the as-synthesized composites do not exhibit any toxicity toward the human breast cell line MCF-10 (noncancer) and the breast cancer cell lines (MCF-7 and MDA-MB 231) up to a 500 ug/mL concentration. The cellular uptake of the nanocomposites was assayed by confocal laser scanning microscope by taking advantage of the conjugated Mn:ZnS QDs as fluorescence makers. The result showed that the functionalization of the chitosan-encapsulated QDs with folic acid enhanced the internalization and binding affinity of the nanocarrier toward folate receptor overexpressed cells. Therefore, we hypothesized that due to the nontoxic nature of the composite, the as-synthesized nanoparticulate system can be used as a promising candidate for theranostic applications, especially for a simultaneous targeted drug delivery and cellular imaging. PMID- 26858525 TI - Risk factors associated with postoperative pain after ophthalmic surgery: a prospective study. AB - BACKGROUND: Risk factors associated with postoperative pain intensity and duration, as well as consumption of analgesics after ophthalmic surgery are poorly understood. METHODS: A prospective study was conducted among adults (N=226) who underwent eye surgery at the University Hospital Split, Croatia. A day before the surgery, the patients filled out questionnaires assessing personality, anxiety, pain catastrophizing, sociodemographics and were given details about the procedure, anesthesia, and analgesia for each postoperative day. All scales were previously used for the Croatian population. The intensity of pain was measured using a numerical rating scale from 0 to 10, where 0 was no pain and 10 was the worst imaginable pain. The intensity of pain was measured before the surgery and then 1 hour, 3 hours, 6 hours, and 24 hours after surgery, and then once a day until discharge from the hospital. Univariate and multivariate analyses were performed. RESULTS: A multivariate analysis indicated that independent predictors of average pain intensity after the surgery were: absence of premedication before surgery, surgery in general anesthesia, higher pain intensity before surgery and pain catastrophizing level. Independent predictors of postoperative pain duration were intensity of pain before surgery, type of anesthesia, and self-assessment of health. Independent predictors of pain intensity >=5 during the first 6 hours after the procedure were the type of procedure, self-assessment of health, premedication, and the level of pain catastrophizing. CONCLUSION: Awareness about independent predictors associated with average postoperative pain intensity, postoperative pain duration, and occurrence of intensive pain after surgery may help health workers to improve postoperative pain management in ophthalmic surgery. PMID- 26858526 TI - Galectin-3 may serve as a potential marker for diagnosis and prognosis in papillary thyroid carcinoma: a meta-analysis. AB - BACKGROUND: Galectin-3 is a member of the beta-galactoside-binding protein family and functions as a modulator of cell growth through galactoside-binding protein correlated with the occurrence and metastasis of papillary thyroid carcinoma (PTC). METHODS: A systematic review of published articles on Web of Science and PubMed was performed. After establishing inclusion and exclusion criteria, nine articles were selected. Three studies referred to galectin-3 expression in PTC and non-PTC patients. Three studies referred to galectin-3 expression in PTC patients with lymph node metastasis (LNM) and without LNM. Three studies referred to galectin-3 expression in both PTC (with and without LNM) and non-PTC patients. Data analysis was performed by using RevMan5.2 software. RESULTS: A total of 424 patients from six eligible studies that provided data about galectin-3 expression in PTC and non-PTC patients were included. A total of 378 patients from six eligible studies that provided data about galectin-3 expression in PTC with LNM and without LNM were included. Immunohistochemistry technique was used in all the studies. Galectin-3 was found to be a highly sensitive (275/424, 64.86%) marker in the diagnosis of PTC, but was found to be expressed only in a few cases involving other types of thyroid lesions (58/424, 13.68%). The odds ratio, expressed as PTC group versus other thyroid lesions group, was 13.97 (95% CI: 7.51-26.01, P<0.00001). The results also showed that the positive expression rates of galectin-3 in PTC patients with LNM were higher than those in PTC patients without LNM. CONCLUSION: This meta-analysis demonstrated that galectin-3 may become a potentially useful immunomarker to distinguish between PTC and non PTC patients. In addition, PTC patients with positive expression of galectin-3 were more prone to LNM. PMID- 26858527 TI - Monitoring of high-density lipoprotein cholesterol level is predictive of EGFR mutation and efficacy of EGFR-TKI in patients with advanced lung adenocarcinoma. AB - High-density lipoprotein cholesterol (HDL-C) has an inverse association with the incidence of lung cancer. However, whether it can be used as a predictive factor in advanced lung adenocarcinoma patients treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) still remains undefined. This research aimed at studying the relationship of serum HDL-C baseline level and HDL C kinetics to EGFR mutation, the efficacy of EGFR-TKI, and the predictive value of PFS. The presence of mutation rate in the 192 patients with lung adenocarcinoma was compared within stratified groups. Levels of baseline HDL-C and kinetics of HDL-C were analyzed retrospectively in patients treated with EGFR TKI harboring EGFR mutation. Univariate and multivariate analyses were performed to investigate the prognostic value of HDL-C. EGFR mutation rate of HDL-C high level group was significantly higher than that of low-level group (59.0% vs 35.6%, P=0.001). Multivariate logistic analysis showed that high-level HDL-C was an independent predictive factor for EGFR gene mutation (P=0.005; odds ratio =0.417; 95% confidence interval [CI], 0.227-0.768). Patients with a low level of HDL-C before therapy showed a progression of disease in most cases (P<0.001). According to HDL-C kinetics, patients who received EGFR-TKI treatment harboring EGFR mutation were divided into four groups. Univariate analysis showed that patients in nondecreased group had longer progression-free survival (P<0.001; hazard ratio =0.003; 95% CI, 0.001-0.018). Multivariate Cox proportional hazards model analyses showed the same result (P<0.001; hazard ratio =0.003; 95% CI, 0.001-0.018). Current results suggest that HDL-C seems to be a good independent predictive biomarker for advanced lung adenocarcinoma patients treated with the first-line EGFR-TKI. Roles of this biomarker include indicating EGFR mutation, assessing the efficacy of EGFR-TKI, and predicting the progression-free survival. PMID- 26858528 TI - Utility of blood procalcitonin concentration in the management of cancer patients with infections. AB - Diagnosis of infections in cancer patients is usually problematic since differentiating between infection and fever of unknown origin is often a considerable clinical challenge. In general, increase concentration of blood procalcitonin (PCT) is associated with severe bacterial infection. PCT with an optimal cutoff level of 0.5 ng/mL seems to be the most helpful biochemical parameter in detecting severe infections, mainly bloodstream infection, in patients with hematological cancers. In all clinical situations, the elevated level of PCT should be carefully analyzed, always with a thorough physical examination and an appropriate microbiological assessment. PMID- 26858529 TI - Is kidney function affecting the management of myocardial infarction? A retrospective cohort study in patients with normal kidney function, chronic kidney disease stage III-V, and ESRD. AB - Patients with chronic kidney disease (CKD) are three times more likely to have myocardial infarction (MI) and suffer from increased morbidity and higher mortality. Traditional and unique risk factors are prevalent and constitute challenges for the standard of care. However, CKD patients have been largely excluded from clinical trials and little evidence is available to guide evidence based treatment of coronary artery disease in patients with CKD. Our objective was to assess whether a difference exists in the management of MI (ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction) among patients with normal kidney function, CKD stage III-V, and end stage renal disease (ESRD) patients. We conducted a retrospective cohort study on patients admitted to Staten Island University Hospital for the diagnosis of MI between January 2005 and December 2012. Patients were assigned to one of three groups according to their kidney function: Data collected on the medical management and the use of statins, platelet inhibitors, beta-blockers, and angiotensin converting enzyme inhibitors/angiotensin receptor blockers were compared among the three cohorts, as well as medical interventions including: catheterization and coronary artery bypass graft (CABG) when indicated. Chi square test was used to compare the proportions between nominal variables. Binary logistic analysis was used in order to determine associations between treatment modalities and comorbidities, and to account for possible confounding factors. Three hundred and thirty-four patients (mean age 67.2+/-13.9 years) were included. In terms of management, medical treatment was not different among the three groups. However, cardiac catheterization was performed less in ESRD when compared with no CKD and CKD stage III-V (45.6% vs 74% and 93.9%) (P<0.001). CABG was performed in comparable proportions in the three groups and CABG was not associated with the degree of CKD (P=0.078) in binary logistics regression. Cardiac catheterization on the other hand carried the strongest association among all studied variables (P<0.001). This association was maintained after adjusting for other comorbidities. The length of stay for the three cohorts (non-CKD, CKD stage III-V, and ESRD on hemodialysis) was 16, 17, and 15 days, respectively and was not statistically different. Many observations have reported discrimination of care for patients with CKD considered suboptimal candidates for aggressive management of their cardiac disease. In our study, medical therapy was achieved at high percentage and was comparable among groups of different kidney function. However, kidney disease seems to affect the management of patients with acute MI; percutaneous coronary angiography is not uniformly performed in patients with CKD and ESRD when compared with patients with normal kidney function. PMID- 26858530 TI - Targeted therapies with companion diagnostics in the management of breast cancer: current perspectives. AB - Breast cancer is a multifaceted disease exhibiting both intertumoral and intratumoral heterogeneity as well as variable disease course. Over 2 decades of research has advanced the understanding of the molecular substructure of breast cancer, directing the development of new therapeutic strategies against these actionable targets. In vitro diagnostics, and specifically companion diagnostics, have been integral in the successful development and implementation of these targeted therapies, such as those directed against the human epidermal growth factor receptor 2. Lately, there has been a surge in the development, commercialization, and marketing of diagnostic assays to assist in breast cancer patient care. More recently, multigene signature assays, such as Oncotype DX, MammaPrint, and Prosigna, have been integrated in the clinical setting in order to tailor decisions on adjuvant endocrine and chemotherapy treatment. This review provides an overview of the current state of breast cancer management and the use of companion diagnostics to direct personalized approaches in the treatment of breast cancer. PMID- 26858532 TI - Camarosporium arezzoensis on Cytisus sp., an addition to sexual state of Camarosporium sensu stricto. AB - During a study of saprobic fungi from Bagno di Cetica Province, Italy, we collected a pleosporoid ascomycete on stems of Cytisus sp. In morphology, our collection is similar to Cucurbitaria species, but molecular analysis of SSU, LSU and ITS genes reveals it can be referred to Camarosporium. In this study we compare all other Cucurbitaria species from Cytisus sp. and based on both morphology and molecular data, we introduce our collection as a new species in Camarosporium viz. C. arezzoensis. PMID- 26858531 TI - Melatonin and cortisol profiles in late midlife and their association with age related changes in cognition. AB - Previous studies have reported an association between circadian disturbances and age-related cognitive impairment. The aim was to study the 24-hour profiles of melatonin and cortisol in relation to cognitive function in middle-aged male subjects. Fifty healthy middle-aged males born in 1953 were recruited from a population-based cohort based on previous cognitive assessments in young adulthood and late midlife. The sample included 24 cognitively high-functioning and 26 cognitively impaired participants. Saliva samples were collected every 4 hours over a 24-hour period and analyzed for cortisol and melatonin levels by immunoassay. All participants exhibited clear circadian rhythms of salivary melatonin and cortisol. Salivary melatonin concentrations had a nocturnal peak at approximately 4 am. The median nocturnal melatonin response at 4 am was significantly lower in the cognitively impaired group than in the high functioning group (-4.6 pg/mL, 95% CI: -7.84, -1.36, P=0.006). The 24-hour mean melatonin concentration (high-functioning group: 4.80+/-0.70 pg/mL, vs cognitively impaired group: 4.81+/-0.76 pg/mL; P>0.05) (or the area under the curve, AUC) was not significantly different between the two groups. Cortisol levels were low during the night, and peaked at approximately 8 am. Median cortisol concentrations were similar at all times, as were the 24-hour mean cortisol concentrations and AUC. To the best of our knowledge, ours is the first study to assess circadian measures (ie, melatonin and cortisol) in healthy middle aged men with different cognitive trajectories in midlife. We found evidence of altered circadian rhythms with a reduced nocturnal melatonin response at 4 am in men with cognitive impairment. The 24-hour concentration and AUC of melatonin and cortisol were similar in the cognitively high-functioning group and in the cognitively impaired. PMID- 26858533 TI - A potential anti-inflammation activity and depigmentation effect of Lespedeza bicolor extract and its fractions. AB - Postinflammatory hyperpigmentation (PIH) is an acquire hypermelanosis after cutaneous inflammation and injury. The aim of the present study was to investigate a natural ingredient with the anti-inflammatory and depigmentation activities into possible applications of postinflammatory hyperpigmentation. Methanol extracts of Lespedeza bicolor and its various fractions inhibited LPS induced NO production in RAW 264.7 macrophages in a concentration-dependent manner. In particular, the ethyl acetate fraction was shown to be inhibition of NO production (89%) and down-regulation of iNOS mRNA without causing cytotoxicity. In addition, ethyl acetate fraction significantly attenuated LPS induced NF-kappaB activation (P < 0.05), indicating the anti-inflammatory activity due to NF-kappaB inhibition. Moreover, extracts, mainly ethyl acetate fraction, exhibited not only DPPH free radical scavenging activity (IC50, 112.45 MUg/mL) with 4 times lower activity than ascorbic acid, but also anti-tyrosinase activity (IC50, 1 MUg/mL) with a similar activity to arbutin showing a competitive inhibitor. Furthermore, vitexin and haginins A, B and C were identified through LC-MS analysis as potential compounds responsible for these effects. These results suggest that L. bicolor extract have anti-inflammatory, antioxidant activities and tyrosinase inhibitory effect and it might be used in the management of postinflammatory pigmentation through inhibition of pathogenic process involved in hyperpigmentation. PMID- 26858534 TI - Antioxidative and cytotoxic potential of some Chenopodium L. species growing in Poland. AB - The cytotoxic and antioxidant properties of lipophilic compounds extracted from different parts of four Chenopodium L. (Chenopodium album, Chenopodium hybridum, Chenopodium rubrum and Chenopodium urbicum) species were evaluated. The highest phenolic content was found in herb and seeds of all examined plants. Large amounts of free polyphenols were observed in herb extracts of C. album (3.36 mg/g DW), seeds of C. urbicum (3.87 mg/g DW) and roots of C. urbicum (1.52 mg/g DW). The cytotoxic activities of the extracts were assessed against human lung carcinoma A-549 and ovarian carcinoma TOV-112D and normal human fibroblast cell lines. Our study demonstrated that the extracts from the herb of C. rubrum and C. urbicum had the best antioxidant effect of all the extracts analyzed. Most of the extracts tested exhibited low cytotoxicity. However, the extracts from herb and seeds of C. album and C. hybridum showed the significant antiproliferative effect on the TOV-112 cell line. It can be concluded that antioxidant activity and phenolic composition differ mainly between plant parts and are quite similar between the plants, when the same plant part is analyzed. Thus, the Chenopodium extracts could be used as a readily accessible source of natural antioxidants, and may be used in the pharmaceutical industry and for food supplements production. PMID- 26858535 TI - Comparative growth, cross stress resistance, transcriptomics of Streptococcus pyogenes cultured under low shear modeled microgravity and normal gravity. AB - Streptococcus pyogenes is commonly found on pharynx, mouth and rarely on skin, lower gastrointestinal tract. It is a potential pathogen causing tonsillitis, pneumonia, endocarditis. The present study was undertaken to study the effects of low shear modeled microgravity on growth, morphology, antibiotic resistance, cross-stress resistance to various stresses and alteration in gene expression of S. pyogenes. The growth analysis performed using UV-Visible spectroscopy indicated decrease in growth of S. pyogenes under low shear modeled microgravity. Morphological analysis by Bio-transmission electron microscopy (TEM), Bio scanning electron microscopy (SEM) did not reveal much difference between normal and low shear modeled microgravity grown S. pyogenes. The sensitivity of S. pyogenes to antibiotics ampicillin, penicillin, streptomycin, kanamycin, hygromycin, rifampicin indicates that the bacterium is resistant to hygromycin. Further S. pyogenes cultured under low shear modeled microgravity was found to be more sensitive to ampicillin and rifampicin as compared with normal gravity grown S. pyogenes. The bacteria were tested for the acid, osmotic, temperature and oxidative cross stress resistances. The gene expression of S. pyogenes under low shear modeled microgravity analyzed by microarray revealed upregulation of 26 genes and down regulation of 22 genes by a fold change of 1.5. PMID- 26858536 TI - Modulation of the antibiotic activity against multidrug resistant strains of 4 (phenylsulfonyl) morpholine. AB - The compound 4-(Phenylsulfonyl) morpholine belongs to the class of sulfonamides, which are widely used in the treatment of a large number of diseases caused by microorganisms. This compound has a morpholine group, which is also known for its antimicrobial properties. The aim of the present study was to investigate the antimicrobial and modulating activity of 4-(Phenylsulfonyl) morpholine against standard and multi-resistant strains of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and strains of the fungi Candida albicans, C. tropicalis and C. krusei. Antimicrobial activity was assessed based on the minimum inhibitory concentration (MIC) using the microdilution method. MIC was ?1024 MUg/mL for all microorganisms. Regarding modulating activity, the most representative effect occurred with the combination of 4-(Phenylsulfonyl) morpholine at a concentration of 128 MUg/mL (MIC 1/8) and amikacin against P. aeruginosa 03, with a reduction in MIC from 312.5 to 39.06 MUg/mL. PMID- 26858537 TI - Bioremediation of adverse impact of cadmium toxicity on Cassia italica Mill by arbuscular mycorrhizal fungi. AB - Cassia italica Mill is an important medicinal plant within the family Fabaceae. Pot experiment was conducted to evaluate cadmium stress induced changes in physiological and biochemical attributes in C. italica with and without arbuscular mycorrhizal fungi (AMF). Cadmium stressed plant showed reduced chlorophyll pigment and protein content while AMF inoculation enhanced the chlorophyll and protein content considerably. AMF also ameliorated the cadmium stress induced reduction in total chlorophyll and protein contents by 19.30% and 38.29%, respectively. Cadmium stress enhanced lipid peroxidation while AMF inoculation reduced lipid peroxidation considerably. Increase in proline and phenol content was observed due to cadmium stress and AMF inoculation caused a further increase in proline and phenol content ensuring better growth under stressed conditions. AMF alone also enhanced proline and phenol content. Activity of antioxidant enzymes enhanced under cadmium treatment and AMF inoculation further enhanced their activity thereby strengthening the antioxidant system. Enhanced activities of antioxidants and increased accumulation of osmolytes help plants to avoid damaging impact of oxidative damage. The research has shown that AMF inoculation mitigated the negative impact of stress by reducing the lipid peroxidation and enhancing the antioxidant activity. The present study strongly supports employing AMF as the biological mean for enhancing the cadmium stress tolerance of C. italica. PMID- 26858538 TI - Comparative studies for serodiagnosis of haemorrhagic septicaemia in cattle sera. AB - Haemorrhagic septicaemia caused by Pasteurella multocida is a major epizootic disease in cattle and buffaloes in developing countries with high morbidity and mortality rate. In the present study, a total of 88 P. multocida isolates were isolated from 256 nasopharyngeal swabs and lung tissues samples (34.4%) during the period from January, 2013 to March, 2014 from different governorates located in Egypt. Dead calves showed the highest percentage of P. multocida isolation followed by the emergency slaughtered calves, diseased calves then apparently healthy ones. These isolates were confirmed as P. multocida microscopically, biochemically by traditional tests and by API 20E commercial kit then by PCR. The percentages of positive serum samples using somatic antigen and micro agglutination test at 1/1280 diluted serum were 10%, 54.49% and 0% in apparently healthy, diseased and emergency slaughtered samples, respectively whereas, the percentages using capsular antigen and indirect haemagglutination test were 40%, 60.89% and 60% in apparently healthy, diseased and emergency slaughtered samples, respectively. The ELISA showed the highest sensitivity for diagnosing P. multocida in apparently healthy, diseased and emergency slaughtered animals with percentages of 42%; 92.9% and 80%, respectively. The obtained results revealed that the ELISA using capsular antigen of P. multocida is a more sensitive and specific serological test for diagnosis of haemorrhagic septicaemia. PMID- 26858539 TI - Comparative pharmacokinetics of a proliposome formulation of Ginkgo biloba extract and Ginaton in rats by a sensitive ultra performance liquid chromatography-tandem mass spectrometry method. AB - As a novel oral drug delivery system, proliposome was applied to improve the solubility of active components of Ginkgo biloba extract (GbE). There are currently few reports focusing on the pharmacokinetic characteristics of proliposome of GbE (GbP). A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the simultaneous quantification of active components of GbP and a commercial tablet product (Ginaton) in rat plasma was developed and successfully validated. The method was applied to the comparative pharmacokinetic evaluation of GbP and Ginaton in rat plasma. The results indicated that GbP has a significant effect on absorption, elimination and bioavailability of flavonoids and terpenoid lactones in comparison with Ginaton. The obtained results would be helpful for evaluating the absorption mechanism in the gastrointestinal tract in pharmacokinetic level and guiding the development of the novel oral drug delivery system. PMID- 26858540 TI - Prediction of complex super-secondary structure betaalphabeta motifs based on combined features. AB - Prediction of a complex super-secondary structure is a key step in the study of tertiary structures of proteins. The strand-loop-helix-loop-strand (betaalphabeta) motif is an important complex super-secondary structure in proteins. Many functional sites and active sites often occur in polypeptides of betaalphabeta motifs. Therefore, the accurate prediction of betaalphabeta motifs is very important to recognizing protein tertiary structure and the study of protein function. In this study, the betaalphabeta motif dataset was first constructed using the DSSP package. A statistical analysis was then performed on betaalphabeta motifs and non-betaalphabeta motifs. The target motif was selected, and the length of the loop-alpha-loop varies from 10 to 26 amino acids. The ideal fixed-length pattern comprised 32 amino acids. A Support Vector Machine algorithm was developed for predicting betaalphabeta motifs by using the sequence information, the predicted structure and function information to express the sequence feature. The overall predictive accuracy of 5-fold cross-validation and independent test was 81.7% and 76.7%, respectively. The Matthew's correlation coefficient of the 5-fold cross-validation and independent test are 0.63 and 0.53, respectively. Results demonstrate that the proposed method is an effective approach for predicting betaalphabeta motifs and can be used for structure and function studies of proteins. PMID- 26858541 TI - Monitoring of trace metals in tissues of Wallago attu (lanchi) from the Indus River as an indicator of environmental pollution. AB - We aimed to assess the bioaccumulation of selected four trace metals (Cd, Ni, Zn and Co) in four tissues (muscles, skin, gills and liver) of a freshwater fish Wallago attu (lanchi) from three different sites (upstream, middle stream and downstream) of the Indus River in Mianwali district of Pakistan. Heavy metal contents in water samples and from different selected tissues of fish were examined by using flame atomic absorption spectrometry. The data were statistically compared to study the effects of the site and fish organs and their interaction on the bioaccumulation pattern of these metals at P < 0.05. In W. attu the level of cadmium ranged from 0.004 to 0.24; nickel 0.003-0.708; cobalt 0.002-0.768 and zinc 47.4-1147.5 MUg/g wet weight. The magnitude of metal bioaccumulation in different organs of fish species had the following order gills > liver > skin > muscle. The order of bioaccumulation of these metals was Ni < Zn < Co < Cd. Heavy metal concentrations were increased during the dry season as compared to the wet season. The results of this study indicate that freshwater fish produced and marketed in Mianwali have concentrations below the standards of FEPA/WHO for these toxic metals. PMID- 26858542 TI - Characterization of the plant growth promoting bacterium, Enterobacter cloacae MSR1, isolated from roots of non-nodulating Medicago sativa. AB - The aim of the present study was to characterize the endophytic bacterial strain designated MSR1 that was isolated from inside the non-nodulating roots of Medicago sativa after surface-sterilization. MSR1 was identified as Enterobacter cloacae using both 16S rDNA gene sequence analysis and API20E biochemical identification system (Biomerieux, France). Furthermore, this bacterium was characterized using API50CH kit (Biomerieux, France) and tested for antibacterial activities against some food borne pathogens. The results showed that E. cloacae consumed certain carbohydrates such as glycerol, d-xylose, d-maltose and esculin melibiose as a sole carbon source and certain amino acids such as arginine, tryptophan ornithine as nitrogen source. Furthermore, MSR1 possessed multiple plant-growth promoting characteristics; phosphate solubility, production of phytohormones acetoin and bioactive compounds. Inoculation of Pisum sativum with MSR1 significantly improved the growth parameters (the length and dry weight) of this economically important grain legume compared to the non-treated plants. To our knowledge, this is the first report addressing E. cloacae which exist in roots of alfalfa growing in Al-Ahsaa region. The results confirmed that E. cloacae exhibited traits for plant growth promoting and could be developed as an eco-friendly biofertilizer for P. sativum and probably for other important plant species in future. PMID- 26858543 TI - Development of spermatic granuloma in albino rats following administration of water extract of Heliotropium bacciferum Forssk. AB - A spermatic granuloma is a chronic inflammatory reaction produced in response to extravasated sperm within the intertubular connective tissue. The present study investigates the possible toxic effects of water extract of Heliotropium bacciferum on the reproductive system of male albino rats and the associated potential for the development of spermatic granulomas. H. bacciferum is a herbal plant used in traditional medicine and reported to have cytotoxic effects due to pyrrolizidine alkaloids. Histological examinations revealed no changes in the tissues of the testes, although, some changes were detected in the cauda epididymis, the most important of which was the development of small lesions of spermatic granulomas. Clear gaps were observed between the epithelial linings of the epididymal tubules. PMID- 26858544 TI - New approach for determination of an optimum honeybee colony's carrying capacity based on productivity and nectar secretion potential of bee forage species. AB - The present study was carried out to determine an optimum honeybee colony's carrying capacity of selected valleys dominated by Ziziphus spina-christi and Acacia tortilis in the Al-Baha region, Kingdom of Saudi Arabia. The study was conducted based on the assessment of the number of colonies kept, their productivities and the existing productive bee forage resources in the target valleys with its economic implication. In the existing beekeeping practice, the average number of managed honeybee colonies introduced per square kilometer was 530 and 317 during the flowering period of Z. spina-christi and A. tortilis, respectively. Furthermore, the overall ratios of productive bee forage plants to the number of honeybee colonies introduced were 0.55 and 11.12 to Ziziphus trees and A. tortilis shrubs respectively. In the existing situation the average honey production potential of 5.21 and 0.34 kg was recorded per Ziziphus and A. tortilis plants per flowering season, respectively. The present study, revealed that the number of honeybee colonies introduced in relation to the existing bee forage potential was extremely overcrowding which is beyond the carrying capacity of bee forage resources in selected valleys and it has been observed to affect the productivities and subsequent profitability of beekeeping. The study infers that, by keeping the optimum honeybee colony's carrying capacity of valleys (88 traditional hives/km(2) or 54 Langstroth hives/km(2) in Ziziphus field and 72 traditional hives/km(2) or 44 Langstroth hives/km(2) in A. tortilis field), profitability of beekeeping can be boosted up to 130.39% and 207.98% during Z. spina-christi and A. tortilis, flowering seasons, respectively. PMID- 26858545 TI - Analysis of CD95 and CCR7 expression on circulating CD4(+) lymphocytes revealed disparate immunoregulatory potentials in systemic lupus erythematosus. AB - Emerging data have implicated a critical role for CD4 in the pathogenesis of systemic lupus erythematosus (SLE). This study was designed to delineate the contribution of CD4(+) T cells in the pathogenesis of SLE disease. Forty-four patients (3 male: 41 female) and 20 healthy volunteers (4 male: 16 female) were included in the study. CD4(+) lymphocytes analysis was done using three-color flow cytometry with antibodies against human-CD95, a prototype cell death receptor, and the chemokine receptor-7 (CCR7) after gating for lymphocytes based on the forward and side scatter. Serum levels of IL-6, IL-12, IL-17, TNF-alpha and IL-10 cytokines were assayed using ELISA. Disease activity was assessed using the SLE disease activity index (SLEDAI). Based on the expression of CCR7 and CD95, CD4(+) lymphocytes were subdivided into three particular subsets; CD4(+)CD95(+)CCR7(+) cells, CD4(+)CD95(-)CCR7(+) cells and CD4(+)CD95(+)CCR7(-) cells. Percentage of CD4(+)CD95(+)CCR7(+) cell subset was significantly higher in patients with SLE with active disease (SLEDAI > 6) and inactive (SLEDAI < 6) as compared with controls (P = 0.005), and it showed a significant positive correlation with ANA titer (P = 0.01), and a negative correlation with WBCs count (P = 0.001). CD4(+)CD95(+)CCR7(-) cell subset was significantly higher in active SLE patients in comparison to patients with inactive disease and controls (P = 0.05, P = 0.005 respectively), and it correlates positively with SLEDAI, IL-6 and IL-17 levels (P = 0.001, 0.05, 0.01 respectively), and negatively with blood WBCs counts (P = 0.001). The third CD4(+)CD95(-)CCR7(+)cell subset was found significantly lower in SLE patients compared with controls, and it was found negatively correlated with IL-10, IL-6, and IL-17. The results show that CD4(+)CD95(+)subset lacking expression of CCR7 is associated with cell mediated inflammatory response as manifested by its correlation with signs of inflammation, inflammatory cytokines and disease activity index. Whereas, CD4(+)CD95(+)CCR7(+) correlate more with antibody immune responses as manifested by association with serum ANA. These data suggest disparate roles of these cell subsets in the pathophysiology of SLE. A better understanding of the characteristics of CD4 cell subsets may shed light on the pathogenesis of autoimmune diseases, particularly SLE. PMID- 26858546 TI - Morphological and morphometrical analysis of Heterodera spp. populations in Jordan. AB - Phenotypic diversity of five Jordanian populations of cyst nematodes, Heterodera spp. collected from five regions from Jordan (Ar-Ramtha, Madaba, Dana, Al-Karak, and Jerash) was investigated. Soil samples were collected from one representative field in each region. Morphological and morphometrical characteristics revealed that Heterodera latipons is dominated in cereal fields at Ar-Ramtha, Madaba, Dana and Al-Karak regions and Heterodera schachtii in Jerash. Cysts populations from all cereal fields had bifenestrate vulval cone and a strong underbridge. Wherever, cysts of the cabbage population had ambifenestrate vulval cone with long vulval slit. The bullae were absent in Ar-Ramtha, Madaba and Dana populations, but present in Al-Karak and Jerash. Based on 12 morphometrical characters, the first three functions in canonical discriminant analysis accounted 99.3% of the total variation. Distance from dorsal gland duct opening to stylet base, underbridge length, a = L/W (body length/midbody width) and length of hyaline tail tip had strong and significant contributions in the first function. While the second function was strongly influenced by length of hyaline tail, fenestral length, fenestral width and tail length. However, the third canonical discriminate function was found to be influenced by stylet length, fenestral length, a = L/W (body length/midbody width) and underbridge width. The graphical representation of the distribution of the samples showed that the first canonical discriminant function clearly separated H. schachtii from Jerash from other populations. Whereas, H. latipons collected from Madaba and Dana were clearly separated in the second function. The results indicated that differences at morphological and morphometrical levels revealed diverse populations of Heterodera spp. in Jordan. PMID- 26858547 TI - Morphological cladistic analysis of eight popular Olive (Olea europaea L.) cultivars grown in Saudi Arabia using Numerical Taxonomic System for personal computer to detect phyletic relationship and their proximate fruit composition. AB - Varietal identification of olives is an intrinsic and empirical exercise owing to the large number of synonyms and homonyms, intensive exchange of genotypes, presence of varietal clones and lack of proper certification in nurseries. A comparative study of morphological characters of eight olive cultivars grown in Saudi Arabia was carried out and analyzed using NTSYSpc (Numerical Taxonomy System for personal computer) system segregated smaller fruits in one clade and the rest in two clades. Koroneiki, a Greek cultivar with a small sized fruit shared arm with Spanish variety Arbosana. Morphologic analysis using NTSYSpc revealed that biometrics of leaves, fruits and seeds are reliable morphologic characters to distinguish between varieties, except for a few morphologically very similar olive cultivars. The proximate analysis showed significant variations in the protein, fiber, crude fat, ash and moisture content of different cultivars. The study also showed that neither the size of fruit nor the fruit pulp thickness is a limiting factor determining crude fat content of olives. PMID- 26858548 TI - Photoactivated disinfection (PAD) of dental root canal system - An ex-vivo study. AB - AIM: To investigate the efficacy of photo activated disinfection (PAD) in reducing colony-forming unit (CFU) counts of Enterococcus faecalis (E. faecalis) in infected dental root canals. The study compared the efficacy of PAD with conventional endodontic treatment (CET) and also a combination of CET along with PAD. MATERIAL AND METHODS: 53 maxillary incisors were taken for the study. Teeth were divided into 3 groups, CET (Group I) (n = 11), PAD (Group II) (n = 21), and a combination of CET and PAD (Group III) which consisted of (n = 21) samples, Group II and Group III were further divided into 2 subgroups, Group IIa, IIb and Group IIIa, IIIb. Strains of E. faecalis were inoculated in all the root canals. CET group samples were treated by chemo-mechanical preparation (CMP) alone, PAD samples were treated with laser alone at 2 different exposure time (4 min and 2 min). In the combination treatment, samples were treated initially by CET and then by PAD for a time period of 4 min and 2 min. Contents of the root canal were aspirated, diluted and plated in Tryptone Soya Broth (TSB) and plates were incubated for 24 h to observe the bacterial regrowth. RESULTS: Showed PAD used along with CMP reduced the bacterial load of E. faecalis by 99.5% at 4 min and 98.89% at 2 min. CONCLUSION: PAD may be an adjunctive procedure to kill residual bacteria in the dental root canal systems after standard endodontic root canal preparation. PMID- 26858550 TI - Ecological aspects of the horned viper, Cerastes cerastes gasperettii in the central region of Saudi Arabia. AB - Feeding ecology of any species can help us to understand its natural history, ecological requirements and approaches involved in searching for food. Feeding ecology and sexual dimorphism in the horned viper, Cerastes cerastes gasperetti collected from the Al-Thumama area, central region of Saudi Arabia was described. The gut content of Cerastes c. gasperetti mainly consisted of rodents (70%) in addition to arthropods (15%) and lizards (10%). Least sexual size dimorphism was noticed in the species in terms of total length. Significant difference was noticed between males and females in terms of two correlation points vent tail length (VT) and total length (TL) with the males attaining a larger size (P < 0.05). The mean number of the dorsal body scales, ventrals and subcaudals for the females was 102, 156 and 33 scales respectively which were significantly different from respective ones in males 95, 160 and 38 scales. There are many aspects of the feeding of this snake that remain unknown and further studies are clearly needed. PMID- 26858549 TI - Insertion and deletion polymorphism in the alpha-2B adrenoceptor gene in pregnant women ripens gestational diabetes mellitus. AB - There are no earlier studies that reported the association of the 12Glu9 polymorphism in the alpha-2B adrenoceptor (ADRA2B) gene with gestational diabetes mellitus (GDM). We examined the potential association between the ADRA2B gene insertion/deletion (I/D) polymorphism in the Saudi population with GDM. Pregnant women with GDM have been reported to exhibit the same susceptibility as that observed in type 2 diabetes mellitus (T2DM). We have selected I/D polymorphism of the ADRA2B gene located in chromosome 2q11.1 that has been extensively related to T2DM and cardiovascular diseases. This case-control study was conducted with 200 GDM and 300 non-GDM pregnant women. Genotyping of I/D polymorphism was performed by conventional PCR method. Biochemical analyses were found to be significantly different between GDM and non-GDM subjects (p < 0.05). Genotype (ID + DD vs II, p = 0.0002) and allele (D vs I, p = 0.0002) frequencies of the 12Glu9 polymorphism were found to be statistically significant. However, a significant difference was found between allele and genotypes of I/D polymorphism of the ADRA2B gene or the clinical characteristics of the subjects. Our results obtained in this study indicate the ADRA2B gene in the Saudi women was associated with the development of GDM. PMID- 26858551 TI - Unraveling the efficiency of RAPD and SSR markers in diversity analysis and population structure estimation in common bean. AB - Increase in food production viz-a-viz quality of food is important to feed the growing human population to attain food as well as nutritional security. The availability of diverse germplasm of any crop is an important genetic resource to mine the genes that may assist in attaining food as well as nutritional security. Here we used 15 RAPD and 23 SSR markers to elucidate diversity among 51 common bean genotypes mostly landraces collected from the Himalayan region of Jammu and Kashmir, India. We observed that both the markers are highly polymorphic. The discriminatory power of these markers was determined using various parameters like; percent polymorphism, PIC, resolving power and marker index. 15 RAPDs produced 171 polymorphic bands, while 23 SSRs produced 268 polymorphic bands. SSRs showed a higher PIC value (0.300) compared to RAPDs (0.243). Further the resolving power of SSRs was 5.241 compared to 3.86 for RAPDs. However, RAPDs showed a higher marker index (2.69) compared to SSRs (1.279) that may be attributed to their higher multiplex ratio. The dendrograms generated with hierarchical UPGMA cluster analysis grouped genotypes into two main clusters with various degrees of sub clustering within the cluster. Here we observed that both the marker systems showed comparable accuracy in grouping genotypes of common bean according to their area of cultivation. The model based STRUCTURE analysis using 15 RAPD and 23 SSR markers identified a population with 3 sub-populations which corresponds to distance based groupings. High level of genetic diversity was observed within the population. These findings have further implications in common bean breeding as well as conservation programs. PMID- 26858552 TI - Urinary catheter indwelling clinical pathogen biofilm formation, exopolysaccharide characterization and their growth influencing parameters. AB - Self-reproducing microbial biofilm community mainly involved in the contamination of indwelling medical devices including catheters play a vital role in nosocomial infections. The catheter-associated urinary tract infection (CA-UTI) causative Staphylococcus aureus, Enterobacter faecalis, and Pseudomonas aeruginosa were selectively isolated, their phenotypic as well as genotypic biofilm formation, production and monomeric sugar composition of EPS as well as sugar, salt, pH and temperature influence on their in vitro biofilm formation were determined. From 50 culture positive urinary catheters S. aureus (24%), P. aeruginosa (18%), E. faecalis (14%) and others (44%) were isolated. The performed assays revealed their varying biofilm forming ability. The isolated S. aureus ica, E. faecalis esp, and P. aeruginosa cup A gene sequencing and phylogenetic analysis showed their close branching and genetic relationship. The analyzed sugar, salt, pH, and temperature showed that the degree of CA-UTI isolates biofilm formation is an environmentally sensitive process. EPS monosaccharide HPLC analysis showed the presence of neutral sugars (ng/MUl) as follows: glucose (P. aeruginosa: 44.275; E. faecalis: 4.23), lactose (P. aeruginosa: 7.29), mannitol (P. aeruginosa: 2.53; S. aureus: 2.62; E. faecalis: 2.054) and maltose (E. faecalis: 7.0042) revealing species-specific presence and variation. This study may have potential clinical relevance for the easy diagnosis and management of CA-UTI. PMID- 26858553 TI - Biology and evolution of life science. PMID- 26858555 TI - A new mathematical evaluation of smoking problem based of algebraic statistical method. AB - Smoking problem is considered as one of the hot topics for many years. In spite of overpowering facts about the dangers, smoking is still a bad habit widely spread and socially accepted. Many people start smoking during their gymnasium period. The discovery of the dangers of smoking gave a warning sign of danger for individuals. There are different statistical methods used to analyze the dangers of smoking. In this study, we apply an algebraic statistical method to analyze and classify real data using Markov basis for the independent model on the contingency table. Results show that the Markov basis based classification is able to distinguish different date elements. Moreover, we check our proposed method via information theory by utilizing the Shannon formula to illustrate which one of these alternative tables is the best in term of independent. PMID- 26858554 TI - Near infrared spectroscopy coupled with radial basis function neural network for at-line monitoring of Lactococcus lactis subsp. fermentation. AB - In our previous work, partial least squares (PLSs) were employed to develop the near infrared spectroscopy (NIRs) models for at-line (fast off-line) monitoring key parameters of Lactococcus lactis subsp. fermentation. In this study, radial basis function neural network (RBFNN) as a non-linear modeling method was investigated to develop NIRs models instead of PLS. A method named moving window radial basis function neural network (MWRBFNN) was applied to select the characteristic wavelength variables by using the degree approximation (Da) as criterion. Next, the RBFNN models with selected wavelength variables were optimized by selecting a suitable constant spread. Finally, the effective spectra pretreatment methods were selected by comparing the robustness of the optimum RBFNN models developed with pretreated spectra. The results demonstrated that the robustness of the optimal RBFNN models were better than the PLS models for at line monitoring of glucose and pH of L. lactis subsp. fermentation. PMID- 26858557 TI - Mechanical characteristics of antibacterial epoxy resin adhesive wood biocomposites against skin disease. AB - Moldy wood can cause some skin disease. However epoxy resin adhesive (EP) can inhibit mold growth. Therefore, antibacterial EP/wood biocomposites were reinforced and analyzed by the nonlinear finite element. Results show that glass fiber cloth and aluminum foil have the obvious reinforced effect under flat pressure, but this was not the case under side pressure. And when the assemble pattern was presented in 5A way, the strengthening effect was better. The nonlinear finite element showed that the aluminum foil and glass fiber cloth have the obvious reinforced effect. The mutual influence and effect of span, thickness and length on the ultimate bearing capacity of specimen were studied. And the simulation results agreed with the test. It provided a theoretical basis on the preparation of antibacterial EP/wood biocomposites against skin disease. PMID- 26858556 TI - Improvement of oral availability of ginseng fruit saponins by a proliposome delivery system containing sodium deoxycholate. AB - Ginseng fruit saponins (GFS) extracted from the ginseng fruit are the bioactive triterpenoid saponin components. The aim of the present study was to develop a drug delivery system called proliposome using sodium deoxycholate (NaDC) as a bile salt to improve the oral bioavailability of GFS in rats. The liposomes of GFS were prepared by a conventional ethanol injection and formed the solid proliposomes (P-GFS) using spray drying method on mannitol carriers. The formulation of P-GFS was optimized using the response surface methodology. The physicochemical properties of liposome suspensions including encapsulation efficiency, in vitro drug release studies, particle size of the reconstituted liposome were tested. The solid state characterization studies using the method of Field emission-scanning electron microscope (FE-SEM), Fourier transform infrared (FT-IR) and Differential scanning colorimetric (DSC) were tested to study the molecular state of P-GFS and to indicate the interactions among the formulation ingredients. In vitro studies showed a delayed release of ginsenoside Re (GRe). In vivo studies were carried out in rats. The concentrations of GRe in plasma of rats and its pharmacokinetic behaviors after oral administration of GFS, Zhenyuan tablets (commercial dosage form of GFS) and P-GFS were studied using ultra performance liquid chromatography tandem mass spectrometry. It was founded that the GRe concentration time curves of GFS, Zhenyuan tablets and P-GFS were much more different in rats. Pharmacokinetic behaviors of P-GFS showed a second absorption peak on the concentration time curve. The pharmacokinetic parameters of GFS, Zhenyuan tablets, P-GFS in rats were separately listed as follows: T max 0.25 h, C max 474.96 +/- 66.06 ng/ml and AUC0-infinity 733.32 +/- 113.82 ng/ml h for GFS; T max 0.31 +/- 0.043 h, C max 533.94 +/- 106.54 ng/ml and AUC0-infinity 1151.38 +/- 198.29 ng/ml h for Zhenyuan tablets; T max 0.5 h, C max 680.62 +/- 138.051 ng/ml and AUC0-infinity 2082.49 +/- 408.33 ng/ml h for the P GFS. The bioavailability of P-GFS was nearly 284% and 181% of the GFS and Zhengyuan tablets respectively. In conclusion, the proliposomes significantly enhanced the drug bioavailability, absorption in the gastrointestinal tract and decreased its elimination time of GRe in rats and could be selectively applied for oral delivery of GFS. PMID- 26858558 TI - Review on antibacterial characteristics of bridge engineering biomaterials. AB - This review summarizes the research on timber construction materials used in bridge construction. It focuses on the application of antiseptic treatments and the use of timber engineering materials in decks and bridges. This review also provides an overview on the future research and prospects of engineered timber materials. PMID- 26858559 TI - Review on antibacterial biocomposites of structural laminated veneer lumber. AB - In this review, the characteristics and applications of structural laminated veneer lumber made from planted forest wood is introduced, and its preparation is explained, including various tree species and slab qualities, treatments for multiple effects and reinforced composites. The relevant factors in the bonding technology and pressing processes as well as the mechanical properties, research direction and application prospects of structural laminated veneer lumber made from planted forest wood are discussed. PMID- 26858560 TI - Effects of verbenalin on prostatitis mouse model. AB - The aim of this study was to observe the treatment characteristics of verbenalin on a prostatitis mouse model. Give Xiaozhiling injection in the prostate locally to make a prostatitis mouse model. High, medium and low doses of verbenalin were each given to different mouse groups. The amount of water was determined in 14th, 28th. The number of white cells and lecithin corpuscle density in prostatic fluid were determined. Morphological changes in the prostate, testis, epididymis and kidney were detected. Compared with the model control group, the mice treated with high, medium and low doses of verbenalin had significantly increased amounts of water, and prostate white blood cell count and prostate volume density (Vv) were decreased significantly, the density of lecithin corpuscle score increased, and pathologic prostatitis changes were significantly reduced. Pathological change in the testis was significantly reduced and the change in the epididymis was obviously reduced. The thymic cortex thickness and the number of lymphocytes increased significantly and could reduce the renal pathological changes in potential. Verbenalin has a good therapeutic effect on the prostatitis mouse model. PMID- 26858562 TI - One-step synthesis of interpenetrating network hydrogels: Environment sensitivities and drug delivery properties. AB - A novel interpenetrating network hydrogel for drug controlled release, composed of modified poly(aspartic acid) (KPAsp) and carboxymethyl chitosan (CMCTS), was prepared in aqueous system. The surface morphology and composition of hydrogels were characterized by SEM and FTIR. The swelling properties of KPAsp, KPAsp/CMCTS semi-IPN and KPAsp/CMCTS IPN hydrogels were investigated and the swelling dynamics of the hydrogels was analyzed based on the Fickian equation. The pH, temperature and salt sensitivities of hydrogels were further studied, and the prepared hydrogels showed extremely sensitive properties to pH, temperature, the ionic salts kinds and concentration. The results of controlled drug release behaviors of the hydrogels revealed that the introduction of IPN observably improved the drug release properties of hydrogels, the release rate of drug from hydrogels can be controlled by the structure of the hydrogels and pH value of the external environment, a relative large amount of drug released was preferred under simulated intestinal fluid. These results illustrated high potential of the KPAsp/CMCTS IPN hydrogels for application as drug carriers. PMID- 26858561 TI - The effect and action mechanism of resveratrol on the vascular endothelial cell by high glucose treatment. AB - To investigate the effect and action mechanism of resveratrol on the vascular endothelial cell by high glucose treatment. Primarily cultured human umbilical vein endothelial cells (HUVECs) were pretreated by resveratrol (0.2 MUmol/L) and holding for 6 h, and then cultured in Dulbecco Modified Eagle Medium (DMEM) within 0.45 mmol/L of palmimte acid and 32.8 mmol/L of glucose, which is holding for 12 h. The cells were collected to analyze the expression of E-selected element. Supernatant of cultured cells, induced by 100 nmol/L insulin for 30 min, was used to analyze the nitric oxide content. Compared with normal control cells, the secretion of nitric oxide is stimulated by insulin decrease, however, the expression of E-selected element increased in HUVEC. Resveratrol treatment increased the secretion of nitric oxide stimulated by insulin and decreased the expression of E-selected element and partly counteracts the impairment of high glucose and palmitate acid on the function of endothelial cells. Resveratrol can improve and protect the function of high glucose and fatty acid cultured endothelial cell, and therefore may be a promising medicine in the prevention or therapy of diabetic macrovascular diseases. PMID- 26858564 TI - Mathematical model for adaptive evolution of populations based on a complex domain. AB - A mutation is ultimately essential for adaptive evolution in all populations. It arises all the time, but is mostly fixed by enzymes. Further, most do consider that the evolution mechanism is by a natural assortment of variations in organisms in line for random variations in their DNA, and the suggestions for this are overwhelming. The altering of the construction of a gene, causing a different form that may be communicated to succeeding generations, produced by the modification of single base units in DNA, or the deletion, insertion, or rearrangement of larger units of chromosomes or genes. This altering is called a mutation. In this paper, a mathematical model is introduced to this reality. The model describes the time and space for the evolution. The tool is based on a complex domain for the space. We show that the evolution is distributed with the hypergeometric function. The Boundedness of the evolution is imposed by utilizing the Koebe function. PMID- 26858563 TI - Field accumulation risks of heavy metals in soil and vegetable crop irrigated with sewage water in western region of Saudi Arabia. AB - Wastewater irrigated fields can cause potential contamination with heavy metals to soil and groundwater, thus pose a threat to human beings . The current study was designed to investigate the potential human health risks associated with the consumption of okra vegetable crop contaminated with toxic heavy metals. The crop was grown on a soil irrigated with treated wastewater in the western region of Saudi Arabia during 2010 and 2011. The monitored heavy metals included Cd, Cr, Cu, Pb and Zn for their bioaccumulation factors to provide baseline data regarding environmental safety and the suitability of sewage irrigation in the future. The pollution load index (PLI), enrichment factor (EF) and contamination factor (CF) of these metals were calculated. The pollution load index of the studied soils indicated their level of metal contamination. The concentrations of Ni, Pb, Cd and Cr in the edible portions were above the safe limit in 90%, 28%, 83% and 63% of the samples, respectively. The heavy metals in the edible portions were as follows: Cr > Zn > Ni > Cd > Mn > Pb > Cu > Fe. The Health Risk Index (HRI) was >1 indicating a potential health risk. The EF values designated an enhanced bio-contamination compared to other reports from Saudi Arabia and other countries around the world. The results indicated a potential pathway of human exposure to slow poisoning by heavy metals due to the indirect utilization of vegetables grown on heavy metal-contaminated soil that was irrigated by contaminated water sources. The okra tested was not safe for human use, especially for direct consumption by human beings. The irrigation source was identified as the source of the soil pollution in this study. PMID- 26858565 TI - Embryo apoptosis identification: Oocyte grade or cleavage stage? AB - Apoptosis is a programed cell death that is vital for tissue homeostasis. However, embryo apoptosis had been known to be related to embryo fragmentation which should be avoided in in vitro fertilization (IVF). The purpose of this study was to evaluate the relationship of embryo apoptosis with the grade of immature oocytes and cleavage stage of in vitro produced (IVP) cattle embryos. This study consisted of 345 oocytes collected through ovary slicing. Immature oocytes were graded as A, B and C. This grading was based on cumulus cell thickness and compactness. All oocytes then underwent an in vitro maturation (IVM) procedure. An IVF was done 24 h after IVM culture. Prior to staining, stage of cleaved embryos was determined and classified as either 2, 4, 8 or >8-cell embryo stage. Apoptosis status of cleaved IVP embryos was determined by using annexin V-FITC staining technique at 48 and 72 h post insemination (hpi). Apoptosis status for each embryo was classified as either early or late. The result showed that there was no significant difference (p > 0.05) of apoptosis status among grade A, B and C embryos. All grades of oocytes showed embryo apoptosis where 1.5% late apoptosis for grade A, 4.5% and 10.4% of early and late apoptosis for grade B and grade C. Early apoptosis was not seen in grade A embryo. We also noted no significant difference (p > 0.05) of apoptosis status between 2, 4, 8 and >8-cell embryo stage. Early apoptosis was also not seen in >8 cell stage. Even though there were no differences in apoptosis expression between the three classes, the cleavage rate of grade A oocytes was significantly higher (p < 0.01) than grade B and grade C. In conclusion, the apoptosis expression in the embryo can occur regardless of the oocyte quality and the cleavage stage of the embryo produced. PMID- 26858566 TI - Bioactivity studies and adhesion of human osteoblast (hFOB) on silicon-biphasic calcium phosphate material. AB - Surface reactivity of bioactive ceramics contributes in accelerating bone healing by anchoring osteoblast cells and the connection of the surrounding bone tissues. The presence of silicon (Si) in many biocompatible and bioactive materials has been shown to improve osteoblast cell adhesion, proliferation and bone regeneration due to its role in the mineralisation process around implants. In this study, the effects of Si-biphasic calcium phosphate (Si-BCP) on bioactivity and adhesion of human osteoblast (hFOB) as an in vitro model have been investigated. Si-BCP was synthesised using calcium hydroxide (Ca(OH)2) and phosphoric acid (H3PO4) via wet synthesis technique at Ca/P ratio 1.60 of material precursors. SiO2 at 3 wt% based on total precursors was added into apatite slurry before proceeding with the spray drying process. Apatite powder derived from the spray drying process was pressed into discs with O 10 mm. Finally, the discs were sintered at atmospheric condition to obtain biphasic hydroxyapatite (HA) and tricalcium phosphate (TCP) peaks simultaneously and examined by XRD, AFM and SEM for its bioactivity evaluation. In vitro cell viability of L929 fibroblast and adhesion of hFOB cell were investigated via AlamarBlue(r) (AB) assay and SEM respectively. All results were compared with BCP without Si substitution. Results showed that the presence of Si affected the material's surface and morphology, cell proliferation and cell adhesion. AFM and SEM of Si-BCP revealed a rougher surface compared to BCP. Bioactivity in simulated body fluid (SBF) was characterised by pH, weight gain and apatite mineralisation on the sample surface whereby the changes in surface morphology were evaluated using SEM. Immersion in SBF up to 21 days indicated significant changes in pH, weight gain and apatite formation. Cell viability has demonstrated no cytotoxic effect and denoted that Si-BCP promoted good initial cell adhesion and proliferation. These results suggest that Si-BCP's surface roughness (164 nm) was significantly higher than BCP (88 nm), thus enhancing the adhesion and proliferation of the osteoblast. PMID- 26858567 TI - In vitro importance of probiotic Lactobacillus plantarum related to medical field. AB - Lactobacillus plantarum is a Gram positive lactic acid bacterium commonly found in fermented food and in the gastro intestinal tract and is commonly used in the food industry as a potential starter probiotic. Recently, the consumption of food together with probiotics has tremendously increased. Among the lactic acid bacteria, L. plantarum attracted many researchers because of its wide applications in the medical field with antioxidant, anticancer, anti inflammatory, antiproliferative, anti-obesity and antidiabetic properties. The present study aimed to investigate the in vitro importance of L. plantarum toward medical applications. Moreover, this report short listed various reports related to the applications of this promising strain. In conclusion, this study would attract the researchers in commercializing this strain toward the welfare of humans related to medical needs. PMID- 26858568 TI - Determination of free amino acids in burley tobacco by high performance liquid chromatography. AB - A reversed-phase high performance liquid chromatographic method was developed for determining free amino acids in burley tobacco. The test was done by OPA/3 mercaptopropionic acid as the pre-column derivatizing reagent. Chromatographic column was Elitte C(18) column (4.6 mm * 250 mm i.d., 5 MUm). Mobile phase A was 18 mol/l NaAc (pH7.2) including 0.002%(v/v) triethylamine and 0.3%(v/v) furanidine. Mobile phase B was 100 mol/l NaAc (pH7.2)-acetonitrile-methanol (v/v = 1:2:2). The column temperature was 40 degrees C and the flow rate was 1.0 ml/min. The fluorescence detector was used with 350 nm excitation wave length and 450 nm emission wave length. The average recoveries of the method ranged from 95.3-100.7% with the relative standard deviation of 2.32-9.24%. The method is simple, accurate and has good repeatability. The results of the determination of seventeen kinds of free amino acids in burley leaves were produced by the way of different ratios of cake fertilizer and inorganic fertilizer. The results show that Aspartic acid has the highest content however ratio of cake fertilizer and inorganic fertilizer. The contents of most of the free amino acids are increased and then gradually decreased with the increase in organic manure. The contents of most of the free amino acids are very close at 15:85% ratio and 30:70% ratio of cake fertilizer and inorganic fertilizer. The total amount of free amino acids is the highest at 30:70% ratio of cake fertilizer and inorganic fertilizer. Considering comprehensively, the quality of burley leaves is the best at 30:70% ratio of cake fertilizer and inorganic fertilizer. PMID- 26858569 TI - Improvement of efficient in vitro regeneration potential of mature callus induced from Malaysian upland rice seed (Oryza sativa cv. Panderas). AB - A new and rapid protocol for optimum callus production and complete plant regeneration has been assessed in Malaysian upland rice (Oryza sativa) cv. Panderas. The effect of plant growth regulator (PGR) on the regeneration frequency of Malaysian upland rice (cv. Panderas) was investigated. Mature seeds were used as a starting material for callus induction experiment using various concentrations of 2,4-D and NAA. Optimal callus induction frequency at 90% was obtained on MS media containing 2,4-D (3 mg L(-1)) and NAA (2 mg L(-1)) after 6 weeks while no significant difference was seen on tryptophan and glutamine parameters. Embryogenic callus was recorded as compact, globular and light yellowish in color. The embryogenic callus morphology was further confirmed with scanning electron microscopy (SEM) analysis. For regeneration, induced calli were treated with various concentrations of Kin (0.5-1.5 mg L(-1)), BAP, NAA and 0.5 mg L(-1) of TDZ. The result showed that the maximum regeneration frequency (100%) was achieved on MS medium containing BAP (0.5 mg L(-1)), Kin (1.5 mg L(-1)), NAA (0.5 mg L(-1)) and TDZ (0.5 mg L(-1)) within four weeks. Developed shoots were successfully rooted on half strength MS free hormone medium and later transferred into a pot containing soil for acclimatization. This cutting-edge finding is unique over the other existing publishable data due to the good regeneration response by producing a large number of shoots. PMID- 26858570 TI - Research of population with impulsive perturbations based on dynamics of a neutral delay equation and ecological quality system. AB - This paper studies the global behaviors of a nonlinear autonomous neutral delay differential population model with impulsive perturbation. This model may be suitable for describing the dynamics of population with long larval and short adult phases. It is shown that the system may have global stability of the extinction and positive equilibria, or grow without being bounded under some conditions. PMID- 26858571 TI - Microbial contamination of vegetable crop and soil profile in arid regions under controlled application of domestic wastewater. AB - Increasing lack of potable water in arid countries leads to the use of treated wastewater for crop production. However, the use of inappropriate irrigation practices could result in a serious contamination risk to plants, soils, and groundwater with sewage water. This research was initiated in view to the increasing danger of vegetable crops and groundwater contamination with pathogenic bacteria due to wastewater land application. The research was designed to study: (1) the effect of treated wastewater irrigation on the yield and microbial contamination of the radish plant under field conditions; (2) contamination of the agricultural soil profile with fecal coliform bacteria. Effluent from a domestic wastewater treatment plant (100%) in Jeddah city, Saudi Arabia, was diluted to 80% and 40% with the groundwater of the experimental site constituting three different water qualities plus groundwater as control. Radish plant was grown in two consecutive seasons under two drip irrigation systems and four irrigation water qualities. Upon harvesting, plant weight per ha, total bacterial, fecal coliform, fecal streptococci were detected per 100 g of dry matter and compared with the control. The soil profile was also sampled at an equal distance of 3 cm from soil surface for fecal coliform detection. The results indicated that the yield increased significantly under the subsurface irrigation system and the control water quality compared to surface irrigation system and other water qualities. There was a considerable drop in the count of all bacteria species under the subsurface irrigation system compared to surface irrigation. The bacterial count/g of the plant shoot system increased as the percentage of wastewater in the irrigation water increased. Most of the fecal coliform bacteria were deposited in the first few centimeters below the column inlet and the profile exponentially decreased with increasing depth. PMID- 26858572 TI - Measurement of filter paper activities of cellulase with microplate-based assay. AB - It is always a challenge to determine the total cellulase activity efficiently without reducing accuracy. The most common total cellulase activity assay is the filter paper assay (FPA) established by the International Union of Pure and Applied Chemistry (IUPAC). A new procedure to measure the FPA with microplate based assay was studied in this work, which followed the main idea of IUPAC to dilute cellulase preparation to get fixed glucose release. FPAs of six cellulase preparations were determined with the microplate-based assay. It is shown that FPAs of cellulase Youtell, RCconc, R-10, Lerkam, Yishui and Sinopharm were 67.9, 46.0, 46.1, 27.4, 7.6 and 8.0 IU/ml respectively. There was no significant difference at the 95% confidence level between the FPA determined with IUPAC and the microplate-based assay. It could be concluded that the FPA could be determined by the microplate-based assay with the same accuracy and much more efficiency compared with that by IUPAC. PMID- 26858573 TI - The optimization of Marasmius androsaceus submerged fermentation conditions in five-liter fermentor. AB - Using desirability function, four indexes including mycelium dry weight, intracellular polysaccharide, adenosine and mannitol yield were uniformed into one expected value (Da) which further served as the assessment criteria. In our present study, Plackett-Burman design was applied to evaluate the effects of eight variables including initial pH, rotating speed, culture temperature, inoculum size, ventilation volume, culture time, inoculum age and loading volume on Da value during Marasmius androsaceus submerged fermentation via a five-liter fermentor. Culture time, initial pH and rotating speed were found to influence Da value significantly and were further optimized by Box-Behnken design. Results obtained from Box-Behnken design were analyzed by both response surface regression (Design-Expert.V8.0.6.1 software) and artificial neural network combining the genetic algorithm method (Matlab2012a software). After comparison, the optimum M. androsaceus submerged fermentation conditions via a five-liter fermentor were obtained as follows: initial pH of 6.14, rotating speed of 289.3 rpm, culture time of 6.285 days, culture temperature of 26 degrees C, inoculum size of 5%, ventilation volume of 200 L/h, inoculum age of 4 days, and loading volume of 3.5 L/5 L. The predicted Da value of the optimum model was 0.4884 and the average experimental Da value was 0.4760. The model possesses well fitness and predictive ability. PMID- 26858575 TI - Influence of season on daytime behavioral activities of donkeys in the Northern Guinea Savanna zone of Nigeria. AB - The present experiment was performed with the aim of investigating the effect of season on behavioral activities of donkeys during the rainy and harmattan seasons in the Northern Guinea zone of Nigeria. Sixteen apparently healthy donkeys were used as subjects and divided into four groups based on age. During each season, behavioral activities of each donkey were evaluated for three weeks using the focal animal sampling technique. The dry-bulb temperature (DBT), relative humidity (RH), and temperature-humidity index (THI) were obtained three times each day during the experimental period using standard procedures. In the rainy season, the mean DBT (31.65 +/- 0.49 degrees C), RH (73.63 +/- 1.09%), and THI (84.39 +/- 0.71) were significantly (P<0.0001) higher than the corresponding values of 24.00 +/- 0.44 degrees C, 36.80 +/- 0.92%, and 64.80 +/- 0.62 in the harmattan season. During the rainy season, the donkeys spent 60.00 +/- 0.77%, 25.40 +/- 0.69%, and 2.94 +/- 0.21% on grazing, resting, and grooming, respectively. During the harmattan season, the donkeys spent the most time on grazing (76.76 +/- 0.43%), less time on resting (11.97 +/- 0.38%), and the least time on grooming (0.89 +/- 0.05%). In conclusion, season and seasonal variations affect the daytime behavioral activities of donkeys in the zone, and this should be considered in husbandry practices for donkeys. PMID- 26858574 TI - A study of the distribution of color Doppler flows in the superficial digital flexor tendon of young Thoroughbreds during their training periods. AB - Aim of this study was to evaluate the relationships of exercise and tendon injury with Doppler flows appearing in the superficial digital flexor tendon (SDFT) of young Thoroughbreds during training periods. The forelimb SDFTs of 24 one- to two year-old Thoroughbreds clinically free of any orthopaedic disorders were evaluated using grey-scale (GS) and color Doppler (CD) images during two training periods between December 2013 to April 2015. Twelve horses per year were examined in December, February, and April in training periods that began in September and ended in April. The SDFT was evaluated in 3 longitudinal images of equal lengths (labelled 1, 2, 3 in order from proximal to distal), and 6 transversal images separated by equal lengths (labelled 1A, 1B, 2A, 2B, 3A and 3B in order from proximal to distal) of the metacarpus using both GS and CD. The running (canter and gallop) distance for 1 month before the date of the ultrasonographic examinations was increased in December, February, and April in both of the two training periods. CD flows defined as rhythmically blinking or pulsatory colored signals were found in 56 of 864 (6.4%) transversal CD images, in 28, 12, 13, and 3 images of 1A, 1B, 2A and 2B, respectively, and in 7, 14, and 35 images captured in December, February, and April, respectively. There were no longitudinal or transversal GS images indicating injury in the SDFTs in either of the two training periods. The increase of CD flows in the proximal regions of the SDFT are possibly related to the increase of the running distance during the training periods of the one- to two-year-old Thoroughbreds. Because no injury was diagnosed in the SDFTs by GS images during the training periods, the increase of CD flows in the proximal parts of SDFT is not necessarily predictive of tendon injury in the near future during the training period of young Thoroughbreds. PMID- 26858577 TI - Pituitary pars intermedia dysfunction (equine Cushing's disease) in a Thoroughbred stallion: a single report. AB - Equine pituitary pars intermedia dysfunction (PPID) generally occurs in older horses showing hirsutism, delayed molting, weight loss, polydipsia, polyuria, laminitis, and reproductive disorders (in broodmares), but there have been no reports on stallions. This report presents a case of a 21-year-old Thoroughbred stallion that developed hirsutism and experienced delayed molting. There were no abnormal findings for semen quality or the stallion's sexual desire. The horse was diagnosed with PPID based on dexamethasone suppression test and plasma levels of adrenocorticotropic hormone. It was then medicated with pergolide mesylate. Since the horse died due to humerus fracture, an autopsy was conducted, and pituitary adenoma was confirmed. No pathological findings were defined in the testicles; therefore, reproductive activity might not have been impaired. PMID- 26858578 TI - A clinical case of equine fungal placentitis with reference to hormone profiles and ultrasonography. AB - Fungal placentitis is an infectious disease inducing abortion in pregnant mares. In the present report, we describe a field case of abortion caused by fungal placentitis with consecutive examinations. The progesterone level and combined thickness of the uterus and placenta (CTUP) were abnormal before the onset of clinical signs. Additionally, the estradiol level started to change before the appearance of clinical signs. Abnormal serum amyloid A values and an abnormal fetal heart rate were observed after the onset of clinical signs. The present report demonstrates that the progesterone level and CTUP may be adequate as early diagnostic markers of fungal placentitis and bacterial infection. Endocrinological evaluation based on cutoff values or serial measurements were also useful for early diagnosis. PMID- 26858576 TI - Different effects of an extended photoperiod treatment on growth, gonadal function, and condition of hair coats in Thoroughbred yearlings reared under different climate conditions. AB - One- to two-year-old Thoroughbred colts and fillies being reared in Miyazaki (warm climate) and Hidaka (cold climate), Japan, were administered extended photoperiod (EP) treatment between December 20 and the following April 10, and its effect on growth, endocrine changes, gonadal activation, and hair coat condition was investigated. In colts reared in Miyazaki, no effect of EP treatment was noted on the growth indices, including body weight (BW), height at withers (HW), girth, and cannon circumference (CC), whereas the BWs and CCs of fillies were significantly higher in the EP treatment group than the control. In Hidaka, the BWs and HWs of colts and HWs of fillies were significantly higher in the EP treatment group. Gonadal activation characterized by an increase in circulating hormone concentrations was earlier in the EP treatment group for fillies reared in Miyazaki [luteinizing hormone (LH), follicle-stimulating hormone (FSH), progesterone (P4), and estradiol-17beta (E2)] and in colts (LH, testosterone, and E2) and fillies (LH, FSH, P4, and E2) reared in Hidaka. Regardless of sex and climate, prolactin was significantly higher in the EP treatment group, whereas insulin-like growth factor (IGF-I) was not. Initial ovulation occurred before April in more of the EP treatment group than the control regardless of the climate. Molting of the hair coat, examined in March, was advanced in the EP treatment group regardless of sex and climate. These results suggest that EP treatment may promote growth and gonadal activation in fillies reared in Miyazaki and in colts and fillies reared in Hidaka and that the effect may be mediated by prolactin. PMID- 26858579 TI - Seasonal changes in serum progesterone levels in Thoroughbred racehorses in training. AB - The objective of the present study was to verify the seasonal luteal activity of racehorses in training in Japan from March to August. We allocated 102 horses into a luteal activity group and non-luteal activity group. The luteal activity group included horses with serum progesterone levels that were consistently >1 ng/ml and changed by +/- 1 ng/ml. In contrast, the progesterone levels of the non luteal activity group were consistently <1 ng/ml. In late spring (from May 1 to June 30) and summer (from July 1 to August 31), the percentage of horses in the luteal activity group was significantly higher than in early spring (from March 1 to April 30, P<0.01). These findings demonstrate clear seasonal variations in ovarian activity. The present study also suggest that training for a race may not affect ovarian activity in female racehorses. PMID- 26858580 TI - Quantification of horse plasma proteins altered by xylazine using the fluorogenic derivatization-liquid chromatography-tandem mass spectrometry. AB - In the doping tests currently used in horse racing, prohibited substances or their metabolites are usually directly detected in urine or blood samples. However, despite their lasting pharmaceutical effects, some prohibited substances are rapidly eliminated from horse urine and blood, making them difficult to detect. Therefore, new indirect biomarkers for doping, such as plasma proteins that are increased by the prohibited substances, have recently attracted much attention. Here, a fluorogenic derivatization-liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) method was adopted for horse plasma proteomics analysis, in order to identify plasma proteins whose concentrations were altered in response to xylazine in Thoroughbred horses. Xylazine, which is rapidly absorbed and eliminated and has possibility of the change in the levels of plasma proteins, was selected as a model drug. Of the ten plasma proteins identified, four proteins, including three acute phase proteins (haptoglobin, ceruloplasmin, and alpha-2-macroglobulin-like), were significantly increased after xylazine administration. Therefore, our present approach might be useful in identifying indirect biomarkers of drug administration. PMID- 26858581 TI - Promoting effects of an extended photoperiod treatment on the condition of hair coats and gonadal function in Thoroughbred weanlings. AB - The effects of an extended photoperiod (EP) treatment (14.5 hr light, 9.5 hr dark) on Thoroughbred colts and fillies from December 25 at 7-9 months old to the following May at 12-14 months old on coat condition and gonadal functions were investigated. Coat condition was evaluated in April. The colts and fillies in the EP treatment group changed from winter to summer coats (molting of winter coats), whereas those in the control group did not. To determine the day of first ovulation, the plasma concentrations of progesterone were measured once a month in fillies. The day of first ovulation was advanced in the EP treatment fillies compared with the control fillies. The present study clearly demonstrated that the EP treatment advanced the molting of winter coats and advanced ovulation in fillies, even in weanlings. PMID- 26858582 TI - Effects of a nurse-led medication self-management programme in cancer patients: protocol for a mixed-method randomised controlled trial. AB - BACKGROUND: With the widespread use of orally administered anticancer agents, self-management by cancer patients is inevitable, and adherence to medication is becoming the centre of interest in oncology. METHODS/DESIGN: This mixed-method study is a two-phased approach with a combined quantitative and qualitative design. In the first phase, we will conduct a prospective randomised controlled study to assess the effects of a nurse-led medication self-management programme for patients receiving oral anticancer treatment. Patients with metastatic breast cancer, who have been newly prescribed an oral chemotherapy or a targeted therapy agent will be enrolled in the study. The participants will be randomly assigned to either the medication self-management support programme group (intervention group) or the conventional care group (control group). This will be an open-label study; therefore, neither the patients nor the nurses will be blinded. Nurses will provide patients in the intervention group with information by using the teach-back method, help patients set a goal based on their preferences, and solve problems through follow-up counselling. The primary outcome measure is adherence to medication, to be measured on the basis of the medication possession ratio (MPR), which is the ratio of the number of days of medication supply to the total days at a specified time interval. We hypothesize that the intervention group will have an MPR of >=90 % that is significantly higher than that of the control group. Secondary outcome measures include self-efficacy, quality of life, psychological distress, severity and interference of symptoms, patient satisfaction, emergency department visits, and hospital admissions. In the second phase, we will conduct focus-group interviews with intervention nurses, and perform a content analysis to understand their role and challenges these nurses will face in the programme while improving patients' medication adherence. DISCUSSION: The present study will be the first Japanese study to evaluate the effects of medication self-management support provided by nurses to patients with metastatic breast cancer who are receiving oral anticancer treatment. The study is characterised by a unique patient-centred approach aiming to help patients manage their medication based on their needs and preferences, with both quantitative and qualitative evaluations. The findings will contribute to the facilitation of medication management in cancer patients. TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR), Japan, UMIN000016597. (27 February 2015). PMID- 26858583 TI - Comparing the ability of molecular diagnosis and CAP-inhibition in identifying the really causative venom in patients with positive tests to Vespula and Polistes species. AB - BACKGROUND: Cross-reactivity among Hymenoptera venoms is an important issue when prescribing venom immunotherapy (VIT). Using all venoms eliciting a positive response results in treatment excess and unjustified cost increase. The first in vitro method that helped to identify the really causative venom was RAST inhibition, but in latest years also molecular allergy (MA) diagnostics, that detects specific sIgE to single venom allergens, was introduced. We compared the two methods in patients with double sensitization to Vespula spp. and Polistes spp. METHODS: Fifty-four patients with anaphylactic reactions to Hymenoptera stings and positive results to skin tests and sIgE measurement with whole venom from Vespula spp. and Polistes dominula were included in the study. Sera from all patients were analyzed by CAP-inhibition (Thermo Fisher Scientific, Uppsala, Sweden) and MA diagnostics with recombinant Ves v 1, Ves v 5 and Pol d 5. RESULTS: By the data obtained from MA technique, VIT would have been prescribed to 7 patients for Polistes, to 6 for Vespula, and to 41 for both venoms. With the data from CAP inhibition, it would have been a prescription to 15 patients for Polistes, to 28 for Vespula, and to 11 for both venoms. A good concordance between the results of MA and CAP-inhibition was found only when the value in kU/l of Ves v 5 were about twice those of Pol d 5, and vice versa. CONCLUSIONS: These findings suggest that in the choice of the venom to be used for VIT CAP inhibition remains a pivotal tool, because the significance of in vitro inhibition is definite and provides a diagnostic importance higher than MA in patients with positive tests to both Vespula and Polistes spp. PMID- 26858584 TI - Venous thromboembolism and persistent pulmonary hypertension in cancer patients: a cross-sectional study. AB - BACKGROUND: Cancer patients are at increased risk for venous thromboembolism (VTE). OBJECTIVE: This monocenter cross-sectional study prospectively assessed the association between a history of >=1 VTE episode and the presence of pulmonary hypertension (PH) among cancer patients presenting with pulmonary or cardiac symptoms. METHODS: A consecutive series of 583 patients underwent a diagnostic work-up for heart and lung disease. PH was diagnosed if a patient's peak systolic pressure gradient across the tricuspid valve was >=35 mmHg, as measured by echocardiography. Using multiple logistic regression analysis, the association between VTE and PH was assessed, following adjustments for age, the presence of severe airway obstruction, atrial fibrillation and left heart diseases. RESULTS: The prevalence values for PH (n = 90) and a history of VTE (n = 72) were 15.4 and 12.3 %, respectively. The median time interval between the first VTE episode and referral was 43 months. The odds of PH was higher in the subgroup with VTE (19/72; 26.4 %) than that without VTE (71/511; 13.9 %) in the unadjusted analysis [odds ratio (OR) 2.2, 95 % confidence interval (CI) 1.2, 4.0] and the adjusted model [OR 2.4, 95 % CI 1.2, 4.5]. The risk of PH did not depend on the time interval between VTE and referral. Older age and the presence of severe airway obstruction, atrial fibrillation, and left heart diseases were also associated with an increased odds of PH. CONCLUSION: In cancer patients presenting with cardiac or pulmonary symptoms, previous VTE is associated with an increased risk of persistent PH. PMID- 26858586 TI - Assessing Neurocognition via Gamified Experimental Logic: A Novel Approach to Simultaneous Acquisition of Multiple ERPs. AB - The present study describes the development of a neurocognitive paradigm: "Assessing Neurocognition via Gamified Experimental Logic" (ANGEL), for performing the parametric evaluation of multiple neurocognitive functions simultaneously. ANGEL employs an audiovisual sensory motor design for the acquisition of multiple event related potentials (ERPs)-the C1, P50, MMN, N1, N170, P2, N2pc, LRP, P300, and ERN. The ANGEL paradigm allows assessment of 10 neurocognitive variables over the course of three "game" levels of increasing complexity ranging from simple passive observation to complex discrimination and response in the presence of multiple distractors. The paradigm allows assessment of several levels of rapid decision making: speeded up response vs. response inhibition; responses to easy vs. difficult tasks; responses based on gestalt perception of clear vs. ambiguous stimuli; and finally, responses with set shifting during challenging tasks. The paradigm has been tested using 18 healthy participants from both sexes and the possibilities of varied data analyses have been presented in this paper. The ANGEL approach provides an ecologically valid assessment (as compared to existing tools) that quickly yields a very rich dataset and helps to assess multiple ERPs that can be studied extensively to assess cognitive functions in health and disease conditions. PMID- 26858585 TI - Human Bisphenol A Exposure and the "Diabesity Phenotype". AB - Bisphenol A (BPA), a known endocrine disruptor, is a food contaminant suspected of being a contributing factor to the present-day increase in obesity, diabetes, and cardiovascular disease. This issue is of increasing interest in the field of diabetes research and has become a matter of concern for regulatory agencies and food industries. Recently, the number of studies involving BPA has increased exponentially, but there are still many gaps in the knowledge of the relationship between actual BPA exposure and cardiometabolic risk and of the modalities of food intake exposure, all of which prevents sound judgments concerning the risks to human health. This review focuses on the association between human exposure to BPA and obesity, thyroid function, diabetes, insulin resistance, metabolic syndrome, cardiovascular diseases, and BPA content in food. Many cross-sectional studies support, sometimes contradictorily, an adverse effect of BPA exposure on obesity, diabetes, and cardiovascular diseases. Few prospective studies support an adverse effect of BPA exposure on such pathologies. Moreover, no intervention studies have been conducted to evaluate the causality of such associations. This is mainly due to lack of an appropriate database of BPA content in foods, thus hindering any estimation of the usual dietary BPA intake. PMID- 26858587 TI - A Proposal for a Rat Model of Spinal Cord Injury Featuring the Rubrospinal Tract and its Contributions to Locomotion and Skilled Hand Movement. AB - Spinal cord injury and repair is a dynamic field of research. The development of reliable animal models of traumatic spinal cord injury has been invaluable in providing a wealth of information regarding the pathological consequences and recovery potential of this condition. A number of injury models have been instrumental in the elaboration and the validation of therapeutic interventions aimed at reversing this once thought permanent condition. In general, the study of spinal cord injury and repair is made difficult by both its anatomical complexity and the complexity of the behavior it mediates. In this perspective paper, we suggest a new model for spinal cord investigation that simplifies problems related to both the functional and anatomical complexity of the spinal cord. We begin by reviewing and contrasting some of the most common animal models used for investigating spinal cord dysfunction. We then consider two widely used models of spinal deficit-recovery, one involving the corticospinal tracts (CTS) and the other the rubrospinal tract (RST). We argue that the simplicity of the function of the RST makes it a useful model for studying the cord and its functional repair. We also reflect on two obstacles that have hindered progress in the pre-clinical field, delaying translation to the clinical setup. The first is recovery of function without reconnection of the transected descending fibers and the second is the use of behavioral paradigms that are not under the control of the descending fiber pathway under scrutiny. PMID- 26858588 TI - Application of an Amyloid Beta Oligomer Standard in the sFIDA Assay. AB - Still, there is need for significant improvements in reliable and accurate diagnosis for Alzheimer's disease (AD) at early stages. It is widely accepted that changes in the concentration and conformation of amyloid-beta (Abeta) appear several years before the onset of first symptoms of cognitive impairment in AD patients. Because Abeta oligomers are possibly the major toxic species in AD, they are a promising biomarker candidate for the early diagnosis of the disease. To date, a variety of oligomer-specific assays have been developed, many of them ELISAs. Here, we demonstrate the sFIDA assay, a technology highly specific for Abeta oligomers developed toward single particle sensitivity. By spiking stabilized Abeta oligomers to buffer and to body fluids from control donors, we show that the sFIDA readout correlates with the applied concentration of stabilized oligomers diluted in buffer, cerebrospinal fluid (CSF), and blood plasma over several orders of magnitude. The lower limit of detection was calculated to be 22 fM of stabilized oligomers diluted in PBS, 18 fM in CSF, and 14 fM in blood plasma. PMID- 26858589 TI - Rhythm Facilitates the Detection of Repeating Sound Patterns. AB - This study investigates the influence of temporal regularity on human listeners' ability to detect a repeating noise pattern embedded in statistically identical non-repeating noise. Human listeners were presented with white noise stimuli that either contained a frozen segment of noise that repeated in a temporally regular or irregular manner, or did not contain any repetition at all. Subjects were instructed to respond as soon as they detected any repetition in the stimulus. Pattern detection performance was best when repeated targets occurred in a temporally regular manner, suggesting that temporal regularity plays a facilitative role in pattern detection. A modulation filterbank model could account for these results. PMID- 26858590 TI - Human Motor Cortex Functional Changes in Acute Stroke: Gender Effects. AB - The acute phase of stroke is accompanied by functional changes in the activity and interplay of both hemispheres. In healthy subjects, gender is known to impact the functional brain organization. We investigated whether gender influences also acute stroke functional changes. In thirty-five ischemic stroke patients, we evaluated the excitability of the affected (AH) and unaffected hemisphere (UH) by measuring resting and active motor threshold (AMT) and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation (iTBS) of AH. We also computed an index of the excitability balance between the hemispheres, laterality indexes (LI), to evidence hemispheric asymmetry. AMT differed significantly between AH and UH only in the male group (p = 0.004), not in females (p > 0.200), and both LIAMT and LIRMT were significantly higher in males than in females (respectively p = 0.033 and p = 0.042). LTP-like activity induced by iTBS in AH was more frequent in females. Gender influences the functional excitability changes that take place after human stroke and the level of LTP that can be induced by repetitive stimulation. This knowledge is of high value in the attempt of individualizing to different genders any non invasive stimulation strategy designed to foster stroke recovery. PMID- 26858591 TI - Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates. AB - Accumulation of alpha-synuclein (alpha-syn) in Lewy bodies and neurites of midbrain dopamine neurons is diagnostic for Parkinson's disease (PD), leading to the proposal that PD is a toxic gain-of-function synucleinopathy. Here we discuss the alternative viewpoint that alpha-syn displacement from synapses by misfolding and aggregation results in a toxic loss-of-function. In support of this hypothesis we provide evidence from our pilot study demonstrating that knockdown of endogenous alpha-syn in dopamine neurons of non-human primates reproduces the pattern of nigrostriatal degeneration characteristic of PD. PMID- 26858592 TI - A Parcellation Based Nonparametric Algorithm for Independent Component Analysis with Application to fMRI Data. AB - Independent Component analysis (ICA) is a widely used technique for separating signals that have been mixed together. In this manuscript, we propose a novel ICA algorithm using density estimation and maximum likelihood, where the densities of the signals are estimated via p-spline based histogram smoothing and the mixing matrix is simultaneously estimated using an optimization algorithm. The algorithm is exceedingly simple, easy to implement and blind to the underlying distributions of the source signals. To relax the identically distributed assumption in the density function, a modified algorithm is proposed to allow for different density functions on different regions. The performance of the proposed algorithm is evaluated in different simulation settings. For illustration, the algorithm is applied to a research investigation with a large collection of resting state fMRI datasets. The results show that the algorithm successfully recovers the established brain networks. PMID- 26858593 TI - Identification of Vulnerable Cell Types in Major Brain Disorders Using Single Cell Transcriptomes and Expression Weighted Cell Type Enrichment. AB - The cell types that trigger the primary pathology in many brain diseases remain largely unknown. One route to understanding the primary pathological cell type for a particular disease is to identify the cells expressing susceptibility genes. Although this is straightforward for monogenic conditions where the causative mutation may alter expression of a cell type specific marker, methods are required for the common polygenic disorders. We developed the Expression Weighted Cell Type Enrichment (EWCE) method that uses single cell transcriptomes to generate the probability distribution associated with a gene list having an average level of expression within a cell type. Following validation, we applied EWCE to human genetic data from cases of epilepsy, Schizophrenia, Autism, Intellectual Disability, Alzheimer's disease, Multiple Sclerosis and anxiety disorders. Genetic susceptibility primarily affected microglia in Alzheimer's and Multiple Sclerosis; was shared between interneurons and pyramidal neurons in Autism and Schizophrenia; while intellectual disabilities and epilepsy were attributable to a range of cell-types, with the strongest enrichment in interneurons. We hypothesized that the primary cell type pathology could trigger secondary changes in other cell types and these could be detected by applying EWCE to transcriptome data from diseased tissue. In Autism, Schizophrenia and Alzheimer's disease we find evidence of pathological changes in all of the major brain cell types. These findings give novel insight into the cellular origins and progression in common brain disorders. The methods can be applied to any tissue and disorder and have applications in validating mouse models. PMID- 26858594 TI - Oxytocin and Vasopressin Receptor Gene Polymorphisms: Role in Social and Psychiatric Traits. AB - Oxytocin (OXT) and arginine-vasopressin (AVP) are two phylogenetically conserved neuropeptides that have been implicated in a wide range of social behaviors. Although a large body of research, ranging from rodents to humans, has reported on the effects of OXT and AVP administration on affiliative and trust behaviors, and has highlighted the genetic contributions of OXT and AVP receptor polymorphisms to both social behaviors and to diseases related to social deficits, the consequences of peptide administration on psychiatric symptoms, and the impact of receptor polymorphisms on receptor function, are still unclear. Despite the exciting advances that these reports have brought to social neuroscience, they remain preliminary and suffer from the problems that are inherent to monogenetic linkage and association studies. As an alternative, some studies are using polygenic approaches, and consider the contributions of other genes and pathways, including those involving DA, 5-HT, and reelin, in addition to OXT and AVP; a handful of report are also using genome-wide association studies. This review summarizes findings on the associations between OXT and AVP receptor polymorphism, social behavior, and psychiatric diseases. In addition, we discuss reports on the interactions of OXT and AVP receptor genes and genes involved in other pathways (such as those of dopamine, serotonin, and reelin), as well as research that has shed some light on the impact of gene polymorphisms on the volume, connectivity, and activation of specific neural structures, differential receptor expression, and plasma levels of the OXT and AVP peptides. We hope that this effort will be helpful for understanding the studies performed so far, and for encouraging the inclusion of other candidate genes not explored to date. PMID- 26858596 TI - Electrophysiological Evidence for a Direct Link between the Main and Accessory Olfactory Bulbs in the Adult Rat. AB - It is accepted that the main- and accessory- olfactory systems exhibit overlapping responses to pheromones and odorants. We performed whole-cell patch clamp recordings in adult rat olfactory bulb slices to define a possible interaction between the first central relay of these systems: the accessory olfactory bulb (AOB) and the main olfactory bulb (MOB). This was tested by applying electrical field stimulation in the dorsal part of the MOB while recording large principal cells (LPCs) of the anterior AOB (aAOB). Additional recordings of LPCs were performed at either side of the plane of intersection between the aAOB and posterior-AOB (pAOB) halves, or linea alba, while applying field stimulation to the opposite half. A total of 92 recorded neurons were filled during whole-cell recordings with biocytin and studied at the light microscope. Neurons located in the aAOB (n = 6, 8%) send axon collaterals to the MOB since they were antidromically activated in the presence of glutamate receptor antagonists (APV and CNQX). Recorded LPCs evoked orthodromic excitatory post-synaptic responses (n = 6, aAOB; n = 1, pAOB) or antidromic action potentials (n = 8, aAOB; n = 7, pAOB) when applying field stimulation to the opposite half of the recording site (e.g., recording in aAOB; stimulating in pAOB, and vice-versa). Observation of the filled neurons revealed that indeed, LPCs send axon branches that cross the linea alba to resolve in the internal cellular layer. Additionally, LPCs of the aAOB send axon collaterals to dorsal MOB territory. Notably, while performing AOB recordings we found a sub-population of neurons (24% of the total) that exhibited voltage-dependent bursts of action potentials. Our findings support the existence of: 1. a direct projection from aAOB LPCs to dorsal-MOB, 2. physiologically active synapses linking aAOB and pAOB, and 3. pacemaker-like neurons in both AOB halves. This work was presented in the form of an Abstract on SfN 2014 (719.14/EE17). PMID- 26858595 TI - Functional Imaging of Autonomic Regulation: Methods and Key Findings. AB - Central nervous system processing of autonomic function involves a network of regions throughout the brain which can be visualized and measured with neuroimaging techniques, notably functional magnetic resonance imaging (fMRI). The development of fMRI procedures has both confirmed and extended earlier findings from animal models, and human stroke and lesion studies. Assessments with fMRI can elucidate interactions between different central sites in regulating normal autonomic patterning, and demonstrate how disturbed systems can interact to produce aberrant regulation during autonomic challenges. Understanding autonomic dysfunction in various illnesses reveals mechanisms that potentially lead to interventions in the impairments. The objectives here are to: (1) describe the fMRI neuroimaging methodology for assessment of autonomic neural control, (2) outline the widespread, lateralized distribution of function in autonomic sites in the normal brain which includes structures from the neocortex through the medulla and cerebellum, (3) illustrate the importance of the time course of neural changes when coordinating responses, and how those patterns are impacted in conditions of sleep-disordered breathing, and (4) highlight opportunities for future research studies with emerging methodologies. Methodological considerations specific to autonomic testing include timing of challenges relative to the underlying fMRI signal, spatial resolution sufficient to identify autonomic brainstem nuclei, blood pressure, and blood oxygenation influences on the fMRI signal, and the sustained timing, often measured in minutes of challenge periods and recovery. Key findings include the lateralized nature of autonomic organization, which is reminiscent of asymmetric motor, sensory, and language pathways. Testing brain function during autonomic challenges demonstrate closely-integrated timing of responses in connected brain areas during autonomic challenges, and the involvement with brain regions mediating postural and motoric actions, including respiration, and cardiac output. The study of pathological processes associated with autonomic disruption shows susceptibilities of different brain structures to altered timing of neural function, notably in sleep disordered breathing, such as obstructive sleep apnea and congenital central hypoventilation syndrome. The cerebellum, in particular, serves coordination roles for vestibular stimuli and blood pressure changes, and shows both injury and substantially altered timing of responses to pressor challenges in sleep-disordered breathing conditions. The insights into central autonomic processing provided by neuroimaging have assisted understanding of such regulation, and may lead to new treatment options for conditions with disrupted autonomic function. PMID- 26858597 TI - HPA Axis Gene Expression and DNA Methylation Profiles in Rats Exposed to Early Life Stress, Adult Voluntary Ethanol Drinking and Single Housing. AB - The neurobiological basis of early life stress (ELS) impact on vulnerability to alcohol use disorder is not fully understood. The effect of ELS, adult ethanol consumption and single housing, on expression of stress and DNA methylation regulatory genes as well as blood corticosterone levels was investigated in the hypothalamus and pituitary of adult out-bred Wistar rats subjected to different rearing conditions. A prolonged maternal separation (MS) of 360 min (MS360) was used to study the effect of ELS, and a short MS of 15 min (MS15) was used as a control. Voluntary ethanol drinking was assessed using a two-bottle free choice paradigm to simulate human episodic drinking. The effects of single housing and ethanol were assessed in conventional animal facility rearing (AFR) conditions. Single housing in adulthood was associated with lower Crhr1 and higher Pomc expression in the pituitary, whereas ethanol drinking was associated with higher expression of Crh in the hypothalamus and Crhr1 in the pituitary, accompanied by lower corticosterone levels. As compared to controls with similar early life handling, rats exposed to ELS displayed lower expression of Pomc in the hypothalamus, and higher Dnmt1 expression in the pituitary. Voluntary ethanol drinking resulted in lower Fkbp5 expression in the pituitary and higher Crh expression in the hypothalamus, independently of rearing conditions. In rats exposed to ELS, water and ethanol drinking was associated with higher and lower corticosterone levels, respectively. The use of conventionally reared rats as control group yielded more significant results than the use of rats exposed to short MS. Positive correlations, restricted to the hypothalamus and ELS group, were observed between the expression of the hypothalamus-pituitary-adrenal receptor and the methylation-related genes. Promoter DNA methylation and expression of respective genes did not correlate suggesting that other loci are involved in transcriptional regulation. Concluding, single housing is a confounding factor to be considered in voluntary ethanol drinking paradigms. ELS and ethanol drinking in adulthood exert independent effects on hypothalamic and pituitary related genes, however, in a manner dependent on the control group used. PMID- 26858598 TI - Analysis of Expression Pattern and Genetic Deletion of Netrin5 in the Developing Mouse. AB - Boundary cap cells (BCC) are a transient, neural-crest-derived population found at the motor exit point (MEP) and dorsal root entry zone (DREZ) of the embryonic spinal cord. These cells contribute to the central/peripheral nervous system (CNS/PNS) boundary, and in their absence neurons and glia from the CNS migrate into the PNS. We found Netrin5 (Ntn5), a previously unstudied member of the netrin gene family, to be robustly expressed in BCC. We generated Ntn5 knockout mice and examined neurodevelopmental and BCC-related phenotypes. No abnormalities in cranial nerve guidance, dorsal root organization, or sensory projections were found. However, Ntn5 mutant embryos did have ectopic motor neurons (MNs) that migrated out of the ventral horn and into the motor roots. Previous studies have implicated semaphorin6A (Sema6A) in BCC signaling to plexinA2 (PlxnA2)/neuropilin2 (Nrp2) in MNs in restricting MN cell bodies to the ventral horn, particularly in the caudal spinal cord. In Ntn5 mutants, ectopic MNs are likely to be a different population, as more ectopias were found rostrally. Furthermore, ectopic MNs in Ntn5 mutants were not immunoreactive for NRP2. The netrin receptor deleted in colorectal cancer (DCC) is a potential receptor for NTN5 in MNs, as similar ectopic neurons were found in Dcc mutant mice, but not in mice deficient for other netrin receptors. Thus, Ntn5 is a novel netrin family member that is expressed in BCC, functioning to prevent MN migration out of the CNS. PMID- 26858601 TI - Editorial: Neuronal Mechanics and Transport. PMID- 26858600 TI - Bicarbonate and Ca(2+) Sensing Modulators Activate Photoreceptor ROS-GC1 Synergistically. AB - Photoreceptor ROS-GC1, a prototype subfamily member of the membrane guanylate cyclase family, is a central component of phototransduction. It is a single transmembrane-spanning protein, composed of modular blocks. In rods, guanylate cyclase activating proteins (GCAPs) 1 and 2 bind to its juxtamembrane domain (JMD) and the C-terminal extension, respectively, to accelerate cyclic GMP synthesis when Ca(2+) levels are low. In cones, the additional expression of the Ca(2+)-dependent guanylate cyclase activating protein (CD-GCAP) S100B which binds to its C-terminal extension, supports acceleration of cyclic GMP synthesis at high Ca(2+) levels. Independent of Ca(2+), ROS-GC1 activity is also stimulated directly by bicarbonate binding to the core catalytic domain (CCD). Several enticing molecular features of this transduction system are revealed in the present study. In combination, bicarbonate and Ca(2+)-dependent modulators raised maximal ROS-GC activity to levels that exceeded the sum of their individual effects. The F(514)S mutation in ROS-GC1 that causes blindness in type 1 Leber's congenital amaurosis (LCA) severely reduced basal ROS-GC1 activity. GCAP2 and S100B Ca(2+) signaling modes remained functional, while the GCAP1-modulated mode was diminished. Bicarbonate nearly restored basal activity as well as GCAP2- and S100B-stimulated activities of the F(514)S mutant to normal levels but could not resurrect GCAP1 stimulation. We conclude that GCAP1 and GCAP2 forge distinct pathways through domain-specific modules of ROS-GC1 whereas the S100B and GCAP2 pathways may overlap. The synergistic interlinking of bicarbonate to GCAPs- and S100B-modulated pathways intensifies and tunes the dependence of cyclic GMP synthesis on intracellular Ca(2+). Our study challenges the recently proposed GCAP1 and GCAP2 "overlapping" phototransduction model (Peshenko et al., 2015b). PMID- 26858602 TI - GABABR-Dependent Long-Term Depression at Hippocampal Synapses between CB1 Positive Interneurons and CA1 Pyramidal Cells. AB - Activity induced long lasting modifications of synaptic efficacy have been extensively studied in excitatory synapses, however, long term plasticity is also a property of inhibitory synapses. Inhibitory neurons in the hippocampal CA1 region can be subdivided according to the compartment they target on the pyramidal cell. Some interneurons preferentially innervate the perisomatic area and axon hillock of the pyramidal cells while others preferentially target dendritic branches and spines. Another characteristic feature allowing functional classification of interneurons is cell type specific expression of different neurochemical markers and receptors. In the hippocampal CA1 region, nearly 90% of the interneurons expressing cannabinoid type 1 receptors (CB1R) also express cholecystokinin (CCK). Therefore, the functional presence of CB1 receptors can be used for identification of the inhibitory input from CCK positive (CCK+) interneurons to CA1 pyramidal cells. The goal of this study was to explore the nature of long term plasticity at the synapses between interneurons expressing CB1Rs (putative CCK+) and pyramidal neurons in the CA1 region of the hippocampus in vitro. We found that theta burst stimulation triggered robust long-term depression (LTD) at this synapse. The locus of LTD induction was postsynaptic and required activation of GABAB receptors. We also showed that LTD at this synaptic connection involves GABABR-dependent suppression of adenylyl cyclase and consequent reduction of PKA activity. In this respect, CB1+ to pyramidal cell synapses differ from the majority of the other hippocampal inhibitory connections where theta burst stimulation results in long-term potentiation. PMID- 26858599 TI - The Ubiquitin-Proteasome System: Potential Therapeutic Targets for Alzheimer's Disease and Spinal Cord Injury. AB - The ubiquitin-proteasome system (UPS) is a crucial protein degradation system in eukaryotes. Herein, we will review advances in the understanding of the role of several proteins of the UPS in Alzheimer's disease (AD) and functional recovery after spinal cord injury (SCI). The UPS consists of many factors that include E3 ubiquitin ligases, ubiquitin hydrolases, ubiquitin and ubiquitin-like molecules, and the proteasome itself. An extensive body of work links UPS dysfunction with AD pathogenesis and progression. More recently, the UPS has been shown to have vital roles in recovery of function after SCI. The ubiquitin hydrolase (Uch-L1) has been proposed to increase cellular levels of mono-ubiquitin and hence to increase rates of protein turnover by the UPS. A low Uch-L1 level has been linked with Abeta accumulation in AD and reduced neuroregeneration after SCI. One likely mechanism for these beneficial effects of Uch-L1 is reduced turnover of the PKA regulatory subunit and consequently, reduced signaling via CREB. The neuron specific F-box protein Fbx2 ubiquitinates beta-secretase thus targeting it for proteasomal degradation and reducing generation of Abeta. Both Uch-L1 and Fbx2 improve synaptic plasticity and cognitive function in mouse AD models. The role of Fbx2 after SCI has not been examined, but abolishing beta-secretase reduces neuronal recovery after SCI, associated with reduced myelination. UBB+1, which arises through a frame-shift mutation in the ubiquitin gene that adds 19 amino acids to the C-terminus of ubiquitin, inhibits proteasomal function and is associated with increased neurofibrillary tangles in patients with AD, Pick's disease and Down's syndrome. These advances in understanding of the roles of the UPS in AD and SCI raise new questions but, also, identify attractive and exciting targets for potential, future therapeutic interventions. PMID- 26858603 TI - Anticonvulsant Effect of Time-Restricted Feeding in a Pilocarpine-Induced Seizure Model: Metabolic and Epigenetic Implications. AB - A new generation of antiepileptic drugs has emerged; however, one-third of epilepsy patients do not properly respond to pharmacological treatments. The purpose of the present study was to investigate whether time-restricted feeding (TRF) has an anticonvulsant effect and whether this restrictive diet promotes changes in energy metabolism and epigenetic modifications in a pilocarpine induced seizure model. To resolve our hypothesis, one group of rats had free access to food and water ad libitum (AL) and a second group underwent a TRF schedule. We used the lithium-pilocarpine model to induce status epilepticus (SE), and behavioral seizure monitoring was analyzed. Additionally, an electroencephalography (EEG) recording was performed to verify the effect of TRF on cortical electrical activity after a pilocarpine injection. For biochemical analysis, animals were sacrificed 24 h after SE and hippocampal homogenates were used to evaluate the proteins related to metabolism and chromatin structure. Our results showed that TRF had an anticonvulsant effect as measured by the prolonged latency of forelimb clonus seizure, a decrease in the seizure severity score and fewer animals reaching SE. Additionally, the power of the late phase EEG recordings in the AL group was significantly higher than the TRF group. Moreover, we found that TRF is capable of inducing alterations in signaling pathways that regulate energy metabolism, including an increase in the phosphorylation of AMP dependent kinase (AMPK) and a decrease in the phosphorylation of Akt kinase. Furthermore, we found that TRF was able to significantly increase the beta hydroxybutyrate (beta-HB) concentration, an endogenous inhibitor of histone deacetylases (HDACs). Finally, we found a significant decrease in HDAC activity as well as an increase in acetylation on histone 3 (H3) in hippocampal homogenates from the TRF group. These findings suggest that alterations in energy metabolism and the increase in beta-HB mediated by TRF may inhibit HDAC activity, thus increasing histone acetylation and producing changes in the chromatin structure, which likely facilitates the transcription of a subset of genes that confer anticonvulsant activity. PMID- 26858604 TI - Paired Burst Stimulation Causes GABAA Receptor-Dependent Spike Firing Facilitation in CA1 of Rat Hippocampal Slices. AB - The theta oscillation (4-8 Hz) is a pivotal form of oscillatory activity in the hippocampus that is intermittently concurrent with gamma (25-100 Hz) burst events. In in vitro preparation, a stimulation protocol that mimics the theta oscillation, theta burst stimulation (TBS), is used to induce long-term potentiation. Thus, TBS is thought to have a distinct role in the neural network of the hippocampal slice preparation. However, the specific mechanisms that make TBS induce such neural circuit modifications are still unknown. Using electrophysiology and voltage-sensitive dye imaging (VSDI), we have found that TBS induces augmentation of spike firing. The augmentation was apparent in the first couple of brief burst stimulation (100 Hz four pulses) on a TBS-train in a presence of NMDA receptor blocker (APV 50 MUM). In this study, we focused on the characterizes of the NMDA independent augmentation caused by a pair of the brief burst stimulation (the first pair of the TBS; paired burst stimulation-PBS). We found that PBS enhanced membrane potential responses on VSDI signal and intracellular recordings while it was absent in the current recording under whole cell clamp condition. The enhancement of the response accompanied the augmentation of excitatory postsynaptic potential (EPSP) to spike firing (E-S) coupling. The paired burst facilitation (PBF) reached a plateau when the number of the first burst stimulation (priming burst) exceeds three. The interval between the bursts of 150 ms resulted in the maximum PBF. Gabazine (a GABAA receptor antagonist) abolished PBF. The threshold for spike generation of the postsynaptic cells measured with a current injection to cells was not lowered by the priming burst of PBS. These results indicate that PBS activates the GABAergic system to cause short-term E-S augmentation without raising postsynaptic excitability. We propose that a GABAergic system of area CA1 of the hippocampus produce the short-term E-S plasticity that could cause exaggerated spike-firing upon a theta-gamma activity distinctively, thus making the neural circuit of the CA1 act as a specific amplifier of the oscillation signal. PMID- 26858605 TI - Adducin at the Neuromuscular Junction in Amyotrophic Lateral Sclerosis: Hanging on for Dear Life. AB - The neurological dysfunction in amyotrophic lateral sclerosis (ALS)/motor neurone disease (MND) is associated with defective nerve-muscle contacts early in the disease suggesting that perturbations of cell adhesion molecules (CAMs) linking the pre- and post-synaptic components of the neuromuscular junction (NMJ) are involved. To search for candidate proteins implicated in this degenerative process, researchers have studied the Drosophila larval NMJ and find that the cytoskeleton-associated protein, adducin, is ideally placed to regulate synaptic contacts. By controlling the levels of synaptic proteins, adducin can de stabilize synaptic contacts. Interestingly, elevated levels of phosphorylated adducin have been reported in ALS patients and in a mouse model of the disease. Adducin is regulated by phosphorylation through protein kinase C (PKC), some isoforms of which exhibit Ca(2+)-dependence, raising the possibility that changes in intracellular Ca(2+) might alter PKC activation and secondarily influence adducin phosphorylation. Furthermore, adducin has interactions with the alpha subunit of the Na(+)/K(+)-ATPase. Thus, the phosphorylation of adducin may secondarily influence synaptic stability at the NMJ and so influence pre- and post-synaptic integrity at the NMJ in ALS. PMID- 26858606 TI - The Relative Contribution of NMDARs to Excitatory Postsynaptic Currents is Controlled by Ca(2+)-Induced Inactivation. AB - NMDA receptors (NMDARs) are important mediators of excitatory synaptic transmission and plasticity. A hallmark of these channels is their high permeability to Ca(2+). At the same time, they are themselves inhibited by the elevation of intracellular Ca(2+) concentration. It is unclear however, whether the Ca(2+) entry associated with single NMDAR mediated synaptic events is sufficient to self-inhibit their activation. Such auto-regulation would have important effects on the dynamics of synaptic excitation in several central neuronal networks. Therefore, we studied NMDAR-mediated synaptic currents in mouse hippocampal CA1 pyramidal neurons. Postsynaptic responses to subthreshold Schaffer collateral stimulation depended strongly on the absence or presence of intracellular Ca(2+) buffers. Loading of pyramidal cells with exogenous Ca(2+) buffers increased the amplitude and decay time of NMDAR mediated EPSCs (EPSPs) and prolonged the time window for action potential (AP) generation. Our data indicate that the Ca(2+) influx mediated by unitary synaptic events is sufficient to produce detectable self-inhibition of NMDARs even at a physiological Mg(2+) concentration. Therefore, the contribution of NMDARs to synaptic excitation is strongly controlled by both previous synaptic activity as well as by the Ca(2+) buffer capacity of postsynaptic neurons. PMID- 26858607 TI - Mild KCC2 Hypofunction Causes Inconspicuous Chloride Dysregulation that Degrades Neural Coding. AB - Disinhibition caused by Cl(-) dysregulation is implicated in several neurological disorders. This form of disinhibition, which stems primarily from impaired Cl(-) extrusion through the co-transporter KCC2, is typically identified by a depolarizing shift in GABA reversal potential (E GABA). Here we show, using computer simulations, that intracellular [Cl(-)] exhibits exaggerated fluctuations during transient Cl(-) loads and recovers more slowly to baseline when KCC2 level is even modestly reduced. Using information theory and signal detection theory, we show that increased Cl(-) lability and settling time degrade neural coding. Importantly, these deleterious effects manifest after less KCC2 reduction than needed to produce the gross changes in E GABA required for detection by most experiments, which assess KCC2 function under weak Cl(-) load conditions. By demonstrating the existence and functional consequences of "occult" Cl(-) dysregulation, these results suggest that modest KCC2 hypofunction plays a greater role in neurological disorders than previously believed. PMID- 26858608 TI - Response: Commentary: "Prdm13 regulates subtype specification of retinal amacrine interneurons and modulates visual sensitivity". PMID- 26858609 TI - Spatiotemporal Pattern of Doublecortin Expression in the Retina of the Sea Lamprey. AB - Despite the importance of doublecortin (DCX) for the development of the nervous system, its expression in the retina of most vertebrates is still unknown. The key phylogenetic position of lampreys, together with their complex life cycle, with a long blind larval stage and an active predator adult stage, makes them an interesting model to study retinal development. Here, we studied the spatiotemporal pattern of expression of DCX in the retina of the sea lamprey. In order to characterize the DCX expressing structures, the expression of acetylated alpha-tubulin (a neuronal marker) and cytokeratins (glial marker) was also analyzed. Tract-tracing methods were used to label ganglion cells. DCX immunoreactivity appeared initially in photoreceptors, ganglion cells and in fibers of the prolarval retina. In larvae smaller than 100 mm, DCX expression was observed in photoreceptors, in cells located in the inner nuclear and inner plexiform layers (IPLs) and in fibers coursing in the nuclear and IPLs, and in the optic nerve (ON). In retinas of premetamorphic and metamorphic larvae, DCX immunoreactivity was also observed in radially oriented cells and fibers and in a layer of cells located in the outer part of the inner neuroblastic layer (INbL) of the lateral retina. Photoreceptors and fibers ending in the outer limitans membrane (OLM) showed DCX expression in adults. Some retinal pigment epithelium cells were also DCX immunoreactive. Immunofluorescence for alpha-tubulin in premetamorphic larvae showed coexpression in most of the DCX immunoreactive structures. No cells/fibers were found showing DCX and cytokeratins colocalization. The perikaryon of mature ganglion cells is DCX negative. The expression of DCX in sea lamprey retinas suggests that it could play roles in the migration of cells that differentiate in the metamorphosis, in the establishment of connections of ganglion cells and in the development of photoreceptors. Our results also suggest that the radial glia and retinal pigment epithelium cells of lampreys are neurogenic. Comparison of our observations with those reported in gnathostomes reveals similarities and interesting differences probably due to the peculiar development of the sea lamprey retina. PMID- 26858610 TI - Distribution of 28 kDa Calbindin-Immunopositive Neurons in the Cat Spinal Cord. AB - The distribution of vitamin D-dependent calcium-binding protein (28 kDa calbindin) was investigated in cat lumbar and sacral spinal cord segments (L1 S3). We observed specific multi-dimensional distributions over the spinal segments for small immunopositive cells in Rexed laminae II-III and medium-to large cells of varying morphology in lamina I and laminae V-VIII. The small neurons in laminae II-III were clustered into the columns along the dorsal horn curvature. The medium-to-large cells were grouped into four assemblages that were located in (1) the most lateral region of lamina VII at the L1-L4 level; (2) the laminae IV-V boundary at the L5-L7 level; (3) the lamina VII dorsal border at the L5-L7 level; and (4) the lamina VIII at the L5-S3 level. The data obtained suggest that the morphological and physiological heterogeneity of calbindin immunolabeling cells formed morpho-functional clusters over the gray matter. A significant portion of the lumbosacral enlargement had immunopositive neurons within all Rexed laminae, suggesting an important functional role within and among the spinal networks that control hindlimb movements. PMID- 26858611 TI - White Matter Microstructure is Associated with Auditory and Tactile Processing in Children with and without Sensory Processing Disorder. AB - Sensory processing disorders (SPDs) affect up to 16% of school-aged children, and contribute to cognitive and behavioral deficits impacting affected individuals and their families. While sensory processing differences are now widely recognized in children with autism, children with sensory-based dysfunction who do not meet autism criteria based on social communication deficits remain virtually unstudied. In a previous pilot diffusion tensor imaging (DTI) study, we demonstrated that boys with SPD have altered white matter microstructure primarily affecting the posterior cerebral tracts, which subserve sensory processing and integration. This disrupted microstructural integrity, measured as reduced white matter fractional anisotropy (FA), correlated with parent report measures of atypical sensory behavior. In this present study, we investigate white matter microstructure as it relates to tactile and auditory function in depth with a larger, mixed-gender cohort of children 8-12 years of age. We continue to find robust alterations of posterior white matter microstructure in children with SPD relative to typically developing children (TDC), along with more spatially distributed alterations. We find strong correlations of FA with both parent report and direct measures of tactile and auditory processing across children, with the direct assessment measures of tactile and auditory processing showing a stronger and more continuous mapping to the underlying white matter integrity than the corresponding parent report measures. Based on these findings of microstructure as a neural correlate of sensory processing ability, diffusion MRI merits further investigation as a tool to find biomarkers for diagnosis, prognosis and treatment response in children with SPD. To our knowledge, this work is the first to demonstrate associations of directly measured tactile and non-linguistic auditory function with white matter microstructural integrity - not just in children with SPD, but also in TDC. PMID- 26858613 TI - Astrocyte-Neuron Interactions during Learning May Occur by Lactate Signaling Rather than Metabolism. PMID- 26858614 TI - Editorial: Neural Circuitry of Behavioral Flexibility: Dopamine and Related Systems. PMID- 26858612 TI - Hippocampal-Prefrontal Interactions in Cognition, Behavior and Psychiatric Disease. AB - The hippocampus and prefrontal cortex (PFC) have long been known to play a central role in various behavioral and cognitive functions. More recently, electrophysiological and functional imaging studies have begun to examine how interactions between the two structures contribute to behavior during various tasks. At the same time, it has become clear that hippocampal-prefrontal interactions are disrupted in psychiatric disease and may contribute to their pathophysiology. These impairments have most frequently been observed in schizophrenia, a disease that has long been associated with hippocampal and prefrontal dysfunction. Studies in animal models of the illness have also begun to relate disruptions in hippocampal-prefrontal interactions to the various risk factors and pathophysiological mechanisms of the illness. The goal of this review is to summarize what is known about the role of hippocampal-prefrontal interactions in normal brain function and compare how these interactions are disrupted in schizophrenia patients and animal models of the disease. Outstanding questions for future research on the role of hippocampal-prefrontal interactions in both healthy brain function and disease states are also discussed. PMID- 26858615 TI - Resignation Syndrome: Catatonia? Culture-Bound? AB - Resignation syndrome (RS) designates a long-standing disorder predominately affecting psychologically traumatized children and adolescents in the midst of a strenuous and lengthy migration process. Typically a depressive onset is followed by gradual withdrawal progressing via stupor into a state that prompts tube feeding and is characterized by failure to respond even to painful stimuli. The patient is seemingly unconscious. Recovery ensues within months to years and is claimed to be dependent on the restoration of hope to the family. Descriptions of disorders resembling RS can be found in the literature and the condition is unlikely novel. Nevertheless, the magnitude and geographical distribution stand out. Several hundred cases have been reported exclusively in Sweden in the past decade prompting the Swedish National Board of Health and Welfare to recognize RS as a separate diagnostic entity. The currently prevailing stress hypothesis fails to account for the regional distribution and contributes little to treatment. Consequently, a re-evaluation of diagnostics and treatment is required. Psychogenic catatonia is proposed to supply the best fit with the clinical presentation. Treatment response, altered brain metabolism or preserved awareness would support this hypothesis. Epidemiological data suggests culture-bound beliefs and expectations to generate and direct symptom expression and we argue that culture-bound psychogenesis can accommodate the endemic distribution. Last, we review recent models of predictive coding indicating how expectation processes are crucially involved in the placebo and nocebo effect, delusions and conversion disorders. Building on this theoretical framework we propose a neurobiological model of RS in which the impact of overwhelming negative expectations are directly causative of the down-regulation of higher order and lower order behavioral systems in particularly vulnerable individuals. PMID- 26858617 TI - Recognition of Modified Conditioning Sounds by Competitively Trained Guinea Pigs. AB - The guinea pig (GP) is an often-used species in hearing research. However, behavioral studies are rare, especially in the context of sound recognition, because of difficulties in training these animals. We examined sound recognition in a social competitive setting in order to examine whether this setting could be used as an easy model. Two starved GPs were placed in the same training arena and compelled to compete for food after hearing a conditioning sound (CS), which was a repeat of almost identical sound segments. Through a 2-week intensive training, animals were trained to demonstrate a set of distinct behaviors solely to the CS. Then, each of them was subjected to generalization tests for recognition of sounds that had been modified from the CS in spectral, fine temporal and tempo (i.e., intersegment interval, ISI) dimensions. Results showed that they discriminated between the CS and band-rejected test sounds but had no preference for a particular frequency range for the recognition. In contrast, sounds modified in the fine temporal domain were largely perceived to be in the same category as the CS, except for the test sound generated by fully reversing the CS in time. Animals also discriminated sounds played at different tempos. Test sounds with ISIs shorter than that of the multi-segment CS were discriminated from the CS, while test sounds with ISIs longer than that of the CS segments were not. For the shorter ISIs, most animals initiated apparently positive food-access behavior as they did in response to the CS, but discontinued it during the sound on period probably because of later recognition of tempo. Interestingly, the population range and mean of the delay time before animals initiated the food access behavior were very similar among different ISI test sounds. This study, for the first time, demonstrates a wide aspect of sound discrimination abilities of the GP and will provide a way to examine tempo perception mechanisms using this animal species. PMID- 26858618 TI - Effects of Mineralocorticoid Receptor Overexpression on Anxiety and Memory after Early Life Stress in Female Mice. AB - Early-life stress (ELS) is a risk factor for the development of psychopathology, particularly in women. Human studies have shown that certain haplotypes of NR3C2, encoding the mineralocorticoid receptor (MR), that result in gain of function, may protect against the consequences of stress exposure, including childhood trauma. Here, we tested the hypothesis that forebrain-specific overexpression of MR in female mice would ameliorate the effects of ELS on anxiety and memory in adulthood. We found that ELS increased anxiety, did not alter spatial discrimination and reduced contextual fear memory in adult female mice. Transgenic overexpression of MR did not alter anxiety but affected spatial memory performance and enhanced contextual fear memory formation. The effects of ELS on anxiety and contextual fear were not affected by transgenic overexpression of MR. Thus, MR overexpression in the forebrain does not represent a major resilience factor to early life adversity in female mice. PMID- 26858619 TI - Time Course of Corticospinal Excitability and Intracortical Inhibition Just before Muscle Relaxation. AB - Using transcranial magnetic stimulation (TMS), we investigated how short-interval intracortical inhibition (SICI) was involved with transient motor cortex (M1) excitability changes observed just before the transition from muscle contraction to muscle relaxation. Ten healthy participants performed a simultaneous relaxation task of the ipsilateral finger and foot, relaxing from 10% of their maximal voluntary contraction (MVC) force after the go signal. In the simple reaction time (RT) paradigm, single or paired TMS pulses were randomly delivered after the go signal, and motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous (FDI) muscle. We analyzed the time course prior to the estimated relaxation reaction time (RRT), defined here as the onset of voluntary relaxation. SICI decreased in the 80-100 ms before RRT, and MEPs were significantly greater in amplitude in the 60-80 ms period before RRT than in the other intervals in single-pulse trials. TMS pulses did not effectively increase RRT. These results show that cortical excitability in the early stage, before muscle relaxation, plays an important role in muscle relaxation control. SICI circuits may vary between decreased and increased activation to continuously maintain muscle relaxation during or after a relaxation response. With regard to M1 excitability dynamics, we suggest that SICI also dynamically changes throughout the muscle relaxation process. PMID- 26858616 TI - Modulation of Fear Extinction by Stress, Stress Hormones and Estradiol: A Review. AB - Fear acquisition and extinction are valid models for the etiology and treatment of anxiety, trauma- and stressor-related disorders. These disorders are assumed to involve aversive learning under acute and/or chronic stress. Importantly, fear conditioning and stress share common neuronal circuits. The stress response involves multiple changes interacting in a time-dependent manner: (a) the fast first-wave stress response [with central actions of noradrenaline, dopamine, serotonin, corticotropin-releasing hormone (CRH), plus increased sympathetic tone and peripheral catecholamine release] and (b) the second-wave stress response [with peripheral release of glucocorticoids (GCs) after activation of the hypothalamus-pituitary-adrenocortical (HPA) axis]. Control of fear during extinction is also sensitive to these stress-response mediators. In the present review, we will thus examine current animal and human data, addressing the role of stress and single stress-response mediators for successful acquisition, consolidation and recall of fear extinction. We report studies using pharmacological manipulations targeting a number of stress-related neurotransmitters and neuromodulators [monoamines, opioids, endocannabinoids (eCBs), neuropeptide Y, oxytocin, GCs] and behavioral stress induction. As anxiety, trauma- and stressor-related disorders are more common in women, recent research focuses on female sex hormones and identifies a potential role for estradiol in fear extinction. We will thus summarize animal and human data on the role of estradiol and explore possible interactions with stress or stress response mediators in extinction. This also aims at identifying time-windows of enhanced (or reduced) sensitivity for fear extinction, and thus also for successful exposure therapy. PMID- 26858620 TI - Altered Structural Correlates of Impulsivity in Adolescents with Internet Gaming Disorder. AB - Recent studies suggested that internet gaming disorder (IGD) was associated with impulsivity and structural abnormalities in brain gray matter (GM). However, no morphometric study has examined the association between GM and impulsivity in IGD individuals. In this study, 25 adolescents with IGD and 27 healthy controls (HCs) were recruited, and the relationship between Barratt impulsiveness scale-11 (BIS) score and gray matter volume (GMV) was investigated with the voxel-based morphometric (VBM) correlation analysis. Then, the intergroup differences in correlation between BIS score and GMV were tested across all GM voxels. Our results showed that the correlations between BIS score and GMV of the right dorsomedial prefrontal cortex (dmPFC), the bilateral insula and the orbitofrontal cortex (OFC), the right amygdala and the left fusiform gyrus decreased in the IGD group compared to the HCs. Region-of-interest (ROI) analysis revealed that GMV in all these clusters showed significant positive correlations with BIS score in the HCs, while no significant correlation was found in the IGD group. Our findings demonstrated that dysfunction of these brain areas involved in the behavior inhibition, attention and emotion regulation might contribute to impulse control problems in IGD adolescents. PMID- 26858621 TI - Effect Anticipation Affects Perceptual, Cognitive, and Motor Phases of Response Preparation: Evidence from an Event-Related Potential (ERP) Study. AB - The anticipation of action effects is a basic process that can be observed even for key-pressing responses in a stimulus-response paradigm. In Ziessler et al.'s (2012) experiments participants first learned arbitrary effects of key-pressing responses. In the test phase an imperative stimulus determined the response, but participants withheld the response until a Go-stimulus appeared. Reaction times (RTs) were shorter if the Go-stimulus was compatible with the learned response effect. This is strong evidence that effect representations were activated during response planning. Here, we repeated the experiment using event-related potentials (ERPs), and we found that Go-stimulus locked ERPs depended on the compatibility relationship between the Go-stimulus and the response effect. In general, this supports the interpretation of the behavioral data. More specifically, differences in the ERPs between compatible and incompatible Go stimuli were found for the early perceptual P1 component and the later frontal P2 component. P1 differences were found only in the second half of the experiment and for long stimulus onset asynchronies (SOAs) between imperative stimulus and Go-stimulus, i.e., when the effect was fully anticipated and the perceptual system was prepared for the effect-compatible Go-stimulus. P2 amplitudes, likely associated with evaluation and conflict detection, were larger when Go-stimulus and effect were incompatible; presumably, incompatibility increased the difficulty of effect anticipation. Onset of response-locked lateralized readiness potentials (R-LRPs) occurred earlier under incompatible conditions indicating extended motor processing. Together, these results strongly suggest that effect anticipation affects all (i.e., perceptual, cognitive, and motor) phases of response preparation. PMID- 26858622 TI - No Evidence for Memory Decontextualization across One Night of Sleep. AB - Sleep after learning strengthens memory consolidation. According to the active system consolidation hypothesis, sleep supports the integration of newly acquired memories into cortical knowledge networks, presumably accompanied by a process of decontextualization of the memory trace (i.e., a gradual loss of memory for the learning context). However, the availability of contextual information generally facilitates memory recall and studies on the interaction of sleep and context on memory retrieval have revealed inconsistent results. Here, we do not find any evidence for a role of sleep in the decontextualization of newly learned declarative memories. In two separate studies, 104 healthy young adults incidentally learned words associated with a context. After a 12 h retention interval filled with either sleep or wakefulness, recall (Experiment 1) or recognition (Experiment 2) was tested with the same or different context. Overall, memory retrieval was significantly improved when the learning context was reinstated, as compared to a different context. However, this context effect of memory was not modulated by sleep vs. wakefulness. These findings argue against a decontextualization of memories, at least across a single night of sleep. PMID- 26858624 TI - Response: Commentary: Cortical responses to salient nociceptive and not nociceptive stimuli in vegetative and minimal conscious state. PMID- 26858623 TI - Domain General Sequence Operations Contribute to Pre-SMA Involvement in Visuo spatial Processing. AB - This study used 3T MRI to elucidate the functional role of supplementary motor area (SMA) in relation to visuo-spatial processing. A localizer task contrasting sequential number subtraction and repetitive button pressing was used to functionally delineate non-motor sequence processing in pre-SMA, and activity in SMA-proper associated with motor sequencing. Patterns of BOLD responses in these regions were then contrasted to those from two tasks of visuo-spatial processing. In one task participants performed Mental Rotation (MR) in which recognition memory judgments were made to previously memorized 2D novel patterns across image plane rotations. The other task involved abstract grid navigation (GN) in which observers computed a series of imagined location shifts in response to directional (arrow) cues around a mental grid. The results showed overlapping activation in pre-SMA for sequential subtraction and both visuo-spatial tasks. These results suggest that visuo-spatial processing is supported by non-motor sequence operations that involve pre-SMA. More broadly, these data further highlight the functional heterogeneity of pre-SMA, and show that its role extends to processes beyond the planning and online control of movement. PMID- 26858625 TI - Mismatch negativity and neural adaptation: Two sides of the same coin. Response: Commentary: Visual mismatch negativity: a predictive coding view. PMID- 26858627 TI - Lesion Mapping the Four-Factor Structure of Emotional Intelligence. AB - Emotional intelligence (EI) refers to an individual's ability to process and respond to emotions, including recognizing the expression of emotions in others, using emotions to enhance thought and decision making, and regulating emotions to drive effective behaviors. Despite their importance for goal-directed social behavior, little is known about the neural mechanisms underlying specific facets of EI. Here, we report findings from a study investigating the neural bases of these specific components for EI in a sample of 130 combat veterans with penetrating traumatic brain injury. We examined the neural mechanisms underlying experiential (perceiving and using emotional information) and strategic (understanding and managing emotions) facets of EI. Factor scores were submitted to voxel-based lesion symptom mapping to elucidate their neural substrates. The results indicate that two facets of EI (perceiving and managing emotions) engage common and distinctive neural systems, with shared dependence on the social knowledge network, and selective engagement of the orbitofrontal and parietal cortex for strategic aspects of emotional information processing. The observed pattern of findings suggests that sub-facets of experiential and strategic EI can be characterized as separable but related processes that depend upon a core network of brain structures within frontal, temporal and parietal cortex. PMID- 26858629 TI - Why Do Some Find it Hard to Disagree? An fMRI Study. AB - People often find it hard to disagree with others, but how this disposition varies across individuals or how it is influenced by social factors like other people's level of expertise remains little understood. Using functional magnetic resonance imaging (fMRI), we found that activity across a network of brain areas [comprising posterior medial frontal cortex (pMFC), anterior insula (AI), inferior frontal gyrus (IFG), lateral orbitofrontal cortex, and angular gyrus] was modulated by individual differences in the frequency with which participants actively disagreed with statements made by others. Specifically, participants who disagreed less frequently exhibited greater brain activation in these areas when they actually disagreed. Given the role of this network in cognitive dissonance, our results suggest that some participants had more trouble disagreeing due to a heightened cognitive dissonance response. Contrary to expectation, the level of expertise (high or low) had no effect on behavior or brain activity. PMID- 26858628 TI - Neurologic Music Therapy Training for Mobility and Stability Rehabilitation with Parkinson's Disease - A Pilot Study. AB - Idiopathic Parkinson's Disease (PD) is a progressive condition with gait disturbance and balance disorder as the main symptoms. Previous research studies focused on the application of Rhythmic Auditory Stimulation (RAS) in PD gait rehabilitation. The key hypothesis of this pilot study, however, assumes the major role of the combination of all three Neurologic Music Therapy (NMT) sensorimotor techniques in improving spatio-temporal gait parameters, and postural stability in the course of PD. The 55 PD-diagnosed subjects invited to the study were divided into two groups: 30 in the experimental and 25 in the control group. Inclusion criteria included Hoehn and Yahr stages 2 or 3, the ability to walk independently without any aid and stable pharmacological treatment for the duration of the experiment. In order to evaluate the efficacy of the chosen therapy procedure the following measures were applied: Optoelectrical 3D Movement Analysis, System BTS Smart for gait, and Computerized Dynamic Posturography CQ Stab for stability and balance. All measures were conducted both before and after the therapy cycle. The subjects from the experimental group attended music therapy sessions four times a week for 4 weeks. Therapeutic Instrumental Music Performance (TIMP), Pattern Sensory Enhancement (PSE) and RAS were used in every 45-min session for practicing daily life activities, balance, pre-gait, and gait pattern. Percussion instruments, the metronome and rhythmic music were the basis for each session. The subjects from the control group were asked to stay active and perform daily life activities between the measures. The research showed that the combination of the three NMT sensorimotor techniques can be used to improve gait and other rhythmical activities in PD rehabilitation. The results demonstrated significant improvement in the majority of the spatiotemporal gait parameters in the experimental group in comparison to the control group. In the stability tests with eyes closed, substantial differences were revealed, indicating improvement of proprioception (the sense of body position and movement). These findings suggest a new compensatory strategy for movement and postural control through the use of the auditory system. PMID- 26858630 TI - Editorial: Abstract Mathematical Cognition. PMID- 26858626 TI - Neurocognitive and Neuroplastic Mechanisms of Novel Clinical Signs in CRPS. AB - Complex regional pain syndrome (CRPS) is a chronic, debilitating pain condition that usually arises after trauma to a limb, but its precise etiology remains elusive. Novel clinical signs based on body perceptual disturbances have been reported, but their pathophysiological mechanisms remain poorly understood. Investigators have used functional neuroimaging techniques (including MEG, EEG, fMRI, and PET) to study changes mainly within the somatosensory and motor cortices. Here, we provide a focused review of the neuroimaging research findings that have generated insights into the potential neurocognitive and neuroplastic mechanisms underlying perceptual disturbances in CRPS. Neuroimaging findings, particularly with regard to somatosensory processing, have been promising but limited by a number of technique-specific factors (such as the complexity of neuroimaging investigations, poor spatial resolution of EEG/MEG, and use of modeling procedures that do not draw causal inferences) and more general factors including small samples sizes and poorly characterized patients. These factors have led to an underappreciation of the potential heterogeneity of pathophysiology that may underlie variable clinical presentation in CRPS. Also, until now, neurological deficits have been predominantly investigated separately from perceptual and cognitive disturbances. Here, we highlight the need to identify neurocognitive phenotypes of patients with CRPS that are underpinned by causal explanations for perceptual disturbances. We suggest that a combination of larger cohorts, patient phenotyping, the use of both high temporal, and spatial resolution neuroimaging methods, and the identification of simplified biomarkers is likely to be the most fruitful approach to identifying neurocognitive phenotypes in CRPS. Based on our review, we explain how such phenotypes could be characterized in terms of hierarchical models of perception and corresponding disturbances in recurrent processing involving the somatosensory, salience and executive brain networks. We also draw attention to complementary neurological factors that may explain some CRPS symptoms, including the possibility of central neuroinflammation and neuronal atrophy, and how these phenomena may overlap but be partially separable from neurocognitive deficits. PMID- 26858631 TI - Bayesian Modeling of the Dynamics of Phase Modulations and their Application to Auditory Event Related Potentials at Different Loudness Scales. AB - We study the effect of long-term habituation signatures of auditory selective attention reflected in the instantaneous phase information of the auditory event related potentials (ERPs) at four distinct stimuli levels of 60, 70, 80, and 90 dB SPL. The analysis is based on the single-trial level. The effect of habituation can be observed in terms of the changes (jitter) in the instantaneous phase information of ERPs. In particular, the absence of habituation is correlated with a consistently high phase synchronization over ERP trials. We estimate the changes in phase concentration over trials using a Bayesian approach, in which the phase is modeled as being drawn from a von Mises distribution with a concentration parameter which varies smoothly over trials. The smoothness assumption reflects the fact that habituation is a gradual process. We differentiate between different stimuli based on the relative changes and absolute values of the estimated concentration parameter using the proposed Bayesian model. PMID- 26858632 TI - Neural Information Processing in Cognition: We Start to Understand the Orchestra, but Where is the Conductor? AB - Research in neural information processing has been successful in the past, providing useful approaches both to practical problems in computer science and to computational models in neuroscience. Recent developments in the area of cognitive neuroscience present new challenges for a computational or theoretical understanding asking for neural information processing models that fulfill criteria or constraints from cognitive psychology, neuroscience and computational efficiency. The most important of these criteria for the evaluation of present and future contributions to this new emerging field are listed at the end of this article. PMID- 26858633 TI - Erratum: Addendum: Models of Metaplasticity: A Review of Concepts. AB - [This corrects the article on p. 138 in vol. 9, PMID: 26617512.]. PMID- 26858634 TI - Exploring Combinations of Different Color and Facial Expression Stimuli for Gaze Independent BCIs. AB - BACKGROUND: Some studies have proven that a conventional visual brain computer interface (BCI) based on overt attention cannot be used effectively when eye movement control is not possible. To solve this problem, a novel visual-based BCI system based on covert attention and feature attention has been proposed and was called the gaze-independent BCI. Color and shape difference between stimuli and backgrounds have generally been used in examples of gaze-independent BCIs. Recently, a new paradigm based on facial expression changes has been presented, and obtained high performance. However, some facial expressions were so similar that users couldn't tell them apart, especially when they were presented at the same position in a rapid serial visual presentation (RSVP) paradigm. Consequently, the performance of the BCI is reduced. NEW METHOD: In this paper, we combined facial expressions and colors to optimize the stimuli presentation in the gaze-independent BCI. This optimized paradigm was called the colored dummy face pattern. It is suggested that different colors and facial expressions could help users to locate the target and evoke larger event-related potentials (ERPs). In order to evaluate the performance of this new paradigm, two other paradigms were presented, called the gray dummy face pattern and the colored ball pattern. COMPARISON WITH EXISTING METHOD(S): The key point that determined the value of the colored dummy faces stimuli in BCI systems was whether the dummy face stimuli could obtain higher performance than gray faces or colored balls stimuli. Ten healthy participants (seven male, aged 21-26 years, mean 24.5 +/- 1.25) participated in our experiment. Online and offline results of four different paradigms were obtained and comparatively analyzed. RESULTS: The results showed that the colored dummy face pattern could evoke higher P300 and N400 ERP amplitudes, compared with the gray dummy face pattern and the colored ball pattern. Online results showed that the colored dummy face pattern had a significant advantage in terms of classification accuracy (p < 0.05) and information transfer rate (p < 0.05) compared to the other two patterns. CONCLUSIONS: The stimuli used in the colored dummy face paradigm combined color and facial expressions. This had a significant advantage in terms of the evoked P300 and N400 amplitudes and resulted in high classification accuracies and information transfer rates. It was compared with colored ball and gray dummy face stimuli. PMID- 26858635 TI - Dendrite and Axon Specific Geometrical Transformation in Neurite Development. AB - We propose a model of neurite growth to explain the differences in dendrite and axon specific neurite development. The model implements basic molecular kinetics, e.g., building protein synthesis and transport to the growth cone, and includes explicit dependence of the building kinetics on the geometry of the neurite. The basic assumption was that the radius of the neurite decreases with length. We found that the neurite dynamics crucially depended on the relationship between the rate of active transport and the rate of morphological changes. If these rates were in the balance, then the neurite displayed axon specific development with a constant elongation speed. For dendrite specific growth, the maximal length was rapidly saturated by degradation of building protein structures or limited by proximal part expansion reaching the characteristic cell size. PMID- 26858636 TI - BrainLiner: A Neuroinformatics Platform for Sharing Time-Aligned Brain-Behavior Data. AB - Data-driven neuroscience aims to find statistical relationships between brain activity and task behavior from large-scale datasets. To facilitate high throughput data processing and modeling, we created BrainLiner as a web platform for sharing time-aligned, brain-behavior data. Using an HDF5-based data format, BrainLiner treats brain activity and data related to behavior with the same salience, aligning both behavioral and brain activity data on a common time axis. This facilitates learning the relationship between behavior and brain activity. Using a common data file format also simplifies data processing and analyses. Properties describing data are unambiguously defined using a schema, allowing machine-readable definition of data. The BrainLiner platform allows users to upload and download data, as well as to explore and search for data from the web platform. A WebGL-based data explorer can visualize highly detailed neurophysiological data from within the web browser, and a data-driven search feature allows users to search for similar time windows of data. This increases transparency, and allows for visual inspection of neural coding. BrainLiner thus provides an essential set of tools for data sharing and data-driven modeling. PMID- 26858637 TI - Amidated and Ibuprofen-Conjugated Kyotorphins Promote Neuronal Rescue and Memory Recovery in Cerebral Hypoperfusion Dementia Model. AB - Chronic brain ischemia is a prominent risk factor for neurological dysfunction and progression for dementias, including Alzheimer's disease (AD). In rats, permanent bilateral common carotid artery occlusion (2VO) causes a progressive neurodegeneration in the hippocampus, learning deficits and memory loss as it occurs in AD. Kyotorphin (KTP) is an endogenous antinociceptive dipeptide whose role as neuromodulator/neuroprotector has been suggested. Recently, we designed two analgesic KTP-derivatives, KTP-amide (KTP-NH2) and KTP-NH2 linked to ibuprofen (IbKTP-NH2) to improve KTP brain targeting. This study investigated the effects of KTP-derivatives on cognitive/behavioral functions (motor/spatial memory/nociception) and hippocampal pathology of female rats in chronic cerebral hypoperfusion (2VO-rat model). 2VO-animals were treated with KTP-NH2 or IbKTP-NH2 for 7 days at weeks 2 and 5 post-surgery. After behavioral testing (week 6), coronal sections of hippocampus were H&E-stained or immunolabeled for the cellular markers GFAP (astrocytes) and NFL (neurons). Our findings show that KTP derivatives, mainly IbKTP-NH2, enhanced cognitive impairment of 2VO-animals and prevented neuronal damage in hippocampal CA1 subfield, suggesting their potential usefulness for the treatment of dementia. PMID- 26858638 TI - Limited Effect of Dopaminergic Medication on Straight Walking and Turning in Early-to-Moderate Parkinson's Disease during Single and Dual Tasking. AB - BACKGROUND: In Parkinson's disease (PD), the effects of dopaminergic medication on straight walking and turning were mainly investigated under single tasking (ST) conditions. However, multitasking situations are considered more daily relevant. METHODS: Thirty-nine early-to-moderate PD patients performed the following standardized ST and dual tasks as fast as possible for 1 min during On- and Off-medication while wearing inertial sensors: straight walking and turning, checking boxes, and subtracting serial 7s. Quantitative gait parameters as well as velocity of the secondary tasks were analyzed. RESULTS: The following parameters improved significantly in On-medication during ST: gait velocity during straight walking (p = 0.03); step duration (p = 0.048) and peak velocity (p = 0.04) during turning; velocity of checking boxes during ST (p = 0.04) and DT (p = 0.04). Velocity of checking boxes was the only parameter that also improved during DT. CONCLUSION: These results suggest that dopaminergic medication does not relevantly influence straight walking and turning in early-to-moderate PD during DT. PMID- 26858640 TI - Commentary: Age-related neurodegenerative disease research needs aging models. PMID- 26858639 TI - Thromboxane A2 Receptor Stimulation Enhances Microglial Interleukin-1beta and NO Biosynthesis Mediated by the Activation of ERK Pathway. AB - BACKGROUND AND PURPOSE: Thromboxane A2 (TXA2) receptors (TP) interact with the ligand TXA2 to induce platelet aggregation and regulate hemostasis. Recently TP mediated signaling has been suggested to function in multiple cell types in the brain. In this report, we aim to study the expression and physiological role of TP in microglia, in particular after brain ischemia. METHODS: Ischemic brain sections were analyzed for TP expression. Microglial cell line and primary microglia were cultured, or neuronal cell line co-culture system was used to determine the TP mediated signaling in inflammation and microglia activation. RESULTS: We found that the TP level was significantly increased in ipsilateral mouse brain tissue at 24 h after ischemia-reperfusion, which was also found to partly co-localize with CD11b, a marker for microglial and infiltrated monocyte/macrophage, in peri-infarct area. Immunofluorescence staining of primary microglia and microglial cell line BV2 revealed the predominant membrane distribution of TP. Conditioned culture media from TP agonist U46619-treated BV2 cells decreased neuronal SH-SY5Y cell viability and induced apoptotic morphological changes. Furthermore, U46619 enhanced IL-1beta, IL-6, and iNOS mRNA expression as well as IL-1beta and NO releases in BV2 cells or primary microglia. Such stimulation could be attenuated by TP antagonist SQ29548 or MEK inhibitor U0126. The dose- and time-dependent extracellular-signal-regulated kinase (ERK) phosphorylation induced by U46619 further demonstrated ERK signaling-mediated microglia activation by TP agonist. CONCLUSION: This study has shown a novel role of TP in microglia activation via the ERK signaling pathway, which provides insights for the management of neuroinflammation in diseases like cerebral infarction. PMID- 26858641 TI - NADPH Oxidase/ROS-Dependent VCAM-1 Induction on TNF-alpha-Challenged Human Cardiac Fibroblasts Enhances Monocyte Adhesion. AB - The inflammation-dependent adhesion molecule expressions are characterized in cardiovascular diseases and myocardial tissue infiltrations. Several pro inflammatory cytokines are elevated in the acute myocardial injury and infarction. Tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine, is raised in the injury tissues and inflammatory regions and involved in the pathogenesis of cardiac injury, inflammation, and apoptosis. In fibroblasts, TNF alpha-triggered expression of vascular cell adhesion molecule (VCAM)-1 aggravated the heart inflammation. However, the mechanisms underlying TNF-alpha-mediated VCAM-1 expression in cardiac fibroblasts remain unclear. Here, the primary cultured human cardiac fibroblasts (HCFs) were used to investigate the effects of TNF-alpha on VCAM-1 expression. The molecular evidence, including protein, mRNA, and promoter analyses, indicated that TNF-alpha-induced VCAM-1 gene expression is mediated through the TNFR-dependent manner. Activation of TNF-alpha/TNFR system triggered PKCalpha-dependent NADPH oxidase (Nox)/reactive oxygen species (ROS) signal linking to MAPK cascades, and then led to activation of the transcription factor, AP-1. Moreover, the results of mRNA and promoter assay demonstrated that c-Jun/AP-1 phosphorylated by TNF-alpha turns on VCAM-1 gene expression. Subsequently, up-regulated VCAM-1 on the cell surface of TNF-alpha-challenged HCFs increased the number of monocytes adhering to these cells. These results indicated that in HCFs, activation of AP-1 by PKCalpha-dependent Nox/ROS/MAPKs cascades is required for TNF-alpha-induced VCAM-1 expression. To clarify the mechanisms of TNF-alpha-induced VCAM-1 expression in HCFs may provide therapeutic strategies for heart injury and inflammatory diseases. PMID- 26858642 TI - Mechanism of Action of the Novel Nickel(II) Complex in Simultaneous Reactivation of the Apoptotic Signaling Networks Against Human Colon Cancer Cells. AB - The aim of this study was to evaluate the cytotoxic potential of a novel nickel(II) complex (NTC) against WiDr and HT-29 human colon cancer cells by determining the IC50 using the standard MTT assay. The NTC displayed a strong suppressive effect on colon cancer cells with an IC50 value of 6.07 +/- 0.22 MUM and 6.26 +/- 0.13 MUM against WiDr and HT-29 respectively, after 24 h of treatment. Substantial reduction in the mitochondrial membrane potential and increase in the release of cytochrome c from the mitochondria directed the induction of the intrinsic apoptosis pathway by the NTC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. The NTC was also shown to activate the extrinsic pathway of apoptosis via activation of caspase-8 which is linked to the suppression of NF-kappaB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up regulation of glutathione reductase expression was quantified by qPCR. Results of the current work indicates that NTC possess a potent cancer cell abolishing activity by simultaneous induction of intrinsic and extrinsic pathways of apoptosis in colon cancer cell lines. PMID- 26858644 TI - Cross-Comparison of Exome Analysis, Next-Generation Sequencing of Amplicons, and the iPLEX((r)) ADME PGx Panel for Pharmacogenomic Profiling. AB - Whole-exome sequencing (WES) has been widely used for analysis of human genetic diseases, but its value for the pharmacogenomic profiling of individuals is not well studied. Initially, we performed an in-depth evaluation of the accuracy of WES variant calling in the pharmacogenes CYP2D6 and CYP2C19 by comparison with MiSeq((r)) amplicon sequencing data (n = 36). This analysis revealed that the concordance rate between WES and MiSeq((r)) was high, achieving 99.60% for variants that were called without exceeding the truth-sensitivity threshold (99%), defined during variant quality score recalibration (VQSR). Beyond this threshold, the proportion of discordant calls increased markedly. Subsequently, we expanded our findings beyond CYP2D6 and CYP2C19 to include more genes genotyped by the iPLEX((r)) ADME PGx Panel in the subset of twelve samples. WES performed well, agreeing with the genotyping panel in approximately 99% of the selected pass-filter variant calls. Overall, our results have demonstrated WES to be a promising approach for pharmacogenomic profiling, with an estimated error rate of lower than 1%. Quality filters, particularly VQSR, are important for reducing the number of false variants. Future studies may benefit from examining the role of WES in the clinical setting for guiding drug therapy. PMID- 26858643 TI - MicroRNA-mRNA Pairs Associated with Outcome in AML: From In Vitro Cell-Based Studies to AML Patients. AB - Cytarabine is the primary chemotherapeutic agent used for treatment of acute myeloid leukemia (AML). Disease relapse after initial remission remains one of the most pressing therapeutic challenges in the treatment of AML. Relapsed disease is often resistant to cytarabine and subsequent salvage therapy is ineffective. Recent studies have shown that some microRNAs (miRNAs) are associated with prognosis, but have not yet explored the role of miRNAs in cellular response to cytarabine. We identified 20 miRNAs that associate with the in vitro cytarabine chemo-sensitivity or apoptotic response of eight AML cell lines. Out of the 20 miRNAs, data on 18 miRNAs was available in AML patients from The Cancer Genome Atlas database. Our stepwise-integrated analyses (step 1 - miRNA-target mRNA that were significantly correlated in AML patients; step 2 - mRNAs from step 1 with significant association with overall survival (OS)) identified 23 unique miRNA-mRNA pairs predictive of OS in AML patients. As expected HOX genes (HOXA9, HOXB7, and HOXA10) were identified to be regulated by miRs as well as predictive of worse OS. Additionally, miR107-Myb, miR-378 granzyme B involved in granzyme signaling and miR10a-MAP4K4 were identified to be predictive of outcome through integrated analysis. Although additional functional validations to establish clinical/pharmacologic importance of miRNA-mRNA pairs are needed, our results from RNA electrophoretic mobility shift assay confirmed binding of miR-10a, miR-378, and miR-107 with their target genes GALNT1, GZMB, and MYB, respectively. Integration of pathogenic and pharmacologically significant miRNAs and miRNA-mRNA relationships identified in our study opens up opportunities for development of targeted/miRNA-directed therapies. PMID- 26858645 TI - Anticancer Activity of Garcinia morella on T-Cell Murine Lymphoma Via Apoptotic Induction. AB - Traditional knowledge (TK) based medicines have gained worldwide attention and presently the scientific community is focussing on proper pharmacological validation and identification of lead compounds for the treatment of various diseases. The North East region of India is the home of valuable traditional herbal remedies. Garcinia morella Desr. (Guttiferae) is one such medicinal plant used by traditional healers for the treatment of inflammatory disorders. The present study was aimed to evaluate the antioxidant and anticancer activity of methanol extracts of the leaf, bark and fruit of G. morella (GM) in different in vitro and in vivo experimental conditions. The results of this study showed that GM methanol extracts possessed in vitro antioxidant and anticancer properties, where the fruit extract (GF) showed maximum activity. The anticancer activity was further confirmed by the results of in vivo administration of GF (200 mg/kg) for ten days to Dalton's lymphoma (DLA) induced mice. GF extract significantly increased the mean survival time (MST) of the animals, decreased the tumor volume and restored the hematological and biochemical parameters. The present study for the first time reported the anticancer property of GF on DLA. Further from the experiments conducted to elucidate the mechanism of action of GF on DLA, it can be concluded that GF exerts its anticancer effect through induction of caspases and DNA fragmentation that ultimately leads to apoptosis. However, further experimentation is required to elucidate the active principle and validate these findings in various in vivo settings. PMID- 26858646 TI - Editorial: Frontiers in the Pharmacological Manipulation of Intracellular cAMP Levels. PMID- 26858647 TI - ATP-induced P2X Receptor-Dependent Large Pore Formation: How Much Do We Know? PMID- 26858649 TI - Extracellular Cysteine in Connexins: Role as Redox Sensors. AB - Connexin-based channels comprise hemichannels and gap junction channels. The opening of hemichannels allow for the flux of ions and molecules from the extracellular space into the cell and vice versa. Similarly, the opening of gap junction channels permits the diffusional exchange of ions and molecules between the cytoplasm and contacting cells. The controlled opening of hemichannels has been associated with several physiological cellular processes; thereby unregulated hemichannel activity may induce loss of cellular homeostasis and cell death. Hemichannel activity can be regulated through several mechanisms, such as phosphorylation, divalent cations and changes in membrane potential. Additionally, it was recently postulated that redox molecules could modify hemichannels properties in vitro. However, the molecular mechanism by which redox molecules interact with hemichannels is poorly understood. In this work, we discuss the current knowledge on connexin redox regulation and we propose the hypothesis that extracellular cysteines could be important for sensing changes in redox potential. Future studies on this topic will offer new insight into hemichannel function, thereby expanding the understanding of the contribution of hemichannels to disease progression. PMID- 26858651 TI - Toxic Effect of Blood Feeding in Male Mosquitoes. AB - Blood- and sugar feeding of female mosquitoes has been frequently observed in the laboratory and in the field, but only sugar feeding of males has been reported. Here, we describe for the first time that Culex quinquefasciatus males feed on blood as well. Blood feeding easily happened on a blood-soaked cotton roll and, to a lesser extent, through a thin artificial layer. Mating history of a male specimen does not affect his blood feeding behavior. Male mosquitoes feed on blood even when they have a readily available sugar source. Nevertheless, feeding on blood reduces the survival rate of males to just a few days, as compared to more than a month for mosquitoes fed only on sugar. Comparing survival of male mosquitoes fed on blood only, sugar only, and a combination of both clearly demonstrated that mortality is not affected by malnutrition (reduced sugar levels), but rather due to ingested blood. On average male mosquitoes ingested ca. 0.5 MUl of blood, i.e., about 10% of the amount of blood ingested by an engorged female. Although this unexpected observation of blood feeding in the laboratory by male mosquitoes is interesting, structural impairment prevents male feeding on vertebrate blood. In agreement with the literature, male and female proboscises and stylets were in general of similar size, but male mandibles were significantly shorter than female counterparts, thus explaining their inability to pierce through skin layers. PMID- 26858650 TI - Personalized Cardiovascular Disease Prediction and Treatment-A Review of Existing Strategies and Novel Systems Medicine Tools. AB - Cardiovascular disease (CVD) continues to constitute the leading cause of death globally. CVD risk stratification is an essential tool to sort through heterogeneous populations and identify individuals at risk of developing CVD. However, applications of current risk scores have recently been shown to result in considerable misclassification of high-risk subjects. In addition, despite long standing beneficial effects in secondary prevention, current CVD medications have in a primary prevention setting shown modest benefit in terms of increasing life expectancy. A systems biology approach to CVD risk stratification may be employed for improving risk-estimating algorithms through addition of high throughput derived omics biomarkers. In addition, modeling of personalized benefit-of-treatment may help in guiding choice of intervention. In the area of medicine, realizing that CVD involves perturbations of large complex biological networks, future directions in drug development may involve moving away from a reductionist approach toward a system level approach. Here, we review current CVD risk scores and explore how novel algorithms could help to improve the identification of risk and maximize personalized treatment benefit. We also discuss possible future directions in the development of effective treatment strategies for CVD through the use of genome-scale metabolic models (GEMs) as well as other biological network-based approaches. PMID- 26858648 TI - Drug-Induced Liver Toxicity and Prevention by Herbal Antioxidants: An Overview. AB - The liver is the center for drug and xenobiotic metabolism, which is influenced most with medication/xenobiotic-mediated toxic activity. Drug-induced hepatotoxicity is common and its actual frequency is hard to determine due to underreporting, difficulties in detection or diagnosis, and incomplete observation of exposure. The death rate is high, up to about 10% for drug-induced liver damage. Endorsed medications represented >50% of instances of intense liver failure in a study from the Acute Liver Failure Study Group of the patients admitted in 17 US healing facilities. Albeit different studies are accessible uncovering the mechanistic aspects of medication prompted hepatotoxicity, we are in the dilemma about the virtual story. The expanding prevalence and effectiveness of Ayurveda and natural products in the treatment of various disorders led the investigators to look into their potential in countering drug induced liver toxicity. Several natural products have been reported to date to mitigate the drug-induced toxicity. The dietary nature and less adverse reactions of the natural products provide them an extra edge over other candidates of supplementary medication. In this paper, we have discussed the mechanism involved in drug-induced liver toxicity and the potential of herbal antioxidants as supplementary medication. PMID- 26858652 TI - Heterogeneity of the Peripheral Circadian Systems in Drosophila melanogaster: A Review. AB - Circadian rhythms in organisms are involved in many aspects of metabolism, physiology, and behavior. In many animals, these rhythms are produced by the circadian system consisting of a central clock located in the brain and peripheral clocks in various peripheral tissues. The oscillatory machinery and entrainment mechanism of peripheral clocks vary between different tissues and organs. The relationship between the central and peripheral clocks is also tissue dependent. Here we review the heterogeneous nature of peripheral circadian clocks in the fruit fly Drosophila melanogaster and their dependence on the central clock, and discuss their significance in the temporal organization of physiology in peripheral tissues/organs. PMID- 26858653 TI - Na,K-ATPase Isozymes in Colorectal Cancer and Liver Metastases. AB - The goal of this study was to define Na,K-ATPase alpha and beta subunit isoform expression and isozyme composition in colorectal cancer cells and liver metastases. The alpha1, alpha3, and beta1 isoforms were the most highly expressed in tumor cells and metastases; in the plasma membrane of non-neoplastic cells and mainly in a cytoplasmic location in tumor cells. alpha1beta1 and alpha3beta1 isozymes found in tumor and metastatic cells exhibit the highest and lowest Na(+) affinity respectively and the highest K(+) affinity. Mesenchymal cell isozymes possess an intermediate Na(+) affinity and a low K(+) affinity. In cancer, these ions are likely to favor optimal conditions for the function of nuclear enzymes involved in mitosis, especially a high intra-nuclear K(+) concentration. A major and striking finding of this study was that in liver, metastasized CRC cells express the alpha3beta1 isozyme. Thus, the alpha3beta1 isozyme could potentially serve as a novel exploratory biomarker of CRC metastatic cells in liver. PMID- 26858654 TI - Is Resistance Training to Muscular Failure Necessary? PMID- 26858655 TI - Locomotor-Respiratory Coupling in Wheelchair Racing Athletes: A Pilot Study. AB - PURPOSE: In wheelchair racing, respiratory muscles of the rib cage are concomitantly involved in non-ventilatory functions during wheelchair propulsion. However, the relationship between locomotor-respiratory coupling (LRC: the ratio between push and breathing frequency), respiratory parameters and work efficiency is unknown. Therefore, the aim of the present study was to investigate the LRC in wheelchair racers over different race distances. METHODS: Eight trained and experienced wheelchair racers completed three time-trials over the distances of 400, 800, and 5000 m on a training roller in randomized order. During the time trials, ventilatory and gas exchange variables as well as push frequency were continuously registered to determine possible LRC strategies. RESULTS: Four different coupling ratios were identified, namely 1:1; 2:1, 3:1 as well as a 1:1/2:1 alternating type, respectively. The 2:1 coupling was the most dominant type. The 1:1/2:1 alternating coupling type was found predominantly during the 400 m time-trial. Longer race distances tended to result in an increased coupling ratio (e.g., from 1:1 toward 2:1), and an increase in coupling ratio toward a more efficient respiration was found over the 5000 m distance. A significant correlation (r = 0.80, p < 0.05) between respiratory frequency and the respiratory equivalent for oxygen was found for the 400 m and the 800 m time trials. CONCLUSIONS: These findings suggest that a higher coupling ratio indicates enhanced breathing work efficiency with a concomitant deeper and slower respiration during wheelchair racing. Thus, the selection of an appropriate LRC strategy may help to optimize wheelchair racing performance. PMID- 26858657 TI - Inhibition of PDE5 Restores Depressed Baroreflex Sensitivity in Renovascular Hypertensive Rats. AB - Renal artery stenosis is frequently associated with resistant hypertension, which is defined as failure to normalize blood pressure (BP) even when combined drugs are used. Inhibition of PDE5 by sildenafil has been shown to increase endothelial function and decrease blood pressure in experimental models. However, no available study evaluated the baroreflex sensitivity nor autonomic balance in renovascular hypertensive rats treated with sildenafil. In a translational medicine perspective, our hypothesis is that sildenafil could improve autonomic imbalance and baroreflex sensitivity, contributing to lower blood pressure. Renovascular hypertensive 2-kidney-1-clip (2K1C) and sham rats were treated with sildenafil (45 mg/Kg/day) during 7 days. At the end of treatment, BP and heart rate (HR) were recorded in conscious rats after a 24-h-recovery period. Spontaneous and drug-induced baroreflex sensitivity and autonomic tone were evaluated; in addition, lipid peroxidation was measured in plasma samples. Treatment was efficient in increasing both spontaneous and induced baroreflex sensitivity in treated hypertensive animals. Inhibition of PDE5 was also capable of ameliorating autonomic imbalance in 2K1C rats and decreasing systemic oxidative stress. Taken together, these beneficial effects resulted in significant reductions in BP without affecting HR. We suggest that sildenafil could be considered as a promising alternative to treat resistant hypertension. PMID- 26858656 TI - Placental Responses to Changes in the Maternal Environment Determine Fetal Growth. AB - Placental responses to maternal perturbations are complex and remain poorly understood. Altered maternal environment during pregnancy such as hypoxia, stress, obesity, diabetes, toxins, altered nutrition, inflammation, and reduced utero-placental blood flow may influence fetal development, which can predispose to diseases later in life. The placenta being a metabolically active tissue responds to these perturbations by regulating the fetal supply of nutrients and oxygen and secretion of hormones into the maternal and fetal circulation. We have proposed that placental nutrient sensing integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensing signaling pathways to balance fetal demand with the ability of the mother to support pregnancy by regulating maternal physiology, placental growth, and placental nutrient transport. Emerging evidence suggests that the nutrient-sensing signaling pathway mechanistic target of rapamycin (mTOR) plays a central role in this process. Thus, placental nutrient sensing plays a critical role in modulating maternal-fetal resource allocation, thereby affecting fetal growth and the life-long health of the fetus. PMID- 26858658 TI - Reactivity to Social Stress in Subclinical Social Anxiety: Emotional Experience, Cognitive Appraisals, Behavior, and Physiology. AB - Recent research indicates that subclinical social anxiety is associated with dysfunctions at multiple psychological and biological levels, in a manner that seems reminiscent of social anxiety disorder (SAD). This study aimed to describe multidimensional responses to laboratory-induced social stress in an analog sample selected for social anxiety symptoms. State anxiety, cognitive biases related to negative social evaluation, speech anxiety behaviors, and cortisol reactivity were assessed in the Trier Social Stress Test (TSST). Results showed that social anxiety symptoms were associated with increased state anxiety, biased appraisals related to the probability and cost of negative social evaluations, behavioral changes in facial expression that were consistent with speech anxiety, and lower cortisol reactivity. In addition, multiple interrelations between responses in the TSST were found, with positive associations between subjective experience, cognitive appraisals, and observable behavior, as well as negative associations between each of the former two types of response and cortisol reactivity. These results show that in response to social stressors, subclinical social anxiety is associated with significant changes in emotional experience, cognitive appraisals, behaviors, and physiology that could parallel those previously found in SAD samples. PMID- 26858659 TI - Can We Use Neurocognition to Predict Repetition of Self-Harm, and Why Might This Be Clinically Useful? A Perspective. AB - Over 800,000 people die by suicide each year globally, with non-fatal self-harm 20 times more common. With each episode of self-harm, the risks of future self harm and suicide increase, as well as personal and healthcare costs. Therefore, early delineation of those at high risk of future self-harm is important. Historically, research has focused on clinical and demographic factors, but risk assessments based on these have low sensitivity to predict repetition. Various neurocognitive factors have been associated with self-harming behavior, but it is less certain if we can use these factors clinically (i) as risk markers to predict future self-harm and (ii) to become therapeutic targets for interventions. Recent systematic reviews and meta-analyses of behavioral tasks and fMRI studies point to an emerging hypothesis for neurocognition in self-harm: an underactive pre-frontal cortex is unable to respond appropriately to non emotional stimuli, or inhibit a hyperactive emotionally-/threat-driven limbic system. However, there is almost no imaging data examining repetition of self harm. Extrapolating from the non-repetition data, there may be several potential neurocognitive targets for interventions to prevent repeat self-harm: cognitive training; pharmacological regimes to promote non-emotional neurocognition; or other techniques, such as repetitive transcranial magnetic stimulation. Hence, there is an urgent need for imaging studies examining repetition and to test specific hypotheses. Until we investigate the functional neurocognitive basis underlying repetition of self-harm in a systematic manner using second generational imaging techniques, we will be unable to inform third-generational imaging and potential future clinical applications. PMID- 26858661 TI - Understanding the P*S Aspect of Within-Person Variation: A Variance Partitioning Approach. AB - This article reviews a variance partitioning approach to within-person variation based on Generalizability Theory and the Social Relations Model. The approach conceptualizes an important part of within-person variation as Person * Situation (P*S) interactions: differences among persons in their profiles of responses across the same situations. The approach provided the first quantitative method for capturing within-person variation and demonstrated very large P*S effects for a wide range of constructs. These include anxiety, five-factor personality traits, perceived social support, leadership, and task performance. Although P*S effects are commonly very large, conceptual, and analytic obstacles have thwarted consistent progress. For example, how does one develop a psychological, versus purely statistical, understanding of P*S effects? How does one forecast future behavior when the criterion is a P*S effect? How can understanding P*S effects contribute to psychological theory? This review describes potential solutions to these and other problems developed in the course of conducting research on the P*S aspect of social support. Additional problems that need resolution are identified. PMID- 26858662 TI - Subtle Implicit Language Facts Emerge from the Functions of Constructions. AB - Much has been written about the unlikelihood of innate, syntax-specific, universal knowledge of language (Universal Grammar) on the grounds that it is biologically implausible, unresponsive to cross-linguistic facts, theoretically inelegant, and implausible and unnecessary from the perspective of language acquisition. While relevant, much of this discussion fails to address the sorts of facts that generative linguists often take as evidence in favor of the Universal Grammar Hypothesis: subtle, intricate, knowledge about language that speakers implicitly know without being taught. This paper revisits a few often cited such cases and argues that, although the facts are sometimes even more complex and subtle than is generally appreciated, appeals to Universal Grammar fail to explain the phenomena. Instead, such facts are strongly motivated by the functions of the constructions involved. The following specific cases are discussed: (a) the distribution and interpretation of anaphoric one, (b) constraints on long-distance dependencies, PMID- 26858660 TI - Revisiting the Basic Symptom Concept: Toward Translating Risk Symptoms for Psychosis into Neurobiological Targets. AB - In its initial formulation, the concept of basic symptoms (BSs) integrated findings on the early symptomatic course of schizophrenia and first in vivo evidence of accompanying brain aberrations. It argued that the subtle subclinical disturbances in mental processes described as BSs were the most direct self experienced expression of the underlying neurobiological aberrations of the disease. Other characteristic symptoms of psychosis (e.g., delusions and hallucinations) were conceptualized as secondary phenomena, resulting from dysfunctional beliefs and suboptimal coping styles with emerging BSs and/or concomitant stressors. While BSs can occur in many mental disorders, in particular affective disorders, a subset of perceptive and cognitive BSs appear to be specific to psychosis and are currently employed in two alternative risk criteria. However, despite their clinical recognition in the early detection of psychosis, neurobiological research on the aetiopathology of psychosis with neuroimaging methods has only just begun to consider the neural correlate of BSs. This perspective paper reviews the emerging evidence of an association between BSs and aberrant brain activation, connectivity patterns, and metabolism, and outlines promising routes for the use of BSs in aetiopathological research on psychosis. PMID- 26858663 TI - Increased Risk Taking in Relation to Chronic Stress in Adults. AB - Chronic stress is a public health problem that affects a significant part of the population. While the physiological damage it causes is under ongoing scrutiny, its behavioral effects have been overlooked. This is one of the first studies to examine the relation between chronic stress and decision-making, using a standard lottery paradigm. We measured risk taking in the gain domain through binary choices between financially incentivized lotteries. We then measured self reported chronic stress with the Trier Inventory for the Assessment of Chronic Stress (TICS). We additionally collected hair samples in a subsample of volunteers, in order to quantify accumulation of the stress hormone cortisol. We discovered a significant positive, though modest, correlation between self reported chronic stress and risk taking that is stronger for women than for men. This confirms part of the findings in acute stress research that show a connection between higher stress and increased risk taking. However, unlike the biologically-based results from acute stress research, we did not identify a significant relation between hair cortisol and behavior. In line with previous literature, we found a clear gender difference in risk taking and self-reports: women generally take less risk and report slightly higher stress levels than men. We conclude that perceived chronic stress can impact behavior in risky situations. PMID- 26858664 TI - Developmental Dyslexia and Dysgraphia: What can We Learn from the One About the Other? AB - Up to 17% of German school children suffer from reading and writing disabilities. Unlike developmental dyslexia, only few studies have addressed dysgraphia. Presenting a comprehensive overview of the current state of the art in developmental dyslexia and dysgraphia, this paper aims to determine how far existing knowledge about the causes of developmental dyslexia also apply to developmental dysgraphia. To promote understanding of developmental dysgraphia, the paper discusses relevant aspects such as predictors, causes and comorbidities, models of acquisition as well as existing deficit models. A comparison of definitions in the DSM-V and ICD-10 complemented by an overview of the most recent German guideline ought to give the reader deeper insight into this topic. The current issue of growing up bilingually and the connection between reading and writing deficits are also discussed. In conclusion, this paper presents a critical survey of theoretical and practical implications for the diagnostics and treatment of developmental dysgraphia. PMID- 26858665 TI - Cortical Dynamics of Figure-Ground Separation in Response to 2D Pictures and 3D Scenes: How V2 Combines Border Ownership, Stereoscopic Cues, and Gestalt Grouping Rules. AB - The FACADE model, and its laminar cortical realization and extension in the 3D LAMINART model, have explained, simulated, and predicted many perceptual and neurobiological data about how the visual cortex carries out 3D vision and figure ground perception, and how these cortical mechanisms enable 2D pictures to generate 3D percepts of occluding and occluded objects. In particular, these models have proposed how border ownership occurs, but have not yet explicitly explained the correlation between multiple properties of border ownership neurons in cortical area V2 that were reported in a remarkable series of neurophysiological experiments by von der Heydt and his colleagues; namely, border ownership, contrast preference, binocular stereoscopic information, selectivity for side-of-figure, Gestalt rules, and strength of attentional modulation, as well as the time course during which such properties arise. This article shows how, by combining 3D LAMINART properties that were discovered in two parallel streams of research, a unified explanation of these properties emerges. This explanation proposes, moreover, how these properties contribute to the generation of consciously seen 3D surfaces. The first research stream models how processes like 3D boundary grouping and surface filling-in interact in multiple stages within and between the V1 interblob-V2 interstripe-V4 cortical stream and the V1 blob-V2 thin stripe-V4 cortical stream, respectively. Of particular importance for understanding figure-ground separation is how these cortical interactions convert computationally complementary boundary and surface mechanisms into a consistent conscious percept, including the critical use of surface contour feedback signals from surface representations in V2 thin stripes to boundary representations in V2 interstripes. Remarkably, key figure-ground properties emerge from these feedback interactions. The second research stream shows how cells that compute absolute disparity in cortical area V1 are transformed into cells that compute relative disparity in cortical area V2. Relative disparity is a more invariant measure of an object's depth and 3D shape, and is sensitive to figure-ground properties. PMID- 26858667 TI - Observing the Testing Effect using Coursera Video-Recorded Lectures: A Preliminary Study. AB - We investigated the testing effect in Coursera video-based learning. One hundred and twenty-three participants either (a) studied an instructional video-recorded lecture four times, (b) studied the lecture three times and took one recall test, or (c) studied the lecture once and took three tests. They then took a final recall test, either immediately or a week later, through which their learning was assessed. Whereas repeated studying produced better recall performance than did repeated testing when the final test was administered immediately, testing produced better performance when the final test was delayed until a week after. The testing effect was observed using Coursera lectures. Future directions are documented. PMID- 26858666 TI - A Reanalysis of Cognitive-Functional Performance in Older Adults: Investigating the Interaction Between Normal Aging, Mild Cognitive Impairment, Mild Alzheimer's Disease Dementia, and Depression. AB - Depressive symptoms are associated with cognitive-functional impairment in normal aging older adults (NA). However, less is known about this effect on people with mild Cognitive Impairment (MCI) and mild Alzheimer's disease dementia (AD). We investigated this relationship along with the NA-MCI-AD continuum by reanalyzing a previously published dataset. Participants (N = 274) underwent comprehensive neuropsychological assessment including measures of Executive Function, Language/Semantic Memory, Episodic Memory, Visuospatial Abilities, Activities of Daily Living (ADL), and the Geriatric Depression Scale. MANOVA, logistic regression and chi-square tests were performed to assess the association between depression and cognitive-functional performance in each group. In the NA group, depressed participants had a lower performance compared to non-depressed participants in all cognitive and functional domains. However, the same pattern was not observed in the MCI group or in AD. The results suggest a progressive loss of association between depression and worse cognitive-functional performance along the NA-MCI-AD continuum. PMID- 26858669 TI - Quantum-Like Bayesian Networks for Modeling Decision Making. AB - In this work, we explore an alternative quantum structure to perform quantum probabilistic inferences to accommodate the paradoxical findings of the Sure Thing Principle. We propose a Quantum-Like Bayesian Network, which consists in replacing classical probabilities by quantum probability amplitudes. However, since this approach suffers from the problem of exponential growth of quantum parameters, we also propose a similarity heuristic that automatically fits quantum parameters through vector similarities. This makes the proposed model general and predictive in contrast to the current state of the art models, which cannot be generalized for more complex decision scenarios and that only provide an explanatory nature for the observed paradoxes. In the end, the model that we propose consists in a nonparametric method for estimating inference effects from a statistical point of view. It is a statistical model that is simpler than the previous quantum dynamic and quantum-like models proposed in the literature. We tested the proposed network with several empirical data from the literature, mainly from the Prisoner's Dilemma game and the Two Stage Gambling game. The results obtained show that the proposed quantum Bayesian Network is a general method that can accommodate violations of the laws of classical probability theory and make accurate predictions regarding human decision-making in these scenarios. PMID- 26858668 TI - Modeling the Effects of Perceptual Load: Saliency, Competitive Interactions, and Top-Down Biases. AB - A computational model of visual selective attention has been implemented to account for experimental findings on the Perceptual Load Theory (PLT) of attention. The model was designed based on existing neurophysiological findings on attentional processes with the objective to offer an explicit and biologically plausible formulation of PLT. Simulation results verified that the proposed model is capable of capturing the basic pattern of results that support the PLT as well as findings that are considered contradictory to the theory. Importantly, the model is able to reproduce the behavioral results from a dilution experiment, providing thus a way to reconcile PLT with the competing Dilution account. Overall, the model presents a novel account for explaining PLT effects on the basis of the low-level competitive interactions among neurons that represent visual input and the top-down signals that modulate neural activity. The implications of the model concerning the debate on the locus of selective attention as well as the origins of distractor interference in visual displays of varying load are discussed. PMID- 26858670 TI - The Florence Nightingale Effect: Organizational Identification Explains the Peculiar Link Between Others' Suffering and Workplace Functioning in the Homelessness Sector. AB - Frontline employees in the helping professions often perform their duties against a difficult backdrop, including a complex client base and ongoing themes of crisis, suffering, and distress. These factors combine to create an environment in which workers are vulnerable to workplace stress and burnout. The present study tested two models to understand how frontline workers in the homelessness sector deal with the suffering of their clients. First, we examined whether relationships between suffering and workplace functioning (job satisfaction and burnout) would be mediated by organizational identification. Second, we examined whether emotional distance from clients (i.e., infrahumanization, measured as reduced attribution of secondary emotions) would predict improved workplace functioning (less burnout and greater job satisfaction), particularly when client contact is high. The study involved a mixed-methods design comprising interview (N = 26) and cross-sectional survey data (N = 60) with a sample of frontline staff working in the homelessness sector. Participants were asked to rate the level of client suffering and attribute emotions in a hypothetical client task, and to complete questionnaire measures of burnout, job satisfaction, and organizational identification. We found no relationships between secondary emotion attribution and burnout or satisfaction. Instead, we found that perceiving higher client suffering was linked with higher job satisfaction and lower burnout. Mediation analyses revealed a mediating role for identification, such that recognizing suffering predicted greater identification with the organization, which fully mediated the relationship between suffering and job satisfaction, and also between suffering and burnout. Qualitative analysis of interview data also resonated with this conceptualization. We introduce this novel finding as the 'Florence Nightingale effect'. With this sample drawn from the homelessness sector, we provide preliminary evidence for the proposition that recognizing others' suffering may serve to increase job satisfaction and reduce burnout - by galvanizing organizational identification. PMID- 26858671 TI - Social Network Analysis and Nutritional Behavior: An Integrated Modeling Approach. AB - Animals have evolved complex foraging strategies to obtain a nutritionally balanced diet and associated fitness benefits. Recent research combining state space models of nutritional geometry with agent-based models (ABMs), show how nutrient targeted foraging behavior can also influence animal social interactions, ultimately affecting collective dynamics and group structures. Here we demonstrate how social network analyses can be integrated into such a modeling framework and provide a practical analytical tool to compare experimental results with theory. We illustrate our approach by examining the case of nutritionally mediated dominance hierarchies. First we show how nutritionally explicit ABMs that simulate the emergence of dominance hierarchies can be used to generate social networks. Importantly the structural properties of our simulated networks bear similarities to dominance networks of real animals (where conflicts are not always directly related to nutrition). Finally, we demonstrate how metrics from social network analyses can be used to predict the fitness of agents in these simulated competitive environments. Our results highlight the potential importance of nutritional mechanisms in shaping dominance interactions in a wide range of social and ecological contexts. Nutrition likely influences social interactions in many species, and yet a theoretical framework for exploring these effects is currently lacking. Combining social network analyses with computational models from nutritional ecology may bridge this divide, representing a pragmatic approach for generating theoretical predictions for nutritional experiments. PMID- 26858672 TI - Rapid Naming in Brazilian Students with Dyslexia and Attention Deficit Hyperactivity Disorder. AB - INTRODUCTION: The effective development of reading and writing skills requires the concerted action of several abilities, one of which is phonological processing. One of the main components of phonological processing is rapid automatized naming (RAN)-the ability to identify and recognize a given item by the activation and concomitant articulation of its name. OBJECTIVE: To assess the RAN performance of schoolchildren with dyslexia and attention deficit hyperactivity disorder (ADHD) compared with their peers. METHODS: In total, 70 schoolchildren aged between 8 and 11 years participated in the study. Of these, 16 children had a multiprofessional diagnosis of ADHD while 14 were diagnosed with dyslexia. Matched with these groups, 40 schoolchildren with no history of developmental impairments were also evaluated. The RAN test was administered to assess the length of time required to name a series of familiar visual stimuli. The statistical analysis was conducted using measures of descriptive statistics and the 2-sample t-test at the 5% significance level. RESULTS: The performance of the group with dyslexia was inferior to that of the control group in all tasks and the ADHD group had inferior performance for color and letters-naming tasks. The schoolchildren with dyslexia and those with ADHD showed very similar response times. Age was an important variable to be analyzed separately. As they aged, children with typical language development had fast answers on colors and digits tasks while children with dyslexia or ADHD did not show improvement with age. CONCLUSIONS: The schoolchildren with dyslexia took longer to complete all tasks and ADHD took longer to complete digits and objects tasks in comparison to their peers with typical development. This ability tended to improve with age, which was not the case, however, with schoolchildren who had ADHD or dyslexia. PMID- 26858673 TI - Predicting Individual Action Switching in Covert and Continuous Interactive Tasks Using the Fluid Events Model. AB - The Fluid Events Model is aimed at predicting changes in the actions people take on a moment-by-moment basis. In contrast with other research on action selection, this work does not investigate why some course of action was selected, but rather the likelihood of discontinuing the current course of action and selecting another in the near future. This is done using both task-based and experience based factors. Prior work evaluated this model in the context of trial-by-trial, independent, interactive events, such as choosing how to copy a figure of a line drawing. In this paper, we extend this model to more covert event experiences, such as reading narratives, as well as to continuous interactive events, such as playing a video game. To this end, the model was applied to existing data sets of reading time and event segmentation for written and picture stories. It was also applied to existing data sets of performance in a strategy board game, an aerial combat game, and a first person shooter game in which a participant's current state was dependent on prior events. The results revealed that the model predicted behavior changes well, taking into account both the theoretically defined structure of the described events, as well as a person's prior experience. Thus, theories of event cognition can benefit from efforts that take into account not only how events in the world are structured, but also how people experience those events. PMID- 26858674 TI - Filling the Silence: Reactivation, not Reconstruction. AB - In a self-paced reading experiment, we investigated the processing of sluicing constructions ("sluices") whose antecedent contained a known garden-path structure in German. Results showed decreased processing times for sluices with garden-path antecedents as well as a disadvantage for antecedents with non canonical word order downstream from the ellipsis site. A post-hoc analysis showed the garden-path advantage also to be present in the region right before the ellipsis site. While no existing account of ellipsis processing explicitly predicted the results, we argue that they are best captured by combining a local antecedent mismatch effect with memory trace reactivation through reanalysis. PMID- 26858675 TI - How to Make the Ghosts in my Bedroom Disappear? Focused-Attention Meditation Combined with Muscle Relaxation (MR Therapy)-A Direct Treatment Intervention for Sleep Paralysis. AB - Sleep paralysis (SP) is a common state of involuntary immobility occurring at sleep onset or offset. It can include terrifying hypnogogic or hypnopompic hallucinations of menacing bedroom intruders. Unsurprisingly, the experience is associated with great fear and horror worldwide. To date, there exist no direct treatment intervention for SP. In this article, I propose for the first time a type of focused inward-attention meditation combined with muscle relaxation as a direct intervention to be applied during the attack, to ameliorate and possibly eliminate it (what could be called, meditation-relaxation or MR therapy for SP). The intervention includes four steps: (1) reappraisal of the meaning of the attack; (2) psychological and emotional distancing; (3) inward focused-attention meditation; (4) muscle relaxation. The intervention promotes attentional shift away from unpleasant external and internal stimuli (i.e., terrifying hallucinations and bodily paralysis sensations) unto an emotionally pleasant internal object (e.g., a positive memory). It may facilitate a relaxed meditative state characterized by a shift from sympathetic to parasympathetic dominance, associated with greater levels of alpha activity (which may lead to drowsiness and potentially sleep). The procedure may also reduce the initial panic and arousal that occur when realizing one is paralyzed. In addition, I present a novel Panic-Hallucination (PH) Model of Sleep Paralysis; describing how through escalating cycles of fear and panic-like autonomic arousal, a positive feedback loop is created that worsens the attack (e.g., leading to longer and more fearful episodes), drives content of hallucinations, and causes future episodes of SP. Case examples are presented to illustrate the feasibility of MR therapy for SP. PMID- 26858676 TI - Quadratic Models May Provide a Useful Set of Models that Detect Combined Effects of Achievement Goals on Academic Attainment. PMID- 26858677 TI - Lay Definitions of Happiness across Nations: The Primacy of Inner Harmony and Relational Connectedness. AB - In well-being research the term happiness is often used as synonymous with life satisfaction. However, little is known about lay people's understanding of happiness. Building on the available literature, this study explored lay definitions of happiness across nations and cultural dimensions, analyzing their components and relationship with participants' demographic features. Participants were 2799 adults (age range = 30-60, 50% women) living in urban areas of Argentina, Brazil, Croatia, Hungary, India, Italy, Mexico, New Zealand, Norway, Portugal, South Africa, and United States. They completed the Eudaimonic and Hedonic Happiness Investigation (EHHI), reporting, among other information, their own definition of happiness. Answers comprised definitions referring to a broad range of life domains, covering both the contextual-social sphere and the psychological sphere. Across countries and with little variation by age and gender, inner harmony predominated among psychological definitions, and family and social relationships among contextual definitions. Whereas relationships are widely acknowledged as basic happiness components, inner harmony is substantially neglected. Nevertheless, its cross-national primacy, together with relations, is consistent with the view of an ontological interconnectedness characterizing living systems, shared by several conceptual frameworks across disciplines and cultures. At the methodological level, these findings suggest the potential of a bottom-up, mixed method approach to contextualize psychological dimensions within culture and lay understanding. PMID- 26858678 TI - Incrementality in Planning of Speech During Speaking and Reading Aloud: Evidence from Eye-Tracking. AB - Speaking is an incremental process where planning and articulation interleave. While incrementality has been studied in reading and online speech production separately, it has not been directly compared within one investigation. This study set out to compare the extent of planning incrementality in online sentence formulation versus reading aloud and how discourse context may constrain the planning scope of utterance preparation differently in these two modes of speech planning. Two eye-tracking experiments are reported: participants either described pictures of transitive events (Experiment 1) or read aloud the written descriptions of those events (Experiment 2). In both experiments, the information status of an object character was manipulated in the discourse preceding each picture or sentence. In the Literal condition, participants heard a story where object character was literally mentioned (e.g., fly). In the No Mention condition, stories did not literally mention nor prime the object character depicted on the picture or written in the sentence. The target response was expected to have the same structure and content in all conditions (The frog catches the fly). During naming, the results showed shorter speech onset latencies in the Literal condition than in the No Mention condition. However, no significant differences in gaze durations were found. In contrast, during reading, there were no significant differences in speech onset latencies but there were significantly longer gaze durations to the target picture/word in the Literal than in the No Mention condition. Our results shot that planning is more incremental during reading than during naming and that discourse context can be helpful during speaker but may hinder during reading aloud. Taken together our results suggest that on-line planning of response is affected by both linguistic and non-linguistic factors. PMID- 26858680 TI - Divided Attention and Processes Underlying Sense of Agency. AB - Sense of agency refers to the subjective feeling of controlling events through one's behavior or will. Sense of agency results from matching predictions of one's own actions with actual feedback regarding the action. Furthermore, when an action involves a cued goal, performance-based inference contributes to sense of agency. That is, if people achieve their goal, they would believe themselves to be in control. Previous studies have shown that both action-effect comparison and performance-based inference contribute to sense of agency; however, the dominance of one process over the other may shift based on task conditions such as the presence or absence of specific goals. In this study, we examined the influence of divided attention on these two processes underlying sense of agency in two conditions. In the experimental task, participants continuously controlled a moving dot for 10 s while maintaining a string of three or seven digits in working memory. We found that when there was no cued goal (no-cued-goal condition), sense of agency was impaired by high cognitive load. Contrastingly, when participants controlled the dot based on a cued goal (cued-goal-directed condition), their sense of agency was lower than in the no-cued-goal condition and was not affected by cognitive load. The results suggest that the action effect comparison process underlying sense of agency requires attention. On the other hand, the weaker influence of divided attention in the cued-goal-directed condition could be attributed to the dominance of performance-based inference, which is probably automatic. PMID- 26858681 TI - A Dissociation Between Recognition and Hedonic Value in Caloric and Non-caloric Carbonated Soft Drinks. AB - Consumption of sugar-sweetened beverages (SSBs) is considered to be a contributor to diabetes and the epidemic of obesity in many countries. The popularity of non caloric carbonated soft drinks as an alternative to SSBs may be a factor in reducing the health risks associated with SSBs consumption. This study focuses on the perceptual discrimination of SSBs from artificially sweetened beverages (ASBs). Fifty-five college students rated 14 commercially available carbonated soft drinks in terms of sweetness and likeability. They were also asked to recognize, if the drinks contained sugar or a non-caloric artificial sweetener. Overall, participants showed poor accuracy in discriminating drinks' sweeteners, with significantly lower accuracy for SSBs than ASBs. Interestingly, we found a dissociation between sweetener recognition and drink pleasantness. In fact, in spite of a chance-level discrimination accuracy of SSBs, their taste was systematically preferred to the taste of non-caloric beverages. Our findings support the idea that hedonic value of carbonated soft drinks is dissociable from its identification and that the activation of the pleasure system seems not to require explicit recognition of the sweetener contained in the soft drink. We hypothesize that preference for carbonated soft drinks containing sugar over non caloric alternatives might be modulated by metabolic factors that are independent from conscious and rational consumers' choices. PMID- 26858679 TI - Differences in Speech Recognition Between Children with Attention Deficits and Typically Developed Children Disappear When Exposed to 65 dB of Auditory Noise. AB - The most common neuropsychiatric condition in the in children is attention deficit hyperactivity disorder (ADHD), affecting ~6-9% of the population. ADHD is distinguished by inattention and hyperactive, impulsive behaviors as well as poor performance in various cognitive tasks often leading to failures at school. Sensory and perceptual dysfunctions have also been noticed. Prior research has mainly focused on limitations in executive functioning where differences are often explained by deficits in pre-frontal cortex activation. Less notice has been given to sensory perception and subcortical functioning in ADHD. Recent research has shown that children with ADHD diagnosis have a deviant auditory brain stem response compared to healthy controls. The aim of the present study was to investigate if the speech recognition threshold differs between attentive and children with ADHD symptoms in two environmental sound conditions, with and without external noise. Previous research has namely shown that children with attention deficits can benefit from white noise exposure during cognitive tasks and here we investigate if noise benefit is present during an auditory perceptual task. For this purpose we used a modified Hagerman's speech recognition test where children with and without attention deficits performed a binaural speech recognition task to assess the speech recognition threshold in no noise and noise conditions (65 dB). Results showed that the inattentive group displayed a higher speech recognition threshold than typically developed children and that the difference in speech recognition threshold disappeared when exposed to noise at supra threshold level. From this we conclude that inattention can partly be explained by sensory perceptual limitations that can possibly be ameliorated through noise exposure. PMID- 26858683 TI - Always on My Mind? Recognition of Attractive Faces May Not Depend on Attention. AB - Little research has examined what happens to attention and memory as a whole when humans see someone attractive. Hence, we investigated whether attractive stimuli gather more attention and are better remembered than unattractive stimuli. Participants took part in an attention task - in which matrices containing attractive and unattractive male naturalistic photographs were presented to 54 females, and measures of eye-gaze location and fixation duration using an eye tracker were taken - followed by a recognition task. Eye-gaze was higher for the attractive stimuli compared to unattractive stimuli. Also, attractive photographs produced more hits and false recognitions than unattractive photographs which may indicate that regardless of attention allocation, attractive photographs produce more correct but also more false recognitions. We present an evolutionary explanation for this, as attending to more attractive faces but not always remembering them accurately and differentially compared with unseen attractive faces, may help females secure mates with higher reproductive value. PMID- 26858684 TI - Macrocognition: From Theory to Toolbox. AB - We trace several trajectories-the evolution of field-based decision making models in the mid-1980s to the formation of the Naturalistic Decision Making movement in 1989, then the further broadening of NDM into Macrocognition in 2003, and finally the transition from macrocognitive models into a set of methods and tools to boost cognitive performance. PMID- 26858682 TI - Observational Learning: Tell Beginners What They Are about to Watch and They Will Learn Better. AB - Observation aids motor skill learning. When multiple models or different levels of performance are observed, does learning improve when the observer is informed of the performance quality prior to each observation trial or after each trial? We used a knock-down barrier task and asked participants to learn a new relative timing pattern that differed from that naturally emerging from the task constraints (Blandin et al., 1999). Following a physical execution pre-test, the participants observed two models demonstrating different levels of performance and were either informed of this performance prior to or after each observation trial. The results of the physical execution retention tests of the two experiments reported in the present study indicated that informing the observers of the demonstration quality they were about to see aided learning more than when this information was provided after each observation trial. Our results suggest that providing advanced information concerning the quality of the observation may help participants detect errors in the model's performance, which is something that novice participants have difficulty doing, and then learn from these observations. PMID- 26858685 TI - A Neurophysiological Investigation of Non-native Phoneme Perception by Dutch and German Listeners. AB - The Mismatch Negativity (MMN) response has often been used to measure memory traces for phonological representations and to show effects of long-term native language (L1) experience on neural organization. We know little about whether phonological representations of non-native (L2) phonemes are modulated by experience with distinct non-native accents. We used MMN to examine effects of experience with L2-accented speech on auditory brain responses. Specifically, we tested whether it is long-term experience with language-specific L2 pronunciations or instead acoustic similarity between L2 speech sounds that modulates non-native phoneme perception. We registered MMN responses of Dutch and German proficient L2 speakers of English to the English interdental fricative /??/ and compared it to its non-native pronunciations /s/ (typical pronunciation of /??/ for German speakers) and /t/ (typical pronunciation of /??/ for Dutch speakers). Dutch and German listeners heard the English pseudoword thond and its pronunciation deviants sond and tond. We computed the identity Mismatch Negativity (iMMN) by analyzing the difference in ERPs when the deviants were the frequent vs. the infrequent stimulus for the respective group of L2 listeners. For both groups, tond and sond elicited mismatch effects of comparable size. Overall, the results suggest that experience with deviant pronunciations of L2 speech sounds in foreign-accented speech does not alter auditory memory traces. Instead, non-native phoneme perception seems to be modulated by acoustic similarity between speech sounds rather than by experience with typical L2 pronunciation patterns. PMID- 26858691 TI - Dynamics of a Mathematical Model for Tuberculosis with Variability in Susceptibility and Disease Progressions Due to Difference in Awareness Level. AB - This work extends a mathematical model for the transmission dynamics of tuberculosis that examined the impact of certain factors on tuberculosis case detection (Okuonghae and Omosigho, 2011). The extended model now classifies the latently infected individuals by their level of tuberculosis awareness (as was done for the susceptible sub-population) and further expands the number of key factors that can positively affect the tuberculosis case detection rate. The effect of these identified factors on the associated reproduction number of the model is considered. It is shown that the system can undergo the phenomenon of backward bifurcation when the associated reproduction number of the model is less than unity; in a special case, the effect of exogenous re-infection on the backward bifurcation phenomenon is significantly dictated by the level of awareness of the latently infected individuals. Qualitative and quantitative analysis of the model showed the effect of key identified factors on the dynamics of tuberculosis while suggesting a serious concentration on tuberculosis awareness programmes, active case finding strategies and use of active cough identification for identifying likely TB cases and sustaining awareness campaigns over a long period of time. PMID- 26858688 TI - The "TSH Receptor Glo Assay" - A High-Throughput Detection System for Thyroid Stimulation. AB - BACKGROUND: To identify novel small molecules against the TSH receptor, we developed a sensitive transcription-based luciferase high-throughput screening (HTS) system named the TSHR-Glo Assay (TSHR-Glo). METHODS: This assay uses double transfected Chinese hamster ovary cells stably expressing the human TSHR and a cAMP-response element (CRE) construct fused to an improved luciferase reporter gene. RESULTS: The assay was highly responsive toward TSH in a dose-dependent manner with a TSH sensitivity of 10(-10)M (10 +/- 1.12 MUU/ml) and thyroid stimulating antibodies, a hallmark of Graves' disease, could also be detected. The assay was validated against the standard indicator of HTS performance - the Z factor (Z') - producing a score of 0.895. Using the TSHR-Glo assay, we screened 48,224 compounds from a diverse chemical library in duplicate plates at a fixed dose of 17 MUM. Twenty molecules with the greatest activity out of 62 molecules that were identified by this technique were subsequently screened against the parent luciferase stable cell line in order to eliminate false positive stimulators. CONCLUSION: Using this approach, we were able to identify specific agonists against the TSH receptor leading to the characterization of several TSH agonist molecules. Hence, the TSHR-Glo assay was a one-step cell-based HTS assay, which was successful in the discovery of novel small molecular agonists and for the detection of stimulating antibodies to the TSH receptor. PMID- 26858687 TI - IGF-Binding Proteins in Type-1 Diabetes Are More Severely Altered in the Presence of Complications. AB - AIMS: Reduced levels of free and total insulin-like growth factor 1 (IGF-I) have been observed in type-1 diabetes (T1D) patients. The bioavailability of IGF-I from the circulation to the target cells is controlled by multifunctional IGF binding proteins (IGFBPs). The aim of this study was to profile serum IGFBPs in T1D and its complications. DESIGN: We measured the IGFBP levels in 3662 patient serum samples from our ongoing Phenome and Genome of Diabetes Autoimmunity (PAGODA) study. IGFBP levels of four different groups of T1D patients (with 0, 1, 2, and >=3 complications) were compared with healthy controls. RESULTS: Three serum IGFBPs (IGFBP-1, -2, and -6) are significantly higher in T1D patients, and these alterations are greater in the presence of diabetic complications. IGFBP-3 is lower in patients with diabetic complications. Analyses using quintiles revealed that risk of T1D complications increases with increasing concentrations of IGFBP-2 (fifth quintile ORs: 18-60, p < 10(-26)), IGFBP-1 (fifth quintile ORs: 8-20, p < 10(-15)), and IGFBP-6 (fifth quintile ORs: 3-148, p < 10(-3)). IGFBP-3 has a negative association with T1D complications (fifth quintile ORs: 0.12-0.25, p < 10(-5)). CONCLUSION: We found that elevated serum levels of IGFBP-1, -2, and 6 were associated with T1D, and its complications and IGFBP-3 level was found to be decreased in T1D with complications. Given the known role of these IGFBPs, the overall impact of these alterations suggests a negative effect on IGF signaling. PMID- 26858689 TI - Differential Effects of Camel Milk on Insulin Receptor Signaling - Toward Understanding the Insulin-Like Properties of Camel Milk. AB - Previous studies on the Arabian camel (Camelus dromedarius) showed beneficial effects of its milk reported in diverse models of human diseases, including a substantial hypoglycemic activity. However, the cellular and molecular mechanisms involved in such effects remain completely unknown. In this study, we hypothesized that camel milk may act at the level of human insulin receptor (hIR) and its related intracellular signaling pathways. Therefore, we examined the effect of camel milk on the activation of hIR transiently expressed in human embryonic kidney 293 (HEK293) cells using bioluminescence resonance energy transfer (BRET) technology. BRET was used to assess, in live cells and real-time, the physical interaction between hIR and insulin receptor signaling proteins (IRS1) and the growth factor receptor-bound protein 2 (Grb2). Our data showed that camel milk did not promote any increase in the BRET signal between hIR and IRS1 or Grb2 in the absence of insulin stimulation. However, it significantly potentiated the maximal insulin-promoted BRET signal between hIR and Grb2 but not IRS1. Interestingly, camel milk appears to differentially impact the downstream signaling since it significantly activated ERK1/2 and potentiated the insulin induced ERK1/2 but not Akt activation. These observations are to some extent consistent with the BRET data since ERK1/2 and Akt activation are known to reflect the engagement of Grb2 and IRS1 pathways, respectively. The preliminary fractionation of camel milk suggests the peptide/protein nature of the active component in camel milk. Together, our study demonstrates for the first time an allosteric effect of camel milk on insulin receptor conformation and activation with differential effects on its intracellular signaling. These findings should help to shed more light on the hypoglycemic activity of camel milk with potential therapeutic applications. PMID- 26858690 TI - Bacterioplankton Dynamics within a Large Anthropogenically Impacted Urban Estuary. AB - The abundant and diverse microorganisms that inhabit aquatic systems are both determinants and indicators of aquatic health, providing essential ecosystem services such as nutrient cycling but also causing harmful blooms and disease in impacted habitats. Estuaries are among the most urbanized coastal ecosystems and as a consequence experience substantial environmental pressures, providing ideal systems to study the influence of anthropogenic inputs on microbial ecology. Here we use the highly urbanized Sydney Harbor, Australia, as a model system to investigate shifts in microbial community composition and function along natural and anthopogenic physicochemical gradients, driven by stormwater inflows, tidal flushing and the input of contaminants and both naturally and anthropogenically derived nutrients. Using a combination of amplicon sequencing of the 16S rRNA gene and shotgun metagenomics, we observed strong patterns in microbial biogeography across the estuary during two periods: one of high and another of low rainfall. These patterns were driven by shifts in nutrient concentration and dissolved oxygen leading to a partitioning of microbial community composition in different areas of the harbor with different nutrient regimes. Patterns in bacterial composition were related to shifts in the abundance of Rhodobacteraceae, Flavobacteriaceae, Microbacteriaceae, Halomonadaceae, Acidomicrobiales, and Synechococcus, coupled to an enrichment of total microbial metabolic pathways including phosphorus and nitrogen metabolism, sulfate reduction, virulence, and the degradation of hydrocarbons. Additionally, community beta-diversity was partitioned between the two sampling periods. This potentially reflected the influence of shifting allochtonous nutrient inputs on microbial communities and highlighted the temporally dynamic nature of the system. Combined, our results provide insights into the simultaneous influence of natural and anthropogenic drivers on the structure and function of microbial communities within a highly urbanized aquatic ecosystem. PMID- 26858692 TI - Actinobacteria from Arid and Desert Habitats: Diversity and Biological Activity. AB - The lack of new antibiotics in the pharmaceutical pipeline guides more and more researchers to leave the classical isolation procedures and to look in special niches and ecosystems. Bioprospecting of extremophilic Actinobacteria through mining untapped strains and avoiding resiolation of known biomolecules is among the most promising strategies for this purpose. With this approach, members of acidtolerant, alkalitolerant, psychrotolerant, thermotolerant, halotolerant and xerotolerant Actinobacteria have been obtained from respective habitats. Among these, little survey exists on the diversity of Actinobacteria in arid areas, which are often adapted to relatively high temperatures, salt concentrations, and radiation. Therefore, arid and desert habitats are special ecosystems which can be recruited for the isolation of uncommon Actinobacteria with new metabolic capability. At the time of this writing, members of Streptomyces, Micromonospora, Saccharothrix, Streptosporangium, Cellulomonas, Amycolatopsis, Geodermatophilus, Lechevalieria, Nocardia, and Actinomadura are reported from arid habitats. However, metagenomic data present dominant members of the communities in desiccating condition of areas with limited water availability that are not yet isolated. Furthermore, significant diverse types of polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) genes are detected in xerophilic and xerotolerant Actinobacteria and some bioactive compounds are reported from them. Rather than pharmaceutically active metabolites, molecules with protection activity against drying such as Ectoin and Hydroxyectoin with potential application in industry and agriculture have also been identified from xerophilic Actinobacteria. In addition, numerous biologically active small molecules are expected to be discovered from arid adapted Actinobacteria in the future. In the current survey, the diversity and biotechnological potential of Actinobacteria obtained from arid ecosystems, along with the recent work trend on Iranian arid soils, are reported. PMID- 26858686 TI - Microglial Cells as a Link between Cannabinoids and the Immune Hypothesis of Psychiatric Disorders. AB - Psychiatric disorders are one of the leading causes of disability worldwide. Although several therapeutic options are available, the exact mechanisms responsible for the genesis of these disorders remain to be fully elucidated. In the last decade, a body of evidence has supported the involvement of the immune system in the pathophysiology of these conditions. Microglial cells play a significant role in maintaining brain homeostasis and surveillance. Dysregulation of microglial functions has been associated with several psychiatric conditions. Cannabinoids regulate the brain-immune axis and inhibit microglial cell activation. Here, we summarized evidence supporting the hypothesis that microglial cells could be a target for cannabinoid influence on psychiatric disorders, such as anxiety, depression, schizophrenia, and stress-related disorders. PMID- 26858694 TI - Chaperonin GroEL/GroES Over-Expression Promotes Aminoglycoside Resistance and Reduces Drug Susceptibilities in Escherichia coli Following Exposure to Sublethal Aminoglycoside Doses. AB - Antibiotic resistance is an increasing challenge to modern healthcare. Aminoglycoside antibiotics cause translation corruption and protein misfolding and aggregation in Escherichia coli. We previously showed that chaperonin GroEL/GroES depletion and over-expression sensitize and promote short-term tolerance, respectively, to this drug class. Here, we show that chaperonin GroEL/GroES over-expression accelerates acquisition of streptomycin resistance and reduces susceptibility to several other antibiotics following sub-lethal streptomycin antibiotic exposure. Chaperonin buffering could provide a novel mechanism for emergence of antibiotic resistance. PMID- 26858695 TI - Carbon Material Optimized Biocathode for Improving Microbial Fuel Cell Performance. AB - To improve the performance of microbial fuel cells (MFCs), the biocathode electrode material of double-chamber was optimized. Alongside the basic carbon fiber brush, three carbon materials namely graphite granules, activated carbon granules (ACG) and activated carbon powder, were added to the cathode-chambers to improve power generation. The result shows that the addition of carbon materials increased the amount of available electroactive microbes on the electrode surface and thus promote oxygen reduction rate, which improved the generation performance of the MFCs. The Output current (external resistance = 1000 Omega) greatly increased after addition of the three carbon materials and maximum power densities in current stable phase increased by 47.4, 166.1, and 33.5%, respectively. Additionally, coulombic efficiencies of the MFC increased by 16.3, 64.3, and 20.1%, respectively. These results show that MFC when optimized with ACG show better power generation, higher chemical oxygen demands removal rate and coulombic efficiency. PMID- 26858693 TI - A Fluorescent Bioreporter for Acetophenone and 1-Phenylethanol derived from a Specifically Induced Catabolic Operon. AB - The beta-proteobacterium Aromatoleum aromaticum degrades the aromatic ketone acetophenone, a key intermediate of anaerobic ethylbenzene metabolism, either aerobically or anaerobically via a complex ATP-dependent acetophenone carboxylase and a benzoylacetate-CoA ligase. The genes coding for these enzymes (apcABCDE and bal) are organized in an apparent operon and are expressed in the presence of the substrate acetophenone. To study the conditions under which this operon is expressed in more detail, we constructed a reporter strain by inserting a gene fusion of apcA, the first gene of the apc-bal operon, with the gene for the fluorescent protein mCherry into the chromosome of A. aromaticum. The fusion protein indeed accumulated consistently with the expression pattern of the acetophenone-metabolic enzymes under various growth conditions. After evaluating and quantifying the data by fluorescence microscopy, fluorescence-based flow cytometry and immunoblot analysis, mCherry production was found to be proportional to the applied acetophenone concentrations. The reporter strain allowed quantification of acetophenone within a concentration range of 50 MUM (detection limit) to 250 MUM after 12 and 24 h. Moreover, production of the Apc mCherry fusion protein in the reporter strain was highly specific and responded to acetophenone and both enantiomers of 1-phenylethanol, which are easily converted to acetophenone. Other analogous substrates showed either a significantly weaker response or none at all. Therefore, the reporter strain provides a basis for the development of a specific bioreporter system for acetophenone with an application potential reaching from environmental monitoring to petroleum prospecting. PMID- 26858697 TI - Hydrogen Utilization Potential in Subsurface Sediments. AB - Subsurface microbial communities undertake many terminal electron-accepting processes, often simultaneously. Using a tritium-based assay, we measured the potential hydrogen oxidation catalyzed by hydrogenase enzymes in several subsurface sedimentary environments (Lake Van, Barents Sea, Equatorial Pacific, and Gulf of Mexico) with different predominant electron-acceptors. Hydrogenases constitute a diverse family of enzymes expressed by microorganisms that utilize molecular hydrogen as a metabolic substrate, product, or intermediate. The assay reveals the potential for utilizing molecular hydrogen and allows qualitative detection of microbial activity irrespective of the predominant electron accepting process. Because the method only requires samples frozen immediately after recovery, the assay can be used for identifying microbial activity in subsurface ecosystems without the need to preserve live material. We measured potential hydrogen oxidation rates in all samples from multiple depths at several sites that collectively span a wide range of environmental conditions and biogeochemical zones. Potential activity normalized to total cell abundance ranges over five orders of magnitude and varies, dependent upon the predominant terminal electron acceptor. Lowest per-cell potential rates characterize the zone of nitrate reduction and highest per-cell potential rates occur in the methanogenic zone. Possible reasons for this relationship to predominant electron acceptor include (i) increasing importance of fermentation in successively deeper biogeochemical zones and (ii) adaptation of H2ases to successively higher concentrations of H2 in successively deeper zones. PMID- 26858696 TI - Modulation of Type III Secretion System in Pseudomonas aeruginosa: Involvement of the PA4857 Gene Product. AB - Pseudomonas aeruginosa is an opportunistic pathogen that causes serious acute or chronic infections in humans. Acute infections typically involve the type III secretion systems (T3SSs) and bacterial motility, whereas chronic infections are often associated with biofilm formation and the type VI secretion system. To identify new genes required for pathogenesis, a transposon mutagenesis library was constructed and the gene PA4857, named tspR, was found to modulate T3SS gene expression. Deletion of P. aeruginosa tspR reduced the virulence in a mouse acute lung infection model and diminished cytotoxicity. Suppression of T3SS gene expression in the tspR mutant resulted from compromised translation of the T3SS master regulator ExsA. TspR negatively regulated two small RNAs, RsmY and RsmZ, which control RsmA. Our data demonstrated that defects in T3SS expression and biofilm formation in retS mutant could be partially restored by overexpression of tspR. Taken together, our results demonstrated that the newly identified retS tspR pathway is coordinated with the retS-gacS system, which regulates the genes associated with acute and chronic infections and controls the lifestyle choice of P. aeruginosa. PMID- 26858698 TI - Microbial Communities in Methane- and Short Chain Alkane-Rich Hydrothermal Sediments of Guaymas Basin. AB - The hydrothermal sediments of Guaymas Basin, an active spreading center in the Gulf of California (Mexico), are rich in porewater methane, short-chain alkanes, sulfate and sulfide, and provide a model system to explore habitat preferences of microorganisms, including sulfate-dependent, methane- and short chain alkane oxidizing microbial communities. In this study, hot sediments (above 60 degrees C) covered with sulfur-oxidizing microbial mats surrounding a hydrothermal mound (termed "Mat Mound") were characterized by porewater geochemistry of methane, C2 C6 short-chain alkanes, sulfate, sulfide, sulfate reduction rate measurements, in situ temperature gradients, bacterial and archaeal 16S rRNA gene clone libraries and V6 tag pyrosequencing. The most abundantly detected groups in the Mat mound sediments include anaerobic methane-oxidizing archaea of the ANME-1 lineage and its sister clade ANME-1Guaymas, the uncultured bacterial groups SEEP-SRB2 within the Deltaproteobacteria and the separately branching HotSeep-1 Group; these uncultured bacteria are candidates for sulfate-reducing alkane oxidation and for sulfate-reducing syntrophy with ANME archaea. The archaeal dataset indicates distinct habitat preferences for ANME-1, ANME-1-Guaymas, and ANME-2 archaea in Guaymas Basin hydrothermal sediments. The bacterial groups SEEP-SRB2 and HotSeep 1 co-occur with ANME-1 and ANME-1Guaymas in hydrothermally active sediments underneath microbial mats in Guaymas Basin. We propose the working hypothesis that this mixed bacterial and archaeal community catalyzes the oxidation of both methane and short-chain alkanes, and constitutes a microbial community signature that is characteristic for hydrothermal and/or cold seep sediments containing both substrates. PMID- 26858699 TI - The Use of Germinants to Potentiate the Sensitivity of Bacillus anthracis Spores to Peracetic Acid. AB - Elimination of Bacillus anthracis spores from the environment is a difficult and costly process due in part to the toxicity of current sporicidal agents. For this reason we investigated the ability of the spore germinants L-alanine (100 mM) and inosine (5 mM) to reduce the concentration of peracetic acid (PAA) required to inactivate B. anthracis spores. While L-alanine significantly enhanced (p = 0.0085) the bactericidal activity of 500 ppm PAA the same was not true for inosine suggesting some form of negative interaction. In contrast the germinant combination proved most effective at 100 ppm PAA (p = 0.0009). To determine if we could achieve similar results in soil we treated soil collected from the burial site of an anthrax infected animal which had been supplemented with spores of the Sterne strain of B. anthracis to increase the level of contamination to 10(4) spores/g. Treatment with germinants followed 1 h later by 5000 ppm PAA eliminated all of the spores. In contrast direct treatment of the animal burial site using this approach delivered using a back pack sprayer had no detectable effect on the level of B. anthracis contamination or on total culturable bacterial numbers over the course of the experiment. It did trigger a significant, but temporary, reduction (p < 0.0001) in the total spore count suggesting that germination had been triggered under real world conditions. In conclusion, we have shown that the application of germinants increase the sensitivity of bacterial spores to PAA. While the results of the single field trial were inconclusive, the study highlighted the potential of this approach and the challenges faced when attempting to perform real world studies on B. anthracis spores contaminated sites. PMID- 26858700 TI - Development of a Sterne-Based Complement Fixation Test to Monitor the Humoral Response Induced by Anthrax Vaccines. AB - Anthrax is a zoonotic disease caused by Bacillus anthracis spore-forming bacterium. Since it is primarily a disease of animals, the control in animals, and humans depend on the prevention in livestock, principally cattle, sheep, and goats. Most veterinary vaccines utilize the toxigenic, uncapsulated (pXO1+/pXO2-) B. anthracis strain 34F2 which affords protection through the production of neutralizing antibodies directed to the toxin components Protective Antigen (PA), Lethal Factor (LF), and Edema Factor (EF). The titration of specific antibodies in sera of vaccinated animals is crucial to evaluate the efficacy of the vaccination and to obtain epidemiological information for an effective anthrax surveillance. In this study, we developed a Sterne-based Complement Fixation Test (CFT) to detect specific antibodies induced in animals vaccinated with Sterne 34F2. We assessed its efficacy in laboratory animals and under field conditions by monitoring the humoral response induced by vaccination in cattle. The results indicated that the Sterne-based CFT is able to correctly identify vaccinated animals. It proved to be a very sensitive and specific test. Moreover, the Sterne based CFT offers many benefits with regard to costs, standardization and reproducibility of the assay procedure. PMID- 26858701 TI - Classification of Extrapulmonary Manifestations Due to Mycoplasma pneumoniae Infection on the Basis of Possible Pathogenesis. AB - The list of extrapulmonary manifestations due to Mycoplasma pneumoniae infection can be classified according to the following three possible mechanisms derived from the established biological activity of M. pneumoniae; (1) a direct type in which the bacterium is present at the site of inflammation and local inflammatory cytokines induced by the bacterium play an important role (2) an indirect type in which the bacterium is not present at the site of inflammation and immune modulations, such as autoimmunity or formation of immune complexes, play an important role, and (3) a vascular occlusion type in which obstruction of blood flow induced either directly or indirectly by the bacterium plays an important role. Recent studies concerning extrapulmonary manifestations have prompted the author to upgrade the list, including cardiac and aortic thrombi as cardiovascular manifestations; erythema nodosum, cutaneous leukocytoclastic vasculitis, and subcorneal pustular dermatosis as dermatological manifestations; acute cerebellar ataxia, opsoclonus-myoclonus syndrome, and thalamic necrosis as neurological manifestations; pulmonary embolism as a respiratory system manifestation; and renal artery embolism as a urogenital tract manifestation. Continuing nosological confusion on M. pneumoniae-induced mucositis (without skin lesions), which may be called M. pneumoniae-associated mucositis or M. pneumoniae induced rash and mucositis separately from Stevens-Johnson syndrome, is argued in the dermatological manifestations. Serological methods are recommended for diagnosis because pneumonia or respiratory symptoms are often minimal or even absent in extrapulmonary manifestations due to M. pneumoniae infection. Concomitant use of immunomodulators, such as corticosteroids or immunoglobulins with antibiotics effective against M. pneumoniae, can be considered as treatment modalities for most severe cases, such as encephalitis. Further studies would be necessary to construct a comprehensive therapeutic strategy, covering microbiology (antibiotics), immunology (immunomodulators), and hematology (anticoagulants). The possible influence of the emergence of macrolide-resistant M. pneumoniae on extrapulmonary manifestations, which can be considered of limited clinical threat in Japan where the resistant rate has currently decreased, is discussed on the basis of unique biological characteristics of M. pneumoniae, the smallest self-replicating organism. PMID- 26858703 TI - High-Throughput Isolation of Giant Viruses in Liquid Medium Using Automated Flow Cytometry and Fluorescence Staining. AB - The isolation of giant viruses using amoeba co-culture is tedious and fastidious. Recently, the procedure was successfully associated with a method that detects amoebal lysis on agar plates. However, the procedure remains time-consuming and is limited to protozoa growing on agar. We present here advances for the isolation of giant viruses. A high-throughput automated method based on flow cytometry and fluorescent staining was used to detect the presence of giant viruses in liquid medium. Development was carried out with the Acanthamoeba polyphaga strain widely used in past and current co-culture experiments. The proof of concept was validated with virus suspensions: artificially contaminated samples but also environmental samples from which viruses were previously isolated. After validating the technique, and fortuitously isolating a new Mimivirus, we automated the technique on 96-well plates and tested it on clinical and environmental samples using other protozoa. This allowed us to detect more than 10 strains of previously known species of giant viruses and seven new strains of a new virus lineage. This automated high-throughput method demonstrated significant time saving, and higher sensitivity than older techniques. It thus creates the means to isolate giant viruses at high speed. PMID- 26858702 TI - Analysis of the First Temperate Broad Host Range Brucellaphage (BiPBO1) Isolated from B. inopinata. AB - Brucella species are important human and animal pathogens. Though, only little is known about mobile genetic elements of these highly pathogenic bacteria. To date, neither plasmids nor temperate phages have been described in brucellae. We analyzed genomic sequences of various reference and type strains and identified a number of putative prophages residing within the Brucella chromosomes. By induction, phage BiPBO1 was isolated from Brucella inopinata. BiPBO1 is a siphovirus that infects several Brucella species including Brucella abortus and Brucella melitensis. Integration of the phage genome occurs adjacent to a tRNA gene in chromosome 1 (chr 1). The bacterial (attB) and phage (attP) attachment sites comprise an identical sequence of 46 bp. This sequence exists in many Brucella and Ochrobactrum species. The BiPBO1 genome is composed of a 46,877 bp double-stranded DNA. Eighty-seven putative gene products were determined, of which 32 could be functionally assigned. Strongest similarities were found to a temperate phage residing in the chromosome of Ochrobactrum anthropi ATCC 49188 and to prophages identified in several families belonging to the order rhizobiales. The data suggest that horizontal gene transfer may occur between Brucella and Ochrobactrum and underpin the close relationship of these environmental and pathogenic bacteria. PMID- 26858704 TI - Prodigiosin Induces Autolysins in Actively Grown Bacillus subtilis Cells. AB - Prodigiosin produced by marine bacterium Vibrio ruber DSM 14379 exhibits a potent antimicrobial activity against a broad range of Gram positive and Gram negative bacteria. The mechanism of prodigiosin antimicrobial action, however, is not known. In this work, the effect of prodigiosin on Bacillus subtilis growth, cell membrane leakage, and induction of autolysins was studied. Treating B. subtilis with prodigiosin resulted in rapid decline of optical density and increased cell membrane leakage measured by beta-galactosidase activity. Cell lysis was initiated immediately after treatment with prodigiosin in the middle exponential phase and was completed within 2 h. Lytic activity of prodigiosin in mutant strains with impaired autolysin genes lytABCD decreased for 80% compared to the wild type strain, while in lytABCDEF mutant strain prodigiosin had no bacteriolytic but only bacteriostatic effect. Fast prodigiosin lytic activity on individual B. subtilis cells was confirmed by a modified comet assay. The results indicate that prodigiosin autolysin induction in B. subtilis is growth phase dependent. PMID- 26858705 TI - Metagenomic Analysis Indicates Epsilonproteobacteria as a Potential Cause of Microbial Corrosion in Pipelines Injected with Bisulfite. AB - Sodium bisulfite (SBS) is used as an oxygen scavenger to decrease corrosion in pipelines transporting brackish subsurface water used in the production of bitumen by steam-assisted gravity drainage. Sequencing 16S rRNA gene amplicons has indicated that SBS addition increased the fraction of the sulfate-reducing bacteria (SRB) Desulfomicrobium, as well as of Desulfocapsa, which can also grow by disproportionating sulfite into sulfide, sulfur, and sulfate. SRB use cathodic H2, formed by reduction of aqueous protons at the iron surface, or use low potential electrons from iron and aqueous protons directly for sulfate reduction. In order to reveal the effects of SBS treatment in more detail, metagenomic analysis was performed with pipe-associated solids (PAS) scraped from a pipe section upstream (PAS-616P) and downstream (PAS-821TP) of the SBS injection point. A major SBS-induced change in microbial community composition and in affiliated hynL genes for the large subunit of [NiFe] hydrogenase was the appearance of sulfur-metabolizing Epsilonproteobacteria of the genera Sulfuricurvum and Sulfurovum. These are chemolithotrophs, which oxidize sulfide or sulfur with O2 or reduce sulfur with H2. Because O2 was absent, this class likely catalyzed reduction of sulfur (S(0)) originating from the metabolism of bisulfite with cathodic H2 (or low potential electrons and aqueous protons) originating from the corrosion of steel (Fe(0)). Overall this accelerates reaction of of S(0) and Fe(0) to form FeS, making this class a potentially powerful contributor to microbial corrosion. The PAS-821TP metagenome also had increased fractions of Deltaproteobacteria including the SRB Desulfomicrobium and Desulfocapsa. Altogether, SBS increased the fraction of hydrogen-utilizing Delta- and Epsilonproteobacteria in brackish-water-transporting pipelines, potentially stimulating anaerobic pipeline corrosion if dosed in excess of the intended oxygen scavenger function. PMID- 26858706 TI - Heterologous Production of an Energy-Conserving Carbon Monoxide Dehydrogenase Complex in the Hyperthermophile Pyrococcus furiosus. AB - Carbon monoxide (CO) is an important intermediate in anaerobic carbon fixation pathways in acetogenesis and methanogenesis. In addition, some anaerobes can utilize CO as an energy source. In the hyperthermophilic archaeon Thermococcus onnurineus, which grows optimally at 80 degrees C, CO oxidation and energy conservation is accomplished by a respiratory complex encoded by a 16-gene cluster containing a CO dehydrogenase, a membrane-bound [NiFe]-hydrogenase and a Na(+)/H(+) antiporter module. This complex oxidizes CO, evolves CO2 and H2, and generates a Na(+) motive force that is used to conserve energy by a Na(+) dependent ATP synthase. Herein we used a bacterial artificial chromosome to insert the 13.2 kb gene cluster encoding the CO-oxidizing respiratory complex of T. onnurineus into the genome of the heterotrophic archaeon, Pyrococcus furiosus, which grows optimally at 100 degrees C. P. furiosus is normally unable to utilize CO, however, the recombinant strain readily oxidized CO and generated H2 at 80 degrees C. Moreover, CO also served as an energy source and allowed the P. furiosus strain to grow with a limiting concentration of sugar or with peptides as the carbon source. Moreover, CO oxidation by P. furiosus was also coupled to the re-utilization, presumably for biosynthesis, of acetate generated by fermentation. The functional transfer of CO utilization between Thermococcus and Pyrococcus species demonstrated herein is representative of the horizontal gene transfer of an environmentally relevant metabolic capability. The transfer of CO utilizing, hydrogen-producing genetic modules also has applications for biohydrogen production and a CO-based industrial platform for various thermophilic organisms. PMID- 26858707 TI - Current Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus in Elderly French People: Troublesome Clones on the Horizon. AB - OBJECTIVE: In 2015, we conducted at 44 healthcare facilities (HCFs) and 21 nursing homes (NHs) a 3-month bloodstream infection (BSI) survey, and a 1-day prevalence study to determine the rate of carriage of methicillin-resistant Staphylococcus aureus (MRSA) in 891 patients and 470 residents. We investigated the molecular characteristics of the BSI-associated and colonizing MRSA isolates, and assessed cross-transmission using double-locus sequence typing and pulsed field gel electrophoresis protocol. RESULTS: The incidence of MRSA-BSI was 0.040/1000 patient-days (19 cases). The prevalence of MRSA carriage was 4.2% in patients (n = 39) and 8.7% in residents (n = 41) (p < 0.001). BSI-associated and colonizing isolates were similar: none were PVL-positive; 86.9% belonged to clonal complexes 5 and 8; 93.9% were resistant to fluoroquinolones. The qacA/B gene was carried by 15.8% of the BSI-associated isolates [3/3 BSI cases in intensive care units (ICUs)], and 7.7% of the colonizing isolates in HCFs. Probable resident-to-resident transmission was identified in four NHs. CONCLUSION: Despite generally reassuring results, we identified two key concerns. First, a worryingly high prevalence of the qacA/B gene in MRSA isolates. Antisepsis measures being crucial to prevent healthcare-associated infections, our findings raise questions about the potential risk associated with chlorhexidine use in qacA/B(+) MRSA carriers, particularly in ICUs. Second, NHs are a weak link in MRSA control. MRSA spread was not controlled at several NHs; because of their frequent contact with the community, conditions are favorable for these NHs to serve as reservoirs of USA300 clone for local HCFs. PMID- 26858708 TI - Identification of Key Amino Acid Residues Modulating Intracellular and In vitro Microcin E492 Amyloid Formation. AB - Microcin E492 (MccE492) is a pore-forming bacteriocin produced and exported by Klebsiella pneumoniae RYC492. Besides its antibacterial activity, excreted MccE492 can form amyloid fibrils in vivo as well as in vitro. It has been proposed that bacterial amyloids can be functional playing a biological role, and in the particular case of MccE492 it would control the antibacterial activity. MccE492 amyloid fibril's morphology and formation kinetics in vitro have been well-characterized, however, it is not known which amino acid residues determine its amyloidogenic propensity, nor if it forms intracellular amyloid inclusions as has been reported for other bacterial amyloids. In this work we found the conditions in which MccE492 forms intracellular amyloids in Escherichia coli cells, that were visualized as round-shaped inclusion bodies recognized by two amyloidophilic probes, 2-4'-methylaminophenyl benzothiazole and thioflavin-S. We used this property to perform a flow cytometry-based assay to evaluate the aggregation propensity of MccE492 mutants, that were designed using an in silico prediction of putative aggregation hotspots. We established that the predicted amino acid residues 54-63, effectively act as a pro-amyloidogenic stretch. As in the case of other amyloidogenic proteins, this region presented two gatekeeper residues (P57 and P59), which disfavor both intracellular and in vitro MccE492 amyloid formation, preventing an uncontrolled aggregation. Mutants in each of these gatekeeper residues showed faster in vitro aggregation and bactericidal inactivation kinetics, and the two mutants were accumulated as dense amyloid inclusions in more than 80% of E. coli cells expressing these variants. In contrast, the MccE492 mutant lacking residues 54-63 showed a significantly lower intracellular aggregation propensity and slower in vitro polymerization kinetics. Electron microscopy analysis of the amyloids formed in vitro by these mutants revealed that, although with different efficiency, all formed fibrils morphologically similar to wild-type MccE492. The physiological implication of MccE492 intracellular amyloid formation is probably similar to the inactivation process observed for extracellular amyloids, and could be used as a mean of sequestering potentially toxic species inside the cell when this bacteriocin is produced in large amounts. PMID- 26858709 TI - Temperature-Dependent Gentamicin Resistance of Francisella tularensis is Mediated by Uptake Modulation. AB - Gentamicin (Gm) is an aminoglycoside commonly used to treat bacterial infections such as tularemia - the disease caused by Francisella tularensis. In addition to being pathogenic, F. tularensis is found in environmental niches such as soil where this bacterium likely encounters Gm producers (Micromonospora sp.). Here we show that F. tularensis exhibits increased resistance to Gm at ambient temperature (26 degrees C) compared to mammalian body temperature (37 degrees C). To evaluate whether F. tularensis was less permeable to Gm at 26 degrees C, a fluorescent marker [Texas Red (Tr)] was conjugated with Gm, yielding Tr-Gm. Bacteria incubated at 26 degrees C showed reduced fluorescence compared to those at 37 degrees C when exposed to Tr-Gm suggesting that uptake of Gm was reduced at 26 degrees C. Unconjugated Gm competitively inhibited uptake of Tr-Gm, demonstrating that this fluorescent compound was taken up similarly to unconjugated Gm. Lysates of F. tularensis bacteria incubated with Gm at 37 degrees C inhibited the growth of Escherichia coli significantly more than lysates from bacteria incubated at 26 degrees C, further indicating reduced uptake at this lower temperature. Other facultative pathogens (Listeria monocytogenes and Klebsiella pneumoniae) exhibited increased resistance to Gm at 26 degrees C suggesting that the results generated using F. tularensis may be generalizable to diverse bacteria. Regulation of the uptake of antibiotics provides a mechanism by which facultative pathogens survive alongside antibiotic producing microbes in nature. PMID- 26858710 TI - Biodegradation, Biosorption of Phenanthrene and Its Trans-Membrane Transport by Massilia sp. WF1 and Phanerochaete chrysosporium. AB - Reducing phenanthrene (PHE) in the environment is critical to ecosystem and human health. Biodegradation, biosorption, and the trans-membrane transport mechanism of PHE by a novel strain, Massilia sp. WF1, and an extensively researched model fungus, Phanerochaete chrysosporium were investigated in aqueous solutions. Results showed that the PHE residual concentration decreased with incubation time and the data fitted well to a first-order kinetic equation, and the t 1/2 of PHE degradation by WF1, spores, and mycelial pellets of P. chrysosporium were about 2 h, 87 days, and 87 days, respectively. The biosorbed PHE was higher in P. Chrysosporium than that in WF1, and it increased after microorganisms were inactivated and inhibited, especially in mycelial pellets. The detected intracellular auto-fluorescence of PHE by two-photon excitation microscopy also proved that PHE indeed entered into the cells. Based on regression, the intracellular (K din) and extracellular (K dout) dissipation rate constants of PHE by WF1 were higher than those by spores and mycelial pellets. In addition, the transport rate constant of PHE from outside solution into cells (KinS/Vout ) for WF1 were higher than the efflux rate constant of PHE from cells to outside solution (KoutS/Vin ), while the opposite phenomena were observed for spores and mycelial pellets. The amount of PHE that transported from outside solution into cells was attributed to the rapid degradation and active PHE efflux in the cells of WF1 and P. Chrysosporium, respectively. Besides, the results under the inhibition treatments of 4 degrees C, and the presence of sodium azide, colchicine, and cytochalasin B demonstrated that a passive trans-membrane transport mechanism was involved in PHE entering into the cells of WF1 and P. Chrysosporium. PMID- 26858711 TI - Antibody Response to Mycoplasma pneumoniae: Protection of Host and Influence on Outbreaks? AB - In humans of all ages, the cell wall-less and genome-reduced species Mycoplasma pneumoniae can cause infections of the upper and lower respiratory tract. The well-documented occurrence of major peaks in the incidence of community-acquired pneumonia cases reported world-wide, the multifaceted clinical manifestations of infection and the increasing number of resistant strains provide reasons for ongoing interest in the pathogenesis of mycoplasmal disease. The results of recent studies have provided insights into the interaction of the limited virulence factors of the bacterium with its host. In addition, the availability of complete M. pneumoniae genomes from patient isolates and the development of proteomic methods for investigation of mycoplasmas have not only allowed characterization of sequence divergences between strains but have also shown the importance of proteins and protein parts for induction of the immune reaction after infection. This review focuses on selected aspects of the humoral host immune response as a factor that might influence the clinical course of infections, subsequent protection in cases of re-infections and changes of epidemiological pattern of infections. The characterization of antibodies directed to defined antigens and approaches to promote their induction in the respiratory mucosa are also preconditions for the development of a vaccine to protect risk populations from severe disease due to M. pneumoniae. PMID- 26858712 TI - The Global Reciprocal Reprogramming between Mycobacteriophage SWU1 and Mycobacterium Reveals the Molecular Strategy of Subversion and Promotion of Phage Infection. AB - Bacteriophages are the viruses of bacteria, which have contributed extensively to our understanding of life and modern biology. The phage-mediated bacterial growth inhibition represents immense untapped source for novel antimicrobials. Insights into the interaction between mycobacteriophage and Mycobacterium host will inform better utilizing of mycobacteriophage. In this study, RNA sequencing technology (RNA-seq) was used to explore the global response of Mycobacterium smegmatis mc(2)155 at an early phase of infection with mycobacteriophage SWU1, key host metabolic processes of M. smegmatis mc(2)155 shut off by SWU1, and the responsible phage proteins. The results of RNA-seq were confirmed by Real-time PCR and functional assay. 1174 genes of M. smegmatis mc(2)155 (16.9% of the entire encoding capacity) were differentially regulated by phage infection. These genes belong to six functional categories: (i) signal transduction, (ii) cell energetics, (iii) cell wall biosynthesis, (iv) DNA, RNA, and protein biosynthesis, (v) iron uptake, (vi) central metabolism. The transcription patterns of phage SWU1 were also characterized. This study provided the first global glimpse of the reciprocal reprogramming between the mycobacteriophage and Mycobacterium host. PMID- 26858713 TI - A Novel PCR-Based Approach for Accurate Identification of Vibrio parahaemolyticus. AB - A PCR-based assay was developed for more accurate identification of Vibrio parahaemolyticus through targeting the bla CARB-17 like element, an intrinsic beta-lactamase gene that may also be regarded as a novel species-specific genetic marker of this organism. Homologous analysis showed that bla CARB-17 like genes were more conservative than the tlh, toxR and atpA genes, the genetic markers commonly used as detection targets in identification of V. parahaemolyticus. Our data showed that this bla CARB-17-specific PCR-based detection approach consistently achieved 100% specificity, whereas PCR targeting the tlh and atpA genes occasionally produced false positive results. Furthermore, a positive result of this test is consistently associated with an intrinsic ampicillin resistance phenotype of the test organism, presumably conferred by the products of bla CARB-17 like genes. We envision that combined analysis of the unique genetic and phenotypic characteristics conferred by bla CARB-17 shall further enhance the detection specificity of this novel yet easy-to-use detection approach to a level superior to the conventional methods used in V. parahaemolyticus detection and identification. PMID- 26858714 TI - Ethanol Production by Selected Intestinal Microorganisms and Lactic Acid Bacteria Growing under Different Nutritional Conditions. AB - To gain some specific insight into the roles microorganisms might play in non alcoholic fatty liver disease (NAFLD), some intestinal and lactic acid bacteria and one yeast (Anaerostipes caccae, Bacteroides thetaiotaomicron, Bifidobacterium longum, Enterococcus fecalis, Escherichia coli, Lactobacillus acidophilus, Lactobacillus fermentum, Lactobacillus plantarum, Weissella confusa, Saccharomyces cerevisiae) were characterized by high performance liquid chromatography for production of ethanol when grown on different carbohydrates: hexoses (glucose and fructose), pentoses (arabinose and ribose), disaccharides (lactose and lactulose), and inulin. Highest amounts of ethanol were produced by S. cerevisiae, L. fermentum, and W. confusa on glucose and by S. cerevisiae and W. confusa on fructose. Due to mannitol-dehydrogenase expressed in L. fermentum, ethanol production on fructose was significantly (P < 0.05) reduced. Pyruvate and citrate, two potential electron acceptors for regeneration of NAD(+)/NADP(+), drastically reduced ethanol production with acetate produced instead in L. fermentum grown on glucose and W. confusa grown on glucose and fructose, respectively. In fecal slurries prepared from feces of four overweight volunteers, ethanol was found to be produced upon addition of fructose. Addition of A. caccae, L. acidophilus, L. fermentum, as well as citrate and pyruvate, respectively, abolished ethanol production. However, addition of W. confusa resulted in significantly (P < 0.05) increased production of ethanol. These results indicate that microorganisms like W. confusa, a hetero-fermentative, mannitol-dehydrogenase negative lactic acid bacterium, may promote NAFLD through ethanol produced from sugar fermentation, while other intestinal bacteria and homo- and hetero-fermentative but mannitol-dehydrogenase positive lactic acid bacteria may not promote NAFLD. Also, our studies indicate that dietary factors interfering with gastrointestinal microbiota and microbial metabolism may be important in preventing or promoting NAFLD. PMID- 26858715 TI - Macrophage Migration Inhibitory Factor in Clinical Kidney Disease. AB - Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine implicated in acute and chronic inflammatory conditions, including sepsis, autoimmune disease, atherogenesis, plaque instability, and pulmonary arterial hypertension. MIF in plasma and urine is significantly elevated in patients with acute kidney injury (AKI) and elevated MIF in serum is associated with markers of oxidative stress, endothelial dysfunction, arterial stiffness, and markers of myocardial damage in chronic kidney disease (CKD). Furthermore, MIF seems to be involved in vascular processes and cardiovascular disease associated with CKD, glomerulonephritis, autosomal dominant polycystic kidney disease, and possibly also in progression to renal failure. Moreover, in active anti-neutrophil cytoplasmatic antibody-associated vasculitis, plasma MIF levels have been shown to be significantly elevated as compared with samples from patients in remission. A significant difference in the genotype frequency of high production MIF -173 G/C genotype has been found in end-stage renal disease, compared to controls. Inhibition of MIF in a diabetic nephropathy model ameliorated blood glucose and albuminuria and in a model of adult polycystic kidney disease cyst growth was delayed. Preclinical studies support a potential therapeutic role for MIF in AKI and in a number of CKDs, whereas these data in human disease are still observational. Future interventional studies are needed to delineate the role of MIF as a treatment target in clinical kidney disease. PMID- 26858717 TI - Major Histocompatibility Complex and Malaria: Focus on Plasmodium vivax Infection. AB - The importance of host and parasite genetic factors in malaria resistance or susceptibility has been investigated since the middle of the last century. Nowadays, of all diseases that affect man, malaria still plays one of the highest levels of selective pressure on human genome. Susceptibility to malaria depends on exposure profile, epidemiological characteristics, and several components of the innate and adaptive immune system that influences the quality of the immune response generated during the Plasmodium lifecycle in the vertebrate host. But it is well known that the parasite's enormous capacity of genetic variation in conjunction with the host genetics polymorphism is also associated with a wide spectrum of susceptibility degrees to complicated or severe forms of the disease. In this scenario, variations in genes of the major histocompatibility complex (MHC) associated with host resistance or susceptibility to malaria have been identified and used as markers in host-pathogen interaction studies, mainly those evaluating the impact on the immune response, acquisition of resistance, or increased susceptibility to infection or vulnerability to disease. However, due to the intense selective pressure, number of cases, and mortality rates, the majority of the reported associations reported concerned Plasmodium falciparum malaria. Studies on the MHC polymorphism and its association with Plasmodium vivax, which is the most widespread Plasmodium and the most prevalent species outside the African continent, are less frequent but equally important. Despite punctual contributions, there are accumulated evidences of human genetic control in P. vivax infection and disease. Herein, we review the current knowledge in the field of MHC and derived molecules (HLA Class I, Class II, TNF-alpha, LTA, BAT1, and CTL4) regarding P. vivax malaria. We discuss particularly the results of P. vivax studies on HLA class I and II polymorphisms in relation to host susceptibility, naturally acquired immune response against specific antigens and the implication of this knowledge to overcome the parasite immune evasion. Finally, the potential impact of such polymorphisms on the development of vaccine candidate antigens against P. vivax will be studied. PMID- 26858718 TI - The Emerging Roles of Gamma-Delta T Cells in Tissue Inflammation in Experimental Autoimmune Encephalomyelitis. AB - gammadelta (gamma-delta) T cells, a small population of unconventional T cells, have been found in central nervous system lesions of multiple sclerosis (MS) patients, but their function in disease activity is not clearly understood. Previous studies in experimental autoimmune encephalomyelitis (EAE) were inconsistent in identifying their specific roles in suppressing or promoting disease pathogenesis. Emerging advancements in the biology of gammadelta T cells especially in the context of their being the major initial producers of IL-17, suggested their crucial role in pathogenesis of EAE. In addition, gammadelta T cells express high levels of IL-23R and IL-1R, which further enhance their effector functions in the pathogenesis of EAE. Nonetheless, activated heterogeneous gammadelta T cells display functional dichotomy, which is crucial in determining the outcomes of tissue inflammation in EAE. In this review, we discussed recent advances in understanding the biology of gammadelta T cells in tissue inflammation as well as their roles in suppressing or promoting the development of EAE. PMID- 26858716 TI - Animal Models for HIV Cure Research. AB - The HIV-1/AIDS pandemic continues to spread unabated worldwide, and no vaccine exists within our grasp. Effective antiretroviral therapy (ART) has been developed, but ART cannot clear the virus from the infected patient. A cure for HIV-1 is badly needed to stop both the spread of the virus in human populations and disease progression in infected individuals. A safe and effective cure strategy for human immunodeficiency virus (HIV) infection will require multiple tools, and appropriate animal models are tools that are central to cure research. An ideal animal model should recapitulate the essential aspects of HIV pathogenesis and associated immune responses, while permitting invasive studies, thus allowing a thorough evaluation of strategies aimed at reducing the size of the reservoir (functional cure) or eliminating the reservoir altogether (sterilizing cure). Since there is no perfect animal model for cure research, multiple models have been tailored and tested to address specific quintessential questions of virus persistence and eradication. The development of new non-human primate and mouse models, along with a certain interest in the feline model, has the potential to fuel cure research. In this review, we highlight the major animal models currently utilized for cure research and the contributions of each model to this goal. PMID- 26858720 TI - Myeloid Extracellular Vesicles: Messengers from the Demented Brain. AB - Blood-borne monocyte derived cells play a pivotal, initially unrecognized, role in most central nervous system disorders, including diseases initially classified as purely neurodegenerative (i.e., Alzheimer's disease, Parkinson's disease, and ALS). Their trafficking to the brain and spinal cord has been extensively studied in classical neuroinflammatory disorders such as multiple sclerosis. Central nervous system resident myeloid cells, namely microglia and perivascular macrophages, also are in the spotlight of investigations on neurological disorders. Myeloid cells, such as infiltrating macrophages and microglia, have been described as having both protective and destructive features in neurological disorders, thus identification of their functional phenotype during disease evolution would be of paramount importance. Extracellular vesicles, namely exosomes and shed vesicles, are released by virtually any cell type and can be detected and identified in terms of cell origin in biological fluids. They therefore constitute an ideal tool to access information on cells residing in an inaccessible site such as the brain. We will review here available information on extracellular vesicles detection in neurological disorders with special emphasis on neurodegenerative diseases. PMID- 26858719 TI - Prospective Clinical Testing of Regulatory Dendritic Cells in Organ Transplantation. AB - Dendritic cells (DC) are rare, professional antigen-presenting cells with ability to induce or regulate alloimmune responses. Regulatory DC (DCreg) with potential to down-modulate acute and chronic inflammatory conditions that occur in organ transplantation can be generated in vitro under a variety of conditions. Here, we provide a rationale for evaluation of DCreg therapy in clinical organ transplantation with the goal of promoting sustained, donor-specific hyporesponsiveness, while lowering the incidence and severity of rejection and reducing patients' dependence on anti-rejection drugs. Generation of donor- or recipient-derived DCreg that suppress T cell responses and prolong transplant survival in rodents or non-human primates has been well-described. Recently, good manufacturing practice (GMP)-grade DCreg have been produced at our Institution for prospective use in human organ transplantation. We briefly review experience of regulatory immune therapy in organ transplantation and describe our experience generating and characterizing human monocyte-derived DCreg. We propose a phase I/II safety study in which the influence of donor-derived DCreg combined with conventional immunosuppression on subclinical and clinical rejection and host alloimmune responses will be examined in detail. PMID- 26858721 TI - Comparative Anatomy of Phagocytic and Immunological Synapses. AB - The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all critical features to build functional phagosomes and immunological synapses. Interestingly, both phagocytic cups and immunological synapses display particular spatial and temporal patterns of receptors and signaling molecules, leading to the notion of "phagocytic synapse." Here, we discuss both types of structures, their organization, and the mechanisms by which they are generated and regulated. PMID- 26858722 TI - Natural Killer Cells and Liver Fibrosis. AB - In the 40 years since the discovery of natural killer (NK) cells, it has been well established that these innate lymphocytes are important for early and effective immune responses against transformed cells and infections with different pathogens. In addition to these classical functions of NK cells, we now know that they are part of a larger family of innate lymphoid cells and that they can even mediate memory-like responses. Additionally, tissue-resident NK cells with distinct phenotypical and functional characteristics have been identified. Here, we focus on the phenotype of different NK cell subpopulations that can be found in the liver and summarize the current knowledge about the functional role of these cells with a special emphasis on liver fibrosis. NK cell cytotoxicity can contribute to liver damage in different forms of liver disease. However, NK cells can limit liver fibrosis by killing hepatic stellate cell-derived myofibroblasts, which play a key role in this pathogenic process. Therefore, liver NK cells need to be tightly regulated in order to balance these beneficial and pathological effects. PMID- 26858723 TI - Sequencing, De novo Assembly, Functional Annotation and Analysis of Phyllanthus amarus Leaf Transcriptome Using the Illumina Platform. AB - Phyllanthus amarus Schum. and Thonn., a widely distributed annual medicinal herb has a long history of use in the traditional system of medicine for over 2000 years. However, the lack of genomic data for P. amarus, a non-model organism hinders research at the molecular level. In the present study, high-throughput sequencing technology has been employed to enhance better understanding of this herb and provide comprehensive genomic information for future work. Here P. amarus leaf transcriptome was sequenced using the Illumina Miseq platform. We assembled 85,927 non-redundant (nr) "unitranscript" sequences with an average length of 1548 bp, from 18,060,997 raw reads. Sequence similarity analyses and annotation of these unitranscripts were performed against databases like green plants nr protein database, Gene Ontology (GO), Clusters of Orthologous Groups (COG), PlnTFDB, KEGG databases. As a result, 69,394 GO terms, 583 enzyme codes (EC), 134 KEGG maps, and 59 Transcription Factor (TF) families were generated. Functional and comparative analyses of assembled unitranscripts were also performed with the most closely related species like Populus trichocarpa and Ricinus communis using TRAPID. KEGG analysis showed that a number of assembled unitranscripts were involved in secondary metabolites, mainly phenylpropanoid, flavonoid, terpenoids, alkaloids, and lignan biosynthetic pathways that have significant medicinal attributes. Further, Fragments Per Kilobase of transcript per Million mapped reads (FPKM) values of the identified secondary metabolite pathway genes were determined and Reverse Transcription PCR (RT-PCR) of a few of these genes were performed to validate the de novo assembled leaf transcriptome dataset. In addition 65,273 simple sequence repeats (SSRs) were also identified. To the best of our knowledge, this is the first transcriptomic dataset of P. amarus till date. Our study provides the largest genetic resource that will lead to drug development and pave the way in deciphering various secondary metabolite biosynthetic pathways in P. amarus, especially those conferring the medicinal attributes of this potent herb. PMID- 26858724 TI - Primary and Secondary Abscission in Pisum sativum and Euphorbia pulcherrima-How Do They Compare and How Do They Differ? AB - Abscission is a highly regulated and coordinated developmental process in plants. It is important to understand the processes leading up to the event, in order to better control abscission in crop plants. This has the potential to reduce yield losses in the field and increase the ornamental value of flowers and potted plants. A reliable method of abscission induction in poinsettia (Euphorbia pulcherrima) flowers has been established to study the process in a comprehensive manner. By correctly decapitating buds of the third order, abscission can be induced in 1 week. AFLP differential display (DD) was used to search for genes regulating abscission. Through validation using qRT-PCR, more information of the genes involved during induced secondary abscission have been obtained. A study using two pea (Pisum sativum) mutants in the def (Developmental funiculus) gene, which was compared with wild type peas (tall and dwarf in both cases) was performed. The def mutant results in a deformed, abscission-less zone instead of normal primary abscission at the funiculus. RNA in situ hybridization studies using gene sequences from the poinsettia differential display, resulted in six genes differentially expressed for abscission specific genes in both poinsettia and pea. Two of these genes are associated with gene up- or down-regulation during the first 2 days after decapitation in poinsettia. Present and previous results in poinsettia (biochemically and gene expressions), enables a more detailed division of the secondary abscission phases in poinsettia than what has previously been described from primary abscission in Arabidopsis. This study compares the inducible secondary abscission in poinsettia and the non-abscising mutants/wild types in pea demonstrating primary abscission zones. The results may have wide implications on the understanding of abscission, since pea and poinsettia have been separated for 94-98 million years in evolution, hence any genes or processes in common are bound to be widespread in the plant kingdom. PMID- 26858725 TI - 14-3-3 Proteins in Guard Cell Signaling. AB - Guard cells are specialized cells located at the leaf surface delimiting pores which control gas exchanges between the plant and the atmosphere. To optimize the CO2 uptake necessary for photosynthesis while minimizing water loss, guard cells integrate environmental signals to adjust stomatal aperture. The size of the stomatal pore is regulated by movements of the guard cells driven by variations in their volume and turgor. As guard cells perceive and transduce a wide array of environmental cues, they provide an ideal system to elucidate early events of plant signaling. Reversible protein phosphorylation events are known to play a crucial role in the regulation of stomatal movements. However, in some cases, phosphorylation alone is not sufficient to achieve complete protein regulation, but is necessary to mediate the binding of interactors that modulate protein function. Among the phosphopeptide-binding proteins, the 14-3-3 proteins are the best characterized in plants. The 14-3-3s are found as multiple isoforms in eukaryotes and have been shown to be involved in the regulation of stomatal movements. In this review, we describe the current knowledge about 14-3-3 roles in the regulation of their binding partners in guard cells: receptors, ion pumps, channels, protein kinases, and some of their substrates. Regulation of these targets by 14-3-3 proteins is discussed and related to their function in guard cells during stomatal movements in response to abiotic or biotic stresses. PMID- 26858727 TI - Organ-Specific Quantitative Genetics and Candidate Genes of Phenylpropanoid Metabolism in Brassica oleracea. AB - Phenolic compounds are proving to be increasingly important for human health and in crop development, defense and adaptation. In spite of the economical importance of Brassica crops in agriculture, the mechanisms involved in the biosynthesis of phenolic compounds presents in these species remain unknown. The genetic and metabolic basis of phenolics accumulation was dissected through analysis of total phenolics concentration and its individual components in leaves, flower buds, and seeds of a double haploid (DH) mapping population of Brassica oleracea. The quantitative trait loci (QTL) that had an effect on phenolics concentration in each organ were integrated, resulting in 33 consensus QTLs controlling phenolics traits. Most of the studied compounds had organ specific genomic regulation. Moreover, this information allowed us to propose candidate genes and to predict the function of genes underlying the QTL. A number of previously unknown potential regulatory regions involved in phenylpropanoid metabolism were identified and this study illustrates how plant ontogeny can affect a biochemical pathway. PMID- 26858726 TI - Phenylpropanoids Accumulation in Eggplant Fruit: Characterization of Biosynthetic Genes and Regulation by a MYB Transcription Factor. AB - Phenylpropanoids are major secondary metabolites in eggplant (Solanum melongena) fruits. Chlorogenic acid (CGA) accounts for 70-90% of total phenolics in flesh tissues, while anthocyanins are mainly present in the fruit skin. As a contribution to the understanding of the peculiar accumulation of these health promoting metabolites in eggplant, we report on metabolite abundance, regulation of CGA and anthocyanin biosynthesis, and characterization of candidate CGA biosynthetic genes in S. melongena. Higher contents of CGA, Delphinidin 3 rutinoside, and rutin were found in eggplant fruits compared to other tissues, associated to an elevated transcript abundance of structural genes such as PAL, HQT, DFR, and ANS, suggesting that active in situ biosynthesis contributes to anthocyanin and CGA accumulation in fruit tissues. Putative orthologs of the two CGA biosynthetic genes PAL and HQT, as well as a variant of a MYB1 transcription factor showing identity with group six MYBs, were isolated from an Occidental S. melongena traditional variety and demonstrated to differ from published sequences from Asiatic varieties. In silico analysis of the isolated SmPAL1, SmHQT1, SmANS, and SmMyb1 promoters revealed the presence of several Myb regulatory elements for the biosynthetic genes and unique elements for the TF, suggesting its involvement in other physiological roles beside phenylpropanoid biosynthesis regulation. Transient overexpression in Nicotiana benthamiana leaves of SmMyb1 and of a C terminal SmMyb1 truncated form (SmMyb1Delta9) resulted in anthocyanin accumulation only of SmMyb1 agro-infiltrated leaves. A yeast two-hybrid assay confirmed the interaction of both SmMyb1 and SmMyb1Delta9 with an anthocyanin related potato bHLH1 TF. Interestingly, a doubled amount of CGA was detected in both SmMyb1 and SmMyb1Delta9 agro-infiltrated leaves, thus suggesting that the N terminal region of SmMyb1 is sufficient to activate its synthesis. These data suggest that a deletion of the C-terminal region of SmMyb1 does not limit its capability to regulate CGA accumulation, but impairs anthocyanin biosynthesis. To our knowledge, this is the first study reporting a functional elucidation of the role of the C-term conserved domain in MYB activator proteins. PMID- 26858728 TI - Endosomal Interactions during Root Hair Growth. AB - The dynamic localization of endosomal compartments labeled with targeted fluorescent protein tags is routinely followed by time lapse fluorescence microscopy approaches and single particle tracking algorithms. In this way trajectories of individual endosomes can be mapped and linked to physiological processes as cell growth. However, other aspects of dynamic behavior including endosomal interactions are difficult to follow in this manner. Therefore, we characterized the localization and dynamic properties of early and late endosomes throughout the entire course of root hair formation by means of spinning disc time lapse imaging and post-acquisition automated multitracking and quantitative analysis. Our results show differential motile behavior of early and late endosomes and interactions of late endosomes that may be specified to particular root hair domains. Detailed data analysis revealed a particular transient interaction between late endosomes-termed herein as dancing-endosomes-which is not concluding to vesicular fusion. Endosomes preferentially located in the root hair tip interacted as dancing-endosomes and traveled short distances during this interaction. Finally, sizes of early and late endosomes were addressed by means of super-resolution structured illumination microscopy (SIM) to corroborate measurements on the spinning disc. This is a first study providing quantitative microscopic data on dynamic spatio-temporal interactions of endosomes during root hair tip growth. PMID- 26858729 TI - In vitro Biochemical Characterization of All Barley Endosperm Starch Synthases. AB - Starch is the main storage polysaccharide in cereals and the major source of calories in the human diet. It is synthesized by a panel of enzymes including five classes of starch synthases (SSs). While the overall starch synthase (SS) reaction is known, the functional differences between the five SS classes are poorly understood. Much of our knowledge comes from analyzing mutant plants with altered SS activities, but the resulting data are often difficult to interpret as a result of pleitropic effects, competition between enzymes, overlaps in enzyme activity and disruption of multi-enzyme complexes. Here we provide a detailed biochemical study of the activity of all five classes of SSs in barley endosperm. Each enzyme was produced recombinantly in E. coli and the properties and modes of action in vitro were studied in isolation from other SSs and other substrate modifying activities. Our results define the mode of action of each SS class in unprecedented detail; we analyze their substrate selection, temperature dependence and stability, substrate affinity and temporal abundance during barley development. Our results are at variance with some generally accepted ideas about starch biosynthesis and might lead to the reinterpretation of results obtained in planta. In particular, they indicate that granule bound SS is capable of processive action even in the absence of a starch matrix, that SSI has no elongation limit, and that SSIV, believed to be critical for the initiation of starch granules, has maltoligosaccharides and not polysaccharides as its preferred substrates. PMID- 26858730 TI - Are We on the Right Track: Can Our Understanding of Abscission in Model Systems Promote or Derail Making Improvements in Less Studied Crops? AB - As the world population grows and resources and climate conditions change, crop improvement continues to be one of the most important challenges for agriculturalists. The yield and quality of many crops is affected by abscission or shattering, and environmental stresses often hasten or alter the abscission process. Understanding this process can not only lead to genetic improvement, but also changes in cultural practices and management that will contribute to higher yields, improved quality and greater sustainability. As plant scientists, we have learned significant amounts about this process through the study of model plants such as Arabidopsis, tomato, rice, and maize. While these model systems have provided significant valuable information, we are sometimes challenged to use this knowledge effectively as variables including the economic value of the crop, the uniformity of the crop, ploidy levels, flowering and crossing mechanisms, ethylene responses, cultural requirements, responses to changes in environment, and cellular and tissue specific morphological differences can significantly influence outcomes. The value of genomic resources for lesser-studied crops such as cranberries and grapes and the orphan crop fonio will also be considered. PMID- 26858732 TI - Enforced Clonality Confers a Fitness Advantage. AB - In largely clonal plants, splitting of a maternal plant into potentially independent plants (ramets) is usually spontaneous; however, such fragmentation also occurs in otherwise non-clonal species due to application of external force. This process might play an important yet largely overlooked role for otherwise non-clonal plants by providing a mechanism to regenerate after disturbance. Here, in a 5-year garden experiment on two short-lived, otherwise non-clonal species, Barbarea vulgaris and Barbarea stricta, we compared the fitness of plants fragmented by simulated disturbance ("enforced ramets") both with plants that contemporaneously originate in seed and with individuals unscathed by the disturbance event. Because the ability to regrow from fragments is related to plant age and stored reserves, we compared the effects of disturbance applied during three different ontogenetic stages of the plants. In B. vulgaris, enforced ramet fitness was higher than the measured fitness values of both uninjured plants and plants established from seed after the disturbance. This advantage decreased with increasing plant age at the time of fragmentation. In B. stricta, enforced ramet fitness was lower than or similar to fitness of uninjured plants and plants grown from seed. Our results likely reflect the habitat preferences of the study species, as B. vulgaris occurs in anthropogenic, disturbed habitats where body fragmentation is more probable and enforced clonality thus more advantageous than in the more natural habitats preferred by B. stricta. Generalizing from our results, we see that increased fitness yielded by enforced clonality would confer an evolutionary advantage in the face of disturbance, especially in habitats where a seed bank has not been formed, e.g., during invasion or colonization. Our results thus imply that enforced clonality should be taken into account when studying population dynamics and life strategies of otherwise non-clonal species in disturbed habitats. PMID- 26858731 TI - Proteomic Analyses Provide Novel Insights into Plant Growth and Ginsenoside Biosynthesis in Forest Cultivated Panax ginseng (F. Ginseng). AB - F. Ginseng (Panax ginseng) is planted in the forest to enhance the natural ginseng resources, which have an immense medicinal and economic value. The morphology of the cultivated plants becomes similar to that of wild growing ginseng (W. Ginseng) over the years. So far, there have been no studies highlighting the physiological or functional changes in F. Ginseng and its wild counterparts. In the present study, we used proteomic technologies (2DE and iTRAQ) coupled to mass spectrometry to compare W. Ginseng and F. Ginseng at various growth stages. Hierarchical cluster analysis based on protein abundance revealed that the protein expression profile of 25-year-old F. Ginseng was more like W. Ginseng than less 20-year-old F. Ginseng. We identified 192 differentially expressed protein spots in F. Ginseng. These protein spots increased with increase in growth years of F. Ginseng and were associated with proteins involved in energy metabolism, ginsenosides biosynthesis, and stress response. The mRNA, physiological, and metabolic analysis showed that the external morphology, protein expression profile, and ginsenoside synthesis ability of the F. Ginseng increased just like that of W. Ginseng with the increase in age. Our study represents the first characterization of the proteome of F. Ginseng during development and provides new insights into the metabolism and accumulation of ginsenosides. PMID- 26858733 TI - Physiological Characterization and Comparative Transcriptome Analysis of a Slow Growing Reduced-Thylakoid Mutant of Chinese Cabbage (Brassica campestris ssp. pekinensis). AB - Mutants are ideal for studying physiological processes. The leaves of Chinese cabbage are a major place for photosynthesis, and the mutation of these leaves may directly affect the rate of plant growth and development, thus influencing the formation of its leafy head. We characterized a slow-growing mutant, which was designated as drm. The drm exhibited slow growth and development at the seedling and heading stages, leading to the production of a tiny, leafy head, and chlorophyll-deficient leaves, especially in seedlings. Genetic analysis indicated that the phenotype of drm was controlled by a single recessive nuclear gene. Compared with the wild-type "FT" line, the drm's chlorophyll content was significantly reduced and its chloroplast structure was abnormal. Moreover, its photosynthetic efficiency and chlorophyll fluorescence parameters were significantly decreased. The changes in leaf color, combined with these altered physiological characters, may influence the growth and development of plant, ultimately resulting in the slow-growing phenotype. To further understand the molecular regulation mechanisms of phenotypic differences between "FT" and drm, comparative transcriptome analyses were performed using RNA-Seq; a total of 338 differentially expressed genes (DEGs) were detected between "FT" and drm. According to GO and KEGG pathway analysis, a number of DEGs involved in chlorophyll degradation and photosynthesis were identified, such as chlorophyllase and ribulose-1,5-bisphosphate carboxylase/oxygenase. In addition, the expression patterns of 12 DEGs, including three chlorophyll degradation- and photosynthesis-related genes and nine randomly-selected genes, were confirmed by qRT-PCR. Numerous single nucleotide polymorphisms were also identified, providing a valuable resource for research and molecular marker-assistant breeding in Chinese cabbage. These results contribute to our understanding of the molecular regulation mechanisms underlying growth and development and lay the foundation for future genetic and functional genomics in Chinese cabbage. PMID- 26858734 TI - Seed-Specific Expression of Spider Silk Protein Multimers Causes Long-Term Stability. AB - Seeds enable plants to germinate and to grow in situations of limited availability of nutrients. The stable storage of different seed proteins is a remarkable presumption for successful germination and growth. These strategies have been adapted and used in several molecular farming projects. In this study, we explore the benefits of seed-based expression to produce the high molecular weight spider silk protein FLAG using intein-based trans-splicing. Multimers larger than 460 kDa in size are routinely produced, which is above the native size of the FLAG protein. The storage of seeds for 8 weeks and 1 year at an ambient temperature of 15 degrees C does not influence the accumulation level. Even the extended storage time does not influence the typical pattern of multimerized bands. These results show that seeds are the method of choice for stable accumulation of products of complex transgenes and have the capability for long-term storage at moderate conditions, an important feature for the development of suitable downstream processes. PMID- 26858735 TI - Microarray Analysis of Rice d1 (RGA1) Mutant Reveals the Potential Role of G Protein Alpha Subunit in Regulating Multiple Abiotic Stresses Such as Drought, Salinity, Heat, and Cold. AB - The genome-wide role of heterotrimeric G-proteins in abiotic stress response in rice has not been examined from a functional genomics perspective, despite the availability of mutants and evidences involving individual genes/processes/stresses. Our rice whole transcriptome microarray analysis (GSE 20925 at NCBI GEO) using the G-alpha subunit (RGA1) null mutant (Daikoku 1 or d1) and its corresponding wild type (Oryza sativa Japonica Nipponbare) identified 2270 unique differentially expressed genes (DEGs). Out of them, we mined for all the potentially abiotic stress-responsive genes using Gene Ontology terms, STIFDB2.0 and Rice DB. The first two approaches produced smaller subsets of the 1886 genes found at Rice DB. The GO approach revealed similar regulation of several families of stress-responsive genes in RGA1 mutant. The Genevestigator analysis of the stress-responsive subset of the RGA1-regulated genes from STIFDB revealed cold and drought-responsive clusters. Meta data analysis at Rice DB revealed large stress-response categories such as cold (878 up/810 down), drought (882 up/837 down), heat (913 up/777 down), and salt stress (889 up/841 down). One thousand four hundred ninety-eight of them are common to all the four abiotic stresses, followed by fewer genes common to smaller groups of stresses. The RGA1 regulated genes that uniquely respond to individual stresses include 111 in heat stress, eight each in cold only and drought only stresses, and two genes in salt stress only. The common DEGs (1498) belong to pathways such as the synthesis of polyamine, glycine-betaine, proline, and trehalose. Some of the common DEGs belong to abiotic stress signaling pathways such as calcium-dependent pathway, ABA independent and dependent pathway, and MAP kinase pathway in the RGA1 mutant. Gene ontology of the common stress responsive DEGs revealed 62 unique molecular functions such as transporters, enzyme regulators, transferases, hydrolases, carbon and protein metabolism, binding to nucleotides, carbohydrates, receptors and lipids, morphogenesis, flower development, and cell homeostasis. We also mined 63 miRNAs that bind to the stress responsive transcripts identified in this study, indicating their post-transcriptional regulation. Overall, these results indicate the potentially extensive role of RGA1 in the regulation of multiple abiotic stresses in rice for further validation. PMID- 26858736 TI - Class-Specific Evolution and Transcriptional Differentiation of 14-3-3 Family Members in Mesohexaploid Brassica rapa. AB - 14-3-3s are highly conserved, multigene family proteins that have been implicated in modulating various biological processes. The presence of inherent polyploidy and genome complexity has limited the identification and characterization of 14-3 3 proteins from globally important Brassica crops. Through data mining of Brassica rapa, the model Brassica genome, we identified 21 members encoding 14-3 3 proteins namely, BraA.GRF14.a to BraA.GRF14.u. Phylogenetic analysis indicated that B. rapa contains both epsilon (epsilon) and non-epsilon 14-3-3 isoforms, having distinct intron-exon structural organization patterns. The non-epsilon isoforms showed lower divergence rate (Ks < 0.45) compared to epsilon protein isoforms (Ks > 0.48), suggesting class-specific divergence pattern. Synteny analysis revealed that mesohexaploid B. rapa genome has retained 1-5 orthologs of each Arabidopsis 14-3-3 gene, interspersed across its three fragmented sub genomes. qRT-PCR analysis showed that 14 of the 21 BraA.GRF14 were expressed, wherein a higher abundance of non-epsilon transcripts was observed compared to the epsilon genes, indicating class-specific transcriptional bias. The BraA.GRF14 genes showed distinct expression pattern during plant developmental stages and in response to abiotic stress, phytohormone treatments, and nutrient deprivation conditions. Together, the distinct expression pattern and differential regulation of BraA.GRF14 genes indicated the occurrence of functional divergence of B. rapa 14-3-3 proteins during plant development and stress responses. PMID- 26858737 TI - Genome-Wide Identification of QTL for Seed Yield and Yield-Related Traits and Construction of a High-Density Consensus Map for QTL Comparison in Brassica napus. AB - Seed yield (SY) is the most important trait in rapeseed, is determined by multiple seed yield-related traits (SYRTs) and is also easily subject to environmental influence. Many quantitative trait loci (QTLs) for SY and SYRTs have been reported in Brassica napus; however, no studies have focused on seven agronomic traits simultaneously affecting SY. Genome-wide QTL analysis for SY and seven SYRTs in eight environments was conducted in a doubled haploid population containing 348 lines. Totally, 18 and 208 QTLs for SY and SYRTs were observed, respectively, and then these QTLs were integrated into 144 consensus QTLs using a meta-analysis. Three major QTLs for SY were observed, including cqSY-C6-2 and cqSY-C6-3 that were expressed stably in winter cultivation area for 3 years and cqSY-A2-2 only expressed in spring rapeseed area. Trait-by-trait meta-analysis revealed that the 144 consensus QTLs were integrated into 72 pleiotropic unique QTLs. Among them, all the unique QTLs affected SY, except for uq.A6-1, including uq.A2-3, uq.C1-2, uq.C1-3, uq.C6-1, uq.C6-5, and uq.C6-6 could also affect more than two SYRTs. According to the constructed high-density consensus map and QTL comparison from literatures, 36 QTLs from five populations were co-localized with QTLs identified in this study. In addition, 13 orthologous genes were observed, including five each gene for SY and thousand seed weight, and one gene each for biomass yield, branch height, and plant height. The genomic information of these QTLs will be valuable in hybrid cultivar breeding and in analyzing QTL expression in different environments. PMID- 26858738 TI - Transient Glyco-Engineering to Produce Recombinant IgA1 with Defined N- and O Glycans in Plants. AB - The production of therapeutic antibodies to combat pathogens and treat diseases, such as cancer is of great interest for the biotechnology industry. The recent development of plant-based expression systems has demonstrated that plants are well-suited for the production of recombinant monoclonal antibodies with defined glycosylation. Compared to immunoglobulin G (IgG), less effort has been undertaken to express immunoglobulin A (IgA), which is the most prevalent antibody class at mucosal sites and a promising candidate for novel recombinant biopharmaceuticals with enhanced anti-tumor activity. Here, we transiently expressed recombinant human IgA1 against the VP8* rotavirus antigen in glyco engineered DeltaXT/FT Nicotiana benthamiana plants. Mass spectrometric analysis of IgA1 glycopeptides revealed the presence of complex biantennary N-glycans with terminal N-acetylglucosamine present on the N-glycosylation site of the CH2 domain in the IgA1 alpha chain. Analysis of the peptide carrying nine potential O glycosylation sites in the IgA1 alpha chain hinge region showed the presence of plant-specific modifications including hydroxyproline formation and the attachment of pentoses. By co-expression of enzymes required for initiation and elongation of human O-glycosylation it was possible to generate disialylated mucin-type core 1 O-glycans on plant-produced IgA1. Our data demonstrate that DeltaXT/FT N. benthamiana plants can be engineered toward the production of recombinant IgA1 with defined human-type N- and O-linked glycans. PMID- 26858739 TI - Biofuel Potential of Plants Transformed Genetically with NAC Family Genes. AB - NAC genes contribute to enhance survivability of plants under conditions of environmental stress and in secondary growth of the plants, thereby building biomass. Thus, genetic transformation of plants using NAC genes provides a possibility to tailor biofuel plants. Over-expression studies have indicated that NAC family genes can provide tolerance to various biotic and abiotic stresses, either by physiological or biochemical changes at the cellular level, or by affecting visible morphological and anatomical changes, for example, by development of lateral roots in a number of plants. Over-expression of these genes also work as triggers for development of secondary cell walls. In our laboratory, we have observed a NAC gene from Lepidium latifolium contributing to both enhanced biomass as well as cold stress tolerance of model plants tobacco. Thus, we have reviewed all the developments of genetic engineering using NAC genes which could enhance the traits required for biofuel plants, either by enhancing the stress tolerance or by enhancing the biomass of the plants. PMID- 26858740 TI - Burkholderia phytofirmans Inoculation-Induced Changes on the Shoot Cell Anatomy and Iron Accumulation Reveal Novel Components of Arabidopsis-Endophyte Interaction that Can Benefit Downstream Biomass Deconstruction. AB - It is known that plant growth promoting bacteria (PGPB) elicit positive effects on plant growth and biomass yield. However, the actual mechanism behind the plant PGPB interaction is poorly understood, and the literature is scarce regarding the thermochemical pretreatability and enzymatic degradability of biomass derived from PGPB-inoculated plants. Most recent transcriptional analyses of PGPB strain Burkholderia phytofirmans PsJN inoculating potato in literature and Arabidopsis in our present study have revealed the expression of genes for ferritin and the biosynthesis and transport of siderophores (i.e., the molecules with high affinity for iron), respectively. The expression of such genes in the shoots of PsJN-inoculated plants prompted us to propose that PsJN-inoculation can improve the host plant's iron uptake and accumulation, which facilitates the downstream plant biomass pretreatment and conversion to simple sugars. In this study, we employed B. phytofirmans PsJN to inoculate the Arabidopsis thaliana plants, and conducted the first investigation for its effects on the biomass yield, the anatomical organization of stems, the iron accumulation, and the pretreatment and enzymatic hydrolysis of harvested biomass. The results showed that the strain PsJN stimulated plant growth in the earlier period of plant development and enlarged the cell size of stem piths, and it also indeed enhanced the essential metals uptake and accumulation in host plants. Moreover, we found that the PsJN inoculated plant biomass released more glucose and xylose after hot water pretreatment and subsequent co-saccharification, which provided a novel insight into development of lignocellulosic biofuels from renewable biomass resources. PMID- 26858741 TI - Enhancing Heat Tolerance of the Little Dogwood Cornus canadensis L. f. with Introduction of a Superoxide Reductase Gene from the Hyperthermophilic Archaeon Pyrococcus furiosus. AB - Production of reactive oxygen species (ROS) can be accelerated under various biotic and abiotic stresses causing lipid peroxidation, protein degradation, enzyme inactivation, and DNA damage. Superoxide reductase (SOR) is a novel antioxidant enzyme from Pyrococcus furiosus and is employed by this anaerobic hyperthermophilic archaeon for efficient detoxification of ROS. In this study, SOR was introduced into a flowering plant Cornus canadensis to enhance its heat tolerance and reduce heat induced damage. A fusion construct of the SOR gene and Green Fluorescent Protein gene (GFP) was introduced into C. canadensis using Agrobacterium-mediated transformation. Heat tolerance of the GFP-SOR expressing transgenic plants was investigated by observing morphological symptoms of heat injury and by examining changes in photosynthesis, malondialdehyde (MDA), and proline levels in the plants. Our results indicate that the expression of the P. furiosus SOR gene in the transgenic plants alleviated lipid peroxidation of cell membranes and photoinhibition of PS II, and decreased the accumulation of proline at 40 degrees C. After a series of exposures to increasing temperatures, the SOR transgenic plants remained healthy and green whereas most of the non-transgenic plants dried up and were unable to recover. While it had previously been reported that expression of SOR in Arabidopsis enhanced heat tolerance, this is the first report of the successful demonstration of improved heat tolerance in a non-model plant resulting from the introduction of P. furiosus SOR. The study demonstrates the potential of SOR for crop improvement and that inherent limitations of plant heat tolerance can be ameliorated with P. furiosus SOR. PMID- 26858742 TI - Molecular Evolution and Functional Diversification of Replication Protein A1 in Plants. AB - Replication protein A (RPA) is a heterotrimeric, single-stranded DNA binding complex required for eukaryotic DNA replication, repair, and recombination. RPA is composed of three subunits, RPA1, RPA2, and RPA3. In contrast to single RPA subunit genes generally found in animals and yeast, plants encode multiple paralogs of RPA subunits, suggesting subfunctionalization. Genetic analysis demonstrates that five Arabidopsis thaliana RPA1 paralogs (RPA1A to RPA1E) have unique and overlapping functions in DNA replication, repair, and meiosis. We hypothesize here that RPA1 subfunctionalities will be reflected in major structural and sequence differences among the paralogs. To address this, we analyzed amino acid and nucleotide sequences of RPA1 paralogs from 25 complete genomes representing a wide spectrum of plants and unicellular green algae. We find here that the plant RPA1 gene family is divided into three general groups termed RPA1A, RPA1B, and RPA1C, which likely arose from two progenitor groups in unicellular green algae. In the family Brassicaceae the RPA1B and RPA1C groups have further expanded to include two unique sub-functional paralogs RPA1D and RPA1E, respectively. In addition, RPA1 groups have unique domains, motifs, cis elements, gene expression profiles, and pattern of conservation that are consistent with proposed functions in monocot and dicot species, including a novel C-terminal zinc-finger domain found only in plant RPA1C-like sequences. These results allow for improved prediction of RPA1 subunit functions in newly sequenced plant genomes, and potentially provide a unique molecular tool to improve classification of Brassicaceae species. PMID- 26858744 TI - Corrigendum: Salicylic acid modulates levels of phosphoinositide dependent phospholipase C substrates and products to remodel the Arabidopsis suspension cell transcriptome. AB - [This corrects the article on p. 608 in vol. 5, PMID: 25426125.]. PMID- 26858743 TI - Comprehensive Comparative Genomic and Transcriptomic Analyses of the Legume Genes Controlling the Nodulation Process. AB - Nitrogen is one of the most essential plant nutrients and one of the major factors limiting crop productivity. Having the goal to perform a more sustainable agriculture, there is a need to maximize biological nitrogen fixation, a feature of legumes. To enhance our understanding of the molecular mechanisms controlling the interaction between legumes and rhizobia, the symbiotic partner fixing and assimilating the atmospheric nitrogen for the plant, researchers took advantage of genetic and genomic resources developed across different legume models (e.g., Medicago truncatula, Lotus japonicus, Glycine max, and Phaseolus vulgaris) to identify key regulatory protein coding genes of the nodulation process. In this study, we are presenting the results of a comprehensive comparative genomic analysis to highlight orthologous and paralogous relationships between the legume genes controlling nodulation. Mining large transcriptomic datasets, we also identified several orthologous and paralogous genes characterized by the induction of their expression during nodulation across legume plant species. This comprehensive study prompts new insights into the evolution of the nodulation process in legume plant and will benefit the scientific community interested in the transfer of functional genomic information between species. PMID- 26858745 TI - A Quantitative Assessment of Factors Affecting the Technological Development and Adoption of Companion Diagnostics. AB - Rapid innovation in (epi)genetics and biomarker sciences is driving a new drug development and product development pathway, with the personalized medicine era dominated by biologic therapeutics and companion diagnostics. Companion diagnostics (CDx) are tests and assays that detect biomarkers and specific mutations to elucidate disease pathways, stratify patient populations, and target drug therapies. CDx can substantially influence the development and regulatory approval for certain high-risk biologics. However, despite the increasingly important role of companion diagnostics in the realization of personalized medicine, in the USA, there are only 23 Food and Drug Administration (FDA) approved companion diagnostics on the market for 11 unique indications. Personalized medicines have great potential, yet their use is currently constrained. A major factor for this may lie in the increased complexity of the companion diagnostic and corresponding therapeutic development and adoption pathways. Understanding the market dynamics of companion diagnostic/therapeutic (CDx/Rx) pairs is important to further development and adoption of personalized medicine. Therefore, data collected on a variety of factors may highlight incentives or disincentives driving the development of companion diagnostics. Statistical analysis for 36 hypotheses resulted in two significant relationships and 34 non-significant relationships. The sensitivity of the companion diagnostic was the only factor that significantly correlated with the price of the companion diagnostic. This result indicates that while there is regulatory pressure for the diagnostic and pharmaceutical industry to collaborate and co-develop companion diagnostics for the approval of personalized therapeutics, there seems to be a lack of parallel economic collaboration to incentivize development of companion diagnostics. PMID- 26858747 TI - Particle Swarm Optimization with Double Learning Patterns. AB - Particle Swarm Optimization (PSO) is an effective tool in solving optimization problems. However, PSO usually suffers from the premature convergence due to the quick losing of the swarm diversity. In this paper, we first analyze the motion behavior of the swarm based on the probability characteristic of learning parameters. Then a PSO with double learning patterns (PSO-DLP) is developed, which employs the master swarm and the slave swarm with different learning patterns to achieve a trade-off between the convergence speed and the swarm diversity. The particles in the master swarm and the slave swarm are encouraged to explore search for keeping the swarm diversity and to learn from the global best particle for refining a promising solution, respectively. When the evolutionary states of two swarms interact, an interaction mechanism is enabled. This mechanism can help the slave swarm in jumping out of the local optima and improve the convergence precision of the master swarm. The proposed PSO-DLP is evaluated on 20 benchmark functions, including rotated multimodal and complex shifted problems. The simulation results and statistical analysis show that PSO DLP obtains a promising performance and outperforms eight PSO variants. PMID- 26858746 TI - Stress-Induced Accumulation of DcAOX1 and DcAOX2a Transcripts Coincides with Critical Time Point for Structural Biomass Prediction in Carrot Primary Cultures (Daucus carota L.). AB - Stress-adaptive cell plasticity in target tissues and cells for plant biomass growth is important for yield stability. In vitro systems with reproducible cell plasticity can help to identify relevant metabolic and molecular events during early cell reprogramming. In carrot, regulation of the central root meristem is a critical target for yield-determining secondary growth. Calorespirometry, a tool previously identified as promising for predictive growth phenotyping has been applied to measure the respiration rate in carrot meristem. In a carrot primary culture system (PCS), this tool allowed identifying an early peak related with structural biomass formation during lag phase of growth, around the 4th day of culture. In the present study, we report a dynamic and correlated expression of carrot AOX genes (DcAOX1 and DcAOX2a) during PCS lag phase and during exponential growth. Both genes showed an increase in transcript levels until 36 h after explant inoculation, and a subsequent down-regulation, before the initiation of exponential growth. In PCS growing at two different temperatures (21 degrees C and 28 degrees C), DcAOX1 was also found to be more expressed in the highest temperature. DcAOX genes' were further explored in a plant pot experiment in response to chilling, which confirmed the early AOX transcript increase prior to the induction of a specific anti-freezing gene. Our findings point to DcAOX1 and DcAOX2a as being reasonable candidates for functional marker development related to early cell reprogramming. While the genomic sequence of DcAOX2a was previously described, we characterize here the complete genomic sequence of DcAOX1. PMID- 26858748 TI - Usefulness of Acoustic Monitoring of Respiratory Rate in Patients Undergoing Endoscopic Submucosal Dissection. AB - Aim. The study assessed the usefulness of a recently developed method for respiratory rate (RR) monitoring in patients undergoing endoscopic submucosal dissection (ESD) under deep sedation. Methods. Study subjects comprised 182 consecutive patients with esophageal cancer or gastric cancer undergoing ESD. The usefulness of acoustic RR monitoring was assessed by retrospectively reviewing the patients' records for age, gender, height, weight, past history, serum creatinine, RR before ESD, and total dose of sedative. Results. Respiratory suppression was present in 37.9% of (69/182) patients. Continuous monitoring of RR led to detection of respiratory suppression in all these patients. RR alone was decreased in 24 patients, whereas both RR and blood oxygen saturation were decreased in 45 patients. Univariate analysis showed female gender, height, weight, and RR before treatment to be significantly associated with respiratory suppression. Multivariate analysis showed RR before treatment to be the only significant independent predictor [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.73-0.95, and P = 0.006] of respiratory suppression. Conclusion. In this study, the difference in RR before treatment between patients with and without respiratory suppression was subtle. Therefore, we suggest that acoustic RR monitoring should be considered in patients undergoing ESD under sedation to prevent serious respiratory complications. PMID- 26858749 TI - Preoperative Nutritional Therapy Reduces the Risk of Anastomotic Leakage in Patients with Crohn's Disease Requiring Resections. AB - Background. The rate of anastomotic leakage is high in surgeries for Crohn's disease, and therefore a temporary diverting stoma is often needed. We conducted this study to investigate whether preoperative nutritional therapy could reduce the risk of anastomotic leakage while decreasing the frequency of temporary stoma formation. Methods. This was a retrospective study. Patients requiring bowel resections due to Crohn's disease were reviewed. The rate of anastomotic leakage and temporary diverting stoma was compared between patients who received preoperative nutritional therapy and those on a normal diet before surgery. Possible predictive factors for anastomotic leakage were also analyzed. Results. One hundred and fourteen patients undergoing 123 surgeries were included. Patients in nutritional therapy (NT) group had a significantly lower level of C reactive protein on the day before surgery. Patients in NT group suffered less anastomotic leakage (2.3% versus 17.9%, P = 0.023) and less temporary diverting stoma (22.8% versus 40.9%, P = 0.036). Serum albumin of the day before surgery <=35 g/L and preoperative nutritional therapy were identified as factors which independently affected the rate of anastomotic leakage. Conclusion. Preoperative nutritional therapy reduced the risk of anastomotic leakage and the frequency of temporary diverting stoma formation in patients with Crohn's disease requiring resections. PMID- 26858750 TI - Efficacy of 7-Day and 14-Day Triple Therapy Regimens for the Eradication of Helicobacter pylori: A Comparative Study in a Cohort of Romanian Patients. AB - Objective. This study compared the eradication rates of of Helicobacter pylori (HP) infection by a 7-day and 14-day anti-HP regimen. Materials and Methods. An open, randomized, prospective study was performed to evaluate the response to anti-HP treatment in adult HP-positive patients following a 7-day course (Regimen A) of a proton pump inhibitor in association with clarithromycin and amoxicillin compared to a 14-day course (Regimen B). Gastric biopsies were performed at baseline and two months after anti-HP treatment. Results. Seventy-eight patients aged 18-64 years (28 males, 50 females) diagnosed with HP infection were included. Fifty-two (66.7%) patients received Regimen B and 26 (33.3%) Regimen A. The overall eradication rate was 70.5%. Better treatment response (p < 0.01) was seen in Regimen B (44/52, 84.2% versus 11/26, 42.3%). Significant improvement in histological features was seen in regimen B. There has been significant overall reduction in endoscopic aspects of gastric and duodenal lesions in both regimens. Younger patients <=35 years had a better response to Regimen B. Better treatment response was seen in women, urban residents, and those with tertiary level of education in both groups. Conclusion. 14-day anti-HP regimen offered a significant better overall eradication of HP in study population. PMID- 26858751 TI - Surrounding Gastric Mucosa Findings Facilitate Diagnosis of Gastric Neoplasm as Gastric Adenoma or Early Gastric Cancer. AB - Background and Aim. It is difficult to master the skill of discriminating gastric adenoma from early gastric cancer by conventional endoscopy or magnifying endoscopy combined with narrow-band imaging, because the colors and morphologies of these neoplasms are occasionally similar. We focused on the surrounding gastric mucosa findings in order to determine how to discriminate between early gastric cancer and gastric adenoma by analyzing the characteristics of the gastric background mucosa. Methods. We retrospectively examined 146 patients who underwent endoscopic submucosal dissection for gastric neoplasm between October 2009 and January 2015. The boundary of atrophic gastritis was classified endoscopically according to the Kimura-Takemoto classification system. Of 146 lesions, 63 early gastric cancers and 21 gastric adenomas were ultimately evaluated and assessed. Results. Almost all gastric adenomas were accompanied by open-type gastritis, whereas 47 and 16 early gastric cancers were accompanied by open-type and closed-type gastritis, respectively (p = 0.037). Conclusions. The evaluation of the boundary of atrophic gastritis associated with gastric neoplasms appears to be useful for discrimination between early gastric cancer and gastric adenoma. When gastric neoplasm is present in the context of surrounding localized gastric atrophy, gastric cancer is probable but not certain. PMID- 26858752 TI - Characteristics of Pediatric Crohn's Disease in Saudi Children: A Multicenter National Study. AB - Background and Aims. Crohn's disease (CD) is an evolving disease in KSA. Little is known about its characteristics in the Saudi population. The aims of this study were to describe the characteristics of Saudi children with CD and to determine whether the characteristics of CD in KSA are different from those seen in Western countries. Methods. In this study, children younger than eighteen years of age diagnosed with CD between January 2003 and December 2012 were included. Results. Of 330 patients identified, 186 (56.4%) were males. The median age at diagnosis was 15.8 years. A positive family history for IBD in first degree relatives occurred in 13.6% of patients. The most common symptoms were abdominal pain (84.2%), weight loss (75.2%), and diarrhea (71.8%). The main disease location was ileocolonic (42.1%) and the main disease behavior was nonstricturing and nonpenetrating (63.6%). Perianal involvement was seen in 60 (18.2%) patients. Laboratory findings revealed anemia in 57.9% of patients, low albumin in 34.5%, and high CRP in 39.4%. Conclusions. Saudi children with CD have lower frequency of first-degree relatives with IBD, lower prevalence of early onset disease, longer diagnostic delay, higher prevalence of growth failure, and greater frequency of stricturing and penetrating disease behavior compared to Western patients. PMID- 26858753 TI - Complimentary Imaging Modalities for Investigating Obscure Gastrointestinal Bleeding: Capsule Endoscopy, Double-Balloon Enteroscopy, and Computed Tomographic Enterography. AB - Objectives. The complimentary value of computed tomographic enterography (CTE) and double-balloon enteroscopy (DBE) combined with capsule endoscopy (CE) was evaluated in the diagnosis of obscure gastrointestinal bleeding (OGIB). Methods. Patients who received CE examinations at Ruijin Hospital between July 2007 and July 2014 with the indication of OGIB were identified, and those who also underwent DBE and/or CTE were included. Their clinical information was retrieved, and results from each test were compared with findings from the other two examinations. Results. The overall diagnostic yield of CE was comparable with DBE (73.9% versus 60.9%) but was significantly higher than the yield of CTE (87% versus 25%, p < 0.001). The diagnostic yield of angiodysplasia at CE was significantly higher than CTE (73% versus 8%, p < 0.001) and DBE (39.1% versus 17.4%, p = 0.013), while no significant difference was found between the three approaches for small bowel tumors. DBE and CTE identified small bowel diseases undetected or undetermined by CE. Conversely, CE improved diagnosis in the cases with negative CTE and DBE, and findings at initial CE directed further diagnosis made by DBE. Conclusions. Combination of the three diagnostic platforms provides complementary value in the diagnosis of OGIB. PMID- 26858754 TI - Rectal Tumour Staging with Endorectal Ultrasound: Is There Any Difference between Western and Eastern European Countries? AB - Background. Rectal tumour management depends highly on locoregional extension. Rectal endoscopic ultrasound (ERUS) is a good alternative to computed tomography and magnetic resonance imaging. However, in Hungary only a small amount of rectal tumours is examined with ERUS. Methods. Our retrospective study (2006-2012) evaluates the diagnostic accuracy of ERUS and compares the results, the first data from Central Europe, with those from Western Europe. The effect of neoadjuvant therapy, rectal probe type, and investigator's experience were also assessed. Results. 311 of the 647 ERUS assessed locoregional extension. Histological comparison was available in 177 cases: 67 patients underwent surgery alone; 110 received neoadjuvant chemoradiotherapy (CRT); ERUS preceded CRT in 77 and followed it in 33 patients. T-staging was accurate in 72% of primarily operated patients. N-staging was less accurate (62%). CRT impaired staging accuracy (64% and 59% for T- and N-staging). Rigid probes were more accurate (79%). At least 30 examinations are needed to master the technique. Conclusions. The sensitivity of ERUS complies with the literature. ERUS is easy to learn and more accurate in early stages but unnecessary for restaging after CRT. Staging accuracy is similar in Western and Central Europe, although the number of examinations should be increased. PMID- 26858755 TI - Lower Viral Response to Pegylated Interferon Alpha 2a Treatment of Chronic Hepatitis B in Roma People in Eastern Slovakia. AB - Aim. To evaluate the compliance and virological response to pegylated interferon alpha 2a treatment of chronic hepatitis B in Roma population compared to majority Caucasian population in Slovakia. Methods. Retrospective evaluation of a cohort of all Roma patients treated with pegylated interferon alpha 2a from 2007 to 2013 in 3 centers for treatment of chronic viral hepatitis B. The Study included 43 Roma patients with chronic viral hepatitis B and randomly selected control group. Treatment duration was 48 weeks. Viral response was evaluated after 24 weeks, at the end of treatment, and 24 weeks after the end of treatment. Results. Complete treatment course was finished by 79.1% of Roma patients compared to all patients from the control group (p = 0.0009). There was a tendency toward lower viral response rate in Roma at all time points; however significant difference was only at end of treatment viral response (51.2% Roma versus 81.4% majority, p = 0.003). We also did not find significant difference at the rate of HBsAg loss. Conclusion. Roma patients with chronic hepatitis B have significantly worse compliance to treatment with pegylated interferon and they have significantly lower rate of end of treatment viral response. PMID- 26858756 TI - Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients. AB - Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6) in colorectal cancer (CRC). Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS) and disease-free survival (DFS) rates according to IL-6 status were calculated for all patients and according to disease stage. Results. The mean IL 6 level was 6.6 pg/mL in CRC patients and 2.6 pg/mL in healthy controls. Using a cutoff of 6.3 pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP) and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients. Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence. PMID- 26858757 TI - Protocol for Bone Augmentation with Simultaneous Early Implant Placement: A Retrospective Multicenter Clinical Study. AB - Purpose. To present a novel protocol for alveolar bone regeneration in parallel to early implant placement. Methods. 497 patients in need of extraction and early implant placement with simultaneous bone augmentation were treated in a period of 10 years. In all patients the same specific method was followed and grafting was performed utilizing in situ hardening fully resorbable alloplastic grafting materials consisting of beta-tricalcium phosphate and calcium sulfate. The protocol involved atraumatic extraction, implant placement after 4 weeks with simultaneous bone augmentation, and loading of the implant 12 weeks after placement and grafting. Follow-up periods ranged from 6 months to 10 years (mean of 4 years). Results. A total of 601 postextraction sites were rehabilitated in 497 patients utilizing the novel protocol. Three implants failed before loading and three implants failed one year after loading, leaving an overall survival rate of 99.0%. Conclusions. This standardized protocol allows successful long term functional results regarding alveolar bone regeneration and implant rehabilitation. The concept of placing the implant 4 weeks after extraction, augmenting the bone around the implant utilizing fully resorbable, biomechanically stable, alloplastic materials, and loading the implant at 12 weeks seems to offer advantages when compared with traditional treatment modalities. PMID- 26858758 TI - Autologous Fat Grafting Reduces Pain in Irradiated Breast: A Review of Our Experience. AB - Introduction. Pain syndromes affect women after conservative and radical breast oncological procedures. Radiation therapy influences their development. We report autologous fat grafting therapeutical role in treating chronic pain in irradiated patients. Materials and Methods. From February 2006 to November 2014, we collect a total of 209 patients who meet the definition of "Postmastectomy Pain Syndrome" (PMPS) and had undergone mastectomy with axillary dissection (113 patients) or quadrantectomy (96 patients). Both procedures were followed by radiotherapy. We performed fat grafting following Coleman's procedure. Mean amount of adipose tissue injected was 52 cc (+/-8.9 cc) per breast. Seventy-eight in 209 patients were not treated surgically and were considered as control group. Data were gathered through preoperative and postoperative VAS questionnaires; analgesic drug intake was recorded. Results. The follow-up was at 12 months (range 11.7 13.5 months). In 120 treated patients we detected pain decrease (mean +/- SD point reduction, 3.19 +/- 2.86). Forty-eight in 59 patients stopped their analgesic drug therapy. Controls reported a mean +/- SD decrease of pain of 1.14 +/- 2.72. Results showed that pain decreased significantly in patients treated (p < 0.005, Wilcoxon rank-sum test). Conclusion. Our 8-year experience confirms fat grafting effectiveness in decreasing neuropathic pain. PMID- 26858760 TI - Current Recommendations for Pneumococcal Vaccination of Children and Adults. PMID- 26858759 TI - Cancer Stem Cell Plasticity as Tumor Growth Promoter and Catalyst of Population Collapse. AB - It is increasingly argued that cancer stem cells are not a cellular phenotype but rather a transient state that cells can acquire, either through intrinsic signaling cascades or in response to environmental cues. While cancer stem cell plasticity is generally associated with increased aggressiveness and treatment resistance, we set out to thoroughly investigate the impact of different rates of plasticity on early and late tumor growth dynamics and the response to therapy. We develop an agent-based model of cancer stem cell driven tumor growth, in which plasticity is defined as a spontaneous transition between stem and nonstem cancer cell states. Simulations of the model show that plasticity can substantially increase tumor growth rate and invasion. At high rates of plasticity, however, the cells get exhausted and the tumor will undergo spontaneous remission in the long term. In a series of in silico trials, we show that such remission can be facilitated through radiotherapy. The presented study suggests that stem cell plasticity has rather complex, nonintuitive implications on tumor growth and treatment response. Further theoretical, experimental, and integrated studies are needed to fully decipher cancer stem cell plasticity and how it can be harnessed for novel therapeutic approaches. PMID- 26858761 TI - Impact of Comorbid Ischemic Heart Disease on Short-Term Outcomes of Patients Hospitalized for Acute Exacerbations of COPD. AB - BACKGROUND: Ischemic heart disease (IHD) is a leading cause of mortality and morbidity in patients with COPD. The contribution of IHD to acute outcomes in patients with acute exacerbation of COPD (AECOPD) is not known in detail. The present study assessed the effect of comorbid IHD on length of stay (LOS), risk of intensive care unit (ICU) admission and death as indicators of the short-term outcomes for patients hospitalized for AECOPD. MATERIALS AND METHODS: Medical records of patients hospitalized for AECOPD from September 2008 to March 2014 were reviewed. Data extracted from patient records regarding the presence of comorbidities and the markers of disease severity were analyzed using logistic regression for ICU admission and mortality, the Kaplan-Meier method, log rank test and Cox regression for LOS. RESULTS: Of 507 separate admissions, 146 episodes (28.8%) occurred in patients with IHD. The median LOS was 7 days [interquartile range (IQR) 6, 11] in patients with IHD versus 6 days (IQR 5, 8) for patients without IHD. After adjustment for confounders, LOS was found to be 26% longer (p=0.033) for patients with IHD. The adjusted odds ratio for the risk of ICU admission and death in patients with IHD was 2.97 and 3.86, respectively. CONCLUSION: Patients hospitalized for AECOPD with comorbid IHD had longer LOS, greater risk for ICU admission and death. It seems that this group is a particular COPD subtype with a more severe degree of COPD and poorer acute outcomes that may influence optimal management. PMID- 26858762 TI - High Seroprevalence of Bordetella pertussis in Patients with Chronic Obstructive Pulmonary Disease: A Case-Control Study. AB - BACKGROUND: Bordetella pertussis has been suggested to take part in the acute exacerbation of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the association between B. pertussis and COPD. MATERIALS AND METHODS: In this case-control study, 90 patients with COPD and 90 age- and sex- matched control subjects were included. Serum samples were tested for anti B. pertussis IgG and IgA by ELISA. A physician completed a questionnaire including demographic characteristics, habitual history and spirometric findings for each patient. RESULTS: Of 90 patients with chronic obstructive pulmonary disease, 66 (51%) had mild, 31 (34.4%) had moderate, and 13 (14.4%) had severe disease. There was no significant association between B. pertussis IgA seropositivity and COPD. Serum levels of anti- B. pertussis IgG were significantly higher in patients with COPD than in the control subjects (P < 0.001). No association was observed between B. pertussis infection and severity of COPD. CONCLUSION: The results suggest that there is an association between B. pertussis infection and COPD. Further studies should be planned to investigate the potential pathogenic mechanisms underlying these associations. PMID- 26858763 TI - An Innovative Method to Enhance the Modified DOTS for TB Patients. AB - BACKGROUND: Nowadays establishing communication and educating patients to enhance their knowledge regarding disease and treatment process at home is one of the most important principles in providing patient care. MATERIALS AND METHODS: A semi-experimental study was done on 57 patients with active pulmonary tuberculosis in two care groups namely professional - family mix directly observed treatment short- course (PFM-DOTS) and family based-DOTS (FB-DOTS). The patients were referred to the tuberculosis and lung diseases research center for diagnosis and treatment of pulmonary tuberculosis. Both the patient and a family supervisor were evaluated regarding their level of knowledge of the disease and the treatment regimen. RESULTS: A significant difference between the degree of knowledge of groups of patients and the groups of family relatives before and after the intervention was indicated, with a higher increase in PFM-DOTS group than in F-B-DOTS group (P< 0.001). In PFM- DOTS group 100% of the patients, and in the FB-DOTS group 86.8% of the patients followed the recommended drug regimen (P<0.001). CONCLUSION: According to the treatment recommendations by the World Health Organization (WHO) for appropriate implementation of DOTS project combating TB, it seems the PFM-DOTS implementation is a more suitable method with greater effects on correct care and treatment of tuberculosis patients. PMID- 26858764 TI - Psychological Symptoms Before and After a 14-Day Initial Inpatient Treatment in Tuberculosis Patients Compared with Their Primary Caregivers and Healthy Controls. AB - BACKGROUND: Tuberculosis (TB) is one of the most challenging public health burdens in the world. Recent research demonstrated high prevalence of mental disorders in TB patients and their caregivers. The purpose of this study was to assess mental health of TB patients and their caregivers in Iran before and after a two-week inpatient treatment and to determine the prevalence of psychological problems in these groups. MATERIALS AND METHODS: A standardized questionnaire (SCL-90) was used to assess psychological symptoms in 146 hospitalized TB patients and their caregivers (n=89). Furthermore, the scores of both target groups were compared with those of a group of healthy individuals (n=85). RESULTS: The mean scores before the start of the initial treatment of the patients were significantly lower for paranoid ideation (P=0.038) and hostility (P= 0.046), and the scores of depression (P=0.046) and somatization (P=0.001) were significantly higher than those of the healthy individuals. The patients scored significantly higher than the caregivers on depression (0.047) and somatization (P< 0.001), whereas the caregivers scored higher than the healthy individuals on paranoid ideation (P= 0.044) and hostility (P= 0.034). Multiple linear regression showed that age, educational level and marital status were factors affecting the mental health of TB patients and their caregivers. The variance in psychological symptoms of the patients was between 10% (paranoid ideation) and 27% (hostility) of the variance in the symptoms of their caregivers. CONCLUSION: Tuberculosis control and treatment programs should not only address issues like continued respiratory symptoms, but should also focus on mental health in TB patients and their caregivers. PMID- 26858765 TI - The Extrapulmonary Manifestations of Systemic Sclerosis on Chest High Resolution Computed Tomography. AB - BACKGROUND: Systemic sclerosis (SS) is a collagen vascular disease of unknown etiology that is characterized by connective tissue abnormalities. This study aimed to evaluate the extra-pulmonary manifestations of SS on chest high resolution computed tomography (HRCT). MATERIALS AND METHODS: The medical records of patients with SS who presented to our hospital in a 10-year period were retrospectively reviewed. Forty patients with SS were included in this study. The extra pulmonary manifestations of SS were evaluated in these patients, including esophageal involvement, pulmonary arterial dilatation, pleural abnormalities, pericardial disease and mediastinal lymph node involvement. RESULTS: The most common extra-pulmonary manifestation was esophageal dilatation, which was detected in 70% of the cases followed by pleural involvement. Pulmonary arterial dilatation was seen in 20%, pleural involvement in 40%, pericardial involvement in 40% and mediastinal lymphadenopathy in 30%. The most common pleural abnormality was diffuse pleural thickening and the most common pericardial abnormality was pericardial effusion. There was an association between the severity of lung fibrosis with the incidence of esophageal dilatation and pulmonary arterial hypertension (PAH) in our series. Patients with SS and interstitial lung disease (ILD) who had PAH, had more severe lung fibrosis than those without PAH. CONCLUSION: Patients with SS may have a variety of extra pulmonary manifestations, which can be detected using HRCT. Our study evidenced that HRCT was useful for detecting extra-pulmonary findings of SS such as esophageal dysmotility and dilatation, enlargement of main pulmonary artery and PAH, pleuropericardial involvement and mediastinal lymphadenopathy. PMID- 26858766 TI - Association between Occupational Accidents and Sleep Apnea in Hospital Staff. AB - BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a common disorder in which instability of the upper airways leads to a reduction or cessation of airflow during sleep. Sleep disorders such as OSAS increase the risk of occupational accidents and impaired work performance. Sleep deprivation during shift increases the risk of occupational accidents among health care employees. The purpose of this study was to determine the association between occupational injuries in hospital staff and the risk of sleep apnea. MATERIALS AND METHODS: This cross sectional study was conducted on hospital staff of Masih Daneshvari Hospital in 2012. In this study, the hospital staff's (715) response to the Berlin questionnaire plus additional information including a history of an occupational accident, night shifts, less than four hours of night sleep, history of smoking, chronic disease and quality of sleep were assessed. Information obtained was analyzed using SPSS 15. RESULTS: In general, 27.6% reported a history of occupational accidents. The incidence of occupational accidents in the high-risk group for sleep apnea was significantly higher than the low-risk group (OR=2.736, CI=1.522-4.917, P=0.001). The results of logistic regression analysis also showed a statistically significant association between occupational accidents and risk of sleep apnea (OR = 2.247, CI = 1.194-4.231, P= 0.012). CONCLUSION: This study showed that the incidence of occupational accidents in the hospital employees is strongly related to the probability of OSA. Therefore, special attention should be directed to respiratory sleep disorders in order to reduce occupational injuries at hospitals. PMID- 26858767 TI - Assessment of Occupational Exposure to Dust and Crystalline Silica in Foundries. AB - BACKGROUND: The term "crystalline silica" refers to crystallized form of SiO2 and quartz, as the most abundant compound on the earth's crust; it is capable of causing silicosis and lung cancer upon inhaling large doses in the course of occupational exposure. The aim of this study was to assess occupational exposure to dust and crystalline silica in foundries in Pakdasht, Iran. MATERIALS AND METHODS: In this study, airborne dust samples were collected on PVC filters (37 mm diameter, 0.8 mm pore size), by using a sampling pump and open face cyclone at a flow rate of 2.2 l/min for a maximum volume of 800 liters. For determining crystalline silica spectrometry was used according to the National Institute of Occupational Safety and Health (NIOSH) method No. 7601 for analysis of samples. RESULTS: Results showed that crystalline silica concentration was higher than NIOSH and the American Conference of Government Industrial Hygienist (ACGIH) allowed extent (0.025 mg/m(3)). Concentration of crystalline silica was 0.02-0.1 mg/m(3). Total dust concentration average was higher than the allowed extent by Permissible Exposure Limit (PEL) of the Occupational Safety and Health Administration (OSHA). CONCLUSION: It is essential to take necessary measures to control crystalline silica dust regarding the fact that 50% of workers are exposed to higher than the allowed extent. PMID- 26858768 TI - Renal Lymphangiectasia: A Curious Cause of Pleural Effusion. AB - Renal lymphangiectasia is a disorder of the lymphatic system of the kidneys, which can be congenital or acquired. Although the exact etiology remains unknown, an obstructive process resulting from several causes, including infection, inflammation or malignant infiltration, has been suggested to be responsible for the acquired form. This disorder may be associated with several pathologies. We report a case of a 24-year-old man with renal lymphangiectasia presenting with polycythemia, ascites and pleural effusion associated with hepatitis C virus (HCV) infection in an intravenous (IV) drug user. Our case is the first in the literature that shows an association between HCV infection and IV drug use. PMID- 26858769 TI - Different and Unpredictable Clinical Outcome of Ruptured Pulmonary Hydatid Cysts. AB - Most authors believe that the best treatment for pulmonary hydatid disease is surgical evacuation. Although albendazole has been used prophylactically before surgery, there are many reports about increased incidence of the rupture of cyst after albendazole therapy, which can cause some complications. In this case report we present a patient with bilateral pulmonary hydatid cyst that was ruptured after using albendazole and different strategies were used for management of each cyst. PMID- 26858770 TI - Germinated Brown Rice Alters Abeta(1-42) Aggregation and Modulates Alzheimer's Disease-Related Genes in Differentiated Human SH-SY5Y Cells. AB - The pathogenesis of Alzheimer's disease involves complex etiological factors, of which the deposition of beta-amyloid (Abeta) protein and oxidative stress have been strongly implicated. We explored the effects of H2O2, which is a precursor for highly reactive hydroxyl radicals, on neurotoxicity and genes related to AD on neuronal cells. Candidate bioactive compounds responsible for the effects were quantified using HPLC-DAD. Additionally, the effects of germinated brown rice (GBR) on the morphology of Abeta(1-42) were assessed by Transmission Electron Microscopy and its regulatory effects on gene expressions were explored. The results showed that GBR extract had several phenolic compounds and gamma-oryzanol and altered the structure of Abeta(1-42) suggesting an antiamyloidogenic effect. GBR was also able to attenuate the oxidative effects of H2O2 as implied by reduced LDH release and intracellular ROS generation. Furthermore, gene expression analyses showed that the neuroprotective effects of GBR were partly mediated through transcriptional regulation of multiple genes including Presenilins, APP, BACE1, BACE2, ADAM10, Neprilysin, and LRP1. Our findings showed that GBR exhibited neuroprotective properties via transcriptional regulation of APP metabolism with potential impact on Abeta aggregation. These findings can have important implications for the management of neurodegenerative diseases like AD and are worth exploring further. PMID- 26858771 TI - The antiviral compound BIT225 inhibits HIV-1 replication in myeloid dendritic cells. AB - BACKGROUND: Previous studies with BIT225 (N-carbamimidoyl-5-(1-methyl-1H-pyrazol 4-yl)-2-naphthamide) have demonstrated a unique antiviral activity that blocks the release of HIV-1 from monocyte-derived macrophages (MDM). Antagonising the ion channel formed by HIV-1 Vpu, BIT225 preferentially targets de novo intracellular virus produced in 'virus-containing compartments' of MDM. In primary infections, dendritic cells (DC) are one of the first cells infected by HIV-1 and can transfer virus to more permissive CD4(+) T cells, making these cells an important target for novel antiviral therapies. To extend previous findings with BIT225, we aimed to further characterise the antiviral activity of BIT225 on HIV-1 replication in monocyte-derived DC (MDDC). RESULTS: The anti-HIV 1 activity of BIT225 was evaluated in vitro within MDDC alone and in co-cultures with activated CD4(+) T cells to examine the effect of the drug on HIV-1 transfer. Antiviral activity was determined by measuring HIV-1 reverse transcriptase activity in the culture supernatant of BIT225 treated and DMSO control cultures. A single dose of BIT225 resulted in a mean (SE) peak inhibition of HIV-1 release from MDDC by 74.5 % (+/-0.6) following 14 days of culture and a 6-fold reduction of HIV-1 transfer to activated uninfected CD4(+) T cells in co culture. CONCLUSIONS: HIV-1 release from MDDC was inhibited by BIT225. This data broadens the drug's antiviral activity profile within cells of the myeloid lineage. These findings suggest a potential role for BIT225 in reducing HIV-1 production and preventing viral dissemination in early and chronic infection and may assist in limiting virus spread with any ongoing viral replication during antiretroviral therapy. PMID- 26858772 TI - A Dual Hesitant Fuzzy Multigranulation Rough Set over Two-Universe Model for Medical Diagnoses. AB - In medical science, disease diagnosis is one of the difficult tasks for medical experts who are confronted with challenges in dealing with a lot of uncertain medical information. And different medical experts might express their own thought about the medical knowledge base which slightly differs from other medical experts. Thus, to solve the problems of uncertain data analysis and group decision making in disease diagnoses, we propose a new rough set model called dual hesitant fuzzy multigranulation rough set over two universes by combining the dual hesitant fuzzy set and multigranulation rough set theories. In the framework of our study, both the definition and some basic properties of the proposed model are presented. Finally, we give a general approach which is applied to a decision making problem in disease diagnoses, and the effectiveness of the approach is demonstrated by a numerical example. PMID- 26858773 TI - Application of Random Forest Survival Models to Increase Generalizability of Decision Trees: A Case Study in Acute Myocardial Infarction. AB - BACKGROUND: Tree models provide easily interpretable prognostic tool, but instable results. Two approaches to enhance the generalizability of the results are pruning and random survival forest (RSF). The aim of this study is to assess the generalizability of saturated tree (ST), pruned tree (PT), and RSF. METHODS: Data of 607 patients was randomly divided into training and test set applying 10 fold cross-validation. Using training sets, all three models were applied. Using Log-Rank test, ST was constructed by searching for optimal cutoffs. PT was selected plotting error rate versus minimum sample size in terminal nodes. In construction of RSF, 1000 bootstrap samples were drawn from the training set. C index and integrated Brier score (IBS) statistic were used to compare models. RESULTS: ST provides the most overoptimized statistics. Mean difference between C index in training and test set was 0.237. Corresponding figure in PT and RSF was 0.054 and 0.007. In terms of IBS, the difference was 0.136 in ST, 0.021 in PT, and 0.0003 in RSF. CONCLUSION: Pruning of tree and assessment of its performance of a test set partially improve the generalizability of decision trees. RSF provides results that are highly generalizable. PMID- 26858774 TI - Short report: self-reported psychopathic traits in Finnish and Dutch samples of non-referred adolescents: exploration of cultural differences. AB - BACKGROUND: Culture-related differences in psychopathic traits have been reported for adults, but for adolescents such knowledge is lacking. The aim of this cross national study was to compare self-reported psychopathic traits between Finnish and Dutch samples of mid-adolescent community youth. METHODS: The Youth Psychopathic traits Inventory (YPI) was filled in by 372 Finnish and 474 Dutch 15 to 16-year-old pupils. As gender-specific differences exist in psychopathic traits, we analyzed the data separately for boys and girls. RESULTS: Dutch boys scored significantly higher than Finnish boys on total and all dimensional scores of the YPI as well as on most sub-dimensional scores. Dutch girls scored significantly higher than Finnish girls on the Affective dimension and on the two corresponding sub-dimensions: remorselessness and callousness. Finnish girls scored significantly higher on grandiosity, which loads to the Interpersonal dimension of the YPI. CONCLUSIONS: Our findings suggest that culture influences the manifestation of psychopathic traits already in adolescence and that this relation is more prominent in boys. PMID- 26858775 TI - The paradox of longer sperm telomeres in older men's testes: a birth-cohort effect caused by transgenerational telomere erosion in the female germline. AB - Longer telomeres in the somatic cells of an individual have been regarded as a marker of youth and biological fitness within a population. Yet, several research groups have reported the surprising findings of longer telomeres in the germ cells of older men, which translated into longer leukocyte telomere length in their offspring. Although all these studies were purely cross-sectional, a longitudinal trend in the aging testes of individual males was taken for granted. Recently, a high-profile study reported a negative birth-cohort effect on leukocyte mean telomere length in human populations, namely the progressive loss of telomeric sequence between healthy human generations. This is what I based my theory of telomere-driven macroevolution on, 12 years ago. On the basis of published data on telomere length inheritance, I identified the source of human intergenerational telomere erosion in the female germline. Accordingly, because of the resulting birth-cohort effect, there is no need for any paradoxical telomere lengthening in older men's gonads to interpret the old-father-long telomered-offspring data. PMID- 26858777 TI - The social benefits of private infectious disease-risk mitigation. AB - Does society benefit from private measures to mitigate infectious disease risks? Since mitigation reduces both peak prevalence and the number of people who fall ill, the answer might appear to be yes. But mitigation also prolongs epidemics and therefore the time susceptible people engage in activities to avoid infection. These avoidance activities come at a cost-in lost production or consumption, for example. Whether private mitigation yields net social benefits depends on the social weight given to the costs of illness and illness avoidance, now and into the future. We show that, for a large class of infectious diseases, private risk mitigation is socially beneficial. However, in cases where society discounts the future at either very low or very high rates relative to private individuals, or where it places a low weight on the private cost of illness, the social cost of illness under proportionate mixing (doing nothing) may be lower than the social cost of illness under preferential mixing (avoiding infectious individuals). That is, under some circumstances, society would prefer shorter, more intense epidemics without avoidance costs over longer, less intense epidemics with avoidance costs. A sobering (although not surprising) implication of this is that poorer societies should be expected to promote less private disease-risk mitigation than richer societies. PMID- 26858776 TI - Recruiting a U.S. national sample of HIV-negative gay and bisexual men to complete at-home self-administered HIV/STI testing and surveys: Challenges and Opportunities. AB - We describe enrollment for the One Thousand Strong panel, present characteristics of the panel relative to other large U.S. national studies of gay and bisexual men (GBM), and examine demographic and behavioral characteristics that were associated with passing enrollment milestones. A U.S. national sample of HIV negative men were enrolled via an established online panel of over 22,000 GBM. Participants (n = 1071) passed three milestones to join our panel. Milestone 1 was screening eligible and providing informed consent. Milestone 2 involved completing an hour-long at-home computer-assisted self-interview (CASI) survey. Milestone 3 involved completing at-home self-administered rapid HIV testing and collecting/returning urine and rectal samples for gonorrhea and chlamydia testing. Compared to those who completed milestones: those not passing milestone 1 were more likely to be non-White and older; those not passing milestone 2 were less likely to have insurance or a primary care physician; and those not passing milestone 3 were less educated, more likely to be bisexual as opposed to gay, more likely to live in the Midwest, had fewer male partners in the past year, and less likely to have tested for HIV in the past year. Effect sizes for significant findings were small. We successfully enrolled a national sample of HIV-negative GBM who completed at-home CASI assessments and at-home self-administered HIV and urine and rectal STI testing. This indicates high feasibility and acceptability of incorporating self-administered biological assays into otherwise fully online studies. Differences in completion of study milestones indicate a need for further investigation into the reasons for lower engagement by certain groups. PMID- 26858779 TI - Magnetic Resonance Imaging Perception of the Society in Kars: A Local Study. AB - BACKGROUND: The start point of this study was the sentence that a patient used: 'my pains had gone with MRI'. It is known that MRI has not a usage area in treatment, yet. Perhaps, the feeling of loss of pain was only a perception. But we want to search the demographic factors that make the perception of loss of pain. The purpose of this study was to determine the consciousness level of the society about MRI. MATERIAL/METHODS: This prospective survey study included 302 (107 men, 195 women; mean age 43.11+/-15.18 years) patients who were referred to the radiology clinic to undergo MRI. RESULTS: Almost half of the patients were illiterate and graduated from a primary school. Low level of education was more frequent in women than in men. Most of the patients declared that MRI would diagnose their disease. Among all the patients surveyed, 209 of 302 patients indicated no changes in the degree of pain before and after MRI, 30 indicated increased pain, 62 indicated decreased pain, and one patient did not answer the question. Most of the patients who declared decreasing pain had lumbar or cervical MRI. CONCLUSIONS: The function of MRI was known by the patients independently from their educational status. The degree of decrease in pain was higher in the 'treatment' answer. Perhaps the relatively higher percentage was a result of the expectations about treatment and was related with psychological motivation. PMID- 26858778 TI - In Vivo CT Direct Volume Rendering: A Three-Dimensional Anatomical Description of the Heart. AB - BACKGROUND: Since cardiac anatomy continues to play an important role in the practice of medicine and in the development of medical devices, the study of the heart in three dimensions is particularly useful to understand its real structure, function and proper location in the body. MATERIAL/METHODS: This study demonstrates a fine use of direct volume rendering, processing the data set images obtained by Computed Tomography (CT) of the heart of 5 subjects with age range between 18 and 42 years (2 male, 3 female), with no history of any overt cardiac disease. The cardiac structure in CT images was first extracted from the thorax by marking manually the regions of interest on the computer, and then it was stacked to create new volumetric data. RESULTS: The use of a specific algorithm allowed us to observe with a good perception of depth the heart and the skeleton of the thorax at the same time. Besides, in all examined subjects, it was possible to depict its structure and its position within the body and to study the integrity of papillary muscles, the fibrous tissue of cardiac valve and chordae tendineae and the course of coronary arteries. CONCLUSIONS: Our results demonstrated that one of the greatest advantages of algorithmic modifications of direct volume rendering parameters is that this method provides much necessary information in a single radiologic study. It implies a better accuracy in the study of the heart, being complementary to other diagnostic methods and facilitating the therapeutic plans. PMID- 26858781 TI - Ureteroscopy with conscious sedation for distal ureteric calculi: 10-year experience. AB - INTRODUCTION: Distal ureteroscopy for stone extraction is a common procedure that is generally performed with spinal or general anesthesia. We retrospectively reviewed all distal ureteroscopy performed for ureteric stone extraction with conscious sedation at our institution over a 10-year period to determine its efficacy and safety. METHODS: A retrospective chart review was performed of all distal ureteroscopy performed for calculus removal from 2004 to 2014. Patient characteristics, analgesic requirement, tolerability, procedure time, stone size and composition, method of stone extraction, success rate, and complications were collected. RESULTS: Between 2004 and 2014, 314 procedures were performed. Mean age was 53.74 years, with 160 males and 154 females. A success rate of 97% and 10 (3.2%) complications were reported. Mean analgesic requirement was 189 MUg of fentanyl (range: 50-400) and 2.79 mg of midazolam (range: 0-8). A total of 263 patients (83.7%) tolerated the procedure well, with only seven (2.2%) having poor tolerability. When comparing females to males, females were found to require less fentanyl (p=0.0001) and midazolam (p=0.0001). When calculi >5 mm were compared to those <5 mm, there was no statistically significant difference in success rate, procedure time, analgesic requirement, tolerability, or complications. CONCLUSION: Distal ureteroscopy with conscious sedation is safe and efficacious. To our knowledge, this is the first report demonstrating stones >5 mm can be safely and effectively treated with conscious sedation during this procedure. The context of our findings must be understood within the limitations of our retrospective analysis. PMID- 26858780 TI - Benefits of mesenchymal stem cells after partial bladder outlet obstruction. AB - INTRODUCTION: Partial bladder outlet obstruction (pBOO) results in significant morbidity and mortality in the pediatric and adult populations. Mesenchymal stem cells (MSC) have been widely studied in many organ systems for the treatment and prevention of fibrotic and inflammatory conditions. Therefore, we hypothesize that systemic administration of MSC will demonstrate short-term biochemical, histological, and urodynamic benefits in an animal model for pBOO. METHODS: After University ethics approval, 5 * 106 green fluorescent protein GFP-labeled MSC were intravenously injected concurrently with pBOO in adult Sprague-Dawley rats. Five groups (n=3/group) were analyzed: a) unobstructed controls; b) pBOO for seven days with intravenous MSC (7d+MSC); c) pBOO for seven days without intravenous MSC (7d-MSC); d) pBOO for 14 days with intravenous MSC (14d+MSC), e) pBOO for 14 days without MSC (14d-MSC). Urodynamics were performed at the end of the experimental period and bladders were weighed. Immunohistochemistry was performed for GFP detection and reverse transcription polymerase chain reaction (RT-PCR) to detect mRNA of: TGF-B, HIF-1a, RhoA, GRP-78, lumican, and decorin. RESULTS: All animals remained healthy. GFP was detected in all treatment groups. MSC treatment resulted in a significant decrease in bladder capacity (0.91 cc vs. 2.15 cc, p=0.04). Treatment also resulted in significant decreases in mRNA levels of: TGF-B, HIF-1a, Rho-A, and GRP-78. CONCLUSIONS: Systemic treatment with MSC was well tolerated and resulted in MSC accumulation after pBOO. Despite our low numbers, we were able to successfully demonstrate short-term urodynamic improvements and widespread, significant decreases in inflammatory mediators. We believe that this decreased inflammatory cascade will help prevent long-term detrusor deterioration. PMID- 26858782 TI - Predictors of time to biochemical recurrence in a radical prostatectomy cohort within the PSA-era. AB - INTRODUCTION: We sought to determine predictors for early and late biochemical recurrence following radical prostatectomy among localized prostate cancer patients. METHODS: The study included localized prostate cancer patients treated with radical prostatectomy (RP) at the University of Southern California from 1988 to 2008. Competing risks regression models were used to determine risk factors associated with earlier or late biochemical recurrence, defined using the median time to biochemical recurrence in this population (2.9 years after radical prostatectomy). RESULTS: The cohort for this study included 2262 localized prostate cancer (pT2-3N0M0) patients who did not receive neoadjuvant or adjuvant therapies. Of these patients, 188 experienced biochemical recurrence and a subset continued to clinical recurrence, either within (n=19, 10%) or following (n=13, 7%) 2.9 years after RP. Multivariable stepwise competing risks analysis showed Gleason score >=7, positive surgical margin status, and >=pT3a stage to be associated with biochemical recurrence within 2.9 years following surgery. Predictors of biochemical recurrence after 2.9 years were Gleason score 7 (4+3), preoperative prostate-specific antigen (PSA) level, and >=pT3a stage. CONCLUSIONS: Higher stage was associated with biochemical recurrence at any time following radical prostatectomy. Particular attention may need to be made to patients with stage >=pT3a, higher preoperative PSA, and Gleason 7 prostate cancer with primary high-grade patterns when considering longer followup after RP. PMID- 26858783 TI - Leak point pressure at different bladder volumes in stress urinary incontinence in women: Comparison between Valsalva and cough-induced leak point pressure. AB - INTRODUCTION: We compared Valsalva leak point pressure (VLPP) in urodynamically proven stress urinary incontinence (SUI) in women at different bladder volumes; examined the relationship between VLPP and cough-induced leak point pressure (CLPP) compared by incontinence severity; and evaluated the influence of bladder volume on each leak point pressure (LPP). METHODS: Women with urodynamically proven SUI who underwent serial VLPP and CLPP measurement at bladder volumes of 150, 200, 250, and 300 mL were included in this study (n=228). LPP determination was repeated two times in each subject after finishing one series of LPP measurement. LPP at different bladder volumes was compared by subjective symptom severity of Stamey grade. RESULTS: Patients mean age was 51.3+/-7.6 years (range: 40-65 years). Stamey grade I, II, and III was assigned to 68 (29.8%), 102 (44.7%), and 58 (25.4%) patients, respectively. Mean CLPP was higher than VLPP (p=0.002) at every bladder volume. VLPP and CLPP were significantly decreased by the increase of bladder volume (p=0.001). The mean first positive LPPs were significantly lower at higher Stamey grade (p=0.004). CONCLUSIONS: LPP is more frequently induced by cough than by the Valsalva maneuver. VLPP and CLPP decreased significantly with bladder filling and those with severe symptoms of SUI are more likely to have low LPP. PMID- 26858785 TI - A new technique to prevent curling of guide wire in urinary bladder during J stent insertion with flexible cystoscope. AB - Insertion of J stent is a very common procedure performed by urologists. This procedure is often performed to relieve ureteral obstruction due to stones, tumours, ureteral kink, or stricture on urgent basis. An increasing number of urologists are using a flexible cystoscope and local anaesthetic for J stent insertion. Occasionally, the guide wire curls in the bladder, making it impossible to insert the J stent. Here, we describe a simple method to overcome this problem using modified ureteral dilator, which is usually available in the cystoscopy suite. PMID- 26858784 TI - The role of renal biopsy in small renal masses. AB - Renal biopsy is being increasingly proposed as a diagnostic tool to characterize small renal masses (SRM). Indeed, the wide adoption of imaging in the diagnostic workup of many diseases had led to a substantial increased incidence of SRM (diameter <=4 cm). While modern ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) techniques have high sensitivity for detecting SRM, none is able to accurately and reliably characterize them in terms of histological features. This is currently of key importance in guiding clinical decision-making in some situations, and in these cases renal biopsy should be considered. In this review, we aim to summarize the technique, diagnostic performance, and predicting factors of nondiagnostic biopsy, as well as the future perspectives. PMID- 26858786 TI - Xanthogranulomatous pyelonephritis presenting as a pseudotumour. AB - INTRODUCTION: Xanthogranulomatous pyelonephritis (XGPN) is an atypical form of chronic pyelonephritis referred to as the "great imitator" because the clinical and radiological findings closely resemble other pathological entities, especially for the focal forms. Distinguishing focal XGPN from renal cancer is preoperatively difficult. METHODS: We report a total number of 12 pseudotumoural XGPN cases diagnosed and treated in our department. The aim of this study is to try to better understand the clinicopathological profile of XGPN and improve its management. RESULTS: The mean age of patients was 51.52 years. Gender ratio was 0.71. An obstructive renal calculus was noticed in nine patients (75%). Only one patient (8.3 %) presented with loin pain associated with fever, weight loss, asthenia, and increased biological inflammation markers. A bifocal mass was noticed in one case (8.3 %). The average size of the tumour was 6.58 cm. The mass was cystic in three cases (25 %). Perinephral fat strand, thickening of Gerota's fascia, hydronephrosis, and presence of renal calculi was noticed in all solid tumour cases. XGPN was suspected in only one case (8.3%), a percutaneous biopsy showed XGPN lesions treated by antibiotics and a double J drainage. Radical nephrectomy was performed in eight patients (66.7 %) and three patients underwent partial nephrectomy (25 %). No recurrence of XGPN has been noted. CONCLUSION: Pseudotumoural XGPN is a rare benign disease of the kidney. Its treatment should be conservative. Lack of knowledge of this disease may explain the high rate of abusive nephrectomies. These data should be considered in the future. PMID- 26858787 TI - Effect of ADMA levels on severity of erectile dysfunction in chronic kidney disease and other risk factors. AB - INTRODUCTION: Hormonal, neurogenic, vasculogenic, and psychogenic impairments, as well as endothelial dysfunction may play a role in erectile dysfunction (ED) in patients with chronic kidney disease (CKD). Asymmetrical dimethylarginine (ADMA) is an inhibitor of nitric oxide, which is the key element of ED. ADMA levels are increased in CKD. We aimed to evaluate the effect of serum ADMA, prolactin, testosterone, and hemoglobin levels on erectile function of patients with CKD and control subjects. METHODS: A total of 42 men with CKD and 25 age-matched controls were enrolled. The patients with CKD were categorized into group 1 and group 2 based on whether they had ED according to their response to International Index of Erectile Function questionnaire (IIEF-EFD). Group 3 was a control group. Serum ADMA, total testosterone prolactin, and hemoglobin levels of the patients were evaluated. RESULTS: Serum ADMA, testosterone, and hemoglobin levels were similar between group 1 and 2, serum prolactin level was significantly high in group 1 than in group 2 or 3 (control group). There was no correlation between ADMA levels and IIEF-EFD scores of patients with CKD. CONCLUSIONS: The results of this study suggest serum ADMA level is not related with ED in patients with CKD. Also, low testosterone and hemoglobin levels were not significant factors. High levels of serum prolactin are related with ED in patients with CKD. PMID- 26858788 TI - Changing of the guard? A glance at the surgical representation in the Canadian renal transplantation community. AB - INTRODUCTION: Renal transplant is the gold standard treatment for end-stage renal disease (ESRD), and the prevalence of both ESRD and renal transplant has been steadily increasing over the past decade. However, involvement of urology in renal transplant has been declining. We examine the current state of urology involvement in renal transplant programs across Canada. METHODS: A telephone survey of all surgical transplant centres in Canada was performed. Information regarding the number of transplant surgeons, their individual training background, and their involvement in specific procedures, including open and laparoscopic living donor nephrectomy, deceased donor nephrectomy, and recipient renal transplant were collected. RESULTS: There are 59 Canadian transplant surgeons, including 27 (46%) who completed a urology residency and 32 (54%) with a general surgery background. With regards to procedures performed, 58 (98%) perform recipient renal transplant surgery, 36 (61%) perform laparoscopic donor nephrectomy, and 17 (29%) perform open donor nephrectomy. There was no significant difference in the number of surgeons that perform renal recipient surgery, laparoscopic or open donor nephrectomies, and deceased donor nephrectomies between surgeons of the two different training backgrounds. CONCLUSIONS: The role of urology in Canadian renal transplant has declined significantly over the past decade. Given the medical and surgical complexity of renal transplant, along with the growing need for renal transplants, a multidisciplinary team approach is imperative. Strong urology involvement with the transplant team is crucial for optimal care of these complex patients. PMID- 26858789 TI - Current Chemotherapy and Potential New Targets in Uterine Leiomyosarcoma. AB - A variety of chemotherapeutic agents have been used for treating recurrent or advanced stage uterine leiomyosarcoma (ULMS). The response rates of these current agents are disappointing, with partial response rates varying from 0% to 33%, and complete response rates varying from 0% to 8%. Recent studies have documented many molecular changes in ULMSs. Prominent amongst these are gains of growth factors C-MYC, Bcl-2, K-ras, and Ki-67, and losses in tumor suppressors p16, p53, Rb1, ING2 and D14S267. Various techniques that have been used to target these molecules are presented. Targeting specific therapies at these underlying molecular changes could potentially yield better response rates with fewer side effects. PMID- 26858790 TI - Tissue Plasminogen Activator Use in Cardiac Arrest Secondary to Fulminant Pulmonary Embolism. AB - BACKGROUND: Tissue plasminogen activator (tPA) is used emergently to dissolve thrombi in the treatment of fulminant pulmonary embolism. Currently, there is a relative contraindication to tPA in the setting of traumatic or prolonged cardiopulmonary resuscitation > 10 minutes because of the risk of massive hemorrhage. METHODS: Our single-center, retrospective study investigated patients experiencing cardiac arrest (CA) secondary to pulmonary embolus. We compared the effectiveness of advanced cardiac life support with the administration of tPA vs. the standard of care consisting of advanced cardiac life support without thrombolysis. The primary endpoint was survival to discharge. Secondary endpoints were return of spontaneous circulation (ROSC), major bleeding, and minor bleeding. RESULTS: We analyzed 42 patients, of whom 19 received tPA during CA. Patients who received tPA were not associated with a statistically significant increase in survival to discharge (10.5% vs. 8.7%, P = 1.00) or ROSC (47.4% vs. 47.8%, P = 0.98) compared to the control group. We observed no statistically significant difference between the groups in major bleeding events (5.3% in the tPA group vs. 4.3% in the control group, P = 1.00) and minor bleeding events (10.5% in the tPA group vs. 0.0% in the control group, P = 0.11). CONCLUSION: This study did not find a statistically significant difference in survival to discharge or in ROSC in patients treated with tPA during CA compared to patients treated with standard therapy. However, because no significant difference was found in major or minor bleeding, we suggest that the potential therapeutic benefits of this medication should not be limited by the potential for massive hemorrhage. Larger prospective studies are warranted to define the efficacy and safety profile of thrombolytic use in this population. PMID- 26858791 TI - Seropositivity for West Nile Virus Antibodies in Patients Affected by Myasthenia Gravis. AB - BACKGROUND: Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal muscles. Specific auto-antibodies against acetylcholine receptor (AChR) are present in the majority of MG patients, although the main cause behind its development still remains unclear. Recently MG development following West Nile virus (WNV) infection has been described in patients without any earlier evidence of MG. It is known that infectious agents trigger immune response and occasionally initiate autoimmune disease. WNV, the causative agent of both benign illness and neuroinvasive disease, has become endemic in many countries in all continents. METHODS: In the present study, 29 patients (15 males and 14 females, 19 - 78 years old) with confirmed diagnosis of MG and elevated levels of AChR autoantibodies were screened for the presence of serum anti-WNV antibodies and compared to a similar population affected by different autoimmune diseases. Indirect immunofluorescent antibody technique was used to evaluate the reaction of patients' sera on cells infected by WNV. RESULTS: Positive fluorescent signals for anti-WNV IgG were obtained in 17% of MG patients, although no clinical manifestations related to WNV infection were reported. These results are in agreement with previous data and appear of great interest in the understanding of the pathogenic autoimmune mechanisms at the bases of MG development. CONCLUSION: As already observed in other human autoimmune diseases, pathogen-triggered autoimmunity could be involved in MG by breaking immunological self-tolerance through possible mechanisms of molecular mimicry between virus proteins and AChR subunits. In predisposed individuals, WNV infection could also represent an additional risk factor to initiate MG. PMID- 26858792 TI - Temperament and Character Profiles and Psychiatric Comorbidities in Patients With Coronary Artery or Valvular Heart Disease: Relationship With Cardiac Disease Severity. AB - BACKGROUND: We aimed to investigate whether the psychopathological symptoms and temperament-character dimensions observed in patients operated due to coronary artery disease (CAD) or valvular heart disease (VHD) differ among the patients and from healthy individuals. METHODS: Study population was composed of subjects with CAD, VHD and healthy controls (n = 50 in each group). Socio-demographic questionnaire, temperament and character inventory (TCI) and symptom check list 90-R (SCL-90-R) were applied to all groups. Groups were compared about temperament-character dimensions and scores of subscales of SCL-90-R. RESULTS: Harm avoidance was found to be higher in VHD group than those with CAD and, lower in healthy controls than both patient groups (P = 0.004). Reward dependence was similar among both patient groups and, was higher than healthy group (P = 0.015). Depression, anxiety, somatization, obsession and interpersonal sensitivity were found to be similar in both patient groups but they were higher than those in controls (P < 0.001, P < 0.001, P < 0.001, P = 0.002 and P = 0.003, respectively). Phobia was seen equally in CAD group and healthy controls and, was found to be lower in these than in VHD (P = 0.009). Anger score was in descending order in patients with VHD, CAD and healthy controls group (P = 0.010 and 0.001). Paranoia was in descending order in patients with VHD, CAD and controls (P = 0.015 and 0.001). A weak and inverse correlation was found between ejection fraction (EF) and the persistence dimension of temperament scaled by TCI in patients with VHD (r = -0.276, P = 0.052). An inverse correlation was observed between EF and the reward dependence dimension in CAD group (r = -0.195, P = 0.044). In patients with VHD, EF demonstrated an inversely weak (r = -0.289, P = 0.042), moderate (r = -0.360, P = 0.010) and strong (r = -0.649, P < 0.001) correlation with inter-personal sensitivity, phobia and paranoia, respectively. There was an inverse and weak correlation between EF and depression and anger in VHD group (r = -0.302, P = 0.033 and r = -0.240, P = 0.054). CONCLUSION: VHD and CAD exhibit different psychopathological symptoms and temperament traits. There is a correlation between the aforementioned psychopathological symptoms and temperament traits, and EF. PMID- 26858793 TI - The MacNew Questionnaire Is a Helpful Tool for Predicting Unplanned Hospital Readmissions After Coronary Revascularization. AB - BACKGROUND: The MacNew questionnaire is a neuro-behavioral tool which is easy and immediately usable. This self-reported questionnaire filled out by the patient allows the physician to achieve helpful information concerning the ways for optimizing the therapy and patient's lifestyles. In this retrospective study, our aim was to assess whether relatively high scores found using the MacNew questionnaire in patients who had undergone percutaneous or surgical revascularization were associated with a decreased risk of unscheduled hospitalizations during the follow-up. METHODS: A retrospective analysis concerning 210 patients was carried out. The clinical sheets of these patients were examined as regards the information provided in the specific questionnaires (MacNew Italian version) routinely administered during the hospitalization prescribed for recovering from recent interventions of coronary percutaneous or surgery revascularization. Every patient undergoing the psychological test with MacNew questionnaire was followed up for 3 years. RESULTS: Using univariate analysis, a global score's high value (i.e., above the median of the whole examined population) was shown to be associated with a significantly decreased risk of rehospitalization (HR (hazard ratio): 0.4312; 95% CI: 0.3463 - 0.5370; P < 0.0001). After adjustment for age, gender and myocardial infarction as initiating event, using a multivariate Cox proportional hazards regression model, the protection exerted by a high MacNew score against the risk of hospitalizations remained significant (HR: 0.0885; 95% CI: 0.0317 - 0.2472; P < 0.0001). CONCLUSIONS: A relatively elevated MacNew global score appears to be associated with a significantly decreased risk of unscheduled hospitalizations after coronary revascularization over a 3-year follow-up. PMID- 26858794 TI - Epicardial Adipose Tissue Thickness in Patients With Subclinical Hypothyroidism and the Relationship Thereof With Visceral Adipose Tissue Thickness. AB - BACKGROUND: Subclinical hypothyroidism (SH) is associated with cardiovascular metabolic syndromes, especially dislipidemia and abdominal obesity. Visceral abdominal adipose tissue (VAAT) and epicardial adipose tissue (EAT) have the same ontogenic origin and produce many proinflammatory and proatherogenic cytokines. We evaluated EAT and VAAT thickness in patients with SH. METHODS: Forty-one patients with SH and 35 controls were included in the study. Demographical and anthropometric features of both patients and controls were recorded. Thyroid and metabolic parameters were measured. EAT was measured using 2D-transthoracic echocardiography. RESULTS: The age and gender distributions were similar in the two groups (P = 0.998 and P = 0.121, respectively). Body mass index (BMI), fat mass, waist circumference (WC), hip circumference (HC), the WC/HC ratio, and the thicknesses of VAAT and abdominal subcutaneous adipose tissue were higher in the case group than the control group (all P values < 0.01). However, both groups had similar EAT thickness (P = 0.532), which was positively correlated with BMI, fat mass, WC, HC, VAAT thickness, abdominal subcutaneous adipose tissue thickness, and serum triglyceride (TG) level (all P values < 0.01). We found no correlation between EAT thickness and thyroid-stimulating hormone (TSH) level, free thyroxine (FT4) level, or low-density lipoprotein-cholesterol (LDL-C) level, and anti-TPO level (all P values > 0.05). We found no difference between the two groups in fasting plasma glucose (FPG) level (P = 0.780), but the levels of LDL-C and TG differed significantly (P = 0.002 and P = 0.026, respectively). The serum TSH level was higher and the FT4 level was lower in the case than the control group (both P values <0.01). CONCLUSION: Increased abdominal adipose tissue thickness in patients with SH is associated with atherosclerosis. To detemine the risk of atherosclerosis in such patients, EAT measurements are valuable; such assessment is simple to perform. PMID- 26858795 TI - Effects of Obstructive Sleep Apnea Hypopnea Syndrome on Blood Pressure and C Reactive Protein in Male Hypertension Patients. AB - BACKGROUND: The influences of obstructive sleep apnea hypopnea syndrome (OSAHS) on blood pressure and C-reactive protein (CRP) were observed, and the underlying mechanism was investigated. METHODS: Respiratory sleep monitoring was performed on 188 male patients who were newly diagnosed with hypertension. Based on the apnea hypopnea index (AHI) results, patients were divided into a normal control group (AHI <= 5, n = 35), a mild OSAHS group (5 < AHI <= 15, n = 28), a moderate OSAHS group (15 < AHI <= 30, n = 57), and a severe OSAHS group (AHI > 30, n = 68). Ambulatory blood pressure monitoring was conducted on patients in each group, and blood samples were collected to detect indicators, including fasting blood glucose (FBG), triglyceride (TG), low-density lipoprotein-cholesterol (LDL C), high-density lipoprotein-cholesterol (HDL-C), and high-sensitivity CRP (hs CRP). RESULTS: TG and hs-CRP in patients in the moderate and severe OSAHS groups were higher than those in the normal control group (P < 0.01, P < 0.05). Additionally, their mean nocturnal systolic blood pressure (nSBP) and nocturnal diastolic blood pressure (nDBP) were higher than those in the normal control group (P < 0.01, P < 0.05). However, the percentage of blood pressure reduction at night was significantly lower than that in the normal control group (P < 0.01). AHI and hs-CRP positively correlated with nSBP (adjusted R(2) = 0.46) and nDBP (adjusted R(2) = 0.38) and negatively correlated with the nocturnal blood pressure reduction percentage (adjusted R(2) = 0.48). CONCLUSION: Moderate and severe OSAHS induced increases in nocturnal blood pressure and CRP content in the body, resulting in further damage to the circadian rhythms of blood pressure. PMID- 26858797 TI - High Seroprevalence of Leptospira Exposure in Meat Workers in Northern Mexico: A Case-Control Study. AB - BACKGROUND: The seroepidemiology of Leptospira infection in workers occupationally exposed to raw meat has been poorly studied. This work aimed to determine the association between Leptospira exposure and the occupation of meat worker, and to determine the seroprevalence association with socio-demographic, work, clinical and behavioral characteristics of the meat workers studied. METHODS: We performed a case-control study in 124 meat workers and 124 age- and gender-matched control subjects in Durango City, Mexico. Sera of cases and controls were analyzed for anti-Leptospira IgG antibodies using a commercially available enzyme immunoassay. Data of meat workers were obtained with the aid of a questionnaire. The association of Leptospira exposure with the characteristics of meat workers was analyzed by bivariate and multivariate analyses. RESULTS: Anti-Leptospira IgG antibodies were found in 22 (17.7%) of 124 meat workers and in eight (6.5%) of 124 controls (OR = 3.12; 95% CI: 1.33 - 7.33; P = 0.006). Seroprevalence of Leptospira infection was similar between male butchers (17.6%) and female butchers (18.2%) (P = 1.00). Multivariate analysis of socio demographic, work and behavioral variables showed that Leptospira exposure was associated with duration in the activity, rural residence, and consumption of snake meat and unwashed raw fruits. CONCLUSIONS: This is the first case-control study of the association of Leptospira exposure with the occupation of meat worker. Results indicate that meat workers represent a risk group for Leptospira exposure. Risk factors for Leptospira exposure found in this study may help in the design of optimal preventive measures against Leptospira infection. PMID- 26858796 TI - Scintigraphic Evaluation of the Stump Region After Extremity Amputation and the Effect of Scintigraphy on Treatment. AB - BACKGROUND: We evaluated the stump region with scintigraphy and compared the correlation of treatment modalities and scintigraphic results. METHODS: Sixty eight cases with extremity amputation were included in the study. Amputation applied cases underwent four-phase Tc-99m hydroxymethylene diphosphonate scintigraphy. Groups were performed according to the scanning time after amputation and amputation regions. After scintigraphic evaluation, results were recorded into five groups: osteomyelitis, soft-tissue infection, reactive changes secondary to surgery, chronic osteomyelitis, and normal. Post-surgical treatment modalities of the patients were determined and compared with scintigraphic results. RESULTS: In the scintigraphic evaluation of stump regions of the 68 amputated cases, 34 patients had acute osteomyelitis, one had chronic osteomyelitis, 16 had soft-tissue infection, and eight had changes secondary to the surgery. Nine of 68 cases had normal scintigraphic features. In the scintigraphic evaluation, 43 patients took antibiotic treatment and 16 had surgery. There was a strong correlation between scintigraphic results and treatment approach (P < 0.0001, r = 0.803) by means of preferred therapy and effectiveness of the therapy according to the scintigraphic results. Scintigraphy need increases with age after amputation and a negative correlation between patient age and scintigraphic need was found (P < 0.02, r = -0.339). There was no pathology in the follow-up in the cases that were scintigraphically normal. CONCLUSION: Bone scintigraphy is a cost-effective, non-invasive, and efficient method that directs treatment in the evaluation of the stump region after amputation. PMID- 26858798 TI - Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Metabolic Parameters in Patients With Type 2 Diabetes: A Chart-Based Analysis. AB - BACKGROUND: Effects of the new class of anti-diabetic drugs, sodium-glucose cotransporter 2 (SGLT2) inhibitors, on metabolic parameters in patients with type 2 diabetes remain largely unknown. METHODS: We retrospectively picked up patients who had been continuously prescribed SGLT2 inhibitors for 1 month or more between April 2014 and November 2015 by a chart-based analysis, and compared the data before the SGLT2 inhibitor treatment with the data at 1, 2, 3 and 6 months after the SGLLT2 inhibitor treatment started. RESULTS: Fifty patients were eligible for the analyses in our study. The HbA1c levels as well as body weight significantly decreased at 1, 2, 3 and 6 months after the start of SGLT2 inhibitors. Systolic blood pressure tended to decrease only at 1 and 2 months, but there was no change at 3 and 6 months. No significant change was observed in serum high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and non-HDL-C levels. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels significantly decreased at 3 and 6 months after the prescription. The hematocrit levels significantly increased at 1, 2, 3 and 6 months, and the estimated glomerular filtration rate (eGFR) levels significantly decreased at 1 month after the start of SGLT2 inhibitors. A significant correlation between reductions in HbA1c levels and HbA1c levels at baseline was observed at 1, 3 and 6 months. The decreases in serum ALT levels were also significantly correlated with the baseline ALT levels at 3 and 6 months. CONCLUSION: Present study demonstrated that SGLT2 inhibitors significantly reduced HbA1c and body weight and improved liver functions, whereas no significant change was observed in serum lipid profiles. PMID- 26858799 TI - History of Assisted Reproductive Technology and Chlamydia Trachomatis Infection in Pregnancy. AB - BACKGROUND AND METHODS: To identify whether or not a history of assisted reproductive technology (ART) is associated with the low incidence of Chlamydia trachomatis (CT) infection in pregnant women, we reviewed the obstetric records of the Japanese women aged 35 - 42 years. RESULTS: The prevalence of CT in the pregnancies without ART was 1.1% (28/2,632) using nucleic acid amplification tests, while it was zero in the pregnancies conceived by ART (0/364, P = 0.049 by the X(2) test). CONCLUSIONS: A history of ART seemed to be a negative risk factor for CT infection in pregnant women. PMID- 26858800 TI - The Diversity of the Clinical Phenotypes in Patients With Fibrodysplasia Ossificans Progressiva. AB - BACKGROUND: The clinical presentation, phenotypic characterization and natural history of fibrodysplasia ossificans progressiva (FOP) are diverse and the natural history of the disease is, to a certain extent, different from one patient to another. METHODS: In a series of 11 patients (eight girls and three boys, aged 0 - 16 years), variable clinical presentations were the landmarks of these patients. At birth, all of our patients manifested short great toes in a valgus position. Marfan syndrome was the suggested diagnosis in three children aged 3 - 8 years and in two pre-adult patients. Clinical symptoms were torticollis, painful spine, and painful and marked limitation of the pelvic movements. Monophalangia associated with Marfanoid habitus was also a prevailing clinical presentation. RESULTS: Our results were based upon the appearance of the earliest pathologic feature of FOP in correlation with the clinical presentation. In infants (0 - 1 year), three infants showed congenital hallux valgus and stiff spine. In the pediatric group (3 - 8 years), all children showed no mutation in the fibrillin-1 (FBN1) gene. Their prime presentation was a progressive torticollis with simultaneous development of erythematous subfascial nodules, most commonly located on the posterior neck and back. In pre-adult group (10 - 16 years), four patients presented with monophalangia associated with painful movements because of the progressive heterotopic ossification of the spine and the weight bearing zones and marked elevation of alkaline phosphatase. Genetic confirmation has been performed in six patients who manifested the classical mutation of the ACVR1 gene. The rest of the patients were assessed via clinical and radiographic phenotypes. CONCLUSION: The early recognition of FOP can be performed by noticing the short halluces and thumbs at early infancy and later on the high alkaline phosphatase activity in areas of heterotopic ossification. Misconception of FOP is of common practice and eventually unnecessary diagnostic biopsies might deteriorate the progression of the condition. The detection of ACVR1 gene mutation was a confirmatory procedure. Interestingly, the timing of the onset and the location of progressive heterotopic ossifications were extremely variable and confusing among our group of patients. PMID- 26858801 TI - Histoplasma capsulatum: An Unusual Case of Pericardial Effusion and Coarctation of the Aorta. AB - Histoplasma capsulatum is a fungus that is endemic in many parts of the world and can present with a wide variety of symptoms. Here we present a case of a previously healthy 19-year-old female who presented with shortness of breath. She was found to have a right lung mass and coarctation of the aorta on computed tomography imaging. Pathology revealed granuloma caused by Histoplasma capsulatum. She later developed massive pericardial effusion, requiring emergent pericardiocentesis. She was treated with anti-fungal therapy and recovered well. This case illustrates an unusual presentation of newly diagnosed coarctation of the aorta complicated by Histoplasma pericardial effusion. Imaging and pathology slides are reviewed. PMID- 26858802 TI - An Avid Imitator. AB - We present a case of disseminated cryptococcal disease, coexisting with and mimicking lymphoma. Determination of serum cryptococcal antigen should be considered for lymphopenic patients with hematologic malignancies, presenting with unexplained fever, and/or lymphadenopathy and/or pulmonary findings. Patients with hematologic malignancies treated with chemotherapy regimens are susceptible to diverse opportunistic infections. Therefore, in this patient population, it is often necessary to obtain a definitive pathologic diagnosis, to diagnose uncommon syndromes and guide management. PMID- 26858803 TI - Spontaneous Pneumothorax With Subcutaneous Emphysema: A Rare Complication of Respiratory Syncytial Virus Infection. AB - Viral bronchiolitis is the most common lower respiratory tract infection in infants and children under the age of 2. Respiratory syncytial virus (RSV) is the infecting agent in more than 50% of the cases. Usually the clinical course is uneventful and complications are uncommon. Secondary air leaks are a recognized rare complication of bronchiolitis, although the real incidence remains unknown. We report a case of a 21-month-old female that developed a spontaneous pneumothorax (PNO) with subcutaneous emphysema (SE) late in the course of RSV acute bronchiolitis. Additional investigation ruled out any underlying disease predisposing to spontaneous PNO. Physicians, especially those who work with small children, must be aware of this uncommon complication of bronchiolitis that may appear late in the course of the disease despite an initial clinical improvement. PMID- 26858804 TI - Posterior Reversible Encephalopathy Syndrome Resolving Within 48 Hours in a Normotensive Patient Who Underwent Thoracic Spine Surgery. AB - Posterior reversible encephalopathy syndrome (PRES) usually manifests with severe headaches, seizures, and visual disturbances due to uncontrollable hypertension. A patient (age in the early 60s) with a history of renal cell cancer presented with lower-extremity weakness and paresthesias. Magnetic resonance imaging (MRI) of the thoracic spine revealed a T8 vertebral body metastatic lesion with cord compression at that level. The patient underwent preoperative embolization of the tumor followed by posterior resection and placement of percutaneous pedicle screws and rods. Postoperatively, the patient experienced decreased visual acuity bilaterally. Abnormal MRI findings consisted of T2 hyperintense lesions and fluid attenuated inversion recovery changes in both occipital lobes, consistent with the unique brain imaging pattern associated with PRES. The patient's blood pressure was normal and stable from the first day of hospitalization. The patient was kept on high-dose steroid therapy, which was started intraoperatively, and improved within 48 hours after symptom onset. PMID- 26858805 TI - Correction: Efficacy and Safety of Ipragliflozin in Japanese Patients With Type 2 Diabetes: Interim Outcome of the ASSIGN-K Study. AB - [This corrects the article DOI: 10.14740/jocmr2417w.]. PMID- 26858806 TI - Religion and HIV/AIDS Stigma: Considerations for the Nursing Profession. AB - Nurses' stigmatization of people living with HIV/AIDS hinders effective health care provisions for this sector of the population. Scientific literature on HIV/AIDS stigma has emphasized cognitive, individual, and interpersonal factors that are relevant to the understanding of the stigmatization process among health care professionals (e.g. a health care professional's accuracy in knowledge of the workings of the virus, effectiveness of emotion management, degree of proximity to the stigmatized group, etc.). However, researchers have also examined the socio-structural factors underlying stigma, and religion has consequently emerged as a social phenomenon that may foster it. The role of religion among professional nurses who specifically service people living with HIV/AIDS remains understudied. Focusing on evidence-based literature, we discuss the relationship between religion and HIV/AIDS stigma, explore potential implications of this relationship for the nursing profession, and make recommendations for stigma-reducing interventions. PMID- 26858807 TI - A highly efficient bead extraction technique with low bead number for digital microfluidic immunoassay. AB - Here, we describe a technique to manipulate a low number of beads to achieve high washing efficiency with zero bead loss in the washing process of a digital microfluidic (DMF) immunoassay. Previously, two magnetic bead extraction methods were reported in the DMF platform: (1) single-side electrowetting method and (2) double-side electrowetting method. The first approach could provide high washing efficiency, but it required a large number of beads. The second approach could reduce the required number of beads, but it was inefficient where multiple washes were required. More importantly, bead loss during the washing process was unavoidable in both methods. Here, an improved double-side electrowetting method is proposed for bead extraction by utilizing a series of unequal electrodes. It is shown that, with proper electrode size ratio, only one wash step is required to achieve 98% washing rate without any bead loss at bead number less than 100 in a droplet. It allows using only about 25 magnetic beads in DMF immunoassay to increase the number of captured analytes on each bead effectively. In our human soluble tumor necrosis factor receptor I (sTNF-RI) model immunoassay, the experimental results show that, comparing to our previous results without using the proposed bead extraction technique, the immunoassay with low bead number significantly enhances the fluorescence signal to provide a better limit of detection (3.14 pg/ml) with smaller reagent volumes (200 nl) and shorter analysis time (<1 h). This improved bead extraction technique not only can be used in the DMF immunoassay but also has great potential to be used in any other bead-based DMF systems for different applications. PMID- 26858808 TI - Magnetic microchains and microswimmers in an oscillating magnetic field. AB - Superparamagnetic micro-bead chains and microswimmers under the influence of an oscillating magnetic field are studied experimentally and numerically. The numerical scheme composed of the lattice Boltzmann method, immersed boundary method, and discrete particle method based on the simplified Stokesian dynamics is applied to thoroughly understand the interaction between the micro-bead chain (or swimmer), the oscillating magnetic field, and the hydrodynamics drag. The systematic experiments and simulations demonstrated the behaviors of the microchains and microswimmers as well as the propulsive efficiencies of the swimmers. The effects of key parameters, such as field strengths, frequency, and the lengths of swimmer, are thoroughly analyzed. The numerical results are compared with the experiments and show good qualitative agreements. Our results proposed an efficient method to predict the motions of the reversible magnetic microdevices which may have extremely valuable applications in biotechnology. PMID- 26858809 TI - Measurements of flow-induced birefringence in microfluidics. AB - In this study, we demonstrate the use of a microscopic circular polariscope to measure the flow-induced birefringence in a microfluidic device that represents the kinematics of fluid motion optically. Unlike the commercial birefringence microscope employed in the previous studies, our approach is able to provide direct measurement of retardance, which quantifies the difference in refractive index of the fluid experienced by the ordinary and extraordinary rays, from one single image frame. This capability facilitates unsteady full-field quantitation of flow-induced birefringence in microfluidics that has never been achieved before. At low flow rates, we find that the value of the retardance is independent of the microfluidic design and proportional to the nominal strain rates. This linearity bridges the measurement of birefringence and the deformation rate in the microflow environment, which yields the stress information of the fluid flow. In addition, the MUPIV results confirm that both extensional and shear strain rates contribute to the flow-induced birefringence so that the retardance distribution can be used to represent the field of the principal strain rate in a microfluidic device. The outcome of this study proves that our approach provides a non-invasive method that enables an intuitive full field representation of stress in the instantaneous flow field in a microfluidic device. PMID- 26858810 TI - Depth position detection for fast moving objects in sealed microchannel utilizing chromatic aberration. AB - This research reports a novel method for depth position measurement of fast moving objects inside a microfluidic channel based on the chromatic aberration effect. Two band pass filters and two avalanche photodiodes (APD) are used for rapid detecting the scattered light from the passing objected. Chromatic aberration results in the lights of different wavelengths focus at different depth positions in a microchannel. The intensity ratio of two selected bands of 430 nm-470 nm (blue band) and 630 nm-670 nm (red band) scattered from the passing object becomes a significant index for the depth information of the passing object. Results show that microspheres with the size of 20 MUm and 2 MUm can be resolved while using PMMA (Abbe number, V = 52) and BK7 (V = 64) as the chromatic aberration lens, respectively. The throughput of the developed system is greatly enhanced by the high sensitive APDs as the optical detectors. Human erythrocytes are also successfully detected without fluorescence labeling at a high flow velocity of 2.8 mm/s. With this approach, quantitative measurement for the depth position of rapid moving objects inside a sealed microfluidic channel can be achieved in a simple and low cost way. PMID- 26858811 TI - Polymer-based disposable microneedle array with insertion assisted by vibrating motion. AB - This work presents a disposable polymer-based microneedle array that carries out insertions by mimicking the vibrating motion of a mosquito's proboscis. The proposed device, which comprises a 10:1 high-aspect-ratio parylene microneedle array and a chamber structure, was monolithically realized using a novel fabrication process. The vibrating motion of the microneedles was generated using a piezoelectric actuator. This device can be potentially applied to extract and collect blood by puncturing the dermis layer of human skin. The fabricated device is advantageous because of its biocompatibility, simple fabrication process, and low associated costs. Additionally, the graph of the measured extraction flow rate versus the pressure drop that is presented shows an agreement with the results predicted by analytical models. A 40% reduction of insertion force was demonstrated when the microneedle insertion was assisted by actuator-induced vibratory motions. Buckling analyses for estimating the maximum loads that the microneedle can sustain before failure occurs were also evaluated. Finally, the relationship between the insertion force and the vibration frequency was demonstrated in this study. PMID- 26858812 TI - Enhancement of microfluidic particle separation using cross-flow filters with hydrodynamic focusing. AB - A microfluidic chip is proposed to separate microparticles using cross-flow filtration enhanced with hydrodynamic focusing. By exploiting a buffer flow from the side, the microparticles in the sample flow are pushed on one side of the microchannels, lining up to pass through the filters. Meanwhile a larger pressure gradient in the filters is obtained to enhance separation efficiency. Compared with the traditional cross-flow filtration, our proposed mechanism has the buffer flow to create a moving virtual boundary for the sample flow to actively push all the particles to reach the filters for separation. It further allows higher flow rates. The device only requires soft lithograph fabrication to create microchannels and a novel pressurized bonding technique to make high-aspect-ratio filtration structures. A mixture of polystyrene microparticles with 2.7 MUm and 10.6 MUm diameters are successfully separated. 96.2 +/- 2.8% of the large particle are recovered with a purity of 97.9 +/- 0.5%, while 97.5 +/- 0.4% of the small particle are depleted with a purity of 99.2 +/- 0.4% at a sample throughput of 10 MUl/min. The experiment is also conducted to show the feasibility of this mechanism to separate biological cells with the sample solutions of spiked PC3 cells in whole blood. By virtue of its high separation efficiency, our device offers a label-free separation technique and potential integration with other components, thereby serving as a promising tool for continuous cell filtration and analysis applications. PMID- 26858813 TI - Biomimetic channel modeling local vascular dynamics of pro-inflammatory endothelial changes. AB - Endothelial cells form the inner lining of blood vessels and are exposed to various factors like hemodynamic conditions (shear stress, laminar, and turbulent flow), biochemical signals (cytokines), and communication with other cell types (smooth muscle cells, monocytes, platelets, etc.). Blood vessel functions are regulated by interactions among these factors. The occurrence of a pathological condition would lead to localized upregulation of cell adhesion molecules on the endothelial lining of the blood vessel. This process is promoted by circulating cytokines such as tumor necrosis factor-alpha, which leads to expression of intercellular adhesion molecule-1 (ICAM-1) on the endothelial cell surface among other molecules. ICAM-1 is critical in regulating endothelial cell layer dynamic integrity and cytoskeletal remodeling and also mediates direct cell-cell interactions as part of inflammatory responses and wound healing. In this study, we developed a biomimetic blood vessel model by culturing confluent, flow aligned, endothelial cells in a microfluidic platform, and performed real time in situ characterization of flow mediated localized pro-inflammatory endothelial activation. The model mimics the physiological phenomenon of cytokine activation of endothelium from the tissue side and studies the heterogeneity in localized surface ICAM-1 expression and F-actin arrangement. Fluorescent antibody coated particles were used as imaging probes for identifying endothelial cell surface ICAM-1 expression. The binding properties of particles were evaluated under flow for two different particle sizes and antibody coating densities. This allowed the investigation of spatial resolution and accessibility of ICAM-1 molecules expressed on the endothelial cells, along with their sensitivity in receptor ligand recognition and binding. This work has developed an in vitro blood vessel model that can integrate various heterogeneous factors to effectively mimic a complex endothelial microenvironment and can be potentially applied for relevant blood vessel mechanobiology studies. PMID- 26858814 TI - Capillarity ion concentration polarization for spontaneous biomolecular preconcentration mechanism. AB - Ionic hydrogel-based ion concentration polarization devices have been demonstrated as platforms to study nanoscale ion transport and to develop engineering applications, such as protein preconcentration and ionic diodes/transistors. Using a microfluidic system composed of a perm-selective hydrogel, we demonstrated a micro/nanofluidic device for the preconcentration of biological samples using a new class of ion concentration polarization mechanism called "capillarity ion concentration polarization" (CICP). Instead of an external electrical voltage source, the capillary force of the perm-selective hydrogel spontaneously generated an ion depletion zone in a microfluidic channel by selectively absorbing counter-ions in a sample solution. We demonstrated a reasonable preconcentration factor (~100-fold/min) using the CICP device. Although the efficiency was lower than that of conventional electrokinetic ICP operation due to the absence of a drift ion migration, this mechanism was free from the undesirable instability caused by a local amplified electric field inside the ion depletion zone so that the mechanism should be suitable especially for an application where the contents were electrically sensitive. Therefore, this simple system would provide a point-of-care diagnostic device for which the sample volume is limited and a simplified sample handling is demanded. PMID- 26858815 TI - Centrifugal sedimentation immunoassays for multiplexed detection of enteric bacteria in ground water. AB - Waterborne pathogens pose significant threat to the global population and early detection plays an important role both in making drinking water safe, as well as in diagnostics and treatment of water-borne diseases. We present an innovative centrifugal sedimentation immunoassay platform for detection of bacterial pathogens in water. Our approach is based on binding of pathogens to antibody functionalized capture particles followed by sedimentation of the particles through a density-media in a microfluidic disk. Beads at the distal end of the disk are imaged to quantify the fluorescence and determine the bacterial concentration. Our platform is fast (20 min), can detect as few as ~10 bacteria with minimal sample preparation, and can detect multiple pathogens simultaneously. The platform was used to detect a panel of enteric bacteria (Escherichia coli, Salmonella typhimurium, Shigella, Listeria, and Campylobacter) spiked in tap and ground water samples. PMID- 26858816 TI - Continuous-wave laser generated jets for needle free applications. AB - We designed and built a microfluidic device for the generation of liquid jets produced by thermocavitation. A continuous wave (CW) laser was focused inside a micro-chamber filled with a light-absorbing solution to create a rapidly expanding vapor bubble. The chamber is connected to a micro-channel which focuses and ejects the liquid jet through the exit. The bubble growth and the jet velocity were measured as a function of the devices geometry (channel diameter D and chamber width A). The fastest jets were those for relatively large chamber size with respect to the channel diameter. Elongated and focused jets up to 29 m/s for a channel diameter of [Formula: see text] and chamber size of [Formula: see text] were obtained. The proposed CW laser-based device is potentially a compact option for a practical and commercially feasible needle-free injector. PMID- 26858817 TI - Uncertainty quantification in modeling of microfluidic T-sensor based diffusion immunoassay. AB - Comparison of experimental data with modeling predictions is essential for making quantitative measurements of species properties, such as diffusion coefficients and species concentrations using a T-sensor. To make valid comparisons between experimental data and model predictions, it is necessary to account for uncertainty in model predictions due to uncertain values of model parameters. We present an analysis of uncertainty induced in model predictions of a T-sensor based competitive diffusion immunoassay due to uncertainty in diffusion constants, binding reaction rate constants, and inlet flow speed. We use a non intrusive stochastic uncertainty quantification method employing polynomial chaos expansions to represent the dependence of uncertain species concentrations on the uncertainty in model parameters. Our simulations show that the uncertainties in model parameters lead to significant spatially varying uncertainty in predicted concentration. In particular, the diffusivity of fluorescently labeled probe antigen dominates the overall uncertainty. The predicted uncertainty in fluorescence intensity is minimum near the centerline of T-sensor and relatively high in the regions with gradients in fluorescence intensity. We show that using centerline fluorescence intensity instead of first derivative of fluorescence intensity as the system response for measuring sample antigen concentration in T sensor based competitive diffusion immunoassay leads to lower uncertainty and higher detection sensitivity. PMID- 26858818 TI - Human induced pluripotent stem cells derived endothelial cells mimicking vascular inflammatory response under flow. AB - Endothelial cells (ECs) have great potential in vascular diseases research and regenerative medicine. Autologous human ECs are difficult to acquire in sufficient numbers in vitro, and human induced pluripotent stem cells (iPSCs) offer unique opportunity to generate ECs for these purposes. In this work, we present a new and efficient method to simply differentiate human iPSCs into functional ECs, which can respond to physiological level of flow and inflammatory stimulation on a fabricated microdevice. The endothelial-like cells were differentiated from human iPSCs within only one week, according to the inducing development principle. The expression of endothelial progenitor and endothelial marker genes (GATA2, RUNX1, CD34, and CD31) increased on the second and fourth days after the initial inducing process. The differentiated ECs exhibited strong expression of cells-specific markers (CD31 and von Willebrand factor antibody), similar to that present in human umbilical vein endothelial cells. In addition, the hiPSC derived ECs were able to form tubular structure and respond to vascular like flow generated on a microdevice. Furthermore, the human induced pluripotent stem cell-endothelial cells (hiPSC-ECs) pretreated with tumor necrosis factor (TNF-alpha) were susceptible to adhesion to human monocyte line U937 under flow condition, indicating the feasibility of this hiPSCs derived microsystem for mimicking the inflammatory response of endothelial cells under physiological and pathological process. PMID- 26858819 TI - A scalable label-free approach to separate human pluripotent cells from differentiated derivatives. AB - The broad capacity of pluripotent human embryonic stem cells (hESC) to grow and differentiate demands the development of rapid, scalable, and label-free methods to separate living cell populations for clinical and industrial applications. Here, we identify differences in cell stiffness, expressed as cell elastic modulus (CEM), for hESC versus mesenchymal progenitors, osteoblast-like derivatives, and fibroblasts using atomic force microscopy and data processing algorithms to characterize the stiffness of cell populations. Undifferentiated hESC exhibited a range of CEMs whose median was nearly three-fold lower than those of differentiated cells, information we exploited to develop a label-free separation device based on the principles of tangential flow filtration. To test the device's utility, we segregated hESC mixed with fibroblasts and hESC mesenchymal progenitors induced to undergo osteogenic differentiation. The device permitted a throughput of 10(6)-10(7) cells per min and up to 50% removal of specific cell types per single pass. The level of enrichment and depletion of soft, pluripotent hESC in the respective channels was found to rise with increasing stiffness of the differentiating cells, suggesting CEM can serve as a major discriminator. Our results demonstrate the principle of a scalable, label free, solution for separation of heterogeneous cell populations deriving from human pluripotent stem cells. PMID- 26858820 TI - Low-frequency dielectrophoretic response of a single particle in aqueous suspensions. AB - We use optical tweezers-based dielectrophoresis (DEP) force spectroscopy to investigate the roles of the electrical double layer in the AC dielectric response of an individual colloidal particle in an aqueous medium. Specifically, we measure the DEP crossover frequency as a function of particles size, medium viscosity, and temperature. Experimental results were compared to low frequency relaxation mechanisms predicted by Schwarz, demonstrating the dielectrophoretic responses in the frequency range between 10 kHz and 1 MHz were dominated by counterion diffusion within the electric double layer. PMID- 26858821 TI - Enhanced contactless dielectrophoresis enrichment and isolation platform via cell scale microstructures. AB - We designed a new microfluidic device that uses pillars on the same order as the diameter of a cell (20 MUm) to isolate and enrich rare cell samples from background. These cell-scale microstructures improve viability, trapping efficiency, and throughput while reducing pearl chaining. The area where cells trap on each pillar is small, such that only one or two cells trap while fluid flow carries away excess cells. We employed contactless dielectrophoresis in which a thin PDMS membrane separates the cell suspension from the electrodes, improving cell viability for off-chip collection and analysis. We compared viability and trapping efficiency of a highly aggressive Mouse Ovarian Surface Epithelial (MOSE) cell line in this 20 MUm pillar device to measurements in an earlier device with the same layout but pillars of 100 MUm diameter. We found that MOSE cells in the new device with 20 MUm pillars had higher viability at 350 VRMS, 30 kHz, and 1.2 ml/h (control 77%, untrapped 71%, trapped 81%) than in the previous generation device (untrapped 47%, trapped 42%). The new device can trap up to 6 times more cells under the same conditions. Our new device can sort cells with a high flow rate of 2.2 ml/h and throughput of a few million cells per hour while maintaining a viable population of cells for off-chip analysis. By using the device to separate subpopulations of tumor cells while maintaining their viability at large sample sizes, this technology can be used in developing personalized treatments that target the most aggressive cancerous cells. PMID- 26858823 TI - Dielectric model for Chinese hamster ovary cells obtained by dielectrophoresis cytometry. AB - We present a dielectric model and its parameters for Chinese hamster ovary (CHO) cells based on a double-shell structure which includes the cell membrane, cytoplasm, nuclear envelope, and nucleoplasm. Employing a dielectrophoresis (DEP) based technique and a microfluidic system, the DEP response of many single CHO cells is measured and the spectrum of the Clausius-Mossotti factor is obtained. The dielectric parameters of the model are then extracted by curve-fitting to the measured spectral data. Using this approach over the 0.6-10 MHz frequency range, we report the values for CHO cells' membrane permittivity, membrane thickness, cytoplasm conductivity, nuclear envelope permittivity, and nucleoplasm conductivity. The size of the cell and its nuclei are obtained using optical techniques. PMID- 26858822 TI - Two-dimensional arrays of cell-laden polymer hydrogel modules. AB - Microscale technologies offer the capability to generate in vitro artificial cellular microenvironments that recapitulate the spatial, biochemical, and biophysical characteristics of the native extracellular matrices and enable systematic, quantitative, and high-throughput studies of cell fate in their respective environments. We developed a microfluidic platform for the generation of two-dimensional arrays of micrometer-size cell-laden hydrogel modules (HMs) for cell encapsulation and culture. Fibroblast cells (NIH 3T3) and non-adherent T cells (EL4) encapsulated in HMs showed high viability and proliferation. The platform was used for real-time studies of the effect of spatial constraints and structural and mechanical properties of HMs on cell growth, both on the level of individual cells. Due to the large number of cell-laden HMs and stochastic cell distribution, cell studies were conducted in a time- and labor efficient manner. The platform has a broad range of applications in the exploration of the role of chemical and biophysical cues on individual cells, studies of in vitro cell migration, and the examination of cell-extracellular matrix and cell-cell interactions. PMID- 26858824 TI - Positive Modulation of Pink Nelumbo nucifera Flowers on Memory Impairment, Brain Damage, and Biochemical Profiles in Restraint Rats. AB - Due to the crucial role of oxidative stress in the stress-induced memory deficit, the benefit of substance possessing antioxidant effect is focused. Since no data are available, we aimed to determine the effect of Nelumbo nucifera flowers extract on spatial memory and hippocampal damage in stressed rats. Male Wistar rats, weighing 250-350 g, were orally given N. nucifera extract at doses of 10, 10, and 200 mg.kg(-1) 45 minutes before the exposure to 12-hour restraint stress. The spatial memory and serum corticosterone were assessed at 7 and 14 days of study period. At the end of study, acetylcholinesterase (AChE), monoamine oxidase type A and monoamine oxidase type B (MAO-A and MAO-B), oxidative stress status, neuron density, and Ki67 expression in hippocampus were also assessed. The results showed that N. nucifera extract decreased memory deficit and brain damage, serum corticosterone, oxidative stress status, AChE, and MAO-A and MAO-B activities but increased neuron density and Ki67 expression in hippocampus. These suggested that the improved oxidative stress status, adult neurogenesis, and cholinergic and monoaminergic functions might be responsible for the protective effect against stress-related brain damage and dysfunction of the extract. Therefore, N. nucifera extract is the potential neuroprotective and memory enhancing agent. However, further researches are still required. PMID- 26858825 TI - Discriminating Bipolar Disorder From Major Depression Based on SVM-FoBa: Efficient Feature Selection With Multimodal Brain Imaging Data. AB - Discriminating between bipolar disorder (BD) and major depressive disorder (MDD) is a major clinical challenge due to the absence of known biomarkers; hence a better understanding of their pathophysiology and brain alterations is urgently needed. Given the complexity, feature selection is especially important in neuroimaging applications, however, feature dimension and model understanding present serious challenges. In this study, a novel feature selection approach based on linear support vector machine with a forward-backward search strategy (SVM-FoBa) was developed and applied to structural and resting-state functional magnetic resonance imaging data collected from 21 BD, 25 MDD and 23 healthy controls. Discriminative features were drawn from both data modalities, with which the classification of BD and MDD achieved an accuracy of 92.1% (1,000 bootstrap resamples). Weight analysis of the selected features further revealed that the inferior frontal gyrus may characterize a central role in BD-MDD differentiation, in addition to the default mode network and the cerebellum. A modality-wise comparison also suggested that functional information outweighs anatomical by a large margin when classifying the two clinical disorders. This work validated the advantages of multimodal joint analysis and the effectiveness of SVM-FoBa, which has potential for use in identifying possible biomarkers for several mental disorders. PMID- 26834972 TI - Case Report: Atypical Cornelia de Lange Syndrome. AB - Cornelia de Lange Syndrome (CdLS) (also called Bushy Syndrome or Amsterdam dwarfism), is a genetic disorder that can lead to several alterations. This disease affects both physical and neuropsychiatric development. The various abnormalities include facial dysmorphia (arched eyebrows, synophrys, depressed nasal bridge, long philtrum, down-turned angles of the mouth), upper-extremity malformations, hirsutism, cardiac defects, and gastrointestinal alterations. The prevalence of this syndrome is approximately one per 15,000. Ultrasound is not the perfect means to diagnose CdLS, however, many abnormalities can be detected prenatally by scrupulous image observation. We report an atypical CdLS case characterized by increased nuchal translucency in the first trimester, normal karyotype, saddle nose, micrognathia with receding jaw, low set ears, facies senilis, arthrogryposis of the hands, absence of the Aranzio ductus venous, dilatation of gallbladder and bowel, a unique umbilical artery, increased volume of amniotic fluid, and intrauterine growth retardation ending with the interruption of pregnancy. PMID- 26834975 TI - Dynamics of Ebola epidemics in West Africa 2014. AB - This paper investigates the dynamics of Ebola virus transmission in West Africa during 2014. The reproduction numbers for the total period of epidemic and for different consequent time intervals are estimated based on a simple linear model. It contains one major parameter - the average infectious period that defines the dynamics of epidemics. Numerical implementations are carried out on data collected from three countries Guinea, Sierra Leone and Liberia as well as the total data collected worldwide. Predictions are provided by considering different scenarios involving the average times of infectiousness for the next few months and the end of the current epidemic is estimated according to each scenario. PMID- 26858826 TI - Hybrid Tissue Engineering Scaffolds by Combination of Three-Dimensional Printing and Cell Photoencapsulation. AB - Three-dimensional (3D) printing offers versatile possibilities for adapting the structural parameters of tissue engineering scaffolds. However, it is also essential to develop procedures allowing efficient cell seeding independent of scaffold geometry and pore size. The aim of this study was to establish a method for seeding the scaffolds using photopolymerizable cell-laden hydrogels. The latter facilitates convenient preparation, and handling of cell suspension, while distributing the hydrogel precursor throughout the pores, before it is cross linked with light. In addition, encapsulation of living cells within hydrogels can produce constructs with high initial cell loading and intimate cell-matrix contact, similar to that of the natural extra-cellular matrix (ECM). Three dimensional scaffolds were produced from poly(lactic) acid (PLA) by means of fused deposition modeling. A solution of methacrylamide-modified gelatin (Gel MOD) in cell culture medium containing photoinitiator Li-TPO-L was used as a hydrogel precursor. Being an enzymatically degradable derivative of natural collagen, gelatin-based matrices are biomimetic and potentially support the process of cell-induced remodeling. Preosteoblast cells MC3T3-E1 at a density of 10 * 106 cells per 1 mL were used for testing the seeding procedure and cell proliferation studies. Obtained results indicate that produced constructs support cell survival and proliferation over extended duration of our experiment. The established two-step approach for scaffold seeding with the cells is simple, rapid, and is shown to be highly reproducible. Furthermore, it enables precise control of the initial cell density, while yielding their uniform distribution throughout the scaffold. Such hybrid tissue engineering constructs merge the advantages of rigid 3D printed constructs with the soft hydrogel matrix, potentially mimicking the process of ECM remodeling. PMID- 26858829 TI - Disinfectant-susceptibility of multi-drug-resistant Mycobacterium tuberculosis isolated in Japan. AB - BACKGROUND: Multi-drug-resistant Mycobacterium tuberculosis has been an important problem in public health around the world. However, limited information about disinfectant-susceptibility of multi-drug-resistant strain of M. tuberculosis was available. FINDINGS: We studied susceptibility of several Japanese isolates of multi-drug-resistant M. tuberculosis against disinfectants, which are commonly used in clinical and research laboratories. We selected a laboratory reference strain (H37Rv) and eight Japanese isolates, containing five drug-susceptible strains and three multi-drug-resistant strains, and determined profiles of susceptibility against eight disinfectants. The M. tuberculosis strains were distinguished into two groups by the susceptibility profile. There was no relationship between multi-drug-resistance and disinfectant-susceptibility in the M. tuberculosis strains. Cresol soap and oxydol were effective against all strains we tested, regardless of drug resistance. CONCLUSIONS: Disinfectant resistance is independent from multi-drug-resistance in M. tuberculosis. Cresol soap and oxydol were effective against all strains we tested, regardless of drug resistance. PMID- 26858830 TI - Expression of the PlA2 allele of glycoprotein IIIa and its impact on platelet function. AB - BACKGROUND: The platelet fibrinogen receptor represents the final common pathway of platelet activation, and is formed from two glycoprotein (GP) subunits (GPIIb/IIIa). Carriage of the mutant PlA2 allele of GPIIIa has been shown to confer an increased risk of cardiovascular events, but published studies have disagreed as to the mechanism for this association. OBJECTIVES: To assess whether carriage of the PlA2 allele conforms to Mendelian patterns of expression and to identify whether carriage of the mutant allele modulates platelet function. METHODS: Expression of the PlA2 allele was assessed in both healthy subjects (n = 25) and patients with known coronary artery disease (n = 90) through the development and validation of a liquid chromatography, tandem mass spectrometry (LC-MS/MS) assay. Platelet function was assessed in the patient cohort in response to multiple agonists, and these data were analysed in the context of the proteomic data. RESULTS: Expression of the wild-type PlA1 allele and mutant PlA2 alleles was readily quantifiable and conformed to Mendelian patterns in both healthy and patient cohorts. Patients who were homozygous for the mutant PlA2 allele had an increased aggregatory response to adenosine diphosphate, collagen, adrenaline, ristocetin, thrombin receptor-activating peptide 6 and U46619, when assessed using agonist-concentration response curves. CONCLUSIONS: These findings support the hypothesis that carriage of the mutant PlA2 allele mediates an increased risk of cardiovascular events through the modulation of platelet reactivity. PMID- 26858831 TI - Total thyroidectomy: Conventional Suture Ligation technique versus sutureless techniques using Harmonic Scalpel or Maxium. AB - OBJECTIVES: Harmonic Scalpel (HS) and Maxium (MAX) are surgical shears that enable simultaneous vessel sealing and tissue coagulation. This study compares the outcome of Total Thyroidectomy (TT) using Conventional Suture Ligation (CSL) technique versus (vs) two sutureless techniques; H S and MAX techniques in terms of safety, operative time, blood drainage volume, hospital stay and surgical complications. STUDY DESIGN: This is a prospective observational cohort study. SETTING: This study was performed in AL-Karama Teaching Hospital/College of Medicine/University of Wasit/Iraq. PATIENTS AND METHODS: This study was performed from June 2012 to 2015. A total of 80 patients, 60 patients were females and 20 patients were males (average/mean of age was 39/38 years). They underwent TT after been randomized into the following three groups: CSL group when Suture Ligation Technique was used, HS group when Harmonic Scalpel was used and MAX group when bipolar electrosurgery Maxium was used. RESULTS: The postoperative evaluation of operative time, blood drainage volume and surgical complications revealed no statistically significant differences between HS group & MAX group, but there were statistically significant differences between CSL group vs. HS and MAX groups. Operative time statistics showed significant differences between CSL vs. HS and MAX groups, 113 +/- 10.9 minutes (min), 93 +/- 13 min and 92 +/- 10.6 min respectively, p-value < 0.001 and 95% confidence interval [CI] (92.3712, 101.6288). The postoperative blood drainage volumes were significantly different between the three groups: CSL group = 150 +/- 12.7 ml, HS group = 89 +/- 16.21 ml and MAX group = 118 +/- 9.6 ml, P-value = 0.046 and 95% [CI] (89.9932, 99.6068). CONCLUSIONS: HS and MAX are safe, effective, and time-saving techniques. They are also associated with low blood loss and low complication rates. HS and MAX are good alternative techniques to CSL for thyroid surgery. PMID- 26858832 TI - A rare presentation of multiple endocrine neoplasia (MEN) type 2A syndrome. AB - Peptic ulcer disease may be a manifestation of symptomatic primary hyperparathyroidism. A case of an intractable complicated peptic ulcer disease secondary to hypercalcaemia from multiple endocrine neoplasia type 2A is presented. Hypercalcaemia should always be excluded as a cause of recurrent, or complicated peptic ulcer disease. PMID- 26858833 TI - Are we following an algorithm for managing chronic anal fissure? A completed audit cycle. AB - BACKGROUND: Anal fissure is one of the commonest proctological diseases with considerable national variation in sequential treatment. We aimed to audit our compliance of chronic anal fissure (CAF) management with national guidance provided by the Association of Coloproctology of Great Britain and Ireland (ACPGBI). METHODS: We retrospectively audited patients presenting to outpatient clinics with CAF over a 6-month period. Using electronic patient records, notes and clinic letters, we compared their management with ACPGBI algorithm. A prospective re-audit was then performed. RESULTS: Forty-one patients were included in the analysis (59% male). Sixty-eight percent (n = 28/41) of patients were appropriately started on conservative dietary therapy, of whom only 7.1% (n = 2/28) had treatment success. Eighty-nine percent (n = 25/28) were then appropriately treated with either topical diltiazem 2% or GTN 0.4%. Overall, 43.9% (n = 18/41) of all patients' entire management strategy adhered to the ACPGBI guidelines. In total, 48.8% (n = 20/41) patients had surgical treatment (excluding Botox), of which only 15% (n = 3/20) had undergone ACPGBI-compliant management. After local dissemination of results and education, the re-audit of 20 patients showed significant improvement in adherence to the guidelines (43.9% vs. 95%; P = 0.0001). CONCLUSIONS: Topical creams were the most successful treatments (50%; n = 9/18) in ACPGBI-compliant strategies. Importantly, these data suggests that compliance with the ACPGBI algorithm leads to healing without surgery in 83.3% (n = 15/18) of patients, compared to 26.1% (n = 6/23) with non compliant methods (P = 0.0004). This highlights the benefit of early conservative and medical management of CAF, before attempting surgery. PMID- 26858834 TI - A quality improvement project using a problem based post take ward round proforma based on the SOAP acronym to improve documentation in acute surgical receiving. AB - OBJECTIVES: Ward round documentation provides one of the most important means of communication between healthcare professionals. We aimed to establish if the use of a problem based standardised proforma can improve documentation in acute surgical receiving. METHODS: Gold standards were established using the RCSE record keeping guidelines. We audited documentation for seven days using the following headings: patient name/identification number, subjective findings, objective findings, clinical impression/diagnosis, plan, diet status, discharge decision, discharge planning, signature, and grade. After the initial audit cycle, a ward round proforma was introduced using the above headings and re audited over a seven day period. RESULTS: The pre-intervention arm contained 50 patients and the post intervention arm contained 47. The following headings showed an improvement in documentation compliance to 100%: patient name/identification number vs 96%, subjective findings vs 84%, objective findings vs 48%, plan vs 98%, signature vs 96%, and grade vs 62%. Documentation of the clinical impression/diagnosis improved to 98% vs 30%, diet status rose to 83% vs 16%, discharge decision to 66% vs 16%, and discharge planning to 40% vs 20%. CONCLUSIONS: Standardised proformas improve the documentation of post-take ward round notes. This helps to clarify the onward management plan for all aspects of a patient's care and will help avoid adverse events and litigation. This should improve the quality and safety of Patient Care. PMID- 26858835 TI - Individual and community-level factors associated with introduction of prelacteal feeding in Ethiopia. AB - BACKGROUND: Ethiopia is a country with low optimal breast feeding practice, and prelacteal feeding is still a norm. Introduction of prelacteal feeding is a known barrier for optimal breast feeding practices. However, knowledge on determinants of introduction of prelacteal feeding is minimal. This study aimed to identify the effects of individual and community-level factors in the introduction of prelacteal feeding in Ethiopia. METHODS: Data for this study was extracted from the nationally representative 2011 Ethiopia Demographic and Health Survey (EDHS) and focused on a sample from child data, with a sample from 576 clusters of 7692 children who were last-born in the past five years preceding the survey. The data was collected using two-stage cluster design, in which enumeration areas forming the first stage and households making the second stage. A two-level mixed effect multivariable logistic regression model was fitted to determine the individual and community-level factors associated with introduction of prelacteal feeding. RESULTS: From the total sample of children 28.92 % were fed prelacteals. Butter (n = 1143), plain water (n = 395) and milk-other than breast milk (n = 323) were commonly used prelacteals. In multivariable two-level mixed effect model; caesarean mode of delivery (Adjusted odds ratio (AOR) = 1.87; 95 % CI 1.28, 2.73), and late initiation of breastfeeding (AOR = 5.32; 95 % CI 4.65, 6.09) were both positively associated with the odds of giving prelacteals. Higher economic status 28 % (AOR = 0.72; 95 % CI 0.54, 0.98), giving birth at hand of non-health personnel birth assistance (AOR = 0.68; 95 % CI 0.54, 0.87), large birth size of child (AOR = 0.80; 95 % CI 0.68, 0.95) and high community antenatal care use (AOR = 0.58; 95 % CI 0.38, 0.87) were negatively associated with the odds of giving prelacteals. Significant variation in prelacteal feeding practice was also seen among ethnic and religious groups, and across regions. CONCLUSIONS: The prevalence of prelacteal feeding was high that remained a challenge for optimal breastfeeding in Ethiopia. Not only individual-level factors, but also community level factors contribute to prelacteal feeding practice. Increasing access to health education through increasing maternal health care service coverage and community involvement is crucial. PMID- 26858836 TI - Validity of self-reported out-of-school physical activity among Finnish 11-year old children. AB - BACKGROUND: The aim of this study is to assess the repeatability and validity of the Finnish 11-year old children's out-of-school physical activity (PA) questionnaire using accelerometer as reference method. A sub-sample of children (N = 155, 60 % participant rate) participating in the Finnish Health in Teens study was recruited in 2013. Children completed a questionnaire measuring PA two times, and wore an accelerometer for seven days. The questions and accelerometer data were transformed into average minutes of behaviors per day. Repeatability was measured by intra-class correlations. To test validity, Spearman correlations between the questions and accelerometer was checked and the Bland-Altman model was conducted. Kruskall-Wallis tests were conducted to examine the ranking capability of questionnaire. RESULTS: The intra-class correlations between two measurement times of questionnaire had substantial agreement. The Spearman correlations between the questions and accelerometer were poor. Based on Kruskal Wallis tests, the questionnaire was moderately able to rank children according to their levels of PA. CONCLUSIONS: The repeatability of the questionnaire had substantial agreement among 11-years-old, whereas it moderately classifies objectively measured PA. If the aim is to measure children's duration of PA, the accelerometer might be a better measurement method to use among 11-year old children. If the aim is to classify children according to their behavior, then the used questionnaire is moderately appropriate. PMID- 26858837 TI - Fluconazole in the treatment of Cushing's disease. AB - Ketoconazole was a first-line agent for suppressing steroidogenesis in Cushing's disease. It now has limited availability. Fluconazole, another azole antifungal, is an alternative, although its in vivo efficacy is unclear. A 61-year-old female presented with weight gain, abdominal striae and worsening depression. HbA1c increased to 76 mmol/mol despite increasing insulin. Investigations confirmed cortisol excess; afternoon serum cortisol was 552 nmol/l with an inappropriate ACTH of 9.3 pmol/l. In total, 24-h urinary free cortisol (UFC):creatinine ratio was 150 nmol/mmol with failure to suppress after 48 h of low-dose dexamethasone. Pituitary MRI revealed a 4-mm microadenoma. Inferior petrosal sinus sampling confirmed Cushing's disease. Transsphenoidal resection was performed and symptoms improved. However, disease recurred 6 months later with elevated 24-h UFC >2200 nmol/day. Metyrapone was commenced at 750 mg tds. Ketoconazole was later added at 400 mg daily, with dose reduction in metyrapone. When ketoconazole became unavailable, fluconazole 200 mg daily was substituted. Urine cortisol:creatinine ratio rose, and the dose was increased to 400 mg daily with normalisation of urine hormone levels. Serum cortisol and urine cortisol:creatinine ratios remain normal on this regimen at 6 months. In conclusion, to our knowledge, this is the first case demonstrating prolonged in vivo efficacy of fluconazole in combination with low-dose metyrapone for the treatment of Cushing's disease. Fluconazole has a more favourable toxicity profile, and we suggest that it is a potential alternative for medical management of Cushing's disease. LEARNING POINTS: Surgery remains first line for the management of Cushing's disease with pharmacotherapy used where surgery is unsuccessful or there is persistence of cortisol excess.Ketoconazole has previously been used to treat cortisol excess through inhibition of CYP450 enzymes 11-beta-hydroxylase and 17-alpha-hydroxylase, though its availability is limited in many countries.Fluconazole shares similar properties to ketoconazole, although it has less associated toxicity.Fluconazole represents a suitable alternative for the medical management of Cushing's disease and proved an effective addition to metyrapone in the management of this case. PMID- 26858838 TI - First report of Oxa-72-producing Acinetobacter calcoaceticus in Lebanon. AB - Emergence of carbapenem-resistant Acinetobacter spp. has been increasingly reported worldwide. We report here the first detection of an Acinetobacter calcoaceticus isolate from vegetables in Lebanon carrying the bla Oxa-72 gene. These findings show that the Lebanese environment may constitute a potential reservoir for this antibiotic resistance gene. PMID- 26858839 TI - Serum fatty acids, biochemical indices and antioxidant status in goats fed canola oil and palm oil blend. AB - BACKGROUND: Dietary supplementation of unsaturated fats in ruminants, if not stabilized, can instigate oxidative stress which can have negative impact on production performance and enhance the susceptibility to various diseases. The current study examined the effect of dietary 80 % canola oil and 20 % palm oil blend (CPOB) on serum fatty acids, antioxidant profile and biochemical indices in goats. Thirty Boer bucks (4-5 months old; initial BW, 20.34 +/- 0.77 kg) were randomly assigned to diets containing 0, 4 or 8 % CPOB and fed daily for a period of 90 days. Blood was sampled from the goats on 0, 30, 60 and 90 days of the trial and the serum was analyzed for fatty acids, cholesterol, glucose, total protein, antioxidants and lipid oxidation. RESULTS: Neither diet nor sampling time influenced serum TBARS value, catalase, glutathione peroxidase and superoxide dismutase activities, LDL cholesterol, VLDL cholesterol, triglycerides, glucose and total protein. Goats fed 4 and 8 % CPOB had higher (P < 0.05) total cholesterol and HDL cholesterol than the control goats on day 30, 60 and 90. The proportion of C15:0 decreased with increasing level of CPOB on day 30 and 60. Serum C18:1n-9 increased with increasing level of CPOB in diet on day 60. The proportion of C18:3n-3 and C22:5n-3 increased (P < 0.05), while the proportion of C18:2n-6 decreased (P < 0.05) with increase in the level of CPOB on day 60 and 90. Dietary CPOB did not affect serum total carotenoid and delta tocopherol but did increase (P < 0.05) alpha and gamma-tocopherol. CONCLUSION: Dietary canola oil and palm oil blend could be supplemented in diets without instigating oxidative stress in goats. PMID- 26858841 TI - Comment on "The Success of Cataract Surgery and the Preoperative Measurement of Retinal Function by Electrophysiological Techniques". PMID- 26858840 TI - Reduction of Parathyroid Hormone with Vitamin D Supplementation in Blacks: A Randomized Controlled Trial. AB - BACKGROUND: Response of parathyroid hormone (PTH) to vitamin D supplementation is determined by the baseline PTH level and change in vitamin D status. Conflicting reports in Blacks exist on the PTH response to vitamin D to supplementation. METHODS: During 3 winters from 2007-2010, 328 healthy Blacks (median age, 51 years) living in Boston, MA were randomized into a 4-arm, double-blind trial for 3 months of placebo, 1000, 2000, or 4000 IU of vitamin D3. PTH was measured in 254 participants at baseline and at the end of vitamin D supplementation period. RESULTS: The differences in PTH between baseline and 3 months were 3.93 pg/mL for those receiving placebo, -3.37 pg/mL for those receiving 1000 IU/d, -6.76 pg/mL for those receiving 2000 IU/d, and -8.99 pg/mL for those receiving 4000 IU/d ( 2.98 pg/mL for each additional 1000 IU/d of vitamin D3; p<0.001). CONCLUSION: We found a significant decrease in PTH with increasing doses of vitamin D supplementation up to intakes of 4000 IU/d in Blacks. Clinical Trials.gov: NCT00585637. PMID- 26858842 TI - Evaluation of Intrastromal Riboflavin Concentration in Human Corneas after Three Corneal Cross-Linking Imbibition Procedures: A Pilot Study. AB - Purpose. To compare stromal riboflavin concentration after three corneal cross linking (CXL) imbibition procedures: standard (EpiOff), transepithelial corneal (EpiOn), and iontophoresis-assisted technique (Ionto) using 0.1% hypotonic riboflavin phosphate. Methods. Randomized open-label pilot clinical study. Twelve corneas/12 patients with advanced keratoconus were randomly divided into 4 groups for CXL (n = 3). The corneas underwent imbibition with standard riboflavin EpiOff and with enhanced riboflavin solution (RICROLIN+) EpiOff, EpiOn, and iontophoresis techniques. Thereafter, deep anterior lamellar keratectomy procedure was performed and the obtained debrided corneal tissues were frozen. The maximal intrastromal riboflavin concentration was measured by high performance liquid chromatography/mass spectrometry (mcg/dg). Results. The mean stromal concentration of riboflavin was 2.02 +/- 0.72 mcg/dg in EpiOff group, 4.33 +/- 0.12 mcg/g in EpiOff-RICROLIN+ group, 0.63 +/- 0.21 mcg/dg in EpiOn RICROLIN+ group, and 1.15 +/- 0.27 mcg/dg in iontophoresis RICROLIN+ group. A 7 fold decrease in intrastromal riboflavin concentration was observed comparing EpiOn-RICROLIN+ and EpiOff-RICROLIN+ groups. Conclusion. The present pilot study indicates that both transepithelial CXL techniques in combination with hypotonic enhanced riboflavin formulation (RICROLIN+) were still inferior to the standard CXL technique; however, larger clinical studies to further validate the results are needed and in progress. PMID- 26858843 TI - Nose and Midface Augmentation by Rib Cartilage Grafts: Methods and Outcome in 32 Cases. AB - Recession of the midface is a relatively common condition that can have a negative impact on facial and nasal aesthetic appearance, and it poses a challenge to plastic surgeons. In cases with generalized maxillary retrusion and/or malocclusion, bone advancement surgery is required, but in localized cases, mostly seen in cleft lip patients, the quest is for an ideal material and a proper technique that would be used to augment the receding area. Throughout a period of seven years, thirty-two patients with nose and midface retrusion were managed by a construct of rib cartilage grafts designed to compensate the deficiency at the maxillary, piriform, and premaxillary areas. Results were satisfactory for most patients in terms of improved fullness of malar area, improved nasal tip projection and rotation, and improvement of upper lip. The presented technique of rib cartilage grafting is a safe and effective method for nose and midface augmentation. PMID- 26858844 TI - Seasonal Temperature Changes Do Not Affect Cardiac Glucose Metabolism. AB - FDG-PET/CT is widely used to diagnose cardiac inflammation such as cardiac sarcoidosis. Physiological myocardial FDG uptake often creates a problem when assessing the possible pathological glucose metabolism of the heart. Several factors, such as fasting, blood glucose, and hormone levels, influence normal myocardial glucose metabolism. The effect of outdoor temperature on myocardial FDG uptake has not been reported before. We retrospectively reviewed 29 cancer patients who underwent PET scans in warm summer months and again in cold winter months. We obtained myocardial, liver, and mediastinal standardized uptake values (SUVs) as well as quantitative cardiac heterogeneity and the myocardial FDG uptake pattern. We also compared age and body mass index to other variables. The mean myocardial FDG uptake showed no significant difference between summer and winter months. Average outdoor temperature did not correlate significantly with myocardial SUVmax in either summer or winter. The heterogeneity of myocardial FDG uptake did not differ significantly between seasons. Outdoor temperature seems to have no significant effect on myocardial FDG uptake or heterogeneity. Therefore, warming the patients prior to attending cardiac PET studies in order to reduce physiological myocardial FDG uptake seems to be unnecessary. PMID- 26858846 TI - Ultrasound Findings in Hand Joints Involvement in Patients with Psoriatic Arthritis and Its Correlation with Clinical DAS28 Score. AB - Objective. To determine the frequency of the various ultrasound findings in hand joints in patients with psoriatic arthritis and correlate grayscale and Power Doppler ultrasonography findings with Disease Activity Score 28. Methods. This prospective study was performed in 30 patients. Ultrasound evaluation of 28 joints of both hands was undertaken and various findings were recorded including synovial hypertrophy, Power Doppler abnormality, soft tissue thickening, tendonitis, joint effusion, periosteal reaction, and erosions. Composite ultrasound scores and Disease Activity Score 28 were calculated and compared. Spearman correlation was used to see relationship between the ultrasound and DAS28 scores. Results. Ultrasound detected more abnormalities in the hand joints than did clinical examination. The frequency of various ultrasound abnormalities was as follows: Synovial hypertrophy was seen in 100%, Power Doppler abnormality suggesting hypervascularity was seen in 36.7%, soft tissue thickening was seen in 66.7%, periosteal reaction was seen in 33.3%, erosions were seen in 30% (mostly in DIP and PIP joints), and flexor tendonitis was seen in 6.7% of patients. Significant correlation was found between Disease Activity Score 28 and grayscale joint score (GSJS) (Spearman's rho: 0.499; P: 0.005), grayscale joint count (GSJC) (rho: 0.398; P: 0.029), and Power Doppler joint score (PDJS) (rho: 0.367; P: 0.046). There was a statistically significant difference between remission and low disease activity group and moderate disease activity group in terms of GSJC, GSJS, PDJC, and PDJS (P < 0.05). These ultrasound measures were higher in moderate disease activity zone patients. Conclusion. Ultrasound is a useful modality for the objective assessment of psoriatic arthritis. Ultrasound including Power Doppler can be used as a modality for assessment of severity of psoriatic arthritis as it correlates with the clinical scoring. PMID- 26858847 TI - Acute Unilateral Blindness from Superior Ophthalmic Vein Thrombosis: A Rare Presentation of Nephrotic Syndrome from Class IV Lupus Nephritis in the Absence of Antiphospholipid or Anticardiolipin Syndrome. AB - Patients with systemic lupus erythematosus (SLE) are at high risk of arterial and venous thrombosis secondary to anti-phospholipid antibodies. Herein, we are presenting an interesting case of venous thrombosis in a patient with SLE in the absence of anti-phospholipid antibodies. PMID- 26858845 TI - Congenital Extrahepatic Portosystemic Shunts: Spectrum of Findings on Ultrasound, Computed Tomography, and Magnetic Resonance Imaging. AB - Congenital extrahepatic portosystemic shunt (CEPS) is a rare disorder characterised by partial or complete diversion of portomesenteric blood into systemic veins via congenital shunts. Type I is characterised by complete lack of intrahepatic portal venous blood flow due to an end to side fistula between main portal vein and the inferior vena cava. Type II on the other hand is characterised by partial preservation of portal blood supply to liver and side to side fistula between main portal vein or its branches and mesenteric, splenic, gastric, and systemic veins. The presentation of these patients is variable. Focal liver lesions, most commonly nodular regenerative hyperplasia, are an important clue to the underlying condition. This pictorial essay covers imaging characteristics in abdominopelvic region. PMID- 26858848 TI - A Case Report on Oral Subcutaneous Dirofilariasis. AB - Dirofilariasis is an uncommon zoonotic parasitic infection affecting human. The natural hosts for this nematode are animals such as dogs, cats, foxes, jackals, and raccoons. This disease is endemic in South Eastern United States, Australia, Europe, and Central and Southern Asia. Dirofilaria immitis and D. repens are the common mosquito borne filarial nematodes that cause infection. Several species of mosquitos including Mansonia uniformis, M. annulifera, and Aedes aegypti are the potential vectors for this disease in Sri Lanka. Two rare cases of dirofilariasis presenting as facial and intraoral lumps are presented. PMID- 26858849 TI - Etiology of Ascites and Pleural Effusion Associated with Ovarian Tumors: Literature Review and Case Reports of Three Ovarian Tumors Presenting with Massive Ascites, but without Peritoneal Dissemination. AB - Borderline ovarian tumors are benign but relatively large tumors that are often initially mistaken as ovarian cancers. We report three cases of stage I borderline ovarian tumors having massive ascites that we (preoperatively) suspected of being advanced ovarian cancer. The three patients (35, 47, and 73 years old) reported feeling fullness of the abdomen before consulting their gynecologist. By CT scan, they were diagnosed with a pelvic tumor accompanied by massive ascites, the diameters of which were 11, 20, and 11 cm, respectively. Postsurgical pathology showed all were stage I borderline ovarian tumors without dissemination; two were mucinous and one was serous. The amount of ascites was 6,300, 2,600, and 3,600 mL, respectively, and was serous in all. Cytodiagnosis of the ascites found that one was positive for tumor cells and two were negative. After resection of the mass, the ascites disappeared in all three cases. No pleural effusion was present at any time. The literature is reviewed concerning ascites and pleural effusions linked to ovarian tumors, and a supposition is forwarded of why pleural effusion presents sporadically in these cases. PMID- 26858850 TI - Castleman Disease of the Parotid Gland: A Report of a Case. AB - Castleman disease is an extremely rare benign lymphoproliferative disorder of unknown etiology. It affects the lymphatic chain in anybody region, although the commonest site is the mediastinum. The head and neck region is the second most common site; however, the salivary glands are rarely affected. We report a case of a 29-year-old Asian lady who presented with a 2-year history of an enlarging left parotid mass. Histopathology of the excisional biopsy confirmed the diagnosis of Castleman disease. PMID- 26858851 TI - Divorcing Mothers' Use of Protective Strategies: Differences Over Time and by Violence Experience. AB - OBJECTIVE: The current study considered protective strategy use at various points in time for divorcing mothers with a range of marital violence experiences (including no history of violence and different types of violence). METHOD: Divorcing mothers (N = 170) from one Midwestern county participated in two in person interviews that included structured assessments of intimate partner violence (IPV) during the last year of marriage and use of protective strategies at three time points - last year of marriage and at separation (both assessed at Time 1) and since the first interview (at a three month follow-up). RESULTS: Divorcing mothers, regardless of marital violence experience, used an array of private and public protective strategies during the last year of marriage, at separation, and at the three-month follow up interview. In general, mothers who experienced coercive controlling violence reported using more protective strategies than mothers who experienced situational couple violence or no violence. Strategy use peaked at separation with an increase in public strategy use. CONCLUSIONS: All divorcing mothers use a range of active coping strategies over time, yet findings emphasize the importance of making distinctions between types of IPV so that divorcing mothers receive individualized resources and support that best meet their needs and minimize potentials risks and losses as they navigate the divorce process. PMID- 26858852 TI - Comparison of Gingiva, Dental Pulp, and Periodontal Ligament Cells From the Standpoint of Mesenchymal Stem Cell Properties. AB - The specific properties of mesenchymal stem cells (MSCs) in oral tissues still remain unknown though their existence has been previously reported. We collected gingiva, dental pulp, and periodontal ligament tissues from removed teeth and isolated MSCs. These MSCs were compared in terms of their yields per tooth, surface epitopes, and differentiation potentials by patient-matched analysis. For in vivo calcification analysis, rat gingival and dental pulp cells mounted on beta-tricalcium phospateTCP were transplanted into the perivertebral muscle of rats for 6 weeks. Gingival cells and dental pulp cells showed higher yield per tooth than periodontal ligament cells (n=6, p<0.05). Yields of periodontal ligament cells were too low for further analysis. Gingival and dental pulp cells expressed MSC markers such as CD44, CD90, and CD166. Gingival and dental pulp cells obtained phenotypes of chondrocytes and adipocytes in vitro. Approximately 60% of the colonies of gingival cells and 40% of the colonies of dental pulp cells were positively stained with alizarin red in vitro, and both gingival and dental pulp cells were calcified in vivo. We clarified properties of MSCs derived from removed teeth. We could obtain a high yield of MSCs with osteogenic potential from gingiva and dental pulp. These results indicate that gingiva and dental pulp are putative cell sources for hard tissue regeneration. PMID- 26858853 TI - Epiphyseal Chondroprogenitors Provide a Stable Cell Source for Cartilage Cell Therapy. AB - Articular cartilage regeneration poses particularly tough challenges for implementing cell-based therapies. Many cell types have been investigated looking for a balanced combination of responsiveness and stability, yet techniques are still far from defining a gold standard. The work presented focuses on the reliable expansion and characterization of a clinical grade human epiphyseal chondroprogenitor (ECP) cell bank from a single tissue donation. A parental human ECP cell bank was established, which provides the seed material for master and working cell banks. ECPs were investigated at both low and high cumulative population doublings looking at morphology, monolayer expansion kinetics, resistance to cryogenic shock, colony-forming efficiency, and cell surface markers. Three-dimensional micropellet assays were used to determine spontaneous extracellular matrix deposition at varying population doublings and monolayer 2D differentiation studies were undertaken to assess the propensity for commitment into other lineages and their stability. ECPs exhibited remarkable homogeneity in expansion with a steady proliferative potential averaging three population doublings over 8 days. Surface marker analysis revealed no detectable contaminating subpopulations or population enrichment during prolonged culture periods. Despite a slight reduction in Sox9 expression levels at higher population doublings in monolayer, nuclear localization was equivalent both in monolayer and in micropellet format. Equally, ECPs were capable of depositing glycosaminoglycans and producing aggrecan, collagen I, and collagen II in 3D pellets both at low and high population doublings indicating a stable spontaneous chondrogenic potential. Osteogenic induction was differentially restricted in low and high population doublings as observed by Von Kossa staining of calcified matrix, with a notable collagen X, MMP13, and ADAMTS5 downregulation. Rare adipogenic induction was seen as evidenced by cytoplasmic lipid accumulation detectable by Oil Red O staining. These findings highlight the reliability, stability, and responsiveness of ECPs over prolonged culture, making them ideal candidates in defining novel strategies for cartilage regeneration. PMID- 26858854 TI - Adequate Time Window and Environmental Factors Supporting Retinal Graft Cell Survival in rd Mice. AB - Postnatal photoreceptor cells can be integrated into the wild-type adult retina in mice, and retinal transplantation is now one therapeutic option for retinal degenerative diseases when photoreceptor degeneration is the primary cause of the disease. The aim of this study was to specify the optimal time window during the course of retinal degeneration and to modulate the host and/or graft environment for a successful transplantation. We first studied the background features of the mice with phosphodiesterase 6b (PDE6b) gene mutation (rd; C3H/Hej) and found that the infiltration of microglia and glial fibrillary acidic protein (GFAP) expression once increased at the peak of rod death (~2-3 weeks of age) but then reduced for a following period until gliosis began to take place with enhanced GFAP expression (~8 weeks of age). The postnatal retinal cells (p4-p7) were successfully transplanted during this period with neurite extension into the host retina. In later transplantations (6 or 8 weeks of age), graft cells survived better in the presence of chondroitinase ABC (ChABC), which digests chondroitin sulfate proteoglycan (CSPG), an essential component of gliosis. In contrast, in earlier transplantations (4 weeks of age), graft cells survived better in the presence of valproic acid (VPA), a neural differentiating reagent, or glatiramer acetate, an immune modulator. These suggest that, immediately after the outer nuclear layer (ONL) degeneration, an inflammatory reaction may be easily induced but the host neurons may be more able to accept donor cells in the presence of neural differentiating factor. These results will help optimize transplantation conditions when we consider clinical application. PMID- 26858855 TI - The Effect of CXCR4 Overexpression on Mesenchymal Stem Cell Transplantation in Ischemic Stroke. AB - There is no doubt that the therapeutic efficacy of mesenchymal stem cells (MSCs) needs improvement. SDF-1 (chemokine for MSC homing) and its receptor CXCR4 play a critical role in the migration of MSCs in ischemia. We investigated the effects of the therapeutic application of MSCs transfected to overexpress CXCR4 using an adenoviral construct in the rat stroke model. Both flow cytometry and Western blot analysis indicated that the level of CXCR4 expression was low in naive hMSCs but was consistently high in CXCR4-hMSCs. In vivo migration test using the transwell system showed that the degree of migration was increased in CXCR4-hMSCs compared with the naive hMSCs and was completely blocked by treatment with AMD3100, an antagonist of the CXCR4 receptor. Compared with rats that received naive MSCs, behavioral recovery was more pronounced in rats that received CXCR4 hMSCs (p = 0.023). An immunohistochemistry study using human nuclear antibody (NuMA) showed that the migration of hMSCs in the ischemic boundary zone was increased after 3 days of injection of CXCR4-hMSCs compared with after injection of naive hMSCs. In addition, polymerase chain reaction was performed to assess the biodistribution of human-specific DNA outside the brain after intravenous injection of hMSCs. The expression of human-specific DNA was increased in the lungs of rats receiving naive MSCs, whereas the human-specific DNA expression was increased in the brain of rats receiving CXCR4-hMSCs. Our results indicate that MSCs transfected with the CXCR4 gene expression cassette may be useful in the treatment of cerebral infarction and may represent a new strategy to enhance the efficacy of MSC therapy. PMID- 26858857 TI - Behavior of Human Articular Chondrocytes During In Vivo Culture in Closed, Permeable Chambers. AB - The exact contribution of transplanted chondrocytes for cartilage tissue repair prior expansion in monolayer culures remains undetermined. At our laboratory, we have created a new permeable chamber to study the chondrogenesis of dedifferentiated cells implanted ectopically in a closed and controlled environment. The behavior of chondrocytes has been studied in settings frequently used in clinical approaches during transplantation, namely injection of autologous chondrocyte cells in suspension (ACI), cells soaked in collagen membranes (MACI), and cells applied in a polymer gel (fibrin). As controls, we have tested the redifferentiation of chondrocytes in cell aggregates, and we have checked the proper functionality of chambers both in vitro and in vivo. After retrieval, firmed tissue-like shapes were recovered only from chambers containing cells seeded in membranes. Histomorphological, immunohistochemical, and ultrastructural analyses revealed synthesis of fibrous-like tissue, characterized by low-density collagen fibers, low collagen type II, abundant collagen type I, and low amounts of proteoglycans. Additionally, neither the collagen membranes nor the fibrin gel was reabsorbed by cells. In summary, our results show that the newly developed permeable chambers function correctly, allowing proper cell feeding and preventing cell leakage or host cell invasion. Additionally, our results suggest that, under these circumstances, chondrocytes are not able to orchestrate formation of hyaline cartilage and have little capacity to degrade artificial membranes or carrier gels such as fibrin. These are interesting observations that should be considered for understanding what role the transplanted chondrocytes play during restoration of articular cartilage after implantation. PMID- 26858856 TI - Improved Hepatocyte Engraftment After Portal Vein Occlusion in LDL Receptor Deficient WHHL Rabbits and Lentiviral-Mediated Phenotypic Correction In Vitro. AB - Innovative cell-based therapies are considered as alternatives to liver transplantation. Recent progress in lentivirus-mediated hepatocyte transduction has renewed interest in cell therapy for the treatment of inherited liver diseases. However, hepatocyte transplantation is still hampered by inefficient hepatocyte engraftment. We previously showed that partial portal vein embolization (PVE) improved hepatocyte engraftment in a nonhuman primate model. We developed here an ex vivo approach based on PVE and lentiviral-mediated transduction of hepatocytes from normal (New Zealand White, NZW) and Watanabe heritable hyperlipidemic (WHHL) rabbits: the large animal model of familial hypercholesterolemia type IIa (FH). FH is a life-threatening human inherited autosomal disease caused by a mutation in the low-density lipoprotein receptor (LDLR) gene, which leads to severe hypercholesterolemia and premature coronary heart disease. Rabbit hepatocytes were isolated from the resected left liver lobe, and the portal branches of the median lobes were embolized with Histoacryl(r) glue under radiologic guidance. NZW and WHHL hepatocytes were each labeled with Hoechst dye or transduced with lentivirus expressing GFP under the control of a liver-specific promoter (mTTR, a modified murine transthyretin promoter) and were then immediately transplanted back into donor animals. In our conditions, 65-70% of the NZW and WHHL hepatocytes were transduced. Liver repopulation after transplantation with the Hoechst-labeled hepatocytes was 3.5 +/- 2%. It was 1.4 +/- 0.6% after transplantation with either the transduced NZW hepatocytes or the transduced WHHL hepatocytes, which was close to that obtained with Hoechst-labeled cells, given the mean transduction efficacy. Transgene expression persisted for at least 8 weeks posttransplantation. Transduction of WHHL hepatocytes with an LDLR-encoding vector resulted in phenotypic correction in vitro as assessed by internalization of fluorescent LDL ligands. In conclusion, our results have applications for the treatment of inherited metabolic liver diseases, such as FH, by transplantation of lentivirally transduced hepatocytes. PMID- 26858859 TI - Cell Persistence of Allogeneic Keratinocytes and Fibroblasts Applied in a Fibrin Matrix to Acute, Full Thickness Wounds. AB - HP802-247 is a living cell suspension of cultured allogeneic growth-arrested human male keratinocytes and fibroblasts (1:9 ratio), intended for spray application to chronic wounds. In this study, a small wound was created on the arms of 28 healthy female volunteers (3-mm punch), followed by a single application of HP802-247. At each subsequent week for 8 weeks, a punch excision of the wounds was performed on a cohort of three subjects. Excised specimens were analyzed for allogeneic fibroblast and keratinocyte DNA determined by Y chromosome short-tandem repeats using PCR amplification followed by capillary electrophoresis, a method with estimated sensitivity of 1 male cell in a background of 8,000 female cells. A complete haplotype attributable to HP802-247 fibroblasts was detected in three of three samples at 1 week, with one partial and one complete fibroblast haplotype detected at 2 weeks, and one partial keratinocyte haplotype detected at 3 weeks postapplication. The findings indicate that HP802-247 can be expected to persist in an acute wound bed for up to 2 weeks postapplication. PMID- 26858858 TI - Human Decidua-Derived Mesenchymal Cells Are a Promising Source for the Generation and Cell Banking of Human Induced Pluripotent Stem Cells. AB - Placental tissue is a biomaterial with remarkable potential for use in regenerative medicine. It has a three-layer structure derived from the fetus (amnion and chorion) and the mother (decidua), and it contains huge numbers of cells. Moreover, placental tissue can be collected without any physical danger to the donor and can be matched with a variety of HLA types. The decidua-derived mesenchymal cells (DMCs) are highly proliferative fibroblast-like cells that express a similar pattern of CD antigens as bone marrow-derived mesenchymal cells (BM-MSCs). Here we demonstrated that induced pluripotent stem (iPS) cells could be efficiently generated from DMCs by retroviral transfer of reprogramming factor genes. DMC-hiPS cells showed equivalent characteristics to human embryonic stem cells (hESCs) in colony morphology, global gene expression profile (including human pluripotent stem cell markers), DNA methylation status of the OCT3/4 and NANOG promoters, and ability to differentiate into components of the three germ layers in vitro and in vivo. The RNA expression of XIST and the methylation status of its promoter region suggested that DMC-iPSCs, when maintained undifferentiated and pluripotent, had three distinct states: (1) complete X chromosome reactivation, (2) one inactive X-chromosome, or (3) an epigenetic aberration. Because DMCs are derived from the maternal portion of the placenta, they can be collected with the full consent of the adult donor and have considerable ethical advantages for cell banking and the subsequent generation of human iPS cells for regenerative applications. PMID- 26858860 TI - Human Liver Progenitor Cells for Liver Repair. AB - Because of their high proliferative capacity, resistance to cryopreservation, and ability to differentiate into hepatocyte-like cells, stem and progenitor cells have recently emerged as attractive cell sources for liver cell therapy, a technique used as an alternative to orthotopic liver transplantation in the treatment of various hepatic ailments ranging from metabolic disorders to end stage liver disease. Although stem and progenitor cells have been isolated from various tissues, obtaining them from the liver could be an advantage for the treatment of hepatic disorders. However, the techniques available to isolate these stem/progenitor cells are numerous and give rise to cell populations with different morphological and functional characteristics. In addition, there is currently no established consensus on the tests that need to be performed to ensure the quality and safety of these cells when used clinically. The purpose of this review is to describe the different types of liver stem/progenitor cells currently reported in the literature, discuss their suitability and limitations in terms of clinical applications, and examine how the culture and transplantation techniques can potentially be improved to achieve a better clinical outcome. PMID- 26858861 TI - Transplantation of Human Adipose Tissue-Derived Mesenchymal Stem Cells Restores the Neurobehavioral Disorders of Rats With Neonatal Hypoxic-Ischemic Encephalopathy. AB - Improving the effects of human adipose tissue-derived mesenchymal stem cells (ASCs) on the demyelination and neurobehavioral function was investigated in an experimental model of neonatal hypoxic-ischemic encephalopathy (HIE). Seven-day old male rats were subjected to hypoxia-ischemia-lipopolysaccharide and intracerebroventricularly transplanted with human ASCs (4 * 10(5) cells/rat) once at postnatal day 10 (PND10) or repeatedly at PND10, 17, 27, and 37. Neurobehavioral abnormalities (at PND20, 30, and 40) and cognitive functions (at PND41-44) were evaluated using multiple test systems. Human ASCs recovered the using ratio of forelimb contralateral to the injured brain, improved locomotor activity, and restored rota-rod performance of HIE animals, in addition to showing a marked improvement of cognitive functions. It was confirmed that transplanted human ASCs migrated to injured areas and differentiated into oligodendrocytes expressing myelin basic protein (MBP). Moreover, transplanted ASCs restored production of growth and neurotrophic factors and expression of decreased inflammatory cytokines, leading to attenuation of host MBP loss. The results indicate that transplanted ASCs restored neurobehavioral functions by producing MBP as well as by preserving host myelins, which might be mediated by ASCs' anti-inflammatory activity and release of growth and neurotrophic factors. PMID- 26858863 TI - Long-Expected New Start. PMID- 26858862 TI - Phenotype and Stability of Neural Differentiation of Androgenetic Murine ES Cell Derived Neural Progenitor Cells. AB - Uniparental zygotes with two paternal (androgenetic, AG) or two maternal genomes (gynogenetic, GG) cannot develop into viable offsprings but form blastocysts from which pluripotent embryonic stem (ES) cells can be derived. For most organs, it is unclear whether uniparental ES cells can give rise to stably expandable somatic stem cells that can repair injured tissues. Even if previous reports indicated that the capacity of AG ES cells to differentiate in vitro into pan neural progenitor cells (pNPCs) and into cells expressing neural markers is similar to biparental [normal fertilized (N)] ES cells, their potential for functional neurogenesis is not known. Here we show that murine AG pNPCs give rise to neuron-like cells, which then generate sodium-driven action potentials while maintaining fidelity of imprinted gene expression. Neural engraftment after intracerebral transplantation was achieved only by late (22 days) AG and N pNPCs with in vitro low colony-forming cell (CFC) capacity. However, persisting CFC formation seen, in particular, in early (13 or 16 days) differentiation cultures of N and AG pNPCs correlated with a high incidence of trigerm layer teratomas. As AG ES cells display functional neurogenesis and in vivo stability similar to N ES cells, they represent a unique model system to study the roles of paternal and maternal genomes on neural development and on the development of imprinting associated brain diseases. PMID- 26858864 TI - Bioimaging of Transgenic Rats Established at Jichi Medical University: Applications in Transplantation Research. AB - Research in the life sciences has been greatly advanced by the ability to directly visualize cells, tissues, and organs. Preclinical studies often involve many small and large animal experiments and, frequently, cell and organ transplantations. The rat is an excellent animal model for the development of transplantation and surgical techniques because of its small size and ability to breed in small spaces. Ten years ago, we established color-imaging transgenic rats and methods for the direct visualization of their tissues. Since then, our transgenic rats have been used throughout the various fields that are concerned with cell transplantation therapy. In this minireview, we summarize results from some of the groups that have used our transgenic rats at the bench level and in cell transplantation research. PMID- 26858865 TI - ER Stress and beta-Cell Pathogenesis of Type 1 and Type 2 Diabetes and Islet Transplantation. AB - Endoplasmic reticulum (ER) stress affects the pathogenesis of diabetes. ER stress plays important roles, both in type 1 and type 2 diabetes, because pancreatic beta-cells possess highly developed ER for insulin secretion. This review summarizes the relationship between ER stress and the pathogenesis of type 1 and type 2 diabetes. In addition, the association between islet transplantation and ER stress is discussed. PMID- 26858867 TI - Culture Conditions for Mouse Pancreatic Stem Cells. AB - Recently, mouse pancreatic stem cells have been isolated from adult mouse pancreata. However, these pancreatic stem cells could be maintained only under specific culture conditions with lot-limited fetal bovine serum (FBS). For the efficient isolation and maintenance of mouse pancreatic stem cells, it is important to identify culture conditions that can be used independent of the FBS lot. In this study, we evaluated the culture conditions required to maintain mouse pancreatic stem cells. The mouse pancreatic stem cells derived from the pancreas of a newborn mouse, HN#101, were cultured under the following conditions: 1) Dulbecco's modified Eagle's medium (DMEM) with 20% lot-limited FBS, in which mouse pancreatic stem cells could be cultured without changes in morphology and growth activity; 2) complete embryonic stem (ES) cell media; and 3) complete ES cell media on feeder layers of mitomycin C-treated STO cells, which were the same culture conditions used for mouse ES cells. Under culture conditions #1 and #3, the HN#101 cells continued to form a flat "cobblestone" monolayer and continued to divide actively beyond the population doubling level (PDL) 100 without growth inhibition, but this did not occur under culture condition #2. The gene expression profile and differentiated capacity of the HN#101 cells cultured for 2 months under culture condition #3 were similar to those of HN#101 cells at PDL 50. These data suggest that complete ES cell media on feeder layers could be useful for maintaining the undifferentiated state of pancreatic stem cells. PMID- 26858866 TI - A Review of Autologous Islet Transplantation. AB - Autologous islet transplantation after total or semitotal pancreatectomy aims to preserve insulin secretory function and prevent the onset of diabetes. The major indication for pancreatectomy is chronic pancreatitis with severe abdominal pain, a benign pancreatic tumor, and trauma. The metabolic outcome of autologous islet transplantation is better than that of allogeneic transplantation and depends on the number of transplanted islets. Achieving islet isolation from a fibrous or damaged pancreas is one of the biggest challenges of autologous islet transplantation; a major complication is portal vein thrombosis after crude islet infusion. However, the incidence of portal vein thrombosis has decreased as islet preparation techniques have improved over time. PMID- 26858868 TI - Isolation Efficiency of Mouse Pancreatic Stem Cells Is Age Dependent. AB - Mouse pancreatic stem cells have been isolated from mouse pancreata. This study evaluated the efficacy of isolating mouse pancreatic stem cells using mice of different ages. The pancreata of newborn mice, 8-week-old mice, and 24-week-old mice were harvested and digested by using collagenase. The "duct-like" cells in the digested pancreatic tissue were then inoculated into 96-well plates, cloned by limiting dilution, and cultured in DMEM with 20% FBS. Pancreatic stem cells were isolated from the pancreata of all newborn mice, while cells could only be isolated from 10% of the pancreata of 8-week-old mice and could not be isolated from the pancreata of any 24-week-old mice. These data suggest that young mice may have some pancreatic stem cells and that older mice may only have a few pancreatic stem cells. These data also indicate that it is extremely difficult to isolate pancreatic stem cells from older mice, suggesting that future research focus its efforts on finding methods of isolating pancreatic stem cells from adult mice. PMID- 26858869 TI - Use of Mesenchymal Stem Cell-Conditioned Medium to Activate Islets in Preservation Solution. AB - Pancreatic islet transplantation has received widespread attention as a promising treatment for type 1 diabetes. However, islets for transplantation are subject to damage from a number of sources, including ischemic injury during removal and delivery of the donor pancreas, enzymatic digestion during islet isolation, and reperfusion injury after transplantation in the recipient. Here we found that protein fractions secreted by mesenchymal stem cells (MSCs) were capable of activating preserved islets. A conditioned medium from the supernatant obtained by culturing adipose tissue MSCs (derived from wild-type Lewis rats) was prepared for 2 days in serum-free medium. Luc-Tg rat islets to which an organ preservation solution was added were then incubated at 4 degrees C with fractions of various molecular weights prepared from the conditioned medium. Under the treatment with some of the fractions, by 4 days the relative luminescence intensities (representative of the ATP levels of the cold-preserved islets) had increased to over 150% of their initial values. Our novel system may be able to restore isolated islets to the condition they were in before transport, culture, and transplantation. PMID- 26858870 TI - Inhibition of Hepatic Ischemic Reperfusion Injury Using Saline Exposed to Electron Discharge in a Rat Model. AB - The pathogenesis of ischemia/reperfusion (I/R) injury in surgical trauma, organ transplantations, and brain and myocardial infarctions is attributable to excessive oxidative stress caused by reactive oxygen species and their metabolites. We prepared a physiological saline solution treated with simple exposure to a microampere current with electron discharge onto the surface; this treatment increased reduction potential and caused proton reduction. We examined the reductive potency of the electron-treated solution (ETS) on hepatocellular I/R injury in a rat model. When the ETS was administered in four doses at 0, 3, 10, and 20 min after reperfusion, severe hepatocellular injury was suppressed, as revealed by a decrease in serum alanine aminotransferase levels and histopathological improvement of liver damage. Since a preparation of hydrogen gas-dissolved saline solution (HDS) was shown to be capable of suppressing I/R injury, the possible involvement of dissolved hydrogen gas in the effectiveness of ETS was examined. When HDS was treated by degasification, the aforementioned effectiveness was decreased. In contrast, the same treatment did not alter the effectiveness of ETS. These results suggest that the antioxidative efficacy of ETS is not attributable to dissolved hydrogen gas but presumably to the molecule(s) produced from the stepwise reduction of protons in the solution. PMID- 26858871 TI - Observation of Positively Charged Magnetic Nanoparticles Inside HepG2 Spheroids Using Electron Microscopy. AB - Magnetic resonance imaging (MRI) using magnetic nanoparticles has been used to diagnose vascular diseases as well as to monitor transplanted cells and tissues. In this study, we synthesized magnetic iron oxide nanoparticles (TMADM-03), electrically charged by the presence of a cationic end-group substitution of dextran, and observed these nanoparticles inside three-dimensional models of HepG2 spheroids, which mimic tissues. Patterned cell array glass disks were prepared to visualize the presence of TMADM-03 uptaken by HepG2 spheroids using transmission electron microscopy (TEM). The HepG2 cells (2 * 10(5) cells) were inoculated onto Cell-ableTM 12-well plates. After 48 h of culture, the cells were incubated with 75 ug Fe/ml TMADM-03 in culture medium for 24 h. To investigate the cellular function of the HepG2 spheroids, the albumin secretion was evaluated by an ELISA. The albumin secretion after incubation for 24 h was reduced compared with the secretion prior to the addition of TMADM-03. TEM image samples were prepared in a planar direction or a vertical direction to the HepG2 spheroids on patterned cell array glass disks. The incorporation of TMADM-03 inside the HepG2 spheroids was confirmed. In addition, TMADM-03 could be observed in the deeper layers of the spheroids, and this was localized in the lysosomes. These data suggest that the novel magnetic iron oxide nanoparticles invade three-dimensional HepG2 spheroids. PMID- 26858872 TI - Improved Recovery of Hepatocytes Isolated From Warm Ischemic Rat Liver by Citrate Phosphate Dextrose (CPD)-Supplemented Euro-Collins Solution. AB - Demand for human primary hepatocytes is increasing, particularly for clinical trials of hepatocyte transplantation. However, due to the severe shortage of organ transplant donors, the source of cells for these endeavors is restricted to untransplantable livers, such as those from non-heart-beating donors and surgically resected liver tissues. To improve cell recovery from such sources after warm ischemia, we evaluated the efficacy of applying perfusion solutions, focusing on improvement of hepatocyte recovery. Warm ischemia was induced by clamping both portal vein and hepatic artery for 10 or 15 min in rats. The liver was perfused with either Euro-Collins (EC) or extracellular-type trehalose containing Kyoto (ETK) solutions supplemented with an anticoagulant, either heparin or citrate phosphate dextrose solution (CPD), compared to Ca(2+), Mg(2+) free Hanks solution. While the viability of recovered cells was 81.5 +/- 4.2% and cell yield was 2.27 +/- 0.53 * 10(8) in nonwarm ischemia controls (n = 11), these values were only 74.7 +/- 2.9% and 0.38 +/- 0.17 * 10(8), respectively, in the 10 min warm ischemia group, using the Hanks as the perfusion solution. Although the addition of heparin increased the live cell number only twofold (0.71 +/- 0.40 * 10(8), n = 4), the best improvement was achieved by adding CPD to EC. This resulted in a recovery of 1.41 +/- 0.50 * 10(8) in the 10-min ischemia group (n = 7) and 1.37 +/- 0.28 * 10(8) in the 15-min group (n = 3). Macroscopic observation showed that blood had been completely flushed out by the solution, suggesting good restoration of the microcirculation in ischemic liver. Using ETK instead of EC resulted in a slight decrease in efficacy. These results demonstrate that CPD, as opposed to heparin, is effective in ensuring liver microcirculation and flushing out the blood and that EC is the best perfusion solution for obtaining hepatocytes from ischemic liver. PMID- 26858873 TI - Organ Biology-New Development. PMID- 26858874 TI - Comparison of New Preservation Solutions, HN-1 and University of Wisconsin Solution, in Pancreas Preservation for Porcine Islet Isolation. AB - For pancreatic islet transplantation, maintaining organ viability after pancreas procurement is critical and a major determinant for better graft function and survival. University of Wisconsin (UW) solution is currently the gold standard for abdominal organ preservation and the pancreas in particular. However, in the use of UW preservation solution for islet transplantation, there are disadvantages to be overcome, such as the inhibition of collagenase activity during pancreatic digestion. In this study, we compared UW solution with HN-1 solution in pancreas preservation for islet isolation. Islet yield was significantly greater in the HN-1 group than the UW group both before and after purification. In the in vitro assay, the adenosine triphosphate content in cultured islets was significantly higher in the HN-1 group than in the UW group. Furthermore, in streptozotocin-induced diabetic nude mice, the islet graft function of the HN-1 group was superior to that of the UW group. We concluded that the use of HN-1 solution is a promising approach for optimal pancreas preservation in islet transplantation. PMID- 26858875 TI - Comparison of Incubation Solutions Prior to the Purification of Porcine Islet Cells. AB - For pancreatic islet transplantation, one of the most important steps of islet isolation is islet purification. The most common method of islet purification is density gradient centrifugation because there are differences in density between islets and acinar tissue. However, the density of islets/acinar tissue depends on several conditions, such as the incubation time before purification and the osmolality of the preincubation solution. In this study, we evaluated the impact of using two different preincubation solutions before purification. We used the University of Wisconsin (UW) solution and a new preservation solution (HN-1), which we recently developed. There were no significant differences between the two solutions in terms of the islet yield, rate of viability, and purity or stimulation index after purification. There were also no differences in the attainability and suitability of posttransplantation normoglycemia. Our study shows that the HN-1 solution is equivalent to the UW solution for preincubation before islet purification. PMID- 26858876 TI - Maintenance of Viability and Function of Rat Islets With the Use of ROCK Inhibitor Y-27632. AB - The number of patients with diabetes is on an increasing trend, thus leading to the belief that diabetes will be the largest medical problem of the 21st century. Islet transplantation can improve glycometabolic control in patients with type 1 diabetes. We studied the viability of Rho-associated protein kinase (ROCK) inhibitor Y-27632 in a culture system in vitro on freshly isolated rat islets. Islet isolation was conducted on a Lewis rat, and studies of culture solutions were split into two groups, one group using ROCK inhibitor Y-27632, and another without. On the seventh day of culture, we evaluated the differences for the cell morphology, viability, and insulin secretion. The Y-27632 group maintained form better than the group without Y-27632. With strong expression of Bcl-2 observed with the Y-27632 group, and expression suppressed with Bax, inhibition of apoptosis by Y-27632 was confirmed. The Y-27632 group predominantly secreted insulin. For islet transplantation, Y-27632 inhibited cell apoptosis in a graft and was also effective in promoting insulin secretion. We were able to confirm effective morphological and functional culture maintenance by separating islets from a rat and adding ROCK inhibitor Y-27632 to the medium. PMID- 26858877 TI - Development of Canine Models of Type 1 Diabetes With Partial Pancreatectomy and the Administration of Streptozotocin. AB - We created canine models of type 1 diabetes that were suitable for the assessment of cell therapies, such as islet transplantation and bioartificial pancreas, with low-dose streptozotocin (STZ) injection and partial pancreatectomy. In our model, a 50% pancreatectomy was performed with general anesthesia, followed by systemic injection of 35 mg/kg STZ into a vein of the foreleg. Four weeks after the administration of STZ, the fasting blood glucose level of our model dogs was found to be over 200 mg/dl twice on different days, and we could not detect any canine insulin by the intravenous glucose tolerance test (IVGTT). We therefore diagnosed the dogs to have induced diabetes. Some studies have reported high-dose STZ to be very toxic for both the kidney and liver, and therefore a lower dose is desirable to induce diabetic models without any associated kidney or liver damage. We think that the combination of a partial pancreatectomy can thus make it possible to reduce the dose of STZ, and it is therefore useful for the creation of type 1 diabetes models. We believe that our model is a safe and reliable model for type 1 diabetes in canines to assess the efficacy of pancreas targeted cell therapies. PMID- 26858878 TI - Quality of Air-Transported Human Islets for Single Islet Cell Preparations. AB - In new generation medical therapies for type 1 diabetes mellitus (DM), cell-based approaches using pancreatic islets have attracted significant attention worldwide. In particular, dispersed islet cells obtained from isolated pancreatic islets have been a valuable source in the cell biology and tissue engineering fields. Our experimental approach to the development of new islet-based DM therapies consisted of creating a monolithic islet cell sheet format using dispersed islet cells. In this experiment, we explored the potential of internationally transporting human islets from Alberta, Canada to Tokyo, Japan and obtaining viable dispersed islet cells. A total of 34 batches of isolated and purified human islets were transported using a commercial air courier service. Prior to shipping, the human islets had been in culture for 0-108 h at the University of Alberta. The transportation period from Alberta to Tokyo was 2-5 days. The transported human islet cells were enzymatically dispersed as single cells in Tokyo. The number of single islet cells decreased as the number of transportation days increased. In contrast, cell viability was maintained regardless of the number of transportation days. The preshipment culture time had no effect on the number or viability of single cells dispersed in Tokyo. When dispersed single islet cells were plated on laminin-5-coated temperature responsive polymer-grafted culture dishes, the cells showed favorable attachment followed by extension as a monolithic format. The present study demonstrated that long-distance transported human islets are a viable cell source for experiments utilizing dispersed human islet cells. PMID- 26858879 TI - Comparison of the Pharmacological Efficacies of Immunosuppressive Drugs Evaluated by the ATP Production and Mitochondrial Activity in Human Lymphocytes. AB - The lymphocyte immunosuppressant sensitivity test (LIST) using patient peripheral lymphocytes can predict the therapeutic efficacy of immunosuppressive drugs used in renal transplantation. We have evaluated the pharmacological efficacy of drugs by using the LIST with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, which measures the cellular mitochondrial activity. The LIST with the MTT assay requires a relatively large amount of blood. As such, we developed a new assay for examining drug sensitivity with a CellTiter-Glo assay, which measures the amount of cellular ATP to help increase the assay's sensitivity and reduce the amount of blood needed. Renal transplant recipients generally receive either cyclosporine or tacrolimus, in addition to mycophenolate mofetil and methylprednisolone, as an immunosuppressive therapy to prevent acute rejection. We evaluated the pharmacological efficacy of these immunosuppressive agents with both the MTT and CellTiter-Glo assays using the peripheral blood mononuclear cells of 21 healthy volunteers. Furthermore, we also examined the relationship between these immunosuppressive agents' pharmacological efficacy and the results of the MTT and CellTiter-Glo assays. The IC50 values for cyclosporine, tacrolimus, mycophenolic acid, and methylprednisolone were significantly correlated between the MTT and CellTiter-Glo assays. The amount of blood cells required for LIST with the CellTiter-Glo assay was able to be reduced to 25% of the amount required for the previously established LIST with the MTT assay procedure. We concluded from these observations that the LIST with the CellTiter-Glo assay should be used instead of the MTT assay for carrying out individualized immunosuppressive therapy in renal transplantation patients. PMID- 26858880 TI - Peripheral Lymphocyte Response to Mycophenolic Acid In Vitro and Incidence of Cytomegalovirus Infection in Renal Transplantation. AB - The lymphocyte immunosuppressant sensitivity test (LIST) with 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay procedure has been used to predict the pharmacological efficacy of immunosuppressive agents to prevent acute rejection episodes for renal transplant recipients. In this study, mycophenolic acid (MPA) pharmacological efficacies were evaluated by LIST at both prior to and just after renal transplantation. We compared the efficacies to the clinical outcome of these recipients. MPA's pharmacological efficacy was evaluated by LIST not only before the operation but also at 2, 4, and 6 weeks after transplantation in 16 renal transplant recipients. These recipients were divided into high- and low-sensitivity groups according to peripheral blood mononuclear cell (PBMC) sensitivity to MPA in vitro. The MPA sensitivities were compared to cytomegalovirus (CMV) infection and acute rejection episodes in these recipients under MPA immunosuppressive therapy. The rate of CMV infection episodes in the low-MPA pharmacological efficacy group categorized at 2 weeks after renal transplantation was 5/6 (83.3%), which was significantly higher than the rate of 1/10 (10.0%) (p < 0.01) in the high-MPA sensitivity group. However, the MPA pharmacological efficacy evaluated both before and after transplantation had no relationship with the incidence of rejection episodes. These findings suggest that the MPA pharmacological efficacy evaluated by LIST at 2 weeks after operation is a useful biomarker for predicting the following occurrence of CMV infection episodes in renal transplant recipients. PMID- 26858881 TI - Experimental Nonalcoholic Steatohepatitis Induced by Neonatal Streptozotocin Injection and a High-Fat Diet in Rats. AB - Nonalcoholic steatohepatitis (NASH) has become a major concern in clinical hepatology. To elucidate the disease mechanisms and to develop a treatment, the advent of an appropriate experimental model is crucial. Pregnant Sprague-Dawley rats were fed a high-fat diet from gestational day 16. Two days after birth, the neonates were injected subcutaneously with streptozotocin (STZ) (180, 200, or 256 mg/kg). The mothers were fed a high-fat diet during the nursing period. After being weaned (4 weeks of age), the juvenile rats were fed the same high-fat diet. The survival rates at the time of weaning were 25.6% (180 mg/kg STZ), 22.8% (200 mg/kg STZ), and 19.4% (256 mg/kg STZ). The mean body weight of NASH rats was approximately 20% less than that of normal rats. Serum levels of glucose, alanine aminotransferase, and hyaluronic acid increased in NASH rats. Histologically, typical features of steatohepatitis such as ballooning, inflammatory cell infiltration, and perivenular and pericellular fibrosis were observed. In an indocyanine green loading test, the blood half-life was significantly longer in NASH rats (5.04 +/- 2.14 vs. 2.72 +/- 0.72 min; p < 0.05), which was suggestive of an impaired hepatobiliary transportation function. Concomitantly, biliary ICG concentrations in NASH rats stabilized in a delayed fashion compared with normal rats. In addition, the amount of bile excreted in NASH rats was significantly lower than that in normal rats (4.32 +/- 0.83 vs. 7.66 +/- 1.05 mg/min; p < 0.01). The rat NASH model presented here mimics the clinical features of the disease and will be a helpful tool for medical and bioscience research. PMID- 26858882 TI - Electron Therapy Attenuated Elevated Alanine Aminotransferase and Oxidative Stress Values in Type 2 Diabetes-Induced Nonalcoholic Steatohepatitis of Rats. AB - Chronic oxidative stress plays a key role in the progression of nonalcoholic steatohepatitis (NASH). We examined the efficacy of antioxidative electron treatment on type 2 diabetes-induced NASH in a rat model. We established NASH model rats, induced by neonatal administration of streptozotocin and a high-fat diet, which exhibited pathologically high values of alanine aminotransferase (ALT), glucose, and malondialdehyde (MDA). The rats were exposed to electron discharge at very low energy for 4 weeks; this dose results in the reduction of Fe(3+) and glutathione disulfide in vitro. Serum ALT values were increased from baseline (8 weeks) to 125.0 +/- 13 U/L at 10 weeks in the control group. In contrast, the values in the treated group did not show any increase at 10 weeks [87 +/- 10 U/L (p = 0.0391)]. Hepatic MDA levels were also significantly decreased at 12 weeks (p < 0.05), but 8-hydroxy-2'-deoxyguanosine values were not statistically significant (p = 0.076). A gradual but steadily decreasing trend from initially high glucose levels was observed, though the values were not significant in 12-week-old animals (p = 0.074). However, the serum values of MDA, ALT, and glucose were well correlated. The progression of fibrosis as measured by increased serum levels of hyaluronic acid and histological examinations were not affected by the treatment in this model. Antioxidative electron treatment at very low energy attenuated the pathogenically elevated liver inflammation and oxidative stress, together with presumably impaired glucose metabolism in NASH rat model. PMID- 26858883 TI - STO Feeder Cells Are Useful for Propagation of Primarily Cultured Human Deciduous Dental Pulp Cells by Eliminating Contaminating Bacteria and Promoting Cellular Outgrowth. AB - STO feeder cells, a line established from mouse SIM embryonic fibroblasts, have been frequently used for establishing embryonic stem cells and maintaining them in an undifferentiated state. There are some reports demonstrating that fibroblastic cells have the ability to phagocytose Gram-positive bacterium (e.g., streptococci and staphylococci). In this study, we examined the possibility that STO cells could phagocytose Streptococcus mutans (a bacteria causing tooth decay), which always contaminates cultures of primarily isolated human deciduous dental pulp cells (HDDPCs). Simple cultivation of the primary HDDPCs in the absence of STO cells allowed S. mutans to massively propagate in the medium, thus leading to an opaque medium. In contrast, there was no bacterial contamination in the cultures containing mitomycin C (MMC)-inactivated STO cells. Furthermore, STO cells indicated bacterial phagocytic activity under fluorescent microscopy with the dye pHrodo. Besides removal of contaminating bacteria, STO feeder cells allowed the HDDPCs to spread out. These data suggest that MMC-treated STO cells can be useful for propagation of HDDPCs by eliminating contaminating bacteria and by promoting cellular outgrowth. PMID- 26858884 TI - Induced Pluripotent Stem Cell Labeling Using Quantum Dots. AB - Induced pluripotent stem (iPS) cells have received remarkable attention as the cell sources for clinical applications of regenerative medicine including stem cell therapy. Additionally, labeling technology is in high demand for tracing transplanted cells used in stem cell therapy. In this study, we used quantum dots (QDs), which have distinct fluorescence abilities in comparison with traditional probes, as the labeling materials and investigated whether iPS cells could be labeled with QDs with no cytotoxicity. iPS cells could not be labeled with QDs alone but required the use of cell-penetrating peptides such as octaarginine (R8). No significant cytotoxicity to iPS cells was confirmed by up to 8 nM QDs, and the iPS cells labeled with QDs maintained their undifferentiated state and pluripotency. These data suggest that QDs can be used for fluorescence labeling of iPS cells. PMID- 26858885 TI - Adipose Tissue-Derived Stem Cell Imaging Using Cadmium-Free Quantum Dots. AB - Quantum dots (QDs) have received much attention for biomolecule and cell imaging applications because of their superior optical properties such as high quantum efficiency, size-tunable emission, and resistance to photobleaching process. However, QDs that are commercially available contain cadmium (Cd), a highly toxic element. Thus, the development of Cd-free and less toxic QDs is strongly desired. In this study, we developed Cd-free QDs (ZnS-coated ZnS-AgInS2 solid solution nanoparticles with a sulfo group: ZnS-ZAIS-SO3H) and investigated the ability of this material to label stem cells. ZnS-ZAIS-SO3H could be transduced into mouse adipose tissue-derived stem cells (mASCs) using octaarginine peptides (R8), known as cell-penetrating peptides. The optimal ratio of ZnS-ZAIS-SO3H:R8 was found to be 1:100 for labeling mASCs. More than 80% of mASCs labeled with 500 nM ZnS-ZAIS SO3H were found to be alive, and the proliferation rates of labeled mASCs were maintained at the same rate as that of nonlabeled mASCs. In addition, no abnormalities in the morphology of mASCs labeled with ZnS-ZAIS-SO3H could be observed. These data suggest that ZnS-ZAIS-SO3H may be effective for the labeling of mASCs. PMID- 26858886 TI - Autologous Skeletal Myoblast Sheet Therapy for Porcine Myocardial Infarction Without Increasing Risk of Arrhythmia. AB - Safety concerns of ventricular tachyarrhythmia have arisen from some clinical trials of autologous skeletal myoblast (SkM) injection therapy. This study examined the effect and safety of SkM sheet therapy in a pig model of chronic myocardial infarction. Minipigs underwent LAD occlusion using a balloon catheter for 2 h, followed by reperfusion. After 28 days, 12 SkM sheets were transplanted onto the infarcted myocardium (sheet group n = 8); the same number of cells was also injected into the myocardium (injection group n = 7), and sham operations were performed as a control (sham group n = 7). Implantable ECG loop recorders (ILR) were placed subcutaneously on the left thorax. At 28 days after transplantation, we assessed cardiac function with MDCT, interrogated ILR, and performed programmed ventricular stimulation (PVS), after which organs were harvested for histopathology. To assess the inflammatory and injury response, inflammation factors and high-sensitive CRP and troponin I were measured at 1, 3, 7, and 28 days after transplantation by the cytokine array method and ELISA, respectively. The sheet group showed an improvement in cardiac function compared with both the injection and sham groups (LVEF change: 5.8 +/- 2.7%, -1.0 +/- 2.6%, and -3.8 +/- 1.8% in the sheet, injection, and sham groups, respectively, p < 0.05). VF was not detected in any group using ILR, while VT was detected in one pig from the injection group. VF was induced in 25.0%, 71.4%, and 28.6% of animals in the sheet, injection, and sham groups, respectively. In the injection group, anti-macrophage-positive cells were observed around the injected cells within the myocardium. Transmission electron microscopic images showed differentiated myofilaments, collagen layers, and a characteristic extracellular matrix surrounding the SkMs in the sheet group. Toroponin I and IL-6 levels were higher in the injection group compared with both the sheet and sham groups. SkM sheets transplanted onto infarcted myocardium improved cardiac function over SkM injection without increasing arrhythmogenicity. PMID- 26858887 TI - Disease and Stem Cell-Based Analysis of the 2013 ASNTR Meeting. AB - A wide diversity of subjects are presented at the annual American Society of Neural Therapy and Repair meeting every year, and 2013 was no exception. An insight into the current research trends in regenerative medicine was provided, including studies to elucidate disease mechanisms and the means to treat them. Different methods featured in 2013 included stem cell and tissue transplantation, gene therapy, dietary supplementation, and hydrogels as scaffold systems for the growth of stem cells. Diseases ranged from Parkinson's disease, spinal cord injury, and stroke to traumatic brain injury, pain, and epilepsy. Traumatic brain injury was an increasingly popular topic, highlighting the concerns of soldiers returning from duty overseas. A number of studies looked at ways to treat or elucidate mechanisms for more than one disorder. The studies including stem cells predominantly involved human-derived cells being transplanted, and the most common recipient of stem cells were rodents. Only one autologous transplant study, which featured mouse bone marrow cells being transplanted into mice for the treatment of stroke, was presented this year. The most popular stem cell studied was the neural stem cell, which in some instances was predifferentiated from induced pluripotent stem cells or embryonic stem cells. Other stem cells included the mesenchymal stem cell and adipose, amniotic fluid, and umbilical cord blood-derived cells. Many studies also looked at more than one stem cell type. Combinational studies, such as gene therapy and transplantation, were also commonly explored as well as studies using fetal ventral mesencephalon or spinal cord tissue rather than stem cells. Numerous studies also featured the use of "drugs"-some naturally derived or naturally occurring as well as drug cocktails. A number of possible treatments, including physical therapy and socialization, were explored for a number of different diseases, as well as reports on the current status of four gene therapy clinical trials for the treatment of Parkinson's disease. Other studies assessed possible causes of specific disorders. In this way, the ASNTR provides an important snapshot of developments in the field of regenerative medicine. PMID- 26858889 TI - Integration-Free Human Induced Pluripotent Stem Cells From Type 1 Diabetes Patient Skin Fibroblasts Show Increased Abundance of Pancreas-Specific microRNAs. AB - Type 1 diabetes (T1D) is a disease that is typically associated with multigenetic changes as well as environmental triggers. Disease-specific induced pluripotent stem cells (iPSCs) are preferable cell sources to study T1D, as they are derived from patient cells and therefore capture the disease genotype in a stem cell line. The purpose of this study was to generate integration-free iPSCs from adult skin fibroblasts with T1D. iPSCs were generated by transfection of synthetic mRNAs encoding transcription factors OCT4, SOX2, KLF4, c-MYC, and LIN28. Phase contrast microscopy, immunocytochemistry, karyotyping, bisulfite genomic sequencing, reverse transcription-polymerase chain reaction, and teratoma formation assay were used to determine reprogramming efficiency, pluripotency, and differentiation potential. Following 18 consecutive days of synthetic mRNA transfections, the T1D patient skin fibroblasts underwent morphological changes, and the aggregated clumps exhibited a human embryonic stem cell (ESC)-like morphology with a high nucleus/cytoplasm ratio. Highly efficient generation of iPSCs was achieved using the mRNA reprogramming approach. The disease-specific iPSCs expressed pluripotency markers, maintained a normal karyotype, and formed teratomas containing tissues representative of the three germ layers when injected into immune-deficient mice. Of interest, the iPSCs showed upregulations of pancreas-specific microRNAs, compared with parental fibroblasts. These data indicate that T1D patient skin fibroblasts can be reprogrammed to pluripotency using a synthetic mRNA approach. These cells can serve as a useful tool for the identification of genes that are involved in autoimmune reactions as well as generating patient-matched beta-cells for cell-based therapy. PMID- 26858888 TI - Application of Induced Pluripotent Stem Cells in Liver Diseases. AB - Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease. PMID- 26858890 TI - Human Menstrual Blood-Derived Mesenchymal Cells as New Human Feeder Layer System for Human Embryonic Stem Cells. AB - Human embryonic stem cells (hESCs) in general require coculture with feeder layers in order to remain undifferentiated. However, the use of animal-derived feeder layers is incompatible with the clinical setting. The objective of this work was to investigate whether human menstrual blood-derived mesenchymal cells (MBMCs) can substitute mouse embryonic fibroblasts (MEFs) as a feeder layer for H9-hESCs. Both feeder cell types were isolated and cultured in DMEM F-12 and high glucose DMEM, respectively. After three passages, they were inactivated with mitomycin C. To test MBMC feeder layer capacity, hESCs were grown over MBMCs and MEFs under standard conditions. hESC growth, proliferation, survival, and maintenance of the undifferentiated state were evaluated. hESCs grown over MBMCs preserved their undifferentiated state presenting standard morphology, expressing alkaline phosphatase, transcription factors OCT3/4, SOX2, and NANOG by RT-PCR and SSEA-4 and OCT3/4 by immunofluorescence assays. It is noteworthy that none of the feeder cells expressed these proteins. The average colony size of the hESCs on MBMCs was higher when compared to MEFs (p < 0.05; mean +/- SD, n = 3). Growth factor analysis revealed amplification of the transcripts for FGF-2, BMP4, TGF beta, VEGF, and PEDF by RT-PCR in MBMCs and MEFs before and after inactivation. Furthermore, similar embryoid body formation, size, and morphology were observed in both feeder layers. In addition, EBs expressed marker genes for the three germ layers cultured on both feeder cells. In conclusion, MBMCs are able to maintain hESCs in an undifferentiated state with comparable efficiency to MEFs. Therefore, MBMCs are a suitable alternative to animal-derived feeder layers for growing hESCs. PMID- 26858892 TI - Basic and Clinical Science for Organ Biology. PMID- 26858891 TI - Preculturing Islets With Adipose-Derived Mesenchymal Stromal Cells Is an Effective Strategy for Improving Transplantation Efficiency at the Clinically Preferred Intraportal Site. AB - We have recently shown that preculturing islets with kidney-derived mesenchymal stromal cells (MSCs) improves transplantation outcome in streptozotocin-diabetic mice implanted with a minimal mass of islets beneath the kidney capsule. In the present study, we have extended our previous observations to investigate whether preculturing islets with MSCs can also be used to enhance islet function at the clinically used intraportal site. We have used MSCs derived from adipose tissue, which are more readily accessible than alternative sources in human subjects and can be expanded to clinically efficacious numbers, to preculture islets throughout this study. The in vivo efficacy of grafts consisting of islets precultured alone or with MSCs was tested using a syngeneic streptozotocin diabetic minimal islet mass model at the clinically relevant intraportal site. Blood glucose concentrations were monitored for 1 month. The vascularization of islets precultured alone or with MSCs was investigated both in vitro and in vivo, using immunohistochemistry. Islet insulin content was measured by radioimmunoassay. The effect of preculturing islets with MSCs on islet function in vitro was investigated using static incubation assays. There was no beneficial angiogenic influence of MSC preculture, as demonstrated by the comparable vascularization of islets precultured alone or with MSCs, both in vitro after 3 days and in vivo 1 month after islet transplantation. However, the in vitro insulin secretory capacity of MSC precultured islets was superior to that of islets precultured alone. In vivo, this was associated with improved glycemia at 7, 14, 21, and 28 days posttransplantation, in recipients of MSC precultured islets compared to islets precultured alone. The area of individual islets within the graft-bearing liver was significantly higher in recipients of MSC precultured islets compared to islets precultured alone. Our experimental studies suggest that preculturing islets with MSCs represents a favorable strategy for improving the efficiency of clinical islet transplantation. PMID- 26858893 TI - Synergistic Effects of Calcineurin Inhibitors and Steroids on Steroid Sensitivity of Peripheral Blood Mononuclear Cells. AB - The steroid receptor (SR) complex contains FKBP51 and FKBP52, which bind to tacrolimus (TAC) and cyclophilin 40, which, in turn, bind to cyclosporine (CYA); these influence the intranuclear mobility of steroid-SR complexes. Pharmacodynamic interactions are thought to exist between steroids and calcineurin inhibitors (CNIs) on the SR complex. We examined the effect of CNIs on steroid sensitivity. Methylprednisolone (MPSL) sensitivity was estimated as the concentration inhibiting mitosis in 50% (IC50) of peripheral blood mononuclear cells and as the area under the MPSL concentration-proliferation suppressive rate curves (CPS-AUC) in 30 healthy subjects. MPSL sensitivity was compared between the additive group (AG) as the MPSL sensitivity that was a result of addition of the proliferation suppressive rate of CNIs to that of MPSL and the mixed culture group (MCG) as MPSL sensitivity of mixed culture with both MPSL and CNIs in identical patients. IC50 values of MPSL and cortisol sensitivity were examined before and 2 months after CNI administration in 23 renal transplant recipients. IC50 and CPS-AUC values of MPSL were lower in the MCG than in the AG with administration of TAC and CYA. The CPS-AUC ratio of MCG and AG was lower in the TAC group. IC50 values of MPSL and cortisol tended to be lower after administration of TAC and CYA, and a significant difference was observed in the IC50 of cortisol after TAC administration. Steroid sensitivity increased with both TAC and CYA. Furthermore, TAC had a greater effect on increasing sensitivity. Thus, concomitant administration of CNIs and steroids can increase steroid sensitivity. PMID- 26858894 TI - Improvement of Infusion Process in Cell Transplantation: Effect of Shear Stress on Hepatocyte Viability Under Horizontal and Vertical Syringe Orientation. AB - Improving cell viability and function are important for enhancing the clinical results of cell transplantation. The relationship between cell viability and shear stress remains unexplained, and sedimentation effects during the infusion process are important to the hepatocyte transplantation process. In the present study, the relationship between cell viability and shear stress in the presence of sedimentation effect was investigated using a microchannel simulating the cell transplantation process under several shear stress conditions. Horizontal and vertical syringe orientations were employed to investigate the sedimentation effect. The vertical syringe orientation resulted in lower viability loss than the horizontal orientation. In summary, removing a sedimentation effect is important to improving cell viability by preventing high shear stress. PMID- 26858895 TI - Three-Dimensional In Vitro Hepatic Constructs Formed Using Combinatorial Tapered Stencil for Cluster Culture (TASCL) Device. AB - Attempts to create artificial liver tissue from various cells have been reported as an alternative method for liver transplantation and pharmaceutical testing. In the construction of artificial liver tissue, the selection of the cell source is the most important factor. However, if an appropriate environment (in vitro/in vivo) cannot be provided for various cells, it is not possible to obtain artificial liver tissue with the desired function. Therefore, we focused on the in vitro environment and produced liver tissues using MEMS technology. In the present study, we report a combinatorial TASCL device to prepare 3D cell constructs in vitro. The TASCL device was fabricated with an overall size of 10 mm * 10 mm with microwells and a top aperture (400 um * 400 um, 600 um * 600 um, 800 um * 800 um) and bottom aperture (40 um * 40 um, 80 um * 80 um, 160 um * 160 um) per microwell. The TASCL device can be easily installed on various culture dishes with tweezers. Using plastic dishes as the bottom surface of the combinatorial TASCL device, 3D hepatocyte constructs of uniform sizes (about phi 100 MUm-phi 200 MUm) were produced by increasing the seeding cell density of primary mouse hepatocytes. The 3D hepatocyte constructs obtained using the TASCL device were alive and secreted albumin. On the other hand, partially adhered primary mouse hepatocytes exhibited a cobblestone morphology on the collagen coated bottom of the individual microwells using the combinatorial TASCL device. By changing the bottom substrate of the TASCL device, the culture environment of the cell constructs was easily changed to a 3D environment. The combinatorial TASCL device described in this report can be used quickly and simply. This device will be useful for preparing hepatocyte constructs for application in drug screening and cell medicine. PMID- 26858896 TI - Influence of Autofluorescence Derived From Living Body on In Vivo Fluorescence Imaging Using Quantum Dots. AB - Quantum dots (QDs) are thought to be a novel inorganic probe for in vivo fluorescence imaging because of their excellent fluorescence properties. Autofluorescence is generally known to be produced from various living bodies including humans, rats, and mice. However, the influence of the autofluorescence on in vivo fluorescence imaging using QDs remains poorly understood. In this article, we assessed the autofluorescence derived from a mouse body and the influence of the autofluorescence on in vivo fluorescence imaging using QDs. The dorsal and ventral autofluorescence derived from a mouse from which the hair was removed were detected under all kinds of excitation/fluorescence filter settings (blue, green, yellow, red, deep red, and NIR) using the MaestroTM in vivo imaging system. The degree of autofluorescence was found to be extremely high in the red filter condition, but transplanted ASCs labeled with QDs on the back of a mouse could be detected in the red filter condition. Moreover, the ASCs labeled with QDs could be traced for at least 5 days. We suggest that fluorescence imaging using QDs can be useful for the detection of transplanted cells. PMID- 26858897 TI - Potential Factors for the Differentiation of ESCs/iPSCs Into Insulin-Producing Cells. AB - The low efficiency of in vitro differentiation of human embryonic stem cells (ESCs) or human induced pluripotent stem cells (iPSCs) into insulin-producing cells thus creates a crucial hurdle for the clinical implementation of human pluripotent stem cells (PSCs). In this study, we investigated the key factors for the differentiation of PSCs into insulin-producing cells. We obtained microarray data of HUES8 and HUES6 from two GeneChips (GPL3921: Affymetrix HT Human Genome U133A Array, GPL570: Affymetrix Human Genome U133 Plus 2.0 Array) in a database of GEO (NCBI), since HUES8 can differentiate into pancreatic cells, while HUES6 hardly demonstrates any differentiation at all. The genes with more than fourfold higher expressions in HUES8 compared to HUES6 included RPS4Y1, DDX3Y, EIF1AY, GREM1, GATA6, and NLGN4Y. Since there were four genes, RPS4Y1, DDX3Y, EIF1AY, and NLGN4Y, on the Y chromosome and HUES8 was a male cell line and HUES6 was a female cell line, we excluded these genes in this study. On the other hand, genes with more than fourfold higher expressions in HUES6 compared to HUES8 included NLRP2, EGR1, and SMC3. We next compared iPSCs derived from pancreatic cells (PiPSCs) and iPSCs derived from fibroblasts (FiPSCs). PiPSCs differentiated into insulin producing cells more easily than FiPSCs because of their epigenetic memory. The gene expressions of GREM1, GATA6, NLRP2, EGR1, and SMC3 in PiPSCs and FiPSCs were also investigated. The expression level of GREM1 and GATA6 in PiPSCs were higher than in FiPSCs. On the other hand, EGR1, which was lower in HUES8 than in HUES6, was predictably lower in PiPSCs than FiPSCs, while NLRP2 and SMC3 were higher in PiPSCs than FiPSCs. These data suggest that the expression of GATA6 and GREM1 and the inhibition of EGR1 may be important factors for the differentiation of PSCs into insulin-producing cells. PMID- 26858898 TI - Immature Dental Pulp Stem Cells Showed Renotropic and Pericyte-Like Properties in Acute Renal Failure in Rats. AB - Acute renal failure (ARF) is a common renal disease that can lead to high mortality. Recovery from ARF occurs with the replacement of necrotic tubular cells by functional tubular epithelial cells and the normalization of microvascular endothelial cell function in the peritubular capillaries. Conventional therapeutic techniques are often ineffective against ARF. Hence, stem cell therapies, which act through multiple trophic and regenerative mechanisms, are encouraging. We investigated the homing of human immature dental pulp stem cells (IDPSCs) after endovenous (EV) or intraperitoneal (IP) injection, in immunocompetent Wistar rats with ARF induced by intramuscular injection of glycerol, without the use of immunosuppression. The cells, which had been cryopreserved for 6 years, were CD105(+), CD73(+), CD44(+), and partly, STRO-1(+) and CD146(+), and presented unaltered mesoderm differentiation potential. The presence of these cells in the tubular region of the kidney and in the peritubular capillaries was demonstrated. These cells accelerate tubular epithelial cell regeneration through significant increase of Ki-67-immunoreactive cells in damaged kidney. Flow cytometry analysis confirmed that IDPSCs home to the kidneys (EV 34.10% and IP 33.25%); a lower percentage of cells was found in the liver (EV 19.05% and IP 9.10%), in the muscles (EV 6.30% and IP 1.35%), and in the lungs (EV 2.0% and IP 1.85%). After infusion into rat, these cells express pericyte markers, such as CD146(+), STRO-1(+), and vascular endothelial growth factor (VEGF(+)). We found that IDPSCs demonstrate renotropic and pericyte-like properties and contributed to restore renal tubule structure in an experimental rat ARF model. PMID- 26858899 TI - A Rotating Bioreactor for Scalable Culture and Differentiation of Respiratory Epithelium. AB - Respiratory epithelium is difficult to grow in vitro, as it requires a well maintained polarizing air-liquid interface (ALI) to maintain differentiation. Traditional methods rely on permeable membrane culture inserts, which are difficult to work with and are ill-suited for the production of large numbers of cells, such as the quantities required for cell-based clinical therapies. Herein, we investigate an alternative form of culture in which the cells are placed on a porous substrate that is continuously rolled, such that the monolayer of cells is alternately submerged in media or apically exposed to air. Our prototype bioreactor is reliable for up to 21 days of continuous culture and is designed for scale-up for large-scale cell culture with continuous medium and gas exchange. Normal human bronchial epithelial (NHBE) cells were cultured on an absorbent substrate in the reactor for periods of 7, 14, and 21 days and were compared to static controls that were submerged in media. Quantification by immunohistochemistry and quantitative PCR of markers specific to differentiated respiratory epithelium indicated increased cilia, mucous production, and tight junction formation in the rolled cultures, compared to static. Together with scanning electron microscopy and paraffin histology, the data indicate that the intermittent ALI provided by the rolling bioreactor promotes a polarized epithelial phenotype over a period of 21 days. PMID- 26858901 TI - Disease and Stem Cell-Based Analysis of the 2014 ASNTR Meeting. AB - A wide variety of subjects are presented at the annual American Society of Neural Therapy and Repair meeting every year, as typified by this summary of the 2014 meeting. Parkinson's disease-related presentations were again the most popular topic, with traumatic brain injury, spinal cord injury, and stroke being close behind. Other disorders included Huntington's disease, brain cancer, and bipolar disorders. Several studies were related to multiple diseases, and many studies attempted to reveal more about the disease process. The use of scaffolds, drugs, and gene therapy as disease models and/or potential therapies were also featured. An increasing proportion of presentations related to stem cells, with the study of multiple stem cell types being the most common. Induced pluripotent stem cells were increasingly popular, including two presentations each on a muscle-derived dedifferentiated cell type and cells derived from bipolar patients. Other stem cells, including neural stem cells, mesenchymal stem cells, umbilical cord blood cells, and embryonic stem cells, were featured. More than 55% of the stem cell studies involved transplantation, with human-derived cells being the most frequently transplanted, while rats were the most common recipient. Two human autologous studies for spinal cord injury and hypoxia-derived encephalopathy, while a further three allogenic studies for stroke and spinal cord injury, were also featured. This year's meeting highlights the increasing promise of stem cells and other therapies for the treatment of neurodegenerative disorders. PMID- 26858900 TI - A Combination of Low-Intensity Pulsed Ultrasound and Nanohydroxyapatite Concordantly Enhances Osteogenesis of Adipose-Derived Stem Cells From Buccal Fat Pad. AB - The osteogenic induction of adipose-derived stem cells (ADSCs) has been regarded as an important step in bone tissue engineering. In the present study, we focused on the buccal fat pad (BFP) as a source of adipose tissue, since BFPs are encapsulated by adipose tissue and are often coextirpated during oral surgery. Low-intensity pulsed ultrasound (LIPUS) is effective in the treatment of fractures, and nanohydroxyapatite (NHA) is known as a bone substitute material. Here we investigated the synergistic effects of LIPUS and NHA in the osteogenesis of ADSCs. A combination of LIPUS irritation and NHA as a scaffold significantly increased the osteogenic differentiation of ADSCs in vitro, and in our in vivo study in which ADSCs were transplanted into calvarial bone defects of nude mice, the combinational effect greatly enhanced the new bone formation of the margin of the defects. These results demonstrate that synergistic effects of LIPUS and NHA are capable of effectively inducing the differentiation of ADSCs into osteoblasts, and they suggest a novel therapeutic strategy for bone regeneration by the autotransplantation of ADSCs. PMID- 26858902 TI - Creating a Future of Transplantation. PMID- 26858903 TI - Cryopreservation of Adipose-Derived Mesenchymal Stem Cells. AB - Mesenchymal stem cells (MSCs) have the potential to differentiate into cells of mesodermal origin such as osteoblasts, adipocytes, myocytes, and chondrocytes. They possess an immunosuppressive effect, which makes them a viable cell population for the cell-based therapy of treatment-resistant immune diseases. Adipose-derived mesenchymal stem cells (ASCs) have been demonstrated to have the ability to acquire the properties of subcutaneous adipose tissue particularly easily, and cryopreservation is currently performed as a routine method for preserving ASCs to safely acquire large numbers of cells. However, many studies have reported that cellular activity after freezing and thawing may be affected by the solutions used for cryopreservation. Dimethyl sulfoxide (DMSO) is commonly used as a cryopreservation medium as it diffuses into the cell through the plasma membrane and protects the cells from the damage caused by freezing. As substitutes for DMSO or animal-derived serum, cell banker series, polyvinylpyrrolidone (PVP), sericin and maltose, and methyl cellulose (MC) have been investigated for their clinical applications. It is critical to develop a reliable cell cryopreservation protocol for regenerative medicine using MSCs. PMID- 26858904 TI - Choice of Feeders Is Important When First Establishing iPSCs Derived From Primarily Cultured Human Deciduous Tooth Dental Pulp Cells. AB - Feeder cells are generally required to maintain embryonic stem cells (ESCs)/induced pluripotent stem cells (iPSCs). Mouse embryonic fibroblasts (MEFs) isolated from fetuses and STO mouse stromal cell line are the most widely used feeder cells. The aim of this study was to determine which cells are suitable for establishing iPSCs from human deciduous tooth dental pulp cells (HDDPCs). Primary cultures of HDDPCs were cotransfected with three plasmids containing human OCT3/4, SOX2/KLF4, or LMYC/LIN28 and pmaxGFP by using a novel electroporation method, and then cultured in an ESC qualified medium for 15 days. Emerging colonies were reseeded onto mitomycin C-treated MEFs or STO cells. The colonies were serially passaged for up to 26 passages. During this period, colony morphology was assessed to determine whether cells exhibited ESC-like morphology and alkaline phosphatase activity to evaluate the state of cellular reprogramming. HDDPCs maintained on MEFs were successfully reprogrammed into iPSCs, whereas those maintained on STO cells were not. Once established, the iPSCs were maintained on STO cells without loss of pluripotency. Our results indicate that MEFs are better feeder cells than STO cells for establishing iPSCs. Feeder choice is a key factor enabling efficient generation of iPSCs. PMID- 26858905 TI - Islet Culture/Preservation Before Islet Transplantation. AB - Although islet culture prior to transplantation provides flexibility for the evaluation of isolated islets and the pretreatment of patients, it is well known that isolated islets deteriorate rapidly in culture. Human serum albumin (HSA) is used for medium supplementation instead of fetal bovine serum (FBS), which is typically used for islet culture research, to avoid the introduction of xenogeneic materials. However, FBS contains several factors that are beneficial to islet viability and which also neutralize the endogenous pancreatic enzymes or exogenous enzymes left over from the isolation process. Several groups have reported the comparison of cultures at 22 degrees C and 37 degrees C. Recent studies have demonstrated the superiority of 4 degrees C preservation to 22 degrees C and 37 degrees C cultures. We herein review the current research on islet culture/preservation for clinical islet transplantation. PMID- 26858906 TI - Efficient Gene Transduction of Dispersed Islet Cells in Culture Using Fiber Modified Adenoviral Vectors. AB - To establish novel islet-based therapies, our group has recently developed technologies for creating functional neo-islet tissues in the subcutaneous space by transplanting monolithic sheets of dispersed islet cells (islet cell sheets). Improving cellular function and viability are the next important challenges for enhancing the therapeutic effects. This article describes the adenoviral vector mediated gene transduction of dispersed islet cells under culture conditions. Purified pancreatic islets were obtained from Lewis rats and dissociated into single islet cells. Cells were plated onto laminin-5-coated temperature responsive polymer poly(N-isopropylacrylamide)-immobilized plastic dishes. At 0 h, islet cells were infected for 1 h with either conventional type 5 adenoviral vector (Ad-CA-GFP) or fiber-modified adenoviral vector (AdK7-CA-GFP) harboring a polylysine (K7) peptide in the C terminus of the fiber knob. We investigated gene transduction efficiency at 48 h after infection and found that AdK7-CA-GFP yielded higher transduction efficiencies than Ad-CA-GFP at a multiplicity of infection (MOI) of 5 and 10. For AdK7-CA-GFP at MOI = 10, 84.4 +/- 1.5% of islet cells were found to be genetically transduced without marked vector infection related cellular damage as determined by viable cell number and lactate dehydrogenase (LDH) release assay. After AdK7-CA-GFP infection at MOI = 10, cells remained attached and expanded to nearly full confluency, showing that this adenoviral infection protocol is a feasible approach for creating islet cell sheets. We have shown that dispersed and cultured islet cells can be genetically modified efficiently using fiber-modified adenoviral vectors. Therefore, this gene therapy technique could be used for cellular modification or biological assessment of dispersed islet cells. PMID- 26858907 TI - Human Laminin Isotype Coating for Creating Islet Cell Sheets. AB - Our experimental approach toward the development of new islet-based treatment for diabetes mellitus has been the creation of a monolayered islet cell construct (islet cell sheet), followed by its transplantation into a subcutaneous pocket. Previous studies describe rat laminin-5 (chain composition: alpha3, beta3, gamma2) as a suitable extracellular matrix (ECM) for surfaces comprised of a coated temperature-responsive polymer, poly(N-isopropylacrylamide) (PIPAAm). To progress toward the clinical application of this approach, the present study attempted to identify an optimal human ECM as a coating material on PIPAAm surfaces, which allowed islet cells to attach on the surfaces and subsequently to be harvested as a monolithic cell sheet. Dispersed rat islet cells were seeded onto PIPAAm dishes coated with various human laminin isotypes: human laminin (HL) 211, HL-332, HL-411, HL-511, and HL-placenta. Plating efficiency at day 1, the confluency at day 3, and glucose-stimulated insulin secretion test at day 3 were performed. The highest value of plating efficiency was found in the HL-332-PIPAAm group (83.1 +/- 0.7%). The HL-332-PIPAAm group also showed the highest cellular confluency (98.6 +/- 0.5%). Islet cells cultured on the HL-332-PIPAAm surfaces showed a positive response in the glucose-stimulated insulin secretion test. By reducing culture temperature from 37 degrees C to 20 degrees C in the HL-332 PIPAAm group, cells were able to be harvested as a monolithic islet sheet. The present study showed that HL-332 was an optimal human-derived ECM on a PIPAAm coating for preparing islet cell sheets. PMID- 26858908 TI - Spheroid Formation and Evaluation of Hepatic Cells in a Three-Dimensional Culture Device. AB - In drug discovery, it is very important to evaluate liver cells within an organism. Compared to 2D culture methods, the development of 3D culture techniques for liver cells has been successful in maintaining long-term liver functionality with the formation of a hepatic-specific structure. The key to performing drug testing is the establishment of a stable in vitro evaluation system. In this article, we report a Tapered Stencil for Cluster Culture (TASCL) device developed to create liver spheroids in vitro. The TASCL device will be applied as a toxicity evaluation system for drug discovery. The TASCL device was created with an overall size of 10 mm * 10 mm, containing 400 microwells with a top aperture (500 um * 500 um) and a bottom aperture (300 um diameter circular) per microwell. We evaluated the formation, recovery, and size of HepG2 spheroids in the TASCL device. The formation and recovery were both nearly 100%, and the size of the HepG2 spheroids increased with an increase in the initial cell seeding density. There were no significant differences in the sizes of the spheroids among the microwells. In addition, the HepG2 spheroids obtained using the TASCL device were alive and produced albumin. The morphology of the HepG2 spheroids was investigated using FE-SEM. The spheroids in the microwells exhibited perfectly spherical aggregation. In this report, by adjusting the size of the microwells of the TASCL device, uniform HepG2 spheroids were created, and the device facilitated more precise measurements of the liver function per HepG2 spheroid. Our TASCL device will be useful for application as a toxicity evaluation system for drug testing. PMID- 26858909 TI - Fluorescence Quenching of CdSe/ZnS Quantum Dots by Using Black Hole Quencher Molecules Intermediated With Peptide for Biosensing Application. AB - Quantum dots (QDs) have recently been investigated as fluorescent probes for detecting a very small number of biomolecules and live cells; however, the establishment of molecular imaging technology with on-off control of QD fluorescence remains to be established. Here we have achieved the fluorescence off state of QDs with the conjugation of black hole quencher (BHQ) molecules intermediated with peptide by using streptavidin-QDs585 and biotin-pep-BHQ-1. The fluorescence of streptavidin-QDs585 was decreased by the addition of biotin-pep BHQ-1 in a dose-dependent manner. It has been suggested that the decrease in QDs585 fluorescence occurred through a Forster resonance energy transfer (FRET) mechanism from the analysis of fluorescence intensity and lifetime of streptavidin-QDs585 and QDs585-pep-BHQ-1. QDs585 fluorescence could be quenched by more than 60% efficiency in this system. The sequence of intermediate peptide (pep) was GPLGVRGK, which can be cleaved by matrix metalloproteinases (MMPs) produced by cancer cells. QDs585-pep-BHQ-1 is thus expected to detect the MMP production by the recovery of QDs585 fluorescence as a new bioanalytical agent for molecular imaging. PMID- 26858910 TI - Ovine-Based Collagen Matrix Dressing: Next-Generation Collagen Dressing for Wound Care. AB - Significance: Broad-spectrum metalloproteinase (MMP) reduction along with inherent aspects of an extracellular matrix (ECM) dressing can bring about improved wound healing outcomes and shorter treatment duration. Initial reports of clinical effectiveness of a new ovine-based collagen extracellular matrix (CECM) dressing demonstrate benefits in chronic wound healing. Recent Advances: CECM dressings are processed differently than oxidized regenerated cellulose/collagen dressings. CECM dressings consist primarily of collagens I and III arranged as native fibers that retain the three-dimensional architecture present in tissue ECM. As such, ovine-based ECM dressings represent a new generation of collagen dressings capable of impacting a broad spectrum of MMP excess known to be present in chronic wounds. Critical Issues: While MMPs are essential in normal healing, elevated presence of MMPs has been linked to wound failure. Collagen has been shown to reduce levels of MMPs, acting as a sacrificial substrate for excessive proteases in a chronic wound. Preserving collagen dressings in a more native state enhances bioactivity in terms of the ability to affect the chronic wound environment. Clinical observation and assessment may not be sufficient to identify a wound with elevated protease activity that can break down ECM, affect wound fibroblasts, and impair growth factor response. Future Directions: Collagen dressings that target broad-spectrum excessive MMP levels and can be applied early in the course of care may positively impact healing rates in difficult wounds. Next-generation collagen dressings offer broader MMP reduction capacity while providing a provisional dermal matrix or ECM. PMID- 26858911 TI - New Twist on an Old Favorite: Gentian Violet and Methylene Blue Antibacterial Foams. AB - Significance: Absorptive antibacterial dressings that assist in controlling bioburden without risks of cytotoxicity or residual absorption can be effectively used for prolonged periods throughout the wound healing continuum. Recent Advances: Until recently, gentian violet and methylene blue (GV/MB) antibacterial dressings have been commercially available only in polyvinyl alcohol (PVA) foam; polyurethane (PU) foam bonded with GV and MB with thin film backing is now commercially available. GV/MB PU foam does not require hydration or a necessary secondary dressing. GV/MB PVA and PU foam dressings were recently granted FDA clearance as antibacterial dressings, as opposed to bacteriostatic dressings as previously classified. Within the class of antibacterial dressings, GV/MB foam dressings are of lower cost alternative to silver- or iodine-based antibacterial dressings with no risk of absorption of any of the foam components into the tissues. Critical Issues: Control of wound bioburden levels by antibacterial agents and absorption of excess exudate are crucial in preventing infections that drastically increase the price of wound care. Use of GV/MB dressings may improve wound healing outcomes and decrease overall costs through super absorption, promotion of autolytic debridement, bioburden reduction, ease of use, and decreased dressing change frequency. Future Directions: Evolution in resistant bacterial strains will drive continual changes in advanced wound care products. Demand will increase for economically priced, versatile wound care dressings that assist in debridement, maintain a moist wound environment, absorb and trap bacterial debris, and decrease dressing change frequency. PMID- 26858913 TI - Choosing a Wound Dressing Based on Common Wound Characteristics. AB - Significance: Chronic wounds are a major healthcare burden.The practitioner should have an appropriate understanding of both the etiology of the wound as well as the optimal type of dressings to use. Fundamental wound characteristics may be used to guide the practitioner's choice of dressings. The identification of optimal dressings to use for a particular wound type is an important element in facilitating wound healing. Recent Advances: Researchers have sought to design wound dressings that aim to optimize each stage in the healing process. In addition, dressings have been designed to target and kill infection-causing bacteria, with the incorporation of antimicrobial agents. Critical Issues: Chronic wounds are frequently dynamic in presentation, and the numerous wound dressings available make dressing selection challenging for the practitioner. Choosing the correct dressing decreases time to healing, provides cost-effective care, and improves patient quality of life. Future Directions: Research into the mechanisms of wound healing has enhanced our ability to heal chronic wounds at a faster rate through the use of moisture-retentive dressings. Newer dressings are incorporating the use of nanotechnology by incorporating miniature electrical sensors into the dressing. These dressings are engineered to detect changes in a wound environment and alert the patient or practitioner by altering the color of the dressing or sending a message to a smartphone. Additional investigations are underway that incorporate biologic material such as stem cells into dressings. PMID- 26858912 TI - Topical Collagen-Based Biomaterials for Chronic Wounds: Rationale and Clinical Application. AB - Significance: The extracellular matrix (ECM) is known to be deficient in chronic wounds. Collagen is the major protein in the ECM. Many claims are made while extolling the virtues of collagen-based biomaterials in promoting cell growth and modulating matrix metalloproteinases. This review will explore the rationale for using topical collagen or ECM as an interface for healing. Recent Advances: Rapid improvements in electrospinning and nanotechnology have resulted in the creation of third-generation biomaterials that mimic the native ECM, stimulate cellular and genetic responses in the target tissue, and provide a platform for controlled release of bioactive molecules and live cells. Although the major focus is currently on development of artificial tissues and organ regeneration, better understanding of the mechanisms that stimulate wound healing can be applied to specific deficits in the chronic wound. Critical Issues: When choosing between the various advanced wound-care products and dressings, the clinician is challenged to select the most appropriate material at the right time. Understanding how the ECM components promote tissue regeneration and modulate the wound microenvironment will facilitate those choices. Laboratory discoveries of biomolecular and cellular strategies that promote skin regeneration rather than repair should be demonstrated to translate to deficits in the chronic wound. Future Directions: Cost-effective production of materials that utilize non mammalian sources of collagen or ECM components combined with synthetic scaffolding will provide an optimal structure for cellular ingrowth and modulation of the chronic wound microenvironment to facilitate healing. These bioengineered materials will be customizable to provide time-released delivery of bioactive molecules or drugs based on the degradation rate of the scaffold or specific signals from the wound. PMID- 26858915 TI - National Surveys of Population Health: Big Data Analytics for Mobile Health Monitors. AB - At the core of the healthcare crisis is fundamental lack of actionable data. Such data could stratify individuals within populations to predict which persons have which outcomes. If baselines existed for all variations of all conditions, then managing health could be improved by matching the measuring of individuals to their cohort in the population. The scale required for complete baselines involves effective National Surveys of Population Health (NSPH). Traditionally, these have been focused upon acute medicine, measuring people to contain the spread of epidemics. In recent decades, the focus has moved to chronic conditions as well, which require smaller measures over longer times. NSPH have long utilized quality of life questionnaires. Mobile Health Monitors, where computing technologies eliminate manual administration, provide richer data sets for health measurement. Older technologies of telephone interviews will be replaced by newer technologies of smartphone sensors to provide deeper individual measures at more frequent timings across larger-sized populations. Such continuous data can provide personal health records, supporting treatment guidelines specialized for population cohorts. Evidence-based medicine will become feasible by leveraging hundreds of millions of persons carrying mobile devices interacting with Internet scale services for Big Data Analytics. PMID- 26858914 TI - Adiponectin as an anti-fibrotic and anti-inflammatory adipokine in the liver. AB - Hepatic fibrosis is a dynamic process resulting from excessive deposition of extracellular matrix in the liver; uncontrolled progression of fibrosis can eventually lead to liver cirrhosis and/or hepatocellular carcinoma. The fibrogenic process is complex and modulated by a number of both hepatic and extra hepatic biological factors. Growing evidence indicates that adipokines, a group of cytokines produced by adipose tissue, impart dynamic functions in liver and are involved in modulation of hepatic fibrosis. In particular, two key adipokines, adiponectin and leptin, directly regulate many biological responses closely associated with development and progression of hepatic fibrosis. Leptin acts as a pro-fibrogenic cytokine, while adiponectin possesses anti-fibrogenic and anti-inflammatory properties. Adiponectin, acting via its cognate receptors, adiponectin receptors 1 and 2, potently suppresses fibrosis and inflammation in liver via multiple mechanisms. This review summarizes recent findings concerning the role of adiponectin in fibrogenic process in liver and addresses the underlying molecular mechanisms in modulation of fibrosis. PMID- 26858916 TI - A Supervised Learning Process to Validate Online Disease Reports for Use in Predictive Models. AB - Pathogen distribution models that predict spatial variation in disease occurrence require data from a large number of geographic locations to generate disease risk maps. Traditionally, this process has used data from public health reporting systems; however, using online reports of new infections could speed up the process dramatically. Data from both public health systems and online sources must be validated before they can be used, but no mechanisms exist to validate data from online media reports. We have developed a supervised learning process to validate geolocated disease outbreak data in a timely manner. The process uses three input features, the data source and two metrics derived from the location of each disease occurrence. The location of disease occurrence provides information on the probability of disease occurrence at that location based on environmental and socioeconomic factors and the distance within or outside the current known disease extent. The process also uses validation scores, generated by disease experts who review a subset of the data, to build a training data set. The aim of the supervised learning process is to generate validation scores that can be used as weights going into the pathogen distribution model. After analyzing the three input features and testing the performance of alternative processes, we selected a cascade of ensembles comprising logistic regressors. Parameter values for the training data subset size, number of predictors, and number of layers in the cascade were tested before the process was deployed. The final configuration was tested using data for two contrasting diseases (dengue and cholera), and 66%-79% of data points were assigned a validation score. The remaining data points are scored by the experts, and the results inform the training data set for the next set of predictors, as well as going to the pathogen distribution model. The new supervised learning process has been implemented within our live site and is being used to validate the data that our system uses to produce updated predictive disease maps on a weekly basis. PMID- 26858917 TI - Integral Whole Brain Dose from Stereotactic Radiosurgery of 47 Metastatic Lesions: A Dosimetric Case Study. AB - This report describes the case of a 15-year-old male diagnosed with primary ALK positive adenocarcinoma of the lung metastatic to the brain. He was treated with surgical resection for a single lesion followed by whole brain radiotherapy and subsequently underwent 10 courses of stereotactic radiosurgery for 47 lesions delivered over a four-year period. Currently, all metastatic lesions in the brain are completely resolved or locally controlled. PMID- 26858918 TI - Intraosseous Metastasizing of Pineoblastoma into the Anterior Skull Base, Calvarial Bones, and Vertebrae. AB - Pineoblastoma is a rare malignant tumor of the central nervous system (CNS), which arises from the parenchyma of the pineal gland. It is characterized by aggressive clinical behavior and frequent metastases along the craniospinal axis. Extraneural metastases may occur due to surgical seeding of tumor cells beyond the dura and/or hematogenous spread, ventriculoperitoneal shunting, or through Batson's plexus. To our knowledge, only six documented cases of intraosseous metastases of pineoblastoma are described in the literature. A 23-year-old female patient presented with clinical and radiological symptoms of a pineal tumor causing secondary hydrocephalus. After initial surgical treatment, chemotherapy, and local radiotherapy with craniospinal irradiation, she developed multiple metastases affecting the anterior skull base, intracranial meninges, frontal bone, and finally, the entire vertebral column. The patient received surgical treatment for the anterior skull base metastasis, repeated irradiation of the neuraxis, radiosurgical and radiotherapeutic procedures, and chemotherapy. The patient survived 57 months after the primary disease manifestation and died of multiple metastases. This presented case is the first known description of metastasis of pineoblastoma in the anterior cranial base. Multiple intracranial metastases were suppressed using CyberKnife radiation treatment and chemotherapy until massive involvement of spinal column occurred. Interestingly, no signs of brain radiation necrosis after repeated radiation treatments were observed, and the patient developed only moderate neurocognitive decline. PMID- 26858920 TI - Exceptional Clinical Response to BRAF-Targeted Therapy in a Patient with Metastatic Sarcoma. AB - Soft tissue sarcomas (STS) are a rare and heterogeneous group of tumors arising from mesenchymal tissue comprising 1% of all adult cancers. The prognosis of metastatic STS is dismal. As there are few active drugs, there is a critical need to find new therapeutic alternatives in order to improve outcomes. Most sarcoma subtypes are fairly resistant to standard chemotherapy regimens and/or have a short duration of response. The era of molecular targeted therapy may present new treatment options for metastatic STS and an opportunity to drive biomarker discovery and personalized medicine. This case report describes a patient with a synchronous metastatic high-grade sarcoma who was treated with BRAF-targeted therapy with resolution of his metastatic lesions. To our knowledge, this exceptional response has not been described in sarcoma literature. The patient presented with a large anterior abdominopelvic wall mass. Biopsy showed a high grade spindle cell sarcoma. Staging scans confirmed two pulmonary metastases. He was initiated on combination chemotherapy with mixed results. He received 50 Gy of radiation to the primary tumor followed by two additional cycles of combination chemotherapy, with an interval increase in the size of the pulmonary metastases. Molecular testing revealed a BRAF V600E mutation in the primary tumor. The patient was initiated on dabrafenib/trametinib with a dramatic response and resolution of his pulmonary metastases. The patient underwent surgical resection of his primary mass, and pathology confirmed no evidence of residual disease. Detailed genetic characterization of STS coupled with novel therapeutic strategies, including molecular targeted therapy, may have the potential to transform the care of patients diagnosed with sarcoma. PMID- 26858919 TI - A Case of Metastatic Head and Neck Squamous Cell Carcinoma with Multiple Treatments Including Stereotactic Ablative Body Radiotherapy Alone for Oligometastases to the Parotid Gland. AB - Head and neck squamous cell carcinoma (HNSCC) has a reported average of around 15% metastases at presentation with chemotherapy being the mainstay of treatment for widely metastatic disease. However, in select patients with oligometastatic disease, local ablative therapy (commonly including surgery or radiotherapy) can be utilized with the possibility of improving survival, decreasing morbidity from the metastases, and obviating the need for systemic therapy with its possible side effects. However, most research has been of ablative therapy has been performed for pulmonary and hepatic oligometastatic lesions. In this case, we present a patient who initially presented with a metastatic base of tongue malignancy with left axilla metastases who was treated palliatively with systemic therapy with an initial complete response. She subsequently progressed on maintenance therapy with a locoregional recurrence that was treated with definitive chemoradiation with complete response. There was a subsequent recurrence again in the left axilla that was treated as well with chemoradiation with complete response. Next, there was a recurrence in the right occipital lobe and left parotid gland with treatment with surgical resection, plus stereotactic radiotherapy boost and stereotactic ablative body radiotherapy (SABR), respectively. This all occurred over a 30-month time frame from initial therapy to her last treatment, with an additional 42 months at the present time with no recurrence. This case highlights the future of care of oligometastatic disease of HNSCC with potential long-term survival in appropriately selected patients treated with stereotactic ablative body radiotherapy. Furthermore, this is one of the first reported cases in the literature of SABR for an oligometastatic lesion of the parotid gland, especially from squamous cell carcinoma (SCC) of the oral cavity, with no recurrence of disease over 40 months removed from treatment. PMID- 26858921 TI - Lung Cancer in Pregnancy: An Unusual Case of Complete Response to Chemotherapy. AB - The diagnosis of lung cancer in pregnancy is rare. Most cases are quite advanced and have dismal outcomes despite treatment. We present the case of a 26-year-old woman who was diagnosed with Stage IIIA (T3N2M0) squamous-cell carcinoma of the lung with lymphoepithelioma-like features at the 18(th) week of pregnancy. A chest CT revealed a large right hilar mass with obliteration of the right main bronchus and resulting collapse of the right lung with mediastinal shift to the right. A transbronchial biopsy of the mass and a subcarinal lymph node confirmed poorly differentiated squamous cell carcinoma with lymphoepithelioma-like features. Brain MRI, PET, and CT scans were negative for distant metastasis. The patient received four cycles of neoadjuvant cisplatin and docetaxel with a complete radiographic response. She delivered a healthy baby girl at 35 weeks gestation. Post-partum, she received radiation to the right hilum and mediastinum as consolidation. The patient continues to remain free of disease more than 16 months after initial diagnosis. To our knowledge, this is the only reported case of lung cancer in pregnancy where there is a complete response to chemotherapy. The histology is also distinct from other reported cases. In addition, this case exemplifies the relative safety and efficacy of chemotherapy during the later stages of pregnancy. As long as a patient is beyond the first trimester of pregnancy, platinum-based doublet chemotherapy may be considered as a feasible treatment option. PMID- 26858922 TI - A Case of Complete and Durable Molecular Remission of Chronic Lymphocytic Leukemia Following Treatment with Epigallocatechin-3-gallate, an Extract of Green Tea. AB - We report the case of a 48-year-old man who achieved a complete molecular remission 20 years after a diagnosis of chronic lymphocytic leukemia while using epigallicatechin-3-gallate, an extract of green tea. The patient presented at age 28 with lymphocytosis, mild anemia, mild thrombocytopenia, and massive splenomegaly, for which a splenectomy was performed. He was then followed expectantly. Over the next two decades, he suffered two symptomatic chronic lymphocytic leukemia-related events. The first occurred twelve years after diagnosis (at age 40) when the patient developed fevers, night sweats, and moderate anemia. He was diagnosed with autoimmune hemolytic anemia secondary to chronic lymphocytic leukemia. The patient declined conventional therapy in favor of a diet, exercise, and supplement regimen, and recovered from the autoimmune hemolytic anemia though the underlying chronic lymphocytic leukemia remained evident. This is the first published case report of "spontaneous" recovery from secondary autoimmune hemolytic anemia in an adult. Over the second decade following chronic lymphocytic leukemia diagnosis, serial bone marrow biopsies demonstrated increasing lymphocytosis, with minimal peripheral lymphocytosis. However, twenty years after diagnosis, peripheral lymphocytosis accelerated, with white blood cell counts rising to 55,000/uL. Because the patient continued to refuse conventional therapy, he was treated instead with a supplement regimen that included high doses of epigallocatechin-3-gallate, a green tea extract. Peripheral lymphocytosis resolved. More remarkably, a bone marrow examination, including flow cytometry, showed no evidence of a malignant clone. Two years later (at age 51), the peripheral blood and bone marrow were without molecular evidence of chronic lymphocytic leukemia or any malignancy. The patient remains well at age 52. PMID- 26858923 TI - Hypocalcemia in Malignancy - Unexpected but Common. AB - One of the most common metabolic abnormalities found in patients with malignancy is hypercalcemia. Hypocalcemia is a rare occurrence and is often found to be associated with renal failure and patients taking bisphosphonate therapy for bone metastasis in this patient population. Here, we present two different case reports with hypocalcemia. A 66-year-old female with a recent diagnosis of tonsillar diffuse B-cell lymphoma admitted with complaints of generalized weakness after one cycle of R-CHOP, found to have neutropenia, a low calcium level, high PTH, and low 25-hydroxy Vitamin D levels. She was given calcium gluconate and supplemental 25-hydroxy Vitamin D. On day 2, the patient's symptoms and counts improved. The second patient was a 64-year-old male with recurrent metastatic laryngeal carcinoma, along with a second locally advanced primary rectal adenocarcinoma, presented with severe hypocalcemia and a low PTH level. The patient was on adjuvant chemotherapy and exhibited Chvostek's sign, along with perioral numbness, tingling, and twitching sensations, which eventually led to dysphagia. He was treated with calcium gluconate, calcitriol, and calcium carbonate. Signs and symptoms, along with lab values, improved on day 4. These cases suggest that calcium kinetics and 25-hydroxy Vitamin D levels need to be monitored in these patient populations in a routine manner. PMID- 26858924 TI - Merkel Cell Carcinoma: When Does Size Matter for Radiotherapy? AB - Merkel cell carcinoma is a very aggressive, rare cancer of the skin. It has a high propensity for local, regional, and distant recurrence and has recently been associated with a viral etiology from the recently diagnosed Merkel Cell Polyoma Virus. The optimal management remains controversial. We discuss the case of a man with a 26 cm axillary lymph node metastasis of unknown primary treated with radiotherapy. PMID- 26858925 TI - Continuous intake of resistant maltodextrin enhanced intestinal immune response through changes in the intestinal environment in mice. AB - We investigated the effect of resistant maltodextrin (RMD), a non-viscous soluble dietary fiber, on intestinal immune response and its mechanism in mice. Intestinal and fecal immunoglobulin A (IgA) were determined as indicators of intestinal immune response, and changes in the intestinal environment were focused to study the mechanism. BALB/c mice were fed one of three experimental diets, a control diet or a diet containing either 5% or 7.5% RMD, for two weeks. Continuous intake of RMD dose-dependently increased total IgA levels in the intestinal tract. Total IgA production from the cecal mucosa was significantly increased by RMD intake, while there were no significant differences in mucosal IgA production between the control group and experimental groups in the small intestine and colon. Continuous intake of RMD changed the composition of the cecal contents; that is, the composition of the cecal microbiota was changed, and short-chain fatty acids (SCFAs) were increased. There was an increased trend in Bacteroidales in the cecal microbiota, and butyrate, an SCFA, was significantly increased. Our study demonstrated that continuous intake of RMD enhanced the intestinal immune response by increasing the production of IgA in the intestinal tract. It suggested that the increase in total SCFAs and changes in the intestinal microbiota resulting from the fermentation of RMD orally ingested were associated with the induction of IgA production in intestinal immune cells, with the IgA production of the cecal mucosa in particular being significantly increased. PMID- 26858926 TI - Intake of a fermented soymilk beverage containing moderate levels of isoflavone aglycones enhances bioavailability of isoflavones in healthy premenopausal Japanese women: a double-blind, placebo-controlled, single-dose, crossover trial. AB - This study aimed to investigate the bioavailability of serum isoflavones after the intake of soymilk fermented by Lactobacillus casei strain Shirota containing 32.5% isoflavone aglycones (FSM) or placebo soymilk containing no isoflavone aglycones (SM). In a double-blind, placebo-controlled, single-dose, crossover trial, 7 healthy premenopausal Japanese women (mean age: 35.3 +/- 11.0) consumed FSM or SM on day 1 and crossed over to the other soymilk after a 6-day washout period. Serum isoflavones in blood samples collected at 0, 1, 2, 3, 4, and 5 hr after intake were analyzed by liquid chromatography coupled with tandem mass spectrometry. The area under the curve (AUC) values for the serum concentrations of genistein and total isoflavones were significantly higher, by about 1.4-fold, up to 5 hr after FSM intake compared with SM intake (each p<0.05), and that of daidzein tended to be higher after FSM intake. In addition, AUC analysis of total isoflavones for individual subjects revealed that 5 out of 7 subjects had higher AUC values after FSM intake compared with SM intake and that the 2 remaining subjects had similar AUC values. These 2 subjects had higher AUC values after SM intake (mean, 2,502 +/- 348) than those of the other subjects (mean, 1,158 +/- 269). These results indicate that the bioavailability of isoflavones, especially genistein, is enhanced after the intake of FSM containing 32.5% isoflavone aglycones compared with intake of SM containing no isoflavone aglycones and that the enhancement is observed in healthy premenopausal Japanese women whose isoflavone absorption capacity is low after SM intake. PMID- 26858927 TI - Adhesion properties of a putative polymorphic fimbrial subunit protein from Bifidobacterium longum subsp. longum. AB - In our previous study, we found that the open reading frame bl0675 in the genome of Bifidobacterium longum subsp. longum isolated from human feces encoded a novel putative fimbrial protein, was highly polymorphic, and had five variants (A, B, C, D, and E types). The aim of this study was to evaluate the affinity of these variants to porcine colonic mucins (PCMs). Protein-binding properties were examined using the recombinant BL0675 protein containing a C-terminal 6 * His tag (His-BL0675). Surface plasmon resonance analysis demonstrated that the His-BL0675 A type had strong affinity to PCMs (KD = 9.82 * 10(-8) M), whereas the B, C, D, and E types exhibited little or no binding. In a competitive enzyme-linked immunosorbent assay, His-BL0675 A type binding was reduced by addition of mucin oligosaccharides, suggesting that the binding occurs via carbohydrate chains of PCMs. The localization of BL0675 to the B. longum subsp. longum cell surface was confirmed by western blot analysis using A type polyclonal antibodies. Bacterial adhesion of B. longum subsp. longum to PCMs was also blocked by A type-specific antibodies; however, its adhesion properties were strain specific. Our results suggest that the BL0675 variants significantly contribute to the adhesion of B. longum subsp. longum strains. The expression and the adhesive properties of this protein are affected by genetic polymorphisms and are specific for B. longum subsp. longum strains. However, further studies are required on the properties of binding of these putative fimbrial proteins to the human gastrointestinal tract. PMID- 26858928 TI - Beneficial effects of citrus juice fermented with Lactobacillus plantarum YIT 0132 on atopic dermatitis: results of daily intake by adult patients in two open trials. AB - This study aimed to examine whether daily intake of citrus juice containing heat killed Lactobacillus plantarum YIT 0132 (LP0132-fermented juice) alleviates symptoms of atopic dermatitis. This was a natural extension of our previous study in which LP0132 was shown to enhance IL-10 production in vitro and LP0132 fermented juice was found to alleviate symptoms and enhance quality of life (QOL) in patients with Japanese cedar pollinosis. In two open trials, Trial 1 and Trial 2, 32 and 18 adult patients with mild to moderate atopic dermatitis consumed LP0132-fermented juice for 8 weeks. Skin conditions and QOL were subjectively evaluated using Skindex-16 before intake of the juice (Pre-treatment), 8 weeks after starting intake (Treatment) and 8 weeks after termination of intake (Post treatment). Blood parameters were also analyzed. Comparison of the Treatment and Post-treatment time points with the Pre-treatment time point revealed significant reductions in the Skindex-16 overall score and the 3 domain subscores (symptoms, emotions, and functioning domains) in both trials. Moreover, blood levels of eosinophil cationic protein (ECP), total immunoglobulin E (IgE) and specific IgEs for Japanese cedar and cypress pollen were significantly attenuated in Trial 2. The findings suggest that daily intake of citrus fermented juice containing heat killed LP0132 has beneficial effects on symptoms and QOL in patients with mild to moderate atopic dermatitis due to an immunomodulatory effect via attenuation of IgE and ECP. PMID- 26858929 TI - Effects of prebiotic oligosaccharides consumption on the growth and expression profile of cell surface-associated proteins of a potential probiotic Lactobacillus rhamnosus FSMM15. AB - To investigate carbohydrate preference of a potential probiotic, Lactobacillus rhamnosus FSMM15, six prebiotics, including two milk-derived prebiotics, galactooligosaccharides and lacto-N-biose I, and four plant-origin prebiotics, beet oligosaccharide syrup, difructose anhydride III, fructooligosaccharides, and raffinose, were examined. The strain utilized the milk-derived prebiotics at similar levels to glucose but did not utilize the plant-origin ones in the same manner, reflecting their genetic background, which allows them to adapt to dairy ecological niches. These prebiotics had little influence on the expression pattern of cell surface-associated proteins in the strain; however, an ATP binding cassette transporter substrate-binding protein and a glyceraldehyde-3 phosphate dehydrogenase were suggested to be upregulated in response to carbon starvation stress. PMID- 26858930 TI - Comparison of activity to stimulate mucosal IgA production between Leuconostoc mesenteroides strain NTM048 and type strain JCM6124 in mice. AB - The effects of Leuconostoc mesenteroides strain NTM048 and type strain JCM6124(T) on the murine immune system were characterized. Although the bacterial cells and exopolysaccharides of each strain induced immunoglobulin A production in Peyer's patch cells, the effects of NTM048 were more potent than those of JCM6124(T). Oral administration of the cells of each strain increased the fecal immunoglobulin A content in NTM048-treated mice, but not in JCM6124(T)-treated mice. A flow cytometric analysis showed that the CD4(+) T-cell populations in the mouse spleens tended to increase in the NTM048 group. These results suggest that immunomodulating ability is characteristic of strain NTM048. PMID- 26858931 TI - Fever and multilobular mass of the right lung in a young adult with asthma. AB - We report a case of a 37-year-old mild asthmatic male presenting with fever, productive cough and chest pain. The chest x-ray showed a multilobular perihilar shadow of the right lung with a mass-like appearance, confirmed by the CT-scan. He was diagnosed with allergic bronchopulmonary aspergillosis (ABPA). ABPA usually manifests as chronic asthma, recurrent pulmonary infiltrates and bronchiectasis. However, it can rarely be seen in patients with mild asthma and with an unusual radiological presentation of a solid mass. PMID- 26858932 TI - Aggressive cutaneous zygomycosis caused by Apophysomyces variabilis in an immunocompetent child. AB - A zygomycetous fungus was observed in a biopsy of a 9-year-old male. The patient was presented with severe cutaneous lesions subsequent to a traumatic car accident. Following fungal detection, antifungal treatment was prescribed but condition deteriorated rapidly and above knee amputation was done as lifesaving and to control fungal infection. Analysis of the 28 S rRNA gene (accession KT149770) aligned the isolate with members of the genus Apophysomyces and the pathogen was identified as Apophysomces variabilis. PMID- 26858933 TI - Optimizing Cancer Care Delivery through Implementation Science. AB - The 2013 Institute of Medicine report investigating cancer care concluded that the cancer care delivery system is in crisis due to an increased demand for care, increasing complexity of treatment, decreasing work force, and rising costs. Engaging patients and incorporating evidence-based care into routine clinical practice are essential components of a high-quality cancer delivery system. However, a gap currently exists between the identification of beneficial research findings and the application in clinical practice. Implementation research strives to address this gap. In this review, we discuss key components of high quality implementation research. We then apply these concepts to a current cancer care delivery challenge in women's health, specifically the implementation of a surgery decision aid for women newly diagnosed with breast cancer. PMID- 26858934 TI - Cancer Care Delivery and Women's Health: The Role of Patient Navigation. AB - BACKGROUND: Patient navigation (PN) is a patient-centered health-care service delivery model that assists individuals, particularly the medically underserved, in overcoming barriers (e.g., personal, logistical, and system) to care across the cancer care continuum. In 2012, the American College of Surgeons Commission on Cancer (CoC) announced that health-care facilities seeking CoC-accreditation must have PN processes in place starting January 1, 2015. The CoC mandate, in light of the recent findings from centers within the Patient Navigation Research Program and the influx of PN interventions, warrants the present literature review. METHODS: PubMed and Medline were searched for studies published from January 2010 to October 2015, particularly those recent articles within the past 2 years, addressing PN for breast and gynecological cancers, and written in English. Search terms included patient navigation, navigation, navigator, cancer screening, clinical trials, cancer patient, cancer survivor, breast cancer, gynecological cancer, ovarian cancer, uterine cancer, vaginal cancer, and vulvar cancer. RESULTS: Consistent with prior reviews, PN was shown to be effective in helping women who receive cancer screenings, receive more timely diagnostic resolution after a breast and cervical cancer screening abnormality, initiate treatment sooner, receive proper treatment, and improve quality of life after cancer diagnosis. However, several limitations were observed. The majority of PN interventions focused on cancer screening and diagnostic resolution for breast cancer. As observed in prior reviews, methodological rigor (e.g., randomized controlled trial design) was lacking. CONCLUSION: Future research opportunities include testing PN interventions in the post-treatment settings and among gynecological cancer patient populations, age-related barriers to effective PN, and collaborative efforts between community health workers and patient navigators as care goes across segments of the cancer control continuum. As PN programs continue to develop and become a standard of care, further research will be required to determine the effectiveness of cancer PN across the cancer care continuum, and in different patient populations. PMID- 26858935 TI - Clinical Overview of MDM2/X-Targeted Therapies. AB - MDM2 and MDMX are the primary negative regulators of p53, which under normal conditions maintain low intracellular levels of p53 by targeting it to the proteasome for rapid degradation and inhibiting its transcriptional activity. Both MDM2 and MDMX function as powerful oncogenes and are commonly over-expressed in some cancers, including sarcoma (~20%) and breast cancer (~15%). In contrast to tumors that are p53 mutant, whereby the current therapeutic strategy restores the normal active conformation of p53, MDM2 and MDMX represent logical therapeutic targets in cancer for increasing wild-type (WT) p53 expression and activities. Recent preclinical studies suggest that there may also be situations that MDM2/X inhibitors could be used in p53 mutant tumors. Since the discovery of nutlin-3a, the first in a class of small molecule MDM2 inhibitors that binds to the hydrophobic cleft in the N-terminus of MDM2, preventing its association with p53, there is now an extensive list of related compounds. In addition, a new class of stapled peptides that can target both MDM2 and MDMX have also been developed. Importantly, preclinical modeling, which has demonstrated effective in vitro and in vivo killing of WT p53 cancer cells, has now been translated into early clinical trials allowing better assessment of their biological effects and toxicities in patients. In this overview, we will review the current MDM2- and MDMX-targeted therapies in development, focusing particularly on compounds that have entered into early phase clinical trials. We will highlight the challenges pertaining to predictive biomarkers for and toxicities associated with these compounds, as well as identify potential combinatorial strategies to enhance its anti-cancer efficacy. PMID- 26858936 TI - Protons, Photons, and the Prostate - Is There Emerging Evidence in the Ongoing Discussion on Particle Therapy for the Treatment of Prostate Cancer? AB - Proton therapy is actively and repeatedly discussed within the framework of particle therapy for the treatment of prostate cancer (PC). The argument in favor of treating the prostate with protons is partly financial: given that small volumes are treated, treatment times are low, resulting in a hypothetical high patient throughput. However, such considerations should not form the basis of medical decision-making. There are also physical and biological arguments which further support the use of particle therapy for PC. The only relevant randomized data currently available is the study by Zietman and colleagues, comparing a high to a low proton boost, resulting in a significant increase in PSA-free survival in the experimental (high dose) arm (1). With modern photon treatments and image guided radiotherapy (IGRT), equally high doses can be applied with photons and, thus, a randomized trial comparing high-end photons to protons is warranted. For high-linear energy transfer (LET) particles, such as carbon ions, the increase in relative biological effectiveness could potentially convert into an improvement in outcome. Additionally, through the physical differences of protons and carbon ions, the steeper dose gradient with carbon ions and the lack of beam broadening in the carbon beam lead to a superior dose distribution supporting the idea of hypofractionation. Biological and clinical data are emerging, however, has practice-changing evidence already arrived? PMID- 26858937 TI - Assessment of Geant4 Prompt-Gamma Emission Yields in the Context of Proton Therapy Monitoring. AB - Monte Carlo tools have been long used to assist the research and development of solutions for proton therapy monitoring. The present work focuses on the prompt gamma emission yields by comparing experimental data with the outcomes of the current version of Geant4 using all applicable proton inelastic models. For the case in study and using the binary cascade model, it was found that Geant4 overestimates the prompt-gamma emission yields by 40.2 +/- 0.3%, even though it predicts the prompt-gamma profile length of the experimental profile accurately. In addition, the default implementations of all proton inelastic models show an overestimation in the number of prompt gammas emitted. Finally, a set of built-in options and physically sound Geant4 source code changes have been tested in order to try to improve the discrepancy observed. A satisfactory agreement was found when using the QMD model with a wave packet width equal to 1.3 fm(2). PMID- 26858938 TI - Mutant p53 Drives Cancer by Subverting Multiple Tumor Suppression Pathways. AB - The tumor suppressor p53 normally acts as a brake to halt damaged cells from perpetrating their genetic errors into future generations. If p53 is disrupted by mutation, it may not only lose these corrective powers, but counterproductively acquire new capacities that drive cancer. A newly emerging manner in which mutant p53 executes its cancer promoting functions is by harnessing key proteins, which normally partner with its wild type, tumor-inhibiting counterpart. In association with the subverted activities of these protein partners, mutant p53 is empowered to act across multiple fundamental cellular pathways (regulating cell division and metabolism) and corrupt them to become cancer promoting. PMID- 26858939 TI - Genetics and Epigenetics of Glioblastoma: Applications and Overall Incidence of IDH1 Mutation. AB - Glioblastoma is the most fatal brain cancer found in humans. Patients suffering from glioblastoma have a dismal prognosis, with a median survival of 15 months. The tumor may develop rapidly de novo in older patients or through progression from anaplastic astrocytomas in younger patients if glioblastoma is primary or secondary, respectively. During the past decade, significant advances have been made in the understanding of processes leading to glioblastoma, and several important genetic defects that appear to be important for the development and progression of this tumor have been identified. Particularly, the discovery of recurrent mutations in the isocitrate dehydrogenase 1 (IDH1) gene has shed new light on the molecular landscape in glioblastoma. Indeed, emerging research on the consequences of mutant IDH1 protein expression suggests that its neomorphic enzymatic activity catalyzing the production of the oncometabolite 2 hydroxyglutarate influences a range of cellular programs that affect the epigenome and contribute to glioblastoma development. One of the exciting observations is the presence of IDH1 mutation in the vast majority of secondary glioblastoma, while it is almost absent in primary glioblastoma. Growing data indicate that this particular mutation has clinical and prognostic importance and will become a critical early distinction in diagnosis of glioblastoma. PMID- 26858940 TI - Impact of Freezing Delay Time on Tissue Samples for Metabolomic Studies. AB - INTRODUCTION: Metabolic profiling of intact tumor tissue by high-resolution magic angle spinning (HR MAS) MR spectroscopy (MRS) provides important biological information possibly useful for clinical diagnosis and development of novel treatment strategies. However, generation of high-quality data requires that sample handling from surgical resection until analysis is performed using systematically validated procedures. In this study, we investigated the effect of postsurgical freezing delay time on global metabolic profiles and stability of individual metabolites in intact tumor tissue. MATERIALS AND METHODS: Tumor tissue samples collected from two patient-derived breast cancer xenograft models (n = 3 for each model) were divided into pieces that were snap-frozen in liquid nitrogen at 0, 15, 30, 60, 90, and 120 min after surgical removal. In addition, one sample was analyzed immediately, representing the metabolic profile of fresh tissue exposed neither to liquid nitrogen nor to room temperature. We also evaluated the metabolic effect of prolonged spinning during the HR MAS experiments in biopsies from breast cancer patients (n = 14). All samples were analyzed by proton HR MAS MRS on a Bruker Avance DRX600 spectrometer, and changes in metabolic profiles were evaluated using multivariate analysis and linear mixed modeling. RESULTS: Multivariate analysis showed that the metabolic differences between the two breast cancer models were more prominent than variation caused by freezing delay time. No significant changes in levels of individual metabolites were observed in samples frozen within 30 min of resection. After this time point, levels of choline increased, whereas ascorbate, creatine, and glutathione (GS) levels decreased. Freezing had a significant effect on several metabolites but is an essential procedure for research and biobank purposes. Furthermore, four metabolites (glucose, glycine, glycerophosphocholine, and choline) were affected by prolonged HR MAS experiment time possibly caused by physical release of metabolites caused by spinning or due to structural degradation processes. CONCLUSION: The MR metabolic profiles of tumor samples are reproducible and robust to variation in postsurgical freezing delay up to 30 min. PMID- 26858943 TI - Emerging perspectives in prostate cancer: Insights from the 4th Asia Pacific Prostate Cancer Conference. PMID- 26858941 TI - Riboregulators: Fine-Tuning Virulence in Shigella. AB - Within the past several years, RNA-mediated regulation (ribo-regulation) has become increasingly recognized for its importance in controlling critical bacterial processes. Regulatory RNA molecules, or riboregulators, are perpetually responsive to changes within the micro-environment of a bacterium. Notably, several characterized riboregulators control virulence in pathogenic bacteria, as is the case for each riboregulator characterized to date in Shigella. The timing of virulence gene expression and the ability of the pathogen to adapt to rapidly changing environmental conditions is critical to the establishment and progression of infection by Shigella species; ribo-regulators mediate each of these important processes. This mini review will present the current state of knowledge regarding RNA-mediated regulation in Shigella by detailing the characterization and function of each identified riboregulator in these pathogens. PMID- 26858942 TI - Evaluation of Immunogenicity and Protective Efficacy Elicited by Mycobacterium bovis BCG Overexpressing Ag85A Protein against Mycobacterium tuberculosis Aerosol Infection. AB - Mycobacterium bovis bacillus Calmette-Guerin (BCG) is currently the only vaccine available for preventing tuberculosis (TB), however, BCG has varying success in preventing pulmonary TB. In this study, a recombinant BCG (rBCG::Ag85A) strain overexpressing the immunodominant Ag85A antigen was constructed, and its immunogenicity and protective efficacy were evaluated. Our results indicated that the Ag85A protein was successfully overexpressed in rBCG::Ag85A, and the Ag85A peptide-MHC complexes on draining lymph node dendritic cells of C57BL/6 mice infected with rBCG::Ag85A were detectable 4 h post-infection. The C57BL/6 mice infected with this strain had stronger antigen-specific interferon-gamma (IFN gamma) responses and higher antibody titers than those immunized with BCG, and the protective experiments showed that rBCG::Ag85A can enhance protection against Mycobacterium tuberculosis (M. tuberculosis) H37Rv infection compared to the BCG vaccine alone. Our results demonstrate the potential of rBCG::Ag85A as a candidate vaccine against TB. PMID- 26858944 TI - Measuring the Mental Health-Care System Responsiveness: Results of an Outpatient Survey in Tehran. AB - As explained by the World Health Organization (WHO) in 2000, the concept of health system responsiveness is one of the core goals of health systems. Since 2000, further efforts have been made to measure health system responsiveness and the factors affecting responsiveness, yet few studies have applied responsiveness concepts to the evaluation of mental health systems. The present study aims to measure responsiveness and its related domains in the mental health-care system of Tehran. Utilizing the same method used by the WHO for its responsiveness survey, responsiveness for outpatient mental health care was evaluated using a validated Farsi questionnaire. A sample of 500 public mental health service users in Tehran participated and subsequently completed the questionnaire. On average, 47% of participants reported experiencing poor responsiveness. Among responsiveness domains, confidentiality and dignity were the best performing factors while autonomy, access to care, and quality of basic amenities were the worst performing. Respondents who reported their social status as low were more likely to experience poor responsiveness overall. Attention and access to care were responsiveness dimensions that performed poorly but were considered to be highly important by study participants. In summary, the study suggests that measuring responsiveness could provide guidance for further development of mental health-care systems to become more patient orientated and provide patients with more respect. PMID- 26858945 TI - Assessment of CEPH-Accredited Institutions Offering Public Health Programs in the United States: A Short Report. AB - AIMS: Examine the distribution of the Council of Education in Public Health (CEPH)-accredited institutions offering public health educational programs in the United States, and characterize their various attributes. METHODS: A search was conducted during the period of June 2014, using the Association of Schools and Programs of Public Health database (ASPPH), and individual university websites to obtain a complete list of CEPH-accredited institutions offering programs in public health at the Certificate, Masters, and Doctoral levels in the United States. Detailed information were abstracted from the various programs offerings, including school/program information, school type, geographic location, admission cycle, education delivery format, public health concentration, number of credits, presence of a global component, joint programs, and tuition. These data were analyzed in August 2014. RESULTS: A total of 85 CEPH-accredited institutions designated as either "Schools of Public Health" or individual "Programs of Public Health" were present in the ASPPH database at the time of this data collection (2014). These institutions offer programs in public health at the Certificate (61%, n = 52), Masters (100%, n = 85), and Doctoral (44%, n = 37) levels in the United States. More than half of the programs offered were provided by schools of public health (58%, n = 49), which were mostly public universities (75%, n = 64), concentrated in the Northeast (22%, n = 19) and mainly admitted students during the fall semester. Ninety-three concentrations of public health currently exist, of which 25 concentrations are predominant. CONCLUSION: To the best of our knowledge, this is the first study that examines the distribution of existing CEPH-accredited public health educational programs offered by United States institutions. We suggest future areas of research to assess existing public health workforce demands, and map them to the curriculums and competencies provided by institutions offering public health educational programs in the United States. This could provide valuable insight on the extent to which public health curriculums are meeting workforce demands. PMID- 26858946 TI - The Healthier the Tastier? USA-India Comparison Studies on Consumer Perception of a Nutritious Agricultural Product at Different Food Processing Levels. AB - Present research compares food beliefs associated with a naturally nutritious agricultural product (namely pulses) in Western and Eastern cultures (namely the US and India). Specifically, this paper focuses on the perception of healthiness and tastefulness of the food and their relationship. Two studies tested the effect of processing level, cultural differences, and branding strategies. In contrast to the well-established inverse relationship between healthiness and tastefulness beliefs observed in the West with industrial food products, the results of both studies revealed a positive association between health and taste for pulses in both West and East. Study 1 shows that this positive association is stronger with lower processing, suggesting the role of naturalness as bridge between health and taste. Focusing on cultural differences, results show that while both West and East hold positive association of health and taste for pulses, this association is stronger for East. However, the role of processing level is significantly stronger in West. Study 2 looks at branding strategies for pulse products with different processing levels in West and East. Results confirm the findings of study 1 on positive association of taste and healthiness and cross-cultural differences. Moreover, study 2 shows that cultural difference between West and East changes the effect of branding strategies on food-related belief and attitude toward food. For American consumers, a future-oriented branding is associated with an enhanced positive healthiness-taste association, whereas a brand image emphasizing tradition leads to increased perception of the taste of product but not necessarily on the healthiness. Current paper has theoretical and practical implications in public policy, health, and marketing. PMID- 26858947 TI - Metabolic Interplay between Peroxisomes and Other Subcellular Organelles Including Mitochondria and the Endoplasmic Reticulum. AB - Peroxisomes are unique subcellular organelles which play an indispensable role in several key metabolic pathways which include: (1.) etherphospholipid biosynthesis; (2.) fatty acid beta-oxidation; (3.) bile acid synthesis; (4.) docosahexaenoic acid (DHA) synthesis; (5.) fatty acid alpha-oxidation; (6.) glyoxylate metabolism; (7.) amino acid degradation, and (8.) ROS/RNS metabolism. The importance of peroxisomes for human health and development is exemplified by the existence of a large number of inborn errors of peroxisome metabolism in which there is an impairment in one or more of the metabolic functions of peroxisomes. Although the clinical signs and symptoms of affected patients differ depending upon the enzyme which is deficient and the extent of the deficiency, the disorders involved are usually (very) severe diseases with neurological dysfunction and early death in many of them. With respect to the role of peroxisomes in metabolism it is clear that peroxisomes are dependent on the functional interplay with other subcellular organelles to sustain their role in metabolism. Indeed, whereas mitochondria can oxidize fatty acids all the way to CO2 and H2O, peroxisomes are only able to chain-shorten fatty acids and the end products of peroxisomal beta-oxidation need to be shuttled to mitochondria for full oxidation to CO2 and H2O. Furthermore, NADH is generated during beta oxidation in peroxisomes and beta-oxidation can only continue if peroxisomes are equipped with a mechanism to reoxidize NADH back to NAD(+), which is now known to be mediated by specific NAD(H)-redox shuttles. In this paper we describe the current state of knowledge about the functional interplay between peroxisomes and other subcellular compartments notably the mitochondria and endoplasmic reticulum for each of the metabolic pathways in which peroxisomes are involved. PMID- 26858948 TI - GRASP: A Multitasking Tether. AB - Originally identified as Golgi stacking factors in vitro, the Golgi reassembly stacking protein (GRASP) family has been shown to act as membrane tethers with multiple cellular roles. As an update to previous comprehensive reviews of the GRASP family (Giuliani et al., 2011; Vinke et al., 2011; Jarvela and Linstedt, 2012), we outline here the latest findings concerning their diverse roles. New insights into the mechanics of GRASP-mediated tethering come from recent crystal structures. The models of how GRASP65 and GRASP55 tether membranes relate directly to their role in Golgi ribbon formation in mammalian cells and the unlinking of the ribbon at the onset of mitosis. However, it is also clear that GRASPs act outside the Golgi with roles at the ER and ER exit sites (ERES). Furthermore, the proteins of this family display other roles upon cellular stress, especially in mediating unconventional secretion of both transmembrane proteins (Golgi bypass) and cytoplasmic proteins (through secretory autophagosomes). PMID- 26858949 TI - Sphingolipids and Epoxidized Lipid Metabolites in the Control of Gut Immunosurveillance and Allergy. AB - The intestinal immune system ingeniously balances the distinct responses of elimination and tolerance of non-self-substances for the creation and maintenance of homeostatic environments. Accumulating evidence has recently shown that various lipids, including dietary one, are involved in the regulation of intestinal immunity and are associated with biophylaxis and immune disorders. Recent advances in the lipidomics allow the identification of novel pathways of lipid metabolism and lipid metabolites for the control of intestinal immunity. In this paper, we describe the effects and functions of lipids, especially sphingolipids and new lipid metabolites originated from dietary oil on the immunomodulation and on the development and pathogenesis of allergic diseases in the intestine. PMID- 26858950 TI - Chondrogenesis of Human Infrapatellar Fat Pad Stem Cells on Acellular Dermal Matrix. AB - Acellular dermal matrix (ADM) has been in clinical use for decades in numerous surgical applications. The ability for ADM to promote cellular repopulation, revascularisation and tissue regeneration is well documented. Adipose stem cells have the ability to differentiate into mesenchymal tissue types, including bone and cartilage. The aim of this study was to investigate the potential interaction between ADM and adipose stem cells in vitro using TGFbeta3 and BMP6. Human infrapatellar fat pad-derived adipose stem cells (IPFP-ASC) were cultured with ADM derived from rat dermis in chondrogenic (TGFbeta3 and BMP6) medium in vitro for 2 and 4 weeks. Histology, qPCR, and immunohistochemistry were performed to assess for markers of chondrogenesis (collagen Type II, SOX9 and proteoglycans). At 4 weeks, cell-scaffold constructs displayed cellular changes consistent with chondrogenesis, with evidence of stratification of cell layers and development of a hyaline-like cartilage layer superficially, which stained positively for collagen Type II and proteoglycans. Significant cell-matrix interaction was seen between the cartilage layer and the ADM itself with seamless integration between each layer. Real time qPCR showed significantly increased COL2A1, SOX9, and ACAN gene expression over 4 weeks when compared to control. COL1A2 gene expression remained unchanged over 4 weeks. We believe that the principles that make ADM versatile and successful for tissue regeneration are applicable to cartilage regeneration. This study demonstrates in vitro the ability for IPFP-ASCs to undergo chondrogenesis, infiltrate, and interact with ADM. These outcomes serve as a platform for in vivo modelling of ADM for cartilage repair. PMID- 26858951 TI - Breast Cancer Genetic Counseling: A Surgeon's Perspective. AB - As surgeons who care for patients with breast cancer, the possibility of a cancer diagnosis being related to a hereditary predisposition is always a consideration. Not only are we as surgeons always trying to identify these patients and families but also we are often asked about a potential hereditary component by the patients and their family members. It is therefore critical that we accurately assess patients to determine who may benefit from genetic testing. Importantly, the potential benefit for identifying a hereditary breast cancer extends beyond the patient to other family members and the risk may not be only for the development of breast cancers, but for other cancers as well. This review was written from the perspective of a surgeon with additional training in cancer genetics in an effort to provide a unique perspective on the issue and feel that a review of some of the more practical considerations is important. PMID- 26858952 TI - Perineural Injection for Treatment of Root-Signature Signs Associated with Lateralized Disk Material in Five Dogs (2009-2013). AB - Intervertebral disk disease (IVDD) is common in dogs; cervical IVDD accounts for 13-25% of all cases. Ventral slot decompression provides access to ventral and centrally extruded or protruded disk material. However, procedures to remove dorsally or laterally displaced material are more difficult. This case series describes the use of perineural injection as a potential treatment option for dogs experiencing root-signature signs associated with lateralized disk material in the cervical spine. Five dogs underwent fluoroscopically guided perineural injection of methylprednisolone +/- bupivacaine. Most patients experienced improvement in root-signature signs and remained pain free without the assistance of oral pain medication. These findings suggest the perineural injection of methylprednisolone +/- bupivacaine represents a viable option for dogs with cervical lateralized disk material causing root-signature signs. PMID- 26858953 TI - Blackpatch of Clover, Cause of Slobbers Syndrome: A Review of the Disease and the Pathogen, Rhizoctonia leguminicola. AB - Rhizoctonia leguminicola Gough and Elliott is a widely used name for the causal agent of blackpatch disease of red clover (Trifolium pratense L.). This fungal pathogen produces alkaloids (slaframine and swainsonine) that affect grazing mammals. Slaframine causes livestock to salivate profusely, and swainsonine causes neurological problems. Although the blackpatch fungus was classified as a Rhizoctonia species (phylum Basidiomycota), morphological studies have indicated that it is in the phylum Ascomycota, and sequencing data have indicated that it may be a new genus of ascomycete. The effects of the alkaloids on grazing mammals and their biosynthetic pathways have been extensively studied. In contrast, few studies have been done on management of the disease, which requires a greater understanding of the pathogen. Methods of disease management have included seed treatments and fungicides, but these have not been investigated since the 1950s. Searches for resistant cultivars have been limited. This review summarizes the biological effects and biosynthetic precursors of slaframine and swainsonine. Emphasis is placed on current knowledge about the epidemiology of blackpatch disease and the ecology and taxonomy of the pathogen. Possibilities for future research and disease management efforts are suggested. PMID- 26858954 TI - Comment on "The Prevalence of Skilled Birth Attendant Utilization and Its Correlates in North West Ethiopia". PMID- 26858955 TI - Attitudes towards Advance Care Planning and Healthcare Autonomy among Community Dwelling Older Adults in Beijing, China. AB - OBJECTIVES: To investigate the preferences of ACP and healthcare autonomy in community-dwelling older Chinese adults. METHODS: A community-based cross sectional study was conducted with older adults living in the residential estate of Chaoyang District, Beijing. RESULTS: 900 residents were enrolled. 80.9% of them wanted to hear the truth regarding their own condition from the physician; 52.4% preferred to make their own healthcare decisions. Only 8.9% of them preferred to endure life-prolonging interventions when faced with irreversible conditions. 78.3% of the respondents had not heard of an ACP; only 39.4% preferred to document in an ACP. Respondents with higher education had significantly higher proportion of having heard of an ACP, as well as preferring to document in an ACP, compared to those with lower education. Those aged <70 years had higher proportion of having heard of an ACP, as well as refusing life prolonging interventions when faced with irreversible conditions, compared to those aged >= 70 years. CONCLUSIONS: Although the majority of community-dwelling older Chinese adults appeared to have healthcare autonomy and refuse life prolonging interventions in terms of end-of-life care, a low level of "Planning ahead" awareness and preference was apparent. Age and education level may be the influential factors. PMID- 26858956 TI - Vocal Fold Augmentation with Beta Glucan Hydrogel Cross-Linked by gamma Irradiation for Enhanced Duration of Effect: In Vivo Animal Study. AB - This study explored a novel strategy to restore the vocal gap by using cross linked beta-glucan hydrogel by gamma-irradiation. An aqueous solution of 5 wt% beta-glucan was prepared and cross-linked using (60)Co gamma irradiation. Ten nude mice were injected with 0.8 mL of irradiated beta-glucan on the left back and the same volume of nonirradiated beta-glucan on the right back for comparison. The mice were sacrificed at 1 and 2 weeks after injection and histological evaluations were performed. Irradiated beta-glucan demonstrated a significantly larger volume than nonirradiated beta-glucan in the back of nude mice with less inflammatory reaction. After unilateral recurrent laryngeal nerve section in New Zealand White rabbits, irradiated and nonirradiated beta-glucan were injected into paralyzed vocal folds. Irradiated beta-glucan remained at the paralyzed vocal fold without definite inflammatory signs on endoscopy. High-speed recordings of vocal fold vibration showed decreased vocal gap in irradiated group compared to nonirradiated group. Histologically, the laryngeal epithelium and lamina propria remained intact, without inflammatory cell infiltration. Our newly developed injection material, irradiated beta-glucan, showed excellent biocompatibility and remained longer than nonirradiated beta-glucan in vivo, suggesting irradiated hydrogels as a new therapeutic approach that may be useful for the long-term treatment of vocal fold palsy. PMID- 26858958 TI - Effectiveness of a Peer Support Programme versus Usual Care in Disease Management of Diabetes Mellitus Type 2 regarding Improvement of Metabolic Control: A Cluster Randomised Controlled Trial. AB - AIM: Testing the effectiveness of peer support additionally to a disease management programme (DMP) for type 2 diabetes patients. METHODS: Unblinded cluster-randomised controlled trial (RCT) involving 49 general practices, province of Salzburg, Austria. All patients enrolled in the DMP were eligible, n = 337 participated (intervention: 148 in 19 clusters; control: 189 in 20 clusters). The peer support intervention ran over 24 months and consisted of peer supporter recruitment and training, and group meetings weekly for physical exercise and monthly for discussion of diabetes related topics. RESULTS: At two year follow-up, adjusted analysis revealed a nonsignificant difference in HbA1c change of 0.14% (21.97 mmol/mol) in favour of the intervention (95% CI -0.08 to 0.36%, p = 0.22). Baseline values were 7.02 +/- 1.25% in the intervention and 7.08 +/- 1.25 in the control group. None of the secondary outcome measures showed significant differences except for improved quality of life (EQ-5D-VAS) in controls (4.3 points on a scale of 100; 95% CI 0.08 to 8.53, p = 0.046) compared to the intervention group. CONCLUSION: Our peer support intervention as an additional DMP component showed no significant effect on HbA1c and secondary outcome measures. Further RTCs with a longer follow-up are needed to reveal whether peer support will have clinically relevant effects. TRIAL REGISTRATION: This trial has been registered with Current Controlled Trials Ltd. (ISRCTN10291077). PMID- 26858959 TI - Breaking the Taboo: Illicit Drug Use among Adolescents with Type 1 Diabetes Mellitus. AB - BACKGROUND: The aim of the study was to explore the prevalence of illicit drug use in a group of Polish adolescents with type 1 diabetes (DM1) in comparison with a national cohort of their healthy peers. METHODS: Two hundred and nine adolescents with DM1, aged 15-18 years, were studied in 2013 with an anonymous questionnaire prepared for the European School Survey Project on Alcohol and Other Drugs (ESPAD). The control group was a representative sample of 12114 students at the same age who took part in ESPAD in 2011. Metabolic control was regarded as good if self-reported HbA1c was <8% or poor if HbA1c was >=8%. RESULTS: Lifetime prevalence of illicit drug use was lower among adolescents with DM1 than in the control group [58 (28%) versus 5524 (46%), p = 10(-5)]. Cannabis preparations were the most frequently used substances [38 (18.3%) versus 3976 (33.1%), p = 10(-5)], followed by tranquilizers, sedatives, and amphetamine. Lifetime and last 12-month use of cannabis were associated with poorer glycemic control (HbA1c >= 8%), p < 0.01 and 0.02, respectively. CONCLUSIONS: Adolescents with DM1 report using illicit drugs to a lesser extent than their healthy peers. The use of cannabis is associated with a poorer metabolic control in teens with DM1. PMID- 26858960 TI - Long-term outcomes of endothelial keratoplasty in Chinese eyes at a University Hospital. AB - BACKGROUND: Endothelial keratoplasty (EK) is used increasingly for the management of cases with endothelial dysfunction. Long-term outcomes of the surgery are not widely reported in the literature. We report our experience of EK in Chinese eyes at a University teaching hospital. METHODS: Retrospective analysis was performed for all cases of EK performed between 2005 and 2009. Data analyzed included indication for surgery, associated surgical procedures, complications, best corrected visual acuity (BCVA) and overall graft survival. RESULTS: Overall, 22 eyes of 21 patients underwent EK (13 males, 8 females, mean age 71.8 +/- 11.3 years). Pseudophakic bullous keratopathy was the leading indication for surgery (n = 12) followed by Fuchs' endothelial dystrophy (n = 4), or both (n = 3). Other indications for surgery included failed penetrating keratoplasty (n = 2) and endothelial decompensation due to multiple surgeries (n = 1). Triple procedure was performed in 5 (22.7%) cases. Complications were noted in the form of postoperative interface hemorrhage (n = 2, 9%) and graft dislocation (n = 1, 4.5%). The mean postoperative endothelial cell density was 1069 +/- 585.8 cells/mm(2). The mean postoperative pachymetry was 675.8 +/- 108.5 MUm. The mean preoperative and postoperative intraocular pressure was 11.3 +/- 3.2 and 13.9 +/- 4.5 mmHg respectively. At the last follow-up (mean, 47.4 +/- 13.7 months), BCVA was >=20/70 in 9 (40.9%) cases. Causes of poor BCVA included primary graft failure (n = 4), graft decompensation (n = 4), advanced glaucoma (n = 2) and irreversible graft rejection (n = 2). Graft remained clear in 12 (54.5%) cases at the last follow-up. Average graft survival was 19.7 +/- 17.7 months (median 17.5 months). CONCLUSIONS: Nearly half of the EK grafts in our study survived over a period of five years. Graft failure, glaucoma and graft rejection were the main causes of poor graft survival. PMID- 26858962 TI - A Case of Long-Term Seronegative Human Immunodeficiency Virus (HIV) Infection: The Importance of the Humoral Response to HIV. AB - Background. Seronegative human immunodeficiency virus (HIV) infections are exceedingly rare but might inform HIV-host physiology. Methods. We investigate the cause and consequences of a patient infected with HIV who did not mount a humoral response to HIV for 4 years. Results. The patient was confirmed HIV uninfected by nucleic acid testing 4 months before rapidly progressing to acquired immune deficiency syndrome. The patient's humoral deficit was specific to HIV: he mounted robust humoral responses to all challenge vaccines including influenza A(H1N1)pdm09 and all T cell-dependent and -independent serotypes in the 23-valent pneumococcal polysaccharide vaccine. The virus had similar gp120 antigenicity to HIV-positive control serum as NL4-3 and YU2 prototype strains. Two human leukocyte antigen alleles associated with rapid progression were identified (B*08 and B*35), and a cytotoxic T-lymphocyte epitope site variant was noted: E277K. Viral decay (t 1/2 ~ 39 weeks) suggested that relatively long-lived cells were the source of ongoing viremia. Human immunodeficiency virus viremia was not suppressed until after the patient developed a humoral immune response, despite therapeutic antiretroviral levels. No resistance was detected by virtual phenotyping of virus obtained from serum or from gastrointestinal biopsies despite considerable antiretroviral selection pressure. Conclusions. Ineffective antibody production may be associated with a subgroup of extremely rapid HIV progressors. Although antiretroviral therapy may be sufficient to slow propagation of infection, it appears to be ineffective for HIV viral clearance in the absence of a humoral response. PMID- 26858961 TI - Candida Arthritis: Analysis of 112 Pediatric and Adult Cases. AB - Background. Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood. Methods. Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome. Results. Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range, <1-84 years). Most patients (65%) were not pharmacologically immunosuppressed. Polyarticular infection (>=3 joints) occurred in 31% of cases. Clinical manifestations included pain (82%), edema (71%), limited function (39%), and erythema (22%) with knees (75%) and hips (15%) most commonly infected. Median erythrocyte sedimentation rate was 62 mm/hr (10-141) and C reactive protein 26 mg/dL (0.5-95). Synovial fluid median white blood cell count was 27 500/uL (range, 100-220 000/uL) with 90% polymorphonuclear neutrophils (range, 24-98). Adjacent osteomyelitis was present in 30% of cases. Candida albicans constituted 63%, Candida tropicalis 14%, and Candida parapsilosis 11%. Most cases (66%) arose de novo, whereas 34% emerged during antifungal therapy. Osteolysis occurred in 42%, joint-effusion in 31%, and soft tissue extension in 21%. Amphotericin and fluconazole were the most commonly used agents. Surgical interventions included debridement in 25%, irrigation 10%, and drainage 12%. Complete or partial response was achieved in 96% and relapse in 16%. Conclusion. Candida arthritis mainly emerges as a de novo infection in usually non-immunosuppressed patients with hips and knees being most commonly infected. Localizing symptoms are frequent, and the most common etiologic agents are C albicans, C tropicalis, and C parapsilosis. Management of Candida arthritis remains challenging with a clear risk of relapse, despite antifungal therapy. PMID- 26858957 TI - Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma. AB - We would like to highlight the application of natural products to hepatocellular carcinoma (HCC). We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signaling pathways and serve as antioxidants. In this review, we will discuss seven common flavonoids that exert different biological effects against HCC via different pathways. PMID- 26858963 TI - Manufacturing of AcMNPV baculovirus vectors to enable gene therapy trials. AB - Over the past two decades, baculoviruses have become workhorse research tools for transient transgene expression. Although they have not yet been used directly as a gene therapy vector in the clinical setting, numerous preclinical studies have suggested the highly promising potential of baculovirus as a delivery vector for a variety of therapeutic applications including vaccination, tissue engineering, and cancer treatment. As such, there is growing interest in using baculoviruses as human gene therapy vectors, which has led to advances in baculovirus bioprocessing methods. This review provides an overview of the current approaches for scaled-up amplification, concentration, purification, and formulation of AcMNPV baculoviruses, and highlights the key regulatory requirements that must be met before gene therapy clinical trials can be initiated. PMID- 26858965 TI - Rapid cloning, expression, and functional characterization of paired alphabeta and gammadelta T-cell receptor chains from single-cell analysis. AB - Transgenic expression of antigen-specific T-cell receptor (TCR) genes is a promising approach for immunotherapy against infectious diseases and cancers. A key to the efficient application of this approach is the rapid and specific isolation and cloning of TCRs. Current methods are often labor-intensive, nonspecific, and/or relatively slow. Here, we describe an efficient system for antigen-specific alphabetaTCR cloning and CDR3 substitution. We demonstrate the capability of cloning influenza-specific TCRs within 10 days using single-cell polymerase chain reaction (PCR) and Gibson Assembly techniques. This process can be accelerated to 5 days by generating receptor libraries, requiring only the exchange of the antigen-specific CDR3 region into an existing backbone. We describe the construction of this library for human gammadelta TCRs and report the cloning and expression of a TRGV9/TRDV2 receptor that is activated by zoledronic acid. The functional activity of these alphabeta and gammadelta TCRs can be characterized in a novel reporter cell line (Nur77-GFP Jurkat 76 TCRalpha( )beta(-)) for screening of TCR specificity and avidity. In summary, we provide a rapid method for the cloning, expression, and functional characterization of human and mouse TCRs that can assist in the development of TCR-mediated therapeutics. PMID- 26858966 TI - Compared to what: What can we say about nonapeptide function and social behavior without a frame of reference? AB - Our understanding of behavior and mechanism is undermined by the absence of a frame of reference because relationships between individuals and species are without context. We highlight a need to be more comparative, using nonapeptide (vasopressin and oxytocin) modulation of social behavior as an example. We reconsider the use of model organisms and the term 'social' in this context, contrasting two popular models for nonapeptide regulation of social behavior. We then propose that a frame of reference should be established by studying mechanisms of behavior across taxa along the same continua. If we are to ever establish a unifying theory of behavior, we must transcend individual examples and determine the relative relationships of behavior and mechanism among and between species. PMID- 26858964 TI - Targeted approaches to induce immune tolerance for Pompe disease therapy. AB - Enzyme and gene replacement strategies have developed into viable therapeutic approaches for the treatment of Pompe disease (acid alpha-glucosidase (GAA) deficiency). Unfortunately, the introduction of GAA and viral vectors encoding the enzyme can lead to detrimental immune responses that attenuate treatment benefits and can impact patient safety. Preclinical and clinical experience in addressing humoral responses toward enzyme and gene therapy for Pompe disease have provided greater understanding of the immunological consequences of the provided therapy. B- and T-cell modulation has been shown to be effective in preventing infusion-associated reactions during enzyme replacement therapy in patients and has shown similar success in the context of gene therapy. Additional techniques to induce humoral tolerance for Pompe disease have been the targeted expression or delivery of GAA to discrete cell types or tissues such as the gut associated lymphoid tissues, red blood cells, hematopoietic stem cells, and the liver. Research into overcoming preexisting immunity through immunomodulation and gene transfer are becoming increasingly important to achieve long-term efficacy. This review highlights the advances in therapies as well as the improved understanding of the molecular mechanisms involved in the humoral immune response with emphasis on methods employed to overcome responses associated with enzyme and gene therapies for Pompe disease. PMID- 26858967 TI - Integrating molecular mechanisms into quantitative genetics to understand consistent individual differences in behavior. AB - It is now well appreciated that individual animals behave differently from one another and that individual differences in behaviors-personality differences-are maintained through time and across situations. Quantitative genetics has emerged as a conceptual basis for understanding the key ingredients of personality: (co)variation and plasticity. However, the results from quantitative genetic analyses are often divorced from underlying molecular or other proximate mechanisms. This disconnect has the potential to impede an integrated understanding of behavior and is a disconnect present throughout evolutionary ecology. Here we discuss some of the main conceptual connections between personality and quantitative genetics, the relationship of both with genomic tools, and areas that require integration. With its consideration of both trait variation and plasticity, the study of animal personality offers new opportunities to incorporate molecular mechanisms into both the trait partitioning and reaction norm frameworks provided by quantitative genetics. PMID- 26858968 TI - New perspectives on vasoactive intestinal polypeptide as a widespread modulator of social behavior. AB - In terms of reproductive and social functions, vasoactive intestinal polypeptide (VIP) is best known as a major regulator of prolactin secretion in vertebrates and hence, as an essential contributor to parental care. However, VIP and its cognate VPAC receptors are distributed throughout the social behavior network in the brain, suggesting that VIP circuits may play important roles in a variety of behaviors. With the exception of VIP neuronal populations in the suprachiasmatic nucleus and tuberal hypothalamus (which regulate circadian rhythms and prolactin secretion, respectively), we have known very little about the functional properties of VIP circuits until recently. The present review highlights new roles for VIP signaling in avian social behaviors such as affiliation, gregariousness, pair bonding and aggression, and discusses recent advances in VIP's role as a regulator of biological rhythms, including the potential timing of ovulation, photoperiodic response and seasonal migration. PMID- 26858969 TI - Developmental immune activation programs adult behavior: insight from research on birds. AB - Immune activation early in life can program adult behavioral expression. Previous research on birds has documented effects of parasite exposure and immune challenges early in life on dispersal, song, personality, learning and feather pecking. However, the mechanisms responsible for mediating these programming effects are unknown. Candidate brain regions that may be most sensitive include the hippocampus and HVC. Without an understanding of mechanism, it is difficult to assess if programmed behaviors represent pathological side effects or behavioral modifications with benefits to either hosts or parasites. Future research on birds promises to provide novel insight into the adaptive value of programming effects of early life immune activation and the capacity for selection to buffer hosts against negative effects. PMID- 26858970 TI - Effects of mothers' and fathers' experience with predation risk on the behavioral development of their offspring in threespined sticklebacks. AB - Stressors experienced by parents can influence the behavioral development of their offspring. Here, we review recent studies in threespined sticklebacks (a species in which males are the sole providers of parental care) showing that when parents are exposed to an ecologically relevant stressor (predation risk), there are consequences for offspring. For example, female sticklebacks exposed to predation risk produce eggs with higher concentrations of cortisol, a stress hormone, and offspring with altered behavior and physiology. Male sticklebacks exposed to predation risk produce offspring that are less active, smaller, and in poorer condition. The precise mechanisms by which maternal and paternal experiences with predators affect offspring phenotypes are under investigation, and could include steroid hormones, olfactory cues and/or parental behavior. As in other species, some of the consequences of parental exposure to predation risk for offspring in sticklebacks might be adaptive, but depend on the stressor, the reliability of the parental and offspring environments and the evolutionary history of the population. PMID- 26858971 TI - Early-life Social Adversity and Developmental Processes in Nonhuman Primates. AB - Most primate species produce offspring that are altricial and highly dependent upon caregivers. As a consequence, a host of developmental trajectories can be dramatically altered by variation in early experiences. We review the impact of early social experiences (in both experimental models and natural contexts) on developmental profiles in three species of nonhuman primates: marmosets, squirrel monkeys, and macaques. Graded exposure to early-life social adversity (ELSA) produces short- to long-term effects on multiple developmental outcomes, including affect, social behavior, cognitive and attentional processes, and in the neural substrates that underlie these sociobehavioral traits. PMID- 26858973 TI - Metagenomic data of the bacterial community in coastal Gulf of Mexico sediment microcosms following exposure to Macondo oil (MC252). AB - The data in this article includes the sequences of bacterial 16S rRNA gene from metagenome of Macondo oil (MC252)-treated and non-oil-treated sediment microcosms, collected from coastal Gulf of Mexico and Bayou La Batre, USA. Metacommunity DNA was PCR amplified with 341F and 907R oligonucleotide primers, targeting V3-V5 regions of the 16S rRNA gene. Data were generated by using bacterial tag-encoded FLX-amplicon pyrosequencing (bTEFAP) methodology and then processed using bioinformatics tools such as QIIME. The data information is deposited to NCBI's BioProject and BioSample and raw sequence files are available via NCBI's Sequence Read Archive (SRA) database. PMID- 26858972 TI - Early life exposure to obesogenic diets and learning and memory dysfunction. AB - Obesogenic dietary factors, such as simple sugars and saturated fatty acids, have been linked to memory impairments and hippocampal dysfunction. Recent evidence suggests that the brain may be particularly vulnerable to the effects of obesogenic diets during early life periods of rapid growth, maturation, and brain development. Investigations utilizing rodent models indicate that early life exposure to "high fat diets" (40-65% kcal derived from fat) or simple sugars (sucrose or high fructose corn syrup) can impair hippocampus-dependent learning and memory processes. In some cases, these deficits occur independent of obesity and metabolic derangement and can persist into adulthood despite dietary intervention. Various neurobiological mechanisms have been identified that may link early life consumption of obesogenic dietary factors with hippocampal dysfunction, including increased neuroinflammation and reduced neurotrophin mediated regulation of neurogenesis and synaptic plasticity. Age, duration of exposure, and dietary composition are key variables contributing to the interaction between early life diet and cognitive dysfunction, however, more research is needed to unravel the precise critical windows of development and causal dietary factors. PMID- 26858974 TI - Vinculin expression in MC3T3-E1 cells in response to mechanical stimulus. AB - Loading frequency is known to influence the expression of the focal adhesions of the adherent cells. A small cyclical tensile force was transmitted to mouse pre osteoblast MC3T3-E1 cells through PDMS substrates of varying stiffness. Changes in cell behavior with respect to proliferation and characteristics of focal adhesions were quantified through immunofluorescence labeling of vinculin. Amount of inactive vinculin was higher on substrates subjected to cyclic stimulation when compared with the results of the static substrates, whereas the number and area of focal adhesion points underwent a reduction. Inactive vinculin appears as a cloud in the cytoplasm in the vicinity of the nucleus. PMID- 26858975 TI - Gene expression profiling data of Schizosaccharomyces pombe under nitrosative stress using differential display. AB - Excess production of nitric oxide (NO) and reactive nitrogen intermediates (RNIs) causes nitrosative stress on cells. Schizosaccharomyces pombe was used as a model to study nitrosative stress response. In the present data article, we have used differential display to identify the differentially expressed genes in the fission yeast under nitrosative stress conditions. We have used pure NO donor compound detaNONOate at final concentrations of 0.1 mM and 1 mM to treat the cells for 15 min alongside control before studying their gene expression profiles. At both the treated conditions, we identified genes which were commonly repressed while several genes were induced upon both 0.1 mM and 1 mM treatments. The differentially expressed genes were further analyzed in DAVID and categorized into several different pathways. PMID- 26858977 TI - Evidence for Dsg3 in regulating Src signaling by competing with it for binding to caveolin-1. AB - This data article contains extended, complementary analysis related to the research articles entitled "Desmoglein 3, via an interaction with E-cadherin, is associated with activation of Src" (Tsang et al., 2010) [1] and figures related to the review article entitled "Desmoglein 3: a help or a hindrance in cancer progression?" (Brown et al., 2014) [2]. We show here that both Src and caveolin-1 (Cav-1) associate with Dsg3 in a non-ionic detergent soluble pool and that modulation of Dsg3 levels inversely alters the expression of Src in the Cav-1 complex. Furthermore, immunofluorescence analysis revealed a reduced colocalization of Cav-1/total Src in cells with overexpression of Dsg3 compared to control cells. In support, the sequence analysis has identified a region within the carboxyl-terminus of human Dsg3 for a likelihood of binding to the scaffolding domain of Cav-1, the known Src binding site in Cav-1, and this region is highly conserved across most of 18 species as well as within desmoglein family members. Based on these findings, we propose a working model that Dsg3 activates Src through competing with its inactive form for binding to Cav-1, thus leading to release of Src followed by its auto-activation. PMID- 26858976 TI - Detection bias in microarray and sequencing transcriptomic analysis identified by housekeeping genes. AB - This work includes the original data used to discover the gene ontology bias in transcriptomic analysis conducted by microarray and high throughput sequencing (Zhang et al., 2015) [1]. In the analysis, housekeeping genes were used to examine the differential detection ability by microarray and sequencing because these genes are probably the most reliably detected. The genes included here were compiled from 15 human housekeeping gene studies. The provided tables here comprise of detailed chromosomal location, detection breadth, normalized expression level, exon count, total exon length, and total intron length of each concerned gene and their related transcripts. We hope this information can help researchers better understand the differences in gene ontology-bias we discussed (Zhang et al., 2015) [1] and can encourage further improvement on these two technology platforms. PMID- 26858978 TI - Quantitative analysis of hormones and inflammatory cytokines in Chlamydia trachomatis-infected women with tubal ectopic pregnancy and early intrauterine pregnancy. AB - In this data, non-pregnant women during the menstrual cycle, women with normal intrauterine pregnancy (IUP), and women with tubal ectopic pregnancy (EP) after informed consent were included. The serum levels of 17beta-estradiol, progesterone, testosterone, beta-human chorionic gonadotropin, interleukin (IL) 1beta, IL-4, IL-6, IL-7, IL-8, IL-10, tumor necrosis factor alpha (TNFalpha), and interferon-gamma (IFN-gamma), epidermal growth factor, the Chlamydia (C.) trachomatis IgG and HSP60 were analyzed. Receiver operating characteristic analysis was used to assess the diagnostic discrimination of tubal EP and gestational age-matched IUP. Our data show that C. trachomatis infection is associated with IL-8 levels, which had excellent discriminative validity in positively identifying tubal EP (concomitant with C. trachomatis infection) from IUP and non-pregnant conditions regardless of C. trachomatis infection. PMID- 26858979 TI - A compilation of ab-initio calculations of embrittling potencies in binary metallic alloys. AB - Segregation-induced changes in interfacial cohesion often control the mechanical properties of metals. The change in the work of separation of an interface upon segregation of a solute to the interface, termed the embrittling potency, is an atomic-level quantity used to predict and understand embrittlement phenomena. We present a compilation of calculations of embrittling potencies, along with references for these calculations. A discussion of this data is made in a separate article (Gibson and Schuh, 2016 [1]). PMID- 26858980 TI - Data on thrombotic ischemic lesions in the presence or absence of amyloid beta protein precursor or its homolog amyloid precursor-like protein-2 in mice. AB - Amyloid beta-protein precursor (AbetaPP) and amyloid precursor-like protein-2 (APLP2) are potent inhibitors of thrombosis, see related article "The influence of the amyloid beta-protein and its precursor in modulating cerebral thrombosis" (Van Nostrand, 2016) [1]. Datapresented are images of photo-induced thrombotic ischemic stroke in wild-type mice, AbetaPP(-) (/) (-) mice and APLP2(-) (/) (-) mice, and the calculated infarct volume show approximately 40% and 33%, respectively, larger cerebral infarcts compared to wild-type mice. PMID- 26858982 TI - Data in support of FSH induction of IRS-2 in human granulosa cells: Mapping the transcription factor binding sites in human IRS-2 promoter. AB - Insulin receptor substrate-2 (IRS-2) plays critical role in the regulation of various metabolic processes by insulin and IGF-1. The defects in its expression and/or function are linked to diseases like polycystic ovary syndrome (PCOS), insulin resistance and cancer. To predict the transcription factors (TFs) responsible for the regulation of human IRS-2 gene expression, the transcription factor binding sites (TFBS) and the corresponding TFs were investigated by analysis of IRS-2 promoter sequence using MatInspector Genomatix software (Cartharius et al., 2005 [1]). The ibid data is part of author's publication (Anjali et al., 2015 [2]) that explains Follicle stimulating hormone (FSH) mediated IRS-2 promoter activation in human granulosa cells and its importance in the pathophysiology of PCOS. Further analysis was carried out for binary interactions of TF regulatory genes in IRS-2 network using Cytoscape software tool and R-code. In this manuscript, we describe the methodology used for the identification of TFBSs in human IRS-2 promoter region and provide details on experimental procedures, analysis method, validation of data and also the raw files. The purpose of this article is to provide the data on all TFBSs in the promoter region of human IRS-2 gene as it has the potential for prediction of the regulation of IRS-2 gene in normal or diseased cells from patients with metabolic disorders and cancer. PMID- 26858981 TI - Synthesis of novel ICIE16/BSG and ICIE16/BSG-NITRI bioglasses and description of ionic release kinetics upon immersion in SBF fluid: Effect of nitridation. AB - A novel bioactive glass scaffold ICIE16/BSG has been prepared from a mixture of two different melt-derived glasses: a silicate bioglass (ICIE16) and a borosilicate bioglass (BSG). Combined processing techniques (gel casting and foam replication) were used to form three-dimensional, interconnected porous monolith scaffolds (Orgaz et al., 2016) [1]. They were then nitrided with a hot ammonia flow as described in (Aleixandre et al., 1973) [3] and (Nieto, 1984) [4] to synthesize the ICIE16/BSG-NITRI bioglass (Orgaz et al., 2016) [1]. Herein we present a flow chart summarizing the forming process, plus images of the resulting scaffold after sintering and drying. Bioactivity was characterized in vitro by immersion in simulated body fluid (SBF) for up to seven days. Data of ionic release kinetics upon SBF immersion are presented. PMID- 26858983 TI - Influence of a family 29 carbohydrate binding module on the recombinant production of galactose oxidase in Pichia pastoris. AB - Herein, we report the extracellular expression of carbohydrate active fusion enzymes in Pichia pastoris. Particularly, CBM29-1-2 from Piromyces equi was separately fused to the N- and C-terminus of galactose 6-oxidase (GaO, D galactose: oxygen 6-oxidoreductase, EC 1.1.13.9, CAZy family AA5) from Fusarium graminearum, generating CBM29-GaO and GaO-CBM29, respectively. P. pastoris was transformed with expression vectors encoding GaO, CBM29-GaO and GaO-CBM29, and the fusion proteins were expressed in both shake-flask and 2L bioreactor systems. Volumetric production yields and specific GaO activity increased when expression was performed in a bioreactor system compared to shake-flask cultivation. This was observed for both CBM29-GaO and GaO-CBM29, and is consistent with previous reports of GaO expression in P. pastoris (Spadiut et al., 2010; Anasontzis et al., 2014) [1], [2]. Fusion of CBM29 to the C-terminal of GaO (GaO-CBM29) resulted in a stable uniform protein at the expected calculated size (107 kDa) when analyzed with SDS-PAGE. By comparison, the expression of the N-terminal fusion protein (CBM29-GaO) was low, and two truncated versions of CBM29-GaO were coexpressed with the full-sized protein. Despite differences in protein yield, the specific GaO activity on galactose was not affected by CBM29 fusion to either the N- or C-terminus of the enzyme. A detailed description of the catalytic and physiochemical properties of CBM29-GaO and GaO-CBM29 is available in the parent publication (Mollerup et al., 2015) [3]. PMID- 26858984 TI - A Case of Cutaneous Rosai-Dorfman Disease with underlying calvarial involvement and absence of BRAFV600E mutation. PMID- 26858985 TI - Visual Adaptation. AB - Sensory systems continuously mold themselves to the widely varying contexts in which they must operate. Studies of these adaptations have played a long and central role in vision science. In part this is because the specific adaptations remain a powerful tool for dissecting vision, by exposing the mechanisms that are adapting. That is, "if it adapts, it's there." Many insights about vision have come from using adaptation in this way, as a method. A second important trend has been the realization that the processes of adaptation are themselves essential to how vision works, and thus are likely to operate at all levels. That is, "if it's there, it adapts." This has focused interest on the mechanisms of adaptation as the target rather than the probe. Together both approaches have led to an emerging insight of adaptation as a fundamental and ubiquitous coding strategy impacting all aspects of how we see. PMID- 26858986 TI - The Use of Low Level Laser Therapy (LLLT) For Musculoskeletal Pain. AB - Pain is the most common reason for physician consultation in the United States. One out of three Americans is affected by chronic pain annually. The number one reason for missed work or school days is musculoskeletal pain. Currently accepted therapies consist of non-steroidal anti-inflammatory drugs, steroid injections, opiate pain medications and surgery, each of which carries their own specific risk profiles. What is needed are effective treatments for pain which have an acceptably low risk-profile. For over forty years, low level laser (light) therapy (LLLT) and LED (light emitting diode) therapy (also known as photobiomodulation) has been shown to reduce inflammation and edema, induce analgesia, and promote healing in a range of musculoskeletal pathologies. The purpose of this paper is to review the use of LLLT for pain, the biochemical mechanisms of action, the dose response curves, and how LLLT may be employed by orthopedic surgeons to improve outcomes and reduce adverse events. With the predicted epidemic of chronic pain in developed countries, it is imperative to validate cost-effective and safe techniques for managing painful conditions which would allow people to live active and productive lives. Moreover the acceptance of LLLT (which is currently being used by many specialties around the world) into the armamentarium of the American health care provider would allow for additional treatment options for patients. A new cost-effective therapy for pain could elevate quality of life while reducing financial strains. PMID- 26858987 TI - Application of 212Pb for Targeted alpha-particle Therapy (TAT): Pre-clinical and Mechanistic Understanding through to Clinical Translation. AB - Targeted alpha-particle therapy (TAT), in which an alpha-particle emitting radionuclide is specifically directed to a biological target, is gaining more attention to treat cancers as new targets are validated. Bio-vectors such as monoclonal antibodies are able to selectively transport alpha-particles to destroy targeted cancer cells. TAT has the potential for an improved therapeutic ratio over beta-particle targeted conjugate therapy. The short path length and the intense ionization path generated render alpha-emitters suitable for treatment and management of minimal disease such as micrometastases or residual tumor after surgical debulking. 212Pb is the longer-lived parent radionuclide of 212Bi and serves as an in vivo generator of 212Bi. 212Pb has demonstrated significant utility in both in vitro and in vivo models. Recent evaluation of 212Pb-TCMC-trastuzumab in a Phase I clinical trial has demonstrated the feasibility of 212Pb in TAT for the treatment of ovarian cancer patients. This review highlights progress in radionuclide production, radiolabeling chemistry, molecular mechanisms, and application of 212Pb to targeted pre-clinical and clinical radiation therapy for the management and treatment of cancer. PMID- 26858989 TI - The journey of DNA repair. AB - 21 years ago, the DNA Repair Enzyme was declared "Molecule of the Year". Today, we are celebrating another "year of repair", with the 2015 Nobel Prize in Chemistry being awarded to Aziz Sancar, Tomas Lindahl and Paul Modrich for their collective work on the different DNA repair pathways. PMID- 26858988 TI - Targeting RAS-mutant cancers: is ERK the key? AB - The three RAS genes comprise the most frequently mutated oncogene family in cancer. With significant and compelling evidence that continued function of mutant RAS is required for tumor maintenance, it is widely accepted that effective anti-RAS therapy will have a significant impact on cancer growth and patient survival. However, despite more than three decades of intense research and pharmaceutical industry efforts, a clinically effective anti-RAS drug has yet to be developed. With the recent renewed interest in targeting RAS, exciting and promising progress has been made. In this review, we discuss the prospects and challenges of drugging oncogenic RAS. In particular we focus on new inhibitors of RAS effector signaling and the ERK mitogen-activated protein kinase cascade. PMID- 26858990 TI - Microfluidics: A new tool for modeling cancer-immune interactions. AB - In recognition of the enormous potential of immunotherapies against cancer, research into the interactions between tumor and immune cells has accelerated, leading to the recent FDA approval of several drugs that reduce cancer progression. Numerous cellular and molecular interactions have been identified by which immune cells can intervene in the metastatic cascade, leading to the development of several in vivo and in vitro model systems that can recapitulate these processes. Among these, microfluidic technologies hold many advantages in terms of their unique ability to capture the essential features of multiple cell type interactions in three-dimensions while allowing tight control of the microenvironment and real-time monitoring. Here, we review current assays and discuss the development of new microfluidic technologies for immunotherapy. PMID- 26858991 TI - Neuroimaging genetic risk for Alzheimer's disease in preclinical individuals: From candidate genes to polygenic approaches. AB - Better characterization of the preclinical phase of Alzheimer's disease (AD) is needed in order to develop effective interventions. Neuropathological changes in AD, including neuronal loss and the formation of proteinaceous deposits, begin up to 20 years before the onset of clinical symptoms. As such, the emergence of cognitive impairment should not be the sole basis used to diagnose AD nor to evaluate individuals for enrollment in clinical trials for preventative AD treatments. Instead, early preclinical biomarkers of disease and genetic risk should be used to determine most likely prognosis and enroll individuals in appropriate clinical trials. Neuroimaging-based biomarkers and genetic analysis together present a powerful system for classifying preclinical pathology in patients. Disease modifying interventions are more likely to produce positive outcomes when administered early in the course of AD. In this review, we examine the utility of the neuroimaging genetics field as it applies to AD and early detection during the preclinical phase. Neuroimaging studies focused on single genetic risk factors are summarized. However, we particularly focus on the recent increased interest in polygenic methods and discuss the benefits and disadvantages of these approaches. We discuss challenges in the neuroimaging genetics field, including limitations of statistical power arising from small effect sizes and the over-use of cross-sectional designs. Despite the limitations, neuroimaging genetics has already begun to influence clinical trial design and will play a major role in the prevention of AD. PMID- 26858992 TI - Striatal magnetic resonance spectroscopy abnormalities in young adult SAPAP3 knockout mice. AB - BACKGROUND: Obsessive compulsive disorder (OCD) is a debilitating condition with lifetime prevalence of 1-3%. OCD typically arises in youth but delays in diagnosis impede optimal treatment and developmental studies of the disorder. Research using genetically modified rodents may provide models of etiology that enable earlier detection and intervention. The SAPAP3 knockout (KO) transgenic mouse was developed as an animal model of OCD and related disorders (OCRD). KO mice exhibit compulsive self-grooming behavior analogous to behaviors found in people with OCRD. Striatal hyperactivity has been reported in these mice and in humans with OCD. METHODS: Striatal and medial frontal cortex 9.4 Tesla proton spectra were acquired from young adult SAPAP3 KO and wild-type control mice to determine whether KO mice have metabolic and neurochemical abnormalities. RESULTS: Young adult KO mice had lower striatal lactate (P=0.006) and glutathione (P=0.039) levels. Among all mice, striatal lactate and glutathione levels were associated (R=0.73, P=0.007). We found no group differences in medial frontal cortex metabolites. At the age range studied, only 1 of 8 KO mice had skin lesions indicative of severe compulsive grooming. CONCLUSION: Young adult SAPAP3 KO mice have striatal but not medial frontal cortex MRS abnormalities that may reflect striatal hypermetabolism accompanied by oxidative stress. These abnormalities typically preceded the onset of severe compulsive grooming. Our findings are consistent with striatal hypermetabolism in OCD. Together, these results suggest that striatal MRS measures of lactate or glutathione might be useful biomarkers for early detection of risk for developing compulsive behavior disorders. PMID- 26858995 TI - A FRET-based biosensor for the detection of neutrophil elastase. AB - The direct and specific detection of biomarkers is crucial as it can allow monitoring the state of a tissue or wound as well as the progression of the inflammatory process. Neutrophil elastase (NE) plays an important role in many biological processes. It is involved in inflammatory diseases and is enriched in inflamed tissues, in wound exudate, and in the sputum of cystic fibrosis patients. In order to detect NE, we designed a NE-specific protein sensor whose fluorescence features are altered upon selective cleavage by NE at physiological concentration. The biosensor consists of two fluorescent GFP-derived proteins connected by a short peptide linker containing a NE-specific recognition sequence. Due to the close proximity of the two fluorescent proteins, Forster resonance energy transfer (FRET) occurs in the uncleaved form and, upon cleavage by NE, a decrease of FRET signal is observed. In this study, the construct design, the influence of the linker length, as well as the specificity for NE are described. Furthermore, the influence of biosensor immobilization on the functionality is analysed. By engineering the recognition sequence of the linker, the presented system can potentially be easily adapted to detect other proteases such as cathepsin, caspases or matrix metalloproteases. PMID- 26858993 TI - Rapid Changes in CB1 Receptor Availability in Cannabis Dependent Males after Abstinence from Cannabis. AB - BACKGROUND: The widespread use of cannabis, the increasing legalization of "medical" cannabis, the increasing potency of cannabis and the growing recreational use of synthetic cannabinoid 1 receptor (CB1R) full agonists underscores the importance of elucidating the effects of cannabinoids on the CB1R system. Exposure to cannabinoids is known to result in CB1R downregulation. However, the precise time course of changes in CB1R availability in cannabis dependent subjects (CDs) following short and intermediate term abstinence has not been determined. METHODS: Using High Resolution Research Tomography (HRRT) and [11C]OMAR, CB1R availability as indexed by the volume of distribution (VT) [11C]OMAR was measured in male CDs (n=11) and matched healthy controls (HCs) (n=19). CDs were scanned at baseline (while they were neither intoxicated nor in withdrawal), and after 2 days and 28 days of monitored abstinence. HCs were scanned at baseline and a subset (n=4) was rescanned 28 days later. RESULTS: Compared to HCs, [11C]OMAR VT was 15% lower in CDs (effect size Cohen's d=-1.11) at baseline in almost all brain regions. However, these group differences in CB1R availability were no longer evident after just 2 days of monitored abstinence from cannabis. There was a robust negative correlation between CB1R availability and withdrawal symptoms after 2 days of abstinence. Finally, there were no significant group differences in CB1R availability in CDs after 28 days of abstinence. CONCLUSIONS: Cannabis dependence is associated with CB1R downregulation, which begins to reverse surprisingly rapidly upon termination of cannabis use and may continue to increase over time. PMID- 26858996 TI - Unraveling near-field and far-field relationships for 3D SERS substrates--a combined experimental and theoretical analysis. AB - Simplicity and low cost has positioned inkjet paper- and fabric-based 3D substrates as two of the most commonly used surface-enhanced Raman spectroscopy (SERS) platforms for the detection and the identification of chemical and biological analytes down to the nanogram and femtogram levels. The relationship between far-field and near-field properties of these 3D SERS platforms remains poorly understood and warrants more detailed characterization. Here, we investigate the extremely weak optical scattering observed from commercial and home-fabricated paper-, as well as fabric-based 3D SERS substrates. Using wavelength scanned surface-enhanced Raman excitation spectroscopy (WS-SERES) and finite-difference time-domain (FDTD) calculations we were able to determine their near-field SERS properties and correlate them with morphological and far-field properties. It was found that nanoparticle dimers, trimers, and higher order nanoparticle clusters primarily determine the near-field properties of these substrates. At the same time, the far-field response of 3D SERS substrates either originates primarily from the monomers or cannot be clearly defined. Using FDTD we demonstrate that LSPR bands of nanoparticle aggregates near perfectly overlap with the maxima of the near-field surface-enhanced Raman scattering responses of the 3D SERS substrates. This behaviour of far-field spectroscopic properties and near-field surface-enhanced Raman scattering has not been previously observed for 2D SERS substrates, known as nanorod arrays. The combination of these analytical approaches provides a full spectroscopic characterization of 3D SERS substrates, while FDTD simulation can be used to design new 3D SERS substrates with tailored spectral characteristics. PMID- 26858994 TI - Blunted neural responses to reward in remitted major depression: A high-density event-related potential study. AB - BACKGROUND: Major depressive disorder (MDD) is a highly recurrent condition, and improving our understanding of the abnormalities that persist in remitted MDD (rMDD) may provide insight into mechanisms that contribute to relapse. MDD has been characterized by reward learning deficits linked to dysfunction in frontostriatal regions. Although initial behavioral evidence of reward learning deficits in rMDD has recently emerged, it is unclear whether these reflect impairments in neural reward processing that persist into remission. METHODS: We examined behavioral reward learning and 128-channel event-related potentials (ERP) during a well-validated probabilistic reward task in 26 rMDD individuals and 34 never-depressed controls. Temporo-spatial principal components analysis (PCA) was used to separate overlapping ERP components, and group differences in neural activity in a priori regions were examined using low-resolution electromagnetic tomography (LORETA). RESULTS: Individuals with rMDD displayed reduced behavioral reward learning, as well as blunted ERP amplitude to reward feedback. Importantly, the reduction in ERP amplitude occurred at a PCA factor that peaked during the time at which phasic reward feedback-related signaling - hypothesized to originate in the striatum and project to the anterior cingulate cortex (ACC) - are thought to modulate scalp-recorded activity. Consistent with this, LORETA analyses revealed reduced activity in the ACC in the rMDD group, and this blunting correlated with poorer reward learning. CONCLUSION: These findings suggest that the reward learning impairment observed in acute MDD persists into full remission and that these impairments may be attributable to abnormalities in the neural processes that support reward feedback monitoring, particularly within the ACC. PMID- 26858997 TI - A fluorescent nanoprobe for single bacterium tracking: functionalization of silver nanoparticles with tryptophan to probe the nanoparticle accumulation with single cell resolution. AB - The investigation of the interaction of silver nanoparticles and live bacteria cells is of particular importance for understanding and controlling their bactericidal properties. In this study, the process of internalization of silver nanoparticles in Escherichia coli cells was followed by means of synchrotron excitation deep ultraviolet (DUV) fluorescence imaging. Antimicrobial nanostructures that can absorb and emit light in the UV region were prepared by functionalization of silver nanoparticles with tryptophan amino acid and used as environmentally sensitive fluorescent probes. The nanostructures were characterized by morphological (TEM) and spectroscopic methods (UV-vis, FTIR, XPS, and photoluminescence). The TEM images and the analyses of the UV-vis spectra suggested that the addition of tryptophan led to the formation of hybrid nanostructures with pronounced eccentricity and larger sizes with respect to that of the initial silver nanoparticles. The DUV imaging showed that it was possible to distinguish the fluorescent signal pertaining to silver-tryptophan nanostructures from the autofluorescence of the bacteria. The spatial resolution of the fluorescence images was 154 nm which was sufficient to perform analyses of the accumulation of the nanostructures within a single bacterium. The DUV imaging results imply that the tryptophan-functionalized silver nanoparticles interact with cell membranes via insertion of the amino acid into the phospholipid bilayer and enter the cells. PMID- 26858999 TI - Ratiometric fluorescence sensor arrays based on quantum dots for detection of proteins. AB - Optical cross-reactive sensor arrays have recently been demonstrated as a powerful tool for high-throughput protein analysis. Nevertheless, applying this technology to protein detection is complicated by many external factors, such as the interfering substances, the background noise, and sample environmental changes in the biological matrix. Herein we demonstrate that a ratiometric fluorescence sensor array based on quantum dots can be employed to circumvent these limitations. Several intrinsic dual-emitting Mn-doped quantum dots capped with different organic functional groups were designed as sensing elements. Distinct and reproducible response patterns against the ratiometric sensor array were obtained from ten proteins in a buffer of different pH (pH 5.7, 7.4, and 8.3) and spiked into human urine. Linear discrimination analysis of the response patterns showed successful differentiation of the analytes at concentrations as low as 50 nM with high identification accuracy. Furthermore, this sensor system also enables the detection of these eight proteins (at 500 nM) in human urine without any treatment. The ratiometric fluorescence change from quantum dots for analysis of proteins can eliminate effectively the signal interference from the pH value change and the fluorescent background in human urine. The present study will open a new avenue to improve the discrimination ability of sensor arrays. PMID- 26858998 TI - Quantification of cortisol in human eccrine sweat by liquid chromatography - tandem mass spectrometry. AB - Cortisol has long been recognized as the "stress biomarker" in evaluating stress related disorders. Plasma, urine or saliva are the current source for cortisol analysis. The sampling of these biofluids is either invasive or has reliability problems that could lead to inaccurate results. Sweat has drawn increasing attention as a promising source for non-invasive stress analysis. A sensitive HPLC-MS/MS method was developed for the quantitation of cortisol ((11beta) 11,17,21-trihydroxypregn-4-ene-3,20-dione) in human eccrine sweat. At least one unknown isomer that has previously not been reported and could potentially interfere with quantification was separated from cortisol with mixed mode RP HPLC. Detection of cortisol was carried out using atmospheric pressure chemical ionization (APCI) and selected reaction monitoring (SRM) in positive ion mode, using cortisol-9,11,12,12-D4 as internal standard. LOD and LOQ were estimated to be 0.04 ng ml(-1) and 0.1 ng ml(-1), respectively. Linear range of 0.10-25.00 ng ml(-1) was obtained. Intraday precision (2.5%-9.7%) and accuracy (0.5%-2.1%), interday precision (12.3%-18.7%) and accuracy (7.1%-15.1%) were achieved. This method has been successfully applied to the cortisol analysis of human eccrine sweat samples. This is the first demonstration that HPLC-MS/MS can be used for the sensitive and highly specific determination of cortisol in human eccrine sweat in the presence of at least one isomer that has similar hydrophobicity as cortisol. This study demonstrated that human eccrine sweat could be used as a promising source for non-invasive assessment of stress biomarkers such as cortisol and other steroid hormones. PMID- 26859000 TI - Quantitative mass spectrometry imaging of small-molecule neurotransmitters in rat brain tissue sections using nanospray desorption electrospray ionization. AB - Small molecule neurotransmitters are essential for the function of the nervous system, and neurotransmitter imbalances are often connected to neurological disorders. The ability to quantify such imbalances is important to provide insights into the biochemical mechanisms underlying the disorder. This proof-of principle study presents online quantification of small molecule neurotransmitters, specifically acetylcholine, gamma-aminobutyric acid (GABA) and glutamate, in rat brain tissue sections using nanospray desorption electrospray ionization (nano-DESI) mass spectrometry imaging. By incorporating deuterated internal standards in the nano-DESI solvent we show identification, accurate mapping, and quantification of these small neurotransmitters in rat brain tissue without introducing any additional sample preparation steps. We find that GABA is about twice as abundant in the medial septum-diagonal band complex (MSDB) as in the cortex, while glutamate is about twice as abundant in the cortex as compared to the MSDB. The study shows that nano-DESI is well suited for imaging of small molecule neurotransmitters in health and disease. PMID- 26859001 TI - Immunoglobulin G4-positive plasma cell myeloma. PMID- 26859002 TI - Vitamin B12 deficiency presenting as pancytopenia with ring sideroblasts. PMID- 26859005 TI - SELF-ASSESSED DENTAL HEALTH KNOWLEDGE OF NIGERIAN DOCTORS. AB - OBJECTIVES: To assess medical doctors' knowledge of common dental diseases and the need to include dental education in the Nigerian undergraduate medical curriculum. DESIGN: Cross-sectional multicentre non-random survey using a convenience sample. SETTING: Tertiary hospitals across two geo-political zones of Nigeria. Participants were mostly recruited while attending seminars and other departmental events which brought doctors together. SUBJECTS: Medical doctors in tertiary hospitals across two geo-political zones of Nigeria. MAIN OUTCOME MEASURES: Knowledge of common dental diseases namely, dental caries, gingivitis and periodontitis was evaluated using an open-ended questionnaire. The definition, etiology, treatment and age-related risk were assessed. Exposure to dental education during undergraduate training was assessed. Opinion on desirability and suggested length of future training were also assessed. RESULTS: A total of 127 doctors (35 interns, 30 residents, 34 senior residents and 28 consultants) participated in the study. Overall, knowledge of definition, etiology, treatment and relative prevalence were recorded. About 69 doctors (54.3%) correctly defined dental caries, 120 (94.5%) correctly defined gingivitis while only only 29 (22.8%) correctly defined chronic periodontitis. The proportions of respondents who correctly identified disease etiology were 26 (20.5%) for caries, 31(24.4%) for gingivitis and 12 (9.4%) for chronic periodontitis. The proportions of respondents who correctly identified appropriate treatment modalities were 39 (30.7%) for caries, 18 (14.2%) for gingivitis and 6 (4.7%) for periodontitis. Those who correctly identified the relative, age-related prevalence of the three diseases were 81 (63.8%) for caries, 51 (40.2%) for gingivitis and 47 (37%) for periodontitis. CONCLUSION: Most of the medical doctors who participated in the study demonstrated inadequate knowledge of common dental diseases and about 97% of respondents supported the idea of including dental education into the current Nigerian undergraduate medical curriculum. PMID- 26859006 TI - CAPITATION IN HEALTHCARE FINANCING IN GHANA. AB - OBJECTIVE: To analyse implementation of the pilot study of the per capita system of healthcare financing in Ghana in 2012 for a determination of the likelihood of realising the inherent theoretical benefits when the system is rolled out nationally. DESIGN AND SETTING: First, publicly available information on how the pilot unfolded is presented, followed by the reaction of the health authorities to these developments. We then analysed accrued evidence on costs and developments vis-a-vis the theoretical benefits. RESULTS: It would appear that preparation for the pilot exercise could have been handled better. Concerns include i) the low level of both education and awareness of the capitation system among healthcare subscribers and primary care providers; ii) confusion about service provider to whom subscribers had been assigned for the capitation period; and iii) service providers not understanding differences between capitation financing and financing under the Ghana diagnostic Related Grouping; and iv) some indication of cost savings. CONCLUSION: Cost savings may be available nationally. This is important because cost containment is the driving force behind the introduction of the capitation system. PMID- 26859003 TI - In silico screening of the impact of hERG channel kinetic abnormalities on channel block and susceptibility to acquired long QT syndrome. AB - Accurate diagnosis of predisposition to long QT syndrome is crucial for reducing the risk of cardiac arrhythmias. In recent years, drug-induced provocative tests have proved useful to unmask some latent mutations linked to cardiac arrhythmias. In this study we expanded this concept by developing a prototype for a computational provocative screening test to reveal genetic predisposition to acquired long-QT syndrome (aLQTS). We developed a computational approach to reveal the pharmacological properties of I(Kr) blocking drugs that are most likely to cause aLQTS in the setting of subtle alterations in I(Kr) channel gating that would be expected to result from benign genetic variants.Weused themodel to predict themost potentially lethal combinations of kinetic anomalies and drug properties. In doing so, we also implicitly predicted ideal inverse therapeutic properties of K channel openers that would be expected to remedy a specific defect. We systematically performed "in silico mutagenesis" by altering discrete kinetic transition rates of the Fink et al. Markov model of human I(Kr) channels, corresponding to activation, inactivation, deactivation and recovery from inactivation of I(Kr) channels. We then screened and identified the properties of I(Kr) blockers that caused acquired long QT and therefore unmasked mutant phenotypes formild,moderate and severe variants. Mutant I(Kr) channels were incorporated into the O'Hara et al. human ventricular action potential (AP) model and subjected to simulated application of a wide variety of I(Kr)-drug interactions in order to identify the characteristics that selectively exacerbate the AP duration (APD) differences between wild-type and I(Kr) mutated cells. Our results show that drugs with disparate affinities to conformation states of the I(Kr) channel are key to amplify variants underlying susceptibility to acquired long QT syndrome, an effect that is especially pronounced at slow frequencies. Finally, we developed a mathematical formulation of the M54T MiRP1 latent mutation and simulated a provocative test. In this setting, application of dofetilide dramatically amplified the predicted QT interval duration in the M54T hMiRP1 mutation compared to wild-type. PMID- 26859007 TI - NEED FOR SCREENING FOR ALCOHOL AND DRUGS IN EMERGENCY TRAUMA UNITS. AB - OBJECTIVES: To examine the prevalence of alcohol and drug use and abuse, to identify socio-demographic characteristics that correlated with injury and to identify risk factors for injury in a Nigerian Trauma unit. DESIGN: Descriptive cross sectional study. SETTING: The study was carried out a general hospital trauma unit in Nigeria. SUBJECTS: One thousand one hundred and twenty one trauma patients and 303 controls. RESULTS: Of all injuries, 50.1% were road accidents, mean injury severity score was 41.3 SD (11.2), prevalence of alcohol abuse was 27.9%, cannabis abuse 14.0% and pretrauma alcohol use 41.2%, pre-trauma cannabis use was 6.9%. Multivariate analysis shows that age < 31 years 95% CI (0.26-0.89), alcohol abuse 95% CI (1.84-4.64), binge drinking in the previous 30 days 95% CI (1.76-6.46), cannabis abuse 95% CI (1.45-2.88) and pretrauma combined alcohol and cannabis use 95% CI (3.34-11.78) were risk factors for severe injury. CONCLUSION: Use and abuse of alcohol and drugs is highly prevalent among trauma patients seeking emergency care. Therefore trauma patients require routine toxicological screening to provide basis for preventive programmes or referrals for them. PMID- 26859008 TI - INJURY EXPERIENCE IN TANZANIA - NEED FOR INTERVENTION. AB - OBJECTIVE: To determine distribution of injuries and factors associated with mortality in six hospitals of Tanzania mainland. DESIGN: A Cross-Sectional hospital based study. SETTING: Data were collected from casualty departments of Muhimbili Orthopaedic Institute, Morogoro, Mtwara, Kigoma, Musoma regional hospitals and Korogwe district hospital. SUBJECTS: Patients who sustained injuries and attended in six involved hospitals between November 2011 and December 2012. RESULTS: Of the 9316 injury patients seen, 71.7% were males. Majority (55%) were between 18 - 45 years age group. Traffic crashes were the leading cause of injuries and accounted for 47.5% of all injuries. Fractures accounted for 49.2%, and injuries were severe in 1.2% as determinedby the Kampala trauma score II (KTS II). Majorities 66.7% were admitted and 2.4% died at the casualty. Factors associated with mortality were; being unemployed (P = 0.000), using ambulances to the hospital (P = 0.000), receiving medical attention within 2 to 10 hours after injury (P = 0.001), road traffic crashes (P = 0.000), 18-45 years age group (P = 0.003), low KTS II score (P = 0.000) and sustaining head injury (P = 0.000). CONCLUSION: Injuries in Tanzania are an important public health problem, predominantly in adult males, mostly due to traffic crashes. It is therefore important to reinforce preventive measures and pre-hospital emergency service is urgently needed. PMID- 26859009 TI - MASSIVE RECTORRHAGIA IN A RURAL HOSPITAL IN KENYA. AB - A young female patient presented to our hospital for massive rectorrhagia associated with clinical signs of peritonitis. The provisional diagnosis was of sigmoid volvolus, but laparatomy demonstrated that the problem originated from Pelvic Inflammatory Disease (PID). Despite prompt and uncomplicated surgery the patient did not survive, probably because of septicaemia or pulmonary embolism. PMID- 26859010 TI - PATTERN OF ANORECTAL MALFORMATIONS AND EARLY OUTCOMES OF MANAGEMENT AT MOI TEACHING AND REFERRAL HOSPITAL ELDORET-KENYA. AB - Objectives: To describe the anatomical sub-types of Anorectal malformations, their management and the early outcome at Moi Teaching and Referral Hospital (MTRH) over a 16 month period. Design: A prospective study. SETTING: MTRH, in the neonatal Unit and paediatric surgical wards for theinitial capture of patients and initial follow up. The Paediatric Surgical out-patient clinic was used for the subsequent follow ups. SUBJECTS: All infants diagnosed with ARM (Anorectal malformations) at MTRH from November 2011 to April 2013. MAIN OUTCOME MEASURES: Sub-types of the Anorectal malformations, coexisting abnormalities morbidity and mortality rates. RESULTS: There were 42 participants including 24 (57%) males and 18 (43%) females. Neonates presented at an average age of 4 +/- 3, three days and older children presented on average age of 152 +/- 118, three days. There were 30 (71%) neonates and 12 (29%) older infants. In males, the predominant sub-type was imperforate anus without a fistula found in ten participants (42% of males). In females, the predominant sub-type was recto-vestibular fistula found in 14 participants (78% of females). Mortality occurred in 13 (31%) participants among them ten (24%) had coexisting abnormalities. The main causes of morbidity were: colostomy complications in four (9.5%); wound,infections in one (5%); and wound dehiscence in one (5%). CONCLUSIONS: Patients with Anorectal malformations presented late at MTRH. The diagnosis at birth was missed in babies born at home as well as those delivered in health institutions. PMID- 26859011 TI - BLOOD TRANSFUSION IN CRITICALLY ILL PATIENTS IN AN INTENSIVE CARE UNIT OF A TERTIARY HOSPITAL IN NIGERIA. AB - OBJECTIVE: To evaluate the use of whole blood and blood products in our ICU to determine patterns and outcome after transfusion. DESIGN: A retrospective, case control study. SETTING: The Intensive care unit (ICU) of the University of Benin Teaching Hospital, a seven-bed open unit for the management of surgical, medical and paediatric patients. SUBJECTS: Patients who received blood transfusion in the ICU. Every patient who received blood transfusion was matched for a similar case without blood transfusion. Patients' socio-demographic characteristics, number of units of blood transfused, length of stay and outcomes were determined. RESULT: Approximately 30% of all patients admitted during the study period were transfused with blood. Majority of these patients (83.2%) had one to three units of blood. Obstetrics and neuro-surgical patients had more blood transfused than others. Whole blood constituted > 85% of blood transfused while packed cells and fresh frozen plasma constituted 11.8% and 2.8% respectively. Blood transfusion did not have any significant impact on patients' length of stay and mortality. The number of units of blood transfused appears to be associated with poor outcome (P = 0.006). CONCLUSION: Obstetric and neuro-surgical patients utilised blood and blood products in the ICU more than any other patients. The number of units of blood transfused was more predictive of mortality than the blood transfusion per se. A judicious use of blood and blood products, giving patients what they need and the development of transfusion guideline in the ICU is expedient. PMID- 26859012 TI - EFFICACY OF ANTIMICROBIAL ACTIVITY OF GARLIC EXTRACTS ON BACTERIAL PATHOGENS COMMONLY FOUND TO CONTAMINATE MEAT. AB - BACKGROUND: Meat is amajor source of food and raw materials for a number of industries, yet a lot of meat is wasted each year due to deterioration as a result of spoilage by microorganisms such as Pseudomonas, Acinetobacter, Moraxella, Bacillus, Campylobacter, Escherichia, Listeria, Clostridium, Salmonella and Staphylococcus species. OBJECTIVE: To determine efficacy of antimicrobial activity of garlic extracts on bacterial pathogens commonly found to contaminate meat. DESIGN: A cross sectional study. SETTING: The Department of Public Health, Pharmacology and Toxicology, Faculty of Veterinary Medicine University of Nairobi. SUBJECTS: Garlic from Nganoini farm in Laikipia County, Kenya. RESULTS: The results indicated that garlic absolute ethanol extract had the highest efficacy of antimicrobial activity inhibiting all test micro organisms. CONCLUSION: Ethanolic extract can be used as a meat preservative or decontaminant. PMID- 26859013 TI - THE EFFECT OF TWO LEVELS OF COUNSELLING ON ACCEPTANCE, UPTAKE AND EARLY OUTCOMES OF POST-PLACENTAL INTRA-UTERINE CONTRACEPTIVE DEVICE. AB - OBJECTIVE: To determine the effect of two levels of counselling on the provision of Intrauterine Contraceptive Device (IUCD) at six weeks post-partum of the post placental intrauterine device. SETTING: Embu Provincial General Hospital, Kenya. SUBJECTS: One hundred and thirty seven pregnant women at the gestation of 36 weeks to term, who attended Antenatal clinic and were followed until delivery and at six weeks post-partum. DESIGN: A randomised "open-label" clinical trial. RESULTS: One hundred and twenty seven study participants were enrolled and randomised to intensive (64 women) or routine FP counselling (63 women). Seventy eight per cent of women in the intensive FP counselled group and 66% in the routine FP counselled group accepted to have the post-placental IUCD inserted. There was no significant difference in uptake in the two-randomisation arms (p value 0.232). Complications included expulsion (3.7%), allergic reaction (1.8%), pelvic infection (1.8%) and abdominal pain (1.8%).The post-placental IUCD is a favourable method with continuation rates (91%), client (88%) and reported partner (77%) satisfaction were notably high at six weeks. The most critical barrier to uptake was lack of trained medical personnel to insert the post placental IUCD, which occurred in (60%) clients who had consented. CONCLUSION: The post-placental IUCD is an acceptable method among women irrespective of level of counselling. Intensive counselling did not significantly increase acceptance and uptake rates of post-placental IUCD insertion in comparison to routine counselling. PMID- 26859014 TI - THE UPTAKE OF MODERN CONTRACEPTIVES AMONG WOMEN OF REPRODUCTIVE AGE ATTENDING MATERNAL CHILD HEALTH AND FAMILY PLANNING (MCH/FP) CLINICS. AB - OBJECTIVE: To determine the uptake ana factors associated with the uptake of modern contraceptives among women of reproductive age (15-49 years) attending Maternal Child Health and Family Planning Clinics/Units in Rift Valley Provincial Hospital in Kenya. DESIGN: A descriptive cross-sectional study. SETTING: Rift Valley Provincial hospital which is a level five health facility situated in Nakuru County, Kenya. SUBJECTS: Women of reproductive age (15-49 years) who were attending Maternal Child Health and Family Planning Clinics at the Rift Valley Provincial Hospital. The respondents were identified by systematic random sampling RESULTS: Modern contraceptive uptake is over ninety percent (90.4, n = 218). The factors that are significantly associated with uptake of modern contraceptives are perceived convenience to use modern contraceptives (OR 0.39, CI: 0.16 - 0.93, p value- 0.04), experience of unmet needs of contraception (OR 0.08, CI: 0.03 - 0.2, p value- 0.001), history of a modern contraception discontinuation (OR 5.5, CI: 1.7 - 9.2, p value- 0.036) and knowledge of modern contraceptives (OR 19.1, CI: 12.3 - 27.5, p value-0.001). Conclusion: This study concluded that uptake of modern contraceptive is relatively high in Nakuru, Kenya and there is need for programmes to focus more on the client of modern contraceptive and the attributes of the modern contraceptives in up-scaling the uptake of modern contraceptives. PMID- 26859015 TI - COMPARATIVE STUDY ON THE LEVEL OF BACTERIOLOGICAL CONTAMINATION OF AUTOMATIC TELLER MACHINES, PUBLIC TOILETS AND PUBLIC TRANSPORT COMMERCIAL MOTORCYCLE CRASH HELMETS IN KIGALI CITY, RWANDA. AB - BACKGROUND: The environments can be contaminated by infectious agents that constitute a major health hazards as sources of community and hospital-acquired infections due to various activities. OBJECTIVE: A comparative study on the level of bacteriological contamination of automatic teller machines (ATMs), public toilets and commercial motorcycle crash helmets were conducted in Kigali city during the period of January to March, 2013. DESIGN: Samples were collected from selected ATMs, public toilets and commercial motorcycle crash helmets surfaces. Micro-organisms identified from these samples were associated to infecting organisms recovered from unwashed hands surfaces and recorded results in the nearby hospital. SETTING: Samples from each device and subject were transported to the laboratory where they were analysed for the presence of coliforms and other airborne, human skin and intestinal disease causing microorganisms. Microbiological methods including spread plate techniques and some biochemical tests were used to partially identify the microorganisms. SUBJECTS: Subjects involved in this study were consented students from University of Rwanda and Kigali motorcyclists for collections of samples from hands and crash helmets respectively. RESULTS: The following pathogenic bacteria have been found on the devices, Staphylococcus aureus, Staphylococcus epidermis, Streptococcus species, Escherichia coli, Salmonella, Klebsiella, Enterobacter aerogenes, Pseudomonas. The commercial motorcycle crash helmets had the highest level of bacteriological contamination compared to ATMs and public toilets. There was no growth observed on samples collected after treatment from ATMs, public toilets, and commercial motorcycle crash helmets. Attempt to correlate this finding with infecting organisms recovered from unwashed hands surfaces and recorded results in the nearby hospital show that the presences of some of these infectious pathogens. CONCLUSION: This study has revealed the ability of these public devices to serve as vehicle of transmission of microorganisms with serious health implications. To improve and ensure the safety of these public devices the use of disinfectants is of high importance on reducing bacteriological load on those public devices. Proper cleaning regimen to sanitise these facilities regularly and public education on their hygienic usage are recommended to reduce the associated risks. PMID- 26859016 TI - FUNCTIONAL BLINDNESS: INSURANCE FRAUD IN A CASE REPORT. AB - The insurance fraud is a known phenomenon and old in rich countries. The problem is relatively new in black Africa. Thanks to the installation of private companies and the emergence of social security fund, this phenomenon tends to grow without having precise figures. These frauds often involve the simulation of imaginary symptoms that primarily affect the five senses. The eye has a special place, its anatomical position easily exposed to work accident. Using simple clinical tests, the ophthalmologist must demonstrate that the patient with suspicion of visual loss is capable of normal vision and has no organic underlying deficit. This work aimed to report a case of insurance fraud by simulating a unilateral blindness following a work accident. PMID- 26859017 TI - THE CHALLENGES OF A PROSTATECTOMY IN RURAL AFRICA. AB - Delayed complications of an established surgical procedure like transvescical prostatectomy can occur in rural settings, where different factors can influence the outcome, beyond appropriate indication for surgery and technical skills of surgeons. Here we present a case that was per se surgically unremarkable, however a number of delayed omplications appeared in the post operative period, including infectious, neurologic, metabolic, hematologic ones, beyond purely post-surgery complications. PMID- 26859018 TI - CHILD AND MATERNAL ORAL HEALTHCARE: AN ASSESSMENT OF THE KNOWLEDGE OF NIGERIAN AND GHANAIAN NURSES. AB - OBJECTIVE: To ascertain and compare knowledge of child and maternal oral healthcare amongst a group of Nurses and Midwives in Ghana and Nigeria. DESIGN: A cross-sectional survey. SETTING: Health institutions in Cape Coast, Ghana and Port Harcourt, Nigeria. SUBJECTS: One hundred and sixty Nurses and Midwives (80 Ghanaians and 80 Nigerians). RESULTS: They had an age range of 21-65 years and a mean age of 37.8 (SD +/- 9.6) years. Majority of the Nurses in both countries indicated that women should brush their teeth with a toothbrush and toothpaste (92.1%), whilst the children should use salt and cotton wool twice daily. Although more of the Ghanaian Nurses (98.8%) considered routine dental visits to be important than the Nigerian population (80%), only 3.8% of the Ghanaian Nurses against 33.8% of the Nigerians indicated there was a connection between oral disease and delivery status. Opinions differed significantly as to the reason for the first dental visit with 65.4% of the Nigerian Nurses indicating this should be when the child has toothache whereas 51.9% of Ghanaian Nurses believed it is when the first tooth erupts. However, four to six years was the common choice for when self brushing should start in both countries. CONCLUSION: The knowledge of this group of Nurses and Midwives on maternal and child oral healthcare was insufficient. The Ghanaian Nurses had a better knowledge of preventive dental care than their Nigerian counterparts. PMID- 26859019 TI - SEQUENTIAL LOW COST INTERVENTIONS DOUBLE HAND HYGIENE RATES AMONG MEDICAL TEAMS IN A RESOURCE LIMITED SETTING. RESULTS OF A HAND HYGIENE QUALITY IMPROVEMENT PROJECT CONDUCTED AT UNIVERSITY TEACHING HOSPITAL OF KIGALI (CHUK), KIGALI, RWANDA. AB - OBJECTIVE: To assess the impact of multimodal low-cost interventions on hand hygiene practices among medical teams. DESIGN: A four week prospective observational study. SETTING: Medical wards of the University Teaching Hospital of Kigali (CHUK), Kigali, Rwanda. SUBJECTS: Medical teams comprising students, residents and consultant physicians. INTERVENTIONS: During week one, baseline hand sanitising rate (HSR)--the percentage of hand hygiene opportunities during which hands were sanitised- was recorded. On week two, alcohol based handrubs (ABHRs) were provided and placed strategically on every ward. For week three and four respectively, hand hygiene posters (HHPs) were placed at entry sites of each ward at eye level and subsequently at the head of each patient's bed. MAIN OUTCOME MEASURES: Post-intervention HSR was recorded weekly during morning ward rounds. The differences between pre-intervention and post-intervention HSRs as well as end-of-study pre- and post-contact HSR were assessed for significance using Pearson chi square test. RESULT: A total of 780 HHOs were covertly observed throughout the study. Baseline HSR was 24.8%. During week 2, there was a non significant increase in HSR (26.6% vs. 24.8%, p = 0.66). Overall, hand sanitising rates doubled from 24.8% to 50.6% following all study interventions (p < 0.001). There was a significant increase in post-patient contact and pre-patient contact HSRs with rates improving from 25.2% to 58% and 24.5% to 43% respectively (P < 0.01). CONCLUSION: Our study showed that low-cost interventions involving ensuring availability of ABHRs and posting HHPs significantly increased HSRs among medical teams but post-intervention rates were suboptimal. PMID- 26859020 TI - RANDOMISED DOUBLE BLIND STUDY TO COMPARE EFFECTIVENESS OF HONEY, SALBUTAMOL AND PLACEBO IN TREATMENT OF COUGH IN CHILDREN WITH COMMON COLD. AB - BACKGROUND: Acute upper respiratory infection is the most common childhood illness and presents with cough, coryza and fever. Available evidence suggests that cough medicines may be no more effective than honey-based cough remedies. OBJECTIVE: To compare effectiveness of honey, salbutamol and placebo in the treatment of cough in children with acute onset cough. DESIGN: Randomised control trial. SETTING: Aga Khan University Hospital Paediatric Casualty. SUBJECTS: Children between ages one to twelve years presenting with a common cold between December 2010 and February 2012 were enrolled. OUTCOME MEASURES: Frequency, severity and extent to which cough bothered and disturbed child and parental sleep were assessed at baseline and over the subsequent five days through telephone interview using a validated scoring tool. RESULTS: One hundred and forty five children were enrolled in the study (45- placebo, 57 -honey, 43 salbutamol). Of the 145 children 51% were male. Honey significantly reduced the total mean symptom score by day three (p < 0.001). Total mean difference in scores between day zero to five demonstrated a significant difference of honey's efficacy over placebo (p < 0.002) however no difference was noted when compared to salbutamol (p < 0.478). Significant differences in both total as well as each individual symptom score was detected with honey consistently scoring the best whilst placebo and salbutamol scored the worst. In paired comparisons honey was superior to placebo but not salbutamol, whilst salbutamol was not superior to placebo. CONCLUSION: Honey was most effective in symptomatic relief of symptoms associated with the common cold whilst salbutamol or placebo offered no benefit. PMID- 26859021 TI - RISK FACTORS AND SERO-PREVALENCE OF HEPATITIS B SURFACE ANTIGEN AMONG BLOOD DONORS IN UNIVERSITY OF ILORIN TEACHING HOSPITAL, ILORIN, NIGERIA. AB - BACKGROUND: Availability of safe blood and blood products for transfusion is increasingly difficult globally, especially in developing countries because of high prevalence of Transfusion Transmissible Infections. OBJECTIVES: To determine the prevalence of HBsAg among blood donors and to evaluate the socio-economic, demographic and medical factors associated with its infection. DESIGN: A prospective study. SUBJECTS: Three hundred and fifty consecutive blood donors were recruited. 2 ml of venous blood was collected aseptically from the ante cubital vein and subjected to serological test for HBsAg. RESULTS: High prevalence rate 10.9% was recorded. All the donors reactive to HBsAg were males (38,100%) with a mean age of 30.7 +/- 8.02 years, while 55.3%, 44.7%, 5.3%, 42%, 47.4%, 5.3% of them were single, married, primary school graduate, secondary school graduate, tertiary school graduate and illiterate respectively with 36.8%, 23.7%, 39.5% and 0% been unemployed, civil servants/professionals, skilled artisans and business/petty traders. The most common risk factor was multiple sexual partners 55.3%, followed by extra marital affairs 13.2%, tattooing 10.5%, previous blood transfusion 5.2%, previous surgery 2.6% and sex trading 2.6%. CONCLUSION: Active public enlightenment programmes and strict blood donation selection criteria need to be put in place in order to provide safe blood and blood products for transfusion. PMID- 26859022 TI - COAGULATION FACTORS LEVEL IN FRESH FROZEN PLASMA IN RWANDA. AB - Objectives: To determine the level of coagulation factors and inherited inhibitors in Fresh Frozen Plasma (FFP) and to evaluate Prothrombin Time and activated partial thrombin time in fresh frozen plasma. DESIGN: Cross-sectional study. SETTING: Jomo Kenyatta University of Agriculture and Technology in Medical Laboratory Sciences. SUBJECTS: Eighteen blood bags collected from voluntary blood donors. MAIN OUTCOME MEASURES: Coagulation factors and inhibitors levels, Prothrombin Time (PT) and Activated Partial thrombin Time (APTT) remained within the reference range requested by quality assurance regulations after three months of storage. RESULTS: APTT and PT show an increase from baseline to one month then remain constant up to three months, while, Fibrinogen, Factor II, Factor V, Factor VII, Factor X, Von Willbrand Factor, Protein C and Antithrombin decreased from baseline up to three months and then Factor VIII, Factor IX, Factor XI, Factor XII and Protein S, remained constant from baseline up to one month and decreased up to three months. CONCLUSION: There is good retention of all coagulation factors and inhibitors in plasma produced from whole blood within eight hours of collection, stored at minus 18 degrees C for three months. PMID- 26859023 TI - CUTANEOUS INVOLVEMENT OF HODGKIN LYMPHOMA IN A CHILD--CASE REPORT. AB - Specific cutaneous involvement in Hodgkin Lymphoma is rare and has not been reported in the younger paediatric age group. We report a case of a ten year old girl who presented with specific cutaneous involvement, confirmed using immunohistochemical stains. Treatment with combination chemotherapy resulted in rapid disappearance of the lesions and contrary to the generally poor prognosis associated with most other such reported cases in adults, she has clinically remained disease free two and a half years post treatment. Obtaining an accurate pathological diagnosis is essential to ensure appropriate treatment even in resource limited settings as illustrated by this case. PMID- 26859024 TI - PREVALENCE, CO-PREVALENCE AND RISK FACTORS OF PULMONARY PARAGONIMIASIS AND PULMONARY TUBERCULOSIS IN NIGERIAN CHILDREN IN THE NIGER DELTA AREA. AB - BACKGROUND: Nigeria has the highest burden of paragonimiasis in Africa and it is also among the high burden countries with tuberculosis. The true prevalence of these reemerging diseases is unknown in the country. OBJECTIVE: To determine the prevalence and co-prevalence of thesere-emerging diseases among children in a rural Nigerian community. DESIGN: Descriptive cross-sectional study. SETTING: Ewang, a rural fishing community in Mbo Local government Area of Akwa Ibom State, Nigeria. SUBJECTS: Primary and secondary school children aged 5-18years living in Ewang village, Mbo Local government Area of Akwa Ibom State, Nigeria. RESULTS: A total of 204 children were examined: 91(44.6%) were males, while 113(55.4%) were females. Ten of the subjects were sputum positive for paragonimus eggs, giving an overall prevalence rate of 4.9%,while six children were sputum positive for pulmonary tuberculosis with a prevalence rate of 2.9%. There was no case of co infection. The peak age prevalence of paragonimus ova-positive and Acid and Alcohol fast positive subjects was recorded in the five to nine year old age group with prevalence rate of 5.6% and7.4% respectively. There was a female preponderance among the paragonimus ova-positive subjects (90%) and the AAFB positive subjects (66.7%). CONCLUSIONS: The findings show that paragonimiasis is an emerging/re-emerging disease in southern Nigeria and further confirmed that the prevalence of tuberculosis is still on an upward rise. PMID- 26859025 TI - JOB SATISFACTION AND PSYCHOLOGICAL HEALTH OF MEDICAL DOCTORS IN CALABAR, SOUTHERN NIGERIA. AB - BACKGROUND: Employees should be happy at their work, considering the amount of time they devote to it throughout their working life. There is paucity of data on the job satisfaction and psychological health of medical doctors in Nigeria. OBJECTIVE: To assess the level of job satisfaction and its relationship to psychological health among medical doctors in a southern city of Nigeria. DESIGN: A cross-sectional descriptive survey. SETTING: Three major public hospitals in Calabar, Nigeria. SUBJECTS: Medical doctors who had worked for at least six months in the hospitals. RESULTS: Response rate was 73.0%. More than half (56.7%) of the respondents expressed overall satisfaction with their job. Inadequate pay and work overload were the most commonly mentioned reasons for job dissatisfaction. About a fifth of the respondents were at increased likelihood of psychological disorder. There was a statistically significant negative correlation between job satisfaction scores and GHQ scores. Satisfied respondents were least likely to have psychological disorder. CONCLUSION: Causes of job dissatisfaction among medical doctors should be addressed to improve their psychological health. PMID- 26859026 TI - EFFECTS OF ETHYLENE OXIDE RESTERILISATION AND IN-VITRO DEGRADATION ON MECHANICAL PROPERTIES OF PARTIALLY ABSORBABLE COMPOSITE HERNIA MESHES. AB - BACKGROUND: Prosthetic mesh repair for abdominal wall hernias is widely used because of its technical simplicity and low hernia recurrence rates. The most commonly used material is pure polypropylene mesh, however newer composite materials are recommended by some centers because of their advantages. However, these meshes are more expensive than pure polypropylene meshes. Resterilisation of a pure polypropylene mesh has been shown to be quite safe, and many centers prefer slicing a large mesh into smaller pieces that suitable for hernia type or defect size. Nevertheless there is no data about the safety after resterilisation of the composite meshes. OBJECTIVE: To search the effects of resterilisation and In vitro degradation in phosphate buffered saline solution on the physical structure and the mechanical properties of partially absorbable lightweigth meshes. DESIGN: Laboratory-based research. SUBJECTS: Two composite meshes were used in the study: One mesh is consisted of monofilament polypropylene and monofilament polyglecaprone--a copolymer of glycolide and epsilon (epsilon) caprolactone--(Ultrapro(r), 28 g/m2, Ethicon, Hamburg, Germany),andthe otherone consisted of multifilamentpolypropyleneandmultifilament polyglactine (Vypro II(r), 30 g/m2,Ethicon, Hamburg, Germany). Two large meshes were cut into rectangular specimens sized 50x20 mm for mechanical testing and 20x20 mm for In vitro degradation experiments. Meshes were divided into control group with no resterilisation and gas resterilisation. Ethylene oxide gas sterilisation was performed at 55 degrees C for 4.5 hours. In vitro degradation in 0.01 M phosphate buffered saline (PBS, pH 7.4) solution at 37 +/- 1 degrees C for 8 weeks was applied to one subgroup in each mesh group. Tensiometric measurements and scanning electron microscopyic evaluations were completed for control and resterilisation specimens. RESULTS: Regardless of resterilisation, when meshes were exposed to In vitro degradation, all mechanical parameters decreased significantly. Highest reduction in mechanical properties was observed for Ultrapro due to the degradation of absorbable polyglecaprone and polyglactin parts of these meshes. It was observed that resterilisation by ethylene oxide did not have significant difference on the degradation characteristics and almost similar physical structures were observed for resterilised and non-resterilised meshes. For Vypro II meshes, no significant mechanical difference was observedbetweenresterilised andnon-resterilised meshes after degradationwhile resterilised Ultrapro meshes exhibited stronger characteristics than non resterilised counterparts, after degradation. CONCLUSION: Resterilisation with ethylene oxide did not affect the mechanical properties of partially absorbable composite meshes. No important surface changeswere observed in scanning electron microscopy after resterilisation. PMID- 26859027 TI - PRESENCE OF CRYPTOCOCCUS SPECIES IN DOMESTIC CHICKEN (GALLUS GALLUS) DROPPINGS AND THE POSSIBLE RISK IT POSED TO HUMANS IN KABIGERIET VILLAGE, NAKURU COUNTY, KENYA. AB - OBJECTIVE: To isolate and identify Cryptococcus from domestic Chicken dropping. DESIGN: cross sectional study. SETTING: Kabigeriet village, Olenguorone Division, Nakuru county, approximately 282 km from Nairobi, Kenya. SUBJECTS: Sixty four domestic chicken droppings were sampled in thirty two homesteads after obtaining the farmers consent. RESULTS: Two species of Cryptococcus were isolated. CONCLUSION: Domestic chicken (Gallus gallus) harbor Pathogenic Cryptococcus in their dropping and their close proximity to human habitation poses a risk of AIDS to immunocompromised persons. PMID- 26859028 TI - FACTORS INFLUENCING ADHERENCE TO ARVS AMONG PATIENTS ATTENDING COMPREHENSIVE CARE CLINIC WITHIN JOMO KENYATTA UNIVERSITY OF AGRICULTURE AND TECHNOLOGY, KIAMBU COUNTY, KENYA. AB - BACKGROUND: The efficacy of anti-retroviral Therapy (ART) depends on adherence to the prescribed regimen. However, lack of adherence leads to treatment failure and drug resistance among other negative outcomes. OBJECTIVE: To determine factors influencing adherence to ARVS among patients attending the Comprehensive Care Clinic (CCC) within Jomo Kenyatta University of Agriculture and Technology (JKUAT). DESIGN: A descriptive cross sectional study. SETTING: Comprehensive Care Clinic within JKUAT. SUBJECTS: Three hundred HIV positive patients, undergoing ART treatment and follow up at the JKUAT clinic for a minimum duration of one month before the study, were recruited. RESULTS: Of the 300 patients enrolled for the study (70% females and 30% males), 81% were adhering to ARV treatment. The factors that were significantly associated with adherence included; Support (encouragement and reminder to take drugs) (P = 0.025); the number of meals respondents took in a day (P = 0.001); pill burden (P = 0.002) and forgetfulness (P = 0.001). However, there was no significant relationship between adherence and age, marital status, education, employment status or time taken to travel to the clinic. CONCLUSION: This study concluded that, the observed level of sub-optimal adherence to ART (19%) is of public health concern. These patients are vulnerable to treatment failure and development of resistant viral strains. Consequently the modifiable factors (Support, Number of meals taken, pill burden, and forgetfulness, should be addressed to change the current tread. PMID- 26859029 TI - SUITABILITY OF VITEK 2 SYSTEM IN IDENTIFICATION AND SUSCEPTIBILITY TESTING OF GRAM NEGATIVE BACTEREMIAS BY DIRECT INOCULATION. AB - OBJECTIVE: To verify the accuracy of direct Vitek testing for blood cultures with Gram-negative bacilli. DESIGN: Validation study. SETTING: Aga Khan University Hospital Nairobi. SUBJECTS: Twenty two positive blood cultures. MAIN OUTCOME MEASURES: Correct bacteria identification and errors for susceptibility testing. RESULTS: Of the 22 samples analysed 19 (86%) were correctly identified by direct Vitek testing and three (14%) were unidentified. Of the three, one had mixed growth and the other two had pure growth on sub-cultures. Of the 19 cultures with antimicrobial susceptibility testing by direct Vitek, three had discrepancies for some antibiotics when compared with the conventional Vitek method. These discrepancies were minor errors that would not have had any clinical impact. CONCLUSION: These data suggest that direct Vitek would provide acceptable identification and antimicrobial susceptibility testing results for Gram-negative bacilli. Compared to the standard method, the direct Vitek method would reduce turnaround time by at least twelve to twenty four hours. PMID- 26859030 TI - FUNCTIONAL MOTOR RECOVERY IN STROKE SURVIVORS-DETERMINANTS IN A SUB-SAHARAN AFRICAN STROKE UNIT. AB - OBJECTIVE: To find out the determinants of functional motor recovery in stroke survivors. DESIGN: A prospective cross-sectional study. SETTING: Stroke outpatient clinic tertiary care hospital. SUBJECTS: One hundred and two stroke survivors had their basic data captured as well as the modified Rankin score (both at the time of discharge after admission and at the time of evaluation in the clinic). RESULTS: Twenty nine (28.4%) had functional recovery versus 73 (71.6%) that did not. Younger age (OR = 0.95 {CI 0.90-0.99} P = 0.048), higher Rankin score at discharge (OR = 2.35 {CI 1.40-3.95} P = 0.001), fewer informal caregivers at home (OR = 0.68 {0.48-0.97} P = 0.034) and higher frequency of visits,to the physical therapist (OR = 1.30 {0.99-1.71} P = 0.05) predicted functional recovery. Age, modified Rankin score at discharge, duration between discharge from in-patient care and evaluation in clinic and frequency of visits to the physical therapist predicted group membership between functional recovery and others. CONCLUSION: In spite of the lean neurorehabilitation facilities in the setting of this study, increased frequency of visits to the physical therapist predicted functional recovery in stroke survivors as in more resource robust climates. It should therefore be prescribed until functional recovery is achieved. PMID- 26859031 TI - COMPARISON OF LOSARTAN AND ENALAPRIL EFFECTS ON RENAL FUNCTION IN HYPERTENSIVE ADULTS WITH CHRONIC KIDNEY DISEASE AT A KENYAN REFERRAL HOSPITAL. AB - OBJECTIVE: The objective of this study was to compare renal function in diabetic hypertensive chronic kidney disease patients receiving enalapril or losartan. DESIGN: This was a retrospective analytic cohort study. SETTING: Kenyatta National Hospital, Nairobi, Kenya. SUBJECTS: Two hundred adult patients with hypertension and diabetic nephropathy. INTERVENTIONS: One hundred and sixteen participants received an enalapril regimen while 84 were on a losartan regimen. MAIN OUTCOME MEASURES: Time to doubling of serum creatinine and changes in the levels of proteinuria. RESULTS: There was a higher risk of doubling of serum creatinine with losartan (Adjusted HR = 1.572; [95% CI: 1.015-2.434]; p = 0.043) than enalapril. There was a significant difference in time to doubling between the two arms--losartan 18 months, enalapril 36 month (p = 0.046). The changes in the levels of proteinuria between the two arms were not statistically significant for most of the follow up period except at the 15th month from treatment initiation (p = 0.05). CONCLUSIONS: Enalapril was found to be more reno protective compared to losartan. Where feasible, we suggest local use of enalapril as opposed to losartan for diabetic hypertensive chronic kidney disease patients. PMID- 26859032 TI - STARTING A LAPAROSCOPIC SURGERY PROGRAMME IN THE SECOND LARGEST TEACHING HOSPITAL IN GHANA. AB - BACKGROUND: Komfo Anokye Teaching Hospital (KATH) is the second largest hospital in Ghana. Two years have elapsed after performance of the first laparoscopic cholecystectomy. OBJECTIVES: To examine our experience and lessons learned. DESIGN: Retrospective review. SETTING: Komfo Anokye Teaching Hospital (KATH). SUBJECTS: We reviewed leadership support, the role of a surgeon champion, training of physician and OR staff, influence of surgeons from outside Ghana and equipment status. The results of laparoscopic cholecystectomies performed from 2010-2012 were compared with information available from open cholecystectomies over the same period. RESULTS: Evidence of leadership support included equipment purchase and invitation of outside experts yearly from 2008. A KATH surgeon champion was identified in 2010. A dedicated OR team received training and exhibited excellent ownership of equipment preparation. Since 2010, 25 laparoscopic cholecystectomies have been performed, 17 independently by a single surgeon. Average operative time was 1.41 hours and length of stay (LOS) 1.5 days. Conversion rate was 4.0% (1/25). Complication rate was 20.0% (5/25), none involving haemorrhage or injuries to bile ducts or bowel. Median patient satisfaction score was 5 on a scale of 1-5 where 5 is most satisfied. Complication rates and hospital stay were lower than for open cholecystectomy (20.0% vs 34.5%, p > 0.05 and 1.5 days vs 6.6 days, p < 0.001 respectively). Operative times were on average 27 min onger for laparoscopic cholecystectomy (p < 0.01). CONCLUSION: Laparoscopic cholecystectomy at KATH has become a reality with less complications rates, shorter LOS, and trends towards improved patient satisfaction. Expanding laparoscopic surgery in Ghana requires its inclusion into residency training programmes and public education about its benefits for both patients and physicians. PMID- 26859033 TI - PREDICTIVE ACCURACY OF TRANSCEREBELLAR DIAMETER IN COMPARISON WITH OTHER FOETAL BIOMETRIC PARAMETERS FOR GESTATIONAL AGE ESTIMATION AMONG PREGNANT NIGERIAN WOMEN. AB - OBJECTIVE: To compare the predictive accuracy of foetal trans-cerebellar diameter (TCD) with those of other biometric parameters in the estimation of gestational age (GA). DESIGN: A cross-sectional study. SETTING: The University of Benin Teaching Hospital, Nigeria. SUBJECTS: Four hundred and fifty healthy singleton pregnant women, between 14-42 weeks gestation. MAIN OUTCOME MEASURES: Trans cerebellar diameter (TCD), biparietal diameter (BPD), femur length (FL), abdominal circumference (AC) values across the gestational age range studied. Correlation and predictive values of TCD compared to those of other biometric parameters. RESULTS: The range of values for TCD was 11.9 - 59.7mm (mean = 34.2 +/- 14.1mm). TCD correlated more significantly with menstrual age compared with other biometric parameters (r = 0.984, p = 0.000). TCD had a higher predictive accuracy of 96.9% +/- 12 days), BPD (93.8% +/- 14.1 days). AC (92.7% +/- 15.3 days). CONCLUSION: TCD has a stronger predictive accuracy for gestational age compared to other routinely used foetal biometric parameters among Nigerian Africans. PMID- 26859034 TI - A FIVE YEAR REVIEW OF API20E BACTERIA IDENTIFICATION SYSTEM'S PERFORMANCE AT A TEACHING HOSPITAL. AB - OBJECTIVES: To assess the performance of the API20E bacteria identification system at a teaching hospital in Kenya. DESIGN: Retrospective study. SETTING: The microbiology laboratoryoratory of the Aga Khan University teaching Hospital. SUBJECTS: One thousand six hundred and fifty eight API20E records. MAIN OUTCOME MEASURES: The accuracy in identifying the bacteria species. RESULTS: One thousand four hundred and forty two (87.6%) isolates had the exact identity, 199 (12%) nearest identity, and seven (0.4%) no identity. The performance varied among the species; Acinetobacter baumanii had 140 (99.3%) isolates with the exact identity and only one (0.7%) with the nearest identity compared with Aeromonas hydrophila which had five (17.2%) with exact and 24 (82.8%) with nearest. CONCLUSIONS: The API20E system is a robust bacteria identification method which can serve small and medium clinical microbiology laboratories that may not afford automated systems. Adhering to the manufacturer's instructions and good. PMID- 26859035 TI - THE NEED FOR FAMILY MEETING IN THE MANAGEMENT OF PATIENTS ADMITTED INTO THE INTENSIVE CARE UNIT: EXPERIENCE FROM A TEACHING HOSPITAL IN NIGERIA. AB - OBJECTIVE: To evaluate the knowledge of family members of patients admitted into the Intensive Care Unit (ICU) in terms of their patients' clinical state, reasons for admission and progress of treatment. DESIGN: Prospective, cross-sectional study. SETTING: General Intensive Care Unit of the University of Benin Teaching Hospital, Benin City, Edo State, Nigeria. SUBJECTS: Twenty-five family members of patients admitted into the ICU were recruited. The data collected included socio demographic characteristics, level of education, awareness of the indications for ICU admission, expectations of outcome and level of satisfaction with family meeting. RESULTS: Fifty- six percent of family members claimed to be aware of the indication for admission into the ICU while 44% claimed ignorance. Only 24% of the family members who claimed to be aware were correct about the indication for admission. Among the participants, 36% were well informed about the prognosis of their patients' clinical condition. All the relatives interviewed were satisfied with the family meeting held with them. CONCLUSION: Majority of family members of critically ill patients were neither carried along in the management of their patients nor were they informed of likely outcome. A timely, well-planned and regular family meeting is therefore advocated in the management of critically ill patients. PMID- 26859036 TI - ROLES OF TRADITIONAL BIRTH ATTENDANTS AND PERCEPTIONS ON THE POLICY DISCOURAGING HOME DELIVERY IN COASTAL KENYA. AB - OBJECTIVES: To describe the roles of Traditional Birth Attendants (TBAs), to determine the perceptions of TBAs and Skilled Birth Attendants (SBAs) towards the policy discouraging home delivery by TBAs and to establish the working relationship between TBAs and SBAs in Kwale, Kenya. DESIGN: Community based cross sectional study. SETTING: Mwaluphamba, Kinango and Golini locations of Kwale County, Kenya. SUBJECTS: Fifty eight participants were involved in the study. Interviews were conducted with 22 TBAs and 8 SBAs as well as 3 FGDs with 28 TBAs were carried out in July 2012. MAIN OUTCOME MEASURES: Roles of TBAs, policy awareness and support as well as the working relationship between TBAs and SBAs. RESULTS: Before delivery, the main role of TBAs was checking position of the baby in the womb (86%) while during delivery, the main role was stomach massage (64%). However, majority (95%) of the TBAs did not provide any after delivery. All SBAs and 59% of TBAs were aware of the policy while 88% SBAs and 36% of TBAs supported it. The working relationship between TBAs and SBAs mainly involved the referral of women to health facilities (HFs). Sometimes, TBAs accompanied women to the HF offering emotional support until after delivery. CONCLUSION: TBAs in Kwale have a big role to play especially during pregnancy and delivery periods. Awareness and support of the policy as well as the collaboration between SBAs and TBAs should be enhanced in Kwale. PMID- 26859037 TI - ESTIMATED GLOMERULAR FILTRATION RATE AND RISK OF SURVIVAL IN ACUTE STROKE. AB - OBJECTIVE: To assess the risk of survival in acute stroke using the MDRD equation derived estimated glomerular filtration rate. DESIGN: A prospective observational cross-sectional study. SETTING: Medical wards of a tertiary care hospital. SUBJECTS: Eighty three acute stroke patients had GFR calculated within 48 hours of admission after basic data were captured. OUTCOME MEASURES: Stroke outcome was defined as either discharged or still-in-care (survived) or all cause in-hospital death. GFR was estimated by the MDRD equation, stroke severity was assessed by the Canadian Neurological Scale (CNS). Data were compared between the GFR groups of < 60 ml/min and >= 60 ml/min. Relative risks (RR) and odds ratios (OR) for stroke outcomes (survival and death) were estimated between the GFR groups and the homogeneity of the odds ratios among the different layers of stroke severity (CNS < 6.5 and >= 6.5) was determined by Breslow-Day and Tarone's test. Matanel Hazensel and Cochran's tests were used to determine conditional independence and the common odds ratio with stroke severity as a layering variable. RESULTS: No significant differences were found between the age and sex distribution of the two GFR groups. Serum urea and creatinine and CNS were significantly different between the GFR groups (p < 0.001, < 0.001, < 0.001). RR of survival and death for the GFR groups-less than 60 ml/min and above or equal to 60 ml/min were (0.425 and 1.204) and (2.360 and 0.830). The OR of survival for GFR below 60 ml/min compared to GFR above or equal to 60 ml/min was 0.353. There was homogeneity across the two layers of stroke severity (CNS score less than 6.5 and above or equal to 6.5), p = 0.612 and 0.612. CONCLUSION: Independent of stroke severity, GFR is a surrogate in the assessment of the risk of survival in acute stroke. PMID- 26859038 TI - ASSESSMENT OF NUTRITIONAL STATUS OF A GROUP OF HYPERTENSIVE PATIENTS ATTENDING TERTIARY HEALTHCARE FACILITIES IN NIGERIA. AB - BACKGROUND: Hypertension is a growing concern in developing and developed countries. Most of the diagnosed cases are caused by dietary lifestyle. OBJECTIVE: To assess the prevalence of overweight and obesity among adult hypertensive in a selected tertiary health care in Nigeria. DESIGN: A cross sectional study. SETTING: Lagos State University Teaching Hospital Ikeja, Lagos and University College Hospital, Ibadan Nigeria. SUBJECTS: A total of 120 patients (40.8% males and 59.2% females), volunteered to participate in the study after informed consent. Patients were recruited by convenience sampling method. OUTCOME MEASURES: Weight, height, waist and hip circumference, Body Mass Index (BMI) and Waist-Hip Ratio (WHR). RESULTS: The results showed that high percentage (62.5%) of the respondents had no family history of hypertension while 57.5% had hypertension less than one year ago. Patients' lifestyle revealed that 15.0% were taking alcohol, 85% had history of smoking tobacco while 53.8% of the respondents engaged in regular physical exercise. The BMI showed that grade 2 obesity was higher (41.0%) among females compared with males (21%). The WHR assessment also confirmed incidence of obesity among females compared to males as the WHR was 1.82 +/- 0.45 and 2.00 +/- 0.00 for male and female respectively. CONCLUSION: Nutrition screening of hypertension is necessary for early intervention against hypertension and obesity. PMID- 26859039 TI - ANAESTHESIA FOR OPHTHALMIC SURGICAL PROCEDURES. AB - BACKGROUND: Ophthalmic surgical procedures are performed under anaesthesia to enhance comfort and cooperation of patient. OBJECTIVE: To review factors influencing the choice of anaesthesia for ophthalmic surgical procedures. DESIGN: Restrospective descriptive study. SETTING: Eye unit of a tertiary hospital. SUBJECTS: All patients who had ophthalmic surgeries in the operating theatre from January 2002 to December 2009. RESULTS: Two hundred and ninety ophthalmic surgeries were carried out during the study period. Age range was 1-95 years and mean of 61.0 +/- 1.9; most (55%) were elderly while 4.8% were children. One hundred and fourty seven (50.7%) were males, 143(49.3%) females; male:female of 1.03:1. Local anaesthesia was the more commonly (92.1%) employed while general anaesthesia was used in 23(7.9%) patients. General anaesthesia was used more frequently (71.4%) in children compared to other age groups; the mean age and standard error of means for patients who had general anaesthesia (27.2 /5.4 years) is smaller compared to 63.9/0.93 years for patients who had local anaesthesia (p < 0.0001). Regional anaesthesia was the most frequently used for all types of procedures except for eye wall repairs in which general anaesthesia was used for 71.4% of patients (p < 0.0001). General anaesthesia was indicated in seven (41.2%) of emergency ophthalmic surgical procedures as compared to 16 (5.9%) of elective ophthalmic procedures P < 0.0001. CONCLUSION: General anaesthesia was more commonly employed in children, eye wall repairs and emergency ophthalmic surgical procedures. PMID- 26859041 TI - [HYGIENIC EVALUATION OF TERRITORIES OF FERGANA VALLEY RECREATIONAL AREAS]. AB - The article is devoted to hygienic monitoring ofrecreational areas of Fergana Valley. The aim is a hygienic evaluation of the Fergana Valley's (FV) mountain green areas on the basis of studies of heavy metals content in soil and indices of the anthropogenic load. The main contribution to the overall rate of chemical contamination of soils of the study areas was made by As, Zn, Cu and Ni, the average values of which exceed their respective PAC phytoaccumulation by 1.5-12 times. Out of studied 10 regions the one was classified as most permissible with the total allowable ratio of pollution in 13 relative units, the one--as dangerous (33 rel. units.) and eight regions were considered as moderately hazardous (18.2-27.2 rel. units). According to the degree of anthropogenic load seven studied FV areas were oppressed and three territories were classified as relatively prosperous. PMID- 26859040 TI - [The current problems of investigations into thanatogenesis and the causes of death considered in the articles published in the journal "Sudebno-meditsinskaya ekspertiza (Forensic Medical Expertise)" during the period from 2000 to 2014]. AB - The objective of the present work was the analysis of the scientometrical characteristics of the publication activity of the authors of the articles concerning the problems of investigations into thanatogenesis and the causes of death that were submitted for the publication in the journal "Sudebno meditsinskaya ekspertiza" during the period from 2000 to 2014. The analysis was aimed at detecting the priority fields of research of interest not only for domestic but especially for foreign specialists. The study has revealed the most popular Russian-language and foreign journals that were most frequently cited by the authors of "Sudebno-meditsinskaya ekspertiza". It was shown that the largest number of publications were submitted by the research groups affiliated with the departments and other subdivisions of the practical expert institutions of Moscow, Sankt-Petersburg, Astrakhan, Krasnodar, Baku, and Krasnoyarsk. It is concluded that the further analysis and assessment of the research activities of specialist in forensic medical expertise with the use of scientometrical methods constitute the indispensable condition for the development and improvement of the quality of forensic medical expertise in the Russian Federation. PMID- 26859042 TI - [The resolution of the Plenum of the Research Council on Human Ecology and Environmental Hygiene of the Russian Federation & Comprehensive impacts of environmental factors and lifestyle on the population's health: diagnostics, correction, prevention), city of Moscow, 11-12 December 2014]. PMID- 26859043 TI - [Academician of the RAS, MD, PhD, DSc, Professor G G Onishchenko (the 65th anniversary)]. PMID- 26859044 TI - [MD, PhD, DSc, Professor N V Shestopalov (the 65th anniversary)]. PMID- 26859045 TI - Na-alpha'-GeGaON Solid Solution Analogous to alpha'-SiAlON: Synthesis, Crystal Structure, and Potentiality as a Photocatalyst. AB - We demonstrated, for the first time, formation of the Na-alpha'-GeGaON (NamGe12 (m+n)Gam+nOnN16-n) solid solution, an analogue of the well-established alpha' SiAlON system. We successfully synthesized single-phase powder samples by reduction-nitridation of Na2CO3-GeO2-Ga2O3, in the solubility range of m ~ 0.8 1.7 with n ~ 0.2-0.3. The Rietveld refinement of powder X-ray diffraction data for Na-alpha'-GeGaON was conducted on the basis of the space group P31c of alpha' SiAlON, and the refinement converged with RB = 1.78% and RF = 1.02% for the composition of Na1.26(1)Ge10.50Ga1.50O0.24(1)N15.76(1), indicating reliably the isomorphism between the SiAlON and GeGaON systems. The results of (23)Na solid state nuclear magnetic resonance (NMR) spectroscopy clearly showed a single peak at the chemical shift of ~ 16 ppm, further proving the accommodation of Na in the alpha'-GeGaON matrix with the expected coordination environment. The synthesized Na-alpha'-GeGaON exhibited stable photocatalytic activity for the evolution of H2 from water under ultraviolet irradiation, which was comparable to that attained by beta-Ge3N4. PMID- 26859046 TI - Nanoscale Infrared, Thermal, and Mechanical Characterization of Telaprevir Polymer Miscibility in Amorphous Solid Dispersions Prepared by Solvent Evaporation. AB - Miscibility is of great interest for pharmaceutical systems, in particular, for amorphous solid dispersions, as phase separation can lead to a higher tendency to crystallize, resulting in a loss in solubility, decreased dissolution rate, and compromised bioavailability. The purpose of this study was to investigate the miscibility behavior of a model poorly water-soluble drug, telaprevir (TPV), with three different polymers using atomic force microscopy-based infrared, thermal, and mechanical analysis. Standard atomic force microscopy (AFM) imaging together with nanoscale infrared spectroscopy (AFM-IR), nanoscale thermal analysis (nanoTA), and Lorentz contact resonance (LCR) measurements were used to evaluate the miscibility behavior of TPV with three polymers, hydroxypropyl methylcellulose (HPMC), HPMC acetate succinate (HPMCAS), and poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA), at different drug to polymer ratios. Phase separation was observed with HPMC and PVPVA at drug loadings above 10%. For HPMCAS, a smaller miscibility gap was observed, with phase separation being observed at drug loadings higher than ~30-40%. The domain size of phase separated regions varied from below 50 nm to a few hundred nanometers. Localized infrared spectra, nano-TA measurements, images from AFM-based IR, and LCR measurements showed clear contrast between the continuous and discrete domains for these phase-separated systems, whereby the discrete domains were drug-rich. Fluorescence microscopy provided additional evidence for phase separation. These methods appear to be promising to evaluate miscibility in drug-polymer systems with similar Tgs and submicron domain sizes. Furthermore, such findings are of obvious importance in the context of contributing to a mechanistic understanding of amorphous solid dispersion phase behavior. PMID- 26859047 TI - Water Hydrogen-Bonding Network Structure and Dynamics at Phospholipid Multibilayer Surface: Femtosecond Mid-IR Pump-Probe Spectroscopy. AB - The water hydrogen-bonding network at a lipid bilayer surface is crucial to understanding membrane structures and its functional activities. With a phospholipid multibilayer mimicking a biological membrane, we study the temperature dependence of water hydrogen-bonding structure, distribution, and dynamics at a lipid multibilayer surface using femtosecond mid-IR pump-probe spectroscopy. We observe two distinguished vibrational lifetime components. The fast component (0.6 ps) is associated with water interacting with a phosphate part, whereas the slow component (1.9 ps) is with bulk-like choline-associated water. With increasing temperature, the vibrational lifetime of phosphate associated water remains constant though its relative fraction dramatically increases. The OD stretch vibrational lifetime of choline-bound water slows down in a sigmoidal fashion with respect to temperature, indicating a noticeable change of the water environment upon the phase transition. The water structure and dynamics are thus shown to be in quantitative correlation with the structural change of liquid multibilayer upon the gel-to-liquid crystal phase transition. PMID- 26859048 TI - A Low-Leakage Epitaxial High-kappa Gate Oxide for Germanium Metal-Oxide Semiconductor Devices. AB - Germanium (Ge)-based metal-oxide-semiconductor field-effect transistors are a promising candidate for high performance, low power electronics at the 7 nm technology node and beyond. However, the availability of high quality gate oxide/Ge interfaces that provide low leakage current density and equivalent oxide thickness (EOT), robust scalability, and acceptable interface state density (D(it)) has emerged as one of the most challenging hurdles in the development of such devices. Here we demonstrate and present detailed electrical characterization of a high-kappa epitaxial oxide gate stack based on crystalline SrHfO3 grown on Ge (001) by atomic layer deposition. Metal-oxide-Ge capacitor structures show extremely low gate leakage, small and scalable EOT, and good and reducible D(it). Detailed growth strategies and postgrowth annealing schemes are demonstrated to reduce Dit. The physical mechanisms behind these phenomena are studied and suggest approaches for further reduction of D(it). PMID- 26859049 TI - Correction to "Facile Fabrication of TiO2--Graphene Composite with Enhanced Photovoltaic and Photocatalytic Properties by Electrospinning". PMID- 26859051 TI - A note from the editor. PMID- 26859050 TI - Prologue: "First international conference on scientific data audit, policies and quality assurance". PMID- 26859052 TI - The credibility and legitimation of science: A loss of faith in the scientific narrative. AB - The presence of scientific misconduct challenges the authority of science to regulate itself. This paper examines the basis for scientific self-regulation, a basis which forms an ideology of science that has served to publicly legitimate the authority and autonomy of science. It is argued that the conventional scientific narrative overstates quality control and, as a consequence, that there is a potential crisis of legitimation in science. In particular, the dichotomy that is constructed between (1) the structure of science and (2) the individual scientist, is seen as problematic and cannot be used to shift the responsibility for misconduct onto individuals while at the same time preserving the sanctity of the structure of scientific practices-the two are inseparable. This analysis helps to locate the data audit/quality assurance movement and to clarify its role within the structure of scientific practices. The continued public support and legitimation of science requires that the scientific community critically examine and strengthen the structure of scientific practices. The re-examination should not focus overtly on controlling individual scientists. Rather, given the communal nature of science, the appropriate focus is on the social units that constitute and control the structure of scientific practices: laboratories, institutions, scientific societies and journals, and funding agencies. The First International Conference on Scientific Data Audit Policies and Quality Assurance should be viewed, then, as the beginning of a serious and difficult conversation among scientists on how to improve quality control in science and achieve public accountability while at the same time retaining the vitality of scientific practices. PMID- 26859053 TI - Data audit: Its place in auditing. AB - The terms "audit"; and "data audit"; have previously appeared in the science literature (see for example, Glide, 1975, p. 207, 1976, pp. 187-190; Noel, 1979, p. 73). Attempts have been made in that literature to discuss the nature of these terms. However, we are not aware of any discussions that have evaluated the nature of "data auditing"; in terms of the existing auditing literature. In this paper we briefly review the history of traditional auditing; briefly review the various types of auditing and auditors that exist in the United States; consider the generic nature of auditing; consider definitions of data audits that appear in existing science literature; consider the nature of data auditing; and consider where data auditing can be placed within auditing. PMID- 26859054 TI - The impact of funding on the formulation of research policy. AB - Using an accounting and political perspective, this paper explores how funding impacts on the formulation of research policy, through the governmental budgeting process and through the activity of corporate America, especially in the university arena. Initial discussion focuses on the public sector funding process, especially the concept of incrementalism in the budget process. Next, the political aspects of earmarking and pork-barreling are developed in the context of the university. Then, the relationships between government, corporate America and the university are briefly explored using a self-interest vs. public interest model. Finally, the university's research and education contribution to the process was shown in order to prove that the corporate-university relationship was not entirely unilateral in nature. This paper does not offer a "correct solution"; to the problems presented. It does present a number of important issues and divergent opinions concerning the funding of research and development and encourages further research into this highly volitile area. PMID- 26859055 TI - Public participation in data audits. AB - The United States in the early 1980s faced a crisis of confidence in the institutions that it had created to protect public health and the environment from the risks posed by toxic chemicals. Although the political climate of the times had a lot to do with the loss of public confidence in agencies like the Environmental Protection Agency (EPA), the Food and Drug Administration (FDA) and the Occupational Safety and Health Administration (OSHA), perhaps the most profound crack in the institutional edifice was the revelation that much (or at least some, depending upon whom you believed) of the scientific basis for past health and environmental decisions was grounded in invalid and even fraudulent health and safety studies. The IBT scandal (named after the Industrial Biotest Laboratories whose misadventures ultimately resulted in jail sentences for its officers) fueled accusations that the health and environmental agencies could not be trusted to reign in the chemical industry.(1) Public apprehensions were hardly quelled by the revelation in late 1982 that EPA had assigned only one full-time professional to audit the performance of all pesticide testing laboratories for evidence of additional fraud or misreporting.(2) It is fair to conclude that the recent trend toward establishing procedures for independent audits of health and safety data is a direct response to the crisis of public confidence resulting from the IBT scandal. Both EPA and FDA have promulgated "Good Laboratory Practice"; guidelines that serve as a baseline for such audits, and an increasing number of firms have established new "quality assurance"; controls to insure the agencies (and themselves) that the scientific underpinnings of health and safety decisions are sound. There is little reason to conclude, however, that this more or-less unilateral response to the IBT scandal will by itself stem public distrust in health and safety decisionmaking. Knowledgeable members of the public will not trust the agencies until they know that they can trust the audits, and they will not trust the audits until they begin to trust the auditors. This resurrects the ages-old conundrum: Who shall guard the guardians? Representatives of public interest groups, such as the Natural Resources Defense Council, Inc. and Ralph Nader's Public Citizen Health Research Group, have an easy answer to this question. They strongly believe that the only way to ensure the integrity of the scientific basis for health and safety decisionmaking is to spread all aspects of health and safety studies fully on the public record for all to see.(1) Representatives of the pharmaceutical and chemical industries, however, complain that this solution would expose valuable trade secrets to easy appropriation by unscrupulous competitors, thereby reducing industry incentives to develop new drugs and chemicals. Herein lies the core of a debate that has animated more than one congressional hearing and has reached all the way to the Supreme Court in recent years. This paper will examine the arguments for and against affording trade secrecy protection to health and safety testing data and apply those policies to the specific question of data audits. Finally, it will suggest a way to resolve the problem that enhances public trust in the audits while at the same time minimizing any disincentives to innovate. PMID- 26859056 TI - Financial auditing and fraud detection: Implications for scientific data audit. AB - This paper discusses some current issues and methods related to the detection of fraudulent financial reporting and draws potential implications for audit detection of fradulent scientific reporting. First, a brief history of auditor concern with fraud detection is presented. Then four issues are addressed: (1) How often does fraud occur? (2) What is fraud? (3) What are the general types of fraud? (4) How can auditors assess fraud risk and detect fraud? PMID- 26859057 TI - Data audit as a management tool. AB - Management faces the three basic challenges of achieving cost efficiency, successfully applying new technology, and minimizing risk. This paper examines the ways in which data audits can help managers come to terms with each of these challenges. It emphasizes the role of data audits in providing reliable information on which to base decisions and stresses the importance of auditing data in process rather than retrospectively. The paper examines frequently encountered sources of error and discusses the ways audits benefit management by assuring the integrity of experimental design, by preventing misassignment of observations, and by preventing the loss of data. PMID- 26859058 TI - On the potential cost effectiveness of scientific audits. AB - The rationale for the routine performance of scientific audits has been previously discussed, and it has been proposed that independent professionals audit scientific data just as certified public accountants in independent public accounting firms audit financial data (1-4). Scientific audits would typically require the examination of data in laboratory notebooks and other work sheets, upon which research publications are based. Examples of such audits have been publicized recently, although these represent audits which have been conducted relatively inefficiently, over periods of several years per audit, and which have only been conducted due to the persistence of whistleblowers suspecting scientific fraud (5, 6). A detailed report has also appeared on the results of an audit of the research activities of a particular individual, where the audit was limited solely to an examination of the research publications themselves for errors and discrepancies (7). It should be emphasized that the purpose of conducting scientific audits is not only to detect fabrication of experimental results but also to monitor presumably more prevalent, non-fraudulent, inappropriate practices, such as misrepresentation of data, inaccurate reporting, and departure from institutional guidelines for handling hazardous materials, working with human subjects, etc. Two concerns which have been raised concerning the performance of scientific audits relate to cost. What would they cost, and who would pay for them? These questions, however, may be turned around. What does it cost not to conduct such audits, and who pays for that? An assumption often made is that science is self-correcting, that sooner or later the truth will be revealed because of the need to replicate experiments of others for independent verification of novel findings (8). Testimony recently presented at a U.S. congressional hearing suggests that the self-correcting manner in which science advances represents a very slow and inefficient process for uncovering scientific fraud (5, 6, 9). Data from a survey of university scientists was also presented, indicating ". . . a reluctance to take prompt, corrective action not only when an investigator suspects another of misconduct but also should the investigator discover flaws in his or her own published reports-whether the flaws were the result of honest error or fraud"; (10). The uncritical acceptance by established scientists that the self-correcting process works compounds the problem. The Editor of Science has written that";. . . 99.9999 percent of reports are accurate and truthful. . ."; (8). If indeed only 0.0001% of published reports were inaccurate or untruthful, there would be little justification for scientific audits. However, congressional testimony from the National Institutes of Health (NIH) revealed that";. . . the NIH Director's office has handled an average of 15 20 allegations and reports of misconduct annually in its extramural programs, which supports the work of approximately 50,000 scientists"; (11). As I shall attempt to demonstrate, since NIH alone receives fraud-related complaints concerning the work of at least 0.03% of scientists it supports in other institutions, and since evidence indicates that the incidence of fraud is considerably greater than 0.03% (10, 12), the need to audit data is justifiable on the basis of being cost effective. PMID- 26859060 TI - Oxygenative and Dehydrogenative [3 + 3] Benzannulation Reactions of alpha,beta Unsaturated Aldehydes and gamma-Phosphonyl Crotonates Mediated by Air: Regioselective Synthesis of 4-Hydroxybiaryl-2-carboxylates. AB - Regioselective synthesis of 4-hydroxybiphenyl-2-carboxylates via the base mediated oxygenative [3 + 3] benzannulation reaction of alpha,beta-unsaturated aldehydes and gamma-phosphonyl crotonates is reported. A hydroxyl group is installed in the final product on the originally phosphorus-bound carbon via a novel oxygenative and dehydrogenative transformation. The reaction proceeds rapidly in an open flask, uses atmospheric oxygen as an oxidant, and affords good yields of substituted biaryl phenols. PMID- 26859061 TI - LactMed Update--An Introduction. PMID- 26859062 TI - Highly Selective Detection of 5-Methylcytosine in Genomic DNA Based on Asymmetric PCR and Specific DNA Damaging Reagents. AB - DNA methylation is a significant epigenetic modification of the genome that is involved in regulating many cellular processes. An increasing number of human diseases have been discovered to be associated with aberrant DNA methylation, and aberrant DNA methylation has been deemed to be a potential biomarker for diseases such as cancers. A safe, nontoxic, and sensitive method for accurate detection of 5-methylcytosine in genomic DNA is extremely useful for early diagnosis and therapy of cancers. In this paper, we established a novel system to detect 5 methylcytosine, which is based on bisulfite treatment, asymmetric PCR, and specific DNA damaging reagents. Our method could be used for identifying the loci of 5mC in genomic DNA and detecting the DNA methylation levels in tissues as well. PMID- 26859063 TI - The Major Soybean Allergen Gly m Bd 28K Induces Hypersensitivity Reactions in Mice Sensitized to Cow's Milk Proteins. AB - Reactions to soy have been reported in a proportion of patients with IgE-mediated cow's milk allergy (CMA). In this work, we analyzed if Gly m Bd 28K/P28, one of the major soybean allergens, is a cross-reactive allergen with cow milk proteins (CMP). We showed that P28 was recognized by IgE sera from CMA patients and activated human peripheral basophils degranulation. Moreover, IgE sera of mice exclusively sensitized to CMP recognized P28. Splenocytes from sensitized animals secreted IL-5 and IL-13 when incubated with CMP or soy proteins, but only IL-13 when treated with P28. In addition, a skin test was strongly positive for CMP and weakly positive for P28. Remarkably, milk-sensitized mice showed hypersensitivity symptoms following sublingual challenge with P28 or CMP. With the use of bioinformatics' tools seven putative cross-reactive epitopes were identified. In conclusion, using in vitro and in vivo tests we demonstrated that P28 is a novel cross-reactive allergen with CMP. PMID- 26859064 TI - Efficacy, safety, tolerability and population pharmacokinetics of tedizolid, a novel antibiotic, in Latino patients with acute bacterial skin and skin structure infections. AB - Acute bacterial skin and skin structure infections are caused mainly by Gram positive bacteria which are often treated with intravenous vancomycin, daptomycin, or linezolid, with potential step down to oral linezolid for outpatients. Tedizolid phosphate 200mg once daily treatment for six days demonstrated non-inferior efficacy, with a favourable safety profile, compared with linezolid 600mg twice daily treatment for 10 days in the Phase 3 ESTABLISH-1 and -2 trials. The objective of the current post-hoc analysis of the integrated dataset of ESTABLISH-1 and -2 was to evaluate the efficacy and safety of tedizolid (N=182) vs linezolid (N=171) in patients of Latino origin enrolled into these trials. The baseline demographic characteristics of Latino patients were similar between the two treatment groups. Tedizolid demonstrated comparable efficacy to linezolid at 48-72h in the intent-to-treat population (tedizolid: 80.2% vs linezolid: 81.9%). Sustained clinical success rates were comparable between tedizolid- and linezolid-treated Latino patients at end-of-therapy (tedizolid: 86.8% vs linezolid: 88.9%). Tedizolid phosphate treatment was well tolerated by Latino patients in the safety population with lower abnormal platelet counts at end-of-therapy (tedizolid: 3.4% vs linezolid: 11.3%, p=0.0120) and lower incidence of gastrointestinal adverse events (tedizolid: 16.5% vs linezolid: 23.5%). Population pharmacokinetic analysis suggested that estimated tedizolid exposure measures in Latino patients vs non-Latino patients were similar. These findings demonstrate that tedizolid phosphate 200mg, once daily treatment for six days was efficacious and well tolerated by patients of Latino origin, without warranting dose adjustment. PMID- 26859065 TI - Prevalence of rhinovirus in wheezing children: a comparison with respiratory syncytial virus wheezing. AB - OBJECTIVE: To explore the distribution and clinical manifestations of rhinovirus infection in wheezing children, and compare the clinical differences between rhinovirus- and respiratory syncytial virus-induced wheezing. MATERIALS AND METHODS: This prospective cohort study was carried out in Children's Hospital of Soochow University from Dec 2012 to Nov 2014. We enrolled consecutive hospitalized children <60 months of age presented with wheezing. Clinical data including cough, fever, dyspnea, crackles were recorded by pediatricians on the first day of admission. Meanwhile, nasopharyngeal aspirates were obtained to test for respiratory viruses, by using polymerase chain reaction method for rhinovirus, human bocavirus, and human metapneumovirus, and direct immunofluorescence assay to test for respiratory syncytial virus, adenovirus, parainfluenza virus types 1-3, and influenza virus types A and B. RESULTS: Rhinovirus was a main causative agent isolated in 14.7% of the hospitalized wheezing children in Suzhou, China, being second to respiratory syncytial virus (21.0%). Different from respiratory syncytial virus infection, which peaked in winter months, rhinovirus could be detected all year round, peaked between July and September, and in November. Children with rhinovirus infection were older and presented with more often allergic sensitizations, blood eosinophilia, and leukocytosis than those of respiratory syncytial virus infection. Logistic regression analysis revealed that rhinovirus-infected children experienced earlier wheezing more often than respiratory syncytial virus children (odds ratio, 3.441; 95% confidence interval, 1.187-9.979; p=0.023). CONCLUSION: Rhinovirus was a main viral pathogen in wheezing children, especially in summer time. Rhinovirus-induced wheezing was different from respiratory syncytial virus, apart from seasonal epidemics; these two groups differed with regard to age, allergic sensitizations, laboratory test, and history of wheezing episodes. PMID- 26859066 TI - The substantia nigra and ventral tegmental dopaminergic neurons from development to degeneration. AB - The pathology of Parkinson's disease (PD) is characterised by the loss of neurons in the substantia nigra parcompacta (A9), which results in the insufficient release of dopamine, and the appearance of motor symptoms. Not all neurons in the A9 subregions degenerate in PD, and the dopaminergic (DA) neurons located in the neighboring ventral tegmental area (A10) are relatively resistant to PD pathogenesis. An increasing number of quantitative studies using human tissue samples of these brain regions have revealed important biological differences. In this review, we first describe current knowledge on the multi-segmental neuromere origin of these DA neurons. We then compare the continued transcription factor and protein expression profile and morphological differences distinguishing subregions within the A9 substantia nigra, and between A9 and A10 DA neurons. We conclude that the expression of three types of factors and proteins contributes to the diversity observed in these DA neurons and potentially to their differential vulnerability to PD. In particular, the specific axonal structure of A9 neurons and the way A9 neurons maintain their DA usage makes them easily exposed to energy deficits, calcium overload and oxidative stress, all contributing to their decreased survival in PD. We highlight knowledge gaps in our understanding of the cellular biomarkers for and their different functions in DA neurons, knowledge which may assist to identify underpinning disease mechansims that could be targeted for the treatment of any subregional dysfunction and loss of these DA neurons. PMID- 26859070 TI - Synthesis, antiproliferative activities, and computational evaluation of novel isocoumarin and 3,4-dihydroisocoumarin derivatives. AB - A series of novel isocoumarin derivatives were synthesized using Castro-Stephens cross-coupling. Moreover, novel 3,4-dihydroisocoumarin derivatives were obtained by catalytic hydrogenation of the corresponding isocoumarin precursors. The antiproliferative activity of all compounds was evaluated in vitro in different tumor cells. Furthermore, docking calculations were performed for the kallikrein 5 (KLK5) active site to predict the possible mechanism of action of this series of compounds. Theoretical findings indicate that the 3,4-dihydroisocoumarin derivative 10a forms hydrogen bonds with Ser190 and Gln192 residues of KLK5. This derivative was the most active compound in the series with potent antiproliferative activity and high selectivity index (SI > 378.79) against breast cancer cells (MCF-7, GI50 = 0.66 MUg mL(-1)). This compound represents a promising matrix for developing new antiproliferative agents. PMID- 26859071 TI - Synthesis and in vitro antitumour activity of tiazofurin analogues with nitrogen functionalities at the C-2' position. AB - Synthesis of three tiazofurin (1) isosteres with nitrogen functionalities at the C-2' position (N3, NH2 and NH3(+)Cl(-)) has been achieved, in multistep sequences, starting from monoacetone d-glucose. A number of potential bioisosteres of 1 bearing acylamido functions at the C-2' position have also been synthesized from the same sugar precursor. In vitro cytotoxicities of target molecules against a number of human tumour cell lines were recorded and compared with those observed for lead molecule 1. Some of the synthesized compounds showed potent in vitro antitumour activity, such as 2'-azido derivative 2, which is the most potent of all molecules under evaluation (IC50 0.004 MUM against MCF-7 cells). Flow cytometry data suggest that cytotoxic effects of these compounds in the culture of K562 cells might be mediated by apoptosis, additionally revealing that these molecules induced changes in cell cycle distribution of these cells. Results of Western blot analysis indicate that the synthesized tiazofurin analogues induce apoptosis in a caspase-dependent way. PMID- 26859072 TI - Emotional Distress in the Partners of Type 1 Diabetes Adults: Worries About Hypoglycemia and Other Key Concerns. AB - BACKGROUND: Although the widespread prevalence of diabetes-related distress (DD) in adults with type 1 diabetes (T1D) has been well established, there has been little inquiry into the experiences of their spouse/partners. Therefore the goal of this study was to investigate the prevalence and sources of DD in the spouses and partners of adults with T1D ("T1D partner") and to examine the associations of DD in this population with key demographic and contextual factors. MATERIALS AND METHODS: Qualitative interviews with 11 T1D partners led to the development of 44 DD survey items, which were examined by exploratory factor analysis (EFA). Regression models examined associations of the resulting DD scales with four groups of variables: partner demographics and contextual variables, as well as person with diabetes (PWD) demographics, diabetes status, and behavioral factors. RESULTS: EFA with 317 T1D partners yielded a 22-item scale with four factors: Hypoglycemia Distress, Emotional Distress, Management Distress, and Role Distress. All scales were significantly correlated with the three criterion variables (depression, general life stress, and diabetes-related relationship satisfaction), suggesting satisfactory concurrent validity. High DD was most common for Hypoglycemic Distress (64.4% of the sample) and least common for Management Distress (28.4%). Greater DD was significantly and independently linked with being younger, female, greater involvement in the PWD's diabetes management, lower levels of relationship satisfaction, less trusting of the PWD's physician, poorer PWD glycemic control, and more frequent hypoglycemic episodes. T1D partners also reported low levels of diabetes-related support from all sources. CONCLUSIONS: Four sources of partner DD were identified. Results suggest that DD in T1D partners is common, especially distress associated with hypoglycemia. Predictors of T1D partner DD come from multiple sources: demographic, disease-related, and contextual arenas, all pointing to opportunities for acknowledging and addressing DD directly in this population. PMID- 26859073 TI - Changes in mood stabilizer prescription patterns in bipolar disorder. AB - BACKGROUND: Lithium is a first line treatment option in bipolar disorder, but several alternative treatments have been introduced in recent years, such as antiepileptic and atypical antipsychotic drugs. Little is known about how this has changed the prescription patterns. We investigated possible changes in the use of mood stabilizers and antidepressants in Sweden during 2007-2013. METHODS: Data was collected from Swedish registers: the National Quality Assurance Register for bipolar disorder (BipolaR), the Prescribed Drug Register, and the Patient Register. Logistic regression models with drug use as outcomes were used to adjust for confounding factors such as sex, age, year of registration, and subtypes of bipolar disorder. RESULTS: In both bipolar subtypes, lithium use decreased steadily during the study period, while the use of lamotrigine and quetiapine increased. The use of valproate decreased in bipolar II disorder and the use of olanzapine decreased among women. The use of antidepressant remained principally unchanged but increased somewhat in bipolar I disorder. LIMITATIONS: We only report data from 2007 as the coverage of BipolaR prior to 2007 was too low to allow for reliable analyses. CONCLUSION: Significant changes in the prescription of drugs in the treatment of bipolar disorder have occurred in recent years in Sweden. Further studies are needed to clarify whether these changes alter the outcome in bipolar disorder. PMID- 26859074 TI - Gaq signaling is required for the maintenance of MLL-AF9-induced acute myeloid leukemia. PMID- 26859075 TI - Lysosomotropic agents selectively target chronic lymphocytic leukemia cells due to altered sphingolipid metabolism. AB - Lysosome membrane permeabilization (LMP) mediates cell death in a variety of cancer cells. However, little is known about lysosomes and LMP in chronic lymphocytic leukemia (CLL). Owing to drug resistance and toxicity in CLL patients, better treatment strategies are required. Our results show that CLL cells were sensitive to the lysosomotropic agent siramesine. Furthermore, this drug was more effective in CLL cells, regardless of prognostic factors, compared with normal B cells. Siramesine caused LMP, lipid peroxidation and transcription factor EB nuclear translocation followed by mitochondrial membrane potential loss and reactive oxygen species release. Siramesine-induced cell death was blocked by lipid antioxidants, but not by soluble antioxidants or protease inhibitors. To determine whether CLL cells had altered lysosomes, we investigated sphingolipid metabolism as the lysosome is a hub for lipid metabolism. We found that CLL cells had more lysosomes, increased sphingosine-1-phosphate phosphatase 1 (SPP1) expression, and increased levels of sphingosine compared with normal B cells. Raising sphingosine levels increased LMP and cell death in CLL cells, but not in normal B cells. Together, these results show that excess sphingosine in CLL cells could contribute to their sensitivity toward LMP. Thus, targeting the lysosome could be a novel therapeutic strategy in CLL. PMID- 26859077 TI - The landscape of myeloid neoplasms with isochromosome 17q discloses a specific mutation profile and is characterized by an accumulation of prognostically adverse molecular markers. PMID- 26859078 TI - Identification of MYC mutations in acute myeloid leukemias with NUP98-NSD1 translocations. PMID- 26859076 TI - Secondary malignancies in chronic myeloid leukemia patients after imatinib-based treatment: long-term observation in CML Study IV. AB - Treatment of chronic myeloid leukemia (CML) has been profoundly improved by the introduction of tyrosine kinase inhibitors (TKIs). Long-term survival with imatinib is excellent with a 8-year survival rate of ~88%. Long-term toxicity of TKI treatment, especially carcinogenicity, has become a concern. We analyzed data of the CML study IV for the development of secondary malignancies. In total, 67 secondary malignancies were found in 64 of 1525 CML patients in chronic phase treated with TKI (n=61) and interferon-alpha only (n=3). The most common malignancies (n?4) were prostate, colorectal and lung cancer, non-Hodgkin's lymphoma (NHL), malignant melanoma, non-melanoma skin tumors and breast cancer. The standardized incidence ratio (SIR) for all malignancies excluding non melanoma skin tumors was 0.88 (95% confidence interval (0.63-1.20)) for men and 1.06 (95% CI 0.69-1.55) for women. SIRs were between 0.49 (95% CI 0.13-1.34) for colorectal cancer in men and 4.29 (95% CI 1.09-11.66) for NHL in women. The SIR for NHL was significantly increased for men and women. An increase in the incidence of secondary malignancies could not be ascertained. The increased SIR for NHL has to be considered and long-term follow-up of CML patients is warranted, as the rate of secondary malignancies may increase over time. PMID- 26859079 TI - The possible perils of targeted therapy. PMID- 26859082 TI - How does dementia onset in parents influence unmarried adult children's wealth. AB - There is a growing concern that long-term care (LTC) needs of older adults lead to negative financial consequences for their family members. This paper examines whether the onset of dementia in parents influences wealth change among unmarried adult children regardless of their status as informal caregivers. Longitudinal data from seven waves (1998-2010) of the Health and Retirement Study (1540 person wave observations) are used to analyze this question. Unconditional quantile regressions demonstrate that as a result of parental dementia diagnosis, unmarried adult children have lower wealth accumulation above the median of the wealth change distribution. These effects are more pronounced for unmarried adult children without siblings. Further, this response is observed to persist in the subsequent period as well. Both losses in labor income and nursing home expenditures may play a role in leading to wealth declines. PMID- 26859080 TI - Targeting vasculogenesis to prevent progression in multiple myeloma. AB - The role of endothelial progenitor cell (EPC)-mediated vasculogenesis in hematological malignancies is not well explored. Here, we showed that EPCs are mobilized from the bone marrow (BM) to the peripheral blood at early stages of multiple myeloma (MM); and recruited to MM cell-colonized BM niches. Using EPC defective ID1+/- ID3-/- mice, we found that MM tumor progression is dependent on EPC trafficking. By performing RNA-sequencing studies, we confirmed that endothelial cells can enhance proliferation and favor cell-cycle progression only in MM clones that are smoldering-like and have dependency on endothelial cells for tumor growth. We further confirmed that angiogenic dependency occurs early and not late during tumor progression in MM. By using a VEGFR2 antibody with anti vasculogenic activity, we demonstrated that early targeting of EPCs delays tumor progression, while using the same agent at late stages of tumor progression is ineffective. Thus, although there is significant angiogenesis in myeloma, the dependency of the tumor cells on EPCs and vasculogenesis may actually precede this step. Manipulating vasculogenesis at an early stage of disease may be examined in clinical trials in patients with smoldering MM, and other hematological malignancies with precursor conditions. PMID- 26859083 TI - Imaging biomarkers in ovarian cancer: the role of 18F-FDG PET/CT. AB - Ovarian cancer represents one of the major form of cancer in women in the western world and its silent nature leads to a late clinical manifestation at advanced stage in many patients. Therefore the role of imaging techniques is very important for the correct management of these patients. In the present review, the role of 18F-FDG-PET/CT in the different clinical settings is presented and a comparison with other imaging modalities and serum biomarker CA-125 are discussed. PMID- 26859084 TI - New radiotracers in gynecological cancer: beyond 18F-FDG. AB - Imaging plays an important role in the management of gynecological cancers. There is a clinical need for noninvasive prognostic biomarkers to provide more detailed tumor characterization at the baseline and/or early during therapy, which may potentially improve outcomes and enable a personalized treatment approach. Imaging parameters derived from PET/CT techniques are emerging as promising imaging biomarkers. This review details the current evidence and future potential of functional imaging using non-2-deoxy-2-[18F]fluoro-D-glucose (FDG) tracers in gynecological cancers. PMID- 26859081 TI - Increasing intensity of therapies assigned at diagnosis does not improve survival of adults with acute myeloid leukemia. AB - We randomized 3375 adults with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome to test whether increasingly intensive chemotherapies assigned at study-entry and analyzed on an intent-to-treat basis improved outcomes. In total, 1529 subjects <60 years were randomized to receive: (1) a first course of induction therapy with high-dose cytarabine and mitoxantrone (HAM) or with standard-dose cytarabine, daunorubicin and 6 thioguanine (TAD) followed by a second course of HAM; (2) granulocyte-colony stimulating factor (G-CSF) or no G-CSF before induction and consolidation courses; and (3) high-dose therapy and an autotransplant or maintenance chemotherapy. In total, 1846 subjects ?60 years were randomized to receive: (1) a first induction course of HAM or TAD and second induction course of HAM (if they had bone marrow blasts ?5% after the first course); and (2) G-CSF or no G-CSF as above. Median follow-up was 7.4 years (range, 1 day to 14.7 years). Five-year event-free survivals (EFSs) for subjects receiving a first induction course of HAM vs TAD were 17% (95% confidence interval, 15, 18%) vs 16% (95% confidence interval 14, 18%; P=0.719). Five-year EFSs for subjects randomized to receive or not receive G-CSF were 19% (95% confidence interval 16, 21%) vs 16% (95% confidence interval 14, 19%; P=0.266). Five-year relapse-free survivals (RFSs) for subjects <60 years receiving an autotransplant vs maintenance therapy were 43% (95% confidence interval 40, 47%) vs 40 (95% confidence interval 35, 44%; P=0.535). Many subjects never achieved pre-specified landmarks and consequently did not receive their assigned therapies. These data indicate the limited impact of more intensive therapies on outcomes of adults with AML. Moreover, none of the more intensive therapies we tested improved 5-year EFS, RFS or any other outcomes. PMID- 26859085 TI - Molecular imaging in cervical cancer. AB - Despite the development of screening and of a vaccine, cervix cancer is a major cause of cancer death in young women worldwide. A third of women treated for the disease will recur, almost inevitably leading to death. Functional imaging has the potential to stratify patients at higher risk of poor response or relapse by improved delineation of disease extent and tumor characteristics. A number of molecular imaging biomarkers have been shown to predict outcome at baseline and/or early during therapy in cervical cancer. In future this could help tailor the treatment plan which could include selection of patients for close follow up, adjuvant therapy or trial entry for novel agents or adaptive clinical trials. The use of molecular imaging techniques, FDG PET/CT and functional MRI, in staging and response assessment of cervical cancer is reviewed. PMID- 26859086 TI - Peroxide Natural Products from Plakortis zyggompha and the Sponge Association Plakortis halichondrioides-Xestospongia deweerdtae: Antifungal Activity against Cryptococcus gattii. AB - Cryptococcus gattii is a human pathogen and causative agent of a pernicious, sometimes fatal, disseminated fungal disease. Investigation of antifungal extracts of the marine sponge association Plakortis halichondrioides-Xestospongia deweerdtae and the sponge Plakortis zyggompha from the Bahamas led to the discovery and isolation of 6-epi-7,8-dihydroplakortide K (1), plakortide AA (2), and three new plakinic acids, N-P (4-6; unstable 1,2-dioxolanes bearing benzyl substituted conjugated dienes), along with known plakinic acids L, K, and M.5 Chiroptical comparisons and DFT calculations of (13)C NMR chemical shifts were used to assign the absolute stereostructure of 4. The stereospecific base promoted rearrangement-saponification of 1 to 10 was briefly investigated and showed tight kinetic control and stereospecific formation of the new C-2 stereocenter with inversion at C-3. Plakinic acid M and plakortides 9 and 11 exhibited antifungal activity against C. gattii (MIC90 = 2.4 to 36 MUM), but plakinic acids N-P were inactive under the same conditions. PMID- 26859087 TI - The ABCs (and Ds) of Bone Imaging in Children With Crohn Disease. PMID- 26859088 TI - Do We Really Need Soap to Clean the Rectum? PMID- 26859089 TI - Time for Personalized Biologic Therapy: One Size Does Not Fit All. PMID- 26859090 TI - Antroduodenal Manometry Is Abnormal in Children Presenting With Orthostatic Intolerance and Gastrointestinal Symptoms. AB - OBJECTIVES: Gastrointestinal (GI) symptoms of nausea, vomiting, and abdominal pain are common in patients with orthostatic intolerance (OI), including neurally mediated hypotension (NMH) and postural orthostatic tachycardia syndrome (POTS). Autonomic dysregulation is considered the underlying pathophysiology behind the cardiovascular symptoms of POTS. Because the autonomic nervous system also regulates GI motility, we hypothesized that patients with POTS and GI symptoms will have evidence of autonomic dysmotility of the upper GI tract. METHODS: Thirty-five subjects with OI and GI symptoms were studied. All the subjects had a 24-hour antroduodenal manometry (ADM) study, in conjunction with pharmacologic challenge and autonomic and tilt table testing (TTT). RESULTS: The mean subject age was 16.2 +/- 2.8 years (range 10-23.8 years), and male to female ratio was 10:25. TTT was abnormal in all the 35 subjects, whereas Valsalva testing was abnormal (+40 mmHG) in 21 of 34 (62%) subjects, and corrected QT interval was >=0.44 seconds in 19 of 35 (54%) subjects. During TTT, GI symptoms were reproduced in 31 of 35 (89%) studies. ADM was found to be abnormal at baseline, before the TTT in 5 of 35 (14%) subjects, whereas it became abnormal in 23 of 34 (68%) subjects during TTT. In addition, the expected response to the pharmacologic challenge was limited. Overall, ADM was abnormal in 26 of 35 (74%) patients either at baseline or during TTT in these subjects with OI. CONCLUSIONS: ADM is frequently abnormal in children with OI and GI symptoms. Upper GI motility studies should be a part of the comprehensive evaluation in this population. PMID- 26859091 TI - Neurodevelopment of Preterm Infants at 24 Months After Neonatal Supplementation of a Prebiotic Mix: A Randomized Trial. AB - OBJECTIVES: Fetal brain maturation is disrupted by preterm birth. Inflammation during the neonatal period may further harm neurodevelopmental outcomes. The present study aimed to determine the effect of short-chain galacto oligosaccharides/long-chain fructo-oligosaccharides/pectin-derived acidic oligosaccharides (scGOS/lcFOS/pAOS) on neurodevelopmental outcomes measured by Bayley Scales of Infant and Toddler Development in preterm infants at 24 months. METHODS: In this randomized controlled trial, scGOS/lcFOS/pAOS or placebo was supplemented between days 3 and 30 of life. Serum samples at day 1, 7, and 14 were analyzed for cytokine levels. Stool samples at day 1, 7, 14, and 30 were measured for bacterial count and bifidobacteria percentage. At 24 months corrected age infants were followed up by a blinded pediatric psychologist for the Bayley Scales of Infant and Toddler Development II or III. RESULTS: Seventy seven of one hundred one (76%) eligible infants participated in the follow-up study. Neurodevelopmental outcomes were not different in the scGOS/lcFOS/pAOS and placebo group. Infections during the neonatal period, lower percentages of bifidobacteria at day 7 (F = 3.8, P = 0.05) and day 14 (F = 5.0, P = 0.02) and higher levels of Interleukine (IL)-1beta (F = 4.0, P = 0.04) and IL-8 (F = 8.0, P = 0.01) at day 7 are associated with lower mental developmental index. Lower psychomotor outcomes are associated with IL-2 (F = 4.0, P = 0.05), IL-4 (F = 6.0, P = 0.02) at birth, and interferon gamma at day 7 (F = 4.4, P = 0.04). CONCLUSIONS: scGOS/lcFOS/pAOS showed no significant improvement of neurodevelopmental outcomes at 24 months in preterm infants. Infections, lower bifidobacteria counts, and higher serum cytokine levels during the neonatal period were associated with lower neurodevelopmental outcomes at 24 months of age indicating the relevance of microbiome and immune responses in neurodevelopmental processes. PMID- 26859092 TI - Intestinal Microbiota in Pediatric Surgical Cases Administered Bifidobacterium Breve: A Randomized Controlled Trial. AB - The efficacy of perioperative probiotic administration has been reported in adults. We examined the effects of orally administered Bifidobacterium breve strain Yakult (BBG-01) on outcomes in pediatric surgical cases by assessing intestinal and blood microbiota. BBG-01 was well tolerated without adverse effects, and postoperative infectious complications were significantly decreased. Fecal analysis showed increased Bifidobacterium and decreased Enterobacteriaceae, Clostridium difficile, and Pseudomonas. Concentrations of fecal acetic acid were significantly increased, maintaining fecal pH at <7.0. The incidence of detecting bacteria in blood was significantly reduced. BBG-01 improved the intestinal environment, and may be implicated in suppressing bacterial translocation. PMID- 26859093 TI - ABCD: Anthropometry, Body Composition, and Crohn Disease. AB - BACKGROUND: Young individuals with Crohn disease (CD) are at risk of poor bone mineral density (BMD) and reduced lean tissue mass (LTM). The importance of LTM for maintaining skeletal health, in both incident and established CD, is evidenced. We used dual-energy x-ray absorptiometry assessment to identify areal BMD and LTM in individuals with CD. METHODS: In 57 patients with CD (15F; 12.99 14.16 years) anthropometric, disease activity, bone age assessment, and total body dual-energy x-ray absorptiometry measurements were acquired. A 4-step algorithm was used to assess simultaneous bone and body composition data: areal BMD and height z scores, and LTM for height and bone mineral content (BMC) for LTM z scores were calculated. Low z score cut-off values were defined as <=1 standard deviations below the population means. RESULTS: The CD cohort showed: low areal BMD z scores (P = 0.00); and low LTM for height (P = 0.00) according to defined cut-off values. BMC appeared to be adapting for the lower amount of LTM. Correcting for bone age eliminated the low areal BMD z scores. As expected, LTM for height and BMC for LTM z scores remained unchanged. CONCLUSIONS: We present a useful clinical algorithm to show significant LTM for height deficits, regardless of chronological or bone age, in this CD cohort. BMC seemed to adapt to the reduced LTM, indicating clinically "normal" areal BMD for age when considered for height. The ongoing deficits in LTM may, however, create chronic long-term consequences for bone health. Improving LTM should be a focus of clinical treatment in individuals with CD. PMID- 26859094 TI - Additional Protein Fortification Is Necessary in Extremely Low-Birth-Weight Infants Fed Human Milk. AB - In the present study, approximately one in three (49/152, 32.2%) extremely low birth-weight infants were demonstrated to require additional protein intake to supplement the standard fortification to achieve satisfactory weight gain. This additional protein fortification also resulted in a rapid increase in length-for age (P < 0.001) and head circumference-for-age (P = 0.02) z scores. PMID- 26859095 TI - Magnetic magnetite (Fe3O4) nanoparticle synthesis and applications for lead (Pb2+) and chromium (Cr6+) removal from water. AB - Magnetic magnetite (Fe3O4) nanoparticles synthesized by chemical co-precipitation were characterized using XRD, TEM, SEM-EDX, FT-IR, ED-XRF, PPMS, point of zero charge (pHpzc) and surface area measurements. As-prepared Fe3O4 nanoparticles were successful for aqueous Cr(6+) and Pb(2+) removal. Batch adsorption experiments systematically investigated the influence of pH, temperature, contact time and adsorbate/adsorbent concentration on Cr(6+) and Pb(2+) adsorption. Maximum Cr(6+) and Pb(2+) removal occurred at pH 2.0 and 5.0, respectively. Sorption data fit pseudo-second order kinetics, indicating a chemical adsorption. The Freundlich, Langmuir, Redlich-Peterson, Toth, Radke and Sips adsorption isotherm models were applied to describe equilibrium data. The Sips and Langmuir models best described Cr(6+) and Pb(2+) adsorption on magnetite nanoparticles, respectively. The maximum Langmuir adsorption capacities were 34.87 (Cr(6+)) and 53.11 (Pb(2+))mg/g at 45 degrees C, respectively. Fe3O4 nanoparticles are promising potential adsorbents and exhibited remarkable reusability for metal ions removal in water and wastewater treatment. PMID- 26859096 TI - The FIKK kinase of Toxoplasma gondii is not essential for the parasite's lytic cycle. AB - FIKK kinases are a novel family of kinases unique to the Apicomplexa. While most apicomplexans encode a single FIKK kinase, Plasmodium falciparum expresses 21 and piroplasms do not encode a FIKK kinase. FIKK kinases share a conserved C-terminal catalytic domain, but the N-terminal region is highly variable and contains no known functional domains. To date, FIKK kinases have been primarily studied in P. falciparum and Plasmodium berghei. Those that have been studied are exported from the parasite and associate with diverse locations in the infected erythrocyte cytosol or membrane. Deletion of individual P. falciparum FIKK kinases indicates that they may play a role in modification of the infected erythrocyte. The current study characterises the single FIKK gene in Toxoplasma gondii to evaluate the importance of the FIKK kinase in an apicomplexan that has a single FIKK kinase. The TgFIKK gene encoded a protein of approximately 280kDa. Endogenous tagging of the FIKK protein with Yellow Fluorescent Protein showed that the FIKK protein exclusively localised to the posterior end of tachyzoites. A Yellow Fluorescent Protein-tagged FIKK and a Ty-tagged FIKK both co-localised with T. gondii membrane occupation and recognition nexus protein to the basal complex and were localised apical to inner membrane complex protein-5 and Centrin2. Deletion of TgFIKK, surprisingly, had no detectable effect on the parasite's lytic cycle in vitro in human fibroblast cells or in acute virulence in vivo. Thus, our results clearly show that while the FIKK kinase is expressed in tachyzoites, it is not essential for the lytic cycle of T. gondii. PMID- 26859098 TI - Iminoboronate-Based Peptide Cyclization That Responds to pH, Oxidation, and Small Molecule Modulators. AB - As a rich source of therapeutic agents, peptide natural products usually adopt a cyclic or multicyclic scaffold that minimizes structural flexibility to favor target binding. Inspired by nature, chemists have been interested in developing synthetic cyclic and multicyclic peptides that serve as biological probes and potential therapeutics. Herein we describe a novel strategy for peptide cyclization in which intramolecular iminoboronate formation allows spontaneous cyclization under physiologic conditions to yield monocyclic and bicyclic peptides. Importantly the iminoboronate-based cyclization can be rapidly reversed in response to multiple stimuli, including pH, oxidation, and small molecules. This highly versatile strategy for peptide cyclization should find applications in many areas of chemical biology. PMID- 26859097 TI - Safe and sound? A systematic literature review of seizure detection methods for personal use. AB - PURPOSE: The study aims to review systematically the quality of evidence supporting seizure detection devices. The unpredictable nature of seizures is distressing and disabling for sufferers and carers. If a seizure can be reliably detected then the patient or carer could be alerted. It could help prevent injury and death. METHODS: A literature search was completed. Forty three of 120 studies found using relevant search terms were suitable for systematic review which was done applying pre-agreed criteria using PRISMA guidelines. The papers identified and reviewed were those that could have potential for everyday use of patients in a domestic setting. Studies involving long term use of scalp electrodes to record EEG were excluded on the grounds of unacceptable restriction of daily activities. RESULTS: Most of the devices focused on changes in movement and/or physiological signs and were dependent on an algorithm to determine cut off points. No device was able to detect all seizures and there was an issue with both false positives and missed seizures. Many of the studies involved relatively small numbers of cases or report on only a few seizures. Reports of seizure alert dogs are also considered. CONCLUSION: Seizure detection devices are at a relatively early stage of development and as yet there are no large scale studies or studies that compare the effectiveness of one device against others. The issue of false positive detection rates is important as they are disruptive for both the patient and the carer. Nevertheless, the development of seizure detection devices offers great potential in the management of epilepsy. PMID- 26859099 TI - Retroperitoneal Laparoendoscopic Single-Incision Radical Nephrectomy Without Special Platforms: A Single-Center Initial Experience. AB - OBJECTIVES: To describe the initial experience of retroperitoneal laparoendoscopic single-incision radical nephrectomy (LESI-RN) without special platforms and use of conventional laparoscopic instruments and assess the safety and feasibility of LESI-RN. SUBJECTS AND METHODS: Twenty patients who underwent LESI-RN were enrolled in this study. A 5-cm arc skin incision was performed at the midpoint between the costal arch and iliac crest on the midaxillary line. Trocars of 10, 5, and 11 mm were placed at the middle, left end, and right end of the arc incision, respectively. Demographic parameters and perioperative data were retrospectively analyzed and compared with the patients who underwent conventional retroperitoneal laparoscopic radical nephrectomy (LRN). RESULTS: The LESI-RN patients had a significantly lower visual analogue scale (4.4 +/- 1.9 versus 5.6 +/- 1.4; P = .031) and analgesic requirement (18.5 +/- 11.2 versus 28.6 +/- 16.1; P = .026) compared with the conventional LRN group. The operation time in the LESI-RN group was longer than that in the conventional LRN group (P = .001). The two procedures were essentially similar in terms of the time to liquid intake and hospital stay after operation (P > .05). CONCLUSIONS: LESI-RN is a safe and feasible surgical strategy, which combines the common principles of using straight instruments and working triangulation in conventional LRN with advantages of cosmesis and minimal invasiveness in laparoendoscopic single-site surgery. The surgical and oncological efficacy of LESI-RN is similar to that of conventional LRN but with significantly improved control of postoperative pain and cosmetic results. PMID- 26859100 TI - Evidence of DMSO-Induced Protein Aggregation in Cells. AB - We report on a study of protein aggregation induced on different cell samples by dimethyl sulfoxide (DMSO) addition. DMSO is the most commonly used cryoprotectant because it is supposed to readily diffuse across lipid bilayers, thus reducing water activity within cells; despite its large use, the mechanism of penetration and even the main interaction features with cell components are far from being understood. In the present work, infrared absorption spectroscopy is successfully applied to real time detection of chemical and structural changes occurring in cells during dehydration from water and water/DMSO suspensions. As a most interesting result, DMSO is observed to favor protein aggregation both in cellular model systems, as cultured lymphocytes and fibroblasts, and in human samples for clinic use, as hematopoietic stem cells from cord blood. This effect is evidenced at low water content, analogously to what is observed for protein solutions. Such tendency is not specific of the type of protein and suggests one possible origin of DMSO toxicity. PMID- 26859102 TI - Contemporary Reproductive Outcomes for Patients With Polycystic Ovary Syndrome: A Retrospective Observational Study. AB - CONTEXT: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility and may be associated with adverse pregnancy and neonatal outcomes. However, it is difficult to establish how much of this risk is due to PCOS and how much to obesity. OBJECTIVE: This study aimed to determine the effect of PCOS upon fertility, pregnancy, and neonatal outcomes. DESIGN AND SETTING: Data were extracted from the Clinical Practice Research Datalink (CPRD), a longitudinal anonymized primary care research database in the United Kingdom. Patients with a diagnosis of PCOS were matched to controls (1:2) by age (+/-1 y), body mass index (+/- 3 U), and CPRD practice. Standardized fertility ratios before and after diagnosis (index date) were calculated. Rates of miscarriage, pre-eclampsia, gestational diabetes, premature delivery, delivery method, and neonatal outcomes were compared. RESULTS: Nine thousand sixty-eight women with PCOS matched study criteria. Prior to index date the standardized fertility ratio for patients with PCOS was 0.80 (95% confidence interval, 0.77-0.83); following index date it was 1.16 (1.12-1.20). The adjusted odds ratios (95% CI) for miscarriage (1.70; 1.56 1.84), pre-eclampsia (1.32; 1.16-1.49), gestational diabetes (1.41; 1.2-1.66), and premature delivery (1.25; 1.1-1.43) were all increased compared with controls. Of PCOS births, 27.7% were by Caesarean section compared with 23.7% of controls (1.13; 1.05-1.21). Infants born to mothers with PCOS had an increased risk of neonatal jaundice (1.20; 1.03-1.39) and respiratory complications (1.20; 1.06-1.37). CONCLUSIONS: PCOS is associated with subfertility but fertility rates are restored to those of the background population following diagnosis. Pregnancy complications and adverse neonatal outcomes are more prevalent for women with PCOS independently of obesity. PMID- 26859101 TI - Fulvestrant decreases anastrozole drug concentrations when taken concurrently by patients with metastatic breast cancer treated on SWOG study S0226. AB - AIMS: In the SWOG S0226 trial the combination of anastrozole plus fulvestrant (n = 349) was superior to anastrozole alone (n = 345) in hormone receptor (HR) positive metastatic breast cancer. Here we report a pharmacokinetic subset analysis investigating a possible drug interaction between anastrozole and fulvestrant. METHODS: Post-menopausal patients with HR-positive metastatic breast cancer were randomized to anastrozole with or without concurrent fulvestrant. Blood samples were collected at 2, 4, 6 and 8 months, just prior to receiving the next dose of anastrozole and fulvestrant. Drug concentrations were measured via LC/MS-MS. Anastrozole concentration was compared in patients on anastrozole alone vs. patients on concomitant fulvestrant. Comparisons were made at each time point using parametric tests and over time using a linear mixed effects model. RESULTS: A total of 483 anastrozole concentration measurements were included, 224 samples from 64 patients on the anastrozole alone arm and 259 from 73 patients on the combination arm. The mean anastrozole concentration in the combination arm was significantly lower than that in the anastrozole alone arm at each sample collection time (all P < 0.01) and in the mixed effects model (an estimated difference of 9.85 ng ml(-1) (95% CI 5.69, 14.00 ng ml(-1) ), P < 0.001). CONCLUSION: A significant pharmacokinetic drug interaction was detected, in which the addition of fulvestrant to anastrozole treatment decreased the trough anastrozole concentration. Further research is needed to verify whether this interaction affects treatment efficacy and to determine the pharmacological mechanism by which this interaction occurs. PMID- 26859103 TI - Long-Term Insulin Independence in Type 1 Diabetes Mellitus Using a Simplified Autologous Stem Cell Transplant. AB - CONTEXT: Efforts to find a cure for type 1 diabetes have focused on the removal of the autoimmune pathophysiologic substrate, with the use of immunosuppressive regimens including autologous hematopoietic stem cell transplantation (AHSCT). OBJECTIVE: The main objective of determining long-term insulin independence as well as changes in glycated hemoglobin (HbA1c). Secondary outcomes were procedure morbidity and the need for hospital management. DESIGN: We enrolled patients with type 1 diabetes between 2012 and 2014. Median follow-up was 34 months (range, 25 56 mo). SETTING: Ambulatory care. INTERVENTIONS: We decided to carry out an AHSCT protocol using a less toxic and affordable simplified method based on fludarabine in an outpatient setting. PATIENTS: Patients were of both sexes, age 8-25 years, with positive levels of anti-GAD antibodies, a C-peptide level >1.0 ng/mL, and <3 months since diagnosis. MAIN OUTCOME MEASURE(S): Insulin independence. RESULTS: Sixteen patients were included. Overall response was 81% with seven patients achieving insulin independence (44%); six were partial responders (37%) whereas three were nonresponders (19%). The HbA1c level showed a mean decrease of -2.3% at 6 months in the Insulin Independence group. Median age was 12 years old (range, 8-17 years old). A mean of 11.5 * 10(6) CD34+ cells (SD +/- 8.2) was obtained. Related mortality at 100 days was 0% as well as during follow-up. Outpatient setting was 100%. CONCLUSIONS: Simplified AHSCT in an outpatient setting is a feasible, safe and potentially therapeutic intervention for early onset type 1 diabetes. PMID- 26859104 TI - Cord Blood Ferritin and Fibroblast Growth Factor-23 Levels in Neonates. AB - CONTEXT: Elevated levels of the phosphate-regulating hormone, fibroblast growth factor-23 (FGF-23) are associated with skeletal and cardiovascular disease. Levels of FGF-23 are elevated in neonates, but the mechanisms are poorly understood. Iron deficiency is a recently described stimulus for FGF-23 production. OBJECTIVE: To test the hypothesis that lower fetal iron status, as measured by lower cord blood ferritin, is independently associated with elevated FGF-23 levels in neonates. DESIGN AND PARTICIPANTS: This is a cross-sectional study of 64 full-term, healthy neonates. SETTING: This study took place in a university-based, tertiary care center. MAIN OUTCOME MEASURES: Plasma levels of second generation C-terminal FGF-23 (cFGF-23) and intact FGF-23 (iFGF-23). RESULTS: Levels of cFGF-23 ranged from 108 to 7508 reference units (RU)/ml (median, 824 RU/ml), and iFGF-23 from undetectable (<8.5) to 135.4 pg/ml (median, <8.5 pg/mL). Ferritin ranged from 58 to 719 ng/ml (mean, 203 ng/ml). Lower cord blood ferritin levels were associated with higher cFGF-23 (r = -0.320; P = .014), but not iFGF-23 levels (r = -0.222; P = .082). In multivariate analyses adjusted for glycemic indices, maternal race, and parity, lower ferritin levels remained independently associated with higher cFGF-23 levels (B = -0.261, P = .01). In the full models, higher cord blood glucose and C-peptide levels were also independently associated with higher cFGF-23 levels. CONCLUSIONS: cFGF-23, but not iFGF-23 levels, are elevated in cord blood of healthy term neonates and independently associated with lower serum ferritin and higher glycemic indices. PMID- 26859105 TI - Glucose Complexity Estimates Insulin Resistance in Either Nondiabetic Individuals or in Type 1 Diabetes. AB - Glucose entropy was inversely correlated with insulin resistance in a series of non-diabetic individuals with low glucose variability. In long-standing type 1 diabetes, the inverse correlation between glucose entropy and insulin resistance is preserved, as lower glucose entropy is associated with higher BMI. PMID- 26859107 TI - [Annual Scientific Meeting of German Psychosomatic Medicine and Psychotherapy]. PMID- 26859106 TI - Differential Effects of Teriparatide and Denosumab on Intact PTH and Bone Formation Indices: AVA Osteoporosis Study. AB - We compared effects of teriparatide and denosumab on PTH, bone turnover markers, and bone histomorphometry in osteoporotic postmenopausal women. The findings were inconsistent with an early indirect anabolic effect of denosumab. PMID- 26859108 TI - [Effort-Reward Imbalance in Household and Family Work--Analysing the Psychometric Properties among Fathers of Underage Children]. AB - Recently, the concept of effort-reward imbalance (ERI) developed by Siegrist had been applied to unpaid household and family work (ERI-HF). Evidence suggests that the imbalance between effort spent and reward received in family and domestic labor is associated with poor mental and physical health. However, so far, the adopted questionnaire ERI-HF was exclusively used among women in childcare responsibility. This paper reports on the application of the model to men in childcare responsibility using data from a clinical sample of fathers in rehabilitation clinics (N=415). Analogous to the original version, ERI-HF is divided into 2 components: (i) dysbalance of effort and reward, and (ii) overcommitment. For both components, confirmatory factor analyses revealed good to satisfactory properties. Overall, 13.4% of men in childcare responsibility showed a dysbalance between high effort and low reward of household and family work. High levels of effort were more frequently reported than high levels of low reward. With percentages ranging between 24.3 and 59.6%, a significant proportion of fathers reported difficulties to withdraw from household and family work obligations. Analyses of construct validity revealed significant associations between ERI and socio-demographic factors (number of children, employment status, single fatherhood, work-family-conflict) as well as subjective health. Taken together, our findings suggest that the instrument is applicable to men in childcare responsibility. PMID- 26859109 TI - [Guidelines for Trainings in Inter-/Transcultural Competence for Psychotherapists]. AB - BACKGROUND: The ongoing globalization leads to the fact that intercultural aspects are becoming more important in recent years. Unfortunately, the psychosocial sector in general as well as psychotherapists in particular are not sufficiently trained for those issues. In the German speaking countries so far there were no guidelines for the conceptualization of intercultural trainings for psychotherapists. In the present study guidelines for trainings of inter /transcultural competence of medical and psychological psychotherapists have been developed. METHODS: An extensive data base was collected including a systematic international literature research, qualitative expert interviews, a quantitative survey among therapists and 8 focus groups with clients as well as therapists from different cultural backgrounds. The guidelines for trainings were then extracted in a 2-step consensus procedure. RESULTS: The guidelines define learning objectives which should be achieved in a training. They also describe the structural as well as substantive requirements which should be met in such a training. In addition to knowledge on cultural issues that should be acquired in a training the guidelines put high emphasis on the self reflection of training participants on their own cultural embededness as well as on the aquisition of culturally sensitive skills. DISCUSSION: Regarding demographic trends in Germany trainings for intercultural competence should become an obligatory element in the training of psychotherapists. The guidelines represent a high-quality base for the conceptualization as well as the evaluation of such trainings. CONCLUSION: The guidelines developed here represent an instrument for the improvement of the training of therapists in Germany in the field of transcultural psychology. In the long term they could contribute to the intercultural opening of the German mental health system and improve the quality of psychotherapeutical treatment of migrants in Germany. PMID- 26859110 TI - [Psychotraumatological Defence Mechanisms in the Print Media Coverage of 'September 11']. AB - INTRODUCTION: Media have a significant influence on the perception of mental disorders in society. Especially in the case of traumatizations, the indirect confrontation with a traumatic event will lead to the application of psychotraumatological defence mechanisms aiming at retaining an illusory sense of security. Experts assume that journalists are also making use of psychotraumatological defence when reporting on disasters in print media. This, in turn, will influence the reception of traumatic events in the public in general and in the construction of victim and perpetrator in particular. APPROACH: Is there evidence of the employment of psychotraumatological defence mechanisms on the part of the journalists to be found in the German and American print media coverage of 'September 11'? METHODS: All the articles (N=260) published about the 'September 11' (11 Sep-11 Oct 2001) in 3 German and American newspapers were evaluated by content analyses. RESULTS: In 195 of the N=260 articles analysed, the occurrence of psychotraumatological defence mechanisms could be confirmed (in 74% of the German and 76% of the American articles). The comparison between tabloid and quality print media showed that tabloid journalism tends to make more use of defence strategies (evident in 84% of the German and 86% of the American tabloid press articles). CONCLUSIONS: On the basis of these findings a guideline for the compilation of an "optimal article" has been developed with the purpose of preventing the use of psychotraumatological defence. PMID- 26859111 TI - [Helpful Factors of Ambulant Art Therapy in the Group and Changes of Experiences in Psychosomatic Patients]. AB - The aim of this study was to analyze the experiences of patients suffering from mostly chronic psychosomatic disorders in an ambulant art therapy in the group. Especially, the focus was on the experienced changes, helpful factors and specifics of the therapy as well as on the experienced benefit. For this, 30 patients were interviewed in a semi-standardized way. Additionally, the symptom based strain was psychometrically recorded in a part of the patients (21) at the beginning of the therapy and after at least 6 months of participation. The evaluation of those interviews with the qualitative analysis of the therapy subjects surrendered an improvement of the health state in most of the participants. Especially group factors, art as a mean of communication, becoming aware of feelings but also diversion and fun were proved to be beneficial. The art therapy also serves for structuring the week as well as a contact point and a resource in the interpersonal communication of everyday life. Nearly all of the patients referred to some important turning point pictures. Mostly, the benefit was valued as being high. But, in contrast, the psychometric measure did not show any significant change. The results emphasize the stabilizing function of art therapy in the examined patients, whereat the classification of the psychometric result is complicated by the absence of a control group. PMID- 26859112 TI - [Stress in Medical Students: A Cross-Sectional Study on the Relevance of Attachment Style and Structural Integration]. AB - INTRODUCTION: From year one of studying medicine an increase of psychological stress is found. The relationship between the occurrence of this stress and attachment patterns or structural personality functions remains unclear. The present study aimed at investigating whether a relationship between the enduring personality variables, attachment style and level of structural integration of the personality, and acute stress experience at the beginning of medical students' studies exists. MATERIAL & METHODS: In this study, all students in the first semester of medicine were invited to participate in a study to identify stress factors via questionnaire (MBI-SS, PSQ, PHQ-9, GAD-7) in the WS 2013/2014. Simultaneously, the predominant attachment style (RQ-2) and structural abilities (OPD-SFK) were evaluated. RESULTS: The study included 293 students (return: 91.3%). Securely attached students experienced significantly less stress than insecurely attached students (p=0.019). Students with a high level of structural integration showed significantly less stress burden (p<0.001) and lower exhaustion- (p<0.001) and cynicism values (p<0.001), while showing a higher experience of self-efficacy (p<0.001). The influence of attachment behavior on stress experience is mediated by the level of the structural integration of the personality. DISCUSSION: Significant correlations exist between attachment style and the level of structural integration of the personality, and burnout risk as well as stress burden. The level of structural integration of the personality mediates the relationship between the attachment-related "model of self" and stress experience, i. e. a positive "model of self" can have a stress-protective effect when good structural abilities are present. Practical implication: An insecure attachment style and a low level of structural integration may be associated with higher stress experience when transitioning to study. The results suggest that the enduring personality variable attachment style, mediated by the level of structural integration of the personality, leads to higher stress and burnout experience. Affected students could be supported by early preventive measures enabling the sustainable preparation for this transitional period. Longitudinal prospective studies are needed to explore if the assumption is applicable that pre-existing vulnerabilities in school are exacerbated at this transitional stage. PMID- 26859113 TI - [Ambulatory Assessment in Clinical and Psychological Research]. PMID- 26859114 TI - Icariside II inhibits the EMT of NSCLC cells in inflammatory microenvironment via down-regulation of Akt/NF-kappaB signaling pathway. AB - Inflammatory microenvironment created by immune cells is favorable for tumor metastasis. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in inflammatory microenvironment. In this study, we sought to investigate the effects of Icariside II, a flavonol glycoside isolated from Epimedium koreanum Nakai, on A549 and H1299 cells migration in inflammatory microenvironment. At non-cytotoxic concentrations, Icariside II could inhibit invasion and EMT of A549 and H1299 cells induced by LPS-stimulated-THP-1 medium or by pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha). Exposure to Icariside II resulted in the increment of E cadherin, accompanied with decrement of N-cadherin, vimentin, Slug, and Snail in A549 and H1299 cells stimulated by TNF1alpha. Furthermore, Icariside II suppressed TNF-alpha-triggered nuclear translocation of NF-kappaB and phosphorylation of IkappaBalpha, and repressed the DNA-binding activity of NF kappaB. Further data demonstrated that Akt/GSK-3beta, other than MAPK signaling pathway was taking a part in the inhibitory potential of Icariside II on NF kappaB activation. Importantly, Icariside II also impeded lung metastasis of A549 cells and EMT in nude mice. In conclusion, Icariside II might prohibit invasion through inactivating Akt/NF-kappaB pathway. (c) 2016 Wiley Periodicals, Inc. PMID- 26859115 TI - In vivo characterization of regenerative peripheral nerve interface function. AB - OBJECTIVE: Regenerative peripheral nerve interfaces (RPNIs) are neurotized free autologous muscle grafts equipped with electrodes to record myoelectric signals for prosthesis control. Viability of rat RPNI constructs have been demonstrated using evoked responses. In vivo RPNI characterization is the next critical step for assessment as a control modality for prosthetic devices. APPROACH: Two RPNIs were created in each of two rats by grafting portions of free muscle to the ends of divided peripheral nerves (peroneal in the left and tibial in the right hind limb) and placing bipolar electrodes on the graft surface. After four months, we examined in vivo electromyographic signal activity and compared these signals to muscular electromyographic signals recorded from autologous muscles in two rats serving as controls. An additional group of two rats in which the autologous muscles were denervated served to quantify cross-talk in the electrode recordings. Recordings were made while rats walked on a treadmill and a motion capture system tracked the hind limbs. Amplitude and periodicity of signals relative to gait were quantified, correlation between electromyographic and motion recording were assessed, and a decoder was trained to predict joint motion. MAIN RESULTS: Raw RPNI signals were active during walking, with amplitudes of 1 mVPP, and quiet during standing, with amplitudes less than 0.1 mVPP. RPNI signals were periodic and entrained with gait. A decoder predicted bilateral ankle motion with greater than 80% reliability. Control group signal activity agreed with literature. Denervated group signals remained quiescent throughout all evaluations. SIGNIFICANCE: In vivo myoelectric RPNI activity encodes neural activation patterns associated with gait. Signal contamination from muscles adjacent to the RPNI is minimal, as demonstrated by the low amplitude signals obtained from the Denervated group. The periodicity and entrainment to gait of RPNI recordings suggests the transduced signals were generated via central nervous system control. PMID- 26859116 TI - The preparation of novel adsorbent materials with efficient adsorption performance for both chromium and methylene blue. AB - The hydroxy-functionalized ionic liquids (ILs) modified with magnetic chitosan/grapheneoxide (MG-ILs-OH) were synthesized. The surface morphology of MG ILs-OH was characterized by transmission electron microscopy, X-ray diffraction, thermo gravimetric analysis and Fourier transform infrared spectroscopy techniques. It was found that the adsorption kinetics is well fitted by a pseudo second-order model and the adsorption isotherms agree well with the Langmuir model, and the MG-ILs-OH could be repeatedly used by simple treatment. The results showed that the addition of ILs-OH can largely increase the adsorption sites (hydroxy and amino groups) and adsorption properties. The MG-ILs-OH were used as adsorbent for the removal of methylene blue (MB) and Cr(VI) from simulated wastewater with a fast solid-liquid separation in the presence of external magnetic field. The maximum obtained adsorption capacities of MB and Cr(VI) were 243.31 and 107.99 mg/g, respectively. The application of MG-ILs-OH could effectively solve the problem that the adsorbent only adsorb similar adsorbate. PMID- 26859117 TI - Large amino acid transporter 1 mediated glutamate modified docetaxel-loaded liposomes for glioma targeting. AB - The therapeutic outcome of glioma treatment is rigorously limited by blood-brain barrier (BBB) and infiltrating growth of glioma. To tackle the dilemma, more and more attentions were focused on developing nutrient transporters-mediated dual targeted drug delivery system, in one side for BBB penetration, another for intracranial glioma targeting. Herein, Large amino acid transporter 1 (LAT1), overexpressed both on BBB and glioma cells, was selected as a target. Docetaxel loaded glutamate-d-alpha-tocopherol polyethylene glycol 1000 succinate copolymer (Glu-TPGS) functionalized LAT1-targeting liposomes (DTX-TGL) were applied to enhance the BBB penetration and glioma therapy. The in vivo results of the fluorescent image indicated that TGL possessed an effective BBB penetration than that of unmodified ones in mice. The LAT1 targeting effcicacy and cell cytotoxicity of TGL were investigated in C6 glioma cells. Compared with unmodified liposomes, a significant higher cellular uptake and cell cytotoxicity was found in TGL treated group. Our results indicated that LAT1-targeting docetaxel-loaded liposome paves up a new direction using LAT1 transporter as a good target in designing brain glioma-targeting nanosystems. PMID- 26859118 TI - Stomach specific polymeric low density microballoons as a vector for extended delivery of rabeprazole and amoxicillin for treatment of peptic ulcer. AB - The study was intended to develop a new intra-gastric floating in situ microballoons system for controlled delivery of rabeprazole sodium and amoxicillin trihydrate for the treatment of peptic ulcer disease. Eudragit S-100 and hydroxypropyl methyl cellulose based low density microballoons systems were fabricated by employing varying concentrations of Eudragit S-100 and hydroxypropyl methyl cellulose, to which varying concentrations of drug was added, and formulated by stirring at various speed and time to optimize the process and formulation variable. The formulation variables like concentration and ratio of polymers significantly affected the in vitro drug release from the prepared floating device. The validation of the gastro-retentive potential of the prepared microballoons was carried out in rabbits by orally administration of microballoons formulation containing radio opaque material. The developed formulations showed improved buoyancy and lower ulcer index as compared to that seen with plain drugs. Ulcer protective efficacies were confirmed in ulcer bearing mouse model. In conclusion, greater compatibility, higher gastro retention and higher anti-ulcer activity of the presently fabricated formulations to improve potential of formulation for redefining ulcer treatment are presented here. These learning exposed a targeted and sustained drug delivery potential of prepared microballoons in gastric region for ulcer therapeutic intervention as corroborated by in vitro and in vivo findings and, thus, deserves further attention for improved ulcer treatment. PMID- 26859119 TI - A new strategy based on electrospray technique to prepare dual-responsive poly(ether urethane) nanogels. AB - In this work, we proposed a new strategy based on electrospray technique to prepare nanogels. Compared with other methods of preparing nanogels, electrospray technique is more simple and efficient. A biodegradable and multi-responsive poly(ether urethane) (PEU) was synthesized via a facile one-pot method and used as the electrospray material. By using electrospray technique, pH- and redox responsive poly(ether urethane) nanogels were prepared. The morphologies of the electrospray nanoparticles before and after swelling were demonstrated to be spherical and uniform, as characterized by scanning electron microscope (SEM) and transmission electron microscopy (TEM). Dynamic light scattering (DLS) results showed that the mean hydrodynamic diameter of nanogels was about 500 nm. The pH- and redox-sensitive behaviors of nanogels were studied with DLS and TEM. In acidic media the nanogels dissociated, while in the presence of GSH the nanogels degraded. The nanogels suspension was stored at 4 degrees C and was stable without aggregation for at least 30 days. Doxorubicin (DOX) can be further loaded into the poly(ether urethane) nanogels. The electrospray nanogels can change the release rate of loaded drug in response to pH and GSH stimuli. PMID- 26859120 TI - Agglutination of human erythrocytes by the interaction of Zn(2+)ion with histidine-651 on the extracellular domain of band 3. AB - Clustering of band 3, chloride/bicarbonate exchanger, has been reported in Zn(2+) treated human erythrocytes. However, the agglutination of human erythrocytes is also induced by the interaction of Zn(2+)ion with histidine on band 3. Identification of histidine that interacts with Zn(2+)ion remains to be determined. The Zn(2+)-induced agglutination of human erythrocytes was unaffected by chymotrypsin cleavage of the small loop region containing His-547 in the extracellular domain of band 3. On the other hand, papain digestion of the large loop region containing His-651 in band 3 inhibited such Zn(2+)-induced agglutination. Moreover, Zn(2+)-induced erythrocyte agglutination was inhibited by the peptide (ARGWVIHPLG) containing His-651, but not by the peptide such as ARGWVIRPLG, which His-651 was substituted by arginine. Among 10 kinds of animal erythrocytes tested, interestingly, no agglutination by Zn(2+)ions was observed in cow cells only that the forth amino acid in the upstream from His-669 on the large loop of cow band 3 is aspartate (Asp-665) instead of glycine. As expected, the agglutination of human erythrocytes by Zn(2+) ions was inhibited in the presence of aspartate. These data indicate that the interaction of Zn(2+) ion with His-651 residue of band 3 plays an important role in the Zn(2+)-induced agglutination of human erythrocytes. PMID- 26859121 TI - The importance of extracellular speciation and corrosion of copper nanoparticles on lung cell membrane integrity. AB - Copper nanoparticles (Cu NPs) are increasingly used in various biologically relevant applications and products, e.g., due to their antimicrobial and catalytic properties. This inevitably demands for an improved understanding on their interactions and potential toxic effects on humans. The aim of this study was to investigate the corrosion of copper nanoparticles in various biological media and to elucidate the speciation of released copper in solution. Furthermore, reactive oxygen species (ROS) generation and lung cell (A549 type II) membrane damage induced by Cu NPs in the various media were studied. The used biological media of different complexity are of relevance for nanotoxicological studies: Dulbecco's modified eagle medium (DMEM), DMEM(+) (includes fetal bovine serum), phosphate buffered saline (PBS), and PBS+histidine. The results show that both copper release and corrosion are enhanced in DMEM(+), DMEM, and PBS+histidine compared with PBS alone. Speciation results show that essentially no free copper ions are present in the released fraction of Cu NPs in neither DMEM(+), DMEM nor histidine, while labile Cu complexes form in PBS. The Cu NPs were substantially more membrane reactive in PBS compared to the other media and the NPs caused larger effects compared to the same mass of Cu ions. Similarly, the Cu NPs caused much more ROS generation compared to the released fraction only. Taken together, the results suggest that membrane damage and ROS formation are stronger induced by Cu NPs and by free or labile Cu ions/complexes compared with Cu bound to biomolecules. PMID- 26859122 TI - One-step thermolysis synthesis of two-dimensional ultrafine Fe3O4 particles/carbon nanonetworks for high-performance lithium-ion batteries. AB - To tackle the issue of inferior cycle stability and rate capability for Fe3O4 anode materials in lithium ion batteries, ultrafine Fe3O4 nanocrystals uniformly encapsulated in two-dimensional (2D) carbon nanonetworks have been fabricated through thermolysis of a simple, low-cost iron(iii) acetylacetonate without any extra processes. Moreover, compared to the reported Fe3O4/carbon composites, the particle size of Fe3O4 is controllable and held down to ~3 nm. Benefitting from the synergistic effects of the excellent electroconductive carbon nanonetworks and uniform distribution of ultrafine Fe3O4 particles, the prepared 2D Fe3O4/carbon nanonetwork anode exhibits high reversible capacity, excellent rate capability and superior cyclability. A high capacity of 1534 mA h g(-1) is achieved at a 1 C rate and is maintained without decay up to 500 cycles (1 C = 1 A g(-1)). Even at the high current density of 5 C and 10 C, the 2D Fe3O4/carbon nanonetworks maintain a reversible capacity of 845 and 647 mA h g(-1) after 500 discharge/charge cycles, respectively. In comparison with other reported Fe3O4 based anodes, the 2D Fe3O4/carbon nanonetwork electrode is one of the most attractive of those in energy storage applications. PMID- 26859123 TI - Solitary Pouch Ulcer: A New Clinical Entity? AB - Solitary rectal ulcer syndrome is a well-known clinical entity, likely secondary to a defecatory dysfunction. In patients who have undergone restorative proctocolectomy with ileoanal reservoir, it is conceivable that a similar pathophysiology may lead to "solitary pouch ulcer," but such a syndrome has not been reported to date. This article reports 2 such cases and clinical success with lasting symptomatic relief through local therapy and behavior modification rather than anti-inflammatory. PMID- 26859125 TI - Interleukin-23R gene polymorphism in pediatric Egyptian patients with primary immune thrombocytopenia. AB - Primary immune thrombocytopenia is an acquired autoimmune disorder caused by the production of antiplatelet antibodies. These autoantibodies opsonize platelets for splenic clearance, resulting in low levels of circulating platelets. The current case-control study aimed at detecting the frequency of interleukin-23 receptor rs1884444 single nucleotide polymorphism in Egyptian children with primary immune thrombocytopenia and its possible role as a genetic marker for disease risk. Interleukin-23 receptor rs1884444 single nucleotide polymorphism was studied in 50 patients with primary immune thrombocytopenia and 100 healthy age and sex-matched controls by polymerase chain reaction amplification of the target gene followed by allele-specific restriction enzyme digestion. Regarding the distribution of the genotypes of the interleukin-23 receptor rs1884444 polymorphism, no statistically significant difference was found between cases and control groups. The variant genotypes (GT/TT) frequency was 10% in primary immune thrombocytopenia cases versus 7% in the control groups [P value = 0.755, odds ratio (OR): 0.326, 95% confidence interval (CI): 0.099-1.076]. Similarly, no difference was found between acute and chronic cases. The variant genotypes GT/TT frequency was 10.7% in acute versus 9.1% in chronic primary immune thrombocytopenia (P value = 0.849). The variant genotypes GT/TT were not found to be a risk factor for acute primary (P value = 0.807, OR: 0.641, 95% CI: 0.16 2.563) or chronic primary immune thrombocytopenia (P value = 0.914, OR: 0.762, 95% CI: 0.153-3.797). Our study suggests the possibility that interleukin-23 receptor gene polymorphism may not contribute to the susceptibility of development of primary immune thrombocytopenia in Egyptian children. PMID- 26859126 TI - Twenty-one-gene recurrence score assay in BRCA-associated versus sporadic breast cancers: Differences based on germline mutation status. AB - BACKGROUND: Biological differences between BRCA-associated breast cancer and sporadic breast cancer may warrant different adjuvant chemotherapy (ACRx) recommendations despite similar phenotypic features. A 21-gene expression profile (Oncotype DX) generates a prognostic recurrence score (RS) that predicts the ACRx benefit in patients with hormone receptor-positive breast cancer. No reports describe assay results for BRCA-associated breast cancer. METHODS: A review of Memorial Sloan Kettering Cancer Center databases identified 4908 patients with hormone receptor-positive, node-negative breast cancer who underwent Oncotype DX testing between July 2006 and March 2014. BRCA1/BRCA2 carriers (cases) were identified and matched (1:2) by age at diagnosis and tumor size to noncarrier controls. Two-sample nonparametric tests were used to compare the baseline characteristics, RSs, and risk stratification between BRCA1 and BRCA2 patients. Conditional logistic regression was used to assess these differences by mutational status. RESULTS: Fifty mutation-associated cases (19 BRCA1 cases and 31 BRCA2 cases) and 100 controls who were well matched for age (P = .9) and tumor size (P = .6) were included. BRCA1 and BRCA2 carriers had similar median RSs (P = .6) and risk category stratification (P = .3). The median RS was higher for cases versus controls (24 vs 16; P < .0001). Risk stratification also differed by mutational status (P = .0002). Cases had more high-risk disease (28% vs 7%) and intermediate-risk disease (56% vs 36%) and less low-risk disease (16% vs 57%). Cases were more likely than controls to receive ACRx (74% vs 46%; P = .002). CONCLUSIONS: Germline BRCA-associated hormone receptor-positive breast cancer may be associated with intrinsically less favorable biology. Few affected carriers have RS indicating a clear absence of benefit from ACRx. The increased use of ACRx and benefit from ACRx in BRCA carriers may mitigate otherwise inferior outcomes. PMID- 26859127 TI - Prognostic significance of EZH2 expression in patients with oesophageal cancer: a meta-analysis. AB - Enhancer of zeste 2 (EZH2), a key component of polycomb repressive complex 2 (PRC2), was of great importance in human cancer pathogenesis. Various studies examined the relationship between EZH2 overexpression with the clinical outcome in patients with digestive cancers, but yielded conflicting results. Electronic databases updated to January 2015 were searched to find relevant studies. A meta analysis was conducted with eligible studies which quantitatively evaluated the relationship between EZH2 overexpression and survival of patients with digestive cancers. Survival data were aggregated and quantitatively analysed. We performed a meta-analysis of 10 studies (n = 1461 patients) that evaluated the correlation between EZH2 overexpression and survival in patients with digestive cancers. Combined hazard ratios suggested that EZH2 overexpression was associated with poor prognosis of overall survival (HR = 1.54, 95% CI: 1.27-1.81) in patients with oesophageal cancer. In the stratified analysis, no significant risks were found among gastric cancer (HR = 0.66, 95% CI: 0.16-1.15) and colorectal cancer (HR = 0.91, 0.63-1.19), indicating that EZH2 was not an indicator of poor prognosis in gastric cancer or colorectal cancer. Enhancer of zeste 2 overexpression indicates a poor prognosis for patients with oesophageal cancer, but not among gastric cancer or colorectal cancer. PMID- 26859128 TI - Climate data, localisation of the sting, grade of anaphylaxis and therapy of hymenoptera stings. AB - International epidemiological studies indicate that around 1-7% of the population respond with an allergic reaction to a hymenoptera sting, which is frequently associated with admission to an emergency department. This retrospective study included patients admitted between 2009 and 2013 to an emergency department after a hymenoptera sting. In all, 86 (60.1%) men and 57 (39.9%) women were included in the study. The mean age was 43 years, with a range from 19 to 84 years. The most common localisations of a sting were the head (n = 33; 22.5%), the hands (n = 32; 21.9%) and the arms (n = 26; 17.8%). In women, we recorded significantly more stings in distal extremities (p = 0.033) and in men stings in the rump and head were most frequent. Local swellings were observed in 67.1% (n = 96) of patients and 34.3% (n = 49) patients exhibited an anaphylactic reaction. Of these, 21.7% (n = 31) suffered from a grade I, 6.3% (n = 9) grade II, 4.2% (n = 6) grade III and 2.1% (n = 3) grade IV anaphylactic reactions. 46% (66) of the patients were given antihistamines, 45% (64) intravenous glucocorticoids and only 12.5% (16) epinephrine. Most stings were recorded on days without rainfall (p = 0.013), with more hours of sunshine (p = 0.001), low relative humidity (p = 0.006), with mean air pressure above 954.3 hPa and on days with mean temperature above 24.2 degrees C (p = 0.001). In conclusion, the most hymenoptera stings induced local swelling only; severe reactions were rare. The most dangerous stings are enoral and result from inattentive drinking. Epinephrine was rarely used in anaphylactic reactions. PMID- 26859129 TI - Spontaneous endogenous pulsatile release of kisspeptin is temporally coupled with luteinizing hormone in healthy women. AB - OBJECTIVE: To evaluate the presence of a spontaneous pulsatile release of kisspeptin and whether it is temporally coupled to LH pulses. DESIGN: Experimental study. SETTING: Academic medical center. PATIENT(S): Thirty young healthy eumenorrheic women aged 20-37 years were included in the study group. All subjects were white women admitted to the Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland. INTERVENTION(S): Kisspeptin, FSH, LH, E2, PRL, and insulin were evaluated in all subjects at baseline. MAIN OUTCOME MEASURE(S): All women underwent a pulsatility study measuring LH and kisspeptin plasma concentrations to assess the spontaneous episodic secretion of both hormones, sampling every 10 minutes for 2 hours from 9:00 to 11:00 a.m. for a total of 12 blood samples. Detection and specific concordance (SC) algorithms were used to detect pulses and their concordance. RESULT(S): A significant endogenous secretory pattern was demonstrated for both LH and kisspeptin over the 2-hour duration of the study (2.4 +/- 0.1 peaks/2 h). The computation of the SC index showed for the first time that kisspeptin and LH are cosecreted and temporally coupled at time "0," and their peaks occur at the same point in time. CONCLUSION(S): The present study provides evidence supporting the hypothesis that kisspeptin is highly relevant in the regulation and modulation of reproductive functions in humans. PMID- 26859130 TI - Live birth of twins derived from zona-free oocytes. AB - OBJECTIVE: To report a live birth of twins from autologous zona-free oocytes. DESIGN: Case report. SETTING: Reproductive endocrinology and infertility private practice and ambulatory in vitro fertilization (IVF) center. PATIENT(S): A 34 year-old woman, gravida 0, with 100% zona-free oocytes. INTERVENTION(S): IVF with intracytoplasmic sperm injection (ICSI), blastocyst culture, and fresh embryo transfer. MAIN OUTCOME MEASURE(S): Fertilization, blastocyst development, and live birth. RESULT(S): A 34-year-old woman, gravida 0, conceived through IVF using autologous zona-free oocytes. The 11 retrieved oocytes were zona-free, from which eight were inseminated with ICSI; two embryos were transferred at morula and blastocyst stage, resulting in a twin pregnancy delivered at an estimated the gestational age of 37 weeks and 1 day. CONCLUSION(S): Patients with the rare condition of 100% zona-free oocytes maintain the potential for pregnancy after careful micromanipulation of the oocytes. Caution is recommended on the number of embryos selected for transfer to reduce the risk of multiple gestation. PMID- 26859131 TI - Primary vitreoretinal lymphoma: an update on pathogenesis, diagnosis and treatment. AB - PURPOSE OF REVIEW: Primary vitreoretinal lymphoma (PVRL) is a subset of primary central nervous system lymphoma in which disease primarily affects the uvea, retina, vitreous and optic nerve. This review discusses recent efforts to clarify the disease's pathogenesis, its diagnosis and its optimal treatment. RECENT FINDINGS: PVRL typically masquerades as a chronic intermediate uveitis in older individuals. Unambiguous diagnosis requires cytologic demonstration of malignant cells in a vitreous or chorioretinal specimen. However, cytokine analysis demonstrating increased interleukin 10 (IL 10) levels or increased IL-10:IL-6 ratio in the aqueous or vitreous, flow cytometry demonstrating a monoclonal cell population, molecular analysis demonstrating gene rearrangements or translocations or combinations of several techniques can be used effectively to aid in diagnosis. Treatment is aimed at eradication of disease within the eyes and prevention of central nervous system (CNS) lymphoma. Whether this should be done with local therapy alone (globe irradiation or intravitreal chemotherapy such as methotrexate or rituximab), or with systemic chemotherapy remains a source of debate. Even with high-dose systemic chemotherapy, CNS disease is prone to recurrence and has a poor prognosis. SUMMARY: New techniques and innovative treatment strategies may streamline time to definitive diagnosis and may lead to prolonged survival with better vision in patients with PVRL. PMID- 26859132 TI - Cell therapy for retinal disease. AB - PURPOSE OF REVIEW: The following review will provide an update on stem cell therapy with a focus on completed and ongoing human trials. RECENT FINDINGS: Significant progress has brought stem cell therapy from proof-of-concept animal models to human clinical trials. Although in its infancy, valuable safety and efficacy data are starting to emerge from trials looking at cell therapies for age-related macular degeneration, Stargardt's macular dystrophy, retinitis pigmentosa, and ischemic retinopathies. SUMMARY: Although clinical trials continue to enroll and evaluate stem cell therapy in patients with retinal diseases, preliminary results using both cellular replacement and trophic models have provided initial support for this exciting therapy. Results of these pivotal trials will form a key foundation for moving forward toward the ultimate goal of preventing blinding disease. PMID- 26859133 TI - Historical DNA documents long-distance natal homing in marine fish. AB - The occurrence of natal homing in marine fish remains a fundamental question in fish ecology as its unequivocal demonstration requires tracking of individuals from fertilization to reproduction. Here, we provide evidence of long-distance natal homing (>1000 km) over more than 60 years in Atlantic cod (Gadus morhua), through genetic analysis of archived samples from marked and recaptured individuals. Using a high differentiation single-nucleotide polymorphism assay, we demonstrate that the vast majority of cod tagged in West Greenland and recaptured on Icelandic spawning grounds belonged to the Iceland offshore population, strongly supporting a hypothesis of homing. The high degree of natal fidelity observed provides the evolutionary settings for development of locally adapted populations in marine fish and emphasize the need to consider portfolio effects in marine fisheries management strategies. PMID- 26859134 TI - Different Gene Expression Signatures in Children and Adults with Celiac Disease. AB - Celiac disease (CD) is developed after gluten ingestion in genetically susceptible individuals. It can appear at any time in life, but some differences are commonly observed between individuals with onset early in life or in adulthood. We aimed to investigate the molecular basis underlying those differences. We collected 19 duodenal biopsies of children and adults with CD and compared the expression of 38 selected genes between each other and with the observed in 13 non-CD controls matched by age. A Bayesian methodology was used to analyze the differences of gene expression between groups. We found seven genes with a similarly altered expression in children and adults with CD when compared to controls (C2orf74, CCR6, FASLG, JAK2, IL23A, TAGAP and UBE2L3). Differences were observed in 13 genes: six genes being altered only in adults (IL1RL1, CD28, STAT3, TMEM187, VAMP3 and ZFP36L1) and two only in children (TNFSF18 and ICOSLG); and four genes showing a significantly higher alteration in adults (CCR4, IL6, IL18RAP and PLEK) and one in children (C1orf106). This is the first extensive study comparing gene expression in children and adults with CD. Differences in the expression level of several genes were found between groups, being notorious the higher alteration observed in adults. Further research is needed to evaluate the possible genetic influence underlying these changes and the specific functional consequences of the reported differences. PMID- 26859135 TI - Activity of Synthetic Antimicrobial Peptide GH12 against Oral Streptococci. AB - Controlling the growth of cariogenic microorganisms such as oral streptococci is an adjunct therapy for caries-active individuals to prevent and treat caries. Here we investigated the antimicrobial activity of the synthetic amphipathic alpha- helical antimicrobial peptide GH12 (GLLWHLLHHLLH-NH2) against oral streptococci in vitro. Circular dichroism studies showed that GH12 takes on an alpha-helical conformation in the presence of membrane-mimicking solvents, and reversed-phase high-performance liquid chromatography studies showed that GH12 remains stable in saliva. The peptide showed bactericidal activity against oral streptococci, with minimum inhibitory concentrations ranging from 6.7 to 32.0 MUg/ml. GH12 concentrations 4-fold higher than the minimum bactericidal concentration completely killed oral streptococci within 20 min. Treating oral streptococci with GH12 caused noticeable changes in bacterial viability and morphology based on confocal laser scanning microscopy and scanning electron microscopy. Effects of GH12 on biofilm formation and on viability of mature biofilm were quantified by crystal violet staining and the 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyltetrazolium bromide assay. GH12 effectively inhibited biofilm formation and metabolic activity in biofilms of oral streptococci, especially S. mutans, S. sobrinus and S. salivarius. These results suggest that GH12 shows rapid and strong antimicrobial activity against oral streptococci in vitro, opening the door to preclinical and clinical studies to explore its potential for caries prevention and treatment. PMID- 26859136 TI - A Systematic Review on the Characteristics, Treatments and Outcomes of the Patients with Primary Spinal Glioblastomas or Gliosarcomas Reported in Literature until March 2015. AB - Our aim was to determine the characteristics, treatments and outcomes of patients with primary spinal glioblastomas (GB) or gliosarcomas (GS) reported in literature until March 2015. PubMed and Web of Science were searched for peer reviewed articles pertaining to cases of glioblastomas / gliosarcomas with primary spinal origin, using predefined search terms. Furthermore we performed hand searches tracking the references from the selected papers. Eighty-two articles published between 1938 and March 2015 were eligible. They reported on 157 patients. Median age at diagnosis was 22 years. The proportion of patients who received adjuvant chemo- or radiotherapy clearly increased from the time before 1980 until present. Median overall survival from diagnosis was 8.0 +/- 0.9 months. On univariate analysis age influenced overall survival, whereas tumor location, gender and the extent of initial resection did not. Outcomes did not differ between children (< 18 years) and adults. However, the patients who were treated after 1980 achieved longer survival times than the patients treated before. On multivariable analysis only age (< 60 years) and the time period of treatment (>= 1980) were confirmed as positive independent prognostic factors. In conclusion, primary spinal GB / GS mainly affect younger patients and are associated with a dismal prognosis. However, most likely due to the increasing use of adjuvant treatment, modest therapeutic progress has been achieved over recent decades. The characteristics and treatments of primary spinal glioblastomas should be entered into a central registry in order to gain more information about the ideal treatment approach in the future. PMID- 26859137 TI - What Population Reveals about Individual Cell Identity: Single-Cell Parameter Estimation of Models of Gene Expression in Yeast. AB - Significant cell-to-cell heterogeneity is ubiquitously observed in isogenic cell populations. Consequently, parameters of models of intracellular processes, usually fitted to population-averaged data, should rather be fitted to individual cells to obtain a population of models of similar but non-identical individuals. Here, we propose a quantitative modeling framework that attributes specific parameter values to single cells for a standard model of gene expression. We combine high quality single-cell measurements of the response of yeast cells to repeated hyperosmotic shocks and state-of-the-art statistical inference approaches for mixed-effects models to infer multidimensional parameter distributions describing the population, and then derive specific parameters for individual cells. The analysis of single-cell parameters shows that single-cell identity (e.g. gene expression dynamics, cell size, growth rate, mother-daughter relationships) is, at least partially, captured by the parameter values of gene expression models (e.g. rates of transcription, translation and degradation). Our approach shows how to use the rich information contained into longitudinal single cell data to infer parameters that can faithfully represent single-cell identity. PMID- 26859138 TI - In Silico Identification of Protein Disulfide Isomerase Gene Families in the De Novo Assembled Transcriptomes of Four Different Species of the Genus Conus. AB - Small peptides isolated from the venom of the marine snails belonging to the genus Conus have been largely studied because of their therapeutic value. These peptides can be classified in two groups. The largest one is composed by peptides rich in disulfide bonds, and referred to as conotoxins. Despite the importance of conotoxins given their pharmacology value, little is known about the protein disulfide isomerase (PDI) enzymes that are required to catalyze their correct folding. To discover the PDIs that may participate in the folding and structural maturation of conotoxins, the transcriptomes of the venom duct of four different species of Conus from the peninsula of Baja California (Mexico) were assembled. Complementary DNA (cDNA) libraries were constructed for each species and sequenced using a Genome Analyzer Illumina platform. The raw RNA-seq data was converted into transcript sequences using Trinity, a de novo assembler that allows the grouping of reads into contigs without a reference genome. An N50 value of 605 was established as a reference for future assemblies of Conus transcriptomes using this software. Transdecoder was used to extract likely coding sequences from Trinity transcripts, and PDI-specific sequence motif "APWCGHCK" was used to capture potential PDIs. An in silico analysis was performed to characterize the group of PDI protein sequences encoded by the duct transcriptome of each species. The computational approach entailed a structural homology characterization, based on the presence of functional Thioredoxin-like domains. Four different PDI families were characterized, which are constituted by a total of 41 different gene sequences. The sequences had an average of 65% identity with other PDIs. Using MODELLER 9.14, the homology-based three dimensional structure prediction of a subset of the sequences reported, showed the expected thioredoxin fold which was confirmed by a "simulated annealing" method. PMID- 26859139 TI - Anti-Inflammatory and Antioxidant Actions of N-Arachidonoyl Serotonin in RAW264.7 Cells. AB - The purpose of this study is to evaluate the effect of N-arachidonoyl serotonin (NA-5HT) on inflammatory response or oxidative stress in RAW264.7 cells exposed to lipopolysaccharide (LPS). When RAW264.7 cells were pre-incubated with NA-5HT before LPS treatment, NA-5HT was found to suppress LPS-induced formation of nitric oxide (NO), tumor necrosis factor-alpha or interleukins as well as expression of inducible NO synthase and cyclooxygenase-2 at non-cytotoxic concentrations. Consistent with this, NA-5HT efficiently reversed LPS-induced phosphorylative activation of nuclear factor-kappaB pathway probably through the suppression of mitogen-activated protein kinases (MAPKs) pathway or phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. Separately, NA-5HT enhanced the antioxidant capacity accompanied by nuclear translocation of nuclear factor-E2-related factor-2 (Nrf2) in RAW264.7 cells. Additionally, NA-5HT induced nuclear translocation of Nrf2 was suppressed significantly by the inhibition of c-Jun N-terminal kinase1/2 or PI3K/Akt pathways, although NA-5HT phosphorylated signal molecules in MAPKs and PI3K/Akt pathways. Taken together, NA-5HT is proposed to exert anti-inflammatory and antioxidant actions in RAW264.7 cells. PMID- 26859140 TI - Correction: Abdominal Muscle Activity during Mechanical Ventilation Increases Lung Injury in Severe Acute Respiratory Distress Syndrome. PMID- 26859142 TI - The Effects on the Femoral Cortex of a 24 Month Treatment Compared to an 18 Month Treatment with Teriparatide: A Multi-Trial Retrospective Analysis. AB - BACKGROUND: Teriparatide (TPTD) is an anabolic agent indicated for the treatment of severely osteoporotic patients who are at high risk of fragility fractures. The originally approved duration of TPTD treatment in several regions, including Europe, was 18 months. However, studies of areal bone mineral density (aBMD) showed additional benefit when treatment is continued beyond 18 months, and the drug is currently licenced for 24 months. Improvements in cortical structure at the proximal femur have already been shown in patients given TPTD for 24 months using quantitative computed tomography (QCT). Here, we investigate whether cortical and endocortical trabecular changes differ between an 18- and 24-month treatment. METHODS: Since an 18- versus 24-month TPTD study using QCT has not been conducted, we studied combined QCT data from four previous clinical trials. Combined femoral QCT data from three 18-month TPTD studies ('18-month group') were compared with data from a fourth 24-month trial ('24-month group'). Cortical parameters were measured over the entire proximal femur which allowed for a comparison of the mean changes as well as a visual comparison of the colour maps of changes after 18 and 24 months TPTD. RESULTS: For both the combined 18-month group and the 24-month group, overall cortical thickness and endocortical trabecular density increased, while overall cortical bone mineral density decreased. While the changes in the 24-month group were of greater magnitude compared to the 18-month group, the differences were only significant for the endocortical trabecular density (ECTD), corrected for age, weight, femoral neck T score, total hip T-score and the baseline mean ECTD. CONCLUSION: Although the combination of data from different clinical trials is not optimal, these data support the concept that the duration of TPTD in the 18-24 month phase is of clinical relevance when considering improvement in hip structure. PMID- 26859141 TI - Integrated microRNA and mRNA Signature Associated with the Transition from the Locally Confined to the Metastasized Clear Cell Renal Cell Carcinoma Exemplified by miR-146-5p. AB - BACKGROUND: MicroRNAs (miRNAs) regulate gene expression by interfering translation or stability of target transcripts. This interplay between miRNA and their mRNA has been proposed as an important process in cancer development and progression. We have investigated molecular networks impacted by predicted mRNA targets of differentially expressed miRNAs in patients with clear cell renal cell carcinoma (ccRCC) diagnosed with or without metastasis. MATERIAL AND METHODS: miRNA and mRNA microarray expression profiles derived from primary ccRCC from patients with (16 samples) or without diagnosed metastasis (22 samples) were used to identify anti-correlated miRNA-mRNA interaction in ccRCC. For this purpose, Ingenuity pathway analysis microRNA Target Filter, which enables prioritization of experimentally validated and predicted mRNA targets was used. By applying an expression pairing tool, the analysis was focused on targets exhibiting altered expression in our analysis, finding miRNAs and their target genes with opposite or same expression. The resulting identified interactions were revalidated by RT qPCR in another cohort of ccRCC patients. A selection of the predicted miRNA-mRNA interactions was tested by functional analyses using miRNA knockdown and overexpression experiments in renal cancer cell lines. RESULTS: Among the significantly differentially expressed miRNAs, we have identified three miRNAs (miR-146a-5p, miR-128a-3p, and miR-17-5p) that were upregulated in primary tumors from patients without metastasis and downregulated in primary tumors from patients with metastasis. We have further identified mRNA targets, which expression were inversely correlated to these 3 miRNAs, and have been previously experimentally demonstrated in cancer setting in humans. Specifically, we showed that CXCL8/IL8, UHRF1, MCM10, and CDKN3 were downregulated and targeted by miR 146a-5p. The interaction between miR-146a-5p and their targets CXCL8 and UHRF1 was validated in cell culture experiments. CONCLUSIONS: We identified novel target genes of dysregulated miRNAs, which are involved in the transition from primary RCC without metastases into tumors generating distant metastasis. PMID- 26859143 TI - Uncovering a Nuisance Influence of a Phenological Trait of Plants Using a Nonlinear Structural Equation: Application to Days to Heading and Culm Length in Asian Cultivated Rice (Oryza Sativa L.). AB - Phenological traits of plants, such as flowering time, are linked to growth phase transition. Thus, phenological traits often influence other traits through the modification of the duration of growth period. This influence is a nuisance in plant breeding because it hampers genetic evaluation of the influenced traits. Genetic effects on the influenced traits have two components, one that directly affects the traits and one that indirectly affects the traits via the phenological trait. These cannot be distinguished by phenotypic evaluation and ordinary linear regression models. Consequently, if a phenological trait is modified by introgression or editing of the responsible genes, the phenotypes of the influenced traits can change unexpectedly. To uncover the influence of the phenological trait and evaluate the direct genetic effects on the influenced traits, we developed a nonlinear structural equation (NSE) incorporating a nonlinear influence of the phenological trait. We applied the NSE to real data for cultivated rice (Oryza sativa L.): days to heading (DH) as a phenological trait and culm length (CL) as the influenced trait. This showed that CL of the cultivars that showed extremely early heading was shortened by the strong influence of DH. In a simulation study, it was shown that the NSE was able to infer the nonlinear influence and direct genetic effects with reasonable accuracy. However, the NSE failed to infer the linear influence in this study. When no influence was simulated, an ordinary bi-trait linear model (OLM) tended to infer the genetic effects more accurately. In such cases, however, by comparing the NSE and OLM using an information criterion, we could assess whether the nonlinear assumption of the NSE was appropriate for the data analyzed. This study demonstrates the usefulness of the NSE in revealing the phenotypic influence of phenological traits. PMID- 26859144 TI - Voltage-Induced Ca2+ Release in Postganglionic Sympathetic Neurons in Adult Mice. AB - Recent studies have provided evidence that depolarization in the absence of extracellular Ca2+ can trigger Ca2+ release from internal stores in a variety of neuron subtypes. Here we examine whether postganglionic sympathetic neurons are able to mobilize Ca2+ from intracellular stores in response to depolarization, independent of Ca2+ influx. We measured changes in cytosolic DeltaF/F0 in individual fluo-4 -loaded sympathetic ganglion neurons in response to maintained K+ depolarization in the presence (2 mM) and absence of extracellular Ca2+ ([Ca2+]e). Progressive elevations in extracellular [K+]e caused increasing membrane depolarizations that were of similar magnitude in 0 and 2 mM [Ca2+]e. Peak amplitude of DeltaF/F0 transients in 2 mM [Ca2+]e increased in a linear fashion as the membrane become more depolarized. Peak elevations of DeltaF/F0 in 0 mM [Ca2+]e were ~5-10% of those evoked at the same membrane potential in 2 mM [Ca2+]e and exhibited an inverse U-shaped dependence on voltage. Both the rise and decay of DeltaF/F0 transients in 0 mM [Ca2+]e were slower than those of DeltaF/F0 transients evoked in 2 mM [Ca2+]e. Rises in DeltaF/F0 evoked by high [K+]e in the absence of extracellular Ca2+ were blocked by thapsigargin, an inhibitor of endoplasmic reticulum Ca2+ ATPase, or the inositol 1,4,5 triphosphate (IP3) receptor antagonists 2-aminoethoxydiphenyl borate and xestospongin C, but not by extracellular Cd2+, the dihydropyridine antagonist nifedipine, or by ryanodine at concentrations that caused depletion of ryanodine sensitive Ca2+ stores. These results support the notion that postganglionic sympathetic neurons possess the ability to release Ca2+ from IP3-sensitive internal stores in response to membrane depolarization, independent of Ca2+ influx. PMID- 26859145 TI - Establishment of a Refined Oral Glucose Tolerance Test in Pigs, and Assessment of Insulin, Glucagon and Glucagon-Like Peptide-1 Responses. AB - Diabetes mellitus is increasing worldwide and reliable animal models are important for progression of the research field. The pig is a commonly used large animal model in diabetes research and the present study aimed to refine a model for oral glucose tolerance test (OGTT) in young growing pigs, as well as describing intravenous glucose tolerance test (IVGTT) in the same age group. The refined porcine OGTT will reflect that used in children and adolescents. Eighteen pigs were obtained one week after weaning and trained for two weeks to bottle feed glucose solution, mimicking the human OGTT. The pigs subsequently underwent OGTT (1.75 g/kg BW) and IVGTT (0.5 g/kg BW). Blood samples were collected from indwelling vein catheters for measurements of glucose and the diabetes related hormones insulin, glucagon and active glucagon-like peptide-1. The study confirmed that pigs can be trained to bottle-feed glucose dissolved in water and thereby undergo an OGTT more similar to the human standard OGTT than previously described methods in pigs. With the refined method for OGTT, oral intake only consists of glucose and water, which is an advantage over previously described methods in pigs where glucose is given together with feed which will affect glucose absorption. Patterns of hormonal secretion in response to oral and intravenous glucose were similar to those in humans; however, the pigs were more glucose tolerant with lower insulin levels than humans. In translational medicine, this refined OGTT and IVGTT methods provide important tools in diabetes research when pigs are used as models for children and adolescents in diabetes research. PMID- 26859146 TI - Trophic and Non-Trophic Interactions in a Biodiversity Experiment Assessed by Next-Generation Sequencing. AB - Plant diversity affects species richness and abundance of taxa at higher trophic levels. However, plant diversity effects on omnivores (feeding on multiple trophic levels) and their trophic and non-trophic interactions are not yet studied because appropriate methods were lacking. A promising approach is the DNA based analysis of gut contents using next generation sequencing (NGS) technologies. Here, we integrate NGS-based analysis into the framework of a biodiversity experiment where plant taxonomic and functional diversity were manipulated to directly assess environmental interactions involving the omnivorous ground beetle Pterostichus melanarius. Beetle regurgitates were used for NGS-based analysis with universal 18S rDNA primers for eukaryotes. We detected a wide range of taxa with the NGS approach in regurgitates, including organisms representing trophic, phoretic, parasitic, and neutral interactions with P. melanarius. Our findings suggest that the frequency of (i) trophic interactions increased with plant diversity and vegetation cover; (ii) intraguild predation increased with vegetation cover, and (iii) neutral interactions with organisms such as fungi and protists increased with vegetation cover. Experimentally manipulated plant diversity likely affects multitrophic interactions involving omnivorous consumers. Our study therefore shows that trophic and non-trophic interactions can be assessed via NGS to address fundamental questions in biodiversity research. PMID- 26859147 TI - Parallel Evolution of Polydactyly Traits in Chinese and European Chickens. AB - Polydactyly is one of the most common hereditary congenital limb malformations in chickens and other vertebrates. The zone of polarizing activity regulatory sequence (ZRS) is critical for the development of polydactyly. The causative mutation of polydactyly in the Silkie chicken has been mapped to the ZRS; however, the causative mutations of other chicken breeds are yet to be established. To understand whether the same mutation decides the polydactyly phenotype in other chicken breeds, we detected the single-nucleotide polymorphism in 26 different chicken breeds, specifically, 24 Chinese indigenous breeds and 2 European breeds. The mutation was found to have fully penetrated chickens with polydactyly in China, indicating that it is causative for polydactyly in Chinese indigenous chickens. In comparison, the mutation showed no association with polydactyly in Houdan chickens, which originate from France, Europe. Based on the different morphology of polydactyly in Chinese and European breeds, we assumed that the trait might be attributable to different genetic foundations. Therefore, we subsequently performed genome-wide association analysis (GWAS) to locate the region associated with polydactyly. As a result, a ~0.39 Mb genomic region on GGA2p was identified. The region contains six candidate genes, with the causative mutation found in Chinese indigenous breeds also being located in this region. Our results demonstrate that polydactyly in chickens from China and Europe is caused by two independent mutation events that are closely located in the chicken genome. PMID- 26859148 TI - Ocean Acidification Affects Hemocyte Physiology in the Tanner Crab (Chionoecetes bairdi). AB - We used flow cytometry to determine if there would be a difference in hematology, selected immune functions, and hemocyte pH (pHi), under two different, future ocean acidification scenarios (pH = 7.50, 7.80) compared to current conditions (pH = 8.09) for Chionoecetes bairdi, Tanner crab. Hemocytes were analyzed after adult Tanner crabs were held for two years under continuous exposure to acidified ocean water. Total counts of hemocytes did not vary among control and experimental treatments; however, there were significantly greater number of dead, circulating hemocytes in crabs held at the lowest pH treatment. Phagocytosis of fluorescent microbeads by hemocytes was greatest at the lowest pH treatment. These results suggest that hemocytes were dying, likely by apoptosis, at a rate faster than upregulated phagocytosis was able to remove moribund cells from circulation at the lowest pH. Crab hemolymph pH (pHe) averaged 8.09 and did not vary among pH treatments. There was no significant difference in internal pH (pHi) within hyalinocytes among pH treatments and the mean pHi (7.26) was lower than the mean pHe. In contrast, there were significant differences among treatments in pHi of the semi-granular+granular cells. Control crabs had the highest mean semi-granular+granular pHi compared to the lowest pH treatment. As physiological hemocyte functions changed from ambient conditions, interactions with the number of eggs in the second clutch, percentage of viable eggs, and calcium concentration in the adult crab shell was observed. This suggested that the energetic costs of responding to ocean acidification and maintaining defense mechanisms in Tanner crab may divert energy from other physiological processes, such as reproduction. PMID- 26859149 TI - High-Dose Fluoride Impairs the Properties of Human Embryonic Stem Cells via JNK Signaling. AB - Fluoride is a ubiquitous natural substance that is often used in dental products to prevent dental caries. The biphasic actions of fluoride imply that excessive systemic exposure to fluoride can cause harmful effects on embryonic development in both animal models and humans. However, insufficient information is available on the effects of fluoride on human embryonic stem cells (hESCs), which is a novel in vitro humanized model for analyzing the embryotoxicities of chemical compounds. Therefore, we investigated the effects of sodium fluoride (NaF) on the proliferation, differentiation and viability of H9 hESCs. For the first time, we showed that 1 mM NaF did not significantly affect the proliferation of hESCs but did disturb the gene expression patterns of hESCs during embryoid body (EB) differentiation. Higher doses of NaF (2 mM and above) markedly decreased the viability and proliferation of hESCs. The mode and underlying mechanism of high dose NaF-induced cell death were further investigated by assessing the sub cellular morphology, mitochondrial membrane potential (MMP), caspase activities, cellular reactive oxygen species (ROS) levels and activation of mitogen-activated protein kinases (MAPKs). High-dose NaF caused the death of hESCs via apoptosis in a caspase-mediated but ROS-independent pathway, coupled with an increase in the phospho-c-Jun N-terminal kinase (p-JNK) levels. Pretreatment with a p-JNK specific inhibitor (SP600125) could effectively protect hESCs from NaF-induced cell death in a concentration- and time-dependent manner. These findings suggest that NaF might interfere with early human embryogenesis by disturbing the specification of the three germ layers as well as osteogenic lineage commitment and that high-dose NaF could cause apoptosis through a JNK-dependent pathway in hESCs. PMID- 26859153 TI - Correlation Between Chain Architecture and Hydration Water Structure in Polysaccharides. AB - The physical properties of confined water can differ dramatically from those of bulk water. Hydration water associated with polysaccharides provides a particularly interesting example of confined water, because differences in polysaccharide structure provide different spatially confined environments for water sorption. We have used attenuated total reflection infrared (ATR-IR) spectroscopy to investigate the structure of hydration water in films of three different polysaccharides under controlled relative humidity (RH) conditions. We compare the results obtained for films of highly branched, dendrimer-like phytoglycogen nanoparticles to those obtained for two unbranched polysaccharides, hyaluronic acid (HA), and chitosan. We find similarities between the water structuring in the two linear polysaccharides and significant differences for phytoglycogen. In particular, the results suggest that the high degree of branching in phytoglycogen leads to a much more well-ordered water structure (low density, high connectivity network water), indicating the strong influence of chain architecture on the structuring of water. These measurements provide unique insight into the relationship between the structure and hydration of polysaccharides, which is important for understanding and exploiting these sustainable nanomaterials in a wide range of applications. PMID- 26859150 TI - Mechanical Stretch Inhibits MicroRNA499 via p53 to Regulate Calcineurin-A Expression in Rat Cardiomyocytes. AB - BACKGROUND: MicroRNAs play an important role in cardiac remodeling. MicroRNA 499 (miR499) is highly enriched in cardiomyocytes and targets the gene for Calcineurin A (CnA), which is associated with mitochondrial fission and apoptosis. The mechanism regulating miR499 in stretched cardiomyocytes and in volume overloaded heart is unclear. We sought to investigate the mechanism regulating miR499 and CnA in stretched cardiomyocytes and in volume overload induced heart failure. METHODS & RESULTS: Rat cardiomyocytes grown on a flexible membrane base were stretched via vacuum to 20% of maximum elongation at 60 cycles/min. An in vivo model of volume overload with aorta-caval shunt in adult rats was used to study miR499 expression. Mechanical stretch downregulated miR499 expression, and enhanced the expression of CnA protein and mRNA after 12 hours of stretch. Expression of CnA and calcineurin activity was suppressed with miR499 overexpression; whereas, expression of dephosphorylated dynamin-related protein 1 (Drp1) was suppressed with miR499 overexpression and CnA siRNA. Adding p53 siRNA reversed the downregulation of miR499 when stretched. A gel shift assay and promoter-activity assay demonstrated that stretch increased p53 DNA binding activity but decreased miR499 promoter activity. When the miR499 promoter p53 binding site was mutated, the inhibition of miR499 promoter activity with stretch was reversed. The in vivo aorta-caval shunt also showed downregulated myocardial miR499 and overexpression of miR499 suppressed CnA and cellular apoptosis. CONCLUSION: The miR499-controlled apoptotic pathway involving CnA and Drp1 in stretched cardiomyocytes may be regulated by p53 through the transcriptional regulation of miR499. PMID- 26859151 TI - Differential Roles for DUSP Family Members in Epithelial-to-Mesenchymal Transition and Cancer Stem Cell Regulation in Breast Cancer. AB - Dual-specificity phosphatases (DUSPs) dephosphorylate threonine/serine and tyrosine residues on their substrates. Here we show that DUSP1, DUSP4, and DUSP6 are involved in epithelial-to-mesenchymal transition (EMT) and breast cancer stem cell (CSC) regulation. DUSP1, DUSP4, and DUSP6 are induced during EMT in a PKC pathway signal-mediated EMT model. We show for the first time that the key chromatin-associated kinase PKC-theta directly regulates a subset of DUSP family members. DUSP1, DUSP4, and DUSP6 globally but differentially co-exist with enhancer and permissive active histone post-translational modifications, suggesting that they play distinct roles in gene regulation in EMT/CSCs. We show that nuclear DUSP4 associates with the key acetyltransferase p300 in the context of the chromatin template and dynamically regulates the interplay between two key phosphorylation marks: the 1834 (active) and 89 (inhibitory) residues central to p300's acetyltransferase activity. Furthermore, knockdown with small-interfering RNAs (siRNAs) shows that DUSP4 is required for maintaining H3K27ac, a mark mediated by p300. DUSP1, DUSP4, and DUSP6 knockdown with siRNAs shows that they participate in the formation of CD44hi/CD24lo/EpCAM+ breast CSCs: DUSP1 knockdown reduces CSC formation, while DUSP4 and DUSP6 knockdown enhance CSC formation. Moreover, DUSP6 is overexpressed in patient-derived HER2+ breast carcinomas compared to benign mammary tissue. Taken together, these findings illustrate novel pleiotropic roles for DUSP family members in EMT and CSC regulation in breast cancer. PMID- 26859152 TI - Demographic and Behavioral Predictors of Severe Fetomaternal Hemorrhage: A Case Control Study. AB - BACKGROUND: Fetomaternal hemorrhage (FMH) signifies failure of the placental barrier with whole blood transfer. Fetal anemia following FMH is associated with significant morbidity and mortality. If FMH is identified early, fetal anemia can be treated to minimize adverse outcomes. Risk factors for FMH are not known, limiting efforts to provide targeted screening for FMH. OBJECTIVE: To identify maternal and/or pregnancy characteristics associated with FMH that are recognizable prior to fetal morbidity. METHODS: This is the first published case control study of FMH. Cases were identified from a prospectively maintained database of all hospital births between 1988 and 2010. Each case was matched to 4 controls by date and time of birth, allowing for assessment of a wide range of clinical and demographic data. Logistic regression modeling was used to assess the association between demographic and clinical characteristics and the diagnosis of FMH. RESULTS: A total of 23 mother-baby pairs impacted by FMH and 92 matched controls were evaluated. Compared to controls, case mothers were more likely to have private insurance and to work outside the home and at night during pregnancy. Cases were more likely to be delivered preterm, but preterm labor was not more common among cases. There was no difference in race/ethnicity of cases compared to controls. CONCLUSIONS: Severe FMH is associated with significant morbidity and mortality of the affected neonate. Women with FMH were more likely to work outside the home during pregnancy than women with normal pregnancies. This finding has implications for third-trimester screening of pregnant women who work in strenuous fields. PMID- 26859154 TI - Influence of supraglottic airway device placement on cerebral hemodynamics. AB - BACKGROUND: Supraglottic airway devices (SGDs) are of current use in anesthesia practice and in emergency conditions. It has been suggested that cerebral blood flow (CBF) can decrease after SGD insertion or cuff inflation; however, it is uncertain if this reduction is caused by the SGD or the anesthetic drugs utilized for the anesthetic procedure. During minor surgery we separated CBF measurements by an adequate time interval in order to measure the distinctive changes in cerebral hemodynamics associated with anesthesia induction, SGD insertion and cuff inflation. METHODS: Patients scheduled for minor surgery requiring general anesthesia and SGD placement were included. Middle cerebral artery mean flow velocity (FVm-mca) and the pulsatility index (PI) were measured through use of trans-cranial Doppler (TCD) at baseline, after anesthesia induction, SGD insertion and cuff inflation, once a steady cardio-circulatory state was reached and end tidal CO2 (etCO2) was within normal range. RESULTS: A total of 21 patients were included. Following anesthesia induction, in concomitance to a reduction in mean arterial pressure (MAP), there was a mean decrease in FVm-mca by 16.60 cm/s, p<0.005 and a mean increase in PI by 0.24, p<0.0015. MAP, FVm-mca and PI did not change significantly, neither after SGD placement (p>0.05), nor after SGD cuffing (p>0.05). CONCLUSION: SGD insertion and cuff inflation did not influence cerebral hemodynamics in anesthetized patients undergoing minor surgery. At normal etCO2 range, the CBF reduction with transient increase in PI was associated with anesthesia induction and not SGD insertion itself. PMID- 26859155 TI - Restrictive versus more liberal blood transfusions? The answer is in your heart. PMID- 26859156 TI - Cycle asynchrony: always a concern during pressure ventilation! PMID- 26859157 TI - When Halides Come to Lithium Niobate Nanopowders Purity and Morphology Assistance. AB - The preparation of pure lithium niobate nanopowders was carried out by a matrix mediated synthesis approach. Lithium hydroxide and niobium pentachloride were used as precursors. The influence of the chemical environment was studied by adding lithium halide (LiCl or LiBr). After thermal treatment of the precursor mixture at 550 degrees C for 30 min, the morphology of the products was obtained from transmission electron microscopy and dynamic light scattering, whereas the crystallinity and phase purity were characterized by X-ray diffraction and UV visible and Raman spectroscopies. Our results point out that the chemical environment during lithium niobate formation at 550 degrees C influences the final morphology. Moreover, direct and indirect band-gap energies have been determined from UV-visible spectroscopy. Their values for the direct-band-gap energies range from 3.97 to 4.36 eV with a slight dependence on the Li/Nb ratio, whereas for the indirect-band-gap energies, the value appears to be independent of this ratio and is 3.64 eV. No dependence of the band-gap energies on the average crystallite and nanoparticle sizes is observed. PMID- 26859158 TI - Ionic Conductivity and Air Stability of Al-Doped Li7La3Zr2O12 Sintered in Alumina and Pt Crucibles. AB - Li7La3Zr2O12 (LLZO) is a promising electrolyte material for all-solid-state battery due to its high ionic conductivity and good stability with metallic lithium. In this article, we studied the effect of crucibles on the ionic conductivity and air stability by synthesizing 0.25Al doped LLZO pellets in Pt crucibles and alumina crucibles, respectively. The results show that the composition and microstructure of the pellets play important roles influencing the ionic conductivity, relative density, and air stability. Specifically, the 0.25Al-LLZO pellets sintered in Pt crucibles exhibit a high relative density (~96%) and high ionic conductivity (4.48 * 10(-4) S cm(-1)). The ionic conductivity maintains 3.6 * 10(-4) S cm(-1) after 3-month air exposure. In contrast, the ionic conductivity of the pellets from alumina crucibles is about 1.81 * 10(-4) S cm(-1) and drops to 2.39 * 10(-5) S cm(-1) 3 months later. The large grains and the reduced grain boundaries in the pellets sintered in Pt crucibles are favorable to obtain high ionic conductivity and good air stability. X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy results suggest that the formation of Li2CO3 on the pellet surface is probably another main reason, which is also closely related to the relative density and the amount of grain boundary within the pellets. This work stresses the importance of synthesis parameters, crucibles included, to obtain the LLZO electrolyte with high ionic conductivity and good air stability. PMID- 26859159 TI - Penetrating the Elusive Mechanism of Copper-Mediated Fluoromethylation in the Presence of Oxygen through the Gas-Phase Reactivity of Well-Defined [LCuO](+) Complexes with Fluoromethanes (CH(4-n)Fn, n = 1-3). AB - Traveling wave ion mobility spectrometry (TWIMS) isomer separation was exploited to react the particularly well-defined ionic species [LCuO](+) (L = 1,10 phenanthroline) with the neutral fluoromethane substrates CH(4-n)Fn (n = 1-3) in the gas phase. Experimentally, the monofluoromethane substrate (n = 1) undergoes both hydrogen-atom transfer, forming the copper hydroxide complex [LCuOH](*+) and concomitantly a CH2F(*) radical, and oxygen-atom transfer, yielding the observable ionic product [LCu](+) plus the neutral oxidized substrate [C,H3,O,F]. DFT calculations reveal that the mechanism for both product channels relies on the initial C-H bond activation of the substrate. Compared to nonfluorinated methane, the addition of fluorine to the substrate assists the reactivity through a lowering of the C-H bond energy and reaction preorganization (through noncovalent interaction in the encounter complex). A two-state reactivity scenario is mandatory for the oxidation, which competitively results in the unusual fluoromethanol product, CH2FOH, or the decomposed products, CH2O and HF, with the latter channel being kinetically disfavored. Difluoromethane (n = 2) is predicted to undergo the analogous reactions at room temperature, although the reactions are less favored than those of monofluoromethane. The reaction of trifluoromethane (n = 3, fluoroform) through C-H activation is kinetically hindered under ambient conditions but might be expected to occur in the condensed phase upon heating or with further lowering of reaction barriers through templation with counterions, such as potassium. Overall, formation of CH(3 n)Fn(*) and CH(3-n)FnOH occurs under relatively gentle energetic conditions, which sheds light on their potential as reactive intermediates in fluoromethylation reactions mediated by copper in the presence of oxygen. PMID- 26859160 TI - Infrared Laser Heating Applied to Nanopore Sensing for DNA Duplex Analysis. AB - Temperature studies coupled with resistive-pulse nanopore sensing enable the quantification of a variety of important thermodynamic properties at the single molecule limit. Previous demonstrations of nanopore sensing with temperature control have utilized bulk chamber heating methodologies. This approach makes it difficult to rapidly change temperatures and enable optical access for other analytical techniques (i.e., single-molecule fluorescence). To address these issues, researchers have explored laser-based methodologies through either direct infrared (IR) absorption or plasmonic assisted heating. In this paper, we demonstrate the use of IR-based direct absorption heating with the DNA sensing capabilities of a biological nanopore. The IR heating enables rapid changes of the temperature in and around an alpha-hemolysin pore, and we use this to explore melting properties for short (<=50 bp) double-stranded DNA homopolymers. We also demonstrate that the IR heating enables one to measure the percentage of different-sized DNA molecules in a binary mixture. PMID- 26859161 TI - Catalytic Asymmetric Synthesis of anti-alpha,beta-Diamino Acid Derivatives. AB - A novel approach to chiral anti-alpha,beta-diamino acid derivatives through tandem orthogonal organocatalysis has been developed. Chiral phosphoric acid catalysts control the chemo-, regio-, and stereoselective addition of hydroxylamines to alkylideneoxazolones, while a phosphine catalyst promotes the isomerization of Z- alkylideneoxazolones to the more reactive E- alkylideneoxazolones. PMID- 26859162 TI - VUV Photodissociation Dynamics of Nitrous Oxide: The N((2)DJ=3/2,5/2) and N((2)PJ=1/2,3/2) Product Channels. AB - We report on an experimental study of the vacuum ultraviolet photodissociation dynamics of nitrous oxide as a function of photolysis wavelength. In this study, both the N((2)DJ) + NO(X(2)Pi) and N((2)PJ) + NO(X(2)Pi) product channels were investigated using the time-sliced velocity ion imaging technique. Images of the N((2)DJ=5/2,3/2) and N((2)PJ=3/2,1/2) products were measured at seven and ten, respectively, photolysis wavelengths between 124.44 and 133.20 nm. The vibrational states of the NO products were partially resolved in the acquired raw ion images. The total kinetic energy release and the branching ratios of different vibrational states of NO products were determined. The vibrational state distributions of NO were found to be inverted for the N((2)DJ=5/2,3/2) and N((2)PJ=3/2,1/2) product channels. This phenomenon indicates that the N-O bond is highly vibrational excited during the breaking of the N-N bond. Vibrational state resolved anisotropic parameters beta in both the N((2)DJ) and the N((2)PJ) channels were acquired. The small beta values (around 0.5) in the dissociation process suggest that transition states in a bent configuration play an important role in the formation of N + NO products. PMID- 26859164 TI - [Job Strain Among Physicians in the Specialty of Psychiatry]. AB - OBJECTIVE: This study aims to examine work related distress in the specialty of psychiatry and psychotherapy. METHODS: With an online survey based on validated stress theories distress prevalence and job satisfaction was examined. RESULTS: 39.4 % (95 %-CI: 35.4 - 44.3) of all respondents (n = 508) showed signs of distress. At the same time 58.5 % (95 %-CI: 53.7 - 63.4) claimed to be satisfied with their job. CONCLUSION: High job satisfaction paired with high distress prevalence can be a sign of a high intrinsic motivation among physicians in the specialty of psychiatry. To prevent this situation to become harmful to one's health, successful coping strategies have to be put in place. PMID- 26859163 TI - Therapeutic Effect of Histone Deacetylase Inhibitor, Sodium Butyrate, on Allergic Rhinitis In Vivo. AB - Despite the well-documented therapeutic effects of histone deacetylase inhibitor (HDACi) on various diseases, including arthritis and asthma, the therapeutic effect of HDACi on allergic rhinitis remains unmentioned in the literature. This study investigated the therapeutic effect of sodium butyrate (SoB), a form of HDACi, on mice with allergic rhinitis. The results showed that the expression levels of histone deacetylase 1 (HDAC1), histone deacetylase 3 (HDAC3), and thymic stromal lymphopoietin (TSLP) were significantly upregulated in mice with allergic rhinitis, whereas H3 acetylation at lysine 9 (H3AcK9) was decreased. The intranasal application of SoB inhibited the expression levels of TSLP levels and upregulated the expression of H3AcK9 in a mouse model of allergic rhinitis. Furthermore, SoB treatment significantly decreased the increased levels of ovalbumin-specific IgE and improved clinical symptoms and nasal mucosa epithelial morphology in the mouse model of allergic rhinitis. In addition, we further demonstrated that SoB treatment significantly increased the serum levels of IL-2 and IFN-gamma and decreased the serum levels of IL-4 and IL-10, correcting the Th1/Th2 imbalance in the mouse model of allergic rhinitis. Taken together, our study suggests that SoB has the potential to treat allergic rhinitis. PMID- 26859165 TI - [Attachment Style, Motives for Use and Internet Addiction]. AB - Background: Attachment theory can contribute to the understanding of the pathogenesis of Internet addiction. Method: An online survey was carried out to assess socio-demographic characteristics, online activity, attachment style, symptoms of Internet addiction and online relationship motives. Results: Participants with secure and insecure attachment style differed in their tendency to abusive Internet use and their online relationship motives. Discussion: These results provide insights into the pathogenesis of Internet addiction. Therapeutic implications are discussed. PMID- 26859166 TI - ["Hope Dies Last ..." - Cross-Sectoral Cooperation in Integrated Care]. AB - Objective Multiple models of Integrated Care (IC) have been implemented in German mental health services in the last decade in order to improve cross-sectoral, interdisciplinary cooperation. This study investigates an IC network model providing home treatment, case management and a 24/7 hotline. The aim of the study was to explore how health professionals working in this service model perceive both cooperation within their facilities and with external stakeholders. Methods 5 focus groups with 39 health professionals working in an IC mental health network were conducted and analyzed with qualitative content analysis. Results Focus groups participants reported on excellent cooperation within their facilities. The cooperation with external stakeholders, i. e. physicians, psychotherapists and psychiatric clinics, leaves room for improvement. Conclusions Until now little consideration has been given to the perspectives of health professionals. Cooperation within IC mental health networks seems to be effective. Cooperation with stakeholders outside the networks needs to be enhanced. PMID- 26859167 TI - [Medial Stigmatization of Mentally Ill Persons after the "Germanwings"-Crash]. AB - OBJECTIVE: The present study was designed to investigate the frequency of media stigmatization of mentally ill persons after the crash of the "Germanwings" aircraft on March 2015. METHOD: Evaluation of 251 texts, which were published in 12 national German newspapers. Categorical distinction between risky coverage and explicit characteristics of stigmatization. RESULTS: In 64.1 % of the evaluated texts, a psychiatric disease of the co-pilot was discussed as the possible cause of the crash, making this the most widely-used explanation in the media that we view "risky coverage". Characteristics of explicit stigmatization were found in 31.5 % of the texts. Most prominent category of explicit stigmatization was the rubric "Metaphorical language/dramatizations". It was found in 23.5 % of the articles. CONCLUSION: Predominantly risky coverage of mentally ill persons has occured in the wake of a spectacular crime. By obtaining professional expertise of psychiatrists and consistent interpretation of journalistic guidelines, unintended effects of stigmatization could be avoided in the future. PMID- 26859168 TI - Predictors of Virological Response in 3,235 Chronic HCV Egyptian Patients Treated with Peginterferon Alpha-2a Compared with Peginterferon Alpha-2b Using Statistical Methods and Data Mining Techniques. AB - Despite the appearance of new oral antiviral drugs, pegylated interferon (PEG IFN)/RBV may remain the standard of care therapy for some time, and several viral and host factors are reported to be correlated with therapeutic effects. This study aimed to reveal the independent variables associated with failure of sustained virological response (SVR) to PEG-IFN alpha-2a versus PEG-IFN alpha-2b in treatment of naive chronic hepatitis C virus (HCV) Egyptian patients using both statistical methods and data mining techniques. This retrospective cohort study included 3,235 chronic hepatitis C patients enrolled in a large Egyptian medical center: 1,728 patients had been treated with PEG-IFN alpha-2a plus ribavirin (RBV) and 1,507 patients with PEG-IFN alpha-2b plus RBV between 2007 and 2011. Both multivariate analysis and Reduced Error Pruning Tree (REPTree) based model were used to reveal the independent variables associated with treatment response. In both treatment types, alpha-fetoprotein (AFP) >10 ng/mL and HCV viremia >600 * 10(3) IU/mL were the independent baseline variables associated with failure of SVR, while male gender, decreased hemoglobin, and thyroid-stimulating hormone were the independent variables associated with good response (P < 0.05). Using REPTree-based model showed that low AFP was the factor of initial split (best predictor) of response for either PEG-IFN alpha-2a or PEG IFN alpha-2b (cutoff value 8.53, 4.89 ng/mL, AUROC = 0.68 and 0.61, P = 0.05). Serum AFP >10 ng/mL and viral load >600 * 10(3) IU/mL are variables associated with failure of response in both treatment types. REPTree-based model could be used to assess predictors of response. PMID- 26859172 TI - The Sense of Aliveness and Feelings of Being Real. AB - This is an account of a young woman who grew up with feelings of depersonalization, derealization, and lack of agency, so that she often didn't feel real or completely alive. While the psychological basis for these feelings seemed clear in her early developmental history, it was discovered that she also had major visual and psychomotor disabilities that exacerbated her situation in complicated ways. This paper touches on some of the narcissistic problems that make it difficult for the analyst to accurately view and to work holistically with issues of psyche-soma. It also suggests that actively helping the patient to perform the eye exercises that she was unable to do on her own may have been a useful parameter in this case. PMID- 26859173 TI - The Quest for Greatness in the Race to Not Be Forgotten. AB - Details from a brief psychoanalytic treatment with a disturbed and desperate patient in acute emotional crisis are used to consider the internal dread some patients have regarding separation from the object and their phantasy of eternal damnation as a result of self-differentiation. One patient's loyalty to her object as the only way to prevent abandonment is examined in depth, but also considered as a severe psychic struggle found in other disturbed patients. The nature of this pathological loyalty has to do with the internalized and projected demand for perfection as the only currency for love and acceptance. Theoretical considerations are offered from a Kleinian perspective. PMID- 26859174 TI - Ashes of Remembrance: Reconfiguring the Phoenix. AB - Literature affords the possibility of diverse perspectives, inviting the reader to try a character or experience on for size and to consider ways in which culture affects the narrative. What it means to be a person and then to become an adult within one's own ancestral tradition is inherited directly, through being with others and also through the stories that are passed along from parent to child, through which one finds one's place in the social world. Whatever the conscious intention of the author, traumatic texts are uniquely colored by the heritage that gives rise to them. Traumatic tales offer us bits and fragments from dream and fantasy, present and past, through which the reader can begin to see how meanings coalesce and cohere around signs that become symbols as we gain greater facility in reading them. In this article, I consider three threads of traumatic tales and their similarities and differences, hoping that the reader will be able to recognize both commonalities and differences, ways in which richness and texture might be added to our lives if we can recognize consciously what otherwise might haunt us. PMID- 26859175 TI - Stirred by Kafka's A Country Doctor: An Exploration of Psychoanalysts' Styles, Vulnerabilities, and Surrealistic Journeys. AB - Using Kafka's short story A Country Doctor and clinical examples as vehicles, the author demonstrates the centrality of psychoanalysts' styles and life experiences to the psychoanalytic process. Albeit charged with a distinct facilitative task, psychoanalysts inevitably bring their qualities as "fellow sufferers" (to use D. M. Orange's term) into their sessions. They experience pressures placed upon them as the "subject presumed to know," as Lacan describes. They encounter the ubiquity of self-deception, facing many unknown and unpredictable elements as they surrealistically travel through time with their patients. While understandably wanting to take refuge from their vulnerability, psychoanalysts cannot escape the influence of their individualistic and idiosyncratic natures on the transformational encounters they facilitate. PMID- 26859176 TI - A Psychoanalytic Study of Sylvia Plath. AB - Sylvia Plath's rage at her abandoning husband and at her late beloved father was partly a displacement of anger toward her loving but smothering mother. Her schizoid pathology resulting from the symbiosis (along with her bipolarity) helped prompt her suicide. At the same time her rage at the men represented a struggle to prevent it. The focus of this paper is to explore in the context of her life how the style as well as the content of her last book, Ariel, made for one long suicide note-albeit a beautifully written work of art. In the most accessible of her poems, such as "Daddy," "Lady Lazarus," and "Edge," her health overcomes her pathology. In others her pathology dominates. In Ariel Plath attempted and succeeded in turning herself into a tragic, mythic heroine, eventually drowning herself in a gas oven as she would have in the ocean-a key metaphor for her mother. PMID- 26859179 TI - m-Health: A Critical Analysis of Awareness, Perception, and Attitude of Healthcare Among Providers in Himachal Pradesh, North India. AB - INTRODUCTION: Providing healthcare in remote mountainous areas is challenging. The increasing availability of mobile connectivity needs to be exploited by offering healthcare through a mobile medium, popularly known as mobile health (m health). It is essential to understand the awareness, perception, and attitude of healthcare providers (HCPs) in deploying m-health. Their outlook on new technologies influences patient adoption. Reports on attitudes regarding healthcare through mobile phones are now confined to views from the recipient. MATERIALS AND METHODS: This study from August 1 to September 30, 2014 analyzed the views of 592 HCPs (12.3% of all HCPs) in Himachal Pradesh, India. They included faculty and students of the two medical colleges, as well as HCPs from all of the 12 districts. RESULTS: Although Himachal Pradesh has the highest teledensity of all states in India (117.6%), only 58.8% of HCPs (of those surveyed, 72% lived in suburban areas and 24.8% in Shimla, the state capital) would easily recommend m-health. Self-perceived ability to use mobile services was 85%. Fifty-nine percent used mobile devices for social networking, and 52.4% used Wi-Fi. Sixty-one percent of those interviewed were females, and 39% were males. CONCLUSIONS: The transformative potential of m-health hinges on its acceptance and use by all stakeholders. The study suggests that as HCPs in Himachal Pradesh are already using mobile value added services and are highly information technology literate, addressing their specific concerns could lead to use of m-health in Himachal Pradesh. Healthcare delivery in Himachal Pradesh is still suboptimal. With increasing connectivity, awareness, and commencement of telemedicine services in Himachal Pradesh, m-health has the potential to be a reality. PMID- 26859191 TI - Ethical Implications of Social Stigma Associated with the Promotion and Use of Pre-Exposure Prophylaxis for HIV Prevention. AB - Identifying sources of and eliminating social stigma associated with the promotion and use of pre-exposure prophylaxis (PrEP) for the prevention of sexually acquired HIV infection among men who have sex with men (MSM) is both a moral imperative and necessary requirement to ensure that public health objectives of HIV prevention can be met. This article will examine and address ethical concerns and criticisms regarding the use of PrEP, barriers to its promotion, and use among MSM and examine the types of social stigma associated with PrEP. An ethical justification for both healthcare and LGBT communities to address and overcome social stigma regarding the use of PrEP among MSM is offered. PMID- 26859192 TI - Decoding motor responses from the EEG during altered states of consciousness induced by propofol. AB - OBJECTIVE: Patients undergoing general anesthesia may awaken and become aware of the surgical procedure. Due to neuromuscular blocking agents, patients could be conscious yet unable to move. Using brain-computer interface (BCI) technology, it may be possible to detect movement attempts from the EEG. However, it is unknown how an anesthetic influences the brain response to motor tasks. APPROACH: We tested the offline classification performance of a movement-based BCI in 12 healthy subjects at two effect-site concentrations of propofol. For each subject a second classifier was trained on the subject's data obtained before sedation, then tested on the data obtained during sedation ('transfer classification'). MAIN RESULTS: At concentration 0.5 MUg ml(-1), despite an overall propofol EEG effect, the mean single trial classification accuracy was 85% (95% CI 81%-89%), and 83% (79%-88%) for the transfer classification. At 1.0 MUg ml(-1), the accuracies were 81% (76%-86%), and 72% (66%-79%), respectively. At the highest propofol concentration for four subjects, unlike the remaining subjects, the movement-related brain response had been largely diminished, and the transfer classification accuracy was not significantly above chance. These subjects showed a slower and more erratic task response, indicating an altered state of consciousness distinct from that of the other subjects. SIGNIFICANCE: The results show the potential of using a BCI to detect intra-operative awareness and justify further development of this paradigm. At the same time, the relationship between motor responses and consciousness and its clinical relevance for intraoperative awareness requires further investigation. PMID- 26859193 TI - Plasmacytoma-like Posttransplant Lymphoproliferative Disorder in a Pediatric Heart Transplant Recipient. AB - Posttransplant lymphoproliferative disorder (PTLD) is a diversely manifesting group of lymphoid or plasmacytic proliferations found in solid organ and bone marrow transplant recipients. PTLD occurs as a result of immunosuppression and is often driven by the Epstein Barr virus. Although most commonly of B-cell origin, similar to B-cell lymphomas, PTLD can rarely present as a plasmacytic process, resembling multiple myeloma. Although more common in adults, 8 cases of plasmacytoma-like PTLD have been reported in pediatric renal and combined small bowel-liver transplant recipients. Here, we present a rare report of a plasmacytoma-like PTLD case in a pediatric heart transplant recipient. PMID- 26859194 TI - Protective Effects of Isorhamnetin on Cardiomyocytes Against Anoxia/Reoxygenation induced Injury Is Mediated by SIRT1. AB - It has been reported that apoptosis plays a very important role on anoxia/reoxygenation (A/R)-induced injury, and human silent information regulator type 1 (SIRT1) can inhibit the apoptosis of cardiomyocytes. It has been proved that isorhamnetin (IsoRN), 3'-O-methyl-quecetin, can protect the cardiomyocytes, but the mechanism is still not clear. The aim of the study was to explore whether the protective effects of IsoRN on the cardiomyocytes against the A/R-induced injury are mediated by SIRT1. The effects of IsoRN on cardioprotection against A/R injury in neonatal rat cardiomyocytes were monitored by cell viability, the levels of mitochondrial membrane potential (Deltapsim), apoptosis, and intracellular reactive oxygen species (ROS), the levels of lactate dehydrogenase (LDH), creatine phosphokinase (CPK) and mitochondrial permeability transition pores (mPTP). The effects on protein expression were measured by western blot assay. The results showed that IsoRN can reduce A/R-induced injury by decreasing the level of lactate dehydrogenase and creatine phosphokinase release from the cardiomyocytes, increasing cell viability and expression of SIRT1, reducing the generation of reactive oxygen species, inhibiting opening of mitochondrial permeability transition pores and loss of Deltapsim and activation of caspase-3, and decreasing the release of cytochrome c, and reducing apoptosis. In addition, sirtinol, a SIRT1 inhibitor, drastically reduced the protective effects of IsoRN on cardioprotective effects in cardiomocytes. In conclusion, we firstly demonstrated that SIRT1 may be involved in the protective effects of IsoRN on cardiomocytes against the A/R-induced injury. PMID- 26859195 TI - CYP2J2 Overexpression Increases EETs and Protects Against HFD-Induced Atherosclerosis in ApoE-/- Mice. AB - AIMS: The aim of the present study was to investigate how cytochrome P450 (CYP)2J2-derived epoxyeicosatrienoic acids (EETs) regulate the AKT1 and FOXO1 and BIM pathway and protect against endothelial apoptosis in the development and progression of atherosclerosis. METHODS AND RESULTS: Recombinant adeno-associated virus (rAAV)-mediated CYP2J2 overexpression increased EET levels and prevented high-fat diet-induced atherosclerosis in ApoE mice, which was associated with reduced vascular apoptosis. We also observed that CYP2J2 overexpression suppressed the weight gain induced by a high-fat diet. In vitro CYP2J2 overexpression increased EET levels, subsequently preventing tumor necrosis factor-alpha-induced apoptosis in human umbilical vein endothelial cells (HUVECs), which contributed to the pathogenesis of atherosclerosis. We observed that AKT1 suppressed BIM expression and apoptosis by inhibiting the function of FOXO1 in cultured HUVECs. Furthermore, we found that CYP2J2 overexpression and its metabolic products, EETs, suppressed tumor necrosis factor-alpha-induced apoptosis through AKT1 and FOXO1 and BIM dependent signaling in HUVECs. CONCLUSIONS: In summary, we identified a novel molecular mechanism for CYP2J2 derived EETs to protect against atherosclerosis. PMID- 26859196 TI - Steroidal and Nonsteroidal Mineralocorticoid Receptor Antagonists Cause Differential Cardiac Gene Expression in Pressure Overload-induced Cardiac Hypertrophy. AB - Pharmacological blockade of mineralocorticoid receptors (MR) is known as an efficacious therapy in chronic heart failure. Therapy with steroidal MR antagonists such as spironolactone or eplerenone (EPL) is often limited because of side effects. Recently, a new highly selective and potent, nonsteroidal MR antagonist, finerenone (FIN), has been developed. To investigate the effects of FIN on pressure-induced cardiac hypertrophy, the transverse aortic constriction (TAC) model was used in C57BL/6 mice treated with FIN (10 mg.kg.d), EPL (200 mg.kg.d) or vehicle (VEH). First, we analyzed cardiac gene expression 4 weeks after TAC using a pathway-focused quantitative polymerase chain reaction array. FIN caused a distinct cardiac gene expression profile compared to VEH and EPL, including differential expression of BNP (brain natriuretic peptide) and Tnnt2 (troponin T type 2). FIN treatment led to a significant reduction of TAC-induced left ventricular (LV) wall thickening assessed by echocardiography. In accordance, FIN-treated mice showed a significant lower increase of calculated left ventricular mass compared with VEH- and EPL-treated mice (FIN: 28.4 +/- 3.7 mg; EPL: 38.4 +/- 4.3 mg; VEH: 39.3 +/- 3.1 mg; P < 0.05). These data show beneficial effects of nonsteroidal MR antagonism by FIN on left ventricular mass development in pressure overload associated with a distinct cardiac gene expression profile. PMID- 26859197 TI - Saikosaponin-a Attenuates Oxidized LDL Uptake and Prompts Cholesterol Efflux in THP-1 Cells. AB - Saikosaponins-a (Ssa) is a major bioactive extract of Radix Bupleuri which is a traditional Chinese medicine. The roles of inflammatory response and lipid transportation in the process of atherosclerosis have drawn increasing attention. We explored the regulation of lipid transportation and immune-inflammatory role of Ssa in early atherosclerosis. The antiatherogenic actions and possible molecular mechanisms of Ssa were texted in THP-1 cells. We examined the effect of Ssa on oxidized low-density lipoprotein (ox-LDL)-induced lipid uptake, cholesterol efflux, immune-inflammatory response. THP-1 macrophages were treated with Ssa followed by ox-LDL for 24 hours. Results from western blot showed that Ssa obviously reduced lipoprotein uptake to block foam cell formation and the expression of Density Lipoprotein Receptor-1 and CD36. Ssa also significantly boosted cholesterol efflux and the expression of ATP binding cassettetransporter A1 and peroxisome proliferator-activated receptor gamma. The results also indicated that Ssa inhibited ox-LDL-induced activation of AKT and nuclear factor kappaB, assembly of NLRP3 inflammasome and production of proinflammatory cytokines. It is suggested that the ability against immune inflammatory response of Ssa is due to modulation of the PI3K/AKT/NF-kappaB/NLRP3 pathway. In conclusion, this study provides new insight into Ssa's molecular mechanism and its therapeutic potential in the treatment of atherosclerosis. PMID- 26859198 TI - Rutaecarpine Reverses the Altered Connexin Expression Pattern Induced by Oxidized Low-density Lipoprotein in Monocytes. AB - Adhesion of monocytes to the vascular endothelium is crucial in atherosclerosis development. Connexins (Cxs) which form hemichannels or gap junctions, modulate monocyte-endothelium interaction. We previously found that rutaecarpine, an active ingredient of the Chinese herbal medicine Evodia, reversed the altered Cx expression induced by oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells, and consequently decreases the adhesive properties of endothelial cells to monocytes. This study further investigated the effect of rutaecarpine on Cx expression in monocytes exposed to ox-LDL. In cultured human monocytic cell line THP-1, ox-LDL rapidly reduced the level of atheroprotective Cx37 but enhanced that of atherogenic Cx43, thereby inhibiting adenosine triphosphate release through hemichannels. Pretreatment with rutaecarpine recovered the expression of Cx37 but inhibited the upregulation of Cx43 induced by ox-LDL, thereby improving adenosine triphosphate-dependent hemichannel activity and preventing monocyte adhesion. These effects of rutaecarpine were attenuated by capsazepine, an antagonist of transient receptor potential vanilloid subtype 1. The antiadhesive effects of rutaecarpine were also attenuated by hemichannel blocker 18alpha-GA. This study provides additional evidence that rutaecarpine can modulate Cx expression through transient receptor potential vanilloid subtype 1 activation in monocytes, which contributes to the antiadhesive properties of rutaecarpine. PMID- 26859200 TI - A Validated Method for Quantification of Dolutegravir Using Ultra Performance Liquid Chromatography Coupled With UV Detection. AB - BACKGROUND: Dolutegravir (DTG) is an integrase strand transfer inhibitor, which is a newly approved antiretroviral drug used for the treatment of HIV-infected naive and experienced individuals. Many aspects of DTG pharmacology remain to be studied. Our aim was to develop and fully validate a robust analytical method for the quantification of DTG in plasma using liquid chromatography coupled with UV detection. METHODS: A simple and rapid protein precipitation method was used for analyte extraction from 100 uL plasma. The separation was achieved on a C8 reverse-phase analytical column using a gradient elution with 50 mmol/L formic acid and 50 mmol/L ammonium acetate in water (mobile phase A), and 100% acetonitrile (mobile phase B) and at a flow rate of 0.3 mL/min and a total run time of 10 minutes. The detector wavelength was set at 258 nm. RESULTS: The linearity of the calibration curve (r > 0.9999, n = 6) was validated over a concentration range of 0.25-10 mcg/mL. Intra-assay variability ranged from 3.3% to 6.1% and inter-assay variability ranged from 4.5% to 5.7%. The overall accuracy ranged from 90.7% to 97.7% for the 3 different concentrations of quality control samples. Recovery efficiency of extraction ranged from 94.3%-100%. This method is highly selective with no interferences from commonly concomitant antiretroviral drugs or endogenous metabolites. CONCLUSIONS: The described method is simple, robust, selective, accurate, precise, and cost-effective. Thus, this assay can be readily transferred and implemented in clinical settings and used for pharmacokinetic studies and therapeutic drug monitoring programs. PMID- 26859199 TI - Endocytosis and Endosomal Trafficking of DNA After Gene Electrotransfer In Vitro. AB - DNA electrotransfer is a successful technique for gene delivery into cells and represents an attractive alternative to virus-based methods for clinical applications including gene therapy and DNA vaccination. However, little is currently known about the mechanisms governing DNA internalization and its fate inside cells. The objectives of this work were to investigate the role of endocytosis and to quantify the contribution of different routes of cellular trafficking during DNA electrotransfer. To pursue these objectives, we performed flow cytometry and single-particle fluorescence microscopy experiments using inhibitors of endocytosis and endosomal markers. Our results show that ~50% of DNA is internalized by caveolin/raft-mediated endocytosis, 25% by clathrin mediated endocytosis, and 25% by macropinocytosis. During active transport, DNA is routed through multiple endosomal compartments with, in the hour following electrotransfer, 70% found in Rab5 structures, 50% in Rab11-containing organelles and 30% in Rab9 compartments. Later, 60% of DNA colocalizes with Lamp1 vesicles. Because these molecular markers can overlap while following organelles through several steps of trafficking, the percentages do not sum up to 100%. We conclude that electrotransferred DNA uses the classical endosomal trafficking pathways. Our results are important for a generalized understanding of gene electrotransfer, which is crucial for its safe use in clinics. PMID- 26859201 TI - Lung Metastasis From Prostate Cancer Revealed by 18F-FDG PET/CT Without Osseous Metastasis on Bone Scan. AB - A 54-year-old man, a case of prostate cancer, underwent radical prostatectomy and hormone therapy. Elevated prostate-specific antigen level developed 7 years later, but pelvic MRI and bone scan revealed negative results. Radiotherapy was performed under the suspicion of local recurrence but in vain. F-FDG PET/CT performed 1 more year later showed 3 FDG-avid lesions in the right lung and mediastinum. Lung and lymph node metastases were proved with video-assisted thoracoscopic surgery. Bone scan remained negative at that time. PMID- 26859202 TI - Dynamic Scintigraphy With SPECT-CT of Postoperative Salivary Leak. AB - This 65 year-old woman, 1 month postoperative after maxillary sinus carcinoma (pT4N0cM0) excision and reconstruction, presented with significant left facial clear fluid wound leakage. A salivary or cerebrospinal leakage was suspected. Fluid analysis, CT, and MRI were noncontributory. Dynamic salivary scintigraphy with SPECT-CT allowed for the detection and localization of the leakage from the left parotid gland. Radioactive dose rate of the wound bandage was 50 MUSv/h compared with 0.05 MUSv/h for background and confirmed the diagnosis. Left total parotidectomy resulted in resolution. PMID- 26859203 TI - Klippel-Feil Syndrome With Spinal Dysraphism: Diastematomyelia on 18F-NaF Bone PET, CT, and MRI Imaging. AB - A 49-year-old woman with known Klippel-Feil syndrome had a CT scan for staging of stage IIIA invasive carcinoma of the left breast. She was found to have cervicothoracic spinal dysraphism with diastematomyelia. An F-NaF bone PET done as part of the metastatic workup showed the characteristic sagittal bone spur, and MRI demonstrated a complete split of the cervical and upper thoracic spinal cord, previously unknown to the patient. PMID- 26859204 TI - Solitary Plasmacytoma in the Renal Pelvis on 18F-FDG and 11C-Acetate PET/CT. AB - A 70-year-old man was incidentally found to have an occupying lesion in the left renal pelvis by ultrasonography during a routine health examination. CT images suggested renal cell carcinoma. FDG PET/CT scan was acquired for staging. The images did not reveal any hypermetabolic metastases. However, the metabolic activity of the lesion in the right renal pelvis was not unambiguously determined because of interference of radioactive urine. C-acetate PET/CT, on the other hand, clearly revealed increased activity in the left renal pelvis. Pathological examination demonstrated solitary extraosseous plasmacytoma. PMID- 26859205 TI - 68Ga Prostate-Specific Membrane Antigen Uptake in Renal Cell Cancer Lymph Node Metastases. AB - Ga prostate-specific membrane antigen (PSMA)-HBED-CC PET/CT in a patient with a history of both prostate cancer (PC) and renal cell cancer (RCC) shows high PSMA expression in the residual right seminal vesicle suggestive of local recurrence of PC as well as suspected PSMA-positive mediastinal, retroperitoneal, and iliac lymph nodes. Regarding the latter, biopsy revealed lymph node metastases from RCC excluding PC metastases. This case exemplarily demonstrates that high PSMA expression in RCC metastases can potentially mimic PC metastases. Thus, for accurate interpretation of imaging results in PC patients with additional primary tumors, knowledge of PSMA expression of non-PC tissue is necessary. PMID- 26859206 TI - Quality and Safety in Health Care, Part IX: Computerized Provider Order Entry. AB - One of the most important technologic advances to reduce medication errors is computerized provider order entry linked with clinical decision support. These systems also have the potential to improve the adherence of clinicians to best practices, decrease the turnaround time for laboratory tests and radiology examinations, speed transmission of prescriptions to the pharmacy, decrease medication costs, and increase the frequency of vaccinations. PMID- 26859207 TI - Mammillary Body: Chronic Refractory Epilepsy Seizure Focus Detected by 18F-FDG PET-CT. AB - Epilepsy is one of the most common neurological conditions, which affect nearly 1% of the entire population. We present F-FDG PET-CT findings of a mammillary body epileptic focus in a 50-year-old woman with a 5-year history of seizure and behavior disturbance and memory problems for the past 4 years. PMID- 26859208 TI - Glioma Recurrence Versus Radiation Necrosis: Single-Session Multiparametric Approach Using Simultaneous O-(2-18F-Fluoroethyl)-L-Tyrosine PET/MRI. AB - PURPOSE: This study aimed to investigate the potential of hybrid gadolinium (Gd) enhanced F-fluoroethyl-L-tyrosine (F-FET) PET/MRI in distinguishing recurrence from radiation necrosis using simultaneously acquired multiple structural and functional parameters. METHODS: Twenty-six patients (5 female and 21 male patients; mean +/- SD age, 51.58 +/- 15.97 years) with single or multiple contrast-enhancing brain lesions (n = 32) on MRI after surgery and radiation therapy were evaluated with simultaneously acquired Gd-enhanced F-FET PET/MRI. They were then followed up with resurgery and histopathological diagnosis (n = 9) and/or clinical/MRI- or PET/MRI-based imaging follow-up (n = 17). PET/MR images were analyzed using manually drawn regions of interest over areas of maximal contrast enhancement and/or FET uptake. Maximum target-to-background ratio (TBRmax), mean target-to-background ratio (TBRmean), and choline-to-creatine (Cho/Cr) ratios as well as normalized mean relative cerebral blood volume (rCBVmean) and mean apparent diffusion coefficient (ADCmean) were determined. The accuracy of each parameter individually and in various possible combinations for differentiating recurrence versus radiation necrosis was evaluated using 2-tailed independent samples Student t test, multivariate analysis of variance, and multivariate receiver operating characteristic analysis. Positive histopathological finding and long-term imaging/clinical follow-up suggestive of disease progression served as criterion standard. RESULTS: Of 26 patients, 19 were classified as recurrence, with 7 patients showing radiation necrosis. Individually, TBRmax, TBRmean, ADCmean, and Cho/Cr ratios as well as normalized rCBVmean was significant in differentiating recurrence from radiation necrosis, with an accuracy of 93.8% for TBRmax, 87.5% for TBRmean, 81.3% for ADCmean, 96.9% for Cho/Cr ratio, and 90.6% for normalized rCBVmean. The accuracy of both normalized rCBVmean and ADCmean was improved in combination with TBRmax or Cho/Cr ratio. However, TBRmax (or TBRmean) with Cho/Cr ratio yielded the highest accuracy, approaching up to 97%. Furthermore, maximum area under the curve is achieved with the combination of TBRmean, CBV, and Cho/Cr values. CONCLUSIONS: Our findings suggest that FET uptake with Cho/Cr ratio and normalized rCBVmean could be most useful to distinguish primary glioma recurrence from radiation necrosis. Hybrid simultaneous multiparametric F-FET PET/MRI might play a significant role in the evaluation of patients with suspected glioma recurrence. PMID- 26859209 TI - Detection of Sarcomatoid Lung Metastasis With 68GA-PSMA PET/CT in a Patient With Prostate Cancer. AB - A 70-year-old man with prostate cancer (adenocarcinoma; pT3aN0Mx; GS: 4 + 4) underwent radical prostatectomy and lymph node dissection in February 2008. In December 2009, biochemical recurrence occurred and prostate-specific antigen progressively increased to 4.63 ng/mL despite local salvage radiotherapy and androgen deprivation. Ga-PSMA PET/CT showed a positive left iliac lymph node and a pathological left pulmonary lesion, which was highly positive in a subsequent F FDG PET/CT. Lymph node resection confirmed an adenocarcinoma metastasis of the prostate cancer and lung surgery demonstrated a sarcomatoid metastasis of prostate cancer. After surgery, prostate-specific antigen decreased to 0.03 ng/mL. PMID- 26859210 TI - Early Dynamic 68Ga-DOTA-D-Phe1-Tyr3-Octreotide PET/CT in Patients With Hepatic Metastases of Neuroendocrine Tumors. AB - BACKGROUND AND AIMS: Whole-body PET with Ga-DOTA-D-Phe-Tyr-octreotide (Ga DOTATOC) and contrast-enhanced CT (ceCT) are considered a standard for the staging of neuroendocrine tumors (NETs). This study sought to verify whether early dynamic (ed) Ga-DOTATOC PET/CT can reliably detect liver metastases of NETs (hypervascular, nonhypervascular; positive or negative for somatostatin receptors) and to verify if the receptor positivity has a significant impact on the detection of tumor hypervascularization. METHODS: Twenty-seven patients with NET were studied by ceCT and standard whole-body PET according to established Ga DOTATOC protocols. In addition, edPET data were obtained by continuous scanning during the first 300 seconds after bolus injections of the radiotracer. Early dynamic PET required an additional low-dose, native CT image of the liver for the purpose of attenuation correction. Time-activity and time-contrast curves were obtained, the latter being calculated by the difference between tumor and reference regions. RESULTS: Early dynamic PET/CT proved comparable with ceCT in readily identifying hypervascular lesions, irrespective of the receptor status, with activities rising within 16 to 40 seconds. Early dynamic PET/CT also readily identified nonhypervascular, receptor-positive lesions. Positive image contrasts were obtained for hypervascular, receptor-positive lesions, whereas early negative contrasts were obtained for nonhypervascular, receptor-negative lesions. CONCLUSIONS: The high image contrast of hypervascular NET metastases in early arterial phases suggests that edPET/CT can become a useful alternative in patients with contraindications to ceCT. The high density of somatostatin receptors did not seem to interfere with the detection of the lesion's hypervascularization. PMID- 26859211 TI - Plasma Glucose Levels Affect Cerebral 18F-FDG Distribution in Cognitively Normal Subjects With Diabetes. AB - PURPOSE: Increased plasma glucose levels can relatively reduce F-FDG uptake in Alzheimer disease (AD)-related regions and alter the cerebral distribution pattern of F-FDG, resulting in the appearance of an AD-like pattern. However, the relationship between the reversibility of the AD-like pattern and plasma glucose levels is uncertain. METHODS: Four cognitively normal elderly subjects with diabetes underwent longitudinal F-FDG PET more than 5 times at various levels of plasma glucose. F-FDG data were proportionally scaled with a global normalization method and used in volume of interest-based and voxelwise analyses. Volumes of interest were placed on representative AD-related regions: precuneus/posterior cingulate (PP), lateral parietal cortex, and frontal cortex. RESULTS: Volume of interest-based analyses showed negative correlations of plasma glucose levels with F-FDG uptake in the PP (r = -0.79, P < 0.001), lateral parietal cortex (r = 0.62, P = 0.002), and frontal cortex (r = -0.73, P < 0.001), controlling for the effects of interindividual differences and age. Voxelwise analyses also showed negative correlations between the 2 factors in the PP and medial frontal areas (P < 0.05, familywise error rate corrected). CONCLUSIONS: This study indicates that the distribution pattern of F-FDG changes depending on plasma glucose levels in an individual and that the AD-like pattern can appear or disappear with increasing or decreasing plasma glucose levels, respectively. PMID- 26859212 TI - Evaluation of Time-Phase Effect on 18F-FDG PET/CT Delineation Methods for Treatment Planning of Nasopharyngeal Carcinoma. AB - PURPOSE: Tumor boundary delineation using F-FDG PET/CT is a promising tool for radiotherapy applications, but no consensus has been established regarding the optimal delineation method. Time-phase variability of F-FDG PET/CT imaging frequently affects metabolically active volumes and treatment planning for nasopharyngeal carcinoma (NPC). This study aimed to evaluate the time-phase robustness of 8 methods commonly used for tumor volume delineation in NPC. PATIENTS AND METHODS: Twenty patients with biopsy-proven NPC were included and underwent multiple time-phase F-FDG PET/CT imaging. Gross tumor volumes (GTVs), absolute SUV, gradient-based watershed segmentation (GTV-GWT), and anatomic biologic contouring (GTV-ABC) values were determined. The volume of overlap between GTV-CT and the 8 PET-based GTVs was enclosed and the overlap fraction (OF CT) calculated. Color matrix was used to semiquantify the time-phase differences. Gross tumor volume values obtained with different methods were recorded and compared using paired t test. Time-phase differences of GTVs and SUVmax were compared among groups by analysis of variance with Tukey honest significance tests. The coefficients of variation were computed to assess intrapatient time phase variability. Similarity coefficient was calculated to evaluate similarity. RESULTS: Differences were observed between GTVs obtained at different time points using various delineation procedures. Nonsignificantly higher percentages were obtained for GTV-GWT (88.17%) and GTV-ABC (86.98%) compared with other methods, showing their robustness. GTV-40% (0.81-0.88) and GTV-ABC (0.82-0.88) indicated higher similarity with GTV-MRI than the other methods. CONCLUSIONS: PET/CT-based GTV-ABC between 35 and 55 minutes should be the first choice for NPC treatment planning. PMID- 26859213 TI - 68Ga-Labeled Anti-Prostate-Specific Membrane Antigen Peptide as Marker for Androgen Deprivation Therapy Response in Prostate Cancer. AB - Prostate cancer was diagnosed in a 71-year-old man with an elevated prostate specific antigen. The CT of the abdomen showed multiple para-aortal lymph nodes, and thus, a Ga anti-prostate-specific membrane antigen (PSMA-11) PET/CT was initiated, which showed, aside from the prostate cancer and multiple iliacal and para-aortal lymph node metastases, an increased tracer uptake in a lymph node left cervical. According to this advanced disease, a palliative therapy with GnRH agonist was initiated. A second PSMA-11 PET/CT was performed 4 months later, which showed a very good response; thus, additional radiation of the pelvis and the draining lymphatic system was performed. PMID- 26859214 TI - Chilaiditi Sign on 99mTc-Mebrofenin Hepatobiliary Scan Mimicking Bile Leak in Acute Cholecystitis. AB - Chilaiditi sign is the incidental radiologic finding of intestinal interposition between the liver and diaphragm, whereas Chilaiditi syndrome describes the presence of accompanying clinical symptoms including abdominal pain, constipation, vomiting, and respiratory distress. We describe a case of radiotracer accumulation over the liver dome on Tc-mebrofenin hepatobiliary scan performed on a 72-year-old man with acute cholecystitis mimicking a bile leak. However, chest radiograph and CT revealed intestinal hepatodiaphragmatic interposition. This case illustrates the importance of being familiar with the scintigraphic appearance of the Chilaiditi sign and correlating abnormal nuclear medicine scan findings with other available radiologic modalities. PMID- 26859215 TI - FDG PET/CT of Intercostal Schwannoma. AB - Intercostal schwannoma is rare. We report FDG PET/CT findings of intercostal schwannoma in a 66-year-old woman. The tumor contains both solid and cystic components with intense FDG activity in the solid component. Postsurgical pathology diagnosis revealed schwannoma. PMID- 26859216 TI - Imaging Pediatric Plasmacytoid Dendritic Cell Neoplasm With FDG PET/CT: Atypical Presentation of a Rare Disease. AB - Blastic plasmacytoid dendritic cell neoplasm is a rare malignancy characterized by cutaneous involvement and hematological dissemination. Most affected patients are older, usually in the sixth or seventh decade of life, and this condition has rarely been described in the pediatric population. This report presents the case of a 9-year-old boy with blastic plasmacytoid dendritic cell neoplasm and demonstrates the utility of FDG PET/CT for staging and treatment follow-up. PMID- 26859217 TI - FDG PET/CT in Sarcomatoid Carcinoma of the Gallbladder With Chondroid Differentiation. AB - Sarcomatoid carcinoma of the gallbladder, composed of epithelial and sarcomatous components, is a rare malignant tumor with a poor prognosis. A 61-year-old man was admitted because of abdominal distention for 2 weeks. Enhanced CT showed a large gallbladder tumor with central necrosis. The tumor measuring 18 cm in maximum diameter showed intense peripheral FDG uptake with SUVmax of 15.4. The specimen of the resected tumor revealed tubular adenocarcinoma and sarcomatoid tissue with chondroid differentiation. Immunohistochemical staining showed the sarcomatoid tissue was positive for EMA, CD10, and VIM, with proliferation index of 80%. These pathologic findings were consistent with sarcomatoid carcinoma. PMID- 26859218 TI - Potential Applications of Using 68Ga-Evans Blue PET/CT in the Evaluation of Lymphatic Disorder: Preliminary Observations. AB - PURPOSE: Potentials of 68Ga-NEB as a PET tracer in the evaluation of a variety of lymphatic drainage disorders were analyzed. METHODS: 68Ga-NEB was injected subcutaneously, and the PET/CT images were acquired in 13 patients with different suspected lymphatic drainage abnormality. The 68Ga-NEB PET/CT findings were compared with Tc-SC lymphoscintigraphy. RESULTS: 68Ga-NEB activity could be clearly observed in the lymphatic route on the PET/CT images from all the patients. In 5 (38.5%) of 13 patients tested, 68Ga-NEB PET/CT provided more information than the Tc-SC lymphoscintigraphy. CONCLUSIONS: 68Ga-NEB PET/CT can be used as an alternative of Tc-SC lymphoscintigraphy in the evaluation of lymphatic disorders, which enables fast results and might be more accurate than the conventional Tc-SC lymphoscintigraphy. PMID- 26859219 TI - Fusion FDG-PET/MRI Evidence to Support Diagnosis of Frontotemporal Dementia Related Primary Progressive Aphasia. AB - A 61-year-old right-handed man presented for cognitive neurological evaluation with word-finding difficulty, impaired word retrieval, impaired repetition of phrases, and stammering. Brain MRI and FDG-PET/CT were performed as initial imaging workup. Further FDG PET/MRI brain images were obtained through software fusion and revealed regional cortical atrophy with corresponding hypometabolic activity involving the posterior aspects of the left middle and inferior temporal gyri. These characteristic imaging findings are supportive of patient's diagnosis of frontotemporal dementia-related primary progressive aphasia. PMID- 26859220 TI - Prehabilitation in our most frail surgical patients: are wearable fitness devices the next frontier? AB - PURPOSE OF REVIEW: Frailty is the concept of accumulating physiologic declines that make people less able to deal with stressors, including surgery. Prehabilitation is intervention to enhance functional capacity before surgery. Frailty and prehabilitation among transplant populations and the role of wearable fitness tracking devices (WFTs) in delivering fitness-based interventions will be discussed. RECENT FINDINGS: Frailty is associated with increased complications, longer length of hospital stay and increased mortality after surgery. Frail kidney transplant patients have increased delayed graft function, mortality and early hospital readmission. Frail lung or liver transplant patients are more likely to delist or die on the waitlist. Prehabilitation can mitigate frailty and has resulted in decreased length of hospital stay and fewer postsurgical complications among a variety of surgical populations. Increasingly, WFTs are used to monitor patient activity and improve patient health. Interventions using WFTs have resulted in improved activity, weight loss and blood pressure. SUMMARY: Frailty is a measurable parameter that identifies patients at risk for worse health outcomes and can be mitigated through intervention. Prehabilitation to reduce frailty has been shown to improve postsurgical outcomes in a variety of populations. WFTs are being integrated in healthcare delivery for monitoring and changing health behavior with promising results. PMID- 26859221 TI - The role of biologicals in intestinal transplantation. AB - PURPOSE OF REVIEW: This article reviews the role of biologicals in intestinal transplantation. RECENT FINDINGS: Several biologicals have been used in intestinal and multivisceral transplantation for various indications, such as induction therapy, prevention and treatment of antibody-mediated rejection, desensitization, anti-inflammatory treatment, as well as treatment of Epstein Barr virus-associated posttransplant lymphoproliferative disease. Particularly, the administration of biologicals in induction therapy such as T-cell depleting antibodies and interleukin-2 receptor antagonists have significantly contributed to the great improvement of patient and allograft outcome. Novel biologicals, such as B-cell, plasma-cell, and complement-directed agents have been successfully applied to treat antibody and complement-driven alloimmune processes to stabilize long-term outcome. Several other inflammatory allotransplant conditions have been addressed with anti-TNF-alpha antibodies, such as infliximab. SUMMARY: Biologicals have contributed significantly to the recent success of intestinal transplantation. Novel developments in this field are supposed to aid in addressing various urgent needs in intestinal transplantation, such as preimmunization, antibody and complement-induced graft injury, as well as pathologies originating from innate immune responses. PMID- 26859222 TI - Liver transplantation and hepatitis B virus infection: towards an immunoglobulin free antiviral treatment after transplantation. AB - PURPOSE OF REVIEW: This article provides an update on the latest development on deploying oral nucleosides in an immunoglobulin-free regime against hepatitis B virus (HBV) recurrence after liver transplantation. RECENT FINDINGS: Entecavir and tenofovir are the two newer oral nucleosides that are associated with a low virological rebound rate at less than 2% at 5 years. As a result, they have been applied as standalone treatment against HBV recurrence after liver transplantation without immunoglobulin. Recent evidence has shown that a hepatitis B surface antigen seroclearance rate of 86% and 91% after 1 and 2 years was achievable with entecavir monotherapy. Moreover, none of the patients had histological graft damage because of HBV recurrence and an overall survival over 80% at 7 years has been reported. SUMMARY: With newer and more potent oral nucleos(t)ide (NA) available, a hepatitis B immune globulin-free regimen after liver transplantation has become safe and feasible for suppression of HBV recurrence after liver transplantation, and for avoidance of HBV-related graft complications. PMID- 26859224 TI - Synthesis and optical property characterization of elongated AuPt and Pt@Au metal nanoframes. AB - We report a facile method to synthesize elongated nanoframes consisting of Pt and Au in solution. Pentagonal Au nanorods served as templates and successfully led to an elongated AuPt nanoframe after etching the core Au. Subsequently, the coating of Au around Pt ridges resulted in Pt@Au metal nanoframes. The resulting elongated nanostructure exhibited 5 well-defined ridges continuously connected along the long axis. During the shape evolution from pure Au nanorods to elongated Pt@Au metal nanoframes, their corresponding localized surface plasmon resonance bands were monitored. Especially, unique surface plasmon features were observed for elongated Pt@Au nanoframes where the short-axis oscillation of surface free electrons is strongly coupled but the long-axis oscillation is not coupled among the ridges. PMID- 26859223 TI - Hospital revascularisation capability and quality of care after an acute coronary syndrome in Switzerland. AB - BACKGROUND: Patients with acute coronary syndrome (ACS) transferred to regional nonacademic hospitals after percutaneous coronary intervention (PCI) may receive fewer preventive interventions than patients who remain in university hospitals. We aimed at comparing hospitals with and without PCI facilities regarding guidelines-recommended secondary prevention interventions after an ACS. METHODS: We studied patients with ACS admitted to a university hospital with PCI facilities in Switzerland, and either transferred within 48 hours to regional nonacademic hospitals without PCI facilities or directly discharged from the university hospital. We measured prescription rates of evidence-based recommended therapies after ACS including reasons for nonprescription of aspirin, statins, beta-blockers, angiotensin converting-enzyme inhibitors (ACEI) / angiotensin II receptor blockers (ARB), along with cardiac rehabilitation attendance and delivery of a smoking cessation intervention. RESULTS: Overall, 720 patients with ACS were enrolled; 541 (75.1%) were discharged from the hospital with PCI facilities, 179 (24.9%) were transferred to hospitals without PCI facilities. Concomitant prescription of aspirin, beta-blockers, ACEI/ARB and statins at discharge was similar in hospitals with and without PCI facilities, reaching 83.9% and 85.5%, respectively (p = 0.62). Attendance at cardiac rehabilitation reached 55.5% for the hospital with PCI facilities and 65.7% for hospitals without PCI facilities (p = 0.02). In-hospital smoking cessation interventions were delivered to 70.8% patients exclusively at the hospital with PCI facilities. CONCLUSION: Quality of care for patients with ACS discharged from hospitals without PCI facilities was similar to that of patients directly discharged from the hospital with PCI facilities, except for in-hospital smoking cessation counselling and cardiac rehabilitation attendance. PMID- 26859225 TI - Overactive bladder and autonomic dysfunction: Lower urinary tract symptoms in females with postural tachycardia syndrome. AB - AIMS: Postural Tachycardia Syndrome (POTS) represents an autonomic disorder predominantly affecting females between 15 and 50 years of age. POTS is a chronic disorder (>6 months) characterized by an excessive heart rate increment on standing (>30 beats/min) in the presence of characteristic symptoms of cerebral hypoperfusion or sympathetic activation. Patients have clinically been noted to describe lower urinary tract symptoms (LUTS), although urologic symptoms have not been methodically assessed in the POTS population. Herein, we present data from a pilot study designed to identify and quantitate overactive bladder (OAB) in patients diagnosed with POTS. METHODS: Patients admitted to the Vanderbilt Autonomic Dysfunction Center between June 2009 and October 2010 for evaluation for the potential diagnosis of POTS completed a validated, standardized questionnaire for OAB (OAB-q) at presentation. Symptom score and subscale analyses were conducted. Subscale health related quality of life (HRQL) scores were transformed into a 0-100 scale, with higher scores reflecting superior HRQL. Data are presented as mean +/- SD. RESULTS: Thirty-two females presented for evaluation of symptoms consistent with POTS. Twenty-nine women were subsequently diagnosed with POTS with 19 of these patients completing the OAB-q questionnaire (65.5% response rate). Average age was 33.5 +/- 8.3 years. Symptom severity transformed score was 26.0 +/- 16.4, with 13 of 19 patients (68.4%) meeting clinical criteria for diagnosis of probable clinically significant OAB. Nocturia was the most bothersome symptom, followed by increased daytime frequency and urgency. CONCLUSIONS: This pilot study describes bothersome lower urinary tract dysfunction in patients presenting with POTS as assessed by patient-reported questionnaire data. Nocturia demonstrated the greatest negative impact on health related quality of life (HRQL), while social interaction was the least affected HRQL domain. In patients with dysautonomia, this data provides a critical baseline for mechanistic insight into both disease-specific and global pathophysiology of nocturia and OAB. Neurourol. Urodynam. 36:610-613, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26859227 TI - Evolution of behavioural and cellular defences against parasitoid wasps in the Drosophila melanogaster subgroup. AB - It may be intuitive to predict that host immune systems will evolve to counter a broad range of potential challenges through simultaneous investment in multiple defences. However, this would require diversion of resources from other traits, such as growth, survival and fecundity. Therefore, ecological immunology theory predicts that hosts will specialize in only a subset of possible defences. We tested this hypothesis through a comparative study of a cellular immune response and a putative behavioural defence used by eight fruit fly species against two parasitoid wasp species (one generalist and one specialist). Fly larvae can survive infection by melanotically encapsulating wasp eggs, and female flies can potentially reduce infection rates in their offspring by laying fewer eggs when wasps are present. The strengths of both defences varied significantly but were not negatively correlated across our chosen host species; thus, we found no evidence for a trade-off between behavioural and cellular immunity. Instead, cellular defences were significantly weaker against the generalist wasp, whereas behavioural defences were similar in strength against both wasps and positively correlated between wasps. We investigated the adaptive significance of wasp induced oviposition reduction behaviour by testing whether wasp-exposed parents produce offspring with stronger cellular defences, but we found no support for this hypothesis. We further investigated the sensory basis of this behaviour by testing mutants deficient in either vision or olfaction, both of which failed to reduce their oviposition rates in the presence of wasps, suggesting that both senses are necessary for detecting and responding to wasps. PMID- 26859226 TI - Targeted deletion of miR-139-5p activates MAPK, NF-kappaB and STAT3 signaling and promotes intestinal inflammation and colorectal cancer. AB - miR-139-5p, which has been reported to be underexpressed in several types of cancer, is associated with tumorigenesis by participating in various biological processes via the modulation of different target genes. In the present study, we analyzed mice deficient in miR-139-5p, aiming to investigate its role in intestinal inflammation and colitis-associated colorectal cancer. We show that miR-139-5p knockout (KO) mice are highly susceptible to colitis and colon cancer, accompanied by elevated proliferation and decreased apoptosis, as well as an increased production of inflammatory cytokines, chemokines and tumorigenic factors. Furthermore, enhanced colon inflammation and colorectal tumor development in miR-139-5p KO mice are a result of the regulatory effects of miR 139-5p on its target genes for Rap1b and nuclear factor-kappa B, thus affecting the activity of the mitogen-activated protein kinase, nuclear factor-kappa B and signal transducer and activator of transcription 3 signaling pathways. These results reveal a critical part for miR-139-5p in maintaining intestinal homeostasis and protecting against colitis and colorectal cancer in vivo, providing new insights into the function of miR-139-5p with respect to linking inflammation to carcinogenesis. PMID- 26859228 TI - Individual Therapy With a Child of Divorced Parents. AB - This article reviews the literature on divorce as a risk factor in children's psychological development; describes common themes expressed by children presenting in treatment; and highlights the unique challenges for the child therapist working with a child of divorce, particularly those with high parental conflict and court involvement. Then, using a case example, the article describes therapeutic strategies and a treatment structure that, consistent with the ethical guidelines of the American Psychological Association (2010), focuses on developing and maintaining the therapeutic relationship to support the psychological growth of the child. Finally, the article discusses the ethical challenges inherent in providing therapeutic intervention for this type of child and the implications for this type of therapeutic approach. PMID- 26859229 TI - First trimester human placenta prevents breast cancer cell attachment to the matrix: The role of extracellular matrix. AB - The extracellular matrix (ECM) affects cancer cell characteristics. Its detachment from the ECM induces cell apoptosis, termed anoikis. Cancer cells can develop anoikis resistance, a necessary step for metastasis, by switching integrins, over-expressing growth factor receptors, and inducing epithelial mesenchymal transition (EMT). The placenta is a non-supportive microenvironment for cancer cells. We showed that breast cancer cells (BCCL) were eliminated from placental implantation sites. During implantation, the placenta manipulates its surrounding matrix, which may induce BCCL elimination. Here, we explored the effect of placenta-induced ECM manipulations on BCCL. During experiments, BCCL (MCF-7/T47D) were cultured on placenta/BCCL-conditioned ECM (Matrigel used for first trimester placenta/BCCL culture and cleared by NH4 OH). After culturing the cells, we analyzed cancer cell phenotype (death, count, aggregation, MMP) and signaling (microarray analysis and pathway validation). We found that the BCCL did not attach to previous placental implantation sites and instead, similarly to anoikis-resistant cells, migrated away, displayed increased MMP levels/activity, and formed aggregates in distant areas. T47D were less affected than the MCF-7 cells, since MCF-7 also showed modest increases in cell death, EMT, and increased proliferation. Microarray analysis of the MCF-7 highlighted changes in the integrin, estrogen, EGFR, and TGFbeta pathways. Indeed, placental ECM reduced ERalpha, induced Smad3/JNK phosphorylation and increased integrin-alpha5 expression (RGD-dependent integrin) in the BCCL. Addition of RGD or TGFbetaR/JNK inhibitors reversed the phenotypic changes. This study helps explain the absence of metastases to the placenta and why advanced cancer is found in pregnancy, and provides possible therapeutic targets for anoikis-resistant cells. (c) 2016 Wiley Periodicals, Inc. PMID- 26859230 TI - Modulating Antimicrobial Activity and Mammalian Cell Biocompatibility with Glucosamine-Functionalized Star Polymers. AB - The development of novel reagents and antibiotics for combating multidrug resistance bacteria has received significant attention in recent years. In this study, new antimicrobial star polymers (14-26 nm in diameter) that consist of mixtures of polylysine and glycopolymer arms were developed and were shown to possess antimicrobial efficacy toward Gram positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) (with MIC values as low as 16 MUg mL(-1)) while being non hemolytic (HC50 > 10,000 MUg mL(-1)) and exhibit excellent mammalian cell biocompatibility. Structure function analysis indicated that the antimicrobial activity and mammalian cell biocompatibility of the star nanoparticles could be optimized by modifying the molar ratio of polylysine to glycopolymers arms. The technology described herein thus represents an innovative approach that could be used to fight deadly infectious diseases. PMID- 26859231 TI - Transcatheter aortic valve-in-valve implantation and sutureless aortic valve replacement: two strategies for one goal in redo patients. AB - BACKGROUND: The most appropriate approach for high-risk patients with degenerated bioprostheses remains a matter of debate. The aim of the study was to evaluate the clinical and hemodynamic outcome of redo patients undergoing transcatheter aortic valve-in-valve implantation (VinV-TAVI) and sutureless aortic valve replacement (AVR), with assessment of patient-prosthesis mismatch (PPM) in the perioperative and follow-up period. METHODS: From 2010, 343 patients underwent TAVI and 220 patients underwent sutureless AVR at our institution. Among these, 14 patients had prior bioprosthetic AVR and indication for reintervention because of valve degeneration. Patients from the TAVI group (N.=6) underwent VinV-TAVI, and patients from the sutureless group (N.=8) underwent redo AVR. RESULTS: Mean age was 78.8+/-3 years in the sutureless group and 80.2+/-2.3 in the VinV-TAVI group. Logistic EuroSCORE was 36.4+/-24.1% and 33.8+/-13.8% in the sutureless and VinV-TAVI group, respectively. There was no in-hospital death. No patient was lost to follow-up (21+/-13 months, range 6 to 42). Quality of life measured with the EQ-5D questionnaire improved by 65% in the sutureless group and by 67% in the VinV-TAVI group. At follow-up echocardiographic evaluation, no paravalvular leak or intraprosthetic regurgitation was observed in either group. The mean iEOA was 0.96+/-0.08 vs. 0.71+/-0.15 cm2/m2 in the sutureless vs. VinV-TAVI group. CONCLUSIONS: In patients undergoing redo aortic valve surgery for degenerated bioprostheses, both VinV-TAVI and sutureless AVR are effective in terms of clinical outcome. As regards echocardiographic evaluation, no leak was observed in either group and no cases of severe PPM were recorded in the sutureless group. PMID- 26859232 TI - Promising strategies to minimize reperfusion injury in STEMI. AB - Morbidity in patients presenting with acute ST-segment elevation myocardial infarction remains significant despite prompt reperfusion by primary percutaneous coronary intervention. This has been partly attributed to "myocardial reperfusion injury" whereby the process of restoring coronary blood flow paradoxically induces myocardial injury and cardiomyocyte death, mitigating the full beneficial effects of reperfusion. A large number of cardioprotective therapies to reduce myocardial infarct size have been investigated in preclinical and small proof-of concept clinical studies with mixed results. In this article, we provide an overview of the most promising cardioprotective therapies for reducing myocardial infarct size that warrant further investigation in outcome studies. PMID- 26859233 TI - Accelerating Steered Molecular Dynamics: Toward Smaller Velocities in Forced Unfolding Simulations. AB - The simulation of forced unfolding experiments, in which proteins are pulled apart, is conventionally done using steered molecular dynamics. We present here a hybrid scheme in which accelerated molecular dynamics is used together with steered molecular dynamics. We show that the new scheme changes the force distance curves mainly in the region around the force maximum and thus demonstrate that the improved equilibration of the protein-solvent system brought about by using accelerated molecular dynamics makes the simulation more comparable to experimental data. PMID- 26859234 TI - Molecules at the Quantum-Classical Nanoparticle Interface: Giant Mn70 Single Molecule Magnets of ~4 nm Diameter. AB - Two Mn70 torus-like molecules have been obtained from the alcoholysis in EtOH and 2-ClC2H4OH of [Mn12O12(O2CMe)16(H2O)4].4H2O.2MeCO2H (1) in the presence of NBu(n)4MnO4 and an excess of MeCO2H. The reaction in EtOH afforded [Mn70O60(O2CMe)70(OEt)20(EtOH)16(H2O)22] (2), whereas the reaction in ClC2H4OH gave [Mn70O60(O2CMe)70(OC2H4Cl)20(ClC2H4OH)18(H2O)22] (3). The complexes are nearly isostructural, each possessing a Mn70 torus structure consisting of alternating near-linear [Mn3(MU3-O)4] and cubic [Mn4(MU3-O)2(MU3-OR)2] (R = OEt, 2; R = OC2H4Cl, 3) subunits, linked together via syn,syn-MU-bridging MeCO2(-) and MU3-bridging O(2-) groups. 2 and 3 have an overall diameter of ~4 nm and crystallize as highly ordered supramolecular nanotubes. Alternating current (ac) magnetic susceptibility measurements, performed on microcrystalline samples in the 1.8-10 K range and a 3.5 G ac field with oscillation frequencies in the 5 1500 Hz range, revealed frequency-dependent out-of-phase signals below ~2.4 K for both molecules indicative of the slow magnetization relaxation of single-molecule magnets (SMMs). Single-crystal, magnetization vs field studies on both complexes revealed hysteresis loops below 1.5 K, thus confirming 2 and 3 to be new SMMs. The hysteresis loops do not show the steps that are characteristic of quantum tunneling of magnetization (QTM). However, low-temperature studies revealed temperature-independent relaxation rates below ~0.2 K for both compounds, the signature of ground state QTM. Fitting of relaxation data to the Arrhenius equation gave effective barriers for magnetization reversal (Ueff) of 23 and 18 K for 2 and 3, respectively. Because the Mn70 molecule is close to the classical limit, it was also studied using a method based on the Neel-Brown model of thermally activated magnetization reversal in a classical single-domain magnetic nanoparticle. The field and sweep-rate dependence of the coercive field was investigated and yielded the energy barrier, the spin, the Arrhenius pre exponential, and the cross-over temperature from the classical to the quantum regime. The validity of this approach emphasizes that large SMMs can be considered as being at or near the quantum-classical nanoparticle interface. PMID- 26859235 TI - Synthesis and Characterization of the Novel Nitric Oxide (NO) Donating Compound, S-nitroso-N-acetyl-D-penicillamine Derivatized Cyclam (SNAP-Cyclam). AB - Nitric oxide (NO) has been heavily studied over the past two decades due to its multitude of physiological functions and its potential therapeutic promise. Of major interest is the desire to fabricate or coat implanted devices with an NO releasing material that will impart the appropriate dose and duration of NO release to positively mediate the biological response to the medical device, thereby improving its safety and efficacy. To date, this goal has not yet been achieved, despite very promising early research. Herein, we describe the synthesis and NO release properties of a novel NO donor which covalently links the S-nitrosothiol, S-nitroso-N-acetyl-D-penicillamine (SNAP), to the macrocycle, cyclam (SNAP-cyclam). This compound can then be blended into a wide variety of polymer matrices, imparting NO release to the polymer system. This release can be initiated and controlled by transition metal catalysis, thermal degradation or photolytic release of NO from the composite NO-releasing material. SNAP-cyclam is capable of releasing physiologically relevant levels of NO for up to 3 months in vitro when blended into poly(l-lactic acid) thin films. PMID- 26859236 TI - Electroconvulsive therapy (ECT) and aerobic exercise training (AET) increased plasma BDNF and ameliorated depressive symptoms in patients suffering from major depressive disorder. AB - BACKGROUND: To treat patients suffering from major depressive disorder (MDD), research has focused on electroconvulsive therapy (ECT) and aerobic exercise training (AET). Brain derived neurotrophic factor (BDNF) seems to be key in MDD. The aims of the present study were therefore two-fold, to investigate in a three arm interventional study the differential effects of ECT, ECT plus AET, and AET alone in patients suffering from TR-MDD on 1. depressive symptoms and 2. plasma BDNF (pBDNF). METHODS: 60 patients with MDD (mean age: 31 years; 31.6% female patients) were randomly assigned either to the ECT, ECT + AET, or AET condition. The AET condition consisted of treadmill exercise for 45 min, three times a week. Both depression severity and pBDNF levels were assessed at baseline and 4 weeks later. All patients were further treated with an SSRI standard medication. RESULTS: pBDNF levels increased over time in all three study conditions, though, highest increase was observed in the ECT + EAT condition, and lowest increase was observed in the AET condition. Depressive symptoms decreased in all three conditions over time, though, strongest decrease was observed in the ECT + AET condition. The combination of ECT + AET led to significantly greater remission rates than in either the ECT or AET alone conditions. BDNF levels were not associated with symptoms of depression. CONCLUSIONS: The pattern of results suggests that ECT, AET and particularly their combination are promising directions for the treatment of patients suffering from MDD, and that it remains unclear to what extent pBDNF is key and a reliable biomarker for MDD. PMID- 26859237 TI - Implementing efficient and sustainable collaboration between National Immunization Technical Advisory Groups: Report on the 3rd International Technical Meeting, Paris, France, 8-9 December 2014. AB - Many experts on vaccination are convinced that efforts should be made to encourage increased collaboration between National Immunization Technical Advisory Groups on immunization (NITAGs) worldwide. International meetings were held in Berlin, Germany, in 2010 and 2011, to discuss improvement of the methodologies for the development of evidence-based vaccination recommendations, recognizing the need for collaboration and/or sharing of resources in this effort. A third meeting was held in Paris, France, in December 2014, to consider the design of specific practical activities and an organizational structure to enable effective and sustained collaboration. The following conclusions were reached: (i) The proposed collaboration needs a core functional structure and the establishment or strengthening of an international network of NITAGs. (ii) Priority subjects for collaborative work are background information for recommendations, systematic reviews, mathematical models, health economic evaluations and establishment of common frameworks and methodologies for reviewing and grading the evidence. (iii) The programme of collaborative work should begin with participation of a limited number of NITAGs which already have a high level of expertise. The amount of joint work could be increased progressively through practical activities and pragmatic examples. Due to similar priorities and already existing structures, this should be organized at regional or subregional level. For example, in the European Union a project is funded by the European Centre for Disease Prevention and Control (ECDC) with the aim to set up a network for improving data, methodology and resource sharing and thereby supporting NITAGs. Such regional networking activities should be carried out in collaboration with the World Health Organization (WHO). (iv) A global steering committee should be set up to promote international exchange between regional networks and to increase the involvement of less experienced NITAGs. NITAGs already collaborate at the global level via the NITAG Resource Centre, a web based platform developed by the Health Policy and Institutional Development Unit (WHO Collaborating Centre) of the Agence de Medecine Preventive (AMP-HPID). It would be appropriate to continue facilitating the coordination of this global network through the AMP-HPID NITAG Resource Centre. (v) While sharing work products and experiences, each NITAG would retain responsibility for its own decision-making and country-specific recommendations. PMID- 26859238 TI - One year duration of immunity of the modified live bovine viral diarrhea virus type 1 and type 2 and bovine herpesvirus-1 fractions of Vista(r) Once SQ vaccine. AB - Three studies were performed to determine the duration of immunity of the bovine viral diarrhea virus type 1 and type 2 (BVDV-1 and BVDV-2) and bovine herpesvirus 1 (BHV-1) fractions of a commercially prepared modified-live vaccine. Vista(r) Once SQ (Vista(r)) vaccine contains five modified-live viruses, BVDV-1, BVDV-2, BHV-1, bovine respiratory syncytial virus, and bovine parainfluenza 3 virus, and two modified-live bacteria, Pasteurella multocida and Mannheimia haemolytica. For all three studies, calves were administered a single dose of vaccine or placebo vaccine subcutaneously, and were challenged with one of the three virulent viruses at least one year following vaccination. Calves were evaluated daily following challenge for clinical signs of disease associated with viral infection, nasal swab samples were evaluated for virus shedding, and serum was tested for neutralizing antibodies. Following the BVDV-1 and BVDV-2 challenges, whole blood was evaluated for white blood cell counts, and for the BVDV-2 study, whole blood was also evaluated for platelet counts. Calves vaccinated with BVDV type 1a, were protected from challenge with BVDV type 1b, and had significant reductions in clinical disease, fever, leukopenia, and virus shedding compared to control calves. Vaccinated calves in the BVDV-2 study were protected from clinical disease, mortality, fever, leukopenia, thrombocytopenia, and virus shedding compared to controls. Vaccinated calves in the BHV-1 study were protected from clinical disease and fever, and had significantly reduced duration of nasal virus shedding. These three studies demonstrated that a single administration of the Vista(r) vaccine to healthy calves induces protective immunity against BVDV-1, BVDV-2 and BHV-1 that lasts at least one year following vaccination. PMID- 26859240 TI - A qualitative study of healthcare provider awareness and informational needs regarding the nine-valent HPV vaccine. AB - The 9-valent Human Papillomavirus (HPV) vaccine, 9vHPV, was licensed in the U.S. in December, 2014. We assessed healthcare provider (HCP) awareness of the newly approved vaccine and identified questions HCPs have about the vaccine. As part of a larger study, we used semi-structured interviews to ask 22 pediatric HCPs about their awareness of 9vHPV, questions they have about the vaccine, and questions they anticipate from patients and parents. Interviews were audio-recorded and transcribed then analyzed using inductive content analysis. Over half were aware of the vaccine but few HCPs claimed to be familiar with it. HCPs indicated several questions with common themes pertaining to efficacy, side effects, and cost. Only half of HCPs believed patients or parents would have questions. The results suggest strategies and areas for health systems and public health organizations to target in order to resolve unmet educational needs among HCPs regarding 9vHPV. PMID- 26859241 TI - Study of the Interactions of Fusarium virguliforme Toxin FvTox1 with Synthetic Peptides by Molecular Simulations and a Label-Free Biosensor. AB - Fusarium virguliforme is a soil borne pathogen that causes sudden death syndrome (SDS) in soybean plants. This pathogenic disease may result in severe soybean yield suppression and can cause serious economic harm. It has been shown that the FvTox1 toxin produced by the pathogen may be the root cause of foliar SDS. Anti FvTox1 single-chain variable fragment antibody expressed in transgenic soybean plants was shown to neutralize the FvTox1 toxin involved in foliar SDS development. Here, we have investigated the binding affinities of FvTox1 with four FvTox1-interacting peptides of 7 to 12 amino acids identified from phage display libraries using both bioinformatics-based molecular simulations and label free bioassays with a unique photonic crystal biosensor. Results from the molecular simulations have predicted the interaction energies and 3-dimensional (3D) structures of FvTox1 and FvTox1-interacting peptide complexes. Our label free binding assays have further provided the interaction strength of FvTox1 with four different FvTox1-interacting peptides and experimentally confirmed the simulation results obtained from bioinformatics-based molecular calculations. PMID- 26859239 TI - Active opioid use does not attenuate the humoral responses to inactivated influenza vaccine. AB - BACKGROUND: Influenza vaccination is recommended for vulnerable individuals, including active drug users, to prevent influenza complications and decrease influenza spread. Recent studies suggest that opioids negatively regulate immune responses in experimental models, but the extent to which opioid use will affect the humoral responses to influenza vaccine in humans is unknown. This information is critical in maximizing vaccination efforts. OBJECTIVE: To determine whether there is a difference in antibody response after influenza vaccination in heroin or methadone users compared to control subjects. METHODS: We studied active heroin users, subjects on methadone maintenance treatment (MMT) and subjects that did not use any drugs before and 1 and 4 weeks after vaccination with trivalent influenza vaccine (TIV). We measured hemagglutination inhibition and microneutralization titers, and we compared geometric mean titers (GMT), and rates of seroprotection and seroconversion for each of the vaccine strains among the 3 groups of subjects. RESULTS: Heroin users, subjects on MMT and non-user controls mount a similarly robust serologic response to TIV. GMT and rates of seroprotection and seroconversion were not significantly different among groups. CONCLUSION: Our results suggest that opioid use do not significantly alter antibody responses to influenza vaccine supporting the vaccination effort in these populations. PMID- 26859242 TI - General false positive ELISA reactions in visceral leishmaniasis. Implications for the use of enzyme immunoassay analyses in tropical Africa. AB - Leishmaniasis is a neglected disease in tropical countries. Clinical and laboratory features may mimic autoimmune diseases and this can complicate the Leishmania diagnosis. Due to our previous investigation for false anti-CCP2 reactivity in Leishmania-infected subjects and our interest in immunity against the joint-specific collagen type II (CII) in rheumatoid arthritis (RA) we investigated the same cohort for anti-CII antibodies. We found elevated anti-CII reactivity in Leishmania-infected patients as compared to controls. When anti-CII OD values were compared with BSA-blocked control plates we found higher reactivity against BSA than in CII-coated plates in many Leishmania-infected patients. The percentage of such false positive anti-CII reactions increased with inflammatory activity, and was found in almost all Leishmania patients with highly active inflammatory disease, but was as low in Sudanese healthy controls as well as among Swedish RA patients. The correlation coefficients between false positive anti-CII and anti-CCP2 measured with a commercial ELISA were highest for patients with the most inflammatory disease but non-significant for Sudanese controls and Swedish RA patients, arguing that our findings may have general implications for ELISA measurements in leishmaniasis. ELISA investigations in areas endemic for leishmaniasis might benefit from individual-specific control wells for each serum sample. This approach might also be applicable to other geographical areas or patient groups with high incidence of inflammatory and infectious diseases. PMID- 26859244 TI - Pivotal Role and Regulation of Proton Transfer in Water Oxidation on Hematite Photoanodes. AB - Hematite is a promising material for solar water splitting; however, high efficiency remains elusive because of the kinetic limitations of interfacial charge transfer. Here, we demonstrate the pivotal role of proton transfer in water oxidation on hematite photoanodes using photoelectrochemical (PEC) characterization, the H/D kinetic isotope effect (KIE), and electrochemical impedance spectroscopy (EIS). We observed a concerted proton-electron transfer (CPET) characteristic for the rate-determining interfacial hole transfer, where electron transfer (ET) from molecular water to a surface-trapped hole was accompanied by proton transfer (PT) to a solvent water molecule, demonstrating a substantial KIE (~3.5). The temperature dependency of KIE revealed a highly flexible proton transfer channel along the hydrogen bond at the hematite/electrolyte interface. A mechanistic transition in the rate-determining step from CPET to ET occurred after OH(-) became the dominant hole acceptor. We further modified the proton-electron transfer sequence with appropriate proton acceptors (buffer bases) and achieved a greater than 4-fold increase in the PEC water oxidation efficiency on a hematite photoanode. PMID- 26859243 TI - Temporal biological variability in dendritic cells and regulatory T cells in peripheral blood of healthy adults. AB - BACKGROUND: Studies evaluating circulating dendritic cells (DCs) and natural and induced regulatory T cells (nTregs, iTregs) are often obtained at a single time point and difficult to interpret without understanding their intrinsic day-to-day biologic variability. METHODS: We investigated the day-to-day variability in quantifying DCs, nTregs (FoxP3(+)CD25(+)CD4(+)) and cytokine production by iTregs (granzyme B-GZB, Th1/2 cytokines following CD3 plus CD46 in vitro activation) from peripheral blood mononuclear cells (PBMCs) collected on three consecutive days in healthy adults. Intraclass correlation coefficients (ICCs) were used to evaluate intra-individual variability. RESULTS: In 10 healthy adults, the %PBMCs of plasmacytoid (pDC) and myeloid (mDC1 and mDC2) were 0.27 +/- 0.12, 0.22 +/- 0.10, and 0.02 +/- 0.02, with ICC 0.91, 0.90, and 0.17 respectively. Natural Tregs (3.27 +/- 1.27% CD4(+) cells) had an ICC of 0.86. Inducible Tregs (GZB positive, 35.3 +/- 17.7% CD4(+) cells) had an ICC of 0.77. The ICCs for IL-10, TNF-alpha, IFN-gamma, IL-4, and IL-5 production by iTregs were 0.49, 0.63, 0.68, 0.74, and 0.82, respectively. There were no significant changes in ICC (<0.1) after adjusting for age, gender and atopy except for IL-4. Substantial variability for iTregs was determined for the control condition (PBS with IL-2). CONCLUSIONS: No meaningful day-to-day biologic variability was observed for the quantification of nTregs, pDC and mDC1 in normal adults; however, there was substantial variability in measuring mDC2 proportions and iTreg production of IL 10. These results suggest obtaining an average of several measurements over time to determine the most representative value of these biologic measures. PMID- 26859245 TI - Recruitment and retention of physicians in rural Alberta: the spousal perspective. AB - INTRODUCTION: The overall geographic distribution of physicians in Canada, including Alberta, is misaligned with the population distribution. Some strategies, such as debt repayment, are currently in practice to increase recruitment and retention of physicians in rural locations. Of the factors influencing choice of practice location, 'spousal influence' is considered to play a significant role in recruitment and retention of physicians in literature. Most studies have focused on the physicians' perspective of their spouses' influence on staying in a rural location. This study is unique as it approaches rural recruitment and retention from the perspective of the physician spouse. METHODS: The physician population for this study consisted of doctors practicing in rural southern Alberta. Participants were recruited via an email invitation and were invited to complete an online survey. The survey collected information regarding physician demographics and some relationship characteristics. The email invitation also contained a link to a second survey specific to the physician spouse or partner, asking a similar panel of questions. Physicians were asked to request their spouse or partner to complete this survey. Semi-structured interviews were conducted for those who consented to be contacted for interviews. RESULTS: Descriptive statistical analysis of the survey data was carried out. Thematic analysis of the qualitative interview data was conducted and was organized into three sections. The first and second sections present the personal experiences of rural recruitment and rural retention. The third section presents recommendations made by physicians and spouses to improve these processes. Specific interview quotes led the authors to derive themes under each section. CONCLUSIONS: The results of this study raise the voice and profile of the spouse in the process of rural recruitment and retention. In this study, the spouses of Canadian medical graduates were a positive influence in rural recruitment and retention, while the spouses of international medical graduates were generally less supportive of a rural lifestyle. Considerations to accommodate the educational, professional and cultural needs of the physician spouse must be incorporated into policy if large areas of underserved rural communities will continue to rely on international recruitment. PMID- 26859246 TI - Risk factors associated with growth failure in the follow-up of very low birth weight newborns. AB - OBJECTIVE: To determine risk factors during neonatal hospital stay and follow-up associated with failure to thrive in the first year of life of very low birth weight newborns. METHODS: Study of preterm very low birth weight newborns followed from 2006 to 2013 in a public institutional hospital program. The study included newborns that attended at least one appointment in each of the three periods: Period I, up to 3 months of corrected age (CA); Period II, 4-6 months of CA; and Period III, 7-12 months of CA. The variables were analyzed by logistic regression with XLSTAT 2014 software (Microsoft(r), WA, USA). Failure to thrive (Z-score below -2 SD) was classified as a dichotomous dependent variable (0 - failure/1 - success), while the other variables were classified as explanatory variables for the hospitalization periods and for each of the follow-up periods (I, II, and III). RESULTS: Children born adequate for gestational age increased the chance of Z-score for weight at discharge>-2 SD (OR=10.217; 95% CI: 1.117 93.436). Metabolic bone disease and retinopathy of prematurity in Period I, as well as hospital readmissions in Periods II and III during follow-up increased the chance of Z-score<-2 SD. CONCLUSION: Failure to thrive is influenced by intrauterine factors and, subsequently, by several morbidities, both in the birth and hospitalization period, as well as in the post-discharge period and thus, such variables should be prioritized in the follow-up. PMID- 26859247 TI - Nutritional screening in hospitalized pediatric patients: a systematic review. AB - OBJECTIVE: This systematic review aimed to verify the available scientific evidence on the clinical performance and diagnostic accuracy of nutritional screening tools in hospitalized pediatric patients. DATA SOURCE: A search was performed in the Medline (National Library of Medicine United States), LILACS (Latin American and Caribbean Health Sciences), PubMed (US National Library of Medicine National Institutes of Health), in the SCIELO (Scientific Electronic Library Online), through CAPES portal (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior), bases Scopus e Web of Science. The descriptors used in accordance with the Descriptors in Health Sciences (DeCS)/Medical Subject Headings (MeSH) list were "malnutrition", "screening", and "pediatrics", as well as the equivalent words in Portuguese. SUMMARY OF THE FINDINGS: The authors identified 270 articles published between 2004 and 2014. After applying the selection criteria, 35 were analyzed in full and eight articles were included in the systematic review. We evaluated the methodological quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). Five nutritional screening tools in pediatrics were identified. Among these, the Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) showed high sensitivity, almost perfect inter-rater agreement and between the screening and the reference standard; the Screening Tool Risk on Nutritional Status and Growth (STRONGkids) showed high sensitivity, lower percentage of specificity, substantial intra-rater agreement, and ease of use in clinical practice. CONCLUSIONS: The studies included in this systematic review showed good performance of the nutritional screening tools in pediatrics, especially STRONGkids and STAMP. The authors emphasize the need to perform for more studies in this area. Only one tool was translated and adapted to the Brazilian pediatric population, and it is essential to carry out studies of tool adaptation and validation for this population. PMID- 26859248 TI - Influence of passive smoking on learning in elementary school. AB - OBJECTIVE: To analyze the association between household smoking and the development of learning in elementary schoolchildren. METHODS: Cross-sectional study with 785 students from the 2nd to the 5th year of elementary school. Students were evaluated by the School Literacy Screening Protocol to identify the presence of learning disabilities. Mothers/guardians were interviewed at home through a validated questionnaire. Descriptive and bivariate analysis, as well as multivariate Poisson regression, were performed. RESULTS: In the final model, the variables associated with learning difficulties were current smoking at the household in the presence of the child (PR=6.10, 95% CI: 4.56 to 8.16), maternal passive smoking during pregnancy (PR=1.46, 95% CI: 1.07 to 2.01), students attending the 2nd and 3rd years of Elementary School (PR=1.44, 95% CI: 1.10 to 1.90), and being children of mothers with only elementary level education (PR=1.36, 95% CI: 1.04 to 1.79). CONCLUSION: The study demonstrated an association between passive exposure to tobacco smoke and learning difficulties at school. PMID- 26859250 TI - What Is Moving in Hybrid Halide Perovskite Solar Cells? AB - Organic-inorganic semiconductors, which adopt the perovskite crystal structure, have perturbed the landscape of contemporary photovoltaics research. High efficiency solar cells can be produced with solution-processed active layers. The materials are earth abundant, and the simple processing required suggests that high-throughput and low-cost manufacture at scale should be possible. While these materials bear considerable similarity to traditional inorganic semiconductors, there are notable differences in their optoelectronic behavior. A key distinction of these materials is that they are physically soft, leading to considerable thermally activated motion. In this Account, we discuss the internal motion of methylammonium lead iodide (CH3NH3PbI3) and formamidinium lead iodide ([CH(NH2)2]PbI3), covering: (i) molecular rotation-libration in the cuboctahedral cavity; (ii) drift and diffusion of large electron and hole polarons; (iii) transport of charged ionic defects. These processes give rise to a range of properties that are unconventional for photovoltaic materials, including frequency-dependent permittivity, low electron-hole recombination rates, and current-voltage hysteresis. Multiscale simulations, drawing from electronic structure, ab initio molecular dynamic and Monte Carlo computational techniques, have been combined with neutron diffraction measurements, quasi-elastic neutron scattering, and ultrafast vibrational spectroscopy to qualify the nature and time scales of the motions. Electron and hole motion occurs on a femtosecond time scale. Molecular libration is a sub-picosecond process. Molecular rotations occur with a time constant of several picoseconds depending on the cation. Recent experimental evidence and theoretical models for simultaneous electron and ion transport in these materials has been presented, suggesting they are mixed-mode conductors with similarities to fast-ion conducting metal oxide perovskites developed for battery and fuel cell applications. We expound on the implications of these effects for the photovoltaic action. The temporal behavior displayed by hybrid perovskites introduces a sensitivity in materials characterization to the time and length scale of the measurement, as well as the history of each sample. It also poses significant challenges for accurate materials modeling and device simulations. There are large differences between the average and local crystal structures, and the nature of charge transport is too complex to be described by common one-dimensional drift-diffusion models. Herein, we critically discuss the atomistic origin of the dynamic processes and the associated chemical disorder intrinsic to crystalline hybrid perovskite semiconductors. PMID- 26859251 TI - Iron/ABNO-Catalyzed Aerobic Oxidation of Alcohols to Aldehydes and Ketones under Ambient Atmosphere. AB - We report a new Fe(NO3)3.9H2O/9-azabicyclo[3.3.1]nonan-N-oxyl catalyst system that enables efficient aerobic oxidation of a broad range of primary and secondary alcohols to the corresponding aldehydes and ketones at room temperature with ambient air as the oxidant. The catalyst system exhibits excellent activity and selectivity for primary aliphatic alcohol oxidation. This procedure can also be scaled up. Kinetic analysis demonstrates that C-H bond cleavage is the rate determining step and that cationic species are involved in the reaction. PMID- 26859252 TI - Experimental and Theoretical Study of the OH-Initiated Photo-oxidation of Formamide. AB - The kinetics of OH radical reaction with formamide was studied by the relative rate method employing proton transfer reaction-mass spectrometry detection at the European Photochemical Reactor in Valencia, Spain. The rate coefficient was determined to be (4.5 +/- 0.4) * 10(-12) cm(3) molecule(-1) s(-1) at 309 +/- 3 K and 1013 +/- 1 hPa. Isocyanic acid was observed as the sole product. The experimental results are supported by quantum chemical calculations and kinetic simulations using a master equation model. The calculated rate coefficient is independent of pressure at tropospheric conditions and can be accurately described by an Arrhenius expression having negative activation energy. The reaction is predicted to proceed exclusively via C-H abstraction. PMID- 26859249 TI - Topologically Diverse Human Membrane Proteins Partition to Liquid-Disordered Domains in Phase-Separated Lipid Vesicles. AB - The integration of membrane proteins into "lipid raft" membrane domains influences many biochemical processes. The intrinsic structural properties of membrane proteins are thought to mediate their partitioning between membrane domains. However, whether membrane topology influences the targeting of proteins to rafts remains unclear. To address this question, we examined the domain preference of three putative raft-associated membrane proteins with widely different topologies: human caveolin-3, C99 (the 99 residue C-terminal domain of the amyloid precursor protein), and peripheral myelin protein 22. We find that each of these proteins are excluded from the ordered domains of giant unilamellar vesicles containing coexisting liquid-ordered and liquid-disordered phases. Thus, the intrinsic structural properties of these three topologically distinct disease linked proteins are insufficient to confer affinity for synthetic raft-like domains. PMID- 26859253 TI - Psychological Health and Lifestyle Management Preconception and in Pregnancy. AB - Healthful lifestyles before and during pregnancy are important to facilitate healthy outcomes for mother and baby. For example, behaviors such as a sedentary lifestyle and consuming an energy-dense/nutrient-poor diet increase the risk of overweight/obesity before pregnancy and excessive weight gain during pregnancy, leading to adverse maternal and child health outcomes. Maternal psychopathology may be implicated in the development of suboptimal maternal lifestyle behaviors before and during pregnancy, perhaps through impacts on motivation. This article explores this notion using maternal obesity and excessive gestational weight gain as examples of the health impacts of psychological states. We suggest that factors such as psychological well-being, individual motivation for behavior change, and broader environmental influences that affect both individual and system-wide determinants all play important roles in promoting healthy lifestyles periconception and are key modifiable aspects for intervention designers to consider when trying to improve dietary behaviors and increase physical activity before and during pregnancy. In addition, implementing system-wide changes that impact positively on individual and environmental barriers to behavior change that are sustainable, measureable, and effective is required. PMID- 26859255 TI - Quantitative Analysis of Prostate Multiparametric MR Images for Detection of Aggressive Prostate Cancer in the Peripheral Zone: A Multiple Imager Study. AB - Purpose To assess the intermanufacturer variability of quantitative models in discriminating cancers with a Gleason score of at least 7 among peripheral zone (PZ) lesions seen at 3-T multiparametric magnetic resonance (MR) imaging. Materials and Methods An institutional review board-approved prospective database of 257 patients who gave written consent and underwent T2-weighted, diffusion weighted, and dynamic contrast material-enhanced imaging before prostatectomy was retrospectively reviewed. It contained outlined lesions found to be suspicious for malignancy by two independent radiologists and classified as malignant or benign after correlation with prostatectomy whole-mount specimens. One hundred six patients who underwent imaging with 3-T MR systems from two manufacturers were selected (data set A, n = 72; data set B, n = 34). Eleven parameters were calculated in PZ lesions: normalized T2-weighted signal intensity, skewness and kurtosis of T2-weighted signal intensity, T2 value, wash-in rate, washout rate, time to peak (TTP), mean apparent diffusion coefficient (ADC), 10th percentile of the ADC, and skewness and kurtosis of the histogram of the ADC values. Parameters were selected on the basis of their specificity for a sensitivity of 0.95 in diagnosing cancers with a Gleason score of at least 7, and the area under the receiver operating characteristic curve (AUC) for the models was calculated. Results The model of the 10th percentile of the ADC with TTP yielded the highest AUC in both data sets. In data set A, the AUC was 0.90 (95% confidence interval [CI]: 0.85, 0.95) or 0.89 (95% CI: 0.82, 0.94) when it was trained in data set A or B, respectively. In data set B, the AUC was 0.84 (95% CI: 0.74, 0.94) or 0.86 (95% CI: 0.76, 0.95) when it was trained in data set A or B, respectively. No third variable added significantly independent information in any data set. Conclusion The model of the 10th percentile of the ADC with TTP yielded accurate results in discriminating cancers with a Gleason score of at least 7 among PZ lesions at 3 T in data from two manufacturers. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26859256 TI - Characterization of Axonal Disease in Patients with Multiple Sclerosis Using High Gradient-Diffusion MR Imaging. AB - Purpose To evaluate the ability of high-gradient-diffusion magnetic resonance (MR) imaging by using gradient strengths of up to 300 mT/m to depict axonal disease in lesions and normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) and to compare high-gradient-diffusion MR findings in these patients with those in healthy control subjects. Materials and Methods In this HIPAA-compliant institutional review board-approved prospective study in which all subjects provided written informed consent, six patients with relapsing remitting MS and six healthy control subjects underwent diffusion-weighted imaging with a range of diffusion weightings performed with a 3-T human MR imager by using gradient strengths of up to 300 mT/m. A model of intra-axonal, extra axonal, and free water diffusion was fitted to obtain estimates of axon diameter and density. Differences in axon diameter and density between lesions and NAWM in patients with MS were assessed by using the nonparametric Wilcoxon matched-pairs signed rank test, and differences between NAWM in subjects with MS and white matter in healthy control subjects were assessed by using the Mann-Whitney U test. Results MS lesions showed increased mean axon diameter (10.3 vs 7.9 MUm in the genu, 10.4 vs 9.3 MUm in the body, and 10.6 vs 8.2 MUm in the splenium; P < .05) and decreased axon density ([0.48 vs 1.1] * 10(10)/m(2) in the genu, [0.40 vs 0.70] * 10(10)/m(2) in the body, and [0.35 vs 1.1] * 10(10)/m(2) in the splenium; P < .05) compared with adjacent NAWM. No significant difference in mean axon diameter or axon density was detected between NAWM in subjects with MS and white matter in healthy control subjects. Conclusion High-gradient-diffusion MR imaging using gradient strengths of up to 300 mT/m can be used to characterize axonal disease in patients with MS, with results that agree with known trends from neuropathologic data showing increased axon diameter and decreased axon density in MS lesions when compared with NAWM. ((c)) RSNA, 2016 Online supplemental material is available for this article. PMID- 26859257 TI - Analysis of HIV-1c-Specific CTL Responses with HIV-1 Reservoir Size and Forms. AB - Cytotoxic T lymphocytes (CTL) are critical in cellular immune responses; therefore the study of CTL responses is profound in HIV-1 eradication. We aim to dissect the relationship between HIV-1 reservoir size and the magnitude and recognition of viral-specific CTL responses. An IFN-gamma ELISpot assay with peptides spanning the HIV-1 clade C consensus sequences were designed to analyze HIV-1c-specific CTL responses. HIV-1 DNA, integrated HIV-1 DNA, and 2-LTR HIV-1 DNA were quantitated by real-time PCR. We observed significant increases in total HIV-1 DNA and integrated HIV-1 DNA after highly active antiretroviral treatment (HAART) compared with naive patients. Total HIV-1 DNA had a significant negative correlation with HIV-1c-specific CTL response magnitude. Baseline CD4(+) T lymphocyte counts and antiretroviral treatment affected the size of the HIV-1 reservoirs. Taken together, HIV-1-specific CTL responses correlated with the size of HIV-1 reservoir. In addition, HIV-1-specific CTL response against p17 was associated with low integral efficiency of HIV-1, which might be a biomarker to evaluate the efficacy of HAART. PMID- 26859258 TI - To Pay or Not to Pay? Is that the Question? PMID- 26859259 TI - Structural Insights into the Fluoroquinolone Resistance Mechanism of Shigella flexneri DNA Gyrase and Topoisomerase IV. AB - Traveler's diarrhea (TD) is an important public health concern that can result from a variety of intestinal pathogens, including bacteria, parasites, and virus. A number of antibiotics are being used to cure TD, but due to widespread use of these antibiotics, the pathogens are becoming resistant to them. In this work, we performed docking studies of DNA gyraseA (GyrA) and topoisomerase IV (ParC) of Shigella flexneri and their mutants with two different fluoroquinolones, ciprofloxacin and norfloxacin, to understand their resistance mechanism at the structural level. S. flexneri strains with mutations at serine 83 to leucine and aspartic acid 87 to glutamate or asparagine of GyrA and that of serine 80 to isoleucine in ParC have decreased susceptibility to fluoroquinolones. This analysis revealed that interaction of ciprofloxacin/norfloxacin with all the mutants was weaker than the interaction of ciprofloxacin/norfloxacin with the wild type. This study highlights the importance of aspartic acid and serine in GyrA and that of serine in ParC, forming bonds with ciprofloxacin/norfloxacin, which may play a crucial role in antibiotic resistance. This work corelates very well with the experimental outcomes and gives a good explanation for fluoroquinolone resistance in S. flexneri. PMID- 26859260 TI - Millimeter-scale epileptiform spike propagation patterns and their relationship to seizures. AB - OBJECTIVE: Current mapping of epileptic networks in patients prior to epilepsy surgery utilizes electrode arrays with sparse spatial sampling (~1.0 cm inter electrode spacing). Recent research demonstrates that sub-millimeter, cortical column-scale domains have a role in seizure generation that may be clinically significant. We use high-resolution, active, flexible surface electrode arrays with 500 MUm inter-electrode spacing to explore epileptiform local field potential (LFP) spike propagation patterns in two dimensions recorded from subdural micro-electrocorticographic signals in vivo in cat. In this study, we aimed to develop methods to quantitatively characterize the spatiotemporal dynamics of epileptiform activity at high-resolution. APPROACH: We topically administered a GABA-antagonist, picrotoxin, to induce acute neocortical epileptiform activity leading up to discrete electrographic seizures. We extracted features from LFP spikes to characterize spatiotemporal patterns in these events. We then tested the hypothesis that two-dimensional spike patterns during seizures were different from those between seizures. MAIN RESULTS: We showed that spatially correlated events can be used to distinguish ictal versus interictal spikes. SIGNIFICANCE: We conclude that sub-millimeter-scale spatiotemporal spike patterns reveal network dynamics that are invisible to standard clinical recordings and contain information related to seizure-state. PMID- 26859262 TI - Exercise: Is More Always Better? AB - Do greater levels of exercise always promote relatively higher levels of daily energy expenditure and health? Recent studies challenge the traditional assumption that 'more exercise is better' by suggesting daily energy expenditure and health plateaus are reached beyond which incremental gains are minimal. PMID- 26859261 TI - Divergent evolution of vitamin B9 binding underlies Juno-mediated adhesion of mammalian gametes. AB - The interaction between egg and sperm is the first necessary step of fertilization in all sexually reproducing organisms. A decade-long search for a protein pair mediating this event in mammals culminated in the identification of the glycosylphosphatidylinositol (GPI)-anchored glycoprotein Juno as the egg plasma membrane receptor of sperm Izumo1 [1,2]. The Juno-Izumo1 interaction was shown to be essential for fertilization since mice lacking either gene exhibit sex-specific sterility, making these proteins promising non-hormonal contraceptive targets [1,3]. No structural information is available on how gamete membranes interact at fertilization, and it is unclear how Juno - which was previously named folate receptor (FR) 4, based on sequence similarity considerations - triggers membrane adhesion by binding Izumo1. Here, we report the crystal structure of Juno and find that the overall fold is similar to that of FRalpha and FRbeta but with significant flexibility within the area that corresponds to the rigid ligand-binding site of these bona fide folate receptors. This explains both the inability of Juno to bind vitamin B9/folic acid [1], and why mutations within the flexible region can either abolish or change the species specificity of this interaction. Furthermore, structural similarity between Juno and the cholesterol-binding Niemann-Pick disease type C1 protein (NPC1) suggests how the modified binding surface of Juno may recognize the helical structure of the amino-terminal domain of Izumo1. As Juno appears to be a mammalian innovation, our study indicates that a key evolutionary event in mammalian reproduction originated from the neofunctionalization of the vitamin B9-binding pocket of an ancestral folate receptor molecule. PMID- 26859263 TI - Supergenes: The Genomic Architecture of a Bird with Four Sexes. AB - Supergenes are clusters of physically linked, co-evolving genes that often control complex traits. A new study clarifies the origin and possible fate of a fascinating supergene that determines the coloration and mating behavior of a widespread North American bird. PMID- 26859264 TI - Plant Physiology: Redefining the Enigma of Metabolism in Stomatal Movement. AB - Stomata open at the leaf epidermis, driven by solute accumulation in the surrounding guard cells. Transmembrane ion transport has long been recognised to contribute to this process. A new study makes it clear that guard cells also metabolise starch to accelerate opening. PMID- 26859265 TI - Neural Plasticity: Dopamine Tunes the Mushroom Body Output Network. AB - Two recent studies in Drosophila provide evidence that dopamine can drive synaptic depression and facilitation, supporting models in which learning and the behavioral state of the fly guide behavior by tuning mushroom body output synapses. PMID- 26859266 TI - Bacterial Speciation: Genetic Sweeps in Bacterial Species. AB - One theory of bacterial speciation states that bacterial and animal species share the property of cohesion, meaning that diversity within a species is constrained. A new study provides direct evidence that genome-wide sweeps can limit diversity within bacterial species. PMID- 26859267 TI - Plant Reproduction: Self-Incompatibility to Go. AB - In a new study, the Papaver rhoeas (poppy family) self-incompatibility system has been transferred into Arabidopsis thaliana, a distantly related plant with a very different floral structure. The simple poppy self-incompatibility system may finally make it possible to introduce this potentially valuable trait into any plant. PMID- 26859268 TI - Intestinal Stem Cells: Got Calcium? AB - Calcium ions are well-known intracellular signalling molecules. A new study identifies local cytoplasmic calcium as a central integrator of metabolic and proliferative signals in Drosophila intestinal stem cells. PMID- 26859269 TI - Posttranslational Regulation: A Way to Evolve. AB - A new study shows that differences in the regulation of lipin can account for the different strategies of nuclear division in two closely related fission yeast species. PMID- 26859270 TI - Plant Breeding: Surprisingly, Less Sex Is Better. AB - Introduction of apomixis, asexual reproduction through seeds, into crop species has the potential to dramatically transform plant breeding. A new study demonstrates that traits can be stably transferred between generations in newly produced apomictic lines, and heralds a breeding revolution needed to increase food production for the growing planet. PMID- 26859272 TI - Rewilding is the new Pandora's box in conservation. AB - Rewilding--the proposed restoration of ecosystems through the (re-)introduction of species--is seen by many as a way to stem the loss of biodiversity and the functions and services that biodiversity provides to humanity. In addition, rewilding might lead to increased public engagement and enthusiasm for biodiversity. But what exactly is rewilding, and is it based on sound ecological understanding? Here, we show that there is a worrying lack of consensus about what rewilding is and what it isn't, which jeopardizes a clearer account of rewilding's aims, benefits and potential consequences. We also point out that scientific support for the main ecological assumptions behind rewilding, such as top-down control of ecosystems, is limited. Moreover, ecological systems are dynamic and ever-evolving, which makes it challenging to predict the consequences of introducing novel species. We also present examples of introductions or re introductions that have failed, provoking unexpected negative consequences, and highlight that the control and extirpation of individuals of failed translocations has been shown to be extremely challenging and economically costly. Some of rewilding's loudest proponents might argue that we are advocating doing nothing instead, but we are not; we are only advocating caution and an increased understanding and awareness of what is unknown about rewilding, and what its potential outputs, especially ecological consequences, might be. PMID- 26859273 TI - Tickling. AB - A quick guide to tickling, a form of laughter-evoking play that can be considered as an index of agency, with a discussion of its taxonomic distribution and its possible relationship to traditional measures of self-recognition. PMID- 26859274 TI - The nitrogen cycle. AB - Nitrogen is the fourth most abundant element in cellular biomass, and it comprises the majority of Earth's atmosphere. The interchange between inert dinitrogen gas (N2) in the extant atmosphere and 'reactive nitrogen' (those nitrogen compounds that support, or are products of, cellular metabolism and growth) is entirely controlled by microbial activities. This was not the case, however, in the primordial atmosphere, when abiotic reactions likely played a significant role in the inter-transformation of nitrogen oxides. Although such abiotic reactions are still important, the extant nitrogen cycle is driven by reductive fixation of dinitrogen and an enzyme inventory that facilitates dinitrogen-producing reactions. Prior to the advent of the Haber-Bosch process (the industrial fixation of N2 into ammonia, NH3) in 1909, nearly all of the reactive nitrogen in the biosphere was generated and recycled by microorganisms. Although the Haber-Bosch process more than quadrupled the productivity of agricultural crops, chemical fertilizers and other anthropogenic sources of fixed nitrogen now far exceed natural contributions, leading to unprecedented environmental degradation. PMID- 26859271 TI - Fertilization Mechanisms in Flowering Plants. AB - Compared with the animal kingdom, fertilization is particularly complex in flowering plants (angiosperms). Sperm cells of angiosperms have lost their motility and require transportation as a passive cargo by the pollen tube cell to the egg apparatus (egg cell and accessory synergid cells). Sperm cell release from the pollen tube occurs after intensive communication between the pollen tube cell and the receptive synergid, culminating in the lysis of both interaction partners. Following release of the two sperm cells, they interact and fuse with two dimorphic female gametes (the egg and the central cell) forming the major seed components embryo and endosperm, respectively. This process is known as double fertilization. Here, we review the current understanding of the processes of sperm cell reception, gamete interaction, their pre-fertilization activation and fusion, as well as the mechanisms plants use to prevent the fusion of egg cells with multiple sperm cells. The role of Ca(2+) is highlighted in these various processes and comparisons are drawn between fertilization mechanisms in flowering plants and other eukaryotes, including mammals. PMID- 26859275 TI - Morbid attraction to leopard urine in Toxoplasma-infected chimpanzees. AB - Parasites are sometimes capable of inducing phenotypic changes in their hosts to improve transmission [1]. Toxoplasma gondii, a protozoan that infects a broad range of warm-blooded species, is one example that supports the so-called 'parasite manipulation hypothesis': it induces modifications in rodents' olfactory preferences, converting an innate aversion for cat odor into attraction and probably favoring trophic transmission to feline species, its only definitive hosts [2]. In humans, T. gondii induces behavioral modifications such as personality changes, prolonged reaction times and decreased long-term concentration [3]. However, modern humans are not suitable intermediate hosts because they are no longer preyed upon by felines. Consequently, behavioral modifications in infected people are generally assumed to be side effects of toxoplasmosis or residual manipulation traits that evolved in appropriate intermediate hosts. An alternative hypothesis, however, states that these changes result from parasite manipulative abilities that evolved when human ancestors were still under significant feline predation [3,4]. As such, T. gondii also alters olfactory preferences in humans; infected men rate cat urine, but not tiger urine, as pleasant while non-infected men do not [5]. To unravel the origin of Toxoplasma-induced modifications in humans, we performed olfactory tests on a living primate still predated by a feline species. We found in our closest relative, the chimpanzee (Pan troglodytes troglodytes), that Toxoplasma-infected (TI) animals lost their innate aversion towards the urine of leopards (Panthera pardus), their only natural predator. By contrast, we observed no clear difference in the response of TI and Toxoplasma-non-infected (TN) animals towards urine collected from other definitive feline hosts that chimpanzees do not encounter in nature. Although the adaptive value of parasitically induced behavior should be assessed carefully, we suggest that the behavioral modification we report could increase the probability of chimpanzee predation by leopards for the parasite's own benefit. This possible parasite adaptation would hence suggest that Toxoplasma-induced modifications in modern humans are an ancestral legacy of our evolutionary past. PMID- 26859276 TI - Acute Pancreatitis Associated With Antipsychotic Medication: Evaluation of Clinical Features, Treatment, and Polypharmacy in a Series of Cases. AB - BACKGROUND: Antipsychotic-associated acute pancreatitis presents like pancreatitis from other causes, requiring clinical judgment, tests, and decision support to establish the diagnosis. Many new cases of atypical antipsychotic pancreatitis have been established, and current decision supports are out of date as antipsychotic polypharmacy is being recognized. Given the population frequency of psychosis and frequency of antipsychotic prescribing, we reviewed published cases summarizing common clinical findings and antipsychotics associated with acute pancreatitis to updating earlier decision support. METHODS: Case reports of antipsychotic pancreatitis from 1990 to 2015 were reviewed and abstracted by independent reviewers. Demographic, clinical features, management, and Naranjo and probability scores were abstracted and reviewed for associations. Appropriate statistical tests were selected for normally and non-normally distributed data. RESULTS: We summarized 41 cases of acute pancreatitis associated with antipsychotics, and cases were younger men (59%) (mean age, 39 years). Alcohol, diabetes, and previous lithiasis appeared in 27%; polypharmacy was associated with 53% of cases, and 80% had concomitant use of other medication linked to pancreatitis.The median lipase, amylase, and alkaline phosphate during acute presentation were 1210 IU/L (range, 243-5482 IU/L), 492 IU/L (range, 3-2916 IU/L), and 152 IU/L (range, 119-367 IU/L), respectively. Median exposure to antipsychotics were 49 days (range, 5-3,650 days); most were mild (63%, n = 26), several severe (27%, n = 11), and few fatal (10%, n = 4). DISCUSSION: We identified 41 reports of antipsychotic-related acute pancreatitis, many associated with antipsychotic polypharmacy. Olanzapine, risperidone, quetiapine, aripiprazole, and ziprasidone are associated with acute pancreatitis and often in combination with mood stabilizers. PMID- 26859277 TI - Successful Use of Single Doses of Granulocyte-Colony Stimulating Factor (G-CSF) in the Treatment of Late-Onset Agranulocytosis Associated With Clozapine in a Patient With Treatment-Resistant Schizophrenia: A Case Report. PMID- 26859278 TI - Somnambulism During Monotherapy With Mixed Amphetamine Salts. PMID- 26859279 TI - Transition to a Moist Greenhouse with CO2 and solar forcing. AB - Water-rich planets such as Earth are expected to become eventually uninhabitable, because liquid water turns unstable at the surface as temperatures increase with solar luminosity. Whether a large increase of atmospheric concentrations of greenhouse gases such as CO2 could also destroy the habitability of water-rich planets has remained unclear. Here we show with three-dimensional aqua-planet simulations that CO2-induced forcing as readily destabilizes the climate as does solar forcing. The climate instability is caused by a positive cloud feedback and leads to a new steady state with global-mean sea-surface temperatures above 330 K. The upper atmosphere is considerably moister in this warm state than in the reference climate, implying that the planet would be subject to substantial loss of water to space. For some elevated CO2 or solar forcings, we find both cold and warm equilibrium states, implying that the climate transition cannot be reversed by removing the additional forcing. PMID- 26859280 TI - Promoting Testicular Cancer Awareness and Screening: A Systematic Review of Interventions. AB - BACKGROUND: Testicular cancer (TC) is a relatively curable malignancy that predominantly affects young males. Key decision makers discourage TC screening because of lack of evidence about the benefits of this practice, whereas others argue that men must be aware of normal versus abnormal testicular findings. Despite the debate on TC surveillance, a number of research efforts are still being made to increase men's awareness of TC and its screening. OBJECTIVE: The aim of this study was to systematically review studies that were conducted to enhance men's knowledge and awareness regarding TC and its screening and increase their TC screening intentions and practices. METHODS: Studies published in English between 2004 and 2014 were reviewed using 3 e-databases, and interventions that were in line with the review aims were selected. RESULTS: A total of 3076 records were screened for eligibility, and 11 studies met the inclusion criteria. The majority of the reviewed interventions successfully enhanced men's awareness of TC and its screening and increased their intentions to perform testicular self-examination. Examples include videos about TC, shower gel sachets, stickers, and posters, a television show, a university campaign, and high self-efficacy messages about TC screening. Men at risk of health disparities were underrepresented in the reviewed literature. CONCLUSIONS: A number of interesting channels through which men can learn about TC were identified. Examples include social media and mass media. IMPLICATIONS FOR PRACTICE: Given the controversy that surrounds TC screening, nurses can play a key role in increasing men's awareness of TC rather than advising periodical TC self examination. PMID- 26859281 TI - Using Religious Songs as an Integrative and Complementary Therapy for the Management of Psychological Symptoms Among African American Cancer Survivors. AB - BACKGROUND: Acupuncture, acupressure, yoga, meditation, cognitive-behavioral techniques, and, to a lesser extent, music are among those integrative and complementary therapies with known beneficial effects on psychological symptoms. However, noticeably absent from this research is the use of religious song as a type of integrative and complementary therapy. OBJECTIVE: The aim of this study was to explore how religious songs were used to alleviate psychological symptoms associated with a cancer diagnosis among a sample of older African American cancer survivors. DESIGN AND METHODS: Thirty-one older African American cancer survivors residing in the Southeastern US participated in a qualitative descriptive study involving criterion sampling, open-ended semistructured interviews, and qualitative content analysis. RESULTS: Participants used religious songs in response to feeling depressed, low, or sad; feeling weak and seeking strength to endure treatment; and feeling worried, anxious, or fearful. Religious songs were also a source of support and hope. Types of religious songs included instructive, thanksgiving and praise, memory of forefathers, communication with God, and life after death. CONCLUSION: Religious songs appear to be an important form of religious expression in this population and used to manage psychological symptoms. IMPLICATIONS FOR PRACTICE: Integrative and complementary oncology therapy has generally focused on yoga, meditation, acupuncture, and cognitive-behavioral techniques. However, religious songs are an important strategy used among older African American cancer patients. Religious songs can be readily integrated into cancer care. The incorporation of religious songs into spiritually based support groups and other integrative and complementary therapies might enhance health outcomes among this medically underserved cancer population. PMID- 26859282 TI - Qualitative Study of Cervical Cancer Screening Among Lesbian and Bisexual Women and Transgender Men. AB - BACKGROUND: Lesbian, bisexual, and queer (LBQ) women, as well as transgender men, are less likely than their heterosexual and female-identifying counterparts to access cervical cancer screening services. Although numerous factors that influence receipt of cervical screening have been identified, several gaps in research and knowledge merit additional research. OBJECTIVE: The aims of this study were to examine cervical cancer screening behaviors of LBQ women and transgender men using American Cancer Society guidelines as the standards for comparison and to determine factors that influence participation in cervical cancer screening. METHODS: A convenience sample of 21- to 65-year-old LBQ women and transgender men was recruited from the Internet and community events. Qualitative data were collected through in-depth telephone interviews and open ended questions on an online questionnaire. A deductive-inductive content analysis approach was used. RESULTS: The sample was mostly non-Hispanic white women who identified as lesbian. Most were routine cervical cancer screeners. Eighteen factors/themes were identified in the data and were contextualized within a health services theoretical framework. CONCLUSIONS: This study showed that although some factors overlap with the general female population, there are other areas that are specific to LBQ women and transgender men. Creating welcoming and inclusive healthcare environments is particularly important to facilitating cervical screening among LBQ women. IMPLICATIONS FOR PRACTICE: Nurse leaders can modify clinical environments, and clinical nurses can be educated to provide safe care for LBQ women and transgender men. PMID- 26859283 TI - Protecting: A Grounded Theory Study of Younger Children's Experiences of Coping With Maternal Cancer. AB - BACKGROUND: A diagnosis of parental cancer affects all members of the family unit, especially young school-age children. Few studies, however, have explored children's experiences at the time when their parents are actually receiving treatment. Understanding the children's experiences will provide additional insight into children's coping abilities. OBJECTIVE: The purpose of this study is to develop a grounded theory of children's day-to-day experiences as they live with their mother who has been recently diagnosed with, and is receiving treatment for, early-stage breast cancer. METHODS: Using classic grounded theory methodology, data were collected through 28 interviews with 7- to 11-year-old children whose mothers had been diagnosed with early-stage breast cancer during the previous 4 months. RESULTS: Protecting was the main concern of the children during their mothers' diagnosis and treatment phase. The children addressed this concern through 3 cyclical and iterative processes of shifting normality, shielding and transitioning. CONCLUSIONS: The findings provide a mechanism for understanding how the perceived loss of the "well" mother raised concerns for the children and resulted in adaptations of roles and responsibilities and a period of biographical disruption. This understanding could serve as a catalyst for how we relate with children and engage with parents to enhance children's coping strategies during a maternal cancer diagnosis. IMPLICATIONS FOR PRACTICE: New insights provided by this theory can guide clinical practice and generate hypotheses to test interventions to support children and their parents to cope during the time of maternal cancer diagnosis. PMID- 26859284 TI - Anesthetic Implications for Tracheal Injury During Bronchoscopy-Guided Percutaneous Dilational Tracheostomy. AB - Bronchoscopic-guided percutaneous dilational tracheostomy has become one of the most common elective tracheostomy methods for patients requiring prolonged ventilatory support. The safety profile, patient selection, and risks as well as complication management, when compared with an open surgical technique, remain somewhat controversial with no clear recommendations. We present a case of a critically ill patient undergoing percutaneous dilation tracheostomy complicated by tracheal wall injury and airway loss. The airway was successfully conservatively managed as well as the tracheal injury. Anesthetic implications, safety, and management options as well as recommendations are reviewed. PMID- 26859285 TI - False positive dengue NS1 antigen test in a traveller with an acute Zika virus infection imported into Switzerland. AB - We report the first case of an acute Zika virus infection imported into Switzerland by a traveller returning from Canoa Quebrada, Ceara state, in the north-eastern part of Brazil. Due to a false positive dengue virus NS1 antigen test, IgG antibody seroconversion and a suggestive clinical picture,an acute dengue fever was initially considered. However, because of lack of specific IgM antibodies, stationary IgG antibody titre and a negative dengue virus PCR test result, a dengue virus infection was excluded and a cross-reaction with other, causative flaviviruses was postulated. Based on recent reports of Zika fever cases in the north-eastern parts of Brazil, an acute Zika virus infection was suspected. Because of a lack of commercially available Zika virus diagnostic tests, the case was confirmed in the WHO reference laboratory. As the clinical presentation of Zika virus infection can be confused with dengue fever and chikungunya fever, and because of possible public health implications, all patients returning from affected areas should be additionally tested for Zika virus. This case illustrates the urgent medical need for a broadly available assay capable of differentiating Zika from Dengue infections. PMID- 26859286 TI - The tooth exposome in children's health research. AB - PURPOSE OF REVIEW: The exposome concept proposes a comprehensive assessment of environmental exposures from the prenatal period onwards. However, determining exposure timing, especially over the prenatal period, is a major challenge in environmental epidemiologic studies. RECENT FINDINGS: For decades, teeth have been used to estimate long-term cumulative exposure to metals. Recently developed high-dimensional analytical methods, which combine sophisticated histological and chemical analysis to precisely sample tooth layers that correspond to specific life stages, have the potential to reconstruct the exposome in the second and third trimesters of prenatal development and during early childhood. SUMMARY: A retrospective temporal exposomic approach that precisely measures exposure intensity 'and timing' during prenatal and early childhood development would substantially aid epidemiologic investigations, particularly case-control studies of rare health outcomes. PMID- 26859287 TI - Satellite remote sensing in epidemiological studies. AB - PURPOSE OF REVIEW: Particulate matter air pollution is a ubiquitous exposure linked with multiple adverse health outcomes for children and across the life course. The recent development of satellite-based remote-sensing models for air pollution enables the quantification of these risks and addresses many limitations of previous air pollution research strategies. We review the recent literature on the applications of satellite remote sensing in air quality research, with a focus on their use in epidemiological studies. RECENT FINDINGS: Aerosol optical depth (AOD) is a focus of this review and a significant number of studies show that ground-level particulate matter can be estimated from columnar AOD. Satellite measurements have been found to be an important source of data for particulate matter model-based exposure estimates, and recently have been used in health studies to increase the spatial breadth and temporal resolution of these estimates. SUMMARY: It is suggested that satellite-based models improve our understanding of the spatial characteristics of air quality. Although the adoption of satellite-based measures of air quality in health studies is in its infancy, it is rapidly growing. Nevertheless, further investigation is still needed in order to have a better understanding of the AOD contribution to these prediction models in order to use them with higher accuracy in epidemiological studies. PMID- 26859288 TI - Children's Physical Activity Behavior during School Recess: A Pilot Study Using GPS, Accelerometer, Participant Observation, and Go-Along Interview. AB - Schoolyards are recognized as important settings for physical activity interventions during recess. However, varying results have been reported. This pilot study was conducted to gain in-depth knowledge of children's physical activity behavior during recess using a mixed-methods approach combining quantitative GPS and accelerometer measurements with qualitative go-along group interviews and participant observations. Data were collected during three weekdays in a public school in Denmark. Eighty-one children (47 girls) wore an accelerometer (ActiGraph GT3X) and GPS (QStarz BT-Q1000xt), sixteen children participated in go-along group interviews, and recess behavior was observed using an ethnographical participant observation approach. All data were analyzed separated systematically answering the Five W Questions. Children were categorized into Low, Middle and High physical activity groups and these groups were predominantly staying in three different locations during recess: school building, schoolyard and field, respectively. Mostly girls were in the building remaining in there because of a perceived lack of attractive outdoor play facilities. The children in the schoolyard were predominantly girls who preferred the schoolyard over the field to avoid the competitive soccer games on the field whereas boys dominated the field playing soccer. Using a mixed-methods approach to investigate children's physical activity behavior during recess helped gain in depth knowledge that can aid development of future interventions in the school environment. PMID- 26859290 TI - Correction: Association between Perfluorinated Compound Exposure and Miscarriage in Danish Pregnant Women. PMID- 26859289 TI - A Point Mutation in p190A RhoGAP Affects Ciliogenesis and Leads to Glomerulocystic Kidney Defects. AB - Rho family GTPases act as molecular switches regulating actin cytoskeleton dynamics. Attenuation of their signaling capacity is provided by GTPase activating proteins (GAPs), including p190A, that promote the intrinsic GTPase activity of Rho proteins. In the current study we have performed a small-scale ENU mutagenesis screen and identified a novel loss of function allele of the p190A gene Arhgap35, which introduces a Leu1396 to Gln substitution in the GAP domain. This results in decreased GAP activity for the prototypical Rho-family members, RhoA and Rac1, likely due to disrupted ordering of the Rho binding surface. Consequently, Arhgap35-deficient animals exhibit hypoplastic and glomerulocystic kidneys. Investigation into the cystic phenotype shows that p190A is required for appropriate primary cilium formation in renal nephrons. P190A specifically localizes to the base of the cilia to permit axoneme elongation, which requires a functional GAP domain. Pharmacological manipulations further reveal that inhibition of either Rho kinase (ROCK) or F-actin polymerization is able to rescue the ciliogenesis defects observed upon loss of p190A activity. We propose a model in which p190A acts as a modulator of Rho GTPases in a localized area around the cilia to permit the dynamic actin rearrangement required for cilia elongation. Together, our results establish an unexpected link between Rho GTPase regulation, ciliogenesis and glomerulocystic kidney disease. PMID- 26859291 TI - Neurogenic Effects of Cell-Free Extracts of Adipose Stem Cells. AB - Stem-cell-based therapies are regarded as promising treatments for neurological disorders, and adipose-derived stem cells (ASCs) are a feasible source of clinical application of stem cell. Recent studies have shown that stem cells have a therapeutic potential for use in the treatment of various illnesses through paracrine action. To examine the effects of cell components of ASCs on neural stem cells (NSCs), we treated cell-free extracts of ASCs (CFE-ASCs) containing various components with brain-derived NSCs. To elucidate the effects of CFE-ASCs in NSC proliferation, we treated mouse subventricular zone-derived cultured NSCs with various doses of CFE-ASCs. As a result, CFE-ASCs were found to induce the proliferation of NSCs under conditions of growth factor deprivation in a dose dependent manner (p<0.01). CFE-ASCs increase the expression of neuron and astrocyte differentiation markers including Tuj-1 (p<0.05) and glial fibrillary acidic protein (p<0.01) without altering the cell's fate in differentiating NSCs. In addition, treatment with CFE-ASCs induces an increase in neurite numbers (p<0.01) and lengths of NSCs (p<0.05). Furthermore, CFE-ASCs rescue the hydrogen peroxide-induced reduction of NSCs' viability (p<0.05) and neurite branching (p<0.01). Findings from our study indicate that CFE-ASCs support the survival, proliferation and differentiation of NSCs accompanied with neurite outgrowth, suggesting that CFE-ASCs can modulate neurogenesis in the central nervous system. PMID- 26859292 TI - Factors Associated with Knowledge of and Willingness for Adult Male Circumcision in Changsha, China. AB - BACKGROUND: Male circumcision (MC) has been shown to reduce the risk of male genital diseases. MC is not commonly practiced among Chinese males and little is known about the factors associated with their knowledge of and willingness for MC. This study was to explore the knowledge regarding the foreskin among Chinese males and to identify factors associated with their willingness to undergo circumcision. METHODS: A total of 237 patients with redundant prepuce/phimosis were interviewed through face-to-face interviews. The items on the questionnaire included: demographics, an objective scale assessing knowledge about the foreskin, willingness to have MC, the attitudes of sexual partners and doctors toward redundant prepuce/phimosis, and the approaches that patients used to acquire knowledge regarding the prepuce. Univariate analysis and multiple logistic regression analysis were performed to identify factors that are associated with willingness to be circumcised (WTC). RESULTS: A total of 212 patients completed the interview. Multivariable logistic regression showed that three factors were significantly associated with WTC: being married (OR = 0.43), perceiving redundant prepuce/phimosis as a disease (OR = 1.93), and if a patient's partner supported MC (OR = 1.39). 58% (n = 122) had received information about the foreskin from another party: 18% (n = 37) from school, 8% (n = 17) from family, 17% (n = 36) from friends, 27% (n = 57) from health care providers. About 4% (n = 8) believed that their partners disliked their redundant prepuce/phimosis. 20% (n = 42) had received doctors' advice to undergo circumcision. CONCLUSION: Knowledge about the foreskin was low among Chinese males. Our study elucidates the factors associated with WTC and suggests that more education of the population about the foreskin can help improve the recognition of a correctible abnormality and help patients assess the potential role of MC in their health. PMID- 26859293 TI - Galectin-1-Induced Autophagy Facilitates Cisplatin Resistance of Hepatocellular Carcinoma. AB - Hepatocellular carcinoma (HCC) is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin 1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin 1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients. PMID- 26859294 TI - Inhibition of Plasminogen Activator Inhibitor-1 Attenuates Transforming Growth Factor-beta-Dependent Epithelial Mesenchymal Transition and Differentiation of Fibroblasts to Myofibroblasts. AB - Transforming growth factor-beta (TGF-beta) is central during the pathogenesis of pulmonary fibrosis, in which the plasminogen activator inhibitor-1 (PAI-1) also has an established role. TGF-beta is also known to be the strongest inducer of PAI-1. To investigate the link between PAI-1 and TGF-beta in fibrotic processes, we evaluated the effect of SK-216, a PAI-1-specific inhibitor, in TGF-beta dependent epithelial-mesenchymal transition (EMT) and fibroblast to myofibroblast differentiation. In human alveolar epithelial A549 cells, treatment with TGF-beta induced EMT, whereas co-treatment with SK-216 attenuated the occurrence of EMT. The inhibition of TGF-beta-induced EMT by SK-216 was also confirmed in the experiment using murine epithelial LA-4 cells. Blocking EMT by SK-216 inhibited TGF-beta-induced endogenous production of PAI-1 and TGF-beta in A549 cells as well. These effects of SK-216 were not likely mediated by suppressing either Smad or ERK pathways. Using human lung fibroblast MRC-5 cells, we demonstrated that SK 216 inhibited TGF-beta-dependent differentiation of fibroblasts to myofibroblasts. We also observed this inhibition by SK-216 in human primary lung fibroblasts. Following these in vitro results, we tested oral administration of SK-216 into mice injected intratracheally with bleomycin. We found that SK-216 reduced the degree of bleomycin-induced pulmonary fibrosis in mice. Although the precise mechanisms underlying the link between TGF-beta and PAI-1 regarding fibrotic process were not determined, PAI-1 seems to act as a potent downstream effector on the pro-fibrotic property of TGF-beta. In addition, inhibition of PAI 1 activity by a PAI-1 inhibitor exerts an antifibrotic effect even in vivo. These data suggest that targeting PAI-1 as a downstream effector of TGF-beta could be a promising therapeutic strategy for pulmonary fibrosis. PMID- 26859295 TI - ePIANNO: ePIgenomics ANNOtation tool. AB - Recently, with the development of next generation sequencing (NGS), the combination of chromatin immunoprecipitation (ChIP) and NGS, namely ChIP-seq, has become a powerful technique to capture potential genomic binding sites of regulatory factors, histone modifications and chromatin accessible regions. For most researchers, additional information including genomic variations on the TF binding site, allele frequency of variation between different populations, variation associated disease, and other neighbour TF binding sites are essential to generate a proper hypothesis or a meaningful conclusion. Many ChIP-seq datasets had been deposited on the public domain to help researchers make new discoveries. However, researches are often intimidated by the complexity of data structure and largeness of data volume. Such information would be more useful if they could be combined or downloaded with ChIP-seq data. To meet such demands, we built a webtool: ePIgenomic ANNOtation tool (ePIANNO, http://epianno.stat.sinica.edu.tw/index.html). ePIANNO is a web server that combines SNP information of populations (1000 Genomes Project) and gene-disease association information of GWAS (NHGRI) with ChIP-seq (hmChIP, ENCODE, and ROADMAP epigenomics) data. ePIANNO has a user-friendly website interface allowing researchers to explore, navigate, and extract data quickly. We use two examples to demonstrate how users could use functions of ePIANNO webserver to explore useful information about TF related genomic variants. Users could use our query functions to search target regions, transcription factors, or annotations. ePIANNO may help users to generate hypothesis or explore potential biological functions for their studies. PMID- 26859296 TI - Strategies for Rapid Muscle Fatigue Reduction during FES Exercise in Individuals with Spinal Cord Injury: A Systematic Review. AB - BACKGROUND: Rapid muscle fatigue during functional electrical stimulation (FES) evoked muscle contractions in individuals with spinal cord injury (SCI) is a significant limitation to attaining health benefits of FES-exercise. Delaying the onset of muscle fatigue is often cited as an important goal linked to FES clinical efficacy. Although the basic concept of fatigue-resistance has a long history, recent advances in biomedical engineering, physiotherapy and clinical exercise science have achieved improved clinical benefits, especially for reducing muscle fatigue during FES-exercise. This review evaluated the methodological quality of strategies underlying muscle fatigue-resistance that have been used to optimize FES therapeutic approaches. The review also sought to synthesize the effectiveness of these strategies for persons with SCI in order to establish their functional impacts and clinical relevance. METHODS: Published scientific literature pertaining to the reduction of FES-induced muscle fatigue was identified through searches of the following databases: Science Direct, Medline, IEEE Xplore, SpringerLink, PubMed and Nature, from the earliest returned record until June 2015. Titles and abstracts were screened to obtain 35 studies that met the inclusion criteria for this systematic review. RESULTS: Following the evaluation of methodological quality (mean (SD), 50 (6) %) of the reviewed studies using the Downs and Black scale, the largest treatment effects reported to reduce muscle fatigue mainly investigated isometric contractions of limited functional and clinical relevance (n = 28). Some investigations (n = 13) lacked randomisation, while others were characterised by small sample sizes with low statistical power. Nevertheless, the clinical significance of emerging trends to improve fatigue-resistance during FES included (i) optimizing electrode positioning, (ii) fine-tuning of stimulation patterns and other FES parameters, (iii) adjustments to the mode and frequency of exercise training, and (iv) biofeedback-assisted FES-exercise to promote selective recruitment of fatigue resistant motor units. CONCLUSION: Although the need for further in-depth clinical trials (especially RCTs) was clearly warranted to establish external validity of outcomes, current evidence was sufficient to support the validity of certain techniques for rapid fatigue-reduction in order to promote FES therapy as an integral part of SCI rehabilitation. It is anticipated that this information will be valuable to clinicians and other allied health professionals administering FES as a treatment option in rehabilitation and aid the development of effective rehabilitation interventions. PMID- 26859297 TI - Urinary Colorimetric Sensor Array and Algorithm to Distinguish Kawasaki Disease from Other Febrile Illnesses. AB - OBJECTIVES: Kawasaki disease (KD) is an acute pediatric vasculitis of infants and young children with unknown etiology and no specific laboratory-based test to identify. A specific molecular diagnostic test is urgently needed to support the clinical decision of proper medical intervention, preventing subsequent complications of coronary artery aneurysms. We used a simple and low-cost colorimetric sensor array to address the lack of a specific diagnostic test to differentiate KD from febrile control (FC) patients with similar rash/fever illnesses. STUDY DESIGN: Demographic and clinical data were prospectively collected for subjects with KD and FCs under standard protocol. After screening using a genetic algorithm, eleven compounds including metalloporphyrins, pH indicators, redox indicators and solvatochromic dye categories, were selected from our chromatic compound library (n = 190) to construct a colorimetric sensor array for diagnosing KD. Quantitative color difference analysis led to a decision tree-based KD diagnostic algorithm. RESULTS: This KD sensing array allowed the identification of 94% of KD subjects (receiver operating characteristic [ROC] area under the curve [AUC] 0.981) in the training set (33 KD, 33 FC) and 94% of KD subjects (ROC AUC: 0.873) in the testing set (16 KD, 17 FC). Color difference maps reconstructed from the digital images of the sensing compounds demonstrated distinctive patterns differentiating KD from FC patients. CONCLUSIONS: The colorimetric sensor array, composed of common used chemical compounds, is an easily accessible, low-cost method to realize the discrimination of subjects with KD from other febrile illness. PMID- 26859298 TI - One-Year Mortality in Older Patients with Cancer: Development and External Validation of an MNA-Based Prognostic Score. AB - PURPOSE: The MNA (Mini Nutritional Assessment) is known as a prognosis factor in older population. We analyzed the prognostic value for one-year mortality of MNA items in older patients with cancer treated with chemotherapy as the basis of a simplified prognostic score. METHODS: The prospective derivation cohort included 606 patients older than 70 years with an indication of chemotherapy for cancers. The endpoint to predict was one-year mortality. The 18 items of the Full MNA, age, gender, weight loss, cancer origin, TNM, performance status and lymphocyte count were considered to construct the prognostic model. MNA items were analyzed with a backward step-by-step multivariate logistic regression and other items were added in a forward step-by-step regression. External validation was performed on an independent cohort of 229 patients. RESULTS: At one year 266 deaths had occurred. Decreased dietary intake (p = 0.0002), decreased protein rich food intake (p = 0.025), 3 or more prescribed drugs (p = 0.023), calf circumference <31 cm (p = 0.0002), tumor origin (p<0.0001), metastatic status (p = 0.0007) and lymphocyte count <1500/mm3 (0.029) were found to be associated with 1-year mortality in the final model and were used to construct a prognostic score. The area under curve (AUC) of the score was 0.793, which was higher than the Full MNA AUC (0.706). The AUC of the score in validation cohort (229 subjects, 137 deaths) was 0.698. CONCLUSION: Key predictors of one-year mortality included cancer cachexia clinical features, comorbidities, the origin and the advanced status of the tumor. The prognostic value of this model combining a subset of MNA items and cancer related items was better than the full MNA, thus providing a simple score to predict 1-year mortality in older patients with an indication of chemotherapy. PMID- 26859299 TI - Intelligence-Augmented Rat Cyborgs in Maze Solving. AB - Cyborg intelligence is an emerging kind of intelligence paradigm. It aims to deeply integrate machine intelligence with biological intelligence by connecting machines and living beings via neural interfaces, enhancing strength by combining the biological cognition capability with the machine computational capability. Cyborg intelligence is considered to be a new way to augment living beings with machine intelligence. In this paper, we build rat cyborgs to demonstrate how they can expedite the maze escape task with integration of machine intelligence. We compare the performance of maze solving by computer, by individual rats, and by computer-aided rats (i.e. rat cyborgs). They were asked to find their way from a constant entrance to a constant exit in fourteen diverse mazes. Performance of maze solving was measured by steps, coverage rates, and time spent. The experimental results with six rats and their intelligence-augmented rat cyborgs show that rat cyborgs have the best performance in escaping from mazes. These results provide a proof-of-principle demonstration for cyborg intelligence. In addition, our novel cyborg intelligent system (rat cyborg) has great potential in various applications, such as search and rescue in complex terrains. PMID- 26859300 TI - SuperSILAC Quantitative Proteome Profiling of Murine Middle Ear Epithelial Cell Remodeling with NTHi. AB - BACKGROUND: Chronic Otitis Media with effusion (COME) develops after sustained inflammation and is characterized by secretory middle ear epithelial metaplasia and effusion, most frequently mucoid. Non-typeable Haemophilus influenzae (NTHi), the most common acute Otitis Media (OM) pathogen, is postulated to promote middle ear epithelial remodeling in the progression of OM from acute to chronic. The goals of this study were to examine histopathological and quantitative proteomic epithelial effects of NTHi challenge in a murine middle ear epithelial cell line. METHODS: NTHi lysates were generated and used to stimulate murine epithelial cells (mMEEC) cultured at air-liquid interface over 48 hours- 1 week. Conditional quantitative Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) of cell lysates was performed to interrogate the global protein production in the cells, using the SuperSILAC technique. Histology of the epithelium over time was done to measure bacterial dependent remodeling. RESULTS: Mass spectrometry analysis identified 2,565 proteins across samples, of which 74 exhibited differential enrichment or depletion in cell lysates (+/-2.0 fold-change; p value<0.05). The key molecular functions regulated by NTHi lysates exposure were related to cell proliferation, death, migration, adhesion and inflammation. Finally, chronic exposure induced significant epithelial thickening of cells grown at air liquid interface. CONCLUSIONS: NTHi lysates drive pathways responsible of cell remodeling in murine middle ear epithelium which likely contributes to observed epithelial hyperplasia in vitro. Further elucidation of these mediators will be critical in understanding the progression of OM from acute to chronic at the molecular level. PMID- 26859303 TI - Physiological Role of Gut Microbiota for Maintaining Human Health. AB - BACKGROUND: The human body is colonized by an extremely complex and abundant aggregation of microbes, collectively referred to as the gut microbiota. Recent studies have focused on the link between these microbes and our health. SUMMARY: Diet contributes to shaping the gut microbial structure and influences metabolic functions of the host. Alteration of the microbial structure and function (dysbiosis) is associated with the pathogenesis of various disorders. Fermentation is the process by which anaerobic bacteria (Firmicutes and Bacteroidetes) break down indigestible carbohydrates to short-chain fatty acids (SCFAs; acetate, propionate and butyrate), collaborating with species specialized in oligosaccharide fermentation (e.g. Bifidobacteria). Butyrate and propionate can regulate intestinal physiology and immune function, while acetate acts as a substrate for lipogenesis and gluconeogenesis. The gut microbiota regulates immune homeostasis via the induction of regulatory T cells and Th17 cells. In addition, butyrate has strong anti-inflammatory effects possibly through the inhibition of histone deacetylase activity. Metabolic products generated by the gut microbiota, such as SCFAs, GABA, tryptophan, serotonin and catecholamine, transmit a signal to resident cells in the gut. KEY MESSAGE: Advances made in the DNA sequencing technology and bioinformatics have revolutionized our understanding of the microbes in the gut. PMID- 26859302 TI - Image Quality Analysis of Eyes Undergoing LASER Refractive Surgery. AB - Laser refractive surgery for myopia increases the eye's higher-order wavefront aberrations (HOA's). However, little is known about the impact of such optical degradation on post-operative image quality (IQ) of these eyes. This study determined the relation between HOA's and IQ parameters (peak IQ, dioptric focus that maximized IQ and depth of focus) derived from psychophysical (logMAR acuity) and computational (logVSOTF) through-focus curves in 45 subjects (18 to 31 yrs) before and 1-month after refractive surgery and in 40 age-matched emmetropic controls. Computationally derived peak IQ and its best focus were negatively correlated with the RMS deviation of all HOA's (HORMS) (r>=-0.5; p<0.001 for all). Computational depth of focus was positively correlated with HORMS (r>=0.55; p<0.001 for all) and negatively correlated with peak IQ (r>=-0.8; p<0.001 for all). All IQ parameters related to logMAR acuity were poorly correlated with HORMS (r<=|0.16|; p>0.16 for all). Increase in HOA's after refractive surgery is therefore associated with a decline in peak IQ and a persistence of this sub standard IQ over a larger dioptric range, vis-a-vis, before surgery and in age matched controls. This optical deterioration however does not appear to significantly alter psychophysical IQ, suggesting minimal impact of refractive surgery on the subject's ability to resolve spatial details and their tolerance to blur. PMID- 26859301 TI - Polyunsaturated Fatty Acid (PUFA) Status in Pregnant Women: Associations with Sleep Quality, Inflammation, and Length of Gestation. AB - Mechanistic pathways linking maternal polyunsaturated fatty acid (PUFA) status with gestational length are poorly delineated. This study examined whether inflammation and sleep quality serve as mediators, focusing on the antiinflammatory omega-3 docosahexaenoic acid (DHA; 22:6n3) and proinflammatory omega-6 arachidonic acid (AA; 20:4n6). Pregnant women (n = 135) provided a blood sample and completed the Pittsburgh Sleep Quality Index (PSQI) at 20-27 weeks gestation. Red blood cell (RBC) fatty acid levels were determined by gas chromatography and serum inflammatory markers [interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, IL-1beta, and C-reactive protein] by electrochemiluminescence using high sensitivity kits. Both higher serum IL-8 (95% CI = 0.10,3.84) and poor sleep (95% CI = 0.03,0.28) served as significant mediators linking lower DHA:AA ratios with shorter gestation. Further, a serial mediation model moving from the DHA:AA ratio -> sleep -> IL-8 -> length of gestation was statistically significant (95% CI = 0.02, 0.79). These relationships remained after adjusting for depressive symptoms, age, BMI, income, race, and smoking. No interactions with race were observed in relation to length of gestation as a continuous variable. However, a significant interaction between race and the DHA:AA ratio in predicting preterm birth was observed (p = 0.049); among African Americans only, odds of preterm birth decreased as DHA:AA increased (p = 0.048). These data support a role for both inflammatory pathways and sleep quality in linking less optimal RBC PUFA status with shorter gestation in African American and European American women and suggest that African-Americans have greater risk for preterm birth in the context of a low DHA:AA ratio. PMID- 26859305 TI - Routine Use of Probiotics in Preterm Infants: Longitudinal Impact on the Microbiome and Metabolome. AB - BACKGROUND: Probiotics are live microbial supplements that colonize the gut and potentially exert health benefit to the host. OBJECTIVES: We aimed to determine the impact of a probiotic (Infloran(r): Lactobacillus acidophilus-NCIMB701748 and Bifidobacterium bifidum-ATCC15696) on the bacterial and metabolic function of the preterm gut while in the neonatal intensive care unit (NICU) and following discharge. METHODS: Stool samples (n = 88) were collected before, during, and after probiotic intake from 7 patients, along with time-matched controls from 3 patients. Samples were also collected following discharge home from the NICU. Samples underwent bacterial profiling analysis by 16S rRNA gene sequencing and quantitative PCR (qPCR), as well as metabolomic profiling using liquid chromatography mass spectrometry. RESULTS: Bacterial profiling showed greater Bifidobacterium (15.1%) and Lactobacillus (4.2%) during supplementation compared to the control group (4.0% and 0%, respectively). While Lactobacillus became reduced after the probiotic had been stopped, Bifidobacterium remained high following discharge, suggestive of successful colonisation. qPCR analysis showed a significant increase (p <= 0.01) in B. bifidum in infants who received probiotic treatment compared to controls, but no significant increase was observed for L. acidophilus (p = 0.153). Metabolite profiling showed clustering based on receiving probiotic or matched controls, with distinct metabolites associated with probiotic administration. CONCLUSIONS: Probiotic species successfully colonise the preterm gut, reducing the relative abundance of potentially pathogenic bacteria, and effecting gut functioning. Bifidobacterium (but not Lactobacillus) colonised the gut in the long term, suggesting the possibility that therapeutically administered probiotics may continue to exert important functional effects on gut microbial communities in early infancy. PMID- 26859304 TI - Quantification of Calcium Amount in a New Experimental Model: A Comparison between Ultrasound and Computed Tomography. AB - PURPOSE: Calcification is an important prognostic factor in aortic valve stenosis. However, there is no ultrasound (US) method available to accurately quantify calcification in this setting to date. We aimed to validate a new US method for measuring the amount of calcium in an in vitro model, and compare it to computed tomography (CT), the current imaging gold standard. MATERIALS AND METHODS: An agar phantom (2% agar) was made, containing 9 different amounts of calcium-hydroxyapatite Ca5(PO4)3OH (2 to 50 mg). The phantoms were imaged with micro-CT and US (10 MHz probe). The calcium area (areacalcium) and its maximum pixel value (PVmax) were obtained. These values were summed to calculate CT and US calcium scores (?(areacalcium * PVmax)) and volumes (?areacalcium). Both US- and CT-calcium scores were compared with the calcium amounts, and with each other. RESULTS: Both calcium scores correlated significantly with the calcium amount (R2 = 0.9788, p<0.0001 and R2 = 0.8154, p<0.0001 for CT and US respectively). Furthermore, there was a significant correlation between US and CT for calcium volumes (R2 = 0.7392, p<0.0001) and scores (R2 = 0.7391, p<0.0001). CONCLUSION: We developed a new US method that accurately quantifies the amount of calcium in an in vitro model. Moreover it is strongly correlated with CT. PMID- 26859307 TI - 10 years follow-up after mid-urethral sling implantation: high rate of cure yet a re-occurrence of OAB-symptoms. AB - AIMS: To assess the long-term outcome of mid-urethral slings regarding urinary incontinence (UI) and lower urinary tract symptoms and to identify risk factors for an unsatisfactory outcome. METHODS: Analysis of a prospective institutional database. For the current analysis only women who reached the 10 years follow-up were eligible. Outcome was assessed using a detailed, non-validated questionnaire on continence status and on several aspects of lower urinary tract function. RESULTS: A total of 256 women were operated during 1999-2004, in 139 (54.3%), a 10 years follow-up was available and these patients were included. Mean age at surgery was 63 years. At the 2, 5, and 10 years follow-up, the percentages of women reporting 0-1 pads/day were 96.4%, 97.1% and 88.5%, respectively. More than 95% of the patients reported no stress UI at the 2, 5, and 10 years follow-up. At baseline, urgency was reported by 61.2%, this figure dropped to 17.3% at 2 years and increased thereafter to 32.4% (5 years) and 41.7% (10 years). De novo urgency was present in 3.6% after 2 years, in 10.8% after 5 years, and 14.4% after 10 years. The percentage of patients with a high degree of treatment satisfaction declined from 79.1% at 2 years to 70.5% at 5 years, and 62.6% at 10 years. Risk factors for an unsatisfactory long-term outcome were advanced age, the presence of urgency, nocturia, and decreased bladder capacity at baseline. CONCLUSIONS: This study confirms the excellent long-term efficacy of mid-urethral slings regarding the management of stress UI. A substantial number of women develop OAB symptoms after the procedure that largely contribute to outcome dissatisfaction. Neurourol. Urodynam. 36:614-619, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26859306 TI - Clinical outcomes in outpatient respiratory syncytial virus infection in immunocompromised children. AB - BACKGROUND: Immunocompromised patients are at high risk for morbidity and mortality due to respiratory syncytial virus (RSV) infection. Increasingly, pediatric patients with malignancy or undergoing transplantation are managed primarily as outpatients. Data regarding the clinical presentation and outcomes of RSV in the outpatient pediatric immunocompromised population are limited. METHODS: We performed a retrospective cohort study of children with hematologic malignancy or hematopoietic or solid organ transplant with laboratory-confirmed RSV infection diagnosed as outpatients at an academic medical center between 2008 and 2013. RESULTS: Of 54 patients with RSV detected while outpatients, 15 (28%) were hospitalized, 7 (13%) received ribavirin, and one (2%) received intravenous immunoglobulin. One (2%) patient was critically ill, but there were no deaths due to RSV infection. Fever (P < 0.01) was associated with increased risk of hospitalization. CONCLUSIONS: Most immunocompromised children with RSV detected while outpatients did not require hospitalization or receive antiviral treatment. Potential studies of RSV therapies should consider inclusion of patients in an ambulatory setting. PMID- 26859308 TI - Artifact removal in the context of group ICA: A comparison of single-subject and group approaches. AB - Independent component analysis (ICA) has been widely applied to identify intrinsic brain networks from fMRI data. Group ICA computes group-level components from all data and subsequently estimates individual-level components to recapture intersubject variability. However, the best approach to handle artifacts, which may vary widely among subjects, is not yet clear. In this work, we study and compare two ICA approaches for artifacts removal. One approach, recommended in recent work by the Human Connectome Project, first performs ICA on individual subject data to remove artifacts, and then applies a group ICA on the cleaned data from all subjects. We refer to this approach as Individual ICA based artifacts Removal Plus Group ICA (IRPG). A second proposed approach, called Group Information Guided ICA (GIG-ICA), performs ICA on group data, then removes the group-level artifact components, and finally performs subject-specific ICAs using the group-level non-artifact components as spatial references. We used simulations to evaluate the two approaches with respect to the effects of data quality, data quantity, variable number of sources among subjects, and spatially unique artifacts. Resting-state test-retest datasets were also employed to investigate the reliability of functional networks. Results from simulations demonstrate GIG-ICA has greater performance compared with IRPG, even in the case when single-subject artifacts removal is perfect and when individual subjects have spatially unique artifacts. Experiments using test-retest data suggest that GIG-ICA provides more reliable functional networks. Based on high estimation accuracy, ease of implementation, and high reliability of functional networks, we find GIG-ICA to be a promising approach. PMID- 26859310 TI - Abnormal functional architecture of amygdala-centered networks in adolescent posttraumatic stress disorder. AB - Posttraumatic stress disorder (PTSD) is a prevalent, debilitating, and difficult to treat psychiatric disorder. Very little is known of how PTSD affects neuroplasticity in the developing adolescent brain. Whereas multiple lines of research implicate amygdala-centered network dysfunction in the pathophysiology of adult PTSD, no study has yet examined the functional architecture of amygdala subregional networks in adolescent PTSD. Using intrinsic functional connectivity analysis, we investigated functional connectivity of the basolateral (BLA) and centromedial (CMA) amygdala in 19 sexually abused adolescents with PTSD relative to 23 matched controls. Additionally, we examined whether altered amygdala subregional connectivity coincides with abnormal grey matter volume of the amygdaloid complex. Our analysis revealed abnormal amygdalar connectivity and morphology in adolescent PTSD patients. More specifically, PTSD patients showed diminished right BLA connectivity with a cluster including dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices (p < 0.05, corrected). In contrast, PTSD patients showed increased left CMA connectivity with a cluster including the orbitofrontal and subcallosal cortices (p < 0.05, corrected). Critically, these connectivity changes coincided with diminished grey matter volume within BLA and CMA subnuclei (p < 0.05, corrected), with CMA connectivity shifts additionally relating to more severe symptoms of PTSD. These findings provide unique insights into how perturbations in major amygdalar circuits could hamper fear regulation and drive excessive acquisition and expression of fear in PTSD. As such, they represent an important step toward characterizing the neurocircuitry of adolescent PTSD, thereby informing the development of reliable biomarkers and potential therapeutic targets. PMID- 26859309 TI - Enhanced brain signal variability in children with autism spectrum disorder during early childhood. AB - Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age-related increase of brain signal variability in a specific timescale in TD children, whereas atypical age-related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region-specifically and timescale-specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical-developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales. PMID- 26859311 TI - A novel joint sparse partial correlation method for estimating group functional networks. AB - Advances in graph theory have provided a powerful tool to characterize brain networks. In particular, functional networks at group-level have great appeal to gain further insight into complex brain function, and to assess changes across disease conditions. These group networks, however, often have two main limitations. First, they are popularly estimated by directly averaging individual networks that are compromised by confounding variations. Secondly, functional networks have been estimated mainly through Pearson cross-correlation, without taking into account the influence of other regions. In this study, we propose a sparse group partial correlation method for robust estimation of functional networks based on a joint graphical models approach. To circumvent the issue of choosing the optimal regularization parameters, a stability selection method is employed to extract networks. The proposed method is, therefore, denoted as JGMSS. By applying JGMSS across simulated datasets, the resulting networks show consistently higher accuracy and sensitivity than those estimated using an alternative approach (the elastic-net regularization with stability selection, ENSS). The robustness of the JGMSS is evidenced by the independence of the estimated networks to choices of the initial set of regularization parameters. The performance of JGMSS in estimating group networks is further demonstrated with in vivo fMRI data (ASL and BOLD), which show that JGMSS can more robustly estimate brain hub regions at group-level and can better control intersubject variability than it is achieved using ENSS. PMID- 26859313 TI - Validity of immunohistochemistry method in predicting HER-2 gene status and association of clinicopathological variables with it in invasive breast cancer patients. AB - Human epidermal growth factor receptor-2 is an important and prognostic factors and one of the most targeted proteins in breast cancer's therapy. There is no globally accepted method for determining its status. Here, we aimed to evaluate the immunohistochemistry method validity in predicting HER-2 status by Fluorescence in situ hybridization method and investigate some clinicopathological variables association with HER-2 amplification. A total of 190 HER-2 2+ and 3+ by immunohistochemistry (IHC) invasive breast cancer cases were enrolled in this study. Fluorescence in situ hybridization (FISH) was performed for these cases using FDA criteria and the association between clinicopathological variables and HER-2 status evaluated. Study consisted of 190 invasive breast cancer patients (160 HER-2 2+ and 30 HER-2 3+). HER-2 FISH amplification according to FDA criteria was found 27.5% (44/160 patients) in HER 2 2+ patients and 83.3% (25/30 patients) in HER-2 3+ patients. Tumors with HER-2 amplification were more likely to be ER-negative (51.0% vs 31.2%, p = 0.013) and PR-negative (52.9% vs 27.0%, p < 0.001). This study showed that immunohistochemistry is not a good method for evaluating HER-2 status and decision-making about trastuzumab therapy even with 3+ score patients. However, this result may not be too strong for IHC 3+ cases due to the limited number of these patients in this study. PMID- 26859314 TI - CRM1 and chromosomal passenger complex component survivin are essential to normal mitosis progress and to preserve keratinocytes from mitotic abnormalities. AB - OBJECTIVE: Human epidermis provides the body a barrier against environmental assaults. To assume this function, the epidermis needs the renewal of keratinocytes allowed by constant mitosis, which replace the exfoliating corneocytes. Keratinocyte stem cells (KSCs) located in the basal epidermis are mitotically active, self-renewing and govern the epithelial stratification by producing renewed source of keratinocytes. Protein complex such as the chromosomal passenger complex (CPC) allows the correct development of this process. The CPC is composed of four members: INCENP, survivin, borealin and aurora kinase B, and the disruption of the CPC during cell division induces mitotic spindle defects and improper repartition of chromosomes. The aim of our study was to investigate the implication of CRM1 and survivin in the progress of mitosis in skin keratinocytes. METHODS: Cultured human keratinocytes and skin biopsies were used in this study. KSCs-enriched population of keratinocytes was isolated from total keratinocytes by differential attachment to a type IV collagen matrix. Survivin and CRM1 expression levels were assessed by immunofluorescence and immunoblotting. Specific siRNAs for each CPC member and for CRM1 were used to determine the relationship between these proteins. Survivin specific siRNA was used to induce the apparition of mitotic abnormalities in cultured keratinocytes. RESULTS: We demonstrated the ability of our compound 'IV08.009' to modulate the expression level of survivin and CRM1 in keratinocytes and in skin biopsies. We observed that members of the CPC are interdependent: siRNA-induced inhibition of one component caused a decrease in the expression of all other CPC members. Downregulation of survivin or CRM1 induced mitotic abnormalities in keratinocytes. However, decreased number of mitotic abnormalities was observed in keratinocytes after 'IV08.009' application. CONCLUSION: Basal keratinocytes may divide frequently during skin lifespan, and signs of deterioration could appear such as loss of protein factors required for correct mitosis. Our findings suggest that mitotic abnormalities can be prevented by the modulation of CRM1 and survivin. We demonstrated the ability of compound 'IV08.009' to efficiently protect cultured keratinocytes from mitotic abnormalities. PMID- 26859312 TI - Lifespan anxiety is reflected in human amygdala cortical connectivity. AB - The amygdala plays a pivotal role in processing anxiety and connects to large scale brain networks. However, intrinsic functional connectivity (iFC) between amygdala and these networks has rarely been examined in relation to anxiety, especially across the lifespan. We employed resting-state functional MRI data from 280 healthy adults (18-83.5 yrs) to elucidate the relationship between anxiety and amygdala iFC with common cortical networks including the visual network, somatomotor network, dorsal attention network, ventral attention network, limbic network, frontoparietal network, and default network. Global and network-specific iFC were separately computed as mean iFC of amygdala with the entire cerebral cortex and each cortical network. We detected negative correlation between global positive amygdala iFC and trait anxiety. Network specific associations between amygdala iFC and anxiety were also detectable. Specifically, the higher iFC strength between the left amygdala and the limbic network predicted lower state anxiety. For the trait anxiety, left amygdala anxiety-connectivity correlation was observed in both somatomotor and dorsal attention networks, whereas the right amygdala anxiety-connectivity correlation was primarily distributed in the frontoparietal and ventral attention networks. Ventral attention network exhibited significant anxiety-gender interactions on its iFC with amygdala. Together with findings from additional vertex-wise analysis, these data clearly indicated that both low-level sensory networks and high-level associative networks could contribute to detectable predictions of anxiety behaviors by their iFC profiles with the amygdala. This set of systems neuroscience findings could lead to novel functional network models on neural correlates of human anxiety and provide targets for novel treatment strategies on anxiety disorders. PMID- 26859315 TI - Serum heart type fatty acid binding protein levels are not changed in hyperthyroidism. AB - BACKGROUND: Heart type fatty acid binding protein (H-FABP) is a small protein and released into the circulation when myocardial damage has occurred. Previous studies have demonstrated that H-FABP is closely associated with cardiac and some endocrinologic disorders including prediabetes, metabolic syndrome, and acromegaly. Hyperthyroism is a well-known disorder associated with cardiovascular diseases. We aimed to investigate the effect of hyperthyrodism on H-FABP levels. METHODS: Forty six patients with hyperthyroidism with no known history of coronary artery disease and 40 healthy controls are involved in the study. Serum H-FABP levels are measured using sandwich enzyme-linked immunosorbent assay. RESULTS: There was no significant difference between serum H-FABP levels of patients with hyperthyroidism and controls (871+/-66 pg/mL, and 816+/-66 pg/mL, respectively P=0.56). There was no significant correlation between H-FABP, free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in patients and controls. CONCLUSIONS: Serum H-FABP levels are not altered in patients with hyperthyroidism. PMID- 26859316 TI - Insertion of Cyclic Alkyl(amino) Carbene into the Si-H Bonds of Hydrochlorosilanes. AB - Carbenes are known for their ability to abstract HCl from hydrochlorosilanes to form carbene hydrochloride adducts. In contrast, the Si-H bond insertion products RSiCl2(cAACH) (2, 4, 6, and 8) have been formed in the reaction of RSiHCl2 [R = Ar(SiMe3)N (1), Cp* (3), PhC(NtBu)2 (5), Cl (7); Ar = 2,6-iPr2C6H3] with a cyclic alkyl(amino) carbene (cAAC:) irrespective of the steric demand of the R group. The new products have been characterized by various analytical tools including X ray crystallography, electron ionization mass spectrometry, and NMR spectroscopy. Theoretical investigations have also been performed to understand why cAAC prefers insertion into the Si-H bond rather than the dehydrohalogenation pathway. PMID- 26859317 TI - Hybrids of Two-Dimensional Ti3C2 and TiO2 Exposing {001} Facets toward Enhanced Photocatalytic Activity. AB - Effectively harvesting light to generate long-lived charge carriers to suppress the recombination of electrons and holes is crucial for photocatalytic reactions. Exposing the highly active facets has been regarded as a powerful approach to high-performance photocatalysts. Herein, a hybrid comprised of {001} facets of TiO2 nanosheets and layered Ti3C2, an emerging 2D material, was synthesized by a facile hydrothermal partial oxidation of Ti3C2. The in situ growth of TiO2 nanosheets on Ti3C2 allows for the interface with minimized defects, which was demonstrated by high-resolution transmission electron microscopy and density functional theory calculations. The highly active {001} facets of TiO2 afford high-efficiency photogeneration of electron-hole pairs, meanwhile the carrier separation is substantially promoted by the hole trapping effect by the interfacial Schottky junction with 2D Ti3C2 acting as a reservoir of holes. The improved charge separation and exposed active facets dramatically boost the photocatalytic degradation of methyl orange dye, showing the promise of 2D transition metal carbide for fabricating functional catalytic materials. PMID- 26859318 TI - Working conditions and occupational risk exposure in employees driving for work. AB - INTRODUCTION: An analysis of the occupational constraints and exposures to which employees facing road risk at work are subject was performed, with comparison versus non-exposed employees. Objective was to improve knowledge of the characteristics of workers exposed to road risk in France and of the concomitant occupational constraints. The descriptive study was based on data from the 2010 SUMER survey (Medical Monitoring of Occupational Risk Exposure: Surveillance Medicale des Expositions aux Risques professionnels), which included data not only on road risk exposure at work but also on a range of socio-occupational factors and working conditions. MATERIALS AND METHODS: The main variable of interest was "driving (car, truck, bus, coach, etc.) on public thoroughfares" for work (during the last week of work). This was a dichotomous "Yes/No" variable, distinguishing employees who drove for work; it also comprised 4-step weekly exposure duration: <2h, 2-10h, 10-20h and >=20h. RESULTS: 75% of the employees with driving exposure were male. Certain socio-occupational categories were found significantly more frequently: professional drivers (INSEE occupations and socio occupational categories (PCS) 64), skilled workers (PCS 61), intermediate professions and teaching, health, civil service (functionaries) and assimilated (PCS 46) and company executives (PCS 36). Employees with driving exposure more often worked in small businesses or establishments. Constraints in terms of schedule and work-time were more frequent in employees with driving exposure. Constraints in terms of work rhythm were more frequent in non-exposed employees, with the exception of external demands requiring immediate response. On the Karasek's Job Demand-Control Model, employees with driving exposure less often had low decision latitude. Prevalence of job-strain was also lower, as was prevalence of "iso-strain" (combination of job-strain and social isolation). Employees with driving exposure were less often concerned by hostile behavior and, when they did report such psychological violence (inspired on the Leymann questionnaire), it was significantly more frequently due to clients, users or patients. DISCUSSION: Employees with driving exposure at work showed several specificities. The present study, based on a representative nationwide survey of employees, confirmed the existence of differences in working conditions between employees with and without driving exposure at work. In employees with driving exposure, constraints in terms of work-time and rhythm increased with weekly exposure duration, as did tension at work and exposure to hostile behavior. PMID- 26859319 TI - A systematic review of psychosocial interventions for children and young people with epilepsy. AB - BACKGROUND: Despite recognition that psychosocial interventions can improve quality of life and mental health, there continues to be a lack of clarity and guidance around effective psychosocial interventions for children and young people with epilepsy. This review utilizes specific quality criteria to systematically identify and appraise the evidence for the effectiveness of psychosocial interventions for children and young people with epilepsy. METHODS: A systematic search of six electronic databases was conducted using predefined eligibility criteria. The reference lists of previous review papers were also manually searched. Seventeen studies met the inclusion and exclusion criteria. A quality appraisal checklist, the 'Crowe Critical Appraisal Tool' (CCAT) (Crowe, 2013) [1] was applied to the included articles, and effect sizes were calculated when not provided in the papers. RESULTS: Methodological quality of the majority of studies included was moderate, with only three studies rated as high quality. Meta-analysis was not conducted as the studies used heterogeneous methodologies and lacked consistency in outcome measures. Limited evidence was found for interventions improving epilepsy knowledge, quality of life, and psychological outcomes. CONCLUSIONS: Psychosocial interventions may provide clinical benefit although further research is needed to clarify the most effective treatment components, delivery methods, and measurement of intervention outcomes. The existing evidence base for children and young people is limited by methodological issues such as the use of small samples, inadequate power, and a lack of controlled studies. PMID- 26859320 TI - Cognitive impairment in older adults with epilepsy: Characterization and risk factor analysis. AB - OBJECTIVE: Cognitive deficits are common in epilepsy, though the impact of epilepsy on cognition in older adults is understudied. This study aimed to characterize cognition in older adults with epilepsy compared with healthy older adults and identify potential risk factors for impairment. METHODS: Thirty-eight older adults with epilepsy and 29 healthy controls completed a comprehensive neuropsychological battery, as well as measures of depression and anxiety. Chart review for current medications, seizure history, and neuroimaging was also completed. To compare cognitive performance between groups, ANOVA was used, and linear regression identified predictors of impairment among the group with epilepsy. RESULTS: Patients with epilepsy performed worse across nearly all cognitive domains, and were clinically impaired (i.e., >= 1.5 SD below mean) on more individual tests when compared with controls, including a subset of patients with epilepsy with normal MRIs. For all patients with epilepsy, taking a greater number of antiepileptic drugs was associated with poorer language and visuospatial abilities, and higher anxiety was associated with poorer visual memory. CONCLUSIONS: Older adults with epilepsy demonstrated greater cognitive deficits than matched controls. Polytherapy and anxiety heightened the risk for cognitive impairment in some cognitive domains, but not in others. Understanding the nature of cognitive decline in this population, as well as associated risk factors, may assist in the differential diagnosis of cognitive complaints and improve the design of treatment studies for older patients with epilepsy. Replication in larger, longitudinal studies is warranted to generalize these findings. PMID- 26859321 TI - CD3(+)/CD45(+) and SMA-alpha(+) circulating microparticles are increased in individuals at high cardiovascular risk who will develop a major cardiovascular event. PMID- 26859322 TI - A Trapped Covalent Intermediate of a Glycoside Hydrolase on the Pathway to Transglycosylation. Insights from Experiments and Quantum Mechanics/Molecular Mechanics Simulations. AB - The conversion of glycoside hydrolases (GHs) into transglycosylases (TGs), i.e., from enzymes that hydrolyze carbohydrates to enzymes that synthesize them, represents a promising solution for the large-scale synthesis of complex carbohydrates for biotechnological purposes. However, the lack of knowledge about the molecular details of transglycosylation hampers the rational design of TGs. Here we present the first crystallographic structure of a natural glycosyl-enzyme intermediate (GEI) of Saccharomyces cerevisiae Gas2 in complex with an acceptor substrate and demonstrate, by means of quantum mechanics/molecular mechanics metadynamics simulations, that it is tuned for transglycosylation (DeltaG(?) = 12 kcal/mol). The 2-OH...nucleophile interaction is found to be essential for catalysis: its removal raises the free energy barrier significantly (11 and 16 kcal/mol for glycosylation and transglycosylation, respectively) and alters the conformational itinerary of the substrate (from (4)C1 -> [(4)E](?) -> (1,4)B/(4)E to (4)C1 -> [(4)H3](?) -> (4)C1). Our results suggest that changes in the interactions involving the 2-position could have an impact on the transglycosylation activity of several GHs. PMID- 26859323 TI - Occlusion trajectory and a concept of a device for testing operating life of dentures. AB - PURPOSE: This paper presents an original method for the assessment of occlusion trajectory. On this basis, a special device for the assessment of operating life of dentures was designed. MATERIAL/METHODS: For this purpose, the SMART system by BTS for a comprehensive movement analysis was used. In order to analyze occlusion trajectory, characteristic points on patients' heads were appointed in which markers were placed, in accordance with the rules of measurement in dentistry. Markers' movement was recorded by means of 6 cameras, and then composition of coordinates was performed in a 3D system. RESULTS: In this way, curves representing movements of the characteristic points were plotted which, after the composition, with a considerable approximation, can be regarded as occlusion trajectory. CONCLUSIONS: On the basis of the obtained results, a thesis was put forward to the effect that traditional tribological testing machines based on systems of the pin-on-disc, ball-on-disc, etc. types, due to the simplicity of their working movements, are not adequately precise for the purpose of operational assessment of elements of prosthodontics. On this basis, a tribological node for a specialist testing machine for the assessment of operating life of dentures was designed. PMID- 26859325 TI - Nitrogen and phosphorus removal from tertiary wastewater in an osmotic membrane photobioreactor. AB - An osmotic membrane photobioreactor (OMPBR) was designed and operated for 162days for nitrogen and phosphorus removal from wastewater using Chlorella vulgaris. The removal efficiency for NH4(+)-N, NO3(-)-N and PO4(3-)-P reached as high as 95%, 53% and 89%, whereas the maximum removal rates were 3.41 mg/L-day, 0.20 mg/L-day and 0.8 mg/L-day, respectively. The microalgae exhibited high tendency to aggregate and attached to the bioreactor and membrane surfaces, and total biomass accumulation in the OMPBR was over 5 g/L. Salt accumulation and biofouling had adverse effects on membrane filtration, but the performance could be recovered through periodic backwashing of the membranes. Extracellular polymeric substances characterization indicated higher fraction of polysaccharides as compared to proteins. The biomass in the OMPBR accumulated higher levels of carbohydrates and chlorophyll. These results indicate the suitability of OMPBR in wastewater treatment and in high-density microalgae cultivation. PMID- 26859324 TI - Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry. AB - Aspirin and other nonsteroidal anti-inflammatory drugs target the cyclooxygenase enzymes (COX-1 and COX-2) to block the formation of prostaglandins. Aspirin is unique in that it covalently modifies each enzyme by acetylating Ser-530 within the cyclooxygenase active site. Acetylation of COX-1 leads to complete loss of activity, while acetylation of COX-2 results in the generation of the monooxygenated product 15(R)-hydroxyeicosatetraenoic acid (15R-HETE). Ser-530 has also been shown to influence the stereochemistry for the addition of oxygen to the prostaglandin product. We determined the crystal structures of S530T murine (mu) COX-2, aspirin-acetylated human (hu) COX-2, and huCOX-2 in complex with salicylate to 1.9, 2.0, and 2.4 A, respectively. The structures reveal that (1) the acetylated Ser-530 completely blocks access to the hydrophobic groove, (2) the observed binding pose of salicylate is reflective of the enzyme-inhibitor complex prior to acetylation, and (3) the observed Thr-530 rotamer in the S530T muCOX-2 crystal structure does not impede access to the hydrophobic groove. On the basis of these structural observations, along with functional analysis of the S530T/G533V double mutant, we propose a working hypothesis for the generation of 15R-HETE by aspirin-acetylated COX-2. We also observe differential acetylation of COX-2 purified in various detergent systems and nanodiscs, indicating that detergent and lipid binding within the membrane-binding domain of the enzyme alters the rate of the acetylation reaction in vitro. PMID- 26859327 TI - Techno-economic analysis of biofuel production considering logistic configurations. AB - In the study, a techno-economic analysis method considering logistic configurations is proposed. The economic feasibility of a low temperature biomass gasification pathway and an integrated pathway with fast pyrolysis and bio-oil gasification are evaluated and compared with the proposed method in Iowa. The results show that both pathways are profitable, biomass gasification pathway could achieve an Internal Rate of Return (IRR) of 10.00% by building a single biorefinery and integrated bio-oil gasification pathway could achieve an IRR of 3.32% by applying decentralized supply chain structure. A Monte-Carlo simulation considering interactions among parameters is also proposed and conducted, which indicates that both pathways are at high risk currently. PMID- 26859326 TI - HRT dependent performance and bacterial community population of granular hydrogen producing mixed cultures fed with galactose. AB - The effects of hydraulic retention times (HRTs-6, 3 and 2 h) on H2 production, operational stability and bacterial population response in a continuously stirred tank reactor (CSTR) were evaluated using galactose. A peak hydrogen production rate (HPR) of 25.9 L H2/L-d was obtained at a 3 h HRT with an organic loading rate (OLR) of 120 g/L-d, while the maximum hydrogen yield (HY) of 2.21 mol H2/mol galactose was obtained at a 6 h HRT (60 g galactose/L-d). Butyrate was dominant and the lactate concentration increased as HRT decreased, which significantly affected the HY. Biomass concentration (VSS) decreased from 16 to 3g/L at a 2 h HRT, leading to failure. A 3 h HRT supported the favorable growth of Clostridium species, as indicated by an increase in their populations from 25.4% to 27%, while significantly reducing Bacilli populations from 61.6% to 54.2%, indicating that this was the optimal condition. PMID- 26859328 TI - Solid acid-catalyzed depolymerization of barley straw driven by ball milling. AB - This study describes a time and energy saving, solvent-free procedure for the conversion of lignocellulosic barley straw into reducing sugars by mechanocatalytical pretreatment. The catalytic conversion efficiency of several solid acids was tested which revealed oxalic acid dihydrate as a potential catalyst with high conversion rate. Samples were mechanically treated by ball milling and subsequently hydrolyzed at different temperatures. The parameters of the mechanical treatment were optimized in order to obtain sufficient amount of total reducing sugar (TRS) which was determined following the DNS assay. Additionally, capillary electrophoresis (CE) and Fourier transform infrared spectrometry (FT-IR) were carried out. Under optimal conditions TRS 42% was released using oxalic acid dihydrate as a catalyst. This study revealed that the acid strength plays an important role in the depolymerization of barley straw and in addition, showed, that the oxalic acid-catalyzed reaction generates low level of the degradation product 5-hydroxymethylfurfural (HMF). PMID- 26859329 TI - Torrefaction of cultivation residue of Auricularia auricula-judae to obtain biochar with enhanced fuel properties. AB - Auricularia auricula-judae, commonly known as the wood ear, is a species of edible Auriculariales fungus. Torrefactions of cultivation residues of A. auricula-judae (CRAA) at different temperatures and residence times are carried out. Effect of different torrefaction conditions on the mass and energy yields, elemental composition, heating value, thermal properties; and chemical, crystal and morphological structures of biochars are analyzed. Low torrefaction temperatures could not enhance the fuel properties as expected. Crystallinities of biochars derived from mild torrefaction conditions do not have a suitable variation trend because of the unstable degrees between degradation and recrystallization. Torrefaction of CRAA should be processed under severe conditions, such as 320 degrees C for 60 min and 280 degrees C for 120 min, in order to obtain enhanced biochar properties with DTGmax at low peak temperatures of 367 and 361 degrees C, as well high burnout temperatures of 528 and 530 degrees C, respectively. PMID- 26859330 TI - Effective removal of heavy metal by biochar colloids under different pyrolysis temperatures. AB - Biochar colloids' association with heavy metal needs be studied to precisely evaluate the effectiveness of biochar as sorbents. The structure of biochar colloids and their roles in heavy metal removal were investigated by Fourier Transform Infrared Spectroscopy, X-ray Diffraction and batch adsorption experiments, respectively. Due to the numerous oxygen function groups and mineral matters contained in biochar colloids, the removal capacity of chromium (Cr) and cadmium (Cd) to biochar colloids was much greater than that of biochar residues. The highest adsorption capacities of Cr(III) and Cd(II) under initial pH 3.5 were obtained by RS400, which were mainly attributed to the presence of oxygen function groups and mineral matters simultaneously. The highest removal capacity of Cr(VI) was observed by RS300 due to the additional reduction by phenolic functional groups of RS300C. Therefore, the functions of biochar colloids for heavy metal removal should be considered. PMID- 26859331 TI - Separation of hemicellulose-derived saccharides from wood hydrolysate by lime and ion exchange resin. AB - A combined process of lime treatment and mixed bed ion exchange was proposed to separate hemicellulose-derived saccharides (HDS) from prehydrolysis liquor (PHL) of lignocellulose as value added products. The optimization of lime treatment achieved up to 44.2% removal of non-saccharide organic compounds (NSOC), mainly colloidal substances, with negligible HDS degradation at 0.5% lime level and subsequent neutralization by phosphoric acid. The residual NSOC and calcium ions in lime-treated PHL were eliminated by mixed bed ion exchange. The breakthrough curves of HDS and NSOC showed selective retention toward NSOC, leading to 75% HDS recovery with 95% purity at 17 bed volumes of exchange capacity. In addition, macroporous resin showed higher exchange capacity than gel resin as indicated by the triple processing volume. The remarkable selectivity of the combined process suggested the feasibility for HDS separation from PHL. PMID- 26859332 TI - PTHrP Nuclear Localization and Carboxyl Terminus Sequences Modulate Dental and Mandibular Development in Part via the Action of p27. AB - To determine whether the action of the PTHrP nuclear localization sequence and C terminus is mediated through p27 in modulating dental and mandibular development, compound mutant mice, which are homozygous for both p27 deletion and the PTHrP1 84 knock-in mutation (p27(-/-)Pthrp(KI/KI)), were generated. Their teeth and mandibular phenotypes were compared with those of p27(-/-), Pthrp(KI/KI), and wild-type mice. At 2 weeks of age, the mandibular mineral density, alveolar bone volume, osteoblast numbers, and dental volume, dentin sialoprotein-immunopositive areas in the first molar were increased significantly in p27(-/-) mice and decreased dramatically in both Pthrp(KI/KI) and p27(-/-) Pthrp(KI/KI) mice compared with wild-type mice; however, these parameters were partly rescued in p27(-/-) Pthrp(KI/KI) mice compared with Pthrp(KI/KI) mice. These data demonstrate that the deletion of p27 in Pthrp(KI/KI) mice can partially rescue defects in dental and mandibular development. Furthermore, we found that deletion of p27 in Pthrp(KI/KI) mice partially corrected the dental and mandibular phenotype by modulating cell cyclin-regulating molecules and antioxidant enzymes. This study therefore indicates that the p27 pathway may function downstream in the action of PTHrP nuclear localization sequence to regulate dental and mandibular development. PMID- 26859333 TI - Adipocyte Versus Somatotrope Leptin: Regulation of Metabolic Functions in the Mouse. AB - Leptin regulates food intake and energy expenditure (EE) and is produced in adipocytes, the pituitary, and several other tissues. Animals that are leptin or leptin receptor deficient have major metabolic complications, including obesity. This study tests the hypothesis that the pituitary somatotrope may contribute a source of leptin that maintains some of these metabolic functions. We created 2 different tissue-specific leptin knockout animals: a Somatotrope-Lep-null model and an Adipocyte-Lep-null model. Metabolic analysis of both models, along with a global deletion model, was performed. The Somatotrope-Lep-null animals had fewer somatotropes, and females had a 76% decrease in serum prolactin. During the dark (feeding) phase, females had a 35% increase in ambulation coupled with a 4% increase in EE. Mutants showed no change in food intake or weight gain and EE was unchanged in males. During the light (sleep) phase, Somatotrope-Lep-null mutant males had lower EE and females continued to have higher EE. The respiratory quotients (RQs) of mutants and littermate controls were decreased in males and increased in females; all were within the range that indicates predominant carbohydrate burning. The massively obese Adipocyte-Lep-null animals, however, had significant increases in food intake, sleep, and increased EE, with decreased activity. Changes in RQ were sexually dimorphic, with female mutants having higher RQ and males having decreased RQ. We conclude that both adipocyte and somatotrope leptin contribute to the metabolic homeostasis of the mouse, and that extraadipocyte sources of leptin cannot overcome the major metabolic challenges seen in these animals. PMID- 26859335 TI - Aortic Implantation for Anomalous Connection of the Coronary Artery to the Pulmonary Artery in Older Children and Adults. AB - Background Anomalous connection of the coronary artery to the pulmonary artery (ACAPA) has a low incidence rate in older children and adults. The aim of this article was to evaluate the outcome of treating ACAPA with aortic implantation in older children and adults. Methods We included 21 patients (9 children and 12 adults) with ACAPA in our hospital between January 1991 and January 2015. Among these patients, 19 had anomalous connection of the left coronary artery to the pulmonary artery, 2 had anomalous connection of the right coronary artery to the pulmonary artery (ARCAPA). All of the patients underwent aortic implantation, aged 4 to 62 years (median, 18). The mean left ventricular ejection fraction (LVEF) was 55.9 +/- 7.6% (<50% in 4). Eleven patients underwent direct aortic implantation (including two ARCAPAs), while 10 patients underwent tubular implantation. Eleven patients had varying degrees of mitral regurgitation, while mitral valve plasty or replacement was performed in six patients (severe mitral regurgitation) concurrently. Results There was no early mortality. Follow-up observation was performed in all 21 patients, with a mean follow-up time of 6.4 +/- 5.6 years (ranging from 0.5 to 23 years). Two patients died due to noncardiac reasons 1 and 10 years after operation, respectively. Seven patients had mild mitral regurgitation, while no patients had moderate or severe mitral regurgitation after operations. The postoperative mean LVEF was not improved at 54.7 +/- 7.0%, p > 0.05. Conclusion Among the multiple surgical strategies for the treatment of ACAPA, aortic implantation was used commonly in older children and adults, while mitral valve repair can be performed concurrently. PMID- 26859337 TI - Production and Photodissociation of the Methyl Perthiyl Radical. AB - The photodissociation dynamics of the methyl perthiyl (CH3SS) radical are investigated via molecular beam photofragment translational spectroscopy, using "soft" electron ionization to detect the radicals and their photofragments. With this new capability, we have shown that CH3SS can be generated from flash pyrolysis of dimethyl trisulfide. Utilizing this source of radicals and the advantages afforded by soft electron ionization, we have reinvestigated the photodissociation dynamics of CH3SS at 248 nm, finding CH3S + S to be the dominant dissociation channel with CH3 + SS as a minor process. These results differ from previous work reported in our laboratory in which we found CH3 + SS and CH2S + SH as the main dissociation channels. The difference in results is discussed in light of our new capabilities for characterization of radical production. PMID- 26859336 TI - Ultralow dose dentomaxillofacial CT imaging and iterative reconstruction techniques: variability of Hounsfield units and contrast-to-noise ratio. AB - OBJECTIVE: The aim of this study was to evaluate whether application of ultralow dose protocols and iterative reconstruction technology (IRT) influence quantitative Hounsfield units (HUs) and contrast-to-noise ratio (CNR) in dentomaxillofacial CT imaging. METHODS: A phantom with inserts of five types of materials was scanned using protocols for (a) a clinical reference for navigated surgery (CT dose index volume 36.58 mGy), (b) low-dose sinus imaging (18.28 mGy) and (c) four ultralow dose imaging (4.14, 2.63, 0.99 and 0.53 mGy). All images were reconstructed using: (i) filtered back projection (FBP); (ii) IRT: adaptive statistical iterative reconstruction-50 (ASIR-50), ASIR-100 and model-based iterative reconstruction (MBIR); and (iii) standard (std) and bone kernel. Mean HU, CNR and average HU error after recalibration were determined. Each combination of protocols was compared using Friedman analysis of variance, followed by Dunn's multiple comparison test. RESULTS: Pearson's sample correlation coefficients were all >0.99. Ultralow dose protocols using FBP showed errors of up to 273 HU. Std kernels had less HU variability than bone kernels. MBIR reduced the error value for the lowest dose protocol to 138 HU and retained the highest relative CNR. ASIR could not demonstrate significant advantages over FBP. CONCLUSIONS: Considering a potential dose reduction as low as 1.5% of a std protocol, ultralow dose protocols and IRT should be further tested for clinical dentomaxillofacial CT imaging. ADVANCES IN KNOWLEDGE: HU as a surrogate for bone density may vary significantly in CT ultralow dose imaging. However, use of std kernels and MBIR technology reduce HU error values and may retain the highest CNR. PMID- 26859340 TI - Improved survival of colorectal cancer in Denmark during 2001-2012 - The efforts of several national initiatives. AB - Background The Danish Colorectal Cancer Group (DCCG) established a national clinical database in 2001 with the aim to monitor and improve outcome of colorectal cancer patients. Since 2000 several national initiatives have been taken to improve cancer outcome. In the present study we used DCCG data to evaluate mortality and survival of CRC patients with focus on comorbidity, stage, and perioperative treatment. Material and methods Patients notified to the DCCG database from 2001 to 2012 were included. Patients with primary cancer of the colon and rectum were analyzed separately. Analyses were stratified according to gender, comorbidity, Union for International Cancer Control (UICC) stage, and operative priority (elective/emergency/no surgery). Data were stratified into three time periods (2001-2004, 2005-2008, 2009-2012). Mortality and survival were age adjusted. Results In total 29 385 patients with colon cancer and 15 213 patients with rectal cancer were included. The stage distribution was almost stable over time. The mortality rate per 100 patient year within one year decreased from 32 to 26 in colon cancer and from 26 to 19 in rectal cancer with associated improvements in absolute survival from 73% to 78% in colon cancer and from 78% to 83% in rectal cancer. The five-year relative survival of colon cancer improved from 58% to 63% and in rectal cancer from 59% to 65%. Comorbidity had major negative impact on outcome. Irrespective of tumor location, outcome improved relatively more in patients with stage III and IV disease. The proportion of patients who were spared surgery increased from 8% to 15% in colon cancer and from 13% to 19% in rectal cancer, and these changes were associated with improved outcome for rectal cancer patients, whereas outcome worsened for colon cancer patients. Conclusion The Danish efforts to improve outcome of cancer have succeeded with improved outcomes in patients with colorectal cancer. PMID- 26859334 TI - Developmental Programming, a Pathway to Disease. AB - Accumulating evidence suggests that insults occurring during the perinatal period alter the developmental trajectory of the fetus/offspring leading to long-term detrimental outcomes that often culminate in adult pathologies. These perinatal insults include maternal/fetal disease states, nutritional deficits/excess, stress, lifestyle choices, exposure to environmental chemicals, and medical interventions. In addition to reviewing the various insults that contribute to developmental programming and the benefits of animal models in addressing underlying mechanisms, this review focuses on the commonalities in disease outcomes stemming from various insults, the convergence of mechanistic pathways via which various insults can lead to common outcomes, and identifies the knowledge gaps in the field and future directions. PMID- 26859341 TI - Comparison of decoding resolution of standard and high-density electrocorticogram electrodes. AB - OBJECTIVE: Electrocorticography (ECoG)-based brain-computer interface (BCI) is a promising platform for controlling arm prostheses. To restore functional independence, a BCI must be able to control arm prostheses along at least six degrees-of-freedoms (DOFs). Prior studies suggest that standard ECoG grids may be insufficient to decode multi-DOF arm movements. This study compared the ability of standard and high-density (HD) ECoG grids to decode the presence/absence of six elementary arm movements and the type of movement performed. APPROACH: Three subjects implanted with standard grids (4 mm diameter, 10 mm spacing) and three with HD grids (2 mm diameter, 4 mm spacing) had ECoG signals recorded while performing the following movements: (1) pincer grasp/release, (2) wrist flexion/extension, (3) pronation/supination, (4) elbow flexion/extension, (5) shoulder internal/external rotation, and (6) shoulder forward flexion/extension. Data from the primary motor cortex were used to train a state decoder to detect the presence/absence of movement, and a six-class decoder to distinguish between these movements. MAIN RESULTS: The average performances of the state decoders trained on HD ECoG data were superior (p = 3.05 * 10(-5)) to those of their standard grid counterparts across all combinations of the MU, beta, low-gamma, and high-gamma frequency bands. The average best decoding error for HD grids was 2.6%, compared to 8.5% of standard grids (chance 50%). The movement decoders trained on HD ECoG data were superior (p = 3.05 * 10(-5)) to those based on standard ECoG across all band combinations. The average best decoding errors of 11.9% and 33.1% were obtained for HD and standard grids, respectively (chance error 83.3%). These improvements can be attributed to higher electrode density and signal quality of HD grids. SIGNIFICANCE: Commonly used ECoG grids are inadequate for multi-DOF BCI arm prostheses. The performance gains by HD grids may eventually lead to independence-restoring BCI arm prosthesis. PMID- 26859342 TI - Depressive symptoms in midlife: the role of reproductive stage. AB - OBJECTIVE: The aim of the study was to determine the prevalence of depression among community-dwelling women in the premenopause, menopausal transition (MT), and postmenopause stage. We also sought to clarify the direct and indirect contribution of menopausal status on the risk of depression. METHODS: Cross sectional survey of 1,612 women aged 45 to 55 years living in the Perth metropolitan region, who were recruited using a random sample of the electoral roll (voting is compulsory in Australia), was conducted. Women with clinically significant symptoms of depression had Patient Health Questionnaire (PHQ-9) scores of at least 10, and those with major depression, reported symptoms consistent with Diagnostic and Statistical Manual of Mental Disorders, 5th ed (DSM-5), criteria. We used past and current gynecological and reproductive data to classify women as premenopausal, undergoing the MT, and postmenopausal. Other study measures included age, place of birth, education, marital status, drinking habit, number of children, medical illnesses, and history of premenstrual syndrome, postnatal depression, and past depression or anxiety. We investigated the direct and indirect effect of reproductive status with mediation/modulation analysis. RESULTS: Among the women included in the survey, 8.2%, 11.5%, and 13.0% of women in premenopause, MT, and postmenopause had PHQ-9 at least 10, whereas major depression was present in 2.2%, 3.4%, and 3.6% of them. Reproductive status did not affect the prevalence of major depression, but more postmenopausal than premenopausal women had PHQ-9 score equal to or greater than 10 (P = 0.013). Compared with premenopausal women, MT was associated with a direct odds ratio (OR) 1.35 (95% confidence interval [CI] = 0.90, 2.01) and indirect OR 1.08 (95% CI = 0.92, 1.26) for PHQ-9 at least 10. Similarly, the direct and indirect effect of the postmenopause on the odds of PHQ-9 at least 10 was OR 1.31 (95% CI = 0.87, 1.98) and OR 1.29 (95% CI = 1.10, 1.52). CONCLUSIONS: The slight, but not significant, excess of depressive symptoms during MT and early postmenopause cannot be attributed to a direct effect of reproductive status. PMID- 26859344 TI - Resident education in menopause: why it is important and how we can best achieve it. PMID- 26859345 TI - Is vaginal administration the "way out" of the hormone of controversy? PMID- 26859343 TI - Effects of vitamin D supplementation during weight loss on sex hormones in postmenopausal women. AB - OBJECTIVE: The aim of the study was to compare the effects of vitamin D3 supplementation versus placebo on serum sex hormones in postmenopausal women completing a 12-month diet + exercise weight loss program. METHODS: Two hundred eighteen overweight or obese women (50-75 y) with serum 25-hydroxyvitamin D at least 10 to less than 32 ng/mL ("insufficient") were randomized to either weight loss + 2,000 IU/day oral vitamin D3, or to weight loss + daily placebo. Serum sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone were measured by radioimmunoassay before randomization and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations. RESULTS: The 12-month changes in sex hormone binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone did not differ between groups (all P > 0.05). However, a greater increase in serum 25-hydroxyvitamin D was associated with a greater increase in sex hormone-binding globulin (Ptrend = 0.01), and larger decreases in free and bioavailable estradiol (Ptrend = 0.04, Ptrend = 0.03, respectively). In post-hoc analyses, we compared women randomized to vitamin D whose serum 25-hydroxyvitamin D remained insufficient (n = 38), to women who became replete (25-hydroxyvitamin D >=32 ng/mL; n = 53). Replete women showed greater reductions in bioavailable estradiol (-1.8 vs -0.7 pg/mL), free testosterone (-0.8 vs -0.3 pg/mL), and bioavailable testosterone (-1.8 vs -0.6 ng/dL), and a greater increase in sex hormone-binding globulin (10.6 vs 4.7 nmol/L) (all P < 0.05), even after adjusting for differences in total 12-month weight loss. CONCLUSIONS: Overall, 12 month changes in sex hormone did not differ between groups. However, vitamin D repletion was associated with greater reductions in sex hormones during weight loss, with a possible dose-dependent effect. Future studies should test higher doses and target circulating 25-hydroxyvitamin D levels when measuring such effects. PMID- 26859346 TI - Moss tasiRNAs Make the Auxin Network Robust. AB - The TAS3 tasiRNA pathway has been coopted to regulate diverse developmental processes in plants. In this issue of Developmental Cell, Plavskin et al. (2016) explore the role of the pathway in the moss Physcomitrella patens. Their results suggest that frequent cooption may be related to unique qualities of tasiRNA mediated regulation. PMID- 26859347 TI - TBX5 and NuRD Divide the Heart. AB - In this issue of Developmental Cell, Waldron et al. (2016) identify an interaction between a master regulator of heart development, TBX5, and the NuRD complex and describe how mutations affecting the interaction may contribute to congenital heart disease. Furthermore, these interactions may have contributed to the evolution of cardiac septation. PMID- 26859348 TI - Bigger Isn't Always Better: Cell Size and the Spindle Assembly Checkpoint. AB - Variation in the activity of the spindle assembly checkpoint has been observed in different cell types, yet the reason for this variability remains poorly understood. Reporting in Developmental Cell, Galli and Morgan (2016) show that checkpoint activity increases during development as cell size, and the cytoplasm to-kinetochore ratio, decreases. PMID- 26859349 TI - How Toll Met Hippo. AB - Toll and Hippo are two seemingly disparate pathways that regulate innate immunity and tissue growth, respectively. Reporting recently in Cell, Liu et al. (2016) tie them together by demonstrating that microbial infection activates Toll, which then signals to both pathways to modulate the antimicrobial response. PMID- 26859350 TI - Cell Division Drives Epithelial Cell Rearrangements during Gastrulation in Chick. AB - During early embryonic development, cells are organized as cohesive epithelial sheets that are continuously growing and remodeled without losing their integrity, giving rise to a wide array of tissue shapes. Here, using live imaging in chick embryo, we investigate how epithelial cells rearrange during gastrulation. We find that cell division is a major rearrangement driver that powers dramatic epithelial cell intercalation events. We show that these cell division-mediated intercalations, which represent the majority of epithelial rearrangements within the early embryo, are absolutely necessary for the spatial patterning of gastrulation movements. Furthermore, we demonstrate that these intercalation events result from overall low cortical actomyosin accumulation within the epithelial cells of the embryo, which enables dividing cells to remodel junctions in their vicinity. These findings uncover a role for cell division as coordinator of epithelial growth and remodeling that might underlie various developmental, homeostatic, or pathological processes in amniotes. PMID- 26859353 TI - Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis. AB - Chromosomal instability (CIN) is thought to be a source of mutability in cancer. However, CIN often results in aneuploidy, which compromises cell fitness. Here, we used the dosage compensation mechanism (DCM) of Drosophila to demonstrate that chromosome-wide gene dosage imbalance contributes to the deleterious effects of CIN-induced aneuploidy and its pro-tumorigenic action. We present evidence that resetting of the DCM counterbalances the damaging effects caused by CIN-induced changes in X chromosome number. Importantly, interfering with the DCM suffices to mimic the cellular effects of aneuploidy in terms of reactive oxygen species (ROS) production, JNK-dependent cell death, and tumorigenesis upon apoptosis inhibition. We unveil a role of ROS in JNK activation and a variety of cellular and tissue-wide mechanisms that buffer the deleterious effects of CIN, including DNA-damage repair, activation of the p38 pathway, and cytokine induction to promote compensatory proliferation. Our data reveal the existence of robust compensatory mechanisms that counteract CIN-induced cell death and tumorigenesis. PMID- 26859352 TI - Ancient trans-Acting siRNAs Confer Robustness and Sensitivity onto the Auxin Response. AB - Novel developmental programs often evolve via cooption of existing genetic networks. To understand this process, we explored cooption of the TAS3 tasiRNA pathway in the moss Physcomitrella patens. We find an ancestral function for this repeatedly redeployed pathway in the spatial regulation of a conserved set of Auxin Response Factors. In moss, this results in stochastic patterning of the filamentous protonemal tissue. Through modeling and experimentation, we demonstrate that tasiRNA regulation confers sensitivity and robustness onto the auxin response. Increased auxin sensitivity parallels increased developmental sensitivity to nitrogen, a key environmental signal. We propose that the properties lent to the auxin response network, along with the ability to stochastically modulate development in response to environmental cues, have contributed to repeated cooption of the tasiRNA-ARF module during evolution. The signaling properties of a genetic network, and not just its developmental output, are thus critical to understanding evolution of multicellular forms. PMID- 26859351 TI - The Cardiac TBX5 Interactome Reveals a Chromatin Remodeling Network Essential for Cardiac Septation. AB - Human mutations in the cardiac transcription factor gene TBX5 cause congenital heart disease (CHD), although the underlying mechanism is unknown. We report characterization of the endogenous TBX5 cardiac interactome and demonstrate that TBX5, long considered a transcriptional activator, interacts biochemically and genetically with the nucleosome remodeling and deacetylase (NuRD) repressor complex. Incompatible gene programs are repressed by TBX5 in the developing heart. CHD mis-sense mutations that disrupt the TBX5-NuRD interaction cause depression of a subset of repressed genes. Furthermore, the TBX5-NuRD interaction is required for heart development. Phylogenetic analysis showed that the TBX5 NuRD interaction domain evolved during early diversification of vertebrates, simultaneous with the evolution of cardiac septation. Collectively, this work defines a TBX5-NuRD interaction essential to cardiac development and the evolution of the mammalian heart, and when altered may contribute to human CHD. PMID- 26859354 TI - Hdac3 Interaction with p300 Histone Acetyltransferase Regulates the Oligodendrocyte and Astrocyte Lineage Fate Switch. AB - Establishment and maintenance of CNS glial cell identity ensures proper brain development and function, yet the epigenetic mechanisms underlying glial fate control remain poorly understood. Here, we show that the histone deacetylase Hdac3 controls oligodendrocyte-specification gene Olig2 expression and functions as a molecular switch for oligodendrocyte and astrocyte lineage determination. Hdac3 ablation leads to a significant increase of astrocytes with a concomitant loss of oligodendrocytes. Lineage tracing indicates that the ectopic astrocytes originate from oligodendrocyte progenitors. Genome-wide occupancy analysis reveals that Hdac3 interacts with p300 to activate oligodendroglial lineage specific genes, while suppressing astroglial differentiation genes including NFIA. Furthermore, we find that Hdac3 modulates the acetylation state of Stat3 and competes with Stat3 for p300 binding to antagonize astrogliogenesis. Thus, our data suggest that Hdac3 cooperates with p300 to prime and maintain oligodendrocyte identity while inhibiting NFIA and Stat3-mediated astrogliogenesis, and thereby regulates phenotypic commitment at the point of oligodendrocyte-astrocytic fate decision. PMID- 26859355 TI - Phosphorylation-Dependent Activation of the ESCRT Function of ALIX in Cytokinetic Abscission and Retroviral Budding. AB - The modular adaptor protein ALIX is a key player in multiple ESCRT-III-mediated membrane remodeling processes. ALIX is normally present in a closed conformation due to an intramolecular interaction that renders ALIX unable to perform its ESCRT functions. Here we demonstrate that M phase-specific phosphorylation of the intramolecular interaction site within the proline-rich domain (PRD) of ALIX transforms cytosolic ALIX from closed to open conformation. Defining the role of this mechanism of ALIX regulation in three classical ESCRT-mediated processes revealed that phosphorylation of the intramolecular interaction site in the PRD is required for ALIX to function in cytokinetic abscission and retroviral budding, but not in multivesicular body sorting of activated epidermal growth factor receptor. Thus, phosphorylation of the intramolecular interaction site in the PRD is one of the major mechanisms that activates the ESCRT function of ALIX. PMID- 26859356 TI - Cell Size Determines the Strength of the Spindle Assembly Checkpoint during Embryonic Development. AB - The spindle assembly checkpoint (SAC) delays mitotic progression when chromosomes are not properly attached to microtubules of the mitotic spindle. Cells vary widely in the extent to which they delay mitotic progression upon SAC activation. To explore the mechanisms that determine checkpoint strength in different cells, we systematically measured the mitotic delay induced by microtubule disruption at different stages of embryogenesis in Caenorhabditis elegans. Strikingly, we observed a gradual increase in SAC strength after each round of division. Analysis of mutants that alter cell size or ploidy revealed that SAC strength is determined primarily by cell size and the number of kinetochores. These findings provide clear evidence in vivo that the kinetochore-to-cytoplasm ratio determines the strength of the SAC, providing new insights into why cells exhibit such large variations in their SAC responses. PMID- 26859357 TI - A Comparison of Sequential Glaucoma Drainage Device Implantation Versus Cyclophotocoagulation Following Failure of a Primary Drainage Device. AB - PURPOSE: To compare sequential glaucoma drainage device (GDD) implantation with transscleral diode cyclophotocoagulation (CPC) following failure of a primary GDD. MATERIALS AND METHODS: A retrospective review of all patients who underwent GDD implantation at a single institution over 10 years. Patients who required an additional GDD and/or CPC were analyzed. Success was defined as absence of loss of light perception, reoperation for glaucoma, and intraocular pressure (IOP) >21 or <6 at 2 consecutive visits after an initial 3-month period. RESULTS: Thirty two patients received sequential GDD. Twenty-one underwent CPC. Cohorts were statistically similar in regards to age, sex, race, and number of previous surgeries. Preoperatively, the GDD cohort had a lower IOP and better visual acuity. The mean length of follow-up was 37.9 months for the GDD group and 46.3 months for CPC. Both procedures significantly reduced IOP; however, CPC led to a greater reduction (P=0.0172). Survival analysis found the 5-year probability of surgical success to be 65.3% for sequential GDD and 58.0% for CPC (P=0.8678). No cases of phthisis occurred in either group. There were 2 cases of endophthalmitis (6.3%) in the GDD group, and none in the CPC group. In eyes without preexisting corneal edema, estimated corneal decompensation probability at 3 years was 31.6% for GDD and 6.7% for CPC (P=0.0828). CONCLUSIONS: Sequential GDD and CPC are both effective at reducing IOP following the failure of a primary GDD. CPC after GDD failure warrants further investigation as it led to a greater reduction in IOP with fewer serious adverse events. PMID- 26859358 TI - Lamina Cribrosa Depth is Associated With the Cup-to-Disc Ratio in Eyes With Large Optic Disc Cupping and Cup-to-Disc Ratio Asymmetry. AB - PURPOSE: To investigate the lamina cribrosa (LC) depth and its relationship with the cup-to-disc ratio (CDR) in the eyes with generalized increased optic disc cupping and CDR asymmetry. METHODS: Glaucoma suspect subjects with a CDR>=0.7, CDR asymmetry >=0.2 in the absence of visual field (VF) loss, and normal control subjects were enrolled. The optic nerve head was imaged using the enhanced depth imaging modes of Spectralis optical coherence tomography. The LC depth was determined at the mid-horizontal, and the superior and inferior mid-peripheral regions of the optic nerve head. RESULTS: Disc area and CDRs were larger in the glaucoma suspect group compared with the control group (P<0.001). The mean LC depth was significantly greater in the disc area-matched glaucoma suspect group compared with the normal control group (P<0.001). The mean LC depth was positively correlated with the average and vertical CDRs (r=0.755 and 0.664, respectively; both P<0.001), which was maintained after controlling for the disc area (r=0.756 and 0.645, respectively; both P<0.001). In eyes with CDR asymmetry, the LC was located more posteriorly in eyes with a higher CDR compared with fellow eyes with a lower CDR (P<0.001). CONCLUSIONS: The LC depth was greater in eyes with generalized increased cupping, as well as in eyes with a higher CDR than fellow eyes, and was significantly related to the CDR. These results suggest that the clinical appearance of cup enlargement or cupping has LC displacement components. PMID- 26859359 TI - The Conjunctiva in Normal Tension Glaucoma Patients is Thinner Than in Primary Open-Angle Glaucoma Patients: A Comparative Histologic Study. AB - PURPOSE: To compare histologically the thickness of conjunctival specimens of normal tension glaucoma (NTG) patients with primary open-angle glaucoma (POAG) patients. MATERIALS AND METHODS: In this prospective study, 54 patients scheduled for trabeculectomy were categorized into NTG and POAG based on their maximum untreated intraocular pressure at any time (IOPmax) as measured by Goldmann applanation tonometry. Sixteen patients with NTG (IOPmax<=21 mm Hg) and 36 patients with high tension POAG (IOPmax>21 mm Hg) were included in the study. Biopsies were taken from the superior bulbar conjunctiva during trabeculectomy. The specimens were fixed in formalin, embedded in methacrylate, histologically sectioned, stained with toluidine blue, and analyzed with a light microscope. The stromal conjunctival thickness (CT) was measured in a standardized way and compared between the 2 groups. Intergroup comparisons were performed using the Mann-Whitney U test for continuous variables and the Fisher exact test for categorical variables. The correlation between the central cornea thickness (CCT) and the CT was investigated by the Spearman test. RESULTS: The stromal CT was significantly thinner in NTG compared with POAG (64+/-31 vs. 103+/-44 um, respectively; P=0.002). Stromal CT of the whole group was positively correlated with IOPmax (r=0.41; P=0.002; 95% confidence interval, 0.15-0.62) but not with central cornea thickness (r=-0.005; P=0.97; 95% confidence interval, -0.28 to 0.27). CONCLUSIONS: The conjunctiva in patients with NTG was thinner than in POAG patients. This finding is an additional feature in the pattern of thinner ocular structures in patients with NTG. PMID- 26859360 TI - Accuracy of Measurements With the iCare HOME Rebound Tonometer. AB - PURPOSE: To evaluate the accuracy of intraocular pressure (IOP) measurements obtained with the newly available iCare HOME (RTHOME) rebound tonometer compared with the iCare ONE (RTONE) tonometer and Goldmann applanation tonometry (GAT), and possible correlation with central corneal thickness (CCT). MATERIALS AND METHODS: IOP measurements were obtained from 154 patients by an ophthalmologist (doc) using each of the above-mentioned tonometers. In addition, patients (pat) measured their own IOP with the RTHOME and RTONE. The means and SD of results obtained with the different tonometers were compared. Agreement between the tonometers was calculated using the Bland-Altman method. RESULTS: Mean IOPs for the right eyes only were 15.9+/-6.4 mm Hg (RTONEdoc), 15.8+/-6.4 mm Hg (RTONEpat), 15.0+/-5.9 mm Hg (RTHOMEdoc), 14.9+/-6.3 mm Hg (RTHOMEpat), and 15.8+/-4.4 mm Hg (GAT). Bland-Altman analysis revealed mean differences (bias) between RTONEdoc and RTHOMEdoc, between RTHOMEdoc and RTHOMEpat, and between RTHOMEdoc and GAT of 0.8, 0.1, and -0.8 mm Hg, respectively, with 95% limits of agreement of -3.5 to 5.2, -4.9 to 5.1, and -7.2 to 5.6 mm Hg, respectively. Linear regression of the comparisons revealed a proportional error over the range of pressures examined in the case of RTHOMEdoc versus GAT (slope=0.32, P<0.001). Considering the data from all eyes, the difference between RTHOMEdoc and GAT correlated significantly with the CCT (P=0.01). CONCLUSION: RTHOME readings correlate well with the GAT results although some limitations such as dependency of readings on CCT and increasing differences at lower and higher IOP levels need to be taken into account. PMID- 26859362 TI - Fos-Zippered GH Receptor Cytosolic Tails Act as Jak2 Substrates and Signal Transducers. AB - Members of the Janus kinase (Jak) family initiate the majority of downstream signaling events of the cytokine receptor family. The prevailing principle is that the receptors act in dimers: 2 Jak2 molecules bind to the cytosolic tails of a cytokine receptor family member and initiate Jak-signal transducer and activator of transcription signaling upon a conformational change in the receptor complex, induced by the cognate cytokine. Due to the complexity of signaling complexes, there is a strong need for in vitro model systems. To investigate the molecular details of the Jak2 interaction with the GH receptor (GHR), we used cytosolic tails provided with leucine zippers derived from c-Fos to mimic the dimerized state of GHR. Expressed together with Jak2, fos-zippered tails, but not unzippered tails, were stabilized. In addition, the Jak-signal transducer and activator of transcription signaling pathway was activated by the fos-zippered tails. The stabilization depended also on alpha-helix rotation of the zippers. Fos-zippered GHR tails and Jak2, both purified from baculovirus-infected insect cells, interacted via box1 with a binding affinity of approximately 40nM. As expected, the Jak kinase inhibitor Ruxolitinib inhibited the stabilization but did not affect the c-Fos-zippered GHR tail-Jak2 interaction. Analysis by blue native gel electrophoresis revealed high molecular-weight complexes containing both Jak2 and nonphosphorylated GHR tails, whereas Jak2-dissociated tails were highly phosphorylated and monomeric, implying that Jak2 detaches from its substrate upon phosphorylation. PMID- 26859361 TI - Hexim1, a Novel Regulator of Leptin Function, Modulates Obesity and Glucose Disposal. AB - Leptin triggers signaling events with significant transcriptional responses that are essential to metabolic processes affecting obesity and glucose disposal. We asked whether hexamethylene bis-acetamide inducible-1 (Hexim1), an inhibitor of RNA II polymerase-dependent transcription elongation, regulates leptin-Janus kinase 2 signaling axis in the hypothalamus. We subjected C57BL6 Hexim1 heterozygous (HT) mice to high-fat diet and when compared with wild type, HT mice were resistant to high-fat diet-induced weight gain and remain insulin sensitive. HT mice exhibited increased leptin-pY(705)Stat3 signaling in the hypothalamus, with normal adipocyte size, increased type I oxidative muscle fiber density, and enhanced glucose transporter 4 expression. We also observed that normal Hexim1 protein level is required to facilitate the expression of CCAAT/enhancer-binding proteins (C/EBPs) required for adipogenesis and inducible suppressor of cytokine signaling 3 (SOCS) expression. Further support on the role of Hexim1 regulating C/EBPs during adipocyte differentiation was shown when HT 3T3L1 fibroblasts failed to undergo adipogenesis. Hexim1 selectively modulates leptin-mediated signal transduction pathways in the hypothalamus, the expression of C/EBPs and peroxisome proliferator-activated receptor-gamma (PPAR gamma) in skeletal muscle and adipose tissue during the adaptation to metabolic stress. We postulate that Hexim1 might be a novel factor involved in maintaining whole-body energy balance. PMID- 26859363 TI - Physiological adjustment to postnatal growth trajectories in healthy preterm infants. AB - BACKGROUND: International guidelines suggest that growth of preterm infants should match intrauterine rates. However, the trajectory for extrauterine growth may deviate from the birth percentile due to an irreversible, physiological loss of extracellular fluid during postnatal adaptation to extrauterine conditions. To which "new" physiological growth trajectory preterm infants should adjust to after completed postnatal adaptation is unknown. This study analyzes the postnatal growth trajectories of healthy preterm infants using prospective criteria defining minimal support, as a model for physiological adaptation. METHODS: International, multi-center, longitudinal, observational study at five neonatal intensive care units (NICUs). Daily weights until day of life (DoL) 21 of infants with undisturbed postnatal adaptation were analyzed (gestational ages: (i) 25-29 wk, (ii) 30-34 wk). RESULTS: 981 out of 3,703 admitted infants included. Maximum weight loss was 11% (i) and 7% (ii) by DoL 5, birth weight regained by DoL 15 (i) and 13 (ii). Infants transitioned to growth trajectories parallel to Fenton chart percentiles, 0.8 z-scores below their birth percentiles. The new trajectory after completed postnatal adaptation could be predicted for DoL 21 with R(2) = 0.96. CONCLUSION: This study provides a robust estimate for physiological growth trajectories of infants after undisturbed postnatal adaptation. In the future, the concept of a target postnatal trajectory during NICU care may be useful. PMID- 26859364 TI - Smad7 interrupts TGF-beta signaling in intestinal macrophages and promotes inflammatory activation of these cells during necrotizing enterocolitis. AB - BACKGROUND: Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants. Based on our recent findings of increased Smad7 expression in surgically resected bowel affected by NEC, we hypothesized that NEC macrophages undergo inflammatory activation because increased Smad7 expression renders these cells resistant to normal, gut-specific, transforming growth factor (TGF)-beta mediated suppression of inflammatory pathways. METHODS: We used surgically resected human NEC tissue, murine models of NEC-like injury, bone marrow-derived and intestinal macrophages, and RAW264.7 cells. Smad7 and IkappaB kinase-beta (IKK-beta) were measured by quantitative PCR, western blots, and immunohistochemistry. Promoter activation was confirmed in luciferase reporter and chromatin immunoprecipitation assays. RESULTS: NEC macrophages showed increased Smad7 expression, particularly in areas with severe tissue damage and high bacterial load. Lipopolysaccharide-induced Smad7 expression suppressed TGF beta signaling and augmented nuclear factor-kappa B (NF-kappaB) activation and cytokine production in macrophages. Smad7-mediated NF-kappaB activation was likely mediated via increased expression of IKK-beta, which, further increased Smad7 expression in a feed-forward loop. We show that Smad7 induced IKK-beta expression through direct binding to the IKK-beta promoter and its transcriptional activation. CONCLUSION: Smad7 expression in NEC macrophages interrupts TGF-beta signaling and promotes NF-kappaB-mediated inflammatory signaling in these cells through increased expression of IKK-beta. PMID- 26859365 TI - Baroreflex dysfunction in sick newborns makes heart rate an unreliable surrogate for blood pressure changes. AB - BACKGROUND: Cerebral pressure passivity (CPP) in sick newborns can be detected by evaluating coupling between mean arterial pressure (MAP) and cerebral blood flow measured by near infra-red spectroscopy hemoglobin difference (HbD). However, continuous MAP monitoring requires invasive catheterization with its inherent risks. We tested whether heart rate (HR) could serve as a reliable surrogate for MAP in the detection of CPP in sick newborns. METHODS: Continuous measurements of MAP, HR, and HbD were made and partitioned into 10-min epochs. Spectral coherence (COH) was computed between MAP and HbD (COHMAP-HbD) to detect CPP, between HR and HbD (COHHR-HbD) for comparison, and between MAP and HR (COHMAP-HR) to quantify baroreflex function (BRF). The agreement between COHMAP-HbD and COHHR-HbD was assessed using ROC analysis. RESULTS: We found poor agreement between COHMAP-HbD and COHHR-HbD in left hemisphere (area under the ROC curve (AUC) 0.68) and right hemisphere (AUC 0.71). Baroreflex failure (COHMAP-HR not significant) was present in 79% of epochs. Confining comparison to epochs with intact BRF showed an AUC of 0.85 for both hemispheres. CONCLUSIONS: In these sick newborns, HR was an unreliable surrogate for MAP required for the detection of CPP. This is likely due to the prevalence of BRF failure in these infants. PMID- 26859367 TI - Timing of allergen exposure and the development of food allergy: treating before the horse is out of the barn. AB - PURPOSE OF REVIEW: Until recently, nutritional guidelines did not support early introduction of allergenic foods into the diet of high-risk infants. Following recent studies, this approach is beginning to change, at least for peanuts. This review will examine the change in nutritional guidelines and the scientific data that led to these changes. RECENT FINDING: In a recent prospective controlled study, regular consumption of peanut protein in infants from 4-11 months of age with atopic dermatitis or egg allergy, was associated with lower prevalence of peanut allergy (1.9%) at 60 months of age compared with peanut avoidance (13.7%). Other studies demonstrated that earlier introduction of cow's milk protein and egg powder were also associated with decreased risk for milk and egg allergy, respectively. SUMMARY: Recent studies suggest that early rather than late introduction of allergenic foods reduces the risk of food allergy. The preferred timing of food introduction might be sooner than the current recommendation, and might apply not only to high-risk infants. PMID- 26859366 TI - Recent advances in environmental controls outside the home setting. AB - PURPOSE OF REVIEW: It has been well studied that aeroallergen, mold, and airborne pollutant exposure in the inner-city home environment is associated with significant childhood asthma morbidity. Although the home environment has been extensively studied, the school environment is less well understood. RECENT FINDINGS: In this article, we discuss the relationship between environmental exposures within the school and daycare environment and pediatric asthma morbidity and novel environmental interventions designed to help mitigate pediatric asthma morbidity. SUMMARY: Studies assessing environmental exposures outside the home environment and interventions to mitigate these exposures have the potential to reduce pediatric asthma morbidity. Further study in this area should focus on the complex cost benefit analyses of environmental interventions outside the home setting, while controlling for the home environment. PMID- 26859369 TI - Asthma phenotypes in childhood. AB - PURPOSE OF REVIEW: This review describes the literature over the past 18 months that evaluated childhood asthma phenotypes, highlighting the key aspects of these studies, and comparing these studies to previous ones in this area. RECENT FINDINGS: Recent studies on asthma phenotypes have identified new phenotypes on the basis of statistical analyses (using cluster analysis and latent class analysis methodology) and have evaluated the outcomes and associated risk factors of previously established early childhood asthma phenotypes that are based on asthma onset and patterns of wheezing illness. There have also been investigations focusing on immunologic, physiologic, and genetic correlates of various phenotypes, as well as identification of subphenotypes of severe childhood asthma. SUMMARY: Childhood asthma remains a heterogeneous condition, and investigations into these various presentations, risk factors, and outcomes are important since they can offer therapeutic and prognostic relevance. Further investigation into the immunopathology and genetic basis underlying childhood phenotypes is important so therapy can be tailored accordingly. PMID- 26859370 TI - Inner-city asthma: special considerations for management. AB - PURPOSE OF REVIEW: Asthma is prevalent in inner-city populations, exhibiting significant morbidity and mortality. This review focuses on the consequential findings of recent literature, providing insight into onset of asthma, complicating factors, prediction of exacerbations, and novel treatment strategies. RECENT FINDINGS: Analyses of environmental influence on inner-city children demonstrated novel interactions, implicating potentially protective benefits from early life exposures to pests and pets and isolating detrimental effects of air pollution on asthma morbidity. Through detailed characterization of inner-city asthmatics, predictors of seasonal exacerbations surfaced. Focused, season-specific treatment of inner-city asthmatics with omalizumab identified those most likely to benefit from season-tailored therapy. Comparative studies of urban and rural populations revealed that race and household income, rather than location of residence, impose the greatest risk for increased asthma prevalence and morbidity. SUMMARY: Challenging previously conceived exposure-disease relationships, recent literature has elucidated new avenues in the complex interplay between immunologically active exposures and their effects on inner city asthma. These findings, and improved understanding of other relevant exposures, could steer the direction of primary (and secondary) disease prevention research. Moreover, careful identification of asthma characteristics has effectively established predictors of exacerbations, highlighting individuals for which additional therapies are warranted and for whom such treatments are most likely to be effective. PMID- 26859372 TI - Furthering Medical Education in Texas. AB - Medical education in Texas is moving in the right direction. The Texas Medical Association has been a major partner in advancing medical education initiatives. This special symposium issue on medical education examines residency training costs, the Next Accreditation System, graduate medical education in rural Texas, Texas' physician workforce needs, the current state of education reform, and efforts to retain medical graduates in Texas. PMID- 26859368 TI - Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs. AB - PURPOSE OF REVIEW: Human eosinophils were first identified and named by Paul Ehrlich in 1879 on the basis of the cell's granular uptake of eosin. Although eosinophils represent approximately 1% of peripheral blood leukocytes, they have the propensity to leave the blood stream and migrate into inflamed tissues. Eosinophils and their mediators are critical effectors to asthma and eosinophilic granulomatosis with polyangiitis (EGPA). Eosinophils are equipped with a large number of cell-surface receptors and produce specific cytokines and chemokines. RECENT FINDINGS: Eosinophils are the major source of interleukin-5 and highly express the interleukin-5Ralpha on their surface. Clinical trials evaluating monoclonal antibodies to interleukin-5 (mepolizumab and reslizumab) and its receptor interleukin-5Ralpha (benralizumab) have been or are underway in patients with eosinophilic asthma, EGPA and chronic obstructive pulmonary disease (COPD). Overall, targeting interleukin-5/interleukin-5Ralpha is associated with a marked decrease in blood and sputum eosinophilia, the number of exacerbations and improvement of some clinical parameters in adult patients with severe eosinophilic asthma. Pilot studies suggest that mepolizumab might be a glucocorticoid-sparing treatment in patients with EGPA. A preliminary study found that benralizumab did not reduce the exacerbations and did modify lung function in patients with eosinophilic COPD. SUMMARY: The review examines recent advances in the biology of eosinophils and how targeting the interleukin-5 pathway might offer benefit to some patients with severe asthma, EGPA, and COPD. Interleukin 5/interleukin-5Ralpha-targeted treatments offer promises to patients with eosinophilic respiratory disorders. PMID- 26859374 TI - Experience-Based Lessons From Rural Texas Graduate Medical Education. AB - The University of Texas Medical Branch in Galveston (UTMB) family medicine residency program established a rural training track (RTT) in Weimar, Texas, in 2000. The UTMB-RTT provided a training environment designed specifically to prepare family physicians for rural practice in Texas. From 2000 to 2015, 17 family medicine residents completed their training and graduated from the UTMB RTT. Despite successes with graduate training, rural placement after program completion, and recruitment of underrepresented minorities, the UTMB-RTT closed in June 2015. This paper describes the strengths of and challenges experienced by the program, as well as lessons learned to inform future endeavors. PMID- 26859373 TI - Costs Associated With Residency Training. AB - Texas needs more physicians to care for a rapidly growing population, and new physicians who complete medical training in Texas are likely to remain in the state to practice. The expansion of existing Texas medical schools, along with the development of new schools, has created a need for a corresponding increase in residency and fellowship (graduate medical education, or GME) positions in Texas, and the 2013 and 2015 legislative sessions have funded expanded GME support. While the Centers for Medicare & Medicaid Services pays for the majority of GME positions nationally, those numbers were capped in 1997. Growing populations, particularly in the southern states, have led many institutions- when funds are available--to increase GME positions "over the cap." Texas physicians need to be aware of costs associated with development of accredited GME positions, as well as other measures being taken to support the growth of the physician workforce in the state. PMID- 26859375 TI - The Next Accreditation System. AB - The Accreditation Council for Graduate Medical Education has implemented a new accreditation system for graduate medical education in the United States. This system, called the Next Accreditation System, focuses on more continuous monitoring of the outcomes of residency training, and for high-quality programs, less on the detailed processes of that training. This allows programs to innovate to best meet the needs of their trainees and communities. This new system also reviews the clinical learning environment at each institution sponsoring graduate medical education, focusing on professionalism, trainee supervision, duty hour and fatigue management, care transitions, and integration of residents into patient safety and health care quality. This Next Accreditation System is too new to fully assess its outcomes in better preparing residents for medical practice. Assessments of its early implementation, however, suggest we can expect such outcomes in the near future. PMID- 26859371 TI - Frequent injection cocaine use increases the risk of renal impairment among hepatitis C and HIV coinfected patients. AB - OBJECTIVE: To examine the association between injection cocaine use, hepatitis C virus (HCV) infection, and chronic renal impairment (CRI). DESIGN: Prospective observational cohort study of HIV-HCV coinfected patients. METHODS: Data from 1129 participants in the Canadian Co-Infection Cohort with baseline and follow-up serum creatinine measurements between 2003 and 2014 were analyzed. Prevalent and incident cohorts were created to examine the association between self-reported past, current, and cumulative cocaine use and chronic HCV with CRI. CRI was defined as an estimated glomerular filtration rate below 70 ml/min per 1.73 m. Multivariate logistic regression was used to calculate odds ratios, and discrete time proportional-hazards models were used to calculate hazard ratios for cocaine use, in the two respective cohorts, adjusted for HCV RNA and important demographic, HIV disease stage, and comorbidity confounders. RESULTS: Eighty seven participants (8%) had prevalent CRI. Past injection cocaine use was associated with a two-fold greater risk of prevalent CRI [odds ratio 2.03, 95% confidence interval (CI) 0.96, 4.32]. During follow-up, 126 of 1061 participants (12%) developed incident CRI (31 per 1000 person-years). Compared to nonusers, heavy (>= 3 days/week) and frequent injection cocaine users (>=75% of follow-up time) experienced more rapid progression to CRI (hazard ratio 2.65, 95% CI 1.35, 5.21; and hazard ratio 1.82, 95% CI 1.07, 3.07, respectively). There was no association between chronic HCV and CRI in either cohort. CONCLUSION: After accounting for HCV RNA, frequent and cumulative injection cocaine abuse was associated with CRI progression and should be taken into consideration when evaluating impaired renal function in HIV-HCV coinfection. PMID- 26859376 TI - The Revolution in Medical Education. AB - Medical education has been gradually evolving for hundreds of years, but educators are now seeking to identify ways to prepare students for the future of health care delivery. Medical education reform today focuses on creating entirely new models and is moving away from the traditional, post-Flexnerian organization of the medical school curriculum. Content is now being integrated thematically and presented along interdisciplinary lines with an interdigitation of basic and clinical sciences across all four years. Current trends indicate education should contain elements that produce a physician who is able to improve the quality of health care by taking a humanistic approach to medicine, thinks critically, and participates effectively in multidisciplinary and team approaches to patient care. Ultimately, medical education innovation should recognize the development of a physician is a lifetime process and will approach the formation of physicians from a new paradigm to better serve the educator and prepare the learner for the medical practice of tomorrow. PMID- 26859378 TI - Retaining Medical Graduates in Texas. AB - Texas ranks 43rd in the country in ratio of physicians to patients. Recruiting and encouraging in-migration of physicians, although strengthened by the 2003 liability reforms and streamlining of the licensing process, remain inadequate in keeping up with the state's continuing population growth. Identifying effective mechanisms to retain the young men and women who graduate from medical school in Texas for their graduate medical education (GME) is an important goal. To meet its physician workforce needs, the state must provide adequate opportunities for college graduates to enter medical school, enough GME positions for any medical graduate who chooses to remain in the state for graduate training, and adequate numbers of fellowship programs. PMID- 26859377 TI - The Family Medicine Accelerated Track at Texas Tech University Health Sciences Center. AB - Meeting Texas' future health care needs will be challenging, including the goal for a physician workforce more balanced toward primary care. To help expand the primary care physician workforce, Texas Tech University Health Sciences Center (TTUHSC) School of Medicine developed the Family Medicine Accelerated Track (FMAT), a three-year curriculum that culminates in the MD degree and links medical students to family medicine residency programs at TTUHSC campuses in Lubbock, Amarillo, or the Permian Basin (Odessa and Midland). Twenty current family medicine residents are graduates of the FMAT program, and 30 medical students are enrolled in the program, which is charting a path for curricular innovation in medical education that will be increasingly competency-based. PMID- 26859379 TI - Improving outcomes in community-acquired pneumonia. AB - PURPOSE OF REVIEW: Community-acquired pneumonia (CAP) is a pervasive disease that is encountered in outpatient and inpatient settings. CAP is the leading cause of death from an infectious disease and accounts for significant worldwide morbidity and mortality. This update reviews current advances that can be used to promote improved outcomes in CAP. RECENT FINDINGS: Early recognition of CAP and its severe presentations, with appropriate site of care decisions, leads to reduced patient mortality. In addition to traditional prognostic tools, certain serum biomarkers can assist in defining disease severity and guide treatment and management strategies. The use of macrolides as part of combination antibiotic therapy has shown beneficial mortality effects across the CAP disease spectrum, especially for those with severe illness. When treating community-associated, methicillin-resistant Staphylococcus aureus pneumonia, use of an antitoxin antibiotic is likely to be valuable. Adjunctive therapy with corticosteroids may prevent delayed clinical resolution in selected patients with severe CAP. Recent data expand on the interaction of CAP with comorbid disease, particularly cardiovascular disease, and its impact on mortality in CAP patients. SUMMARY: Improved diagnostic tools, optimized treatment regimens, and enhanced understanding of CAP-induced perturbations in comorbid disease states hold promise to improve patient outcomes. PMID- 26859381 TI - Effect of Plyometric Training on Handspring Vault Performance and Functional Power in Youth Female Gymnasts. AB - This study aimed to determine the effect of plyometric training (PT) when added to habitual gymnastic training (HT) on handspring vault (HV) performance variables. Twenty youth female competitive gymnasts (Age: 12.5 +/- 1.67 y) volunteered to participate and were randomly assigned to two independent groups. The experimental plyometric training group (PTG) undertook a six-week plyometric program, involving two additional 45 min PT sessions a week, alongside their HT, while the control group (CG) performed regular HT only. Videography was used (120 Hz) in the sagittal plane to record both groups performing three HVs for both the baseline and post-intervention trials. Furthermore, participants completed a countermovement jump test (CMJ) to assess the effect of PT on functional power. Through the use of Quintic biomechanics software, significant improvements (P < 0.05) were found for the PTG for run-up velocity, take-off velocity, hurdle to board distance, board contact time, table contact time and post-flight time and CMJ height. However, there were no significant improvements on pre-flight time, shoulder angle or hip angle on the vault for the PTG. The CG demonstrated no improvement for all HV measures. A sport-specific PT intervention improved handspring vault performance measures and functional power when added to the habitual training of youth female gymnasts. The additional two hours plyometric training seemingly improved the power generating capacity of movement-specific musculature, which consequently improved aspects of vaulting performance. Future research is required to examine the whether the improvements are as a consequence of the additional volume of sprinting and jumping activities, as a result of the specific PT method or a combination of these factors. PMID- 26859380 TI - Isotope effect analyses provide evidence for an altered transition state for RNA 2'-O-transphosphorylation catalyzed by Zn(2+). AB - Solvent D2O and (18)O kinetic isotope effects on RNA 2'-O-transphosphorylation catalyzed by Zn(2+) demonstrate an altered transition state relative to specific base catalysis. A recent model from DFT calculations involving inner sphere coordination to the non-bridging and leaving group oxygens is consistent with the data. PMID- 26859383 TI - Correction: GLD-4-Mediated Translational Activation Regulates the Size of the Proliferative Germ Cell Pool in the Adult C. elegans Germ Line. PMID- 26859384 TI - Correction: Using Highlighting to Train Attentional Expertise. PMID- 26859385 TI - A Glance at Recombination Hotspots in the Domestic Cat. AB - Recombination has essential roles in increasing genetic variability within a population and in ensuring successful meiotic events. The objective of this study is to (i) infer the population-scaled recombination rate (rho), and (ii) identify and characterize regions of increased recombination rate for the domestic cat, Felis silvestris catus. SNPs (n = 701) were genotyped in twenty-two East Asian feral cats (random bred). The SNPs covered ten different chromosomal regions (A1, A2, B3, C2, D1, D2, D4, E2, F2, X) with an average region size of 850 Kb and an average SNP density of 70 SNPs/region. The Bayesian method in the program inferRho was used to infer regional population recombination rates and hotspots localities. The regions exhibited variable population recombination rates and four decisive recombination hotspots were identified on cat chromosome A2, D1, and E2 regions. As a description of the identified hotspots, no correlation was detected between the GC content and the locality of recombination spots, and the hotspots enclosed L2 LINE elements and MIR and tRNA-Lys SINE elements. PMID- 26859387 TI - Multiple emissive triarylborane-A2H2 and triarylborane-Zn-A2H2 porphyrin conjugates. AB - Triarylborane-A2H2 (1) and triarylborane-Zn-A2H2 porphyrins (2) have been synthesized by acid catalyzed condensation of 4-dimesitylboryl-benzaldehyde and dipyrromethane under ambient conditions. Compounds 1 and 2 showed multiple emission bands upon excitation at the triarylborane dominated absorption region (350 nm). Detailed experimental and computational studies show that the multiple emission features of 1 and 2 arise as a result of a partial energy transfer from the donor (triarylborane) to the acceptor (porphyrin) moieties. Compounds 1 and 2 showed very high selectivities towards fluoride ions compared to other competing anions. PMID- 26859386 TI - Characterization of Behavioral, Neuropathological, Brain Metabolic and Key Molecular Changes in zQ175 Knock-In Mouse Model of Huntington's Disease. AB - Huntington's disease (HD) is caused by an expansion of the trinucleotide poly (CAG) tract located in exon 1 of the huntingtin (Htt) gene leading to progressive neurodegeneration in selected brain regions, and associated functional impairments in motor, cognitive, and psychiatric domains. Since the discovery of the gene mutation that causes the disease, mouse models have been developed by different strategies. Recently, a new model, the zQ175 knock-in (KI) line, was developed in an attempt to have the Htt gene in a context and causing a phenotype that more closely mimics HD in humans. The behavioral phenotype was characterized across the independent laboratories and important features reminiscent of human HD are observed in zQ175 mice. In the current study, we characterized the zQ175 model housed in an academic laboratory under reversed dark-light cycle, including motor function, in vivo longitudinal structural MRI imaging for brain volume, MRS for striatal metabolites, neuropathology, as well as a panel of key disease marker proteins in the striatum at different ages. Our results suggest that homozygous zQ175 mice exhibited significant brain atrophy before the motor deficits and brain metabolite changes. Altered striatal medium spiny neuronal marker, postsynaptic marker protein and complement component C1qC also characterized zQ175 mice. Our results confirmed that the zQ175 KI model is valuable in understanding of HD-like pathophysiology and evaluation of potential therapeutics. Our data also provide suggestions to select appropriate outcome measurements in preclinical studies using the zQ175 mice. PMID- 26859388 TI - Exploring the Mechanisms of a Patient-Centred Assessment with a Solution Focused Approach (DIALOG+) in the Community Treatment of Patients with Psychosis: A Process Evaluation within a Cluster-Randomised Controlled Trial. AB - BACKGROUND: DIALOG+ is a new intervention to make routine community mental health meetings therapeutically effective. It involves a structured assessment of patient concerns and a solution-focused approach to address them. In a randomised controlled trial, DIALOG+ was associated with better subjective quality of life and other outcomes in patients with psychosis, but it was not clear how this was achieved. This study explored the possible mechanisms. METHODS: This was a mixed methods process evaluation within a cluster-randomised controlled trial. Focus groups and interviews were conducted with patients and clinicians who experienced DIALOG+ and were analysed using thematic analysis. The content of DIALOG+ sessions was recorded and analysed according to (i) the type of actions agreed during sessions and (ii) the domains discussed. The subjective quality of life measure was analysed with mixed-effects models to explore whether the effect of DIALOG+ was limited to life domains that had been addressed in sessions or consistent across all domains. RESULTS: Four qualitative themes emerged regarding the mechanisms of DIALOG+: (1) a comprehensive structure; (2) self-reflection; (3) therapeutic self-expression; and (4) empowerment. Patients took responsibility for the majority of actions agreed during sessions (65%). The treatment effect on subjective quality of life was largest for living situation (accommodation and people that the patient lives with) and mental health. Two of these domains were among the three most commonly discussed in DIALOG+ sessions (accommodation, mental health, and physical health). CONCLUSION: DIALOG+ initiates positive, domain-specific change in the areas that are addressed in sessions. It provides a comprehensive and solution-focused structure to routine meetings, encourages self-reflection and expression, and empowers patients. Future research should strengthen and monitor these factors. TRIAL REGISTRATION: ISRCTN Registry ISRCTN34757603. PMID- 26859389 TI - Highly Accurate Structure-Based Prediction of HIV-1 Coreceptor Usage Suggests Intermolecular Interactions Driving Tropism. AB - HIV-1 entry into host cells is mediated by interactions between the V3-loop of viral glycoprotein gp120 and chemokine receptor CCR5 or CXCR4, collectively known as HIV-1 coreceptors. Accurate genotypic prediction of coreceptor usage is of significant clinical interest and determination of the factors driving tropism has been the focus of extensive study. We have developed a method based on nonlinear support vector machines to elucidate the interacting residue pairs driving coreceptor usage and provide highly accurate coreceptor usage predictions. Our models utilize centroid-centroid interaction energies from computationally derived structures of the V3-loop:coreceptor complexes as primary features, while additional features based on established rules regarding V3-loop sequences are also investigated. We tested our method on 2455 V3-loop sequences of various lengths and subtypes, and produce a median area under the receiver operator curve of 0.977 based on 500 runs of 10-fold cross validation. Our study is the first to elucidate a small set of specific interacting residue pairs between the V3-loop and coreceptors capable of predicting coreceptor usage with high accuracy across major HIV-1 subtypes. The developed method has been implemented as a web tool named CRUSH, CoReceptor USage prediction for HIV-1, which is available at http://ares.tamu.edu/CRUSH/. PMID- 26859392 TI - Special Issue: Microfluidic Lab-on-a-Chip Platforms for High-Performance Diagnostics. AB - The field of microfluidics has seen breath-taking progress since its beginnings in the 1980s and early 1990s. While much of the initial work was a by-product of mainstream micro-electro-mechanical systems (MEMS) and silicon based fabrication schemes, soon a specialized research field developed. Over the last decade a strong, highly interdisciplinary microfluidics community emerged with roots in classical silicon microfabrication as well as chemistry, physics, biotechnology, medicine and various engineering disciplines. [...]. PMID- 26859390 TI - The Efficacy of Hyperbaric Oxygen Therapy on Middle Cerebral Artery Occlusion in Animal Studies: A Meta-Analysis. AB - BACKGROUND: Inconsistent results have been reported for hyperbaric oxygen therapy (HBO) for acute stroke. We conducted a systematic review and meta-analysis to evaluate the benefit of HBO in animal studies of middle cerebral artery occlusion (MCAO). METHODS: A systematic search of the literature published prior to September 2015 was performed using Embase, Medline (OvidSP), Web of Science and PubMed. Keywords included "hyperoxia" OR "hyperbaric oxygen" OR "HBO" AND "isch(a)emia" OR "focal cerebral ischemia" OR "stroke" OR "infarct" OR "middle cerebral artery occlusion (MCAO)." The primary endpoints were the infarct size and/or neurological outcome score evaluated after HBO treatment in MCAO. Heterogeneity was analyzed using Cochrane Library's RevMan 5.3.5. RESULTS: Fifty one studies that met the inclusion criteria were identified among the 1198 studies examined. When compared with control group data, HBO therapy resulted in infarct size reduction or improved neurological function (32% decrease in infarct size; 95% confidence interval (CI), range 28%-37%; p < 0.00001). Mortality was 18.4% in the HBO group and 26.7% in the control group (RR 0.72, 95% CI, 0.54 0.98; p = 0.03). Subgroup analysis showed that a maximal neuro-protective effect was reached when HBO was administered immediately after MCAO with an absolute atmospheric pressure (ATA) of 2.0 (50% decrease; 95% CI, 43% -57% decrease; p < 0.0001) and more than 6 hours HBO treatment (53% decrease; 95% CI, 41% -64% decrease; p = 0.0005). CONCLUSIONS: HBO had a neuro-protective effect and improved survival in animal models of MCAO, especially in animals given more than 6 hours of HBO and when given immediately after MCAO with 2.0 ATA. PMID- 26859391 TI - Cortical Mechanisms of Central Fatigue and Sense of Effort. AB - The purpose of this study was to investigate cortical mechanisms upstream to the corticospinal motor neuron that may be associated with central fatigue and sense of effort during and after a fatigue task. We used two different isometric finger abduction protocols to examine the effects of muscle activation and fatigue the right first dorsal interosseous (FDI) of 12 participants. One protocol was intended to assess the effects of muscle activation with minimal fatigue (control) and the other was intended to elicit central fatigue (fatigue). We hypothesized that high frequency repetitive transcranial magnetic stimulation (rTMS) of the supplementary motor area (SMA) would hasten recovery from central fatigue and offset a fatigue-induced increase in sense of effort by facilitating the primary motor cortex (M1). Constant force-sensation contractions were used to assess sense of effort associated with muscle contraction. Paired-pulse TMS was used to assess intracortical inhibition (ICI) and facilitation (ICF) in the active M1 and interhemispheric inhibitory (IHI) was assessed to determine if compensation occurs via the resting M1. These measures were made during and after the muscle contraction protocols. Corticospinal excitability progressively declined with fatigue in the active hemisphere. ICF increased at task failure and ICI was also reduced at task failure with no changes in IHI found. Although fatigue is associated with progressive reductions in corticospinal excitability, compensatory changes in inhibition and facilitation may act within, but not between hemispheres of the M1. rTMS of the SMA following fatigue enhanced recovery of maximal voluntary force and higher levels of ICF were associated with lower sense of effort following stimulation. rTMS of the SMA may have reduced the amount of upstream drive required to maintain motor output, thus contributing to a lower sense of effort and increased rate of recovery of maximal force. PMID- 26859393 TI - Intra-/Interobserver Agreement of Enhancement Pattern for Pancreatic Head Lesions Using Contrast-Enhanced Ultrasound: According to EFSUMB Guidelines. AB - OBJECTIVE: To evaluate the intra-/interobserver agreement of the visual interpretation of contrast-enhanced ultrasound (CEUS) of pancreatic head lesions and its concordance with the histological test results. MATERIAL AND METHODS: Two observers (A + B) evaluated by simple visual interpretation 40 consecutive CEUS examinations of pancreatic head lesions and one of the observers evaluated the examinations twice (A1 + A2). The examinations were evaluated according to the criteria outlined in EFSUMB guidelines. The two experienced observers were blinded to histological evidence and clinical information of tumor type and to each other's results. RESULTS: The kappa value for the intraobserver evaluation between observer A1 and A2 was 0.89, equating to almost perfect agreement. The kappa value for the interobserver evaluation between observer A1 and B was 0.76 and between observer A2 and B it was 0.75, both equating to substantial agreement. Evaluation of the visual interpretation compared to the histological test result showed a positive predictive value for A1, A2 and B versus biopsy of 97%, 94% and 90% respectively and an accuracy of 83%, 88% and 73% respectively. CONCLUSIONS: Visual interpretation for assessment of contrast enhancement of pancreatic head lesions seemed to be an accurate method with reproducible results and good concordance with the histological test results. PMID- 26859394 TI - The Combination of In vivo (124)I-PET and CT Small Animal Imaging for Evaluation of Thyroid Physiology and Dosimetry. AB - OBJECTIVE: A thyroid rat model combining functional and anatomical information would be of great benefit for better modeling of thyroid physiology and for absorbed dose calculations. Our aim was to show that (124)I-PET and CT small animal imaging are useful as a combined model for studying thyroid physiology and dose calculation. METHODS: Seven rats were subjects for multiple thyroid (124)I imaging and CT-scans. S-values [mGy/MBqs] for different thyroid sizes were simulated. A phantom with spheres was designed for validation of performances of the small animal PET and CT imaging systems. RESULTS: Small animal image-based measurements of the activity amount and the volumes of the spheres with a priori known volumes showed a good agreement with their corresponding actual volumes. The CT scans of the rats showed thyroid volumes from 34-70 mL. CONCLUSIONS: The wide span in volumes of thyroid glands indicates the importance of using an accurate volume-measuring technique such as the small animal CT. The small animal PET system was on the other hand able to accurately estimate the activity concentration in the thyroid volumes. We conclude that the combination of the PET and CT image information is essential for quantitative thyroid imaging and accurate thyroid absorbed dose calculation. PMID- 26859396 TI - Improving Accuracy for Image Fusion in Abdominal Ultrasonography. AB - Image fusion involving real-time ultrasound (US) is a technique where previously recorded computed tomography (CT) or magnetic resonance images (MRI) are reformatted in a projection to fit the real-time US images after an initial co registration. The co-registration aligns the images by means of common planes or points. We evaluated the accuracy of the alignment when varying parameters as patient position, respiratory phase and distance from the co-registration points/planes. We performed a total of 80 co-registrations and obtained the highest accuracy when the respiratory phase for the co-registration procedure was the same as when the CT or MRI was obtained. Furthermore, choosing co registration points/planes close to the area of interest also improved the accuracy. With all settings optimized a mean error of 3.2 mm was obtained. We conclude that image fusion involving real-time US is an accurate method for abdominal examinations and that the accuracy is influenced by various adjustable factors that should be kept in mind. PMID- 26859395 TI - Comparison of 1-Ethyl-3-(3-Dimethylaminopropyl) Carbodiimide Based Strategies to Crosslink Antibodies on Amine-Functionalized Platforms for Immunodiagnostic Applications. AB - 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) alone, and in combination with N-hydroxysuccinimide (NHS) or sulfoNHS were employed for crosslinking anti human fetuin A (HFA) antibodies on 3-aminopropyltriethoxysilane (APTES) functionalized surface plasmon resonance (SPR) gold chip and 96-well microtiter plate. The SPR immunoassay and sandwich enzyme linked immunosorbent immunoassay (ELISA) for HFA clearly demonstrated that EDC crosslinks anti-HFA antibodies to APTES-functionalized bioanalytical platforms more efficiently than EDC/NHS and EDC/sulfoNHS at a normal pH of 7.4. Similar results were obtained by sandwich ELISAs for human Lipocalin-2 and human albumin, and direct ELISA for horseradish peroxidase. The more efficient crosslinking of antibodies by EDC to the APTES functionalized platforms increased the cost-effectiveness and analytical performance of our immunoassays. This study will be of wide interest to researchers developing immunoassays on APTES-functionalized platforms that are being widely used in biomedical diagnostics, biosensors, lab-on-a-chip and point of-care-devices. It stresses a critical need of an intensive investigation into the mechanisms of EDC-based amine-carboxyl coupling under various experimental conditions. PMID- 26859397 TI - Importance of Attenuation Correction (AC) for Small Animal PET Imaging. AB - The purpose of this study was to investigate whether a correction for annihilation photon attenuation in small objects such as mice is necessary. The attenuation recovery for specific organs and subcutaneous tumors was investigated. A comparison between different attenuation correction methods was performed. METHODS: Ten NMRI nude mice with subcutaneous implantation of human breast cancer cells (MCF-7) were scanned consecutively in small animal PET and CT scanners (MicroPET(TM) Focus 120 and ImTek's MicroCAT(TM) II). CT-based AC, PET based AC and uniform AC methods were compared. RESULTS: The activity concentration in the same organ with and without AC revealed an overall attenuation recovery of 9-21% for MAP reconstructed images, i.e., SUV without AC could underestimate the true activity at this level. For subcutaneous tumors, the attenuation was 13 +/- 4% (9-17%), for kidneys 20 +/- 1% (19-21%), and for bladder 18 +/- 3% (15-21%). The FBP reconstructed images showed almost the same attenuation levels as the MAP reconstructed images for all organs. CONCLUSIONS: The annihilation photons are suffering attenuation even in small subjects. Both PET-based and CT-based are adequate as AC methods. The amplitude of the AC recovery could be overestimated using the uniform map. Therefore, application of a global attenuation factor on PET data might not be accurate for attenuation correction. PMID- 26859398 TI - Visual Suppression is Impaired in Spinocerebellar Ataxia Type 6 but Preserved in Benign Paroxysmal Positional Vertigo. AB - Positional vertigo is a common neurologic emergency and mostly the etiology is peripheral. However, central diseases may mimic peripheral positional vertigo at their initial presentation. We here describe the results of a visual suppression test in six patients with spinocerebellar ataxia type 6 (SCA6), a central positional vertigo, and nine patients with benign paroxysmal positional vertigo (BPPV), the major peripheral positional vertigo. As a result, the visual suppression value of both diseases differed significantly; e.g., 22.5% in SCA6 and 64.3% in BPPV (p < 0.001). There was a positive correlation between the visual suppression value and disease duration, cerebellar atrophy, and CAG repeat length of SCA6 but they were not statistically significant. In conclusion, the present study showed for the first time that visual suppression is impaired in SCA6, a central positional vertigo, but preserved in BPPV, the major peripheral positional vertigo, by directly comparing both groups. The abnormality in the SCA6 group presumably reflects dysfunction in the central visual fixation pathway at the cerebellar flocculus and nodulus. This simple test might aid differential diagnosis of peripheral and central positional vertigo at the earlier stage of disease. PMID- 26859399 TI - Prenatal Diagnosis of Chromosome Abnormalities: A 13-Year Institution Experience. AB - OBJECTIVE: To analyze trends in screening and invasive prenatal diagnosis of chromosome abnormalities (CA) over a 13-year period and correlate them to changes in the national prenatal screening policy. METHODS: We retrospectively reviewed Down syndrome (DS) screening tests and fetal karyotypes obtained by prenatal invasive testing (IT) in our fetal medicine unit between January 1999 and December 2011. RESULTS: A total of 24,226 prenatal screening tests for DS and 11,045 invasive procedures have been analyzed. Over a 13-year period, utilization of non-invasive screening methods has significantly increased from 57% to 89%. The percentage of invasive procedures has declined from 49% to 12%, although the percentage of IT performed for maternal anxiety has increased from 22% to 55%. The percentage of detected CA increased from 2.5% to 5.9%. Overall, 31 invasive procedures are needed to diagnose 1 abnormal case, being 23 procedures in medical indications and 241 procedures in non-medical indications. CONCLUSIONS: Our experience on screening and invasive prenatal diagnostic practice shows a decrease of the number of IT, with a parallel decline in medical indications. There is an increasing efficiency of prenatal screening program to detect CA. Despite the increasing screening policies, our population shows a growing request for prenatal IT. The a priori low risk population shows a not negligible residual risk for relevant CA. This observation challenges the current prenatal screening strategy focused on DS; showing that the residual risk is higher than the current cut-off used to indicate an invasive technique. PMID- 26859400 TI - Gold Nanoparticles-Coated SU-8 for Sensitive Fluorescence-Based Detections of DNA. AB - SU-8 epoxy-based negative photoresist has been extensively employed as a structural material for fabrication of numerous biological microelectro mechanical systems (Bio-MEMS) or lab-on-a-chip (LOC) devices. However, SU-8 has a high autofluorescence level that limits sensitivity of microdevices that use fluorescence as the predominant detection workhorse. Here, we show that deposition of a thin gold nanoparticles layer onto the SU-8 surface significantly reduces the autofluorescence of the coated SU-8 surface by as much as 81% compared to bare SU-8. Furthermore, DNA probes can easily be immobilized on the Au surface with high thermal stability. These improvements enabled sensitive DNA detection by simple DNA hybridization down to 1 nM (a two orders of magnitude improvement) or by solid-phase PCR with sub-picomolar sensitivity. The approach is simple and easy to perform, making it suitable for various Bio-MEMs and LOC devices that use SU-8 as a structural material. PMID- 26859402 TI - Detection of Dissolved Lactose Employing an Optofluidic Micro-System. AB - In this work, a novel optofluidic sensor principle is employed for a non-invasive and label-free characterization of lactose containing liquid samples. Especially for medicine and food industry, a simple, fast and accurate determination of the amount of lactose in various products is highly desirable. The presented system exploits the impact of dissolved molecules on the refractive index for sample characterization. On the optofluidic chip, a microfluidic channel filled with the analyte is hit by slightly diverging laser light. The center incident angle of the beam on-chip is set close to the critical angle for total internal reflection. Both the reflected and the transmitted light signals are recorded at the solid-liquid interface. The ratio of those two signals is then used as representative value for the analyte. Using this principle, lactose containing samples were differentiated based on their concentrations at a step size of 10 mmol/L. The use of the signals ratio instead of a single signal approach improves the stability of the system significantly, allowing for higher resolutions to be achieved. Furthermore, the fabrication of the devices in PDMS ensures biocompatibility and provides low absorbance of light in the visible range. PMID- 26859401 TI - Cell-Based Biosensors: Electrical Sensing in Microfluidic Devices. AB - Cell-based biosensors provide new horizons for medical diagnostics by adopting complex recognition elements such as mammalian cells in microfluidic devices that are simple, cost efficient and disposable. This combination renders possible a new range of applications in the fields of diagnostics and personalized medicine. The review looks at the most recent developments in cell-based biosensing microfluidic systems with electrical and electrochemical transduction, and relevance to medical diagnostics. PMID- 26859403 TI - Identification of Medicare Recipients at Highest Risk for Clostridium difficile Infection in the US by Population Attributable Risk Analysis. AB - BACKGROUND: Population attributable risk percent (PAR%) is an epidemiological tool that provides an estimate of the percent reduction in total disease burden if that disease could be entirely eliminated among a subpopulation. As such, PAR% is used to efficiently target prevention interventions. Due to significant limitations in current Clostridium difficile Infection (CDI) prevention practices and the development of new approaches to prevent CDI, such as vaccination, we determined the PAR% for CDI in various subpopulations in the Medicare 5% random sample. METHODS: This was a retrospective cohort study using the 2009 Medicare 5% random sample. Comorbidities, infections, and healthcare exposures during the 12 months prior to CDI were identified. CDI incidence and PAR% were calculated for each condition/exposure. Easy to identify subpopulations that could be targeted from prevention interventions were identified based on PAR%. FINDINGS: There were 1,465,927 Medicare beneficiaries with 9,401 CDI cases for an incidence of 677/100,000 persons. Subpopulations representing less than 15% of the entire population and with a PAR% >= 30% were identified. These included deficiency anemia (PAR% = 37.9%), congestive heart failure (PAR% = 30.2%), fluid and electrolyte disorders (PAR% = 29.6%), urinary tract infections (PAR% = 40.5%), pneumonia (PAR% = 35.2%), emergent hospitalization (PAR% = 48.5%) and invasive procedures (PAR% = 38.9%). Stratification by age and hospital exposures indicates hospital exposures are more strongly associated with CDI than age. SIGNIFICANCE: Small and identifiable subpopulations that account for relatively large proportions of CDI cases in the elderly were identified. These data can be used to target specific subpopulations for CDI prevention interventions. PMID- 26859404 TI - A Theoretical Model for the Associative Nature of Conference Participation. AB - Participation in conferences is an important part of every scientific career. Conferences provide an opportunity for a fast dissemination of latest results, discussion and exchange of ideas, and broadening of scientists' collaboration network. The decision to participate in a conference depends on several factors like the location, cost, popularity of keynote speakers, and the scientist's association with the community. Here we discuss and formulate the problem of discovering how a scientist's previous participation affects her/his future participations in the same conference series. We develop a stochastic model to examine scientists' participation patterns in conferences and compare our model with data from six conferences across various scientific fields and communities. Our model shows that the probability for a scientist to participate in a given conference series strongly depends on the balance between the number of participations and non-participations during his/her early connections with the community. An active participation in a conference series strengthens the scientist's association with that particular conference community and thus increases the probability of future participations. PMID- 26859405 TI - Dual Energy Spectral CT Imaging for Colorectal Cancer Grading: A Preliminary Study. AB - OBJECTIVES: To assess the diagnostic value of dual energy spectral CT imaging for colorectal cancer grading using the quantitative iodine density measurements in both arterial phase (AP) and venous phase (VP). METHODS: 81 colorectal cancer patients were divided into two groups based on their pathological findings: a low grade group including well (n = 13) and moderately differentiated cancer (n = 24), and a high grade group including poorly differentiated (n = 42) and signet ring cell cancer (n = 2). Iodine density (ID) in the lesions was derived from the iodine-based material decomposition (MD) image and normalized to that in the psoas muscle to obtain normalized iodine density (NID). The difference in ID and NID between AP and VP was calculated. RESULTS: The ID and NID values of the low grade cancer group were, 14.65 +/- 3.38 mg/mL and 1.70 +/- 0.33 in AP, and 21.90 +/- 3.11 mg/mL and 2.05 +/- 0.32 in VP, respectively. The ID and NID values for the high grade cancer group were 20.63 +/- 3.72 mg/mL and 2.95 +/- 0.72 in AP, and 26.27 +/- 3.10mg/mL and 3.51 +/- 1.12 in VP, respectively. There was significant difference for ID and NID between the low grade and high grade cancer groups in both AP and VP (all p<0.001). ROC analysis indicated that NID of 1.92 in AP provided 70.3% sensitivity and 97.7% specificity in differentiating low grade cancer from high grade cancer. CONCLUSIONS: The quantitative measurement of iodine density in AP and VP can provide useful information to differentiate low grade colorectal cancer from high grade colorectal cancer with NID in AP providing the greatest diagnostic value. PMID- 26859406 TI - Community Evolution in International Migration Top1 Networks. AB - Focusing on each country's topmost destination/origin migration relation with other countries, this study builds top1 destination networks and top1 origin networks in order to understand their skeletal construction and community dynamics. Each top1 network covers approximately 50% of the complete migrant network stock for each decade between 1960 and 2000. We investigate the community structure by implementing the Girvan-Newman algorithm and compare the number of components and communities to illustrate their differences. We find that (i) both top1 networks (origin and destination) exhibited communities with a clear structure and a surprising evolution, although 80% edges persist between each decade; (ii) top1 destination networks focused on developed countries exhibiting shorter paths and preferring more advance countries, while top1 origin networks focused both on developed as well as more substantial developing nations that presented a longer path and more stable groups; (iii) only few countries have a decisive influence on community evolution of both top1 networks. USA took the leading position as a destination country in top1 destination networks, while China and India were the main Asian emigration countries in top1 origin networks; European countries and the Russian Federation played an important role in both. PMID- 26859407 TI - Cytoprotective and Antioxidant Effects of an Edible Herb, Enhydra fluctuans Lour. (Asteraceae), against Experimentally Induced Lead Acetate Intoxication. AB - BACKGROUND: Enhydra fluctuans Lour. (Asteraceae), an edible aquatic herb, is traditionally employed against toxic effects of heavy metals in India. The present study was planned to discover the protective effect of edible extract of E. fluctuans (AEEF) against Pb toxicity. METHODS: The cytoprotective role of AEEF was determined on murine hepatocytes employing MTT assay and Hoechst staining. The effects on lipid peroxidation, protein carbonylation, endogenous redox systems and the transcription levels of apoptotic proteins were studied after incubating the hepatocytes with AEEF (400 MUg/ml) + Pb-acetate (6.8 MUM). The defensive role of AEEF (100 mg/kg) against Pb-acetate (5 mg/kg) intoxication was measured in mice by in vivo assays. Biochemical, haematological and histological parameters, intracellular Pb burden and redox status were measured. RESULTS: AEEF exhibited a concentration dependent cytoprotective effect against Pb-induced cytotoxicity in vitro. Pb-acetate incubation significantly (p < 0.01) altered the extents of ROS production ?, protein carbonylation ?, lipid peroxidation ?, endogenous antioxidant enzymes ? and GSH ? in vitro. Besides, Pb-acetate significantly (p < 0.01) induced apoptosis in the hepatocytes apparent from the altered expressions of apoptotic proteins viz. Apaf-1 ?, Bad ?, Bcl-2 ?, Cyt C ?, cleaved caspases?, Bid ? and Fas ?. However, AEEF (400 MUg/ml) could significantly (p < 0.05-0.01) attenuate the Pb-acetate mediated toxic manifestation in vitro. In in vivo assay, Pb-acetate (5 mg/kg) treated mice exhibited significantly (p < 0.01) high intracellular Pb content. A high Pb burden within the tissues caused significant (p < 0.05-0.01) patho-physiological alterations viz. ROS production ?, protein carbonylation?, lipid peroxidation ?, DNA fragmentation ?, ATP formation ?, mitochondrial co-enzymes Q ?, endogenous antioxidant enzymes ? and GSH ? within the selected tissues. The haematological and serum biochemical parameters were significantly (p < 0.05-0.01) different in the Pb-acetate treated mice. Finally, histological assessment imposed significant toxic occurrence within the organs of Pb-intoxicated animals. However, concurrent administration of AEEF (100 mg/kg) could significantly (p < 0.05-0.01) reinstate the Pb-acetate mediated toxicity. CONCLUSION: Presence of metal chelators and phyto-antioxidants within AEEF would offer overall protection through promoting Pb clearance coupled with restoring redox balance. PMID- 26859409 TI - Continuity of care and 30-day readmission for patients evaluated in the emergency room after cerebral aneurysm treatment. AB - BACKGROUND: The association between continuity of care and the rate of 30-day readmissions after surgical procedures continues to be debated. OBJECTIVE: To investigate the association of 30-day readmissions with evaluation in the hospital where the original procedure was performed for patients presenting to the emergency department (ED) after cerebral aneurysm treatment. METHODS: We performed a cohort study of patients with cerebral aneurysms, who were evaluated in the ED within 30 days after discharge following surgical clipping or endovascular coiling between 2009 and 2013, and were registered in the Statewide Planning and Research Cooperative System database. A propensity score adjusted model was used to control for confounding, whereas mixed effects accounted for clustering at the hospital level. RESULTS: Of the 452 patients presenting to the ED, 218 (48.2%) were evaluated in a different hospital from that in which the original procedure was performed (7.7% readmitted), and 234 (51.8%) were evaluated at the original hospital (18.4% readmitted). In a multivariable analysis, we showed that evaluation in the ED of the original hospital was associated with decreased rate of 30-day readmission (OR=0.41; 95% CI 0.22 to 0.78). We found similar associations in a mixed-effects logistic regression model (OR=0.46; 95% CI 0.35 to 0.84) and a propensity score adjusted model (OR=0.41; 95% CI 0.22 to 0.77). This corresponds to10 patients needing to be evaluated in the hospital at which the original procedure was performed to prevent one readmission. CONCLUSIONS: Using a comprehensive all-payer cohort of patients in New York State, who were evaluated in the ED after cerebral aneurysm treatment, we identified an association between assessment in the hospital at which the original procedure was performed and a lower rate of 30-day readmissions. This underlines the potential importance of continuity of care for surgical patients to prevent readmission. PMID- 26859410 TI - Dynamics of nasopharyngeal pneumococcal carriage during the course of viral bronchiolitis. AB - The effect of viral infection on nasopharyngeal carriage of Streptococcus pneumoniae during childhood is not well known. We studied dynamics of pneumococcal colonization by quantitative PCR during the natural course of viral bronchiolitis. At time of admission, 47 (47%) of 100 patients with bronchiolitis carried pneumococci. In patients with viral bronchiolitis who did not receive antibiotics, pneumococcal load decreased from time of admission to discharge (n = 35, cycle threshold 23 vs. 25, P = 0.0017) and from discharge to follow-up (n = 22, cycle threshold 25 vs. 40, P = 0.003). We conclude that viral respiratory infection is negatively associated with pneumococcal colonization of the upper airways. Pediatr Pulmonol. 2016;51:863-867. (c) 2016 Wiley Periodicals, Inc. PMID- 26859408 TI - Absence of Tumor-Infiltrating Lymphocyte Is a Reproducible Predictive Factor for Sentinel Lymph Node Metastasis: A Multicenter Database Study by the Brazilian Melanoma Group. AB - AIMS: The aim of this study is to confirm the function of tumor-infiltrating lymphocytes (TILs) in sentinel lymph node (SLN) metastasis. MATERIALS AND METHODS: This retrospective study included 633 patients with invasive melanoma who underwent sentinel lymph node biopsy in 7 referral centers certified by the Brazilian Melanoma Group. Independent risk factors of sentinel node metastasis (SNL) were identified by multiple logistic regression. RESULTS: SLN metastasis was detected in 101 of 633 cases (16.1%) and in 93 of 428 patients (21.7%) when melanomas <= 1mm were excluded. By multiple logistic regression, the absence of TILs was as an independent risk factor of SLN metastasis (OR = 1.8; 95%CI: 1.1 3.0), in addition to Breslow index (greater than 2.00 mm), lymph vascular invasion, and presence of mitosis. CONCLUSION: SLNB can identify patients who might benefit from immunotherapy, and the determination of predictors of SLNB positivity can help select the proper population for this type of therapy. The absence of TILs is a reproducible parameter that can predict SLNB positivity in melanoma patients, since this study was made with several centers with different dermatopathologists. PMID- 26859412 TI - Directly linked hydroporphyrin dimers. AB - Directly linked hydroporphyrin (chlorin) dimers were accessed regioselectively from bromochlorins. Versatile 15-borylated chlorins were prepared in excellent yield via Miyaura borylation. Suzuki coupling yielded meso-meso-linked homo- and heterodimers, and meso-beta-linked dimers. The photophysical and electrochemical properties of the dimers are reported. PMID- 26859413 TI - Prolonged Medical Therapy Increases the Risk of Surgical Complications in Patients with Severe Ulcerative Colitis. AB - AIMS: To determine the risk factors of surgical complications and the optimal timing of surgery for patients with severe ulcerative colitis (UC). METHODS: One hundred one UC patients who had undergone surgery for a severe indication were retrospectively reviewed. Indications included severe disease unresponsive to medical therapy, massive bleeding, toxic megacolon, and colon perforation. Outcomes were compared based on the occurrence or absence of surgical complications. Patients with severe disease unresponsive to medical therapy were investigated separately to determine the optimal timing of surgery. RESULTS: There was no significant difference regarding the use of rescue therapy. The duration of all medical therapy for a severe attack was the only significant factor associated with a surgical complication (p = 0.032). In patients with severe disease unresponsive to medical therapy, the receiver operating characteristic curve analysis showed that 30.5 days was the length of medical therapy after which the risk of surgical complications significantly increased. CONCLUSIONS: In patients with severe UC, rescue therapy itself was not related to an increased risk of surgical complications. However, prolonged medical therapy increased the risk of surgical complications. Patients should undergo surgery within 30 days from the institution of medical therapy for a severe attack. PMID- 26859411 TI - Forecasting influenza outbreak dynamics in Melbourne from Internet search query surveillance data. AB - BACKGROUND: Accurate forecasting of seasonal influenza epidemics is of great concern to healthcare providers in temperate climates, as these epidemics vary substantially in their size, timing and duration from year to year, making it a challenge to deliver timely and proportionate responses. Previous studies have shown that Bayesian estimation techniques can accurately predict when an influenza epidemic will peak many weeks in advance, using existing surveillance data, but these methods must be tailored both to the target population and to the surveillance system. OBJECTIVES: Our aim was to evaluate whether forecasts of similar accuracy could be obtained for metropolitan Melbourne (Australia). METHODS: We used the bootstrap particle filter and a mechanistic infection model to generate epidemic forecasts for metropolitan Melbourne (Australia) from weekly Internet search query surveillance data reported by Google Flu Trends for 2006 14. RESULTS AND CONCLUSIONS: Optimal observation models were selected from hundreds of candidates using a novel approach that treats forecasts akin to receiver operating characteristic (ROC) curves. We show that the timing of the epidemic peak can be accurately predicted 4-6 weeks in advance, but that the magnitude of the epidemic peak and the overall burden are much harder to predict. We then discuss how the infection and observation models and the filtering process may be refined to improve forecast robustness, thereby improving the utility of these methods for healthcare decision support. PMID- 26859415 TI - Very Low Birth Weight Monochorionic Diamniotic Twins as a Risk Factor for Symptomatic Patent Ductus Arteriosus. AB - BACKGROUND: Some prior studies have shown that symptomatic patent ductus arteriosus (sPDA) is highly familial. Although it is estimated that both genetic and environmental factors may contribute to sPDA, evidence is still lacking. OBJECTIVE: The aim of this study was to determine the risk factors for sPDA, focusing on the genetic and in utero environment by analyzing very low birth weight (VLBW) singletons and twins. METHODS: This retrospective case-control study reviewed the medical records of 445 VLBW infants (25 weeks <= gestational age <32 weeks, 600 g <= birth weight <1,500 g) and compared the incidence of sPDA among monochorionic diamniotic (MD) twins (n = 65), dichorionic diamniotic (DD) twins (n = 66), and singletons (n = 314). RESULTS: Stepwise multiple regression analysis showed that twin siblings (p = 0.001), gestational week (p < 0.001), antenatal steroid use (p = 0.021), and premature rupture of membranes (p = 0.002) were independent predictors of sPDA. Incidence of sPDA in MD twin siblings was significantly higher than that in singletons (p < 0.01), whereas no significant difference was found between singletons and DD twins or between MD and DD twins. CONCLUSIONS: The current results show that being a VLBW MD twin is an independent risk factor for sPDA, and that both genetic and in utero environmental factors may contribute to its development. PMID- 26859414 TI - Inverse Relationship between Progesterone Receptor and Myc in Endometrial Cancer. AB - Endometrial cancer, the most common gynecologic malignancy, is a hormonally regulated disease. Response to progestin therapy positively correlates with hormone receptor expression, in particular progesterone receptor (PR). However, many advanced tumors lose PR expression. We recently reported that the efficacy of progestin therapy can be significantly enhanced by combining progestin with epigenetic modulators, which we term "molecularly enhanced progestin therapy." What remained unclear was the mechanism of action and if estrogen receptor alpha (ERalpha), the principle inducer of PR, is necessary to restore functional expression of PR via molecularly enhanced progestin therapy. Therefore, we modeled advanced endometrial tumors that have lost both ERalpha and PR expression by generating ERalpha-null endometrial cancer cell lines. CRISPR-Cas9 technology was used to delete ERalpha at the genomic level. Our data demonstrate that treatment with a histone deacetylase inhibitor (HDACi) was sufficient to restore functional PR expression, even in cells devoid of ERalpha. Our studies also revealed that HDACi treatment results in marked downregulation of the oncogene Myc. We established that PR is a negative transcriptional regulator of Myc in endometrial cancer in the presence or absence of ERalpha, which is in contrast to studies in breast cancer cells. First, estrogen stimulation augmented PR expression and decreased Myc in endometrial cancer cell lines. Second, progesterone increased PR activity yet blunted Myc mRNA and protein expression. Finally, overexpression of PR by adenoviral transduction in ERalpha-null endometrial cancer cells significantly decreased expression of Myc and Myc regulated genes. Analysis of the Cancer Genome Atlas (TCGA) database of endometrial tumors identified an inverse correlation between PR and Myc mRNA levels, with a corresponding inverse correlation between PR and Myc downstream transcriptional targets SRD5A1, CDK2 and CCNB1. Together, these data reveal a previously unanticipated inverse relationship between the tumor suppressor PR and the oncogene Myc in endometrial cancer. PMID- 26859417 TI - One size may not fit all when it comes to growth references for preterm infants. PMID- 26859418 TI - Islamic American doctors and premature babies. PMID- 26859419 TI - Oestradiol, amenorrhoea and lipids in adolescent girls with eating disorders: do they affect long-term cardiovascular risk? PMID- 26859420 TI - Oxygen saturation profile of term equivalent extreme preterm infants at discharge - comparison with healthy term counterparts. AB - AIM: Compare the oxygen saturation profiles before discharge of neonates born extremely preterm (<28 weeks), now at term equivalent age, with healthy term neonates and assess the impact of feeding on this profile in each group. METHODS: We prospectively evaluated and compared the oxygen saturation profile in 15 very low birthweight infants at term equivalent age, ready to be discharged home without any oxygen and 15 term newborns after 48 hours of life. We also evaluated and compared the saturations of these two groups during a one-hour period during and after feeding. RESULTS: Term equivalent preterm and term infants spent median 3% and 0%, respectively, of the time below 90% in a 12-hour saturation-recording period. Term infants spent a median 0.26% and 0.65% of the time in <90% saturation during feed time and no feed time, respectively. In contrast, preterm infants spent significantly more time <90% saturation (3.47% and 3.5% during feed time and no feed time, respectively). CONCLUSION: Term equivalent preterm infants spent significantly more time in a saturation range <90% compared to term infants. Feeding had little effect on saturation profile overall within each group. PMID- 26859421 TI - Is tasting innate? PMID- 26859422 TI - Establishment of a xenograft model to explore the mechanism of bone destruction by human oral cancers and its application to analysis of role of RANKL. AB - BACKGROUND: The molecular mechanism underlying bone invasion caused by oral squamous cell carcinoma (OSCC) is not well understood. To elucidate the molecular mechanism, the development of more suitable xenograft models mimicking human mandibular bone destruction by OSCC has been required. MATERIALS AND METHODS: Human OSCC cell lines, HSC3, HSC3-C1, and HSC3-R2, were injected in the periosteal region of the mandible in athymic mice, and the bone destruction was analyzed. Receptor activators of nuclear factor kappa-B ligand (RANKL) mRNA and protein expression levels were measured in the OSCC cell lines. Antibody that specifically neutralizes mouse RANKL and human RANKL, respectively, was injected into HSC3-cell-transplanted mice. RESULTS: Transplantation of HSC3 cells induced mandibular bone destruction. Histological examination revealed numerous osteoclasts on the bone destruction surface. Fibroblastic cell intervention between the cancer nests and resorbing bone surface was observed in a similar fashion to those observed in human OSCC cases. The number of osteoclasts and fibroblasts was significantly correlated. Bone destruction induced by the transplantation of HSC3 cells was reduced by injection of an antibody that specifically neutralizes mouse RANKL. Transplantation of HSC3-R2 cells, which overexpresses RANKL, induced advanced bone destruction compared to that of HSC3 C1 cells, which only overexpress the empty vector. CONCLUSIONS: We established a useful xenograft model for investigating the molecular mechanism underlying the bone destruction induced by OSCC in the jaw. This model will be used to investigate the precise roles of several cytokines synthesized by both cancer cells and fibroblastic cells in OSCC-associated bone destruction in the jaw. PMID- 26859423 TI - Effects of Ziram on Rat and Human 11beta-Hydroxysteroid Dehydrogenase Isoforms. AB - Ziram is a widely used fungicide for crops. Its endocrine disrupting action is largely unknown. 11beta-Hydroxysteroid dehydrogenases, isoforms 1 (HSD11B1) and 2 (HSD11B2), have been demonstrated to be the regulators of the local levels of active glucocorticoids, which have broad physiological actions. In the present study, the potency of ziram was tested for its inhibition of rat and human HSD11B1 and HSD11B2. Ziram showed the inhibition of rat HSD11B1 reductase with IC50 of 87.07 MUM but no inhibition of human enzyme at 100 MUM. Ziram showed the inhibition of both rat and human HSD11B2 with IC50 of 90.26 and 34.93 MUM, respectively. Ziram exerted competitive inhibition of rat HSD11B1 when 11 dehydrocorticosterone was used and mixed inhibition when NADPH was supplied. Ziram exerted a noncompetitive inhibition of both rat and human HSD11B2 when steroid substrates were used and an uncompetitive inhibition when NAD(+) was supplied. Increased DTT concentrations antagonized rat and human HSD11B2 activities, suggesting that the cysteine residues are associated with the inhibition of ziram. In conclusion, for humans, ziram is a selective inhibitor of HSD11B2, implying that this agent may cause excessive glucocorticoid action in local tissues such as the kidney, brain, and placenta. PMID- 26859424 TI - Under-Appreciated Steps in Instrument Development, Part I: Starting With Validity. PMID- 26859425 TI - Evaluation of the position of unerupted mandibular third molars with and without root dilacerations: a study on panoramic radiographs. AB - BACKGROUND: Factors that can directly influence the extraction of third molars include the position of the tooth and the presence of root dilacerations. Knowledge of these features favors an accurate therapeutic evaluation of third molars; therefore, the aim of this study was to evaluate, using panoramic radiographs, the positioning of unerupted third molars with and without root dilacerations and to verify a possible association between these two variables. METHODS: In this study, 16,136 panoramic radiographs were analyzed, including 1756 lower third molars, in which the positioning was assessed according to the Winter classification and the presence of root dilacerations was determined. The data obtained from the assessments of the frequencies of the positions and the presence of root dilacerations of impacted mandibular third molar was described. A chi2 test was applied to verify a possible association between the variables. RESULTS: The results indicated that the most frequent position was mesioangular (44.5%), followed by horizontal (24.9%), vertical (17.4%), distoangular (12.5%), inverted (0.4%), and linguoangular (0.3%). Of the mandibular third molars evaluated, 35% had root dilacerations. The chi-square test revealed a significant association between the position of the tooth and the presence of root dilacerations (P<0.0001, chi2=34.28). The frequency of root dilaceration was statistically higher for the vertical (45.5%) and distoangular positions (40.9%). CONCLUSIONS: The mesioangular position was the most prevalent location for lower third molars, and the highest frequencies of root dilacerations were observed in the vertical and distoangular positions. Knowledge about the prevalence of root dilacerations and the significant association between the position of the third molars and root dilacerations will allow safer surgical planning for dental extractions of third molars. PMID- 26859426 TI - Effects of acute aerobic exercise on leukocyte inflammatory gene expression in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is an autoimmune disease with a persistent systemic inflammation. Exercise induced inflammatory response in SLE remains to be fully elucidated. The aim of this study was to assess the effects of acuteexercise on leukocyte gene expression in active (SLEACTIVE) and inactive SLE (SLEINACTIVE) patients and healthy controls(HC). METHODS: All subjects (n = 4 per group) performed a 30-min single bout of acute aerobic exercise (~70% of VO2peak) on a treadmill, and blood samples were collected for RNA extraction from circulating leukocyte at baseline, at the end of exercise, and after three hours of recovery. The expression of a panel of immune-related genes was evaluated by a quantitative PCR array assay. Moreover, network-based analyses were performed to interpret transcriptional changes occurring after the exercise challenge. RESULTS: In all groups, a single bout of acute exercise led to the down regulation of the gene expression of innate and adaptive immunity at the end of exercise (e.g., TLR3, IFNG, GATA3, FOXP3, STAT4) with a subsequent up-regulation occurring upon recovery. Exercise regulated the expression of inflammatory genes in the blood leukocytes of the SLE patients and HC, although the SLE groups exhibited fewer modulated genes and less densely connected networks (number of nodes: 29, 40 and 58; number of edges: 29, 60 and 195; network density: 0.07, 0.08 and 0.12, for SLEACTIVE, SLEINACTIVE and HC, respectively). CONCLUSION: The leukocytes from the SLE patients, irrespective of disease activity, showed a down regulated inflammatory geneexpression immediately after acute aerobic exercise, followed by an up-regulation at recovery. Furthermore, less organized gene networks were observed in the SLE patients, suggesting that they may be deficient in triggering a normal exercised-induced immune transcriptional response. PMID- 26859428 TI - Broadband ultrasonic spectroscopy for the characterization of viscoelastic materials. AB - In this study, non-destructive experimental method based on acoustic through transmission technique along with broadband spectroscopy is proposed in order to determine the linear viscoelastic material properties in 20-400 kHz range. Material properties such as phase velocity and attenuation coefficient of longitudinal and shear waves are measured. Diffraction correction developed for focused transducers is used to eliminate the spreading error due to the spherical wave generated by the hydrophone which is used as a transmitter. Method is validated on polymethyl methacrylate (PMMA). Both longitudinal wave velocity, shear wave velocity and attenuation coefficient of longitudinal wave of PMMA are in agreement with the previously reported values which are given in the literature. Attenuation coefficient of shear wave in PMMA is measured successfully and in agreement with the theoretical predictions. Longitudinal wave velocity and corresponding attenuation coefficient of gelatine gel are also measured. PMID- 26859427 TI - Wide Range pH-Tolerable Silicon@Pyrite Cobalt Dichalcogenide Microwire Array Photoelectrodes for Solar Hydrogen Evolution. AB - This study employed silicon@cobalt dichalcogenide microwires (MWs) as wide range pH-tolerable photocathode material for solar water splitting. Silicon microwire arrays were fabricated through lithography and dry etching technologies. Si@Co(OH)2 MWs were utilized as precursors to synthesize Si@CoX2 (X = S or Se) photocathodes. Si@CoS2 and Si@CoSe2 MWs were subsequently prepared by thermal sulfidation and hydrothermal selenization reaction of Si@Co(OH)2, respectively. The CoX2 outer shell served as cocatalyst to accelerate the kinetics of photogenerated electrons from the underlying Si MWs and reduce the recombination. Moreover, the CoX2 layer completely deposited on the Si surface functioned as a passivation layer by decreasing the oxide formation on Si MWs during solar hydrogen evolution. Si@CoS2 photocathode showed a photocurrent density of -3.22 mA cm(-2) at 0 V (vs RHE) in 0.5 M sulfuric acid electrolyte, and Si@CoSe2 MWs revealed moderate photocurrent density of -2.55 mA cm(-2). However, Si@CoSe2 presented high charge transfer efficiency in neutral and alkaline electrolytes. Continuous chronoamperometry in acid, neutral, and alkaline solutions was conducted at 0 V (vs RHE) to evaluate the photoelectrochemical durability of Si@CoX2 MWs. Si@CoS2 electrode showed no photoresponse after the chronoamperometry test because it was etched through the electrolyte. By contrast, the photocurrent density of Si@CoSe2 MWs gradually increased to -5 mA cm(-2) after chronoamperometry characterization owing to the amorphous structure generation. PMID- 26859429 TI - Photoswitching Near-Infrared Fluorescence from Polymer Nanoparticles Catapults Signals over the Region of Noises and Interferences for Enhanced Sensitivity. AB - As a very sensitive technique, photoswitchable fluorescence not only gains ultrasensitivity but also imparts many novel and unexpected applications. Applications of near-infrared (NIR) fluorescence have demonstrated low background noises, high tissue-penetrating ability, and an ability to reduce photodamage to live cells. Because of these desired features, NIR-fluorescent dyes have been the premium among fluorescent dyes, and probes with photoswitchable NIR fluorescence are even more desirable for enhanced signal quality in the emerging optical imaging modalities but rarely used because they are extremely challenging to design and construct. Using a spiropyran derivative functioning as both a photoswitch and a fluorophore to launch its periodically modulated red fluorescence excitation energy into a NIR acceptor, we fabricated core-shell polymer nanoparticles exhibiting a photoswitchable fluorescence signal within the biological window (~700-1000 nm) with a peak maximum of 776 nm. Live cells constantly synthesize new molecules, including fluorescent molecules, and also endocytose exogenous particles, including fluorescent particles. Upon excitation at different wavelengths, these fluorescent species bring about background noises and interferences covering nearly the whole visible region and therefore render many intracellular targets unaddressable. The oscillating NIR fluorescence signal with an on/off ratio of up to 67 that the polymer nanoparticles display is beyond the typical background noises and interferences, thus producing superior sharpness, reliability, and signal-to-noise ratios in cellular imaging. Taking these salient features, we anticipate that these types of nanoparticles will be useful for in vivo imaging of biological tissue and other complex specimens, where two-photon activation and excitation are used in combination with NIR fluorescence photoswitching. PMID- 26859430 TI - Electrochemical biosensor modified with dsDNA monolayer for restriction enzyme activity determination. AB - A simple and cost effective method for the determination of restriction endonuclease activity is presented. dsDNA immobilized at a gold electrode surface is used as the enzymatic substrate, and an external cationic redox probe is employed in voltammetric measurements for analytical signal generation. The assessment of enzyme activity is based on a decrease of a current signal derived from reduction of methylene blue which is present in the sample solution. For this reason, the covalent attachment of the label molecule is not required which significantly reduces costs of the analysis and simplifies the entire determination procedure. The influence of buffer components on utilized dsDNA/MCH monolayer stability and integrity is also verified. Electrochemical impedance spectroscopy measurements reveal that due to pinhole formation during enzyme activity measurement the presence of any surfactants should be avoided. Additionally, it is shown that the sensitivity of the electrochemical biosensor can be tuned by changing the restriction site location along the DNA length. Under optimal conditions the proposed biosensor exhibits a linear response toward PvuII activity within a range from 0.25 to 1.50 U/MUL. PMID- 26859431 TI - A novel ultrasonic NDE for shrink fit welded structures using interface waves. AB - Reactor vessel inspection is a critical part of safety maintenance in a nuclear power plant. The inspection of shrink fit welded structures in a reactor nozzle can be a challenging task due to the complicated geometry. Nozzle inspection using pseudo interface waves allows us to inspect the nozzle from outside of the nuclear reactor. In this study, layered concentric pipes were manufactured with perfect shrink fit conditions using stainless steel 316. The displacement distributions were calculated with boundary conditions for a shrink fit welded structure. A multi-transducer guided wave phased array system was employed to monitor the welding quality of the nozzle end at a distance from a fixed position. The complicated geometry of a shrink fit welded structure can be overcome by using the pseudo interface waves in identifying the location and size of defects. The experimental results demonstrate the feasibility of detecting weld delamination and defects. PMID- 26859432 TI - Ribozyme Catalysis with a Twist: Active State of the Twister Ribozyme in Solution Predicted from Molecular Simulation. AB - We present results from molecular dynamics simulations and free energy calculations of the twister ribozyme at different stages along the reaction path to gain insight into its mechanism. The results, together with recent biochemical experiments, provide support for a mechanism involving general-acid catalysis by a conserved adenine residue in the active site. Although adenine has been previously implicated as a general acid acting through the N1 position in other ribozymes such as the hairpin and VS ribozymes, in the twister ribozyme there may be a twist. Biochemical experiments suggest that general acid catalysis may occur through the N3 position, which has never before been implicated in this role; however, currently, there is a lack of a detailed structural model for the active state of the twister ribozyme in solution that is consistent with these and other experiments. Simulations in a crystalline environment reported here are consistent with X-ray crystallographic data, and suggest that crystal packing contacts trap the RNA in an inactive conformation with U-1 in an extruded state that is incompatible with an in-line attack to the scissile phosphate. Simulations in solution, on the other hand, reveal this region to be dynamic and able to adopt a conformation where U-1 is stacked with G33. In this state, the nucleophile is in line with the scissile phosphate, and the N1 position of G33 and N3 position of A1 are poised to act as a general base and acid, respectively, as supported by mutational experiments. Free energy calculations further predict the electrostatic environment causes a shift of the microscopic pKa at the N3 position of A1 toward neutrality by approximately 5 pKa units. These results offer a unified interpretation of a broad range of currently available experimental data that points to a novel mode of general acid catalysis through the N3 position of an adenine nucleobase, thus expanding the repertoire of known mechanistic strategies employed by small nucleolytic ribozymes. PMID- 26859433 TI - Effect of phenolic compounds from spices consumed in China on heterocyclic amine profiles in roast beef patties by UPLC-MS/MS and multivariate analysis. AB - Ultra performance liquid chromatography-tandem mass spectrometry and multivariate analysis were used to exploit the effect and further synergistic or antagonistic interactions of main phenolic compounds with the same ratios as in spices consumed in China, on the profiles of HAs in roast beef patties. Quantitative levels of harman (1-methyl-9H-pyrido[3,4-b]indole), norharman (9H-pyrido[3,4 b]indole), PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), DMIP (2-amino 1,6-dimethylimidazo[4,5-b]pyridine), 1,5,6-TMIP (2-amino-1,5,6 trimethylimidazo[4,5-b]pyridine), MeIQx (2-amino-3,8-dimethylimidazo[4,5 f]quinoxaline) and 4,8-DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline) were detected in all of the beef patties. The formation of most of these seven HAs was significantly (P<0.05) enhanced by phenolic compounds. Mixed and corresponding single phenolic compounds had different effects on HA profiles. DMIP, 1,5,6-TMIP and 4,8-DiMeIQx were investigated as differentiating factors for single compounds, while harman and MeIQx for mixed ones. Moreover, certain combination of phenolic compounds have synergistic on harman, norharman and MeIQx, but antagonistic effects on the formation of DMIP and 4,8-DiMeIQx. The results may shed light on the mechanism for the effects of spices on the formation of HAs. PMID- 26859435 TI - Near-Infrared Light Activation of Proteins Inside Living Cells Enabled by Carbon Nanotube-Mediated Intracellular Delivery. AB - Light-responsive proteins have been delivered into the cells for controlling intracellular events with high spatial and temporal resolution. However, the choice of wavelength is limited to the UV and visible range; activation of proteins inside the cells using near-infrared (NIR) light, which has better tissue penetration and biocompatibility, remains elusive. Here, we report the development of a single-walled carbon nanotube (SWCNT)-based bifunctional system that enables protein intracellular delivery, followed by NIR activation of the delivered proteins inside the cells. Proteins of interest are conjugated onto SWCNTs via a streptavidin-desthiobiotin (SA-DTB) linkage, where the protein activity is blocked. SWCNTs serve as both a nanocarrier for carrying proteins into the cells and subsequently a NIR sensitizer to photothermally cleave the linkage and release the proteins. The released proteins become active and exert their functions inside the cells. We demonstrated this strategy by intracellular delivery and NIR-triggered nuclear translocation of enhanced green fluorescent protein, and by intracellular delivery and NIR-activation of a therapeutic protein, saporin, in living cells. Furthermore, we showed that proteins conjugated onto SWCNTs via the SA-DTB linkage could be delivered to the tumors, and optically released and activated by using NIR light in living mice. PMID- 26859434 TI - Surfactant Lipids at the Host-Environment Interface. Metabolic Sensors, Suppressors, and Effectors of Inflammatory Lung Disease. AB - The lipid composition of pulmonary surfactant is unlike that of any other body fluid. This extracellular lipid reservoir is also uniquely susceptible by virtue of its direct and continuous exposure to environmental oxidants, inflammatory agents, and pathogens. Historically, the greatest attention has been focused on those biophysical features of surfactant that serve to reduce surface tension at the air-liquid interface. More recently, surfactant lipids have also been recognized as bioactive molecules that maintain immune quiescence in the lung but can also be remodeled by the inhaled environment into neolipids that mediate key roles in inflammation, immunity, and fibrosis. This review focuses on the roles in inflammatory and infectious lung disease of two classes of native surfactant lipids, glycerophospholipids and sterols, and their corresponding oxidized species, oxidized glycerophospholipids and oxysterols. We highlight evidence that surfactant composition is sensitive to circulating lipoproteins and that the lipid milieu of the alveolus should thus be recognized as susceptible to diet and common systemic metabolic disorders. We also discuss intriguing evidence suggesting that oxidized surfactant lipids may represent an evolutionary link between immunity and tissue homeostasis that arose in the primordial lung. Taken together, the emerging picture is one in which the unique environmental susceptibility of the lung, together with its unique extracellular lipid requirements, may have made this organ both an evolutionary hub and an engine for lipid-immune cross-talk. PMID- 26859436 TI - Power and the association with relationship quality in South African couples: Implications for HIV/AIDS interventions. AB - INTRODUCTION: Power imbalances within sexual relationships have significant implications for HIV prevention in sub-Saharan Africa. Little is known about how power influences the quality of a relationship, which could be an important pathway leading to healthy behavior around HIV/AIDS. METHODS: This paper uses data from 448 heterosexual couples (896 individuals) in rural KwaZulu-Natal, South Africa who completed baseline surveys from 2012 to 2014 as part of a couples-based HIV intervention trial. Using an actor-partner interdependence perspective, we assessed: (1) how both partners' perceptions of power influences their own (i.e., actor effect) and their partner's reports of relationship quality (i.e., partner effect); and (2) whether these associations differed by gender. We examined three constructs related to power (female power, male equitable gender norms, and shared power) and four domains of relationship quality (intimacy, trust, mutually constructive communication, and conflict). RESULTS: For actor effects, shared power was strongly and consistently associated with higher relationship quality across all four domains. The effect of shared power on trust, mutually constructive communication, and conflict were stronger for men than women. The findings for female power and male equitable gender norms were more mixed. Female power was positively associated with women's reports of trust and mutually constructive communication, but negatively associated with intimacy. Male equitable gender norms were positively associated with men's reports of mutually constructive communication. For partner effects, male equitable gender norms were positively associated with women's reports of intimacy and negatively associated with women's reports of conflict. CONCLUSIONS: Research and health interventions aiming to improving HIV-related behaviors should consider sources of shared power within couples and potential leverage points for empowerment at the couple level. Efforts solely focused on empowering women should also take the dyadic environment and men's perspectives into account to ensure positive relationship outcomes. PMID- 26859438 TI - Air Pollution and Pulmonary Tuberculosis: A Nested Case-Control Study among Members of a Northern California Health Plan. AB - BACKGROUND: Ecologic analyses, case-case comparisons, and animal experiments suggest positive associations between air pollution and tuberculosis. OBJECTIVES: We evaluated this hypothesis in a large sample, which yielded results that are applicable to the general population. METHODS: We conducted a case-control study nested within a cohort of Kaiser Permanente of Northern California members. All active pulmonary tuberculosis (TB) cases newly diagnosed between 1996 and 2010 (n = 2,309) were matched to two controls (n = 4,604) by age, sex, and race/ethnicity on the index date corresponding with the case diagnosis date. Average individual level concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter with aerodynamic diameter <= 2.5 MUm (PM2.5) and 10 MUm (PM10) for 2 years before diagnosis/entry into the study were estimated using measurements from the California Air Resources Board monitor closest to the participant's residence. RESULTS: In single-pollutant adjusted conditional logistic regression models, the pulmonary TB odds ratios (95% confidence intervals) for the highest quintile (vs. lowest) were 1.50 (95% CI: 1.15, 1.95) for CO and 1.42 (95% CI: 1.10, 1.84) for NO2. Corresponding estimates were higher among never [1.68 (95% CI: 1.26, 2.24)] than ever [1.19 (95% CI: 0.74, 1.92)] smokers for CO. In contrast, for NO2, estimates were higher among ever [1.81 (95% CI: 1.13, 2.91)] than never [1.29 (95% CI: 0.97, 1.71)] smokers. O3 was inversely associated for smokers [0.66 (95% CI: 0.43, 1.02)] and never smokers [0.65 (95% CI: 0.52, 0.81)]. No other consistent patterns were observed. CONCLUSIONS: In this first, to our knowledge, U.S. nested case-control study on air pollution and pulmonary TB, we observed positive associations with ambient CO and NO2, which require confirmation. CITATION: Smith GS, Van Den Eeden SK, Garcia C, Shan J, Baxter R, Herring AH, Richardson DB, Van Rie A, Emch M, Gammon MD. 2016. Air pollution and pulmonary tuberculosis: a nested case-control study among members of a Northern California health plan. Environ Health Perspect 124:761-768; http://dx.doi.org/10.1289/ehp.1408166. PMID- 26859439 TI - Initial Series of Four-Arm Robotic Completely Intracorporeal Ileal Ureter. AB - Ileal ureter formation has been found to be a suitable treatment option for long, chronic ureteral strictures not amendable to less invasive forms of repair. Minimally invasive surgical techniques for this condition have been investigated. We report the first series of robotic completely intracorporeal ileal ureter using a four-arm robotic technique. Three patients underwent this procedure, including one patient with a solitary kidney. All procedures were performed effectively with a median operative time of 450 minutes (range: 420-540) and median estimated blood loss of 100 mL (range: 50-200). Postoperatively, one patient suffered volvulus and subsequent necrosis of small bowel and ileal ureter, which required re-operation and small bowel resection, including the ileal ureter. The other two patients report no surgical complications to date. This early series represents preliminary technical procedure feasibility. Further experience is necessary. PMID- 26859440 TI - [What Surgeons Should Know about Risk Management]. AB - Background: The fact that medical treatment is associated with errors has long been recognized. Based on the principle of "first do no harm", numerous efforts have since been made to prevent such errors or limit their impact. However, recent statistics show that these measures do not sufficiently prevent grave mistakes with serious consequences. Preventable mistakes such as wrong patient or wrong site surgery still frequently occur in error statistics. Methods: Based on insight from research on human error, in due consideration of recent legislative regulations in Germany, the authors give an overview of the clinical risk management tools needed to identify risks in surgery, analyse their causes, and determine adequate measures to manage those risks depending on their relevance. The use and limitations of critical incident reporting systems (CIRS), safety checklists and crisis resource management (CRM) are highlighted. Also the rationale for IT systems to support the risk management process is addressed. Results/Conclusion: No single tool of risk management can be effective as a standalone instrument, but unfolds its effect only when embedded in a superordinate risk management system, which integrates tailor-made elements to increase patient safety into the workflows of each organisation. Competence in choosing adequate tools, effective IT systems to support the risk management process as well as leadership and commitment to constructive handling of human error are crucial components to establish a safety culture in surgery. PMID- 26859442 TI - Fluorescence Products from Terrylenediimide with Singlet Oxygen: Red, Green, and Near-Infrared Emission. AB - The rich photo-oxidation pathways and products of terrylenediimide (TDI) with singlet oxygen ((1)O2) have been examined by powerful computational approaches. Potential energy profiles and product fluorescence properties are characterized. A variety of new products are unraveled and predicted to emit fluorescence at both visible and near-infrared ranges, which could open the possibility for interesting applications of using TDI as a fluorescence probe for the single molecule detection of (1)O2 and designing multicolor photoconvertible fluorophores based on (1)O2 oxidation. PMID- 26859437 TI - Biochemical Methods To Investigate lncRNA and the Influence of lncRNA:Protein Complexes on Chromatin. AB - Long noncoding RNAs (lncRNAs), defined as nontranslated transcripts greater than 200 nucleotides in length, are often differentially expressed throughout developmental stages, tissue types, and disease states. The identification, visualization, and suppression/overexpression of these sequences have revealed impacts on a wide range of biological processes, including epigenetic regulation. Biochemical investigations on select systems have revealed striking insight into the biological roles of lncRNAs and lncRNA:protein complexes, which in turn prompt even more unanswered questions. To begin, multiple protein- and RNA centric technologies have been employed to isolate lncRNA:protein and lncRNA:chromatin complexes. LncRNA interactions with the multi-subunit protein complex PRC2, which acts as a transcriptional silencer, represent some of the few cases where the binding affinity, selectivity, and activity of a lncRNA:protein complex have been investigated. At the same time, recent reports of full-length lncRNA secondary structures suggest the formation of complex structures with multiple independent folding domains and pave the way for more detailed structural investigations and predictions of lncRNA three-dimensional structure. This review will provide an overview of the methods and progress made to date as well as highlight new methods that promise to further inform the molecular recognition, specificity, and function of lncRNAs. PMID- 26859443 TI - Resident-Led Palliative Care Education Project. AB - BACKGROUND AND OBJECTIVE: Despite the growth of palliative medicine, 39% of hospitals do not have palliative care teams for consultation or to provide resident education. We examined the impact of resident-led education in palliative care principles on attitudes toward and comfort with palliative medicine and end-of-life care among internal medicine residents. METHODS: An educational module designed by the authors was presented to other internal medicine residents in the program. Pre- and post-intervention survey data measuring residents' agreement with various statements regarding palliative medicine and end-of-life care were analyzed. Residents' agreement with various statements regarding palliative medicine and end-of-life care on a 5-point Likert scale was analyzed. RESULTS: Following the intervention, participants reported improved comfort with general knowledge of palliative medicine (p < 0.01), specific resources available to patients (p < 0.001), and explaining the difference between palliative care and end-of-life care (p < 0.001). In each of the seven specific domains of palliative medicine covered in the educational session, residents reported a statistically significant increase in comfort in all of the areas addressed (p < 0.05). CONCLUSION: This study demonstrates that a resident-led curriculum in palliative medicine can improve resident comfort within this still-under-represented area of medicine. PMID- 26859444 TI - The genetic classification of prostate cancer: what's on the horizon? PMID- 26859445 TI - Atomoxetine: A Review of Its Pharmacokinetics and Pharmacogenomics Relative to Drug Disposition. AB - Atomoxetine is a selective norepinephrine (NE) reuptake inhibitor approved for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children (>=6 years of age), adolescents, and adults. Its metabolism and disposition are fairly complex, and primarily governed by cytochrome P450 (CYP) 2D6 (CYP2D6), whose protein expression varies substantially from person to person, and by race and ethnicity because of genetic polymorphism. These differences can be substantial, resulting in 8-10-fold differences in atomoxetine exposure between CYP2D6 poor metabolizers and extensive metabolizers. In this review, we have attempted to revisit and analyze all published clinical pharmacokinetic data on atomoxetine inclusive of public access documents from the new drug application submitted to the United States Food and Drug Administration (FDA). The present review focuses on atomoxetine metabolism, disposition, and genetic polymorphisms of CYP2D6 as they specifically relate to atomoxetine, and provides an in-depth discussion of the fundamental pharmacokinetics of the drug including its absorption, distribution, metabolism, and excretion in pediatric and adult populations. Further, a summary of relationships between genetic variants of CYP2D6 and to some degree, CYP2C19, are provided with respect to atomoxetine plasma concentrations, central nervous system (CNS) pharmacokinetics, and associated clinical implications for pharmacotherapy. Lastly, dosage adjustments based on pharmacokinetic principles are discussed. PMID- 26859447 TI - Mouse EEG spike detection based on the adapted continuous wavelet transform. AB - OBJECTIVE: Electroencephalography (EEG) is an important tool in the diagnosis of epilepsy. Interictal spikes on EEG are used to monitor the development of epilepsy and the effects of drug therapy. EEG recordings are generally long and the data voluminous. Thus developing a sensitive and reliable automated algorithm for analyzing EEG data is necessary. APPROACH: A new algorithm for detecting and classifying interictal spikes in mouse EEG recordings is proposed, based on the adapted continuous wavelet transform (CWT). The construction of the adapted mother wavelet is founded on a template obtained from a sample comprising the first few minutes of an EEG data set. MAIN RESULT: The algorithm was tested with EEG data from a mouse model of epilepsy and experimental results showed that the algorithm could distinguish EEG spikes from other transient waveforms with a high degree of sensitivity and specificity. SIGNIFICANCE: Differing from existing approaches, the proposed approach combines wavelet denoising, to isolate transient signals, with adapted CWT-based template matching, to detect true interictal spikes. Using the adapted wavelet constructed from a predefined template, the adapted CWT is calculated on small EEG segments to fit dynamical changes in the EEG recording. PMID- 26859446 TI - Preclinical Experimental and Mathematical Approaches for Assessing Effective Doses of Inhaled Drugs, Using Mometasone to Support Human Dose Predictions. AB - BACKGROUND: Understanding the relationship between dose, lung exposure, and drug efficacy continues to be a challenging aspect of inhaled drug development. An experimental inhalation platform was developed using mometasone furoate to link rodent lung exposure to its in vivo pharmacodynamic (PD) effects. METHODS: We assessed the effect of mometasone delivered directly to the lung in two different rodent PD models of lung inflammation. The data obtained were used to develop and evaluate a mathematical model to estimate drug dissolution, transport, distribution, and efficacy, following inhaled delivery in rodents and humans. RESULTS: Mometasone directly delivered to the lung, in both LPS and Alternaria alternata rat models, resulted in dose dependent inhibition of BALf cellular inflammation. The parameters for our mathematical model were calibrated to describe the observed lung and systemic exposure profiles of mometasone in humans and in animal models. We found that physicochemical properties, such as lung fluid solubility and lipophilicity, strongly influenced compound distribution and lung retention. CONCLUSIONS: Presently, we report on a novel and sophisticated mathematical model leading to improvements in a current inhaled drug development practices by providing a quantitative understanding of the relationship between PD effects and drug concentration in lungs. PMID- 26859448 TI - TNFalpha-Mediated Cytotoxic Responses to IAP Inhibition Are Limited by the p38alpha MAPK Pathway. AB - Smac mimetics (SMs), a class of drugs that can promote tumor cell death, represent a potential therapeutic strategy for the treatment of cancer. In this issue of Cancer Cell, Lalaoui et al. (2016) report that SM efficacy can be potently increased by inhibition of the p38alpha MAPK/MK2 signaling pathway. PMID- 26859449 TI - miR-126 Drives Quiescence and Self-Renewal in Leukemic Stem Cells. AB - Leukemic stem cells (LSCs) are resistant to conventional chemotherapy and promote acute myeloid leukemia (AML) progression and recurrence. In this issue of Cancer Cell, Lechman and colleagues (2016) identify the microRNA miR-126 as a regulator of PI3K-AKT-mTOR and CDK3 signaling driving LSC self-renewal and chemotherapy resistance. PMID- 26859450 TI - Defining the Molecular Alterations of Ampullary Carcinoma. AB - Ampullary carcinomas represent a group of heterogeneous tumors that can be histologically divided into two subtypes with distinct pathogenic and clinical characteristics. Yachida et al. (2016) and Gingras et al. (2016) now report the genomic landscape of ampullary carcinoma, providing insights into molecular drivers with clinical implications for diagnosis and therapeutics. PMID- 26859451 TI - Fall of the Optical Wall: Freedom from the Tyranny of the Microscope Improves Glioma Risk Stratification. AB - A recent study uses an integrated genomic approach to identify biologically defined subgroups of adult diffuse glioma. These results further lay the foundation for a pathological classification scheme for gliomas that incorporates both histology and molecular biomarkers, which appears far more robust than the current scheme, based solely on morphology. PMID- 26859452 TI - Bringing IDH into the Fold. AB - Glioma-associated mutations in IDH1 or IDH2 lead to aberrant DNA methylation. A recent paper shows that loss of methylation-sensitive CTCF binding in IDH mutant cells leads to disruption of enhancer boundary function, which results in aberrant activation of PDGFRA expression via an enhancer associated with an adjacent gene. PMID- 26859453 TI - A Word of Caution on New and Revolutionary Diagnostic Tests. PMID- 26859454 TI - Re: a Word of Caution on New and Revolutionary Diagnostic Tests. PMID- 26859455 TI - Targeting p38 or MK2 Enhances the Anti-Leukemic Activity of Smac-Mimetics. AB - Birinapant is a smac-mimetic (SM) in clinical trials for treating cancer. SM antagonize inhibitor of apoptosis (IAP) proteins and simultaneously induce tumor necrosis factor (TNF) secretion to render cancers sensitive to TNF-induced killing. To enhance SM efficacy, we screened kinase inhibitors for their ability to increase TNF production of SM-treated cells. We showed that p38 inhibitors increased TNF induced by SM. Unexpectedly, even though p38 is required for Toll like receptors to induce TNF, loss of p38 or its downstream kinase MK2 increased induction of TNF by SM. Hence, we show that the p38/MK2 axis can inhibit or promote TNF production, depending on the stimulus. Importantly, clinical p38 inhibitors overcame resistance of primary acute myeloid leukemia to birinapant. PMID- 26859457 TI - Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers. AB - Netrin-1 has been shown to be up-regulated in a fraction of human cancers as a mechanism to allow these tumors to escape the pro-apoptotic activity of some of its main dependence receptors, the UNC5 homologs (UNC5H). Here we identify the V 2 domain of netrin-1 to be important for its interaction with the Ig1/Ig2 domains of UNC5H2. We generate a humanized anti-netrin-1 antibody that disrupts the interaction between netrin-1 and UNC5H2 and triggers death of netrin-1-expressing tumor cells in vitro. We also present evidence that combining the anti-netrin-1 antibody with epidrugs such as decitabine could be effective in treating tumors showing no or modest netrin-1 expression. These results support that this antibody is a promising drug candidate. PMID- 26859456 TI - Exploitation of the Apoptosis-Primed State of MYCN-Amplified Neuroblastoma to Develop a Potent and Specific Targeted Therapy Combination. AB - Fewer than half of children with high-risk neuroblastoma survive. Many of these tumors harbor high-level amplification of MYCN, which correlates with poor disease outcome. Using data from our large drug screen we predicted, and subsequently demonstrated, that MYCN-amplified neuroblastomas are sensitive to the BCL-2 inhibitor ABT-199. This sensitivity occurs in part through low anti apoptotic BCL-xL expression, high pro-apoptotic NOXA expression, and paradoxical, MYCN-driven upregulation of NOXA. Screening for enhancers of ABT-199 sensitivity in MYCN-amplified neuroblastomas, we demonstrate that the Aurora Kinase A inhibitor MLN8237 combines with ABT-199 to induce widespread apoptosis. In diverse models of MYCN-amplified neuroblastoma, including a patient-derived xenograft model, this combination uniformly induced tumor shrinkage, and in multiple instances led to complete tumor regression. PMID- 26859460 TI - Objective and Subjective Outcome of a New Transcutaneous Bone Conduction Hearing Device: Half-year Follow-up of the First 12 Nordic Implantations. AB - OBJECTIVE: To examine the objective and subjective outcome of a new transcutaneous bone conduction hearing device. STUDY DESIGN: Prospective, consecutive case series. PATIENTS: Twelve patients were implanted. Eight patients had a conductive/mixed (con/mix) hearing loss. Four had single sided deafness. MAIN OUTCOME MEASURES: At half-year follow-up, aided and unaided sound field hearing was evaluated by 1) warble tone thresholds, 2) pure-tone average (PTA4), 3) speech discrimination score (SDS) in quiet, and 4) speech reception threshold 50% at 70 dB SPL noise level (SRT50%). Subjective outcome was evaluated by three questionnaires: 1) International Outcome Inventory for Hearing Aids, 2) Speech, Spatial and Qualities of Hearing Scale 12, and 3) a questionnaire on frequency and duration of use. RESULTS: No major complications occurred. The mean aided PTA4 was lowered by 23dB. SDS was increased by 40% at 50dB, by 34% at 65dB, and by 12% at 80 dB SPL. SRT50% in noise improved 5.2 dB. 58% of the patients used the device daily and 83% at least 5 days a week. 50% used the device >= 8 hours and 75% >= 4 hours a day. Mean International Outcome Inventory for Hearing Aids score was 3.7, corresponding to beneficial outcome. In Speech, Spatial and Qualities of Hearing Scale 12, "quality of hearing" scored especially high. The con/mix hearing loss group showed larger benefit especially in SDS, SRT50% in noise and the subjective evaluations, whereas frequency and duration of use were similar. CONCLUSION: This study on the first 12 Nordic patients implanted with a new transcutaneous bone conduction hearing device demonstrates significant objective, as well as subjective hearing benefit. Patient satisfaction was high, as was the frequency of use. PMID- 26859458 TI - Truncating Erythropoietin Receptor Rearrangements in Acute Lymphoblastic Leukemia. AB - Chromosomal rearrangements are a hallmark of acute lymphoblastic leukemia (ALL) and are important ALL initiating events. We describe four different rearrangements of the erythropoietin receptor gene EPOR in Philadelphia chromosome-like (Ph-like) ALL. All of these rearrangements result in truncation of the cytoplasmic tail of EPOR at residues similar to those mutated in primary familial congenital polycythemia, with preservation of the proximal tyrosine essential for receptor activation and loss of distal regulatory residues. This resulted in deregulated EPOR expression, hypersensitivity to erythropoietin stimulation, and heightened JAK-STAT activation. Expression of truncated EPOR in mouse B cell progenitors induced ALL in vivo. Human leukemic cells with EPOR rearrangements were sensitive to JAK-STAT inhibition, suggesting a therapeutic option in high-risk ALL. PMID- 26859461 TI - Predictive Value of Gait Speed and Frailty Indicators on Survival Time and Time Until Discharge to Home in Ambulant Older Patients in a Specialized Rehabilitation Center. AB - BACKGROUND AND PURPOSE: "Frailty" is a frequently used term in both scientific research and clinical practice, but it has proven to be difficult to recognize and measure frailty. In this study, we aim to identify variables related to frailty as simple and unambiguous predictors of time until discharge to home and until mortality for ambulant individuals residing in a rehabilitation center for older people. METHODS: This was a longitudinal cohort study. We included data on people admitted to a Dutch rehabilitation center for older people between September 15, 2013, and September 10, 2014 (n = 389). At admission, we collected data regarding participants' demography, details of their admission and origin as well as their gait speed. We also asked both participants and their physiotherapists whether the patients experienced problems as a consequence of fatigue, mobility, balance, or unintentional weight loss (yes/no), which are considered to be indicators of frailty. Date of discharge or death was recorded upon occurrence. We used survival analyses to establish associations between frailty indicators and gait speed with time until death and time until discharge to home. RESULTS AND DISCUSSION: We found associations between patients' and physiotherapists' reports regarding indicators of frailty with mortality and discharge to home. Although patients' and physiotherapists' scores were strongly correlated, the physiotherapists' scores proved to be more accurate in predicting time until discharge to home and mortality. Time until death was best predicted by the physiotherapists' report that a patient was fatigued (hazard ratio = 4.09; 95% confidence interval = 1.41-11.83; P < .01). Time until discharge to home was strongly related to physiotherapists' reports of unintentional weight loss in the patient (hazard ratio = 0.67; 95% confidence interval = 0.48-0.95; P < .05). We did not find a relationship between gait speed and time until death and discharge to home. CONCLUSIONS: Simple yes/no reports by physiotherapists at the time of admission regarding patients feeling fatigued and losing weight unintentionally showed strong associations with time until death and time until discharge to home. These simple questions could be used for screening at admission to identify people at risk of prolonged rehabilitation and mortality. PMID- 26859459 TI - Serine/Threonine Kinase MLK4 Determines Mesenchymal Identity in Glioma Stem Cells in an NF-kappaB-dependent Manner. AB - Activation of nuclear factor kappaB (NF-kappaB) induces mesenchymal (MES) transdifferentiation and radioresistance in glioma stem cells (GSCs), but molecular mechanisms for NF-kappaB activation in GSCs are currently unknown. Here, we report that mixed lineage kinase 4 (MLK4) is overexpressed in MES but not proneural (PN) GSCs. Silencing MLK4 suppresses self-renewal, motility, tumorigenesis, and radioresistance of MES GSCs via a loss of the MES signature. MLK4 binds and phosphorylates the NF-kappaB regulator IKKalpha, leading to activation of NF-kappaB signaling in GSCs. MLK4 expression is inversely correlated with patient prognosis in MES, but not PN high-grade gliomas. Collectively, our results uncover MLK4 as an upstream regulator of NF-kappaB signaling and a potential molecular target for the MES subtype of glioblastomas. PMID- 26859462 TI - Explanators of Sarcopenia in Individuals With Diabesity: A Cross-Sectional Analysis. AB - BACKGROUND AND PURPOSE: Excess lower extremity intermuscular adipose tissue (IMAT), reduced strength, and functional limitations are common in obese individuals with and without diabetes (the former termed diabesity). Individuals with diabesity are particularly susceptible to accelerated sarcopenia, which may be underdiagnosed. The purpose of this study was to determine critical values for leg IMAT volume, plantar flexor (PF) muscle strength, and physical performance that help identify individuals with diabesity who have sarcopenia. METHODS: Forty three age- and sex-matched obese adults were studied: 12 with type 2 diabetes, 21 with diabetes and peripheral neuropathy, and 10 nondiabetic controls. Dual-energy x-ray absorptiometry-derived skeletal muscle index determined classification of sarcopenia. Leg fat (% IMAT), ankle (PF) peak torque, and power while ascending 10 steps, were used as explanators of sarcopenia. Receiver operating curves identified critical values for each explanator individually. Logistic regression models using all 3 explanators, and only PF torque and stair power, were also created. Receiver operating curve analyses identified the predicted probability that maximized each model's sensitivity and specificity. A leave-one-out cross validation was used to simulate the models' performance in an independent sample. RESULTS AND DISCUSSION: Thirty-two participants were sarcopenic, and 11 were not. Critical values for individual explanators were 21% IMAT, 68 Nm PF torque, and 441 watts of stair power. Predicted probabilities of .76 and .67 were chosen as the optimal cutoff probabilities for the model combining all 3 explanators, and the model combining PF torque and stair power, respectively. The cross-validation analysis produced an accuracy of 82.4%, using the cutoff probability of .5, and an accuracy of 76.5% using the cutoff of 0.76. The area under the curve for the cross validation receiver operating curve analysis was 0.82. Critical values of leg % IMAT, PF torque, and stair power can classify individuals with diabesity as sarcopenic. The results of the cross validation give us confidence that the sample used in this study was representative of the target population, and suggests models created from this sample may perform well in externally derived data sets. CONCLUSION: Clinicians may be able to use these critical values to select interventions that specifically target sarcopenia. Measures of % IMAT, PF torque, and stair power may offer a customized alternative to traditional sarcopenic classification systems, which may not be optimally suited to the common impairments among individuals with diabesity. PMID- 26859463 TI - Short- and Long-Term Effects of Balance Training on Physical Activity in Older Adults With Osteoporosis: A Randomized Controlled Trial. AB - BACKGROUND AND PURPOSE: We have developed a 12-week balance training program for older adults shown to improve fall-related concerns, gait speed, balance performance, and physical function. We hypothesized that this balance training would also contribute to higher habitual physical activity (PA) levels and improved health-related quality of life (HRQoL). The primary aim was to evaluate short- and long-term effects of the balance training program on objectively measured habitual PA in older adults with osteoporosis. Secondary aims were to assess the effects of the balance training on HRQoL, and to study whether any effects on PA were associated with changes in HRQoL, gait speed, balance performance, fall-related concerns, and physical function. METHODS: A randomized controlled trial with follow-up at 3, 9, and 15 months, including 91 participants with osteoporosis (75.6 +/- 5.4 years), compared a balance training group (n = 61) with a control group (n = 30). The primary outcome was effect on habitual PA measured as steps/day, dichotomized into less than 5000 or 5000 or more steps/day. Physical activity was assessed with pedometers (Yamax) and accelerometers (Actigraph), HRQoL with the Short Form-36 (SF-36), gait with a GAITRite walkway, balance performance with Modified-Figure-Eight test and one-leg stance, fall-related concerns with Falls Efficacy Scale International, and physical function with the advanced lower extremity subscale of the questionnaire Late Life Function and Disability Instrument. Statistical methods used were multivariate logistic regression and logistic generalized estimating equation. RESULTS: Sixty-eight participants completed the short-term follow-up at 3 months, and 53 participants completed the long-term follow-up at 15 months. Per-protocol analysis (n = 68) showed that the odds ratio for having a daily step count of 5000 or more at 3 months was 6.17 (95% confidence interval, 1.23-30.91), P = .027, for the intervention group compared with the control group. The longitudinal analysis (n = 91) showed that the odds ratio for having a daily step count of 5000 or more at 15 months was 2.02 (95% confidence interval, 0.88-4.64), P = .096, for the intervention group compared with the control group. The mental component sum of the SF-36 improved significantly from baseline to 3 months in the intervention group, and the physical component sum improved in both groups, but no statistically significant differences were found between groups. No associations were found between PA and changes in covariates. DISCUSSION AND CONCLUSIONS: The short-term evaluation showed that balance training increased habitual PA in community-dwelling older adults with osteoporosis. A significantly higher proportion of participants in the intervention group reached a level of 5000 or more steps/day, which is important for overall health. This effect was not associated with improvements in HRQoL, gait speed, balance performance, or fall-related concerns, and did not persist through the long-term follow-up. To accomplish a sustained PA change, a prolonged intervention or more support regarding habitual PA may be required, such as reinforcement with personalized behavior change counseling or PA on prescription. PMID- 26859464 TI - Association of the Metabolic Syndrome with Antioxidant Defense and Outstanding Superoxide Dismutase Activity in Mexican Subjects. AB - BACKGROUND: Metabolic syndrome (MetS) is considered a public health problem worldwide. Recently, oxidative stress (OS) has been proposed as a factor related with the genesis of MetS. Different studies have reported decreased antioxidant defense, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRed) activities, and reduced glutathione (GSH) concentration, and, on the other hand, an increase in nitrotyrosine concentration in MetS patients. However, it is not known whether there is a direct association of antioxidant defense with MetS in a Mexican population. The aim of the study was to determine the relationship between antioxidant defense and MetS in Mexican subjects. MATERIALS AND METHODS: The subjects were Mexican mestizos, who were anthropometrically, biochemically, and clinically characterized. MetS was diagnosed by National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III)-modified criteria. Antioxidant defense was determined by activity of SOD, GPx, GRed, and GSH concentrations; as a marker of OS, nitrotyrosine concentration was determined. RESULTS: The study included 376 subjects, among whom 152 subjects had MetS and 224 were assigned to the non-MetS group. Statistical association was found between MetS and SOD activity (Odds ratio: 167.1; P < 0.01; adjusted by age, gender, and waist circumference). It is noteworthy that a significant correlation between antioxidant defense (SOD and GPx activities, and GSH) and different MetS components was found and between MetS and nitrotyrosine concentration (P < 0.05). CONCLUSION: The results indicate that SOD activity is associated with MetS in Mexican subjects, allowing us to suggest that this enzyme plays an important role in the pathophysiology of MetS. PMID- 26859465 TI - Corrigendum: Bridging the gap between in vitro and in vivo: Dose and schedule predictions for the ATR inhibitor AZD6738. PMID- 26859466 TI - Nonobstetric anesthesia during pregnancy. AB - PURPOSE OF REVIEW: Nonobstetric anesthesia during pregnancy is challenging - not only for the anesthetist. Owing to the difficulties of ethical consent for randomized studies in this special patient group, the available evidence is quite low. Nevertheless, recently several guidelines for the management of pregnant patients undergoing nonobstetric anesthesia have been published. We review the current guidelines developed under the auspices of the Society of American Gastrointestinal Endoscopic Surgeons, guidelines for the management of difficult and failed tracheal intubation in obstetrics, as well as guidelines for the management of a pregnant trauma patient. RECENT FINDINGS: The algorithms for management of the difficult airway during pregnancy should be made available in every institution that cares for pregnant women. During laparoscopic surgery strict limitation of the pneumoperitoneal pressure to avoid maternal hypercapnia and fetal acidosis is strongly recommended. An injured pregnant woman should be transferred to a maternity facility when the injury is not life or limb threatening. In case of major trauma, stabilization and care of the woman is priority. SUMMARY: Several guidelines with high relevance for the care of pregnant women undergoing nonobstetric surgery have been published. Although the level of evidence may be low they can probably contribute to an improvement in the care and outcome of this patient group. PMID- 26859467 TI - Randomized Controlled Trial of Use of the Peanut Ball During Labor. AB - PURPOSE: The purpose of this study was to evaluate the efficacy of peanut ball use on duration of first stage labor and pushing time in women who were scheduled for elective induction of labor at >=39 weeks gestation and planning an epidural. STUDY DESIGN AND METHODS: In this randomized controlled trial, women having labor induction and planning a labor epidural were assigned (1:1) to one of two groups: one group used a peanut ball and one group did not. Outcome variables were time spent in first stage labor and time spent pushing. Factors included group assignment (peanut ball, no peanut ball), parity (primiparous, multiparous), and race. Age and maximum oxytocin dose served as covariates. RESULTS: Among women having elective induction with epidural analgesia, use of a peanut ball reduced first stage labor duration for primiparous patients significantly more than multiparous patients, p = 0.018. There was no significant difference in the reduction of length of first stage labor for multiparous women, p = 0.057 with use of the peanut ball. Peanut ball use did not alter length of pushing time for either group, p > 0.05. CLINICAL IMPLICATIONS: Use of peanut balls may reduce total labor time to a greater degree in primiparous patients than multiparous patients having elective induction at >=39 weeks with epidural analgesia. PMID- 26859468 TI - [Not Available]. PMID- 26859469 TI - [Case report: resuscitation of a hypothermic patient - "Nothing's like it seems!"]. AB - We report about a prolonged resuscitation of a hypothermic patient (26.2 degrees C) in stadium HT III of the Swiss Staging System (SSS). A mechanical chest compression with the Lund University Cardiac Assist System (LUCAS) and the rewarming with a haemodialysis device were implemented. After a resuscitation time of 200min and a body temperature of 32.1 degrees C ventricular fibrillation occurred. After the defibrillation a return of spontaneous circulation (ROSC) was established. The patient achieved a very good cognitive-mnestic result after the resuscitation but he suffered a neurological deficit in the meaning of paraplegia. PMID- 26859470 TI - [Case Report: Zinc phosphide poisoning after ingestion of a rodentizide in suicidal intention]. AB - Zinc phosphide normally serves as a rodenticide but is occasionally ingested for suicide, potentially causing multiorgan failure. Phosphine gas is commonly in use for fumigation of grain silos and shipping containers.We describe a suicide attempt of a 54 year old female, the clinical symptoms, the treatment, the chemical and biochemical background and we give information on the potential occurrence of zinc phosphide and phosphine gas. PMID- 26859471 TI - [Emergency medicine at the limit: shock-, analgesic therapy and airway management in difficult terrain]. AB - Rescue operations in mountain and remote areas pose special challenges for the rescue team and often differ substantially from rescue missions in the urban environment. Given the growing sports and leisure activities in mountains, incidence of alpine emergencies is expected to rise further. The following article describes the treatment of haemorrhagic shock, analgesic therapy and airway management in mountain rescue. PMID- 26859472 TI - [Not Available]. PMID- 26859473 TI - [Quality improvement in acute pain management in Germany]. AB - In Germany, different quality management approaches in postoperative pain management have been established. In this context, quality is distinguished into structure quality (e.g. personnel and equipment resources), process quality (e. g. standardized treatment schemes) and outcome quality (e.g. pain intensity, side effects, satisfaction). While guidelines and recommendations help to set up evidence based structures and processes and offer support for decision making, benchmark projects offer insights in real life conditions. By use of feedback and benchmarking tools, they can be used for outcome-oriented quality improvement. Certification projects assess compliance with or achievement of defined quality criteria on the basis of predefined structure, process, and outcome parameter. PMID- 26859474 TI - [Multimodal pain therapy in Germany: structure and quality]. AB - Multimodal Pain Management is a comprehensive treatment of complex chronic pain syndromes. In addition to medical therapy various other specialized therapeutical interventions based on the biopsychosocial model of pain origin and chronic pain development are added.Medical indications are given for patients with chronic pain syndromes, but also if there is an elevated risk of chronic pain in the early stadium of the disease and aiming at delaying the process of chronification. Multimodal pain management has been included in the official catalogue of the recognized medical procedure for day clinic units as well as for inpatients pain management. As there is still a lack of clarity and of consistency about the implementation of multimodal pain management the ad-hoc Kommission on multimodal interdisciplinary pain management of the German Pain Society has proposed a position paper that has been worked out in a multilevel and interdisciplinary consensus process. Moreover a basic tool for documentation and quality management of pain therapy was developed by the German Pain Society (KEDOQ-Schmerz) as the data basis for nationwide, cross-sectional and independent scientific research in health services in Germany. In future KEDOQ-Schmerz will also used as a method for external quality management in chronic pain therapy in Germany. PMID- 26859477 TI - [Not Available]. PMID- 26859480 TI - Synthesis, characterization, DFT calculations, and electrochemical comparison of novel iron(ii) complexes with thione and selone ligands. AB - Thione- and selone-containing compounds and their metal complexes show promise as antioxidants, as antithyroid drugs, and for applications in lasers and blue light emitting diodes. Although Cu(i/ii), Co(ii), Ag(i), and Zn(ii) coordination to thione and selone ligands has been broadly studied and Fe(ii) plays an important role in oxidative damage, very few iron-thione complexes and no iron-selone complexes are reported. Novel Fe(ii)-containing thione and selone complexes of the formulae FeL2Cl2, [FeL2(CH3CN)2](2+), and [FeL4](2+), and {FeL'Cl2}n, (L = N,N'-dimethylimidazole selone (dmise), and thione (dmit); L' = bis(thioimidazolyl)ethane (ebit) and bis(selenoimidazolyl)ethane (ebis)) have been synthesized and characterized. Structures of Fe(dmise)2Cl2, Fe(dmit)2Cl2, [Fe(dmit)4][BF4]2, [Fe(dmise)4][BF4]2, and {Fe(ebit)Cl2}n were determined by X ray crystallography. All Fe(ii) centers adopt a distorted tetrahedral coordination geometry with Fe-S distances ranging from 2.339(1) to 2.397(1) A and F-Se distances ranging from 2.453(1) to 2.514(1) A. Density functional theory optimized structures of FeL2Cl2, [FeL2(CH3CN)2](2+), and [FeL4](2+) are consistent with experimental results and suggest that thiones and selones are pi donor ligands that coordinate through their zwitterionic resonance structures. Thione and selone coordination to Fe(ii) lowers the Fe(ii/iii) reduction potential, with a greater decrease for Fe(ii)-bound dmise than Fe(ii)-bound dmit. Dmit and dmise ligand-based oxidation potentials also significantly increase upon Fe(ii) binding compared, indicating that bound thione and selone ligands will undergo oxidation prior to Fe(ii). The synthesis of these complexes suggests that iron coordination by thione and selone ligands may occur in vivo and may contribute to the protective antioxidant properties of sulfur and selenium. PMID- 26859478 TI - Anti-inflammatory panacea? The expanding therapeutics of interleukin-1 blockade. AB - PURPOSE OF REVIEW: Blockade of interleukin (IL)-1 signaling is one of the oldest biologic therapies, yet the use of these agents is on the rise as the role of IL 1 activation is being recognized in a wide spectrum of inflammatory disorders. This review will cover established and emerging uses of IL-1 antagonism in rheumatic diseases. RECENT FINDINGS: Expanding off-label indications for IL-1 blockade include neutrophil-dominant skin diseases, including pyoderma gangrenosum, hidradenitis supperativa, and pustular psoriasis. There is also increasing evidence for the use of IL-1 blockade in heart failure associated with rheumatic diseases. Somatic mosaicism in NLRP3 may explain the onset of later-in life presentations of periodic fevers which are responsive to IL-1 blockade. Of importance, clinical response to anti-IL-1 therapy does not always denote protection from autoinflammatory disease complications such as macrophage activation syndrome or amyloidosis. SUMMARY: Indications for IL-1 blocking therapies will likely continue to broaden, but given the rarity of many rheumatic diseases which respond to such treatment, rigorous, large clinical trials for each indication are unlikely to occur. Thus, recommended use of these medications will often fall to the discretion of the astute physician. However, medication cost and hurdles of insurance approval, rather than drug efficacy, may be the primary limitation for more widespread use. PMID- 26859481 TI - Effect of Short-Term Supplementation with Ready-to-Use Therapeutic Food or Micronutrients for Children after Illness for Prevention of Malnutrition: A Randomised Controlled Trial in Uganda. AB - BACKGROUND: Globally, Medecins Sans Frontieres (MSF) treats more than 300,000 severely malnourished children annually. Malnutrition is not only caused by lack of food but also by illnesses and by poor infant and child feeding practices. Breaking the vicious cycle of illness and malnutrition by providing ill children with nutritional supplementation is a potentially powerful strategy for preventing malnutrition that has not been adequately investigated. Therefore, MSF investigated whether incidence of malnutrition among ill children <5 y old could be reduced by providing a fortified food product or micronutrients during their 2 wk convalescence period. Two trials, one in Nigeria and one in Uganda, were conducted; here, we report on the trial that took place in Kaabong, a poor agropastoral region of Karamoja, in east Uganda. While the region of Karamoja shows an acute malnutrition rate between 8.4% and 11.5% of which 2% to 3% severe malnutrition, more than half (58%) of the population in the district of Kaabong is considered food insecure. METHODS AND FINDINGS: We investigated the effect of two types of nutritional supplementation on the incidence of malnutrition in ill children presenting at outpatient clinics during March 2011 to April 2012 in Kaabong, Karamoja region, Uganda, a resource-poor region where malnutrition is a chronic problem for its seminomadic population. A three-armed, partially-blinded, randomised controlled trial was conducted in children diagnosed with malaria, diarrhoea, or lower respiratory tract infection. Non-malnourished children aged 6 to 59 mo were randomised to one of three arms: one sachet/d of ready-to-use therapeutic food (RUTF), two sachets/d of micronutrient powder (MNP), or no supplement (control) for 14 d for each illness over 6 mo. The primary outcome was the incidence of first negative nutritional outcome (NNO) during the 6 mo follow up. NNO was a study-specific measure used to indicate progression to moderate or severe acute malnutrition; it was defined as weight-for-height z-score <-2, mid upper arm circumference (MUAC) <115 mm, or oedema, whichever came first. Of the 2,202 randomised participants, 51.2% were girls, and the mean age was 25.2 (+/ 13.8) mo; 148 (6.7%) participants were lost to follow-up, 9 (0.4%) died, and 14 (0.6%) were admitted to hospital. The incidence rates of NNO (first event/year) for the RUTF, MNP, and control groups were 0.143 (95% confidence interval [CI], 0.107-0.191), 0.185 (0.141-0.239), and 0.213 (0.167-0.272), respectively. The incidence rate ratio was 0.67 (95% CI, 0.46-0.98; p = 0.037) for RUTF versus control; a reduction of 33.3%. The incidence rate ratio was 0.86 (0.61-1.23; p = 0.413) for MNP versus control and 0.77 for RUTF versus MNP (95% CI 0.52-1.15; p = 0.200). The average numbers of study illnesses for the RUTF, MNP, and control groups were 2.3 (95% CI, 2.2-2.4), 2.1 (2.0-2.3), and 2.3 (2.2-2.5). The proportions of children who died in the RUTF, MNP, and control groups were 0%, 0.8%, and 0.4%. The findings apply to ill but not malnourished children and cannot be generalised to a general population including children who are not necessarily ill or who are already malnourished. CONCLUSIONS: A 2-wk nutrition supplementation programme with RUTF as part of routine primary medical care to non-malnourished children with malaria, LRTI, or diarrhoea proved effective in preventing malnutrition in eastern Uganda. The low incidence of malnutrition in this population may warrant a more targeted intervention to improve cost effectiveness. TRIAL REGISTRATION: clinicaltrials.gov NCT01497236. PMID- 26859482 TI - Robust DNA Damage Response and Elevated Reactive Oxygen Species in TINF2-Mutated Dyskeratosis Congenita Cells. AB - Dyskeratosis Congenita (DC) is an inherited multisystem premature aging disorder with characteristic skin and mucosal findings as well as a predisposition to cancer and bone marrow failure. DC arises due to gene mutations associated with the telomerase complex or telomere maintenance, resulting in critically shortened telomeres. The pathogenesis of DC, as well as several congenital bone marrow failure (BMF) syndromes, converges on the DNA damage response (DDR) pathway and subsequent elevation of reactive oxygen species (ROS). Historically, DC patients have had poor outcomes following bone marrow transplantation (BMT), perhaps as a consequence of an underlying DNA hypersensitivity to cytotoxic agents. Previously, we demonstrated an activated DDR and increased ROS, augmented by chemotherapy and radiation, in somatic cells isolated from DC patients with a mutation in the RNA component of telomerase, TERC. The current study was undertaken to determine whether previous findings related to ROS and DDR in TERC patients' cells could be extended to other DC mutations. Of particular interest was whether an antioxidant approach could counter increased ROS and decrease DC pathologies. To test this, we examined lymphocytes from DC patients from different DC mutations (TERT, TINF2, and TERC) for the presence of an active DDR and increased ROS. All DC mutations led to increased steady-state p53 (2-fold to 10-fold) and ROS (1.5-fold to 2-fold). Upon exposure to ionizing radiation (XRT), DC cells increased in both DDR and ROS to a significant degree. Exposing DC cells to hydrogen peroxide also revealed that DC cells maintain a significant oxidant burden compared to controls (1.5-fold to 3-fold). DC cell culture supplemented with N-acetylcysteine, or alternatively grown in low oxygen, afforded significant proliferative benefits (proliferation: maximum 2-fold increase; NAC: 5-fold p53 decrease; low oxygen: maximum 3.5-fold p53 decrease). Together, our data supports a mechanism whereby telomerase deficiency and subsequent shortened telomeres initiate a DDR and create a pro-oxidant environment, especially in cells carrying the TINF2 mutations. Finally, the ameliorative effects of antioxidants in vitro suggest this could translate to therapeutic benefits in DC patients. PMID- 26859483 TI - Effects of Genotype and Growth Temperature on the Contents of Tannin, Phytate and In Vitro Iron Availability of Sorghum Grains. AB - BACKGROUND: It has been predicted that the global temperature will rise in the future, which means crops including sorghum will likely be grown under higher temperatures, and consequently may affect the nutritional properties. METHODS: The effects of two growth temperatures (OT, day/night 32/21 degrees C; HT 38/21 degrees C) on tannin, phytate, mineral, and in vitro iron availability of raw and cooked grains (as porridge) of six sorghum genotypes were investigated. RESULTS: Tannin content significantly decreased across all sorghum genotypes under high growth temperature (P <=0.05), while the phytate and mineral contents maintained the same level, increased or decreased significantly, depending on the genotype. The in vitro iron availability in most sorghum genotypes was also significantly reduced under high temperature, except for Ai4, which showed a pronounced increase (P <=0.05). The cooking process significantly reduced tannin content in all sorghum genotypes (P <=0.05), while the phytate content and in vitro iron availability were not significantly affected. CONCLUSIONS: This research provides some new information on sorghum grain nutritional properties when grown under predicted future higher temperatures, which could be important for humans where sorghum grains are consumed as staple food. PMID- 26859484 TI - The Psychometric Evaluation of the Connor-Davidson Resilience Scale Using a Chinese Military Sample. AB - This study examined the psychometric properties of the Connor-Davidson Resilience Scale (CD-RISC) with a Chinese military population with the aim of finding a suitable instrument to quantify resilience in Chinese military service members. The confirmatory factor analysis results did not support the factorial structure of the original or the Chinese community version of the CD-RISC, but the exploratory factor analysis results revealed a three-factor model (composed of Competency, Toughness, and Adaptability) that seemed to fit. Moreover, the repeat confirmatory factory analysis replicated the three-factor model. Additionally, the CD-RISC with a Chinese military sample exhibited appropriate psychometric properties, including internal consistency, test-retest reliability, and structural and concurrent validity. The revised CD-RISC with a Chinese military sample provides insight into the resilience measurement framework and could be a reliable and valid measurement for evaluating resilience in a Chinese military population. PMID- 26859485 TI - Bayesian Methods for Medical Test Accuracy. AB - Bayesian methods for medical test accuracy are presented, beginning with the basic measures for tests with binary scores: true positive fraction, false positive fraction, positive predictive values, and negative predictive value. The Bayesian approach is taken because of its efficient use of prior information, and the analysis is executed with a Bayesian software package WinBUGS(r). The ROC (receiver operating characteristic) curve gives the intrinsic accuracy of medical tests that have ordinal or continuous scores, and the Bayesian approach is illustrated with many examples from cancer and other diseases. Medical tests include X-ray, mammography, ultrasound, computed tomography, magnetic resonance imaging, nuclear medicine and tests based on biomarkers, such as blood glucose values for diabetes. The presentation continues with more specialized methods suitable for measuring the accuracies of clinical studies that have verification bias, and medical tests without a gold standard. Lastly, the review is concluded with Bayesian methods for measuring the accuracy of the combination of two or more tests. PMID- 26859486 TI - Flow-Mediated Vasodilatation and Intima-Media Thickness in Patients with Coexisting Heart Failure and Diabetes Receiving Medical Therapy. AB - OBJECTIVE: Intensive medical treatment of heart failure (HF) patients with diabetes may reduce the endothelial dysfunction and the accelerated atherosclerotic process seen in these patients. To study this, we investigated the endothelial function and the presence of atherosclerosis as measured by flow mediated vasodilatation (FMD) and intima-media thickness (IMT) in intensively treated patients with coexisting HF and diabetes. RESEARCH DESIGN AND METHOD: FMD of the brachial artery and IMT of the common carotid arteries were determined in 26 patients with systolic HF and diabetes who were in intensive medical therapy, as well as in 19 healthy controls. The two groups were matched according to age and sex. In all subjects left ventricular ejection fraction was measured by two dimensional echocardiography. Biochemical parameters including serum cholesterol, HDL and LDL, triglyceride, glucose, hemoglobin/hemoglobin-A1C (HbA1C), brain natriuretic peptide (BNP) and N-terminal pro-BNP were also assessed. RESULTS: Mean FMD and IMT did not differ significantly between patients and controls. Left ventricular ejection fraction was lower in patients compared to controls (P < 0.001). The patients had a higher mean BNP, NT pro-BNP, triglyceride, HbA1C and glucose in comparison to controls. Cholesterol, HDL-cholesterol and LDL cholesterol were lower in patients compared to controls. CONCLUSIONS: Intensively treated patients with coexisting systolic HF and diabetes seem to have normal endothelial function as measured by FMD and they have no sign of accelerated atherosclerosis as measured by IMT. This suggests a positive effect of medication on the cardiovascular alterations in this group of patients. PMID- 26859487 TI - Bayesian Estimation of Combined Accuracy for Tests with Verification Bias. AB - This presentation will emphasize the estimation of the combined accuracy of two or more tests when verification bias is present. Verification bias occurs when some of the subjects are not subject to the gold standard. The approach is Bayesian where the estimation of test accuracy is based on the posterior distribution of the relevant parameter. Accuracy of two combined binary tests is estimated employing either "believe the positive" or "believe the negative" rule, then the true and false positive fractions for each rule are computed for two tests. In order to perform the analysis, the missing at random assumption is imposed, and an interesting example is provided by estimating the combined accuracy of CT and MRI to diagnose lung cancer. The Bayesian approach is extended to two ordinal tests when verification bias is present, and the accuracy of the combined tests is based on the ROC area of the risk function. An example involving mammography with two readers with extreme verification bias illustrates the estimation of the combined test accuracy for ordinal tests. PMID- 26859488 TI - Fast Census of Moth Diversity in the Neotropics: A Comparison of Field-Assigned Morphospecies and DNA Barcoding in Tiger Moths. AB - The morphological species delimitations (i.e. morphospecies) have long been the best way to avoid the taxonomic impediment and compare insect taxa biodiversity in highly diverse tropical and subtropical regions. The development of DNA barcoding, however, has shown great potential to replace (or at least complement) the morphospecies approach, with the advantage of relying on automated methods implemented in computer programs or even online rather than in often subjective morphological features. We sampled moths extensively for two years using light traps in a patch of the highly endangered Atlantic Forest of Brazil to produce a nearly complete census of arctiines (Noctuoidea: Erebidae), whose species richness was compared using different morphological and molecular approaches (DNA barcoding). A total of 1,075 barcode sequences of 286 morphospecies were analyzed. Based on the clustering method Barcode Index Number (BIN) we found a taxonomic bias of approximately 30% in our initial morphological assessment. However, a morphological reassessment revealed that the correspondence between morphospecies and molecular operational taxonomic units (MOTUs) can be up to 94% if differences in genitalia morphology are evaluated in individuals of different MOTUs originated from the same morphospecies (putative cases of cryptic species), and by recording if individuals of different genders in different morphospecies merge together in the same MOTU (putative cases of sexual dimorphism). The results of two other clustering methods (i.e. Automatic Barcode Gap Discovery and 2% threshold) were very similar to those of the BIN approach. Using empirical data we have shown that DNA barcoding performed substantially better than the morphospecies approach, based on superficial morphology, to delimit species of a highly diverse moth taxon, and thus should be used in species inventories. PMID- 26859489 TI - The Metagenome of Utricularia gibba's Traps: Into the Microbial Input to a Carnivorous Plant. AB - The genome and transcriptome sequences of the aquatic, rootless, and carnivorous plant Utricularia gibba L. (Lentibulariaceae), were recently determined. Traps are necessary for U. gibba because they help the plant to survive in nutrient deprived environments. The U. gibba's traps (Ugt) are specialized structures that have been proposed to selectively filter microbial inhabitants. To determine whether the traps indeed have a microbiome that differs, in composition or abundance, from the microbiome in the surrounding environment, we used whole genome shotgun (WGS) metagenomics to describe both the taxonomic and functional diversity of the Ugt microbiome. We collected U. gibba plants from their natural habitat and directly sequenced the metagenome of the Ugt microbiome and its surrounding water. The total predicted number of species in the Ugt was more than 1,100. Using pan-genome fragment recruitment analysis, we were able to identify to the species level of some key Ugt players, such as Pseudomonas monteilii. Functional analysis of the Ugt metagenome suggests that the trap microbiome plays an important role in nutrient scavenging and assimilation while complementing the hydrolytic functions of the plant. PMID- 26859490 TI - Comprehensive Expression of Wnt Signaling Pathway Genes during Development and Maturation of the Mouse Cochlea. AB - BACKGROUND: In the inner ear Wnt signaling is necessary for proliferation, cell fate determination, growth of the cochlear duct, polarized orientation of stereociliary bundles, differentiation of the periotic mesenchyme, and homeostasis of the stria vascularis. In neonatal tissue Wnt signaling can drive proliferation of cells in the sensory region, suggesting that Wnt signaling could be used to regenerate the sensory epithelium in the damaged adult inner ear. Manipulation of Wnt signaling for regeneration will require an understanding of the dynamics of Wnt pathway gene expression in the ear. We present a comprehensive screen for 84 Wnt signaling related genes across four developmental and postnatal time points. RESULTS: We identified 72 Wnt related genes expressed in the inner ear on embryonic day (E) 12.5, postnatal day (P) 0, P6 and P30. These genes included secreted Wnts, Wnt antagonists, intracellular components of canonical signaling and components of non-canonical signaling/planar cell polarity. CONCLUSION: A large number of Wnt signaling molecules were dynamically expressed during cochlear development and in the early postnatal period, suggesting complex regulation of Wnt transduction. The data revealed several potential key regulators for further study. PMID- 26859492 TI - Instrumenting Beliefs in Threshold Public Goods. AB - Understanding the causal impact of beliefs on contributions in Threshold Public Goods (TPGs) is particularly important since the social optimum can be supported as a Nash Equilibrium and best-response contributions are a function of beliefs. Unfortunately, investigations of the impact of beliefs on behavior are plagued with endogeneity concerns. We create a set of instruments by cleanly and exogenously manipulating beliefs without deception. Tests indicate that the instruments are valid and relevant. Perhaps surprisingly, we fail to find evidence that beliefs are endogenous in either the one-shot or repeated-decision settings. TPG allocations are determined by a base contribution and beliefs in a one shot-setting. In the repeated-decision environment, once we instrument for first-round allocations, we find that second-round allocations are driven equally by beliefs and history. Moreover, we find that failing to instrument prior decisions overstates their importance. PMID- 26859494 TI - Proposed Standards for Variable Harmonization Documentation and Referencing: A Case Study Using QuickCharmStats 1.1. AB - Comparative statistical analyses often require data harmonization, yet the social sciences do not have clear operationalization frameworks that guide and homogenize variable coding decisions across disciplines. When faced with a need to harmonize variables researchers often look for guidance from various international studies that employ output harmonization, such as the Comparative Survey of Election Studies, which offer recoding structures for the same variable (e.g. marital status). More problematically there are no agreed documentation standards or journal requirements for reporting variable harmonization to facilitate a transparent replication process. We propose a conceptual and data driven digital solution that creates harmonization documentation standards for publication and scholarly citation: QuickCharmStats 1.1. It is free and open source software that allows for the organizing, documenting and publishing of data harmonization projects. QuickCharmStats starts at the conceptual level and its workflow ends with a variable recording syntax. It is therefore flexible enough to reflect a variety of theoretical justifications for variable harmonization. Using the socio-demographic variable 'marital status', we demonstrate how the CharmStats workflow collates metadata while being guided by the scientific standards of transparency and replication. It encourages researchers to publish their harmonization work by providing researchers who complete the peer review process a permanent identifier. Those who contribute original data harmonization work to their discipline can now be credited through citations. Finally, we propose peer-review standards for harmonization documentation, describe a route to online publishing, and provide a referencing format to cite harmonization projects. Although CharmStats products are designed for social scientists our adherence to the scientific method ensures our products can be used by researchers across the sciences. PMID- 26859493 TI - Assessment of the Microbial Constituents of the Home Environment of Individuals with Cystic Fibrosis (CF) and Their Association with Lower Airways Infections. AB - INTRODUCTION: Cystic fibrosis (CF) airways are colonized by a polymicrobial community of organisms, termed the CF microbiota. We sought to define the microbial constituents of the home environment of individuals with CF and determine if it may serve as a latent reservoir for infection. METHODS: Six patients with newly identified CF pathogens were included. An investigator collected repeat sputum and multiple environmental samples from their homes. Bacteria were cultured under both aerobic and anaerobic conditions. Morphologically distinct colonies were selected, purified and identified to the genus and species level through 16S rRNA gene sequencing. When concordant organisms were identified in sputum and environment, pulsed-field gel electrophoresis (PFGE) was performed to determine relatedness. Culture independent bacterial profiling of each sample was carried out by Illumina sequencing of the V3 region of the 16s RNA gene. RESULTS: New respiratory pathogens prompting investigation included: Mycobacterium abscessus(2), Stenotrophomonas maltophilia(3), Pseudomonas aeruginosa(3), Pseudomonas fluorescens(1), Nocardia spp.(1), and Achromobacter xylosoxidans(1). A median 25 organisms/patient were cultured from sputum. A median 125 organisms/home were cultured from environmental sites. Several organisms commonly found in the CF lung microbiome were identified within the home environments of these patients. Concordant species included members of the following genera: Brevibacterium(1), Microbacterium(1), Staphylococcus(3), Stenotrophomonas(2), Streptococcus(2), Sphingomonas(1), and Pseudomonas(4). PFGE confirmed related strains (one episode each of Sphinogomonas and P. aeruginosa) from the environment and airways were identified in two patients. Culture-independent assessment confirmed that many organisms were not identified using culture-dependent techniques. CONCLUSIONS: Members of the CF microbiota can be found as constituents of the home environment in individuals with CF. While the majority of isolates from the home environment were not genetically related to those isolated from the lower airways of individuals with CF suggesting alternate sources of infection were more common, a few genetically related isolates were indeed identified. As such, the home environment may rarely serve as either the source of infection or a persistent reservoir for re-infection after clearance. PMID- 26859495 TI - Association between Ability Emotional Intelligence and Left Insula during Social Judgment of Facial Emotions. AB - The human ability of identifying, processing and regulating emotions from social stimuli is generally referred as Emotional Intelligence (EI). Within EI, Ability EI identifies a performance measure assessing individual skills at perceiving, using, understanding and managing emotions. Previous models suggest that a brain "somatic marker circuitry" (SMC) sustains emotional sub-processes included in EI. Three primary brain regions are included: the amygdala, the insula and the ventromedial prefrontal cortex (vmPFC). Here, our aim was to investigate the relationship between Ability EI scores and SMC activity during social judgment of emotional faces. Sixty-three healthy subjects completed a test measuring Ability EI and underwent fMRI during a social decision task (i.e. approach or avoid) about emotional faces with different facial expressions. Imaging data revealed that EI scores are associated with left insula activity during social judgment of emotional faces as a function of facial expression. Specifically, higher EI scores are associated with greater left insula activity during social judgment of fearful faces but also with lower activity of this region during social judgment of angry faces. These findings indicate that the association between Ability EI and the SMC activity during social behavior is region- and emotion-specific. PMID- 26859496 TI - Experimental Manipulation of Grassland Plant Diversity Induces Complex Shifts in Aboveground Arthropod Diversity. AB - Changes in producer diversity cause multiple changes in consumer communities through various mechanisms. However, past analyses investigating the relationship between plant diversity and arthropod consumers focused only on few aspects of arthropod diversity, e.g. species richness and abundance. Yet, shifts in understudied facets of arthropod diversity like relative abundances or species dominance may have strong effects on arthropod-mediated ecosystem functions. Here we analyze the relationship between plant species richness and arthropod diversity using four complementary diversity indices, namely: abundance, species richness, evenness (equitability of the abundance distribution) and dominance (relative abundance of the dominant species). Along an experimental gradient of plant species richness (1, 2, 4, 8, 16 and 60 plant species), we sampled herbivorous and carnivorous arthropods using pitfall traps and suction sampling during a whole vegetation period. We tested whether plant species richness affects consumer diversity directly (i), or indirectly through increased productivity (ii). Further, we tested the impact of plant community composition on arthropod diversity by testing for the effects of plant functional groups (iii). Abundance and species richness of both herbivores and carnivores increased with increasing plant species richness, but the underlying mechanisms differed between the two trophic groups. While higher species richness in herbivores was caused by an increase in resource diversity, carnivore richness was driven by plant productivity. Evenness of herbivore communities did not change along the gradient in plant species richness, whereas evenness of carnivores declined. The abundance of dominant herbivore species showed no response to changes in plant species richness, but the dominant carnivores were more abundant in species-rich plant communities. The functional composition of plant communities had small impacts on herbivore communities, whereas carnivore communities were affected by forbs of small stature, grasses and legumes. Contrasting patterns in the abundance of dominant species imply different levels of resource specialization for dominant herbivores (narrow food spectrum) and carnivores (broad food spectrum). That in turn could heavily affect ecosystem functions mediated by herbivorous and carnivorous arthropods, such as herbivory or biological pest control. PMID- 26859497 TI - Assessing the eligibility of a non-invasive continuous blood pressure measurement technique for application during total intravenous anaesthesia. AB - OBJECTIVE: To assess the eligibility for replacement of invasive blood pressure as measured "within" the arterial vessel (IBP) with non-invasive continuous arterial blood pressure (cNIP) monitoring during total intravenous anaesthesia (TIVA), the ability of cNiP to track fast blood pressure changes needs to be quantified. A new method of statistical data analysis is developed for this purpose. METHODS: In a pilot study on patients undergoing neurosurgical anaesthesia, mean arterial pressure MAPIBP measured with IBP was compared to MAPCNP measured by the CNAP Monitor 500 in ten patients (age: 63+/-13 a). Correlation analysis of changes of device differences DeltaeMAP=DeltaMAPCNP DeltaMAPIBP with changes of MAPIBP (DeltaMAPIBP) during intervals of vasoactivity was conducted. An innovative technique, of linear trend analysis (LTA) applied to two signals, is described to perform this analysis without a priori knowledge of intervals of vasoactivity. RESULTS: Analysis of DeltaeMAP during vasoactivity revealed that DeltaMAPCNP systematically underestimated DeltaMAPIBP by 37%. This was confirmed in the complete data set using LTA technique showing a systematic, yet patient specific, underestimation in tracking DeltaMAPIBP (16...120%). CONCLUSION: The proposed LTA technique is able to detect systematic errors in tracking short-term blood pressure changes otherwise masked by established analysis. LTA may thus be a useful tool to assess the eligibility of cNIP to replace IBP during TIVA. PMID- 26859498 TI - Classification of persistent and long-standing persistent atrial fibrillation by means of surface electrocardiograms. AB - Atrial fibrillation, which is the most common cardiac arrhythmia, is typically classified into four clinical subtypes: paroxysmal, persistent, long-standing persistent and permanent. The ability to distinguish between them is of crucial significance in choosing the most suitable therapy for each patient. Nevertheless, classification is currently established once the natural history of the arrhythmia has been disclosed as it is not possible to make an early differentiation. This paper presents a novel method to discriminate persistent and long-standing atrial fibrillation patients by means of a time-frequency analysis of the surface electrocardiogram. Classification results provide approximately 75% accuracy when evaluating ECGs of consecutive unselected patients from a tertiary center and higher than 80% when patients are not under antiarrhythmic treatment or do not have structural heart disease (76% sensitivity and 88% specificity). Moreover, to our knowledge, this is the first study that discriminates between persistent and long-standing persistent subtypes in a heterogeneous population sample and without discontinuing antiarrhythmic therapy to patients. Thus, it can help clinicians to address the most suitable therapeutic approach for each patient. PMID- 26859499 TI - Kinins and microglial responses in bipolar disorder: a neuroinflammation hypothesis. AB - Bipolar disorder (BD) is a severe psychiatric disorder that affects up to 15% of the worldwide population. Characterized by switches in mood between mania and depression, its etiology is still unknown and efforts have been made to elucidate the mechanisms involved in first episode, development and progression of the disorder. Microglia activation, abnormal activity of GSK-3beta and reduction in neurotrophic factor expression related to neuroinflammatory processes have been indicated to be part of the disorder's pathophysiology. Lithium, the main mood stabilizer used for the treatment and prevention of relapses, acts as an anti inflammatory agent. Based on that, here we suggest a neuroinflammatory pathway for would be BD progression, in which microglia activation states modulated via constitutive induction of kinin-B1 receptor and reduction of kinin-B2 receptor expression and activity. PMID- 26859501 TI - Exploring the conformational heterogeneity of biomolecules: theory and experiments. PMID- 26859500 TI - Childhood Adversities and Adult Headache in Poland and Germany. AB - OBJECTIVE: Various childhood adversities have been found to be associated with chronic pain in adulthood. However, associations were moderate in most studies, i.e. odds ratios (OR) were between one and two. METHOD: An internet survey was performed in 508 Polish and 500 German subjects. A total of 19 childhood adversities were selected and their associations with headaches explored. Age, gender and country were included as potential confounders, as well as their two way interaction with the risk factors. RESULTS: Two strong risk factors were identified. (1) A combined score for physical and emotional neglect showed an odds ratio (OR) of 2.78 (p < .002) to the frequency of headache in adulthood as a main effect. (2) Father having had chronic pain showed an OR of 4.36 (p < .001) with headache in adulthood for women, but not for men (OR = 0.86, p < .556). The majority of the examined childhood adversities were not associated with adult headache, neither when tested individually nor as a sum score. CONCLUSION: This study confirms results from previous ones that childhood adversities may play a role in the development of adult headache, but it is a rather minor one. Contrary to other studies, neglect turned out to be one of the strongest predictors. PMID- 26859502 TI - Approach to haemangiomatosis causing congestive heart failure. AB - Haemangiomas represent the most common tumour of infancy. Although most cases are cutaneous benign lesions, multiple skin haemangiomas are associated with visceral involvement, especially of the liver. Hepatic haemangiomatosis may be complicated by high-output cardiac failure due to high-flow arteriovenous connections within the lesions. Different therapeutic strategies for treating haemangiomatosis causing heart failure include medical, surgical and interventional modalities. This study aimed to review the treatment options, discuss their benefits and flaws and propose a practical therapeutic approach for this medical situation. CONCLUSION: Our approach incorporates heart failure medications, dietary support and propranolol as first-line treatment, while corticosteroids, vincristine, percutaneous intervention and surgery are reserved for refractory cases. PMID- 26859503 TI - A comparison of tumour and host prognostic factors in screen-detected vs nonscreen-detected colorectal cancer: a contemporaneous study. AB - AIM: In addition to TNM stage there are adverse tumour and host factors, such as venous invasion and the presence of an elevated systemic inflammatory response (SIR), that influence the outcome in colorectal cancer. The present study aimed to examine how these factors varied in screen-detected (SD) and nonscreen detected (NSD) tumours. METHOD: Prospectively maintained databases of the prevalence round of a biennial population faecal occult blood test screening programme and a regional cancer audit database were analysed. Interval cancers (INT) were defined as cancers identified within 2 years of a negative screening test. RESULTS: Of the 395 097 people invited, 204 535 (52%) responded, 6159 (3%) tested positive and 421 (9%) had cancer detected. A further 708 NSD patients were identified [468 (65%) nonresponders, 182 (25%) INT cancers and 58 (10%) who did not attend or did not have cancer diagnosed at colonoscopy]. Comparing SD and NSD patients, SD patients were more likely to be male, and have a tumour with a lower TNM stage (both P < 0.05). On stage-by-stage analysis, SD patients had less evidence of an elevated SIR (P < 0.05). Both the presence of venous invasion (P = 0.761) and an elevated SIR (P = 0.059) were similar in those with INT cancers and in those that arose in nonresponders. CONCLUSION: Independent of TNM stage, SD tumours have more favourable host prognostic factors than NSD tumours. There is no evidence that INT cancers are biologically more aggressive than those that develop in the rest of the population and are hence likely to be due to limitations of screening in its current format. PMID- 26859504 TI - A case of sessile serrated adenoma/polyp observed with autofluorescence imaging. PMID- 26859505 TI - An extended simultaneous algebraic reconstruction technique (E-SART) for X-ray dual spectral computed tomography. AB - X-ray dual spectral computed tomography (DSCT) scans the measured object with two different x-ray energy spectra and the collected polychromatic projections from this procedure can be used to perform basis material decomposition of the object. An iterative method E-ART was recently proposed to produce highly quantitative basis material images for DSCT, but it has the drawback of slow convergence and huge computational costs. Inspired by the E-ART method, this paper proposes an extended simultaneous algebraic reconstruction technique (E-SART) for the basis material decomposition of DSCT and an accelerating strategy for improve the convergence speed of the iterative reconstruction. Compared with the E-ART method, the proposed method has much faster convergence rate while at the same time it has better noise suppressing feature. The advantages of this method were verified by experiments in which the FORBILD thorax phantom was iteratively reconstructed from noise-free and noisy polychromatic projections. SCANNING 38:599-611, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26859506 TI - An Appraisal of Inflammatory Markers in Distinguishing Acute Uncomplicated and Complicated Appendicitis. AB - BACKGROUND: It remains difficult to distinguish between complicated appendicitis (CAP) and uncomplicated appendicitis (UAP). There is a paucity of studies utilizing inflammatory markers to stratify the severity of acute appendicitis. This study aimed to evaluate and demonstrate the potential clinical utility of inflammatory markers as adjuncts in distinguishing CAP and UAP. METHODS: A comparative observational study was performed. Patients diagnosed with acute appendicitis were categorized as (a) complicated (necrosis, perforation, abscess) and (b) uncomplicated (inflamed, edematous). Hematological indices were combined to generate the following ratios: white cell lymphocyte ratio (WLR), white cell neutrophil ratio (WNR) and neutrophil lymphocyte ratio (NLR). Parameter accuracy was assessed using summary receiver operating characteristic (sROC) curves, classification and regression tree analysis and confusion matrix generation. RESULTS: On sROC analysis, neutrophils (area under the curve (AUC) 0.79, p < 0.001), WLR (AUC 0.79, p < 0.001) and NLR (AUC 0.79, p < 0.001) were the most accurate parameters in distinguishing CAP and UAP. White cell count (WCC; AUC 0.76, p < 0.001) and C-reactive protein (AUC 0.75, p < 0.001) were less accurate. WCC >12.25 (sensitivity 70%, specificity 68%) and NLR >5.47 (sensitivity 78%, specificity 70%) were the most accurate in identifying CAP. CONCLUSION: Inflammatory marker cutoff points can be generated and utilized to differentiate between UAP and CAP. This may be useful when deciding between conservative and operative management. PMID- 26859507 TI - Advances in the Management of Chemotherapy-Induced Nausea and Vomiting: New Data From Recent and Ongoing Trials. AB - Chemotherapy-induced nausea and vomiting (CINV) is among the most feared and debilitating adverse events experienced by cancer patients. Left unaddressed, CINV symptoms not only decrease quality of life, but may also affect patients' willingness to continue chemotherapy treatment. Detailed guidelines are available that outline best practices for prophylaxis of acute and delayed CINV. However, adherence to guideline recommendations continues to be suboptimal, and many patients still suffer unnecessarily from CINV. In addition, breakthrough/refractory CINV continues to present particular challenges. The development of effective CINV treatments with diverse mechanisms of action has expanded the options available for preventing symptoms. The US Food and Drug Administration has recently approved several new therapies for the management of CINV. NEPA is a fixed-dose combination of netupitant(300 mg) plus palonosetron (0.5 mg). In combination with dexamethasone, NEPA has demonstrated superior efficacyto palonosetron alone in patients receiving highly or moderately emetogenic chemotherapy. Rolapitant is a next generation neurokinin 1 (NK1) receptor antagonist. Both palonosetron and rolapitant have proven particularly effective in controlling delayed CINV. Regimens that combine a serotonin 5 hydroxytryptamine-3 receptor antagonist, an NK1receptor antagonist, and a corticosteroid now represent the standard of care for managing both acute and delayed CINV in patients receiving highly emetogenic chemotherapy. PMID- 26859511 TI - The Effect of Intra- and Intergenerational Caregiving on Subjective Well-Being- Evidence of a Population Based Longitudinal Study among Older Adults in Germany. AB - OBJECTIVE: To examine whether intra- and intergenerational caregiving affect subjective well-being (SWB) of the caregivers longitudinally. METHODS: Data were drawn from the German Ageing Survey (DEAS), which is a population-based longitudinal study of individuals living in Germany aged 40 and over. The waves in 2002, 2008 and 2011 were used (with 10,434 observations). SWB was examined in a broad sense, covering affective (AWB) and cognitive well-being (CWB), positive (PA) and negative affect (NA) as well as functional and mental health. While intragenerational caregiving was defined as providing care for spouse/partner, intergenerational caregiving was defined as providing care for mother, father, mother-in-law, father-in-law, partner's mother or partner's father. RESULTS: Fixed effects regressions adjusting for sociodemographic factors, social network, self-efficacy and morbidity showed that intergenerational informal care did not affect the various SWB outcome measures. Intragenerational caregiving affected CWB (women) and mental health (total sample and men), whereas it did not affect the other outcome variables. CONCLUSION: Our findings highlight the importance of intragenerational caregiving for mental health (men) and cognitive well-being (women). Consequently, interventions to avoid mental illness due to intragenerational caregiving are urgently needed. PMID- 26859512 TI - Binasal Prong versus Nasal Mask for Applying CPAP to Preterm Infants: A Randomized Controlled Trial. AB - BACKGROUND: Nasal continuous positive airway pressure (NCPAP) is being widely used for the treatment of respiratory distress syndrome (RDS) in preterm infants. However, there are only a few studies which compare different interfaces of NCPAP delivery and their effects on respiratory outcomes. OBJECTIVE: We aimed to determine whether NCPAP applied with binasal prongs compared to that with a nasal mask (NM) reduces the rate of moderate/severe bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: Infants between 26 and 32 weeks' gestation who suffered from RDS and were treated with NCPAP were assessed. Parallel randomization was performed to eligible infants to receive NCPAP either via binasal prongs or NM. Infants were intubated if they fulfilled the predefined failure criteria. Data were collected by using the intention-to-treat principle. RESULTS: One hundred and sixty infants were screened and 149 were randomized. Seventy-five infants in the binasal prong (NP) group and 74 in the NM group were analyzed. Mean gestational ages were 29.3 +/- 1.6 vs. 29.1 +/- 2.0 weeks (p = 0.55), and birth weights were 1,225 +/- 257 vs. 1,282 +/- 312 g (p = 0.22) in the NP and NM groups, respectively. The frequency of NCPAP failure within 24 h of life was higher in the NP than the NM group (8 vs. 0%; p = 0.09). The median duration of NCPAP was significantly higher in the NP group [median 4 (1-5) vs. 2 (1-3) h, p < 0.01]. The rate of moderate and severe BPD was significantly lower in the NM (n = 2, 2.7%) when compared with the NP group (n = 11, 14.6%; p < 0.01). The BPD/death rates were not different between the 2 groups (NM group: n = 18 or 24.3%; NP group: n = 19 or 25.3%; p = 0.51). CONCLUSIONS: The NM was successfully used for delivering NCPAP in preterm infants, and no NCPAP failure was observed within the first 24 h. These data show that applying NCPAP by NM yielded a shorter duration of NCPAP and statistically reduced the rates of moderate and severe BPD. PMID- 26859513 TI - Controlled Formation of Surface Patterns in Metal Films Deposited on Elasticity Gradient PDMS Substrates. AB - Controlled surface patterns are useful in a wide range of applications including flexible electronics, elastomeric optics, fluidic channels, surface engineering, measurement technique, biological templates, stamps, and sensors. In this work, we report on the controlled formation of surface patterns in metal films deposited on elasticity-gradient polydimethylsiloxane (PDMS) substrates. Because of the temperature gradient during the curing process, the PDMS substrate in each sample successively changes from a purely liquid state at one side to a purely elastic state at the opposite side. It is found that surface folds appear in the liquid or viscous PDMS region while wrinkles form in the elastic region. In the transition region from the liquid to elastic PDMS, a nested pattern (i.e., the coexisting of folds and wrinkles) can be observed. The folding wave is triggered by the intrinsic stress during the film deposition and its wavelength is independent of the film thickness. The wrinkling wave is induced by the thermal compression after deposition and its wavelength is proportional to the film thickness. The report in this work could promote better understanding of the effect of substrate elasticity on the surface patterns and fabrication of such patterns (folds and wrinkles) by tuning the substrate property. PMID- 26859515 TI - High-Performanced Cathode with a Two-Layered R-P Structure for Intermediate Temperature Solid Oxide Fuel Cells. AB - Driven by the mounting concerns on global warming and energy crisis, intermediate temperature solid-oxide fuel cells (IT-SOFCs) have attracted special attention for their high fuel efficiency, low toxic gas emission, and great fuel flexibility. A key obstacle to the practical operation of IT-SOFCs is their sluggish oxygen reduction reaction (ORR) kinetics. In this work, we applied a new two-layered Ruddlesden-Popper (R-P) oxide, Sr3Fe2O7-delta (SFO), as the material for oxygen ion conducting IT-SOFCs. Density functional theory calculation suggested that SFO has extremely low oxygen ion formation energy and considerable energy barrier for O(2-) diffusion. Unfortunately, the stable SrO surface of SFO was demonstrated to be inert to O2 adsorption and dissociation reaction, and thus restricts its catalytic activity toward ORR. Based on this observation, Co partially substituted SFO (SFCO) was then synthesized and applied to improve its surface vacancy concentration to accelerate the oxygen adsorptive reduction reaction rate. Electrochemical performance results suggested that the cell using the SFCO single phase cathode has a peak power density of 685 mW cm(-2) at 650 degrees C, about 15% higher than those when using LSCF cathode. Operating at 200 mA cm(-2), the new cell using SFCO is quite stable within the 100-h' test. PMID- 26859516 TI - The ratio of metabolically active versus total Mycolata populations triggers foaming in a membrane bioreactor. AB - The abundance of total and metabolically active populations of Mycolata was evaluated in a full-scale membrane bioreactor (MBR) experiencing seasonal foaming, using quantitative PCR (qPCR) and retrotranscribed qPCR (RT-qPCR) targeting the 16S rRNA gene sequence. While the abundance of total Mycolata remained stable (10(10) copies of 16S rRNA genes/L activated sludge) throughout four different experimental phases, significant variations (up to one order of magnitude) were observed when the 16S rRNA was targeted. The highest ratios of metabolically active versus total Mycolata populations were observed in samples of two experimental phases when foaming was experienced in the MBR. Non-metric multidimensional scaling and BIO-ENV analyses demonstrated that this ratio was positively correlated to the concentrations of substrates in the influent water, F/M ratio, and pH, and negatively correlated to temperature and solids retention time. It the first time that the ratio of metabolically active versus total Mycolata is found to be a key parameter triggering foaming in the MBR; thus, we propose it as a candidate predictive tool. PMID- 26859517 TI - Robust Nanoparticle-DNA Conjugates Based on Mussel-Inspired Polydopamine Coating for Cell Imaging and Tailored Self-Assembly. AB - We have demonstrated that mussel-inspired polydopamine can serve as an intermediate coating layer for covalently attaching oligonucleotides on nanostructures of diverse chemical nature, which are made possible by the universal adhesion and spontaneous reactivity of polydopamine. Our results have shown that polydopamine can strongly bond to representative nanoparticles (i.e., Au nanoparticles and magnetic polymer nanobeads) and form a thin layer of coating that allows for attachment of commercially available DNA with thiol or amine end functionality. The resulting DNA-nanoparticle conjugates not only show excellent chemical and thermal stability and high loading density of DNA, but the linked DNA also maintain their biological functions in directing cancer cell targeting and undergo DNA hybridization to form multifunctional magnetic core-plasmonic satellite assemblies. The generally applicable strategy opens new opportunities for easy adoption of DNA-nanoparticle conjugates for broad applications in biosensors and nanomedicine. PMID- 26859518 TI - Contrasting single and multi-component working-memory systems in dual tasking. AB - Working memory can be a major source of interference in dual tasking. However, there is no consensus on whether this interference is the result of a single working memory bottleneck, or of interactions between different working memory components that together form a complete working-memory system. We report a behavioral and an fMRI dataset in which working memory requirements are manipulated during multitasking. We show that a computational cognitive model that assumes a distributed version of working memory accounts for both behavioral and neuroimaging data better than a model that takes a more centralized approach. The model's working memory consists of an attentional focus, declarative memory, and a subvocalized rehearsal mechanism. Thus, the data and model favor an account where working memory interference in dual tasking is the result of interactions between different resources that together form a working-memory system. PMID- 26859491 TI - Low Ambient Temperature and Intracerebral Hemorrhage: The INTERACT2 Study. AB - BACKGROUND: Rates of acute intracerebral hemorrhage (ICH) increase in winter months but the magnitude of risk is unknown. We aimed to quantify the association of ambient temperature with the risk of ICH in the Intensive Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT2) participants on an hourly timescale. METHODS: INTERACT2 was an international, open, blinded endpoint, randomized controlled trial of patients with spontaneous ICH (<6h of onset) and elevated systolic blood pressure (SBP, 150-220 mmHg) assigned to intensive (target SBP <140 mmHg) or guideline-recommended (SBP <180 mmHg) BP treatment. We linked individual level hourly temperature to baseline data of 1997 participants, and performed case-crossover analyses using a distributed lag non linear model with 24h lag period to assess the association of ambient temperature and risk of ICH. Results were presented as overall cumulative odds ratios (ORs) and 95% CI. RESULTS: Low ambient temperature (<=10 degrees C) was associated with increased risks of ICH: overall cumulative OR was 1.37 (0.99-1.91) for 10 degrees C, 1.92 (1.31-2.81) for 0 degrees C, 3.13 (1.89-5.19) for -10 degrees C, and 5.76 (2.30-14.42) for -20 degrees C, as compared with a reference temperature of 20 degrees C.There was no clear relation of low temperature beyond three hours after exposure. Results were consistent in sensitivity analyses. CONCLUSIONS: Exposure to low ambient temperature within several hours increases the risk of ICH. TRIAL REGISTRATION: ClinicalTrials.gov NCT00716079. PMID- 26859514 TI - Muscle atrophy in patients with Type 2 Diabetes Mellitus: roles of inflammatory pathways, physical activity and exercise. AB - Muscle atrophy is caused by an imbalance in contractile protein synthesis and degradation which can be triggered by various conditions including Type 2 Diabetes Mellitus (T2DM). Reduced muscle quality in patients with T2DM adversely affects muscle function, the capacity to perform activities of daily living, quality of life and ultimately may increase the risk of premature mortality. Systemic inflammation initiated by obesity and prolonged overnutrition not only contributes to insulin resistance typical of T2DM, but also promotes muscle atrophy via decreased muscle protein synthesis and increased ubiquitin proteasome, lysosomal-proteasome and caspase 3- mediated protein degradation. Emerging evidence suggests that the inflammation-sensitive Nuclear Factor kappa B (NF-kappaB) and Signal Transducer and Activator of Transcription 3 (STAT3) pathways may contribute to muscle atrophy in T2DM. In contrast, exercise appears to be an effective tool in promoting muscle hypertrophy, in part due to its effect on systemic and local (skeletal muscle) inflammation. The current review discusses the role inflammation plays in muscle atrophy in T2DM and the role of exercise training in minimising the effect of inflammatory markers on skeletal muscle. We also report original data from a cohort of obese patients with T2DM compared to age-matched controls and demonstrate that patients with T2DM have 60% higher skeletal muscle expression of the atrophy transcription factor FoxO1. This review concludes that inflammatory pathways in muscle, in particular, NF-kappaB, potentially contribute to T2DM-mediated muscle atrophy. Further in-vivo and longitudinal human research is required to better understand the role of inflammation in T2DM-mediated atrophy and the anti-inflammatory effect of exercise training under these conditions. PMID- 26859519 TI - Proactive inhibitory control: A general biasing account. AB - Flexible behavior requires a control system that can inhibit actions in response to changes in the environment. Recent studies suggest that people proactively adjust response parameters in anticipation of a stop signal. In three experiments, we tested the hypothesis that proactive inhibitory control involves adjusting both attentional and response settings, and we explored the relationship with other forms of proactive and anticipatory control. Subjects responded to the color of a stimulus. On some trials, an extra signal occurred. The response to this signal depended on the task context subjects were in: in the 'ignore' context, they ignored it; in the 'stop' context, they had to withhold their response; and in the 'double-response' context, they had to execute a secondary response. An analysis of event-related brain potentials for no-signal trials in the stop context revealed that proactive inhibitory control works by biasing the settings of lower-level systems that are involved in stimulus detection, action selection, and action execution. Furthermore, subjects made similar adjustments in the double-response and stop-signal contexts, indicating an overlap between various forms of proactive action control. The results of Experiment 1 also suggest an overlap between proactive inhibitory control and preparatory control in task-switching studies: both require reconfiguration of task-set parameters to bias or alter subordinate processes. We conclude that much of the top-down control in response inhibition tasks takes place before the inhibition signal is presented. PMID- 26859522 TI - Unexpected Scholl Reaction of 6,7,13,14-Tetraarylbenzo[k]tetraphene: Selective Formation of Five-Membered Rings in Polycyclic Aromatic Hydrocarbons. AB - Cyclodehydrogenation is a versatile reaction that has enabled the syntheses of numerous polycyclic aromatic hydrocarbons (PAHs). We now describe a unique Scholl reaction of 6,7,13,14-tetraarylbenzo[k]tetraphene, which "unexpectedly" forms five-membered rings accompanying highly selective 1,2-shift of aryl groups. The geometric and optoelectronic nature of the resulting bistetracene analogue with five-membered rings is comprehensively investigated by single-crystal X-ray, NMR, UV-vis absorption, and cyclic voltammetry analyses. Furthermore, a possible mechanism is proposed to account for the selective five-membered-ring formation with the rearrangement of the aryl groups, which can be rationalized by density functional theory (DFT) calculations. The theoretical results suggest that the formation of the bistetracene analogue with five-membered rings is kinetically controlled while an "expected" product with six-membered rings is thermodynamically more favored. These experimental and theoretical results provide further insights into the still controversial mechanism of the Scholl reaction as well as open up an unprecedented entry to extend the variety of PAHs by programing otherwise unpredictable rearrangements during the Scholl reaction. PMID- 26859520 TI - Metabolomics study on the antitumor effect of marine natural compound flexibilide in HCT-116 colon cancer cell line. AB - A marine natural compound flexibilide isolated from the soft coral Sinularia flexibilis has been found to have antitumor activity. However, its pharmacological mechanism on tumor cells has not been studied. Herein, an ultra performance liquid chromatography coupled to quadrupole time of-flight mass spectrometry (UPLC/Q-TOF MS) based metabolomics approach was established to investigate the antitumor effect of flexibilide on HCT-116 cells and its action mechanism. Q-TOF MS and MS/MS were used to identify significantly different metabolites. Comparing flexibilide-treated HCT-116 cells group with control group (dimethyl sulfoxide), 19 distinct metabolites involved in sphingolipid metabolism, alanine, aspartate and glutamate metabolism, d-glutamine and d glutamate metabolism, glycerophospholipid metabolism, pyrimidine metabolism and others were discovered and identified. The significant decrease of phosphatidylcholine (PC) and phosphocholine levels and increase of lysophosphatidylcholine (LysoPC) levels in flexibilide treated cells suggested down-regulation of PC biosynthesis pathway. The decrease of sphingolipids reflected the lesions of cell membrane, and the up-regulation of sphingosine-1 phosphate indicated that TRAF2 and caspase-8 were likely to be activated by flexibilide and further caused cell apoptosis. Furthermore, TCA cycle was deemed to be down-regulated after flexibilide treatment, which might lead to an unsustainable of mitochondrial transmembrane potential MMP). The further measured descreased MMP with the increasing concentration of flexibilide treatment indiciated the dysfunction of mitochondrial which might finally lead to apoptosis. The UPLC/Q-TOF MS based metabolomics approach provides new insights into the mechanistic studies of flexibilide on tumor cells, which benefit its further improvement and application. PMID- 26859523 TI - The hallucinogenic diterpene salvinorin A inhibits leukotriene synthesis in experimental models of inflammation. AB - Leukotrienes (LTs) are lipid mediators derived from arachidonic acid (AA) involved in a number of autoimmune/inflammatory disorders including asthma, allergic rhinitis and cardiovascular diseases. Salvinorin A (SA), a diterpene isolated from the hallucinogenic plant Salvia divinorum, is a well-established analgesic compound, but its anti-inflammatory properties are under-researched and its effects on LT production is unknown to date. Here, we studied the possible effect of SA on LT production and verified its actions on experimental models of inflammation in which LTs play a prominent role. Peritoneal macrophages (PM) stimulated by calcium ionophore A23187 were chosen as in vitro system to evaluate the effect of SA on LT production. Zymosan-induced peritonitis in mice and carrageenan-induced pleurisy in rats were selected as LT-related models to evaluate the effect of SA on inflammation as well as on LT biosynthesis. SA inhibited, in a concentration-dependent manner, A23187-induced LTB4 biosynthesis in isolated PM. In zymosan-induced peritonitis, SA inhibited cell infiltration, myeloperoxidase activity, vascular permeability and LTC4 production in the peritoneal cavity without decreasing the production of prostaglandin E2. In carrageenan-induced pleurisy in rats, a more sophisticated model of acute inflammation related to LTs, SA significantly inhibited LTB4 production in the inflammatory exudates, along with reducing the phlogistic process in the lung. In conclusion, SA inhibited LT production and it was effective in experimental models of inflammation in which LTs play a pivotal role. SA might be considered as a lead compound for the development of drugs useful in LTs-related diseases. PMID- 26859521 TI - Climate change impact on the PAH photodegradation in soils: Characterization and metabolites identification. AB - Polycyclic aromatic hydrocarbons (PAHs) are airborne pollutants that are deposited on soils. As climate change is already altering temperature and solar radiation, the global warming is suggested to impact the environmental fate of PAHs. This study was aimed at evaluating the effect of climate change on the PAH photodegradation in soils. Samples of Mediterranean soils were subjected to different temperature and light radiation conditions in a climate chamber. Two climate scenarios were considered according to IPCC projections: 1) a base (B) scenario, being temperature and light intensity 20 degrees C and 9.6W/m(2), respectively, and 2) a climate change (CC) scenario, working at 24 degrees C and 24W/m(2), respectively. As expected, low molecular weight PAHs were rapidly volatilized when increasing both temperature and light intensity. In contrast, medium and high molecular weight PAHs presented different photodegradation rates in soils with different texture, which was likely related to the amount of photocatalysts contained in both soils. In turn, the hydrogen isotopic composition of some of the PAHs under study was also investigated to verify any degradation process. Hydrogen isotopes confirmed that benzo(a)pyrene is degraded in both B and CC scenarios, not only under light but also in the darkness, revealing unknown degradation processes occurring when light is lacking. Potential generation pathways of PAH photodegradation by-products were also suggested, being a higher number of metabolites formed in the CC scenario. Consequently, in a more or less near future, although humans might be less exposed to PAHs, they could be exposed to new metabolites of these pollutants, which might be even more toxic. PMID- 26859524 TI - Effects of partial vascular occlusion on irisin responses to loaded muscle contractions. AB - The purpose of the study was to determine the effects of partial vascular occlusion on irisin responses. Eight males completed trials of light (30% 1 repetition maximum (1RM)) resistance exercise (single biceps curls and calf presses) with partial vascular occlusion (LRO), moderate resistance (70% 1RM) with no occlusion (MR), and occlusion only (OO). Blood was collected before, after, and 15 min after exercise. Changes in circulating irisin were more affected during LRO than MR and OO trials. PMID- 26859525 TI - The influence of the dorsolateral prefrontal cortex on attentional behavior and decision making. A t-DCS study on emotionally vs. functionally designed objects. AB - Prior research has shown that right dorsolateral prefrontal cortex may be crucial in cognitive control of affective impulses during decision making. The present study examines whether modulation of r-DLPFC with transcranial direct current stimulation influences attentional behavior and decision-making in a purchase task requiring participants to choose either emotional/attractive or functional/useful objects. 30 participants were shown sixteen pairs of emotionally or functionally designed products while their eye-movements were recorded. Participants were asked to judge aesthetics and usefulness of each object, and to decide which object of each pair they would buy. Results revealed that participants decided to buy the functionally designed objects more often regardless of condition; however, participants receiving anodal stimulation were faster in decision making. Although stimulation of r-DLPFC did not affect the actual purchasing choice and had little effect on visual exploration during decision making, it influenced perceived usefulness and attractiveness, with temporary inhibition of r-DLPFC leading to evaluate functional objects as less attractive. Finally, anodal stimulation led to judge the objects as more useful. The implications of these results are discussed. PMID- 26859526 TI - Collaborative Total Synthesis: Routes to (+/-)-Hippolachnin A Enabled by Quadricyclane Cycloaddition and Late-Stage C-H Oxidation. AB - Described herein are synthetic efforts toward the synthesis of hippolachnin A. Two independently devised routes from the Brown and Wood groups allowed for the synthesis of hippolachnin A from the unusual starting material, quadricyclane, by harnessing the power of late-stage C-H oxidation. Collaborative union of the best features of the two routes allowed for preparation of the molecule with improved efficiency. PMID- 26859527 TI - van der Waals Heterostructures with High Accuracy Rotational Alignment. AB - We describe the realization of van der Waals (vdW) heterostructures with accurate rotational alignment of individual layer crystal axes. We illustrate the approach by demonstrating a Bernal-stacked bilayer graphene formed using successive transfers of monolayer graphene flakes. The Raman spectra of this artificial bilayer graphene possess a wide 2D band, which is best fit by four Lorentzians, consistent with Bernal stacking. Scanning tunneling microscopy reveals no moire pattern on the artificial bilayer graphene, and tunneling spectroscopy as a function of gate voltage reveals a constant density of states, also in agreement with Bernal stacking. In addition, electron transport probed in dual-gated samples reveals a band gap opening as a function of transverse electric field. To illustrate the applicability of this technique to realize vdW heterostructuctures in which the functionality is critically dependent on rotational alignment, we demonstrate resonant tunneling double bilayer graphene heterostructures separated by hexagonal boron-nitride dielectric. PMID- 26859528 TI - Ketogenic diet and other dietary treatments for epilepsy. AB - BACKGROUND: The ketogenic diet (KD), being high in fat and low in carbohydrates, has been suggested to reduce seizure frequency. It is currently used mainly for children who continue to have seizures despite treatment with antiepileptic drugs. Recently, there has been interest in less restrictive KDs including the modified Atkins diet (MAD) and the use of these diets has extended into adult practice. OBJECTIVES: To review the evidence for efficacy and tolerability from randomised controlled trials regarding the effects of KD and similar diets. SEARCH METHODS: We searched the Cochrane Epilepsy Group's Specialized Register (30 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online (CRSO, 30 March 2015), MEDLINE (Ovid, 30 March 2015), ClinicalTrials.gov (30 March 2015) and the WHO International Clinical Trials Registry Platform (ICTRP, 30 March 2015). We imposed no language restrictions. We checked the reference lists of retrieved studies for additional reports of relevant studies. SELECTION CRITERIA: Studies of KDs and similar diets for people with epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently applied pre-defined criteria to extract data and assessed study quality. MAIN RESULTS: We identified seven randomised controlled trials that generated eight publications.All trials applied an intention-to-treat analysis with varied randomisation methods. The seven studies recruited 427 children and adolescents and no adults. We could not conduct a meta-analysis due to the heterogeneity of the studies.Reported rates of seizure freedom reached as high as 55% in a 4 : 1 KD group after three months and reported rates of seizure reduction reached as high as 85% in a 4 : 1 KD group after three months.One trial found no significant difference between the fasting-onset and gradual-onset KD for rates of seizure freedom and reported a greater rate of seizure reduction in the gradual-onset KD group.Studies assessing the efficacy of the MAD reported seizure freedom rates of up to 10% and seizure reduction rates of up to 60%. One study compared the MAD to a 4 : 1 KD, but did not report rates of seizure freedom or seizure reduction.Adverse effects were fairly consistent across different dietary interventions. The most commonly reported adverse effects were gastrointestinal syndromes. It was common that adverse effects were the reason for participants dropping out of trials. Other reasons for drop-out included lack of efficacy and non-acceptance of the diet.Although there was some evidence for greater antiepileptic efficacy for a 4 : 1 KD over lower ratios, the 4 : 1 KD was consistently associated with more adverse effects.No studies assessed the effect of dietary interventions on quality of life, or cognitive or behavioural functioning. AUTHORS' CONCLUSIONS: The randomised controlled trials discussed in this review show promising results for the use of KDs in epilepsy. However, the limited number of studies, small sample sizes and a sole paediatric population resulted in a poor overall quality of evidence.There were adverse effects within all of the studies and for all KD variations, such as short-term gastrointestinal related disturbances, to longer-term cardiovascular complications. Attrition rates remained a problem with all KDs and across all studies, reasons for this being lack of observed efficacy and dietary tolerance.There was a lack of evidence to support the clinical use of KD in adults with epilepsy, therefore, further research would be of benefit.Other more palatable but related diets, such as the MAD ketogenic diet, may have a similar effect on seizure control as classical KD but this assumption requires more investigation. For people who have medically intractable epilepsy or people who are not suitable for surgical intervention, a KD remains a valid option; however, further research is required. PMID- 26859529 TI - Evaluating Ureteral Wall Injuries with Endoscopic Grading System and Analysis of the Predisposing Factors. AB - OBJECTIVE: To analyze the predictive factors for intraoperative ureteral wall injury due to semirigid ureteroscopy (URS) used in the treatment of ureteral calculi. METHODS: The data of 437 patients who had URS due to ureteral stones were prospectively analyzed. The ureteral wall injuries that occurred during URS were reviewed endoscopically at the end of surgery and divided into two groups as low grade (grades 0 and 1) and high grade (grades 2, 3, and 4) according to classification of ureteral wall injuries. Those two groups were compared for patient and stone characteristics and perioperative findings. RESULTS: Ureteral wall injury was seen in 133 (30.4%) patients after surgery. According to the endoscopic classification of the lesions after URS, grades 0, 1, 2, and 3 injury were seen in 69.5%, 16.4%, 11.2%, and 2.7% of the patients, respectively. There were no grade 4 injuries in our series. Two groups showed statistically significant differences for the location (prox- vs distal and mid-ureter) and size of the stone (9.9 mm vs 14.03 mm), presence of preoperatively urinary tract infection (UTI) (12% vs 50.8%), needed balloon dilatation (9.8% vs 36.1%), duration of surgery (33.6 min vs 43.3 min), and surgical success rate (90% vs 76%) (p = 0.01, for all). Stone size, location, duration of surgery, and presence of preoperative infection were determined as independent prognostic factors for mucosal injury. CONCLUSION: The ureteral wall injury grading system may be used for standardized reporting of ureteral lesions after ureteroscopy. Big, proximal ureteral stone, longer operation time, and presence of UTI are the risk factors for ureteral wall injury during URS. PMID- 26859531 TI - A Procedure-Spanning Analysis of Plasma Membrane Integrity for Assessment of Cell Viability in Sperm Cryopreservation of Zebrafish Danio rerio. AB - The goal of this study was to evaluate plasma membrane integrity and motility for zebrafish sperm quality assessment along the cryopreservation pathway-from sample collection through refrigerated storage, cryoprotectant equilibration, freezing, thawing, and fertilization. The objectives were to: (1) evaluate the effects of osmolality, extender, and refrigerated storage on sperm plasma membrane integrity and motility, and (2) compare cryopreservation of sperm from farm-raised and well characterized research populations by evaluating motility and membrane integrity of fresh, post-equilibration (before freezing) and post-thaw sperm, and post-thaw fertility. Osmolality, extender, and storage time each influenced sperm motility and membrane integrity. Isotonic osmolality showed the best protection for motility and membrane integrity compared to hypotonic and hypertonic osmolalities. Of the four tested extenders, Hanks' balanced salt solution (HBSS) and Ca(2+)-free HBSS showed the best protection compared with NaCl and glucose, and sperm retained motility and membrane integrity for 24 h of refrigerated storage. Sperm cryopreservation of zebrafish from a farm population (n = 20) and an AB research line (n = 20) showed significant differences in post-thaw fertility (32% +/- 18% vs. 73% +/- 21%). No differences were found in post-thaw motility, although the farm-raised zebrafish possessed a larger body size, testis weight, and higher fresh motility. Correlation analysis of pooled data did not identify correlations among motility, flow cytometry analysis of membrane integrity and recognizable cells, and post-thaw sperm fertility (p >= 0.202). More research is needed to standardize the fertilization conditions especially sperm-to-egg ratio to avoid possible overabundance of sperm to obscure the differences. PMID- 26859532 TI - Three-Dimensional Model for Electrospinning Processes in Controlled Gas Counterflow. AB - We study the effects of a controlled gas flow on the dynamics of electrified jets in the electrospinning process. The main idea is to model the air drag effects of the gas flow by using a nonlinear Langevin-like approach. The model is employed to investigate the dynamics of electrified polymer jets at different conditions of air drag force, showing that a controlled gas counterflow can lead to a decrease of the average diameter of electrospun fibers, and potentially to an improvement of the quality of electrospun products. We probe the influence of air drag effects on the bending instabilities of the jet and on its angular fluctuations during the process. The insights provided by this study might prove useful for the design of future electrospinning experiments and polymer nanofiber materials. PMID- 26859533 TI - Particulate Matter Exposure and Cardiopulmonary Differences in the Multi-Ethnic Study of Atherosclerosis. AB - BACKGROUND: Particulate matter (PM) exposure may directly affect the pulmonary vasculature. Although the pulmonary vasculature is not easily measurable, differential associations for right ventricular (RV) and left ventricular (LV) mass may provide an indirect assessment of pulmonary vascular damage. OBJECTIVES: We tested whether long-term exposure to PM < 2.5 MUm (PM2.5) is associated with greater RV mass and RV mass/end-diastolic volume ratio relative to the LV. METHODS: The Multi-Ethnic Study of Atherosclerosis performed cardiac magnetic resonance (CMR) imaging among participants 45-84 years old without clinical cardiovascular disease in 2000-2002 in six U.S. cities. A fine-scale spatiotemporal model estimated ambient PM2.5 exposure in the year before CMR; individually weighted estimates accounted for indoor exposure to ambient PM2.5. Linear regression models were adjusted for demographics, anthropometrics, smoking status, cardiac risk factors, and LV parameters, with additional adjustment for city. RESULTS: The 4,041 included participants had a mean age of 61.5 years, and 47% were never smokers. The mean ambient PM2.5 was 16.4 MUg/m3 and individually weighted PM2.5 was 11.0 MUg/m3. PM2.5 exposure was associated with greater RV mass [ambient: 0.11 g per 5 MUg/m3 (95% CI: -0.05, 0.27); individually weighted: 0.20 g per 5 MUg/m3 (95% CI: 0.04, 0.36)] and a greater RV mass/end-diastolic volume ratio conditional on LV parameters. City-adjusted results for RV mass were of greater magnitude and were statistically significant for both measures of PM2.5, whereas those for RV mass/end-diastolic volume ratio were attenuated. CONCLUSIONS: Long-term PM2.5 exposures were associated with greater RV mass and RV mass/end-diastolic volume ratio conditional on the LV; however, additional adjustment for city attenuated the RV mass/end-diastolic volume findings. These findings suggest that PM2.5 exposure may be associated with subclinical cardiopulmonary differences in this general population sample. CITATION: Aaron CP, Chervona Y, Kawut SM, Diez Roux AV, Shen M, Bluemke DA, Van Hee VC, Kaufman JD, Barr RG. 2016. Particulate matter exposure and cardiopulmonary differences in the Multi-Ethnic Study of Atherosclerosis. Environ Health Perspect 124:1166-1173; http://dx.doi.org/10.1289/ehp.1409451. PMID- 26859535 TI - Screening History Among Women with Invasive Cervical Cancer in an Academic Medical Center: Will We Miss Cancers Following Updated Guidelines? AB - OBJECTIVE: Updated guidelines for the screening and management of cervical cancer in the United States recommend starting Papanicolaou (Pap) testing at age 21 and screening less frequently with less aggressive management for abnormalities. We sought to examine updated Pap test screening guidelines and how they may affect the detection of invasive cervical cancer, especially among women <30 years of age. MATERIALS AND METHODS: Patients diagnosed at Brigham and Women's Hospital with invasive cervical cancer between 2002 and 2012 were retrospectively identified. Prior screening history was obtained and patients were divided into two groups based on age <30 years or age >=30 years. The two groups were then compared with respect to demographics, pathological findings, and time to diagnosis. RESULTS: A total of 288 patients with invasive cervical carcinoma were identified. Among these patients, 109 had adequate information on prior screening history. Invasive adenocarcinoma (IAC) was diagnosed in 37 (33.94%) patients, whereas 64 (58.72%) patients were diagnosed with invasive squamous cell carcinoma (ISCC). The remaining eight patients were diagnosed with other types of cancers of the cervix. A total of 13 patients were younger than 30 while 96 patients were 30 or older. The mean time from normal Pap to diagnosis of IAC was 15 months in patients younger than 30 years of age compared to 56 months in patients aged 30 and older (p < 0.001). The mean time from normal Pap to diagnosis of ISCC was 38 months in patients younger than 30 years of age and 82 months in patients aged 30 and older (p = 0.018). CONCLUSION: In this small retrospective study, updated Pap test screening guidelines would not have missed invasive cancer on average among screened women age 30 and older. However, young patients aged 21-29 years may be at increased risk of developing IAC of the cervix between the recommended screening intervals. PMID- 26859536 TI - Modeling Growth Kinetic Parameters of Salmonella Enteritidis SE86 on Homemade Mayonnaise Under Isothermal and Nonisothermal Conditions. AB - During the last decade, a specific strain of Salmonella Enteritidis (named SE86) has been identified as the major etiological agent responsible for salmonellosis in the State of Rio Grande do Sul, Southern Brazil, and the main food vehicle was homemade mayonnaise (HM). This study aimed to model the growth prediction of SE86 on HM under isothermal and nonisothermal conditions. SE86 was inoculated on HM and stored at 7, 10, 15, 20, 25, 30, and 37 degrees C. Growth curves were built by fitting data to the Baranyi's DMFit, generating r(2) values greater than 0.98 for primary models. Secondary model was fitted with Ratkowsky equation, generating r(2) and root mean square error values of 0.99 and 0.016, respectively. Also, the growth of SE86 under nonisothermal conditions simulating abuse temperature during preparation, storage, and serving of HM was studied. Experimental data showed that SE86 did not grow on HM at 7 degrees C for 30 days. At 10 degrees C, no growth was observed until approximately 18 h, and the infective dose (assumed as 10(6) CFU/g) was reached after 8.1 days. However, the same numbers of SE86 were attained after 6 hours at 37 degrees C. Experimental data demonstrated shorter lag times than those generated by ComBase Predictive Models, suggesting that SE86 is very well adapted for growing on HM. SE86 stored under nonisothermal conditions increased population to reach about 10(6) CFU/g after approximately 30 hours of storage. In conclusion, the developed model can be used to predict the growth of SE86 on HM under various temperatures, and considering this pathogen, HM can be produced if safe eggs are used and HM is stored below 7 degrees C. PMID- 26859534 TI - Comparing Readmissions and Infectious Complications of Blunt Splenic Injuries Using a Statewide Database. AB - BACKGROUND: Although non-operative management of blunt splenic injury (BSI) is increasingly common, the long-term infectious complications after adjunct splenic artery embolization (SAE) are not well described. METHODS: Patients aged 18-64 y with BSI were identified in the California State Inpatient Database (2007-2011) and categorized as receiving either non-operative management (NOM) without SAE, NOM with SAE, or operative management (OM). The cumulative incidence of infections (surgical site infections [SSI], pneumonia, urinary tract infections, and sepsis) requiring readmission at different times up to one y after injury were calculated. Patient and treatment factors associated with infectious readmissions were determined using multivariable logistic regression models. RESULTS: Of the 4,360 patients with BSI, 61.6% had NOM without SAE, 5.8% had NOM with SAE, and 32.6% had OM. The cumulative incidences of infectious complications after each of the management modes were 1.27%, 1.59%, and 1.76%, respectively, during admission (p = 0.446); 2.16%, 5.18%, and 4.85%, respectively, at 30 d after injury (p < 0.001); and 4.69%, 9.16%, and 8.85%, respectively, at one y after injury (p < 0.001). Risk factors for infection-associated readmissions within one y after injury were Charlson score >=2 (adjusted odds ratio [AOR] 3.9; 95% confidence interval [CI] 2.61-6.02), length of stay >seven d (AOR 2.47; 95% CI 1.58-3.85), NOM with SAE (AOR 2.00; 95% CI 1.19-3.34), and OM (AOR 1.47; 95% CI 1.05-2.07). CONCLUSIONS: The long-term risk of infectious complications in patients with BSI who have NOM with SAE is similar to that in patients who are treated with OM, indicating the need for pro-active strategies to reduce long term infectious complications after SAE. PMID- 26859537 TI - The Case for Telemental Health for Improving the Accessibility and Quality of Children's Mental Health Services. AB - OBJECTIVE: Children's mental health problems collectively impose a staggering public health burden. However, the quality of regionally accessible children's mental healthcare varies greatly, with youth in rural and other remote communities particularly underserved. Promoting knowledge and skill in telemental health (TMH) is critical to meaningfully overcoming traditional geographic barriers to children's mental healthcare. METHODS: To introduce this special section, we review the increasing need for child and adolescent mental health services, the decreasing child mental health workforce, and the role that TMH can play in new models of care. RESULTS: Authors in this special edition are experienced TMH innovators and providers, and offer expert perspectives on the current and evolving status of TMH practice in child and adolescent mental health. The articles in this collection draw on leading TMH examples, using a range of interventions implemented across diverse TMH settings, to systematically address the critical technical, ethical, regulatory, clinical, and service delivery aspects of TMH care. These articles strategically outline the key considerations requisite for effectively incorporating TMH into children's mental healthcare Conclusions: TMH is a rapidly developing service delivery model that is already beginning to innovate systems of care to meet the expanding mental healthcare needs of the nation's children. PMID- 26859538 TI - Pharmacodynamics and Pharmacokinetics Following Once-Daily and Twice-Daily Dosing of Tiotropium Respimat(r) in Asthma Using Standardized Sample-Contamination Avoidance. AB - BACKGROUND: This study was conducted to confirm the 24-hour bronchodilator efficacy and pharmacokinetic profile of once-daily tiotropium Respimat(r) 5 MUg add-on to inhaled corticosteroids (ICS) in adults with symptomatic asthma. It used a trial protocol designed to minimize the risk of pharmacokinetic sample contamination resulting from improper sampling procedure, sample handling, or device handling during priming and subsequent inhalation procedure. METHODS: A Phase II, randomized, double-blind, two-way crossover study (NCT01696071) comparing two daily dosing regimens of tiotropium for 4 weeks, once-daily 5 MUg (evening dosing) or twice-daily 2.5 MUg (morning and evening dosing), as add-on to maintenance therapy with ICS (400-800 MUg budesonide or equivalent) as controller medication. There was no washout between treatment periods. RESULTS: An increase in the area under the curve of the 24-hour forced expiratory volume in 1 second profile from study baseline was observed following once-daily tiotropium 5 MUg (217 mL) and twice-daily 2.5 MUg (219 mL), with no difference between the two regimens (-2 mL [95% confidence interval: -38, 34]). In a subset of the study population, total tiotropium exposure, expressed as area under the plasma concentration versus time curve over 24 hours, was comparable between dosing regimens. Unexpected tiotropium plasma levels were observed in two patients, possibly because of contamination. CONCLUSIONS: The observed bronchodilator efficacy over 24 hours was similar with once-daily tiotropium 5 MUg and twice-daily 2.5 MUg as add-on to ICS therapy, supporting the suitability of once-daily dosing to provide sustained improvements in lung function in adults with symptomatic asthma. PMID- 26859539 TI - Simultaneous measurements of absorbed dose and linear energy transfer in therapeutic proton beams. AB - The biological response resulting from proton therapy depends on both the absorbed dose in the irradiated tissue and the linear energy transfer (LET) of the beam. Currently, optimization of proton therapy treatment plans is based only on absorbed dose. However, recent advances in proton therapy delivery have made it possible to vary the LET distribution for potential therapeutic gain, leading to investigations of using LET as an additional parameter in plan optimization. Having a method to measure and verify both absorbed dose and LET as part of a quality assurance program would be ideal for the safe delivery of such plans. Here we demonstrated the potential of an optically stimulated luminescence (OSL) technique to simultaneously measure absorbed dose and LET. We calibrated the ratio of ultraviolet (UV) to blue emission intensities from Al2O3:C OSL detectors as a function of LET to facilitate LET measurements. We also calibrated the intensity of the blue OSL emission for absorbed dose measurements and introduced a technique to correct for the LET-dependent dose response of OSL detectors exposed to therapeutic proton beams. We demonstrated the potential of our OSL technique by using it to measure LET and absorbed dose under new irradiation conditions, including patient-specific proton therapy treatment plans. In the beams investigated, we found the OSL technique to measure dose-weighted LET within 7.9% of Monte Carlo-simulated values and absorbed dose within 2.5% of ionization chamber measurements. PMID- 26859541 TI - Enhancing Tissue in the Internal Auditory Canal After Retrosigmoid Vestibular Schwannoma Resection. PMID- 26859540 TI - Intracochlear Drug Delivery Through the Oval Window in Fresh Cadaveric Human Temporal Bones. AB - HYPOTHESIS: Drug delivered to the oval window can diffuse to the apex of the human cochlea. BACKGROUND: We have previously demonstrated that zoledronate, a nitrogen-containing bisphosphonate, can arrest the sensorineural hearing loss in cochlear otosclerosis. We have also shown that, in animals, delivery of bisphosphonate into the cochlea can dramatically increase delivery efficiency. Intracochlear drug delivery has the potential to increase local concentration of drug while decreasing the risk of systemic toxicity. In the present study, a fluorescently labeled bisphosphonate compound (6-FAM-ZOL) was introduced into the human cochlea through the oval window and its distribution within the temporal bone was quantified. METHODS: In three fresh human temporal bones, we introduced 6-FAM-ZOL via the oval window. We compared these specimens to control specimens treated with artificial perilymph alone. Specimens were then processed, embedded into methyl methacrylate, and ground to the mid-modiolar axis. We quantified the fluorescence in confocal images. RESULTS: We found 6-FAM-ZOL to be distributed up to the apical cochlear turn. In specimens treated with 6-FAM-ZOL, we identified a strong baso-apical gradient of fluorescent signal along the lateral cochlear wall and the modiolus both in the scala vestibuli and in the scala tympani. CONCLUSION: Bisphosphonate introduced via the oval window in the human cochlea can be delivered up to the apical cochlear turn. Interscalar communication is likely to play an important role in determining patterns of drug delivery in the inner ear. PMID- 26859542 TI - Intraoperative Real-time Cochlear Response Telemetry Predicts Hearing Preservation in Cochlear Implantation. AB - AIM: To monitor cochlear function during cochlear implantation and determine correlations with postoperative acoustic hearing. BACKGROUND: Cochlear response telemetry measures cochlear function directly from cochlear implant electrodes. We have adapted this system to provide real-time cochlear response telemetry (RT CRT) monitoring of a patient's acoustic hearing as the cochlear implant electrode array is inserted. METHODS: Eighteen subjects (1 child and 17 adults) with sloping high frequency hearing loss were implanted with Cochlear Ltd slim straight arrays (CI422/CI522). Tone bursts (500 Hz, 100-110 dB) were presented at 14 Hz continuously during the array insertion. RT-CRT amplitudes were correlated with surgical manoeuvres recorded on the video from the operating microscope and with postoperative pure tone audiograms. RESULTS: Despite an excellent overall rate of complete or partial hearing preservation (79%), RT-CRT identified that in 47% of these implantations there was transient or permanent reduction in the amplitude of the cochlear microphonic (CM). Patients with a preserved CM at the end of insertion had on average 15 dB better low-frequency hearing preservation. The CM amplitude was most vulnerable during the last few millimeters of insertion or when inadvertent movement of the array occurred after full insertion. Physical contact/elevation of the basilar membrane is hypothesized as a likely mechanism of hearing loss rather than overt physical trauma. CONCLUSION: RT-CRT can be used to predict early postoperative hearing loss and to potentially refine surgical technique. In the future, feedback of RT-CRT may prove to be a valuable tool for maximizing preservation of residual hearing or providing feedback on electrode contact with the basilar membrane. PMID- 26859543 TI - Intratympanic Iodine Contrast Injection Diffuses Across the Round Window Membrane Allowing for Perilymphatic CT Volume Acquisition Imaging. AB - HYPOTHESIS: Whether the round window membrane (RWM) is permeable to iodine-based contrast agents (IBCA) is unknown; therefore, our goal was to determine if IBCAs could diffuse through the RWM using CT volume acquisition imaging. INTRODUCTION: Imaging of hydrops in the living human ear has attracted recent interest. Intratympanic (IT) injection has shown gadolinium's ability to diffuse through the RWM, enhancing the perilymphatic space. METHODS: Four unfixed human cadaver temporal bones underwent intratympanic IBCA injection using three sequentially studied methods. The first method was direct IT injection. The second method used direct RWM visualization via tympanomeatal flap for IBCA-soaked absorbable gelatin pledget placement. In the third method, the middle ear was filled with contrast after flap elevation. Volume acquisition CT images were obtained immediately postexposure, and at 1-, 6-, and 24-hour intervals. Postprocessing was accomplished using color ramping and subtraction imaging. RESULTS: After the third method, positive RWM and perilymphatic enhancement were observed with endolymph sparing. Gray scale and color ramp multiplanar reconstructions displayed increased signal within the cochlea compared with precontrast imaging. The cochlea was measured for attenuation differences compared with pure water, revealing a preinjection average of -1,103 HU and a postinjection average of 338 HU. Subtraction imaging shows enhancement remaining within the cochlear space, Eustachian tube, middle ear epithelial lining, and mastoid. CONCLUSION: Iohexol iodine contrast is able to diffuse across the RWM. Volume acquisition CT imaging was able to detect perilymphatic enhancement at 0.5-mm slice thickness. The clinical application of IBCA IT injection seems promising but requires further safety studies. PMID- 26859544 TI - Endoscopically Guided Transtympanic Balloon Catheter Dilatation of the Eustachian Tube: A Cadaveric Pilot Study. AB - OBJECTIVE: To assess the feasibility, safety, and efficacy of transtympanic balloon catheter dilatation of the Eustachian tube (ET) in a cadaver model. PATIENTS AND INTERVENTIONS: A cadaveric study of 10 cadaver heads, which underwent unilateral transtympanic dilatation of the ET with a 3 * 20 mm balloon catheter with full endoscopic guidance and visualization. RESULTS: Procedural safety was demonstrated, with no damage to any essential structures found. Feasibility of the procedure was demonstrated in all cadavers with 100% success rate, despite a small number of encountered difficulties. Statistically significant efficacy was also demonstrated in both radiologic and manometric data. CONCLUSION: With full endoscopic visualization, the transtympanic approach to balloon catheter dilatation of the ET seems to be a feasible and safe procedure in the cadaver model. PMID- 26859545 TI - Fifty Years of the American Neurotology Society. AB - Last year (2015) marked the 50th Anniversary of the American Neurotology Society (ANS). The past 50 years has observed significant progress in the fields of otology and neurotology. Progress did not come without controversies and conflicts. Nonetheless, the ANS flourished throughout this time. To isolate the workings of the ANS from the broader fields of otology and neurotology would be impossible-members of the ANS were and continue to be the leaders in the field, and the topics presented at the ANS meetings reflect its leading edge. Instead, this retrospective aims to highlight significant events in the field from the vantage point of the ANS, using the biannual ANS meeting programs are the primary source material. PMID- 26859546 TI - Prevalence of Pulsatile Tinnitus Among Patients With Migraine. AB - OBJECTIVE: To examine the prevalence of pulsatile tinnitus (PT) among patients with a diagnosis of migraine and to determine if treatment of migraine improves symptoms. STUDY DESIGN: Single-institution retrospective patient review. SETTING: Academic tertiary referral center. PATIENTS: Billing data capturing ICD-9 codes 346.xx and 388.3x was used to identify patients with history of migraine and tinnitus. Patients were excluded if the symptom of PT could be attributed to an alternate diagnosis. Data were extracted from the patients' electronic medical records. INTERVENTION(S): Therapeutic patients were prescribed a strict migraine diet with or without migraine medication. MAIN OUTCOME MEASURE(S): Subjective improvement in tinnitus as documented in electronic medical records. RESULTS: One thousand two hundred four patients were identified with an ICD-9 code for migraine and of those patients, 12% (n = 145) had an ICD-9 code for tinnitus. After ruling out alternative causes, the prevalence of PT among all patients with migraine was 1.9%. Of migrainers with PT who underwent migraine treatment, 11 out of 16 reported resolution or improvement of their PT. CONCLUSION: PT can be observed in the context of migraine. Migraine treatment with avoidance of dietary triggers with or without medication can possibly lead to resolution of PT. PMID- 26859547 TI - Effects of an Intraoperative Dexmedetomidine Bolus on the Postoperative Blood Pressure and Pain Subsequent to Craniotomy for Supratentorial Tumors. AB - BACKGROUND: Control of emergence hypertension and pain is important after craniotomy for monitoring the neurological status. This prospective double blinded study investigated the hemodynamics after a single bolus of dexmedetomidine (DEX) infusion administered to the patient undergoing craniotomy under general anesthesia, and its effect on emergence hypertension and postsurgical pain. METHODS: Adult patients scheduled for elective surgery for supratentorial tumors were randomized to receive a 10-minute intraoperative DEX infusion of 0.4 MUg/kg (small dose, n=43) or 0.8 MUg/kg (medium dose, n=46), or normal saline (vehicle control, n=45), ~60 minutes before the end of anesthesia. RESULTS: A transient increase in the blood pressure associated with DEX was observed; 53.5% and 91.3% of the patients in the small-dose and the medium-dose groups, respectively, required treatment. Emergence mean arterial pressure and heart rates were significantly lower in the DEX groups compared with the control group. Incidence rates of postoperative hypertension in the small-dose (16.3%) and the medium-dose groups (15.2%) were significantly lower relative to that of the control group (35.6%). Patients who received DEX had a lower Verbal Numerical Rating Scale (VNRS) score in the neurosurgical ICU than the control group, and postsurgical pain (VNRS>=4) was lower in the medium-dose group (41.3%) than in the control group (71.1%). No shivering was observed in the medium-dose group, which was significantly less than that of the other 2 groups. CONCLUSIONS: An intraoperative bolus of DEX risks a transient increase in mean arterial pressure, but controls emergence hypertension effectively. Dose-related reductions in postsurgical pain and shivering were observed. PMID- 26859548 TI - Pierre Robin Sequence With Full Stomach for Emergency Ventriculoperitoneal Shunt: Anesthetic Challenges. PMID- 26859551 TI - Corrigendum: Drosophila Rif1 is an essential gene and controls late developmental events by direct interaction with PP1-87B. PMID- 26859552 TI - Metabolic effects of bile acid sequestration: impact on cardiovascular risk factors. AB - PURPOSE OF REVIEW: This article discusses the impact of bile acid sequestrants (BAS) on cardiovascular risk factors (CVRFs), on the basis of recent (pre)clinical studies assessing the metabolic impact of modulation of enterohepatic bile acid signaling via the bile acid receptors farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5). RECENT FINDINGS: BAS decrease low-density lipoprotein-cholesterol by stimulating de novo hepatic bile acid synthesis and lowering intestinal lipid absorption, and improve glucose homeostasis in type 2 diabetes mellitus, at least in part by increasing GLP-1 production, via intestinal TGR5- and FXR-dependent mechanisms. Intestinal and peripheral FXR and TGR5 modulation also affects peripheral tissues, which can contribute to the reduction of CVRFs. SUMMARY: Bile acids are regulators of metabolism acting in an integrated interorgan manner via FXR and TGR5. Modulation of the bile acid pool size and composition, and selective interference with their receptors could, therefore, be a therapeutic approach to decrease CVRFs. Even though clinical cardiovascular outcome studies using BAS are still lacking, the existing data point to BAS as an efficacious pharmacological approach to reduce CVRFs. PMID- 26859550 TI - Delivery, Effect on Cell Viability, and Plasticity of Modified Aptamer Constructs. AB - AS1411 is a g-quadruplex-forming aptamer capable of selectively entering cancer cells by nucleolin receptor-mediated uptake. In this study, we investigated the cell internalization properties and plasticity of AS1411 carrying different locked nucleic acid-containing cargo oligonucleotides (ONs) for delivery into A549 and U2OS cells. We found that internalization efficiency is highly governed by ON cargo chemistry and composition since the inherent antitumor properties of AS1411 were lost when attached to a nontoxic ON, noTox. However, a toxic ON, Tox, demonstrated potent cytotoxicity after aptamer-mediated uptake in A549 cells. We also examined the effect of unlocked nucleic acid (UNA) modifications in the loop region of the aptamer, and how the cargo ONs and UNA incorporation affect the secondary structure of AS1411, in the presence or absence of two novel ellipticine derivatives. These findings add new insights to the design and future applications of aptamer-guided delivery of ON cargo to cancer cells. PMID- 26859553 TI - What role will proprotein convertase subtilisin/kexin type 9 inhibitors play in hyperlipidemia management? AB - PURPOSE OF REVIEW: This article summarizes the role that the recently approved proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) will play in LDL cholesterol management. RECENT FINDINGS: The discovery of PCSK9 in 2003 and its association with a rare form of autosomal-dominant hypercholesterolemia quickly led to the understanding of the role of circulating PCSK9 in regulating the recycling of the LDL receptor and LDL cholesterol (LDL-C) and impact on cardiovascular disease. Development of monoclonal antibodies that bind and inhibit PCSK9 entered clinical development in late 2009 and demonstrated substantial LDL-C reductions as monotherapy, added to statins, in heterozygous familial hypercholesterolemia and patients intolerant of statins. Large and comprehensive trials over the last 5 years also indicated good tolerability and safety and resulted in the 2015 regulatory approval in the USA and Europe for the marketing of two mAbs, evolocumab and alirocumab, for the treatment of LDL-C. SUMMARY: The background, clinical trials and approved indications for the current PCSK9 inhibitors are reviewed along with their likely role in the management of LDL-C and cardiovascular disease prevention. PMID- 26859554 TI - Misidentification Delusions: Prevalence in Different Types of Dementia and Validation of a Structured Questionnaire. AB - Misidentification delusions (MDs) are considered relatively rare psychopathologic phenomena that may occur within the context of psychiatric or neurological conditions. The purpose of this study was to assess the prevalence of MD in different types of dementia, correlate the presence of MD with demographic and clinical variables, and validate a specific questionnaire. We examined 146 subjects with Alzheimer disease, 21 with Lewy body dementia, 6 with frontotemporal dementia, and 13 with vascular dementia (subcortical type), who were consecutively enrolled in the study from 2 Memory Clinics. Patients had a mean age of 78.7+/-6.4 years and an Mini-Mental State Examination average score of 16.9+/-6.1. The Neuropsychiatric Inventory delusion subscale and a new Misidentification Delusion Questionnaire aimed at specific assessment of 11 delusional misidentification syndromes were administrated to the caregivers. On the basis of the Neuropsychiatric Inventory, MDs were present in 33.3% of the subjects, whereas according to the Misidentification Delusion Questionnaire they were present in 36.0% of the subjects. Specifically, 34.2% of Alzheimer disease, 52.4% of Lewy body dementia, and 46.1% of vascular dementia patients experienced at least 1 MD. None of the patients with frontotemporal dementia developed MD. The most frequent MD was house misidentification, followed by splitting of people and reduplicative paramnesia. Our self-administered questionnaire proved to be an accurate and specific tool for the detection of MD. PMID- 26859555 TI - New concept of traction force applied to biliary self-expandable metallic stents. AB - BACKGROUND AND STUDY AIMS: Various mechanical properties of self-expandable metallic stents (SEMSs) have been reported. They can be classified into the device behavior during and after deployment. While there have been several reports on the latter, information on the former is insufficient. During deployment, the position is maintained by retracting the delivery catheter. We propose that this pulling force be called the traction force and that the magnitude of traction force is termed the traction momentum. The aim of this study was to measure these parameters in order to clarify the properties of SEMSs in terms of their deployment. MATERIAL AND METHODS: The traction force, traction momentum, and shortening rate of 10 different SEMSs were measured. Traction force was measured using in-house equipment, and the shortening rate was determined by measuring the stents. RESULTS: The shortening rate was closely related to the stent structure. The traction force varied between 1.5 N and 9.4 N, and the traction momentum was significantly elevated in covered and braided stents. A high traction force did not imply a high traction momentum. CONCLUSIONS: A low or constant traction force and a minimal shortening rate significantly facilitated SEMS deployment to optimal positions. Traction force could be an important element for new ideal SEMS design. PMID- 26859556 TI - Endoscopic management with multiple plastic stents of anastomotic biliary stricture following liver transplantation: long-term results. AB - BACKGROUND AND AIMS: Anastomotic biliary stricture (ABS) is the most common biliary complication after orthotopic liver transplantation (OLT) and can be successfully managed endoscopically. The long-term results of a protocol using placement of multiple plastic stents to treat ABS following OLT were analyzed. METHODS: All patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for OLT-related biliary complications at our Endoscopy Unit between July 1994 and March 2012 were retrospectively identified from the ERCP database. Patients with an ABS treated with an increasing number of plastic stents were included in the study. Follow-up after stent removal was obtained by telephone contact with the patient and/or referring physician and by liver function tests (LFTs) evaluation. RESULTS: 56 patients, treated with an increasing number of plastic stents until resolution of the stricture, were included. Five patients were then excluded (unrelated death during treatment, n = 3; incomplete treatment because of poor compliance, n = 2), and 51/56 patients reached study end points and were included in the analysis. Resolution of ABS was obtained in 50/51 patients; 1 patient required hepaticojejunostomy because of failure to pass the stricture with the guidewire (per protocol resolution, 98 %). Mean duration of endoscopic treatment was 11.5 months, with a median 4 ERCPs per patient. Immediate ERCP-related adverse events occurred in 3/56 patients (5.4 %). After a median follow-up of 5.8 years from stent removal, 3/50 patients (6 %) had recurrence of ABS. These 3 patients were successfully treated again endoscopically and are asymptomatic after a further median follow-up of 5.6 years. CONCLUSIONS: At long-term follow-up, endoscopic treatment with multiple plastic stents of ABS following OLT appeared to be effective in most patients. Stricture recurrence is rare and can be successfully treated again endoscopically. PMID- 26859557 TI - New technologies in benign prostatic hyperplasia management. AB - PURPOSE OF REVIEW: Surgical debulking of the adenoma/transition zone has been the fundamental principle which underpins transurethral resection of the prostate - still acknowledged to be the gold-standard therapy for benign prostatic hyperplasia (BPH). However, there has been a recent resurgence in development of new BPH technologies driven by enhanced understanding of prostate pathophysiology, development of new ablative technologies, and the need for less morbid alternatives as the mean age and complexity of the treatment population continues to increase. The objective of this review is to highlight new BPH technologies and review their available clinical data with specific emphasis on unique features of the technology, procedural effectiveness and safety, and potential impact on current treatment paradigms. RECENT FINDINGS: New technologies have emerged that alter the shape of the prostate to decrease urinary obstruction and enhance delivery of a lethal thermal dose by steam injection into the transition zone of the prostate. Energy can be delivered to the prostate via a beam of high-pressure saline or focused acoustic energy to mechanically disintegrate prostate tissue. Methods of cell death are being targeted with selectivity by the arterial supply with embolization and specific to prostate cells via injectable biological therapies. SUMMARY: A number of new technologies are at various stages of development and improve on the transurethral resection of the prostate paradigm by moving closer to the ideal BPH therapy which is definitive, can be performed in minutes, in the office setting, with only local anesthesia and oral sedation. PMID- 26859559 TI - Effect of Short-Term Supplementation with Ready-to-Use Therapeutic Food or Micronutrients for Children after Illness for Prevention of Malnutrition: A Randomised Controlled Trial in Nigeria. AB - BACKGROUND: Globally, Medecins Sans Frontieres (MSF) treats more than 300,000 severely malnourished children annually. Malnutrition is not only caused by lack of food and poor infant and child feeding practices but also by illnesses. Breaking the vicious cycle of illness and malnutrition by providing ill children with nutritional supplementation is a potentially powerful strategy for preventing malnutrition that has not been adequately investigated. Therefore, MSF investigated whether incidence of malnutrition among ill children <5 y old could be reduced by providing a fortified food product or micronutrients during their 2 wk convalescence period. Two trials, one in Nigeria and one in Uganda, were conducted; here we report on the trial that took place in Goronyo, a rural region of northwest Nigeria with high morbidity and malnutrition rates. METHODS AND FINDINGS: We investigated the effect of supplementation with ready-to-use therapeutic food (RUTF) and a micronutrient powder (MNP) on the incidence of malnutrition in ill children presenting at an outpatient clinic in Goronyo during February to September 2012. A three-armed, partially-blinded, randomised controlled trial was conducted in children diagnosed as having malaria, diarrhoea, or lower respiratory tract infection. Children aged 6 to 59 mo were randomised to one of three arms: one sachet/d of RUTF; two sachets/d of micronutrients or no supplement (control) for 14 d for each illness over 6 mo. The primary outcome was the incidence of first negative nutritional outcome (NNO) during the 6 mo follow-up. NNO was a study-specific measure used to indicate occurrence of malnutrition; it was defined as low weight-for-height z-score (<-2 for non-malnourished and <-3 for moderately malnourished children), mid-upper arm circumference <115 mm, or oedema, whichever came first. Of the 2,213 randomised participants, 50.0% were female and the mean age was 20.2 (standard deviation 11.2) months; 160 (7.2%) were lost to follow-up, 54 (2.4%) were admitted to hospital, and 29 (1.3%) died. The incidence rates of NNO for the RUTF, MNP, and control groups were 0.522 (95% confidence interval (95% CI), 0.442-0.617), 0.495 (0.415-0.589), and 0.566 (0.479-0.668) first events/y, respectively. The incidence rate ratio was 0.92 (95% CI, 0.74-1.15; p = 0.471) for RUTF versus control; 0.87 (0.70-1.10; p = 0.242) for MNP versus control and 1.06 (0.84-1.33, p = 0.642) for RUTF versus MNP. A subgroup analysis showed no interaction nor confounding, nor a different effectiveness of supplementation, among children who were moderately malnourished compared with non-malnourished at enrollment. The average number of study illnesses for the RUTF, MNP, and control groups were 4.2 (95% CI, 4.0-4.3), 3.4 (3.2-3.6), and 3.6 (3.4-3.7). The proportion of children who died in the RUTF, MNP, and control groups were 0.8% (95% CI, 0.3-1.8), 1.8% (1.0-3.3), and 1.4% (0.7-2.8). CONCLUSIONS: A 2-wk supplementation with RUTF or MNP to ill children as part of routine primary medical care did not reduce the incidence of malnutrition. The lack of effect in Goronyo may be due to a high frequency of morbidity, which probably further affects a child's nutritional status and children's ability to escape from the illness-malnutrition cycle. The duration of the supplementation may have been too short or the doses of the supplements may have been too low to mitigate the effects of high morbidity and pre-existing malnutrition. An integrated approach combining prevention and treatment of diseases and treatment of moderate malnutrition, rather than prevention of malnutrition by nutritional supplementation alone, might be more effective in reducing the incidence of acute malnutrition in ill children. TRIAL REGISTRATION: clinicaltrials.gov NCT01154803. PMID- 26859560 TI - Occupational Injuries in Germany: Population-Wide National Survey Data Emphasize the Importance of Work-Related Factors. AB - Unintentional injuries cause much of the global mortality burden, with the workplace being a common accident setting. Even in high-income economies, occupational injury figures remain remarkably high. Because risk factors for occupational injuries are prone to confounding, the present research takes a comprehensive approach. To better understand the occurrence of occupational injuries, sociodemographic factors and work- and health-related factors are tested simultaneously. Thus, the present analysis aims to develop a comprehensive epidemiological model that facilitates the explanation of varying injury rates in the workplace. The representative phone survey German Health Update 2010 provides information on medically treated occupational injuries sustained in the year prior to the interview. Data were collected on sociodemographics, occupation, working conditions, health-related behaviors, and chronic diseases. For the economically active population (18-70 years, n = 14,041), the 12-month prevalence of occupational injuries was calculated with a 95% confidence interval (CI). Blockwise multiple logistic regression was applied to successively include different groups of variables. Overall, 2.8% (95% CI 2.4-3.2) of the gainfully employed population report at least one occupational injury (women: 0.9%; 95% CI 0.7-1.2; men: 4.3%; 95% CI 3.7-5.0). In the fully adjusted model, male gender (OR 3.16) and age 18-29 (OR 1.54), as well as agricultural (OR 5.40), technical (OR 3.41), skilled service (OR 4.24) or manual (OR 5.12), and unskilled service (OR 3.13) or manual (OR 4.97) occupations are associated with higher chances of occupational injuries. The same holds for frequent stressors such as heavy carrying (OR 1.78), working in awkward postures (OR 1.46), environmental stress (OR 1.48), and working under pressure (OR 1.41). Among health-related variables, physical inactivity (OR 1.47) and obesity (OR 1.73) present a significantly higher chance of occupational injuries. While the odds for most work-related factors were as expected, the associations for health-related factors such as smoking, drinking, and chronic diseases were rather weak. In part, this may be due to context-specific factors such as safety and workplace regulations in high income countries like Germany. This assumption could guide further research, taking a multi-level approach to international comparisons. PMID- 26859561 TI - A Murine, Bispecific Monoclonal Antibody Simultaneously Recognizing beta-Glucan and MP65 Determinants in Candida Species. AB - There is a real medical need of new diagnostic tools for the early recognition of invasive Candida infections. We exploited a rather simple and rapid redox methodology to construct a bispecific monoclonal antibody (bsmAb) that combines a monoclonal antibody (mAb) directed against 1,3-beta-D-glucan, a well-known, pan fungal diagnostic biomarker, with a mAb recognizing MP65, a major immunogenic mannoprotein secreted by C.albicans and other Candida species. The bsmAb (MP65/bglu mAb) was successfully produced and purified at high yields and proved to bind and reveal simultaneously, with high sensitivity, the beta-glucan and MP65 antigens in both purified and native forms. The MP65/bglu mAb is the first bispecific antibody generated against a fungal microorganism and may prove useful for the concurrent detection of different and clinically significant Candida biomarkers in patient sera. PMID- 26859562 TI - It Depends Who Is Watching You: 3-D Agent Cues Increase Fairness. AB - Laboratory and field studies have demonstrated that exposure to cues of intentional agents in the form of eyes can increase prosocial behavior. However, previous research mostly used 2-dimensional depictions as experimental stimuli. Thus far no study has examined the influence of the spatial properties of agency cues on this prosocial effect. To investigate the role of dimensionality of agency cues on fairness, 345 participants engaged in a decision-making task in a naturalistic setting. The experimental treatment included a 3-dimensional pseudo realistic model of a human head and a 2-dimensional picture of the same object. The control stimuli consisted of a real plant and its 2-D image. Our results partly support the findings of previous studies that cues of intentional agents increase prosocial behavior. However, this effect was only found for the 3-D cues, suggesting that dimensionality is a critical variable in triggering these effects in a real-world settings. Our research sheds light on a hitherto unexplored aspect of the effects of environmental cues and their morphological properties on decision-making. PMID- 26859564 TI - The Mediating Relation between Symbolic and Nonsymbolic Foundations of Math Competence. AB - This study investigated the relation between symbolic and nonsymbolic magnitude processing abilities with 2 standardized measures of math competence (WRAT Arithmetic and KeyMath Numeration) in 150 3rd-grade children (mean age 9.01 years). Participants compared sets of dots and pairs of Arabic digits with numerosities 1-9 for relative numerical magnitude. In line with previous studies, performance on both symbolic and nonsymbolic magnitude processing was related to math ability. Performance metrics combining reaction and accuracy, as well as weber fractions, were entered into mediation models with standardized math test scores. Results showed that symbolic magnitude processing ability fully mediates the relation between nonsymbolic magnitude processing and math ability, regardless of the performance metric or standardized test. PMID- 26859563 TI - Spatial Genetic Structure of the Abundant and Widespread Peatmoss Sphagnum magellanicum Brid. AB - Spore-producing organisms have small dispersal units enabling them to become widespread across continents. However, barriers to gene flow and cryptic speciation may exist. The common, haploid peatmoss Sphagnum magellanicum occurs in both the Northern and Southern hemisphere, and is commonly used as a model in studies of peatland ecology and peatmoss physiology. Even though it will likely act as a rich source in functional genomics studies in years to come, surprisingly little is known about levels of genetic variability and structuring in this species. Here, we assess for the first time how genetic variation in S. magellanicum is spatially structured across its full distribution range (Northern Hemisphere and South America). The morphologically similar species S. alaskense was included for comparison. In total, 195 plants were genotyped at 15 microsatellite loci. Sequences from two plastid loci (trnG and trnL) were obtained from 30 samples. Our results show that S. alaskense and almost all plants of S. magellanicum in the northern Pacific area are diploids and share the same gene pool. Haploid plants occur in South America, Europe, eastern North America, western North America, and southern Asia, and five genetically differentiated groups with different distribution ranges were found. Our results indicate that S. magellanicum consists of several distinct genetic groups, seemingly with little or no gene flow among them. Noteworthy, the geographical separation of diploids and haploids is strikingly similar to patterns found within other haploid Sphagnum species spanning the Northern Hemisphere. Our results confirm a genetic division between the Beringian and the Atlantic that seems to be a general pattern in Sphagnum taxa. The pattern of strong genetic population structuring throughout the distribution range of morphologically similar plants need to be considered in future functional genomic studies of S. magellanicum. PMID- 26859565 TI - Epstein-Barr Virus Infection in Gastric Remnant Carcinoma and Recurrent Gastric Carcinoma in Qingdao of Northern China. AB - BACKGROUND: Epstein-Barr virus (EBV) is associated with a subset of gastric carcinoma which was defined as EBV associated gastric carcinoma (EBVaGC). The proportion of EBVaGC in gastric remnant carcinoma (GRC) which occurs in the intact stomach five or more years after gastric surgery for benign disease is significantly higher than that in conventional gastric carcinoma (CGC). The infection of EBV in recurrent gastric carcinoma (RGC) with local anastomotic recurrence is poorly understood. METHODS: 53 cases of GRC and 58 cases of RGC were analyzed for the presence of EBV, and the variants of EBV Encoded RNAs (EBER), EBV Nuclear Antigen 1 (EBNA1) and Latent Membrane Protein 1 (LMP1) gene in both groups were investigated. RESULTS: Thirteen (24.5%) out of 53 GRC cases and 3 (5.2%) out of 58 RGC cases were identified as EBVaGCs. In 17 paired RGC cases, only one case was classified as EBVaGC in both times specimen. Another one case was identified as EBVaGC in the primary gastroectomy specimen while the recurrent gastric cancer was not. The third EBVaGC in RGC was identified while the primary gastric cancer was not EBVaGC. In GRC and RGC cases, type 1, type F, EB-6m, V-val subtype, del-LMP1 were predominant type or variants, accounting for 10(76.9%) and 2(66.7%), 13(100%) and 3(100%), 13(100%) and 3(100%), 9(69.2%) and 3(100%), 12(92.3%) and 3(100%), respectively. However, Type C was the predominant type in GRC accounting for 9(69.2%) cases while type D was the predominant one accounting for 2(66.7%) cases in RGC. CONCLUSIONS: The prevalence of EBVaGc in GRC and RGC was significantly different. The distributions of these variants were similar to each other in the two groups which indicated that there were no more aggressive EBV variants in EBVaGC in GRC compared with that in RGC. PMID- 26859567 TI - Physiological Reduction in Left Ventricular Contractile Function in Healthy Postpartum Women: Potential Overlap with Peripartum Cardiomyopathy. AB - AIMS: Peripartum cardiomyopathy is a potentially life-threatening cause of heart failure, commoner in Afro-Caribbean than Caucasian women. Its diagnosis can be challenging due to physiological changes in cardiac function that also occur in healthy women during the early postpartum period. This study aimed to (i) establish the overlap between normal cardiac physiology in the immediate postpartum period and pathological changes in peripartum cardiomyopathy ii) identify any ethnicity-specific changes in cardiac function and cardiac biomarkers in healthy postpartum women. METHODS AND RESULTS: We conducted a cross sectional study of 58 healthy postpartum women within 48 hours of delivery and 18 matched non-pregnant controls. Participants underwent cardiac assessment by echocardiography and strain analysis, including 3D echocardiography in 40 postpartum women. Results were compared with 12 retrospectively studied peripartum cardiomyopathy patients. Healthy postpartum women had significantly higher left ventricular volumes and mass, and lower ejection fraction and global longitudinal strain than non-pregnant controls. These parameters were significantly more impaired in peripartum cardiomyopathy patients but with overlapping ranges of values. Healthy postpartum women had higher levels of adrenomedullin, placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt1) compared to controls. The postpartum state, adrenomedullin, sFlt1 and the sFlt1:PlGF ratio were independent predictors of LV remodelling and function in healthy postpartum women. CONCLUSION: Healthy postpartum women demonstrate several echocardiographic indicators of left ventricular remodelling and reduced function, which are associated with altered levels of angiogenic and cardiac biomarkers. PMID- 26859566 TI - Impact of Estrogen Therapy on Lymphocyte Homeostasis and the Response to Seasonal Influenza Vaccine in Post-Menopausal Women. AB - It is widely recognized that changes in levels of ovarian steroids modulate severity of autoimmune disease and immune function in young adult women. These observations suggest that the loss of ovarian steroids associated with menopause could affect the age-related decline in immune function, known as immune senescence. Therefore, in this study, we determined the impact of menopause and estrogen therapy (ET) on lymphocyte subset frequency as well as the immune response to seasonal influenza vaccine in three different groups: 1) young adult women (regular menstrual cycles, not on hormonal contraception); 2) post menopausal (at least 2 years) women who are not receiving any form of hormone therapy (HT) and 3) post-menopausal hysterectomized women receiving ET. Although the numbers of circulating CD4 and CD20 B cells were reduced in the post menopausal group receiving ET, we also detected a better preservation of naive B cells, decreased CD4 T cell inflammatory cytokine production, and slightly lower circulating levels of the pro-inflammatory cytokine IL-6. Following vaccination, young adult women generated more robust antibody and T cell responses than both post-menopausal groups. Despite similar vaccine responses between the two post menopausal groups, we observed a direct correlation between plasma 17beta estradiol (E2) levels and fold increase in IgG titers within the ET group. These findings suggest that ET affects immune homeostasis and that higher plasma E2 levels may enhance humoral responses in post-menopausal women. PMID- 26859568 TI - Trends in Food Habits and Their Relation to Socioeconomic Status among Nordic Adolescents 2001/2002-2009/2010. AB - BACKGROUND: In the Nordic countries, substantial policy and intervention efforts have been made to increase adolescents' consumption of fruit and vegetables and to reduce their intake of sweets and soft drinks. Some initiatives have been formulated in a Nordic collaboration and implemented at national level. In recent years, social inequalities in food habits have been attracted particular governmental interest and several initiatives addressing the socioeconomic gradient in food habits have been highlighted. However, few internationally published studies have evaluated how trends in adolescents' food habits develop in the context of Nordic nutrition policy, or have compared differences between the Nordic countries. METHODS: The study was based on Danish, Finnish, Norwegian and Swedish cross-sectional data from the international Health Behaviour in School-Aged Children (HBSC) study, collected via three nationally representative and comparable questionnaire surveys in 2001/2002, 2005/2006 and 2009/2010. Food habits were identified by students' consumption of fruit, vegetables, sweets and sugar sweetened soft drink. Socioeconomic status (SES) was measured with the Family Affluence Scale (FAS). Multilevel logistic regression was used to analyze the data. RESULTS: Trends in fruit consumption developed differently across countries, characterized by an increase in Denmark and Norway and more stable trends in Sweden and Finland. Vegetable consumption increased particularly in Denmark and to a lesser extent in Norway, whereas Sweden and Finland displayed stable trends. Decreased trends were observed for sweet and soft drink consumption and were similar in Norway, Sweden and Finland. Sweet consumption decreased across all survey years, whereas soft drink consumption decreased between 2001/2002-2005/2006 and was stable thereafter. Denmark displayed an increase between 2001/2002-2005/2006 followed by a similar decrease between 2005/2006-2009/2010 for both sweet and soft drink consumption. Socioeconomic inequalities in fruit and vegetable consumption were observed in all countries, with no cross-country differences, and no changes over time. Small but not significant cross-country variation was identified for SES inequalities in sweet consumption. Reduced SES inequalities were observed in Sweden between 2005/2006 and 2009/2010. SES was not associated with soft drink consumption in this study population, with the exception of Denmark for the survey year 2009/2010. CONCLUSION: Different trends resulted in increased country differences in food habits during the time of observations. In survey year 2009/2010, Danish students reported a higher intake of fruit and vegetable consumption than their counterparts in the other Nordic countries. Finnish students reported the lowest frequency of sweets and soft drink consumption. Despite the positive dietary trends documented in the present study, the majority of Nordic adolescents are far from meeting national dietary recommendations. Our findings underline the need for more comprehensive initiatives targeting young people's food habits as well as a more deliberate and focused action to close gaps in social inequalities that affect food choices. PMID- 26859569 TI - Metal Concentrations in the Liver and Stable Isotope Ratios of Carbon and Nitrogen in the Muscle of Silvertip Shark (Carcharhinus albimarginatus) Culled off Ishigaki Island, Japan: Changes with Growth. AB - We analyzed Hg, Cd, Zn, Cu and Fe concentrations in liver samples as well as the Hg concentration and stable isotope ratios of carbon and nitrogen (delta13C and delta15N) in muscle samples from silvertip sharks (Carcharhinus albimarginatus) in Japan. Muscular and hepatic Hg concentrations increased with increased body length. However, these increases were more prominent in the liver than in the muscle samples, and appeared to occur after maturation. Hepatic Zn and Cu concentrations decreased during the growth stage, and then increased concomitantly thereafter with increases in Cd burden. Hepatic Fe concentration from males increased proportionally with increases in body length, whereas no increase was observed in samples from females, probably due to the mother-to embryo transfer of Fe. The delta13C values tended to decrease with increases in body length, whereas no decrease in the delta15N values was observed. PMID- 26859570 TI - Converging Evidence of Ubiquitous Male Bias in Human Sex Perception. AB - Visually judging the sex of another can be achieved easily in most social encounters. When the signals that inform such judgements are weak (e.g. outdoors at night), observers tend to expect the presence of males-an expectation that may facilitate survival-critical decisions under uncertainty. The present aim was to examine whether this male bias depends on expertise. To that end, Caucasian and Asian observers targeted female and male hand images that were either the same or different to the observers' race (i.e. long term experience was varied) while concurrently, the proportion of targets changed across presentation blocks (i.e. short term experience change). It was thus found that: (i) observers of own-race stimuli were more likely to report the presence of males and absence of females, however (ii) observers of other-race stimuli--while still tending to accept stimuli as male--were not prone to rejecting female cues. Finally, (iii) male biased measures did not track the relative frequency of targets or lures, disputing the notion that male bias derives from prior expectation about the number of male exemplars in a set. Findings are discussed in concert with the pan stimulus model of human sex perception. PMID- 26859571 TI - Invasive mouse gastric adenocarcinomas arising from Lgr5+ stem cells are dependent on crosstalk between the Hedgehog/GLI2 and mTOR pathways. AB - Gastric adenocarcinoma is the third most common cause of cancer-related death worldwide. Here we report a novel, highly-penetrant mouse model of invasive gastric cancer arising from deregulated Hedgehog/Gli2 signaling targeted to Lgr5 expressing stem cells in adult stomach. Tumor development progressed rapidly: three weeks after inducing the Hh pathway oncogene GLI2A, 65% of mice harbored in situ gastric cancer, and an additional 23% of mice had locally invasive tumors. Advanced mouse gastric tumors had multiple features in common with human gastric adenocarcinomas, including characteristic histological changes, expression of RNA and protein markers, and the presence of major inflammatory and stromal cell populations. A subset of tumor cells underwent epithelial-mesenchymal transition, likely mediated by focal activation of canonical Wnt signaling and Snail1 induction. Strikingly, mTOR pathway activation, based on pS6 expression, was robustly activated in mouse gastric adenocarcinomas from the earliest stages of tumor development, and treatment with rapamycin impaired tumor growth. GLI2A expressing epithelial cells were detected transiently in intestine, which also contains Lgr5+ stem cells, but they did not give rise to epithelial tumors in this organ. These findings establish that deregulated activation of Hedgehog/Gli2 signaling in Lgr5-expressing stem cells is sufficient to drive gastric adenocarcinoma development in mice, identify a critical requirement for mTOR signaling in the pathogenesis of these tumors, and underscore the importance of tissue context in defining stem cell responsiveness to oncogenic stimuli. PMID- 26859572 TI - Crosstalk between Ca2+ signaling and mitochondrial H2O2 is required for rotenone inhibition of mTOR signaling pathway leading to neuronal apoptosis. AB - Rotenone, a neurotoxic pesticide, induces loss of dopaminergic neurons related to Parkinson's disease. Previous studies have shown that rotenone induces neuronal apoptosis partly by triggering hydrogen peroxide (H2O2)-dependent suppression of mTOR pathway. However, the underlying mechanism is not fully understood. Here, we show that rotenone elevates intracellular free calcium ion ([Ca2+]i) level, and activates CaMKII, resulting in inhibition of mTOR signaling and induction of neuronal apoptosis. Chelating [Ca2+]i with BAPTA/AM, preventing extracellular Ca2+ influx using EGTA, inhibiting CaMKII with KN93, or silencing CaMKII significantly attenuated rotenone-induced H2O2 production, mTOR inhibition, and cell death. Interestingly, using TTFA, antimycin A, catalase or Mito-TEMPO, we found that rotenone-induced mitochondrial H2O2 also in turn elevated [Ca2+]i level, thereby stimulating CaMKII, leading to inhibition of mTOR pathway and induction of neuronal apoptosis. Expression of wild type mTOR or constitutively active S6K1, or silencing 4E-BP1 strengthened the inhibitory effects of catalase, Mito-TEMPO, BAPTA/AM or EGTA on rotenone-induced [Ca2+]i elevation, CaMKII phosphorylation and neuronal apoptosis. Together, the results indicate that the crosstalk between Ca2+ signaling and mitochondrial H2O2 is required for rotenone inhibition of mTOR-mediated S6K1 and 4E-BP1 pathways. Our findings suggest that how to control over-elevation of intracellular Ca2+ and overproduction of mitochondrial H2O2 may be a new approach to deal with the neurotoxicity of rotenone. PMID- 26859574 TI - Role of heme oxygenase-1 in the pathogenesis and tumorigenicity of Kaposi's sarcoma-associated herpesvirus. AB - Kaposi's Sarcoma-associated Herpesvirus (KSHV) is the etiologic agent of several malignancies, including Kaposi's Sarcoma (KS), which preferentially arise in immunocompromised patients such as HIV+ subpopulation and lack effective therapeutic options. Heme oxygenase-1 (HO-1) has been reported as an important regulator of endothelial cell cycle control, proliferation and angiogenesis. HO-1 has also been found to be highly expressed in KSHV-infected endothelial cells and oral AIDS-KS lesions. We previously demonstrate that the multifunctional glycoprotein CD147 is required for KSHV/LANA-induced endothelial cell invasiveness. During the identification of CD147 controlled downstream genes by microarray analysis, we found that the expression of HO-1 is significantly elevated in both CD147-overexpressing and KSHV-infected HUVEC cells when compared to control cells. In the current study, we further identify the regulation of HO 1 expression and mediated cellular functions by both CD147 and KSHV-encoded LANA proteins. Targeting HO-1 by either RNAi or the chemical inhibitor, SnPP, effectively induces cell death of KSHV-infected endothelial cells (the major cellular components of KS) through DNA damage and necrosis process. By using a KS like nude mouse model, we found that SnPP treatment significantly suppressed KSHV induced tumorigenesis in vivo. Taken together, our data demonstrate the important role of HO-1 in the pathogenesis and tumorigenesis of KSHV-infected endothelial cells, the underlying regulatory mechanisms for HO-1 expression and targeting HO 1 may represent a promising therapeutic strategy against KSHV-related malignancies. PMID- 26859573 TI - Tumor-targeting Salmonella typhimurium A1-R in combination with doxorubicin eradicate soft tissue sarcoma in a patient-derived orthotopic xenograft (PDOX) model. AB - A patient with high grade undifferentiated pleomorphic soft-tissue sarcoma from a striated muscle was grown orthotopically in the right biceps femoris muscle of mice to establish a patient-derived orthotopic xenograft (PDOX) model. Twenty PDOX mice were divided into 4 groups: G1, control without treatment; G2, Salmonella typhimurium (S. typhimurium)A1-R administered by intratumoral (i.t.) injection once a week for 4 weeks; G3, doxorubicin (DOX) administered by intraperitoneal (i.p.) injection once a week for 4 weeks; G4, S. typhimurium A1-R (i.t.) administered once a week for 2 weeks followed by i.p. doxorubicin once a week for 2 weeks. On day 25 from the initiation of treatment, tumor volume in G2, G3, and G4 was significantly lower than G1. Mice found without gross tumor included one mouse (20%) in G2; one mouse (20%) in G3; and 3 mice (60%) in G4. Body weight loss did not significantly differ between the 3 treated groups or from the untreated control. Histological examination revealed eradication of tumor only in G4 where mice were treated with S. typhimurium A1-R followed by DOX. Our present study indicates future clinical potential of combining S. typhimurium A1-R with chemotherapy such as DOX for soft tissue sarcoma patients. PMID- 26859575 TI - The sonic hedgehog signaling pathway stimulates anaplastic thyroid cancer cell motility and invasiveness by activating Akt and c-Met. AB - The sonic hedgehog (Shh) pathway is highly activated in thyroid neoplasms and promotes thyroid cancer stem-like cell phenotype, but whether the Shh pathway regulates thyroid tumor cell motility and invasiveness remains unknown. Here, we report that the motility and invasiveness of two anaplastic thyroid tumor cell lines, KAT-18 and SW1736, were inhibited by two inhibitors of the Shh pathway (cyclopamine and GANT61). Consistently, the cell motility and invasiveness was decreased by Shh and Gli1 knockdown, and was increased by Gli1 overexpression in KAT-18 cells. Mechanistic studies revealed that Akt and c-Met phosphorylation was decreased by a Gli1 inhibitor and by Shh and Gli1 knockdown, but was increased by Gli1 overexpression. LY294002, a PI-3 kinase inhibitor, and a c-Met inhibitor inhibited the motility and invasiveness of Gli1-transfected KAT-18 cells more effectively than the vector-transfected cells. Knockdown of Snail, a transcription factor regulated by the Shh pathway, led to decreased cell motility and invasiveness in KAT-18 and SW1736 cells. However, key epithelial-to mesenchymal transition (EMT) markers including E-cadherin and vimentin as well as Slug were not affected by cyclopamine and GANT61 in either SW1736 or WRO82, a well differentiated follicular thyroid carcinoma cell line. Our data suggest that the Shh pathway-stimulated thyroid tumor cell motility and invasiveness is largely mediated by AKT and c-Met activation with little involvement of EMT. PMID- 26859577 TI - Contrasting Responses to Harvesting and Environmental Drivers of Fast and Slow Life History Species. AB - According to their main life history traits, organisms can be arranged in a continuum from fast (species with small body size, short lifespan and high fecundity) to slow (species with opposite characteristics). Life history determines the responses of organisms to natural and anthropogenic factors, as slow species are expected to be more sensitive than fast species to perturbations. Owing to their contrasting traits, cephalopods and elasmobranchs are typical examples of fast and slow strategies, respectively. We investigated the responses of these two contrasting strategies to fishing exploitation and environmental conditions (temperature, productivity and depth) using generalized additive models. Our results confirmed the foreseen contrasting responses of cephalopods and elasmobranchs to natural (environment) and anthropogenic (harvesting) influences. Even though a priori foreseen, we did expect neither the clear-cut differential responses between groups nor the homogeneous sensitivity to the same factors within the two taxonomic groups. Apart from depth, which affected both groups equally, cephalopods and elasmobranchs were exclusively affected by environmental conditions and fishing exploitation, respectively. Owing to its short, annual cycle, cephalopods do not have overlapping generations and consequently lack the buffering effects conferred by different age classes observed in multi-aged species such as elasmobranchs. We suggest that cephalopods are sensitive to short-term perturbations, such as seasonal environmental changes, because they lack this buffering effect but they are in turn not influenced by continuous, long-term moderate disturbances such as fishing because of its high population growth and turnover. The contrary would apply to elasmobranchs, whose multi-aged population structure would buffer the seasonal environmental effects, but they would display strong responses to uninterrupted harvesting due to its low population resilience. Besides providing empirical evidence to the theoretically predicted contrasting responses of cephalopods and elasmobranchs to disturbances, our results are useful for the sustainable exploitation of these resources. PMID- 26859576 TI - Targeting hypoxic response for cancer therapy. AB - Hypoxic tumor microenvironment (HTM) is considered to promote metabolic changes, oncogene activation and epithelial mesenchymal transition, and resistance to chemo- and radio-therapy, all of which are hallmarks of aggressive tumor behavior. Cancer cells within the HTM acquire phenotypic properties that allow them to overcome the lack of energy and nutrients supply within this niche. These phenotypic properties include activation of genes regulating glycolysis, glucose transport, acidosis regulators, angiogenesis, all of which are orchestrated through the activation of the transcription factor, HIF1A, which is an independent marker of poor prognosis. Moreover, during the adaptation to a HTM cancer cells undergo deep changes in mitochondrial functions such as "Warburg effect" and the "reverse Warburg effect".This review aims to provide an overview of the characteristics of the HTM, with particular focus on novel therapeutic strategies currently in clinical trials, targeting the adaptive response to hypoxia of cancer cells. PMID- 26859578 TI - Five-year outpatient programme that provided children with continuous behavioural obesity treatment enjoyed high success rate. AB - AIM: Results from long-time follow-up of obesity treatment in early childhood are lacking. We investigate long-term continuous behavioural childhood obesity treatment and factors of importance for treatment effect. METHOD: A five-year longitudinal retrospective controlled study of children aged five to 13 years in obesity treatment, divided into three groups depending on age at start of treatment. Outcome is presented as change in degree of obesity, body mass index standard deviation score (BMI SDS), change in weight status and decrease of >=0.5 BMI SDS units, in relation to a age-matched obese comparison group. RESULTS: In total, 220 children (46% females) were included. After five years of treatment, the decrease in BMI SDS was significant in all age groups with the largest effect in age group 4-6 years. Compared to the comparison group (n = 369), the decline in BMI SDS was greater (p = 0.001). After five years of treatment, 48% of the patients were cured from their obesity and 72% reached a decline of 0.5 BMI SDS units. Age at start of treatment was the only factor affecting treatment efficacy. CONCLUSION: The ability to reach a significant weight loss in a paediatric outpatient clinic is promising through a long-term behavioural obesity treatment. PMID- 26859579 TI - Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer. AB - BACKGROUND: Cytokines and chemokines in the tumor microenvironment drive metastatic development and their serum levels might mirror the ongoing inflammatory reaction at the tumor site. Novel highly sensitive tools are needed to identify colorectal cancer patients at high risk of recurrence that should be more closely monitored during post-surgical follow up. Here we study whether circulating inflammatory markers might be used to predict recurrence in CRC patients. METHODS: Circulating levels of the inflammatory cytokines IL-1, IL-6, IL-10, TNFalpha, CCL2, CXCL8, VEGF and the acute phase protein Pentraxin-3 were measured by ELISA in preoperative serum samples prospectively collected from a cohort of sixty-nine patients undergoing surgical resection for stage 0-IV CRC and associated with post-operative disease recurrence. RESULTS: Cox multivariate analysis showed that combined high levels (>=ROC cut off-value) of CXCL8, VEGF and Pentraxin3 were associated with increased risk of disease recurrence [HR: 14.28; 95%CI: (3.13-65.1)] independently of TNM staging. Kaplan-Meier analysis showed that CXCL8, VEGF and Pentraxin3 levels were significantly associated with worse survival (P<0.001). CONCLUSIONS: Circulating inflammatory mediators efficiently predicted postoperative recurrence after CRC surgery. Therefore, this study suggest that their validation in large-scale clinical trials may help in tailoring CRC post-surgical management. PMID- 26859581 TI - Pancreas transplantation in older patients is safe, but patient selection is paramount. AB - Pancreas transplant outcomes have progressively improved. Despite this, some centers have continued to employ historical age limits for pancreas transplant candidates. We sought to determine the importance of chronological age in determining patient and graft survival rates after pancreas transplantation. A single-center, retrospective study of adult, deceased donor simultaneous pancreas and kidney (SPK) and solitary pancreas transplants (SP, including pancreas transplant alone and pancreas after kidney transplants) in recipients >= 55 years (55 + ), occurring between July 1, 1999, and June 30, 2012, was performed. Seven hundred and forty patients underwent pancreas transplantation, of which 28 patients were 55 + . Patient survival was comparable for younger and older pancreas transplant recipients. Both non-death-censored and death-censored pancreatic graft survival rates were similar in younger and in older patients. Patients aged 45-54 and those aged 55 + had more frequent cardiovascular events than younger pancreas transplant recipients. There was no difference in renal graft survival for SPK patients when compared with diabetic kidney transplant alone recipients aged 55 years and older. Older pancreas transplant recipients had acceptable long-term patient and graft survival rates, although complications may occur. Chronological age alone should not exclude a patient for pancreas transplant candidacy. PMID- 26859582 TI - Denosumab-related osteonecrosis of the jaws: successful management with a conservative surgical approach. AB - Denosumab-related osteonecrosis of the jaws (DRONJ) is a recently described entity that shares many common clinical and radiological features with bisphosphonate-related osteonecrosis of the jaws (BRONJ). The aim of the present study is to report a case of DRONJ affecting the anterior mandible of a 58-year old male treated with denosumab to prevent skeletal-related events associated with prostate cancer. Conservative surgery in conjunction with antibiotic therapy and discontinuation of denosumab use were effective in managing the condition and the patient remains free of clinical and radiological changes after a 38 month follow-up. PMID- 26859583 TI - The complex etiology of schizophrenia - general state of the art. AB - The etiology of schizophrenia is complex. The aim of this article is to present a global view of the causes of schizophrenia and their interconnectivity. Recent genetic research into schizophrenia is based on genome-wide association studies, the assessment of DNA copy number variations, and the concept of endophenotypes. A lot of suspected genes have already been identified, mostly relating to neurodevelopment, neuroplasticity, immunology and neuroendocrinology. Gene environment interactions (G*E) reflect genetic variation in susceptibility to the environment. Psychosocial stress and cannabis abuse seem to be the most important environmental factors in schizophrenia etiology. Epigenetic mechanisms, particularly DNA methylation, histone modifications, and non-coding RNAs are the most important linking factor among the genetic and prenatal environmental variables in the etiology of schizophrenia. Postnatal risk factors (e.g., stress, urbanicity, cannabis use) may also affect the risk of schizophrenia via the potentiation of vulnerable brain pathways. Many questionable issues pertaining to G*E assessment of schizophrenia still persist and relate to the exact assessment of environmental agents as well as psychopathology. In future research concerning G*E in schizophrenia, the study samples should be adequately large, schizophrenia endophenotypes should be involved, prospective studies should be supported, environmental causative factors as well as psychopathology should be assessed in a quantitative way, the multiple interactions among the variety of environmental and genetic variables should be evaluated, and epigenetic factors should not be neglected. The EU-GEI project of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (2010-2015) may become a milestone in the schizophrenia G*E research. PMID- 26859584 TI - New molecular aspects of endometrial carcinoma. AB - Endometrial cancer is the most commonly diagnosed gynecological cancer and its incidence is increasing worldwide. The number of patients with this disease is likely to continue to grow, including younger patients. It is a complex disease driven by abnormal genetic and epigenetic alterations, as well as environmental factors. Many endometrial cancers show estrogen-dependent proliferation. The carcinogenic mechanisms are unknown or not completely explained beyond mutations of single oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include imbalance between endometrial proliferation by unopposed estrogen and the mismatch repair (MMR) system; rmethylation changes and mutation of genes. Epigenetic changes resulting in aberrant gene expression are dynamic and modifiable features of many cancer types. A significant epigenetic change is aberrant DNA methylation. In this review, we review evidence on the role of different changes in relation to endometrial carcinogenesis. Carcinogenic mechanisms of endometrial cancer involve both genetic and epigenetic changes. Determination of the detailed carcinogenic mechanisms will be useful for prevention and diagnosis of endometrial cancer, risk assessment, and development of new treatment strategies targeting genes. PMID- 26859585 TI - Quality of life in women after menopause. AB - Over the last few years prolonging of an average life span of women in the majority of population has been observed. The average age of life span of a Polish woman was 81 years in 2012. The menopause takes place more or less in the 51st year of age at the average. Thus, the period after menopause is around 30 years long, which is over one third of a whole life span. The last menstruation is preceded by many characteristic hormonal changes which lead to inhibiting ovaries' hormonal activity which is described as premenopause. Changes accompanying the menopause concern first of all a decrease in ovarian synthesis of oestrogens, progesterone, ovarian androgens (testosterone and androsterone), and of adrenal dehydroepiandrosterone and its sulphate. Climacteric symptoms and frequent occurrence of many systemic diseases negatively affecting one's mental condition and self-esteem may lead to depression and worsening of a relationship with a partner and with an environment, which, in turn, significantly worsens the quality of life. Maintaining the quality of life after menopause is enhanced both by pharmacological treatment, namely hormone therapy and by alternative methods: the appropriate lifestyle or active sexual life. A gynaecologists play an important role in maintaining the quality of life, because they help the woman take the decision of introducing hormonal therapy. PMID- 26859586 TI - Acquired generalized lipodystrophy in a young lean Chinese girl. Case Report. AB - Lipodystrophies is a really rare group of diseases characterized by altered body fat amount and/or repartition and serious insulin resistance.We reported a lean Chinese girl with acquired generalized lipodystrophy, who had a long history of poorly controlled diabetes mellitus (DM) despite with extremely high dose insulin (6 u/kg/d) therapy, combined with severe hypertriglyceridemia and acanthosis nigricans. The differential diagnosis of Lipodystrophies should be considered in lean patients presenting with early onset DM, combined with serious insulin resistance. PMID- 26859587 TI - The first description of metyrapone use in severe Cushing Syndrome due to ectopic ACTH secretion in an infant with immature sacrococcygeal teratoma. Case Report. AB - Cushing syndrome due to ectopic secretion of ACTH in infants is rare. The treatment of choice is radical resection of the tumour in combination with pre operative chemotherapy using steroidogenesis inhibitors if necessary. If radical surgery is not possible, palliative treatment of hypercortisolemia is recommended. The most frequently used drug in infants is ketoconazole. Experience with the use of metyrapone is poor. We report an 8-month-old female infant with congenital immature sacrococcygeal teratoma secreting AFP, beta hCG and ACTH who had undergone non-radical resection of the tumour mass and was receiving standard risk chemotherapy (vinblastine, bleomycin, and cisplatin). The infant initially presented at the age of 6 months with ACTH-dependent Cushing syndrome (cortisol and ACTH level 325 ng/mL, 112 pg/mL respectively). Treatment with ketoconazole was initiated with a dose of 600 mg/day. Due to its ineffectiveness metyrapne was added in increasing dosages, up to 1,500 mg/day. In addition the schema of chemotherapy was changed (adriamycin, bleomycin, carboplatin), which resulted in normalization of cortisol levels and blood pressure. There were no metyrapone side effects during the treatment period. We can conclude that treatment with metyrapone at a dose of 1500 mg/day might be effective and safe in infants with Cushing syndrome. PMID- 26859588 TI - Prenatal three-dimensional sonographic findings associated with fetal defecation. Case Report. AB - Routine ultrasonography examination may miss fetal defecation and if seen it can be a source of misinterpretation which can lead to a wrong diagnose and management of pregnancy. We report two rare cases of fetal defecation in the second trimester and we describe 3D sonographic findings associated with this condition. PMID- 26859589 TI - Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy. AB - OBJECTIVE: The aim of the liposoluble vitamin solution in the DBM formulation is to enhance the biovailability, the stability, the half-life and the therapeutic efficacy of the components without resorting to excessive or toxic doses. METHOD: The DBM vitamin solution contains 0.5 grams of vitamin A palmitate ester, 0.5 grams of all-trans-retinoic acid (ATRA), and 2 grams of beta-Carotene, in 1 000 grams of vitamin E acetate ester which stabilizes the other components, protecting them from oxidation. The solution is administered before meals at the dose of 90 to 150 mg per kg of body weight. The quantities have a determining value for a pharmacological result. No phenomena of overdose and/or toxicity have ever been detected in the tens of thousands of people who have used the solution with this formulation and dosage. RESULTS: Thanks to the synergic effect of the components and their antioxidant, free antiradical, cell-membrane stabilizing, differentiating and cytostatic properties, this solution has constantly produced positive therapeutic responses. Favourable effects have been observed in the prevention and treatment of neoplastic diseases, as well as on immunity, physiological growth, trophism and functionality of tegumental, respiratory, digestive, urogenital and exocrine gland epithelia. A significant antidegenerative effect has also been observed in pretumoral stages. Studies have been published reporting 754 cases of various types of tumor which have greatly benefited from the use of this vitamin solution synergically and factorially reinforced by the other components of the DBM, such as Melatonin, Vitamins D and C, D2 receptor agonists, and GH inhibitors like Somatostatina and analogs. CONCLUSIONS: In view of the documented results achieved, we believed it useful to provide the scientific community with the details of the formulation, preparation, posology, rationale, mechanism of action, biochemical, molecular and physiological bases, indications and clinical findings relating to the DBM liposoluble vitamin solution. PMID- 26859590 TI - The role of antithyroglobulin, antiperoxidase and anti-TSH receptor autoantibodies in amiodarone-induced thyrotoxicosis and amiodarone-induced hypothyroidism (A two-center study). AB - OBJECTIVE: It has been reported that patients experiencing side effects of amiodarone (AM) therapy, such as amiodarone-induced thyrotoxocosis (AIT) or amiodarone-induced hypothyroidism (AIH), have changes in serum concentrations of anti-TSH receptor (TSHR), antithyroglobulin (Tg), and antiperoxidase (TPO) autoantibodies (Abs). The purpose of our study was to identify and analyze the changes in levels of listed antibodies in patients with several thyroid disorders. METHODS: 280 patients from two centers in Poland were included. Titers of TSHR-Abs, TPO-Abs and Tg-Abs were analyzed retrospectively in the following groups of patients: A - euthyroid patients with a history of hyperthyroidism prior to re-administration of AM; B - patients with AIT who discontinued the AM therapy; C - patients with AIT chronically treated with AM; D - hypothyroid patients. RESULTS: Serum Tg-Abs were not elevated in any of the studied groups. However, there were significant differences between A and B and also D and other groups (p<0.05). TPO-Abs titers were not elevated in most cases, there were no significant differences between groups. The serum titers of TSHR-Abs were not elevated in any group. We found statistically significant differences between B and D, C and other groups (p<0.05). CONCLUSIONS: Regardless of the statistically significant differences observed for Tg-Abs and TSHR-Abs levels, this observation have a limited clinical applicability. In almost all cases we observed normal to slightly increased titers of TPO-Abs, Tg-Abs, TSHR-Abs. Discontinuation or continuation of AM therapy had no influence on autoantibody titers. Furthermore, we found it impossible to differentiate between the type I and II of AIT based on autoantibody titers. PMID- 26859591 TI - Hippocampal but not amygdalar volume loss in narcolepsy with cataplexy. AB - OBJECTIVE: Narcolepsy with cataplexy (NC) and narcolepsy without cataplexy (NwoC) are lifelong neurological disorders characterized primarily by excessive daytime sleepiness. Emotional events such as laughter are a trigger of cataplexy in NC. METHODS: We compared the volumes of key limbic structures, the amygdala and hippocampus, in 53 NC, 23 NwoC and 37 control subjects. MRI volumetry was performed in FreeSurfer (FS) and by manual delineation. RESULTS: We found no differences in amygdalar volume in the three groups, however, hippocampal volume was significantly smaller in the NC group than in other groups. Amygdalar and hippocampal volumes assessed by FS were significantly greater, but strong positive correlation between manual and FS results were observed. Thus, both methods are suitable for amygdalar and hippocampal volumetry. PMID- 26859593 TI - Overexpression of miR-21 and miR-122 in preeclamptic placentas. AB - OBJECTIVE: Preeclampsia is a pregnancy-associated disease with the impact of genetic, epigenetic and environmental factors. Increased apoptosis was observed in cells from preeclamptic placentas. MicroRNAs are involved in the regulation of apoptosis and are abundant in placenta. In this study, we focused on the analysis of differential gene expression of apoptosis-associated miRNAs in preeclamptic placenta samples compared to the samples obtained from healthy pregnant women. METHODS: MicroRNA was extracted from placental samples of patients with preeclampsia and physiological course of the pregnancy. The gene expression of miR-155, miR-122 and miR-21 in placenta and control samples was estimated by relative quantitation (RQ) using TaqMan probes, normalized against RNU44. The RQ mean values were statistically evaluated by Man-Whitney test. RESULTS: Using the relative gene expression analysis, we could observe a significant increase in gene expression of miR-155 (p<0.001), miR-21 (p<0.0001) and miR-122 (p<0.01) in preeclamptic placentas. CONCLUSION: The apoptosis-associated miRNAs miR-21 and miR-122 are dysregulated in the term preeclamptic placentas. The increased miRNA expression suggest the downregulation of potential targets mRNAs, which can contribute to the pathogenesis of preeclampsia. The identification of their targets in placenta will improve our understanding of their role in preeclampsia. PMID- 26859592 TI - Cerebrospinal fluid oxytocin correlated with peripheral ALT and AST in Chinese female subjects. AB - OBJECTIVE: Oxytocin (OT) is primarily synthesized in the paraventricular nucleus of the hypothalamus and supraoptic nucleus of the hypothalamus in the central nervous system and exhibits a wide spectrum of central and peripheral activities. OT is involved in lipid metabolism and glucose homeostasis and plays a protective role against liver damage. METHODS: In this study, we investigated whether CSF OT levels correlates with peripheral glucose, lipid profiles, and/or liver enzymes in Chinese subjects. Sixty-nine subjects (n=36 males; n=33 females) who were recruited from Beijing Jishuitan Hospital participated in the study. Their levels of CSF OT and peripheral parameters were assayed by radioimmunoassay and continuous monitoring assay, respectively. RESULTS: There was no significant difference in CSF OT levels between males (53.09+/-6.88 nmol/mL) and females (52.34+/-6.87 nmol/mL), and no correlation found between CSF OT levels and peripheral glucose and lipid profiles. Significant negative correlation was observed between CSF OT levels and peripheral ALT and AST concentration in females but not in males. CONCLUSION: Our results support the physiological role of neuropeptides acting on brain sites to regulate liver enzymes, and shed new light on the brain-liver interaction. PMID- 26859594 TI - Enhanced liver fibrosis (ELF) test in obese children with ultrasound-proven liver steatosis. AB - OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) in obese children is a diagnostic challenge. The enhanced liver fibrosis test (ELF) based on the combination of serum concentration of hyaluronic acid (HA), aminoterminal propeptide of type III procollagen (PIIINP), tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1) was developed as a noninvasive diagnostic tool for estimation of degree of liver fibrosis. The aim of our study was to investigate the performance of ELF test in obese children with ultrasound-proven steatosis in order assess the possibility of early detection of fibrotic changes in liver structure. MATERIAL AND METHODS: 58 obese (BMI >95th percentile) children, 27 male (mean age 13.9+/-2.65 years) and 31 female (mean age 13.82+/ 2.64 years). Based on the liver ultrasound (US) examination results two groups of obese children were studied: group with steatosis (N=20, 8/12 M/F, mean age 14.2+/-1.90 years, BMI 32.9+/-5.60 kg/m2) and group with normal liver US (n=38, 19/19 M/F, mean age 13.7+/-2.94 years, BMI 30.4+/-4.67 kg/m2). Serum activity of aminotransferases (AST, ALT) and lactate dehydrogenase (LDH), and gamma-glutamyl transpeptidase (GGT), and ELF test (HA, PIIINP, and TIMP-1 were analyzed. RESULTS: Children with liver steatosis presented with significantly higher AST (34.1 vs. 25.6 U/L), ALT (43.4 vs. 32 U/L), LDH (427.5 vs. 361.3 U/L), GGT (30.7 vs. 18.9 U/L). The ELF test value was also significantly higher in that group (8.98 vs. 8.49). Nevertheless no combination of measured parameters with ELF test value show better diagnostic value for differentiation between children with and without steaotosis. CONCLUSION: ELF test cannot be used for assessment of steatosis in obese children. PMID- 26859596 TI - Executions and scientific anatomy. AB - The very word "anatomy" tells us about this branch's connection with dissection. Studies of anatomy have taken place for approximately 2.300 years already. Anatomy's birthplace lies in Greece and Egypt. Knowledge in this specific field of science was necessary during surgical procedures in ophthalmology and obstetrics. Embalming took place without public disapproval just like autopsies and manipulation with relics. Thus, anatomical dissection became part of later forensic sciences. Anatomical studies on humans themselves, which needed to be compared with the knowledge gained through studying procedures performed on animals, elicited public disapprobation and prohibition. When faced with a shortage of cadavers, anatomists resorted to obtaining bodies of the executed and suicide victims - since torture, public display of the mutilated body, (including anatomical autopsy), were perceived as an intensification of the death penalty. Decapitation and hanging were the main execution methods meted out for death sentences. Anatomists preferred intact bodies for dissection; hence, convicts could thus avoid torture. This paper lists examples of how this process was resolved. It concerns the manners of killing, vivisection on people in the antiquity and middle-ages, experiments before the execution and after, vivifying from seeming death, experiments with galvanizing electricity on fresh cadavers, evaluating of sensibility after guillotine execution, and making perfect anatomical preparations and publications during Nazism from fresh bodies of the executed. PMID- 26859595 TI - Psychometric properties of the Czech version of the Beck Anxiety Inventory - comparison between diagnostic groups. AB - OBJECTIVE: Beck anxiety inventory (BAI) is widely used self-rating questionnaire evaluating the severity of anxiety symptoms. The aim of our study was to confirm validity and reliability of Czech version of BAI, identify cut-off points and prove sensitivity to measure improvement after therapy. METHODS: The patients selected for the study were treated in the department of psychiatry, University Hospital Olomouc between January 2008 and 2014. Patients meeting criteria for anxiety, or depressive disorder were involved. RESULTS: 789 patients and 284 healthy controls agreed to participate in the study. Czech version of Beck anxiety inventory proved high internal consistency (alpha=0.92) and good test retest reliability over one week (BAI seems to be independent of other used scales - Beck depression inventory and the Clinical Global Impression. BAI is also sensitive to measure change after therapy. CONCLUSION: Czech version of BAI was found to have enough internal stability and test-retest reliability same as the original version. It may also be useful to detect improvement after therapy. PMID- 26859597 TI - Stromal Cell-Derived Factor-1-3'A Polymorphism Favors HIV-1 Infection in Mexican Women. AB - OBJECTIVE: To evaluate the association of the stromal cell-derived factor-1 (SDF1)-3'A polymorphism to HIV-1 infection, CD4+ T-lymphocyte counts, and viral load levels in a northwestern Mexican population. METHODS: We investigated allele and genotype frequencies of the SDF1-3'A polymorphism in 634 mestizo individuals from Northwest Mexico (204 HIV-1 infected persons, 256 uninfected blood donors, and 174 uninfected female sex workers) by the PCR- RFLP method and compared them using a x(2) test. We also searched for correlations between the polymorphism and CD4+ T lymphocyte and viral load counts. RESULTS: No differences were observed in the frequencies of alleles and genotypes between patients and controls. However, in female patients we found a significantly increased prevalence of both the A allele and GA heterozygous genotype compared to male patients, female blood donors, and female sex workers. CONCLUSION: Here we describe the association of the SDF1-3'A polymorphism with HIV-1 infection only in women, but not to CD4+ T lymphocyte categories, viral load levels in patients with HIV-1/AIDS, or to exposure levels in female sex workers. PMID- 26859599 TI - Prolonged Hyperbilirubinemia in a Neonate with a Novel Mutation in the UDP glucuronosyltransferase 1A1 Gene. AB - The total bilirubin value of a male infant was 385 MUmol/l on day 5. Liver function test results were normal and there was no evidence of sepsis and no hemolysis reaction. Phototherapy was administered and on day 8 the patient's total bilirubin level was 255 MUmol/l. Intermittent episodes of hyperbilirubinemia occurred without phototherapy, with the total bilirubin level reaching 335 MUmol/l on day 19. A 3-day regimen of phenobarbital was administered and on day 24 his total bilirubin level was 180 MUmol/l. The patient was discharged. At the age of 2 months, the total bilirubin value was 27 MUmol/l. His direct bilirubin value was <15% of total bilirubin in every determination. A family study of the UDP-glucuronosyltransferase(UGT)1A1 gene showed that the infant carries a homozygous mutation at nucleotide -3279 plus compound heterozygous mutations at nucleotides 782 and 1091. The mutation at nucleotide 782 is a novel finding. Gilbert's syndrome was diagnosed. PMID- 26859598 TI - Association of ISMav6 with the Pattern of Antibiotic Resistance in Korean Mycobacterium avium Clinical Isolates but No Relevance between Their Genotypes and Clinical Features. AB - The aim of this study was to genetically characterize clinical isolates from patients diagnosed with Mycobacterium avium lung disease and to investigate the clinical significance. Multi-locus sequencing analysis (MLSA) and pattern of insertion sequence analysis of M. avium isolates from 92 Korean patients revealed that all isolates were M. avium subspecies hominissuis. In hsp65 sequevar analysis, codes 2, 15, and 16 were most frequently found (88/92) with similar proportions among cases additionally two isolates belonging to code N2 and an unreported code were identified, respectively. In insertion element analysis, all isolates were IS1311 positive and IS900 negative. Four of the M. avium subsp. hominissuis isolates did not harbor IS1245 and 1 of the M. avium isolates intriguingly harbored DT1, which is thought to be a M. intracellulare-specific element. M. avium subsp. hominissuis harboring ISMav6 is prevalent in Korea. No significant association between clinical manifestation and treatment response has been found in patients with the hsp65 code type and ISMav6, indicating that no specific strain/genotype among M. avium subsp. hominissuis organisms was a major source of M. avium lung disease. Interestingly, the presence of ISMav6 was correlated with greater resistance to moxifloxacin. Conclusively, the genotype of Korean M. avium subsp. hominissuis isolates is not a disease determinant responsible for lung disease and specific virulent factors of M. avium subsp. hominissuis need to be investigated further. PMID- 26859600 TI - Hypogonadism in young men treated for cancer. AB - An ever-increasing proportion of young males treated for cancer are cured. Therefore, one of the major challenges of modern Clinical Oncology is to ensure good quality of life. Cancer disease per se as well as cancer treatment may have a negative impact on androgen production, thereby leading to subclinical or clinically overt hypogonadism. Since the symptoms of androgen deficiency are rather unspecific, it is important that reproductive hormone levels be checked in young men who have been treated for cancer. As androgen deficiency in men is associated with increased long-term risk of osteoporosis as well as cardiovascular and metabolic disease, those cancer survivors who present with signs of insufficient androgen production should be followed and preventive as well as therapeutic measures, including androgen replacement therapy, should be applied according to the current guidelines. PMID- 26859601 TI - The Sertoli cell: Novel clinical potentiality. AB - The Sertoli cell is important for endocrine and paracrine control of spermatogenesis. Functions attributed to Sertoli cells are: (1) supportive and trophic functions for the cells of the seminiferous epithelium, (2) transport of mature spermatids towards the lumen of seminiferous tubules, (3) secretion of androgen binding protein, (4) production of substances with endocrine or paracrine action for spermatogenesis control and (5) interaction with intertubular endocrine Leydig cells. Inhibin B and anti-Mullerian hormone (AMH) are glycoproteins belonging to the transforming growth factor beta (TGF-beta) superfamily; they are produced almost exclusively by the Sertoli cells and have been proposed as direct markers of their function and indirect markers of spermatogenesis. Serum inhibin B and AMH concentrations seem to constitute additional diagnostic parameters in male subfertility as they reflect Sertoli cell function. Stimulated concentrations of serum inhibin B and AMH do not add clinically relevant information in subfertile men compared to basal concentrations of these hormones. Serum inhibin B and AMH concentrations correlate with testicular histology/cytology but are not superior to FSH as predictors of the presence of sperm in testicular sperm extraction (TESE)/fine needle aspiration (FNA) biopsy in men with azoospermia. PMID- 26859602 TI - The impact of adipose tissue-derived factors on the hypothalamic-pituitary gonadal (HPG) axis. AB - Adipose tissue produces factors, including adipokines, cytokines and chemokines which, when released, systemically exert endocrine effects on multiple tissues thereby affecting their physiology. Adipokines also affect the hypothalamic pituitary-gonadal (HPG) axis both centrally, at the hypothalamic-pituitary level, and peripherally acting on the gonads themselves. Among the adipokines, leptin, adiponectin, resistin, chemerin and the peptide kisspeptin have pleiotropic actions on the HPG axis affecting male and female fertility. Furthermore, adipokines and adipose tissue-produced factors readily affect the immune system resulting in inflammation, which in turn impact the HPG axis, thus evidencing a link between metabolic inflammation and fertility. In this review we provide an overview of the existing extensive bibliography on the crosstalk between adipose tissue-derived factors and the HPG axis, with particular focus on the impact of obesity and the metabolic syndrome on gonadal function and fertility. PMID- 26859604 TI - Fabrication of Metal-Deposited Indium Tin Oxides: Its Applications to 385 nm Light-Emitting Diodes. AB - We report performance improvements in near-ultraviolet (NUV) light-emitting diodes (LEDs) using various metal-doped indium tin oxide (ITO/metals). Metals with an orbital energy gap greater than that of an In atom (e.g., Ti, Ga, Ge, and Al) are deposited on ITO, and subsequent annealing is performed to improve optical transmittance of ITO due to effective bandgap increase via the linear combination of atomic orbitals, as well as electrical conductivity; thus, current spreading via metal-doping effect at the surface of ITO. As a result, the ITO/metals (annealed at 550 degrees C, 1 min) exhibit 90.5-94.7% transmittance at 385 nm and a specific contact resistance of 2.1-3.0 * 10(-3) Omega cm(2), whereas the reference ITOs exhibit 76.5-89.5% and 3.2-4.5 * 10(-3) Omega cm(2), respectively. Compared to NUV LEDs using conventional ITO (60 nm), the InGaN/AlGaInN NUV LED using ITO (110 nm)/metal (3 nm) on average exhibits a 70% increase in light output power at 100 mA and a 2% decrease in forward voltage at 20 mA, with more uniform and brighter emission images. We also identified the origin for the improvement by analyzing the surface of ITO/metals using X-ray photoelectron spectroscopy and Auger electron spectroscopy. This approach could offer a simple, effective way to enhance the overall efficiency of conventional NUV LEDs using ITO. PMID- 26859603 TI - Conopeptide-Derived kappa-Opioid Agonists (Conorphins): Potent, Selective, and Metabolic Stable Dynorphin A Mimetics with Antinociceptive Properties. AB - Opioid receptor screening of a conopeptide library led to a novel selective kappa opioid agonist peptide (conorphin T). Intensive medicinal chemistry, guided by potency, selectivity, and stability assays generated a pharmacophore model supporting rational design of highly potent and selective kappa-opioid receptor (KOR) agonists (conorphins) with exceptional plasma stability. Conorphins are defined by a hydrophobic benzoprolyl moiety, a double arginine sequence, a spacer amino acid followed by a hydrophobic residue and a C-terminal vicinal disulfide moiety. The pharmacophore model was supported by computational docking studies, revealing receptor-ligand interactions similar to KOR agonist dynorphin A (1-8). A conorphin agonist inhibited colonic nociceptors in a mouse tissue model of chronic visceral hypersensitivity, suggesting the potential of KOR agonists for the treatment of chronic abdominal pain. This new conorphine KOR agonist class and pharmacophore model provide opportunities for future rational drug development and probes for exploring the role of the kappa-opioid receptor. PMID- 26859606 TI - Concentrations of "legacy" and novel brominated flame retardants in matched samples of UK kitchen and living room/bedroom dust. AB - Concentrations of polybrominated diphenyl ethers (PBDEs), hexabromocyclododecanes (HBCDDs) and 5 novel brominated flame retardants (NBFRs) were measured in paired samples of kitchen and living room/bedroom dust sampled in 2015 from 30 UK homes. BDE-209 was most abundant (22-170,000 ng/g), followed by gamma-HBCDD (1.7-21,000 ng/g), alpha-HBCDD (5.2-4,900 ng/g), beta-HBCDD (2.3-1,600 ng/g), BDE-99 (2.6 1,440 ng/g), BDE-47 (0.4-940 ng/g), decabromodiphenyl ethane (DBDPE) (nd-680 ng/g) and bis(2-ethylhexyl)-3,4,5,6-tetrabromo-phthalate (BEH-TEBP) (2.7-630 ng/g). The concentrations in kitchens and living rooms/bedrooms are moderate compared with previous studies. Concentrations of BDE-209 in living room/bedroom dust were significantly lower and those of DBDPE significantly higher (p < 0.05) compared to concentrations recorded in UK house dust in 2006 and 2007. This may reflect changes in UK usage of these BFRs. All target BFRs were present at higher concentrations in living rooms/bedrooms than kitchens. With the exception of BDE 28, pentabromoethylbenzene (PBEB) and DBDPE, these differences were significant (p < 0.05). No specific source was found that could account for the higher concentrations in living rooms/bedrooms. PMID- 26859605 TI - Socialization and selection effects in the association between weight conscious peer groups and thin-ideal internalization: A co-twin control study. AB - Affiliation with weight conscious peer groups is theorized to increase thin-ideal internalization through socialization processes. However, selection effects could contribute if genetic and/or environmental predispositions lead to affiliation with weight conscious peers. Co-twin control methodology was used to examine socialization and selection effects in 614 female twins (ages 8-15) from the Michigan State University Twin Registry (MSUTR). Thin-ideal internalization and peer group characteristics were assessed via self-report questionnaires. Results suggested the presence of both socialization and selection effects. In terms of socialization, twins who reported increased exposure to weight conscious peers relative to their co-twins had elevated thin-ideal internalization scores, regardless of zygosity. However, associations between weight conscious peers and thin-ideal internationalization within twin pairs were attenuated, suggesting that genetic and shared environmental selection effects also contribute. Findings significantly extend previous work by confirming the presence of socialization processes and highlighting selection processes to be examined in future longitudinal research. PMID- 26859607 TI - Zinc and copper status in childbearing age Tunisian women: Relation to age, residential area, socioeconomic situation and physiologic characteristics. AB - Plasma zinc and copper status of 1689 non pregnant Tunisian women, aged 20-49 years old, was determined by flame atomic absorption spectrometry. A multiple regression was run to predict plasma trace element concentrations from age, BMI, marital status, menopause, education level, professional activity, economic level and area of living. The mean zinc and copper values were similar to those measured among comparable populations in earlier studies. However, a high prevalence of low plasma zinc and copper concentrations was observed assuming that women at childbearing age are at high risk of zinc and copper deficiencies and specific intervention may be considered. In univariate analysis, the mean values of plasma zinc and copper were associated with sitting areas and professional activity. For only plasma copper levels, there was an increase with BMI and parity, and a decrease with increasing schooling level and economic score. After adjustment for all variables, profession and parity showed a significant relationship between plasma levels copper. PMID- 26859608 TI - Occurrence patterns of pharmaceutical residues in wastewater, surface water and groundwater of Nairobi and Kisumu city, Kenya. AB - Emerging organic contaminants have not received a lot of attention in developing countries, particularly Africa, although problems regarding water quantity and quality are often even more severe than in more developed regions. This study presents general water quality parameters as well as unique data on concentrations and loads of 24 pharmaceuticals including antibiotic, anti(retro)viral, analgesic, anti-inflammatory and psychiatric drugs in three wastewater treatment plants, three rivers and three groundwater wells in Nairobi and Kisumu. This allowed studying removal efficiencies in wastewater treatment, identifying important sources of pharmaceutical pollution and distinguishing dilution effects from natural attenuation in rivers. In general, antiretrovirals and antibiotics, being important in the treatment of common African diseases such as HIV and malaria, were in all matrices more prevalent as compared to the Western world. Wastewater stabilization ponds removed pharmaceuticals with an efficiency between 11 and 99%. Despite this large range, a different removal is observed for a number of compounds, as compared to more conventional activated sludge systems. Total concentrations in river water (up to 320 MUg L(-1)) were similar or exceeded concentrations in untreated wastewater, with domestic discharges from slums, wastewater treatment plant effluent and waste dumpsites identified as important sources. In shallow wells situated next to pit latrines and used for drinking water, the recalcitrant antiretroviral nevirapine was measured at concentrations as high as 1-2 MUg L(-1). Overall, distinct pharmaceutical contamination patterns as compared to the Western world can be concluded, which might be a trigger for further research in developing regions. PMID- 26859609 TI - Liquid-Liquid Phase Transition in Nanoconfined Silicon Carbide. AB - We report theoretical evidence of a liquid-liquid phase transition (LLPT) in liquid silicon carbide under nanoslit confinement. The LLPT is characterized by layering transitions induced by confinement and pressure, accompanying the rapid change in density. During the layering transition, the proportional distribution of tetracoordinated and pentacoordinated structures exhibits remarkable change. The tricoordinated structures lead to the microphase separation between silicon (with the dominant tricoordinated, tetracoordinated, and pentacoordinated structures) and carbon (with the dominant tricoordinated structures) in the layer close to the walls. A strong layer separation between silicon atoms and carbon atoms is induced by strong wall-liquid forces. Importantly, the pressure confinement phase diagram with negative slopes for LLPT lines indicates that, under high pressure, the LLPT is mainly confinement-induced, but under low pressure, it becomes dominantly pressure-induced. PMID- 26859610 TI - Evaluating the Psychometric Properties and Responsiveness to Change of 3 Depression Measures in a Sample of Persons With Traumatic Spinal Cord Injury and Major Depressive Disorder. AB - OBJECTIVES: To compare the measurement properties and responsiveness to change of the Patient Health Questionnaire-9 (PHQ-9), the Hopkins Symptom Checklist-20 (HSCL-20), and the Hamilton Depression Rating Scale (HAM-D) in people with spinal cord injury (SCI) diagnosed with major depressive disorder (MDD). DESIGN: Secondary analysis of depression symptoms measured at 6 occasions over 12 weeks as part of a randomized controlled trial of venlafaxine XR for MDD in persons with SCI. SETTING: Outpatient and community settings. PARTICIPANTS: Individuals (N=133) consented and completed the drug trial. Eligibility criteria were age at least 18 years, traumatic SCI, and diagnosis of MDD. INTERVENTIONS: Venlafaxine XR. MAIN OUTCOME MEASURES: Patients completed the PHQ-9 and the HSCL-20 depression scales; clinical investigators completed the HAM-D and the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) Dissociative Disorders, which was used as a diagnostic criterion measure. RESULTS: All 3 instruments were improved with rating scale analysis. The HSCL-20 and the HAM-D contained items that misfit the underlying construct and that correlated weakly with the total scores. Removing these items improved the internal consistency, with floor effects increasing slightly. The HAM-D correlated most strongly with Structured Clinical Interview for DSM-IV Dissociative Disorders diagnoses. Improvement in depression was similar on all outcome measures in both treatment and control groups. CONCLUSIONS: The psychometric properties of the revised depression instruments are more than adequate for routine use in adults with SCI and are responsive to clinical improvement. The PHQ-9 is the simplest instrument with measurement properties as good as or better than those of the other instruments and required the fewest modifications. PMID- 26859611 TI - Fourier transform mid-infrared spectroscopy (FT-MIR) combined with chemometrics for quantitative analysis of dextrin in Danshen (Salvia miltiorrhiza) granule. AB - The granule of Chinese medicine (GCM) is prepared by water-soluble extract of single yinpian (WESY) of herbal medicine, and used as a drug ingredient for clinical formulation. The WESY content or corresponding yinpian amount is the most important parameter in evaluating the quality of GCM. Low WESY content reflects poor GCM. Classical quantitative methods, such as HPLC, cannot fully detect the adulteration by adding characteristic ingredients and less WESY production. GCM is composed of WESY and a high content of specific excipient. The WESY content in the GCM may be indirectly analyzed using mid-infrared spectroscopy (MIR). In this paper, a quantitative method to evaluate the quality of Danshen (Salvia miltiorrhiza) granule (DG) was developed using MIR combined with chemometrics. Appropriate characteristic quantitative regions (CQR) were extracted by selecting the spectral regions corresponding to altered excipient content in DG. The best model of dextrin content determination in DG with low RMSEC of 1.97, low RMSEP of 2.07, and excellent RPD of 5.03 (>5.0) was obtained using partial least-squares (PLS) regression, and validated using accepted values of precision and recovery. The results suggest that FT-MIR combined with PLS is a rapid and valuable analytical tool to determine the WESY in DG based on excipient content. The model enabling indirect calculation of WESY content in GCM represents a reference standard for rapid analysis of other WESYs in GCM industry. PMID- 26859612 TI - A LC-MS/MS method for the determination of stachyose in rat plasma and its application to a pharmacokinetic study. AB - A sensitive, simple and rapid analytical method based on a liquid chromatography tandem mass spetrometry (LC-MS/MS) has been established and validated for the determination of stachyose in rat plasma. Plasma samples were prepared by protein precipitation with acetonitrile. Separation of stachyose and nystose (internal standard, IS) was achieved using acetonitrile-water (55:45, v/v) as the mobile phase at a flow rate of 1 ml/min for 6 min on an Asahipak NH2P-50 4E column with an Asahipak NH2P-50G 4A guard column. Detection and quantification were conducted by LC-MS/MS method in the negative ion mode using multiple reaction monitoring (MRM) transitions at m/z [M-H](-) 665.4->383.1 for stachyose and 665.5->485.0 for IS, respectively. The method was linear over the concentration ranges of 100 30000 ng/ml with a lower limit of quantification (LLOQ) of 100 ng/ml. The intra- and inter- day precision were all within 8.7% and the accuracy ranged from 97.2 108.4% and 98.3-102.4%, respectively. Stability studies indicated that stachyose was stable under short-term, long-term and three freeze-thaw storage conditions. The method was successfully applied to a pharmacokinetic study involving pulmonary administration of micronized Rehmannia glutinosa oligosaccharides (RGOS) to rats. PMID- 26859613 TI - Determination of marbofloxacin in plasma and synovial fluid by ultrafiltration followed by HPLC-MS/MS. AB - A rapid LC-MS/MS method for the determination of marbofloxacin in plasma and synovial fluid is presented in this study. The method uses a rapid sample preparation which only requires an ultrafiltration step with centrifugal filter devices. The optimized procedure allows a minimal need of sample (175 MUL), particularly useful for synovial fluid samples which amount is rather limited; it is simple, rapid and easily applicable providing anyhow a satisfactory clean up, demonstrated by post-infusion experiments. On the other hand to maximize the speed of the analysis an ultrafast chromatographic separation has been obtained by selecting a column of 20 mm; the reduced run-time is suitable for processing numerous samples on a daily basis. Linearity was assessed in the range 5-2500 ng mL(-1); ofloxacin was used as internal standard. LOD and LOQ were respectively 1 and 5 ng/mL. The method was successfully applied to a set of samples generated during an experimental veterinary study. PMID- 26859614 TI - Aggregation of Calcium Silicate Hydrate Nanoplatelets. AB - We study the aggregation of calcium silicate hydrate nanoplatelets on a surface by means of Monte Carlo and molecular dynamics simulations at thermodynamic equilibrium. Calcium silicate hydrate (C-S-H) is the main component formed in cement and is responsible for the strength of the material. The hydrate is formed in early cement paste and grows to form platelets on the nanoscale, which aggregate either on dissolving cement particles or on auxiliary particles. The general result is that the experimentally observed variations in these dynamic processes generically called growth can be rationalized from interaction free energies, that is, from pure thermodynamic arguments. We further show that the surface charge density of the particles determines the aggregate structures formed by C-S-H and thus their growth modes. PMID- 26859615 TI - Expression of the Extracellular Matrix Protein Tenascin-C Varies During Lactation. AB - BACKGROUND: Women diagnosed with pregnancy-associated breast cancer postpartum have a worse prognosis, stage for stage, than other women with breast cancer. The time of breast involution is tumor promotional. The extracellular matrix protein tenascin-C is upregulated during involution in animal models and promotes breast cancer progression. It interacts with transforming growth factor (TGF)beta, which also is involved in breast involution and breast cancer progression. Little is known about the expression of tenascin-C during human breast involution, nor its relationship to TGFbeta. The purpose of this study was to investigate the expression of tenascin-C throughout lactation, as well as its relationship to TGFbeta1 and TGFbeta2. MATERIAL AND METHODOLOGY: Three milk samples from 25 lactating women (transitional, whole, and wean) were collected, separated into components (cells, fat, and skim), and the skim fraction analyzed for total protein, tenascin-C, TGFbeta1, and TGFbeta2. Tenascin-C, TGFbeta1, and TGFbeta2 were detectable in all milk samples. RESULTS: Highest tenascin-C levels on average were found in whole milk, whereas highest mean TGFbeta1 and TGFbeta2 levels were in wean milk. Wean samples on average had higher levels of both TGFbeta1 (26%) and TGFbeta2 (>500%) than matched transitional milk samples. Tenascin-C levels in wean milk were associated with nursing length (p = 0.048). Combining all three milk collection time points, tenascin-C exhibited a weak inverse correlation with TGFbeta1 and TGFbeta2 (p < 0.1). The inverse correlation at the wean time point was stronger for TGFbeta2 than -1 (-0.37 versus -0.25). Tenascin-C, a protein known to promote breast cancer progression, is expressed throughout lactation. CONCLUSION: The inverse correlation with TGFbeta2 in wean milk suggests a possible interaction during breast involution, which should be further investigated. PMID- 26859616 TI - Adsorption of uranyl species on hydroxylated titanium carbide nanosheet: A first principles study. AB - In this work, hydroxylated titanium carbide Ti3C2(OH)2, a representative of the two-dimensional transition metal carbides, has been predicted to be an effective adsorbent for uranyl ions in aqueous environments for the first time using density functional theory simulations. The calculations revealed that the uranyl ion can strongly bind with Ti3C2(OH)2 nanosheet in aqueous solution regardless of the presence of anionic ligands such as OH(-), Cl(-) and NO3(-). The bidentate coordination of uranyl to the surface is energetically more favorable than other adsorption configurations, and the uranyl ion prefers to bind with the deprotonated O adsorption site rather than the protonated one on the hydroxylated surface. During the adsorption process, the chemical adsorption as well as the formation of hydrogen bonds is the dominant factor. PMID- 26859617 TI - Precursors and factors affecting formation of haloacetonitriles and chloropicrin during chlor(am)ination of nitrogenous organic compounds in drinking water. AB - This study investigated the precursors and factors affecting formation of haloacetonitriles (HANs) and chloropicrin (TCNM) during chlorination/chloramination of eight amino acids in the effluent water of V-type clarifying filtration from a drinking water treatment plant. The yields of trichloroacetonitrile (TCAN), dichloroacetonitrile (DCAN) and TCNM were higher during chlorination than during chloramination. Tyrosine and tryptophan produced the greatest amount of DCAN and also generated a small amount of TCAN during chlorination process. Besides, the yields of DCAN were higher than TCNM during chlorination/chloramination. Contact time, Cl2:org-N molar ratios, pH, temperature and bromide ion affected nitrogenous disinfection by-products (N DBPs) formation during chlorination of tryptophan in different degrees. TCAN, DCAN and TCNM formation showed the increasing and then decreasing with prolonged contact time. Higher Cl2:org-N molar ratios improved N-DBPs formation within a certain range. The pH affected N-DBPs formation differently. HANs increased with increasing pH from 5 to 6 and decreased with increasing pH from 6 to 9, while TCNM increased with increasing pH from 5 to 9. Higher temperatures enhanced TCNM formation, but reduced the formation of TCAN and DCAN. The presence of bromide ions improved the yields of HANs and TCNM and shifted N-DBPs to more brominated ones. PMID- 26859618 TI - Toward Intraoperative Detection of Disseminated Tumor Cells in Lymph Nodes with Silicon Nanowire Field Effect Transistors. AB - Within an hour, as little as one disseminated tumor cell (DTC) per lymph node can be quantitatively detected using an intraoperative biosensing platform based on silicon nanowire field-effect transistors (SiNW FET). It is also demonstrated that the integrated biosensing platform is able to detect the presence of circulating tumor cells (CTCs) in the blood of colorectal cancer patients. The presence of DTCs in lymph nodes and CTCs in peripheral blood is highly significant as it is strongly associated with poor patient prognosis. The SiNW FET sensing platform out-performed in both sensitivity and rapidity not only the current standard method based on pathological examination of tissue sections but also the emerging clinical gold standard based on molecular assays. The possibility to achieve accurate and highly sensitive analysis of the presence of DTCs in the lymphatics within the surgery time frame has the potential to spare cancer patients from an unnecessary secondary surgery, leading to reduced patient morbidity, improving their psychological wellbeing and reducing time spent in hospital. This study demonstrates the potential of nanoscale field-effect technology in clinical cancer diagnostics. PMID- 26859620 TI - Effects of Surface Electron Doping and Substrate on the Superconductivity of Epitaxial FeSe Films. AB - Superconductivity in FeSe is greatly enhanced in films grown on SrTiO3 substrates, although the mechanism behind remains unclear. Recently, surface potassium (K) doping has also proven able to enhance the superconductivity of FeSe. Here, by using scanning tunneling microscopy, we compare the K doping dependence of the superconductivity in FeSe films grown on two substrates: SrTiO3 (001) and graphitized SiC (0001). For thick films (20 unit cells (UC)), the optimized superconducting (SC) gaps are of similar size (~9 meV) regardless of the substrate. However, when the thickness is reduced to a few UC, the optimized SC gap is increased up to ~15 meV for films on SrTiO3, whereas it remains unchanged for films on SiC. This clearly indicates that the FeSe/SrTiO3 interface can further enhance the superconductivity, beyond merely doping electrons. Intriguingly, we found that this interface enhancement decays exponentially as the thickness increases, with a decay length of 2.4 UC, which is much shorter than the length scale for relaxation of the lattice strain, pointing to interfacial electron-phonon coupling as the likely origin. PMID- 26859621 TI - Interventions for dysphagia in long-term, progressive muscle disease. AB - BACKGROUND: Normal swallowing function is divided into oral, pharyngeal, and oesophageal phases. The anatomy and physiology of the oral cavity facilitates an oral preparatory phase of swallowing, in which food and liquid are pushed towards the pharynx by the tongue. During pharyngeal and oesophageal phases of swallowing, food and liquid are moved from the pharynx to the stomach via the oesophagus. Our understanding of swallowing function in health and disease has informed our understanding of how muscle weakness can disrupt swallowing in people with muscle disease. As a common complication of long-term, progressive muscle disease, there is a clear need to evaluate the current interventions for managing swallowing difficulties (dysphagia). This is an update of a review first published in 2004. OBJECTIVES: To assess the effects of interventions for dysphagia in people with long-term, progressive muscle disease. SEARCH METHODS: On 11 January 2016, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, AMED, LILACS, and CINAHL. We checked references in the identified trials for additional randomised and quasi-randomised controlled trials. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform on 12 January 2016 for ongoing or completed but unpublished clinical trials. SELECTION CRITERIA: We included randomised and quasi randomised controlled trials that assessed the effect of interventions for managing dysphagia in adults and children with long-term, progressive muscle disease, compared to other interventions, placebo, no intervention, or standard care. Quasi-randomised controlled trials are trials that used a quasi-random method of allocation, such as date of birth, alternation, or case record number. Review authors previously excluded trials involving people with muscle conditions of a known inflammatory or toxic aetiology. In this review update, we decided to include trials of people with sporadic inclusion body myositis (IBM) on the basis that it presents as a long-term, progressive muscle disease with uncertain degenerative and inflammatory aetiology and is typically refractory to treatment. DATA COLLECTION AND ANALYSIS: We applied standard Cochrane methodological procedures. MAIN RESULTS: There were no randomised controlled trials (RCTs) that reported results in terms of the review's primary outcome of interest, weight gain or maintenance. However, we identified one RCT that assessed the effect of intravenous immunoglobulin on swallowing function in people with IBM. The trial authors did not specify the number of study participants who had dysphagia. There was also incomplete reporting of findings from videofluoroscopic investigations, which was one of the review's secondary outcome measures. The study did report reductions in the time taken to swallow, as measured using ultrasound. No serious adverse events occurred during the study, although data for the follow-up period were lacking. It was also unclear whether the non-serious adverse events reported occurred in the treatment group or the placebo group. We assessed this study as having a high risk of bias and uncertain confidence intervals for the review outcomes, which limited the overall quality of the evidence. Using GRADE criteria, we downgraded the quality of the evidence from this RCT to 'low' for efficacy in treating dysphagia, due to limitations in study design and implementation, and indirectness in terms of the population and outcome measures. Similarly, we assessed the quality of the evidence for adverse events as 'low'. From our search for RCTs, we identified two other non-randomised studies, which reported the effects of long-term intravenous immunoglobulin therapy in adults with IBM and lip-strengthening exercises in children with myotonic dystrophy type 1. Headaches affected two participants treated with long-term intravenous immunoglobulin therapy, who received a tailored dose reduction; there were no adverse events associated with lip-strengthening exercises. Both non-randomised studies identified improved outcomes for some participants following the intervention, but neither study specified the number of participants with dysphagia or demonstrated any group-level treatment effect for swallowing function using the outcomes prespecified in this review. AUTHORS' CONCLUSIONS: There is insufficient and low-quality RCT evidence to determine the effect of interventions for dysphagia in long-term, progressive muscle disease. Clinically relevant effects of intravenous immunoglobulin for dysphagia in inclusion body myositis can neither be confirmed or excluded using the evidence presented in this review. Standardised, validated, and reliable outcome measures are needed to assess dysphagia and any possible treatment effect. Clinically meaningful outcomes for dysphagia may require a shift in focus from measures of impairment to disability associated with oral feeding difficulties. PMID- 26859622 TI - On-line enzymatic tailoring of polyketides and peptides in thiotemplate systems. AB - Non-ribosomal peptide synthetases (NRPS) and type I polyketide synthases (PKS) are versatile thiotemplate systems for the programmed assembly of biosynthetic building blocks. Typically, the post-PKS/NRPS enzymes tailor the resulting chains to yield the bioactive natural product scaffolds. However, more and more examples have surfaced showing that important structural modifications take place while the intermediates are still bound to the assembly line. A growing number of enzymatic domains and trans-acting enzymes as well as their recruiting areas in the modules have been identified and characterized. In addition to the widespread on-line alkylations, hydroxylations and heterocyclizations into oxazole/thiazole residues, on-line modifications lead to a variety of ring systems such as cycloethers, lactones, lactams, glutarimides, cyclopropanes, decalins and cyclic biaryls. PMID- 26859625 TI - Fish from Head to Tail: The 9th European Zebrafish Meeting in Oslo. AB - The 9th European Zebrafish Meeting took place recently in Oslo (June 28-July 2, 2015). A total of 650 participants came to hear the latest research news focused on the zebrafish, Danio rerio, and to its distant evolutionary relative medaka, Oryzias latipes. The packed program included keynote and plenary talks, short oral presentations and poster sessions, workshops, and strategic discussions. The meeting was a great success and revealed dramatically how important the zebrafish in particular has become as a model system for topics, such as developmental biology, functional genomics, biomedicine, toxicology, and drug development. A new emphasis was given to its potential as a model for aquaculture, a topic of great economic interest to the host country Norway and for the future global food supply in general. Zebrafish husbandry as well as its use in teaching were also covered in separate workshops. As has become a tradition in these meetings, there was a well-attended Wellcome Trust Sanger Institute and ZFIN workshop focused on Zebrafish Genome Resources on the first day. The full EZM 2015 program with abstracts can be read and downloaded from the EZM 2015 Web site zebrafish2015.org . PMID- 26859626 TI - Phase Behavior of Poly(vinylidene fluoride)-graft-poly(diethylene glycol methyl ether methacrylate) in Alcohol-Water System: Coexistence of LCST and UCST. AB - A thermoresponsive polymer poly(diethylene glycol methyl ether methacrylate) (PMeO2MA) is grafted from poly(vinylidene fluoride) (PVDF) backbone by using a combined ATRC and ATRP technique with a high conversion (69%) of the monomer to produce the graft copolymer (PD). It is highly soluble polymer and its solution property is studied by varying polarity in pure solvents (water, methanol, isopropanol) and also in mixed solvents (water-methanol and water-isopropanol) by measuring the hydrodynamic size (Z-average) of the particles by dynamic light scattering (DLS). The variation of Z-average size with temperature of the PD solution (0.2%, w/v) indicates a lower critical solution temperature (LCST)-type phase transition (T(PL)) in aqueous medium, an upper critical solution temperature (UCST)-type phase transition (T(PU)) in isopropanol medium, and no such phase transition for methanol solution. In the mixed solvent (water + isopropanol) at 0-20% (v/v) isopropanol the TPL increases, whereas the T(PU) decreases at 92-100% with isopropanol content. For the mixture 20-90% isopropanol, PD particles having larger sizes (400-750 nm) exhibit neither any break in Z-average size-temperature plot nor any cloudiness, indicating their dispersed swelled state in the medium. In the methanol + water mixture with methanol content of 0-30%, T(PL) increases, and at 40-60% both UCST- and LCST type phase separations occur simultaneously, but at 70-90% methanol the swelled state of the particles (size 250-375 nm) is noticed. For 50 vol % methanol by varying polymer concentration (0.07-0.2% w/v) we have drawn a quasibinary phase diagram that indicates an approximate inverted hourglass phase diagram where a swelled state exists between two single phase boundary produced from LCST- and UCST-type phase transitions. An attempt is made to understand the phase separation process by temperature-dependent (1)H NMR spectroscopy along with transmission electron microscopy. PMID- 26859619 TI - Aqueous Glycosylation of Unprotected Sucrose Employing Glycosyl Fluorides in the Presence of Calcium Ion and Trimethylamine. AB - We report a synthetic glycosylation reaction between sucrosyl acceptors and glycosyl fluoride donors to yield the derived trisaccharides. This reaction proceeds at room temperature in an aqueous solvent mixture. Calcium salts and a tertiary amine base promote the reaction with high site-selectivity for either the 3'-position or 1'-position of the fructofuranoside unit. Because nonenzymatic aqueous oligosaccharide syntheses are underdeveloped, mechanistic studies were carried out in order to identify the origin of the selectivity, which we hypothesized was related to the structure of the hydroxyl group array in sucrose. The solution conformation of various monodeoxysucrose analogs revealed the co operative nature of the hydroxyl groups in mediating both this aqueous glycosyl bond-forming reaction and the site-selectivity at the same time. PMID- 26859628 TI - Real-Time TaqMan PCR Assay for the Detection of Heat-Labile and Heat-Stable Enterotoxin Genes in a Geographically Diverse Collection of Enterotoxigenic Escherichia coli Strains and Stool Specimens. AB - Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhea in children under the age of 5 years in developing countries and are the leading bacterial agent of traveler's diarrhea in persons traveling to these countries. ETEC strains secrete heat-labile (LT) and/or heat-stable (ST) enterotoxins that induce diarrhea by causing water and electrolyte imbalance. We describe the validation of a real-time TaqMan PCR (RT-PCR) assay to detect LT, ST1a, and ST1b enterotoxin genes in E. coli strains and in stool specimens. We validated LT/ST1b duplex and ST1a single-plex RT-PCR assay using a conventional PCR assay as a gold standard with 188 ETEC strains and 42 non-ETEC strains. We validated LT/ST1b duplex and ST1a single-plex RT-PCR assay in stool specimens (n = 106) using traditional culture as the gold standard. RT- PCR assay sensitivities for LT, ST1a, and ST1b detection in strains were 100%, 100%, and 98%; specificities were 95%, 98%, and 99%, and Pearson correlation coefficient r was 0.9954 between RT PCR assay and the gold standard. In stool specimens, RT-PCR assay sensitivities for LT, ST1a, and ST1b detection were 97%, 100%, and 97%; and specificities were 99%, 94%, and 97%. Pearson correlation coefficient r was 0.9975 between RT-PCR results in stool specimens and the gold standard. Limits of detection of LT, ST1a, and ST1b by RT-PCR assay were 0.1 to1.0 pg/MUL and by conventional PCR assay were 100 to1000 pg/MUL. The accuracy, rapidity and sensitivity of this RT PCR assay is promising for ETEC detection in public health/clinical laboratories and for laboratories in need of an independent method to confirm results of other culture independent diagnostic tests. PMID- 26859629 TI - Monitoring Inhaler Inhalations Using an Acoustic Sensor Proximal to Inhaler Devices. AB - BACKGROUND: The efficacy of drug delivery from inhalers is very much dependent on the user's peak inspiratory flow rate (PIFR). Current methods to measure PIFR in inhalers are based on subjective checklists. There is a lack of methods currently available to objectively remotely monitor PIFR in pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs). In this study, for the first time, non-contact acoustic methods were employed to estimate PIFR through three commonly used inhalers (DiskusTM DPI, TurbuhalerTM DPI, and EvohalerTM pMDI) with the aim of applying these methods to remotely monitor inhaler inhalation technique in future clinical applications. METHODS: Each inhaler was placed inside an airtight container connected to a spirometer to measure PIFR. A high quality microphone was placed 5 cm from the mouthpiece of the inhalers to record inhalation sounds. Over 2000 inhaler inhalation sounds were recorded from 11 healthy participants. A range of temporal and spectral acoustic features from the inhalation sounds were correlated with PIFR. The variation of acoustic features and the repeatability of the inhalation acoustic spectral profile were investigated to further characterize inhaler inhalation sounds and to determine the reliability of acoustics to estimate PIFR. RESULTS: All acoustic features were significantly correlated with PIFR (p < 0.001). The mean power of the inhalation sound generated the most consistent correlation across all inhalers [R2 = 0.77 (DiskusTM), R2 = 0.7 (TurbuhalerTM), R2 = 0.75 (EvohalerTM)]. Acoustic features generated low variation and the spectral profile of inhalation sounds was repeatable regardless of flow rate, suggesting that acoustic methods are a reliable method of estimating PIFR. CONCLUSIONS: The methods presented in this study may be employed in a wearable monitoring device in future applications to measure inhaler PIFR. Objective monitoring of PIFR in inhalers may help patients improve their inhaler inhalation technique and therefore may be of significant clinical benefit to both patients and clinicians. PMID- 26859632 TI - A 5-year-old Girl with Chest Wall Mass. PMID- 26859633 TI - Orthopedic Complications in Former Bacillus Calmette-Guerin Osteitis Patients. AB - In 160 Finnish former Bacillus Calmette-Guerin osteitis patients, a questionnaire revealed that later in life, 22 (13.8%) had mild orthopedic complications as a consequence of the infection. PMID- 26859631 TI - Prenatal Arsenic Exposure and Birth Outcomes among a Population Residing near a Mining-Related Superfund Site. AB - BACKGROUND: Limited epidemiologic data exist on prenatal arsenic exposure and fetal growth, particularly in the context of co-exposure to other toxic metals. OBJECTIVE: We examined whether prenatal arsenic exposure predicts birth outcomes among a rural U.S. population, while adjusting for exposure to lead and manganese. METHODS: We collected maternal and umbilical cord blood samples at delivery from 622 mother-infant pairs residing near a mining-related Superfund site in Northeast Oklahoma. Whole blood arsenic, lead, and manganese were measured using inductively coupled plasma mass spectrometry. We modeled associations between arsenic concentrations and birth weight, gestational age, head circumference, and birth weight for gestational age. RESULTS: Median (25th 75th percentile) maternal and umbilical cord blood metal concentrations, respectively, were as follows: arsenic, 1.4 (1.0-2.3) and 2.4 (1.8-3.3) MUg/L; lead, 0.6 (0.4-0.9) and 0.4 (0.3-0.6) MUg/dL; manganese, 22.7 (18.8-29.3) and 41.7 (32.2-50.4) MUg/L. We estimated negative associations between maternal blood arsenic concentrations and birth outcomes. In multivariable regression models adjusted for lead and manganese, an interquartile range increase in maternal blood arsenic was associated with -77.5 g (95% CI: -127.8, -27.3) birth weight, 0.13 weeks (95% CI: -0.27, 0.01) gestation, -0.22 cm (95% CI: -0.42, -0.03) head circumference, and -0.14 (95% CI: -0.24, -0.04) birth weight for gestational age z-score units. Interactions between arsenic concentrations and lead or manganese were not statistically significant. CONCLUSIONS: In a population with environmental exposure levels similar to the U.S. general population, maternal blood arsenic was negatively associated with fetal growth. Given the potential for relatively common fetal and early childhood arsenic exposures, our finding that prenatal arsenic can adversely affect birth outcomes is of considerable public health importance. CITATION: Claus Henn B, Ettinger AS, Hopkins MR, Jim R, Amarasiriwardena C, Christiani DC, Coull BA, Bellinger DC, Wright RO. 2016. Prenatal arsenic exposure and birth outcomes among a population residing near a mining-related Superfund site. Environ Health Perspect 124:1308-1315; http://dx.doi.org/10.1289/ehp.1510070. PMID- 26859630 TI - Disruptive Mood Dysregulation Disorder and Bipolar Disorder Not Otherwise Specified: Fraternal or Identical Twins? AB - OBJECTIVE: The purpose of this study was to examine similarities and differences between disruptive mood dysregulation disorder (DMDD) and bipolar disorder not otherwise specified (BP-NOS) in baseline sociodemographic and clinical characteristics and 36 month course of irritability in children 6-12.9 years of age. METHODS: A total of 140 children with DMDD and 77 children with BP-NOS from the Longitudinal Assessment of Manic Symptoms cohort were assessed at baseline, then reassessed every 6 months for 36 months. RESULTS: Groups were similar on most sociodemographic and baseline clinical variables other than most unfiltered (i.e., interviewer-rated regardless of occurrence during a mood episode) Young Mania Rating Scale (YMRS) and parent-reported General Behavior Inventory-10 Item Mania (PGBI-10M) items. Children with DMDD received lower scores on every item (including irritability) except impaired insight; differences were significant except for sexual interest and disruptive-aggressive behavior. Children with DMDD received lower scores on eight of 10 PGBI-10M items, the other two items rated irritability. Youth with DMDD were significantly less likely to have a biological parent with a bipolar diagnosis than were youth with BP-NOS. Children with DMDD were more likely to be male and older than children with BP-NOS, both small effect sizes, but had nearly double the rate of disruptive behavior disorders (large effect). Caregiver ratings of irritability based on the Child and Adolescent Symptom Inventory-4R (CASI-4R) were comparable at baseline; the DMDD group had a small but significantly steeper decline in scores over 36 months relative to the BP-NOS group (b = -0.24, SE = 0.12, 95% CI -0.48 to -0.0004). Trajectories for both groups were fairly stable, in the midrange of possible scores. CONCLUSIONS: In a sample selected for elevated symptoms of mania, twice as many children were diagnosed with DMDD than with BP-NOS. Children with DMDD and BP-NOS are similar on most characteristics other than manic symptoms, per se, and parental history of bipolar disorder. Chronic irritability is common in both groups. Comprehensive evaluations are needed to diagnose appropriately. Clinicians should not assume that chronic irritability leads exclusively to a DMDD diagnosis. PMID- 26859634 TI - Enterovirus-D68 in the Cerebrospinal Fluid of Two Children with Aseptic Meningitis. AB - This case report describes two previously healthy children with aseptic meningitis whose cerebrospinal fluid was positive for enterovirus-D68, which indicates direct involvement of this infectious agent in the development of this neurologic disease. PMID- 26859635 TI - On-Line Hemodiafiltration: All That Glitters Is Not Gold. PMID- 26859636 TI - Vertical Ridge Augmentation With Mandibular Lingual Torus Block Graft. PMID- 26859638 TI - Corrigendum: Photo-generated metamaterials induce modulation of CW terahertz quantum cascade lasers. PMID- 26859637 TI - Tenofovir and bone health. AB - PURPOSE OF REVIEW: With continued improvements to the antiviral efficacy and tolerability of antiretroviral therapy, long-term safety of antiretroviral therapy has become paramount. Low bone mineral density and fragility fractures are more common in HIV-infected individuals than in the general population. The aims of this review are to describe potential mechanisms underlying the adverse effects of tenofovir on bone, clinical studies of tenofovir disoproxil fumarate (TDF) and bone, and more recent bone data on tenofovir alafenamide. RECENT FINDING: Several studies have demonstrated an approximately 1-3% greater bone mineral density loss with TDF compared with other agents. Recent studies with tenofovir alafenamide have shown improved bone (and renal) safety with similar virologic efficacy when compared to TDF. SUMMARY: Given these findings, TDF containing regimens may be gradually replaced with non-TDF containing regimens for the treatment of HIV infection, especially in those at higher risk for fragility fracture. PMID- 26859639 TI - Caring in Correctional Nursing: A Systematic Search and Narrative Synthesis. AB - Registered nurses are the primary healthcare providers for offenders in correctional facilities. The way in which correctional nurses care for offenders can be difficult in this context. Following a systematic review and narrative synthesis of literature regarding how correctional nurses show caring for offenders three themes emerged: the struggle of custody and caring (conflicting ethical and philosophical ideologies, correctional priorities that override nursing priorities, safety and security), the need to be nonjudgmental (judgmental attitudes can impact care; focus on health not the crime), and the importance of boundaries. Implications for practice focus on recommendations to promote caring in correctional nursing; the outcome of which will potentially enhance quality of care for offenders and improve working environments for nurses. PMID- 26859640 TI - Pediatric Sexual Abuse Disclosures: The "Other" Category. PMID- 26859641 TI - Challenging the Myths: The Way Forward in Prevention of Rapes. PMID- 26859642 TI - Women in Transition to Health: A Theory-Based Intervention to Increase Engagement in Care for Women Recently Released From Jail or Prison. AB - The time after incarceration is widely regarded as tenuous and stressful, and for women living with chronic illness, self-management is yet another stressor. Intervening before the individual is overwhelmed is critical to ensuring success. In this article the Women in Transition to Health, a nurse-led intervention based on Lazarus and Folkman's Transactional Model of Stress and Coping, designed to improve health outcomes in women recently released from jail or prison is described. Motivational interviewing and case management are used to strengthen coping skills and encourage engagement in care. Using the stress model to address the unique needs of this population holds promise for improving health and quality of life. PMID- 26859643 TI - Effect of Repetitive Sub-concussive Head Impacts on Ocular Near Point of Convergence. AB - This study intended to examine effects of repetitive sub-concussive head impacts on ocular near point of convergence (NPC). 20 healthy young adult soccer players were assigned to either a heading or control group. Heading subjects completed 10 headers of soccer balls projected at a speed of 11.2 m/s. Control subjects did not perform heading. Linear head acceleration was measured with a triaxial accelerometer. The NPC assessment was performed at pre-, 0 h post-, and 24 h post heading. During the NPC assessment participants were seated and a visual target was moved towards the eyes at 1cm/sec. The participant signaled when he/she experienced diplopia or deviation of the eye was observed, and the distance was recorded. The assessment was repeated twice and average NPC scores were used for further analysis. Soccer heading induced mean group head accelerations of 14.49+/ 5.4 g. Mild head impacts led to an increased NPC distance, which was supported by a significant Group x Time interaction. In the heading group, 0 h post- and 24 h post-heading NPC scores were significantly receded compared to baseline. Conversely, NPC scores for the control group showed no difference over time. Our findings indicate that mild frontal head impacts affekt NPC for a minimum of 24 h post heading, suggesting that oculomotor processes are disrupted, at least transiently, by repetitive mild head impact. PMID- 26859644 TI - Effects of Wearing Compression Stockings on the Physical Performance of T2DM Men with MetS. AB - Metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM) are associated with macro- and microcirculatory complications that reduce physical performance. Wearing compression garments to potentially optimize hemodynamics has been discussed. This study investigates the effects of wearing compression stockings on physical performance-related variables in type 2 diabetic men with metabolic syndrome (n=9, 57+/-12 years, BMI: 36+/-4 kg/m(2)). Participants served as their own controls in a randomized 3*3 crossover study wearing below-knee stockings with either compression (24 or 30 mmHg ankle pressure) or no compression. Venous pooling and lower limb oxygenation profiles were determined with near-infrared spectroscopy and arterial oxygen saturation was determined using a pulse oxymeter. Measurements were performed in the supine lying position, during standing, following 10 tiptoe exercises and after submaximal intensity cycling. In addition, lactate and erythrocyte deformability were analyzed in capillary blood pre- and post-exercise. Erythrocyte deformability was analyzed using a laser-assisted optical rotational red cell analyzer. No significant differences in any variables when wearing different compression or regular stockings were evident at any point of measurement. This study did not reveal any beneficial effects of wearing compression stockings at rest and during acute bouts of moderately intense exercise in this particular patient group. PMID- 26859645 TI - Application of a Sub-set of Skinfold Sites for Ultrasound Measurement of Subcutaneous Adiposity and Percentage Body Fat Estimation in Athletes. AB - Body composition assessment is an integral feature of elite sport as optimization facilitates successful performance. This study aims to refine the use of B-mode ultrasound in the assessment of athlete body composition by determining suitable sites for measurement. 67 elite athletes recruited from the Human Performance Laboratory, University College Cork, Ireland, underwent dual measurement of body composition. Subcutaneous adipose tissue thickness at 7 anatomical sites were measured using ultrasound and compared to percentage body fat values determined using Dual-Energy X-ray Absorptiometry. Multiple linear regressions were performed and an equation to predict percentage body fat was derived. The present study found subcutaneous adipose tissue depths at the triceps, biceps, anterior thigh and supraspinale sites correlated significantly with percentage body fat by X-ray absorptiometry (all p<0.05). Summation of the depths at these locations correlated strongly with percentage body fat by Dual-Energy X-ray Absorptiometry (R2=0.879). The triceps, biceps, anterior thigh and supraspinale sites are suitable anatomical landmarks for the estimation of %BF using B-mode ultrasound. Use of B-mode ultrasound in the assessment of athlete body composition confers many benefits including lack of ionising radiation and its potential to be used as a portable field tool. PMID- 26859647 TI - Modified Nasal Trumpet for Airway Management. PMID- 26859646 TI - Quaternary Lidocaine Derivative QX-314 Activates and Permeates Human TRPV1 and TRPA1 to Produce Inhibition of Sodium Channels and Cytotoxicity. AB - BACKGROUND: The relatively membrane-impermeable lidocaine derivative QX-314 has been reported to permeate the ion channels transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential cation channel, subfamily A, member 1 (TRPA1) to induce a selective inhibition of sensory neurons. This approach is effective in rodents, but it also seems to be associated with neurotoxicity. The authors examined whether the human isoforms of TRPV1 and TRPA1 allow intracellular entry of QX-314 to mediate sodium channel inhibition and cytotoxicity. METHODS: Human embryonic kidney 293 (HEK-293) cells expressing wild type or mutant human (h) TRPV1 or TRPA1 constructs as well as the sodium channel Nav1.7 were investigated by means of patch clamp and ratiometric calcium imaging. Cytotoxicity was examined by flow cytometry. RESULTS: Activation of hTRPA1 by carvacrol and hTRPV1 by capsaicin produced a QX-314-independent reduction of sodium current amplitudes. However, permeation of QX-314 through hTRPV1 or hTRPA1 was evident by a concentration-dependent, use-dependent inhibition of Nav1.7 activated at 10 Hz. Five and 30 mM QX-314 activated hTRPV1 via mechanisms involving the intracellular vanilloid-binding domain and hTRPA1 via unknown mechanisms independent of intracellular cysteins. Expression of hTRPV1, but not hTRPA1, was associated with a QX-314-induced cytotoxicity (viable cells 48 +/- 5% after 30 mM QX-314) that was ameliorated by the TRPV1 antagonist 4-(3-chloro-2 pyridinyl)-N-[4-(1,1-dimethylethyl)phenyl]-1-piperazinecarboxamide (viable cells 81 +/- 5%). CONCLUSIONS: The study data demonstrate that QX-314 directly activates and permeates the human isoforms of TRPV1 and TRPA1 to induce inhibition of sodium channels, but also a TRPV1-dependent cytotoxicity. These results warrant further validation of this approach in more intact preparations and may be valuable for the development of this concept into clinical practice. PMID- 26859648 TI - Comparative Evaluation of Efficacy and Tolerability of Glycolic Acid, Salicylic Mandelic Acid, and Phytic Acid Combination Peels in Melasma. AB - BACKGROUND: Melasma is acquired symmetric hypermelanosis characterized by light to-deep brown pigmentation over cheeks, forehead, upper lip, and nose. Treatment of this condition is difficult and associated with high recurrence rates. Chemical peels have become a popular modality in the treatment of melasma. OBJECTIVE: To compare the therapeutic efficacy and tolerability of glycolic acid (35%) versus salicylic-mandelic (SM) acid (20% salicylic/10% mandelic acid) versus phytic combination peels in Indian patients with melasma. MATERIALS AND METHODS: Ninety patients diagnosed with melasma were randomly assigned into 3 groups of 30 patients each. Group A received glycolic acid (GA-35%) peel, Group B received SM acid, and Group C received phytic combination peels. Each group was primed with 4% hydroquinone and 0.05% tretinoin cream for 4 weeks before treatment. Chemical peeling was done after every 14 days in all groups until 12 weeks. Clinical evaluation using melasma area and severity index (MASI) score and photography was recorded at every visit and follow-up was done until 20 weeks. RESULTS: There was a decrease in MASI score in all 3 groups but it was statistically significantly lower in Group A than Group C (p = .00), and it was also statistically significantly lower in Group B than Group C (p = .00) but there was no statistically significant difference between Groups A and B (p = .876). Objective response to treatment evaluated by reduction in MASI scoring after 12 weeks was 62.36% reduction in GA group, 60.98% reduction in SM group, and 44.71% in phytic acid group. CONCLUSION: It is concluded that GA (35%) and SM acid peels are both equally efficacious and a safe treatment modality for melasma in Indian skin, and are more effective than phytic acid peels. Salicylic-mandelic peels are better tolerated and more suitable for Indian skin. PMID- 26859649 TI - Purse-String Anchor. PMID- 26859650 TI - Successful Treatment of Argyria Using the Picosecond Alexandrite Laser. PMID- 26859651 TI - The Use of Poly-L-Lactic Acid in the Gluteal Area. PMID- 26859652 TI - "Boomerang Technique: " Simple Excision With Periosteal Suspension for Correction of Mild-to-Moderate Cicatricial Ectropion. PMID- 26859653 TI - The Bilateral Dufourmentel Flap for Repair of Nasal Dorsum Defects After Mohs Micrographic Surgery. AB - BACKGROUND: Single-stage repairs of large nasal dorsum defects risk introducing lower nasal distortion. OBJECTIVE: To describe the authors experience with the "birhombic" flap, a bilateral Dufourmentel rhomboid flap, for repair of nasal surgical defects after Mohs micrographic surgery. MATERIALS AND METHODS: The authors performed a retrospective chart review of patients who underwent birhombic flap repair of the nose by a single physician after Mohs micrographic surgery from 2008 to 2013 at the Medical University of South Carolina. RESULTS: Thirty-eight patients were identified on whom the birhombic flap repair was performed on the nasal dorsum over a 6-year period. There were no significant complications. Alar position remained neutral and nasal profile remained unaltered in all cases. Postoperatively, pulsed dye laser was performed in 8 patients (21%) and dermabrasion in 11 patients (29%). All patients achieved very good or excellent final aesthetic results. CONCLUSION: The birhombic flap is a reproducible, one-stage flap for small to large defects of the nasal dorsum that consistently produces topographic restoration with minimal risk of aesthetic or functional complication. The use of 2 opposing flaps redistributes the secondary defect, thus minimizing the potential for lower nasal distortion when closing the flaps' donor sites. PMID- 26859654 TI - Safety of Prefilled Buffered Lidocaine Syringes With and Without Epinephrine. AB - BACKGROUND: Lidocaine is often used in conjunction with epinephrine and sodium bicarbonate for local anesthesia. Compounding lidocaine as needed can be highly disruptive to clinic flow, which has led many dermatology clinics to prefill syringes with these solutions, but current regulations recommend the disposal of these preparations within 12 hours, creating medical waste. OBJECTIVE: To evaluate the safety of buffered lidocaine with and without epinephrine drawn from multiuse vials and stored for up to 4 weeks. METHODS: Syringes were filled with lidocaine 1%, lidocaine 1% with 1:100,000 epinephrine, lidocaine 1% with bicarbonate (10:1 ratio), or lidocaine 1% with 1:100,000 epinephrine with bicarbonate (10:1 ratio). The samples were stored for 4 weeks either at controlled room or controlled cold temperature. They were then centrifuged and cultured for anaerobic bacteria, aerobic bacteria, and fungus. RESULTS: Prefilled lidocaine syringes are not subject to bacterial or fungal growth after being stored for 4 weeks. CONCLUSION: Prefilled syringes of lidocaine remain safe to use for up to 4 weeks, and the current regulations placed on the disposal of these solutions should be revisited. PMID- 26859655 TI - Beyond the Protein-Coding Sequence: Noncoding RNAs in the Pathogenesis of Type 2 Diabetes. AB - Diabetes mellitus results from a deficiency or failure to maintain normal glucose homeostasis. The most common form of the disease is type 2 diabetes (T2D), a progressive metabolic disorder characterized by elevated glucose levels that develops in response to either multi-organ insulin resistance or insufficient insulin secretion from pancreatic beta-cells. Although the etiology of T2D is complex, many factors are known to contribute to defects of glucose homeostasis, including obesity, unhealthy lifestyle choices, genetic susceptibility, and environmental exposures. In addition to these factors, noncoding RNAs (ncRNAs) have been recently implicated in the pathogenesis of T2D, playing roles in several of the pathophysiological mechanisms underlying the disease, particularly in insulin-sensitive tissues such as pancreatic beta-cells, liver, muscle, and adipose tissue. A growing number of publications demonstrate that polymorphisms in ncRNAs or their target genes may represent a new class of genetic variation contributing to the development of T2D. This review summarizes both the current state of knowledge of ncRNAs, specifically microRNAs (miRNAs), involved in the regulation of beta-cell function, insulin sensitivity, and insulin action in peripheral organs. The role of genetic variation in miRNAs or miRNA binding sites in the pathogenesis of T2D is also discussed. While far less is known about the impact of long ncRNAs (lncRNAs) in the development of T2D, emerging evidence suggests that these molecules may be able to contribute to beta-cell dysfunction in response to hyperglycemia. This article provides an overview of the studies conducted to date in this field, focusing on lncRNAs that are dysregulated in human pancreatic islets. PMID- 26859656 TI - Novel Genetic Actors of Diabetes-Associated Microvascular Complications: Retinopathy, Kidney Disease and Neuropathy. AB - Both type 1 and type 2 diabetes mellitus can lead to the common microvascular complications of diabetic retinopathy, kidney disease, and neuropathy. Diabetic patients do not universally develop these complications. Long duration of diabetes and poor glycemic control explain a lot of the variability in the development of microvascular complications, but not all. Genetic factors account for some of the remaining variability because of the heritability and familial clustering of these complications. There have been a large number of investigations, including linkage studies, candidate gene studies, and genome wide association studies, all of which have sought to identify the specific variants that increase susceptibility. For retinopathy, several genome-wide association studies have been performed in small or midsize samples, but no reproducible loci across the studies have been identified. For diabetic kidney disease, genome-wide association studies in larger samples have been performed, and loci for this complication are beginning to emerge. However, validation of the existing discoveries, and further novel discoveries in larger samples is ongoing. The amount of genetic research into diabetic neuropathy has been very limited, and much is dedicated to the understanding of genetic risk factors only. Collaborations that pool samples and aim to detect phenotype classifications more precisely are promising avenues for a better explanation of the genetics of diabetic microvascular complications. PMID- 26859658 TI - Metformin Treatment Does Not Affect Testicular Size in Offspring Born to Mothers with Gestational Diabetes. AB - OBJECTIVES: Studies in rodents suggest that metformin treatment during pregnancy may have harmful effects on testicular development in offspring. Our aim was to determine whether metformin treatment of gestational diabetes mellitus (GDM) affects testicular size in male offspring. METHODS: We compared the testicular size in prepubertal boys born to mothers who participated in a randomized controlled trial (RCT) comparing metformin with insulin in the treatment of GDM. Twenty-five (42.4% of invited) and 27 (52.9% of invited) boys whose mothers had been treated with metformin or insulin, respectively, participated in the study. Testicular size was measured by a ruler, an orchidometer, and by ultrasonography at the age of 33 to 85 months. RESULTS: The mean age of the boys was 60 months at the time of examination, and did not differ between the metformin and insulin group (p = 0.88). There was no difference in testicular size between the boys in the two groups (p always >= 0.40), and there were no significant differences in height, weight, BMI, BMI z-score, or waist-to-hip ratio (WHR) between the boys in the groups. CONCLUSIONS: Prepubertal testicular size did not differ between offspring born to metformin-treated mothers and those born to insulin-treated mothers. PMID- 26859659 TI - Genvoya--a new 4-drug combination for HIV. PMID- 26859660 TI - Selexipag (Uptravi) for pulmonary arterial hypertension. PMID- 26859661 TI - Patiromer (Veltassa) for hyperkalemia. PMID- 26859657 TI - Genetic Determination of Serum Levels of Diabetes-Associated Adipokines. AB - Adipose tissue secretes an abundance of proteins. Some of these proteins are known as adipokines and adipose-derived hormones which have been linked with metabolic disorders, including type 2 diabetes, and even with cancer. Variance in serum adipokine concentration is often closely associated with an increase (obesity) or decrease (lipodystrophy) in fat tissue mass, and it is affected by age, gender, and localization of the adipose tissue. However, there may be genetic variants which, in consequence, influence the serum concentration of a certain adipokine, and thereby promote metabolic disturbances or, with regard to the "protective" allele, exert beneficial effects. This review focuses on the genetic determination of serum levels of the following adipokines: adiponectin, chemerin, leptin, progranulin, resistin, retinol binding protein 4, vaspin, adipsin, apelin, and omentin. The article reports on the latest findings from genome-wide association studies (GWAS) and candidate gene studies, showing variants located in/nearby the adipokine genes and other (non-receptor) genes. An extra chapter highlights adipokine-receptor variants. Epigenetic studies on adipokines are also addressed. PMID- 26859662 TI - The Case for Reforming Drug Naming: Should Brand Name Trademark Protections Expire upon Generic Entry? PMID- 26859663 TI - The Use of Delta Neutrophil Index and Myeloperoxidase Index for Predicting Acute Complicated Appendicitis in Children. AB - BACKGROUND: In children with acute appendicitis, 30% to 75% present with a complication, such as perforation, and the early diagnosis of complications is known to improve outcomes. Serum delta neutrophil index (DNI) and myeloperoxidase index (MPXI) are new inflammatory markers, and thus, in the present study, the authors evaluated the predictive values of these two markers for the presence of a complication in children with acute appendicitis. METHODS: This retrospective observational study was conducted on 105 consecutive children (<12 years old) with acute appendicitis treated over a 31-month period. DNI, MPXI, C-reactive protein (CRP), and white blood cells (WBCs) were measured in an emergency department and investigated with respect to their abilities to predict the presence of acute complicated appendicitis. RESULTS: Twenty-nine of the 105 patients (median age, 9 years) were allocated to the complicated group (27.6%) and 76 to the non-complicated group (72.4%). Median serum DNI and CRP were significantly higher in the complicated group [0% vs. 2.2%, p<0.001 and 0.65 mg/dL vs. 8.0 mg/dL, p<0.001], but median MPXI was not (p = 0.316). Area under curve (AUC) for the ability of serum DNI and CRP to predict the presence of acute complicated appendicitis were 0.738 and 0.840, respectively. Multiple logistic regression analyses showed initial CRP [odds ratio 1.301, 95% confidence interval (1.092-1.549), p = 0.003] significantly predicted the presence of a complication. The optimal cutoff for serum CRP was 4.0 mg/dL (sensitivity 69%, specificity 83%, AUC 0.840). CONCLUSIONS: Although serum DNI values were significantly higher in children with acute complicated appendicitis, no evidence was obtained to support the notion that serum DNI or serum MPXI aid the differentiation of acute complicated and non-complicated appendicitis in the ED setting. PMID- 26859664 TI - Simple Scoring System and Artificial Neural Network for Knee Osteoarthritis Risk Prediction: A Cross-Sectional Study. AB - BACKGROUND: Knee osteoarthritis (OA) is the most common joint disease of adults worldwide. Since the treatments for advanced radiographic knee OA are limited, clinicians face a significant challenge of identifying patients who are at high risk of OA in a timely and appropriate way. Therefore, we developed a simple self assessment scoring system and an improved artificial neural network (ANN) model for knee OA. METHODS: The Fifth Korea National Health and Nutrition Examination Surveys (KNHANES V-1) data were used to develop a scoring system and ANN for radiographic knee OA. A logistic regression analysis was used to determine the predictors of the scoring system. The ANN was constructed using 1777 participants and validated internally on 888 participants in the KNHANES V-1. The predictors of the scoring system were selected as the inputs of the ANN. External validation was performed using 4731 participants in the Osteoarthritis Initiative (OAI). Area under the curve (AUC) of the receiver operating characteristic was calculated to compare the prediction models. RESULTS: The scoring system and ANN were built using the independent predictors including sex, age, body mass index, educational status, hypertension, moderate physical activity, and knee pain. In the internal validation, both scoring system and ANN predicted radiographic knee OA (AUC 0.73 versus 0.81, p<0.001) and symptomatic knee OA (AUC 0.88 versus 0.94, p<0.001) with good discriminative ability. In the external validation, both scoring system and ANN showed lower discriminative ability in predicting radiographic knee OA (AUC 0.62 versus 0.67, p<0.001) and symptomatic knee OA (AUC 0.70 versus 0.76, p<0.001). CONCLUSIONS: The self-assessment scoring system may be useful for identifying the adults at high risk for knee OA. The performance of the scoring system is improved significantly by the ANN. We provided an ANN calculator to simply predict the knee OA risk. PMID- 26859665 TI - Measurement Variability of Persistent Pulmonary Subsolid Nodules on Same-Day Repeat CT: What Is the Threshold to Determine True Nodule Growth during Follow Up? AB - PURPOSE: To assess the measurement variability of subsolid nodules (SSNs) in follow-up situations and to compare the degree of variability between measurement metrics. METHODS: Two same-day repeat-CT scans of 69 patients (24 men and 45 women) with 69 SSNs were randomly assigned as initial or follow-up scans and were read by the same (situation 1) or different readers (situation 2). SSN size and solid portion size were measured in both situations. Measurement variability was calculated and coefficients of variation were used for comparisons. RESULTS: Measurement variability for the longest and average diameter of SSNs was +/-1.3 mm (+/-13.0%) and +/-1.3 mm (+/-14.4%) in situation 1, and +/-2.2 mm (+/-21.0%) and +/-2.1 mm (+/-21.3%) in situation 2, respectively. For solid portion, measurement variability on lung and mediastinal windows was +/-1.2 mm (+/-27.1%) and +/-0.8 mm (+/-24.0%) in situation 1, and +/-3.7 mm (+/-61.0%) and +/-1.5 mm (+/-47.3%) in situation 2, respectively. There were no significant differences in the degree of variability between the longest and average diameters and between the lung and mediastinal window settings (p>0.05). However, measurement variability significantly increased when the follow-up and initial CT readers were different (p<0.001). CONCLUSIONS: A cutoff of +/-2.2 mm can be reliably used to determine true nodule growth on follow-up CT. Solid portion measurements were not reliable in evaluating SSNs' change when readers of initial and follow-up CT were different. PMID- 26859668 TI - Lung cancer in HIV-infected patients and the role of targeted therapy. AB - Lung cancer is one of the most common malignancies in HIV-infected patients. Prevalence and mortality outcomes are higher in HIV-infected populations than in noninfected patients. There are several oral agents available for patients who harbor specific mutations, but little is known about mutations and affected pathways in HIV-infected patients with lung cancer. Recent trials have facilitated the inclusion of HIV-infected patients in clinical trials, but the population is remains underrepresented in oncology trials. Here, we review the literature on lung cancer in HIV-infected patients, and discuss common mutations in lung cancer and HIV-infected patients, the role of mutational analysis, and the potential role of targeted therapy in the treatment of lung cancer in HIV infected populations. PMID- 26859666 TI - Identification of Novel Immunogenic Proteins of Neisseria gonorrhoeae by Phage Display. AB - Neisseria gonorrhoeae is one of the most prevalent sexually transmitted diseases worldwide with more than 100 million new infections per year. A lack of intense research over the last decades and increasing resistances to the recommended antibiotics call for a better understanding of gonococcal infection, fast diagnostics and therapeutic measures against N. gonorrhoeae. Therefore, the aim of this work was to identify novel immunogenic proteins as a first step to advance those unresolved problems. For the identification of immunogenic proteins, pHORF oligopeptide phage display libraries of the entire N. gonorrhoeae genome were constructed. Several immunogenic oligopeptides were identified using polyclonal rabbit antibodies against N. gonorrhoeae. Corresponding full-length proteins of the identified oligopeptides were expressed and their immunogenic character was verified by ELISA. The immunogenic character of six proteins was identified for the first time. Additional 13 proteins were verified as immunogenic proteins in N. gonorrhoeae. PMID- 26859669 TI - Impact of bladder volume on radiation dose to the rectum in the definitive treatment of prostate cancer. AB - BACKGROUND AND OBJECTIVE: Our group created and routinely reviewed a dedicated prostate intensity-modulated radiation therapy (IMRT) delivery program. Previously, a retrospective review of our experience demonstrated that a larger bladder volume reduced radiation dose to the rectum. We conducted an observational study to confirm this relationship. METHODS: Men receiving definitive radiation for prostate cancer were eligible for the study. Eligible patients received 2 computed axial tomography (CT) scans on the day of their planning CT scan: 1 with a full bladder and 1 with an empty bladder. On each CT data set, the prostate, rectum, bladder, penile bulb, and femoral heads were contoured. 2 IMRT plans were completed on each dataset: 1 by a medical dosimetrist and 1 by a medical physicist. The study plans targeted the prostate to 79.2 Gray (Gy) while respecting predefined dose tolerances to the other contoured structures. Rectal doses were compared on empty and full bladder CT data sets. RESULTS: From June 29, 2010 to December 14, 2011, 17 full bladder data sets and 15 empty bladder data sets were available for analysis. Median change in bladder volume was 63 ml. Full vs empty bladder set-up was associated with a statistically significant reduction in the mean rectal dose of 25.41 Gy vs 27.6 Gy (?? = .031). LIMITATIONS: Small sample size and small variations in bladder volumes. CONCLUSIONS: A greater bladder volume resulted in a reduced mean dose to the rectum irrespective of planning method. PMID- 26859670 TI - Treatment outcomes in stage IIIA non-small-cell lung cancer in a community cancer center. AB - BACKGROUND: Treatment outcomes for non-small-cell lung cancer (NSCLC) patients diagnosed at stage IIIA have been analyzed in many studies, which generally involve patients younger and healthier than the average patient with this disease. OBJECTIVE: To analyze demographics and treatment outcomes in patients with stage IIIA NSCLC at a community cancer center. METHODS: We reviewed charts of 226 patients diagnosed with stage IIIA NSCLC from January 2003 to December 2008 treated at our community cancer center. Results Median overall survival for all patients and sequentially and concurrently treated chemoradiation patients were 18 months, and 18 months, and 20 months, respectively. Median overall survival for women and men was 24 months and 16 months, respectively. RESULTS: Median overall survival for all patients and sequentially and concurrently treated chemoradiation patients were 18 months, and 18 months, and 20 months, respectively. Median overall survival for women and men was 24 months and 16 months, respectively. LIMITATIONS: Study design was retrospective and some medical records were not available. However, this population is likely representative of patients treated in similar settings. CONCLUSIONS: In our population, advanced age and male gender were associated with lower median survival. Responses to concurrent and sequential chemoradiation seemed to differ based on age group, which may be useful as a prognostic guideline for similar populations. PMID- 26859671 TI - Life-threatening hypoglycemia resulting from a nonislet cell tumor. AB - Nonislet cell tumor-induced hypoglycemia (NICTH), also known as Doege-Potter syndrome, is a rare paraneoplastic syndrome seen in association with various nonpancreatic tumors, benign and malignant, and comprising mesenchymal, vascular, or epithelial cell types. We report a case of recurrent life-threatening hypoglycemia from a large pelvic solitary fibrous tumor. PMID- 26859667 TI - Plasmid Characterization and Chromosome Analysis of Two netF+ Clostridium perfringens Isolates Associated with Foal and Canine Necrotizing Enteritis. AB - The recent discovery of a novel beta-pore-forming toxin, NetF, which is strongly associated with canine and foal necrotizing enteritis should improve our understanding of the role of type A Clostridium perfringens associated disease in these animals. The current study presents the complete genome sequence of two netF-positive strains, JFP55 and JFP838, which were recovered from cases of foal necrotizing enteritis and canine hemorrhagic gastroenteritis, respectively. Genome sequencing was done using Single Molecule, Real-Time (SMRT) technology PacBio and Illumina Hiseq2000. The JFP55 and JFP838 genomes include a single 3.34 Mb and 3.53 Mb chromosome, respectively, and both genomes include five circular plasmids. Plasmid annotation revealed that three plasmids were shared by the two newly sequenced genomes, including a NetF/NetE toxins-encoding tcp-conjugative plasmid, a CPE/CPB2 toxins-encoding tcp-conjugative plasmid and a putative bacteriocin-encoding plasmid. The putative beta-pore-forming toxin genes, netF, netE and netG, were located in unique pathogenicity loci on tcp-conjugative plasmids. The C. perfringens JFP55 chromosome carries 2,825 protein-coding genes whereas the chromosome of JFP838 contains 3,014 protein-encoding genes. Comparison of these two chromosomes with three available reference C. perfringens chromosome sequences identified 48 (~247 kb) and 81 (~430 kb) regions unique to JFP55 and JFP838, respectively. Some of these divergent genomic regions in both chromosomes are phage- and plasmid-related segments. Sixteen of these unique chromosomal regions (~69 kb) were shared between the two isolates. Five of these shared regions formed a mosaic of plasmid-integrated segments, suggesting that these elements were acquired early in a clonal lineage of netF-positive C. perfringens strains. These results provide significant insight into the basis of canine and foal necrotizing enteritis and are the first to demonstrate that netF resides on a large and unique plasmid-encoded locus. PMID- 26859672 TI - Drug-induced immune hemolytic anemia associated with albumin-bound paclitaxel. AB - Drug-induced immune hemolytic anemia (DIIHA) is rare, with only 1 patient in 1 million affected by the condition.1 Garratty identified 125 drugs indicated in DIIHA of which 11% were antineoplastic agents, and neither paclitaxel nor albumin bound paclitaxel were included.2 In addition, we did not find any reports in our own search of the literature. Taxanes are known to cause anemia as a result of their myelosuppressive effects, but an immune hemolysis is rare. To our knowledge, we present here the first case of DIIHA with nab-paclitaxel. PMID- 26859673 TI - Covered versus Uncovered Self-Expandable Metal Stents for Managing Malignant Distal Biliary Obstruction: A Meta-Analysis. AB - AIM: To compare the efficacy of using covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (UCSEMSs) to treat objective jaundice caused by an unresectable malignant tumor. METHODS: We performed a comprehensive electronic search from 1980 to May 2015. All randomized controlled trials comparing the use of CSEMSs and UCSEMSs to treat malignant distal biliary obstruction were included. RESULTS: The analysis included 1417 patients enrolled in 14 trials. We did not detect significant differences between the UCSEMS group and the CSEMS group in terms of cumulative stent patency (hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.19-4.53; p = 0.93, I2 = 0%), patient survival (HR 0.77, 95% CI 0.05-10.87; p = 0.85, I2 = 0%), overall stent dysfunction (relative ratio (RR) 0.85, M-H, random, 95% CI 0.57-1.25; p = 0.83, I2 = 63%), the overall complication rate (RR 1.26, M-H, fixed, 95% CI 0.94-1.68; p = 0.12, I2 = 0%) or the change in serum bilirubin (weighted mean difference (WMD) -0.13, IV fixed, 95% CI 0.56-0.3; p = 0.55, I2 = 0%). However, we did detect a significant difference in the main causes of stent dysfunction between the two groups. In particular, the CSEMS group exhibited a lower rate of tumor ingrowth (RR 0.25, M H, random, 95% CI 0.12-0.52; p = 0.002, I2 = 40%) but a higher rate of tumor overgrowth (RR 1.76, M-H, fixed, 95% CI 1.03-3.02; p = 0.04, I2 = 0%). Patients with CSEMSs also exhibited a higher migration rate (RR 9.33, M-H, fixed, 95% CI 2.54-34.24; p = 0.008, I2 = 0%) and a higher rate of sludge formation (RR 2.47, M H, fixed, 95% CI 1.36-4.50; p = 0.003, I2 = 0%). CONCLUSIONS: Our meta-analysis indicates that there is no significant difference in primary stent patency and stent dysfunction between CSEMSs and UCSEMSs during the period from primary stent insertion to primary stent dysfunction or patient death. However, when taking further management for occluded stents into consideration, CSEMSs is a better choice for patients with malignant biliary obstruction due to their removability. PMID- 26859675 TI - Impact of Cattaneo-Christov Heat Flux in Jeffrey Fluid Flow with Homogeneous Heterogeneous Reactions. AB - Two-dimensional stretched flow of Jeffrey fluid in view of Cattaneo-Christov heat flux is addressed. Effects of homogeneous-heterogeneous reactions are also considered. Suitable transformations are used to form ordinary differential equations. Convergent series solutions are computed. Impact of significant parameters on the velocity, temperature, concentration and skin friction coefficient is addressed. Analysis of thermal relaxation is made. The obtained results show that ratio of relaxation to retardation times and Deborah number have inverse relation for velocity profile. Temperature distribution has decreasing behavior for Prandtl number and thermal relaxation time. Also concentration decreases for larger values of strength of homogeneous reaction parameter while it increases for strength of heterogeneous reaction parameter. PMID- 26859674 TI - IL-15 Superagonist Expands mCD8+ T, NK and NKT Cells after Burn Injury but Fails to Improve Outcome during Burn Wound Infection. AB - BACKGROUND: Severely burned patients are highly susceptible to opportunistic infections and sepsis, owing to the loss of the protective skin barrier and immunological dysfunction. Interleukin-15 (IL-15) belongs to the IL-2 family of common gamma chain cytokines and stimulates the proliferation and activation of T (specifically memory CD8), NK and NKT cells. It has been shown to preserve T cell function and improve survival during cecal ligation and puncture (CLP)-induced sepsis in mice. However, the therapeutic efficacy of IL-15 or IL-15 superagonist (SA) during infection after burn injury has not been evaluated. Moreover, very few, if any, studies have examined, in detail, the effect of burn injury and infection on the adaptive immune system. Thus, we examined the effect of burn and sepsis on adaptive immune cell populations and the effect of IL-15 SA treatment on the host response to infection. METHODS: Mice were subjected to a 35% total body surface area burn, followed by wound infection with Pseudomonas aeruginosa. In some experiments, IL-15 SA was administered after burn injury, but before infection. Leukocytes in spleen, liver and peritoneal cavity were characterized using flow cytometry. Bacterial clearance, organ injury and survival were also assessed. RESULTS: Burn wound infection led to a significant decline in total white blood cell and lymphocyte counts and induced organ injury and sepsis. Burn injury caused decline in CD4+ and CD8+ T cells in the spleen, which was worsened by infection. IL-15 treatment inhibited this decline and significantly increased cell numbers and activation, as determined by CD69 expression, of CD4+, CD8+, B, NK and NKT cells in the spleen and liver after burn injury. However, IL-15 SA treatment failed to prevent burn wound sepsis-induced loss of CD4+, CD8+, B, NK and NKT cells and failed to improve bacterial clearance and survival. CONCLUSION: Cutaneous burn injury and infection cause significant adaptive immune dysfunction. IL-15 SA does not augment host resistance to burn wound sepsis in mice despite inducing proliferation and activation of lymphocyte subsets. PMID- 26859676 TI - AKT1E17K Is Oncogenic in Mouse Lung and Cooperates with Chemical Carcinogens in Inducing Lung Cancer. AB - The hotspot AKT1E17K mutation in the pleckstrin homology domain of AKT1 occurs in approximately 0.6-2% of human lung cancers. Recently, we have demonstrated that AKT1E17K transforms immortalized human bronchial cells. Here by use of a transgenic Cre-inducible murine strain in the wild type Rosa26 (R26) locus (R26 AKT1E17K mice) we demonstrate that AKT1E17K is a bona-fide oncogene and plays a role in the development of lung cancer in vivo. In fact, we report that mutant AKT1E17K induces bronchial and/or bronchiolar hyperplastic lesions in murine lung epithelium, which progress to frank carcinoma at very low frequency, and accelerates tumor formation induced by chemical carcinogens. In conclusion, AKT1E17K induces hyperplasia of mouse lung epithelium in vivo and cooperates with urethane to induce the fully malignant phenotype. PMID- 26859677 TI - Histophilus somni Stimulates Expression of Antiviral Proteins and Inhibits BRSV Replication in Bovine Respiratory Epithelial Cells. AB - Our previous studies showed that bovine respiratory syncytial virus (BRSV) followed by Histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. However, microarray analysis revealed the treatment of bovine alveolar type 2 (BAT2) epithelial cells with H. somni concentrated culture supernatant (CCS) stimulated up-regulation of four antiviral protein genes as compared with BRSV infection or dual treatment. This suggested that inhibition of viral infection, rather than synergy, may occur if the bacterial infection occurred before the viral infection. Viperin (or radical S-adenosyl methionine domain containing 2--RSAD2) and ISG15 (IFN-stimulated gene 15--ubiquitin-like modifier) were most up regulated. CCS dose and time course for up-regulation of viperin protein levels were determined in treated bovine turbinate (BT) upper respiratory cells and BAT2 lower respiratory cells by Western blotting. Treatment of BAT2 cells with H. somni culture supernatant before BRSV infection dramatically reduced viral replication as determined by qRT PCR, supporting the hypothesis that the bacterial infection may inhibit viral infection. Studies of the role of the two known H. somni cytotoxins showed that viperin protein expression was induced by endotoxin (lipooligosaccharide) but not by IbpA, which mediates alveolar permeability and H. somni invasion. A naturally occurring IbpA negative asymptomatic carrier strain of H. somni (129Pt) does not cause BAT2 cell retraction or permeability of alveolar cell monolayers, so lacks virulence in vitro. To investigate initial steps of pathogenesis, we showed that strain 129Pt attached to BT cells and induced a strong viperin response in vitro. Thus colonization of the bovine upper respiratory tract with an asymptomatic carrier strain lacking virulence may decrease viral infection and the subsequent enhancement of bacterial respiratory infection in vivo. PMID- 26859678 TI - Functional Assessments Used by Occupational Therapists with Older Adults at Risk of Activity and Participation Limitations: A Systematic Review. AB - INTRODUCTION: The use of functional assessments to evaluate patient change is complicated by a lack of consensus as to which assessment is most suitable for use with older adults. OBJECTIVE: To identify and appraise the properties of assessments used to evaluate functional abilities in older adults. METHODS: A systematic review of randomised controlled trials of occupational therapy interventions was conducted up to 2012 to identify assessments used to measure function. Two authors screened and extracted data independently. A second search then identified papers investigating measurement properties of each assessment. Studies from the second search were included if: i) published in English, ii) the assessment was not modified from its original published form, iii) study aim was to evaluate the quality of the tool, iv) and was original research. Translated versions of assessments were excluded. Measurement quality was rated using the COSMIN checklist and Terwee criteria. RESULTS: Twenty-eight assessments were identified from the systematic search of occupational therapy interventions provided to older adults. Assessments were of varied measurement quality and many had been adapted (although still evaluated as though the original tool had been administered) potentially altering the conclusions drawn about measurement quality. Synthesis of best evidence established 15 functional assessments have not been tested in an older adult population. CONCLUSIONS: The Functional Autonomy Measurement System (SMAF) appears to be a promising assessment for use with older adults. Only two tools (the SMAF and the Assessment of Motor and Process Skills (AMPS)) were deemed to be responsive to change when applied to older adults. Health professionals should use functional assessments that have been validated with their population and in their setting. There are reliable and valid assessments to capture the functional performance of older adults in community and hospital settings, although further refinement of these assessments may be necessary. PMID- 26859679 TI - Association of rituximab with graphene oxide confers direct cytotoxicity for CD20 positive lymphoma cells. AB - Non-Hodgkin lymphoma (NHL) is one of the most common hematologic malignancies among adults for which the chimeric monoclonal anti-CD20 antibody (Ab) rituximab (RTX) is used as first-line therapy. As RTX itself is not directly cytotoxic but relies on host immune effector mechanisms or chemotherapeutic agents to attack target cells, its therapeutic capacity may become limited when host effector mechanisms are compromised. Currently, refractory disease and relapse with NHL are still common, highlighting the need for novel anti-CD20 antibody strategies with superior therapeutic efficacy over current protocols. We hypothesized that making RTX directly cytotoxic might improve the therapeutic efficacy. Graphene oxide (GO) has recently emerged as a highly attractive nanomaterial for biomedical applications; and several studies have reported cytotoxic effect of GO on benign and malignant cells in vitro. Herein, we report that RTX can be stably associated with GO, and that GO-associated RTX (RTX/GO) demonstrates remarkably high avidity for CD20. Binding of GO-associated RTX to CD20-positive lymphoma cells induces CD20 capping and target cell death through an actin dependent mechanism. In vivo, GO-associated RTX, but not free RTX, quickly eliminates high grade lymphomas in the absence of host effector mechanisms in a xenograft lymphoma mouse model. Our findings represent the first demonstration of using GO associated antibody as effective cytotoxic therapy for human B cell malignancies in the absence of chemotherapy, and these findings could have important clinical implications. PMID- 26859680 TI - Marked enhancement of lysosomal targeting and efficacy of ErbB2-targeted drug delivery by HSP90 inhibition. AB - Targeted delivery of anticancer drugs to tumor cells using monoclonal antibodies against oncogenic cell surface receptors is an emerging therapeutic strategy. These strategies include drugs directly conjugated to monoclonal antibodies through chemical linkers (Antibody-Drug Conjugates, ADCs) or those encapsulated within nanoparticles that in turn are conjugated to targeting antibodies (Antibody-Nanoparticle Conjugates, ANPs). The recent FDA approval of the ADC Trastuzumab-TDM1 (Kadcyla; Genentech; San Francisco) for the treatment of ErbB2 overexpressing metastatic breast cancer patients has validated the strong potential of these strategies. Even though the activity of ANPs and ADCs is dependent on lysosomal traffic, the roles of the endocytic route traversed by the targeted receptor and of cancer cell-specific alterations in receptor dynamics on the efficiency of drug delivery have not been considered in these new targeted therapies. For example, constitutive association with the molecular chaperone HSP90 is thought to either retard ErbB2 endocytosis or to promote its recycling, traits undesirable for targeted therapy with ANPs and ADCs. HSP90 inhibitors are known to promote ErbB2 ubiquitination, targeting to lysosome and degradation. We therefore hypothesized that ErbB2-targeted drug delivery using Trastuzumab conjugated nanoparticles could be significantly improved by HSP90 inhibitor promoted lysosomal traffic of ErbB2. Studies reported here validate this hypothesis and demonstrate, both in vitro and in vivo, that HSP90 inhibition facilitates the intracellular delivery of Trastuzumab-conjugated ANPs carrying a model chemotherapeutic agent, Doxorubicin, specifically into ErbB2-overexpressing breast cancer cells, resulting in improved antitumor activity. These novel findings highlight the need to consider oncogene-specific alterations in receptor traffic in the design of targeted drug delivery strategies. We suggest that combination of agents that enhance receptor endocytosis and lysosomal routing can provide a novel strategy to significantly improve therapy with ANPs and ADCs. PMID- 26859681 TI - Spatially- and temporally-controlled postnatal p53 knockdown cooperates with embryonic Schwann cell precursor Nf1 gene loss to promote malignant peripheral nerve sheath tumor formation. AB - Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive sarcomas that arise sporadically or in association with the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome. In individuals with NF1, MPNSTs are hypothesized to arise from Nf1-deficient Schwann cell precursor cells following the somatic acquisition of secondary cooperating genetic mutations (e.g., p53 loss). To model this sequential genetic cooperativity, we coupled somatic lentivirus-mediated p53 knockdown in the adult right sciatic nerve with embryonic Schwann cell precursor Nf1 gene inactivation in two different Nf1 conditional knockout mouse strains. Using this approach, ~60% of mice with Periostin-Cre-mediated Nf1 gene inactivation (Periostin-Cre; Nf1(flox/flox) mice) developed tumors classified as low-grade MPNSTs following p53 knockdown (mean, 6 months). Similarly, ~70% of Nf1+/- mice with GFAP-Cre-mediated Nf1 gene inactivation (GFAP-Cre; Nf1(flox/null) mice) developed low-grade MPNSTs following p53 knockdown (mean, 3 months). In addition, wild-type and Nf1+/- mice with GFAP-Cre-mediated Nf1 loss develop MPNSTs following somatic p53 knockout with different latencies, suggesting potential influences of Nf1+/- stromal cells in MPNST pathogenesis. Collectively, this new MPNST model system permits the analysis of somatically acquired events as well as tumor microenvironment signals that potentially cooperate with Nf1 loss in the development and progression of this deadly malignancy. PMID- 26859683 TI - Next-generation sequencing reveals somatic mutations that confer exceptional response to everolimus. AB - BACKGROUND: Given the modest responses to everolimus, a mTOR inhibitor, in multiple tumor types, there is a pressing need to identify predictive biomarkers for this drug. Using targeted ultra-deep sequencing, we aimed to explore genomic alterations that confer extreme sensitivity to everolimus. RESULTS: We collected formalin-fixed paraffin-embedded tumor/normal pairs from 39 patients (22 with exceptional clinical benefit, 17 with no clinical benefit) who were treated with everolimus across various tumor types (13 gastric cancers, 15 renal cell carcinomas, 2 thyroid cancers, 2 head and neck cancer, and 7 sarcomas). Ion AmpliSeqTM Comprehensive Cancer Panel was used to identify alterations across all exons of 409 target genes. Tumors were sequenced to a median coverage of 552x. Cancer genomes are characterized by 219 somatic single-nucleotide variants (181 missense, 9 nonsense, 7 splice-site) and 22 frameshift insertions/deletions, with a median of 2.1 mutations per Mb (0 to 12.4 mutations per Mb). Overall, genomic alterations with activating effect on mTOR signaling were identified in 10 of 22 (45%) patients with clinical benefit and these include MTOR, TSC1, TSC2, NF1, PIK3CA and PIK3CG mutations. Recurrently mutated genes in chromatin remodeling genes (BAP1; n = 2, 12%) and receptor tyrosine kinase signaling (FGFR4; n = 2, 12%) were noted only in patients without clinical benefit. CONCLUSIONS: Regardless of different cancer types, mTOR-pathway-activating mutations confer sensitivity to everolimus. Targeted sequencing of mTOR pathway genes facilitates identification of potential candidates for mTOR inhibitors. PMID- 26859682 TI - Quantification of unmethylated Alu (QUAlu): a tool to assess global hypomethylation in routine clinical samples. AB - Hypomethylation of DNA is a hallmark of cancer and its analysis as tumor biomarker has been proposed, but its determination in clinical settings is hampered by lack of standardized methodologies. Here, we present QUAlu (Quantification of Unmethylated Alu), a new technique to estimate the Percentage of UnMethylated Alu (PUMA) as a surrogate for global hypomethylation. QUAlu consists in the measurement by qPCR of Alu repeats after digestion of genomic DNA with isoschizomers with differential sensitivity to DNA methylation. QUAlu performance has been evaluated for reproducibility, trueness and specificity, and validated by deep sequencing. As a proof of use, QUAlu has been applied to a broad variety of pathological examination specimens covering five cancer types. Major findings of the preliminary application of QUAlu to clinical samples include: (1) all normal tissues displayed similar PUMA; (2) tumors showed variable PUMA with the highest levels in lung and colon and the lowest in thyroid cancer; (3) stools from colon cancer patients presented higher PUMA than those from control individuals; (4) lung squamous cell carcinomas showed higher PUMA than lung adenocarcinomas, and an increasing hypomethylation trend associated with smoking habits. In conclusion, QUAlu is a simple and robust method to determine Alu hypomethylation in human biospecimens and may be easily implemented in research and clinical settings. PMID- 26859684 TI - Activation of the PD-1/PD-L1 immune checkpoint confers tumor cell chemoresistance associated with increased metastasis. AB - The ability of tumor cells to avoid immune destruction (immune escape) as well as their acquired resistance to anti-cancer drugs constitute important barriers to the successful management of cancer. Interaction between the Programmed Death Ligand 1 (PD-L1) on the surface of tumor cells with the Programmed Death-1 (PD-1) receptor on cytotoxic T lymphocytes leads to inactivation of these immune effectors and, consequently, immune escape. Here we show that the PD-1/PD-L1 axis also leads to tumor cell resistance to conventional chemotherapeutic agents. Using a panel of PD-L1-expressing human and mouse breast and prostate cancer cell lines, we found that incubation of breast and prostate cancer cells in the presence of purified recombinant PD-1 resulted in resistance to doxorubicin and docetaxel as determined using clonogenic survival assays. Co-culture with PD-1 expressing Jurkat T cells also promoted chemoresistance and this was prevented by antibody blockade of either PD-L1 or PD-1 or by silencing of the PD-L1 gene. Moreover, inhibition of the PD-1/PD-L1 axis using anti-PD-1 antibody enhanced doxorubicin chemotherapy to inhibit metastasis in a syngeneic mammary orthotopic mouse model of metastatic breast cancer. To further investigate the mechanism of tumor cell survival advantage upon PD-L1 ligation, we show that exposure to rPD-1 promoted ERK and mTOR growth and survival pathways leading to increased cell proliferation. Overall, the findings of this study indicate that combinations of chemotherapy and immune checkpoint blockade may limit chemoresistance and progression to metastatic disease. PMID- 26859685 TI - OMIP-031: Immunologic checkpoint expression on murine effector and memory T-cell subsets. PMID- 26859686 TI - Identification of Gene Modules Associated with Low Temperatures Response in Bambara Groundnut by Network-Based Analysis. AB - Bambara groundnut (Vigna subterranea (L.) Verdc.) is an African legume and is a promising underutilized crop with good seed nutritional values. Low temperature stress in a number of African countries at night, such as Botswana, can effect the growth and development of bambara groundnut, leading to losses in potential crop yield. Therefore, in this study we developed a computational pipeline to identify and analyze the genes and gene modules associated with low temperature stress responses in bambara groundnut using the cross-species microarray technique (as bambara groundnut has no microarray chip) coupled with network based analysis. Analyses of the bambara groundnut transcriptome using cross species gene expression data resulted in the identification of 375 and 659 differentially expressed genes (p<0.01) under the sub-optimal (23 degrees C) and very sub-optimal (18 degrees C) temperatures, respectively, of which 110 genes are commonly shared between the two stress conditions. The construction of a Highest Reciprocal Rank-based gene co-expression network, followed by its partition using a Heuristic Cluster Chiseling Algorithm resulted in 6 and 7 gene modules in sub-optimal and very sub-optimal temperature stresses being identified, respectively. Modules of sub-optimal temperature stress are principally enriched with carbohydrate and lipid metabolic processes, while most of the modules of very sub-optimal temperature stress are significantly enriched with responses to stimuli and various metabolic processes. Several transcription factors (from MYB, NAC, WRKY, WHIRLY & GATA classes) that may regulate the downstream genes involved in response to stimulus in order for the plant to withstand very sub-optimal temperature stress were highlighted. The identified gene modules could be useful in breeding for low-temperature stress tolerant bambara groundnut varieties. PMID- 26859687 TI - Bone biology-related gingival transcriptome in ageing and periodontitis in non human primates. AB - AIM: Cellular and molecular immunoinflammatory changes in gingival tissues drive alveolar bone loss in periodontitis. Since ageing is a risk factor for periodontitis, we sought to identify age-related gingival transcriptome changes associated with bone metabolism in both healthy and in naturally occurring periodontitis. MATERIALS AND METHODS: Adult (12-16 years) and aged (18-23 years) non-human primates (M. mulatta) (n = 24) were grouped into healthy and periodontitis. Gingival tissue samples were obtained and subjected to microarray analysis using the Gene Chip Macaque Genome Array. Gene expression profiles involved in osteoclast/osteoblast proliferation, adhesion and function were evaluated and compared across and between the age groups. QPCR was also performed on selected genes to validate microarray data. RESULTS: Healthy aged tissues showed a gene profile expression that suggest enhancement of osteoclastic adhesion, proliferation/survival and function (SPP1, TLR4, MMP8 and TFEC) and impaired osteoblastic activity (SMEK3P and SMAD5). The gingival transcriptome in both adult and aged animals with naturally occurring periodontitis (FOS, IL6, TLR4, MMP9, MMP10 and SPP1 genes) was consistent with a local inflammatory response driving towards bone/connective tissue destruction. CONCLUSION: A pro osteoclastogenic gingival transcriptome is associated with periodontitis irrespective of age; however; a greater bone-destructive molecular environment is associated with ageing in healthy tissues. PMID- 26859690 TI - Population Viability and Vital Rate Sensitivity of an Endangered Avian Cooperative Breeder, the White-Breasted Thrasher (Ramphocinclus brachyurus). AB - Social behaviors can significantly affect population viability, and some behaviors might reduce extinction risk. We used population viability analysis to evaluate effects of past and proposed habitat loss on the White-breasted Thrasher (Ramphocinclus brachyurus), a cooperatively breeding songbird with a global population size of <2000 individuals. We used an individual-based approach to build the first demographic population projection model for this endangered species, parameterizing the model with data from eight years of field study before and after habitat loss within the stronghold of the species' distribution. The recent habitat loss resulted in an approximately 18% predicted decline in population size; this estimate was mirrored by a separate assessment using occupancy data. When mortality rates remained close to the pre-habitat loss estimate, quasi-extinction probability was low under extant habitat area, but increased with habitat loss expected after current plans for resort construction are completed. Post-habitat loss mortality rate estimates were too high for projected populations to persist. Vital rate sensitivity analyses indicated that population growth rate and population persistence were most sensitive to juvenile mortality. However, observed values for adult mortality were closest to the threshold value above which populations would crash. Adult mortality, already relatively low, may have the least capacity to change compared to other vital rates, whereas juvenile mortality may have the most capacity for improvement. Results suggest that improving mortality estimates and determining the cause(s) of juvenile mortality should be research priorities. Despite predictions that aspects of cooperative systems may result in variation in reproduction or juvenile mortality being the most sensitive vital rates, adult mortality was the most sensitive in half of the demographic models of other avian cooperative breeders. Interestingly, vital rate sensitivity differed by model type. However, studies that explicitly modeled the species' cooperative breeding system found reproduction to be the most sensitive rate. PMID- 26859688 TI - Cost-Effectiveness of a National Initiative to Improve Hand Hygiene Compliance Using the Outcome of Healthcare Associated Staphylococcus aureus Bacteraemia. AB - BACKGROUND: The objective is to estimate the incremental cost-effectiveness of the Australian National Hand Hygiene Inititiave implemented between 2009 and 2012 using healthcare associated Staphylococcus aureus bacteraemia as the outcome. Baseline comparators are the eight existing state and territory hand hygiene programmes. The setting is the Australian public healthcare system and 1,294,656 admissions from the 50 largest Australian hospitals are included. METHODS: The design is a cost-effectiveness modelling study using a before and after quasi experimental design. The primary outcome is cost per life year saved from reduced cases of healthcare associated Staphylococcus aureus bacteraemia, with cost estimated by the annual on-going maintenance costs less the costs saved from fewer infections. Data were harvested from existing sources or were collected prospectively and the time horizon for the model was 12 months, 2011-2012. FINDINGS: No useable pre-implementation Staphylococcus aureus bacteraemia data were made available from the 11 study hospitals in Victoria or the single hospital in Northern Territory leaving 38 hospitals among six states and territories available for cost-effectiveness analyses. Total annual costs increased by $2,851,475 for a return of 96 years of life giving an incremental cost-effectiveness ratio (ICER) of $29,700 per life year gained. Probabilistic sensitivity analysis revealed a 100% chance the initiative was cost effective in the Australian Capital Territory and Queensland, with ICERs of $1,030 and $8,988 respectively. There was an 81% chance it was cost effective in New South Wales with an ICER of $33,353, a 26% chance for South Australia with an ICER of $64,729 and a 1% chance for Tasmania and Western Australia. The 12 hospitals in Victoria and the Northern Territory incur annual on-going maintenance costs of $1.51M; no information was available to describe cost savings or health benefits. CONCLUSIONS: The Australian National Hand Hygiene Initiative was cost-effective against an Australian threshold of $42,000 per life year gained. The return on investment varied among the states and territories of Australia. PMID- 26859691 TI - A UDP-glucosyltransferase functions in both acylphloroglucinol glucoside and anthocyanin biosynthesis in strawberry (Fragaria * ananassa). AB - Physiologically active acylphloroglucinol (APG) glucosides were recently found in strawberry (Fragaria sp.) fruit. Although the formation of the APG aglycones has been clarified, little is known about APG glycosylation in plants. In this study we functionally characterized ripening-related glucosyltransferase genes in Fragaria by comprehensive biochemical analyses of the encoded proteins and by a RNA interference (RNAi) approach in vivo. The allelic proteins UGT71K3a/b catalyzed the glucosylation of diverse hydroxycoumarins, naphthols and flavonoids as well as phloroglucinols, enzymatically synthesized APG aglycones and pelargonidin. Total enzymatic synthesis of APG glucosides was achieved by co incubation of recombinant dual functional chalcone/valerophenone synthase and UGT71K3 proteins with essential coenzyme A esters and UDP-glucose. An APG glucoside was identified in strawberry fruit which has not yet been reported in other plants. Suppression of UGT71K3 activity in transient RNAi-silenced fruits led to a loss of pigmentation and a substantial decrease of the levels of various APG glucosides and an anthocyanin. Metabolite analyses of transgenic fruits confirmed UGT71K3 as a UDP-glucose:APG glucosyltransferase in planta. These results provide the foundation for the breeding of fruits with improved health benefits and for the biotechnological production of bioactive natural products. PMID- 26859692 TI - Fetomaternal Hemorrhage: Mostly a Hidden Hazard. PMID- 26859694 TI - Cystoseira usneoides: A Brown Alga Rich in Antioxidant and Anti-inflammatory Meroditerpenoids. AB - Twelve new meroditerpenoids, 1-12, along with eight known compounds, have been isolated from the brown alga Cystoseira usneoides collected off the coast of Tarifa (Spain). The structures of the new metabolites have been established by spectroscopic techniques. All of the new compounds consist of a toluhydroquinone derived nucleus linked to a regular diterpenoid moiety, which can either be acyclic or contain an ether ring. Most structural diversity arises from the presence of different oxygenated functionalities and unsaturations along the two terminal isoprenoid units of the diterpene backbone. Twelve of the isolated meroditerpenes have been tested in antioxidant assays. All of them have shown radical-scavenging activity. The most active compounds were cystodiones G (1) and H (2), 11-hydroxyamentadione (15), and amentadione (16), which exhibited antioxidant activities in the range of 77-87% that of the Trolox standard. In anti-inflammatory assays, cystodiones G (1) and M (6), cystone C (9), 11 hydroxyamentadione (15), and amentadione (16) showed significant activity as inhibitors of the production of the proinflammatory cytokine TNF-alpha in LPS stimulated THP-1 human macrophages. PMID- 26859693 TI - Mismatch repair status in patients with primary operable colorectal cancer: associations with the local and systemic tumour environment. AB - BACKGROUND: Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is associated with a conspicuous local immune infiltrate; however, its relationship with systemic inflammatory responses remains to be determined. The present study aims to examine the relationships and prognostic value of assessment of the local and systemic environment in the context of MMR status in patients with CRC. METHODS: The relationship between MMR status, determined using immunohistochemistry, and the local inflammatory cell infiltrate, differential white cell count, neutrophil : platelet score (NPS), neutrophil : lymphocyte ratio and modified Glasgow Prognostic Score (mGPS), and cancer-specific survival was examined in 228 patients undergoing resection of stage I-III CRC. RESULTS: Thirty-five patients (15%) had dMMR CRC. Mismatch repair deficiency was associated with a higher density of CD3(+), CD8(+) and CD45R0(+) T lymphocytes within the cancer cell nests and an elevated mGPS (mGPS2: 23% vs 9%, P=0.007) and NPS (NPS2: 19% vs 3%, P=0.001). CD3(+) density (P<0.001), mGPS (P=0.01) and NPS (P=0.042) were associated with survival independent of MMR status (P=0.367) and stratified 5-year survival of patients with MMR-competent CRC from 94% to 67%, 83% to 46% and 78% to 60% respectively. CONCLUSIONS: Mismatch repair deficiency was associated with local and systemic environments, and in comparison with their assessment, dMMR had relatively poor prognostic value in patients with primary operable CRC. In addition to MMR status, local and systemic inflammatory responses should be assessed in these patients. PMID- 26859695 TI - Contraceptive efficacy of recombinant fusion protein comprising zona pellucida glycoprotein-3 fragment and gonadotropin releasing hormone. AB - Contraceptive vaccines have been used for the management of wildlife population. In the present study, we have examined the contraceptive potential of Escherichia coli-expressed recombinant fusion protein comprising of 'promiscuous' T cell epitope of tetanus toxoid [TT; amino acid (aa) residues 830-844] followed by dilysine linker (KK), dog ZP3 fragment (aa residues 307-346), triglycine spacer (GGG), T cell epitope of bovine RNase (bRNase; aa residues 94-104), GnRH, T cell epitope of circumsporozoite protein of Plasmodium falciparum (CSP; aa residues 362-383), and GnRH. SDS-PAGE analysis of the purified refolded protein revealed a dominant ~12 kDa band, which in Western blot reacted with mouse polyclonal antibodies against dog ZP3 fragment and mouse monoclonal antibodies against GnRH. Immunization of female FvB/J mice following two booster schedule with the above recombinant protein supplemented with alum led to high antibody titres against the immunogen as well as ZP3 and GnRH as determined by ELISA. The immune sera reacted with zona pellucida of mouse oocyte and also inhibited in-vitro fertilization. The qRT-PCR studies showed decrease in the ovarian GnRH receptor in mice immunized with the recombinant fusion protein. Mating studies revealed high contraceptive efficacy of the recombinant protein as in two independent experiments, 90% of the immunized female mice failed to conceive. Following one booster immunization schedule, 50% of the immunized female mice failed to conceive. However, in adjuvanted controls, all the female mice became pregnant. To conclude, the recombinant protein described herein has a good potential to be developed as candidate contraceptive vaccine. PMID- 26859696 TI - Therapeutic and recreational methadone cardiotoxicity. AB - Several classes of drugs have been associated with an increased risk of cardiovascular disease and occurrence of arrhythmias potentially involved in sudden deaths in chronic users even at therapeutic doses. The study presented herein focuses on pathological changes involving the heart possibly due to methadone use. 60 cases were included in the study in total and were divided into three groups (therapeutic methadone users: 20 cases, recreational methadone users: 20 cases, and sudden death group in subjects who had never taken methadone: 20 cases). Autopsies, histology, biochemistry and toxicology were performed in all cases. Macroscopic and microscopic investigation results in therapeutic methadone users were similar to those observed in sudden, unexpected deaths in non-methadone users. In recreational methadone consumers, macroscopic and microscopic examination of the heart failed to provide results consistent with acute or chronic myocardial or coronary damage, thereby corroborating the hypothesis of death most likely following respiratory depression. PMID- 26859697 TI - Predicting Single-Layer Technetium Dichalcogenides (TcX2, X = S, Se) with Promising Applications in Photovoltaics and Photocatalysis. AB - One of the least known compounds among transition metal dichalcogenides (TMDCs) is the layered triclinic technetium dichalcogenides (TcX2, X = S, Se). In this work, we systematically study the structural, mechanical, electronic, and optical properties of TcS2 and TcSe2 monolayers based on density functional theory (DFT). We find that TcS2 and TcSe2 can be easily exfoliated in a monolayer form because their formation and cleavage energy are analogous to those of other experimentally realized TMDCs monolayer. By using a hybrid DFT functional, the TcS2 and TcSe2 monolayers are calculated to be indirect semiconductors with band gaps of 1.91 and 1.69 eV, respectively. However, bilayer TcS2 exhibits direct bandgap character, and both TcS2 and TcSe2 monolayers can be tuned from semiconductor to metal under effective tensile/compressive strains. Calculations of visible light absorption indicate that 2D TcS2 and TcSe2 generally possess better capability of harvesting sunlight compared to single-layer MoS2 and ReSe2, implying their potential as excellent light-absorbers. Most interestingly, we have discovered that the TcSe2 monolayer is an excellent photocatalyst for splitting water into hydrogen due to the perfect fit of band edge positions with respect to the water reduction and oxidation potentials. Our predictions expand the two-dimensional (2D) family of TMDCs, and the remarkable electronic/optical properties of monolayer TcS2 and TcSe2 will place them among the most promising 2D TMDCs for renewable energy application in the future. PMID- 26859698 TI - Size-distribution of airborne polycyclic aromatic hydrocarbons and other organic source markers in the surroundings of a cement plant powered with alternative fuels. AB - The distributions of polycyclic aromatic hydrocarbons (PAHs) and molecular tracer organic compounds for biomass combustion, traffic emissions, soil dust, and secondary aerosol processing have been studied in three fractions of ambient air particulate matter (PM10, 2.5, and 1) collected in the vicinity of a cement plant. PAH concentrations were used to estimate the carcinogenic risks in humans. Combustion related compounds, including PAHs, and those from secondary aerosol processing, predominated in the finest (PM<1) fraction, while saccharides related to organic soil dust predominated in the coarse fraction (2.5= 30. Blood pressure (BP) values were measured at four time points (daytime, evening, nighttime, and morning). The prevalence of hypertension and BP values in the different groups were compared at four time points. Finally, the nighttime-to-daytime mean BP (MBP; RN/D) and morning-to-evening MBP (RM/E) ratios were calculated. RESULTS: The prevalence of hypertension in the control group, mild group, moderate group, and severe group were 22.32%, 34.65%, 39.04%, and 55.37%, respectively. AHI positively correlated with the prevalence of hypertension (r = .191, p < .001). The daytime, nighttime, evening, and morning MBP rose as AHI increased. The ratios of nighttime-to-daytime MBP (RN/D) and morning-to-evening MBP (RM/E) increase with the severity of the illness (F = 9.821 and 18.957; p < .001). The daytime BP correlates significantly with AHI and lowest oxygen saturation (LSaO2; systolic BP, r = .195 and -.206; diastolic BP, rs = .248 and -.251, p < .01). Daytime MBP increases gradually in small fluctuations concurrent with increases in AHI until 61-65. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: OSAHS is an independent risk factor for hypertension. Patients with OSAHS have a significant increase in nighttime and morning BP, which means they lose normal BP diurnal rhythm. Therefore, nurses should take necessary measures based on the clinical features of hypertension in patients with OSAHS to minimize the risk of cardiocerebral vascular incidents. PMID- 26859737 TI - Taiwanese Version of the Work-Related Quality of Life Scale for Nurses: Translation and Validation. AB - BACKGROUND: The shortage of professional nurses is a global issue of critical importance. Improving the retention and recruitment of nurses is necessary to reduce this shortage. The ability to measure the quality of work life (QWL) of nurses is important to understand the current QWL status among nurses and to develop appropriate improvement strategies. The two instruments that are currently used in Taiwan both require excessive amounts of time to complete. Furthermore, the results that these two instruments generate are not easily interdisciplinary and international comparisons. PURPOSE: The aims of this study were to translate into Chinese the English version of the Work-Related Quality of Life Scale (WRQoL) that was developed by Van Laar, Edwards, and Easton (2007) and then to determine the reliability and validity of this Chinese-version scale in terms of measuring the QWL of nurses in Taiwan. METHODS: The WRQoL was translated from English into Chinese using forward-translation with group discussions, back translation, and verification of conceptual equivalence. Concurrent validity, test-retest reliability, and internal consistency reliability were determined in two samples of nurses (n = 30 and n = 213 for Phases 1 and 2, respectively) from a medical center in Taiwan during September 2009. RESULTS: The 23-item Taiwanese version of the WRQoL showed satisfactory concurrent validity with a Taiwanese QWL scale (correlation = .75). The 3-week test-retest reliability was .89, and the Cronbach's alpha was .88, indicating high internal consistency reliability. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The Taiwanese version of the WRQoL is acceptable for measuring the QWL of nurses in Taiwan. Larger scale studies are recommended for confirmatory factor analysis. This tool may be used for human resources management and policy-making applications, providing the potential to help retain and recruit nurses in Taiwan. Furthermore, the Taiwanese-version scale may be used to compare work-related quality of life between Taiwanese nurses and their counterparts overseas. PMID- 26859738 TI - Methods to Estimate Acclimatization to Urban Heat Island Effects on Heat- and Cold-Related Mortality. AB - BACKGROUND: Investigators have examined whether heat mortality risk is increased in neighborhoods subject to the urban heat island (UHI) effect but have not identified degrees of difference in susceptibility to heat and cold between cool and hot areas, which we call acclimatization to the UHI. OBJECTIVES: We developed methods to examine and quantify the degree of acclimatization to heat- and cold related mortality in relation to UHI anomalies and applied these methods to London, UK. METHODS: Case-crossover analyses were undertaken on 1993-2006 mortality data from London UHI decile groups defined by anomalies from the London average of modeled air temperature at a 1-km grid resolution. We estimated how UHI anomalies modified excess mortality on cold and hot days for London overall and displaced a fixed-shape temperature-mortality function ("shifted spline" model). We also compared the observed associations with those expected under no or full acclimatization to the UHI. RESULTS: The relative risk of death on hot versus normal days differed very little across UHI decile groups. A 1 degrees C UHI anomaly multiplied the risk of heat death by 1.004 (95% CI: 0.950, 1.061) (interaction rate ratio) compared with the expected value of 1.070 (1.057, 1.082) if there were no acclimatization. The corresponding UHI interaction for cold was 1.020 (0.979, 1.063) versus 1.030 (1.026, 1.034) (actual versus expected under no acclimatization, respectively). Fitted splines for heat shifted little across UHI decile groups, again suggesting acclimatization. For cold, the splines shifted somewhat in the direction of no acclimatization, but did not exclude acclimatization. CONCLUSIONS: We have proposed two analytical methods for estimating the degree of acclimatization to the heat- and cold-related mortality burdens associated with UHIs. The results for London suggest relatively complete acclimatization to the UHI effect on summer heat-related mortality, but less clear evidence for cold-related mortality. CITATION: Milojevic A, Armstrong BG, Gasparrini A, Bohnenstengel SI, Barratt B, Wilkinson P. 2016. Methods to estimate acclimatization to urban heat island effects on heat- and cold-related mortality. Environ Health Perspect 124:1016-1022; http://dx.doi.org/10.1289/ehp.1510109. PMID- 26859739 TI - The Efficacy of Single-Agent Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy in Biologically Selected Patients with Non-Small-Cell Lung Cancer: A Meta-Analysis of 19 Randomized Controlled Trials. AB - OBJECTIVE: To determine the efficacy of first-generation single-agent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy in advanced non-small-cell lung cancer patients with known EGFR mutation status, we undertook this pooled analysis. METHOD: We searched for randomized controlled trials (RCTs) in Medline, Embase, the Cochrane Controlled Trials Register, the Science Citation Index, and the American Society of Clinical Oncology annual meetings. RESULTS: Out of 2,129 retrieved articles, 19 RCTs enrolling 2,016 patients with wild-type EGFR tumors and 1,034 patients with mutant EGFR tumors were identified. For these EGFR mutant patients, single-agent EGFR-TKI therapy improved progression-free survival (PFS) over chemotherapy: the summary hazard ratios (HRs) were 0.41 (p < 0.001) for the first-line setting and 0.46 (p = 0.02) for the second-/third-line setting. For those EGFR wild-type patients, single-agent EGFR-TKI therapy did not do as well as chemotherapy in the first-line setting (HR = 1.65, p = 0.03) and in the second-/third-line setting (HR = 1.27, p = 0.006). No statistically significant difference was observed in terms of overall survival (OS). Using platinum-based doublet chemotherapy as a common comparator, indirect comparison showed the superior efficacy of single-agent EGFR-TKI therapy over EGFR-TKIs added to chemotherapy in PFS [HR = 1.35 (1.03, 1.77), p = 0.03]. Additionally, a marginal trend towards the same direction was found in the OS analysis [HR = 1.16 (0.99, 1.35), p = 0.06]. Interestingly, for those EGFR wild-type tumors, single agent EGFR-TKI therapy was inferior to EGFR-TKIs added to chemotherapy in PFS [HR = 0.38 (0.33, 0.44), p < 0.001] and OS [HR = 0.83 (0.71, 0.97), p = 0.02]. CONCLUSIONS: For these EGFR mutant patients, single-agent EGFR-TKI therapy prolonged PFS over chemotherapy. However, single-agent EGFR-TKI therapy was inferior to chemotherapy in PFS for those EGFR wild-type patients. Single-agent EGFR-TKI therapy could improve PFS over the combination of EGFR-TKIs and chemotherapy in these EGFR mutant patients. However, EGFR-TKIs combined with chemotherapy could provide additive PFS and OS benefit over single-agent EGFR-TKI therapy in those EGFR wild-type patients. PMID- 26859740 TI - Correction of Midface Depression Using an Inverted m-shaped Expanded Polytetrafluoroethylene Implant Improves Gingival Exposure. AB - BACKGROUND: Current approaches for the treatment of gingival exposure are often time- and cost-consuming and/or rather invasive. We previously observed a strong correlation between the presence of gingival excess and midfacial depression and here propose an easy 1-step correction technique as a new strategy to improve gingival exposure. METHOD: From February 2004 to December 2012, 42 patients with gingival exposure associated with different degrees of midfacial depression, defined by Frankfort horizontal plane-labrale superius-subspinale angle and sella nasion-A point angle, were treated by implantation of an inverted m-shaped expanded polytetrafluoroethylene at the base of the piriform aperture in a subperiosteal location. Patient pictures were taken preoperatively and postoperatively to assess gingival exposure at rest and fullest smile, as well as measurements of upper lip length, nasolabial angle, and facial convexity angle. A postoperative patient satisfaction survey was performed. RESULTS: The average maximum gingival exposure was 5.52 +/- 1.64 mm preoperatively and significantly decreased to 1.79 +/- 0.67 mm at 6 months after surgery (P < 0.05) along with a significantly improved nasolabial angle from initially 85.3 degrees +/- 6.21 degrees to 95.2 degrees +/- 7.1 degrees (P < 0.05). The majority of patients (90.5%) rated their postoperative outcome as highly improved and improved. Temporary discomfort involving upper lip numbness, foreign body sensation, and stiff smiling expression was complained at 1 month postoperatively and gradually returned to normal after 3 months. No late recurrence or other complications were seen in any of the patients. CONCLUSIONS: For cases involving midface depression, the present technique provides an effective and permanent treatment strategy to improve excessive gingival exposure. This single-step approach is a safe and technically easy therapeutic option which is associated with high patient acceptance. PMID- 26859741 TI - Effect of Lens Care Systems on Silicone Hydrogel Contact Lens Hydrophobicity. AB - PURPOSE: To analyze changes in wettability of hydrogel and silicone hydrogel contact lenses (CLs) when preserved in different lens care systems. METHODS: In this research, four silicone hydrogel CLs (senofilcon A, balafilcon A, comfilcon A, and lotrafilcon B) and one conventional CL (etafilcon A) and appropriate lens care solutions (ReNu MultiPlus, Biotrue, OPTI-FREE PureMoist, and AOSept Plus) were used. Lenses were immersed in each lens care system for 12 hr and then CL hydrophobicity was determined through water contact angle (CA) measurements using the OCA 20 instrument (DataPhysics). RESULTS: Mean CA values obtained when CLs were removed from blisters (baseline value) were lower for etafilcon A (49.6 degrees +/-3.0 degrees ) and comfilcon A (48.0 degrees +/-2.8 degrees ) and higher for senofilcon A (78.9 degrees +/-2.5 degrees ), lotrafilcon B (82.6 degrees +/-1.7 degrees ), and balafilcon A (91.5 degrees +/-0.7 degrees ). Depending on CL and lens care combination, it was detected a statistically significant reduction by 70% of the 20 combinations studied and any significant increase in the CA. When compared to baseline values, CA varied between etafilcon A: 2 degrees and 11 degrees , comfilcon A: 1 degrees and 7 degrees , senofilcon A: 2 degrees and 28 degrees , lotrafilcon B: 14 degrees and 31 degrees , and balafilcon A: 18 degrees and 29 degrees . Comfilcon A was the most stable lens material presenting only one significant decrease in CA. CONCLUSIONS: This study reveals the existence of interactions between CL material and lens solutions that can play an important role in CL surface wettability. The major changes were obtained in lenses with higher baseline CA, which showed significant changes with each of the solutions. These differences can be positive, because in almost all of the combinations, the lenses became more wettable. PMID- 26859743 TI - Iodine-catalyzed synthesis of dibenzo[b,h][1,6]naphthyridine-11-carboxamides via a domino reaction involving double elimination of hydrogen bromide. AB - An iodine-catalyzed reaction of 2-aminobenzamides and mucobromic acid was described and utilized to synthesize a variety of 6-oxo-5,6 dihydrodibenzo[b,h][1,6]naphthyridine-11-carboxamide derivatives in refluxing THF. As the two bromine atoms in mucobromic acid were found missing in the dibenzonaphthyridine products, a domino-type reaction mechanism involving a double elimination of hydrogen bromide was proposed. PMID- 26859742 TI - Bacterial Bioburden Decrease in Orthokeratology Lens Storage Cases After Forewarning: Assessment by the DNA Dot Hybridization Assay. AB - BACKGROUND: The aim of this study was to measure the changes in the bacterial bioburden in orthokeratology (OK) lens storage cases using the DNA dot hybridization assay (DHA) after forewarning patients about their bacterial contamination severity. METHODS: Thirty-one OK lens wearers were prospectively enrolled in this study. Dot hybridization assay was used for serial measurements of bacterial bioburden in OK storage cases after lenses had been soaked for approximately 6 hr. After the first assessment, the lens wearers were informed of the extent of case contamination and the possible risk of microbial keratitis (MK), and best practices for lens care and lens case hygiene were reviewed and reinforced. A second assessment by the same DHA method was performed after approximately 6 months. RESULTS: Two universal bacterial probes confirmed a significant decrease in bacterial bioburden at the second assessment (P<0.01 and P<0.001). Genus-specific probes showed significant reductions in Acinetobacter and Klebsiella (P=0.02 and P=0.01), but not in Pseudomonas (P=0.42). CONCLUSIONS: Making OK lens wearers aware of the bacterial bioburden in their lens cases resulted in improved quality of case care and reduced bioburden. Our results suggest that a strategy of bioburden assessment with forewarning could be a useful method to decrease the incidence of OK-related MK. PMID- 26859744 TI - Influence of Selective Biochemical and Morphological Agents on Natural History of Aneurysm of Abdominal Aorta Development. AB - BACKGROUND The development of abdominal aortic aneurysm (AAA) is probably influenced by many factors. The role of some of these factors, such as intraluminal thrombus (ILT) or cystatin C serum levels, remains controversial. Proving their influence could have therapeutic implications for some patients with AAA. Associations between the rate of increase in diameter of an aneurysm and ILT, as well as other factors, including biochemical factors (C-Reactive Protein - CRP, cystatin C), age, sex, and comorbidities, could predict disease progression in individual patients. MATERIAL AND METHODS Seventy patients with small AAA were included into the study. The patients were followed using ultrasound and CT imaging. We evaluated aneurysm dimensions and aneurysm wall thickness, as well as ILT and its dimensions, aneurysm wall morphology, CRP, and cystatin C. RESULTS We observed significant growth of AAA and thinning of aneurysmal wall. Aneurysms over 4 cm grew significantly faster in the second year of observation. ILT grew together with AAA size. Age, sex, smoking, dyslipidemias, or controlled arterial hypertension had no influence on aneurysm progression rate. Changes in serum of CRP concentration did not reach statistical significance, but cystatin C levels did. CONCLUSIONS Presence and size of ILT, wall thickness, and cystatin C levels may be considered in prediction of AAA progression. ILT might exert a protective influence on the risk of aneurysm rupture. However, larger aneurysms containing larger thrombi grow faster and their walls undergo more rapid degradation, which in turn increases the risk of rupture. This matter requires further studies. PMID- 26859745 TI - Changes in the Proteome of Langat-Infected Ixodes scapularis ISE6 Cells: Metabolic Pathways Associated with Flavivirus Infection. AB - BACKGROUND: Ticks (Family Ixodidae) transmit a variety of disease causing agents to humans and animals. The tick-borne flaviviruses (TBFs; family Flaviviridae) are a complex of viruses, many of which cause encephalitis and hemorrhagic fever, and represent global threats to human health and biosecurity. Pathogenesis has been well studied in human and animal disease models. Equivalent analyses of tick flavivirus interactions are limited and represent an area of study that could reveal novel approaches for TBF control. METHODOLOGY/PRINCIPAL FINDINGS: High resolution LC-MS/MS was used to analyze the proteome of Ixodes scapularis (Lyme disease tick) embryonic ISE6 cells following infection with Langat virus (LGTV) and identify proteins associated with viral infection and replication. Maximal LGTV infection of cells and determination of peak release of infectious virus, was observed at 36 hours post infection (hpi). Proteins were extracted from ISE6 cells treated with LGTV and non-infectious (UV inactivated) LGTV at 36 hpi and analyzed by mass spectrometry. The Omics Discovery Pipeline (ODP) identified thousands of MS peaks. Protein homology searches against the I. scapularis IscaW1 genome assembly identified a total of 486 proteins that were subsequently assigned to putative functional pathways using searches against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. 266 proteins were differentially expressed following LGTV infection relative to non-infected (mock) cells. Of these, 68 proteins exhibited increased expression and 198 proteins had decreased expression. The majority of the former were classified in the KEGG pathways: "translation", "amino acid metabolism", and "protein folding/sorting/degradation". Finally, Trichostatin A and Oligomycin A increased and decreased LGTV replication in vitro in ISE6 cells, respectively. CONCLUSIONS/SIGNIFICANCE: Proteomic analyses revealed ISE6 proteins that were differentially expressed at the peak of LGTV replication. Proteins with increased expression following infection were associated with cellular metabolic pathways and glutaminolysis. In vitro assays using small molecules implicate malate dehydrogenase (MDH2), the citrate cycle, cellular acetylation, and electron transport chain processes in viral replication. Proteins were identified that may be required for TBF infection of ISE6 cells. These proteins are candidates for functional studies and targets for the development of transmission-blocking vaccines and drugs. PMID- 26859746 TI - The Metastatic Potential and Chemoresistance of Human Pancreatic Cancer Stem Cells. AB - Cancer stem cells (CSCs) typically have the capacity to evade chemotherapy and may be the principal source of metastases. CSCs for human pancreatic ductal carcinoma (PDAC) have been identified, but neither the metastatic potential nor the chemoresistance of these cells has been adequately evaluated. We have addressed these issues by examining side-population (SP) cells isolated from the Panc-1 and BxPC3 lines of human PDAC cells, the oncogenotypes of which differ. SP cells could be isolated from monolayers of Panc-1, but only from spheroids of BxPC3. Using orthotopic xenografts into the severely immunocompromised NSG mouse, we found that SP cells isolated from both cell lines produced tumors that were highly metastatic, in contrast to previous experience with PDAC cell lines. SP cells derived from both cell lines expressed the ABCG2 transporter, which was demonstrably responsible for the SP phenotype. SP cells gave rise to non-SP (NSP) cells in vitro and in vivo, a transition that was apparently due to posttranslational inhibition of the ABCG2 transporter. Twenty-two other lines of PDAC cells also expressed ABCG2. The sensitivity of PDAC SP cells to the vinca alkaloid vincristine could be greatly increased by verapamil, a general inhibitor of transporters. In contrast, verapamil had no effect on the killing of PDAC cells by gemcitabine, the current first-line therapeutic for PDAC. We conclude that the isolation of SP cells can be a convenient and effective tool for the study of PDAC CSCs; that CSCs may be the principal progenitors of metastasis by human PDAC; that the ABCG2 transporter is responsible for the SP phenotype in human PDAC cells, and may be a ubiquitous source of drug-resistance in PDAC, but does not confer resistance to gemcitabine; and that inhibition of ABCG2 might offer a useful adjunct in a therapeutic attack on the CSCs of PDAC. PMID- 26859747 TI - The Daiokanzoto (TJ-84) Kampo Formulation Reduces Virulence Factor Gene Expression in Porphyromonas gingivalis and Possesses Anti-Inflammatory and Anti Protease Activities. AB - Kampo formulations used in Japan to treat a wide variety of diseases and to promote health are composed of mixtures of crude extracts from the roots, bark, leaves, and rhizomes of a number of herbs. The present study was aimed at identifying the beneficial biological properties of Daiokanzoto (TJ-84), a Kampo formulation composed of crude extracts of Rhubarb rhizomes and Glycyrrhiza roots, with a view to using it as a potential treatment for periodontal disease. Daiokanzoto dose-dependently inhibited the expression of major Porphyromonas gingivalis virulence factors involved in host colonization and tissue destruction. More specifically, Daiokanzoto reduced the expression of the fimA, hagA, rgpA, and rgpB genes, as determined by quantitative real-time PCR. The U937 3xkappaB-LUC monocyte cell line transfected with a luciferase reporter gene was used to evaluate the anti-inflammatory properties of Daiokanzoto. Daiokanzoto attenuated the P. gingivalis-mediated activation of the NF-kappaB signaling pathway. It also reduced the secretion of pro-inflammatory cytokines (IL-6 and CXCL8) by lipopolysaccharide-stimulated oral epithelial cells and gingival fibroblasts. Lastly, Daiokanzoto, dose-dependently inhibited the catalytic activity of matrix metalloproteinases (-1 and -9). In conclusion, the present study provided evidence that Daiokanzoto shows potential for treating and/or preventing periodontal disease. The ability of this Kampo formulation to act on both bacterial pathogens and the host inflammatory response, the two etiological components of periodontal disease, is of high therapeutic interest. PMID- 26859748 TI - Influence of Temperature on Intra- and Interspecific Resource Utilization within a Community of Lepidopteran Maize Stemborers. AB - Competition or facilitation characterises intra- and interspecific interactions within communities of species that utilize the same resources. Temperature is an important factor influencing those interactions and eventual outcomes. The noctuid stemborers, Busseola fusca and Sesamia calamistis and the crambid Chilo partellus attack maize in sub-Saharan Africa. They often occur as a community of interacting species in the same field and plant at all elevations. The influence of temperature on the intra- and interspecific interactions among larvae of these species, was studied using potted maize plants exposed to varying temperatures in a greenhouse and artificial stems kept at different constant temperatures (15 degrees C, 20 degrees C, 25 degrees C and 30 degrees C) in an incubator. The experiments involved single- and multi-species infestation treatments. Survival and relative growth rates of each species were assessed. Both intra- and interspecific competitions were observed among all three species. Interspecific competition was stronger between the noctuids and the crambid than between the two noctuids. Temperature affected both survival and relative growth rates of the three species. Particularly at high temperatures, C. partellus was superior in interspecific interactions shown by higher larval survival and relative growth rates. In contrast, low temperatures favoured survival of B. fusca and S. calamistis but affected the relative growth rates of all three species. Survival and relative growth rates of B. fusca and S. calamistis in interspecific interactions did not differ significantly across temperatures. Temperature increase caused by future climate change is likely to confer an advantage on C. partellus over the noctuids in the utilization of resources (crops). PMID- 26859749 TI - Toll-Like Receptor 11 (TLR11) Interacts with Flagellin and Profilin through Disparate Mechanisms. AB - Toll-like receptors (TLRs) are innate immune receptors that sense a variety of pathogen-associated molecular patterns (PAMPs) by interacting with them and subsequently initiating signal transduction cascades that elicit immune responses. TLR11 has been shown to interact with two known protein PAMPs: Salmonella and E. coli flagellin FliC and Toxoplasma gondii profilin-like protein. Given the highly divergent biology of these pathogens recognized by TLR11, it is unclear whether common mechanisms are used to recognize these distinct protein PAMPs. Here we show that TLR11 interacts with these two PAMPs using different receptor domains. Furthermore, TLR11 binding to flagellin and profilin exhibits differential dependency on pH and receptor ectodomain cleavage. PMID- 26859752 TI - A qualitative exploration of supports and unmet needs of diverse young women with breast cancer. AB - BACKGROUND: Young women with breast cancer face different challenges than those faced by older women because of their age and life stage, yet few studies have focused on the different challenges faced by women from diverse populations. OBJECTIVE: To explore existing supports that are important during diagnosis and treatment and the unmet needs for information and support in young women with breast cancer. METHODS: We conducted 20 semistructured interviews in English with women aged 42 or younger who had been diagnosed with stage I-III invasive breast cancer within the previous 4 years. We recorded and transcribed the interviews and used collaborative group immersion/ crystallization to analyze data, identify emergent themes, and determine if there were differences by race/ethnicity. RESULTS: 20 participants, recruited from 9 US states and Canada, were interviewed, of whom 25% were Hispanic, 15% were black, 50% were white and non Hispanic, and 10% were another race/ethnicity. Faith and/or spirituality and family were reported as important sources of support by many of the participants. Most of them lamented the inadequacy of their connections with other young survivors and also of supports for their family. Some recommended that young patients be provided with more information about: treatment-related physical and emotional changes; fertility and menopause; relationships after cancer; navigating work challenges; and transitioning into survivorship. None of these supports or recommendations was limited to a specific race/ethnicity or geographic region. LIMITATIONS: Small sample size, exclusion of non-English speakers. Conclusions Key informant interviews of young breast cancer survivors identified similar needs for education and support across various races/ethnicities and geographies. CONCLUSIONS: Key informant interviews of young breast cancer survivors identified similar needs for education and support across various races/ethnicities and geographies. PMID- 26859750 TI - Effects of Oxygen Limitation on the Biosynthesis of Photo Pigments in the Red Microalgae Galdieria sulphuraria Strain 074G. AB - As a consequence of the inhibition of one of the steps in the biosynthesis of the photopigments chlorophyll and phycobilin, the red microalga Galdieria partita excretes coproporphyrinogen III in the medium when growing on glucose. No coproporphyrinogen III was found when the closely related red microalgae G. sulphuraria strain 074G was grown on glucose and excessive amounts of oxygen. When under the same conditions oxygen was limiting, coproporphyrinogen III was present in the medium. We conclude that not glucose but the amount of oxygen in the medium results in the accumulation of coproporphyrinogen III. This is explained by the inactivition of the oxygen-dependent coproporphyrinogen III oxidase that converts coproporhyrinogen III to protoporphyrinogen IX, one of the intermediate steps in the biosynthesis of chlorophyl and phycobilin. PMID- 26859751 TI - Hospital readmission following transplantation: identifying risk factors and designing preventive measures. AB - BACKGROUND: About 1 in 7 of all hospitalized patients is readmitted within 30 days of discharge. The cost of readmissions is significant, with Medicare readmissions alone costing the health care system an estimated $28 billion a year. OBJECTIVE: To identify the rates of and causes for readmission within 100 days of patients receiving a hematopoietic stem cell transplant. METHODS: We performed a retrospective review of 235 consecutive transplant recipients (autologous, n = 144; allogeneic, n = 91) to determine rates and causes for readmission within 100 days of patients receiving a transplant. Medical records and hospital readmissions were reviewed for each patient. RESULTS: 36 allogeneic patients accounted for 56 readmissions. 23 autologous patients accounted for 26 readmissions. Autologous transplant recipients were most commonly readmitted for the development of a fever (n = 15 patients) or cardiopulmonary issues (n = 4). The most prevalent reasons for readmission in the allogeneic recipients included a fever (n = 21) or the development or exacerbation of graft-versus-host disease (n = 5). The readmission length of stay was 6 days (median range, 1-91 days) for allogeneic patients and 4 days (median range, 1-22 days) for autologous patients. There was no difference in survival between the readmitted and the non-readmitted cohorts (?? = .55 for allogeneic patients; ?? = .24 for autologous patients). Although allogeneic graft recipients demonstrated a higher readmission rate (39.6%) compared with autologous recipients (16%), none of the variables examined, including age, gender, performance status, diagnosis, remission status at the time of transplant, comorbidities, type of preparative chemotherapy regimen or donor type, identified patients at increased risk for readmission. LIMITATIONS: Variations in clinical care, physician practices, and patient characteristics need to be considered when examining readmission rates. Most of the allogeneic patient population included unrelated donor recipients (65%) who received nonmyeloablative conditioning regimens (81% of allogeneic recipients). These features may not be characteristic of other centers. CONCLUSIONS: In these high-risk patients, readmissions following a transplant are common. Enhanced predischarge education by nurses and pharmacists, along with ongoing outpatient education and rigorous outpatient follow-up through phone calls or social media may decrease readmission rates. PMID- 26859753 TI - Effects of a self-care education program on quality of life of patients with gastric cancer after gastrectomy. AB - BACKGROUND: Gastrectomy affects different aspects of functionality and impacts on the quality of life (QoL) of patients with gastric cancer. The importance of appropriate assessment of QoL in cancer patients is well established, yet strategies that help improve this important patient outcome are relatively scarce. OBJECTIVE: To examine the effectiveness of a brief self-care education program to improve QoL of gastric cancer patients after gastrectomy. METHODS: Using a randomized controlled trial, 59 patients with gastric cancer and candidate for gastrectomy were randomly assigned either to an intervention group (n = 31) to participate in a brief self-care education program or to a usual-care group (n = 28). Data were collected on patient demographics, and QoL was measured by the QLQ-C30 and the QLQ-STO22 at baseline and 1 month after gastrectomy. RESULTS: There were no statistically significant between-group differences in any subscales of the QLQ-C30 and the QLQ-STO22. However, participants in the brief self-care education program showed significant improvements from baseline in the global health status-QoL scale (t = 2.243, ?? < .05), experience of pain (t = 2.508, ?? < .05), constipation (t = 2.773, ?? < .05), and the experience of dysphagia at the follow-up assessment. LIMITATIONS: This study is likely to be underpowered to show differences between the groups. CONCLUSION: A brief self care education program was not sufficient to significantly improve the quality of life patients with gastric cancer after gastrectomy. PMID- 26859754 TI - Correction: From the Ground Up: Global Nitrous Oxide Sources are Constrained by Stable Isotope Values. PMID- 26859756 TI - Ethical issues in neuroprosthetics. AB - OBJECTIVE: Neuroprosthetics are artificial devices or systems designed to generate, restore or modulate a range of neurally mediated functions. These include sensorimotor, visual, auditory, cognitive affective and volitional functions that have been impaired or lost from congenital anomalies, traumatic brain injury, infection, amputation or neurodevelopmental and neurodegenerative disorders. Cochlear implants, visual prosthetics, deep brain stimulation, brain computer interfaces, brain-to-brain interfaces and hippocampal prosthetics can bypass, replace or compensate for dysfunctional neural circuits, brain injury and limb loss. They can enable people with these conditions to gain or regain varying degrees of control of thought and behavior. These direct and indirect interventions in the brain raise general ethical questions about weighing the potential benefit of altering neural circuits against the potential harm from neurophysiological and psychological sequelae. Other ethical questions are more specific to the therapeutic goals of particular neuroprosthetics and the conditions for which they are indicated. These include informed consent, agency, autonomy (free will) and identity. APPROACH: This review is an analysis and discussion of these questions. It also includes consideration of social justice issues such as how to establish and implement fair selection criteria in providing access to neuroprosthetic research and balancing technological innovation with patients' best interests. MAIN RESULTS: Neuroprosthetics can restore or improve motor and mental functions in bypassing areas of injury or modulating dysregulation in neural circuits. As enabling devices that integrate with these circuits, neuroprosthetics can restore varying degrees of autonomous agency for people affected by neurological and psychiatric disorders. They can also re-establish the connectedness and continuity of the psychological properties they had before injury or disease onset and thereby re-establish their identity. Neuroprosthetics can maximize benefit and minimize harm for people affected by damaged or dysfunctional brains and improve the quality of their lives. SIGNIFICANCE: Provided that adequate protections are in place for research subjects and patients, the probable benefit of research into and therapeutic applications of neuroprosthetics outweighs the risk and therefore can be ethically justified. Depending on their neurogenerative potential, there may be an ethical obligation to conduct this research. Advances in neuroscience will generate new ethical and philosophical questions about people and their brains. These questions should shape the evolution and application of novel techniques to better understand and treat brain disorders. PMID- 26859755 TI - Tree Age Effects on Fine Root Biomass and Morphology over Chronosequences of Fagus sylvatica, Quercus robur and Alnus glutinosa Stands. AB - There are few data on fine root biomass and morphology change in relation to stand age. Based on chronosequences for beech (9-140 years old), oak (11-140 years) and alder (4-76 years old) we aimed to examine how stand age affects fine root biomass and morphology. Soil cores from depths of 0-15 cm and 16-30 cm were used for the study. In contrast to previously published studies that suggested that maximum fine root biomass is reached at the canopy closure stage of stand development, we found almost linear increases of fine root biomass over stand age within the chronosequences. We did not observe any fine root biomass peak in the canopy closure stage. However, we found statistically significant increases of mean fine root biomass for the average individual tree in each chronosequence. Mean fine root biomass (0-30 cm) differed significantly among tree species chronosequences studied and was 4.32 Mg ha(-1), 3.71 Mg ha(-1) and 1.53 Mg ha( 1), for beech, oak and alder stands, respectively. The highest fine root length, surface area, volume and number of fine root tips (0-30 cm soil depth), expressed on a stand area basis, occurred in beech stands, with medium values for oak stands and the lowest for alder stands. In the alder chronosequence all these values increased with stand age, in the beech chronosequence they decreased and in the oak chronosequence they increased until ca. 50 year old stands and then reached steady-state. Our study has proved statistically significant negative relationships between stand age and specific root length (SRL) in 0-30 cm soil depth for beech and oak chronosequences. Mean SRLs for each chronosequence were not significantly different among species for either soil depth studied. The results of this study indicate high fine root plasticity. Although only limited datasets are currently available, these data have provided valuable insight into fine root biomass and morphology of beech, oak and alder stands. PMID- 26859757 TI - Distributions of autofluorescence after compensation: Be panglossian, fret not. AB - In this technical note, I describe an in silico model of multiparameter fluorescence measurements that takes into account intrinsic cellular autofluorescence and stained dye fluorescence distributions, fluorescence spectrum spillovers, and photon counting statistics. Using this model, it is easy to manipulate spectral variables as well as error terms to understand the impact of each on the distributions of estimated cell-associated dyes (e.g., conjugated monoclonal antibodies in immunophenotyping). An application of this model was to understand the genesis of "unusual" autofluorescence distributions that occasionally happen in multi-color immunophenotyping. These unusual distributions show striking correlated patterns (diagonals) for graphs of certain pairs of parameters. Here I show that these arise from combinations of spillover-spreading from unviewed parameters. While disconcerting to researchers taught to look for diagonals in distributions as heralding improper compensation, these distributions are in fact appropriate. In general, one can ignore the characteristics of cell distributions within the same limits as background (e.g., as proscribed by a fluorescence-minus-one, or FMO, control), as there is essentially no information content in that region. Published 2016 International Society for Advancement of Cytometry. This article is a US Government work, and as such, is in the public domain in the USA. PMID- 26859758 TI - In utero exposure to second-hand smoke activates pro-asthmatic and oncogenic miRNAs in adult asthmatic mice. AB - Exposures to environmental pollutants contribute to dysregulated microRNA (miRNA) expression profiles, which have been implicated in various diseases. Previously, we reported aggravated asthmatic responses in ovalbumin (OVA)-challenged adult mice that had been exposed in utero to second-hand smoke (SHS). Whether in utero SHS exposure dysregulates miRNA expression patterns in the adult asthma model has not been investigated. Pregnant BALB/c mice were exposed (days 6-19 of pregnancy) to SHS (10 mg/m(3)) or HEPA-filtered air. All offspring were sensitized and challenged with OVA (19-23 weeks) before sacrifice. RNA samples extracted from lung homogenates, were subjected to RNA sequencing (RNA-seq). RNA-seq identified nine miRNAs that were most significantly up-regulated by in utero SHS exposure. Among these nine, miR-155-5p, miR-21-3p, and miR-18a-5p were also highly correlated with pro-asthmatic Th2 cytokine levels in bronchoalveolar lavage fluid. Further analysis indicated that these up-regulated miRNAs shared common chromosome locations, particularly Chr 11C, with pro-asthmatic genes. These three miRNAs have also been characterized as oncogenic miRNAs (oncomirs). We cross referenced miRNA-mRNA expression profiles and identified 16 tumor suppressor genes that were down-regulated in the in utero-exposed offspring and that are predicted targets of the up-regulated oncomirs. In conclusion, in utero SHS exposure activates pro-asthmatic genes and miRNAs, which colocalize at specific chromosome locations, in OVA-challenged adult mice. The oncogenic characteristics of the miRNAs and putative miRNA-mRNA regulatory networks suggest that the synergistic effect of in utero SHS exposure and certain adult irritants may promote an oncogenic milieu in mouse lungs via inhibition of miRNA-regulated tumor suppressor genes. PMID- 26859760 TI - Protein regulation of induced pluripotent stem cells by transplanting in a Huntington's animal model. AB - AIMS: The purpose of this study was to determine the functional recovery and protein regulation by transplanted induced pluripotent stem cells in a rat model of Huntington's disease (HD). METHODS: In a quinolinic acid-induced rat model of striatal degeneration, induced pluripotent stem cells were transplanted into the ipsilateral lateral ventricle 10 days after the quinolinic acid injection. At 8 weeks after transplantation, fluorodeoxyglucose-PET/CT scan and balance-beam test were performed to evaluate the functional recovery of experimental rats. In addition, immunofluorescence and protein array analysis were used to investigate the regulation of stimulated protein expression in the striatum. RESULTS: At 8 weeks after induced pluripotent stem cell transplantation, motor function was improved in comparison with the quinolinic acid-treated rats. High fluorodeoxyglucose accumulation in the injured striatum was also observed by PET/CT scans. In addition, immunofluorescence analysis demonstrated that implanted cells migrated from the lateral ventricle into the lesioned striatum and differentiated into striatal projection neurons. Array analysis showed a significant upregulation of GFR (Glial cell line-derived neurotrophic factor receptor) alpha-1, Adiponectin/Acrp30, basic-fibroblast growth factors, MIP-1 (Macrophage-inflammatory protein) alpha and leptin, as well as downregulation of cytokine-induced neutrophil chemoattractant-3 in striatum after transplantatation of induced pluripotent stem cells in comparison with the quinolinic acid -treated rats. CONCLUSIONS: The findings in this work indicate that transplantation of induced pluripotent stem cells is a promising therapeutic candidate for HD. PMID- 26859759 TI - Newcastle Disease Virus V Protein Targets Phosphorylated STAT1 to Block IFN-I Signaling. AB - Newcastle disease virus (NDV) V protein is considered as an effector for IFN antagonism, however, the mechanism remains unknown. In this study, the expression of STAT1 and phospho-STAT1 in cells infected with NDV or transfected with V protein-expressing plasmids were analyzed. Our results showed that NDV V protein targets phospho-STAT1 reduction in the cells depends on the stimulation of IFN alpha. In addition, a V-deficient genotype VII recombinant NDV strain rZJ1-VS was constructed using reverse genetic technique to confirm the results. The rZJ1-VS lost the ability to reduce phospho-STAT1 and induced higher expression of IFN responsive genes in infected cells. Furthermore, treatment with an ubiquitin E1 inhibitor PYR-41 demonstrated that phospho-STAT1 reduction was caused by degradation, but not de-phosphorylation. We conclude that NDV V protein targets phospho-STAT1 degradation to block IFN-alpha signaling, which adds novel knowledge to the strategies used by paramyxoviruses to evade IFN. PMID- 26859764 TI - First Identification of the Toxicity of Microcystins on Pancreatic Islet Function in Humans and the Involved Potential Biomarkers. AB - Microcystins (MCs) produced by cyanobacteria have been recognized as a major public health threat. However, the toxicity of MCs to humans is still largely unknown. In this study, we examined the changes in pancreatic islet function in fishers exposed to ambient levels of MCs at Lake Taihu and, using a mouse model, explored the molecular mechanisms involved in toxicity. MCs content in the serum of fishers tested positive, with a range from 0.10 to 0.64 MUg/L. Both lower blood insulin levels (2.26 +/- 0.96 MUIU/mL) and impaired fasting glucose were found in participants from the Meiliang Bay area in Lake Taihu, where MC-LR levels were substantially greater than the MC threshold established by WHO for drinking water. Animal experiments showed that glucose level increased by 27.9% in mice exposed to 5 MUg/kg bw and decreased by 41.5% in mice exposed to 20 MUg/kg bw. Blood insulin levels declined by 21.9% and 56.2% in mice exposed to 5 and 20 MUg/kg bw MC-LR, respectively, which was consistent with the results observed in fishers. Furthermore, the diabetes gene pdx1 and several other proteins (such as Ppp3ca, Ide, Marcks, Pgk1, Suclg1, Ndufs4) involved in insulin secretion were identified for the first time in mice following MC-LR exposure; these biomarkers were considered responsible for MC-LR induced islet dysfunction. This study suggests that subchronic exposure to environmental levels of MCs may increase the risk of the occurrence of diabetes in humans. PMID- 26859761 TI - Transcriptomic Profile of Whole Blood Cells from Elderly Subjects Fed Probiotic Bacteria Lactobacillus rhamnosus GG ATCC 53103 (LGG) in a Phase I Open Label Study. AB - We examined gene expression of whole blood cells (WBC) from 11 healthy elderly volunteers participating on a Phase I open label study before and after oral treatment with Lactobacillus rhamnosus GG-ATCC 53103 (LGG)) using RNA-sequencing (RNA-Seq). Elderly patients (65-80 yrs) completed a clinical assessment for health status and had blood drawn for cellular RNA extraction at study admission (Baseline), after 28 days of daily LGG treatment (Day 28) and at the end of the study (Day 56) after LGG treatment had been suspended for 28 days. Treatment compliance was verified by measuring LGG-DNA copy levels detected in host fecal samples. Normalized gene expression levels in WBC RNA were analyzed using a paired design built within three analysis platforms (edgeR, DESeq2 and TSPM) commonly used for gene count data analysis. From the 25,990 transcripts detected, 95 differentially expressed genes (DEGs) were detected in common by all analysis platforms with a nominal significant difference in gene expression at Day 28 following LGG treatment (FDR<0.1; 77 decreased and 18 increased). With a more stringent significance threshold (FDR<0.05), only two genes (FCER2 and LY86), were down-regulated more than 1.5 fold and met the criteria for differential expression across two analysis platforms. The remaining 93 genes were only detected at this threshold level with DESeq2 platform. Data analysis for biological interpretation of DEGs with an absolute fold change of 1.5 revealed down-regulation of overlapping genes involved with Cellular movement, Cell to cell signaling interactions, Immune cell trafficking and Inflammatory response. These data provide evidence for LGG-induced transcriptional modulation in healthy elderly volunteers because pre-treatment transcription levels were restored at 28 days after LGG treatment was stopped. To gain insight into the signaling pathways affected in response to LGG treatment, DEG were mapped using biological pathways and genomic data mining packages to indicate significant biological relevance. TRIAL REGISTRATION: ClinicalTrials.gov NCT01274598. PMID- 26859765 TI - Can MLVA Differentiate among Endemic-Like MRSA Isolates with Identical Spa-Type in a Low-Prevalence Region? AB - The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Norway is low, but an endemic-like MRSA clone with Staphylococcal protein A (spa)-type t304 has been established especially in nursing homes in the Oslo region causing several large outbreaks. The challenge was that spa-typing and the gold standard Pulsed-Field Gel Electrophoresis (PFGE) were inadequate in discriminating isolates in outbreak investigations. Additional higher resolution genotyping methods were needed. The aims of this study were a) to evaluate whether Multiple Locus Variable number of tandem repeat Analysis (MLVA) could differentiate within the PFGE clusters between epidemiologically related and unrelated endemic-like ST8-MRSA-IV-t304-PVL-neg (MRSA-t304) isolates and b) investigate the evolution of the endemic-like MRSA-t304 clone over a 15-year time period. All MRSA-t304 isolates detected in the region from 1998 through April 2013 were included. In total, 194 of 197 isolates were available for PFGE and MLVA analyses. PFGE results on isolates from 1998-2010 have been published previously. Two PFGE clusters subdivided into eight MLVA types were detected. One major outbreak clone (PFGE cluster C2/ MLVA type MT5045) appeared from 2004 to 2011 causing long lasting and large outbreaks in seven nursing homes and one hospital. Five new MLVA types (N = 9 isolates) differing in only one VNTR compared to the outbreak clone C2/MT5045 were detected, but only one (C2/MT5044) was seen after 2011. We suggest that MLVA can replace PFGE analysis, but MLVA may not be the optimal method in this setting as it did not discriminate between all epidemiologically unrelated isolates. The results may indicate that all eight outbreaks in different locations within the PFGE C2 cluster may be branches of one large regional outbreak. The major outbreak strain C2/MT5045 may now, however, be under control, extinguished or has moved geographically. PMID- 26859763 TI - Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes. AB - Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human GXTs. Next, theses assays were tested on established diet-induced (obese C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio metabolic phenotype of various animal models or the effects of novel therapeutics. PMID- 26859766 TI - A Simple Test of Class-Level Genetic Association Can Reveal Novel Cardiometabolic Trait Loci. AB - BACKGROUND: Characterizing the genetic determinants of complex diseases can be further augmented by incorporating knowledge of underlying structure or classifications of the genome, such as newly developed mappings of protein-coding genes, epigenetic marks, enhancer elements and non-coding RNAs. METHODS: We apply a simple class-level testing framework, termed Genetic Class Association Testing (GenCAT), to identify protein-coding gene association with 14 cardiometabolic (CMD) related traits across 6 publicly available genome wide association (GWA) meta-analysis data resources. GenCAT uses SNP-level meta-analysis test statistics across all SNPs within a class of elements, as well as the size of the class and its unique correlation structure, to determine if the class is statistically meaningful. The novelty of findings is evaluated through investigation of regional signals. A subset of findings are validated using recently updated, larger meta-analysis resources. A simulation study is presented to characterize overall performance with respect to power, control of family-wise error and computational efficiency. All analysis is performed using the GenCAT package, R version 3.2.1. RESULTS: We demonstrate that class-level testing complements the common first stage minP approach that involves individual SNP-level testing followed by post-hoc ascribing of statistically significant SNPs to genes and loci. GenCAT suggests 54 protein-coding genes at 41 distinct loci for the 13 CMD traits investigated in the discovery analysis, that are beyond the discoveries of minP alone. An additional application to biological pathways demonstrates flexibility in defining genetic classes. CONCLUSIONS: We conclude that it would be prudent to include class-level testing as standard practice in GWA analysis. GenCAT, for example, can be used as a simple, complementary and efficient strategy for class-level testing that leverages existing data resources, requires only summary level data in the form of test statistics, and adds significant value with respect to its potential for identifying multiple novel and clinically relevant trait associations. PMID- 26859767 TI - Genome, transcriptome and methylome sequencing of a primitively eusocial wasp reveal a greatly reduced DNA methylation system in a social insect. AB - Comparative genomics of social insects has been intensely pursued in recent years with the goal of providing insights into the evolution of social behaviour and its underlying genomic and epigenomic basis. However, the comparative approach has been hampered by a paucity of data on some of the most informative social forms (e.g. incipiently and primitively social) and taxa (especially members of the wasp family Vespidae) for studying social evolution. Here, we provide a draft genome of the primitively eusocial model insect Polistes dominula, accompanied by analysis of caste-related transcriptome and methylome sequence data for adult queens and workers. Polistes dominula possesses a fairly typical hymenopteran genome, but shows very low genomewide GC content and some evidence of reduced genome size. We found numerous caste-related differences in gene expression, with evidence that both conserved and novel genes are related to caste differences. Most strikingly, these -omics data reveal a major reduction in one of the major epigenetic mechanisms that has been previously suggested to be important for caste differences in social insects: DNA methylation. Along with a conspicuous loss of a key gene associated with environmentally responsive DNA methylation (the de novo DNA methyltransferase Dnmt3), these wasps have greatly reduced genomewide methylation to almost zero. In addition to providing a valuable resource for comparative analysis of social insect evolution, our integrative omics data for this important behavioural and evolutionary model system call into question the general importance of DNA methylation in caste differences and evolution in social insects. PMID- 26859768 TI - Integration of Intention and Outcome for Moral Judgment in Frontotemporal Dementia: Brain Structural Signatures. AB - BACKGROUND: Moral judgment has been proposed to rely on a distributed brain network. This function is impaired in behavioral variant frontotemporal dementia (bvFTD), a condition involving damage to some regions of this network. However, no studies have investigated moral judgment in bvFTD via structural neuroimaging. METHODS: We compared the performance of 21 bvFTD patients and 19 controls on a moral judgment task involving scenarios that discriminate between the contributions of intentions and outcomes. Voxel-based morphometry was used to assess (a) the atrophy pattern in bvFTD patients, (b) associations between gray matter (GM) volume and moral judgments, and (c) structural differences between bvFTD subgroups (patients with relatively preserved moral judgment and patients with severer moral judgment impairments). RESULTS: Patients judged attempted harm as more permissible and accidental harm as less permissible than controls. The groups' performance on accidental harm was associated with GM volume in the precuneus. In controls, it was al- so associated with the ventromedial prefrontal cortex (VMPFC). Also, both groups' performance on attempted harm was associated with GM volume in the temporoparietal junction. Patients exhibiting worse performance displayed smaller GM volumes in the precuneus and temporal pole. CONCLUSIONS: Results suggest that moral judgment abnormalities in bvFTD are associated with impaired integration of intentions and outcomes, which depends on an extended brain network. In bvFTD, moral judgment seems to critically depend on areas beyond the VMPFC. PMID- 26859769 TI - Protistan community analysis: key findings of a large-scale molecular sampling. AB - Protists are perhaps the most lineage-rich of microbial lifeforms, but remain largely unknown. High-throughput sequencing technologies provide opportunities to screen whole habitats in depth and enable detailed comparisons of different habitats to measure, compare and map protistan diversity. Such comparisons are often limited by low sample numbers within single studies and a lack of standardisation between studies. Here, we analysed 232 samples from 10 sampling campaigns using a standardised PCR protocol and bioinformatics pipeline. We show that protistan community patterns are highly consistent within habitat types and geographic regions, provided that sample processing is standardised. Community profiles are only weakly affected by fluctuations of the abundances of the most abundant taxa and, therefore, provide a sound basis for habitat comparison beyond random short-term fluctuations in the community composition. Further, we provide evidence that distribution patterns are not solely resulting from random processes. Distinct habitat types and distinct taxonomic groups are dominated by taxa with distinct distribution patterns that reflect their ecology with respect to dispersal and habitat colonisation. However, there is no systematic shift of the distribution pattern with taxon abundance. PMID- 26859770 TI - Deciphering bifidobacterial-mediated metabolic interactions and their impact on gut microbiota by a multi-omics approach. AB - The intricacies of cooperation and competition between microorganisms are poorly investigated for particular components of the gut microbiota. In order to obtain insights into the manner by which different bifidobacterial species coexist in the mammalian gut, we investigated possible interactions between four human gut commensals, Bifidobacterium bifidum PRL2010, Bifidobacterium adolescentis 22L, Bifidobacterium breve 12L and Bifidobacterium longum subsp. infantis ATCC15697, in the intestine of conventional mice. The generated information revealed various ecological/metabolic strategies, including glycan-harvesting, glycan-breakdown and cross-feeding behavior, adopted by bifidobacteria in the highly competitive environment of the mammalian intestine. Introduction of two or multiple bifidobacterial strains caused a clear shift in the microbiota composition of the murine cecum. Whole-genome transcription profiling coupled with metagenomic analyses of single, dual or multiple associations of bifidobacterial strains revealed an expansion of the murine gut glycobiome toward enzymatic degradation of plant-derived carbohydrates, such as xylan, arabinoxylan, starch and host derived glycan substrates. Furthermore, these bifidobacterial communities evoked major changes in the metabolomic profile of the microbiota as observed by shifts in short chain fatty acid production and carbohydrate availability in the murine cecum. Overall, these data support an ecological role of bifidobacteria acting directly or through cross-feeding activities in shaping the gut murine microbiome to instigate an enrichment of saccharolytic microbiota. PMID- 26859771 TI - The energetics of anabolism in natural settings. AB - The environmental conditions that describe an ecosystem define the amount of energy available to the resident organisms and the amount of energy required to build biomass. Here, we quantify the amount of energy required to make biomass as a function of temperature, pressure, redox state, the sources of C, N and S, cell mass and the time that an organism requires to double or replace its biomass. Specifically, these energetics are calculated from 0 to 125 degrees C, 0.1 to 500 MPa and -0.38 to +0.86 V using CO2, acetate or CH4 for C, NO3(-) or NH4(+) for N and SO4(2-) or HS(-) for S. The amounts of energy associated with synthesizing the biomolecules that make up a cell, which varies over 39 kJ (g cell)(-1), are then used to compute energy-based yield coefficients for a vast range of environmental conditions. Taken together, environmental variables and the range of cell sizes leads to a ~4 orders of magnitude difference between the number of microbial cells that can be made from a Joule of Gibbs energy under the most (5.06 * 10(11) cells J(-1)) and least (5.21 * 10(7) cells J(-1)) ideal conditions. When doubling/replacement time is taken into account, the range of anabolism energies can expand even further. PMID- 26859772 TI - High-resolution phylogenetic microbial community profiling. AB - Over the past decade, high-throughput short-read 16S rRNA gene amplicon sequencing has eclipsed clone-dependent long-read Sanger sequencing for microbial community profiling. The transition to new technologies has provided more quantitative information at the expense of taxonomic resolution with implications for inferring metabolic traits in various ecosystems. We applied single-molecule real-time sequencing for microbial community profiling, generating full-length 16S rRNA gene sequences at high throughput, which we propose to name PhyloTags. We benchmarked and validated this approach using a defined microbial community. When further applied to samples from the water column of meromictic Sakinaw Lake, we show that while community structures at the phylum level are comparable between PhyloTags and Illumina V4 16S rRNA gene sequences (iTags), variance increases with community complexity at greater water depths. PhyloTags moreover allowed less ambiguous classification. Last, a platform-independent comparison of PhyloTags and in silico generated partial 16S rRNA gene sequences demonstrated significant differences in community structure and phylogenetic resolution across multiple taxonomic levels, including a severe underestimation in the abundance of specific microbial genera involved in nitrogen and methane cycling across the Lake's water column. Thus, PhyloTags provide a reliable adjunct or alternative to cost-effective iTags, enabling more accurate phylogenetic resolution of microbial communities and predictions on their metabolic potential. PMID- 26859773 TI - Multi-omics analysis of niche specificity provides new insights into ecological adaptation in bacteria. AB - Different lifestyles, ranging from a saprophyte to a pathogen, have been reported in bacteria of one species. Here, we performed genome-wide survey of the ecological adaptation in four Burkholderia seminalis strains, distinguished by their origin as part of the saprophytic microbial community of soil or water but also including human and plant pathogens. The results indicated that each strain is separated from the others by increased fitness in medium simulating its original niche corresponding to the difference between strains in metabolic capacities. Furthermore, strain-specific metabolism and niche survival was generally linked with genomic variants and niche-dependent differential expression of the corresponding genes. In particular, the importance of iron, trehalose and d-arabitol utilization was highlighted by the involvement of DNA methylation and horizontal gene transfer in niche-adapted regulation of the corresponding operons based on the integrated analysis of our multi-omics data. Overall, our results provided insights of niche-specific adaptation in bacteria. PMID- 26859775 TI - Gender Differences in Verbal and Visuospatial Working Memory Performance and Networks. AB - BACKGROUND: Working memory (WM) has been a matter of intensive basic and clinical research for some decades now. The investigation of WM function and dysfunction may facilitate the understanding of both physiological and pathological processes in the human brain. Though WM paradigms are widely used in neuroscientific and psychiatric research, conclusive knowledge about potential moderating variables such as gender is still missing. METHODS: We used functional magnetic resonance imaging to investigate the effects of gender on verbal and visuospatial WM maintenance tasks in a large and homogeneous sample of young healthy subjects. RESULTS: We found significant gender effects on both the behavioral and neurofunctional level. Females exhibited disadvantages with a small effect size in both WM domains accompanied by stronger activations in a set of brain regions (including bilateral substantia nigra/ventral tegmental area and right Broca's area) independent of WM modality. As load and task difficulty effects have been shown for some of these regions, the stronger activations may reflect a slightly lower capacity of both WM domains in females. Males showed stronger bilateral intraparietal activations next to the precuneus which were specific for the visuospatial WM task. Activity in this specific region may be associated with visuospatial short-term memory capacity. CONCLUSION: These findings provide evidence for a slightly lower capacity in both WM modalities in females. PMID- 26859774 TI - Psychometric Properties of Prodromal Questionnaire-Brief Version among Chinese Help-Seeking Individuals. AB - Prodromal Questionnaire (PQ) and Structured Interview for Prodromal Syndromes (SIPS) have been used as a two-stage process for identifying subjects at clinical high risk (CHR) of psychosis. The Prodromal Questionnaire-Brief version (PQ-B) contains 21 items derived from the PQ. The present study aimed to examine the psychometric properties of PQ-B in a Chinese help-seeking outpatient sample and to explore which items can better predict CHR diagnosis by SIPS and future transition to psychosis. In our preliminary epidemiological study, 1461 patients from a pool of 2101 individuals (15-45 years of age) completed the two-stage process. In the present study, 239 (20%) people were randomly selected among the sample who met the initial PQ-B screening criteria but had no positive diagnosis on SIPS, as well as 72 individuals with negative results on both PQ-B and SIPS, 89 prodromal and 105 psychotic subjects, yielding a total of 505 participants. The internal consistency coefficient for the PQ-B was good, with a Cronbach's alpha of 0.897. The concordant validity of PQ-B with SIPS dichotomized diagnosis of prodrome/psychosis versus no psychosis was 0.54. To ensure 80% or a higher sensitivity and a certain specificity, 7 and 24 were respectively set as the cutoff points for the PQ-B total score and distress score for Chinese help seeking outpatients. A logistic regression model based on six PQ-B items could allow predicting the psychotic diagnosis on SIPS, with an accuracy of 65.8%. Prodromal individuals who scored higher on the 12th item of PQ-B (Do you worry at times that something may be wrong with your mind?) were less likely to convert to psychosis. PQ-B is a useful instrument for screening CHR subjects, but the cutoff score may be higher than that recommended by the author scores for help-seeking individuals in outpatient clinics. Some specific PQ-B items may have significant predictive power on dichotomized SIPS diagnoses and deserve special attention from researchers in future studies. PMID- 26859776 TI - Bioactive Iridoid Glycosides from the Whole Plants of Rehmannia chingii. AB - Nine new iridoid glycosides, rehmachingiiosides A-I (1-9), together with 16 known analogues, were isolated from the whole plants of Rehmannia chingii. The structures of compounds 1-9 were elucidated on the basis of spectroscopic data analysis and from chemical evidence. Furthermore, in two vitro assays, compounds 5 and 10 showed an inhibitory effect on LPS-induced NO production with IC50 values of 2.5 and 7.3 MUM, and compounds 4, 6, and 10-12 (when evaluated at 10 MUM) exhibited evidence of hepatoprotective effects against APAP-induced HepG2 cell damage. PMID- 26859777 TI - Hydrophobic Organic Hole Transporters for Improved Moisture Resistance in Metal Halide Perovskite Solar Cells. AB - Solar cells based on organic-inorganic perovskite semiconductor materials have recently made rapid improvements in performance, with the best cells performing at over 20% efficiency. With such rapid progress, questions such as cost and solar cell stability are becoming increasingly important to address if this new technology is to reach commercial deployment. The moisture sensitivity of commonly used organic-inorganic metal halide perovskites has especially raised concerns. Here, we demonstrate that the hygroscopic lithium salt commonly used as a dopant for the hole transport material in perovskite solar cells makes the top layer of the devices hydrophilic and causes the solar cells to rapidly degrade in the presence of moisture. By using novel, low cost, and hydrophobic hole transporters in conjunction with a doping method incorporating a preoxidized salt of the respective hole transporters, we are able to prepare efficient perovskite solar cells with greatly enhanced water resistance. PMID- 26859778 TI - Gills as a glutathione-dependent metabolic barrier in Pacific oysters Crassostrea gigas: Absorption, metabolism and excretion of a model electrophile. AB - The mercapturic acid pathway (MAP) is a major phase II detoxification route, comprising the conjugation of electrophilic substances to glutathione (GSH) in a reaction catalyzed by glutathione S-transferase (GST) enzymes. In mammals, GSH conjugates are exported from cells, and the GSH-constituent amino acids (Glu/Gly) are subsequently removed by ectopeptidases. The resulting Cys-conjugates are reabsorbed and, finally, a mercapturic acid is generated through N-acetylation. This pathway, though very well characterized in mammals, is poorly studied in non mammalian biological models, such as bivalve mollusks, which are key organisms in aquatic ecosystems, aquaculture activities and environmental studies. In the present work, the compound 1-chloro-2,4-dinitrobenzene (CDNB) was used as a model electrophile to study the MAP in Pacific oysters Crassostrea gigas. Animals were exposed to 10MUM CDNB and MAP metabolites were followed over 24h in the seawater and in oyster tissues (gills, digestive gland and hemolymph). A rapid decay was detected for CDNB in the seawater (half-life 1.7h), and MAP metabolites peaked in oyster tissues as soon as 15min for the GSH-conjugate, 1h for the Cys-conjugate, and 4h for the final metabolite (mercapturic acid). Biokinetic modeling of the MAP supports the fast CDNB uptake and metabolism, and indicated that while gills are a key organ for absorption, initial biotransformation, and likely metabolite excretion, hemolymph is a possible milieu for metabolite transport along different tissues. CDNB-induced GSH depletion (4h) was followed by increased GST activity (24h) in the gills, but not in the digestive gland. Furthermore, the transcript levels of glutamate-cysteine ligase, coding for the rate limiting enzyme in GSH synthesis, and two phase II biotransformation genes (GSTpi and GSTo), presented a fast (4h) and robust (~6-70 fold) increase in the gills. Waterborne exposure to electrophilic compounds affected gills, but not digestive gland, while intramuscular exposure was able to modulate biochemical parameters in both tissues. This study is the first evidence of a fully functional and interorgan MAP pathway in bivalves. Hemolymph was shown to be responsible for the metabolic interplay among tissues, and gills, acting as a powerful GSH-dependent metabolic barrier against waterborne electrophilic substances, possibly also participating in metabolite excretion into the sea water. Altogether, experimental and modeled data fully agree with the existence of a classical mechanism for phase II xenobiotic metabolism and excretion in bivalves. PMID- 26859780 TI - The expression and function of E3 ligase SIAH2 in acute T lymphoblastic leukemia. AB - INTRODUCTION: The seven in absentia homolog 2 (SIAH2) protein plays a significant role in human cancer by regulating hypoxia-inducible factor-a (HIF-1alpha); however, its role in T-cell acute lymphoblastic leukemia (T-ALL) is less clear. METHODS: Immunofluorescence evaluation of SIAH2 protein expression and location were conducted in Jurkat cell (a T-ALL cell line) as well as in bone marrow mononuclear cells (BMMNCs) from T-ALL and idiopathic thrombocytopenic purpura (ITP) patients. The expression of SIAH2 mRNA was also examined by quantitative real-time PCR (qRT-PCR) in these cells. Lentivirus-packed shRNA targeting on SIAH2 (Lv-shSIAH2) was used to knock down SIAH2 expression in Jurkat cells. Cell proliferation, apoptosis, invasion and protein levels were then determined by CCK 8 assay, annexin V-PI assay, transwell and Western blotting, respectively. RESULTS: The mRNA expression of SIAH2 in BMMNCs from primary T-ALL patients was significantly higher than cells from ITP patients (P=0.0312); There were significant positive associations between SIAH2 expression and the extramedullary infiltration (EMI) (P=0.0003), especially with the mediastinal lymph node metastasis (P=0.0168) and the pleural effusion (P=0.014). However, SIAH2 expression in T-ALL BMMNCs was not correlated with age, gender, white cell count or the clinical risk classification. SIAH2 knockdown by shRNA led to increased apoptosis and decreased proliferation, migration and invasion of Jurkat cells. Moreover, Prolyl Hydroxylase (PHD), P27 and Caspase3 were upregulated and HIF 1alpha, VEGF, VEGF Receptor 2, MMP-13, CyclinE1, C-myc and BCL2 were downregulated in SIAH2 knockdown Jurkat cells. CONCLUSIONS: Our results suggest that SIAH2 regulates multi processes in T-ALL and may be an attractive therapeutic target. PMID- 26859779 TI - Combined effects of drought and the fungicide tebuconazole on aquatic leaf litter decomposition. AB - Loss of biodiversity and altered ecosystem functioning are driven by the cumulative effects of multiple natural and anthropogenic stressors affecting both quantity and quality of water resources. Here we performed a 40-day laboratory microcosm experiment to assess the individual and combined effects of drought and the model fungicide tebuconazole (TBZ) on leaf litter decomposition (LLD), a fundamental biogeochemical process in freshwater ecosystems. Starting out from a worst-case scenario perspective, leaf-associated microbial communities were exposed to severe drought conditions (four 5-day drought periods alternated with 4-day immersion periods) and/or a chronic exposure to TBZ (nominal concentration of 20MUgL(-1)). We assessed the direct effects of drought and fungicide on the structure (biomass, diversity) and activity (extracellular enzymatic potential) of fungal and bacterial assemblages colonizing leaves. We also investigated indirect effects on the feeding rates of the amphipod Gammarus fossarum on leaves previously exposed to drought and/or TBZ contamination. Results indicate a stronger effect of drought stress than fungicide contamination under the experimental conditions applied. Indeed, the drought stress strongly impacted microbial community structure and activities, inhibiting the LLD process and leading to cascading effects on macroinvertebrate feeding. However, despite the lack of significant effect of TBZ applied alone, the effects of drought on microbial functions (i.e., decrease in LLD and in enzymatic activities) and on Gammarus feeding rates were more pronounced when drought and TBZ stresses were applied together. In a perspective of ecological risk assessment and ecosystem management for sustainability, these findings stress the need for deeper insight into how multiple stressors can affect the functioning of aquatic ecosystems and associated services. PMID- 26859781 TI - A potential role of the NOD genetic background in mouse peritoneal macrophages for the development of primary effusion lymphoma. AB - Severe immunodeficient mice have become invaluable tools in human stem cell and tumor research. In this study, we compared the phagocytic activity of peritoneal macrophages against primary effusion lymphoma (PEL) among Rag-2/Jak3 double deficient (Rag-2(-/-)Jak3(-/-)) mice with NOD and non-NOD (Balb/c and C57/BL6). We also evaluated lymphomatous effusion and infiltration in a PEL xenograft mouse model using these severe immunodeficient mice. In the phagocytic assay, peritoneal macrophages in the NOD background phagocytosed CFSE-labeled BCBL-1, a PEL cell line, less efficiently than those in the non-NOD background. BCBL-1 cells were successfully engrafted into both the NOD background and non-NOD background; however, the volume of ascites of the NOD background was significantly higher than that of the non-NOD background. Moreover, the organ invasion of PEL cells was suppressed in non-NOD background mice. Thus, the NOD genetic background is considered to contribute to more lymphomatous effusion and the infiltration of PEL cells than a non-NOD background. Our results showed that the NOD background allowed more lymphomatous effusion and infiltration than other backgrounds and peritoneal macrophages played a critical role in preventing the growth and infiltration of PEL cells. PMID- 26859782 TI - Comparison of vindesine and prednisone and cyclophosphamide, etoposide, vindesine, and prednisone as first-line treatment for adult Langerhans cell histiocytosis: A single-center retrospective study. AB - OBJECTIVE: We compared the efficacy and clinical outcomes of vindesine and prednisone (VP) and cyclophosphamide, etoposide, vindesine, and prednisone (CEVP) regimens as first-line treatment for multisystem (MS) or multifocal single system (SS-m) adult Langerhans cell histiocytosis (LCH). METHOD: Clinical features, treatment response, and survival of adults with Langerhans cell histiocytosis treated at our center from January 2001 to January 2015 were reviewed retrospectively. RESULTS: Forty-five adult MS or SS-m LCH patients were treated (N=31, CEVP group; N=14, VP group). Both treatment groups had similar gender distributions, patient ages, and extent of disease. The non-active disease rate for both groups was 70.0% and 64.3% (P=0.775), respectively. Median follow-up was 74.9 (range: 2.8-183.6) months and recurrence rates were 71.0% and 78.6% (P=0.593), respectively. The need for second-line therapy was 64.5% and 71.4% (P=0.649), respectively, and mortality rates were 9.7% and 15.4% (P=0.586), respectively. Neutropenia occurred in 48.4% of CEVP-treated patients and 7.1% of VP-treated patients (P=0.008). CONCLUSIONS: CEVP or VP regimens for the treatment of adult SS-m or MS LCH showed similar efficacies, and both regimens were associated with high disease recurrence and the need for second-line therapy. PMID- 26859783 TI - Lymphoma of the liver: Clinicopathological features of 19 patients. AB - BACKGROUND: Liver is an organ that could either be involved by widespread lymphoma or rarely as a primary site of lymphoma. Although secondary involvement of liver by lymphoma is relatively common, primary hepatic lymphoma (PHL) represents only about 0.016% of all cases of non-Hodgkin lymphoma. Understanding the clinicopathological features of hepatic lymphoma would direct appropriate treatment and patient management. METHODS: We did a retrospective cohort study of 19 patients with liver biopsy-proven lymphoma, either as part of a systemic lymphoma or as a primary lesion, who were evaluated and treated at Harbor-UCLA Medical Center between 2004 and 2014. RESULTS: The 19 cases were divided into two groups. Nine of them showing systemic involvement including not only liver but also spleen and/or lymph nodes were grouped together. The other 10 cases which showed confined liver lesions without involvement of other lymphoid structures were grouped in the PHL group. Clinical features of the two groups were compared. Our study demonstrated that PHL most commonly affected middle-aged individuals (median age: 50 years), with a male-to-female ratio of about 2.3 to 1. The most frequent presenting symptom was right upper quadrant pain. In contrast, the group with systemic lymphoma involving liver most commonly affected younger patients (median age: 40 years), with a male-to-female ratio of about 8 to 1, and with abdominal pain as well as fever/chills as the most common presenting symptoms. The tumor burden at the presentation as suggested by serum lactate dehydrogenase (LDH) level was statistically significantly lower in the PHL group compared to the systemic group in this study (p<0.05). Viral infections were found in both groups, and we did not observe a clear association of any particular viral infection with PHL. Diffuse large B-cell lymphoma was identified as the major type of primary hepatic lymphoma (8 of 10 cases). Finally, the prognosis in the PHL group demonstrated by the duration of follow-up (average follow up: 50 months) was statistically significantly better than that in the systemic group (average follow up: 5.5 months), p<0.01. CONCLUSION: Patients with PHL showed different clinicopathological features from those with widespread lymphoma involving liver. The outcome of the patients with PHL appeared much more favorable than that of the patients with liver involvement by systemic lymphoma in this study. PMID- 26859784 TI - A Case Control Study of Diabetes During Pregnancy and Low Milk Supply. AB - OBJECTIVE: The objective of this study was to determine whether a history of diabetes during pregnancy, as a marker of perinatal glucose intolerance, increases the odds of a diagnosis of low milk supply at a Breastfeeding Medicine Clinic (BMC). MATERIALS AND METHODS: A case-control analysis was conducted of electronic medical records for BMC visits <90 days postpartum. Diabetes was defined as documentation of gestational, type 1, or type 2 diabetes. Cases were defined as those with a low milk supply diagnosis but without latch or nipple problems, and controls as those with latch or nipple problems but without low milk supply. A sensitivity analysis was then conducted by expanding cases to include all low milk supply diagnoses, and controls to include any diagnoses except low milk supply. Odds ratios (OR) and 95% confidence intervals (CI) for diabetes were calculated in cases versus controls, including adjustment for cesarean delivery, preterm birth, polycystic ovary syndrome, hypothyroidism, and infertility. RESULTS: In the primary analysis, 14.9% of 175 cases versus 6.2% of 226 controls had a history of diabetes during pregnancy (OR 2.6 [95% CI 1.3-5.2]; adjusted OR 2.4 [95% CI 1.2-4.9]). In the sensitivity analysis, 14.9% of 249 cases versus 6.1% of 312 controls had diabetes in pregnancy (adjusted OR 2.4 [95% CI 1.4-4.3]). CONCLUSIONS: Women diagnosed with low milk supply were significantly more likely to have had diabetes in pregnancy compared with women with latch or nipple problems and, more generally, compared with women with any other lactation difficulty. Further research is needed to elucidate how maternal glucose intolerance may impede lactation. PMID- 26859785 TI - Human VE-Cadherin Fusion Protein as an Artificial Extracellular Matrix Enhancing the Proliferation and Differentiation Functions of Endothelial Cell. AB - In an attempt to enhance endothelial cell capture and promote the vascularization of engineered tissue, we biosynthesized and characterized the recombinant fusion protein consisting of human vascular endothelial-cadherin extracellular domain and immunoglobulin IgG Fc region (hVE-cad-Fc) to serve as a bioartificial extracellular matrix. The hVE-cad-Fc protein naturally formed homodimers and was used to construct hVE-cad-Fc matrix by stably adsorbing on polystyrene plates. Atomic force microscop assay showed uniform hVE-cad-Fc distribution with nanorod topography. The hVE-cad-Fc matrix markedly promoted human umbilical vein endothelial cells (HUVECs) adhesion and proliferation with fibroblastoid morphology. Additionally, the hVE-cad-Fc matrix improved HUVECs migration, vWF expression, and NO release, which are closely related to vascularization. Furthermore, the hVE-cad-Fc matrix activated endogenous VE-cadherin/beta-catenin proteins and effectively triggered the intracellular signals such as F-actin stress fiber, p-FAK, AKT, and Bcl-2. Taken together, hVE-cad-Fc could be a promising bioartificial matrix to promote vascularization in tissue engineering. PMID- 26859788 TI - Direct Catalytic Chemoselective alpha-Amination of Acylpyrazoles: A Concise Route to Unnatural alpha-Amino Acid Derivatives. AB - A direct copper-catalyzed highly chemoselective alpha-amination is described. Acylpyrazole proved to be a highly efficient enolate precursor of a carboxylic acid oxidation state substrate, while preactivation by a stoichiometric amount of strong base has been used in catalytic alpha-aminations. The simultaneous activation of both coupling partners, enolization and metal nitrenoid formation, was crucial for obtaining the product, and wide functional group compatibility highlighted the mildness of the present catalysis. The bidentate coordination mode was amenable to highly chemoselective activation over ketone and much more acidic nitroalkyl functionality. Deuterium exchange experiments clearly demonstrated that exclusive enolization of acylpyrazole was achieved without the formation of a nitronate. The present catalysis was applied to late-stage alpha amination, allowing for concise access to highly versatile alpha-amino acid derivatives. The product could be transformed into variety of useful building blocks. PMID- 26859787 TI - Giant magnetoresistive sensor array for sensitive and specific multiplexed food allergen detection. AB - Current common allergen detection methods, including enzyme-linked immunosorbent assays (ELISAs) and dip-stick methods, do not provide adequate levels of sensitivity and specificity for at-risk allergic patients. A method for performing highly sensitive and specific detection of multiple food allergens is thus imperative as food allergies are becoming increasingly recognized as a major healthcare concern, affecting an estimated 4% of the total population. We demonstrate first instance of sensitive and specific multiplexed detection of major peanut allergens Ara h 1 and Ara h 2, and wheat allergen Gliadin using giant magnetoresistive (GMR) sensor arrays. Commercialized ELISA kits for Ara h 1 and Ara h 2 report limits of detection (LODs) at 31.5 ng/mL and 0.2 ng/mL, respectively. In addition, the 96-well-based ELISA developed in-house for Gliadin was found to have a LOD of 40 ng/mL. Our multiplexed GMR-based assay demonstrates the ability to perform all three assays on the same chip specifically and with sensitivities at LODs about an order of magnitude lower than those of 96-well based ELISAs. LODs of GMR-based assays developed for Ara h 1, Ara h 2, and Gliadin were 7.0 ng/mL, 0.2 ng/mL, and 1.5 ng/mL, respectively, with little to no cross-reactivity. These LODs are clinically important as some patients could react strongly against such low allergen levels. Given the limitations of current industrial detection technology, multiplexed GMR-based assays provide a method for highly sensitive and specific simultaneous detection of any combination of food-product allergens, thus protecting allergic patients from life-threatening events, including anaphylaxis, by unintentional consumption. PMID- 26859786 TI - Mapping and Congenic Dissection of Genetic Loci Contributing to Hyperglycemia and Dyslipidemia in Mice. AB - BACKGROUND: Patients with dyslipidemia have an increased risk of developing type 2 diabetes, and diabetic patients often have dyslipidemia. Potential genetic connections of fasting plasma glucose with plasma lipid profile were evaluated using hyperlipidemic mice. METHODS: 225 male F2 mice were generated from BALB/cJ (BALB) and SM/J(SM) Apoe-deficient (Apoe-/-) mice and fed a Western diet for 5 weeks. Fasting plasma glucose and lipid levels of F2 mice were measured before and after 5 weeks of Western diet and quantitative trait locus (QTL) analysis was performed using data collected from these two time points. 144 SNP(single nucleotide polymorphism) markers across the entire genome were typed. RESULTS: One major QTL (logarithm of odds ratio (LOD): 6.46) peaked at 12.7 cM on chromosome 9,Bglu16, and 3 suggestive QTLs on chromosomes 15, 18 and X were identified for fasting glucose, and over 10 loci identified for lipid traits. Bglu16 was adjacent to a major QTL, Hdlq17, for high-density lipoprotein (HDL) cholesterol (LOD: 6.31, peak: 19.1 cM). A congenic strain with a donor chromosomal region harboring Bglu16 and Hdlq17 on the Apoe-/- background showed elevations in plasma glucose and HDL levels. Fasting glucose levels were significantly correlated with non-HDL cholesterol and triglyceride levels, especially on the Western diet, but only marginally correlated with HDL levels in F2 mice. CONCLUSIONS: We have demonstrated a correlative relationship between fasting glucose and plasma lipids in a segregating F2 population under hyperlipidemic conditions, and this correlation is partially due to genetic linkage between the two disorders. PMID- 26859790 TI - Direct Analysis of Gold Nanoparticles from Dried Droplets Using Substrate Assisted Laser Desorption Single Particle-ICPMS. AB - Single particle inductively coupled plasma mass spectrometry (SP-ICPMS) has been generally accepted as a powerful tool in the field of nanoanalysis. The method has usually been restricted to direct nanoparticle (NP) introduction using nebulization or microdroplet generation systems. In this work, AuNPs are introduced into ICPMS by substrate-assisted laser desorption (SALD) directly from a suitable absorbing plastic surface using a commercial ablation cell for the first time. In SALD, desorption of individual NPs is mediated using a frequency quintupled Nd:YAG laser (213 nm) operated at a rather low laser fluence. Conditions including laser fluence, laser beam scan rate, and carrier gas flow rate were optimized in order to gain the highest AuNP transport efficiency and avoid AuNP disintegration within the laser irradiation. The method was demonstrated on a well-characterized reference material, 56 nm AuNPs with a transport efficiency of 61% and commercially available 86 nm AuNPs. Feasibility of our technique for NP detection and characterization is discussed here, and the results are compared with an established technique, nebulizer SP-ICPMS. PMID- 26859789 TI - Polyradical Character of Triangular Non-Kekule Structures, Zethrenes, p Quinodimethane-Linked Bisphenalenyl, and the Clar Goblet in Comparison: An Extended Multireference Study. AB - In this work, two different classes of polyaromatic hydrocarbon (PAH) systems have been investigated in order to characterize the amount of polyradical character and to localize the specific regions of chemical reactivity: (a) the non-Kekule triangular structures phenalenyl, triangulene and a pi-extended triangulene system with high-spin ground state and (b) PAHs based on zethrenes, p quinodimethane-linked bisphenalenyl, and the Clar goblet containing varying polyradical character in their singlet ground state. The first class of structures already have open-shell character because of their high-spin ground state, which follows from the bonding pattern, whereas for the second class the open-shell character is generated either because of the competition between the closed-shell quinoid Kekule and the open-shell singlet biradical resonance structures or the topology of the pi-electron arrangement of the non-Kekule form. High-level ab initio calculations based on multireference theory have been carried out to compute singlet-triplet splitting for the above-listed compounds and to provide insight into their chemical reactivity based on the polyradical character by means of unpaired densities. Unrestricted density functional theory and Hartree-Fock calculations have been performed for comparison also in order to obtain better insight into their applicability to these types of complicated radical systems. PMID- 26859791 TI - Metal-Free Direct alpha-Selective Arylation of Boron Dipyrromethenes via Base Mediated C-H Functionalization. AB - A metal-free direct alpha-selective arylation of BODIPYs has been developed based on base-mediated C-H functionalization with easily accessible diaryliodonium salts, which provides a straightforward facile access to a variety of alpha arylBODIPY dyes. The alpha-regioselectivity was confirmed by X-ray analysis, and was studied by DFT calculation. The resultant dyes show strong absorption and emission over a broad range of spectra tunable via the simple variation of the diaryliodonium salts. PMID- 26859792 TI - Ototoxicity and cancer therapy. AB - Ototoxicity is a well-established toxicity associated with a subgroup of antineoplastic therapies that includes platinum chemotherapy, radiation or surgery involving the ear and auditory nerve, and supportive care agents such as aminoglycoside antibiotics and loop diuretics. The reported prevalence of ototoxicity in patients who have received potentially ototoxic therapy ranges from 4% to 90% depending on factors such as age of the patient population, agent(s) used, cumulative dose, and administration techniques. The impact of ototoxicity on subsequent health-related and psychosocial outcomes in these patients can be substantial, and the burden of morbidity related to ototoxic agents is particularly high in very young children. Considerable interindividual variability in the prevalence and severity of ototoxicity has been observed among patients receiving similar treatment, suggesting genetic susceptibility as a risk factor. The development and testing of otoprotective agents is ongoing; however, to the author's knowledge, no US Food and Drug Administration-approved otoprotectants are currently available. Prospective monitoring for ototoxicity allows for comparison of auditory outcomes across clinical trials, as well as for early detection, potential alterations in therapy, and auditory intervention and rehabilitation to ameliorate the adverse consequences of hearing loss. Cancer 2016;122:1647-58. (c) 2016 American Cancer Society. PMID- 26859794 TI - Laparoscopy-Guided Transthoracic Transdiaphragmatic Radiofrequency Ablation for Hepatic Tumors Located Beneath the Diaphragm. AB - BACKGROUND: It is often difficult to perform percutaneous radiofrequency ablation (RFA) for hepatic tumors beneath the diaphragm. Diaphragmatic thermal damage is one of the fatal late complications of percutaneous transdiaphragmatic RFA. Our experience with laparoscopic transthoracic transdiaphragmatic intraoperative RFA (LTTI-RFA) for hepatic tumors beneath the diaphragm is reported. METHODS: Ten patients who underwent LTTI-RFA from 2009 to 2012 were evaluated. Two cases had concomitant partial hepatectomy, and one underwent RFA for two tumors at the same time. The diagnosis was hepatocellular carcinoma in eight cases and metastatic hepatic tumors in two cases. Nine of eleven tumors were located at segments 7 and 8. Nine tumors were less than 20 mm in diameter. The patients were placed in the half left lateral decubitus position with single-lumen tube intubation. After placement of four abdominal ports, a 12-mm port was inserted in the fourth or fifth intercostal space into the diaphragm. The tumor was ablated by an RFA needle through the port. The routine follow-up consisted of laboratory tests and abdominal imaging every 3-6 months. RESULTS: The median operation time for only one tumor was 137 minutes (range, 105-187 minutes). The median number of times for ablation was three. Severe postoperative complications (>Clavien-Dindo IIIa) were observed in one case (right upper limb paralysis). The median follow-up period was 35 months (range, 11-43 months). There was no local tumor progression. Recurrent hepatic tumor appearance occurred in other parts of the liver in 6 of the 11 patients. CONCLUSIONS: Laparoscopic transthoracic transdiaphragmatic RFA is an acceptable procedure with a low rate of local recurrence. PMID- 26859796 TI - Attitudes, Beliefs, and Trends Regarding Adolescent Oncofertility Discussions: A Systematic Literature Review. AB - PURPOSE: Due to improved survival rates of adolescent cancers, increasing attention is paid to addressing patients' future quality of life after treatment. A salient quality of life issue for adolescent survivors is reproductive capacity. Discussing oncofertility, that is, cancer treatment's possible effects on fertility and fertility preservation (FP) options, is a means to address this concern by informing patients and parents regarding options available to them to prevent future struggles with infertility. This systematic literature review aggregates and summarizes the attitudes, beliefs, and patterns of behavior of all stakeholders (i.e., patients, parents, and healthcare providers) in oncofertility discussions when the patient is an adolescent (12-17 years old). METHODS: English, French, and German literature was systematically identified according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, via four databases, using several combinations of search terms. Book chapters, dissertations, and peer-reviewed qualitative and quantitative studies are included in this review. RESULTS: Adolescents and parents have similar informational and counseling needs. Both seek to be fully informed about cancer treatment's effects on fertility and FP options. Adolescents have varying experiences of oncofertility discussions and decision making due to sex and/or age differences. Parents and healthcare professionals alike sometimes underestimate the importance of fertility for adolescent cancer patients. Healthcare professionals hold various beliefs and practices with respect to adolescent oncofertility discussions. Many are cognizant of the various barriers that impede successful discussion and strive to overcome them. CONCLUSION: In order to overcome discussion barriers and meet adolescent patients and their parents' informational needs, it is essential to create and implement practice guidelines, as well as properly educate and train healthcare professionals about oncofertility issues. PMID- 26859797 TI - A qualitative investigation of factors influencing participation in bowel screening in New South Wales. AB - Issue addressed Bowel cancer is Australia's second biggest cancer killer. Yet, despite the existence of a free national bowel-screening program, participation in this program remains low. The aim of the present study was to understand the current factors contributing to this trend to help inform future strategies to increase participation. Methods Eight focus groups (n=61 in total) were conducted with participants aged 45 years and over from metropolitan and regional New South Wales (NSW). Discussions canvassed awareness, knowledge, attitudes and beliefs regarding bowel cancer and screening, and explored how these factors influenced decisions to screen. Results The low public profile of bowel cancer compared with other cancers, together with poor knowledge of its prevalence and treatability, has contributed to a low perception of risk in the community. Minimal understanding of the often-asymptomatic presentation of bowel cancer and the role of screening in prevention has appeared to compromise the perceived value of screening. In addition, confusion regarding when, and how often, individuals should screen was apparent. Knowledge of bowel cancer and screening, and its role in motivating intention to screen, emerged as a dominant theme in the data. Conclusions The present study highlights specific knowledge gaps and confusion with regard to bowel cancer and screening. Addressing these gaps through the provision of clear, coordinated information may shift attitudes to screening and increase participation. So what? Given the Australian Government's recent commitment to expand the National Bowel Cancer Screening Program, insight into what is driving current perceptions, attitudes and subsequent participation in bowel cancer screening is crucial to the development and targeting of new approaches and initiatives. PMID- 26859799 TI - Two New Genera of Fish Blood Flukes (Digenea: Aporocotylidae) from Catfishes in the Peruvian Amazon. AB - Cladocaecum tomasscholzi n. gen., n. sp. infects the heart (lumen of ventricle) of driftwood catfish, Ageneiosus inermis Linnaeus, 1766 (Siluriformes: Auchenipteridae) from the Nanay River (Amazon River Basin, near Iquitos, Peru). It differs from all other aporocotylid genera by having a highly branched intestine comprising a central cecum that terminates immediately anterior to the ovary and that has numerous laterally directed diverticula. Kritsky platyrhynchi ( Guidelli, Isaac, and Pavanelli, 2002 ) n. gen., n. comb. (= Plehniella p.) is redescribed based on paratypes plus new specimens collected from the body cavity of the type host (porthole shovelnose catfish, Hemisorubim platyrhynchos Valenciennes, 1840) (Pimelodidae) from the nearby Itaya River. Kritsky differs from Sanguinicola Plehn, 1905 , Plehniella Szidat, 1951 , Nomasanguinicola Truong and Bullard, 2013 , and Cladocaecum by the combination of having a spinous anterior sucker, an intestine comprising 6 asymmetrical ceca, a lanceolate body, a straight vas deferens, an ovary with finger-like lateral projections, a small and spheroid ootype, numerous, minute, spheroid uterine eggs, and separate genital pores. An updated list of hosts, tissues infected, and geographic localities for the catfish blood flukes (9 spp.; 5 genera) is provided. This is the first report of a fish blood fluke infecting a member of Auchenipteridae and first proposal of a new genus of blood fluke (Schistosomatoidea) from South America in 64 yr. It brings the total number of Amazonian fish blood flukes to a mere 4 species. PMID- 26859798 TI - Measuring Physical Activity and Sedentary Behavior in Youth with Type 2 Diabetes. AB - BACKGROUND: Lifestyle interventions that encourage increasing physical activity (PA) and losing weight are critical for overweight and obese youth with comorbid conditions. Assessing PA within such lifestyle intervention efforts requires measurement tool(s) that are both accurate and appropriate for these youth. This research compares PA levels and sedentary behavior in an ethnically diverse cohort of overweight/obese youth with type 2 diabetes using both accelerometry and a questionnaire previously validated in the general youth population. METHODS: Spearman's correlations were used to compare time spent sedentary and in different PA intensities between a questionnaire, the three-day PA recall (3DPAR), and an objective PA measure, the ActiGraph accelerometer, in 236 overweight/obese youth with diabetes. RESULTS: Spearman correlations between 3DPAR and accelerometer results for total PA were small and not significant (rho = 0.11, p > 0.05 for males and females). Correlations for specific PA intensities (moderate/vigorous and light) were also small and not significant. Sedentary time between instruments was significant, but weakly correlated in females (rho = 0.19, p < 0.05), but not in males (rho = 0.07, p = 0.48). CONCLUSIONS: Subjective PA measures validated in the general youth population may not be the best method for differentiating levels of movement in overweight/obese youth with type 2 diabetes, who spend most of their time in light-intensity activity and sedentary pursuits with little or no time spent in moderate/vigorous-intensity activities. Objective measures such as accelerometers that can capture the lower end of the movement scale are likely the more appropriate measures under these conditions. PMID- 26859800 TI - A Comparison of Two Mathematical Modeling Frameworks for Evaluating Sexually Transmitted Infection Epidemiology. AB - BACKGROUND: Different models of sexually transmitted infections (STIs) can yield substantially different conclusions about STI epidemiology, and it is important to understand how and why models differ. Frequency-dependent models make the simplifying assumption that STI incidence is proportional to STI prevalence in the population, whereas network models calculate STI incidence more realistically by classifying individuals according to their partners' STI status. METHODS: We assessed a deterministic frequency-dependent model approximation to a microsimulation network model of STIs in South Africa. Sexual behavior and demographic parameters were identical in the 2 models. Six STIs were simulated using each model: HIV, herpes, syphilis, gonorrhea, chlamydia, and trichomoniasis. RESULTS: For all 6 STIs, the frequency-dependent model estimated a higher STI prevalence than the network model, with the difference between the 2 models being relatively large for the curable STIs. When the 2 models were fitted to the same STI prevalence data, the best-fitting parameters differed substantially between models, with the frequency-dependent model suggesting more immunity and lower transmission probabilities. The fitted frequency-dependent model estimated that the effects of a hypothetical elimination of concurrent partnerships and a reduction in commercial sex were both smaller than estimated by the fitted network model, whereas the latter model estimated a smaller impact of a reduction in unprotected sex in spousal relationships. CONCLUSIONS: The frequency-dependent assumption is problematic when modeling short-term STIs. Frequency-dependent models tend to underestimate the importance of high-risk groups in sustaining STI epidemics, while overestimating the importance of long term partnerships and low-risk groups. PMID- 26859801 TI - Racial Differences in Receipt of Chlamydia Testing Among Medicaid-Insured Women in 2013. AB - OBJECTIVE: To estimate the percentage of young, sexually active Medicaid-insured women who were tested for chlamydia by age, race/ethnicity, and history of sexually transmitted disease (STD) diagnosis. METHODS: We used the medical diagnostic and procedural codes from Truven Health MarketScan Medicaid claims data from 10 states in 2012 and 2013 to estimate the rates of chlamydia testing in 2013 and previous STD diagnosis (diagnosed in 2012) among Medicaid-insured women aged 15-25 years who were sexually active in 2013. We also used a logit model to assess the association between chlamydia testing and women's age, race/ethnicity, and previous STD diagnosis. RESULTS: Overall, among approximately 261,000 Medicaid-insured women aged 15-25 years in 2013 who were classified as sexually active, 50.2% were tested for chlamydia in 2013. The chlamydia testing rate was 45.6% for white women and 57.5% for black women. The chlamydia testing rate was 63.5% for women diagnosed as having an STD in 2012 and 46.8% for women not diagnosed as having an STD in 2012. The chlamydia testing rate was significantly (P < 0.05) associated with previous STD diagnosis, age, and race/ethnicity in our logit model. CONCLUSIONS: Higher chlamydia testing rates among black women can be explained in part by higher rates of previous STD diagnoses. Our finding that black women have the highest chlamydia testing rates is encouraging, as improved access to STD prevention services among racial/ethnic minorities can help to reduce racial/ethnic disparities in STDs. However, chlamydia screening remains an underused preventive health service for young women of all racial and ethnic groups. PMID- 26859802 TI - Measuring Health and Quality of Life for Women Undergoing Testing and Screening for Chlamydia: A Systematic Review. AB - BACKGROUND: Most economic evaluations of interventions to prevent or control curable sexually transmitted infections (STIs), such as chlamydia, have focused on the longer-term health impacts avoided. However, there is a range of qualitative evidence suggesting that those who think that they might have an STI and/or undergo testing can experience impacts on their quality of life (QoL) at the testing and diagnosis stage. A systematic review was undertaken to identify and evaluate studies that have measured QoL and sexual health for women undergoing testing and screening for chlamydia. METHODS: A systematic review was conducted, with searches of 5 electronic databases up to the end of August 2013. Data on study characteristics, methods, and results were extracted using a standard template, and a narrative synthesis was undertaken. RESULTS: Eight studies measuring QoL and sexual health were included. The included studies measured a variety of aspects of QoL and sexual health, with a focus on psychosocial well-being. A range of validated tools were used to measure health and QoL, and "bespoke" questions were also developed. Few significant differences were found with comparator groups using generic instruments, but some impacts were found using bespoke questions. CONCLUSIONS: Although researchers have begun to examine the relationships between QoL and sexual health, there are limitations associated with the evidence available. There is, thus, a need for further research exploring sexual health and QoL for patients undergoing testing and screening for curable STIs, with a focus on analyzing the most appropriate methodological approaches in this context. PMID- 26859803 TI - Characteristics Associated With Urethral and Rectal Gonorrhea and Chlamydia Diagnoses in a US National Sample of Gay and Bisexual Men: Results From the One Thousand Strong Panel. AB - BACKGROUND: Gay and bisexual men are at elevated risk for Neisseria gonorrhoeae and Chlamydia trachomatis (GC/CT). Rectal GC/CT symptoms may be less obvious than urethral, increasing opportunities for undiagnosed rectal GC/CT. METHODS: A US national sample of 1071 gay and bisexual men completed urethral and rectal GC/CT testing and an online survey. RESULTS: In total, 6.2% were GC/CT positive (5.3% rectal, 1.7% urethral). We calculated adjusted (for education, race, age, relationship status, having health insurance, and income) odds ratios for factors associated with rectal and urethral GC/CT diagnoses. Age was inversely associated with urethral and rectal GC/CT. Compared with white men, Latinos had significantly greater odds of rectal GC/CT. Among men who reported anal sex, those reporting only insertive sex had lower odds of rectal GC/CT than did men who reported both insertive and receptive. There was a positive association between rectal GC/CT and number of male partners (<12 months), the number of anal receptive acts, receptive condomless anal sex (CAS) acts, and insertive CAS acts. Compared with those who had engaged in both insertive and receptive anal sex, those who engaged in only receptive anal sex had lower odds of urethral GC/CT. The number of male partners (<12 months) was associated with increased odds of urethral GC/CT. CONCLUSIONS: Rectal GC/CT was more common than urethral and associated with some demographic and behavioral characteristics. Our finding that insertive CAS acts was associated with rectal GC/CT highlights that providers should screen patients for GC/CT via a full range of transmission routes, lest GC/CT go undiagnosed. PMID- 26859804 TI - Recent Biomarker-Confirmed Unprotected Vaginal Sex, But Not Self-reported Unprotected Sex, Is Associated With Recurrent Bacterial Vaginosis. AB - BACKGROUND: Self-reported unprotected vaginal sex seems to increase risk of bacterial vaginosis (BV). However, the validity of self-reports is questionable, given their inconsistency with more objective measures of recent semen exposure such as detection of prostate-specific antigen (PSA). We examined whether recent unprotected sex, as measured both by PSA detection on vaginal swabs and by self report, was associated with increased BV recurrence. METHODS: We analyzed randomized trial data from nonpregnant, BV-positive adult women recruited from a sexually transmitted disease clinic. Participants received BV therapy at enrollment and were scheduled to return after 4, 12, and 24 weeks. Bacterial vaginosis (by Nugent score) and PSA were measured at each visit. We used Cox proportional hazards models to examine the association between PSA positivity and recurrent BV. We also evaluated associations between self-reported unprotected sex (ever/never since the last visit and in the last 48 hours, analyzed separately) and recurrent BV. RESULTS: Prostate-specific antigen and BV results were available for 96 women who contributed 226 follow-up visits. Prostate specific antigen positivity was associated with increased BV recurrence (adjusted hazard ratio [aHR], 2.32; 95% confidence interval [CI], 1.28-4.21). In contrast, we observed no significant increase in BV recurrence among women self-reporting unprotected sex since the last visit (aHR, 1.63; 95% CI, 0.77-3.43) or in the last 48 hours (aHR, 1.28; 95% CI, 0.70-2.36). CONCLUSIONS: Estimates from earlier studies linking self-reported unprotected sex and BV may be biased by misclassification. Biomarkers can improve measurement of unprotected sex, a critical exposure variable in sexual health research. PMID- 26859805 TI - Prevalence and Correlates of a Diagnosis of Sexually Transmitted Infection Among Young Aboriginal and Torres Strait Islander People: A National Survey. AB - BACKGROUND: Young Aboriginal and Torres Strait Islander (Aboriginal) people are recognized as a priority population for the control of sexually transmissible infections (STIs) in Australia. This article reports the prevalence of self reported STI diagnoses and their correlates among Aboriginal people aged 16 to 29 years. METHODS: Results were analyzed from a survey conducted between 2011 and 2013 at regular community events. Univariate and multivariate logistic regression models were used to identify the correlates of a history of STI diagnosis among participants who reported being sexually active and ever having been tested for STIs. All analyses were stratified by sex. RESULTS: Of the 2877 participants in this study, 2320, comprising 60% females, self-reported ever having had vaginal or anal sex, and a further subset of 1589 (68%) reported ever being tested for any of the following STIs: chlamydia, gonorrhea, syphilis, or trichomonas. Within this latter group, the proportion who reported that they had had a positive STI diagnosis was 25%. In multivariate analysis, women who reported sexual debut before the age of 16 years (prevalence ratio [PR], 1.53; 95% confidence interval, 1.16-2.81; P < 0.05), ever having had oral sex (PR, 2.66; 1.47-4.82; P < 0.001), inconsistent condom use in the past 12 months (PR, 1.71; 1.13-2.58; P < 0.012), having had sex with someone they had just met (adjusted odds ratio, 1.74; 1.21 2.50; P < 0.003), and using ecstasy (PR, 1.81; 1.16-2.81; P < 0.009) were significantly associated with a self-reported history of an STI diagnosis. For men, being older (25-29 years; PR, 2.10; 1.10-3.96; P < 0.023), being gay or bisexual (PR, 2.22; 1.16-4.27; P < 0.016), not using a condom during last sex, (PR, 1.74; 1.10-2.76; P < 0.019), past ecstasy use (PR, 1.88; 1.11-3.20; P < 0.019), and injecting drug use (PR, 2.81; 1.35-5.88); P < 0.006) were independent predictors of ever reporting being diagnosed as having an STI. DISCUSSION: In the first community-based survey of this population, a self-reported history of ever being diagnosed as having prevalent STIs was common in sexually active young Aboriginal people who reported STI testing in the past. This population requires targeted education and health service interventions to address the high burden of STIs. PMID- 26859806 TI - Predictors of Human Papillomavirus Vaccination Among Young Men Who Have Sex With Men. AB - BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection that causes anal, penile, and oropharyngeal cancers in men. Men who have sex with men (MSM) are at particularly high risk for HPV infection and HPV-related disease. Human papillomavirus vaccination is currently recommended for all MSM in the United States through age 26 years, yet little is known about HPV vaccine uptake in this population. The purpose of this study was to identify predictors of HPV vaccine uptake and barriers and facilitators to HPV vaccination that may be unique to young MSM. METHODS: Men aged 18 to 26 years (n = 336) were recruited via advertisements placed on a geospatial smartphone dating application designed for MSM. Participants completed an online survey. Correlates of vaccine uptake and provider recommendation for HPV vaccine were identified using logistic regression. RESULTS: In total, 21% of participants had received at least 1 dose of HPV vaccine. Provider recommendation was the strongest predictor of uptake such that MSM with a recommendation were more than 40 times more likely to have been vaccinated. Additional predictors of uptake included age and HPV vaccine attitudes. Predictors of provider recommendation included sexual identity, race/ethnicity, condomless anal sex, and HIV status. Psychosocial correlates and barriers and facilitators to HPV vaccination among unvaccinated men were also identified. CONCLUSIONS: Findings highlight potential disparities in HPV vaccine uptake, as well as disparities in provider recommendation practices for HPV vaccination. Future interventions should aim to clarify misconceptions, modify psychosocial beliefs, and address barriers and facilitators to HPV vaccine uptake specific to young MSM. PMID- 26859808 TI - Probable Syphilitic Aortitis Documented by Positron Emission Tomography. AB - Positron emission tomography (PET) has been used to aid in diagnosis of inflammatory and infectious disease. We describe the case of a patient with early latent syphilis with increased metabolic activity along the aorta detected via PET, suggesting probable aortitis. Three months after treatment, the PET showed apparent resolution of the aortitis. PMID- 26859807 TI - Determinants of High-Risk Human Papillomavirus Seroprevalence and DNA Prevalence in Mid-Adult Women. AB - BACKGROUND: The epidemiology of high-risk human papillomavirus (hrHPV) infections in mid-adult women is not well understood. METHODS: We conducted a cross sectional analysis of 379 women 30 to 50 years of age. Vaginal samples were tested for type-specific HPV DNA by polymerase chain reaction. Sera were tested for type-specific HPV antibodies by Luminex-based assay. Assays included 13 hrHPV types (16/18/31/33/35/39/45/51/52/56/58/59/68). Self-reported health and sexual history were ascertained. Risk factors for seropositivity and DNA positivity to hrHPV were assessed in separate Poisson regression models. RESULTS: The mean (SD) age of participants was 38.7 (6.1) years, and the median lifetime number of male sex partners was 7. Approximately two-thirds (68.1%) were seropositive for any hrHPV, 15.0% were DNA positive, and 70.7% were seropositive or DNA positive. In multivariate analyses, women who were married/living with a partner were less likely to be seropositive than single/separated women (adjusted prevalence ratio [aPR], 0.86; 95% confidence interval [CI], 0.75-0.98). Compared with never hormonal contraceptive users, current (aPR, 1.53; 95% CI, 1.01-2.29) or former (aPR, 1.64; 95% CI, 1.10-2.45) users were more likely to be seropositive. Women with a lifetime number of sex partners of 12 or more were more likely to be seropositive compared with those with 0 to 4 partners (aPR, 1.29; 95% CI, 1.06 1.56). Similar associations were seen with DNA positivity. In addition, there was a positive association between current smoking and hrHPV DNA (aPR vs. never smokers, 2.51; 95% CI, 1.40-4.49). CONCLUSIONS: Seventy-one percent of mid-adult women had evidence of current or prior hrHPV infection. Measures of probable increased exposure to HPV infection were associated with both seropositivity and DNA positivity to hrHPV, whereas current smoking was positively associated with hrHPV DNA only. PMID- 26859809 TI - What Is the Use of Rapid Syphilis Tests in the United States? PMID- 26859810 TI - Willingness to Disclose Sexually Transmitted Infection Status to Sex Partners Among College-Aged Men in the United States. AB - Disclosure of sexually transmitted infections (STIs) to sexual partners is critical to the prevention, treatment, and control of STIs. We examine personal intra and interpersonal influences on willingness to disclose STI status among college-aged men. Participants (n = 1064) were aged 17 to 24 years and recruited from a variety of university and community venues. Using independent-samples t test, Pearson chi test, and binary logistic regression, we examined the relationship between willingness to disclose an STI and intrapersonal and interpersonal factors, including age, masculinity values, interpersonal violence, partner cell phone monitoring, alcohol and/or drug use, condom use, number and characteristics of sex partners, and previous STI. Results reveal that among college-aged men, type of sex partner and masculinity values are significant variables in predicting whether or not an individual is willing to disclose. These data can inform STI control programs to more effectively address the complex issues associated with STI disclosure to sex partners. PMID- 26859811 TI - The Magnum Phenomenon and Its Challenges for HIV/Sexually Transmitted Disease Prevention. PMID- 26859812 TI - Using human genetics to predict the effects and side-effects of drugs. AB - PURPOSE OF REVIEW: 'Genetic proxies' are increasingly being used to predict the effects of drugs. We present an up-to-date overview of the use of human genetics to predict effects and adverse effects of lipid-targeting drugs. RECENT FINDINGS: LDL cholesterol lowering variants in HMG-Coenzyme A reductase and Niemann-Pick C1 like protein 1, the targets for statins and ezetimibe, protect against ischemic heart disease (IHD). However, HMG-Coenzyme A reductase and Niemann-Pick C1-Like Protein 1-variants also increase the risk of type 2 diabetes and gallstone disease, respectively. Mutations in proprotein convertase subtilisin kexin 9 (PCSK9), apolipoprotein B, and microsomal triglyceride transfer protein cause low LDL cholesterol and protect against IHD. In addition, mutations in apolipoprotein B and microsomal triglyceride transfer protein cause hepatic steatosis, in concordance with drugs that inhibit these targets. Both mutations in PCSK9 and PCSK9-inhibition seem without adverse effects. Mutations in APOC3 cause low triglycerides and protect against IHD, and recent pharmacological APOC3 inhibition reported major reductions in plasma triglycerides. Human genetics support that low lipoprotein(a) protects against IHD, without adverse effects, and the first trial of lipoprotein(a) inhibition reduced lipoprotein(a) up to 78%. SUMMARY: Recent genetic studies have confirmed the efficacy of statins and ezetimibe in protecting against IHD. Results from human genetics support that several lipid-lowering drugs currently under development are likely to prove efficacious in protecting against IHD, without major adverse effects. PMID- 26859813 TI - Genome-wide association analysis identifies genetic variations in subjects with myalgic encephalomyelitis/chronic fatigue syndrome. AB - Myalgic encephalomyelitis, also known as chronic fatigue syndrome or ME/CFS, is a multifactorial and debilitating disease that has an impact on over 4 million people in the United States alone. The pathogenesis of ME/CFS remains largely unknown; however, a genetic predisposition has been suggested. In the present study, we used a DNA single-nucleotide polymorphism (SNP) chip representing over 906,600 known SNPs to analyze DNA from ME/CFS subjects and healthy controls. To the best of our knowledge, this study represents the most comprehensive genome wide association study (GWAS) of an ME/CFS cohort conducted to date. Here 442 SNPs were identified as candidates for association with ME/CFS (adjusted P value<0.05). Whereas the majority of these SNPs are represented in non-coding regions of the genome, 12 SNPs were identified in the coding region of their respective gene. Among these, two candidate SNPs resulted in missense substitutions, one in a pattern recognition receptor and the other in an uncharacterized coiled-coil domain-containing protein. We also identified five SNPs that cluster in the non-coding regions of T-cell receptor loci. Further examination of these polymorphisms may help identify contributing factors to the pathophysiology of ME/CFS, as well as categorize potential targets for medical intervention strategies. PMID- 26859814 TI - Obsessive-compulsive symptoms in a large population-based twin-family sample are predicted by clinically based polygenic scores and by genome-wide SNPs. AB - Variation in obsessive-compulsive symptoms (OCS) has a heritable basis, with genetic association studies starting to yield the first suggestive findings. We contribute to insights into the genetic basis of OCS by performing an extensive series of genetic analyses in a homogeneous, population-based sample from the Netherlands. First, phenotypic and genetic longitudinal correlations over a 6 year period were estimated by modeling OCS data from twins and siblings. Second, polygenic risk scores (PRS) for 6931 subjects with genotype and OCS data were calculated based on meta-analysis results from IOCDF-GC, to investigate their predictive value. Third, the contribution of measured single nucleotide polymorphisms (SNPs) to the heritability was estimated using random-effects modeling. Last, we performed an exploratory genome-wide association study (GWAS) of OCS, testing for SNP- and for gene-based associations. Stability in OCS (test retest correlation 0.63) was mainly explained by genetic stability. The PRS based on clinical samples predicted OCS in our population-based twin-family sample. SNP based heritability was estimated at 14%. GWAS revealed one SNP (rs8100480), located within the MEF2BNB gene, associated with OCS (P=2.56 * 10(-8)). Additional gene-based testing resulted in four significantly associated genes, which are located in the same chromosomal region on chromosome 19p13.11: MEF2BNB, RFXANK, MEF2BNB-MEF2B and MEF2B. Thus, common genetic variants explained a significant proportion of OCS trait variation. Genes significantly associated with OCS are expressed in the brain and involved in development and control of immune system functions (RFXANK) and regulation of gene expression of muscle specific genes (MEF2BNB). MEF2BNB also showed a suggestive association with OCD in an independent case-control study, suggesting a role for this gene in the development of OCS. PMID- 26859815 TI - Use of machine learning for behavioral distinction of autism and ADHD. AB - Although autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) continue to rise in prevalence, together affecting >10% of today's pediatric population, the methods of diagnosis remain subjective, cumbersome and time intensive. With gaps upward of a year between initial suspicion and diagnosis, valuable time where treatments and behavioral interventions could be applied is lost as these disorders remain undetected. Methods to quickly and accurately assess risk for these, and other, developmental disorders are necessary to streamline the process of diagnosis and provide families access to much-needed therapies sooner. Using forward feature selection, as well as undersampling and 10-fold cross-validation, we trained and tested six machine learning models on complete 65-item Social Responsiveness Scale score sheets from 2925 individuals with either ASD (n=2775) or ADHD (n=150). We found that five of the 65 behaviors measured by this screening tool were sufficient to distinguish ASD from ADHD with high accuracy (area under the curve=0.965). These results support the hypotheses that (1) machine learning can be used to discern between autism and ADHD with high accuracy and (2) this distinction can be made using a small number of commonly measured behaviors. Our findings show promise for use as an electronically administered, caregiver-directed resource for preliminary risk evaluation and/or pre-clinical screening and triage that could help to speed the diagnosis of these disorders. PMID- 26859817 TI - DUF1220 copy number is associated with schizophrenia risk and severity: implications for understanding autism and schizophrenia as related diseases. PMID- 26859816 TI - Chronic behavioral stress exaggerates motor deficit and neuroinflammation in the MPTP mouse model of Parkinson's disease. AB - Environmental stressor exposure is associated with a variety of age-related diseases including neurodegeneration. Although the initial events of sporadic Parkinson's disease (PD) are not known, consistent evidence supports the hypothesis that the disease results from the combined effect of genetic and environmental risk factors. Among them, behavioral stress has been shown to cause damage and neuronal loss in different areas of the brain, however, its effect on the dopaminergic system and PD pathogenesis remains to be characterized. The C57BL/6 mice underwent chronic restraint/isolation (RI) stress and were then treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), whereas the control mice were treated only with MPTP and the effect on the PD-like phenotype was evaluated. The mice that underwent RI before the administration of MPTP manifested an exaggerated motor deficit and impairment in the acquisition of motor skills, which were associated with a greater loss of neuronal tyrosine hydroxylase and astrocytes activation. By showing that RI influences the onset and progression of the PD-like phenotype, our study underlines the novel pathogenetic role that chronic behavioral stressor has in the disease process by triggering neuroinflammation and degeneration of the nigral dopaminergic system. PMID- 26859818 TI - Beta Propellar Protein-Associated Neurodegeneration: A Rare Cause of Infantile Autistic Regression and Intracranial Calcification. AB - Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of single gene disorders with distinguished clinical phenotypes and definitive imaging findings. Beta propeller protein-associated neurodegeneration (BPAN) is a subentity of NBIA with X linked dominant inheritance. In this report, we describe a girl with autistic regression, seizures, intracranial calcification, iron accumulation in substantia nigra, and globi pallidi, and diagnosis of BPAN was established based on the identification of previously described disease causing variant in WD repeat domain 45 (WDR45) gene encoding for beta propeller protein. This is the first genetically proven case from India. BPAN is an underrecognized disorder and must be considered as a differential diagnosis in children with atypical Rett features and should be enlisted among the causes for autistic regression and intracranial calcification. Pediatricians must be aware of this rare entity for establishing early diagnosis, prognostication, and genetic counseling. Treatment is usually supportive. More research is needed to explore drugs in the management of BPAN that can facilitate the autophagy and promotes cytoprotection. PMID- 26859819 TI - A comparative behavioural study of mechanical hypersensitivity in 2 pain models in rats and humans. AB - The assessment of pain sensitivity in humans has been standardized using quantitative sensory testing, whereas in animals mostly paw withdrawal thresholds to diverse stimuli are measured. This study directly compares tests used in quantitative sensory testing (pinpricks, pressure algometer) with tests used in animal studies (electronic von Frey test: evF), which we applied to the dorsal hind limbs of humans after high frequency stimulation and rats after tibial nerve transection. Both experimental models induce profound mechanical hypersensitivity. At baseline, humans and rats showed a similar sensitivity to evF with 0.2 mm diameter tips, but significant differences for other test stimuli (all P < 0.001). When expressed as force divided by circumference, baseline thresholds for 0.8 mm probes were higher than for 0.2 mm in both species (both P < 0.001) suggesting spatial summation. At similar probe diameters, ramped stimuli showed higher baseline thresholds than stepped stimuli (P < 0.01) but similar sensitivity to change. For ramped stimuli sensitivity to change was higher with small probe tips than large blunt tips in both pain models (P < 0.01 in rat, P < 0.05 in humans). These data show that rat paw withdrawal threshold to punctate stimuli (0.2 mm diameter) can be used as surrogate parameters for human mechanical pain sensitivity, but probe size and shape should be standardized. Hypersensitivity to blunt pressure-the leading positive sensory sign after peripheral nerve injury in humans-is a novel finding in the tibial nerve transection model. By testing outside the primary zone of nerve damage (rat) or activation (humans), our methods likely involve effects of central sensitization in both species. PMID- 26859821 TI - Understanding stigma and chronic pain: a-state-of-the-art review. PMID- 26859820 TI - Neuroligin 2 regulates spinal GABAergic plasticity in hyperalgesic priming, a model of the transition from acute to chronic pain. AB - Plasticity in inhibitory receptors, neurotransmission, and networks is an important mechanism for nociceptive signal amplification in the spinal dorsal horn. We studied potential changes in GABAergic pharmacology and its underlying mechanisms in hyperalgesic priming, a model of the transition from acute to chronic pain. We find that while GABAA agonists and positive allosteric modulators reduce mechanical hypersensitivity to an acute insult, they fail to do so during the maintenance phase of hyperalgesic priming. In contrast, GABAA antagonism promotes antinociception and a reduction in facial grimacing after the transition to a chronic pain state. During the maintenance phase of hyperalgesic priming, we observed increased neuroligin (nlgn) 2 expression in the spinal dorsal horn. This protein increase was associated with an increase in nlgn2A splice variant mRNA, which promotes inhibitory synaptogenesis. Disruption of nlgn2 function with the peptide inhibitor, neurolide 2, produced mechanical hypersensitivity in naive mice but reversed hyperalgesic priming in mice previously exposed to brain-derived neurotrophic factor. Neurolide 2 treatment also reverses the change in polarity in GABAergic pharmacology observed in the maintenance of hyperalgesic priming. We propose that increased nlgn2 expression is associated with hyperalgesic priming where it promotes dysregulation of inhibitory networks. Our observations reveal new mechanisms involved in the spinal maintenance of a pain plasticity and further suggest that disinhibitory mechanisms are central features of neuroplasticity in the spinal dorsal horn. PMID- 26859822 TI - The First Immediate Face Transplant in the World. PMID- 26859823 TI - Comment on "Trainee Participation Is Associated With Adverse Outcomes in Emergency General Surgery: An Analysis of the National Surgical Quality Improvement Program Database". PMID- 26859824 TI - The Genetic Basis for Variation in Sensitivity to Lead Toxicity in Drosophila melanogaster. AB - BACKGROUND: Lead toxicity presents a worldwide health problem, especially due to its adverse effects on cognitive development in children. However, identifying genes that give rise to individual variation in susceptibility to lead toxicity is challenging in human populations. OBJECTIVES: Our goal was to use Drosophila melanogaster to identify evolutionarily conserved candidate genes associated with individual variation in susceptibility to lead exposure. METHODS: To identify candidate genes associated with variation in susceptibility to lead toxicity, we measured effects of lead exposure on development time, viability and adult activity in the Drosophila melanogaster Genetic Reference Panel (DGRP) and performed genome-wide association analyses to identify candidate genes. We used mutants to assess functional causality of candidate genes and constructed a genetic network associated with variation in sensitivity to lead exposure, on which we could superimpose human orthologs. RESULTS: We found substantial heritabilities for all three traits and identified candidate genes associated with variation in susceptibility to lead exposure for each phenotype. The genetic architectures that determine variation in sensitivity to lead exposure are highly polygenic. Gene ontology and network analyses showed enrichment of genes associated with early development and function of the nervous system. CONCLUSIONS: Drosophila melanogaster presents an advantageous model to study the genetic underpinnings of variation in susceptibility to lead toxicity. Evolutionary conservation of cellular pathways that respond to toxic exposure allows predictions regarding orthologous genes and pathways across phyla. Thus, studies in the D. melanogaster model system can identify candidate susceptibility genes to guide subsequent studies in human populations. CITATION: Zhou S, Morozova TV, Hussain YN, Luoma SE, McCoy L, Yamamoto A, Mackay TF, Anholt RR. 2016. The genetic basis for variation in sensitivity to lead toxicity in Drosophila melanogaster. Environ Health Perspect 124:1062-1070; http://dx.doi.org/10.1289/ehp.1510513. PMID- 26859825 TI - Decrease of Store-Operated Ca2+ Entry and Increase of Na+/Ca2+ Exchange by Pharmacological JAK2 Inhibition. AB - BACKGROUND/AIMS: Cell proliferation and migration are regulated by cytosolic Ca2+ activity ([Ca2+]i). Mechanisms modifying [Ca2+]i include store-operated Ca(2+) entry (SOCE) accomplished by the pore-forming ion channel unit Orai1 and its regulator STIM1, as well as Ca2+ extrusion by Na+/Ca2+ exchanger NCX1. Kinases participating in the orchestration of cell proliferation include the Janus activated kinase JAK2. The present study explored the impact of pharmacological JAK2 inhibition on SOCE and Na+/Ca2+ exchange. METHODS: MCF-7 breast carcinoma cells were studied in the absence and presence of the JAK2 inhibitors TG101348 (250 nM - 1 uM) or of AG490 (20 - 40 uM). Transcript levels were quantified with RT-PCR, protein abundance with immunoblotting, [Ca2+]i with Fura-2-fluorescence, SOCE from increase of [Ca2+]i following Ca2+ re-addition after Ca(2+)-store depletion with sarcoendoplasmatic Ca(2+)-ATPase (SERCA) inhibitor thapsigargin (1 uM), and Na+/Ca2+ exchanger activity from increase of [Ca2+]i as well as Ca2+ current in whole cell patch clamp following extracellular Na+ removal. Migratory activity was determined by a wound healing assay. RESULTS: JAK2 inhibitor TG101348 (1 uM) decreased Orai1 and STIM1 protein abundance, increased NCX1 transcript levels, decreased Ca2+ release from intracellular stores, decreased SOCE, increased Ca2+ entry as well as Ca(2+)-current following extracellular Na(+)-removal, and decreased migration. Similar effects on Ca2+ release, SOCE, and Ca(2+)-entry following extracellular Na(+)-removal were observed following treatment with AG490. CONCLUSION: The present observations disclose a novel powerful mechanism regulating intracellular Ca2+ release, cellular Ca2+ entry, cellular Ca2+ extrusion and cell migration. PMID- 26859827 TI - Evolution of HIV-Associated Lymphoma Over 3 Decades. AB - INTRODUCTION: The emergence of combined antiretroviral therapy (cART) and improvements in the management of opportunistic infections have altered the HIV epidemic over the last 30 years. We aimed to assess changes to the biology and outcomes of HIV-associated lymphomas over this period at the national center for HIV oncology in the United Kingdom. METHODS: Clinical characteristics at lymphoma diagnosis have been prospectively collected since 1986, along with details of lymphoma treatment and outcomes. The clinical features and outcomes were compared between 3 decades: pre-cART decade (1986-1995), early-cART decade (1996-2005), and late-cART decade (2006-2015). RESULTS: A total of 615 patients with HIV associated lymphoma were included in the study: 158 patients in the pre-cART era, 200 patients in the early-cART era, and 257 patients in the late-cART era. In more recent decades, patients were older (P < 0.0001) and had higher CD4 cell counts (P < 0.0001) at lymphoma diagnosis. Over time, there has also been a shift in lymphoma histological subtypes, with an increase in lymphoma subtypes associated with moderate immunosuppression. The overall survival for patients with HIV-associated lymphoma has dramatically improved over the 3 decades (P < 0.0001). CONCLUSION: Over the last 30 years, the clinical demographic of HIV associated lymphomas has evolved, and the outcomes have improved. PMID- 26859826 TI - High Plasma Concentrations of Zidovudine (AZT) Do Not Parallel Intracellular Concentrations of AZT-Triphosphates in Infants During Prevention of Mother-to Child HIV-1 Transmission. AB - OBJECTIVES: Zidovudine (AZT) is mainly used to prevent mother-to-child HIV-1 transmission (PMTCT). Despite serious concerns on AZT-associated toxicity, there is little information on pharmacokinetics of intracellular AZT metabolites in infants. METHODS: We conducted a prospective study in 31 HIV-uninfected infants who received AZT for PMTCT. Blood samples were obtained from 14 infants on postdelivery days (PDD) 1, 7, 14, and 28 and from 17 infants at 0 and 4 hours after dosing on PDD-1. Plasma AZT concentrations (pAZT) and intracellular concentrations of AZT-monophosphate (icAZT-MP), diphosphate (icAZT-DP), and triphosphate (icAZT-TP) were determined. RESULTS: Plasma AZT and icAZT-MP concentrations were 2713 nmol/L and 79 fmol/10 cells in PDD-1, but decreased to 1437 nmol/L and 31 fmol/10 cells by PDD-28 (P = 0.02 and P = 0.07 for all PDDs, respectively), whereas those of icAZT-DP and icAZT-TP remained low throughout the sampling period (P = 0.29 and P = 0.61 for all PDDs, respectively) There were no differences in icAZT-TP between infants of the 2 mg/kg 4 times a day dose and 4 mg/kg twice daily dose (P = 0.25), whereas pAZT and icAZT-MP levels were higher in the latter (P < 0.01 and <0.01, respectively). The pAZT and icAZT-MP significantly increased from 0 to 4 hours after dosing (P < 0.001 and <0.001, respectively), whereas icAZT-DP, icAZT-TP levels were not changed (P = 0.41 and 0.33, respectively). CONCLUSIONS: The level of icAZT-TP did not change with age, time, or a single dose despite the wide range of pAZT concentration. A safer dosage needs to be determined because high pAZT levels do not parallel those of icAZT-TP. PMID- 26859830 TI - Gender Difference in the Epidemiological Association between Metabolic Syndrome and Olfactory Dysfunction: The Korea National Health and Nutrition Examination Survey. AB - Metabolic syndrome (MetS) is associated with a higher risk of morbidity and/or mortality for various chronic diseases. The aim of this study was to investigate the relationships of MetS and its components with olfactory dysfunction in a representative Korean population. We analyzed the data from the Korean National Health and Nutrition Examination Survey (2008-2010). A total of 11,609 adults who underwent otolaryngological examination were evaluated. The olfactory function was classified as normosmia or hyposmia by a self-report questionnaire according to the sense problems of smell during the past 3 months. MetS was diagnosed if a participant had at least three of the following: (1) WC >=90 cm in men and >=80 cm in women; (2) fasting blood sugar >= 100 mg/dL or medication use for elevated glucose; (3) fasting triglyceride >= 150 mg/dL or cholesterol-lowering medication use; (4) HDL-cholesterol <40 mg/dL in men and <50 mg/dL in women or cholesterol lowering medication use; and (5) SBP >= 130 mmHg and/or DBP >= 85 mmHg or antihypertensive drug use for patients with a history of hypertension. The prevalence of olfactory dysfunction in the study population was 6.3%. The prevalence of olfactory dysfunction was significantly higher in older people with MetS than in those without MetS in both sexes (male, 42.0 +/- 3.4% vs. 34.7 +/- 0.9%, p = 0.0354; female, 46.2 +/- 2.8% vs. 37.8 +/- 0.8%, p = 0.0026). However, elevated waist circumference, elevated fasting glucose, elevated triglycerides, reduced HDL cholesterol, elevated blood pressure, severe stress, depressed mood, and suicidal ideation were significantly associated with olfactory dysfunction only in women. After controlling for confounders, olfactory dysfunction was significantly associated with MetS (odds ratio, 1.352; 95% confidence interval, 1.005-1.820) only in women. MetS are associated with olfactory dysfunction only in Korean women. PMID- 26859828 TI - Brief Report: HIV Drug Resistance in Adults Failing Early Antiretroviral Treatment: Results From the HIV Prevention Trials Network 052 Trial. AB - Early initiation of antiretroviral treatment (ART) reduces HIV transmission and has health benefits. HIV drug resistance can limit treatment options and compromise use of ART for HIV prevention. We evaluated drug resistance in 85 participants in the HIV Prevention Trials Network 052 trial who started ART at CD4 counts of 350-550 cells per cubic millimeter and failed ART by May 2011; 8.2% had baseline resistance and 35.3% had resistance at ART failure. High baseline viral load and less education were associated with emergence of resistance at ART failure. Resistance at ART failure was observed in 7 of 8 (87.5%) participants who started ART at lower CD4 cell counts. PMID- 26859831 TI - Extracting duration information in a picture category decoding task using hidden Markov Models. AB - OBJECTIVE: Adapting classifiers for the purpose of brain signal decoding is a major challenge in brain-computer-interface (BCI) research. In a previous study we showed in principle that hidden Markov models (HMM) are a suitable alternative to the well-studied static classifiers. However, since we investigated a rather straightforward task, advantages from modeling of the signal could not be assessed. APPROACH: Here, we investigate a more complex data set in order to find out to what extent HMMs, as a dynamic classifier, can provide useful additional information. We show for a visual decoding problem that besides category information, HMMs can simultaneously decode picture duration without an additional training required. This decoding is based on a strong correlation that we found between picture duration and the behavior of the Viterbi paths. MAIN RESULTS: Decoding accuracies of up to 80% could be obtained for category and duration decoding with a single classifier trained on category information only. SIGNIFICANCE: The extraction of multiple types of information using a single classifier enables the processing of more complex problems, while preserving good training results even on small databases. Therefore, it provides a convenient framework for online real-life BCI utilizations. PMID- 26859829 TI - Surveillance of Canine Rabies in the Central African Republic: Impact on Human Health and Molecular Epidemiology. AB - BACKGROUND: Although rabies represents an important public health threat, it is still a neglected disease in Asia and Africa where it causes tens of thousands of deaths annually despite available human and animal vaccines. In the Central African Republic (CAR), an endemic country for rabies, this disease remains poorly investigated. METHODS: To evaluate the extent of the threat that rabies poses in the CAR, we analyzed data for 2012 from the National Reference Laboratory for Rabies, where laboratory confirmation was performed by immunofluorescence and PCR for both animal and human suspected cases, and data from the only anti-rabies dispensary of the country and only place where post exposure prophylaxis (PEP) is available. Both are located in Bangui, the capital of the CAR. For positive samples, a portion of the N gene was amplified and sequenced to determine the molecular epidemiology of circulating strains. RESULTS: In 2012, 966 exposed persons visited the anti-rabies dispensary and 632 received a post-exposure rabies vaccination. More than 90% of the exposed persons were from Bangui and its suburbs and almost 60% of them were under 15-years of age. No rabies-related human death was confirmed. Of the 82 samples from suspected rabid dogs tested, 69 were confirmed positive. Most of the rabid dogs were owned although unvaccinated. There was a strong spatiotemporal correlation within Bangui and within the country between reported human exposures and detection of rabid dogs (P<0.001). Phylogenetic analysis indicated that three variants belonging to Africa I and II lineages actively circulated in 2012. CONCLUSIONS: These data indicate that canine rabies was endemic in the CAR in 2012 and had a detrimental impact on human health as shown by the hundreds of exposed persons who received PEP. Implementation of effective public health interventions including mass dog vaccination and improvement of the surveillance and the access to PEP are urgently needed in this country. PMID- 26859832 TI - Improving Education in Medical Statistics: Implementing a Blended Learning Model in the Existing Curriculum. AB - BACKGROUND: Although recent studies report on the benefits of blended learning in improving medical student education, there is still no empirical evidence on the relative effectiveness of blended over traditional learning approaches in medical statistics. We implemented blended along with on-site (i.e. face-to-face) learning to further assess the potential value of web-based learning in medical statistics. METHODS: This was a prospective study conducted with third year medical undergraduate students attending the Faculty of Medicine, University of Belgrade, who passed (440 of 545) the final exam of the obligatory introductory statistics course during 2013-14. Student statistics achievements were stratified based on the two methods of education delivery: blended learning and on-site learning. Blended learning included a combination of face-to-face and distance learning methodologies integrated into a single course. RESULTS: Mean exam scores for the blended learning student group were higher than for the on-site student group for both final statistics score (89.36+/-6.60 vs. 86.06+/-8.48; p = 0.001) and knowledge test score (7.88+/-1.30 vs. 7.51+/-1.36; p = 0.023) with a medium effect size. There were no differences in sex or study duration between the groups. Current grade point average (GPA) was higher in the blended group. In a multivariable regression model, current GPA and knowledge test scores were associated with the final statistics score after adjusting for study duration and learning modality (p<0.001). CONCLUSION: This study provides empirical evidence to support educator decisions to implement different learning environments for teaching medical statistics to undergraduate medical students. Blended and on site training formats led to similar knowledge acquisition; however, students with higher GPA preferred the technology assisted learning format. Implementation of blended learning approaches can be considered an attractive, cost-effective, and efficient alternative to traditional classroom training in medical statistics. PMID- 26859833 TI - Assessment of the Relation between the Expression of Oxaliplatin Transporters in Colorectal Cancer and Response to FOLFOX-4 Adjuvant Chemotherapy: A Case Control Study. AB - BACKGROUND: Adjuvant chemotherapy for colorectal cancer is mainly based on the combination of 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX-4). The pharmacological target of oxaliplatin remains intracellular and therefore dependent on its entry into cells. The intracellular distribution of oxaliplatin is mediated by organic cation transporters 1, 2 and 3 (OCT1, 2 and 3), copper transporter 1 (CTR1) and ATPase Cu2+ transporting beta polypeptide (ATP7B) and may modulate the efficacy of oxaliplatin-based chemotherapy. The aim of this study was to perform a retrospective study to assess the relation between the expression of oxaliplatin transporters in colorectal cancer before chemotherapy and the response to FOLFOX-4 adjuvant chemotherapy in responder and non-responder patients. METHODS: This retrospective study was conducted at a single center (University Hospital of Clermont-Ferrand, France). The target population was patients with resectable colorectal cancer operated between 2006 and 2013. Inclusion criteria were defined for the responder patients as no cancer recurrence 3 years after the end of chemotherapy, and for the non-responder patients as cancer recurrence within 1 year. Other inclusion criteria were stages IIb-IV cancers, first-line adjuvant FOLFOX-4 chemotherapy, and the availability of resected primary tumor samples. Exclusion criteria were preoperative chemotherapy and/or radiotherapy, a targeted therapy, other anticancer drugs, cancer recurrence between the first and the third year after the end of chemotherapy and follow-up < 3 years. Immunostaining of oxaliplatin transporters (OCT1, 2, 3, CTR1 and ATP7B) and Ki-67 was assessed in tumor samples. RESULTS: Retrospectively, 31 patients have been selected according to inclusion and exclusion criteria (15 responders and 16 non-responders). Before FOLFOX-4 regimen, OCT3 expression was significantly lower in responder patients compared to non-responders (p<0.001). According to multivariate analysis, OCT3 remains an independent criterion for adjuvant FOLFOX chemotherapy response (p = 0.039). No significant relation is reported between chemotherapy response and the expression of OCT1 (p = 0.49), OCT2 (p = 0.09), CTR1 (p = 0.45), ATP7B (p = 0.94) and Ki-67 (p = 0.34) in tumors. CONCLUSIONS: High expression of OCT3 could be an independent factor related to resistance to FOLFOX-4 chemotherapy. PMID- 26859834 TI - Aortic VCAM-1: an early marker of vascular inflammation in collagen-induced arthritis. AB - Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). There are limited experimental data on vascular involvement in arthritis models. To study the link between CVD and inflammation in RA, we developed a model of vascular dysfunction and articular inflammation by collagen-induced arthritis (CIA) in C57Bl/6 (B6) mice. We studied the expression of vascular inflammatory markers in CIA with and without concomitant hyperlipidic diet (HD). Collagen-induced arthritis was induced with intradermal injection of chicken type-II collagen followed by a boost 21 days later. Mice with and without CIA were fed a standard diet or an HD for 12 weeks starting from the day of the boost. Arthritis severity was evaluated with a validated clinical score. Aortic mRNA levels of vascular cell adhesion molecule-1 (VCAM-1), inducible nitric oxide synthase (iNOS) and interleukin-17 were analysed by quantitative RT-PCR. Vascular cell adhesion molecule-1 localization in the aortic sinus was determined by immunohistochemistry. Atherosclerotic plaque presence was assessed in aortas. Collagen-induced arthritis was associated with increased expression of VCAM-1, independent of diet. VCAM-1 overexpression was detectable as early as 4 weeks after collagen immunization and persisted after 15 weeks. The HD induced atheroma plaque formation and aortic iNOS expression regardless of CIA. Concomitant CIA and HD had no additive effect on atheroma or VCAM-1 or iNOS expression. CIA and an HD diet induced a distinct and independent expression of large-vessel inflammation markers in B6 mice. This model may be relevant for the study of CVD in RA. PMID- 26859835 TI - Heat Shock Protein 27 Plays a Pivotal Role in Myofibroblast Differentiation and in the Development of Bleomycin-Induced Pulmonary Fibrosis. AB - Heat shock protein 27 (HSP27) is a member of the small molecular weight HSP family. Upon treatment with transforming growth factor beta1 (TGF-beta1), we observed upregulation of HSP27 along with that of alpha-smooth muscle actin (alpha-SMA), a marker of myofibroblast differentiation, in cultured human and mouse lung fibroblasts. Furthermore, by using siRNA knockdown, we demonstrated that HSP27 was involved in cell survival and upregulation of fibronectin, osteopontin (OPN) and type 1 collagen, all functional markers of myofibroblast differentiation, in TGF-beta1-treated MRC-5 cells. In lung tissues of bleomycin treated mice, HSP27 was strongly upregulated and substantially co-localized with alpha-SMA, OPN and type I collagen but not with proSP-C (a marker of type II alveolar epithelial cells), E-cadherin (a marker of epithelial cells) or F4/80 (a marker of macrophages). A similar co-localization of HSP27 and alpha-SMA was observed in lung tissues of patients with idiopathic pulmonary fibrosis. Furthermore, airway delivery of HSP27 siRNA effectively suppressed bleomycin induced pulmonary fibrosis in mice. Collectively, our findings indicate that HSP27 is critically involved in myofibroblast differentiation of lung fibroblasts and may be a promising therapeutic target for lung fibrotic diseases. PMID- 26859836 TI - Biological activity of the bryostatin analog Merle 23 on mouse epidermal cells and mouse skin. AB - Bryostatin 1, a complex macrocyclic lactone, is the subject of multiple clinical trials for cancer chemotherapy. Although bryostatin 1 biochemically functions like the classic mouse skin tumor promoter phorbol 12-myristate 13-acetate (PMA) to bind to and activate protein kinase C, paradoxically, it fails to induce many of the typical phorbol ester responses, including tumor promotion. Intense synthetic efforts are currently underway to develop simplified bryostatin analogs that preserve the critical functional features of bryostatin 1, including its lack of tumor promoting activity. The degree to which bryostatin analogs maintain the unique pattern of biological behavior of bryostatin 1 depends on the specific cellular system and the specific response. Merle 23 is a significantly simplified bryostatin analog that retains bryostatin like activity only to a limited extent. Here, we show that in mouse epidermal cells the activity of Merle 23 was either similar to bryostatin 1 or intermediate between bryostatin 1 and PMA, depending on the specific parameter examined. We then examined the hyperplastic and tumor promoting activity of Merle 23 on mouse skin. Merle 23 showed substantially reduced hyperplasia and was not tumor promoting at a dose comparable to that for PMA. These results suggest that there may be substantial flexibility in the design of bryostatin analogs that retain its lack of tumor promoting activity. (c) 2016 Wiley Periodicals, Inc. PMID- 26859837 TI - Genetic and environmental factors in vascular dementia: an update of blood brain barrier dysfunction. AB - Vascular dementia (VaD) describes a combination of both cognitive and behavioural manifestations associated with variable brain lesions of vascular origin. While vascular risk factors have been implicated in VaD, the relationship is most evident when the factors are considered together and not individually. This review will examine the significance of the integrity of blood brain barrier (BBB) tight junction (TJ) proteins - occludin and claudins in the pathophysiology of VaD. Specifically, some of the genetic contributors to VaD, namely those responsible for the integrity of the BBB, will be reviewed in detail. Moreover, environmental factors will be considered in conjunction with these genes to examine how the interaction of environmental and genetic factors contributes to one's susceptibility to VaD. PMID- 26859838 TI - Seasonal Variation in Shell Calcification of Planktonic Foraminifera in the NE Atlantic Reveals Species-Specific Response to Temperature, Productivity, and Optimum Growth Conditions. AB - Using shells collected from a sediment trap series in the Madeira Basin, we investigate the effects of seasonal variation of temperature, productivity, and optimum growth conditions on calcification in three species of planktonic Foraminifera. The series covers an entire seasonal cycle and reflects conditions at the edge of the distribution of the studied species, manifesting more suitable growth conditions during different parts of the year. The seasonal variation in seawater carbonate saturation at the studied site is negligible compared to other oceanic regions, allowing us to assess the effect of parameters other than carbonate saturation. Shell calcification is quantified using weight and size of individual shells. The size-weight scaling within each species is robust against changes in environmental parameters, but differs among species. An analysis of the variation in calcification intensity (size-normalized weight) reveals species specific response patterns. In Globigerinoides ruber (white) and Globigerinoides elongatus, calcification intensity is correlated with temperature (positive) and productivity (negative), whilst in Globigerina bulloides no environmental forcing is observed. The size-weight scaling, calcification intensity, and response of calcification intensity to environmental change differed between G. ruber (white) and G. elongatus, implying that patterns extracted from pooled analyses of these species may reflect their changing proportions in the samples. Using shell flux as a measure of optimum growth conditions, we observe significant positive correlation with calcification intensity in G. elongatus, but negative correlation in G. bulloides. The lack of a consistent response of calcification intensity to optimum growth conditions is mirrored by the results of shell size analyses. We conclude that calcification intensity in planktonic Foraminifera is affected by factors other than carbonate saturation. These factors include temperature, productivity, and optimum growth conditions, but the strength and sign of the relationships differ among species, potentially complicating interpretations of calcification data from the fossil record. PMID- 26859839 TI - Correction: EpCAM-Independent Enrichment of Circulating Tumor Cells in Metastatic Breast Cancer. PMID- 26859840 TI - Cyber War Game in Temporal Networks. AB - In a cyber war game where a network is fully distributed and characterized by resource constraints and high dynamics, attackers or defenders often face a situation that may require optimal strategies to win the game with minimum effort. Given the system goal states of attackers and defenders, we study what strategies attackers or defenders can take to reach their respective system goal state (i.e., winning system state) with minimum resource consumption. However, due to the dynamics of a network caused by a node's mobility, failure or its resource depletion over time or action(s), this optimization problem becomes NP complete. We propose two heuristic strategies in a greedy manner based on a node's two characteristics: resource level and influence based on k-hop reachability. We analyze complexity and optimality of each algorithm compared to optimal solutions for a small-scale static network. Further, we conduct a comprehensive experimental study for a large-scale temporal network to investigate best strategies, given a different environmental setting of network temporality and density. We demonstrate the performance of each strategy under various scenarios of attacker/defender strategies in terms of win probability, resource consumption, and system vulnerability. PMID- 26859842 TI - Impact of Nitrification on the Formation of N-Nitrosamines and Halogenated Disinfection Byproducts within Distribution System Storage Facilities. AB - Distribution system storage facilities are a critical, yet often overlooked, component of the urban water infrastructure. This study showed elevated concentrations of N-nitrosodimethylamine (NDMA), total N-nitrosamines (TONO), regulated trihalomethanes (THMs) and haloacetic acids (HAAs), 1,1 dichloropropanone (1,1-DCP), trichloroacetaldehyde (TCAL), haloacetonitriles (HANs), and haloacetamides (HAMs) in waters with ongoing nitrification as compared to non-nitrifying waters in storage facilities within five different chloraminated drinking water distribution systems. The concentrations of NDMA, TONO, HANs, and HAMs in the nitrifying waters further increased upon application of simulated distribution system chloramination. The addition of a nitrifying biofilm sample collected from a nitrifying facility to its non-nitrifying influent water led to increases in N-nitrosamine and halogenated DBP formation, suggesting the release of precursors from nitrifying biofilms. Periodic treatment of two nitrifying facilities with breakpoint chlorination (BPC) temporarily suppressed nitrification and reduced precursor levels for N-nitrosamines, HANs, and HAMs, as reflected by lower concentrations of these DBPs measured after re establishment of a chloramine residual within the facilities than prior to the BPC treatment. However, BPC promoted the formation of halogenated DBPs while a free chlorine residual was maintained. Strategies that minimize application of free chlorine while preventing nitrification are needed to control DBP precursor release in storage facilities. PMID- 26859844 TI - Transcriptome-wide patterns of divergence during allopatric evolution. AB - Recent studies have revealed repeated patterns of genomic divergence associated with species formation. Such patterns suggest that natural selection tends to target a set of available genes, but is also indicative that closely related taxa share evolutionary constraints that limit genetic variability. Studying patterns of genomic divergence among populations within the same species may shed light on the underlying evolutionary processes. Here, we examine transcriptome-wide divergence and polymorphism in the marine copepod Tigriopus californicus, a species where allopatric evolution has led to replicate sets of populations with varying degrees of divergence and hybrid incompatibility. Our analyses suggest that relatively small effective population sizes have resulted in an exponential decline of shared polymorphisms during population divergence and also facilitated the fixation of slightly deleterious mutations within allopatric populations. Five interpopulation comparisons at three different stages of divergence show that nonsynonymous mutations tend to accumulate in a specific set of proteins. These include proteins with central roles in cellular metabolism, such as those encoded in mtDNA, but also include an additional set of proteins that repeatedly show signatures of positive selection during allopatric divergence. Although our results are consistent with a contribution of nonadaptive processes, such as genetic drift and gene expression levels, generating repeatable patterns of genomic divergence in closely related taxa, they also indicate that adaptive evolution targeting a specific set of genes contributes to this pattern. Our results yield insights into the predictability of evolution at the gene level. PMID- 26859843 TI - MicroRNAs as Biomarkers for Acute Atrial Remodeling in Marathon Runners (The miRathon Study--A Sub-Study of the Munich Marathon Study). AB - INTRODUCTION: Physical activity is beneficial for individual health, but endurance sport is associated with the development of arrhythmias like atrial fibrillation. The underlying mechanisms leading to this increased risk are still not fully understood. MicroRNAs are important mediators of proarrhythmogenic remodeling and have potential value as biomarkers in cardiovascular diseases. Therefore, the objective of our study was to determine the value of circulating microRNAs as potential biomarkers for atrial remodeling in marathon runners (miRathon study). METHODS: 30 marathon runners were recruited into our study and were divided into two age-matched groups depending on the training status: elite (ER, >=55 km/week, n = 15) and non-elite runners (NER, <=40 km/week, n = 15). All runners participated in a 10 week training program before the marathon. MiRNA plasma levels were measured at 4 time points: at baseline (V1), after a 10 week training period (V2), immediately after the marathon (V3) and 24h later (V4). Additionally, we obtained clinical data including serum chemistry and echocardiography at each time point. RESULTS: MiRNA plasma levels were similar in both groups over time with more pronounced changes in ER. After the marathon miR 30a plasma levels increased significantly in both groups. MiR-1 and miR-133a plasma levels also increased but showed significant changes in ER only. 24h after the marathon plasma levels returned to baseline. MiR-26a decreased significantly after the marathon in elite runners only and miR-29b showed a non-significant decrease over time in both groups. In ER miRNA plasma levels showed a significant correlation with LA diameter, in NER miRNA plasma levels did not correlate with echocardiographic parameters. CONCLUSION: MiRNAs were differentially expressed in the plasma of marathon runners with more pronounced changes in ER. Plasma levels in ER correlate with left atrial diameter suggesting that circulating miRNAs could potentially serve as biomarkers of atrial remodeling in athletes. PMID- 26859845 TI - Effects of Mentoring Speed Dating as an Innovative Matching Tool in Undergraduate Medical Education: A Mixed Methods Study. AB - OBJECTIVES: Choosing the right mentor is crucial for effective mentorship. Yet, many medical students have difficulties finding a suitable mentor. Thus we developed mentoring speed dating (MSD) as a promising matching tool to connect students and faculty mentors successfully. The purpose of this study was to explore mentees' and mentors' experience with MSD and investigate the impact of MSD on the perceived mentorship quality and continuance of the mentoring relationship. METHODS: The authors completed a mixed methods study at the University Medical Center Hamburg-Eppendorf, Germany, between June 2011 and March 2014. They conducted four focus groups with mentees and mentors who participated in a mentoring speed dating event and analyzed transcripts using conventional content analysis with inductive categorizing. In addition, three mentoring cohorts (two matched via MSD, one matched via conventional online profiles) were surveyed on mentorship satisfaction and the 1-year continuance of their mentorship was monitored. Fifteen mentees and fifteen mentors participated in the focus groups. The authors identified several themes such as short and long term benefits of MSD and fulfillment of expectations. Benefits included finding out about the personal connection, matching expectations, providing an efficient overview of candidates. The survey was completed by 93 students (n = 29 without MSD; n = 64 with MSD). Independent t-tests and multivariate analysis of variance were used to analyze the impact of MSD on student's mentorship satisfaction. RESULTS: There were significant differences in responses to the items "Commitment of mentor" (p = .019) and "Constructive feedback" (p = .038) among the students who attended MSD and the students without MSD. After one year far more mentoring relationships existed among those mentees who participated in MSD in comparison to the "no MSD group". CONCLUSION: MSD is a valuable matching tool with beneficial effects on the mentorship quality. It enhances essential factors in the mentoring relationship such as commitment and satisfaction. PMID- 26859846 TI - The Prevalence of Drug-Resistant Tuberculosis in Mainland China: An Updated Systematic Review and Meta-Analysis. AB - BACKGROUND: In recent years, drug resistant tuberculosis (DR-TB) particularly the emergence of multi-drug-resistant tuberculosis (MDR-TB) has become a major public health issue. The most recent study regarding the prevalence of drug-resistant tuberculosis in mainland China was a meta-analysis published in 2011, and the subjects from the included studies were mostly enrolled before 2008, thus making it now obsolete. Current data on the national prevalence of DR-TB is needed. This review aims to provide a comprehensive and up-to-date assessment of the status of DR-TB epidemic in mainland China. METHODS: A systematic review and meta-analysis of studies regarding the prevalence of drug-resistant tuberculosis in mainland China was performed. Pubmed/MEDLINE, EMBASE, the Cochrane central database, the Chinese Biomedical Literature Database and the China National Knowledge Infrastructure Database were searched for studies relevant to drug-resistant tuberculosis that were published between January 1, 2012 and May 18, 2015. Comprehensive Meta-Analysis (V2.2, Biostat) software was used to analyse the data. RESULTS: A total of fifty-nine articles, published from 2012 to 2015, were included in our review. The result of this meta-analysis demonstrated that among new cases, the rate of resistance to any drug was 20.1% (18.0%-22.3%; n/N = 7203/34314) and among retreatment cases, the rate was 49.8% (46.0%-53.6%; n/N = 4155/8291). Multi-drug resistance among new and retreatment cases was 4.8% (4.0% 5.7%; n/N = 2300/42946) and 26.3% (23.1%-29.7%; n/N = 3125/11589) respectively. The results were significantly heterogeneous (p<0.001, I2 tests). Resistance to isoniazid was the most common resistance observed, and HRSE (H: isoniazid; R: rifampicin; S: streptomycin; E: ethambutol) was the most common form for MDR among both new and retreatment cases. Different drug resistance patterns were found by subgroup analysis according to geographic areas, subject enrolment time, and methods of drug susceptibility test (DST). CONCLUSIONS: The prevalence of resistance to any drug evidently dropped for both new and retreatment cases, and multi-drug resistance declined among new cases but became more prevalent among retreatment cases compared to the data before 2008. Therefore, drug-resistant tuberculosis, particularly multi-drug-resistant tuberculosis among retreatment TB cases is a public health issue in China that requires a constant attention in order to prevent increase in MDR-TB cases. PMID- 26859848 TI - Mental Imagery, Impact, and Affect: A Mediation Model for Charitable Giving. AB - One of the puzzling phenomena in philanthropy is that people can show strong compassion for identified individual victims but remain unmoved by catastrophes that affect large numbers of victims. Two prominent findings in research on charitable giving reflect this idiosyncrasy: The (1) identified victim and (2) victim number effects. The first of these suggests that identifying victims increases donations and the second refers to the finding that people's willingness to donate often decreases as the number of victims increases. While these effects have been documented in the literature, their underlying psychological processes need further study. We propose a model in which identified victim and victim number effects operate through different cognitive and affective mechanisms. In two experiments we present empirical evidence for such a model and show that different affective motivations (donor-focused vs. victim-focused feelings) are related to the cognitive processes of impact judgments and mental imagery. Moreover, we argue that different mediation pathways exist for identifiability and victim number effects. PMID- 26859847 TI - Flavokawain C Inhibits Cell Cycle and Promotes Apoptosis, Associated with Endoplasmic Reticulum Stress and Regulation of MAPKs and Akt Signaling Pathways in HCT 116 Human Colon Carcinoma Cells. AB - Flavokawain C (FKC) is a naturally occurring chalcone which can be found in Kava (Piper methysticum Forst) root. The present study evaluated the effect of FKC on the growth of various human cancer cell lines and the underlying associated mechanisms. FKC showed higher cytotoxic activity against HCT 116 cells in a time- and dose-dependent manner in comparison to other cell lines (MCF-7, HT-29, A549 and CaSki), with minimal toxicity on normal human colon cells. The apoptosis inducing capability of FKC on HCT 116 cells was evidenced by cell shrinkage, chromatin condensation, DNA fragmentation and increased phosphatidylserine externalization. FKC was found to disrupt mitochondrial membrane potential, resulting in the release of Smac/DIABLO, AIF and cytochrome c into the cytoplasm. Our results also revealed that FKC induced intrinsic and extrinsic apoptosis via upregulation of the levels of pro-apoptotic proteins (Bak) and death receptors (DR5), while downregulation of the levels of anti-apoptotic proteins (XIAP, cIAP 1, c-FlipL, Bcl-xL and survivin), resulting in the activation of caspase-3, -8 and -9 and cleavage of poly(ADP-ribose) polymerase (PARP). FKC was also found to cause endoplasmic reticulum (ER) stress, as suggested by the elevation of GADD153 protein after FKC treatment. After the cells were exposed to FKC (60MUM) over 18hrs, there was a substantial increase in the phosphorylation of ERK 1/2. The expression of phosphorylated Akt was also reduced. FKC also caused cell cycle arrest in the S phase in HCT 116 cells in a time- and dose-dependent manner and with accumulation of cells in the sub-G1 phase. This was accompanied by the downregulation of cyclin-dependent kinases (CDK2 and CDK4), consistent with the upregulation of CDK inhibitors (p21Cip1 and p27Kip1), and hypophosphorylation of Rb. PMID- 26859849 TI - Angiotensin II and Anti Diuretic Hormone Exert Synergistic Effects on Thick Ascending Limb Transport in Spontaneously Hypertensive Rats. AB - BACKGROUND: Sodium reabsorption is increased in the thick ascending limb (TAL) of Henle in several hypertensive models. In this segment, while transport is increased by ADH via cAMP, sodium reabsorption results from Ang II-induced superoxide (O2(-)) production. Surprisingly, it is unknown whether these mechanisms overlap in hypertension. We hypothesized that Ang II and ADH have accumulative effects on TAL's transport during hypertension. METHODS: The effect of ADH/Ang II in TALs from spontaneously hypertensive rats (SHR) on oxygen consumption (QO2), cAMP and O2(-) was measured. RESULTS: Basal QO2 was 113.3 +/- 14.2 nmol O2/min/mg protein. Addition of ADH (1 nM) increased QO2 by 198%. In the presence of ADH, Ang II (1 nM) elicited a QO2 transient response and then rose to 321.5 +/- 28.3 (p = 0.003 vs. ADH). These accumulative effects could be due to nitric oxide synthase (NOS) uncoupling, lower Ang II ability to decrease cAMP or increased O2(-). We first measured QO2 using a NOS inhibitor. Pretreatment with L NAME did not block the observed interaction (p = 0.001 Ang II vs. ADH). Also, Ang II blocked the ADH-stimulated cAMP accumulation in TAL of SHRs. In the presence of ADH, Ang II increased O2(-) production in TALs from SHR by 309% (p = 0.015 vs. basal). The O2(-) scavenger tempol blocked the Ang II effects on QO2. In the presence of the NADPH oxidase inhibitor apocynin, the accumulative effects of ADH and Ang II were abolished. We conclude that (1) in SHR, Ang II has accumulative effects on ADH-stimulated transport; (2) this effect is mediated by AT1 receptors, and increased O2(-) production. PMID- 26859851 TI - Role of Serum Brain Derived Neurotrophic Factor and Central N-Acetylaspartate for Clinical Response under Antidepressive Pharmacotherapy. AB - BACKGROUND: The predictive therapeutic value of brain derived neurotrophic factor (BDNF) and its changes associated with the use of specific antidepressants are still unclear. In this study, we examined BDNF as a peripheral and NAA as a central biomarker over the time course of antidepressant treatment to specify both of their roles in the response to the medication and clinical outcome. METHODS: We examined serum BDNF (ELISA kit) in a sample of 76 (47 female and 29 male) depressed patients in a naturalistic setting. BDNF was assessed before medication and subsequently after two, four and six weeks of antidepressant treatment. Additionally, in fifteen patients, N-acetylaspartate (NAA) was measured in the anterior cingulate cortex (ACC) with magnetic resonance spectroscopy (MRS). Over a time course of six weeks BDNF and NAA were also examined in a group of 41 healthy controls. RESULTS: We found significant lower serum BDNF concentrations in depressed patients compared to the sample of healthy volunteers before and after medication. BDNF and clinical symptoms decreased significantly in the patients over the time course of antidepressant treatment. Serum BDNF levels at baseline predicted the symptom outcome after eight weeks. Specifically, responders and remitters had lower serum BDNF at baseline than the nonresponders and nonremitters. NAA was slightly decreased but not significantly lower in depressed patients when compared with healthy controls. During treatment period, NAA showed a tendency to increase. LIMITATIONS: A relative high drop-out rate and possibly, a suboptimal observation period for BDNF. CONCLUSION: Our data confirm serum BDNF as a biomarker of depression with a possible role in response prediction. However, our findings argue against serum BDNF increase being a prerequisite to depressive symptom reduction. PMID- 26859850 TI - In Vivo Evaluation of Blood Based and Reference Tissue Based PET Quantifications of [11C]DASB in the Canine Brain. AB - This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT) in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT), obtained via the one- and two- tissue compartment model (1-TC, 2-TC) and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC). For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722). Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs. PMID- 26859852 TI - Altered hemispheric lateralization of white matter pathways in developmental dyslexia: Evidence from spherical deconvolution tractography. AB - This study examines the structural integrity and the hemispheric lateralization patterns of four major association fiber pathways in a group of French dyslexic children and age-matched controls (from 9 to 14 years), using high angular diffusion imaging combined with spherical deconvolution tractography. Compared with age-matched controls, dyslexic children show increased hindrance-modulated oriented anisotropy (HMOA) in the right superior longitudinal fasciculus (SLF). They also show a reduced leftward asymmetry of the inferior fronto-occipital fasciculus (IFOF) and an increased rightward asymmetry of the second branch of the SLF (SLF II). The lateralization pattern of IFOF and SLF II also accounts for individual differences in dyslexic children's reading abilities. These data provide evidence for an abnormal lateralization of occipito-frontal and parieto frontal pathways in developmental dyslexia. PMID- 26859854 TI - [New techniques can radically change health care]. PMID- 26859853 TI - Jump-landing biomechanics following a 4-week real-time feedback intervention and retention. AB - BACKGROUND: Poor neuromuscular control can increase the risk of anterior cruciate ligament (ACL) injury. Landing with decreased knee and hip flexion may increase the risk of lower extremity injury. Feedback interventions have demonstrated changes in jump-landing biomechanics. Traditional feedback (TF), provided after task completion, includes critical factors to focus on during jump-landing. Real time feedback (RTF), provided while completing the task, may be superior for improving jump-landing biomechanics. This investigation evaluated the effect of RTF+TF compared to TF and a control group in changing lower extremity jump landing biomechanics following a 4-week feedback intervention and a 1-week no feedback retention. METHODS: Participants completed 12 feedback sessions over 4 weeks. At each session, participants performed 6 sets of 6 jumps off a 30 cm box. Participants were provided TF or RTF+TF following each set of jumps. Participants were tested at baseline, immediately following the 4-week intervention and following a 1-week retention. The control group was tested at two time points 4 weeks apart. FINDINGS: Acquisition analysis: RTF+TF and TF groups demonstrated greater change in peak hip flexion angles and peak knee flexion angles compared to the control group following the intervention. TF and RTF+TF groups demonstrated a greater decrease in peak vertical ground reaction force compared to the control group. No significant differences were observed between groups in the retention analysis. INTERPRETATION: This study provides evidence of acquisition of biomechanical changes following a 4-week feedback intervention. Future research should further investigate the retention of biomechanical changes, the optimal length of feedback interventions and transfer of learned biomechanics to similar athletic tasks. PMID- 26859855 TI - [Hypothyroidism during pregnancy risks the child's neurocognitive development. New guidelines and remaining knowledge gaps]. AB - Thyroid abnormalities are common during pregnancy and can affect pregnancy outcome. In 2012, the working group for endocrinology was assigned by SFOG to develop evidence based guidelines for their management. There is high quality evidence that untreated clinical hypothyroidism increases the risk of pregnancy and fetal complications. Subclinical hypothyroidism is associated with pregnancy complications. The presence of TPO-antibodies is linked to miscarriage and premature birth. It is uncertain whether subclinical hypothyroidism/maternal TPO antibodies adversely affect the child's neurocognitive development. Reference intervals for TSH among pregnant women in Sweden need to be established. PMID- 26859856 TI - [What leadership style is needed in health care?]. PMID- 26859857 TI - [Always take health anxiety seriously]. PMID- 26859858 TI - [Insufficient knowledge about mild TSH elevation during pregnancy. Still too early for screening within the Swedish maternity health system]. AB - Guidelines of the Swedish Society of Obstetricians and Gynecologists suggest screening for thyroid disease in early pregnancy in accordance with some international guidelines. A recommendation to treat all pregnant women with an increase of serum TSH above the trimester specific reference limit with levothyroxine is included. In a commentary on these guidelines from the authors, published in this issue of Lakartidningen, a more cautious approach to this controversial standpoint is noticed. Until further experience is gained and the scientific problem is resolved it is unjustified to implement a broad sceening procedure for thyroid disease in the Swedish maternity health system. PMID- 26859860 TI - [Not Available]. PMID- 26859859 TI - [The altruism of blood donors is abused]. PMID- 26859861 TI - [Not Available]. PMID- 26859862 TI - [Long "screen time" can lead to depression among young people]. PMID- 26859863 TI - [Not Available]. PMID- 26859864 TI - Social perception: How do 6-month-old infants look at pointing gestures? AB - The study explored 6-month-old infants' ability to follow a pointing gesture in a dynamic social context. The infants were presented with a video of a model pointing to one of two toys. The pointing gesture was performed either normally (with arm and hand pointing at the same direction), with a stick, or the model's arm and hand pointing in different directions (at different toys). The results indicate that infants at this age reliably followed pointing performed normally. PMID- 26859865 TI - Determination of long-range scalar (1)H-(1)H coupling constants responsible for polarization transfer in SABRE. AB - SABRE (Signal Amplification By Reversible Exchange) nuclear spin hyperpolarization method can provide strongly enhanced NMR signals as a result of the reversible association of small molecules with para-hydrogen (p-H2) at an iridium metal complex. The conversion of p-H2 singlet order to enhanced substrate proton magnetization within such complex is driven by the scalar coupling interactions between the p-H2 derived hydrides and substrate nuclear spins. In the present study these long-range homonuclear couplings are experimentally determined for several SABRE substrates using an NMR pulse sequence for coherent hyperpolarization transfer at high magnetic field. Pyridine and pyrazine derivatives appear to have a similar ~1.2 Hz (4)J coupling to p-H2 derived hydrides for their ortho protons, and a much lower (5)J coupling for their meta protons. Interestingly, the (4)J hydride-substrate coupling for five-membered N heterocyclic substrates is well below 1 Hz. PMID- 26859867 TI - Electrohydraulic lithotripsy as a salvage option for stone impaction during double-balloon endoscope-assisted ERCP. PMID- 26859866 TI - Outcome of EMR as an alternative to surgery in patients with complex colon polyps. AB - BACKGROUND AND AIMS: Patients with complex colon polyps were traditionally referred for surgery to avoid adverse events associated with endoscopic resection. Recent advances in endoscopic imaging as well as endoscopic hemostasis and clip closure allow for the use of EMR as an alternative to surgery for such lesions. To determine the outcome of treatment of complex colon polyps with EMR as an alternative to surgery, we conducted a retrospective observational study. METHODS: Two hundred three patients with complex colon polyps were referred to an EMR center as an alternative to surgery. Patients underwent a protocol-driven EMR. The primary endpoint was the complete resection rate. Secondary endpoints were safety, residual adenoma rate, and incidence of missed synchronous polyps. RESULTS: EMR was performed in 155 patients and was deferred in 48 patients who were referred to surgery. EMR specimens revealed benign polyps in 149 and cancer in 6 patients. EMR adverse events occurred in 7 patients, requiring hospitalization in 5 of them. None of the patients died as a result of their adverse events. Surveillance colonoscopy at 4 to 6 months after resection of a benign lesion in 137 patients revealed residual adenoma at the scar site in 6 patients and additional synchronous precancerous lesions in 117 patients that were not removed by the referring endoscopist. None underwent surgery for failure of EMR. The overall precancerous lesion burden was 2.83 per patient, the adenoma burden was 2.13 per patient, and the serrated polyp burden was .69 per patient. CONCLUSIONS: EMR can be used instead of surgery for complex colon polyps in 75% of patients with few adverse events and few residual adenomas at resection sites. In addition, careful repeat examination of the entire colon for synchronous lesions overlooked by the referring endoscopist is required for most patients. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01827241.). PMID- 26859868 TI - Translation regulation via nascent polypeptide-mediated ribosome stalling. AB - As the nascent polypeptide chain is being synthesized, it passes through a tunnel within the large ribosomal subunit. Interaction between the nascent polypeptide chain and the ribosomal tunnel can modulate the translation rate and induce translational stalling to regulate gene expression. In this article, we highlight recent structural insights into how the nascent polypeptide chain, either alone or in cooperation with co-factors, can interact with components of the ribosomal tunnel to regulate translation via inactivating the peptidyltransferase center of the ribosome and inducing ribosome stalling. PMID- 26859871 TI - An intra-cerebral abscess in a patient with Eisenmenger syndrome: An unusual case. AB - INTRODUCTION: We present an unusual case where a large intra-cerebral abscess with severe complications was treated successfully with medical management alone in a patient with Eisenmenger syndrome. PRESENTATION OF CASE: A 40 year old patient with Eisenmenger syndrome presented with a seven day history of headache, neck pain and intermittent vomiting and fever. The only neurological examination finding was blurred vision. MRI revealed a large left occipital lobe abscess, which subsequently ruptured into the lateral ventricle with associated ventriculitis and hydrocephalus. This complicated abscess was successfully treated with intravenous antibiotics alone, with complete resolution of the abscess and hydrocephalus on MRI at 13 months post-diagnosis. DISCUSSION: Patients with congenital cyanotic heart conditions, like Eisenmenger syndrome, are at increased risk of developing intra-cerebral abscesses. Effectively managing large abscesses with associated intra-ventricular rupture and hydrocephalus in these patients without any form of surgical intervention, including aspiration, is extremely rare. CONCLUSION: Patients with congenital cyanotic heart disease who develop large intra-cerebral abscesses with severe complications, which would normally warrant surgical intervention, have the potential to be successfully treated with antibiotics alone with excellent outcome. PMID- 26859870 TI - Transcriptomics Modeling of the Late-Gestation Fetal Pituitary Response to Transient Hypoxia. AB - BACKGROUND: The late-gestation fetal sheep responds to hypoxia with physiological, neuroendocrine, and cellular responses that aid in fetal survival. The response of the fetus to hypoxia represents a coordinated effort to maximize oxygen transfer from the mother and minimize wasteful oxygen consumption by the fetus. While there have been many studies aimed at investigating the coordinated physiological and endocrine responses to hypoxia, and while immunohistochemical or in situ hybridization studies have revealed pathways supporting the endocrine function of the pituitary, there is little known about the coordinated cellular response of the pituitary to the hypoxia. RESULTS: Thirty min hypoxia (from 17.0+/-1.7 to 8.0+/-0.8 mm Hg, followed by 30 min normoxia) upregulated 595 and downregulated 790 genes in fetal pituitary (123-132 days' gestation; term = 147 days). Network inference of up- and down- regulated genes revealed a high degree of functional relatedness amongst the gene sets. Gene ontology analysis revealed upregulation of cellular metabolic processes (e.g., RNA synthesis, response to estrogens) and downregulation of protein phosphorylation, protein metabolism, and mitosis. Genes found to be at the center of the network of upregulated genes included genes important for purine binding and signaling. At the center of the downregulated network were genes involved in mRNA processing, DNA repair, sumoylation, and vesicular trafficking. Transcription factor analysis revealed that both up- and down-regulated gene sets are enriched for control by several transcription factors (e.g., SP1, MAZ, LEF1, NRF1, ELK1, NFAT, E12, PAX4) but not for HIF-1, which is known to be an important controller of genomic responses to hypoxia. CONCLUSIONS: The multiple analytical approaches used in this study suggests that the acute response to 30 min of transient hypoxia in the late gestation fetus results in reduced cellular metabolism and a pattern of gene expression that is consistent with cellular oxygen and ATP starvation. In this early time point, we see a vigorous gene response. But, like the hypothalamus, the transcriptomic response is not consistent with mediation by HIF-1. If HIF-1 is a significant controller of gene expression in the fetal pituitary after hypoxia, it must be at a later time. PMID- 26859869 TI - Filament assemblies in foreign nucleic acid sensors. AB - Helical filamentous assembly is ubiquitous in biology, but was only recently realized to be broadly employed in the innate immune system of vertebrates. Accumulating evidence suggests that the filamentous assemblies and helical oligomerization play important roles in detection of foreign nucleic acids and activation of the signaling pathways to produce antiviral and inflammatory mediators. In this review, we focus on the helical assemblies observed in the signaling pathways of RIG-I-like receptors (RLRs) and AIM2-like receptors (ALRs). We describe ligand-dependent oligomerization of receptor, receptor-dependent oligomerization of signaling adaptor molecules, and their functional implications and regulations. PMID- 26859872 TI - Surgical versus conservative management of adult intussusception: Case series and review. AB - INTRODUCTION: Intussusception is the telescoping of a segment of bowel into its adjacent segment. It is a known cause of abdominal pain in the pediatric population, however, it is rare in the adult. Adults do not always present with the typical symptoms seen in young children, making the clinical diagnosis more difficult. The etiology of adult intussusception can be idiopathic, benign, or malignant. Diagnosis is most accurately made with computed tomography, which is sensitive in detecting intussusception as well as potential lead points. PRESENTATION OF CASES: This study presents four adult patients with intussusception. The first three patients are adults with idiopathic intussusception and no evidence of a lead point. The fourth case involves intussusception secondary to a jejunal carcinoid tumor which was treated surgically. Each case has unique features in terms of length and number of intussusceptions, duration of symptoms, and recurrence. DISCUSSION: Surgical treatment was once argued to be universally appropriate for adult intussusceptions; however, with increased use of advanced imaging, newer literature is demonstrating that this is not true in all cases. Idiopathic intussusception presents with nonspecific symptoms and can be managed with supportive care when the history and clinical picture indicate low probability of a neoplasm. CONCLUSION: This study aims to raise awareness to the potential diagnosis and management of intussusceptions, particularly the symptomatic idiopathic type in the young adult. PMID- 26859873 TI - A Comparison of the Effects of Burst and Tonic Spinal Cord Stimulation on Hyperalgesia and Physical Activity in an Animal Model of Neuropathic Pain. AB - BACKGROUND: Parameters of spinal cord stimulation (SCS) play a role in its effectiveness and may impact SCS mechanisms and outcomes. For example, SCS applied in a bursting pattern may result in better pain relief than that for tonic SCS for neuropathic pain. We tested the effectiveness of different SCS pulse frequencies given at 2 different burst frequencies in an animal model of neuropathic pain. METHODS: After Sprague-Dawley rats were anesthetized, neuropathic pain was induced using the spared nerve injury model, and an epidural SCS lead was implanted in the upper lumber spinal cord. One of the 8 different SCS parameters was delivered daily for 4 days at 90% motor threshold 2 weeks after nerve injury. Four burst patterns were administered at 4- or 40-Hz frequency with a train of 4 pulses at frequencies of 60, 500, and 1000 Hz. Sham and tonic patterns at 16, 60, and 160 Hz were chosen as controls. Paw withdrawal threshold was assessed before the surgery and 15 minutes before, during, and after SCS daily for 4 days. Physical activity (distance, crossing, rearing, and grooming) was assessed before surgery, before SCS on day 1, and after SCS on day 4. RESULTS: Animals showed a decrease in paw withdrawal threshold and physical activity levels 2 weeks after nerve injury. During stimulation, burst SCS with pulse frequencies of 60, 500, or 1000 Hz were more effective for improving paw withdrawal threshold than sham and tonic SCS at 16 Hz. Burst SCS with higher pulse frequencies (500 and 1000 Hz) than 60-Hz SCS and burst SCS with higher pulse frequencies (1000 Hz) than 160-Hz SCS were more effective. In addition, tonic SCS at 160 Hz and burst SCS with higher pulse frequencies (500 and 1000 Hz) significantly increased the distance traveled. Burst SCS at 4 Hz with pulse frequency of 1000 Hz also increased the number of crossings when compared with sham control and tonic SCS at 16 Hz. CONCLUSIONS: The current study shows that a variety of SCS pulse frequencies applied with a burst frequency result in greater improvement in hyperalgesia and activity levels than tonic SCS in a neuropathic pain model during stimulation. PMID- 26859874 TI - The Effects of the Toll-Like Receptor 4 Antagonist, Ibudilast, on Sevoflurane's Minimum Alveolar Concentration and the Delayed Remifentanil-Induced Increase in the Minimum Alveolar Concentration in Rats. AB - BACKGROUND: Ultralow doses of naloxone, an opioid and toll-like receptor 4 antagonist, blocked remifentanil-induced hyperalgesia and the associated increase in the minimum alveolar concentration (MAC), but not tolerance. The aim was to determine the effects of the toll-like receptor 4 antagonist, ibudilast, on the MAC in the rat and how it might prevent the effects of remifentanil. METHODS: Male Wistar rats were randomly allocated to 5 treatment groups (n = 7 per group): 10 mg/kg ibudilast intraperitoneally, 240 ug/kg/h remifentanil IV, ibudilast plus remifentanil, remifentanil plus naloxone IV, or saline. The sevoflurane MAC was determined 3 times in every rat and every day (days 0, 2, and 4): baseline (MAC A) and 2 further determinations were made after treatments, 1.5 hours apart (MAC B and MAC-C). RESULTS: A reduction in baseline MAC was produced on day 0 by ibudilast, remifentanil, remifentanil plus ibudilast, remifentanil plus naloxone (P < 0.01), but not saline. Similar effects were found on days 2 and 4. A tolerance to remifentanil was found on days 0, 2, and 4, which neither ibudilast nor naloxone prevented. The MAC increase produced by remifentanil on day 4 (P = 0.001) was prevented by either ibudilast or naloxone. CONCLUSIONS: Ibudilast, besides reducing the MAC, prevented the delayed increase in baseline MAC produced by remifentanil but not the increase in MAC caused by tolerance to remifentanil. PMID- 26859875 TI - Emulsified Isoflurane Protects Against Transient Focal Cerebral Ischemia Injury in Rats via the PI3K/Akt Signaling Pathway. AB - BACKGROUND: Phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) pathway activation may promote neuronal survival via neuroprotection during inflammation after cerebral ischemia. In this study, we investigated whether IV pretreatment with emulsified isoflurane (EI) could decrease ischemic brain injury related to the PI3K/Akt pathway. METHODS: Male Sprague-Dawley rats received different doses of IV EI (1, 2, 4, or 8 mL/kg/h) or Intralipid (8 mL/kg/h) for 30 minutes (n = 6 12 per group), followed by middle cerebral artery occlusion (MCAO) for 100 minutes to induce transient focal ischemia. The neurologic score and infarct volume were measured 48 hours after MCAO. Immunostaining, Western blot analysis, and an enzyme-linked immunosorbent assay were used to assess EI effects on the cell inflammatory response, high-mobility group box-1 release, and phosphorylated Akt (expression. LY294002, a PI3K inhibitor, was also infused into the ventricular space before EI to determine the effect of EI. RESULTS: Four milliliters per kilogram per hour of EI reduced the infarct size (21.08 +/- 11.24 vs 37.09 +/- 10.46, P = 0.006), improved neurologic scores after MCAO (1.13 +/- 0.48 vs 1.95 +/- 0.65, P = 0.015), significantly reinforced neuronal survival (982.7 +/- 364.4 vs 439.8 +/- 278.4, P = 0.036), and inhibited CD68 macrophage/macroglial infiltration in the ischemic core (188.2 +/- 49.1 vs 282 +/ 49.4, P = 0.018) compared with the vehicle group. In the EI pretreatment group, the serum high-mobility group box-1 concentration (3.62 +/- 0.72 vs 5.73 +/- 0.65, P < 0.001) was decreased, and the cerebral phosphorylated Akt level (50.33 +/- 4.73 vs 37.5 +/- 3.11, P = 0.007) was increased at 48 hours, which was inhibited by LY294002 compared with the vehicle group (5.31 +/- 0.72 vs 5.73 +/- 0.65, P = 0.216; 43.00 +/- 4.84 vs 37.5 +/- 3.11, P = 0.091). CONCLUSIONS: These findings suggest that EI pretreatment protects against ischemic brain injury via the inhibition of cerebral inflammation and is associated with the PI3K-Akt pathway in rats with MCAO. This drug may be a novel therapeutic agent for patients after stroke. PMID- 26859876 TI - The Importance of the Saphenous Nerve in Ankle Surgery. AB - BACKGROUND: Recent evidence suggests that the saphenous nerve may be involved in the innervation of deeper structures at the medial ankle. In this study, we sought to determine the consistency and variability of the saphenous nerve innervation at the distal tibia and medial ankle joint capsule. METHODS: One hundred three lower extremities from 52 embalmed cadavers were dissected to identify the deep branches of saphenous nerve along its distal course. RESULTS: In all specimens, the saphenous nerve had branches, emerging between 3.9 and 8.2 cm above the medial malleolus, to the periosteum of the distal tibia and the medial capsule of the ankle joint. CONCLUSIONS: Deep branches of the saphenous nerve innervate the periosteum of the distal tibia and talocrural capsule. PMID- 26859877 TI - Amnesia of the Operating Room in the B-Unaware and BAG-RECALL Clinical Trials. AB - BACKGROUND: Patient memories of the operating room (OR) may serve as the informational basis for assessing satisfaction with individual anesthesiologists. Furthermore, the provision of clinically important information may assume that perioperative memories are retained. Studies assessing the extent of perioperative amnesia and factors associated with perioperative amnesia are sparse. Therefore, we assessed patient amnesia of the OR and of the preoperative holding area in hospitals where midazolam is typically administered in the preoperative holding area and evaluated whether midazolam dose administered in the preoperative holding area and patient age were associated with amnesia of the OR before induction of anesthesia. METHODS: This was a retrospective study among 7750 adult patients who had general anesthesia and participated in the B-Unaware and Bispectral Index or Anesthetic Gas to Reduce Explicit Recall (BAG-RECALL) clinical trials. The last location the patient remembered before induction of anesthesia and the first location they remembered after induction of anesthesia were determined through a modified Brice questionnaire administered over the phone 30 days postoperatively. Regarding the preoperative period, patients were excluded if their last memory was unclear with respect to location before induction of anesthesia or if they were recruited at Winnipeg, where midazolam was typically first administered in the OR. Midazolam dose (mg/kg) administered in the preoperative holding area was divided into quartiles. Poisson regression models were used to calculate age- and multivariable-adjusted odds ratios (95% confidence intervals [CIs]) for the association between midazolam dose and amnesia of the OR before induction of anesthesia. RESULTS: Of the 5339 patients included, 59.5% (95% CI, 58.2-60.9) of patients had amnesia of the OR before induction of anesthesia. In addition, 44.1% (95% CI, 42.8-45.7) last remembered the preoperative holding area, and 15.4% (95% CI, 14.4-16.4) only had preoperative memories before the holding area. The percentages of patients with amnesia of the OR before induction of anesthesia differed according to age groups: 50.7% (95% CI, 47.7%-53.7%) in patients aged 18 to 47 years versus 70.0% (95% CI, 67.0%-72.9%) in patients aged 73 to 99 years. Patients in the highest midazolam quartile had an adjusted prevalence ratio of 1.31 (95% CI, 1.22-1.42) for amnesia of the OR compared with those who did not receive midazolam. CONCLUSIONS: In hospitals where patients typically receive midazolam in the preoperative holding area, the majority of patients do not remember the OR, and a clinically relevant number of patients does not remember the preoperative holding area. If additional studies produce results indicating that a substantial proportion of patients has amnesia of the anesthesiologist, these findings would argue against the validity of assessing patient satisfaction with individual anesthesiologists providing exclusively OR care in such hospitals. Furthermore, if additional studies yield findings suggesting patient amnesia of the preoperative holding area, these results would suggest reconsideration of providing clinically important information only in the preoperative holding area. Older age and midazolam-induced anterograde amnesia are probably associated with impaired perioperative memories. PMID- 26859878 TI - Ultrasound Assessment of the Prokinetic Effect of Erythromycin in Trauma Patients with a Full Stomach: A Case Series. AB - In this preliminary prospective noninterventional study, we assessed the prokinetic effect of 3 mg*kg erythromycin in nonfasted emergency trauma patients. Ultrasonographic measurements of the antral area were performed 30 minutes and immediately before the erythromycin infusion and serially at 30, 60, and 90 minutes after the start of the infusion. Gastric emptying rates before and after erythromycin infusion, and at each 30-minute period after erythromycin infusion, were then calculated. We found that gastric emptying rates were increased after erythromycin infusion although gastric content and volume remained similar. PMID- 26859879 TI - Influence of implantation on the electrochemical properties of smooth and porous TiN coatings for stimulation electrodes. AB - OBJECTIVE: To determine whether changes in electrochemical properties of porous titanium nitride (TiN) electrodes as a function of time after implantation are different from those of smooth TiN electrodes. APPROACH: Eight smooth and 8 porous TiN coated electrodes were implanted in 8 rats. Before implantation, voltage transients, cyclic voltammograms and impedance spectra were recorded in phosphate buffered saline (PBS). After implantation, these measurements were done weekly to investigate how smooth and porous electrodes were affected by implantation. MAIN RESULTS: The electrode capacitance of the porous TiN electrodes decreased more than the capacitance of the smooth electrodes due to acute implantation under fast measurement conditions (such as stimulation pulses). This indicates that protein adhesion presents a greater diffusion limitation for counter-ions for the porous than for the smooth electrodes. The changes in electrochemical properties during the implanted period were similar for smooth and porous TiN electrodes, indicating that cell adhesion poses a similar diffusion limitation for smooth and porous electrodes. SIGNIFICANCE: This knowledge can be used to optimize the porous structure of the TiN film, so that the effect of protein adhesion on the electrochemical properties is diminished. Alternatively, an additional coating could be applied on the porous TiN that would prevent or minimize protein adhesion. PMID- 26859880 TI - Hospital Admissions, Transfers and Costs of Guillain-Barre Syndrome. AB - BACKGROUND: Guillain-Barre syndrome (GBS) has a highly variable clinical course, leading to frequent transfers within and between hospitals and high associated costs. We defined the current admissions, transfers and costs in relation to disease severity of GBS. METHODS: Dutch neurologists were requested to report patients diagnosed with GBS between November 2009 and November 2010. Information regarding clinical course and transfers was obtained via neurologists and general practitioners. RESULTS: 87 GBS patients were included with maximal GBS disability score of 1 or 2 (28%), 3 or 4 (53%), 5 (18%) and 6 (1%). Four mildly affected GBS patients were not hospital admitted. Of the 83 hospitalized patients 68 (82%) were initially admitted at a neurology department, 4 (5%) at an ICU, 4 (5%) at pediatrics, 4 (5%) at pediatrics neurology and 3 (4%) at internal medicine. Median hospital stay was 17 days (IQR 11-26 days, absolute range 1-133 days). Transfers between departments or hospitals occurred in 33 (40%) patients and 25 (30%) were transferred 2 times or more. From a cost-effectiveness perspective 21 (25%) of the admissions was suboptimal. Median costs for hospital admission of GBS patients were 15,060 Euro (IQR 11,226-23,683). Maximal GBS disability score was significantly correlated with total length of stay, number of transfers, ICU admission and costs. CONCLUSIONS: Hospital admissions for GBS patients are highly heterogeneous, with frequent transfers and higher costs for those with more severe disease. Future research should aim to develop prediction models to early identify the most cost-effective allocation in individual patients. PMID- 26859881 TI - Vitamin C Intake and Pancreatic Cancer Risk: A Meta-Analysis of Published Case Control and Cohort Studies. AB - BACKGROUND: Observational studies inconsistently reported the relationship between vitamin C intake and risk of pancreatic cancer. We conducted a meta analysis of published case-control and cohort studies to quantify the association. METHODS: Potentially eligible studies were found on PubMed and EMBASE databases through May 31, 2015. A random-effects model was assigned to compute summary point estimates with corresponding 95% confidence intervals (CIs). Subgroup and meta-regression analyses were also performed to explore sources of heterogeneity. RESULTS: Our final analyses included 20 observational studies comprising nearly 5 thousand cases of pancreatic cancer. When comparing the highest with the lowest categories of vitamin C intake, the summary odds ratio/relative risk for case-control studies (14 studies), cohort studies (6 studies) and all studies combined was 0.58 (95% CI: 0.52-0.66), 0.93 (95% CI: 0.78-1.11) and 0.66 (95% CI: 0.58-0.75), respectively. The difference in the findings between case-control and cohort studies was statistically significant (P < .001). Possible publication bias was shown in the meta-analysis of case-control studies. CONCLUSION: There is insufficient evidence to conclude any relationship between vitamin C intake and risk of pancreatic cancer. The strong inverse association observed in case-control studies may be affected by biases (eg, recall and selection biases) that particularly affect case-control studies and/or potential publication bias. Future prospective studies of vitamin C intake and pancreatic cancer are needed. PMID- 26859882 TI - DNA Inversion Regulates Outer Membrane Vesicle Production in Bacteroides fragilis. AB - Phase changes in Bacteroides fragilis, a member of the human colonic microbiota, mediate variations in a vast array of cell surface molecules, such as capsular polysaccharides and outer membrane proteins through DNA inversion. The results of the present study show that outer membrane vesicle (OMV) formation in this anaerobe is also controlled by DNA inversions at two distantly localized promoters, IVp-I and IVp-II that are associated with extracellular polysaccharide biosynthesis and the expression of outer membrane proteins. These promoter inversions are mediated by a single tyrosine recombinase encoded by BF2766 (orthologous to tsr19 in strain NCTC9343) in B. fragilis YCH46, which is located near IVp-I. A series of BF2766 mutants were constructed in which the two promoters were locked in different configurations (IVp-I/IVp-II = ON/ON, OFF/OFF, ON/OFF or OFF/ON). ON/ON B. fragilis mutants exhibited hypervesiculating, whereas the other mutants formed only a trace amount of OMVs. The hypervesiculating ON/ON mutants showed higher resistance to treatment with bile, LL-37, and human beta defensin 2. Incubation of wild-type cells with 5% bile increased the population of cells with the ON/ON genotype. These results indicate that B. fragilis regulates the formation of OMVs through DNA inversions at two distantly related promoter regions in response to membrane stress, although the mechanism underlying the interplay between the two regions controlled by the invertible promoters remains unknown. PMID- 26859884 TI - Optimal Geometrical Set for Automated Marker Placement to Virtualized Real-Time Facial Emotions. AB - In recent years, real-time face recognition has been a major topic of interest in developing intelligent human-machine interaction systems. Over the past several decades, researchers have proposed different algorithms for facial expression recognition, but there has been little focus on detection in real-time scenarios. The present work proposes a new algorithmic method of automated marker placement used to classify six facial expressions: happiness, sadness, anger, fear, disgust, and surprise. Emotional facial expressions were captured using a webcam, while the proposed algorithm placed a set of eight virtual markers on each subject's face. Facial feature extraction methods, including marker distance (distance between each marker to the center of the face) and change in marker distance (change in distance between the original and new marker positions), were used to extract three statistical features (mean, variance, and root mean square) from the real-time video sequence. The initial position of each marker was subjected to the optical flow algorithm for marker tracking with each emotional facial expression. Finally, the extracted statistical features were mapped into corresponding emotional facial expressions using two simple non-linear classifiers, K-nearest neighbor and probabilistic neural network. The results indicate that the proposed automated marker placement algorithm effectively placed eight virtual markers on each subject's face and gave a maximum mean emotion classification rate of 96.94% using the probabilistic neural network. PMID- 26859883 TI - Salivary Alterations in Rats with Experimental Chronic Kidney Disease. AB - OBJECTIVE: This study aimed to analyze changes in saliva composition and salivary secretion process of rats with chronic kidney disease induced by 5/6 nephrectomy to set the foundation for salivary studies related to CKD. METHODS: CKD was induced in Wistar rats via 5/6 nephrectomy. Blood and saliva samples were collected from Control, Sham and CKD groups at 8 and 12 weeks after the surgery. Salivation was stimulated via intraperitoneal injections of pilocarpine (1.0 mg/Kg body weight) or isoproterenol (5.0 mg/Kg body weight). Saliva was collected and immediately stored at -80 degrees C until analysis. The salivary flow rate, total protein, amylase and peroxidase activities, and urea concentrations were measured. The blood urea nitrogen (BUN) and serum creatinine concentrations were also evaluated. RESULTS: Increases in BUN and serum creatinine concentrations were observed in the CKD groups. Amylase activity was significantly reduced in response to both stimuli in the CKD groups at 8 weeks and increased in the CKD groups at 12 weeks in response to isoproterenol stimulus. The peroxidase activities of the CKD groups were significantly reduced in response to isoproterenol stimulation and were increased at 12 weeks in response to pilocarpine stimulation. Salivary urea was significantly increased in the CKD groups at 8 weeks in response to the isoproterenol stimuli and at 12 weeks in response to both salivary agonists. CONCLUSIONS: The pattern of alterations observed in this experimental model is similar to those observed in patients and clearly demonstrates the viability of 5/6 nephrectomy as an experimental model in future studies to understand the alterations in salivary compositions and in salivary glands that are elicited by CKD. PMID- 26859885 TI - Expert Opinions on Improving Femicide Data Collection across Europe: A Concept Mapping Study. AB - Femicide, defined as the killings of females by males because they are females, is becoming recognized worldwide as an important ongoing manifestation of gender inequality. Despite its high prevalence or widespread prevalence, only a few countries have specific registries about this issue. This study aims to assemble expert opinion regarding the strategies which might feasibly be employed to promote, develop and implement an integrated and differentiated femicide data collection system in Europe at both the national and international levels. Concept mapping methodology was followed, involving 28 experts from 16 countries in generating strategies, sorting and rating them with respect to relevance and feasibility. The experts involved were all members of the EU-Cost-Action on femicide, which is a scientific network of experts on femicide and violence against women across Europe. As a result, a conceptual map emerged, consisting of 69 strategies organized in 10 clusters, which fit into two domains: "Political action" and "Technical steps". There was consensus among participants regarding the high relevance of strategies to institutionalize national databases and raise public awareness through different stakeholders, while strategies to promote media involvement were identified as the most feasible. Differences in perceived priorities according to the level of human development index of the experts' countries were also observed. PMID- 26859887 TI - Correction: Contact Trees: Network Visualization beyond Nodes and Edges. PMID- 26859886 TI - Global MicroRNA Expression Profiling of Mouse Livers following Ischemia Reperfusion Injury at Different Stages. AB - Hepatic ischemia-reperfusion injury is a dynamic process consisting of two stages: ischemia and reperfusion, and triggers a cascade of physiological and biochemical events. Given the important role of microRNAs in regulating gene expression, we analyzed gene expression changes in mouse livers at sham control, ischemia stage, and reperfusion stage. We generated global expression profiles of microRNA and mRNA genes in mouse livers subjected to ischemia-reperfusion injury at the three stages, respectively. Comparison analysis showed that reperfusion injury had a distinct expression profile whereas the ischemia sample and the sham control were clustered together. Consistently, there are 69 differentially expressed microRNAs between the reperfusion sample and the sham control whereas 28 differentially expressed microRNAs between the ischemia sample and the sham control. We further identified two modes of microRNA expression changes in ischemia-reperfusion injury. Functional analysis of both the differentially expressed microRNAs in the two modes and their target mRNAs revealed that ischemia injury impaired mitochondrial function, nutrient consumption, and metabolism process. In contrast, reperfusion injury led to severe tissue inflammation that is predominantly an innate-immune response in the ischemia reperfusion process. Our staged analysis of gene expression profiles provides new insights into regulatory mechanisms of microRNAs in mouse hepatic IR injury. PMID- 26859888 TI - On the Use of Bone Remodelling Models to Estimate the Density Distribution of Bones. Uniqueness of the Solution. AB - Bone remodelling models are widely used in a phenomenological manner to estimate numerically the distribution of apparent density in bones from the loads they are daily subjected to. These simulations start from an arbitrary initial distribution, usually homogeneous, and the density changes locally until a bone remodelling equilibrium is achieved. The bone response to mechanical stimulus is traditionally formulated with a mathematical relation that considers the existence of a range of stimulus, called dead or lazy zone, for which no net bone mass change occurs. Implementing a relation like that leads to different solutions depending on the starting density. The non-uniqueness of the solution has been shown in this paper using two different bone remodelling models: one isotropic and another anisotropic. It has also been shown that the problem of non uniqueness is only mitigated by removing the dead zone, but it is not completely solved unless the bone formation and bone resorption rates are limited to certain maximum values. PMID- 26859890 TI - Baseline Characteristics and Prescription Patterns of Standard Drugs in Patients with Angiographically Determined Coronary Artery Disease and Renal Failure (CAD REF Registry). AB - BACKGROUND: Chronic kidney disease (CKD) is strongly associated with coronary artery disease (CAD). We established a prospective observational nationwide multicenter registry to evaluate current treatment and outcomes in patients with both CKD and angiographically documented CAD. METHODS: In 32 cardiological centers 3,352 CAD patients with >=50% stenosis in at least one coronary artery were enrolled and classified according to their estimated glomerular filtration rate and proteinuria into one of five stages of CKD or as a control group. RESULTS: 2,723 (81.2%) consecutively enrolled patients suffered from CKD. Compared to controls, CKD patients had a higher prevalence of diabetes, hypertension, peripheral artery diseases, heart failure, and valvular heart disease (each p<0.001). Myocardial infarctions (p = 0.02), coronary bypass grafting, valve replacements and pacemaker implantations had been recorded more frequently (each p<0.001). With advanced CKD, the number of diseased coronary vessels and the proportion of patients with reduced left ventricular ejection fraction (LVEF) increased significantly (both p<0.001). Percutaneous coronary interventions were performed less frequently (p<0.001) while coronary bypass grafting was recommended more often (p = 0.04) with advanced CKD. With regard to standard drugs in CAD treatment, prescriptions were higher in our registry than in previous reports, but beta-blockers (p = 0.008), and angiotensin-converting enzyme inhibitors and/or angiotensin-receptor blockers (p<0.001) were given less often in higher CKD stages. In contrast, in the subgroup of patients with moderately to severely reduced LVEF the prescription rates did not differ between CKD stages. In-hospital mortality increased stepwise with each CKD stage (p = 0.02). CONCLUSIONS: In line with other studies comprising CKD cohorts, patients' morbidity and in-hospital mortality increased with the degree of renal impairment. Although cardiologists' drug prescription rates in CAD-REF were higher than in previous studies, they were still lower especially in advanced CKD stages compared to cohorts treated by nephrologists. PMID- 26859889 TI - G-Protein alpha-Subunit Gsalpha Is Required for Craniofacial Morphogenesis. AB - The heterotrimeric G protein subunit Gsalpha couples receptors to activate adenylyl cyclase and is required for the intracellular cAMP response and protein kinase A (PKA) activation. Gsalpha is ubiquitously expressed in many cell types; however, the role of Gsalpha in neural crest cells (NCCs) remains unclear. Here we report that NCCs-specific Gsalpha knockout mice die within hours after birth and exhibit dramatic craniofacial malformations, including hypoplastic maxilla and mandible, cleft palate and craniofacial skeleton defects. Histological and anatomical analysis reveal that the cleft palate in Gsalpha knockout mice is a secondary defect resulting from craniofacial skeleton deficiencies. In Gsalpha knockout mice, the morphologies of NCCs-derived cranial nerves are normal, but the development of dorsal root and sympathetic ganglia are impaired. Furthermore, loss of Gsalpha in NCCs does not affect cranial NCCs migration or cell proliferation, but significantly accelerate osteochondrogenic differentiation. Taken together, our study suggests that Gsalpha is required for neural crest cells-derived craniofacial development. PMID- 26859891 TI - Economic Impact of Dementia by Disease Severity: Exploring the Relationship between Stage of Dementia and Cost of Care in Taiwan. AB - OBJECTIVE: Given the shortage of cost-of-illness studies in dementia outside of the Western population, the current study estimated the annual cost of dementia in Taiwan and assessed whether different categories of care costs vary by severity using multiple disease-severity measures. METHODS: This study included 231 dementia patient-caregiver dyads in a dementia clinic at a national university hospital in southern Taiwan. Three disease measures including cognitive, functional, and behavioral disturbances were obtained from patients based on medical history. A societal perspective was used to estimate the total costs of dementia according to three cost sub-categories. The association between dementia severity and cost of care was examined through bivariate and multivariate analyses. RESULTS: Total costs of care for moderate dementia patient were 1.4 times the costs for mild dementia and doubled from mild to severe dementia among our community-dwelling dementia sample. Multivariate analysis indicated that functional declines had a greater impact on all cost outcomes as compared to behavioral disturbance, which showed no impact on any costs. Informal care costs accounted for the greatest share in total cost of care for both mild (42%) and severe (43%) dementia patients. CONCLUSIONS: Since the total costs of dementia increased with severity, providing care to delay disease progression, with a focus on maintaining patient physical function, may reduce the overall cost of dementia. The greater contribution of informal care to total costs as opposed to social care also suggests a need for more publicly-funded long-term care services to assist family caregivers of dementia patients in Taiwan. PMID- 26859892 TI - Lipoicmethylenedioxyphenol Reduces Experimental Atherosclerosis through Activation of Nrf2 Signaling. AB - OBJECTIVE: Oxidative stress is implicated in the pathogenesis of atherosclerosis, and Nrf2 is the transcriptional factor central in cellular antioxidant responses. In the present study, we investigate the effect of a dihydrolipoic acid derivative lipoicmethylenedioxyphenol (LMDP) on the progression of atherosclerosis and test whether its effect on atherosclerosis is mediated by Nrf2. METHODS AND RESULTS: Both magnetic resonance imaging (MRI) scanning and en face analysis reveal that 14 weeks of treatment with LMDP markedly reduced atherosclerotic burden in a rabbit balloon vascular injury model. Myograph analyses show decreased aortic contractile response to phenylephrine and increased aortic response to acetylcholine and insulin in LMDP-treated animals, suggesting that LMDP inhibits atherosclerosis through improving vascular function. A role of Nrf2 signaling in mediating the amelioration of vascular function by LMDP was supported by increased Nrf2 translocation into nuclear and increased expression of Nrf2 target genes. Furthermore, chemotaxis analysis with Boydem chamber shows that leukocytes isolated from LMDP-treated rabbits had reduced chemotaxis, and knock-down of Nrf2 significantly reduced the effect of LMDP on the chemotaxis of mouse macrophages. CONCLUSION: Our results support that LMDP has an anti-atherosclerotic effect likely through activation of Nrf2 signaling and subsequent inhibition of macrophage chemotaxis. PMID- 26859893 TI - Tolerability and Healthcare Utilization in Maintenance Hemodialysis Patients Undergoing Treatment for Tuberculosis-Related Conditions. AB - BACKGROUND: The incidence of tuberculosis (TB) in end-stage renal disease is significantly higher than that in the general population. Among those with kidney dysfunction, anti-TB treatment is associated with increased side effects, but the effect on healthcare utilization is unknown. Methods/Aim: To assess patient reported symptoms, adverse effects and describe changes in healthcare utilization patterns during treatment for TB, we conducted a case series (n = 12) of patients receiving maintenance hemodialysis (HD) from Mayo Clinic Dialysis Services and concurrent drug therapy for TB from January 2002 through May 2014. Healthcare utilization (hospitalizations and emergency department (ED) visits independent of hospital admission) was compared before and during treatment. RESULTS: Patients were treated for latent (n = 7) or active (n = 5) TB. The majority of patients with latent disease were treated with isoniazid (n = 5, 71%), while active disease patients received a 4-drug regimen. Adverse effects were reported in 83% of patients. Compared to measurements prior to drug initiation, serum albumin and dialysis weights were similar at 3 months. Commonly reported anti-TB drug toxicities were described. More than half (58%) of the patients were hospitalized at least once. No ED or hospital admissions occurred in the period prior to drug therapy, but healthcare utilization increased during treatment in the latent disease group (hospitalization rate per person-month: pre 0 vs. post 1). CONCLUSIONS: Among HD patients, anti-TB therapy is associated with frequently reported symptoms and increased healthcare utilization. Among this subset, patients receiving treatment for latent disease may be those with greatest increase in healthcare use. Careful monitoring and early complication detection may help optimize medication adherence and minimize hospitalizations. PMID- 26859895 TI - Raf Kinase Inhibitor Protein Expression and Prognostic Value in Soft Tissue Sarcomas. AB - OBJECTIVE: Soft tissue sarcomas (STSs) are heterogeneous tumors displaying multiple and complex molecular abnormalities with no specific pattern. Despite current therapeutic advances, the patients with STS still have a poor outcome, which makes it necessary to find out new prognostic markers. The Raf kinase inhibitory protein (RKIP) has been associated with prognosis in several human neoplasms; however, its role in STS is unknown. METHODS: In the present study RKIP expression was assessed by immunohistochemistry in a series of 87 STSs, and its expression profile was associated with the patients' pathological parameters. RESULTS: We found that RKIP is expressed in the cytoplasm of the great majority of cases, and absent in only approximately 18% of cases (16/87). Importantly, we observed that loss of RKIP expression was associated with poor outcome, constituting an independent prognostic marker. CONCLUSION: This is the first study assessing RKIP expression levels in STS. We showed that loss of RKIP expression is present in a small subset of cases; however, its absence was associated with poor survival and may be a potential marker for STS prognosis. PMID- 26859894 TI - Lower Neighborhood Socioeconomic Status Associated with Reduced Diversity of the Colonic Microbiota in Healthy Adults. AB - In the United States, there are persistent and widening socioeconomic gaps in morbidity and mortality from chronic diseases. Although most disparities research focuses on person-level socioeconomic-status, mounting evidence suggest that chronic diseases also pattern by the demographic characteristics of neighborhoods. Yet the biological mechanisms underlying these associations are poorly understood. There is increasing recognition that chronic diseases share common pathogenic features, some of which involve alterations in the composition, diversity, and functioning of the gut microbiota. This study examined whether socioeconomic-status was associated with alpha-diversity of the colonic microbiota. Forty-four healthy adults underwent un-prepped sigmoidoscopy, during which mucosal biopsies and fecal samples were collected. Subjects' zip codes were geocoded, and census data was used to form a composite indicator of neighborhood socioeconomic-status, reflecting household income, educational attainment, employment status, and home value. In unadjusted analyses, neighborhood socioeconomic-status explained 12-18 percent of the variability in alpha diversity of colonic microbiota. The direction of these associations was positive, meaning that as neighborhood socioeconomic-status increased, so did alpha-diversity of both the colonic sigmoid mucosa and fecal microbiota. The strength of these associations persisted when models were expanded to include covariates reflecting potential demographic (age, gender, race/ethnicity) and lifestyle (adiposity, alcohol use, smoking) confounds. In these models neighborhood socioeconomic-status continued to explain 11-22 percent of the variability in diversity indicators. Further analyses suggested these patterns reflected socioeconomic variations in evenness, but not richness, of microbial communities residing in the sigmoid. We also found indications that residence in neighborhoods of higher socioeconomic-status was associated with a greater abundance of Bacteroides and a lower abundance of Prevotella, suggesting that diet potentially underlies differences in microbiota composition. These findings suggest the presence of socioeconomic variations in colonic microbiota diversity. Future research should explore whether these variations contribute to disparities in chronic disease outcomes. PMID- 26859897 TI - Medicaid Program; Covered Outpatient Drugs. Final rule with comment period. AB - This final rule implements provisions of the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010 (collectively referred to as the Affordable Care Act) pertaining to Medicaid reimbursement for covered outpatient drugs (CODs). This final rule also revises other requirements related to CODs, including key aspects of their Medicaid coverage and payment and the Medicaid drug rebate program. PMID- 26859896 TI - Manual Ventilation and Sustained Lung Inflation in an Experimental Model: Influence of Equipment Type and Operator's Training. AB - AIM: To compare the influence of devices for manual ventilation and individual experience on the applied respiratory mechanics and sustained lung inflation. METHODS: A total of 114 instructors and non-instructors from the Neonatal Resuscitation Program of the Brazilian Society of Pediatrics participated in this study. Participants ventilated an intubated manikin. To evaluate respiratory mechanics and sustained lung inflation parameters, a direct comparison was made between the self-inflating bag and the T-shaped resuscitator (T-piece), followed by an analysis of the effectiveness of the equipment according to the participants' education and training. RESULTS: A difference between equipment types was observed for the tidal volume, with a median (interquartile range) of 28.5 mL (12.6) for the self-inflating bag and 20.1 mL (8.4) for the T-piece in the instructor group and 31.6 mL (14) for the self-inflating bag and 22.3 mL (8.8) for the T-piece in the non-instructor group. Higher inspiratory time values were observed with the T-piece in both groups of professionals, with no significant difference between them. The operator's ability to maintain the target pressure over the 10 seconds of sustained lung inflation was evaluated using the area under the pressure-time curve and was 1.7-fold higher with the use of the T-piece. Inspiratory pressure and mean airway pressure applied during sustained lung inflation were greater with the self-inflating bag, as evaluated between the beginning and the end of the procedure. CONCLUSION: The T-piece resulted in lower tidal volume and higher inspiratory time values, irrespective of the operator's experience, and increased the ease of performing the sustained lung inflation maneuver, as demonstrated by the maintenance of target pressure for the desired period and a higher mean airway pressure than that obtained using the self-inflating bag. PMID- 26859898 TI - Medicaid Program; Face-to-Face Requirements for Home Health Services; Policy Changes and Clarifications Related to Home Health. Final rule. AB - This final rule revises the Medicaid home health service definition consistent with section 6407 of the Patient Protection and Affordable Care Act of 2010 (the Affordable Care Act) and section 504 of the Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) to add requirements that, for home health services, physicians document, and, for certain medical equipment, physicians or certain authorized non-physician practitioners (NPP) document the occurrence of a face-to-face encounter (including through the use of telehealth) with the Medicaid eligible beneficiary within reasonable timeframes. This rule also aligns the timeframes for the face-to-face encounter with similar regulatory requirements for Medicare home health services. In addition, this rule amends the definitions of medical supplies, equipment, and appliances. We expect minimal impact with the implementation of section 6407 of the Affordable Care Act and section 504 of MACRA. We recognize that states may have budgetary implications as a result of the amended definitions of medical supplies, equipment and appliances. Specifically, this rule may expand coverage of medical supplies, equipment and appliances under the home health benefit. There will be items that had previously only been offered under certain sections of the Act that will now be covered under the home health benefit. PMID- 26859899 TI - State Health Insurance Assistance Program (SHIP). Interim final rule. AB - This rule implements a provision enacted by the Consolidated Appropriations Act of 2014 and reflects the transfer of the State Health Insurance Assistance Program (SHIP) from the Centers for Medicare & Medicaid Services (CMS), in the Department of Health and Human Services (HHS) to the Administration for Community Living (ACL) in HHS. The previous regulations were issued by CMS under the authority granted by the Omnibus Budget Reconciliation Act of 1990 (OBRA '90), Section 4360. PMID- 26859900 TI - Emotional Intelligence: one Component in the HeART of Medicine. AB - The increasing need for health care providers has contributed to a rise in the number of physician assistant (PA) programs. Unfortunately simply increasing the number of graduates to meet this increased need is not good enough. Not only must PA programs and educators make sure that graduates have the necessary medical knowledge and clinical skills but that graduates also have the ability to understand and manage emotions and behaviors which result from working with others and taking care of patients. How an individual acts and reacts to situations is an aspect of psychology that is rooted in the study of emotion and behaviors which result from emotions. This description serves as the basis for modern analysis of what it means to be emotionally intelligent (EQ). Research suggests that a curriculum which focuses on the development of specific emotional intelligence tenets at certain times in medical and health profession training would help to enhance the development of skill sets associated with EQ. However, before substantial curricular changes are undertaken research specific to PA education is necessary. PMID- 26859901 TI - Returning Evidence at the Appeals Council Level. Final rule. AB - This final rule adopts the notice of proposed rulemaking (NPRM) that we published in the Federal Register on October 21, 2015. This final rule revises our rules regarding returning evidence at the Appeals Council (AC) level. Under this final rule, the AC will no longer return additional evidence it receives when the AC determines the additional evidence does not relate to the period on or before the date of the administrative law judge (ALJ) decision. PMID- 26859902 TI - Schedules of Controlled Substances: Temporary Placement of the Synthetic Cannabinoid MAB-CHMINACA Into Schedule I. Final order. AB - The Administrator of the Drug Enforcement Administration is issuing this final order to temporarily schedule the synthetic cannabinoid N-(1-amino-3,3-dimethyl-1 oxobutan-2-yl)-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (common names, MAB CHMINACA and ADB-CHMINACA), and its optical, positional, and geometric isomers, salts, and salts of isomers into schedule I pursuant to the temporary scheduling provisions of the Controlled Substances Act. This action is based on a finding by the Administrator that the placement of this synthetic cannabinoid into schedule I of the Controlled Substances Act is necessary to avoid an imminent hazard to the public safety. As a result of this order, the regulatory controls and administrative, civil, and criminal sanctions applicable to schedule I controlled substances will be imposed on persons who handle (manufacture, distribute, reverse distribute, import, export, engage in research, conduct instructional activities or chemical analysis, or possess), or propose to handle, MAB-CHMINACA. PMID- 26859903 TI - Reinventing the Wheel: One Program's Approach to Redesign of Didactic Courses. AB - Curriculum and course redesign are expected and intentional efforts in health professions education. For physician assistant (PA) education, ongoing program self-assessment is a required accreditation standard and may guide deliberate changes within curriculum. The purpose of this article is to describe one PA program's approach to the redesign of 4 courses into 3 courses that span the entire didactic phase. Significant lessons learned include the importance of planning ahead, identifying key players, documenting the process as part of ongoing self-assessment, competency mapping, and being prepared to make real-time modifications and changes based on course evaluations and faculty feedback. Our approach and guiding principles to the successful redesign of the didactic courses may provide both established and new PA educational programs with useful methods to apply in their own unique curricula. PMID- 26859904 TI - Schedules of Controlled Substances: Extension of Temporary Placement of PB-22, 5F PB-22, AB-FUBINACA and ADB-PINACA in Schedule I of the Controlled Substances Act. Final order. AB - The Administrator of the Drug Enforcement Administration is issuing this final order to extend the temporary schedule I status of four synthetic cannabinoids pursuant to the temporary scheduling provisions of the Controlled Substances Act. The substances are: quinolin-8-yl 1-pentyl-1H-indole-3-carboxylate (PB-22; QUPIC); quinolin-8-yl 1-(5-fluoropentyl)-1H-indole-3-carboxylate (5-fluoro-PB-22; 5F-PB-22); N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3 carboxamide (AB-FUBINACA); and N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-pentyl 1H-indazole-3-carboxamide (ADB-PINACA), including their optical, positional and geometric isomers, salts, and salts of isomers. The current final order temporarily placing PB-22, 5F-PB-22, AB-FUBINACA, and ADB-PINACA into schedule I is in effect through February 9, 2016. This final order will extend the temporary scheduling of PB-22, 5F-PB-22, AB-FUBINACA, and ADB-PINACA for one year, or until the permanent scheduling action for these four substances is completed, whichever occurs first. PMID- 26859905 TI - Schedules of Controlled Substances: Table of Excluded Nonnarcotic Products: Vicks(r) VapoInhaler(r). AB - This final rule adopts the interim final rule, with a correction to spelling of the manufacturer's name that was published in the Federal Register on October 27, 2015. The Drug Enforcement Administration is amending the table of Excluded Nonnarcotic Products to update the listing for Vicks(r) VapoInhaler(r), containing 50 mg levmetamfetamine in a nasal decongestant inhaler, marketed by The Procter & Gamble Company. This over-the-counter, non-narcotic drug product is excluded from provisions of the Controlled Substances Act. PMID- 26859906 TI - The Changing Landscape of Health Care Coverage and Access: Comparing States' Progress in the ACA's First Year. AB - This analysis compares access to affordable health care across U.S. states after the first year of the Affordable Care Act's major coverage expansions. It finds that in 2014, unin-sured rates for working-age adults declined in nearly every state compared with 2013. There was at least a three-percentage-point decline in 39 states. For children, uninsured rates declined by at least two percentage points in 16 states. The share of adults who said they went without care because of costs decreased by at least two points in 21 states, while the share of at risk adults who had not had a recent checkup declined by that same amount in 11 states. Yet there was little progress in expanding access to dental care for adults, which is not a required insurance benefit under the ACA. Wide variation in insurance coverage and access to care persists, highlighting many opportunities for states to improve. PMID- 26859907 TI - Schedules of Controlled Substances: Table of Excluded Nonnarcotic Products: Nasal Decongestant Inhaler/Vapor Inhaler. Final rule. AB - This final rule adopts, without change, the interim final rule that was published in the Federal Register on October 27, 2015. The Drug Enforcement Administration is amending the table of Excluded Nonnarcotic Products to update the company name for the drug product Nasal Decongestant Inhaler/Vapor Inhaler (containing 50 milligrams levmetamfetamine) to Aphena Pharma Solutions--New York, LLC. This over the-counter, nonnarcotic drug product is excluded from the provisions of the Controlled Substances Act. PMID- 26859908 TI - Foreword. PMID- 26859909 TI - Preface. PMID- 26859910 TI - Calming the Chaos. Disparities and gaps in the treatment of hyperactivity in children has caught some lawmakers' attention. PMID- 26859911 TI - Inhibition of CDK9 prevents mechanical injury-induced inflammation, apoptosis and matrix degradation in cartilage explants. AB - Joint injury often leads to post-traumatic osteoarthritis (PTOA). Acute injury responses to trauma induce production of pro-inflammatory cytokines and catabolic enzymes, which promote chondrocyte apoptosis and degrade cartilage to potentiate PTOA development. Recent studies show that the rate-limiting step for transcriptional activation of injury response genes is controlled by cyclin dependent kinase 9 (CDK9), and thus it is an attractive target for limiting the injury response. Here, we determined the effects of CDK9 inhibition in suppressing the injury response in mechanically-injured cartilage explants. Bovine cartilage explants were injured by a single compressive load of 30 % strain at 100 %/s, and then treated with the CDK9 inhibitor Flavopiridol. To assess acute injury responses, we measured the mRNA expression of pro inflammatory cytokines, catabolic enzymes, and apoptotic genes by RT-PCR, and chondrocyte viability and apoptosis by TUNEL staining. For long-term outcome, cartilage matrix degradation was assessed by soluble glycosaminoglycan release, and by determining the mechanical properties with instantaneous and relaxation moduli. Our data showed CDK9 inhibitor markedly reduced injury-induced inflammatory cytokine and catabolic gene expression. CDK9 inhibitor also attenuated chondrocyte apoptosis and reduced cartilage matrix degradation. Lastly, the mechanical properties of the injured explants were preserved by CDK9 inhibitor. Our results provide a temporal profile connecting the chain of events from mechanical impact, acute injury responses, to the subsequent induction of chondrocyte apoptosis and cartilage matrix deterioration. Thus, CDK9 is a potential disease-modifying agent for injury response after knee trauma to prevent or delay PTOA development. PMID- 26859913 TI - EPIDEMIOLOGICAL SURVEY OF URINARY SCHISTOSOMIASIS IN SOME PRIMARY SCHOOLS IN A NEW FOCUS BEHIND MOUNT CAMEROON, SOUTH WEST REGION, CAMEROON. AB - OBJECTIVE: To Provide baseline epidemiological data (Prevalence, Intensity of Infection and Knowledge) on Urinary Schistosomiasis in a New Focus behind Mount Cameroon. DESIGN: Longitudinal Study. SETTING: Eight (8) Primary Schools in Munyenge Health District, Fako Division, South West Cameroon. SUBJECTS: Six hundred and thirty six (636) randomly selected primary school children aged between five and sixteen years old of both sexes. RESULTS: The overall prevalence of urinary schistosomiasis was 78% with no significant difference (P <= 0.05) between the different sexes. Visible haematuria had a prevalence of 35.1% with the highest prevalence observed in the 9-12-year-age group (87.5%). Response to questionnaires was very poor with only 20.8% of the inhabitants having the knowledge of urinary schistosomiasis. Health--seeking behaviour showed that only 10.4% of infected children had sought treatment of any kind. Prevalence rate and intensity of infection varied significantly with age at P <= 0.05. Also mean egg counts varied significantly with schools (P <= 0.001). CONCLUSION: Munyenge village was identified as a very active focus for Urinary Schistosomiasis with heavy infection rates recorded in the schools closest to the springs. The construction of spring waters has provided suitable habitats for the survival of snails thereby enhancing the effective sustenance of transmission cycle which is capable of leading to further increase and severity of infection. Strengthening of school health programmes related to schistosomiasis in particular is, therefore, advocated. PMID- 26859912 TI - HEALTH RELATED QUALITY OF LIFE OF PATIENTS ON MAINTENANCE HAEMODIALYSIS AT KENYATTA NATIONAL HOSPITAL. AB - BACKGROUND: Health related quality of life is increasingly being recognised as a primary outcome measure in treatment of end-stage renal disease. The health related quality of life of patients on maintenance haemodialysis is reduced. Several interventions directed at modifiable risk factors have been shown to improve quality of life of patients on haemodialysis. OBJECTIVE: To assess the health-related quality of life of patients on maintenance haemodialysis at the Kenyatta National Hospital. DESIGN: Cross sectional descriptive study. SETTING: Kenyatta National Hospital, Renal Unit. SUBJECTS: The study was conducted on 96 patients with end-stage renal disease on maintenance haemodialysis. Socio demographic and clinical factors were recorded for all patients. Health-related quality of life was assessed using the Kidney Disease Quality of Life-36 questionnaire. Two summary scores and three subscale scores were calculated. RESULTS: The mean physical composite summary andmental composite summary scores were 39.09 +/- 9.49 and 41.87 +/- 10.56 respectively. The burden of kidney disease subscale, symptom and problems subscale and effect of kidney disease on daily life subscale scores were 16.15 +/- 21.83, 73.46 +/- 18.061 and 67.63 +/- 23.45 respectively. CONCLUSION: Health-related quality of life of patients on maintenance haemodialysis is reduced. The physical quality of life is more affected than the mental quality of life. The burden of kidney disease subscale is the most affected subscale score. PMID- 26859914 TI - RISK FACTORS FOR HEPATITIS B VIRUS INFECTION DURING PREGNANCY IN SOUTH EASTERN NIGERIA. AB - OBJECTIVE: To determine the seroprevalence of hepatitis B surface antigen (HBsAg) and possible risk factors in pregnant women. DESIGN: A cross-sectional serological survey of women attending antenatal clinics. SETTING: Five antenatal clinics in Aba, South Eastern Nigeria. SUBJECTS: Eight hundred and ten consecutive and consenting antenatal clinic attendees over the period 15 June-15 November 2010. MAIN OUTCOME MEASURES: For each pregnant woman, the medical and sociodemographic data were documented. Hepatitis B surface antigen seropositivity determined. RESULTS: Twenty two (2.7%) of the 810 subjects were found to be HBsAg seropositive and asymptomatic. Maternal age, parity, educational level attained, marital status, history of blood transfusion, intravenous drug use, tattooing, jaundice in the past and Human Immunodeficiency Virus seropositivity did not show any association with HBsAg sseropositivity. CONCLUSION: HBsAg seropositive women in the study were asymptomatic and showed no associationwith the medical and sociodemographic characteristics examined. These findings affirm the recommendation for universal HBsAg screening in pregnancy and imply that screening on the basis of the presence of risk factors alone may be insufficient. PMID- 26859915 TI - NUTRIENT INTAKE AMONG PREGNANT TEENAGE GIRLS ATTENDING ANTE-NATAL CLINICS IN TWO HEALTH FACILITIES IN BUNGOMA SOUTH DISTRICT, WESTERN KENYA. AB - OBJECTIVE: To assess the adequacy of nutrientintake including proteins, energy, calcium, iron, folate and vitamin C and identify the factors associated with nutrient intake. DESIGN: Cross sectional study. SETTING: Healthy facility based. Bungoma District Hospital and Bumula Health centre. SUBJECTS: Teenage pregnant girls attending Antenatal Clinic participated after providing written consent, with girls under 18 years being considered as emancipated minors. A standardised interviewer administered Food Frequency Questionnaire was used to asses the dietary intake. Nutrient calculator was used to determine the nutrient intake of the study participant. RESULTS: The intakes of all selected nutrients were significantly lower than the RDA. Protein intake was significantly associated with Education (OR: 0.537; 95% CI: 0.318-0.907), income (OR: 0.049; 95% CI: 0.919 0.128) and perceived food shortage (OR: 0.617; 95% CI: 0.389-0.890). Energy intake was significantly associated with income (p = 0.007, OR: 2.103; 95%CI: 1.225-3.608). Iron intake was significantly associated with perceived food shortage (OR: 2.548; 95% CI: 1.632-3.980). Hookworm affected calcium intake (OR: 3.074; 95% CI: 1.089-8.698) and malaria parasites affected folate intake (OR: 0.355; 95% CI: 0.226-0.557). Those with hookworm were 3 times more likely to have inadequate calcium intake as compared to those without. CONCLUSION: All the nutrients selected were lower than the Required Dietary Allowance. Level of education, income, Hookworm and malaria affected intake of various nutrients. PMID- 26859916 TI - REGIONAL ANALGESIA FOR POST-OPERATIVE PAIN MANAGEMENT--INITIAL EXPERIENCE IN A LOW RESOURCE SETTING. AB - OBJECTIVE: The aim of this study is to demonstrate the use of some regional anaesthetic techniques in effective postoperative pain control in a low resource setting. We also wanted to find out the potential benefits and prospects of regional techniques to achieve effective postoperative analgesia. DESIGN: This study was a prospective observational study in which 25 patients presenting for various orthopaedic and general surgical procedures were recruited randomly. SETTING: Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria from December, 2008 to May, 2009. SUBJECTS: Eligible patients were males and females aged 21-55 years. These included emergency and elective cases. RESULTS: The age range was 21-55 years with a mean age of 34 years. Of the 25 patient studied, 14 of them were men and 11 women constituting 56% and 44% respectively. Our study shows that Hausa/Fulani ethnic group made up 75% of the study population. Intraoperatively, the anaesthetic techniques used were general anaesthesia (only) in 13 patients (52%), Regional techniques consisting of spinals, epidurals, combined spinals and epidurals and brachial plexus blocks in nine patients (36%) and three (12%) of the patients had a combination of general anaesthesia (GA) and regional anaesthesia (RA). For post-operative pain management, nine patients (36%) had continuous brachial plexus block using intermittent injections, 13 (52%) patients had epidural catheters with intermittent top-up injections and three (12%) patients received combined spinal and epidural with an epidural catheter left in-situ for intermittent top-ups. The drugs used for top-ups included 0.125% plain bupivacaine (15 patients), 0.125% plain bupivacaine + 2.5 mcgs/ml Fentanyl (10 patients) in 10 ml aliquots. The outcome was good in most patients with 19 patients (82.4%) experiencing only mild pain (numeric pain score 0-3). Onset of post-operative pain was 13-18 hours in most (52%) of patients with majority of patients (80%) requiring only a single dose of opioid in 24 hours. There was no incidence of infection at site of catheter insertion one week after the procedure. CONCLUSION: Regional techniques if used properly can provide superior pain control in the post-operative period. There is reduction in the requirements of opioids in the immediate post-operative when regional techniques are used for pain management. We need to encourage the use of these techniques especially in our setting where resources are sparse and potent analgesics are not always available. PMID- 26859917 TI - LITHOPAEDON PRESENTING AS INTESTINAL OBSTRUCTION WITH A PREVIOUS CO-EXISTING INTRA-UTERINE PREGNANCY. AB - This is a case report of a 25 year old lady Para 4 + 0 gravida 5, who was referred to Kisii level 5 hospital from a district hospital with a diagnosis of intestinal obstruction and a four year history of an intra-abdominal mass. A year prior to the admission she conceived and delivered vaginally at home but the baby died a few hours after the delivery. On examination on admission there was a solid mass in the right upper quadrant. Ultrasound imaging showed a poor echo calcified mass suggestive of a colonic metastatic mass and an erect abdominal x ray revealed foetal bones within the abdominal cavity. At laparatomy a lithopedion with a normal uterus was found. The presence of a lithopedion and a normal intra-uterine pregnancy followed by spontaneous vertex delivery has not been reported in Kenya. Patients with lithopaedon can present with intestinal obstruction as a complication but the presence of a co-existing pregnancy is rare. PMID- 26859918 TI - [Antenatal corticosteroids of fetal lung maturation]. PMID- 26859919 TI - [Complications associated with the use of polypropylene mesh in women under colposacropexy]. AB - BACKGROUND: There have been numerous surgical procedures and modi fied in the hope of obtaining a lasting cure for pelvic organ prolapse These surgeries were performed using the traditionally native tissues of the patient. In an effort to reduce morbidity, improve surgical outcomes and reduce the complexity of these operations, we used a growing number of synthetic mesh repairs and biomaterials used tissue from cadaver or animal. OBJECTIVE: To evaluate the frequency of complications associated with the use of polypropylene mesh in women undergoing colposacropexy. MATERIAL AND METHODS: Retrospective, observational and descriptive study conducted at the Hospitalde Ginecologia y Obstetricia 3 IMSS (Mexico) between 1 January 2006 and 15 February 2013. The main risk factors associated with pelvic organ prolapse were considered, comorbidity and complications directly linked to the procedure. RESULTS: With respect to the related complications colposacropexy procedure using polypropylene mesh were documented in 20 of 67 patients which corresponded to 30%. CONCLUSION: A number of complications have been associated with the use of meshes between these include: extrusion, erosion, pelvic pain, dyspareunia, bladder or bowel condition, but one aspect is poorly evaluated sexual dysfunction without to definitely plays an important role in the field bio-psychosocial. PMID- 26859920 TI - [Related factors to lack of implementation of antenatal corticosteroids]. AB - BACKGROUND: Despite the known benefits of antenatal corticosteroids therapy its use in clinical practice is not generalized. OBJECTIVE: To identify factors related to antenatal corticosteroids non administration. METHODS: Cross-sectional and descriptive study that included patients admitted to Hospital Civil de Guadalajara "Dr. Juan I. Menchaca", who had indication for antenatal corticosteroids therapy but did not receive it. Variables: antenatal corticosteroids therapy prescription, factors related to antenatal corticosteroids therapy non administration and lapsed time between diagnosis and birth. RESULTS: Antenatal corticosteroids therapy were not prescribed in 79 (94%) of 84 patients. Main related factors were imminent birth and severe maternal complication. The longer amount of time from diagnosis to birth was before hospitalization (91 vs. 9%, p <0.0005). CONCLUSION: The biggest and best opportunity for the administration of inducers of fetal lung maturity is during prenatal care, when cases with increased risk of preterm birth are detected. PMID- 26859921 TI - [Treatment results for different categories of vaginal intraepithelial neoplasia with electrocoagulation, 5-fluorouracil and combined treatment]. AB - BACKGROUND: Vaginal intraepithelial neoplasia (VAIN) represents a variety of changes that initiate as an intraepithelial squamous lesion with the possibility of resulting in cancer. OBJECTIVE: To compare the results of the treatment for the different categories of VAIN with electrocoagulation, 5-fluorouracil and combined treatment. MATERIALS AND METHODS: Observational an analytical study. We stablished groups according to the category of VAIN evaluating and comparing remission, persistence, recurrence, or progression of the disease ac- cording to the received treatment, with a 1-year follow up. The results were compared by chi2 and Kruskal Wallis. The statistics analysis was done with the SPSS program version 20. RESULTS: One hundred thirty seven patients between 20 and 81 years of age (mean age: 52.49 years) were included. Seventy-four percent of the patients had a history of premalignant or malignant cervical lesions. Seventy-four patients had VAIN I, 34 patients had VAIN II, 22 patients had VAIN III and there were seven cases of vaginal carcinoma in situ. Fifty-eight patients were treated with electrocoagulation, 55 patients were treated with 5-FU, 16 patients had combined treatment, and eight patients received expectant management. Sixty three percent of patients had total remission of the lesion, 34% had persistence and 3% showed progression, and there were no cases of recurrence. Results were better in patients with VAIN I treated with 5-FU (bigger percentage of remission P .026), for the remaining categories of VAIN, no treatment showed superior results. CONCLUSIONS: The superior response occurs in patients with VAIN I treated with 5 FU. None of the treatments achieves a 100% remission. The VAIN frequency is high, patients with a history of malignant or premalignant cervical pathology should undergo a closer surveillance through cytocolposcopic control with respect to the remaining population. PMID- 26859922 TI - [Perinatal outcomes of twin pregnancies conceived through in vitro fertilization versus spontaneous]. AB - OBJECTIVE: Determine maternal and fetal characteristics of in vitro fertilization twin pregnancies in comparison with spontaneous twin pregnancies. MATERIAL AND METHODS: Retrospective historical cohort study between 2011 and 2013. Statistical analysis was performed with SPSS 15.0 program and Epidat 3.0. A value of p<0.05 was considered statistically significant. RESULTS: 96 twin pregnancies met inclusive criteria with an incidence of 2.01%, of which 54.16% were spontaneous twin pregnancies and 45.83% in vitro fertilization twin pregnancies. Mean maternal age at delivery was higher in vitro fertilization twin pregnancies (p=0.004). The primigravidae were more frequent in vitro fertilization twin pregnancies group (p<0.001). Monochorionic pregnancies percentage was superior in spontaneous pregnancies (p=0.009). Amenorrhea at delivery was not a significant difference between cohorts (p=.9). Preterm rate was superior in spontaneous twin pregnancies group (p=0.003). However, "great preterm deliveries" were higher in in vitro fertilization twin pregnancies (p<0.001). Significant differences were not observed in fetal presentation at delivery, first-born child birth-weight or intrauterine growth retardation between the two groups. Nevertheless, the mean birth-weight of second-born spontaneously conceived twins was higher than second born twins of the in vitro fertilization conceived group (p=0.027). Gestational pathology presented the same distribution in both cohorts. There was no significant difference in the mode of delivery between the two groups. Total perinatal mortality rate was 20,83%o and comprised 2 first born twins and 2 second born twins. Three of the stillbirths came from the spontaneous pregnancies group and one from the in vitro fertilization group. CONCLUSIONS: Perinatal death was secondary to stillbirths, which we found higher in spontaneously conceived twin pregnancies due to higher number of monochorionic pregnancies. PMID- 26859923 TI - [Proteomics and PCOS: Is it here the missing link? Literature review]. AB - Polycystic ovary syndrome (PCOS) is known as a common gynecologic and endocrinology disease with multiple short and long-term consequences. It is one of the most common causes for hyperandrogenism and anovulation, increases the risk for metabolic syndrome, type 2 diabetes and cardiovascular disease. Its etiology remains unclear. PCOS is thought to be the result of the interaction between predisposing genetic variants with environmental factors and strongly depends on ethnicity. Proteomics allows the study of several hundreds or thousands of proteins in order to reveal physiological state of a tissue or an organ at the molecular level and to identify disease-specific biomarkers. Its use on PCOS patients will permit us to identify molecules that are involved in the PCOS pathology so we can develop specific diagnostic and management approaches. PMID- 26859924 TI - [Aneurysm of the ascending aorta, hyperthyroidism and pregnancy. Case report]. AB - Aortic aneurysms are a rare condition in childhood and youth, etiology, evolution, natural progression and prognosis in pregnancy unknown. Hyperthyroidism occurs when there is a synthesis and/or excessive secretion of thyroid hormones during pregnancy poses difficulty for diagnosis. The new monitoring hemodynamics in pregnancy by transthoracic bioimpedance is a feasible alternative, noninvasive and real-time hemodynamic monitoring pregnant women. CASE REPORT: Primiparity 18, is referred to present tachycardia, hyperthyroidism is diagnosed and drug treatment is initiated with antithyroid from week 14.1 echocardiogram reports bivalve aortic aneurysm in the sinus of Valsalva is performed. He was determined to continue the same under strict hemodynamic and fetal monitoring. Pregnancy concludes at the end obtained through the abdomen, at 40.4 weeks, with male product, weight 2250 g, Apgar 9/9, with growth restriction type I. The mother and baby were discharged simultaneously without complications. CONCLUSSIONS: The hyperdynamic state of pregnant patients in hyperthyroidism and aneurysms is complex and potentially complicable is why the hemodynamic patient monitoring is essential to detect changes in it that endanger the life of the binomial to this condition. Heart disease and hyperthyroidism, in this case, consistent with a fetal complications level is described as intrauterine growth restriction, however narrow and multidisciplinary monitoring and timely interventions binomial lead to satisfactory results in this case. PMID- 26859925 TI - [Levonorgestrel intrauterine device associated with ureterpyelocaliceal ectasia]. AB - BACKGROUND: In 2010, Health Canada, the equivalent to the FDA, reported that the risk of uterine perforation caused by levonorgestrel intrauterine device (IUD) is very serious, warning that its use had increased the number of uterine perforation. CLINICAL CASE: A 33 years old patient in who was placed three years before a levonorgestrel IUD; She presented evolution of 10 days with pain in hypogastric and both flanks and chronic constipation of two years; in exploration: moderate abdominal distention, IUD strings were not visible in uterine cervix. With translocated IUD diagnosis, a tomography was performed, finding IUD in abdominal cavity and ureter pyelocalyceal bilateral ectasia; preoperative plasma concentration of levonorgestrel 5.1 nmol/L, leukocytosis of 11,000 cells/mm3, and 20-30 erythrocytes in urine exam. Laparoscopic resection of omentum attached to IUD translocated was performed. One month after surgery plasma levonorgestrel in 0.3 nmol/L, normal urinalysis and hematic cytometry and resolution of the urinary tract ectasia. CONCLUSIONS: devices translocated with levonorgestrel, must be removed because the inflammatory reaction caused and the perforation of hollow viscera likelihood, with possibility to produce digestive tract and urinary tract ectasia by its pharmacologic action on smooth muscle. PMID- 26859926 TI - [Repeated ectopic pregnancy in previous caesarean scar: a case report and literature review]. AB - BACKGROUND: Ectopic pregnancy in previous caesarean scar, which is detected in the first trimester, is a recognized and documented today alteration. CLINICAL CASE: Female of 38 years old with a history of five pregnancies (two cesarean sections and three ectopic pregnancies, two EPCSS and one tubal ectopic). In March 2013 she presented the first eight weeks EPCSS diagnosed by transvaginal ultrasound. Gestational sac at the level of the previous cesarean section (CS) over the inner hole and a living embryo were observed. The patient received medical treatment with methotrexate. In March 2014 she was diagnosed with a new tubal ectopic pregnancy which was managed with laparoscopic salpingectomy. In February 2015 (Second EPCSS) she was checked for seven weeks amenorrhea and symptoms of pregnancy. A vaginal ultrasound was performed, finding a gestational sac implanted in the lower uterine segment cesarean scar level and a living embryo. The patient undergoing laparoscopic hysterectomy. CONCLUSION: The recurrent pregnancy caesarean section scar is rare and needs to be properly diagnosed as soon as possible to avoid complications. Transvaginal ultrasound is a suitable tool for diagnosis. Management must be individualized according to patient characteristics. PMID- 26859927 TI - [Vaginal impingement of uterine arteries (Zea technique) prior to cervical curettage in cervical ectopic pregnancy: three case report and literature review]. AB - Cervical ectopic pregnancy is a rare and danger clinical presentation because it has high risk of massive bleeding. The incidence is reported in 1:2500 pregnancies and has high relation with a history of cervical dilatation and curettage and assisted reproductive techniques. Advances in ultrasound resolution and use of beta fraction of human chorionic gonadotropin allow early diagnosis and provide conservative treatment with decreased morbidity, mortality and fertility preservation. Various techniques have been reported associated with cervical curettage, to reduce bleeding at the implantation site. In this report three cases of cervical ectopic pregnancy managed with cervical curettage, prior vaginal impingement of uterine arteries (Zea Technique) at the Instituto Nacional de Perinatologia Isidro Espinosa de los Reyes are described. The Zea technique represents an effective option in the control of obstetric hemorrhage, including patients diagnosed with cervical ectopic pregnancy in who the bleeding volume decrease after its placement. The Zea Technique is easy to apply and preserves fertility. The success of combining this technique with endocervical curettage for the management of cervical ectopic pregnancy is demonstrated. Training for performing this technique does not require highly specialized or highly complex resources since the required material is the usual every area of obstetric care. PMID- 26859928 TI - [Russian Urology in the XXI Century]. PMID- 26859929 TI - [RSU Congress 2015]. PMID- 26859930 TI - [EAU, RSU eye collaborative projects and closer ties]. PMID- 26859931 TI - [VALIDATION OF THE RUSSIAN VERSION OF THE QUESTIONNAIRE TO ASSESS THE EFFECTIVENESS OF SURGICAL TREATMENT OF PATIENTS WITH ANTERIOR URETHRAL STRICTURE (PATIENT-REPORTED OUTCOME MEASURE FOR URETHRAL STRICTURE SURGERY (PROM-USS): A PILOT STUDY]. AB - Currently, the patient-reported outcome measures are widely used for the analysis of the effectiveness of treatment. In 2011, the questionnaire to assess the effectiveness of treatment of men with anterior urethral stricture (PROM-USS) was proposed. Study objective: during validation to perform pilot testing of the Russian version of the PROM-USS questionnaire for determining its psychometric properties (reliability, validity and sensitivity). The study involved 35 men with anterior urethral stricture, who completed PROM-USS questionnaires before and 6 months after surgery. The questionnaire consists of 14 questions and 2 visual analogue scales (VAS), combined in 2 domains: 1--evaluation of lower urinary tract symptoms (LUTS), 2--assessment of the quality of life; questionnaire also includes questions about treatment satisfaction. The reliability, validity and sensitivity of the PROM-USS questionnaire were assessed. High intraclass correlation (ICC) coefficients (0.7-0.96) and Cronbach's alpha = 0.76, indicated reliability of the questionnaire. The correlation coefficient between LUTS scoring and an index of maximum urine flow rate (Qmax)--R = -0.81 (p < 0.05) confirmed the criterion validity. After the surgery, the total LUTS scoring decreased from 14.0 +/- 0.72 to 5.66 +/- 0.58 (P < 0.05); VAS EQ-5D index increased from 51.43 +/- 5.3 to 71.42 +/- 7.64 (P = 0.01) with an increase of Qmax from 3.4 +/- 0.3 to 17.9 +/- 0.9 ml/s (P < 0.001), indicating the sensitivity of questionnaire to changes. Ninety-four percent of men were satisfied and very satisfied with the result of the surgery; 88% had residual LUTS not affecting the quality of life or affecting slightly. For the final conclusions about the feasibility of this tool, further studies involving a larger number of patients are required. PMID- 26859932 TI - [EXPERIENCE OF USE OF BLEMAREN(r) IN THE TREATMENT OF PATIENTS IN URIC ACID AND CALCIUM OXALATE UROLITHIASIS]. AB - 154 patients with urolithiasis were under outpatient observation for 2-8 years. Among them there were 76 women and 78 men aged 21-66 years, of which 46 patients with uric acid urolithiasis, and 88--with calcium oxalate urolithiasis. Treatment of patients was carried out systematically, depending on their condition. Indications for the application of Blemaren(r) included the presence of uric acid stones, uric acid and/or oxalate crystalluria. The duration of treatment was 6.1 months. The dosage of the drug varied from 6 to 18 g per day and was selected individually, depending on the purpose of the appointment of Blemaren(r). Reduction of the urine pH to 6.2- 6.8-7.2 was the criterion for properly selected dose. To dissolve uric acid stones in the presence of hyperuricemia and/or hyperuricuria, Blemaren(r) was administered in combination with allopurinol at a dose of 0.1 g 3-4 times a day. Besides pharmacotherapy, treatment included diet therapy. It was found that the morning urine pH in urate urolithiasis is sustainable and has a range of 5.0-6.0, in 80.4% of cases--range of 5.0-5.5. In calcium oxalate urolithiasis this parameter is also stable and has a range of 5.0 6.7, in 82.9% of cases--range of 5.5-6.0. Optimal urine pH to eliminate uric acid and oxalate crystalluria in patients with uric acid and calcium oxalate urolithiasis is the interval of 6.2-6.4. It was shown that Blemaren(r) is a highly effective agent for treatment and prevention of uric acid and calcium oxalate crystalluria in calcium oxalate and uric acid urolithiasis. Further, its effectiveness in dissolving of uric acid stones in the absence of an infectious inflammatory process is 82.3%. PMID- 26859933 TI - [MARKERS OF KIDNEY DAMAGE AND NEPHROPROTECTIVE THERAPY IN RADICAL CYSTECTOMY]. AB - The comparative analysis of changes of the functional (osmolar clearance and fractional excretion of urea) and structural (NGAL, beta2-microglobulin in the blood plasma, and NGAL, beta2-microglobulin, microalbumin in the urine) biomarkers of kidney damage before and at various stages after radical cystectomy was performed. The study included patients with T2N0M0 stage bladder cancer. The main group consisted of 37 patients receiving nephroprotective treatment (N acetylcysteine), the comparison group--31 patients receiving background therapy. It was revealed that severity of kidney dysfunction and the incidence of chronic kidney disease in the long-term period after surgery decreased in the main group. PMID- 26859934 TI - [SILODOSIN IN THE TREATMENT OF PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA- RESULTS OF RUSSIAN MULTICENTER OBSERVATIONAL STUDY]. AB - The study was aimed to the evaluation of the therapeutic effect of the drug Silodosin at a dose of 8 mg once a day in patients with symptomatic benign prostatic hyperplasia (BPH). This study included 1,000 patients. The average age of the patients was 64.99 +/- 8.07 years (median 64.5 years), mean duration of BPH--3.64 +/- 5.058 years (median 1.1 years). Such a large scatter is due to the enormous heterogeneity of the data; in such cases, it is advisable to focus on the median value. 12 (1.2%) patients discontinued study early, 4 of them due to adverse drug reactions, 1 patient withdrew informed consent, 7 patients were lost to follow up. Among comorbidities, cardiovascular diseases and cerebrovascular disease had the highest frequency--both in 39 (3.9%) patients. The frequency of other preexisting disease did not reach 3%. According to the history of cases, urinary retention occurred in 115 (11.5%) patients, urinary tract infections--in 131 (13.1%), prostatitis--in 171 (17.1%), abnormal ejaculation--55 (5.5%), erectile dysfunction--in 103 (10.3%). The primary efficacy variable was the change of total IPSS score. At visit 1, the average total score was 19.29 +/- 5.93, at visit 2 (4 weeks)--13.30 +/- 5.31 (P < 0.001), at visit 3 (8 weeks)- 9.80 +/- 4.95 (P < 0.001), at last available to the observation visit--9.84 +/- 4.90, and the change was statistically significant compared with baseline score (P < 0.001). The study revealed the positive dynamics of lower urinary tract symptoms, as well as positive changes in the assessment of quality of life. Thus, at the time of the last available observation, the QoL score was 1.93 +/- 1.03 points against 4.25 points at visit 1 and was statistically significant (P < 0.001). During the study, 12 (1.2%) patients had 13 adverse events, and doctors associated 11 of them with taking the drug (silodosin); information on relation with any drug was absent in 2 of 13 cases. PMID- 26859935 TI - [DIAGNOSIS AND TREATMENT OF OVERACTIVE BLADDER SYNDROME IN PELVIC INJURIES]. AB - Case records of 1994 patients with injuries of the pelvic ring were analyzed. The article presents the results of examination and treatment of patients with urinary tract dysfunction. A frequent complications of pelvic fractures include overactive bladder syndrome (OAB) (18.9%). Many factors play a role in the development of this syndrome, in particular damage to the pelvic diaphragm and the development of pelvic hematoma. OAB is more common in unstable pelvic fractures (24.8%). Surgical stabilization of the pelvic ring injuries and the use of M-cholinoblockers and a1-blockers lead to a reduction of OAB. PMID- 26859936 TI - [ASSESSMENT OF THE RISK OF INCIDENTAL PROSTATE CANCER PROGRESSION]. AB - At present, methodology based on the stage T1a or T1b is used to determine the risk of incidental prostate cancer (IPC) progression. This approach was developed before the introduction of prostate-specific antigen (PSA) into the practice of the urologist, and does not account of the degree of IPC. For the prediction of IPC progression, multifactorial prognostic model was created. This model is based on the analysis of two parameters--the total PSA level before the surgery and the Gleason score according to the results of morphological examination after transurethral resection of the prostate hyperplasia. This model has a high predictive value (AUC 86.6%) and can be easily used in practice. For the interpretation of the calculated results special table is formed that allows to assess the risk of progression over the next 3.5 years. PMID- 26859937 TI - [PCA3 AND TMPRSS2:ERG GENES EXPRESSION IN BIOPSIES OF BENIGN PROSTATE HYPERPLASIA, INTRAEPITHELIAL NEOPLASIA, AND PROSTATE CANCER]. AB - Morphological analysis of the biopsies for prostate cancer (PCa) often is a difficult task due to heterogeneity and multifocality of tumors. At the same time, a lot of data exist about the potential molecular genetic markers of PCa. The aim of our study is to determine of PCA3 and TMPRSS2:ERG genes expression in benign hyperplasia (BPH), low and high grade intraepithelial neoplasia (PIN), PCa for revealing of diagnostic value of those genes expression in benign and precancerous changes in prostate. Total RNA was isolated from 53 biopsies, reverse transcription was performed, gene expression was determined by real time PCR (RT-PCR) then deltaCt index was determined as Ct(PCA3)--Ct(KLK3). Average deltaCt and its SD in BPH were 8.28 +/- 3.13, low PIN--8.56 +/- 2.64, high PIN- 8.98 +/-1.69, PCa--1.08 +/- 2.36. We have demonstarted that deltaCt did not differ in patients with BPH, low and high grade PIN, whereas significantly increased in PCa relative to any of the three groups listed above (p < 0.0001). Expression of TMPRSS2:ERG was absent in BPH, PIN, but it was detected in 40% (4/10) of PCa cases. ROC-analysis showed that the AUC (area under ROC-curve with 95% CI, p < 0.0001) was 0.98 +/- 0.02 in the analysis of a combination of overexpression of PCA3 and TMPRSS2:ERG. Thus, the expression analysis of the PCA3 and chimeric oncogene TMPRSS2:ERG in biopsy cannot be used for differential diagnosis of BPH, low and high grade PIN. However, overexpression of PCA3 and expression of TMPRSS2:ERG are characteristic in PCa. Expression analysis of these genes by the proposed RT-PCR modification at the threshold level deltaCt 3,22 has diagnostic accuracy 90% to detect PCa in biopsy specimens. PMID- 26859938 TI - [THE CONTROL OF BLEEDING FROM THE LUMEN OF THE ISOLATED INFERIOR VENA CAVA SEGMENT WHEN REMOVING THE TUMOR THROMBUS]. AB - The paper analyzes surgical methods of bleeding control from the lumen of the isolated inferior vena cava (IVC) segment during thrombectomy. The study included 13 patients with IVC tumor thrombus. The sources of bleeding were divided into variant lumbar veins and lumbar veins of the infrarenal IVC segment. Variant lumbar veins were classified as vessels entering IVC at its posterior surface at suprarenal level. The volume of blood loss from the lumen of the isolated IVC segment during thrombectomy ranged from 100 to 3500 ml with an average of 507.3 ml. The main sources of bleeding were lumbar veins of the infrarenal IVC segment, located at a distance of less than 10 mm from the mouth of the right renal vein (85.7%). Variant veins were found much rarer--in 35.7% of cases. Their orifice diameter and, consequently, the blood loss volume was significantly smaller than those in the group of bleeding from infrarenal lumbar vessels. In 2 (15.4%) cases, the mouths of the venous tributaries were stitched inside the vena cava. In 6 (46.2%) patients the bleeding was stopped by applying a clamp to lumbar veins following the blood clot removal. This maneuver proved successful in 4 (66.7%) of those cases. In the remaining 5 (38.5%) cases, the bleeding was stopped by compression of probable variant or lumbar vein mouth localization with finger or cotton swab. If unable to stop bleeding in the described way, the blood from IVC lumen was evacuated by suction, and cavatomy was closed as quickly as possible. Given the low effectiveness, high complexity and risk of the available methods of IVC lumen bleeding control, visual information about the location and the number of possible sources of bleeding should be obtained preoperatively. PMID- 26859939 TI - [NARROWED SPECTRUM DIAGNOSTICS AND COMPUTER CHROMOENDOSCOPY IN THE DIAGNOSIS OF EPITHELIAL NEOPLASMS OF THE LOWER AND UPPER URINARY TRACT]. AB - Tumors of epithelial origin occupy the first place in the structure of oncological diseases. This study was aimed to the evaluation of the possibilities of narrowed spectrum endoscopy and computer chromoendoscopy in the diagnosis of epithelial structures of the bladder and upper urinary tract. MATERIALS AND METHODS: Additional diagnostic endoscopic examination of the lower urinary tract was performed in 76 patients (132 urethrocystoscopies). For the evaluation of the efficacy of complementary technologies in the endoscopic examination of the upper urinary tract, 47 patients were examined (57 endoscopic examinations of UUT). RESULTS: During endoscopic examination of the bladder only in the "white light", 80 suspicious lesions were identified and removed. The additional use of NBI- diagnosis allowed to reveale and remove 9 (9.5%), abnormal structures, 6 of them (66.7%) were representatives of transitional cell carcinoma. The additional use of a computer chromoendoscopy revealed 6 (6.3%) neoplasms missed during endoscopy in white light: 4 samples (66.7%) were transitional cell carcinoma, 1 (16.7%)- squamous papilloma. Endoscopic examination of the upper urinary tract only in the "white light" identified and removed 47 suspicious lesions. Additional application of narrowed spectrum regimenhas allowed to identify and remove 8 (12.9%) pathological lesions, 3 (37.5%) of which were morphologically transitional cell carcinoma. The additional use of a computer chromoendoscopy indentified 7 (11.3%) tumors missed during endoscopy of UUT in "white light", 4 (57.1%) of which were transitional cell carcinoma. All other biopsies obtained were representatives of chronic inflammation, or material was not suitable for morphological examination. CONCLUSIONS: Our experience of the use of narrowed spectrum diagnostics and computer chromoendoscopy allowed to improve the diagnosis of bladder cancer by 14.3%, and to improve the detection of transitional cell carcinoma of the upper urinary tract by 14.9% at the stage of development of the method. PMID- 26859940 TI - [PARAMETERS OF SPERMATOGENESIS IN MEN EXPOSED TO DIFFICULT ENVIRONMENTS]. AB - This study was aimed to the comparison of the effects of various unfavorable factors on spermatogenesis and the level of free radical oxidation in the ejaculate. 40 men of reproductive age who visited doctor for lack of children within 2-3 years of marriage were examined. Patients were divided into 4 groups depending on the action of the unfavorable factors: the oil and gas industry workers, workers of radio-location and television and radio broadcasting facilities, creative workers, the unemployed and low-income people. The control group consisted of physically healthy men of similar age who had children within marriage. The malondialdehyde levels in the ejaculate and morphokinetic parameters of sperm cells were assessed. Natural gas and oil-dissolved gas were the most toxic against fertilizing properties of the ejaculate, they led to sharp decline in sperm concentration and motility of sperm cells by reducing the active mobile forms in oil and gas industry workers. In workers of radio-location and television and radio broadcasting facilities, essential modifications of sperm cell morphology were caused by mechanical damage of the microwave radiation. In creative workers suppression of spermatogenesis had complex nature due to the enhanced dynamics of free-radical oxidation, as well as the participation of the central regulatory mechanisms. The unemployed and low-income people with hyponutrition and malnutrition had suppression of spermatogenesis caused by a lack of biological resources necessary to maintain spermatogenesis and provide reliable antioxidant protection. There was an increase in the dynamics of aging of sperm cells. Thus, the intensity of lipid peroxidation, as well as the nature and direction of specific unfavorable factor determine the cumulative effect of the toxicity of this factor and the fertilizing capacity of the ejaculate. PMID- 26859941 TI - [FEATURES OF CLINICAL COURSE AND MORPHOMETRIC PARAMETERS OF BENIGN PROSTATIC HYPERPLASIA IN MEN WITH METABOLIC SYNDROME AND ANDROGEN DEFICIENCY]. AB - The study was aimed to the evaluation of the effect of the components of the metabolic syndrome (obesity, insulin resistance (IR)) and androgen deficiency on the clinical course of lower urinary tract symptoms against the background of benign prostatic hyperplasia (LUTS/BPH) and nocturia, as well as on some of the parameters of BPH (prostate volume, residual urine volume, total prostate specific antigen (PSA) blood level). The comprehensive survey of 160 men with LUTS/BPH (mean age 56.7 +/- 3.3 years) was performed; based on the results of survey, three comparison groups were formed: Group 1 (n = 70)--patients with isolated obesity; Group 2 (n = 36)--patients with obesity and insulin resistance; and Group 3 (n = 54)--patients with obesity, insulin resistance and androgen deficiency. The control group consisted of 30 patients with LUTS/BPH without these metabolic and hormonal disorders. In patients with LUTS/BPH and obesity, higher frequency of nocturia compared with the control group was revealed (63.7% vs 23.3%; P < 0.05), as well as the relationship between the waist circumference and free testosterone level (n = 160; r = -0.322; P = 0.005) and waist circumference and total prostate volume (n = 160; r = 0.121; P = 0.005). In patients of Group 2, significant positive correlation between waist circumference and blood insulin level was identified (n = 36; r = 0.461; P = 0.005). Patients with obesity, insulin resistance and androgen deficiency had the highest average prostate volume and residual urine volume compared with those of other groups (P < 0.05). Thus, obesity, insulin resistance, androgen deficiency are associated pathological conditions, greatly aggravating the clinical course of LUTS/BPH due to adverse impact on the BPH parameters, acting both together and separately. The most severe LUTS/BPH were associated with the presence of all three of the above systemic disorders. PMID- 26859942 TI - [ROLE OF CYTOMEDINES IN THE TREATMENT OF PATIENTS WITH CHRONIC PROSTATITIS ASSOCIATED WITH IMPAIRED SPERMATOGENESIS]. AB - The efficiency and safety of tablet drug Vitaprost in the treatment of 35 patients with chronic abacterial prostatitis associated with impaired spermatogenesis were evaluated. The treatment course comprises the use of drug 1 tablet 2 times a day for 60 days. It was shown that Vitaprost had a positive effect on the basic parameters of spermatogenesis, helping to increase the number of sperm cells (28.8%), their mobility (17%), and viability (14.2%). The number of abnormal sperm cells at the same time decreased by 26.2%. PMID- 26859943 TI - [HYPERBARIC OXYGEN THERAPY IN THE TREATMENT OF MALE INFERTILITY ASSOCIATED WITH INCREASED SPERM DNA FRAGMENTATION AND REACTIVE OXYGEN SPECIES IN SEMEN]. AB - The aim of this study was to explore the potential of hyperbaric oxygenation (HBO) for reduction of sperm DNA fragmentation level and reactive oxygen species (ROS) in semen. The study included 90 men with idiopathic infertility. Patients of the treatment group (n = 60) underwent HBO before the vitro fertilization (IVF) procedure. In the control group (n = 30) IVF was carried out without prior cours of HBO. Sperm DNA fragmentation analysis was carried out using the TUNEL assay, the level of ROS in the ejaculate was measured by chemiluminescence. HBO treatment resulted in a significant decrease in the mean level of sperm DNA fragmentation from 33.2 +/- 7.5 to 11.9 +/- 5.9%, and the median ROS in sperm from 0.89 to 0.39 mV/s (p < 0.05). In the control group these changes were not statistically significant. Pregnancy after IVF occurred in 63.3% (38/60) of sexual partners of the treatment group men and in 36.7% (11/30) of the control group (p < 0.05). The high efficiency of HBO in overcoming the adverse effects of oxidative stress on sperm parameters allows us to consider it as a promising method for the treatment of men with idiopathic infertility. PMID- 26859944 TI - [DELAYED PORT DEPLOYMENT FOR HAND-ASSISTED LAPAROSCOPIC DONOR NEPHRECTOMY. CASE REPORT AND LITERATURE REVIEW]. AB - The standard method of surgical treatment of end-stage renal failure is kidney transplantation. A laparoscopic method of organ retrieval from a living donor is currently preferred. The techniques of laparoscopic surgery include hand-assisted nephrectomy and "pure" laparoscopic nephrectomy. We present analysis of the literature data and our own data on the use of the advantages of each of the techniques. A case of complication associated with the use of hand-port from our own practice is described. PMID- 26859946 TI - [FIRST EXPERIENCE OF ENTEROPLASTY OF EXTENDED URETHRAL STRICTURE. CLINICAL CASE]. AB - Restoration ofpatency ofthe upper urinary tract in the extended lesions is a complex urological problems whose solution can significantly improve the quality of life of patients, and allows to avoid patient's disability. In the urological department of regional clinical hospital, for the first time we performed the plastic reconstruction of the left ureter for its extended (7 cm) stricture using segment of ileum, with good results in the early postoperative period. Restoration of the natural passage ofurine allows to hope for a good functional outcome in the long-term period. PMID- 26859945 TI - [RARE CASE OF STOMACH CANCER METASTASIS]. AB - The article presents the description of the case of metastasis of stomach cancer in the right testicle and epididymis, cellular tissue along the spermatic cord, prepuce and scrotum in the absence of metastases in the peritoneum and abdominal organs. PMID- 26859947 TI - [DIAGNOSIS OF METABOLIC DISORDERS AND METAPHYLAXIS OF RECURRENT CALCIUM OXALATE UROLITHIASIS]. AB - The paper presents the results of the 1-year screening of biochemical parameters of urine in female patient with recurrent calcium urate urolithiasis. Based on the data of quantitative X-ray phase analysis of the composition of stone and a complex of clinical and laboratory examination, reasons for recurrent stone formation were determined. The main reasons included hypocitraturia, hyperosmolarity of urine and uric acid diathesis. Therapy with citrate mixtures and adequate water schedule (daily urine--2-2.5 liters) for 10 weeks allowed to increase the urinary pH, led to 2.5-fold increase in daily urinary citrate excretion and getting rid of residual stones in both kidneys. The effect of citrate therapy lasted for a further six months after drug withdrawal. Subsequently, the daily urinary citrate excretion and pH decreased, but even after 8 months remained still above baseline values. Obviously, for high risk patients it is necessary to define the daily excretion of citrate, and diagnosis of hypocitraturia requires long course therapy with citrate mixtures, with a break ofnot more than six months and obligate maintenance of adequate diuresis. PMID- 26859948 TI - [OPTION OF THE TRANSPLANT URINARY TRACT RECONSTRUCTION WITH RECIPIENT'S OWN URETER IN CASE OF THE RENAL TRANSPLANT PATHOLOGY]. AB - This article describes an extremely rare case of reconstruction of allograft ureteropelvic junction by ureter of contralateral kidney. The authors present a concise literature review of this pathology treatment options. PMID- 26859949 TI - [RENAL ECHINOCOCCOSIS]. AB - The article summarizes data on the prevalence, clinical manifestations, diagnosis and treatment of renal echinococcosis. The clinical observation of the disease lasted for 10 years is presented. At the beginning, the character of the small (1.5 x 2 cm) renal cyst was difficult to determine. And lack of case follow-up led to the pronounced renal injury, which required the nephrectomy. PMID- 26859950 TI - [THE MODERN VIEW OF CONSERVATIVE THERAPY OF LOWER URINARY TRACT SYMPTOMS IN MEN]. AB - This literature review summarizes recent evidence on monotherapy and combined treatment of lower urinary tract symptoms in men with benign prostatic hyperplasia. Particular attention is given to the latest publications on this topic presented at the 30th Congress of the European Association of Urology. alpha-blockers, 5alpha-reductase inhibitors, anticholinergics and phosphodiesterase type 5 inhibitors are the main classes of medications for monotherapy. Combination therapy of the above medications is the most promising part of this trend in urology allowing increase the effectiveness of treatment of lower urinary tract symptoms due to benign prostatic hyperplasia. A personalized approach to therapy involves a thorough examination of the patient and the administration of treatment according to his individual needs. PMID- 26859951 TI - [REPRODUCTIVE DYSFUNCTION AS A RESULT OF INFECTIOUS AND INFLAMMATORY DISEASES]. AB - Tuberculosis remains an important medical and socio-demographic problem. Chronic inflammation of the prostate gland--of both non- specific and tuberculous etiology--reduces the quality of the ejaculate; this in the initial low level of fertility in a population can have dramatic effects. Infertility can be the first symptom prompting the patient to visit a doctor; and patient is diagnosed with tuberculosis after survey. However, the influence of tuberculosis of the prostate on the functional parameters of ejaculate has not been studied. The positive influence of selenium and zinc preparations on the quality of the ejaculate in patients with chronic nonspecific prostatitis, idiopathic infertility was demonstrated, but the effectiveness of their complex use in tuberculosis of the prostate gland has not been studied. PMID- 26859952 TI - [MIRABEGRON. WHETHER WILL BE A REVOLUTION IN THE PHARMACOTHERAPY OF OVERACTIVE BLADDER?]. AB - This article provides an overview of the current state of the problem of effective pharmacotherapy for overactive bladder (OAB). The review presents standard pharmacotherapy and a new stage in the treatment of OAB--innovative drug Mirabegron. International and domestic studies confirmed high and predominant in many respects efficacy of mirabegron and a good safety profile. Conducted at the Research Institute of Urology own research demonstrated no influence on the quality of the bladder emptying, which proves the urodynamics safety. Taking into account the efficacy of mirabegron for all OAB symptoms, proven in a Randomized Clinical Tials (RCT), mirabegron has big potential and is able to make a revolution in the pharmacotherapy of OAB. PMID- 26859953 TI - [OPTIMAL APPROACH TO COMBINED TREATMENT OF PATIENTS WITH UROGENITAL PAPILLOMATOSIS]. AB - The review analyzed 59 sources of domestic and foreign literature on the use of immunomodulator izoprinozin in treating patients infected with human papilloma virus, and the results of their own experience. The high prevalence of HPV and its role in the development of cervical cancer are shown, the mechanisms of HPV development and the host protection from this infection are described. The authors present approaches to the treatment of HPV-infected patients with particular attention to izoprinozin. Isoprinosine belongs to immunomodulators with antiviral activity. It inhibits the replication of viral DNA and RNA by binding to cell ribosomes and changing their stereochemical structure. HPV infection, especially in the early stages, may be successfully cured till the complete elimination of the virus. Inosine Pranobex (izoprinozin) having dual action and the most abundant evidence base, may be recognized as the optimal treatment option. PMID- 26859954 TI - [DIAGNOSIS OF UROGENITAL TUBERCULOSIS]. AB - The sequential algorithm of diagnosis of tuberculosis of the urogenital system with emphasis on the identification of the causative agent is presented; the approach to the examination of the patient is described in detail; regimens of ex juvantibus treatment are provided. PMID- 26859955 TI - [The Bach Institute of Biochemistry celebrates its 80th Anniversary]. PMID- 26859956 TI - [Enzymatic Synthesis of Acidic beta-Lactams (Review)]. AB - The currently known methods of enzymatic beta-lactam synthesis, as well as the enzymes and heterogeneous biocatalysts used for this purpose, are presented, and the published reports on advances in the field of enzymatic synthesis of selected antibiotics belonging to the groups of acidic penicillins and acidic cephalosporins are summarized in the present review. The key conditions and parameters of biocatalytic processes, such as the biocatalyst form, concentration of the precursor compounds, solvent type, pH, temperature, etc. are analyzed and compared, and guidelines for further optimization of beta-lactam synthesis are given. The present review may be of use for a wide range of readers, as well as to enzymology and biotechnology experts. PMID- 26859957 TI - [Structural and Functional Organization of the Signal Peptide of ProEnterotoxin B from Staphylococcus aureus]. AB - A series of genes of proenterotoxin B from Staphylococcus aureus containing signal peptide mutant forms was constructed in order to study the functional roles of the introduced mutations. It was shown that a continuous mutation in the n-region of the signal peptide does not affect the secretion efficiency of proenterotoxin B, in contrast to the analogous mutation in the h-region. Point mutations of the proprotein signal peptide, including the N-terminal amino-acid residue of the mature protein, were obtained. It was shown that the introduced structural. changes cause a decrease in secretion efficiency and a redistribution of the protein in various compartments of Escherichia coli cells. PMID- 26859958 TI - [Redox Status of Extremophilic Yeast Yarrowia Lipolytica During Adaptation to pH Stress]. AB - In this study we investigated the activities of antioxidant enzymes (superoxide dismutases (SODs) and catalases (CATs)) and the ROS level in cells of Yarrowia lipolytica yeasts grown in a medium with different pH values (4.5, 5.5 and 9.0). It was shown that an increase in the cellular ROS level took place under both acid and alkaline conditions. The growth under extreme conditions was accompanied by a significant increase of SOD activity (by 2.5 times in the acid medium and by 4 times in the alkaline medium), but catalase activity did not change. A study of the electrophoretic profile of catalases showed the presence of three isoforms differing in inhibitor resistance. The electrophoretic profiles of SODs and their inhibitory analysis revealed there are two other isoforms, probably of mitochondrial origin, in addition to Cu and Zn SOD. The role of SOD in pH adaptation of extremophilic Y. lipolytica yeasts is discussed. PMID- 26859959 TI - [Influence of Oxygenated Derivatives of Linoleic and Linolenic Acids on the Formation of Conidia and Protoperithecia in Wild-Type and Photoreceptor Complex Mutants of Neurospora crassa]. AB - The regulatory effect of two oxyderivatives of unsaturated fatty acids (oxylipins), 18-hydroxy-(9Z,12Z)-octadecadienoic acid (18-HODE) and 18 (9Z,12Z,15Z)-octadecatrienoic acid (18-HOTrE), on the sexual and asexual sporulation of wild-type Neurospora crassa strains and wc-1 and wc-1 mutants was studied. In the wild-type strain, 18-HODE, unlike 18-HOTrE, stimulated protoperithecia formation in the dark and in the light. In the same strain, the studied oxylipins influenced conidiagenesis only under illumination. 18-HODE stimulated and 18-HOTrE inhibited the conidia formation. Oxylipins had no effect on protoperithecia formation in photoreceptor complex mutants, which apparently indicated its involvement in signal transmission in N. crassa. The stimulating action of the studied oxylipins on conidiagenesis in wc-1 and the lack of action in wc-2 may indicate alternative signaling pathways of oxylipins in this process. PMID- 26859960 TI - [A New Enzyme Preparation with High Penicillopepsin Activity Based on the Producer Strain Penicillium canescens]. AB - The producer of fungal penicillopepsin, an aspartate protease, has been created by genetic engineering. The biochemical and physicochemical properties of the penicillopepsin enzyme preparation obtained from the culture liquid of the producer were studied. Properties of the new enzyme preparation and the commercially available aspergillopepsin were compared. Their proteolytic activities were found to be 670-680 U/g of the preparation. The soluble protein yield upon the wheat flour hydrolysis with penicillopepsin was 2.7 times higher than with aspergillopepsin. It is probably caused by the presence of the xylanase activity in the penicillopepsin preparation. PMID- 26859961 TI - [Use of Endoglucanase IV from Trichoderma reesei to Enhance the Hydrolytic Activity of a Cellulase Complex from the Fungus Penicillium verruculosum]. AB - The effect of polysaccharide monooxygenase (endoglucanase IV) from the fungus Trichoderma reesei on the hydrolysis of polysaccharide substrates by cellulases secreted by the fungus Penicillium verruculosum has been investigated. Supplementation of the enzyme complex from P. verruculosum by endoglucanase IV from T. reesei has been shown to elevate the efficiency of cellulose hydrolysis by 45%. PMID- 26859962 TI - [New Virulent Bacteriophages Active against Multiresistant Pseudomonas aeruginosa Strains]. AB - The sensitivity of 512 newly isolated Pseudomonas aeruginosa clinical strains to six classes of anti-microbial preparations has been studied. Antibiotic-resistant strains were selected and genotyped. Three new virulent bacteriophages of the families Myoviridae and Podoviridae were isolated against these strains. The parameters of the intracellular phage development cycle were established, and the influence of inactivating factors (temperature, pH, and UV exposure) on phage viability was studied. The molecular weight of the phage genome was determined. Phage DNA restriction analysis and polyacrylamide gel electrophoresis in the presence of envelope protein SDS were carried out. The plating efficacy of phages on 28 genetically distant antibiotic-resistant P. aeruginosa strains was studied. It was established that 26 of them were lysed by phages with a high efficacy. The range of antibacterial action of the studied phages and their mixtures on 427 multi-drug-resistant clinical isolates was assessed. It is shown that including these phages in one multicomponent preparation enhanced their lytic activity. PMID- 26859963 TI - [Influence of Polycations on Antibacterial Activity of Lysostaphin]. AB - The synergistic antibacterial activity of lysostaphin and polycations of different chemical structures against Staphylococcus aureus has been shown. Polycations improved the lytic activity of lysostaphin against the peptidoglycan of staphylococci. It is proposed that this resulted in decreased binding of positively charged lysostaphin with S. aureus cell-wall teichoic acids. These data provide an opportunity to search for polycations that would amplify the synergistic effect of lysostaphin or other antibacterial proteins against staphylococci. PMID- 26859964 TI - [Immunochromatographic Test System for the Detection of T-2 Toxin]. AB - An immunochromatographic test system was developed for the detection of T-2 toxin (T2T), which is one of priority contaminants of cereals. The detection is based on the competition between T2T in the sample and the T2T-protein conjugate immobilized on the test strip for the binding to the complexes of anti-T2T antibodies with gold nanoparticles serving as the marker. The results of the competition are recorded as the coloration in the test zone of the test strip produced by the marker. The optimum dilution of the sample for the reliable high sensitivity analysis corresponds to the final methanol concentration equal to 20%. The deceleration of the movement of reactants along the test strip due to the use of additional membranes impregnated with 10% BSA resulted in the decrease in the detection limit of T2T. The test system was examined for the detection of T2T in water-methanol extracts of maize grains. The disappearance of the color in the test zone, which attests to the presence of mycotoxin, was observed for grain samples containing T2T at a concentration of 53 MUg/kg or more (the final T2T concentration in the immunochromatorgaphic assay is 3 ng/mL). The video-digital detection limit of T2T is 16 MUg/kg (0.9 ng/mL). The duration of the assay is 15 min. The results of the present study suggest that the developed test system is suitable for the control of the maximum allowable T2T content. PMID- 26859965 TI - [Artificial Inversion of the Left-Right Visceral Asymmetry in Vertebrates: Conceptual Approaches and Experimental Solutions]. AB - Externally, vertebrates are bilaterally symmetrical; however, left-right asymmetry is observed in the structure of their internal organs and systems of organs (circulatory, digestive, and respiratory). In addition to the asymmetry of internal organs (visceral), there is also functional (i.e., asymmetrical functioning of organs on the left and right sides of the body) and behavioral asymmetry. The question of a possible association between different types of asymmetry is still open. The study of the mechanisms of such association, in addition to the fundamental interest, has important applications for biomedicine, primarily for the understanding of the brain functioning in health and disease and for the development of methods of treatment of certain mental diseases, such as schizophrenia and autism, for which the disturbance of left-right asymmetry of the brain was shown. To study the deep association between different types of asymmetry, it is necessary to obtain adequate animal models (primarily animals with inverted visceral organs, situs inversus totalis). There are two main possible approaches to obtaining such model organisms: mutagenesis followed by selection of mutant strains with mutations in the genes that affect the formation of the left-right visceral asymmetry and experimental obtaining of animals with inverted internal organs. This review focuses on the second approach. We describe the theoretical models for establishing left-right asymmetry and possible experimental approaches to obtaining animals with inverted internal organs. PMID- 26859966 TI - [On the Features of Embryonic Cleavage in Diverse Fish Species]. AB - Literature on the earliest steps of fish embryogenesis (including a number of "non-model" species) has been considered. The main attention has been paid to the loss of cleavage division synchrony and the first latitudinal cleavage furrow. In teleostean embryos, the features of their meroblastic cleavage are not rigidly associated with egg size. The midblastula transition (in a form clearly enough) occurs in some chondrostean and teleostean fishes, but it has not been detected in the representatives of sarcopterygian and chondrichthyan fishes. PMID- 26859967 TI - [Fertility and Embryonic Mortality Level of the Japanese Mitten Crab Eriocheir japonica (Crustacea: Decapoda: Varunidae) in Primorye]. AB - Reproductive biology of the Japanese mitten crab Eriocheir japonica (de Haan, 1835) was studied in the northern part of its habitat. It was revealed that E. japonica from the water bodies of Primorye, in contrast to crabs in the central part of the habitat on the Japanese Islands, lays fewer eggs in the first clutch, does not have direct dependence between the size-weight characteristics of females and the number of eggs in the third clutch, and shows higher level of embryonic mortality. The loss of eggs during the embryonic period in each of three sequentially laid clutches was 16, 34, and 52%, respectively (28% in total during the period of reproduction). Fecundity was approximately 43%. It was registered that the specifics of reproductive biology of E. japonica (monocyclicity, prolonged period of reproduction, portion spawning, indirect embryonic development, high fertility, relatively small and yolk enriched eggs, pelagic planktotrophic larva, high level of energy costs on reproduction, egg bearing on the pleopods, high level of embryonic mortality), an intermediate strategist, is in a good agreement with its life strategy, thereby enabling this species to realize its reproductive potential in the northern part of the habitat. PMID- 26859968 TI - [Increased Size of Epidermal Cells in Syringa josikaea Jacq. Smaller Leaf Side as an Adaptive Mechanism for Reducing Its Asymmetry]. AB - Comparative study of quantitative anatomy of the epidermis in Syringa josikaea Jacq. leaf halves of different width was conducted in order to analyze the possible mechanism of formation of the value of fluctuating leaf asymmetry. A regular decrease in the density of main epidermal cells in the smaller leaf half compared with the bigger one was traced during leaf ontogeny. Stomatal index was equal in different-sized leaf halves. Adaptive response was found in fully formed leaves; it was aimed at reducing leaf blade fluctuating asymmetry by 23% on average and consisted of compensatory growth--further elongation of main epidermal cells in the smaller half of the leaf. It was concluded that the level of fluctuating leaf asymmetry in Hungary lilac is mainly due to a lower rate of cell division, as well as due to their greater elongation in the smaller half of adult leaf compared with the bigger half. PMID- 26859969 TI - [Evaluation of Indicators of Postejaculation Maturation of Spermatozoa of Bos taurus Using a Chlortetracycline Test]. AB - Postejaculation maturation of spermatozoa (capacitation and acrosomal exocytosis) in bovine sperm was assessed using the method of staining with chlortetracycline and inhibitor analysis to identify the transition ways of calcium of intracellular depots under the influence of highly dispersed silica. It was shown that highly dispersed silica in a concentration of 0.001% stimulates capacitation but has no impact on the acrosome exocytosis in bovine sperm. Activated by highly dispersed silica, capacitation was inhibited in the presence of cytochalasin D and H-89 inhibitors, whereas nocodazole and Ro 31-8220 had no influence on this process. The joint action of theophylline and guanosine diphosphate stimulates an increase in the amount of capacitated sperm cells, similarly to highly dispersed silica; inhibitors cytochalasin D and H-89 restrict the capacitation of sperm activated by these compounds. At the same time, the joint effect of prolactin and guanosine triphosphate had no effect on the capacitation of spermatozoa; addition of nocodazole and Ro 31-8220 inhibitors did not alter the effect of prolactin and guanosine triphosphate on the capacitation of sperm. A hypothesis was put forward, according to which increase in the cryoresistance of spermatozoa of bulls under the influence of highly dispersed silica is, apparently, determined by the transition of Ca2+ between the intracellular stores in the direction from inositol triphosphate-sensitive to inositol triphosphate-insensitive intracellular stores of calcium. The obtained data allow us to expand the notion of the biochemical mechanisms of capacitation in the spermatozoa of bulls. PMID- 26859970 TI - [Influence of the Concentration of Dissolved Oxygen on Embryonic Development of the Common Toad (Bufo bufo)]. AB - Several series of experiments investigating the influence of dissolved oxygen concentrations on the growth rates and mortality in the embryogenesis of the common toad Bufo bufo were carried out. The experiments showed that, when the eggs develop singly, the lack of oxygen does not lead to an increase in mortality by the time of hatching and results only in a change in the dynamics of mortality: mortality occurs at an earlier stage of development than in the conditions of normal access to oxygen. Taking into account the combined effect of the density of eggs and the dissolved oxygen concentration, we increase the accuracy of analysis of the experimental results and improve the interpretation of the results. In the conditions of different initial density of eggs, the impact of the concentration of dissolved oxygen on mortality and rates of development of the common toad embryos is manifested in different ways. At high density, only a small percentage of embryos survives by the time of hatching, and the embryos are significantly behind in their development compared with the individuals that developed in normal oxygen conditions. The lack of oxygen dissolved in the water slows down the development of embryos of the common toad. PMID- 26859971 TI - [Research of Embryonic Mortality Stages of Drosophila melanogaster Depending on Age and Starvation of an Imago]. AB - Influence of age of parents and duration of starvation on egg production and demonstration of embryonic mortality at different stages of egg development has been studied. It is shown that, with increasing age of organisms, the overall egg production reduces and the percentage of embryonic mortality increases at 0-5.5 and 5.5-17 h of development. An increase in the duration of starvation also promotes a reduction in egg production in 3- and 10-day-old adult D. melanogaster compared with short-term starvation. A statistically significant effect of factors, such as the allelic state of the white locus, the genetic background, the age of the parents, and the duration of starvation, on all studied parameters was established. PMID- 26859972 TI - [Coordination of governmental and public control in providing sanitary epidemiologic well-being of population and consumers' rights protection]. AB - The article covers features of govenmental and public control in providing sanitary epidemiologic well-being of population and consumers' rights protection. Based on analysis of contemporary legislation, the authors evaluated terms "control" and "supervision", having different legal nature. The authors determined specific traits and define subjects and objects for public control in relationships aimed to provide sanitary epidemiologic well-being of population, evaluated legislative basis of citizens' claims to Rospotrebnadzor, pointed at difficulties in implementation of public control in connection with necessity to create new organizational and legal mechanisms widening control possibilities. PMID- 26859973 TI - [Ultrasound examination in diagnosis and classification of occupational myofibrosis (lecture)]. AB - Based on comparative analysis of contemporary clinical and instrumental investigations, the authors justify advantage of ultrasound examination in diagnosis of occupational myofibrosis. Results of ultrasound application helped to specify a classification of occupational myofibrosis according to the disease severity, that considerably increases efficiency of examining connection between the disease and occupation. PMID- 26859974 TI - [Evaluating dependency of medical rehabilitation results in occupational polyneuropathy patiens on treatment strategy and work conditions]. AB - The authors evaluated efficiency of rehabilitation in patients with upper limbs occupational polyneuropathy, in accordance with length of service under physical overstrain. The study was based on follow-up of 268 patients. Treatment was initiated after the patients discontinued work hazardous for health. Drug and sanatorium treatment was effective in 67-86% of patients (with differences in occupational groups). The effect was only transitory (for 15-60 days) decrease of the disease clinical manifestations. Rehabilitation prognosis was reliably better in patients who worked during the disease development in conditions with number of stereotypic working movements of hands within hygienic norms. The treatment efficiency is reliably higher when started at younger age, regular drug and sanatorium treatment for many years. Placement of the patients on jobs avoiding physical overstrain enabled nowadays to prevent progression of occupational polyneuropathy. PMID- 26859975 TI - [Dynamics of blood gases and acid-base balance in patients with carbon monoxide acute poisoning]. AB - Evaluation of blood gases and acid-base balance covered patients with carbon monoxide acute poisoning, in accordance with inhalation trauma presence. Evidence is that thermochemical injury of respiratory tract induced severe acid-base dysbalance remaining decompensated for a long time despite the treatment. PMID- 26859976 TI - [Characteristics of pain syndrome in patients with upper limbs occupational polyneuropathies]. AB - Pain syndrome accompanies various diseases of central and peripheral nervous system--that is one of the most important problems in contemporary neurology. Many scientists are in search for effective diagnostic and therapeutic tools. The article covers characteristics of the pain syndrome and its mechanisms in patients with upper limbs occupational polyneuropathies. PMID- 26859977 TI - [Objective evaluation of rehabilitation efficiency in patients with upper limbs occupational vegetosensory polyneuropathy]. AB - Clinical and neurophysiologic study covered efficiency of rehabilitation in 40 patients with upper limbs occupational vegetative-sensory polyneuropathy. Each patient underwent infrared thermography and electroneuromyography of hands before and after the treatment. Findings are that post-treatment nerve impulse velocity in right median nerve has improved considerably, thermovisual pictures of both upper limbs also have reliably improved. Electroneuromyography and infrared thermography for evaluation of rehabilitation efficiency are justified. Applied rehabilitation protocol was clinically effective, reliable improvement in the patients state was registered. PMID- 26859979 TI - [Indicators and criteria of the assessment of quality of medical examinations of workers]. AB - The results of periodic medical examinations (PME) of workers of the machine building enterprise are analyzed and factors defining their quality are considered. The criteria of PME quality are proposed and used along with analysis of the defects of medical records. With help of Pareto chart the most significant factors affecting the quality of PME are revealed. These were noted in 76% of cases and included: lack of expertise of fitness to work, the discrepancy of the results of this expertise and the worker's pathology, the lack of registration and collection of complaints and anamnesis. PMID- 26859978 TI - [Evaluating health risk caused by exposure to metals in local foods and drinkable water in Pechenga district of Murmansk region]. AB - Total average daily intake of metals with local food by natives equalled: Cu 2%, Pb 6%, Cd 22%, Hg 40%, Ni 66%, As 157%--in comparison with allowable daily intake. Mushrooms are responsible for total intake of 35% Pb, 55% Cu, 61% Ni and 91% Cd; fish gives 83% Hg and 75% As. The natives' exposure to Ni is caused by mushrooms, wild and cultivated berries and vegetables, exposure to Cd--by mushrooms, that to Hg--by freshwater fish, exposure to As--by salmon and cod. Drinkable water contribution into exposure to metals is negligibly small for Hg, Cd, Pb and Cu, mild for As and considerable for Ni (23%). Total carcinogenous risk with Cu and Pb are negligible, with Cd is 0.22, with Hg 0.39, with Ni 0.81, with As 1.62, with totality of metals for total foods and water--3.1. Total carcinogenous risks with Pb are minimal (less than 10(-6)), with Cd--allowable (less than 10(-5)), with As--average (less than 10(-3)), with Ni--high (10(-2)), with totality of metals for total foods and water--1.25 x 10(-2). Increased health risks revealed necessitate recommendations on reduction/exclusion of some local foods intake by the natives and measures on drinkable water purification from nickel, or usage of other sources of clear water. PMID- 26859981 TI - [Influence of smoking and industrial air pollutants on respiratory health of nickel industry workers]. AB - Studies covered respiratory health of 1530 workers of nickel industry, among which were 796 (52.0%) smokers. Findings are that tobacco smoke combined with nickel industry hazards cause potentized negative effects in respiratory organs, with earlier and more frequent chronic bronchitis. For isolated influence of these factors, chronic bronchitis risk is higher from exposure to tobacco smoke vs. occupational hazards (OR = 2.48; DI 1.49-4.13). Chronic obstructive lung disease development in nickel industry workers is caused by smoking. Industrial air pollutants appeared to have no potentizing effect on COLD formation, as well as on toxic pneumosclerosis formation. PMID- 26859980 TI - [Efficiency of periodic medical examinations of medical staffers in Volgograd]. AB - The authors analysed management and quality of periodic medical examinations among medical staffers of medical establishments of Volgograd city and suggested organizational measures to improve efficiency and quality of periodic medical examinations. PMID- 26859982 TI - [Results of "Occupation and health" XIII Russian congress with international participation]. PMID- 26859983 TI - [To the memory of Nonna Vladimirovna Dogle]. PMID- 26859985 TI - [Spatio-Temporal Bioelectrical Brain Activity Organization during Reading Syntagmatic and Paradigmatic Collocations by Students with Different Foreign Language Proficiency]. AB - Texts or words/pseudowords are often used as stimuli for human verbal activity research. Our study pays attention to decoding processes of grammatical constructions consisted of two-three words--collocations. Russian and English collocation sets without any narrative were presented to Russian-speaking students with different English language skill. Stimulus material had two types of collocations: paradigmatic and syntagmatic. 30 students (average age--20.4 +/- 0.22) took part in the study, they were divided into two equal groups depending on their English language skill (linguists/nonlinguists). During reading brain bioelectrical activity of cortex has been registered from 12 electrodes in alfa-, beta-, theta-bands. Coherent function reflecting cooperation of different cortical areas during reading collocations has been analyzed. Increase of interhemispheric and diagonal connections while reading collocations in different languages in the group of students with low knowledge of foreign language testifies of importance of functional cooperation between the hemispheres. It has been found out that brain bioelectrical activity of students with good foreign language knowledge during reading of all collocation types in Russian and English is characterized by economization of nervous substrate resources compared to nonlinguists. Selective activation of certain cortical areas has also been observed (depending on the grammatical construction type) in nonlinguists group that is probably related to special decoding system which processes presented stimuli. Reading Russian paradigmatic constructions by nonlinguists entailed increase between left cortical areas, reading of English syntagmatic collocations -between right ones. PMID- 26859984 TI - [Changes in Spatial Organization of Cortical Rhythm Vibrations in Children uner the Influence of Music]. AB - Changes is systemic brain activity under influence of classical music (minor and major music) were studied at two groups of healthy children aged 5-6 years (n = 53). In 25 of studied children the Luscher test showed increased level of anxiety which significantly decreased after music therapy sessions. Bioelectrical cortical activity registered from 20 unipolar leads was subjected to correlation, coherence and factor analysis. Also the dynamics of the power spectrum for each of the EEG was studied. According to EEG all children after listening to both minor and major tones showed reorganization of brain rhythm structure accompanied by a decrease in the level of coherence and correlation of EEG; also was found significant and almost universal decrease in the EEG power spectrum. Registered EEG changes under the influence of classical music seems to reflect a decrease in excess of "internal tension" and weakening degree of "stiffness" to ensure the activity of cerebral structures responsible for mechanisms of "basic integration" which maintain constant readiness of brain to rapid and complete inclusion in action. PMID- 26859986 TI - [Investigation of the Reactivity of the Mu Rhythm during Observation, Auditory Perception and Movement Imitation: Correlation with Empathic Ability]. AB - The purpose of this work was to study the reactivity of EEG mu-rhythm during observation, auditory perception and imitation of circular hand movements with a computer mouse, and its correlation with empathic ability of an individual. During observation of hand movements, we discovered a significant desynchronization of the mu rhythm in the hemisphere contralateral to the observed hand (electrode C3; a decrease by 6.9%). During auditory perception of the sounds of computer mouse movements (with eyes closed), we observed a significant decrease in the amplitude of the mu rhythm under electrodes C(z) (6.7%) and C3 (4.4%). During movement imitation, we discovered a decrease in the amplitude of the mu rhythm under electrodes C(z) (12.6%), C3 (23.2%) and C4 (16.7%). The result of self-assessment of empathic ability by the Questionnaire of Emotional Empathy of Mehrabian and Epstein was positively correlated (r = 0.47) with the averaged values of desynchronization of the mu rthythm under three central electrodes during auditory perception; during observation and imitation, no significant correlations were found. We suggest that empatic ability is more likely to correlate with the activity of "logically related" mirror neurons, than with that of "strictly congruent" ones. PMID- 26859987 TI - [Dynamics of EEG Alpha-Activity and Heart Rate Variability in Subjects Performing Cognitive Tests]. AB - Changes in the power and coherence of alpha-activity and heart rate variability (HRV) were studied in students with different performance levels in logical tasks. In those students who reached high scores in the cognitive tests, we observed higher lability of alpha-activity and HRV; the values and their ratios varied among the stages of intellectual activity. In these subjects, a decrease in the spectral power of alpha-band was more pronounced than in other groups. We also observed changes in the interhemispheric coherence and in the structure of coherent interactions in the alpha-range at different stages of task performance. In contrast, the number and structure of coherent interactions in individuals who showed lower results did not significantly vary at different stages of task performance. As compared with this group, the students with higher test results showed a more pronounced decrease in the total spectral power (TP) and an increase in the low frequency/high frequency (LF/HF) ratio which returned to the initial level after the end of the tests. In students with better results in these cognitive tests, the dynamics of RRNN, TP, HF, and LF/H F during task performance correlated with the dynamics of interhemispherical alpha-band coherence. PMID- 26859988 TI - [Sex Differences in Visual Task Switching (an fMRI Study)]. AB - Executive functions are an important ability of human brain to program, regulate and control various cognitive processes; one of these processes is the voluntary task switching. However, the sex differences in this process are poorly studied. In our study, these differences were investigated in 70 healthy subjects (36 men and 34 women) aged 21-48 years by means of functional magnetic resonance imaging (fMRI) and neuropsychological examination. During the fM RI study, the subjects had to shift their attention between two tasks (classifying figures according to their form or number). During neuropsychological examination, the subjects completed a series of visual attention, task switching and memory tests. The results of fMRI study showed that visual task switching in women is carried out by a neuronal network, consisting of dorsolateral prefrontal cortex, inferior parietal areas, secondary visual areas of both hemispheres and cerebellum cortex. Task switching in men involved the same areas and, in addition, right supplementary motor area, right insula and left thalamus. As compared with women, the rate of activation of prefrontal cortex, left parietal lobe and right insula in men was significantly higher. The results of neuropsychological tests showed that men completed the tasks with attention switching, searching and arranging of stimuli significantly slower than women. The data demonstrate the differences in the organization of task switching processes in men and women. PMID- 26859989 TI - [The Development of Clinical and Morphological Manifestations of Chronic Alcoholic Myopathy in Men with Prolonged Alcohol Intoxication]. AB - Chronic alcoholic myopathy occurs in 40-60% of patients who abuse alcohol, and is accompanied by decreased performance, proximal paresis and atrophy of skeletal muscles. However, it is unknown what is important in the development of the disease: duration of alcohol abuse, or the dose of ethanol consumed. Unknown dynamics of the pathological process in skeletal muscle. We examined male patients identified with alcoholic myopathy and without it, evaluated the duration of alcohol abuse, intake of ethanol, morphological characteristics m.quadriceps vastus lateralis and the content of IGF-1 in plasma. It has been shown that chronic alcoholic myopathy develops after 10 years of alcohol abuse; proximal paresis is observed only in patients with atrophy of muscle fibers, thus there is a transformation of myosin phenotype from slow to fast. The decrease IGF 1 in plasma detected at the early stages of the Church, including in patients without clinical manifestations of proximal paresis and morphological signs of atrophy of muscle fibers. PMID- 26859990 TI - [Memorization of Sequences of Movements of the Right and the Left Hand by Right- and Left-Handers]. AB - We analyzed the errors of right- and left-handers when performing memorized sequences by the left or the right hand during the task which activates positional coding: after 6-10 times the order of movements changed (the positions remained the same during all task). The task was first performed by one ("initial") hand, and then by another one ("continuing"); there were 2 groups of right-handers and 2 groups of left-handers. It was found that the pattern of errors during the task performance by the initial hand is similar in right- and left-handers both for the dominant and non-dominant hand. The information about the previous positions after changing the order of elements is used in the sequences for subdominant hands and not used in the sequences for dominant ones. After changing the hand, right- and left-handers show different patterns of errors ("non-symmetrical"). Thus, the errors of right- and left-handers are "symmetrical" at the early stages of task performance, while the transfer of this motor skill in right-and left-handers occurs in different ways. PMID- 26859991 TI - THE EFFECT OF MATURITY ON HEART RATE RESPONSES DURING TRAINING AND TESTING IN POSTPUBESCENT FEMALE VOLLEYBALL PLAYERS. AB - The aim of this study was to examine the effect of maturity, assessed as difference between chronological age and age at peak height velocity, on heart rate (HR) responses to maximal and submaximal laboratory and field exercises. Twenty-eight postpubescent female volleyball players participated in the present study (age 13.8 (0.6) yr, body mass 62.5 (8.2) kg and height 1.73 (0.05) m; mean (standard deviation)). They were divided into two groups with regards to their maturation: less matured (LM) and more matured (MM). In laboratory, HR was recorded during 5 min rest, physical working capacity in heart rate 170 bpm, 3 min step test, 30 s Bosco test and Wingate anaerobic test (WAnT) were performed. In field, a 70 min training session (consisted by three parts: warm-up, 1 x 1 drills and team drills) was monitored and 20 m shuttle run endurance test was performed. There was significant difference between LM and MM groups over HR responses (%HR reserve, %HRR) to exercise training (F(2,21) = 6.08, p = 0.008, eta2 = 0.37). There was a main effect of part session of exercise program on HR responses with the highest intensity recorded in 1 x 1 drills (-75% HRR) and the lowest in team drills (-60% HRR in LM and -65% HRR in MM). There was also a moderate effect of maturity on HR during cycling against 90 W and in the WAnT, and small effect on HR during cycling against 60 W, in the end of the step test, Bosco test and running endurance test, where the highest scores were recorded in LM. Based on the findings of the present study, it was concluded that maturity exerted an effect of small to moderate magnitude on H R responses in a laboratory setting and this should be taken into account by coaches and trainers when evaluating physiological characteristics. PMID- 26859992 TI - [Age Peculiarities of Formation of Spinal Inhibition of Skeletal Muscle in Males]. AB - Age peculiarities of spinal inhibition in males in the relative muscular rest condition were studied. The main stages of development and formation processes of spinal inhibition in males, and set periods of weakening and increasing during ontogeny. It's shown, that the development and formation of different types of spinal inhibition in the period from 9 to 18 years there heterochronically and definitive level of their development are on a different age: presynaptic inhibition of heteronymous Ia afferent and reciprocal inhibition homonymous alpha motoreurons in the age of 9-12 years, recurrent inhibition of heteronymous alpha motorneurons--17-18 years, and nonreciprocal inhibition of heteronymous and homonymous alpha-motorneurons--14-15 years. Teenage age is a critical period in the development of presynaptic inhibition heteronymous and homonymous Ia afferents, recurrent inhibition alpha-motorneurons. Discusses the physiological mechanisms underlying the observed age-specific patterns. PMID- 26859993 TI - [Functional Status of Microcirculatory-Tissue Systems during the Cold Pressor Test]. AB - Using non-invasive optical methods of laser Doppler flowmetry, tissue reflectance oximetry and pulse oximetry, we investigated the dynamics of parameter changes of microcirculatory-tissue systems (MTS) when using cold pressor test (CPT) on 32 conventionally healthy volunteers. According to differences in the recovery rate of oxygen consumption during CPT, volunteers can be conditionally divided into 2 groups: 1--displaying normal physiology and 2--with a tendency to angiospasm and lack of functional recovery of the MTS. To identify possible causes of angiospasm, we performed a detailed analysis of blood flow oscillations. This analysis revealed that the cause of angiospasm may be a violation of the tone shaping myogenic mechanisms regulating resistive microvessels, disturbances to the microcirculation of stagnant blood, or a combination of both of these factors. Use of the CPT for functional assessment of MTS allows us not only to estimate the reserve capabilities of the MTS, but also to identify--at a pre clinical stage-propensity to angiospasm, which has practical value in the clinic. PMID- 26859994 TI - [Interrelations between Electrodermal Activity and Internal Diseases]. AB - The article deals with a new medical technhique for the assessment of autonomic regulation of internal systems and skin. We suggest investigating skin sympathetic nervous activity by the method of electrodermal testing of skin sympathetic reactions. It has been showed that current of 200-250 microamperes and 12 volts is optimal for testing the skin sympathetic responses in adult patients. We observed 12 groups of patients with various diseases and a control group of apparently healthy people. Each of the experimental groups consisted of people with severe or moderately severe pathology of a certain type of visceral system which caused significant functional or structural disorders in the tissue of some organ. The study carried out on distal extremities revealed 12 pairs of skin segments of vegetative support; we suggested a conception of vegetotome--a site of embryonic development of the autonomic nervous system, which provides single autonomic innervation of individual sections of meso-, ento- and ectoderm. PMID- 26859995 TI - [Early Stages of Parkinson's Disease: Comparative Characteristics of Sleep Wakefulness Cycle in Patients and Model Animals]. AB - The results of study of sleep-wakefulness cycle in experimental models of pre clinical and early clinical stages of Parkinson's disease present and compared to some clinical examples. The conclusion is, the increase in activity level and decrease in total amount of slow wave and paradoxical sleep in model animals are taking place at the same circadian period of the secretion of pineal melatonin as sleep disorders in patients. PMID- 26859996 TI - [Nonlinear Parameters of the Surface Electromyogram for the Diagnostics of Neuromuscular Disorders and Normal Conditions of the Motor System in Human]. AB - The article presents data on new approaches to the application of the surface electromyogram based on the nonlinear dynamics of complex systems. Special focus is placed on applicability of nonlinear parameters for early and differential diagnostics of Parkinson's disease, various kinds of tremor, schizophrenia, as well as for the estimation of normal processes in the motor system, such as musle development, fatigue and ageing. PMID- 26859997 TI - [Endurance and Fatigue Caused by Local Muscular Performance in Skilled Athletes]. AB - It was the objective of this research to study the functional parameters of endurance and performance and the brain electrobiological activity during local antebrachial muscle work performance among skilled athletes and unfit people aged 18-23. We examined performance and the brain bioelectrical activity changes at local muscle work by means of an ergograph until fatigue. Our results suggested that local performance increased the spectral power of slow alpha- and theta waves as the fatigue set in, but these changes developed slower and were manifested later in the athletes than in the unfit people. Besides, tired athletes' EEGs showed alpha waves synchronization and only demonstrated a decrease in low- and high frequency beta waves indexes. Athletes show higher performance and lower fatigability if compared to unfit people during local performance, also proved by the EEG bioelectrical changes. PMID- 26859998 TI - [The Pulvinar of the Cat: Structural and Functional Organization and the Role in Cognitive Processes]. AB - The present review is devoted to modern knowledge about a structure and function of the cat's lateral posterior-pulvinar complex of the thalamus (LP-P). The LP-P is a subcortical structure belonging to visual system. This complex appears in phylogenesis simultaneously with lateral geniculate body and visual cortex, develops structurally and in human, occupies about 1/3 of the thalamus. The LP-P is a so-called associative nucleus of the thalamus and it is anatomically and functionally complex structure. The complex has reciprocal connections with many cortical areas and may participate in the regulation of a flow of visual information to the cortex modulating cortical processes. The function of the LP-P is still not fully understood. Experimental data allows to believe that this complex participate in such cognitive processes as attention and orienting to visual stimuli, in visually-guided behavior and spatial coding of visual stimuli as well as in binding of particular features of visual objects in the whole percept and maybe in the processes of short-term memory during analysis of visual stimuli. PMID- 26859999 TI - [Serotonergic Control of Aggressive Behavior: Novel Approaches--New Interpretations (Review)]. AB - The concept of a major inhibitory role of serotonin in aggressive behavior is widely accepted by researchers. There were ample evidences that a pharmacologically-induced increase in serotonergic activity attenuates agonistic behavior, and the manipulations inhibiting the brain serotonergic system can elicit aggressiveness in animals. Ealier, experimental studies have demonstrated reduced metabolism in brain serotonergic system and specific changes in pharmacological sensitivity of 5-HT(1A) receptors in male mice with repeated experience of aggression. It has been shown that mRNA levels of the serotonergic genes in the midbrain raphe nuclei are reduced in aggressive males. After no fight period expression of some genes is restored or becomes higher compared with the controls on the background of increased aggression. The review provides data supporting and contradicting the serotonin-deficiency hypothesis of increased aggressiveness, revealing non-specific role of serotonin in the control of aggressive behavior, and also provides information about the inhibition of serotonergic activity under repeated experience of aggression. PMID- 26860000 TI - [Extinction and Reconsolidation of Memory]. AB - Retrieval of memory followed by reconsolidation can strengthen a memory, while retrieval followed by extinction results in a decrease of memory performance due to weakening of existing memory or formation of a competing memory. In our study we analyzed the behavior and responses of identified neurons involved in the network underlying aversive learning in terrestrial snail Helix, and made an attempt to describe the conditions in which the retrieval of memory leads either to extinction or reconsolidation. In the network underlying the withdrawal behavior, sensory neurons, premotor interneurons, motor neurons, and modulatory for this network serotonergic neurons are identified and recordings from representatives of these groups were made before and after aversive learning. In the network underlying feeding behavior, the premotor modulatory serotonergic interneurons and motor neurons involved in motor program of feeding are identified. Analysis of changes in neural activity after aversive learning showed that modulatory neurons of feeding behavior do not demonstrate any changes (sometimes a decrease of responses to food was observed), while responses to food in withdrawal behavior premotor interneurons changed qualitatively, from under threshold EPSPs to spike discharges. Using a specific for serotonergic neurons neurotoxin 5,7-DiHT it was shown previously that the serotonergic system is necessary for the aversive learning, but is not necessary for maintenance and retrieval of this memory. These results suggest that the serotonergic neurons that are necessary as part of a reinforcement for developing the associative changes in the network may be not necessary for the retrieval of memory. The hypothesis presented in this review concerns the activity of the "reinforcement" serotonergic neurons that is suggested to be the gate condition for the choice between extinction/reconsolidation triggered by memory retrieval: if these serotonergic neurons do not respond during the retrieval due to adaptation, habituation, changes in environment, etc., then we will observe the extinction; while if these neurons respond to the CS during memory retrieval, we will observe the reconsolidation phenomenon. PMID- 26860001 TI - [Topography of the Event-Related Brain Responses during Discrimination of Auditory Motion in Humans]. AB - The present study investigates the hemispheric asymmetry of auditory event related potentials (ERPs) and mismatch negativity (MMN) during passive discrimination of the moving sound stimuli presented according to the oddball paradigm. The sound movement to the left/right from the head midline was produced by linear changes of the interaural time delay (ITD). It was found that the right hemispheric N1 and P2 responses were more prominent than the left-hemispheric ones, especially in the fronto-lateral region. On the contrary, N250 and MMN responses demonstrated contralateral dominance in the fronto-lateral and fronto medial regions. Direction of sound motion had no significant effect on the ERP or MMN topography. The right-hemispheric asymmetry of N1 increased with sound velocity. Maximal asymmetry of P2 was obtained with short stimulus trajectories. The contralateral bias of N250 and MMN increased with the spatial difference between standard and deviant stimuli. The results showed different type of hemispheric asymmetry for the early and late ERP components which could reflect the activity of distinct neural populations involved in the sensory and cognitive processing of the auditory input. PMID- 26860002 TI - [Electroencephalograpic Parameters of Healthy Persons with Different Successfulness of Dual-Task Performance (Postural Control and Calculation)]. AB - Complex electroencephalographic (EEG), stabilographic and psychological study was executed during the number dual tasks performance--postural control and calculation in 25 healthy volunteers (age 25 +/- 0.7). Successful performances of dual tasks required a high usage of cognitive resources, such as memory and attention as well as good motor command and low level of anxiety. Two EEG-markers of successful dual tasks performance were revealed. An increase of EEG coherence for long diagonal pairs of leads between frontal and parieto-occipital areas was observed. Additionally a decrease of EEG coherence for short pairs of leads was revealed. The poor performance of dual tasks was accompanied by an increase of EEG coherence between local pairs of leads for different spectral bands. PMID- 26860003 TI - [Brain Bioelectrical Activity in Early Childhood Specific for Children Living in Orphanages]. AB - We investigated whether the electroencephalogram (EEG) during visual fixation in institutionalized children shows the altered oscillation properties. EEG was recorded in the "eyes open" situation with visual attention fixed on a cartoon in 51 2-3.5 years old children living in Simferopol orphanage, Crimea and in 53 age matched children living in families. Oscillation properties were measured using the relative power (RP) indices of theta-, alpha-, beta- and gamma-rhythms. Institutionalized children showed higher RP of alpha rhythm in seven loci (frontal polar, anterior temporal, posterior temporal and left occipital derivations), lower RP of theta rhythm in eight loci (frontal polar, frontal, anterior temporal and posterior temporal derivations). In addition, RP of beta- and gamma-rhythms were decreased in the left anterior temporal area. These results suggest that institutionalized children show impaired development of CNS, in particular development of limbic system and neocortex, probably are caused by early social deprivation. PMID- 26860004 TI - [Electrographic Correlations of Inner Speech]. AB - On the purpose to detect in EEG specific patterns associated with any verbal performance the gamma activity were investigated. The technique which allows the subject to initiate the mental pronunciation of words and phrases (inner speech) was created. Wavelet analysis of EEG has been experimentally demonstrated that the preparation and implementation stages are related to the specific spatio temporal patterns in frequency range 64-68 Hz. Sustainable reproduction and efficient identification of such patterns can solve the fundamentally problem of alphabet control commands formation for Brain Computer Interface and Brain to Braine Interface systems. PMID- 26860005 TI - [Correlation between Sensory Gating P50, Mismatch Negativity, and Reaction Time]. AB - This paper is about the correlation pre-attentive processes, such as P50 sensory gating (SG P50) and mismatch negativity (MMN) with each other and with sensorimotor reaction time (RT). SG P50 data were obtained in the standard paired click paradigm, MMN was measured in the passive odd-ball paradigm sensorimotor reaction time was studied in an active odd-ball paradigm. Was obtained positive correlation sensory gating P50 with amplitude mismatch negativity, amplitude mismatch negativity with sensorimotor reaction time, sensory gating P50 with sensorimotor reaction time. PMID- 26860006 TI - [Dependence of Accuracy of Automatic Sleep Scoring on Spectral Characteristics of Mice EEG]. AB - Computer programs for automatic sleep scoring of human and animals EEG records are widely used in many branches of physiological research. They are particularly useful during the sleep research because the traditional methods requiring human expert scoring of long records are very laborious and time-consuming. The aim of this work was to investigate the dependency of accuracy of automatic sleep scoring on different EEG parameters for EEG-recording quality assessment. We find statistically significant dependency of accuracy of automatic and expert scoring on several spectral characteristics. This dependency can be used as objective quality assessment method of EEG recording for sleep scoring and it makes possible to assess accuracy of automatic sleep scoring a priori. PMID- 26860007 TI - Five Reasons Your Dental Practice Should be Using Google AdWords. PMID- 26860008 TI - Morphometric Analysis in the Diagnosis of Low-Grade Ductal and Lobular Carcinoma in Situ of the Breast. AB - OBJECTIVE: To identify quantitative histological features that can differentiate between low grade ductal carcinoma in situ (LG-DCIS) and classic type lobular carcinoma in situ (C-LCIS). STUDY DESIGN: Regions of solid intraductal proliferation from scanned hematoxylin and eosin images of LG-DCIS (20 cases) and C-LCIS (25 cases) were analyzed using Mercator Version 1.0 (ExploraNova, La Rochelle, France). The system detects structures based on optical density. Multiple variables were measured, including estimators of size (mean nuclear area), shape (form factor), and staining (grayscale value). We also calculated the percentage that nuclei, cytoplasm, and white space represent in the total gland surface area. RESULTS: C-LCIS showed higher mean nuclear area, higher percentage of nuclear area, higher nuclear and cytoplasmic grayscale values, and lower percentage of cytoplasm area as compared to LG-DCIS. Combination of these variables using a random forest learning algorithm classified correctly 80% of LG DCIS cases and 69% of C-LCIS cases. CONCLUSION: Morphometric analysis is potentially a useful ancillary tool in the distinction between low-grade ductal and lobular in situ proliferations of the breast. PMID- 26860009 TI - Noninvasive Tumor Grading of Glioblastomas Before Surgery Using Arterial Spin Labeling. A Cohort Study. AB - OBJECTIVE: To assess the clinical value of using arterial spin labeling (ASL) technique preoperatively for non-invasive tumor grading in glioblastoma (GBM) patients. STUDY DESIGN: Forty-nine patients with GBMs were selected, including 21 patients with high-grade gliomas and 28 patients with low-grade gliomas. ASL perfusion imaging was performed with GE Signa Excite HD 3.0 T MR scanning system (GE Healthcare). Relative cerebral blood flow (rCBF) and relative tumor blood flow (rTBF) were quantified in all patients. Statistical analysis was performed with STATA version 12.0 software. Further, relevant human cohort studies published in Chinese and English languages were identified by database searches and screened. Data was extracted and meta-analysis was performed using Comprehensive Meta-analysis version 2.0 software. RESULTS: The ratios of rTBF to rCBF in the contralateral white matter, contralateral gray matter, and contralateral hemisphere of high-grade gliomas were higher than low-grade gliomas (all p < 0.05). ASL results in the solid tumors revealed that rCBF was greater in high-grade gliomas. Such differences in rCBF were not significant (p > 0.05) when 2 and 5 cm distances from tumor margin were compared. Importantly, rCBF values showed statistical differences when the 2 cm distance was compared with the 5 cm distance from tumor margin (all p < 0.05). Finally, meta-analysis results supported the conclusion that rCBF and rTBF values were significantly higher in high-grade GBM as compared to low-grade GBM. CONCLUSION: We present convincing data that ASL is highly effective in differentiating between high-grade and low grade gliomas, and thus is a useful tool for preoperative evaluation of GBM. PMID- 26860010 TI - Evaluation of Cytogenetic and Genotoxic Effects of Oxalic Acid by the Alkaline Comet Assay and QRT PCR in Human Buccal Epithelial Cells. AB - OBJECTIVE: To evaluate the cytogenetic and genotoxic effects of oxalic acid. STUDY DESIGN: Buccal epithelial cells were obtained and cells were suspended in phosphate buffered saline. Increasing amounts of oxalic acids were added to cell suspensions and incubated in 37 degrees C, 5% CO2 for 30 minutes. Comets were scored using a computer-based image analysis system, and tail moments were taken as a measure of DNA damage. The transcriptional changes of HIPK2, GADD45A, DDB2, p53, PCNA, NBS1, and MDM2 genes were also investigated by qRT-PCR using B2M and GAPDH genes as references. RESULTS: It was found that DNA damage occurred in parallel with increasing amounts of oxalic acid according to tail moment measurements, and also expressions of the selected genes have increased. CONCLUSION: It can be concluded that along with increasing amounts of oxalic acid, cell damage was detected, and both comet assay and expression of the selected genes can be used in the assessment of the damage caused by oxalic acid. PMID- 26860012 TI - Extravesical Pagetoid Spread of Urothelial Carcinoma in Situ. A Report of Five Cases. AB - BACKGROUND: Urothelial carcinoma in situ (CIS) of the bladder is classified as a flat lesion of the urothelium; it has a tendency to be multifocal and carries a high risk of recurrence and persistence. Approximately one-third of patients with urothelial CIS of the bladder develop invasive carcinoma if left untreated. There are a few reported cases of extravesical intramucosal extension (pagetoid spread) of urothelial CIS without prior documentation of primary muscle-invasive carcinoma. CASES: We present 5 cases of urothelial CIS that exhibited pagetoid spread to prostatic ducts, seminal vesicles, and the vagina. CONCLUSION: Pagetoid spread of urothelial CIS of the bladder may introduce uncertainty with regard to assignment of proper disease staging, and therefore uncertainty about appropriate cancer management. PMID- 26860011 TI - Clinicopathological Significance of Matrix Metalloproteinase-2 Protein Expression in Renal Cell Carcinoma Patients. AB - OBJECTIVE: To conduct a metaanalysis in order to determine the association between matrix metalloproteinase (MMP)-2 expression and renal cell carcinoma (RCC) progression. STUDY DESIGN: Cohort studies were identified after an exhaustive search of the following electronic databases: PubMed, China Biomedicine, Web of Science, Wanfang database, and China National Knowledge Infrastructure. Summary odds ratios with 95% confidence interval were calculated. RESULTS: Seventeen clinical studies were eligible for the present metaanalysis. Overall, increased MMP-2 protein expression levels had a positive correlation with several RCC clinical parameters, such as tumor node metastasis (TNM) stage, differentiation grade, lymph node metastasis (LNM), and tumor size (all p < 0.05). Country-stratified analysis revealed statistically significant differences in MMP-2 expression levels, based on the 4 clinical parameters studied, in the Chinese population (all p < 0.05). The results indicated that the MMP-2 protein level in RCC patients with non-clear cell type was higher than that in the patients with clear cell carcinoma (p < 0.05). A positive correlation was found between RCC differentiation grade and MMP-2 protein levels in only the streptavidin-peroxidase subgroup (p < 0.05), while there were significant associations between MMP-2 protein level and TNM stage, LNM, and tumor size (p < 0.05). CONCLUSION: Our metaanalysis suggests that RCC patients with a high MMP-2 expression level exhibit rapid progression of RCC and that high MMP-2 expression level is associated with poor prognosis. PMID- 26860013 TI - Renal Leiomyosarcoma. A Report of Two Cases. AB - BACKGROUND: Leiomyosarcoma represents a rather uncommon malignancy, and reports of cases characterized by a renal genesis are particularly rare. CASES: We describe 2 cases of leiomyosarcoma of the kidney, in a 63-year-old woman and in a 53-year-old man, respectively. Both tumors share a common immunohistochemical profile with a strong positivity for smooth muscle actin, a focal positivity for desmin, and negativity for cytokeratins and other markers. CONCLUSION: We provide a comparison between our findings and the data available in the literature, and we note an interesting relatively long survival in our patients (10 months for the first case and 20 months for the second case). PMID- 26860014 TI - UNUSUAL RESPONSE TO MUSCLE RELAXANTS IN THE PREGNANT WOMAN UNDERGOING CESAREAN SECTION. PMID- 26860015 TI - COMPARISON OF THE EFFECTS OF INTRAPLEURAL BUPIVACAINE AND MORPHINE ON POST THORACOTOMY PAIN. AB - BACKGROUND: Post-thoracotomy pain is the most severe types of postoperative pain. This study compares the effects of intrapleural bupivacaine and morphine on post thoracotomy pain. METHODS: In a double blind clinical trial study, 30 patients candidate for unilateral thoracotomy were randomly divided into bupivacaine and morphine groups. Patients in the morphine group received 0.2 mg/kg morphine and those in the bupivacaine group received 1 mg/kg bupivacaine by an intrapleural catheter placed at the end of surgery by direct vision. Intrarpleural morphine and bupivacaine continued every 4 hours for the next 24 hours. If required, systemic analgesia with morphine (patient-controlled analgesia, PCA) also used as a postoperative analgesic. The amount of morphine consumption and level of postoperative pain at 2, 6, 12 and 24 hours after surgery were recorded. RESULTS: Patients did not differ significantly in terms of age, gender and duration of surgery. There were no significant differences between the two groups with regard to their mean score of pain at 2 and 6 hours of the surgery; however, the level of pain was significantly lower in the bupivacaine group compared to the morphine group at 12 and 24 hours of the surgery. In the bupivacaine group, the mean level of intravenous opioid used over the 24 hours following surgery was significantly lower than in the morphine group. DISCUSSION: Intrapleural injection of bupivacaine can be more effective in reducing post-thoracotomy pain compared to intrapleural morphine. PMID- 26860016 TI - RAPID FLUID ADMINISTRATION AND THE INCIDENCE OF HYPOTENSION INDUCED BY SPINAL ANESTHESIA AND EPHEDRINE REQUIREMENT: THE EFFECT OF CRYSTALLOID VERSUS COLLOID COLOADING. AB - PURPOSE: Spinal anesthesia for caesarean delivery is often associated with hypotension. This study was conducted to evaluate the effects of rapid crystalloid (Lactated Ringer's solution; LRS) or colloid (hydroxyethyl starch; HES) cohydration with a second intravenous access line on the incidence of hypotension and ephedrine requirement during spinal anesthesia for cesarean section. METHODS: We studied 90 women with uncomplicated pregnancies undergoing elective cesarean section under spinal anesthesia. Intravenous access was established in all patients with two peripheral intravenous lines, the first being used for the baseline volume infusion. Immediately after induction of spinal anesthesia, LRS (Group L) or HES (Group C) infusions were started at the maximal possible rate via the second line in groups L and C respectively. In the third group (Group E), patients received lactated Ringer's solution at a 'keep vein open' rate to maintain the double-blind nature. The incidence of hypotension, ephedrine requirements, total amount of volume and side effects were recorded. RESULTS: The incidence of hypotension was significantly greater in group E than in groups L and C, and greater in group L than in group C (p < 0.03 and p < 0.01 respectively ). The total dose of ephedrine used to treat hypotension was significantly less in groups L and C than in group E (p < 0.001 and p < 0.001 respectively). Groups L and C received similar infusion volumes and doses of ephedrine. CONCLUSIONS: Giving either LR or HES coloading via a second IV line caused less hypotension and required less use of ephedrine compared to no coloading. There were no maternal or neonatal side effects. PMID- 26860017 TI - OPIOID ADMINISTRATION AS PREDICTOR OF PEDIATRIC EPIDURAL FAILURE. AB - BACKGROUND: Increasing use of regional analgesia in pediatric populations requires a better understanding of when analgesic techniques need revising or supplementation. This study was conducted to examine intra-operative opioid use as a predictor of post-operative epidural failure. METHODS: Retrospective chart review of patients having epidurals placed intra-operatively. 229 epidurals were placed during the study, with 75 excluded. Dosing and quantity of opioids used intra-operatively were compared to the primary outcome of epidural failure, as well as duration of infusions and pain scores. RESULTS: Opioid use was associated with increased epidural failure, particularly in less than 12 hours. However, no distinct point of certain epidural failure was found. CONCLUSIONS: Opioid use after epidural loading correlates with increasing risk for epidural failure. Anesthesia providers should consider replacing or supplementing epidurals with increasing use of opioids. PMID- 26860018 TI - COMPARISON OF PRE-EMPTIVE EFFECT OF MELOXICAM AND CELECOXCIB ON POST-OPERATIVE ANALGESIA: A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL. AB - INTRODUCTION: Pre-emptive analgesia may reduce pain, accelerate recovery and shorten the duration of hospitalization. The present study aims to compare the preemptive analgesic effects of meloxicam and celecoxib in patients undergoing lower limb surgery. METHOD: In this double blind randomized clinical trial, 70 patients, undergoing lower extremity surgery, entered in the study; thirty five patients were randomly allocated to either group using random allocation software. Meloxicam (15 mg) was administered orally to one group two hours before the surgical onset. The other group was treated with oral celecoxib (400 mg) two hours before the operation. Pain severity was compared between the two groups. RESULTS: Upon admission to Recovery Room, the mean pain severity was not significantly different between the two groups. At one and two hours following surgery the mean pain severity was significantly higher in celecoxib group. However, 6 hours following surgery mean pain severity was higher with meloxicam administration. Pain severity was not significantly different in the two groups, 12 and 24 hours following surgery. CONCLUSION: The analgesic effect of celecoxib seems to cover longer duration than meloxicam; but, meloxicam appears to be a stronger analgesic in shorter time interval. PMID- 26860019 TI - CLINICAL RESEARCH REGARDING PREEMPTIVE ANALGESIC EFFECT OF PREOPERATIVE KETAMINE AFTER TRANSURETHRAL RESECTION OF PROSTATE. AB - OBJECTIVE: To investigate whether a single intravenous dose of ketamine before transurethral resection of prostate (TURP) led to reduced postoperative pain and tramadol consumption. METHODOLOGY: Sixty patients undergoing elective TURP were randomized into one of two groups: the ketamine group (Group K, n = 30) received intravenous 0.5 mg/kg ketamine 10 min before surgery, and the control group (Group C, n = 30) received an equivalent volume of normal saline 30 min before surgery. A standardized general anesthesia method was used with a laryngeal mask airway device in all patients. Data on pain intensity, incidence of lower urinary tract discomfort, time to the first analgesic requirement, tramadol analgesia and consumption, overall patient satisfaction and side effects were recorded for 24 h after extubation of the patients. RESULTS: Group K had significantly decreased postoperative pain scores at 1, 2, 6, and 12 h. The number of patients who required postoperative analgesia was fewer and postoperative tramadol consumption was significantly less in Group K as compared with Group C. There was no significant difference in the incidence of lower urinary tract discomfort or any of side effects. The patients in Group K were more satisfied. CONCLUSION: Preemptive 0.5 mg/kg ketamine has a definitive role of preemptive analgesia for TURP without influence of LUT discomfort or an increase of adverse effects. PMID- 26860020 TI - "ANESTHETIC SPARING EFFECT OF INTRAOPERATIVE LIGNOCAINE OR DEXMEDETOMIDINE INFUSION ON SEVOFLURANE DURING GENERAL ANESTHESIA". AB - BACKGROUND: Lidocaine and Dexmedetomidine are known to blunt the stress response to surgery, and have anesthetic sparing activity. This study was designed to evaluate and compare the anesthetic sparing effect of intravenous lidocaine with Dexmedetomidine infusion during sevoflurane based general anesthesia and also to assess their effects on hemodynamic parameters. METHODS: Forty-eight ASA I-II patients aged between 18-55 yr, scheduled for abdominal surgery lasting less than 2 h, performed under general anesthesia were enrolled and they were randomly allocated to Lidocaine(L), Dexmedetomidine (D) and Saline (S) groups of 16 each. Group L received Inj. Lidocaine at 1.5 mg/kg bolus over 10 min followed by infusion at 1.5 mg/ kg/hr, and Group D received Inj. Dexmedetomidine at 1 MUg/kg over 10 min, followed by 0.5 MUg/ kg/hr infusion till the end of surgery. Group S received similar volume of normal saline. Anesthesia was induced with Inj. Propofol and maintained with N2O in O2 and sevoflurane, keeping entropy between 40-60. The hourly sevoflurane requirements and hemodynamic parameters were recorded. Results: Demographic parameters, entropy and duration of surgery were comparable. Mean sevoflurane requirement at 1st h in group L and D were 11.6 +/- 1.5 ml, and 10.2 +/- 1.3 ml respectively, while it was 16.7 +/- 4.1 ml in Saline group (P < 0.001). Sevoflurane requirements were significantly lesser in group D compared to group L (P = 0.009). The Mean ET(sevo) concentrations in Group L, D and S were 0.8 +/- 0.3, 0.8 +/- 0.4 and 1.2 +/- 0.5 (P = 0.021), respectively. CONCLUSIONS: Both drugs produce significant anesthetic sparing effect during sevoflurane based general anesthesia, but dexmedetomidine has better sparing effect than lignocaine. PMID- 26860021 TI - SUBMUCOSAL DISSECTION OF THE RETROPHARYNGEAL SPACE DURING NASAL INTUBATION. AB - Various complications have been reported with nasal endotracheal intubation including bleeding, epistaxis, bacteremia, damage to intranasal structures, and even intracranial penetration. We present two cases that required general anesthesia for dental surgery. Submucosal dissection of the retropharyngeal tissues occurred during attempted nasal endotracheal intubation. Previous reports of this complication are reviewed, treatment strategies presented, and potential maneuvers to prevent this complication suggested. PMID- 26860022 TI - A PROSPECTIVE RANDOMIZED COMPARATIVE STUDY TO COMPARE THE HEMODYNAMIC AND METABOLIC STRESS RESPONE DUE TO ENDOTRACHEAL INTUBATION AND I-GEL USAGE DURING LAPAROSCOPIC CHOLECYSTECTOMY. AB - BACKGROUND: Surgery and endotracheal intubation both causes an increase in metabolic stress response. This is further aggravated during laparoscopic surgeries. In this study we aimed at comparing hemodynamic and metabolic parameters which are reflective of intraoperative stress response while using I GEL against endotracheal tube (ETT) during laparoscopic cholecystectomy. MATERIAL AND METHODS: This is a prospective randomized comparative study among 64 cases of American Society of Anesthesiologists(ASA) physical status class I and II, undergoing laparoscopic cholecystectomy who were randomly allocated into two groups of 32 each using computer generated random number table. Patients were put under general anesthesia using standard protocol. After anesthesia induction and 20 minutes after induction venous blood samples were obtained for measuring adrenalin, noradrenalin, dopamine and cortisol levels. Hemodynamic and respiratory parameters were recorded at the 1st, 5th, 15th, 30th and 45th minutes after the insertion of airway device. RESULTS: Although there was no significant difference regarding ventilatory parameters there was significant increase in heart rate at 1st and 45th minutes (p = 0.02 and 0.034) respectively and increase in mean arterial pressure at 15th and 30th minutes(p = 0.034 and 0.026) respectively in the ETT group compared to I-GEL group. Stress hormone intergroup analysis revealed significant increase in serum cortisol 20 minutes after induction in ETT group as compared to I-GEL group (p = 0.03). CONCLUSION: I-GEL usage is a suitable, effective and safe alternative to ETT in laparoscopic cholecystectomy patients with lower metabolic stress response. PMID- 26860023 TI - COMPARATIVE EVALUATION OF PLAIN AND HYPERBARIC ROPIVACAINE IN PATIENTS UNDERGOING LOWER ABDOMINAL SURGERY UNDER SPINAL ANESTHESIA. AB - BACKGROUND: Preliminary work has shown that ropivacaine provides spinal anesthesia of shorter duration with greater sensory motor dissociation than bupivacaine, and may be of particular use in the day care surgery. Hypothetically, hyperbaric solution of ropivacaine could improve and shorten both sensory and motor block. MATERIAL AND METHODS: This prospective, randomized, double blind study was conducted on 80 patients undergoing lower abdominal surgeries. Patients either received 20.25 mg of plain ropivacaine (group A) or 20.25 mg of hyperbaric ropivacaine in 5% dextrose (group B). The extent and duration of sensory and motor block, haemodynamics, time to home readiness, and the time to first rescue analgesia were recorded. RESULTS: All patients in group B achieved sensory block at or above T10 dermatome in comparison to only 87.5% patients of group A. Analgesia at T10 was reached in 4 min (4-6 min) in group B vs. 10 min (6-16 min) in group A (p < 0.001). Patients in group B had a longer duration of analgesia at T10; 126 min (97-146 min) vs. 110 min (90-128 min) (p = 0.047). Median duration of sensory block from injection of the anesthetic to complete recovery (regression to S2 dermatome) was shorter in Group B than Group A, 273.5 min (258 - 289 min) vs. 300 min (290 - 312 min) (p < 0.001), as was the time to 2 segment regression 80 min (63-90 min) vs. 102 min (82-124 min) (p < 0.001). Duration of complete motor block (mean +/- SD) was significantly less in group B, 93.06 +/- 17.38 min compared to 139.89 +/- 25.17 min (p < 0.001) in group A, as was the total duration of motor block (181.83 +/- 30.21 min in group B vs. 254.91 +/- 25.34 min in Group A; p < 0.001). Patients in Group B attained discharge criteria earlier as indicated by a shorter time to home readiness. Cardiovascular changes were unremarkable throughout, and similar in the two groups. There were no major sequelae. CONCLUSION: Addition of dextrose 5% to ropivacaine increases the speed of onset, block reliability, duration of useful block for surgery and speed of recovery. Plain solutions are less reliable for surgery above a dermatomal level of T10. PMID- 26860024 TI - THE BENEFICIAL VALUES OF TRANSOESOPHAGEAL DOPPLER IN INTRAOPERATIVE FLUID GUIDANCE VERSUS STANDARD CLINICAL MONITORING PARAMETERS IN INFANTS UNDERGOING KASAI OPERATION. AB - BACKGROUND: Fluid overload in infants can result from inappropriate volume expansion (VE). The aim of this work was to evaluate the beneficial values of Transoesophageal Doppler TED in intraoperative fluid guidance versus standard clinical monitoring parameters in infants undergoing Kasai operation. METHODS: Forty infants scheduled for Kasai procedure were randomly allocated into two groups (Doppler and clinical group). In Doppler group decided to provide VE (10 30 mI/kg of Eydroxyethyl starches HES) when the index stroke volume decreased by >= 15% from the baseline value, in clinical group, hemodynamic variables triggering colloid administration mean arterial blood pressure (MAP) less than 20% below baseline or central venous pressure (CVP) < 5 cmH2O in both groups: Ringer's acetate was infused at constant rate (6 m l/kg/h). Standard and TED derived data were recorded before and after VE. Follow up the postoperative outcome and hospital stay. RESULTS: There were significantly lower mean volume of HES (42.85 +/- 3.93 versus 84 14.29 ml) and percent of infants required it (30% versus 90%) associated with earlier tolerance to oral feeding (2 +/- 0.66 versus 3.4 +/- 0.51), shorter hospital stay (5.30 +/- 0.47 versus 6.7 +/- 0.92 days) and lower rate of chest infection (15% versus 30%) in Doppler group than clinical group. There was no difference between the two studied groups regarding heart rate, MAP. CONCLUSIONS: TED guided intraoperative fluid intake in infants undergoing Kasai operation optimize fluid consumption and improve outcome associated with shorter hospital stay. PMID- 26860025 TI - BILATERAL ADDUCTOR VOCAL CORD PALSY: COMPLICATION OF PROLONGED INTRAOPERATIVE HYPOTENSION AFTER ENDOTRACHEAL INTUBATION. AB - Endotracheal intubation for general anesthesia is usually a safe procedure. However, postoperative sore throat and mild hoarseness may occur due to laryngeal edema but bilateral vocal cord paralysis as a result of recurrent laryngeal nerve injury is a rare complication. We report a case of bilateral adductor vocal cord palsy following general anesthesia for abdominal surgery. Clinical presentation was hoarseness, aspiration pneumonia and hypoxemia requiring ventilatory support. Neuropraxia of recurrent laryngeal nerve due to prolong intra-operative hypotension, even with normal endotracheal tube cuff pressure was the likely mechanism. PMID- 26860026 TI - ANESTHESIA MANAGEMENT IN AN INFANT WITH GLYCOGEN STORAGE DISEASE TYPE II (POMPE DISEASE). AB - Pompe or Glycogen Storage Disease type II (GSD-II) is a genetic disorder affecting both cardiac and skeletal muscle. Historically, patients with the infantile form usually die within the first year of life due to cardiac and respiratory failure. Recently a promising enzyme replacement therapy has resulted in improved clinical outcomes and a resurgence of elective anesthesia for these patients. Understanding the unique cardiac physiology in patients with GSD-II is essential to providing safe general anesthesia. Additional care in maximizing coronary perfusion pressure and minimizing arrhythmia risk must be given. For these reasons, it is recommended that anesthesia for infantile Pompe patients should specifically avoid propofol or high concentrations of sevoflurane and, instead, use an agent such as ketamine as the cornerstone for induction in order to better support coronary perfusion pressure and to avoid decreasing diastolic blood pressure (DBP) with vasodilatory agents. We present the anesthetic technique in a case of infantile type Pompe disease. PMID- 26860027 TI - RECURARIZATION AFTER ACUTE INTRAOPERATIVE NORMOVOLEMIC HEMODILUTION AND USE OF SUGAMMADEX. AB - Acute normovolemic hemodilution (ANH) is a blood conservation procedure that can be used in cases of refusal of blood transfusion for religious reasons. Herein, we describe a case of recurarization after reinfusion of collected blood. A combination of rocuronium/sugammadex has the potential to increase the safety of patients if ANH is done after induction. Prospective controlled studies evaluating this unique indication for sugammadex use are thus warranted. PMID- 26860028 TI - MALPOSITIONED LMA CONFUSED AS FOREIGN BODY IN NASAL CAVITY. AB - We present a case of confusing white foreign body in the nasal cavity detected during Endoscopic Sinus Surgery (ESS) in a 35-yr-old male which turned out to be a malposition of classic laryngeal mask airway (LMA). Although malposition of LMA is a known entity to the anesthesiologist, if ventilation is adequate, back folded LMA in nasal cavity might not be recognized by the surgeon and lead to catastrophic consequences during endoscopic sinus surgery. In principle, misfolding and malpositioning can be reduced by pre usage testing, using appropriate sizes, minimizing cuff volume, and early identification and correction of malposition. PMID- 26860029 TI - AIRTRAQ8 OPTICAL LARYNGOSCOPE FOR TRACHEAL INTUBATION IN A PATIENT WITH AN UNCOMMON GIANT LIPOMA ON THE POSTERIOR ASPECT OF NECK AND ADDITIONAL RISK FACTORS OF ANTICIPATED DIFFICULT AIRWAY: A CASE REPORT. AB - Patients with restricted neck movement present a difficult airway situation because of improper positioning and inadequate extension of the atlanto-occipital joint. The Airtraq optical laryngoscope is a new single use device that permits an indirect view of the glottis without the need to achieve a direct line of sight by conventional use of the 'sniffing position'. We present and discuss a case of uncommon giant lipoma (16 x 12 x 10 cm) in the posterior aspect of the neck in addition with other independent factors of anticipated difficult airway, intubated successfully in the semi-lateral position with the use of Airtraq. PMID- 26860030 TI - DIAGNOSIS OF AORTIC THROMBUS AFTER PELVIC SURGERY. PMID- 26860031 TI - BILATERAL SUPERFICIAL CERVICAL BLOCKS AS THE PRIMARY ANESTHETIC FOR THE PATIENT UNDERGOING AN EVACUATION OF NECK HEMATOMA AFTER PARATHYROID SURGERY. AB - This is the case of an 80-year-old female who presented for evacuation of a neck hematoma on POD#3 after a parathyroidectomy. Her medical history included coronary artery disease with a drug-eluding stent, off aspirin for 2 weeks. She had a significant hematoma from the hyoid bone extending down to below the suprasternal notch. She reported hoarseness. The anesthesiology team provided regional anesthesia with bilateral superficial cervical blocks, supplemented with minimal sedation for patient compliance. The surgical team used no adjuvant local anesthetic. A deep exploration was performed and significant clot was evacuated. The patient went home safely from the PACU. PMID- 26860032 TI - EXTRA CORPOREAL MEMBRANE OXYGENATION IN ACUTE RESPIRATORY DISTRESS SYNDROME. AB - A young female presented with pneumonitis and worsened acute respiratory distress syndrome (ARDS) failed all the conservative ventilator management, was managed with extra corporeal life support technology, and was successfully discharged. PMID- 26860033 TI - SEVEN-DAY HOSPITAL MODEL: A FUTURISTIC ACTUALITY. PMID- 26860034 TI - DOES CISATRACURIUM AT A CLINICAL DOSE ATTENUATE THE IMMUNOSUPPRESSION AFTER SURGERY IN SMOKING PATIENTS WITH NON-SMALL CELL LUNG CANCER? PMID- 26860035 TI - POSS-Based Electrolyte for Efficient Solid-State Dye-Sensitized Solar Cells at Sub-Zero Temperatures. AB - To expand the application of solid-state dye-sensitized solar cells (ssDSSCs) to low temperatures, it is necessary to develop new solid electrolytes with low glass transition temperature (Tg). The Tg is regulated by varying the length of alkyl chain that is connected with the nitrogen atom in the imidazolium ring linked to the polyhedral oligomeric silsesquioxane (POSS). The Tg as low as -8.8 degrees C is achieved with the POSS grafted with methyl-substituted imidazolium. The effect of alkyl group on the conductivity, Tg, and photovoltaic performance has also been investigated. The conductivity and power conversion efficiency increase with the alkyl length, while the Tg first increases and then decreases with the alkyl length. Among the synthesized POSS-based ionic conductors, the POSS grafted with the methyl-substituted imidazolium yields the highest power conversion efficiency of 6.98% at RT due to its highest conductivity, and the efficiency (6.52%) is still good at -4 degrees C, as its Tg (-8.8 degrees C) is lower than the working temperature (-4 degrees C). This finding suggests that the POSS-based solid electrolyte is promising for subzero-temperature applications of ssDSSCs. PMID- 26860036 TI - Using the galectin-3 test to predict mortality in heart failure patients: a systematic review and meta-analysis. AB - AIM: Galectin-3 (Gal-3) is a new biomarker for assessing prognosis of heart failure (HF) patients. This systemic review and meta-analysis aims to examine Gal 3's ability in assessing prognosis of HF patients. METHOD: We searched MEDLINE and Embase up to November 2014. Test performance characteristics were summarized using forest plots and hierarchical summary receiver operating characteristic curves. RESULTS: The diagnostic odds ratio of Gal-3 in predicting mortality in chronic HF patients was 2.36 (95% CI: 1.71-3.26) and 2.30 (95% CI: 1.76-3.01) in acute HF patients. CONCLUSION: Elevated levels of Gal-3 are associated with mortality in both acute and chronic HF patients. However, current evidence does not support sole use of Gal-3 for prognosis evaluation of HF patients. PMID- 26860037 TI - Communication About Problematic Drinking Between Young Adults and their Parents: An Application of Inconsistent Nurturing as Control Theory. AB - Approximately 80% of college students drink, half of whom consume alcohol in the form of binge drinking. The current study applies Inconsistent Nurturing as Control Theory to examine the communication about excessive drinking that takes place between parents and their young adult children. Forty college students were asked to report on a moment or incident that led their parents to label their drinking as concerning and were then asked to report on how their parents acted towards the drinking before and after the moment of labeling. Interviews were transcribed and coded. The findings suggest that parents act with inconsistency when attempting to manage their children's drinking by enacting both reinforcing and punishing behaviors. Parents' reinforcing behaviors included drinking with their children and buying them alcohol, even after labeling the drinking as problematic. Parents' punishment behaviors included expressing concern about their children's sense of responsibility and making their children feel regretful about their drinking. Nearly 88% of the participants were able to recall the moment at which their parents labeled their drinking as problematic. Implications for using inconsistent messages in conversations about alcohol are discussed. PMID- 26860038 TI - A mesoporous biomaterial for biomimetic crystallization in dentinal tubules without impairing the bonding of a self-etch resin to dentin. AB - BACKGROUND/PURPOSE: CaCO3@mesoporous silica reacted with phosphoric acid (denoted as CCMS-HP) enables the growth of calcium phosphate crystals in dentinal tubules. This study tested whether CCMS-HP could be used to form a biomimetic barrier on the exposed dentin for prevention of dentin sensitivity without impairing the bonding of Single Bond Universal (SBU) self-etch adhesive to the dentin. METHODS: Twenty-four dentin disks were prepared and divided into three groups: (1) SBU group (n = 8), in which SBU self-etch adhesive was bonded to the dentin disk directly; (2) CCMS-HP group (n = 8), in which CCMS-HP was applied onto the dentin surface; and (3) CCMS-HP/SBU group (n = 8), in which the dentin surface was first treated with CCMS-HP and then boned by SBU. The permeation depth of crystals into the dentinal tubules was examined and measured with a scanning electron microscope. The shear bonding strength of SBU and CCMS-HP/SBU to dentin was also measured. RESULTS: The mean crystal permeation depth was 35.8 +/- 6.9 MUm for the CCMS-HP/SBU group and 33.6 +/- 12.2 MUm for the CCMS-HP group; no significant difference was found between the two groups. Moreover, the mean shear bonding strength was 22.7 +/- 6.7 MPa for the CCMS-HP/SBU group and 23.3 +/- 7.0 MPa for the SBU group. There was also no significant difference between the two groups. CONCLUSION: CCMS-HP can be used to form a biomimetic barrier for prevention of dentin sensitivity because it neither impedes the bonding of SBU to dentin nor impairs the shear bonding strength between the SBU and dentin. PMID- 26860039 TI - Performance analysis of seismocardiography for heart sound signal recording in noisy scenarios. AB - This paper presents a system based on Seismocardiography (SCG) to monitor the heart sound signal for the long-term. It uses an accelerometer, which is of small size and low weight and, thus, convenient to wear. Such a system should also be robust to various noises which occur in real life scenarios. Therefore, a detailed analysis is provided of the proposed system and its performance is compared to the performance of the Phoncardiography (PCG) system. For this purpose, both signals of five subjects were simultaneously recorded in clinical and different real life noisy scenarios. For the quantitative analysis, the detection rate of fundamental heart sound components, S1 and S2, is obtained. Furthermore, a quality index based on the energy of fundamental components is also proposed and obtained for the same. Results show that both the techniques are able to acquire the S1 and S2, in clinical set-up. However, in real life scenarios, we observed many favourable features in the proposed system as compared to PCG, for its use for long-term monitoring. PMID- 26860041 TI - Tissue Expansion Technique for Desyndactylization of Toes Using an External Fixator. AB - We present an alternative technique for desyndactylization of toes using soft tissue traction with an external fixator. This method allows for tissue expansion for subsequent skin plasty, thereby avoiding the need for a graft or complicated local skin rearrangement. The use of the conventional acute correction technique can create more scarring and might increase the potential for complications, especially if the graft is obtained from a remote site. We believe that this technique provides a satisfactory functional and cosmetic outcome. This method has the potential to minimize postoperative complications, provide functional digits, and allow for good cosmetic results. PMID- 26860040 TI - Inverted optical intrinsic response accompanied by decreased cerebral blood flow are related to both neuronal inhibition and excitation. AB - Negative hemodynamic response has been widely reported in blood oxygenation level dependent (BOLD) functional magnetic resonance imaging studies, however its origin is still controversial. Optical intrinsic signal (OIS) imaging can be used to study brain activity by simultaneously recording hemodynamic signals at different wavelengths with high spatial resolution. In this study, we found transcorneal electrical stimulation (TcES) could elicit both positive OIS response (POR) and negative OIS response (NOR) in cats' visual cortex. We then investigated the property of this negative response to TcES and its relationship with cerebral blood flow (CBF) and neuronal activity. Results from laser speckle contrast imaging showed decreased CBF in the NOR region while increased CBF in the POR region. Both planar and laminar electrophysiological recordings in the middle (500-700 MUm) cortical layers demonstrated that decreased and increased neuronal activities were coexisted in the NOR region. Furthermore, decreased neuronal activity was also detected in the deep cortical layers in the NOR region. This work provides evidence that the negative OIS together with the decreased CBF should be explained by mechanisms of both neuronal inhibition and excitation within middle cortical layers. Our results would be important for interpreting neurophysiological mechanisms underlying the negative BOLD signals. PMID- 26860042 TI - Atypical Presentation of Fibrolipomatous Hamartoma of Superficial Peroneal Nerve. AB - Fibrolipomatous hamartoma is a rare presentation in the foot. An accurate diagnosis is key, with magnetic resonance imaging findings considered definitive. The management is dependent on the symptoms. We present an atypical presentation of fibrolipomatous hamartoma of the superficial peroneal nerve and discuss the current published data. PMID- 26860043 TI - Classification and Outcome of Fracture-Dislocation of the Cuneiform Bones. AB - Fractures and dislocations of the cuneiform bones are rare injuries to the midtarsal foot. The injury severity is often unclear, and the prognostic factors are unknown. The purpose of the present study was to characterize our insights of the diagnostics, therapy, and fracture patterns. We questioned whether the number of involved cuneiform bones and the type of injury would affect the clinical outcome. With this information, we aimed to develop a classification system for injuries of the cuneonavicular joint. Five patients who had sustained complex fracture-dislocation of the cuneiform bones were prospectively registered, underwent surgery, and were followed. We reviewed the published data and found 47 reports that included 55 patients to improve the informative value of our study. The injury mechanisms and therapy were evaluated, and the postoperative limitations and pain were assessed. The clinical outcome was correlated with the number of involved cuneiforms and the fracture/dislocation pattern. Direct trauma was associated with isolated fracture, and indirect injury was associated with isolated dislocations. Occasionally, these injuries were overlooked on conventional radiographs, and closed reduction frequently failed. The number of cuneiform bones involved and the type of injury were shown to affect the clinical outcome. We devised an easily applicable classification system for injuries to the cuneiform bones using this information. All cases were classified as isolated fractures (1), isolated dislocations (2), or fracture-dislocations (3) involving 1 (A), 2 (B), or 3 (C) cuneiform bones. The classification system we propose will facilitate a better understanding of the fracture patterns at the cuneonavicular joint line and is a good prognostic tool that requires validation in clinical settings. PMID- 26860044 TI - Subtalar Fusion and Arthroereisis. PMID- 26860045 TI - Insertional Characteristics of the Peroneus Tertius Tendon: Revisiting the Anatomy of an Underestimated Muscle. AB - The present study was performed to describe the morphologic characteristics of the peroneus tertius (PT) tendon, evaluate the variations in its insertion point, investigate the interconnections with the tendons of the extensor digitorum longus, and discuss whether these insertion differences of the muscle tension might have an effect on fracture formation. The length and width of the PT tendon and the width at its midpoint were measured in 44 lower extremities. The data obtained were compared statistically. The PT was found to occur in 2 types according to the number of tendons: type 1, a single tendon without a slip; and type 2, 2 tendons with a slip. It has been suggested that the PT tendon could contribute to avulsion fractures of the tuberosity of the fifth metatarsal bone. Therefore, to understand the mechanism of Jones fracture, knowledge of the PT tendon would be beneficial to determine the insertion points. PMID- 26860046 TI - Failure of Internal Fixation for Painful Bipartite Navicular in Two Adolescent Soccer Players: A Report of Two Cases. AB - Bipartite navicular bone is an uncommon condition that can cause midfoot pain in children and adolescents. No treatment methods, other than conservative management, have been reported. We report the cases of 2 adolescent soccer players who underwent internal fixation of the painful bipartite fragments, resulting in nonunion. After failure of conservative management, the patients underwent surgery. Curettage of the junction between the 2 bone fragments was performed, and autologous cancellous bone was grafted. Next, the fragments were fixed with variable-threaded screws. Bone union of the bipartite fragments was once achieved on computed tomography in both cases at 3 and 5 months after surgery, respectively. However, separation of the fragment occurred in both cases after the patients had returned to sports. Although the patients were able to return to sports activities, they still had mild midfoot pain 3 and 2 years after surgery, respectively. Internal fixation using screws and an autologous bone graft for painful bipartite navicular bone in adolescent athletes is not recommended, and other surgeries should be considered to achieve bony union. PMID- 26860047 TI - Arthroscopic Resection of Symptomatic Ossicle of the Medial Malleolus: A Case Report. AB - An ossicle around the medial malleolus is difficult to differentiate from an unfused ossification center, an avulsion fracture, and os subtibiale. Misdiagnosis can lead to inappropriate or unnecessary treatments. We describe a patient with a symptomatic ossicle of the medial malleolus in the left ankle that prevented participation in sports activities because of medial ankle pain. Plain radiography and computed tomography revealed a small ossicle associated with the anterior colliculus of the medial malleolus. Conservative treatment failed, and the patient underwent ankle arthroscopy. Instability of the ossicle was identified after the hypertrophic inflammatory synovium had been debrided. The ossicle was resected in a step-by-step manner with an arthroscopic shaver and grasper through the anteromedial accessary portal. The deltoid ligament sustained minimal damage after resection. The patient fully recovered and was able to return to sports activities 3 months after surgery. Arthroscopic resection of the ossicle at the medial malleolus requires no additional treatments of the deltoid ligament, effectively relieves symptoms, and enables the patient to return to full preinjury activities. PMID- 26860049 TI - A study of thin film solid phase microextraction methods for analysis of fluorinated benzoic acids in seawater. AB - Fluorinated benzoic acids (FBAs) are frequently used as tracers by the oil industry to characterize petroleum reservoirs. The demand for fast, reliable, robust, and sensitive approaches to separate and quantify FBAs in produced water, both in laboratory and field conditions, has not been yet fully satisfied. In this study, for the first time, thin film solid phase microextraction (TF-SPME) is proposed as a versatile sample preparation tool for the determination of FBAs in produced water by pursing two different approaches. First, an automated high throughput TF-SPME method using solvent desorption for fast and simultaneous preparation of multiple samples prior to liquid chromatographic separation and high resolution mass spectrometric detection (LC-MS) of FBAs was demonstrated for routine laboratory analysis. This method was optimized in terms of extraction phase chemistry, sample pH and ionic strength, extraction/desorption times using two representative FBAs (4-FBA and 2,3,4,5-tetra FBA). It incorporates a relatively simple sample pretreatment involving pH adjustment prior to the TF SPME, and obtained limits of quantification (LOQ) are at the 1.0ngmL(-1) level. Second, the applicability of TF-SPME for fast mass spectrometric (MS) determination of FBAs with omission of derivatization and gas chromatographic (GC) separation was proven. This second method consists of manual extractions of analytes from seawater samples with a thermally stable TF-SPME membrane and direct thermal desorption of the extracted FBAs to a MS via a thermal desorption unit (TDU). It was demonstrated that the TF-SPME extracts and thermally releases analytes quantitatively and with good reproducibility. This approach opens up the possibility for on-site measurements with portable analyzers. PMID- 26860048 TI - Moderate chronic kidney disease impairs bone quality in C57Bl/6J mice. AB - Chronic kidney disease (CKD) increases bone fracture risk. While the causes of bone fragility in CKD are not clear, the disrupted mineral homeostasis inherent to CKD may cause material quality changes to bone tissue. In this study, 11-week old male C57Bl/6J mice underwent either 5/6th nephrectomy (5/6 Nx) or sham surgeries. Mice were fed a normal chow diet and euthanized 11weeks post-surgery. Moderate CKD with high bone turnover was established in the 5/6 Nx group as determined through serum chemistry and bone gene expression assays. We compared nanoindentation modulus and mineral volume fraction (assessed through quantitative backscattered scanning electron microscopy) at matched sites in arrays placed on the cortical bone of the tibia mid-diaphysis. Trabecular and cortical bone microarchitecture and whole bone strength were also evaluated. We found that moderate CKD minimally affected bone microarchitecture and did not influence whole bone strength. Meanwhile, bone material quality decreased with CKD; a pattern of altered tissue maturation was observed with 5/6 Nx whereby the newest 60MUm of bone tissue adjacent to the periosteal surface had lower indentation modulus and mineral volume fraction than more interior, older bone. The variance of modulus and mineral volume fraction was also altered following 5/6 Nx, implying that tissue-scale heterogeneity may be negatively affected by CKD. The observed lower bone material quality may play a role in the decreased fracture resistance that is clinically associated with human CKD. PMID- 26860050 TI - Surface-crosslinked poly(3-mercaptopropyl)methylsiloxane-coatings on silica as new platform for low-bleed mass spectrometry-compatible functionalized stationary phases synthesized via thiol-ene click reaction. AB - A thin functional film of poly(3-mercaptopropyl)methylsiloxane was coated onto vinyl-modified silica particles (5MUm, 100A pore size) and chemically crosslinked to the surface. Excess of thiol functionalities allow bonding of alkene containing ligands by thiol-ene click reaction in a second step (QN-VII). Besides that a single step surface modification procedure was established in which alkene functional ligands were directly added to the polysiloxane coating solution and thus, after evaporation of the solvent, crosslinking to the vinylized surface and bonding of chromatographic ligand to the thiolated polysiloxane film occur simultaneously in one step (QN-VI). Successful bonding of the polysiloxane film was confirmed for both approaches by (29)Si cross-polarization/magic angle spinning NMR spectra. The new surface functionalization concept can be utilized as a new platform for the preparation of various low-bleed, mass spectrometry compatible stationary phases with a variety of functional ligands. The concept was demonstrated by thiol-ene click reaction with quinine carbamate and its subsequent use for enantiomer separation by HPLC-UV and HPLC-ESI-QTOF-MS of acidic chiral analytes. Chromatographic enantioselectivities were similar to a comparable brush-type CSP (QN-V0). The greatly reduced background signal in LC MS, however, comes at expense of somewhat lower chromatographic efficiencies (C term by factor of 2 larger compared to brush-type CSP). For quantitative analysis in single reaction monitoring (MRM(HR)) in high sensitivity mode, limit of detection and limit of quantification results are comparable for both surface polymer modified CSPs, with only slightly higher values for the conventional brush-type CSP (QN-V0). PMID- 26860051 TI - Enhanced methodology for porting ion chromatography retention data. AB - Porting is a powerful methodology to recalibrate an existing database of ion chromatography (IC) retention times by reflecting the changes of column behavior resulting from either batch-to-batch variability in the production of the column or the manufacture of new versions of a column. This approach has been employed to update extensive databases of retention data of inorganic and organic anions forming part of the "Virtual Column" software marketed by Thermo Fisher Scientific, which is the only available commercial optimization tool for IC separation. The current porting process is accomplished by performing three isocratic separations with two representative analyte ions in order to derive a porting equation which expresses the relationship between old and new data. Although the accuracy of retention prediction is generally enhanced on new columns, errors were observed on some columns. In this work, the porting methodology was modified in order to address this issue, where the porting equation is now derived by using six representative analyte ions (chloride, bromide, iodide, perchlorate, sulfate, and thiosulfate). Additionally, the updated porting methodology has been applied on three Thermo Fisher Scientific columns (AS20, AS19, and AS11HC). The proposed approach showed that the new porting methodology can provide more accurate and robust retention prediction on a wide range of columns, where average errors in retention times for ten test anions under three eluent conditions were less than 1.5%. Moreover, the retention prediction using this new approach provided an acceptable level of accuracy on a used column exhibiting changes in ion-exchange capacity. PMID- 26860052 TI - Gradient enhanced-fluidity liquid hydrophilic interaction chromatography of ribonucleic acid nucleosides and nucleotides: A "green" technique. AB - A "green" hydrophilic interaction liquid chromatography (HILIC) technique for separating the components of mixtures with a broad range of polarities is illustrated using enhanced-fluidity liquid mobile phases. Enhanced-fluidity liquid chromatography (EFLC) involves the addition of liquid CO2 to conventional liquid mobile phases. Decreased mobile phase viscosity and increased analyte diffusivity results when a liquefied gas is dissolved in common liquid mobile phases. The impact of CO2 addition to a methanol:water (MeOH:H2O) mobile phase was studied to optimize HILIC gradient conditions. For the first time a fast separation of 16 ribonucleic acid (RNA) nucleosides/nucleotides was achieved (16min) with greater than 1.3 resolution for all analyte pairs. By using a gradient, the analysis time was reduced by over 100% compared to similar separations conducted under isocratic conditions. The optimal separation using MeOH:H2O:CO2 mobile phases was compared to MeOH:H2O and acetonitrile:water (ACN:H2O) mobile phases. Based on chromatographic performance parameters (efficiency, resolution and speed of analysis) and an assessment of the environmental impact of the mobile phase mixtures, MeOH:H2O:CO2 mixtures are preferred over ACN:H2O or MeOH:H2O mobile phases for the separation of mixtures of RNA nucleosides and nucleotides. PMID- 26860053 TI - A micro-perfusion bioreactor for on line investigation of ECM remodeling under hydrodynamic and biochemical stimulation. AB - Tissue-on-chip (TOC) systems aim at replicating complex biological dynamics in vitro with the potential either to improve the understanding of human biology or to develop more accurate therapeutic strategies. To replicate faithfully the intricate interrelationships between cells and their surrounding microenvironment, the three-dimensional (3D) tissue model must possess a responsive extracellular matrix (ECM). ECM remodeling plays a pivotal role in guiding cells and tissues functions and such aspect is somewhat denied during in vitro studies. For this purpose, we fabricated a micro-perfusion bioreactor capable to sustain the viability of 3D engineered tissue models recapitulating the process of the native ECM deposition and assembly. Engineered human dermis micro-tissue precursors (HD-MUTP) were used as building blocks to generate a final tissue. HD-MUTP were loaded in the perfusion space of the micro-perfusion bioreactor and, under the superimposition of different fluid dynamic regimes and biochemical stimulation, they synthesized new collagen proteins that were, then, assembled in the perfusion space forming a continuum of cells embedded in their own ECM. The micro-perfusion bioreactor was fabricated to allow the on-line monitoring of the oxygen consumption and the assembly of the newly formed collagen network via real time acquisition of the second harmonic generation (SHG) signal. The possibility to detect the collagen reorganization due to both fluid dynamic and biochemical stimulation, let us to define the optimal perfusion configuration in order to obtain a TOC system based on an endogenous and responsive ECM. PMID- 26860054 TI - Interactions between wheat Tubby-like and SKP1-like proteins. AB - Tubby proteins are highly conserved in a wide range of multicellular organisms. The Tubby gene family was first verified in obese mice. In plants, 11 Tubby genes have been identified in Arabidopsis, 14 in rice, and 11 in poplar. However, there is very little information about Tubby-like proteins in wheat. In this study, we identified four Tubby-like protein genes (TaTULP1-TaTULP4) in wheat. A comparison of the gene structure showed a conserved exon number pattern in TaTULPs, although the length of the introns differed. With the exception of TaTULP2, TaTULPs had four exons. To identify the chromosome localization of TaTULPs, BLASTn analyses were performed using the URGI database to predict the chromosomal location of TaTULP genes. TaTULP1, 2, 3 and 4 genes were localized on chromosomes 4, 5, 7 and 2. All TaTULPs harbor a Tubby domain in their C-terminal region and an F-box domain in the N terminus. We investigated protein-protein interactions between the F-box domain of TaTULPs and various wheat SKP1-like proteins (TaSKPs) using the yeast two-hybrid system. TaTULP1, TaTULP3 and TaTULP4 were found to interact with TaSKP1, TaSKP3 and TaSKP6, whereas TaTULP2 showed no interaction with TaSKP proteins. TaTULP proteins tagged with green fluorescent protein were targeted to the Golgi apparatus in plant cells. Our analysis of TaTULPs will aid in understanding the functions of TaTULPs in plants. PMID- 26860055 TI - The effects of a virtual reality treatment program for online gaming addiction. AB - BACKGROUND AND OBJECTIVE: Neuroimaging studies have demonstrated dysfunction in the brain reward circuit in individuals with online gaming addiction (OGA). We hypothesized that virtual reality therapy (VRT) for OGA would improve the functional connectivity (FC) of the cortico-striatal-limbic circuit by stimulating the limbic system. METHODS: Twenty-four adults with OGA were randomly assigned to a cognitive behavior therapy (CBT) group or VRT group. Before and after the four-week treatment period, the severity of OGA was evaluated with Young's Internet Addiction Scale (YIAS). Using functional magnetic resonance imaging, the amplitude of low-frequency fluctuation (ALFF) and FC from the posterior cingulate cortex (PCC) seed to other brain areas were evaluated. Twelve casual game users were also recruited and underwent only baseline assessment. RESULTS: After treatment, both CBT and VRT groups showed reductions in YIAS scores. At baseline, the OGA group showed a smaller ALFF within the right middle frontal gyrus and reduced FC in the cortico-striatal-limbic circuit. In the VRT group, connectivity from the PCC seed to the left middle frontal and bilateral temporal lobe increased after VRT. CONCLUSION: VRT seemed to reduce the severity of OGA, showing effects similar to CBT, and enhanced the balance of the cortico striatal-limbic circuit. PMID- 26860056 TI - Circulating free xeno-microRNAs - The new kids on the block. AB - The role of circulating free microRNAs (cfmiRNAs) as promising tools for cancer screening, prognosis and monitoring of anticancer therapies has been widely studied in the past decades. cfmiRNAs have all the characteristics of the perfect biomarkers owing high stability under storage and handling conditions and being detectable not only in plasma, but in almost all body fluids. Moreover, their levels in plasma are likely to resemble ones in the primary tumor. Recently, viral and plant miRNAs have been found in plasma of healthy individuals through deep sequencing technique, and subsequently the same ones were deregulated in patients. Growing body of literature is recently focusing on understanding the potential cross-kingdom regulation of human mRNAs by miRNAs most likely absorbed with food ingestion. In this article we will review the literature concerning the xenomiRs detected in plasma and their role in influencing cancer onset and progression. XenomiRs could potentially be used not only as early screening tool, but also for patients' prognosis. PMID- 26860058 TI - Monitoring the live to dead transition of bacteria during thermal stress by a multi-method approach. AB - Rapid microbiological methods to assess cell physiological properties of microorganisms are gaining interest in the elucidation of the effect of antimicrobial agents or physical inactivation. Fluorescent probes combined with flow cytometry or microplate assays provide information about cellular targets of chemical or physical stressors and help to clarify the underlying mode of action. In this work we exemplarily monitored the bacterial response of Listeria innocua, Staphylococcus aureus, Salmonella enterica and Escherichia coli to a mild thermal treatment by applying various methods to illustrate bacterial vital functions like the redox activity, membrane potential, esterase activity, efflux activity, glucose uptake, membrane integrity and plate counts. It was observed that some cellular properties are affected earlier than others. Respiration, glucose-uptake and pump activity were the most sensitive parameters, followed by the loss of membrane potential and membrane integrity. Unspecific esterase was found to be relatively resistant to mild heat exposure. This study shows that such a multi method approach is a suitable tool to monitor the impact of inactivation treatments on bacteria, providing information about the mode of action, the heterogeneity of populations, species-specific differences to stressors and valuable insight in vital functions beyond pure culturability. PMID- 26860057 TI - Reprogramming of Seed Metabolism Facilitates Pre-harvest Sprouting Resistance of Wheat. AB - Pre-harvest sprouting (PHS) is a worldwide problem for wheat production and transgene antisense-thioredoxin-s (anti-trx-s) facilitates outstanding resistance. To understand the molecular details of PHS resistance, we analyzed the metabonomes of the transgenic and wild-type (control) wheat seeds at various stages using NMR and GC-FID/MS. 60 metabolites were dominant in these seeds including sugars, organic acids, amino acids, choline metabolites and fatty acids. At day-20 post-anthesis, only malate level in transgenic wheat differed significantly from that in controls whereas at day-30 post-anthesis, levels of amino acids and sucrose were significantly different between these two groups. For mature seeds, most metabolites in glycolysis, TCA cycle, choline metabolism, biosynthesis of proteins, nucleotides and fatty acids had significantly lower levels in transgenic seeds than in controls. After 30-days post-harvest ripening, most metabolites in transgenic seeds had higher levels than in controls including amino acids, sugars, organic acids, fatty acids, choline metabolites and NAD(+). These indicated that anti-trx-s lowered overall metabolic activities of mature seeds eliminating pre-harvest sprouting potential. Post-harvest ripening reactivated the metabolic activities of transgenic seeds to restore their germination vigor. These findings provided essential molecular phenomic information for PHS resistance of anti-trx-s and a credible strategy for future developing PHS resistant crops. PMID- 26860059 TI - Improving the informed consent process in international collaborative rare disease research: effective consent for effective research. AB - The increased international sharing of data in research consortia and the introduction of new technologies for sequencing challenge the informed consent (IC) process, adding complexities that require coordination between research centres worldwide. Rare disease consortia present special challenges since available data and samples may be very limited. Thus, it is especially relevant to ensure the best use of available resources but at the same time protect patients' right to integrity. To achieve this aim, there is an ethical duty to plan in advance the best possible consent procedure in order to address possible ethical and legal hurdles that could hamper research in the future. Therefore, it is especially important to identify key core elements (CEs) to be addressed in the IC documents for international collaborative research in two different situations: (1) new research collections (biobanks and registries) for which information documents can be created according to current guidelines and (2) established collections obtained without IC or with a previous consent that does not cover all CEs. We propose here a strategy to deal with consent in these situations. The principles have been applied and are in current practice within the RD-Connect consortia - a global research infrastructure funded by the European Commission Seventh Framework program but forward looking in terms of issues addressed. However, the principles established, the lessons learned and the implications for future research are of direct relevance to all internationally collaborative rare-disease projects. PMID- 26860060 TI - Marfanoid-progeroid-lipodystrophy syndrome: a newly recognized fibrillinopathy. AB - We review six previous reports between 2000 and 2014 of seven unrelated patients with mutations in the FBN1 gene affecting function. All mutations occurred in exon 64 of the FBN1 gene. A distinctive phenotype consisting of partial manifestations of Marfan syndrome, a progeroid facial appearance, and clinical features of lipodystrophy was present in all individuals. We suggest that this previously unknown genotype/phenotype relationship constitutes a new fibrillinopathy for which the name marfanoid-progeroid-lipodystrophy syndrome would be appropriate. PMID- 26860061 TI - A method for analyzing multiple continuous phenotypes in rare variant association studies allowing for flexible correlations in variant effects. AB - For region-based sequencing data, power to detect genetic associations can be improved through analysis of multiple related phenotypes. With this motivation, we propose a novel test to detect association simultaneously between a set of rare variants, such as those obtained by sequencing in a small genomic region, and multiple continuous phenotypes. We allow arbitrary correlations among the phenotypes and build on a linear mixed model by assuming the effects of the variants follow a multivariate normal distribution with a zero mean and a specific covariance matrix structure. In order to account for the unknown correlation parameter in the covariance matrix of the variant effects, a data adaptive variance component test based on score-type statistics is derived. As our approach can calculate the P-value analytically, the proposed test procedure is computationally efficient. Broad simulations and an application to the UK10K project show that our proposed multivariate test is generally more powerful than univariate tests, especially when there are pleiotropic effects or highly correlated phenotypes. PMID- 26860062 TI - De novo PIK3R2 variant causes polymicrogyria, corpus callosum hyperplasia and focal cortical dysplasia. AB - We report an 8-year-old boy with a complex cerebral malformation, intellectual disability, and complex partial seizures. Whole-exome sequencing revealed a yet unreported de novo variant in the PIK3R2 gene that was recently associated with megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndrome and bilateral perisylvian polymicrogyria (BPP). Our patient showed cerebral abnormalities (megalencephaly, perisylvian polymicrogyria, and mega corpus callosum) that were consistent with these conditions. Imaging also showed right temporal anomalies suggestive of cortical dysplasia. Until now, only three variants (c.1117G>A (p.(G373R)), c.1126A>G (p.(K376E)) and c.1202T>C (p.(L401P))) affecting the SH2 domain of the PIK3R2 protein have been reported in MPPH and BPP syndromes. In contrast to the variants reported so far, the patient described herein exhibits the c.1669G>C (p.(D557H)) variant that affects a highly conserved residue at the interface with the PI3K catalytic subunit alpha. The phenotypic spectrum associated with variants in this gene and its pathway are likely to continue to expand as more cases are identified. PMID- 26860064 TI - Palisaded Neutrophilic Granulomatous Dermatitis in a Child with Juvenile Idiopathic Arthritis on Etanercept. AB - Palisaded neutrophilic granulomatous dermatitis (PNGD) is a rare neutrophilic dermatosis that may be associated with significant morbidity because of associated pruritus and pain. It is typically seen in adults with collagen vascular diseases, but may be associated with medications as well. PNGD is rarely reported in children. We describe a girl with polyarticular juvenile idiopathic arthritis who developed PNGD after administration of etanercept and demonstrated rapid and significant improvement upon treatment with topical triamcinolone 0.1% ointment. PMID- 26860063 TI - Association of the IGF1 gene with fasting insulin levels. AB - Insulin-like growth factor 1 (IGF-I) has been associated with insulin resistance. Genome-wide association studies (GWASs) of fasting insulin (FI) identified single nucleotide variants (SNVs) near the IGF1 gene, raising two hypotheses: (1) these associations are mediated by IGF-I levels and (2) these noncoding variants either tag other functional variants in the region or are directly functional. In our study, analyses including 5141 individuals from population-based cohorts suggest that FI associations near IGF1 are not mediated by IGF-I. Analyses of targeted sequencing data in 3539 individuals reveal a large number of novel rare variants at the IGF1 locus and show a FI association with a subset of rare nonsynonymous variants (PSKAT=5.7 * 10(-4)). Conditional analyses suggest that this association is partly explained by the GWAS signal and the presence of a residual independent rare variant effect (Pconditional=0.019). Annotation using ENCODE data suggests that the GWAS variants may have a direct functional role in insulin biology. In conclusion, our study provides insight into variation present at the IGF1 locus and into the genetic architecture underlying FI levels, suggesting that FI associations of SNVs near IGF1 are not mediated by IGF-I and suggesting a role for both rare nonsynonymous and common functional variants in insulin biology. PMID- 26860067 TI - Symmetry constraints during the development of anisotropic spinodal patterns. AB - Spinodal decomposition is a phase-separation phenomenon occurring at non equilibrium conditions. In isotropic materials, it is expected to improve the physical properties, in which modulated structures arise from a single system of spinodal waves. However, in anisotropic materials this process is controversial and not very well understood. Here, we report anisotropic spinodal decomposition patterns in single crystals of K-rich feldspar with macroscopic monoclinic 2/m symmetry. The periodicity of the spinodal waves at ~450 nm produces a blue iridescence, typical of the gemstone moonstone. Stripe patterns in the (010) plane, labyrinthine patterns in the (100) plane, and coexistence of the two patterns in the (110) plane are first resolved by scanning Rayleigh scattering microscopy. Two orthogonal systems of spinodal waves with the same periodicity are derived from the features and orientations of the patterns on the crystal surfaces. The orthogonality of the waves is related to the perpendicularity of the binary axis and the mirror plane. Thus, the spinodal patterns must be controlled by symmetry constraints during phase separation at early stages. Unusual and new properties could be developed in other anisotropic materials by thermal treatment inducing two orthogonal systems of periodic spinodal waves. PMID- 26860066 TI - High C3 photosynthetic capacity and high intrinsic water use efficiency underlies the high productivity of the bioenergy grass Arundo donax. AB - Arundo donax has attracted interest as a potential bioenergy crop due to a high apparent productivity. It uses C3 photosynthesis yet appears competitive with C4 grass biomass feedstock's and grows in warm conditions where C4 species might be expected to be that productive. Despite this there has been no systematic study of leaf photosynthetic properties. This study determines photosynthetic and photorespiratory parameters for leaves in a natural stand of A. donax growing in southern Portugal. We hypothesise that A. donax has a high photosynthetic potential in high and low light, stomatal limitation to be small and intrinsic water use efficiency unusually low. High photosynthetic rates in A. donax resulted from a high capacity for both maximum Rubisco (Vc,max 117 MUmol CO2 m( 2) s(-1)) and ribulose-1:5-bisphosphate limited carboxylation rate (Jmax 213 MUmol CO2 m(-2) s(-1)) under light-saturated conditions. Maximum quantum yield for light-limited CO2 assimilation was also high relative to other C3 species. Photorespiratory losses were similar to other C3 species under the conditions of measurement (25%), while stomatal limitation was high (0.25) resulting in a high intrinsic water use efficiency. Overall the photosynthetic capacity of A. donax is high compared to other C3 species, and comparable to C4 bioenergy grasses. PMID- 26860065 TI - Co-transfection of decorin and interleukin-10 modulates pro-fibrotic extracellular matrix gene expression in human tenocyte culture. AB - Extracellular matrix synthesis and remodelling are driven by increased activity of transforming growth factor beta 1 (TGF-beta1). In tendon tissue repair, increased activity of TGF-beta1 leads to progressive fibrosis. Decorin (DCN) and interleukin 10 (IL-10) antagonise pathological collagen synthesis by exerting a neutralising effect via downregulation of TGF-beta1. Herein, we report that the delivery of DCN and IL-10 transgenes from a collagen hydrogel system supresses the constitutive expression of TGF-beta1 and a range of pro-fibrotic extracellular matrix genes. PMID- 26860068 TI - An accessory skull suture mimicking a skull fracture. AB - This paper describes an investigation of the sudden and unexpected death of a five-and-a-half-month-old boy. As in every Dutch case of sudden unexpected death in infancy (SUDI), a multidisciplinary diagnostic approach was used. This included post-mortem radiography, showing a linear discontinuity of the parietal bone. Originally this was interpreted as a skull fracture, but autopsy indicated no signs of mechanical trauma. Instead the defect was defined as a unilateral accessory suture of the parietal bone. The initial erroneous diagnosis had severe adverse consequences and thus every health care professional or forensic specialist dealing with paediatric mechanical traumas should be cautious of this rare anomaly. PMID- 26860069 TI - Facial soft tissue thicknesses in the present Czech Population. AB - The aim of this study was to find any relation between soft facial tissue thickness (FSTT) and sex, age and asymmetry in the contemporary Czech population. The studied sample consisted of head CT scans of 102 adult Czech individuals between the ages of 21 and 83. Forty FSTTs were evaluated and analysed using PCA, Hotelling's T(2) test, LDA, the Kolmogorov-Smirnov test, MANOVA, the Kruskal Wallis test and Wilcoxon's paired test. The greatest sexual dimorphism was detected in the lower part of the face, which had discriminant power almost the same as the entire faces (approximately 80%). On the other hand, a significant influence of aging was shown, mostly in the area of the upper face (In females, twice as many landmarks displayed a significant influence, compared with males). The influence of asymmetry was confirmed in seven bilateral landmarks, five of them favouring the right side. PMID- 26860070 TI - Introduction of high nitrogen doped graphene as a new cationic carrier in electromembrane extraction. AB - This paper proposes for the first time, the use of high nitrogen doped graphene (HND-G) as a new cationic carrier for the enhancement of electromembrane extraction (EME) performance. Sensitivity of EME was improved by the modification of supported liquid membrane composition through the addition of HND-G into 1 octanol for the extraction of naproxen and sodium diclofenac as model acidic drugs. The comparison between HND-G-modified EME and conventional EME showed that HND-G could increase the overall partition coefficient of acidic drugs in the membrane due to the fact that HND-G acts as an ion pair reagent and there is an electrostatic interaction between positively charged HND-G and acidic drugs with negative charge. During the extraction, model acidic drugs migrated from a 10 mL aqueous sample solution (pH 9.6) through a thin layer of 1-octanol containing 0.6% w/v of HND-G that was impregnated in the pores of a hollow fiber, into a 30 MUL basic aqueous acceptor solution (pH 12.3) present in the lumen of the hollow fiber. Equilibrium extraction conditions were obtained after 16 min of operation with the whole assembly agitated at 1000 rpm. Under the optimized conditions, the enrichment factors were between 238 and 322 and also the LODs ranged from 0.1 to 0.7 ng/mL in different samples. Finally, the applicability of this method was evaluated by the extraction and determination of drugs of interest in real urine samples. PMID- 26860071 TI - Human mast cells costimulate T cells through a CD28-independent interaction. AB - Mast cells are innate immune cells usually residing in peripheral tissues, where they are likely to activate T-cell responses. Similar to other myeloid immune cells, mast cells can function as antigen-presenting cells. However, little is known about the capacity of human mast cells to costimulate CD4(+) T cells. Here, we studied the T-cell stimulatory potential of human mast cells. Peripheral blood derived mast cells were generated and cocultured with isolated CD4(+) T cells. In the presence of T-cell receptor triggering using anti-CD3, mast cells promoted strong proliferation of T cells, which was two- to fivefold stronger than the "T cell promoting capacity" of monocytes. The interplay between mast cells and T cells was dependent on cell-cell contact, suggesting that costimulatory molecules on the mast cell surface are responsible for the effect. However, in contrast to monocytes, the T-cell costimulation by mast cells was independent of the classical costimulatory molecule CD28, or that of OX40L, ICOSL, or LIGHT. Our data show that mast cells can costimulate human CD4(+) T cells to induce strong T cell proliferation, but that therapies aiming at disrupting the interaction of CD28 and B7 molecules do not inhibit mast cell mediated T-cell activation. PMID- 26860072 TI - Expansion of Safe Abortion Services in Nepal Through Auxiliary Nurse-Midwife Provision of Medical Abortion, 2011-2013. AB - INTRODUCTION: The termination of unwanted pregnancies up to 12 weeks' gestation became legal in Nepal in 2002. Many interventions have taken place to expand access to comprehensive abortion care services. However, comprehensive abortion care services remain out of reach for women in rural and remote areas. This article describes a training and support strategy to train auxiliary nurse midwives (ANMs), already certified as skilled birth attendants, as medical abortion providers and expand geographic access to safe abortion care to the community level in Nepal. METHODS: This was a descriptive program evaluation. Sites and trainees were selected using standardized assessment tools to determine minimum facility requirements and willingness to provide medical abortion after training. Training was evaluated via posttests and observational checklists. Service statistics were collected through the government's facility logbook for safe abortion services (HMIS-11). RESULTS: By the end of June 2014, medical abortion service had been expanded to 25 districts through 463 listed ANMs at 290 listed primary-level facilities and served 25,187 women. Providers report a high level of confidence in their medical abortion skills and considerable clinical knowledge and capacity in medical abortion. DISCUSSION: The Nepali experience demonstrates that safe induced abortion care can be provided by ANMs, even in remote primary-level health facilities. Post-training support for providers is critical in helping ANMs handle potential barriers to medical abortion service provision and build lasting capacity in medical abortion. PMID- 26860073 TI - Depression in dialysis patients. AB - Depression is the most common psychiatric illness in patients with end-stage renal disease (ESRD). The reported prevalence of depression in dialysis population varied from 22.8% (interview-based diagnosis) to 39.3% (self- or clinician-administered rating scales). Such differences were attributed to the overlapping symptoms of uraemia and depression. Systemic review and meta-analysis of observational studies showed that depression was a significant predictor of mortality in dialysis population. The optimal screening tool for depression in dialysis patients remains uncertain. The Beck Depression Inventory (BDI), Patient Health Questionnaire (PHQ) and Center for Epidemiologic Studies Depression Scale (CESD) have been validated for screening purposes. Patients who scored >=14 using BDI should be referred to a psychiatrist for early evaluation. Structured Clinical Interview for DSM disorders (SCID) remains the gold standard for diagnosis. Non-pharmacological treatment options include cognitive behavioural therapy and exercise training programs. Although frequent haemodialysis may have beneficial effects on patients' physical and mental well-being, it cannot and should not be viewed as a treatment of depression. Selective serotonin reuptake inhibitors (SSRIs) are generally effective and safe in ESRD patients, but most studies were small, non-randomized and uncontrolled. The European Renal Best Practice (ERBP) guideline suggests a trial of SSRI for 8 to 12 weeks in dialysis patients who have moderate-major depression. The treatment effect should be re evaluated after 12 weeks to avoid prolonging ineffective medication. This review will discuss the current understanding in the diagnosis and management of depression in dialysis patients. PMID- 26860074 TI - Letter to the editor. PMID- 26860075 TI - Double homozygous mutations (R275W and M432V) in the ParkinGene associated with late-onset Parkinson's disease. PMID- 26860076 TI - An order set and checklist improve physician transfusion ordering practices to mitigate the risk of transfusion-associated circulatory overload. AB - OBJECTIVES AND BACKGROUND: There are few studies of quality interventions to mitigate the risk of transfusion-associated circulatory overload (TACO). Our aim was to reduce TACO risk in patients admitted to internal medicine at our hospital, by addressing gaps in transfusion practice. MATERIALS AND METHODS: A 3 month baseline audit of red blood cell (RBC) transfusion orders was conducted. An intervention consisting of a transfusion order set and physician checklist was developed and implemented based on identified gaps, followed by a 3-month post intervention audit. Compliance with appropriateness criteria for RBC transfusion was ascertained, along with documentation of transfusion rate, diuretic usage and consent. RESULTS: A total of 97 transfusion orders from 68 inpatients and 95 orders from 62 inpatients were audited in the baseline and post-intervention groups, respectively. Compliance with appropriateness criteria was similar pre- and post-intervention (87 versus 85%, P = 0.81). Specification of transfusion rate improved (84 versus 98%, P < 0.01), and diuretics were appropriately ordered more frequently for patients with TACO risk factors (37 versus 64%, P < 0.01). Timing of diuretics shifted from between or post-transfusion to pre-transfusion (35 versus 86%, P < 0.01), without increases in hypokalemia or acute kidney injury. No case of TACO was observed during the study. Documentation of specific risks discussed during consent discussion improved (4 versus 23%, P < 0.01). CONCLUSION: A checklist and order set are tools that can improve the quality of transfusion orders by increasing the judicious use of pre-transfusion diuretics and augmenting the specification of transfusion rate. These interventions could be adapted to electronic order formats to improve transfusion safety. PMID- 26860077 TI - In-chain functionalized polymer induced assembly of nanoparticles: toward materials with tailored properties. AB - We adopt a molecular dynamics simulation method to describe the self-assembly of nanoparticles in in-chain functionalized polymers. In such novel systems, the organization of nanoparticles is governed by the interplay of the intrinsic attractions between nanoparticles and the entropy of redistributing the functionalized polymers that are adsorbed on the nanoparticles. Our simulations also demonstrate that this approach to nanoparticle assembly enables considerable control for the creation of polymer nanocomposites with tailored properties. PMID- 26860078 TI - beta-Catenin signaling pathway regulates cisplatin resistance in lung adenocarcinoma cells by upregulating Bcl-xl. AB - The Wnt/beta-catenin signaling pathway has been reported to regulate cisplatin resistance in several types of cancer cell. The present study aimed to investigate the role and underlying mechanism of Wnt/beta-catenin signaling in cisplatin resistance of lung adenocarcinoma cells. Wild-type and cisplatin resistant A549 human lung adenocarcinoma cells (A549/WT and A549/CDDP, respectively) were cultured in vitro and exposed to different cisplatin concentrations. Cells were incubated with 10 mM lithium chloride (LiCl) to activate beta-catenin signaling. Cell proliferation was determined using the MTS assay. Cell apoptosis was evaluated using Annexin V/propidium iodide double staining, followed by flow cytometry. beta-catenin was knocked down using small interfering RNA (siRNA). The intracellular distribution of beta-catenin was determined by immunocytochemistry, and the mRNA and protein expressions of target genes were examined by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. beta-catenin and B-cell lymphoma extra large (Bcl-xl) were significantly upregulated in A549/CDDP cells compared with A549/WT cells (P<0.05). LiCl reduced the sensitivity of A549/WT cells to cisplatin (P<0.01); and upregulated, increased phosphorylation (P<0.05) and enhanced nuclear translocation of beta-catenin. LiCl also significantly elevated the mRNA and protein expression levels of Bcl-xl (P<0.05). Notably, silencing of beta-catenin with siRNA decreased the mRNA and protein expression of Bcl-xl, and sensitized A549/WT cells to cisplatin (P<0.01). The findings of the current study suggest that upregulation of beta-catenin signaling may contribute to cisplatin resistance in lung adenocarcinoma cells by upregulating Bcl-xl. Therefore, molecular targeting of Wnt/beta-catenin signaling may sensitize lung cancer cells to cisplatin. PMID- 26860081 TI - Multiple antibiotic resistance index, fitness and virulence potential in respiratory Pseudomonas aeruginosa from Jamaica. AB - Respiratory infections are common causes of morbidity and mortality worldwide. We sought to assess the multiple antibiotic resistance (MAR) index, fitness and virulence potential in Pseudomonas aeruginosa from patients with lower respiratory tract infections. Isolates were assessed for antimicrobial susceptibility, in vitro competitive fitness, and pigment, elastase and rhamnolipid production. Oxidative stress tolerance was determined on both planktonic and biofilm cells, and virulence potential was tested in a plant model. Mean MAR index for isolates was 0.34 (range 0.17-0.50). Whilst isolates exhibited good biofilm formation in the presence of ciprofloxacin, there was no significant difference in biofilm production over the concentration range assessed. Several drug-resistant strains were out-competed by a susceptible strain even in the presence of antibiotic. H2O2 exerted a greater oxidative stress than tert-butyl-hydroperoxide and, as expected, biofilms were more resistant than planktonic cells. Whilst most (81 %) isolates were pigmented there was no significant difference between pigmented and non-pigmented isolates when elastolytic activity was compared (P>0.05). More than half of the isolates produced the quorum sensing mediator rhamnolipid and infection of the plant model by bacteria occurred whether elastase or rhamnolipid was present or absent. These data suggest that non-pigmented strains of P. aeruginosa might pose an equally significant microbiological threat as pigmented strains even though pigment production appeared to be strongly associated with elastase expression. Whilst dual expression of elastase and rhamnolipid by these bacteria would cause severe tissue damage (as seen in the plant model), non-production of either does not prevent bacteria from causing serious infection. PMID- 26860079 TI - MicroRNA-194 is a Marker for Good Prognosis in Clear Cell Renal Cell Carcinoma. AB - Clear cell renal cell carcinoma (ccRCC) is the most prevalent adult kidney cancer. Prognostic markers are needed to guide patient management toward aggressive versus more conservative approaches, especially for small tumors <=4 cm. miR-194 was reported to be downregulated in several cancers and is involved in epithelial to mesenchymal transition. We evaluated miR-194 as a prognostic marker in ccRCC. In a cohort of 234 patients with primary ccRCC, we correlated miR-194 expression level with multiple clinicopathological features including disease-free and overall survival, tumor size, clinical stage, and histological grade. Our results shows a stepwise decrease in miR-194 expression from normal kidney to primary ccRCC (P = 0.0032) and a subsequent decrease from primary to metastatic lesions. Additionally, patients with higher miR-194 expression has significantly longer disease-free survival (P = 0.041) and overall survival (P = 0.031) compared to those with lower expression. In multivariate analysis, miR-194 positive tumors retain significance in disease-free survival and overall survival, suggesting miR-194 is an independent marker for good prognosis in ccRCC. Moreover, miR-194 is a marker for good prognosis for patients with small renal masses (P = 0.014). These findings were validated on an independent data set from The Cancer Genome Atlas. We also compared miR-194 expression between RCC subtypes. ccRCC had the highest levels, whereas chromophobe RCC and oncocytoma had comparable lower levels. Target prediction coupled with pathway analysis show that miR-194 is predicted to target key molecules and pathways involved in RCC progression. miR-194 represents a prognostic biomarker in ccRCC. PMID- 26860080 TI - Andrographolide attenuates LPS-stimulated up-regulation of C-C and C-X-C motif chemokines in rodent cortex and primary astrocytes. AB - BACKGROUND: Andrographolide is the major bioactive compound isolated from Andrographis paniculata, a native South Asian herb used medicinally for its anti inflammatory properties. In this study, we aimed to assess andrographolide's potential utility as an anti-neuroinflammatory therapeutic. METHODS: The effects of andrographolide on lipopolysaccharide (LPS)-induced chemokine up-regulation both in mouse cortex and in cultured primary astrocytes were measured, including cytokine profiling, gene expression, and, in cultured astrocytes, activation of putative signaling regulators. RESULTS: Orally administered andrographolide significantly attenuated mouse cortical chemokine levels from the C-C and C-X-C subfamilies. Similarly, andrographolide abrogated a range of LPS-induced chemokines as well as tumor necrosis factor (TNF)-alpha in astrocytes. In astrocytes, the inhibitory actions of andrographolide on chemokine and TNF-alpha up-regulation appeared to be mediated by nuclear factor-kappaB (NF-kappaB) or c Jun N-terminal kinase (JNK) activation. CONCLUSIONS: These results suggest that andrographolide may be useful as a therapeutic for neuroinflammatory diseases, especially those characterized by chemokine dysregulation. PMID- 26860082 TI - Thoracic dysfunction in whiplash-associated disorders: a systematic review and meta-analysis protocol. AB - BACKGROUND: Whiplash-associated disorder (WAD) research has largely focused on the neck, yet symptoms often include other areas. The prevalence of acute thoracic spine pain is reported ~66 %, which is perhaps unsurprising given the mechanism of injury involves a forceful loading/eccentric contraction of posterior thoracic structures such as the trapezius. Many individuals with WAD experience disability and pain beyond normal tissue healing time, termed chronic WAD. With the thoracic spine contributing to neck mobility, and 23 % of individuals complaining of thoracic pain 1 year post injury, it is time to look beyond the neck to fully understand the anatomical dysfunction in WAD. METHODS/DESIGN: A systematic review protocol has been designed and will be reported in line with Preferred Reporting Items for Systematic Reviews and Meta Analyses Protocols (PRISMA-P). A sensitive topic-based search strategy is planned from inception to the current date. Databases, grey literature and registers will be searched using terms and keywords derived from a scoping search. Two reviewers will independently search information sources, assess studies for inclusion and extract data. A third reviewer will check for accuracy. Data to be extracted include summary data: sample size and characteristics, timescales to reflect disorder state, patient-reported or performance-based measure and findings. Risk of bias within studies will be assessed using the Newcastle-Ottawa Scale. Quantitative meta-analysis approach will be used for homogenous data and where appropriate presented using subgroups. All other results will be presented using narrative summaries. Subgroups will, where possible, be based on patient-reported or performance-based measure of dysfunction and/or stage of condition (acute/sub acute or chronic). Strength of the overall body of evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). DISCUSSION: This is the first study to bring together evidence of thoracic dysfunction post whiplash and provide new insights into the scope and nature of thoracic dysfunction in WAD. With current management options being largely focused to a primary neck complaint and many patients going to become chronic in their presentations, this review may stimulate research and clinical interest in a largely under investigated, yet anatomically and kinematically related, spinal region. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015026983. PMID- 26860083 TI - TLK1B mediated phosphorylation of Rad9 regulates its nuclear/cytoplasmic localization and cell cycle checkpoint. AB - BACKGROUND: The Tousled like kinase 1B (TLK1B) is critical for DNA repair and survival of cells. Upon DNA damage, Chk1 phosphorylates TLK1B at S457 leading to its transient inhibition. Once TLK1B regains its kinase activity it phosphorylates Rad9 at S328. In this work we investigated the significance of this mechanism by overexpressing mutant TLK1B in which the inhibitory phosphorylation site was eliminated. RESULTS AND DISCUSSION: These cells expressing TLK1B resistant to DNA damage showed constitutive phosphorylation of Rad9 S328 that occurred even in the presence of hydroxyurea (HU), and this resulted in a delayed checkpoint recovery. One possible explanation was that premature phosphorylation of Rad9 caused its dissociation from 9-1-1 at stalled replication forks, resulting in their collapse and prolonged activation of the S phase checkpoint. We found that phosphorylation of Rad9 at S328 results in its dissociation from chromatin and redistribution to the cytoplasm. This results in double stranded breaks formation with concomitant activation of ATM and phosphorylation of H2AX. Furthermore, a Rad9 (S328D) phosphomimic mutant was exclusively localized to the cytoplasm and not the chromatin. Another Rad9 phosphomimic mutant (T355D), which is also a site phosphorylated by TLK1, localized normally. In cells expressing the mutant TLK1B treated with HU, Rad9 association with Hus1 and WRN was greatly reduced, suggesting again that its phosphorylation causes its premature release from stalled forks. CONCLUSIONS: We propose that normally, the inactivation of TLK1B following replication arrest and genotoxic stress functions to allow the retention of 9-1-1 at the sites of damage or stalled forks. Following reactivation of TLK1B, whose synthesis is concomitantly induced by genotoxins, Rad9 is hyperphosphorylated at S328, resulting in its dissociation and inactivation of the checkpoint that occurs once repair is complete. PMID- 26860084 TI - Concept of defensive medicine and litigation among Sudanese doctors working in obstetrics and gynecology. AB - BACKGROUND: Obstetrics and gynaecology always has reputation for being a highly litigious. The field of obstetrics and gynaecology is surrounded by different circumstances that stimulate the doctors to practice defensive medicine. METHODS: This study was directed to assess the extent and the possible effect of defensive medicine phenomenon (in term of knowledge and prevalence) on medical decision making among different grades of obstetric and gynaecologic Sudanese doctors, and to determine any experience of medical litigations with respect to sources and factors associated with it (in term of area of work, characteristics of the area at which the doctors worked, professionalism, hospitals systems...ect). RESULTS: A total of 117 doctors were approached, their distribution according to job description was as follow: consultants (42.7%, 50?117) registrars (34.2%, 40?117) and specialists (23.1%, 27?117). The majority 89.7% had the impression that litigation against doctors are increasing and 27.6% had a direct experience of litigation. In this study less than one half (42.7%) of the surveyed doctors knew the concept of defensive medicine and 71.8% reported practicing one or another form of defensive medicine. The different sources of the litigations reported by the doctors included: maternal death (n = 15), perinatal death (n = 5), other {misdiagnosis, intra-uterine fetal death, uterine perforation, rupture uterus} (n = 4), fetal distress (n = 3), injury to viscera (n = 3) and shoulder dystocia (n = 2). In this study the experience of medical litigation was significantly observed among those who worked in area of blame culture (90.6% Vs 56.5%, P = 0.000). In logistic regression model, there was no significant difference between those who knew the concept of defence medicine and those who didn't. CONCLUSION: There should be strategic plan to reduce the practice of defensive medicine and medical litigation against doctors. PMID- 26860085 TI - Erratum to: 'Intake of Macro- and Micronutrients in Danish Vegans'. PMID- 26860086 TI - Comorbid epilepsy in Finnish patients with adult-onset Huntington's disease. AB - BACKGROUND: Seizures are common in juvenile Huntington's disease (HD), but considered to be rare in adult-onset HD. We studied the occurrence of epilepsy and seizures in a nationwide cohort of Finnish patients with adult-onset HD. METHODS: Patients with HD and their diagnoses of epilepsy or seizures were identified by a search into a nationwide registry. Cases were verified in a subsequent review of patient charts. RESULTS: Three out of 114 HD patients alive on prevalence date had been diagnosed with epilepsy giving a prevalence of 2.6% (95% CI, 0.6-7.5). In addition, one patient with a single unprovoked seizure, one patient with a medication-induced seizure and two patients with transient nonspecific attacks were identified. Epilepsy was not associated with clinical severity of HD and seizures were controlled with antiepileptic medications (AEDs). Generalized tonic-clonic seizures (GTCs) were the most common seizure type. CONCLUSIONS: Prevalence of epilepsy is similar in patients with adult-onset HD compared to general population. Seizures are easily controlled with AEDs. PMID- 26860087 TI - Examining the Influence of Phosphorylation on Peptide Ion Structure by Ion Mobility Spectrometry-Mass Spectrometry. AB - Ion mobility spectrometry-mass spectrometry (IMS-MS) techniques are used to study the general effects of phosphorylation on peptide structure. Cross sections for a library of 66 singly phosphorylated peptide ions from 33 pairs of positional isomers, and unmodified analogues were measured. Intrinsic size parameters (ISPs) derived from these measurements yield calculated collision cross sections for 85% of these phosphopeptide sequences that are within +/-2.5% of experimental values. The average ISP for the phosphoryl group (0.64 +/- 0.05) suggests that in general this moiety forms intramolecular interactions with the neighboring residues and peptide backbone, resulting in relatively compact structures. We assess the capability of ion mobility to separate positional isomers (i.e., peptide sequences that differ only in the location of the modification) and find that more than half of the isomeric pairs have >1% difference in collision cross section. Phosphorylation is also found to influence populations of structures that differ in the cis/trans orientation of Xaa-Pro peptide bonds. Several sequences with phosphorylated Ser or Thr residues located N-terminally adjacent to Pro residues show fewer conformations compared to the unmodified sequences. PMID- 26860088 TI - Conformational Analysis of Proteins in Highly Concentrated Solutions by Dialysis Coupled Hydrogen/Deuterium Exchange Mass Spectrometry. AB - When highly concentrated, an antibody solution can exhibit unusual behaviors, which can lead to unwanted properties, such as increased levels of protein aggregation and unusually high viscosity. Molecular modeling, along with many indirect biophysical measurements, has suggested that the cause for these phenomena can be due to short range electrostatic and/or hydrophobic protein protein interactions. Hydrogen/deuterium exchange mass spectrometry (HDX-MS) is a useful tool for investigating protein conformation, dynamics, and interactions. However, "traditional" continuous dilution labeling HDX-MS experiments have limited utility for the direct analysis of solutions with high concentrations of protein. Here, we present a dialysis-based HDX-MS (di-HDX-MS) method as an alternative HDX-MS labeling format, which takes advantage of passive dialysis rather than the classic dilution workflow. We applied this approach to a highly concentrated antibody solution without dilution or significant sample manipulation, prior to analysis. Such a method could pave the way for a deeper understanding of the unusual behavior of proteins at high concentrations, which is highly relevant for development of biopharmaceuticals in industry. Graphical Abstract ?. PMID- 26860089 TI - Individual behavioral and neurochemical markers of unadapted decision-making processes in healthy inbred mice. AB - One of the hallmarks of decision-making processes is the inter-individual variability between healthy subjects. These behavioral patterns could constitute risk factors for the development of psychiatric disorders. Therefore, finding predictive markers of safe or risky decision-making is an important challenge for psychiatry research. We set up a mouse gambling task (MGT)-adapted from the human Iowa gambling task with uncertain contingencies between response and outcome that furthermore enables the emergence of inter-individual differences. Mice (n = 54) were further individually characterized for locomotive, emotional and cognitive behavior. Individual basal rates of monoamines and brain activation after the MGT were assessed in brain regions related to reward, emotion or cognition. In a large healthy mice population, 44 % showed a balanced strategy with limited risk taking and flexible choices, 29 % showed a safe but rigid strategy, while 27 % adopted risky behavior. Risky mice took also more risks in other apparatus behavioral devices and were less sensitive to reward. No difference existed between groups regarding anxiety, working memory, locomotion and impulsivity. Safe/rigid mice exhibited a hypoactivation of prefrontal subareas, a high level of serotonin in the orbitofrontal cortex combined with a low level of dopamine in the putamen that predicted the emergence of rigid behavior. By contrast, high levels of dopamine, serotonin and noradrenalin in the hippocampus predicted the emergence of more exploratory and risky behaviors. The coping of C57bl/6J mice in MGT enables the determination of extreme patterns of choices either safe/rigid or risky/flexible, related to specific neurochemical and behavioral markers. PMID- 26860090 TI - Internal plate fixation versus plaster in displaced complete articular distal radius fractures, a randomised controlled trial. AB - BACKGROUND: Of all distal radius fractures, 25 % are complete articular fractures (AO/OTA type C fractures). Two thirds of those fractures are displaced and require reduction. According to several International Guidelines, adequately reduced intra-articular distal radius fractures are best treated non-operatively with plaster immobilisation, while surgical fixation is suggested only when the articular step exceeds 2 mm after reduction. However, these recommendations are based on studies that did not differentiate between intra- and extra-articular distal radius fractures. Thus, no clear consensus about the best treatment for patients with displaced intra-articular distal radius fractures can be reached. Despite the lack of evidence, an increase in internal fixation of intra-articular distal radius fractures has been observed over the last decade. The aim of this study is to determine the difference in functional outcome following open reduction and plate fixation compared with non-operative treatment with closed reduction and plaster immobilisation in patients with a displaced intra articular distal radius fracture. METHODS/DESIGN: This multicentre randomised controlled trial will randomise between open reduction and internal plate fixation (intervention group) and closed reduction and plaster immobilisation (control group). All consecutive adult patients from 18 to 65 years with a displaced intra articular distal radius fracture (AO/OTA type C), which has been adequately reduced at the Emergency Department according to the Dutch National Guidelines, are eligible for inclusion in this study. The primary outcome is function and pain of the wrist assessed with the Patient-Rated Wrist Evaluation score (PRWE). Secondary outcomes are the Disability of the Arm, Shoulder and Hand score (DASH), pain, quality of life (SF-36), range of motion, grip strength, radiological parameters, complications, crossovers and cost-effectiveness of both treatments. A total of 90 patients will be included in this study. DISCUSSION: Although displaced intra-articular distal radius fractures are common, there is still no evidence on the optimal treatment for these fractures in patients aged 18 to 65 years. Therefore we aim to determine the difference in functional outcome between open reduction and plate fixation and closed reduction and plaster immobilisation. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov ( NCT02651779 ) on January 4(th) 2016. PMID- 26860091 TI - Primary familial brain calcification in a Norwegian family, caused by a novel SLC20A2 gene mutation. PMID- 26860092 TI - Prevalence and symptoms of intracranial arachnoid cysts: a population-based study. AB - To investigate the prevalence of intracranial arachnoid cysts in a large population-based sample. We also aimed to assess the association between arachnoid cysts and cognitive impairment, depression, epilepsy, headache, dizziness, previous head trauma, hip fractures, and mortality. A population-based cohort and nested case-control study. The sample comprised representative populations (n = 1235) aged >= 70 years. All participants underwent baseline neuropsychiatric examinations, including computed tomography (CT) of the brain, between 1986 and 2000. All CT scans were examined for arachnoid cysts. Headache, dizziness, history of head trauma, dementia, depression, epilepsy, and hip fracture were assessed using data from clinical examinations, interviews and the Swedish hospital discharge register. Cognition was assessed using the Mini-Mental Status Examination, and depressive symptoms using the Montgomery-Asberg Depression Rating Scale. Date of death was obtained from the National Swedish Death Registry. The prevalence of arachnoid cysts was 2.3 % (n = 29), with no significant difference between men and women. Probands with and without cysts had the same frequency of headache, dizziness, previous head trauma, cognitive impairment, and depressive symptoms. Furthermore, there were no differences regarding the prevalence of dementia, depression, epilepsy, or previous hip fracture. Arachnoid cysts were not associated with increased mortality. Arachnoid cysts are common incidental finding, with the same rate in men and women, and are probably asymptomatic. The lack of relation with symptoms like headache, dizziness and cognitive impairment suggest caution in ascribing symptoms to incidentally discovered arachnoid cysts and a restrictive attitude to treatment. PMID- 26860093 TI - Visual field impairment captures disease burden in multiple sclerosis. AB - Monitoring disease burden is an unmeet need in multiple sclerosis (MS). Identifying patients at high risk of disability progression will be useful for improving clinical-therapeutic decisions in clinical routine. To evaluate the role of visual field testing in non-optic neuritis eyes (non-ON eyes) as a biomarker of disability progression in MS. In 109 patients of the MS-VisualPath cohort, we evaluated the association between visual field abnormalities and global and cognitive disability markers and brain and retinal imaging markers of neuroaxonal injury using linear regression models adjusted for sex, age, disease duration and use of disease-modifying therapies. We evaluated the risk of disability progression associated to have baseline impaired visual field after 3 years of follow-up. Sixty-two percent of patients showed visual field defects in non-ON eyes. Visual field mean deviation was statistically associated with global disability; brain (normalized brain parenchymal, gray matter volume and lesion load) and retinal (peripapillary retinal nerve fiber layer thickness and macular ganglion cell complex thickness) markers of neuroaxonal damage. Patients with impaired visual field had statistically significative greater disability, lower normalized brain parenchymal volume and higher lesion volume than patients with normal visual field testing. MS patients with baseline impaired VF tripled the risk of disability progression during follow-up [OR = 3.35; 95 % CI (1.10-10.19); p = 0.033]. The association of visual field impairment with greater disability and neuroaxonal injury and higher risk of disability progression suggest that VF could be used to monitor MS disease burden. PMID- 26860094 TI - Imaging assessment of patellar instability and its treatment in children and adolescents. AB - Transient patellar dislocation is a common entity in children and adolescents, characterized by lateral dislocation of the patella, usually with spontaneous reduction. Many predisposing conditions have been described, including trochlear dysplasia, excessive lateral patellar tilt, patella alta and lateralization of the tibial tuberosity. Associated injuries are bone bruises of the patella and lateral femoral condyle, tears of the medial retinaculum that include the medial patellofemoral ligament (MPFL), tears of the vastus medialis obliquus muscle, injuries of articular cartilage, and intra-articular bodies. Children who are refractory to conservative management, have a large cartilage defect, or are at substantial risk for recurrent dislocations are candidates for surgical procedures to prevent future dislocations. Procedures can include MPFL repair or reconstruction, tibial tubercle repositioning and lateral retinacular release. The purpose of this review is to illustrate the imaging findings of transient patellar dislocation in the acute setting, the normal imaging appearance after surgical intervention, and post-surgical complications. PMID- 26860095 TI - Distress experienced during pediatric VCUGs - a granular, prospective assessment using the brief behavioral distress scale. AB - BACKGROUND: In spite of decades of experience with the procedure, controversy persists as to the overall distress experienced by children and the routine need for sedation in children undergoing voiding cystourethrograms (VCUG). Many studies have attempted to address these issues, often divided into one camp that champions routine sedation while another group believes that pretest preparation is often all that is needed. At the root of these issues are some of the limitations of previous studies as most incorporate inherently subjective parental questionnaires to determine distress levels rather than using an objective, unbiased observer. OBJECTIVE: The objective of this study is to use a validated and reliable tool (the brief behavioral distress scale) to objectively evaluate the distress experienced during VCUGs. MATERIALS AND METHODS: A prospective study of 26 children (ages 3-7 years old) was performed by the pediatric radiology department at a large urban academic medical center. Patients were evaluated for distress during 12 separate VCUG steps beginning with the patient entering the room and ending with the clothing being replaced at study completion. RESULTS: Using a general linear model (repeated measures analysis of variance (ANOVA)), significant distress was identified during two phases of the examination, catheter insertion (P-values ranging <0.001-0.19) and the full bladder phase (P-values ranging 0.005-0.043). The mean distress score for catheter insertion (mean: 1.38, standard deviation [SD]: 1.098) was nearly three times higher than the next most distressful step, i.e. full bladder (mean: 0.65, SD: 0.745). Additionally, entering the room was perceived as significantly more distressing than the catheter out (P = 0.016) and clothing replacement phase (P = 0.006). CONCLUSION: We find that despite there being significantly increased distress during the catheter insertion and full bladder phases, the distress levels during VCUGs are markedly less than in previous reports. Even the most distressful stage, catheterization, was less stressful than previously reported with levels closer to that of minor distress evinced by comfort-seeking behavior from a parent rather than more significant distress resulting in screaming. Our findings corroborate and expand on the conclusion of the effectiveness of pretest preparation and child life specialist involvement. PMID- 26860096 TI - Effects of narrow-base walking and dual tasking on gait spatiotemporal characteristics in anterior cruciate ligament-injured adults compared to healthy adults. AB - PURPOSE: The present experiment was conducted to examine the hypothesis that challenging control through narrow-base walking and/or dual tasking affects ACL injured adults more than healthy control adults. METHODS: Twenty male ACL-injured adults and twenty healthy male adults walked on a treadmill at a comfortable speed under two base-of-support conditions, normal-base versus narrow-base, with and without a cognitive task. Gait patterns were assessed using mean and variability of step length and mean and variability of step velocity. Cognitive performance was assessed using the number of correct counts in a backward counting task. RESULTS: Narrow-base walking resulted in a larger decrease in step length and a more pronounced increase in variability of step length and of step velocity in ACL-injured adults than in healthy adults. For most of the gait parameters and for backward counting performance, the dual-tasking effect was similar between the two groups. CONCLUSIONS: ACL-injured adults adopt a more conservative and more unstable gait pattern during narrow-base walking. This can be largely explained by deficits of postural control in ACL-injured adults, which impairs gait under more balance-demanding conditions. The observation that the dual-tasking effect did not differ between the groups may be explained by the fact that walking is an automatic process that involves minimal use of attentional resources, even after ACL injury. Clinicians should consider the need to include aspects of terrain complexity, such as walking on a narrow walkway, in gait assessment and training of patients with ACL injury. LEVEL OF EVIDENCE: III. PMID- 26860097 TI - A comparison of revision and rerupture rates of ACL reconstruction between autografts and allografts in the skeletally immature. AB - PURPOSE: Anterior cruciate ligament reconstructions (ACLRs) in skeletally immature patients are increasing. The purpose of this study is to describe the demographics, graft usage, revision, and re-operation rates in skeletally immature ACLRs in the Kaiser Permanente healthcare system. METHODS: Skeletally immature patients (<17.0 years old with open physes) were identified using the Kaiser Permanente ACLR registry. Multi-ligament reconstructions and physeal sparing ACLRs were excluded. Aseptic revision and same-knee re-operation were the outcomes of interest. Exposure of interest was graft type; bone-patellar-tendon bone (BPTB) autograft, hamstring autograft, and any type of allograft. Age, gender, body mass index (BMI), and race were evaluated as confounders. Cox proportional hazard models stratified by surgeon were used to analyse the risk of revision and re-operation. RESULTS: A total of 534 primary ACLR cases were evaluated with a mean follow-up of 2.9 years. The majority were hamstring autografts (n = 388, 72.7%), male (n = 339, 63.9%), and White (n = 232, 43.4%). Median age was 14.9 years, and median BMI was 21.9 kg/m(2). There were 44 (8.2%) aseptic revisions and 48 (9.0%) same-knee re-operations. The incidence rate for revision was BPTB autograft 5.5%, hamstring autograft 7.5%, and allograft 13.2%. After adjusting for confounders and surgeon clustering effect, the risk of aseptic revision and revision between allograft and hamstring autograft did not reach statistical significance. CONCLUSION: Graft selection differs in skeletally immature patients with a preponderance of surgeries being performed with hamstring tendon autografts. High revision rates were identified for all graft types used, though differences in revision rates across different graft types did not reach statistical significance. Surgeons should be aware of high rates of revision in this skeletally immature young population, although type of graft used did not appear to make a difference. LEVEL OF EVIDENCE: III. PMID- 26860098 TI - Validation of a virtual reality-based simulator for shoulder arthroscopy. AB - PURPOSE: This study was to determine face and construct validity of a new virtual reality-based shoulder arthroscopy simulator which uses passive haptic feedback. METHODS: Fifty-one participants including 25 novices (<20 shoulder arthroscopies) and 26 experts (>100 shoulder arthroscopies) completed two tests: for assessment of face validity, a questionnaire was filled out concerning quality of simulated reality and training potential using a 7-point Likert scale (range 1-7). Construct validity was tested by comparing simulator metrics (operation time in seconds, camera and grasper pathway in centimetre and grasper openings) between novices and experts test results. RESULTS: Overall simulated reality was rated high with a median value of 5.5 (range 2.8-7) points. Training capacity scored a median value of 5.8 (range 3-7) points. Experts were significantly faster in the diagnostic test with a median of 91 (range 37-208) s than novices with 1177 (range 81-383) s (p < 0.0001) and in the therapeutic test 102 (range 58-283) s versus 229 (range 114-399) s (p < 0.0001). Similar results were seen in the other metric values except in the camera pathway in the therapeutic test. CONCLUSION: The tested simulator achieved high scores in terms of realism and training capability. It reliably discriminated between novices and experts. Further improvements of the simulator, especially in the field of therapeutic arthroscopy, might improve its value as training and assessment tool for shoulder arthroscopy skills. LEVEL OF EVIDENCE: II. PMID- 26860099 TI - Does post-operative knee awareness differ between knees in bilateral simultaneous total knee arthroplasty? Predictors of high or low knee awareness. AB - PURPOSE: To evaluate the difference in post-operative knee awareness between knees in patients undergoing bilateral simultaneous total knee arthroplasty (TKA) and to assess factors predicting high or low knee awareness. METHODS: This study was conducted on 99 bilateral simultaneous TKAs performed at our institution from 2008 to 2012. All patients received one set of questionnaires [Forgotten Joint Score (FJS) and Oxford Knee Score (OKS)] for each knee. Based on the FJS, the patients' knees were divided into two groups: "best" and "worst" knees. The median of the absolute difference in FJS and OKS within each patient was calculated. Multivariate linear regression was performed to identify factors affecting FJS. RESULTS: The difference between knees was 1 point (CI 0-5) for the FJS and 1 point (CI 0-2) for the OKS. The FJS for females increased (decreasing awareness) with increasing age. Males had the highest FJS (lowest awareness) at the age of 67. An increase in the FJS (lower knee awareness) of 12.0 points was found for Kellgren-Lawrence (K-L) grades 3 + 4 compared with K-L grades 1 + 2. A preoperative anatomical alignment of 3 degrees valgus resulted in the lowest FJS (highest knee awareness) with decreasing knee awareness for decreasing tibio femoral angles. Post-operative alignment did not significantly affect FJS. CONCLUSION: Knee awareness did not differ significantly between the "best" and the "worst" knee. Bilateral simultaneous TKA can be performed without compromising the result in one of the knees. Knee awareness after primary TKA was influenced by age, gender, preoperative knee alignment, and severity of OA. LEVEL OF EVIDENCE: III. PMID- 26860100 TI - Comparison of the recurrence risk of parameniscal cysts between patients treated with arthroscopic excision and arthroscopic decompression techniques. AB - PURPOSE: To compare the recurrence risk of parameniscal cysts between arthroscopic meniscectomy with open cystectomy (arthroscopic excision) and entirely arthroscopic techniques with intra-articular cyst decompression (arthroscopic decompression). METHODS: A retrospective longitudinal study was conducted at a medical centre in Taiwan between 2002 and 2012. Patients with symptomatic parameniscal cysts undergoing either arthroscopic excision or arthroscopic decompression were included. Parameniscal cyst recurrence was evaluated every 3 months after surgery. The recurrence risk associated with treatment group, cyst volume, and meniscal tear circumference was investigated. RESULTS: This study included 241 young to middle-aged men and women. Of these, 112 underwent arthroscopic excision and 129 underwent arthroscopic decompression. During an average 26-month follow-up period, the arthroscopic decompression group had a sixfold higher recurrence risk [prevalence: 4 and 21 %, respectively; hazard ratio, HR 6.0 (95 % confidence interval, CI 2.3-15.6); p < 0.001] than the arthroscopic excision group. Furthermore, meniscal tears >12 mm in circumference and a cyst volume >2.4 cm(3) conferred a fivefold higher recurrence risk than both lesions of smaller dimensions, both in the overall population and in the arthroscopic decompression group [HRs 5.3 (95 % CI 2.3-12.2) and 5.35 (95 % CI 2.2-13.3), respectively; p values <0.001 for both]. CONCLUSIONS: The suggestion of our study is that the recurrence of parameniscal cysts may be strongly related to large cystic lesions and large meniscal tears. Arthroscopic excision is preferable for treating parameniscal cysts, which are large cystic lesions with large meniscal tears, to reduce the recurrence risk. LEVEL OF EVIDENCE: III. PMID- 26860101 TI - Minimally invasive navigation-assisted versus conventional total knee arthroplasty: a meta-analysis. AB - PURPOSE: It is unclear whether the minimally invasive navigation-assisted (MINA) or conventional (CONv) approach for primary total knee arthroplasty (TKA) leads to better clinical and radiographic outcomes. This meta-analysis compared the clinical and radiographic outcomes of the MINA and CONv approaches after primary TKA. It was hypothesized that there was no difference in clinical and radiographic outcomes between the two surgical approaches for primary TKA. METHODS: This meta-analysis reviewed all studies that compared surgical time, incision length, flexion range of motion (ROM), Knee Society Score ( KSS), coronal mechanical axis (CMA), and coronal femoral component angle (CFCA) with various measurement tools, from direct interview to plain radiography, between the MINA and CONv approaches. RESULTS: Five studies met the inclusion/exclusion criteria for the meta-analysis. The findings of this study suggest that surgical time (95 % CI -18.51 to 39.09; n.s.), KSS (95 % CI -8.55 to 30.84; n.s.), CMA (95 % CI -1.01 to 0.54; n.s.), and CFCA (95 % CI -0.91 to 2.97; n.s.) were similar between the two surgical approaches, whereas incision length (95 % CI -5.18 to 3.69; P < 0.001) was significantly shorter in the MINA approach and flexion ROM (95 % CI 14.26-19.01; P < 0.001) was significantly greater in the MINA approach. CONCLUSIONS: There were no significant differences in clinical and radiographic outcomes, including surgical time, KSS, CMA, and CFCA, in patients who underwent MINA and CONv approach for primary TKA, but the MINA approach resulted in a slightly shorter incision length and increased flexion ROM than the CONv approach. Therefore, if particular attention has to be paid to patient's selection with appropriate counselling and surgeon's experience, MINA approach can provide early clinical benefit when compared with CONv approach. Besides, orthopaedic surgeons need to master the MINA and CONv approaches because both approaches have similar clinical and radiographic outcomes. LEVEL OF EVIDENCE: Therapeutic study, Level II. PMID- 26860102 TI - Magnetic resonance imaging classification of haemodialysis-related amyloidosis of the shoulder: risk factors and arthroscopic treatment. AB - PURPOSE: This study proposed new magnetic resonance imaging (MRI) of haemodialysis shoulders (HDS) focusing on the changes of the rotator cuff, and rotator interval and risk factors for the development of HDS were examined. METHODS: Eighty-five shoulders in 72 patients with a chief complaint of shoulder pain during haemodialysis and at least 10 years of haemodialysis were included. They were classified into 5 groups based on the thickness of the rotator cuff and conditions of rotator interval. Clinical and radiological findings in each grade were examined, and risk factors for the development of HDS were evaluated. Arthroscopic surgeries were performed on 22 shoulders in 20 patients, and arthroscopic findings were also evaluated. RESULTS: Positive correlations for the development of HDS were observed in duration of haemodialysis, positive hepatitis C virus (HCV) infection, and previous haemodialysis-related orthopaedic surgery (P < 0.001, respectively). Strong correlations were observed between positive HCV and the progression of HDS (odds ratio 24.8, 95 % confidence interval 5.7-107.6). Arthroscopically, progression of the surrounding soft tissue degeneration was observed, and operative times were lengthened depending on the progression of MRI grading. CONCLUSION: A new MRI classification of HDS which may be helpful when considering arthroscopic surgeries has been proposed. Positive HCV infection was strongly associated with the progression of HDS on MRI. Conditions of the rotator interval and the rotator cuff based on the MRI classification should be examined when treating HDS patients. LEVEL OF EVIDENCE: III. PMID- 26860103 TI - Anterior cruciate ligament and intercondylar notch growth plateaus prior to cessation of longitudinal growth: an MRI observational study. AB - PURPOSE: Increasing numbers of children and adolescents are being treated for ACL tears. In order for surgeons to safely optimize treatment during ACL surgery, we must better understand ACL growth and intercondylar notch patterns in the skeletally immature knee. The aim of this study is to measure ACL and intercondylar notch volume in paediatric patients and observe how these volumes change as a function of age and gender. METHODS: Data were extracted from the picture archiving and communication systems (PACS) computer records. Sample consisted of 137 MRI knee examinations performed between January 2006 and July 2010 in patients aged 3-13. Subjects were grouped into 1-year age intervals. Patients with imaging reports including ACL tears, previous surgeries, congenital structural anomalies, or syndromes were excluded. RESULTS: Measures of ACL volume significantly increased with age (P < 0.001). A linear increase in ACL volume was observed until the age 10, with a mean increase in volume of 148 mm(3) per age group. ACL volume plateaued at 10 years, after which minimal increase in ACL volume was observed. Sex was not found to be a significant predictor of ACL volume in the multiple linear regression (P = 0.57). Similar to ACL volume, there was a significant increase in intercondylar notch volume with age with a mean increase of 835 mm(3) per age group (P < 0.0001). Intercondylar notch volume reached a plateau at age 10, after which a minimal increase in notch volume was observed in older groups. Female patients had notch volumes that were on average 892 + 259 mm(3) smaller than male patients who were in the same age group (P = 0.0006). CONCLUSION: The plateau in the growth of ACL and notch volume occurs at age 10, prior to the halt in longitudinal growth of boys and girls. Female patients have significantly smaller intercondylar notch volumes than their age matched male counterparts, while no gender difference was seen in ACL volume. These results suggest that notch volume is an intrinsically sex-specific difference, which may contribute to the higher rate of ACL tears among females. These growth patterns are clinically relevant as it allows surgeons to better understand the anatomy, pathology, and risk factors related to ACL tears and its reconstruction. LEVEL OF EVIDENCE: Observational Study, Level IV. PMID- 26860104 TI - Anterior cruciate ligament reconstruction in adolescents (Tanner stages 2 and 3). AB - PURPOSE: Management of anterior cruciate ligament injuries in skeletally immature patients (in Tanner stages 2 and 3) is controversial. Conventional reconstruction used in adults can cause iatrogenic growth disturbance due to physeal damage, and studies that report long-term results using a specific technique are scarce. The aim of this study is to evaluate in a large series the mid- and long-term results of a partial transphyseal technique and define the safe percentage of lesions of the femoral growth plate. METHODS: Between 1989 and 2012, 42 adolescents at risk of growth disturbances (growth prediction of lower limbs >5 cm-Tanner 2, 3) underwent reconstruction of the anterior cruciate ligament using the semitendinosus and gracilis tendons. Growth characteristics of all the patients were assessed preoperatively, and the percentage of damage that would be produced in the femoral physis by the drilling of a 6-mm-diameter tunnel was determined. The technique used achieved graft fixation at both insertion sites, drilling the femoral physis and avoiding the tibial physis. We distinguished two groups: (a) long-term follow-up (mean 13 years 7 months, min 10.9, max 16.2) and (b) medium follow-up (mean 6 years 3 months, min 3.7, max 9.9). All knees were evaluated subjectively by history and objectively by KT2000 testing, and X-rays of both knees were compared for osteoarthritis using the Kellgren-Lawrence classification. RESULTS: In group A (12 patients) one osteoarthritis grade 2, one instability, and ten good stability and function were observed. The mean KT2000 arthrometer values at 30 lb showed a difference of +2.4 mm (range 1-4 mm) between the operated and non-operated sides (p < 0.05). In group B (21 patients) no growth disturbance of the lower limbs, two failures (reinjury while participating in pivoting sports), and 19 good stability and function were observed. The mean KT2000 arthrometer values at 30 lb showed a difference of +1.9 mm (range 1-5 mm) between the operated and non-operated sides (p < 0.05). The average IKDC score of all the patients was 90 (min: 68, max: 97). None of the adolescents had consequences on growth after an eccentric damage passing tendons less than 7% on the frontal plane and of 1% on cross-sectional area of the femoral physis, and after an oblique tunnel passing 6-mm-diameter tendons of the tibial epiphyseal nucleus. CONCLUSIONS: This study defines the possibility to perform a partial transphyseal intra-articular ACL reconstruction in patients in Tanner stages 2 and 3 that avoids tibial physis, involves the distal femoral physis, and produces good results at mid- and long-term follow-up without causing growth disturbances. LEVEL OF EVIDENCE: IV. PMID- 26860105 TI - Survivorship and clinical outcomes of 147 consecutive isolated or combined arthroscopic bone plug free meniscal allograft transplantation. AB - PURPOSE: To present the results of a survival analysis of a series of 147 arthroscopic MAT procedures. METHODS: One-hundred and forty-seven patients (117 males and 30 females) underwent arthroscopic MAT without bone plugs (82 medial MAT and 65 lateral MAT) using fresh-frozen, non-irradiated grafts. They were retrospectively reviewed at a mean of 4.0 +/- 1.9-year follow-up. Mean age at surgery was 40.9 +/- 11.2 (range 16.7-68.8) years; 70 patients (48 %) underwent combined procedures. Clinical evaluation was performed with KOOS, Lysholm and a 0 100 VAS for pain. Survival analysis was performed using two endpoints: surgical failure (revision procedure with direct relation to MAT) and clinical failure (revision procedure or poor Lysholm score, <65). RESULTS: There was a significant (p < 0.05) and clinically relevant decrease in the VAS and increase in KOOS and Lysholm from pre-operative mean score to post-operative mean score. Seven (5 %) patients (two medial and five lateral) experienced surgical failure (five meniscectomies, one lateral graft peripheral suture and one unicompartmental knee arthroplasty). The mean overall survival time was 9.7 years (CI 9.1-10.3). As 16 (11 %) patients presented poor Lysholm score, a total of 23 (16 %) patients were considered clinical failures. The mean overall survival time was 8 years (CI 7.1 8.8). No statistically significant differences in failure and survival rate were present between medial and lateral MAT, isolated or combined MAT, patients >50 or <50 years old and patients with body mass index <25 or >25. CONCLUSIONS: MAT, eventually associated with other needed procedures, was able to significantly relieve pain and improve function of the knee joint at midterm follow-up, with a survival rate from 9.7 to 8.0 years based on failure criteria. Most additional procedures were done in the first 2 post-operative years. MAT eventually associated with other needed procedures could represent an effective treatment for post-meniscectomy syndrome. LEVEL OF EVIDENCE: Therapeutic study, retrospective case series, Level IV. PMID- 26860107 TI - Negotiating excess treatment costs in a clinical research trial: the good, the bad and the innovative. AB - Barriers to recovering the excess treatment costs associated with health research from local organisations in the United Kingdom can increase research costs, delay completion of high- quality studies and risk disenfranchising health trusts and patients from participation. The authors demonstrate how the process for recovering excess treatment costs at a local National Health Service (NHS) trust level in a multicentre study was inconsistent and resulted in excess effort and cost to the research budget. An innovative example of how an organisation acting as a broker between commissioners and researchers facilitated a more timely excess treatment cost agreement is highlighted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN68798818, registered on 18 February 2014. PMID- 26860106 TI - Combination Therapies for Melanoma: A New Standard of Care? AB - Recent data have demonstrated improved survival with targeted and immune therapies in patients with advanced melanoma, leading to much excitement amongst the oncology community and the widespread use of these drugs in combination regimens. However, the place of these combination therapies in the treatment of advanced melanoma remains to be fully determined. In this perspectives article, we critically review the available data and outline the rationale for these combinations being adopted as the standard of care for patients with advanced melanoma in the future. PMID- 26860108 TI - A quick glance at selected topics in this issue. PMID- 26860110 TI - Relation between quantitative coronary CTA and myocardial ischemia by adenosine stress myocardial CT perfusion. AB - BACKGROUND: Coronary-computed tomography angiography (CTA) has limited accuracy to predict myocardial ischemia. Besides luminal area stenosis, other coronary plaque morphology and composition parameters may help to assess ischemia. With the integration of coronary CTA and adenosine stress CT myocardial perfusion (CTP), reliable information regarding coronary anatomy and function can be derived in one procedure. This analysis aimed to investigate the association between coronary stenosis severity, plaque composition and morphology and the presence of ischemia measured with adenosine stress myocardial CTP. METHODS AND RESULTS: 84 patients (age, 62 +/- 10 years; 48% men) who underwent sequential coronary CTA and adenosine stress myocardial CT perfusion were analyzed. Automated quantification was performed in all coronary lesions (quantitative CTA). Downstream myocardial ischemia was assessed by visual analysis of the rest and stress CTP images and defined as a summed difference score of >=1. One or more coronary plaques were present in 146 coronary arteries of which 31 (21%) were ischemia-related. Of the lesions with a stenosis percentage <50%, 50%-70%, and >70%, respectively, 9% (6/67), 18% (9/51), and 57% (16/28) demonstrated downstream ischemia. Furthermore, mean plaque burden, plaque volume, lesion length, maximal plaque thickness, and dense calcium volume were significantly higher in ischemia-related lesions, but only stenosis severity (%) (OR 1.06; 95% CI 1.02-1.10; P = .006) and lesion length (mm) (OR 1.26; 95% CI 1.02-1.55; P = .029) were independent correlates. CONCLUSIONS: Increasing stenosis percentage by quantitative CTA is positively correlated to myocardial ischemia measured with adenosine stress myocardial CTP. However, stenosis percentage remains a moderate determinant. Lumen area stenosis and lesion length were independently associated with ischemia, adjusted for coronary plaque volume, mean plaque burden, maximal lesion thickness, and dense calcium volume. PMID- 26860109 TI - Comparison of phase dyssynchrony analysis using gated myocardial perfusion imaging with four software programs: Based on the Japanese Society of Nuclear Medicine working group normal database. AB - PURPOSE: Left ventricular (LV) phase dyssynchrony parameters based on gated myocardial perfusion imaging varied among software programs. The aim of this study was to determine normal ranges and factors affecting phase parameters. METHODS: Normal databases were derived from the Japanese Society of Nuclear Medicine working group (n = 69). The programs were Emory Cardiac Toolbox with SyncTool (ECTb), Quantitative Gated SPECT (QGS), Heart Function View (HFV), and cardioREPO (cREPO); parameters of phase standard deviation (PSD), 95% bandwidth, and entropy were compared with parameters with ECTb as a reference. RESULTS: PSD (degree) was 5.3 +/- 3.3 for QGS (P < .0001), 5.4 +/- 2.5 for HFV (P < .0001), and 10.3 +/- 3.2 for cREPO (P = n. s.) compared with 11.5 +/- 5.5 for ECTb. Phase bandwidth with three programs differed significantly from ECTb. Gender differences were significant for all programs, indicating larger variation in males. After adjustment of LV volumes between genders, the difference disappeared except for QGS. The phase parameters showed wider variations in patients with the lower ejection fraction (EF) and larger LV volumes, depending on software types. CONCLUSION: Based on normal ranges of phase dyssynchrony parameters in four software programs, dependency on genders, LV volume, and EF should be considered, indicating the need for careful comparison among different software programs. PMID- 26860111 TI - A k-nearest neighbor classification of hERG K(+) channel blockers. AB - A series of 172 molecular structures that block the hERG K(+) channel were used to develop a classification model where, initially, eight types of PaDEL fingerprints were used for k-nearest neighbor model development. A consensus model constructed using Extended-CDK, PubChem and Substructure count fingerprint based models was found to be a robust predictor of hERG activity. This consensus model demonstrated sensitivity and specificity values of 0.78 and 0.61 for the internal dataset compounds and 0.63 and 0.54 for the external (PubChem) dataset compounds, respectively. This model has identified the highest number of true positives (i.e. 140) from the PubChem dataset so far, as compared to other published models, and can potentially serve as a basis for the prediction of hERG active compounds. Validating this model against FDA-withdrawn substances indicated that it may even be useful for differentiating between mechanisms underlying QT prolongation. PMID- 26860112 TI - Extrapolative prediction using physically-based QSAR. AB - Surflex-QMOD integrates chemical structure and activity data to produce physically-realistic models for binding affinity prediction . Here, we apply QMOD to a 3D-QSAR benchmark dataset and show broad applicability to a diverse set of targets. Testing new ligands within the QMOD model employs automated flexible molecular alignment, with the model itself defining the optimal pose for each ligand. QMOD performance was compared to that of four approaches that depended on manual alignments (CoMFA, two variations of CoMSIA, and CMF). QMOD showed comparable performance to the other methods on a challenging, but structurally limited, test set. The QMOD models were also applied to test a large and structurally diverse dataset of ligands from ChEMBL, nearly all of which were synthesized years after those used for model construction. Extrapolation across diverse chemical structures was possible because the method addresses the ligand pose problem and provides structural and geometric means to quantitatively identify ligands within a model's applicability domain. Predictions for such ligands for the four tested targets were highly statistically significant based on rank correlation. Those molecules predicted to be highly active (pK(i) >= 7.5) had a mean experimental pK(i) of 7.5, with potent and structurally novel ligands being identified by QMOD for each target. PMID- 26860113 TI - Occult pneumothorax in blunt trauma: is there a need for tube thoracostomy? AB - INTRODUCTION/BACKGROUND: Occult pneumothorax (OPTX) is defined as air within the pleural cavity that is undetectable on normal chest X-rays, but identifiable on computed tomography. Currently, consensus is divided between tube thoracostomy and conservative management for OPTX. METHODS: The aim of this retrospective study is to determine whether OPTX can be managed conservatively and whether any adverse events occur under conservative management. Data on all trauma patients from 1 Jan 2010 to 31 December 2012 were obtained from our hospital's trauma registry. All patients with occult pneumothorax who had chest X-ray (CXR) and any CT scan visualizing the thorax were included. The exclusion criteria included those with penetrating wounds; CXR showing pneumothorax, hemothorax, or hemopneumothorax; those with prophylactic chest tube insertion before CT; and those with no CT diagnosis of OPTX. The complications of these patients were analyzed to determine if tube thoracostomy is necessary for OPTX and whether not inserting it would alter the outcome significantly. RESULTS: A total of 1564 cases were reviewed and 83 patients were included. Of these 83 patients, 35 (42.2 %) had tube thoracostomy after OPTX detection and 48 (57.8 %) were observed initially. Patients who had tube thoracostomy had similar ISS compared to those without (median ISS 17 vs. 18.5, p = 0.436). Out of the 48 patients who did not have tube thoracostomy on detection of an OPTX, 4 (8.3 %) had complications. In the group of 35 patients who had tube thoracostomy on detection of an OPTX, 7 (20 %) had complications. Of the 83 patients, a total of 12 patients had IPPV, of which 7 (58.3 %) had tube thoracostomy and 5 (41.7 %) did not. Patients who had tube thoracostomy under our care have a statistically significant likelihood of experiencing any complication compared to those without tube thoracostomy (odds ratio 9.92. The median length of stay was also longer (13 days) in those who had tube thoracostomy compared to those without (5 days) (p value = 0.008). CONCLUSIONS: Our study suggests that patients with OPTX can be managed conservatively with close monitoring, but only in areas with ready access to emergency facilities should any adverse events occur. PMID- 26860114 TI - The relationship between widespread changes in gravity and cerebral blood flow. AB - OBJECTIVES: We investigated the dose-effect relationship between wide changes in gravity from 0 to 2.0 Gz (Delta0.5 Gz) and cerebral blood flow (CBF), to test our hypothesis that CBF has a linear relationship with levels of gravity. SUBJECTS AND METHODS: Ten healthy seated men were exposed to 0, 0.5, 1.0, 1.5, and 2.0 Gz for 21 min, by using a tilt chair and a short-arm human centrifuge. Steady-state CBF velocity (CBFV) in the middle cerebral artery by transcranial Doppler ultrasonography, mean arterial pressure (MAP) at the heart level (MAPHeart), heart rate, stroke volume, cardiac output and respiratory conditions were obtained for the last 6 min at each gravity level. Then, MAP in the middle cerebral artery (MAPMCA), reflecting cerebral perfusion pressure, was estimated. RESULTS: Steady-state CBFV decreased stepwise from 0.5 to 2.0 Gz. Steady-state heart rate, stroke volume, estimated MAPMCA and end-tidal carbon dioxide pressure (ETCO2) also changed stepwise from hypogravity to hypergravity. On the other hand, steady-state MAPHeart and cardiac output did not change significantly. Steady-state CBFV positively and linearly correlated with estimated MAPMCA and ETCO2 in most subjects. CONCLUSION: The present study demonstrated stepwise gravity-induced changes in steady-state CBFV from 0.5 to 2.0 Gz despite unchanged steady-state MAPHeart. The combined effects of reduced MAPMCA and ETCO2 likely led to stepwise decreases in CBFV. We caution that a mild increase in gravity from 0 to 2.0 Gz reduces CBF, even if arterial blood pressure at the heart level is maintained. PMID- 26860115 TI - Actinomycosis arising from the nasal cavity, with rare fatal progression. AB - Actinomycosis is a common treatable disease caused by Actinomyces, and generally has a good prognosis. However, we report a fatal case of actinomycosis of the nasal cavity. A 54-year-old man, reporting of left nasal obstruction, swelling and sharp pain around the root of the nose, was referred to our hospital. Histopathological examinations led to a definitive diagnosis of actinomycosis, and oral antibiotics were administered in an outpatient setting. However, the patient discontinued follow-up at the outpatient clinic because of the adverse effects of intravenous delivery, and poor compliance with oral antibiotic therapy led to him receiving a less than adequate dose. Thus, in the absence of sufficient antibiotic treatment, necrosis gradually progressed in the lesion, and the patient died of multiple organ failure and disseminated intravascular coagulation caused by local infection. PMID- 26860117 TI - A novel missense mutation in ATRX uncovered in a Yemeni family leads to alpha thalassemia/mental retardation syndrome without alpha-thalassemia. AB - BACKGROUND: Intellectual disability (ID) features in numerous heritable medical conditions that result from ATRX mutations. Alpha-thalassemia mental retardation syndrome (ATR-X syndrome) is the most notable manifestation of ATRX dysfunction. In addition to ID, genitourinary and craniofacial abnormalities are regularly observed with or without alpha-thalassemia. AIMS: The study sought to characterize two cases of ATR-X in a Yemeni family clinically and molecularly. METHODS: PCR amplification and Sanger sequencing were used to study the ATRX gene in a Yemeni family. Also, methylation-sensitive PCR was used to perform X inactivation studies. CADD, SNAP2 and PolyPhen-2 helped to predict the functional consequences of the variant. RESULTS: Molecular testing revealed a novel hemizygous missense mutation (c.5666T>G) in the ATRX gene in the two Yemeni brothers. This mutation was found in a heterozygous state in the mother, with the chromosome harboring the mutated allele being under strongly skewed X inactivation. CONCLUSIONS: The mutated gene is predicted to have a disrupted SNF 2 domain at a conserved residue; p.Leu1889Trp, which is deemed functionally damaging. This report offers, for the first time, full clinical and molecular characterization of a novel ATRX variant in an Arab family. PMID- 26860116 TI - An exploration of the prevalence and patterns of care for women presenting with mid-trimester loss. AB - BACKGROUND: Mid-trimester loss (MTL) is an area that is poorly defined in the literature and often under reported in clinical practice. The prevalence of MTL in Ireland is uncertain and has a huge impact on the woman, her family and maternity care services. AIMS: To explore the prevalence and patterns of care for women with MTL in a large Maternity hospital in Ireland. METHODS: A descriptive, exploratory study was used involving a retrospective chart audit. RESULTS: 220 women presented with MTL over the 3 year data collection period (January 2011 December 2013), giving a rate of 0.8 % of all deliveries. The majority of women had no previous pregnancy losses and were multiparous (i.e., had a previous pregnancy >500 g). The mean gestational age was 17.69 weeks (SD = 2.73). The mean length of hospital stay was 1.89 days. Intra muscular (IM) analgesia was the most commonly (58.5 %) used medication. Follow up hospital care was received in over 78 % of cases. The majority of women were referred the CMS Bereavement and Chaplain services, with a small number (approx. 5 %) referred to the social worker. Over 46.4 % of families availed of the hospital burial service. CONCLUSIONS: Results suggest the incidence of mid-trimester loss may be slightly lower than the 1 or 2 % of pregnancies reported in the literature. The incidence of mid-trimester loss in multiparous women is approximately twice that of nulliparous women. The referral services offered in the study were utilised by most of the women, as were follow-up clinic appointments. PMID- 26860119 TI - Older patient hospital admissions following primary care referral: the truth is in the referring. AB - BACKGROUND: Health information has a major role in the planning of future healthcare provision. With current reconfiguration and cost saving measures, further demands are being placed on acute hospitals. AIM: To examine the elderly admissions and the referral documentation of older patients admitted to a tertiary level hospital. METHODS: A retrospective analysis of primary care referral documentation for all acute admissions of patients over 75 years to University Hospital Limerick (UHL) over a 2-month period. Documentation was analysed on the basis of patient demographics, presenting complaint and referral source. Primary care referral documentation was then analysed on the basis of presenting complaint, patient demographics, referrer details, and the clinical information provided. RESULTS: Over the 2-month period there were a total of 381 elderly admissions through the Emergency department. The most common presenting complaint was with shortness of breath (21.5 %). 42.5 % of admissions were from a primary care setting. 31.1 % of referrals were typed and 47.0 % handwritten. Over 90 % of referrals contained the patient's name, date of birth and address. 98.7 % of referrals included a presenting complaint and 54 % included a past medical history. 20 % of referrals listed known drug allergies, while 9.3 % documented social history or baseline functional status. Referral letters from general practice and after-hour services were largely similar. CONCLUSIONS: Almost all primary care referrals included the required details as per recent HIQA guidelines. The further inclusion of optional information relating to patient social or functional status, which are of particular relevance to the older population may help patient management. PMID- 26860118 TI - Metformin versus insulin in gestational diabetes mellitus: a meta-analysis of randomized clinical trials. AB - BACKGROUND: Metformin is widely used in treatment of type 2 diabetes. However, whether it is safe for use in pregnancy is controversial. METHODS: A search for relevant studies were performed using PubMed (1948-2014), Embase (1974-2014), the Web of knowledge (1950-2014), and the Cochrane database, included all randomized control trials published in English. RESULTS: Eight RCTs (1712 patients with gestational diabetes mellitus) were retrieved; of those 853 patients were given metformin, and 859 patients were given insulin. Our results showed that metformin does not increase risk of prematurity (RR = 1.26; 95 % CI [0.89, 1.79], P = 0.19). In addition, metformin can either decrease the total weight gain [MD = 1.49, 95 % CI (-2.66, -0.31), P = 0.01] or weight gain after randomization [MD = 1.23, 95 % CI (-1.75, -0.71), P < 0.00001]. No significant differences were observed in patients with pre-eclampsia [RR = 0.82, 95 % CI (0.56, 1.2), P = 0.32] or caesarean section [RR = 0.93, 95 % CI (0.75, 1.16), P = 0.53]. Use of metformin also significantly decreased the risk of neonatal hypoglycemia [RR = 0.58, 95 % CI (0.43, 0.78), P = 0.0003] and admission rates to neonatal intensive care units [RR = 0.74, 95 % CI (0.61, 0.89), P = 0.002]. No other adverse effects were observed, such as hyperbilirubinaemia [RR = 0.83, 95 % CI (0.64, 1.08), P = 0.16], large for gestational age [RR = 0.85, 95 % CI (0.68, 1.05), P = 0.14], small for gestational age [RR = 0.92, 95 % CI (0.61, 1.39), P = 0.69], macrosomia [RR = 0.75, 95 % CI (0.54, 1.03), P = 0.07] or respiratory distress syndrome [RR = 0.88, 95 % CI (0.55, 1.41), P = 0.6]. CONCLUSIONS: Metformin may be beneficial in treating gestational diabetes. However, even more studies are needed to provide more evidence for the future use of metformin. PMID- 26860121 TI - Current exposure to pollution has greater health impact than former exposure, study shows. PMID- 26860120 TI - Exploration and isolation of novel thermophiles in frozen enrichment cultures derived from a terrestrial acidic hot spring. AB - An isolation strategy, exploring novel microorganisms in frozen enrichment cultures (ENFE), which uses a combination of enrichment culture and 16S rRNA gene clone analysis, was evaluated for isolating uncultured thermophiles from a terrestrial acidic hot spring. The procedure comprised (a) multiple enrichment cultures under various conditions, (b) cryostorage of all enrichments, (c) microbial community analyses of the enrichments using 16S rRNA gene sequences, and (d) purification of microorganisms from enrichments containing previously uncultured microorganisms. The enrichments were performed under a total of 36 conditions, and 16 of these enrichments yielded positive microbial growth with the detection of three previously uncultured archaea. Two of the three previously uncultured archaea, strains HS-1 and HS-3, were successfully isolated. Strain HS 1 and HS-3 represented a novel lineage of the order Sulfolobales and novel species of the genus Sulfolobus, respectively. Although innovative isolation methods play strategic roles in isolating previously uncultured microorganisms, the ENFE strategy showed potential for characterizing and isolating such microorganisms using conventional media and techniques. PMID- 26860122 TI - D-penicillamine prevents ram sperm agglutination by reducing the disulphide bonds of a copper-binding sperm protein. AB - Head-to-head agglutination of ram spermatozoa is induced by dilution in the Tyrode's capacitation medium with albumin, lactate and pyruvate (TALP) and ameliorated by the addition of the thiol d-penicillamine (PEN). To better understand the association and disassociation of ram spermatozoa, we investigated the mechanism of action of PEN in perturbing sperm agglutination. PEN acts as a chelator of heavy metals, an antioxidant and a reducing agent. Chelation is not the main mechanism of action, as the broad-spectrum chelator ethylenediaminetetraacetic acid and the copper-specific chelator bathocuproinedisulfonic acid were inferior anti-agglutination agents compared with PEN. Oxidative stress is also an unlikely mechanism of sperm association, as PEN was significantly more effective in ameliorating agglutination than the antioxidants superoxide dismutase, ascorbic acid, alpha-tocopherol and catalase. Only the reducing agents cysteine and DL-dithiothreitol displayed similar levels of non-agglutinated spermatozoa at 0 h compared with PEN but were less effective after 3 h of incubation (37 degrees C). The addition of 10 uM Cu(2+) to 250 uM PEN + TALP caused a rapid reversion of the motile sperm population from a non agglutinated state to an agglutinated state. Other heavy metals (cobalt, iron, manganese and zinc) did not provoke such a strong response. Together, these results indicate that PEN prevents sperm association by the reduction of disulphide bonds on a sperm membrane protein that binds copper. ADAM proteins are possible candidates, as targeted inhibition of the metalloproteinase domain significantly increased the percentage of motile, non-agglutinated spermatozoa (52.0% +/- 7.8) compared with TALP alone (10.6% +/- 6.1). PMID- 26860123 TI - High serum ALP level is associated with increased risk of denosumab-related hypocalcemia in patients with bone metastases from solid tumors. AB - Metastatic bone disease is one of the most common complications of advanced cancers. Pathological fractures, spinal cord compression, and radiotherapy or surgery to the bone are collectively called skeletal-related events (SREs), which cause severe pain, increase hospitalization rates, and impair the quality of life (QOL) of patients with bone metastases. The receptor activator of nuclear factor kB ligand (RANKL)/RANK pathway is critical in the progression of bone metastases. Previous studies have demonstrated that an anti-RANKL antibody (denosumab) was superior to zoledronic acid in prolonging time to first SRE in patients with bone metastases from prostate and breast cancers. However, severe hypocalcemic events occur more frequently after treatment with denosumab compared with zoledronic acid. In this study, 368 administrations of denosumab in 219 patients with metastatic bone disease from solid tumors were analyzed to clarify the risk factors for developing hypocalcemia. The results showed that grade 2/3 hypocalcemia was observed in 10.4% of the total number of denosumab administrations. Patients with higher baseline serum ALP, higher performance status (PS), or gastric cancer were at higher risk for developing hypocalcemia. The cut-off value for ALP to predict denosumab-related hypocalcemia was 587 U/L with a sensitivity of 0.77 and a specificity of 0.81. Close monitoring of serum calcium, especially after the first treatment with denosumab, is strongly recommended in these patients. PMID- 26860124 TI - Vorapaxar monotherapy for secondary stroke prevention: A call for randomized trial. AB - BACKGROUND AND PURPOSE: Vorapaxar, a novel platelet thrombin protease-activated receptor 1 blocker, is currently approved for post-myocardial infarction and peripheral artery disease indications on top of clopidogrel or/and aspirin. We sought to summarize the conflicting stroke data after vorapaxar for justifying a secondary stroke prevention trial. METHODS: Analyses of the stroke data after vorapaxar yielded from thrombin-receptor antagonist vorapaxar in acute coronary syndromes (TRACER) and TRA2P clinical trials, and affiliated Food and Drug Administration (FDA) reviews. RESULTS: The stroke data are mixed, with catastrophic 2.5 excess of intracranial bleeding risks (HR = 2.52; 95% CI = 1.46 4.36, p < 0.0001); trend to worsened second stroke rates (13.0% vs. 11.7%; HR = 1.03; 95% CI = 0.85-1.25, p = NS), but a hint towards less primary ischemic strokes in vorapaxar indicated population (HR = 0.57; 95% CI = 0.43 to 0.75; p < 0.001). These conflicting data are not solely attributed to vorapaxar, but rather reflect unreasonably aggressive triple antiplatelet strategies utilized frequently in TRA2P and dominant in TRACER. Overall, the FDA-confirmed evidence advocates future vorapaxar secondary stroke prevention trial due to being first in-class agent, unique pharmakynetics, and exhibiting very mild "comfort zone" antiplatelet profile. The three arm trial testing head-to-head monotherapy with vorapaxar (Zontivity(r)), versus clopidogrel (Plavix(r)), and versus extended released dipyridamole with very low dose aspirin (Aggrenox(r)) is warranted. CONCLUSIONS: Vorapaxar may be superior to currently recommended antiplatelet strategies and should be tested as a monotherapy in a randomized outcome-driven secondary stroke prevention trial. PMID- 26860125 TI - Tachycardia burden in stroke unit is associated with functional outcome after ischemic stroke. AB - BACKGROUND: Stroke unit care is associated with decrease in mortality and improvement in neurological outcome in patients with acute stroke. Heart rate is a commonly monitored variable in the stroke unit. However, little is known about tachycardia burden in the stroke unit and its association with outcome. AIMS: To investigate the effects of tachycardia burden in the stroke unit on functional outcome in patients with acute ischemic stroke. METHODS: We collected data from 246 patients with acute ischemic stroke admitted to our stroke unit between July 2013 and June 2014. Tachycardia burden was defined as duration of heart rate over 95 per minute divided by the total monitoring time, using the heart rate data sampled every 1 min. We divided the study population into quartiles of tachycardia burden and analyzed their association with poor three-month functional outcome (modified Rankin Scale score of >=3). RESULTS: Among included patients (age, 67.4 +/- 12.8; male, 53.7%), tachycardia burden was 0.7% (median, interquartile range [0.1-5.7%]). The patients with higher tachycardia burdens were older, more likely to have higher stroke severity, cardioembolic etiology, atrial fibrillation, fever, pneumonia, higher initial glucose level, and higher white blood cell count. As compared with the lowest quartile (<0.1%), the highest quartile of tachycardia burden (>=6.0%) was significantly associated with poor outcome (adjusted odds ratio, 5.10; 95% confidence interval, 1.38-18.90; p = 0.01) after adjustment for covariates. CONCLUSIONS: Patients with increased tachycardia burden during stroke unit stay have poor functional outcome. Countermeasures against worsening factors might be utilized for patients with increased tachycardia burden. PMID- 26860126 TI - Prostate Cancer Education in African American Barbershops: Baseline Client Survey Results and Differences in Decisional Conflict and Stage of Decision Making. AB - There have been very few studies to rigorously evaluate the potential of African American barbers to educate men about prostate cancer in the barbershop setting. This research brief presents baseline data from a cross-sectional survey identifying differences in decisional conflict and stage of decision making by screening status from an efficacy trial to educate African American men about informed decision making for prostate cancer screening. Those men who had already received the prostate-specific antigen (PSA) test were more advanced in their stage of decision making and had less decisional conflict about the PSA test than those men who had never received a PSA test. Educational interventions to increase informed decision making with prostate cancer screening must consider previous PSA test history as a mediating variable affecting decision self efficacy. PMID- 26860127 TI - Correlates of Somatic Symptoms Among African American Males Transitioning From a Public System of Care. AB - Exploration of somatic symptoms and their correlates among adolescent and young adult African American males are limited in the empirical literature. In the current study, correlates of somatic symptoms among African American males ( n = 74) transitioning from a public system of care, namely, foster care, was explored. Potential correlates assessed included indicators of child maltreatment, approach and avoidance coping strategies, as well as the following emotional and behavioral problems: oppositional defiant disorder, conduct disorder, major depressive disorder, and attention-deficit hyperactivity disorder. Results indicated that meeting the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, diagnostic criteria for conduct disorder was related to increased somatic symptoms. In addition, greater use of seeking social support as a coping strategy was related to fewer somatic symptoms. The findings provide a good foundation for further exploration of individual, situational, and contextual factors that may influence the physiological and psychological stress responses of vulnerable populations of young African American males. PMID- 26860128 TI - Analysing multiple types of molecular profiles simultaneously: connecting the needles in the haystack. AB - BACKGROUND: It has been shown that a random-effects framework can be used to test the association between a gene's expression level and the number of DNA copies of a set of genes. This gene-set modelling framework was later applied to find associations between mRNA expression and microRNA expression, by defining the gene sets using target prediction information. METHODS AND RESULTS: Here, we extend the model introduced by Menezes et al. 2009 to consider the effect of not just copy number, but also of other molecular profiles such as methylation changes and loss-of-heterozigosity (LOH), on gene expression levels. We will consider again sets of measurements, to improve robustness of results and increase the power to find associations. Our approach can be used genome-wide to find associations and yields a test to help separate true associations from noise. We apply our method to colon and to breast cancer samples, for which genome-wide copy number, methylation and gene expression profiles are available. Our findings include interesting gene expression-regulating mechanisms, which may involve only one of copy number or methylation, or both for the same samples. We even are able to find effects due to different molecular mechanisms in different samples. CONCLUSIONS: Our method can equally well be applied to cases where other types of molecular (high-dimensional) data are collected, such as LOH, SNP genotype and microRNA expression data. Computationally efficient, it represents a flexible and powerful tool to study associations between high-dimensional datasets. The method is freely available via the SIM BioConductor package. PMID- 26860129 TI - Dynamic changes in the gene expression profile during rat oral carcinogenesis induced by 4-nitroquinoline 1-oxide. AB - The typical progression of oral cancer is from hyperplastic epithelial lesions through dysplasia to invasive carcinoma. It is important to investigate malignant oral cancer progression and development in order to determine useful approaches of prevention of dysplastic lesions. The present study aimed to gain insights into the underlying molecular mechanism of oral carcinogenesis by establishing a rat model of oral carcinogenesis using 4-nitroquinoline 1-oxide. Subsequently, transcription profile analysis using an integrating microarray was performed. The dynamic gene expression changes of the six stages of rat oral carcinogenesis (normal, mild epithelial dysplasia, moderate dysplasia, severe dysplasia, carcinoma in situ and oral squamous cell carcinomas) were analyzed using component plane presentations (CPP)-self-organizing map (SOM). Six genes were verified by quantitative polymerase chain reaction, immunohistochemistry and succinate dehydrogenase (SDH) activity assay kit. Numerous differentially expressed genes (DEGs) were identified during rat oral carcinogenesis. CPP-SOM determined that these DEGs were primarily enriched during cell cycle, apoptosis, inflammatory response and tricarboxylic acid cycle, indicating the coordinated regulation of molecular networks. In addition, the expression of specific DEGs, such as janus kinase 3, cyclin-dependent kinase A-1, B-cell chronic lymphocytic leukaemia/lymphoma 2-like 2, nuclear factor-kappaB, tumor necrosis factor receptor superfamily member 1A, cyclin D1 and SDH were identified to have high concordance with the results from microarray data. The current study demonstrated that oral carcinogenesis is a multi-step and multi-gene process, with a distinct pattern alteration along a continuum of malignant transformation. In addition, this comprehensive investigation provided a theoretical basis for the understanding of the molecular alterations associated with oral carcinogenesis. PMID- 26860131 TI - The world changes, but the NHS stays the same. AB - 'In many parts of the NHS, managers are experiencing nursing manpower [sic] difficulties of varying degrees of intensity. These difficulties are characterised by relatively high turnover rates, increasing recruitment difficulties and shortages in some specialties.' PMID- 26860132 TI - Students' bursary protest builds momentum. AB - Nursing students marched on Trafalgar Square to make plain their views on the threat to the NHS bursary. PMID- 26860130 TI - When human immunodeficiency virus (HIV) treatment goals conflict with guideline based opioid prescribing: A qualitative study of HIV treatment providers. AB - BACKGROUND: Human immunodeficiency virus (HIV)-infected patients have a high prevalence of chronic pain and opioid use, making HIV care a critical setting for improving the safety of opioid prescribing. Little is known about HIV treatment providers' perspectives about opioid prescribing to patients with chronic pain. METHODS: The authors administered a questionnaire and conducted semistructured telephone interviews with 18 HIV treatment providers (infectious disease specialists, general internists, family medicine physicians, nurse practitioners, and physician assistants) in Bronx, NY. Open-ended interview questions focused on providers' experiences, beliefs, and attitudes about opioid prescribing and about the use of guideline-based opioid prescribing practices (conservative prescribing, and monitoring for and responding to misuse). Transcripts were thematically analyzed using a modified grounded theory approach. RESULTS: Eighteen HIV treatment providers included 13 physicians, four nurse practitioners, and one physician assistant. They were 62% female, 56% white, and practiced as HIV treatment providers for a mean of 14.6 years. Most reported always or almost always using opioid treatment agreements (56%) and urine drug testing (61%) with their patients on long-term opioid therapy. HIV treatment providers tended to view opioid prescribing for chronic pain within the "HIV paradigm," a set of priorities and principles defined by three key themes: (1) primacy of HIV goals, (2) familiarity with substance use, and (3) the clinician as ally. The HIV paradigm sometimes supported, and sometimes conflicted with, guideline-based opioid prescribing practices. For HIV treatment providers, perceived alignment with the HIV paradigm determined whether and how guideline based opioid prescribing practices were adopted. For example, the primacy of HIV goals superseded conservative opioid prescribing when providers prescribed opioids with the goal of retaining patients in HIV care. CONCLUSION: These findings highlight unique factors in HIV care that influence adoption of guideline-based opioid prescribing practices. These factors should be considered in future research and initiatives to address opioid prescribing in HIV care. PMID- 26860133 TI - Revealed: the price nurses pay for ill-judged postings on social media. AB - Eight nurses have been removed from the register because of inappropriate postings on Facebook and other social media in the past three years. PMID- 26860134 TI - Trusts offered bailout in return for staffing cuts. AB - Hospital chief executives have been told that they need to make significant cuts if they are to receive money from a L1.8 billion bailout planned for April. PMID- 26860135 TI - Carter's cuts should not eclipse focus on safe care, warns RCN. AB - NHS cuts, recommended in Lord Carter's review of productivity, must not be made at the expense of safe care, the RCN has warned. PMID- 26860136 TI - Hospital pays L50 bonuses in bid to plug nursing gap. AB - A hospital has offered its nurses a one-off bonus of L50 to work extra shifts during the winter crisis. PMID- 26860137 TI - Healthcare staff encouraged to warn patients of the risks of the Zika virus. AB - Healthcare workers in primary care should inform pregnant women of the risks associated with the Zika virus if they are travelling to affected countries. PMID- 26860138 TI - Audit report reveals extent of personnel shortfalls. AB - The NHS has a shortfall of 50,000 clinical staff in England, and arrangements for managing staff supply are 'fragmented and do not represent value for money'. PMID- 26860139 TI - Palliative care bill clears two more parliamentary hurdles. AB - A bill aimed at improving patient choice in end of life care has passed two more stages in parliament and moved closer to becoming law. PMID- 26860141 TI - NMC contacts first revalidation group. AB - An 'encouraging' number of nurses have started the Nursing and Midwifery Council's new process for proving they are fit to practise. PMID- 26860142 TI - NHS Scotland staff report rise in assaults at work. AB - Figures show there were 13,957 assaults against NHS staff in Scotland between March and December 2015. PMID- 26860143 TI - New app could help cardiac patients manage condition and avert a crisis. AB - Nurses have hailed a smartphone app that monitors patients' heart conditions and prompts an alert if they are at risk. PMID- 26860144 TI - Let Twitter and Facebook improve rather than ruin your practice. AB - Even though social media is a part of everyday life, many nurses seem wary of using it in their practice. PMID- 26860150 TI - Zika virus. AB - Essential facts Zika virus disease is caused by a virus that is transmitted by the Aedes mosquito. While it generally causes a mild illness, there is increasing concern that it is harmful in pregnancy and can cause congenital abnormalities in infants born to women infected with the virus. There is no antiviral treatment or vaccine currently available. The best form of prevention is protection against mosquito bites. PMID- 26860151 TI - Vanguards: the quest for joined-up care. AB - Organisations in vanguard areas are developing new ways of working to improve and integrate care. In the first article of our three-part series on vanguards, the nurse at NHS England leading the way to new models of care predicts they will become the 'norm for the future'. PMID- 26860152 TI - Better care for men with genital trauma. AB - Mental health nurse Pride Gaka-Chisoro's award-winning research into soldiers' experience of genital trauma led to a pathway that ensures the psychological toll is not overlooked. The pathway includes sperm salvage and psychosexual assessment. Sgt Gaka-Chisoro won a 2015 Nursing Standard Nurse Award. PMID- 26860154 TI - Amazing courage in the Calais 'Jungle'. AB - Staff nurse Holly Howe completed a six-week volunteer placement at the Calais migrant camp's clinic. She found the work heartbreaking, but was amazed by the resilience of the people living in the camp. PMID- 26860155 TI - Time to break the continence taboo. AB - Millions of people in the UK experience continence problems that can have a devastating effect on quality of life. Nurse experts welcome new care guidance from NHS England but say that healthcare staff need to do more to raise patient awareness of available treatment options. PMID- 26860168 TI - Meds are no panacea for children who might have ADHD. AB - I agree caution needs to be exercised in using methylphenidate, most commonly known as Ritalin, for attention deficit hyperactivity disorder in children, (clinical update, January 20). PMID- 26860169 TI - With every route into nursing comes criticism of graduates. AB - With the announcement of the new 'apprentice' route into nursing, those at university should cover their ears because there is bound to be a barrage of criticism aimed at nurses with degrees. PMID- 26860170 TI - In-house nursing pools are better for patients--and the bottom line. AB - In an interview with the Telegraph, heath secretary Jeremy Hunt said it was unacceptable for agencies to make big profits from the NHS and promised action on the matter. PMID- 26860171 TI - Most nurses I know don't have time to spend money in the pub. AB - I am not sure including a pint of lager in your comparisons to illustrate the inflationary pressures nurses endure while they face yet more pay restraint is justified (news analysis, January 27). PMID- 26860172 TI - Be vigilant, this government is coming after your pay. AB - When chancellor George Osborne accepted what might have been a couple of luncheon vouchers from Google in payment of ten years' unpaid UK tax, the Department of Health submitted its evidence to the Pay Review Body in favour of extending 'plain time working' and introducing performance-related incremental pay progression. PMID- 26860175 TI - How to perform an episiotomy. AB - RATIONALE AND KEY POINTS: An episiotomy may be necessary to assist some women to give birth. An episiotomy is a surgical incision intentionally made to increase the diameter of the vulval outlet to enable childbirth. ? Midwives and doctors should use their clinical judgement and skills to assess when to perform an episiotomy. ? An episiotomy should not be performed routinely; its use should be restricted to certain indications. ? Adequate pain relief should be provided before performing an episiotomy. REFLECTIVE ACTIVITY: Clinical skills articles can help update your practice and ensure it remains evidence based. Apply this article to your practice. Reflect on and write a short account of: 1. How you think this article will change your practice. 2. The risk factors that can predispose a woman to having an episiotomy. 3. What you would do if a woman refused to have an episiotomy despite the presence of a clinical indication, such as fetal distress. Subscribers can upload their reflective accounts at: rcni.com/portfolio. PMID- 26860176 TI - Nursing theory and the delivery of compassionate care. AB - Compassionate care is a priority in current healthcare policy. However, its definition is amorphous, leading to difficulties standardising it in practice. This article discusses how nursing theory is central to the delivery of compassionate care. It emphasises the need to develop a theoretical framework that reflects the eclectic and pragmatic nature of nursing practice, and the importance of using patient feedback as an indicator of the quality of care and as a basis for adapting theoretical hypotheses. PMID- 26860177 TI - Discharging patients from acute care hospitals. AB - Planning for patient discharge is an essential element of any admission to an acute setting, but may often be left until the patient is almost ready to leave hospital. This article emphasises why discharge planning is important and lists the essential principles that should be addressed to ensure that patients leave at an optimum time, feeling confident and safe to do so. Early assessment, early planning and co-ordination of all the teams involved in the patient's care are essential. Effective communication between the various teams and with the patient and their family or carer(s) is necessary. Patients should leave hospital with all the information, medications and equipment they require. Appropriate plans should have been developed and communicated to the receiving community or non acute team. When patient discharge is effective, complications as a result of extended lengths of hospital stay are prevented, hospital beds are used efficiently and readmissions are reduced. PMID- 26860178 TI - Mentoring and the 6Cs. AB - As a staff nurse in a rehabilitation unit, I have been involved in patient care initiatives using the 6Cs of nursing: care, compassion, competence, communication, courage and commitment. However, I had not appreciated the benefits of using the 6Cs of nursing in the mentorship role. PMID- 26860179 TI - Clear communication. AB - In health care, effective communication can directly affect positive outcomes. Ineffective or poor communication can cost lives, be it by a missed diagnosis, a medication error or treatment delay. PMID- 26860180 TI - A vital part of the surgical team. AB - The traditional surgical workforce has changed--and it continues to do so. PMID- 26860183 TI - Student life--'Death is part of the job'. AB - Caring for patients who have died and their relatives can be humbling, stressful and emotional for even the most experienced nurse. PMID- 26860185 TI - Demographic and clinical features of ALS in northeastern Iran from March 2007 through March 2013; A case series study. PMID- 26860184 TI - Nanotubes-Embedded Indocyanine Green-Hyaluronic Acid Nanoparticles for Photoacoustic-Imaging-Guided Phototherapy. AB - Phototherapy is a light-triggered treatment for tumor ablation and growth inhibition via photodynamic therapy (PDT) and photothermal therapy (PTT). Despite extensive studies in this area, a major challenge is the lack of selective and effective phototherapy agents that can specifically accumulate in tumors to reach a therapeutic concentration. Although recent attempts have produced photosensitizers complexed with photothermal nanomaterials, the tedious preparation steps and poor tumor efficiency of therapy still hampers the broad utilization of these nanocarriers. Herein, we developed a CD44 targeted photoacoustic (PA) nanophototherapy agent by conjugating Indocyanine Green (ICG) to hyaluronic acid nanoparticles (HANPs) encapsulated with single-walled carbon nanotubes (SWCNTs), resulting in a theranostic nanocomplex of ICG-HANP/SWCNTs (IHANPT). We fully characterized its physical features as well as PA imaging and photothermal and photodynamic therapy properties in vitro and in vivo. Systemic delivery of IHANPT theranostic nanoparticles led to the accumulation of the targeted nanoparticles in tumors in a human cancer xenograft model in nude mice. PA imaging confirmed targeted delivery of the IHANPT nanoparticles into tumors (T/M ratio = 5.19 +/- 0.3). The effect of phototherapy was demonstrated by low power laser irradiation (808 nm, 0.8 W/cm(2)) to induce efficient photodynamic effect from ICG dye. The photothermal effect from the ICG and SWCNTs rapidly raised the tumor temperature to 55.4 +/- 1.8 degrees C. As the result, significant tumor growth inhibition and marked induction of tumor cell death and necrosis were observed in the tumors in the tumors. There were no apparent systemic and local toxic effects found in the mice. The dynamic thermal stability of IHANPT was studied to ensure that PTT does not affect ICG-dependent PDT in phototherapy. Therefore, our results highlight imaging property and therapeutic effect of the novel IHANPT theranostic nanoparticle for CD44 targeted and PA image-guided dual PTT and PDT cancer therapy. PMID- 26860186 TI - Interleukin-2: a double-edge sword in allogeneic stem cell transplantation. PMID- 26860187 TI - Anthracycline or trastuzumab-related cardiotoxicity: do we have a predictive biomarker? AB - Chemotherapy-induced cardiotoxicity, is a well-known and potentially serious complication strongly impacting the quality of life and overall survival of breast cancer patients. The current diagnostic approach to detect cardiac damage is the estimation of left ventricular ejection fraction by echocardiography. However, this approach exhibits less sensitivity toward early prediction of cardiomyopathy, not allowing for preventive strategies. Measurement of serum cardiac-specific biomarkers can be a valid diagnostic tool for identifying patients prone to developing cardiotoxocity and in whom closer cardiac monitoring and preventive strategies are pivotal. In this article, we review work done on biomarkers in recent years, with an emphasis on troponin and B-type natriuretic peptide, which are currently the most studied in this field. We also briefly discuss current and emerging imaging techniques for early detection of cardiomyopathy. PMID- 26860189 TI - Measurement properties of quality of life measurement instruments for infants, children and adolescents with eczema: protocol for a systematic review. AB - BACKGROUND: Eczema is a common chronic or chronically relapsing, inflammatory skin disease that exerts a substantial negative impact on quality of life (QoL). The Harmonising Outcome Measures for Eczema (HOME) initiative has used a consensus-based process which identified QoL as one of the four core outcome domains to be assessed in all eczema clinical trials. A number of measurement instruments exist to measure QoL in infants, children, and adolescents with eczema, and there is a great variability in both content and quality of the instruments used. Therefore, the objective of the proposed research is to comprehensively and systematically assess the measurement properties of the existing measurement instruments that were developed and/or validated for the measurement of patient-reported QoL in infants, children, and adolescents with eczema. METHODS/DESIGN: This study is a systematic review of the measurement properties of patient-reported measures of QoL developed and/or validated for infants, children, and adolescents with eczema. A systematic literature search will be carried out in MEDLINE via PubMed and EMBASE using a selection of relevant search terms. Eligible studies will be primary empirical studies evaluating, describing, or comparing measurement properties of QoL instruments for infants, children, and adolescents with eczema. Two reviewers will independently perform eligibility assessment and data abstraction. Evidence tables will be used to record study characteristics, instrument characteristics, measurement properties, and interpretability. The adequacy of the measurement properties will be assessed using predefined criteria. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist will be used to evaluate the methodological quality of included studies. A best evidence synthesis will be undertaken if more than one study has examined a particular measurement property. DISCUSSION: The proposed systematic review will yield a comprehensive assessment of measurement properties of existing QoL instruments in infants, children, and adolescents with eczema. The results will serve as a basis to recommend a QoL measurement instrument for infants, one for children, and one for adolescents for use in future clinical trials. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015023483. PMID- 26860188 TI - Cocaine-mediated induction of microglial activation involves the ER stress-TLR2 axis. AB - BACKGROUND: Neuroinflammation associated with advanced human immunodeficiency virus (HIV)-1 infection is often exacerbated by chronic cocaine abuse. Cocaine exposure has been demonstrated to mediate up-regulation of inflammatory mediators in in vitro cultures of microglia. The molecular mechanisms involved in this process, however, remain poorly understood. In this study, we sought to explore the underlying signaling pathways involved in cocaine-mediated activation of microglial cells. METHODS: BV2 microglial cells were exposed to cocaine and assessed for toll-like receptor (TLR2) expression by quantitative polymerase chain reaction (qPCR), western blot, flow cytometry, and immunofluorescence staining. The mRNA and protein levels of cytokines (TNFalpha, IL-6, MCP-1) were detected by qPCR and ELISA, respectively; level of reactive oxygen species (ROS) production was examined by the Image-iT LIVE Green ROS detection kit; activation of endoplasmic reticulum (ER)-stress pathways were detected by western blot. Chromatin immunoprecipitation (ChIP) assay was employed to discern the binding of activating transcription factor 4 (ATF4) with the TLR2 promoter. Immunoprecipitation followed by western blotting with tyrosine antibody was used to determine phosphorylation of TLR2. Cocaine-mediated up-regulation of TLR2 expression and microglial activation was validated in cocaine-injected mice. RESULTS: Exposure of microglial cells to cocaine resulted in increased expression of TLR2 with a concomitant induction of microglial activation. Furthermore, this effect was mediated by NADPH oxidase-mediated rapid accumulation of ROS with downstream activation of the ER-stress pathways as evidenced by the fact that cocaine exposure led to up-regulation of pPERK/peIF2alpha/ATF4 and TLR2. The novel role of ATF4 in the regulation of TLR2 expression was confirmed using genetic and pharmacological approaches. CONCLUSIONS: xThe current study demonstrates that cocaine-mediated activation of microglia involves up-regulation of TLR2 through the ROS-ER stress-ATF4-TLR2 axis. Understanding the mechanism(s) involved in cocaine-mediated up-regulation of ROS-ER stress/TLR2 expression and microglial activation could have implications for the development of potential therapeutic targets aimed at resolving neuroinflammation in cocaine abusers. PMID- 26860190 TI - What is normal? Next generation sequencing-driven analysis of the human circulating miRNAOme. AB - BACKGROUND: MicroRNAs (miRNAs) are short non-protein-coding RNA species that have a regulatory function in modulating protein translation and degradation of specific mRNAs. MicroRNAs are estimated to target approximately 60% of all human mRNAs and are associated with the regulation of all physiological processes. Similar to many messenger RNAs (mRNA), miRNAs exhibit marked tissue specificity, and appear to be dysregulated in response to specific pathological conditions. Perhaps, one of the most significant findings is that miRNAs are detectable in various biological fluids and are stable during routine clinical processing, paving the way for their use as novel biomarkers. Despite an increasing number of publications reporting individual miRNAs or miRNA signatures to be diagnostic of disease or indicative of response to therapy, there is still a paucity of baseline data necessary for their validation. To this end, we utilised state of the art sequencing technologies to determine the global expression of all circulating miRNAs within the plasma of 18 disease-free human subjects. RESULTS: In excess of 500 miRNAs were detected in our study population with expression levels across several orders of magnitude. Ten highly expressed miRNAs accounted for 90% of the total reads that mapped showing that despite the range of miRNAs present, the total miRNA load of the plasma was predominated by just these few species (50% of which are blood cell associated). Ranges of expression were determined for all miRNA detected (>500) and a set of highly stable miRNAs identified. Finally, the effects of gender, smoking status and body mass index on miRNA expression were determined. CONCLUSIONS: The data contained within will be of particular use to researchers performing miRNA-based biomarker screening in plasma and allow shortlisting of candidates a priori to expedite discovery or reduce costs as required. PMID- 26860191 TI - Multiscale Poincare plots for visualizing the structure of heartbeat time series. AB - BACKGROUND: Poincare delay maps are widely used in the analysis of cardiac interbeat interval (RR) dynamics. To facilitate visualization of the structure of these time series, we introduce multiscale Poincare (MSP) plots. METHODS: Starting with the original RR time series, the method employs a coarse-graining procedure to create a family of time series, each of which represents the system's dynamics in a different time scale. Next, the Poincare plots are constructed for the original and the coarse-grained time series. Finally, as an optional adjunct, color can be added to each point to represent its normalized frequency. RESULTS: We illustrate the MSP method on simulated Gaussian white and 1/f noise time series. The MSP plots of 1/f noise time series reveal relative conservation of the phase space area over multiple time scales, while those of white noise show a marked reduction in area. We also show how MSP plots can be used to illustrate the loss of complexity when heartbeat time series from healthy subjects are compared with those from patients with chronic (congestive) heart failure syndrome or with atrial fibrillation. CONCLUSIONS: This generalized multiscale approach to Poincare plots may be useful in visualizing other types of time series. PMID- 26860192 TI - Strengthening national capacities for researching on Social Determinants of Health (SDH) towards informing and addressing health inequities in Tanzania. AB - BACKGROUND: Tanzania's socio-economic development is challenged by sharp inequities between and within urban and rural areas, and among different socio economic groups. This paper discusses the importance of strengthening SDH research, knowledge, relevant capacities and responsive systems towards addressing health inequities in Tanzania. METHODS: Based on a conceptual framework for building SDH research capacity, a mapping of existing research systems was undertaken between February and June 2012. It involved a review of national policies, strategies and published SDH-related research outputs from 2005 onwards, and 34 in-depth interviews with a range of stakeholders in Tanzania. RESULTS: The conceptualization of SDH varies considerably among stakeholders and their professional background, but with some consensus that it is linked to "inequities" being a consequence of poverty, poor planning, limited attention to basic humanity and citizenship rights, weak governance structures and inefficient use of available resources. Commonly perceived SDH factors include age, income, education, beliefs, cultural norms, gender, occupation, nutritional status, access to health care, access to safe water and sanitation and child bearing practices. SDH research is in its infancy but gaining momentum. In the absence of a specific "SDH portfolio", SDH research is scattered and hidden within disease specific, poverty-related research and research on universal health coverage. Research is mainly externally funded, which has implications on the focus of context specific SDH research, national priorities and transfer to policy. This create mismatch with population and research capacity needs. CONCLUSION: Most research analysis in the country fails to consider the context specific structural determinants of health and inequities towards a broader understanding of existing vulnerabilities. The challenge is on promoting a culture of critical inter-disciplinary research and analysis that is central to SDH research. Establishing a system to promote collaboration across sectors and strengthen collective capacities for individuals and institutions researching in SDH will augment existing SDH research initiatives and better inform appropriate intersectoral policies towards addressing prevailing health inequities across the country. PMID- 26860193 TI - Prediction of anticancer molecules using hybrid model developed on molecules screened against NCI-60 cancer cell lines. AB - BACKGROUND: In past, numerous quantitative structure-activity relationship (QSAR) based models have been developed for predicting anticancer activity for a specific class of molecules against different cancer drug targets. In contrast, limited attempt have been made to predict the anticancer activity of a diverse class of chemicals against a wide variety of cancer cell lines. In this study, we described a hybrid method developed on thousands of anticancer and non-anticancer molecules tested against National Cancer Institute (NCI) 60 cancer cell lines. RESULTS: Our analysis of anticancer molecules revealed that majority of anticancer molecules contains 18-24 carbon atoms and are dominated by functional groups like R2NH, R3N, ROH, RCOR, and ROR. It was also observed that certain substructures (e.g., 1-methoxy-4-methylbenzene, 1-methoxy benzene, Nitrobenzene, Indole, Propenyl benzene) are more abundant in anticancer molecules. Next, we developed anticancer molecule prediction models using various machine-learning techniques and achieved maximum matthews correlation coefficient (MCC) of 0.81 with 90.40% accuracy using support vector machine (SVM) based models. In another approach, a novel similarity or potency score based method has been developed using selected fragments/fingerprints and achieved maximum MCC of 0.82 with 90.65% accuracy. Finally, we combined the strength of above methods and developed a hybrid method with maximum MCC of 0.85 with 92.47% accuracy. CONCLUSIONS: We developed a hybrid method utilizing the best of machine learning and potency score based method. The highly accurate hybrid method can be used for classification of anticancer and non-anticancer molecules. In order to facilitate scientific community working in the field of anticancer drug discovery, we integrate hybrid and potency method in a web server CancerIN. This server provides various facilities that includes; virtual screening of anticancer molecules, analog based drug design, and similarity with known anticancer molecules ( http://crdd.osdd.net/oscadd/cancerin). PMID- 26860195 TI - Purcell effect and Lamb shift as interference phenomena. AB - The Purcell effect and Lamb shift are two well-known physical phenomena which are usually discussed in the context of quantum electrodynamics, with the zero-point vibrations as a driving force of those effects in the quantum approach. Here we discuss the classical counterparts of these quantum effects in photonics, and explain their physics trough interference wave phenomena. As an example, we consider a waveguide in a planar photonic crystal with a side-coupled defect, and demonstrate a perfect agreement between the results obtained on the basis of quantum and classic approaches and reveal their link to the Fano resonance. We find that in such a waveguide-cavity geometry the Purcell effect can modify the lifetime by at least 25 times, and the Lamb shift can exceed 3 half-widths of the cavity spectral line. PMID- 26860194 TI - Gastric microbiota and predicted gene functions are altered after subtotal gastrectomy in patients with gastric cancer. AB - Subtotal gastrectomy (i.e., partial removal of the stomach), a surgical treatment for early-stage distal gastric cancer, is usually accompanied by highly selective vagotomy and Billroth II reconstruction, leading to dramatic changes in the gastric environment. Based on accumulating evidence of a strong link between human gut microbiota and host health, a 2-year follow-up study was conducted to characterize the effects of subtotal gastrectomy. Gastric microbiota and predicted gene functions inferred from 16S rRNA gene sequencing were analyzed before and after surgery. The results demonstrated that gastric microbiota is significantly more diverse after surgery. Ralstonia and Helicobacter were the top two genera of discriminant abundance in the cancerous stomach before surgery, while Streptococcus and Prevotella were the two most abundant genera after tumor excision. Furthermore, N-nitrosation genes were prevalent before surgery, whereas bile salt hydrolase, NO and N2O reductase were prevalent afterward. To our knowledge, this is the first report to document changes in gastric microbiota before and after surgical treatment of stomach cancer. PMID- 26860197 TI - Probing the spectral density of the surface electromagnetic fields through scattering of waveguide photons. AB - The spectral density of the metal-surface electromagnetic fields will be strongly modified in the presence of a closely-spaced quantum emitter. In this work, we propose a feasible way to probe the changes of the spectral density through the scattering of the waveguide photon incident on the quantum emitter. The variances of the lineshape in the transmission spectra indicate the coherent interaction between the emitter and the pseudomode resulting from all the surface electromagnetic modes. We further investigate the quantum coherence between the emitter and the pseudomode of the metal-dielectric interface. PMID- 26860196 TI - Defining Core and Penumbra in Ischemic Stroke: A Voxel- and Volume-Based Analysis of Whole Brain CT Perfusion. AB - Whole brain computed tomography perfusion (CTP) has the potential to select eligible patients for reperfusion therapy. We aimed to find the optimal thresholds on baseline CTP for ischemic core and penumbra in acute ischemic stroke. We reviewed patients with acute ischemic stroke in the anterior circulation, who underwent baseline whole brain CTP, followed by intravenous thrombolysis and perfusion imaging at 24 hours. Patients were divided into those with major reperfusion (to define the ischemic core) and minimal reperfusion (to define the extent of penumbra). Receiver operating characteristic (ROC) analysis and volumetric consistency analysis were performed separately to determine the optimal threshold by Youden's Index and mean magnitude of volume difference, respectively. From a series of 103 patients, 22 patients with minimal-reperfusion and 47 with major reperfusion were included. Analysis revealed delay time >= 3 s most accurately defined penumbra (AUC = 0.813; 95% CI, 0.812-0.814, mean magnitude of volume difference = 29.1 ml). The optimal threshold for ischemic core was rCBF <= 30% within delay time >= 3 s (AUC = 0.758; 95% CI, 0.757-0.760, mean magnitude of volume difference = 10.8 ml). In conclusion, delay time >= 3 s and rCBF <= 30% within delay time >= 3 s are the optimal thresholds for penumbra and core, respectively. These results may allow the application of the mismatch on CTP to reperfusion therapy. PMID- 26860198 TI - Origins of cattle on Chirikof Island, Alaska, elucidated from genome-wide SNP genotypes. AB - Feral livestock may harbor genetic variation of commercial, scientific, historical or esthetic value. The origins and uniqueness of feral cattle on Chirikof Island, Alaska, are uncertain. The island is now part of the Alaska Maritime Wildlife Refuge and Federal wildlife managers want grazing to cease, presumably leading to demise of the cattle. Here we characterize the cattle of Chirikof Island relative to extant breeds and discern their origins. Our analyses support the inference that Yakut cattle from Russia arrived first on Chirikof Island, then ~120 years ago the first European taurine cattle were introduced to the island, and finally a large wave of Hereford cattle were introduced on average 40 years ago. In addition, this mixture of European and East-Asian cattle is unique compared with other North American breeds and we find evidence that natural selection in the relatively harsh environment of Chirikof Island has further impacted their genetic architecture. These results provide an objective basis for decisions regarding conservation of the Chirikof Island cattle. PMID- 26860200 TI - Genome-wide prediction models that incorporate de novo GWAS are a powerful new tool for tropical rice improvement. AB - To address the multiple challenges to food security posed by global climate change, population growth and rising incomes, plant breeders are developing new crop varieties that can enhance both agricultural productivity and environmental sustainability. Current breeding practices, however, are unable to keep pace with demand. Genomic selection (GS) is a new technique that helps accelerate the rate of genetic gain in breeding by using whole-genome data to predict the breeding value of offspring. Here, we describe a new GS model that combines RR-BLUP with markers fit as fixed effects selected from the results of a genome-wide association study (GWAS) on the RR-BLUP training data. We term this model GS + de novo GWAS. In a breeding population of tropical rice, GS + de novo GWAS outperformed six other models for a variety of traits and in multiple environments. On the basis of these results, we propose an extended, two-part breeding design that can be used to efficiently integrate novel variation into elite breeding populations, thus expanding genetic diversity and enhancing the potential for sustainable productivity gains. PMID- 26860201 TI - It's a bear market: evolutionary and ecological effects of predation on two wild sockeye salmon populations. AB - Predation can affect both phenotypic variation and population productivity in the wild, but quantifying evolutionary and demographic effects of predation in natural environments is challenging. The aim of this study was to estimate selection differentials and coefficients associated with brown bear (Ursus arctos) predation in wild sockeye salmon (Oncorhynchus nerka) populations spawning in pristine habitat that is often subject to intense predation pressure. Using reconstructed genetic pedigrees, individual reproductive success (RS) was estimated in two sockeye salmon populations for two consecutive brood years with very different predation intensities across brood years. Phenotypic data on individual adult body length, body depth, stream entry timing and reproductive lifespan were used to calculate selection coefficients based on RS, and genetic variance components were estimated using animal models. Bears consistently killed larger and more recently arrived adults, although selection differentials were small. In both populations, mean RS was higher in the brood year experiencing lower predation intensity. Selection coefficients were similar across brood years with different levels of predation, often indicating stabilizing selection on reproductive lifespan as well as directional selection for longer reproductive lifespan. Despite these selection pressures, genetic covariation of morphology, phenology and lifespan appears to have maintained variation in spawner body size and stream entry timing in both populations. Our results therefore suggest considerable demographic but limited evolutionary effects of bear predation in the two study populations. PMID- 26860199 TI - Contrasting evolutionary histories of MHC class I and class II loci in grouse- effects of selection and gene conversion. AB - Genes of the major histocompatibility complex (MHC) encode receptor molecules that are responsible for recognition of intracellular and extracellular pathogens (class I and class II genes, respectively) in vertebrates. Given the different roles of class I and II MHC genes, one might expect the strength of selection to differ between these two classes. Different selective pressures may also promote different rates of gene conversion at each class. Despite these predictions, surprisingly few studies have looked at differences between class I and II genes in terms of both selection and gene conversion. Here, we investigated the molecular evolution of MHC class I and II genes in five closely related species of prairie grouse (Centrocercus and Tympanuchus) that possess one class I and two class II loci. We found striking differences in the strength of balancing selection acting on MHC class I versus class II genes. More than half of the putative antigen-binding sites (ABS) of class II were under positive or episodic diversifying selection, compared with only 10% at class I. We also found that gene conversion had a stronger role in shaping the evolution of MHC class II than class I. Overall, the combination of strong positive (balancing) selection and frequent gene conversion has maintained higher diversity of MHC class II than class I in prairie grouse. This is one of the first studies clearly demonstrating that macroevolutionary mechanisms can act differently on genes involved in the immune response against intracellular and extracellular pathogens. PMID- 26860202 TI - Dopaminergic Neurotransmission in the Nucleus Accumbens Modulates Social Play Behavior in Rats. AB - Social play behavior is a highly rewarding form of social interaction displayed by young mammals. Social play is important for neurobehavioral development and it has been found to be impaired in several developmental psychiatric disorders. In line with the rewarding properties of social play, we have previously identified the nucleus accumbens (NAc) as an important site of action for endocannabinoid and opioid modulation of this behavior. NAc dopamine has a well-known role in certain components of reward processes, such as incentive motivation. However, its contribution to the positive emotional aspects of social interactions is less clear. Therefore, we investigated the role of dopaminergic neurotransmission in the NAc in social play behavior in rats. We found that intra-NAc infusion of the dopamine releaser/reuptake inhibitor amphetamine increased social play behavior that was dependent on activation of both D1 and D2 dopamine receptors. This increase in social play behavior was mimicked by intra-NAc infusion of the dopamine receptor agonist apomorphine, but not of the dopamine reuptake inhibitor GBR-12909. Blockade of either D1 or D2 NAc dopamine receptors reduced social play in animals highly motivated to play as a result of longer social isolation before testing. Last, blockade of NAc dopamine receptors prevented the play-enhancing effects of endocannabinoid and opioid receptor stimulation. These findings demonstrate an important modulatory role of NAc dopaminergic neurotransmission in social play. Thus, functional activity in the mesolimbic dopamine pathway plays an important role in adaptive social development, whereas abnormal NAc dopamine function may underlie the social impairments observed in developmental psychiatric disorders such as autism, attention deficit hyperactivity disorder or early-onset schizophrenia. PMID- 26860203 TI - Early-Life Social Isolation Stress Increases Kappa Opioid Receptor Responsiveness and Downregulates the Dopamine System. AB - Chronic early-life stress increases vulnerability to alcoholism and anxiety disorders during adulthood. Similarly, rats reared in social isolation (SI) during adolescence exhibit augmented ethanol intake and anxiety-like behaviors compared with group housed (GH) rats. Prior studies suggest that disruption of dopamine (DA) signaling contributes to SI-associated behaviors, although the mechanisms underlying these alterations are not fully understood. Kappa opioid receptors (KORs) have an important role in regulating mesolimbic DA signaling, and other kinds of stressors have been shown to augment KOR function. Therefore, we tested the hypothesis that SI-induced increases in KOR function contribute to the dysregulation of NAc DA and the escalation in ethanol intake associated with SI. Our ex vivo voltammetry experiments showed that the inhibitory effects of the kappa agonist U50,488 on DA release were significantly enhanced in the NAc core and shell of SI rats. Dynorphin levels in NAc tissue were observed to be lower in SI rats. Microdialysis in freely moving rats revealed that SI was also associated with reduced baseline DA levels, and pretreatment with the KOR antagonist nor binaltorphimine (nor-BNI) increased DA levels selectively in SI subjects. Acute ethanol elevated DA in SI and GH rats and nor-BNI pretreatment augmented this effect in SI subjects, while having no effect on ethanol-stimulated DA release in GH rats. Together, these data suggest that KORs may have increased responsiveness following SI, which could lead to hypodopaminergia and contribute to an increased drive to consume ethanol. Indeed, SI rats exhibited greater ethanol intake and preference and KOR blockade selectively attenuated ethanol intake in SI rats. Collectively, the findings that nor-BNI reversed SI-mediated hypodopaminergic state and escalated ethanol intake suggest that KOR antagonists may represent a promising therapeutic strategy for the treatment of alcohol use disorders, particularly in cases linked to chronic early-life stress. PMID- 26860204 TI - Ankyrin Repeat Domain 1 is Up-regulated During Hepatitis C Virus Infection and Regulates Hepatitis C Virus Entry. AB - Hepatitis C virus (HCV) is highly dependent on host proteins for its own propagation. By transcriptome sequencing (RNA-Seq) analysis, we identified 30 host genes that were significantly differentially expressed in cell culture-grown HCV (HCVcc)-infected cells. Of these candidate genes, we selected and characterized ankyrin repeat domain 1 (ANKRD1). Here, we showed that protein expression of ANKRD1 was up-regulated in HCVcc-infected cells. We further showed that protein expression level of ANKRD1 was increased by nonstructural 5A (NS5A) protein. ANKRD1 specifically interacted with NS5A both in vitro and coimmunoprecipitation assays. Protein interaction was mediated through the domain II of NS5A and the C-terminal region of ANKRD1. Promoter activity of ANKRD1 was also increased by NS5A protein. Moreover, up-regulation of ANKRD1 expression was mediated through alteration in intracellular calcium homeostasis and ER stress in HCVcc-infected cells. We showed that silencing of ANKRD1 impaired HCV propagation without affecting HCV replication. By using HCV-like infectious particle (HCV LP), we demonstrated that HCV single-cycle infection was drastically impaired in ANKRD1 knockdown cells. Finally, we verified that ANKRD1 was required for HCV entry. These data suggest that HCV coopts ANKRD1 for its own propagation and up regulation of ANKRD1 may contribute to HCV-mediated liver pathogenesis. PMID- 26860205 TI - A case report of successful treatment of 90 degrees knee flexion contracture in a patient with adult-onset Still's disease. AB - BACKGROUND: Severe knee flexion contractures greater than 80 degrees are rare and challenging to manage. Previous studies have demonstrated unsatisfactory clinical results after correcting these deformities because residual flexion contractures were not corrected within a short period of time. We herein report the case of a patient with adult-onset Still's disease with 90 degrees of bilateral knee flexion contracture, which was successfully corrected by total knee arthroplasty and serial casting over a period of five weeks. CASE PRESENTATION: A 47-year-old male was admitted to our orthopedic department for bilateral knee pain and a preoperative fixed flexion contracture of 90 degrees . A diagnosis of adult-onset Still's disease was made based on the patient's medical history of a high spiking fever, salmon-colored rash and bilateral knee and wrist pain. Bilateral total knee arthroplasty was carried out to address these deformities, but residual flexion contracture was present. Subsequently, serial casting was used to achieve full extension at four weeks after surgery. Excellent function and patient satisfaction were observed at two years of follow up. CONCLUSION: The new protocol of total knee arthroplasty with subsequent serial casting seems to be an efficient solution for knee flexion contractures greater than 80 degrees . This report adds to the very small number of reported cases of adult-onset Still's disease with severe knee flexion contractures and describes a patient who was successfully treated with a new protocol. PMID- 26860206 TI - Environmental contamination and transmission of Ascaris suum in Danish organic pig farms. AB - BACKGROUND: Although Ascaris suum is the most common pig nematode, the on-farm transmission dynamics are not well described. METHODS: We performed a 1-year field study on five organic pig farms, mapping egg contamination levels in pens and pasture soil as well as faecal egg counts in starter pigs, finisher pigs, dry and lactating sows. The uppermost bedding material was sampled from three pen areas (resting, intermediate and latrine) of shallow and deep litter pens. RESULTS: Ascaris suum was found on all farms. Averaged across farm and season, the prevalence of A. suum was 48, 64, 28 and 15% in starters, finishers, dry and lactating sows, respectively. For starters and finishers, the prevalence varied with season increasing towards the end of the year when 83-96% of finishing pigs from each farm had fresh liver white spots. Farrowing pastures were contaminated with a mean of 78-171 larvated eggs/kg dry soil depending on farm, while pastures for starter pigs contained 290-5397 larvated eggs/kg dry soil. The concentration of eggs in soil was highest in the autumn. Indoors, all pen areas were contaminated with A. suum eggs at comparable levels for shallow and deep litter. Overall there were 106, 445 and 1331 eggs/g dry straw in the resting, intermediate and latrine areas, respectively. However, more eggs were undergoing development in resting areas (44%) compared to intermediate (33%) and latrine areas (13%). Irrespective of area, more eggs were undergoing development in the autumn, but overall there were very few fully developed (i.e., infective) eggs in the bedding material. Laboratory embryonation of eggs from the bedding material nevertheless revealed that an overall mean of 79% of the eggs were viable. CONCLUSION: The organic pigs of all ages were continuously exposed to A. suum, but mainly younger animals were infected. Deep litter appeared to be a less important source of A. suum eggs than previously believed compared to shallow litter. Long-term pasture rotation to eliminate pasture contamination was not possible, and control programs should therefore include thorough cleaning indoors and composting/long-term storage of bedding material and manure to inactivate eggs and reduce transmission to pigs. PMID- 26860207 TI - Effect of heterocyclic capping groups on the self-assembly of a dipeptide hydrogel. AB - The mechanism and design rules associated with the self-assembly of short peptides into hydrogels is currently not well understood. In this work, four diphenylalanine-based peptides have been synthesised, bearing heterocyclic capping groups which have different degrees of hydrogen bonding potential and nitrogen substitution. For these four peptides, zeta potential and electrical impedance spectroscopy measurements were undertaken to monitor gelation, with the impedance data showing different gelation times for each peptide hydrogel. Through a combination of atomic force microscopy and rheological measurmeents, including dynamic strain and frequency sweeps, and thixotropic tests, the relationship between the mechanism of self-assembly in these hydrogels and their macroscopic behaviour can be established. It is observed that the degree of nitrogen substitution affects the self-assembly mechanisms of the hydrogels and as such, that there is an interplay between branching and bundling self-assembly pathways that are responsible for the final properties of each hydrogel. PMID- 26860209 TI - Removal of inverted papilloma from the frontal recess: how we do it. PMID- 26860208 TI - Behavior of platinum(iv) complexes in models of tumor hypoxia: cytotoxicity, compound distribution and accumulation. AB - Hypoxia in solid tumors remains a challenge for conventional cancer therapeutics. As a source for resistance, metastasis development and drug bioprocessing, it influences treatment results and disease outcome. Bioreductive platinum(iv) prodrugs might be advantageous over conventional metal-based therapeutics, as biotransformation in a reductive milieu, such as under hypoxia, is required for drug activation. This study deals with a two-step screening of experimental platinum(iv) prodrugs with different rates of reduction and lipophilicity with the aim of identifying the most appropriate compounds for further investigations. In the first step, the cytotoxicity of all compounds was compared in hypoxic multicellular spheroids and monolayer culture using a set of cancer cell lines with different sensitivities to platinum(ii) compounds. Secondly, two selected compounds were tested in hypoxic xenografts in SCID mouse models in comparison to satraplatin, and, additionally, (LA)-ICP-MS-based accumulation and distribution studies were performed for these compounds in hypoxic spheroids and xenografts. Our findings suggest that, while cellular uptake and cytotoxicity strongly correlate with lipophilicity, cytotoxicity under hypoxia compared to non-hypoxic conditions and antitumor activity of platinum(iv) prodrugs are dependent on their rate of reduction. PMID- 26860210 TI - I-SceI enzyme mediated integration (SEMI) for fast and efficient gene targeting in Trichoderma reesei. AB - We previously showed that creation of a double strand DNA break (DSB) by expressing I-SceI in an engineered Trichoderma reesei (Hypocrea jecorina) strain containing a I-SceI recognition site improved transformation and homologous integration efficiencies. In this study, we further improved homologous integration frequencies by combining I-SceI mediated double strand break with disruption of the tku70 gene. The inability of the tku70 mutant to repair a I SceI mediated DSB via NHEJ was used to force integration of an expression cassette with homologous flanks surrounding the DSB site. Besides expressing I SceI from a plasmid, we also show that adding I-SceI enzyme during transformation was successful to generate DSBs. The I-SceI enzyme mediated integration, or SEMI, in combination with a Deltatku70 mutant has a synergistic effect on homologous recombination efficiencies as 90-100% of the transformants exhibited integration of the expression cassette at the homologous site. PMID- 26860211 TI - ksRepo: a generalized platform for computational drug repositioning. AB - BACKGROUND: Repositioning approved drug and small molecules in novel therapeutic areas is of key interest to the pharmaceutical industry. A number of promising computational techniques have been developed to aid in repositioning, however, the majority of available methodologies require highly specific data inputs that preclude the use of many datasets and databases. There is a clear unmet need for a generalized methodology that enables the integration of multiple types of both gene expression data and database schema. RESULTS: ksRepo eliminates the need for a single microarray platform as input and allows for the use of a variety of drug and chemical exposure databases. We tested ksRepo's performance on a set of five prostate cancer datasets using the Comparative Toxicogenomics Database (CTD) as our database of gene-compound interactions. ksRepo successfully predicted significance for five frontline prostate cancer therapies, representing a significant enrichment from over 7000 CTD compounds, and achieved specificity similar to other repositioning methods. CONCLUSIONS: We present ksRepo, which enables investigators to use any data inputs for computational drug repositioning. ksRepo is implemented in a series of four functions in the R statistical environment under a BSD3 license. Source code is freely available at http://github.com/adam-sam-brown/ksRepo. A vignette is provided to aid users in performing ksRepo analysis. PMID- 26860212 TI - Human bromethalin exposures reported to a U.S. Statewide Poison Control System. AB - BACKGROUND: Bromethalin is an increasingly used alternative to long-acting anticoagulant and cholecalciferol rodenticides. There are few reports of human exposures, and no existing professional society guidelines on medical management of bromethalin ingestions. The aim of this retrospective data review is to characterize bromethalin exposures reported to the California Poison Control System (CPCS) between 1997 and 2014. METHODS: This is an observational retrospective case review of our statewide poison control system's electronic medical records. Following Institutional Board Review and Research Committee approvals, poison center exposures related to bromethalin were extracted using substance code and free text search strategies. Case notes of bromethalin exposures were reviewed for demographic, clinical, laboratory, and outcome information; inclusion criteria for the study was single-substance, human exposure to bromethalin. RESULTS: There were 129 calls related to human bromethalin exposures (three cases met exclusion criteria). The age range of cases was 7 months-90 years old, with the majority of exposures (89 cases; 70.6%), occurring in children younger than 5 years of age (median age of 2 years). Most exposures occurred in the pediatric population as a result of exploratory oral exposure. One hundred and thirteen patients (89.7%) had no effects post exposure, while 10 patients (7.9%) had a minor outcome. Adverse effects were minor, self-limited, and mostly gastrointestinal upset. There were no moderate, major, or fatal effects in our study population. The approximate ingested dose, available in six cases, ranged from 0.067 mg/kg to 0.3 mg/kg (milligrams of bromethalin ingested per kilogram of body weight), and no dose symptom threshold could be established from this series. Exposures were not confirmed through urine or serum laboratory testing. DISCUSSION: The prognosis for most accidental ingestions appears to be excellent. However, bromethalin exposures may result in a higher number of symptomatic patients than long-acting anticoagulant agents. Parents, physicians and poison control specialists are encouraged to maintain a high index of suspicion for bromethalin-related complications in all cases of rodenticide exposures. CONCLUSIONS: Accidental bromethalin exposures in children appear to be self-limited in toxicity. Additional studies are warranted to determine whether more severe effects are precipitated when larger amounts are involved, particularly in suicidal ingestion. PMID- 26860213 TI - Water-Holding and Transport Properties of Skin Stratum Corneum of Infants and Toddlers Are Different from Those of Adults: Studies in Three Geographical Regions and Four Ethnic Groups. AB - BACKGROUND/OBJECTIVE: Epidermal structure, function, and composition are different in white infants and adults. We investigated whether ethnicity and location contribute to differences in functional and clinical measurements of skin barrier function during the first years of life and in adults. METHODS: Children (n = 397, ages 3-49 mos) and women (n = 117, mean age 31 yrs) were enrolled at independent centers in Beijing, China (ethnic Chinese), Skillman, New Jersey (white, African American), and Mumbai, India (ethnic South Asian). Water barrier properties of the stratum corneum were assessed using high-frequency conductance and transepidermal water loss (TEWL) on the dorsal forearm and upper inner arm. Digital imaging was used to evaluate facial erythema and scaling. RESULTS: Despite differences in local climate, TEWL was similar in adults. In children, conductance and TEWL decreased monotonically from age 3 months to 4 years. In children from Beijing, TEWL values were higher in both arm locations than in children in Mumbai and Skillman. No significant differences were observed in TEWL or conductance between the white and African American groups. CONCLUSION: In general, TEWL and conductance were greater on the upper inner arm than the dorsal forearm. Erythema and scaling were observed most often in subjects from Beijing and most infrequently in subjects from Mumbai. Stratum corneum water barrier properties were different in children and adults. Although there may be differences in these properties between ethnic groups in childhood, TEWL values were similar in adults across the three geographic locations and four ethnicities. PMID- 26860215 TI - [Open minds first, then the ICU doors]. PMID- 26860214 TI - Advance care planning in chronic kidney disease: A survey of current practice in Australia. AB - AIM: Advance care planning (ACP) in nephrology is widely advocated but not always implemented. The aims of this study were to describe current ACP practice and identify barriers/facilitators and perceived need for health professional education and chronic kidney disease (CKD)-specific approaches. METHODS: An anonymous cross-sectional survey was administered online. Nephrology health professionals in Australia and New Zealand were recruited via professional societies, email lists and nephrology conferences. Multiple regression explored the influence of respondents' attributes on extent of involvement in ACP and willingness to engage in future. RESULTS: A total of 375 respondents included nephrologists (23%), nurses (65%), social workers (4%) and others (8%) with 54% indicated that ACP at their workplace was performed ad hoc and 61% poorly. Perceived barriers included patient/family discomfort (84%), difficulty engaging families (83%), lack of clinician expertise (83%) and time (82%), health professional discomfort (72%), cultural/language barriers (65%), lack of private space (61%) and lack of formal policy/procedures (60%). Respondents overwhelmingly endorsed the need for more dialysis-specific ACP programs (96%) and education (95%). Whilst 85% thought ACP would be optimally performed by specially trained staff, comments emphasized that all clinicians should have a working proficiency. Respondents who were more willing to engage in future ACP tended to be non-physicians (odds ratio (OR) 4.96, 95% confidence intervals (CI) 1.74-14.07) and reported a greater need for CKD-specific ACP materials (OR 10.88, 95% CI 2.38-49.79). CONCLUSION: Advance care planning in nephrology needs support through education and CKD-specific resources. Endorsement by nephrologists is important. A multidisciplinary approach with a gradient of ACP expertise is also recommended. PMID- 26860216 TI - [The SPLIT trial: Anything new in critical care fluid therapy?]. PMID- 26860218 TI - Cerebral microbleeds in idiopathic normal pressure hydrocephalus. AB - BACKGROUND: A vascular disease could be involved in pathophysiology of normal pressure hydrocephalus (INPH). If so, there should be an association between INPH and cerebral microbleeds (CMB). This study aims to analyze if CMB are associated with INPH. METHODS: In this case-control study we included 14 patients with INPH (mean age 76 years, 60 % female) and 41 healthy controls (HeCo; mean age 71 years, 60 % female). All were investigated with magnetic resonance imaging (MRI) using a T2*-sequence. The MRI exams were reviewed by two neuroradiologists for the presence of CMBs; the prevalence of findings of two or more CMBs was compared between INPH group and control group. After investigation, INPH patients underwent shunt surgery. RESULTS: Two or more CMB were detected more frequently in the INPH group compared to HeCo (n = 6, 43 % vs. n = 4, 10 %; p = 0.01). Among the participants where MRI revealed CMB, the number of CMB was higher among the INPH patients than the HeCo (median 8; IQR 2-34 vs. median 1; IQR 1-2; p = 0.005). CONCLUSIONS: This study supports a vascular component to the pathophysiology of INPH. PMID- 26860217 TI - Associations between advanced cancer patients' survival and family caregiver presence and burden. AB - We conducted a randomized controlled trial (RCT) of an early palliative care intervention (ENABLE: Educate, Nurture, Advise, Before Life Ends) for persons with advanced cancer and their family caregivers. Not all patient participants had a caregiver coparticipant; hence, we explored whether there were relationships between patient survival, having an enrolled caregiver, and caregiver outcomes prior to death. One hundred and twenty-three patient-caregiver dyads and 84 patients without a caregiver coparticipant participated in the ENABLE early versus delayed (12 weeks later) RCT. We collected caregiver quality of-life (QOL), depression, and burden (objective, stress, and demand) measures every 6 weeks for 24 weeks and every 3 months thereafter until the patient's death or study completion. We conducted survival analyses using log-rank and Cox proportional hazards models. Patients with a caregiver coparticipant had significantly shorter survival (Wald = 4.31, HR = 1.52, CI: 1.02-2.25, P = 0.04). After including caregiver status, marital status (married/unmarried), their interaction, and relevant covariates, caregiver status (Wald = 6.25, HR = 2.62, CI: 1.23-5.59, P = 0.01), being married (Wald = 8.79, HR = 2.92, CI: 1.44-5.91, P = 0.003), and their interaction (Wald = 5.18, HR = 0.35, CI: 0.14-0.87, P = 0.02) were significant predictors of lower patient survival. Lower survival in patients with a caregiver was significantly related to higher caregiver demand burden (Wald = 4.87, CI: 1.01-1.20, P = 0.03) but not caregiver QOL, depression, and objective and stress burden. Advanced cancer patients with caregivers enrolled in a clinical trial had lower survival than patients without caregivers; however, this mortality risk was mostly attributable to higher survival by unmarried patients without caregivers. Higher caregiver demand burden was also associated with decreased patient survival. PMID- 26860219 TI - Thoracic lymphadenopathy in benign diseases: A state of the art review. AB - Lymphadenopathy is a common radiological finding in many thoracic diseases and may be caused by a variety of infectious, inflammatory, and neoplastic conditions. This review aims to describe the patterns of mediastinal and hilar lymphadenopathy found in benign diseases in immunocompetent patients. Computed tomography is the method of choice for the evaluation of lymphadenopathy, as it is able to demonstrate increased size of individual nodes, abnormalities of the interface between the mediastinum and lung, invasion of surrounding fat, coalescence of adjacent nodes, obliteration of the mediastinal fat, and hypo- and hyperdensity in lymph nodes. Intravenous contrast enhancement may be needed to help distinguish nodes from vessels. The most frequent infections resulting in this finding are tuberculosis and fungal disease (particularly histoplasmosis and coccidioidomycosis). Sarcoidosis is a relatively frequent cause of lymphadenopathy in young adults, and can be distinguished from other diseases - especially when enlarged lymph nodes are found to be multiple and symmetrical. Other conditions discussed in this review are silicosis, drug reactions, amyloidosis, heart failure, Castleman's disease, viral infections, and chronic obstructive pulmonary disease. PMID- 26860220 TI - Psychometric properties of the newly translated creole multidimensional scale of perceived social support (MSPSS) and perceived adequacy of resource scale (PARS) and the relationship between perceived social support and resources in Haitian mothers in the US. AB - BACKGROUND: Low income postpartum mothers with little to no social support have increased maternal and infant morbidity and mortality, especially those with limited English proficiency and limited accesses to resources. Haitians, a growing minority in the US are an understudied population excluded from most studies due to the lack of instruments in Creole. The most widely used instruments for measuring social support, the Multidimensional Scale of Perceived Social Support (MSPSS) and Perceived Adequacy of Resource Scale (PARS), are not available in Creole. Currently, there are no published studies on the psychometric properties of the MSPSS or the PARS in Creole. Data from Haitian mothers are needed to identify potential postpartum mothers and infants most at risk of developing adverse maternal and infant outcomes from a lack of social support and perceived resources. The purpose of this study is to test the psychometrics of the newly-translated Creole instruments of the MSPSS and PARS with a sample of bilingual (Creole/English) mothers. METHODS: The MSPSS and PARS were translated and back translated from English to Creole. The adapted Creole versions of the instruments were tested using a convenience sample. A total of 85 Haitian mothers' completed both instruments in Creole and English 2 weeks apart. RESULT: Internal consistency reliability and stability were strong for both the MSPSS and PARS (.91-.99). The two instruments had strong reliability and validity for the translated Creole versions and similar to the English versions. CONCLUSION: The MSPSS and PARS are a valid measure of perceived social support and resources. Psychometric findings suggest that the newly translated Creole versions are good representations of the English versions indicating the translation process was successful. The newly translated instruments available in Creole provide non-English speaking Haitian mothers the opportunity to participate in studies. PMID- 26860221 TI - Harnessing B cells in immunotherapy. PMID- 26860222 TI - EPO induces changes in synaptic transmission and plasticity in the dentate gyrus of rats. AB - Erythropoietin has shown wide physiological effects on the central nervous system in animal models of disease, and in healthy animals. We have recently shown that systemic EPO administration 15 min, but not 5 h, after daily training in a water maze is able to induce the recovery of spatial memory in fimbria-fornix chronic lesioned animals, suggesting that acute EPO triggers mechanisms which can modulate the active neural plasticity mechanism involved in spatial memory acquisition in lesioned animals. Additionally, this EPO effect is accompanied by the up-regulation of plasticity-related early genes. More remarkably, this time dependent effects on learning recovery could signify that EPO in nerve system modulate specific living-cellular processes. In the present article, we focus on the question if EPO could modulate the induction of long-term synaptic plasticity like LTP and LTD, which presumably could support our previous published data. Our results show that acute EPO peripheral administration 15 min before the induction of synaptic plasticity is able to increase the magnitude of the LTP (more prominent in PSA than fEPSP-Slope) to facilitate the induction of LTD, and to protect LTP from depotentiation. These findings showing that EPO modulates in vivo synaptic plasticity sustain the assumption that EPO can act not only as a neuroprotective substance, but is also able to modulate transient neural plasticity mechanisms and therefore to promote the recovery of nerve function after an established chronic brain lesion. According to these results, EPO could be use as a molecular tool for neurorestaurative treatments. PMID- 26860223 TI - Editorial: What's new this month? PMID- 26860224 TI - DeRmpath & Clinic Granular cell tumor of the vulva. PMID- 26860225 TI - And next... Adnexa: Frontal Fibrosing Alopecia. PMID- 26860226 TI - sQuiz editorial: Latent tuberculosis infection: Update of diagnosis before the introduction of biologic drugs. PMID- 26860229 TI - Assessment of provider attitudes toward #naloxone on Twitter. AB - BACKGROUND: As opioid overdose rates continue to pose a major public health crisis, the need for naloxone treatment by emergency first responders is critical. Little is known about the views of those who administer naloxone. The current study examines attitudes of health professionals on the social media platform Twitter to better understand their perceptions of opioid users, the role of naloxone, and potential training needs. METHODS: Public comments on Twitter regarding naloxone were collected for a period of 3 consecutive months. The occupations of individuals who posted tweets were identified through Twitter profiles or hashtags. Categories of emergency service first responders and medical personnel were created. Qualitative analysis using a grounded theory approach was used to produce thematic content. The relationships between occupation and each theme were analyzed using Pearson chi-square statistics and post hoc analyses. RESULTS: A total of 368 individuals posted 467 naloxone related tweets. Occupations consisted of professional first responders such as emergency medical technicians (EMTs), firefighters, and paramedics (n = 122); law enforcement officers (n = 70); nurses (n = 62); physicians (n = 48); other health professionals including pharmacists, pharmacy technicians, counselors, and social workers (n = 31); naloxone-trained individuals (n = 12); and students (n = 23). Primary themes included burnout, education and training, information seeking, news updates, optimism, policy and economics, stigma, and treatment. The highest levels of burnout, fatigue, and stigma regarding naloxone and opioid overdose were among nurses, EMTs, other health care providers, and physicians. In contrast, individuals who self-identified as "naloxone-trained" had the highest optimism and the lowest amount of burnout and stigma. CONCLUSIONS: Provider training and refinement of naloxone administration procedures are needed to improve treatment outcomes and reduce provider stigma. Social networking sites such as Twitter may have potential for offering psychoeducation to health care providers. PMID- 26860230 TI - Exploring Communication Challenges Between Nurses and Mechanically Ventilated Patients in the Intensive Care Unit: A Structured Review. AB - BACKGROUND: Mechanical ventilation is a necessary procedure for patients with a range of illnesses and conditions. Mechanical ventilation affects voice production, leaving patients unable to communicate their needs with nurses and family. The communication difficulty causes distress, frustration, and anger if not attended to. AIMS: This structured review sought to identify communication challenges which exist between nurses and mechanically ventilated patients in intensive care units (ICU) and hence explore possible solutions to improve these communication challenges. METHODS: A electronic search of MEDLINE, CINAHL, and PsycINFO was conducted to identify relevant literature on nurse-patient communication challenges in the ICU published between January 2005 and December 2014. Studies meeting the inclusion criteria were retrieved in full, reviewed, and study quality assessed. RESULTS: Six studies were identified for inclusion in the review. Analysis identified five core influences on communication in the ICU: patient's consciousness level, nature of nurse-patient interactions, communication methods, staff skills and perceptions, and the intensive care physical environment. LINKING EVIDENCE TO ACTION: An evidence-based and multifactorial communication intervention encompassing staff skills development and training, development of relevant patient materials or devices and collaborations with relevant health professionals like speech and language therapists has the potential to improve nurse-patient communication in the ICU and hence improve patient outcomes. PMID- 26860231 TI - Stria vascularis and cochlear hair cell changes in syphilis: A human temporal bone study. AB - OBJECTIVE: To observe any changes in stria vascularis and cochlear hair cells in patients with syphilis. MATERIALS AND METHODS: We examined 13 human temporal bone samples from 8 patients with syphilis (our syphilis group), as well as 12 histopathologically normal samples from 9 age-matched patients without syphilis (our control group). We compared, between the two groups, the mean area of the stria vascularis (measured with conventional light microscopy connected to a personal computer) and the mean percentage of cochlear hair cell loss (obtained from cytocochleograms). RESULTS: In our syphilis group, only 1 (7.7%) of the 13 samples had precipitate in the endolymphatic or perilymphatic spaces; 8 (61.5%) of the samples revealed the presence of endolymphatic hydrops (4 cochlear, 4 saccular). The mean area of the stria vascularis did not significantly differ, in any turn of the cochlea, between the 2 groups (P>0.1). However, we did find significant differences between the 2 groups in the mean percentage of outer hair cells in the apical turn (P<0.026) and in the mean percentage of inner hair cells in the basal (P=0.001), middle (P=0.004), and apical (P=0.018) turns. In 7 samples in our syphilis group, we observed either complete loss of the organ of Corti or a flattened organ of Corti without any cells in addition to the absence of both outer and inner hair cells. CONCLUSION: In this study, syphilis led either to complete loss of the organ of Corti or to significant loss of cochlear hair cells, in addition to cochleosaccular hydrops. But the area of the stria vascularis did not change. PMID- 26860232 TI - The role of bacteriological studies in the management of peritonsillar abscess. AB - OBJECTIVE: Since most patients with peritonsillar abscess (PTA) can be successfully treated with surgical drainage and empirical antibiotic therapy, routine bacteriologic studies for all patients with PTA may be unnecessary. This study tried to evaluate which patients with PTA should certainly undergo bacteriologic studies. METHODS: Hundred consecutive patients with PTA were treated and underwent culture tests of purulent contents obtained by surgical drainage between April 2008 and December 2013. RESULTS: In 62 of the 100 patients, 71 pathogenic bacteria were identified; 61 (86%) were Gram-positive cocci (GPC), 8 (11%) were Gram-negative rods (GNR), and 6 (8%) were anaerobes. Normal flora were isolated in 27 patients, and culture results were negative in 11 patients. Although not significant, primary (without prior antibiotic therapy) case (odds ratio (OR)=2.19; 95% CI, 0.95-5.05) and laryngeal edema (OR=2.04; 95% CI, 0.82-5.03) showed a tendency of associations with detection of pathogenic bacteria. After taking into account interactions between smoking habit and laryngeal edema, the covariate-adjusted OR for non-smokers with laryngeal edema was significant and showed a strong relationship (OR=7.43; 95% confidence interval, 1.05-52.73) compared to non-smokers without laryngeal edema. CONCLUSION: Although empirical antibiotic therapy was effective for most of the PTA patients, bacteriologic studies might be indispensable for the patients with laryngeal edema considering the failure of the first treatments. Particularly, the culture tests may be useful for non-smokers with laryngeal edema. PMID- 26860233 TI - Role of cancer stem cell in radioresistant head and neck cancer. AB - OBJECTIVE: Radioresistance is the main determinant of treatment outcome in head and neck cancer. The aim of this study was to establish radioresistant head and neck cancer cell lines and isolate cancer stem cells from them to investigate the role of cancer stem cells in radioresistant head and neck cancer. METHODS: To induce radioresistant cell lines, radiation was delivered to SCC15, SCC25, and QLL1 cells with an accumulated dosage of 60Gy over 30 cycles of irradiation. After a total of 60Gy of irradiation, the radioresistance of irradiated cancer cells was verified by MTT assay. The radioresistant cells were cultured in serum free medium in ultra-low-attachment culture flasks to induce sphere-forming cells. Then, sphere-forming cells were analyzed using Western blotting to identify the expression of stem cell markers, such as Nanog and Sox-2. RESULTS: The MTT assay of cell viability showed more radioresistance in the irradiated cancer cell lines than in the non-irradiated cancer cell lines. Sphere-forming cells were identified in all three cancer cell lines 3-5 days after serum deprivation. All sphere-forming cells from the three cancer cell lines expressed stem cell markers. Sphere-forming cells showed more radioresistance than monolayer cells after irradiation by colony forming assay. CONCLUSION: Cancer stem cells seem to play an important role in the radioresistance of head and neck cancer. Further research is required to find a precise mechanism of radioresistance related to cancer stem cells. PMID- 26860234 TI - Cavernous sinus thrombosis secondary to aspergillus granuloma: A case report and review of the literature. AB - Cavernous sinus thrombosis is a rare but serious complication of sphenoid aspergillosis. The rarity of this pathology makes its diagnostic very difficult on a clinical, biological and radiological sense. The authors present a case of cavernous sinus thrombosis with ipsilateral internal carotid artery thrombosis secondary to a non-invasive sphenoid aspergillosis in an immunocompetent host, responsible of a cavernous syndrome associated to a Claude Bernard Horner syndrome. One year after surgery, the patient is still asymptomatic without recurrence. Diagnostic modalities are detailed and several management of this pathology are compared. Surgery is essential in a diagnostic and therapeutic sense. There is no evidence of the interest of adjuvant therapies such as antibiotic and anticoagulation. Concerning the antifungal treatment, the attitude towards a non-invasive sphenoid aspergillosis in an immunocompetent host is unclear. PMID- 26860235 TI - Intralesional cidofovir injection for recurrent respiratory papillomatosis in Japan. AB - OBJECTIVE: The treatment of recurrent respiratory papillomatosis (RRP) continues to be difficult. Adjuvant pharmacological treatment is increasingly being used, and intralesional cidofovir injection remains the leading option. Almost all papers regarding the treatment come from the United States and Europe. The present study demonstrated it for the first time from Asia. METHODS: Ten patients with RRP were treated with intralesional cidofovir injection. The severity of papillomatosis and adverse events including blood leukocytes, blood neutrophils, and serum creatinine were evaluated before and after the completion of treatment. RESULTS: Human papillomavirus (HPV) type 6 was detected in nine patients, and no types of HPV were detected in a remaining patient. Severity scores significantly improved after treatment (p=0.005). However, complete resolution was achieved in only one patient. No significant differences were observed between before and after treatment with respect to adverse events (p=0.866 for blood leukocytes, p=0.866 for blood neutrophils, and p=0.933 for serum creatinine). Squamous cell carcinoma occurred three and half years after the completion of treatment in a patient without HPV detection. However, the link between cidofovir and the occurrence of carcinoma in the case remains questionable. CONCLUSION: This initial report of intralesional cidofovir injection for RRP from Asia demonstrated acceptable efficacy without obvious adverse events. However, the uncontrolled spread of this treatment should be avoided, and eighteen statements approved by the task force of the United States should be referred to while planning this treatment. PMID- 26860236 TI - Solid cancer incidence among Chinese medical diagnostic x-ray workers, 1950-1995: Estimation of radiation-related risks. AB - The objective of this study was to estimate solid cancer risk attributable to long-term, fractionated occupational exposure to low doses of ionizing radiation. Based on cancer incidence for the period 1950-1995 in a cohort of 27,011 Chinese medical diagnostic X-ray workers and a comparison cohort of 25,782 Chinese physicians who did not use X-ray equipment in their work, we used Poisson regression to fit excess relative risk (ERR) and excess absolute risk (EAR) dose response models for incidence of all solid cancers combined. Radiation dose reconstruction was based on a previously published method that relied on simulating measurements for multiple X-ray machines, workplaces and working conditions, information about protective measures, including use of lead aprons, and work histories. The resulting model was used to estimate calendar year specific badge dose calibrated as personal dose equivalent (Sv). To obtain calendar year-specific colon doses (Gy), we applied a standard organ conversion factor. A total of 1,643 cases of solid cancer were identified in 1.45 million person-years of follow-up. In both ERR and EAR models, a statistically significant radiation dose-response relationship was observed for solid cancers as a group. Averaged over both sexes, and using colon dose as the dose metric, the estimated ERR/Gy was 0.87 (95% CI: 0.48, 1.45), and the EAR was 22 per 10(4)PY-Gy (95% CI: 14, 32) at age 50. We obtained estimates of the ERR and EAR of solid cancers per unit dose that are compatible with those derived from other populations chronically exposed to low dose-rate occupational or environmental radiation. PMID- 26860237 TI - Automodification of PARP and fatty acid-based membrane lipidome as a promising integrated biomarker panel in molecular medicine. AB - AIM: Establishing by statistical analyses whether the analyses of auto-modified poly(ADP-ribose)polymerase and erythrocyte membrane fatty acid composition (Fat Profile((r))), separately or in tandem, help monitoring the physio-pathology of the cell, and correlate with diseases, if present. PATIENTS & METHODS: Ninety five subjects were interviewed and analyzed blindly. Blood lymphocytes and erythrocytes were prepared to assay poly(ADP-ribose)polymerase automodification and fatty acid based membrane lipidome, respectively. RESULTS: Poly(ADP ribose)polymerase automodification levels confirmed their correlation with DNA damage extent, and allowed monitoring disease activity, upon surgical/therapeutic treatment. Membrane lipidome profiles showed lipid unbalance mainly linked to inflammatory states. Statistically both tests were separately significant, and correlated each other within some pathologies. CONCLUSION: In the laboratory routine, both tests, separately or in tandem, might be a preliminary and helpful step to investigate the occurrence of a given disease. Their combination represents a promising integrated panel for sensible, noninvasive and routine health monitoring. PMID- 26860238 TI - Effects of dietary acidifiers on growth, hematology, immune response and disease resistance of Nile tilapia, Oreochromis niloticus. AB - Organic acids or their salts can be used as feed additives in aquaculture. This study was conducted to evaluate the use of a mixture of formic acid, propionic acid and calcium propionate compared with oxytetracycline (OTC). A total of 720 apparently healthy Oreochromis niloticus fingerlings with an average body weight of 28.8 +/- 0.14 g (mean +/- SE) were randomly divided into four equal groups (G1, G2, G3and G4). G1 was fed a basal diet with no additive as the control group, while G2 and G3 were fed a formic and propionic acid/salt mixture in 1 and 2 g/kg, respectively. G4 was fed OTC (0.5 g/kg). Each group was subdivided into tow subgroups A and B (30 fish/subgroup) in triplicate. The first subgroup was used to evaluate growth performance, hematology and body composition for 60 d. The second subgroup was used to examine immunity, gut microbiota and resistance to infection for 30 d. At the end of the feeding period (60 d), G3 had significant improvements in final body weight (FBW), weight gain (WG), specific growth rate (SGR) and food conversion ratio (FCR) compared with other groups. The total erythrocyte count, hemoglobin content, platelet count, hematocrit, mean corpuscular hemoglobin and total leukocyte count were significantly increased in G3 and G2 compared with G1 and G4. Mean corpuscular volum, lymphocyte and neutrophil percentages had the highest significant improvement in G3. There were no significant differences among the groups in mean corpuscular hemoglobin concentration and monocyte percentage. The protein and fat contents of the whole body were the highest in G3. The widest inhibition zones against Aeromonas sobria were at the 30, 40 and 50% concentrations of acidifiers, which were equivalent to OTC (30 MUg). G3 showed the lowest total gastrointestinal bacterial counts, followed by G2. After 15 and 30 d, G3 had the highest serum killing, lysozyme and nitric oxide activities. Serum lysozyme activity and nitric oxide assay had no significant difference between G1 and G2 after 30 d. The lowest immune parameters were recorded in G4. After 30 d, the highest expression of interleukin-1beta and tumor necrosis factor-alpha in the liver and kidney were found in G3. The best protection against challenged Aeromonas sobria was in G3, followed by G2 and G4. Dietary supplementation with a combination of formic acid, propionic acid and calcium propionate improves the performance of Nile tilapia. PMID- 26860240 TI - Solitary rectal metastasis from renal cell carcinoma treated by endoscopic resection. PMID- 26860239 TI - Cytokines elevated in patients with HBV-related acute-on-chronic liver failure promote NK cell mediated cytotoxicity through TRAIL. AB - BACKGROUND AND AIMS: The role of NK cells on inducing liver injury in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) is not well understood. The aim of this study was to determine the cytotoxicity of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-expressed NK cells from HBV-ACLF patients and facilitate a better understanding of the immune pathogenesis of HBV-ACLF. METHODS: Peripheral blood samples were obtained from HBV-ACLF patients, mild chronic hepatitis B (CHB) patients and healthy controls (HC). Circulating NK cells phenotype was determined using flow cytometry. Serum cytokine concentrations were ascertained using the CBA Inflammation kit. Cell apoptosis was analyzed using the FITC-annexin V Apoptosis Detection Kit. RESULTS: Peripheral NK cells from HBV-ACLF expressed higher levels of TRAIL than those from CHB and HC. Expression of TRAIL on NK cells was correlated positively with serum IL-6 and IL-8 concentrations in HBV-ACLF patients, which is further confirmed by cytokines stimulation in vitro. NK cells caused a significant increase of apoptotic hepatocytes, and further increased the frequency of apoptosis in IL-6 and IL8-stimulated hepatocytes; the apoptosis was then inhibited partially by an anti-TRAIL monoclonal antibody. CONCLUSION: These results suggested that inflammation cytokines elevated in patients with HBV-ACLF may promote NK cell mediated cytotoxicity through TRAIL pathway. PMID- 26860241 TI - Transport Mechanisms of Solid Lipid Nanoparticles across Caco-2 Cell Monolayers and their Related Cytotoxicology. AB - Solid lipid nanoparticles (SLNs) have been extensively investigated and demonstrated to be a potential nanocarriers for improving oral bioavailability of many drugs. However, the molecular mechanisms related to this discovery are not yet understood. Here, the molecular transport mechanisms of the SLNs crossing simulative intestinal epithelial cell monolayers (Caco-2 cell monolayers) were studied. The cytotoxicology results of the SLNs in Caco-2 cells demonstrated that the nanoparticles had low cytotoxicity, had no effect on the integrity of the cell membrane, did not induce oxidative stress, and could significantly reduce cell membrane fluidity. The endocytosis of the SLNs was time-dependent, and their delivery was energy-dependent. For the first time, the transport of the SLNs was directly verified to be a vesicle-mediated process. The internalization of the SLNs was mediated by macropinocytosis pathway and clathrin- and caveolae (or lipid raft)-related routes. Transferrin-related endosomes, lysosomes, endoplasmic reticulum (ER), and Golgi apparatus were confirmed to be the main destinations of the SLNs in Caco-2 cells. As for the transport of the SLNs in Caco-2 cell monolayers, the results demonstrated that the SLNs transported to the basolateral side were intact, and the transport of the nanoparticles did not destroy the structure of tight junctions. The transcytosis of the SLNs across the Caco-2 cell monolayer was demonstrated to be mediated by the same routes as that in the endocytosis study. The ER, Golgi apparatus, and microtubules were confirmed to be important for the transport of the SLNs to both the basolateral and apical membrane sides. This study provides a more thoroughly understand of SLNs transportation crossing intestinal epithelial cell monolayers and could be beneficial for the fabrication of SLNs. PMID- 26860242 TI - Structural characterization and profiling of lyso-phospholipids in fresh and in thermally stressed mussels by hydrophilic interaction liquid chromatography electrospray ionization-Fourier transform mass spectrometry. AB - The separation efficiency of hydrophilic interaction liquid chromatography and the high resolution/accuracy of electrospray ionization-Fourier transform MS were successfully applied to the detailed characterization of lyso phosphatidylcholines (LPCs) and lyso-phosphatidylethanolamines (LPEs) contained in the lipid extracts of Mytilus galloprovincialis (Mediterranean mussel). As a result, 57 LPCs, including regio- and positional isomers, and 45 LPEs, including acyl and plasma(e)nyl species, were identified. Four lyso-phosphonocholines were also identified among mussel Lyso-Phospholipids. To the best of our knowledge this represents the first characterization, at a molecular level, ever reported for LPEs in mussels. No significant variation was observed in the composition of both LPCs and LPEs when mussels were refrigerated at +4 degrees C for up to 48 h, i.e. under conditions usually employed for seafood transportation and storage. Treatments mimicking more severe thermal stresses, namely eight day-refrigeration at + 4 degrees C, two week-freezing at -15 degrees C and 6 h-storage at 25 degrees C, resulted in a significant increase in the molar abundance of LPCs and LPEs (expressed with respect to that of their precursors, PCs and PEs, respectively) and was accompanied by the death of all or part of the molluscs. These results were interpreted invoking the generation of lyso-phospholipids, mediated by endogenous phospholipases, as an intermediate process toward the partial replacement of side chains in phospholipids, perhaps functional to a better adaptation of mussels to adverse temperature conditions. Interestingly, the relative abundances of specific compounds belonging to the LPC and LPE classes were found to follow the seasonal variations of sea temperature. PMID- 26860243 TI - Addiction and eHealth. PMID- 26860244 TI - Commentary on Dowling et al. (2016): Is it time to stop conducting problem gambling prevalence studies? PMID- 26860245 TI - Commentary on Yao et al. (2016): Enforcement uniquely predicts reductions in alcohol-impaired crash fatalities. PMID- 26860246 TI - Commentary on Enns et al. (2016): Supervised injection facilities as a cost effective intervention. PMID- 26860247 TI - Commentary on Binswanger et al. (2016): Multiple opportunities exist to improve the health and wellbeing of people released from prisons. PMID- 26860248 TI - Commentary on Baggio et al. (2016): Internet/gaming addiction is more than heavy use over time. PMID- 26860249 TI - A critique of Fox's industry-funded report into the drivers of anti-social behaviour in the night-time economies of Australia and New Zealand. PMID- 26860250 TI - Drug testing, accuracy and harm reduction: a response to Barratt & Ezard. PMID- 26860251 TI - Ganglioside GD1a promotes oocyte maturation, furthers preimplantation development, and increases blastocyst quality in pigs. AB - Gangliosides are key lipid molecules required for the regulation of cellular processes such as proliferation, differentiation, and cell signaling, including signaling of epidermal growth factor receptor (EGFR). Epidermal growth factor (EGF) has long been considered a potential regulator of meiotic and cytoplasmic maturation in mammalian oocytes. However, there is no report on the direct effect of ganglioside GD1a in porcine oocyte maturation. In this study, we first investigated a functional link between GD1a and meiotic maturation during in vitro maturation (IVM) of porcine embryos. Moreover, we confirmed the effect of exogenous GD1a treatment on blastocyst development, quality, and fertilization rate in early embryonic development. First, we observed that the protein level of ST3GAL2, a GD1a synthesizing enzyme, significantly increased (P < 0.01) in cumulus-oocyte-complexes (COCs) during IVM progress. The proportion of arrested germinal vesicles (GV) increased in oocytes treated with EGF+GD1a (41.6 +/- 1.5%) at the IVM I stage. Upon completion of meiotic maturation, the proportion of metaphase II (M II) was significantly higher (P < 0.05) in the EGF+GD1a (89.9 +/- 3.6%) treated group. After IVF, the percentage of penetrated oocytes was significantly higher (P < 0.05) in the EGF+GD1a (89.1 +/- 2.3%) treated group than in the control group. Furthermore, exogenous GD1a treatment improved the developmental competence and quality of blastocysts during preimplantation embryo development stage. These results suggest that ganglioside GD1a may play an important role in IVM mechanisms of porcine maturation capacity. Furthermore, our findings will be helpful for better promoting the embryo development and blastocyst quality in pigs. PMID- 26860252 TI - Transient ST-segment elevation in precordial leads by acute marginal branch occlusion during stent implantation. AB - The isolated right ventricular infarction is a rare entity. Our case presented a selective occlusion of an acute marginal branch that supplies the right ventricular free wall with isolated ST elevation in precordial leads simulating an occlusion of the left anterior descending artery and without pseudonormalization in inferior due to the non-involvement of the main branch in the ischemic process. Our case clearly illustrates a rare differential diagnosis when a new ST segment elevation appears in earlier precordial leads in patients with symptoms of myocardial ischemia. PMID- 26860253 TI - Response to 'Re: Clinical Relevance of Cardiac Troponin Assessment in Patients Undergoing Carotid Endarterectomy'. PMID- 26860254 TI - Selective Intra-procedural AAA sac Embolization During EVAR Reduces the Rate of Type II Endoleak. AB - OBJECTIVE: The pre-treatment presence of at least six efferent patent vessels (EPV) from the AAA sac and/or AAA thrombus volume ratio (VR%) <40% are considered to be positive predictive factors for persistent type II endoleak (ELIIp). The aim of the present study was to evaluate the effectiveness of sac embolization during EVAR in patients with pre-operative morphological risk factors (p-MRF) for ELIIp. METHODS: Patients undergoing EVAR and intra-procedural AAA sac embolization (Group A, 2012-2013) were retrospectively selected and compared with a control group of patients with the same p-MRF, who underwent EVAR without intra procedural sac embolization (Group B, 2008-2010). The presence of ELIIp was evaluated by duplex ultrasound at 0 and 6 months, and by contrast enhanced ultrasound at 12 months. The association between AAA diameter, age, COPD, smoking, anticoagulant therapy, and AAA sac embolization with ELIIp was evaluated using multiple logistic regression. The primary endpoint was the effectiveness of the intra-procedural AAA sac embolization for ELIIp prevention. Secondary endpoints were AAA sac evolution and freedom from ELIIp and embolization related re-interventions at 6-12 months. RESULTS: Seventy patients were analyzed: 26 Group A and 44 Group B; the groups were homogeneous for clinical/morphological characteristics. In Group A the median number of coils positioned in AAA sac was 4.1 (IQR 1). There were no complications related to the embolization procedures. A significantly lower number of ELIIp was detected in Group A than in Group B (8/26 vs. 33/44, respectively, p < .001) at discharge, and this was confirmed at 6-12 months (7/26 vs. 30/44 respectively, p = .001, and 5/25 vs. 32/44, respectively, p < .001). On multivariate analysis, intra-procedural AAA sac embolization was the only factor independently associated with freedom from ELIIp at 6 (OR 0.196, 95% CI 0.06-0.63; p = .007) and 12 months (OR 0.098, 95% CI 0.02 0.35; p < .001). No differences in median AAA sac diameter shrinkage were detected between the two groups at 6-12 months (p = .42 and p = .58, respectively). Freedom from ELIIp related and embolization related re interventions was 100% in both groups, at 6 and 12 months. CONCLUSION: Selective intra-procedural AAA sac embolization in patients with p-MRF is safe and could be an effective method to reduce ELIIp. Further studies are mandatory to support these results at long-term follow up. PMID- 26860255 TI - Fenestrated Endovascular Aortic Aneurysm Repair as a First Line Treatment Option to Treat Short Necked, Juxtarenal, and Suprarenal Aneurysms. AB - OBJECTIVES: The outcomes of fenestrated endovascular aneurysm repair (FEVAR) as a first line strategy is reported. METHODS: All consecutive patients treated with FEVAR for short neck, juxtarenal, or suprarenal aortic aneurysms under the guidance of the senior author within the period January 2010 to December 2014 were included. Data were collected from a prospectively maintained database. Analyzed outcomes included technical success, defined by successful stent graft implantation with patent stented target vessels and no Type I/III endoleak, operative mortality and morbidity, target vessel patency, endoleak, re intervention, and death. Survival, target vessel stent patency, and re intervention during follow up were calculated by Kaplan-Meier analysis. RESULTS: A total of 281 patients (245 male, mean age 72.1 +/- 7.7 years) were treated. The mean aneurysm diameter was 60.2 +/- 9.3 mm and median proximal neck length 2 mm (range 0-10 mm). Technical success was 96.8% (272/281). Technical failure included one intra-operative death due to embolization and cardiac arrest, one open conversion due to iliac rupture, and seven target vessel complications. The thirty day mortality was 0.7% (2/281). Mean follow up was 21 +/- 15.9 months. Estimated survival at 1 and 3 years was 94.7% +/- 1.6% and 84.6% +/- 3.0%, respectively. Estimated freedom from re-intervention at 1 and 3 years was 96.1% +/- 1.4%, and 90% +/- 2.7%. Estimated target vessel stent patency at 1 and 3 years was 98.6% +/- 0.5%, and 98.1% +/- 0.6%, respectively. Mean aneurysm sac diameter decreased from 60.2 +/- 9.3 mm pre-operatively to 53.2 +/- 12.8 mm (p < .001). CONCLUSIONS: FEVAR as a first line strategy was associated with high technical success and a low operative mortality rate. Efficacy and durability in the mid-term appear very good, with significant regression of aneurysm sac diameter, high target vessel patency, and acceptable rate of re-intervention. PMID- 26860256 TI - Morphological Differences in the Aorto-iliac Segment in AAA Patients of Caucasian and Asian Origin. AB - OBJECTIVE: The objective was to quantify aorto-iliac morphology differences between AAA patients of Caucasian and Asian origin. Additionally, the impact of patient demographic characteristics was assessed, which could influence the morphological differences. METHODS: This international multicentre study included two tertiary referral institutions from Europe and one from China. CT scans with 3D reconstruction of 296 patients with infrarenal AAA >5 cm were analysed. Eighteen measurements were recorded from each CT scan and compared between Caucasian and Asian patients. RESULTS: Caucasian patients had longer common iliac arteries (right: 65.0 vs. 33.1 mm, p < .001 left: 65.0 vs. 35.2 mm, p < .001), longer aneurysm neck (33.0 vs. 28.4 mm, p < .001), greater aneurysm to aortic axis angle (153.0 degrees vs. 142.2 degrees , p < .001), and longer combined aorto-iliac length (195.7 vs. 189.2 mm, p < .001). However, Asian patients had a longer infrarenal abdominal aorta (152.0 vs. 130.0 mm, p < .001), longer AAA (126.2 vs. 93.0 mm), and greater linear distance from renal artery to aorto-iliac bifurcation (143.6 vs. 116.0 mm, p < .001). Caucasian patients had a larger inner common iliac artery diameter (right: 16.0 vs. 14.9 mm, p < .001, left: 16.0 vs. 15.2 mm, p < .001), larger inner exernal iliac artery diameter (right: 9.0 vs. 7.5 mm, p < .001 left: 9.0 vs. 7.7 mm, p < .001), and larger inner common femoral artery diameter (right: 10.0 vs. 5.9 mm, p < .001 left: 10.0 vs. 6.1 mm, p < .001). No difference was observed in AAA transverse diameter (62.0 vs. 63.1 mm, p = .492). CONCLUSION: The results showed that aorto-iliac anatomy in Caucasians differs significantly from Asians, particularly in the length of the common iliac arteries and infrarenal abdominal aorta, and in the transverse diameter of the common, external iliac, and common femoral arteries. Therefore, the exact criteria for stent graft design are dependent on the racial origin of the patient. PMID- 26860257 TI - Re: 'Management of Chronic Venous Disease. Clinical Practice Guidelines of the European Society for Vascular Surgery'. PMID- 26860258 TI - Human Campylobacteriosis in Luxembourg, 2010-2013: A Case-Control Study Combined with Multilocus Sequence Typing for Source Attribution and Risk Factor Analysis. AB - Campylobacteriosis has increased markedly in Luxembourg during recent years. We sought to determine which Campylobacter genotypes infect humans, where they may originate from, and how they may infect humans. Multilocus sequence typing was performed on 1153 Campylobacter jejuni and 136 C. coli human strains to be attributed to three putative animal reservoirs (poultry, ruminants, pigs) and to environmental water using the asymmetric island model. A nationwide case-control study (2010-2013) for domestic campylobacteriosis was also conducted, including 367 C. jejuni and 48 C. coli cases, and 624 controls. Risk factors were investigated by Campylobacter species, and for strains attributed to different sources using a combined case-control and source attribution analysis. 282 sequence types (STs) were identified: ST-21, ST-48, ST-572, ST-50 and ST-257 were prevailing. Most cases were attributed to poultry (61.2%) and ruminants (33.3%). Consuming chicken outside the home was the dominant risk factor for both Campylobacter species. Newly identified risk factors included contact with garden soil for either species, and consuming beef specifically for C. coli. Poultry associated campylobacteriosis was linked to poultry consumption in wintertime, and ruminant-associated campylobacteriosis to tap-water provider type. Besides confirming chicken as campylobacteriosis primary source, additional evidence was found for other reservoirs and transmission routes. PMID- 26860260 TI - Automatic graphene transfer system for improved material quality and efficiency. AB - In most applications based on chemical vapor deposition (CVD) graphene, the transfer from the growth to the target substrate is a critical step for the final device performance. Manual procedures are time consuming and depend on handling skills, whereas existing automatic roll-to-roll methods work well for flexible substrates but tend to induce mechanical damage in rigid ones. A new system that automatically transfers CVD graphene to an arbitrary target substrate has been developed. The process is based on the all-fluidic manipulation of the graphene to avoid mechanical damage, strain and contamination, and on the combination of capillary action and electrostatic repulsion between the graphene and its container to ensure a centered sample on top of the target substrate. The improved carrier mobility and yield of the automatically transferred graphene, as compared to that manually transferred, is demonstrated by the optical and electrical characterization of field-effect transistors fabricated on both materials. In particular, 70% higher mobility values, with a 30% decrease in the unintentional doping and a 10% strain reduction are achieved. The system has been developed for lab-scale transfer and proved to be scalable for industrial applications. PMID- 26860259 TI - Quorum sensing activity of Citrobacter amalonaticus L8A, a bacterium isolated from dental plaque. AB - Cell-cell communication is also known as quorum sensing (QS) that happens in the bacterial cells with the aim to regulate their genes expression in response to increased cell density. In this study, a bacterium (L8A) isolated from dental plaque biofilm was identified as Citrobacter amalonaticus by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Its N-acylhomoserine-lactone (AHL) production was screened by using two types of AHL biosensors namely Chromobacterium violaceum CV026 and Escherichia coli [pSB401]. Citrobacter amalonaticus strain L8A was identified and confirmed producing numerous types of AHL namely N-butyryl-L-homoserine lactone (C4-HSL), N hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL) and N-hexadecanoyl-L-homoserine lactone (C16-HSL). We performed the whole genome sequence analysis of this oral isolate where its genome sequence reveals the presence of QS signal synthase gene and our work will pave the ways to study the function of the related QS genes in this bacterium. PMID- 26860263 TI - Modelling and extraction of variability in free-text medication prescriptions from an anonymised primary care electronic medical record research database. AB - BACKGROUND: Free-text medication prescriptions contain detailed instruction information that is key when preparing drug data for analysis. The objective of this study was to develop a novel model and automated text-mining method to extract detailed structured medication information from free-text prescriptions and explore their variability (e.g. optional dosages) in primary care research databases. METHODS: We introduce a prescription model that provides minimum and maximum values for dose number, frequency and interval, allowing modelling variability and flexibility within a drug prescription. We developed a text mining system that relies on rules to extract such structured information from prescription free-text dosage instructions. The system was applied to medication prescriptions from an anonymised primary care electronic record database (Clinical Practice Research Datalink, CPRD). RESULTS: We have evaluated our approach on a test set of 220 CPRD prescription free-text directions. The system achieved an overall accuracy of 91 % at the prescription level, with 97 % accuracy across the attribute levels. We then further analysed over 56,000 most common free text prescriptions from CPRD records and found that 1 in 4 has inherent variability, i.e. a choice in taking medication specified by different minimum and maximum doses, duration or frequency. CONCLUSIONS: Our approach provides an accurate, automated way of coding prescription free text information, including information about flexibility and variability within a prescription. The method allows the researcher to decide how best to prepare the prescription data for drug efficacy and safety analyses in any given setting, and test various scenarios and their impact. PMID- 26860262 TI - Diet-related greenhouse gas emissions assessed by a food frequency questionnaire and validated using 7-day weighed food records. AB - BACKGROUND: The current food system generates about 25 % of total greenhouse gas emissions (GHGE), including deforestation, and thereby substantially contributes to the warming of the earth's surface. To understand the association between food and nutrient intake and GHGE, we therefore need valid methods to assess diet related GHGE in observational studies. METHODS: Life cycle assessment (LCA) studies assess the environmental impact of different food items. We linked LCA data expressed as kg carbon dioxide equivalents (CO2e) per kg food product to data on food intake assessed by the food frequency questionnaire (FFQ) Meal-Q and validated it against a 7-day weighed food record (WFR). 166 male and female volunteers aged 20-63 years completed Meal-Q and the WFR, and their food intake was linked to LCA data. RESULTS: The mean GHGE assessed with Meal-Q was 3.76 kg CO2e per day and person, whereas it was 5.04 kg CO2e using the WFR. The energy adjusted and deattenuated Pearson and Spearman correlation coefficients were 0.68 and 0.70, respectively. Moreover, compared to the WFR, Meal-Q provided a good ranking ability, with 90 % of the participants classified into the same or adjacent quartile according to their daily average CO2e. The Bland-Altman plot showed an acceptable level of agreement between the two methods and the reproducibility of Meal-Q was high. CONCLUSIONS: This is the first study validating the assessment of diet-related GHGE by a questionnaire. The results suggest that Meal-Q is a useful tool for studying the link between food habits and CO2e in future epidemiological studies. PMID- 26860261 TI - Paediatric obstructive sleep apnoea syndrome (OSAS) is associated with tonsil colonisation by Streptococcus pyogenes. AB - The involvement of pathogenic bacteria in obstructive sleep apnoea syndrome (OSAS) has yet to be elucidated. We investigated the possible role of group A streptococcus (GAS) in OSAS pathogenesis. In 40 tonsillectomized patients affected by OSAS and 80 healthy controls, significant (p < 0.0001) association of GAS with paediatric OSAS was found. Supernatant from streptolysin O (SLO) producing GAS induced production of cysteinyl leukotrienes (CysLTs) in tonsil mononuclear cells (TMCs). CysLTs-treated TMCs showed significant (p < 0.05) proliferation of CD4+ T, CD19+ and CD19+CD27+CD38+ B lymphocytes. We discovered a SLO-dependent activation of CysLTs production through a pathway involving TOLL like receptor 4 (TLR4), TIR-domain-containing adapter-inducing interferon-beta (TRIF), Myeloid differentiation primary response gene 88 (MyD88), and p38 MAP Kinase. In conclusion, we hypothesise that GAS may contribute to paediatric tonsillar hyperplasia through CysLTs production induced by SLO, and this might explain its association with OSAS. PMID- 26860264 TI - Inflammatory biomarker score and cancer: A population-based prospective cohort study. AB - BACKGROUND: Inflammation is associated with cancer but there are conflicting reports on associations of biomarkers of inflammation with cancer risk and mortality. We investigated the associations of C-reactive protein (CRP) and leukocyte count with cancer risk and mortality using individual biomarkers, and an inflammatory score derived from both biomarkers. METHODS: We conducted this analysis among 2,570 men enrolled in the population-based, prospective Kuopio Ischemic Heart Disease Risk Factor Study in Finland. During an average follow-up period of 26 years, 653 cancer cases and 287 cancer deaths occurred. We computed a z-score for each participant, with the combined z-score being the sum of each individual's CRP and leukocyte z-scores. Multivariable-adjusted Cox proportional hazard model was used to evaluate associations with cancer risk and mortality. RESULTS: Using individual biomarkers, elevated leukocyte count was associated with an increased risk of cancer (RR = 1.31, 95% CI 1.04-1.66), and cancer mortality (RR=, 95% CI 1.39, 0.98-1.97). The corresponding results for CRP were (RR = 1.23, 95% CI 0.97-1.55) for risk and (RR = 1.15, 95% CI 0.81-1.64) for cancer mortality. Associations of the biomarkers with cancer appeared to be more robust using the combined z-score. HRs comparing men within the highest z-score quartile to those within the lowest z-score quartiles were 1.47 (95% CI 1.16 1.88, p-trend < 0.01) for cancer risk, and 1.48 (95% CI 1.03-2.14, p-trend = 0.09) for cancer mortality. CONCLUSION: Our study suggests that inflammation is associated with cancer risk and mortality, and combining inflammatory biomarkers into a score is a robust method of elucidating this association. PMID- 26860265 TI - The resilience of forest fragmentation genetics-no longer a paradox-we were just looking in the wrong place. PMID- 26860267 TI - Gut microbiota: Microbes offer engineering strategies to combat cancer. PMID- 26860268 TI - NASH: NASH and TLR9. PMID- 26860266 TI - Breakthroughs in the treatment and prevention of Clostridium difficile infection. AB - This Review summarizes the latest advances in the treatment and prevention of Clostridium difficile infection (CDI), which is now the most common health-care associated infection in the USA. As traditional, standard CDI antibiotic therapies (metronidazole and vancomycin) are limited by their broad spectrum and further perturbation of the intestinal microbiota, which result in unacceptably high recurrence rates, novel therapeutic strategies for CDI are needed. Emerging CDI therapies are focused on limiting further perturbation of the intestinal microbiota and/or restoring the microbiota to its pre-morbid state, reducing colonization of the intestinal tract by toxigenic strains of C. difficile and bolstering the host immune response against C. difficile toxins. Fidaxomicin is associated with reduced CDI recurrences, and other emerging narrow-spectrum CDI antibiotic therapies might eventually demonstrate a similar benefit. Prevention of intestinal colonization of toxigenic strains of C. difficile can be achieved through restoration of the intestinal microbiota with faecal microbiota transplantation, as well as by colonizing the gut with nontoxigenic C. difficile strains. Finally, emerging immunological therapies, including monoclonal antibodies and vaccines against C. difficile toxins, might protect against CDI and subsequent CDI recurrences. The available clinical data for these emerging therapies, and their relative advantages and disadvantages, are described. PMID- 26860269 TI - Liver: DNA methylation controls liver fibrogenesis. PMID- 26860270 TI - Hepatocellular carcinoma: A role for lncRNA in liver cancer. PMID- 26860271 TI - Taxonomic status and molecular phylogeography of two sibling species of Polytremis (Lepidoptera: Hesperiidae). AB - The skipper Polytremis theca species complex is widely distributed in the south of the Qinling Mountains in China. A recent study of the Polytremis genus suggested that this species might encompass two differentiated lineages. We tested this hypothesis, by carrying out a phylogenetic study of this agricultural pest based on nationwide sampling and the evaluation of mitochondrial and nuclear DNA markers. We show that this species is actually an amalgamation of two sibling taxa (P. t. theca and P. t. fukia), which displayed levels of genetic divergence as great as those generally found between sister species in the Polytremis genus, suggesting that they actually correspond to two distinct species. The Divergence time estimates suggest that an active period of speciation within Polytremis occurred within the Pleistocene eras. Based on its distinct phylogenetic placement and geographical isolation, we suggest that the subspecies should be elevated to full species status under the phylogenetic species concept, which has significant management implications. PMID- 26860273 TI - A new minimally invasive technique of combined chest wall resection for lung cancer. AB - We describe our technique of minimally invasive chest wall resection for primary lung cancer. We used this technique to perform two lobectomies combined with chest wall resection using thoracoscopic assistance. The intercostal muscles and vessels were divided using a vessel-sealing device, which was easy to maneuver through the access incision, achieving reliable hemostasis. In one patient, adding the utility port just over the dorsal edge of the chest wall proved useful for dissecting the distal area of the chest wall. This approach required only minimal incision without cutting the uninvolved extrathoracic musculature of the chest. PMID- 26860275 TI - Letter to the editor. PMID- 26860274 TI - Concurrent gemcitabine+S-1 neoadjuvant chemotherapy contributes to the improved survival of patients with small borderline-resectable pancreatic cancer tumors. AB - PURPOSES: In the surgical treatment of pancreatic cancer, margin-negative status is one of the most important determinants of survival. We conducted this study to explore surgical margin status as well as other factors affecting the survival of borderline-resectable pancreatic cancer (BRPC) patients who received neoadjuvant chemotherapy with gemcitabine and S-1. METHODS: Eighteen BRPC patients were prospectively treated with concurrent gemcitabine and S-1 neoadjuvant chemotherapy (NAC+) and 15 of these patients underwent resection. We evaluated the safety and efficacy of this treatment regimen by comparing the outcomes of these patients with those of 19 BRPC patients who did not receive neoadjuvant chemotherapy (NAC-) during the same period. RESULTS: Fifteen (83 %) of the NAC+ patients underwent pancreatectomy. The remaining three patients (17 %) had regional tumor progression or liver metastasis. Of the 15 NAC+ patients who underwent resection, 3 (20 %) had margin-positive status, whereas 9 of the 19 (43 %) NAC- patients had margin-positive status (p = 0.002). However, disease-free survival and overall survival were similar in the two groups (MST 21.7 vs. 21.1 months). NAC+ patients with tumors smaller than 30 mm had favorable overall survival (MST 43.9 vs. 23.1 months, p = 0.0321). Most recurrences developed at distant sites rather than locally in both groups. CONCLUSIONS: In the neoadjuvant setting, gemcitabine and S-1 improved the negative surgical margin rate in BRPC patients, but it did not improve survival. Thus, neoadjuvant chemotherapy should be given to BRPC patients at an earlier stage. PMID- 26860276 TI - Implementation Measurement for Evidence-Based Violence Prevention Programs in Communities. AB - Increasing attention to the evaluation, dissemination, and implementation of evidence-based programs (EBPs) has led to significant advancements in the science of community-based violence prevention. One of the prevailing challenges in moving from science to community involves implementing EBPs and strategies with quality. The CDC-funded National Centers of Excellence in Youth Violence Prevention (YVPCs) partner with communities to implement a comprehensive community-based strategy to prevent violence and to evaluate that strategy for impact on community-wide rates of violence. As part of their implementation approach, YVPCs document implementation of and fidelity to the components of the comprehensive youth violence prevention strategy. We describe the strategies and methods used by the six YVPCs to assess implementation and to use implementation data to inform program improvement efforts. The information presented describes the approach and measurement strategies employed by each center and for each program implemented in the partner communities. YVPCs employ both established and innovative strategies for measurement and tracking of implementation across a broad range of programs, practices, and strategies. The work of the YVPCs highlights the need to use data to understand the relationship between implementation of EBPs and youth violence outcomes. PMID- 26860277 TI - Poor HPV vaccine-related awareness and knowledge among Utah Latinas overdue for recommended cancer screenings. AB - Individuals overdue for recommended cancer screenings may not be receiving adequate cancer prevention education. Since Latinas have the highest incidence of cervical cancer among all racial/ethnic groups, human papillomavirus (HPV) vaccination education is especially important for this population. The correlates of HPV vaccine-related awareness and knowledge were assessed among Latinas who were overdue for recommended cancer screenings. N = 206 Latinas who were overdue for recommended cancer screenings were recruited by health educators from local community groups. Bivariate analyses and multivariable regression models were used to investigate factors associated with HPV vaccine-related awareness and knowledge among participants as well as to assess correlates of HPV vaccine receipt for eligible children of participants. In multivariable regression analyses, years living in the U.S. (p = 0.05) and health insurance status (p = 0.03) were significantly related to HPV vaccine-related knowledge measures. Age (p < 0.01), birthplace (p = 0.02), years living in the U.S. (p = 0.05), annual household income (p = 0.05), cervical cancer screening status (p = 0.03), and HPV vaccine-related knowledge measures (p < 0.01) were significantly associated with HPV vaccination outcomes for eligible daughters of participants. Cervical cancer screening status (p = 0.02) and HPV vaccine-related knowledge measures (p = 0.01) were significantly associated with HPV vaccination outcomes for eligible sons of participants. Results indicate poor HPV vaccine-related awareness and knowledge among Latinas. Interventions to improve HPV vaccine-related awareness and knowledge in Utah's growing Latino population should target vulnerable individuals (e.g., not employed outside the home, less educated, less acculturated, poor, uninsured, overdue for cervical cancer screening) by using materials that are culturally sensitive, linguistically appropriate, and easily accessible. PMID- 26860279 TI - Large-scale synthesis of N-doped carbon quantum dots and their phosphorescence properties in a polyurethane matrix. AB - An easy, large-scale synthesis of N-doped carbon quantum dots (CQDs) was developed by using isophorone diisocyanate (IPDI) as a single carbon source under microwave irradiation. The yield of raw N-doped CQDs was about 83%, which is suitable for industrial-scale production. A detailed formation mechanism for N doped CQDs involving self-polymerization and condensation of IPDI was demonstrated. Moreover, the obtained N-doped CQDs can be homogeneously dispersed in various organic monomers and do not need toxic organic solvents as dispersing agents. This advantage expands the range of applications of CQDs in composites. The N-doped CQDs dispersed in polyurethane (PU) matrixes emit not only fluorescence but also phosphorescence and delayed fluorescence at room temperature upon excitation with ultraviolet (UV) light. Furthermore, the phosphorescence of CQD/PU composites is sensitive to oxygen and therefore, the obtained-CQDs could be exploited in the development of novel oxygen sensors. PMID- 26860278 TI - Overcoming Barriers to Eye Care: Patient Response to a Medical Social Worker in a Glaucoma Service. AB - This paper investigates the patient response to a medical social worker in a glaucoma clinic. The literature suggests that medical social workers are effective in a variety of health care settings, yet the efficacy of a medical social worker in an adult ophthalmic setting has not been studied. We present the results of a retrospective chart review of 50 patients with glaucoma referred to a medical social worker between January 5, 2015 and June 31, 2015 in an outpatient clinic of an urban eye hospital. Clinical and demographic data, as well as the data from a quality of care questionnaire, were collected for each patient. Patients rated their interaction with the medical social worker as highly positive (mean = 4.75, 5-point Likert scale), and nearly 90 % of patients expressed interest in future contact with the social worker. Additionally, most patients reported that the social worker resolved the issues they were facing (61.1 %), supported them in seeing their ophthalmologist (70.6 %), and helped them to manage their glaucoma (69.7 %). Reported barriers to glaucoma care were emotional distress; cost of office visits and medications; lack of medical insurance; transportation; poor medication adherence; impairment of daily activities; follow-up adherence; and language. As vision loss from glaucoma is irreversible, it is important to detect and treat patients at early stages of the disease. Therefore, it is imperative for patients to regularly visit their eye care providers and adhere to treatment and follow-up recommendations. This study suggests that a medical social worker could play a pivotal role in helping patients with glaucoma overcome barriers to treatment and facilitate disease management. PMID- 26860280 TI - Household Size and the Decision to Purchase Health Insurance in Cambodia: Results of a Discrete-Choice Experiment with Scale Adjustment. AB - BACKGROUND: Community-based health insurance (CBHI) schemes have been introduced in low- and middle-income countries to increase health service utilization and provide financial protection from high healthcare expenditures. OBJECTIVE: We assess the impact of household size on decisions to enroll in CBHI and demonstrate how to correct for group disparity in scale (i.e. variance differences). METHODS: A discrete choice experiment was conducted across five CBHI attributes. Preferences were elicited through forced-choice paired comparison choice tasks designed based on D-efficiency. Differences in preferences were examined between small (1-4 family members) and large (5-12 members) households using conditional logistic regression. Swait and Louviere test was used to identify and correct for differences in scale. RESULTS: One hundred and sixty households were surveyed in Northwest Cambodia. Increased insurance premium was associated with disutility [odds ratio (OR) 0.61, p < 0.01], while significant increase in utility was noted for higher hospital fee coverage (OR 10.58, p < 0.01), greater coverage of travel and meal costs (OR 4.08, p < 0.01), and more frequent communication with the insurer (OR 1.33, p < 0.01). While the magnitude of preference for hospital fee coverage appeared larger for the large household group (OR 14.15) compared to the small household group (OR 8.58), differences in scale were observed (p < 0.05). After adjusting for scale (k, ratio of scale between large to small household groups = 1.227, 95 % confidence interval 1.002-1.515), preference differences by household size became negligible. CONCLUSION: Differences in stated preferences may be due to scale, or variance differences between groups, rather than true variations in preference. Coverage of hospital fees, travel and meal costs are given significant weight in CBHI enrollment decisions regardless of household size. Understanding how community members make decisions about health insurance can inform low- and middle-income countries' paths towards universal health coverage. PMID- 26860282 TI - A novel combined strategy for the physical PEGylation of polypeptides. AB - Poly(ethylene glycol) (PEG) may be covalently conjugated to peptide drugs to overcome their rapid clearance but in doing so their potency can be lost. Here, a non-covalent approach was used to conjugate PEG bearing a terminal cholanic moiety (mPEG5kDa-cholane) to a 28 amino acid peptide, vasoactive intestinal peptide (VIP). Palmitoylation of the peptide was essential to facilitate physical interaction via a single binding site involving two mPEG5kDa-cholane molecules with an affinity constant of ~3.10(4)M(-1); these calorimetry data corroborating Scatchard analysis of dissolution data. The peptide/polymer complex (below 10 12nm diameter) provided for up to 5000-fold greater solubility of the peptide at pH7.4 (4MUg/mL) and markedly increased peptide solution stability at 25 degrees C over 30days. Mannitol enabled the complex to be lyophilized to yield a freeze dried formulation which was efficiently reconstituted albeit with an ~10% decrease in solubility. The predominantly alpha-helical conformation of the peptide alone at pH5-6.5 was lost at pH7.4 but fully recovered with 2 molar equivalents of mPEG5kDa-cholane. After lyophilization and reconstitution an ~10% loss of alpha-helical conformation was observed, which may reflect the equivalent decrease in solubility. Pharmacokinetic studies following subcutaneous administration of the peptide (0.1mg/Kg) alone and with 2 molar equivalents of polymer showed that mPEG5kDa-cholane dramatically increased peptide concentration in the systemic circulation. This is the first demonstration of non-covalent PEGylation of acylated peptides, an important biologic class, which improves in vitro and in vivo properties, and thereby may prove an alternative to covalent PEGylation strategies. PMID- 26860281 TI - Microbubbles and ultrasound increase intraventricular polyplex gene transfer to the brain. AB - Neurons in the brain can be damaged or lost from neurodegenerative disease, stroke, or traumatic injury. Although neurogenesis occurs in mammalian adult brains, the levels of natural neurogenesis are insufficient to restore function in these cases. Gene therapy has been pursued as a promising strategy to induce differentiation of neural progenitor cells into functional neurons. Non-viral vectors are a preferred method of gene transfer due to potential safety and manufacturing benefits but suffer from lower delivery efficiencies compared to viral vectors. Since the neural stem and progenitor cells reside in the subventricular zone of the brain, intraventricular injection has been used as an administration route for gene transfer to these cells. However, the choroid plexus epithelium remains an obstacle to delivery. Recently, transient disruption of the blood-brain barrier by microbubble-enhanced ultrasound has been used to successfully improve drug delivery to the brain after intravenous injection. In this work, we demonstrate that microbubble-enhanced ultrasound can similarly improve gene transfer to the subventricular zone after intraventricular injection. Microbubbles of different surface charges (neutral, slightly cationic, and cationic) were prepared, characterized by acoustic flow cytometry, and evaluated for their ability to increase the permeability of immortalized choroid plexus epithelium monolayers in vitro. Based on these results, slightly cationic microbubbles were evaluated for microbubble and ultrasound-mediated enhancement of non-viral gene transfer in vivo. When coupled with our previously reported gene delivery vehicles, the slightly cationic microbubbles significantly increased ultrasound-mediated transfection of the murine brain when compared to commercially available Definity(r) microbubbles. Temporary disruption of the choroid plexus by microbubble-enhanced ultrasound is therefore a viable way of enhancing gene delivery to the brain and merits further research. PMID- 26860283 TI - Imaging-guided photoacoustic drug release and synergistic chemo-photoacoustic therapy with paclitaxel-containing nanoparticles. AB - Here, a novel triggered drug release modality was developed for oncotherapy. Paclitaxel (PTX), perfluorohexane (PFH) and gold nanorods (AuNRs) loaded nanoparticles (PTX-PAnP) were synthesized. Folic acid (FA) conjugated PTX-PAnP (PTX-PAnP-FA) could be selectively taken into folate receptor-overexpressed tumor cells. Upon pulsed laser irradiation, the PTX-PAnP-FA could be rapidly destructed because of the PFH vaporization, resulting in fast drug release, which induced apoptosis of cancer cells efficiently. Stimulated fragmentation of the PTX-PAnP FA nanoparticles can facilitate multiple mechanisms such as bubble implosion, shockwave generation, and sonoporation that further enhance the therapeutic efficiency. The in vivo therapy study further confirmed this new approach resulted in efficient tumor suppression. The results demonstrate a unique drug release mechanism based on photoacoustic effect. It provides an all-in-one platform for photoacoustic image-guided drug release and synergistic chemo photoacoustic therapy. PMID- 26860284 TI - Role of antibodies in diagnosis and treatment of ovarian cancer: Basic approach and clinical status. AB - Ovarian cancer is the second most leading gynecological cancer after endometrial cancer in women. Chemotherapy and cyto-reductive surgery are currently the mainstays for treatment of ovarian cancer in early stages. However, the overall 5years of survival rate in advanced stage is just 20-30%. The main reasons behind therapeutic failures and a low survival rate are challenges in early diagnosis, frequent recurrence, chemo-resistance development and lack of targeting. Antibodies have evolved as a rationale therapeutic approach to overcome these hurdles and to engender significant clinical applications. Detection of cancer associated antibodies and radiolabeled antibody conjugates are forming the basis for early diagnosis of ovarian cancer. Besides this, antibodies when given alone act as an anti-angiogenic agent or utilize the protective role of immune system against ovarian cancer. This high specificity and selectivity of action is also accompanied by development of tumor antigen-specific memory T cells, which can prevent cancer recurrence. In addition, when given in combination with chemotherapy, antibodies have turned out to sensitize chemo-resistant tumors. Antibodies are also playing cardinal role in design of highly potent class of targeted therapies, such as antibody-drug conjugates and clinically viable tumor targeted drug nanocarriers. This article aims to explore the fundamentals in development of antibody based therapeutics and multitude ways of clinical applications in diagnosis and treatment of ovarian cancer. Focus is given on the recent advances made in preclinical and clinical settings with an overview to unmet challenges so as to develop better immunotherapeutics in future. PMID- 26860285 TI - In vitro and in vivo evaluation of novel implantation technology in hydrogel contact lenses for controlled drug delivery. AB - Glaucoma is commonly treated using eye drops, which is highly inefficient due to rapid clearance (low residence time) from ocular surface. Contact lenses are ideally suited for controlled drug delivery to cornea, but incorporation of any drug loaded particulate system (formulation) affect the optical and physical property of contact lenses. The objective of the present work was to implant timolol maleate (TM) loaded ethyl cellulose nanoparticle-laden ring in hydrogel contact lenses that could provide controlled drug delivery at therapeutic rates without compromising critical lens properties. TM-implant lenses were developed, by dispersing TM encapsulated ethyl cellulose nanoparticles in acrylate hydrogel (fabricated as ring implant) and implanted the same in hydrogel contact lenses (sandwich system). The TM-ethyl cellulose nanoparticles were prepared by double emulsion method at different ratios of TM to ethyl cellulose. The X-ray diffraction studies revealed the transformation of TM to amorphous state. In vitro release kinetic data showed sustained drug release within the therapeutic window for 168h (NP 1:3 batch) with 150MUg loading. Cytotoxicity and ocular irritation study demonstrated the safety of TM-implant contact lenses. In vivo pharmacokinetic studies in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC), with TM-implant contact lenses in comparison to eye drop therapy. In vivo pharmacodynamic data in rabbit model showed sustained reduction in intra ocular pressure for 192h. The study demonstrated the promising potential of implantation technology to treat glaucoma using contact lenses, and could serve as a platform for other ocular diseases. PMID- 26860286 TI - Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear. AB - The inner ear is one of the most challenging organs for drug delivery, mainly because of the blood-perilymph barrier. Therefore, local rather than systemic drug delivery methods are being developed for inner ear therapy. In this work, we have evaluated the benefit of a hyaluronic acid liposomal gel for sustained delivery of a corticoid to the inner ear after local injection into the middle ear in a guinea pig model. The liposomal gel was easily injectable as a result of the shear-thinning behavior of hyaluronic acid. A prolonged residence time at the site of injection as well as in the round window were achieved without any negative effect on the hearing thresholds of the animals. The presence of liposomes in the formulation resulted in sustained release of the drug in the perilymph for 30days and promoted the conversion of the prodrug loaded within the liposomes (dexamethasone phosphate) into its active form (dexamethasone). In this way, therapeutic doses were attained in the perilymph. A small amount of intact liposomes was visualized in the perilymph, whereas the main proportion of liposomes seemed to be trapped in the round window resulting in a reservoir effect. Thus, the administration of hyaluronic acid liposomal gel to the middle ear is an efficient strategy for delivering corticoids to the inner ear in a sustained manner. PMID- 26860288 TI - Nonsolvent-assisted fabrication of multi-scaled polylactide as superhydrophobic surfaces. AB - The solution-processing fabrication of superhydrophobic surfaces is currently intriguing, owing to high-efficiency, low cost, and energy-consuming. Here, a facile nonsolvent-assisted process was proposed for the fabrication of the multi scaled surface roughness in polylactide (PLA) films, thereby resulting in a significant transformation in the surface wettability from intrinsic hydrophilicity to superhydrophobicity. Moreover, it was found that the surface topographical structure of PLA films can be manipulated by varying the compositions of the PLA solutions. And the samples showed superhydrophobic surfaces as well as high melting enthalpy and crystallinity. In particular, a high contact angle of 155.8 degrees together with a high adhesive force of 184 MUN was yielded with the assistance of a multi-nonsolvent system, which contributed to the co-existence of micro-/nano-scale hierarchical structures. PMID- 26860289 TI - Anatomical "C"-shaped double-bundle versus single-bundle anterior cruciate ligament reconstruction in pre-adolescent children with open growth plates. AB - PURPOSE: To analyse the clinical, rotational and radiological (MRI) results of paediatric anatomical "C-shaped" double-bundle (DB) anterior cruciate ligament (ACL) reconstruction with anteromedial and posteromedial bundle compared to single-bundle (SB) ACL reconstruction. METHODS: Between 2008 and 2014, 57 consecutive patients received a paediatric ACL reconstruction with open physis and were allocated into two groups, according to the surgical procedure. Transepiphyseal SB technique was used until 2012 and DB consecutively thereafter. Follow-up consisted of a clinical evaluation with assessment of the International Knee Documentation Committee (IKDC) form, the Lysholm knee score, Tegner activity score, KT-1000 arthrometer evaluation, VAS Scores for satisfaction, MRI and testing of rotational stability using a robotic system. RESULTS: The mean time from ACL reconstruction to follow-up was 48.1 +/- 15.8 in the SB group (n = 17) and 23.1 +/- 13.2 in the DB group (n = 16; p < 0.001). No differences were found in the subjective scores. Biomechanically, there were significant differences identified in the KT-1000 (p < 0.03) and total tibial axial rotation (p < 0.04) when evaluating the reconstructed knee only. Ten of 17 (59%) of the SB patients had a Joint Play Area within the acceptable range of the median healthy knee value compared to 100 % in the DB group. Decreased patient satisfaction was associated with increased total tibial axial rotation. No growth disturbance was observed. Overall, 98% of patients were reached and either examined or interviewed. Re-rupture rate was 3 of 21 (14.3%) for DB and 9 of 35 (25.7%) for SB. All but one re-ruptures (92%) happened in the first 16 postoperative months independent of technique. CONCLUSIONS: The re-rupture rate after pre-adolescent ACL reconstruction is too high both historically and in this mixed cohort. Anatomical transepiphyseal DB ACL reconstruction with open physis may result in a reduction in this re-rupture rate, which may be related to a tighter control of the Joint Play Area. While subjective clinical results were similar between SB and DB, decreased patient satisfaction was associated with increased total tibial axial rotation in the entire cohort. Despite the need for two transepiphyseal tunnels in the DB technique, there did not appear to be an increased risk in growth plate disturbance. Transepiphyseal DB ACL reconstruction appears to be a reasonable alternative to current techniques in pre-adolescent children with an ACL rupture. LEVEL OF EVIDENCE: IV. PMID- 26860290 TI - Intraarticular hamstring graft diameter decreases with continuing knee growth after ACL reconstruction with open physes. AB - PURPOSE: To evaluate the graft diameter size after one-year follow-up or more of patients Tanner II, III, and IV who were submitted to anterior cruciate ligament reconstruction. METHODS: Ten patients [five males (mean age: 14.4 years) and five females (mean age: 13.6 years)] with open physis and anterior cruciate ligament tear were submitted to transphyseal anterior cruciate ligament reconstruction with quadruple hamstrings graft. During the procedure, graft and tunnel size were recorded. After last clinical follow-up (range 1-11 years), an MRI study was requested and their measurements near the tibial tunnel were compared with the graft diameter measured and used during primary procedure. RESULTS: Four patients had Tanner stage II, four patients Tanner stage III, and two Tanner IV. There were statistically significant decreases in the quadruple hamstrings graft diameter size (average of 25.3%). Mean size at time of surgery was 7.9 mm (+/ 0.87), and mean size measured at different points of follow-up evaluation was 5.9 mm (+/-0.65). CONCLUSION: Diameter size of hamstring graft in skeletally immature patients is smaller in most cases. If there is a decrease in the diameter of the graft along postoperative time, the risk of a re-rupture is theoretically further increased. Quadruple hamstring graft decreases a mean 25.3% in diameter from time of anterior cruciate ligament reconstruction surgery until reassessment period in skeletally immature patients. LEVEL OF EVIDENCE: IV. PMID- 26860291 TI - Was it worth it? Patients' perspectives on the perceived value of genomic-based individualized medicine. AB - The value of genomic sequencing is often understood in terms of its ability to affect diagnosis or treatment. In these terms, successes occur only in a minority of cases. This paper presents views from patients who had exome sequencing done clinically to explore how they perceive the utility of genomic medicine. The authors used semi-structured, qualitative interviews in order to study patients' attitudes toward genomic sequencing in oncology and rare-disease settings. Participants from 37 cases were interviewed. In terms of the testing's key values regardless of having received what clinicians described as meaningful results participants expressed four qualities that are separate from traditional views of clinical utility: Participants felt they had been empowered over their own health. They felt they had contributed altruistically to the progress of genomic technology in medicine. They felt their suffering had been legitimated. They also felt a sense of closure, having done everything they could. Patients expressed overwhelmingly positive attitudes toward sequencing. Their rationale was not solely based on the results' clinical utility. It is important for clinicians to understand this non-medical reasoning as it pertains to patient decision-making and informed consent. PMID- 26860287 TI - Mucosal vaccine delivery: Current state and a pediatric perspective. AB - Most childhood infections occur via the mucosal surfaces, however, parenterally delivered vaccines are unable to induce protective immunity at these surfaces. In contrast, delivery of vaccines via the mucosal routes can allow antigens to interact with the mucosa-associated lymphoid tissue (MALT) to induce both mucosal and systemic immunity. The induced mucosal immunity can neutralize the pathogen on the mucosal surface before it can cause infection. In addition to reinforcing the defense at mucosal surfaces, mucosal vaccination is also expected to be needle-free, which can eliminate pain and the fear of vaccination. Thus, mucosal vaccination is highly appealing, especially for the pediatric population. However, vaccine delivery across mucosal surfaces is challenging because of the different barriers that naturally exist at the various mucosal surfaces to keep the pathogens out. There have been significant developments in delivery systems for mucosal vaccination. In this review we provide an introduction to the MALT, highlight barriers to vaccine delivery at different mucosal surfaces, discuss different approaches that have been investigated for vaccine delivery across mucosal surfaces, and conclude with an assessment of perspectives for mucosal vaccination in the context of the pediatric population. PMID- 26860293 TI - Development of TASP0410457 (TASP457), a novel dihydroquinolinone derivative as a PET radioligand for central histamine H3 receptors. AB - BACKGROUND: Histamine H3 receptor (H3R) is a potential therapeutic target of sleep- and cognition-related disorders. The purpose of the present study is to develop a novel positron emission tomography (PET) ligand for H3Rs from dihydroquinolinone derivatives, which we previously found to have high affinity with these receptors. METHODS: Six compounds were selected from a dihydroquinolinone compound library based on structural capability for (11)C labeling and binding affinity for H3Rs. Their in vivo kinetics in the rat brain were examined in a comparative manner by liquid chromatography and tandem mass spectrometry (LC-MS/MS). Chemicals with appropriate kinetic properties were then labeled with (11)C and evaluated in rats and monkeys using PET. RESULTS: Of the six compounds, TASP0410457 (also diminutively called TASP457) and TASP0434988 exhibited fast kinetics and relatively high brain uptakes in ex vivo LC-MS/MS and were selected as candidate PET imaging agents. PET data in rat brains were mostly consistent with LC-MS/MS findings, and rat and monkey PET scans demonstrated that [(11)C]TASP0410457 was superior to [(11)C]TASP0434988 for high-contrast H3R PET imaging. In the monkey brain PET, distribution volume for [(11)C]TASP0410457 could be quantified, and receptor occupancy by a nonradioactive compound was measurable using this radioligand. The specific binding of [(11)C]TASP0410457 to H3Rs was confirmed by autoradiography using rat and monkey brain sections. CONCLUSIONS: We developed [(11)C]TASP0410457 as a radioligand enabling a robust quantification of H3Rs in all brain regions and demonstrated the utility of ex vivo LC-MS/MS and in vivo PET assays for selecting appropriate imaging tracers. [(11)C]TASP0410457 will help to examine the implication of H3Rs in neuropsychiatric disorders and to characterize emerging therapeutic agents targeting H3Rs. PMID- 26860294 TI - Radiolabeling polymeric micelles for in vivo evaluation: a novel, fast, and facile method. AB - BACKGROUND: Single photon emission computed tomography (SPECT) is an indispensable tool in the determination of the in vivo fate of polymeric micelles. However, for this purpose, the micelles need to be radiolabeled, and almost all radiolabeling procedures published to date involve the conjugation of a chelating agent to the constituting polymer, which could actually affect their biodistribution. In this paper, we report a new facile method for radiolabeling polystyrene-b-poly(ethylene oxide) diblock copolymer micelles without the necessity of any chemical modification. Instead, we entrap the radiolabel (i.e., (111)In) in the micellar core during the formation of the micelles by using tropolone as lipophilic ligand. METHODS: Micelles were prepared by emulsifying a polymer solution in chloroform with a buffer containing (111)In and lipophilic ligand tropolone, by stirring for about 2 h. The produced micelles were physically characterized by means of dynamic light scattering and transmission electron microscopy. The biological properties of the radiolabeled micelles were determined by means of in vivo and ex vivo evaluation. SPECT analysis was done on Balb/c-nu mice, after administration of 1 mg micelles containing 22 MBq of (111)In. SPECT images were obtained over 24 h. Biodistribution of the micelles was assessed also ex vivo. RESULTS: The radiolabeling method is robust and reproducible with constant radiolabeling efficiency (~30 %) even at indium concentrations that are much higher than the necessary for in vivo studies, and the radiolabel retention is more than 80 % in mouse serum at 48 h. Radiolabeled micelles having hydrodynamic radius of 97 +/- 13 nm have been successfully evaluated in vivo and ex vivo in non-tumor-bearing mice, revealing significant blood circulation up to at least 24 h post injection, with low accumulation in most organs except for the liver and spleen, which are the natural organs for clearance of nanoparticles. CONCLUSIONS: An easy and robust radiolabeling method has been developed, and its applicability is demonstrated in animal studies, showing its value for future investigation of polymeric micelles as nanocarriers in tumor-bearing mice. PMID- 26860292 TI - EAPD interim seminar and workshop in Brussels May 9 2015 : Non-invasive caries treatment. AB - AIM: This was to collect information for the 9th European Academy of Paediatric Dentistry Interim Seminar and Workshops to discuss the state of art on non invasive caries therapy to be used if possible to formulate clinical guidelines by European experts in paediatric dentistry METHODS: Based on systematic reviews and additional papers were assessed for methods to prevent caries initiation and caries progression both in the state of pre-cavitation and cavitation without invasive technologies. RESULTS: The use of fluoridated water, careful diligent daily use of fluoride toothpaste, fluoride varnishes, pit and fissure sealants and leak-proof restorative materials without excavation of caries are evidence based for caries prevention and for non-invasive treatment of pre-cavitated and cavitated caries. Other technologies are far less evidenced based and would not logically fit in guidelines for the non-invasive treatment of caries. Recent studies on cavitated lesions in the primary dentition demonstrate that thorough oral hygiene practices may arrest progression. This strategy depends heavily on the strategies in the dental surgery to change behaviour of children. An important aspect is for advice to be tailored at recall intervals to ensure compliance and to timely detect unnecessary and unwanted progression of the lesions. CONCLUSION: Non-invasive therapies have been proven to be effective for caries prevention and the management of pre-cavitated caries lesions. Non invasive therapies can also be effective to arrest cavitated lesions but the success depends greatly on behavioural changes of patients to brush the lesions. PMID- 26860295 TI - Contribution of Auger/conversion electrons to renal side effects after radionuclide therapy: preclinical comparison of (161)Tb-folate and (177)Lu folate. AB - BACKGROUND: The radiolanthanide (161)Tb has, in recent years, attracted increasing interest due to its favorable characteristics for medical application. (161)Tb exhibits similar properties to the widely-used therapeutic radionuclide (177)Lu. In contrast to (177)Lu, (161)Tb yields a significant number of short ranging Auger/conversion electrons (<=50 keV) during its decay process. (161)Tb has been shown to be more effective for tumor therapy than (177)Lu if applied using the same activity. The purpose of this study was to investigate long-term damage to the kidneys after application of (161)Tb-folate and compare it to the renal effects caused by (177)Lu-folate. METHODS: Renal side effects were investigated in nude mice after the application of different activities of (161)Tb-folate (10, 20, and 30 MBq per mouse) over a period of 8 months. Renal function was monitored by the determination of (99m)Tc-DMSA uptake in the kidneys and by measuring blood urea nitrogen and creatinine levels in the plasma. Histopathological analysis was performed by scoring of the tissue damage observed in HE-stained kidney sections from euthanized mice. RESULTS: Due to the co emitted Auger/conversion electrons, the mean absorbed renal dose of (161)Tb folate (3.0 Gy/MBq) was about 24 % higher than that of (177)Lu-folate (2.3 Gy/MBq). After application of (161)Tb-folate, kidney function was reduced in a dose- and time-dependent manner, as indicated by the decreased renal uptake of (99m)Tc-DMSA and the increased levels of blood urea nitrogen and creatinine. Similar results were obtained when (177)Lu-folate was applied at the same activity. Histopathological investigations confirmed comparable renal cortical damage after application of the same activities of (161)Tb-folate and (177)Lu folate. This was characterized by collapsed tubules and enlarged glomeruli with fibrin deposition in moderately injured kidneys and glomerulosclerosis in severely damaged kidneys. CONCLUSIONS: Tb-folate induced dose-dependent radionephropathy over time, but did not result in more severe damage than (177)Lu folate when applied at the same activity. These data are an indication that Auger/conversion electrons do not exacerbate overall renal damage after application with (161)Tb-folate as compared to (177)Lu-folate, even though they result in an increased dose deposition in the renal tissue. Global toxicity affecting other tissues than kidneys remains to be investigated after (161)Tb based therapy, however. PMID- 26860297 TI - Bioinorganic Chemistry of the Alkali Metal Ions. AB - The common Group 1 alkali metals are indeed ubiquitous on earth, in the oceans and in biological systems. In this introductory chapter, concepts involving aqueous chemistry and aspects of general coordination chemistry and oxygen atom donor chemistry are introduced. Also, there are nuclear isotopes of importance. A general discussion of Group 1 begins from the prevalence of the ions, and from a comparison of their ionic radii and ionization energies. While oxygen and water molecule binding have the most relevance to biology and in forming a detailed understanding between the elements, there is a wide range of basic chemistry that is potentially important, especially with respect to biological chelation and synthetic multi-dentate ligand design. The elements are widely distributed in life forms, in the terrestrial environment and in the oceans. The details about the workings in animal, as well as plant life are presented in this volume. Important biometallic aspects of human health and medicine are introduced as well. Seeing as the elements are widely present in biology, various particular endogenous molecules and enzymatic systems can be studied. Sodium and potassium are by far the most important and central elements for consideration. Aspects of lithium, rubidium, cesium and francium chemistry are also included; they help in making important comparisons related to the coordination chemistry of Na(+) and K(+). Physical methods are also introduced. PMID- 26860296 TI - Optical imaging of pre-invasive breast cancer with a combination of VHHs targeting CAIX and HER2 increases contrast and facilitates tumour characterization. AB - BACKGROUND: Optical molecular imaging is an emerging novel technology with applications in the diagnosis of cancer and assistance in image-guided surgery. A high tumour-to-background (T/B) ratio is crucial for successful imaging, which strongly depends on tumour-specific probes that rapidly accumulate in the tumour, while non-bound probes are rapidly cleared. Here, using pre-invasive breast cancer as a model, we investigate whether the use of combinations of probes with different target specificities results in higher T/B ratios and whether dual spectral imaging leads to improvements in tumour characterization. METHODS: We performed optical molecular imaging of an orthotopic breast cancer model mimicking ductal carcinoma in situ (DCIS). A combination of carbonic anhydrase IX (CAIX)- and human epidermal growth factor receptor 2 (HER2)-specific variable domains of the heavy chain from heavy-chain antibodies (VHHs) was conjugated either to the same fluorophore (IRDye800CW) to evaluate T/B ratios or to different fluorophores (IRDye800CW, IRDye680RD or IRDye700DX) to analyse the expression of CAIX and HER2 simultaneously through dual-fluorescence detection. These experiments were performed non-invasively in vivo, in a mimicked intra operative setting, and ex vivo on tumour sections. RESULTS: Application of the CAIX- and HER2-specific VHH combination resulted in an increase of the T/B ratio, as compared to T/B ratios obtained from each of these single VHHs together with an irrelevant VHH. This dual tumour marker-specific VHH combination also enabled the detection of small metastases in the lung. Furthermore, dual-spectral imaging enabled the assessment of the expression status of both CAIX and HER2 in a mimicked intra-operative setting, as well as on tumour sections, which was confirmed by immunohistochemistry. CONCLUSIONS: These results establish the feasibility of the use of VHH 'cocktails' to increase T/B ratios and improve early detection of heterogeneous tumours and the use of multispectral molecular imaging to facilitate the assessment of the target expression status of tumours and metastases, both invasive or non-invasively. PMID- 26860298 TI - Determination of Alkali Ions in Biological and Environmental Samples. AB - An overview of the common methods for the determination of the alkali metals is given. These are drawn from all of the three principle branches of quantitative analysis and consist mainly of optical atomic spectrometric methods, ion selective electrodes, and the separation methods of ion-chromatography and capillary electrophoresis. Their main characteristics and performance parameters are discussed. Important specific applications are also examined, namely clinical analysis, single cell analysis, the analysis of soil samples and hydroponic nutrient solutions, as well as the detection of the radioactive (137)Cs isotope. PMID- 26860299 TI - Solid State Structures of Alkali Metal Ion Complexes Formed by Low-Molecular Weight Ligands of Biological Relevance. AB - This chapter provides structural data, mainly metal binding sites/modes, observed in crystal structures of alkali metal ion complexes containing low-molecular weight ligands of biological relevance, mostly obtained from the Cambridge Structural Database (the CSD version 5.35 updated to February 2014). These ligands include (i) amino acids and small peptides, (ii) nucleic acid constituents (excluding quadruplexes and other oligonucleotides), (iii) simple carbohydrates, and (iv) naturally occurring antibiotic ionophores. For some representative complexes of these ligands, some details on the environment of the metal coordination and structural characteristics are described. PMID- 26860300 TI - Discriminating Properties of Alkali Metal Ions Towards the Constituents of Proteins and Nucleic Acids. Conclusions from Gas-Phase and Theoretical Studies. AB - Quantitative insight into the structures and thermodynamics of alkali metal cations interacting with biological molecules can be obtained from studies in the gas phase combined with theoretical work. In this chapter, the fundamentals of the experimental and theoretical techniques are first summarized and results for such work on complexes of alkali metal cations with amino acids, small peptides, and nucleobases are reviewed. Periodic trends in how these interactions vary as the alkali metal cations get heavier are highlighted. PMID- 26860301 TI - Alkali Metal Ion Complexes with Phosphates, Nucleotides, Amino Acids, and Related Ligands of Biological Relevance. Their Properties in Solution. AB - Alkali metal ions play very important roles in all biological systems, some of them are essential for life. Their concentration depends on several physiological factors and is very variable. For example, sodium concentrations in human fluids vary from quite low (e.g., 8.2 mmol dm(-3) in mature maternal milk) to high values (0.14 mol dm(-3) in blood plasma). While many data on the concentration of Na(+) and K(+) in various fluids are available, the information on other alkali metal cations is scarce. Since many vital functions depend on the network of interactions occurring in various biofluids, this chapter reviews their complex formation with phosphates, nucleotides, amino acids, and related ligands of biological relevance. Literature data on this topic are quite rare if compared to other cations. Generally, the stability of alkali metal ion complexes of organic and inorganic ligands is rather low (usually log K < 2) and depends on the charge of the ligand, owing to the ionic nature of the interactions. At the same time, the size of the cation is an important factor that influences the stability: very often, but not always (e.g., for sulfate), it follows the trend Li(+) > Na(+) > K(+) > Rb(+) > Cs(+). For example, for citrate it is: log K ML = 0.88, 0.80, 0.48, 0.38, and 0.13 at 25 degrees C and infinite dilution. Some considerations are made on the main aspects related to the difficulties in the determination of weak complexes. The importance of the alkali metal ion complexes was also studied in the light of modelling natural fluids and in the use of these cations as probes for different processes. Some empirical relationships are proposed for the dependence of the stability constants of Na(+) complexes on the ligand charge, as well as for correlations among log K values of NaL, KL or LiL species (L = generic ligand). PMID- 26860302 TI - Sodium and Potassium Interactions with Nucleic Acids. AB - Metal ions are essential cofactors for the structure and functions of nucleic acids. Yet, the early discovery in the 70s of the crucial role of Mg(2+) in stabilizing tRNA structures has occulted for a long time the importance of monovalent cations. Renewed interest in these ions was brought in the late 90s by the discovery of specific potassium metal ions in the core of a group I intron. Their importance in nucleic acid folding and catalytic activity is now well established. However, detection of K(+) and Na(+) ions is notoriously problematic and the question about their specificity is recurrent. Here we review the different methods that can be used to detect K(+) and Na(+) ions in nucleic acid structures such as X-ray crystallography, nuclear magnetic resonance or molecular dynamics simulations. We also discuss specific versus non-specific binding to different structures through various examples. PMID- 26860303 TI - Role of Alkali Metal Ions in G-Quadruplex Nucleic Acid Structure and Stability. AB - G-quadruplexes are guanine-rich nucleic acids that fold by forming successive quartets of guanines (the G-tetrads), stabilized by intra-quartet hydrogen bonds, inter-quartet stacking, and cation coordination. This specific although highly polymorphic type of secondary structure deviates significantly from the classical B-DNA duplex. G-quadruplexes are detectable in human cells and are strongly suspected to be involved in a number of biological processes at the DNA and RNA levels. The vast structural polymorphism exhibited by G-quadruplexes, together with their putative biological relevance, makes them attractive therapeutic targets compared to canonical duplex DNA. This chapter focuses on the essential and specific coordination of alkali metal cations by G-quadruplex nucleic acids, and most notably on studies highlighting cation-dependent dissimilarities in their stability, structure, formation, and interconversion. Section 1 surveys G quadruplex structures and their interactions with alkali metal ions while Section 2 presents analytical methods used to study G-quadruplexes. The influence of alkali cations on the stability, structure, and kinetics of formation of G quadruplex structures of quadruplexes will be discussed in Sections 3 and 4. Section 5 focuses on the cation-induced interconversion of G-quadruplex structures. In Sections 3 to 5, we will particularly emphasize the comparisons between cations, most often K(+) and Na(+) because of their prevalence in the literature and in cells. PMID- 26860304 TI - Sodium and Potassium Ions in Proteins and Enzyme Catalysis. AB - The group I alkali metal ions Na(+) and K(+) are ubiquitous components of biological fluids that surround biological macromolecules. They play important roles other than being nonspecific ionic buffering agents or mediators of solute exchange and transport. Molecular evolution and regulated high intracellular and extracellular M(+) concentrations led to incorporation of selective Na(+) and K(+) binding sites into enzymes to stabilize catalytic intermediates or to provide optimal positioning of substrates. The mechanism of M(+) activation, as derived from kinetic studies along with structural analysis, has led to the classification of cofactor-like (type I) or allosteric effector (type II) activated enzymes. In the type I mechanism substrate anchoring to the enzyme active site is mediated by M(+), often acting in tandem with a divalent cation like Mg(2+), Mn(2+) or Zn(2+). In the allosteric type II mechanism, M(+) binding enhances enzyme activity through conformational transitions triggered upon binding to a distant site. In this chapter, following the discussion of the coordination chemistry of Na(+) and K(+) ions and the structural features responsible for the metal binding site selectivity in M(+)-activated enzymes, well-defined examples of M(+)-activated enzymes are used to illustrate the structural basis for type I and type II activation by Na(+) and K(+). PMID- 26860305 TI - Roles and Transport of Sodium and Potassium in Plants. AB - The two alkali cations Na(+) and K(+) have similar relative abundances in the earth crust but display very different distributions in the biosphere. In all living organisms, K(+) is the major inorganic cation in the cytoplasm, where its concentration (ca. 0.1 M) is usually several times higher than that of Na(+). Accumulation of Na(+) at high concentrations in the cytoplasm results in deleterious effects on cell metabolism, e.g., on photosynthetic activity in plants. Thus, Na(+) is compartmentalized outside the cytoplasm. In plants, it can be accumulated at high concentrations in vacuoles, where it is used as osmoticum. Na(+) is not an essential element in most plants, except in some halophytes. On the other hand, it can be a beneficial element, by replacing K(+) as vacuolar osmoticum for instance. In contrast, K(+) is an essential element. It is involved in electrical neutralization of inorganic and organic anions and macromolecules, pH homeostasis, control of membrane electrical potential, and the regulation of cell osmotic pressure. Through the latter function in plants, it plays a role in turgor-driven cell and organ movements. It is also involved in the activation of enzymes, protein synthesis, cell metabolism, and photosynthesis. Thus, plant growth requires large quantities of K(+) ions that are taken up by roots from the soil solution, and then distributed throughout the plant. The availability of K(+) ions in the soil solution, slowly released by soil particles and clays, is often limiting for optimal growth in most natural ecosystems. In contrast, due to natural salinity or irrigation with poor quality water, detrimental Na(+) concentrations, toxic for all crop species, are present in many soils, representing 6 % to 10 % of the earth's land area. Three families of ion channels (Shaker, TPK/KCO, and TPC) and 3 families of transporters (HAK, HKT, and CPA) have been identified so far as contributing to K(+) and Na(+) transport across the plasmalemma and internal membranes, with high or low ionic selectivity. In the model plant Arabidopsis thaliana, these families gather at least 70 members. Coordination of the activities of these systems, at the cell and whole plant levels, ensures plant K(+) nutrition, use of Na(+) as a beneficial element, and adaptation to saline conditions. PMID- 26860306 TI - Potassium Versus Sodium Selectivity in Monovalent Ion Channel Selectivity Filters. AB - Transport of Na(+) and K(+) ions across the cell membrane is carried out by specialized pore-forming ion channel proteins, which exert tight control on electrical signals in cells by regulating the inward/outward flow of the respective cation. As Na(+) and K(+) ions are both present in the body fluids, their respective ion channels should discriminate with high fidelity between the two competing metal ions, conducting the native cation while rejecting its monovalent contender (and other ions present in the cellular/extracellular milieu). Indeed, monovalent ion channels are characterized by remarkable metal selectivity. This striking ion selectivity of monovalent ion channels is astonishing in view of the close similarity between Na(+) and K(+): both are spherical alkali cations with the same charge, analogous chemical and physical properties, and similar ionic radii. The monovalent ion channel selectivity filters (SFs), which dictate the selectivity of the channel, differ in oligomericity, composition, overall charge, pore size, and solvent accessibility. This diversity of SFs raises the following intriguing questions: (1) What factors govern the metal competition in these SFs? (2) Which of these factors are exploited in achieving K(+) or Na(+) selectivity in the different types of monovalent channel SFs? These questions are addressed herein by summarizing results from recent studies. The results show that over billions of years of evolution, the SFs of potassium and sodium ion channels have adapted to the specific physicochemical properties of the cognate ion, using various strategies to enable them to efficiently select the native ion among its contenders. PMID- 26860307 TI - Sodium as Coupling Cation in Respiratory Energy Conversion. AB - Among the alkali cations, Na(+) has an extraordinary role in living cells since it is used to charge the battery of life. To this end, sophisticated protein complexes in biological membranes convert chemical energy obtained from oxidation of NADH, or hydrolysis of ATP, into an electrochemical gradient of sodium ions. Cells use this so-called sodium-motive force stored in energy-converting membranes for important processes like uptake of nutrients, motility, or expulsion of toxic compounds. The Na(+) pumps act in concert with other enzymes embedded in the lipid membrane, and together they form the respiratory chain which achieves the oxidation of NADH derived from nutrients under formation of an electrochemical sodium (or proton) gradient. We explain why Na(+) pumps are important model systems for the homologous, proton-translocating complexes, and hope to convince the reader that studying the Na(+)-translocating ATP synthase from the unimpressive bacterium Ilyobacter tartaricus had a big impact on our understanding of energy conversion by human ATP synthase. The Na(+)-translocating systems described here are either driven by the oxidation of NADH, the carrier of redox equivalents of cells, or by the hydrolysis of adenosine 5'-triphosphate, the universal high-energy compound of cells. The electrochemical energy provided by these respiratory Na(+) pumps, the NADH dehydrogenase or the ATPase, drives other Na(+) transport systems like the bacterial flagellum discussed in the last part of this chapter. The flagellar motor does not represent a Na(+) pump, but like ATPase, it operates by a rotational mechanism. By comparing these two Na(+) translocating, rotary machines, we obtain new insight into the possible mechanisms of Na(+) transport through the stator proteins of the flagellar motor. Na(+) pumps are widespread in pathogenic bacteria where they play an important role in metabolism, making them novel targets for antibiotics. PMID- 26860308 TI - Sodium-Proton (Na(+)/H(+)) Antiporters: Properties and Roles in Health and Disease. AB - The transmembranal Na(+)/H(+) antiporters transport sodium (or several other monovalent cations) in exchange for H(+) across lipid bilayers in all kingdoms of life. They are critical in pH homeostasis of the cytoplasm and/or organelles. A particularly notable example is the SLC9 gene family, which encodes Na(+)/H(+) exchangers (NHEs) in many species from prokaryotes to eukaryotes. In humans, these proteins are associated with the pathophysiology of various diseases. Yet, the most extensively studied Na(+)/H(+) antiporter is Ec-NhaA, the main Na(+)/H(+) antiporter of Escherichia coli.The crystal structure of down-regulated Ec-NhaA, determined at acidic pH, has provided the first structural insights into the antiport mechanism and pH regulation of an Na(+)/H(+) antiporter. It reveals a unique structural fold (called the NhaA fold) in which transmembrane segments (TMs) are organized in inverted-topology repeats, including two antiparallel unfolded regions that cross each other, forming a delicate electrostatic balance in the middle of the membrane. This unique structural fold (The NhaA fold) contributes to the cation binding site and facilitates the rapid conformational changes expected for Ec-NhaA. The NhaA fold has now been recognized to be shared by four Na(+)/H(+) antiporters (bacterial and archaeal) and a Na(+) symporter. Remarkably, no crystal structure of any of the human Na(+)/H(+) antiporters exists. Nevertheless, the Ec-NhaA crystal structure has enabled the structural modeling of NHE1, NHE9, and NHA2, three human plasmalemmal proteins that are members of the SLC9 family that are involved in human pathophysiology. Moreover, as outlined in this review, developments in the field, including cellular and biophysical methods that enable ion levels and fluxes to be measured in intact cells as well as in knockout mice, have led to striking advances in the identification and characterization of plasma membrane NHEs and NHA.Very little is known about the endomembrane isoforms of NHE. These intracellular exchangers may serve a function in cation homeostasis and/or osmoregulation, and not in pH regulation as is the case for the plasmalemmal isoforms. This intriguing possibility should be borne in mind when designing future studies. Future progress towards gaining an understanding of the SLC9 gene family, including its structure-function relationships and regulatory mechanisms in health and in disease, is likely to include insights into the pathophysiology of multiple diseases. PMID- 26860309 TI - Proton-Potassium (H(+)/K(+)) ATPases: Properties and Roles in Health and Diseases. AB - As a physiological phenomenon, acid secretion from the stomach was known already at least in the 17th century. But its mechanism was elucidated in more recent times only. At the end of the 20th century, gastric H(+)/K(+)-ATPase in the parietal cells was found to be responsible for a final step of H(+) secretion in these cells. In this century, several Cl(-)-transporting proteins for gastric acid (hydrochloric acid; HCl) secretion have been found. As inhibitors of gastric acid secretion, histamine H2 receptor antagonists (H2 blockers) were developed in the 1970's. This discovery brought a great benefit; that is, peptic ulcers became treatable by administration of a drug. In 1980's, proton pump inhibitors (PPIs) were developed. The target of PPIs is gastric H(+)/K(+)-ATPase and the PPIs exert generally more potent effects compared with H2 blockers. Most recently, several K(+)-competitive inhibitors of the ATPase are being developed. Here, we introduce gastric H(+)/K(+)-ATPase and its related proteins for gastric acid secretion, and several gastric diseases and their treatment by medicines. PMID- 26860310 TI - Bioinspired Artificial Sodium and Potassium Ion Channels. AB - In Nature, all biological systems present a high level of compartmentalization in order to carry out a wide variety of functions in a very specific way. Hence, they need ways to be connected with the environment for communication, homeostasis equilibrium, nutrition, waste elimination, etc. The biological membranes carry out these functions; they consist of physical insulating barriers constituted mainly by phospholipids. These amphipathic molecules spontaneously aggregate in water to form bilayers in which the polar groups are exposed to the aqueous media while the non-polar chains self-organize by aggregating to each other to stay away from the aqueous media. The insulating properties of membranes are due to the formation of a hydrophobic bilayer covered at both sides by the hydrophilic phosphate groups. Thus, lipophilic molecules can permeate the membrane freely, while the small charged or very hydrophilic molecules require the assistance of other membrane components in order to overcome the energetic cost implied in crossing the non-polar region of the bilayer. Most of the large polar species (such as oligosaccharides, polypeptides or nucleic acids) cross into and out of the cell via endocytosis and exocytosis, respectively. Nature has created a series of systems (carriers and pores) in order to control the balance of small hydrophilic molecules and ions. The most important structures to achieve these goals are the ionophoric proteins that include the channel proteins, such as the sodium and potassium channels, and ionic transporters, including the sodium/potassium pumps or calcium/sodium exchangers among others. Inspired by these, scientists have created non-natural synthetic transporting structures to mimic the natural systems. The progress in the last years has been remarkable regarding the efficient transport of Na(+) and K(+) ions, despite the fact that the selectivity and the ON/OFF state of the non-natural systems remain a present and future challenge. PMID- 26860312 TI - Sodium and Potassium Relating to Parkinson's Disease and Traumatic Brain Injury. AB - Alkali metals, especially sodium and potassium, are plentiful and vital in biological systems. They take on important roles in health and disease. Such roles include the regulation of homeostasis, osmosis, blood pressure, electrolytic equilibria, and electric current. However, there is a limit to our present understanding; the ions have a great ability and capacity for action in health and disease, much greater than our current understanding. For the regulation of physiological homeostasis, there is a crucial regulator (renin angiotensin system, RAS), found at both peripheral and central levels. Misregulation of the Na(+)-K(+) pump, and sodium channels in RAS are important for the understanding of disease progression, hypertension, diabetes, and neurodegenerative diseases, etc. In particular, RAS displays direct or indirect interaction important to Parkinson's disease (PD). In this chapter, the relationship between the regulation of sodium/potassium concentration and PD was sought. In addition, some recent biochemical and clinical findings are also discussed that help describe sodium and potassium in the context of traumatic brain injury (TBI). TBI is caused from the heavy striking of the head; this strongly affects ion flux in the affected tissue (brain) and damages cellular regulation systems. Thus, inappropriate concentrations of ions (hyper- and hyponatremia, and hyper- and hypokalemia) will perturb homeostasis giving rise to important and far reaching effects. These changes also impact osmotic pressure and the concentration of other metal ions, such as the calcium(II) ion. PMID- 26860311 TI - Lithium in Medicine: Mechanisms of Action. AB - In this chapter, we review the mechanism of action of lithium salts from a chemical perspective. A description on how lithium salts are used to treat mental illnesses, in particular bipolar disorder, and other disease states is provided. Emphasis is not placed on the genetics and the psychopharmacology of the ailments for which lithium salts have proven to be beneficial. Rather we highlight the application of chemical methodologies for the characterization of the cellular targets of lithium salts and their distribution in tissues. PMID- 26860313 TI - Epidemiology, impact and control of bovine cysticercosis in Europe: a systematic review. AB - BACKGROUND: Bovine cysticercosis in Europe has been known for centuries but the data showing the occurrence of this zoonosis are scarce. The aim of this paper is to review and present the current knowledge on bovine cysticercosis in Europe. METHODS: We conducted a systematic review of studies published between 1990 and November 2014. Qualitative and quantitative data on prevalence, risk factors, burden and interventions were extracted and analysed. RESULTS: Reports on prevalence were available for 23 European countries, mostly from western and central Europe; for a few of these only data before 1990 were available. Prevalence based on meat inspection was generally low (below 6.2% in 95% of the records) and varied between and within countries. Serology and detailed meat inspection provided a higher prevalence range (0.41-14%). Only few studies analysing risk factors were identified. Reported factors related to access to pastures and risky waters, dairy production and uncontrolled human defecation in the proximity of the farm among others. Only one estimate of the economic impact of the disease could be identified. Recommended interventions were focused on increasing diagnostic tests sensitivity or the application of risk based surveillance strategies. CONCLUSIONS: There is a lack of complete and updated data on most countries, especially in eastern Europe. Further risk factor studies might be needed together with estimates on the burden of the disease in all European countries. Risk-based interventions are being encouraged but current data are limited to guide this approach. PMID- 26860314 TI - Proteomic changes induced by potassium deficiency and potassium substitution by sodium in sugar beet. AB - In this study, sugar beets (Beta vulgaris L.) were grown at different K(+)/Na(+) concentrations: mmol/L, 3/0 (control); 0.03/2.97 (K-Na replacement group; T(rep)); 0.03/0 (K deficiency group; T(def)) in order to investigate the effects of K(+) deficiency and replacement of K(+) by Na(+) on plant proteomics, and to explore the physiological processes influenced by Na(+) to compensate for a lack of K(+). After 22 days, fresh and dry weight as well as the Na(+) and K(+) concentration were measured and changes in proteomics were tested by 2D gel electrophoresis. Interestingly, Na(+) showed stimulation in growth of seedlings and hindrance of K(+) assimilation in T(rep). Significant changes were also observed in 27 protein spots among the treatments. These are proteins involved in photosynthesis, cellular respiration, protein folding and degradation, stress and defense, other metabolisms, transcription related, and protein synthesis. A wide range of physiological processes, including light reaction, CO2 assimilation, glycolysis, and tricaboxylic acid cycle, was impaired owing to K(+) starvation. Compensating for the effect of K(+) starvation, an increase in photosynthesis was also observed in T(rep). However, we also found a limitation of cellular respiration by Na(+). Na(+) is therefore in some ways able to recover damage due to K deficiency at protein level, but cannot functionally replace K as an essential nutrient. PMID- 26860315 TI - Unilateral congenital giant megaureter with renal dysplasia compressing contralateral ureter and causing bilateral hydronephrosis: a case report and literature review. AB - BACKGROUND: Congenital giant megaureter (CGM) is uncommon in the pediatric population. The major clinical presentations are marked protruberances and abdominal cysts. CASE PRESENTATION: We reported a case of CGM with almost the whole left ureter dilation accompanied with a 1 cm stricture at the entrance of the bladder and renal dysplasia, immediately compressing the contralateral ureter and causing bilateral hydronephrosis for the first time. At one-stage of the operation, a left nephrostomy with a right ureterolysis were performed, and a poor left kidney function was found. Then, the left kidney and ureter were cut off by nephroureterectomy at the second-stage. Eventually, the follow-up showed that the patient recovered well by abdominal ultrasound. CONCLUSION: Based on the findings of these reported literatures, CGM is rare. The physical and imaging examinations are essential for the diagnosis of CGM, and the appropriate treatment methods should be performed based on patients' specific condition. PMID- 26860317 TI - Comment to: Haemodialysis session: The perfect storm for vascular calcification. PMID- 26860316 TI - Novel nuclear-cytoplasmic interaction in wheat (Triticum aestivum) induces vigorous plants. AB - Interspecific hybridization can be considered an accelerator of evolution, otherwise a slow process, solely dependent on mutation and recombination. Upon interspecific hybridization, several novel interactions between nuclear and cytoplasmic genomes emerge which provide additional sources of diversity. The magnitude and essence of intergenomic interactions between nuclear and cytoplasmic genomes remain unknown due to the direction of many crosses. This study was conducted to address the role of nuclear-cytoplasmic interactions as a source of variation upon hybridization. Wheat (Triticum aestivum) alloplasmic lines carrying the cytoplasm of Aegilops mutica along with an integrated approach utilizing comparative quantitative trait locus (QTL) and epigenome analysis were used to dissect this interaction. The results indicate that cytoplasmic genomes can modify the magnitude of QTL controlling certain physiological traits such as dry matter weight. Furthermore, methylation profiling analysis detected eight polymorphic regions affected by the cytoplasm type. In general, these results indicate that novel nuclear-cytoplasmic interactions can potentially trigger an epigenetic modification cascade in nuclear genes which eventually change the genetic network controlling physiological traits. These modified genetic networks can serve as new sources of variation to accelerate the evolutionary process. Furthermore, this variation can synthetically be produced by breeders in their programs to develop epigenomic-segregating lines. PMID- 26860318 TI - Radiologic Improvement After Early Medical Intervention in Localised Facial Morphea. AB - We report the case of a young girl who presented with hemiparesis, seizures, and subtle features consistent with a linear form of facial morphea (en coup de sabre). She was treated with pulsed parenteral steroids and oral steroids and started on methotrexate. Magnetic resonance imaging results and neurologic problems improved after 6 months. Switching off inflammation early in the course of disease seemed to reverse some of the central nervous system changes. Assessment of children with unexplained hemiparesis and seizures should include careful examination of the face and scalp, looking for subtle signs of skin change and asymmetry. This is one of the few reported cases of neuroradiologic improvement after immunosuppressive treatment in a child with en coup de sabre. PMID- 26860319 TI - LowMACA: exploiting protein family analysis for the identification of rare driver mutations in cancer. AB - BACKGROUND: The increasing availability of resequencing data has led to a better understanding of the most important genes in cancer development. Nevertheless, the mutational landscape of many tumor types is heterogeneous and encompasses a long tail of potential driver genes that are systematically excluded by currently available methods due to the low frequency of their mutations. We developed LowMACA (Low frequency Mutations Analysis via Consensus Alignment), a method that combines the mutations of various proteins sharing the same functional domains to identify conserved residues that harbor clustered mutations in multiple sequence alignments. LowMACA is designed to visualize and statistically assess potential driver genes through the identification of their mutational hotspots. RESULTS: We analyzed the Ras superfamily exploiting the known driver mutations of the trio K N-HRAS, identifying new putative driver mutations and genes belonging to less known members of the Rho, Rab and Rheb subfamilies. Furthermore, we applied the same concept to a list of known and candidate driver genes, and observed that low confidence genes show similar patterns of mutation compared to high confidence genes of the same protein family. CONCLUSIONS: LowMACA is a software for the identification of gain-of-function mutations in putative oncogenic families, increasing the amount of information on functional domains and their possible role in cancer. In this context LowMACA emphasizes the role of genes mutated at low frequency otherwise undetectable by classical single gene analysis. LowMACA is an R package available at http://www.bioconductor.org/packages/release/bioc/html/LowMACA.html. It is also available as a GUI standalone downloadable at: https://cgsb.genomics.iit.it/wiki/projects/LowMACA. PMID- 26860321 TI - Aptamer and Antisense-Mediated Two-Dimensional Isolation of Specific Cancer Cell Subpopulations. AB - Cancer cells, and in particular those found circulating in blood, can have widely varying phenotypes and molecular profiles despite a common origin. New methods are needed that can deconvolute the heterogeneity of cancer cells and sort small numbers of cells to aid in the characterization of cancer cell subpopulations. Here, we describe a new molecular approach to capturing cancer cells that isolates subpopulations using two-dimensional sorting. Using aptamer-mediated capture and antisense-triggered release, the new strategy sorts cells according to levels of two different markers and thereby separates them into their corresponding subpopulations. Using a phenotypic assay, we demonstrate that the subpopulations isolated have markedly different properties. This system provides an important new tool for identifying circulating tumor cell subtypes. PMID- 26860320 TI - Effective treatment with rituximab for the maintenance of remission in frequently relapsing minimal change disease. AB - AIM: Treatment of frequently relapsing or steroid-dependent minimal change disease (MCD) in children and adults remains challenging. Glucocorticoids and/or other immunosuppressive agents are the mainstay of treatment, but patients often experience toxicity from prolonged exposure and may either become treatment dependent and/or resistant. Increasing evidence suggests that rituximab (RTX) can be a useful alternative to standard immunosuppression and allow withdrawal of maintenance immunosuppressants; however, data on optimal treatment regimens, long term efficacy and safety are still limited. METHODS: We undertook a prospective study of RTX to allow immunosuppression minimization in 15 young adults with frequently relapsing or steroid-dependent, biopsy-proven MCD. All patients were in remission at the start of treatment and on a calcineurin inhibitor. Two doses of RTX (1 gr) were given 6 months apart. A subset of patients also received an additional dose 12 months later, in order to examine the benefit of re-treatment. Biochemical and clinical parameters were monitored over an extended follow-up period of up to 43 months. RESULTS: Median steroid-free survival after RTX was 25 months (range 4-34). Mean relapse frequency decreased from 2.60 +/- 0.28 to 0.4 +/- 0.19 (P < 0.001) after RTX. Seven relapses occurred, five of which (71%) when CD19 counts were greater than 100 u. Immunoglobulin levels remained unchanged, and no major side effects were observed throughout the follow-up period. CONCLUSIONS: Rituximab therapy is effective at maintaining prolonged steroid-free remission and reducing relapse frequency in this group of patients. Our study lends further support for the role of RTX in the treatment of patients with frequently relapsing or steroid-dependent MCD. PMID- 26860322 TI - Vitamin D and Its Relevance in the Etiopathogenesis of Oral Cavity Diseases. AB - Vitamin D belongs to a group of fat-soluble secosteroids which assume many roles in the human organism. In humans the most important forms are vitamin D3 and vitamin D2. Their primary function is the regulation of the calcium and phosphorus balance, which promote the growth of healthy bony tissue. Studies over the past few years have revealed a much wider role of vitamin D involving the aging processes, carcinogenesis, the carbohydrate balance as well as the effects on the course of various infections. In this paper we discuss the basic functions of vitamin D in the human body and the mechanisms of its activity and we summarize recent reports on the impact of vitamin D on the oral cavity with a special emphasis on autoimmunologic diseases, including: recurrent aphthous stomatitis, Behcet syndrome and Sjogren syndrome. PMID- 26860324 TI - From "herbal highs" to the "heroin of cannabis": Exploring the evolving discourse on synthetic cannabinoid use in a Norwegian Internet drug forum. AB - BACKGROUND: In the early 2000s, online vendors began selling an array of so called "legal highs"--apparently organic produce made from exotic herbs. Simultaneously, members of online drug discussion forums began to debate the alleged effects of the new drugs, creating an enormous base of user-derived information based on personal experiences. METHODS: This study combines the historical data spanning a seven-year period derived from a Norwegian drug discussion forum about synthetic cannabinoids and interviews with 14 male forum members who all had experience with the drug. By combining the two sources, this study reveals not only the evolving discourse on synthetic cannabinoid use but also how forum members related to the online information that they gathered and co-produced. RESULTS: Analysis of the evolving online discourse revealed three distinct phases. The first was an enthusiastic phase, with users embracing the new drugs. The second was a phase characterized by growing ambivalence and scepticism towards use of the drugs. The third was one in which members of the community rejected the new drugs based on negative reviews from users. CONCLUSION: The analysis displays the communal process whereby members co-operate in the exchange of an extensive body of knowledge accumulated about synthetic cannabinoids, and the way in which this evolving discourse influences members of the forum in their views and representations of the drugs. Paradoxically, the online discussions of synthetic cannabinoids, which had great significance for their proliferation when they were initially introduced to the market, now seem to be a deterrent. The role of online drug communities in the development of new drug trends should receive renewed attention. PMID- 26860323 TI - Radiation-induced mesothelioma among long-term solid cancer survivors: a longitudinal analysis of SEER database. AB - We investigated the association between external beam radiotherapy (EBRT) and pleural and peritoneal mesothelioma among long-term (>5 years) solid cancer survivors. We analyzed data from the US Surveillance, Epidemiology, and End Results (SEER) program (1973-2012). We fitted survival models adjusted by age, gender, race, year, surgery, and relative risk of primary mesothelioma in the county of residence (proxy for individual asbestos exposure). We estimated hazard ratios [HR] with reference to nonirradiated patients. We distinguished between scattered and direct irradiation to study the dose-response. We observed 301 mesotheliomas (265 pleural; 32 peritoneal; 4 others) among 935,637 patients. EBRT increased the risk of mesothelioma (any site; HR 1.34, 95% CI 1.04-1.77). We observed an increased risk of pleural mesothelioma (HR for EBRT 1.34, 95% CI 1.01 1.77), but we did not find signs of a dose-response relationship (HR for scattered irradiation 1.38; HR for direct irradiation 1.23). On the opposite, only direct peritoneal irradiation was associated with peritoneal mesothelioma (HR 2.20, 95% CI 0.99-4.88), particularly for latencies >=10 years (HR 3.28, 95% CI 1.14-9.43). A competing risks analysis revealed that the clinical impact of radiation-induced mesothelioma was limited by the high frequency of competing events. The cumulative incidence function of mesothelioma after 40 years of observation was very low (nonirradiated patients 0.00032, irradiated patients 0.00055).EBRT might be a determinant of mesothelioma. Longer latency periods are associated with higher risks, while the dose-response seems nonlinear. The clinical impact of mesothelioma after EBRT for primary solid cancers is limited. PMID- 26860325 TI - Poly-drug trafficking: Estimating the scale, trends and harms at the Australian border. AB - BACKGROUND: International drug law enforcement agencies have identified an apparent rise in high level drug traffickers choosing to deal in multiple different drugs. It is hypothesised that this may be a "deliberate modus operandi" and that the formation of "portfolios of trades" may make such traffickers more profitable, harmful and resilient to changes in drug supply and policing. In this paper we provide the first exploration of the extent, nature and harms of poly-drug trafficking at Australian borders. METHODS: Two different methods were used. First, we used Australian Federal Police (AFP) data on all commercial level seizures at the Australian border from 1999 to 2012 to identify the proportion of seizures that were poly-drug and trends over time. Second, we used unit-record data on a sub-set of 20 drug trafficking cases and linked-cases (defined as the original drug trafficking case and all other criminal cases that were connected via common offenders and/or suspects) to compare the profiles of poly-drug and mono-drug traffickers, including: the total weight and type of drug seized, the value of assets seized, and the level of involvement in other crime (such as money laundering and corruption). RESULTS: Between 5% and 35% of commercial importations at the Australian border involved poly-drug trafficking. Poly-drug trafficking occurred in almost every year of analysis (1999-2012), but it increased only slightly over time. Compared to mono-drug traffickers poly-drug traffickers were characterised by: larger quantities of drugs seized, larger networks, longer criminal histories and more involvement in other types of serious crime. CONCLUSION: Some fears about poly-drug traffickers may have been overstated particularly about the inherent escalation of this form of trafficking. Nevertheless, this suggests poly-drug traffickers are likely to pose added risks to governments and law enforcement than mono-drug traffickers. They may necessitate different types of policy responses. PMID- 26860326 TI - HIV prevalence and risk among people who inject drugs in five South African cities. AB - BACKGROUND: Policy and programming for people who inject drugs (PWID) in South Africa is limited by the scarcity of epidemiological data. METHODS: We conducted a cross-sectional survey among 450 PWID (362 males and 88 females) from five South African cities in 2013, using outreach and peer referral to recruit participants. We carried out rapid HIV tests on participants' saliva and assessed drug-using and sexual practices by means of a questionnaire. RESULTS: We found that 26% of females and 13% of males reported to always share injecting equipment, while 49% of all participants had used contaminated injecting equipment the last time they injected. Only 6% of participants usually used bleach to clean their injecting equipment. We found that half of participants reported using a condom the last time they had sex. A quarter of participants reported symptoms of a sexually transmitted infection (STI) in the previous 12 months and 22% had ever worked as a sex worker (51% of females). HIV prevalence among participants was 14% (18% among females and 13% among males). In multivariate analysis HIV was significantly associated with being 25 years and older (adjusted odds ratio (aOR) 2.1, 95% confidence interval (CI) 1.0-4.6, p=0.06), belonging to a racial group other than white (aOR 4.2, 95% CI 1.9-9.4, p<0.001), coming from Gauteng province (aOR 2.3, 95% CI 1.1-5.5, p=0.023), having ever worked as a sex worker (aOR 3.4, 95% CI 1.7-7.2, p=0.001) and the presence of STI symptoms in the last 12 months (aOR 2.4, 95% CI 1.1-4.4, p=0.019). CONCLUSIONS: This study highlights the need for increased access to sterile injecting equipment, education around safer injecting practices and access to sexual and reproductive health services for PWID in South Africa. Programmes for PWID should also address the specific needs of female PWID, PWID who sell sex and PWID from previously disadvantaged communities. PMID- 26860327 TI - A survey of wild plant species for food use in Sicily (Italy) - results of a 3 year study in four Regional Parks. AB - BACKGROUND: This paper illustrates the results of a study carried out in four Regional Parks of Sicily (Italy), concerning traditional knowledge on food use of wild plant species. The main aims of the paper were: (i) to verify which wild plant species are used for food purpose in the local culture based on information provided by elderly inhabitants (ii) to verify the presence of wild plant species which have not been cited for food use in previous studies in the Mediterranean area (iii) to determine how many of the most frequently cited wild plant species are cultivated by the local population in the four Sicilian Parks. METHODS: Semi structured interviews were carried out in the local communities of the four Regional Parks between 2007 and 2010. A total of 802 people over the age of 60 were interviewed. Cultural Importance Index was used to evaluate the level of importance given to any wild plant species as a food in the local culture. The level of appreciation of the wild plant species and the possible effects of wild plants on human health were also investigated. RESULTS: Local communities currently use a total number of 119 wild species for food purposes. Asteraceae and Brassicaceae were the most represented botanical families. In each of the four Sicilian Parks, Cichorium intybus L. and Foeniculum vulgare Mill. obtained the highest Cultural Importance Index values. Sixty-four species were indicated as also having medicinal properties. Leaves and other aerial plant parts were the parts most-used for the preparation of traditional recipes. CONCLUSIONS: The research shows that the level of traditional knowledge on the food uses of wild plant species in the study area is poor. The food uses of plants which are most likely to survive over time are those at the interface of food and medicine. Further agronomic studies are needed for a number of species with a view to introducing them as a crop into non-intensive agricultural systems. PMID- 26860329 TI - A comparison of Clostridium difficile diagnostic methods for identification of local strains in a South African centre. AB - Accurate diagnosis of Clostridium difficile infection is essential for disease management. A clinical and molecular analysis of C. difficile isolated from symptomatic patients at Groote Schuur Hospital, South Africa, was conducted to establish the most suitable clinical test for the diagnosis and characterization of locally prevalent strains. C. difficile was detected in stool samples using enzyme-based immunoassays (EIA) and nucleic acid amplification methods, and their performance was compared with that of C. difficile isolation using direct selective culture combined with specific PCR to detect the C. difficile tpi gene, toxin A and B genes and binary toxin genes. Toxigenic isolates were characterized further by ribotyping. Selective culture isolated 32 C. difficile strains from 145 patients (22 %). Of these, the most prevalent (50 %) were of ribotype 017 (toxin A- B+) while 15.6 % were ribotype 001 (toxin A+B+). No ribotype 027 strains or binary toxin genes (cdtA and cdtB) were detected. The test sensitivities and specificities, respectively, of four commercial clinical diagnostic methods were as follows: ImmunoCard Toxins A & B (40 % and 99.1 %), VIDAS C. difficile Toxin A & B (50 % and 99.1 %), GenoType CDiff (86.7 % and 88.3 %) and Xpert C. difficile (90 % and 97.3 %). Ribotype 001 and 017 strains had a 100 % detection rate by Xpert C. difficile, 100 % and 93.3 % by GenoType CDiff, 75 % and 53.3 % by ImmunoCard and 75 % and 60 % by VIDAS, respectively. The overall poor performance of EIA suggests that a change to PCR-based testing would assist diagnosis and ensure reliable detection of locally prevalent C. difficile 017 strains. PMID- 26860330 TI - A Potential Mechanism of Zhuang Jing Decoction Exerting Therapeutic Effects for Learning and Memory Deficits. PMID- 26860328 TI - Animal modeling an oligodendrogliopathy--multiple system atrophy. AB - Multiple system atrophy (MSA) is a rare, yet rapidly-progressive neurodegenerative disease that presents clinically with autonomic failure in combination with parkinsonism or cerebellar ataxia. The definitive neuropathology differentiating MSA from Lewy body diseases is the presence of alpha-synuclein aggregates in oligodendrocytes (called glial cytoplasmic inclusion or GCI) rather than the fibrillar aggregates in neurons (called Lewy bodies). This makes the pathological pathway(s) in MSA unique in that oligodendrocytes are involved rather than predominantly neurons, as is most other neurodegenerative disorders. MSA is therefore regarded as an oligodendrogliopathy. The etiology of MSA is unknown. No definitive risk factors have been identified, although alpha synuclein and other genes have been variably linked to MSA risk. Utilization of postmortem brain tissues has greatly advanced our understanding of GCI pathology and the subsequent neurodegeneration. However, extrapolating the early pathogenesis of MSA from such resource has been difficult and limiting. In recent years, cell and animal models developed for MSA have been instrumental in delineating unique MSA pathological pathways, as well as aiding in clinical phenotyping. The purpose of this review is to bring together and discuss various animal models that have been developed for MSA and how they have advanced our understanding of MSA pathogenesis, particularly the dynamics of alpha-synuclein aggregation. This review will also discuss how animal models have been used to explore potential therapeutic avenues for MSA, and future directions of MSA modeling. PMID- 26860332 TI - Four hour waiting time for acute psychiatric care urged. PMID- 26860331 TI - Sodium oxybate plus nalmefene for the treatment of alcohol use disorder: A case series. AB - The treatment of alcohol use disorder still remains a challenge. The efficacy of the combined pharmacological treatment for alcohol use disorder has been widely investigated with controversial results. The aim of our case series was to investigate the effect of nalmefene in patients not responding to sodium oxybate therapy. We describe seven cases of consecutive patients affected by alcohol use disorder, and treated with sodium oxybate (50 mg/kg per day) who did not achieve complete alcohol abstinence after at least one month of pharmacological treatment. Then, in partial- and non-responder patients to sodium oxybate treatment, administration of nalmefene, 18 mg as needed, was commenced. Our data show that, during the first month of the combined treatment of sodium oxybate plus nalmefene, patients were able to achieve alcohol abstinence (two patients), to suppress (five cases) or reduce (two patients) episodes of heavy drinking days, and to suppress the onset of craving for sodium oxybate (one patient). Likely, nalmefene may act in modulating the excessive reward effect of sodium oxybate, which may be responsible for the persistence of alcohol intake and for the onset of craving for sodium oxybate. However, controlled clinical trials to confirm the safety and efficacy of sodium oxybate plus nalmefene in treating alcohol use disorder are warranted. PMID- 26860333 TI - An eHealth Platform to Manage Chronic Disease in Primary Care: An Innovative Approach. AB - The number of individuals with chronic illness and multimorbidity is growing due to the rapid ageing of the population and the greater longevity of individuals. This causes an increasing workload in care, which results in a growing need for structural changes of the health care system. In recent years this led to a strong focus on promoting "self-management" in chronically ill patients. Research showed that patients who understand more about their disease, health, and lifestyle have better experiences and health outcomes, and often use less health care resources; the effect is even more when these patients are empowered to and responsible for managing their health and disease. In addition to the skills of patients, health care professionals need to shift to a role of teacher, partner, and professional supervisor of their patients. One way of supervising patients is by the use of electronic health (eHealth), which helps patients manage and control their disease. The application of eHealth solutions can provide chronically ill patients high-quality care, to the satisfaction of both patients and health care professionals, alongside a reduction in health care consumption and costs. PMID- 26860335 TI - In situ vaccination for the treatment of cancer. AB - Vaccination has had a tremendous impact on human health by harnessing the immune system to prevent and eradicate infectious diseases and this same approach might be used in cancer therapy. Cancer vaccine development has been slowed hindered by the paucity of universal tumor-associated antigens and the difficulty in isolating and preparing individualized vaccines ex vivo. Another approach has been to initiate or stimulate an immune response in situ (at the tumor site) and thus exploit the potentially numerous tumor-associated antigens there. Here, we review the many approaches that have attempted to accomplish effective in situ vaccination, using intratumoral administration of immunomodulators to increase the numbers or activation state of either antigen present cells or T cells within the tumor. PMID- 26860334 TI - Community correctional agents' views of medication-assisted treatment: Examining their influence on treatment referrals and community supervision practices. AB - BACKGROUND: Alcohol and opioid use disorders are common among adults under community supervision. Although several medications (medication-assisted treatment or MAT) are Food and Drug Administration (FDA)-approved to treat such disorders, they are underutilized with this population despite established effectiveness at decreasing substance use. This paper examines how community correctional agents' understanding of addiction and views of MAT influence their professional actions regarding addiction medications. METHODS: A total of 118 semistructured qualitative interviews were conducted with community correctional agents taking part in the CJ-DATS MATICCE implementation study across 20 parole/probation offices in 9 US states. Using grounded theory methodology and an iterative analytic approach, issues of role perception, views of MAT, current treatment referral, and community supervision practices were explored. RESULTS: Agents often had limited autonomy to make direct treatment referrals, regardless of their views of MAT, as they were required to follow court orders and their organization's policies and procedures. Within some organizations, community correctional agents held sufficient autonomy to make direct treatment referrals, with agents struggling to reconcile their desire to support their clients who needed MAT with concerns about the abuse potential of opioid agonist medications. Viewing MAT as a "treatment of last resort" was counterbalanced by the view that it was an effective evidence-based practice. Agents described how MAT impacted their ability to supervise clients and how their knowledge and understanding of MAT was directly influenced by watching their clients who were successful or unsuccessful on MAT. Even those agents who were more accepting of MAT were largely unsupportive of it long-term use. CONCLUSIONS: Community correctional agents' views of MAT were influenced by their understanding of addiction as well as their experiences supervising clients receiving treatment with medications, but whether or not MAT referrals were made was not always within their control. PMID- 26860337 TI - Survival of breast cancer patients according to changes in expression of selected markers between primary tumor and lymph node metastases. AB - BACKGROUND: The differences between primary and metastatic tumor cells might be important for treatment selection and prognostication. MATERIALS & METHODS: Expression of ER, PR, HER2, CK5/6, EGFR, Ki-67, Ep-CAM, P-cadherin, CD24, CD44, ALDH was assessed immunohistochemically in primary tumor (T) and corresponding synchronous nodal metastases (LNM) in 156 invasive ductal breast cancer patients (T >=1, N >=1, M0). RESULTS: Independent negative prognostic factors for disease free survival were pN3, ALDH immunopositivity in LNM, nonluminal A subtype in LNM, reduction of Ep-CAM expression in LNM, lack of changes or enhancement of CK5/6 and ALDH expression in LNM. DISCUSSION: Our results suggest that in some cases expression of markers in lymph node metastases might bring additional prognostic information to that obtained from primary tumor. PMID- 26860338 TI - Recovering complete mitochondrial genome sequences from RNA-Seq: A case study of Polytomella non-photosynthetic green algae. AB - Thousands of mitochondrial genomes have been sequenced, but there are comparatively few available mitochondrial transcriptomes. This might soon be changing. High-throughput RNA sequencing (RNA-Seq) techniques have made it fast and cheap to generate massive amounts of mitochondrial transcriptomic data. Here, we explore the utility of RNA-Seq for assembling mitochondrial genomes and studying their expression patterns. Specifically, we investigate the mitochondrial transcriptomes from Polytomella non-photosynthetic green algae, which have among the smallest, most reduced mitochondrial genomes from the Archaeplastida as well as fragmented rRNA-coding regions, palindromic genes, and linear chromosomes with telomeres. Isolation of whole genomic RNA from the four known Polytomella species followed by Illumina paired-end sequencing generated enough mitochondrial-derived reads to easily recover almost-entire mitochondrial genome sequences. Read-mapping and coverage statistics also gave insights into Polytomella mitochondrial transcriptional architecture, revealing polycistronic transcripts and the expression of telomeres and palindromic genes. Ultimately, RNA-Seq is a promising, cost-effective technique for studying mitochondrial genetics, but it does have drawbacks, which are discussed. One of its greatest potentials, as shown here, is that it can be used to generate near-complete mitochondrial genome sequences, which could be particularly useful in situations where there is a lack of available mtDNA data. PMID- 26860339 TI - A dated phylogeny of the papilionoid legume genus Canavalia reveals recent diversification by a pantropical liana lineage. AB - Canavalia is a pantropical legume genus of lianas comprising approximately 60 species distributed in a wide range of habitats. In the last taxonomic revision, the genus was divided into four subgenera: Canavalia (Pantropical), Catodonia (Neotropical, excepting one species also found in the Old World), Maunaloa (Hawaiian), and Wenderothia (Neotropical). In this study, we reconstructed the phylogeny of Canavalia using a broad taxon sampling and analyses of nuclear (ETS and ITS) and plastid markers (trnK/matK). We evaluated the infrageneric classification of the genus and investigated its biogeographical history using molecular dating analyses and ancestral area reconstructions. The phylogenetic analyses resolved subgenus Wenderothia as monophyletic. Subgenus Catodonia needs to be recircumscribed and the relationships between subgenera Canavalia and Maunaloa remain unclear. Canavalia arose during the Miocene with a mean stem age estimate of 13.8Ma and mean crown age estimate of 8.7Ma, and most extant species evolved during the Pleistocene. Several climatic and geological events are chronologically coincident with the divergence of the major clades of Canavalia (glacial/interglacial periods, Andes uplift and the formation of Pebas and post Pebas systems, closure of the Isthmus of Panama, and change in the direction of ocean currents). Ancestral area reconstructions for the early divergence of the genus are equivocal, although, some evidence suggests Canavalia originated in the wet forests of South America and achieved its current pantropical distribution through recent transoceanic dispersal. The evolution of Canavalia is better explained by a series of several processes than by discrete historical events. PMID- 26860336 TI - Effect of Age, Season, Body Condition, and Endocrine Status on Serum Free Cortisol Fraction and Insulin Concentration in Horses. AB - BACKGROUND: Increased free cortisol fraction is associated with insulin dysregulation (ID) in people with Metabolic Syndrome and Cushing's Disease. Free cortisol has not been investigated in equine endocrine disorders. HYPOTHESES: (1) In healthy horses, sex, age, body condition score (BCS), and season impact free cortisol; (2) free cortisol is increased in horses with Pituitary Pars Intermedia Dysfunction (PPID) or Equine Metabolic Syndrome (EMS). ANIMALS: Fifty-seven healthy horses; 40 horses and ponies with PPID (n = 20) or EMS (n = 20). METHODS: Prospective study. Serum collected seasonally from healthy animals and archived serum from PPID and EMS animals was analyzed for insulin, total and free cortisol concentrations, and free cortisol fraction (FCF). Linear mixed models were used to determine effects of age, sex, season, and BCS on hormones in controls. Hormone measurements were compared between disease groups and age- and season matched controls with t-tests. EMS and hyperinsulinemic PPID animals were combined in an ID (hyperinsulinemia) group. RESULTS: Free cortisol concentrations were increased in overweight/obese controls (0.3 +/- 0.1 MUg/dL) compared to lean controls (0.2 +/- 0.1 MUg/dL; P = .017). Mean FCF was significantly higher in animals with PPID (8.8 +/- 5.8 MUg/dL, P = .005) or ID (8.8 +/- 10.2 MUg/dL, P = .039) than controls (5.0 +/- 0.9 MUg/dL), but total cortisol concentrations were similar (P >= .350) (PPID: 4.2 +/- 4.3 MUg/dL; ID: 5.0 +/- 4.5 MUg/dL; controls: 4.6 +/- 1.7 and 5.1 +/- 2.1 MUg/dL). CONCLUSIONS AND CLINICAL IMPORTANCE: Increased FCF is associated with obesity in healthy horses and with ID (hyperinsulinemia) in horses and ponies with endocrine disease. Decreased plasma cortisol-binding capacity could be a component of these endocrine disorders in horses. PMID- 26860340 TI - Equivalent chemotherapy efficacy against leukemia in mice treated with topical vasoconstrictors to prevent cancer therapy side effects. AB - Topically applied vasoconstrictor is a new strategy to prevent oral mucositis and alopecia, two complications of chemotherapy and stem-cell transplant. We sought to determine whether mice treated with topical vasoconstrictor minutes before chemotherapy to suppress L1210 leukemia would develop a vasoconstrictor-induced L1210 cell sanctuary, and with it, significantly worse survival outcomes. B6D2F1 mice received 10(4) mouse L1210 leukemia cells via retro-orbital intravenous injection and were then divided into treatment groups, which included: (i) no further treatment, (ii) a single, sub-curative, intraperitoneal dose of cyclophosphamide (90 ug/gm bw) 24 hr after L1210 cell inoculation, (iii) topical epinephrine (25-400 mM) to clipped dorsal backs 20 min before cyclophosphamide or (iv) orotopical phenylephrine (16-130 mM), epinephrine (10 mM) or norepinephrine (25 mM) 20 min before cyclophosphamide. All mice were then followed until day of death. Differences in median survival time and percent survival between mice receiving cyclophosphamide alone and mice treated with either orotopical phenylephrine, epinephrine or norepinephrine; or topical epinephrine before cyclophosphamide were not significantly different. A discernible leukemia sanctuary was not created by topical vasoconstrictor treatment prior to chemotherapy; there was no significant difference in leukemia progression between untreated mice and those treated with either orotopical or topical vasoconstrictor before chemotherapy. We have opened a Phase I/IIa dose escalation trial to evaluate the safety and efficacy of orotopical phenylephrine in preventing oral mucositis in subjects undergoing hematopoietic stem cell transplant conditioning with cyclophosphamide plus total body irradiation. This could provide a cost-effective and convenient method to prevent oral mucositis. PMID- 26860341 TI - A cross-hospital exploration of nurses' experiences with horizontal violence. AB - AIM: To explore nurses' experiences of horizontal violence (HV) in three diverse non-affiliated organisations within a single city in the USA. BACKGROUND: Horizontal violence, also called workplace bullying or lateral violence, is a long-standing nursing issue. METHOD: Content analysis was used to analyse open format textual responses from 126 registered nurses. RESULTS: A powerful collective story emerged from nurses' shared experiences with HV, describing the characters and the setting in which HV and its consequences exist. Nurses' depictions of HV were consistent despite the different organisational structures of their workplaces suggesting that hospital type is not the explanation for HV, rather the culture of acute care nursing. Nurses want change and asked for tactics to resolve HV within their institutions; some provided specific solutions. CONCLUSION: Nurse managers must continue to address HV by using a variety of known tactics, as well as adopting new evidence-based interventions as they are identified. The anti-bullying message should be disseminated through professional nursing organisations as well as in local health-care establishments. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers need to be the culture champions who hold individuals accountable for HV and foster professionalism through their leadership. PMID- 26860342 TI - Cellular and Molecular Mechanisms of AKI. AB - In this article, we review the current evidence for the cellular and molecular mechanisms of AKI, focusing on epithelial cell pathobiology and related cell-cell interactions, using ischemic AKI as a model. Highlighted are the clinical relevance of cellular and molecular targets that have been investigated in experimental models of ischemic AKI and how such models might be improved to optimize translation into successful clinical trials. In particular, development of more context-specific animal models with greater relevance to human AKI is urgently needed. Comorbidities that could alter patient susceptibility to AKI, such as underlying diabetes, aging, obesity, cancer, and CKD, should also be considered in developing these models. Finally, harmonization between academia and industry for more clinically relevant preclinical testing of potential therapeutic targets and better translational clinical trial design is also needed to achieve the goal of developing effective interventions for AKI. PMID- 26860343 TI - Idiopathic Retroperitoneal Fibrosis. AB - Idiopathic retroperitoneal fibrosis (RPF), reviewed herein, is a rare fibro inflammatory disease that develops around the abdominal aorta and the iliac arteries, and spreads into the adjacent retroperitoneum, where it frequently causes ureteral obstruction and renal failure. The clinical phenotype of RPF is complex, because it can be associated with fibro-inflammatory disorders involving other organs, is considered part of the spectrum of IgG4-related disease, and often arises in patients with other autoimmune conditions. Obstructive uropathy is the most common complication, although other types of renal involvement may occur, including stenosis of the renal arteries and veins, renal atrophy, and different types of associated GN. Environmental and genetic factors contribute to disease susceptibility, whereas the immunopathogenesis of RPF is mediated by different immune cell types that eventually promote fibroblast activation. The diagnosis is made on the basis of computed tomography or magnetic resonance imaging, and positron emission tomography is a useful tool in disease staging and follow-up. Treatment of idiopathic RPF aims at relieving ureteral obstruction and inducing disease regression, and includes the use of glucocorticoids, combined or not with other traditional immunosuppressants. However, biologic therapies such as the B cell-depleting agent rituximab are emerging as potentially efficacious agents in difficult-to-treat cases. PMID- 26860345 TI - Avoiding unnecessary arterial blood sampling in COPD exacerbations: a stab in the right direction. PMID- 26860346 TI - Advanced Sampling for Molecular Simulation is Coming of Age. PMID- 26860344 TI - Neural correlates of cough hypersensitivity in humans: evidence for central sensitisation and dysfunctional inhibitory control. AB - INTRODUCTION: Chronic non-productive coughing is a major complication of pulmonary disease and can also occur in many individuals without identifiable underlying pathology. The common clinical link in patients with cough is an enhanced sensitivity of the respiratory system to stimuli that subsequently evoke excessive coughing. The aetiology of this 'cough hypersensitivity syndrome' is unclear but believed to involve hypersensitivity of the sensory neural pathways that innervate the airways and lungs. METHODS: In the present study, we used functional brain imaging to compare central neural responses to airway stimulation using inhaled capsaicin in healthy people and patients with cough hypersensitivity. RESULTS: Hypersensitivity in response to inhaled capsaicin coincided with elevated neural activity in the midbrain in a region encompassing the nucleus cuneiformis (left: p<0.001; right: p<0.001) and periaqueductal gray (p=0.008) in comparison to normal sensitivity in controls. The enhanced activity noted in the midbrain is similar to that occurring in patients with chronic pain, thus providing empirical evidence to support the notion that cough and pain share neurobiological similarities. Furthermore, patients with cough hypersensitivity displayed difficulty controlling their cough, which manifested as a failure to suppress cough during capsaicin challenge (ie, reduced cough frequency) in controls compared with patients with cough hypersensitivity (p=0.046). Cough suppression was associated with reduced activity in a forebrain network that included the dorsomedial prefrontal and anterior mid-cingulate cortices. Additionally, cough frequency was correlated with activity in the right inferior frontal gyrus (R(2)=0.6, p<0.001) and right anterior insula (R(2)=0.6, p<0.001), regions previously implicated in voluntary cough suppression. CONCLUSIONS: These findings provide insight into the central neurobiology of cough hypersensitivity and suggest that both central amplification of cough sensory inputs and reduced capacity to suppress cough motor behaviours define patients with problematic cough. PMID- 26860351 TI - Combined antibody and DNA detection for early diagnosis of leptospirosis after a disaster. AB - Early diagnosis based on laboratory confirmation is essential for managing leptospirosis. This study investigated the effectiveness of a novel method of detecting leptospirosis that combines measurement of anti-Leptospira antibodies by the microscopic agglutination test (MAT), enzyme-linked immunosorbent assay (ELISA), and immunochromatographic test (ICT) and leptospiral DNA by loop mediated isothermal amplification (LAMP) and real-time PCR in plasma and 2 types of urine pellets. Of 113 suspected cases, 68.1%, 76.1%, and 60.2% were positive by MAT, ELISA, and ICT, respectively. Real-time PCR using DNA purified from urine pellets collected by low-speed centrifugation yielded positive signals for patients in late acute as well as early phase who were positive by LAMP using plasma DNA or urine pellets. Among antibody-negative patients, 9.5% were positive by DNA detection. These findings indicate that the leptospirosis detection rate is increased by combining antibody and DNA detection, providing a new tool for timely diagnosis of infection. PMID- 26860350 TI - Microelectromechanical System-Based Sensing Arrays for Comparative in Vitro Nanotoxicity Assessment at Single Cell and Small Cell-Population Using Electrochemical Impedance Spectroscopy. AB - The traditional in vitro nanotoxicity assessment approaches are conducted on a monolayer of cell culture. However, to study a cell response without interference from the neighbor cells, a single cell study is necessary; especially in cases of neuronal, cancerous, and stem cells, wherein an individual cell's fate is often not explained by the whole cell population. Nonetheless, a single cell does not mimic the actual in vivo environment and lacks important information regarding cell communication with its microenvironment. Both a single cell and a cell population provide important and complementary information about cells' behaviors. In this research, we explored nanotoxicity assessment on a single cell and a small cell population using electrochemical impedance spectroscopy and a microelectromechanical system (MEMS) device. We demonstrated a controlled capture of PC12 cells in different-sized microwells (to capture a different number of cells) using a combined method of surface functionalization and dielectrophoresis. The present approach provides a rapid nanotoxicity response as compared to other conventional approaches. This is the first study, to our knowledge, which demonstrates a comparative response of a single cell and small cell colonies on the same MEMS platform, when exposed to metaloxide nanoparticles. We demonstrated that the microenvironment of a cell is also accountable for cells' behaviors and their responses to nanomaterials. The results of this experimental study open up a new hypothesis to be tested for identifying the role of cell communication in spreading toxicity in a cell population. PMID- 26860352 TI - The importance of matrix-assisted laser desorption ionization-time of flight mass spectrometry for correct identification of Clostridium difficile isolated from chromID C. difficile chromogenic agar. AB - The clinical workflow of using chromogenic agar and matrix-assisted laser desorption ionization time-of-fight mass spectrometry (MALDI-TOF MS) for Clostridium difficile identification was evaluated. The addition of MALDI-TOF MS identification after the chromID C. difficile chromogenic agar culture could significantly improve the diagnostic accuracy of C. difficile. PMID- 26860353 TI - Effects of a multilayered DNA/protamine coating on titanium implants on bone responses. AB - DNA coating on dental titanium (Ti) implants is attracting attention due to its osteogenic properties. The aim of the present study was to evaluate in vitro and in vivo bioactivities of a multilayered DNA/protamine (D/P) coating on Ti implant by simulated body fluid (SBF) immersion experiments and implantation experiments into extracted sockets of rat molars. Two types of DNA, 300 base pair (bp) and 7000 bp fragments, were used. Protamine was initially immobilized onto Ti implants using a tresyl chloride-activated method and DNA and protamine were then alternatively deposited after the immobilization of protamine by a layer-by-layer technique. A multilayered D/P-coating was confirmed by X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy measurements. The deposition of apatite progressed more on the surfaces of multilayered D/P-coated Ti implants than on those of nontreated Ti implants in SBF immersion experiments. Animal implantation experiments showed that multilayered D/P-coated Ti implants provided a significantly higher bone-to-implant (BIC) contact ratio 3 weeks after implantation. No significant difference was observed in the BIC ratio 9 weeks after implantation. The results of the present study demonstrated that a multilayered D/P-coating promoted new bone formation at the early stages of the bone healing process. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1500-1509, 2016. PMID- 26860354 TI - Congenital lobar emphysema concurrent with pneumothorax and pneumomediastinum in a dog. AB - A two-year-old castrated male Pomeranian dog was referred with the chief complaints of coughing and subcutaneous emphysema. On physical examination, the crepitant areas were palpable. When auscultated, the right chest was absent of respiratory sound, while the sound of the opposite side was enhanced. Radiographs presented pneumothorax and pneumomediastinum. On computed tomography, hypoattenuated bulla-like lesion at right middle lung lobe and trapped air in mediastinum were shown. After patient stabilization, surgery for excision of affected lobe was performed. During follow-up period, there were no recurrence and complication on radiographic examination. Based on clinical and pathological findings, the dog was diagnosed as congenital lobar emphysema. PMID- 26860355 TI - Primary T-cell high-grade lymphoma of the feline uterus. AB - A 12-year-old female American shorthair cat presented with a one-month history of hematuria and general lethargy. Abdominal ultrasonography revealed complete thickening of the left uterine wall. At a diagnostic laparotomy, a large mass arising from the left uterine horn was discovered, and ovariohysterectomy was performed. Histological diagnosis revealed a T-cell high-grade lymphoma of the uterus. After the ovariohysterectomy, the patient achieved complete remission and was maintained by combination chemotherapy from 14 days after surgery. However, relapse occurred in the urinary bladder wall on day 287, and the patient died of postrenal acute renal failure on day 310. This is the first report of a feline case of primary uterine lymphoma that was treated with ovariohysterectomy followed by systemic chemotherapy. PMID- 26860356 TI - Factors associated with marketable milk production recovery after treatment of naturally occurring acute coliform mastitis. AB - Milk production loss after recovery from acute coliform mastitis causes major economic losses for dairy industries. Declines in milk production and composition are caused by multiple factors, including cow factors, microorganisms and treatments, but the influence of each factor has not been determined. To investigate risk factors for milk loss after treatment for acute coliform mastitis, multiple logistic regression analyses were conducted in 53 clinical cases. Systemic administration of fluoroquinolone was significantly associated with recovery of marketable milk production. The time to slaughter was significantly shorter in cows with complete loss of quarter milk production than in cows that produced marketable milk. In this study, we identified factors associated with increased risk of milk production loss. PMID- 26860357 TI - Exogenous auxin regulates multi-metabolic network and embryo development, controlling seed secondary dormancy and germination in Nicotiana tabacum L. AB - BACKGROUND: Auxin was recognized as a secondary dormancy phytohormone, controlling seed dormancy and germination. However, the exogenous auxin controlled seed dormancy and germination remain unclear in physiological process and gene network. RESULTS: Tobacco seeds soaked in 1000 mg/l auxin solution showed markedly decreased germination compared with that in low concentration of auxin solutions and ddH2O. Using an electron microscope, observations were made on the seeds which did not unfold properly in comparison to those submerged in ddH2O. The radicle traits measured by WinRHIZO, were found to be also weaker than the other treatment groups. Quantified by ELISA, there was no significant difference found in beta-1,3glucanase activity and abscisic acid (ABA) content between the seeds imbibed in gradient concentration of auxin solution and those soaked in ddH2O. However, gibberellic acid (GA) and auxin contents were significantly higher at the time of exogenous auxin imbibition and were gradually reduced at germination. RNA sequencing (RNA-seq), revealed that the transcriptome of auxin-responsive dormancy seeds were more similar to that of the imbibed seeds when compared with primary dormancy seeds by principal component analysis. The results of gene differential expression analysis revealed that auxin-controlled seed secondary dormancy was associated with flavonol biosynthetic process, gibberellin metabolic process, adenylyl-sulfate reductase activity, thioredoxin activity, glutamate synthase (NADH) activity and chromatin regulation. In addition, auxin-responsive germination responded to ABA, auxin, jasmonic acid (JA) and salicylic acid (SA) mediated signaling pathway (red, far red and blue light), glutathione and methionine (Met) metabolism. CONCLUSIONS: In this study, exogenous auxin-mediated seed secondary dormancy is an environmental model that prevents seed germination in an unfavorable condition. Seeds of which could not imbibe normally, and radicles of which also could not develop normally and emerge. To complete the germination, seeds of which would stimulate more GA synthesis to antagonize the stimulation of exogenous auxin. Exogenous auxin regulates multi-metabolic networks controlling seed secondary dormancy and germination, of which the most important thing was that we found the auxin responsive seed secondary dormancy refers to epigenetic regulation and germination to enhance Met pathway. Therefore, this study uncovers a previously unrecognized transcriptional regulatory networks and physiological development process of seed dormancy and germination with superfluous auxin signal activate. PMID- 26860359 TI - Summer and fall ants have different physiological responses to food macronutrient content. AB - Seasonally, long-lived animals exhibit changes in behavior and physiology in response to shifts in environmental conditions, including food abundance and nutritional quality. Ants are long-lived arthropods that, at the colony level, experience such seasonal shifts in their food resources. Previously we reported summer- and fall-collected ants practiced distinct food collection behavior and nutrient intake regulation strategies in response to variable food protein and carbohydrate content, despite being reared in the lab under identical environmental conditions and dietary regimes. Seasonally distinct responses were observed for both no-choice and choice dietary experiments. Using data from these same experiments, our objective here is to examine colony and individual-level physiological traits, colony mortality and growth, food processing, and worker lipid mass, and how these traits change in response to variable food protein carbohydrate content. For both experiments we found that seasonality per se exerted strong effects on colony and individual level traits. Colonies collected in the summer maintained total worker mass despite high mortality. In contrast, colonies collected in the fall lived longer, and accumulated lipids, including when reared on protein-biased diets. Food macronutrient content had mainly transient effects on physiological responses. Extremes in food carbohydrate content however, elicited a compensatory response in summer worker ants, which processed more protein-biased foods and contained elevated lipid levels. Our study, combined with our previously published work, strongly suggests that underlying physiological phenotypes driving behaviors of summer and fall ants are likely fixed seasonally, and change circannually. PMID- 26860358 TI - Identification of Conserved and Diverse Metabolic Shifts during Rice Grain Development. AB - Seed development dedicates to reserve synthesis and accumulation and uncovering its genetic and biochemical mechanisms has been a major research focus. Although proteomic and transcriptomic analyses revealed dynamic changes of genes and enzymes involved, the information regarding concomitant metabolic changes is missing. Here we investigated the dynamic metabolic changes along the rice grain development of two japonica and two indica cultivars using non-targeted metabolomics approach, in which we successfully identified 214 metabolites. Statistical analyses revealed both cultivar and developmental stage dependent metabolic changes in rice grains. Generally, the stage specific metabolic kinetics corresponded well to the physiological status of the developing grains, and metabolic changes in developing rice grain are similar to those of dicot Arabidopsis and tomato at reserve accumulation stage but are different from those of dicots at seed desiccation stage. The remarkable difference in metabolite abundances between japonica and indica rice grain was observed at the reserve accumulation stage. Metabolite-metabolite correlation analysis uncovered potential new pathways for several metabolites. Taken together, this study uncovered both conserved and diverse development associated metabolic kinetics of rice grains, which facilitates further study to explore fundamental questions regarding the evolution of seed metabolic capabilities as well as their potential applications in crop improvement. PMID- 26860360 TI - The carbapenem-resistant Enterobacteriaceae threat is growing: NDM-1 epidemic at a training hospital in Turkey. AB - BACKGROUND: Recently, new carbapenemases in Enterobacteriaceae strains and non fermentative gram-negative bacilli have been reported. The New Delhi metallo-beta lactamase-1 (NDM-1) is a major problem around the world. The purpose of this article is to address the NDM-1 Klebsiella pneumoniae epidemic detected in eight cases in our hospital. METHODS: Bacteria identified in this epidemic were from patients already admitted to the intensive care unit of the Sakarya University Training and Research Hospital during efforts toward establishment of infection surveillance and control program. Antimicrobial susceptibility testing of strains was performed using the VITEK 2 system (bioMerieux, France), E-test gradient strips (bioMerieux, France), and the disc diffusion test. For the metallo-beta lactamase activity, the combined disc diffusion test and modified Hodge test as phenotypic tests were performed. To identify the resistance gene, the Xpert Carba R kit (Cepheid Inc., USA) and an in-house multiplex polymerase chain reaction (PCR) method designed for five common carbapenemase genes (IMP, VIM, KPC, NDM-1, and OXA-48) were employed. The clonal relationship of these strains was explored by the repetitive PCR (rep-PCR, DiversiLab System, bioMerieux, France) method. RESULTS: During the December 2014 to March 2015 period, NDM-1 positive K. pneumoniae strains were detected in eight patients. All of these strains were found to produce NDM-1, while two of them also revealed the presence of OXA-48. The rep-PCR results reveal a clonal proximity of 95 % for six of the eight strains. CONCLUSIONS: Our findings suggest the tendency of NDM-1-producing strains to spread in our country as well. A carbapenem-resistant K. pneumoniae threat may pose a great risk to our country. It is clear that more comprehensive infection control precautions should be implemented in our hospitals. PMID- 26860361 TI - Evaluating early response of cervical cancer under concurrent chemo-radiotherapy by intravoxel incoherent motion MR imaging. AB - BACKGROUND: Intravoxel incoherent motion (IVIM) MR imaging has been applied in researches of various diseases, however its potential in cervical cancer patients has not been fully explored. The purpose of this study was to investigate the feasibility of IVIM MR imaging to monitor early treatment response in patients receiving concurrent chemo-radiotherapy (CCRT) for advanced cervical cancers. METHODS: Twenty-one patients receiving CCRT for advanced cervical cancer were prospectively enrolled. MR examinations including IVIM imaging (with 14 b values, 0 ~ 1000 s/mm(2)) were performed at 4 time points: 1-week prior to, 2-week and 4 week during, as well as immediately post CCRT (within 1 week). The apparent diffusion coefficient (ADC) maps were derived from the mono-exponential model, while the diffusion coefficient (D), perfusion fraction (f) and pseudo-diffusion coefficient (D*) maps were calculated from the bi-exponential model. Dynamic changes of ADC, D, f and D* in cervical cancers were investigated as early surrogate markers for treatment response. RESULTS: ADC and D values increased throughout the CCRT course. Both f and D* increased in the first 2 to 3 weeks of CCRT and started to decrease around 4 weeks of CCRT. Significant increase of f value was observed from prior to CCRT (f 1 = 0.12 +/- 0.52) to two-week during CCRT (f2 = 0.20 +/- 0.90, p = 0.002). CONCLUSIONS: IVIM MR imaging has the potential in monitoring early tumor response induced by CCRT in patients with cervical cancers. PMID- 26860362 TI - Evaluation of the effects of implementing an electronic early warning score system: protocol for a stepped wedge study. AB - BACKGROUND: An Early Warning Score is a clinical risk score based upon vital signs intended to aid recognition of patients in need of urgent medical attention. The use of an escalation of care policy based upon an Early Warning Score is mandated as the standard of practice in British hospitals. Electronic systems for recording vital sign observations and Early Warning Score calculation offer theoretical benefits over paper-based systems. However, the evidence for their clinical benefit is limited. Previous studies have shown inconsistent results. The majority have employed a "before and after" study design, which may be strongly confounded by simultaneously occurring events. This study aims to examine how the implementation of an electronic early warning score system, System for Notification and Documentation (SEND), affects the recognition of clinical deterioration occurring in hospitalised adult patients. METHODS: This study is a non-randomised stepped wedge evaluation carried out across the four hospitals of the Oxford University Hospitals NHS Trust, comparing charting on paper and charting using SEND. We assume that more frequent monitoring of acutely ill patients is associated with better recognition of patient deterioration. The primary outcome measure is the time between a patient's first observations set with an Early Warning Score above the alerting threshold and their subsequent set of observations. Secondary outcome measures are in-hospital mortality, cardiac arrest and Intensive Care admission rates, hospital length of stay and system usability measured using the System Usability Scale. We will also measure Intensive Care length of stay, Intensive Care mortality, Acute Physiology and Chronic Health Evaluation (APACHE) II acute physiology score on admission, to examine whether the introduction of SEND has any effect on Intensive Care-related outcomes. DISCUSSION: The development of this protocol has been informed by guidance from the Agency for Healthcare Research and Quality (AHRQ) Health Information Technology Evaluation Toolkit and Delone and McLeans's Model of Information System Success. Our chosen trial design, a stepped wedge study, is well suited to the study of a phased roll out. The choice of primary endpoint is challenging. We have selected the time from the first triggering observation set to the subsequent observation set. This has the benefit of being easy to measure on both paper and electronic charting and having a straightforward interpretation. We have collected qualitative measures of system quality via a user questionnaire and organisational descriptors to help readers understand the context in which SEND has been implemented. PMID- 26860363 TI - Breaking the germ line-soma barrier. PMID- 26860364 TI - Translation: Start upstream to relieve stress. PMID- 26860367 TI - Vacuum template synthesis of multifunctional nanotubes with tailored nanostructured walls. AB - A three-step vacuum procedure for the fabrication of vertical TiO2 and ZnO nanotubes with three dimensional walls is presented. The method combines physical vapor deposition of small-molecules, plasma enhanced chemical vapor deposition of inorganic functional thin films and layers and a post-annealing process in vacuum in order to remove the organic template. As a result, an ample variety of inorganic nanotubes are made with tunable length, hole dimensions and shapes and tailored wall composition, microstructure, porosity and structure. The fabrication of multishell nanotubes combining different semiconducting oxides and metal nanoparticles is as well explored. This method provides a feasible and reproducible route for the fabrication of high density arrays of vertically alligned nanotubes on processable substrates. The emptying mechanism and microstructure of the nanotubes have been elucidated through SEM, STEM, HAADF STEM tomography and energy dispersive X-ray spectroscopy. In this article, as a proof of concept, it is presented the straightforward integration of ZnO nanotubes as photoanode in a photovoltaic cell and as a photonic oxygen gas sensor. PMID- 26860366 TI - The Indispensable Role of Cyclin-Dependent Kinase 1 in Skeletal Development. AB - Skeletal development is tightly regulated through the processes of chondrocyte proliferation and differentiation. Although the involvement of transcription and growth factors on the regulation of skeletal development has been extensively studied, the role of cell cycle regulatory proteins in this process remains elusive. To date, through cell-specific loss-of-function experiments in vivo, no cell cycle regulatory proteins have yet been conclusively shown to regulate skeletal development. Here, we demonstrate that cyclin-dependent kinase 1 (Cdk1) regulates skeletal development based on chondrocyte-specific loss-of-function experiments performed in a mouse model. Cdk1 is highly expressed in columnar proliferative chondrocytes and is greatly downregulated upon differentiation into hypertrophic chondrocytes. Cdk1 is essential for proper chondrocyte proliferation and deletion of Cdk1 resulted in accelerated differentiation of chondrocytes. In vitro and ex vivo analyses revealed that Cdk1 is an essential cell cycle regulatory protein for parathyroid hormone-related peptide (PTHrP) signaling pathway, which is critical to chondrocyte proliferation and differentiation. These results demonstrate that Cdk1 functions as a molecular switch from proliferation to hypertrophic differentiation of chondrocytes and thus is indispensable for skeletal development. Given the availability of inhibitors of Cdk1 activity, our results could provide insight for the treatment of diseases involving abnormal chondrocyte proliferation, such as osteoarthritis. PMID- 26860365 TI - Dynamic stem cell states: naive to primed pluripotency in rodents and humans. AB - The molecular mechanisms and signalling pathways that regulate the in vitro preservation of distinct pluripotent stem cell configurations, and their induction in somatic cells by direct reprogramming, constitute a highly exciting area of research. In this Review, we integrate recent discoveries related to isolating unique naive and primed pluripotent stem cell states with altered functional and molecular characteristics, and from different species. We provide an overview of the pathways underlying pluripotent state transitions and interconversion in vitro and in vivo. We conclude by highlighting unresolved key questions, future directions and potential novel applications of such dynamic pluripotent cell states. PMID- 26860368 TI - Fine-tuning of CD8(+) T-cell effector functions by targeting the 2B4-CD48 interaction. AB - Polyfunctionality and cytotoxic activity dictate CD8(+) T-cell efficacy in the eradication of infected and malignant cells. The induction of these effector functions depends on the specific interaction between the T-cell receptor (TCR) and its cognate peptide-MHC class I complex, in addition to signals provided by co-stimulatory or co-inhibitory receptors, which can further regulate these functions. Among these receptors, the role of 2B4 is contested, as it has been described as either co-stimulatory or co-inhibitory in modulating T-cell functions. We therefore combined functional, transcriptional and epigenetic approaches to further characterize the impact of disrupting the interaction of 2B4 with its ligand CD48, on the activity of human effector CD8(+) T-cell clones. In this setting, we show that the 2B4-CD48 axis is involved in the fine-tuning of CD8(+) T-cell effector function upon antigenic stimulation. Blocking this interaction resulted in reduced CD8(+) T-cell clone-mediated cytolytic activity, together with a subtle drop in the expression of genes involved in effector function regulation. Our results also imply a variable contribution of the 2B4 CD48 interaction to the modulation of CD8(+) T-cell functional properties, potentially linked to intrinsic levels of T-bet expression and TCR avidity. The present study thus provides further insights into the role of the 2B4-CD48 interaction in the fine regulation of CD8(+) T-cell effector function upon antigenic stimulation. PMID- 26860369 TI - The molecular mechanisms of TLR-signaling cooperation in cytokine regulation. AB - Innate immune cells recognize pathogens through pattern recognition receptors (PRRs), and activation of PRRs induces downstream signaling pathways to mount appropriate immune responses. Pathogens usually carry multiple ligands, which can simultaneously activate multiple PRRs. The cooperation of multiple PRRs and consequential crosstalk between their downstream pathways could enhance cytokine expression, which is required for effective immune responses. On the other hand, immune over-activation could also harm the host if immune homeostasis is not restored. Therefore, it is important to understand the mechanisms of PRR cooperation during an infection. As the best characterized PRRs, Toll-like receptors (TLRs) have an important role in pathogen recognition, and crosstalk among TLRs is common. In this review, we provide an update on the recent findings on the mechanisms of TLR cooperation. We summarize the known mechanisms and provide a future perspective on TLR crosstalk study, with a caution against the use of multiple TLR ligands as adjuvants in therapeutic strategies. PMID- 26860371 TI - Hospital cornerstones are crumbling. PMID- 26860370 TI - Linking the T cell receptor to the single cell transcriptome in antigen-specific human T cells. AB - Heterogeneity of T cells is a hallmark of a successful adaptive immune response, harnessing the vast diversity of antigen-specific T cells into a coordinated evolution of effector and memory outcomes. The T cell receptor (TCR) repertoire is highly diverse to account for the highly heterogeneous antigenic world. During the response to a virus multiple individual clones of antigen specific CD8+ (Ag specific) T cells can be identified against a single epitope and multiple epitopes are recognised. Advances in single-cell technologies have provided the potential to study Ag-specific T cell heterogeneity at both surface phenotype and transcriptome levels, thereby allowing investigation of the diversity within the same apparent sub-population. We propose a new method (VDJPuzzle) to reconstruct the native TCRalphabeta from single cell RNA-seq data of Ag-specific T cells and then to link these with the gene expression profile of individual cells. We applied this method using rare Ag-specific T cells isolated from peripheral blood of a subject who cleared hepatitis C virus infection. We successfully reconstructed productive TCRalphabeta in 56 of a total of 63 cells (89%), with double alpha and double beta in 18, and 7% respectively, and double TCRalphabeta in 2 cells. The method was validated via standard single cell PCR sequencing of the TCR. We demonstrate that single-cell transcriptome analysis can successfully distinguish Ag-specific T cell populations sorted directly from resting memory cells in peripheral blood and sorted after ex vivo stimulation. This approach allows a detailed analysis of the TCR diversity and its relationship with the transcriptional profile of different clones. PMID- 26860372 TI - [Not Available]. PMID- 26860373 TI - [Not Available]. PMID- 26860374 TI - [Not Available]. PMID- 26860375 TI - [Not Available]. PMID- 26860377 TI - [Clinical research on elderly]. PMID- 26860378 TI - [Limited basis for changing the goals for blood pressure treatment]. PMID- 26860379 TI - [Surveying complaints after colorectal surgery]. PMID- 26860380 TI - [Basic course--only for advanced students?]. PMID- 26860381 TI - [Not Available]. PMID- 26860382 TI - Investigation of suspected chronic fatigue syndrome/myalgic encephalopathy. AB - BACKGROUND: Chronic fatigue is a frequently occurring problem in both the primary and specialist health services. The Department of Neurology at Haukeland University Hospital has established a standard assessment for patients referred with suspected CFS/ME. This study reports diagnoses and findings upon assessment, and considers the benefit of supplementary examinations. MATERIAL AND METHOD: Diagnoses and findings from examinations of 365 patients assessed for suspected CFS/ME are retrospectively reported. RESULTS: A total of 48 patients (13.2%) were diagnosed with CFS/ME, while a further 18 patients (4.9%) were diagnosed with post-infectious fatigue. Mental and behavioural disorders were diagnosed in 169 patients (46.3%), and these represented by far the largest group. Serious, but unrecognised somatic illness was discovered in two patients, while changes of uncertain significance were identified by MRI and lumbar puncture in a few patients. INTERPRETATION: Fatigue is a frequently occurring symptom in the population. Thorough somatic and psychiatric investigation is necessary before referral to the specialist health services. Mental disorders and reactions to life crises are common and important differential diagnoses for CFS/ME. Long waiting times in the specialist health services may result in delayed diagnosis for these patients. PMID- 26860383 TI - Extravasation injuries. AB - It is common for an intravascular catheter to be inserted to administer various types of therapy. Extravasation occurs frequently, and in the most severe cases plastic surgeons are often summoned to assess the extent of the injury and the possibility for reconstruction. The Department of Plastic and Reconstructive Surgery at Oslo University Hospital assesses approximately 15 severe cases of this type each year. PMID- 26860384 TI - [A man in his 20s with abdominal pain and heart murmurs]. PMID- 26860386 TI - [Not Available]. PMID- 26860388 TI - [Not Available]. PMID- 26860385 TI - [Orphan drugs]. PMID- 26860389 TI - [Not Available]. PMID- 26860390 TI - [Not Available]. PMID- 26860392 TI - [Not Available]. PMID- 26860391 TI - [Not Available]. PMID- 26860393 TI - Luminescence- and nanoparticle-mediated increase of light absorption by photoreceptor cells: Converting UV light to visible light. AB - We developed new optic devices - singly-doped luminescence glasses and nanoparticle-coated lenses that convert UV light to visible light - for improvement of visual system functions. Tb(3+) or Eu(3+) singly-doped borate glasses or CdS-quantum dot (CdS-QD) coated lenses efficiently convert UV light to 542 nm or 613 nm wavelength narrow-band green or red light, or wide-spectrum white light, and thereby provide extra visible light to the eye. In zebrafish (wild-type larvae and adult control animals, retinal degeneration mutants, and light-induced photoreceptor cell degeneration models), the use of Tb(3+) or Eu(3+) doped luminescence glass or CdS-QD coated glass lenses provide additional visible light to the rod and cone photoreceptor cells, and thereby improve the visual system functions. The data provide proof-of-concept for the future development of optic devices for improvement of visual system functions in patients who suffer from photoreceptor cell degeneration or related retinal diseases. PMID- 26860394 TI - The role of Xpert MTB/RIF in diagnosing pulmonary tuberculosis in post-mortem tissues. AB - The extent to which the Xpert MTB/RIF (Gene Xpert) contributes to tuberculosis (TB) diagnosis in samples other than sputum and cerebrospinal fluid remains uncertain. We aimed to assess the role of Xpert MTB/RIF for detecting M. tuberculosis in post-mortem tissues. We conducted a study among 30 complete diagnostic autopsies (CDA) performed at the Maputo Central Hospital (Mozambique). Lung tissues were screened for TB in all cases. In addition other tissues were tested when compatible lesions were identified in the histological exam. We used in-house real time PCR and LAMP assays to confirm the presence of M. tuberculosis DNA. The diagnosis of tuberculosis at death was established based on microbiological and histopathological results. Eight out of 30 cases (26.7%) were diagnosed of tuberculosis. Xpert had a sensitivity to detect TB in lung tissue of 87.5% (95% CI 47.3-99.7) and a specificity of 95.7% (95% CI: 78.1-99.9). In-house DNA amplification methods and Xpert showed 93.6% concordance for lung tissue and 100% concordance for brain and liver tissues. The final cause of death was attributable to tuberculosis in four cases. Xpert MTB/RIF may represent a valuable, easy-to perform technique for post-mortem TB diagnosis. PMID- 26860395 TI - Improvement of Mitochondria Extract from Saccharomyces cerevisiae Characterization in Shotgun Proteomics Using Sheathless Capillary Electrophoresis Coupled to Tandem Mass Spectrometry. AB - In this work, we describe the characterization of a quantity-limited sample (100 ng) of yeast mitochondria by shotgun bottom-up proteomics. Sample characterization was carried out by sheathless capillary electrophoresis, equipped with a high sensitivity porous tip and coupled to tandem mass spectrometry (CESI-MS-MS) and concomitantly with a state-of-art nano flow liquid chromatography coupled to a similar mass spectrometry (MS) system (nanoLC-MS-MS). With single injections, both nanoLC-MS-MS and CESI-MS-MS 60 min-long separation experiments allowed us to identify 271 proteins (976 unique peptides) and 300 proteins (1,765 unique peptides) respectively, demonstrating a significant specificity and complementarity in identification depending on the physicochemical separation employed. Such complementary, maximizing the number of analytes detected, presents a powerful tool to deepen a biological sample's proteomic characterization. A comprehensive study of the specificity provided by each separating technique was also performed using the different properties of the identified peptides: molecular weight, mass-to-charge ratio (m/z), isoelectric point (pI), sequence coverage or MS-MS spectral quality enabled to determine the contribution of each separation. For example, CESI-MS-MS enables to identify larger peptides and eases the detection of those having extreme pI without impairing spectral quality. The addition of peptides, and therefore proteins identified by both techniques allowed us to increase significantly the sequence coverages and then the confidence of characterization. In this study, we also demonstrated that the two yeast enolase isoenzymes were both characterized in the CESI-MS-MS data set. The observation of discriminant proteotypic peptides is facilitated when a high number of precursors with high-quality MS-MS spectra are generated. PMID- 26860396 TI - QbD-Driven Development and Validation of a Bioanalytical LC-MS Method for Quantification of Fluoxetine in Human Plasma. AB - The current studies describe the Quality by Design (QbD)-based development and validation of a LC-MS-MS method for quantification of fluoxetine in human plasma using fluoxetine-D5 as an internal standard (IS). Solid-phase extraction was employed for sample preparation, and linearity was observed for drug concentrations ranging between 2 and 30 ng/mL. Systematic optimization of the method was carried out by employing Box-Behnken design with mobile phase flow rate (X1), pH (X2) and mobile phase composition (X3) as the method variables, followed by evaluating retention time (Rt) (Y1) and peak area (Y2) as the responses. The optimization studies revealed reduction in the variability associated with the method variables for improving the method robustness. Validation studies of the developed method revealed good linearity, accuracy, precision, selectivity and sensitivity of fluoxetine in human plasma. Stability studies performed in human plasma through freeze-thaw, bench-top, short-term and long-term cycles, and autosampler stability revealed lack of any change in the percent recovery of the drug. In a nutshell, the developed method demonstrated satisfactory results for analysis of fluoxetine in human plasma with plausible utility in pharmacokinetic and bioequivalence studies. PMID- 26860397 TI - Development and Validation of a Novel Stability-Indicating RP-HPLC Method for the Simultaneous Determination of Related Substances of Ketoprofen and Omeprazole in Combined Capsule Dosage Form. AB - A novel, simple, sensitive, selective and reproducible stability-indicating high performance liquid chromatographic method was developed for the quantitative determination of degradation products and process-related impurities of ketoprofen (KET) and omeprazole (OMZ) in combined oral solid dosage form. Chromatographic separation was achieved on a Phenomenex Luna C18 (2) column (150 * 4.6 mm, 5 MUm) under gradient elution by using a binary mixture of potassium dihydrogen phosphate buffer and acetonitrile at a flow rate of 0.8 mL/min. Chromatogram was monitored at 233 nm for KET impurities and at 305 nm for OMZ impurities using a dual wavelength UV detector. Resolution for KET and OMZ and 14 impurities was found to be >1.5 for any pair of components. Typical retention behaviors of impurities at various pH values were depicted graphically. To prove the stability-indicating power of the method, the drug product was subjected to hydrolytic, oxidative, photolytic, humidity and thermal stress conditions as per ICH. The developed method was validated according to the current ICH guidelines for specificity, limit of detection, limit of quantification, linearity, accuracy, precision, ruggedness and robustness. PMID- 26860398 TI - Prevalence of Exercise-Induced Bronchoconstriction Measured by Standardized Testing in Healthy College Athletes. AB - BACKGROUND: Exercise-induced bronchoconstriction (EIB) can lead to long-term respiratory illness and even death. EIB prevalence rates are both high and variable in college athletes. Prevalence rates may be underestimated due to ineffective testing and screening. The purpose of this study was to investigate the prevalence of EIB in college athletes by a standardized EIB test that can be used on many college campuses. In addition, we assessed the usefulness of self reporting EIB/asthma (1) history, (2) symptoms, and (3) respiratory medication obtained from a simple screening questionnaire for predicting an EIB-positive athlete. METHODS: A standardized EIB test and self-report questionnaire were administered to college athletes on 10 different sports teams. Information collected included pulmonary function (spirometry), expired gas analysis (maximal oxygen uptake), CO2 production, minute ventilation, EIB/asthma history, current symptoms, and medication use. RESULTS: Results showed that 34 of 80 athletes (42.5%) were EIB-positive by standardized exercise testing. The majority (76.5 and 58.8%) of the 34 athletes who tested positive self-reported a negative history or no symptoms, respectively. Also, 79.4% of the athletes who tested positive for EIB reported not using a respiratory medication. There were no significant differences in a positive EIB test when assessing interactions for history (P = .93), current symptoms (P = .12), or respiratory medication use (P = .66). CONCLUSIONS: A high proportion of college athletes tested positive for EIB when using a standardized test. Positive history, current symptoms of EIB/asthma, and respiratory medication use were not predictive of a positive test. Many EIB positive athletes are not using a respiratory medication. More work is needed to develop an effective screening tool and improve education for EIB in college athletes. PMID- 26860399 TI - Tracheostomy Tube Type and Inner Cannula Selection Impact Pressure and Resistance to Air Flow. AB - BACKGROUND: Advancements in tracheostomy tube design now provide clinicians with a range of options to facilitate communication for individuals receiving ventilator assistance through a cuffed tube. Little is known about the impact of these modern design features on resistance to air flow. METHODS: We undertook a bench model test to measure pressure-flow characteristics and resistance of a range of tubes of similar outer diameter, including those enabling subglottic suction and speech. A constant inspiratory +/- expiratory air flow was generated at increasing flows up to 150 L/min through each tube (with or without optional, mandatory, or interchangeable inner cannula). Driving pressures were measured, and resistance was calculated (cm H2O/L/s). RESULTS: Pressures changed with increasing flow (P < .001) and tube type (P < .001), with differing patterns of pressure change according to the type of tube (P < .001) and direction of air flow. The single-lumen reference tube encountered the lowest inspiratory and expiratory pressures compared with all double-lumen tubes (P < .001); placement of an optional inner cannula increased bidirectional tube resistance by a factor of 3. For a tube with interchangeable inner cannulas, the type of cannula altered pressure and resistance differently (P < .001); the speech cannula in particular amplified pressure-flow changes and increased tube resistance by more than a factor of 4. CONCLUSIONS: Tracheostomy tube type and inner cannula selection imposed differing pressures and resistance to air flow during inspiration and expiration. These differences may be important when selecting airway equipment or when setting parameters for monitoring, particularly for patients receiving supported ventilation or during the weaning process. PMID- 26860400 TI - High-Risk Smoking Behaviors and Barriers to Smoking Cessation Among Homeless Individuals. AB - BACKGROUND: Although tobacco practices and the effects of tobacco use among the general American population are well described, minimal data exist regarding tobacco use and barriers to smoking cessation among homeless individuals. METHODS: Anonymous, voluntary surveys based on a previously implemented instrument were completed by 100 smoking individuals residing at a homeless shelter. These surveys assessed high-risk smoking behaviors and respondents' perceived barriers to long-term smoking cessation. RESULTS: Ninety percent of study participants reported engaging in at least one of the high-risk tobacco practices. Nicotine replacement therapy was perceived by respondents to be the most desired form of smoking cessation aid. Excessive stress with use of tobacco smoking to alleviate stress and anxiety was the most significant self-perceived barrier to smoking cessation. CONCLUSIONS: High-risk tobacco practices are remarkably common among smoking homeless individuals. Despite literature consistently showing that non-nicotine tobacco cessation pharmacotherapies (varenicline, buproprion) have higher smoking cessation rates, nicotine replacement monotherapy was perceived as more valuable by survey respondents. Although lack of financial resources was expected to be the biggest barrier to successful cessation, social stressors and the use of smoking to cope with homelessness were perceived as a greater obstacle in this cohort. Given the paucity of data on the long-term effects of the high-risk tobacco behaviors reported by these homeless smokers, this study highlights the need for further investigations regarding tobacco use and tobacco cessation in this vulnerable population. PMID- 26860401 TI - Letter to the Editor in reference to: Controversies in the management of sudden sensorineural hearing loss (SSNHL): an evidence-based review. PMID- 26860402 TI - Establishing well-being after hip fracture: a systematic review and meta synthesis. AB - PURPOSE: This study aimed to identify, appraise, aggregate and synthesize findings of experiences of self-confidence and well-being after hip fracture. METHOD: The systematic review followed the Joanna Briggs Institute (JBI) guidelines. A three-step literature search strategy was followed. Included studies were critically appraised using the JBI critical appraisal tool. Data were analyzed into a meta-summary and a meta-synthesis using a hermeneutic approach. RESULTS: Twenty-nine studies were included in the analysis. The category "balancing a new life" was illustrated through older people's "adaptations", "adjustments" and "worries". The second category "striving for interaction with new life possibilities" was built on experiences of "supportive interaction", "missing interaction" and "obstacles". The abstraction of the categories into the meta-synthesis "establishing well-being described the process of older people gradually coming to terms with new life conditions". It was a process of building confidence through cooperation with staff. CONCLUSIONS: Experiences of well-being were possible after hip fracture. Self-confidence enhanced adaptations and adjustments. Older people strived for an active everyday life where they had a sense of identity. Health professionals can facilitate the establishing of well-being through supportive interaction being aware of vulnerabilities and possibilities. This study provides information that may help in the development of interventions taking into account what is meaningful for older people. Implications for Rehabilitation Both staff and significant others play a significant role during rehabilitation after hip fracture and can give rise to both well-being and suffering. During rehabilitation, experiences of self efficacy can be important as they support progress and adaptation towards a new way of living. After hip fracture, older people may have worries and can experience a diversity of obstacles. A sensitivity towards these experiences by health care professionals can be a support for older people striving to establish well-being after hip fracture. To enhance functional ability and experiences of independency, it may be important to consider what it is about activities that are meaningful in the lives of older people after a hip fracture. PMID- 26860403 TI - Triple Tendon Transfer for Correction of Foot Deformity in Common Peroneal Nerve Palsy. AB - BACKGROUND: Anterior transfer of posterior tibial tendon (PTT) is the most common technique to correct foot drop in patients with common peroneal nerve palsy. It does not address the loss of toe extension or "toe drop." This may affect the gait pattern, and patients may not tolerate it. Described here is a technique that addresses toe drop associated with common peroneal nerve palsy. METHOD: A new technique of tendon transfer using the PTT, flexor hallucis longus (FHL) tendon, and flexor digitorum longus (FDL) tendon was performed on 15 patients (13 males and 2 females) with complete common peroneal nerve palsy from 2009 to 2013. Minimum follow-up was 12 months (range, 12-50 months). The mean age was 37 years (range, 20-52 years). RESULTS: Based on the evaluation criteria of Carayon et al, the postoperative results for foot drop correction were excellent in 9 (60%), good in 5 (33%), and moderate in 1 (7%), and the mean active range of motion of the ankle was 46 degrees. Postoperative extension evaluation of the toes was excellent in 7 (47%), good in 5 (33%), and moderate in 3 (20%). CONCLUSION: Releasing and transferring of FDL and FHL to the toe extensors along with the anterior transfer of the PTT neutralized the deforming forces and allowed for active toe extension while strengthening ankle dorsiflexion. Movahedi Tendon Transfer was a reliable method to achieve a balanced foot and toe dorsiflexion for complete common peroneal nerve palsy. LEVEL OF EVIDENCE: Level IV, retrospective case series. PMID- 26860404 TI - Pushing the limits of catalytic C-H amination in polyoxygenated cyclobutanes. AB - A synthetic route to a new class of conformationally constrained iminosugars based on a 5-azaspiro[3.4]octane skeleton has been developed by way of Rh(ii) catalyzed C(sp(3))-H amination. The pivotal stereocontrolled formation of the quaternary C-N bond by insertion into the C-H bonds of the cyclobutane ring was explored with a series of polyoxygenated substrates. In addition to anticipated regioselective issues induced by the high density of activated alpha-ethereal C-H bonds, this systematic study showed that cyclobutane C-H bonds were, in general, poorly reactive towards catalytic C-H amination. This was demonstrated inter alia by the unexpected formation of a oxathiazonane derivative, which constitutes a very rare example of the formation of a 9-membered ring by way of catalyzed C(sp(3))-H amination. A complete stereocontrol could be however achieved by activating the key insertion position as an allylic C-H bond in combination with reducing the electron density at the undesired C-H insertion sites by using electron-withdrawing protecting groups. Preliminary biological evaluations of the synthesized spiro-iminosugars were performed, which led to the identification of a new class of correctors of the defective F508del-CFTR gating involved in cystic fibrosis. PMID- 26860405 TI - Targeting hepatic TRAF1-ASK1 signaling to improve inflammation, insulin resistance, and hepatic steatosis. AB - BACKGROUND & AIMS: Tumor necrosis factor receptor-associated factor 1 (TRAF1) is an important adapter protein that is largely implicated in molecular events regulating immunity/inflammation and cell death. Although inflammation is closely related to and forms a vicious circle with insulin dysfunction and hepatic lipid accumulation, the role of TRAF1 in hepatic steatosis and the related metabolic disorders remains unclear. METHODS: The participation of TRAF1 in the initiation and progression of hepatic steatosis was evaluated in high fat diet (HFD)-induced and genetic obesity. Mice with global TRAF1 knockout or liver-specific TRAF1 overexpression were employed to investigate the role of TRAF1 in insulin resistance, inflammation, and hepatic steatosis based on various phenotypic examinations. Molecular mechanisms underlying TRAF1-regulated hepatic steatosis were further explored in vivo and in vitro. RESULTS: TRAF1 expression was significantly upregulated in the livers of NAFLD patients and obese mice and in palmitate-treated hepatocytes. In response to HFD administration or in ob/ob mice, TRAF1 deficiency was hepatoprotective, whereas the overexpression of TRAF1 in hepatocytes contributed to the pathological development of insulin resistance, inflammatory response and hepatic steatosis. Mechanistically, hepatocyte TRAF1 promotes hepatic steatosis through enhancing the activation of ASK1-mediated P38/JNK cascades, as evidenced by the fact that ASK1 inhibition abolished the exacerbated effect of TRAF1 on insulin dysfunction, inflammation, and hepatic lipid accumulation. CONCLUSIONS: TRAF1 functions as a positive regulator of insulin resistance, inflammation, and hepatic steatosis dependent on the activation of ASK1-P38/JNK axis. PMID- 26860406 TI - Emergency Room Visits by Uninsured Child and Adult Residents in Ontario, Canada: What Diagnoses, Severity and Visit Disposition Reveal About the Impact of Being Uninsured. AB - Canadian immigrants can be without health insurance for many reasons but limited data exists regarding uninsured health outcomes. Uninsured Canadian residents were identified in the National Ambulatory Care Reporting System for all visits to emergency departments in Ontario, Canada between 2002/3 and 2010/11 (N = 44,489,750). Frequencies for main diagnoses, severity (triage), and visit disposition were compared. Ambulatory care sensitive conditions were identified in a 10 % subsample. The uninsured (N = 140,730; 0.32 %) were more likely to be diagnosed with mental health (insured: 3.48 %; uninsured: 10.47 %) or obstetric problems (insured: 2.69 %; uninsured: 5.56 %), be triaged into the two most severe categories (insured: 11.2 %; uninsured 15.6 %), leave untreated (insured: 3.1 %; uninsured: 5.4 %), or die (insured: 2.8 %; uninsured: 3.7 %). More ACSC visits were made by uninsured children and youth. Insurance status is associated with more serious health status on arrival to emergency departments and more negative visit outcomes. PMID- 26860408 TI - [Options and limitations of heart rate measurement and analysis of heart rate variability by mobile devices: A systematic review]. AB - BACKGROUND: Heart rate (HR) and heart rate variability (HRV) have been established in the last few years as a non-invasive method for recording the demands on the cardiovascular system. The development enables us today to measure the interbeat intervals with different technologies for calculating HR and HRV. MATERIALS AND METHODS: This review is based on a systematic literature search in PubMed for validity of different measurement techniques and their pros and cons for the measurement of HR and the analysis of HRV. RESULTS: Measurement equipment for recording of interbeat intervals should have a high storage capacity and a sampling rate of 1000 Hz ideally. The quality criteria of freedom of feedback (small, little disruptive), robustness and a non-invasive measurement (e. g. freeze-electrodes or sensors) have to be fulfilled. In addition to the Holter ECG, several portable heart rate watch and chest belt systems provide adequate validity and good applicability. DISCUSSION: The Holter ECG is still the gold standard for the measurement of NN intervals and for the analysis of HRV. Modern heart rate watches show a good correlation with the conformance of freedom from discomfort, robustness and non-invasive measurement and are a good alternative due to the lower disturbance of test persons. PMID- 26860409 TI - [Importance of mechanical assist devices in acute circulatory arrest]. AB - Mechanical assist devices are indicated for hemodynamic stabilization in acute circulatory arrest if conventional means of cardiopulmonary resuscitation are unable to re-establish adequate organ perfusion. Their temporary use facilitates further diagnostic and therapeutic options in selected patients, e.g. coronary angiography followed by revascularization.External thorax compression devices allow sufficient cardiac massage in case of preclinical or in-hospital circulatory arrest, especially under complex transfer conditions. These devices perform standardized thorax compressions at a rate of 80-100 per minute. Invasive mechanical support devices are used in the catheter laboratory or in the intensive care unit. Axial turbine pumps, e.g. the Impella, continuously pump blood from the left ventricle into the aortic root. The Impella can also provide right ventricle support by pumping blood from the vena cava into the pulmonary artery. So-called emergency systems or ECMO devices consist of a centrifugal pump and a membrane oxygenator allowing complete takeover of cardiac and pulmonary functions. Withdrawing blood from the right atrium and vena cava, oxygenated blood is returned to the abdominal aorta. Isolated centrifugal pumps provide left heart support without an oxygenator after transseptal insertion of a venous cannula into the left atrium.Mechanical assist devices are indicated for acute organ protection and hemodynamic stabilization for diagnostic and therapeutic measures as well as bridge to myocardial recovery. Future technical developments and better insights into the pathophysiology of mechanical circulatory support will broaden the spectrum of indications of such devices in acute circulatory arrest. PMID- 26860410 TI - Conditioned Medium Derived from Neural Progenitor Cells Induces Long-term Post ischemic Neuroprotection, Sustained Neurological Recovery, Neurogenesis, and Angiogenesis. AB - Adult neural progenitor cells (NPCs) induce post-ischemic long-term neuroprotection and brain remodeling by releasing of survival- and plasticity promoting mediators. To evaluate whether secreted factors may mimic neuroprotective and restorative effects of NPCs, we exposed male C57BL6 mice to focal cerebral ischemia and intravenously applied conditioned medium (CM) derived from subventricular zone NPCs. CM dose-dependently reduced infarct volume and brain leukocyte infiltration after 48 h when delivered up to 12 h after focal cerebral ischemia. Neuroprotection persisted in the post-acute stroke phase yielding enhanced neurological recovery that lasted throughout the 28-day observation period. Increased Bcl-2, phosphorylated Akt and phosphorylated STAT-3 abundance, and reduced caspase-3 activity and Bax abundance were noted in ischemic brains of CM-treated mice at 48 h post-stroke, indicative of enhanced cell survival signaling. Long-term neuroprotection was associated with increased brain glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF) concentrations at 28 days resulting in increased neurogenesis and angiogenesis. The observation that NPC-derived CM induces sustained neuroprotection and neurological recovery suggests that cell transplantation may be dispensable when secreted factors are instead administered. PMID- 26860411 TI - Differential Expression and Significance of Circulating microRNAs in Cerebrospinal Fluid of Acute Encephalitis Patients Infected with Japanese Encephalitis Virus. AB - Changes in circulating microRNAs (miRNAs) in the cerebrospinal fluid (CSF) have been associated with different neurological diseases. Here, we presented results of a pilot study aimed at determining the feasibility of detecting miRNAs in the CSF of Japanese Encephalitis virus (JEV) infected individuals with acute encephalitis syndrome (AES). We demonstrated the circulating miRNA profile in CSF of acute encephalitis patients infected with JEV. Using a quantitative real-time PCR-based miRNA array, we examined the level of 87 miRNAs expressed in human exosomes isolated from CSF. Subsequently, correlation between cytokine level and miRNAs expression in CSF samples was examined. In this study, we identified and validated the upregulated expression of three miRNAs, miR-21-5p, miR-150-5p, and miR-342-3p that were specifically circulated in CSF of acute encephalitis patients infected with JEV. CSF miR-21-5p, miR-150-5p, and miR-342-3p expressions were also elevated in infected mice brain. However, the expression pattern of these miRNAs differed in neuronal cells, microglial cells, and the exosome derived from JEV-infected cell culture supernatant. Interestingly, neuronal cells infected with vaccine strain (SA-14-14) did not lead to any upregulation of these three miRNAs. Further, miR-150-5p expression was found to be negatively correlated(r = -0.5279, p = 0.016) with TNFalpha level. Pathway analysis of putative target genes of these miRNAs indicated involvement of TGF-beta, NGF, axon guidance, and MAPK signaling pathways in JEV/AES patients. This study for the first time represents the circulating miRNA in CSF of AES patients and identified the upregulated miRNAs in JEV-infected patients and offers the basis for future investigation. PMID- 26860412 TI - Caffeine Reverts Memory But Not Mood Impairment in a Depression-Prone Mouse Strain with Up-Regulated Adenosine A2A Receptor in Hippocampal Glutamate Synapses. AB - Caffeine prophylactically prevents mood and memory impairments through adenosine A2A receptor (A2AR) antagonism. A2AR antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. HM displayed higher immobility in the tail suspension and forced swimming tests, greater anxiety in the elevated plus maze, and poorer memory performance (modified Y-maze and object recognition). HM also had reduced density of synaptic (synaptophysin, SNAP-25), namely, glutamatergic (vGluT1; -22 +/- 7 %) and GABAergic (vGAT; -23 +/- 8 %) markers in the hippocampus. HM displayed higher A2AR density (72 +/- 6 %) in hippocampal synapses, an enhanced facilitation of hippocampal glutamate release by the A2AR agonist, CGS21680 (30 nM), and a larger LTP amplitude (54 +/- 8 % vs. 21 +/- 5 % in controls) that was restored to control levels (30 +/- 10 %) by the A2AR antagonist, SCH58261 (50 nM). Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A2AR controlling synaptic glutamatergic function. PMID- 26860413 TI - Rheumatoid factor isotypes in relation to antibodies against citrullinated peptides and carbamylated proteins before the onset of rheumatoid arthritis. AB - BACKGROUND: The presence of rheumatoid factor (RF), anti-carbamylated protein antibodies (anti-CarP) and antibodies against citrullinated protein and peptides (ACPA) precedes the onset of symptoms of rheumatoid arthritis (RA) by several years. Relationships between the development of these antibodies are not obvious. METHODS: Three isotypes [immunoglobulin A (IgA), IgG and IgM) of RF were analysed in 321 pre-symptomatic individuals who provided 598 samples collected a median of 6.2 (interquartile range 7.2) years before the onset of symptoms, and in 492 population control subjects. All samples were donated to the Biobank of Northern Sweden. RF isotypes were analysed using the EliA system (Phadia GmbH, Freiburg, Germany) with 96 % specificity according to receiver operating characteristic curves. Ten ACPA specificities were analysed using the ImmunoCAP ISAC system, and anti-CCP2 and anti-CarP antibodies were evaluated using enzyme-linked immunosorbent assays. RESULTS: The frequencies of RF isotypes in pre-symptomatic individuals were significantly increased compared with control subjects (p < 0.0001). In samples collected >=15 years before the onset of symptoms, the IgA-RF isotype was significantly more prevalent than the most frequent ACPAs. Combinations of IgM- and IgA-RF isotypes with ACPA specificities [alpha-enolase (CEP-1/Eno5-21)], fibrinogen (Fib)beta36-52, Fibalpha580-600, filaggrin (CCP 1/Fil307-324) and anti-CCP2 antibodies were associated with a significantly shorter time to onset of symptoms (p < 0.001-0.05). Using conditional inference tree analysis, anti-CCP2 in combination with anti-filaggrin antibodies gave the highest probability, 97.5 %, for disease development. CONCLUSIONS: RF isotypes predicted the development of RA, particularly in combination with ACPA, anti-CCP2 or anti-CarP antibodies. The highest probability for disease development was the presence of anti-CCP2 and anti-filaggrin antibodies. PMID- 26860414 TI - Diverse photoreceptors and light responses in plants. PMID- 26860415 TI - Lactate and glucose measurement in subepidermal tissue using minimally invasive microperfusion needle. AB - Knowing the concentrations of biological substances can help ascertain physiological and pathological states. In the present study, a minimally invasive microperfusion needle was developed for measuring the concentrations of biological substances in subepidermal tissue. The microperfusion needle has a flow channel with a perforated membrane through which biological substances from subepidermal tissue are extracted. Since this device uses a thin steel acupuncture needle as the base substrate, it has sufficient rigidity for insertion through the skin. The efficacy of the needle was examined by measuring lactate and glucose concentrations in mice. Lactate was injected intraperitoneally, and changes in lactate concentrations in subepidermal tissue over time were measured using the device. Lactate concentrations of blood were also measured as a reference. Lactate was successfully collected using the microperfusion needle, and the lactate concentration of perfused saline was significantly correlated with blood lactate concentration. Glucose solution was administered orally, and the glucose concentration of perfused saline was also correlated with blood glucose concentration. The newly developed microperfusion needle can be used for minimally invasive monitoring of the concentrations of biological substances. PMID- 26860416 TI - Comparison and optimization of ten phage encoded serine integrases for genome engineering in Saccharomyces cerevisiae. AB - BACKGROUND: Phage-encoded serine integrases, such as phiC31 integrase, are widely used for genome engineering but have not been optimized for use in Saccharomyces cerevisiae although this organism is a widely used organism in biotechnology. RESULTS: The activities of derivatives of fourteen serine integrases that either possess or lack a nuclear localization signal were compared using a standardized recombinase mediated cassette exchange reaction. The relative activities of these integrases in S. cerevisiae and in mammalian cells suggested that the major determinant of the activity of an integrase is the enzyme itself and not the cell in which it is working. We used an inducible promoter to show that six integrases were toxic as judged by their effects upon the proliferative ability of transformed yeast. We show that in general the active phage-encoded serine integrases were an order of magnitude more efficient in promoting genome integration reactions than a simple homologous recombination. CONCLUSIONS: The results of our study allow us to identify the integrases of the phage phiBT1, TP901 ~ nls, R4, Bxb1, MR11, A118, phiK38, phiC31 ~ nls, Wbeta and SPBC ~ nls as active in S. cerevisiae and indicate that vertebrate cells are more restricted than yeast in terms of which integrases are active. PMID- 26860417 TI - [Seroprevalence of varicella-zoster virus antibodies after the recent introduction of the universal childhood immunisation schedule in the Community of Madrid]. AB - BACKGROUND AND OBJECTIVE: In November 2006, the Community of Madrid included the chickenpox vaccine into the immunisation schedule for children from 15 months of age. This was withdrawn in January 2014. Seroprevalence of antibodies to the virus is estimated after the first 2-3 years from the inclusion of the vaccine, and as well as its evolution since 1999. MATERIAL AND METHOD: A cross-sectional study was conducted on the target population consisting of residents in the Community of Madrid between 2 and 60 years of age. Measurement of IgG antibodies was performed using an ELISA technique. Seroprevalence was estimated according to sociodemographic characteristics using multiple logistic regressions. The results are compared with previous surveys. Also, the seroprevalence and geometric mean of the antibody according immunisation status and history of the disease are presented. The confidence level used is 95%. RESULTS: A total of 4,378 subjects were included, with a response rate of 69%. The estimated seroprevalence was 95.3% (95% CI: 94.6% - 95.9%). Over 90% of children from the age of 10 have antibodies. The seroprevalence was higher in people with less education. The seroprevalence of immunity vaccine exceeds 90% in the first year after vaccination, but in the second year decreased to 82.6% (95% CI 56.0 - 94.7). Significant differences, attributable to universal vaccination, were found compared to previous surveys. DISCUSSION: Continued surveillance is needed in order to assess the impact of the withdrawal of the recommendation to vaccinate at 15 months. PMID- 26860418 TI - [Infective endocarditis in adult patients with congenital heart disease. Experience from a reference centre]. AB - INTRODUCTION: A growing number of patients with congenital heart disease (CHD) will reach adulthood. Infective endocarditis (IE) is a major complication in this population. The aim of this study was to describe the features of IE in adults with CHD treated in a reference centre. METHODS: A retrospective review was performed on a cohort of patients over 16 years of age with CHD who presented with IE (defined by the modified Duke criteria) between 1996 and 2014. Only the first episode from each patient was considered for the descriptive analysis. RESULTS: IE was observed in 27 patients. The median age at diagnosis of IE was 27.7 years, and 63% were male. Comorbidity was low (median Charlson index was 0). IE was mostly community-acquired (78%). The most frequent CHD were ventricular septal defect (33%). A repair was performed in 48% of patients, and 19% received palliative treatment. Forty-one percent of patients had some type of prosthesis. A residual defect was observed in 81%. The IE was detected in the right side of 44% of the patients. The most frequent aetiological agents were viridans group streptococci (41%) and Staphylococcus epidermidis (30%). Surgery was required to treat IE in 37% of patients. There were five re-infections and three relapses. Two patients died, both as a result of recurrence. CONCLUSIONS: IE in adults with CHD occurred in young patients, and almost all of them carried some prosthetic material or a residual defect. The IE is frequently right-sided. Although surgical treatment was required in many cases, mortality was low, except in the case of relapses. PMID- 26860419 TI - Hyperpigmented Plaques of the Alar Crease: An Unusual Presentation of Acanthosis Nigricans. AB - Although acanthosis nigricans of the posterior neck and intertriginous areas is common, acanthosis nigricans of the supra-alar creases is rare. We present the case of an obese 16-year-old African American boy with hyperpigmented plaques along the supra-alar creases of his nose. Clinicians should be aware of this rare manifestation, because newly diagnosed acanthosis nigricans should prompt examination for insulin resistance. PMID- 26860420 TI - The influence of intraoperative resection control modalities on survival following gross total resection of glioblastoma. AB - The purpose of the present study is to analyze the impact of intraoperative resection control modalities on overall survival (OS) and progression-free survival (PFS) following gross total resection (GTR) of glioblastoma. We analyzed data of 76 glioblastoma patients (30f, mean age 57.4 +/- 11.6 years) operated at our institution between 2009 and 2012. Patients were only included if GTR was achieved as judged by early postoperative high-field MRI. Intraoperative technical resection control modalities comprised intraoperative ultrasound (ioUS, n = 48), intraoperative low-field MRI (ioMRI, n = 22), and a control group without either modality (n = 11). The primary endpoint of our study was OS, and the secondary endpoint was PFS-both analyzed in Kaplan-Meier plots and Cox proportional hazards models. Median OS in all 76 glioblastoma patients after GTR was 20.4 months (95 % confidence interval (CI) 18.5-29.0)-median OS in patients where GTR was achieved using ioUS was prolonged (21.9 months) compared to those without ioUS usage (18.8 months). A multiple Cox model adjusting for age, preop Karnofsky performance status, tumor volume, and the use of 5-aminolevulinic acid showed a beneficial effect of ioUS use, and the estimated hazard ratio was 0.63 (95 % CI 0.31-1.2, p = 0.18) in favor of ioUS, however not reaching statistical significance. A similar effect was found for PFS (hazard ratio 0.59, p = 0.072). GTR of glioblastoma performed with ioUS guidance was associated with prolonged OS and PFS. IoUS should be compared to other resection control devices in larger patient cohorts. PMID- 26860421 TI - High urinary albumin/creatinine ratio at admission predicts poor functional outcome in patients with acute ischaemic stroke. AB - AIM: Albuminuria and a low estimated glomerular filtration rate (eGFR) are widely recognized indices of kidney dysfunction and have been linked to cardiovascular events, including stroke. We evaluated albuminuria, measured using the urinary albumin/creatinine ratio (UACR), and the eGFR in the acute phase of ischaemic stroke, and investigated the clinical characteristics of ischaemic stroke patients with and those without kidney dysfunction. METHODS: The study included 422 consecutive patients admitted between June 2010 and May 2012. General blood and urine examinations were performed at admission. Kidney dysfunction was defined as a low eGFR (<60 mL/min per 1.73 m2 ), high albuminuria (>=30 mg/g creatinine), or both. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and the modified Rankin scale (mRS) at discharge. A poor outcome was defined as a mRS score of 3-5 or death. The impacts of the eGFR and UACR on outcomes at discharge were evaluated using multiple logistic regression analysis. RESULTS: Kidney dysfunction was diagnosed in 278 of the 422 patients (65.9%). The eGFR was significantly lower and UACR was significantly higher in patients with a poor outcome than in those with a good outcome. In multivariate analyses performed after adjusting for confounding factors, UACR >31.2 mg/g creatinine (OR, 2.58; 95% CI, 1.52-4.43; P = 0.0005) was independently associated with a poor outcome, while a low eGFR was not associated. CONCLUSIONS: A high UACR at admission may predict a poor outcome at discharge in patients with acute ischaemic stroke. PMID- 26860423 TI - Recovery of gold from waste electrical and electronic equipment (WEEE) using ammonium persulfate. AB - This paper presents a novel methodology to recover gold from waste electrical and electronic equipment (WEEE) using ammonium persulfate ((NH4)2S2O8). Gold was recovered as a fine coating using substrate oxidation without shredding or grinding process. The WEEE sample was characterized giving values of Au: 1.05g/kg, Fe: 86.00g/kg, Ni: 73.64g/kg, Cu: 26.65g/kg. The effect of (NH4)2S2O8 concentration (0.22-1.10M), oxygen (0.0-1.4L/min) and L/S ratio (10-30mL/g) on the main responses (substrate oxidation and Au recovery) was investigated implementing response surface methodology with numerical optimization. A quadratic model was developed and quantities greater than 98% of Au were recovered. The findings presented suggest that, optimized quantities of ammonium persulfate in aqueous highly oxygenated media could be used to extract superficial gold from WEEE. PMID- 26860424 TI - Characterizing the biotransformation of sulfur-containing wastes in simulated landfill reactors. AB - Landfills that accept municipal solid waste (MSW) in the U.S. may also accept a number of sulfur-containing wastes including residues from coal or MSW combustion, and construction and demolition (C&D) waste. Under anaerobic conditions that dominate landfills, microbially mediated processes can convert sulfate to hydrogen sulfide (H2S). The presence of H2S in landfill gas is problematic for several reasons including its low odor threshold, human toxicity, and corrosive nature. The objective of this study was to develop and demonstrate a laboratory-scale reactor method to measure the H2S production potential of a range of sulfur-containing wastes. The H2S production potential was measured in 8 L reactors that were filled with a mixture of the target waste, newsprint as a source of organic carbon required for microbial sulfate reduction, and leachate from decomposed residential MSW as an inoculum. Reactors were operated with and without N2 sparging through the reactors, which was designed to reduce H2S accumulation and toxicity. Both H2S and CH4 yields were consistently higher in reactors that were sparged with N2 although the magnitude of the effect varied. The laboratory-measured first order decay rate constants for H2S and CH4 production were used to estimate constants that were applicable in landfills. The estimated constants ranged from 0.11yr(-1) for C&D fines to 0.38yr(-1) for a mixed fly ash and bottom ash from MSW combustion. PMID- 26860422 TI - Outer Membrane Protein Folding and Topology from a Computational Transfer Free Energy Scale. AB - Knowledge of the transfer free energy of amino acids from aqueous solution to a lipid bilayer is essential for understanding membrane protein folding and for predicting membrane protein structure. Here we report a computational approach that can calculate the folding free energy of the transmembrane region of outer membrane beta-barrel proteins (OMPs) by combining an empirical energy function with a reduced discrete state space model. We quantitatively analyzed the transfer free energies of 20 amino acid residues at the center of the lipid bilayer of OmpLA. Our results are in excellent agreement with the experimentally derived hydrophobicity scales. We further exhaustively calculated the transfer free energies of 20 amino acids at all positions in the TM region of OmpLA. We found that the asymmetry of the Gram-negative bacterial outer membrane as well as the TM residues of an OMP determine its functional fold in vivo. Our results suggest that the folding process of an OMP is driven by the lipid-facing residues in its hydrophobic core, and its NC-IN topology is determined by the differential stabilities of OMPs in the asymmetrical outer membrane. The folding free energy is further reduced by lipid A and assisted by general depth-dependent cooperativities that exist between polar and ionizable residues. Moreover, context-dependency of transfer free energies at specific positions in OmpLA predict regions important for protein function as well as structural anomalies. Our computational approach is fast, efficient and applicable to any OMP. PMID- 26860425 TI - Biotic and abiotic dynamics of a high solid-state anaerobic digestion box-type container system. AB - A solid-state anaerobic digestion box-type container system for biomethane production was observed in 12 three-week batch fermentations. Reactor performance was monitored using physico-chemical analysis and the methanogenic community was identified using ANAEROCHIP-microarrays and quantitative PCR. A resilient community was found in all batches, despite variations in inoculum to substrate ratio, feedstock quality, and fluctuating reactor conditions. The consortia were dominated by mixotrophic Methanosarcina that were accompanied by hydrogenotrophic Methanobacterium, Methanoculleus, and Methanocorpusculum. The relationship between biotic and abiotic variables was investigated using bivariate correlation analysis and univariate analysis of variance. High amounts of biogas were produced in batches with high copy numbers of Methanosarcina. High copy numbers of Methanocorpusculum and extensive percolation, however, were found to negatively correlate with biogas production. Supporting these findings, a negative correlation was detected between Methanocorpusculum and Methanosarcina. Based on these results, this study suggests Methanosarcina as an indicator for well-functioning reactor performance. PMID- 26860426 TI - Partial oxidation of sewage sludge briquettes in a updraft fixed bed. AB - The fixed bed reaction of sewage sludge briquettes was investigated to evaluate the potential applications to gasification, combustion, or production of biochar as soil ameliorator. The reaction had two distinctive stages: ignition propagation and char oxidation. The ignition front of the sludge briquettes propagated at a lower speed, which significantly increased the stoichiometric ratio of overall combustion reaction and peak temperatures. The ignition front also had irregular shapes due to the channeling effects. During the char oxidation stage, the sludge ash agglomerated because of the slow reaction rate and increased CO2 formation. Because of low energy content in the product gas, the large briquettes were not favorable for syngas production. In addition, the low burning rates and ash agglomeration could cause problems in the operation of a grate-type furnace for combustion. However, the char accumulated above the ignition front had similar properties with that from pyrolysis under inert atmosphere. Therefore, the fixed bed reaction under partial oxidation conditions can be applied to produce biochar as soil ameliorator from the sludge briquettes without external heat supply. PMID- 26860429 TI - A passenger reduces sleepy driver's activation in the right prefrontal cortex: A laboratory study using near-infrared spectroscopy. AB - The present study aimed to examine how a passenger affects the sleepiness effect (awake vs. sleepy) on an individual's prefrontal activation during a simulated driving-game task using a wireless portable near-infrared spectroscopy (NIRS) device. Participants drove from start to goal along default routes either solely (no-passenger group) or with a friend sitting beside him/her as a passenger (with passenger group). Sleepiness level was assessed by a five-item scale questionnaire. In the no-passenger group, there were no performance and activation differences between the sleepy and awake participants. In the with passenger group, by contrast, the sleepy participants showed more errors and lower activations in their right prefrontal cortex than the awake participants. These results suggest that a passenger has little effect on awake participants, but may weaken the sleepy participants' vigilance and/or their cognitive abilities of action control. Practically, the present study demonstrates that NIRS may provide us a new possibility to monitor and examine the driver's mental states in the brain. PMID- 26860427 TI - Identification and functional analysis of a bacteriocin, pyocin S6, with ribonuclease activity from a Pseudomonas aeruginosa cystic fibrosis clinical isolate. AB - S-type pyocins are bacteriocins produced by Pseudomonas aeruginosa isolates to antagonize or kill other strains of the same species. They have a modular organization comprising a receptor-binding domain recognizing a surface constituent of the target bacterium, a domain for translocation through the periplasm, and a killing or toxic domain with DNase, tRNase, or pore-forming activity. Pyocins S2, S3, S4, and S5 recognize TonB-dependent ferri-siderophore receptors in the outer membrane. We here describe a new nuclease bacteriocin, pyocin S6, encoded in the genome of a P. aeruginosa cystic fibrosis (CF) clinical isolate, CF_PA39. Similarly to pyocins S1 and S2, the S6 toxin-immunity gene tandem was recruited to the genomic region encoding exotoxin A. The pyocin S6 receptor-binding and translocation domains are identical to those of pyocin S1, whereas the killing domain is similar to the 16S ribonuclease domain of Escherichia coli colicin E3. The cytotoxic activity was abolished in pyocin S6 forms with a mutation in the colicin E3-equivalent catalytic motif. The CF_PA39 S6 immunity gene displays a higher expression level than the gene encoding the killing protein, the latter being only detected when bacteria are grown under iron-limiting conditions. In the S1-pyocinogenic strain P. aeruginosa ATCC 25324 and pyocin S2 producer P. aeruginosa PAO1, a remnant of the pyocin S6 killing domain and an intact S6-type immunity gene are located downstream of their respective pyocin operons. Strain PAO1 is insensitive for pyocin S6, and its S6 type immunity gene provides protection against pyocin S6 activity. Purified pyocin S6 inhibits one-fifth of 110 P. aeruginosa CF clinical isolates tested, showing clearer inhibition zones when the target cells are grown under iron limitation. In this panel, about half of the CF clinical isolates were found to host the S6 genes. The pyocin S6 locus is also present in the genome of some non CF clinical isolates. PMID- 26860430 TI - The effects of goal variation on adult physical activity behaviour. AB - The purposes of this study were to examine the effects of varying levels of goals on increasing daily steps and the frequency of goal achievement among middle-aged adults. Ninety-six adults participated in a randomised control study. Participants were randomly assigned to five different step goal groups: (1) Easy (n = 19), (2) Medium (n = 19), (3) Difficult (n = 19), (4) Do-your-best (n = 19), and (5) No goal (n = 20) based on previous research. The participants wore a pedometer and were asked to reach a pre-established goal during the experimental period. In order to examine the effectiveness of the goal difficulty, (a) an average number of steps taken by different goal conditions and (b) the number of days meeting the assigned goal were tested. A one-way ANCOVA revealed significant step count differences among goal groups. Post hoc analyses indicated that the change in step count in both the Medium and Difficult goal groups was significantly greater than the remaining groups. However, there was no significant difference between the medium and difficult goal conditions. In addition, a one-way ANOVA indicated that there were no significant differences in the frequency of goal achievement among the Easy, Medium, and Difficult goal groups. Results suggest that when promoting physical activity through increasing step counts, researchers and clinicians should design goals that are specific and challenging. PMID- 26860431 TI - The misuse of Cyproheptadine: a non-communicable disease risk behaviour in Kinshasa population, Democratic Republic of Congo. AB - BACKGROUND: Obesity is one of the main risk factors of non-communicable diseases (NCDs) worldwide, especially in sub-Saharan Africa. The use of Cyproheptadine increases body weight and the risk of becoming obese. The aim of this study is to determine the prevalence of Cyproheptadine misuse in the Kinshasa population and to describe its characteristics. METHODS: A cross-sectional study was conducted in two town sectors of Kinshasa, Democratic Republic of Congo (DRC), over a 4 month period (May 2011 to August 2011). Data from 499 participants, aged between 13 and 55 years were collected and analyzed. Mean and standard deviation were used for quantitative variables and frequency and percentage for categorical variables. In order to determine the relationship between socio-demographic status and Cyproheptadine use the Chi-square test was conducted. Student's t-test was used to compare means age of Cyproheptadine users and non-users. Logistic regression was used to determine predictors of Cyproheptadine use. A p-value of <0.05 was considered statistically significant. RESULTS: Overall, 499 participants were enrolled (352 females, 147 males, mean age +/- standard deviation 24.9 +/- 9.7 years) in the study. The majority of the study participants (72.9 %) had used Cyproheptadine as an appetite stimulant. Females were 11 times more likely to use Cryproheptadine (OR = 11.9; 95 % CI: 7.1-20.1) than males. People aged between 36 and 55 were three times less likely to use Cryproheptadine (OR = 0.3; 95 % CI: 0.2-0.8) compared to teenagers. More than half of the participants (69.0 %) declared to take daily Cyproheptadine. Half of the study participants (50.0 %) used Cyproheptadine for more than a year and also declared to combine it with Dexamethasone (87.6 %). CONCLUSION: This study shows that the Kinshasa population is significantly misusing Cyproheptadine and is highly exposed to its risk, including obesity. PMID- 26860432 TI - Erratum: Spatial genomic heterogeneity in diffuse intrinsic pontine and midline high-grade glioma: implications for diagnostic biopsy and targeted therapeutics. AB - Through inadvertent oversight of the authors, the paper failed to acknowledge funding support from Genome Canada. The Acknowledgement section should include the text: "This work was supported by the Canadian Centre for Computational Genomics (C3G), part of the Genome Innovation Network (GIN), funded by Genome Canada through Genome Quebec and Ontario Genomics". PMID- 26860433 TI - First molecular evidence of Coxiella burnetii in patients with atypical pneumonia, India. PMID- 26860434 TI - Effectiveness of an Activity Tracker- and Internet-Based Adaptive Walking Program for Adults: A Randomized Controlled Trial. AB - BACKGROUND: The benefits of physical activity are well documented, but scalable programs to promote activity are needed. Interventions that assign tailored and dynamically adjusting goals could effect significant increases in physical activity but have not yet been implemented at scale. OBJECTIVE: Our aim was to examine the effectiveness of an open access, Internet-based walking program that assigns daily step goals tailored to each participant. METHODS: A two-arm, pragmatic randomized controlled trial compared the intervention to no treatment. Participants were recruited from a workplace setting and randomized to a no treatment control (n=133) or to treatment (n=132). Treatment participants received a free wireless activity tracker and enrolled in the walking program, Walkadoo. Assessments were fully automated: activity tracker recorded primary outcomes (steps) without intervention by the participant or investigators. The two arms were compared on change in steps per day from baseline to follow-up (after 6 weeks of treatment) using a two-tailed independent samples t test. RESULTS: Participants (N=265) were 66.0% (175/265) female with an average age of 39.9 years. Over half of the participants (142/265, 53.6%) were sedentary (<5000 steps/day) and 44.9% (119/265) were low to somewhat active (5000-9999 steps/day). The intervention group significantly increased their steps by 970 steps/day over control (P<.001), with treatment effects observed in sedentary (P=.04) and low-to somewhat active (P=.004) participants alike. CONCLUSIONS: The program is effective in increasing daily steps. Participants benefited from the program regardless of their initial activity level. A tailored, adaptive approach using wireless activity trackers is realistically implementable and scalable. TRIAL REGISTRATION: Clinicaltrials.gov NCT02229409, https://clinicaltrials.gov/ct2/show/NCT02229409 (Archived by WebCite at http://www.webcitation.org/6eiWCvBYe). PMID- 26860435 TI - A review of allergoid immunotherapy: is cat allergy a suitable target? AB - To modify the course of allergy, different types of specific allergen immunotherapy have been developed such as sublingual immunotherapy and subcutaneous immunotherapy with native allergens or subcutaneous immunotherapy with polymerized allergoids. However, the optimal specific immunotherapy, especially for cat allergy, remains undetermined. Few studies investigating immunotherapy in cat allergy have been published, and the risk of serious adverse reactions and systemic reactions has often been an important issue. Monomeric allergoids have lower allergenic potential while their immunogenicity remains constant, resulting in excellent safety with notable efficacy. Specific immunotherapy with monomeric allergoids could, therefore, be of high value, especially in cat allergy as well as other types of allergy, and bring relief to a great community of patients. PMID- 26860436 TI - In Quality We Trust; but Quality of Life or Quality of Care? AB - The ESRD program provides medical care to a diverse and medically complex patient population. The care for the ESRD patient population has become increasingly benchmarked with process of care measures. These measures include dialysis adequacy, anemia, nutrition, and vascular access outcomes. These process-related dialysis measures may not improve the care of the individual patient as care relates to the individual's goals and values. There is also evidence that these process measures may not be causally related to quality of life, hospitalization, and survival. The adoption of patient-reported outcomes may shift the balance toward more patient-centered care. However, the extent to which mandated measures of health-related quality of life and patient satisfaction result in improved outcomes remains unclear. PMID- 26860437 TI - A Mapping Between Structural and Functional Brain Networks. AB - The relationship between structural and functional brain networks is still highly debated. Most previous studies have used a single functional imaging modality to analyze this relationship. In this work, we use multimodal data, from functional MRI, magnetoencephalography, and diffusion tensor imaging, and assume that there exists a mapping between the connectivity matrices of the resting-state functional and structural networks. We investigate this mapping employing group averaged as well as individual data. We indeed find a significantly high goodness of fit level for this structure-function mapping. Our analysis suggests that a functional connection is shaped by all walks up to the diameter in the structural network in both modality cases. When analyzing the inverse mapping, from function to structure, longer walks in the functional network also seem to possess minor influence on the structural connection strengths. Even though similar overall properties for the structure-function mapping are found for different functional modalities, our results indicate that the structure-function relationship is modality dependent. PMID- 26860438 TI - Contextual fear conditioning depresses infralimbic excitability. AB - Patients with posttraumatic stress disorder (PTSD) show hypo-active ventromedial prefrontal cortices (vmPFC) that correlate with their impaired ability to discriminate between safe and dangerous contexts and cues. Previously, we found that auditory fear conditioning depresses the excitability of neurons populating the homologous structure in rodents, the infralimbic cortex (IL). However, it is undetermined if IL depression was mediated by the cued or contextual information. The objective of this study was to examine whether contextual information was sufficient to depress IL neuronal excitability. After exposing rats to context alone, pseudoconditioning, or contextual fear conditioning, we used whole-cell current-clamp recordings to examine the excitability of IL neurons in prefrontal brain slices. We found that contextual fear conditioning reduced IL neuronal firing in response to depolarizing current steps. In addition, neurons from contextual fear conditioned animals showed increased slow afterhyperpolarization potentials (sAHPs). Moreover, the observed changes in IL excitability correlated with contextual fear expression, suggesting that IL depression may contribute to the encoding of contextual fear. PMID- 26860439 TI - Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer. AB - In DNA from prostate tumors, methylation patterns in gene promoter regions can be a biomarker for disease progression. It remains unclear whether methylation patterns in benign prostate tissue--prior to malignant transformation--may provide similar prognostic information. To determine whether early methylation events predict prostate cancer outcomes, we evaluated histologically benign prostate specimens from 353 men who eventually developed prostate cancer and received "definitive" treatment [radical prostatectomy (58%) or radiation therapy (42%)]. Cases were drawn from a large hospital-based cohort of men with benign prostate biopsy specimens collected between 1990 and 2002. Risk of disease progression associated with methylation was estimated using time-to-event analyses. Average follow-up was over 5 years; biochemical recurrence (BCR) occurred in 91 cases (26%). In White men, methylation of the APC gene was associated with increased risk of BCR, even after adjusting for standard clinical risk factors for prostate cancer progression (adjusted hazard ratio (aHR) = 2.26; 95%CI 1.23-4.16). APC methylation was most strongly associated with a significant increased risk of BCR in White men with low prostate specific antigen at cohort entry (HR = 3.66; 95%CI 1.51-8.85). In additional stratified analyses, we found that methylation of the RARB gene significantly increased risk of BCR in African American cases who demonstrated methylation of at least one of the other four genes under study (HR = 3.80; 95%CI 1.07-13.53). These findings may have implications in the early identification of aggressive prostate cancer as well as reducing unnecessary medical procedures and emotional distress for men who present with markers of indolent disease. PMID- 26860441 TI - Flipping the model for access to patient records. PMID- 26860440 TI - Factors Associated With Parents' Perceptions of Their Infants' Oral Health Care. AB - INTRODUCTION: Parents have an important role ensuring their infants receive oral and medical health care. Their decisions affect the well-being of their children. METHODS: This study used data collected from a longitudinal, prospective study with the aim of developing and validating a caries risk assessment tool. The objectives of this study are to (a) compare parents' perceptions of how well they do in taking care of the infants' teeth and/or gums versus how well they do in taking care of the infants' medical health and (b) determine factors associated with parental perceptions of how well they do in taking care of the infants' teeth and/or gums. RESULTS: A total of 1323 parent/infant pairs were enrolled in the study at Duke University, Indiana University, and the University of Iowa. Through a survey, 283 (21%) of the parents perceived they did an excellent job of both taking care of both the infant's oral and medical health, while 861 (65%) perceived the care of their infant's medical health was better than their care of the teeth and/or gums. In the multivariable model, parents who perceived they provided excellent/very good/good care for the infants' teeth and/or gums were more likely to brush the infant's teeth daily, use toothpaste daily, clean inside the infant's mouth and/or gums daily, and not let the infant have something other than water after brushing and prior to bedtime. Also, those with infants having Medicaid or State Insurance, parents not eating sugary snacks frequently, and parents getting dental checkups at least annually were likely to perceive that they provided excellent/very good/good care for their infant's teeth and/or gums. CONCLUSIONS: Parents who provide good infant oral health care are more likely to perceive they provide good care and more likely to have better personal dental health behaviors. This agrees with previous studies concerning older children. PMID- 26860442 TI - Production of germ cell-deficient salmonids by dead end gene knockdown, and their use as recipients for germ cell transplantation. AB - We previously established a spermatogonial transplantation model in fish using triploid recipients. Although triploid salmonids are sterile, they carry a limited number of immature triploid germ cells that potentially compete with the donor-derived germ cells for their niche. We therefore assessed the biological characteristics of germ cell-deficient gonads in rainbow trout for their suitability as recipients for germ cell transplantation in this study. Antisense morpholino oligonucleotides against the dead end gene were microinjected into the fertilized eggs of rainbow trout to eliminate endogenous germ cells, leaving only their supporting cells. Unlike similar approaches performed in zebrafish and medaka, these germ cell-deficient rainbow trout did not show a male-biased sex ratio. Approximately 30,000 spermatogonia were then transplanted into the body cavities of both germ cell-deficient and control recipients. The donor-derived germ cells showed significantly higher proliferation in the gonads of germ cell deficient recipients than those in the gonads of the control recipients. Finally, the applicability of the germ cell-deficient recipients for xenogeneic transplantation was evaluated by transplanting rainbow trout spermatogonia into germ cell-deficient masu salmon recipients. The resulting recipient salmon matured normally and produced trout gametes, and early survival of the resulting trout offspring was as high as that of the control offspring. Thus, dead end knockdown salmonids appear to be ideal recipients for the intraperitoneal transplantation of spermatogonia. PMID- 26860443 TI - Role of Carboxypeptidase N Invasion and Migration in Breast Cancer. AB - BACKGROUND: Carboxypeptidase N (CPN) is highly expressed in breast cancer and plays an important role in cleaving specific polypeptide fragments within the tumor microenvironment, so here we studied the important role of its invasion and migration in breast cancer. METHODS: MDA-MB-231, MDA-MB-468, and MCF-7 cells were selected for cell culture. We used real-time polymerase chain reaction (PCR) and western blotting to determine CPN gene and protein expression. If CPN was obviously expressed, we designed and synthesized a molecular sequence using an RNA interference approach to remove the CPN and observed its proliferation, migration, and invasion within tumor cells. RESULTS: Real-time PCR and western blotting show the following CPN expression: minimal in MDA-MB-468 cells but obvious in MDA-MB-231 and MCF7 cells. MDA-MB-231 breast cancer cell lines were selected for the control group and CPN was knocked out for the experimental group. Compared to the control group, the experimental group had significantly less migration and invasion. CONCLUSION: CPN may play an important biological function in breast cancer and will provide a new target for the effective diagnosis and treatment of breast cancer. PMID- 26860444 TI - Development and Validation of an Algorithm to Determine Spontaneous versus Provider-Initiated Preterm Birth in US Vital Records. AB - BACKGROUND: Determining whether initiation of preterm birth was spontaneous, or through labour induction or caesarean without labour or membrane rupture is critical in surveillance and aetiological research on preterm birth, although this information is not explicitly included on the US Birth Certificate. Algorithms combining several fields from birth certificates have been developed to infer the initiating event, but none has been validated against manual review of original obstetric records. Our objective was to develop a birth certificate based algorithm to determine initiation of preterm birth and validate it by manual review of original records. METHODS: We developed an algorithm from the 2003 US Standard Birth Certificate to determine spontaneous vs. indicated preterm birth. The algorithm was first tested on obstetrical records from 80 preterm (<37 weeks) births in Columbus OH (2006-12) abstracted by an obstetrics research nurse and reviewed by an obstetrician-gynecologist. Onset of delivery was spontaneous if the initiating event was premature rupture of membranes (PROM) or contractions, or indicated if the initiating event was induction or caesarean without labour or PROM. The algorithm was validated in an independent sample of 100 preterm births from four hospitals. RESULTS: Codes for tocolysis, fetal intolerance of labour, and anaesthesia during labour did not predict labour and were dropped. The final algorithm correctly classified 73/80 cases, kappa = 0.83. In the validation, 86/100 cases were correctly classified. The kappa statistic was 0.68 (0.52, 0.83); predictive values for spontaneous and indicated onset were 85% (75%, 92%) and 89% (71%, 98%). CONCLUSIONS: The algorithm distinguished spontaneous from indicated preterm birth, using birth certificates, with good accuracy. PMID- 26860446 TI - Societal Valorisation of New Knowledge to Improve Perinatal Health: Time to Act. PMID- 26860445 TI - Maternal C-Reactive Protein Concentration in Early Pregnancy and Child Autistic Traits in the General Population. AB - BACKGROUND: Exposure to elevated levels of inflammatory markers during pregnancy has been suggested as possible aetiologic factor in the occurrence of autism spectrum disorder (ASD). In this study, we investigated the prospective relation between maternal C-reactive protein (CRP) during early pregnancy and children's autistic traits in the general population. METHODS: In a large population-based cohort in the Netherlands, we measured maternal CRP levels before 18 weeks of gestation (N = 4165). Parents reported on their children's autistic traits at age 6 years using the Social Responsiveness Scale, and the Pervasive Developmental Problem scale. Regression models were used to examine the relation between maternal CRP levels and autistic traits in children. RESULTS: Compared with the reference group (CRP < 2.3 mg/L), elevated levels of CRP (>7.8 mg/L) in pregnant women were associated with higher Social Responsiveness Scale scores in children [beta = 0.055, 95% confidence interval (CI) 0.033, 0.078]; however, the effect was strongly attenuated after adjustment for several socioeconomic factors and in particular by maternal health-related factors including body mass index (fully adjusted model beta = 0.018, 95% CI -0.005, 0.042). We found no relation between maternal CRP levels and pervasive developmental problem. CONCLUSIONS: Our results suggest that the association between elevated levels of maternal CRP in pregnancy and autistic traits in children is confounded by maternal health-related and socioeconomic factors. Further studies are needed to explore whether other maternal inflammatory markers during pregnancy, as a response to maternal inflammation, are associated with the development of autistic traits in the offspring. PMID- 26860447 TI - RE: Analysis of Randomised Trials Including Multiple Births When Birth Size Is Informative. PMID- 26860448 TI - Response to Klebanoff. PMID- 26860449 TI - Superparamagnetic Luminescent MOF@Fe3O4/SiO2 Composite Particles for Signal Augmentation by Magnetic Harvesting as Potential Water Detectors. AB - Herein, we present the generation of a novel complex particle system consisting of superparamagnetic Fe3O4/SiO2 composite microparticle cores, coated with luminescent metal-organic frameworks (MOFs) of the constitution (infinity)(2)[Ln2Cl6(bipy)3].2bipy (bipy = 4,4'-bipyridine) that was achieved by intriguing reaction conditions including mechanochemistry. The novel composites combine the properties of both constituents: superparamagnetism and luminescence. The magnetic properties can be exploited to magnetically collect the particles from dispersions in fluids and, by gathering them at one spot, to augment the luminescence originating from the MOF modification on the particles. The luminescence can be influenced by chemical compounds, e.g., by quenching observed for low concentrations of water. Thus, the new composite systems present an innovative concept of property combination that can be potentially used for the detection of water traces in organic solvents as a magnetically augmentable, luminescent water detector. PMID- 26860450 TI - Anaphylaxis-triggered takotsubo syndrome: What is its prevalence? PMID- 26860451 TI - Emergent diagnosis and management of TASER penetrating ocular injury. PMID- 26860452 TI - Susceptibility of metallic magnesium implants to bacterial biofilm infections. AB - Magnesium alloys have promising mechanical and biological properties as biodegradable medical implant materials for temporary applications during bone healing or as vascular stents. Whereas conventional implants are prone to colonization by treatment resistant microbial biofilms in which bacteria are embedded in a protective matrix, magnesium alloys have been reported to act antibacterial in vitro. To permit a basic assessment of antibacterial properties of implant materials in vivo an economic but robust animal model was established. Subcutaneous magnesium implants were inoculated with bacteria in a mouse model. Contrary to the expectations, bacterial activity was enhanced and prolonged in the presence of magnesium implants. Systemic antibiotic treatments were remarkably ineffective, which is a typical property of bacterial biofilms. Biofilm formation was further supported by electron microscopic analyses that revealed highly dense bacterial populations and evidence for the presence of extracellular matrix material. Bacterial agglomerates could be detected not only on the implant surface but also at a limited distance in the peri-implant tissue. Therefore, precautions may be necessary to minimize risks of metallic magnesium containing implants in prospective clinical applications. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1489-1499, 2016. PMID- 26860453 TI - SEEDS - Strategic explorations of exoplanets and disks with the Subaru Telescope. AB - The first convincing detection of planets orbiting stars other than the Sun, or exoplanets, was made in 1995. In only 20 years, the number of the exoplanets including promising candidates has already accumulated to more than 5000. Most of the exoplanets discovered so far are detected by indirect methods because the direct imaging of exoplanets needs to overcome the extreme contrast between the bright central star and the faint planets. Using the large Subaru 8.2-m Telescope, a new high-contrast imager, HiCIAO, and second-generation adaptive optics (AO188), the most ambitious high-contrast direct imaging survey to date for giant planets and planet-forming disks has been conducted, the SEEDS project. In this review, we describe the aims and results of the SEEDS project for exoplanet/disk science. The completeness and uniformity of this systematic survey mean that the resulting data set will dominate this field of research for many years. PMID- 26860454 TI - Concentration of neddylation-related molecules in paranodal myelin of the peripheral nervous system. AB - Neddylation is a reversible post-translational modification in which a small ubiquitin-like molecule called NEDD8 covalently binds to substrate proteins. Although a recent study suggests that neddylation is essential for formation and maintenance of dendritic spines in the brain, the role of this protein modification in the peripheral nerves is wholly unknown. In this study, we demonstrate that neddylation-related molecules, NEDD8 and DCUN1D2 (defective in cullin neddylation 1, domain containing 2), were concentrated at the paranode of peripheral myelin, in addition to the myelinated and unmyelinated Schwann cell bodies. These proteins were localized mainly within larger fibers, but not in fibers with small diameters. Developmental analyses showed that these molecules first appeared at the paranode during later stages of myelination, and this characteristic distribution disappeared in sulfatide-deficient mice in which paranodal axo-glial junctions were disrupted. These results suggest that the myelin paranode may be one of the regions where neddylation occurs within the peripheral nerves. PMID- 26860455 TI - Postnatal development of the gastrin-releasing peptide system in the lumbosacral spinal cord controlling male reproductive function in rats. AB - A sexually dimorphic spinal gastrin-releasing peptide (GRP) system in the lumbosacral spinal cord, which projects to the lower spinal centers, controls erection and ejaculation in rats. However, little is known about the postnatal development of this system. In this study, we therefore examined the postnatal development of the male-dominant spinal GRP system and its sexual differentiation in rats using immunohistochemistry. Our results show that male-dominant expression of GRP is prominent from the onset of puberty and that sexually dimorphism persists into adulthood. These results suggest that androgen surge during male puberty plays an important role in the development and maintenance of the male-specific GRP function in the rat spinal cord. PMID- 26860456 TI - Errata to "Structure-function correlations of rat trigeminal primary neurons: Emphasis on club-like endings, a vibrissal mechanoreceptor". PMID- 26860457 TI - Helpfulness of rectoanal endosonography in diagnosis of sexual abuse in a child. AB - BACKGROUND: Clinical importance of sexual abuse in children has rapidly expanded in recent years, but despite of it, the lack of medical signs in the vast majority of sexual abuse cases, makes it difficult to assess. Given that, owing to our prior experience in endosonography (EUS) of the anal canal in child with anorectal malformations, we wanted to test EUS as a diagnostic method of sexual abuse in a child. PURPOSE: The purpose of our study is to present our experience in the use of anorectal EUS among children with suspected sexual abuse. MATERIALS/METHODS: We present 40 consecutive patients (34 boys and 6 girls, age: 10months-13years) recruited from April 2010 to December 2012, with suspected sexual abuse those made a transrectal EUS. RESULTS: The procedure was well tolerated in all patients without complications. Rectoanal EUS findings were normal in 27 patients and showed a partial interruption in the external anal sphincter in 8, scars in 2, double rail image in 2, and rectal wall hematoma in 1. CONCLUSIONS: The interpretation of findings in children depends of historical, physical, and laboratory findings. We believe that anal EUS is another aid in the constellation of clinical factors that could help in diagnostic of sexual abuse. PMID- 26860458 TI - Anomalously strong two-electron one-photon X-ray decay transitions in CO caused by avoided crossing. AB - The unique opportunity to study and control electron-nuclear quantum dynamics in coupled potentials offered by the resonant inelastic X-ray scattering (RIXS) technique is utilized to unravel an anomalously strong two-electron one-photon transition from core-excited to Rydberg final states in the CO molecule. High resolution RIXS measurements of CO in the energy region of 12-14 eV are presented and analyzed by means of quantum simulations using the wave packet propagation formalism and ab initio calculations of potential energy curves and transition dipole moments. The very good overall agreement between the experimental results and the theoretical predictions allows an in-depth interpretation of the salient spectral features in terms of Coulomb mixing of "dark" with "bright" final states leading to an effective two-electron one-photon transition. The present work illustrates that the improved spectral resolution of RIXS spectra achievable today may call for more advanced theories than what has been used in the past. PMID- 26860459 TI - Cortisol promotes endoplasmic glucose production via pyridine nucleotide redox. AB - Both increased adrenal and peripheral cortisol production, the latter governed by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), contribute to the maintenance of fasting blood glucose. In the endoplasmic reticulum (ER), the pyridine nucleotide redox state (NADP/NADPH) is dictated by the concentration of glucose-6-phosphate (G6P) and the coordinated activities of two enzymes, hexose-6 phosphate dehydrogenase (H6PDH) and 11beta-HSD1. However, luminal G6P may similarly serve as a substrate for hepatic glucose-6-phophatase (G6Pase). A tacit belief is that the G6P pool in the ER is equally accessible to both H6PDH and G6Pase. Based on our inhibition studies and kinetic analysis in isolated rat liver microsomes, these two aforesaid luminal enzymes do share the G6P pool in the ER, but not equally. Based on the kinetic modeling of G6P flux, the ER transporter for G6P (T1) preferentially delivers this substrate to G6Pase; hence, the luminal enzymes do not share G6P equally. Moreover, cortisol, acting through 11beta-HSD1, begets a more reduced pyridine redox ratio. By altering this luminal redox ratio, G6P flux through H6PDH is restrained, allowing more G6P for the competing enzyme G6Pase. And, at low G6P concentrations in the ER lumen, which occur during fasting, this acute cortisol-induced redox adjustment promotes glucose production. This reproducible cortisol-driven mechanism has been heretofore unrecognized. PMID- 26860460 TI - Gene signatures of postoperative atrial fibrillation in atrial tissue after coronary artery bypass grafting surgery in patients receiving beta-blockers. AB - Atrial tissue gene expression profiling may help to determine how differentially expressed genes in the human atrium before cardiopulmonary bypass (CPB) are related to subsequent biologic pathway activation patterns, and whether specific expression profiles are associated with an increased risk for postoperative atrial fibrillation (AF) or altered response to beta-blocker (BB) therapy after coronary artery bypass grafting (CABG) surgery. Right atrial appendage (RAA) samples were collected from 45 patients who were receiving perioperative BB treatment, and underwent CABG surgery. The isolated RNA samples were used for microarray gene expression analysis, to identify probes that were expressed differently in patients with and without postoperative AF. Gene expression analysis was performed to identify probes that were expressed differently in patients with and without postoperative AF. Gene set enrichment analysis (GSEA) was performed to determine how sets of genes might be systematically altered in patients with postoperative AF. Of the 45 patients studied, genomic DNA from 42 patients was used for target sequencing of 66 candidate genes potentially associated with AF, and 2,144 single-nucleotide polymorphisms (SNPs) were identified. We then performed expression quantitative trait loci (eQTL) analysis to determine the correlation between SNPs identified in the genotyped patients, and RAA expression. Probes that met a false discovery rate<0.25 were selected for eQTL analysis. Of the 17,678 gene expression probes analyzed, 2 probes met our prespecified significance threshold of false discovery rate<0.25. The most significant probe corresponded to vesicular overexpressed in cancer - prosurvival protein 1 gene (VOPP1; 1.83 fold change; P=3.47*10(-7)), and was up-regulated in patients with postoperative AF, whereas the second most significant probe, which corresponded to the LOC389286 gene (0.49 fold change; P=1.54*10(-5)), was down regulated in patients with postoperative AF. GSEA highlighted the role of VOPP1 in pathways with biologic relevance to myocardial homeostasis, and oxidative stress and redox modulation. Candidate gene eQTL showed a trans-acting association between variants of G protein-coupled receptor kinase 5 gene, previously linked to altered BB response, and high expression of VOPP1. In patients undergoing CABG surgery, RAA gene expression profiling, and pathway and eQTL analysis suggested that VOPP1 plays a novel etiological role in postoperative AF despite perioperative BB therapy. PMID- 26860461 TI - The value of uncertainty in critical illness? An ethnographic study of patterns and conflicts in care and decision-making trajectories. AB - BACKGROUND: With increasingly intensive treatments and population ageing, more people face complex treatment and care decisions. We explored patterns of the decision-making processes during critical care, and sources of conflict and resolution. METHODS: Ethnographic study in two Intensive Care Units (ICUs) in an inner city hospital comprising: non-participant observation of general care and decisions, followed by case studies where treatment limitation decisions, comfort care and/or end of life discussions were occurring. These involved: semi structured interviews with consenting families, where possible, patients; direct observations of care; and review of medical records. RESULTS: Initial non participant observation included daytime, evenings, nights and weekends. The cases were 16 patients with varied diagnoses, aged 19-87 years; 19 family members were interviewed, aged 30-73 years. Cases were observed for <1 to 156 days (median 22), depending on length of ICU admission. Decisions were made serially over the whole trajectory, usually several days or weeks. We identified four trajectories with distinct patterns: curative care from admission; oscillating curative and comfort care; shift to comfort care; comfort care from admission. Some families considered decision-making a negative concept and preferred uncertainty. Conflict occurred most commonly in the trajectories with oscillating curative and comfort care. Conflict also occurred inside clinical teams. Families were most often involved in decision-making regarding care outcomes and seemed to find it easier when patients switched definitively from curative to comfort care. We found eight categories of decision-making; three related to the care outcomes (aim, place, response to needs) and five to the care processes (resuscitation, decision support, medications/fluids, monitoring/interventions, other specialty involvement). CONCLUSIONS: Decision-making in critical illness involves a web of discussions regarding the potential outcomes and processes of care, across the whole disease trajectory. When measures oscillate between curative and comfort there is greatest conflict. This suggests a need to support early communication, especially around values and preferred care outcomes, from which other decisions follow, including DNAR. Offering further support, possibly with expert palliative care, communication, and discussion of 'trial of treatment' may be beneficial at this time, rather than waiting until the 'end of life'. PMID- 26860462 TI - The diagnostic accuracy of the MTBDRplus and MTBDRsl assays for drug-resistant TB detection when performed on sputum and culture isolates. AB - Although molecular tests for drug-resistant TB perform well on culture isolates, their accuracy using clinical samples, particularly from TB and HIV-endemic settings, requires clarification. The MTBDRplus and MTBDRsl line probe assays were evaluated in 181 sputum samples and 270 isolates from patients with culture confirmed drug-sensitive-TB, MDR-TB, or XDR-TB. Phenotypic culture-based testing was the reference standard. Using sputum, the sensitivities for resistance was 97.7%, 95.4%, 58.9%, 61.6% for rifampicin, isoniazid, ofloxacin, and amikacin, respectively, whereas the specificities were 91.8%, 89%, 100%, and 100%, respectively. MTBDRsl sensitivity differed in smear-positive vs. smear-negative samples (79.2% vs. 20%, p < 0.0001 for ofloxacin; 72.9% vs. 37%, p = 0.0023 for amikacin) but not by HIV status. If used sequentially, MTBDRplus and MTBDRsl could rule-in XDR-TB in 78.5% (22/28) and 10.5% (2/19) of smear-positive and smear-negative samples, respectively. On culture isolates, the sensitivity for resistance to rifampicin, isoniazid, ofloxacin, and amikacin was 95.1%, 96.1%, 72.3% and 76.6%, respectively, whereas the specificities exceeded 96%. Using a sequential testing approach, rapid sputum-based diagnosis of fluoroquinolone or aminoglycoside-resistant TB is feasible only in smear-positive samples, where rule-in value is good. Further investigation is required in samples that test susceptible in order to rule-out second-line drug resistance. PMID- 26860463 TI - Mortality predictors of Staphylococcus aureus bacteremia: a prospective multicenter study. AB - BACKGROUND: Staphylococcus aureus is one of the causes of both community and healthcare-associated bacteremia. The attributable mortality of S. aureus bacteremia (SAB) is still higher and predictors for mortality and clinical outcomes of this condition are need to be clarified. In this prospective observational study, we aimed to examine the predictive factors for mortality in patients with SAB in eight Turkish tertiary care hospitals. METHODS: Adult patients with signs and symptoms of bacteremia with positive blood cultures for S. aureus were included. All data for episodes of SAB including demographics, clinical and laboratory findings, antibiotics, and outcome were recorded for a 3 year (2010-2012) period. Cox proportional hazard model with forward selection was used to assess the independent effect of risk factors on mortality. A 28-day mortality was the dependent variable in the Cox regression analysis. RESULTS: A total of 255 episodes of SAB were enrolled. The median age of the patients was 59 years. Fifty-five percent of the episodes were considered as primary SAB and vascular catheter was the source of 42.1 %. Healthcare associated SAB was defined in 55.7 %. Blood cultures yielded methicillin-resistant S. aureus (MRSA) as a cause of SAB in 39.2 %. Initial empirical therapy was inappropriate in 28.2 %. Although overall mortality was observed in 52 (20.4 %), 28-day mortality rate was 15.3 %. Both the numbers of initial inappropriate empirical antibiotic treatment and the median hours to start an appropriate antibiotic between the cases of fatal outcome and survivors after fever onset were found to be similar (12/39 vs 60/216 and 6 vs 12 h, respectively; p > 0.05). High Charlson comorbidity index (CCI) score (p = 0.002), MRSA (p = 0.017), intensive care unit (ICU) admission (p < 0.001) and prior exposure to antibiotics (p = 0.002) all were significantly associated with mortality. The Cox analysis defined age [Hazard Ratio (HR) 1.03; p = 0.023], ICU admission (HR 6.9; p = 0.002), and high CCI score (HR 1.32; p = 0.002) as the independent predictive factors mortality. CONCLUSIONS: The results of this prospective study showed that age, ICU stay and high CCI score of a patient were the independent predictors of mortality and MRSA was also significantly associated with mortality in SAB. PMID- 26860465 TI - Tumor slice culture system to assess drug response of primary breast cancer. AB - BACKGROUND: The high incidence of breast cancer has sparked the development of novel targeted and personalized therapies. Personalization of cancer treatment requires reliable prediction of chemotherapy responses in individual patients. Effective selection can prevent unnecessary treatment that would mainly result in the unwanted side effects of the therapy. This selection can be facilitated by characterization of individual tumors using robust and specific functional assays, which requires development of powerful ex vivo culture systems and procedures to analyze the response to treatment. METHODS: We optimized culture methods for primary breast tumor samples that allowed propagation of tissue ex vivo. We combined several tissue culture strategies, including defined tissue slicing technology, growth medium optimization and use of a rotating platform to increase nutrient exchange. RESULTS: We could maintain tissue cultures for at least 7 days without losing tissue morphology, viability or cell proliferation. We also developed methods to determine the cytotoxic response of individual tumors to the chemotherapeutic treatment FAC (5-FU, Adriamycin [Doxorubicin] and Cyclophosphamide). Using this tool we designated tumors as sensitive or resistant and distinguished a clinically proven resistant tumor from other tumors. CONCLUSION: This method defines conditions that allow ex vivo testing of individual tumor responses to anti-cancer drugs and therefore might improve personalization of breast cancer treatment. PMID- 26860464 TI - Inflammasome components ASC and AIM2 modulate the acute phase of biomaterial implant-induced foreign body responses. AB - Detailing the inflammatory mechanisms of biomaterial-implant induced foreign body responses (FBR) has implications for revealing targetable pathways that may reduce leukocyte activation and fibrotic encapsulation of the implant. We have adapted a model of poly(methylmethacrylate) (PMMA) bead injection to perform an assessment of the mechanistic role of the ASC-dependent inflammasome in this process. We first demonstrate that ASC(-/-) mice subjected to PMMA bead injections had reduced cell infiltration and altered collagen deposition, suggesting a role for the inflammasome in the FBR. We next investigated the NLRP3 and AIM2 sensors because of their known contributions in recognising damaged and apoptotic cells. We found that NLRP3 was dispensable for the fibrotic encapsulation; however AIM2 expression influenced leukocyte infiltration and controlled collagen deposition, suggesting a previously unexplored link between AIM2 and biomaterial-induced FBR. PMID- 26860467 TI - Strategies for construction of the all-carbon macrocyclic skeleton of the ansamycin antibiotic-kendomycin. AB - Kendomycin, an ansamycin-type natural product first reported in 1996, possesses a series of attractive bioactivities and a unique all-carbon macrocyclic skeleton. To the date, seven total syntheses, two formal total syntheses and a number of synthetic studies on this hot molecule have been reported. In this short review article, we mainly survey and comment on these efforts regarding the difficult macrocyclization strategies. PMID- 26860466 TI - A marketing perspective to "delight" the "patient 2.0": new and challenging expectations for the healthcare provider. AB - BACKGROUND: The study aims at investigating the characteristics and the satisfaction determinants of the emerging patient profile. This profile appears to be more demanding and "empowered" compared to the ones traditionally conceived, asking for unconventional healthcare services and for a closer relationship with providers. METHODS: Both qualitative (semi-structured interviews and focus groups) and quantitative (survey) analyses were performed on a random sample of 2808 Italian citizens-patients. Analyses entailed descriptive statistics, bivariate analysis and linear regressions. RESULTS: Four relevant dimensions of patient 2.0 experience were identified through a literature review on experiential marketing in healthcare. Beta coefficients exhibited the effect that different healthcare experiential elements have on patient 2.0 satisfaction. CONCLUSIONS: Results allow to state that a new marketing approach, based on patient 2.0 characteristics and value drivers, should be adopted in the healthcare sector. Critical satisfaction drivers and new technological healthcare guidelines are identified in order to match the new patient profile needs. PMID- 26860468 TI - Practical synthesis of the C-ring precursor of paclitaxel from 3-methoxytoluene. AB - The practical synthesis of the C-ring precursor of paclitaxel starting from 3 methoxytoluene is described. Lipase-catalyzed kinetic resolution of a substituted cyclohexane-1,2-diol, derived from 3-methoxytoluene in three steps, successfully afforded a desired enantiomer with >99% ee, which was transformed to a cyclohexenone. 1,4-Addition of a vinyl metal species, followed by Mukaiyama aldol reaction with formalin in the presence of a Lewis acid provided the known C-ring precursor of paclitaxel in a 10 g scale. PMID- 26860469 TI - The enantioselective synthesis and biological evaluation of chimeric promysalin analogs facilitated by diverted total synthesis. PMID- 26860470 TI - Direct Band Gap Gallium Antimony Phosphide (GaSbxP(1-x)) Alloys. AB - Here, we report direct band gap transition for Gallium Phosphide (GaP) when alloyed with just 1-2 at% antimony (Sb) utilizing both density functional theory based computations and experiments. First principles density functional theory calculations of GaSbxP(1-x) alloys in a 216 atom supercell configuration indicate that an indirect to direct band gap transition occurs at x = 0.0092 or higher Sb incorporation into GaSbxP(1-x). Furthermore, these calculations indicate band edge straddling of the hydrogen evolution and oxygen evolution reactions for compositions ranging from x = 0.0092 Sb up to at least x = 0.065 Sb making it a candidate for use in a Schottky type photoelectrochemical water splitting device. GaSbxP(1-x) nanowires were synthesized by reactive transport utilizing a microwave plasma discharge with average compositions ranging from x = 0.06 to x = 0.12 Sb and direct band gaps between 2.21 eV and 1.33 eV. Photoelectrochemical experiments show that the material is photoactive with p-type conductivity. This study brings attention to a relatively uninvestigated, tunable band gap semiconductor system with tremendous potential in many fields. PMID- 26860471 TI - On the reliability of powder diffraction Line Profile Analysis of plastically deformed nanocrystalline systems. AB - An iron-molybdenum alloy powder was extensively deformed by high energy milling, so to refine the bcc iron domain size to nanometer scale (~10 nm) and introduce a strong inhomogeneous strain. Both features contribute to comparable degree to the diffraction peak profile broadening, so that size and strain contributions can be easily separated by exploiting their different dependence on the diffraction angle. To assess the reliability of Line Profile Analysis, results were compared with evidence from other techniques, including scanning and transmission electron microscopy and X-ray small angle scattering. Results confirm the extent of the size broadening effect, whereas molecular dynamics simulations provide insight into the origin of the local atomic, inhomogeneous strain, pointing out the role of dislocations, domain boundaries and interactions among crystalline domains. PMID- 26860472 TI - Validation of the Stroke and Aphasia Quality of Life Scale in a multicultural population. AB - PURPOSE: This study aimed to determine the reliability and validity of the Stroke and Aphasia Quality of Life Scale (SAQOL-39 g) and its Mandarin adaptation SAQOL CSg in Singaporean stroke patients. METHOD: First-time stroke survivors were recruited at three months post-stroke and underwent a series of questionnaires in their dominant language (English/Mandarin). This included: SAQOL-39 g/CSg, National University Hospital System (NUHS) Aphasia Screening Test, Barthel Index, Modified Rankin Scale, Mini Mental State Examination, Frontal Assessment Battery, Center for Epidemiologic Studies Depression Scale and the Eurol-Qol Health Questionnaire (EQ-5D). The SAQOL-39 g/SAQOL-CSg was repeated within 1 week (+/- 6 days). RESULTS: Ninety-four participants (96.9%) were able to self-report and their results presented here. Both the SAQOL-39 g/SAQOL-CSg showed good internal consistency (alpha = 0.96/0.97), test-retest reliability (ICC= 0.99/0.98), convergent (rs =0.64-0.81 and 0.66-0.88, respectively) and discriminant (rs = 0.35-0.53 and 0.48-0.62, respectively) validity. The correlation between the SAQOL-39 g and the EQ-5D Visual Analogue Scale was 0.27. Further inspection of the EQ-5DVAS scores revealed correlations in different directions for Malay versus Chinese participants. CONCLUSIONS: Both the SAQOL-39 g and SAQOL-CSg demonstrated good reliability and validity. Our results suggested some influence of ethnicity in self-rating of health status in relation to SAQOL-39 g scores. Further research is warranted to examine its use with stroke survivors with greater stroke severity and over time. Implications for Rehabilitation Validation of SAQOL in Singapore: Both the SAQOL-39g and the SAQOL-CSg may be used to measure the HRQoL of stroke survivors with and without aphasia in Singapore. Further investigation is required to examine use with stroke survivors with greater stroke severity and over time. PMID- 26860473 TI - Establishing a relationship between topical nasal steroids and raised intra ocular pressure. PMID- 26860474 TI - Rhodopsins carrying modified chromophores--the 'making of', structural modelling and their light-induced reactivity. AB - A series of vitamin-A aldehydes (retinals) with modified alkyl group substituents (9-demethyl-, 9-ethyl-, 9-isopropyl-, 10-methyl, 10-methyl-13-demethyl-, and 13 demethyl retinal) was synthesized and their 11-cis isomers were used as chromophores to reconstitute the visual pigment rhodopsin. Structural changes were selectively introduced around the photoisomerizing C11=C12 bond. The effect of these structural changes on rhodopsin formation and bleaching was determined. Global fit of assembly kinetics yielded lifetimes and spectral features of the assembly intermediates. Rhodopsin formation proceeds stepwise with prolonged lifetimes especially for 9-demethyl retinal (longest lifetime tau3 = 7500 s, cf., 3500 s for retinal), and for 10-methyl retinal (tau3 = 7850 s). These slowed-down processes are interpreted as either a loss of fixation (9dm) or an increased steric hindrance (10me) during the conformational adjustment within the protein. Combined quantum mechanics and molecular mechanics (QM/MM) simulations provided structural insight into the retinal analogues-assembled, full-length rhodopsins. Extinction coefficients, quantum yields and kinetics of the bleaching process (MUs-to-ms time range) were determined. Global fit analysis yielded lifetimes and spectral features of bleaching intermediates, revealing remarkably altered kinetics: whereas the slowest process of wild-type rhodopsin and of bleached and 11-cis retinal assembled rhodopsin takes place with lifetimes of 7 and 3.8 s, respectively, this process for 10-methyl-13-demethyl retinal was nearly 10 h (34670 s), coming to completion only after ca. 50 h. The structural changes in retinal derivatives clearly identify the precise interactions between chromophore and protein during the light-induced changes that yield the outstanding efficiency of rhodopsin. PMID- 26860475 TI - Stimulatory effect of the secretogranin-ll derived peptide secretoneurin on food intake and locomotion in female goldfish (Carassius auratus). AB - Secretoneurin (SN) is a conserved peptide derived by proteolytic processing from the middle domain of the ~600 amino acid precursor secretogranin-II (SgII). Secretoneurin is widely distributed in secretory granules of endocrine cells and neurons and has important roles in reproduction as it stimulates luteinizing hormone release from the pituitary. A potential new role of SN in goldfish feeding is the subject of this study. Firstly, we established that acute (26 h; p<0.0001) and short-term (72 h; p=0.016) fasting increased SgIIa precursor mRNA levels 1.25-fold in the telencephalon, implicating SN in the control of feeding. Secondly, we determined that intracerebroventricular injections of the type A SN (SNa; 0.2 and 1 ng/g BW) increased food intake and locomotor behavior by 60 min. Fish injected with the lower and higher doses of SNa (0.2 and 1 ng/g) respectively exhibited significant 1.77- and 2.58-fold higher food intake (p<0.0001) than the saline-injected control fish. Locomotor behavior was increased by 1.35- and 2.26-fold for 0.2 ng/g SNa (p=0.0001) and 1 ng/g SNa (p<0.0001), respectively. Injection of 1 ng/g SNa increased mRNA levels of hypothalamic neuropeptide Y 1.36-fold (p=0.038) and decreased hypothalamic cocaine-and amphetamine-regulated transcript by 33% (p=0.01) at 2h and 5h post injection, respectively. These data suggest interactions of SNa with stimulatory and inhibitory pathways of food intake control in fish. PMID- 26860477 TI - Is Migration Affecting Prevalence, Awareness, Treatment and Control of Hypertension of Men in Kerala, India? AB - We assessed hypertension prevalence, awareness, treatment and control among male gulf migrant and non-migrant workers in Kerala state of India. We did a cross sectional survey of 191 migrant and 193 non-migrant men aged 25-64 years selected using a multistage random sampling method. Using World Health Organization STEPS approach, we collected information on demographics, STEP 1 variables and measured STEP-2 variables. Multivariate analysis was used to find the relation between migration and hypertension. Age adjusted hypertension prevalence was 57.6 % among migrants and 31.7 % among non-migrants (p < 0.05). Migrants were more likely to be hypertensive (OR 3.00, 95 % CI 1.83-4.94) than non-migrants after adjusting for age, STEP 1 and STEP 2 variables. Though not statistically significant (p = 0.109), awareness of hypertension was lower among migrants (43.5 %) compared to non migrants (56.9 %). Treatment (migrants: 34 %, non-migrants: 53 %, p < 0.05) and control (migrants: 12 %, non-migrants: 48 %, p < 0.001) of hypertension were lower among migrants. Greater attention to improve the treatment and control of hypertension among migrants is warranted in this population. PMID- 26860478 TI - Different Context but Similar Cognitive Structures: Older Adults in Rural Bangladesh. AB - Most research in cognitive aging is based on literate participants from high income and Western populations. The extent to which findings generalize to low income and illiterate populations is unknown. The main aim was to examine the structure of between-person differences in cognitive functions among elderly from rural Bangladesh. We used data from the Poverty and Health in Aging (PHA) project in Bangladesh. The participants (n = 452) were in the age range 60-92 years. Structural equation modeling was used to estimate the fit of a five-factor model (episodic recall, episodic recognition, verbal fluency, semantic knowledge, processing speed) and to examine whether the model generalized across age, sex, and literacy. This study demonstrates that an established model of cognition is valid also among older persons from rural Bangladesh. The model demonstrated strong (or scalar) invariance for age, and partial strong invariance for sex and literacy. Semantic knowledge and processing speed showed weak (or metric) sex invariance, and semantic knowledge demonstrated also sensitivity to illiteracy. In general, women performed poorer on all abilities. The structure of individual cognitive differences established in Western populations also fits a population in rural Bangladesh well. This is an important prerequisite for comparisons of cognitive functioning (e.g., declarative memory) across cultures. It is also worth noting that absolute sex differences in cognitive performance among rural elderly in Bangladesh differ from those usually found in Western samples. PMID- 26860479 TI - Nurse staffing to patient ratios and mortality in neonatal intensive care. PMID- 26860481 TI - Four-Dimensional Power Doppler Sonography With the HDlive Silhouette Mode in Antenatal Diagnosis of a Right Aortic Arch With an Aberrant Left Subclavian Artery. PMID- 26860480 TI - The effects of a one-to-one nurse-to-patient ratio on the mortality rate in neonatal intensive care: a retrospective, longitudinal, population-based study. AB - OBJECTIVE: To estimate the effect of the provision of a one-to-one nurse-to patient ratio on mortality rates in neonatal intensive care units. DESIGN: A population-based analysis of operational clinical data using an instrumental variable method. SETTING: National Health Service neonatal units in England contributing data to the National Neonatal Research Database at the Neonatal Data Analysis Unit and participating in the Neonatal Economic, Staffing, and Clinical Outcomes Project. PARTICIPANTS: 43 tertiary-level neonatal units observed monthly over the period January 2008 to December 2012. INTERVENTION: Proportion of neonatal intensive care days or proportion of intensive care admissions for which one-to-one nursing was provided. OUTCOMES: Monthly in-hospital intensive care mortality rate. RESULTS: Over the study period, the provision of one-to-one nursing in tertiary neonatal units declined from a median of 9.1% of intensive care days in 2008 to 5.9% in 2012. A 10 percentage point decrease in the proportion of intensive care days on which one-to-one nursing was provided was associated with an increase in the in-hospital mortality rate of 0.6 (95% CI 1.2 to 0.0) deaths per 100 infants receiving neonatal intensive care per month compared with a median monthly mortality rate of 4.5 deaths per 100 infants per month. The results remained robust to sensitivity analyses that varied the estimation sample of units, the choice of instrumental variables, unit classification and the selection of control variables. CONCLUSIONS: Our study suggests that decreases in the provision of one-to-one nursing in tertiary-level neonatal intensive care units increase the in-hospital mortality rate. PMID- 26860482 TI - Prognostic Value of Fetal Thymus Size in Intrauterine Growth Restriction. AB - OBJECTIVES: Our aim was to evaluate the size of the fetal thymus by sonography in pregnancies with intrauterine growth restriction (IUGR) and to search for a possible relationship between a small fetal thymus and adverse perinatal outcomes. METHODS: The transverse diameter of the fetal thymus was prospectively measured in 150 healthy and 143 IUGR fetuses between 24 and 40 weeks' gestation. The fetuses with IUGR were further divided according to normal or abnormal Doppler assessment of the umbilical and middle cerebral arteries and ductus venosus. Measurements were compared with reference ranges from controls. To determine which perinatal outcomes were independently associated with a small fetal thymus, a multivariate logistic regression analysis was performed. RESULTS: Thymus size was significantly lower in IUGR fetuses compared to controls (P < .05). Among IUGR fetuses, thymus size was significantly smaller in IUGR fetuses with abnormal Doppler flow compared to normal flow (P < .05). A small thymus in IUGR fetuses was independently associated with early delivery (odds ratio [OR], 1.24; 95% confidence interval [CI], 1.05-1.49; P= .023), respiratory distress syndrome (OR, 1.36; 95% CI, 1.09-1.78; P= .005), early neonatal sepsis (OR, 1.65; 95% CI, 1.11-2.42; P= .001), and a longer stay in the neonatal intensive care unit (OR, 1.33; 95% CI, 1.08-1.71; P = .017). CONCLUSIONS: Intrauterine growth restriction is associated with fetal thymic involution, and a small fetal thymus is an early indicator of adverse perinatal outcomes in pregnancies complicated by IUGR. PMID- 26860483 TI - Atypical Presentations of Molar Pregnancy: Diagnostic Roles of Imaging, beta Human Chorionic Gonadotropin Measurement, and p57 Immunostaining. AB - In modern practice , the diagnosis of molar pregnancy is made at an early gestational age. The opportunity to diagnose gestational trophoblastic disease (GTD) using sonography alone occurs less frequently. The classic appearance of a "snowstorm" in the endometrial cavity and bilateral theca lutein cysts still applies to the diagnosis of second-trimester GTD. The diagnosis of first trimester GTD requires increased clinical suspicion. If the sonographic appearance of the pregnancy is atypical, GTD should be included in the differential diagnosis. Additional nonimaging criteria such as serial quantitative beta-human chorionic gonadotropin levels, pathologic examination, and p57 (cyclin-dependent kinase inhibitor 1C protein) immunostaining can accurately confirm the diagnosis of GTD. PMID- 26860484 TI - Spatiotemporal Image Correlation and Volumetric Impedance Indices in the Neonatal Brain: Proof of Concept and Preliminary Reproducibility. AB - OBJECTIVES: Changes in tissue perfusion can be critically important in the vulnerable neonate, but they are very difficult to assess at the bedside. Spatiotemporal image correlation (STIC) sonography is an exciting concept that allows assessment of blood flow by rearranging and merging multiple 2-dimensional color images to create serial 3-dimensional images showing regional blood flow throughout the cardiac cycle. Variations in tissue blood flow may reflect tissue impedance and perfusion. The aim of this study was to demonstrate that it is possible to use STIC images to evaluate tissue impedance in the neonatal brain. METHODS: Spatiotemporal image correlation data sets were acquired by cranial sonography in 19 neonates. Offline data analysis was performed by using virtual organ computer-aided analysis. With the use of STIC images from different phases of the cardiac cycle, impedance indices were calculated, based on maximum (systolic), minimum (diastolic), and mean virtual organ computer-aided analysis values, in the same way that resistive indices are calculated in 2-dimensional sonography. RESULTS: Volumetric indices for tissue impedance were obtained for all neonates. Intraclass correlation coefficients (95% confidence intervals) for volumetric impedance indices were as follows: systolic/diastolic ratio, 0.793 (0.615-0.906); pulsatility index, 0.790 (0.609-0.905); and resistive index, 0.783 (0.598-0.901). Interclass correlation coefficients for image processing and analysis were as follows: systolic/diastolic ratio, 0.868 (0.692-0.947); pulsatility index, 0.904 (0.772-0.962); and resistive index, 0.914 (0.794-0.966). CONCLUSIONS: This study shows that STIC data sets can be used to calculate volumetric impedance indices in the neonatal brain. Preliminary assessment shows that this technique appears reliable and allows evaluation of regional tissue impedance in the neonate. PMID- 26860485 TI - 5-HT3 Receptor Antagonists for Propofol Injection Pain: A Meta-Analysis of Randomized Controlled Trials. AB - BACKGROUND AND OBJECTIVES: 5-hydroxytryptamine3 (5-HT3) receptor antagonists have been commonly used to reduce propofol injection pain. The aim of this meta analysis was to evaluate the efficacy and safety of 5-HT3 receptor antagonists in decreasing the incidence and intensity of propofol injection pain. METHODS: Online databases of Pubmed, Embase and the Cochrane Central Register of Controlled Trials were searched as well as reference lists of included studies and recent reviews. Eligible randomized controlled trials (RCTs) assessing the efficacy and safety of 5-HT3 receptor antagonists for propofol injection pain were identified. The outcomes included the incidence and intensity of propofol injection pain and adverse effects. We calculated risk ratios (RR) with 95 % confidence intervals (CIs) for dichotomous data and adopted fixed or random effects model when proper. RESULTS: A total of eight RCTs were included in the final analysis. Compared with the control group, 5-HT3 receptor antagonists were related to a decreasing incidence of propofol injection pain (RR 0.43, 95 % CI 0.33-0.56, P < 0.05). Besides, they also effectively alleviated the severity of propofol injection pain. They significantly reduced the number of patients with moderate (RR 0.21, 95 % CI 0.15-0.30, P < 0.05) and severe pain (RR 0.16, 95 % CI 0.10-0.25, P < 0.05) during propofol injection. 5-HT3 receptor antagonists and lidocaine were equally effective in preventing propofol injection pain. Moreover, only one article mentioned the adverse effects of 5-HT3 receptor antagonists in two patients. CONCLUSION: Our meta-analysis indicates that 5-HT3 receptor antagonists can effectively reduce the incidence and severity of propofol injection pain. Additionally, 5-HT3 receptor antagonists may become the alternatives to lidocaine in attenuating propofol injection pain. However, evidence is still limited for the safety of 5-HT3 receptor antagonists on propofol injection pain. PMID- 26860486 TI - Mapping of the OAB-SF Questionnaire onto EQ-5D in Spanish Patients with Overactive Bladder. AB - BACKGROUND AND OBJECTIVE: Mapping disease-specific measures onto generic preference-based indexes allows estimating utility values in specific conditions to determine gain of quality-adjusted-life-years when the status of condition varies. The aim of this study was to map a disease specific scale, the Overactive Bladder Questionnaire 5-dimensional health classification system (OAB-5D) derived from the Overactive Bladder questionnaire-Short Form (OABq-SF), onto a preference based scale, the EuroQol-5D (EQ-5D), in a sample of patients with overactive bladder (OAB) in a Spanish population. METHOD: A survey addressed to value the health states was conducted among 246 patients at 18 clinics of urology from Spain. A total of 43 out of 243 possible health states have been valued, using VAS (Visual Analog Scale) and TTO (time trade-off) techniques. In addition, ordinary least squares (OLS), generalized linear models (GLM) and Tobit models were estimated. Resulting models were compared and the best one was selected in terms of goodness of fit measures, attribute sign, coefficient magnitude, and statistical significance of regression coefficients. Finally, the internal validity of the best model was calculated by bootstrap resampling. RESULTS: The best model to map the OAB-5D onto EQ-5D could be estimated and the stability of parameter estimations was proved. The mentioned model estimated through OLS regression attained R (2) value of 0.892, with the aggregated data; with GLM (efficient maximum likelihood regression), Pearson chi (2) of 15.3 has been obtained; AIC (Akaike information criterion) = -550.9 and BIC (Bayesian information criterion) = -475.4. OLS model included the following OABq-SF items (and range of weights): A1 (0.102, 0.216); A3 (0.070, 0.171); B3 (0.071, 0.078); B1 (0.076, 0.136); B2 (-0.132, -0.028). CONCLUSION: It is possible to map the OAB 5D scores onto EQ-5D in the Spanish population, allowing estimating EQ-5D utility scores from OAB specific health conditions. PMID- 26860487 TI - Due time driven surgery scheduling. AB - In many hospitals there are patients who receive surgery later than what is medically indicated. In one of Europe's largest hospitals, the University Hospital Leuven, this is the case for approximately every third patient. Serving patients late cannot always be avoided as a highly utilized OR department will sometimes suffer capacity shortage, occasionally leading to unavoidable delays in patient care. Nevertheless, serving patients late is a problem as it exposes them to an increased health risk and hence should be avoided whenever possible. In order to improve the current situation, the delay in patient scheduling had to be quantified and the responsible mechanism, the scheduling process, had to be better understood. Drawing from this understanding, we implemented and tested realistic patient scheduling methods in a discrete event simulation model. We found that it is important to model non-elective arrivals and to include elective rescheduling decisions made on surgery day itself. Rescheduling ensures that OR related performance measures, such as overtime, will only loosely depend on the chosen patient scheduling method. We also found that capacity considerations should guide actions performed before the surgery day such as patient scheduling and patient replanning. This is the case as those scheduling strategies that ensure that OR capacity is efficiently used will also result in a high number of patients served within their medically indicated time limit. An efficient use of OR capacity can be achieved, for instance, by serving patients first come, first served. As applying first come, first served might not always be possible in a real setting, we found it is important to allow for patient replanning. PMID- 26860488 TI - Protective effect of cyclodextrins on the quality parameters of roast preserved pepper. AB - Total phenolics (TP), vitamin C, antioxidant activity and colour of preserved peppers were evaluated at 4, 25 and 50 C storage during 30-day intervals. Except for 4 C, TP decreased during storage at 25 C and 50 C, being softer for fortified samples with beta-CDs. The protective effect was evident, since 50 C samples containing beta-CDs exhibited lower TP loss (19%) than control samples (38%) for 5 months storage. A decrease in the vitamin C content was observed for both samples as time and temperature progressed. In samples stored at 50 C the protective effect of beta-CD only was evident at the first month, since fortified samples showed lower vitamin C loss (10%) than control samples. The fortified samples with beta-CDs exhibited lowest antioxidant activity loss (40%) during 90 day storage at 50 C, than control samples (64%). The colour changes were in line with those observed for total phenolics and at the end of study, the presence of 1% beta-CDs delayed the darkening of samples at both (25 and 50 C) storage conditions. PMID- 26860489 TI - Effect of vegetable proteins on physical characteristics of spray-dried tomato powders. AB - In the present study, the effectiveness of different vegetable proteins (pea protein isolate, soy protein isolate and zein from maize) at two different ratios (1% and 5%) on product yield and physical properties of spray-dried pulpy tomato juice was investigated. Additionally, these proteins were compared with whey protein concentrate which has a superior effect on spray dried products at the same concentrations. Additionally, plain tomato juice was also spray dried for comparison with vegetable proteins. The product yield of the tomato powders dried with the vegetable proteins was lower than with the whey protein concentrate. Among vegetable proteins, the highest product yield was produced with 1% soy protein isolate. In all products, there was a slight colour difference between the reconstituted tomato powders and the raw tomato juice, which indicated that pulpy tomato juice can be spray dried with minor colour change. All powders had unique free-flowing properties estimated as Carr index and Hausner ratio due to their large particles. PMID- 26860490 TI - Effects of combined epidural analgesia with total intravenous anesthesia on risky patients underwent major abdominal surgery. AB - OBJECTIVES: The aim of this study is to investigate the effects of combined epidural analgesia with total intravenous anaesthesia and only total intravenous anaesthesia on the different clinical parameters. METHODS: Sixty high risk patients undergoing a major abdominal surgical procedure were included in this prospective, double blind, randomized study. Induction of anaesthesia was performed with IV remifentanil 0.5ug/kg and propofol titrated to achieve bispectral index score between 40 and 50. after intubation; in Group E, 0.1% bupivacaine and 2 ug/mL fentanyl were administered by an infusion rate at 0.15 ml/kg/h via the epidural catheter and Group C received epidural normal saline as same infusion rate. RESULTS: In group E, intraoperative MAP values were significantly lower than those in group C (p<0.05). Time of extubation, time of eye opening with audible warning and time of verbal response was significantly lower in group E than those in group C. Total anaesthetic drug consumption was significantly higher in group C than those in group E (p<0.05). CONCLUSION: Based on lower requirements for propofol and remifentanil as well as the favourable effects on clinical parameters; we conclude that bispectral index score guided combined epidural with total intravenous anaesthesia is superior to solely total intravenous anaesthesia in this type of surgery. PMID- 26860491 TI - The effects of fatigue and pain on daily life activities in systemic lupus erythematosus. AB - OBJECTIVES: The aim of this study was to determine the effects of pain and fatigue on daily life activities of systemic lupus erythematosus (SLE) patients. METHODS: The study sample included 74 SLE patients who presented to outpatient departments of a university hospital and two local hospitals between 30.9.2009 and 15.5.2010. Data was collected using the Fatigue Severity Scale, Katz's Activity's Daily Living Index, Lawton and Brody's Instrumental Activities of Daily Living, and the McGill Pain Questionnaire. RESULTS: The mean scores were 6.0 (fatigue) on the Fatigue Severity Scale, 18.0 (independent) on the Daily Life Activities Index, 24.0 (independent) on the Instrumental Daily Life Activities Index, and 1.56 (discomforting) on the McGill Pain Scale for pain felt at the moment of questioning. A low-level negative relationship was observed between the scores on the Fatigue Severity Scale and the Daily Life Activities Index (p<0.05, r=-0.298), and between Fatigue and Instrumental Daily Life Activities scores (p<0.05, r=-0.354). A medium-level positive relationship was observed between the scores on the Fatigue Severity Scale and the McGill Pain Scale (p<0.05, r=0.478). CONCLUSION: This study determined that pain and fatigue affected the daily lives of SLE patients. The study should be repeated on a larger sample. PMID- 26860492 TI - Efficacy of conventional ultrasound therapy on myofascial pain syndrome: a placebo controlled study. AB - OBJECTIVES: Myofascial pain syndrome (MPS) is a complex pain syndrome characterized with trigger points (TP) in skeletal muscles. We aimed to assess the efficacy of ultrasound (US) therapy, which is one of the main devices used in physical medicine and rehabilitation, for the treatment of TP in MPS. METHODS: Fifty nine patients (49 females, 10 males) with active TP on the upper trapezius fibers were randomized into the treatment (n=30) and the control groups (n=29). The treatment group received conventional US therapy for 6 minutes, on 1.5 Watt/cm2 dose with 1 MHz frequency for 15 days whereas a placebo US therapy was administered to the control group. Prior to the treatment, immediately and 3 months later pain severity during rest and physical activity was assessed with visual analog scale (VAS), TP tenderness was measured with 0-5 scale, pressure pain threshold (PPT) was analyzed with algometer and the depression level was evaluated with Beck's depression questionnaire (BDP) by a clinician blinded to the groups. RESULTS: The mean age of the patients were 37.43+/-9.07 and 35.83+/ 5.68 years, in the treatment and control groups, respectively. Compared to the pre-treatment values VAS, 0-5 scale and BDP scores decreased (p<0.01) along with an increase in PPT (p<0.01) in both groups at the follow-up visits. 0-5 scales and BDP scores were significantly lower and PPT was significantly higher in the treatment group, compared to the control group (p<0.001). CONCLUSION: Our results revealed that US treatment is effective on MPS. PMID- 26860493 TI - [Pain evaluation in patients with chronical renal failure undergoing hemodialysis]. AB - OBJECTIVES: Hemodialysis is a vital therapy in treatment of chronical renal failure. Pain is a complaint seen at every stage of chronical renal failure and is a part of clinical status. We aimed to investigate pain and its causes and the sufficiency of pain treatment in use. METHODS: Patients aged 18-60 undergoing hemodialysis were included in this study. Pain evolution was obtained by form of Algology. Neuropathic pain symptoms and signs were evaluated by using LANNS. RESULTS: 53 patients undergoing hemodialysis (75.7%) complained of pain. The types of pain were recorded to be headache (31 patients, 58.5%), lower extremity pain (21 patients, 39.6%) and pain due to cramps (28 patients, 52.8%). We saw that 81.4% of our patients were capable of doing on their own and that the pain did not affect daily activities of our patients. There were 37 patients (71.8%) who had LANSS score >=12. Patients included in this study answered the question "Did you get any treatment for this pain?" as NO in 58.5% (31 patients) and as YES in 41% (21 patients). Nevertheless, 29 patients (54.7%) stated that they used drugs because of the pain and 24 patients (45.3%) stated that they haven't used any drugs for pain management. CONCLUSION: The patients with chronical diseases like chronical renal failure, we believe that pain should be interrogated and assessed and along with the treatment of chronical renal failure, patients should be treated for pain and a pain-free life must be provided to these group of patients. PMID- 26860494 TI - [The donor site pain assessment of the patients who were reconstructed split thickness graft]. AB - OBJECTIVES: In this study we examined the donor site pain intensity of the patients who were reconstructed by split thickness skin graft (STSG) due to tissue defect. METHODS: This descriptive study was performed in a Plastic and Reconstructive Surgery Clinic of a State Hospital in Istanbul. Sampling selection wasn't made, all (31) cases were studied with STSG in 2013. As data collection forms, we used Patient Information Form and Visual Analog Scale (VAS). In the analysis of the data percentage, Kruskal-Wallis and Mann-Whitney-U tests were used. RESULTS: 38.71% of the patients were female and 61.29% were male. It was determined that grafting application was mostly made in the lower extremity and 61% of the patients were able to perform individual functions independently. It was observed that pain intensity increased as the donor area expanded. It was also determined that semi-dependent patients' pain intensity was higher than independent patients'. In 64.52% of the patients graft donor area was wider than 10cm2. The postoperative pain intensity of the patients who were reconstructed by STSG in the lower extremity was higher than patients who were reconstructed by STSG in the upper extremity area. CONCLUSION: It was observed that the donor area pain intensity of patients was the most severe on the first day after surgery and the least severe on the sixth day after surgery. In conclusion, the pain evaluation of the donor area has to be assessed by the nurse on the first day after surgery. PMID- 26860495 TI - Analgesic efficacy of transversus abdominis plane block in neonates and early infants for colostomy and reversal of colostomy. AB - The application of ultrasound-guided transversus abdominis plane (TAP) block in paediatric population is gaining popularity among anaesthetists. We present a case series of ultrasound-guided TAP block in ten neonate and infants undergoing colostomy and reversal of stoma. Classical TAP as described by Hebbard was carried out and a maximum dosage of 1ml/kg of 0.25% levobupivacaine was injected. Pain score was assessed using Neonatal Infant Pain Scale for 24 hours. In all patients, the block was successful with minimal hemodynamic changes intraoperatively and no additional systemic analgesia was needed intraoperative and immediate postoperatively. Ultrasound-guided TAP block has an important role in providing safe and effective analgesia for colostomy creation and reversal of stoma surgeries in paediatric population. PMID- 26860496 TI - The application of epidural anesthesia in pregnant woman with uncorrected tetralogy of Fallot: a case report. AB - Tetralogy of Fallot is the most common cyanotic congenital cardiac disease. The hemodynamic changes which are present immediately after abdominal delivery may be resulted with serious, life-threatening multiorgan complications. Therefore the choice of anesthesia is very difficult. We describe the case of pregnant, 33 weeks gestation, with uncorrected tetralogy of Fallot who underwent caesarian section. The epidural anesthesia was performed uneventfully. After having stabile vital signs and a good general condition patient was followed up at the intensive care unit for 4 days. She was transferred to the obstetric service. We think that application of epidural anaesthesia with fragmented and increasing doses of slow levobupivacain in pregnant women with tetralogy of Fallot is safe. Nonetheless, this data of ours will grow stronger with the increase of the clinical application amount. PMID- 26860497 TI - Painful ophthalmoplegia: a case report and literature review. AB - Painful ophthalmoplegia consists of periorbital or hemicranial pain with ipsilateral ocular motor nerve palsies. There are many etiologies of painful ophthalmoplegia. Tolosa-Hunt syndrome (THS) is an uncommon disease caused by non specific inflammation of the cavernous sinus, superior orbital fissure and the apex of the orbit. A 45-year-old female reported episodes of reversible left eye pain and diplopia. Examination showed periorbital oedema and left palpebral semiptosis, paresis of the partial left third nerve palsy with normal pupillary reactions, fourth and sixth left cranial nerves, and hypoesthesia over the first and second division of the left trigeminal nerve. Blood analysis, postcontrast cranial and orbital magnetic resonance (MR) imaging, cranial MR angiography and CSF analysis demonstrated no abnormalities. The clinical diagnosis satisfies the criteria for THS. After steroid therapy her symptoms and clinical signs dramatically reverses. Painful ophthalmoplegia with inflammatory conditions such as THS is highly responsive to corticosteroids but should be diagnoses of exclusion. The THS diagnosis should be used rarely and with great caution. PMID- 26860498 TI - [An overlooked clinical entity: notalgia paresthetica]. PMID- 26860499 TI - Has Choosing Wisely(r) affected rates of dual-energy X-ray absorptiometry use? AB - Reducing overuse of tests such as dual-energy X-ray absorptiometry (DXA) scans in younger women is an important quality issue. We evaluated trends in DXA ordering before and after Choosing Wisely recommendations were released. We found no significant difference in ordering trends suggesting that other initiatives are needed to change behavior. INTRODUCTION: Reducing overuse of tests such as dual energy X-ray absorptiometry (DXA) scans in younger women is an important quality issue, but trends in care are difficult to change. We evaluated (1) trends in DXA ordering before and after the Choosing Wisely recommendation release and (2) patterns of key characteristics that indicate a potentially appropriate DXA scan order. METHODS: We performed a retrospective longitudinal analysis of electronic health record data at a multi-specialty, ambulatory care network of 34 practices across Maryland and Washington, DC. Since the Choosing Wisely DXA recommendation was released April 2012, the study periods were April-December 2011 (pre initiative) and April-December 2012 (post-initiative). Women between 50 and 64 years with primary care encounters, and primary care providers who saw ten or more women in the study population in both pre and post periods were included. RESULTS: For 42,320 eligible patients, the mean provider ordering rate was 2.6 % pre-initiative and 2.0 % post-initiative; there was no significant difference in trend over time. Over 70 % of the population had no characteristics associated with potentially appropriate DXA ordering. Low body mass index, current smoker status, and osteopenia were the most common characteristics indicating potentially appropriate DXA orders. Patients with any of these three characteristics had DXA ordering rates between 3-20 %. CONCLUSIONS: The trend in provider ordering rates of DXA scans did not decrease after the release of the DXA Choosing Wisely recommendation. Targeted initiatives addressing providers with high ordering rates will be needed to change behavior. PMID- 26860500 TI - Proton pump inhibitors and fracture: they impair bone quality and increase fall risk? PMID- 26860501 TI - Intensity is a subjective construct. PMID- 26860502 TI - Mechanistic investigation of palladium-catalyzed amidation of aryl halides. AB - A mechanistic investigation using Becke3LYP density functional theory (DFT) was carried out on the palladium-catalyzed amidition of bromobenzene and (t)Bu isocyanide. The whole catalytic cycle consists of five steps: oxidative addition, migratory insertion, anion exchange, reductive elimination, and hydrogen migration. The rate-determining step is oxidative addition, with a small Gibbs free energy of 14.6 kcal mol(-1). In the migratory insertion step, (t)Bu isocyanide provides an important source of carboxy and amino groups to establish the amide group. For anion exchange, path 1a is suggested as the most favorable pathway with the help of the base, and water provides a source of oxygen which is perfectly in line with experimental observations. Finally, in the hydrogen migration step, we illustrate that the six-membered ring path is energetically favored due to the assisting influence of water. In addition, our calculations indicate that using dimethyl sulfoxide as a solvent does not change the rate determining step. PMID- 26860503 TI - Probing the ATP-induced conformational flexibility of the PcrA helicase protein using molecular dynamics simulation. AB - Helicases are enzymes that unwind double-stranded DNA (dsDNA) into its single stranded components. It is important to understand the binding and unbinding of ATP from the active sites of helicases, as this knowledge can be used to elucidate the functionality of helicases during the unwinding of dsDNA. In this work, we investigated the unbinding of ATP and its effect on the active-site residues of the helicase PcrA using molecular dynamic simulations. To mimic the unbinding process of ATP from the active site of the helicase, we simulated the application of an external force that pulls ATP from the active site and computed the free-energy change during this process. We estimated an energy cost of ~85 kJ/mol for the transformation of the helicase from the ATP-bound state (1QHH) to the ATP-free state (1PJR). Unbinding led to conformational changes in the residues of the protein at the active site. Some of the residues at the ATP binding site were significantly reoriented when the ATP was pulled. We observed a clear competition between reorientation of the residues and energy stabilization by hydrogen bonds between the ATP and active-site residues. We also checked the flexibility of the PcrA protein using a principal component analysis of domain motion. We found that the ATP-free state of the helicase is more flexible than the ATP-bound state. PMID- 26860506 TI - Individualized Food-Based Dietary Therapy for Crohn's Disease: Are We Making Progress? PMID- 26860507 TI - Gastroenterology Training in Japan. PMID- 26860504 TI - Strain-Related Differences in the Immune Response: Relevance to Human Stroke. AB - There are significant differences in the immune response and in the susceptibility to autoimmune diseases among rodent strains. It would thus be expected that the contribution of the immune response to cerebral ischemic injury would also differ among rodent strains. More importantly, there are significant differences between the immune responses of rodents and humans. All of these factors are likely to impact the successful translation of immunomodulatory therapies from experimental rodent models to patients with stroke. PMID- 26860508 TI - Opportunities for Improvement in the Care of Patients Hospitalized for Inflammatory Bowel Disease-Related Colitis. AB - BACKGROUND: Algorithms for the diagnosis, management, and follow-up have been proposed for patients hospitalized for inflammatory bowel disease (IBD) colitis flare. The degree to which providers adhere to these algorithms is unknown. This study evaluated the quality of care in IBD patients hospitalized for disease associated exacerbations and factors correlated with higher degrees of care. METHODS: Retrospective chart review of 34 patients during 60 admissions to the medicine service for IBD colitis exacerbation between 2005 and 2012 at the Veterans Affairs San Diego Medical Center. Examined factors included laboratory testing, timing of consultation and intravenous steroids, abdominal imaging, endoscopic examination, venous thromboembolism (VTE) prophylaxis, narcotic use, Clostridium difficile and cytomegalovirus testing, symptomatology at discharge, timing of follow-up, and rates of readmission and mortality. RESULTS: Quality of care varied among the factors studied, ranging from 30.5 % for pharmacologic VTE prophylaxis to 84.7 % for gastroenterology consultation within 24 h. Of 60 admissions, 22 % were not tested for C. difficile. Fifteen percent of patients were discharged before meeting commonly used discharge criteria. Eighty percent were seen in clinic at any time post-discharge; 6.7 % were readmitted; 10 % were lost to follow-up; 1.7 % opted for outside follow-up; and 1.7 % expired. CONCLUSIONS: The quality of care for patients admitted with IBD colitis flares is variable. These data outline opportunities for improvement, particularly in regard to pain management, VTE prophylaxis, and follow-up. Further studies are needed to test intervention strategies for practice improvement. PMID- 26860511 TI - Radiofrequency Ablation of Cameron Lesions. PMID- 26860509 TI - Dual Alpha2C/5HT1A Receptor Agonist Allyphenyline Induces Gastroprotection and Inhibits Fundic and Colonic Contractility. AB - BACKGROUND: Allyphenyline, a novel alpha2-adrenoceptor (AR) ligand, has been shown to selectively activate alpha2C-adrenoceptors (AR) and 5HT1A receptors, but also to behave as a neutral antagonist of alpha2A-ARs. We exploited this unique pharmacological profile to analyze the role of alpha2C-ARs and 5HT1A receptors in the regulation of gastric mucosal integrity and gastrointestinal motility. METHODS: Gastric injury was induced by acidified ethanol in Wistar rats. Mucosal catalase and superoxide dismutase levels were measured by assay kits. The effect of allyphenyline on electrical field stimulation (EFS)-induced fundic and colonic contractions was determined in C57BL/6 mice. RESULTS: Intracerebroventricularly injected allyphenyline (3 and 15 nmol/rat) dose dependently inhibited the development of mucosal damage, which was antagonized by ARC 239 (alpha2B/C-AR and 5HT1A receptor antagonist), (S)-WAY 100135 (selective 5HT1A receptor antagonist), and JP-1302 (selective alpha2C-AR antagonist). This protection was accompanied by significant elevation of mucosal catalase and superoxide dismutase levels. Allyphenyline (10(-9)-10(-5) M) also inhibited EFS-induced fundic contractions, which was antagonized by ARC 239 and (S)-WAY 100135, but not by JP-1302. Similar inhibition was observed in the colon; however, in this case only ARC 239 reduced this effect, while neither selective inhibition of alpha2C-ARs and 5HT1A receptors nor genetic deletion of alpha2A- and alpha2B-ARs influenced it. CONCLUSIONS: Activation of both central alpha2C-ARs and 5HT1A receptors contributes to the gastroprotective action of allyphenyline in rats. Its inhibitory effect on fundic contractions is mediated by 5HT1A receptors, but neither alpha2-ARs nor 5HT1A receptors take part in its inhibitory effect on colonic contractility in mice. PMID- 26860510 TI - Involvement of Transient Receptor Potential Vanilloid Receptor 1, (TRPV1) Expressing Vagal Nerve in the Inhibitory Effect of Gastric Acidification on Exogenous Motilin-Induced Gastric Phase III Contractions in Suncus murinus. AB - BACKGROUND: Gastric acidification inhibits motilin-induced gastric phase III contractions. However, the underlying mechanism has not been thoroughly investigated. Here, we studied the inhibitory mechanism by gastric acidification on motilin-induced contraction in Suncus murinus (S. murinus). METHODS: We measured interdigestive gastric phase III contractions in conscious, freely moving S. murinus, and examined the inhibitory effect of gastric acidification on motilin action and the involvement of the vagus nerve and transient receptor potential vanilloid receptor 1 (TRPV1) in the inhibitory mechanism. RESULTS: A bolus injection of motilin evoked phase III-like contractions during intravenous infusion of saline. Intragastric acidification (pH 1.5-2.5) inhibited motilin induced phase III contractions in a pH-dependent manner and significantly decreased the motility index at a pH below 2.0. In contrast, intraduodenal acidification (pH 2.0) failed to inhibit motilin-induced contractions. Vagotomy significantly alleviated the suppression of motilin-induced gastric contractions under acidic conditions (pH 2.0), suggesting vagus nerve involvement. Moreover, intragastric acidification (pH 2.0) significantly increased the number of c-Fos positive cells in the nucleus tractus solitarii. In vagotomized S. murinus, the number of c-Fos-positive cells did not change, even under gastric acidification conditions. TRPV1 mRNA was highly expressed in the muscle and mucosal regions of the antrum and the nodose ganglion, whereas was not detected in the upper small intestine. Capsazepin, a TRPV1 antagonist, completely rescued the inhibitory effect of gastric acidification. CONCLUSIONS: Gastric acidification in S. murinus inhibits motilin-induced contractions, a finding similar to results observed in humans, while TRPV1-expressing vagus nerves play a role in the inhibitory mechanism. PMID- 26860512 TI - SEMS for Palliation of Malignant Colonic Obstruction: Why SEMi Available Is Not Good Enough. PMID- 26860513 TI - Association of primary aldosteronism with chronic thyroiditis. PMID- 26860514 TI - Mediterranean diet cools down the inflammatory milieu in type 2 diabetes: the MEDITA randomized controlled trial. AB - Mediterranean-style diets provide cardiovascular benefits and increase insulin sensitivity. There is little evidence that adherence to Mediterranean diet may influence the levels of the inflammatory milieu in type 2 diabetes. The aim of this study was to assess whether Mediterranean diet influences both C-reactive protein (CRP) and adiponectin in newly diagnosed type 2 diabetes, and whether adherence to Mediterranean diet affects their circulating levels. In a two-arm, single-center trial, 215 men and women with newly diagnosed type 2 diabetes were randomized to a Mediterranean diet (n = 108, 54 males and 54 females) or a low fat diet (n = 107, 52 males and 55 females), with a total follow-up of 8.1 years. At baseline visit and at 1 year, body weight, HOMA index, CRP, and adiponectin and its fractions were assessed. Adherence to the diets was assessed by calculating the Mediterranean-diet score. At 1 year, CPR fell by 37 % and adiponectin rose by 43 % in the Mediterranean diet group, while remaining unchanged in the low-fat diet group. The pattern of adiponectin fractions (high and non-high molecular weight) showed a response similar to that of total adiponectin. Diabetic patients with the highest scores (6-9 points) of adherence to Mediterranean diet had lower circulating CRP level and higher circulating total adiponectin levels than the diabetic patients who scored <3 points on the scale (P = 0.001). The results of this randomized controlled trial demonstrate that Mediterranean diet cools down the inflammatory milieu of type 2 diabetes. PMID- 26860515 TI - Blood glucose fluctuation accelerates renal injury involved to inhibit the AKT signaling pathway in diabetic rats. AB - Blood glucose fluctuation is associated with diabetic nephropathy. However, the mechanism by which blood glucose fluctuation accelerates renal injury is not fully understood. The aim of the present study was to assess the effects of blood glucose fluctuation on diabetic nephropathy in rats and investigate its underlying mechanism. Diabetes in the rats was induced by a high sugar, high-fat diet, and a single dose of STZ (35 mg/kg)-injected intraperitoneally. Unstable blood sugar models were induced by subcutaneous insulin injection and intravenous glucose injection alternately. Body weight, glycosylated hemoglobin A1c (HbAlc), blood urea nitrogen (BUN), serum creatinine (Scr), and Creatinine clearance (Ccr) were assessed. T-SOD activity and MDA level were measured by assay kit. Change in renal tissue ultrastructure was observed by light microscopy and electron microscopy. Phosphorylated ser/thr protein kinase (p-AKT) (phosphor-Ser473), phosphorylated glycogen synthase kinase-3 beta (p-GSK-3beta) (phosphor-Ser9), Bcl 2-associated X protein (BAX), B cell lymphoma/leukemia 2 (BCL-2), and cleaved cysteinyl aspartate-specific proteinase-3 (caspase-3) levels were detected by immunohistochemistry and Western blot. We observed that BUN and Scr were increased in diabetic rats, and Ccr was decreased. Furthermore, blood glucose fluctuations could exacerbate the Ccr changes. Renal tissue ultrastructure was also seriously injured by glucose variability in diabetic rats. In addition, glucose fluctuation increased the oxidative stress of renal tissue. Moreover, fluctuating blood glucose decreased p-AKT level and BCL-2, and increased p-GSK 3beta, BAX, cleaved-caspase-3 levels, and ratio of BAX/BCL-2 in the kidneys of diabetic rats. In conclusion, these results suggest that blood glucose fluctuation accelerated renal injury is due, at least in part to its oxidative stress promoting and inhibiting the AKT signaling pathway in diabetic rats. PMID- 26860516 TI - Electrocardiographic and scintigraphic evaluation of patients with subclinical hyperthyroidism during workout. AB - Subclinical hyperthyroidism (sHT) was found to be associated with elevated heart rate, blood pressure and increased risk of extrasystoles. However, the full clinical relevance of morphological and functional implications of sHT on the cardiovascular system is still a matter of debate. The aim of the study was to prospectively assess the influence of endogenous sHT on exercise capacity and cardiac function during workout with the use of exercise electrocardiography (ExECG) and perfusion scintigraphy. The studied group consisted of 44 consecutively recruited patients diagnosed with sHT. In all patients, ExECG, followed by post-exercise myocardial perfusion imaging, was performed. Both ExECG and scintigraphy were performed twice-in the state of sHT and after euthyroidism was restored. An average time period of exercise test was significantly longer in the state of euthyroidism than in sHT. An average oxygen consumption during exercise test was also higher after euthyroidism was achieved when compared to sHT. The end-diastolic and end-systolic volume indexes, stroke volume index and cardiac index were significantly larger in patients with sHT if compared values achieved after euthyroidism restoration. Stroke volume index was negatively correlated with TSH, and positively with free thyroid hormones values in the state of sHT, before euthyroidism was achieved. Cardiac index was positively correlated with free thyroid hormones levels. The obtained results indicate worse physical capacity in subjects with sHT and improvement of several parameters assessed during ExECG and perfusion scintiscan after therapy. Observed changes might reflect the mechanism of the deleterious effect exerted by sHT on the heart. PMID- 26860517 TI - Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome. AB - This study aimed to detect serum microRNAs (miRNAs) differentially expressed between polycystic ovary syndrome (PCOS) patients with impaired glucose metabolism (IGM), PCOS patients with normal glucose tolerance (NGT), and healthy controls. A TaqMan miRNA array explored serum miRNA profiles as a pilot study, then selected miRNAs were analyzed in a validation cohort consisting of 65 PCOS women with IGM, 65 PCOS women with NGT, and 45 healthy women The relative expression of miR-122, miR-193b, and miR-194 was up-regulated in PCOS patients compared with controls, whereas that of miR-199b-5p was down-regulated. Furthermore, miR-122, miR-193b, and miR-194 were increased in the PCOS-IGM group compared with the PCOS-NGT group. Multiple linear regression analyses revealed that miR-193b and body mass index contributed independently to explain 43.7 % (P < 0.0001) of homeostasis model assessment-insulin resistance after adjustment for age. Investigation of diagnostic values confirmed the optimal combination of BMI and miR-193b to explore the possibility of IGM in PCOS women with area under the curve of 0.752 (95 % CI 0.667-0.837, P < 0.001). Bioinformatics analysis indicated that the predicted target functions of these miRNAs mainly involved glycometabolism and ovarian follicle development pathways, including the insulin signaling pathway, the neurotrophin signaling pathway, the PI3K-AKT signaling pathway, and regulation of actin cytoskeleton. This study expands our knowledge of the serum miRNA expression profiles of PCOS patients with IGM and the predicted target signal pathways involved in disease pathophysiology. PMID- 26860518 TI - Diagnosis of turner syndrome in two mothers following their daughters' diagnosis. PMID- 26860520 TI - Developing resilience: Stories from novice nurse academics. AB - BACKGROUND: It is acknowledged that novice nurse academics face many challenges on commencement of their new role. Most are recruited from the clinical arena, with little understanding of the academic triumvirate of teaching, research and service. They struggle with role expectation and experience feelings of isolation and anxiety. AIM: The aim of this paper is to report on an exploration of 14 new nurse academics from two major nursing education institutions as they utilised and developed resilience building strategies. METHOD: The paper is drawn from a qualitative study that sought to see the world through the eyes of the participants through storytelling. Data was collected using semi-structured, conversational style interviews. Interviews were audio recorded and revealed themes that captured resilience strategies. RESULTS: These themes were: Developing supportive collegial relationships; Embracing positivity; and Reflection and transformative growth. The first theme, developing supportive relationships, provides insight into the mentoring process and the relationships developed with peers and colleagues. The second theme, embracing positivity, describes the factors that assisted them to face the adversity and challenges in the new role. The final theme, reflection and transformative growth, demonstrated participants' reflecting on difficult situations and demonstrating the ability to learn from the experiences and move forward. CONCLUSIONS: The strategies utilised by the participants in this study were key factors in the development of resilience which assisted in the transition from clinical nurse to academic. These strategies were often tacit and it is imperative that in a time of acute nurse academic shortages where retention is paramount, that employing organisations support employees and contribute to resilience development. Education on resilience building strategies is fundamental for all new academics and is essential in the transition from clinical nurse to academic. PMID- 26860519 TI - The assessment of serum-mediated phagocytosis of necrotic material by polymorphonuclear leukocytes to diagnose and predict the clinical features of systemic lupus erythematosus: an observational longitudinal study. AB - BACKGROUND: Serum-mediated phagocytosis of antibody- and complement-opsonized necrotic cell material (NCM) by polymorphonuclear leukocytes can be quantified by using a flow cytometry-based assay. The phagocytosis of necrotic cell material (PNC) assay parallels the well-known lupus erythematosus cell test. In this study, we aimed to investigate the diagnostic accuracy of the assay and the relationship with clinical manifestations and disease activity in systemic lupus erythematosus (SLE). METHODS: The diagnostic accuracy for SLE diagnosis of the PNC assay was studied by cross-sectional assessment of blood samples from 148 healthy control subjects and a multicenter rheumatic group (MRG) of 529 patients with different rheumatic symptoms. A cohort of 69 patients with an established SLE diagnosis (SLE cohort) underwent longitudinal clinical and laboratory follow up for analysis of the temporal relationships between PNC positivity and specific clinical manifestations. RESULTS: In 35 of 529 MRG patients, 13 of whom had SLE, the PNC assay result was positive. Combined positivity of the PNC assay and anti double-stranded DNA antibodies increased specificity and positive predictive value for SLE diagnosis to 0.99 and 0.67, respectively. In the longitudinal study, 42 of 69 SLE cohort patients had positive results in the PNC assay at least once. PNC assay positivity was associated with current hematological manifestations and could predict mucocutaneous manifestations. When combined with hypocomplementemia, PNC positivity preceded increased Systemic Lupus Erythematosus Disease Activity Index 2000 score, glomerulonephritis, and alopecia. CONCLUSIONS: Serum-mediated PNC by polymorphonuclear leukocytes is commonly but not exclusively seen in patients with SLE. The PNC assay may be used in follow-up of patients with SLE and, especially in combination with other routinely assessed laboratory tests, may help to predict flares and different clinical manifestations, including glomerulonephritis. Our results encourage further development of the PNC assay as a complementary laboratory tool in management of patients with SLE. PMID- 26860521 TI - Learning how to learn: Meta-learning strategies for the challenges of learning pharmacology. AB - BACKGROUND: Nursing students have difficulty with pharmacology courses because of the complicated nomenclature and the difficulty of applying drug information to actual patient care. OBJECTIVES: As part of a new pharmacology course being created, meta-learning strategies designed to diminish the difficulties of learning this difficult content were part of the course pedagogy. DESIGN: Strategies were demonstrated, reviewed in class, and implemented through homework assignments. SETTING: The setting was an Academic Health Center's School of Nursing in the southern United States. PARTICIPANTS: Participants were third-year nursing students in an undergraduate nursing program. METHODS: Surveys of students' opinions of learning gains were conducted at the end of the course over several semesters. In addition, pharmacology scores on a standardized exit exam were compared prior to implementing the course and after. RESULTS: Students reported learning dry material more easily, having greater confidence, and finding substantial value in the learning strategies. Students indicated the most helpful strategies, in descending order, as follows: making charts to compare and contrast drugs and drug classes, writing out drug flash cards, making or reviewing creative projects, prioritizing information, making or using visual study aids, and using time and repetition to space learning. Implementation of the new course improved pharmacology scores on a standardized exit exam from 67.0% to 74.3%. CONCLUSIONS: Overall response to learning strategies was positive, and the increase in the pharmacology standardized exit exam scores demonstrated the effectiveness of this instructional approach. PMID- 26860524 TI - Characterization of T1 bias in skeletal muscle from fat in MOLLI and SASHA pulse sequences: Quantitative fat-fraction imaging with T1 mapping. AB - PURPOSE: To characterize the effects of fat on commonly used T1 mapping sequences and evaluate a new method of quantitative fat fraction (FF) imaging for low fractions based on the modulation of T1 values by the fat pool. METHODS: Bloch equation simulations and phantom and in vivo (skeletal muscle) experiments were used to characterize the response of the modified Look-Locker inversion recovery (MOLLI) and saturation recovery single-shot acquisition (SASHA) T1 mapping sequences to fat-water systems with known FFs (0%-10%) at 1.5T. FFs were measured with single voxel spectroscopy and Dixon imaging methods. A new T1 -based FF imaging method was evaluated using Monte Carlo simulations and phantom and in vivo experiments. RESULTS: SASHA and MOLLI had similar T1 dependence on FF, with characteristic under- or overestimation of T1 values as a function of off resonance frequency (30-70 ms variation in native T1 per 1% FF). FF maps generated from the SASHA method yielded a low variability of +/-0.25% for a signal-to-noise ratio of 150:1 in the nonsaturation image, with good agreement with spectroscopy and a performance that is superior to that of Dixon methods at low FFs. CONCLUSION: Fat results in negative or positive shifts in native tissue T1 measured with MOLLI and SASHA over a narrow range of off-resonance frequencies; T1 shifts from fat can be used to accurately quantify FF. Magn Reson Med 77:237-249, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26860522 TI - Proprioceptive ability at the lips and jaw measured using the same psychophysical discrimination task. AB - In the human face, the muscles and joints that generate movement have different properties. Whereas the jaw is a conventional condyle joint, the facial musculature has neither distinct origin nor insertion points, and the muscles do not contain muscle spindle proprioceptors. This current study aims to compare the proprioceptive ability at the orofacial muscles with that of the temporomandibular joint (TMJ) in 21 neuro-typical people aged between 18 and 65 years. A novel psychophysical task was devised for use with both structures that involved a fixed 30.5 mm start separation followed by closure onto stimuli of 5, 6, 7, 8 mm diameter. The mean proprioceptive score when using the lips was 0.84 compared to 0.79 at the jaw (p < 0.001), and response error was lower by 0.1 mm. The greater accuracy in discrimination of lip movement is significant because, unlike the muscles controlling the TMJ, the orbicularis oris muscle controlling the lips inserts on to connective tissue and other muscle, and contains no muscle spindles, implying a different more effective, proprioceptive mechanism. Additionally, unlike the lack of correlation previously observed between joints in the upper and lower limbs, at the face the scores from performing the task with the two different structures were significantly correlated (r = 0.5, p = 0.018). These data extend the understanding of proprioception being correlated for the same left and right joints and correlated within the same structure (e.g. ankle dorsiflexion and inversion), to include use-dependant proprioception, with performance in different structures being correlated through extended coordinated use. At the lips and jaw, it is likely that this arises from extensive coordinated use. This informs clinical assessment and suggests a potential for coordinated post-injury training of the lips and jaw, as well as having the potential to predict premorbid function via measurement of the uninjured structure, when monitoring progress and setting clinical rehabilitation goals. PMID- 26860525 TI - Screening of Phenolic Compounds Reveals Inhibitory Activity of Nordihydroguaiaretic Acid Against Three Enzymes Involved in the Regulation of Blood Glucose Level. AB - In this work we have focused on the inhibition of three different enzymes with a role in postprandial glucose management: alpha-amylase, alpha-glucosidase and dipeptidyl peptidase 4. The assortment of 29 monomeric phenolic compounds was first screened at a single concentration. Next, the IC50 values of tested compounds were evaluated for compounds that considerably inhibited any of the enzymes. Nordihydroguaiaretic acid, a phenolic compound abundant in Creosote bush Larrea tridentata, possessed inhibitory activity for all tested enzymes. This in vitro mechanism of action supports traditional use of Creosote bush in diabetes treatment. PMID- 26860526 TI - Chelating Properties of Peptides from Red Seaweed Pyropia columbina and Its Effect on Iron Bio-Accessibility. AB - The aim of this work was to evaluate copper-chelating, iron-chelating and anticariogenic activity of peptides obtained by enzymatic hydrolysis of P. columbina protein concentrate and to study the effects of chelating peptides on iron bio-accessibility. Two hydrolyzates were obtained from P. columbina protein concentrate (PC) using two hydrolysis systems: alkaline protease (A) and alkaline protease + Flavourzyme (AF). FPLC gel filtration profile of PC shows a peak having molecular weight (MW) higher than 7000 Da (proteins). A and AF hydrolyzates had peptides with medium and low MW (1013 and 270 Da), respectively. Additionally, AF presented free amino acids with MW around 82 Da and higher content of His and Ser. Peptides from AF showed the highest chelating properties measured as copper-chelating activity (the lowest beta-carotene oxidation rate: Ro; 0.7 min(-1)), iron-chelating activity (33%), and phosphorous and Ca(2+) release inhibition (87 and 81%, respectively). These properties could indicate antioxidant properties, promotion of iron absorption and anticariogenic activity, respectively. In fact, hydrolyzates promoted iron dialyzability (~ 16%), values being higher than that found for P. columbina seaweed. Chelating peptides from both hydrolyzates can maintain the iron in a soluble and bio-accessible form after gastrointestinal digestion. PMID- 26860527 TI - Traumatic myopia secondary to ciliary spasm after blunt eye trauma and reconsideration of its pathogenesis. AB - PURPOSE: To reconsider the pathogenesis of traumatic myopia by describing two cases and literature review. METHODS: Refraction was measured, A-scan ultrasonography was performed, and ultrasound biomicroscopy (UBM) was used to observe the ciliary body in the acute and recovery stages. RESULTS: The first patient had a myopic shift of -6.12 diopters (D) on the initial examination (day 2) compared with the recovered stage. UBM showed ciliochoroidal effusion in one half of the circumference and severe edema in three eighths of the ciliary body, which led to an anterior rotation of the ciliary body. Immediately after the cycloplegia, the myopic shift decreased by -3.9 D. On day 11, the refraction was 0.63 D, and the UBM findings were normalized. The second patient had a myopic shift of -4.38 D on the first examination compared with the recovered stage. UBM showed an annular ciliochoroidal effusion leading to anterior rotation of the ciliary body. Immediately after the cycloplegia, there was a decrease of -2.75 D. Biometric measurements showed an increased anterior chamber depth and a decreased thickness of the lens. On day 16, the refraction was -1.0 D, and the UBM findings were normalized. In both cases, biometric measurements in the acute phase suggested a anterior chamber shallowing, a thickening of the lens, and an anterior shift of the lens-iris diaphragm CONCLUSIONS: Cycloplegia decreased the myopic shift by more than 60 %. These findings indicate a significant contribution of ciliary spasm combined with ciliochoroidal effusion, anterior shift of the lens-iris diaphragm, and thickening of the lens. PMID- 26860528 TI - Chemodenervation of extraocular muscles with botulinum toxin in thyroid eye disease. AB - BACKGROUND: Thyroid eye disease (TED) presents a management dilemma for strabismologists due to the variability of its clinical course. Prisms may be prescribed to relieve diplopia in small deviations. Surgical intervention, on the other hand, should not be done until the active phase of the disease has subsided. We report our experience with chemodenervation utilizing botulinum toxin (BT) injection in the management of TED-related strabismus. METHODS: A retrospective chart review was done on twenty-two (22) consecutive patients receiving BT injections at the University of California, San Diego (UCSD) Thyroid Eye Center. All BT injections were administered by a single physician under electromyographic guidance. RESULTS: The clinical records of 22 patients (18 females) were reviewed. Seven patients (32 %) had a reduction of their deviation to a point where surgery was not required. In six patients (27 %), surgery was required but an improvement in ocular deviation was found, altering the original surgical plan. In four patients (18 %), the deviation continued to progress after BT injection. Success rates were higher if pre-treatment deviation was less than 20 prism diopters ((?)). CONCLUSION: One third of the chemodenervation-treated patients avoided surgical intervention, with an additional 27 % (total of 40 % of those who needed surgery) having a reduced deviation prior to surgery. Using BT injection to extraocular muscles to treat diplopia in TED patients is most effective in preventing surgery in those patients with 20(?) or less of deviation. PMID- 26860529 TI - Factors associated with the specific worries of childhood cancer survivors: Cross sectional survey in Japan. AB - BACKGROUND: Previous research has shown that adult childhood cancer survivors (CCS) have many worries. We re-analyzed the employment data in order to identify these worries and their associated factors. METHODS: The participants were selected from the membership directory of Heart Link mutual-aid health insurance, and recruited by the CCS Network. We conducted a cross-sectional survey (a self rated questionnaire on employment) via post or email with a link to an Internet website. We investigated the association between CCS factors and the specific worries. The adjusted odds ratios (OR) for the associated factors with a specific worry were estimated on logistic regression analysis. RESULTS: A total of 240 questionnaires were collected by November 2012. One questionnaire was excluded because the answers were not provided by the CCS him/herself. The most common worries were health-related problems (50%) and employment issues (40%), which were followed by his/her personality and life (23%) and self-appearance (20%). Fifty (21%) out of 239 CCS answered no specific worry. The common consistent factor associated with worries was the presence of late effects. Of note was that the CCS worries were not associated with age at diagnosis or follow up, gender, educational achievement or marriage. The worry about employment issues was associated with economic status, disability qualification, and employment status. CONCLUSIONS: The CCS worries were strongly affected by the presence of late effects. No significant association was noted between CCS worries and gender, age at diagnosis or follow up, or educational achievements. Economic status and disability qualification were associated with some worries. PMID- 26860531 TI - Elastic Frustration Causing Two-Step and Multistep Transitions in Spin-Crossover Solids: Emergence of Complex Antiferroelastic Structures. AB - Two-step and multistep spin transitions are frequently observed in switchable cooperative molecular solids. They present the advantage to open the way for three- or several-bit electronics. Despite extensive experimental studies, their theoretical description was to date only phenomenological, based on Ising models including competing ferro- and antiferro-magnetic interactions, even though it is recognized that the elastic interactions are at the heart of the spin transition phenomenon, due to the volume change between the low- and high-temperature phases. To remedy this shortcoming, we designed the first consistent elastic model, taking into account both volume change upon spin transition and elastic frustration. This ingredient was revealed to be powerful, since it was able to obtain all observed experimental configurations in a consistent way. Thus, according to the strength of the elastic frustration, the system may undergo first-order transition with hysteresis, gradual, hysteretic two-step or multistep transitions, and incomplete transitions. Furthermore, the analysis of the spatial organization of the HS and LS species in the plateau regions revealed the emergence of complex antiferro-elastic patterns going from simple antiferro magnetic-like order to long-range spatial modulations of the high-spin fraction. These results enabled us to identify the elastic frustration as the fundamental mechanism at the origin of the very recent experimental observations showing the existence of organized spatial modulations of the high-spin fraction inside the plateau of two-step spin transitions. PMID- 26860530 TI - Is there a relationship between spinal instability in neoplastic disease and Tokuhashi scoring system? AB - Spinal instability neoplastic score (SINS) classification evaluates spinal stability by adding together six radiographic and clinical components. The objective of this study was to verify the association between SINS and Tokuhashi scoring system (TSS) score. Fifty-eight patients with vertebral metastases were admitted from 2010 to 2014 at Hospital do Servidor Publico Estadual de Sao Paulo. They were evaluated according to their SINS and Tokuhashi SS score. Fourteen patients (24.13 %) scored from 0 to 6 points (stable spine), 37 (63.79 %) scored from 7 to 12 (potentially unstable), and 7 (12.06 %) scored from 13 to 18 (unstable). In stable spine patients according to SINS, the mean TSS score was 9.2. In potentially unstable spine patients, the mean TSS score was 8.24. In unstable spine patients, mean TSS score was 6.28. There was a statistically significant difference of the TSS score between stable and unstable patients. After evaluating TSS score in each patient, the worse the SINS, the worse was also the TSS score. PMID- 26860532 TI - The effects of physical contact type on the internal and external demands during a rugby league match simulation protocol. AB - The aim of this study was to investigate how the type of contact influences physiological, perceptual and locomotive load during a simulated rugby league match. Eleven male university rugby league players performed two trials of the rugby league movement simulation protocol for interchange forwards with a traditional soft tackle bag and a weighted tackle sled to replicate contact demands. The interchange forward-specific simulation was chosen given the contact frequency is higher for this group of players compared to whole match players. Locomotive rate, sprint speed, tackle intensity, heart rate (HR) and rating of perceived exertion were analysed during the first and second bouts that replicated two ~23 min on-field passages. Countermovement jump (CMJ) was measured before and immediately after each trial. More time was spent in heart rate zone between 91 and 100% HRpeak during the first (effect size +/- 90% confidence interval: 0.44 +/- 0.49) and second bouts (0.44 +/- 0.43), and larger (0.6 +/- 0.69) decrements in CMJ performance were observed during the sled trial (5.9, s = 4.9%) compared to the bag trial (2.6, s = 5.4%). Changing the type of contact during the match simulation subtly altered both the internal and external loads on participants. Using a standard tackle bag results in faster sprint speed to contact, but lower overall high-intensity running. Conversely, a heavier tackle object increases the internal load and results in greater lower limb neuromuscular fatigue as reflected by the decrease in CMJ performance. PMID- 26860533 TI - Increased analgesia administration in emergency medicine after implementation of revised guidelines. AB - BACKGROUND: The most common complaint of patients attending the emergency department (ED) is pain, caused by different diseases. Yet the treatment of pain at the ED is suboptimal, and oligoanalgesia remains common. The objective of this study is to determine whether the administration of analgesia at the ED increases by implementation of revised guidelines in pain management. METHODS: We conducted a prospective pre-post intervention cohort study with implementation of a revised guideline for pain management at our ED, in which nurses are allowed to administer analgesia (including low-dosage piritramid (opioid) intravenous) without doctor intervention. Numeric Rating Scales (NRS) were measured, and administration of medication (main outcome) was documented. We included every adult patient presenting with pain (NRS 4-10) at the ED. RESULTS: A total of 2107 patients (1089 pre-implementation phase and 1018 post-implementation phase) were included in our study. During pre-implementation, 25.4 % of the patients with NRS between 4 and 10 received analgesia. After implementation, 32.0 % of these patients received analgesia (p < 0.001). CONCLUSIONS: After implementation of the revised guidelines in pain management at the ED, the administration of pain medication increased significantly. Nevertheless, the percentage of patients in pain receiving analgesia remain low (32 % after implementation). PMID- 26860535 TI - Does the Theory of Planned Behaviour Explain Condom Use Behaviour Among Men Who have Sex with Men? A Meta-analytic Review of the Literature. AB - The aim of this meta-analysis was to explore whether the constructs in the theory of planned behaviour (TPB; i.e., attitude, subjective norm, perceived behavioural control, intention) explain condom use behaviour among men who have sex with men (MSM). Electronic databases were searched for studies that measured TPB variables and MSM condom use. Correlations were meta-analysed using a random effects model and path analyses. Moderation analyses were conducted for the time frame of the behavioural measure used (retrospective versus prospective). Attitude, subjective norm and perceived behavioural control accounted for 24.0 % of the variance in condom use intention and were all significant correlates. Intention and PBC accounted for 12.4 % of the variance in condom use behaviour. However, after taking intention into account, PBC was no longer significantly associated with condom use. The strength of construct relationships did not differ between retrospective and prospective behavioural assessments. The medium to large effect sizes of the relationships between the constructs in the TPB, which are consistent with previous meta-analyses with different behaviours or target groups, suggest that the TPB is also a useful model for explaining condom use behaviour among MSM. However, the research in this area is rather small, and greater clarity over moderating factors can only be achieved when the literature expands. PMID- 26860534 TI - Evolutionary patterns of Toll-like receptor signaling pathway genes in the Suidae. AB - BACKGROUND: The Toll-like receptor (TLR) signaling pathway constitutes an essential component of the innate immune system. Highly conserved proteins, indicative of their critical roles in host survival, characterize this pathway. Selective constraints could vary depending on the gene's position within the pathway as TLR signaling is a sequential process and that genes downstream of the TLRs may be more selectively constrained to ensure efficient immune responses given the important role of downstream genes in the signaling process. Thus, we investigated whether gene position influenced protein evolution in the TLR signaling pathway of the Suidae. The members of the Suidae examined included the European Sus scrofa (wild boar), Asian Sus scrofa (wild boar), Sus verrucosus, Sus celebensis, Sus scebifrons, Sus barbatus, Babyrousa babyrussa, Potamochoerus larvatus, Potamochoerus porcus and Phacochoerus africanus. RESULTS: A total of 33 TLR signaling pathway genes in the Suidae were retrieved from resequencing data. The evolutionary parameter omega (dn/ds) had an overall mean of 0.1668 across genes, indicating high functional conservation within the TLR signaling pathway. A significant relationship was inferred for the network parameters gene position, number of protein-protein interactions, protein length and the evolutionary parameter dn (nonsynonymous substitutions) such that downstream genes had lower nonsynonymous substitution rates, more interactors and shorter protein length than upstream genes. Gene position was significantly correlated with the number of protein-protein interactions and protein length. Thus, the polarity in the selective constraint along the TLR signaling pathway was due to the number of molecules a protein interacted with and the protein's length. CONCLUSION: Results indicate that the level of selective constraints on genes within the TLR signaling pathway of the Suidae is dependent on the gene's position and network parameters. In particular, downstream genes evolve more slowly as a result of being highly connected and having shorter protein lengths. These findings highlight the critical role of gene network parameters in gene evolution. PMID- 26860537 TI - Mixing Online and Face-to-Face Therapy: How to Benefit From Blended Care in Mental Health Care. AB - Blended care, a combination of online and face-to-face therapy, is increasingly being applied in mental health care to obtain optimal benefit from the advantages these two treatment modalities have. Promising results have been reported, but a variety in descriptions and ways of operationalizing blended care exists. Currently, what type of "blend" works for whom, and why, is unclear. Furthermore, a rationale for setting up blended care is often lacking. In this viewpoint paper, we describe postulates for blended care and provide an instrument (Fit for Blended Care) that aims to assist therapists and patients whether and how to set up blended care treatment. A review of the literature, two focus groups (n=5 and n=5), interviews with therapists (n=14), and interviews with clients (n=2) were conducted to develop postulates of eHealth and blended care and an instrument to assist therapists and clients in setting up optimal blended care. Important postulates for blended care are the notion that both treatment modalities should complement each other and that set up of blended treatment should be based on shared decision making between patient and therapist. The "Fit for Blended Care" instrument is presented which addresses the following relevant themes: possible barriers to receiving blended treatment such as the risk of crisis, issues in communication (at a distance), as well as possible facilitators such as social support. More research into the reasons why and for whom blended care works is needed. To benefit from blended care, face-to-face and online care should be combined in such way that the potentials of both treatment modalities are used optimally, depending on patient abilities, needs, and preferences. To facilitate the process of setting up a personalized blended treatment, the Fit for Blended Care instrument can be used. By applying this approach in research and practice, more insight into the working mechanisms and optimal (personal) "blends" of online and face-to-face therapy becomes within reach. PMID- 26860536 TI - A Comparison of Five Brief Screening Tools for HIV-Associated Neurocognitive Disorders in the USA and South Africa. AB - Screening for HIV-associated neurocognitive disorders (HAND) is important to improve clinical outcomes. We compared the diagnostic sensitivity and specificity of the mini-mental state examination, International HIV dementia scale (IHDS), Montreal cognitive assessment, Simioni symptom questionnaire and cognitive assessment tool-rapid version (CAT-rapid) to a gold standard neuropsychological battery. Antiretroviral-experienced participants from Cape Town, South Africa, and Baltimore, USA, were recruited. The sensitivity and specificity of the five tools, as well as those of the combined IHDS and CAT-rapid, were established using 2 * 2 contingency tables and ROC analysis. More than a third (65165) had symptomatic HAND. In detecting HIV-D, the CAT-Rapid had good sensitivity (94 %) and weak specificity (52 %) (cut-point <=10), while the IHDS showed fair sensitivity (68 %) and good specificity (86 %) (cut-point <=10). The combined IHDS and CAT-rapid showed excellent sensitivity and specificity for HIV-D at a cut-off score of <=16 (out of 20; 89 and 82 %). No tool was adequate in screening for any HAND. The combination IHDS and CAT-rapid tool appears to be a good screener for HIV-D but is only fairly sensitive and poorly specific in screening for any HAND. Screening for milder forms of HAND continues to be a clinical challenge. PMID- 26860538 TI - Autophagy upregulation promotes macrophages to escape mesoporous silica nanoparticle (MSN)-induced NF-kappaB-dependent inflammation. AB - BACKGROUND: Our previous studies (Int J Nanomed 10:22, 2015) have indicated that a single large dose of mesoporous silica nanoparticles (MSNs) can induce severe and selective nephrotoxicity, which is closely related to inflammation mediated by the NF-kappaB pathway. However, the effect of MSNs on other organs and the interactions of nanomaterials with biological systems remain rudimentary. OBJECTIVE: This study aimed to clarify the biological behaviour and influence of MSNs on macrophages. METHODS: The mice received a single intraperitoneal injection of a suspension of 150, 300 of 600 mg/kg MSNs, and RAW 264.7 cells were treated with MSNs at various concentrations and times. Cell viability was determined by MTT assay and LDH release assay. The NF-kappaB pathway and the target proinflammatory cytokines IL-1beta and TNF-alpha were determined by western blotting or ELISA. Autophagy is considered as an emerging mechanism of nanomaterials. So the autophagic ultrastructural analysis, the determination of Beclin-1 and LC3 expression, and the calculation of LC3II dots were employed to verify autophagy activation. In addition, RNA interference, autophagy agonist and inhibitor were used to explore the role of autophagy in inflammation. RESULTS: The results indicated that MSNs are internalized into macrophages and induce cytotoxicity in a dose- and time-dependent manner. The NF-kappaB pathway, IL 1beta and TNF-alpha were induced and released by MSNs. The levels of Beclin-1 and LC3II dots were obviously up-regulated by MSNs, which indicated that autophagy was induced in the MSN-treated cells. Moreover, the enhanced autophagy can attenuate the inflammation mediated by the NF-kappaB pathway, whereas the inhibition of autophagy can contribute to inflammation. CONCLUSIONS: In summary, our results suggest that autophagy may be a possible protective factor in inflammation induced by MSNs in macrophages. PMID- 26860540 TI - Public opinions about supervised smoking facilities for crack cocaine and other stimulants. AB - BACKGROUND: The purpose of this study was to estimate awareness and opinions about supervised smoking facilities (SSFs) for smoking crack cocaine and other stimulants and make comparisons with awareness and opinions about supervised injection facilities (SIFs) in Ontario, Canada. METHODS: We used data from a 2009 telephone survey of a representative adult sample. The survey asked about awareness of, and level of support for, the implementation of SSFs and SIFs. Data were analysed using statistical models for complex survey data, which account for stratified sampling and incorporate sampling weights. RESULTS: A total of 1035 participated in the survey. Significantly fewer had knowledge about SSFs (17.9 %) than about SIFs (57.6 %). Fewer strongly agreed with implementation of SSFs (19.6 %) than SIFs (28.3 %). Just over half (51.1 %) of participants somewhat agreed or disagreed, 15.7 % strongly agreed, and 10.6 % strongly disagreed with implementing both SSFs and SIFs. CONCLUSIONS: Members of the public in Ontario had little knowledge of SSFs compared to SIFs. Recent federal government changes in Canada may provide the leadership environment necessary to ensure that innovative, evidence-based harm reduction programs such as SSFs are developed and implemented. PMID- 26860539 TI - Future directions in bladder cancer immunotherapy: towards adaptive immunity. AB - The clinical management of bladder cancer has not changed significantly in several decades. In particular, intravesical bacillus Calmette-Guerin (BCG) immunotherapy has been a mainstay for high-risk nonmuscle invasive bladder cancer since the late 1970s/early 1980s. This is despite the fact that bladder cancer has the highest recurrence rates of any cancer and BCG immunotherapy has not been shown to induce a tumor-specific immune response. We and others have hypothesized that immunotherapies capable of inducing tumor-specific adaptive immunity are needed to impact bladder cancer morbidity and mortality. This article summarizes the preclinical and clinical development of bladder cancer immunotherapies with an emphasis on the last 5 years. Expected progress in the near future is also discussed. PMID- 26860542 TI - Quality of Life of Patients with Advanced Chronic Kidney Disease Receiving Conservative Care without Dialysis. AB - With the evidence that dialysis may not necessarily be beneficial for older adults with advanced chronic kidney disease (CKD), there is a growing interest in promoting conservative care without dialysis as a viable treatment option for these individuals. This review summarizes the current empirical evidence of symptom experiences and quality of life of patients receiving conservative care. Data suggest that conservative care may yield symptom experiences and quality of life that are compatible with those of patients on dialysis. However, these data are exclusively from studies conducted outside of the United States in which there were often no comparison groups or study designs that could provide high quality evidence. There is an urgent need for further research and developing a conservative care model suitable for CKD populations in the U.S. PMID- 26860541 TI - Water Quality Index for measuring drinking water quality in rural Bangladesh: a cross-sectional study. AB - BACKGROUND: Public health is at risk due to chemical contaminants in drinking water which may have immediate health consequences. Drinking water sources are susceptible to pollutants depending on geological conditions and agricultural, industrial, and other man-made activities. Ensuring the safety of drinking water is, therefore, a growing problem. To assess drinking water quality, we measured multiple chemical parameters in drinking water samples from across Bangladesh with the aim of improving public health interventions. METHODS: In this cross sectional study conducted in 24 randomly selected upazilas, arsenic was measured in drinking water in the field using an arsenic testing kit and a sub-sample was validated in the laboratory. Water samples were collected to test water pH in the laboratory as well as a sub-sample of collected drinking water was tested for water pH using a portable pH meter. For laboratory testing of other chemical parameters, iron, manganese, and salinity, drinking water samples were collected from 12 out of 24 upazilas. RESULTS: Drinking water at sample sites was slightly alkaline (pH 7.4 +/- 0.4) but within acceptable limits. Manganese concentrations varied from 0.1 to 5.5 mg/L with a median value of 0.2 mg/L. The median iron concentrations in water exceeded WHO standards (0.3 mg/L) at most of the sample sites and exceeded Bangladesh standards (1.0 mg/L) at a few sample sites. Salinity was relatively higher in coastal districts. After laboratory confirmation, arsenic concentrations were found higher in Shibchar (Madaripur) and Alfadanga (Faridpur) compared to other sample sites exceeding WHO standard (0.01 mg/L). Of the total sampling sites, 33 % had good-quality water for drinking based on the Water Quality Index (WQI). However, the majority of the households (67 %) used poor-quality drinking water. CONCLUSIONS: Higher values of iron, manganese, and arsenic reduced drinking water quality. Awareness raising on chemical contents in drinking water at household level is required to improve public health. PMID- 26860543 TI - Inner membrane proteins YgdD and SbmA are required for the complete susceptibility of E. coli to the proline-rich antimicrobial peptide arasin 1(1 25). AB - Arasin 1 from the spider crab Hyas araneus is a proline-rich antimicrobial peptide, which kills target bacteria by a non-membranolytic mechanism. By using a fluorescent derivative of the peptide, we showed that arasin 1 rapidly penetrates into Escherichia coli cells without membrane damage. To unravel its mode of action, a knock-out gene library of E. coli was screened and two types of mutants with a less susceptible phenotype to the arasin 1 fragment (1-23) were found. The first bore the mutation of sbmA, a gene coding for an inner membrane protein involved in the uptake of different antibiotic peptides. The second one was located in the ygdD gene, coding for a conserved inner membrane protein of unknown function. Functional studies showed that YgdD is required for the full susceptibility to arasin 1(1-25), possibly by supporting its uptake and/or intracellular action. These results indicate that different bacterial proteins are exploited by arasin 1(1-25) to exert its antibacterial activity and add new insights in the complex mode of action of proline-rich antimicrobial peptides. PMID- 26860545 TI - Rapid Repeat Pregnancy in Brazilian Adolescents: Interaction between Maternal Schooling and Age. AB - STUDY OBJECTIVE: An association between rapid repeat pregnancy (RRP; occurring within a birth interval of up to 24 months) and undesirable obstetric and perinatal outcomes has been shown, especially among adolescents and women without adequate schooling. The objective of this study was to evaluate the effect of the interaction between maternal schooling and age on the incidence of RRP. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A nonconcurrent cohort study was carried out using probabilistic record linkage techniques. The 59,400 linked records of singleton live-born infants delivered in 2002 whose mothers were up to 29 years old and lived in Rio de Janeiro City were evaluated. RESULTS: Compared with young adults with adequate schooling, the adjusted risk ratio for RRP for adolescents with inadequate schooling was 2.1 (95% confidence interval, 1.8-2.4). The attributable proportion was 0.16 (95% confidence interval, 0.02-0.29). CONCLUSION: Young maternal age and inadequate schooling interact, increasing RRP. PMID- 26860546 TI - Chronic retinoic acid treatment suppresses adult hippocampal neurogenesis, in close correlation with depressive-like behavior. AB - Clinical studies have highlighted an association between retinoid treatment and depressive symptoms. As we had shown before that chronic application of all-trans retinoic acid (RA) potently activated the hypothalamus-pituitary-adrenal (HPA) stress axis, we here questioned whether RA also induced changes in adult hippocampal neurogenesis, a form of structural plasticity sensitive to stress and implicated in aspects of depression and hippocampal function. RA was applied intracerebroventricularly (i.c.v.) to adult rats for 19 days after which animals were subjected to tests for depressive-like behavior (sucrose preference) and spatial learning and memory (water maze) performance. On day 27, adult hippocampal neurogenesis and astrogliosis was quantified using BrdU (newborn cell survival), PCNA (proliferation), doublecortin (DCX; neuronal differentiation), and GFAP (astrocytes) as markers. RA was found to increase retinoic acid receptor alpha (RAR-alpha) protein expression in the hippocampus, suggesting an activation of RA-induced signaling mechanisms. RA further potently suppressed cell proliferation, newborn cell survival as well as neurogenesis, but not astrogliosis. These structural plasticity changes were significantly correlated with scores for anhedonia, a core symptom of depression, but not with water maze performance. Our results suggest that RA-induced impairments in hippocampal neurogenesis correlate with depression-like symptoms but not with spatial learning and memory in this design. Thus, manipulations aimed to enhance neurogenesis may help ameliorate emotional aspects of RA-associated mood disorders. (c) 2016 Wiley Periodicals, Inc. PMID- 26860548 TI - Alteration of Polymeric Immunoglobulin Receptor and Neonatal Fc Receptor Expression in the Gut Mucosa of Immunodeficiency Virus-Infected Rhesus Macaques. AB - Polymeric immunoglobulin receptors (pIgR) and neonatal Fc receptors (FcRn) are crucial immunoglobulin (Ig) receptors for the transcytosis of immunoglobulins, that is IgA, IgM and IgG, the levels of which in mucosal secretions were altered in both HIV- and SIV-infected individuals. To gain an insight into the changes of pIgR and FcRn expression after immunodeficiency virus (SHIV/SIV) infection, real time RT-PCR methods were established and the mRNA levels of pIgR and FcRn in normal and SHIV/SIV-infected rhesus macaques were quantitatively examined. It was found that the levels of pIgR mRNA were within a range of 10(7) copies per million copies of GAPDH mRNA in the gut mucosa of rhesus macaques, which were up to 55 times higher than that in the oral mucosa, the highest among the non-gut tissues examined. Levels of FcRn mRNA were generally lower than that of pIgR, and the levels of FcRn mRNA in the gut mucosa were also lower than that in most non gut tissues examined. Notably, the levels of pIgR mRNA in the duodenal mucosa were positively correlated with that of IL-17A in normal rhesus macaques. Both pIgR and FcRn mRNA levels were significantly reduced in the duodenal mucosa during acute SHIV infection and in the jejunum and caecum during chronic SHIV/SIV infection. These data expanded our knowledge on the expression of pIgR and FcRn in the gastrointestinal tract of rhesus macaques and demonstrated altered expression of pIgR and FcRn in SHIV/SIV, and by extension HIV infections, which might have contributed to HIV/AIDS pathogenesis. PMID- 26860549 TI - Perceived barriers to and facilitators of being physically active during adjuvant cancer treatment. AB - OBJECTIVE: The aim was to describe cancer patients' perceived barriers and facilitators of physical activity during adjuvant cancer treatment. METHODS: Semi structured focus group interviews were conducted with patients with breast cancer (n=9) and colorectal cancer (n=1) and prostate cancer (n=8) undergoing adjuvant cancer treatment. To capture perceived barriers and facilitators before starting treatment, individual interviews with women with breast cancer (n=5) were also conducted. 23 patients in total, were interviewed, and the transcribed interviews were analysed with qualitative content analysis. RESULTS: Three categories emerged: "Physical and emotional barriers"-addresses experiences of side-effects, co-morbid conditions and emotional barriers, preventing physical activity (PA). "Perspective and attitudes"-how self-efficacy, self-image, preference, concerns, expectations, experience and new perspective regarding one's health influencing PA. "Support and practicalities"-addresses needs of support and information and how practicalities could be a barrier to PA. CONCLUSIONS: Several barriers were side effects of oncological treatment, which can be alleviated by PA. Another barrier was concerns regarding safety of PA during treatment. Communicating benefits and safety of PA to cancer patients early as possible after diagnosis might be beneficial. PRACTICE IMPLICATIONS: Information about PA from health care staff should be given early after diagnosis and as a part of standard care. PMID- 26860547 TI - Interhemispheric connections between the infralimbic and entorhinal cortices: The endopiriform nucleus has limbic connections that parallel the sensory and motor connections of the claustrum. AB - We have previously shown that the claustrum is part of an interhemispheric circuit that interconnects somesthetic-motor and visual-motor cortical regions. The role of the claustrum in processing limbic information, however, is poorly understood. Some evidence suggests that the dorsal endopiriform nucleus (DEn), which lies immediately ventral to the claustrum, has connections with limbic cortical areas and should be considered part of a claustrum-DEn complex. To determine whether DEn has similar patterns of cortical connections as the claustrum, we used anterograde and retrograde tracing techniques to elucidate the connectivity of DEn. Following injections of retrograde tracers into DEn, labeled neurons appeared bilaterally in the infralimbic (IL) cortex and ipsilaterally in the entorhinal and piriform cortices. Anterograde tracer injections in DEn revealed labeled terminals in the same cortical regions, but only in the ipsilateral hemisphere. These tracer injections also revealed extensive longitudinal projections throughout the rostrocaudal extent of the nucleus. Dual retrograde tracer injections into IL and lateral entorhinal cortex (LEnt) revealed intermingling of labeled neurons in ipsilateral DEn, including many double-labeled neurons. In other experiments, anterograde and retrograde tracers were separately injected into IL of each hemisphere of the same animal. This revealed an interhemispheric circuit in which IL projects bilaterally to DEn, with the densest terminal labeling appearing in the contralateral hemisphere around retrogradely labeled neurons that project to IL in that hemisphere. By showing that DEn and claustrum have parallel sets of connections, these results suggest that DEn and claustrum perform similar functions in processing limbic and sensorimotor information, respectively. J. Comp. Neurol. 525:1363-1380, 2017. (c) 2016 Wiley Periodicals, Inc. PMID- 26860550 TI - Risk factors for diabetic retinopathy in people with Type 2 diabetes: A case control study in a UK primary care setting. AB - AIM: To identify risk factors of diabetic retinopathy (DR) among people with Type 2 diabetes mellitus in UK primary care. METHODS: A case-control study nested in a cohort of incident Type 2 diabetes identified in The Health Improvement Network database from 2000 to 2007. Cases were people with DR (N=7735) and controls were a DR-free sample (N=9395). No age restrictions were applied. Adjusted odds ratios and 95% CIs were estimated. RESULTS: 21% of DR cases were identified during the first semester after Type 2 diabetes diagnosis. After controlling for delay on the Type 2 diabetes diagnosis, the DR risk increased with the duration of diabetes. DR increased with a mean systolic BP >=150mmHg (1.18; 1.10-1.27), high alcohol consumption (1.34; 1.11-1.61), glycated haemoglobin (>=75 to <86: 1.14; 1.00-1.31; >=86 to <97mmol/mol: 1.25; 1.07-1.45; >=97mmol/mol: 1.21; 1.07-1.37), microalbuminuria (1.16; 1.06-1.27), and retinal vein occlusion (2.47; 1.67-3.66). Glaucoma and retinal arterial occlusion showed an OR of 0.71 (0.60-0.84) and 0.63 (0.40-1.01), respectively. HDL >=1.55mmol/l (0.88; 0.80-0.98), high triglycerides (2.3-5.6mmol/l: 0.90; 0.82-0.99; >5.6mmol/l: 0.85; 0.64-1.13) or smoking (0.89; 0.81-0.97) had a slightly reduced DR risk. Users of hypoglycaemic agents had an increased DR risk. CONCLUSION: Some DR cases were identified near the diabetes diagnosis date suggesting that a delayed diabetes diagnosis is still common. Glaucoma, retinal arterial occlusion and high HDL levels were inversely associated with DR, while retinal vein occlusion, alcohol and other well-known risk factors were positively associated. PMID- 26860551 TI - Influence of scaffold morphology on co-cultures of human endothelial and adipose tissue-derived stem cells. AB - The interior of tissue engineering scaffolds must be vascularizable and allow adequate nutrients perfusion in order to ensure the viability of the cells colonizing them. The promotion of rapid vascularization of scaffolds is critical for thick artificial constructs. In the present study co-cultures of human endothelial and adipose tissue-derived stem cells have been performed in poly(ethyl acrylate) scaffolds with two different pore structures: grid-like (PEA o) or sponge-like (PEA-s), in combination with a self-assembling peptide gel filling the pores, which aims to mimic the physiological niche. After 2 and 7 culture days, cell adhesion, proliferation and migration, the expression of cell surface markers like CD31 and CD90 and the release of VEGF were assessed by means of immunocytochemistry, scanning electronic microscopy, flow cytometry and ELISA analyses. The study demonstrated that PEA-s scaffolds promoted greater cell organization into tubular-like structures than PEA-o scaffolds, and this was enhanced by the presence of the peptide gel. Paracrine signaling from adipose cells significantly improved endothelial cell viability, proving the advantageous combination of this system for obtaining easily vascularizable tissue engineered grafts. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1523 1533, 2016. PMID- 26860552 TI - Ultrahigh field NMR and MRI: Science at a crossroads. Report on a jointly-funded NSF, NIH and DOE workshop, held on November 12-13, 2015 in Bethesda, Maryland, USA. PMID- 26860553 TI - Quantitative Live Single-cell Mass Spectrometry with Spatial Evaluation by Three Dimensional Holographic and Tomographic Laser Microscopy. AB - The locations and volumes of the contents of a single HepG2 cell were visualized under three-dimensional (3D) holographic and tomographic (HT) laser microscopy, colored by refractive index, not staining. After trapping the specific area of a target cell in a nanospray tip, quantification was performed by live single-cell mass spectrometry. Comparison of the HepG2 cells' before and after 3D-HT images allowed the inference of the precise volume and original location of the trapped cell contents. The total amount of a trapped molecule was estimated. The images also revealed morphological changes in the cell structure caused by the manipulation. PMID- 26860554 TI - Color Change of Sudan III against Concentrated Sulfuric Acid in Acetonitrile and Quantification for a Small Amount of Concentrated Sulfuric Acid. AB - The color-changing phenomenon of hydrophobic bisazo dye, Sudan III in an acetonitrile solution against the addition of concentrated sulfuric acid has been discovered and the chromic properties investigated. Based on observations, a novel quantification method of concentrated sulfuric acid has been developed. Sudan III changes its color from orange to blue against a small volume of sulfuric acid, and the acetonitrile solution of Sudan III is the most suitable for observing the color-change phenomenon. (1)H-NMR and UV-Vis spectroscopic studies showed that the color-change mechanism of Sudan III against sulfuric acid is due to the protonation of the dye by sulfuric acid. This phenomenon is applicable to the quantification of concentrated sulfuric acid by introducing the Hammett acidity function. The proposed method requires only a small amount of the sample, 0.04 mL, and enables rapid quantification. PMID- 26860555 TI - Low-interferences Determination of the Antioxidant Capacity in Fruits Juices Based on Xanthine Oxidase and Mediated Amperometric Measurements in the Reduction Mode. AB - A low-interferences enzymatic sensor for evaluating the antioxidant capacity was developed. Xanthine oxidase was used to produce superoxide radicals that spontaneously dismutate to hydrogen peroxide. Low xanthine concentrations were used to minimize the rapid dismutation of the superoxide radical before its fast reaction with antioxidants. The sensor operates in the reduction mode, and evaluations with low interferences of the antioxidant capacity are based on the detection of remaining hydrogen peroxide using Prussian blue electrodes at low potentials. The linear calibration graph is between 2 - 10 MUM ascorbic acid. No interferences were observed from easily oxidisable substances including uric acid, which is produced in the enzymatic reaction or other substances usually found in foods. The method was used to evaluate the antioxidant capacity in different real juice samples. PMID- 26860556 TI - Improved Gas Chromatographic Determination of Guanidino Compounds Using Isovaleroylacetone and Ethyl Chloroformate as Derivatizing Reagents. AB - An improved GC method in terms of sensitivity and decrease in the analysis time has been developed for the analysis of eight guanidino compounds: guanidine (G), methylguanidine (MG), creatinine (CTN), guanidinoacetic acid (GAA), guanidinobutyric acid (GBA), guanidinopropionic acid (GPA), argenine (Arg), and guanidinosuccinic acid (GSA), using isovaleroylacetone (IVA) and ethyl chloroformate (ECF) as derivatizing reagents. The separation was obtained from column HP-5 (30 m * 0.32 mm i.d.) with film thickness of 0.25 MUm within 11 min. The linear calibrations were obtained with 0.5 to 50 MUg/mL with coefficient of determination (R(2)) within 0.9969 - 0.9998. Limits of detections (LODs) were within 5 - 140 ng/mL. The derivatization, separation and determination was repeatable (n = 6) with relative standard deviation (RSD) within 1.2 - 3.1%. The guanidino compounds were determined in deproteinized serum of healthy volunteers and uremic patients within below LOD to 8.8 MUg/mL and below LOD to 43.99 MUg/mL with RSD within 1.4 - 3.6%. The recovery of guanidino compounds calculated by standard addition from serum was within 96.1 - 98.9%, with RSD 1.4 - 3.6%. PMID- 26860557 TI - Analysis of Disperse Dyes Using Liquid Chromatography/Linear Ion Trap Mass Spectrometry (LC/LIT-MSn) and Database Construction. AB - Liquid chromatography/linear ion trap mass spectrometry (LC/LIT-MS(n)) was used to construct a database of disperse dyes. Fifty-three standard dyes were subjected to LC/LIT-MS(n) and characterized based on their mass spectra (MS, MS(2), and MS(3)), values of lambdamax (maximum absorption wavelength in the UV visible spectrum), and retention times. The results demonstrate that it is possible to reliably identify coexisting dyes that cannot be separated by LC or detected by diode array detection due to their low molecular absorption coefficients. In addition, the by-products included in the standard dyes were found to provide important information for the identification and discrimination of dyestuffs synthesized using different processes. The confirmation of the effectiveness of LC/LIT-MS(n) analysis in detecting small amounts of disperse dyes in this study shows its potential for use in the discrimination of dyed fibers obtained at crime scenes. PMID- 26860558 TI - Development of a High-Sensitivity Quantitation Method for Arginine Vasopressin by High-Performance Liquid Chromatography Tandem Mass Spectrometry, and Comparison with Quantitative Values by Radioimmunoassay. AB - Human plasma arginine vasopressin (AVP) levels serve as a clinically relevant marker of diabetes and related syndromes. We developed a highly sensitive method for measuring human plasma AVP using high-performance liquid chromatography tandem mass spectrometry. AVP was extracted from human plasma using a weak-cation solid-phase extraction plate, and separated on a wide-bore octadecyl reverse phase column. AVP was quantified in ion-transition experiments utilizing a product ion (m/z 328.3) derived from its parent ion (m/z 542.8). The sensitivity was enhanced using 0.02% dichloromethane as a mobile-phase additive. The lower limit of quantitation was 0.200 pmol/L. The extraction recovery ranged from 70.2 +/- 7.2 to 73.3 +/- 6.2% (mean +/- SD), and the matrix effect ranged from 1.1 - 1.9%. Quality-testing samples revealed interday/intraday accuracy and precision ranging over 0.9 - 3% and -0.3 - 2%, respectively, which included the endogenous baseline. Our results correlated well with radioimmunoassay results using 22 human volunteer plasma samples. PMID- 26860559 TI - Efficient Detection of Trace Hg2+ in Water Based on the Fluorescence Quenching of Environment-friendly Thiol-functionalized Poly(vinyl alcohol) Capped CdS Quantum Dots Nanocomposite. AB - Using environment-friendly materials for sensing toxic metal ions has drawn significant attention in recent research. Herein, we present an aqueous synthesis of stable CdS quantum dots (QDs) using thiol-functionalized poly(vinyl alcohol) (PVA) as the unique capping ligand for the detection of trace Hg(2+) in environmental water samples. The CdS QDs with an average size of 3.3 nm had good water-solubility and favorable fluorescence with a quantum yield of 32.8% and a longer luminescence lifetime of 31.9 ns. The fluorescence intensity of QDs aqueous solution in the 520 nm wavelength was quenched upon the addition of Hg(2+). Under the optimal conditions, the ratio of the blank fluorescence intensity to the quenched fluorescence intensity was linearly proportional to the Hg(2+) concentration from 2 to 4000 nM with a detection limit of 1 nM. Also, many co-existing metal ions were not interfered with the detection of Hg(2+). This nanomaterial was successfully applied to the measurement of Hg(2+) in water samples. PMID- 26860560 TI - Simultaneous Quantification of Iodine and Other Elements in Infant Formula by ICP MS Following an Acid Digestion with Nitric Acid and Hydrogen Peroxide. AB - A method for quantifying iodine in infant formula is described. Nitric acid and hydrogen peroxide converted iodine into iodate in microwave-assisted digestion and prevented iodine volatilization and memory effects. Acetic acid as a carbon source was added to both the sample and standard solutions as a countermeasure against carbon charge transfer to iodine and the addition of acetic acid helped to enhance the sensitivity. The instrument limit of quantification was 0.1 ng mL( 1) and the relative standard deviation was less than 3%. The spike recoveries were between 94.8 and 106%. Good agreement with the values obtained using the tetramethylammonium hydroxide method was obtained for infant formula sold in several countries. This method permitted the simultaneous determination of iodine and 12 other important elements (Na, Mg, P, K, Ca, Cr, Mn, Fe, Cu, Zn, Se and Mo) in infant formula. PMID- 26860562 TI - Pulsed Discharge Helium Ionization Detector for Highly Sensitive Aquametry. AB - Trace moisture quantitation is crucial in medical, civilian and military applications. Current aquametry technologies are limited by the sample volume, reactivity, or interferences, and/or instrument size, weight, power, cost, and complexity. We report for the first time on the use of a pulsed discharge helium ionization detector (PDHID-D2) (~196 cm(3)) for the sensitive (limit of detection, 0.047 ng; 26 ppm), linear (r(2) >0.99), and rapid (< 2 min) quantitation of water using a small (0.2 - 5.0 MUL) volume of liquid or gas. The relative humidity sensitivity was 0.22% (61.4 ppmv) with a limit of detection of less than 1 ng moisture with gaseous samples. The sensitivity was 10 to 100 to fold superior to competing technologies without the disadvantages inherent to these technologies. The PDHID-D2, due to its small footprint and low power requirement, has good size, weight, and power-portability (SWAPP) factors. The relatively low cost (~$5000) and commercial availability of the PDHID-D2 makes our technique applicable to highly sensitive aquametry. PMID- 26860561 TI - Improvement and Interlaboratory Validation of the Lipophilic Oxygen Radical Absorbance Capacity: Determination of Antioxidant Capacities of Lipophilic Antioxidant Solutions and Food Extracts. AB - A lipophilic oxygen radical absorbance capacity (L-ORAC) assay is an evaluation of the antioxidant capacity of solutions of lipophilic compounds. The concentrations of fluorescein, radical generator, and Trolox standard solutions were optimized to improve the precision of the assay. An interlaboratory study using two antioxidant solutions and three food extracts as test samples conducted in accordance with harmonized protocol demonstrated satisfactory L-ORAC measurements; the intermediate precision relative standard deviations (RSD(int)) ranged from 7.0 to 16.7%, the reproducibility relative standard deviations (RSD(R)) ranged from 14.8 to 19.4%, and the HorRat values ranged from 1.35 to 1.78. PMID- 26860563 TI - An Improved Pneumatic Nebulization Gas-Solid Microextraction Device Used to Detect Triazine Herbicides in White Spirit. AB - The pneumatic nebulization gas-solid microextraction device fascinating us is because it directly atomized organic samples to cross a solid-phase microextraction (SPME) cartridge without any pretreatment. In this work, both the spray chamber and SPME column of the extraction device were heated. We found that this would significantly improve the extraction efficiency of this method. Then, this method was used to detect seven triazine herbicides (atraton, desmetryn, atrazine, terbumeton, terbuthylazine, terbutryn, and dipropetryn) in drinking alcohol samples. The experimental results indicated that this extraction procedure could conveniently, efficiently and accurately concentrate any triazine herbicides from drinking alcohol samples. The limits of detection (LODs) were from 0.08 to 0.23 MUg L(-1), the limits of quantification (LOQs) were from 0.27 to 0.78 MUg L(-1). We used this method to detect triazine herbicides in five white spirit samples. Four concentrations were chosen (5, 25, 50 and 100 MUg L( 1)) as the amounts of spikes to investigate the recovery and precision of the present PN-GSME method. The recoveries ranged from 95.91 to 106.67%. The relative standard deviations were not more than 6.51%. Also this method matches the requirement of the maximum residue limits of the European Union. PMID- 26860564 TI - Analysis of Ion Transport through a Single Channel of Gramicidin A in Bilayer Lipid Membranes. AB - Ion transport through a single channel of gramicidin A (GA) within the bilayer lipid membrane (BLM) between two aqueous phases (W1 and W2) has been analyzed based on the electroneutrality principle. The single-channel current increases in proportion to the magnitude of the applied membrane potential and is also dependent on the permeability coefficients of electrolyte ions (K(+) and Cl(-)). By varying the ratio of the concentration of KCl in W1 to that in W2, the ratio of the diffusion coefficient of K(+) in the BLM to that of Cl(-) in the BLM can be evaluated. PMID- 26860565 TI - Selective Determination of Trinitrotoluene Based on Energy Transfer between Carbon Dots and Gold Nanoparticles. AB - A fluorescence resonance energy transfer (FRET) system between carbon dots (C dots) and amine-capped gold nanoparticles (AuNPs) was developed for the selective determination of 2,4,6-trinitrotoluene (TNT). C-dots have an intrinsic florescence emission depending on their exciting wavelength. In the presence of AuNPs, C-dots adsorb on the Au surfaces, and NPs treat as energy acceptor, which can receive light emitted by C-dots, leading to decrease the fluorescence intensity of C-dots. Furthermore, it is observed that nitroaromatic compounds, especially TNT, could restore this fluorescence due to selective interaction with AuNPs via amine groups, and so releasing the C-dots. Based on this effect, a sensitive and selective fluorescence turn-on probe was designed for the determination of TNT. Some important factors including AuNPs and C-dot concentrations and media pH, which would affect the efficiency of the probe, were optimized. Under the optimum experimental conditions, good linear relationships in the range of 7 - 250 nmol L(-1) TNT with the detection limit of 2.2 nmol L(-1) were obtained. The proposed method was satisfactorily applied to the determination of TNT in the environmental water samples. Compared with previous reports, the developed method has relatively high sensitivity, short analysis time, low cost and ease of operation. PMID- 26860567 TI - Forensic Identification of Automobile Window Glass Manufacturers in Japan Based on the Refractive Index, X-ray Fluorescence, and X-ray Absorption Fine Structure. AB - In this study, 3 automobile window glass manufacturers were identified based on refractive index, XRF, and XAFS analyses. The samples were classified into the corresponding groups using XRF, which should be the first step for identification. Samples having different manufacturing times showed differences in the refractive index. Based on XAFS, the amplitude of the EXAFS spectra and the intensities of Fourier transforms differed between manufacturers. In the scheme for manufacturer identification proposed in this study, performing XRF and refractive index studies is the first step. The concentrations of CeO2, MgO, Al2O3, and K2O allowed us to distinguish among manufacturers. Secondly, for samples containing cerium, we discriminated between manufacturer based on the amplitude of the EXAFS spectra and the intensities of Fourier transforms. As a result, the manufacturers of the 75 samples used in this study were multilaterally identified. PMID- 26860566 TI - Structure-matched Phthalocyanine Ion Pair as a Red-emitting Fluorescent Optical Probe for the Analysis of Sodium Dodecylbenzenesulfonate with High Specificity and Sensitivity. AB - We have found that a positively charged cationic copper phthalocyanine, Alcian blue (Alcian blue 8GX), can efficiently quench the fluorescence of an oppositely charged red fluorescent phthalocyanine compound with a matched molecular structure, tetrasulfonated aluminum phthalocyanine (AlS4Pc), because of the formation of an ion pair complex (AlS4Pc-Alcian blue 8GX) that exhibits almost no fluorescence. An investigation was carried out on the fluorescence recovery of AlS4Pc-Alcian blue 8GX caused by a series of anionic surfactants containing a sulfonic group (sodium dodecylbenzenesulfonate (SDBS), sodium lauryl sulfate (SLS), and sodium dodecyl sulfate (SDS)). The results showed that SDBS exhibited a significant response, and the highest sensitivity among the surfactants. Due to its high efficiency of fluorescence quenching and the high level of fluorescence recovery, direct observes can even be performed by the naked eye. The results revealed that the Alcian blue 8GX-AlS4Pc ion-pair complex fluorescent probe only responded to SDBS in the low-concentration range. Based on the new founding, this study proposed a novel principle and method of fluorescence enhancement to specifically measure the concentration of SDBS, thereby achieving a highly sensitive and highly specific determination of SDBS. Under the optimal conditions, the fluorescence intensity (I(f)) of the system and the concentration of SDBS in the range of 1 * 10(-7) - 1 * 10(-5) mol/dm(3) exhibited a good linear relationship. This method is highly sensitive, and the operation is simple and rapid. It had been applied for the quantitative analysis of SDBS in environmental water, while achieving satisfactory results compared with those of the standard method. This study developed a new application of the fluorescent phthalocyanine compounds used as molecular probes in analytical sciences. PMID- 26860568 TI - Establishment and Application of a Visual DNA Microarray for the Detection of Food-borne Pathogens. AB - The accurate detection and identification of food-borne pathogenic microorganisms is critical for food safety nowadays. In the present work, a visual DNA microarray was established and applied to detect pathogens commonly found in food, including Salmonella enterica, Shigella flexneri, E. coli O157:H7 and Listeria monocytogenes in food samples. Multiplex PCR (mPCR) was employed to simultaneously amplify specific gene fragments, fimY for Salmonella, ipaH for Shigella, iap for L. monocytogenes and ECs2841 for E. coli O157:H7, respectively. Biotinylated PCR amplicons annealed to the microarray probes were then reacted with a streptavidin-alkaline phosphatase conjugate and nitro blue tetrazolium/5 bromo-4-chloro-3'-indolylphosphate, p-toluidine salt (NBT/BCIP); the positive results were easily visualized as blue dots formatted on the microarray surface. The performance of a DNA microarray was tested against 14 representative collection strains and mock-contamination food samples. The combination of mPCR and a visual micro-plate chip specifically and sensitively detected Salmonella enterica, Shigella flexneri, E. coli O157:H7 and Listeria monocytogenes in standard strains and food matrices with a sensitivity of ~10(2) CFU/mL of bacterial culture. Thus, the developed method is advantageous because of its high throughput, cost-effectiveness and ease of use. PMID- 26860569 TI - Spectroscopic Characteristic and Analytical Capability of Ar-N2 Inductively Coupled Plasma in Axially Viewing Optical Emission Spectrometry. AB - The spectroscopic characteristics and analytical capability of argon-nitrogen (Ar N2) inductively coupled plasma (ICP) in axially viewing optical emission spectrometry (OES) were examined and figures of merit were determined in the present study. The spectroscopic characteristics such as the emission intensity profile and the excitation temperature observed from the analytical zone of Ar-N2 ICP in axially viewing ICPOES, in order to elucidate the enhancement of the emission intensity of elements obtained in our previous study, were evaluated and compared to those of the standard ICP. The background and emission intensities of elements as well as their excitation behavior for both atom and ion lines were also examined. As results, a narrower emission intensity profile and an increased excitation temperature as well as enhancements for both background and emission intensities of elements, which could be due to the ICP shrunken as well as the enhancement of the interaction between the central channel of the ICP and samples introduced, were observed for Ar-N2 ICP in axially viewing OES. In addition, the elements with relatively higher excitation and ionization energies such as As, Bi, Cd, Ni, P, and Zn revealed larger enhancements of the emission intensities as well as improved limits of detection (LODs), which were also attributed to the enhanced interaction between Ar-N2 ICP and the samples. Since the Ar-N2 ICP could be obtained easily only by the addition of a small amount of N2 gas to the Ar plasma gas of the standard ICP and no optimization on the alignment between Ar-N2 ICP and the spectrometer in commercially available ICPOES instruments was needed, it could be utilized as simple and optional excitation and ionization sources in axially viewing ICPOES. PMID- 26860570 TI - Diagnosis of Periodontal Disease from Saliva Samples Using Fourier Transform Infrared Microscopy Coupled with Partial Least Squares Discriminant Analysis. AB - Diagnosis of periodontal disease by Fourier transform infrared (FT-IR) microscopic technique was achieved for saliva samples. Twenty-two saliva samples, collected from 10 patients with periodontal disease and 12 normal volunteers, were pre-processed and analyzed by FT-IR microscopy. We found that the periodontal samples showed a larger raw IR spectrum than the control samples. In addition, the shape of the second derivative spectrum was clearly different between the periodontal and control samples. Furthermore, the amount of saliva content and the mixture ratio were different between the two samples. Partial least squares discriminant analysis was used for the discrimination of periodontal samples based on the second derivative spectrum. The leave-one-out cross-validation discrimination accuracy was 94.3%. Thus, these results show that periodontal disease may be diagnosed by analyzing saliva samples with FT-IR microscopy. PMID- 26860571 TI - Benzo[c]fluorene in Urban Air: HPLC Determination and Mutagenic Contribution Relative to Benzo[a]pyrene. AB - Benzo[c]fluorene (BcFE) concentrations in benzene/ethanol extracts of airborne particulates were determined by high-performance liquid chromatography (HPLC) with fluorescence detection. HPLC conditions were as follows: columns, two ZORBAX Eclipse PAH (4.6 i.d. * 250 mm, 3.5 MUm) and one Inertsil ODS-P (4.6 i.d. * 250 mm, 5 MUm) in series; mobile phase, acetonitrile-water (98:2, v/v), 0.3 mL/min; detection wavelengths, excitation 309 nm, emission 354 nm. Particulate-phase BcFE concentrations in the atmosphere varied seasonally (winter > summer). The concentrations were 11000 +/- 6100 pg m(-3) (winter) and 40 +/- 12 pg m(-3) (summer) in Beijing, China, and 13 +/- 5.0 pg m(-3) (winter) and 2.7 +/- 0.52 pg m(-3) (summer), in Kanazawa, Japan. In both cities, the particulate-phase BcFE concentration in the atmosphere was lower than that of benzo[a]pyrene (BaP) by a factor of 0.03 - 0.43. However, the mutagenic contribution of particulate-phase BcFE in the atmosphere in winter calculated from the mutagenicity relative potency factor was greater than that of BaP. PMID- 26860572 TI - The Use of an Enzyme-based Sensor Array to Fingerprint Proteomic Signatures of Sera from Different Mammalian Species. AB - A cross-reactive sensor array consisting of polyion complexes (PICs) between anionic enzymes and poly(ethylene glycol)-modified (PEGylated) polyamines has been used to identify the source of mammalian sera. Although the catalytic activity of enzymes was inhibited by PIC formation with PEGylated polyamines, the subsequent addition of sera caused enzyme releases from PICs through competitive interactions between PICs and serum proteins, generating unique response patterns of changes in the enzyme activity. Linear discriminant analysis of the obtained patterns enabled the discrimination of five sera from different mammalian sources. PMID- 26860573 TI - Visual Assay of Total Iron in Human Serum with Bathophenanthrolin Disulfonate accommodated MCM-41. AB - A simple visual method for determining the total iron in human serum is proposed based on color development in the nanospace of mesoporous silica MCM-41 and a chromogenic ligand bathophenathroline disulfonate (BPS). Observing the color intensity of a complex between iron(II) and BPS devloped on the MCM-41 material by the naked eye enabled us to quntify iron(II) with a detection limit of 0.5 MUM. The BPS-loaded MCM-41 was successfully applied for quantifying the total iron in human serum. PMID- 26860574 TI - A Flow Method for Chemiluminescence Determination of Antimony(III) and Antimony(V) Using a Rhodamine B-Cetyltrimethylammonium Chloride Reversed Micelle System Following On-Line Extraction. AB - A rapid and sensitive flow method, based on the combination of on-line solvent extraction with reversed micellar mediated chemiluminescence (CL) detection using rhodamine B (RB), was developed for the determination of antimony(III) and antimony(V) in aqueous samples. The on-line extraction procedure involved ion pair formation of the antimony(V) chloro-complex anion with the protonated RBH(+) ion and its extraction from an aqueous hydrochloric acid solution into toluene, followed by phase separation using a microporous membrane. When in a flow cell of a detector, the ion-pair in the extract driven was mixed with the reversed micellar solution of cetyltrimethylammonium chloride in 1-hexanol cyclohexane/water (0.60 mol dm(-3) H2SO4) containing cerium(IV), its uptake by the reversed micelles and the subsequent CL oxidation of RB with Ce(IV) occurred easily, then the produced CL signal was measured. Using the proposed flow method under the optimized experimental conditions, a detection limit (DL) of 0.35 MUmol dm(-3) and a linear calibration graph with a dynamic range from DL to 16 MUmol dm(-3) were obtained for Sb(V) with a precision of 1.4% relative standard deviation (n = 5) at the Sb(V) concentration of 8.2 MUmol dm(-3). The present method was successfully applied to the determination of Sb(V) in water samples and to the differential determination of Sb(III) and Sb(V) in copper electrolyte industrial samples, where total antimony Sb(III) + Sb(V) was determined after oxidation of Sb(III) to Sb(V) with Ce(IV) and Sb(III) was calculated by difference, for which the DL was almost the same as that for Sb(V). PMID- 26860575 TI - Photophysical Properties of the 2-Hydroxytryptanthrin and Its Sodium Salt as Near infrared Dyes for Fluorescent Imaging. AB - 2-Hydroxytryptanthrin (T2OH) and its sodium salt (sodium tryptanthrin-2-olate, T2ONa) were synthesized as near-infrared (NIR) dyes for fluorescent imaging. The absorption maxima (lambda(a,max)) of T2OH under a pH range from 1.3 to 7.2 and from 8.5 to 10.6 were ca. 410 nm and ca. 495 nm, respectively. Moreover, the fluorescence maxima (lambda(f,max)) were ca. 660 nm regardless of the pH range. T2ONa was water soluble and the lambdaf,max were ca. 660 nm in both aprotic and protic solvents. PMID- 26860576 TI - Multiphoton Ionization Time-of-Flight Mass Spectrometry for the Detection of Bioactive Lignan. AB - Multiphoton ionization time-of-flight mass spectrometry (MPI-TOFMS) combined with a pulsed laser for sample vaporization was developed for the detection of a low volatile compound in a solution. A solution containing Taiwanin A ((3E,4E)-3,4 bis(1,3-benzodioxol-5-ylmethylene)dihydro-2(3H)-furanone), which is a lignan that has an anticancer effect, was employed in the present study. Consequently, Taiwanin A could be detected by irradiating a laser pulse for vaporization to an inlet nozzle, rather than by heating. Therefore, the present method could be effective for detecting compounds with lower volatilities in a liquid sample. PMID- 26860578 TI - Injection anaesthesia with fentanyl-midazolam-medetomidine in adult female mice: importance of antagonization and perioperative care. AB - Injection anaesthesia is commonly used in laboratory mice; however, a disadvantage is that post-anaesthesia recovery phases are long. Here, we investigated the potential for shortening the recovery phase after injection anaesthesia with fentanyl-midazolam-medetomidine by antagonization with naloxone flumazenil-atipamezole. In order to monitor side-effects, the depth of anaesthesia, heart rate (HR), core body temperature (BT) and concentration of blood gases, as well as reflex responses, were assessed during a 50 min anaesthesia. Mice were allowed to recover from the anaesthesia in their home cages either with or without antagonization, while HR, core BT and spontaneous home cage behaviours were recorded for 24 h. Mice lost righting reflex at 330 +/- 47 s after intraperitoneal injection of fentanyl-midazolam-medetomidine. During anaesthesia, HR averaged 225 +/- 23 beats/min, respiratory rate and core BT reached steady state at 131 +/- 15 breaths/min and 34.3 +/- 0.25C, respectively. Positive pedal withdrawal reflex, movement triggered by tail pinch and by toe pinch, still occurred in 25%, 31.2% and 100% of animals, respectively. Arterial blood gas analysis revealed acidosis, hypoxia, hypercapnia and a marked increase in glucose concentration. After anaesthesia reversal by injection with naloxone flumazenil-atipamezole, animals regained consciousness after 110 +/- 18 s and swiftly returned to physiological baseline values, yet they displayed diminished levels of locomotion and disrupted circadian rhythm. Without antagonization, mice showed marked hypothermia (22 +/- 1.9C) and bradycardia (119 +/- 69 beats/min) for several hours. Fentanyl-midazolam-medetomidine provided reliable anaesthesia in mice with reasonable intra-anaesthetic side-effects. Post-anaesthetic period and related adverse effects were both reduced substantially by antagonization with naloxone-flumazenil-atipamezole. PMID- 26860579 TI - Post-exposure prophylaxis against rabies is still needed after a bite from a vaccinated animal. PMID- 26860580 TI - Normal-Weight Central Obesity and Mortality Risk in Older Adults With Coronary Artery Disease. AB - OBJECTIVE: To study the relationship between body mass index (BMI) and central obesity and mortality in elderly patients with coronary artery disease (CAD). PATIENTS AND METHODS: We identified 7057 patients 65 years or older from 5 cohort studies assessing mortality risk using either waist circumference (WC) or waist hip ratio (WHR) in patients with CAD from January 1, 1980, to December 31, 2008. Normal weight, overweight, and obesity were defined using standard BMI cutoffs. High WHR was defined as 0.85 or more for women and 0.90 or more for men. High WC was defined as 88 cm or more for women and 102 cm or more for men. Separate models examined WC or WHR in combination with BMI (6 categories each) as the primary predictor (referent = normal BMI and normal WC or WHR). Cox proportional hazards models investigated the relationship between these obesity categories and mortality. RESULTS: Patients' mean age was 73.0+/-6.0 years (3741 [53%] women). The median censor time was 7.1 years. A normal BMI with central obesity (high WHR or high WC) demonstrated highest mortality risk (hazard ratio [HR], 1.29; 95% CI, 1.14-1.46; HR, 1.29; 95% CI, 1.12-1.50, respectively). High WHR was also predictive of mortality in the overall (HR, 2.14; 95% CI, 1.93-2.38) as well as in the sex-specific cohort. In the overall cohort, high WC was not predictive of mortality (HR, 1.04; 95% CI, 0.97-1.12); however, it predicted higher risk in men (HR, 1.12; 95% CI, 1.01-1.24). CONCLUSION: In older adults with CAD, normal weight central obesity defined using either WHR or WC is associated with high mortality risk, highlighting a need to combine measures in adiposity-related risk assessment. PMID- 26860581 TI - Synthesis, Characterization & Screening for Anti-Inflammatory & Analgesic Activity of Quinoline Derivatives Bearing Azetidinones Scaffolds. AB - BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDS) are clinically used as anti-inflammatory, analgesic and antipyretic agents but they have the drawbacks such as gastric irritation and gastric ulceration. Recently, quinoline derivatives have shown significant anti-inflammatory and less ulcerogenic activity. The present study deals with the synthesis and pharmacological assessment of a series of novel quinoline derivatives bearing azetidinones scaffolds as anti-inflammatory and analgesic agents. METHODS: A series of newer 3 chloro-1-(substituted)-4-(tetrazolo [1,5-a]quinolin-4- yl)azetidin-2-one derivatives (6a-l) was synthesized starting with acetanilide (1). Initially, acetanilide (1) was allowed to react with Vilsmeier-Haack reagent (DMF + POCl3) to form 2- chloro-3-formyl quinoline (2). The 2-chloro-3-formyl quinoline (2) was further treated with p-toluenesulphonic acid and sodium azide which yielded Tetrazolo [1,5-1] quinoline-4- carbaldehyde (3). The reaction of formyl group with various substituted amines (4a-l) formed corresponding Schiff base intermediates (5a-l), which were further allowed to react with chloroacetyl chloride to produce 3-chloro-1-(substituted)-4-(tetrazolo [1,5-a]quinolin-4-yl) azetidin-2-one derivatives (6a-l). The structure of the final analogues (6a-l) has been confirmed on the basis of elemental analysis, IR, 1H NMR, 13C NMR and mass spectra. All the synthesized compounds were evaluated for their anti inflammatory and analgesic activities by using carrageenan induced rat paw model and Eddy's hot plate method respectively. RESULTS: All the values of elemental analysis, IR, 1H NMR, 13C NMR and mass spectra were found to be prominent. The anti-inflammatory activity test revealed that 3-chloro-1-(4-methoxyphenyl)- 4 (tetrazolo[1,5-a] quinolin-4-yl)azetidin-2-one (6b), 3-chloro-1-(2-methoxyphenyl) 4-(tetrazolo[1,5-a]quinolin-4-yl)azetidin-2-one (6a) exhibited significant anti inflammatory and analgesic activity as compared to control group. CONCLUSION: The results of the current study indicate that substitution at quinoline derivatives bearing azetidinones scaffolds showed potent analgesic and anti-inflammatory activities. PMID- 26860582 TI - Experimental demonstration on the deterministic quantum key distribution based on entangled photons. AB - As an important resource, entanglement light source has been used in developing quantum information technologies, such as quantum key distribution(QKD). There are few experiments implementing entanglement-based deterministic QKD protocols since the security of existing protocols may be compromised in lossy channels. In this work, we report on a loss-tolerant deterministic QKD experiment which follows a modified "Ping-Pong"(PP) protocol. The experiment results demonstrate for the first time that a secure deterministic QKD session can be fulfilled in a channel with an optical loss of 9 dB, based on a telecom-band entangled photon source. This exhibits a conceivable prospect of ultilizing entanglement light source in real-life fiber-based quantum communications. PMID- 26860583 TI - Mapping the Interaction Network of Key Proteins Involved in Histone mRNA Generation: A Hydrogen/Deuterium Exchange Study. AB - Histone pre-mRNAs are cleaved at the 3' end by a complex that contains U7 snRNP, the FLICE-associated huge protein (FLASH) and histone pre-mRNA cleavage complex (HCC) consisting of several polyadenylation factors. Within the complex, the N terminus of FLASH interacts with the N terminus of the U7 snRNP protein Lsm11, and together they recruit the HCC. FLASH through its distant C terminus independently interacts with the C-terminal SANT/Myb-like domain of nuclear protein, ataxia-telangiectasia locus (NPAT), a transcriptional co-activator required for expression of histone genes in S phase. To gain structural information on these interactions, we used mass spectrometry to monitor hydrogen/deuterium exchange in various regions of FLASH, Lsm11 and NPAT alone or in the presence of their respective binding partners. Our results indicate that the FLASH-interacting domain in Lsm11 is highly dynamic, while the more downstream region required for recruiting the HCC exchanges deuterium slowly and likely folds into a stable structure. In FLASH, a stable structure is adopted by the domain that interacts with Lsm11 and this domain is further stabilized by binding Lsm11. Notably, both hydrogen/deuterium exchange experiments and in vitro binding assays demonstrate that Lsm11, in addition to interacting with the N terminal region of FLASH, also contacts the C-terminal SANT/Myb-like domain of FLASH, the same region that binds NPAT. However, while NPAT stabilizes this domain, Lsm11 causes its partial relaxation. These competing reactions may play a role in regulating histone gene expression in vivo. PMID- 26860584 TI - Towards universal quantum computation through relativistic motion. AB - We show how to use relativistic motion to generate continuous variable Gaussian cluster states within cavity modes. Our results can be demonstrated experimentally using superconducting circuits where tuneable boundary conditions correspond to mirrors moving with velocities close to the speed of light. In particular, we propose the generation of a quadripartite square cluster state as a first example that can be readily implemented in the laboratory. Since cluster states are universal resources for universal one-way quantum computation, our results pave the way for relativistic quantum computation schemes. PMID- 26860586 TI - Cost Differential of Chemotherapy for Solid Tumors. AB - PURPOSE: A significant portion of national cancer expenditure is attributed to chemotherapy.Although the National Comprehensive Cancer Network has generated recommendations for the treatment of various solid tumors, the outlined chemotherapeutic strategies lack information about the cost differential for increasing effectiveness. METHODS: Chemotherapy regimens (curative [adjuvant/neoadjuvant] and metastatic therapy) and dosages outlined in the 2013 National Comprehensive Cancer Network guidelines were acquired for four common cancers: bladder, breast, colon, and lung. Baseline drug and treatment costs (in US dollars)were calculated for the average US adult male on the basis of the payment allowance in the 2013 Medicare Part B average sales price (ASP) drug pricing files. Costs were extrapolated for a treatment period of 6 months. RESULTS: Of the 62 regimens included, the 6-month mean cost of chemotherapy was $26,989 +/- $29,971, and the median cost was $9,611 (interquartile range, $6,305 $39,383). The mean cost of metastatic cancer therapy regimens (n = 32) was $35,315 +/- 32,962 compared with $18,107 +/- 23,873 for curative therapy (P = .02). Of the 13 regimens with biologics used, the mean costs were $77,278 versus $13,646 for 49 regimens that did not use biologics (P<.001). The cost differential between extremes of costs for regimens with presumed similar efficacy was $90,843 ($79,165 for curative therapy and $90,210 for metastatic cancer therapy). The highest cost differential was noted in breast cancer regimens at $71,041 for metastatic cancer therapy and $63,926 for curative therapy. CONCLUSION: A significant cost differential exists between chemotherapeutic regimens for the most common solid tumors. Incorporation of costs and incremental effectiveness in current guidelines may encourage socially responsible practice patterns. PMID- 26860585 TI - Long-term clinical outcomes of everolimus-eluting stent versus paclitaxel-eluting stent in patients undergoing percutaneous coronary interventions: a meta analysis. AB - BACKGROUND: Everolimus -eluting stent (EES) is common used in patients undergoing percutaneous coronary interventions (PCI). Our purpose is to evaluate long-term clinical outcomes of everolimus -eluting stent (EES) versus paclitaxel-eluting stent (PES) in patients undergoing percutaneous coronaryinterventions (PCI) in randomized controlled trials (RCTs). METHODS: We searched Medline, EMBASE, Cochrane Library, CNKI, VIP and relevant websites ( https://scholar-google com.ezproxy.lib.usf.edu/ ) for articles to compare outcomes between everolimus eluting stent and paclitaxel-eluting stent without language or date restriction. RCTs that compared the use of everolimus -eluting stent and paclitaxel-eluting stent in PCI were included. Variables relating to patient, study characteristics, and clinical endpoints were extracted. Meta-analysis was performed using RevMan 5.2 software. RESULTS: We identified 6 published studies (from three randomized trials) more on everolimus-eluting stent (n = 3352) than paclitaxel-eluting (n = 1639), with follow-up duration ranging from 3, 4 and 5 years. Three-year outcomes of everolimus-eluting stent compared to paclitaxel-eluting were as following: the everolimus-eluting stent significantly reduced all-cause death (relative risk [RR]:0.63; 95% confidence interval [CI]: 0.46. to 0.82), MACE (RR: 0.56; 95% CI: 0.41 to 0.77), MI (RR: 0.64; 95% CI: 0.48 to 0.86), TLR (RR: 0.72; 95% CI: 0.59 to 0.88), ID-TLR (RR: 0.74; 95% CI: 0.59 to 0.92) and ST (RR: 0.54; 95% CI: 0.32 to 0.90). There was no difference in TVR between the everolimus-eluting and paclitaxel-eluting (RR: 0.76; 95% CI: 0.58 to 1.10); Four-year outcomes of everolimus-eluting compared to paclitaxel-eluting: the everolimus-eluting significantly reduced MACE (RR: 0.44; 95% CI: 0.18 to 0.98) and ID-TLR (RR: 0.47; 95 % CI: 0.23 to 0.97). There was no difference in MI (RR: 0.48; 95% CI: 0.16 to 1.46), TLR (RR: 0.46; 95% CI: 0.20 to 1.04) and ST ((RR: 0.34; 95% CI: 0.05 to 2.39). Five-year outcomes of everolimus-eluting stent compared to paclitaxel eluting: There was no difference in ID-TLR (RR: 0.67; 95% CI: 0.45 to 1.02) and ST (RR: 0.71; 95% CI: 0.28 to 1.80). CONCLUSIONS: In the present meta-analysis, everolimus-eluting appeared to be safe and clinically effective in patients undergoing PCI in comparison to PES in 3-year clinical outcomes; there was similar no difference in reduction of ST between EES and PES in long-term(>= 4 years) clinical follow-ups. Everolimus-eluting is more safety than paclitaxel eluting in long-term clinical follow-ups, whether these effects can be applied to different patient subgroups warrants further investigation. PMID- 26860587 TI - Racial and ethnic variations in phthalate metabolite concentration changes across full-term pregnancies. AB - Higher concentrations of certain phthalate metabolites are associated with adverse reproductive and pregnancy outcomes, as well as poor infant/child health outcomes. In non-pregnant populations, phthalate metabolite concentrations vary by race/ethnicity. Few studies have documented racial/ethnic differences between phthalate metabolite concentrations at multiple time points across the full course of pregnancy. The objective of the study was to characterize the change in phthalate metabolite concentrations by race/ethnicity across multiple pregnancy time points. Women were participants in a prospectively collected pregnancy cohort who delivered at term (>=37 weeks) and had available urinary phthalate metabolite concentrations for >=3 time points across full-term pregnancies (n=350 women). We assessed urinary concentrations of eight phthalate metabolites that were log-transformed and specific gravity-adjusted. We evaluated the potential racial/ethnic differences in phthalate metabolite concentrations at baseline (median 10 weeks gestation) using ANOVA and across pregnancy using linear mixed models to calculate the percent change and 95% confidence intervals adjusted for sociodemographic and lifestyle factors. Almost 30% of the population were non Hispanic black or Hispanic. With the exception of mono-(3-carboxypropyl) (MCPP) and di-ethylhexyl phthalate (DEHP) metabolites, baseline levels of phthalate metabolites were significantly higher in non-whites (P<0.05). When evaluating patterns by race/ethnicity, mono-ethyl phthalate (MEP) and MCPP had significant percent changes across pregnancy. MEP was higher in Hispanics at baseline and decreased in mid-pregnancy but increased in late pregnancy for non-Hispanic blacks. MCPP was substantially higher in non-Hispanic blacks at baseline but decreased later in pregnancy. Across pregnancy, non-Hispanic black and Hispanic women had higher concentrations of certain phthalate metabolites. These differences may have implications for racial/ethnic differences in adverse pregnancy and child health outcomes. PMID- 26860588 TI - PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells. AB - LF11-322 (PFWRIRIRR-NH2) (PFR peptide), a nine amino acid-residue peptide fragment derived from human lactoferricin, possesses potent cytotoxicity against bacteria. We report here the discovery and characterization of its antitumor activity in leukemia cells. PFR peptide inhibited the proliferation of MEL and HL 60 leukemia cells by inducing cell death in the absence of the classical features of apoptosis, including chromatin condensation, Annexin V staining, Caspase activation and increase of abundance of pro-apoptotic proteins. Instead, necrotic cell death as evidenced by increasing intracellular PI staining and LDH release, inducing membrane disruption and up-regulating intracellular calcium level, was observed following PFR peptide treatment. In addition to necrotic cell death, PFR peptide also induced G0/G1 cell cycle arrest. Moreover, PFR peptide exhibited favorable antitumor activity and tolerability in vivo. These findings thus provide a new clue of antimicrobial peptides as a potential novel therapy for leukemia. PMID- 26860590 TI - Few layer epitaxial germanene: a novel two-dimensional Dirac material. AB - Monolayer germanene, a novel graphene-like germanium allotrope akin to silicene has been recently grown on metallic substrates. Lying directly on the metal surfaces the reconstructed atom-thin sheets are prone to lose the massless Dirac fermion character and unique associated physical properties of free standing germanene. Here, we show that few layer germanene, which we create by dry epitaxy on a gold template, possesses Dirac cones thanks to a reduced interaction. This finding established on synchrotron-radiation-based photoemission, scanning tunneling microscopy imaging and surface electron diffraction places few layer germanene among the rare two-dimensional Dirac materials. Since germanium is currently used in the mainstream Si-based electronics, perspectives of using germanene for scaling down beyond the 5 nm node appear very promising. Other fascinating properties seem at hand, typically the robust quantum spin Hall effect for applications in spintronics and the engineering of Floquet Majorana fermions by light for quantum computing. PMID- 26860591 TI - Re: Is it reasonable to use 1 and 8 kHz anchor points in the medico-legal diagnosis and estimation of noise-induced hearing loss? PMID- 26860592 TI - Validity and reliability of the French translation of the VISA-A questionnaire for Achilles tendinopathy. AB - PURPOSE: The Victorian Institute of Sport Assessment - Achilles tendinopathy questionnaire (VISA-A) evaluates the clinical severity of Achilles tendinopathy. The aim of this study was to translate the VISA-A into French and to study the reliability and validity of this French version, the VISA-AF. METHOD: The VISA-A was translated into French to produce the VISA-AF using a validated methodology in six steps. Thereafter, several psychometric properties of this French version such as test-retest reliability, internal consistency, construct validity and floor and ceiling effects were evaluated. Therefore, we recruited 116 subjects, distributed into 3 groups: pathological patients (n = 31), at-risk athletes (n = 63) and healthy people (n = 22). RESULTS: The final version of the VISA-AF was approved by an expert committee. On a scale ranging from 0 to 100, the average scores of the VISA-AF obtained were 59 (+/- 18) for the pathological group, 99 (+/- 1) for the healthy group and 94 (+/- 7) for the at-risk group. The VISA-AF shows excellent reliability, low correlations with the discriminant subscales of the SF-36 and moderate correlations with the convergent subscales of the SF-36. CONCLUSIONS: The French version of the VISA-A is equivalent to its original version and is a reliable and valid questionnaire for French-speaking patients with Achilles tendinopathy. Implication for Rehabilitation The VISA-AF questionnaire is a reliable translation of the original VISA-A, from English into French, which is one of the most widespread languages in the world. The VISA-AF questionnaire is now a valid instrument that can be used by clinicians and researchers to assess the severity of pain and disability of French-speaking subjects with Achilles tendinopathy. The VISA-AF is a questionnaire to assess the severity of Achilles tendinopathy symptoms but is not a diagnostic tool. PMID- 26860589 TI - Detection and treatment of omega-3 fatty acid deficiency in psychiatric practice: Rationale and implementation. AB - A body of translational evidence has implicated dietary deficiency in long-chain omega-3 (LCn-3) fatty acids, including eicosapenaenoic acid (EPA) and docosahexaenoic acid (DHA), in the pathophysiology and potentially etiology of different psychiatric disorders. Case-control studies have consistently observed low erythrocyte (red blood cell) EPA and/or DHA levels in patients with major depressive disorder, bipolar disorder, schizophrenia, and attention deficit hyperactivity disorder. Low erythrocyte EPA + DHA biostatus can be treated with fish oil-based formulations containing preformed EPA + DHA, and extant evidence suggests that fish oil supplementation is safe and well-tolerated and may have therapeutic benefits. These and other data provide a rationale for screening for and treating LCn-3 fatty acid deficiency in patients with psychiatric illness. To this end, we have implemented a pilot program that routinely measures blood fatty acid levels in psychiatric patients entering a residential inpatient clinic. To date over 130 blood samples, primarily from patients with treatment-refractory mood or anxiety disorders, have been collected and analyzed. Our initial results indicate that the majority (75 %) of patients exhibit whole blood EPA + DHA levels at <= 4 percent of total fatty acid composition, a rate that is significantly higher than general population norms (25 %). In a sub-set of cases, corrective treatment with fish oil-based products has resulted in improvements in psychiatric symptoms without notable side effects. In view of the urgent need for improvements in conventional treatment algorithms, these preliminary findings provide important support for expanding this approach in routine psychiatric practice. PMID- 26860593 TI - Validity and reliability of a novel Color-Risk Psychiatric Triage in a psychiatric emergency department. AB - BACKGROUND: Classification of Psychiatric Emergency Presentations (PEP) is not sufficiently clear due to their inherent high inter-subjectivity and lack of validated triage instruments. In order to improve current classification of psychiatric emergency presentations (PEP) at Emergency Departments, we implemented and validated the Color-Risk Psychiatric Triage (CRPT), an instrument for classifying PEP risk by sorting one to five color/risk levels and one to thirty-two possible conditions arranged by risk. METHODS: Users who visited the Emergency Department (ED) of a Mexican psychiatric hospital from Dec 1st, 2008 to Dec 1st, 2009 were included. One CRPT was assessed by an ED psychiatrist to each patient upon their arrival to ED. Some patients were randomly assessed simultaneously with an additional CRPT and a Crisis and Triage Rating Scale (CTRS) to test validity and reliability of the CRPT. RESULTS: A total of 7,631 CRPT assessments were included. The majority of PEP were non-urgent (74.28 %). For the validation phase n = 158 patients were included. CRPT score showed higher concurrent validity than CRPT color/risk. CRPT level/risk and score showed highest concurrent validity within dangerousness domain of CTRS (r = 0.703, p < 0.0001). CRPT and CTRS scores showed similar predictive validity (p < 0.0001). High intraclass correlation coefficient (0.982) and Cohen's Kappa (0.89) were observed for CRPT score (r = 0.982, p < 0.0001). CONCLUSIONS: CRPT appeared to be a useful instrument for PEP classification due to its concurrent validity, predictive validity and reliability. CRPT score showed higher correlations than the CRPT color/risk. The five levels of risk provided by the CRPT appear to represent a simple and specific method for classifying PEP. This approach considers actual or potential risk, rather than severity, as the main factor for sorting PEP, which improves upon the current approach to emergency classification that is mainly based on the criterion of severity. Regardless of the triage procedure, emergency assessments should no longer classify PEP as "not real emergencies." PMID- 26860594 TI - Implementing research results in clinical practice- the experiences of healthcare professionals. AB - BACKGROUND: In healthcare research, results diffuse only slowly into clinical practice, and there is a need to bridge the gap between research and practice. This study elucidates how healthcare professionals in a hospital setting experience working with the implementation of research results. METHOD: A descriptive design was chosen. During 2014, 12 interviews were carried out with healthcare professionals representing different roles in the implementation process, based on semi-structured interview guidelines. The analysis was guided by a directed content analysis approach. RESULTS: The initial implementation was non-formalized. In the decision-making and management process, the pattern among nurses and doctors, respectively, was found to be different. While nurses' decisions tended to be problem-oriented and managed on a person-driven basis, doctors' decisions were consensus-oriented and managed by autonomy. All, however, experienced a knowledge-based execution of the research results, as the implementation process ended. CONCLUSION: The results illuminate the challenges involved in closing the evidence-practice gap, and may add to the growing body of knowledge on which basis actions can be taken to ensure the best care and treatment available actually reaches the patient. PMID- 26860595 TI - Zinc oxide nanoparticles induce renal toxicity through reactive oxygen species. AB - Nanoparticles of zinc oxide (ZnO NPs) are applied in many fields nowadays. Consequently, concerns have been raised about its potential harmful effects. The present study focuses on its toxic effect on podocytes and rats. In vitro study, podocytes were treated with different concentrations of ZnO NPs (10, 50 and 100 MUg/ml), the viability of cells was decreased as time prolonged according to MTT assay. Meantime, flow cytometry analysis indicated that ZnO NPs induced intracellular accumulation of reactive oxygen species (ROS) and apoptosis. The measurement of superoxide dismutase (SOD) and malondialdehyde (MDA) showed that ZnO NPs decreased SOD level and increased MDA level. Interestingly, pretreatment with N-mercaptopropionyl-glycine, known as a type of ROS scavenger, could inhibit podocyte apoptosis induced by ZnO NPs. Meantime, a loss of nephrin can be detected, which may result in a direct damage to slit diaphragms. In vivo study, adult male Wistar rats were administrated with 3mg/kg/day ZnO NPs for 5 days, body weight and kidney index were significantly reduced. In addition, ZnO NPs decreased the activity of catalase and SOD in kidney cortex in vivo. It could be concluded that ZnO NPs present toxic effect on podocytes and Wistar rats, which was related with oxidative stress. PMID- 26860596 TI - [Validation of the Seven Minute Screen for use in a memory clinic]. AB - Cognitive tests play a crucial part in the assessment of dementia. In 1998 the Seven Minute Screen was developed by Solomon and colleagues. The test was originally designed to distinguish between Alzheimer's disease (AD) and normal ageing, and research showed that the instrument is highly sensitive to AD. Subsequent research also proved the diagnostic accuracy of the Seven Minute Screen in the detection of other common types of dementia, such as vascular dementia, frontotemporal dementia and dementia with Lewy bodies. This article reports new research on the predictive validity of the Seven Minute Screen using 289 cognitively intact subjects, 175 patients with MCI and 563 patients with dementia in the setting of a memory clinic. In addition, a comparison is made with the Mini Mental State Examination (MMSE). The study demonstrates that the Seven Minute Screen is a valuable screening instrument for all common types of dementia, and it has added value to the MMSE. The sensitivity for dementia is 96 % and the specificity 93 %, in comparison to 69 and 98 % for the MMSE (< 24). The sensitivity for the various types of dementia is consistently high, ranging from 92 % for a subcortical dementia to 97 % for AD. The Seven Minute Screen requires little training, and combines a short administration time with a high diagnostic accuracy. This makes the Seven Minute Screen useful for application in memory clinics. PMID- 26860598 TI - Restoration of ulnar nerve motor function by pronator quadratus motor branch: an anatomical study. AB - BACKGROUND: The traditional surgical approach to repair of brachial plexus lesions involves use of whole segment ulnar nerve graft for contralateral seventh cervical (cC7) nerve root transfer, which sabotages the possibility of ulnar nerve recovery. We assessed the anatomical feasibility of a new approach that involves preservation of the motor branch of ulnar nerve (MBUN), for a later stage repair using the recovered pronator quadratus motor branch (PQMB), subsequent to the cC7 transfer procedure. METHODS: Twenty-seven adult cadaver arms and one side of fresh adult cadaver were used in this study. The anterior interosseous nerve and its PQMB, as well as the motor and sensory branches of the ulnar nerve were dissected. The distances from the end of PQMB to the mid-point of a line joining the radial styloid and ulnar styloid, as well as to the point of divergence of the ulnar nerve, were measured. The MBUN was dissected from distal to proximal and the maximum length was measured. The diameter and number of axons of the nerve branches were also recorded. RESULTS: The distance from the end of the PQMB to the midpoint of the radial styloid and ulnar styloid was 6.04 +/- 0.52 cm, and that to the point of divergence of the ulnar nerve was 8.02 +/- 0.63 cm. The maximum length of the MBUN after its dissociation was 9.70 +/- 1.38 cm. The mean diameters of axons of the MBUN and PQMB were 0.09 +/- 0.02 cm and 0.05 +/- 0.01 cm, respectively. The corresponding mean numbers of axons were 2913 +/- 624 and 757 +/- 183, respectively. CONCLUSIONS: The results indicate that the PQMB is suitable for transferring to the MBUN without nerve graft. This anatomical study paves the way for further testing of this new procedure after cC7 transfer in clinical settings. PMID- 26860600 TI - Comparison of surgical exposure and maneuverability associated with microscopy and endoscopy in the retrolabyrinthine and transcrusal approaches to the retrochiasmatic region: a cadaveric study. AB - BACKGROUND: The retrolabyrinthine and transcrusal approaches (RLA and TCA, respectively) are the two most often used posterior transpetrosal approaches that are used to treat lesions in the retrochiasmatic region. Endoscopes are increasingly used in neurosurgical practice. To determine whether a difference exists between the two transpetrosal approaches in the retrochiasmatic region, we evaluated and compared the exposure and maneuverability associated with the microscope and the endoscope in these approaches. METHODS: Seven formalin-fixed cadaveric heads were dissected bilaterally through the two approaches: four for evaluation and three injected with colored latex for photography. The retrochiasmatic region was divided into four sub-compartments: the compartment before the infundibulum, which was further divided into two parts, (1) the ipsilateral and (2) the contralateral compartments; (3) the retroinfundibulum compartment; (4) the third ventricle. After each approach, exposure and maneuverability of the structures in these four compartments obtained by microscopy and endoscopy were scored under a guidance of a numerical grading system for further comparison. RESULTS: The TCA provided better exposure and maneuverability at the retrochiasmatic region than the RLA in both the microscopy model [scores of 39.75 +/- 2.12 and 32.38 +/- 2.56 respectively (p < 0.05)] and the endoscopy model [scores of 82.13 +/- 3.40 and 43.75 +/- 1.67 respectively (p < 0.05)]. CONCLUSIONS: The TCA is better than the RLA at offering exposure and manipulation to structures in the retrochiasmatic region, especially in patients whose lesion is located high into the third ventricle and/or expanded into the contralateral part. Endoscopes may be helpful in TCA in terms of exposing and maneuvering structures in the contralateral and interpeduncle fossa areas. However, in RLA, not enough room is available for simultaneously maneuvering an endoscope and a surgical instrument. PMID- 26860601 TI - BBMRI-ERIC: the novel gateway to biobanks. From humans to humans. AB - BBMRI-ERIC, the Biobanking and BioMolecular Resources Research Infrastructure European Research Infrastructure Consortium, is a new form of umbrella organization for biobanking in Europe. For rare and common diseases alike, it aims at providing fair access to quality-controlled human biological samples and associated biomedical and biomolecular data. Such access enables basic mechanisms underlying diseases to be studied, which is indispensable for the development of new biomarkers and drugs. In the context of the European Research Area (ERA), biobanks, which were identified as a particular European strength, contribute to Europe's cohesion policy through capacity-building in the BBMRI-ERIC member countries. PMID- 26860602 TI - Results of surgical treatment in patients with sulcus vocalis. AB - Sulcus vocalis is one of the most difficult to treat benign vocal fold pathologies. Ford distinguished three types of sulci: I- superficial, II- vergeture and III- true sulcus vocalis. The aim of the study was to assess the results of surgical treatment in patients with sulcus vocalis. Material of the study consisted of 24 patients with type II (16 subjects) and type III sulcus (8 subjects). METHODS: Videostroboscopy, perceptual voice assessment and objective acoustic voice analysis were performed before surgery and at 8 months of follow up. All patients underwent surgical treatment as well as pre- and postsurgical voice therapy. RESULTS: Postsurgical stroboscopic examination showed statistically significant differences in symmetry and regularity of vibrations. Subjective perceptual voice assessment showed improvement in the grade of voice hoarseness, roughness, breathiness and strain. Objective voice analysis showed statistically significant difference only in jita parameter, in contrast to other examined parameters--although their values decreased after surgery, the change was not statistically significant. CONCLUSIONS: Surgical treatment of sulcus should be considered in patients with severe voice problems; however, the end results are not always entirely satisfactory. PMID- 26860603 TI - Evaluation of risk factors for oral cavity and oropharynx cancers in patients under the week activity program of head and neck cancers prevention in Lodz. AB - INTRODUCTION: The aim of the study was to evaluate risk factors for oral cavity and oropharynx cancers in patients under the week activity program of head and neck cancers prevention in Lodz. MATERIAL AND METHODS: 104 people reported to preventive examinations under the week activity program of head and neck cancers prevention in Lodz (25-th of September, 2015): 33 women aged 21-68 and 38 men aged 23-71. Before ENT examination, subjects completed the questionnaire, which concerned: the degree of education, source of information about preventive examinations, symptoms, smoking, number of smoked cigarettes, alcohol, number of life sexual partners, number of oral sex partners and family history of head and neck cancers. RESULTS AND CONCLUSIONS: The analysis showed that people who reported to preventive examination were mostly in the age group of 51-60 and over 60, respectively 71,2% of women and 57,9% of men. Patients were at the age, that predispose to oral cavity and oropharynx cancers. In our own material, 15,9% of women and 23,6% of men have smoked. Most of them have smoked 10-20 cigarettes daily. On the other hand, 40,9% of women and 10,5% of men didn't consume alcohol. In our study, both women and men had, at life, 1-3 sexual partners the most often, respectively 78,9% and 60,5%. The oral sex was cultivated by 45,5% of women and 60,5% of men, the most often with 1-3 partners, respectively 95,8% and 70,0%. Based on complete ENT examination and the presence of risk factors for oral cavity and oropharynx cancers, 14,4% of patients were qualified to further oncological examinations including: videolaryngostroboscopy, neck ultrasound with fine-needle biopsy, neck CT and HPV test. PMID- 26860604 TI - Snoring but not BMI influences aggressive behavior and concentration problems in children. AB - INTRODUCTION: Sleep-disordered breathing is an important risk factor for neurobehavioral impairment in children. This study was conducted to estimate the prevalence of sleep-disordered breathing in a population of first graders and to determine the association between behavior problems, body mass index (BMI) and snoring. MATERIAL AND METHODS: A population-based, cross-sectional study was conducted using a parent-reported questionnaire. The study evaluated 2,474 first graders. Data including age, weight, height, BMI, snoring intensity, and problems with child behavior were analyzed. RESULTS: Of 3,480 eligible children, 2,474 (71.1%) returned completed questionnaires. Of these, 72% were reported to be non snorers, 28% snorers, and 6.4% habitual snorers. There was a positive linear association between behavior impairment and snoring severity measured on a 5 point scale, with highly significant differences between each of five snoring intensity groups (p<0.00001). Compared to non-snorers, snorers in the normal weight and overweight subgroups had significantly more aggressive behavior (p<0.0001; p=0.002, respectively) and more concentration problems (p<0.0001; p=0.03, respectively). There was no significant difference in aggressive behavior and concentration problems intensity in the screened groups of obese and normal subjects (p=0.70; p=0.79, respectively). DISCUSSION: Behavior problems were positively associated with increasing snoring frequency. However, there were no differences in the prevalence of behavioral or concentration problems between obese and non-obese first-graders studied. PMID- 26860605 TI - Deposition of intranasal glucocorticoids--preliminary study. AB - INTRODUCTION: Intranasal glucocorticoids are the treatment of choice in the therapy of rhinitis. The differences in efficiency of particular medications proven by therapeutic index may result from differences in composition of particular formulations as well as from diverse deposition in nasal cavities. Intranasal formulations of glucocorticoids differ in volume of a single dose in addition to variety in density, viscosity and dispenser nozzle structure. The aim of this report was to analyze the deposition of most often used intranasal glucocorticoids in the nasal cavity and assessment of the usefulness of a nose model from a 3D printer reflecting anatomical features of a concrete patient. MATERIAL AND METHODS: Three newest and most often used in Poland intranasal glucocorticoids were chosen to analysis; mometasone furoate (MF), fluticasone propionate (FP) and fluticasone furoate (FF). Droplet size distribution obtained from the tested formulations was determined by use of a laser aerosol spectrometer Spraytec (Malvern Instruments, UK). The model of the nasal cavity was obtained using a 3D printer. The printout was based upon a tridimensional reconstruction of nasal cavity created on the basis of digital processing of computed tomography of paranasal sinuses. The deposition of examined medications was established by a method of visualization combined with image analysis using commercial substance which colored itself intensively under the influence of water being the dominant ingredient of all tested preparations. On the basis of obtained results regions of dominating deposition of droplets of intranasal medication on the wall and septum of the nasal cavity were compared. RESULTS: Droplet size of aerosol of tested intranasal medications typically lies within the range of 25-150 um. All tested medications deposited mainly on the anterior part of inferior turbinate. FP preparation deposited also on the anterior part of the middle nasal turbinate, marginally embracing a fragment of the central part of this turbinate as well together with deposition in the middle and superior nasal meatus reaching the region of nasal ceiling and olfactory field. MF preparation deposited on the anterior part of the inferior turbinate and central part of this turbinate alike. The area of mucous membrane of lateral wall of nasal cavity on which MF deposited was similar to the area achieved after the application of FP preparation but much greater than in the case of FF preparation. FF drug deposition concentrates only on the anterior part of the inferior turbinate. Despite directing the drug to the lateral wall of the nasal cavity a great proportion of examined preparations deposit also on the nasal septum. CONCLUSIONS: The practical application of tridimensional representation (3D printout) of actual geometry of nasal cavity to establish the deposition of inGKS was proven. Droplet size and the geometry of the aerosol cloud introduced into the nostril determine the significant deposition of medication droplets in the anterior part of the nasal cavity. Both physical properties of the drug as well as spraying system applied influence spatial distribution of the drug. The interaction of the air flow with the layer of deposited fluid plays a major role in the deposition of the drug in the nasal cavity, therefore it is so important that the drug does not drain by gravity but remains at the site of deposition which may be reinforced by thixotropic properties of the preparation. PMID- 26860606 TI - Is ventilation tube insertion necessary in children with otitis media with effusion? AB - OBJECTIVES: To compare audiological outcomes of ventilation tube insertion(VTI) and myringotomy alone in association with adenoidectomy in patient with otitis media with effusion(OME). STUDY DESIGN: Retrospective clinical chart review. SUBJECTS AND METHODS: In total, 148 patients (78 male, 70 female; average age of 6,02 +/- 1,98 years, range 4 to 7 years) who had been underwent adenoidectomy in association with VTI or myringotomy alone in our clinic were included in this study. Demographics and audiological outcomes were collected. The patients were divided randomly into two groups, group A (72) were subjected to adenoidectomy with VTI and group B (76) were subjected to adenoidectomy with myringotomy. Audiological outcomes comparing the both groups at six months also continued to patients follow up to one year after surgery. Results with a p-value <0.05 were considered statistically significant. RESULTS: The mean pure tone hearing threshold preoperatively in group A was 28.68 +/- 11.72 dB, while it was 24.25 +/ 12.68 dB in group B. At postoperative six months, the means in group A were 8.4 +/- 2,32 dB, while the means were 10,4 +/- 3,36 dB in group B. Statistical analysis showed statistically significant difference between the means of pure tone hearing thresholds in both groups during the whole follow up period (p<0.05). CONCLUSION: Our data suggest audiological outcomes of VTI was higher compared with myringotomy alone in association with adenoidectomy. However, further studies with a higher number of patients are needed to compare the audiological outcomes of various ventilation tubes types. PMID- 26860607 TI - Factors predicting early diagnosis of pediatric laryngotracheobronchial foreign bodies. AB - OBJECTIVE: To study the clinical and radiological findings to make early diagnosis of foreign body (FB) aspiration in children. METHODS: This prospective study was conducted on 45 children below 12 years of age with a clinical diagnosis of FB aspiration undergone rigid bronchoscopy from September 2008 to may 2010. RESULTS: Bronchoscopy was positive for FB in 37 children. The results of these 37 children (15 female and 22 male) were analyzed. 81% of children were in age group of 1-3 years. Penetration syndrome (sudden onset coughing, choking and gagging when the child is having something in the mouth) (89.2%) and decreased breath sounds (86.5%) were the most common clinical features. Cough, respiratory difficulty and fever were present in 83.8%, 78.4% and 27% respectively. Tachypnoea, tachycardia, chest retractions, decreased chest movements and wheeze were present in 83.3%, 83.3%, 83.3%, 51.4% and 43.2% respectively. Unilateral hyperinflation (64.9%), mediastinal shift (45.9%), and collapse (21.6%) were common radiological sign on chest radiograph and in 13.5% patients the chest X-rays were normal. Sites of FB lodgments were larynx, trachea, right main bronchus, left main bronchus and bilateral bronchi in 10.8%, 10.8%, 35.1%, 37.8 and 5.5% respectively. Food related FBs were present in 30 cases (peanut in 54.1%) and inorganic FBs were present in 7 cases. FBs were removed successfully by rigid bronchoscopy in all cases without any mortality. CONCLUSIONS: Penetration syndrome, localized decreased breath sounds, unilateral hyperinflation and/or mediastinal shift on radiology are predictors for early diagnosis of FB aspiration. PMID- 26860608 TI - Ethmoid roof radiology; analysis of lateral lamella of cribriform plate. AB - OBJECTIVE: We evaluated the extent of asymmetry evident in paranasal sinus computed tomography (CT) scans of Turkish patients without sinusitis in the ethmoid roof. Our data contribute to the body of knowledge on the subject. MATERIALS AND METHODS: We retrospectively studied multiplanar reformatted CT images of the paranasal sinus (1-mm sections) from 110 patients (50 male, 60 female). Ethmoid roof variations on either side were compared and the lateral lamellar length of the cribriform plate was measured. The results were scored using the Keros classification. RESULTS: The lateral lamella of the cribriform plate averaged 5.78 mm in height on the right side and 5.98 mm on the left. The most common Keros type was type 2 (67.72%), followed by type 3 (22.28%), and type 1 (10%). Keros asymmetry (>= 0.01 mm, affecting either side) was apparent in all patients (48.2% right-sided and 51.8% left-sided). RESULTS: Preoperatively, paranasal sinus CT scans should be evaluated carefully to eliminate the possibility of life-threatening complications, including intracranial trauma, which may develop during endoscopic sinus surgery; the left and right sides of the ethmoid roof may differ in depth. PMID- 26860609 TI - Gastroesophageal reflux disease with proton pump inhibitor use is associated with an increased risk of osteoporosis: a nationwide population-based analysis. AB - Gastroesophageal reflux disease (GERD) with proton pump inhibitor (PPI) use is associated with an increased risk of osteoporosis. The risk of hip fracture is not increased in GERD patients with PPI use. INTRODUCTION: The relationship between GERD with PPI treatment and the risk of osteoporosis is unclear. We aimed to determine the risk of developing osteoporosis in patients diagnosed with GERD. METHODS: Patients diagnosed with GERD and received PPI treatment between 2000 and 2010 were identified from the Longitudinal Health Insurance Database as the study cohort (n = 10,620), which was frequency matched with the comparison cohort (n = 20,738) sampled from the general population according to age, sex, index year, and comorbidities. Both cohorts were followed until the end of 2011. The risk of osteoporosis was evaluated in both groups by using Cox proportional hazards regression models. RESULTS: The GERD patients with PPI treatment had a greater incidence (31.4 vs 20.7 per 1000 person-year; crude hazard ratio [cHR] 1.51; 95 % confidence interval [CI] 1.40-1.63) and a higher risk (adjusted HR [aHR] 1.50; 95 % CI 1.39-1.62) of osteoporosis than that of the comparison cohort. However, the overall incidence of hip fracture was not different between the GERD with PPI use and the control cohorts (aHR 0.79; 95 % CI 0.53-1.18). CONCLUSION: GERD with PPI use is associated with an increased risk of osteoporosis. The findings of our study do not support an increased risk of hip fracture in GERD patients treated with a PPI. PMID- 26860610 TI - The Brazilian version of the three-factor eating questionnaire-R21: psychometric evaluation and scoring pattern. AB - PURPOSE: This study aimed to evaluate the psychometric properties and scoring pattern of the Brazilian version of the three-factor eating questionnaire-r21 (TFEQ-R21). METHODS: Data were collected from 410 undergraduate students. Confirmatory factor analysis was conducted to examine the factor structure of the TFEQ-R21. Convergent and discriminant validity also was assessed. Cluster analysis was performed to investigate scoring patterns. RESULTS: In assessing the quality setting, the model was considered satisfactory (chi 2/gl = 2.24, CFI = 0.97, TLI = 0.96, RMSEA = 0.05). The instrument was also considered appropriate in relation to the discriminant and convergent validity. There was a positive correlation between body mass index and the dimensions of cognitive restraint (r s = 0.449, p < 0.001) and emotional eating (r s = 0.112, p = 0.023). Using cluster analysis three respondent profiles were identified. The profile "A" was associated with appropriate weight, the "B" was characterized by high scores in cognitive restraint dimension, and the cluster "C" focused individuals who had higher scores on the uncontrolled eating and emotional eating dimensions. CONCLUSIONS: The Brazilian version of TFEQ-R21 has adequate psychometric properties, and the identified response profiles offer a promising prospect for its use in clinical practice, in weight loss interventions. PMID- 26860611 TI - The Emerging Roles of Leadless Devices. AB - OPINION STATEMENT: The role of leadless devices to treat cardiac rhythm disorders and heart failure is emerging. Subcutaneous defibrillator (S-ICD) and leadless pacemakers were developed to ameliorate the risks associated with chronic transvenous leads. Potential benefits of leadless pacemakers and S-ICD include more favorable infection profile, less risk of venous stenosis or occlusion, and less risk of tricuspid valve insufficiency. Novel implantable leadless monitors for heart failure represent a novel diagnostic tool that can guide therapy for CHF. PMID- 26860612 TI - Evaluation of the impact of fibromyalgia in disease activity and treatment effect in spondyloarthritis. AB - BACKGROUND: Fibromyalgia (FM) can coexist with Spondyloarthritis (SpA) leading to diagnostic and treatment dilemmas, especially in the presence of enthesitis. With this study we aimed to estimate the prevalence of FM in SpA and to compare the clinical/disease features and TNF inhibitors (TNFi) in patients with/without FM. METHOD: FM was defined by a score = > 5/6 of the Fibromyalgia Rapid Screening Tool (FiRST). SpA patients (according to the rheumatologist) and consecutively consulting in the day care hospital but also in the outpatient clinic at the rheumatology department of a tertiary care university hospital were included. Demographics, disease characteristics, activity and severity and TNFi treatment were compared in patients with and without FM; retention rate of the first TNFi and associated factors were explored (Kaplan Meier and Cox regression). RESULTS: Of the 196 enrolled SpA patients, 42 (21.4 %) were positively screened for FM. No statistically significant differences in the prevalence of FM were found with regard to the fulfillment of the ASAS criteria for peripheral/axial SpA, nor with regard to the fulfillment of the imaging vs. clinical arm of the ASAS criteria. However, patients with coexisting FM presented significantly with more enthesitis, higher disease activity (BASDAI and VAS) and poorer function scores (BASFI). No differences were found with regard to the initiation of TNFi treatment (79.0 % vs. 70.0 %, respectively), but the retention rate of the first TNFi after 2 years was shorter in the group of patients with FM (28.1 % (95 % CI 12.5-44.0) vs. 41.7 % (95 % CI 32.2-51.3), p = 0.01). CONCLUSION: This study confirms that coexistent FM in SpA might impact the patient-reported outcome indices for disease activity and function, and the retention rate of TNFi treatment. PMID- 26860613 TI - Integrated foam fractionation for heterologous rhamnolipid production with recombinant Pseudomonas putida in a bioreactor. AB - Heterologeous production of rhamnolipids in Pseudomonas putida is characterized by advantages of a non-pathogenic host and avoidance of the native quorum sensing regulation in Pseudomonas aeruginosa. Yet, downstream processing is a major problem in rhamnolipid production and increases in complexity at low rhamnolipid titers and when using chemical foam control. This leaves the necessity of a simple concentrating and purification method. Foam fractionation is an elegant method for in situ product removal when producing microbial surfactants. However, up to now in situ foam fractionation is nearly exclusively reported for the production of surfactin with Bacillus subtilis. So far no cultivation integrated foam fractionation process for rhamnolipid production has been reported. This is probably due to excessive bacterial foam enrichment in that system. In this article a simple integrated foam fractionation process is reported for heterologous rhamnolipid production in a bioreactor with easily manageable bacterial foam enrichments. Rhamnolipids were highly concentrated in the foam during the cultivation process with enrichment factors up to 200. The described process was evaluated at different pH, media compositions and temperatures. Foam fractionation processes were characterized by calculating procedural parameter including rhamnolipid and bacterial enrichment, rhamnolipid recovery, YX/S, YP/X, and specific as well as volumetric productivities. Comparing foam fractionation parameters of the rhamnolipid process with the surfactin process a high effectiveness of the integrated foam fractionation for rhamnolipid production was demonstrated. PMID- 26860614 TI - Mechanisms of SNR and line shape improvement by B0 correction in overdiscrete MRSI reconstruction. AB - PURPOSE: Inhomogeneities of the main magnetic field cause line broadening and location-dependent frequency shifts in brain MRSI. These are often visible despite advanced B0 shimming. The purpose of this work is to propose an advanced B0 correction method that can easily be applied during postprocessing. METHODS: A target-driven overdiscrete reconstruction method previously introduced for MRSI is modified by dividing it into two steps. In a first step, an intermediate spectroscopic image with arbitrarily high resolution is generated, on which B0 correction is performed as an additional processing step based on an additionally acquired B0 map. This frequency-aligns metabolite peaks and destroys noise correlations between neighboring subvoxels. Second, the voxel is shaped by application of the spatial response target. The method was tested with simulated spectroscopic imaging data as well as in a series of MRSI data sets obtained from four healthy volunteers at 7T. RESULTS: A systematic gain in spectral signal-to noise ratio is achieved, due to spatial averaging now occurring over peak aligned and noise decorrelated subvoxel spectra. At the same time, metabolite peak line widths are reduced. CONCLUSION: In the presence of B0 inhomogeneities across the field of view, the proposed method offers the potential to improve spectral quality with only a minimal additional effort during acquisition. Magn Reson Med 77:44-56, 2017. (c) 2015 Wiley Periodicals, Inc. PMID- 26860616 TI - Alcohol withdrawal induces long-lasting spatial working memory impairments: relationship with changes in corticosterone response in the prefrontal cortex. AB - This study intends to determine whether long-lasting glucocorticoids (GCs) dysregulation in the prefrontal cortex (PFC) or the dorsal hippocampus (dHPC) play a causal role in the maintenance of working memory (WM) deficits observed after alcohol withdrawal. Here, we report that C57/BL6 male mice submitted to 6 months alcohol consumption (12 percent v/v) followed by 1 (1W) or 6 weeks (6W) withdrawal periods exhibit WM deficits in a spatial alternation task and an exaggerated corticosterone rise during and after memory testing in the PFC but not the dHPC. In contrast, emotional reactivity evaluated in a plus-maze is altered only in the 1W group. No behavioral alterations are observed in mice still drinking alcohol. To determine the causal role of corticosterone in the withdrawal-associated long-lasting WM deficits, we further show that a single intraperitoneal injection injection of metyrapone (an inhibitor of corticosterone synthesis) 30 minutes before testing, prevents withdrawal-associated WM deficits and reestablishes PFC activity, as assessed by increased phosphorylated C-AMP Response Element-binding protein (CREB) immunoreactivity in withdrawn mice. Finally, we show that intra-PFC blockade of mineralocorticoid receptors by infusion of spironolactone and, to a lesser extent, of GCs receptors by injection of mifepristone reverses the WM deficits induced by withdrawal whereas the same injections into the dHPC do not. Overall, our study evidences that long-lasting GCs dysfunction selectively in the PFC is responsible for the emergence and maintenance of WM impairments after withdrawal and that blocking prefrontal mineralocorticoid receptors receptors restores WM in withdrawn animals. PMID- 26860617 TI - Health-related quality of life and prospective caries development. AB - BACKGROUND: The present study was conducted to prospectively assess the association between health-related quality of life (HRQoL) and the development of dental caries in adults in northern Sweden. The SF-36 questionnaire was used to estimate HRQoL. METHODS: Adults who had (i) participated in a population-based health screening in northern Sweden between 2003 and 2009 and had completed the SF-36 questionnaire, and (ii) received a dental check-up within 1 year (n = 15,615) were included in the study. Of these, 9,838 had a second caries examination 2-7 years after the baseline recording. Information regarding SF-36, lifestyle factors and medical conditions was retrieved by questionnaires, and anthropometric status and blood lipid levels were measured. The association between dental caries (outcome) and SF-36 scores (exposure) with the inclusion of potential confounders was analysed by linear and logistic regression. RESULTS: Caries increment increased significantly with decreasing scores for both physical and mental dimensions of SF-36 in women, but no association was seen in men. However, lifelong caries experience (DMFS) increased linearly with decreasing physical HRQoL in both men and women; this was also observed for the single dimension of mental HRQoL. The crude odds ratio for being in the highest caries quintile compared to the lowest when having the poorest physical HRQoL compared with the best physical HRQoL was 1.88 (95 % CI: 1.54-2.3). Several factors were identified as potential confounders in the associations between DMFS and SF-36 scores, including education level, smoking, age, medications, higher levels of total cholesterol, triglycerides, systolic blood pressure, body mass index and sugar intake. Except for education level and smoking, the effect sizes for the association between gradually decreasing SF-36 scores and increasing caries were generally moderate. CONCLUSIONS: Increased development of caries was associated with low physical HRQoL and some aspects of mental HRQoL. The mechanisms underlying these associations, which are likely confounded by both biological and lifestyle factors, remain to be elucidated. The study implies that, when possible, subjects with poor HRQoL would benefit from caries prevention measures meeting the underlying situation. PMID- 26860615 TI - A network-based analysis of colon cancer splicing changes reveals a tumorigenesis favoring regulatory pathway emanating from ELK1. AB - Splicing aberrations are prominent drivers of cancer, yet the regulatory pathways controlling them are mostly unknown. Here we develop a method that integrates physical interaction, gene expression, and alternative splicing data to construct the largest map of transcriptomic and proteomic interactions leading to cancerous splicing aberrations defined to date, and identify driver pathways therein. We apply our method to colon adenocarcinoma and non-small-cell lung carcinoma. By focusing on colon cancer, we reveal a novel tumor-favoring regulatory pathway involving the induction of the transcription factor MYC by the transcription factor ELK1, as well as the subsequent induction of the alternative splicing factor PTBP1 by both. We show that PTBP1 promotes specific RAC1,NUMB, and PKM splicing isoforms that are major triggers of colon tumorigenesis. By testing the pathway's activity in patient tumor samples, we find ELK1,MYC, and PTBP1 to be overexpressed in conjunction with oncogenic KRAS mutations, and show that these mutations increase ELK1 levels via the RAS-MAPK pathway. We thus illuminate, for the first time, a full regulatory pathway connecting prevalent cancerous mutations to functional tumor-inducing splicing aberrations. Our results demonstrate our method is applicable to different cancers to reveal regulatory pathways promoting splicing aberrations. PMID- 26860619 TI - AMHB: (Anti)aromaticity-Modulated Hydrogen Bonding. AB - This in silico survey shows that changes in the (anti)aromatic character of pi conjugated heterocycles can be used to fine-tune their hydrogen (H-)bond strengths. Upon H-bonding dimerization, the pi-electrons of these rings can be polarized to reinforce or disrupt their (anti)aromatic pi-conjugated circuits (piCCs) and stabilize or destabilize the resulting H-bonded complexes. H-bonding interactions that enhance aromaticity or relieve antiaromaticity are fortified, whereas those that intensify antiaromaticity or disrupt aromaticity are weakened, relative to analogues lacking full pi-circuits. Computed dissected nucleus independent chemical shifts, NICS(1)(zz), reveal a uniform pattern and document changes in the magnetic (anti)aromatic character of the heterocycles considered. Recognition of this (anti)aromaticity-modulated H-bonding (AMHB) phenomenon offers insights into a range of fields from organocatalysis and self-assembly to pharmaceutical chemistry and molecular biology. PMID- 26860618 TI - Effect of hydraulic retention time and sludge recirculation on greenhouse gas emission and related microbial communities in two-stage membrane bioreactor treating solid waste leachate. AB - Methane (CH4) and nitrous oxide (N2O) emissions and responsible microorganisms during the treatment of municipal solid waste leachate in two-stage membrane bioreactor (MBR) was investigated. The MBR system, consisting of anaerobic and aerobic stages, were operated at hydraulic retention time (HRT) of 5 and 2.5days in each reactor under the presence and absence of sludge recirculation. Organic and nitrogen removals were more than 80% under all operating conditions during which CH4 emission were found highest under no sludge recirculation condition at HRT of 5days. An increase in hydraulic loading resulted in a reduction in CH4 emission from anaerobic reactor but an increase from the aerobic reactor. N2O emission rates were found relatively constant from anaerobic and aerobic reactors under different operating conditions. Diversity of CH4 and N2O producing microorganisms were found decreasing when hydraulic loading rate to the reactors was increased. PMID- 26860620 TI - Before-school and after-school childcare and children's risk of obesity. AB - BACKGROUND: In the USA, half of children are regularly cared for before or after school by someone other than a parent. OBJECTIVE: Describe the relationship between childcare arrangements and obesity among school-aged children. METHODS: Data are from the fifth-grade wave of the Early Childhood Longitudinal Study - Kindergarten Cohort 1998-1999, a nationally representative study of US children who were in kindergarten in 1998-1999 or first grade in 1999, collected in spring 2004 (analytic sample = 9617). We estimated survey-adjusted logistic regression models to examine the association between childcare arrangements before and after school and obesity. RESULTS: The prevalence of obesity was highest among fifth graders who received care from multiple sources and lowest among children who received care from adults not related to them in either the child's or the caregiver's home [29.9%, 95% confidence interval {CI}: 18.7%, 44.3%; and 17.3%, 95% CI: 12.1%, 24.0%]. Childcare arrangement was not an independent risk factor for obesity for most children. However, Hispanic children who were cared for by a person who was not a relative had significantly higher odds of obesity compared with non-Hispanics in similar care arrangements (odds ratio: 5.11, 95% CI: 2.00, 13.06). CONCLUSION: Type of childcare before or after school was not an independent risk factor for obesity in most fifth graders, but implications of childcare for Hispanic children should be explored further. PMID- 26860621 TI - Indications for intubation and early tracheostomy in patients with Stevens Johnson Syndrome and Toxic Epidermal Necrolysis. AB - BACKGROUND: Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) result in epidermal sloughing and mucositis. There are no published guidelines for intubation and early tracheostomy in this patient population. METHODS: A retrospective chart review of 40 patients admitted from 2010 to 2015 with SJS and TEN was conducted. Descriptive statistics and significance were calculated. RESULTS: Of the 43% of patients who underwent early tracheostomy, 100% had oral involvement while the initial total body surface area (TBSA) was 70% or more in 41% of patients (P < .05). TBSA progressed 15% or more in 53% of patients with 6% having airway involvement and a neurologic diagnosis mandating intubation. Mortality was 17%. CONCLUSIONS: Indications for intubation and early tracheostomy for SJS and TEN are documented oral involvement plus one of the following: initial TBSA 70% or more; progression of TBSA involved from hospital day 1 to hospital day 3, 15% TBSA or more; underlying neurologic diagnosis preventing airway protection; and documented airway involvement on direct laryngoscopy. PMID- 26860622 TI - Explaining the excess morbidity of emergency general surgery: packed red blood cell and fresh frozen plasma transfusion practices are associated with major complications in nonmassively transfused patients. AB - BACKGROUND: Intraoperative blood product transfusions carry risk but are often necessary in emergency general surgery (EGS). METHODS: We queried the American College of Surgery-National Surgical Quality Improvement Program database for EGS patients (2008 to 2012) at 2 tertiary academic hospitals. Outcomes included rates of high packed red blood cell (pRBC) use (estimated blood loss:pRBC < 350:1) and high fresh frozen plasma (FFP) use (FFP:pRBC >1:1.5). Patients were then stratified by exposure to high blood product use. Stepwise logistic regression was performed. RESULTS: Of 992 patients, 33% underwent EGS. Estimated blood loss was similar between EGS and non-EGS (282 vs 250 cc, P = .288). EGS patients were more often exposed to high pRBC use (adjusted odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.11 to 3.66) and high-FFP use (OR = 2.75, 95% CI: = 1.10 to 6.84). High blood product use was independently associated with major nonbleeding complications (high pRBC: OR = 1.73, 95% CI = 1.04 to 2.91; high FFP: OR = 2.15, 95% CI = 1.15 to 4.02). CONCLUSIONS: Despite similar blood loss, EGS patients received higher rates of intraoperative blood product transfusion, which was independently associated with major complication. PMID- 26860623 TI - Guidelines and Recommendations for Developing Interactive eHealth Apps for Complex Messaging in Health Promotion. AB - BACKGROUND: The now ubiquitous catchphrase, "There's an app for that," rings true owing to the growing number of mobile phone apps. In excess of 97,000 eHealth apps are available in major app stores. Yet the effectiveness of these apps varies greatly. While a minority of apps are developed grounded in theory and in conjunction with health care experts, the vast majority are not. This is concerning given the Hippocratic notion of "do no harm." There is currently no unified formal theory for developing interactive eHealth apps, and development is especially difficult when complex messaging is required, such as in health promotion and prevention. OBJECTIVE: This paper aims to provide insight into the creation of interactive eHealth apps for complex messaging, by leveraging the Safe-D case study, which involved complex messaging required to guide safe but sufficient UV exposure for vitamin D synthesis in users. We aim to create recommendations for developing interactive eHealth apps for complex messages based on the lessons learned during Safe-D app development. METHODS: For this case study we developed an Apple and Android app, both named Safe-D, to safely improve vitamin D status in young women through encouraging safe ultraviolet radiation exposure. The app was developed through participatory action research involving medical and human computer interaction researchers, subject matter expert clinicians, external developers, and target users. The recommendations for development were created from analysis of the development process. RESULTS: By working with clinicians and implementing disparate design examples from the literature, we developed the Safe-D app. From this development process, recommendations for developing interactive eHealth apps for complex messaging were created: (1) involve a multidisciplinary team in the development process, (2) manage complex messages to engage users, and (3) design for interactivity (tailor recommendations, remove barriers to use, design for simplicity). CONCLUSIONS: This research has provided principles for developing interactive eHealth apps for complex messaging as guidelines by aggregating existing design concepts and expanding these concepts and new learnings from our development process. A set of guidelines to develop interactive eHealth apps generally, and specifically those for complex messaging, was previously missing from the literature; this research has contributed these principles. Safe-D delivers complex messaging simply, to aid education, and explicitly, considering user safety. PMID- 26860624 TI - Immune checkpoint therapy for non-small-cell lung cancer: an update. AB - The role of immunotherapy in treatment of non-small-cell lung cancer (NSCLC) has been gaining interest over the past few years. This has been driven primarily by promising results from trials evaluating antagonist antibodies that target co inhibitory immune checkpoints expressed on tumor cells and immune cells within the tumor microenvironment. Immune checkpoints exist to dampen or terminate immune activity to guard against autoimmunity and allow for self-tolerance. However, tumors can take advantage of these immune checkpoint pathways to evade destruction. Antibodies that block inhibitory checkpoints, such as anti-CTLA-4, anti-PD1 and anti-PD-L1 antibodies have demonstrated delayed tumor growth and increased survival. Novel therapies are now investigating combining checkpoint inhibitors with chemotherapy, targeted therapy, radiation and vaccines to produce synergistic antitumor activity. PMID- 26860625 TI - Balancing cultural pluralism and universal bioethical standards: a multiple strategy. AB - If we want to take firm the importance of universal principles in Bioethics, but at the same time we want to take seriously the importance of cultural diversity and pluralism, it is necessary to adopt a multifaceted approach. In the article I argue that a possible way out is a sort of hermeneutic approach, in order to reduce the ambivalence that stems from the dual recognition of cultural diversity and universal value of human rights. Through this approach conflicting principles and traditions can be harmonized within a common framework, at least to some extent. Such an approach, in my perspective, can be implemented as a strategy of interpretation, which can hold together different conceptions and common principles. PMID- 26860626 TI - The utility of standardized advance directives: the general practitioners' perspective. AB - Advance directives (AD) are written documents that give patients the opportunity to communicate their preferences regarding treatments they do or do not want to receive in case they become unable to make decisions. Commonly used pre-printed forms have different formats. Some offer space for patients to (a) appoint a surrogate decision maker, and/or (b) to determine future medical treatments and/or (c) give a statement of personal values. So far it is unknown which forms GPs preferably use and why they decide to do so. 23 semi-structured interviews with GPs were analysed using content analysis. Interviewees mainly use short templates (to appoint surrogate decision makers) and medium length templates with checkboxes to indicate patients' preferences in regards to life prolonging measures. Especially when patients faced the progression of a disease, participants use the latter version. Only then, the interviewees remarked, patients are capable to rate concrete situations reliably. GPs also realize the importance of the verbal assessment of patients' preferences; however they rarely keep a written form of the conversation. Some GPs hand out one or more templates and ask their patients to read and think about them at home with the option to talk to them about it later on, while others prefer their patients to fill them out alone at home. Regardless of template usage, most GPs emphasize that ADs require regular updates. GPs tend to see standardized advance directives mainly as a tool to start a conversation with their patients and to identify their real preferences and values. When the patient is still not facing the progression of an already existing disease it could be sufficient to only appoint a surrogate decision maker instead of creating a full AD. However, in all other situations, appointing a surrogate decision maker should be backed up by a written statement of a patient's general values. Patients and their relatives should always have the opportunity to ask their GP for medical advice when drafting an AD. It is crucial to regularly verify and update existing ADs within the course of a disease. PMID- 26860628 TI - Genetic and geographical structure of boreal plants in their southern range: phylogeography of Hippuris vulgaris in China. AB - BACKGROUND: Our current understanding of the evolutionary history of boreal and arctic-alpine plants in their southern range in Asia remains relatively poor. Using three cpDNA non-coding regions and nine nuclear microsatellite (nSSR) loci, we examine the phylogeographic pattern in a broad geographic sampling of the boreal plant Hippuris vulgaris to infer its dispersal and diversification in China. In addition, the species distributions at the Last Glacial Maximum (LGM) and at present were predicted using ecological niche modeling (ENM). RESULTS: The cpDNA results revealed two distinct lineages, A and B. A is restricted to Northeast China; B is distributed in Northwest China, the Qinghai-Tibet Plateau (QTP) and North and Northeast (NNE) China; and A and B diverged ca. 1.36 Ma. The nSSR data revealed two genetic clusters corresponding to the two cpDNA lineages and nonreciprocal hybridization with lineage A as the maternal lineage in Northeast China. Cluster B further divided into three subclusters: I, mainly in NNE China and the northeastern border of the QTP; II, in Northwest China and the QTP; and III, on the QTP. ENM predicted a marked range shift on the QTP at the LGM, retreating from the platform to the northeast and southeast edges. CONCLUSIONS: Hippuris vulgaris probably diverged into lineages A and B in high latitudes and then immigrated into Northeast China and Northwest China, respectively. Lineage A persisted and diversified in Northeast China. Lineage B reached the QTP during the mid-Pleistocene, diversified in that region due to the influence of climatic oscillations, migrated into Northeast China and subsequently hybridized with lineage A. Our findings give empirical evidence that boreal plants display complex evolutionary history in their southern range in Asia and provide new insights into the evolution of boreal and arctic-alpine plants. PMID- 26860627 TI - Advancing Product Quality: a Summary of the Second FDA/PQRI Conference. PMID- 26860629 TI - Trachoma. AB - INTRODUCTION: Active trachoma is caused by chronic infection of the conjunctiva by Chlamydia trachomatis, and is the world's leading infectious cause of blindness. Infection can lead to: scarring of the tarsal conjunctiva; inversion of the eyelashes (trichiasis), so that they abrade the cornea; and corneal opacity, resulting in blindness. Trachoma is a disease of poverty, overcrowding, and poor sanitation. Active disease affects mainly children, but adults are at increased risk of scarring. METHODS AND OUTCOMES: We conducted a systematic overview, aiming to answer the following clinical question: What are the effects of interventions to prevent scarring trachoma by reducing the prevalence of active trachoma? We searched: Medline, Embase, The Cochrane Library and other important databases up to December 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). RESULTS: At this update, searching of electronic databases retrieved 170 studies. After deduplication and removal of conference abstracts, 96 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 61 studies and the further review of 35 full publications. Of the 35 full articles evaluated, three previously included systematic reviews were updated, one systematic review and two RCTs were added at this update, and two RCTs and one further report were added the Comment sections. We performed a GRADE evaluation for nine PICO combinations. CONCLUSIONS: In this systematic overview, we categorised the efficacy for seven interventions based on information about the effectiveness and safety of antibiotics, face washing (alone or plus topical tetracycline), fly control (through the provision of pit latrines, and using insecticide alone or plus antibiotics), and health education. PMID- 26860630 TI - Sexual Debut and HIV-Related Sexual Risk-Taking by Birth Cohort Among Men Who Have Sex with Men in the United States. AB - Age-discordant and earlier sexual debut are risk factors for HIV among men who have sex with men (MSM). Despite differences in the sociopolitical landscape over time, there are no studies sampling participants from the United States that have examined the role of birth cohort in relations between sexual debut characteristics and sexual risk among MSM. We assessed sexual debut patterns and associations with sexual risk-taking in 812 adult MSM stratified by ten-year birth cohorts (i.e., before 1970, 1970-1979, 1980-1989, after 1990). Sexual debut characteristics differed by birth cohort. In multivariate models controlling for birth cohort, both younger age of sexual debut and younger age of anal sex debut were associated with an increased likelihood of condomless sex. Men born in the 1990s had increased odds of engaging in sexual risk regardless of sexual debut characteristics. Sexual risk reduction interventions tailored to the unique needs of young MSM are encouraged. PMID- 26860631 TI - Collective action for implementation: a realist evaluation of organisational collaboration in healthcare. AB - BACKGROUND: Increasingly, it is being suggested that translational gaps might be eradicated or narrowed by bringing research users and producers closer together, a theory that is largely untested. This paper reports a national study to fill a gap in the evidence about the conditions, processes and outcomes related to collaboration and implementation. METHODS: A longitudinal realist evaluation using multiple qualitative methods case studies was conducted with three Collaborations for Leadership in Applied Health Research in Care (England). Data were collected over four rounds of theory development, refinement and testing. Over 200 participants were involved in semi-structured interviews, non participant observations of events and meetings, and stakeholder engagement. A combined inductive and deductive data analysis process was focused on proposition refinement and testing iteratively over data collection rounds. RESULTS: The quality of existing relationships between higher education and local health service, and views about whether implementation was a collaborative act, created a path dependency. Where implementation was perceived to be removed from service and there was a lack of organisational connections, this resulted in a focus on knowledge production and transfer, rather than co-production. The collaborations' architectures were counterproductive because they did not facilitate connectivity and had emphasised professional and epistemic boundaries. More distributed leadership was associated with greater potential for engagement. The creation of boundary spanning roles was the most visible investment in implementation, and credible individuals in these roles resulted in cross-boundary work, in facilitation and in direct impacts. The academic-practice divide played out strongly as a context for motivation to engage, in that 'what's in it for me' resulted in variable levels of engagement along a co-operation-collaboration continuum. Learning within and across collaborations was patchy depending on attention to evaluation. CONCLUSIONS: These collaborations did not emerge from a vacuum, and they needed time to learn and develop. Their life cycle started with their position on collaboration, knowledge and implementation. More impactful attempts at collective action in implementation might be determined by the deliberate alignment of a number of features, including foundational relationships, vision, values, structures and processes and views about the nature of the collaboration and implementation. PMID- 26860633 TI - Novel learning accelerates systems consolidation of a contextual fear memory. AB - After initial encoding memories may undergo a time-dependent reorganization, becoming progressively independent from the hippocampus (HPC) and dependent on cortical regions such as the anterior cingulate cortex (ACC). Although the mechanisms underlying systems consolidation are somewhat known, the factors determining its temporal dynamics are still poorly understood. Here, we studied the influence of novel learning occurring between training and test sessions on the time-course of HPC- and ACC-dependency of contextual fear conditioning (CFC) memory expression. We found that muscimol was disruptive when infused into the HPC up to 35 days after training, while the ACC is vulnerable only after 45 days. However, when animals were subjected to a series of additional, distinct tasks to be learned within the first 3 weeks, muscimol became effective sooner. Muscimol had no effect in the HPC at 20 days after training, exactly when the ACC becomes responsive to this treatment. Thus, our data indicates that the encoding of new information generates a tight interplay between distinct memories, accelerating the reorganization of previously stored long term memories between the hippocampal and cortical areas. (c) 2016 Wiley Periodicals, Inc. PMID- 26860632 TI - A Phase II trial of tandutinib (MLN 518) in combination with bevacizumab for patients with recurrent glioblastoma. AB - AIM: A Phase II trial of bevacizumab plus tandutinib. METHODS: We enrolled 41 recurrent, bevacizumab-naive glioblastoma patients for a trial of bevacizumab plus tandutinib. Median age was 55 and 71% were male. Treatment consisted of tandutinib 500 mg two-times a day (b.i.d.) and bevacizumab 10 mg/kg every 2 weeks starting day 15. Of 37 (90%) evaluable, nine (24%) had partial response. RESULTS & CONCLUSION: Median overall and progression-free survival was 11 and 4.1 months; progression-free survival at 6 months was 23%. All patients suffered treatment related toxicities; common grade >=3 toxicities were hypertension (17.1%), muscle weakness (17.1%), lymphopenia (14.6%) and hypophosphatemia (9.8%). Four of six with grade >=3 tandutinib-related myasthenic-like muscle weakness had electromyography-proven neuromuscular junction pathology. Tandutinib with bevacizumab was as effective but more toxic than bevacizumab monotherapy. PMID- 26860634 TI - Alternative-Donor Hematopoietic Stem Cell Transplantation with Post Transplantation Cyclophosphamide for Nonmalignant Disorders. AB - Allogeneic hematopoietic stem cell transplantation (HSCT) is curative for many nonmalignant pediatric disorders, including hemoglobinopathies, bone marrow failure syndromes, and immunodeficiencies. There is great success using HLA matched related donors for these patients; however, the use of alternative donors has been associated with increased graft failure, graft-versus-host disease (GVHD), and transplant-related mortality (TRM). HSCT using alternative donors with post-transplantation cyclophosphamide (PT/Cy) for GVHD prophylaxis has been performed for hematologic malignancies with engraftment, GVHD, and TRM comparable with that seen with HLA-matched related donors. There are limited reports of HSCT in nonmalignant pediatric disorders other than hemoglobinopathies using alternative donors and PT/Cy. We transplanted 11 pediatric patients with life threatening nonmalignant conditions using reduced-intensity conditioning, alternative donors, and PT/Cy alone or in combination with tacrolimus and mycophenolate mofetil. We observed limited GVHD, no TRM, and successful engraftment sufficient to eliminate manifestations of disease in all patients. Allogeneic HSCT using alternative donors and PT/Cy shows promise for curing nonmalignant disorders; development of prospective clinical trials to confirm these observations is warranted. PMID- 26860636 TI - Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study. AB - Post-transplant high-dose cyclophosphamide (PTCy) is a novel approach to prevent graft-versus-host disease (GVHD) and rejection in patients given haploidentical hematopoietic stem cell transplantation (HSCT). Thirty-three patients with high risk hematologic malignancies and lacking a match-related or -unrelated donor were treated with PTCy haploidentical HSCT in 5 Italian AIEOP centers. Nineteen patients had a nonmyeloablative preparative regimen (57%), and 14 patients received a full myeloablative conditioning regimen (43%). No patients received serotherapy; GVHD prophylaxis was based on PTCy (50 mg/kg on days +3 and +4) combined with mycophenolate plus tacrolimus or cyclosporine A. Neutrophil and platelet engraftment was achieved on days +17 (range, 14 to 37) and +27 (range, 16 to 71). One patient had autologous reconstitution for anti-HLA antibodies. Acute GVHD grades II to IV and III to IV and chronic GVHD developed in 22% (95% CI, 11 to 42), 3% (95% CI, 0 to 21), and 4% (95% CI, 0 to 27) of cases, respectively. The 1-year overall survival rate was 72% (95% CI, 56 to 88), progression-free survival rate was 61% (95% CI, 43 to 80), cumulative incidence of relapse was 24% (95% CI, 13 to 44), and transplant-related mortality was 9% (95% CI, 3 to 26). The univariate analysis for risk of relapse incidence showed how 3 significant variables, mother as donor (P = .02), donor gender as female (P = .04), and patient gender as female (P = .02), were significantly associated with a lower risk of relapse. Disease progression was the main cause of death. PTCy is a safe procedure also for children and adolescents who have already received several lines of chemotherapy. Among the different diseases, a trend for better 1-year rates of overall survival was obtained for nonacute leukemia patients. PMID- 26860635 TI - Addition of 10-Day Decitabine to Fludarabine/Total Body Irradiation Conditioning is Feasible and Induces Tumor-Associated Antigen-Specific T Cell Responses. AB - Allogeneic hematopoietic cell transplantation (HCT) offers the possibility of curative therapy for patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myelogenous leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics and in patients who cannot tolerate consolidation chemotherapy (eg, due to previous toxicity). We assessed the toxicity and efficacy of 10-day decitabine (Dec), fludarabine (Flu), and 2 Gy total body irradiation (TBI) as a new conditioning regimen for allogeneic HCT in patients with MDS, CMML, or AML. Thirty patients were enrolled, including 11 with MDS, 2 with CMML, and 17 with AML. Patients received 20 mg/m(2)/day Dec on days -11 to -2, 30 mg/m(2)/day Flu on days -4 to -2, and 2 Gy TBI on day -1, followed by infusion of a donor stem cell graft on day 0. Postgrafting immunosuppression consisted of cyclosporin A and mycophenolate mofetil. At a median follow-up of 443 days, the overall survival was 53%, relapse incidence was 27%, and nonrelapse mortality was 27%. The incidence of severe acute (grade III/IV) graft-versus-host disease (GVHD) was 27%, and that of (predominantly mild) chronic GVHD was 60%. Immunomonitoring studies revealed that specific CD8(+) T cell responses against epigenetically silenced tumor-associated antigens (TAAs), including cancer-testis antigens (MAGE A1/A2/A3 and PRAME) and RHAMM, occurred more frequently in patients who had received Dec/Flu/TBI conditioning (8 of 11 patients) compared with a control group of patients who had received only Flu/TBI conditioning (2 of 9 patients). In summary, Dec/Flu/TBI conditioning proved feasible and effective and enhanced the induction of TAA-reactive CD8(+) T cell responses in vivo, which may contribute to disease control post-transplantation. PMID- 26860638 TI - Annotated checklist of the living sharks, batoids and chimaeras (Chondrichthyes) of the world, with a focus on biogeographical diversity. AB - An annotated checklist of the chondrichthyan fishes (sharks, batoids and chimaeras) of the world is presented. As of 7 November 2015, the number of species totals 1188, comprising 16 orders, 61 families and 199 genera. The checklist includes nine orders, 34 families, 105 genera and 509 species of sharks; six orders, 24 families, 88 genera and 630 species of batoids (skates and rays); one order, three families, six genera and 49 species of holocephalans (chimaeras). The most speciose shark orders are the Carcharhiniformes with 284 species, followed by the Squaliformes with 119. The most species-rich batoid orders are the Rajiformes with 285 species and the Myliobatiformes with 210. This checklist represents the first global checklist of chondrichthyans to include information on maximum size, geographic and depth distributions, as well as comments on taxonomically problematic species and recent and regularly overlooked synonymizations. Furthermore, a detailed analysis of the biogeographical diversity of the species across 10 major areas of occurrence is given, including updated figures for previously published hotspots of chondrichthyan biodiversity, providing the detailed numbers of chondrichthyan species per major area, and revealing centres of distribution for several taxa. PMID- 26860637 TI - Second Cancer Risk and Late Mortality in Adult Australians Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Population-Based Cohort Study. AB - We quantified the risk of second cancer and late mortality in a population-based Australian cohort of 3273 adult (>=15 years) allogeneic hematopoietic stem cell transplant recipients (1992 to 2007). Most recipients received nonradiation-based conditioning and a peripheral blood graft from a matched related donor. Using record linkage with death and cancer registries, 79 second cancers were identified a median of 3.5 years after transplantation. The competing-risk adjusted cumulative incidence of second cancers was 3.35% (95% CI, 2.59 to 4.24) at 10 years, and the cancer risk relative to the matched general population was 2.10 (95% CI, 1.65 to 2.56). We observed an excess risk of melanoma and lip, tongue, esophagus, and soft tissue cancers. Cancer risk relative to the general population was elevated for those transplanted for lymphoma, some leukemia subtypes, and severe aplastic anemia, recipients who developed chronic graft versus-host disease (cGVHD) and irrespective of radiation-based conditioning or stem cell source. In those alive 2 years after transplantation (n = 1463), the cumulative incidence of late mortality was 22.2% (95% CI, 19.7 to 24.9) at 10 years, and the risk of death relative to the matched general population was 13.8 (95% CI, 12.2 to 15.6). In multivariable modeling, risk of late death was reduced for females compared with males and those transplanted for chronic myeloid leukemia compared with acute myeloid leukemia; risk was increased for recipients with discordant sex donors, cGVHD, those undergoing second transplants, and disease relapse. Adults undergoing allogeneic transplantation have unique cancer and mortality risk profiles that continue to warrant prevention and surveillance activities targeted at high-risk subgroups. PMID- 26860640 TI - A gene encoding a potential adenosine 5'-phosphosulphate kinase is necessary for timely development of Myxococcus xanthus. AB - A Myxococcus xanthus gene, MXAN3487, was identified by transposon mutagenesis to be required for the expression of mcuABC, an operon coding for part of the chaperone-usher (CU) system in this bacterium. The MXAN3487 protein displays sequence and structural homology to adenosine 5'-phosphosulphate (APS) kinase family members and contains putative motifs for ATP and APS binding. Although the MXAN3487 locus is not linked to other sulphate assimilation genes, its protein product may have APS kinase activity in vivo and the importance of the ATP binding site for activity was demonstrated. Expression of MXAN3487 was not affected by sulphate availability, suggesting that MXAN3487 may not function in a reductive sulphate assimilation pathway. Deletion of MXAN3487 significantly delayed fruiting body formation and the production of McuA, a spore coat protein secreted by the M. xanthus Mcu CU system. Based on these observations and data from our previous studies, we propose that MXAN3487 may phosphorylate molecules structurally related to APS, generating metabolites necessary for M. xanthus development, and that MXAN3487 exerts a positive effect on the mcuABC operon whose expression is morphogenesis dependent. PMID- 26860639 TI - Novel Human Three-Domain Antibody Fragments Against sTNFalpha as Well as tmTNFalpha with High Affinity Generated by the Combination of Ribosome Display and E. coli Expression System. AB - Human tumour necrosis factor alpha (hTNFalpha) has been proved to be a validated therapeutic target in a number of immune-mediated inflammatory diseases (IMIDs). Fully human monoclonal antibodies (mAbs) that can neutralize soluble hTNFalpha (sTNFalpha) as well as transmembrane hTNFalpha (tmTNFalpha) are more desirable hTNFalpha antagonists. Here, we report that novel anti-hTNFalpha human low molecular-weight MAbs have been selected and identified using both sTNFalpha and tmTNFalpha as target antigens by the combination of ribosome display and E. coli expression system for the first time. As a newly born engineering small molecular antibody, three-domain antibody fragment (VH /kappa) provides an alternative promising molecular principle to generate biological agents for TNFalpha dependent IMIDs. In this study, a panel of novel human VH /kappas (F09, F21, F49 and F409) with high affinity (10(-10) -10(-9) mol/l) to neutralize sTNFalpha as well as tmTNFalpha was generated by the combination of ribosome display and E. coli expression system. Among the four clones, F21 and F409 could reduce cytotoxicity on L929 cells induced by sTNFalpha as well as tmTNFalpha effectively, and both of them had great potential to inhibit hTNFalpha-mediated NF-kappaB activation. Soluble F21 and F409 were also able to inhibit the binding of hTNFalpha to TNFR1 and TNFR2. The new human antibodies described here have desirable capability to neutralize sTNFalpha as well as tmTNFalpha effectively with high affinity and reasonable stability; this may provide an alternative approach for patients who are not responding adequately to currently available anti-TNFalpha agents. PMID- 26860642 TI - An analysis of IN.PACT DEEP randomized trial on the limitations of the societal guidelines-recommended hemodynamic parameters to diagnose critical limb ischemia. AB - OBJECTIVE: Recent small single-center data indicate that the current hemodynamic parameters used to diagnose critical limb ischemia are insensitive. We investigated the validity of the societal guidelines-recommended hemodynamic parameters against core laboratory-adjudicated angiographic data from the multicenter IN.PACT DEEP (RandomIzed AmPhirion DEEP DEB vs StAndard PTA for the treatment of below the knee Critical limb ischemia) Trial. METHODS: Of the 358 patients in the IN.PACT DEEP Trial to assess drug-eluting balloon vs standard balloon angioplasty for infrapopliteal disease, 237 had isolated infrapopliteal disease with an available ankle-brachial index (ABI), and only 40 of the latter had available toe pressure measurements. The associations between ABI, ankle pressure, and toe pressure with tibial runoff, Rutherford category, and plantar arch were examined according to the cutoff points recommended by the societal guidelines. Abnormal tibial runoff was defined as severely stenotic (>=70%) or occluded and scored as one-, two-, or three-vessel disease. A stenotic or occluded plantar arch was considered abnormal. RESULTS: Only 14 of 237 patients (6%) had an ABI <0.4. Abnormal ankle pressure, defined as <50 mm Hg if Rutherford category 4 and <70 mm Hg if Rutherford category 5 or 6, was found only in 37 patients (16%). Abnormal toe pressure, defined as <30 mm Hg if Rutherford category 4 and <50 mm Hg if Rutherford category 5 or 6, was found in 24 of 40 patients (60%) with available measurements. Importantly, 29% of these 24 patients had an ABI within normal reference ranges. A univariate multinomial logistic regression found no association between the above hemodynamic parameters and the number of diseased infrapopliteal vessels. However, there was a significant paradoxic association where patients with Rutherford category 6 had higher ABI and ankle pressure than those with Rutherford category 5. Similarly, there was no association between ABI and pedal arch patency. CONCLUSIONS: The current recommended hemodynamic parameters fail to identify a significant portion of patients with lower extremity ulcers and angiographically proven severe disease. Toe pressure has better sensitivity and should be considered in all patients with critical limb ischemia. PMID- 26860641 TI - Predictors of major amputation despite patent bypass grafts. AB - OBJECTIVE: Despite patent vein bypass grafts, some patients with critical limb ischemia (CLI) receive major amputations. We analyzed the predictive factors leading to major amputation in the presence of patent lower extremity bypass (LEB) grafts. METHODS: Data from the Project of Ex-Vivo vein graft Engineering via Transfection III (PREVENT III), a large prospective randomized trial of 1404 patients who underwent LEB with vein graft for CLI, were queried for outcomes. The primary outcome was major amputation with patent (PMA) LEB compared with patients with patent LEB who achieved limb salvage (PLS). The population excluded those who received amputation for occluded grafts. A Cox proportional hazard model identified independent predictors. RESULTS: Of 1404 LEB patients, 162 (11.5%) had major amputation: 89 (6.3%) with patent and 73 (5.2%) with occluded LEB. For PMA, 21 of 89 (23.6%) developed critical stenosis and 11 of 21 (52.4%) were revised. For PLS, 460 of 1242 (37.0%) developed critical stenosis and 351 of 460 (76.3%) were revised. Predictive patient factors included having preoperative gangrene (vs rest pain; hazard ratio [HR], 3.504; 95% confidence interval [CI], 1.533-8.007; P = .0029), diabetes (HR, 1.800; 95% CI, 1.006-3.219; P = .0477), black (vs white) race (HR, 1.779; 95% CI, 1.051-3.011; P = .0321), baseline creatinine clearance <25 mL/min (vs >65 mL/min; HR, 1.759; 95% CI, 1.016-3.048; P = .0439), prior history of coronary artery bypass grafting (HR, 1.702; 95% CI, 1.080-2.683; P = .0221), and lower baseline activity quality of life score (HR, 1.401; 95% CI, 1.105-1.778; P = .0054). Postoperative wound factors included gangrenous changes (HR, 5.830; 95% CI, 1.647-20.635; P = .0063), surgical wound necrosis (HR, 5.319; 95% CI, 1.478-19.146; P = .0105), deep (vs superficial) wound infection (HR, 3.815; 95% CI, 1.220-11.927; P = .0213), and wound healing abnormally (HR, 3.754; 95% CI, 1.061-13.278; P = .0402). Associated postoperative consequences leading to PMA included having recurrent CLI symptoms (HR, 2.915; 95% CI, 1.816-4.681; P < .0001), a severe (vs mild) adverse event (HR, 2.751; 95% CI, 1.391-5.443; P = .0036), fewer percutaneous revisions (HR, 2.425; 95% CI, 1.573-3.740; P < .0001), discharge on low-molecular-weight heparin (HR, 2.087; 95% CI, 1.309-3.326; P = .0020), and decreasing days to critical stenosis/occlusion/revision/amputation (HR, 1.010; 95% CI, 1.007-1.012; P < .0001). CONCLUSIONS: Whereas a patent vein graft is important to all vascular surgeons, additional factors should be considered in trying to attain limb salvage for patients with CLI. These factors include intervening surgically before CLI has progressed to a state of gangrene or limited activity and optimizing nutrition, diabetes control, cardiac conditions, and activity level. Revision offers hope for clinical improvement but may be delayed when there is no graft lesion identified. The absence of a graft lesion to revise may also portend amputation despite a patent graft because of nongraft-related factors such as infection. Finally, the experience of a severe (vs mild) adverse event may also result in limb loss despite a patent graft. Systematic efforts to reduce severe adverse events among patients may also lead to increased limb salvage. PMID- 26860643 TI - Comparison of cellular changes in Cavalier King Charles spaniel and mixed breed dogs with myxomatous mitral valve disease. AB - INTRODUCTION: The aim of this study was to determine if there are differences in cellular changes in Cavalier King Charles spaniel (CKCS) myxomatous mitral valves compared to non-CKCS dogs. ANIMALS: Cavalier King Charles spaniels (n = 6) and age-matched mixed breed (n = 6) with severe myxomatous mitral valve disease (MMVD), and normal mixed breed (n = 4) dogs. MATERIALS AND METHODS: Immunohistochemistry staining and qualitative and quantitative analysis of mitral valves sections, examining for the presence of CD11c and CD45, vimentin, alpha smooth muscle actin (alpha-SMA) and embryonic smooth muscle myosin heavy chain (Smemb), von Willebrand factor and CD31 and Ki-67. RESULTS: Vimentin positive cell numbers were increased in the MMVD dogs and distributed throughout the valve with greatest density close to the endothelium. There were no significant differences in cell marker expression for the two diseased groups, but cell numbers were significantly increased compared to controls for alpha-SMA (CKCS only) and Smemb (CKCS and mixed breed: p < 0.05). Alpha smooth muscle actin+ cells were primarily located at the valve edge, with Smemb+ cells similarly located, but also present throughout the valve stroma. A small number of cells close to the valve edge co-expressed alpha-SMA and Smemb. Endothelial von Willebrand factor expression was identified in all valves, with evidence of disrupted endothelium in the diseased, but was also found in diseased valve stroma. There was no staining for CD11c, CD45 or CD31 in any valve. Ki-67+ cells formed linear clusters at the leaflet tip and were sparsely distributed throughout both myxomatous valve groups. CONCLUSIONS: The cellular changes notes with advanced stage MMVD appear similar for CKCS when compared to mixed breed dogs. PMID- 26860644 TI - Suture materials - Current and emerging trends. AB - Surgical sutures are used to facilitate closure and healing of surgical- or trauma-induced wounds by upholding tissues together to facilitate healing process. There is a wide range of suture materials for medical purpose and the main types include absorbable and nonabsorbable. Recently, there is a growth in the development of classes of suture materials based on their properties and capabilities to improve tissue approximation and wound closure. This review outlines and discusses the current and emerging trends in suture technology including knotless barbed sutures, antimicrobial sutures, bio-active sutures such as drug-eluting and stem cells seeded sutures, and smart sutures including elastic, and electronic sutures. These newer strategies expand the versatility of sutures from being used as just a physical entity approximating opposing tissues to a more biologically active component enabling delivery of drugs and cells to the desired site with immense application potential in both therapeutics and diagnostics. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 1544-1559, 2016. PMID- 26860645 TI - Quantification of dissociation constant in living cells by fluorescence cross correlation spectroscopy. PMID- 26860646 TI - Theoretical and experimental analysis of ototoxic mechanism in the spiral ligament fibrocytes by multi-level simulation with ion transports in the cochlea. PMID- 26860649 TI - Modeling and simulation of pharmacokinetic drug-drug interaction caused by induction of metabolic enzymes. PMID- 26860650 TI - Simulation technology and its application in Systems Biology. PMID- 26860647 TI - Regulation of inorganic phosphate ion homeostasis: crosstalk kidney and other organs. PMID- 26860648 TI - Mechanism analyses and mechanism-based prediction for adverse drug reactions using systems pharmacology. PMID- 26860651 TI - Modified LDL functions in human and LOX-1-mediated signal transductions. PMID- 26860654 TI - Circulating MPs and vascular dysfunction. PMID- 26860653 TI - Angiotensin-converting enzyme 2. PMID- 26860652 TI - Multilevel modeling of physiological systems on PhysioDesigner. PMID- 26860655 TI - High resolution neurography of the brachial plexus by 3 Tesla magnetic resonance imaging. AB - The study of the structures that make up the brachial plexus has benefited particularly from the high resolution images provided by 3T magnetic resonance scanners. The brachial plexus can have mononeuropathies or polyneuropathies. The mononeuropathies include traumatic injuries and trapping, such as occurs in thoracic outlet syndrome due to cervical ribs, prominent transverse apophyses, or tumors. The polyneuropathies include inflammatory processes, in particular chronic inflammatory demyelinating polyneuropathy, Parsonage-Turner syndrome, granulomatous diseases, and radiation neuropathy. Vascular processes affecting the brachial plexus include diabetic polyneuropathy and the vasculitides. This article reviews the anatomy of the brachial plexus and describes the technique for magnetic resonance neurography and the most common pathologic conditions that can affect the brachial plexus. PMID- 26860656 TI - Reproduction, abundance and survivorship of two Alveopora spp. in the mesophotic reefs of Eilat, Red Sea. AB - Although the study of coral reproduction has advanced tremendously over the last few decades, a particular gap exists in our knowledge of the reproductive modes of corals from 'mesophotic coral ecosystems' (MCEs) found at 30-150 m depth. Here, we report for the first time on the reproductive patterns, living cover, and survivorship under different light treatments of two scleractinian species from the MCEs of Eilat, Red-Sea: Alveopora allingi and A. ocellata. Both species are found exclusively within MCEs and are high in both abundance and relative cover. These species display a synchronous gametogenic cycles with consecutive oocyte growth and development. Peak of reproductive activity occurs in late summer (September-October), typified by accelerated oocyte growth, coinciding with the rise in seawater temperature. Estimates of fecundity show mean monthly maxima of 48.5 +/- 26.3 and 23.5 +/- 11.8 (Mean +/- SE) oocytes per cm(2) for A. allingi and A. ocellata respectively, prior to spawning. A comparison of light and temperature regimes in the shallow vs. MCE environments is presented, and the response of these species to changes in these parameters is discussed. A call encouraging the much-needed studies on the sexuality and reproductive modes of MCE coral species is expressed. PMID- 26860657 TI - A modelling approach to explore the critical environmental parameters influencing the growth and establishment of the invasive seaweed Undaria pinnatifida in Europe. AB - A key factor to determine the expansion dynamics and future distribution of non native species is their physiological response to abiotic factors and their changes over time. For this study we developed a spatially explicit, agent-based model of population growth to represent the complex population dynamics of invasive marine macroalgae with heteromorphic biphasic life cycles. The model framework represents this complex life cycle by treating the individual developmental stages (gametophytes/sporophytes) as autonomous agents with unique behaviour/growth parameters. It was parameterised to represent a well-documented invasive algal species, the Asian kelp Undaria pinnatifida, and validated against field results from an in situ population in Brittany, France, showing good quantitative agreement in terms of seasonal changes in abundance/recruitment and growth dynamics. It was then used to explore how local environmental parameters (light availability, temperature and day length) affect the population dynamics of the individual developmental stages and the overall population growth. This type of modelling approach represents a promising tool for understanding the population dynamics of macroalgae from the bottom-up in terms of the individual interactions between the independent life history stages (both microscopic and macroscopic). It can be used to trace back the behaviour of the population as a whole to the underlying physiological and environmental processes impacting each developmental stage and give insights into the roles these play in invasion success. PMID- 26860658 TI - A stochastic spatio-temporal (SST) model to study cell-to-cell variability in HIV 1 infection. AB - Although HIV viremia in infected patients proceeds in a manner that may be accounted for by deterministic mathematical models, single virus-cell encounters following initial HIV exposure result in a variety of outcomes, only one of which results in a productive infection. The development of single molecule tracking techniques in living cells allows studies of intracellular transport of HIV, but it remains less clear what its impact may be on viral integration efficiency. Here, we present a stochastic intracellular mathematical model of HIV replication that incorporates microtubule transport of viral components. Using this model, we could study single round infections and observe how viruses entering cells reach one of three potential fates - degradation of the viral RNA genome, formation of LTR circles, or successful integration and establishment of a provirus. Our model predicts global trafficking properties, such as the probability and the mean time for a HIV viral particle to reach the nuclear pore. Interestingly, our model predicts that trafficking determines neither the probability or time of provirus establishment - instead, they are a function of vRNA degradation and reverse transcription reactions. Thus, our spatio-temporal model provides novel insights into the HIV infection process and may constitute a useful tool for the identification of promising drug targets. PMID- 26860659 TI - On the evolution of patch-type dependent immigration. AB - Empirical studies of dispersal indicate that decisions to immigrate are patch type dependent; yet theoretical models usually ignore this fact. Here, we investigate the evolution of patch-type dependent immigration of a population inhabiting and dispersing in a heterogeneous landscape, which is structured by patches of low and high reward. We model the decision to immigrate in detail from a mechanistic underpinning. With the methods of adaptive dynamics, we derive both analytical and numerical results for the evolution of immigration when life history traits are patch-type dependent. The model exhibits evolutionary branching in a wide parameter range and the subsequent coevolution can lead to a stable coexistence of a generalist, settling in patches of any type, and a specialist that only immigrates into patches of high reward. We find that individuals always settle in the patches of high reward, in which survival until maturation, relative fecundity and emigration probability are high. We investigate how the probability to immigrate into patches of low reward changes with model parameters. For example, we show that immigration into patches of low reward increases when the emigration probability in these patches increases. Further, immigration into patches of low reward decreases when the patches of high reward become less safe during the dispersal season. PMID- 26860660 TI - Rapid mixing of viscous liquids by electrical coiling. AB - The control for the processing of precursor liquids determines whether the properties and functions of the final material product can be engineered. An inherent challenge of processing viscous liquids arises from their large resistance to deform. Here, we report on the discovery of an electric approach that can significantly contribute to address this challenge. The applied electric force can induce a straight viscous jet to coil, and the resulting coiling characteristics are governed by the electric stress. We demonstrate the promising use of electrical coiling in the rapid and efficient mixing of viscous liquids. Remarkably, the degree of mixing can be precisely adjusted by tuning the applied electric stress. Our approach of controlling the coiling electrically has important implications on applications such as dispensing and printing of resins, printing patterned surfaces and scaffolds, processing of food and generating non woven fabrics. PMID- 26860662 TI - MR imaging of healthy knees in varying degrees of flexion using a stretchable coil array provides comparable image quality compared to a standard knee coil array. AB - OBJECTIVE: Stretchable coils allow knee imaging at varying degrees of flexion. Purpose was to compare a new-developed stretchable 8-channel to a standard 8 channel knee coil array by means of quantitative and qualitative image analysis. MATERIAL AND METHODS: IRB approved prospective study. Knee MR imaging in 10 healthy volunteers was performed at 3T using a standard 8-channel and a new developed stretchable 8-channel coil array at 0 degrees , 45 degrees , and 60 degrees of flexion and at 0 degrees (standard coil). Image parameters were identical. Signal-to-noise ratio (SNR) was determined by combining the images with separately acquired noise data on a pixel-by-pixel basis using MATLAB routines (Natick, MA, USA). Images were qualitatively analysed by two independent radiologists who graded the visibility of several anatomic structures from 1=not visible to 5=excellent. ANOVA, Wilcoxon and kappa statistics were used. RESULTS: Mean SNR+/-standarddeviation of bone was 54.7+/-10.4 and of muscle 28.0+/- 4.4 using the stretchable coil array and 54.6+/-8.2 and 33.4+/-4.5, respectively, using the standard knee coil array. No statistically significant SNR differences were found between both arrays (bone, p=0.960; muscle, p=0.132). SNR was not degraded at higher degrees of flexion. The qualitative image analysis did not reveal statistically significant differences between the stretchable and standard coil array with regard to the visibility of anatomic structures (p=0.026-1.000). Overall kappa was 0.714. CONCLUSION: Stretchable 8-channel coil arrays provide similar SNR and visibility of anatomic structures compared to standard 8-channel knee coil arrays. MR imaging with high SNR will now be possible in flexed knees. PMID- 26860661 TI - Using texture analyses of contrast enhanced CT to assess hepatic fibrosis. AB - PURPOSE: To determine the ability of texture analyses of contrast-enhanced CT images for distinguishing between varying degrees of hepatic fibrosis in patients with chronic liver disease using histopathology as the reference standard. MATERIALS AND METHODS: Following IRB approval, 83 patients who underwent contrast enhanced 64-MDCT of the abdomen and pelvis in the portal venous phase between 12/2005 and 01/2013 and who had a liver biopsy within 6 months of the CT were included. An in-house developed, MATLAB-based texture analysis program was employed to extract 41 texture features from each of 5 axial segmented volumes of liver. Using the Ishak fibrosis staging scale, histopathologic grades of hepatic fibrosis were correlated with texture parameters after stratifying patients into three analysis groups, comparing Ishak scales 0-2 with 3-6, 0-3 with 4-6, and 0-4 with 5-6. To assess the utility of texture features, receiver operating characteristic (ROC) curves were constructed and the area under the curve (AUC) was used to determine the performance of each feature in distinguishing between normal/low and higher grades of hepatic fibrosis. RESULTS: A total of 19 different texture features with 7 histogram features, one grey level co occurrence matrix, 6 gray level run length, 1 Laws feature, and 4 gray level gradient matrix demonstrated statistically significant differences for discriminating between fibrosis groupings. The highest AUC values fell in the range of fair performance for distinguishing between different fibrosis groupings. CONCLUSION: These findings suggest that texture-based analyses of contrast-enhanced CT images offer a potential avenue toward the non-invasive assessment of liver fibrosis. PMID- 26860664 TI - Cortical vessel sign on susceptibility weighted imaging reveals clinically relevant hypoperfusion in internal carotid artery stenosis. AB - BACKGROUND AND PURPOSE: Internal carotid artery (ICA) stenosis can lead to cerebral hypoperfusion and is a common cause of stroke. As susceptibility weighted imaging (SWI) has been used for penumbra imaging in acute ischemic stroke, we aimed at analyzing hypoperfusion using SWI in patients with ICA stenosis. MATERIAL AND METHODS: Clinical characteristics, asymmetric cortical vessel sign (more and/or larger, hypointense asymmetric cortical vessels) on SWI, Doppler sonography results and diffusion weighted imaging (DWI) lesion volume were retrospectively analyzed in patients with ICA stenosis. In a subgroup of patients, volume of prolonged time to peak and volume of prolonged time to peak of the residue curve (Tmax) were measured as reference standard. Outcome was assessed as modified Rankin score at discharge. RESULTS: 104 patients were included. Median age was 72 and median degree of stenosis 70% according to NASCET. 13% had a asymmetric cortical vessel sign. These patients had a higher degree of stenosis (80% vs. 70%, p=0.004), were more often symptomatic (93% vs. 61%, p=0.020) and had higher DWI volume (7.3ml vs. 0.2ml, p=0.011). Specificity for the prediction of DWI lesions was 86%. Also, patients with asymmetric cortical vessel sign had lower rates of favorable outcome (mRS=0-2; 57% vs. 82%, p=0.033) and volumes of Tmax>=4s, >=6s, >=8s, >=10s and TTP>=2s, >=4s, >=6s were significantly higher. In multivariate analysis, asymmetric cortical vessel sign was an independent negative predictor of favorable outcome (mRS 0-2; OR 0.184; CI [0.039; 0.875] p=0.033). CONCLUSION: In patients with ICA stenosis, asymmetric cortical vessel sign is a sign of clinically relevant hypoperfusion. PMID- 26860663 TI - Comparison of CT volumetric measurement with RECIST response in patients with lung cancer. AB - PURPOSE: To examine the correlations between uni-dimensional RECIST and volumetric measurements in patients with lung adenocarcinoma and to assess their association with overall survival (OS) and progression-free survival (PFS). MATERIALS AND METHODS: In this study of patients receiving chemotherapy for lung cancer in the setting of a clinical trial, response was prospectively evaluated using RECIST 1.0. Retrospectively, volumetric measurements were recorded and response was assessed by two different volumetric methods at each followup CT scan using a semi-automated segmentation algorithm. We subsequently evaluated the correlation between the uni-dimensional RECIST measurements and the volumetric measurements and performed landmark analyses for OS and PFS at the completion of the first and second follow-ups. Kaplan-Meier curves together with log-rank tests were used to evaluate the association between the different response criteria and patient outcome. RESULTS: Forty-two patients had CT scans at baseline, after the first follow up scan and second followup scan, and then every 8 weeks. The uni dimensional RECIST measurements and volumetric measurements were strongly correlated, with a Spearman correlation coefficient (rho) of 0.853 at baseline, rho=0.861 at the first followup, rho=0.843 at the 2nd followup, and rho=0.887 overall between-subject. On first follow-up CT, partial responders and non responders as assessed by an "ellipsoid" volumetric criteria showed a significant difference in OS (p=0.008, 1-year OS of 70% for partial responders and 46% for non responders). There was no difference between the groups when assessed by RECIST criteria on first follow-up CT (p=0.841, 1-year OS rate of 64% for partial responders and 64% for non responders). CONCLUSION: Volumetric response on first follow-up CT may better predict OS than RECIST response. CLINICAL RELEVANCE STATEMENT: Assessment of tumor size and response is of utmost importance in clinical trials. Volumetric measurements may help to better predict OS than uni dimensional RECIST criteria. PMID- 26860665 TI - Prognostic value of volumetric PET parameters in unresectable and metastatic esophageal cancer. AB - PURPOSE: To assess the prognostic value of volumetric parameters measured with PET/CT in patients with advanced or metastatic esophageal cancer (EC). MATERIALS AND METHODS: We identified 71 patients (33 adenocarcinoma [AC] and 38 squamous cell carcinoma [ESCC]) with unresectable or metastatic EC who had PET/CT prior to palliative treatment. Volumetric parameters (metabolic tumor volume [MTV], total lesion glycolysis [TLG], tumor length [TL]) as well as maximum and mean standardized uptake (SUVmax, SUVmean) were obtained from (18)F-FDG PET/CT studies. The correlation between overall survival (OS) and established clinical parameters was assessed using a Cox proportional hazards model. RESULTS: ESCC patients had higher SUVmax and SUVmean compared to AC (p=0.002 and p<0.001, respectively). There was an association of lower SUVmax and SUVmean with metastatic compared to locally advanced tumors (e.g., median SUVmax stage IV: 14.9, 95% confidence interval [95% CI 4.4-35.5] vs. stage IIIA-C: 23.3 [9.2 40.6], p=0.017). TL, MTV and TLG showed an association to OS for all patients and for the subgroup of AC patients (AC; TL: Hazard ratio [HR] 3.23, [95% CI 1.03 10.11], p=0.044; MTV: HR 3.16, [95% CI 1.08-9.23], p=0.035). There was no correlation between PET parameters and survival in ESCC patients. Clinical nodal status was the only clinical variable associated to OS (HR 2.45 [95% CI 1.26 4.75], p=0.008) in AC patients. In a multivariate analysis, nodal status and MTV remained as independent factors associated to OS (N: HR 9.98, [95% CI 1.28 78.11], p=0.028; MTV: HR 1.02, [95% CI 1.01-1.03], p=0.003). CONCLUSIONS: MTV predicted poor OS in patients with advanced AC. No PET parameters were associated to OS in ESCC patients. PMID- 26860666 TI - MR liver imaging with Gd-EOB-DTPA: The need for different delay times of the hepatobiliary phase in patients with different liver function. AB - PURPOSE: To determine the optimal hepatobiliary delay time after Gd-EOB-DTPA injection for lesion characterization in cirrhosis patients with different liver function. MATERIALS AND METHODS: Ninety consecutive patients with liver cirrhosis who underwent Gd-EOB-DTPA-enhanced MRI for the evaluation of known or suspected focal liver lesions were enrolled in this retrospective study. The patients were divided into Child-Pugh A, B and C groups depending on their liver function through the Child-Pugh classification. Hepatobiliary phase images obtained at 5, 10, 15, and 20min were assessed in each group by the following items: parenchymal enhancement, contrast agent excretion into the bile ducts and ureter, and contrast- and signal-to-noise ratios for lesions. RESULTS: In the Child-Pugh A group, parenchymal enhancement increased significantly from 5min to 15min (P<0.05), and stabilized at 20min (P=0.22). However, there was no significant difference in parenchymal enhancement among all of the hepatobiliary phases in the Child-Pugh B and C groups. The biliary contrast agent excretion was first observed before 20min in all of the patients in the Child-Pugh A group, at 20min in 4 patients (25%) in the Child-Pugh B group, and after 20min in 11 patients (78.6%) in the Child-Pugh C group. The numbers of patients whose urethral contrast agent excretion was first observed at 5min in the Child-Pugh A, B and C groups were 38 (63.3%), 12 (75.0%) and 11 (78.6%), respectively. The CNR of the lesions increased significantly (P<0.05), up to 15min after enhancement without a further increase at 20min in the Child-Pugh A group; however, no significant change was found from 5min to 20min in the Child-Pugh B and C groups. For the SNR of lesions, there was no significant difference at 5, 10, 15 and 20min in all of the groups. CONCLUSIONS: A delay time of 15min for the hepatobiliary phase was sufficient for patients with mild liver dysfunction who were classified as Child Pugh A. Nevertheless, for the patients with moderate or severe liver dysfunction who were classified as Child-Pugh B or C, a delay time longer than 5min is meaningless for lesion characterization. PMID- 26860667 TI - Contrast enhanced pulmonary magnetic resonance angiography for pulmonary embolism: Building a successful program. AB - The performance of contrast enhanced pulmonary magnetic resonance angiography (MRA) for the diagnosis of pulmonary embolism (PE) is an effective non-ionizing alternative to contrast enhanced computed tomography and nuclear medicine ventilation/perfusion scanning. However, the technical success of these exams is very dependent on careful attention to the details of the MRA acquisition protocol and requires reader familiarity with MRI and its artifacts. Most practicing radiologists are very comfortable with the performance and interpretation of computed tomographic angiography (CTA) performed to detect pulmonary embolism but not all are as comfortable with the use of MRA in this setting. The purpose of this review is to provide the general radiologist with the tools necessary to build a successful pulmonary embolism MRA program. This review will cover in detail image acquisition, image interpretation, and some key elements of outreach that help to frame the role of MRA to consulting clinicians and hospital administrators. It is our aim that this resource will help build successful clinical pulmonary embolism MRA programs that are well received by patients and physicians, reduce the burden of medical imaging radiation, and maintain good patient outcomes. PMID- 26860668 TI - Detection and size measurements of pulmonary nodules in ultra-low-dose CT with iterative reconstruction compared to low dose CT. AB - BACKGROUND: In this study, the accuracy of ultra-low-dose computed tomography (CT) with iterative reconstruction (IR) for detection and measurement of pulmonary nodules was evaluated. METHODS: Eighty-four individuals referred for lung cancer screening (mean age: 54.5+/-10.8 years) underwent low-dose computed tomography (LDCT) and ultra-low-dose CT. CT examinations were performed with attenuation-based tube current modulation. Reference tube voltage and current were set to 120kV/25mAs for LDCT and 80kV/4mAs for ultra-low-dose CT. CT images were reconstructed with filtered back projection (FBP) for LDCT, and with FBP and IR for ultra-low-dose CT datasets. A reference standard was established by a consensus panel of 2 different radiologists on LDCT. Volume and diameter of the solid nodules were measured on LDCT with FBP and ultra-low dose CT with FBP and IR. Interobserver and interscan variability were analyzed and compared by the Bland-Altman method. RESULTS: A total of 127 nodules were identified, including 105 solid nodules, 15 part solid nodules, 7 ground glass nodules. On ultra-low dose CT scans, the effective radiation dose was 0.13+/-0.11mSv. A total of 113 (88.9%) and 110 (86.6%) true-positive nodules with FBP versus 117 (92.1%) and 118(92.9%) with IR were detected by two observers, respectively. The volume and size of the 105 solid nodules were measured, with mean volume/diameter of 46.5+/ 46.6 mm(3)/5.1+/-1.6mm. There was no significant difference in nodule volume or diameter measurements between ultra-low-dose CT and LDCT protocols for solid nodules. CONCLUSIONS: Ultra-low-dose CT with iterative reconstruction has high sensitivity for lung nodule detection without significant difference in nodule size and volume measurement compared to LDCT. PMID- 26860669 TI - Using air bronchograms on multi-detector CT to predict the invasiveness of small lung adenocarcinoma. AB - PURPOSE: To investigate the prevalence of multidetector CT (MDCT) air bronchograms and their value in predicting the invasiveness of lung adenocarcinomas. METHODS: MDCT scans of 606 nodules in 582 patients with a lung adenocarcinoma less than 2cm in diameter confirmed by surgery and pathology were reviewed. Air bronchograms were classified into three patterns: type I, bronchus with intact lumen; type II, bronchus with dilated or tortuous lumen; and type III, bronchus with obstructed lumen. RESULTS: Air bronchograms were demonstrated on MDCT in 210 of 606 (34.7%) lung adenocarcinomas with 16.6% (35/211) preinvasive lesions (PL), 30.5% (50/164) minimally invasive adenocarcinoma (MIA), and 54.1% (125/231) invasive adenocarcinoma (IAC) (P=0.000); 18.3% (44/240) pure ground-glass nodules (GGNs), 44.2% (137/310) mixed GGNs, and 51.8% (29/56) solid nodules (P=0.000). Type I was slightly more common in MIA (36/164, 22.0%) than IAC (40/231, 17.3%) and PL (30/211, 14.2%) but without differences among them (P=0.147). Type II (PL: 5/211, 2.4%; MIA: 13/164, 7.9%; IAC: 53/231, 22.9%) and type III (PL: 0/211; MIA: 1/164, 0.6%; IAC: 32/231, 13.9%) were observed more frequently with increasing lung adenocarcinoma invasiveness (both P=0.000). CONCLUSIONS: The prevalence and patterns of air bronchograms on MDCT can predict the invasiveness of small lung adenocarcinomas. PMID- 26860670 TI - The application of paramagnetic contrast-based T2 effect to 3D heavily T2W high resolution MR imaging of the brachial plexus and its branches. AB - OBJECTIVE: To introduce a new 3D magnetic resonance neurography (MRN) method involving a paramagnetic contrast-based T2 effect coupled with an advanced 3D heavily T2W SPACE-STIR high resolution imaging sequence that would enhance the contrast between nervous tissue and surrounding tissues. METHODS: Thirty subjects (average age, 39.6+/-17.0 years; 18 male and 12 female) were enrolled, including three patients with brachial plexopathy and 27 healthy volunteers. Subjective scores from two neuroradiologists, evaluating noncontrast MRN (cMRN) and 3D SPACE STIR contrast enhanced MRN (ceMRN) 3D data using a 3-point scoring system, were compared using Wilcoxon signed-rank test. Contrast-to-noise ratios (CNRs), SNRs, and contrast ratios within the brachial plexus on cMRN vs. ceMRN MIP and source images were also compared using the paired t-test. RESULTS: The average score for cMRN (0.77+/-0.43) was significantly lower than ceMRN (1.73+/-0.45) (p<0.001). Lower nerve vs. vein CNRs were found on cMRN vs. ceMRN, respectively (p<0.001 for both source and MIP images). All nerve-to-surrounding tissue contrast ratios (i.e., fat, muscle, veins, and bone) were higher for ceMRN compared with cMRN for both source and MIP images (all p<0.05). CONCLUSION: The improved 3D visualization of the brachial plexus and its branches, using this new contrast enhanced MRN method, can provide high resolution imaging which may be of significant value in the assessment of brachial plexopathy. PMID- 26860671 TI - Prediction of long-term major events soon after a first ST-segment elevation myocardial infarction by cardiovascular magnetic resonance. AB - BACKGROUND: Cardiovascular magnetic resonance (CMR) predicts combined clinical events in post-ST-segment elevation myocardial infarction (STEMI) patients. However, its contribution to predicting long-term major events (ME: cardiac death and non-fatal myocardial infarction [MI]) is unknown. We aimed to assess whether CMR predicts long-term MEs when performed soon after STEMI. METHODS AND RESULTS: We prospectively recruited 546 STEMI patients between 2004 and 2012. The Left ventricular (LV) ejection fraction (LVEF,%), infarct size (IS), edema, hemorrhage, microvascular obstruction, and myocardial salvage were quantified by CMR at pre-discharge. During a mean follow-up of 840 days, 57 ME events (10%; 23 cardiac deaths, 34 non-fatal MIs) were documented. Patients with MEs has more depressed LVEFs (p<0.001), larger ISs (p<0.001), more extensive edema, hemorrhage, and microvascular obstruction, and lower myocardial salvage (p<0.05). CMR indexes were dichotomized according to the best cutoff values for predicting ME. In a comprehensive multivariate model, a LVEF<40% (HR: 2.3; 95% CI [12, 43]; p= 0.009) and an IS>30% of LV mass (HR: 2.4; 95% CI [13, 44]; p= 0.007) independently doubled the ME risk. The ME risk rates were 6%, 14%, and 30%, respectively (p<0.001) in patients with both the LVEF>=40% and an IS<=30% of LV mass (n=393), those with only one altered value (n=84), and in cases with both the LVEF<40% and an IS>30% of LV mass (n=69). Similar tendencies were observed regarding cardiac deaths (2%, 6%, 14%; p<0.001) and MI (4%, 8%, 16%; p < 0.001). CONCLUSIONS: CMR performed soon after STEMI predicts long-term MEs. Combined analysis of CMR-derived LVEF and IS allows robust stratification of patient outcomes. PMID- 26860672 TI - FDG-PET/CT as a post-treatment restaging tool in urothelial carcinoma: Comparison with contrast-enhanced CT. AB - PURPOSE: To assess the clinical usefulness of FDG-PET/CT in the diagnosis of recurrent and metastatic urothelial carcinoma in comparison with contrast enhanced CT. MATERIALS AND METHODS: Eighty-three patients who had undergone treatment for histopathologically proven urothelial carcinoma underwent whole body FDG-PET/CT and contrast-enhanced CT for suspected recurrence within a time interval of two weeks. Patient-based analysis and lesion sites besides the urinary tract, as interpreted by two experienced readers, were compared between the two modalities using McNemar test. Lesion status was determined on the basis of histopathology, radiological imaging and clinical follow-up for longer than 6 months. RESULT: Patient-based analysis showed that the sensitivity, specificity, and accuracy of FDG-PET/CT were 97.4%, 93.3% and 95.2%, respectively, whereas those of contrast-enhanced CT were 86.8%, 93.3% and 90.4%, respectively. The sensitivity and accuracy of FDG-PET/CT were higher than contrast-enhanced CT without significant difference (p=0.13). The sensitivity of FDG-PET/CT for diagnosis of bone metastasis was significantly higher than that of contrast enhanced CT (93.8% vs. 25%, p=0.0026). CONCLUSION: FDG-PET/CT is a more accurate modality than CT for assessment of recurrence outside the urinary tract in patients with urothelial carcinoma, especially for bone lesion. Cystoscopy, urine cytology, and FDG-PET/CT are complementary procedures and may have a definite management role. PMID- 26860673 TI - High-resolution CT with new model-based iterative reconstruction with resolution preference algorithm in evaluations of lung nodules: Comparison with conventional model-based iterative reconstruction and adaptive statistical iterative reconstruction. AB - OBJECTIVE: To compare the image quality of high-resolution computed tomography (HRCT) for evaluating lung nodules reconstructed with the new version of model based iterative reconstruction and spatial resolution preference algorithm (MBIRn) vs. conventional model-based iterative reconstruction (MBIRc) and adaptive statistical iterative reconstruction (ASIR). MATERIALS AND METHODS: This retrospective clinical study was approved by our institutional review board and included 70 lung nodules in 58 patients (mean age, 71.2+/-10.9years; 34 men and 24 women). HRCT of lung nodules were reconstructed using MBIRn, MBIRc and ASIR. Objective image noise was measured by placing the regions of interest on lung parenchyma. Two blinded radiologists performed subjective image analyses. RESULTS: Significant improvements in the following points were observed in MBIRn compared with ASIR (p<0.005): objective image noise (24.4+/-8.0 vs. 37.7+/-10.4), subjective image noise, streak artifacts, and adequateness for evaluating internal characteristics and borders of nodules. The sharpness of small vessels and bronchi and diagnostic acceptability with MBIRn were significantly better than with MBIRc and ASIR (p<0.008). CONCLUSION: HRCT reconstructed with MBIRn provides diagnostically more acceptable images for the detailed analyses of lung nodules compared with MBIRc and ASIR. PMID- 26860674 TI - Abnormal spontaneous brain activity in type 2 diabetes with and without microangiopathy revealed by regional homogeneity. AB - PURPOSE: To investigate whether global spontaneous brain activity changes in type 2 diabetes mellitus (T2DM) patients and these changes vary according to the degree of microangiopathy. MATERIALS AND METHODS: T2DM patients with (M(+), n=26) and without (M(-), n=22) microangiopathy as well as 28 healthy nondiabetic subjects were enrolled in this study. All the subjects completed a resting-state functional magnetic resonance imaging (rs-fMRI) examination and neuropsychological assessment. Regional homogeneity (ReHo) values, representing spontaneous brain activity, were calculated and compared between M(+) and M(-) T2DM patients and nondiabetic controls. RESULTS: In both M(+) and M(-) T2DM patients, ReHo values were decreased in the occipital lobe, temporal lobe, postcentral gyrus, and cerebellum, while increased in the bilateral precuneus, superior/middle frontal gyrus, and insula. Compared with the M(-) group, M(+) patients showed decreased ReHo values in the left cuneus and superior occipital gyrus. The ReHo values in the lingual gyrus/calcarine cortex and MTG were related to clinical parameters in T2DM patients. CONCLUSION: The abnormalities of spontaneous brain activity revealed by ReHo values in both M(+)and M(-) T2DM patients may provide insights into the neurological pathophysiology underlying diabetes-related cognitive impairments. M(+) patients showed more decreased brain activity related to severely impaired function of visual processing and visual memory. PMID- 26860675 TI - Quantitative criteria for the diagnosis of the congenital absence of pericardium by cardiac magnetic resonance. AB - BACKGROUND: Congenital absence of the left ventricular pericardium (LCAP) is a rare and poorly known cardiac malformation. Cardiac Magnetic Resonance (CMR) is generally used for the diagnosis of LCAP because of its high soft tissue contrast, multiplanarity and cine capability, but the diagnosis is usually made by only qualitative criteria. The aim of the present study was to establish quantitative criteria for the accurate diagnosis of LCAP on CMR. METHODS: We enrolled nine consecutive patients affected by LCAP (mean age 26+/-8years, 7 males), 13 healthy controls, 13 patients with dilated cardiomyopathy (DCM), 12 patients with hypertrophic cardiomyopathy (HCM) and 13 patients with right ventricular overload (RVO). All patients underwent CMR. The whole-heart volume was measured in end-systole and end-diastole. Whole-heart volume change (WHVC), was the systo-diastolic change of volume, expressed percentage of the end diastolic volume. The angle of clockwise-rotation of the heart was also measured in the end-diastolic phase of the axial cine stack. RESULTS: The WHVC was significantly higher in LCAP (21.9+/-5.4), compared to healthy subjects (8.6+/ 2.4, p<0.001), DCM (7.1+/-1.8, p<0.001), HCM (9.3+/-2.4, p<0.001) and RVO (8+/ 2.4, p<0.001). The clockwise-rotation was significantly higher in LCAP (76+/-14 degrees ) than healthy controls (40+/-11 degrees , p<0.001), DCM (41+/-5 degrees , p<0.001), HCM (30+/-6 degrees , p<0.001) and RVO (49+/-8 degrees , p<0.001). WHVC had the highest sensitivity (100%) and specificity (100%) for diagnosing LCAP, using a threshold of >13%. CONCLUSIONS: In LCAP the systo-diastolic WHVC was significantly higher than controls, DCM, HCM and RVO patients and resulted an optimal quantitative criteria for the diagnosis of LCAP. PMID- 26860676 TI - Cumulative radiation exposure and associated cancer risk estimates for scoliosis patients: Impact of repetitive full spine radiography. AB - OBJECTIVE: To quantitatively evaluate the cumulative effective dose and associated cancer risk for scoliotic patients undergoing repetitive full spine radiography during their diagnosis and follow up periods. METHODS: Organ absorbed doses of full spine exposed scoliotic patients at different age were computer simulated with the use of PCXMC software. Gender specific effective dose was then calculated with the ICRP-103 approach. Values of lifetime attributable cancer risk for patients exposed at different age were calculated for both patient genders and for Asian and Western population. Mathematical fitting for effective dose and for lifetime attributable cancer risk, as function of exposed age, was analytically obtained to quantitatively estimate patient cumulated effective dose and cancer risk. RESULTS: The cumulative effective dose of full spine radiography with posteroanterior and lateral projection for patients exposed annually at age between 5 and 30 years using digital radiography system was calculated as 15mSv. The corresponding cumulative lifetime attributable cancer risk for Asian and Western population was calculated as 0.08-0.17%. Female scoliotic patients would be at a statistically significant higher cumulated cancer risk than male patients under the same full spine radiography protocol. CONCLUSION: We demonstrate the use of computer simulation and analytic formula to quantitatively obtain the cumulated effective dose and cancer risk at any age of exposure, both of which are valuable information to medical personnel and patients' parents concern about radiation safety in repetitive full spine radiography. PMID- 26860677 TI - Delineation of microhemorrhage in acute hepatic encephalopathy using susceptibility-weighted imaging. AB - INTRODUCTION: Microhemorrhages (MH's) in patients with acute hepatic encephalopathy (AHE) have scarcely been described. This study set out to assess if MH's occur in characteristic locations and frequency in patients with AHE superimposed on chronic liver failure, and to determine if such findings correlate with the clinical and MRI severity. MATERIALS AND METHODS: Over a 4.5 year period, AHE patients with SWI MRI were included. The maximum plasma ammonia level (PAL), number and location of "frank" hemorrhages (>5mm size) or MH's (<5mm) on SWI, and severity of DWI and FLAIR were recorded. Susceptibility foci in the basal ganglia were disregarded, as those changes might represent common mineralization. The presence of MH's was correlated with the MRI and clinical severity. RESULTS: Punctate MH foci were found in 18/38 (47.4%) patients. The most common locations were periventricular white matter (6/38 patients, 15.8%) and cerebral cortex (5/38, 13.2%). Of 47 MH's, only a tiny minority (8.5%) occurred in regions of abnormality on FLAIR or DWI. Both the MRI severity on FLAIR (r=0.420, p=0.013) and DWI (r=0.320, p=0.045) mildly correlated with clinical outcome, but the correlation was not significant after Bonferroni correction. No significant correlation was found between the number of MH's and the clinical score, clinical outcome, FLAIR severity, or DWI severity (range r= 0.083-0.152, p=0.363-0.618). The number of MH's was not significantly different among various vasculopathies. Foci on SWI improved in two patients following liver transplantation. CONCLUSION: SWI-positive foci outside of the basal ganglia (presumed MH's) are present in nearly half of AHE patients, but do not portend outcome. Regions with the most observed MH's were the periventricular white matter, cortical gray matter, and subcortical white matter. PMID- 26860678 TI - Distinguishing hemangiomas from metastases on liver MRI performed with gadoxetate disodium: Value of the extended washout sign. AB - OBJECTIVE: To describe the enhancement pattern of hemangiomas with gadoxetate disodium and propose a new sign - the "extended washout sign" - to diagnose hemangiomas on hepatobiliary MR imaging. MATERIALS AND METHODS: In this retrospective IRB approved study, quantitative and qualitative image analysis of 45 hemangiomas and 37 metastases in 77 patients was performed. Gadoxetate disodium-enhanced MR imaging was obtained during arterial and portal venous phases as well as with delays of 3, 8, and 20min. Lesion signal intensity was measured at each phase. Quantitatively, extended washout was defined as a 10% or greater decrease in signal intensity from 8 to 20min on 3D gradient echo images. Statistical analysis was performed using unpaired Student's t-test. Qualitative analysis was also performed to assess observer confidence based on T2-weighted images, dynamic images, and combined early (8min) and late (20min) hepatobiliary phases. Extended washout was defined as a perceptible change in signal from 8 to 20min. RESULTS: On quantitative analysis, 84% of hemangiomas demonstrated a positive extended washout sign while only 18% of metastases did. Qualitatively, 78% of hemangiomas demonstrated a perceptible change in signal from 8 to 20min, while only 5.4% of metastases did. When extended washout was used in combination with T2 hyperintensity, specificity increased to 100%, with a sensitivity of 87% and area under the curve of 0.99. CONCLUSIONS: When combined with T2 signal intensity, the extended washout sign can be used to increase accuracy of differentiating hemangiomas from metastases on gadoxetate disodium-enhanced MRI. PMID- 26860679 TI - One-mSv CT colonography: Effect of different iterative reconstruction algorithms on radiologists' performance. AB - PURPOSE: To analyze the effect of different reconstruction algorithms on image noise and radiologists' performance at ultra-low dose CT colonography (CTC) in human subjects. MATERIALS AND METHODS: This retrospective study had institutional review board approval, with waiver of the need to obtain informed consent. CTC and subsequent colonoscopy were performed at the same day in 28 patients. CTC was scanned at the supine/prone positions using 120/100kVp and fixed 10mAs, and reconstructed using filtered back projection (FBP), adaptive statistical iterative reconstruction (ASIR), and model-based IR (Veo) algorithms. Size specific dose estimates (SSDE) and effective radiation doses were recorded. Image noise was compared among the three datasets using repeated measures analysis of variance (ANOVA). Per-polyp sensitivity and figure-of-merits were compared among the datasets using the McNemar test and jackknife alternative free-response receiver operating characteristic (JAFROC) analysis, respectively, by one novice and one expert reviewer in CTC. RESULTS: Mean SSDE and effective radiation dose of CTC were 1.732mGy and 1.002mSv, respectively. Mean image noise at supine/prone position datasets was significantly lowest with Veo (17.2/13.3), followed by ASIR (52.4/38.9) and FBP (69.9/50.8) (P<0.0001). Forty-two polyps in 25 patients were reference polyps. For both readers, per-polyp sensitivity of all 42 polyps was highest with Veo reconstruction (81.0%, 64.3%), followed by ASIR (73.8%, 54.8%) and FBP (57.1%, 50.0%) with statistical significance between Veo and FBP for reader 1 (P=0.002). JAFROC analysis revealed that the figure-of-merit for the detection of polyps was highest with Veo (0.917, 0.786), followed by ASIR (0.881, 0.750) and FBP (0.750, 0.746) with statistical significances between Veo or ASIR and FBP for reader 1 (P<0.05). CONCLUSION: One-mSv CTC was not feasible using the standard FBP algorithm. However, diagnostic performance expressed as per-polyp sensitivity and figures-of-merit can be improved with the application of IR algorithms, particularly Veo. PMID- 26860680 TI - Superb microvascular imaging for the detection of parenchymal perfusion in normal and undescended testes in young children. AB - OBJECTIVES: To compare the detectability of perfusion difference between normal and undescended testes (UDT) in young children using conventional Power Doppler Imaging (PDI) and Superb Microvascular Imaging (SMI). METHODS: We prospectively performed testicular ultrasonography including PDI and SMI for the evaluation of microvascular flow in young children. Microvascular flow was categorized into four grades (grade 0-4). Statistical analysis was performed to compare the differences between undescended and normal testes. RESULTS: We imaged 40 testes from 20 boys (age, 2-29 months). Testes sizes and volumes were similar between the 29 normal and 11 UDT. PDI demonstrated low grade flow in most normal (19/29) and UDT (11/11) without difference (P=0.130). However, SMI detected differences in flow grades between normal and UDT (P<0.001). In univariate analysis, age (odds ratio [OR], 0.829; P=0.012) and low grade flow on SMI (OR of grade 0, 51.886 with P<0.001 and OR of grade 1, 14.29 with P=0.017) were associated with UDT. These parameters were also significant in multivariate analysis with larger area under the curve, compared with the results using PDI (0.892 vs. 0.726, P=0.002). CONCLUSIONS: SMI can detect perfusion difference between normal and UDT in young children better than PDI. PMID- 26860681 TI - Residual low ADC and high FA at the resection margin correlate with poor chemoradiation response and overall survival in high-grade glioma patients. AB - PURPOSE: We hypothesized that ADC and FA of enhancing tumor (ET) and/or non enhancing tumor (NT) adjacent to the operative resection margin before and during temozolomide and/or chemoradiation may allow prediction of chemoradiation response and patient survival. MATERIAL AND METHODS: DTI was acquired in 37 patients with newly diagnosed HGG at two time points: after resection at the time of pre-RT planning MRI (Baseline) and after 30Gy of radiation therapy (mid-RT). ADC and FA at each time point and change in ADC and FA between the two time points were assessed by hot spot method in both residual ET and NT within 2cm of the resection margin and correlated with overall survival (OS) using receiver operating characteristics (ROC) area under curve (AUC) analysis and log-rank testing. RESULTS: At baseline NT ADC<104*10(-5)mm(2)/s was strongly correlated with shorter 15 month OS (95% CI: 227-412 days vs 492-695 days) compared to patients with higher ADC (AUC 0.82). There was good separation between the groups and significance at log-rank testing (p=0.0002). Baseline NT FA>0.257 also correlated with shorter OS (95% CI: 300-515 days vs 438-686 days), compared with patients with lower FA (AUC 0.74), but there was considerable overlap between the groups and non-significance at log-rank testing (p=0.089). Residual ET ADC increased significantly (p=0.0004) and FA decreased significantly (p=0.03) for all patients during early RT but the change in ADC and FA was less strongly correlated with OS than baseline NT metrics. CONCLUSION: Post-operative pre radiation baseline low ADC in non-enhancing tumor at the resection margin correlates strongly with worse treatment response and decreased overall survival in a heterogeneous sample of high grade glioma patients treated with radiation and/or temozolamide chemoradiation. PMID- 26860682 TI - Noise-optimized advanced image-based virtual monoenergetic imaging for improved visualization of lung cancer: Comparison with traditional virtual monoenergetic imaging. AB - PURPOSE: To assess the effect of a noise-optimized image-based virtual monoenergetic imaging (VMI+) algorithm in direct comparison with the traditional VMI technique and standard linearly-blended images emulating 120-kVp acquisition (M_0.3) on image quality at dual-energy CT in patients with lung cancer. MATERIALS AND METHODS: Dual-source dual-energy CT examinations of 48 patients with biopsy-proven primary (n=31) or recurrent (n=20) lung cancer were evaluated. Images were reconstructed as M_0.3, and VMI+ and traditional VMI series at 40, 55, and 70keV. Attenuation of tumor, descending aorta, pulmonary trunk, latissimus muscle, and noise were measured. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Five-point scales were used by three observers to subjectively evaluate general image impression, tumor delineation, image sharpness, and image noise. RESULTS: Background noise was consistently lower with VMI+ compared to VMI at all keV levels (all p<0.0001) and M_0.3 (all p<=0.0004). Tumor SNR and CNR peaked in the 40keV VMI+ series, significantly higher compared to all VMI and M_0.3 series (all p<0.0008). Observers preferred the 55keV VMI+ series regarding general image impression and tumor delineation compared to all other series (all p<0.0001). Image sharpness and image noise ratings were highest in the 55keV VMI+ and 70keV VMI and VMI+ reconstructions. CONCLUSIONS: Tumor CNR peaked at 40keV VMI+ while observers preferred 55keV VMI+ series overall other series for dual-energy CT of lung cancer. The noise-optimized VMI+ technique showed significantly lower background noise and higher SNR and CNR compared to the traditional VMI technique at matching keV levels. PMID- 26860683 TI - Role of computed tomography on large B-cell non-Hodgkin's lymphoma follow-up and the risk of radiation-induced neoplasm: A retrospective cohort study. AB - INTRODUCTION: To evaluate the role of surveillance computed tomography (CT) in detection of tumor relapse after complete remission for large-cell lymphoma and to estimate the cancer risk related to those examinations. MATERIALS AND METHODS: We retrospectively identified the cases of large-cell lymphoma diagnosed at our institution during a fifteen years period. We extracted from charts the information needed. Agreement between clinical and radiological evaluation for relapse detection was determined with index kappa and McNemar tests. We analysed the surveillance CT examinations performed to the patients in complete remission with no recurrence during the follow-up period and we estimated the life attributable risk (LAR) of radiation-induced cancer above base line using the approach of the Biological Effects of Ionizing Radiation (BEIR) VII. RESULTS: 184 patients with biopsy confirmed large-cell lymphoma were included. Complete remission was attained in 125 patients. After a median follow-up of 93.73 months, 97 of them remain in remission. Relapse was confirmed in 28 patients; only 3 of them were asymptomatic. Kappa and McNemar analyses revealed good agreement for diagnosis of recurrence and significant difference for exclusion of relapse. Patients in remission received a median of 6 surveillance CT examinations. Fifty seven patients had total cumulative doses greater than 100mSv. The mean increase in estimated radiation-induced cancer risk was 0.5%. CONCLUSION: Our results suggest that periodic CT examinations have a limited role in detecting relapse in large-cell lymphoma as the clinical surveillance dictates the patient management. PMID- 26860684 TI - Positron annihilation spectroscopy of vacancy-related defects in CdTe:Cl and CdZnTe:Ge at different stoichiometry deviations. AB - Positron annihilation spectroscopy (PAS) was used to examine the effect of defined Cd-rich and Te-rich annealing on point defects in Cl-doped CdTe and Ge doped CdZnTe semi-insulating single crystals. The as-grown crystals contain open volume defects connected with Cd vacancies . It was found that the Cd vacancies agglomerate into clusters coupled with Cl in CdTe:Cl, and in CdZnTe:Ge they are coupled with Ge donors. While annealing in Cd pressure reduces of the density, subsequent annealing in Te pressure restores . The CdTe:Cl contains negatively charged shallow traps interpreted as Rydberg states of A-centres and representing the major positron trapping sites at low temperature. Positrons confined in the shallow traps exhibit lifetime, which is shorter than the CdTe bulk lifetime. Interpretation of the PAS data was successfully combined with electrical resistivity, Hall effect measurements and chemical analysis, and allowed us to determine the principal point defect densities. PMID- 26860685 TI - Taking the patient's body surface area into account when estimating GFR. PMID- 26860686 TI - Effect of bixin on DNA damage and cell death induced by doxorubicin in HL60 cell line. AB - Bixin is a natural red pigment extracted from annatto. Although it is widely used as a coloring agent in food, there are few studies about the effect of this carotenoid on DNA. This study aimed to investigate the effects of bixin on cytotoxicity and genotoxicity induced by doxorubicin in HL60 cells. At concentrations above 0.3 MUg/mL, bixin demonstrated cytotoxic effects in HL60 cells. Furthermore, this carotenoid was neither mutagenic nor genotoxic to HL60 cells and reduced the DNA damage induced by doxorubicin. Bixin and doxorubicin showed no apoptotic effect in HL60 cells, but the simultaneous combined treatments showed an increase in the percentage of apoptotic cells. In conclusion, our results showed that bixin modulates the cytotoxicity of doxorubicin via induction of apoptosis. The results of this study provide more knowledge about the toxic effects of anticancer treatments and how the natural compounds can be useful on these therapeutic approaches. PMID- 26860687 TI - Intentional poisoning among elderly people-residents of a large urban agglomeration in Poland. AB - Poisoning is considered a significant health problem among elderly people in Poland. This report refers to patients treated for poisonings at the Toxicology Unit, Lodz, Poland, during the period 2008-2012. The data to be analyzed were obtained from medical records of elderly people. A group of 1167 patients aged 60+ was selected. The number of intentional poisonings in the group of patients was 417, which accounted for 35.7% of all poisonings among the elderly people. Patients attempting intentional poisonings included 301 (72.2%) women and 116 (27.8%) men. The most common cause of intentional poisonings were drugs-96.6% (n = 403). Benzodiazepines (46.9%) dominated among the intentional poisoning by drugs. During the analyzed 5 years, 80.3% (n = 335) were suicidal poisonings and 19.7% (n = 82) were demonstrative poisonings. Cardiovascular disease, which was diagnosed among 53.5% of the patients, was the most common physical illness. In conclusion, drugs are the most frequent type of the toxic agent responsible for poisoning cases among the elderly people. In this situation, the role of family doctors is very important: they should prescribe medicines in amounts not greater than absolutely necessary and maybe more often recommend psychiatric care for the elderly patients. PMID- 26860688 TI - Subchronic toxicology of tetrabromobisphenol A in rats. AB - Tetrabromobisphenol A (TBBPA) is used to protect a wide range of electrical and electronic equipment, consumer electronics and office and communication equipment from catching fire. TBBPA reacts covalently with other monomers becoming an integral part of the cross-linked molecular structure. This study was conducted to evaluate the subchronic toxicity of TBBPA administered by gavage daily for 13 weeks at 0, 100, 300, and 1000 mg/kg/day in male and female CD(r) rats. A 6-week post-treatment control and 1000 mg/kg/day recovery groups were included. TBBPA exerted no marked effect on the rate of mortality, clinical signs, body or organ weights, feed consumption, histopathology, urinalysis, ophthalmology, and neurological outcomes in a functional observation battery, motor activity, serum thyroid stimulating hormone, serum triiodothyronine, or other serum chemistries. Although differences were observed for bilirubin and alkaline phosphatase, the observed alterations were within the normal range and thus were neither biologically or toxicologically meaningful. The single thyroid-related parameter affected by TBBPA was a reduction in serum thyroxine levels, but the decrease was not of sufficient magnitude to induce other more sensitive indicators of thyroid perturbation. The No Observed Adverse Effect Level was at least 1000 mg/kg/day, the highest dose tested. Based on an upper bound aggregate exposure for adults estimated by the European Union, the margin of exposure is approximately 5000, suggesting that, for the endpoints examined in this study, exposure to TBBPA presents a reasonable certainty of no harm. PMID- 26860689 TI - Pyrrolidine dithiocarbamate attenuates paraquat-induced acute pulmonary poisoning in vivo via transforming growth factor beta1 and nuclear factor kappaB pathway interaction. AB - Paraquat (PQ) exposure could cause pulmonary fibrosis. The aim of this study was to investigate the protective effect of pyrrolidine dithiocarbamate (PDTC) in an acute PQ poison model. One hundred and forty-four Sprague Dawley rats were equally divided into three experimental groups: control group, PQ group, and PQ + PDTC group. At days 1, 3, 7, 14, 28, and 56 of treatment, the serum levels of transforming growth factor beta1 (TGF-beta1), the levels of hydroxyproline, the protein expression of nuclear factor kappaB (NF-kappaB) pathway, and histopathological change in lung tissue were assessed. The survival rate of rats treated with PQ + PDTC was increased compared with that of rats treated only with PQ (p < 0.05), and the occurrence of pathological changes was dramatically attenuated in the PQ + PDTC group. The serum levels of TGF-beta1 and the hydroxyproline levels in the PQ group were significantly increased in a time dependent manner compared with those in the control and PQ + PDTC groups on days 7, 14, 28, and 56 (p < 0.05). Additionally, the protein levels of NF-kappaB proteins p65, inhibitor of kappaB (IkappaB) kinase (IKKbeta, and IkappaB-alpha were significantly downregulated in the PQ + PDTC group as determined by array analysis. The present findings suggest that overexpression of TGF-beta1 may play an important role in PQ-induced lung injury and that PDTC, a strong NF-kappaB inhibitor, can rescue PQ-induced pulmonary fibrosis by influencing the protein expression of NF-kappaB pathway. PMID- 26860690 TI - A comprehensive toxicity study of zinc oxide nanoparticles versus their bulk in Wistar rats: Toxicity study of zinc oxide nanoparticles. AB - The purpose of this study was to characterize the zinc oxide nanoparticles (ZnO NPs) and their bulk counterpart in suspensions and to access the impact of their acute oral toxicity at doses of 300 and 2000 mg/kg in healthy female Wistar rats. The hematological, biochemical, and urine parameters were accessed at 24 and 48 h and 14 days posttreatment. The histopathological evaluations of tissues were also performed. The distribution of zinc content in liver, kidney, spleen, plasma, and excretory materials (feces and urine) at 24 and 48 h and 14 days posttreatment were accessed after a single exposure at dose of 2000 mg/kg body weight. The elevated level of alanine amino transferase, alkaline phosphatase, lactate dehydrogenase, and creatinine were observed in ZnO-NPs at a dose of 2000 mg/kg at all time points. There was a decrease in iron levels in all the treated groups at 24 h posttreatment as compared to control groups but returned to their normal level at 14 days posttreatment. The hematological parameters red blood cells, hemoglobin, hematocrit, platelets, and haptoglobin were reduced at 48 h posttreatment at a dose of 2000 mg/kg ZnO-NPs and showed hemolytic condition. All the treated groups were comparable to control group at the end of 14 days posttreatment. The zinc concentration in the kidney, liver, plasma, feces, and urine showed a significant increase in both groups as compared to control. This study explained that ZnO-NPs produced more toxicological effect as compared to their bulk particles as evidenced through alteration in some hemato-biochemical parameters and with few histopathological lesions in liver and kidney tissues. PMID- 26860691 TI - Evaluation of leptin, adiponectin, and ghrelin levels in patients with acne vulgaris. AB - BACKGROUND: The research evaluating adipokines are very few in patients with acne vulgaris. The hypothesis that hyperinsulinemic and high glycemic index diet plays a role in the pathogenesis of acne is still controversial. In this study, we aimed to evaluate adipokines such as leptin (L), adiponectin (A), ghrelin and A levels, and A/L rates that indicate insulin resistance in nonobese patients with severe acne vulgaris. MATERIAL AND METHOD: Thirty patients who are nonobese with moderate acne vulgaris, aged 18 to 25 years, and 15 age-sex compatible controls were included in our study. The acne lesions were assessed using the Global Acne Grading Scale (GAGS). All participants were evaluated for the parameters that may affect the metabolism of serum L, A, and ghrelin levels in blood, and their body mass index were calculated. The significance level was determined as p <= 0.05. RESULTS: Of the 30 patients, 17 were women and 13 were men. The mean age was 20.60 years and the mean duration of the disease were 2.8 years. All of patients had moderate acne vulgaris (GAGS 19-30). Of the 15 controls, 11 were women and 4 were men. The mean age was 21.20 years. There were not a statistically significant difference in L, ghrelin, A levels, and A/L ratio between the two groups. CONCLUSIONS: Adipokines may have a role in the pathogenesis of acne vulgaris. L, A, ghrelin, and insulin resistance may not participate in the responsible mechanisms in nonobese patients with moderate acne vulgaris. PMID- 26860693 TI - EDITORIAL: Repurposing Niacin as Antiplatelet Drug? PMID- 26860692 TI - Uniform Nickel Vanadate (Ni3V2O8) Nanowire Arrays Organized by Ultrathin Nanosheets with Enhanced Lithium Storage Properties. AB - Development of three-dimensional nano-architectures on current collectors has emerged as an effective strategy for enhancing rate capability and cycling stability of the electrodes. Herein, a novel type of Ni3V2O8 nanowires, organized by ultrathin hierarchical nanosheets (less than 5 nm) on Ti foil, has been obtained by a two-step hydrothermal synthesis method. Studies on structural and thermal properties of the as-prepared Ni3V2O8 nanowire arrays are carried out and their morphology has changed obviously in the following heat treatment at 300 and 500 degrees C. As an electrode material for lithium ion batteries, the unique configuration of Ni3V2O8 nanowires presents enhanced capacitance, satisfying rate capability and good cycling stability. The reversible capacity of the as-prepared Ni3V2O8 nanowire arrays reaches 969.72 mAh . g(-1) with a coulombic efficiency over 99% at 500 mA . g(-1) after 500 cycles. PMID- 26860694 TI - Conventional and New Antiepileptic Drugs on Vitamin D and Bone Health: What We Know to Date? AB - The treatment with antiepileptic drugs (AEDs), in particular conventional drugs, induces an increased risk of fractures in women and in epileptic patients in treatment with AEDs for more than 12 years. A supplementation with calcium and vitamin D is suggested in patients chronically treated with some AEDs and there are recommendations to do so. The lack of significant conclusive evidence about the effects of conventional and newer AEDs on bone metabolism needs for more clinical studies in order to perform an appropriate use of calcium and vitamin D supplementation in young and ederly epileptic patients. PMID- 26860695 TI - Theory and practical based approach to chronic total occlusions. AB - Coronary chronic total occlusions (CTOs) represent the most technically challenging lesion subset that interventional cardiologists face. CTOs are identified in up to one third of patients referred for coronary angiography and remain seriously undertreated with percutaneous techniques. The complexity of these procedures and the suboptimal success rates over a long period of time, along with the perception that CTOs are lesions with limited scope for recanalization, account for the underutilization of CTO Percutaneous Coronary Intervention (PCI). During the last years, dedicated groups of experts in Japan, Europe and United States fostered the development and standardization of modern CTO recanalization techniques, achieving success rates far beyond 90%, while coping with lesions of increasing complexity. Numerous studies support the rationale of CTO revascularization following documentation of viability and ischemia in the territory distal to the CTO. Successful CTO PCI provide better tolerance in case of future acute coronary syndromes and can significantly improve angina and left ventricular function. Randomized trials are on the way to further explore the prognostic benefit of CTO revascularization. The following review reports on the theory and the most recent advances in the field of CTO recanalization, in an attempt to promote a more balanced approach in patients with chronically occluded coronary arteries. PMID- 26860697 TI - Arachnoid cyst of the fallopian canal and geniculate ganglion area: our experience of 9 cases. PMID- 26860696 TI - Functional analysis of long intergenic non-coding RNAs in phosphate-starved rice using competing endogenous RNA network. AB - Long intergenic non-coding RNAs (lincRNAs) may play widespread roles in gene regulation and other biological processes, however, a systematic examination of the functions of lincRNAs in the biological responses of rice to phosphate (Pi) starvation has not been performed. Here, we used a computational method to predict the functions of lincRNAs in Pi-starved rice. Overall, 3,170 lincRNA loci were identified using RNA sequencing data from the roots and shoots of control and Pi-starved rice. A competing endogenous RNA (ceRNA) network was constructed for each tissue by considering the competing relationships between lincRNAs and genes, and the correlations between the expression levels of RNAs in ceRNA pairs. Enrichment analyses showed that most of the communities in the networks were related to the biological processes of Pi starvation. The lincRNAs in the two tissues were individually functionally annotated based on the ceRNA networks, and the differentially expressed lincRNAs were biologically meaningful. For example, XLOC_026030 was upregulated from 3 days after Pi starvation, and its functional annotation was 'cellular response to Pi starvation'. In conclusion, we systematically annotated lincRNAs in rice and identified those involved in the biological response to Pi starvation. PMID- 26860698 TI - The impact of daycare attendance on outdoor free play in young children. AB - Background: Outdoor free play is important for healthy growth and development in early childhood. Recent studies suggest that the majority of time spent in daycare is sedentary. The objective of this study was to determine whether there was an association between daycare attendance and parent-reported outdoor free play. Methods: Healthy children aged 1-5 years recruited to The Applied Research Group for Kids! (TARGet Kids!), a primary care research network, were included. Parents reported daycare use, outdoor free play and potential confounding variables. Multivariable linear regression was used to determine the association between daycare attendance and outdoor free play, adjusted for age, sex, maternal ethnicity, maternal education, neighborhood income and season. Results: There were 2810 children included in this study. Children aged 1 to <3 years (n = 1388) and >=3 to 5 years (n = 1284) who attended daycare had 14.70 min less (95% CI 20.52, -8.87; P < 0.01) and 9.44 min less (95% CI -13.67, -5.20; P < 0.01) per day of outdoor free play compared with children who did not attend daycare, respectively. Conclusions: Children who spend more time in daycare have less parent-reported outdoor free play. Parents may be relying on daycare to provide opportunity for outdoor free play and interventions to promote increased active play opportunities outside of daycare are needed. PMID- 26860699 TI - Validity of the 16-metre PACER and six-minute walk test in adults with Down syndrome. AB - PURPOSE: The purpose was to establish criterion-related validity of the 16-metre PACER and six-minute walk distance (6MWD) tests to VO2 peak as well as predictors of VO2 peak in adults with Down syndrome (DS). METHODS: Adults with DS (24 males and 19 females) aged 18-50 years performed the three aerobic tests on non consecutive days during a one-week period. To assess validity, peak oxygen uptake was measured directly on a motorized treadmill. Pearson-product moment correlations were performed. Predictors of VO2 peak were assessed with a stepwise multiple regression analysis. Agreement between PACER and VO2 peak was assessed by Bland-Altman plot. RESULTS: Linear regression revealed that the PACER (R(2 )=( )0.86) and the 6MWD (R(2 )=( )0.75) were significantly related to VO2 peak (p < 0.05). Both the 16-metre PACER and the 6MWD significantly correlated with VO2 peak for adults with DS. The relationship was stronger for the 16-metre shuttle run test (r = 0.87) than the 6MWD (r = 0.78). The correlation between VO2 peak and both field tests, controlling for age, gender and BMI, remained significant (r > 0.7; p < 0.05). PACER, 6MWD and BMI are significant predictors of VO2 peak (p < 0.05). CONCLUSION: The 16-metre PACER and 6MWD are valid field tests for predicting aerobic capacity in adults with DS. Implications for Rehabilitation The 16-metre PACER and 6MWD tests are safe and feasible for use in adults with DS. Both tests are valid indicators of cardio-respiratory fitness as assessed by moderate-to-strong coefficients of determination and correlation coefficients. Both field tests along with BMI are predictors of aerobic capacity. PMID- 26860700 TI - Non-alcoholic Fatty Liver Disease (NAFLD) is associated with impairment of Health Related Quality of Life (HRQOL). AB - BACKGROUND: NAFLD impacts patient reported outcomes (PROs). Our aim was to assess the impact of NAFLD on patients' HRQOL. METHODS: National Health and Nutrition Examination Survey (NHANES) 2001-2011 data were used to identify adult patients with NAFLD [Fatty Liver Index (FLI) > 60 in absence of other liver disease and excessive alcohol >20 g/day for men, >10 g/day for women]. Patients with other chronic diseases (ex. HIV, cancer, end-stage kidney disease) were excluded. Subjects without any of these conditions were healthy controls. HCV RNA (+) patients were HCV-controls. All patients completed NHANES HRQOL-4 questionnaire. Linear regression determined the association between NAFLD and HRQOL components adjusting for age, gender, race, and BMI. RESULTS: Participants with complete data were included (n = 9661); 3333 NAFLD (age 51 years and BMI 34 kg/m(2)); 346 HCV+ (age 49 years; BMI 27 kg/m(2)) and 5982 healthy controls (age 48 years and BMI 26 kg/m(2)). The proportion of subjects rating their health as "fair" or "poor" in descending order were HCV controls (30 %) NAFLD (20 %) and healthy controls (10 %) (p < 0.001). HRQOL-4 components scores 2-4 were lowest for HCV, followed by NAFLD and then healthy controls (p-values p = 0.011 to < .0001). After adjustment for age, gender, race, and BMI, NAFLD patients were 18-20 % more likely to report days when their physical health wasn't good or were unable to perform daily activities as a result (p < .0001). CONCLUSIONS: NAFLD causes impairment of HRQOL. As NAFLD is becoming the most important cause of CLD, its clinical and PRO impact must be assessed. PMID- 26860703 TI - miR-3940-5p enhances homologous recombination after DSB in Cr(VI) exposed 16HBE cell. AB - Hexavalent chromium (Cr(VI)) is a well-recognized human carcinogen, yet the molecular mechanisms by which cause human cancer are still not well understood. MicroRNAs (miRNAs), which are small non-coding RNAs, are involved in carcinogenesis and DNA damage repair. Previous occupational population study showed that hexavalent chromium (Cr(VI)) downregulated plasma miR-3940-5p level, and a low miR-3940-5p level was associated with high XRCC2 expression in lymphocytes, indicating that miR-3940-5p maybe play a protective effect in Cr(VI) induced DNA damage. Here we investigated miR-3940-5p expression and its roles in DNA repair in Cr(VI)-treated 16HBE cells. miR-3940-5p change was detected by qRT PCR. Rad51 foci formation and double strand break (DSB) were investigated to assess homologous recombination repair (HR) capacity by Immunofluorescent assay and Neutral Comet assay. XRCC2 expression was also evaluated after miRNA oligonucleotides transfection using Western blot. Cr(VI) treatment suppressed miR 3940-5p level in 16HBE cells. miR-3904-5p mimic downregulated XRCC2 expression. As a result, the formation of Rad51-foci was inhibited and DSB repair was prolonged. The results indicate that miR-3940-5p plays a protective effect in Cr(VI) induced DNA damage. PMID- 26860702 TI - Origin of the gender differences of the natural resistance to antivitamin K anticoagulants in rats. AB - Vitamin K antagonists (VKA) are used either in human medicine to prevent thromboembolic disorders or as rodenticides for pest control management. In rodents, female rats are described to be more tolerant to the action of vitamin K antagonists than males. Nevertheless, the mechanism of this greatest tolerance is still unknown and this study aims to identify the origin of this greatest tolerance after VKA administration. Therefore, difethialone, one of the most powerful VKA was used in this study. A possible difference in the pharmacokinetics of difethialone between males and females was first investigated. The determination of the pharmacokinetic parameters allowed to exclude a pharmacokinetic origin of the greatest tolerance of females to VKA. Thus, a natural resistance to difethialone of the liver VKOR activity, which is the target of VKA, was thus explored in females. The determination of Ki towards difethialone in liver microsomes allowed to also exclude this hypothesis. Therefore, equipment in vitamin K-dependent clotting factors and properties of vitamin K-dependent clotting factors were explored. Basal activity of clotting factors VII and X were found significantly higher in females of respectively 43% and 21%. Moreover, after VKA administration, half-lives of clotting factors II and X were found significantly longer in females of respectively 27% and 10% and a lag time of 4h before the beginning of the decay of factor VII was observed only in females after difethialone administration. The greater tolerance of female rats to VKA is thus due a stronger basal pool of vitamin K-dependent clotting factors VII and X and to a slower decline of vitamin K-dependent clotting factors II, VII and X after VKA administration. PMID- 26860704 TI - Celebrating Soft Matter's 10th Anniversary: Simplicity in complexity--towards a soft matter physics of caramel. AB - Caramel is a mixture of sugars, milk proteins, fat and water cooked at high temperatures to initiate Maillard reactions. We study caramels as 'active emulsion-filled protein gels', in which fat droplets are chemically-bonded to a background gel matrix of cross-linked proteins in a concentrated aqueous sugar solution. We delimit a 'caramel region' in composition space. Oscillatory rheology within this region reveals that we can superpose the mechanical spectra of our caramels onto a single pair of G'(omega), G''(omega) master curves using time-composition superposition (tCS) over 12 decades of frequency, so that these caramels are instances of an underlying 'universal material'. This insight constrains the molecular mechanisms for structure formation, and implies that measuring a couple of parameters will suffice to predict the rheology of our caramels over 12 orders of magnitude in frequency. PMID- 26860701 TI - Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increases human hepatic stellate cell activation. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a halogenated aromatic hydrocarbon that elicits toxicity through the aryl hydrocarbon receptor (AhR). In the liver, gross markers of TCDD toxicity are attributed to AhR activation in parenchymal hepatocytes. However, less is known regarding the consequences of TCDD treatment on non-parenchymal cells in the liver. Hepatic stellate cells (HSCs) are non parenchymal cells that store vitamin A when quiescent. Upon liver injury, activated HSCs lose this storage ability and instead function in the development and maintenance of inflammation and fibrosis through the production of pro inflammatory mediators and collagen type I. Reports that TCDD exposure disrupts hepatic retinoid homeostasis and dysregulates extracellular matrix remodeling in the liver led us to speculate that TCDD treatment may disrupt HSC activity. The human HSC line LX-2 was used to test the hypothesis that TCDD treatment directly activates HSCs. Results indicate that exposure to 10nM TCDD almost completely inhibited lipid droplet storage in LX-2 cells cultured with retinol and palmitic acid. TCDD treatment also increased LX-2 cell proliferation, expression of alpha smooth muscle actin, and production of monocyte chemoattractant protein-1 (MCP 1), all of which are characteristics of activated HSCs. However, TCDD treatment had no effect on Col1a1 mRNA levels in LX-2 cells stimulated with the potent profibrogenic mediator, transforming growth factor-beta. The TCDD-mediated increase in LX-2 cell proliferation, but not MCP-1 production, was abolished when phosphoinositide 3-kinase was inhibited. These results indicate that HSCs are susceptible to direct modulation by TCDD and that TCDD likely increases HSC activation through a multi-faceted mechanism. PMID- 26860705 TI - "Any fool can make a rule and any fool will mind it". AB - In principle, accurate guideline recommendations should lead to optimal management based on a secure diagnosis. However, current IPF diagnostic guidelines do not meet the needs of a major sub-group (possibly the majority) of patients with idiopathic pulmonary fibrosis (IPF). A great many IPF patients have HRCT appearances of "possible UIP". A surgical biopsy is very often impracticable due to age, disease severity, co-morbidities or patient refusal. A guideline based diagnosis cannot be made in these patients, although the diagnosis is often obvious. Inflexible diagnostic criteria, although essential for treatment trials, must necessarily be structured around an inflexible diagnostic algorithm. With this approach, non-standardised information (i.e. not available in all patients) must be omitted, including observed disease behaviour prior to and on treatment, findings on bronchoalveolar lavage, likelihoods in relation to age and a wealth of ancillary clinical information. However, when a diagnosis cannot be made using guideline criteria, a probable or highly probable "working diagnosis" of IPF can and should be made in most IPF patients by means of clinical reasoning, integrating all available non-standardised information. PMID- 26860708 TI - Immediate percutaneous coronary intervention in NSTE-ACS: the sun is not hurried by early risers. PMID- 26860707 TI - Prevalence of blood type A and risk of vascular complications following transcatheter aortic valve implantation. AB - OBJECTIVES: To assess the prevalence of blood type A among patients referred for transcatheter aortic valve implantation (TAVI) and whether it is related to vascular complications. BACKGROUNDS: Vascular complications following TAVI are associated with adverse outcomes. Various blood types, particularly type A, have been shown to be more prevalent in cardiovascular diseases and to be related to prognosis. METHODS: The prevalence of various blood types in a cohort of 491 consecutive patients who underwent TAVI was compared with a control group of 6500 consecutive hospitalised patients. The prevalence and predictors of vascular complications and bleeding events were evaluated in the blood type A group and were compared with non-type A patients. RESULTS: The mean age of TAVI patients was 83 +/- 6 years, and 40 % were males. Patients were divided into two groups: blood type A (n = 220) and non-type A (n = 271). Type A was significantly more prevalent in the TAVI group than in the control group (45 vs. 38 %, p = 0.023). Compared with the non-type A group, patients with blood type A had more major and fatal bleeding (14.5 vs. 8.1 %, p = 0.027) and more vascular complications (any vascular complication: 24.5 vs. 15.9 % p = 0.016; major vascular complications: 12.3 vs. 7 % p = 0.047). In a multivariable analysis, blood type A emerged as a significant and independent predictor for vascular complications and bleeding events. CONCLUSIONS: Blood type A is significantly more prevalent in TAVI patients than in the general population and is related to higher rates of vascular and bleeding complications. PMID- 26860706 TI - Stigma in the context of schools: analysis of the phenomenon of stigma in a population of university students. AB - BACKGROUND: Students have stereotyped views about people with mental illness. In particular, they believe that these persons are incurable, dangerous, unpredictable and responsible for their condition. This study aims to investigate the levels of public stigma in an Italian university population. METHODS: The Attribution Questionnaire 27 - Italian Version (AQ-27-I) was administered to a sample of students from the Faculty of Medicine and Surgery of the University of Modena and Reggio Emilia. After examining the psychometric characteristics of the AQ-27-I (Cronbach's Alpha and Confirmatory Factor Analysis), multiple linear regression analyses were carried out to identify the predictors of stigmatizing attitudes in this population. RESULTS: Three hundred and eleven students completed the questionnaire, with a response rate of 32.81 % (out of the 948 contacted by email). The AQ-27-I showed good psychometric properties with an alpha = .68, and the fit indices of the models that partially supported the factor structure and paths. The two variables identified as possible predictors of stigmatizing attitudes (total score of AQ-27-I) were age and time spent reading newspapers. CONCLUSIONS: Antistigma campaigns are needed in university contexts, targeted in particular to students in health professions. PMID- 26860709 TI - Impact of percutaneous coronary intervention timing on 5-year outcome in patients with non-ST-segment elevation acute coronary syndromes. The 'wait a day' approach might be safer. AB - BACKGROUND: The OPTIMA trial was a randomised multicentre trial exploring the influence of the timing of percutaneous coronary intervention (PCI) on patient outcomes in an intermediate to high risk non-ST-elevation acute coronary syndrome (NSTE-ACS) population. In order to decide the best treatment strategy for patients presenting with NSTE-ACS, long-term outcomes are essential. METHODS: Five-year follow-up data from 133 of the 142 patients could be retrieved (94 %). The primary endpoint was a composite of death and spontaneous myocardial infarction (MI). Spontaneous MI was defined as MI occurring more than 30 days after randomisation. Secondary endpoints were the individual outcomes of death, spontaneous MI or re-PCI. RESULTS: No significant difference with respect to the primary endpoint was observed (17.8 vs. 10.1 %; HR 1.55, 95 % CI: 0.73-4.22, p = 0.21). There was no significant difference in mortality rate. However, spontaneous MI was significantly more common in the group receiving immediate PCI (11.0 vs. 1.4 %; HR 4.46, 95 % CI: 1.21-16.50, p = 0.02). We did not find a significant difference between the groups with respect to re-PCI rate. CONCLUSION: There was no difference in the composite of death and spontaneous MI. The trial suggests an increased long-term risk of spontaneous MI for patients treated with immediate PCI. PMID- 26860710 TI - Congruency precues moderate item-specific proportion congruency effects. AB - The item-specific proportion congruency (ISPC) effect refers to the reduction in the Stroop effect for items (e.g., words) that mostly appear in an incongruent format, as compared to items that mostly appear in a congruent format. It is thought to demonstrate reactive control of word-reading processes. In the present study, we tested the hypothesis that using explicit, trial-by-trial congruency precues to proactively guide attention during a color-word Stroop task could reduce the otherwise robust ISPC effect. In Experiment 1, the precueing manipulation was employed alongside a manipulation traditionally thought to influence proactive control of word-reading processes (i.e., list proportion congruence [list PC]). Precueing participants with 100 %-valid precues eliminated both the ISPC effect and the list PC effect. In Experiment 2, we used 70 %-valid congruency precues to direct participants to generally expect conflict or congruence on a given trial. ISPC effects were selectively reduced when the participants expected conflict. These results suggest that precueing influences engagement in proactive control and, as a result, reduces the impact of item specific and list-based tendencies to direct attention toward or away from word reading. PMID- 26860711 TI - Natural fast speech is perceived as faster than linearly time-compressed speech. AB - Listeners compensate for variation in speaking rate: In a fast context, a given sound is interpreted as longer than in a slow context. Experimental rate manipulations have been achieved either through linear compression or by using natural fast speech. However, in natural fast speech, segments are subject to processes such as reduction or deletion. If speaking rate is then defined as the number of segments per unit time, the question arises as to what impact such processes have on listeners' normalization for speaking rate. The present study tested the effect of sentence duration and fast-speech processes on rate normalization for a German vowel duration contrast. Results showed that a naturally produced short sentence containing segmental reductions and deletions led to the most "long" vowel responses whereas the long sentence with clearly articulated segments led to the fewest. This suggests that speaking rate is not merely calculated as the number of segments realized per unit time. Rather, listeners associate properties of natural fast speech with a higher speaking rate. This contrasts with earlier results and a second experiment in which perceived speaking rate was measured in an explicit task. Models of speech comprehension are evaluated with regard to the present findings. PMID- 26860712 TI - Age matters: The effect of onset age of video game play on task-switching abilities. AB - Although prior research suggests that playing video games can improve cognitive abilities, recent empirical studies cast doubt on such findings (Unsworth et al., 2015). To reconcile these inconsistent findings, we focused on the link between video games and task switching. Furthermore, we conceptualized video-game expertise as the onset age of active video-game play rather than the frequency of recent gameplay, as it captures both how long a person has played video games and whether the individual began playing during periods of high cognitive plasticity. We found that the age of active onset better predicted switch and mixing costs than did frequency of recent gameplay; specifically, players who commenced playing video games at an earlier age reaped greater benefits in terms of task switching than did those who started at a later age. Moreover, improving switch costs required a more extensive period of video-game experience than did mixing costs; this finding suggests that certain cognitive abilities benefit from different amounts of video game experience. PMID- 26860714 TI - X-ray Reciprocal Space Mapping of Graded Al x Ga1 - x N Films and Nanowires. AB - The depth distribution of strain and composition in graded Al x Ga1 - x N films and nanowires (NWs) are studied theoretically using the kinematical theory of X ray diffraction. By calculating [Formula: see text] reciprocal space maps (RSMs), we demonstrate significant differences in the intensity distributions from graded Al x Ga1 - x N films and NWs. We attribute these differences to relaxation of the substrate-induced strain on the NWs free side walls. Finally, we demonstrate that the developed X-ray reciprocal space map model allows for reliable depth profiles of strain and Al composition determination in both Al x Ga1 - x N films and NWs. PMID- 26860715 TI - Ultrafine-Grained Structure of Fe-Ni-C Austenitic Alloy Formed by Phase Hardening. AB - The X-ray and magnetometry methods were used to study alpha-gamma transformation mechanisms on heating quenched Fe-22.7 wt.% Ni-0.58 wt.% S alloy. Variation of heating rate within 0.03-80 K/min allowed one to switch from diffusive to non diffusive mechanism of the alpha-gamma transformation. Heating up primary austenitic single crystal specimen at a rate of less than 1.0-0.5 K/min has led to formation of aggregate of grains with different orientation and chemical composition in the reverted austenite. Significant fraction of these grains was determined to have sizes within nanoscale range. PMID- 26860717 TI - The Provision of Interventional Radiology Services in Europe: CIRSE Recommendations. AB - Interventional Radiology (IR) is an essential part of modern medicine, delivering minimally invasive patient-focused care, which has been proven to be safe and effective in both elective and emergency settings. The aim of this document is to outline the core requirements and standards for the provision of Interventional Radiological services, including training, certification, manpower, and accreditation. The ultimate challenge will be the adoption of these recommendations by different countries and health economies around the world, in turn ensuring equal access to IR treatments for all patients, the appropriate distribution of resources for IR service provision as well as the continued development of safe and high-quality IR services in Europe and beyond. PMID- 26860716 TI - Percutaneous Thermal Ablation of Breast Cancer Metastases in Oligometastatic Patients. AB - OBJECTIVE: To evaluate prognostic factors associated with local control and disease-free-survival (DFS) of oligometastatic breast cancer patients treated by percutaneous thermal ablation (PTA). MATERIALS AND METHODS: Seventy-nine consecutive patients (54.5 +/- 11.2 years old) with 114 breast cancer metastases (28.9 +/- 16.1 mm in diameter), involving the lungs, the liver, and/or the bone, were treated using PTA with a curative intent. The goal was to achieve a complete remission in association with systemic chemotherapy and hormonal therapy. We retrospectively evaluated the prognostic factors associated with 1- and 2-year local control and the 1- and 2-year DFS rates. RESULTS: The 1- and 2-year local control rates were 83.0 and 76.1 %, respectively. Tumor burden was associated with a poorer outcome for local control after PTA (HR 1.027 by additional millimeter, p = 0.026; >4 cm HR 3.90). The 1- and 2-year DFS rates were 54.2 and 30.4 %, respectively. In multivariate analysis, triple-negative histological subtype and increased size of treated metastases were associated with a poorer DFS (HR 2.22; 95 % CI [1.13-4.36]; p = 0.02 and HR 2.43; 95 % CI [1.22-4.82]; p = 0.011, respectively). CONCLUSION: PTA is effective for local control of breast cancer oligometastases. Tumor burden >4 cm and triple-negative histological subtype are associated with a poorer outcome. PMID- 26860719 TI - [Neuropsychological study in patients with Parkinson's disease: the effects of deep brain stimulation]. AB - INTRODUCTION: Parkinson's disease (PD) is a disorder whose clinical manifestations are observed in the motor and neuropsychological domain and have an impact on the patient's quality of life. Several scientific studies evidence the effectiveness of deep brain stimulation as treatment for the motor symptoms, but further research is required on the neuropsychological symptoms. AIM: To analyse the existence of significant differences in neuropsychological processes, such as attention, memory, language, visuoperception and the executive functions in patients with PD prior to and following deep brain stimulation. PATIENTS AND METHODS: Our sample consisted of 20 patients of both sexes, aged 50-70 years, with PD, who were treated by healthcare service providers in Medellin. These subjects were administered the Continuous Performance Test and the Trail Making Test in order to assess attention, the Rey Complex Figure and Ardila memory tests to evaluate memory, the Boston and verbal fluency tests to assess language, the Rey Complex Figure Copy test for visuoperception, and the Wisconsin Card Sorting Test to appraise the executive functions. RESULTS: There are significant differences between the scores before and after deep brain stimulation in patients with PD on attention and memory. CONCLUSIONS: Knowledge of these findings is relevant for the neuropsychological therapy of patients with PD. PMID- 26860718 TI - [Prognosis of non-symptomatic epilepsy in relation to their age of onset, monitored at a neuropediatric section of regional reference over a period of three years]. AB - AIM: To analyze the factors involved in the prognosis of non-symptomatic epilepsy (idiopathic and cryptogenic) in relation to their age of onset, monitored at a regional section of Neuropediatry reference over a period of three years. PATIENTS AND METHODS: Patients with diagnosis of non-symptomatic epilepsy supervised from January 1, 2008 to December 31, 2010, collecting epidemiological, clinical, complementary examinations and developmental data. RESULTS: Of the 4595 children attended during the period, the diagnosis of epilepsy was established in 605 (13.17%): 156 (25.79%) idiopathic epilepsies and 172 (28.43%) cryptogenic epilepsies. 15.7% of cryptogenic epilepsies and 14.1% of idiopathic epilepsies are refractory to treatment. Some epileptic syndromes, such as reflex epilepsies, Dravet syndrome, Ohtahara syndrome or Lennox-Gastaut syndrome, have higher rates of drug resistance. 84.62% of idiopathic epilepsies and 79.77% of cryptogenic epilepsies present no other associated neurological disorder. CONCLUSIONS: A useful classification would be etiological, with two groups: a large group with established etiology or very likely genetic syndromes and another with no established cause. The age of onset of epilepsy in each etiological group adds prognostic orientation. Prognosis of epilepsy is worsened by refractoriness and associated neurodevelopmental disorders, and are generally worse at an earlier onset and in certain etiologies. PMID- 26860720 TI - [Identification of the factors conditioning times and indicators of quality in the intrahospital care of acute stroke]. AB - INTRODUCTION: Stroke is a serious but potentially reversible entity. Reducing the time of care in the acute phase is essential to limit morbidity and mortality. The evaluation of the performances in stroke care is essential because it allows identify opportunities for improvement. AIM: To understand and analyze the determinants of the delay in the time of hospital care for the subsequent implementation of a cycle of improvement. PATIENTS AND METHODS: Retrospective study of patients with acute ischemic stroke treated with intravenous thrombolysis (IVT) and/or intra-arterial mechanical thrombectomy (IAMT) in a tertiary hospital between 2009-2014. In-hospital times, quality indicators and associated factors were analyzed. RESULTS: 337 patients with acute ischemic stroke were treated with IVT (66.2%) and/or IAMT (54.1%). In-hospital times (95% confidence interval): door-to-needle time, 75.88 min (71.67-80.16 min); door-to imaging, 43.27 min (40.17-46.37 min), imaging-to-needle, 38.01 min (34.08-41.93 min); IVT-IAMT time, 127.44 min (108.7-146.18 min); door-to-groin puncture, 155.22 min (140.03-170.40 min). 36.6% treated in less than 60 min, neuroimaging in less than 25 min in 19.9% and IVT-IAMT time in less than 90 minutes in 28.8%. Age, onset-to-door time, non-ambulance transport and the learning period were identified as determinants. CONCLUSIONS: Knowledge of the current situation of the times and quality indicators and their determinants are essential to provide the motivation to start an initiative to improve the quality of care in patients with acute stroke. PMID- 26860721 TI - [Phenotypic variations in Aicardi-Goutieres syndrome caused by RNASEH2B gene mutations: report of two new cases]. AB - INTRODUCTION: Aicardi-Goutieres syndrome is a rare immune disorder due to mutations in seven different genes that encode proteins called TREX1, ribonuclease H2 complex, SAMHD1, ADAR and IDIH1 (MDA5), which are involved in acid nucleic metabolism. Two cases are described in detail below caused by RNASEH2B gene mutation, one of which displays a mutation no described to date. CASE REPORTS: Case 1: male consulting because from 5-month-old shows loss of maturity items acquired until then, coming with several fever episodes. Case 2: a 4-month-old boy showing since 2-month-old great irritability and oral-feeding trouble with severe psychomotor impairment. In both cases it was found an increase of pterines in the cerebrospinal fluid, mainly neopterine, with calcifications in the basal ganglia. The diagnosis was proved by sequencing RNASEH2B gene, founding in case 2 a new mutation not described previously. CONCLUSIONS: The reported cases belong to the description already done by Aicardi Goutieres, it should be noticed this syndrome in a patient with a subacute encephalopathy of debut in the first year of life, dystonia/spasticity in variable degree and important affectation/regression of psychomotor development, particularly in those with increase of pterines (neopterine) in the cerebrospinal fluid and calcifications in the basal ganglia. PMID- 26860722 TI - [Cognitive and emotional alterations in chronic insomnia]. AB - INTRODUCTION: Little is known about the cognitive and emotional alterations associated with chronic insomnia. DEVELOPMENT: After reviewing the aetiology and pathophysiology of chronic insomnia, taking into account the patient's vulnerability and its inheritability, this study reports on the knowledge currently held about the cognitive deficits and emotional alterations observed in patients with chronic insomnia. CONCLUSIONS: Most aetiological models include factors that predispose an individual to insomnia, as well as precipitating and maintaining it. Predisposing factors can be of a biological or psychosocial nature. One predisposing factor that plays an important role is the vulnerability to insomnia, which is related to a non-adaptive way of coping with stress (focused on the emotion rather than on the problem) and the internalisation of negative emotions, which favours a state of physiological, cognitive and emotional hyperactivation that disrupts sleep and may lead to insomnia. This vulnerability is largely hereditary. Two phenotypes, based on the objective duration of sleep, have been described, the difference between them being the severity of the disorder. Insomniacs with an objective sleep time below six hours present significant cognitive deficits. These become manifest in tasks that require a large number of cognitive resources, complex attention tasks, changes in the focus of attention, the process of consolidation of memory during sleep, and working memory. These data suggest the existence of a prefrontal dysfunction. Comorbidity between insomnia and anxiety-depression is high. The anxiety depression triggered by the internalisation of emotions predisposes the individual to insomnia and this, in turn, intensifies the depression. PMID- 26860723 TI - [Spanish neuroscience in times of Don Quixote]. AB - INTRODUCTION: Miguel de Cervantes Saavedra published his immortal work Don Quixote of La Mancha in a time of crisis and decadence in Spain that occurred during the transition between the 16th and 17th centuries. AIMS: In 2016 we commemorate the fourth centenary of the death of our distinguished man of letters, and thus in this article we analyse the status of Hispanic neuroscience, both in the Quixote itself and in other works by the most significant contemporary writers of that time. DEVELOPMENT: Despite the adverse historical circumstances, the shift from the Renaissance to the Baroque periods, in the Crown of Castile, was a flourishing period for literature (Spanish Golden Age) and other Hispanic arts (painting, sculpture, architecture and music), as well as bearing witness to a prodigious creativity in the field of neuroscience, including the field of natural philosophy. In his book Antoniana Margarita the physician Gomez Pereira laid the foundations for brain mechanism and the concept of conditioned reflexes several decades ahead of his time. The apothecary Miguel Sabuco also anticipated the concept of neurotransmission centuries ahead of his time in his New Philosophy. The physician Juan Huarte de San Juan was the founder of neuropsychology and experimental psychology, and his Examination of Men's Wits has been one of the most influential and widely translated scientific texts of all times. Its concepts are clearly reflected in Cervantes' Quixote. CONCLUSION: This analysis of Cervantes' work within the cultural setting of the book is intended as a homage to the immortal figure of our 'Prince of Wits' in the fourth centenary of his death. PMID- 26860724 TI - [Bilateral cortical occipital infarction secondary to hydrocephalus due to a colloid cyst in the third ventricle]. PMID- 26860725 TI - [Assessment of 'neurophobia' or 'neurological illiteracy' as cause of increased assistance in child neurology]. PMID- 26860726 TI - Gonadal status in long-term male survivors of childhood cancer. AB - PURPOSE: To evaluate the prevalence of gonadal dysfunction and the associated risk factors in a cohort of male childhood cancer survivors (CCS). METHODS: Gonadal function was evaluated measuring FSH, LH, inhibin B and total testosterone levels. Patients with total testosterone <3 ng/dl were considered to have hypogonadism. Patients with FSH >10 UI/l and inhibin B <100 pg/ml were considered to have spermatogenesis damage (SD). To assess the impact of risk factors, we estimated crude and adjusted OR performing logistic regression models. RESULTS: One hundred and ninety-nine male CCS were enrolled; the median follow-up time was 14.01 years. SD was diagnosed in 68 patients, 16 CCS had primary hypogonadism, and 13 had central hypogonadism. The prevalence of gonadal dysfunction (SD or primary hypogonadism) was 45 %, similar in the three considered periods of pediatric cancer diagnosis (1985-1989, 1990-1999, >2000). The adjusted risk of gonadal dysfunction was higher in patients treated with radiotherapy (OR = 8.72; 95 % CI 3.94-19.30) and in those exposed to both alkylating and platinum-derived agents (OR = 9.22; 95 % CI 2.17-39.23). Sarcomas were the cancer diagnosis associated with the higher risk of gonadal dysfunction (OR = 3.69; 95 % CI 1.11-12.22). An extremely high rate of gonadal dysfunction was detected in patients who underwent hematopoietic stem cell transplantation and/or total body irradiation. CONCLUSIONS: Gonadal dysfunction still remains a significant late effect of anticancer therapies; thus, it is mandatory to inform patients (and parents) about this risk, and semen cryopreservation should be offered to all boys who are able to produce semen. PMID- 26860731 TI - Tongue entrapment within the lid of a plastic bottle. PMID- 26860730 TI - A multi-institutional, propensity-score-matched comparison of post-operative outcomes between general anesthesia and monitored anesthesia care with intravenous sedation in umbilical hernia repair. AB - PURPOSE: Monitored anesthesia care with intravenous sedation (MAC/IV), recently proposed as a good choice for hernia repair, has faster recovery and better patient satisfaction than general anesthesia; however the possibility of oversedation and respiratory distress is a widespread concern. There is a paucity of the literature examining umbilical hernia repairs (UHR) and optimal anesthesia choice, despite its importance in determining clinical outcomes. METHODS: A retrospective analysis of anesthesia type in UHR was performed in the National Surgical Quality Improvement Program 2005-2013 database. General anesthesia and MAC/IV groups were propensity-score-matched (PSM) to reduce treatment selection bias. Surgical complications, medical complications, and post-operative hospital stays exceeding 1 day were the primary outcomes of interest. Pre-operative characteristics and post-operative outcomes were compared between the two anesthesia groups using univariate and multivariate statistics. RESULTS: PSM removed all observed differences between the two groups (p > 0.05 for all tracked pre-operative characteristics). MAC/IV cases required fewer post-operative hospital stays exceeding 1 day (3.5 vs 6.3 %, p < 0.001). Univariate analysis showed that overall complication rate did not differ (1.7 vs 1.8 %, p = 0.569), however MAC/IV cases resulted in fewer incidences of septic shock (<0.1 vs 0.1 %, p = 0.016). After multivariate logistic regression, MAC/IV was revealed to yield significantly lower chances of overall medical complications (OR = 0.654, p = 0.046). CONCLUSION AND RELEVANCE: UHR under MAC/IV causes fewer medical complications and reduces post-operative hospital stays compared to general anesthesia. The implications for surgeons and patients are broad, including improved surgical safety, cost-effective care, and patient satisfaction. PMID- 26860734 TI - Cannabis use and symptoms of anxiety in adolescence and the moderating effect of the serotonin transporter gene. AB - There is substantial evidence for the assumption that particularly heavy cannabis usett is associated with a variety of psychopathologic conditions. Little is known about the relationship between cannabis and anxiety. Prior studies have concluded that cannabis use alone is not sufficient for the development of long term anxiety, and it has been suggested that cannabis is simply a risk factor that operates in conjunction with other risk factors. One such risk factor may be an individuals' genetic vulnerability. The present study examines the relationship between cannabis use and symptoms of anxiety by taking a developmental molecular-genetic perspective with a focus on a polymorphism involved in the regulation of serotonin. Specifically, we concentrated on changes in cannabis use and symptoms of anxiety over time and differences herein for individuals with and without the short allele of the 5-HTTLPR genotype. Data were from 1424 adolescents over a period of 5 years. We used different statistical analyses to test co-development of cannabis use and symptoms of anxiety throughout adolescence and the possible role of the 5-HTTLPR genotype in this process. Results from different analyses showed that cannabis use is associated with an increase in symptoms of anxiety, but only in carriers of the short allele of the 5-HTTLPR genotype, not in non-carriers. The findings of the present study show first evidence that the links between cannabis use and symptoms of anxiety are conditional on the individuals' genetic make-up. PMID- 26860728 TI - Who Should Transition? Defining a Target Population of Youth with Depression and Anxiety That Will Require Adult Mental Health Care. AB - The process of transitioning youth from child to adult mental health services is poorly managed, and many adolescents disengage from services during transfer. The waxing and waning of symptoms over time means that some youth who are asymptomatic prior to transfer (15-17 years) will be at high risk for recurrence during the transition period. There are no clear, evidence-based guidelines about who should transfer to adult care. Objectives were to propose: (1) criteria to define anxious or depressed youth (16-21 years) that should transfer and (2) levels of service needed in young adulthood. Natural history of psychopathology and treatment response for depression and anxiety was reviewed. Risk factors for recurrence and persistence, such as initial severity, comorbidity, and family functioning, can help to identify youth requiring transfer. Few controlled treatment studies have examined predictors of long-term course. Recommendations for follow-up care and ongoing monitoring during young adulthood are discussed. PMID- 26860732 TI - Luciferase NanoLuc as a reporter for gene expression and protein levels in Saccharomyces cerevisiae. AB - Reporter proteins are essential tools in the study of biological processes and are employed to monitor changes in gene expression and protein levels. Luciferases are reporter proteins that enable rapid and highly sensitive detection with an outstanding dynamic range. Here we evaluated the usefulness of the 19 kDa luciferase NanoLuc (Nluc), derived from the deep sea shrimp Oplophorus gracilirostris, as a reporter protein in yeast. Cassettes with codon-optimized genes expressing yeast Nluc (yNluc) or its destabilized derivative yNlucPEST have been assembled in the context of the dominant drug resistance marker kanMX. The reporter proteins do not impair the growth of yeast cells and exhibit half-lives of 40 and 5 min, respectively. The commercial substrate Nano-Glo(r) is compatible with detection of yNluc bioluminescence in < 50 cells. Using the unstable yNlucPEST to report on the rapid and transient expression of a heat-shock promoter (PCYC1-HSE ), we found a close match between the intensity of the bioluminescent signal and mRNA levels during both induction and decay. We demonstrated that the bioluminescence of yNluc fused to the C-terminus of a temperature-sensitive protein reports on its protein levels. In conclusion, yNluc and yNlucPEST are valuable new reporter proteins suitable for experiments with yeast using standard commercial substrate. (c) 2016 The Authors. Yeast published by John Wiley & Sons Ltd. PMID- 26860727 TI - Cell therapy centered on IL-1Ra is neuroprotective in experimental stroke. AB - Cell-based therapies are emerging as new promising treatments in stroke. However, their functional mechanism and therapeutic potential during early infarct maturation has so far received little attention. Here, we asked if cell-based delivery of the interleukin-1 receptor antagonist (IL-1Ra), a known neuroprotectant in stroke, can promote neuroprotection, by modulating the detrimental inflammatory response in the tissue at risk. We show by the use of IL 1Ra-overexpressing and IL-1Ra-deficient mice that IL-1Ra is neuroprotective in stroke. Characterization of the cellular and spatiotemporal production of IL-1Ra and IL-1alpha/beta identifies microglia, not infiltrating leukocytes, as the major sources of IL-1Ra after experimental stroke, and shows IL-1Ra and IL-1beta to be produced by segregated subsets of microglia with a small proportion of these cells co-expressing IL-1alpha. Reconstitution of whole body irradiated mice with IL-1Ra-producing bone marrow cells is associated with neuroprotection and recruitment of IL-1Ra-producing leukocytes after stroke. Neuroprotection is also achieved by therapeutic injection of IL-1Ra-producing bone marrow cells 30 min after stroke onset, additionally improving the functional outcome in two different stroke models. The IL-1Ra-producing bone marrow cells increase the number of IL-1Ra-producing microglia, reduce the availability of IL-1beta, and modulate mitogen-activated protein kinase (MAPK) signaling in the ischemic cortex. The importance of these results is underlined by demonstration of IL-1Ra producing cells in the human cortex early after ischemic stroke. Taken together, our results attribute distinct neuroprotective or neurotoxic functions to segregated subsets of microglia and suggest that treatment strategies increasing the production of IL-1Ra by infiltrating leukocytes or microglia may also be neuroprotective if applied early after stroke onset in patients. PMID- 26860735 TI - Antibacterial and antifungal activities of 2,3-pyrrolidinedione derivatives against oral pathogens. AB - Among the novel approaches applied to antimicrobial drug development, natural product-inspired synthesis plays a major role, by providing biologically validated starting points. Tetramic acids, a class of natural products containing a 2,4-pyrrolidinedione ring system, have attracted considerable attention for their antibacterial, antiviral, antifungal and anticancer activities. On the contrary, compounds with a 2,3-pyrrolidinedione skeleton have been considerably less investigated. In this work, we established chemical routes to the substituted 2,3-pyrrolidinedione core, which enabled the introduction of a wide range of diversity. In the perspective of a potential application for oral healthcare, a number of analogues with various substituents on the 2,3 pyrrolidinedione core were investigated for their antimicrobial and antifungal activities. The most promising compound showed a significant antimicrobial activity on Streptococcus mutans and Candida albicans, comparable to that of chlorhexidine, the gold standard in oral healthcare. PMID- 26860733 TI - Coexistence of splenic hemangioma and vascular malformation of the vertebrae. AB - BACKGROUND: Cavernous hemangioma is an encapsulated mass of dilated, endothelial lined vascular channels filled with slowly flowing blood. Cavernous hemangioma of the spleen is a rare condition with less than 100 reports so far. Hemangioma of the vertebral is a benign vascular legion around one or two vertebrae. These are usually asymptomatic and discovered incidentally. In this study we reported an extreme rare case of splenic hemangioma coexistence with vascular malformation of the vertebrae. To our knowledge this is the first report of coexistence of splenic hemangioma and hemangioma of the vertebra. CASE PRESENTATION: A 20-year old iranian male with splenomegaly, abdominal pain, diarrhea and pancytopenia who was first highly suspicious for malignancy referred to our center for evaluation of the diagnostic workup. After full examination we detected a very rare case with a giant, solitary cavernous hemangioma of the spleen and multiple hemangiomas in his vertebrae. Histopathology of the spleen showed a large cavernous hemangioma occupying almost the entire spleen with large areas of infarction necrosis with multiple hemangiomas of the vertebrae. CONCLUSION: It is extremely rare to have a splenic hemangioma concurrent with vertebra hemangioma and this is clinically very important to consider splenic hemangioma in differential diagnosis of splenomegaly for a better therapeutic management in related patients. PMID- 26860729 TI - Methods of abdominal wall expansion for repair of incisional herniae: a systematic review. AB - AIM: To systematically review the available literature regarding methods for abdominal wall expansion and compare the outcome of primary fascial closure rates. METHODS: A systematic search of Pubmed and Embase databases was conducted using the search terms "Abdominal wall hernia", "ventral hernia", "midline hernia", "Botulinum toxin", "botox", "dysport", "progressive preoperative pneumoperitoneum", and "tissue expanders". Study quality was assessed using the Methodological Index for Non-Randomised Studies. RESULTS: 21 of the 105 studies identified met the inclusion criteria. Progressive preoperative pneumoperitoneum (PPP) was performed in 269 patients across 15 studies with primary fascial closure being achieved in 226 (84%). 16 patients had a recurrence (7.2%) and the complication rate was 12% with 2 reported mortalities. There were 4 studies with 14 patients in total undergoing abdominal wall expansion using tissue expanders with a fascial closure rate of 92.9% (n = 13). A recurrence rate of 10.0% (n = 1) was reported with 1 complication and no mortalities. Follow up ranged from 3 to 36 months across the studies. There were 2 studies reporting the use of botulinum toxin with 29 patients in total. A primary fascial closure rate of 100% (n = 29) was demonstrated although a combination of techniques including component separation and Rives-Stoppa repair were used. There were no reported complications related to the use of Botulinum Toxin. However, the short-term follow up in many cases and the lack of routine radiological assessment for recurrence suggests that the recurrence rate has been underestimated. CONCLUSIONS: PPP, tissue expanders and Botulinum toxin are safe and feasible methods for abdominal wall expansion prior to incisional hernia repair. In combination with existing techniques for repair, these methods may help provide the crucial extra tissue mobility required to achieve primary closure. PMID- 26860736 TI - Synthesis of benzofuran derivatives as selective inhibitors of tissue-nonspecific alkaline phosphatase: effects on cell toxicity and osteoblast-induced mineralization. AB - Tissue-nonspecific alkaline phosphatase (TNAP) by hydrolyzing pyrophosphate, an inhibitor of apatite formation, promotes extracellular matrix calcification during bone formation and growth, as well as during ectopic calcification under pathological conditions. TNAP is a target for the treatment of soft tissue pathological ossification. We synthesized a series of benzofuran derivatives. Among these, SMA14, displayed TNAP activity better than levamisole. SMA14 was found to be not toxic at doses of up to 40MUM in osteoblast-like Saos-2 cells and primary osteoblasts. As probed by Alizarin Red staining, this compound inhibited mineral formation in murine primary osteoblast and in osteoblast-like Saos-2 cells. PMID- 26860739 TI - Rasmussen's legacy: A paradigm change in engineering for safety. AB - This paper describes three applications of Rasmussen's idea to systems engineering practice. The first is the application of the abstraction hierarchy to engineering specifications, particularly requirements specification. The second is the use of Rasmussen's ideas in safety modeling and analysis to create a new, more powerful type of accident causation model that extends traditional models to better handle human-operated, software-intensive, sociotechnical systems. Because this new model has a formal, mathematical foundation built on systems theory (as was Rasmussen's original model), new modeling and analysis tools become possible. The third application is to engineering hazard analysis. Engineers have traditionally either omitted human from consideration in system hazard analysis or have treated them rather superficially, for example, that they behave randomly. Applying Rasmussen's model of human error to a powerful new hazard analysis technique allows human behavior to be included in engineering hazard analysis. PMID- 26860738 TI - Erratum to: Bone healing after low-level laser application in extraction sockets grafted with allograft material and covered with a resorbable collagen dressing: a pilot histological evaluation. PMID- 26860740 TI - Holistic sustainable development: Floor-layers and micro-enterprises. AB - Attracting and retaining workers is important to ensuring the sustainability of floor laying businesses, which are for the most part micro-enterprises (MiE). The aim of this paper is to shed light on the challenges MiE face in OHS implementation in the context of sustainable development. Participative ergonomics and user-centred design approaches were used. The material collected was reviewed to better understand the floor layers' viewpoints on sustainability. The solutions that were retained and the challenges encountered to make material handling and physical work easier and to develop training and a website are presented. The importance of OHS as a sustainability factor, its structuring effect, what distinguishes MiE from small businesses and possible strategies for workings with them are also discussed. PMID- 26860741 TI - Digital Gaming for Improving the Functioning of People With Traumatic Brain Injury: Protocol of a Feasibility Study. AB - BACKGROUND: Traumatic brain injury (TBI) is a critical public health problem. The recovery process for people with TBI is typically slow and dependent on complex and intensive assisted rehabilitation programs. OBJECTIVE: To evaluate the effects and feasibility of digital games for cognitive functioning and general well-being among people with traumatic brain injury. METHODS: This is a single site feasibility study conducted in Finland, which uses a pragmatic, randomized controlled trial with three arms, and will recruit patients from the Turku University Hospital, Division of Clinical Neurosciences in Finland. Participants must meet the following inclusion criteria: (1) a Finnish speaking adult, aged 18 65 years; (2) diagnosed with a traumatic brain injury (diagnostic criteria ICD 10, S06.X, T90.5) in the University Hospital; (3) access to a TV, a computer, and the Internet at home; (4) not an active digital gamer (5 hours or less a week); (5) willing to participate in the study. Participants must have been discharged from the neurologic treatment period for traumatic brain injury for over 12 months before the commencement of the trial, and they may not have actively participated in cognitive rehabilitation during the 3 months prior to the trial. Written informed consent will be mandatory for acceptance into the trial. Exclusion criteria are as follows: (1) sensory, cognitive, or physical impairment (eg, severe cognitive impairment); (2) a deficiency restricting the use of computers or computer game control system unaided (eg, impairment in vision, severe astigmatism, hemiplegia, disorder in visuospatial perception, dysfunction of the central vestibular system); (3) apathy identified in previous neuropsychological evaluations; (4) diagnosed severe mental disorders (eg, schizophrenia or severe depressive disorders to be identified in medical records as the secondary diagnosis). RESULTS: The preparatory phase for the study is fulfilled. Recruitment started in June 2015 and finished November 2015. Results will be reported in 2016. CONCLUSIONS: The specific outcomes such as primary outcome measures were selected because they are widely used psychological tests and thought to be sensitive to changes in the cognitive functions related to TBI. TRIAL REGISTRATION: Clinicaltrials.gov NCT02425527; https://clinicaltrials.gov/ct2/show/NCT02425527 (Archived by WebCite at http://www.webcitation.org/6esKI1uDH). PMID- 26860743 TI - The attitudes of medical students toward the importance of understanding classical Greek and Latin in the development of an anatomical and medical vocabulary. AB - Students on entering medical school are faced with acquiring new, and voluminous, anatomical and medical terminologies. A reason why acquiring these terminologies may be problematic relates to the fact that many terms are derived from classical Greek and Latin; languages nowadays that are rarely taught at school. It might also be supposed that the often reported reduction in exposure to anatomy, and time spent in the dissection room, impairs the students' knowledge and understanding of anatomical relationships, and thus further complicates the acquisition of the terminologies. To date, there have been no studies that have quantified the attitudes of medical students toward the importance of understanding classical Greek and Latin during their medical training. In order to assess these attitudes, this study was undertaken for the newly-recruited (First Year) medical students and for the Final Year medical students at Cardiff University. They were provided with a brief questionnaire that was devised in accordance with Thurstone and Chave (1951) principles and with ethical approval. One hundred and eighty First Year students and one hundred and nineteen Final Year students responded. Our initial hypothesis was that students throughout the medical curriculum have an unfavorable attitude toward the importance of classical Greek and Latin. This hypothesis was supported by the attitudes of the Final Year students but not by the First Year medical students. While we would still advocate that First Year medical students should acquire some understanding of and have some formal or informal instruction in, classical Greek and Latin as they pertain to medical terminologies, we acknowledge that Final Year students are likely to have become reasonably well-versed in the origins of medical terminologies without formal instruction. Clin. Anat. 29:696-701, 2016. (c) 2016 Wiley Periodicals, Inc. PMID- 26860742 TI - Sarilumab for the treatment of rheumatoid arthritis. AB - Simon Cooper has >18 years of global experience in the pharmaceutical industry. He joined Sanofi in July 2014 as the Vice President, Global Project Head. In his current position at Sanofi, Dr Cooper is responsible for the clinical development of sarilumab and the worldwide submission in rheumatoid arthritis. He joined Sanofi after serving as the Global Program Medical Director at Novartis since 2012. In this role, Dr Cooper acted as the clinical lead for secukinumab psoriasis submission. Prior to Novartis, Dr Cooper held various posts at Human Genome Sciences, USA, including Executive Director of Clinical Research, Senior Director of Clinical Research and Director of Clinical Research. During his tenure at Human Genome Sciences, USA, Dr Cooper was involved in the submission of belimumab leading to its approval for SLE, and was responsible for its subsequent clinical development program. Dr Cooper has also previously held positions at MedImmune Ltd, UK, Roche, Napp Pharmaceutical Research Ltd, Wyeth Research and Medeval Ltd. In these roles, his responsibilities ranged from medical oversight of clinical trials to medical support for commercial, medical affairs and business development. He received a Bachelor of Medicine and Bachelor of Surgery from University of Newcastle upon Tyne Medical School. PMID- 26860744 TI - Pharmaceutical Thermal Processing. PMID- 26860747 TI - [A baby with an unexplained skin rash]. AB - A 2-month-old infant presented with papules and pustules. Since the patient's mother and brother also had an unexplained--itchy--skin rash, it was thought that the skin rash was due to scabies. This diagnosis was confirmed by dermatoscopy and direct microscopic examination. PMID- 26860745 TI - Intrinsic differences between males and females determine sex-specific consequences of inbreeding. AB - BACKGROUND: Inbreeding increases homozygosity and exposes deleterious recessive alleles, generally decreasing the fitness of inbred individuals. Interestingly, males and females are usually affected differently by inbreeding, though the more vulnerable sex depends on the species and trait measured. RESULTS: We used the soil-dwelling nematode Caenorhabditis remanei to examine sex-specific inbreeding depression across nine lineages, five levels of inbreeding, and hundreds of thousands of progeny. Female nematodes consistently suffered greater fitness losses than their male counterparts, especially at high levels of inbreeding. CONCLUSIONS: These results suggest that females experience stronger selection on genes contributing to reproductive traits. Inbreeding depression in males may be further reduced by sex chromosome hemizygosity, which affects the dominance of some mutations, as well as by the absence of sexual selection. Determining the relative contributions of sex-specific expression, genes on the sex chromosomes, and the environment they are filtered through-including opportunities for sexual selection-may explain the frequent though inconsistent records of sex differences in inbreeding depression, along with their implications for conservation and the evolution of mating systems. PMID- 26860746 TI - Os odontoideum in wolcott-rallison syndrome: a case series of 4 patients. AB - Wolcott-Rallison Syndrome is the commonest cause of neonatal diabetes in consanguineous families. It is associated with liver dysfunction, epiphyseal dysplasia, and developmental delay. It is caused by mutations in eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3).We report 4 children with WRS and Os Odontoideum resulting in significant neurological compromise. This cervical spine abnormality has not previously been described in this syndrome. This additional evidence broadens the clinical spectrum of this syndrome and confirms the role of EIF2AK3 in skeletal development. Furthermore, Os Odontoideum needs to be actively screened for in WRS patients to prevent neurological and respiratory compromise. PMID- 26860748 TI - [Cutaneous ulcerating nodules after many years of immunotherapy]. AB - A 40-year-old female patient was referred to the department of Dermatology with subcutaneous nodules and ulcers years after starting with immunotherapy injections (Purethal) for hay fever. The skin reaction appeared to be due to aluminium hydroxide, which is used as an adjuvant to many injections and vaccins. Aluminium hydroxide can cause delayed granulomatous contact dermatitis or foreign body reactions. PMID- 26860749 TI - [Amyotrophic lateral sclerosis, a heterogeneous disorder]. AB - ALS is a disease characterized by the progressive loss of upper and lower motor neurons leading to weakness and spasticity. Diagnosis of ALS is based on exclusion. ALS and frontotemporal dementia (FTD) constitute the extremes of the spectrum of one disease. Many patients show signs of both ALS and FTD. ALS is a heterogeneous disease in which multiple genetic factors contribute. More than 20 genes are known to play a role in ALS pathogenesis. In approximately 5-10% of cases the disease is familial with autosomal dominant inheritance. There is no curative treatment for ALS. The treatment of ALS patients is symptomatic and is focused on achieving a high level of quality of life. New insights into the genetic fundamentals of ALS offer hope for new therapies. Gene-targeted treatment strategies using antisense oligonucleotides are a promising development. PMID- 26860750 TI - [A neonate with blisters on his upper legs]. AB - A 10-days-old male neonate presented with multiple bullae, mostly in the diaper region, without signs of illness. We diagnosed this condition as neonatal bullous impetigo and treated the patient orally with flucloxacillin. Bullous impetigo is caused by Staphylococcus aureus toxins that break down intercellular proteins. PMID- 26860751 TI - [When is laparoscopic surgery safe in cancer?]. AB - In the Netherlands more than 75% of colorectal cancers are operated on laparoscopically. Randomised controlled trials and population-based studies, corrected for case mix, provide overwhelming evidence that the laparoscopic approach is superior to open surgery in the short term, and that long-term oncological outcomes are not inferior to those of open surgery. Therefore, the question should be rephrased. As laparoscopy should be considered the new gold standard, who still needs open surgery? Probably only the unhappy few with locally advanced tumours and adhesions. PMID- 26860752 TI - [Antimicrobial resistance: is it really all going wrong now?]. AB - In November 2015, plasmid-mediated colistin resistance in Gram-negative bacteria was reported for the first time, and it was evident that this newly-identified resistance gene (mcr-1) was already prevalent in the animal and human reservoir in China. As well as massive media attention, there was also a massive scientific response. As of 22 January 2016, the interpretation of all the evidence is that the mcr-1 was already in existence in 2005 and is not bound to a single plasmid. Its presence has now been demonstrated on four continents and the gene seems widely prevalent in animal reservoirs across the globe, with a very low prevalence in collections of human isolates. Based on current findings there seems to be no reason to change clinical practices for Dutch patients. PMID- 26860753 TI - Neurofibromatosis type 1: Fundamental insights into cell signalling and cancer. AB - Neurofibromatosis type 1 (NF1) is an autosomal dominant tumour predisposition syndrome that is caused through loss of function mutations of a tumour suppressor gene called Neurofibromin 1. Therapeutic options are currently limited for NF1 associated tumours, where treatment is often restricted to complete surgical resection with clear margins. Herein, we discuss the multifunctional tumour suppressive role of neurofibromin, which is classically known as a GTPase activating protein (GAP) towards the RAS small GTPase. While neurofibromin inhibits proliferative growth through blockade of RAS-mediated signal transduction, neurofibromin should also be considered as a modulator of cell motility and cell adhesion. Through interfacing with the cytoskeleton and membrane structures, neurofibromin acts as a negative regulator of RHO/ROCK signalling pathways involved in cytoskeletal dynamics that are instrumental in proper neuronal development. In the context of cancer, the loss of normal function of neurofibromin via genetic mutation results in heightened cell proliferation and migration, predisposing NF1 patients to cancer. Malignant Peripheral Nerve Sheath Tumours (MPNSTs) can develop from benign neurofibromas and are the main cause of death amongst NF1 patients. Through recent research on MPNSTs, we have gained insight into the key molecular events that drive their malignancy. Advances regarding malignant drivers involved in cell migration, cell invasion and angiogenic signalling are discussed in this review, where these findings will likely influence future therapies for both NF1 and related sporadic cancers. PMID- 26860755 TI - Prepubertal castration-associated developmental changes in sigma-1 receptor gene expression levels regulate hippocampus area CA1 activity during adolescence. AB - The functional relevance of sigma-1 (sigma1 ) receptor expression in the rat hippocampal CA1 during adolescence (i.e., 35-60 days old) was explored. A selective antagonist for the sigma1 receptor subtype, BD-1047, was applied to study hippocampal long-term potentiation (LTP) and spatial learning performance. Changes in the expression of the sigma1 receptor subtype and its function were compared between castrated and sham-castrated rats. Castration reduced the magnitude of both field excitatory postsynaptic potential (fEPSP)-LTP and population spike (PS)-LTP at 35 days (d). BD-1047 decreased PS-LTP in sham castrated rats, whereas BD-1047 reversed the effect of castration on fEPSP-LTP at 35 d. In addition, BD1047 impaired spatial learning and augmented sigma1 receptor mRNA levels in castrated rats at 35 d. Surprisingly, neither castration nor BD1047 had an effect on fEPSP-LTP and PS-LTP, spatial learning ability or gene expression levels at 45 d. Castration had no effect on fEPSP-LTP but reduced PS LTP at 60 d. BD1047 increased the magnitude of fEPSP-LTP, but had no effect on PS LTP in castrated rats at 60 d. However, BD1047 reduced spatial learning ability, and sigma1 receptor mRNA levels were decreased in castrated rats at 60 d. This study shows that sigma1 receptors play a role in the regulation of both CA1 synaptic efficacy and spatial learning performance. The regulatory role of sigma1 receptors in activity-dependent CA1-LTP is locality- and age-dependent, whereas its role in spatial learning ability is only age-dependent. Prepubertal castration-associated changes in the expression and function of the sigma1 receptor during adolescence may play a developmental role in the regulation of hippocampal area CA1 activity and plasticity. (c) 2016 Wiley Periodicals, Inc. PMID- 26860756 TI - We Need a New Approach in Implementing and Achieving the Sustainable Development Goals. PMID- 26860757 TI - Introduction. PMID- 26860758 TI - Addressing Maternal and Newborn Health: A Leadership Perspective. AB - Globally, each year 289,000 mothers die in childbirth and three million infants die in the first four weeks of life. The shortcomings in maternal and newborn health are particularly devastating in low-resource countries. This qualitative study describes the experience of an international nongovernmental organization, Jhpiego, which has been implementing public health programs to address maternal and newborn health outcomes for more than 40 years. Themes emerged from interviews with leaders of offices in a variety of countries with unique challenges related to health systems, human resources and infrastructure. Results emphasized the importance of partnerships with governments and international agencies for long-term program impact, as well as the recruitment of local talent for improving health systems to address problems that are best understood by the people who live and work in these countries. The discussion of program successes and challenges may inform best practices for promoting the health and wellness of women and families around the world. PMID- 26860759 TI - Case Study: Clinical Governance as an Approach to Improve Maternal and Newborn Health in 22 Hospitals in Indonesia. AB - Clinical governance is a concept used to improve management, accountability and the provision of quality healthcare. An approach to strengthen clinical governance as a means to improve the quality of maternal and newborn care in Indonesia was developed by the Expanding Maternal and Neonatal Survival (EMAS) Program. This case study presents findings and lessons learned from EMAS program experience in 22 hospitals where peer-to-peer mentoring supported staff in strengthening clinical governance from 2012-2015. Efforts resulted in improved hospital preparedness and significantly increased the odds of facility-level coverage for three evidence-based maternal and newborn healthcare interventions. PMID- 26860760 TI - Case Study: A Rapid Rollout of Universal Maternal HAART Improves Outcomes among HIV-Positive Women and Their Infants in Kenya. AB - Globally, countries have made significant achievements in reducing rates of mother-to-child transmission (MTCT) of HIV. In Kenya, MTCT rates were most recently estimated at 8%, with 220,000 children under 15 years of age living with HIV. In 2013, the World Health Organization recommended highly active antiretroviral therapy (HAART) for all HIV-infected pregnant and lactating women. APHIAPLUSKAMILI supported rollout of a county-level, targeted, rapid scale-up of HAART in 152 high-volume facilities in Kenya. A review and comparison of data from these facilities in 2013 and 2014 revealed a significant increase in the proportion of women started on HAART and a reduction in MTCT. PMID- 26860754 TI - STAT3 in the systemic inflammation of cancer cachexia. AB - Weight loss is diagnostic of cachexia, a debilitating syndrome contributing mightily to morbidity and mortality in cancer. Most research has probed mechanisms leading to muscle atrophy and adipose wasting in cachexia; however cachexia is a truly systemic phenomenon. Presence of the tumor elicits an inflammatory response and profound metabolic derangements involving not only muscle and fat, but also the hypothalamus, liver, heart, blood, spleen and likely other organs. This global response is orchestrated in part through circulating cytokines that rise in conditions of cachexia. Exogenous Interleukin-6 (IL6) and related cytokines can induce most cachexia symptomatology, including muscle and fat wasting, the acute phase response and anemia, while IL-6 inhibition reduces muscle loss in cancer. Although mechanistic studies are ongoing, certain of these cachexia phenotypes have been causally linked to the cytokine-activated transcription factor, STAT3, including skeletal muscle wasting, cardiac dysfunction and hypothalamic inflammation. Correlative studies implicate STAT3 in fat wasting and the acute phase response in cancer cachexia. Parallel data in non cancer models and disease states suggest both pathological and protective functions for STAT3 in other organs during cachexia. STAT3 also contributes to cancer cachexia through enhancing tumorigenesis, metastasis and immune suppression, particularly in tumors associated with high prevalence of cachexia. This review examines the evidence linking STAT3 to multi-organ manifestations of cachexia and the potential and perils for targeting STAT3 to reduce cachexia and prolong survival in cancer patients. PMID- 26860761 TI - Case Study: Experience Applying and Tracking a Quality Improvement Approach for Maternal and Newborn Health Services in Sub-Saharan Africa. AB - The Standards-Based Management and Recognition (SBM-R((r))) approach to quality improvement was applied to maternal and newborn health services in Guinea, Mozambique, Nigeria and Zimbabwe. In every country, the quality of service delivery, as measured by clinical performance standards, improved following the intervention. The performance of evidence-based service delivery practices, as measured through service statistics, also increased and institutional rates of postpartum hemorrhage and very early neonatal deaths exhibited declining trends. Findings suggest that the effects of SBM-R reach beyond service delivery processes to health outputs and outcomes and demonstrate the potential returns of investing in quality improvement approaches. PMID- 26860762 TI - Case Study: Effects of a Media Campaign on Breastfeeding Behaviors in Sindh Province, Pakistan. AB - A 2013-2014 media campaign in Sindh Province, Pakistan, promoted healthy breastfeeding practices. According to data from annual household surveys, 26.7% of mothers saw one television spot and 19.4% saw another. The proportion of mothers who received breastfeeding information via television increased from 8.3% to 29.4% after the campaign (p<=0.05) and the percentage receiving information from doctors, mothers-in-law and relatives/friends nearly doubled (p<=0.05). However, no improvements in breastfeeding practices were reported. The experience in Sindh suggests that, in order to change breastfeeding practices, mass media interventions should be linked with other interventions, such as provider counseling, that involve influential family members in addition to mothers. PMID- 26860763 TI - Case Study: Primary Healthcare Clinical Placements during Nursing and Midwifery Education in Lesotho. AB - In Lesotho, primary healthcare is the main access point for health services. While nurses and midwives provide most of the care at this level, assessments of the clinical education programs have highlighted gaps in primary healthcare experiences for nursing and midwifery students. This case study examines placement of nursing and midwifery students in primary health clinics alongside preceptors. The placements provide students with varied clinical experience, better preparing them to practice in primary healthcare clinics. To date, more than 700 nursing and midwifery students have been placed in 40 rural health centres and 228 preceptors have been trained. The government is scaling up the program nationally. PMID- 26860764 TI - Case Study: The Role of eLearning in Midwifery Pre-Service Education in Ghana. AB - The issues and challenges of implementing eLearning in pre-service health education were explored through a pilot study conducted in six nurse-midwifery education programs in Ghana. Case-based, interactive computer mediated eLearning modules, targeted to basic emergency and obstetrical signal functions, were delivered both online and offline using a free-for-use eLearning platform, skoool HE((r)). Key success factors included broad stakeholder support, an established curriculum and student and tutor interest. Challenges included infrastructure limitations, large class sizes and added workloads for tutors and information technology staff. National scale up is planned. PMID- 26860765 TI - Factors Affecting Turnover Intention among Nurses in Ethiopia. AB - BACKGROUND: Reducing turnover is essential to address health worker shortages in the public sector and improve the quality of services. This study examines factors associated with Ethiopian nurses' intention to leave their jobs. METHODS: Survey respondents (a sample of 425 nurses at 122 facilities) rated the importance of 20 items in decisions to leave their jobs and reported whether they intended to leave their jobs in the next year. Descriptive and inferential statistical analyses were used to identify predictors of nurses' intentions to leave their jobs. RESULTS: Half (50.2%) the nurses said they intended to leave their jobs in the next year. A multivariate analysis identified three significant predictors of nurses' intention to leave their jobs: holding a university degree rather than a diploma (adjusted odds ratio (OR)=2.246, 95% confidence interval (CI)=1.212, 4.163; p<0.01), having worked fewer years in the public health system (adjusted OR=0.948, 95% CI=0.914, 0.982; p<0.01) and rating the importance of limited opportunities for professional development more highly (adjusted OR=1.398, 95% CI=1.056, 1.850; p<0.02). CONCLUSION: Interventions to increase the retention of nurses at public health facilities in Ethiopia should target young nurses who are completing their compulsory service obligation and nurses with a university degree. They should include both non-financial and financial incentives. PMID- 26860766 TI - Case Study: Using Task Analysis to Determine the Status of Education and Practice of Medical Licentiates for the Provision of Anesthesia in Zambia. AB - Task analysis methodology was used to identify gaps in the education and practice of Medical Licentiates, a cadre of primary care health providers in Zambia, related to the provision of anesthesia. Findings of the analysis indicate that Medical Licentiates who work in facilities where there are no fully qualified anesthesiologists or physicians often feel obligated to provide these services in order to save lives although they lack sufficient formal education or clinical practice opportunities. The government translated the findings into immediate modifications to the education, training and practice of anesthetic tasks by Medical Licentiates by developing an elective course within the pre-service education program and upgrading the certification of Medical Licentiates to a bachelor's degree. PMID- 26860767 TI - New method of neck surface electromyography for the evaluation of tongue-lifting activity. AB - Elevation of the posterior part of the tongue is important for normal deglutition and speech. The purpose of this study was to develop a new surface electromyography (EMG) method to non-invasively and objectively evaluate activity in the muscles that control lifting movement in the posterior tongue. Neck surface EMG (N-EMG) was recorded using differential surface electrodes placed on the neck, 1 cm posterior to the posterior border of the mylohyoid muscle on a line orthogonal to the lower border of the mandible. Experiment 1: Three healthy volunteers (three men, mean age 37.7 years) participated in an evaluation of detection method of the posterior tongue lifting up movement. EMG recordings from the masseter, temporalis and submental muscles and N-EMG revealed that i) N-EMG was not affected by masseter muscle EMG and ii) N-EMG activity was not observed during simple jaw opening and tongue protrusion, revealing the functional difference between submental surface EMG and N-EMG. Experiment 2: Seven healthy volunteers (six men and one woman, mean age 27.9 years) participated in a quantitative evaluation of muscle activity. Tongue-lifting tasks were perfor-med, exerting a prescribed force of 20, 50, 100 and 150 gf with visual feedback. For all subjects, a significant linear relationship was observed bet-ween the tongue lifting force and N-EMG activity (P < 0.01). These findings indicate that N-EMG can be used to quantify the force of posterior tongue lifting and could be useful to evaluate the effect of tongue rehabilitation in future studies. PMID- 26860768 TI - Suppressive Effects of Barley beta-Glucans with Different Molecular Weight on 3T3 L1 Adipocyte Differentiation. AB - In this study, 2 beta-glucans with different molecular weight were prepared and purified from hull-less barley bran. The aim was to evaluate their effects on the differentiation of 3T3-L1 pre-adipocytes. Results showed that barley beta-glucans inhibited the differentiation of 3T3-L1 pre-adipocytes induced by differentiation medium in a dose-dependent manner, the suppressive effect of high-molecular weight barley beta-glucans (552 kDa, BGH) was stronger (P < 0.05) than that of low-molecular-weight barley beta-glucan (32 kDa, BGL), evidenced by the significantly decrease (P < 0.05) of Oil-red O staining and intracellular triglyceride content in the mature adipocytes. Besides, gene expression analysis and Western Blot analysis revealed that both BGH and BGL inhibited the mRNA and protein levels of adipogenesis related transcription factors peroxisome proliferator-activated receptor gamma (PPARgamma) and CCAAT-enhancer-binding protein alpha (C/EBPalpha) which are principal regulators of adipogenesis. Furthermore, the mRNA and protein expression levels of PPARgamma target genes in adipose tissue including adipocyte fatty acid binding protein (ap2), lipoprotein lipase (LPL), uncoupling protein-2 (UCP-2), and glucose-transporter 4 (Glut4) in 3T3-L1 cells was also markedly downregulated (P < 0.05). These findings were anticipated to help develop barley beta-glucans based functional food for the management of obesity. PMID- 26860769 TI - Defective monocyte oxidative burst predicts infection in alcoholic hepatitis and is associated with reduced expression of NADPH oxidase. AB - OBJECTIVE: In order to explain the increased susceptibility to serious infection in alcoholic hepatitis, we evaluated monocyte phagocytosis, aberrations of associated signalling pathways and their reversibility, and whether phagocytic defects could predict subsequent infection. DESIGN: Monocytes were identified from blood samples of 42 patients with severe alcoholic hepatitis using monoclonal antibody to CD14. Phagocytosis and monocyte oxidative burst (MOB) were measured ex vivo using flow cytometry, luminometry and bacterial killing assays. Defects were related to the subsequent development of infection. Intracellular signalling pathways were investigated using western blotting and PCR. Interferon gamma (IFN-gamma) was evaluated for its therapeutic potential in reversing phagocytic defects. Paired longitudinal samples were used to evaluate the effect of in vivo prednisolone therapy. RESULTS: MOB, production of superoxide and bacterial killing in response to Escherichia coli were markedly impaired in patients with alcoholic hepatitis. Pretreatment MOB predicted development of infection within two weeks with sensitivity and specificity that were superior to available clinical markers. Accordingly, defective MOB was associated with death at 28 and 90 days. Expression of the gp91 phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase was reduced in patients with alcoholic hepatitis demonstrating defective MOB. Monocytes were refractory to IFN-gamma stimulation and showed high levels of a negative regulator of cytokine signalling, suppressor of cytokine signalling-1. MOB was unaffected by 7 days in vivo prednisolone therapy. CONCLUSIONS: Monocyte oxidative burst and bacterial killing is impaired in alcoholic hepatitis while bacterial uptake by phagocytosis is preserved. Defective MOB is associated with reduced expression of NADPH oxidase in these patients and predicts the development of infection and death. PMID- 26860772 TI - Limitations of Condensed Teaching Strategies to Develop Hand-Held Cardiac Ultrasonography Skills in Internal Medicine Residents. AB - Advances in ultrasonographic technology have allowed for hand-held cardiac ultrasonography (HHCU) units that fit into a physician's laboratory coat. Recently, studies to educate internal medicine residents have shown promise. The optimal duration and methodology for teaching HHCU skills has not been established. Over a 1-year period, internal medicine residents were recruited during their cardiology ward rotation into a single-centre nonblinded randomized trial. The 2 condensed teaching strategies were (1) a conventional ward-based program and (2) a technology-driven simulation-based strategy. Outcomes were evaluated by (1) an objective structured clinical examination (OSCE) to evaluate interpretation ability (assessing both type I and type II error rates) and (2) demonstration of HHCU skills graded by 2 level III echocardiographers. Twenty four internal medicine residents were randomized. After teaching, the conventional teaching group had a significant absolute increase in the ability to make a singular correct diagnosis (20%; P < 0.001). In the technology arm, making a singular correct diagnosis increased 24% from baseline (P = 0.001). Interpretation skill was not significantly different between groups. The false positive rate increased by an absolute 14% and 17% in the conventional and technology groups, respectively (P = 0.079 and P = 0.008). Our findings suggest that HHCU interpretation skills improve after either a conventional ward-based or a technology-driven approach. However, our study emphasizes the important limitations of both teaching programs, because we detected a trend toward an increase in the false-positive rate after both approaches. This suggests that a short duration of training may not be sufficient for HHCU to be performed in a safe manner. PMID- 26860770 TI - Interferon-microRNA signalling drives liver precancerous lesion formation and hepatocarcinogenesis. AB - OBJECTIVE: Precancerous lesion, a well-established histopathologically premalignant tissue with the highest risk for tumourigenesis, develops preferentially from activation of DNA damage checkpoint and persistent inflammation. However, little is known about the mechanisms by which precancerous lesions are initiated and their physiological significance. DESIGN: Laser capture microdissection was used to acquire matched normal liver, precancerous lesion and tumour tissues. miR-484(-/-), Ifnar1(-/-) and Tgfbr2(?hep) mice were employed to determine the critical role of the interferon (IFN)-microRNA pathway in precancerous lesion formation and tumourigenesis. RNA immunoprecipitation (RIP), pull-down and chromatin immunoprecipitation (ChIP) assays were applied to explore the underlying mechanisms. RESULTS: miR-484 is highly expressed in over 88% liver samples clinically. DEN-induced precancerous lesions and hepatocellular carcinoma were dramatically impaired in miR-484(-/-) mice. Mechanistically, ectopic expression of miR-484 initiates tumourigenesis and cell malignant transformation through synergistic activation of the transforming growth factor-beta/Gli and nuclear factor-kappaB/type I IFN pathways. Specific acetylation of H3K27 is indispensable for basal IFN-induced continuous transcription of miR-484 and cell transformation. Convincingly, formation of precancerous lesions were significantly attenuated in both Tgfbr2(?hep) and Ifnar1(-/-) mice. CONCLUSIONS: These findings demonstrate a new protumourigenic axis involving type I IFN microRNA signalling, providing a potential therapeutic strategy to manipulate or reverse liver precancerous lesions and tumourigenesis. PMID- 26860771 TI - Deletion of Men1 and somatostatin induces hypergastrinemia and gastric carcinoids. AB - BACKGROUND: Gastric carcinoids are slow growing neuroendocrine tumours arising from enterochromaffin-like (ECL) cells in the corpus of stomach. Although most of these tumours arise in the setting of gastric atrophy and hypergastrinemia, it is not understood what genetic background predisposes development of these ECL derived tumours. Moreover, diffuse microcarcinoids in the mucosa can lead to a field effect and limit successful endoscopic removal. OBJECTIVE: To define the genetic background that creates a permissive environment for gastric carcinoids using transgenic mouse lines. DESIGN: The multiple endocrine neoplasia 1 gene locus (Men1) was deleted using Cre recombinase expressed from the Villin promoter (Villin-Cre) and was placed on a somatostatin null genetic background. These transgenic mice received omeprazole-laced chow for 6 months. The direct effect of gastrin and the gastrin receptor antagonist YM022 on expression and phosphorylation of the cyclin inhibitor p27Kip1 was tested on the human human gastric adenocarcinoma cell line stably expressing CCKBR (AGSE) and mouse small intestinal neuroendocrine carcinoma (STC)-1 cell lines. RESULTS: The combination of conditional Men1 deletion in the absence of somatostatin led to the development of gastric carcinoids within 2 years. Suppression of acid secretion by omeprazole accelerated the timeline of carcinoid development to 6 months in the absence of significant parietal cell atrophy. Carcinoids were associated with hypergastrinemia, and correlated with increased Cckbr expression and nuclear export of p27Kip1 both in vivo and in gastrin-treated cell lines. Loss of p27Kip1 was also observed in human gastric carcinoids arising in the setting of atrophic gastritis. CONCLUSIONS: Gastric carcinoids require threshold levels of hypergastrinemia, which modulates p27Kip1 cellular location and stability. PMID- 26860773 TI - Metabolically Active Brown Fat Mimicking Pericardial Metastasis on PET/CT: The Discriminating Role of Cardiac Magnetic Resonance Imaging. AB - Metabolically active mediastinal brown adipose tissue may be mistakenly diagnosed as a malignancy on 18F-fluoro-2-deoxy-D-glucose (FDG)/positron emission tomography (PET). We report the case of a patient with locally recurrent breast carcinoma in which staging PET/CT revealed a suspicious pericardial lesion for which the patient was referred to our centre. The novelty of this case resides in the fact that by tissue characterization, cardiac magnetic resonance imaging allowed the determination that the lesion corresponded to brown fat, a reassuring finding with important impact on management, because the presence of pericardial metastasis would have disqualified this patient for curative resection of her cancer recurrence. PMID- 26860774 TI - Predictive Value of Neutrophil Gelatinase-Associated Lipocalin for Contrast Induced Acute Kidney Injury After Cardiac Catheterization: A Meta-analysis. AB - BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) accumulates in cortical tubules in acute kidney injury (AKI) patients, with its levels associated with serum creatinine. However, the predictive value of NGAL level for contrast-induced acute kidney injury (CI-AKI) remains unclear. METHODS: A total of 1520 patients from 14 relevant studies retrieved from PUBMED, MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, Cochrane Library, and Google Scholar from the inception to November 2014 and 15 data sets were included. RESULTS: The pooled area under the curve of receiver operating characteristic analysis of NGAL for predicting CI-AKI was 0.93, and the diagnostic odds ratio, sensitivity, specificity, and median cutoff value were 42.54, 83.98%, 89.03%, and 52.4 ng/mL, respectively. Urine and serum/plasma NGAL levels performed similarly well in predicting CI-AKI, with somewhat better results obtained when the NGAL level was determined within 4 hours after exposure to contrast medium. CONCLUSIONS: Patient nationality and definition of CI-AKI were important factors that affected the efficiency of NGAL level in predicting CI-AKI. Urine and serum/plasma NGAL levels appear to be promising biomarkers for early detection of CI-AKI after percutaneous coronary intervention or coronary angiography. PMID- 26860775 TI - Interpretation of the Electrocardiogram in Athletes. AB - Regular intensive participation in sport results in electrical and structural alterations within the heart that can manifest on the surface electrocardiogram (ECG). In addition to the actual sporting discipline and the volume and intensity of exercise being performed, other factors play a role in the development of certain ECG patterns including sex, age, and ethnicity. In some instances, large male endurance athletes and those of African or Afro-Caribbean origin (black athletes), might exhibit ECG patterns that overlap with those seen in patients with cardiomyopathy and channelopathies, which are recognized causes of exercise related sudden cardiac death. The ability to distinguish accurately between benign physiological electrical alterations and pathological ECG changes is crucial to prevent the unnecessary termination of an athlete's career and to minimize the risk of sudden death. Several recommendations currently exist to aid the physician in the interpretation of the athlete's ECG. In this review we discuss which ECG patterns can safely be considered benign as opposed to those that should prompt the physician to consider cardiac pathology. PMID- 26860776 TI - Tricuspid Annular Plane Systolic Excursion in Acute Decompensated Heart Failure: Relevance for Risk Stratification. AB - BACKGROUND: Although the prognostic value of right ventricular dysfunction in chronic heart failure (HF) has been studied extensively, it remains insufficiently characterized in the setting of acute decompensated HF (ADHF). We sought to assess whether measurement of tricuspid annular plane systolic excursion (TAPSE) or TAPSE-to-estimated pulmonary arterial systolic pressure (ePASP) ratio allows improvement of risk prediction in ADHF. METHODS: Four hundred ninety-nine patients with ADHF were studied. Cox regression analyses were used to analyze the association of TAPSE and TAPSE-to-ePASP ratio with 1-year mortality and logistic regression analyses to analyze the association of the 2 variables of interest with adverse in-hospital outcome (AiHO) (in-hospital death plus worsening HF). RESULTS: During the 365-day follow-up, 143 patients (28.7%) died. At univariable analysis, both TAPSE (P = 0.026) and TAPSE-to-ePASP ratio (P < 0.0001) were significantly associated with 1-year mortality. At multivariable Cox analysis, age (P = 0.0270), ischemic heart disease (P = 0.020), systolic blood pressure (P = 0.006), log N-terminal pro-B-type natriuretic peptide (NT proBNP) levels (P < 0.0001), serum sodium levels (P = 0.001), and hemoglobin levels (P = 0.001) at admission were independently associated with 1-year mortality. Adjusting for these covariates, neither TAPSE (P = 0.314) nor TAPSE-to ePASP ratio (P = 0.237) remained independently associated with 1-year mortality. Eighty-three patients (16.6%) had an AiHO. At multivariable logistic regression analysis, the TAPSE-to-ePASP ratio was independently associated with an AiHO (P = 0.024). The association of TAPSE alone or ePASP alone was not statistically significant. CONCLUSIONS: Our data strongly suggest that early assessment of TAPSE or TAPSE-to-ePASP ratio does not improve prediction of 1-year mortality over other key risk markers in ADHF. Nonetheless, the TAPSE-to-ePASP ratio did appear to be independently associated with AiHO. PMID- 26860778 TI - Effects of Iron Overload on Cardiac Calcium Regulation: Translational Insights Into Mechanisms and Management of a Global Epidemic. AB - Iron overload cardiomyopathy occurs in a rare primary form (ie, hemochromatosis) and a very common secondary form in a host of hemoglobinopathies (eg, thalassemia, sickle cell anemia) of substantial and growing global prevalence, which have transformed iron overload cardiomyopathy into a worldwide epidemic. Intracellular calcium ([Ca(2+)]i) is known to be a critical regulator of myocardial function, in which it plays a key role in maintaining cardiac excitation-contraction coupling. It has been proposed that a disturbance in cardiac calcium regulation is a major contributor to left ventricular dysfunction in iron overload cardiomyopathy. This review comprehensively summarizes reports concerned with the effects of iron overload on cardiac calcium regulation, including alteration in the intracellular calcium level, voltage-gated calcium channel function, and calcium cycling protein activity. Consistent reports, as well as inconsistent findings, from both in vitro and in vivo studies, are presented and discussed. The understanding of these mechanisms has provided important new pathophysiological insights and has led to the development of novel therapeutic and preventive strategies for patients with iron overload cardiomyopathy that are currently in clinical trials. PMID- 26860777 TI - The Role of Estrogen and Estrogen Receptors on Cardiomyocytes: An Overview. AB - Sex differences in the onset and manifestation of cardiovascular diseases are well known, yet the mechanism behind this discrepancy remains obscure. Estrogen and its corresponding receptors have been studied for their positive salutary effects in women for decades. Estrogen protects the heart from various forms of stress, including cytotoxic, ischemic, and hypertrophic stimuli. The postulated underlying mechanism is complex, and involves the actions of the hormone on the endothelium and myocardium. Although the effects of estrogen on the coronary endothelium are well-described, delineation of the hormone's action on cardiomyocytes is still evolving. The focus of this article is to review the accumulated literature and latest data on the role of estrogen and its receptors on cardiomyocytes, the contractile cellular units of the myocardium. PMID- 26860779 TI - Temporal and Provincial Variation in Ambulance Use Among Patients Who Present to Acute Care Hospitals With ST-Elevation Myocardial Infarction. AB - BACKGROUND: At the first sign or symptoms consistent with an ST-elevation myocardial infarction (STEMI), patients are encouraged to call 9-1-1 and activate emergency medical services immediately. We examined: (1) temporal trends and provincial variations in the proportion of STEMI patients who arrive by ambulance; and (2) the association between patient demographic and clinical characteristics and ambulance use. METHODS: Hospital data for all patients 20 years or older who presented with a primary diagnosis of STEMI between April 1, 2007 and March 31, 2013 in all provinces, except Quebec, were examined to identify ambulance use rates according to year and province. RESULTS: Among 67,232 STEMI hospitalizations (for 66,008 unique patients), the proportion of patients who presented by ambulance increased from 60% in fiscal year (FY) 2007 to 68% in FY 2012. In FY 2012, Alberta had the highest percentage of ambulance use (76%), followed by New Brunswick (73%) and Ontario (72%). At the province level, a higher rate of ambulance use was negatively correlated (r = -0.72; P = 0.04) with in-hospital mortality rate. Patients who presented by ambulance were older and more likely to be female. Self-presenters were more likely to be urban dwellers and present during work hours. Provincial differences in ambulance use remained after adjustment for patient characteristics, overall, and within specific patient subgroups. CONCLUSIONS: The use of ambulance services among patients who presented with STEMI in Canada has increased significantly over the past 5 years, although significant interprovincial variation remains. PMID- 26860780 TI - Ruth E. Brown, Arya M. Sharma, Chris I. Ardern, Pedi Mirdamadi, Paul Mirdamadi and Jennifer L. Kuk. "Secular differences in the association between caloric intake, macronutrient intake, and physical activity with obesity." [Obesity Research & Clinical Practice (2015)]. PMID- 26860781 TI - Improving Polymerase Activity with Unnatural Substrates by Sampling Mutations in Homologous Protein Architectures. AB - The ability to synthesize and propagate genetic information encoded in the framework of xeno-nucleic acid (XNA) polymers would inform a wide range of topics from the origins of life to synthetic biology. While directed evolution has produced examples of engineered polymerases that can accept XNA substrates, these enzymes function with reduced activity relative to their natural counterparts. Here, we describe a biochemical strategy that enables the discovery of engineered polymerases with improved activity for a given unnatural polymerase function. Our approach involves identifying specificity determining residues (SDRs) that control polymerase activity, screening mutations at SDR positions in a model polymerase scaffold, and assaying key gain-of-function mutations in orthologous protein architectures. By transferring beneficial mutations between homologous protein structures, we show that new polymerases can be identified that function with superior activity relative to their starting donor scaffold. This concept, which we call scaffold sampling, was used to generate engineered DNA polymerases that can faithfully synthesize RNA and TNA (threose nucleic acid), respectively, on a DNA template with high primer-extension efficiency and low template sequence bias. We suggest that the ability to combine phenotypes from different donor and recipient scaffolds provides a new paradigm in polymerase engineering where natural structural diversity can be used to refine the catalytic activity of synthetic enzymes. PMID- 26860782 TI - Multi and mixed 3D-printing of graphene-hydroxyapatite hybrid materials for complex tissue engineering. AB - With the emergence of three-dimensional (3D)-printing (3DP) as a vital tool in tissue engineering and medicine, there is an ever growing need to develop new biomaterials that can be 3D-printed and also emulate the compositional, structural, and functional complexities of human tissues and organs. In this work, we probe the 3D-printable biomaterials spectrum by combining two recently established functional 3D-printable particle-laden biomaterial inks: one that contains hydroxyapatite microspheres (hyperelastic bone, HB) and another that contains graphene nanoflakes (3D-graphene, 3DG). We demonstrate that not only can these distinct, osteogenic, and neurogenic inks be co-3D-printed to create complex, multimaterial constructs, but that composite inks of HB and 3DG can also be synthesized. Specifically, the printability, microstructural, mechanical, electrical, and biological properties of a hybrid material comprised of 1:1 HA:graphene by volume is investigated. The resulting HB-3DG hybrid exhibits mixed characteristics of the two distinct systems, while maintaining 3D-printability, electrical conductivity, and flexibility. In vitro assessment of HB-3DG using mesenchymal stem cells demonstrates the hybrid material supports cell viability and proliferation, as well as significantly upregulates both osteogenic and neurogenic gene expression over 14 days. This work ultimately demonstrates a significant step forward towards being able to 3D-print graded, multicompositional, and multifunctional constructs from hybrid inks for complex composite tissue engineering. (c) 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 274-283, 2017. PMID- 26860783 TI - [Effectiveness of an intervention to improve the quality of compliance with the surgical safety checklist in the operations performed by a general surgery department]. PMID- 26860784 TI - [Opioids availability in the intermediate stay palliative care units in Madrid]. PMID- 26860785 TI - Associations between work-related musculoskeletal disorders, quality of life, and workplace stress in physical therapists. AB - This study was performed to determine the associations between work-related musculoskeletal disorders (WMSDs), quality of life (QoL), and workplace stress among physical therapists (PTs) in South Korea. Self-reporting questionnaires were given to 855 PTs. Variables examined included general characteristics, WMSDs, QoL, and workplace stress. Of the 788 PTs who responded, 745 (94.5%) reported WMSDs affecting at least one body site. The most affected WMSDs site was the shoulder (23.3%), and the most reported number of body sites affected by WMSDs was one (50.9%). QoL was significantly improved (p<0.05) among PTs over 39 years old, who had 10-15 years of professional experience, worked in general/university hospitals, and had only one site affected by WMSDs. Factors influencing QoL included number of body sites affected by WMSDs, presence/absence of WMSDs, working venues, workplace stress, and age. Factors affecting workplace stress included number of body sites affected by WMSDs, QoL, work hours, and gender. The results showed a high prevalence of WMSDs among PTs in South Korea, and this negatively affected both QoL and workplace stress. PMID- 26860786 TI - Effect of management training in organizational justice: a randomized controlled trial. AB - Organizational justice (OJ) influences the well-being of employees of organizations. We conducted a randomized controlled trial to examine whether or not brief management training increases OJ for subordinates. Study participants were managers and subordinates working in the private manufacturing sector. Randomization at the departmental level generated an intervention group of 23 departments (93 managers and 248 subordinates) and a control group of 23 departments (91 managers and 314 subordinates). Managers in the intervention group received a 90-min training session to investigate the attitudes and behavior of managers and help increase OJ. Subordinates completed self administered OJ questionnaire surveys on procedural, interpersonal, and informational justice before and 3 months after intervention. For all subordinates, the interaction between group and time in OJ scores obtained before and 3 months after intervention were not significant. However, in subgroup analyses of the lowest tertile group in relation to the baseline of each of the three OJ subscales and total scores, the lowest tertile group of the interpersonal justice subscale showed significant improvement. The results of this study suggest that brief management training in OJ for managers significantly improves a low rating from subordinates in interpersonal justice. Further studies are required to develop a specific intervention method to increase OJ. PMID- 26860787 TI - Certifying leaders? high-quality management practices and healthy organisations: an ISO-9000 based standardisation approach. AB - The present study proposes a set of quality requirements to management practices by taking into account the empirical evidence on their potential effects on health, the systemic nature of social organisations, and the current conceptualisations of management functions within the framework of comprehensive quality management systems. Systematic reviews and meta-analyses focusing on the associations between leadership and/or supervision and health in occupational settings are evaluated, and the core elements of an ISO 9001 standardisation approach are presented. Six major occupational health requirements to high quality management practices are identified pertaining to communication processes, organisational justice, role clarity, decision making, social influence processes and management support. It is concluded that the quality of management practices may be improved by developing a quality management system of management practices that ensures not only conformity to product but also to occupational safety and health requirements. Further research may evaluate the practicability of the proposed approach. PMID- 26860788 TI - Retrogradation enthalpy does not always reflect the retrogradation behavior of gelatinized starch. AB - Starch retrogradation is a term used to define the process in which gelatinized starch undergoes a disorder-to-order transition. A thorough understanding of starch retrogradation behavior plays an important role in maintaining the quality of starchy foods during storage. By means of DSC, we have demonstrated for the first time that at low water contents, the enthalpy change of retrograded starch is higher than that of native starch. In terms of FTIR and Raman spectroscopic results, we showed that the molecular order of reheated retrograded starch samples is lower than that of DSC gelatinized starch. These findings have led us to conclude that enthalpy change of retrograded starch at low water contents involves the melting of recrystallized starch during storage and residual starch crystallites after DSC gelatinization, and that the endothermic transition of retrograded starch gels at low water contents does not fully represent the retrogradation behavior of starch. Very low or high water contents do not favor the occurrence of starch retrogradation. PMID- 26860789 TI - Functionalized graphene as a model system for the two-dimensional metal-insulator transition. AB - Reports of metallic behavior in two-dimensional (2D) systems such as high mobility metal-oxide field effect transistors, insulating oxide interfaces, graphene, and MoS2 have challenged the well-known prediction of Abrahams, et al. that all 2D systems must be insulating. The existence of a metallic state for such a wide range of 2D systems thus reveals a wide gap in our understanding of 2D transport that has become more important as research in 2D systems expands. A key to understanding the 2D metallic state is the metal-insulator transition (MIT). In this report, we explore the nature of a disorder induced MIT in functionalized graphene, a model 2D system. Magneto-transport measurements show that weak-localization overwhelmingly drives the transition, in contradiction to theoretical assumptions that enhanced electron-electron interactions dominate. These results provide the first detailed picture of the nature of the transition from the metallic to insulating states of a 2D system. PMID- 26860791 TI - Role of PAR2 in the Development of Lower Urinary Tract Dysfunction. AB - PURPOSE: Lower urinary tract symptoms are a common finding in patients with chronic prostatitis/chronic pelvic pain syndrome. We previously reported that the mast cell-tryptase-PAR2 (protease activated receptor 2) axis has a critical role in the development of chronic pain in experimental autoimmune prostatitis, a mouse model of chronic prostatitis/chronic pelvic pain syndrome. Therefore, we examined whether PAR2 activation mediates lower urinary tract dysfunction. MATERIALS AND METHODS: Functional cystometry was done in male B6 mice along with immunoblotting and immunohistochemistry for the expression of COL1A1 (collagen type I alpha I) and alpha-SMA (alpha-smooth muscle actin). Flow cytometry analysis was performed on single cell suspensions of the prostate, bladder, lymph nodes and spleen. RESULTS: Experimental autoimmune prostatitis resulted in increased urinary voiding frequency and decreased bladder capacity 30 days after initiation. Concurrently, there was increased expression of COL1A1 and alpha-SMA in the prostates and bladders. In contrast, induction of experimental autoimmune prostatitis in PAR2 knockout mice did not result in altered urodynamics or increased markers of fibrosis in the prostate or the bladder. Single cell suspensions of the prostate, bladder, lymph nodes and spleen demonstrated that in the absence of PAR2 cellular inflammatory mechanisms were still initiated in experimental autoimmune prostatitis but PAR2 expression may be required to maintain chronic inflammation. Finally, antibody mediated PAR2 neutralization normalized urinary voiding frequency and bladder capacity, and attenuated chronic pelvic pain. CONCLUSIONS: PAR2 activation in the prostate may contribute to the development of lower urinary tract dysfunction through proinflammatory as well as profibrotic pathways. PMID- 26860792 TI - Treatment Effects of WST11 Vascular Targeted Photodynamic Therapy for Urothelial Cell Carcinoma in Swine. AB - PURPOSE: Surgical management of upper tract urothelial carcinoma requires kidney and ureter removal, compromising renal function. Nonsurgical alternatives have potentially prohibitive safety concerns. We examined the feasibility and safety of ablation of the ureter and renal pelvis using endoluminal vascular targeted photodynamic therapy in a porcine model. We also report the efficacy of WST11 vascular targeted photodynamic therapy in a murine model. MATERIALS AND METHODS: After receiving approval we performed a total of 28 endoluminal ablations in the ureters and renal pelvis of 18 swine. Intravenous infusion of WST11 (4 mg/kg) followed by 10-minute laser illumination was done via percutaneous access or a retrograde ureteroscopic approach. Animals were followed clinically with laboratory testing, imaging and histology, which were evaluated at several postablation time points. A murine xenograft was created with the 5637 human urothelial cell carcinoma line to determine sensitivity to this therapy. RESULTS: At 24 hours 50 mW/cm laser fluence produced superficial necrosis of the ureter. Deeper necrosis penetrating the muscularis propria or adventitia was produced by treatment with 200 mW/cm in the ureter and the renal pelvis. At 4 weeks superficial urothelium had regenerated over the treatment site. No symptomatic obstruction, clinically relevant hydronephrosis or abnormality of laboratory testing was noted up to 4 weeks. Of the mice 80% had no evidence of tumor 19 days after WST11 vascular targeted photodynamic therapy. CONCLUSIONS: Urothelial cell carcinoma appears to be sensitive to WST11 vascular targeted photodynamic therapy. The depth of WST11 vascular targeted photodynamic therapy treatment effects can be modulated in a dose dependent manner by titrating light intensity. Moreover, when applied to the porcine upper urinary tract, this treatment modality is feasible via antegrade and retrograde access. PMID- 26860793 TI - Comparison of Perioperative and Early Oncologic Outcomes between Open and Robotic Assisted Laparoscopic Prostatectomy in a Contemporary Population Based Cohort. AB - PURPOSE: We compared rates of positive surgical margins, use of postoperative radiation therapy, and perioperative outcomes between robotic assisted laparoscopic and open radical prostatectomy in a contemporary population based cohort. MATERIALS AND METHODS: In the National Cancer Data Base from 2010 through 2011 patients who underwent robotic assisted laparoscopic prostatectomy (73,131) and open radical prostatectomy (23,804) for nonmetastatic prostate adenocarcinoma were identified. Covariates included age, race, Charlson comorbidity index, prostate specific antigen, biopsy Gleason score, clinical stage, final Gleason score, pathological T stage, lymph node dissection, nodal status, facility type, hospital volume and year of surgery. Multivariable logistic regression was used to identify factors associated with positive surgical margins, use of adjuvant/salvage radiation therapy, prolonged length of stay, readmission and 30 day mortality. Outcomes were also compared in 1:1 propensity matched cohorts. RESULTS: Analysis of propensity matched cohorts showed robotic assisted laparoscopic prostatectomy reduced the risk of positive surgical margins (OR 0.88, 95% CI 0.83-0.93, p <0.01), the use of radiation therapy (OR 0.71, 95% CI 0.63-0.80, p <0.01) and 30-day mortality (OR 0.28, 95% CI 0.13-0.60, p <0.01). The protective effect of robotic assisted laparoscopic prostatectomy for positive surgical margins was found in patients with pT2 disease only (pT2-OR 0.85, 95% CI 0.79-0.91, p <0.01; pT3-OR 0.94, 95% CI 0.86-1.04, p=0.2). Similar results were obtained using multivariable regression. CONCLUSIONS: In a contemporary large national cohort, robotic assisted laparoscopic prostatectomy was independently associated with clinically meaningful reductions in positive surgical margins, postoperative radiation therapy and 30-day mortality compared to open radical prostatectomy. The oncologic benefit was primarily in patients with organ confined disease. Limitations were those associated with any observational study, namely the potential for bias due to unmeasured confounders. PMID- 26860794 TI - Seated Tai Chi versus usual activities in older people using wheelchairs: A randomized controlled trial. AB - OBJECTIVE: Compare the effect of seated Tai Chi exercise (intervention) to usual activities on quality of life and depression symptoms in older people using wheelchairs. DESIGN: Randomized controlled trial. SETTING: One long-term care facility in Taiwan. PARTICIPANTS: 86 long-term care residents were screened; 60 were eligible and randomized to Tai Chi group (n=30), or usual activity (n=30). INTERVENTION: One certified trainer provided the intervention group with 40min of seated Tai Chi exercise, three times a week for 26 weeks. Trial registration ACTRN12613000029796. MAIN OUTCOME MEASURES: Quality of Life (WHOQOL (BREF)); depression symptoms (GDS-SF) RESULTS: Participants in the Tai Chi group (M=3.76, SD=3.65) recorded significantly lower GDS-SF scores than participants in the control (M=7.76, SD=5.15) and the Tai Chi group registered significantly higher scores across overall QOL [p=0.03], general health [p=0.04], and the associated domains: physical health [p=0.00], psychological health [p=0.02], social relations [p=0.00], and environment [p=0.00]. CONCLUSIONS: The findings highlight the importance of Tai Chi in improving QOL and depression in this population. PMID- 26860795 TI - Complementary and integrative healthcare for patients with mechanical low back pain in a U.S. hospital setting. AB - OBJECTIVES: Complementary and integrative healthcare (CIH) is commonly used to treat low back pain (LBP). While the use of CIH within hospitals is increasing, little is known regarding the delivery of these services within inpatient settings. We examine the patterns of CIH services among inpatients with mechanical LBP in a hospital setting. METHODS: This is a retrospective, practice based study conducted at Abbot Northwestern hospital in Minnesota. Using electronic health record data from July 2009 to December 2012, 8095 inpatients with mechanical LBP were identified using ICD-9 codes. We classified patients by reason for hospitalization. We examined demographic and clinical characteristics by receipt of CIH services. Then, we estimated the prevalence of types of CIH delivered and clinical foci for CIH visits among inpatients with mechanical LBP. RESULTS: Most inpatients with mechanical LBP (>90%) were hospitalized for surgical procedures. Overall, 14.2% received inpatient CIH services. All demographic and clinical characteristics differed by receipt of CIH (P<0.001), except race/ethnicity. CIH recipients were in poorer health than those who did not. Most commonly delivered CIH services were massage (62.1%), relaxation techniques (42.0%) and acupuncture (25.7%). Pain (45.1%), relaxation (17.5%), and comfort (8.2%) were the top three reasons for CIH visits. CONCLUSION: There are important differences between CIH recipients and non-CIH recipients among patients with mechanical LBP within a hospital setting. The reasons documented for CIH visits included addressing physical, emotional and/or mental conditions of patients. Future studies are needed to determine the effectiveness of CIH services health and wellbeing outcomes in this population. PMID- 26860797 TI - Outcomes of MBSR or MBSR-based interventions in health care providers: A systematic review with a focus on empathy and emotional competencies. AB - BACKGROUND: Emotional competencies are extremely important for healthcare providers exposed to patients' suffering. The effect of mindfulness-based stress reduction (MBSR) has been studied in this population. However, it is unclear whether capacities identified as core for care are modified favourably by this intervention. OBJECTIVES: (1) To identify outcomes in studies on the effect of MBSR in healthcare providers. (2) To evaluate the impact of MBSR on these outcomes. (3) To assess current knowledge on whether capacities central to care are positively impacted by MBSR: empathy, identification of one's own emotions, identification of other's emotions and emotional acceptance. METHODS: We performed a systematic review on interventional studies published up to 2015 evaluating the effect of MBSR in healthcare professionals. A subset of studies including empathy and emotional competencies was assessed for bias following current methodological standards. RESULTS: Thirty nine studies were identified. 14/39 studies measured empathy or some form of emotional competence in healthcare providers. Evidence regarding the effects of MBSR in professionals suggests this intervention is associated with improvements in burnout, stress, anxiety and depression. Improvements in empathy are also suggested but no clear evidence is currently available on emotional competencies. CONCLUSIONS: High quality evidence is available on the effect of MBSR on professionals' mental health. However, while some emotional competencies have been identified as being of major importance for high quality care, they are still scarcely studied. Studying these outcomes is important, as it may help explain how mindfulness contributes to professionals' mental health and thus help develop targeted interventions. PMID- 26860796 TI - A comparison study of metformin only therapy and metformin combined with Chinese medicine jianyutangkang therapy in patients with type 2 diabetes: A randomized placebo-controlled double-blind study. AB - The aim of this 26-week, double-blind, controlled clinical trial, was to compare the efficacy of monotherapy (metformin only) with combination therapy (Chinese medicine prescription JianYuTangKang [JYTK] plus metformin) on type 2 diabetes. All patients on metformin were randomized to receive authenticated JYTK (59 patients) or placebo JYTK (53 patients), 4.5g daily, for 26 weeks. Patients also received information regarding diet and exercise. Fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1C) level, and a lipid profile were measured before, during, and after the treatment. The results of the treatment group (JYTK plus metformin) were noninferior to those of the control group (metformin plus placebo) at 8 and 18 weeks. After 26 weeks of treatment, FPG levels decreased to 6.1+/-1.0mmol/L in the treatment group and 7.0+/-1.5mmol/L in the control group (p<0.01). HbA1C levels after 26 weeks were also significantly decreased in the treatment group compared with the control group (p<0.01). In addition, lipid profiles were also significantly different between the two groups. Integrated traditional Chinese and Western medicine therapy (JYTK plus metformin) for patients with type 2 diabetes mellitus may not only help improve glycemia and insulin sensitivity, but also help to modify the diabetes related lipid equilibrium. And thereby provides a basis for a novel, effective, and safe approach, to treat type 2 diabetic patients. PMID- 26860798 TI - Moral injury: A new challenge for complementary and alternative medicine. AB - Moral injury represents an emerging clinical construct recognized as a source of morbidity in current and former military personnel. Finding effective ways to support those affected by moral injury remains a challenge for both biomedical and complementary and alternative medicine. This paper introduces the concept of moral injury and suggests two complementary and alternative medicine, pastoral care and mindfulness, which may prove useful in supporting military personnel thought to be dealing with moral injury. Research strategies for developing an evidence-base for applying these, and other, complementary and alternative medicine modalities to moral injury are discussed. PMID- 26860799 TI - "We're all in this together": A qualitative study of predominantly low income minority participants in a yoga trial for chronic low back pain. AB - OBJECTIVE: To explore the experiences of low-income minority adults taking part in a yoga dosing trial for chronic low back pain. DESIGN: Individual semi structured interviews were conducted with nineteen participants recruited from a randomized yoga dosing trial for predominantly low-income minority adults with chronic low back pain. Interviews discussed the impact of yoga on low back pain and emotions; other perceived advantages or disadvantages of the intervention; and facilitators and barriers to practicing yoga. Interviews were audio taped and transcribed, coded using ATLAS.ti software, and analyzed with inductive and deductive thematic analysis methods. SETTING: Boston Medical Center, Boston, MA, USA. RESULTS: Participants viewed yoga as a means of pain relief and attributed improved mood, greater ability to manage stress, and enhanced relaxation to yoga. Overall, participants felt empowered to self-manage their pain. Some found yoga to be helpful in being mindful of their emotions and accepting of their pain. Trust in the yoga instructors was a commonly cited facilitator for yoga class attendance. Lack of time, motivation, and fear of injury were reported barriers to yoga practice. CONCLUSIONS: Yoga is a multidimensional treatment for low back pain that has the potential to favorably impact health in a predominantly low income minority population. PMID- 26860800 TI - Effects of ginseng on peripheral blood mitochondrial DNA copy number and hormones in men with metabolic syndrome: A randomized clinical and pilot study. AB - BACKGROUND: It has been observed that mitochondrial dysfunction is associated with an increased risk of metabolic syndrome. There is growing evidence that hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis and hormone (testosterone and growth hormone) deficiency may lead to metabolic syndrome. Recent studies have reported that ginseng treatment improves mitochondrial and HPA-axis function and increases anabolic hormone secretion. OBJECTIVES: The objective of this study was to investigate the effect of red ginseng (RG) on metabolic syndrome, hormones, and mitochondrial function using leukocyte mitochondrial DNA copy number in men with metabolic syndrome. METHODS: We performed a randomized, double-blind, placebo-controlled study in 62 subjects who were not taking drugs that could affect their metabolic function. A total of 62 men with metabolic syndrome were randomly assigned to either an RG group (3.0g/day) or a placebo group for 4 weeks. We analyzed changes in metabolic syndrome components, leukocyte mitochondrial DNA copy number, hormones (total testosterone, IGF-1, cortisol, and DHEAS) and inflammatory markers (C-reactive protein, ferritin) from baseline to 4 weeks. RESULTS: Significant improvement in mitochondrial function (95% CI -44.9 to -1.3) and an increase in total testosterone (95% CI -70.1 to -1.0) and IGF-1(P=0.01) levels were observed in the RG group when compared with the placebo group. Diastolic blood pressure (95% CI 2.0-9.4) and serum cortisol (95% CI 1.1-5.5) significantly decreased in the RG group. CONCLUSIONS: We found evidence that RG had a favorable effect on mitochondrial function and hormones in men with metabolic syndrome. PMID- 26860801 TI - Anti-cancer effects of traditional Korean wild vegetables in complementary and alternative medicine. AB - This research study explored the anti-cancer effects of natural materials in South Korea. Although South Korea has a long history of traditional medicine, many natural materials of South Korea have not yet been introduced to the rest of the world because of language barriers and inconsistent study conditions. In the past 3 years, 56 papers introducing 56 natural materials, which have anti-cancer effects, have been published by scientists in South Korea. Further, these studies have introduced five kinds of natural materials presented in research papers that were written in Korean and are therefore virtually unknown overseas. The anti cancer effects were confirmed by 2-3 cancer markers in the majority of the studies, with the most common targets being breast cancer cells and gastric cancer cells. These cancers have the greatest incidence in South Korea. The natural materials studied not only exhibit anti-cancer activity but also display anti-inflammatory, anti-oxidative stress, and anti-diabetic activities. They have not yet been used for the direct treatment of disease but have potential as medicinal materials for alternative and complementary medicine for the treatment of many modern diseases. Many natural materials of South Korea are already known all over the world, and with this study, we hope to further future research to learn more about these natural medicines. PMID- 26860802 TI - Traditional Chinese Medicine treatment as maintenance therapy in advanced non small-cell lung cancer: A randomized controlled trial. AB - OBJECTIVES: Maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) is an increasingly hot topic in the field of clinical NSCLC research. This study aimed to evaluate the effects of Traditional Chinese Medicine (TCM) treatment as maintenance therapy on time to progression (TTP), quality of life (QOL), overall survival (OS) and 1-year survival rate in patients with advanced NSCLC. METHODS: This study was conducted as a randomized, controlled, open-label trial. 64 non-progressive patients who responded to initial therapy were randomized 1:1 to the TCM arm (treated with herbal injection (Cinobufacini, 20ml/d, d1-d10), herbal decoction (d1-d21) and Chinese acupoint application (d1-d21), n=32) or to the chemotherapy arm (treated with pemetrexed (non-squamous NSCLC, 500mg/m(2), d1), docetaxel (75mg/m(2), d1) or gemcitabine (1250mg/m(2), d1 and d8), n=32). Each therapy cycle was 21 days. They were repeated until disease progression, unacceptable toxicity, or until the patients requested therapy discontinuation. The primary end point was TTP; the secondary end points were QOL, OS and 1-year survival rate. "Intention-to-treat" analysis included all randomized participants. RESULTS: TCM treatment prolonged median TTP for 0.7 months compared with chemotherapy, but it was not statistically significant (3.0 months vs. 2.3 months, P=0.114). Median OS time for TCM treatment did not offer a significant advantage over for chemotherapy (21.5 months vs. 18.8 months, P=0.601). 1-year survival rate of TCM treatment significantly improved than that of chemotherapy (78.1% vs. 53.1%, P=0.035). TCM treatment can significantly improve QOL when compared to chemotherapy as assessed by EORTC QLQ-C30 and EORTC QLQ-LC13 QOL instruments. CONCLUSIONS: TCM maintenance treatment had similar effects on TTP and OS compared with maintenance chemotherapy, but it improved patients' QOL and had higher 1-year survival rate. TCM Maintenance treatment is a promising option for advanced NSCLC patients without progression following first-line chemotherapy. PMID- 26860803 TI - The pathological effects of sleep deprivation on coronary heart disease and treatment using Chinese medicine tranquilization. AB - Sleep deprivation is associated with the morbidity and mortality of coronary heart disease due to pathological factors including sympathetic activation, high blood pressure, arrhythmia, neuroendocrine dysfunction, oxidative stress, endothelial malfunction, inflammatory reaction, and glycolipid metabolism disorders. This article summarizes findings of traditional Chinese medicine tranquilization methods in different studies that indirectly treat coronary heart disease by removing the pathological factors of sleep deprivation. It has been suggested that the traditional Chinese medicine tranquilization methods improve the pathological factors of sleep deprivation with a multiple-component, multiple target and multiple-pathway approach that may be a treatment for coronary heart disease, which also reflects the purpose of psycho-cardiology treatment. PMID- 26860804 TI - Effect of placebo acupuncture over no-treatment: A simple model incorporating the placebo and nocebo effects. AB - Conventionally in controlled trials of drugs or modalities, the placebo and nocebo effects have been determined separately and understood to be the difference between the placebo and no-treatment groups. Recently, the effect of placebo acupuncture over no-treatment was found to be associated with the placebo and nocebo effects together. If these two effects are inseparable in acupuncture treatment, the conventional method of determining placebo and nocebo effects at the trial level will not reflect pure placebo or nocebo effects. Furthermore, if these effects are inseparable, observations about the efficacy of acupuncture will be biased when considering only the placebo effect. A simple mathematical model incorporating both the placebo and nocebo effects will be provided to see how the efficacy of acupuncture is affected. PMID- 26860805 TI - Is complementary and alternative medicine use associated with cancer screening rates for women with functional disabilities? AB - OBJECTIVES: The purpose of this study was to examine the associations of complementary and alternative medicine (CAM) use with mammogram and Pap test rates and functional disabilities (FDs). DESIGN: Cross-sectional study. SETTING: Data were derived from the 2012 National Health Interview Survey (n=6576). ANALYSIS: FDs was defined as physical and/or social limitations. The weighted logistic regression models were performed using SAS software. Study covariates were age, race, education, marital status, usual source of care, and insurance. RESULTS: Of 6576 women, a majority were Caucasian (87%), with GED or less (40%), married (50%), having usual source of care (96%) and health insurance (91%), and with FDs (56%). The results indicated that some CAM practices were negatively associated with increased mammogram and Pap test rates while other CAM practices were positively associated. The results indicated that CAM practices that contribute to musculoskeletal problems such as acupuncture and massage were associated with the increased mammogram and Pap test rates. Contrary, women who used chiropractic manipulation, biofeedback, guided imagery, and energy hearing therapy were less likely to obtain cancer screenings regularly regardless of having FDs. CONCLUSIONS: The use of several CAM therapies was more likely to be associated with mammogram and Pap test frequency, indicating that the CAM use may be associated with better screening rates due to the improvement of musculoskeletal problems. It is important to determine how each CAM therapy improves secondary health conditions in clinical trials to increase cancer screening rates for women with FDs. PMID- 26860806 TI - Prolonged lifetime by adjunct homeopathy in cancer patients-A case of immortal time bias. PMID- 26860807 TI - Chinese herbal medicine as maintenance therapy for improving the quality of life for advanced non-small cell lung cancer patients. AB - OBJECTIVE: The purpose of the study was to assess the efficacy and safety of using Chinese herbal medicine (CHM) as maintenance therapy considering the survival of advanced non-small-cell lung cancer (NSCLC) patients after first-line conventional platinum-based chemotherapy. DESIGN: An open-label, randomized, controlled trial. SETTING: Four hospitals in China. INTERVENTIONS AND MAIN OUTCOME MEASURES: A total of 106 patients were eligible and randomly divided into two groups from four hospitals in China. Both groups received the best supporting care (BSC). Additionally, patients in the trial group were given CHM every day until the disease became aggravated or the patients resigned. The study took both progression-free survival (PFS) and quality of life (QOL) as the primary outcomes to comprehensively evaluate the effect of the treatment. QOL was measured by the Functional Assessment of Cancer Therapy-Lung (FACT-L) 4.0 questionnaire. Side effects and safety were evaluated at the same time. RESULTS: Of the 106 patients, 99 completed the study. After treatment and follow-up for PFS, there were no significant differences in the median PFS time and the 6-month PFS probability between the two groups. However, the 3-month PFS probability in the trial group was significantly higher than that in the control group (FAS, PPS: P<0.01). For QOL, there were significant differences between the two groups in the following: physical well-being, emotional well-being, functional well-being, lung cancer symptom domain and total score of the FACT-L4.0 (FAS, PPS: P<0.05). There was no significant difference in the social well-being domain. No serious adverse side effects to the treatment were observed. CONCLUSIONS: CHM is well tolerated and may improve the QOL of advanced NSCLC patients. CHM is worth studying in future investigations. PMID- 26860809 TI - Impact of prebiotic supplementation on T-cell subsets and their related cytokines, anthropometric features and blood pressure in patients with type 2 diabetes mellitus: A randomized placebo-controlled Trial. AB - BACKGROUNDS AND AIMS: Type 2 diabetic mellitus (T2DM) asone of the main causes of morbidity and mortality is associated with immune system disturbances and metabolic abnormalities. In the current study we aimed to evaluate the effects of oligofructose-enriched inulin on T-cell subsets and their related cytokines, anthropometric and metabolic parameters in patients with T2DM. METHODS: Forty-six diabetic females patients were randomly allocated into intervention (n=27) and control (n=22) groups. Subjects in the intervention group received a daily dose of 10g of oligofructose-enriched inulin and subjects in control group received a placebo for two months. Anthropometric variables, metabolic parameters including fasting serum glucose (FSG), hemoglobin A1c (HbA1c), lipid profile and blood pressure were measured at the beginning and after two months. Immune markers also included serum interleukin (IL)-4, IL-12 and interferon (IFN)-gamma concentrations were assessed and CD3(+), CD4(+), CD8(+) and CD11b(+)T-cell counts were determined by flow cytometry at baseline and end of the trial. RESULTS: After two months intervention, significant improvements in anthropometric variables, blood pressure and serum lipids occurred in prebiotic-treated group (P<0.001). Serum IL-4, IL-12 and IFN-gamma concentrationsalso significantly decreased in intervention group (P<0.001). No significant changes in CD3(+), CD4(+), CD8(+) and CD11b(+) T-cell counts were observed in treatment groups after intervention. CONCLUSION: The present study showed several beneficial effects of oligofructose-enriched inulin on the improvement of the glycemic status, lipid profile, and immune markers in patients with T2DM. Further studies are needed to confirming our findings and to better clarify the underlying mechanisms. PMID- 26860808 TI - Effects of Vitex agnus and Flaxseed on cyclic mastalgia: A randomized controlled trial. AB - OBJECTIVES: Evidence on the effect of Vitex agnus and Flaxseed on cyclical mastalgia is not enough. This study aimed to assess the efficacy of V. agnus and Flaxseed on cyclical mastalgia. DESIGN AND SETTING: This randomized controlled trial was conducted on 159 women referred to health centers of Tabriz, Iran. Subjects were allocated into three groups (n=53 per group) using block randomization. INTERVENTIONS AND MAIN OUTCOME MEASURES: Group I received 25g daily Flaxseed powder and placebo of V. agnus; group II received daily 3.2-4.8mg V. agnus tablet and placebo of Flaxseed and control group received both placebo. Nominal day breast pain was applied at baseline, first, and second month after the intervention. Data was analyzed using general linear model. RESULTS: There was no statistical significant difference between the three groups in terms of socio-demographic characteristics and baseline values. The breast pain improved significantly in both intervention groups during the first and second month after intervention. Mean NDBP score was significantly lower than that in the control group at the first month after the intervention in the Flaxseed [adjusted mean difference: -3.1 (95% CI: -4.2 to -2.0)] and V. agnus groups [-3.3 (-4.3 to 2.2)] and the second month after the intervention in Flaxseed [-7.0 (-8.1 to 5.9)] and V. agnus groups [-6.4 (-7.5 to -5.3)]. CONCLUSION: Flaxseed and V. agnus are effective in short-term period in decreasing cyclical mastalgia. However, further studies are needed to examine the long-term effectiveness and sustainability of the effects after stopping the treatment in order to decide whether these alternative treatments are suitable to treat mastalgia or not. PMID- 26860810 TI - Direct electrical stimulation on the injured ulnar nerve using acupuncture needles combined with rehabilitation accelerates nerve regeneration and functional recovery-A case report. AB - OBJECTIVE: This study illustrates that direct electrical stimulation (ES) improve functional recovery and time of return to work evaluated by prognostic scoring system after ulnar nerve injury. DESIGN: The Rosen and Lundborg (R&L) protocol, Disabilities of the Arm, Shoulder and Hand (DASH) scores, and electromyography were applied for measuring improvements after direct ES intervention. SETTING: A 32-year-old male with deep cutting wound and total rupture of right proximal forearm ulnar nerve was treated using direct ES and daily rehabilitation activities. INTERVENTION: Direct ES, transmitted using 2 acupuncture needles inserted in the cubital tunnel, was applied along the site of the injured ulnar nerve. Other needles were placed according to muscle origins and insertions. All needles were connected to electrical stimulators. We executed these procedures once per week and conducted rehabilitating activities daily. MAIN OUTCOME MEASURES: The R&L protocol, DASH scores, and electromyography were used to measure the intervention outcomes. RESULTS: The total score in the R&L protocol was 0.703 of the initial state; the sensory domain contributed the least amount. Among the improved numerical factors, pain/discomfort domain was the first to reach a stable ameliorative state in the first month. The sensory and motor domains reached stable growth in fourth and third months, respectively. The patient returned to the previous job in third month; his time off work was 75 days. CONCLUSIONS: Directly applying ES to the proximal site of an injured nerve can augment nerve regeneration through three suspected mechanisms. Although direct ES on the injured nerve contributed to an effective recovery of this patient with minimal adverse effects, additional investigation of treatment protocols is warranted and the actual mechanism must be identified. PMID- 26860811 TI - Cervical spinal epidural abscess following acupuncture and wet-cupping therapy: A case report. AB - OBJECTIVE: Report of an uncommon complication of acupuncture and wet cupping. METHODS: A 54-year-old man presented with neck pain and fever. Magnetic resonance imaging of the cervical spine revealed an epidural abscess at C4 to T2. RESULTS: The symptoms related to epidural abscess resolved partially after treatment with antibiotics. CONCLUSION: Acupuncture and wet-cupping therapy should be taken into consideration as a cause of spinal epidural abscesses in patients who present with neck pain and fever. Furthermore, acupuncture and wet-cupping practitioners should pay attention to hygienic measures. PMID- 26860812 TI - Comparison of homeopathic globules prepared from high and ultra-high dilutions of various starting materials by ultraviolet light spectroscopy. AB - OBJECTIVE: Homeopathic globules are commonly used in clinical practice, while research focuses on liquid potencies. Sequential dilution and succussion in their production process has been proposed to change the physico-chemical properties of the solvent(s). It has been reported that aqueous potencies of various starting materials showed significant differences in ultraviolet light transmission compared to controls and between different dilution levels. The aim of the present study was to repeat and expand these experiments to homeopathic globules. METHODS: Globules were specially produced for this study by Spagyros AG (Gumligen, Switzerland) from 6 starting materials (Aconitum napellus, Atropa belladonna, phosphorus, sulfur, Apis mellifica, quartz) and for 6 dilution levels (6x, 12x, 30c, 200c, 200CF (centesimal discontinuous fluxion), 10,000CF). Native globules and globules impregnated with solvents were used as controls. Globules were dissolved in ultrapure water, and absorbance in the ultraviolet range was measured. The average absorbance from 200 to 340nm was calculated and corrected for differences between measurement days and instrumental drift. RESULTS: Statistically significant differences were found for A. napellus, sulfur, and A. mellifica when normalized average absorbance of the various dilution levels from the same starting material (including control and solvent control globules) was compared. Additionally, absorbance within dilution levels was compared among the various starting materials. Statistically significant differences were found among 30c, 200c and 200CF dilutions. CONCLUSION: This study has expanded previous findings from aqueous potencies to globules and may indicate that characteristics of aqueous high dilutions may be preserved and detectable in dissolved globules. PMID- 26860813 TI - Effects of traditional Korean medicine on anti-Mullerian hormone in patients with diminished ovarian reserve: A retrospective study. AB - OBJECTIVE: The purpose of the present study is to retrospectively evaluate the effect of traditional Korean medicine (TKM) on ovarian reserve by measuring serum anti-Mullerian hormone (AMH) levels in patients with diminished ovarian reserve (DOR). STUDY DESIGN: We performed a retrospective chart review of patients with DOR who had received TKM for at least 2 months and had undergone serum AMH tests before and after TKM treatment. A total of 22 patients with DOR were included in the study. RESULTS: There were no significant differences in AMH levels before and after TKM in all patients (n=22, p=0.237). However, when the study population was divided into two age groups (<38 (n=12) and >=38 years (n=10)) to determine whether there was a age-related difference in the effect of TKM with DOR, a significant increase in AMH levels before and after TKM was observed in the age <38 (p<0.05). CONCLUSIONS: TKM may provide an effective option for patients aged <38 years with DOR, but it should be interpreted cautiously as more rigorous research is needed. Further studies in a larger population are needed to confirm these results and to evaluate the effects of improved ovarian reserve on fertility outcomes following TKM in patients with DOR. PMID- 26860814 TI - Complementary therapies and integrative medicine. PMID- 26860815 TI - Soil properties drive a negative correlation between species diversity and genetic diversity in a tropical seasonal rainforest. AB - A negative species-genetic diversity correlation (SGDC) could be predicted by the niche variation hypothesis, whereby an increase in species diversity within community reduces the genetic diversity of the co-occurring species because of the reduction in average niche breadth; alternatively, competition could reduce effective population size and therefore genetic diversity of the species within community. We tested these predictions within a 20 ha tropical forest dynamics plot (FDP) in the Xishuangbanna tropical seasonal rainforest. We established 15 plots within the FDP and investigated the soil properties, tree diversity, and genetic diversity of a common tree species Beilschmiedia roxburghiana within each plot. We observed a significant negative correlation between tree diversity and the genetic diversity of B. roxburghiana within the communities. Using structural equation modeling, we further determined that the inter-plot environmental characteristics (soil pH and phosphorus availability) directly affected tree diversity and that the tree diversity within the community determined the genetic diversity of B. roxburghiana. Increased soil pH and phosphorus availability might promote the coexistence of more tree species within community and reduce genetic diversity of B. roxburghiana for the reduced average niche breadth; alternatively, competition could reduce effective population size and therefore genetic diversity of B. roxburghiana within community. PMID- 26860816 TI - Yttrium Iron Garnet Thin Films with Very Low Damping Obtained by Recrystallization of Amorphous Material. AB - We have investigated recrystallization of amorphous Yttrium Iron Garnet (YIG) by annealing in oxygen atmosphere. Our findings show that well below the melting temperature the material transforms into a fully epitaxial layer with exceptional quality, both structural and magnetic. In ferromagnetic resonance (FMR) ultra low damping and extremely narrow linewidth can be observed. For a 56 nm thick layer a damping constant of alpha = (6.15 +/- 1.50) . 10(-5) is found and the linewidth at 9.6 GHz is as small as 1.30 +/- 0.05 Oe which are the lowest values for PLD grown thin films reported so far. Even for a 20 nm thick layer a damping constant of alpha = (7.35 +/- 1.40) . 10(-5) is found which is the lowest value for ultrathin films published so far. The FMR linewidth in this case is 3.49 +/- 0.10 Oe at 9.6 GHz. Our results not only present a method of depositing thin film YIG of unprecedented quality but also open up new options for the fabrication of thin film complex oxides or even other crystalline materials. PMID- 26860817 TI - Disparity between vitamin A-induced Th1-dependent oral tolerance in newborn mice and vitamin A-induced atopic sensitization in Guinean girls. PMID- 26860820 TI - Climate and Fuel Controls on North American Paleofires: Smoldering to Flaming in the Late-glacial-Holocene Transition. AB - Smoldering and flaming fires, which emit different proportions of organic (OC) and black carbon (BC, in the form of char and soot), have long been recognized in modern wildfire observations but never in a paleo-record, and little is known about their interactions with climate. Here we show that in the late glacial early Holocene transition period, when the climate was moist, relatively high quantities of char were deposited in Linsley Pond, Connecticut, USA while soot was more abundant during the warmer and drier early Holocene interval. The highest soot mass accumulation rates (MARs) occurred at the beginning of the Holocene as fuel availability increased through the climatic transition when boreal forests were locally extirpated. These variations with time are related to the different formation pathways of char and soot, which are governed by combustion efficiency. This study provides an approach for differentiating smoldering from flaming combustion in paleo-wildfire reconstructions. Our results suggest that climate and fuel loads control the occurrence of different wildfire types and precipitation may play a key role. PMID- 26860819 TI - Response to "Disparity between vitamin A-induced Th1-dependent oral tolerance in newborn mice and vitamin A-induced atopic sensitization in Guinean girls". PMID- 26860818 TI - Mast cell-derived neurotrophin 4 mediates allergen-induced airway hyperinnervation in early life. AB - Asthma often progresses from early episodes of insults. How early-life events connect to long-term airway dysfunction remains poorly understood. We demonstrated previously that increased neurotrophin 4 (NT4) levels following early-life allergen exposure cause persistent changes in airway smooth muscle (ASM) innervation and airway hyper-reactivity (AHR) in mice. Herein, we identify pulmonary mast cells as a key source of aberrant NT4 expression following early insults. NT4 is selectively expressed by ASM and mast cells in mice, nonhuman primates, and humans. We show in mice that mast cell-derived NT4 is dispensable for ASM innervation during development. However, upon insults, mast cells expand in number and degranulate to release NT4 and thus become the major source of NT4 under pathological condition. Adoptive transfer of wild-type mast cells, but not NT4-/- mast cells restores ASM hyperinnervation and AHR in KitW-sh/W-sh mice following early-life insults. Notably, an infant nonhuman primate model of asthma also exhibits ASM hyperinnervation associated with the expansion and degranulation of mast cells. Together, these findings identify an essential role of mast cells in mediating ASM hyperinnervation following early-life insults by producing NT4. This role may be evolutionarily conserved in linking early insults to long-term airway dysfunction. PMID- 26860822 TI - Need for a forum where young doctors can express feelings about patients. PMID- 26860821 TI - A non-invasive magnetic resonance imaging-based model predicts portal venous pressure. AB - OBJECTIVE: To establish a non-invasive model for the assessment of portal venous pressure (PVP) based on the magnetic resonance (MR) parameters. METHODS: In this prospective study, contrast-enhanced magnetic resonance imaging (MRI) scan was performed in 109 patients indicated for upper abdominal surgeries after their written consents were obtained, and intraoperative PVP measurements were completed in 92 patients. Altogether 17 patients were excluded for not undergoing surgery or unsuccessful catheterization. A linear model was constructed for estimating PVP levels in 56 patients and further validation was conducted in the other 36 patients. RESULTS: The PVP levels were significantly correlated with MR parameters, including splenic volume (SV), splenic venous diameter (SVD), liver/splenic volume ratio, portal venous diameter, hepatic diameter, portal venous cross-sectional area, ascites, varices and arterial portal shunts. A linear model was established as follows: PVP (mmHg) = 2.529 + 1.572 * SVD (mm) + 0.231 * SV/body mass index (* 10(4) cm(5) /kg) + 3.44 * aspartate aminotransferase-to-platelet ratio index. This model showed excellent accuracy in the detection of portal hypertension, with the area under the receiver operating characteristic curve (AUROC) of 0.945 (95% CI 0.867-1.000), with the sensitivity and specificity of 91.7% and 93.7%, respectively. The agreement analysis revealed that the predictive value using this formula closely reflected the patients' actual PVP level. Moreover, the validation confirmed the accuracy of this model for the assessment of portal hypertension [AUROC 0.935 (95% CI 0.856-1.000)]. CONCLUSIONS: The MRI-based formula has great potential for detecting portal hypertension. As a non-invasive measurement, it may be clinically accepted for the replacement of invasive modalities after further refinement. PMID- 26860823 TI - Development of a Tablet-based symbol digit modalities test for reliably assessing information processing speed in patients with stroke. AB - PURPOSE: To develop a Tablet-based Symbol Digit Modalities Test (T-SDMT) and to examine the test-retest reliability and concurrent validity of the T-SDMT in patients with stroke. METHODS: The study had two phases. In the first phase, six experts, nine college students and five outpatients participated in the development and testing of the T-SDMT. In the second phase, 52 outpatients were evaluated twice (2 weeks apart) with the T-SDMT and SDMT to examine the test retest reliability and concurrent validity of the T-SDMT. RESULTS: The T-SDMT was developed via expert input and college student/patient feedback. Regarding test retest reliability, the practise effects of the T-SDMT and SDMT were both trivial (d=0.12) but significant (p?0.015). The improvement in the T-SDMT (4.7%) was smaller than that in the SDMT (5.6%). The minimal detectable changes (MDC%) of the T-SDMT and SDMT were 6.7 (22.8%) and 10.3 (32.8%), respectively. The T-SDMT and SDMT were highly correlated with each other at the two time points (Pearson's r=0.90-0.91). CONCLUSIONS: The T-SDMT demonstrated good concurrent validity with the SDMT. Because the T-SDMT had a smaller practise effect and less random measurement error (superior test-retest reliability), it is recommended over the SDMT for assessing information processing speed in patients with stroke. Implications for Rehabilitation The Symbol Digit Modalities Test (SDMT), a common measure of information processing speed, showed a substantial practise effect and considerable random measurement error in patients with stroke. The Tablet-based SDMT (T-SDMT) has been developed to reduce the practise effect and random measurement error of the SDMT in patients with stroke. The T-SDMT had smaller practise effect and random measurement error than the SDMT, which can provide more reliable assessments of information processing speed. PMID- 26860824 TI - Therapists' Perceptions of Their Encounter With Sex Offenders. AB - Despite the increasing interest in therapists' responses to their encounter with sex offenders, there is a lack of research on their subjective perceptions of this encounter and on their experience working with this client population. The study presented in this article is part of a larger qualitative research project conducted among 19 social workers (12 were women and 7 were men; their ages ranged from 30 to 66 years; 15 of them were Jewish and 4 were Arab). In-depth semi-structured interviews were conducted to examine their attitudes toward and perceptions of their encounter with sex offenders. The questions related to the therapists' perceptions regarding motives for committing sex offenses, therapists' perceptions of sex offenders, therapists' perceptions of the victims of sex offenders, and therapists' perceptions of the nature of their professional role. In this article, emphasis is placed on the development and changes of the therapists' perceptions following that encounter. The following five major domains of perceptions were revealed in the study: Therapists' perceptions of the offenders' personal motives for committing sex offenses, therapists' perceptions of sex offenders, therapists' perceptions of the experience of victimization, the process of changing perceptions, and the nature of the therapists' role. The results are discussed in light of Ajzen's conceptualization of the process of acquiring beliefs. The limitations of the study as well as its implications for future research and for shaping the perceptions of therapists toward sex offenders are discussed. PMID- 26860825 TI - A practical method for predicting frequent use of emergency department care using routinely available electronic registration data. AB - BACKGROUND: Accurately predicting future frequent emergency department (ED) utilization can support a case management approach and ultimately reduce health care costs. This study assesses the feasibility of using routinely collected registration data to predict future frequent ED visits. METHOD: Using routinely collected registration data in the state of Indiana, U.S.A., from 2008, we developed multivariable logistic regression models to predict frequent ED visits in the subsequent two years. We assessed the model's accuracy using Receiver Operating Characteristic (ROC) curves, sensitivity, and positive predictive value (PPV). RESULTS: Strong predictors of frequent ED visits included age between 25 and 44 years, female gender, close proximity to the ED (less than 5 miles traveling distance), total visits in the baseline year, and respiratory and dental chief complaint syndromes. The area under ROC curve (AUC) ranged from 0.83 to 0.92 for models predicting patients with 8 or more visits to 16 or more visits in the subsequent two years, suggesting acceptable discrimination. With 25 % sensitivity, the model predicting frequent ED use as defined as 16 or more visits in 2009 and 2010 had a PPV of 59.5 % and specificity of 99.9 %. The "adjusted" PPV of this model, which includes patients having 8 or more visits, is 81.9 %. CONCLUSION: We demonstrate a strong association between predictor variables present in registration data and frequent ED use. The algorithm's performance characteristics suggest that it is technically feasible to use routinely collected registration data to predict future frequent ED use. PMID- 26860826 TI - Transforming a team of experts into an expert team. PMID- 26860828 TI - Intraductal papilloma of the male breast. AB - We report the case of a 29-year-old male patient who presented with a painless lump of his left breast that was found to be an intraductal papilloma. This is an extremely rare, but benign disease in the male breast. We subsequently discuss radiologic tests and treatment options. PMID- 26860827 TI - An immunohistochemical study of cyclin-dependent kinase 5 (CDK5) expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC): a possible prognostic biomarker. AB - BACKGROUND: Cyclin-dependent kinase 5 (CDK5) is an atypical CDK which plays a vital role in several cancers via regulating migration and motility of cancer cells. However, the clinicopathological impact and function of CDK5 in lung cancer remain poorly understood. The present study was aimed at exploring expression and clinicopathological significance of CDK5 in lung cancer. METHODS: There were 395 samples of lung tissue including 365 lung tumors (339 non-small cell lung cancers and 26 small cell lung cancers) and 30 samples of normal lung. CDK5 expression was detected by immunohistochemistry on lung tissue microarrays. RESULTS: Over expression was detected in lung cancer compared with normal lung tissues (P=0.001). Furthermore, area under curve (AUC) of receiver operating characteristic (ROC) of CDK5 was 0.685 (95% CI 0.564~0.751, P=0.004). In lung cancer, we also discovered close correlations between CDK5 and pathological grading (r=0.310, P<0.001), TNM stage (r=0.155, P=0.003), and lymph node metastasis (r=0.279, P<0.001) by using Spearman analysis. In two subgroups of non small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), the expression of CDK5 was also higher than that of normal lung tissue, respectively (P=0.001 and P=0.004). Moreover, in NSCLCs, Spearman analysis revealed that expression of CDK5 was correlated with TNM stages (r=0.129, P=0.017), lymph node metastasis (r=0.365, P<0.001), and pathological grading (r=0.307, P<0.001), respectively. The significant correlation was also found between CDK5 expression and TNM stages (r=0.415, P=0.049) and lymphatic metastasis (r=0.469, P=0.024) in SCLCs. CONCLUSIONS: The results of this present study suggest that the CDK5 expression is associated with several clinicopathological factors linked with poorer prognosis. PMID- 26860829 TI - Hamostaseologie--Progress in Haemostasis. GTH is moving to a European scientific society. PMID- 26860830 TI - Platelet pathology and antiplatelet strategies. Resolved and unresolved issues. PMID- 26860831 TI - Idiopathic pulmonary fibrosis - clinical management guided by the evidence-based GRADE approach: what arguments can be made against transparency in guideline development? AB - Evidence-based guidelines have undergone an incredible transformation over the last number of years. Significant advances include explicit linkages of systematic evidence summaries to the strength and direction of recommendations, consideration of all patient-important factors, transparent reporting of the recommendation generation process including conflict of interest management strategies and the production of clinical practice guidelines which use simple and clear language. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology provides a framework for guideline development and was employed to produce the recently published ATS/ERS/JRS/ALAT update on treatment for idiopathic pulmonary fibrosis (IPF). Herein we discuss the advantages of using an evidence-based approach for guideline development using the IPF process and resultant document as an example. PMID- 26860833 TI - Diet-induced and mono-genetic obesity alter volatile organic compound signature in mice. AB - The prevalence of obesity is still rising in many countries, resulting in an increased risk of associated metabolic diseases. In this study we aimed to describe the volatile organic compound (VOC) patterns symptomatic for obesity. We analyzed high fat diet (HFD) induced obese and mono-genetic obese mice (global knock-in mutation in melanocortin-4 receptor MC4R-ki). The source strengths of 208 VOCs were analyzed in ad libitum fed mice and after overnight food restriction. Volatiles relevant for a random forest-based separation of obese mice were detected (26 in MC4R-ki, 22 in HFD mice). Eight volatiles were found to be important in both obesity models. Interestingly, by creating a partial correlation network of the volatile metabolites, the chemical and metabolic origins of several volatiles were identified. HFD-induced obese mice showed an elevation in the ketone body acetone and acrolein, a marker of lipid peroxidation, and several unidentified volatiles. In MC4R-ki mice, several yet unidentified VOCs were found to be altered. Remarkably, the pheromone (methylthio)methanethiol was found to be reduced, linking metabolic dysfunction and reproduction. The signature of volatile metabolites can be instrumental in identifying and monitoring metabolic disease states, as shown in the screening of the two obese mouse models in this study. Our findings show the potential of breath gas analysis to non-invasively assess metabolic alterations for personalized diagnosis. PMID- 26860834 TI - Decoding power-spectral profiles from FMRI brain activities during naturalistic auditory experience. AB - Recent studies have demonstrated a close relationship between computational acoustic features and neural brain activities, and have largely advanced our understanding of auditory information processing in the human brain. Along this line, we proposed a multidisciplinary study to examine whether power spectral density (PSD) profiles can be decoded from brain activities during naturalistic auditory experience. The study was performed on a high resolution functional magnetic resonance imaging (fMRI) dataset acquired when participants freely listened to the audio-description of the movie "Forrest Gump". Representative PSD profiles existing in the audio-movie were identified by clustering the audio samples according to their PSD descriptors. Support vector machine (SVM) classifiers were trained to differentiate the representative PSD profiles using corresponding fMRI brain activities. Based on PSD profile decoding, we explored how the neural decodability correlated to power intensity and frequency deviants. Our experimental results demonstrated that PSD profiles can be reliably decoded from brain activities. We also suggested a sigmoidal relationship between the neural decodability and power intensity deviants of PSD profiles. Our study in addition substantiates the feasibility and advantage of naturalistic paradigm for studying neural encoding of complex auditory information. PMID- 26860835 TI - Intrinsic brain subsystem associated with dietary restraint, disinhibition and hunger: an fMRI study. AB - Eating behaviors are closely related to body weight, and eating traits are depicted in three dimensions: dietary restraint, disinhibition, and hunger. The current study aims to explore whether these aspects of eating behaviors are related to intrinsic brain activation, and to further investigate the relationship between the brain activation relating to these eating traits and body weight, as well as the link between function connectivity (FC) of the correlative brain regions and body weight. Our results demonstrated positive associations between dietary restraint and baseline activation of the frontal and the temporal regions (i.e., food reward encoding) and the limbic regions (i.e., homeostatic control, including the hypothalamus). Disinhibition was positively associated with the activation of the frontal motivational system (i.e., OFC) and the premotor cortex. Hunger was positively related to extensive activations in the prefrontal, temporal, and limbic, as well as in the cerebellum. Within the brain regions relating to dietary restraint, weight status was negatively correlated with FC of the left middle temporal gyrus and left inferior temporal gyrus, and was positively associated with the FC of regions in the anterior temporal gyrus and fusiform visual cortex. Weight status was positively associated with the FC within regions in the prefrontal motor cortex and the right ACC serving inhibition, and was negatively related with the FC of regions in the frontal cortical-basal ganglia-thalamic circuits responding to hunger control. Our data depicted an association between intrinsic brain activation and dietary restraint, disinhibition, and hunger, and presented the links of their activations and FCs with weight status. PMID- 26860836 TI - [Gastroduodenal and rectal neuroendocrine neoplasms. When endoscopic and when surgical therapy?]. PMID- 26860837 TI - Teaching ultrasound-guided regional anesthesia remotely: a feasibility study. AB - BACKGROUND: Ultrasound-guided regional anesthesia (UGRA) requires acquisition of new skills. Learning requires one-on-one teaching, and can be limited by time and mentor availability. We investigate whether the skills required for UGRA can be developed and subsequently assessed remotely using a novel online teaching platform. This platform was developed at the University of Toronto to teach laparoscopic surgery remotely and has been termed Telesimulation. METHODS: Anesthesia Site Chiefs at 10 hospitals across Ontario were sent a letter inviting their anesthesia teams to participate in an UGRA remote training program. Four to five anesthetists from each site were recruited from the first four hospitals expressing interest. Simulation models and ultrasound machines were set up at each location and connected via Skype(TM) and web cameras with the Telesimulation center at our hospital. Training consisted of four online sessions and one offline lecture in order to teach an ultrasound-guided supraclavicular block. Participants were evaluated before and after training by on-site and off-site assessors using a validated Checklist and Global Rating Scale (GRS). RESULTS: Nineteen staff anesthetists were recruited. Post-training scores were significantly higher across both assessment tools, on-site (P < 0.001) and off site training locations (P = 0.003). The inter-rater reliability between on-site and remote training site ratings was good for the Checklist (ICC = 0.672, 95% CI: 0.369-0.830) and excellent for the GRS (ICC = 0.847, 95% CI: 0.706-0.921). CONCLUSION: This study demonstrates that UGRA can be taught remotely. Future research will focus on comparing this method to on-site teaching and its application in resource-restricted countries. PMID- 26860839 TI - Improved survival in patients enrolled promptly into remote monitoring following cardiac implantable electronic device implantation. AB - PURPOSE: Guidelines advocate remote monitoring (RM) in patients with a cardiac implantable electronic device (CIED). However, it is not known when RM should be initiated. We hypothesized that prompt initiation of RM (within 91 days of implant) is associated with improved survival compared to delayed initiation. METHODS: This retrospective, national, observational cohort study evaluated patients receiving new implants of market-released St. Jude MedicalTM pacemakers (PM), implantable cardioverter defibrillators (ICD), and cardiac resynchronization therapy (CRT) devices. Patients were assigned to one of two groups: an "RM Prompt" group, in which RM was initiated within 91 days of implant; and an "RM Delayed" group, in which RM was initiated >91 days but <=365 days of implant. The primary endpoint was all-cause mortality. RESULTS: The cohort included 106,027 patients followed for a mean of 2.6 +/- 0.9 years. Overall, 47,014 (44 %) patients had a PM, 31,889 (30 %) patients had an ICD, 24,005 (23 %) patients had a CRT-D, and 3119 (3 %) patients had a CRT-P. Remote monitoring was initiated promptly (median 4 weeks [IQR 2, 8 weeks]) in 66,070 (62 %) patients; in the other 39,957 (38 %) patients, RM initiation was delayed (median 24 weeks [IQR 18, 34 weeks]). In comparison to delayed initiation, prompt initiation of RM was associated with a lower mortality rate (4023 vs. 4679 per 100,000 patient-years, p < 0.001) and greater adjusted survival (HR 1.18 [95 % CI 1.13-1.22], p < 0.001). CONCLUSIONS: Our data, for the first time, show improved survival in patients enrolled promptly into RM following CIED implantation. This advantage was observed across all CIED device types. PMID- 26860838 TI - Prospective randomized comparison of rotational angiography with three dimensional reconstruction and computed tomography merged with electro-anatomical mapping: a two center atrial fibrillation ablation study. AB - PURPOSE: To compare the efficacy and accuracy of rotational angiography with three-dimensional reconstruction (3DATG) image merged with electro-anatomical mapping (EAM) vs. CT-EAM. METHODS: A prospective, randomized, parallel, two center study conducted in 36 patients (25 men, age 65 +/- 10 years) undergoing AF ablation (33 % paroxysmal, 67 % persistent) guided by 3DATG (group 1) vs. CT (group 2) image fusion with EAM. 3DATG was performed on the Philips Allura Xper FD 10 system. Procedural characteristics including time, radiation exposure, outcome, and navigation accuracy were compared between two groups. RESULTS: There was no significant difference between the groups in total procedure duration or time spent for various procedural steps. Minor differences in procedural characteristics were present between two centers. Segmentation and fusion time for 3DATG or CT-EAM was short and similar between both centers. Accuracy of navigation guided by either method was high and did not depend on left atrial size. Maintenance of sinus rhythm between the two groups was no different up to 24 months of follow-up. CONCLUSION: This study did not find superiority of 3DATG EAM image merge to guide AF ablation when compared to CT-EAM fusion. Both merging techniques result in similar navigation accuracy. PMID- 26860840 TI - Immunopathological assessments of human Blastocystis spp. in experimentally infected immunocompetent and immunosuppresed mice. AB - Blastocystis spp., one of the most common parasites colonizing the human intestine, is an extracellular, luminal protozoan with controversial pathogenesis. The host's immune response against Blastocystis spp. infection has also not been defined yet. Therefore, this research aimed to assess the potential pathogenicity of this parasite and its ability to modulate the immune response in experimental infected immunocompetent and immunosuppresed mice. These results demonstrated that the infected immunosuppressed mice were more affected than infected immunocompetent mice. Histopathological examination of the small intestine in the infected immunosuppressed mice showed that Blastocystis spp. infiltrated all the layers. Moreover, the epithelia showed exfoliation and inflammatory cell infiltration in submucosa compared to that of the infected immunocompetent mice. As well, examination of the large intestine of the infected immunosuppressed group showed severe goblet cell hyperplasia. Blastocystis spp. infiltrated all the large intestine layers compared to that of the infected immunocompetent group. Furthermore, there was a significant upregulation of the expression of proinflammatory cytokines: interleukin 12 (IL-12) and tumor necrosis factor alpha (TNF-alpha) in the infected immunosuppressed mice compared to that of the infected immunocompetent ones (p <= 0.004 and p <= 0.002, respectively). However, the expression of anti-inflammatory cytokines (IL-4 and IL-10) was significantly downregulated in the infected immunosuppressed group compared to that of the infected immunocompetent group one at 10 days postinfection (p <= 0.002 and p <= 0.001, respectively). The results of this study revealed that Blastocystis spp. affected the production of pro- and anti inflammatory cytokines in both groups of mice compared to healthy normal (naive) group. Additionally, these data showed that there was a significant upregulation (p <= 0.005) of the locally synthesized antibody: secretary IgA (sIgA) in the gut of the infected immunocompetent mice when compared to that of the infected immunosuppressed ones. PMID- 26860841 TI - Investigating the compatibility of the biocontrol agent Clonostachys rosea IK726 with prodigiosin-producing Serratia rubidaea S55 and phenazine-producing Pseudomonas chlororaphis ToZa7. AB - This study was carried out to assess the compatibility of the biocontrol fungus Clonostachys rosea IK726 with the phenazine-producing Pseudomonas chlororaphis ToZa7 or with the prodigiosin-producing Serratia rubidaea S55 against Fusarium oxysporum f. sp. radicis-lycopersici. The pathogen was inhibited by both strains in vitro, whereas C. rosea displayed high tolerance to S. rubidaea but not to P. chlororaphis. We hypothesized that this could be attributed to the ATP-binding cassette (ABC) proteins. The results of the reverse transcription quantitative PCR showed an induction of seven genes (abcB1, abcB20, abcB26, abcC12, abcC12, abcG8 and abcG25) from subfamilies B, C and G. In planta experiments showed a significant reduction in foot and root rot on tomato plants inoculated with C. rosea and P. chlororaphis. This study demonstrates the potential for combining different biocontrol agents and suggests an involvement of ABC transporters in secondary metabolite tolerance in C. rosea. PMID- 26860842 TI - Relationship between in vitro characterization and comparative efficacy of plant growth-promoting rhizobacteria for improving cucumber salt tolerance. AB - Phosphate solubilization, 1-aminocyclopropane-1-carboxylic acid (ACC)-deaminase activity and production of siderophores and indole acetic acid (IAA) are well known traits of plant growth-promoting rhizobacteria (PGPR). Here we investigated the expression of these traits as affected by salinity for three PGPR strains (Pseudomonas fluorescens, Bacillus megaterium and Variovorax paradoxus) at two salinity levels [2 and 5 % NaCl (w/v)]. Among the three strains, growth of B. megaterium was the least affected by high salinity. However, P. fluorescens was the best strain for maintaining ACC-deaminase activity, siderophore and IAA production under stressed conditions. V. paradoxus was the least tolerant to salts and had minimal growth and low PGPR trait expression under salt stress. Results of experiment examining the impact of bacterial inoculation on cucumber growth at three salinity levels [1 (normal), 7 and 10 dS m(-1)] revealed that P. fluorescens also had good rhizosphere competence and was the most effective for alleviating the negative impacts of salinity on cucumber growth. The results suggest that in addition to screening the PGPR regarding their effect on growth under salinity, PGPR trait expression is also an important aspect that may be useful for selecting the most promising PGPR bacterial strains for improving plant tolerance to salinity stress. PMID- 26860843 TI - Sensitive methods for screening of the MEK1 gene mutations in patients with central nervous system metastases of non-small cell lung cancer. AB - BACKGROUND: The mitogen-activated protein kinases 1 and 2 (MEK1, MEK2) are fundamental partners in the RAS-RAF-MEK-ERK pathway that is involved in regulation of cell proliferation, differentiation and survival. Downregulation of the MEK cascades has been implicated in acquiring of the malignant phenotype in various cancers. Somatic mutations in MEK1 gene (substitutions K57N, Q56P, D67N) were described in <1 % of non-small cell lung cancer (NSCLC) and they were more commonly reported in adenocarcinoma patients with current or former smoking status. MATERIALS AND METHODS: In the following study, we assessed the MEK1 gene mutations in 145 FFPE tissue samples from central nervous system (CNS) metastases of NSCLC using HRM-PCR and ASP-qPCR techniques. The studied group was heterogeneous in terms of histopathology and smoking status. The prevalence of the MEK1 gene mutation was correlated with the occurrence of mutations in KRAS, EGFR, DDR2, PIK3CA, NRAS, HER2, AKT1 and PTEN genes. RESULTS: Using HRM and ASP qPCR methods we identified one (0.7 %; 1/145) MEK1 substitution (Q56P) in CNS metastases of NSCLC. The mutation was identified in a single, 50-year-old, current smoking men with adenocarcinoma (1.25 %; 1/80 of all adenocarcinomas). CONCLUSIONS: According to the current knowledge, the incidence of MEK1 gene mutation in CNS metastatic lesion of NSCLC is the first such report worldwide. The analysis of gene profile in cancer patients may extend the scope of molecularly targeted therapies used both in patients with primary and metastatic tumors of NSCLC. PMID- 26860844 TI - Postoperative Respiratory Exercises Reduce the Risk of Developing Pulmonary Complications in Patients Undergoing Lobectomy. AB - OBJECTIVE: To evaluate the effects of an intensive postoperative physiotherapy program focused on respiratory exercises in patients undergoing lobectomy by open thoracotomy. DESIGN: Quasi-experimental study. SETTING: Tertiary referral academic hospital. PARTICIPANTS: 208 patients undergoing lobectomy by open thoracotomy. INTERVENTIONS: Control group patients (n=102) received standard medical/nursing care, and experimental group patients (n=106) added to the standard clinical pathway a daily physiotherapy program focused on respiratory exercises until discharge. OUTCOMES: Analyzed outcomes were the frequency of postoperative pulmonary complications (PPCs) more amenable to physiotherapy (pneumonia, atelectasis and respiratory insufficiency) and length of hospital stay (LOS). RESULTS: Both groups were comparable regarding preoperative and surgical characteristics. Incidence of PPCs was 20.6% in control and 6.6% in experimental group (P=.003). Median (IQR) LOS in control group was 14 (7) days (Huber M estimator 14.21) and 12 (6) days (Huber M estimator 12.81) in experimental. Logistic regression model identified the evaluated physiotherapy program (P=.017; EXP [B] 95% CI 0.081-0.780) and % FEV1 (P=.042; EXP [B] 95% CI 0.941-0.999) as protective factors for the development of PPCs in patients undergoing lobectomy. CONCLUSIONS: Implementing a postoperative intensive physiotherapy program focused on respiratory exercises reduces the risk of PPCs and resultant LOS on patients undergoing lobectomy. PMID- 26860845 TI - [Global health of unaccompanied refugee minors in Gironde (France) between 2011 and 2013]. AB - The lack of clinical practice recommendations for the care of the Unaccompanied Refugee Minors (URM) causes significant disparities depending on which department they arrive. By studying their global health we're willing to promote a standard of care for them. METHODS: Data descriptive study from a systematic medical procedure proposed to URM who came in Gironde between January, 2011 and December, 2013. RESULTS: 235 URM were included, from Africa (71%), Asia (21%) and from Eastern Europe (8%). Among them, 143 medical files were complete. The most frenquently diagnosed diseases, and/or the most serious, were digestive parasitoses (50%), schistosomiasis (7%), filariasis (6%), hepatitis B (chronic 6%, seroprevalence 28%), iron deficiency (26%, 4 % with anaemia), G6PD deficiency (8%) and tooth decays (29%). About mental disorders, 45% of the URM had a clinical presentation compatible with post-traumatic stress disorder, 4% had suicidal thoughts. CONCLUSION: URM accumulate the health risks of teenagers and those of illegal immigrants. Consequently they require an oriented and particular care. PMID- 26860846 TI - Modified CLIP with objective liver reserve assessment retains prognosis prediction for patients with advanced hepatocellular carcinoma. AB - BACKGROUND AND AIM: The Cancer of the Liver Italian Program (CLIP) score is a commonly used staging system for hepatocellular carcinoma (HCC) helpful with predicting prognosis of advanced HCC. CLIP uses the Child-Turcotte-Pugh (CTP) score to evaluate liver reserve. A new scoring system, the albumin-bilirubin (ALBI) grade, has been proposed as they objectively evaluate liver reserve. We examined whether the modification of CLIP with ALBI retained its prognosis prediction for patients with advanced HCC. METHODS: We included patients who received first-line antiangiogenic therapy for advanced HCC. Liver reserve was assessed using CTP and ALBI scores, which were then incorporated into CLIP and ALBI-CLIP, respectively. To assess their efficacies of prognostic prediction, the Cox's proportional hazard model and concordance indexes were used. RESULTS: A total of 142 patients were included; 137 of them were classified CTP A and 5 patients CTP B. Patients could be divided into four or five groups with different prognosis according to CLIP and ALBI-CLIP, respectively. Higher R(2) (0.249 vs 0.216) and lower Akaike information criterion (995.0 vs 1001.1) were observed for ALBI-CLIP than for CLIP in the Cox's model predicting overall survival. ALBI-CLIP remained an independent predictor for overall survival when CLIP and ALBI-CLIP were simultaneously incorporated in Cox's models allowing variable selection with adjustment for hepatitis etiology, treatment, and performance status. The concordance index was also higher for ALBI-CLIP than for CLIP (0.724 vs 0.703). CONCLUSIONS: Modification of CLIP scoring with ALBI, which objectively assesses liver reserve, retains and might have improved prognosis prediction for advanced HCC. PMID- 26860847 TI - Letter to the editor: no increased febrile neutropenia risk to cancer patients receiving lipegfilgrastim--correction of a systematic review and meta-analysis of randomized controlled trials with G-CSF. PMID- 26860848 TI - White matter alterations in cocaine users are negatively related to the number of additionally (ab)used substances. AB - Diffusion tensor imaging studies have provided evidence for white matter (WM) alterations in cocaine users. While polysubstance use is a widespread phenomenon among cocaine users, its role in WM alterations in cocaine users is currently unknown. This study examined the relation between the number of substances that are used(cocaine, alcohol and marijuana) and WM alterations in 67 male non-drug users and 67 male regular cocaine users, who were classified into five groups based on the number of used substances. Diffusion-weighted images were acquired on a 3.0 T magnetic resonance imaging scanner. Using tract-based spatial statistics we demonstrated that there was a negative relation between the number of used substances and fractional anisotropy, a global measure of WM integrity. Also, we demonstrated a positive relation between the number of used substance and radial diffusivity within the prefrontal lobe, suggesting an increase in demyelination with the number of used substances. We did not find a dose-effect between the level of substance use and WM alterations. The results of the current study may reflect the presence of a pre-existing vulnerability to polysubstance use resulting from prefrontal WM abnormalities and related impaired cognitive control although WM alterations because of polysubstance use cannot be fully excluded. This study is an important first step in understanding the problems related to polysubstance use among cocaine users. PMID- 26860850 TI - De novo development of a cerebral arteriovenous malformation following radiation therapy: Case report and an update to classical arteriovenous malformation nomenclature. AB - Cerebral arteriovenous malformations (AVM) are traditionally considered primary congenital lesions that result from embryological aberrations in vasculogenesis. Recent insights, however, suggest that these lesions may be secondary to a vascular insult such as ischemia or trauma. Herein, the authors present a rare case of a secondary cerebral AVM, occurring in a young girl who received prior cranial radiation therapy. At age 3years, she underwent surgical resection, chemotherapy, and photon radiation therapy for treatment of a fourth ventricular ependymoma. At age 19years, she developed new onset seizures and was found to have a left medial temporal lobe AVM. Her seizures were managed successfully with anti-epileptic medications and the AVM was treated with proton radiation therapy. This case highlights a rare but possible vascular sequela of radiation therapy and adds to the growing body of evidence that cerebral AVM may arise as secondary lesions. PMID- 26860849 TI - A restrictive policy for red blood cell transfusion in older hip fracture patients: experiences from a patient register. AB - BACKGROUND: Allogeneic red blood cell transfusions (ABT) are common in older hip fracture patients. Recent research supports a restrictive transfusion policy. The aim was to study variation in hemoglobin (Hb) concentration, and clinical outcomes in these patients. RESULTS: Cross-sectional study with one-year follow up in an orthogeriatric unit. Data were obtained from a quality register with demographic and medical information collected by an interdisciplinary team. 106 (22 %) of the 491 patients admitted from September 2011 throughout September 2012 (76 % women, mean age 85 years) received ABT. When given ABT, 80 % had Hb <80 g/l and mean Hb was 78 g/l. Mean Hb, regardless ABT, showed variation from 125 g/l (+/-16) on admission to 106 g/l (+/-17), 101 g/l (+/-16) and 102 g/l (+/-14) on 1st, 3rd and 5th postoperative day respectively. Patients with per /subtrochanteric fractures more often received ABT than those with femur neck fractures (p < 0.001), 70 % of the patients receiving ABT had a per /subtrochanteric fracture. Patients who received ABT were older, had more chronic diseases and lower mean Hb throughout the hospital stay. Length of stay was longer (median 7 vs. 6 days, p = 0.01), and medical complications more common. In hospital and 30-day mortalities were similar in patients given ABT and in those who were not, but 1-year mortality was higher among patients who were given ABT (p = 0.008). CONCLUSIONS: Hb had a tendency to fall during the three first days after surgery and seemed to be stabilized on day 5. Patients who received ABT had poorer health, but not significantly higher short-term mortality. This study demonstrates a restrictive transfusion policy. PMID- 26860851 TI - Communicating the diagnosis of psychogenic nonepileptic seizures: The patient perspective. AB - Psychogenic nonepileptic seizures (PNES) are a common cause of refractory seizures. Video-electroencephalographic (EEG) monitoring has allowed PNES to be effectively distinguished from epileptic seizures. Once the diagnosis of PNES is established, neurologists face the challenge of explaining it to patients. Patients may not always receive the diagnosis well. The aim of this study is to evaluate how effectively patients receive and perceive the diagnosis of PNES. This prospective study was conducted in an eight-bed epilepsy monitoring unit (EMU). Adult patients with newly confirmed PNES were included. After receiving written consent, a self-administered questionnaire was given to patients after the attending physician had communicated the diagnosis of PNES. A total of 75 patients were recruited. All patients had their typical seizures recorded on video-EEG (range 1-12, mean 2.18). Seventy patients were satisfied with the diagnosis of PNES. Nine patients did not agree that PNES has a psychological cause. Nineteen patients thought that the EMU doctors had no clue as to the cause of their seizures and 20 thought that there was no hope for a cure of their seizures. A significant number of patients with PNES feel that there is no hope for cure of their seizures. Thorough education about PNES, properly preparing patients before discussing the diagnosis of PNES, and preferably earlier diagnosis may prevent this miscommunication and result in better outcomes. A comprehensive approach including psychological counseling and psychiatric input, evaluation and treatment, in order to bring the illness from the subconscious to the conscious level, and effective follow-up may be helpful. PMID- 26860852 TI - Underlying Mechanisms of Zymographic Diversity in Starch Synthase I and Pullulanase in Rice-Developing Endosperm. AB - Amylopectin is synthesized by the coordinated actions of many (iso)enzymes, including ADP-glucose pyrophosphorylase (AGPase), starch synthases (SSs), branching enzymes (BEs), and debranching enzymes (DBEs). Here, two polymorphic forms of starch synthase I (SSI) and pullulanase (PUL) in rice-developing seeds, designated as SSI-1/SSI-2 and PUL-1/PUL-2, were discovered for the first time by zymographic analysis. The SSI and PUL polymorphisms were strongly associated with the SSI microsatellite marker (p = 3.6 * 10(-37)) and PUL insertion/deletion (InDel) markers (p < 3.6 * 10(-51)). Western blotting and mass spectrometric analysis confirmed that the polymorphic bands were truly the SSI and PUL enzymes. Only one non-synonymous variation in SSI DNA sequence (the SNP A/G) causing the change of the amino acid K438 to E438 was observed, which coincided well with the polymorphic forms of SSI. Nine non-synonymous variations were found between PUL-1 and PUL-2. Two non-synonymous variations of PUL (F316L and D770E) were identified by mass spectrometric analysis, but all of the variations did not change the structure of PUL. The co-immunoprecipitation results revealed the differences in protein-protein interaction patterns, i.e., strong or weaker signals of SSI-BEI and SSI-BEIIb, between the two forms of SSI. The results will enhance our understanding of SSI and PUL properties and provide helpful information to understand their functions in starch biosynthesis in rice endosperm. PMID- 26860853 TI - Longitudinal Use of Micro-computed Tomography Does Not Alter Microarchitecture of the Proximal Tibia in Sham or Ovariectomized Sprague-Dawley Rats. AB - In vivo micro-computed tomography (MUCT) provides the ability to measure longitudinal changes to tibia microarchitecture, but the effect of this radiation is not well understood. The right proximal tibia of Sprague-Dawley rats (n = 12/group) randomized to Sham-control (Sham) or ovariectomy (OVX) surgery at 12 weeks of age was scanned using MUCT at 13, 17, 21, and 25 weeks of age, at a resolution of 18 MUm and a radiation dose of 603 mGy. The left proximal tibia was scanned only at 25 weeks of age to serve as an internal non-irradiated control. Repeated irradiation did not affect tibia microarchitecture in Sham or OVX groups, although there was an increase in cortical eccentricity (P < 0.05). All trabecular outcomes and cortical BMD were different (P < 0.05) between groups after only 1 week post-surgery and differences persisted to study endpoint. Characteristic changes to trabecular bone were observed in OVX rats over time. Interactions of time and hormone status were found for cortical BMD (P < 0.001), Ps. Pm., and Ec. Pm. (P < 0.05). Repeated irradiation of the tibia at 13, 17, 21, and 25 weeks does not cause adverse effects to microarchitecture, regardless of hormone status. This radiation dose can be applied over a typical 3-month study period to comprehensively understand how an intervention alters tibia microarchitecture without confounding effects of radiation. PMID- 26860858 TI - CAR T-cell therapy: opportunities and challenges. AB - A letter in response to: Milena Kalaitsidou, Gray Kueberuwa, Antje Schutt & David Edward Gilham. CAR T-cell therapy: toxicity and the relevance of preclinical models. Immunotherapy 7(5), 487-497 (2015). PMID- 26860859 TI - Interviews with Irish healthcare workers from different disciplines about palliative care for people with Parkinson's disease: a definite role but uncertainty around terminology and timing. AB - BACKGROUND: An integrated palliative care approach is recommended in all life limiting diseases, including Parkinson's disease (PD). However research shows that people with PD have unmet palliative care needs. The study aimed to explore multidisciplinary healthcare workers' (HCWs) views on palliative care for people with PD, identifying perceived barriers and facilitators. METHODS: A qualitative design was used; data was analysed using Thematic Analysis. Semi-structured interviews were conducted with 30 HCWs, working either with people with PD or in a palliative care setting in Ireland. RESULTS: A number of perceived barriers were evident helping to account for the previously reported unmet palliative care needs in PD. A lack of education about PD and palliative care meant that HCWs were unsure of the appropriateness of referral, and patients and carers weren't equipped with information to seek palliative care. A lack of communication between PD and palliative care specialists was seen to impede collaboration between the disciplines. Uncertainty about the timing of palliative care meant that it was often not introduced until a crisis point, despite the recognised need for early planning due to increased prevalence of dementia. CONCLUSIONS: Most HCWs recognised a need for palliative care for people with PD; however several barriers to implementing a palliative care approach in this population need to be addressed. Implications for clinical practice and policy include the need for an integrated model of care, and education for all HCWs, patients, carers, and the public on both the nature of advanced PD, and the potential of palliative care in support of patients and their family members. PMID- 26860861 TI - Effect of anticoagulation on cardioembolic stroke severity, outcomes and response to intravenous thrombolysis. AB - Our objective was to evaluate the effect of anticoagulation on cardioembolic stroke (CS) severity, outcomes, and response to intravenous thrombolysis (IVT). Observational study of CS patients admitted to a Stroke Center (2010-2013). The sample was classified into three groups based on pre-stroke oral anticoagulants (OAC) treatment (all acenocumarol) and the international normalized ratio (INR) on admission: (1) non-anticoagulated or anticoagulated patients with INR <1.5, (2) anticoagulated with INR 1.5-1.9 and (3) anticoagulated with INR >=2. We compared demographic data, vascular risk factors, symptomatic intracranial hemorrhage, severity on admission (NIHSS) and 3 month outcomes (mRS). Overall 475 patients were included, 47.2 % male, mean age 75.5 (SD 10.7) years old, 31.8 % were on OAC. 76 % belonged to the INR <1.5 group, 13.3 % to the INR 1.5-1.9 and 10.5 % to the INR >2. 35 %of patients received IVT. Multivariate analyses showed that an INR >=2 on admission was a factor associated with a higher probability of mild stroke (NIHSS <10) (OR 2.026, 95 % CI 1.006-4.082). Previous OAC in general (OR 2.109, 95 % CI 1.173-3.789) as well as INR 1.5-1.9 (OR 3.676, 95 % CI 1.510 8.946) were associated with favorable outcomes (mRS <=2). OAC was not related to stroke outcomes in the subgroup of IVT patients. Therapeutic OAC levels are associated with lesser CS severity, and prior OAC treatment with favorable outcomes. In this study, OAC are not related with response to IVT. PMID- 26860862 TI - The 37 item Version of the Mini-Mental State Examination: Normative Data in a Population-Based Cohort of Older Spanish Adults (NEDICES). AB - The 37-item version of the Mini-Mental State Examination (MMSE-37) is an extended version of the original test for individuals with low education, which was adapted for different cultures. Despite its favorable psychometric properties, there is a lack of normative data for this instrument. We provide normative data for the MMSE-37 stratified by age, sex, and education in a large population-based cohort of older Spanish adults. The sample consisted of 3,777 participants without dementia (age range: 65-97 years) from different socioeconomic areas of central Spain. Normative data are presented in percentile ranks and divided into nine overlapping age tables with different midpoints, using the overlapping cell procedure. A hierarchical regression was performed to evaluate the effects of sociodemographic variables on MMSE-37 performance. Results showed that age, sex, and education affect test score. The norms presented herein are important for the correct interpretation of MMSE-37 scores when assessing older adults in Spain. PMID- 26860863 TI - Early reversal cells in adult human bone remodeling: osteoblastic nature, catabolic functions and interactions with osteoclasts. AB - The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts. Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) 3/4-collagen fragments typically generated by extracellular collagenases of the MMP family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic. PMID- 26860864 TI - Disentangling the aneuploidy and senescence paradoxes: a study of triploid breast cancers non-responsive to neoadjuvant therapy. AB - Aneuploid cells should have a reduced proliferation rate due to difficulty in proceeding through mitosis. However, contrary to this, high aneuploidy is associated with aggressive tumour growth and poor survival prognosis, in particular in triploid breast cancer. A further paradox revolves around the observation that, while cell senescence should inhibit proliferation, the senescence marker p16INK4a correlates with poor treatment outcome in patients with a very aggressive triple-negative breast carcinoma (TNBC). In this study, we aim to pour light on the possible relationship of these conundrums with polyploidy of tumour cells. We performed detailed analysis of DNA histogram profiles in diagnostic core biopsies of 30 cases of operable breast cancer and found that near triploidy in TNBC and other forms correlated with weak or no response to neoadjuvant chemotherapy (NAC) as scored by Miller-Payne index. Polyploid cells in operation samples from tumours that were non-responsive to NAC treatment were Ki67 and CD44 positive. In addition, polyploid cells were positive for markers of embryonic stemness (OCT4, SOX2, NANOG) and senescence (p16INK4a). The relationship patterns between p16INK4a and NANOG were heterogeneous, with predominantly mutually exclusive expression but also synergistic and intermediate variants in the same samples. We conclude that the aneuploidy and senescence paradoxes can be explained by the mutual platform of polyploidy, conferring genomic and epigenetic instability as a survival advantage. Such cells are able to bypass aneuploidy restrictions of conventional mitosis and overcome the barrier of senescence by a shift to self-renewal, resulting in progression of cancer. PMID- 26860866 TI - Expression of area-specific M2-macrophage phenotype by recruited rat monocytes in duct-ligation pancreatitis. AB - Acute pancreatitis remains a disease of uncertain pathogenesis and no established specific therapy. Previously, we found a predominant increase and active proliferation of macrophages in the inflamed tissues of a rat duct-ligation pancreatitis model. To analyze the origin and possible role of these macrophages, we investigated their in situ cellular kinetics in a rat model of duct-ligation pancreatitis using a recently established method of multicolor immunostaining for macrophage markers and for proliferating cells with ethynyl deoxyuridine. To detect monocyte-derived macrophages, green fluorescent protein-transgenic (GFP(+)) leukocytes were transferred to monocyte-depleted recipients. In the inflamed pancreas, infiltrating macrophages were mainly two phenotypes, CD68(+)CD163(-) round cells and CD68(+)CD163(+) large polygonal cells, both of which showed active proliferation. In the interlobular area, the proportions of CD68(+)CD163(low) and CD68(+)CD163(high) cells increased over time. Most expressed the M2-macrophage markers CD206 and arginase 1. In contrast, in the interacinar area, CD68(+) cells did not upregulate CD163 and CD206, but ~30 % of them expressed the M1 marker nitric oxide synthase 2 on day 4. GFP(+)-recruited cells were primarily CD68(+)CD163(-) monocytes on day 1 and showed phenotypic changes similar to those of the monocyte non-depleted groups. In conclusion, infiltrating macrophages mostly formed two distinct subpopulations in different areas: monocyte-derived macrophages with the M2 phenotype in the interlobular area or non-M2 phenotype in the interacinar area. Involvement of resident macrophages might be minor in this model. These results are the first demonstration of an upregulated M2 phenotype in rat inflammatory monocytes, which may promote tissue repair. PMID- 26860865 TI - Facioscapulohumeral dystrophy myoblasts efficiently repair moderate levels of oxidative DNA damage. AB - Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy linked to a deletion of a subset of D4Z4 macrosatellite repeats accompanied by a chromatin relaxation of the D4Z4 array on chromosome 4q. In vitro, FSHD primary myoblasts show altered expression of oxidative-related genes and are more susceptible to oxidative stress. Double homeobox 4 (DUX4) gene, encoded within each D4Z4 unit, is normally transcriptionally silenced but is found aberrantly expressed in skeletal muscles of FSHD patients. Its expression leads to a deregulation of DUX4 target genes including those implicated in redox balance. Here, we assessed DNA repair efficiency of oxidative DNA damage in FSHD myoblasts and DUX4-transfected myoblasts. We have shown that the DNA repair activity is altered neither in FSHD myoblasts nor in immortalized human myoblasts transiently expressing DUX4. DNA damage caused by moderate doses of an oxidant is efficiently repaired while FSHD myoblasts exposed for 24 h to high levels of oxidative stress accumulated more DNA damage than normal myoblasts, suggesting that FSHD myoblasts remain more vulnerable to oxidative stress at high doses of oxidants. PMID- 26860867 TI - New Approach for Inhibition of HIV Entry: Modifying CD4 Binding Sites by Thiolated Pyrimidine Derivatives. AB - Thiolated pyrimidine derivatives have been synthetized and their antiretroviral effect against human immunodeficiency virus type 1 (HIV-1IIIB) and HIV-1 chimeric pseudovirions have been quantitatively determined in cell-based viral infectivity assays including syncytium inhibition assay as well as a single-cycle viral infection assay on HeLaCD4-LTR/beta-gal cells. Pseudotype virions prepared bearing HIV-1 envelope preference for CCR5 coreceptor, CXCR4 coreceptor or for both, respectively, with a HIV-1 core containing luciferase reporter gene were able to infect susceptible cells but are replication defective so unable to replicate in the cells . Data indicate that thiolated pyrimidine derivatives inhibited effectively virally induced cell fusion in vitro as well as infectivity of primary HIV-1IIIB strain and HIV-1 pseudovirions using chemokine receptors CCR5 or CXCR4 or both for virus entry a dose dependent manner. Inhibition was selective, depended on the pseudovirus coreceptor preference. Our results suggest that some of these sulfur containing pyrimidines interact with redoxactive -SH groups required for successful HIV entry, including a redox active disulfide in the CD4 molecule as well as -SH groups in HIV viral envelope gp120. This mode of action is unique representing a new class of potential HIV entry inhibitors. PMID- 26860868 TI - Sialendoscopy-assisted transfacial surgery for the removal of an iatrogenic foreign body in Stensen's duct: a stone and broken wire basket. AB - BACKGROUND: A foreign body is a rare cause of parotid gland obstructive sialadenitis; intra-oral penetration via Stensen's duct is unusual. The relatively recent introduction of interventional sialendoscopy to treat obstructive sialadenitis has allowed surgeons to adopt a gland-sparing approach by means of miniaturised endoscopes and instruments. However, unusual anatomy or pathological conditions can give rise to a risk of intraductal rupture that may lead to a subsequent iatrogenic foreign body. CASE REPORT: This paper describes the case of a patient with a 4 mm stone engaged by a broken wire basket stuck in a secondary branch of Stensen's duct. RESULTS: The iatrogenic foreign body was successfully retrieved by means of sialendoscopy-assisted transfacial surgery. CONCLUSION: This is the first reported case of an intraductal rupture of a miniaturised device during interventional sialendoscopy successfully resolved by means of combined endoscopy and external surgery. This proved to be an effective method of rescuing a foreign body stuck in Stensen's duct. PMID- 26860869 TI - Natural selection in a population of Drosophila melanogaster explained by changes in gene expression caused by sequence variation in core promoter regions. AB - BACKGROUND: Understanding the evolutionary forces that influence variation in gene regulatory regions in natural populations is an important challenge for evolutionary biology because natural selection for such variations could promote adaptive phenotypic evolution. Recently, whole-genome sequence analyses have identified regulatory regions subject to natural selection. However, these studies could not identify the relationship between sequence variation in the detected regions and change in gene expression levels. We analyzed sequence variations in core promoter regions, which are critical regions for gene regulation in higher eukaryotes, in a natural population of Drosophila melanogaster, and identified core promoter sequence variations associated with differences in gene expression levels subjected to natural selection. RESULTS: Among the core promoter regions whose sequence variation could change transcription factor binding sites and explain differences in expression levels, three core promoter regions were detected as candidates associated with purifying selection or selective sweep and seven as candidates associated with balancing selection, excluding the possibility of linkage between these regions and core promoter regions. CHKov1, which confers resistance to the sigma virus and related insecticides, was identified as core promoter regions that has been subject to selective sweep, although it could not be denied that selection for variation in core promoter regions was due to linked single nucleotide polymorphisms in the regulatory region outside core promoter regions. Nucleotide changes in core promoter regions of CHKov1 caused the loss of two basal transcription factor binding sites and acquisition of one transcription factor binding site, resulting in decreased gene expression levels. Of nine core promoter regions regions associated with balancing selection, brat, and CG9044 are associated with neuromuscular junction development, and Nmda1 are associated with learning, behavioral plasticity, and memory. Diversity of neural and behavioral traits may have been maintained by balancing selection. CONCLUSIONS: Our results revealed the evolutionary process occurring by natural selection for differences in gene expression levels caused by sequence variation in core promoter regions in a natural population. The sequences of core promoter regions were diverse even within the population, possibly providing a source for natural selection. PMID- 26860871 TI - Experimental and computational optimization of an Escherichia coli co-culture for the efficient production of flavonoids. AB - Metabolic engineering and synthetic biology have enabled the use of microbial production platforms for the renewable production of many high-value natural products. Titers and yields, however, are often too low to result in commercially viable processes. Microbial co-cultures have the ability to distribute metabolic burden and allow for modular specific optimization in a way that is not possible through traditional monoculture fermentation methods. Here, we present an Escherichia coli co-culture for the efficient production of flavonoids in vivo, resulting in a 970-fold improvement in titer of flavan-3-ols over previously published monoculture production. To accomplish this improvement in titer, factors such as strain compatibility, carbon source, temperature, induction point, and inoculation ratio were initially optimized. The development of an empirical scaled-Gaussian model based on the initial optimization data was then implemented to predict the optimum point for the system. Experimental verification of the model predictions resulted in a 65% improvement in titer, to 40.7+/-0.1mg/L flavan-3-ols, over the previous optimum. Overall, this study demonstrates the first application of the co-culture production of flavonoids, the most in-depth co-culture optimization to date, and the first application of empirical systems modeling for improvement of titers from a co-culture system. PMID- 26860870 TI - Validation of a coding algorithm for intra-abdominal surgeries and adhesion related complications in an electronic medical records database. AB - PURPOSE: Epidemiological data on adhesion-related complications following intra abdominal surgery are limited. We tested the accuracy of recording of these surgeries and complications within The Health Improvement Network (THIN), a primary care database within the UK. METHODS: Individuals within THIN from 1995 to 2011 with an incident intra-abdominal surgery and subsequent bowel obstruction (SBO) or adhesiolysis were identified using diagnostic codes. To compute positive predictive values (PPVs), requests were sent to treating physicians of patients with these diagnostic codes to confirm the surgery, SBO, or adhesiolysis code. Completeness of recording was estimated by comparing observed surgical rates within THIN to expected rates derived from the Hospital Episode Statistics dataset within England. Cumulative incidence rates of adhesion-related complications at 5 years were compared with a previously published cohort within Scotland. RESULTS: Two hundred seventeen of 245 (89%) questionnaires were returned (180 SBO and 37 adhesiolysis). The PPV of codes for surgery was 94.5% (95%CI: 91-97%). The 88.8% of procedure types were correctly coded. The PPV for SBO and adhesiolysis was 86.1% (95%CI: 80-91%) and 89.2% (95%CI: 75-97%), respectively. Colectomy, appendectomy, and cholecystectomy rates within THIN were 99%, 95%, and 84% of rates observed in national Hospital Episode Statistics data, respectively. Cumulative incidence rates of adhesion related complications following colectomy, appendectomy, and small bowel surgery were similar to those published previously. CONCLUSIONS: Surgical procedures, SBO, and adhesiolysis can be accurately identified within THIN using diagnostic codes. THIN represents a new tool for assessing patient-specific risk factors for adhesion-related complications and long-term outcomes. PMID- 26860873 TI - Long-term cognitive and school outcomes of late-preterm and early-term births: a systematic review. AB - BACKGROUND: Children born before full term (39-41 weeks' gestation) are at increased risk of adverse cognitive outcomes. Risk quantification is important as late-preterm (LPT; 34-36 weeks) and early-term (ET; 37-38 weeks) births are common. METHOD: This review analyses the effect of LPT and ET births on long-term cognitive and educational outcomes. The primary outcome was general cognitive ability. Secondary outcomes included verbal/non-verbal intelligence quotient, subject-specific school performance and special educational needs. The search strategy included Medline and Embase from January 1975 to June 2013. Eligible studies investigated specified outcomes and included suitable gestational age participants assessed at 2 years and older. Outcome measures and socio demographic descriptors were extracted, and data meta-analysed where possible. RESULTS: Eight studies compared ET birth with full-term birth. Fourteen studies compared LPT birth with either term birth (>37 weeks, n = 12 studies) or full term birth (39-41 weeks, n = 2 studies). Substantial between-study heterogeneity existed. LPT and ET children underperformed in most outcomes compared with their term/full-term counterparts, respectively. For example, LPT children had an increased risk of lower general cognitive ability (adjusted risk ratio 1.38 [95% confidence interval 1.06-1.79]), and full-term children performed 5% of a standard deviation higher (z-score 0.05 [0.02, 0.08]) than ET children. Poorer outcomes persist into adulthood; term cohorts performed 5% of a standard deviation higher than LPT cohorts (z-score 0.05 [0.04, 0.07]), and full-term cohorts performed 3% of a standard deviation higher than ET cohorts (z-score 0.03 [0.02, 0.04]). CONCLUSION: This review critically examines the knowledge around long-term cognitive outcomes of LPT and ET births, demonstrating multiple, small, adverse differences between LPT/ET and term/full-term births. PMID- 26860872 TI - Activation of zebrafish Src family kinases by the prion protein is an amyloid beta-sensitive signal that prevents the endocytosis and degradation of E cadherin/beta-catenin complexes in vivo. AB - BACKGROUND: Prions and amyloid-beta (Abeta) oligomers trigger neurodegeneration by hijacking a poorly understood cellular signal mediated by the prion protein (PrP) at the plasma membrane. In early zebrafish embryos, PrP-1-dependent signals control cell-cell adhesion via a tyrosine phosphorylation-dependent mechanism. RESULTS: Here we report that the Src family kinases (SFKs) Fyn and Yes act downstream of PrP-1 to prevent the endocytosis and degradation of E-cadherin/beta catenin adhesion complexes in vivo. Accordingly, knockdown of PrP-1 or Fyn/Yes cause similar zebrafish gastrulation phenotypes, whereas Fyn/Yes expression rescues the PrP-1 knockdown phenotype. We also show that zebrafish and mouse PrPs positively regulate the activity of Src kinases and that these have an unexpected positive effect on E-cadherin-mediated cell adhesion. Interestingly, while PrP knockdown impairs beta-catenin adhesive function, PrP overexpression enhances it, thereby antagonizing its nuclear, wnt-related signaling activity and disturbing embryonic dorsoventral specification. The ability of mouse PrP to influence these events in zebrafish embryos requires its neuroprotective, polybasic N-terminus but not its neurotoxicity-associated central region. Remarkably, human Abeta oligomers up-regulate the PrP-1/SFK/E-cadherin/beta-catenin pathway in zebrafish embryonic cells, mimicking a PrP gain-of-function scenario. CONCLUSIONS: Our gain and loss-of-function experiments in zebrafish suggest that PrP and SFKs enhance the cell surface stability of embryonic adherens junctions via the same complex mechanism through which they over-activate neuroreceptors that trigger synaptic damage. The profound impact of this pathway on early zebrafish development makes these embryos an ideal model to study the cellular and molecular events affected by neurotoxic PrP mutations and ligands in vivo. In particular, our finding that human Abeta oligomers activate the zebrafish PrP/SFK/E-cadherin pathway opens the possibility of using fish embryos to rapidly screen for novel therapeutic targets and compounds against prion- and Alzheimer's-related neurodegeneration. Altogether, our data illustrate PrP-dependent signals relevant to embryonic development, neuronal physiology and neurological disease. PMID- 26860874 TI - Health literacy: strengthening agency or changing structures? PMID- 26860877 TI - RETRACTION NOTE. PMID- 26860875 TI - The relationship between glucocerebrosidase mutations and Parkinson disease. AB - Parkinson disease (PD) is the second most common neurodegenerative disorder after Alzheimer disease, whereas Gaucher disease (GD) is the most frequent lysosomal storage disorder caused by homozygous mutations in the glucocerebrosidase (GBA1) gene. Increased risk of developing PD has been observed in both GD patients and carriers. It has been estimated that GBA1 mutations confer a 20- to 30-fold increased risk for the development of PD, and that at least 7-10% of PD patients have a GBA1 mutation. To date, mutations in the GBA1 gene constitute numerically the most important risk factor for PD. The type of PD associated with GBA1 mutations (PD-GBA1) is almost identical to idiopathic PD, except for a slightly younger age of onset and a tendency to more cognitive impairment. Importantly, the pathology of PD-GBA1 is identical to idiopathic PD, with nigral dopamine cell loss, Lewy bodies, and neurites containing alpha-synuclein. The mechanism by which GBA1 mutations increase the risk for PD is still unknown. However, given that clinical manifestation and pathological findings in PD-GBA1 patients are almost identical to those in idiopathic PD individuals, it is likely that, as in idiopathic PD, alpha-synuclein accumulation, mitochondrial dysfunction, autophagic impairment, oxidative and endoplasmic reticulum stress may contribute to the development and progression of PD-GBA1. Here, we review the GBA1 gene, its role in GD, and its link with PD. The impact of glucocerebrosidase 1 (GBA1) mutations on functioning of endoplasmic reticulum (ER), lysosomes, and mitochondria. GBA1 mutations resulting in production of misfolded glucocerebrosidase (GCase) significantly affect the ER functioning. Misfolded GCase trapped in the ER leads to both an increase in the ubiquitin-proteasome system (UPS) and the ER stress. The presence of ER stress triggers the unfolded protein response (UPR) and/or endoplasmic reticulum-associated degradation (ERAD). The prolonged activation of UPR and ERAD subsequently leads to increased apoptosis. The presence of misfolded GCase in the lysosomes together with a reduction in wild-type GCase levels lead to a retardation of alpha-synuclein degradation via chaperone-mediated autophagy (CMA), which subsequently results in alpha-synuclein accumulation and aggregation. Impaired lysosomal functioning also causes a decrease in the clearance of autophagosomes, and so their accumulation. GBA1 mutations perturb normal mitochondria functioning by increasing generation of free radical species (ROS) and decreasing adenosine triphosphate (ATP) production, oxygen consumption, and membrane potential. GBA1 mutations also lead to accumulation of dysfunctional and fragmented mitochondria. This article is part of a special issue on Parkinson disease. PMID- 26860876 TI - Domestic violence and mental health: a cross-sectional survey of women seeking help from domestic violence support services. AB - BACKGROUND: Domestic violence and abuse (DVA) are associated with increased risk of mental illness, but we know little about the mental health of female DVA survivors seeking support from domestic violence services. OBJECTIVE: Our goal was to characterise the demography and mental health of women who access specialist DVA services in the United Kingdom and to investigate associations between severity of abuse and measures of mental health and health state utility, accounting for important confounders and moderators. DESIGN: Baseline data on 260 women enrolled in a randomized controlled trial of a psychological intervention for DVA survivors were analysed. We report the prevalence of and associations between mental health status and severity of abuse at the time of recruitment. We used logistic and normal regression models for binary and continuous outcomes, respectively. The following mental health measures were used: Clinical Outcomes in Routine Evaluation - Outcome Measure (CORE-OM), Patient Health Questionnaire, Generalised Anxiety Disorder Assessment, and the Posttraumatic Diagnostic Scale to measure posttraumatic stress disorder (PTSD). The Composite Abuse Scale (CAS) measured abuse. RESULTS: Exposure to DVA was high, with a mean CAS score of 56 (SD 34). The mean CORE-OM score was 18 (SD 8) with 76% above the clinical threshold (95% confidence interval: 70-81%). Depression and anxiety levels were high, with means close to clinical thresholds, and more than three-quarters of respondents recorded PTSD scores above the clinical threshold. Symptoms of mental illness increased stepwise with increasing severity of DVA. CONCLUSIONS: Women DVA survivors who seek support from DVA services have recently experienced high levels of abuse, depression, anxiety, and especially PTSD. Clinicians need to be aware that patients presenting with mental health conditions or symptoms of depression or anxiety may be experiencing or have experienced DVA. The high psychological morbidity in this population means that trauma-informed psychological support is needed for survivors who seek support from DVA services. PMID- 26860878 TI - A Description of the Clinical Proteomic Tumor Analysis Consortium (CPTAC) Common Data Analysis Pipeline. AB - The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has produced large proteomics data sets from the mass spectrometric interrogation of tumor samples previously analyzed by The Cancer Genome Atlas (TCGA) program. The availability of the genomic and proteomic data is enabling proteogenomic study for both reference (i.e., contained in major sequence databases) and nonreference markers of cancer. The CPTAC laboratories have focused on colon, breast, and ovarian tissues in the first round of analyses; spectra from these data sets were produced from 2D liquid chromatography-tandem mass spectrometry analyses and represent deep coverage. To reduce the variability introduced by disparate data analysis platforms (e.g., software packages, versions, parameters, sequence databases, etc.), the CPTAC Common Data Analysis Platform (CDAP) was created. The CDAP produces both peptide-spectrum-match (PSM) reports and gene-level reports. The pipeline processes raw mass spectrometry data according to the following: (1) peak-picking and quantitative data extraction, (2) database searching, (3) gene based protein parsimony, and (4) false-discovery rate-based filtering. The pipeline also produces localization scores for the phosphopeptide enrichment studies using the PhosphoRS program. Quantitative information for each of the data sets is specific to the sample processing, with PSM and protein reports containing the spectrum-level or gene-level ("rolled-up") precursor peak areas and spectral counts for label-free or reporter ion log-ratios for 4plex iTRAQ. The reports are available in simple tab-delimited formats and, for the PSM reports, in mzIdentML. The goal of the CDAP is to provide standard, uniform reports for all of the CPTAC data to enable comparisons between different samples and cancer types as well as across the major omics fields. PMID- 26860881 TI - [Bertolotti syndrome: Chronic back pain with mechanical properties due to transverse mega-apophysis]. PMID- 26860879 TI - Effectiveness of a Brief Psychosocial Intervention on Quality of Life of Primary Caregivers of Iranian Children With Cancer: A Randomized Controlled Trial. AB - Cancer in children has a great impact on primary caregiver quality of life (QOL). OBJECTIVE: This study examined the effectiveness of a brief psychosocial intervention (BPI) on QOL of Primary Caregivers of Children with Cancer (PCCCs). METHODS: Sixty-five PCCCs participated in a randomized controlled trial in Mahak Hospital and Rehabilitation Complex in Tehran, Iran. A 5-week long BPI (which comprised of counseling sessions and telephone follow-up) was delivered to the intervention group in addition to usual service, while the control group was provided with usual service. Data were collected using the Caregiver Quality of Life Index-Cancer-Persian version (CQOLC-P) prior to intervention, post intervention, and at follow-up (i.e. 30days after the intervention). Repeated measures analysis of variance analysis (ANOVA) was used to evaluate outcomes. RESULTS: Majority of the participants were mothers (95%), between ages of 24-47 years (95%) with children between ages of 2-12 years. Most child cancer diagnoses were for brain tumors (n=31) and blood cancers (n=17). Significant improvement was found within the intervention group on QOL (p<0.001) including improvements on subscale measures of mental/emotional burden (p<0.001), disruption (p<0.001), and positive adaptation (p<0.001), compared with the control group over time. There was no difference between the intervention and control groups on the financial subscale measure after intervention (p>0.05). CONCLUSION: BPI was an effective strategy to improve the quality of life of PCCCs. Similar interventions can be planned by practitioners to reduce the burden of childhood cancer on PCCCs. PMID- 26860880 TI - [Effect of financial incentives on LDL-cholesterol levels]. PMID- 26860882 TI - [Aminopenicillin-induced exanthematous eruption in a patient with infectious mononucleosis]. PMID- 26860884 TI - Association between the Cardio-Ankle Vascular Index and Executive Function in Community-Dwelling Elderly People. AB - AIM: The aim of this study was to investigate the cross-sectional association between arterial stiffness (AS) measured with the cardio-ankle vascular index (CAVI) and executive function in community-dwelling elderly people. METHODS: Subjects were 140 community-dwelling elderly people who participated in the study at Kobe, Japan during the period of August-September 2014, of which 126 (mean age+/-SD: 73.2+/-6.1, female: 67.5%) met the inclusion criteria and completed the study. Age, sex, body mass index, global cognition, existence of chronic disease, medication, smoking history, and years of education were assessed. The degree of AS was assessed using CAVI. Executive function was assessed using the Category Word Fluency Test (CWFT), Letter Word Fluency Test (LWFT), and Digit Symbol Substitution Test (DSST). We used a correlation analysis and multiple linear regression analysis to investigate whether higher CAVI was independently associated with lower executive function. RESULTS: In the univariate analysis, higher mean CAVI correlated with lower CWFT (rho=-0.21, p=0.020), LWFT (rho= 0.32, p<0.001), and DSST (rho=-0.31, p<0.001). In the multivariate analysis, higher mean CAVI was associated with lower LWFT (beta=-0.21, p=0.046) after adjusting for confounding factors, although there was no association with CWFT (beta=-0.05, p=0.61) and DSST (beta=-0.06, p=0.51). CONCLUSIONS: We found that high CAVI was associated with lower LWFT. These results suggest that arterial stiffness is associated with lower performance in phonemic fluency. PMID- 26860883 TI - Unilateral uveitis masquerade syndrome caused by diffuse large B-cell lymphoma diagnosed using multiparametric flow cytometry of the aqueous humor. AB - BACKGROUND: The uveitis masquerade syndromes (UMS) are a group of ocular diseases that may mimic chronic intraocular inflammation. Many malignant entities such as non-Hodgkin's lymphomas may masquerade as uveitis. We report a case of an HIV positive patient with masquerade syndrome presenting unilateral uveitis. CASE REPORT: 45-year-old Caucasian man with a diagnosis of diffuse large B-cell lymphoma (DLBCL). The patient was diagnosed by a biopsy of an abdominal mass which showed fragments of gastric mucosa with diffuse growth of neoplastic cells. At diagnosis, the patient suffered from unilateral blurring of vision and a sudden decrease of left-eye visual acuity. A slit-lamp examination of the left eye revealed a diagnosis of anterior uveitis. The patient exhibited no signs of posterior uveitis. An anterior-chamber paracentesis was performed and analyzed by multiparameter flow cytometry (MFC), showing cells CD45, CD19, CD20, CD22, and CD38 positives, and moderate expression of CD10 with kappa light chain restriction, showing a monoclonal B-cell population. The patient received CHOP-R with intrathecal methotrexate followed by consolidation high dose methotrexate obtaining a complete response which is ongoing. CONCLUSION: Differential diagnosis between chronic uveitis and ocular lymphoma may be challenging. We advocate anterior-chamber paracentesis in cases of refractory uveitis in patients with hematologic malignancies. (c) 2016 International Clinical Cytometry Society. PMID- 26860885 TI - Crucial Role of the Aryl Hydrocarbon Receptor (AhR) in Indoxyl Sulfate-Induced Vascular Inflammation. AB - AIM: The aryl hydrocarbon receptor (AhR), a ligand-inducible transcription factor mediating toxic effects of dioxins and uremic toxins, has recently emerged as a pathophysiological regulator of immune-inflammatory conditions. Indoxyl sulfate, a uremic toxin, is associated with cardiovascular disease in patients with chronic kidney disease and has been shown to be a ligand for AhR. The aim of this study was to investigate the potential role of AhR in indoxyl sulfate-induced leukocyte-endothelial interactions. METHODS: Endothelial cell-specific AhR knockout (eAhR KO) mice were produced by crossing AhR floxed mice with Tie2 Cre mice. Indoxyl sulfate was administered for 2 weeks, followed by injection of TNF alpha. Leukocyte recruitment to the femoral artery was assessed by intravital microscopy. Vascular endothelial cells were transfected with siRNA specific to AhR (siAhR) and treated with indoxyl sulfate, followed by stimulation with TNF alpha. RESULTS: Indoxyl sulfate dramatically enhanced TNF-alpha-induced leukocyte recruitment to the vascular wall in control animals but not in eAhR KO mice. In endothelial cells, siAhR significantly reduced indoxyl sulfate-enhanced leukocyte adhesion as well as E-selectin expression, whereas the activation of JNK and nuclear factor-kappaB was not affected. A luciferase assay revealed that the region between -153 and -146 bps in the E-selectin promoter was responsible for indoxyl sulfate activity via AhR. Mutational analysis of this region revealed that activator protein-1 (AP-1) is responsible for indoxyl sulfate-triggered E selectin expression via AhR. CONCLUSION: AhR mediates indoxyl sulfate-enhanced leukocyte-endothelial interactions through AP-1 transcriptional activity, which may constitute a new mechanism of vascular inflammation in patients with renal disease. PMID- 26860886 TI - What is the Most Useful Anthropometric Index for Predicting Cardiovascular Disease Risk Factors in Children? PMID- 26860888 TI - Simulating high frequency water quality monitoring data using a catchment runoff attenuation flux tool (CRAFT). AB - High resolution water quality data has recently become widely available from numerous catchment based monitoring schemes. However, the models that can reproduce time series of concentrations or fluxes have not kept pace with the advances in monitoring data. Model performance at predicting phosphorus (P) and sediment concentrations has frequently been poor with models not fit for purpose except for predicting annual losses. Here, the data from the Eden Demonstration Test Catchments (DTC) project have been used to calibrate the Catchment Runoff Attenuation Flux Tool (CRAFT), a new, parsimonious model developed with the aim of modelling both the generation and attenuation of nutrients and sediments in small to medium sized catchments. The CRAFT has the ability to run on an hourly timestep and can calculate the mass of sediments and nutrients transported by three flow pathways representing rapid surface runoff, fast subsurface drainage and slow groundwater flow (baseflow). The attenuation feature of the model is introduced here; this enables surface runoff and contaminants transported via this pathway to be delayed in reaching the catchment outlet. It was used to investigate some hypotheses of nutrient and sediment transport in the Newby Beck Catchment (NBC) Model performance was assessed using a suite of metrics including visual best fit and the Nash-Sutcliffe efficiency. It was found that this approach for water quality models may be the best assessment method as opposed to using a single metric. Furthermore, it was found that, when the aim of the simulations was to reproduce the time series of total P (TP) or total reactive P (TRP) to get the best visual fit, that attenuation was required. The model will be used in the future to explore the impacts on water quality of different mitigation options in the catchment; these will include attenuation of surface runoff. PMID- 26860887 TI - MiR218 Modulates Wnt Signaling in Mouse Cardiac Stem Cells by Promoting Proliferation and Inhibiting Differentiation through a Positive Feedback Loop. AB - MiRNA expression was determined in both proliferating and differentiated cardiac stem cells (CSCs) through a comprehensive miRNA microarray analysis. We selected miR218 for functional follow-up studies to examine its significance in CSCs. First, we observed that the expression of miR218 was altered in CSCs during differentiation into cardiomyocytes, and transfection of an miR218 mimic or miR218 inhibitor affected the myocardial differentiation of CSCs. Furthermore, we observed that a negative regulator of Wnt signaling, sFRP2, was a direct target of miR218, and the protein levels of sFRP2 were increased in cells transfected with the synthetic miR218 inhibitor. In contrast, transfection with the miR218 mimic decreased the expression of sFRP2 and potentiated Wnt signaling. The subsequent down-regulation of sFRP2 by shRNA potentiated Wnt signaling, contributing to a gene expression program that is important for CSC proliferation and cardiac differentiation. Specifically, canonical Wnt signaling induced miR218 transcription. Thus, miR218 and Wnt signaling were coupled through a feed-forward positive feedback loop, forming a biological regulatory circuit. Together, these results provide the first evidence that miR218 plays an important role in CSC proliferation and differentiation through the canonical Wnt signaling pathway. PMID- 26860889 TI - Novel nanowire-structured polypyrrole-cobalt composite as efficient catalyst for oxygen reduction reaction. AB - A novel nanowire-structured polypyrrole-cobalt composite, PPy-CTAB-Co, is successfully synthesized with a surfactant of cetyltrimethylammounium bromide (CTAB). As an electro-catalyst towards oxygen reduction reaction (ORR) in alkaline media, this PPy-CTAB-Co demonstrates a superior ORR performance when compared to that of granular PPy-Co catalyst and also a much better durability than the commercial 20 wt% Pt/C catalyst. Physiochemical characterization indicates that the enhanced ORR performance of the nanowire PPy-CTAB-Co can be attributed to the high quantity of Co-pyridinic-N groups as ORR active sites and its large specific surface area which allows to expose more active sites for facilitating oxygen reduction reaction. It is expected this PPy-CTAB-Co would be a good candidate for alkaline fuel cell cathode catalyst. PMID- 26860890 TI - The Moderating Effect of Job Satisfaction on Physicians' Motivation to Adhere to Financially Incentivized Clinical Practice Guidelines. AB - We examined moderating effects of professional satisfaction on physicians' motivation to adhere to diabetes guidelines associated with pay-for-performance incentives. We merged cross-sectional survey data on attitudes, from 156 primary physicians, with prospective medical record-sourced data on guideline adherence and census data on ambulatory-care population characteristics. We examined moderating effects by testing theory-driven models for satisfied versus discontented physicians, using partial least squares structural equation modeling. Results show that attitudes motivated, while norms suppressed, adherence to guidelines among discontented physicians. Separate models for satisfied versus discontented physicians revealed motivational differences. Satisfied physicians disregarded intrinsic and extrinsic influences and biases. Discontented physicians, alienated by social pressure, favored personal inclinations. To improve adherence to guidelines among discontented physicians, incentives should align with personal attitudes and incorporate promotional campaigns countering resentment of peer and organizational pressure. PMID- 26860892 TI - Ponatinib attenuates experimental pulmonary arterial hypertension by modulating Wnt signaling and vasohibin-2/vasohibin-1. AB - AIMS: An abnormal ratio of vasohibin-2/vasohibin-1 may be involved in the abnormal angiogenesis and vascular remodeling during pulmonary arterial hypertension (PAH). MAIN METHODS: To evaluate the pharmacological actions of Ponatinib (AP) in experimental model of PAH, the effects of AP on TGF-beta1 mediated endothelial-mesenchymal transition (EndoMT) in human pulmonary microvascular endothelial cells (HPMEC), and the hypoxic human pulmonary artery smooth muscle cells (HPASMC) proliferation and HPMEC in vitro, and on bleomycin (BLM)-induced PAH in vivo were investigated. KEY FINDINGS: AP treatment resulted in a reduction of EndoMT in HPMECs with a decrease of vimentin, whereas an increase of VE-cadherin, reduction of fibroblast growth factor (FGF-2), vascular endothelial growth factor (VEGF) and vasohibin-2 (VASH-2), whereas an increase of vasohibin-1 (VASH-1) in the hypoxic HPMEC, a reduction of the HPASMC proliferation with decreases of wnt5a, beta-catenin and cyclin D1 expression. AP ameliorated BLM-induced PAH in rats with reductions of FGF-2, VEGF, von Willebrand factor (vWF) and VASH-2 expression, whereas an increase of VASH-1 expression. AP ameliorated BLM-induced PAH in rats with reductions of the pathological score and the collagen deposition. In addition, AP ameliorated hemodynamics and right ventricular hypertrophy. SIGNIFICANCES: Our results identified a therapeutic potential of AP in PAH therapy might be modulated VASH 2/VASH-1 and the Wnt signaling. PMID- 26860891 TI - KatG and KatE confer Acinetobacter resistance to hydrogen peroxide but sensitize bacteria to killing by phagocytic respiratory burst. AB - AIMS: Catalase catalyzes the degradation of H2O2. Acinetobacter species have four predicted catalase genes, katA, katE, katG, and katX. The aims of the present study seek to determine which catalase(s) plays a predominant role in determining the resistance to H2O2, and to assess the role of catalase in Acinetobacter virulence. MAIN METHODS: Mutants of Acinetobacter baumannii and Acinetobacter nosocomialis with deficiencies in katA, katE, katG, and katX were tested for sensitivity to H2O2, either by halo assays or by liquid culture assays. Respiratory burst of neutrophils, in response to A. nosocomialis, was assessed by chemiluminescence to examine the effects of catalase on the production of reactive oxygen species (ROS) in neutrophils. Bacterial virulence was assessed using a Galleria mellonella larva infection model. KEY FINDINGS: The capacities of A. baumannii and A. nosocomialis to degrade H2O2 are largely dependent on katE. The resistance of both A. baumannii and A. nosocomialis to H2O2 is primarily determined by the katG gene, although katE also plays a minor role in H2O2 resistance. Bacteria lacking both the katG and katE genes exhibit the highest sensitivity to H2O2. While A. nosocomialis bacteria with katE and/or katG were able to decrease ROS production by neutrophils, these cells also induced a more robust respiratory burst in neutrophils than did cells deficient in both katE and katG. We also found that A. nosocomialis deficient in both katE and katG was more virulent than the wildtype A. nosocomialis strain. SIGNIFICANCE: Our findings suggest that inhibition of Acinetobacter catalase may help to overcome the resistance of Acinetobacter species to microbicidal H2O2 and facilitate bacterial disinfection. PMID- 26860893 TI - Anaerobic threshold employed on exercise training prescription and performance assessment for laboratory rodents: A short review. AB - Several studies have generated numerous terms in the field of exercise training prescription and performance assessment that often do not match the information previously demonstrated by many other works, generating much debate and resulting in an immense pool of scientific results. Several protocols in exercise training prescription and performance assessment have been proposed for these purposes by many reasons. In the field of exercise science, the protocol must be thoroughly investigated and provide real tools to be reproducible. Many laboratories have been adapting and developing evaluation protocols and testing on physical training of rodents in different experimental conditions. In this context, mice, rats and rabbits are preferentially chosen due to easy manipulation and good response to exercise, and comparable at results obtained with humans in compatible effort intensities. But, the exercise training programs and aerobic anaerobic transition assessment proposed for animal models vary extensively, depending on the species, gender, age, type of stimulus, type of exercise, type of method and also on the specific objectives of the program. This short review demonstrates the need in offering tools performed by invasive measurement to assess the anaerobic threshold by blood lactate employed on evolution of aerobic anaerobic parameters of rodents. The objective of this short review was to present and to discuss physical evaluation protocols applications to rodents. The table submitted may give a basis for anaerobic threshold employed on exercise training prescription and performance assessment for laboratory rodents in future research. PMID- 26860894 TI - Nanometer resolution optical coherence tomography using broad bandwidth XUV and soft x-ray radiation. AB - Optical coherence tomography (OCT) is a non-invasive technique for cross sectional imaging. It is particularly advantageous for applications where conventional microscopy is not able to image deeper layers of samples in a reasonable time, e.g. in fast moving, deeper lying structures. However, at infrared and optical wavelengths, which are commonly used, the axial resolution of OCT is limited to about 1 MUm, even if the bandwidth of the light covers a wide spectral range. Here, we present extreme ultraviolet coherence tomography (XCT) and thus introduce a new technique for non-invasive cross-sectional imaging of nanometer structures. XCT exploits the nanometerscale coherence lengths corresponding to the spectral transmission windows of, e.g., silicon samples. The axial resolution of coherence tomography is thus improved from micrometers to a few nanometers. Tomographic imaging with an axial resolution better than 18 nm is demonstrated for layer-type nanostructures buried in a silicon substrate. Using wavelengths in the water transmission window, nanometer-scale layers of platinum are retrieved with a resolution better than 8 nm. XCT as a nondestructive method for sub-surface tomographic imaging holds promise for several applications in semiconductor metrology and imaging in the water window. PMID- 26860896 TI - Add-on unidirectional elastic metamaterial plate cloak. AB - Metamaterial cloaks control the propagation of waves to make an object invisible or insensible. To manipulate elastic waves in space, a metamaterial cloak is typically embedded in a base system that includes or surrounds a target object. The embedding is undesirable because it structurally weakens or permanently alters the base system. In this study, we propose a new add-on metamaterial elastic cloak that can be placed over and mechanically coupled with a base structure without embedding. We designed an add-on type annular metamaterial plate cloak through conformal mapping, fabricated it and performed cloaking experiments in a thin-plate with a hole. Experiments were performed in a thin plate by using the lowest symmetric Lamb wave centered at 100 kHz. As a means to check the cloaking performance of the add-on elastic plate cloak, possibly as a temporary stress reliever or a so-called "stress bandage", the degree of stress concentration mitigation and the recovery from the perturbed wave field due to a hole were investigated. PMID- 26860895 TI - Regulating ehrlich and demethiolation pathways for alcohols production by the expression of ubiquitin-protein ligase gene HUWE1. AB - Ehrlich and demethiolation pathways as two competing branches converted amino acid into alcohols. Controlling both pathways offers considerable potential for industrial applications including alcohols overproduction, flavor-quality control and developing new flavors. While how to regulate ehrlich and demethiolation pathways is still not applicable. Taking the conversion of methionine into methionol and methanethiol for example, we constructed two suppression subtractive cDNA libraries of Clonostachys rosea by using suppression subtractive hybridization (SSH) technology for screening regulators controlling the conversion. E3 ubiquitin-protein ligase gene HUWE1 screened from forward SSH library was validated to be related with the biosynthesis of end products. Overexpressing HUWE1 in C. rosea and S. cerevisiae significantly increased the biosynthesis of methanethiol and its derivatives in demethiolation pathway, while suppressed the biosynthesis of methional and methionol in ehrlich pathway. These results attained the directional regulation of both pathways by overexpressing HUWE1. Thus, HUWE1 has potential to be a key target for controlling and enhancing alcohols production by metabolic engineering. PMID- 26860897 TI - Clinicopathological features of primary gastric neuroendocrine neoplasms: A single-center analysis. AB - OBJECTIVE: To assess the clinical characteristics, diagnosis and therapeutic modalities for gastric neuroendocrine neoplasms (GNENs) among the Chinese population in a single institution. METHODS: A total of 57 patients with histologically confirmed GNENs, who were diagnosed between 1995 and 2015 at the Peking Union Medical College Hospital were retrospectively reviewed. The clinical, imaging and histopathologic characteristics as well as the treatments of GNENs were collected and analyzed. RESULTS: Patients with GNENs mostly presented with non-specific symptoms. Gastric body was the most common site of involvement. The choice of imaging modality, such as endoscopy and computed tomography depended on the tumor subtype. Chromogranin A (CgA) and synaptophysin were indispensable immunohistochemical markers for diagnosis. Significant inter group differences in the positivity rate of CD56 were observed among the three grades (G1, G2 and G3). Therapeutic modalities included endoscopic intervention, surgical resection and pharmacotherapy, which were largely guided by the tumor subtype and the presence or absence of distant metastasis or tumor recurrence. CONCLUSIONS: Routine endoscopic examination is recommended for the early diagnosis of GNENs. Histopathological examination can make the definite diagnosis of GNENs and clarify the nature of gastric polyps. A multidisciplinary approach is important in the management of patients with GNENs. PMID- 26860898 TI - Modification of hemi-Fontan operation for patients with functional single ventricle and anomalous pulmonary venous connection to the superior vena cava: mid-term results. AB - OBJECTIVES: Fontan candidates with mixed totally anomalous pulmonary venous connection often have postoperative pulmonary venous obstruction after cavopulmonary anastomosis. Because some pulmonary venous obstructions have no intimal hypertrophy at reoperation, we considered such pulmonary venous obstructions to be caused by 3D deformities arising from dissection or mobilization of the vessels, and hypothesized that keeping the pulmonary venous branches in a natural position could avoid such obstruction. Here, we evaluated a modified hemi-Fontan strategy consisting of minimal dissection with no division of vessels and patch separation between systemic and pulmonary venous flow. METHODS: We retrospectively reviewed clinical records of infants with a functional single ventricle and supracardiac anomalous pulmonary venous connection who had undergone this procedure between 2002 and 2012. RESULTS: Nine infants underwent this procedure (median age, 5.6 months; range 3.2-30), all with right atrial isomerism and several pulmonary venous branches directly and separately connecting to the superior vena cava. In 5 patients, all pulmonary veins drained into the superior vena cava; in 1, the right pulmonary veins drained into the superior vena cava and in 3, a pulmonary venous branch drained into the superior vena cava. The median follow-up was 6.9 years (0.8-13 years). Three patients underwent reoperation for postoperative pulmonary venous obstruction caused by intimal hypertrophy; however, we confirmed no pulmonary venous obstruction caused by 3D deformities on the pulmonary venous branches connecting separately to the superior vena cava. Although 2 patients were effectively relieved from pulmonary venous obstruction, 1 died due to recurrent pulmonary venous obstruction. There was no late death and no sinus-node dysfunction. Eight patients underwent successful Fontan operation and catheterization. The median interval from the Fontan operation to the latest catheterization was 3.7 years (0.9-3.7 years). The median arterial oxygen saturation was 94% (91-97%) and the central venous pressure was 12 mmHg (8-14 mmHg); no deficiency of pulmonary arteries and veins was noted. CONCLUSIONS: For patients with functional single ventricle and anomalous pulmonary venous connections to the superior vena cava, our novel strategy of second-stage palliation could avoid postoperative pulmonary venous obstruction caused by 3D deformities, but may not eliminate pulmonary venous obstruction caused by intimal hypertrophy. PMID- 26860900 TI - Trajectories of need: understanding patients' use of support during the journey through knee replacement. AB - PURPOSE: To explore how the process of undergoing and recovering from knee replacement surgery alters patients' experiences and use of their support networks. METHODS: Ten patients having knee replacement surgery for osteoarthritis were invited to take part in in-depth interviews prior to surgery and 2-4 weeks, 6 and 12 months post-operatively. Transcripts were analyzed using Interpretative Phenomenological Analysis. RESULTS: Three superordinate themes were identified: (1) relationships with health professionals over the knee replacement journey; (2) implications for informal relationships and support networks and (3) providing support to others. CONCLUSIONS: Transformation from a person with osteoarthritis to someone recovering from a surgical intervention can lead to alterations in the source, type and level of support people receive from others, and can also change the assistance that they themselves are able to offer. Findings highlight the value of the concept of interdependence to our understanding of participants' experiences. Activity undertaken by informal support networks assists participants to cope with the consequences of osteoarthritis and surgery, and fills in the gap when more formal support is lacking. However, it is essential that provision of care is individually tailored and that formal support is adequate at times when informal support networks are unavailable. Implications for Rehabilitation Activity undertaken by informal support networks can help patients who undergo knee replacement cope with the consequences of their operation; filling the void when support from health professionals is lacking. Contact with health professionals after surgery enhances confidence and offers reassurance; helping to facilitate the recovery process from knee replacement. Findings highlight, from patients' own perspectives, the potential value of post-operative physiotherapy received soon after surgery and the possible role of long-term follow up. Missing or ill-timed support from health professionals can have negative psychosocial consequences for patients going through joint replacement. PMID- 26860899 TI - Cardiac function in adults following minimally invasive repair of pectus excavatum. AB - OBJECTIVES: To study if minimally invasive repair of pectus excavatum (PE) in adult patients would improve cardiopulmonary function at rest and during exercise as we have found previously in young and adolescent patients with PE. METHODS: Nineteen adult patients (>21 year of age) were studied at rest and during bicycle exercise before surgery and 1 year postoperatively. Lung spirometry was performed at rest. Cardiac output, heart rate and aerobic exercise capacity were measured using a photo-acoustic gas-rebreathing technique during rest and exercise. Data are shown as mean +/- standard deviation. RESULTS: Fifteen patients completed the 1-year follow-up. No significant differences were found in neither cardiac output (14.0 +/- 0.9 l min at baseline vs 14.8 +/- 1.1 l min after surgery; P = 0.2029), nor maximum oxygen uptake (30.4 +/- 1.9 and 33.3 +/- 1.6 ml/kg/min; P = 0.0940 postoperatively). The lung spirometry was also unchanged, with no difference in forced expiratory capacity during the first second. CONCLUSIONS: Correction of PE in adult patients does not improve the cardiopulmonary function 1 year after surgery as seen in children and adolescents. PMID- 26860901 TI - Long-term physical activity modulates brain processing of somatosensory stimuli: Evidence from young male twins. AB - Leisure-time physical activity is a key contributor to physical and mental health. Yet the role of physical activity in modulating cortical function is poorly known. We investigated whether precognitive sensory brain functions are associated with the level of physical activity. Physical activity history (3-yr LTMET), physiological measures and somatosensory mismatch response (sMMR) in EEG were recorded in 32 young healthy twins. In all participants, 3-yr-LTMET correlated negatively with body fat%, r=-0.77 and positively with VO2max, r=0.82. The fat% and VO2max differed between 15 physically active and 17 inactive participants. Trend toward larger sMMR was seen in inactive compared to active participants. This finding was significant in a pairwise comparison of 9 monozygotic twin pairs discordant for physical activity. Larger sMMR reflecting stronger synchronous neural activity may reveal diminished gating of precognitive somatosensory information in physically inactive healthy young men compared to the active ones possibly rendering them more vulnerable to somatosensory distractions from their surroundings. PMID- 26860902 TI - Need for increased investment in public health. PMID- 26860903 TI - Mortality Risk for Acute Cholangitis (MAC): a risk prediction model for in hospital mortality in patients with acute cholangitis. AB - BACKGROUND: Acute cholangitis is a life-threatening bacterial infection of the biliary tract. Main focus of this study was to create a useful risk prediction model that helps physicians to assign patients with acute cholangitis into different management groups. METHODS: 981 cholangitis episodes from 810 patients were analysed retrospectively at a German tertiary center. RESULTS: Out of eleven investigated statistical models fit to 22 predictors, the Random Forest model achieved the best (cross-)validated performance to predict mortality. The receiver operating characteristics (ROC) curve revealed a mean area under the curve (AUC) of 91.5 %. Dependent on the calculated mortality risk, we propose to stratify patients with acute cholangitis into a high and low risk group. The mean sensitivity, specificity, positive and negative predictive value of the corresponding optimal cutpoint were 82.9 %, 85.1 %, 19.0 % and 99.3 %, respectively. All of these results emerge from nested (cross-)validation and are supposed to reflect the model's performance expected for external data. An implementation of our risk prediction model including the specific treatment recommendations adopted from the Tokyo guidelines is available on http://www2.imse.med.tum.de:3838/ . CONCLUSION: Our risk prediction model for mortality appears promising to stratify patients with acute cholangitis into different management groups. Additional validation of its performance should be provided by further prospective trails. PMID- 26860904 TI - Measurement of betamethasone concentration in maternal serum treated for fetal lung maturity; Is it feasible? AB - BACKGROUND: The association between maternal serum concentration of betamethasone given for fetal lung maturity and perinatal outcome has not been investigated. This may be due to an absence of a reliable method for measuring serum betamethasone concentrations. We aimed in the current study to assess the feasibility of a specific ELISA kit to measure the concentrations of betamethasone in maternal serum and to examine the trend of sequential measurements after a course of betamethasone for fetal lung maturity. METHODS: Pregnant women at risk for preterm birth who received betamethasone between 24 and 34 weeks of gestation were prospectively included. Serum concentrations were determined before administering betamethasone (baseline), and 36 hours, 48 hours, 72 hours, and 5 to 7 days after the 1(st) dose. Betamethasone concentration in samples was determined using Corticosteroid ELISA kit. The Friedman test was used to test whether there were significant differences between the measurements. RESULTS: Five singleton pregnancies were included. Using the ELISA kit, betamethasone concentration in maternal serum samples was obtained for all women. Among the five measurements performed, the concentration was highest at 36 hours after the 1(st) dose and close to baseline at the 5(th) measurement performed after 5 to 7 days (p < 0.05). Serum concentration varied at each time point between the five women but similar trend was observed. CONCLUSION: Betamethasone concentration is measurable in the serum of pregnant women with this ELISA kit. PMID- 26860905 TI - Squamous Dysplasia of the Urinary Bladder: A Consecutive Cystectomy Series. AB - Squamous dysplasia of the urinary bladder is uncommon and may represent a precursor to invasive squamous cell carcinoma. Though significant focus has been devoted to squamous differentiation in invasive bladder cancer, relatively little attention has been given to squamous dysplasia. We methodically reviewed microscopic slides from a consecutive cystectomy series at our institution (n = 303; 2001-2014), with special attention given to squamous dysplasia and squamous differentiation within association invasive carcinoma. Of these 303 cases, 3% (9 cases) had squamous dysplasia. The majority (89%; 8/9) had a similar morphological appearance to squamous dysplasia of the head and neck (ie, cytological atypia, architectural disturbances, and abnormal keratinization). Invasive carcinoma was present in 230 of the cystectomy cases. Of these 230 cases with invasive carcinoma, 4% (8 cases) also had squamous dysplasia. The invasive carcinoma had evidence of squamous differentiation in all cases with concurrent squamous dysplasia. Concurrent flat urothelial carcinoma in situ was present in 3 of the 8 cases with both invasive carcinoma and squamous dysplasia. Squamous dysplasia was not associated with clinical outcomes data, including death from bladder cancer and bladder cancer recurrence. The data from this study indicate that squamous dysplasia is uncommon in the cystectomy setting, frequently has the morphology of head and neck dysplasia, and is often associated with invasive carcinoma with squamous differentiation. PMID- 26860906 TI - Guidelines or guidance for better idiopathic pulmonary fibrosis management? AB - Idiopathic pulmonary fibrosis (IPF) is a rare fibrotic interstitial lung disease with a relentlessly progressive course and fatal outcome. Guidelines summarizing the current evidence and providing evidence-based recommendations for the treatment of rare diseases such as IPF are important since individual physicians often have limited experience. Nevertheless, the available evidence is often scarce and, therefore, evidence-based recommendations are prone to being vague or with low confidence, thus creating uncertainty instead of guidance. Moreover, the effect of guidelines themselves on clinical practice has not been sufficiently evaluated. On the other hand, expert opinion may be biased and lead to the misinterpretation of evidence, resulting in misleading recommendations and a potential harm to patients. This editorial focuses on the advantages and disadvantages of evidence-based guidelines and professional experience in the context of a rare disease such as IPF and tries to assess the optimum combination of both approaches.Please see related commentary articles: http://dx.doi.org/10.1186/s12916-016-0562-1 and http://dx.doi.org/10.1186/s12916 016-0563-0. PMID- 26860907 TI - Knowledge, attitude and practices: assessing maternal and child health care handbook intervention in Vietnam. AB - BACKGROUND: Maternal and Child Health (MCH) Handbook, an integrated MCH home based record, was piloted in four provinces of Vietnam (Dien Bien, Hoa Binh, Thanh Hoa and An Giang). The study is aimed at assessing the changes in pregnant women's behavior towards the frequencies of their antenatal care service utilizations and their subsequent breastfeeding practices up to six months of age, through the MCH Handbook intervention. This is because the levels of pregnant women's knowledge, attitude and practices (KAP) towards their antenatal care service utilizations and exclusive breastfeeding practices have been previously neither analyzed nor reported in relation to MCH home-based records in the country. METHODS: To compare pre-intervention baseline in 2011, post intervention data were collected in 2013. Structured interviews were conducted with randomly selected 810 mothers of children 6-18 months of age in the four provinces. A focus group discussion among mothers in each of four provinces was conducted. RESULTS: There was no significant difference in pregnant women's knowledge about the need for >=3 antenatal care visits between pre- and post interventions. Yet, the proportion of pregnant women who made >=3 antenatal care visits in post-intervention was significantly higher than in pre-intervention. Thus, MCH Handbook is likely to have contributed to practicing >=3 antenatal care visits, by changing their attitude. The proportion of mothers who know the need for exclusive breastfeeding necessary during the initial six months significantly increased between pre- and post-interventions. The proportion of those practicing exclusive breastfeeding significantly increased between pre- and post interventions, too. Thus, MCH Handbook is likely to have contributed to the increase in both knowledge about and practices of exclusive breastfeeding. CONCLUSION: The results of study imply that MCH Handbook contributed to the increase in pregnant women's practices of >=3 antenatal care visits and in their knowledge about and practice of exclusive breastfeeding. While there is room for improvement in the level of its data recording, the study confirmed that MCH Handbook plays a catalytic role in ensuring a continuum of maternal, newborn and child care. Note that this study is the first study that attempted to estimate pregnant women's behavioral changes through MCH Handbook intervention in Vietnam. PMID- 26860909 TI - Altered modular organization of intrinsic brain functional networks in patients with Parkinson's disease. AB - Although previous studies reported altered topology of brain functional networks in patients with Parkinson's disease (PD), the modular organization of brain functional networks in PD patients remains largely unknown. Using the resting state functional MRI (R-fMRI) and graph theory, we examined the modular organization of brain functional networks in 32 unmedicated patients with early to-mid motor stage PD and 31 healthy controls. Compared to the controls, the PD patients tended to show decreased integrity and segregation, both within and between modules. This was inferred by significantly increased intra-modular characteristic path length (L p) within four modules: mPFC, SN, SMN, and FPN, decreased inter-modular functional connectivity (FC) between mPFC and SN, SMN, and VN, and decreased intra-modular clustering in the PD patients. Intra-modular characteristic path length within the mPFC showed significantly positive correlation with general cognitive ability in the PD group. Receiver operating characteristic (ROC) analysis revealed that FC between mPFC and SN had the highest significant accuracy in differentiating the patients from the controls. Our findings may provide new insight in understanding the pathological changes that underlie impairment in cognition and movement in Parkinson's disease. PMID- 26860908 TI - Individual differences in emotion word processing: A diffusion model analysis. AB - The exploratory study investigated individual differences in implicit processing of emotional words in a lexical decision task. A processing advantage for positive words was observed, and differences between happy and fear-related words in response times were predicted by individual differences in specific variables of emotion processing: Whereas more pronounced goal-directed behavior was related to a specific slowdown in processing of fear-related words, the rate of spontaneous eye blinks (indexing brain dopamine levels) was associated with a processing advantage of happy words. Estimating diffusion model parameters revealed that the drift rate (rate of information accumulation) captures unique variance of processing differences between happy and fear-related words, with highest drift rates observed for happy words. Overall emotion recognition ability predicted individual differences in drift rates between happy and fear-related words. The findings emphasize that a significant amount of variance in emotion processing is explained by individual differences in behavioral data. PMID- 26860910 TI - [Surgery at the interface between technique, ethics and economy]. PMID- 26860911 TI - No evidence of persistent parvovirus B19 viremia among Iranian patients with HIV after a 1-year follow-up. AB - Recent studies have demonstrated that, in common with other latent viruses, parvovirus B19 infection can be controlled by the host immune response but may persist in some places such as the bone marrow. Persistent B19 infection has been found in both immunocompetent and immunocompromised individuals, such as patients infected with human immunodeficiency virus (HIV). However, there is limited data regarding long-term B19 viremia in HIV patients. In this study, we investigated virological and hematological findings, and also the clinical outcome, of seven cases of HIV/B19 coinfection (confirmed by PCR) after one year. These cases were provided from a previous study on patients with HIV infection that found B19 DNA in 13 cases. Seven of these 13 patients were available after 1 year, and we retested them for B19 viremia and B19-specific antibodies. B19 IgG was tested by ELISA, and B19 DNA was assessed by nested PCR. Anemia was not observed in these cases. All subjects had cleared viremia, but B19 IgG seroconversion occurred in two cases. No significant changes in CD4 and hemoglobin occurred. The results of this study indicate that B19 infection in HIV patients is a subtle infection and that B19 viremia is not a long-term event. PMID- 26860912 TI - The influence of host factors and sequence variability of the p7 region on the response to pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b in patients from Serbia. AB - The goal of this study was to identify host and viral factors affecting the response to pegylated interferon/ribavirin (PEG-IFN/RBV) treatment in patients with chronic hepatitis C genotype 1b. Baseline characteristics of the patients and sequences within the p7 region were analyzed in pre-treatment serum samples from 53 individuals with chronic hepatitis C genotype 1b and related to the outcome of therapy. We found a significant correlation between age and response to therapy (p < 0.001). Furthermore, the pre-treatment viral load was closely associated with the stage of liver fibrosis (p < 0.001). The presence of fewer than 4 mutations and age above 40 were significantly associated with non-response (NR) (p < 0.001). Our findings may be useful for estimating the likelihood of achieving a sustained virologic response (SVR) in patients who are chronically infected with hepatitis C virus genotype 1b. PMID- 26860913 TI - Analysis of full-length genomes of porcine teschovirus (PTV) and the effect of purifying selection on phylogenetic trees. AB - To study the outcome of natural selection using phylogenetic trees, we analyzed full-length genome sequences of porcine teschovirus (PTV). PTV belongs to the family Picornaviridae and has a positive-stranded RNA genome, the replication of which is carried out by the error-prone viral RNA-dependent RNA polymerase. The viral RNA encodes a single polyprotein that is cleaved into structural (i.e., L, VP4, VP2, VP3 and VP1) and nonstructural proteins (i.e., 2A, 2B, 2C, 3A, 3B, and 3C). A high degree of genetic diversity was found based on the pairwise nucleotide distances and on the mean ratio of the number of nonsynonymous (dN) and synonymous (dS) substitutions (dN/dS) in the structural genes. Conversely, the diversity of the nonstructural genes was lower. The differences in genetic diversity between the structural and nonstructural genomic regions were likely due to strong purifying selection; consequently, the estimates of phylogenies were also discordant among these genes. In particular, maximum-likelihood and Bayesian methods generated short-branched trees when loci that are under strong purifying selection were used. These findings indicate that even in an RNA virus with an intrinsically high mutation rate, a strong purifying selection will curb genetic diversity and should be considered an important source of bias in future studies based on phylogenetic methods. PMID- 26860915 TI - Applications of Paper and Interactive Prototypes in Designing Telecare Services for Older Adults. AB - We present the results of the user studies of the CareMe prototype telecare service for supporting older adults with remote telecare services. The CareMe solution targets older adults who are capable of living independently and outside of a dedicated medical institution or a nursing home, but require occasional medical attention, and formal or informal care. The studies were conducted between November 2013 and March 2014 and followed the participatory design approach. The research questions focused on understanding the difference in the participatory design approach when older adults use paper prototypes vs interactive prototypes, and the difference when older adults use interactive prototypes with poor interface design vs interactive prototypes with rich interface design. In total, 45 older adults living in Slovenia participated in the field trial. They were retired, 32 of whom were nursing home residents and 13 were living independently at home. The study sample's age distribution was between 64 and 91 years. The analysis of the filed trial results indicated the importance of the factors that influence users' decision about how and when they use new technology, i.e., the perceived usefulness and the perceived ease-of-use. Main insights gained from the studies show, that it is very difficult to keep older people focused on the topics of discussion and that they have often difficulties to clearly present/express their ideas. Furthermore, abstract concepts, such as paper only prototypes proved to be challenging to cope with, whereas using real applications and services when trying out scenarios using interactive prototypes provided much better experience and feedback. PMID- 26860914 TI - Effect of Watermarking on Diagnostic Preservation of Atherosclerotic Ultrasound Video in Stroke Telemedicine. AB - Embedding of diagnostic and health care information requires secure encryption and watermarking. This research paper presents a comprehensive study for the behavior of some well established watermarking algorithms in frequency domain for the preservation of stroke-based diagnostic parameters. Two different sets of watermarking algorithms namely: two correlation-based (binary logo hiding) and two singular value decomposition (SVD)-based (gray logo hiding) watermarking algorithms are used for embedding ownership logo. The diagnostic parameters in atherosclerotic plaque ultrasound video are namely: (a) bulb identification and recognition which consists of identifying the bulb edge points in far and near carotid walls; (b) carotid bulb diameter; and (c) carotid lumen thickness all along the carotid artery. The tested data set consists of carotid atherosclerotic movies taken under IRB protocol from University of Indiana Hospital, USA AtheroPointTM (Roseville, CA, USA) joint pilot study. ROC (receiver operating characteristic) analysis was performed on the bulb detection process that showed an accuracy and sensitivity of 100 % each, respectively. The diagnostic preservation (DPsystem) for SVD-based approach was above 99 % with PSNR (Peak signal-to-noise ratio) above 41, ensuring the retention of diagnostic parameter devalorization as an effect of watermarking. Thus, the fully automated proposed system proved to be an efficient method for watermarking the atherosclerotic ultrasound video for stroke application. PMID- 26860916 TI - Special Issue JOMS - Journal of Medical Systems, 2016 on Agent-Empowered HealthCare Systems. PMID- 26860917 TI - An Automatic 3-D Reconstruction of Coronary Arteries by Stereopsis. AB - Stereopsis of X-ray images can produce 3D tree of coronary arteries up to a certain accuracy level with a lower dose of radiation when compared to computer tomography (CT). In this study, a novel and complete automatic system is designed that covers preprocessing, segmentation, matching and reconstruction steps for that purpose. First, an automatic and novel pattern recognition technique is applied for extraction of the bifurcation points with their diameters recorded in a map. Then, a novel optimization algorithm is run for matching the branches efficiently which is based on that map and the epipolar geometry of stereopsis. Finally, cut branches are fixed one by one at the bifurcations for completing the 3D reconstruction. This method prevails the similar ones in the literature with this novelty since it automatically and inherently prevents the wrong overlapping of branches. Other essential problems like correct detection of the bifurcations and accurate calibration parameters and fast overlapping of matched branches are addressed at acceptable levels. The accuracy of bifurcation extraction is high at 90 % with 96 % sensitivity. Accuracy of vessel centerlines has rootmean-square (rms) error smaller than 0.57 mm for 20 different patients. For phantom model, rms error is 0.75 +/- 0.8 mm in 3D localization. PMID- 26860918 TI - The Impact of Overestimations of Surgical Control Times Across Multiple Specialties on Medical Systems. AB - Optimization of operating room (OR) resources and costs require accurate estimations of procedure times. In some institutions, surgeons are asked to predict their surgical control time (SCT), which typically constitutes the majority of the total procedure time. Here, we examine differences in predicted versus actual SCT and variations by specialty. Data included all scheduled surgical procedures at one academic institution from October 2008 - September 2014. Exclusion criteria consisted of missing values for SCT as well as estimated SCTs that fell outside of 5 standard deviations of any given procedure's mean. Differences in estimation were calculated by subtracting estimated SCT from actual SCT and compared against a null hypothesis of 0 with a two-tailed t-test. Differences between specialties were examined using analysis of variance and Games-Howell tests. Between 2008 and 2014, 119,410 scheduled procedures were performed. After exclusion, 116,599 cases were analyzed. On average, SCT was overestimated by 12.9 min (p < 0.0001). Overestimations persisted when divided by specialty (p < 0.0001). With thoracic surgery as a control, all other specialties except for cardiac surgery had overestimations of SCT. The greatest time differences were seen in dental (37.6 min, p < 0.0001), cardiology (33.0 min, p < 0.0001), and neurosurgery (29.7 min, p < 0.0001). Overall, SCTs are overestimated at this institution across many specialties. Depending on the methodology by which a hospital chooses to allocate OR time, SCT estimations could potentially be reduced in certain specialties to allow for better allocation of OR resources. PMID- 26860919 TI - Prevalence and determinants of medication non-adherence in chronic pain patients: a systematic review. AB - BACKGROUND: Chronic pain is commonly treated with analgesic medication. Non adherence to prescribed pain medication is very common and may result in sub optimal treatment outcome. The aim of this review was to investigate the prevalence of medication non-adherence and to present determinants that may help identify patients at risk for non-adherence to analgesic medication. METHODS: A search was performed in PubMed and Embase with systematic approach including PRISMA recommendations. Individual risk of bias was assessed and systematic data extraction was performed. RESULTS: Twenty-five studies were included. Non adherence rates to pain prescriptions ranged from 8% to 62% with a weighted mean of 40%. Underuse of pain medication was more common than overuse in most studies. Factors that were commonly positively associated with non-adherence were dosing frequency, polymedication, pain intensity, and concerns about pain medication. Factors negatively associated with non-adherence were age, again pain intensity and quality of the patient-caregiver relationship. Underuse was positively associated with active coping strategies and self-medication, and negatively associated with perceived need for analgesic medication. Overuse was positively associated with perceived need, pain intensity, opioid use, number of prescribed analgesics, a history of drug abuse, and smoking. CONCLUSION: Non-adherence to analgesic medication use is very common in the chronic pain population. The choice for pharmacological therapy should not only be based upon pain diagnosis but should also take the risks of non-adherence into account. The value of adherence monitoring or adherence enhancing interventions has to be investigated in future studies. PMID- 26860920 TI - A neurorobotic platform for locomotor prosthetic development in rats and mice. AB - OBJECTIVES: We aimed to develop a robotic interface capable of providing finely tuned, multidirectional trunk assistance adjusted in real-time during unconstrained locomotion in rats and mice. APPROACH: We interfaced a large-scale robotic structure actuated in four degrees of freedom to exchangeable attachment modules exhibiting selective compliance along distinct directions. This combination allowed high-precision force and torque control in multiple directions over a large workspace. We next designed a neurorobotic platform wherein real-time kinematics and physiological signals directly adjust robotic actuation and prosthetic actions. We tested the performance of this platform in both rats and mice with spinal cord injury. MAIN RESULTS: Kinematic analyses showed that the robotic interface did not impede locomotor movements of lightweight mice that walked freely along paths with changing directions and height profiles. Personalized trunk assistance instantly enabled coordinated locomotion in mice and rats with severe hindlimb motor deficits. Closed-loop control of robotic actuation based on ongoing movement features enabled real-time control of electromyographic activity in anti-gravity muscles during locomotion. SIGNIFICANCE: This neurorobotic platform will support the study of the mechanisms underlying the therapeutic effects of locomotor prosthetics and rehabilitation using high-resolution genetic tools in rodent models. PMID- 26860921 TI - An Integrative Data Science Pipeline to Identify Novel Drug Interactions that Prolong the QT Interval. AB - INTRODUCTION: Drug-induced prolongation of the QT interval on the electrocardiogram (long QT syndrome, LQTS) can lead to a potentially fatal ventricular arrhythmia known as torsades de pointes (TdP). Over 40 drugs with both cardiac and non-cardiac indications are associated with increased risk of TdP, but drug-drug interactions contributing to LQTS (QT-DDIs) remain poorly characterized. Traditional methods for mining observational healthcare data are poorly equipped to detect QT-DDI signals due to low reporting numbers and lack of direct evidence for LQTS. OBJECTIVE: We hypothesized that LQTS could be identified latently using an adverse event (AE) fingerprint of more commonly reported AEs. We aimed to generate an integrated data science pipeline that addresses current limitations by identifying latent signals for QT-DDIs in the US FDA's Adverse Event Reporting System (FAERS) and retrospectively validating these predictions using electrocardiogram data in electronic health records (EHRs). METHODS: We trained a model to identify an AE fingerprint for risk of TdP for single drugs and applied this model to drug pair data to predict novel DDIs. In the EHR at Columbia University Medical Center, we compared the QTc intervals of patients prescribed the flagged drug pairs with patients prescribed either drug individually. RESULTS: We created an AE fingerprint consisting of 13 latently detected side effects. This model significantly outperformed a direct evidence control model in the detection of established interactions (p = 1.62E-3) and significantly enriched for validated QT-DDIs in the EHR (p = 0.01). Of 889 pairs flagged in FAERS, eight novel QT-DDIs were significantly associated with prolonged QTc intervals in the EHR and were not due to co-prescribed medications. CONCLUSIONS: Latent signal detection in FAERS validated using the EHR presents an automated and data-driven approach for systematically identifying novel QT-DDIs. The high-confidence hypotheses flagged using this method warrant further investigation. PMID- 26860922 TI - Safety Profile of Atorvastatin 80 mg: A Meta-Analysis of 17 Randomized Controlled Trials in 21,910 Participants. AB - INTRODUCTION: Atorvastatin 80 mg/day has significant benefits for the primary and secondary prevention of cardiovascular and cerebrovascular disease. To our knowledge, no meta-analysis focusing on assessing the safety profile of atorvastatin 80 mg/day has been performed; therefore, our aim was to evaluate the tolerability and adverse event (AE) patterns of this drug/dose. METHODS: We conducted a search of the Cochrane Library, EMBASE and PubMed databases through to July 2015 for randomized controlled trials (RCTs). The safety endpoints included the incidence of discontinuations due to AEs, transaminase elevation, creatine kinase (CK) elevation, myalgia and rhabdomyolysis. We also conducted subgroup analyses according to the length of follow-up and clinical condition. RESULTS: Data from 17 RCTs involving 21,910 participants were included. Pooled analyses showed that atorvastatin 80 mg/day was less tolerable [risk ratio (RR) 1.29, 95 % confidence interval (CI) 1.17-1.42] and increased the risk of transaminase elevation (RR 4.59, 95 % CI 3.26-6.48) compared with controls. No significant difference was observed between the two groups in terms of the incidence of CK elevation (RR 1.38, 95 % CI 0.97-1.95), myalgia (RR 1.06, 95 % CI 0.93-1.20), and rhabdomyolysis (RR 0.67, 95 % CI 0.19-2.36). CONCLUSIONS: Patients treated with atorvastatin 80 mg/day, specifically patients with coronary artery disease (CAD), have a higher risk of transaminase elevation, which is not seen if patient exposure is less than 16 weeks. Atorvastatin 80 mg/day is less well-tolerated compared with controls, especially in patients with CAD, but an overall favorable tolerability profile is found if patient exposure is less than 52 weeks. PMID- 26860923 TI - Integrated cytogenetics and genomics analysis of transposable elements in the Nile tilapia, Oreochromis niloticus. AB - Integration of cytogenetics and genomics has become essential to a better view of architecture and function of genomes. Although the advances on genomic sequencing have contributed to study genes and genomes, the repetitive DNA fraction of the genome is still enigmatic and poorly understood. Among repeated DNAs, transposable elements (TEs) are major components of eukaryotic chromatin and their investigation has been hindered even after the availability of whole sequenced genomes. The cytogenetic mapping of TEs in chromosomes has proved to be of high value to integrate information from the micro level of nucleotide sequence to a cytological view of chromosomes. Different TEs have been cytogenetically mapped in cichlids; however, neither details about their genomic arrangement nor appropriated copy number are well defined by these approaches. The current study integrates TEs distribution in Nile tilapia Oreochromis niloticus genome based on cytogenetic and genomics/bioinformatics approach. The results showed that some elements are not randomly distributed and that some are genomic dependent on each other. Moreover, we found extensive overlap between genomics and cytogenetics data and that tandem duplication may be the major mechanism responsible for the genomic dynamics of TEs here analyzed. This paper provides insights in the genomic organization of TEs under an integrated view based on cytogenetics and genomics. PMID- 26860924 TI - Meta-analysis: The diagnostic efficacy of chromoendoscopy for early gastric cancer and premalignant gastric lesions. AB - BACKGROUND AND AIM: Chromoendoscopy (CE) is widely used in the diagnosis of early gastric cancer (EGC) and premalignant gastric lesions (PGLs). We conducted a meta analysis to evaluate the diagnostic efficacy of CE for EGC and PGLs. METHODS: We searched PubMed/MEDLINE, EMBASE, and the Cochrane library to identify all eligible studies according to inclusion and exclusion standards. Publication bias was tested using Funnel plots and Egger's test. The possible sources of the heterogeneity were explored by performing a meta-regression analysis. Heterogeneity was assessed by the Q test and I(2) statistic. RESULTS: Ten studies met the inclusion standards, including a total of 699 patients and 902 lesions. The pooled sensitivity, specificity, and area under the curve of CE were 0.90 (95% confidence interval, 0.87-0.92), 0.82 (95% confidence interval, 0.79-0.86), and 0.9464, respectively. In subgroup analysis of diagnostic accuracy, CE showed higher accuracy versus standard white light endoscopy for EGC (P = 0.005) and PGLs (P = 0.001). CONCLUSION: Chromoendoscopy seems to have a high diagnostic efficacy and improve the detection of EGC and PGLs compared with standard white light endoscopy. PMID- 26860925 TI - Utility of combined gray-scale and perflubutane contrast-enhanced ultrasound for diagnosing early hepatocellular carcinomas: Comparison of well differentiated and distinctly nodular types. AB - AIM: To clarify the value of gray-scale ultrasound (US) combined with contrast enhanced US (CEUS) with perflubutane in diagnosing early hepatocellular carcinoma (HCC). METHODS: A total of 57 surgically resected, well differentiated HCCs were analyzed. Hepatocellular carcinomas were macroscopically diagnosed as vaguely nodular or distinctly nodular types, which correspond to early HCC or progressed HCC, respectively. Gray-scale US findings were evaluated in terms of shape (round or roundish, or irregular), border and contour (well-defined and smooth, or poorly defined), and intratumor echo levels (hyper, hypo, iso, heterogeneous, or mosaic). Contrast-enhanced US findings were evaluated during the arterial phase (vascularity [finely homogeneous, dendritic, or chaotic] and perfusion enhancement [homogeneous or heterogeneous]), portal phase (presence or absence of washout), and post-vascular phase (echo intensity level [defect, incomplete defect, or iso-enhancing]). RESULTS: Eighteen HCCs were categorized as early HCCs and the remaining 39 were categorized as progressed HCCs. Receiver operating characteristic curve analysis for the diagnosis of early HCC yielded area under the receiver operating characteristic curve (Az ) values for border and contour on gray-scale US and echo intensity level in the CEUS post-vascular phase of 0.782 and 0.828, respectively. Multiple logistic regression analysis also indicated that both of these gray-scale US and CEUS findings were independently associated with early HCC. The Az value for the combination of border and contour and echo intensity for the diagnosis of early HCC was 0.907, corresponding to a high diagnostic value. CONCLUSION: The combination of gray-scale US and CEUS can provide high-quality imaging assessment for diagnosing early HCC. PMID- 26860926 TI - 2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4 methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists. AB - A series of 2-sulfonamidopyridine C-region derivatives of 2-(3-fluoro-4 methylsulfonamidophenyl)propanamide were investigated as hTRPV1 ligands. Systematic modification on the 2-sulfonamido group provided highly potent TRPV1 antagonists. The N-benzyl phenylsulfonamide derivatives 12 and 23 in particular showed higher affinities than that of lead compound 1. Compound 12 exhibited strong analgesic activity in the formalin pain model. Docking analysis of its chiral S-form 12S in our hTRPV1 homology model indicated that its high affinity might arise from additional hydrophobic interactions not present in lead compound 1S. PMID- 26860927 TI - Synthesis and biological evaluation of novel inhibitors against 1,3,8 trihydroxynaphthalene reductase from Magnaporthe grisea. AB - 1,3,8-Trihydroxynaphthalene reductase (3HNR) is an essential enzymes that is involved in fungal melanin biosynthesis. Based on the structural informations of active site of 3HNR, a series of beta-nitrostyrene compounds were rationally designed and synthesized. The enzymatic activities of these compounds showed that most of them exhibited high inhibitory activities (<5.0 MUM) against 3HNR; compound 3-2 exhibit the highest inhibitory activity (IC50=0.29 MUM). In particular, some of these compounds had moderate fungicidal activity against Magnaporthe grisea. Compound 3-4 showed high in vivo activities against M. grisea (EC50=9.5 ppm). Furthermore, compound 3-2 was selected as a representative molecule, and the probable binding mode of this compound and the surrounding residues in the active site of 3HNR was elucidated by using molecular dock. The positive results suggest that beta-nitrostyrene derivatives are most likely to be promising leads toward the discovery of novel agent of rice blast. PMID- 26860928 TI - From indole to pyrrole, furan, thiophene and pyridine: Search for novel small molecule inhibitors of bacterial transcription initiation complex formation. AB - The search for small molecules capable of inhibiting transcription initiation in bacteria has resulted in the synthesis of N,N'-disubstituted hydrazines and imine carbohydrazides comprised of indole, pyridine, pyrrole, furan and thiophene using the respective trichloroacetyl derivatives, carbohydrazides and aldehydes. Replacement of the indole moiety by smaller heterocycles linked by CONHNC linkers afforded a broad variety of compounds efficiently targeting the RNA polymerase sigma(70)/sigma(A) interaction as determined by ELISA and exhibiting increased inhibition of the growth of Escherichia coli compared to Bacillus subtilis in culture. The structural features of the synthesized transcription initiation inhibitors needed for antibacterial activity were identified employing molecular modelling and structure-activity relationship (SAR) studies. PMID- 26860929 TI - Synthesis and antibacterial evaluation of novel 4"-glycyl linked quinolyl azithromycins with potent activity against macrolide-resistant pathogens. AB - A new azithromycin-based series of antibacterial macrolones is reported, which features the use of a 4"-ester linked glycin for tethering the quinolone side chain to the macrolide scaffold. Among the analogs prepared, compounds 9e and 22f with a quinolon-6-yl moiety were found to have potent and well-balanced activity against clinically important respiratory tract pathogens, including erythromycin susceptible and MLSB resistant strains of Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae. In addition, potential lead compounds 9e and 22f demonstrated outstanding levels of activity against Moraxella catarrhalis and inducibly MLSB resistant Staphylococcus aureus. The best member of this series 22f rivals or exceeds, in potency, some of the most active ketolide antibacterial agents known today, such as telithromycin and cethromycin. PMID- 26860930 TI - Thermodynamics and Structural Evolution during a Reversible Vesicle-Micelle Transition of a Vitamin-Derived Bolaamphiphile Induced by Sodium Cholate. AB - Interaction of endogenous sodium cholate (SC) with dietary amphiphiles would induce structural evolution of the self-assembled aggregates, which inevitably affects the hydrolysis of fat in the gut. Current work mainly focused on the interaction of bile salts with classical double-layered phospholipid vesicles. In this paper, the thermodynamics and structural evolution during the interaction of SC with novel unilamellar vesicles formed from vitamin-derived zwitterionic bolaamphiphile (DDO) were characterized. It was revealed that an increased temperature and the presence of NaCl resulted in narrowed micelle-vesicle coexistence and enlarged the vesicle region. The coexistence of micelles and vesicles mainly came from the interaction of monomeric SC with DDO vesicles, whereas micellar SC contributed to the total solubilization of DDO vesicles. This research may enrich the thermodynamic mechanism behind the structure transition of the microaggregates formed by amphiphiles in the gut. It will also contribute to the design of food formulation and drug delivery system. PMID- 26860931 TI - Development of safe, effective and immunogenic vaccine candidate for diarrheagenic Escherichia coli main pathotypes in a mouse model. AB - BACKGROUND: Enteric and diarrheal diseases are important causes of childhood death in the developing world. These diseases are responsible for more than 750 thousand deaths in children under 5 years old worldwide, ranking second cause of death, after lower respiratory diseases, in this age group. Among the major causative agents of diarrhea is Escherichia coli. There are several vaccine trials for diarrheagenic E. coli. However, diarrheagenic E. coli has seven pathotypes and vaccines are directed for one or two of the five main pathotypes causing diarrhea. Currently, there are no combined vaccines available in the market for all five diarrheagenic E. coli pathotypes. Therefore, we aimed to develop a low-cost vaccine candidate combining the five main diarrheagenic E. coli to offer wide-spectrum protection. We formulated a formalin-killed whole cell mixture of enteroaggregative, enteropathogenic, enteroinvasive, enterohemorrhagic, and enterotoxigenic E. coli pathotypes as a combined vaccine candidate. RESULTS: We immunized Balb/C mice subcutaneously with 10(9) CFU of combined vaccine candidate and found a significant increase in survival rate post challenge compared to unimmunized controls (100 % survival). Next we aimed to determine the immunological response of mice to the combined vaccine candidate compared to each pathotype immunization. To do so, we immunized mice groups with combined vaccine candidate and monitored biomarkers levels over 6 weeks as well as measured responses post challenge with relevant living E. coli. We found significant increase in specific systemic antibodies (IgG), interferon gamma (IFNgamma) and interleukin 6 (IL-6) levels elicited by combined vaccine candidate especially in the first 2 weeks after mice immunization compared to controls (p < 0.05). We also evaluated alum and cholera toxin B subunit (CTB) as potential adjuvant systems for our candidate vaccine. We found that CTB-adjuvanted combined vaccine candidate showed significantly higher IgG and IFNgamma levels than alum. CONCLUSIONS: Overall, our combined vaccine candidate offered protection against the five main diarrheagenic E. coli pathotypes in a single vaccine using mouse model. To the best of our knowledge, this is the first combined vaccine against the five main diarrheagenic E. coli pathotypes that is cost-effective with promise for further testing in humans. PMID- 26860932 TI - Complications and Surveillance After Bariatric Surgery. AB - OPINION STATEMENT: Bariatric surgery represents a durable and safe treatment modality for morbid obesity. Bariatric surgery results in weight loss by one of two-and possibly both-primary mechanisms, reducing the amount of tolerable intake (restrictive) and reducing the amount of nutrients absorbed by bypassing absorptive intestine (malabsorptive). These procedures have consistently demonstrated superior resolution of obesity and many associated co-morbid conditions as compared to medical management. Beyond the periprocedural complications of surgery, there are longitudinal risks such as weight regain, anatomic complications, and micronutrient deficiencies. Complications related to the anatomic alteration after bariatric surgery include internal herniation, marginal ulcers, dumping syndrome, and gastric band-related complications. Physicians who take care of bariatric patients at any point in their post operative care must be vigilant for these complications, as they may necessitate urgent intervention or re-operation. Micronutrient deficiencies, which commonly occur after malabsorptive procedures, may present with a wide range of symptoms including neuropathies, anemia, poor wound healing, and hair loss, among others. Deficiencies of vitamins and minerals frequently result in the need for long-term supplementation and may necessitate intravenous repletion when severe. Bariatric surgery may also alter the absorption of commonly prescribed medications, including anti-psychotic medications. PMID- 26860933 TI - A multidisciplinary view on cultural primatology: behavioral innovations and traditions in Japanese macaques. AB - Cultural primatology (i.e., the study of behavioral traditions in nonhuman primates as a window into the evolution of human cultural capacities) was founded in Japan by Kinji Imanishi in the early 1950s. This relatively new research area straddles different disciplines and now benefits from collaborations between Japanese and Western primatologists. In this paper, we return to the cradle of cultural primatology by revisiting our original articles on behavioral innovations and traditions in Japanese macaques. For the past 35 years, our international team of biologists, psychologists and anthropologists from Japan, France, Sri Lanka, the USA and Canada, has been taking an integrative approach to addressing the influence of environmental, sociodemographic, developmental, cognitive and behavioral constraints on the appearance, diffusion, and maintenance of behavioral traditions in Macaca fuscata across various domains; namely, feeding innovation, tool use, object play, and non-conceptive sex. PMID- 26860934 TI - Unusual sleeping site selection by southern bamboo lemurs. AB - Selection of sleeping sites has consequences for individual fitness. Non-human primates often bias their selection towards arboreal sites, and the lemurs of Madagascar typically rest/sleep in trees, tree holes, and/or constructed nests. Three non-mutually exclusive hypotheses to explain sleeping site selection include protection from predators, avoidance of parasitic vectors, and improved thermoregulation. Here, we examine these hypotheses for the unusual sleeping site selections by the southern bamboo lemur (Hapalemur meridionalis). Within the Mandena littoral forest of southeast Madagascar, the southern bamboo lemur is known for its ecological flexibility compared to other bamboo lemur species, including a dietary niche expansion to feeding on the ground. Between October 2012 and December 2013, we observed bamboo lemurs from three social groups for 1778.67 h, conducting full-day focal follows on 11 adult individuals (five males, six females). During this period, all three groups were observed to sleep on the ground, with one of these groups also using an abandoned nest of a Madagascar crested ibis (Lophotibis cristata). We collected habitat and temperature data to examine whether selection was influenced by environmental variables. Terrestrial sleeping (N = 17) was observed in all individuals but one adult female, with individuals burrowing under thick vegetation more often during the hot austral summer. While difficult to rigorously test, it is possible that terrestrial sleep sites and/or sleeping in a bird nest may impair visual detection by some aerial and terrestrial predators. Neither of these sites (i.e., terrestrial sleeping or use of a bird nest), however, is likely to minimize exposure to parasites/vectors. Terrestrial sleeping appears to support a thermoregulatory strategy, whereas the use of a bird nest could not be empirically tested. Our observations of unique sleeping site locations used by southern bamboo lemurs further the complexity of their natural history and that of Malagasy strepsirrhines. PMID- 26860935 TI - A Calcitonin Non-producing Neuroendocrine Tumor of the Thyroid Gland. AB - Neuroendocrine tumors of the thyroid gland are generally considered to derive from parafollicular endocrine cells (C cells) and are generally referred to as medullary thyroid carcinomas (MTC). Calcitonin secretion is almost always detected in MTC and a prerequisite for both clinical and pathological diagnosis. Thyroid neuroendocrine tumors without any apparent calcitonin secretion reflect a diagnostic dilemma because non-calcitonin-producing MTCs have virtually not been characterized. Here, we report a case of primary thyroid neuroendocrine tumors lacking calcitonin secretion or expression. The tumor cells expressed cytokeratins, chromogranin A, and synaptophysin, all of which were consistent with epithelial and neuroendocrine differentiation. Thyroid transcription factor 1 paired box gene 8, and carcinoembryonic antigen were also immunohistochemically detected, consistent with its thyroid origin. However, the tumor was negative for calcitonin both by immunohistochemistry and in situ hybridization, hence, not meeting the definition of MTC. Despite the loss of calcitonin expression, immunoreactivity for the calcitonin-gene-related peptide was detected in the tumor. Somatic gene mutations of RET, H-RAS, K-RAS, or BRAF were not detected in this case. A limited number of calcitonin non-producing thyroid neuroendocrine tumors are available in the scientific literature available in English, and its etiology and clinical manifestations remain largely unknown. Our case, along with the rare, previously reported cases, suggests that calcitonin non-producing neuroendocrine tumors of the thyroid gland are most likely derived from C cells, but should be differentiated from ordinary MTCs. PMID- 26860936 TI - Clinical Impact of the Current WHO Classification of Pituitary Adenomas. AB - WHO classifications should be used for comparing the results from different groups of pathologist and clinicians by standardized histopathological methods. Our present report describes the important parameters of pituitary adenoma pathology as demand of the WHO classification for correlation to endocrine data and prognosis. The combination of HE stain based structures with immunostainings for pituitary hormones allows subclassification of adenomas as the best method not only for correlations to clinical hyperfunctions but also for statements to the sensitivity of drug therapies (somatostatin analogs, dopamine agonists). GH-, PRL- and ACTH-secreting pituitary adenomas are further classified based on the size and number of their secretory granules by electron microscopy, or as is mostly the case nowadays by cytokeratin staining pattern, into densely and sparsely granulated. Granulation pattern may be considered for the prediction of treatment response in patients with GH-secreting adenomas, since the sparsely granulated subtype was shown to be less responsive to somatostatin analog treatment. For prognosis, it is important to identify aggressive adenomas by measurements of the Ki-67 index, of the number of mitoses, and of nuclear expression of p53. Among the criteria for atypical adenomas, high Ki-67 labeling index and invasive character are the most important adverse prognostic factors. Promising molecular markers have been identified that might supplement the currently used proliferation parameters. For defining atypical adenomas in a future histopathological classification system, we propose to provide the proliferative potential and the invasive character separately. PMID- 26860937 TI - Inter-day reliability of blood pressure and cerebral blood flow velocities in persons with spinal cord injury and intact controls. AB - BACKGROUND: Due to interruption of cardiovascular autonomic control unstable blood pressure (BP) is common in individuals with spinal cord injury (SCI) above the sixth thoracic vertebral level. The impact of unstable BP on cerebral blood flow (CBF) is not well appreciated, but symptoms associated with altered cerebral perfusion are reported, which can negatively impact daily life activities. METHODS: We measured seated BP and CBF in participants with SCI and able-bodied (AB) controls on three laboratory visits to determine the inter-day reliability (intraclass correlation coefficient: ICC). BP was assessed at the finger using photoplethysmography and at the brachial artery with manual sphygmomanometry. CBF velocities (CBFv) were assessed at the middle cerebral artery using transcranial Doppler (TCD) ultrasound. RESULTS: Data were collected in 15 participants with chronic SCI (C3-T4) and 10 AB controls, the groups did not differ for age, height, weight or BMI; however, brachial BP (P < 0.001), finger BP (P < 0.01) and CBFv (P < 0.05) were significantly lower in the SCI group compared to the controls. The inter-day ICC for brachial BP ranged from 0.51 to 0.79, whereas the ICC for finger BP was not as high (0.17 to 0.47). The inter-day ICC for CBFv ranged from 0.45 to 0.96, indicating fair to substantial reliability. CONCLUSIONS: These data indicate good inter-day reliability of brachial BP and TCD recording of CBFv; however, the assessment of finger BP appears to be somewhat less reliable. In addition, these data confirm reduced resting CBFv in association with hypotension in individuals with SCI compared to matched controls with low BP. PMID- 26860938 TI - Enhancement of astaxanthin production using Haematococcus pluvialis with novel LED wavelength shift strategy. AB - Haematococcus pluvialis is a green microalga of particular interest, since it is considered the best potential natural source of astaxanthin, which is widely used as an additive for natural pigmentation. In addition, astaxanthin has recently garnered commercial interest as a nutraceutical, cosmetic, and pharmaceutical. However, producing astaxanthin from H. pluvialis necessitates separation with distinctive culture conditions, dividing between the microalgae growth and the astaxanthin production stages. Light-emitting diodes (LEDs) have emerged as a replacement for traditional light sources, and LED applications are now rapidly expanding to multiple areas in fields such as biotechnology. However, further detail application into microalgae biotechnology remains limited. In this study, we have attempted to establish new protocols based on the specific wavelength of LEDs for the cultivation and production of astaxanthin using H. pluvialis. Specifically, we applied red LEDs for microalgae cell growth and then switched to blue LEDs to induce astaxanthin biosynthesis. The result showed that astaxanthin productions based on a wavelength shift from red to blue were significantly increased, compared to those with continuous illumination using red LEDs. Furthermore, additional increase of astaxanthin production was achieved with simultaneous application of exogenous carbon with blue LED illumination. Our approach based on the proper manipulation of LED wavelengths upon H. pluvialis cell stages will enable the improvement of biomass and enhance astaxanthin production using H. pluvialis. PMID- 26860939 TI - Removal of phenol in phenolic resin wastewater by a novel biomaterial: the Phanerochaete chrysosporium pellet containing chlamydospore-like cells. AB - A novel biomaterial, the Phanerochaete chrysosporium pellet (CP) composed of chlamydospore-like cells (CLCs), was prepared and its potential in treating phenolic resin wastewater was evaluated. CP possesses higher phenol removal ability in contrast with mycelial pellets of P. chrysosporium, and CLC can be seen as the naturally immobilized enzymes. At shake-flask level, the ideal pH value, temperature, and inoculation quantity of CP for treatment of 1430 mg/l phenol wastewater were pH 4-6, 30 degrees C, and 5.0 g/l, respectively, and the maximum specific removal rate, 41.1 mg phenol/g CP/h, was obtained in fixed bed reactor (FBR) when the flow rate of wastewater was 3.4 l/h. During the treatment, FBR harbored amounts of bacteria (135 genera) and eukaryotes, as analyzed by metagenomic sequencing. Bacterial pollution not only decreased reactor performance but also had a negative impact on reusability of CP. Hot water treatment (80-85 degrees C) is effective to inhibit bacterial pollution, and heat resistance of CLC makes the repeated regrowing of CP be feasible. This work presents an innovative and low-cost biomaterial for phenol removal and will be helpful for the practical application of P. chrysosporium in wastewater treatment. PMID- 26860940 TI - Advances in time course extracellular production of human pre-miR-29b from Rhodovulum sulfidophilum. AB - The present study reports the successful production of human pre-miR-29b both intra- and extracellularly in the marine phototrophic bacterium Rhodovulum sulfidophilum using recombinant RNA technology. In a first stage, the optimal transformation conditions (0.025 MUg of plasmid DNA, with a heat-shock of 2 min at 35 degrees C) were established, in order to transfer the pre-miR-29b encoding plasmid to R. sulfidophilum host. Furthermore, the extracellular recovery of this RNA product from the culture medium was greatly improved, achieving quantities that are compatible with the majority of applications, namely for in vitro or in vivo studies. Using this system, the extracellular human pre-miR-29b concentration was approximately 182 MUg/L, after 40 h of bacterial growth, and the total intracellular pre-miR-29b was of about 358 MUg/L, at 32 h. At the end of the fermentation, it was verified that almost 87 % of cells were viable, indicating that cell lysis is minimized and that the extracellular medium is not highly contaminated with the host intracellular ribonucleases (RNases) and endotoxins, which is a critical parameter to guarantee the microRNA (miRNA) integrity. These findings demonstrate that pre-miRNAs can be produced by recombinant RNA technology, offering novel clues for the production of natural pre-miRNA agents for functional studies and RNA interference (RNAi)-based therapeutics. PMID- 26860941 TI - Genetic regulation and manipulation for natural product discovery. AB - Natural products are an important source of modern medical development, e.g., antibiotics, anticancers, immune modulators, etc. and will continue to be a powerful driving force for the discovery of novel potential drugs. In the heterologous hosts, natural products are biosynthesized using dedicated metabolic networks. By gene engineering, pathway reconstructing, and enzyme engineering, metabolic networks can be modified to synthesize novel compounds containing enhanced structural feature or produce a large quantity of known valuable bioactive compounds. The review introduces some important technical platforms and relevant examples of genetic regulation and manipulation to improve natural product titers or drive novel secondary metabolite discoveries. PMID- 26860943 TI - Understanding the antimicrobial activity behind thin- and thick-rolled copper plates. AB - The aim of this study was to compare the antibacterial properties of the surfaces of copper plates that were rolled to a thickness of 25 and 100 MUm. Differences in topology of 25- and 100-MUm-thick copper plates were studied using scanning electron microscopy (SEM), atomic force microscopy (AFM), and X-ray diffraction (XRD). Antibacterial activity of the copper surfaces was tested against strains of Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Listeria monocytogenes, Salmonella typhimurium, Streptococcus sp. BY1, Enterococcus sp. BY2, and Bacillus cereus BY3. Changes in viable cell numbers were determined by plating onto optimal growth media and staining with LIVE/DEAD BacLightTM. Changes in metabolic activity were recorded by expression of the luciferase (lux) gene. Cell morphology was studied using SEM. Accumulation and diffusion of copper from cells were recorded using inductively coupled plasma mass spectroscopy (ICP-MS). Lipid and protein oxidation were recorded spectrophotometrically. Surfaces of 25-MUm-thick copper plates were rough compared to that of 100-MUm-thick copper plates. For most species, a five-log reduction in cell numbers, cell membrane instability, and a decline in metabolic activity were recorded after 15 min of exposure to 25-MUm-thick copper plates. Copper accumulated in the cells, and lipids and proteins were oxidized. The rough surface of thinner copper plates (25 MUm thick) released more copper and was more antimicrobial compared to thicker (100 MUm) copper plates. Cell death was attributed to destabilization of the cell membrane, lipid peroxidation, and protein oxidation. PMID- 26860944 TI - Genetic basis and importance of metal resistant genes in bacteria for bioremediation of contaminated environments with toxic metal pollutants. AB - Metal pollution is one of the most persistent and complex environmental issues, causing threat to the ecosystem and human health. On exposure to several toxic metals such as arsenic, cadmium, chromium, copper, lead, and mercury, several bacteria has evolved with many metal-resistant genes as a means of their adaptation. These genes can be further exploited for bioremediation of the metal contaminated environments. Many operon-clustered metal-resistant genes such as cadB, chrA, copAB, pbrA, merA, and NiCoT have been reported in bacterial systems for cadmium, chromium, copper, lead, mercury, and nickel resistance and detoxification, respectively. The field of environmental bioremediation has been ameliorated by exploiting diverse bacterial detoxification genes. Genetic engineering integrated with bioremediation assists in manipulation of bacterial genome which can enhance toxic metal detoxification that is not usually performed by normal bacteria. These techniques include genetic engineering with single genes or operons, pathway construction, and alternations of the sequences of existing genes. However, numerous facets of bacterial novel metal-resistant genes are yet to be explored for application in microbial bioremediation practices. This review describes the role of bacteria and their adaptive mechanisms for toxic metal detoxification and restoration of contaminated sites. PMID- 26860945 TI - Combinatorial biosynthesis of Synechocystis PCC6803 phycocyanin holo-alpha subunit (CpcA) in Escherichia coli and its activities. AB - In order to investigate the feasibility for the biosynthetic pathway of CpcA conjugated protein to be reconstituted in Escherichia coli and its antioxidant ability and protective effect on the growth of E. coli, the minimal biosynthetic pathway in cyanobacteria leading from heme to the formation of the cysteinyl residue of phycocyanobilin with deprosthetic CpcA was reconstituted in E. coli using a relatively simple and effective method. When the constructed plasmid pETDuet-6 bearing five genes involved in the biosynthesis of CpcA was transformed into E. coli, the screened transformant acquired a pronounced blue color. Visualization of proteins on SDS-PAGE gel showed a 29 kDa distinct band, corresponding to the theoretically calculated molecular weight of CpcA. Upon exposure to Zn(2+) and UV illumination, the CpcA band was fluorescent. Western blot analysis using His-tag monoclonal antibody confirmed the expression of CpcA in the recombinant E. coli. After the optimization of critical medium components by response surface methodology, the recombinant cells produced 22.29 mg/l of CpcA. The recombinant CpcA displayed a strong ability to scavenge three free radicals .OH, .DPPH, and O2 (-) to protect against the oxidation of linoleic acid and to restore the growth of E. coli cells injured by DPPH and H2O2 at a relatively low concentration. These results lay a good foundation for the production and future use of CpcA. PMID- 26860946 TI - 14q22.3 Microdeletion encompassing OTX2 in a five-generation family with microphthalmia, pituitary abnormalities, and intellectual disability. PMID- 26860942 TI - Bacteriocins of lactic acid bacteria: extending the family. AB - Lactic acid bacteria (LAB) constitute a heterogeneous group of microorganisms that produce lactic acid as the major product during the fermentation process. LAB are Gram-positive bacteria with great biotechnological potential in the food industry. They can produce bacteriocins, which are proteinaceous antimicrobial molecules with a diverse genetic origin, posttranslationally modified or not, that can help the producer organism to outcompete other bacterial species. In this review, we focus on the various types of bacteriocins that can be found in LAB and the organization and regulation of the gene clusters responsible for their production and biosynthesis, and consider the food applications of the prototype bacteriocins from LAB. Furthermore, we propose a revised classification of bacteriocins that can accommodate the increasing number of classes reported over the last years. PMID- 26860948 TI - MED12 exon 2 mutation as a highly sensitive and specific marker in distinguishing phyllodes tumours from other spindle neoplasms of the breast. AB - Spindle neoplasms of the breast (SNB) primarily include metaplastic breast carcinoma (MBC), phyllodes tumour (PT), fibromatosis and primary nonspecific sarcoma (PNS). Mutations in MED12 exon 2 have been reported in PTs. Because spindle tumour components are shared by SNB, we assessed the diagnostic use of MED12 exon 2 mutation in SNB. We investigated MED12 exon 2 mutations in a total of 91 samples of SNB, including 49 PT cases that have been previously analysed. Mutations were identified using direct sequencing. MED12 exon 2 mutation was absent in all cases of MBC, fibromatosis and PNS, in contrast to the 71.4% positivity in PTs. MED12 mutations were identified in four of six previously diagnosed monophasic sarcomatous MCB cases, however, these four cases were revised as malignant PT based on additional bcl-2 staining, albeit very focal. Consistence in the MED12 mutational status between a paired core biopsy and a surgical specimen was observed in all 20 tested PT cases. In conclusion, we demonstrated the restriction of MED12 exon 2 mutation to PTs (73.6%, 39/53) and its absence in other SNB. MED12 exon 2 mutational analysis can be included in the differential diagnosis between PT and other SNB, especially with limited specimen where diagnostic clues are not evident. PMID- 26860947 TI - Effective treatment of HER2-amplified breast cancer by targeting HER3 and beta1 integrin. AB - The central role of HER2 as the disease driver and HER3 as its essential partner has made them rational targets for the treatment of HER2-amplifed breast cancers, and there is considerable interest in developing highly effective treatment regimens for this disease that consist of targeted therapies alone. Much of these efforts are focused on dual targeting approaches, particularly dual targeting of the HER2-HER3 tumor driver complex itself, or vertical combinations that target downstream PI3K or Akt in addition to HER2. There is also potential in lateral combinations based on evidence implicating cross-talk with other membrane receptor systems, particularly integrins, and such lateral combinations can potentially involve either HER2 or HER3. We established a preclinical model of targeting HER3 using doxycycline-inducible shRNA and determined the efficacy of a beta1 integrin inhibitor in combination with targeting HER3. We report that targeting HER3 and beta1 integrin provides a particularly effective combination therapy approach for HER2-amplified cancers, surpassing the combination of HER2 and beta1 integrin targeting, and evading some of the safety concerns associated with direct HER2-targeting. This further validates HER3 as a major hub mediating the tumorigenic functions of HER2 and identifies it as a high value target for lateral combination therapy strategies. PMID- 26860949 TI - Physical compared to mental diseases as reasons for committing suicide: a retrospective study. AB - BACKGROUND: Several studies investigated the relationship between mental disorders and suicidal ideation. However, little is known about physical illnesses being the major trigger for committed suicides. It is necessary to understand these risk factors to be able to meet the needs of patients in a palliative care setting. METHODS: Suicide, medical and police notes were retrospectively analysed from all autopsies conducted in 2009-11 at the University of Munich, Germany. Documented reasons for suicide were classified into a "physical disease" (PD) or "mental disease" (MD) group and compared with respect to their sociodemographic characteristics and autopsy outcomes. RESULTS: Of all 1069 cases, 18.9% gave a PD as reason for committing suicide (MD, 32.7%). Those indicating PD were older than MD (68.8 vs. 48.7 years; p < 0.001) with more men being in this group (72.8% vs. 59.1%; p=0.002). In PD, 30.7% suffered from cancer, 28.7% from chronic pain and 12.4% from lung disease. 38.8% of MD and 12.4% of PD had previous suicide attempts. CONCLUSIONS: In palliative care, it is necessary to screen patients on a regular basis for suicidal ideation, especially those with previous suicide attempts. PMID- 26860950 TI - Schrodinger's scat: a critical review of the currently available tiger (Panthera Tigris) and leopard (Panthera pardus) specific primers in India, and a novel leopard specific primer. AB - BACKGROUND: Non-invasive sampling has opened avenues for the genetic study of elusive species, which has contributed significantly to their conservation. Where field based identity of non-invasive sample is ambiguous (e.g. carnivore scats), it is essential to establish identity of the species through molecular approaches. A cost effective procedure to ascertain species identity is to use species specific primers (SSP) for PCR amplification and subsequent resolution through agarose gel electrophoresis. However, SSPs if ill designed can often cross amplify non-target sympatric species. Herein we report the problem of cross amplification with currently published SSPs, which have been used in several recent scientific articles on tigers (Panthera tigris) and leopards (Panthera pardus) in India. Since these papers form pioneering research on which future work will be based, an early rectification is required so as to not propagate this error further. RESULTS: We conclusively show cross amplification of three of the four SSPs, in sympatric non-target species like tiger SSP amplifying leopard and striped hyena (Hyaena hyaena), and leopard SSP amplifying tiger, lion (Panthera leo persica) and clouded leopard (Neofelis nebulosa), with the same product size. We develop and test a non-cross-amplifying leopard specific primer pair within the mitochondrial cytochrome b region. We also standardize a duplex PCR method to screen tiger and leopard samples simultaneously in one PCR reaction to reduce cost and time. CONCLUSIONS: These findings suggest the importance of an often overlooked preliminary protocol of conclusive identification of species from non-invasive samples. The cross amplification of published primers in conspecifics suggests the need to revisit inferences drawn by earlier work. PMID- 26860951 TI - Exosomes: potential for early detection in pancreatic cancer. AB - Progress in the treatment of patients with pancreatic cancer at earlier stages has motivated research in identifying novel noninvasive or minimally invasive biomarkers for early detection. Exosomes, which contain bioactive molecules (such as proteins, RNAs and lipids), are membrane-structured nanovesicles that are secreted from living cells and are found in human body fluids. As functional mediators, exosomes play key roles in cell-cell communications, regulating diverse biological processes. Here we aim to examine recent findings in the potential diagnostic value of serum exosomes in pancreatic cancer. PMID- 26860952 TI - Capabilities and Characteristics of Digital Measurement Feedback Systems: Results from a Comprehensive Review. AB - Measurement feedback systems (MFS) are a class of health information technology (HIT) that function as an implementation support strategy for integrating measurement based care or routine outcome monitoring into clinical practice. Although many MFS have been developed, little is known about their functions. This paper reports findings from an application of health information technology academic and commercial evaluation (HIT-ACE), a systematic and consolidated evaluation method, to MFS designed for use in behavioral healthcare settings. Forty-nine MFS were identified and subjected to systematic characteristic and capability coding. Results are presented with respect to the representation of characteristics and capabilities across MFS. PMID- 26860953 TI - Fostering Psychotropic Medication Oversight for Children in Foster Care: A National Examination of States' Monitoring Mechanisms. AB - To describe state responses to psychotropic medication safety concerns among children in foster care, this study proposes a taxonomy for state-level psychotropic medication monitoring mechanisms and highlights state variations. Seventy-two key informants, representing state child-serving agencies within the 50 states and DC, completed semi-structured interviews. We employed modified grounded theory to develop the taxonomy, and then generated state-specific summaries that were validated by key informants. Nationally, 88.2 % of the states employed at least one of seven mechanisms. For the most frequently implemented mechanisms (collegial secondary review, prior authorization, database review), over half were implemented between January 2011 and July 2013. PMID- 26860954 TI - Erratum to: Linc00152 promotes proliferation in gastric cancer through the EGFR dependent pathway. PMID- 26860955 TI - Parkinson's disease: acid-glucocerebrosidase activity and alpha-synuclein clearance. AB - The role of mutations in the gene GBA1 encoding the lysosomal hydrolase beta glucocerebrosidase for the development of synucleinopathies, such as Parkinson's disease and dementia with Lewy bodies, was only very recently uncovered. The knowledge obtained from the study of carriers or patients suffering from Gaucher disease (a common lysosomal storage disorder because of GBA1 mutations) is of particular importance for understanding the role of the enzyme and its catabolic pathway in the development of synucleinopathies. Decreased activity of beta glucocerebrosidase leads to lysosomal dysfunction and the accumulation of its substrate glucosylceramide and related lipid derivatives. Glucosylceramide is suggested to stabilize toxic oligomeric forms of alpha-synuclein that negatively influence the activity of beta-glucocerebrosidase and to partially block export of newly synthesized beta-glucocerebrosidase from the endoplasmic reticulum to late endocytic compartments, amplifying the pathological effects of alpha synuclein and ultimately resulting in neuronal cell death. This pathogenic molecular feedback loop and most likely other factors (such as impaired endoplasmic reticulum-associated degradation, activation of the unfolded protein response and dysregulation of calcium homeostasis induced by misfolded GC mutants) are involved in shifting the cellular homeostasis from monomeric alpha synuclein towards oligomeric neurotoxic and aggregated forms, which contribute to Parkinson's disease progression. From a therapeutic point of view, strategies aiming to increase either the expression, stability or delivery of the beta glucocerebrosidase to lysosomes are likely to decrease the alpha-synuclein burden and may be useful for an in depth evaluation at the organismal level. Lysosomes are critical for protein and lipid homeostasis. Recent research revealed that dysfunction of this organelle contributes to the development of neurodegenerative diseases such as Parkinson's disease (PD). Mutations in the lysosomal hydrolase beta-glucocerebrosidase (GBA1) are a major risk factor for the development of PD and the molecular events linked to the reduced activity of GBA1 and the pathological accumulation of lipids and alpha-synuclein are just at the beginning to be understood. New therapeutic concepts in regards to how to increase the expression, stability, or delivery of beta-glucocerebrosidase to lysosomes are currently developed. This article is part of a special issue on Parkinson disease. PMID- 26860956 TI - Comparison of diagnostic evaluations for cough among initiators of angiotensin converting enzyme inhibitors and angiotensin receptor blockers. AB - PURPOSE: Differential diagnostic evaluation associated with a drug may bias effect estimates because of an increased detection of preclinical outcomes. Persistent cough is a common side effect with angiotensin-converting enzyme inhibitors (ACEI), and we hypothesized that ACEI initiators would undergo more diagnostic evaluations, potentially leading to diagnosis of preclinical lung cancer. We compared the incidence of cough-related diagnostic evaluations and lung cancer among ACEI versus angiotensin receptor blockers (ARB) initiators. METHODS: Using a 20% sample of Medicare claims 2007-2012, we identified initiators of ACEI or ARB, age 66-99 years. Incidence of diagnostic evaluation and lung cancer were compared using adjusted Cox models. Monthly probabilities of workup were compared using proportion differences. RESULTS: There were 342 611 and 108 116 ACEI and ARB initiators, respectively. Monthly probability of chest X rays ranged from minimum 4.7% to maximum 21.2% in the 6 months pre and post initiation. Differences in incidence of diagnostic procedures in the 6 months after initiation were only minimal (chest X-rays hazard ratio (HR) = 1.12; 95% CI: 1.10-1.14), chest-MRI (0.86, 95% CI: 0.74-0.99), CT-scans (1.09, 95% CI: 0.99 1.18) or bronchoscopies (1.03, 95% CI: 0.83-1.29). Proportion differences for chest X-rays peaked in the month pre-initiation (8.4%, 95% CI: 8.1-8.6) but negligible thereafter. There was no difference in the incidence of lung cancer among ACEI versus ARB initiators (HR = 0.99, 95% CI: 0.84-1.16). CONCLUSION: Results indicate minimal differential chest workup after ACEI versus ARB initiation and no difference in lung cancer incidence, but suggest differential workup in the month before the first recorded prescription. The latter may reflect drug use before the first observed pharmacy claim or increased workup before initiation of ACEI therapy. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26860957 TI - Hyperglycemia-induced inflammation caused down-regulation of 8-oxoG-DNA glycosylase levels in murine macrophages is mediated by oxidative-nitrosative stress-dependent pathways. AB - High glucose-induced increase in production of reactive oxygen/nitrogen species (ROS/RNS) is recognized as a major cause of the clinical complications associated with diabetes. ROS/RNS apart from being redox agents, cause an unwanted severe physiological load to cells, also act as cellular messengers, and play a key role in activation of circulating macrophages. However, the molecular mechanisms of activation of macrophages by hyperglycemic conditions are currently unclear. In the present study, we report that high glucose (HG) causes a dramatic increase in the production of inflammatory cytokines and chemokines, at least in part through enhanced mRNA transcription. The increase in levels of inflammatory cytokines/chemokines corresponds to increased levels of ROS/RNS, which is accompanied by increased activities of Akt, ERK1/2, tuberin, down regulation of 8 oxoG-DNA glycosylase (OGG1), and increase in 8-hydroxydeoxyguanosine (8-OHdG) accumulation in DNA. Elevated levels of ROS/RNS are triggering alteration in antioxidants level, biomolecules damage, cell cycle dysregulation, and apoptosis in macrophage cells. Pretreatment of antioxidants caused decrease in the levels of ROS/RNS leads to an increase in the levels of antioxidants, decrease in biomolecules damage, alterations in Akt, ERK1/2, tuberin, upregulation of OGG1, and decrease in 8-OHdG accumulations in DNA. Further, antioxidants treatments inhibit the effects of HG on the transcriptional activity of cytokines and chemokines. Our results demonstrate that intracellular signaling pathways mediated by ROS/RNS are linked to each other by elevated glucose in macrophages activation leading to inflammation. These findings provide a mechanistic explanation of how ROS/RNS cooperate to conduct inflammatory intracellular signals in macrophages related complications in hyperglycemic conditions. PMID- 26860959 TI - R132H mutation in IDH1 gene reduces proliferation, cell survival and invasion of human glioma by downregulating Wnt/beta-catenin signaling. AB - Mutations in the isocitrate dehydrogenase 1 (IDH1) gene commonly occur in gliomas. Remarkably, the R132H mutation in IDH1 (IDH1-R132H) is associated with better prognosis and increased survival than patients lacking this mutation. The molecular mechanism underlying this phenomenon is largely unknown. In this study, we investigated potential cross-talk between IDH1-R132H and Wnt/beta-catenin signaling in regulating the cellular properties of human glioma. Although aberrant nuclear accumulation of beta-catenin is linked to the malignant progression of gliomas, its association with IDH1 remains unknown. We identified an inverse correlation between IDH1-R132H and the expression and activity of beta catenin in human gliomas. In addition, overexpression of IDH1-R132H in glioblastoma cell lines U87 and U251 led to reduced cell proliferation, migration and invasion, accompanied by increased apoptosis. At the molecular level, we detected a significant reduction in the expression, nuclear accumulation and activity of beta-catenin following overexpression of IDH1-R132H. A microarray based comparison of gene expression indicated that several mediators, effectors and targets of Wnt/beta-catenin signaling are downregulated, while negative regulators are upregulated in IDH1-R132H gliomas. Further, overexpression of beta catenin in IDH1-R132H glioma cells restored the cellular phenotype induced by this mutation. Specifically, beta-catenin abrogated the decrease in proliferation, invasion and migration, and the increase in apoptosis, triggered by overexpression of IDH1-R132H. Finally, we demonstrate that xenografts of IDH1 R132H overexpressing U87 cells can significantly decrease the growth of tumors in vivo. Altogether, our results strongly suggest that the R132H mutation in IDH1 serves a tumor suppressor function in human glioma by negatively regulating Wnt/beta-catenin signaling. PMID- 26860960 TI - Interagency collaboration in children and young people's mental health: a systematic review of outcomes, facilitating factors and inhibiting factors. AB - BACKGROUND: In the UK and internationally, there have been increasing calls for interagency collaboration across mental health services for children and young people. However, it is not clear whether such practices do, indeed, have a positive impact and, if so, what factors facilitate and inhibit collaboration across agencies. METHODS: Electronic searches were carried out on seven key computerized bibliographic databases. For inclusion in the review, studies needed to report on close working by two or more services that provided mental health support for children and/or young people and that had some systematic collection of qualitative and/or quantitative data. Outcomes were analysed narratively, and facilitating and inhibiting factors were examined using thematic analysis. RESULTS: A final sample of 33 studies was identified from 4136 initial records. Outcomes were mixed, with some findings indicating that interagency collaboration was associated with greater service use and equity of service provision, but other suggesting negative outcomes on service use and quality. However, interagency collaboration was perceived as helpful and important by both service users and professionals, and collaborative initiatives were evaluated positively. The factors most commonly identified as facilitating interagency collaboration were good interagency communication, joint trainings, good understandings across agencies, mutual valuing across agencies, senior management support, protocols on interagency collaboration and a named link person. The most commonly perceived barriers to interagency collaboration were inadequate resourcing, poor interagency communication, lack of valuing across agencies, differing perspectives, poor understandings across agencies and confidentiality issues. CONCLUSIONS: The results are consistent with findings from previous reviews of interagency collaboration across adult and child services: there were some indications of benefit; and facilitating and inhibiting factors involved working relationships and multi-agency processes, resources and management. The identification of these factors has implications for practitioners, service managers, trainers, commissioners and researchers. PMID- 26860961 TI - Genetic diversity and antimicrobial resistance pattern of Salmonella enterica serovar Enteritidis clinical isolates in Thailand. AB - OBJECTIVE: To trace the history of antimicrobial resistance in Salmonella enterica serovar Enteritidis (S. Enteritidis, SE) circulating in Thailand, we characterised clinical isolates obtained during 2004-2007. METHODS: Antimicrobial resistance profiles, multi-locus variable number tandem repeat analysis (MLVA) types and 3 representative virulence determinants (spvA, sodCI and sopE) were established from SE isolates (n = 192) collected from stool and blood of patients throughout Thailand during the period 2004-2007. RESULTS: Resistance was found in SE against 10 out of 11 antimicrobials studied. The highest resistance ratios were observed for nalidixic acid (83.2%), ciprofloxacin (51.1%) and ampicillin (50.5%), and 25.5% were multidrug resistant. Based on five polymorphic tandem repeat loci analysis, MLVA identified 20 distinct types with three closely related predominant types. A significant increase of AMP resistance from 2004 to 2006 was strongly correlated with that of a MLVA type, 5-5-11-7-3. CONCLUSION: The usage of antimicrobials in human medicine or farm settings might act as selective pressures and cause the spread of resistant strains. Hence, a strict policy on antimicrobial usage needs to be implemented to achieve the control of resistant SE in Thailand. PMID- 26860958 TI - Ubiquitination-mediated degradation of cell cycle-related proteins by F-box proteins. AB - F-box proteins, subunits of SKP1-cullin 1-F-box protein (SCF) type of E3 ubiquitin ligase complexes, have been validated to play a crucial role in governing various cellular processes such as cell cycle, cell proliferation, apoptosis, migration, invasion and metastasis. Recently, a wealth of evidence has emerged that F-box proteins is critically involved in tumorigenesis in part through governing the ubiquitination and subsequent degradation of cell cycle proteins, and dysregulation of this process leads to aberrant cell cycle progression and ultimately, tumorigenesis. Therefore, in this review, we describe the critical role of F-box proteins in the timely regulation of cell cycle. Moreover, we discuss how F-box proteins involve in tumorigenesis via targeting cell cycle-related proteins using biochemistry studies, engineered mouse models, and pathological gene alternations. We conclude that inhibitors of F-box proteins could have promising therapeutic potentials in part through controlling of aberrant cell cycle progression for cancer therapies. PMID- 26860962 TI - Discharge Destination After Total Joint Arthroplasty: An Analysis of Postdischarge Outcomes, Placement Risk Factors, and Recent Trends. AB - BACKGROUND: This study aimed to compare risk of postdischarge adverse events in elective total joint arthroplasty (TJA) patients by discharge destination, identify risk factors for inpatient discharge placement and postdischarge adverse events, and stratify TJA patients based on these risk factors to identify the most appropriate discharge destination. METHODS: Patients who underwent elective primary total hip or knee arthroplasty from 2011 to 2013 were identified in the National Surgical Quality Improvement Program database. Bivariate and multivariate analyses were assessed using perioperative variables. RESULTS: A total of 106,360 TJA patients were analyzed. The most common discharge destinations included home (70%), skilled nursing facility (SNF) (19%), and inpatient rehabilitation facility (IRF; 11%). Bivariate analysis revealed that rates of postdischarge adverse events were higher in SNF and IRF patients (all P <= .001). In multivariate analysis controlling for patient characteristics, comorbidities, and incidence of complication predischarge, SNF and IRF patients were more likely to have postdischarge severe adverse events (SNF: odds ratio [OR]: 1.46, P <= .001; IRF: OR: 1.59, P <= .001) and unplanned readmission (SNF: OR: 1.42, P <= .001; IRF: OR: 1.38, P <= .001). After stratifying patients by strongest independent risk factors (OR: >=1.15, P <= .05) for adverse outcomes after discharge, we found that home discharge is the optimal strategy for minimizing rate of severe 30-day adverse events after discharge (P <= .05 for 5 out of 6 risk levels) and unplanned 30-day readmissions (P <= .05 for 6 out of 7 risk levels). Multivariate analysis revealed incidence of severe adverse events predischarge, female gender, functional status, body mass index >40, smoking, diabetes, pulmonary disease, hypertension, and American Society of Anesthesiologists class 3/4 as independent predictors of nonhome discharge (all P <= .001). CONCLUSION: SNF or IRF discharge increases the risk of postdischarge adverse events compared to home. Modifiable risk factors for nonhome discharge and postdischarge adverse events should be addressed preoperatively to improve patient outcomes across discharge settings. PMID- 26860963 TI - In Reply: "Does Insert Type Affect Clinical and Functional Outcome in Total Knee Arthroplasty?". PMID- 26860964 TI - Does Hip Arthroscopy Affect the Outcomes of a Subsequent Total Hip Arthroplasty? AB - BACKGROUND: Hip arthroscopy utilization is on the rise in the United States. Thus, determining the impact of prior hip arthroscopy on subsequent total hip arthroplasty (THA) is important to understand. METHODS: A retrospective review of a high-volume orthopedic surgery practice's billing database yielded 42 hip arthroscopies that underwent subsequent THA. An age-, sex-, and body mass index (2:1)-matched cohort of primary THAs was used for comparison. RESULTS: No difference was observed in the postoperative Harris Hip Score between groups (92.1 +/- 10.9 vs 90.1 +/- 6.6, P = .20); however, there was greater overall improvement in Harris Hip Score in the control group (40.4 +/- 18.4 vs 45.1 +/- 8.7, P = .05). There were no differences observed in the complication (P = .5) or revision rates (P = .4). CONCLUSION: With the numbers available, prior hip arthroscopy does not appear to have an impact on the functional outcomes of a subsequent THA. PMID- 26860965 TI - An Intact Anterior Cruciate Ligament at the Time of Posterior Cruciate Ligament Retaining Total Knee Arthroplasty Was Associated With Reduced Patient Satisfaction and Inferior Pain and Stair Function. AB - BACKGROUND: Patients with an intact anterior cruciate ligament (ACL) at the time of ACL-sacrificing total knee arthroplasty (TKA) have been suggested to have inferior outcomes compared with those with a dysfunctional ACL. However, to date, no published clinical studies have evaluated the potential link between the condition of the ACL at the time of posterior cruciate ligament-retaining TKA and postoperative pain, function, and satisfaction. As such, the purpose of this study was to compare subjective function, movement-elicited pain, pain at rest, and patient satisfaction between those with an intact or dysfunctional ACL. METHODS: We identified 562 posterior cruciate ligament-retaining TKAs with complete intraoperative and postoperative data. Patients were categorized based on the condition of the ACL at the time of TKA as either being intact or dysfunctional (absent or lax). Knee Society Function Scores, movement-elicited pain, pain at rest, and patient satisfaction were then compared between groups. RESULTS: At mean follow-up of 5.1 years, a significantly lower proportion of patients in the intact group were satisfied with their operation (intact: 391/453 [86.3%] vs dysfunctional: 102/109 [93.6%], P = .0496). Inspection of the individual activities revealed that the groups did not differ in walking ability or pain when walking; however, the intact group reported significantly reduced ability to navigate stairs with greater pain during that activity. CONCLUSION: The lack of difference in pain at rest between groups suggests that pain and functional impairments during more demanding activities such as navigating stairs may be associated with the lost function of the ACL rather than by altered central pain processing. PMID- 26860966 TI - Murine model of large-vein electrolytic injury induction of thrombosis with slow resolution. AB - Deep vein thrombosis (DVT) and its sequela, pulmonary embolism, occur at a rate of 1 per 1000 person/year. Experimental models for evaluation of DVT have many short-comings, such as mechanical occlusion or stenosis to cause thrombosis, rather than the clinical scenario of thrombosis causing occlusion/stenosis. The goal of this study was to develop a model of flow-based large-vein thrombosis with resistance to resolution, to model clinical DVT behavior. Adult male C57Bl/6 mice underwent thrombus induction via an electrolytic injury to the femoral vein (3V positive current for 90s), with subsequent intra-vital fluorescence quantitation of platelet and fibrin accumulation through the first 60 min, and final histomorphometric volume evaluation at 1, 7, 14, and 28 days. Platelet accumulation at the injury site was comparable to a milder electrolytic injury, whereas fibrin was greatly augmented by 60 min in the more severe injury model. Thrombi showed persistent presence at 1 and 7 days, with remodeling to a stenotic fibrosis that encroached into the lumen at 14 and 28 days. The thrombotic/fibrotic volume within the femoral vein fell by 23% from 1 to 7 days, but had a residual presence at 28 days that was 31% the 1-day volume. This new model may provide an alternative approach to evaluating DVT persistence and therapeutic inhibition, to develop a better understanding of the clinical progression of DVT to thrombophlebitis. PMID- 26860967 TI - Silicene nanomeshes: bandgap opening by bond symmetry breaking and uniaxial strain. AB - Based on the first-principles calculations, we have investigated in detail the bandgap opening of silicene nanomeshes. Different to the mechanism of bandgap opening induced by the sublattice equivalence breaking, the method of degenerate perturbation through breaking the bond symmetry could split the pi-like bands in the inversion symmetry preserved silicene nanomeshes, resulting into the pia1 - pia2 and piz1 - piz2 band sets with sizable energy intervals. Besides the bandgap opening in the nanomeshes with Dirac point being folded to Gamma point, the split energy intervals are however apart away from Fermi level to leave the semimetal nature unchanged for the other nanomeshes with Dirac points located at opposite sides of Gamma point as opposite pseudo spin wave valleys. A mass bandgap could be then opened at the aid of uniaxial strain to transfer the nanomesh to be semiconducting, whose width could be continuously enlarged until reaching its maximum Emax. Moreover, the Emax could also be tuned by controlling the defect density in silicene nanomeshes. These studies could contribute to the understanding of the bandgap engineering of silicene-based nanomaterials to call for further investigations on both theory and experiment. PMID- 26860968 TI - Linezolid and dexamethasone experience in a serious case of listeria rhombencephalitis. AB - Listeria rhombencephalitis is a rare cause of brain stem encephalitis. We report a case with a history of immunosupressive therapy due to Takayasu's arteritis that was treated with corticosteroids and linezolid for Listeria rhombencephalitis. A 63-year-old woman was admitted to the hospital with fever, headache, nausea, and vomiting. The patient's body temperature was 38 degrees C, and she had a stiff neck. Listeria monocytogenes was isolated from the cerebrospinal fluid (CSF), and penicillin G and gentamicin treatment was initiated. Linezolid and dexamethasone were added. Due to hematuria and thrombocytopenia, the linezolid was discontinued. In immunocompromised patients with CNS infections, Listeria rhombencephalitis should be suspected. Linezolid can be used in combination with dexamethasone. PMID- 26860969 TI - Transthoracic Echocardiography Provides Important Long-Term Prognostic Information in Selected Patients Undergoing Endovascular Abdominal Aortic Repair. AB - BACKGROUND: The value of performing transthoracic echocardiography (TTE) as part of the clinical assessment of patients awaiting endovascular repair of the abdominal aorta is little evaluated. We aimed to estimate the prognostic importance of information derived from TTE on long-term all-cause mortality in a selected group of patients undergoing endovascular aneurysm repair. METHODS AND RESULTS: This was a retrospective cohort study of 273 consecutive patients selected for endovascular aneurysm repair. All patients included in the analysis underwent TTE before their procedure. Multivariable Cox regression analysis was used to estimate the effect of TTE measures on all-cause mortality. Over a mean follow-up of 3.2+/-1.5 years, there were 78 deaths with a mean time to death of 1.28+/-1.16 years. A greater tubular ascending aorta (hazard ratio [HR] 5.6, 95% confidence interval [CI] 2.77-11.33), presence of mitral regurgitation (HR 8.13, 95% CI 4.09-12.16), lower left ventricular ejection fraction (HR 0.96, 95% CI 0.93-0.98), younger age (HR 0.97, 95% CI 0.95-0.99), and presence of diabetes mellitus (HR 1.46, 95% CI 1.24-1.89) were predictors of all-cause mortality. CONCLUSIONS: Echocardiography provides important long-term prognostic information in patients undergoing endovascular aneurysm repair. These TTE indices were more important at predicting outcome than standard conventional risk factors in this patient group. A greater tubular ascending aorta, presence of mitral regurgitation, reduced left ventricular ejection fraction, younger age, and diabetes mellitus were independently associated with long-term mortality. PMID- 26860970 TI - Sex- and Method-Specific Reference Values for Right Ventricular Strain by 2 Dimensional Speckle-Tracking Echocardiography. AB - BACKGROUND: Despite the fact that assessment of right ventricular longitudinal strain (RVLS) carries important implications for patient diagnosis, prognosis, and treatment, its implementation in clinical settings has been hampered by the limited reference values and the lack of uniformity in software, method, and definition used for measuring RVLS. Accordingly, this study was designed to establish (1) the reference values for RVLS by 2-dimensional speckle-tracking echocardiography; and (2) their relationship with demographic, hemodynamic, and cardiac factors. METHODS AND RESULTS: In 276 healthy volunteers (55% women; age, 18-76 years), free wall and septum RVLS (6 segments) and free wall RVLS (3 segments) using both 6- and 3-segment regions of interest were obtained. Feasibility of 6-segment RVLS was 92%. Free wall RVLS from 3- versus 6-segment regions of interest had similar values, yet 6-segment region of interest was more feasible (86% versus 73%; P<0.001) and reproducible. Reference values (lower limits of normality) were as follows: 6-segment RVLS, -24.7+/-2.6% (-20.0%) for men and -26.7+/-3.1% (-20.3%) for women; 3-segment RVLS, -29.3+/-3.4% (-22.5%) for men and -31.6+/-4.0% (-23.3%) for women (P<0.001). Free wall RVLS was 5+/-2 strain units (%) larger in magnitude than 6-segment RVLS, 10+/-4% larger than septal RVLS, and 2+/-4% larger in women than in men (P<0.001). At multivariable analysis, age, sex, pulmonary systolic pressure, right atrial minimal volume, as well as right atrial and left ventricular longitudinal strain resulted as correlates of RVLS values. CONCLUSIONS: This is the largest study providing sex- and method-specific reference values for RVLS. Our data may foster the implementation of 2-dimensional speckle-tracking echocardiography-derived RV analysis in clinical practice. PMID- 26860971 TI - Preoperative Transthoracic Echocardiography in Abdominal Aortic Aneurysm: A New Thermometer. PMID- 26860972 TI - Protective Effect of Gomisin N against Endoplasmic Reticulum Stress-Induced Hepatic Steatosis. AB - Gomisin N is a physiological substance derived from Schisandra chinensis. In the present study, the in vitro and in vivo effects of gomisin N on endoplasmic reticulum (ER) stress and hepatic steatosis were investigated. We quantified the expression of markers of ER stress, including glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein (C/EBP) homolog protein (CHOP), and X-box binding protein-1 (XBP-1), and triglyceride (TG) accumulation, in HepG2 cells treated with tunicamycin or palmitate. Tunicamycin treatment in HepG2 cells induced expression of markers of ER stress and increased TG levels; Gomisin N reversed these effects, reducing the expression of markers of ER stress and TG levels. Similar effects were seen following palmitate pretreatment of HepG2 cells. The inhibitory effects of gomisin N were further confirmed in mice injected with tunicamycin. Gomisin N reduced expression of markers of ER stress and decreased TG levels in mouse liver after tunicamycin injection. Furthermore, gomisin N decreased expression of inflammatory and lipogenic genes in palmitate incubated HepG2 cells. These results suggest that gomisin N inhibits ER stress and ameliorates hepatic steatosis induced by ER stress. PMID- 26860976 TI - Case report: malaria attack in southern Brazil - five-decade relapse, simian malaria or something else? PMID- 26860973 TI - A herbal formula comprising Rosae Multiflorae Fructus and Lonicerae Japonicae Flos, attenuates collagen-induced arthritis and inhibits TLR4 signalling in rats. AB - RL, a traditional remedy for Rheumatoid arthritis (RA), comprises two edible herbs, Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. We have reported that RL could inhibit the production of inflammatory mediators in immune cells. Here we investigated the effects and the mechanism of action of RL in collagen induced arthritis (CIA) rats. RL significantly increased food intake and weight gain of CIA rats without any observable adverse effect; ameliorated joint erythema and swelling; inhibited immune cell infiltration, bone erosion and osteophyte formation in joints; reduced joint protein expression levels of TLR4, phospho-TAK1, phospho-NF-kappaB p65, phospho-c-Jun and phospho-IRF3; lowered levels of inflammatory factors (TNF-alpha, IL-6, IL-1beta, IL-17A and MCP-1 in sera and TNF-alpha, IL-6, IL-1beta and IL-17A in joints); elevated serum IL-10 level; reinvigorated activities of antioxidant SOD, CAT and GSH-Px in the liver and serum; reduced Th17 cell proportions in splenocytes; inhibited splenocyte proliferation and activation; and lowered serum IgG level. In conclusion, RL at nontoxic doses inhibited TLR4 signaling and potently improved clinical conditions of CIA rats. These findings provide further pharmacological justifications for the traditional use of RL in RA management. PMID- 26860977 TI - WHO reform: bring back GOARN and Task Force 'Scorpio'. PMID- 26860974 TI - AP-1 transcription factor mediates VEGF-induced endothelial cell migration and proliferation. AB - VEGF, upon binding to its endothelial cell specific receptors VEGF-R1 and VEGF R2, can induce endothelial cell migration, proliferation and angiogenesis. However, the molecular mechanism of these effects still remains unclear. In this study, we investigated whether VEGF promotes human umbilical vascular endothelial cell (HUVEC) migration and proliferation through activator protein-1 transcription factor (AP-1) family. We first showed that VEGF induces immediate early genes AP-1 family gene expression differentially with the profound induction of JunB (both mRNA and protein) under various conditions (PBS, DMSO or control adenoviruses). The increase in AP-1 mRNA expression occurs primarily at the transcriptional level. Inhibition of AP-1 DNA binding activity by adenovirus expressing a potent dominant negative form of c-Fos (Afos) significantly attenuated VEGF-induced HUVEC migration and proliferation and cyclin D1 expression. Knockdown of JunB with adenovirus expressing JunB shRNA reduces VEGF induced JunB expression and attenuated HUVEC migration. However the shJunB expressing virus has no effect on VEGF-induced cyclin D1 protein expression and proliferation. These results suggest that VEGF-induced endothelial migration is mediated primarily by induction of JunB whereas the promotion of endothelial proliferation by VEGF is mediated by JunB-independent AP-1 family members. PMID- 26860978 TI - Evaluation of flow cytometric HIT assays in relation to an IgG-Specific immunoassay and clinical outcome. AB - BACKGROUND: Heparin-induced thrombocytopenia (HIT) is a severe side effect of heparin treatment caused by platelet activating IgG antibodies generated against the platelet factor 4 (PF4)-heparin complex. Thrombocytopenia and thrombosis are the leading clinical symptoms of HIT. METHODS: The clinical pretest probability of HIT was evaluated by the 4T score system. Laboratory testing of HIT was performed by immunological detection of antibodies against PF4-heparin complex (EIA) and two functional assays. Heparin-dependent activation of donor platelets by patient plasma was detected by flow cytometry. Increased binding of Annexin-V to platelets and elevated number of platelet-derived microparticles (PMP) were the indicators of platelet activation. RESULTS: EIA for IgG isotype HIT antibodies was performed in 405 suspected HIT patients. Based on negative EIA results, HIT was excluded in 365 (90%) of cases. In 40 patients with positive EIA test result functional tests were performed. Platelet activating antibodies were detected in 17 cases by Annexin V binding. PMP count analysis provided nearly identical results. The probability of a positive flow cytometric assay result was higher in patients with elevated antibody titer. 71% of patients with positive EIA and functional assay had thrombosis. CONCLUSIONS: EIA is an important first line laboratory test in the diagnosis of HIT; however, HIT must be confirmed by a functional test. Annexin V binding and PMP assays using flow cytometry are functional HIT tests convenient in a clinical diagnostic laboratory. The positive results of functional assays may predict the onset of thrombosis. (c) 2016 International Clinical Cytometry Society. PMID- 26860979 TI - Boosting the Transparency of Thin Layers by Coatings of Opposing Susceptibility: How Metals Help See Through Dielectrics. AB - We propose a hypothesis that a very thin layer can be made more transparent by adding a thin coating with susceptibility of opposing sign. Two experimental tests backed by a theoretical model support this hypothesis. First, we show that the visible and near-infrared transmission through a semi-transparent silver film can be enhanced by up to ~70% and spectrally tailored depending on the type and thickness of the dielectric coating. Material types explored as dielectric coating layers include conventional metal oxides (titanium dioxide) and lesser explored elemental semiconductors (undoped silicon, p-type silicon, and germanium). Second, and more surprisingly, we show that coating a 50-nm-thick silicon nitride membrane with a 10-nm-thick silver layer can modestly enhance the transmission by up to 6 +/- 1% in the blue part of the spectrum. Transmission enhancements are observed for three silver-coated membranes in different configurations. Thinner silver coatings are theoretically capable of enhancement factors greater than 10%, but implementation is restricted by challenges in making smooth and continuous silver films below 10 nm in thickness. This study is important because it is the first demonstration of reciprocity with respect to the transmission enhancements achieved by combining thin metallic and dielectric layers. PMID- 26860980 TI - Impact of different cell penetrating peptides on the efficacy of antisense therapeutics for targeting intracellular pathogens. AB - There is a pressing need for novel and innovative therapeutic strategies to address infections caused by intracellular pathogens. Peptide nucleic acids (PNAs) present a novel method to target intracellular pathogens due to their unique mechanism of action and their ability to be conjugated to cell penetrating peptides (CPP) to overcome challenging delivery barriers. In this study, we targeted the RNA polymerase alpha subunit (rpoA) using a PNA that was covalently conjugated to five different CPPs. Changing the conjugated CPP resulted in a pronounced improvement in the antibacterial activity observed against Listeria monocytogenes in vitro, in cell culture, and in a Caenorhabditis elegans (C. elegans) infection model. Additionally, a time-kill assay revealed three conjugated CPPs rapidly kill Listeria within 20 minutes without disrupting the bacterial cell membrane. Moreover, rpoA gene silencing resulted in suppression of its message as well as reduced expression of other critical virulence genes (Listeriolysin O, and two phospholipases plcA and plcB) in a concentration dependent manner. Furthermore, PNA-inhibition of bacterial protein synthesis was selective and did not adversely affect mitochondrial protein synthesis. This study provides a foundation for improving and developing PNAs conjugated to CPPs to better target intracellular pathogens. PMID- 26860982 TI - Determination of Scrub typhus Suggests a New Epidemic Focus in the Anhui Province of China. AB - In 2007, 19 cases of a scrub typhus epidemic occurred within a week at a sports school in Mingguang County, Anhui Province, where no previous incidence of this mite borne disease had been reported. Sero-surveillance in 2009 indicated that 10 of the 100 school students possessed anti-Orientia tsutsugamushi antibodies. From 2009 to 2013, 60 small animals and 2250 mites were collected in the vicinity of the school. 5 of the Apodemus agrarius samples and 1 group of Leptotrombidium linhuaikongense tested positive via PCR for O. tsutsugamushi. Two strains of O. tsutsugamushi were identified by injecting Kun Ming (KM) mice peritoneally with the organs of either Apodemus agrarius or Leptotrombidium linhuaikongense. Apart from sharing 98% homology with the O. tsutsugamushi Yongworl strain, genes encoding the membrane protein from the two O. tsutsugamushi isolates shared >99% sequence homology with each other, reflecting the consistency of the pathogen in both the vector and the host. In addition, we also characterized a chronic scrub typhus infection in a local patient. The membrane protein gene fragment from the patient's blood shared 99% homology with O. tsutsugamushi Gilliam strain, suggesting that more than one O. tsutsugamushi strain is present at this location. PMID- 26860981 TI - Rescue of a Mouse Model of Spinal Muscular Atrophy With Respiratory Distress Type 1 by AAV9-IGHMBP2 Is Dose Dependent. AB - Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an autosomal recessive disease occurring during childhood. The gene responsible for disease development is a ubiquitously expressed protein, IGHMBP2. Mutations in IGHMBP2 result in the loss of alpha-motor neurons leading to muscle atrophy in the distal limbs accompanied by respiratory complications. Although genetically and clinically distinct, proximal SMA is also caused by the loss of a ubiquitously expressed gene (SMN). Significant preclinical success has been achieved in proximal SMA using viral-based gene replacement strategies. We leveraged the technologies employed in SMA to demonstrate gene replacement efficacy in an SMARD1 animal model. Intracerebroventricular (ICV) injection of single-stranded AAV9 expressing the full-length cDNA of IGHMBP2 in a low dose led to a significant level of rescue in treated SMARD1 animals. Consistent with drastically increased survival, weight gain, and strength, the rescued animals demonstrated a significant improvement in muscle, NMJ, motor neurons, and axonal pathology. In addition, increased levels of IGHMBP2 in lumbar motor neurons verified the efficacy of the virus to transduce the target tissues. Our results indicate that AAV9-based gene replacement is a viable strategy for SMARD1, although dosing effects and potential negative impacts of high dose and ICV injection should be thoroughly investigated. PMID- 26860984 TI - Targeting the ERK signaling pathway as a potential treatment for insulin resistance and type 2 diabetes. AB - Extracellular signal-regulated kinase (ERK) has been implicated in the development of insulin resistance associated with obesity and type 2 diabetes mellitus. We have now examined the potential of pharmacological targeting of the ERK pathway with MEK (ERK kinase) inhibitors (PD184352 and PD0325901) for the treatment of obesity-associated insulin resistance. The effects of PD184352 and PD0325901 on the expression of adipocytokines and lipolysis activity were thus examined in 3T3-L1 adipocytes maintained in long-term culture as a model of adipocyte hypertrophy. Leptin receptor-deficient (db/db) mice and high-fat diet fed KKAy mice, both of which are models of type 2 diabetes, were also treated orally with PD184352 to examine its effects on the diabetic condition. ERK activity was increased in hypertrophic 3T3-L1 adipocytes as well as in adipose tissue of db/db mice and high-fat diet-fed KKAy mice, and this enhanced ERK signaling was associated with dysregulation of adipocytokine expression and increased lipolysis activity. Specific blockade of the ERK pathway in hypertrophic 3T3-L1 adipocytes by MEK inhibitors ameliorated the dysregulation of adipocytokine expression and suppressed the enhanced lipolysis activity. Furthermore, repeated oral administration of PD184352 normalized hyperglycemia and hyperlipidemia and improved insulin sensitivity and glucose tolerance in the diabetic mice. These results suggest that sustained activation of the ERK pathway in adipocytes is associated with the pathogenesis of type 2 diabetes and that selective blockade of this pathway with MEK inhibitors warrants further study as a promising approach to the treatment of insulin resistance and type 2 diabetes. PMID- 26860983 TI - The peroxisome proliferator-activated receptors under epigenetic control in placental metabolism and fetal development. AB - The placental metabolism can adapt to the environment throughout pregnancy to both the demands of the fetus and the signals from the mother. Such adaption processes include epigenetic mechanisms, which alter gene expression and may influence the offspring's health. These mechanisms are linked to the diversity of prenatal environmental exposures, including maternal under- or overnutrition or gestational diabetes. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that contribute to the developmental plasticity of the placenta by regulating lipid and glucose metabolism pathways, including lipogenesis, steroidogenesis, glucose transporters, and placental signaling pathways, thus representing a link between energy metabolism and reproduction. Among the PPAR isoforms, PPARgamma appears to be the main modulator of mammalian placentation. Certain fatty acids and lipid-derived moieties are the natural activating PPAR ligands. By controlling the amounts of maternal nutrients that go across to the fetus, the PPARs play an important regulatory role in placenta metabolism, thereby adapting to the maternal nutritional status. As demonstrated in animal studies, maternal nutrition during gestation can exert long-term influences on the PPAR methylation pattern in offspring organs. This review underlines the current state of knowledge on the relationship between environmental factors and the epigenetic regulation of the PPARs in placenta metabolism and offspring development. PMID- 26860986 TI - High-resolution manometric subtypes as a predictive factor for the treatment of achalasia: A meta-analysis and systematic review. AB - OBJECTIVE: To assess manometric subtypes as predictive factors for the treatment efficacies of pneumatic balloon dilatation (PBD) and laparoscopic Heller myotomy (LHM) in patients with achalasia. METHODS: A systematic search of the Pubmed, Embase and Cochrane Library database was conducted to identify relevant publications on high-resolution manometric subtypes and different therapies for achalasia with predefined inclusion and exclusion criteria. Data on the success rates after PBD or LHM for different manometric subtypes were extracted. The pooled odds ratio (OR) and 95% confidence interval (CI) for different manometric subtypes were estimated using STATA 13.0. RESULTS: In all, nine studies met the inclusion criteria. A total of 298 patients having achalasia receiving PBD and 429 undergoing LHM were included in the meta-analysis. The pooled OR between the subtypes of achalasia after PBD or LHM showed that the best and worse treatment outcomes were found in patients with type II and III achalasia, respectively (type I vs type II after PBD: OR 0.16, 95% CI 0.08-0.36, P = 0.000; type I vs type III after PBD: OR 3.64, 95% CI 1.55-8.53, P = 0.003; type II vs type III after PBD: OR 27.18, 95% CI 9.08-81.35, P = 0.000; type I vs type II after LHM: OR 0.26, 95% CI 0.12-0.56, P = 0.001; type I vs type III after LHM: OR 1.89, 95% CI 0.80-4.50, P = 0.148; type II vs type III after LHM: OR 6.86, 95% CI 2.72 17.28, P = 0.000). CONCLUSION: Type II achalasia shows the best prognosis after PBD and LHM, while type III achalasia has the worst prognosis. PMID- 26860985 TI - Ribosome biogenesis may augment resistance training-induced myofiber hypertrophy and is required for myotube growth in vitro. AB - Resistance exercise training (RT) is the most effective method for increasing skeletal muscle mass in older adults; however, the amount of RT-induced muscle growth is highly variable between individuals. Recent evidence from our laboratory and others suggests ribosome biogenesis may be an important factor regulating RT-induced hypertrophy, and we hypothesized that the extent of hypertrophy is at least partly regulated by the amount of RT-induced ribosome biogenesis. To examine this, 42 older adults underwent 4 wk of RT aimed at inducing hypertrophy of the knee extensors (e.g., 2 sets of squat, leg press, and knee extension, 10-12 repetition maximums, 3 days/wk), and vastus lateralis muscle biopsies were performed pre- and post-RT. Post hoc K-means cluster analysis revealed distinct differences in type II myofiber hypertrophy among subjects. The percent change in type II myofiber size in nonresponders (Non; n = 17) was -7%, moderate responders (Mod; n = 19) +22%, and extreme responders (Xtr; n = 6) +83%. Total muscle RNA increased only in Mod (+9%, P < 0.08) and Xtr (+26%, P < 0.01), and only Xtr increased rRNA content (+40%, P < 0.05) and myonuclei/type II fiber (+32%, P < 0.01). Additionally, Mod and Xtr had a greater increase in c-Myc protein levels compared with Non (e.g., approximately +350 and +250% vs. +50%, respectively, P < 0.05). In vitro studies showed that growth factor-induced human myotube hypertrophy is abolished when rRNA synthesis is knocked down using the Pol I-specific inhibitor CX-5461. Overall, these data implicate ribosome biogenesis as a key process regulating the extent of RT induced myofiber hypertrophy in older adults. PMID- 26860987 TI - Extensive molluscum contagiosum virus infection in a young adult receiving fingolimod. AB - Fingolimod-related viral infections have been described on several occasions since its introduction in 2010. We hereby add a report on an otherwise immunocompetent, 18-year old Caucasian man with relapsing-remitting multiple sclerosis who developed a protracted and extensive molluscum contagiosum (MC) virus infection shortly after being started on fingolimod. Wide-spread cutaneous MC infections in adult patients are considered indicative of underlying immunosuppression. Neurologists prescribing fingolimod ought to be aware of a possibly increased risk of MC, but also need to know about its relative benignity, lack of extra-cutaneous complications, and adequate treatment options. PMID- 26860988 TI - Early stage squamous cell carcinoma of the lower lip: predictive factors for recurrence. AB - OBJECTIVE: This study aimed to evaluate the effect of tumour thickness on other clinicopathological parameters in early stage lower lip squamous cell carcinoma. METHODS: Forty-six consecutive patients with lower lip squamous cell carcinoma were included in the study. Demographic, clinical and pathological data were retrospectively collected. RESULTS: The mean follow-up period for all patients was 32.0 +/- 18.9 months. Forty-four tumours were staged as T1 and two were T2. Twelve patients underwent neck dissection. Two patients presented with neck metastasis in the follow-up period. Four patients (8.7 per cent) had local recurrence. Correlation analysis revealed a significant relationship between microscopic tumour thickness and local tumour recurrence (r = 0.328, p = 0.045). CONCLUSION: Surgical margin control is important to prevent local recurrence, especially in thicker tumours. In addition, neck metastasis is rare in early stage lower lip squamous cell carcinoma. A 'wait and see' policy might be preferred in early stage T1 lower lip squamous cell carcinoma cases. PMID- 26860990 TI - Morphological analysis and preoperative simulation of a double-chambered right ventricle using 3-dimensional printing technology. AB - We present a case of a double-chambered right ventricle in adulthood, in which we tried a detailed morphological assessment and preoperative simulation using 3 dimensional (3D) heart models for improved surgical planning. Polygonal object data for the heart were constructed from computed tomography images of this patient, and transferred to a desktop 3D printer to print out models in actual size. Medical staff completed all of the work processes. Because the 3D heart models were examined by hand, observed from various viewpoints and measured by callipers with ease, we were able to create an image of the complete form of the heart. The anatomical structure of an anomalous bundle was clearly observed, and surgical approaches to the lesion were simulated accurately. During surgery, we used an incision on the pulmonary infundibulum and resected three muscular components of the stenosis. The similarity between the models and the actual heart was excellent. As a result, the operation for this rare defect was performed safely and successfully. We concluded that the custom-made model was useful for morphological analysis and preoperative simulation. PMID- 26860989 TI - Leukemia and chromosomal instability in aged Fancc-/- mice. AB - Fanconi anemia (FA) is an inherited disorder of genomic instability associated with high risk of myelodysplasia and acute myeloid leukemia (AML). Young mice deficient in FA core complex genes do not naturally develop cancer, hampering preclinical studies on malignant hematopoiesis in FA. Here we describe that aging Fancc(-/-) mice are prone to genomically unstable AML and other hematologic neoplasms. We report that aneuploidy precedes malignant transformation during Fancc(-/-) hematopoiesis. Our observations reveal that Fancc(-/-) mice develop hematopoietic chromosomal instability followed by leukemia in an age-dependent manner, recapitulating the clinical phenotype of human FA and providing a proof of concept for future development of preclinical models of FA-associated leukemogenesis. PMID- 26860991 TI - Outcome measures in older persons with acquired joint contractures: a systematic review and content analysis using the ICF (International Classification of Functioning, Disability and Health) as a reference. AB - BACKGROUND: Joint contractures are a common health problem in older persons with significant impact on activities of daily living. We aimed to retrieve outcome measures applied in studies on older persons with joint contractures and to identify and categorise the concepts contained in these outcome measures using the ICF (International Classification of Functioning, Disability and Health) as a reference. METHODS: Electronic searches of Medline, EMBASE, CINAHL, Pedro and the Cochrane Library were conducted (1/2002-8/2012). We included studies in the geriatric rehabilitation and nursing home settings with participants aged >= 65 years and with acquired joint contractures. Two independent reviewers extracted the outcome measures and transferred them to concepts using predefined conceptual frameworks. Concepts were subsequently linked to the ICF categories. RESULTS: From the 1057 abstracts retrieved, 60 studies met the inclusion criteria. We identified 52 single outcome measures and 24 standardised assessment instruments. A total of 1353 concepts were revealed from the outcome measures; 96.2% could be linked to 50 ICF categories in the 2nd level; 3.8% were not categorised. Fourteen of the 50 categories (28%) belonged to the component Body Functions, 4 (8%) to the component Body Structures, 26 (52%) to the component Activities and Participation, and 6 (12%) to the component Environmental Factors. CONCLUSIONS: The ICF is a valuable reference for identifying and quantifying the concepts of outcome measures on joint contractures in older people. The revealed ICF categories remain to be validated in populations with joint contractures in terms of clinical relevance and personal impact. PMID- 26860992 TI - A discrete choice experiment studying students' preferences for scholarships to private medical schools in Japan. AB - BACKGROUND: The shortage of physicians in rural areas and in some specialties is a societal problem in Japan. Expensive tuition in private medical schools limits access to them particularly for students from middle- and low-income families. One way to reduce this barrier and lessen maldistribution is to offer conditional scholarships to private medical schools. METHODS: A discrete choice experiment is carried out on a total of 374 students considering application to medical schools. The willingness to receive a conditional scholarship program to private medical schools is analyzed. RESULTS: The probability of attending private medical schools significantly decreased because of high tuition, a postgraduate obligation to provide a service in specific specialty areas, and the length of time of this obligation. An obligation to provide a service in rural regions had no significant effect on this probability. To motivate non-applicants to private medical schools to enroll in such schools, a decrease in tuition to around 1.2 million yen (US$ 12,000) or less, which is twice that of public schools, was found to be necessary. Further, it was found that non-applicants to private medical schools choose to apply to such schools even with restrictions if they have tuition support at the public school level. CONCLUSIONS: Conditional scholarships for private medical schools may widen access to medical education and simultaneously provide incentives to work in insufficiently served areas. PMID- 26860994 TI - Sixty seconds on . . . the Cancer Drugs Fund. PMID- 26860993 TI - Successful external validation of a model to predict other cause mortality in localized prostate cancer. AB - BACKGROUND: Although life expectancy estimation is vital to decision making for localized prostate cancer, there are few, if any, valid and usable tools. Our goal was to create and validate a prediction model for other cause mortality in localized prostate cancer patients that could aid clinician's initial treatment decisions at the point of care. METHODS: We combined an adjusted Social Security Administration table with a subset of comorbidities from a UK actuarial life expectancy model. Life tables were adjusted on the basis of survival data from a cohort of almost 10,000 radical prostatectomy patients treated at four major US academic institutions. Comorbidity-specific odds ratios were calculated and incorporated with baseline risk of mortality. We externally validated the model on 2898 patients from the Prostate Cancer Outcomes Study, which included men diagnosed with prostate cancer in six SEER cancer registries. These men had sufficient follow-up for our endpoints of 10- and 15-year mortality and also had self-reported comorbidity data. RESULTS: Life expectancy for prostate cancer patients were close to that of a typical US man who was 3 years younger. On external validation, 10- and 15-year concordance indexes were 0.724 and 0.726, respectively. Our model exhibited excellent calibration. Taking into account differences between how comorbidities are used in the model versus how they were recorded in the validation cohort, calibration would improve for most patients, but there would be overestimation of the risk of death in the oldest and sickest patients. CONCLUSIONS: We successfully created and externally validated a new life expectancy prediction model that, while imperfect, has clear advantages to any alternative. We urge consideration of its use in counseling patients with localized prostate cancer. PMID- 26860996 TI - In Silico Studies Most Employed in the Discovery of New Antimicrobial Agents. AB - The present review summarizes the methods most used in drug search and design, which may help to keep pace with the growing antibiotic resistance among pathogens. The rate of reduction in the effectiveness of many antimicrobial medications, caused by this resistance, is faster than new drug development, thereby creating a worldwide public health threat. Among the scientific community, the urgency of finding new drugs is peaking interest in the use of in silico studies to explore the interaction of compounds with target receptors. With this approach, small molecules (designed or retrieved from data bases) are tested with computer-aided molecular simulation to explore their efficacy. That is, ligand-protein complexes are constructed and evaluated via virtual screening (VS), molecular dynamics (MD), and docking simulations with the data from the physical, chemical and pharmacological properties of such molecules. Additionally, the application of quantitative structure-activity relationship (QSAR), multi-target quantitative structure-activity relationship (mt- QSAR), and multi-tasking quantitative structure-biological effect (mtk-QSBER) can be enhanced by principal component analysis and systematic workflows. These types of studies aid in selecting a group of promising molecules with high potency and selectivity as well as low toxicity, thus making in vitro and in vivo (animal model) testing more efficient. Since knowledge of the receptor topography and receptor-ligand interactions has yielded promising compounds and effective drugs, there is now no doubt that the use of in silico tools can lead to more rapid validation of new potential drugs for preclinical studies and clinical trials. PMID- 26860995 TI - Predictors of residential stability among homeless young adults: a cohort study. AB - BACKGROUND: Homelessness episodes have been shown to be associated with serious health outcomes among youth. This study was undertaken to estimate the probability of reaching residential stability over time and to identify predictors of residential stability among homeless young adults aged 18 to 25 years. METHODS: A prospective cohort study was carried out in Montreal, Canada, between April 5(th) 2006 and January 21(th) 2009. Interviews conducted every three months included questions on life conditions and social and mental health factors that are known to influence residential trajectories. Residential status was determined, starting on the first day after recruitment; each follow-up day was classified as a homeless day or a housed day. A period of 90 days was used to define residential stability; therefore the main study outcome was the occurrence of the first consecutive 90 housed days during the follow-up period. Kaplan-Meier and Cox proportional-hazards regression analyses were conducted. RESULTS: Of the 359 participants, 284 reached 90 days of residential stability over the study period, representing an annual probability of 80.5 %. In multivariate analysis, youth who had a high school degree, had a formal sector activity, and those who had sought psychological help were more likely to reach residential stability. Being a man, injecting substances, and having an informal sector activity were associated with a decreased probability to reach residential stability. CONCLUSION: Exposure to factors related to opportunities that promote social integration increases the chance of reaching residential stability. On the other hand, factors related to high level of street entrenchment seem to interfere with stabilization. Maximum efforts should be made to prevent chronic homelessness among youth, targeting not only individual impairments but also hinging on services adapted to foster social connections among the youth. PMID- 26860997 TI - Role of Nanotechnology for Enzyme Replacement Therapy in Lysosomal Diseases. A Focus on Gaucher's Disease. AB - Lysosomal storage diseases (LSDs) comprise a group of rare inherited chronic syndromes that cause deficiency of specific native enzymes within the lysosomes. The macromolecular compounds that are usually catabolized by lysosomal enzymes are accumulated within these organelles, causing progressive damage to tissues, skeleton and organs and, in several cases, the central nervous system (CNS). The damage caused by substrate accumulation finally results in physical deterioration, functional impairment and potential death. Up to date, the most promising therapy for most LSDs is enzyme-replacement therapy (ERT), which provides patients with the corresponding active enzyme. However, these enzymes do not have enough stability in blood, the treatment must be therefore periodically administrated by i.v. infusion under medical supervision, and immunogenicity issues are frequent. In addition, affected areas within the CNS, where the blood brain barrier (BBB) is a major obstacle, cannot be reached by the enzymes. Nanotechnology can provide useful carriers to successfully protect and preserve enzymes, and transport them through the BBB towards brain locations. Several strategies based on targeting specific receptors on the BBB have led to nanoparticles that successfully carry sensitive molecules to the brain. Then, the main LSDs are described and a thorough review of nanotechnology strategies for brain delivery studied up to date is presented. PMID- 26860998 TI - Anti-Angiogenic Therapy: Strategies to Develop Potent VEGFR-2 Tyrosine Kinase Inhibitors and Future Prospect. AB - Tumor angiogenesis has always been a major gap for effective cancer therapy. Interruption of aberrant angiogenesis by specific inhibitors targeting receptor tyrosine kinases (RTKs) has been of great interests to medicinal chemists. Among the factors that are involved in tumor angiogenesis, vascular endothelial growth factor receptor-2 (VEGFR-2) is validated as the most closely related factor which can drive angiogenesis through binding with its natural ligand VEGF. The well validated VEGF-driven VEGFR-2 signaling pathway can stimulate many endothelial responses, including increasing vessel permeability and enhancing endothelial cell proliferation, migration and differentiation. Consequently, circumventing angiogenesis by VEGFR-2 inhibitors represents a promising strategy for counteracting various VEGFR-2-mediated disorders as well as drug resistance. Over the past decades, a considerable number of novel small molecular VEGFR-2 inhibitors have been exploited with diverse chemical scaffolds. Especially, recent frequently launched inhibitors have declared their research values and therapeutic potentials in oncology. Still, the antiangiogenesis based treatment remains an ongoing challenge. In this review, a comprehensive retrospective of newly emerged VEGFR-2 inhibitors have been summarized, with the emphasis on the structure-activity relationship (SAR) investigation, and also binding patterns of representative inhibitors with biotargets. On the basis of all of this information, varied strategies for developing potent VEGFR-2 inhibitors and the future prospect of the clinical application of antiangiogenic inhibitors are discussed hereby. PMID- 26860999 TI - Evaluation of Novel Biomarkers of Acute Kidney Injury: The Possibilities and Limitations. AB - Despite the recent findings concerning pathogenesis and novel therapeutic strategies, the mortality rate in patients with acute kidney injury (AKI) remains very high. Early detection of patients with impaired renal function may help to ensure more aggresive treatment and to improve clinical outcome. Serum creatinine is still gold standard of kidney injury, although it is well known as an insensitive and unreliable biomarker (for example, its concentration does not increase significantly until about half of the kidney function is lost). Considering these data, researches and clinicians are making great efforts in the past decade in order to discover and validate novel AKI biomarkers. Kidney injury molecule-1 (KIM-1), Neutrophil gelatinase-associated lipocalin (NGAL), Interleukin-18 (IL-18), Cystatin C (Cys-C) are some of new, promising markers of kidney damage which are currently in the focus of preclinical and clinical studies. Recent data suggest that some of these new biomarkers represent important parametars of acute tubular necrosis (ATN) and reliable predictors of development and prognosis of AKI. Beside that, monitoring of these markers could have significant importance for early diagnosis and clinical course, not only in patients with various forms of AKI and other renal diseases, but also in patients with cardiorenal syndrome, heart failure, cardiopulmonary bypass, cardiothoracical surgical interventions, in the pediatric emergency setting etc. The aim of this review is to summarize the literature data concerning some new biomarkers, evaluate their role as well as their limitations in the early diagnosis and predict clinical outcome of some renal diseases. PMID- 26861000 TI - Non-Vitamin K Oral Anticoagulant Drugs for Stroke Prevention in Patients with Atrial Fibrillation and Chronic Kidney Disease. AB - Atrial fibrillation (AF) and chronic kidney disease (CKD) are disorders with increasing prevalence. The presence of CKD increases the risk of incident AF and vice versa, and the presence of AF may accelerate CKD progression. Nearly a third of patients with established CKD also have AF, whilst half of AF patients may have some degree of renal dysfunction. Both AF and CKD are associated with increased cardiovascular morbidity and mortality, including significantly increased risk of stroke or systemic embolism. Oral anticoagulant therapy (OAC), either with vitamin K antagonists or with non-vitamin K oral anticoagulants (NOACs) is essential to optimise prevention of stroke and systemic embolism in AF patients with one or more stroke risk factors, and NOACs are more convenient and generally safer than vitamin K antagonists mostly due to consistently reduced risk of intracranial bleeding. The use of OAC must be balanced against the risk of OAC-related bleeding, which depends on the presence of bleeding risk factors. Renal failure is a well-established bleeding risk factor and renal function should be routinely assessed in all patients presenting with AF. Since the risk of bleeding increases in parallel with CKD severity, the clinical decision to use OAC in AF patients with severe CKD may be challenging. In this review article we summarize the OAC agents currently used in clinical practice and discuss the role of NOACs for stroke prevention in patients with AF and CKD. PMID- 26861001 TI - Prevention of Renal Complications Induced by Non- Steroidal Anti-Inflammatory Drugs. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for the treatment of pain, inflamation and fever. They are usually well tolerated in healthy persons, but in patients with risk factors (advanced age, renal impairment, heart failure, liver disease, concurrent medications with antihypertensive drugs), NSAIDs can induce serious renal adverse effects. They include sodium and water retention with edema, worsening of heart failure, hypertension, hyponatremia, hyperkalemia, acute kidney injury, chronic kidney disease, renal papillary necrosis and acute interstitial nephritis. The majority of these adverse effects are due to the inhibition of prostaglandins synthesis and they are dose and duration-dependent. Acute forms of kidney injuries are transient and often reversible upon drug withdrawal. Chronic use of NSAIDs in some patients may result in chronic kidney disease. It is recommended that patients at risk should have preventative strategies in place, including the use of the "lowest effective dose" of NSAID for the "shortest possible time" and monitoring renal function, fluid retention and electrolyte abnormalities. Patients who are taking antihypertensive medications should be monitored for high blood pressure and the doses of antihypertensive medications should be adjusted if needed. In general, the combination of NSAIDs and angiotensin inhibitors should be avoided. Some other preventive measures are dietary salt restriction, use of topical NSAIDs/non-pharmacological therapies and use of calcium channel blockers for treating hypertension. PMID- 26861002 TI - Recent Developments of C-Aryl Glucoside SGLT2 Inhibitors. AB - Sodium-glucose cotransporter 2 (SGLT2) is almost exclusively expressed in the proximal renal tubules. It is responsible for about 90% of the glucose reabsorption from tubular fluid. Selective inhibition of SGLT2 is expected to favor in the normalization of plasma glucose levels in T2DM patients through the prevention of renal glucose reabsorption and the promotion of glucose excretion from urine. Selective SGLT2 inhibitors have the merits to minimize the gastrointestinal side effects associated with SGLT1 inhibition, and selective SGLT2 inhibition may have a low risk of hypoglycemia. Since the C-aryl glucosides are metabolically more stable than the O-glucosides, numerous efforts have been made in the development of potent and selective C-aryl glucoside SGLT2 inhibitors, and a number of them are now used as anti-diabetes drugs in clinic or at various stages of clinical developments. Based on their structural features, in this review, these SGLT2 inhibitors are classified as three types: the phenyl/arylmethylphenyl C-glucosides, with an emphasis on the modifications on the proximal and/or the distal phenyl ring, and the spacer; the heteroarylmethylphenyl Cglucosides, with a replacement of the distal phenyl ring by a heterocycle like pyridazine, pyrimidine, thiophene and benzothiophene, thiazole, 1,3,4-thiadiazole, and triazolopyridinone; and the glucose-modified Caryl glucosides, including the glucose C-1 derived O-spiroketals, C-4 gem difluoro analogues, C-5 and C-6 modified derivatives, dioxa-bicyclo[3.2.1]octane bridged ketals, the thioglucosides, and carbasugars. The structure-activity relationships (SARs) of each type along with their inhibitory potency against human SGLT2 and selectivity over human SGLT1 are discussed. PMID- 26861004 TI - An Overview of Non-Neural Sources of Calcitonin Gene-Related Peptide. AB - Calcitonin gene-related peptide (CGRP) is extensively distributed throughout the central and peripheral nervous systems and has been shown to be a 37 amino acid multifunctional neuropeptide involved in a wide range of physiological and pathological processes. Recently, there is increasing evidence suggesting that CGRP also exists in non-nerve cells, such as epithelial cells, endothelial cells, endothelial progenitor cells (EPCs), T lymphocytes, B lymphocytes, peripheral blood mononuclear cells (PBMCs), and adipocytes. The existence of CGRP in non neural tissue is of great importance to the regulation of multiple physiological and pathological processes via different pathways, especially through an autocrine/paracrine mode. This review integrates evidence from recent developments and aims to provide novel insights into non-neural sources of CGRP and its effects on physiological and pathological processes. PMID- 26861005 TI - Fight Against H1N1 Influenza A Virus: Recent Insights Towards the Development of Druggable Compounds. AB - In this review we discuss drug design strategies directed to the development of potential anti-influenza A(H1N1) inhibitors of M2 ion channel, neuraminidase (NA), hemagglutinin (HA) and RNA-dependent RNA-polymerase complex (RdRp) major targets, following temporal chronology of their findings. Besides searching for new chemotypes, eventually active against new targets of influenza A (H1N1), the design of optimized analogues of proven drugs is largely pursued, taking into account the emerging insight into the mechanisms of resistance to existing antivirals. Computational studies are also summarized, in order to highlight the structural requirements for further chemical optimizations. PMID- 26861003 TI - Recent Advances in Drug Design and Drug Discovery for Androgen- Dependent Diseases. AB - This article summarizes the importance of different targets such as 5alpha reductase, 17beta-HSD, CYP17A, androgen receptor and protein kinase A for the treatment of prostate cancer and benign prostatic hyperplasia. It is a well known fact that dihydrotestosterone (DHT) is associated with the development of androgen-dependent afflictions. At the present time, several research groups are attempting to develop new steroidal and non-steroidal molecules with the purpose of inhibiting the synthesis and biological response of DHT. This review also discusses the most recent studies reported in the literature that describe the therapeutic potential of novel compounds, as well as the new drugs, principally inhibitors of 5alpha-reductase. PMID- 26861006 TI - A Qualitative Analysis of Post-operative Nutritional Barriers and Useful Dietary Services Reported by Bariatric Surgical Patients. AB - BACKGROUND: Outcomes studies show many bariatric patients fail to lose optimal weight or regain significant weight post-surgery. One reason for weight regain may be difficulty adhering to the postoperative diet. METHODS: Cross-sectional survey methodology collected text data on perceived postoperative nutritional barriers and helpful dietary services reported by bariatric patients. Participants were solicited from an online obesity support website, and 440 responses related to perceived barriers and 330 responses regarding postoperative services were examined using inductive content analysis. RESULTS: Barriers were categorized as being Internal, External, and None. Internal barriers were classified as Psychological, Physiological, and Psychophysiological, with Psychophysiological being the most commonly reported (85.9 %). Helpful services reported included categories of None, Provided, and On their Own. Sixty-two percent of participants reported receiving at least one Provided service that was helpful, including knowledge and support from professionals like registered dietitian nutritionists (RDNs). However, 22 % of participants reported seeking out at least one service On their Own such as through the Internet, and 27 % of participants reported not receiving or not using any helpful services. CONCLUSIONS: The physiological nature of post-surgical changes and the mental stamina required of positive eating habits contribute to postoperative adherence difficulties. Many patients likely exhibit poor habits pre-surgery, and without added help to change these behaviors may regain weight. Participants in this study indicated that convenient access to an RDN was helpful. Bariatric facilities should include staff well-trained in the specific nutritional barriers patients face and provide availability of staff beyond the initial postoperative phase. PMID- 26861007 TI - Intraabdominal Pressure and Postoperative Discomfort in Laparoscopic Roux-en-Y Gastric Bypass (RYGB) Surgery: a Randomized Study. AB - BACKGROUND: High intraabdominal pressure (IAP) during laparoscopic surgery has been associated with postoperative discomfort. Effects on nausea and access have not been subjected to randomized studies. In cholecystectomy, lower IAP may cause less pain, but nausea and surgical access in RYGB surgery have not been investigated. We studied the influence of two IAP levels on surgical access, operation time, postoperative pain, and nausea. METHODS: Fifty consecutive female gastric bypass patients were randomized to intraabdominal pressure of 12 (IAP12) or 18 (IAP18) mm Hg. Surgeons and personnel were blinded to randomization; study groups were well matched for age and BMI. Operative time was noted in minutes. Visual analogue scales were used for assessing access and for patients assessing pain (abdomen-shoulder) and nausea (supine-standing) at six time points during the first 16 postoperative hours. Rescue medication was recorded. RESULTS: In 3/25 patients in the IAP12 group, the code was broken due to access problems vs. 0/25 in the IAP18 group (p = 0.1398). Operative time did not differ. Access was significantly better for IAP18 (92.2 +/- 2.3 vs. 69.3 +/- 4.2; p = 0.0001). Postoperative shoulder pain was maximal after 6 h but throughout less than in the abdomen (p < 0.0001); there were no differences in pain between IAP18 and IAP12 (p = 0.7408). Postoperative nausea was significantly greater standing than supine but without differences between groups. CONCLUSION: Higher IAP gives better surgical access in laparoscopic Roux-en-Y gastric bypass with no negative effect on pain or nausea. PMID- 26861008 TI - Cardiovascular Risk Factors in Gastric Cancer Patients Decrease 1 Year After Gastrectomy. AB - BACKGROUND: Due to the high 5-year overall survival rate (>95 %) for early gastric cancer (EGC), patients now face risks of developing comorbidities. Cardiovascular disease (CVD) is one of the most common causes of death not only in the general population and but also in cancer patients. Thus, we determined the effect of gastrectomy on cardiovascular risk factors by analyzing changes in lipid profiles of patients who underwent curative gastrectomy for EGC. METHODS: Seventy-three patients who received curative gastrectomy for EGC were included and divided into gastroduodenostomy (GD) and duodenal bypass (DB) groups according to the anastomosis. Changes in visceral fat area (VFA), subcutaneous fat area (SFA), and lipid profiles [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] were evaluated in both groups 1 year after gastrectomy. RESULTS: Body weight, VFA, SFA, TG, LDL-C, and TC decreased significantly while HDL-C increased (p < 0.001) after the surgery. We observed a weak negative correlation between percent change of VFA and HDL-C (r = -0.245, p = 0.036). When compared with the GD group, the DB group lost more SFA (p < 0.001), body weight (p = 0.008), and TC (p = 0.031). We also found that the degree of BMI change (?BMI) was greater in the obese patients than in the non-obese patients (p < 0.001). CONCLUSIONS: Curative gastrectomy reduces VFA, SFA, and body weight and improves lipid profiles in patients with EGC, all of which indicates reduced cardiovascular risk. Therefore, prospective studies are required to verify whether gastrectomy in EGC patients has favorable effects on future CVD mortality. PMID- 26861009 TI - Ventricular volume and neurocognitive outcome after endoscopic third ventriculostomy: is shunting a better option? A review. AB - BACKGROUND: Shunts are generally associated with a smaller post-treatment ventricular size in comparison to endoscopic third ventriculostomy (ETV). METHODS: To determine whether such a difference in ventricular size has neurocognitive implications, we reviewed the current literature pertaining to the (1) neurocognitive sequelae of hydrocephalus, (2) neurocognitive outcome after ETV, (3) extent of reversal of neurocognitive changes associated with hydrocephalus after shunting, and (4) data on correlation between post-treatment ventricular volume and neurocognitive outcome after ETV. RESULTS: Collectively, the results of the available studies should call into question the correlation between the residual postoperative ventricular volume and neurocognitive outcome. CONCLUSION: The available literature is so far in support of ETV as a valid and effective treatment modality in hydrocephalic patients. No sufficient evidence is available to justify resorting to shunting on the premise that it is associated with a better neurocognitive outcome. PMID- 26861010 TI - Precision diagnosis and antidiastole on supernumerary cusp of tooth by CBCT. AB - PURPOSE: Based on a case of supernumerary cusp on the bucca of left maxillary second molar diagnosed by cone beam computed tomography (CBCT), its genesis, diagnosis and antidiastole are to be analysed. The clinic implication of CBCT is correspondingly discussed. METHODS: The supernumerary cusp was diagnosed by oral general examination, intra-oral radiograph and CBCT. The features of supernumerary cusp, fused tooth, geminated tooth and concrescence tooth, especially differentiate points among them were discussed. RESULTS: The case of supernumerary cusp on the bucca of left maxillary second molar was diagnosed definitely by the combined application of oral general examination, periapical radiograph and CBCT. CONCLUSION: Supernumerary cusp on the bucca of left maxillary second molar is a rare phenomenon, which is difficult to be differentiated from other tooth deformities. CBCT can improve accuracy of diagnosis. PMID- 26861011 TI - Cadaveric study of anterior and posterior elbow endoscopy portals for endoscopic distal biceps repair: comparative anatomy-at-risk. AB - PURPOSE: The purpose of this study was to describe neurovascular structures-at risk during establishment of five portals for access to distal biceps tendon (DBT) in cubital fossa, and to establish relative safety of these portal sites for such access. We hypothesized that all five portals are safe for endoscopic DBT exploration. METHODS: Ten fresh frozen cadaveric elbows were dissected after placement of portals at five potential sites (four anterior, one posterior). Nine neurovascular structures (CV, cephalic vein; LCN, lateral cutaneous nerve; LV, leash of vessels; RN, radial nerve; SRN, superficial radial nerve; PIN, posterior interosseous nerve; RA, radial artery; BA, brachial artery; MN, median nerve) were dissected, and their distances from portal sites were measured. Statistical analysis was performed to determine relative portal safety, and risk of injury to neurovascular structures in relation to each portal was analyzed. RESULTS: Structures that were significantly "at risk" were RA (p = 0.006), SRN (p = 0.002), and PIN (p = 0.004). RA was significantly "at risk" of injury from portal 4 (p = 0.009). Similarly, SRN was "at risk" from portal 3 (p = 0.036), and the PIN was "at risk" from portal 2 (p = 0.003). CONCLUSIONS: Portal 1 (parabiceps portal) was safe for all neurovascular structures, however, portals 2-4 were significantly closer to neurovascular structures. RA, SRN, and PIN were significantly "at risk" as compared to other structures amongst the portals studied. Portal 5 was relatively safe for SRN and PIN. CLINICAL RELEVANCE: Portals 1 (parabiceps portal) and 5 (distal posterior) can be safely placed for endoscopic access to the DBT. Portal 4 (open distal anterior) may be used after careful open dissection and under direct vision. Portals 2 and 3 are not recommended for elbow endoscopy. PMID- 26861012 TI - An undetected common renal arterial trunk: surgical consequences and morbidity analysis. AB - We present a patient with a recurrent precaval left renal artery, stemming from a right-sided common trunk renal artery. The patient was a 44-year male who presented with a post-traumatic grade IV renal injury. After 3 months without renal function improvement and repeated urinary tract infection, a laparoscopic nephrectomy of the affected right kidney was performed, without upfront identification of the vascular variation, resulting in ischemia of the remaining left kidney. An anastomosis of the common renal trunk and the distal left renal artery was created in between the abdominal aorta and the inferior vena cava. This case describes the importance of upfront detection of renal vascular variations using the appropriate imaging techniques. PMID- 26861013 TI - Morphometric study of the two fused primary ossification centers of the clavicle in the human fetus. AB - PURPOSES: A satisfactory understanding of the clavicle development may be contributing to both the diagnosis of its congenital defects and prevention of perinatal damage to the shoulder girdle. This study was carried out to examine the transverse and sagittal diameters, cross-sectional area and volume of the two fused primary ossification centers of the clavicle. METHODS: Using the methods of CT, digital-image analysis and statistics, the size for two fused primary ossification centers of the clavicle in 42 spontaneously aborted human fetuses at ages of 18-30 weeks was studied. RESULTS: Without any male-female and right-left significant differences, the best fit growth models for two fused primary ossification centers of the clavicle were as follows: y = -31.373 + 15.243 * ln(age) +/- 1.424 (R (2) = 0.74) for transverse diameter, y = -7.945 + 3.225 * ln(age) +/- 0.262 (R (2) = 0.78), y = -4.503 + 2.007 * ln(age) +/- 0.218 (R (2) = 0.68), and y = -4.860 + 2.117 * ln(age) +/- 0.200 (R (2) = 0.73) for sagittal diameters of the lateral, middle and medial ends respectively, y = -31.390 + 2.432 * age +/- 4.599 (R (2) = 0.78) for cross-sectional area, and y = 28.161 + 0.00017 * (age)(4) +/- 15.357 (R (2) = 0.83) for volume. CONCLUSIONS: With no sex and laterality differences, the fused primary ossification centers of the clavicle grow logarithmically in both transverse and sagittal diameters, linearly in cross-sectional area, and fourth-degree polynomially in volume. Our normative quantitative findings may be conducive in monitoring normal fetal growth and screening for inherited faults and anomalies of the clavicle in European human fetuses. PMID- 26861014 TI - Unveiling Protein Kinase A Targets in Cryptococcus neoformans Capsule Formation. AB - The protein kinase A (PKA) signal transduction pathway has been associated with pathogenesis in many fungal species. Geddes and colleagues [mBio 7(1):e01862-15, 2016, doi:10.1128/mBio.01862-15] used quantitative proteomics approaches to define proteins with altered abundance during protein kinase A (PKA) activation and repression in the opportunistic human fungal pathogen Cryptococcus neoformans. They observed an association between microbial PKA signaling and ubiquitin-proteasome regulation of protein homeostasis. Additionally, they correlated these processes with expression of polysaccharide capsule on the fungal cell surface, the main virulence-associated phenotype in this organism. Not only are their findings important for microbial pathogenesis, but they also support similar associations between human PKA signaling and ubiquitinated protein accumulation in neurodegenerative diseases. PMID- 26861015 TI - Direct Visualization of Ebola Virus Fusion Triggering in the Endocytic Pathway. AB - Ebola virus (EBOV) makes extensive and intricate use of host factors in the cellular endosomal/lysosomal pathway to release its genome into the cytoplasm and initiate infection. Following viral internalization into endosomes, host cysteine proteases cleave the EBOV fusion glycoprotein (GP) to unmask the binding site for its intracellular receptor, the cholesterol transporter Niemann-Pick C1 (NPC1). GP-NPC1 interaction is required for viral entry. Despite these and other recent discoveries, late events in EBOV entry following GP-NPC1 binding and culminating in GP-catalyzed fusion between viral and cellular lipid bilayers remain enigmatic. A mechanistic understanding of EBOV membrane fusion has been hampered by the failure of previous efforts to reconstitute fusion in vitro or at the cell surface. This report describes an assay to monitor initial steps directly in EBOV membrane fusion-triggering of GP and virus-cell lipid mixing-by single virions in live cells. Fusogenic triggering of GP occurs predominantly in Rab7-positive (Rab7(+)) endosomes, absolutely requires interaction between proteolytically primed GP and NPC1, and is blocked by key GP-specific neutralizing antibodies with therapeutic potential. Unexpectedly, cysteine protease inhibitors do not inhibit lipid mixing by virions bearing precleaved GP, even though they completely block cytoplasmic entry by these viruses, as shown previously. These results point to distinct cellular requirements for different steps in EBOV membrane fusion and suggest a model in which host cysteine proteases are dispensable for GP fusion triggering after NPC1 binding but are required for the formation of fusion pores that permit genome delivery. IMPORTANCE: Ebola virus (EBOV) causes outbreaks of highly lethal disease for which no approved vaccines or treatments exist. Recent work has elucidated key molecular features of the complex EBOV entry process, including stepwise interactions with multiple host factors. However, there is a critical gap in our understanding of events that surround the final membrane fusion step which persists due to the paucity of direct and extensive investigation of EBOV fusion. Here, we report a real-time assay for EBOV glycoprotein fusion triggering and use it to define its cellular location and requirements. We also uncover an unexpected requirement for host proteases at a step after fusion triggering that may reflect their role in formation of fusion pores for genome delivery. PMID- 26861017 TI - Lambda Interferon Restructures the Nasal Microbiome and Increases Susceptibility to Staphylococcus aureus Superinfection. AB - Much of the morbidity and mortality associated with influenza virus respiratory infection is due to bacterial coinfection with pathogens that colonize the upper respiratory tract such as methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae. A major component of the immune response to influenza virus is the production of type I and III interferons. Here we show that the immune response to infection with influenza virus causes an increase and restructuring of the upper respiratory microbiota in wild-type (WT) mice but not in Il28r(-/-) mutant mice lacking the receptor for type III interferon. Mice lacking the IL-28 receptor fail to induce STAT1 phosphorylation and expression of its regulator, SOCS1. Il28r(-/-) mutant mice have increased expression of interleukin-22 (IL-22), as well as Ngal and RegIIIgamma, in the nasal cavity, the source of organisms that would be aspirated to cause pneumonia. Proteomic analysis reveals changes in several cytoskeletal proteins that contribute to barrier function in the nasal epithelium that may contribute to the effects of IL 28 signaling on the microbiota. The importance of the effects of IL-28 signaling in the pathogenesis of MRSA pneumonia after influenza virus infection was confirmed by showing that WT mice nasally colonized before or after influenza virus infection had significantly higher levels of infection in the upper airways, as well as significantly greater susceptibility to MRSA pneumonia than Il28r(-/-) mutant mice did. Our results suggest that activation of the type III interferon in response to influenza virus infection has a major effect in expanding the upper airway microbiome and increasing susceptibility to lower respiratory tract infection. IMPORTANCE: S. aureus and influenza virus are important respiratory pathogens, and coinfection with these organisms is associated with significant morbidity and mortality. The ability of influenza virus to increase susceptibility to S. aureus infection is less well understood. We show here that influenza virus leads to a change in the upper airway microbiome in a type III interferon-dependent manner. Mice lacking the type III interferon receptor have altered STAT1 and IL-22 signaling. In coinfection studies, mice without the type III interferon receptor had significantly less nasal S. aureus colonization and subsequent pneumonia than infected WT mice did. This work demonstrates that type III interferons induced by influenza virus contribute to nasal colonization and pneumonia due to S. aureus superinfection. PMID- 26861016 TI - The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Functions as a Novel Cytosolic Pathogen-Associated Molecular Pattern To Promote Beta Interferon Induction via a Toll-Like-Receptor-Related TRAF3-Independent Mechanism. AB - Most of the intracellular pattern recognition receptors (PRRs) reside in either the endolysosome or the cytoplasm to sense pathogen-derived RNAs, DNAs, or synthetic analogs of double-stranded RNA (dsRNA), such as poly(I:C). However, it remains elusive whether or not a pathogen-derived protein can function as a cytosolic pathogen-associated molecular pattern (PAMP). In this study, we demonstrate that delivering the membrane gene of severe acute respiratory syndrome coronavirus (SARS-CoV) into HEK293T, HEK293ET, and immobilized murine bone marrow-derived macrophage (J2-Mphi) cells significantly upregulates beta interferon (IFN-beta) production. Both NF-kappaB and TBK1-IRF3 signaling cascades are activated by M gene products. M protein rather than M mRNA is responsible for M-mediated IFN-beta induction that is preferentially associated with the activation of the Toll-like receptor (TLR) adaptor proteins MyD88, TIRAP, and TICAM2 but not the RIG-I signaling cascade. Blocking the secretion of M protein by brefeldin A (BFA) failed to reverse the M-mediated IFN-beta induction. The antagonist of both TLR2 and TLR4 did not impede M-mediated IFN-beta induction, indicating that the driving force for the activation of IFN-beta production was generated from inside the cells. Inhibition of TRAF3 expression by specific small interfering RNA (siRNA) did not prevent M-mediated IFN-beta induction. SARS-CoV pseudovirus could induce IFN-beta production in an M rather than M(V68A) dependent manner, since the valine-to-alanine alteration at residue 68 in M protein markedly inhibited IFN-beta production. Overall, our study indicates for the first time that a pathogen-derived protein is able to function as a cytosolic PAMP to stimulate type I interferon production by activating a noncanonical TLR signaling cascade in a TRAF3-independent manner. IMPORTANCE: Viral protein can serve as a pathogen-associated molecular pattern (PAMP) that is usually recognized by certain pathogen recognition receptors (PRRs) on the cell surface, such as Toll-like receptor 2 (TLR2) and TLR4. In this study, we demonstrate that the membrane (M) protein of SARS-CoV can directly promote the activation of both beta interferon (IFN-beta) and NF-kappaB through a TLR-related signaling pathway independent of TRAF3. The driving force for M-mediated IFN-beta production is most likely generated from inside the cells. M-mediated IFN-beta induction was confirmed at the viral infection level since a point mutation at the V68 residue of M markedly inhibited SARS-CoV pseudovirally induced IFN-beta production. Thus, the results indicate for the first time that SARS-CoV M protein may function as a cytosolic PAMP to stimulate IFN-beta production by activating a TLR-related TRAF3 independent signaling cascade. PMID- 26861018 TI - Resolving the Complexity of Human Skin Metagenomes Using Single-Molecule Sequencing. AB - Deep metagenomic shotgun sequencing has emerged as a powerful tool to interrogate composition and function of complex microbial communities. Computational approaches to assemble genome fragments have been demonstrated to be an effective tool for de novo reconstruction of genomes from these communities. However, the resultant "genomes" are typically fragmented and incomplete due to the limited ability of short-read sequence data to assemble complex or low-coverage regions. Here, we use single-molecule, real-time (SMRT) sequencing to reconstruct a high quality, closed genome of a previously uncharacterized Corynebacterium simulans and its companion bacteriophage from a skin metagenomic sample. Considerable improvement in assembly quality occurs in hybrid approaches incorporating short read data, with even relatively small amounts of long-read data being sufficient to improve metagenome reconstruction. Using short-read data to evaluate strain variation of this C. simulans in its skin community at single-nucleotide resolution, we observed a dominant C. simulans strain with moderate allelic heterozygosity throughout the population. We demonstrate the utility of SMRT sequencing and hybrid approaches in metagenome quantitation, reconstruction, and annotation. IMPORTANCE: The species comprising a microbial community are often difficult to deconvolute due to technical limitations inherent to most short-read sequencing technologies. Here, we leverage new advances in sequencing technology, single-molecule sequencing, to significantly improve reconstruction of a complex human skin microbial community. With this long-read technology, we were able to reconstruct and annotate a closed, high-quality genome of a previously uncharacterized skin species. We demonstrate that hybrid approaches with short read technology are sufficiently powerful to reconstruct even single-nucleotide polymorphism level variation of species in this a community. PMID- 26861019 TI - Vaccine and Wild-Type Strains of Yellow Fever Virus Engage Distinct Entry Mechanisms and Differentially Stimulate Antiviral Immune Responses. AB - The live attenuated yellow fever virus (YFV) vaccine 17D stands as a "gold standard" for a successful vaccine. 17D was developed empirically by passaging the wild-type Asibi strain in mouse and chicken embryo tissues. Despite its immense success, the molecular determinants for virulence attenuation and immunogenicity of the 17D vaccine are poorly understood. 17D evolved several mutations in its genome, most of which lie within the envelope (E) protein. Given the major role played by the YFV E protein during virus entry, it has been hypothesized that the residues that diverge between the Asibi and 17D E proteins may be key determinants of attenuation. In this study, we define the process of YFV entry into target cells and investigate its implication in the activation of the antiviral cytokine response. We found that Asibi infects host cells exclusively via the classical clathrin-mediated endocytosis, while 17D exploits a clathrin-independent pathway for infectious entry. We demonstrate that the mutations in the 17D E protein acquired during the attenuation process are sufficient to explain the differential entry of Asibi versus 17D. Interestingly, we show that 17D binds to and infects host cells more efficiently than Asibi, which culminates in increased delivery of viral RNA into the cytosol and robust activation of the cytokine-mediated antiviral response. Overall, our study reveals that 17D vaccine and Asibi enter target cells through distinct mechanisms and highlights a link between 17D attenuation, virus entry, and immune activation. IMPORTANCE: The yellow fever virus (YFV) vaccine 17D is one of the safest and most effective live virus vaccines ever developed. The molecular determinants for virulence attenuation and immunogenicity of 17D are poorly understood. 17D was generated by serially passaging the virulent Asibi strain in vertebrate tissues. Here we examined the entry mechanisms engaged by YFV Asibi and the 17D vaccine. We found the two viruses use different entry pathways. We show that the mutations differentiating the Asibi envelope (E) protein from the 17D E protein, which arose during attenuation, are key determinants for the use of these distinct entry routes. Finally, we demonstrate that 17D binds and enters host cells more efficiently than Asibi. This results in a higher uptake of viral RNA into the cytoplasm and consequently a greater cytokine-mediated antiviral response. Overall, our data provide new insights into the biology of YFV infection and the mechanisms of viral attenuation. PMID- 26861020 TI - Genome-wide Annotation, Identification, and Global Transcriptomic Analysis of Regulatory or Small RNA Gene Expression in Staphylococcus aureus. AB - In Staphylococcus aureus, hundreds of small regulatory or small RNAs (sRNAs) have been identified, yet this class of molecule remains poorly understood and severely understudied. sRNA genes are typically absent from genome annotation files, and as a consequence, their existence is often overlooked, particularly in global transcriptomic studies. To facilitate improved detection and analysis of sRNAs in S. aureus, we generated updated GenBank files for three commonly used S. aureus strains (MRSA252, NCTC 8325, and USA300), in which we added annotations for >260 previously identified sRNAs. These files, the first to include genome wide annotation of sRNAs in S. aureus, were then used as a foundation to identify novel sRNAs in the community-associated methicillin-resistant strain USA300. This analysis led to the discovery of 39 previously unidentified sRNAs. Investigating the genomic loci of the newly identified sRNAs revealed a surprising degree of inconsistency in genome annotation in S. aureus, which may be hindering the analysis and functional exploration of these elements. Finally, using our newly created annotation files as a reference, we perform a global analysis of sRNA gene expression in S. aureus and demonstrate that the newly identified tsr25 is the most highly upregulated sRNA in human serum. This study provides an invaluable resource to the S. aureus research community in the form of our newly generated annotation files, while at the same time presenting the first examination of differential sRNA expression in pathophysiologically relevant conditions. IMPORTANCE: Despite a large number of studies identifying regulatory or small RNA (sRNA) genes in Staphylococcus aureus, their annotation is notably lacking in available genome files. In addition to this, there has been a considerable lack of cross-referencing in the wealth of studies identifying these elements, often leading to the same sRNA being identified multiple times and bearing multiple names. In this work, we have consolidated and curated known sRNA genes from the literature and mapped them to their position on the S. aureus genome, creating new genome annotation files. These files can now be used by the scientific community at large in experiments to search for previously undiscovered sRNA genes and to monitor sRNA gene expression by transcriptome sequencing (RNA-seq). We demonstrate this application, identifying 39 new sRNAs and studying their expression during S. aureus growth in human serum. PMID- 26861021 TI - Host RNA Packaging by Retroviruses: A Newly Synthesized Story. AB - A fascinating aspect of retroviruses is their tendency to nonrandomly incorporate host cell RNAs into virions. In addition to the specific tRNAs that prime reverse transcription, all examined retroviruses selectively package multiple host cell noncoding RNAs (ncRNAs). Many of these ncRNAs appear to be encapsidated shortly after synthesis, before assembling with their normal protein partners. Remarkably, although some packaged ncRNAs, such as pre-tRNAs and the spliceosomal U6 small nuclear RNA (snRNA), were believed to reside exclusively within mammalian nuclei, it was demonstrated recently that the model retrovirus murine leukemia virus (MLV) packages these ncRNAs from a novel pathway in which unneeded nascent ncRNAs are exported to the cytoplasm for degradation. The finding that retroviruses package forms of ncRNAs that are rare in cells suggests several hypotheses for how these RNAs could assist retrovirus assembly and infectivity. Moreover, recent experiments in several laboratories have identified additional ways in which cellular ncRNAs may contribute to the retrovirus life cycle. This review focuses on the ncRNAs that are packaged by retroviruses and the ways in which both encapsidated ncRNAs and other cellular ncRNAs may contribute to retrovirus replication. PMID- 26861023 TI - Two Cyanobacterial Photoreceptors Regulate Photosynthetic Light Harvesting by Sensing Teal, Green, Yellow, and Red Light. AB - The genomes of many photosynthetic and nonphotosynthetic bacteria encode numerous phytochrome superfamily photoreceptors whose functions and interactions are largely unknown. Cyanobacterial genomes encode particularly large numbers of phytochrome superfamily members called cyanobacteriochromes. These have diverse light color-sensing abilities, and their functions and interactions are just beginning to be understood. One of the best characterized of these functions is the regulation of photosynthetic light-harvesting antenna composition in the cyanobacterium Fremyella diplosiphon by the cyanobacteriochrome RcaE in response to red and green light, a process known as chromatic acclimation. We have identified a new cyanobacteriochrome named DpxA that maximally senses teal (absorption maximum, 494 nm) and yellow (absorption maximum, 568 nm) light and represses the accumulation of a key light-harvesting protein called phycoerythrin, which is also regulated by RcaE during chromatic acclimation. Like RcaE, DpxA is a two-component system kinase, although these two photoreceptors can influence phycoerythrin expression through different signaling pathways. The peak responsiveness of DpxA to teal and yellow light provides highly refined color discrimination in the green spectral region, which provides important wavelengths for photosynthetic light harvesting in cyanobacteria. These results redefine chromatic acclimation in cyanobacteria and demonstrate that cyanobacteriochromes can coordinately impart sophisticated light color sensing across the visible spectrum to regulate important photosynthetic acclimation processes. IMPORTANCE: The large number of cyanobacteriochrome photoreceptors encoded by cyanobacterial genomes suggests that these organisms are capable of extremely complex light color sensing and responsiveness, yet little is known about their functions and interactions. Our work uncovers previously undescribed cooperation between two photoreceptors with very different light color-sensing capabilities that coregulate an important photosynthetic light-harvesting protein in response to teal, green, yellow, and red light. Other cyanobacteriochromes that have been shown to interact functionally sense wavelengths of light that are close to each other, which makes it difficult to clearly identify their physiological roles in the cell. Our finding of two photoreceptors with broad light color-sensing capabilities and clearly defined physiological roles provides new insights into complex light color sensing and its regulation. PMID- 26861024 TI - Subclavian steal: Endovascular treatment of total occlusions of the subclavian artery using a retrograde transradial subintimal approach. AB - INTRODUCTION: In symptomatic subclavian steal syndrome, endovascular treatment is the first line of therapy prior to extra-anatomic surgical bypass procedures. Subintimal recanalization has been well described in the literature for the coronary arteries, and more recently, in the lower extremities. By modifying this approach, we present a unique retrograde technique using a heavy tip microwire to perform controlled subintimal dissection. METHODS: We present two cases of symptomatic subclavian steal related to chronic total occlusion of the left subclavian artery and right innominate artery, respectively. Standard crossing techniques were unsuccessful. Commonly at this point, the procedures would be aborted and open surgical intervention would have to be pursued. In our cases, retrograde access was easily achieved via an ipsilateral retrograde radial artery, using controlled subintimal dissection and a heavy-tipped wire. RESULTS: We were able to easily achieve recanalization in both attempted cases of chronic total occlusion of the subclavian and innominate artery, using a retrograde radial subintimal approach. Subsequent stent-supported angioplasty resulted in complete revascularization. No major complications were encountered during the procedures; however, one patient did develop thromboembolic stroke secondary to platelet aggregation to the stent graft, 9 days post-procedure. CONCLUSIONS: Endovascular treatment is considered the first-line intervention in medically refractory patients with symptomatic subclavian steal syndrome. In the setting of chronic total occlusions, a retrograde radial subintimal approach using a heavy tip wire for controlled subintimal dissection is a novel technique that may be considered when standard approaches and wires have failed. PMID- 26861025 TI - Therapeutic internal carotid or vertebral artery occlusion using the WEB device. AB - The WEB device was used to occlude the internal carotid artery or vertebral artery as treatment for large aneurysms. The WEB could be placed accurately at the desired position inside the vessel. Two WEBs were sufficient to occlude the parent artery. PMID- 26861022 TI - The Staphylococcus aureus Methicillin Resistance Factor FmtA Is a d-Amino Esterase That Acts on Teichoic Acids. AB - The methicillin resistance factor encoded by fmtA is a core member of the Staphylococcus aureus cell wall stimulon, but its function has remained elusive for the past two decades. First identified as a factor that affects methicillin resistance in S. aureus strains, FmtA was later shown to interact with teichoic acids and to localize to the cell division septum. We have made a breakthrough in understanding FmtA function. We show that FmtA hydrolyzes the ester bond between d-Ala and the backbone of teichoic acids, which are polyglycerol-phosphate or polyribitol-phosphate polymers found in the S. aureus cell envelope. FmtA contains two conserved motifs found in serine active-site penicillin-binding proteins (PBPs) and beta-lactamases. The conserved SXXK motif was found to be important for the d-amino esterase activity of FmtA. Moreover, we show that deletion of fmtA (DeltafmtA) led to higher levels of d-Ala in teichoic acids, and this effect was reversed by complementation of DeltafmtA with fmtA. The positive charge on d-Ala partially masks the negative charge of the polyol-phosphate backbone of teichoic acids; hence, a change in the d-Ala content will result in modulation of their charge. Cell division, biofilm formation, autolysis, and colonization are among the many processes in S. aureus affected by the d-Ala content and overall charge of the cell surface teichoic acids. The esterase activity of FmtA and the regulation of fmtA suggest that FmtA functions as a modulator of teichoic acid charge, thus FmtA may be involved in S. aureus cell division, biofilm formation, autolysis, and colonization. IMPORTANCE: Teichoic acids are involved in cell division, cell wall synthesis, biofilm formation, attachment of bacteria to artificial surfaces, and colonization. However, the function of teichoic acids is not fully understood. Modification by glycosylation and/or d-alanylation of the polyol-phosphate backbone of teichoic acids is important in the above cell processes. The intrinsic negative charge of teichoic acid backbone plays a role in the charge and/or pH of the bacterial surface, and d-alanylation represents a means through which bacteria modulate the charge or the pH of their surfaces. We discovered that FmtA removes d-Ala from teichoic acids. We propose FmtA may provide a temporal and spatial regulation of the bacterial cell surface charge in two ways, by removing the d-Ala from LTA to make it available to wall teichoic acid (WTA) in response to certain conditions and by removing it from WTA to allow the cell to reset its surface charge to a previous condition. PMID- 26861027 TI - Lesinurad: First Global Approval. AB - Lesinurad (ZURAMPIC((r))) is an oral urate-anion exchanger transporter 1 (URAT1) inhibitor developed by Ardea Biosciences (a subsidiary of AstraZeneca) for the treatment of hyperuricaemia associated with gout. It reduces serum uric acid (sUA) levels by inhibiting the function of the transporter proteins (URAT1 and organic anion transporter 4) involved in uric acid reabsorption in the kidney. In December 2015, lesinurad was approved in the USA as combination therapy with a xanthine oxidase inhibitor for the treatment of hyperuricaemia associated with gout in patients who have not achieved sUA target levels with a xanthine oxidase inhibitor alone. Lesinurad has also received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for this indication and is in phase III development as a combination therapy in several other countries. This article summarizes the milestones in the development of lesinurad leading to this first approval for hyperuricaemia associated with gout. PMID- 26861026 TI - Chronic non-cancer pain and the epidemic prescription of opioids in the Danish population: trends from 2000 to 2013. AB - BACKGROUND: Chronic pain has serious consequences for individuals and society. In addition, opioid prescription for chronic non-cancer pain (CNCP) has become more frequent. This study aims to examine the trends regarding the prevalence of CNCP, dispensed opioids, and concurrent use of benzodiazepine (BZD)/BZD-related drugs in the Danish population. METHODS: Data from the cross-sectional national representative Danish Health and Morbidity Surveys (2000, 2005, 2010, and 2013) were combined with The Danish National Prescription Registry at an individual level. The study populations varied between 5000 and 13,000 individuals >=16 years (response rates: 51-63%). Respondents completed a self-administered questionnaire, which included the analyzed items on identification of chronic pain (>=6 months). RESULTS: From 2000 to 2013, the prevalence of CNCP increased and subsequently the annual prevalence of opioid use from 4.1% to 5.7% among CNCP individuals. Higher CNCP prevalence was related to female gender, no cohabitation partner, short education, non-Western origin, and overweight/obesity. In addition, women with CNCP, especially >65 years, became more frequent users of opioids and used higher doses than men. Concurrent use of BZD/BZD-related drugs decreased (13%) from 2010 to 2013, still one-third of long-term opioid user were co-medicated with these drugs. CONCLUSIONS: The use of opioids has increased in Denmark, especially among elderly women. The concurrent use of BZD/BZD-related drugs has decreased from 2010 to 2013, but still one-third of long-term opioid users were co-medicated. PMID- 26861028 TI - Soy isoflavone exposure through all life stages accelerates 17beta-estradiol induced mammary tumor onset and growth, yet reduces tumor burden, in ACI rats. AB - There is an ongoing debate whether the intake of soy-derived isoflavones (sISO) mediates beneficial or adverse effects with regard to breast cancer risk. Therefore, we investigated whether nutritional exposure to a sISO-enriched diet from conception until adulthood impacts on 17beta-estradiol (E2)-induced carcinogenesis in the rat mammary gland (MG). August-Copenhagen-Irish (ACI) rats were exposed to dietary sISO from conception until postnatal day 285. Silastic tubes containing E2 were used to induce MG tumorigenesis. Body weight, food intake, and tumor growth were recorded weekly. At necropsy, the number, position, size, and weight of each tumor were determined. Plasma samples underwent sISO analysis, and the morphology of MG was analyzed. Tumor incidence and multiplicity were reduced by 20 and 56 %, respectively, in the sISO-exposed rats compared to the control rats. Time-to-tumor onset was shortened from 25 to 20 weeks, and larger tumors developed in the sISO-exposed rats. The histological phenotype of the MG tumors was independent of the sISO diet received, and it included both comedo and cribriform phenotypes. Morphological analyses of the whole-mounted MGs also showed no diet-dependent differences. Lifelong exposure to sISO reduced the overall incidence of MG carcinomas in ACI rats, although the time-to-tumor was significantly shortened. PMID- 26861029 TI - Partially supervised P300 speller adaptation for eventual stimulus timing optimization: target confidence is superior to error-related potential score as an uncertain label. AB - OBJECTIVE: Error-related potentials (ErrPs) have the potential to guide classifier adaptation in BCI spellers, for addressing non-stationary performance as well as for online optimization of system parameters, by providing imperfect or partial labels. However, the usefulness of ErrP-based labels for BCI adaptation has not been established in comparison to other partially supervised methods. Our objective is to make this comparison by retraining a two-step P300 speller on a subset of confident online trials using naive labels taken from speller output, where confidence is determined either by (i) ErrP scores, (ii) posterior target scores derived from the P300 potential, or (iii) a hybrid of these scores. We further wish to evaluate the ability of partially supervised adaptation and retraining methods to adjust to a new stimulus-onset asynchrony (SOA), a necessary step towards online SOA optimization. APPROACH: Eleven consenting able-bodied adults attended three online spelling sessions on separate days with feedback in which SOAs were set at 160 ms (sessions 1 and 2) and 80 ms (session 3). A post hoc offline analysis and a simulated online analysis were performed on sessions two and three to compare multiple adaptation methods. Area under the curve (AUC) and symbols spelled per minute (SPM) were the primary outcome measures. MAIN RESULTS: Retraining using supervised labels confirmed improvements of 0.9 percentage points (session 2, p < 0.01) and 1.9 percentage points (session 3, p < 0.05) in AUC using same-day training data over using data from a previous day, which supports classifier adaptation in general. SIGNIFICANCE: Using posterior target score alone as a confidence measure resulted in the highest SPM of the partially supervised methods, indicating that ErrPs are not necessary to boost the performance of partially supervised adaptive classification. Partial supervision significantly improved SPM at a novel SOA, showing promise for eventual online SOA optimization. PMID- 26861030 TI - Clinical characteristics of human brucellosis in patients with various monoarticular involvements. AB - The aim of the study was to determine the main demographic, epidemiological, clinical characteristics, and outcome in patients with various types of brucellar monoarticular involvement. Retrospectively, we analyzed medical histories of 331 patients with brucellar monoarticular involvement who were treated at the infectious diseases departments in Prilep, Shtip, and Veles, Republic of Macedonia, during the period 1990-2012. Their data were compared accordingly to the affected joint (sacroiliac, hip, knee, ankle, wrist, and shoulder).Patients with shoulder arthritis were significantly the oldest (mean +/- standard deviation [SD] 46.0 +/- 14.5 years) whereas sacroiliitis and hip arthritis were present predominantly in younger patients (mean +/- SD 28.7 +/- 14.1 and 28.3 +/- 18.3 years, respectively) (p = 0.014). Shoulder arthritis duration was significantly the longest (mean +/- SD 24.5 +/- 12.4 days), and wrist arthritis duration was significantly the shortest (mean +/- SD 4.1 +/- 2.5 days) (p < 0.001), before establishing the diagnosis of brucellosis. With appropriate treatment, the need for restitution of the joint impairment was significantly longer when sacroiliitis and hip arthritis were present (mean +/- SD 32.8 +/- 23.0 and 24.6 +/- 12.5 days, respectively) (p < 0.001). The relapses were noted in 14.5, 14, 16.5, 5.5, 6, and 5.5 % of the patients with sacroiliitis, hip-, shoulder-, knee-, ankle-. and wrist arthritis, respectively. In endemic areas, brucellosis should be included in the differential diagnostic consideration in patients with monoarticular involvement. Knee-, ankle-, and wrist arthritis seem to be more benign and with appropriate treatment result in short duration and satisfactory outcome. On the other hand, the involvement of sacroiliac, hip-, and shoulder joint deserves more serious approach due to longer arthritis duration and higher frequency of relapses. PMID- 26861031 TI - Can thyroid volume predict thyroid dysfunction in patients with systemic sclerosis? A prospective cross-sectional study from a tertiary care center in North West India. AB - Previous studies have documented an association between thyroid dysfunction, predominant hypothyroidism, and antibody positivity in patients with systemic sclerosis (SSc). There are no studies reporting the relationship between thyroid volume and thyroid functions in patients with SSc. This study was conducted to correlate thyroid dysfunction with thyroid volume as measured on ultrasound and antibody positivity. Complete thyroid workup was done in 106 patients of SSc which included thyroid function test, antithyroid peroxidase (TPO) antibody, antithyroid-stimulating hormone receptor (TSHR) antibody, antithyroglobulin antibody, and thyroid ultrasound to assess thyroid volume, echogenicity and blood flow, and fine needle aspiration cytology of suspicious thyroid lesions. Prevalence of subclinical hypothyroidism was 8.5 %, overt hypothyroidism 1.9 %, subclinical hyperthyroidism 2.8 %, and overt hyperthyroidism in 0.9 % of the patients. Antithyroid peroxidase antibody was positive in 16 %, anti-TSH receptor antibody in 5.7 %, and antithyroglobulin antibody in none of the patients. Thyroid volume was in the range of atrophy (<4.5 ml) in 57.5 % patients, echogenicity altered in 15.1 %, and blood flow increased in 15.1 %. Thyroid volume correlated strongly with the pulmonary function test (FEV1). Routine thyroid ultrasound and thyroid function tests may be included in the workup of patients with SSc for the early detection of hypothyroidism since a small but significant percentage of patients developed thyroid dysfunction. Antithyroid antibodies may not correlate with the thyroid functions and hence should not be recommended. PMID- 26861033 TI - Impact of the polymorphism in vitamin D receptor gene BsmI and the risk of systemic lupus erythematosus. PMID- 26861032 TI - Does vitamin D supplementation alleviate chronic nonspecific musculoskeletal pain? A systematic review and meta-analysis. AB - Chronic nonspecific musculoskeletal pain (CNMP) is an idiopathic condition often seen in general practice and rheumatology clinics, the aetiology of which may include vitamin D deficiency. The objective of the present study is to evaluate the effectiveness of vitamin D supplementation in the management of CNMP through a systematic review and meta-analysis. According to PRISMA guidelines, PubMed, Embase, Web of Science, Cochrane and Scopus electronic databases were searched for randomised controlled trials comparing vitamin D supplementation to a control or placebo in CNMP patients; the search was not limited by language or date. Meta analysis was performed using the mean and standardised mean difference which was computed with 95 % confidence intervals, and overall effect size was calculated. Both fixed and random effects models were used in meta-analysis to account for heterogeneity in the studies. The initial search identified 107 studies, of which 10 were potentially relevant, with 7 studies excluded because they did not meet selection criteria. Three studies were included in the meta-analysis. We found no effect of vitamin D supplementation (standardised mean difference (SMD) 0.004; 95 % confidence interval (CI) -0.248 to 0.256) on pain in CNMP patients. Forest plot is used to present the results from meta-analysis. Contrary to a widespread clinical view, there is a moderate level of evidence that vitamin D supplementation is not helpful for treating CNMP patients. PMID- 26861034 TI - Prediction of radiographic progression in synovitis-positive joints on maximum intensity projection of magnetic resonance imaging in rheumatoid arthritis. AB - Contrast-enhanced magnetic resonance imaging with maximum intensity projection (MRI-MIP) is an easy, useful imaging method to evaluate synovitis in rheumatoid hands. However, the prognosis of synovitis-positive joints on MRI-MIP has not been clarified. The aim of this study was to evaluate the relationship between synovitis visualized by MRI-MIP and joint destruction on X-rays in rheumatoid hands. The wrists, metacarpophalangeal (MP) joints, and proximal interphalangeal (PIP) joints of both hands (500 joints in total) were evaluated in 25 rheumatoid arthritis (RA) patients. Synovitis was scored from grade 0 to 2 on the MRI-MIP images. The Sharp/van der Heijde score and Larsen grade were used for radiographic evaluation. The relationships between the MIP score and the progression of radiographic scores and between the MIP score and bone marrow edema on MRI were analyzed using the trend test. As the MIP score increased, the Sharp/van der Heijde score and Larsen grade progressed severely. The rate of bone marrow edema-positive joints also increased with higher MIP scores. MRI-MIP imaging of RA hands is a clinically useful method that allows semi-quantitative evaluation of synovitis with ease and can be used to predict joint destruction. PMID- 26861035 TI - The prevalence of chondrocalcinosis of the symphysis pubis on CT scan and correlation with calcium pyrophosphate dihydrate crystal deposition disease. AB - Calcium pyrophosphate dihydrate (CPP) crystal deposition in the articular cartilage can often be seen radiographically as chondrocalcinosis (CC). CPP crystals preferentially deposit in fibrocartilages such as the knee menisci and symphysis pubis (SP). We sought to determine the prevalence of CC in the SP on computed tomography (CT) of the abdomen and pelvis. This retrospective study involved readings on 1070 consecutive CTs of the abdomen and pelvis performed over 3 months in patients over 65 years of age. Medical records of 226 patients found to have CC were reviewed to determine age, gender, documentation of CPPD on problem lists or in medical histories, and whether radiology readings of the CTs mentioned CC. SP CC was identified in 21.1 % (226/1070) of consecutive CT scans with the mean age of CT+ patients being 78.6. Of the 226 patients with SP CC, the observation of CC was documented in only 5.3 % (12/226) of the radiology reports. Of the 12 instances in which the radiology reports mentioned CC, this observation was never (0/12) transmitted to the medical history or problem list. The prevalence of SP CC in patients older than 65 was 21.1 %. Since the majority of CTs of the abdomen and pelvis are not ordered for evaluation of musculoskeletal conditions, this is likely a true prevalence without selection bias. When CC of the SP was present on images, radiologists routinely overlooked or chose not to report CC. Even in the rare instances when it was reported, that information was not added to the medical history or problem list. There are several clinical situations (e.g., acute monoarthritis or atypical osteoarthritis) in which recognizing that a patient has CPP deposition would be useful. Taking the time to review images may yield clinically important findings that are not mentioned anywhere on the patient chart. PMID- 26861037 TI - Henry Krum, Pioneering Heart Failure Researcher. PMID- 26861038 TI - February 2016 at a glance. Focus issue on cardiac regeneration, medical treatment and cardiac devices. PMID- 26861036 TI - The Relationship Between Greater Prepubertal Adiposity, Subsequent Age of Maturation, and Bone Strength During Adolescence. AB - This longitudinal study investigated whether greater prepubertal adiposity was associated with subsequent timing of maturation and bone strength during adolescence in 135 girls and 123 boys participating in the Iowa Bone Development Study. Greater adiposity was defined using body mass index (BMI) data at age 8 years to classify participants as overweight (OW, >=85th percentile for age and sex) or healthy weight (HW). Maturation was defined as the estimated age of peak height velocity (PHV) based on a series of cross-sectional estimates. Measurements were taken at ages 11, 13, 15, and 17 years for estimates of body composition by dual-energy X-ray absorptiometry (DXA), bone compression (bone strength index), and torsion strength (polar strength-strain index) at the radius and tibia by pQCT, and femoral neck bending strength (section modulus) by hip structural analysis. Bone strength in OW versus HW were evaluated by fitting sex specific linear mixed models that included centered age (visit age - grand mean age of cohort) as the time variable and adjusted for change in fat mass, and limb length in model 1. Analyses were repeated using biological age (visit age - age PHV) as the time variable for model 1 with additional adjustment for lean mass in model 2. BMI was negatively associated with age of maturation (p < 0.05). OW versus HW girls had significantly greater bone strength (p < 0.001) in model 1, whereas OW versus HW boys had significantly greater bone strength (p < 0.001) at the tibia and femoral neck but not radius (p > 0.05). Analyses were repeated using biological age, which yielded reduced parameter estimates for girls but similar results for boys (model 1.) Differences were no longer present after adjustment for lean mass (model 2) in girls (p > 0.05) whereas differences at the tibia were sustained in boys (p < 0.05). These findings demonstrate sex- and site specific differences in the associations between adiposity, maturation, and bone strength. (c) 2016 American Society for Bone and Mineral Research. PMID- 26861039 TI - Direct cellular reprogramming: the hopes and the hurdles. PMID- 26861040 TI - Corrigendum to 'What does the lay public know about heart failure? Findings from the Heart Failure Awareness Day Initiative'[Eur J Heart Fail 2016; 18:66-70]. AB - The published version of this paper contained an error. The part C of the figure only has the header "multiple organs", whereas it must read: "HF does not affect multiple organs". PMID- 26861041 TI - Analysis of X-ray absorption spectra of the K and L2,3 edges of GaN within the FP LAPW method. AB - Gallium nitride, GaN, is a semiconductor material with several technological applications. In this work we obtain ab initio XANES spectra using FP-LAPW method within the DFT formalism using different potentials (LDA, PBE and TB-mBJ) in order to study the electronic properties of the system. The spectra calculated using the effect of the fractional core hole were compared with experimental data obtaining a very good agreement. PMID- 26861042 TI - Cigarette and waterpipe smoking among adult patients with severe and persistent mental illness in Bahrain: a comparison with the National Non-communicable Diseases Risk Factors Survey. AB - BACKGROUND: Smoking has been associated with several types of mental illness namely schizophrenia, depression, bipolar disorders with a prevalence of smoking twice that of the general population. The study objective was to ascertain whether waterpipe tobacco smoking (WTS), cigarette smoking and all types of tobacco smoking are more common among Bahraini patients with severe and persistent mental illness (SPMI) than the general population. METHODS: A cross sectional study was conducted on 222 adult SPMI both in- and out- patients who attended the Psychiatric Hospital in Bahrain. A 29-item questionnaire, which included sociodemographic variables, pattern and history of psychiatric illness and a comprehensive smoking history, was used. Comparative smoking data were obtained from the Bahraini National Non-communicable Diseases Risk Factors Survey. RESULTS: The prevalence of smoking of tobacco among SPMI patients was 30.2 % compared to 19.9 % in the general population. The corresponding values for cigarette smoking were 25.2, 13.8 %, respectively and for WTS, 11.3, 8.4 %, respectively. SPMI patients were 1.7 (95 % CI 1.3, 2.4 %) times more likely to be smokers, 2.1 (95 % CI 1.5, 2.9 %) times, cigarette smokers and 1.4 (95 % CI 0.9, 1.9 %) times WTS than the general population. SPMI patients smoked at a younger age and consumed more cigarettes than the general population. The mean age started smoking was lower among men than women, similar for cigarettes, and higher for WTS. CONCLUSIONS: The prevalence of smoking among patients with SPMI in Bahrain is twice that of the general population. The findings of the study have implications on the provision of healthcare to mentally ill patients in the country. PMID- 26861043 TI - Phosphoproteomic analysis of interacting tumor and endothelial cells identifies regulatory mechanisms of transendothelial migration. AB - The exit of metastasizing tumor cells from the vasculature, extravasation, is regulated by their dynamic interactions with the endothelial cells that line the internal surface of vessels. To elucidate signals controlling tumor cell adhesion to the endothelium and subsequent transendothelial migration, we performed phosphoproteomic analysis to map cell-specific changes in protein phosphorylation that were triggered by contact between metastatic MDA-MB-231 breast cancer cells and endothelial cells. From the 2669 unique phosphorylation sites identified, 77 and 43 were differentially phosphorylated in the tumor cells and endothelial cells, respectively. The receptor tyrosine kinase ephrin type A receptor 2 (EPHA2) exhibited decreased Tyr(772) phosphorylation in the cancer cells upon endothelial contact. Knockdown of EPHA2 increased adhesion of the breast cancer cells to human umbilical vein endothelial cells (HUVECs) and their transendothelial migration in coculture cell assays, as well as early-stage lung colonization in vivo. EPHA2-mediated inhibition of transendothelial migration of breast cancer cells depended on interaction with the ligand ephrinA1 on HUVECs and phosphorylation of EPHA2-Tyr(772). When EPHA2 phosphorylation dynamics were compared between cell lines of different metastatic ability, EPHA2-Tyr(772) was rapidly dephosphorylated after ephrinA1 stimulation specifically in cells targeting the lung. Knockdown of the phosphatase LMW-PTP reduced adhesion and transendothelial migration of the breast cancer cells. Overall, cell-specific phosphoproteomic analysis provides a bidirectional map of contact-initiated signaling between tumor and endothelial cells that can be further investigated to identify mechanisms controlling the transendothelial cell migration of cancer cells. PMID- 26861044 TI - Plasma membrane localization of the MU-opioid receptor controls spatiotemporal signaling. AB - Differential regulation of the MU-opioid receptor (MOR), a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor, contributes to the clinically limiting effects of opioid analgesics, such as morphine. We used biophysical approaches to quantify spatiotemporal MOR signaling in response to different ligands. In human embryonic kidney (HEK) 293 cells overexpressing MOR, morphine caused a Gbetagamma-dependent increase in plasma membrane-localized protein kinase C (PKC) activity, which resulted in a restricted distribution of MOR within the plasma membrane and induced sustained cytosolic extracellular signal-regulated kinase (ERK) signaling. In contrast, the synthetic opioid peptide DAMGO ([d-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin) enabled receptor redistribution within the plasma membrane, resulting in transient increases in cytosolic and nuclear ERK activity, and, subsequently, receptor internalization. When Gbetagamma subunits or PKCalpha activity was inhibited or when the carboxyl terminal phosphorylation sites of MOR were mutated, morphine-activated MOR was released from its restricted plasma membrane localization and stimulated a transient increase in cytosolic and nuclear ERK activity in the absence of receptor internalization. Thus, these data suggest that the ligand-induced redistribution of MOR within the plasma membrane, and not its internalization, controls its spatiotemporal signaling. PMID- 26861045 TI - Toward total synthesis of cell function: Reconstituting cell dynamics with synthetic biology. AB - Biological phenomena, such as cellular differentiation and phagocytosis, are fundamental processes that enable cells to fulfill important physiological roles in multicellular organisms. In the field of synthetic biology, the study of these behaviors relies on the use of a broad range of molecular tools that enable the real-time manipulation and measurement of key components in the underlying signaling pathways. This Review will focus on a subset of synthetic biology tools known as bottom-up techniques, which use technologies such as optogenetics and chemically induced dimerization to reconstitute cellular behavior in cells. These techniques have been crucial not only in revealing causal relationships within signaling networks but also in identifying the minimal signaling components that are necessary for a given cellular function. We discuss studies that used these systems in a broad range of cellular and molecular phenomena, including the time dependent modulation of protein activity in cellular proliferation and differentiation, the reconstitution of phagocytosis, the reconstitution of chemotaxis, and the regulation of actin reorganization. Finally, we discuss the potential contribution of synthetic biology to medicine. PMID- 26861046 TI - Design of a mobile, homogeneous, and efficient electromagnet with a large field of view for neonatal low-field MRI. AB - OBJECTIVE: In this work, a prototype of an effective electromagnet with a field of-view (FoV) of 140 mm for neonatal head imaging is presented. The efficient implementation succeeded by exploiting the use of steel plates as a housing system. We achieved a compromise between large sample volumes, high homogeneity, high B0 field, low power consumption, light weight, simple fabrication, and conserved mobility without the necessity of a dedicated water cooling system. MATERIALS AND METHODS: The entire magnetic resonance imaging (MRI) system (electromagnet, gradient system, transmit/receive coil, control system) is introduced and its unique features discussed. Furthermore, simulations using a numerical optimization algorithm for magnet and gradient system are presented. RESULTS: Functionality and quality of this low-field scanner operating at 23 mT (generated with 500 W) is illustrated using spin-echo imaging (in-plane resolution 1.6 mm * 1.6 mm, slice thickness 5 mm, and signal-to-noise ratio (SNR) of 23 with a acquisition time of 29 min). B0 field-mapping measurements are presented to characterize the homogeneity of the magnet, and the B0 field limitations of 80 mT of the system are fully discussed. CONCLUSION: The cryogen free system presented here demonstrates that this electromagnet with a ferromagnetic housing can be optimized for MRI with an enhanced and homogeneous magnetic field. It offers an alternative to prepolarized MRI designs in both readout field strength and power use. There are multiple indications for the clinical medical application of such low-field devices. PMID- 26861047 TI - Correction of B 0-induced geometric distortion variations in prospective motion correction for 7T MRI. AB - OBJECTIVE: Prospective motion correction can effectively fix the imaging volume of interest. For large motion, this can lead to relative motion of coil sensitivities, distortions associated with imaging gradients and B 0 field variations. This work accounts for the B 0 field change due to subject movement, and proposes a method for correcting tissue magnetic susceptibility-related distortion in prospective motion correction. MATERIALS AND METHODS: The B 0 field shifts at the different head orientations were characterized. A volunteer performed large motion with prospective motion correction enabled. The acquired data were divided into multiple groups according to the object positions. The correction of B 0-related distortion was applied to each group of data individually via augmented sensitivity encoding with additionally integrated gradient nonlinearity correction. RESULTS: The relative motion of the gradients, B 0 field and coil sensitivities in prospective motion correction results in residual spatial distortion, blurring, and coil artifacts. These errors can be mitigated by the proposed method. Moreover, iterative conjugate gradient optimization with regularization provided superior results with smaller RMSE in comparison to standard conjugate gradient. CONCLUSION: The combined correction of B 0-related distortion and gradient nonlinearity leads to a reduction of residual motion artifacts in prospective motion correction data. PMID- 26861048 TI - Evaluating metabolites in patients with major depressive disorder who received mindfulness-based cognitive therapy and healthy controls using short echo MRSI at 7 Tesla. AB - OBJECTIVES: Our aim was to evaluate differences in metabolite levels between unmedicated patients with major depressive disorder (MDD) and healthy controls, to assess changes in metabolites in patients after they completed an 8-week course of mindfulness-based cognitive therapy (MBCT), and to exam the correlation between metabolites and depression severity. MATERIALS AND METHODS: Sixteen patients with MDD and ten age- and gender-matched healthy controls were studied using 3D short echo-time (20 ms) magnetic resonance spectroscopic imaging (MRSI) at 7 Tesla. Relative metabolite ratios were estimated in five regions of interest corresponding to insula, anterior cingulate cortex (ACC), caudate, putamen, and thalamus. RESULTS: In all cases, MBCT reduced severity of depression. The ratio of total choline-containing compounds/total creatine (tCr) in the right caudate was significantly increased compared to that in healthy controls, while ratios of N-acetyl aspartate (NAA)/tCr in the left ACC, myo-inositol/tCr in the right insula, and glutathione/tCr in the left putamen were significantly decreased. At baseline, the severity of depression was negatively correlated with my inositol/tCr in the left insula and putamen. The improvement in depression severity was significantly associated with changes in NAA/tCr in the left ACC. CONCLUSIONS: This study has successfully evaluated regional differences in metabolites for patients with MDD who received MBCT treatment and in controls using 7 Tesla MRSI. PMID- 26861050 TI - Heterodimerization of the Entamoeba histolytica EhCPADH virulence complex through molecular dynamics and protein-protein docking. AB - EhCPADH is a protein complex involved in the virulence of Entamoeba histolytica, the protozoan responsible for human amebiasis. It is formed by the EhCP112 cysteine protease and the EhADH adhesin. To explore the molecular basis of the complex formation, three-dimensional models were built for both proteins and molecular dynamics simulations (MDS) and docking calculations were performed. Results predicted that the pEhCP112 proenzyme and the mEhCP112 mature enzyme were globular and peripheral membrane proteins. Interestingly, in pEhCP112, the propeptide appeared hiding the catalytic site (C167, H329, N348); while in mEhCP112, this site was exposed and its residues were found structurally closer than in pEhCP112. EhADH emerged as an extended peripheral membrane protein with high fluctuation in Bro1 and V shape domains. 500 ns-long MDS and protein-protein docking predictions evidenced different heterodimeric complexes with the lowest free energy. pEhCP112 interacted with EhADH by the propeptide and C-terminal regions and mEhCP112 by the C-terminal through hydrogen bonds. In contrast, EhADH bound to mEhCP112 by 442-479 residues, adjacent to the target cell-adherence region (480-600 residues), and by the Bro1 domain (9-349 residues). Calculations of the effective binding free energy and per residue free energy decomposition showed that EhADH binds to mEhCP112 with a higher binding energy than to pEhCP112, mainly through van der Waals interactions and the nonpolar part of solvation energy. The EhADH and EhCP112 structural relationship was validated in trophozoites by immunofluorescence, TEM, and immunoprecipitation assays. Experimental findings fair agreed with in silico results. PMID- 26861049 TI - Subjective perception of safety in healthy individuals working with 7 T MRI scanners: a retrospective multicenter survey. AB - OBJECTIVE: To retrospectively assess perception of safety of healthy individuals working with human 7 Tesla (T) magnetic resonance imaging (MRI) scanners. MATERIALS AND METHODS: A total of 66 healthy individuals with a mean age of 31 +/ 7 years participated in this retrospective multicentre survey study. Nonparametric correlation analysis was conducted to evaluate the relation between self-reported perception of safety and prevalence of sensory effects while working with 7 T MRI scanners for an average 47 months. RESULTS: The results indicated that 98.5 % of the study participants had a neutral or positive feeling about safety aspects at 7 T MRI scanners. 45.5 % reported that they feel very safe and none of the participants stated that they feel moderately or very unsafe while working with 7 T MRI scanners. Perception of safety was not affected by the number of hours per week spent in the vicinity of the 7 T MRI scanner or the duration of experience with 7 T MRI. More than 50 % of individuals experienced vertigo and metallic taste while working with 7 T MRI scanners. However, participants' perceptions of safety were not affected by the prevalence of MR related symptoms. CONCLUSIONS: The overall data indicated an average perception of a moderately safe work environment. To our knowledge, this study delineates the first attempt to assess the subjective safety perception among 7 T MRI workers and suggests further investigations are indicated. PMID- 26861051 TI - Once-daily mesalamine granules for maintaining remission of ulcerative colitis: pooled analysis of efficacy, safety, and prognostic factors. AB - OBJECTIVES: A capsule formulation of mesalamine granules (MG) was developed for once-daily dosing and better compliance. The study aim was to evaluate MG efficacy and tolerability in maintaining ulcerative colitis (UC) remission. METHODS: Pooled analysis of 2 identical phase 3, randomized, double-blind trials of once-daily MG 1.5 g or placebo for up to 6 months. The primary endpoint was percentage of patients remaining relapse-free at month 6 versus placebo. Relapse was defined as revised Sutherland Disease Activity Index (SDAI) rectal bleeding score >=1 and mucosal appearance score >=2, UC flare, or UC-related adverse event (AE). RESULTS: Data were pooled for patients receiving MG (n = 373) and placebo (n = 189). Significantly more patients were relapse-free at 6 months with MG (79.4%) than placebo (62.4%; P < 0.001) and across subgroups based on select demographic and baseline characteristics (P < 0.05). Secondary outcome measures including rectal bleeding, physician rating of disease activity, stool frequency, total SDAI score, and relapse-free duration favored MG (P < 0.01). Common AEs with MG and placebo, respectively, were headache (10.9% and 7.6%), diarrhea (7.9% and 7.0%), and abdominal pain (6.3% and 6.5%). CONCLUSION: Once-daily MG was more efficacious than and as well tolerated as placebo in maintaining UC remission. ClinicalTrials.gov identifiers: NCT00744016 and NCT00767728. PMID- 26861052 TI - Relevance of spontaneous fabT mutations to a streptococcal toxic shock syndrome to non-streptococcal toxic shock syndrome transition in the novel-type Streptococcus pyogenes isolates that lost a salRK. AB - Streptococcus pyogenes is a causative agent of streptococcal toxic shock syndrome (STSS). Mutations in covR/S or rgg, negative regulators, can reportedly modulate the severity of infection in this pathogen. Recently, we showed that the regions encoding the SalR-SalK, a two-component regulatory system, were deleted in some emm 1-type isolates (named as 'novel-type'). In this study, the two novel 'STSS' isolates 10-85stss and 11-171stss were more virulent than the two novel 'non STSS' isolates 11O-2non and 11T-3non when examined using a mouse model of invasive infection. Genome-sequencing experiments using the three strains 10 85stss , 11-171stss , and 11O-2non detected only one single nucleotide polymorphism that causes a non-synonymous mutation in fabT encoding a transcriptional regulator in strain 11O-2non . Loss of fabT reduced the high level of virulence observed in the STSS isolates to that in the non-STSS isolates, and introduction of an intact fabT compensated the lower virulence of 11O-2non , suggesting that the mutation in fabT, but not in covR/S or rgg, is involved in the differential virulence among the novel-type clinical isolates. This type of non-synonymous fabT mutation was also identified in 12 non-STSS isolates (including 11O-2non and 11T-3non ), and most of those 12 isolates showed impaired FabT function. PMID- 26861053 TI - Memory complaints in subjective cognitive impairment, amnestic mild cognitive impairment and mild Alzheimer's disease. AB - Memory complaints are a frequent phenomenon in elderly individuals and can lead to opportunistic help-seeking behavior. The aim of this study was to compare different aspects of memory complaints (i.e., prospective versus retrospective complaints) in individuals with subjective cognitive impairment (SCI), amnestic mild cognitive impairment (aMCI), and mild Alzheimer's disease (AD). The study included a total of 115 participants (mean age: 68.82 +/- 8.83 years) with SCI (n = 34), aMCI (n = 46), and mild AD (n = 35). Memory complaints were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), which consists of 16 items that describe everyday memory failure of both prospective memory (PM) and retrospective memory (RM). For aMCI and AD subjects, informants also completed an informant-rating of the PRMQ. All participants completed detailed neuropsychological tests. Results show that PM complaints were equivalent among the three groups. However, RM complaints differed. Specifically, RM complaints in aMCI were higher than SCI, but similar to AD. Informant-reported memory complaints were higher for AD than aMCI. Our study suggests that RM complaints of memory complaints may be helpful in discriminating between SCI and aMCI, but both PM and RM complaints are of limited value in differentiating aMCI from AD. PMID- 26861054 TI - Alteration of phospholipids in the blood of patients with Duchenne muscular dystrophy (DMD): in vitro, high resolution 31P NMR-based study. AB - In vitro, high-resolution 31P NMR (Nuclear Magnetic Resonance) spectroscopy-based analysis of phospholipids in serum is well recognized in leukemia, lymphoma, non hematological cancers and renal cell carcinoma. In context of these studies, phospholipids were analyzed in blood of thirty-two (n = 32) patients with Duchenne muscular dystrophy (DMD) (Age, Mean +/- SD; 8.0 +/- 1.6 years) and sixteen (n = 16) healthy subjects (Age, Mean +/- SD; 8.6 +/- 2.3 years). Quantity of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS) and lyso-phosphatidylcholine (Lys-PC) was significantly higher (p < 0.05) in DMD patients as compared to healthy subjects. There were no significant differences (p > 0.05) observed for the quantity of phospholipids in blood of gene deletion positive cases of DMD as compared to negative gene deletion cases of DMD. Quantity of phospholipids in negative gene deletion cases of DMD patients as well as DMD cases with positive gene deletion was significantly higher (p < 0.05) as compared to normal individuals. The present study distinguishes the patients with DMD from the healthy subjects on the basis of the quantity of phospholipids in blood. These observations may be useful in future for the development of new diagnostic method of DMD. PMID- 26861055 TI - Inulin-type fructan fermentation by bifidobacteria depends on the strain rather than the species and region in the human intestine. AB - Inulin-type fructans (ITF) are known to cause a health-promoting bifidogenic effect, although the ITF degradation capacity of bifidobacteria in different intestinal regions remains unclear. The present study aims at offering new insights into this link, making use of a collection of 190 bifidobacterial strains, encompassing strains from gut biopsies (terminal ileum and proximal colon; mucosa-associated strains) and the simulator of the human intestinal microbial ecosystem (SHIME(r); proximal and distal colon vessels; lumen associated strains). A multivariate data analysis of all fermentation data revealed four clusters corresponding with different types of ITF degradation fingerprints, which were not correlated with the region in the intestine, suggesting that the degradation of ITF is uniform along the human intestine. Strains from cluster 1 consumed fructose, while strains from cluster 2 consumed more oligofructose than fructose. Higher fructose and oligofructose consumption was characteristic for clusters 3 and 4 strains, which degraded inulin too. In general, the mucosa-associated strains from biopsy origin seemed to be more specialized in the consumption of fructose and oligofructose, while the lumen associated strains from SHIME origin displayed a higher degradation degree of inulin. Further, intra-species variability in ITF degradation was found, indicating strain-specific variations. The coexistence of different bifidobacterial strains with different ITF degradation fingerprints within the same intestinal region suggests cooperation for the degradation of ITF, with opportunities for cross-feeding on strain and/or species level. PMID- 26861056 TI - Impact of very low physical activity, BMI, and comorbidities on mortality among breast cancer survivors. AB - The purpose of this study was to examine post-diagnosis BMI, very low physical activity, and comorbidities, as predictors of breast cancer-specific and all cause mortality. Data from three female US breast cancer survivor cohorts were harmonized in the After Breast Cancer Pooling Project (n = 9513). Delayed entry Cox proportional hazards models were used to examine the impact of three post diagnosis lifestyle factors: body mass index (BMI), select comorbidities (diabetes only, hypertension only, or both), and very low physical activity (defined as physical activity <1.5 MET h/week) in individual models and together in multivariate models for breast cancer and all-cause mortality. For breast cancer mortality, the individual lifestyle models demonstrated a significant association with very low physical activity but not with the selected comorbidities or BMI. In the model that included all three lifestyle variables, very low physical activity was associated with a 22 % increased risk of breast cancer mortality (HR 1.22, 95 % CI 1.05, 1.42). For all-cause mortality, the three individual models demonstrated significant associations for all three lifestyle predictors. In the combined model, the strength and significance of the association of comorbidities (both hypertension and diabetes versus neither: HR 2.16, 95 % CI 1.79, 2.60) and very low physical activity (HR 1.35, 95 % CI 1.22, 1.51) remained unchanged, but the association with obesity was completely attenuated. These data indicate that after active treatment, very low physical activity, consistent with a sedentary lifestyle (and comorbidities for all-cause mortality), may account for the increased risk of mortality, with higher BMI, that is seen in other studies. PMID- 26861057 TI - Biological Activity of Japanese Quince Extract and Its Interactions with Lipids, Erythrocyte Membrane, and Human Albumin. AB - The aim of the study was to determine in vitro biological activity of fruit ethanol extract from Chaenomeles speciosa (Sweet) Nakai (Japanese quince, JQ) and its important constituents (-)-epicatechin (EC) and chlorogenic acid (CA). The study also investigated the structural changes in phosphatidylcholine (PC) liposomes, dipalmitoylphosphatidylcholine liposomes, and erythrocyte membranes (RBC) induced by the extract. It was found that the extract effectively inhibits oxidation of RBC, induced by 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), and PC liposomes, induced by UVB radiation and AAPH. Furthermore, JQ extract to a significant degree inhibited the activity of the enzymes COX-1 and COX-2, involved in inflammatory reactions. The extract has more than 2 times greater activity in relation to COX-2 than COX-1 (selectivity ratio 0.48). JQ extract stimulated growth of the beneficial intestinal bacteria Lactobacillus casei and Lactobacillus plantarum. In the fluorimetric method by means of the probes Laurdan, DPH and TMA-DPH, and (1)H-NMR, we examined the structural changes induced by JQ and its EC and CA components. The results show that JQ and its components induce a considerable increase of the packing order of the polar heads of lipids with a slight decrease in mobility of the acyl chains. Lipid membrane rigidification could hinder the diffusion of free radicals, resulting in inhibition of oxidative damage induced by physicochemical agents. JQ extract has the ability to quench the intrinsic fluorescence of human serum albumin through static quenching. This report thus could be of huge significance in the food industry, pharmacology, and clinical medicine. PMID- 26861058 TI - Mammographic breast density in infertile and parous women. AB - BACKGROUND: Mammographic breast density is a useful marker for breast cancer risk, as breast density is considered one of the strongest breast cancer risk factors. The study objective was to evaluate and compare mammographic breast density in infertile and parous women, as infertility may be associated with high breast density and cancer occurrence. METHODS: This study evaluated mammographic breast density using two different systems, BIRADS and Boyd. A selected patient population of 151 women with primary infertility (case group) was compared to 154 parous women who had at least one previous pregnancy (control group). Both groups were premenopausal women aged >= 35. RESULTS: Evaluation of mammographic features showed that 66.9% of case group patients and 53.9% of control group patients were classified BIRADS-3/BIRADS-4; p < 0.05. Adjusted Odds ratio for the case group in the categories BIRADS-3/BIRADS-4 was 1.78 (95% CI: 1.10-2.89). Using the Boyd classification system, 53.6% of case group patients and 31.8% of control group patients were classified E/F; p < 0.05. Adjusted Odds ratio for case group patients in Boyd categories E/F was 2.05 (95 % CI: 1.07-3.93). CONCLUSIONS: Both systems yielded a higher percentage of increased breast density in the case group. Boyd and BIRADS classification systems indicate to what extend breast cancer lesions may be missed on mammography due to masking by dense tissue. Therefore, patients with a high BIRADS or Boyd score should undergo further investigation. PMID- 26861059 TI - Pancreatic duct hyperplasia/dysplasia in type 1 diabetes and pancreatic weight in individuals with and without diabetes. Reply to Kobayashi T, Aida K, Fukui T et al [letter] and Saisho Y [letter]. PMID- 26861060 TI - Uremia-caused changes of ghrelin system in hippocampus may be associated with impaired cognitive function of hippocampus. AB - PURPOSE: Hippocampus plays an important role in spatial learning and memory. Ghrelin, a brain-gut peptide, participates in the mnestic functions of hippocampus through its receptor growth hormone secretagogue receptor (GHS-R) distributed in hippocampus. This study was to investigate whether there was a correlation between the changes of ghrelin system in hippocampus and the spatial cognitive impairment caused by chronic renal failure (CRF). METHODS: Sprague Dawley rats (male, 180 +/- 10 g, 7-8 weeks old) were randomly classified into CRF group and control group (n = 18 per group). The CRF model was constructed by 5/6 nephrectomy and the controls treated with sham operation. By the 8th week after the surgery, the spatial cognitive function of rats was assessed by Morris water maze test (MWM), the protein expression of ghrelin and GHS-R in the hippocampus by immunohistochemistry, and the mRNA expression by real-time PCR. Statistical analysis was performed using ANOVA, Student-Newman-Keuls-q test and Pearson correlation analysis, and P < 0.05 was considered significant. RESULTS: Compared with the controls, the time spent in "platform" quadrant (TSPQ) of rats with CRF was decreased, but the escape latency (EL) was increased significantly in MWM, and meanwhile the protein and mRNA expression of ghrelin and GHS-R in hippocampus was also increased significantly (P < 0.05 or P < 0.01). Correlation analysis suggested that the TSPQ was negatively but the EL was positively correlated with the mRNA expression of ghrelin and GHS-R (P < 0.01). CONCLUSION: The CRF-caused changes of ghrelin system in hippocampus might be correlated with the CRF-caused cognitive function impairment. PMID- 26861061 TI - Inhibiting malignant phenotypes of the bladder cancer cells by silencing long noncoding RNA SChLAP1. AB - BACKGROUND AND OBJECTIVES: Long noncoding RNAs (lncRNAs) play key roles in process of cancer cell growth and apoptosis and have received increasing attention. SChLAP1 is a novel lncRNA that is required for development and progression of prostate cancer. We hypothesized that SChLAP1 also has important biological functions in human bladder cancer which is another type of urological cancer. METHODS: The expression of SChLAP1 in bladder cancer was determined using real-time qPCR. Bladder cancer T24 and 5637 cells were transfected with SChLAP1 siRNA or negative control siRNA. Cell proliferation, apoptosis and migration were determined using CCK-8 assay, flow cytometry analysis and wound healing assay, respectively. RESULTS: SChLAP1 was overexpressed in bladder cancer tissues compared to paired normal bladder tissues. Cell growth arrest, apoptosis induction and migration inhibition were also observed in bladder cancer T24 and 5637 cells after transfection with SChLAP1 siRNA. CONCLUSIONS: Our data suggest that SChLAP1 plays oncogenic roles and can be used as a therapeutic target for treating human bladder cancer. PMID- 26861062 TI - Oncological outcomes and prognostic factors after nephron-sparing surgery in renal cell carcinoma. AB - PURPOSE: To analyse the mid-term oncological results and to asses predictive factors for recurrence and survival after nephron-sparing surgery (NSS) for renal cell carcinoma. MATERIALS AND METHODS: This is a retrospective study that includes 198 Partial Nephrectomies performed at our institution for malignant renal tumours. Demographic information and pathological characteristics were obtained, and completed statistical analysis was performed to assess predictors for overall survival (OS) and overall recurrence in our sample. RESULTS: The presence of positive surgical margins (PSM) in the surgical specimen was reported in 13.6 %. At a median of follow-up of 56.1 months, the non-adjusted cancer specific mortality, DSS and OS were 100, and 93.4 %, respectively. In the bivariate analysis regarding predictive factors for recurrence, bilaterality and NSS indication (elective or imperative) were statistically significant (p = 0.03 and p = 0.05 respectively). On multivariate analysis only bilaterality was a significant predictor of recurrence (p = 0.03), while high Fuhrman grade was for survival (p = 0.006). CONCLUSION: Our data suggest that patients with bilateral tumours have a higher incidence of local recurrence. Regarding overall survival, our data showed more risk of death at 5 years in those patients with high Fuhrman grade. No differences were found among PSM and negative surgical margins patients regarding oncological outcomes. PMID- 26861063 TI - Prognostic value of cytoreductive nephrectomy combined with targeted therapy for metastatic renal cell carcinoma: a meta-analysis. AB - PURPOSE: The role of cytoreductive nephrectomy (CN) has been controversial with the advent of targeted therapy. Our study was to identify the prognostic value of CN combined with targeted therapy for treatment of metastatic renal cell carcinoma (mRCC) by conducting a meta-analysis based on the existing population based studies. METHODS: Research articles published up to September 2015 were searched through PubMed and Embase. A meta-analysis was performed to assess the overall survival (OS) and progression-free survival (PFS) of patients with mRCC undergoing CN combined with targeted therapy compared with targeted therapy alone. Furthermore, analysis was made to evaluate some potential prognostic factors predicting survival. RESULTS: Eight studies were included in our analysis with 2688 mRCC patients. A fixed-effect model was performed and found the pooled HR of OS was 0.60 (95 % CI 0.53-0.67, p < 0.0001). Furthermore, the pooled median survival ratio was elevated (HR 2.11, 95 % CI 1.78-2.49, p < 0.0001), indicating that patients who received CN combined with targeted therapy yielded a more than twofold prolonged OS compared with those who received targeted therapy alone. Moreover, no significant difference was observed in PFS in the patients undergoing CN combined with targeted therapy (HR 0.82, 95 % CI 0.57-1.19, p = 0.30). CONCLUSIONS: Current evidence suggests that CN combined with targeted therapy has a significant OS advantage in patients with mRCC. However, the results should be evaluated in the context of the potential selection biases of the existing evidence. Large prospective cohort studies are required to confirm these findings. PMID- 26861064 TI - Active malignancy in patients with renal vein thrombosis: influence upon clinical course and survival. AB - BACKGROUND: Renal vein thrombosis (RVT) is a rare event with myriad clinical manifestations. Published experience regarding the clinical course and management of RVT in patients beyond the neonatal period is limited to case reports and small case series. METHODS: A multicenter retrospective review of consecutive admitted patients with diagnosed RVT between January 2000 and May 2015 at three different university hospitals. RESULTS: Thirty-nine patients (53.8 % men and 46.2 % women) were included. Median age was 58 years. Malignancy (n = 19, 48.7 %), nephrotic syndrome (n = 8, 20.5 %) and infection (n = 5, 12.8 %), were the most common underlying conditions. Compared to non-cancer patients, patients with active cancer tended to be significantly older (mean age 63 +/- 18 vs. 37 +/- 22 years, P = 0.001) and presented with non-acute symptoms (P = 0.01) and unrevealing physical findings (P = 0.02). Thrombosis extension beyond the renal vein occurred in 69.2 % of cases and was more common in cancer patients (P = 0.001). Anticoagulation therapy was administered in 71.8 % of patients leading to resolution of thrombus in most cases (30/32 patients, 94 %) during follow-up evaluation. There were six recurrent thrombotic events during a mean follow-up of 35 +/- 43 months. Nine patients (28 %) died during follow-up, all of them with malignancy. CONCLUSION: Active cancer is the most common cause of RVT and should be excluded when RVT is diagnosed. Clinical course of RVT in cancer patients is more indolent and diagnosis requires high index of suspicion. Survival rates are governed by the presence of malignancy. PMID- 26861066 TI - Completeness of serious adverse drug event reports received by the US Food and Drug Administration in 2014. AB - PURPOSE: Adverse drug event reports to the US Food and Drug Administration (FDA) remain the primary tool for identifying serious drug adverse effects without adequate existing warnings. We assessed the completeness of reports the FDA received in 2014. METHODS: Serious adverse drug event reports were evaluated for whether they included age, gender, event date, and at least one medical term describing the event in computer excerpts. Report sources were direct reports to the FDA, manufacturer expedited reports about events without adequate warnings, and manufacturer periodic reports about events with existing warnings. RESULTS: In 2014, the FDA received 528,192 new case reports indicating a serious or fatal outcome, 25,038 (4.7%) directly from health professionals and consumers, and 503,154 (95.3%) from drug manufacturers. Overall, 21,595 (86.2%) of serious reports submitted directly to the FDA provided data for all four completeness variables, compared with 271,022 (40.4%) of manufacturer expedited reports and 24,988 (51.3%) of periodic reports. Among manufacturer serious reports, 37.9% lacked age and 46.9% had no event date. Performance by 25 manufacturers submitting 5000 or more reports varied from 24.4% complete on all variables to 67% complete. Patient death cases had the lowest completeness scores in all categories. CONCLUSIONS: By these measures, report completeness from drug manufacturers was poor compared with direct submissions to the agency. The FDA needs to update reporting requirements and compliance policies to help industry capture better adverse event information from new forms of manufacturer interactions with health professionals and consumers. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26861065 TI - The CYLD p.R758X worldwide recurrent nonsense mutation detected in patients with multiple familial trichoepithelioma type 1, Brooke-Spiegler syndrome and familial cylindromatosis represents a mutational hotspot in the gene. AB - BACKGROUND: Multiple familial trichoepithelioma type 1 (MFT1; MIM 601606), a rare monogenic skin disease with autosomal dominant inheritance, is characterized by the development of multiple skin-colored papules on the central area of the face, frequently occurring in the nasolabial area. The disease is associated with various mutations in the cylindromatosis (CYLD; MIM 605018) gene that are also responsible for familial cylindromatosis (FC) and Brooke-Spiegler syndrome (BSS). METHODS: Recently we have identified a Spanish MFT1 pedigree with two affected family members (father and daughter). Direct sequencing of the CYLD gene revealed a worldwide recurrent heterozygous nonsense mutation (c.2272C/T, p.R758X) in the patients. RESULTS: This mutation has already been detected in patients with all three clinical variants - BSS, FC and MFT1 - of the CYLD-mutation spectrum. Haplotype analysis was performed for the Spanish patients with MFT1, Dutch patients with FC and an Austrian patient with BSS, all of whom carry the same heterozygous nonsense p.R758X CYLD mutation. CONCLUSIONS: Our results indicate that this position is a mutational hotspot on the gene and that patients carrying the mutation exhibit high phenotypic diversity. PMID- 26861067 TI - A look into the future of ALS research. AB - Although amyotrophic lateral sclerosis (ALS), also referred as 'Lou Gehrig's Disease,' was first described in 1869 and the first disease-associated gene was discovered almost 20 years ago, the disease etiology is still not fully understood and treatment options are limited to one drug approved by the US Food and Drug Administration (FDA). The slow translational progress suggests that current research models are not ideal to study such a complicated disease and need to be re-examined. Progress will require greater insight into human genes and biology involved in ALS susceptibility, as well as a deeper understanding of disease phenotype at the histological and molecular levels. Improving human disease outcome will require directing focus toward improved assessment technologies and innovative approaches. PMID- 26861068 TI - Sampling method evaluation and empirical model fitting for count data to estimate densities of Oligonychus perseae (Acari: Tetranychidae) on 'Hass' avocado leaves in southern California. AB - Oligonychus perseae (Acari: Tetranychidae) is an important foliar spider mite pest of 'Hass' avocados in several commercial production areas of the world. In California (USA), O. perseae densities in orchards can exceed more than 100 mites per leaf and this makes enumerative counting prohibitive for field sampling. In this study, partial enumerative mite counts along half a vein on an avocado leaf, an industry recommended practice known as the "half-vein method", was evaluated for accuracy using four data sets with a combined total of more than 485,913 motile O. perseae counted on 3849 leaves. Sampling simulations indicated that the half-vein method underestimated mite densities in a range of 15-60 %. This problem may adversely affect management of this pest in orchards and potentially compromise the results of field research requiring accurate mite density estimation. To address this limitation, four negative binomial regression models were fit to count data in an attempt to rescue the half-vein method for estimating mite densities. These models were incorporated into sampling plans and evaluated for their ability to estimate mite densities on whole leaves within 30 tree blocks of avocados. Model 3, a revised version of the original half-vein model, showed improvement in providing reliable estimates of O. perseae densities for making assessments of general leaf infestation densities across orchards in southern California. The implications of these results for customizing the revised half-vein method as a potential field sampling tool and for experimental research in avocado production in California are discussed. PMID- 26861069 TI - Community structure variability of Uropodina mites (Acari: Mesostigmata) in nests of the common mole, Talpa europaea, in Central Europe. AB - Underground nests of Talpa europaea, known as the common mole, are very specific microhabitats, which are also quite often inhabited by various groups of arthropods. Mites from the suborder Uropodina (Acari: Mesostigmata) are only one of them. One could expect that mole nests that are closely located are inhabited by communities of arthropods with similar species composition and structure. However, results of empirical studies clearly show that even nests which are close to each other can be different both in terms of the species composition and abundance of Uropodina communities. So far, little is known about the factors that can cause these differences. The major aim of this study was to identify factors determining species composition, abundance, and community structure of Uropodina communities in mole nests. The study is based on material collected during a long-term investigation conducted in western parts of Poland. The results indicate that the two most important factors influencing species composition and abundance of Uropodina communities in mole nests are nest building material and depth at which nests are located. Composition of Uropodina communities in nests of moles was also compared with that of other microhabitats (e.g. rotten wood, forest litter, soil) based on data from 4421 samples collected in Poland. Communities of this habitat prove most similar to these of open areas, especially meadows, as well as some forest types. PMID- 26861070 TI - Resuscitative endovascular balloon occlusion of the aorta for uncontrolled haemorrahgic shock as an adjunct to haemostatic procedures in the acute care setting. AB - BACKGROUND: Haemorrhagic shock is a major cause of death in the acute care setting. Since 2009, our emergency department has used intra-aortic balloon occlusion (IABO) catheters for resuscitative endovascular balloon occlusion of the aorta (REBOA). METHODS: REBOA procedures were performed by one or two trained acute care physicians in the emergency room (ER) and intensive care unit (ICU). IABO catheters were positioned using ultrasonography. Collected data included clinical characteristics, haemorrhagic severity, blood cultures, metabolic values, blood transfusions, REBOA-related complications and mortality. RESULTS: Subjects comprised 25 patients (trauma, n = 16; non-trauma, n = 9) with a median age of 69 years and a median shock index of 1.4. REBOA was achieved in 22 patients, but failed in three elderly trauma patients. Systolic blood pressure significantly increased after REBOA (107 vs. 71 mmHg, p < 0.01). Five trauma patients (20 %) died in ER, and mortality rates within 24 h and 60 days were 20 % and 12 %, respectively. No REBOA-related complications were encountered. The total occlusion time of REBOA was significantly lesser in survivors than that in non-survivors (52 vs. 97 min, p < 0.01). Significantly positive correlations were found between total occlusion time of REBOA and shock index (Spearman's r = 0.6) and lactate concentration (Spearman's r = 0.7) in survivors. CONCLUSION: REBOA can be performed in ER and ICU with a high degree of technical success. Furthermore, correlations between occlusion time and initial high lactate levels and shock index may be important because prolonged occlusion is associated with a poorer outcome. PMID- 26861071 TI - About my Child: measuring 'Complexity' in neurodisability. Evidence of reliability and validity. AB - BACKGROUND: About my Child, 26-item version (AMC-26) was developed as a measure of child health 'complexity' and has been proposed as a tool for understanding the functional needs of children and the priorities of families. METHODS: The current study investigated the reliability and validity of AMC-26 with a sample of caregivers of children with neurodevelopmental disorders (NDD; n = 258) who completed AMC-26 as part of a larger study on parenting children with NDD. A subsample of children from the larger study (n = 49) were assessed using standardized measures of cognitive and adaptive functioning. RESULTS: Factor analysis revealed that a four-component model explained 51.12% of the variance. Cronbach's alpha was calculated for each of the four factors and for the scale as a whole, and ranged from 0.75 to 0.85, suggesting a high level of internal consistency. Construct validity was tested through comparisons with the results of standardized measures of child functioning. Predicted relationships for factors one, two and three were statistically significant and in the expected directions. Predictions for factor four were partially supported. AMC-26 was also expected to serve as an indicator of caregiver distress. Drawing on a sample of caregivers from the larger study (n = 251) the model was found to be significant and explained 23% of the variance in caregiver depressive symptoms (R(2) = .053, F (1, 249) = 14.06, P < .001). CONCLUSIONS: Based on these observations, the authors contend that AMC-26 may be used by clinicians and researchers as a tool to capture child function and child health complexity. Such a measure may help elucidate the relationships between child complexity and family well-being. This is an important avenue for further investigation. PMID- 26861073 TI - Procalcitonin cannot be used as a biomarker of infection in heart surgery patients with acute kidney injury. AB - PURPOSE: We intended to assess how acute kidney injuy impacts on procalcitonin levels in cardiac surgery patients, with or without infection, and whether procalcitonin might be used as a biomarker of infection in acute kidney injuy. MATERIAL AND METHODS: A case-control study was designed which included patients that had had cardiac surgery between January 2011 and January 2015. Every patient developing severe sepsis or septic shock (n = 122; 5.5%) was enrolled. In addition, consecutive cardiac surgery patients during 2013 developing systemic inflammatory response syndrome (n = 318) were enrolled. Those recruited 440 patients were divided into 2 groups, according to renal function. RESULTS: Median procalcitonin levels were significantly higher during the 10 postoperative days in the acute kidney injury patients. Regression analysis showed that postoperatory day, creatinine, white blood cells and infection were significantly (P < .0001) associated to serum procalcitonin level. In patients with creatinine >=2, median procalcitonin levels were similar in infected and non-infected patients. Only when creatinine was less than 2 mg/L, the median procalcitonin levels were significantly higher in patients with infection, as compared to those with no infection. CONCLUSIONS: In acute kidney injuy patients, high procalcitonin levels are a marker of acute kidney injuy but will not be able to differentiate infected from non-infected patients. PMID- 26861072 TI - A prospective observational study of CYP2C19 polymorphisms and voriconazole plasma level in adult Thai patients with invasive aspergillosis. AB - The aim of this study was to investigate the association of genetic variants of CYP2C19 (CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles) and voriconazole trough plasma concentrations in Thai patients with invasive fungal infection. A total of 285 samples from patients with invasive fungal infection and treated with voriconazole were prospectively enrolled. At steady state, trough voriconazole concentrations were measured using tandem mass spectrophotometry and high performance liquid chromatography. The genetic variants in the CYP2C19 gene were genotyped for CYP2C19*2 (G681A), CYP2C19*3 (G636A) and CYP2C19*17 (C-806T) on plasma voriconazole level. Voriconazole Ctrough levels were positively associated with CYP2C19*3. The median Ctrough level for patients with the 636GA genotype (2.109, IQR 1.054-4.166 MUg/ml) was statistically significantly higher than those with the 636GG genotype (1.596, IQR 0.755-2.980 MUg/ml), P = 0.046. The patients with a poor metabolizer (PM; CYP2C19*2/*2, *2/*3) had voriconazole Ctrough level of 1.900 (IQR, 1.130-3.673 MUg/ml). This was statistically significantly higher than that seen with the extensive metabolizer phenotype (1.470; IQR, 0.632-2.720 MUg/ml), P = 0.039. An association between CYP2C19 variant alleles and high voriconazole plasma level was identified. Therefore, determining the CYP2C19 genotype before initiation of voriconazole treatment may be useful in optimizing the dosing regimen in Thai patients with invasive fungal infections. PMID- 26861074 TI - Global transcriptional expression in ovarian follicles from Tsaiya ducks (Anas platyrhynchos) with a high-fertilization rate. AB - Novel candidates for biomarkers of a high-fertilization rate were identified here through global transcriptional profiling of ovarian follicles. Some other differentially expressed candidate genes were first noted to influence animal reproduction in our previous cDNA microarray analysis and are now recognized as markers for marker-assisted selection. In the present study, we compared gene expression in ovarian follicles from animals with high- and low-fertilization rates using an oligonucleotide array. On the basis of a fold change of greater than 1.2 and less than -1.2, a difference of >100 Affymetrix arbitrary units between the two groups, and a P value of less than 0.05, 47 genes were found to be associated with fertilization rate. GOEAST and MetaCore software were further used to identify the functional categories of genes that were differentially expressed. Then, we focused on three interesting genes associated with a high fertilization rate: one of these genes was discovered to participate in signaling pathways of fertilization, and two genes take roles in lipid metabolism. An oligonucleotide array showed that the levels of orthodenticle homeobox 2 (OTX2) and lecithin:cholesterol acyltransferase (LCAT) gene expression were 1.62-fold and 1.95-fold higher in the high-fertilization rate group than in the low fertilization rate group, respectively (P < 0.05). The level of apolipoprotein A I (APOA1) gene expression was also higher in the high-fertilization rate group, with a difference of 2.31-fold (P < 0.05). The data were validated through quantitative polymerase chain reaction analysis. These results confirm the usefulness of the array technique and data mining methods in the discovery of new biomarkers and add knowledge to our understanding of the factors affecting fertilization rates in ovarian follicles. PMID- 26861076 TI - Exponential Sensitivity and its Cost in Quantum Physics. AB - State selective protocols, like entanglement purification, lead to an essentially non-linear quantum evolution, unusual in naturally occurring quantum processes. Sensitivity to initial states in quantum systems, stemming from such non-linear dynamics, is a promising perspective for applications. Here we demonstrate that chaotic behaviour is a rather generic feature in state selective protocols: exponential sensitivity can exist for all initial states in an experimentally realisable optical scheme. Moreover, any complex rational polynomial map, including the example of the Mandelbrot set, can be directly realised. In state selective protocols, one needs an ensemble of initial states, the size of which decreases with each iteration. We prove that exponential sensitivity to initial states in any quantum system has to be related to downsizing the initial ensemble also exponentially. Our results show that magnifying initial differences of quantum states (a Schrodinger microscope) is possible; however, there is a strict bound on the number of copies needed. PMID- 26861078 TI - [The right to banking oversight]. PMID- 26861079 TI - [End of life and vulnerabilities]. PMID- 26861075 TI - Multiple functions of Na/K-ATPase in dopamine-induced salivation of the Blacklegged tick, Ixodes scapularis. AB - Control of salivary secretion in ticks involves autocrine dopamine activating two dopamine receptors: D1 and Invertebrate-specific D1-like dopamine receptors. In this study, we investigated Na/K-ATPase as an important component of the secretory process. Immunoreactivity for Na/K-ATPase revealed basal infolding of lamellate cells in type-I, abluminal interstitial (epithelial) cells in type-II, and labyrinth-like infolding structures opening towards the lumen in type-III acini. Ouabain (10 MUmol l(-1)), a specific inhibitor of Na/K-ATPase, abolished dopamine-induced salivary secretion by suppressing fluid transport in type III acini. At 1 MUmol l(-1), ouabain, the secreted saliva was hyperosmotic. This suggests that ouabain also inhibits an ion resorptive function of Na/K-ATPase in the type I acini. Dopamine/ouabain were not involved in activation of protein secretion, while dopamine-induced saliva contained constitutively basal level of protein. We hypothesize that the dopamine-dependent primary saliva formation, mediated by Na/K-ATPase in type III and type II acini, is followed by a dopamine independent resorptive function of Na/K-ATPase in type I acini located in the proximal end of the salivary duct. PMID- 26861080 TI - [End of life and vulnerability, a public health issue]. AB - End of life and precarity, two words which were linked by the French national observatory for end of life care in its work carried out in 2014. The study provided an overview of current support practices in different areas, highlighting certain lessons to be learned and making recommendations to the different partners involved. PMID- 26861077 TI - Nafamostat mesilate protects against acute cerebral ischemia via blood-brain barrier protection. AB - Serine proteases, such as thrombin, are contributors to the disruption of the blood-brain barrier (BBB) and exacerbate brain damage during ischemic stroke, for which the current clinical therapy remains unsatisfactory. However, the effect of nafamostat mesilate (NM), a synthetic serine protease inhibitor, on BBB disruption following cerebral ischemia is unknown. Here, we investigated the in vivo effect of NM on BBB integrity in rats subjected to transient middle cerebral artery occlusion (MCAO) and explored the possible mechanism in an in vitro BBB model comprising rat brain microvascular endothelial cells and astrocytes after oxygen and glucose deprivation (OGD) in the presence of thrombin. The results showed that NM treatment remarkably attenuated transient MCAO-induced brain infarcts, brain oedema and motor dysfunction in addition to BBB disruption, which might be related to changes in tight junction protein expression and localization. Meanwhile, NM preserved BBB integrity and alleviated the changes in tight junction protein expression and localization and cytoskeleton rearrangement in rat brain microvascular endothelial cells via thrombin inhibition. Our findings suggest that NM treatment can preserve BBB integrity through the inhibition of thrombin, which might be correlated with the regulation of PKCalpha/RhoA/MLC2 pathway components. PMID- 26861081 TI - [Hospital perspectives on the end of life, the case of homeless people]. AB - The hospital is the last refuge for sick homeless people when their illness makes life on the street impossible. The teams often consider these patients as different, difficult and not easy to place in a specific type of care. In palliative care, fewer questions are raised as the patients are hospitalised for their terminal phase. The difficulties often lie in diagnosing the disease and recognising its seriousness and the patient's social situation. PMID- 26861082 TI - [Precarity, vulnerability, anticipating end-of-life care at home]. AB - Many patients want to end their life at home. Care teams adapt to these wishes and organise a form of treatment which blends safety of care and the respect of the expectations of the patients and family members. When factors of precarity increase the vulnerability inherent to the end of life, caregivers anticipate and support as best as they can the difficulties encountered as testified by a hospital at home team in Dax. PMID- 26861083 TI - [Supporting the end of life in a therapeutic coordination apartment]. AB - Therapeutic coordination apartments are medical-social structures which provide accommodation to desocilialized people. For the last 25 years, the association Cordia has been supporting people with debilitating chronic diseases in situations of precarity. The multi-disciplinary approach also ensures that terminally-ill residents are taken care of right up until their last moments. PMID- 26861084 TI - [The nursing role and ethical dimension of end of life care]. AB - Supporting people in situations of precarity at the end of life is often fraught with complex problems, where one form of vulnerability amplifies another. This complexity requires interdisciplinary support, around the nursing care, to reflect together on the meaning of the action taken in an ethical approach. PMID- 26861085 TI - [The Les Morts de la Rue collective, strong social commitment]. AB - The problems faced by homeless people are varied and complex. They require numerous qualities on the part of professionals. Living on the streets often means dying on the streets. Professionals are thereby confronted with practical and ethical questions. They have a key role both in listening and providing support. This article shows the example of the Les Morts de la Rue collective. PMID- 26861086 TI - [Ebola crisis in Guinea: psychosocial support for patients and caregivers]. AB - The experience of the French military health service in the fight against the Ebola epidemic in Guinea, highlights the importance of what favours the emergence of an institutional life in a context of care faced with numerous constraints and extraordinary challenges. The meticulous drawing up of procedures and the juxtaposition of expertise goes hand in hand with the construction of a triangular care system (caregivers-patients-families). This relational approach ensures each player in this system is able to find their place and a balance between constraints and satisfactions, losses and successes, isolation and support. This balance seems to favour individual and group resilience. PMID- 26861087 TI - [A therapeutic garden, a tool to share with patients]. AB - The garden is a place of peace and nature. It draws on all our senses and makes us move our body. It is also an innovative therapeutic tool which can boost the wellbeing of frail or disabled elderly people, as the experience of a nursing home described in this article demonstrates. PMID- 26861088 TI - [Shiatsu therapy for patients and caregivers]. AB - Shiatsu therapy is a manual discipline originating from traditional Chinese medicine. It is developing as an interesting form of support in the fight against stress and chronic fatigue. Shiatsu is used in some hospitals to support not only patients but also caregivers, to prevent burnout. PMID- 26861089 TI - [Physicochemical incompatibilities of injectable drugs]. AB - The physicochemical interactions of injectable drugs administered through a Y site injection port are little known phenomena, poorly documented but very frequent. Physicochemical incompatibility is defined as a chemical reaction between two injectable drugs which come into contact with each other. This chemical reaction may be visible on a macroscopic level or completely invisible. The risks of these interactions are not harmless, ranging from inefficacy to the toxicity of the newly-formed compounds. PMID- 26861090 TI - [Nursing care of amputation stumps]. PMID- 26861091 TI - Prevention of Pressure Ulcers. AB - The nursing procedures at Kensington Hospital place special emphasis on the prevention of pressure ulcers. Pierre has the opportunity to apply the most recent prevention methods with patients suffering from degenerative joint diseases. PMID- 26861092 TI - [Gynecologic brachytherapy: interdisciplinary cooperation]. PMID- 26861093 TI - [Nursing care of acute coronary syndrome]. PMID- 26861094 TI - [Care and removal of Redon drains]. PMID- 26861095 TI - [Picture in clinical hematology]. PMID- 26861096 TI - [Pathogenesis and novel therapy for EBV-related B-cell lymphoma]. AB - Epstein-Barr virus (EBV), a type of gamma-herpes virus, is known to be a tumor virus. About 90% of adults were found to be persistently infected with EBV and this infection is responsible for Burkitt lymphoma (BL), extranodal NK/T cell lymphoma, Hodgkin lymphoma (HL), acquired Immune deficiency syndrome (AIDS) associated lymphoma, and a portion of diffuse large B cell lymphomas (DLBCL). EBV positive DLBCL in the elderly, a disease recognized in Japan, is described in the WHO classification as a new category of DLBCLs. Clinical studies of DLBCLs have since accumulated. We herein describe our clinicopathological study of EBV positive DLBCL in the elderly in the rituximab era, and review EBV-positive B cell lymphoma cases. A potentially promising novel therapy for EBV-positive B cell lymphoma, anti-PD-1 antibody, is then introduced. Finally, we briefly discuss our unpublished study of EBV-positive B cell lymphoma and its microenvironment. PMID- 26861097 TI - [Immunodeficiency-associated Burkitt lymphoma developed in a patient receiving a long-term methotrexate therapy for rheumatoid arthritis]. AB - An increased risk of lymphoproliferative disorders (LPD) has been demonstrated in patients treated with methotrexate (MTX) for rheumatoid arthritis (RA). The role of Epstein-Barr virus (EBV) has been discussed in the pathogenesis of immunodeficiency-associated LPDs. We herein present a RA patient, who developed Burkitt lymphoma during MTX treatment. The patient was a 61-year-old Japanese female with a 10-year history of weekly MTX therapy for RA. She presented with a one-month history of submandibular lymph node swelling and fever. Remarkable increases in serum lactate dehydrogenase and blood EBV DNA were observed. Serology for HIV was negative. Biopsy specimens demonstrated diffuse proliferation of medium-sized lymphoid cells. The cells were positive for CD10, CD20 and BCL6, and negative for BCL2, MUM1, terminal deoxynucleotidyl transferase and CD34. The MIB-1 index was almost 100%. EBV in the tumor cells was identified by using EBV-encoded RNA in situ hybridization. A chromosomal translocation t(8;14) was found and further confirmed by fluorescence in situ hybridization. Her condition improved following discontinuation of MTX and initiation of prednisolone. After three cycles of a dose-reduced CHOP-like regimen, chemotherapy was discontinued due to severe complications. However, there has been no sign of recurrence for six years to date without additional intensive chemotherapy. PMID- 26861098 TI - [Maternal Crohn's disease-related vitamin B12 deficient megaloblastic anemia in an infant]. AB - We report an 11-month-old breast-fed boy with feeding difficulties, lethargy, and developmental delay. Blood examination showed pancytopenia and decreased serum levels of vitamin B12. Anisocytosis and poikilocytes were detected in his peripheral blood, and increased megaloblastosis without leukemic cells was detected in his bone marrow. After the diagnosis of megaloblastic anemia due to vitamin B12 deficiency, symptoms were improved by vitamin B12 administration. Further investigation of the mother identified Crohn's disease and suggested that the supply of vitamin B12 from the mother to the infant, via the placenta during pregnancy and via breast milk after birth, was decreased due to impaired absorption of vitamin B12 in the mother's small intestine. Magnetic resonance imaging of the boy's brain on admission showed cerebral cortex atrophy which had improved by the age of 1 year and 10 months after vitamin B12 treatment, though developmental delay was still evident at the age of 3 years. Infantile vitamin B12 deficiency often presents with nonspecific manifestations, such as developmental delay and failure to thrive, in addition to anemia and is thus not easily diagnosed. To prevent severe neurological sequelae, this condition must be rapidly diagnosed, because a prolonged duration increases the risk of permanent disabilities. PMID- 26861099 TI - [Primary peripheral T-cell lymphoma of the vagina incidentally found at cervical cancer screening]. AB - A 50-year-old woman was referred to our hospital because a mass lesion had been palpable through the vaginal wall during a cervical cancer screening examination. A contrast-enhanced computed tomography (CT) scan and magnetic resonance imaging (MRI) revealed marked thickening of the vaginal wall, constituting a mass 96 mm in diameter. Abnormal FDG uptake was observed in the vaginal mass, but no other lesions were detected by positron emission tomography (PET/CT). A transvaginal biopsy from the tumor revealed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Although endoscopic examinations revealed no signs of infiltration in either the bladder or the rectum, the MRI findings suggested invasion into the adjacent rectal wall. She achieved complete remission after six courses of biweekly THP-COP therapy, to which field radiation (39.6 Gy) was added. PTCL of the vagina is rare and this case therefore merits description in the literature. PMID- 26861100 TI - [Successful treatment with total cranial irradiation for central nervous system involvement of Langerhans cell sarcoma during chemotherapy]. AB - Langerhans cell sarcoma (LCS) is an extremely rare neoplasm of Langerhans cell origin characterized by systemic involvement and a poor prognosis. There are, however, few reports of LCS with central nervous system involvement. We experienced a patient with LCS recurrence in the brain that appeared during systemic chemotherapy. The brains lesions eventually responded to total cranial irradiation. A 60-year-old female presented with systemic lymphadenopathy. LCS was diagnosed based on neck lymph node biopsy findings. Two cycles of ESHAP induced marked regression of her lymphadenopathy, but FDG-PET/CT scan revealed new lesions in the central nervous system and her disorientation gradually worsened. We administered 37.5 Gy of total cranial irradiation which improved her consciousness and shrank the brain tumors as demonstrated by MRI. The patient's clinical course indicates that radiation therapy may be effective for central nervous system involvement of LCS even if the lesion is resistant to systemic chemotherapy. PMID- 26861101 TI - [Dysfibrinogenemia developed in a pregnant woman who has fibrinogen AalphaThr312Ala (ACT/GCT) polymorphism]. AB - Blood coagulation factors play an essential role in pregnancy. We describe a 30 year-old pregnant woman whose course was complicated by dysfibrinogenemia with polymorphism of fibrinogen AalphaThr312Ala (rs6050) GG genotype. She was admitted to our hospital for genital bleeding and a huge subchorionic hematoma at 6 gestational weeks. Her first pregnancy and delivery had been uneventful, whereas her second and third pregnancies had resulted in spontaneous abortions with massive subchorionic hematomas. Her fibrinogen activity level was 125 mg/dl and this was lower than her fibrinogen antigen level. We administered tranexamic acid early in the pregnancy, and the subchorionic hematoma diminished in size in accordance with the increase of her fibrinogen level. At 16 gestational weeks, her D-dimer levels were elevated, and heparin treatment was initiated as an alternative. A male infant was delivered at 36 gestational weeks. Intrapartum hemorrhage was 600 g. Patients with coagulation abnormalities are often asymptomatic in the absence of pregnancy. However, when they become pregnant, the spontaneous abortion rate is high. Careful observation and effective management of coagulation abnormalities are essential for such patients to carry their pregnancies to term. PMID- 26861102 TI - [Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma]. AB - We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD. PMID- 26861103 TI - [Multiple organ failure presumably due to alkylating agents used as preconditioning drugs for autologous peripheral blood stem cell transplantation in an acute promyelocytic leukemia]. AB - A 52-year-old male was diagnosed as having acute promyelocytic leukemia (APL) in 2006. He received induction chemotherapy including all-trans retinoic acid and initially achieved a complete remission (CR). After several courses of consolidation therapy combining anthracyclines and cytarabine, he maintained CR. In 2009, an APL relapse was diagnosed, and he was treated with arsenic trioxide. Since he achieved a second CR, he underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) with a conditioning regimen consisting of busulfan and melphalan. At four months after auto-PBSCT, he developed a pneumothorax and acute respiratory failure. He died despite intensive therapy. Autopsy findings included various atypical and apoptotic cells in his pulmonary tissue. These changes were confirmed in multiple organs throughout the body, suggesting them to be drug-induced. The findings in this case suggested multiple organ failure due to alkylating agents. PMID- 26861104 TI - [Refractory primary myeloid sarcoma of the breast with MLL-AF9 rearrangement]. AB - A 28-year-old woman presented with a right breast mass and axillary lymphadenopathy. Biopsy of the breast mass revealed myeloid sarcoma (MS) staining positive for CD4, CD13, CD33, and CD68/KP-1. Bone marrow aspiration revealed leukemic cell infiltration (9%). Leukemic cells possessed cytogenetic abnormalities of +8 and t(9;11)(p22;q23) with +22 (lymph node only), and molecular analyses confirmed the MLL-AF9 fusion gene. After induction chemotherapy and 2(nd) consolidation therapy, complete remission was maintained. However, during consolidation radiotherapy for the breast mass, the disease progressed in both the breast and bone marrow. She received re-induction therapy and proceeded to allogeneic stem cell transplantation. However, the disease relapsed in the breast soon after transplantation, and she died from disease progression. Trisomy 8 and the MLL-AF9 fusion gene have been reported in cases with MS in the breast. Trisomy 22 found additionally and exclusively in the extramedullary lesion implies extramedullary progression of MS from the medullary site of origin and may have been associated with the distinctive therapy resistance of these lesions in our case. PMID- 26861105 TI - [Neurolymphomatosis of the sciatic nerve diagnosed by FDG-PET/CT]. AB - Neurolymphomatosis is a rare manifestation of malignant lymphoma. The involvement of peripheral nerves has mostly been described as dissemination of a systemic lymphoma. In contrast, primary peripheral nerve lymphoma is extremely rare. A 68 year-old man presented in January 2014 with a sensory disturbance in the left lower extremity. There were no obvious findings on MRI or CT that could account for his symptoms. After 1 year of symptomatic treatment, the patient was managed conservatively for an additional year. However, his symptoms worsened. FDG-PET/CT showed high FDG uptake in the left sciatic nerve. Biopsy of the lesion revealed diffuse large B cell lymphoma. PMID- 26861108 TI - [Erratum]. PMID- 26861106 TI - [Systemic organ invasion accompanied by immunophenotypic change observed in extraosseous plasmacytoma]. AB - We report a 57-year-old man who was diagnosed based on morphological findings as having extraosseous plasmacytoma of the left lower eyelid. Tumor cells were positive not only for CD38 and CD138, but also for CD19 and surface immunoglobulin lambda chain. He obtained a complete remission with irradiation and VAD therapy, but the disease relapsed one year later in the testis and popliteal fossa. Because tumor cells appeared to be blastoid, CHOP therapy was administered, and the patient achieved a temporary remission. Cytoplasmic lambda chain-positive and CD19-negative tumors eventually recurred at multiple sites including the central nervous system but not in the bone marrow. Treatment with the BD regimen and lenalidomide failed, and he died four years after the initial diagnosis. PMID- 26861109 TI - The influence of different anticoagulants and time-delayed sample processing and measurements on human monocyte subset and monocyte-platelet aggregate analyses. AB - BACKGROUND: Measuring human monocyte subsets (CD14++CD16-, CD14++CD16+, and CD14 + CD16++) and subset-specific monocyte-platelet aggregates (MPA) is vulnerable to analytical bias due to unavailability of a standardized methodology. We aimed to address this issue by focusing on the impacts of time-delayed sample processing and measurement between two commonly used anticoagulants. METHODS: Ethylenediaminetetraacetic acid (EDTA)- and sodium citrate (SC)-anticoagulated blood samples from 12 healthy donors were subject to either delayed (2-h delay, kept at 4 degrees C) or immediate processing (without fixation) before four-color flow cytometry (FCM) analysis. RESULTS: In SC-anticoagulated samples, a 2-h delay in sample processing contributed to a significant decrease in CD14++CD16- monocyte percent and a reciprocal increase in CD14++CD16+ monocytes, as well as increases in all three subset-specific MPA. Similar slight, but non-significant changes were observed in EDTA-treated samples. In samples processed immediately and stored at 4 degrees C, delayed measurement at 0, 1, 3, and 5 h after processing led to a time-dependent decrease in CD14++CD16- monocyte percent and a reciprocal increase in CD14++CD16+ subset in SC-treated, but not in EDTA-treated, samples. Moreover, a time-dependent increase in all three subset-specific MPA was observed in SC-treated samples, which, to a lesser extent, was only observed in CD14++CD16+ MPA in EDTA-treated samples after storage at 4 degrees C for 3-5 h after processing. CONCLUSIONS: We recommend EDTA for anticoagulation. Additionally, sample should be stored at 4 degrees C and processing and measuring should be performed within 2 h after harvest and 3 h after processing, respectively. (c) 2016 International Clinical Cytometry Society. PMID- 26861110 TI - Field-programmable beam reconfiguring based on digitally-controlled coding metasurface. AB - Digital phase shifters have been applied in traditional phased array antennas to realize beam steering. However, the phase shifter deals with the phase of the induced current; hence, it has to be in the path of each element of the antenna array, making the phased array antennas very expensive. Metamaterials and/or metasurfaces enable the direct modulation of electromagnetic waves by designing subwavelength structures, which opens a new way to control the beam scanning. Here, we present a direct digital mechanism to control the scattered electromagnetic waves using coding metasurface, in which each unit cell loads a pin diode to produce binary coding states of "1" and "0". Through data lines, the instant communications are established between the coding metasurface and the internal memory of field-programmable gate arrays (FPGA). Thus, we realize the digital modulation of electromagnetic waves, from which we present the field programmable reflective antenna with good measurement performance. The proposed mechanism and functional device have great application potential in new-concept radar and communication systems. PMID- 26861111 TI - Effects of Heterogeneous Diffuse Fibrosis on Arrhythmia Dynamics and Mechanism. AB - Myocardial fibrosis is an important risk factor for cardiac arrhythmias. Previous experimental and numerical studies have shown that the texture and spatial distribution of fibrosis may play an important role in arrhythmia onset. Here, we investigate how spatial heterogeneity of fibrosis affects arrhythmia onset using numerical methods. We generate various tissue textures that differ by the mean amount of fibrosis, the degree of heterogeneity and the characteristic size of heterogeneity. We study the onset of arrhythmias using a burst pacing protocol. We confirm that spatial heterogeneity of fibrosis increases the probability of arrhythmia induction. This effect is more pronounced with the increase of both the spatial size and the degree of heterogeneity. The induced arrhythmias have a regular structure with the period being mostly determined by the maximal local fibrosis level. We perform ablations of the induced fibrillatory patterns to classify their type. We show that in fibrotic tissue fibrillation is usually of the mother rotor type but becomes of the multiple wavelet type with increase in tissue size. Overall, we conclude that the most important factor determining the formation and dynamics of arrhythmia in heterogeneous fibrotic tissue is the value of maximal local fibrosis. PMID- 26861113 TI - Percutaneous Transluminal Angioplasty and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) Trial. AB - BACKGROUND: Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. In interventional cardiology, drug-eluting stents (DES) have shown better patency rates and are standard practice nowadays. An investigator-initiated, multicenter, randomized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions. METHODS AND RESULTS: Adults with critical limb ischemia (Rutherford category >=4) and infrapopliteal lesions were randomized to receive PTA+/-BMS or DES with paclitaxel. Primary end point was 6-month primary binary patency of treated lesions, defined as <=50% stenosis on computed tomographic angiography. Stenosis >50%, retreatment, major amputation, and critical limb ischemia-related death were regarded as treatment failure. Severity of failure was assessed with an ordinal score, ranging from vessel stenosis through occlusion to the clinical failures. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) received PTA+/-BMS. Six-month patency rates were 48.0% for DES and 35.1% for PTA+/-BMS (P=0.096) in the modified-intention-to treat and 51.9% and 35.1% (P=0.037) in the per-protocol analysis. The ordinal score showed significantly worse treatment failure for PTA+/-BMS versus DES (P=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment, with a trend toward significance (P=0.066). Less minor amputations occurred after DES until 6 months post-treatment (P=0.03). CONCLUSIONS: In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA+/-BMS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289. PMID- 26861112 TI - NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions. AB - NLRC5 is a transcriptional regulator of MHC class I (MHCI), which maintains high MHCI expression particularly in T cells. Recent evidence highlights an important NK-T-cell crosstalk, raising the question on whether NLRC5 specifically modulates this interaction. Here we show that NK cells from Nlrc5-deficient mice exhibit moderate alterations in inhibitory receptor expression and responsiveness. Interestingly, NLRC5 expression in T cells is required to protect them from NK cell-mediated elimination upon inflammation. Using T-cell-specific Nlrc5 deficient mice, we show that NK cells surprisingly break tolerance even towards 'self' Nlrc5-deficient T cells under inflammatory conditions. Furthermore, during chronic LCMV infection, the total CD8(+) T-cell population is severely decreased in these mice, a phenotype reverted by NK-cell depletion. These findings strongly suggest that endogenous T cells with low MHCI expression become NK-cell targets, having thus important implications for T-cell responses in naturally or therapeutically induced inflammatory conditions. PMID- 26861114 TI - Comparative transcriptome analysis of peripheral blood mononuclear cells in hepatitis B-related acute-on-chronic liver failure. AB - Analysis of the transcriptome of peripheral blood mononuclear cells (PBMCs) from patients with hepatitis B-related acute-on-chronic liver failure (HBV-ACLF) is essential to elucidate the pathogenesis of HBV-ACLF and identify HBV-ACLF specific biomarkers. In this study, high-throughput sequencing was performed to characterize the transcriptome of PMBCs from patients with HBV-ACLF. Specifically, 2381 differentially expressed genes (DEGs) and 776 differentially expressed transcripts were identified through comparisons with patients with chronic hepatitis B (CHB) and healthy controls. Gene Ontology (GO) analysis identified 114 GO terms that were clustered into 12 groups. We merged 10 dysregulated genes selected from these grouped GO terms and non-clustered terms with four significant genes with a specificity of >0.8 in the HBV-ACLF patients to obtain a set of 13 unique genes. The quantitative real-time polymerase chain reaction (qRT-PCR) validation of the top six genes (CYP19A1, SEMA6B, INHBA, DEFT1P, AZU1 and DEFA4) was consistent with the results of messenger ribonucleic acid (mRNA) sequencing. A further receiver operating characteristic (ROC) analysis revealed that the areas under the ROC curves of the six genes were all >0.8, which indicated their significant diagnostic potentials for HBV-ACLF. CONCLUSION: The transcriptome characteristics of PBMCs are altered in patients with HBV-ACLF, and six genes may serve as biomarkers of HBV-ACLF. PMID- 26861116 TI - Methylene blue attenuates mitochondrial dysfunction of rat kidney during experimental acute pancreatitis. AB - OBJECTIVE: The disturbance of mitochondrial functions has been considered as one of the mechanisms of pathogenesis of acute pancreatitis (AP) followed by kidney failure. This study was aimed to investigate the effects of methylene blue (MB) on pancreas and kidney mitochondrial respiratory functions during experimental acute pancreatitis in rats. METHODS: AP was induced by administrating sodium taurocholate into the pancreatic duct of male Wistar rats. The rats were divided into three groups: the MB group, MB (5 mg/kg) was injected intravenously 10 min prior to AP induction; the AP group, saline solution was injected intravenously 10 min prior to AP induction; and the sham operation group, isotonic sodium chlorine was used instead of sodium taurocholate. The animals were sacrificed after 24 h. The pancreas and kidney were removed for mitochondrial assay by oxygraphic and spectrophotometric methods. RESULTS: Intravenous injection of MB did not prevent AP-induced inhibition of pancreatic mitochondrial respiration; however, MB significantly improved kidney mitochondrial respiratory functions with complex I-dependent substrates glutamate and malate. The activity of complex I of mitochondria isolated from AP-damaged kidney was increased after pretreatment with MB. However, MB did not affect AP-inhibited kidney mitochondrial respiration with succinate. MB had no protective effects on amylase activity or on urea content in serum in AP. CONCLUSION: The disturbances of kidney mitochondrial energy metabolism in experimental model of severe AP can be ameliorated by MB administration. PMID- 26861118 TI - Quantum cognition based on an ambiguous representation derived from a rough set approximation. AB - Over the last years, in a series papers by Arecchi and others, a model for the cognitive processes involved in decision making has been proposed and investigated. The key element of this model is the expression of apprehension and judgment, basic cognitive process of decision making, as an inverse Bayes inference classifying the information content of neuron spike trains. It has been shown that for successive plural stimuli this inference, equipped with basic non algorithmic jumps, is affected by quantum-like characteristics. We show here that such a decision making process is related consistently with an ambiguous representation by an observer within a universe of discourse. In our work the ambiguous representation of an object or a stimuli is defined as a pair of maps from objects of a set to their representations, where these two maps are interrelated in a particular structure. The a priori and a posteriori hypotheses in Bayes inference are replaced by the upper and lower approximations, correspondingly, for the initial data sets that are derived with respect to each map. Upper and lower approximations herein are defined in the context of "rough set" analysis. The inverse Bayes inference is implemented by the lower approximations with respect to the one map and for the upper approximation with respect to the other map for a given data set. We show further that, due to the particular structural relation between the two maps, the logical structure of such combined approximations can only be expressed as an orthomodular lattice and therefore can be represented by a quantum rather than a Boolean logic. To our knowledge, this is the first investigation aiming to reveal the concrete logic structure of inverse Bayes inference in cognitive processes. PMID- 26861120 TI - Setting priorities in health research using the model proposed by the World Health Organization: development of a quantitative methodology using tuberculosis in South Africa as a worked example. AB - BACKGROUND: Setting priorities is important in health research given the limited resources available for research. Various guidelines exist to assist in the priority setting process; however, priority setting still faces significant challenges such as the clear ranking of identified priorities. The World Health Organization (WHO) proposed a Disability Adjusted Life Year (DALY)-based model to rank priorities by research area (basic, health systems and biomedical) by dividing the DALYs into 'unavertable with existing interventions', 'avertable with improved efficiency' and 'avertable with existing but non-cost-effective interventions', respectively. However, the model has conceptual flaws and no clear methodology for its construction. Therefore, the aim of this paper was to amend the model to address these flaws, and develop a clear methodology by using tuberculosis in South Africa as a worked example. METHODS: An amended model was constructed to represent total DALYs as the product of DALYs per person and absolute burden of disease. These figures were calculated for all countries from WHO datasets. The lowest figures achieved by any country were assumed to represent 'unavertable with existing interventions' if extrapolated to South Africa. The ratio of 'cost per patient treated' (adjusted for purchasing power and outcome weighted) between South Africa and the best country was used to calculate the 'avertable with improved efficiency section'. Finally, 'avertable with existing but non-cost-effective interventions' was calculated using Disease Control Priorities Project efficacy data, and the ratio between the best intervention and South Africa's current intervention, irrespective of cost. RESULTS: The amended model shows that South Africa has a tuberculosis burden of 1,009,837.3 DALYs; 0.009% of DALYs are unavertable with existing interventions and 96.3% of DALYs could be averted with improvements in efficiency. Of the remaining DALYs, a further 56.9% could be averted with existing but non-cost effective interventions. CONCLUSIONS: The amended model was successfully constructed using limited data sources. The generalizability of the data used is the main limitation of the model. More complex formulas are required to deal with such potential confounding variables; however, the results act as starting point for development of a more robust model. PMID- 26861117 TI - Assessment of Fidelity in Interventions to Improve Hand Hygiene of Healthcare Workers: A Systematic Review. AB - OBJECTIVE: Compliance with hand hygiene in healthcare workers is fundamental to infection prevention yet remains a challenge to sustain. We examined fidelity reporting in interventions to improve hand hygiene compliance, and we assessed 5 measures of intervention fidelity: (1) adherence, (2) exposure or dose, (3) quality of intervention delivery, (4) participant responsiveness, and (5) program differentiation. DESIGN: Systematic review METHODS: A librarian performed searches of the literature in PubMed, Cumulative Index to Nursing and Allied Health (CINAHL), Cochrane Library, and Web of Science of material published prior to June 19, 2015. The review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews, and assessment of study quality was conducted for each study reviewed. RESULTS: A total of 100 studies met the inclusion criteria. Only 8 of these 100 studies reported all 5 measures of intervention fidelity. In addition, 39 of 100 (39%) failed to include at least 3 fidelity measures; 20 of 100 (20%) failed to include 4 measures; 17 of 100 (17%) failed to include 2 measures, while 16 of 100 (16%) of the studies failed to include at least 1 measure of fidelity. Participant responsiveness and adherence to the intervention were the most frequently unreported fidelity measures, while quality of the delivery was the most frequently reported measure. CONCLUSIONS: Almost all hand hygiene intervention studies failed to report at least 1 fidelity measurement. To facilitate replication and effective implementation, reporting fidelity should be standard practice when describing results of complex behavioral interventions such as hand hygiene. PMID- 26861121 TI - Acceptance of Reduced-Risk Drinking as a Therapeutic Goal within the Polish Alcohol Treatment System. AB - AIMS: To assess views on the feasibility and acceptability of reduced-risk drinking (RRD) strategies within the very homogenous and abstinence-oriented Polish alcohol treatment system. METHODS: By online survey in 2014/15 we enquired into current attitudes of nationwide sample of professionals working in outpatient alcohol treatment facilities regarding non-abstinence goals as a function of severity of the disorder (abuse/dependence) and the finality of the outcome goal. RESULTS: Questionnaires were completed by experienced addiction therapists, trained primarily in cognitive-behavioral therapy (n= 246, response rate = 50%). Only one third accept RRD for alcohol dependent clients (fully or partially), the three fourths accept RRD for alcohol abusing clients (fully or partially). RRD as an intermediate goal of treatment is more accepted than when set up as a final treatment objective. RRD had significantly higher level of acceptance among younger professionals. Compared to male respondents, females were more open to offering RRD to patients experiencing alcohol-related problems. Finally, therapists working according to the principles of motivational interviewing or solution focused brief therapy were significantly more in favor of RRD than others. CONCLUSION: Comparing with other countries, the acceptance of RRD as a therapeutic objective in Poland is moderately low. Mistrust toward RRD strategies is mainly fueled by a belief that this strategy is not effective plus its inconsistency with therapists' own therapeutic philosophy. PMID- 26861124 TI - Replacing the term chronic kidney disease. PMID- 26861123 TI - Screen-based behaviour in school-aged children with long-term illness. AB - BACKGROUND: Evidence is lacking on the screen-based behaviour of adolescents with a chronic condition. The aim of our study was to analyse differences in screen based behaviour of adolescents by long-term illness, asthma and learning disabilities. METHODS: We used data from the cross-sectional Health Behaviour of School-aged Children study collected in 2014 among Slovak adolescents (age 13 to 15 years old, N = 2682, 49.7 % boys). We analysed the associations between screen based behaviour and long-term illness, asthma and learning disabilities using logistic regression models adjusted for gender. RESULTS: We found no associations between screen-based behaviour and long-term illness, except that children with asthma had a 1.60-times higher odds of excessively playing computer games than healthy children (95 % confidence interval of odds ratio (CI): 1.11-2.30). Children with learning disabilities had 1.71-times higher odds of risky use of the Internet (95 % CI: 1.19-2.45). CONCLUSION: Adolescents with a long-term illness or with a chronic condition or a learning disability do not differ from their peers in screen-based activities. Exceptions are children with asthma and children with learning disabilities, who reported more risky screen-based behaviour. PMID- 26861122 TI - Quantitative analysis of insulin-like growth factor 2 receptor and insulin-like growth factor binding proteins to identify control mechanisms for insulin-like growth factor 1 receptor phosphorylation. AB - BACKGROUND: The insulin-like growth factor (IGF) system impacts cellular development by regulating proliferation, differentiation, and apoptosis, and is an attractive therapeutic target in cancer. The IGF system is complex, with two ligands (IGF1, IGF2), two receptors (IGF1R, IGF2R), and at least six high affinity IGF-binding proteins (IGFBPs) that regulate IGF ligand bioavailability. While the individual components of the IGF system are well studied, the question of how these different components integrate as a system to regulate cell behavior is less clear. RESULTS: To analyze the relative importance of different mechanisms that control IGF network activity, we developed a mass-action kinetic model incorporating cell surface binding, phosphorylation, and intracellular trafficking events. The model was calibrated and validated using experimental data collected from OVCAR5, an immortalized ovarian cancer cell line. We then performed model analysis to examine the ability of IGF2R or IGFBPs to counteract phosphorylation of IGF1R, a critical step for IGF network activation. This analysis suggested that IGF2R levels would need to be 320-fold greater than IGF1R in order to decrease pIGF1R by 25 %, while IGFBP levels would need to be 390-fold greater. Analysis of The Cancer Genome Atlas (TCGA) data set suggested that this level of overexpression is unlikely for IGF2R in ovarian, breast, and colon cancer. In contrast, IGFBPs can likely reach these levels, suggesting that IGFBPs are the more critical regulator of IGF1R network activity. Levels of phosphorylated IGF1R were insensitive to changes in parameters regulating the IGF2R arm of the network. CONCLUSIONS: Using a mass-action kinetic model, we determined that IGF2R plays a minor role in regulating the activity of IGF1R under a variety of conditions and that due to their high expression levels, IGFBPs are the dominant mechanism to regulating IGF network activation. PMID- 26861126 TI - Vasculogenic and Angiogenic Pathways in Moyamoya Disease. AB - BACKGROUND: Moyamoya disease (MMD) is a slowly progressing steno-occlusive cerebrovascular disease. The typical moyamoya vessels, which originate from an initial stenosis of the internal carotid, highlight that increased and/or abnormal angiogenic, vasculogenic and arteriogenic processes are involved in the disease pathophysiology. OBJECTIVE: Herein, we summarize the current knowledge on the most important signaling pathways involved in MMD vessel formation, particularly focusing on the expression of growth factors and function of endothelial progenitor cells (EPCs). METHODS AND RESULTS: Higher plasma concentrations of vascular endothelial growth factor, matrix metalloproteinase, hepatocyte growth factor, and interleukin-1beta were reported in MMD. A specific higher level of basic fibroblast growth factor was also found in the cerebrospinal fluid of these patients. Finally, the number and the functionality of EPCs were found to be increased. In spite of the available data, the approaches and findings reported so far do not give an evident correlation between the expression levels of the aforementioned growth factors and MMD severity. Furthermore, the controversial results provided by studies on EPCs, do not permit to understand the true involvement of these cells in MMD pathophysiology. CONCLUSION: Further studies should thus be implemented to extend our knowledge on processes regulating both the arterial stenosis and the excessive formation of collateral vessels. Moreover, we suggest advances of integrated approaches and functional assays to correlate biological and clinical data, arguing for the development of new therapeutic applications for MMD. PMID- 26861115 TI - Immunologic response in treatment-naive HIV-2-infected patients: the IeDEA West Africa cohort. AB - INTRODUCTION: Response to antiretroviral therapy (ART) among individuals infected with HIV-2 is poorly described. We compared the immunological response among patients treated with three nucleoside reverse-transcriptase inhibitors (NRTIs) to boosted protease inhibitor (PI) and unboosted PI-based regimens in West Africa. METHODS: This prospective cohort study enrolled treatment-naive HIV-2 infected patients within the International Epidemiological Databases to Evaluate AIDS collaboration in West Africa. We used mixed models to compare the CD4 count response to treatment over 12 months between regimens. RESULTS: Of 422 HIV-2 infected patients, 285 (67.5%) were treated with a boosted PI-based regimen, 104 (24.6%) with an unboosted PI-based regimen and 33 (7.8%) with three NRTIs. Treatment groups were comparable with regard to gender (54.5% female) and median age at ART initiation (45.3 years; interquartile range 38.3 to 51.8). Treatment groups differed by clinical stage (21.2%, 16.8% and 17.3% at CDC Stage C or World Health Organization Stage IV for the triple NRTI, boosted PI and unboosted PI groups, respectively, p=0.02), median length of follow-up (12.9, 17.7 and 44.0 months for the triple NRTI, the boosted PI and the unboosted PI groups, respectively, p<0.001) and baseline median CD4 count (192, 173 and 129 cells/ul in the triple NRTI, the boosted PI and the unboosted PI-based regimen groups, respectively, p=0.003). CD4 count recovery at 12 months was higher for patients treated with boosted PI-based regimens than those treated with three NRTIs or with unboosted PI-based regimens (191 cells/ul, 95% CI 142 to 241; 110 cells/ul, 95% CI 29 to 192; 133 cells/ul, 95% CI 80 to 186, respectively, p=0.004). CONCLUSIONS: In this observational study using African data, boosted PI containing regimens had better immunological response compared to triple NRTI combinations and unboosted PI-based regimens at 12 months. A randomized clinical trial is still required to determine the best initial regimen for treating HIV-2 infected patients. PMID- 26861125 TI - Creatine synthesis and exchanges between brain cells: What can be learned from human creatine deficiencies and various experimental models? AB - While it has long been thought that most of cerebral creatine is of peripheral origin, the last 20 years has provided evidence that the creatine synthetic pathway (AGAT and GAMT enzymes) is expressed in the brain together with the creatine transporter (SLC6A8). It has also been shown that SLC6A8 is expressed by microcapillary endothelial cells at the blood-brain barrier, but is absent from surrounding astrocytes, raising the concept that the blood-brain barrier has a limited permeability for peripheral creatine. The first creatine deficiency syndrome in humans was also discovered 20 years ago (GAMT deficiency), followed later by AGAT and SLC6A8 deficiencies, all three diseases being characterized by creatine deficiency in the CNS and essentially affecting the brain. By reviewing the numerous and latest experimental studies addressing creatine transport and synthesis in the CNS, as well as the clinical and biochemical characteristics of creatine-deficient patients, our aim was to delineate a clearer view of the roles of the blood-brain and blood-cerebrospinal fluid barriers in the transport of creatine and guanidinoacetate between periphery and CNS, and on the intracerebral synthesis and transport of creatine. This review also addresses the question of guanidinoacetate toxicity for brain cells, as probably found under GAMT deficiency. PMID- 26861128 TI - [Not Available]. PMID- 26861127 TI - [Localized, irregular pigmentation of the maxillary gingiva]. PMID- 26861129 TI - Mesial temporal lobe epilepsy with childhood febrile seizure. AB - OBJECTIVES: To evaluate the demographic and clinical manifestations of patients with mesial temporal sclerosis and temporal lobe epilepsy (MTS-TLE) with childhood febrile seizure (FS) and establishing the potential differences as compared to those without FS. We also investigated the surgery outcome in these two groups of patients. MATERIALS AND METHODS: In this retrospective study, all patients with a clinical diagnosis of drug-resistant TLE due to mesial temporal sclerosis, who underwent epilepsy surgery at Jefferson Comprehensive Epilepsy Center, were recruited. Patients were prospectively registered in a database from 1986 through 2014. Postsurgical outcome was classified into two groups; seizure free or relapsed. Clinical manifestations and outcome were compared between patients with MTS-TLE with FS and those without FS. RESULTS: Two hundred and sixty-two patients were eligible for this study. One hundred and seventy patients (64.9%) did not have FS in their childhood, while 92 patients (35.1%) reported experiencing FS in their childhood. Demographic and clinical characteristics of these two groups of patients were not different. Postoperative seizure outcome was not statistically different between these two groups of patients (P = 0.19). CONCLUSIONS: When MTS is the pathological substrate of TLE, clinical manifestations and response to surgical treatment of patients are very similar in patients with history of febrile seizure in their childhood compared to those without such an experience. In other words, when the subgroup of patients with MTS-TLE and drug-resistant seizures is examined history of childhood febrile seizure loses its value as a distinguishing factor in characteristics or predictive factor for surgery outcome. PMID- 26861130 TI - Wire fixation of internal distractor for cranial vault remodeling. AB - BACKGROUND: Posterior cranial vault distraction osteogenesis is currently used to enlarge the cranial volume and control the intracranial pressure. This procedure carries the risk of hardware dislocation, and especially in infants, as their skull being thin, the screws may damage the underlying dura. TECHNICAL NOTE: In this paper, the authors describe a simple method to fixate the internal distractor to the skull vault in case of thin calvaria using metallic wires. DISCUSSION: This method allows a strong and tight application of the distractor to the osteotomy margins and reduces the risks of loosening of the device and the risk of dural tears. It is particularly useful in young children or in case of diffuse digitate impressions with areas of reduced thickness of the skull bone. PMID- 26861131 TI - Telemetric intracranial pressure monitoring: a noninvasive method to follow up children with complex craniosynostoses. A case report. AB - INTRODUCTION: There are no reliable noninvasive methods of monitoring ICP. Most assessments are made by indirect measures and are difficult to follow over time. Invasive studies can be used but up until now have required in-hospital transcutaneous measurements. Accurate ICP recordings over longer periods of time can be very valuable in timing different surgical procedures in syndromal cases. This case shows that telemetric ICP monitoring can be used for long-term follow up in patients that may need repeated surgeries related to their craniosynostosis condition. CASE REPORT: In this report, the telemetric ICP probe (Raumedic Neurovent-P-tel) was implanted before surgery and was used for repeated "noninvasive" ICP recordings pre- and postoperatively in a patient with craniosynostosis. The patient was an eight-year-old girl with pansynostosis with only the right lambdoid suture open. A telemetric ICP probe was implanted the day before cranial vault remodeling and the ICP was monitored pre- and postoperatively. The ICP was above 15 mmHg 72.2 % of the monitoring time before surgery, and the amplitude of the curve was greater than normal suggesting impaired compliance. Direct postoperative ICP was normal, and the amplitude was lower. The ICP was then monitored both in out-patient clinic and in four longer hospital stays. Both the values and the curves were analyzed, and the time with ICP above 15 mmHg decreased over time, and the waveform amplitude of the curves improved. CONCLUSION: This "noninvasive" way of recording ICP is a feasible and helpful tool in decision-making and intervening in patients with craniosynostosis. PMID- 26861132 TI - Central nervous system and cervical spine abnormalities in Apert syndrome. AB - PURPOSE: Apert syndrome characterized by acrocephalosyndactyly is a rare autosomal dominant congenital malformation with a prevalence of 1/65,000 births. With an extensive range of phenotypic and developmental manifestations, its management requires a multidisciplinary approach. A variety of craniofacial, central nervous system (CNS), and cervical spine abnormalities have been reported in these patients. This study aimed to determine the incidence of these CNS abnormalities in our case series. METHODS: Retrospective review of Australian Craniofacial Unit (ACFU) database for Apert patients was performed. Data collected that included demographics, place of origin, age at presentation, imaging performed, and images were reviewed and recorded. Where available, developmental data was also recorded. RESULTS: Ninety-four patients seen and managed at the ACFU had their CNS and cervical spine abnormalities documented. The main CNS abnormalities were prominent convolutional markings (67 %), ventriculomegaly (48 %), crowded foramen magnum (36 %), deficient septum pellucidum (13 %), and corpus callosum agenesis in 11 %. Major C-spine findings were present in 50.8 % of patients and included fusion of posterior elements of C5/C6 (50 %) and C3/4 (27 %). Multilevel fusion was seen in 20 %. Other abnormalities were C1 spina bifida occulta (7 %) and atlanto-axial subluxation (7 %). CONCLUSION: Multiple CNS and cervical spine (c-spine) abnormalities are common in Apert syndrome. The significance of these abnormalities remains largely unknown. Further research is needed to better understand the impact of these findings on growth, development, and treatment outcomes. PMID- 26861133 TI - Use of adaptive network burst detection methods for multielectrode array data and the generation of artificial spike patterns for method evaluation. AB - OBJECTIVE: Multielectrode arrays are an informative extracellular recording technology that enables the analysis of cultured neuronal networks and network bursts (NBs) are a dominant feature observed in these recordings. This paper focuses on the validation of NB detection methods on different network activity patterns and developing a detection method that performs robustly across a wide variety of activity patterns. APPROACH: A firing rate based approach was used to generate artificial spike timestamps where NBs were introduced as episodes where the probability of spiking increases. Variations in firing and bursting characteristics were also included. In addition, an improved methodology of detecting NBs is proposed, based on time-binned average firing rates and time overlaps of single channel bursts. The robustness of the proposed method was compared against three existing algorithms using simulated, publicly available and newly acquired data. MAIN RESULTS: A range of activity patterns were generated by changing simulation variables that correspond to NB duration (40 2200 ms), intervals (0.3-16 s), firing rates (0.1-1 spikes s(-1)), local burst percentage (0%-90%), number of channels in local bursts (20-40) as well as the number of tonic and frequently-bursting channels. By extracting simulation parameters directly from real data, we generated synthetic data that closely resemble activity of mouse and rat cortical cultures at native and chemically perturbed states. In 50 simulated data sets with randomly selected parameter values, the improved NB detection method performed better (ascertained by the f measure) than three existing methods (p < 0.005). The improved method was also able to detect clustered, long-tailed and short-frequent NBs on real data. SIGNIFICANCE: This work presents an objective method of assessing the applicability of NB detection methods for different neuronal activity patterns. Furthermore, it proposes an improved NB detection method that can be used robustly across a range of data types. PMID- 26861134 TI - Negative Correlation Between miR-326 and Ets-1 in Regulatory T Cells from new Onset SLE Patients. AB - To analyze the relationship between miR-326 and Ets-1 mRNA levels in Treg cells and clinical manifestations in patients with SLE and explore the role of miR-326 and Ets-1 in the pathogenesis and activity of SLE. Twenty-five new-onset SLE patients without treatment, twenty-eight inactive SLE patients (SLEDA <= 4) and twenty-two healthy controls were included in the present study. Clinical data of SLE patients were recorded. Treg cells were purified by MACS from 20 ml peripheral blood, in which the quantity of miR-326 and Ets-1 mRNA were assessed by real-time PCR. Data were analyzed using SPSS Version 17.0. The nonparametric Mann-Whitney U test was used to compare the groups, The Spearman test was used for correlation analyses. Two-tailed p values <0.05 were considered statistically significant. 1.The level of miR-326 was significantly higher in Treg cells from SLE patients [1.98(0.592,6.148)] than that in healthy controls [0.921(0.345, 1.879)] (p = 0.032). The difference between new-onset SLE patients [6.192(0.673, 15.298)] and healthy controls was significant (p = 0.019). Significant difference of the miR-326 expression was found between new-onset SLE patients with serous cavity effusion and new-onset SLE patients without it(P<0.05). Significant positive correlation was found between the expression of miR-326 mRNA in Treg cells with CRP and anti-C1q antibody from new-onset SLE patients. 2. The level of Ets-1 mRNA was decreased in SLE patients [0.382(0.232, 0.572)] compared to healthy controls(p = 0.013). The difference was also found in new-onset SLE patients [0.222(0.125, 0.296)] while compared to healthy controls. Also, the level in new-onset SLE patients was lower than that in inactive SLE patients [0.482(0.398, 0.512)] (p = 0.001). 3. Negative correlation was found between miR 326 and Ets-1 mRNA expression in Treg cells from new-onset SLE patients (r = 0.583 p = 0.01). 4. There was no correlation of miR-326 or Ets-1 mRNA expression with SLEDAI. The increase of miR-326 expression in Treg cells from SLE patients may inhibit the expression of Ets-1 to participate in the pathological process of SLE. PMID- 26861135 TI - Different Expression of MicroRNA-146a in Peripheral Blood CD4(+) T Cells and Lesions of Oral Lichen Planus. AB - Oral lichen planus (OLP) is a common T cell-mediated chronic inflammatory disease of unknown etiology. Recent increasing evidence indicates that microRNA-146a (miR 146a) plays a vital role in inflammatory diseases and T cell regulation. This study aimed to investigate the expression of miRNA-146a in peripheral blood CD4(+) T cells and local OLP lesions and to evaluate its relationship with clinical forms of OLP. Sixteen patients with OLP were divided into two groups: erosive OLP and nonerosive OLP. The expression of miR-146a was examined by quantitative real-time polymerase chain reaction. The expression of miR-146a in peripheral blood CD4(+) T cells showed no significant difference between OLP group and control group (P > 0.05), and among erosive OLP, nonerosive OLP, and control groups (P > 0.05 for all). The expression in local lesions of the OLP group was significantly higher than that of the control group (P = 0.003), and it was significantly higher in the erosive OLP group than in the non-erosive OLP (P = 0.010) and control groups (P = 0.007). However, miR-146a expression in the nonerosive OLP group did not significantly differ from that in the control group (P > 0.05). These data indicate that miR-146a might be more involved in the local immune disorder of OLP. MiR-146a might be utilized as a candidate biomarker to estimate the severity of OLP. PMID- 26861137 TI - Mechanisms Underlying Adaptation to Life in Hydrogen Sulfide-Rich Environments. AB - Hydrogen sulfide (H2S) is a potent toxicant interfering with oxidative phosphorylation in mitochondria and creating extreme environmental conditions in aquatic ecosystems. The mechanistic basis of adaptation to perpetual exposure to H2S remains poorly understood. We investigated evolutionarily independent lineages of livebearing fishes that have colonized and adapted to springs rich in H2S and compared their genome-wide gene expression patterns with closely related lineages from adjacent, nonsulfidic streams. Significant differences in gene expression were uncovered between all sulfidic and nonsulfidic population pairs. Variation in the number of differentially expressed genes among population pairs corresponded to differences in divergence times and rates of gene flow, which is consistent with neutral drift driving a substantial portion of gene expression variation among populations. Accordingly, there was little evidence for convergent evolution shaping large-scale gene expression patterns among independent sulfide spring populations. Nonetheless, we identified a small number of genes that was consistently differentially expressed in the same direction in all sulfidic and nonsulfidic population pairs. Functional annotation of shared differentially expressed genes indicated upregulation of genes associated with enzymatic H2S detoxification and transport of oxidized sulfur species, oxidative phosphorylation, energy metabolism, and pathways involved in responses to oxidative stress. Overall, our results suggest that modification of processes associated with H2S detoxification and toxicity likely complement each other to mediate elevated H2S tolerance in sulfide spring fishes. Our analyses allow for the development of novel hypotheses about biochemical and physiological mechanisms of adaptation to extreme environments. PMID- 26861138 TI - 1H, 15N and 13C assignments of the N-terminal domain of the Mediator complex subunit MED26. AB - MED26 is a subunit of the Mediator, a very large complex involved in regulation of gene transcription by RNA Polymerase II. MED26 regulates the switch between initiation and elongation phases of the transcription. This function requires interaction of its N-terminal domain (NTD) with several protein partners implicated in transcriptional regulation. Molecular details of the structure and interaction mode of MED26 NTD would improve understanding of this complex regulation. As a first step towards structural characterization, sequence specific (1)H, (13)C and (15)N assignments for MED26 NTD was performed based on Nuclear Magnetic Resonance spectroscopy. TALOS+ analysis of the chemical shifts data revealed a domain solely composed of helices. Assignments will be further used to solve NMR structure and dynamics of MED26 NTD and investigate the molecular details of its interaction with protein partners. PMID- 26861136 TI - An Overlook to the Characteristics and Roles Played by Eotaxin Network in the Pathophysiology of Food Allergies: Allergic Asthma and Atopic Dermatitis. AB - Investigations revealed substantial parts accomplished by chemokines specifically eotaxins and their specific receptors. They are functionally involved in the modulation of the pathologic state of tissue inflammation which is as a result of allergic reactions. Chemokines as small proteins with approximately 8-10 kDa molecular weight are considered and fit in the bigger family of cytokines, containing basic heparin-binding polypeptide mediators. Chemokines actively interfere in the processes of selective, oriented leukocyte (including eosinophil) recruitment. As eminent from their name, more specifically, eotaxins are specialized for eosinophils' oriented locomotion toward allergic inflamed regions. To date, three members are defined for eotaxin subfamily as follows: eotaxin-1 (CCL11), eotaxin-2 (CCL24), and eotaxin-3 (CCL26), all of them bind to and activate CCR3 but have a low level of homology and appear to exhibit different physiological potentials. Allergy is described as a clinical state in which a pathologic hypersensitivity reaction is always initiated throughout an immunologic mechanism; similar to other immunologic reactions, an allergic reaction could also either be antibody or cell mediated. This type of allergic reactions occurs in all age groups and damages several different organs, having a significant impact on the emotional and social health of patients and their families and relatives. Concerning introductory comments introduced above, the authors of the present review attempted to collect and provide the latest evidences and information regarding the correlation between expression of eotaxin family members and allergy, in a wider extent, in two important allergic disorders: atopic asthma (AA) and atopic dermatitis (AD). Overall, concerning the most recent articles published within the database in the life sciences literature regarding the fundamental role(s) played by eotaxins in the pathogenesis of AA and AD, the authors of the current article propose that eotaxins (CCL11, CCL24, and CCL26) play key role(s) during symptomatic inflammatory responses raised in response to allergic crisis of these two clinical states. PMID- 26861140 TI - Connecting heart failure with preserved ejection fraction and renal dysfunction: the role of endothelial dysfunction and inflammation. AB - Renal dysfunction in heart failure with preserved ejection fraction (HFpEF) is common and is associated with increased mortality. Impaired renal function is also a risk factor for developing HFpEF. A new paradigm for HFpEF, proposing a sequence of events leading to myocardial remodelling and dysfunction in HFpEF, was recently introduced, involving inflammatory, microvascular, and cardiac components. The kidney might play a key role in this systemic process. Renal impairment causes metabolic and systemic derangements in circulating factors, causing an activated systemic inflammatory state and endothelial dysfunction, which may lead to cardiomyocyte stiffening, hypertrophy, and interstitial fibrosis via cross-talk between the endothelium and cardiomyocyte compartments. Here, we review the role of endothelial dysfunction and inflammation to explain the link between renal dysfunction and HFpEF, which allows for identification of new early risk markers, prognostic factors, and unique targets for intervention. PMID- 26861139 TI - Increase in Fracture Risk Following Unintentional Weight Loss in Postmenopausal Women: The Global Longitudinal Study of Osteoporosis in Women. AB - Increased fracture risk has been associated with weight loss in postmenopausal women, but the time course over which this occurs has not been established. The aim of this study was to examine the effects of unintentional weight loss of >=10 lb (4.5 kg) in postmenopausal women on fracture risk at multiple sites up to 5 years after weight loss. Using data from the Global Longitudinal Study of Osteoporosis in Women (GLOW), we analyzed the relationships between self-reported unintentional weight loss of >=10 lb at baseline, year 2, or year 3 and incident clinical fracture in the years after weight loss. Complete data were available in 40,179 women (mean age +/- SD 68 +/- 8.3 years). Five-year cumulative fracture rate was estimated using the Kaplan-Meier method, and adjusted hazard ratios for weight loss as a time-varying covariate were calculated from Cox multiple regression models. Unintentional weight loss at baseline was associated with a significantly increased risk of fracture of the clavicle, wrist, spine, rib, hip, and pelvis for up to 5 years after weight loss. Adjusted hazard ratios showed a significant association between unintentional weight loss and fracture of the hip, spine, and clavicle within 1 year of weight loss, and these associations were still present at 5 years. These findings demonstrate increased fracture risk at several sites after unintentional weight loss in postmenopausal women. This increase is found as early as 1 year after weight loss, emphasizing the need for prompt fracture risk assessment and appropriate management to reduce fracture risk in this population. (c) 2016 American Society for Bone and Mineral Research. PMID- 26861141 TI - Flexible visiting positively impacted on patients, families and staff in an Australian Intensive Care Unit: A before-after mixed method study. AB - BACKGROUND: The admission of a relative to intensive care is stressful for families. To help them support the patient, families need assurance, information and an ability to be near their sick relative. Flexible visiting enables patient access but the impact of this on patients, families and staff is not clear. OBJECTIVE: To assess the impact of flexible visiting from the perspective of patients, families, and Intensive Care Unit (ICU) staff. METHODS: A before-after mixed method study was used with interviews, focus groups and surveys. Patients were interviewed, family members completed the Family Satisfaction in ICU survey and ICU staff completed a survey and participated in focus groups following the introduction of 21h per day visiting in a tertiary ICU. The study was conducted within a philosophy of family-centred care. RESULTS: All interviewed patients (n=12) positively evaluated the concept of extended visiting hours. Family members' (n=181) overall 'satisfaction with care' did not change; however 85% were 'very satisfied' with increased visiting flexibility. Seventy-six percent of family visits continued to occur within the previous visiting hours (11am-8pm) with the remaining 24% taking place during the newly available visiting hours. Families recognised the priority of patient care with their personal needs being secondary. Three-quarters of ICU staff were 'satisfied' with flexible visiting and suggested any barriers could be overcome by role modelling family inclusion. CONCLUSION: Patients, families and ICU staff positively evaluated flexible visiting hours in this ICU. Although only a minority of families took advantage of the increased hours they indicated appreciation for the additional opportunities. Junior staff may benefit from peer-support to develop family inclusion skills. More flexible visiting times can be incorporated into usual ICU practice in a manner that is viewed positively by all stakeholders. PMID- 26861142 TI - Evaluation of the site specificity of acute disuse muscle atrophy developed during a relatively short period in critically ill patients according to the activities of daily living level: A prospective observational study. AB - INTRODUCTION: In critically ill patients, excessive bed rest and immobilisation have been shown to cause disuse muscle atrophy, which contributes to prolonged hospitalisation and decreased activity of daily living (ADL) levels. However, the degree and site specificity of acute disuse muscle atrophy in critically ill patients during a relatively short intensive care unit (ICU) stay have not been fully elucidated. METHODS: Critically ill patients, who required bed rest on ICU admission, were eligible for this study. The degree of skeletal muscle atrophy was evaluated on the day of, and 72 and 144h after ICU admission by measuring the limb circumference in ADL-dependent or -independent patients separately at five different sites: the midpoint of the upper limb between the acromion and the olecranon, the maximum diameter of the triceps surae in the lower leg, and three different sites in the thigh at 5, 10, and 15cm above the superior pole of the patella. Value of the limb circumference was presented as a percentage relative to the baseline (median). RESULTS: In ADL-dependent patients, limb circumferences at all five sites were decreased significantly at 144h compared with the baseline (98.9-100% in the upper limbs, 97.1-97.2% in the lower legs, and 96.5-99.1% in the thighs), but not at 72h. In contrast, the limb circumferences at almost all sites decreased significantly at both 72 and 144h (100% in the upper limbs, 94.5 94.7% in the lower legs, and 89.7-94.7% in the thighs), compared with the baseline in ADL-independent patients. Muscle atrophy was greater at the four different lower-limb sites compared to the upper limb during 144h in the ICU in the ADL-independent, but not in the ADL-dependent patients. CONCLUSIONS: Compared to ADL-dependent patients, ADL-independent patients are prone to develop muscle weakness, especially in the lower limbs. PMID- 26861144 TI - Erratum. PMID- 26861143 TI - A Functional Vesicular Monoamine Transporter 1 (VMAT1) Gene Variant Is Associated with Affect and the Prevalence of Anxiety, Affective, and Alcohol Use Disorders in a Longitudinal Population-Representative Birth Cohort Study. AB - BACKGROUND: Inter-individual differences in the monoaminergic systems have been shown to moderate the risk for a lifetime history of anxiety, affective, and alcohol use disorders. A common single nucleotide polymorphism in the vesicular monoamine transporter 1 gene (VMAT1 rs1390938 G/A; Thr136Ile) has been reported as functional in vitro and associated with bipolar disorder and anxiety. We aimed at assessing the association between the VMAT1 genotype, affect, and affect related psychiatric disorders in a longitudinal population-representative study. METHODS: We used the database of the Estonian Children Personality Behaviour and Health Study (beginning in 1998). Cohorts of initially 9- (recalled at ages 15 and 18 years, n=579) and 15- (recalled at ages 18 and 25 years; n=654) year-old children provided self-reports on impulsivity, anxiety, depressiveness, neuroticism, and alcohol use. In addition, psychiatric assessment based on DSM-IV was carried out in the older cohort at age 25 years. RESULTS: Subjects homozygous for the less prevalent A (136Ile) allele reported lower maladaptive impulsivity, state and trait anxiety, depressiveness, and neuroticism and were less likely to have been diagnosed with an affective, anxiety, and/or alcohol use disorder by young adulthood. While in the younger cohort alcohol use started at younger age, this birth cohort effect was dependent on genotype: only G allele carriers and in particular the GG homozygotes started alcohol use earlier. CONCLUSIONS: VMAT1 rs1390938/Thr136Ile is associated with mood, personality, and alcohol use in the general population. Subjects homozygous for the "hyperfunction" allele (AA; Ile/Ile) appear to be more resilient to these disorders. PMID- 26861145 TI - Emotional Impairment and Persistent Upregulation of mGlu5 Receptor following Morphine Abstinence: Implications of an mGlu5-MOPr Interaction. AB - BACKGROUND: A difficult problem in treating opioid addicts is the maintenance of a drug-free state because of the negative emotional symptoms associated with withdrawal, which may trigger relapse. Several lines of evidence suggest a role for the metabotropic glutamate receptor 5 in opioid addiction; however, its involvement during opioid withdrawal is not clear. METHODS: Mice were treated with a 7-day escalating-dose morphine administration paradigm. Following withdrawal, the development of affective behaviors was assessed using the 3 chambered box, open-field, elevated plus-maze and forced-swim tests. Metabotropic glutamate receptor 5 autoradiographic binding was performed in mouse brains undergoing chronic morphine treatment and 7 days withdrawal. Moreover, since there is evidence showing direct effects of opioid drugs on the metabotropic glutamate receptor 5 system, the presence of an metabotropic glutamate receptor 5/MU-opioid receptor interaction was assessed by performing metabotropic glutamate receptor 5 autoradiographic binding in brains of mice lacking the MU opioid receptor gene. RESULTS: Withdrawal from chronic morphine administration induced anxiety-like, depressive-like, and impaired sociability behaviors concomitant with a marked upregulation of metabotropic glutamate receptor 5 binding. Administration of the metabotropic glutamate receptor 5 antagonist, 3 ((2-Methyl-4-thiazolyl)ethynyl)pyridine, reversed morphine abstinence-induced depressive-like behaviors. A brain region-specific increase in metabotropic glutamate receptor 5 binding was observed in the nucleus accumbens shell, thalamus, hypothalamus, and amygdala of MU-opioid receptor knockout mice compared with controls. CONCLUSIONS: These results suggest an association between metabotropic glutamate receptor 5 alterations and the emergence of opioid withdrawal-related affective behaviors. This study supports metabotropic glutamate receptor 5 system as a target for the development of pharmacotherapies for the treatment of opioid addiction. Moreover, our data show direct effects of MU-opioid receptor system manipulation on metabotropic glutamate receptor 5 binding in the brain. PMID- 26861147 TI - Ultrasound-guided popliteal sciatic nerve blockade in the severely and morbidly obese: a prospective and randomized study. AB - PURPOSE: Limited research data exist regarding optimal block techniques in the severely and morbidly obese patient population. We compared two approaches to sciatic nerve blockade at the popliteal fossa in severely and morbidly obese patients. The purpose of this study was to identify differences in pain scores, block onset characteristics, and adverse events between the proximal (prebifurcation) and the distal (postbifurcation) sites. METHODS: Patients with a body mass index >=35 scheduled for unilateral foot surgery with a popliteal block were randomized to receive an ultrasound-guided popliteal block proximal or distal to the bifurcation of the sciatic nerve. The primary endpoint was numerical rating scale (NRS) scores in the post anesthesia care unit (PACU). RESULTS: Thirty patients were enrolled in each group for a total of 60 participants. Patients in the distal group had lower NRS scores upon entry into the PACU (0.70 +/- 1.91) compared with the proximal group (2.17 +/- 3.37), had a faster onset of sensorimotor blockade, and were less likely to require a repeat block procedure, conversion to general anesthesia, or local anesthetic supplementation by the surgical team. There was no difference in block procedure times or incidence of nerve injury between the two groups. CONCLUSIONS: The distal approach to the popliteal block provided several intraoperative and analgesic benefits without a difference in block procedural times in the severely and morbidly obese. It is a cost-free intervention that results in a higher likelihood of a successful block in a population where avoidance of opioids is desirable. PMID- 26861146 TI - Enrichment analysis of Alu elements with different spatial chromatin proximity in the human genome. AB - Transposable elements (TEs) have no longer been totally considered as "junk DNA" for quite a time since the continual discoveries of their multifunctional roles in eukaryote genomes. As one of the most important and abundant TEs that still active in human genome, Alu, a SINE family, has demonstrated its indispensable regulatory functions at sequence level, but its spatial roles are still unclear. Technologies based on 3C (chromosome conformation capture) have revealed the mysterious three-dimensional structure of chromatin, and make it possible to study the distal chromatin interaction in the genome. To find the role TE playing in distal regulation in human genome, we compiled the new released Hi-C data, TE annotation, histone marker annotations, and the genome-wide methylation data to operate correlation analysis, and found that the density of Alu elements showed a strong positive correlation with the level of chromatin interactions (hESC: r = 0.9, P < 2.2 * 10(16); IMR90 fibroblasts: r = 0.94, P < 2.2 * 10(16)) and also have a significant positive correlation with some remote functional DNA elements like enhancers and promoters (Enhancer: hESC: r = 0.997, P = 2.3 * 10(-4); IMR90: r = 0.934, P = 2 * 10(-2); Promoter: hESC: r = 0.995, P = 3.8 * 10(-4); IMR90: r = 0.996, P = 3.2 * 10(-4)). Further investigation involving GC content and methylation status showed the GC content of Alu covered sequences shared a similar pattern with that of the overall sequence, suggesting that Alu elements also function as the GC nucleotide and CpG site provider. In all, our results suggest that the Alu elements may act as an alternative parameter to evaluate the Hi-C data, which is confirmed by the correlation analysis of Alu elements and histone markers. Moreover, the GC-rich Alu sequence can bring high GC content and methylation flexibility to the regions with more distal chromatin contact, regulating the transcription of tissue-specific genes. PMID- 26861148 TI - MiR-502-5p inhibits IL-1beta-induced chondrocyte injury by targeting TRAF2. AB - Osteoarthritis (OA) is characterized by articular cartilage degradation and joint inflammation. MicroRNAs have been proven to play an important role in the regulation of chondrogenesis. The aim of the present study was to investigate the effect of miR-502-5p in OA. The results showed that miR-502-5p levels were significantly down-regulated in OA articular tissues and IL-1beta-induced chondrocytes compared with control groups. MiR-502-5p overexpression inhibited IL 1beta-induced reduction in cell viability and increase in cell apoptosis, and alleviated IL-1beta-induced extracellular matrix (ECM) metabolic imbalance and pro-inflammatory cytokine production. MiR-502-5p targeted the 3'-untranslated region (UTR) of TRAF2 to inhibit its expression. The IL-1beta-induced activation of NF-kappaB signaling pathway was inhibited by PDTC, an inhibitor of NF-kappaB, which was also suppressed by the miR-502-5p mimic and TRAF2 siRNA transfection. In conclusion, miR-502-5p may exhibit a protective effect on IL-1beta-induced chondrocyte injury by targeting TRAF2 and inhibiting NF-kappaB signaling pathway. PMID- 26861150 TI - Steered molecular dynamics study reveals insights into the function of the repetitive B region of collagen- and fibrinogen-binding MSCRAMMs. AB - MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) are modular proteins covalently anchored in the bacterial cell wall of many Gram positive bacteria. The N-terminal region of most MSCRAMMs carries the ligand binding domains (A region) which specifically target the host extracellular matrix (ECM) proteins such as collagen, fibrinogen and fibronectin. In Staphylococcus aureus Cna, the prototype collagen-binding MSCRAMM, the A region is followed by a repetitive B region which is found to be conserved among many Gram-positive bacteria. This conservation signifies an important functional role for the B region which is made of repetitive domains. It was suggested that this region could act as a 'stalk' as well as a 'spring' to present the ligand-binding A region, away from the bacterial surface. But there is no clear functional implication of this region available till date. Each repetitive domain in the B region possesses a variant of the Ig fold called the CnaB fold. Additionally, the B repeats are also paired and the pairs are clustered together. To investigate if the B domains have a function similar to the Ig domains in the I-band region of the giant muscle protein, titin, steered molecular dynamics simulations of one, two and four B repeats of Cna were carried out. The results of the simulations suggest that the B region could provide mechanical stability, extensibility and elasticity to Cna due to the CnaB fold as well as the clustered arrangement of their domains. This study thus provided further insights into the biological underpinnings of adhesin-host interaction. PMID- 26861149 TI - The best objective response of target lesions and the incidence of treatment related hypertension are associated with the survival of patients with metastatic renal cell carcinoma treated with sunitinib: a Japanese retrospective study. AB - BACKGROUND: The aim of this study is to investigate the prognostic relevance of the best objective response of metastatic target lesions during sunitinib treatment in patients with metastatic renal cell carcinoma. METHODS: Radiographic analysis of the best objective response according to the Response Evaluation Criteria in Solid Tumors was assessed in 50 patients. Clinicopathological characteristics including the Heng risk classification and sunitinib-related adverse reactions were compared among four patient subgroups [complete response or partial response (CR/PR), stable disease (SD), progressive disease (PD), and those without treatment evaluation (NE)]. Kaplan-Meier and Cox proportional regression analyses of progression-free survival and overall survival were performed to identify prognostic variables. RESULTS: The best objective response was CR/PR in 12 (24 %) patients, SD in 22 (44 %), PD in 6 (12 %), and NE in 10 (20 %). The incidence of hypertension and hypothyroidism was associated with a better objective response. Progression-free survival was 15.0, 9.2, 6.8, and 2.2 months in the CR/PR, SD, PD, and NE groups, respectively (P = 0.0004, log-rank test), while the corresponding median overall survival was 59.7, 24.2, 17.1, and 18.1 months, respectively (P = 0.007). Multivariate analysis revealed that hazard ratios for risk of death of the SD, PD, and NE groups were 4.51 (P = 0.06), 7.93 (P = 0.02), and 4.88 (P = 0.04), respectively, as compared to the CR/PR group. CONCLUSIONS: Our findings suggested that the best objective response of target lesions was a prognostic marker for both progression-free survival and overall survival in sunitinib treatment. Furthermore, the incidence of sunitinib-induced hypertension was associated with a longer progression-free survival. PMID- 26861152 TI - Erratum to: Do Orthopaedic Surgeons Acknowledge Uncertainty? PMID- 26861151 TI - CORR Insights((r)): Biofilm Antimicrobial Susceptibility Increases With Antimicrobial Exposure Time. PMID- 26861153 TI - The Effect of a Non-Powered, Self-Initiated Mobility Program on the Engagement of Young Children with Severe Mobility Limitations in the South African Context. AB - AIM: To determine the effect of a non-powered, self-initiated mobility program on the engagement of young children with severe mobility limitations, in the South African context. METHODS: A multiple-probe-across-participant design was used. Four children (aged 2-6 years) with severe mobility limitations underwent an intervention that targeted non-powered, self-initiated mobility. The intervention comprised eight sessions over a 2-week period. Engagement was measured during each baseline, intervention and postintervention session using the Individual Child Engagement Record-Revised (ICER-R). The data were presented graphically and analyzed using statistical procedures appropriate for single-subject designs. RESULTS: Participants demonstrated an improvement in engagement during the time in which non-powered, self-initiated mobility program was introduced. A reciprocal deterioration in nonengagement was also demonstrated. The results of the study are discussed in terms of various intrinsic and extrinsic factors. CONCLUSIONS: The use of a non-powered, self-initiated mobility program may be effective in improving engagement in some young children with severe mobility limitations. PMID- 26861155 TI - Incidental findings in population imaging revisited. PMID- 26861154 TI - Reported associations between asthma and acute lymphoblastic leukemia: insights from a hybrid simulation study. AB - Numerous studies have reported a protective association between asthma and acute lymphoblastic leukemia (ALL), but the causal structure of this association remains unclear. We present a hybrid simulation to examine the compatibility of this association with uncontrolled confounding by infection or another unmeasured factor. We generated a synthetic cohort using inputs on the interrelations of asthma, ALL, infections, and other suggested risk factors from the literature and the Danish National Birth Cohort. We computed odds ratios (ORs) between asthma and ALL in the synthetic cohort with and without adjustment for infections and other (including unmeasured) confounders. Only if infection was an extremely strong risk factor for asthma (OR of 10) and an extremely strong protective factor against ALL (OR of 0.1) was the asthma-ALL association compatible with the literature (OR of 0.78). Similarly, strong uncontrolled confounding by an unmeasured factor could downwardly bias the asthma-ALL association, but not enough to replicate findings in the literature. This investigation illustrates that the reported protective association between asthma and ALL is unlikely to be entirely due to uncontrolled confounding by infections or an unmeasured confounder alone. Simulation can be used to advance our understanding of risk factors for rare outcomes as demonstrated by this study. PMID- 26861157 TI - Polyunsaturated Fatty Acids Are Associated With Behavior But Not With Cognition in Children With and Without ADHD: An Italian study. AB - OBJECTIVE: This study aimed to investigate the relationship between polyunsaturated fatty acids (PUFAs) status, cognitive, and behavioral traits of ADHD in school-aged children. METHOD: Seventy-three children with and without ADHD were assessed with cognitive tasks and behavioral rating scales including quality of life and global functioning at baseline of an intervention trial (clinicaltrials.gov NCT01796262). Correlation analyses were performed between the cognitive tasks/behavioral ratings and blood PUFA levels. RESULTS: Children with ADHD had lower levels of DHA, omega-3 index, and total PUFA. PUFAs were positively associated with behavior but not consistently related to cognitive domains. CONCLUSION: The present study confirms that children with ADHD display abnormal fatty acid profiles within an Italian setting. Furthermore, PUFAs were associated with behavior but not with cognition. Accordingly, for the first time, lower blood levels of PUFA were associated not only with symptoms of ADHD but also with a poorer quality of life. PMID- 26861158 TI - The Effects of Physical Exercise on Functional Outcomes in the Treatment of ADHD: A Meta-Analysis. AB - OBJECTIVE: An increasing number of studies suggest possible beneficial effects of exercise in alleviating ADHD functional outcomes. The current study provides a quantitative meta-analysis of the available studies investigating this relationship. METHOD: Studies reporting on the effects of physical exercise on motor skills and executive functions in children with ADHD were identified through Cochrane, PsycInfo, PubMed, Web of Science databases. Ten publications were selected. Random-effects model was used to calculate effect sizes. RESULTS: There was a significant effect of exercise on ADHD functional outcomes (g = 0.627). Longer exercise intervention duration was consistently associated with larger effect sizes. Effect sizes were not related to exercise intensity, mean age of participants, or gender distribution. CONCLUSION: Results suggest that exercise has a modest positive impact on ADHD functional outcomes, such as executive functions and motor skills, with longer interventions yielding better results. PMID- 26861156 TI - Test-Retest Reliability and Measurement Invariance of Executive Function Tasks in Young Children With and Without ADHD. AB - OBJECTIVE: Measurement reliability is assumed when executive function (EF) tasks are used to compare groups or to examine relationships between cognition and etiologic and maintaining factors of psychiatric disorders. However, the test retest reliabilities of many commonly used EF tasks have rarely been examined in young children. Furthermore, measurement invariance between typically developing and psychiatric populations has not been examined. METHOD: Test-retest reliability of a battery of commonly used EF tasks was assessed in a group of children between the ages of 5 and 6 years old with (n = 63) and without (n = 44) ADHD. RESULTS: Few individual tasks achieved adequate reliability. However, confirmatory factor analysis (CFA) models identified two factors, working memory and inhibition, with test-retest correlations approaching 1.0. Multiple indicators multiple causes (MIMIC) models confirmed configural measurement invariance between the groups. CONCLUSION: Problems created by poor reliability, including reduced power to detect group differences, index change over time, or to identify relationships with other measures, may be mitigated using latent variable approaches. PMID- 26861159 TI - Elevated VEGFA mRNA levels in oral squamous cell carcinomas and tumor margins: a preliminary study. AB - BACKGROUND: New blood vessel formation events are essential for tumor clonal expansion and progression. Despite the importance of vascular endothelial growth factor A (VEGFA) for tumor angiogenesis, few studies have evaluated the expression profile of this gene in oral squamous cell carcinoma (OSCC) and tumor margins (TM). This study aimed to evaluate the expression of the VEGFA gene and its protein in OSCC and TM. METHODS: Gene expression was evaluated in cryopreserved samples of OSCCs (n = 44), TM (n = 7), and normal mucosa from healthy patients (n = 3; NM). Quantitative PCRs were performed using the TaqMan system for the VEGFA gene, and gene expression was determined using the 2(-??CQ) method. For immunohistochemical evaluation, 27 OSCC samples were embedded in a tissue microarray (TMA) block and reactions were performed using the Advance system. RESULTS: VEGFA transcript levels were 1.7-fold higher in OSCC than in NM samples. VEGFA mRNA was overexpressed in TM samples compared to NM (3.4-fold) and OSCC (2.0-fold) samples. VEGFA transcript level was overexpressed in T3-T4 tumors, metastatic lymph nodes, and stage III-IV OSCCs. Immunoreactivity of the VEGFA protein was detected in the cytoplasm of parenchymal and stromal cells, mainly in endothelial cells and fibroblasts. CONCLUSION: Our results show that VEGFA was overexpressed in aggressive OSCCs and that VEGFA expression may be an important prognostic factor in this type of cancer. Finally, tumor margins may be involved in the production of angiogenic molecules. PMID- 26861160 TI - The advantages of tomosynthesis for evaluating bisphosphonate-related atypical femur fractures compared to radiography. AB - OBJECTIVE: To investigate the advantages of using tomosynthesis (TS) compared to radiographs in the detection, characterization, and follow-up of bisphosphonate related atypical femur fractures (BP-AFF). SUBJECTS AND METHODS: Eight patients were identified retrospectively who underwent TS for radiographic findings suspicious for BP-AFF. Two radiologists independently interpreted 15 radiographs and 16 TS examinations, indicating the presence or absence of the following: (1) cortical "beaking" on radiographs, (2) radiolucent fracture line on radiographs, and (3) fracture lucency on TS corresponding to the site of radiographic abnormality. Radiation dose data were calculated for radiographs and TS using Monte Carlo analysis. RESULTS: There was agreement on 100 % of radiographs regarding the presence or absence of a cortical beak. Regarding the presence or absence of a fracture lucency, there was agreement on 100 % of TS examinations (Kappa = 1.0) and 73 % of radiographs (Kappa = 0.40 +/- 0.24). For the 46 % of radiographs in which one or both radiologists did not visualize a fracture line, there was 100 % agreement for the presence of a fracture line on the corresponding TS. The interobserver agreement for fracture line detection was significantly higher for TS than for radiographs (p = 0.012). The effective radiation dose using TS was approximately 96 % lower compared to radiography. CONCLUSION: TS outperformed radiographs in the detection and characterization of BP-AFF. TS may also have advantages over radiography for BP-AFF follow-up through its unique ability to visualize fracture healing with lower effective radiation doses to the patient. PMID- 26861161 TI - Sonographic evaluation of athletic pubalgia. AB - Athletic pubalgia, or "sports hernia", represents a constellation of pathologic conditions occurring at and around the pubic symphysis. These injuries are primarily seen in athletes or those involved in athletic activity. In this article, we review the sonographic appearance of the relevant complex anatomy, scanning technique for ultrasound evaluation of athletic pubalgia, and the sonographic appearances of associated pathologic conditions. PMID- 26861163 TI - Podosome Formation and Development in Monocytes Restricted by the Nanoscale Spatial Distribution of ICAM1. AB - We studied podosome formation and development in activated monocytes (THP1) at ICAM1 (intercellular adhesion molecule 1) nanopatterns of circular and ring shaped domains and show that cellular binding to a preclustered ICAM1 nanopattern requires ligand patches of at least 200 nm (corresponding to 14 or more integrins). Podosome-like adhesion formation depends on the structure of the ligand pattern under the developing podosome with larger single domains promoting adhesion in a single patch and multiple smaller domains allowing podosome formation by integration of at least 2 smaller domains on either side of the podosome core. Maturation to rosette structures and recruitment of proteases were only observed with macroscopic ICAM1 presentation. PMID- 26861162 TI - Predictors of metabolic abnormalities in phenotypes that combined anthropometric indices and triglycerides. AB - BACKGROUND: The hypertriglyceridemic waist (HW) phenotype has been shown to be strongly associated with metabolic abnormalities; however, to date, no study has reported the prediction of metabolic abnormalities using the HW phenotype along with waist circumference (WC) and the triglyceride (TG) level or various phenotypes consisting of an individual anthropometric index combined with the TG level. The objectives of this study were to assess the association of the HW phenotype with metabolic abnormalities in Korean women and to evaluate the predictive powers of various phenotypes with regard to metabolic abnormalities. METHODS: Total cholesterol (TC), high- and low-density lipoprotein (HDL and LDL) cholesterol, and TG levels, systolic and diastolic blood pressures (SBP and DBP), and anthropometric indices were measured in 7661 women. The Naive Bayes algorithm and logistic regression were used to determine the predictive powers of the models using different phenotypes. RESULTS: The HW phenotype demonstrated the strongest association with all metabolic components. The best phenotypic predictors were the forehead-to-rib circumference ratio + TG for the HDL level, age + TG for the LDL level, age + TG for SBP, and rib circumference + TG and neck circumference + TG for DBP. The associations between TG and TC or HDL were higher compared with those between WC and TC or HDL, whereas the associations between WC and SBP or DBP were higher compared with those between TG and SBP or DBP. Age was strongly associated with hypercholesterolemia, the HDL and LDL cholesterol levels, and SBP and had good predictive power, but not with respect to DBP. CONCLUSIONS: We have determined that the HW phenotype is a useful indicator of metabolic abnormalities in Korean women; although HW had the strongest association with metabolic abnormalities, the best phenotype combination consisting of a single anthropometric index and the TG level may differ depending on the metabolic factors in question. Our findings provide insights into the detection of metabolic abnormalities in complementary and alternative medicine. PMID- 26861165 TI - Changes in the medical management of patients on opioid analgesics following a diagnosis of substance abuse. AB - PURPOSE: When providers recognize that patients are abusing prescription drugs, review of the drugs they are prescribed and attempts to treat the substance use disorder are warranted. However, little is known about whether prescribing patterns change following such a diagnosis. METHODS: We used national longitudinal health claims data from the Market Scan(r) commercial claims database for January 2010-June 2011. We used a cohort of 1.85 million adults 18 64 years old prescribed opioid analgesics but without abuse diagnoses during a 6 month "preabuse" period. We identified a subset of 9009 patients receiving diagnoses of abuse of non-illicit drugs (abuse group) during a 6-month "abuse" period and compared them with patients without such a diagnosis (nonabuse group) during both the abuse period and a subsequent 6-month "postabuse" period. RESULTS: During the abuse period 5.78% of the abuse group and 0.14% of the nonabuse group overdosed. Overdose rates declined to 2.12% in the abuse group in the postabuse period. Opioid prescribing rates declined 13.5%, and benzodiazepine rates declined 12.3% in the abuse group in the post-abuse period. Antidepressants and gabapentin were prescribed to roughly one half and one quarter of the abuse group, respectively, during all three periods. Daily opioid dosage did not decline in the abuse group following diagnosis. CONCLUSIONS: Prescribing to people who abuse drugs changes little after their abuse is documented. Actions such as tapering opioid and benzodiazepine prescriptions, maximizing alternative treatments for pain, and greater use of medication-assisted treatment such as buprenorphine could help reduce risk in this population. Published 2016. This article is a U.S. Government work and is in the public domain in the USA. PMID- 26861164 TI - Teaching neurons to respond to placebos. AB - KEY POINTS: We analysed the placebo response at the single-neuron level in the thalamus of Parkinson patients to see the differences between first-time administration of placebo and administration after pharmacological pre conditioning. When the placebo was given for the first time, it induced neither clinical improvement, as assessed through muscle rigidity reduction at the wrist, nor neuronal changes in thalamic neurons. However, if placebo was given after two, three or four prior administrations of an anti-Parkinson drug, apomorphine, it produced both clinical and neuronal responses. Both the magnitude and the duration of these placebo responses depended on the number of prior exposures to apomorphine, according to the rule: the greater the number of previous apomorphine administrations, the larger the magnitude and the longer the duration of the clinical and neuronal placebo responses. These findings show that learning plays a crucial role in the placebo response and suggest that placebo non responders can be turned into placebo responders, with important clinical implications. ABSTRACT: Placebos have been found to affect the patient's brain in several conditions, such as pain and motor disorders. For example, in Parkinson's disease, a placebo treatment induces a release of dopamine in the striatum and changes the activity of neurons in both thalamic and subthalamic nuclei. The present study shows that placebo administration for the first time induces neither clinical nor neuronal improvement in Parkinson patients who undergo implantation of electrodes for deep brain stimulation. However, this lack of placebo responsiveness can be turned into substantial placebo responses following previous exposure to repeated administrations of the anti-Parkinson agent apomorphine. As the number of apomorphine administrations increased from one to four, both the clinical response and the neuronal activity in the ventral anterior and anterior ventrolateral thalamus increased. In fact, after four apomorphine exposures, placebo administration induced clinical responses that were as large as those to apomorphine, along with long-lasting neuronal changes. These clinical placebo responses following four apomorphine administrations were again elicited after a re-exposure to a placebo 24 h after surgery, but not after 48 h. These data indicate that learning plays a crucial role in placebo responsiveness and suggest that placebo non-responders can be turned into responders, with important implications in the clinical setting. PMID- 26861167 TI - Altered brain activation in complex walking conditions in patients with Parkinson's disease. AB - INTRODUCTION: Behavioral studies suggest that deficits in cognitive domains and sensory-motor processes associated with Parkinson's disease (PD) impair the ability to walk in complex environments. However, the neural correlates of locomotion in complex environments are still unclear. METHODS: Twenty healthy older adults (mean age 69.7 +/- 1.3 yrs) and 20 patients with PD (mean age 72.9 +/- 1.6 yrs; disease duration: 6.8 +/- 1.3 yrs; UPDRSIII: 29.8 +/- 2.4) were asked to imagine themselves walking while in the MRI scanner. Three imagined walking tasks, i.e., usual walking, obstacle negotiation, and navigation were performed. Watching the same virtual scenes without imagining walking served as control tasks. Whole brain analyses were used. RESULTS: Compared to usual walking, both groups had increased activation during obstacle negotiation in middle occipital gyrus (MOG) (pFWEcorr<0.001), middle frontal gyrus (MFG) (pFWEcorr<0.005), and cerebellum (pFWEcorr<0.001). Healthy older adults had higher activation in precuneus and MOG (pFWEcorr<0.023) during navigation, while no differences were observed in patients with PD. Between group comparisons revealed that patients with PD had a significantly higher activation in usual walking and obstacle negotiation (pFWEcorr<0.039) while during navigation task, healthy older adults had higher activation (pFWEcorr<0.047). CONCLUSIONS: Patients with PD require greater activation during imagined usual walking and obstacle negotiation than healthy older adults. This increased activation may reflect a compensatory attempt to overcome inefficient neural activation in patients with PD. This increased activation may reduce the functional reserve needed during more demanding tasks such as during navigation which may contribute to the high prevalence of falls and dual tasking difficulties among patients with PD. PMID- 26861166 TI - Pragmatic pharmacology: population pharmacokinetic analysis of fentanyl using remnant samples from children after cardiac surgery. AB - AIMS: One barrier contributing to the lack of pharmacokinetic (PK) data in paediatric populations is the need for serial sampling. Analysis of clinically obtained specimens and data may overcome this barrier. To add evidence for the feasibility of this approach, we sought to determine PK parameters for fentanyl in children after cardiac surgery using specimens and data generated in the course of clinical care, without collecting additional blood samples. METHODS: We measured fentanyl concentrations in plasma from leftover clinically-obtained specimens in 130 paediatric cardiac surgery patients and successfully generated a PK dataset using drug dosing data extracted from electronic medical records. Using a population PK approach, we estimated PK parameters for this population, assessed model goodness-of-fit and internal model validation, and performed subset data analyses. Through simulation studies, we compared predicted fentanyl concentrations using model-driven weight-adjusted per kg vs. fixed per kg fentanyl dosing. RESULTS: Fentanyl clearance for a 6.4 kg child, the median weight in our cohort, is 5.7 l h(-1) (2.2-9.2 l h(-1) ), similar to values found in prior formal PK studies. Model assessment and subset analyses indicated the model adequately fit the data. Of the covariates studied, only weight significantly impacted fentanyl kinetics, but substantial inter-individual variability remained. In simulation studies, model-driven weight-adjusted per kg fentanyl dosing led to more consistent therapeutic fentanyl concentrations than fixed per kg dosing. CONCLUSIONS: We show here that population PK modelling using sparse remnant samples and electronic medical records data provides a powerful tool for assessment of drug kinetics and generation of individualized dosing regimens. PMID- 26861169 TI - Steroid-Responsive Encephalopathy, Dropped Head Syndrome, and Hypertension in a Toddler: Is There a Clue? AB - BACKGROUND: Paraneoplastic manifestations may provide an early clue to underlying malignancies in children. METHODS: We describe a 3-year-old girl with an unusual neurological paraneoplastic syndrome of steroid-responsive encephalopathy and dropped head syndrome associated with paraspinal neuroblastoma. RESULTS: Cranial neuroimaging, metabolic screen, and thyroid functions were normal. Abdominal imaging identified a paraspinal neuroblastoma. Encephalopathy and neck extensor weakness responded to pulse corticosteroids followed by tumor resection. CONCLUSIONS: This is a unique child with paraneoplastic steroid-responsive encephalopathy and dropped head syndrome in association with neuroblastoma. PMID- 26861168 TI - A toolbox of genes, proteins, metabolites and promoters for improving drought tolerance in soybean includes the metabolite coumestrol and stomatal development genes. AB - BACKGROUND: The purpose of this project was to identify metabolites, proteins, genes, and promoters associated with water stress responses in soybean. A number of these may serve as new targets for the biotechnological improvement of drought responses in soybean (Glycine max). RESULTS: We identified metabolites, proteins, and genes that are strongly up or down regulated during rapid water stress following removal from a hydroponics system. 163 metabolites showed significant changes during water stress in roots and 93 in leaves. The largest change was a root-specific 160-fold increase in the coumestan coumestrol making it a potential biomarker for drought and a promising target for improving drought responses. Previous reports suggest that coumestrol stimulates mycorrhizal colonization and under certain conditions mycorrhizal plants have improved drought tolerance. This suggests that coumestrol may be part of a call for help to the rhizobiome during stress. About 3,000 genes were strongly up-regulated by drought and we identified regulators such as ERF, MYB, NAC, bHLH, and WRKY transcription factors, receptor like kinases, and calcium signaling components as potential targets for soybean improvement as well as the jasmonate and abscisic acid biosynthetic genes JMT, LOX1, and ABA1. Drought stressed soybean leaves show reduced mRNA levels of stomatal development genes including FAMA-like, MUTE-like and SPEECHLESS-like bHLH transcription factors and leaves formed after drought stress had a reduction in stomatal density of 22.34 % and stomatal index of 17.56 %. This suggests that reducing stomatal density may improve drought tolerance. MEME analyses suggest that ABRE (CACGT/CG), CRT/DRE (CCGAC) and a novel GTGCnTGC/G element play roles in transcriptional activation and these could form components of synthetic promoters to drive expression of transgenes. Using transformed hairy roots, we validated the increase in promoter activity of GmWRKY17 and GmWRKY67 during dehydration and after 20 MUM ABA treatment. CONCLUSIONS: Our toolbox provides new targets and strategies for improving soybean drought tolerance and includes the coumestan coumestrol, transcription factors that regulate stomatal density, water stress-responsive WRKY gene promoters and a novel DNA element that appears to be enriched in water stress responsive promoters. PMID- 26861170 TI - Cyclic Vomiting Syndrome in Infants and Children: A Clinical Follow-Up Study. AB - BACKGROUND: Cyclic vomiting syndrome is characterized by recurrent vomiting that is associated with increased adrenocorticotropic hormone and antidiuretic hormone levels during cyclic vomiting syndrome attacks. However, both prognosis and treatment remain unclear. We therefore evaluated the clinical features, prognosis, and effectiveness of the prophylaxis of cyclic vomiting syndrome as well as the relationship between symptoms and adrenocorticotropic hormone/antidiuretic hormone levels. METHODS: We included 31 patients with cyclic vomiting syndrome who were admitted to Teikyo University between 1996 and 2008. All patients were diagnosed with cyclic vomiting syndrome based on the criteria of the second edition of the International Headache Classification. The patients (25 of 31) were followed until 2013. RESULTS: The median overall duration of the disorder was 66 (3-179) months. Follow-up was completed for 25 patients with cyclic vomiting syndrome, of whom 44% (n = 11) developed migraine. Valproic acid, valproic acid with phenobarbital, phenobarbital, and amitriptyline were effective in nine, four, three, and one patients, respectively. Abnormally high adrenocorticotropic hormone (n = 17) and antidiuretic hormone (n = 18) levels were found among the 25 patients for whom follow-up data were available. The following correlations were significant: attack duration and adrenocorticotropic hormone levels (correlation coefficient: 0.5153, P = 0.0084) and attack duration and antidiuretic hormone levels (correlation coefficient: 0.5666, P = 0.0031). Antidiuretic hormone levels in patients with bilious vomiting were higher than in those without bilious vomiting (P = 0.048). CONCLUSIONS: Most patients with cyclic vomiting syndrome recovered completely and benefited from prophylactic therapy, although half of them developed migraines. PMID- 26861171 TI - Polymerization stress evolution of a bulk-fill flowable composite under different compliances. AB - OBJECTIVE: To use a compliance-variable instrument to simultaneously measure and compare the polymerization stress (PS) evolution, degree of conversion (DC), and exotherm of a bulk-fill flowable composite to a packable composite. METHODS: A bulk-fill flowable composite (Filtek Bulk-fill, FBF) and a conventional packable composite (Filtek Z250, Z250) purchased from 3M ESPE were investigated. The composites were studied using a cantilever-beam based instrument equipped with an in situ near infrared (NIR) spectrometer and a microprobe thermocouple. The measurements were carried out under various instrumental compliances (ranging from 0.3327MUm/N to 12.3215MUm/N) that are comparable to the compliances of clinically prepared tooth cavities. Correlations between the PS and temperature change as well as the DC were interpreted. RESULTS: The maximum PS of both composites at 10min after irradiation decreased with the increase in the compliance of the cantilever beam. The FBF composite generated a lower final stress than the Z250 sample under instrumental compliances less than ca. 4MUm/N; however, both materials generated statistically similar PS values at higher compliances. The reaction exotherm and the DC of both materials were found to be independent of compliance. The DC of the FBF sample was slightly higher than that of the packable Z250 composite while the peak exotherm of FBF was almost double that of the Z250 composite. For FBF, a characteristic drop in the PS was observed during the early stage of polymerization for all compliances studied which was not observed in the Z250 sample. This drop was shown to relate to the greater exotherm of the less-filled FBF sample relative to the Z250 composite. SIGNIFICANCE: While the composites with lower filler content (low viscosity) are generally considered to have lower PS than the conventional packable composites, a bulk-fill flowable composite was shown to produce lower PS under a lower compliance of constraint as would be experienced if the composite was used as the base material in clinical procedures. PMID- 26861172 TI - Use of the reverse shock index for identifying high-risk patients in a five-level triage system. AB - BACKGROUND: The ratio of systolic blood pressure (SBP) to heart rate (HR), called the reverse shock index (RSI), is used to evaluate the hemodynamic stability of trauma patients. To minimize undertriage in emergency departments (EDs), we evaluated whether RSI < 1 (i.e., SBP lower than HR) could be used as an additional variable to identify patients at high risk for more severe injury within a level category of the five-level Taiwan Triage and Acuity Scales (TTAS) system. METHODS: Data obtained from the Trauma Registry System, including triage level according to the TTAS system, were retrospectively reviewed for trauma admissions from January 2009 through December 2013 in a Level I trauma center. In our study, the primary outcomes were injury severity as measured using different scoring systems, including the Glasgow coma scale (GCS), abbreviated injury scale scores, and the injury severity score (ISS), and in-hospital mortality. The secondary outcomes were hospital and intensive care unit (ICU) length of stay (LOS). RESULTS: Of 10,814 trauma patients, 348 patients (3.2%) had RSI < 1, whereas 10,466 (96.8%) had RSI >= 1. Those with RSI < 1 had greater injury severity, a higher incidence of commonly associated injuries, lower GCS scores, greater deterioration of vital signs, and a higher incidence of procedures those with RSI >= 1. Patients with RSI < 1 also worse outcomes including hospital and ICU LOS, a greater frequency of ICU admission, and higher in-hospital mortality. Although the five-level TTAS system provides good prioritization of patients with major trauma, using the additional criterion of RSI < 1 could identify the patients at higher risk within the same triage level (I-III). DISCUSSION: The alert of a trauma patient's SBP being lower than his/her HR (RSI < 1) without the requirement of any additional equipment makes the concept of RSI particularly valuable in crowded EDs for identifying high-risk patients. RSI < 1 may serve as a principle trigger for action in the ED to alert trauma surgeons to the need for early intervention and timely preparation upon patient arrival particularly for those patients triaged in levels II and III of the TTAS system. CONCLUSIONS: RSI < 1 upon arrival at an ED is an alarming sign of an associated worse outcome. Within the same triage level from level I to level III, patients with RSI < 1 had worse outcomes than those with RSI >= 1. The inclusion of RSI in the TTAS system may help to identify patients with more serious injuries who need an upgraded management level. PMID- 26861173 TI - SpyRing interrogation: analyzing how enzyme resilience can be achieved with phytase and distinct cyclization chemistries. AB - Enzymes catalyze reactions with exceptional selectivity and rate acceleration but are often limited by instability. Towards a generic route to thermo-resilience, we established the SpyRing approach, cyclizing enzymes by sandwiching between SpyTag and SpyCatcher (peptide and protein partners which lock together via a spontaneous isopeptide bond). Here we first investigated the basis for this resilience, comparing alternative reactive peptide/protein pairs we engineered from Gram-positive bacteria. Both SnoopRing and PilinRing cyclization gave dramatic enzyme resilience, but SpyRing cyclization was the best. Differential scanning calorimetry for each ring showed that cyclization did not inhibit unfolding of the inserted beta-lactamase. Cyclization conferred resilience even at 100 degrees C, where the cyclizing domains themselves were unfolded. Phytases hydrolyze phytic acid and improve dietary absorption of phosphate and essential metal ions, important for agriculture and with potential against human malnutrition. SpyRing phytase (PhyC) resisted aggregation and retained catalytic activity even following heating at 100 degrees C. In addition, SpyRing cyclization made it possible to purify phytase simply by heating the cell lysate, to drive aggregation of non-cyclized proteins. Cyclization via domains forming spontaneous isopeptide bonds is a general strategy to generate resilient enzymes and may extend the range of conditions for isolation and application of enzymes. PMID- 26861174 TI - phiXANES: In vivo imaging of metal-protein coordination environments. AB - We have developed an X-ray absorption near edge structure spectroscopy method using fluorescence detection for visualizing in vivo coordination environments of metals in biological specimens. This approach, which we term fluorescence imaging XANES (phiXANES), allows us to spatially depict metal-protein associations in a native, hydrated state whilst avoiding intrinsic chemical damage from radiation. This method was validated using iron-challenged Caenorhabditis elegans to observe marked alterations in redox environment. PMID- 26861176 TI - Sulfate-reducing bacteria impairs working memory in mice. AB - The ability of gut microbes to bi-directionally communicate with the brain and vice versa form the basis of the gut microbiome-central nervous system axis. It has been shown that inoculation with pathogenic gut bacteria alters the behavior of mice; however, it is not known whether or not non-pathogenic resident microbes have similar effects. In this study, we tested the hypothesis that the administration of sulfate-reducing bacteria (SRB), a specific group of resident gut bacteria that generate hydrogen sulfide (H2S), impair learning and memory performance in mice tested in an 8-arm radial maze and Morris water maze. We found that mice spent more time in the center of the maze when they were gavaged with live SRB as compared to mice given saline (control), lactulose+mannitol (L/M), or killed SRB. SRB-gavaged mice were also tested using the Morris water maze and were found to take longer to complete the test, spend more time further from the platform, and have a longer path length to reach the platform. This effect of SRB on maze performance was associated with a higher concentration of H2S in the small intestine and cecum. We conclude that SRB, a specific resident gut bacterial species, could impair cognitive function in mice. PMID- 26861175 TI - Creativity needs some serendipity: Reflections on a career in ingestive behavior. AB - I describe my 50year career in ingestive behavior in the hope of inspiring young scientists to join in the excitement of discovering why animals, especially the human animal, eat and drink. My interest in ingestive behavior started by chance in a freshman biology class at the University of Pennsylvania taught by Alan Epstein. Once I was exposed to the thrill of doing research my plans for medical school were abandoned and I traveled to the University of Cambridge in England where with James Fitzsimons I completed a Ph.D. in physiology on studies of thirst in rats. After I moved on to the University of Oxford, the early training in biologic mechanisms provided a good basis for studies in humans. We characterized the sensations associated with thirst and the mechanisms involved in its initiation and termination. We also continued to work with animal models in a series of studies of dietary obesity. The effect of dietary variety on rat's intake led to studies of sensory-specific satiety in humans. In recent years the primary interest of my lab has been how food properties affect intake, satiety, and body weight. At the Johns Hopkins School of Medicine and now at The Pennsylvania State University, we have conducted systematic studies of the effects of the macronutrients, variety, portion size, and energy density in both adults and children. Currently our research aims to understand how to leverage the robust effects of variety, portion size, and energy density to encourage healthy eating and drinking. Throughout my career I have been lucky to have been in supportive environments surrounded by creative, insightful, and diligent colleagues. PMID- 26861178 TI - Kleptoparasitism and aggressiveness are influenced by standard metabolic rate in eels. AB - Kleptoparasitism refers to either interspecific or intraspecific stealing of food already procured by other species or individuals. Within a given species, individuals might differ in their propensity to use such a tactic, in a similar manner to which they differ in their general level of aggressiveness. Standard metabolic rate is often viewed as a proxy for energy requirements. For this reason, it should directly impact on both kleptoparasitism and aggressiveness when individuals have to share the same food source. In the present study we first assessed the standard metabolic rate (SMR) of 128 juvenile European eels (Anguilla anguilla) by the determination of oxygen consumption. We then tested how the SMR could influence agonistic behavior of individuals competing for food in three distinct trials evenly distributed over three months. We demonstrate that SMR positively correlates with attacks (sum of bite and push events) in all trials. Similarly SMR correlated positively with kleptoparasitism (food theft), but this was significant only for the third trial (month 3). To our knowledge, the present study is the first reporting a link between kleptoparasitism and SMR in a fish species. This has ecological implications owing to the fact that this species is characterized by an environmental sex determination linked to early growth rate. We discuss theses findings in the light of the producer-scrounger foraging game. PMID- 26861177 TI - Antidepressant behavior in thyroidectomized Wistar rats is induced by hippocampal hypothyroidism. AB - Thyroidectomy is a surgical procedure indicated in cases of several maligned or benign thyroid diseases, thus, the aim of our study was to verify how the hypothyroidism induced by thyroidectomy influences behavioral parameters and its relation to thyroid hormones metabolism and neurogenesis at hippocampus. For this purpose, Adult male Wistar rats underwent to thyroidectomy to induce hypothyroidism. Behavioral tests, the thyroid profile and hippocampal gene expression were evaluated in control and in thyroidectomized animals. It was observed that thyroidectomized group had a significant increasing in serum thyroid-stimulating hormone (TSH) and a decreasing in thyroxine (T4) levels as well as in triiodothyronine (T3) serum level. It was also observed reduction of the monocarboxylate transporter 8 (Mct8), thyroid hormone receptor alfa (Tralpha1), deiodinase type 2 (Dio2), ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2) and brain-derived neurotrophic factor (Bdnf) mRNA expression in hippocampus of thyroidectomized animals. In the forced swimming test, it was verified that thyroidectomy promotes a decrease in time of immobility and climbing when compared with the control group. In summary, we demonstrated that antidepressant behavior in thyroidectomized Wistar rats is induced by hippocampal hypothyroidism. This effect could be associated to an impaired neuronal activity in acute stress response as it is observed in forced swimming paradigm. PMID- 26861179 TI - Functional roles of low calorie sweeteners on gut function. AB - This short review summarizes the effects of low calorie sweeteners (fructose, non nutritive low calorie sweeteners) on gut functions focusing on the gut sweet taste receptor system. The effects of these molecules on secretion of gut peptides associated with glycemic homeostasis and appetite regulation is reviewed as well as effects on gastric emptying and glucose absorption. PMID- 26861180 TI - Editorial. PMID- 26861182 TI - Spotlight on DNA repair and responses to DNA damage. PMID- 26861181 TI - A Personal Tribute to 2015 Nobel Laureate Paul Modrich. PMID- 26861183 TI - Mismatch repair earns Nobel Prize in Chemistry 2015 to Paul Modrich for a biochemical tour de force. PMID- 26861184 TI - Tomas Lindahl: 2015 Nobel Laureate. PMID- 26861186 TI - A history of the DNA repair and mutagenesis field: The discovery of base excision repair. AB - This article reviews the early history of the discovery of an DNA repair pathway designated as base excision repair (BER), since in contrast to the enzyme catalyzed removal of damaged bases from DNA as nucleotides [called nucleotide excision repair (NER)], BER involves the removal of damaged or inappropriate bases, such as the presence of uracil instead of thymine, from DNA as free bases. PMID- 26861187 TI - Vascular Function and Myocardial Performance Indices in Children Born Small for Gestational Age. AB - BACKGROUND: Small-for-gestational-age (SGA) children have increased cardiovascular risk, but the mediating factors are poorly understood. We hypothesized that birth size could affect the cardiovascular system since childhood in the absence of other risk factors. We investigated endothelial and myocardial function in SGA children with regular catch-up growth. METHODS AND RESULTS: Biochemical markers, blood pressure, flow-mediated vasodilation (FMD), common carotid intima-media thickness (cIMT), anteroposterior diameter of the infrarenal abdominal aorta (APAO) and echocardiographic parameters of left and right ventricular (LV and RV) function were studied in 27 SGA and 25 appropriate for-gestational-age (AGA) subjects. SGA subjects had a higher homeostasis model assessment index than controls (2.61+/-1.27 vs. 1.56+/-0.40, P=0.01), higher cIMT (0.51+/-0.04 mm vs. 0.45+/-0.07 mm, P=0.007) and APAO (1.31+/-1.35 cm vs. 1.30+/ 0.16 cm, P=0.005), and lower FMD (10.11+/-4.17% vs. 12.34+/-4.28, P=0.04) than controls. On echocardiography SGA had higher Tei index both at LV and RV than controls (P=0.001). Reduced RV systolic function was also observed in SGA subjects. CONCLUSIONS: SGA subjects had vascular morphological and function abnormalities compared with AGA, which increase their cardiovascular risk profile. Furthermore, a subtle cardiac alteration in both RV and LV functions was seen in SGA patients compared with AGA. PMID- 26861185 TI - A tale of two cities: A tribute to Aziz Sancar's Nobel Prize in Chemistry for his molecular characterization of NER. PMID- 26861189 TI - Exploring the topological sources of robustness against invasion in biological and technological networks. AB - For a network, the accomplishment of its functions despite perturbations is called robustness. Although this property has been extensively studied, in most cases, the network is modified by removing nodes. In our approach, it is no longer perturbed by site percolation, but evolves after site invasion. The process transforming resident/healthy nodes into invader/mutant/diseased nodes is described by the Moran model. We explore the sources of robustness (or its counterpart, the propensity to spread favourable innovations) of the US high voltage power grid network, the Internet2 academic network, and the C. elegans connectome. We compare them to three modular and non-modular benchmark networks, and samples of one thousand random networks with the same degree distribution. It is found that, contrary to what happens with networks of small order, fixation probability and robustness are poorly correlated with most of standard statistics, but they depend strongly on the degree distribution. While community detection techniques are able to detect the existence of a central core in Internet2, they are not effective in detecting hierarchical structures whose topological complexity arises from the repetition of a few rules. Box counting dimension and Rent's rule are applied to show a subtle trade-off between topological and wiring complexity. PMID- 26861188 TI - Naringenin targets ERK2 and suppresses UVB-induced photoaging. AB - A number of natural phytochemicals have anti-photoaging properties that appear to be mediated through the inhibition of matrix metalloproteinase-1 (MMP-1) expression, but their direct target molecule(s) and mechanism(s) remain unclear. We investigated the effect of naringenin, a major flavonoid found in citrus, on UVB-induced MMP-1 expression and identified its direct target. The HaCaT human skin keratinocyte cell line and 3-dimensional (3-D) human skin equivalent cultures were treated or not treated with naringenin for 1 hr before exposure to UVB. The mechanism and target(s) of naringenin were analysed by kinase assay and multiplex molecular assays. Dorsal skins of hairless mice were exposed to UVB 3 times per week, with a dose of irradiation that was increased weekly by 1 minimal erythema dose (MED; 45 mJ/cm(2)) to 4 MED over 15 weeks. Wrinkle formation, water loss and water content were then assessed. Naringenin suppressed UVB-induced MMP 1 expression and AP-1 activity, and strongly suppressed UVB-induced phosphorylation of Fos-related antigen (FRA)-1 at Ser265. Importantly, UVB irradiation-induced FRA1 protein stability was reduced by treatment with naringenin, as well as with a mitogen-activated protein kinase (MEK) inhibitor. Naringenin significantly suppressed UVB-induced extracellular signal-regulated kinase 2 (ERK2) activity and subsequently attenuated UVB-induced phosphorylation of p90(RSK) by competitively binding with ATP. Constitutively active MEK (CA-MEK) increased FRA1 phosphorylation and expression and also induced MMP-1 expression, whereas dominant-negative ERK2 (DN-ERK2) had opposite effects. U0126, a MEK inhibitor, also decreased FRA1 phosphorylation and expression as well as MMP-1 expression. The photoaging data obtained from mice clearly demonstrated that naringenin significantly inhibited UVB-induced wrinkle formation, trans-epidermal water loss and MMP-13 expression. Naringenin exerts potent anti-photoaging effects by suppressing ERK2 activity and decreasing FRA1 stability, followed by down-regulation of AP-1 transactivation and MMP-1 expression. PMID- 26861191 TI - Achromatic vector vortex beams from a glass cone. AB - The reflection of light is governed by the laws first described by Augustin-Jean Fresnel: on internal reflection, light acquires a phase shift, which depends on its polarization direction with respect to the plane of incidence. For a conical reflector, the cylindrical symmetry is echoed in an angular variation of this phase shift, allowing us to create light modes with phase and polarization singularities. Here we observe the phase and polarization profiles of light that is back reflected from a solid glass cone and, in the case of circular input light, discover that not only does the beam contain orbital angular momentum but can trivially be converted to a radially polarized beam. Importantly, the Fresnel coefficients are reasonably stable across the visible spectrum, which we demonstrate by measuring white light polarization profiles. This discovery provides a highly cost-effective technique for the generation of broadband orbital angular momentum and radially polarized beams. PMID- 26861190 TI - Differential Expression of Genes and DNA Methylation associated with Prenatal Protein Undernutrition by Albumen Removal in an avian model. AB - Previously, long-term effects on body weight and reproductive performance have been demonstrated in the chicken model of prenatal protein undernutrition by albumen removal. Introduction of such persistent alterations in phenotype suggests stable changes in gene expression. Therefore, a genome-wide screening of the hepatic transcriptome by RNA-Seq was performed in adult hens. The albumen deprived hens were created by partial removal of the albumen from eggs and replacement with saline early during embryonic development. Results were compared to sham-manipulated hens and non-manipulated hens. Grouping of the differentially expressed (DE) genes according to biological functions revealed the involvement of processes such as 'embryonic and organismal development' and 'reproductive system development and function'. Molecular pathways that were altered were 'amino acid metabolism', 'carbohydrate metabolism' and 'protein synthesis'. Three key central genes interacting with many DE genes were identified: UBC, NR3C1, and ELAVL1. The DNA methylation of 9 DE genes and 3 key central genes was examined by MeDIP-qPCR. The DNA methylation of a fragment (UBC_3) of the UBC gene was increased in the albumen-deprived hens compared to the non-manipulated hens. In conclusion, these results demonstrated that prenatal protein undernutrition by albumen removal leads to long-term alterations of the hepatic transcriptome in the chicken. PMID- 26861192 TI - Near-field engineering of Fano resonances in a plasmonic assembly for maximizing CARS enhancements. AB - Surface enhanced coherent anti-Stokes Raman scattering (SECARS) is a sensitive tool and promising for single molecular detection and chemical selective imaging. However, the enhancement factors (EF) were only 10~100 for colloidal silver and gold nanoparticles usually used as SECARS substrates. In this paper, we present a design of SECARS substrate consisting of three asymmetric gold disks and strategies for maximizing the EF by engineering near-field properties of the plasmonic Fano nanoassembly. It is found that the E-field "hot spots" corresponding to three different frequencies involved in SECARS process can be brought to the same spatial locations by tuning incident orientations, giving rise to highly confined SECARS "hot spots" with the EF reaching single-molecule sensitivity. Besides, an even higher EF of SECARS is achieved by introducing double Fano resonances in this plasmonic nanoassembly via further enlarging the sizes of the constituent disks. These findings put an important step forward to the plasmonic substrate design for SECARS as well as for other nonlinear optical processes. PMID- 26861193 TI - Fatal pulmonary Kaposi sarcoma in an HIV seronegative AIDS patient. AB - INTRODUCTION: Although HIV antibody tests have been widely accepted in clinical diagnosis of HIV infection, they may not be sufficient to diagnose all subjects with HIV infection. Except negative result of antibody test in the well-known" acute window phase", in rare cases, patients do not develop HIV antibodies despite demonstrable infection. Primary pulmonary Kaposi sarcoma (KS) without mucocutaneous involvement accounts for only 0-15% of all AIDS-related KS. KS is rare among Chinese subjects, especially in persons of Han descent. METHODS: A case of seronegative AIDS with primary pulmonary Kaposi sarcoma (KS) was reported. It's a 46-year-old Chinese man presented with sore throat, hemoptysis, fever, dyspnea and multiple lung nodules. The lung lesions grew over a 5-month period so as the symptoms worsened. The possibility of AIDS was discounted by his physicians because of the repeatedly negative HIV antibodies tests despite the ELISA tests or Western blot tests. Histopathologic diagnosis of fine needle lung biopsy in local hospital was undetermined. After admission, HIV infection was eventually confirmed by plasma HIV RNA testing. Histopathologic diagnosis of Lung Kaposi sarcoma was made through repeated fine needle aspiration biopsy as well as the review of former one. Multiple antibiotics and chemotherapy were administrated with no clinical effect due to advanced stage and the patient passed away soon after diagnosis. RESULTS: This is the first case of seronegative HIV-1 infection with presentation of primary pulmonary KS. CONCLUSION: This case underscores the importance of plasma RNA test in conjunction with HIV antibody test for some rare patients with HIV infection who present with severe immunodeficiency and opportunistic infections or malignancy. PMID- 26861194 TI - Diversity and antifungal susceptibility of Norwegian Candida glabrata clinical isolates. AB - BACKGROUND: Increasing numbers of immunocompromised patients have resulted in greater incidence of invasive fungal infections with high mortality. Candida albicans infections dominate, but during the last decade, Candida glabrata has become the second highest cause of candidemia in the United States and Northern Europe. Reliable and early diagnosis, together with appropriate choice of antifungal treatment, is needed to combat these challenging infections. OBJECTIVES: To confirm the identity of 183 Candida glabrata isolates from different human body sites using matrix-assisted laser desorption/ionization time of-flight (MALDI-TOF) and VITEK((r))2, and to analyze isolate protein profiles and antifungal susceptibility. The minimum inhibitory concentration (MIC) of seven antifungal drugs was determined for the isolates to elucidate susceptibility. DESIGN: A total of 183 C. glabrata isolates obtained between 2002 and 2012 from Norwegian health-care units were analyzed. For species verification and differentiation, biochemical characterization (VITEK((r))2) and mass spectrometry (MALDI-TOF) were used. MIC determination for seven antifungal drugs was undertaken using E-tests((r)). RESULTS: Using VITEK((r))2, 92.9% of isolates were identified as C. glabrata, while all isolates (100%) were identified as C. glabrata using MALDI-TOF. Variation in protein spectra occurred for all identified C. glabrata isolates. The majority of isolates had low MICs to amphotericin B (<=1 mg/L for 99.5%) and anidulafungin (<=0.06 mg/L for 98.9%). For fluconazole, 18% of isolates had MICs >32 mg/L and 82% had MICs in the range >=0.016 mg/L to <=32 mg/L. CONCLUSIONS: Protein profiles and antifungal susceptibility characteristics of the C. glabrata isolates were diverse. Clustering of protein profiles indicated that many azole resistant isolates were closely related. In most cases, isolates had highest susceptibility to amphotericin B and anidulafungin. The results confirmed previous observations of high MICs to fluconazole and flucytosine. MALDI-TOF was more definitive than VITEK((r))2 for C. glabrata identification. PMID- 26861195 TI - Hydrogen Peroxide Vapor Decontamination in a Patient Room Using Feline Calicivirus and Murine Norovirus as Surrogate Markers for Human Norovirus. AB - OBJECTIVE: To determine whether hydrogen peroxide vapor (HPV) could be used to decontaminate caliciviruses from surfaces in a patient room. DESIGN: Feline calicivirus (FCV) and murine norovirus (MNV) were used as surrogate viability markers to mimic the noncultivable human norovirus. Cell culture supernatants of FCV and MNV were dried in triplicate 35-mm wells of 6-well plastic plates. These plates were placed in various positions in a nonoccupied patient room that was subsequently exposed to HPV. Control plates were positioned in a similar room but were never exposed to HPV. METHODS: Virucidal activity was measured in cell culture by reduction in 50% tissue culture infective dose titer for FCV and by both 50% tissue culture infective dose titer and plaque reduction for MNV. RESULTS: Neither viable FCV nor viable MNV could be detected in the test room after HPV treatment. At least 3.65 log reduction for FCV and at least 3.67 log reduction for MNV were found by 50% tissue culture infective dose. With plaque assay, measurable reduction for MNV was at least 2.85 log units. CONCLUSIONS: The successful inactivation of both surrogate viruses indicates that HPV could be a useful tool for surface decontamination of a patient room contaminated by norovirus. Hence nosocomial spread to subsequent patients can be avoided. PMID- 26861196 TI - Neuropathic pain induced by spinal cord injury: Role of endothelin ETA and ETB receptors. AB - Spinal cord injury (SCI) is a devastating neurologic disorder that often inflicts neuropathic pain, which further impacts negatively on the patient's quality of life. Endothelin peptides, which exert their effects via endothelin A (ETAR) and endothelin B (ETBR) receptors, can contribute to sensory changes associated with inflammatory and neuropathic pain, but their role in nociception following SCI is unknown. At different time points after subjecting male Wistar rats to surgery for compression-induced T10 level SCI, the spinal cord levels of ETAR and ETBR were assessed by Western blot and immunohistochemistry, and the corresponding mRNAs by real-time PCR, alongside recordings of behavioural responses to mechanical stimulation of the hind paws with von Frey hairs. SCI was associated with development of hind paw mechanical allodynia from day 14 onwards, and up regulation of ETAR and ETBR mRNA in the spinal cord and dorsal root ganglia, and of ETAR protein in the spinal cord. SCI increased ETAR protein expression in spinal grey matter. Treatment on day 21 after surgery with the ETAR selective antagonist BQ-123 (40 and 90 pmol, intrathecally) or the dual ETAR/ETBR antagonist bosentan (30 and 100mg/kg, orally) transiently reduced SCI-induced mechanical allodynia, but the ETBR antagonist BQ-788 was ineffective. Altogether, these data show that SCI upregulates ETAR expression in the spinal cord, which appears to contribute to the hind paw mechanical allodynia associated with this condition. Therapies directed towards blockade of spinal ETAR may hold potential to limit SCI-induced neuropathic pain. PMID- 26861197 TI - Test-retest reliability of ERP components: A short-term replication of a visual Go/NoGo task in ADHD subjects. AB - Event-related potentials (ERPs) have been widely used to investigate brain functioning in children with Attention Deficit Hyperactivity Disorder (ADHD) in both research and diagnostic settings. To ensure the efficiency of ERP techniques in ADHD diagnosis and in longitudinal observational studies, the test-retest reliability of the affected population must be validated. Thus, the present article assesses the short-term test-retest reliability of certain early and late ERPs (i.e., P1, N1, N2, P2, P3), as well as independent components (ICs) decomposed from the above mentioned ERPs (IC P3 Go, IC P3 NoGo early, IC P3 NoGo late) relevant to ADHD, through the Intraclass Correlation Coefficient (ICC). More specifically, we employ a cued visual Go/NoGo paradigm for recording ERPs from 22 children with ADHD (mean age 12.2), twice within 30 min. Amplitudes and latencies are calculated by the 'peak amplitude' method and by a variation of the fractional area. Results for amplitudes lie mostly within the 'good' and 'excellent' range for both measurement methods, while ICC for latencies is more variable ranging from 'poor' to 'excellent' results. Crucially, the ICs, which are associated with distinct functionally independent processes of the executive attentional system have shown a comparable test-retest reliability with the raw ERPs. Our results are consistent with other reliability studies of neurotypical population in the literature, and as such, consist initial evidence that ERPs could be reliable neurophysiological markers for the ADHD population. PMID- 26861199 TI - The effect of deviance predictability on mismatch negativity in schizophrenia patients. AB - Mismatch negativity (MMN) is an electrophysiological index of prediction error processing and recently has been considered an endophenotype marker in schizophrenia. While the prediction error is a core concept in the MMN generation, predictability of deviance occurrence has rarely been assessed in MMN research and in schizophrenia patients. We investigated the MMN to 12% temporally predictable or unpredictable duration decrement deviant stimuli in two runs in 29 healthy controls and 31 schizophrenia patients. We analyzed MMN amplitudes and latencies and its associations with clinical symptoms at electrode Fz. With a stimulus onset asynchronicity of 500 ms in the regular predictable condition, a deviant occurred every 4s while it varied randomly in the unpredictable condition. In the random condition we found diminished MMN amplitudes in patients which normalized in the regular deviance condition, resulting in an analysis of variance main effect of predictability and a predictability x group interaction. Deviance predictability did not affect the MMN of control subjects and we found no relevant results with regard to MMN latencies. Our results indicate that MMN amplitudes in patients normalize to the level of the control subjects in the case of a temporally fixed regular deviant. In schizophrenia patients the detection of deviance is basically intact. However, the temporal uncertainty of deviance occurrence may be of substantial relevance to the highly replicated MMN deficit in schizophrenia patients. PMID- 26861198 TI - Effects of chronic constriction injury and spared nerve injury, two models of neuropathic pain, on the numbers of neurons and glia in the rostral ventromedial medulla. AB - In previous studies we have reported that spinal nerve ligation (SNL), a model of neuropathic pain, results in the loss of over 20% of neurons in the rostral portion of the ventromedial medulla (RVM) in rats, 10 days after SNL. The RVM is involved in pain modulation and we have proposed that loss of pain inhibition from the RVM, including loss of RVM serotonin neurons, contributes to the increased hypersensitivity observed after SNL. In the present study we examined whether RVM neuronal loss occurs in two other models of neuropathic pain, chronic constriction injury (CCI) and spared nerve injury (SNI). We found no evidence for neuronal loss 10 days after either nerve injury, a time when robust tactile hypersensitivity is present in both CCI and SNI. We conclude that loss of RVM neurons appears not to be required for expression of tactile hypersensitivity in these models of neuropathic pain. PMID- 26861200 TI - Highly specific changes in antioxidant levels and lipid peroxidation in Parkinson's disease and its progression: Disease and staging biomarkers and new drug targets. AB - There is evidence that immune-inflammatory, stress of reactive oxygen and nitrogen species (IO&NS) processes play a role in the neurodegenerative processes observed in Parkinson's disease (PD). The aim of the present study was to investigate peripheral IO&NS biomarkers in PD. We included 56 healthy individuals and 56 PD patients divided in two groups: early PD stage and late PD stage. Plasma lipid hydroperoxides (LOOH), malondialdehyde (MDA), nitric oxide metabolites (NOx), sulfhydryl (SH) groups, catalase (CAT) activity, superoxide dismutase (SOD) activity, paraoxonase (PON)1 activity, total radical trapping antioxidant parameter (TRAP) and C-reactive protein (CRP) were measured. PD is characterized by increased LOOH, MDA and SOD activity and lowered CAT activity. A combination of five O&NS biomarkers highly significantly predicts PD with a sensitivity of 94.5% and a specificity of 86.8% (i.e., MDA, SOD activity, TRAP, SH-groups and CAT activity). The single best biomarker of PD is MDA, while LOOH and SOD activity are significantly associated with late PD stage, but not early PD stage. Antiparkinson drugs did not affect O&NS biomarkers, but levodopa+carbidopa significantly increased CRP. It is suggested that MDA may serve as a disease biomarker, while LOOH and SOD activity are associated with late PD stage characteristic. New treatments for PD should not only target dopamine but also lipid peroxidation. PMID- 26861201 TI - Effects of Deltamethrin on crayfish motor axon activity and neuromuscular transmission. AB - Deltamethrin (DM) is a widely used pesticide known to target sodium channels. Although this compound has been studied extensively at molecular and behavioral levels, the detailed action of DM on cellular and synaptic function is less well documented. In this report, we show that DM at nanomolar concentrations can silence tonic motor output of the crayfish ventral superficial flexor (VSF) within ~10 min. Action potential (AP) amplitude was consistently reduced before silencing occurred, whereas AP duration and AP firing frequency did not change. In some synapses EPSP amplitude and synaptic delay were modified by DM, but the direction of change was not consistent. In order to better understand these diverse effects, intracellular recordings from motor axons of the crayfish opener were used for a detailed analysis. DM caused an initial, slow depolarization of resting membrane potential (Vm), which was accompanied by reduced AP amplitude but not AP duration. Resting Vm then underwent a step depolarization of ~20 mV, which we propose corresponds to the onset of the depolarization block. In addition, DM shifted the AP initiation site in some opener axons during prolonged firing. This shift occurred concomitantly with a reduction in synaptic delay. A similar reduction in synaptic delay was also detected at some VSF axons, and can be attributed to the same mechanism. Results reported here suggest that DM at low concentrations result in: (i) depolarization block of motor axons before changes in network output can be detected, (ii) variable effects on synaptic transmission, with this variability presumably due to the diverse morphology and excitability of motor axons. PMID- 26861202 TI - MRI T2* imaging for assessment of liver iron overload: study of different data analysis approaches. AB - Background Recently, magnetic resonance imaging (MRI) has been established as an effective technique for evaluating iron overload by measuring T2* in the liver. Purpose To investigate the effects of various factors associated with T2* calculation on the resulting measurement and to determine the analysis criterion that provides the most accurate T2* measurements. Material and Methods Both phantom and in vivo MRI experiments were conducted to study the effects of the selected region of interest (ROI) location and size, signal-averaging method, exponential-fitting model, echo truncation, iron-overload severity, and inter /intra-observer variabilities on T2* measurements. The results were compared to reference values from the scanner processing software. Results The pixel-by-pixel calculation method provided results in better agreement with the reference values from the MRI scanner than the average or median methods. The choice of the exponential fitting model affected the results, depending on signal-to-noise ratio, number of echoes, minimum and maximum echo times, and tissue composition inside the selected ROI. The single-exponential model resulted in smaller error than the bi-exponential or exponential-plus-constant models, where the latter two models showed similar results. The relative performance of the different models and methods was not affected by the degree of iron-overload. Conclusion Various factors associated with the adopted T2* calculation method affect the resulting measurement. In this study, the pixel-by-pixel calculation method and single exponential model provided the most accurate results based on the conducted phantom and in vivo MRI experiments. PMID- 26861203 TI - MRI of the left atrium at 3T: evaluation of measurement reproducibility in healthy volunteers and patients with cardiovascular disease. AB - Background Left ventricular (LV) function has traditionally been the focus for cardiac magnetic resonance imaging (MRI) investigations, but similar methods can also be applied to the left atrium (LA). Previous studies elsewhere have almost entirely involved the use of 1.5T systems, but 3T MRI can provide faster data acquisition with thinner image slices, and may be more suitable for quantifying the structure and function of the LA. Purpose To evaluate 3T-MRI for LA volume assessments in: (i) healthy volunteers (HV); (ii) patients with LV-hypertrophy and ischemia (LVHI); and (iii) patients with LV-hypertrophy and diabetes (LVHD). Material and Methods Participants were imaged using a balanced steady-state free precession sequence. Healthy volunteers were scanned twice and patients were scanned on one occasion. Volumes were segmented by two observers, and coefficients of repeatability (CoR) were derived. Results For LA volumes (indexed to body surface area), CoRs were in the range of 1.3-4.6 mL/m2. The LVHI patients had enlarged LA volumes (diastolic, 46.4 mL/m2; systolic, 25.9 mL/m2) and reduced ejection fraction (EF) (44.9%) relative to the HV (diastolic, 39.0 mL/m2; systolic, 17.8 mL/m2; EF, 54.5%) and LVHD groups (diastolic, 41.4 mL/m2; systolic, 20.2 mL/m2; EF, 50.7%). LA volumes were moderately correlated with LV mass in the HV group (R2 = 0.59 for LA end-systolic volume), but became weaker (R2 <= 0.17) for patient groups. Conclusion 3T-MRI derived LA volume measurements are simple and repeatable, and can elicit clear differences between LVHI patients and HVs. These MRI endpoints provide scope for improved radiological interpretation of LA structure and function, and the high degree of repeatability validates their use for longitudinal investigations where precision work is essential. PMID- 26861204 TI - Which system is better to predict prognosis of patients with hepatocellular carcinoma treated by transcatheter arterial chemoembolization as initial therapy? Comparison between CLIP and JIS in a Japanese population. AB - Background There has been no consensus as to which system, either the Cancer of the Liver Italian Program (CLIP) or the Japan Integrated Staging (JIS) system, is suitable to predict the prognosis of hepatocellular carcinoma (HCC) patients who underwent transcatheter arterial chemoembolization (TACE) as initial therapy. Purpose To retrospectively compare the usefulness of CLIP and JIS in predicting and stratifying the prognosis of HCC patients treated by TACE. Material and Methods Between 1995 and 2005, consecutive 728 patients with untreated HCC who underwent TACE in our institute were selected for this study. The survival rate and its prognostic factors were assessed by multivariate analysis. Patients were stratified according to the two systems, and their survival rates between the scores were compared. Results The mean follow-up period was 1689 days. The 1 year, 3-year, 5-year, and 10-year survival rates were 83.1%, 55.1%, 34.7%, and 12.8%, respectively. Both systems stratified the prognosis of patients well, but was slightly better in CLIP as compared to in JIS. As for multivariate factor analysis, less severe Child-Pugh classification ( P < 0.001), simple tumor morphology ( P < 0.001), absence of portal vein invasion ( P < 0.001), and lower alpha-fetoprotein (AFP) level ( P < 0.001) were suggested to be independent indicators for favorable survival rate. All of these independent factors were included in CLIP, whereas JIS lacked AFP level. Furthermore, the likelihood chi2 test value was higher, and the Akaike information criterion value was lower for CLIP than for JIS. Conclusion CLIP is more suitable than JIS for predicting prognosis of patients with HCC who would undergo TACE in a Japanese population. PMID- 26861205 TI - Optimal detection of scapholunate ligament tears with MRI. AB - Background Scapholunate interosseous ligament (SLIL) injuries can often be difficult to detect using magnetic resonance imaging (MRI), especially with older 1.0 and 1.5 Tesla magnets. Wrist arthroscopy is the gold standard for diagnosis of SLIL injuries, but is an invasive procedure with associated risks. Purpose To assess whether SLIL injuries can be more accurately detected using axial MRI sequences instead of coronal sequences. Material and Methods An institutional review board approved retrospective analysis of arthroscopic wrist surgeries performed at our institution. Patients that had a preoperative MRI performed at our university center using a 1.5 Tesla scanner with a dedicated wrist coil were included in the study. Three fellowship-trained musculoskeletal radiologists reviewed the axial sequences and coronal sequences independently. The accuracy of the coronal and axial sequences was compared with the arthroscopic/surgical findings. Result Twenty-six patients met the inclusion criteria. The sensitivity for SLIL tears was 79% and 65% for the axial and coronal sequences, respectively. The specificity was 82% for the axial and 69% for the coronal sequences, respectively. The positive and negative predictive values for the axial sequences were 76% and 84% respectively, compared to 68% and 71% for the coronal sequences, a statistically significant difference. Conclusion SLIL tears are more readily detectable on axial MRI sequences than coronal. Clinically, patients with radial sided wrist pain and suspicion for SLIL tears should have the axial sequences scrutinized carefully. An otherwise normal study with the axial sequence being degraded by motion or other MRI artifacts might need repeat imaging. PMID- 26861206 TI - Measuring the potential of individual airports for pandemic spread over the world airline network. AB - BACKGROUND: Massive growth in human mobility has dramatically increased the risk and rate of pandemic spread. Macro-level descriptors of the topology of the World Airline Network (WAN) explains middle and late stage dynamics of pandemic spread mediated by this network, but necessarily regard early stage variation as stochastic. We propose that much of this early stage variation can be explained by appropriately characterizing the local network topology surrounding an outbreak's debut location. METHODS: Based on a model of the WAN derived from public data, we measure for each airport the expected force of infection (AEF) which a pandemic originating at that airport would generate, assuming an epidemic process which transmits from airport to airport via scheduled commercial flights. We observe, for a subset of world airports, the minimum transmission rate at which a disease becomes pandemically competent at each airport. We also observe, for a larger subset, the time until a pandemically competent outbreak achieves pandemic status given its debut location. Observations are generated using a highly sophisticated metapopulation reaction-diffusion simulator under a disease model known to well replicate the 2009 influenza pandemic. The robustness of the AEF measure to model misspecification is examined by degrading the underlying model WAN. RESULTS: AEF powerfully explains pandemic risk, showing correlation of 0.90 to the transmission level needed to give a disease pandemic competence, and correlation of 0.85 to the delay until an outbreak becomes a pandemic. The AEF is robust to model misspecification. For 97 % of airports, removing 15 % of airports from the model changes their AEF metric by less than 1 %. CONCLUSIONS: Appropriately summarizing the size, shape, and diversity of an airport's local neighborhood in the WAN accurately explains much of the macro-level stochasticity in pandemic outcomes. PMID- 26861207 TI - Feedback activation of neurofibromin terminates growth factor-induced Ras activation. AB - BACKGROUND: Growth factors induce a characteristically short-lived Ras activation in cells emerging from quiescence. Extensive work has shown that transient as opposed to sustained Ras activation is critical for the induction of mitogenic programs. Mitogen-induced accumulation of active Ras-GTP results from increased nucleotide exchange driven by the nucleotide exchange factor Sos. In contrast, the mechanism accounting for signal termination and prompt restoration of basal Ras-GTP levels is unclear, but has been inferred to involve feedback inhibition of Sos. Remarkably, how GTP-hydrolase activating proteins (GAPs) participate in controlling the rise and fall of Ras-GTP levels is unknown. RESULTS: Monitoring nucleotide exchange of Ras in permeabilized cells we find, unexpectedly, that the decline of growth factor-induced Ras-GTP levels proceeds in the presence of unabated high nucleotide exchange, pointing to GAP activation as a major mechanism of signal termination. Experiments with non-hydrolysable GTP analogues and mathematical modeling confirmed and rationalized the presence of high GAP activity as Ras-GTP levels decline in a background of high nucleotide exchange. Using pharmacological and genetic approaches we document a raised activity of the neurofibromatosis type I tumor suppressor Ras-GAP neurofibromin and an involvement of Rsk1 and Rsk2 in the down-regulation of Ras-GTP levels. CONCLUSIONS: Our findings show that, in addition to feedback inhibition of Sos, feedback stimulation of the RasGAP neurofibromin enforces termination of the Ras signal in the context of growth-factor signaling. These findings ascribe a precise role to neurofibromin in growth factor-dependent control of Ras activity and illustrate how, by engaging Ras-GAP activity, mitogen-challenged cells play safe to ensure a timely termination of the Ras signal irrespectively of the reigning rate of nucleotide exchange. PMID- 26861209 TI - Euryphorus brachypterus (Copepoda: Caligidae) on wild pacific bluefin tuna from the Tsugaru Strait, northern Japan. AB - Parasitic copepods infecting large scombrid fishes have been known for a long time because their hosts are economically important. Most studies, however, have focused on their morphology or their infection status in aquaculture from pathological viewpoints, and very few quantitative surveys have been conducted under conditions in the wild. This study therefore investigated the prevalence of Euryphorus brachypterus (Caligidae) in wild Pacific bluefin tuna (PBF). Results of sampling from August to September 2014 at the western area of the Tsugaru Strait, Japan showed that 13.2% of the PBF individuals (n = 1978) were infected with this copepod. The prevalence of infections was highest in larger fish but varied among landing dates, which were classified into three clusters and in all smaller fish, the prevalence of infections was zero. This suggests that E. brachypterus mainly uses the larger PBF, which becomes sources of further infections in other seas, and that at least two host populations with different infection statuses at the strait. PMID- 26861208 TI - Use of imaging and clinical data to screen for cardiovascular disease in asymptomatic diabetics. AB - BACKGROUND: There is increasing evidence to suggest that not all individuals with type 2 diabetes mellitus (T2DM) have equal risk for developing cardiovascular disease. We sought to compare the yield of testing for pre-clinical atherosclerosis with various approaches. METHODS: 98 asymptomatic individuals with T2DM without known coronary artery disease (CAD) were enrolled in a prospective study and underwent carotid ultrasound, exercise treadmill testing (ETT), coronary artery calcium (CAC) scoring, and coronary computed tomography angiography (CTA). RESULTS: Of 98 subjects (average age 55 +/- 6, 64 % female), 43 (44 %) had coronary plaque detectable on CTA, and 38 (39 %) had CAC score >0. By CTA, 16 (16 %) had coronary stenosis >=50 %, including three subjects with CAC = 0. Subjects with coronary plaque had greater prevalence of carotid plaque (58 % vs. 38 %, p = 0.01) and greater carotid intima media thickness (0.80 +/- 0.20 mm vs. 0.70 +/- 0.11 mm, p = 0.02). Notably, 18 of 55 subjects (33 %) with normal CTA had carotid plaque. Eight subjects had a positive ETT, of whom five had >= 50 % coronary stenosis, two had <50 % stenosis, and one had no CAD. Among these tests, CAC scoring had the highest sensitivity and specificity for prediction of CAD. CONCLUSION: Among asymptomatic subjects with T2DM, a majority (56 %) had no CAD by CTA. When compared to CTA, CAC was the most accurate screening modality for detection of CAD, while ETT and carotid ultrasound were less sensitive and specific. However, 33 % of subjects with normal coronary CTA had carotid plaque, suggesting that screening for carotid plaque might better characterize stroke risk in such patients. PMID- 26861210 TI - Dissociating proactive and reactive control in the Stroop task. AB - The Dual Mechanisms of Control framework posits the existence of two distinct control mechanisms, proactive and reactive, which may operate independently. However, this independence has been difficult to study with most experimental paradigms. The Stroop task may provide a useful way of assessing the independence of control mechanisms because the task elicits two types of proportion congruency effects, list-wide and item-specific, thought to reflect proactive and reactive control respectively. The present research tested whether these two proportion congruency effects can be used to dissociate proactive and reactive control. In 2 separate participant samples, we demonstrate that list-wide and item-specific proportion congruency effects are stable, exist in the same participants, and appear in different task conditions. Moreover, we identify two distinct behavioral signatures, the congruency cost and the transfer cost, which doubly dissociate the two effects. Together, the results are consistent with the view that proactive and reactive control reflect independent mechanisms. PMID- 26861212 TI - Extending migrant charging into emergency services. PMID- 26861211 TI - Absolute cardiovascular risk in a Fiji medical zone. AB - BACKGROUND: The population of Fiji has experienced emergence of non-communicable disease (NCD) and a plateau in life expectancy over the past 20 years. METHODS: A mini-STEPS survey (n = 2765) was conducted in Viseisei in Western Fiji to assess NCD risk factors (RFs) in i-Taukei (Melanesians) and those of Indian descent aged 25-64 years (response 73 %). Hypertension (HT) was defined as systolic blood pressure (BP) >=140 mmHg or diastolic BP >=90 mmHg or on medication for HT; type 2 diabetes mellitus (T2DM) as fasting plasma glucose >=7.0 mmol/L or on medication for T2DM; and obesity as a body mass index (kilograms/height(metres)(2)) >=30. Data were age-adjusted to 2007 Fiji Census. Associations between RFs and ethnicity/education were investigated. Comparisons with Fiji STEPS surveys were undertaken, and the absolute risk of a cardiovascular disease (CVD) event/death in 10 years was estimated from multiple RF charts. RESULTS: NCD/RFs increased with age except excessive alcohol intake and daily smoking (women) which declined. Daily smoking was higher in men 33 % (95 % confidence interval: 31-36) than women 14 % (12-116); women were more obese 40 % (37-43) than men 23 % (20-26); HT was similar in men 37 % (34-40) and women 34 % (31-36), as was T2DM in men 15 % (13-17) and women 17 % (15-19). i-Taukei men had an odds ratio (OR) of 0.41 (0.28-0.58) for T2DM compared to Indians (1.00); and i-Taukei (both sexes) had a higher OR for obesity and low fruit/vegetable intake, daily smoking, excessive alcohol intake and HT in females. Increasing education correlated with lesser smoking, but with higher obesity and lower fruit/vegetable intake. Compared to the 2011 Fiji STEPS survey, no significant differences were evident in obesity, HT or T2DM prevalences. The proportion (40-64 years) classified at high or very high risk (>=20 %) of a CVD event/death (over 10 years) based on multiple RFs was 8.3 % for men (8.1 % i Taukei, 8.5 % Indian), and 6.7 % for women (7.9 % i-Taukei, 6.0 % Indian). CONCLUSIONS: The results of the survey highlight the need for individual and community interventions to address the high levels of NCD/RFs. Evaluation of interventions is needed in order to inform NCD control policies in Fiji and other Pacific Island nations. PMID- 26861213 TI - Changes in cognitive function and brain glucose metabolism in elderly women with subjective memory impairment: a 24-month prospective pilot study. AB - OBJECTIVES: Subjective memory impairment (SMI) may precede mild cognitive impairment (MCI) stage and would offer an earlier therapeutic opportunity than MCI would. However, it is not clear whether complaints of forgetfulness are truly reflective of objective memory dysfunction or of impairments in other cognitive domains. The aim of this current longitudinal study was to investigate changes in various cognitive functions and in regional cerebral metabolic rate of glucose (rCMRglc) among elderly women with SMI. MATERIALS AND METHODS: Clinical evaluation, comprehensive neuropsychological test, and 18 F-fluoro-2-deoxyglucose positron emission tomography scans were conducted on 24 women with SMI at the baseline and 24-month follow-up. Changes in the cognitive domain scores and rCMRglc were assessed, and the relationships between them were analyzed. RESULTS: All participants stayed in SMI all the way till the follow-up, not converted to MCI or dementia. A significant reduction in executive function was found (mean difference in z-score: -0.21, P = 0.02) without changes in other cognitive domains. Declines in rCMRglc were detected in the left superior temporal gyrus, right posterior cingulate gyrus, left parahippocampal gyrus, right lingual gyrus, and right angular gyrus. The change in executive function had a positive correlation with the percent change of rCMRglc in the right posterior cingulate gyrus (beta = 0.43, P = 0.02). CONCLUSIONS: Our findings suggest that elderly women with SMI symptoms should be carefully monitored for declines in executive function and related brain glucose metabolism over time. PMID- 26861214 TI - Occupational eye lens doses in interventional cardiology. A multicentric study. AB - New European regulation regarding radiological protection of workers and more specifically the new occupational dose limit for the eye lens recently reduced to 20 mSv yr(-1) may affect interventional cardiologists. This paper presents a set of measurements of occupational doses performed in five interventional cardiology centres and then compared with the new dose limit. The measurement of occupational doses was performed over the apron at chest level using electronic dosemeters recording H p(10). In one of the centres, scatter dose at goggles was also measured with optically stimulated luminescence dosemeters calibrated in terms of H p(0.07). An average H p(10) over the apron of 46 MUSv/procedure was measured for cardiologists. Lower doses were noted in other professionals like second cardiologists, nurses or anaesthetists. Procedures for valvular and other structural heart diseases involved the highest occupational doses, averaging over 100 MUSv/procedure. Important differences in occupational doses among centres may be indicative of different radiation protection habits. The new occupational dose limit for the eye lens is likely to be exceeded by those among the interventionalists who do not use protection tools (ceiling suspended screen and/or goggles) even with standard workloads. PMID- 26861215 TI - Gleaning Structure from Sound: The Role of Prosodic Contrast in Learning Non adjacent Dependencies. AB - The ability to detect non-adjacent dependencies (i.e. between a and b in aXb) in spoken input may support the acquisition of morpho-syntactic dependencies (e.g. The princess is kiss ing the frog). Functional morphemes in morpho-syntactic dependencies are often marked by perceptual cues that render them distinct from lexical elements. We use an artificial grammar learning experiment with adults to investigate the role of perceptual cues in non-adjacent dependency learning, by manipulating the perceptual/prosodic properties of the a / b elements in aXb strings and testing participants' incidental learning of these dependencies. Our results show that non-adjacent dependencies are learned both when the dependent elements are perceptually prominent, and when they are perceptually reduced compared to the intervening material (in the same way that functional words are reduced compared to lexical words), but only if integrated into a natural prosodic contour. This result supports the idea that the prosodic properties of natural languages facilitate non-adjacent dependency learning. PMID- 26861216 TI - Single-Word Recognition Need Not Depend on Single-Word Features: Narrative Coherence Counteracts Effects of Single-Word Features that Lexical Decision Emphasizes. AB - Research on reading comprehension of connected text emphasizes reliance on single word features that organize a stable, mental lexicon of words and that speed or slow the recognition of each new word. However, the time needed to recognize a word might not actually be as fixed as previous research indicates, and the stability of the mental lexicon may change with task demands. The present study explores the effects of narrative coherence in self-paced story reading to single word feature effects in lexical decision. We presented single strings of letters to 24 participants, in both lexical decision and self-paced story reading. Both tasks included the same words composing a set of adjective-noun pairs. Reading times revealed that the tasks, and the order of the presentation of the tasks, changed and/or eliminated familiar effects of single-word features. Specifically, experiencing the lexical-decision task first gradually emphasized the role of single-word features, and experiencing the self-paced story-reading task afterwards counteracted the effect of single-word features. We discuss the implications that task-dependence and narrative coherence might have for the organization of the mental lexicon. Future work will need to consider what architectures suit the apparent flexibility with which task can accentuate or diminish effects of single-word features. PMID- 26861217 TI - Results of pediatric living donor compared to deceased donor liver transplantation in the PELD/MELD era: Experience from two centers on two different continents. AB - The LDLT option in the pediatric population allows recipients to be transplanted early. A total of 202 consecutive pediatric liver transplants from two different institutions--108 (LDLT) and 94 (DDLT)--were retrospectively compared. Overall, one- and three-yr patient and graft survival were similar between DDLT and LDLT. ACR was greater in recipients of DDLT at one and three yr (50.8% and 61.0%) compared to LDLT (30.8% and 32.2%) (p = 0.002). When the data were stratified according to PELD/MELD score, LDLT with a low score had better one- and three-yr graft survival (96.2% and 96.2%) compared to DDLT (88.2% and 85.2%) (p = 0.02), with comparable patient survival (p = 0.75). Patient and graft survival were similar between DDLT and LDLT in the high PELD/MELD group. Lower incidence of ACR in both low and high PELD/MELD groups was (29.6% and 34.3%) for LDLT compared to DDLT (50.3% and 53.3%, p = 0.002 and p = 0.028, respectively). Regardless of PELD/MELD score, status, age group, and recipient weight, LDLT provides excellent patient and graft survival with a lower incidence of rejection compared to DDLT. PMID- 26861218 TI - A Japanese pedigree with a p.A95V mutation in the MYH9 gene demonstrates inherited macrothrombocytopenia without Alport manifestations. PMID- 26861219 TI - Are more effective placebos complicating clinical trials? PMID- 26861220 TI - Chemical shift assignments of the C-terminal EF-hand domain of alpha-actinin-1. AB - The regulation and localization of the neuronal voltage gated Ca(2+) channel CaV1.2 is important for synaptic plasticity associated with learning and memory. The cytoskeletal protein, alpha-actinin-1 is known to interact with CaV1.2 and stabilize its localization at the postsynaptic membrane. Here we report both backbone and sidechain NMR assignments for the C-terminal EF-hands (EF3 and EF4) of alpha-actinin-1 (residues 824-892, called ACTN_EF34) bound to the IQ-motif (residues 1644-1665) from CaV1.2 (BMRB accession no. 25902). PMID- 26861222 TI - Effect of feed starvation on side-stream anammox activity and key microbial populations. AB - The anaerobic ammonium oxidation (anammox) process is widely acknowledged to be susceptible to a wide range of environmental factors given the slow growth rate of the anammox bacteria. Surprisingly there is limited experimental data regarding the susceptibility of the anammox process to feed starvations which may be encountered in full-scale applications. Therefore, a study was established to investigate the impact of feed starvations on nitritation and anammox activity in a demonstration-scale sequencing batch reactor. Three starvation periods were trialled, lasting one fortnight (15 d), one month (33 d) and two months (62 d). Regardless of the duration of the starvation period, assessment of the ammonia removal performance demonstrated nitritation and anammox activity were reinstated within one day of recovery operation. Characterisation of the community structure using 16S rRNA and functional genes specific for nitrogen-related microbes showed there was no clear impact or shift in the microbial populations between starvation and recovery phases. PMID- 26861221 TI - A Novel BLyS Peptibody Down-Regulates B Cell and T Helper Cell Subsets In Vivo and Ameliorates Collagen-Induced Arthritis. AB - B lymphocyte stimulator (BLyS), a member of tumor necrosis factor (TNF) family, contributes to the development of autoimmune disease, and BLyS antagonists have been developed for the treatment of autoimmune disorders. Recently, we constructed a novel BLyS antagonist, TC-Fc peptibody. The study was performed to investigate the efficiency of TC-Fc peptibody on collagen-induced arthritis (CIA). CIA mice were randomly divided into three groups, treated with TC-Fc, Fc, and phosphate-buffered saline (PBS), respectively. Clinical scores associated with the severity of arthritis were assessed on alternate day from first day. Histopathological scores, B and T cell changes, and autoantibodies levels were measured at the end of the experiment. CIA mice treated with TC-Fc peptibody had lower clinical and histological scores. Compared with Fc group, TC-Fc treatment resulted in reduction of B cell and T help cell subsets, significantly alleviated the swelling of paws, and suppressed articular tissue degeneration. These results demonstrated that TC-Fc could inhibit the progression of CIA and might have therapeutic effect on rheumatoid arthritis. PMID- 26861223 TI - Information preferences for the evaluation of coastal development impacts on ecosystem services: A multi-criteria assessment in the Australian context. AB - Ecosystem based management requires the integration of various types of assessment indicators. Understanding stakeholders' information preferences is important, in selecting those indicators that best support management and policy. Both the preferences of decision-makers and the general public may matter, in democratic participatory management institutions. This paper presents a multi criteria analysis aimed at quantifying the relative importance to these groups of economic, ecological and socio-economic indicators usually considered when managing ecosystem services in a coastal development context. The Analytic Hierarchy Process (AHP) is applied within two nationwide surveys in Australia, and preferences of both the general public and decision-makers for these indicators are elicited and compared. Results show that, on average across both groups, the priority in assessing a generic coastal development project is for the ecological assessment of its impacts on marine biodiversity. Ecological assessment indicators are globally preferred to both economic and socio-economic indicators regardless of the nature of the impacts studied. These results are observed for a significantly larger proportion of decision-maker than general public respondents, questioning the extent to which the general public's preferences are well reflected in decision-making processes. PMID- 26861224 TI - Performance of wind-powered soil electroremediation process for the removal of 2,4-D from soil. AB - In this work, it is studied a wind-powered electrokinetic soil flushing process for the removal of pesticides from soil. This approach aims to develop an eco friendly electrochemical soil treatment technique and to face the in-situ treatment of polluted soils at remote locations. Herbicide 2,4 dichlorophenoxyacetic acid (2,4-D) is selected as a model pollutant for the soil treatment tests. The performance of the wind-powered process throughout a 15 days experiment is compared to the same remediation process powered by a conventional DC power supply. The wind-powered test covered many different wind conditions (from calm to near gale), being performed 20.7% under calm conditions and 17% under moderate or gentle breeze. According to the results obtained, the wind powered soil treatment is feasible, obtaining a 53.9% removal of 2,4-D after 15 days treatment. Nevertheless, the remediation is more efficient if it is fed by a constant electric input (conventional DC power supply), reaching a 90.2% removal of 2,4-D with a much lower amount of charge supplied (49.2 A h kg(-1) and 4.33 A h kg(-1) for wind-powered and conventional) within the same operation time. PMID- 26861225 TI - Evaluating the impacts of landscape positions and nitrogen fertilizer rates on dissolved organic carbon on switchgrass land seeded on marginally yielding cropland. AB - Dissolved organic carbon (DOC) through leaching into the soils is another mechanism of net C loss. It plays an important role in impacting the environment and impacted by soil and crop management practices. However, little is known about the impacts of landscape positions and nitrogen (N) fertilizer rates on DOC leaching in switchgrass (Panicum virgatum L.). This experimental design included three N fertilizer rates [0 (low); 56 (medium); 112 (high) kg N ha(-1)] and three landscape positions (shoulder, backslope and footslope). Daily average DOC contents at backslope were significantly lower than that at shoulder and footslope. The DOC contents from the plots that received medium N rate were also significantly lower than the plots that received low N rates. The interactions of landscape and N rates on DOC contents were different in every year from 2009 to 2014, however, no significant consistent trend of DOC contents was observed over time. Annual average DOC contents from the plots managed with low N rate were higher than those with high N rate. These contents at the footslope were higher than that at the shoulder position. Data show that there is a moderate positive relationship between the total average DOC contents and the total average switchgrass biomass yields. Overall, the DOC contents from leachate in the switchgrass land were significantly influenced by landscape positions and N rates. The N fertilization reduced DOC leaching contents in switchgrass field. The switchgrass could retain soil and environment sustainability to some extent. These findings will assist in understanding the mechanism of changes in DOC contents with various parameters in the natural environment and crop management systems. However, use of long-term data might help to better assess the effects of above factors on DOC leaching contents and loss in the switchgrass field in the future. PMID- 26861226 TI - Carbon and water footprint of pork supply chain in Catalonia: From feed to final products. AB - A systematic tool to assess the Carbon Footprint (CF) and Water Footprint (WF) of pork production companies was developed and applied to representative Catalan companies. To do so, a cradle-to-gate environmental assessment was carried out by means of the LCA methodology, taking into account all the stages involved in the pork chain, from feed production to the processing of final products, ready for distribution. In this approach, the environmental results are reported based on eight different functional units (FUs) according to the main pork products obtained. With the aim of ensuring the reliability of the results and facilitating the comparison with other available reports, the Product Category Rules (PCR) for Catalan pork sector were also defined as a basis for calculations. The characterization results show fodder production as the main contributor to the global environmental burdens, with contributions higher than 76% regardless the environmental indicator or the life cycle stage considered, which is in agreement with other published data. In contrast, the results in terms of CF and WF lay above the range of values reported elsewhere. However, major discrepancies are mainly due to the differences in the co-products allocation criteria. In this sense, economic/physical allocation and/or system expansion have been mostly considered in literature. In contrast, no allocation was considered appropriate in this study, according to the characteristics of the industries and products under assessment; thus, the major impacts fall on the main product, which derives on comparatively higher environmental burdens. Finally, due to the relevance of fodder production in the overall impact assessment results, strategies to reduce greenhouse gases (GHG) emissions as well as water use associated to this stage were proposed in the pork supply chain. PMID- 26861227 TI - Readability and Understandability of Online Vocal Cord Paralysis Materials. AB - OBJECTIVE: Patients use several online resources to learn about vocal cord paralysis (VCP). The objective of this study was to assess the readability and understandability of online VCP patient education materials (PEMs), with readability assessments and the Patient Education Materials Evaluation Tool (PEMAT), respectively. The relationship between readability and understandability was then analyzed. STUDY DESIGN AND SETTING: Descriptive and correlational design. METHOD: Online PEMs were identified by performing a Google search with the term "vocal cord paralysis." After scientific webpages, news articles, and information for medical professionals were excluded, 29 articles from the first 50 search results were considered. Readability analysis was performed with 6 formulas. Four individuals with different educational backgrounds conducted understandability analysis with the PEMAT. Fleiss's Kappa interrater reliability analysis determined consistency among raters. Correlation between readability and understandability was determined with Pearson's correlation test. RESULTS: The reading level of the reviewed articles ranged from grades 9 to 17. Understandability ranged from 29% to 82%. Correlation analysis demonstrated a strong negative correlation between materials' readability and understandability (r = -0.462, P < .05). CONCLUSION: Online PEMs pertaining to VCP are written above the recommended reading levels. Overall, materials written at lower grade levels are more understandable. However, articles of identical grade levels had varying levels of understandability. The PEMAT may provide a more critical evaluation of the quality of a PEM when compared with readability formulas. Both readability and understandability should be used to evaluate PEMs. PMID- 26861228 TI - Effect of Radiofrequency Thermal Ablation Treatment on Nasal Ciliary Motility: A Study with Phase-Contrast Microscopy. AB - OBJECTIVE: To investigate the efficacy of nasal ciliary motility after radiofrequency ablation treatment in patients with isolated inferior turbinate hypertrophy and to clarify how long until normal ciliary function is restored. STUDY DESIGN: Prospective, single-group, pretest-posttest design. SETTING: Academic tertiary care medical center. SUBJECTS AND METHODS: This study involved 34 adult patients affected by nasal obstruction due to inferior turbinate hypertrophy who underwent radiofrequency ablation treatment between June and December 2014. Diagnosis was assessed according to clinical history, nasal endoscopy, and active anterior rhinomanometry. Cytologic samples were collected by nasal scraping before surgery and 1, 2, and 3 months after surgery. Ciliary motility was evaluated by nasal cytology with phase-contrast microscopy. Functional aspects of nasal mucosa were studied, with a focus on 3 parameters: (1) nasal mucociliary clearance, assessed by saccharin nasal transit time test; (2) percentage of ciliated cell motility, measured as the ratio between cells with motility and cells without motility; and (3) efficacy of ciliary motility, measured as the ratio between cells with valid motility and cells with hypovalid motility. RESULTS: Ciliary motility and ciliary efficacy showed a significant reduction after 1 and 2 months from surgery, returning to normal values within 3 months. No significant changes in saccharin nasal transit time were recorded during the follow-up. CONCLUSIONS: The outcomes of this study suggest that radiofrequency ablation treatment causes ciliary motility changes of nasal mucosa that are completely restored after at least 3 months after surgery. These cytologic abnormalities do not affect nasal functionality. PMID- 26861230 TI - Head and Neck Paragangliomas: An Update on Evaluation and Management. AB - OBJECTIVE: Head and neck paragangliomas are a group of slow-growing hypervascular tumors associated with the paraganglion system. The approach to evaluate and treat these lesions has evolved over the last 2 decades. While radical surgery had been the traditional approach, improvements in diagnostic imaging as well as radiation therapy techniques have led to an emphasis on observation and nonsurgical therapy in many patients. This article reviews the contemporary approach to the workup and management of head and neck paragangliomas. DATA SOURCE: Articles were identified from PubMed. REVIEW METHODS: PubMed searches with the following keywords were performed: carotid body paraganglioma management, vagal paraganglioma management, jugulotympanic paraganglioma management, imaging of head and neck paragangliomas, head and neck paraganglioma embolization, paraganglioma radiation, head and neck paraganglioma management, observation of head and neck paragangliomas, bilateral carotid body paragangliomas, and genetics of paragangliomas. Review and original research articles available in the English language and published during or after 2009 were selected on the basis of their clinical relevance and scientific strength. Certain articles published prior to 2009 were also included if they provided background information that was relevant. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Workup and treatment of head and neck paragangliomas are changing. With more now known regarding the longitudinal behavior of these tumors, observation and nonsurgical therapy are indicated in many instances. For patients where surgery is the most appropriate option, improved diagnostic and perioperative techniques are allowing patients to tolerate resection, often with reduced morbidity. PMID- 26861229 TI - Organized Hematoma: An Analysis of 84 Cases with Emphasis on Difficult Prediction and Favorable Management. AB - OBJECTIVE: To characterize features of organized hematoma (OH) that may cause considerable diagnostic difficulties. STUDY DESIGN: Case series with chart review. SETTING: Tertiary medical center. SUBJECTS AND METHODS: Eighty-four patients with pathologically confirmed OH over a 10-year period were retrospectively reviewed for clinical features, imaging findings, pathologic characteristics, and treatment modalities. RESULTS: This study included 39 males and 45 females who presented with frequent epistaxis and nasal obstruction. There were 62 (74%) patients >40 years old (mean, 50; range, 9-81). OH mainly originated in the maxillary sinus (n = 82) or nasal cavity (n = 2) unilaterally, and most were expansile masses (n = 73) that extended into nasal cavity (n = 71) or choanae (n = 17). Several lesions were locally aggressive and simulated a malignant process that involved the ethmoid sinus (n = 22), orbit (n = 11), pterygopalatine fossa (n = 16), infratemporal fossa (n = 9), cheek (n = 3), and hard palate (n = 3). Internal architecture on computed tomography (CT) scans showed OH with expansile remodeling of the maxillary wall (82.1%) and smooth bony destruction (70.2%), whereas T2-weighted magnetic resonance (MR) images showed inhomogeneity with a notable hypointense peripheral rim in all lesions. CT and MR contrast-enhanced images revealed patchy heterogeneous enhancement that could be interpreted according to histopathologic findings of hemorrhage and neovascularization. OH was successfully removed with endoscopic surgery, although 5 cases recurred. CONCLUSIONS: OH can be successfully treated by endoscopic surgery. CT and MR examination provide characteristic findings for prediction and careful surgical planning. PMID- 26861231 TI - Definitive Surgical Therapy after Open Neck Biopsy for HPV-Related Oropharyngeal Cancer. AB - OBJECTIVE: To determine the impact of prior open neck biopsy on the prognosis of patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) who are subsequently treated with a definitive surgical paradigm, including adjuvant therapy when indicated. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary care university hospital. SUBJECTS AND METHODS: Patients with open neck biopsies who were treated with definitive surgery, with or without adjuvant therapy, for HPV-related OPSCC between 1998 and 2012 were compared with a matched control group who did not undergo open neck biopsy. Outcomes were disease-free survival, overall survival, disease-specific survival, incidence of tumor deposit in dermal scar, patterns of recurrence, and neck dissection complications. RESULTS: Forty-five patients who underwent open neck biopsy were compared with 90 matched controls. Tumor deposits in dermal scars from the prior open neck biopsy were found in 3 patients (7%) during completion neck dissection. Overall complications of the neck dissection were not significantly increased in the open biopsy group over matched controls (20% vs 12%, respectively; P > .05). Five-year Kaplan-Meier estimates for disease-free survival, overall survival, and disease-specific survival were not significantly different between the open biopsy and control groups (93% vs 91%, 98% vs 97%, 98% vs 99%, respectively; all P > .05). Recurrence rates were also not significantly different between groups. CONCLUSIONS: Patients with HPV-related OPSCC who have undergone a prior open neck biopsy can be successfully treated with a definitive surgical paradigm. Although needle biopsy is preferable to establish a diagnosis, previous open neck biopsy does not affect prognosis in these patients. PMID- 26861232 TI - Application of Lean Sigma to the Audiology Clinic at a Large Academic Center. AB - OBJECTIVE: To apply Lean Sigma--a quality improvement strategy to eliminate waste and reduce variation and defects--to improve audiology scheduling and utilization in a large tertiary care referral center. The project goals included an increase in utilization rates of audiology block time and a reduction in appointment lead time. STUDY DESIGN: Prospective quality improvement study. SETTING: Academic tertiary care center. SUBJECTS: All patients scheduling audiology clinic visits July 2013 to July 2014. METHODS: Value stream mapping was performed for the audiology scheduling process, and wasteful steps were identified for elimination. Interventions included a 2-week block release, audiology template revision, and reduction of underutilized blocks. Schedule utilization and lead time for new patient diagnostic audiogram were measured for 5 months postintervention and compared with 5 months preintervention. Overall, 2995 preintervention and 3714 postintervention booked appointments were analyzed. RESULTS: Block utilization increased from 77% to 90% after intervention (P < .0001). Utilization of joint with-provider visits increased from 39% to 67% (P < .0001). Booked appointments increased from 2995 to 3714, with joint-with-provider booked appointments increasing from 317 to 1193. Appointment lead time averaged 24 days postintervention, compared with 29 days preintervention (P = .06). Average monthly relative value units measured 13,321 preintervention and 14,778 postintervention (P = .09). CONCLUSION: Lean Sigma techniques were successfully used to increase appointment block utilization and streamline scheduling practices. PMID- 26861233 TI - Repair of Posterior Glottic Stenosis with the Modified Endoscopic Postcricoid Advancement Flap. AB - Posterior glottic stenosis is a difficult clinical problem that frequently results in bilateral vocal fold immobility, dyspnea, and tracheostomy dependence. Charts were reviewed of all patients undergoing a modified endoscopic postcricoid advancement flap procedure for posterior glottic stenosis between October 1, 2003, and June 30, 2015. Age, sex, operative findings, complications, and outcomes were noted. Follow-up was available in 10 of 11 patients, 10 of whom were successfully decannulated. There were no complications. Regular diet was maintained in all patients. In patients with bilateral vocal fold immobility secondary to posterior glottis stenosis, endoscopic repair via endoscopic postcricoid advancement flap can restore full vocal fold motion and allow decannulation. In select patients with posterior glottic stenosis, repair via endoscopic postcricoid advancement flap should be considered in lieu of ablative methods, such as cordotomy, cordectomy, or arytenoidectomy. PMID- 26861234 TI - Mucoepidermoid Carcinoma at the Mandibular Edentulous Ridge Mucosa: An Infrequent Location. PMID- 26861235 TI - Novel Anatomic Characteristics of the Laryngeal Framework: A Computed Tomography Evaluation. AB - OBJECTIVE: The thyroid cartilage (TC) in men has a more prominent thyroid notch and a narrower interlaminae angle (ILA) as compared with women. Anatomy textbooks classically stipulate that the ILA is 90 degrees in men and 120 degrees in women. Our observation, based on thyroid chondroplasty operations, of a much narrower angle led to the current investigation. STUDY DESIGN: Cohort imaging study. SETTING: Tertiary academic referral center. SUBJECTS AND METHODS: Computed tomography angiography neck images of adult patients were studied. The ILA was measured on 2 axial planes: at the level of the vocal processes (and the upper portion of thyroarytenoid muscles) and 5 mm superior and parallel to the former. The anterior projection of the TC and the vertical dimensions of the midline cricothyroid membrane (CTM) were also measured. RESULTS: A total of 126 patients were included in the study. The average ILAs were 63.5 degrees +/-20.6 degrees and 93.3 degrees +/-16.6 degrees for men and women, respectively (P < 10(-14)), and were significantly narrower at the upper level in comparison with the vocal process level (P < 10(-7) for men, P = .004 for women). The anterior projection of the TC in men was more prominent as compared with women (P = .0003) and significantly correlated with the ILA (P = .0159). The length of the midline CTM was 11.1+/-2.3 mm in men and 10.3+/-1.7 mm in women (P = .0355). CONCLUSIONS: The ILA is narrower than that reported in the classic anatomy textbooks. In male patients, the upper part of the TC becomes narrower and projects anteriorly like a "jug's spout." The mean vertical dimension of the midline CTM was 10 to 11 mm. PMID- 26861236 TI - Features of Residual Dizziness after Canalith Repositioning Procedures for Benign Paroxysmal Positional Vertigo. AB - OBJECTIVES: To assess factors related to residual dizziness (RD) in patients who underwent successful canalith repositioning procedures (CRPs) for benign paroxysmal positional vertigo (BPPV). STUDY DESIGN: Prospective cohort study. SETTING: Academic center. SUBJECTS AND METHODS: Ninety-seven consecutive patients with BPPV of the posterior semicircular canal were initially enrolled. Diagnosis was assessed according to clinical history and bedside evaluation. All patients were treated with CRPs until nystagmus disappeared. Three days after the successful treatment, presence of RD was investigated. If RD was present, patients were monitored every 3 days until the symptoms disappeared. Subjects who required >=4 CRPs or who failed to meet the follow-up visit were excluded. The Dizziness Handicap Inventory (DHI) was obtained from patients at the time of diagnosis and at every subsequent visit. RESULTS: At the end of selection, 86 patients were included; 33 (38.36%) reported RD after successful treatment. A significant difference in the incidence of RD was observed in consideration of the age of the subjects (P = .0003) and the DHI score at the time of diagnosis (P < .001). A logistic regression analysis showed that the probability of RD occurrence increased with the increase of the emotional subdomain score of the DHI questionnaire. CONCLUSION: RD is a common self-limited disorder, more frequent in the elderly, which may occur after the physical treatment for BPPV. The DHI score at the time of BPPV diagnosis represents a useful tool to quantify the impact of this vestibular disorder on the quality of life and to estimate the risk of RD after CRPs. PMID- 26861237 TI - Editorial: Special Issue of the American Journal of Epidemiology Commemorating the Centennial of the Johns Hopkins Bloomberg School of Public Health. PMID- 26861238 TI - The Potential Trajectory of Carbapenem-Resistant Enterobacteriaceae, an Emerging Threat to Health-Care Facilities, and the Impact of the Centers for Disease Control and Prevention Toolkit. AB - Carbapenem-resistant Enterobacteriaceae (CRE), a group of pathogens resistant to most antibiotics and associated with high mortality, are a rising emerging public health threat. Current approaches to infection control and prevention have not been adequate to prevent spread. An important but unproven approach is to have hospitals in a region coordinate surveillance and infection control measures. Using our Regional Healthcare Ecosystem Analyst (RHEA) simulation model and detailed Orange County, California, patient-level data on adult inpatient hospital and nursing home admissions (2011-2012), we simulated the spread of CRE throughout Orange County health-care facilities under 3 scenarios: no specific control measures, facility-level infection control efforts (uncoordinated control measures), and a coordinated regional effort. Aggressive uncoordinated and coordinated approaches were highly similar, averting 2,976 and 2,789 CRE transmission events, respectively (72.2% and 77.0% of transmission events), by year 5. With moderate control measures, coordinated regional control resulted in 21.3% more averted cases (n = 408) than did uncoordinated control at year 5. Our model suggests that without increased infection control approaches, CRE would become endemic in nearly all Orange County health-care facilities within 10 years. While implementing the interventions in the Centers for Disease Control and Prevention's CRE toolkit would not completely stop the spread of CRE, it would cut its spread substantially, by half. PMID- 26861240 TI - Sensitivity analysis for dose deposition in radiotherapy via a Fokker-Planck model. AB - In this paper, we study the sensitivities of electron dose calculations with respect to stopping power and transport coefficients. We focus on the application to radiotherapy simulations. We use a Fokker-Planck approximation to the Boltzmann transport equation. Equations for the sensitivities are derived by the adjoint method. The Fokker-Planck equation and its adjoint are solved numerically in slab geometry using the spherical harmonics expansion ($P_N$) and an Harten Lax-van Leer finite volume method. Our method is verified by comparison to finite difference approximations of the sensitivities. Finally, we present numerical results of the sensitivities for the normalized average dose deposition depth with respect to the stopping power and the transport coefficients, demonstrating the increase in relative sensitivities as beam energy decreases. This in turn gives estimates on the uncertainty in the normalized average deposition depth, which we present. PMID- 26861239 TI - The Association of Socioeconomic Status With Subclinical Myocardial Damage, Incident Cardiovascular Events, and Mortality in the ARIC Study. AB - The association between socioeconomic status (SES) and subclinical cardiovascular disease is not well understood. Using data from the Atherosclerosis Risk in Communities Study, we sought to evaluate the cross-sectional and prospective associations of SES, measured by annual income and educational level, with elevated high-sensitivity cardiac troponin T (hs-cTnT) concentrations (>=14 ng/L) using Poisson and multinomial logistic regressions, respectively. We used Cox proportional hazard models to compare the risks of coronary heart disease, heart failure, and mortality according to SES, stratified by baseline hs-cTnT concentration. Our study baseline was 1990-1992, with follow-up through 2011. We found an independent association between SES and hs-cTnT. When comparing participants in the lowest educational level group to those in the highest, the adjusted prevalence ratios for elevated hs-cTnT were 1.36 (95% confidence interval: 1.05, 1.75) overall, 1.83 (95% confidence interval: 1.23, 2.71) in blacks, and 1.05 (95% confidence interval: 0.73, 1.52) in whites (P for interaction = 0.08). Among participants with nonelevated hs-cTnT concentrations, when comparing those in the lowest income groups to those in the highest, the adjusted hazard ratios were strongest for heart failure and death. Having elevated baseline hs-cTnT doubled the risk of heart failure and death. Persons with low SES and elevated hs-cTnT concentrations have the greatest risk of cardiovascular events, which suggests that this group should be aggressively targeted for cardiovascular risk reduction. PMID- 26861242 TI - Translating Evidence to Increase Quality and Dose of Upper Limb Therapy for Children with Unilateral Cerebral Palsy: A Pilot Study. AB - AIMS: To pilot efficacy of a tailored multifaceted implementation program to change clinical practice of occupational therapists (OTs) providing upper limb (UL) therapy for children with unilateral cerebral palsy (UCP). METHODS: This before and after study piloted a multifaceted implementation program comprising audit/feedback, barrier identification, and education. Medical chart audits were conducted prior to and 12 months after the intervention. Primary process outcomes included proportion of children with UCP with (1) goals set; (2) goals measured; (3) received contemporary motor learning approach; (4) an adequate dose (30-40 hours); and (5) measured UL outcomes. RESULTS: Three teams of OTs (n = 9) participated. Forty-three audits at baseline and 53 at 12 months postimplementation program were conducted. Average time to complete audits was 10 min and four out of the five evidence criteria had complete data extracted from files. Changes in clinical behavior included greater measurement of goals before (+17%) and after (+22%) therapy; use of constraint therapy (+38%), bimanual therapy (+26%), home programs (+14%); measurement of UL outcomes before (+29%) and after (+23%) therapy. Children receiving the target dose increased from 0 to 10%. CONCLUSIONS: A tailored multifaceted implementation program was feasible to implement and led to meaningful changes in clinical practice behavior. PMID- 26861241 TI - Effects of the enlargement of polyglutamine segments on the structure and folding of ataxin-2 and ataxin-3 proteins. AB - Spinocerebellar ataxia type 2 (SCA2) and type 3 (SCA3) are two common autosomal dominant inherited ataxia syndromes, both of which are related to the unstable expansion of trinucleotide CAG repeats in the coding region of the related ATXN2 and ATXN3 genes, respectively. The poly-glutamine (poly-Q) tract encoded by the CAG repeats has long been recognized as an important factor in disease pathogenesis and progress. In this study, using the I-TASSER method for 3D structure prediction, we investigated the effect of poly-Q tract enlargement on the structure and folding of ataxin-2 and ataxin-3 proteins. Our results show good agreement with the known experimental structures of the Josephin and UIM domains providing credence to the simulation results presented here, which show that the enlargement of the poly-Q region not only affects the local structure of these regions but also affects the structures of functional domains as well as the whole protein. The changes observed in the predicted models of the UIM domains in ataxin-3 when the poly-Q track is enlarged provide new insights on possible pathogenic mechanisms. PMID- 26861243 TI - Factors associated with glycemic control among adult patients with type 2 diabetes mellitus: a cross-sectional survey in Ethiopia. AB - BACKGROUND: Even though the prevalence of type 2 diabetes mellitus is swelling rapidly in Ethiopia, data regarding glycemic control, a key strategy for marked reduction of diabetes mellitus complications, is scant. We have assessed the status of glycemic control and its contributing factors among adult patients with type 2 diabetes mellitus. METHODS: This was a facility based cross-sectional survey of 325 adults with type 2 diabetes mellitus attending in Jimma University Teaching Hospital, South west Ethiopia. Data from all the patients were collected between February and April 2014. Glycemic level was assessed by using fasting blood glucose level, and 'poor glycemic control' was defined when fasting blood glucose level was above 130 mg/dL (7 mm/L). Analysis included both descriptive and inferential statistics, and SPSS version 20.0 was used for all analysis. RESULTS: 309 respondents were included in the survey. More than two-third (70.9 %) of the patients had poor blood glycemic control. Patients who were illiterate (AOR = 3.46, 95 % CI 1.01-11.91) and farmer (AOR = 2.47, 95 % CI 1.13-5.39) had high odds of poor glycemic control. In addition, taking combination of insulin and oral medication (AOR = 4.59, 95 % CI 1.05-20.14) and poor medication adherence (AOR = 5.08 95 % CI 2.02-12.79) associated statistically with poor glycemic control. CONCLUSION: Majority of patients had poor glycemic control. Patients with low level of education, being employed, on combinations of insulin and oral medication, and lower adherence to their medication were likely to have poor glycemic control. Education and awareness creation could be a cross cutting intervention for the significant factors. PMID- 26861244 TI - Sleep-independent off-line enhancement and time of the day effects in three forms of skill learning. AB - The role of sleep in memory and skill-learning processes is an important and widely debated issue. The current study explores the nature of the relationship between sleep and off-line improvement in three tasks for measuring different aspects of skill learning: the serial reaction time (SRT) task, which is a motor sequence learning task; the artificial grammar learning (AGL) task, testing abstract verbal sequence learning; and the weather prediction (WP) task, which is a non-sequential categorization task. Each participant was tested on one of the three tasks twice, either in a Wake condition (with a 12-h off-line period without sleep), or in a Sleep condition (with sleep). Results showed no sleep related off-line improvement throughout the three tasks in a two-session re learning design, but a sleep-independent time-based effect was found on the SRT task. No performance boost was observed in the WP and AGL tasks. Performance on the SRT showed a time of the day effect: the Sleep group outperforming the Wake group; however, this effect was restricted to overall response latencies. Taken together, no evidence was found in favor of sleep-dependent off-line enhancement in skill learning, but methodological concerns warrant further investigations. PMID- 26861245 TI - Behavioural evidence for sex differences in the overlap between subtraction and multiplication. AB - The present study aims to identify factors that may influence the dissociability of number magnitude processing and arithmetic fact retrieval at the behavioural level. To that end, we assessed both subtraction and multiplication performance in a within-subject approach and evaluated the interdependence of unit-decade integration measures on the one hand as well as sex differences in the interdependence of performance measures on the other hand. We found that subtraction items requiring borrowing (e.g. 53-29 = 24, 3 < 9) are more error prone than subtraction items not requiring borrowing (e.g. 59-23 = 34, 9 > 3), thereby demonstrating a borrowing effect, which has been suggested as a measure of unit-decade integration in subtraction. Furthermore, we observed that multiplication items with decade-consistent distractors (e.g. 6 * 4 = 28 instead of 24) are more error prone that multiplication items with decade-inconsistent distractors (e.g. 6 * 4 = 30 instead of 24), thereby demonstrating a decade consistency effect, which has been suggested as a measure of unit-decade integration in simple multiplication. However, the borrowing effect in subtraction was not correlated with the effect of decade consistency in simple multiplication in either men or women. This indicates that unit-decade integration arises from different systems in subtraction and multiplication. Nevertheless, men outperformed women not only in subtraction, but also in multiplication. Furthermore, subtraction and multiplication performance on correct solution probes were correlated in women, but unrelated in men. Thus, the view of differential systems for number magnitude processing and arithmetic fact retrieval may not be universal across sexes. PMID- 26861247 TI - Bortezomib Inhibits Giant Cell Tumor of Bone through Induction of Cell Apoptosis and Inhibition of Osteoclast Recruitment, Giant Cell Formation, and Bone Resorption. AB - Giant cell tumor of bone (GCTB) is a rare and highly osteolytic bone tumor that usually leads to an extensive bone lesion. The purpose of this study was to discover novel therapeutic targets and identify potential agents for treating GCTB. After screening the serum cytokine profiles in 52 GCTB patients and 10 normal individuals using the ELISA assay, we found that NF-kappaB signaling related cytokines, including TNFalpha, MCP-1, IL1alpha, and IL17A, were significantly increased in GCTB patients. The results were confirmed by IHC that the expression and activity of p65 were significantly increased in GCTB patients. Moreover, all of the NF-kappaB inhibitors tested suppressed GCTB cell growth, and bortezomib (Velcade), a well-known proteasome inhibitor, was the most potent inhibitor in blocking GCTB cells growth. Our results showed that bortezomib not only induced GCTB neoplastic stromal cell (NSC) apoptosis, but also suppressed GCTB NSC-induced giant cell differentiation, formation, and resorption. Moreover, bortezomib specifically suppressed GCTB NSC-induced preosteoclast recruitment. Furthermore, bortezomib ameliorated GCTB cell-induced bone destruction in vivo As a result, bortezomib suppressed NF-kappaB-regulated gene expression in GCTB NSC apoptosis, monocyte migration, angiogenesis, and osteoclastogenesis. Particularly, the inhibitory effects of bortezomib were much better than zoledronic acid, a drug currently used in treating GCTB, in our in vitro experimental paradigms. Together, our results demonstrated that NF-kappaB signaling pathway is highly activated in GCTB, and bortezomib could suppress GCTB and osteolysis in vivo and in vitro, indicating that bortezomib is a potential agent in the treatment of GCTB. Mol Cancer Ther; 15(5); 854-65. (c)2016 AACR. PMID- 26861246 TI - Gaseous nitric oxide to treat antibiotic resistant bacterial and fungal lung infections in patients with cystic fibrosis: a phase I clinical study. AB - BACKGROUND: Individuals with cystic fibrosis (CF) receive antibiotics continuously throughout their entire life which leads to drug resistant microbial lung infections which are difficult to treat. Nitric oxide (NO) gas possesses antimicrobial activity against a wide variety of microorganisms in vitro, in vivo in animal models and a phase I study in healthy adults showed administration of intermittent 160 ppm NO to be safe. METHODS: We assessed feasibility and safety of inhaled NO in eight CF patients who received 160 ppm NO for 30 min, three times daily for 2 periods of 5 days. RESULTS: The NO treatment was safe and in none of the patients were serious drug-related adverse events observed which caused termination of the study. The intention-to-treat analysis revealed a significant mean reduction of the colony forming units of all bacteria and all fungi, while mean forced expiratory volume 1 s % predicted (FEV1) relative to baseline increased 17.3 +/- 8.9 % (P = 0.012). CONCLUSIONS: NO treatment may improve the therapy of chronic microbial lung infections in CF patients, particularly concerning pathogens with intrinsic or acquired resistance to antibiotics. PMID- 26861248 TI - Oncolytic Adenovirus Loaded with L-carnosine as Novel Strategy to Enhance the Antitumor Activity. AB - Oncolytic viruses are able to specifically replicate, infect, and kill only cancer cells. Their combination with chemotherapeutic drugs has shown promising results due to the synergistic action of virus and drugs; the combinatorial therapy is considered a potential clinically relevant approach for cancer. In this study, we optimized a strategy to absorb peptides on the viral capsid, based on electrostatic interaction, and used this strategy to deliver an active antitumor drug. We used L-carnosine, a naturally occurring histidine dipeptide with a significant antiproliferative activity. An ad hoc modified, positively charged L-carnosine was combined with the capsid of an oncolytic adenovirus to generate an electrostatic virus-carnosine complex. This complex showed enhanced antitumor efficacy in vitro and in vivo in different tumor models. In HCT-116 colorectal and A549 lung cancer cell lines, the complex showed higher transduction ratio and infectious titer compared with an uncoated oncolytic adenovirus. The in vivo efficacy of the complex was tested in lung and colon cancer xenograft models, showing a significant reduction in tumor growth. Importantly, we investigated the molecular mechanisms underlying the effects of complex on tumor growth reduction. We found that complex induces apoptosis in both cell lines, by using two different mechanisms, enhancing viral replication and affecting the expression of Hsp27. Our system could be used in future studies also for delivery of other bioactive drugs. Mol Cancer Ther; 15(4); 651-60. (c)2016 AACR. PMID- 26861249 TI - Linalool-Incorporated Nanoparticles as a Novel Anticancer Agent for Epithelial Ovarian Carcinoma. AB - Although cytotoxic chemotherapy is widely used against epithelial ovarian cancer (EOC), adverse side effects and emergence of resistance can limit its utility. Therefore, new drugs with systemic delivery platforms are urgently needed for this disease. In this study, we developed linalool-incorporated nanoparticles (LIN-NP) as a novel anticancer agent. We prepared LIN-NPs by the self-assembly water-in-oil-in-water (w/o/w) emulsion method. LIN-NP-mediated cytotoxicity and apoptosis was assessed in EOC cells, and the role of reactive oxygen species (ROS) generation as the mechanism of action was evaluated. In addition, therapeutic efficacy of LIN-NP was assessed in cell lines and patient-derived xenograft (PDX) models for EOC. LIN-NPs had significant cytotoxicity and apoptotic activity against EOC cells, including A2780, HeyA8, and SKOV3ip1. LIN NP treatment increased apoptosis in EOC cells through ROS generation and a subsequent decrease in mitochondrial membrane potential and increase in caspase-3 levels. In addition, 100 mg/kg LIN-NPs significantly decreased tumor weight in the HeyA8 (P < 0.001) and SKOV3ip1 (P = 0.006) in vivo models. Although treatment with 50 mg/kg LIN-NP did not decrease tumor weight compared with the control group, combination treatment with paclitaxel significantly decreased tumor weight compared with paclitaxel alone in SKOV3ip1 xenografts (P = 0.004) and the patient derived xenograft model (P = 0.020). We have developed LIN-NPs that induce ROS generation as a novel anticancer agent for EOC. These findings have broad applications for cancer therapy. Mol Cancer Ther; 15(4); 618-27. (c)2016 AACR. PMID- 26861250 TI - Future Directions to Establish Lipoprotein(a) as a Treatment for Atherosclerotic Cardiovascular Disease. AB - In both epidemiologic and genetic studies, increased levels of Lp(a) have been associated with increased risk for cardiovascular diseases as well as aortic stenosis. However, until recently, it has been difficult to lower levels of Lp(a). Diet and lifestyle have little effect on plasma levels of Lp(a) which are mainly genetically determined. Emerging therapeutic agents which have recently become available, or which are undergoing clinical trials, can significantly lower Lp(a) levels. Studies with these agents will hopefully be able to provide more direct information whether reductions in Lp(a) will reduce CVD events independently of reduction in LDL-cholesterol levels. PMID- 26861251 TI - Efficacy of Angiotensin-Converting Enzyme Inhibitors and Angiotensin-Receptor Blockers in Coronary Artery Disease without Heart Failure in the Modern Statin Era: a Meta-Analysis of Randomized-Controlled Trials. AB - PURPOSE: Current practice guidelines support the use of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARBs) in patients with coronary artery disease (CAD) without heart failure (HF). However, a number of cited trials were performed prior to the era of prevalent statin use. Our objective was to evaluate the effectiveness of ACEi and ARBs in reducing cardiovascular events as well as the impact of statin therapy. METHODS: We searched the MEDLINE and EMBASE databases for randomized-controlled trials (1/1/1980 - 8/31/2015) with ACEi or ARBs as the single intervention for patients with CAD without HF. We assessed the outcomes of non-fatal myocardial infarction (MI), stroke, cardiovascular mortality and all-cause mortality. The relationship between these outcomes and the percentages of patients on statin therapy was evaluated using meta-regression analysis. RESULTS: A total of ten ACEi trials and five ARB trials were included for analysis, with 78,761 patients followed for a mean of 36 months. Treatment with ACEi was associated with decreased non-fatal MI (RR 0.83; 95 % CI 0.75-0.91), stroke (RR 0.76; 95 % CI 0.68-0.86), cardiovascular mortality (RR 0.83; 95 % CI 0.72-0.95), and all-cause mortality (RR 0.86; 95 % CI 0.80-0.93). Treatment with ARBs was associated only with a decreased incidence of stroke (RR 0.92; 95 % CI 0.87-0.98). When adjusted for statin use, there was a trend towards an attenuated effect of ACEi in reducing cardiovascular mortality with increased use of statins (p-value = 0.063). CONCLUSION: In CAD patients without HF, ACEi, but not ARBs decreases the risk of non-fatal MI, cardiovascular mortality and all-cause mortality, while both ACEi and ARBs decrease the risk of stroke. PMID- 26861253 TI - Addressing inherited predisposition for breast cancer in transplant recipients. AB - Consideration of prophylactic mastectomy surgery following transplantation requires complex medical decision-making, and bias against elective surgery exists because of concern for post-operative complications. Prevention of cancer in transplant recipients is of utmost importance, given the risks of treating malignancy in an immunosuppressed patient. We present a patient case and review of the literature to support a thorough pre-transplantation evaluation of family history and consideration of prophylactic interventions to safeguard the quality of life of transplant recipients. J. Surg. Oncol. 2016;113:605-608. (c) 2016 Wiley Periodicals, Inc. PMID- 26861252 TI - Polyphyllin VII induces apoptosis in HepG2 cells through ROS-mediated mitochondrial dysfunction and MAPK pathways. AB - BACKGROUND: Paris polyphylla is an oriental folk medicine that has anticancer activities both in vivo and in vitro. Polyphyllin VII (PP7), a pennogenyl saponin from P. polyphylla has been found to exert strong anticancer activity. However, the underlying mechanisms are poorly understood. In the present study, the anticancer effect of polyphyllin VII against human liver cancer cells and the molecular mechanisms were investigated. METHODS: Cellular viability was measured by MTT assay. Apoptosis, intracellular reactive oxygen species (ROS) and mitochondrial membrane potential levels were evaluated using the InCell 2000 confocal microscope. The expression levels of apoptotic-related proteins were evaluated by Western blotting. RESULTS: PP7 strongly inhibited the cell growth and induced apoptosis and necrosis in hepatocellular carcinoma HepG2 cells. Meanwhile, PP7 up-regulated the levels of Bax/Bcl-2, cytochrome c, the cleaved forms of caspases-3, -8, -9, and poly (ADP-ribose) polymerase in a dose- and time dependent manner, indicating that PP7 induced apoptosis in HepG2 cells through both intrinsic and extrinsic pathways. Moreover, PP7 provoked the production of intracellular ROS and the depolarization of mitochondrial membrane potential. Further analysis showed that PP7 significantly augmented the phosphorylation of JNK, ERK and p38, the major components of mitogen-activated protein kinase (MAPK) pathways, and the expressions of tumor suppressor proteins p53 and PTEN. In addition, PP7-induced apoptosis was remarkably attenuated by MAPK inhibitors and ROS inhibitor. CONCLUSIONS: These results demonstrated that PP7 induced apoptotic cell death in HepG2 cells through both intrinsic and extrinsic pathways by promoting the generation of mitochondrial-mediated ROS and activating MAPK and PTEN/p53 pathways. PMID- 26861254 TI - The Effect of Different Water Temperatures on Retention Loss and Material Degradation of Locator Attachments. AB - PURPOSE: To examine the changes in Locator attachments after exposure to different water temperatures and cyclic loading. MATERIALS AND METHODS: Four groups of pink Locator attachments (3.0 lb. light retention replacement patrix attachments; 10 per group) were soaked for the equivalent of 5 years of use in distilled water at the following temperatures: 20 degrees C, 37 degrees C, 60 degrees C. One group was kept dry to test the effect of water. A universal testing machine was used to measure the retention force of each treated attachment during 5500 insertion and removal cycles, simulating approximately 5 years of use. The results were compared using Kruskal-Wallis one-way ANOVA by ranks. Surface changes of tested attachments were examined using scanning electron microscopy (SEM). RESULTS: The exposure to 60 degrees C water significantly increased the percentage of retention loss in Locator attachments (p < 0.05) compared to the 20 degrees C water group and significantly reduced the final retention force compared to the other groups (p < 0.05). SEM examinations revealed severe cracking and material degradation in Locator attachments after exposure to 60 degrees C water and cyclic loading, which were not evident in other groups. Cracking was observed after exposure to 60C water before cyclic loading. CONCLUSIONS: Exposure to 60 degrees C water, potentially similar to denture cleansing procedures, could cause cracking in Locator attachments. Cracking is associated with hydrolytic degradation of nylon at 60 degrees C. The change in structure could result in a significant loss of retention. PMID- 26861255 TI - Effect of monoclonal antibodies to PCSK9 on high-sensitivity C-reactive protein levels: a meta-analysis of 16 randomized controlled treatment arms. AB - AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are an emerging class of low-density lipoprotein cholesterol (LDL-C)-lowering agents. In spite of their known effects on lipids, the impact of these drugs on systemic inflammation is less known. We aimed to investigate the effect of PCSK9 inhibitors on high-sensitivity C-reactive protein (hs-CRP) levels through a meta analysis of randomized controlled trials (RCTs). METHODS: A systematic literature search of Medline, SCOPUS and Google Scholar was conducted up to December 2015 to identify RCTs assessing changes in hs-CRP concentrations during treatment with PCSK9 inhibitors. Quantitative data synthesis was performed using a random effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. RESULTS: Sixteen treatment arms, with a total of 2546 participants, were included. Random-effects meta-analysis did not show any significant effect of PCSK9 inhibitors on hs-CRP levels (WMD: 0.002 mg l(-1) , CI: -0.017, 0.021; P = 0.807; I(2) = 37.26%). This effect size was robust, not sensitive to any single study, and not affected by the type of PCSK9 inhibitor (evolocumab: WMD: 0.002 mg l(-1) , CI: -0.02, 0.02; P = 0.855; alirocumab WMD: 0.15 mg l(-1) , CI: -0.11, 0.40; P = 0.259; I(2) = 0%), or dosing frequency (biweekly: WMD: 0.13 mg l(-1) , CI: -0.20, 0.46; P = 0.433; I(2) = 55.19%; monthly: WMD: 0.003 mg l(-1) , CI: -0.01, 0.01; P = 0.59; I(2) = 0%). Random effects meta-regression did not suggest any association of changes in hs-CRP levels with changes in plasma LDL-C concentrations (P = 0.697) or cumulative dosage of the drug (P = 0.980). CONCLUSIONS: This meta-analysis of RCTs did not suggest an effect of PCSK9 inhibitors on hs-CRP concentrations. PMID- 26861256 TI - Margin to tumor thickness ratio - A predictor of local recurrence and survival in oral squamous cell carcinoma. AB - OBJECTIVES: To assess whether small oral squamous cell carcinomas (OSCC) require the same margin clearance as large tumors. We evaluated the association between the ratio of the closest margin to tumor size (MSR) and tumor thickness (MTR) with local control and survival. METHODS AND METHODS: The clinicopathologic and follow up data were obtained for 501 OSCC patients who had surgical resection with curative intent at our institution. MTR and MSR were computed and their associations with local control and survival were assessed using multivariable Cox-regression model. Survival curves were generated using the Kaplan-Meier method. RESULTS: MTR was a better predictor of disease control than MSR. MTR was a predictor of local failure (p=0.033) and disease specific death (p=0.038) after adjusting for perineural invasion, lymphovascular involvement, nodal status, and radiotherapy. A threshold MTR value of 0.3 was identified, above which the risk of local recurrence was low. CONCLUSION: The ratio of margin to tumor thickness was an independent predictor for local recurrence and disease specific death in this cohort. A MTR>0.3 can serve as a useful tool for adjuvant therapy planning as it combines tumor thickness and margin clearance, two well established prognostic factors. The minimum safe margin can be calculated by multiplying the tumor thickness by 0.3. Further prospective studies in other institutions are warranted to confirm the prognostic utility of MTR and assess the generalizability of our threshold values. PMID- 26861257 TI - The effect of Gly-Gln [beta-endorphin30-31] on morphine-evoked serotonin and GABA efflux in the nucleus accumbens of conscious rats. AB - Glycyl-L-glutamine (Gly-Gln; beta-endorphin30-31) is an endogenous dipeptide synthesized through the post-translational processing of beta-endorphin1-31. Central Gly-Gln administration inhibits the rewarding properties of morphine and attenuates morphine tolerance, dependence and withdrawal although it does not interfere with morphine analgesia. In an earlier study, we found that Gly-Gln inhibits morphine-induced dopamine efflux in the nucleus accumbens (NAc), consistent with its ability to inhibit morphine reward. To further investigate the mechanism responsible for its central effects we tested whether i.c.v. Gly Gln administration influences the rise in extracellular serotonin and GABA concentrations evoked by morphine in the NAc. Conscious rats were treated with Gly-Gln (100nmol/5MUl) or saline i.c.v. followed, 2min later, by morphine (2.5mg/kg) or saline i.p. and extracellular serotonin and GABA concentrations were analyzed by microdialysis and HPLC. Morphine administration increased extracellular serotonin and GABA concentrations significantly within 20min, as shown previously. Unexpectedly, Gly-Gln also increased extracellular serotonin concentrations significantly in control animals. Combined treatment with Gly Gln+morphine also elevated extracellular serotonin concentrations although the magnitude of the response did not differ significantly from the effect of Gly-Gln or morphine, given alone suggesting that Gly-Gln suppressed morphine induced serotonin efflux. Gly-Gln abolished the morphine-induced rise in extracellular GABA concentrations but had no effect on extracellular GABA when given alone to otherwise untreated animals. These data show that Gly-Gln stimulates NAc serotonin efflux and, together with earlier studies, support the hypothesis that Gly-Gln inhibits the rewarding effects of morphine by modulating morphine induced dopamine, GABA and serotonin efflux in the NAc. PMID- 26861258 TI - Aging-associated DNA methylation changes in middle-aged individuals: the Young Finns study. AB - BACKGROUND: Chronological aging-associated changes in the human DNA methylome have been studied by multiple epigenome-wide association studies (EWASs). Certain CpG sites have been identified as aging-associated in multiple studies, and the majority of the sites identified in various studies show common features regarding location and direction of the methylation change. However, as a whole, the sets of aging-associated CpGs identified in different studies, even with similar tissues and age ranges, show only limited overlap. In this study, we further explore and characterize CpG sites that show close relationship between their DNA methylation level and chronological age during adulthood and which bear the relationship regardless of blood cell type heterogeneity. RESULTS: In this study, with a multivariable regression model adjusted for cell type heterogeneity, we identified 1202 aging-associated CpG sites (a-CpGs, FDR < 5%), in whole blood in a population with an especially narrow age range (40 - 49 years). Repeatedly reported a-CpGs located in genes ELOVL2, FHL2, PENK and KLF14 were also identified. Regions with aging-associated hypermethylation were enriched regarding several gene ontology (GO) terms (especially in the cluster of developmental processes), whereas hypomethylated sites showed no enrichment. The genes with higher numbers of a-CpG hits were more often hypermethylated with advancing age. The comparison analysis revealed that of the 1202 a-CpGs identified in the present study, 987 were identified as differentially methylated also between nonagenarians and young adults in a previous study (The Vitality 90+ study), and importantly, the directions of changes were identical in the previous and in the present study. CONCLUSIONS: Here we report that aging-associated DNA methylation features can be identified in a middle-aged population with an age range of only 9 years. A great majority of these sites have been previously reported as aging-associated in a population aged 19 to 90 years. Aging is associated with different types of changes in DNA methylation, clock-like as well as random. We speculate that the a-CpGs identified here in a population with a narrow age-range represent clock-like changes, as they showed concordant methylation behavior in population spanning whole adulthood as well. PMID- 26861260 TI - [Peripheral arterial disease: An increasing concern in hypertensive women]. PMID- 26861259 TI - Children with recurrent pneumonia and non-cystic fibrosis bronchiectasis. AB - BACKGROUND: Recurrent pneumonia (RP) is one of the most frequent causes of pediatric non-cystic fibrosis (CF) bronchiectasis (BE) and a consequent accelerated decline in lung function. The aim of this study was to analyse the clinical records of children with RP in attempt to identify factors that may lead to an early suspicion of non-CF BE. METHODS: We recorded the demographic and clinical data, and lung function test results of children without CF attending our outpatient RP clinic between January 2009 to December 2013 who had undergone chest high-resolution computed tomography >= 8 weeks after an acute pneumonia episode and <= 6 months before enrolment. RESULTS: The study involved 42 patients with RP: 21 with and 21 without non-CF BE. The most frequent underlying diseases in both groups were chronic rhinosinusitis with post-nasal drip and recurrent wheezing (81 % and 71.4 % of those with, and 85.7 % and 71.4 % of those without BE). FEV1 and FEF25-75 values were significantly lower in the children with non CF BE than in those without (77.9 +/- 17.8 vs 96.8 +/- 12.4, p = 0.004; 69.3 +/- 25.6 vs 89.3 +/- 21.9, p = 0.048). Bronchodilator responsiveness was observed in seven children with BE (33.3 %) and two without (9.5 %; p = 0.13). CONCLUSIONS: Reduced FEV1 and FEF25-75 values seem associated with an increased risk of developing non-CF BE in children with RP. This suggests a need for further studies to confirm the diagnostic usefulness use of spirometry in such cases. PMID- 26861261 TI - Discovery of unique and ENM- specific pathophysiologic pathways: Comparison of the translocation of inhaled iridium nanoparticles from nasal epithelium versus alveolar epithelium towards the brain of rats. AB - The biokinetics of inhaled nanoparticles (NP) is more complex than that of larger particles since NP may NP deposited on the nasal mucosa of the upper respiratory tract (URT) may translocate to the olfactory bulb of the brain and also via the trigeminus (URT neuronal route); and (b) NP deposited in the lower respiratory tract (LRT) may cross the ABB into blood and enter the brain across the blood brain-barrier (BBB) or take a neuronal route from enervated tracheo-bronchial epithelia via the vagus nerve. Translocation from both - the URT and the LRT - are quantified during the first 24h after a 1-hour aerosol inhalation of 20nm sized, (192)Ir radiolabeled iridium NP by healthy adult rats using differential exposures: (I) nose-only exposure of the entire respiratory tract or (II) intratracheal (IT) inhalation of intubated and ventilated rats, thereby bypassing the URT and extrathoracic nasal passages. After nose-only exposure brain accumulation (BrAcc) is significantly nine-fold higher than after IT inhalation since the former results from both pathways (a+b) while the latter exposure comes only from pathway (b). Interestingly, there are significantly more circulating NP in blood 24h after nose-only inhalation than after IT inhalation. Distinguishing translocation from URT versus LRT estimated from the differential inhalation exposures, the former is significantly higher (8-fold) than from the LRT. Although the BrAcc fraction is rather low compared to total NP deposition after this short-term exposure, this study proofs that inhaled insoluble NP can accumulate in the brain from both - URT and LRT which may trigger and/or modulate adverse health effects in the central nervous system (CNS) during chronic exposure. PMID- 26861262 TI - Highly efficient optogenetic cell ablation in C. elegans using membrane-targeted miniSOG. AB - The genetically encoded photosensitizer miniSOG (mini Singlet Oxygen Generator) can be used to kill cells in C. elegans. miniSOG generates the reactive oxygen species (ROS) singlet oxygen after illumination with blue light. Illumination of neurons expressing miniSOG targeted to the outer mitochondrial membrane (mito miniSOG) causes neuronal death. To enhance miniSOG's efficiency as an ablation tool in multiple cell types we tested alternative targeting signals. We find that membrane targeted miniSOG allows highly efficient cell killing. When combined with a point mutation that increases miniSOG's ROS generation, membrane targeted miniSOG can ablate neurons in less than one tenth the time of mito-miniSOG. We extend the miniSOG ablation technique to non-neuronal tissues, revealing an essential role for the epidermis in locomotion. These improvements expand the utility and throughput of optogenetic cell ablation in C. elegans. PMID- 26861264 TI - Alisol F 24 Acetate Enhances Chemosensitivity and Apoptosis of MCF-7/DOX Cells by Inhibiting P-Glycoprotein-Mediated Drug Efflux. AB - Multidrug resistance (MDR) is a prime reason for numerous failed oncotherapy approaches. In the present study, we investigated whether Alisol F 24 acetate (ALI) could reverse the MDR of MCF-7/DOX cells, a multidrug-resistant human breast cancer cell line. We found that ALI was a potent P-glycoprotein (P-gp) inhibitor, in the Caco-2-monolayer cell model. ALI showed a significant and concentration-dependent cytotoxic effect on MCF-7/DOX cells in combination with doxorubicin by increasing intracellular accumulation and inducing nuclear migration of doxorubicin. However, ALI had no such effect on MCF-7 cells. In addition, ALI also promoted doxorubicin-induced early apoptosis of MCF-7/DOX cells in a time-dependent manner. These results suggest that ALI can enhance chemosensitivity of doxorubicin and reinforce its anti-cancer effect by increasing its uptake, especially inducing its nuclear accumulation in MCF-7/DOX cells. Therefore, ALI could be developed as a potential MDR-reversing agent in cancer chemotherapy in further study. PMID- 26861263 TI - A specialist herbivore pest adaptation to xenobiotics through up-regulation of multiple Cytochrome P450s. AB - The adaptation of herbivorous insects to their host plants is hypothesized to be intimately associated with their ubiquitous development of resistance to synthetic pesticides. However, not much is known about the mechanisms underlying the relationship between detoxification of plant toxins and synthetic pesticides. To address this knowledge gap, we used specialist pest Colorado potato beetle (CPB) and its host plant, potato, as a model system. Next-generation sequencing (454 pyrosequencing) was performed to reveal the CPB transcriptome. Differential expression patterns of cytochrome P450 complement (CYPome) were analyzed between the susceptible (S) and imidacloprid resistant (R) beetles. We also evaluated the global transcriptome repertoire of CPB CYPome in response to the challenge by potato leaf allelochemicals and imidacloprid. The results showed that more than half (51.2%) of the CBP cytochrome P450 monooxygenases (P450s) that are up regulated in the R strain are also induced by both host plant toxins and pesticide in a tissue-specific manner. These data suggest that xenobiotic adaptation in this specialist herbivore is through up-regulation of multiple P450s that are potentially involved in detoxifying both pesticide and plant allelochemicals. PMID- 26861265 TI - Two New Oleanane-Type Saponins with Anti-Proliferative Activity from Camellia oleifera Abel. Seed Cake. AB - Two new oleanane-type saponins, named oleiferasaponins C4 (1) and C5 (2), were isolated from Camellia oleifera Abel. seed cake residue. Their respective structures were identified as 16alpha-hydroxy-22alpha-O-angeloyl-23alpha-aldehyde 28-dihydroxymethylene-olean-12-ene-3beta-O-[beta-d-galacto-pyranosyl-(1->2)] [beta-d-glucopyranosyl-(1->2)-beta-d-galactopyranosy-(1->3)]-beta-d glucopyranosid-uronic acid methyl ester (1) and 16alpha-hydroxy-22alpha-O angeloyl-23alpha-aldehyde-28-dihydroxy-methylene-olean-12-ene-3beta-O-[beta-d galactopyranosyl-(1->2)]-[beta-d-galactopyranosyl-(1->3)]-beta-d glucopyranosiduronic acid methyl ester (2) through 1D- and 2D-NMR, HR-ESI-MS, and GC-MS spectroscopic methods. The two compounds exhibited potent cytotoxic activities against five human tumor cell lines (BEL-7402, BGC-823, MCF-7, HL-60 and KB). PMID- 26861266 TI - Design, Synthesis and Anticancer Evaluation of Novel Quinazoline-Sulfonamide Hybrids. AB - By combining the structural features of quinazoline and sulfonamides, novel hybrid compounds 2-21 were synthesized using a simple and convenient method. Evaluation of these compounds against different cell lines identified compounds 7 and 17 as most active anticancer agents as they showed effectiveness on the four tested cell lines. The anticancer screening results of the tested compounds provides an encouraging framework that could lead to the development of potent new anticancer agents. PMID- 26861267 TI - Peltomexicanin, a Peltogynoid Quinone Methide from Peltogyne Mexicana Martinez Purple Heartwood. AB - Peltomexicanin (7,10-dihydroxy-6,12-dioxa-5H-tetraphen-3-one) is a new peltogynoid quinone methide isolated from Palo Morado (Peltogyne mexicana Martinez) heartwood by column chromatography. Its chemical structure was elucidated by IR, NMR (1H, (13)C), 2D NMR experiments (COSY, NOESY, HMQC, and HSQC), ESI-MS, and UV-Vis spectroscopic analysis. According to HPLC quantification, this compound is the main pigment and accounts for 1.21% of Palo Morado heartwood material. The antioxidant activity of peltomexicanin and dried methanolic extract (DEx) of purple heartwood was evaluated using the radical of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay, and the corresponding values expressed as Trolox equivalents (umol TE/mg sample) were 4.25 and 4.57, respectively. PMID- 26861268 TI - 1,3-Dipolar Cycloaddition in the Preparation of New Fused Heterocyclic Compounds via Thermal Initiation. AB - This paper describes the synthesis of precursors with a benzo[b]furan skeleton for the intramolecular 1,3-dipolar cycloaddition of azomethine ylides prepared from N-substituted 3-allyl-aminobenzo[b]furan-2-aldehydes and secondary amines derived from alpha-amino acid esters. Reactions were initiated by heating. The products consisted of four fused rings with three stereogenic centers. Their structure and stereochemistry were determined by NMR spectra and X-ray measurements. PMID- 26861269 TI - Antioxidant and DNA Damage Protecting Activity of Exopolysaccharides from the Endophytic Bacterium Bacillus cereus SZ1. AB - An endophytic bacterium was isolated from the Chinese medicinal plant Artemisia annua L. The phylogenetic and physiological characterization indicated that the isolate, strain SZ-1, was Bacillus cereus. The endophyte could produce an exopolysaccharide (EPS) at 46 mg/L. The 1,1-diphenyl-2-picrylhydracyl (DPPH) radical scavenging activity of the EPS reached more than 50% at 3-5 mg/mL. The EPS was also effective in scavenging superoxide radical in a concentration dependent fashion with an EC50 value of 2.6 mg/mL. The corresponding EC50 for scavenging hydroxyl radical was 3.1 mg/mL. Moreover, phenanthroline-copper complex-mediated chemiluminescent emission of DNA damage was both inhibited and delayed by EPS. The EPS at 0.7-1.7 mg/mL also protected supercoiled DNA strands in plasmid pBR322 against scission induced by Fenton-mediated hydroxyl radical. The preincubation of PC12 cells with the EPS prior to H2O2 exposure increased the cell survival and glutathione (GSH) level and catalase (CAT) activities, and decreased the level of malondialdehyde (MDA) and lactate dehydrogenase (LDH) activity in a dose-dependent manner, suggesting a pronounced protective effect against H2O2-induced cytotoxicity. Our study indicated that the EPS could be useful for preventing oxidative DNA damage and cellular oxidation in pharmaceutical and food industries. PMID- 26861270 TI - Theoretical Study of Molecular Structure and Physicochemical Properties of Novel Factor Xa Inhibitors and Dual Factor Xa and Factor IIa Inhibitors. AB - The geometries and energies of factor Xa inhibitors edoxaban, eribaxaban, fidexaban, darexaban, letaxaban, and the dual factor Xa and thrombin inhibitors tanogitran and SAR107375 in both the gas-phase and aqueous solution were studied using the Becke3LYP/6-31++G(d,p) or Grimme's B97D/6-31++G(d,p) method. The fully optimized conformers of these anticoagulants show a characteristic l-shape structure, and the water had a remarkable effect on the equilibrium geometry. According to the calculated pKa values eribaxaban and letaxaban are in neutral undissociated form at pH 7.4, while fidexaban and tanogitran exist as zwitterionic structures. The lipophilicity of the inhibitors studied lies within a large range of log P between 1 and 4. The dual inhibitor SAR107375 represents an improvement in structural, physicochemical and pharmacokinetic characteristics over tanogitran. At blood pH, SAR107375 predominantly exists in neutral form. In contrast with tanogitran, it is better absorbed and more lipophilic and active after oral application. PMID- 26861271 TI - Cellular Uptake and Photo-Cytotoxicity of a Gadolinium(III)-DOTA-Naphthalimide Complex "Clicked" to a Lipidated Tat Peptide. AB - A new bifunctional macrocyclic chelator featuring a conjugatable alkynyl naphthalimide fluorophore pendant group has been prepared and its Gd(III) complex coupled to a cell-penetrating lipidated azido-Tat peptide derivative using Cu(I) catalysed "click" chemistry. The resulting fluorescent conjugate is able to enter CAL-33 tongue squamous carcinoma cells, as revealed by confocal microscopy, producing a very modest anti-proliferative effect (IC50 = 93 uM). Due to the photo-reactivity of the naphthalimide moiety, however, the conjugate's cytotoxicity is significantly enhanced (IC50 = 16 uM) upon brief low-power UV-A irradiation. PMID- 26861272 TI - The Anti-Atherosclerotic Effect of Naringin Is Associated with Reduced Expressions of Cell Adhesion Molecules and Chemokines through NF-kappaB Pathway. AB - Naringin has been reported to have an anti-atherosclerosis effect but the underlying mechanism is not fully understood. The aim of this study is to investigate the impact of naringin on the TNF-alpha-induced expressions of cell adhesion molecules, chemokines and NF-kappaB signaling pathway in human umbilical vein endothelial cells (HUVECs). The experiments revealed that naringin, at concentrations without cytotoxicity, dose-dependently inhibited the adhesion of THP-1 monocytes to the TNF-alpha-stimulated HUVECs. The TNF-alpha-induced expressions of cell adhesion molecules, including VCAM-1, ICAM-1 and E-selectin, at both the mRNA and protein levels, were significantly suppressed by naringin in a dose dependent manner. In addition, the TNF-alpha-induced mRNA and protein levels of chemokines, including fractalkine/CX3CL1, MCP-1 and RANTES, were also reduced by naringin. Naringin significantly inhibited TNF-alpha-induced nuclear translocation of NF-kappaB, which resulted from the inhibited phosphorylation of IKKalpha/beta, IkappaB-alpha and NF-kappaB. Altogether, we proposed that naringin modulated TNF-alpha-induced expressions of cell adhesion molecules and chemokines through the inhibition of TNF-alpha-induced activation of IKK/NF-kappaB signaling pathway to exert the anti-atherosclerotic effect. PMID- 26861273 TI - Novel Triazole-Quinoline Derivatives as Selective Dual Binding Site Acetylcholinesterase Inhibitors. AB - Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide. Currently, the only strategy for palliative treatment of AD is to inhibit acetylcholinesterase (AChE) in order to increase the concentration of acetylcholine in the synaptic cleft. Evidence indicates that AChE also interacts with the beta-amyloid (Abeta) protein, acting as a chaperone and increasing the number and neurotoxicity of Abeta fibrils. It is known that AChE has two binding sites: the peripheral site, responsible for the interactions with Abeta, and the catalytic site, related with acetylcholine hydrolysis. In this work, we reported the synthesis and biological evaluation of a library of new tacrine-donepezil hybrids, as a potential dual binding site AChE inhibitor, containing a triazole quinoline system. The synthesis of hybrids was performed in four steps using the click chemistry strategy. These compounds were evaluated as hAChE and hBChE inhibitors, and some derivatives showed IC50 values in the micro-molar range and were remarkably selective towards hAChE. Kinetic assays and molecular modeling studies confirm that these compounds block both catalytic and peripheral AChE sites. These results are quite interesting since the triazole-quinoline system is a new structural scaffold for AChE inhibitors. Furthermore, the synthetic approach is very efficient for the preparation of target compounds, allowing a further fruitful new chemical library optimization. PMID- 26861274 TI - Bio-Based Solvents for Green Extraction of Lipids from Oleaginous Yeast Biomass for Sustainable Aviation Biofuel. AB - Lipid-based oleaginous microorganisms are potential candidates and resources for the sustainable production of biofuels. This study was designed to evaluate the performance of several alternative bio-based solvents for extracting lipids from yeasts. We used experimental design and simulation with Hansen solubility simulations and the conductor-like screening model for realistic solvation (COSMO RS) to simulate the solubilization of lipids in each of these solvents. Lipid extracts were analyzed by high performance thin-layer chromatography (HPTLC) to obtain the distribution of lipids classes and gas chromatography coupled with a flame ionization detector (GC/FID) to obtain fatty acid profiles. Our aim was to correlate simulation with experimentation for extraction and solvation of lipids with bio-based solvents in order to make a preliminary evaluation for the replacement of hexane to extract lipids from microorganisms. Differences between theory and practice were noted for several solvents, such as CPME, MeTHF and ethyl acetate, which appeared to be good candidates to replace hexane. PMID- 26861275 TI - New Biopolymer Nanoparticles Improve the Solubility of Lipophilic Megestrol Acetate. AB - As many substances are poorly soluble in water and thus possess decreased bioavailability, creating orally administered forms of these substances is a challenge. The objective of this study was to determine whether the solubility of megestrol acetate, a Biopharmaceutical Classification System (BCS) class II drug, can be improved by using a newly-synthesized surfactant (Rofam 70: a rapeseed methyl ester ethoxylate) and compare it with two references surfactants (Tween 80, Pluronic F68) at three different pH values. Spectrophotometry was used to compare the solubility profiles in the presence of three tested surfactants at pH 5.0, 7.4 and 9.0. Rapeseed methyl ester ethoxylate was found to improve the solubility of the BCS Class II drug and increase its bioavailability; It increased drug solubility more effectively than Pluronic F68. Its cytotoxicity results indicate its possible value as a surfactant in Medicine and Pharmacy. PMID- 26861276 TI - ROMP Synthesis of Iron-Containing Organometallic Polymers. AB - The paper overviews iron-containing polymers prepared by controlled "living" ring opening metathesis polymerization (ROMP). Developments in the design and synthesis of this class of organometallic polymers are highlighted, pinpointing methodologies and newest trends in advanced applications of hybrid materials based on polymers functionalized with iron motifs. PMID- 26861277 TI - Design of Potent and Controllable Anticoagulants Using DNA Aptamers and Nanostructures. AB - The regulation of thrombin activity offers an opportunity to regulate blood clotting because of the central role played by this molecule in the coagulation cascade. Thrombin-binding DNA aptamers have been used to inhibit thrombin activity. In the past, to address the low efficacy reported for these aptamers during clinical trials, multiple aptamers have been linked using DNA nanostructures. Here, we modify that strategy by linking multiple copies of various thrombin-binding aptamers using DNA weave tiles. The resulting constructs have very high anticoagulant activity in functional assays owing to their improved cooperative binding affinity to thrombin due to optimized spacing, orientation, and the high local concentration of aptamers. We also report the results of molecular dynamics simulations to gain insight into the solution conformations of the tiles. Moreover, by using DNA strand displacement, we were able to turn the coagulation cascade off and on as desired, thereby enabling significantly better control over blood coagulation. PMID- 26861278 TI - Biochemical Characteristics of Three Laccase Isoforms from the Basidiomycete Pleurotus nebrodensis. AB - The characterization of three laccase isoforms from Pleurotus nebrodensis is described. Isoenzymes Lac1, Lac2 and Lac3 were purified to homogeneity using ion exchange chromatography on DEAE-cellulose, CM-cellulose and Q-Sepharose and a gel filtration step on Superdex 75. The molecular weights of the purified laccases were estimated to be 68, 64 and 51 kDa, respectively. The isoenzymes demonstrated the same optimum pH at 3.0 but slightly different temperature optima: 50-60 degrees C for Lac1 and Lac3 and 60 degrees C for Lac2. Lac2 was always more stable than the other two isoforms and exposure to 50 degrees C for 120 min caused 30% loss in activity. Lac2 was relatively less stable than the other two isoforms when exposed to the pH range of 3.0-8.0 for 24 h, but inactivation only occurred initially, with around 70% residual activity being maintained during the whole process. Oxidative ability towards aromatic compounds varied substantially among the isoforms and each of them displayed preference toward some substrates. Kinetic constants (Km, Kcat) were determined by using a 2,2'-azino-bis(3 ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) assay, with Lac3 showing the best affinity and Lac2 displaying the highest catalytic efficiency. Amino acid sequences from peptides derived from digestion of isoenzymes showed great consistency with laccases in the databases. PMID- 26861279 TI - A Continuous Procedure Based on Column Chromatography to Purify Anthocyanins from Schisandra chinensis by a Macroporous Resin plus Gel Filtration Chromatography. AB - In our previous study, as natural food colorants and antioxidants, the color and content stabilities of Schisandra chinensis (S. chinensis) anthocyanins were investigated. In this work, the purification process parameters of S. chinensis anthocyanins using a macroporous resin and gel filtration chromatography were evaluated. The optimized parameters of static adsorption and desorption were as follows. The selected resin is HPD-300 (nonpolar copolymer styrene type resin), and the anthocyanins adsorption saturation capacity of HPD-300 resin was 0.475 mg/g dry resin. Adsorption time was 4 h, and 0.517 mg/mL of S. chinensis anthocyanins was adsorbed on the resin column with a flow rate of 39 mL/h (3 BV/h). After adsorption, the anthocyanins were completely desorpted with 2.5 BV of 90% (v/v) ethanol solution, and the desorption flow rate was 13 mL/h (1 BV/h). After purification by dynamic adsorption and desorption, the anthocyanins content in the effluent increased from 47.6 mg/g to 128.4 mg/g, the purity of anthocyanins increased six-fold from 5.08% to 30.43%, and the anthocyanins recovery was 96.5%. The major constituent of S. chinensis anthocyanins was isolated with Bio-Gel P2 gel filtration chromatography, and it was detected by liquid chromatography electrospray ionisation tandem mass spectrometry (LC-ESI MS) as cyanidin-3-O-xylosylrutinoside. Moreover, the antioxidant activities of S. chinensis anthocyanins were investigated. After purification using the HPD-300 resin, the antioxidant activities of anthocyanins were increased 1.2-fold (FRAP) and 1.7-fold (ABTS). PMID- 26861280 TI - Synthesis and Anticancer Activities of Glycyrrhetinic Acid Derivatives. AB - A total of forty novel glycyrrhetinic acid (GA) derivatives were designed and synthesized. The cytotoxic activity of the novel compounds was tested against two human breast cancer cell lines (MCF-7, MDA-MB-231) in vitro by the MTT method. The evaluation results revealed that, in comparison with GA, compound 42 shows the most promising anticancer activity (IC50 1.88 +/- 0.20 and 1.37 +/- 0.18 uM for MCF-7 and MDA-MB-231, respectively) and merits further exploration as a new anticancer agent. PMID- 26861281 TI - Isolation of Flavonoids from Deguelia duckeana and Their Effect on Cellular Viability, AMPK, eEF2, eIF2 and eIF4E. AB - Preparations of Deguelia duckeana, known in Brazil as timbo, are used by indigenous people to kill fish. Reinvestigation of its extracts resulted in the isolation and identification of 11 known flavonoids identified as 3,5,4' trimethoxy-4-prenylstilbene (1), 4-methoxyderricidine (2), lonchocarpine (3), 4 hydroxylonchocarpine (4), 4-methoxylonchocarpine (5), 5-hydroxy-4',7-dimethoxy-6 prenylflavanone (6), 4'-hydroxyisolonchocarpine (7), 4'-methoxyisolonchocarpine (8), 3',4',7-trimethoxyflavone (9), 3',4'-methylenedioxy-7-methoxyflavone (10), and 2,2-dimethyl-chromone-5,4'-hydroxy-5'-methoxyflavone (11). Except for 1, 3, and 4 all of these flavonoids have been described for the first time in D. duckeana and the flavanone 6 for the first time in nature. Compounds 2, 3, 4, 7, 9, and 10 were studied for their potential to induce cell death in neuronal SK-N SH cells. Only the chalcone 4 and the flavanone 7 significantly induced lactate dehydrogenase (LDH) release, which was accompanied by activation of caspase-3 and impairment of energy homeostasis in the MTT assay and may explain the killing effect on fish. Interestingly, the flavone 10 reduced cell metabolism in the MTT assay without inducing cytotoxicity in the LDH assay. Furthermore, the flavonoids 2, 3, 4, 7, and 10 induced phosphorylation of the AMP-activated protein kinase (AMPK) and the eukaryotic elongation factor 2 (eEF2). The initiation factor eIF4E was dephosphorylated in the presence of these compounds. The initiation factor eIF2alpha was not affected. Further studies are needed to elucidate the importance of the observed effects on protein synthesis and potential therapeutic perspectives. PMID- 26861282 TI - Room Temperature Ionic Liquids as Green Solvent Alternatives in the Metathesis of Oleochemical Feedstocks. AB - One of the most important areas of green chemistry is the application of environmentally friendly solvents in catalysis and synthesis. Conventional organic solvents pose a threat to the environment due to the volatility, highly flammability, toxicity and carcinogenic properties they exhibit. The recently emerged room temperature ionic liquids (RTILs) are promising green solvent alternatives to the volatile organic solvents due to their ease of reuse, non volatility, thermal stability and ability to dissolve a variety of organic and organometallic compounds. This review explores the use of RTILs as green solvent media in olefin metathesis for applications in the oleochemical industry. PMID- 26861283 TI - Use of Repetitive Sequences for Molecular and Cytogenetic Characterization of Avena Species from Portugal. AB - Genomic diversity of Portuguese accessions of Avena species--diploid A. strigosa and hexaploids A. sativa and A. sterilis--was evaluated through molecular and cytological analysis of 45S rDNA, and other repetitive sequences previously studied in cereal species--rye subtelomeric sequence (pSc200) and cereal centromeric sequence (CCS1). Additionally, retrotransposons and microsatellites targeting methodologies--IRAP (inter-retrotransposon amplified polymorphism) and REMAP (retrotransposon-microsatellite amplified polymorphism)--were performed. A very high homology was detected for ribosomal internal transcribed sequences (ITS1 and ITS2) between the species analyzed, although nucleolar organizing regions (NOR) fluorescent in situ hybridization (FISH) analysis revealed distinct number of Nor loci between diploid and hexaploid species. Moreover, morphological diversity, evidenced by FISH signals with different sizes, was observed between distinct accessions within each species. pSc200 sequences were for the first time isolated from Avena species but proven to be highly similar in all genotypes analyzed. The use of primers designed for CCS1 unraveled a sequence homologous to the Ty3/gypsy retrotransposon Cereba, that was mapped to centromeric regions of diploid and hexaploid species, being however restricted to the more related A and D haplomes. Retrotransposon-based methodologies disclosed species- and accessions specific bands essential for the accurate discrimination of all genotypes studied. Centromeric, IRAP and REMAP profiles therefore allowed accurate assessment of inter and intraspecific variability, demonstrating the potential of these molecular markers on future oat breeding programs. PMID- 26861284 TI - Drug-Induced Liver Injury Network Causality Assessment: Criteria and Experience in the United States. AB - Hepatotoxicity due to drugs, herbal or dietary supplements remains largely a clinical diagnosis based on meticulous history taking and exclusion of other causes of liver injury. In 2004, the U.S. Drug-Induced Liver Injury Network (DILIN) was created under the auspices of the U.S. National Institute of Diabetes and Digestive and Kidney Diseases with the aims of establishing a large registry of cases for clinical, epidemiological and mechanistic study. From inception, the DILIN has used an expert opinion process that incorporates consensus amongst three different DILIN hepatologists assigned to each case. It is the most well established, well-described and vigorous expert opinion process for DILI to date, and yet it is an imperfect standard. This review will discuss the DILIN expert opinion process, its strengths and weaknesses, psychometric performance and future. PMID- 26861285 TI - Canine Models for Copper Homeostasis Disorders. AB - Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted. PMID- 26861286 TI - GLP-2 Attenuates LPS-Induced Inflammation in BV-2 Cells by Inhibiting ERK1/2, JNK1/2 and NF-kappaB Signaling Pathways. AB - The pathogenesis of Parkinson's disease (PD) often involves the over-activation of microglia. Over-activated microglia could produce several inflammatory mediators, which trigger excessive inflammation and ultimately cause dopaminergic neuron damage. Anti-inflammatory effects of glucagon-like peptide-2 (GLP-2) in the periphery have been shown. Nonetheless, it has not been illustrated in the brain. Thus, in this study, we aimed to understand the role of GLP-2 in microglia activation and to elucidate the underlying mechanisms. BV-2 cells were pretreated with GLP-2 and then stimulated by lipopolysaccharide (LPS). Cells were assessed for the responses of pro-inflammatory enzymes (iNOS and COX-2) and pro inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha); the related signaling pathways were evaluated by Western blotting. The rescue effect of GLP-2 on microglia-mediated neurotoxicity was also examined. The results showed that GLP-2 significantly reduced LPS-induced production of inducible nitric oxide synthase (iNOS), cyclooxygenase-s (COX-2), IL-1beta, IL-6 and TNF-alpha. Blocking of Galphas by NF449 resulted in a loss of this anti-inflammatory effect in BV-2 cells. Analyses in signaling pathways demonstrated that GLP-2 reduced LPS-induced phosphorylation of ERK1/2, JNK1/2 and p65, while no effect was observed on p38 phosphorylation. In addition, GLP-2 could suppress microglia-mediated neurotoxicity. All results imply that GLP-2 inhibits LPS-induced microglia activation by collectively regulating ERK1/2, JNK1/2 and p65. PMID- 26861287 TI - Biological and Chemical Removal of Primary Cilia Affects Mechanical Activation of Chondrogenesis Markers in Chondroprogenitors and Hypertrophic Chondrocytes. AB - Chondroprogenitors and hypertrophic chondrocytes, which are the first and last stages of the chondrocyte differentiation process, respectively, are sensitive to mechanical signals. We hypothesize that the mechanical sensitivity of these cells depends on the cell surface primary cilia. To test this hypothesis, we removed the primary cilia by biological means with transfection with intraflagellar transport protein 88 (IFT88) siRNA or by chemical means with chloral hydrate treatment. Transfection of IFT88 siRNA significantly reduced the percentage of ciliated cells in both chondroprogenitor ATDC5 cells as well as primary hypertrophic chondrocytes. Cyclic loading (1 Hz, 10% matrix deformation) of ATDC5 cells in three-dimensional (3D) culture stimulates the mRNA levels of chondrogenesis marker Type II collagen (Col II), hypertrophic chondrocyte marker Type X collagen (Col X), and a molecular regulator of chondrogenesis and chondrocyte hypertrophy bone morphogenetic protein 2 (BMP-2). The reduction of ciliated chondroprogenitors abolishes mechanical stimulation of Col II, Col X, and BMP-2. In contrast, cyclic loading stimulates Col X mRNA levels in hypertrophic chondrocytes, but not those of Col II and BMP-2. Both biological and chemical reduction of ciliated hypertrophic chondrocytes reduced but failed to abolish mechanical stimulation of Col X mRNA levels. Thus, primary cilia play a major role in mechanical stimulation of chondrogenesis and chondrocyte hypertrophy in chondroprogenitor cells and at least a partial role in hypertrophic chondrocytes. PMID- 26861288 TI - Understanding the Heat Shock Response in the Sea Cucumber Apostichopus japonicus, Using iTRAQ-Based Proteomics. AB - The sea cucumber Apostichopus japonicus is exploited as a commercial species owing to their high nutritive and medicinal value. Recent high summer temperatures have caused high mortality rates in A. japonicus. In this study, we applied the isobaric tag for relative and absolute quantitation (iTRAQ) technique to investigate the global protein expression profile under an acute short-term (48 h) heat stress. In total, 3432 proteins were identified, and 127 proteins showed significant heat stress responses, with 61 upregulated proteins and 66 downregulated proteins. Our results suggest that heat stress influenced the expression of proteins involved in various biological processes, such as tissue protection and detoxification, lipid and amino acid metabolism, energy production and usage, transcription and translation, cell apoptosis, and cell proliferation. These findings provide a better understanding about the response and thermo tolerance mechanisms of A. japonicus under heat stress. PMID- 26861291 TI - Identification of Predictive Markers for Response to Neoadjuvant Chemoradiation in Rectal Carcinomas by Proteomic Isotope Coded Protein Label (ICPL) Analysis. AB - Neoadjuvant chemoradiation (nCRT) is an established procedure in stage union internationale contre le cancer (UICC) II/III rectal carcinomas. Around 53% of the tumours present with good tumor regression after nCRT, and 8%-15% are complete responders. Reliable selection markers would allow the identification of poor or non-responders prior to therapy. Tumor biopsies were harvested from 20 patients with rectal carcinomas, and stored in liquid nitrogen prior to therapy after obtaining patients' informed consent (Erlangen-No.3784). Patients received standardized nCRT with 5-Fluoruracil (nCRT I) or 5-Fluoruracil +/- Oxaliplatin (nCRT II) according to the CAO/ARO/AIO-04 protocol. After surgery, regression grading (Dworak) of the tumors was performed during histopathological examination of the specimens. Tumors were classified as poor (Dworak 1 + 2) or good (Dworak 3 + 4) responders. Laser capture microdissection (LCM) for tumor enrichment was performed on preoperative biopsies. Differences in expressed proteins between poor and good responders to nCRT I and II were identified by proteomic analysis (Isotope Coded Protein Label, ICPLTM) and selected markers were validated by immunohistochemistry. Tumors of 10 patients were classified as histopathologically poor (Dworak 1 or 2) and the other 10 tumor samples as histopathologically good (Dworak 3 or 4) responders to nCRT after surgery. Sufficient material in good quality was harvested for ICPL analysis by LCM from all biopsies. We identified 140 differentially regulated proteins regarding the selection criteria and the response to nCRT. Fourteen of these proteins were synchronously up-regulated at least 1.5-fold after nCRT I or nCRT II (e.g., FLNB, TKT, PKM2, SERINB1, IGHG2). Thirty-five proteins showed a complete reciprocal regulation (up or down) after nCRT I or nCRT II and the rest was regulated either according to nCRT I or II. The protein expression of regulated proteins such as PLEC1, TKT, HADHA and TAGLN was validated successfully by immunohistochemistry. ICPL is a valid method to identify differentially expressed proteins in rectal carcinoma tissue between poor vs. good responders to nCRT. The identified protein markers may act as selection criteria for nCRT in the future, but our preliminary findings must be reproduced and validated in a prospective cohort. PMID- 26861292 TI - Microwave-Assisted Synthesis of Glycoconjugates by Transgalactosylation with Recombinant Thermostable beta-Glycosidase from Pyrococcus. AB - The potential of the hyperthermophilic beta-glycosidase from Pyrococcus woesei (DSM 3773) for the synthesis of glycosides under microwave irradiation (MWI) at low temperatures was investigated. Transgalactosylation reactions with beta-N acetyl-d-glucosamine as acceptor substrate (GlcNAc-linker-tBoc) under thermal heating (TH, 85 degrees C) and under MWI at 100 and 300 W resulted in the formation of (Galbeta(1,4)GlcNAc-linker-tBoc) as the main product in all reactions. Most importantly, MWI at temperatures far below the temperature optimum of the hyperthermophilic glycosidase led to higher product yields with only minor amounts of side products beta(1,6-linked disaccharide and trisaccharides). At high acceptor concentrations (50 mM), transgalactosylation reactions under MWI at 300 W gave similar product yields when compared to TH at 85 degrees C. In summary, we demonstrate that MWI is useful as a novel experimental set-up for the synthesis of defined galacto-oligosaccharides. In conclusion, glycosylation reactions under MWI at low temperatures have the potential as a general strategy for regioselective glycosylation reactions of hyperthermophilic glycosidases using heat-labile acceptor or donor substrates. PMID- 26861290 TI - Argonaute and Argonaute-Bound Small RNAs in Stem Cells. AB - Small RNAs are essential for a variety of cellular functions. Argonaute (AGO) proteins are associated with all of the different classes of small RNAs, and are indispensable in small RNA-mediated regulatory pathways. AGO proteins have been identified in various types of stem cells in diverse species from plants and animals. This review article highlights recent progress on how AGO proteins and AGO-bound small RNAs regulate the self-renewal and differentiation of distinct stem cell types, including pluripotent, germline, somatic, and cancer stem cells. PMID- 26861289 TI - Genetic and Transcriptomic Profiles of Inflammation in Neurodegenerative Diseases: Alzheimer, Parkinson, Creutzfeldt-Jakob and Tauopathies. AB - Polymorphisms in certain inflammatory-related genes have been identified as putative differential risk factors of neurodegenerative diseases with abnormal protein aggregates, such as sporadic Alzheimer's disease (AD) and sporadic Parkinson's disease (sPD). Gene expression studies of cytokines and mediators of the immune response have been made in post-mortem human brain samples in AD, sPD, sporadic Creutzfeldt-Jakob disease (sCJD) subtypes MM1 and VV2, Pick's disease (PiD), progressive supranuclear palsy (PSP) and frontotemporal lobar degeneration linked to mutation P301L in MAPT Frontotemporal lobar degeneration-tau (FTLD tau). The studies have disclosed variable gene regulation which is: (1) disease dependent in the frontal cortex area 8 in AD, sPD, sCJD MM1 and VV2, PiD, PSP and FTLD-tau; (2) region-dependent as seen when comparing the entorhinal cortex, orbitofrontal cortex, and frontal cortex area 8 (FC) in AD; the substantia nigra, putamen, FC, and angular gyrus in PD, as well as the FC and cerebellum in sCJD; (3) genotype-dependent as seen considering sCJD MM1 and VV2; and (4) stage dependent as seen in AD at different stages of disease progression. These observations show that regulation of inflammation is much more complicated and diverse than currently understood, and that new therapeutic approaches must be designed in order to selectively act on specific targets in particular diseases and at different time points of disease progression. PMID- 26861293 TI - Ferritin Assembly in Enterocytes of Drosophila melanogaster. AB - Ferritins are protein nanocages that accumulate inside their cavity thousands of oxidized iron atoms bound to oxygen and phosphates. Both characteristic types of eukaryotic ferritin subunits are present in secreted ferritins from insects, but here dimers between Ferritin 1 Heavy Chain Homolog (Fer1HCH) and Ferritin 2 Light Chain Homolog (Fer2LCH) are further stabilized by disulfide-bridge in the 24 subunit complex. We addressed ferritin assembly and iron loading in vivo using novel transgenic strains of Drosophila melanogaster. We concentrated on the intestine, where the ferritin induction process can be controlled experimentally by dietary iron manipulation. We showed that the expression pattern of Fer2LCH Gal4 lines recapitulated iron-dependent endogenous expression of the ferritin subunits and used these lines to drive expression from UAS-mCherry-Fer2LCH transgenes. We found that the Gal4-mediated induction of mCherry-Fer2LCH subunits was too slow to effectively introduce them into newly formed ferritin complexes. Endogenous Fer2LCH and Fer1HCH assembled and stored excess dietary iron, instead. In contrast, when flies were genetically manipulated to co-express Fer2LCH and mCherry-Fer2LCH simultaneously, both subunits were incorporated with Fer1HCH in iron-loaded ferritin complexes. Our study provides fresh evidence that, in insects, ferritin assembly and iron loading in vivo are tightly regulated. PMID- 26861295 TI - The Effect of Small Cosolutes that Mimic Molecular Crowding Conditions on the Stability of Triplexes Involving Duplex DNA. AB - Triplex stability is studied in crowding conditions using small cosolutes (ethanol, acetonitrile and dimethylsulfoxide) by ultraviolet (UV), circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopies. The results indicate that the triplex is formed preferentially when the triplex forming oligonucleotide (TFO) is RNA. In addition, DNA triplexes (D:D.D) are clearly less stable in cosolute solutions while the stability of the RNA triplexes (R:D.D) is only slightly decreased. The kinetic of triplex formation with RNA-TFO is slower than with DNA-TFO and the thermal stability of the triplex is increased with the salt concentration in EtOH-water solutions. Accordingly, RNA could be considered a potential molecule to form a stable triplex for regulatory purposes in molecular crowding conditions. PMID- 26861294 TI - p38 MAPK Is Activated but Does Not Play a Key Role during Apoptosis Induction by Saturated Fatty Acid in Human Pancreatic beta-Cells. AB - Saturated stearic acid (SA) induces apoptosis in the human pancreatic beta-cells NES2Y. However, the molecular mechanisms involved are unclear. We showed that apoptosis-inducing concentrations of SA activate the p38 MAPK signaling pathway in these cells. Therefore, we tested the role of p38 MAPK signaling pathway activation in apoptosis induction by SA in NES2Y cells. Crosstalk between p38 MAPK pathway activation and accompanying ERK pathway inhibition after SA application was also tested. The inhibition of p38 MAPK expression by siRNA silencing resulted in a decrease in MAPKAPK-2 activation after SA application, but it had no significant effect on cell viability or the level of phosphorylated ERK pathway members. The inhibition of p38 MAPK activity by the specific inhibitor SB202190 resulted in inhibition of MAPKAPK-2 activation and noticeable activation of ERK pathway members after SA treatment but in no significant effect on cell viability. p38 MAPK overexpression by plasmid transfection produced an increase in MAPKAPK-2 activation after SA exposure but no significant influence on cell viability or ERK pathway activation. The activation of p38 MAPK by the specific activator anisomycin resulted in significant activation of MAPKAPK-2. Concerning the effect on cell viability, application of the activator led to apoptosis induction similar to application of SA (PARP cleavage and caspase-7, 8, and -9 activation) and in inhibition of ERK pathway members. We demonstrated that apoptosis-inducing concentrations of SA activate the p38 MAPK signaling pathway and that this activation could be involved in apoptosis induction by SA in the human pancreatic beta-cells NES2Y. However, this involvement does not seem to play a key role. Crosstalk between p38 MAPK pathway activation and ERK pathway inhibition in NES2Y cells seems likely. Thus, the ERK pathway inhibition by p38 MAPK activation does not also seem to be essential for SA-induced apoptosis. PMID- 26861296 TI - The Role of Cdkn1A-Interacting Zinc Finger Protein 1 (CIZ1) in DNA Replication and Pathophysiology. AB - Cdkn1A-interacting zinc finger protein 1 (CIZ1) was first identified in a yeast-2 hybrid system searching for interacting proteins of CDK2 inhibitor p21(Cip1/Waf1). Ciz1 also binds to CDK2, cyclin A, cyclin E, CDC6, PCNA, TCF4 and estrogen receptor-alpha. Recent studies reveal numerous biological functions of CIZ1 in DNA replication, cell proliferation, and differentiation. In addition, splicing variants of CIZ1 mRNA is associated with a variety of cancers and Alzheimer's disease, and mutations of the CIZ1 gene lead to cervical dystonia. CIZ1 expression is increased in cancers and rheumatoid arthritis. In this review, we will summarize the biological functions and molecular mechanisms of CIZ1 in these physiological and pathological processes. PMID- 26861297 TI - Generation of Potent Anti-Vascular Endothelial Growth Factor Neutralizing Antibodies from Mouse Phage Display Library for Cancer Therapy. AB - Vascular endothelial growth factor (VEGF) is an important stimulator for angiogenesis in solid tumors. Blocking VEGF activity is an effective therapeutic strategy to inhibit tumor growth and metastasis. Avastin, a humanized monoclonal antibody recognizes VEGF, has been approved by the US Food and Drug Administration. To generate potential VEGF-recognizing antibodies with better tumor regression ability than that of Avastin, we have designed a systematic antibody selection plan. From mice immunized with recombinant human VEGF, we generated three phage display libraries, scFv-M13KO7, Fab-M13KO7, and scFv Hyperphage, in single-chain Fv (scFv) or Fab format, displayed using either M13KO7 helper phage or Hyperphage. Solid-phase and solution-phase selection strategies were then applied to each library, generating six panning combinations. A total of sixty-four antibodies recognizing VEGF were obtained. Based on the results of epitope mapping, binding affinity, and biological functions in tumor inhibition, eight antibodies were chosen to examine their abilities in tumor regression in a mouse xenograft model using human COLO 205 cancer cells. Three of them showed improvement in the inhibition of tumor growth (328%-347% tumor growth ratio (% of Day 0 tumor volume) on Day 21 vs. 435% with Avastin). This finding suggests a potential use of these three antibodies for VEGF-targeted therapy. PMID- 26861298 TI - Active Site Mutations as a Suitable Tool Contributing to Explain a Mechanism of Aristolochic Acid I Nitroreduction by Cytochromes P450 1A1, 1A2 and 1B1. AB - Aristolochic acid I (AAI) is a plant drug found in Aristolochia species that causes aristolochic acid nephropathy, Balkan endemic nephropathy and their associated urothelial malignancies. AAI is activated via nitroreduction producing genotoxic N-hydroxyaristolactam, which forms DNA adducts. The major enzymes responsible for the reductive bioactivation of AAI are NAD(P)H: quinone oxidoreductase and cytochromes P450 (CYP) 1A1 and 1A2. Using site-directed mutagenesis we investigated the possible mechanisms of CYP1A1/1A2/1B1-catalyzed AAI nitroreduction. Molecular modelling predicted that the hydroxyl groups of serine122/threonine124 (Ser122/Thr124) amino acids in the CYP1A1/1A2-AAI binary complexes located near to the nitro group of AAI, are mechanistically important as they provide the proton required for the stepwise reduction reaction. In contrast, the closely related CYP1B1 with no hydroxyl group containing residues in its active site is ineffective in catalyzing AAI nitroreduction. In order to construct an experimental model, mutant forms of CYP1A1 and 1A2 were prepared, where Ser122 and Thr124 were replaced by Ala (CYP1A1-S122A) and Val (CYP1A2 T124V), respectively. Similarly, a CYP1B1 mutant was prepared in which Ala133 was replaced by Ser (CYP1B1-A133S). Site-directed mutagenesis was performed using a quickchange approach. Wild and mutated forms of these enzymes were heterologously expressed in Escherichia coli and isolated enzymes characterized using UV-vis spectroscopy to verify correct protein folding. Their catalytic activity was confirmed with CYP1A1, 1A2 and 1B1 marker substrates. Using (32)P-postlabelling we determined the efficiency of wild-type and mutant forms of CYP1A1, 1A2, and 1B1 reconstituted with NADPH:CYP oxidoreductase to bioactivate AAI to reactive intermediates forming covalent DNA adducts. The S122A and T124V mutations in CYP1A1 and 1A2, respectively, abolished the efficiency of CYP1A1 and 1A2 enzymes to generate AAI-DNA adducts. In contrast, the formation of AAI-DNA adducts was catalyzed by CYP1B1 with the A133S mutation. Our experimental model confirms the importance of the hydroxyl group possessing amino acids in the active center of CYP1A1 and 1A2 for AAI nitroreduction. PMID- 26861299 TI - G-Protein-Coupled Lysophosphatidic Acid Receptors and Their Regulation of AKT Signaling. AB - A hallmark of G-protein-coupled receptors (GPCRs) is their ability to recognize and respond to chemically diverse ligands. Lysophospholipids constitute a relatively recent addition to these ligands and carry out their biological functions by activating G-proteins coupled to a large family of cell-surface receptors. This review aims to highlight salient features of cell signaling by one class of these receptors, known as lysophosphatidic acid (LPA) receptors, in the context of phosphatidylinositol 3-kinase (PI3K)-AKT pathway activation. LPA moieties efficiently activate AKT phosphorylation and activation in a multitude of cell types. The interplay between LPA, its receptors, the associated Galphai/o subunits, PI3K and AKT contributes to the regulation of cell survival, migration, proliferation and confers chemotherapy-resistance in certain cancers. However, detailed information on the regulation of PI3K-AKT signals induced by LPA receptors is missing from the literature. Here, some urgent issues for investigation are highlighted. PMID- 26861300 TI - Relationship between Non-Alcoholic Fatty Liver Disease and Psoriasis: A Novel Hepato-Dermal Axis? AB - Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. In this review we discuss the rapidly expanding body of clinical and epidemiological evidence supporting a strong association between NAFLD and chronic plaque psoriasis. We also briefly discuss the possible biological mechanisms underlying this association, and discuss treatment options for psoriasis that may influence NAFLD development and progression. Recent observational studies have shown that the prevalence of NAFLD (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls, and that psoriatic patients with NAFLD have more severe psoriasis than those without NAFLD. In conclusion, the published evidence argues for more careful evaluation and surveillance of NAFLD among patients with psoriasis. PMID- 26861301 TI - Focus on Extracellular Vesicles: Introducing the Next Small Big Thing. AB - Intercellular communication was long thought to be regulated exclusively through direct contact between cells or via release of soluble molecules that transmit the signal by binding to a suitable receptor on the target cell, and/or via uptake into that cell. With the discovery of small secreted vesicular structures that contain complex cargo, both in their lumen and the lipid membrane that surrounds them, a new frontier of signal transduction was discovered. These "extracellular vesicles" (EV) were initially thought to be garbage bags through which the cell ejected its waste. Whilst this is a major function of one type of EV, i.e., apoptotic bodies, many EVs have intricate functions in intercellular communication and compound exchange; although their physiological roles are still ill-defined. Additionally, it is now becoming increasingly clear that EVs mediate disease progression and therefore studying EVs has ignited significant interests among researchers from various fields of life sciences. Consequently, the research effort into the pathogenic roles of EVs is significantly higher even though their protective roles are not well established. The "Focus on extracellular vesicles" series of reviews highlights the current state of the art regarding various topics in EV research, whilst this review serves as an introductory overview of EVs, their biogenesis and molecular composition. PMID- 26861303 TI - Focus on Extracellular Vesicles: Development of Extracellular Vesicle-Based Therapeutic Systems. AB - Many types of cells release phospholipid membrane vesicles thought to play key roles in cell-cell communication, antigen presentation, and the spread of infectious agents. Extracellular vesicles (EVs) carry various proteins, messenger RNAs (mRNAs), and microRNAs (miRNAs), like a "message in a bottle" to cells in remote locations. The encapsulated molecules are protected from multiple types of degradative enzymes in body fluids, making EVs ideal for delivering drugs. This review presents an overview of the potential roles of EVs as natural drugs and novel drug-delivery systems. PMID- 26861304 TI - Focus on Extracellular Vesicles: Exosomes and Their Role in Protein Trafficking and Biomarker Potential in Alzheimer's and Parkinson's Disease. AB - Growing evidence indicates that small extracellular vesicles, called exosomes, are prominent mediators of neurodegenerative diseases such as prion, Alzheimer's and Parkinson's disease. Exosomes contain neurodegenerative disease associated proteins such as the prion protein, beta-amyloid and alpha-synuclein. Only demonstrated so far in vivo with prion disease, exosomes are hypothesised to also facilitate the spread of beta-amyloid and alpha-synuclein from their cells of origin to the extracellular environment. In the current review, we will discuss the role of exosomes in Alzheimer's and Parkinson's disease including their possible contribution to disease propagation and pathology and highlight their utility as a diagnostic in neurodegenerative disease. PMID- 26861305 TI - Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles. AB - The intense research focus on stem and progenitor cells could be attributed to their differentiation potential to generate new cells to replace diseased or lost cells in many highly intractable degenerative diseases, such as Alzheimer disease, multiple sclerosis, and heart diseases. However, experimental and clinical studies have increasingly attributed the therapeutic efficacy of these cells to their secretion. While stem and progenitor cells secreted many therapeutic molecules, none of these molecules singly or in combination could recapitulate the functional effects of stem cell transplantations. Recently, it was reported that extracellular vesicles (EVs) could recapitulate the therapeutic effects of stem cell transplantation. Based on the observations reported thus far, the prevailing hypothesis is that stem cell EVs exert their therapeutic effects by transferring biologically active molecules such as proteins, lipids, mRNA, and microRNA from the stem cells to injured or diseased cells. In this respect, stem cell EVs are similar to EVs from other cell types. They are both primarily vehicles for intercellular communication. Therefore, the differentiating factor is likely due to the composition of their cargo. The cargo of EVs from different cell types are known to include a common set of proteins and also proteins that reflect the cell source of the EVs and the physiological or pathological state of the cell source. Hence, elucidation of the stem cell EV cargo would provide an insight into the multiple physiological or biochemical changes necessary to affect the many reported stem cell-based therapeutic outcomes in a variety of experimental models and clinical trials. PMID- 26861307 TI - Biofuel Production Based on Carbohydrates from Both Brown and Red Macroalgae: Recent Developments in Key Biotechnologies. AB - Marine macroalgae (green, red and brown macroalgae) have attracted attention as an alternative source of renewable biomass for producing both fuels and chemicals due to their high content of suitable carbohydrates and to their advantages over terrestrial biomass. However, except for green macroalgae, which contain relatively easily-fermentable glucans as their major carbohydrates, practical utilization of red and brown macroalgae has been regarded as difficult due to the major carbohydrates (alginate and mannitol of brown macroalgae and 3,6-anhydro-L galactose of red macroalgae) not being easily fermentable. Recently, several key biotechnologies using microbes have been developed enabling utilization of these brown and red macroalgal carbohydrates as carbon sources for the production of fuels (ethanol). In this review, we focus on these recent developments with emphasis on microbiological biotechnologies. PMID- 26861306 TI - Focus on Extracellular Vesicles: New Frontiers of Cell-to-Cell Communication in Cancer. AB - Extracellular Vesicles (EVs) have received considerable attention in recent years, both as mediators of intercellular communication pathways that lead to tumor progression, and as potential sources for discovery of novel cancer biomarkers. For many years, research on EVs has mainly investigated either the mechanism of biogenesis and cargo selection and incorporation, or the methods of EV isolation from available body fluids for biomarker discovery. Recent studies have highlighted the existence of different populations of cancer-derived EVs, with distinct molecular cargo, thus pointing to the possibility that the various EV populations might play diverse roles in cancer and that this does not happen randomly. However, data attributing cancer specific intercellular functions to given populations of EVs are still limited. A deeper functional, biochemical and molecular characterization of the various EV classes might identify more selective clinical markers, and significantly advance our knowledge of the pathogenesis and disease progression of many cancer types. PMID- 26861309 TI - Micellization Behavior of Long-Chain Substituted Alkylguanidinium Surfactants. AB - Surface activity and micelle formation of alkylguanidinium chlorides containing 10, 12, 14 and 16 carbon atoms in the hydrophobic tail were studied by combining conductivity and surface tension measurements with isothermal titration calorimetry. The purity of the resulting surfactants, their temperatures of Cr >LC and LC->I transitions, as well as their propensity of forming birefringent phases, were assessed based on the results of 1H and (13)C NMR, differential scanning calorimetry (DSC), and polarizing microscopy studies. Whenever possible, the resulting values of Krafft temperature (TK), critical micelle concentration (CMC), minimum surface tension above the CMC, chloride counter-ion binding to the micelle, and the standard enthalpy of micelle formation per mole of surfactant (DeltamicH degrees ) were compared to those characterizing alkyltrimethylammonium chlorides or bromides with the same tail lengths. The value of TK ranged between 292 and 314 K and increased strongly with the increase in the chain length of the hydrophobic tail. Micellization was described as both entropy and enthalpy driven. Based on the direct calorimetry measurements, the general trends in the CMC with the temperature, hydrophobic tail length, and NaCl addition were found to be similar to those of other types of cationic surfactants. The particularly exothermic character of micellization was ascribed to the hydrogen-binding capacity of the guanidinium head-group. PMID- 26861302 TI - Focus on Extracellular Vesicles: Physiological Role and Signalling Properties of Extracellular Membrane Vesicles. AB - Extracellular vesicles (EVs) are a heterogeneous population of secreted membrane vesicles, with distinct biogenesis routes, biophysical properties and different functions both in physiological conditions and in disease. The release of EVs is a widespread biological process, which is conserved across species. In recent years, numerous studies have demonstrated that several bioactive molecules are trafficked with(in) EVs, such as microRNAs, mRNAs, proteins and lipids. The understanding of their final impact on the biology of specific target cells remains matter of intense debate in the field. Also, EVs have attracted great interest as potential novel cell-free therapeutics. Here we describe the proposed physiological and pathological functions of EVs, with a particular focus on their molecular content. Also, we discuss the advances in the knowledge of the mechanisms regulating the secretion of EV-associated molecules and the specific pathways activated upon interaction with the target cell, highlighting the role of EVs in the context of the immune system and as mediators of the intercellular signalling in the brain. PMID- 26861308 TI - A Novel Feature Extraction Method with Feature Selection to Identify Golgi Resident Protein Types from Imbalanced Data. AB - The Golgi Apparatus (GA) is a major collection and dispatch station for numerous proteins destined for secretion, plasma membranes and lysosomes. The dysfunction of GA proteins can result in neurodegenerative diseases. Therefore, accurate identification of protein subGolgi localizations may assist in drug development and understanding the mechanisms of the GA involved in various cellular processes. In this paper, a new computational method is proposed for identifying cis-Golgi proteins from trans-Golgi proteins. Based on the concept of Common Spatial Patterns (CSP), a novel feature extraction technique is developed to extract evolutionary information from protein sequences. To deal with the imbalanced benchmark dataset, the Synthetic Minority Over-sampling Technique (SMOTE) is adopted. A feature selection method called Random Forest-Recursive Feature Elimination (RF-RFE) is employed to search the optimal features from the CSP based features and g-gap dipeptide composition. Based on the optimal features, a Random Forest (RF) module is used to distinguish cis-Golgi proteins from trans-Golgi proteins. Through the jackknife cross-validation, the proposed method achieves a promising performance with a sensitivity of 0.889, a specificity of 0.880, an accuracy of 0.885, and a Matthew's Correlation Coefficient (MCC) of 0.765, which remarkably outperforms previous methods. Moreover, when tested on a common independent dataset, our method also achieves a significantly improved performance. These results highlight the promising performance of the proposed method to identify Golgi-resident protein types. Furthermore, the CSP based feature extraction method may provide guidelines for protein function predictions. PMID- 26861310 TI - Hepatotoxicity by Drugs: The Most Common Implicated Agents. AB - Idiosyncratic drug-induced liver injury (DILI) is an underreported and underestimated adverse drug reaction. Information on the documented hepatotoxicity of drugs has recently been made available by a website that can be accessed in the public domain: LiverTox (http://livertox.nlm.nih.gov). According to critical analysis of the hepatotoxicity of drugs in LiverTox, 53% of drugs had at least one case report of convincing reports of liver injury. Only 48 drugs had more than 50 case reports of DILI. Amoxicillin-clavulanate is the most commonly implicated agent leading to DILI in the prospective series. In a recent prospective study, liver injury due to amoxicillin-clavulanate was found to occur in approximately one out of 2300 users. Drugs with the highest risk of DILI in this study were azathioprine and infliximab. PMID- 26861311 TI - Temporal Genetic Modifications after Controlled Cortical Impact--Understanding Traumatic Brain Injury through a Systematic Network Approach. AB - Traumatic brain injury (TBI) is a primary injury caused by external physical force and also a secondary injury caused by biological processes such as metabolic, cellular, and other molecular events that eventually lead to brain cell death, tissue and nerve damage, and atrophy. It is a common disease process (as opposed to an event) that causes disabilities and high death rates. In order to treat all the repercussions of this injury, treatment becomes increasingly complex and difficult throughout the evolution of a TBI. Using high-throughput microarray data, we developed a systems biology approach to explore potential molecular mechanisms at four time points post-TBI (4, 8, 24, and 72 h), using a controlled cortical impact (CCI) model. We identified 27, 50, 48, and 59 significant proteins as network biomarkers at these four time points, respectively. We present their network structures to illustrate the protein protein interactions (PPIs). We also identified UBC (Ubiquitin C), SUMO1, CDKN1A (cyclindependent kinase inhibitor 1A), and MYC as the core network biomarkers at the four time points, respectively. Using the functional analytical tool MetaCoreTM, we explored regulatory mechanisms and biological processes and conducted a statistical analysis of the four networks. The analytical results support some recent findings regarding TBI and provide additional guidance and directions for future research. PMID- 26861312 TI - Association between Genetic Polymorphisms and Response to Anti-TNFs in Patients with Inflammatory Bowel Disease. AB - Tumor necrosis factor (TNF) alpha is a major proinflammatory cytokine involved in the immune response in inflammatory bowel disease (IBD). Anti-TNF drugs such as infliximab and adalimumab are used to treat IBD; however, approximately 30% of patients do not respond to treatment. Individual genetic differences could contribute to lack of efficacy. Genetic studies have tried to uncover the factors underlying differences in response, however, knowledge remains limited, and the results obtained should be validated, so that pharmacogenetic information can be applied in clinical practice. In this review, we gather current knowledge in the pharmacogenetics of anti-TNF drugs in patients with IBD. We observed a connection between the major genes described as possible predictors of response to anti-TNF drugs in IBD and the cytokines and molecules involved in the T helper (Th) 17 pathway. PMID- 26861313 TI - A Classic Near-Infrared Probe Indocyanine Green for Detecting Singlet Oxygen. AB - The revelation of mechanisms of photodynamic therapy (PDT) at the cellular level as well as singlet oxygen (1O2) as a second messengers requires the quantification of intracellular 1O2. To detect singlet oxygen, directly measuring the phosphorescence emitted from 1O2 at 1270 nm is simple but limited for the low quantum yield and intrinsic efficiency of 1O2 emission. Another method is chemically trapping 1O2 and measuring fluorescence, absorption and Electron Spin Resonance (ESR). In this paper, we used indocyanine green (ICG), the only near infrared (NIR) probe approved by the Food and Drug Administration (FDA), to detect 1O2 in vitro. Once it reacts with 1O2, ICG is decomposed and its UV absorption at 780 nm decreases with the laser irradiation. Our data demonstrated that ICG could be more sensitive and accurate than Singlet Oxygen Sensor Green reagent((r)) (SOSG, a commercialized fluorescence probe) in vitro, moreover, ICG functioned with Eosin Y while SOSG failed. Thus, ICG would reasonably provide the possibility to sense 1O2 in vitro, with high sensitivity, selectivity and suitability to most photosensitizers. PMID- 26861314 TI - Exploring the Effects of Omega-3 and Omega-6 Fatty Acids on Allergy Using a HEK Blue Cell Line. AB - BACKGROUND: Allergic reactions can result in life-threatening situations resulting in high economic costs and morbidity. Therefore, more effective reagents are needed for allergy treatment. A causal relationship has been suggested to exist between the intake of omega-3/6 fatty acids, such as docosahexanoic acid (DHA), eicosapentanoic acid (EPA), docosapentanoic acid (DPA) and arachidonic acid (AA), and atopic individuals suffering from allergies. In allergic cascades, the hallmark cytokine IL-4 bind to IL-4 receptor (IL-4R) and IL-13 binds to IL-13 receptor (IL-13R), this activates the STAT6 phosphorylation pathway leading to gene activation of allergen-specific IgE antibody production by B cells. The overall aim of this study was to characterize omega-3/6 fatty acids and their effects on STAT6 signaling pathway that results in IgE production in allergic individuals. METHODS: The fatty acids were tested in vitro with a HEK Blue IL-4/IL-13 reporter cell line model, transfected with a reporter gene that produces an enzyme, secreted embryonic alkaline phosphatase (SEAP). SEAP acts as a substitute to IgE when cells are stimulated with bioactive cytokines IL-4 and/or IL-13. RESULTS: We have successfully used DHA, EPA and DPA in our studies that demonstrated a decrease in SEAP secretion, as opposed to an increase in SEAP secretion with AA treatment. A statistical Student's t-test revealed the significance of the results, confirming our initial hypothesis. CONCLUSION: We have successfully identified and characterised DHA, EPA, DPA and AA in our allergy model. While AA was a potent stimulator, DHA, EPA and DPA were potential inhibitors of IL-4R/IL-13R signalling, which regulates the STAT6 induced pathway in allergic cascades. Such findings are significant in the future design of dietary therapeutics for the treatment of allergies. PMID- 26861315 TI - Wnt16 Signaling Is Required for IL-1beta-Induced Matrix Metalloproteinase-13 Regulated Proliferation of Human Stem Cell-Derived Osteoblastic Cells. AB - We established a differentiation method for homogeneous alpha7 integrin-positive human skeletal muscle stem cell (alpha7+hSMSC)-derived osteoblast-like (alpha7+hSMSC-OB) cells, and found that interleukin (IL)-1beta induces matrix metalloproteinase (MMP)-13-regulated proliferation of these cells. These data suggest that MMP-13 plays a potentially unique physiological role in the regeneration of osteoblast-like cells. Here, we examined whether up-regulation of MMP-13 activity by IL-1beta was mediated by Wingless/int1 (Wnt) signaling and increased the proliferation of osteoblast-like cells. IL-1beta increased the mRNA and protein levels of Wnt16 and the Wnt receptor Lrp5/Fzd2. Exogenous Wnt16 was found to increase MMP-13 mRNA, protein and activity, and interestingly, the proliferation rate of these cells. Treatment with small interfering RNAs against Wnt16 and Lrp5 suppressed the IL-1beta-induced increase in cell proliferation. We revealed that a unique signaling cascade IL-1beta->Wnt16->Lrp5->MMP-13, was intimately involved in the proliferation of osteoblast-like cells, and suggest that IL-1beta-induced MMP-13 expression and changes in cell proliferation are regulated by Wnt16. PMID- 26861317 TI - An Electrochemical Impedance Spectroscopy System for Monitoring Pineapple Waste Saccharification. AB - Electrochemical impedance spectroscopy (EIS) has been used for monitoring the enzymatic pineapple waste hydrolysis process. The system employed consists of a device called Advanced Voltammetry, Impedance Spectroscopy & Potentiometry Analyzer (AVISPA) equipped with a specific software application and a stainless steel double needle electrode. EIS measurements were conducted at different saccharification time intervals: 0, 0.75, 1.5, 6, 12 and 24 h. Partial least squares (PLS) were used to model the relationship between the EIS measurements and the sugar determination by HPAEC-PAD. On the other hand, artificial neural networks: (multilayer feed forward architecture with quick propagation training algorithm and logistic-type transfer functions) gave the best results as predictive models for glucose, fructose, sucrose and total sugars. Coefficients of determination (R2) and root mean square errors of prediction (RMSEP) were determined as R2 > 0.944 and RMSEP < 1.782 for PLS and R2 > 0.973 and RMSEP < 0.486 for artificial neural networks (ANNs), respectively. Therefore, a combination of both an EIS-based technique and ANN models is suggested as a promising alternative to the traditional laboratory techniques for monitoring the pineapple waste saccharification step. PMID- 26861316 TI - Chemically Induced Reprogramming of Somatic Cells to Pluripotent Stem Cells and Neural Cells. AB - The ability to generate transplantable neural cells in a large quantity in the laboratory is a critical step in the field of developing stem cell regenerative medicine for neural repair. During the last few years, groundbreaking studies have shown that cell fate of adult somatic cells can be reprogrammed through lineage specific expression of transcription factors (TFs)-and defined culture conditions. This key concept has been used to identify a number of potent small molecules that could enhance the efficiency of reprogramming with TFs. Recently, a growing number of studies have shown that small molecules targeting specific epigenetic and signaling pathways can replace all of the reprogramming TFs. Here, we provide a detailed review of the studies reporting the generation of chemically induced pluripotent stem cells (ciPSCs), neural stem cells (ciNSCs), and neurons (ciN). We also discuss the main mechanisms of actions and the pathways that the small molecules regulate during chemical reprogramming. PMID- 26861318 TI - A Time-Domain Reflectometry Method with Variable Needle Pulse Width for Measuring the Dielectric Properties of Materials. AB - Time-domain reflectometry (TDR) methods used for measuring the dielectric properties of materials mostly utilize step or needle electrical pulses of constant amplitudes and shapes. Our novel approach enables determining the dielectric relaxation time of a sample using the analysis of the amplitudes of reflected pulses of two widths, in addition to bulk dielectric permittivity and electrical conductivity commonly obtained by the TDR technique. The method was developed for various values of electrical conductivity and relaxation time using numerical simulations of a five-rod probe placed in a material with complex dielectric permittivity described by the Debye model with an added electrical conductivity term. The characterization of amplitudes of two pulses of selected widths was done with regard to the dielectric parameters of simulated materials. The required probe parameters were obtained solely from numerical simulations. Verification was performed for the probe placed in aqueous KCl solutions with 14 different electrical conductivity values. The determined relaxation time remained roughly constant and independent of electrical conductivity. The obtained electrical conductivity agreed with the reference values. Our results indicate that the relaxation time, dielectric permittivity and electrical conductivity of the tested solutions can be simultaneously determined using a simple analysis of the amplitude and reflection time of two needle pulses of different widths. PMID- 26861319 TI - Recognition of Human Activities Using Continuous Autoencoders with Wearable Sensors. AB - This paper provides an approach for recognizing human activities with wearable sensors. The continuous autoencoder (CAE) as a novel stochastic neural network model is proposed which improves the ability of model continuous data. CAE adds Gaussian random units into the improved sigmoid activation function to extract the features of nonlinear data. In order to shorten the training time, we propose a new fast stochastic gradient descent (FSGD) algorithm to update the gradients of CAE. The reconstruction of a swiss-roll dataset experiment demonstrates that the CAE can fit continuous data better than the basic autoencoder, and the training time can be reduced by an FSGD algorithm. In the experiment of human activities' recognition, time and frequency domain feature extract (TFFE) method is raised to extract features from the original sensors' data. Then, the principal component analysis (PCA) method is applied to feature reduction. It can be noticed that the dimension of each data segment is reduced from 5625 to 42. The feature vectors extracted from original signals are used for the input of deep belief network (DBN), which is composed of multiple CAEs. The training results show that the correct differentiation rate of 99.3% has been achieved. Some contrast experiments like different sensors combinations, sensor units at different positions, and training time with different epochs are designed to validate our approach. PMID- 26861320 TI - Definition of an Enhanced Map-Matching Algorithm for Urban Environments with Poor GNSS Signal Quality. AB - Vehicle positioning is a key factor for numerous information and assistance applications that are included in vehicles and for which satellite positioning is mainly used. However, this positioning process can result in errors and lead to measurement uncertainties. These errors come mainly from two sources: errors and simplifications of digital maps and errors in locating the vehicle. From that inaccurate data, the task of assigning the vehicle's location to a link on the digital map at every instant is carried out by map-matching algorithms. These algorithms have been developed to fulfil that need and attempt to amend these errors to offer the user a suitable positioning. In this research; an algorithm is developed that attempts to solve the errors in positioning when the Global Navigation Satellite System (GNSS) signal reception is frequently lost. The algorithm has been tested with satisfactory results in a complex urban environment of narrow streets and tall buildings where errors and signal reception losses of the GPS receiver are frequent. PMID- 26861321 TI - A Survey on Intermediation Architectures for Underwater Robotics. AB - Currently, there is a plethora of solutions regarding interconnectivity and interoperability for networked robots so that they will fulfill their purposes in a coordinated manner. In addition to that, middleware architectures are becoming increasingly popular due to the advantages that they are capable of guaranteeing (hardware abstraction, information homogenization, easy access for the applications above, etc.). However, there are still scarce contributions regarding the global state of the art in intermediation architectures for underwater robotics. As far as the area of robotics is concerned, this is a major issue that must be tackled in order to get a holistic view of the existing proposals. This challenge is addressed in this paper by studying the most compelling pieces of work for this kind of software development in the current literature. The studied works have been assessed according to their most prominent features and capabilities. Furthermore, by studying the individual pieces of work and classifying them several common weaknesses have been revealed and are highlighted. This provides a starting ground for the development of a middleware architecture for underwater robotics capable of dealing with these issues. PMID- 26861322 TI - Using Finite Element and Eigenmode Expansion Methods to Investigate the Periodic and Spectral Characteristic of Superstructure Fiber Bragg Gratings. AB - In this study, a numerical simulation method was employed to investigate and analyze superstructure fiber Bragg gratings (SFBGs) with five duty cycles (50%, 33.33%, 14.28%, 12.5%, and 10%). This study focuses on demonstrating the relevance between design period and spectral characteristics of SFBGs (in the form of graphics) for SFBGs of all duty cycles. Compared with complicated and hard-to-learn conventional coupled-mode theory, the result of the present study may assist beginner and expert designers in understanding the basic application aspects, optical characteristics, and design techniques of SFBGs, thereby indirectly lowering the physical concepts and mathematical skills required for entering the design field. To effectively improve the accuracy of overall computational performance and numerical calculations and to shorten the gap between simulation results and actual production, this study integrated a perfectly matched layer (PML), perfectly reflecting boundary (PRB), object meshing method (OMM), and boundary meshing method (BMM) into the finite element method (FEM) and eigenmode expansion method (EEM). The integrated method enables designers to easily and flexibly design optical fiber communication systems that conform to the specific spectral characteristic by using the simulation data in this paper, which includes bandwidth, number of channels, and band gap size. PMID- 26861323 TI - Validity of the Kinect for Gait Assessment: A Focused Review. AB - Gait analysis may enhance clinical practice. However, its use is limited due to the need for expensive equipment which is not always available in clinical settings. Recent evidence suggests that Microsoft Kinect may provide a low cost gait analysis method. The purpose of this report is to critically evaluate the literature describing the concurrent validity of using the Kinect as a gait analysis instrument. An online search of PubMed, CINAHL, and ProQuest databases was performed. Included were studies in which walking was assessed with the Kinect and another gold standard device, and consisted of at least one numerical finding of spatiotemporal or kinematic measures. Our search identified 366 papers, from which 12 relevant studies were retrieved. The results demonstrate that the Kinect is valid only for some spatiotemporal gait parameters. Although the kinematic parameters measured by the Kinect followed the trend of the joint trajectories, they showed poor validity and large errors. In conclusion, the Kinect may have the potential to be used as a tool for measuring spatiotemporal aspects of gait, yet standardized methods should be established, and future examinations with both healthy subjects and clinical participants are required in order to integrate the Kinect as a clinical gait analysis tool. PMID- 26861324 TI - Active C4 Electrodes for Local Field Potential Recording Applications. AB - Extracellular neural recording, with multi-electrode arrays (MEAs), is a powerful method used to study neural function at the network level. However, in a high density array, it can be costly and time consuming to integrate the active circuit with the expensive electrodes. In this paper, we present a 4 mm * 4 mm neural recording integrated circuit (IC) chip, utilizing IBM C4 bumps as recording electrodes, which enable a seamless active chip and electrode integration. The IC chip was designed and fabricated in a 0.13 MUm BiCMOS process for both in vitro and in vivo applications. It has an input-referred noise of 4.6 MUV rms for the bandwidth of 10 Hz to 10 kHz and a power dissipation of 11.25 mW at 2.5 V, or 43.9 MUW per input channel. This prototype is scalable for implementing larger number and higher density electrode arrays. To validate the functionality of the chip, electrical testing results and acute in vivo recordings from a rat barrel cortex are presented. PMID- 26861325 TI - A Mobile Robot Localization via Indoor Fixed Remote Surveillance Cameras. AB - Localization, which is a technique required by service robots to operate indoors, has been studied in various ways. Most localization techniques have the robot measure environmental information to obtain location information; however, this is a high-cost option because it uses extensive equipment and complicates robot development. If an external device is used to determine a robot's location and transmit this information to the robot, the cost of internal equipment required for location recognition can be reduced. This will simplify robot development. Thus, this study presents an effective method to control robots by obtaining their location information using a map constructed by visual information from surveillance cameras installed indoors. With only a single image of an object, it is difficult to gauge its size due to occlusion. Therefore, we propose a localization method using several neighboring surveillance cameras. A two dimensional map containing robot and object position information is constructed using images of the cameras. The concept of this technique is based on modeling the four edges of the projected image of the field of coverage of the camera and an image processing algorithm of the finding object's center for enhancing the location estimation of objects of interest. We experimentally demonstrate the effectiveness of the proposed method by analyzing the resulting movement of a robot in response to the location information obtained from the two-dimensional map. The accuracy of the multi-camera setup was measured in advance. PMID- 26861326 TI - Investigation of Interference Models for RFID Systems. AB - The reader-to-reader collision in an RFID system is a challenging problem for communications technology. In order to model the interference between RFID readers, different interference models have been proposed, mainly based on two approaches: single and additive interference. The former only considers the interference from one reader within a certain range, whereas the latter takes into account the sum of all of the simultaneous interferences in order to emulate a more realistic behavior. Although the difference between the two approaches has been theoretically analyzed in previous research, their effects on the estimated performance of the reader-to-reader anti-collision protocols have not yet been investigated. In this paper, the influence of the interference model on the anti collision protocols is studied by simulating a representative state-of-the-art protocol. The results presented in this paper highlight that the use of additive models, although more computationally intensive, is mandatory to improve the performance of anti-collision protocols. PMID- 26861327 TI - Evaluating Quantum Dot Performance in Homogeneous FRET Immunoassays for Prostate Specific Antigen. AB - The integration of semiconductor quantum dots (QDs) into homogeneous Forster resonance energy transfer (FRET) immunoassay kits for clinical diagnostics can provide significant advantages concerning multiplexing and sensitivity. Here we present a facile and functional QD-antibody conjugation method using three commercially available QDs with different photoluminescence (PL) maxima (605 nm, 655 nm, and 705 nm). The QD-antibody conjugates were successfully applied for FRET immunoassays against prostate specific antigen (PSA) in 50 uL serum samples using Lumi4-Tb (Tb) antibody conjugates as FRET donors and time-gated PL detection on a KRYPTOR clinical plate reader. Forster distance and Tb donor background PL were directly related to the analytical sensitivity for PSA, which resulted in the lowest limits of detection for Tb-QD705 (2 nM), followed by Tb QD655 (4 nM), and Tb-QD605 (23 nM). Duplexed PSA detection using the Tb-QD655 and Tb-QD705 FRET-pairs demonstrated the multiplexing ability of our immunoassays. Our results show that FRET based on QD acceptors is suitable for multiplexed and sensitive biomarker detection in clinical diagnostics. PMID- 26861328 TI - A Complete Optical Sensor System Based on a POF-SPR Platform and a Thermo Stabilized Flow Cell for Biochemical Applications. AB - An optical sensor platform based on surface plasmon resonance (SPR) in a plastic optical fiber (POF) integrated into a thermo-stabilized flow cell for biochemical sensing applications is proposed. This device has been realized and experimentally tested by using a classic receptor-analyte assay. For this purpose, the gold surface of the POF was chemically modified through the formation of a self-assembling monolayer. The surface robustness of the POF-SPR platform has been tested for the first time thanks to the flow cell. The experimental results show that the proposed device can be successfully used for label-free biochemical sensing. The final goal of this work is to achieve a complete, small-size, simple to use and low cost optical sensor system. The whole system with the flow cell and the optical sensor are extensively described, together with the experimental results obtained with an immunoglobulin G (IgG)/anti-IgG assay. PMID- 26861329 TI - Mechanical Modulation of Phonon-Assisted Field Emission in a Silicon Nanomembrane Detector for Time-of-Flight Mass Spectrometry. AB - We demonstrate mechanical modulation of phonon-assisted field emission in a free standing silicon nanomembrane detector for time-of-flight mass spectrometry of proteins. The impacts of ion bombardment on the silicon nanomembrane have been explored in both mechanical and electrical points of view. Locally elevated lattice temperature in the silicon nanomembrane, resulting from the transduction of ion kinetic energy into thermal energy through the ion bombardment, induces not only phonon-assisted field emission but also a mechanical vibration in the silicon nanomembrane. The coupling of these mechanical and electrical phenomenon leads to mechanical modulation of phonon-assisted field emission. The thermal energy relaxation through mechanical vibration in addition to the lateral heat conduction and field emission in the silicon nanomembrane offers effective cooling of the nanomembrane, thereby allowing high resolution mass analysis. PMID- 26861330 TI - Post-Seismic Deformation from the 2009 Mw 6.3 Dachaidan Earthquake in the Northern Qaidam Basin Detected by Small Baseline Subset InSAR Technique. AB - On 28 August 2009, one thrust-faulting Mw 6.3 earthquake struck the northern Qaidam basin, China. Due to the lack of ground observations in this remote region, this study presents high-precision and high spatio-temporal resolution post-seismic deformation series with a small baseline subset InSAR technique. At the temporal scale, this changes from fast to slow with time, with a maximum uplift up to 7.4 cm along the line of sight 334 days after the event. At the spatial scale, this is more obvious at the hanging wall than that at the footwall, and decreases from the middle to both sides at the hanging wall. We then propose a method to calculate the correlation coefficient between co-seismic and post-seismic deformation by normalizing them. The correlation coefficient is found to be 0.73, indicating a similar subsurface process occurring during both phases. The results indicate that afterslip may dominate the post-seismic deformation during 19-334 days after the event, which mainly occurs with the fault geometry and depth similar to those of the c-seismic rupturing, and partly extends to the shallower and deeper depths. PMID- 26861331 TI - IEEE 802.15.4 ZigBee-Based Time-of-Arrival Estimation for Wireless Sensor Networks. AB - Precise time-of-arrival (TOA) estimation is one of the most important techniques in RF-based positioning systems that use wireless sensor networks (WSNs). Because the accuracy of TOA estimation is proportional to the RF signal bandwidth, using broad bandwidth is the most fundamental approach for achieving higher accuracy. Hence, ultra-wide-band (UWB) systems with a bandwidth of 500 MHz are commonly used. However, wireless systems with broad bandwidth suffer from the disadvantages of high complexity and high power consumption. Therefore, it is difficult to employ such systems in various WSN applications. In this paper, we present a precise time-of-arrival (TOA) estimation algorithm using an IEEE 802.15.4 ZigBee system with a narrow bandwidth of 2 MHz. In order to overcome the lack of bandwidth, the proposed algorithm estimates the fractional TOA within the sampling interval. Simulation results show that the proposed TOA estimation algorithm provides an accuracy of 0.5 m at a signal-to-noise ratio (SNR) of 8 dB and achieves an SNR gain of 5 dB as compared with the existing algorithm. In addition, experimental results indicate that the proposed algorithm provides accurate TOA estimation in a real indoor environment. PMID- 26861332 TI - Plastic Deformation of Micromachined Silicon Diaphragms with a Sealed Cavity at High Temperatures. AB - Single crystal silicon (SCS) diaphragms are widely used as pressure sensitive elements in micromachined pressure sensors. However, for harsh environments applications, pure silicon diaphragms are hardly used because of the deterioration of SCS in both electrical and mechanical properties. To survive at the elevated temperature, the silicon structures must work in combination with other advanced materials, such as silicon carbide (SiC) or silicon on insulator (SOI), for improved performance and reduced cost. Hence, in order to extend the operating temperatures of existing SCS microstructures, this work investigates the mechanical behavior of pressurized SCS diaphragms at high temperatures. A model was developed to predict the plastic deformation of SCS diaphragms and was verified by the experiments. The evolution of the deformation was obtained by studying the surface profiles at different anneal stages. The slow continuous deformation was considered as creep for the diaphragms with a radius of 2.5 mm at 600 degrees C. The occurrence of plastic deformation was successfully predicted by the model and was observed at the operating temperature of 800 degrees C and 900 degrees C, respectively. PMID- 26861333 TI - Vision-Based Pose Estimation for Robot-Mediated Hand Telerehabilitation. AB - Vision-based Pose Estimation (VPE) represents a non-invasive solution to allow a smooth and natural interaction between a human user and a robotic system, without requiring complex calibration procedures. Moreover, VPE interfaces are gaining momentum as they are highly intuitive, such that they can be used from untrained personnel (e.g., a generic caregiver) even in delicate tasks as rehabilitation exercises. In this paper, we present a novel master-slave setup for hand telerehabilitation with an intuitive and simple interface for remote control of a wearable hand exoskeleton, named HX. While performing rehabilitative exercises, the master unit evaluates the 3D position of a human operator's hand joints in real-time using only a RGB-D camera, and commands remotely the slave exoskeleton. Within the slave unit, the exoskeleton replicates hand movements and an external grip sensor records interaction forces, that are fed back to the operator therapist, allowing a direct real-time assessment of the rehabilitative task. Experimental data collected with an operator and six volunteers are provided to show the feasibility of the proposed system and its performances. The results demonstrate that, leveraging on our system, the operator was able to directly control volunteers' hands movements. PMID- 26861334 TI - An Improved STARFM with Help of an Unmixing-Based Method to Generate High Spatial and Temporal Resolution Remote Sensing Data in Complex Heterogeneous Regions. AB - Remote sensing technology plays an important role in monitoring rapid changes of the Earth's surface. However, sensors that can simultaneously provide satellite images with both high temporal and spatial resolution haven't been designed yet. This paper proposes an improved spatial and temporal adaptive reflectance fusion model (STARFM) with the help of an Unmixing-based method (USTARFM) to generate the high spatial and temporal data needed for the study of heterogeneous areas. The results showed that the USTARFM had higher accuracy than STARFM methods in two aspects of analysis: individual bands and of heterogeneity analysis. Taking the predicted NIR band as an example, the correlation coefficients (r) for the USTARFM, STARFM and unmixing methods were 0.96, 0.95, 0.90, respectively (p-value < 0.001); Root Mean Square Error (RMSE) values were 0.0245, 0.0300, 0.0401, respectively; and ERGAS values were 0.5416, 0.6507, 0.8737, respectively. The USTARM showed consistently higher performance than STARM when the degree of heterogeneity ranged from 2 to 10, highlighting that the use of this method provides the capacity to solve the data fusion problems faced when using STARFM. Additionally, the USTARFM method could help researchers achieve better performance than STARFM at a smaller window size from its heterogeneous land surface quantitative representation. PMID- 26861335 TI - Block Sparse Compressed Sensing of Electroencephalogram (EEG) Signals by Exploiting Linear and Non-Linear Dependencies. AB - This paper proposes a compressive sensing (CS) method for multi-channel electroencephalogram (EEG) signals in Wireless Body Area Network (WBAN) applications, where the battery life of sensors is limited. For the single EEG channel case, known as the single measurement vector (SMV) problem, the Block Sparse Bayesian Learning-BO (BSBL-BO) method has been shown to yield good results. This method exploits the block sparsity and the intra-correlation (i.e., the linear dependency) within the measurement vector of a single channel. For the multichannel case, known as the multi-measurement vector (MMV) problem, the Spatio-Temporal Sparse Bayesian Learning (STSBL-EM) method has been proposed. This method learns the joint correlation structure in the multichannel signals by whitening the model in the temporal and the spatial domains. Our proposed method represents the multi-channels signal data as a vector that is constructed in a specific way, so that it has a better block sparsity structure than the conventional representation obtained by stacking the measurement vectors of the different channels. To reconstruct the multichannel EEG signals, we modify the parameters of the BSBL-BO algorithm, so that it can exploit not only the linear but also the non-linear dependency structures in a vector. The modified BSBL-BO is then applied on the vector with the better sparsity structure. The proposed method is shown to significantly outperform existing SMV and also MMV methods. It also shows significant lower compression errors even at high compression ratios such as 10:1 on three different datasets. PMID- 26861337 TI - A Compressed Sensing-Based Wearable Sensor Network for Quantitative Assessment of Stroke Patients. AB - Clinical rehabilitation assessment is an important part of the therapy process because it is the premise for prescribing suitable rehabilitation interventions. However, the commonly used assessment scales have the following two drawbacks: (1) they are susceptible to subjective factors; (2) they only have several rating levels and are influenced by a ceiling effect, making it impossible to exactly detect any further improvement in the movement. Meanwhile, energy constraints are a primary design consideration in wearable sensor network systems since they are often battery-operated. Traditionally, for wearable sensor network systems that follow the Shannon/Nyquist sampling theorem, there are many data that need to be sampled and transmitted. This paper proposes a novel wearable sensor network system to monitor and quantitatively assess the upper limb motion function, based on compressed sensing technology. With the sparse representation model, less data is transmitted to the computer than with traditional systems. The experimental results show that the accelerometer signals of Bobath handshake and shoulder touch exercises can be compressed, and the length of the compressed signal is less than 1/3 of the raw signal length. More importantly, the reconstruction errors have no influence on the predictive accuracy of the Brunnstrom stage classification model. It also indicated that the proposed system can not only reduce the amount of data during the sampling and transmission processes, but also, the reconstructed accelerometer signals can be used for quantitative assessment without any loss of useful information. PMID- 26861336 TI - Development and Application of a Next Generation Air Sensor Network for the Hong Kong Marathon 2015 Air Quality Monitoring. AB - This study presents the development and evaluation of a next generation air monitoring system with both laboratory and field tests. A multi-parameter algorithm was used to correct for the impact of environmental conditions on the electrochemical sensors for carbon monoxide (CO) and nitrogen dioxide (NO2) pollutants. The field evaluation in an urban roadside environment in comparison to designated monitors showed good agreement with measurement error within 5% of the pollutant concentrations. Multiple sets of the developed system were then deployed in the Hong Kong Marathon 2015 forming a sensor-based network along the marathon route. Real-time air pollution concentration data were wirelessly transmitted and the Air Quality Health Index (AQHI) for the Green Marathon was calculated, which were broadcast to the public on an hourly basis. The route specific sensor network showed somewhat different pollutant patterns than routine air monitoring, indicating the immediate impact of traffic control during the marathon on the roadside air quality. The study is one of the first applications of a next generation sensor network in international sport events, and it demonstrated the usefulness of the emerging sensor-based air monitoring technology in rapid network deployment to supplement existing air monitoring. PMID- 26861338 TI - Spray Droplet Characterization from a Single Nozzle by High Speed Image Analysis Using an In-Focus Droplet Criterion. AB - Accurate spray characterization helps to better understand the pesticide spray application process. The goal of this research was to present the proof of principle of a droplet size and velocity measuring technique for different types of hydraulic spray nozzles using a high speed backlight image acquisition and analysis system. As only part of the drops of an agricultural spray can be in focus at any given moment, an in-focus criterion based on the gray level gradient was proposed to decide whether a given droplet is in focus or not. In a first experiment, differently sized droplets were generated with a piezoelectric generator and studied to establish the relationship between size and in-focus characteristics. In a second experiment, it was demonstrated that droplet sizes and velocities from a real sprayer could be measured reliably in a non-intrusive way using the newly developed image acquisition set-up and image processing. Measured droplet sizes ranged from 24 MUm to 543 MUm, depending on the nozzle type and size. Droplet velocities ranged from around 0.5 m/s to 12 m/s. The droplet size and velocity results were compared and related well with the results obtained with a Phase Doppler Particle Analyzer (PDPA). PMID- 26861339 TI - Poly(Ionic Liquid) Semi-Interpenetrating Network Multi-Responsive Hydrogels. AB - Herein we describe poly(ionic liquid) hydrogel actuators that are capable of responding to multiple stimuli, namely temperature, ionic strength and white light irradiation. Using two starting materials, a crosslinked poly ionic liquid (PIL) and a linear poly(N-isopropylacrylamide-co-spiropyran-co-acrylic acid), several semi-interpenetrating (sIPN) hydrogels were synthesised. The dimensions of hydrogels discs were measured before and after applying the stimuli, to quantify their response. Samples composed of 100% crosslinked PIL alone showed an average area reduction value of ~53% when the temperature was raised from 20 degrees C to 70 degrees C, ~24% when immersed in 1% w/w NaF salt solution and no observable photo-response. In comparison, sIPNs containing 300% w/w linear polymer showed an average area reduction of ~45% when the temperature was raised from 20 degrees C to 70 degrees C, ~36% when immersed in 1% NaF w/w salt solution and ~10% after 30 min exposure to white light irradiation, respectively. Moreover, by varying the content of the linear component, fine-control over the photo-, thermo- and salt response, swelling-deswelling rate and mechanical properties of the resulting sIPN was achieved. PMID- 26861340 TI - FingerScanner: Embedding a Fingerprint Scanner in a Raspberry Pi. AB - Nowadays, researchers are paying increasing attention to embedding systems. Cost reduction has lead to an increase in the number of platforms supporting the operating system Linux, jointly with the Raspberry Pi motherboard. Thus, embedding devices on Raspberry-Linux systems is a goal in order to make competitive commercial products. This paper presents a low-cost fingerprint recognition system embedded into a Raspberry Pi with Linux. PMID- 26861341 TI - Comparison of Thermal Detector Arrays for Off-Axis THz Holography and Real-Time THz Imaging. AB - In terahertz (THz) materials science, imaging by scanning prevails when low power THz sources are used. However, the application of array detectors operating with high power THz sources is increasingly reported. We compare the imaging properties of four different array detectors that are able to record THz radiation directly. Two micro-bolometer arrays are designed for infrared imaging in the 8-14 MUm wavelength range, but are based on different absorber materials (i) vanadium oxide; (ii) amorphous silicon; (iii) a micro-bolometer array optimized for recording THz radiation based on silicon nitride; and (iv) a pyroelectric array detector for THz beam profile measurements. THz wavelengths of 96.5 MUm, 118.8 MUm, and 393.6 MUm from a powerful far infrared laser were used to assess the technical performance in terms of signal to noise ratio, detector response and detectivity. The usefulness of the detectors for beam profiling and digital holography is assessed. Finally, the potential and limitation for real time digital holography are discussed. PMID- 26861342 TI - Efficient Donor Impurities in ZnO Nanorods by Polyethylene Glycol for Enhanced Optical and Glutamate Sensing Properties. AB - In this paper, we show that the possibility of using polyethylene glycol (EG) as a hydrogen source and it is used to assist the hydrothermal synthesis of ZnO nanorods (ZNRs). EG doping in ZNRs has been found to significantly improve their optical and chemical sensing characteristics toward glutamate. The EG was found to have no role on the structural properties of the ZNRs. However, the x-ray photoelectron spectroscopy (XPS) suggests that the EG could induce donor impurities effect in ZnO. Photoluminescence (PL) and UV-Vis. spectra demonstrated this doping effect. Mott-Schottky analysis at the ZNRs/electrolyte interface was used to investigate the charge density for the doped ZNRs and showed comparable dependence on the used amount of EG. Moreover, the doped ZNRs were used in potentiometric measurements for glutamate for a range from 10(-6) M to 10(-3) M and the potential response of the sensor electrode was linear with a slope of 91.15 mV/decade. The wide range and high sensitivity of the modified ZNRs based glutamate biosensor is attributed to the doping effect on the ZNRs that is dictated by the EG along with the high surface area-to-volume ratio. The findings in the present study suggest new avenues to control the growth of n-ZnO nanostructures and enhance the performance of their sensing devices. PMID- 26861343 TI - A Novel Piezoresistive Accelerometer with SPBs to Improve the Tradeoff between the Sensitivity and the Resonant Frequency. AB - For improving the tradeoff between the sensitivity and the resonant frequency of piezoresistive accelerometers, the dependency between the stress of the piezoresistor and the displacement of the structure is taken into consideration in this paper. In order to weaken the dependency, a novel structure with suspended piezoresistive beams (SPBs) is designed, and a theoretical model is established for calculating the location of SPBs, the stress of SPBs and the resonant frequency of the whole structure. Finite element method (FEM) simulations, comparative simulations and experiments are carried out to verify the good agreement with the theoretical model. It is demonstrated that increasing the sensitivity greatly without sacrificing the resonant frequency is possible in the piezoresistive accelerometer design. Therefore, the proposed structure with SPBs is potentially a novel option for improving the tradeoff between the sensitivity and the resonant frequency of piezoresistive accelerometers. PMID- 26861344 TI - Quartz-Enhanced Photoacoustic Spectroscopy with Right-Angle Prism. AB - A right-angle prism was used to enhance the acoustic signal of a quartz-enhanced photoacoustic spectroscopy (QEPAS) system. The incident laser beam was parallelly inverted by the right-angle prism and passed through the gap between two tuning fork prongs again to produce another acoustic excitation. Correspondingly, two pairs of rigid metal tubes were used as acoustic resonators with resonance enhancement factors of 16 and 12, respectively. The QEPAS signal was enhanced by a factor of 22.4 compared with the original signal, which was acquired without resonators or a prism. In addition, the system noise was reduced a little with double resonators due to the Q factor decrease. The signal-to-noise ratio (SNR) was greatly improved. Additionally, a normalized noise equivalent absorption coefficient (NNEA) of 5.8 * 10(-8) W.cm(-1).Hz(-1/2) was achieved for water vapor detection in the atmosphere. PMID- 26861345 TI - Industrial Internet of Things-Based Collaborative Sensing Intelligence: Framework and Research Challenges. AB - The development of an efficient and cost-effective solution to solve a complex problem (e.g., dynamic detection of toxic gases) is an important research issue in the industrial applications of the Internet of Things (IoT). An industrial intelligent ecosystem enables the collection of massive data from the various devices (e.g., sensor-embedded wireless devices) dynamically collaborating with humans. Effectively collaborative analytics based on the collected massive data from humans and devices is quite essential to improve the efficiency of industrial production/service. In this study, we propose a collaborative sensing intelligence (CSI) framework, combining collaborative intelligence and industrial sensing intelligence. The proposed CSI facilitates the cooperativity of analytics with integrating massive spatio-temporal data from different sources and time points. To deploy the CSI for achieving intelligent and efficient industrial production/service, the key challenges and open issues are discussed, as well. PMID- 26861347 TI - A Wearable Channel Selection-Based Brain-Computer Interface for Motor Imagery Detection. AB - Motor imagery-based brain-computer interface (BCI) is a communication interface between an external machine and the brain. Many kinds of spatial filters are used in BCIs to enhance the electroencephalography (EEG) features related to motor imagery. The approach of channel selection, developed to reserve meaningful EEG channels, is also an important technique for the development of BCIs. However, current BCI systems require a conventional EEG machine and EEG electrodes with conductive gel to acquire multi-channel EEG signals and then transmit these EEG signals to the back-end computer to perform the approach of channel selection. This reduces the convenience of use in daily life and increases the limitations of BCI applications. In order to improve the above issues, a novel wearable channel selection-based brain-computer interface is proposed. Here, retractable comb-shaped active dry electrodes are designed to measure the EEG signals on a hairy site, without conductive gel. By the design of analog CAR spatial filters and the firmware of EEG acquisition module, the function of spatial filters could be performed without any calculation, and channel selection could be performed in the front-end device to improve the practicability of detecting motor imagery in the wearable EEG device directly or in commercial mobile phones or tablets, which may have relatively low system specifications. Finally, the performance of the proposed BCI is investigated, and the experimental results show that the proposed system is a good wearable BCI system prototype. PMID- 26861346 TI - Application of 2D Non-Graphene Materials and 2D Oxide Nanostructures for Biosensing Technology. AB - The discovery of graphene and its unique properties has inspired researchers to try to invent other two-dimensional (2D) materials. After considerable research effort, a distinct "beyond graphene" domain has been established, comprising the library of non-graphene 2D materials. It is significant that some 2D non-graphene materials possess solid advantages over their predecessor, such as having a direct band gap, and therefore are highly promising for a number of applications. These applications are not limited to nano- and opto-electronics, but have a strong potential in biosensing technologies, as one example. However, since most of the 2D non-graphene materials have been newly discovered, most of the research efforts are concentrated on material synthesis and the investigation of the properties of the material. Applications of 2D non-graphene materials are still at the embryonic stage, and the integration of 2D non-graphene materials into devices is scarcely reported. However, in recent years, numerous reports have blossomed about 2D material-based biosensors, evidencing the growing potential of 2D non-graphene materials for biosensing applications. This review highlights the recent progress in research on the potential of using 2D non-graphene materials and similar oxide nanostructures for different types of biosensors (optical and electrochemical). A wide range of biological targets, such as glucose, dopamine, cortisol, DNA, IgG, bisphenol, ascorbic acid, cytochrome and estradiol, has been reported to be successfully detected by biosensors with transducers made of 2D non-graphene materials. PMID- 26861348 TI - A Localization Method for Underwater Wireless Sensor Networks Based on Mobility Prediction and Particle Swarm Optimization Algorithms. AB - Due to their special environment, Underwater Wireless Sensor Networks (UWSNs) are usually deployed over a large sea area and the nodes are usually floating. This results in a lower beacon node distribution density, a longer time for localization, and more energy consumption. Currently most of the localization algorithms in this field do not pay enough consideration on the mobility of the nodes. In this paper, by analyzing the mobility patterns of water near the seashore, a localization method for UWSNs based on a Mobility Prediction and a Particle Swarm Optimization algorithm (MP-PSO) is proposed. In this method, the range-based PSO algorithm is used to locate the beacon nodes, and their velocities can be calculated. The velocity of an unknown node is calculated by using the spatial correlation of underwater object's mobility, and then their locations can be predicted. The range-based PSO algorithm may cause considerable energy consumption and its computation complexity is a little bit high, nevertheless the number of beacon nodes is relatively smaller, so the calculation for the large number of unknown nodes is succinct, and this method can obviously decrease the energy consumption and time cost of localizing these mobile nodes. The simulation results indicate that this method has higher localization accuracy and better localization coverage rate compared with some other widely used localization methods in this field. PMID- 26861349 TI - Modeling of Rate-Dependent Hysteresis Using a GPO-Based Adaptive Filter. AB - A novel generalized play operator-based (GPO-based) nonlinear adaptive filter is proposed to model rate-dependent hysteresis nonlinearity for smart actuators. In the proposed filter, the input signal vector consists of the output of a tapped delay line. GPOs with various thresholds are used to construct a nonlinear network and connected with the input signals. The output signal of the filter is composed of a linear combination of signals from the output of GPOs. The least mean-square (LMS) algorithm is used to adjust the weights of the nonlinear filter. The modeling results of four adaptive filter methods are compared: GPO based adaptive filter, Volterra filter, backlash filter and linear adaptive filter. Moreover, a phenomenological operator-based model, the rate-dependent generalized Prandtl-Ishlinskii (RDGPI) model, is compared to the proposed adaptive filter. The various rate-dependent modeling methods are applied to model the rate-dependent hysteresis of a giant magnetostrictive actuator (GMA). It is shown from the modeling results that the GPO-based adaptive filter can describe the rate-dependent hysteresis nonlinear of the GMA more accurately and effectively. PMID- 26861350 TI - An ACOR-Based Multi-Objective WSN Deployment Example for Lunar Surveying. AB - Wireless sensor networks (WSNs) can gather in situ real data measurements and work unattended for long periods, even in remote, rough places. A critical aspect of WSN design is node placement, as this determines sensing capacities, network connectivity, network lifetime and, in short, the whole operational capabilities of the WSN. This paper proposes and studies a new node placement algorithm that focus on these aspects. As a motivating example, we consider a network designed to describe the distribution of helium-3 (3He), a potential enabling element for fusion reactors, on the Moon. 3He is abundant on the Moon's surface, and knowledge of its distribution is essential for future harvesting purposes. Previous data are inconclusive, and there is general agreement that on-site measurements, obtained over a long time period, are necessary to better understand the mechanisms involved in the distribution of this element on the Moon. Although a mission of this type is extremely complex, it allows us to illustrate the main challenges involved in a multi-objective WSN placement problem, i.e., selection of optimal observation sites and maximization of the lifetime of the network. To tackle optimization, we use a recent adaptation of the ant colony optimization (ACOR) metaheuristic, extended to continuous domains. Solutions are provided in the form of a Pareto frontier that shows the optimal equilibria. Moreover, we compared our scheme with the four-directional placement (FDP) heuristic, which was outperformed in all cases. PMID- 26861351 TI - Design and Analysis of a Single-Camera Omnistereo Sensor for Quadrotor Micro Aerial Vehicles (MAVs). AB - We describe the design and 3D sensing performance of an omnidirectional stereo (omnistereo) vision system applied to Micro Aerial Vehicles (MAVs). The proposed omnistereo sensor employs a monocular camera that is co-axially aligned with a pair of hyperboloidal mirrors (a vertically-folded catadioptric configuration). We show that this arrangement provides a compact solution for omnidirectional 3D perception while mounted on top of propeller-based MAVs (not capable of large payloads). The theoretical single viewpoint (SVP) constraint helps us derive analytical solutions for the sensor's projective geometry and generate SVP compliant panoramic images to compute 3D information from stereo correspondences (in a truly synchronous fashion). We perform an extensive analysis on various system characteristics such as its size, catadioptric spatial resolution, field of-view. In addition, we pose a probabilistic model for the uncertainty estimation of 3D information from triangulation of back-projected rays. We validate the projection error of the design using both synthetic and real-life images against ground-truth data. Qualitatively, we show 3D point clouds (dense and sparse) resulting out of a single image captured from a real-life experiment. We expect the reproducibility of our sensor as its model parameters can be optimized to satisfy other catadioptric-based omnistereo vision under different circumstances. PMID- 26861352 TI - Evaluation of the Effects of Hidden Node Problems in IEEE 802.15.7 Uplink Performance. AB - In the last few years, the increasing use of LEDs in illumination systems has been conducted due to the emergence of Visible Light Communication (VLC) technologies, in which data communication is performed by transmitting through the visible band of the electromagnetic spectrum. In 2011, the Institute of Electrical and Electronics Engineers (IEEE) published the IEEE 802.15.7 standard for Wireless Personal Area Networks based on VLC. Due to limitations in the coverage of the transmitted signal, wireless networks can suffer from the hidden node problems, when there are nodes in the network whose transmissions are not detected by other nodes. This problem can cause an important degradation in communications when they are made by means of the Carrier Sense Multiple Access with Collision Avoidance (CSMA/CA) access control method, which is used in IEEE 802.15.7 This research work evaluates the effects of the hidden node problem in the performance of the IEEE 802.15.7 standard We implement a simulator and analyze VLC performance in terms of parameters like end-to-end goodput and message loss rate. As part of this research work, a solution to the hidden node problem is proposed, based on the use of idle patterns defined in the standard. Idle patterns are sent by the network coordinator node to communicate to the other nodes that there is an ongoing transmission. The validity of the proposed solution is demonstrated with simulation results. PMID- 26861353 TI - Biomolecules and Natural Medicine Preparations: Analysis of New Sources of Bioactive Compounds from Ribes and Rubus spp. Buds. AB - It is well known that plants are important sources for the preparation of natural remedies as they contain many biologically active compounds. In particular, polyphenols, terpenic compounds, organic acids, and vitamins are the most widely occurring groups of phytochemicals. Some endemic species may be used for the production of herbal preparations containing phytochemicals with significant bioactivity, as antioxidant activity and anti-inflammatory capacities, and health benefits. Blackberry sprouts and blackcurrant buds are known to contain appreciable levels of bioactive compounds, including flavonols, phenolic acids, monoterpenes, vitamin C, and catechins, with several clinical effects. The aim of this research was to perform an analytical study of blackcurrant and blackberry bud-preparations, in order to identify and quantify the main biomarkers, obtaining a specific phytochemical fingerprint to evaluate the single botanical class contribution to total phytocomplex and relative bioactivity, using a High Performance Liquid Chromatograph-Diode Array Detector; the same analyses were performed both on the University laboratory and commercial preparations. Different chromatographic methods were used to determine concentrations of biomolecules in the preparations, allowing for quantification of statistically significant differences in their bioactive compound content both in the case of Ribes nigrum and Rubus cultivated varieties at different harvest stages. In blackcurrant bud-extracts the most important class was organic acids (50.98%) followed by monoterpenes (14.05%), while in blackberry preparations the main bioactive classes were catechins (50.06%) and organic acids (27.34%). Chemical, pharmaceutical and agronomic-environmental knowledge could be important for obtaining label certifications for the valorization of specific genotypes, with high clinical and pharmaceutical value: this study allowed to develop an effective tool for the natural preparation quality control and bioactivity evaluation through the chemical fingerprinting of bud preparations. PMID- 26861354 TI - Propofol and AZD3043 Inhibit Adult Muscle and Neuronal Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes. AB - Propofol is a widely used general anaesthetic with muscle relaxant properties. Similarly as propofol, the new general anaesthetic AZD3043 targets the GABAA receptor for its anaesthetic effects, but the interaction with nicotinic acetylcholine receptors (nAChRs) has not been investigated. Notably, there is a gap of knowledge about the interaction between propofol and the nAChRs found in the adult neuromuscular junction. The objective was to evaluate whether propofol or AZD3043 interact with the alpha1beta1deltaepsilon, alpha3beta2, or alpha7 nAChR subtypes that can be found in the neuromuscular junction and if there are any differences in affinity for those subtypes between propofol and AZD3043. Human nAChR subtypes alpha1beta1deltaepsilon, alpha3beta2, and alpha7 were expressed into Xenopus oocytes and studied with an automated voltage-clamp. Propofol and AZD3043 inhibited ACh-induced currents in all of the nAChRs studied with inhibitory concentrations higher than those needed for general anaesthesia. AZD3043 was a more potent inhibitor at the adult muscle nAChR subtype compared to propofol. Propofol and AZD3043 inhibit nAChR subtypes that can be found in the adult NMJ in concentrations higher than needed for general anaesthesia. This finding needs to be evaluated in an in vitro nerve-muscle preparation and suggests one possible explanation for the muscle relaxant effect of propofol seen during higher doses. PMID- 26861355 TI - Alkaloids from the Sponge Stylissa carteri Present Prospective Scaffolds for the Inhibition of Human Immunodeficiency Virus 1 (HIV-1). AB - The sponge Stylissa carteri is known to produce a number of secondary metabolites displaying anti-fouling, anti-inflammatory, and anti-cancer activity. However, the anti-viral potential of metabolites produced by S. carteri has not been extensively explored. In this study, an S. carteri extract was HPLC fractionated and a cell based assay was used to evaluate the effects of HPLC fractions on parameters of Human Immunodeficiency Virus (HIV-1) infection and cell viability. Candidate HIV-1 inhibitory fractions were then analyzed for the presence of potential HIV-1 inhibitory compounds by mass spectrometry, leading to the identification of three previously characterized compounds, i.e., debromohymenialdisine (DBH), hymenialdisine (HD), and oroidin. Commercially available purified versions of these molecules were re-tested to assess their antiviral potential in greater detail. Specifically, DBH and HD exhibit a 30%-40% inhibition of HIV-1 at 3.1 MUM and 13 MUM, respectively; however, both exhibited cytotoxicity. Conversely, oroidin displayed a 50% inhibition of viral replication at 50 MUM with no associated toxicity. Additional experimentation using a biochemical assay revealed that oroidin inhibited the activity of the HIV-1 Reverse Transcriptase up to 90% at 25 MUM. Taken together, the chemical search space was narrowed and previously isolated compounds with an unexplored anti viral potential were found. Our results support exploration of marine natural products for anti-viral drug discovery. PMID- 26861357 TI - Angiotensin I Converting Enzyme Inhibitory Peptides Derived from Phycobiliproteins of Dulse Palmaria palmata. AB - We examined the inhibitory activity of angiotensin I converting enzyme (ACE) in protein hydrolysates from dulse, Palmaria palmata. The proteins extracted from dulse were mainly composed of phycoerythrin (PE) followed by phycocyanin (PC) and allophycocyanin (APC). The dulse proteins showed slight ACE inhibitory activity, whereas the inhibitory activity was extremely enhanced by thermolysin hydrolysis. The ACE inhibitory activity of hydrolysates was hardly affected by additional pepsin, trypsin and chymotrypsin treatments. Nine ACE inhibitory peptides (YRD, AGGEY, VYRT, VDHY, IKGHY, LKNPG, LDY, LRY, FEQDWAS) were isolated from the hydrolysates by reversed-phase high-performance liquid chromatography (HPLC), and it was demonstrated that the synthetic peptide LRY (IC50: 0.044 MUmol) has remarkably high ACE inhibitory activity. Then, we investigated the structural properties of dulse phycobiliproteins to discuss the origin of dulse ACE inhibitory peptides. Each dulse phycobiliprotein possesses alpha-subunit (Mw: 17,477-17,638) and beta-subunit (Mw: 17,455-18,407). The sequences of YRD, AGGEY, VYRT, VDHY, LKNPG and LDY were detected in the primary structure of PE alpha subunit, and the LDY also exists in the APC alpha- and beta-subunits. In addition, the LRY sequence was found in the beta-subunits of PE, PC and APC. From these results, it was suggested that the dulse ACE inhibitory peptides were derived from phycobiliproteins, especially PE. To make sure the deduction, we carried out additional experiment by using recombinant PE. We expressed the recombinant alpha- and beta-subunits of PE (rPEalpha and rPEbeta, respectively), and then prepared their peptides by thermolysin hydrolysis. As a result, these peptides showed high ACE inhibitory activities (rPEalpha: 94.4%; rPEbeta: 87.0%). Therefore, we concluded that the original proteins of dulse ACE inhibitory peptides were phycobiliproteins. PMID- 26861356 TI - Palytoxin-Containing Aquarium Soft Corals as an Emerging Sanitary Problem. AB - Palytoxin (PLTX), one the most potent marine toxins, and/or its analogs, have been identified in different marine organisms, such as Palythoa soft corals, Ostreopsis dinoflagellates, and Trichodesmium cyanobacteria. Although the main concern for human health is PLTXs entrance in the human food chain, there is growing evidence of adverse effects associated with inhalational, cutaneous, and/or ocular exposure to aquarium soft corals contaminated by PLTXs or aquaria waters. Indeed, the number of case reports describing human poisonings after handling these cnidarians is continuously increasing. In general, the signs and symptoms involve mainly the respiratory (rhinorrhea and coughing), skeletomuscular (myalgia, weakness, spasms), cardiovascular (electrocardiogram alterations), gastrointestinal (nausea), and nervous (paresthesia, ataxia, tremors) systems or apparates. The widespread phenomenon, the entity of the signs and symptoms of poisoning and the lack of control in the trade of corals as aquaria decorative elements led to consider these poisonings an emerging sanitary problem. This review summarizes literature data on human poisonings due to, or ascribed to, PLTX-containing soft corals, focusing on the different PLTX congeners identified in these organisms and their toxic potential. PMID- 26861360 TI - Environment and Its Influence on Health and Demographics in South Korea. AB - As the prevalence of overweight and obesity has been increasing in South Korea, it is critical to better understand possible associations between environmental surroundings and general health status. We characterize key health test readings and basic demographic information from 10,816 South Koreans, obtained from two Ubiquitous Healthcare (U-Healthcare) centers that have distinct surrounding neighborhood characteristics. One is located in a rural area in Busan, the other is located in an urban area in Daegu surrounded by a highly crowded residential and commercial business area. We analyze comprehensive health data sets, including blood pressure, body mass index, pulse rate, and body fat percentage from December 2013 to December 2014 to study differences in overall health test measurements between users of rural and urban U-Healthcare centers. We conduct multiple regression analyses to evaluate differences in general health status between the two centers, adjusting for confounding factors. We report statistical evidence of differences in blood pressure at the two locations. As local residents are major users, the result indicates that the environmental surroundings of the centers can influence the demographics of the users, the type of health tests in demand, and the users' health status. We further envision that U-Healthcare centers will provide public users with an opportunity for enhancing their current health, which could potentially be used to prevent them from developing chronic diseases, while providing surveillance healthcare data. PMID- 26861358 TI - Marine Origin Polysaccharides in Drug Delivery Systems. AB - Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine. PMID- 26861359 TI - Potential Anti-Atherosclerotic Properties of Astaxanthin. AB - Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed. PMID- 26861361 TI - Evaluation of Microbiological and Chemical Contaminants in Poultry Farms. AB - The aim of the study was to evaluate the microbiological and chemical contamination in settled dust at poultry farms. The scope of research included evaluating the contributions of the various granulometric fractions in settled dust samples, assessing microbial contamination using culture methods, concentrations of secondary metabolites in dust and their cytotoxicity against hepatocyte chicken cells by means of MTT (3-(4,5-dimethylthiazolyl-2)-2,5 diphenyltetrazolium bromide) tests. In addition, we also evaluated the concentration of selected volatile odorous compounds (VOCs) using gas chromatographic and spectrophotometric methods and airborne dust concentration in the air with DustTrakTM DRX Aerosol Monitor. Studies were carried out on chicken broilers and laying hens at 13 poultry farms, with numbers of birds ranging from 8000 to 42,000. The airborne total dust concentration at poultry farms averaged 1.44 mg/m3 with a high percentage of the PM10 fraction (particulate matter with a diameter less than 10 MUm). Microorganism concentrations in the settled dust were: 3.2 * 108 cfu/g for bacteria and 1.2 * 106 cfu/g for fungi. Potential pathogens (Enterococcus spp., Escherichia coli, Salmonella spp., Aspergillus fumigatus, Paecilomyces variotii) were also found. Secondary metabolites included aurofusarin, deoxynivalenol, 15-hydroxyculmorin zearalenone, zearalenone-sulfate, infectopyron, and neochinulin A. However, the dust samples showed weak cytotoxicity towards chicken hepatocyte cells, which ranged between 9.2% and 29.7%. Among volatile odorous compounds ammonia, acrolein, methyloamine, acetic acid, acetoaldehyde and formaldehyde were detected in the air. In conclusion, settled dust can be a carrier of microorganisms, odours and secondary metabolites in poultry farms, which can be harmful to workers' health. PMID- 26861362 TI - The Impact of Knowledge of Suicide Prevention and Work Experience among Clinical Staff on Attitudes towards Working with Suicidal Patients and Suicide Prevention. AB - Suicide-preventive training has shown to influence attitudes. This study aimed at investigating what impact other factors than knowledge might have on attitudes towards work with suicidal patients and suicide prevention. In 2007, 500 health care staff working in a psychiatric clinic in Stockholm received a questionnaire with items concerning work with suicidal patients to which 358 (71.6%) responded. A set of attitude items were tested using structural equation modelling (LISREL). Three models were found to be satisfactory valid and reliable: Job clarity, Job confidence and Attitudes towards prevention. These were then used in regression analyses as dependent variables with predictors such as experience of work with suicidal patients, perceived sufficient training, age and gender. Perceived sufficient training was consistently the most important predictor for all three attitude concepts (p < 0.01, beta = 0.559 for Job clarity; p < 0.01, beta = 0.53 for Job confidence; p < 0.01, beta = 0.191 for Attitudes towards prevention). Age was another significant predictor for Job clarity (p < 0.05, beta = 0.134), as was experience of patient suicide for Job confidence (p < 0.05, beta = 0.137). It is concluded that providing suicide preventive education is likely to improve attitudes towards the prevention of suicide, clarity and confidence regarding their role in the care for suicidal patients. These improvements may contribute to the prevention of suicide in health care settings. PMID- 26861363 TI - Simultaneous Detection of Five Pathogens from Cerebrospinal Fluid Specimens Using Luminex Technology. AB - Early diagnosis and treatment are crucial for the outcome of central nervous system (CNS) infections. In this study, we developed a multiplex PCR-Luminex assay for the simultaneous detection of five major pathogens, including Mycobacterium tuberculosis, Cryptococcus neoformans, Streptococcus pneumoniae, and herpes simplex virus types 1 and 2, which frequently cause CNS infections. Through the hybridization reaction between multiplex PCR-amplified targets and oligonucleotide "anti-TAG" sequences, we found that the PCR-Luminex assay could detect as low as 101-102 copies of synthetic pathogen DNAs. Furthermore, 163 cerebrospinal fluid (CSF) specimens from patients with suspected CNS infections were used to evaluate the efficiency of this multiplex PCR-Luminex method. Compared with Ziehl-Neelsen stain, this assay showed a high diagnostic accuracy for tuberculosis meningitis (sensitivity, 90.7% and specificity, 99.1%). For cryptococcal meningitis, the sensitivity and specificity were 92% and 97.1%, respectively, compared with the May Grunwald Giemsa (MGG) stain. For herpes simplex virus types 1 and 2 encephalitis, the sensitivities were 80.8% and 100%, and the specificities were 94.2% and 99%, respectively, compared with Enzyme Linked Immunosorbent Assay (ELISA) assays. Taken together, this multiplex PCR Luminex assay showed potential efficiency for the simultaneous detection of five pathogens and may be a promising supplement to conventional methods for diagnosing CNS infections. PMID- 26861364 TI - Prevalence of Residential Dampness and Mold Exposure in a University Student Population. AB - The impact of residential dampness or mold on respiratory health is well established but few studies have focused on university students. This study aims to: (a) describe the prevalence of exposure to residential dampness or mold in university students according to socio-geographic factors and (b) identify associated housing characteristics. A web survey was conducted in 2014 among the 26,676 students registered at the Universite de Sherbrooke (QC, Canada). Residential dampness and mold being closely intertwined, they were considered as a single exposure and assessed using a validated questionnaire. Exposure was compared according to socio-geographic and housing characteristics using chi square tests and logistic regressions. Among the 2097 participants included in the study (response rate: 8.1%), over 80% were tenants. Residential exposure to dampness or mold was frequent (36.0%, 95% CI: 33.9-38.1). Marked differences for this exposure were noted according to home ownership (39.7% vs. 25.5% among tenants and owners respectively; OR = 1.92%, 95% CI: 1.54-2.38). Campus affiliation, household composition and the number of residents per building were associated with exposure to dampness or mold (p < 0.01), while sex and age were not. Exposure was also associated with older buildings, and buildings in need of renovations and lacking proper ventilation (p < 0.001). This study highlights the potential risk of university students suffering from mold-related health effects given their frequent exposure to this agent. Further research is needed to fully evaluate the mold-related health impact in this at risk group. PMID- 26861365 TI - Advancing Sustainability through Urban Green Space: Cultural Ecosystem Services, Equity, and Social Determinants of Health. AB - Urban green spaces provide an array of benefits, or ecosystem services, that support our physical, psychological, and social health. In many cases, however, these benefits are not equitably distributed across diverse urban populations. In this paper, we explore relationships between cultural ecosystem services provided by urban green space and the social determinants of health outlined in the United States Healthy People 2020 initiative. Specifically, we: (1) explore connections between cultural ecosystem services and social determinants of health; (2) examine cultural ecosystem services as nature-based health amenities to promote social equity; and (3) recommend areas for future research examining links between urban green space and public health within the context of environmental justice. PMID- 26861366 TI - Health Impact Assessment for Second-Hand Smoke Exposure in Germany--Quantifying Estimates for Ischaemic Heart Diseases, COPD, and Stroke. AB - Evidence of the adverse health effects attributable to second-hand smoke (SHS) exposure is available. This study aims to quantify the impact of SHS exposure on ischaemic heart diseases (IHD), chronic obstructive pulmonary diseases (COPD), and stroke in Germany. Therefore, this study estimated and forecasted the morbidity for the three outcomes in the German population. Furthermore, a health impact assessment was performed using DYNAMO-HIA, which is a generic software tool applying a Markov model. Overall 687,254 IHD cases, 231,973 COPD cases, and 288,015 stroke cases were estimated to be attributable to SHS exposure in Germany for 2014. Under the assumption that the population prevalence of these diseases and the prevalence of SHS exposure remain constant, the total number of cases will increase due to demographic aging. Assuming a total eradication of SHS exposure beginning in 2014 leads to an estimated reduction of 50% in cases, compared to the reference scenario in 2040 for all three diseases. The results highlight the relevance of SHS exposure because it affects several chronic disease conditions and has a major impact on the population's health. Therefore, public health campaigns to protect non-smokers are urgently needed. PMID- 26861367 TI - Virulence Factors and Antibiotic Susceptibility of Staphylococcus aureus Isolates in Ready-to-Eat Foods: Detection of S. aureus Contamination and a High Prevalence of Virulence Genes. AB - Staphylococcus aureus is one of the leading causes of food poisoning. Its pathogenicity results from the possession of virulence genes that produce different toxins which result in self-limiting to severe illness often requiring hospitalization. In this study of 200 sushi and sashimi samples, S. aureus contamination was confirmed in 26% of the food samples. The S. aureus isolates were further characterized for virulence genes and antibiotic susceptibility. A high incidence of virulence genes was identified in 96.2% of the isolates and 20 different virulence gene profiles were confirmed. DNA amplification showed that 30.8% (16/52) of the S. aureus carried at least one SE gene which causes staphylococcal food poisoning. The most common enterotoxin gene was seg (11.5%) and the egc cluster was detected in 5.8% of the isolates. A combination of hla and hld was the most prevalent coexistence virulence genes and accounted for 59.6% of all isolates. Antibiotic resistance studies showed tetracycline resistance to be the most common at 28.8% while multi-drug resistance was found to be low at 3.8%. In conclusion, the high rate of S. aureus in the sampled sushi and sashimi indicates the need for food safety guidelines. PMID- 26861369 TI - Evaluation of an Early-Warning System for Heat Wave-Related Mortality in Europe: Implications for Sub-seasonal to Seasonal Forecasting and Climate Services. AB - Heat waves have been responsible for more fatalities in Europe over the past decades than any other extreme weather event. However, temperature-related illnesses and deaths are largely preventable. Reliable sub-seasonal-to-seasonal (S2S) climate forecasts of extreme temperatures could allow for better short-to medium-term resource management within heat-health action plans, to protect vulnerable populations and ensure access to preventive measures well in advance. The objective of this study is to assess the extent to which S2S climate forecasts could be incorporated into heat-health action plans, to support timely public health decision-making ahead of imminent heat wave events in Europe. Forecasts of apparent temperature at different lead times (e.g., 1 day, 4 days, 8 days, up to 3 months) were used in a mortality model to produce probabilistic mortality forecasts up to several months ahead of the 2003 heat wave event in Europe. Results were compared to mortality predictions, inferred using observed apparent temperature data in the mortality model. In general, we found a decreasing transition in skill between excellent predictions when using observed temperature, to predictions with no skill when using forecast temperature with lead times greater than one week. However, even at lead-times up to three months, there were some regions in Spain and the United Kingdom where excess mortality was detected with some certainty. This suggests that in some areas of Europe, there is potential for S2S climate forecasts to be incorporated in localised heat health action plans. In general, these results show that the performance of this climate service framework is not limited by the mortality model itself, but rather by the predictability of the climate variables, at S2S time scales, over Europe. PMID- 26861368 TI - Modified Ideal Cardiovascular Health Status is Associated with Lower Prevalence of Stroke in Rural Northeast China. AB - BACKGROUND: In 2010, the American Heart Association developed a new definition of ideal cardiovascular health (CVH) based on seven cardiovascular health metrics. This study aimed to investigate the relationship between modified ideal CVH metrics and the risk of stroke in the rural population of Northeast China. METHODS: We included 11,417 adults from the rural population in Northeast China and collected all the information, including the baseline characteristics, history of stroke, and the seven ideal CVH metrics. RESULTS: Our results showed that the presence of stroke was associated with high body mass index (BMI), poor diet score (salt intake), high total cholesterol (TC), high blood pressure (BP), and high fasting plasma glucose (FPG). The prevalence of stroke increased as the number of ideal CVH metrics decreased, and peaked to 13.1% among those with only one ideal CVH metric. Participants with only one ideal CVH had a 4.40-fold increased susceptibility of stroke than those with all seven ideal health metrics. CONCLUSION: This study revealed that people with a better CVH status had a lower prevalence of stroke and the susceptibility of stroke increased with the decreasing of the number of ideal CVH metrics. PMID- 26861370 TI - Experimental Assessment of Recycled Diesel Spill-Contaminated Domestic Wastewater Treated by Reed Beds for Irrigation of Sweet Peppers. AB - The aim of this experimental study is to assess if urban wastewater treated by ten different greenhouse-based sustainable wetland systems can be recycled to irrigate Capsicum annuum L. (Sweet Pepper; California Wonder) commercially grown either in compost or sand within a laboratory environment. The design variables were aggregate diameter, contact time, resting time and chemical oxygen demand. The key objectives were to assess: (i) the suitability of different treated (recycled) wastewaters for irrigation; (ii) response of peppers in terms of growth when using recycled wastewater subject to different growth media and hydrocarbon contamination; and (iii) the economic viability of different experimental set-ups in terms of marketable yield. Ortho-phosphate-phosphorus, ammonia-nitrogen, potassium and manganese concentrations in the irrigation water considerably exceeded the corresponding water quality thresholds. A high yield in terms of economic return (marketable yield expressed in monetary value) was linked to raw wastewater and an organic growth medium, while the plants grown in organic medium and wetlands of large aggregate size, high contact and resting times, diesel-spill contamination and low inflow loading rate produced the best fruits in terms of their dimensions and fresh weights, indicating the role of diesel in reducing too high nitrogen concentrations. PMID- 26861371 TI - Legacies of Lead in Charm City's Soil: Lessons from the Baltimore Ecosystem Study. AB - Understanding the spatial distribution of soil lead has been a focus of the Baltimore Ecosystem Study since its inception in 1997. Through multiple research projects that span spatial scales and use different methodologies, three overarching patterns have been identified: (1) soil lead concentrations often exceed state and federal regulatory limits; (2) the variability of soil lead concentrations is high; and (3) despite multiple sources and the highly heterogeneous and patchy nature of soil lead, discernable patterns do exist. Specifically, housing age, the distance to built structures, and the distance to a major roadway are strong predictors of soil lead concentrations. Understanding what drives the spatial distribution of soil lead can inform the transition of underutilized urban space into gardens and other desirable land uses while protecting human health. A framework for management is proposed that considers three factors: (1) the level of contamination; (2) the desired land use; and (3) the community's preference in implementing the desired land use. The goal of the framework is to promote dialogue and resultant policy changes that support consistent and clear regulatory guidelines for soil lead, without which urban communities will continue to be subject to the potential for lead exposure. PMID- 26861372 TI - Flood-Exposure is Associated with Higher Prevalence of Child Undernutrition in Rural Eastern India. AB - BACKGROUND: Child undernutrition and flooding are highly prevalent public health issues in Asia, yet epidemiological studies investigating this association are lacking. METHODS: To investigate to what extent floods exacerbate poor nutritional status in children and identify most vulnerable groups, we conducted a population-based survey of children aged 6-59 months inhabiting flooded and non flooded communities of the Jagatsinghpur district, Odisha (India), one year after large floods in 2008. Anthropometric measurements on 879 children and child, parental and household level variables were collected through face-to-face interviews in September 2009. The association between flooding and the prevalence of wasting, stunting and underweight was examined using weighted multivariate logistic regression for children inhabiting communities exposed solely to floods in 2008 and those communities repeatedly flooded (2006 and 2008) controlling for parental education and other relevant variables. We examined the influence of age on this association. Propensity score matching was conducted to test the robustness of our findings. RESULTS: The prevalence of wasting among children flooded in 2006 and 2008 was 51.6%, 41.4% in those flooded only in 2008, and 21.2% in children inhabiting non-flooded communities. Adjusting by confounders, the increased prevalence relative to non-flooded children in the exposed groups were 2.30 (adjusted prevalence ratio (aPR); 95% CI: 1.86, 2.85) and 1.94 (95% CI: 1.43, 2.63), respectively. Among repeatedly flooded communities, cases of severe wasting in children were 3.37 times more prevalent than for children inhabiting in those non-flooded (95% CI: 2.34, 4.86) and nearly twice more prevalent relative to those flooded only once. Those children younger than one year during previous floods in 2006 showed the largest difference in prevalence of wasting compared to their non-flooded counterparts (aPR: 4.01; 95% CI: 1.51, 10.63). RESULTS were robust to alternative adjusted models and in propensity score matching analyses. For similar analyses, no significant associations were found for child stunting, and more moderate effects were observed in the case of child underweight. CONCLUSIONS: Particularly in low-resource or subsistence-farming rural settings, long-lasting nutritional response in the aftermath of floods should be seriously considered to counteract the long-term nutritional effects on children, particularly infants, and include their mothers on whom they are dependent. The systematic monitoring of nutritional status in these groups might help to tailor efficient responses in each particular context. PMID- 26861373 TI - Cultural and Molecular Evidence of Legionella spp. Colonization in Dental Unit Waterlines: Which Is the Best Method for Risk Assessment? AB - Legionella spp. are ubiquitous in aquatic habitats and water distribution systems, including dental unit waterlines (DUWLs). The aim of the present study was to determine the prevalence of Legionella in DUWLs and tap water samples using PMA-qPCR and standard culture methods. The total viable counts (TVCs) of aerobic heterotrophic bacteria in the samples were also determined. Legionella spp. were detected and quantified using the modified ISO 11731 culture method. Extracted genomic DNA was analysed using the iQ-Check Quanti Legionella spp. kit, and the TVCs were determined according to the ISO protocol 6222. Legionella spp. were detected in 100% of the samples using the PMA-qPCR method, whereas these bacteria were detected in only 7% of the samples using the culture method. The number of colony forming units (CFUs) of the TVCs in the DUWL and tap water samples differed, with the bacterial load being significantly lower in the tap water samples (p-value = 0). The counts obtained were within the Italian standard range established for potable water in only 5% of the DUWL water samples and in 77% of the tap water samples. Our results show that the level of Legionella spp. contamination determined using the culture method does not reflect the true scale of the problem, and consequently we recommend testing for the presence of aerobic heterotrophic bacteria based on the assumption that Legionella spp. are components of biofilms. PMID- 26861374 TI - The Impact of Physical and Ergonomic Hazards on Poultry Abattoir Processing Workers: A Review. AB - The poultry abattoir industry continues to grow and contribute significantly to the gross domestic product in many countries. The industry expects working shifts of eight to eleven hours, during which workers are exposed to occupational hazards which include physical hazards ranging from noise, vibration, exposure to cold and ergonomic stress from manual, repetitive tasks that require force. A PubMed, Medline and Science Direct online database search, using specific keywords was conducted and the results confirmed that physical and ergonomic hazards impact on abattoir processing workers health, with harm not only to workers' health but also as an economic burden due to the loss of their livelihoods and the need for treatment and compensation in the industry. This review endeavours to highlight the contribution poultry processing plays in the development of physical agents and ergonomic stress related occupational diseases in poultry abattoir processing workers. The impact includes noise-induced hearing loss, increased blood pressure, menstrual and work related upper limb disorders. These are summarised as a quick reference guide for poultry abattoir owners, abattoir workers, poultry associations, occupational hygienists and medical practitioners to assist in the safer management of occupational health in poultry abattoirs. PMID- 26861375 TI - Health Risk Assessment for Inhalation Exposure to Methyl Tertiary Butyl Ether at Petrol Stations in Southern China. AB - Methyl tertiary butyl ether (MTBE), a well known gasoline additive, is used in China nationwide to enhance the octane number of gasoline and reduce harmful exhaust emissions, yet little is known regarding the potential health risk associated with occupational exposure to MTBE in petrol stations. In this study, 97 petrol station attendants (PSAs) in southern China were recruited for an assessment of the health risk associated with inhalation exposure to MTBE. The personal exposure levels of MTBE were analyzed by Head Space Solid Phase Microextraction GC/MS, and the demographic characteristics of the PSAs were investigated. Cancer and non-cancer risks were calculated with the methods recommended by the United States Environmental Protection Agency. The results showed that the exposure levels of MTBE in operating workers were much higher than among support staff (p < 0.01) and both were lower than 50 ppm (an occupational threshold limit value). The calculated cancer risks (CRs) at the investigated petrol stations was 0.170 to 0.240 per 106 for operating workers, and 0.026 to 0.049 per 106 for support staff, which are below the typical target range for risk management of 1 * 10(-6) to 1 * 10(-4); The hazard quotients (HQs) for all subjects were <1. In conclusion, our study indicates that the MTBE exposure of PSAs in southern China is in a low range which does not seem to be a significant health risk. PMID- 26861376 TI - Interventions to Support System-level Implementation of Health Promoting Schools: A Scoping Review. AB - Health promoting schools (HPS) is recognized globally as a multifaceted approach that can support health behaviours. There is increasing clarity around factors that influence HPS at a school level but limited synthesized knowledge on the broader system-level elements that may impact local implementation barriers and support uptake of a HPS approach. This study comprised a scoping review to identify, summarise and disseminate the range of research to support the uptake of a HPS approach across school systems. Two reviewers screened and extracted data according to inclusion/exclusion criteria. Relevant studies were identified using a multi-phased approach including searching electronic bibliographic databases of peer reviewed literature, hand-searching reference lists and article recommendations from experts. In total, 41 articles met the inclusion criteria for the review, representing studies across nine international school systems. Overall, studies described policies that provided high-level direction and resources within school jurisdictions to support implementation of a HPS approach. Various multifaceted organizational and professional interventions were identified, including strategies to enable and restructure school environments through education, training, modelling and incentives. A systematic realist review of the literature may be warranted to identify the types of intervention that work best for whom, in what circumstance to create healthier schools and students. PMID- 26861377 TI - Diabetes Mellitus, Arterial Wall, and Cardiovascular Risk Assessment. AB - Diabetes mellitus is an independent risk factor for atherothrombotic cardiovascular disease. Adults with diabetes are two to four times more likely to develop heart disease or stroke than adults without diabetes. The two major features of diabetes, i.e., hyperglycemia and insulin-resistance, trigger arterial stiffening and increase the susceptibility of the arterial wall to atherosclerosis at any given age. These pathological changes in the arterial wall may provide a functional and structural background for cardiovascular events. The present paper provides a critical overview of the clinical evidence linking diabetes-related metabolic abnormalities to cardiovascular risk, debates the pathophysiologic mechanisms through which insulin resistance and hyperglycemia may affect the arterial wall, and discusses the associations between vascular biomarkers, metabolic abnormalities and cardiovascular events. PMID- 26861378 TI - Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis. AB - Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (p< 0.000001) following arsenic exposure: inorganic arsenic (iAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; p< 0.00001) and MMA (SMD: 0.49; 95% CI: 0.21 0.77; p = 0.0006) also increase, while the percentage of DMA (SMD: -0.57; 95% CI: -0.80--0.31; p< 0.0001), primary methylation index (SMD: -0.57; 95% CI: -0.94- 0.20; p = 0.002), and secondary methylation index (SMD: -0.27; 95% CI: -0.46- 0.90; p = 0.004) decrease. Smoking, drinking, and older age can reduce arsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process. PMID- 26861379 TI - The Association of Exposure to Point-of-Sale Tobacco Marketing with Quit Attempt and Quit Success: Results from a Prospective Study of Smokers in the United States. AB - The aim was to assess the association of exposure to point-of-sale (POS) tobacco marketing with quit attempt and quit success in a prospective study of smokers in the United States. Data were collected via telephone-interview on exposure to POS tobacco marketing, sociodemographic and smoking-related variables from 999 smokers in Omaha, Nebraska, in the United States. Exposure to POS tobacco marketing was measured by asking respondents three questions about noticing pack displays, advertisements, and promotions in their respective neighborhoods stores. These three variables were combined into a scale of exposure to POS tobacco marketing. About 68% of the respondents participated in a six-month follow-up phone interview and provided data on quit attempts and smoking cessation. At the six-month follow-up, 39.9% of respondents reported to have made a quit attempt, and 21.8% of those who made a quit attempt succeeded in quitting. Exposure to POS marketing at baseline was not associated with the probability of having made a quit attempt as reported at the six-month follow-up (p = 0.129). However, higher exposure to POS marketing was associated with a lower probability of quit success among smokers who reported to have attempted to quit smoking at six-month follow-up (p = 0.006). Exposure to POS tobacco marketing is associated with lower chances of successfully quitting smoking. Policies that reduce the amount of exposure to POS marketing might result in higher smoking cessation rates. PMID- 26861380 TI - Fabrication of Te and Te-Au Nanowires-Based Carbon Fiber Fabrics for Antibacterial Applications. AB - Pathogenic bacteria that give rise to diseases every year remain a major health concern. In recent years, tellurium-based nanomaterials have been approved as new and efficient antibacterial agents. In this paper, we developed the approach to directly grow tellurium nanowires (Te NWs) onto commercial carbon fiber fabrics and demonstrated their antibacterial activity. Those Te NWs can serve as templates and reducing agents for gold nanoparticles (Au NPs) to deposit. Three different Te-Au NWs with varied concentration of Au NPs were synthesized and showed superior antibacterial activity and biocompability. These results indicate that the as-prepared carbon fiber fabrics with Te and Te-Au NWs can become antimicrobial clothing products in the near future. PMID- 26861381 TI - To Infection and Beyond: The Multi-Pronged Anti-Cancer Mechanisms of Oncolytic Viruses. AB - Over the past 1-2 decades we have witnessed a resurgence of efforts to therapeutically exploit the attributes of lytic viruses to infect and kill tumor cells while sparing normal cells. We now appreciate that the utility of viruses for treating cancer extends far beyond lytic cell death. Viruses are also capable of eliciting humoral and cellular innate and adaptive immune responses that may be directed not only at virus-infected cells but also at uninfected cancer cells. Here we review our current understanding of this bystander effect, and divide the mechanisms into lytic, cytokine, innate cellular, and adaptive phases. Knowing the key pathways and molecular players during virus infection in the context of the cancer microenvironment will be critical to devise strategies to maximize the therapeutic effects of oncolytic viroimmunotherapy. PMID- 26861382 TI - Generation of Recombinant Polioviruses Harboring RNA Affinity Tags in the 5' and 3' Noncoding Regions of Genomic RNAs. AB - Despite being intensely studied for more than 50 years, a complete understanding of the enterovirus replication cycle remains elusive. Specifically, only a handful of cellular proteins have been shown to be involved in the RNA replication cycle of these viruses. In an effort to isolate and identify additional cellular proteins that function in enteroviral RNA replication, we have generated multiple recombinant polioviruses containing RNA affinity tags within the 3' or 5' noncoding region of the genome. These recombinant viruses retained RNA affinity sequences within the genome while remaining viable and infectious over multiple passages in cell culture. Further characterization of these viruses demonstrated that viral protein production and growth kinetics were unchanged or only slightly altered relative to wild type poliovirus. However, attempts to isolate these genetically-tagged viral genomes from infected cells have been hindered by high levels of co-purification of nonspecific proteins and the limited matrix-binding efficiency of RNA affinity sequences. Regardless, these recombinant viruses represent a step toward more thorough characterization of enterovirus ribonucleoprotein complexes involved in RNA replication. PMID- 26861383 TI - Big Data Offers Novel Insights for Oncolytic Virus Immunotherapy. AB - Large-scale assays, such as microarrays, next-generation sequencing and various "omics" technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. Yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy (OVIT) in the cancer setting. Tracking immune signatures at the tumour site can create a snapshot or longitudinally analyse immune cell activation, infiltration and functionality within global populations or individual cells. Mapping immune changes over the course of oncolytic biotherapy from initial infection to tumour stabilisation/regression through to long-term cure or escape/relapse-has the potential to generate important therapeutic insights around virus-host interactions. Further, correlating such immune signatures with specific tumour outcomes has significant value for guiding the development of novel oncolytic virus immunotherapy strategies. Here, we provide insights for OVIT from large-scale analyses of immune populations in the infection, vaccination and immunotherapy setting. We analyse several approaches to manipulating immune engagement during OVIT. We further explore immunocentric changes in the tumour tissue following immunotherapy, and compile several immune signatures of therapeutic success. Ultimately, we highlight clinically relevant large-scale approaches with the potential to strengthen future oncolytic strategies to optimally engage the immune system. PMID- 26861384 TI - A KDEL Retrieval System for ER-Golgi Transport of Japanese Encephalitis Viral Particles. AB - Evidence has emerged that RNA viruses utilize the host secretory pathway for processing and trafficking mature viral particles and for exiting the infected cells. Upon completing the complex assembly process, the viral particles take advantage of the cellular secretory trafficking machinery for their intracellular trafficking toward the Golgi organelle and budding or export of virions. In this study, we showed that Japanese encephalitis virus (JEV)-induced extracellular GRP78 contains no KDEL motif using an anti-KDEL-specific antibody. Overexpression of the KDEL-truncated GRP78 in the GPR78 knocked down cells significantly reduced JEV infectivity, suggesting that the KDEL motif is required for GRP78 function in the release of JE viral particles. In addition, we demonstrated the KDELR protein, an ER-Golgi retrieval system component, is associated with viral envelope proteins and is engaged in the subcellular localization of viral particles in Golgi. More importantly, accumulation of intracellular virions was observed in the KDELR knocked down cells, indicating that the KDELR protein mediated the intracellular trafficking of JE viral particles. Altogether, we demonstrated that intracellular trafficking of JE assembled viral particles was mediated by the host ER-Golgi retrieval system prior to exit by the secretory pathway. PMID- 26861385 TI - Vitamin D Intake and Status in 6-Year-Old Icelandic Children Followed up from Infancy. AB - High serum 25-hydroxyvitamin D (25(OH)D) levels have been observed in infants in Nordic countries, likely due to vitamin D supplement use. Internationally, little is known about tracking vitamin D status from infancy to childhood. Following up 1-year-old infants in our national longitudinal cohort, our aims were to study vitamin D intake and status in healthy 6-year-old Icelandic children (n = 139) and to track vitamin D status from one year of age. At six years, the mean 25(OH)D level was 56.5 nmol/L (SD 17.9) and 64% of children were vitamin D sufficient (25(OH)D >= 50 nmol/L). A logistic regression model adjusted for gender and breastfeeding showed that higher total vitamin D intake (Odds ratio (OR) = 1.27, 95% confidence interval (CI) = 1.08-1.49), blood samples collected in summer (OR = 8.88, 95% CI = 1.83-43.23) or autumn (OR = 5.64, 95% CI = 1.16 27.32) compared to winter/spring, and 25(OH)D at age one (OR = 1.02, 95% CI = 1.002-1.04) were independently associated with vitamin D sufficiency at age six. The correlation between 25(OH)D at age one and six was 0.34 (p = 0.003). Our findings suggest that vitamin D status in infancy, current vitamin D intake and season are predictors of vitamin D status in early school age children. Our finding of vitamin D status tracking from infancy to childhood provides motivation for further studies on tracking and its clinical significance. PMID- 26861386 TI - High Prevalence of Vitamin D Deficiency among Pregnant Saudi Women. AB - Vitamin D deficiency has emerged as a public health problem worldwide due to its important role in health and disease. The present work is intended to examine prevalence of vitamin D deficiency among pregnant Saudi women and related risk factors. A cross-sectional study was carried out at King Fahad Medical City in Riyadh, Saudi Arabia. Serum 25-hydroxy vitamin D (25(OH)D) was measured by enzyme linked immunosorbent assay in 160 pregnant women during the first trimester of pregnancy. Socio-demographic, lifestyle and maternal characteristics were collected and vitamin D intake was assessed using a 24-h dietary recall. Weight and height were measured using standardized methods. Vitamin D deficiency (25(OH)D < 50 nmol/L) and insufficiency (25(OH)D = 50-74 nmol/L) were reported in 50% and 43.8% of the study sample, respectively. Median serum 25(OH)D concentration was 49.9 nmol/L. Adequate vitamin D intake (>=600 IU/day) was reported among only 8.1% of pregnant women. Age group, educational level, sun exposure frequency and daytime and daily practice of exercise were significantly associated with vitamin D status. Overall, vitamin D deficiency was common among pregnant Saudi women in Riyadh. Steps should be taken to address the current situation, including increased sunlight exposure, consumption of fatty fish, and vitamin D supplements. PMID- 26861387 TI - Exogenous Glutamine in Respiratory Diseases: Myth or Reality? AB - Several respiratory diseases feature increased inflammatory response and catabolic activity, which are associated with glutamine depletion; thus, the benefits of exogenous glutamine administration have been evaluated in clinical trials and models of different respiratory diseases. Recent reviews and meta analyses have focused on the effects and mechanisms of action of glutamine in a general population of critical care patients or in different models of injury. However, little information is available about the role of glutamine in respiratory diseases. The aim of the present review is to discuss the evidence of glutamine depletion in cystic fibrosis (CF), asthma, chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and lung cancer, as well as the results of exogenous glutamine administration in experimental and clinical studies. Exogenous glutamine administration might be beneficial in ARDS, asthma, and during lung cancer treatment, thus representing a potential therapeutic tool in these conditions. Further experimental and large randomized clinical trials focusing on the development and progression of respiratory diseases are necessary to elucidate the effects and possible therapeutic role of glutamine in this setting. PMID- 26861388 TI - Selenium and Metabolic Disorders: An Emphasis on Type 2 Diabetes Risk. AB - Selenium (Se) is a micronutrient that maintains biological functions through the action of Se containing proteins known as selenoproteins. Due to the known antioxidant effects of Se, supplements containing Se have been on the rise. While Se supplementation may be beneficial for Se deficient populations, few are at risk for Se deficiency due to the transportation of food from Se-rich regions and the rise of Se-enriched foods. Alarmingly, Se supplementation may have adverse effects in people who already receive an adequate Se supply. Specifically, an increased risk of type 2 diabetes has been reported in individuals with high baseline Se levels. However, this effect was restricted to males, suggesting the relationship between Se and glucose homeostasis may be sexually dimorphic. This review will discuss the current understanding of the interaction between Se and glucose homeostasis, including any sex differences that have been described. PMID- 26861389 TI - A Common Variant in the SETD7 Gene Predicts Serum Lycopene Concentrations. AB - Dietary intake and higher serum concentrations of lycopene have been associated with lower incidence of prostate cancer and other chronic diseases. Identifying determinants of serum lycopene concentrations may thus have important public health implications. Prior studies have suggested that serum lycopene concentrations are under partial genetic control. The goal of this research was to identify genetic predictors of serum lycopene concentrations using the genome wide association study (GWAS) approach among a sample of 441 Old Order Amish adults that consumed a controlled diet. Linear regression models were utilized to evaluate associations between genetic variants and serum concentrations of lycopene. Variant rs7680948 on chromosome 4, located in the intron region of the SETD7 gene, was significantly associated with serum lycopene concentrations (p = 3.41 * 10(-9)). Our findings also provided nominal support for the association previously noted between SCARB1 and serum lycopene concentrations, although with a different SNP (rs11057841) in the region. This study identified a novel locus associated with serum lycopene concentrations and our results raise a number of intriguing possibilities regarding the nature of the relationship between SETD7 and lycopene, both of which have been independently associated with prostate cancer. Further investigation into this relationship might help provide greater mechanistic understanding of these associations. PMID- 26861390 TI - Psoralea corylifolia L. Seed Extract Attenuates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice. AB - Nonalcoholic fatty liver disease (NAFLD), along with obesity, is increasing world wide and is one of the major causes of chronic hepatic disease. The present study evaluated the ameliorative effect of extract of Psoralea corylifolia L. seed (PCS) on high fat diet-induced NAFLD in C57BL/6 mice after daily administration at 300 or 500 mg/kg for 12 weeks. Treatment with PCS extract significantly reduced body weight and blood glucose levels and improved glucose tolerance and insulin sensitivity. In addition, PCS extract treatment significantly attenuated lipid accumulation in liver and adipose tissue and reduced serum lipid and hepatic triglyceride levels. Furthermore, the expression of lipogenic genes and inflammatory genes were reduced, and the expression of fat oxidation-related genes was increased in the liver of PCS extract-treated mice compared with control mice. Our study suggests the therapeutic potential of PCS extract for NAFLD by inhibiting lipid accumulation and inflammation in liver. PMID- 26861392 TI - Cancer Therapy by Catechins Involves Redox Cycling of Copper Ions and Generation of Reactive Oxygen species. AB - Catechins, the dietary phytochemicals present in green tea and other beverages, are considered to be potent inducers of apoptosis and cytotoxicity to cancer cells. While it is believed that the antioxidant properties of catechins and related dietary agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, these properties cannot account for apoptosis induction and chemotherapeutic observations. Catechin (C), epicatechin (EC), epigallocatechin (EGC) and epigallocatechin-3-gallate (EGCG) are the four major constituents of green tea. In this article, using human peripheral lymphocytes and comet assay, we show that C, EC, EGC and EGCG cause cellular DNA breakage and can alternatively switch to a prooxidant action in the presence of transition metals such as copper. The cellular DNA breakage was found to be significantly enhanced in the presence of copper ions. Catechins were found to be effective in providing protection against oxidative stress induced by tertbutylhydroperoxide, as measured by oxidative DNA breakage in lymphocytes. The prooxidant action of catechins involved production of hydroxyl radicals through redox recycling of copper ions. We also determined that catechins, particularly EGCG, inhibit proliferation of breast cancer cell line MDA-MB-231 leading to a prooxidant cell death. Since it is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies, cancer cells would be more subject to redox cycling between copper ions and catechins to generate reactive oxygen species (ROS) responsible for DNA breakage. Such a copper dependent prooxidant cytotoxic mechanism better explains the anticancer activity and preferential cytotoxicity of dietary phytochemicals against cancer cells. PMID- 26861391 TI - The Reciprocal Interactions between Polyphenols and Gut Microbiota and Effects on Bioaccessibility. AB - As of late, polyphenols have increasingly interested the scientific community due to their proposed health benefits. Much of this attention has focused on their bioavailability. Polyphenol-gut microbiota interactions should be considered to understand their biological functions. The dichotomy between the biotransformation of polyphenols into their metabolites by gut microbiota and the modulation of gut microbiota composition by polyphenols contributes to positive health outcomes. Although there are many studies on the in vivo bioavailability of polyphenols, the mutual relationship between polyphenols and gut microbiota is not fully understood. This review focuses on the biotransformation of polyphenols by gut microbiota, modulation of gut microbiota by polyphenols, and the effects of these two-way mutual interactions on polyphenol bioavailability, and ultimately, human health. PMID- 26861393 TI - A New Member of Gamma-Conotoxin Family Isolated from Conus princeps Displays a Novel Molecular Target. AB - A novel conotoxin, named as PiVIIA, was isolated from the venom of Conus princeps, a marine predatory cone snail collected in the Pacific Southern Coast of Mexico. Chymotryptic digest of the S-alkylated peptide in combination with liquid chromatography coupled to tandem mass spectrometry, were used to define the sequencing of this peptide. Eleven N-terminal amino acids were verified by automated Edman degradation. PiVIIA is a 25-mer peptide (CDAOTHYCTNYWgammaCCSGYCgammaHSHCW) with six cysteine residues forming three disulphide bonds, a hydroxyproline (O) and two gamma carboxyglutamic acid (gamma) residues. Based on the arrangement of six Cys residues (C-C-CC-C-C), this conotoxin might belong to the O2-superfamily. Moreover, PiVIIA has a conserved motif (-gammaCCS-) that characterizes gamma-conotoxins from molluscivorous Conus. Peptide PiVIIA has 45% sequence identity with gamma-PnVIIA-the prototype of this family. Biological activity of PiVIIA was assessed by voltage-clamp recording in rat dorsal root ganglion neurons. Perfusion of PiVIIA in the uM range produces a significant increase in the Ca(2+) currents, without significantly modifying the Na+, K+ or proton-gated acid sensing ionic currents. These results indicate that PiVIIA is a new conotoxin whose activity deserves further studies to define its potential use as a positive modulator of neuronal activity. PMID- 26861395 TI - Teratogenicity of Ochratoxin A and the Degradation Product, Ochratoxin alpha, in the Zebrafish (Danio rerio) Embryo Model of Vertebrate Development. AB - Ochratoxins, and particularly ochratoxin A (OTA), are toxic fungal-derived contaminants of food and other agricultural products. Growing evidence supports the degradation of OTA by chemical, enzymatic and/or microbial means as a potential approach to remove this mycotoxin from food products. In particular, hydrolysis of OTA to ochratoxin alpha (OTalpha) and phenylalanine is the presumptive product of degradation in most cases. In the current study, we employed the zebrafish (Danio rerio) embryo, as a model of vertebrate development to evaluate, the teratogenicity of OTA and OTalpha. These studies show that OTA is potently active in the zebrafish embryo toxicity assay (ZETA), and that toxicity is both concentration- and time-dependent with discernible and quantifiable developmental toxicity observed at nanomolar concentrations. On the other hand, OTalpha had no significant effect on embryo development at all concentrations tested supporting a decreased toxicity of this degradation product. Taken together, these results suggest that ZETA is a useful, and highly sensitive, tool for evaluating OTA toxicity, as well as its degradation products, toward development of effective detoxification strategies. Specifically, the results obtained with ZETA, in the present study, further demonstrate the toxicity of OTA, and support its degradation via hydrolysis to OTalpha as an effective means of detoxification. PMID- 26861394 TI - Apoptosis Activation in Human Lung Cancer Cell Lines by a Novel Synthetic Peptide Derived from Conus californicus Venom. AB - Lung cancer is one of the most common types of cancer in men and women and a leading cause of death worldwide resulting in more than one million deaths per year. The venom of marine snails Conus contains up to 200 pharmacologically active compounds that target several receptors in the cell membrane. Due to their diversity and specific binding properties, Conus toxins hold great potential as source of new drugs against cancer. We analyzed the cytotoxic effect of a 17 amino acid synthetic peptide (s-cal14.1a) that is based on a native toxin (cal14.1a) isolated from the sea snail Conus californicus. Cytotoxicity studies in four lung cancer cell lines were complemented with measurement of gene expression of apoptosis-related proteins Bcl-2, BAX and the pro-survival proteins NFkappaB-1 and COX-2, as well as quantification of caspase activity. Our results showed that H1299 and H1437 cell lines treated with s-call4.1a had decreased cell viability, activated caspases, and reduced expression of the pro-survival protein NFkappaB-1. To our knowledge, this is the first report describing activation of apoptosis in human lung cancer cell lines by s-cal14.1a and we offer insight into the possible mechanism of action. PMID- 26861396 TI - Acetylated Deoxynivalenol Generates Differences of Gene Expression that Discriminate Trichothecene Toxicity. AB - Deoxynivalenol (DON), which is a toxic secondary metabolite generated by Fusarium species, is synthesized through two separate acetylation pathways. Both acetylation derivatives, 3-acetyl-DON (3ADON) and 15-acetyl-DON (15ADON), also contaminate grain and corn widely. These derivatives are deacetylated via a variety of processes after ingestion, so it has been suggested that they have the same toxicity as DON. However, in the intestinal entry region such as the duodenum, the derivatives might come into contact with intestinal epithelium cells because metabolism by microflora or import into the body has not progressed. Therefore, the differences of toxicity between DON and these derivatives need to be investigated. Here, we observed gene expression changes in the yeast pdr5Delta mutant strain under concentration-dependent mycotoxin exposure conditions. 15ADON exposure induced significant gene expression changes and DON exposure generally had a similar but smaller effect. However, the glucose transporter genes HXT2 and HXT4 showed converse trends. 3ADON also induced a different expression trend in these genes than DON and 15ADON. These differences in gene expression suggest that DON and its derivatives have different effects on cells. PMID- 26861398 TI - Computed Tomography and Ultrasounds for the Follow-up of Hepatocellular Carcinoma Ablation: What You Need to Know. AB - Image-guided tumor ablation provides curative treatment in properly selected patients or appropriate therapeutic options whenever surgical techniques are precluded. Tumor response assessment post ablation is important in determining treatment success and future therapy. Accurate interpretation of post-ablation imaging findings is crucial for therapeutic and follow-up strategies. Computed Tomography (CT) and Ultrasound (US) play important roles in patients' follow-up post liver thermal ablation therapies. Contrast-enhanced ultrasound (CEUS) can provide valuable information on the ablation effects faster and at a lower cost than computed tomography or magnetic resonance imaging. However, a disadvantage is that the technique cannot examine total liver parenchyma for disease progression as CT and Magnetic Resonance (MR) imaging can. Follow-up strategies for assessment of tumor response includes contrast enhanced multiphasic (non contrast, arterial, portal, delayed phases) imaging with Computed Tomography at three, six, and 12 months post ablation session and annually ever since in order to prove sustained effectiveness of the ablation or detect progression. PMID- 26861397 TI - Functions of Rab Proteins at Presynaptic Sites. AB - Presynaptic neurotransmitter release is dominated by the synaptic vesicle (SV) cycle and entails the biogenesis, fusion, recycling, reformation or turnover of synaptic vesicles-a process involving bulk movement of membrane and proteins. As key mediators of membrane trafficking, small GTPases from the Rab family of proteins play critical roles in this process by acting as molecular switches that dynamically interact with and regulate the functions of different sets of macromolecular complexes involved in each stage of the cycle. Importantly, mutations affecting Rabs, and their regulators or effectors have now been identified that are implicated in severe neurological and neurodevelopmental disorders. Here, we summarize the roles and functions of presynaptic Rabs and discuss their involvement in the regulation of presynaptic function. PMID- 26861399 TI - Replacing Myalgic Encephalomyelitis and Chronic Fatigue Syndrome with Systemic Exercise Intolerance Disease Is Not the Way forward. AB - Myalgic encephalomyelitis (ME), described in the medical literature since 1938, is characterized by distinctive muscular symptoms, neurological symptoms, and signs of circulatory impairment. The only mandatory feature of chronic fatigue syndrome (CFS), introduced in 1988 and redefined in 1994, is chronic fatigue, which should be accompanied by at least four or more out of eight "additional" symptoms. The use of the abstract, polythetic criteria of CFS, which define a heterogeneous patient population, and self-report has hampered both scientific progress and accurate diagnosis. To resolve the "diagnostic impasse" the Institute of Medicine proposes that a new clinical entity, systemic exercise intolerance disease (SEID), should replace the clinical entities ME and CFS. However, adopting SEID and its defining symptoms, does not resolve methodological and diagnostic issues. Firstly, a new diagnostic entity cannot replace two distinct, partially overlapping, clinical entities such as ME and CFS. Secondly, due to the nature of the diagnostic criteria, the employment of self-report, and the lack of criteria to exclude patients with other conditions, the SEID criteria seem to select an even more heterogeneous patient population, causing additional diagnostic confusion. This article discusses methodological and diagnostic issues related to SEID and proposes a methodological solution for the current "diagnostic impasse". PMID- 26861400 TI - Serotonin 2A Receptor SNP rs7330461 Association with Treatment Response to Pomaglumetad Methionil in Patients with Schizophrenia. AB - This study aims to confirm the initial pharmacogenetic finding observed within the clinical proof-of-concept trial of an enhanced response to treatment with pomaglumetad methionil (LY2140023 monohydrate) in Caucasian schizophrenia patients homozygous for T/T at single nucleotide polymorphism rs7330461 in the serotonin (5-hydroxytryptamine) 2A receptor gene compared to A/A homozygous patients. The effect of the rs7330461 genotype on the response to pomaglumetad methionil treatment was assessed in three additional clinical trials and in an integrated analysis. Overall, this study includes data from 1115 Caucasian patients for whom genotyping information for rs7330461 was available, consisting of 513 A/A homozygous, 466 A/T heterozygous and 136 T/T homozygous patients. Caucasian T/T homozygous patients showed significantly (p <= 0.05) greater improvement in Positive and Negative Syndrome Scale (PANSS) total scores during treatment with pomaglumetad methionil 40 mg twice daily compared to A/A homozygous patients. Additionally, T/T homozygous patients receiving pomaglumetad methionil had significantly (p <= 0.05) greater improvements in PANSS total scores compared to placebo and similar improvements as T/T homozygous patients receiving standard-of-care (SOC) treatment. The findings reported here in conjunction with prior reports show that in Caucasian patients with schizophrenia, the T/T genotype at rs7330461 is consistently associated with an increased treatment response to pomaglumetad methionil compared to the A/A genotype. PMID- 26861401 TI - Biomimickry of UPEC Cytoinvasion: A Novel Concept for Improved Drug Delivery in UTI. AB - Urinary tract infections (UTIs) are among the most common bacterial infections. In an increasing number of cases, pathogen (multi-)resistance hampers durable treatment success via the standard therapies. On the functional level, the activity of urinary excreted antibiotics is compromized by the efficient tissue colonization mechanism of uropathogenic Escherichia coli (UPEC). Advanced drug delivery systems aim at exploiting a glycan-mediated targeting mechanism, similar to the UPEC invasion pathway, to increase bioavailability. This may be realized by conjugation of intravesically applied drugs or drug carriers to chosen plant lectins. Higher local drug concentrations in or nearby bacterial reservoirs may be gained, with higher chances for complete eradication. In this study, preliminary parameters to clarify the potential of this biorecognitive approach were evaluated. Glycan-triggered interaction cascades and uptake processes of several plant lectins with distinct carbohydrate specificities were characterized, and wheat germ agglutinin (WGA) could be identified as the most promising targeter for crossing the urothelial membrane barrier. In partially differentiated primary cells, intracellular accumulation sites were largely identical for GlcNAc- and Mannose-specific lectins. This indicates that WGA mediated delivery may also enter host cells via the FimH-dependent uptake pathway. PMID- 26861402 TI - Neutrophil Migration into the Infected Uroepithelium Is Regulated by the Crosstalk between Resident and Helper Macrophages. AB - The antibacterial defense against infections depends on the cooperation between distinct phagocytes of the innate immune system, namely macrophages and neutrophils. However, the mechanisms driving this cooperation are incompletely understood. In this study we describe the crosstalk between Ly6C+ and Ly6C(-) macrophage-subtypes and neutrophils in the context of urinary tract infection (UTI) with uropathogenic E. coli (UPEC). Ly6C(-) macrophages acted as tissue resident sentinels and attracted circulating phagocytes by chemokines. Ly6C+ macrophages produced tumor necrosis factor (TNF) that licensed Ly6C(-) macrophages to release preformed CXCL2, which in turn caused matrix metalloproteinases (MMP-9) secretion by neutrophils to enable transepithelial migration. PMID- 26861403 TI - First Description of Infection of Caprine Herpesvirus 1 (CpHV-1) in Goats in Mainland France. AB - The purpose of this study was to investigate the epidemiological situation of the caprine herpesvirus 1 (CpHV-1) infection in nine districts in mainland France, mostly in the south, near Italy or Spain, where high seroprevalence has been observed. Two more central areas were also included in the study. The serosurvey was carried out in 9564 goats (275 herds) using bovine herpesvirus 1 (BoHV-1) glycoprotein B and E ELISAs. To confirm the presence of specific CpHV-1 antibodies, some of the samples were tested in neutralization assay. Results demonstrate, for the first time, CpHV-1 infection in goat herds on the French mainland. The analysis found cases of alphaherpesviruses infection in each district studied, with different levels of seroprevalence observed within each district (ranging from 0.2% to 31.56% at an individual level and from 9% to 46.2% for herd seroprevalence). Moreover, in the Alpes-Maritimes district, the seroprevalence seemed to be higher in older goats (79.45% of animals 6 years old or more) than in younger animals (40.99% of one-year-olds). This result suggests frequent virus re-excretion and circulation in herds. Results analysis also shows that the seroprevalence was higher when the herd size increased. In addition, the first French CpHV-1 strain was isolated from nasal swabs taken on an infected goat. The data reported herein demonstrate that CpHV-1 circulates in mainland France, which should henceforth be taken into consideration in cases of unexplained abortion in goats. PMID- 26861405 TI - Influence of Global and Local Membrane Curvature on Mechanosensitive Ion Channels: A Finite Element Approach. AB - Mechanosensitive (MS) channels are ubiquitous molecular force sensors that respond to a number of different mechanical stimuli including tensile, compressive and shear stress. MS channels are also proposed to be molecular curvature sensors gating in response to bending in their local environment. One of the main mechanisms to functionally study these channels is the patch clamp technique. However, the patch of membrane surveyed using this methodology is far from physiological. Here we use continuum mechanics to probe the question of how curvature, in a standard patch clamp experiment, at different length scales (global and local) affects a model MS channel. Firstly, to increase the accuracy of the Laplace's equation in tension estimation in a patch membrane and to be able to more precisely describe the transient phenomena happening during patch clamping, we propose a modified Laplace's equation. Most importantly, we unambiguously show that the global curvature of a patch, which is visible under the microscope during patch clamp experiments, is of negligible energetic consequence for activation of an MS channel in a model membrane. However, the local curvature (RL < 50) and the direction of bending are able to cause considerable changes in the stress distribution through the thickness of the membrane. Not only does local bending, in the order of physiologically relevant curvatures, cause a substantial change in the pressure profile but it also significantly modifies the stress distribution in response to force application. Understanding these stress variations in regions of high local bending is essential for a complete understanding of the effects of curvature on MS channels. PMID- 26861406 TI - Hypoxia, Epithelial-Mesenchymal Transition, and TET-Mediated Epigenetic Changes. AB - Tumor hypoxia is a pathophysiologic outcome of disrupted microcirculation with inadequate supply of oxygen, leading to enhanced proliferation, epithelial mesenchymal transition (EMT), metastasis, and chemo-resistance. Epigenetic changes induced by hypoxia are well documented, and they lead to tumor progression. Recent advances show that DNA demethylation mediated by the Ten eleven translocation (TET) proteins induces major epigenetic changes and controls key steps of cancer development. TET enzymes serve as 5mC (5-methylcytosine) specific dioxygenases and cause DNA demethylation. Hypoxia activates the expression of TET1, which also serves as a co-activator of HIF-1alpha transcriptional regulation to modulate HIF-1alpha downstream target genes and promote epithelial-mesenchymal transition. As HIF is a negative prognostic factor for tumor progression, hypoxia-activated prodrugs (HAPs) may provide a favorable therapeutic approach to lessen hypoxia-induced malignancy. PMID- 26861407 TI - Potential Benefits of Omega-3 Fatty Acids in Non-Melanoma Skin Cancer. AB - Considerable circumstantial evidence has accrued from both experimental animal and human clinical studies that support a role for omega-3 fatty acids (FA) in the prevention of non-melanoma skin cancer (NMSC). Direct evidence from animal studies has shown that omega-3 FA inhibit ultraviolet radiation (UVR) induced carcinogenic expression. In contrast, increasing levels of dietary omega-6 FA increase UVR carcinogenic expression, with respect to a shorter tumor latent period and increased tumor multiplicity. Both omega-6 and omega-3 FA are essential FA, necessary for normal growth and maintenance of health and although these two classes of FA exhibit only minor structural differences, these differences cause them to act significantly differently in the body. Omega-6 and omega-3 FA, metabolized through the lipoxygenase (LOX) and cyclooxygenase (COX) pathways, lead to differential metabolites that are influential in inflammatory and immune responses involved in carcinogenesis. Clinical studies have shown that omega-3 FA ingestion protects against UVR-induced genotoxicity, raises the UVR mediated erythema threshold, reduces the level of pro-inflammatory and immunosuppressive prostaglandin E2 (PGE2) in UVR-irradiated human skin, and appears to protect human skin from UVR-induced immune-suppression. Thus, there is considerable evidence that omega-3 FA supplementation might be beneficial in reducing the occurrence of NMSC, especially in those individuals who are at highest risk. PMID- 26861408 TI - Decoding the Secret of Cancer by Means of Extracellular Vesicles. AB - One of the recent outstanding developments in cancer biology is the emergence of extracellular vesicles (EVs). EVs, which are small membrane vesicles that contain proteins, mRNAs, long non-coding RNAs, and microRNAs (miRNAs), are secreted by a variety of cells and have been revealed to play an important role in intercellular communications. These molecules function in the recipient cells; this has brought new insight into cell-cell communication. Recent reports have shown that EVs contribute to cancer cell development, including tumor initiation, angiogenesis, immune surveillance, drug resistance, invasion, metastasis, maintenance of cancer stem cells, and EMT phenotype. In this review, I will summarize recent studies on EV-mediated miRNA transfer in cancer biology. Furthermore, I will also highlight the possibility of novel diagnostics and therapy using miRNAs in EVs against cancer. PMID- 26861409 TI - Aboveground Net Primary Productivity in a Riparian Wetland Following Restoration of Hydrology. AB - This research presents the initial results of the effects of hydrological restoration on forested wetlands in the Mississippi alluvial plain near Memphis, Tennessee. Measurements were carried out in a secondary channel, the Loosahatchie Chute, in which rock dikes were constructed in the 1960s to keep most flow in the main navigation channel. In 2008-2009, the dikes were notched to allow more flow into the secondary channel. Study sites were established based on relative distance downstream of the notched dikes. Additionally, a reference site was established north of the Loosahatchie Chute where the dikes remained unnotched. We compared various components of vegetation composition and productivity at sites in the riparian wetlands for two years. Salix nigra had the highest Importance Value at every site. Species with minor Importance Values were Celtis laevigata, Acer rubrum, and Plantanus occidentalis. Productivity increased more following the introduction of river water in affected sites compared to the reference. Aboveground net primary productivity was highest at the reference site (2926 +/- 458.1 g.m(-2).year(-1)), the intact site; however, there were greater increase at the sites in the Loosahatchie Chute, where measurements ranged from 1197.7 +/- 160.0 g m(-2).year(-1).to 2874.2 +/- 794.0 g.m(-2).year(-1). The site furthest from the notching was the most affected. Pulsed inputs into these wetlands may enhance forested wetland productivity. Continued monitoring will quantify impacts of restored channel hydrology along the Mississippi River. PMID- 26861411 TI - Deep penetrating nevus of the plantar surface: report of a case with dermatoscopic features. PMID- 26861412 TI - Unencapsulated Air-stable Organic Field Effect Transistor by All Solution Processes for Low Power Vapor Sensing. AB - With its excellent mechanical flexibility, low-cost and low-temperature processing, the solution processed organic field-effect transistor (OFET) is a promising platform technology for developing ubiquitous sensor applications in digital health, environment monitoring and Internet of Things. However, a contradiction between achieving low voltage operation and having stable performance severely hinder the technology to become commercially viable. This work shows that, by reducing the sub-gap density of states (DOS) at the channel for low operation voltage and using a proper low-k non-polar polymer dielectric layer, such an issue can be addressed. Stable electrical properties after either being placed for weeks or continuously prolonged bias stressing for hours in ambient air are achieved for all solution processed unencapsulated OFETs with the channel being exposed to the ambient air for analyte detection. The fabricated device presents a steep subthreshold swing less than 100 mV/decade, and an ON/OFF ratio of 10(6) at a voltage swing of 3 V. The low voltage and stable operation allows the sensor made of the OFET to be incorporated into a battery-powered electronic system for continuously reliable sensing of ammonia vapor in ambient air with very small power consumption of about 50 nW. PMID- 26861404 TI - The Role of Gammaherpesviruses in Cancer Pathogenesis. AB - Worldwide, one fifth of cancers in the population are associated with viral infections. Among them, gammaherpesvirus, specifically HHV4 (EBV) and HHV8 (KSHV), are two oncogenic viral agents associated with a large number of human malignancies. In this review, we summarize the current understanding of the molecular mechanisms related to EBV and KSHV infection and their ability to induce cellular transformation. We describe their strategies for manipulating major cellular systems through the utilization of cell cycle, apoptosis, immune modulation, epigenetic modification, and altered signal transduction pathways, including NF-kB, Notch, Wnt, MAPK, TLR, etc. We also discuss the important EBV latent antigens, namely EBNA1, EBNA2, EBNA3's and LMP's, which are important for targeting these major cellular pathways. KSHV infection progresses through the engagement of the activities of the major latent proteins LANA, v-FLIP and v Cyclin, and the lytic replication and transcription activator (RTA). This review is a current, comprehensive approach that describes an in-depth understanding of gammaherpes viral encoded gene manipulation of the host system through targeting important biological processes in viral-associated cancers. PMID- 26861410 TI - Sleep-Wake Regulation and Its Impact on Working Memory Performance: The Role of Adenosine. AB - The sleep-wake cycle is regulated by a fine-tuned interplay between sleep homeostatic and circadian mechanisms. Compelling evidence suggests that adenosine plays an important role in mediating the increase of homeostatic sleep pressure during time spent awake and its decrease during sleep. Here, we summarize evidence that adenosinergic mechanisms regulate not only the dynamic of sleep pressure, but are also implicated in the interaction of homeostatic and circadian processes. We review how this interaction becomes evident at several levels, including electrophysiological data, neuroimaging studies and behavioral observations. Regarding complex human behavior, we particularly focus on sleep wake regulatory influences on working memory performance and underlying brain activity, with a specific emphasis on the role of adenosine in this interplay. We conclude that a change in adenosinergic mechanisms, whether exogenous or endogenous, does not only impact on sleep-homeostatic processes, but also interferes with the circadian timing system. PMID- 26861413 TI - Identification of a nucleotide in 5' untranslated region contributing to virus replication and virulence of Coxsackievirus A16. AB - Coxsackievirus A16 (CA16) and enterovirus 71 (EV71) are two main causative pathogens of hand, foot and mouth disease (HFMD). Unlike EV71, virulence determinants of CA16, particularly within 5' untranslated region (5'UTR), have not been investigated until now. Here, a series of nucleotides present in 5'UTR of lethal but not in non-lethal CA16 strains were screened by aligning nucleotide sequences of lethal circulating Changchun CA16 and the prototype G10 as well as non-lethal SHZH05 strains. A representative infectious clone based on a lethal Changchun024 sequence and infectious mutants with various nucleotide alterations in 5'UTR were constructed and further investigated by assessing virus replication in vitro and virulence in neonatal mice. Compared to the lethal infectious clone, the M2 mutant with a change from cytosine to uracil at nucleotide 104 showed weaker virulence and lower replication capacity. The predicted secondary structure of the 5'UTR of CA16 RNA showed that M2 mutant located between the cloverleaf and stem-loop II, affected interactions between the 5'UTR and the heterogeneous nuclear ribonucleoprotein K (hnRNP K) and A1 (hnRNP A1) that are important for translational activity. Thus, our research determined a virulence associated site in the 5'UTR of CA16, providing a crucial molecular target for antiviral drug development. PMID- 26861415 TI - A comprehensive framework for functional diversity patterns of marine chromophytic phytoplankton using rbcL phylogeny. AB - Marine chromophytes are taxonomically diverse group of algae and contribute approximately half of the total oceanic primary production. To understand the global patterns of functional diversity of chromophytic phytoplankton, robust bioinformatics and statistical analyses including deep phylogeny based on 2476 form ID rbcL gene sequences representing seven ecologically significant oceanographic ecoregions were undertaken. In addition, 12 form ID rbcL clone libraries were generated and analyzed (148 sequences) from Sundarbans Biosphere Reserve representing the world's largest mangrove ecosystem as part of this study. Global phylogenetic analyses recovered 11 major clades of chromophytic phytoplankton in varying proportions with several novel rbcL sequences in each of the seven targeted ecoregions. Majority of OTUs was found to be exclusive to each ecoregion, whereas some were shared by two or more ecoregions based on beta diversity analysis. Present phylogenetic and bioinformatics analyses provide a strong statistical support for the hypothesis that different oceanographic regimes harbor distinct and coherent groups of chromophytic phytoplankton. It has been also shown as part of this study that varying natural selection pressure on form ID rbcL gene under different environmental conditions could lead to functional differences and overall fitness of chromophytic phytoplankton populations. PMID- 26861414 TI - Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns. AB - Folate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina's HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2, GRM8, SLC16A12, OPCML, PRPH, LHX1, KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring. PMID- 26861416 TI - Detecting Change over Time: A Comparison of the SLUMS Examination and the MMSE in Older Adults at Risk for Cognitive Decline. AB - AIMS: To directly compare the 1-year stability of Mini-Mental State Examination (MMSE) score and Saint Louis University Mental Status (SLUMS) examination score and correlate score changes with demographic variables, clinical factors, and functional domains. METHODS: A sample of 304 study participants was recruited from residential and clinical settings in Ohio. Follow-up assessments were administered after 1 year with a retention rate of 92% (n = 281). Functional domains included the Instrumental Activities of Daily Living (IADL) scale. RESULTS: MMSE and SLUMS scores correlated with each other (r = 0.65, P < 0.001) and with two functional measures, including the IADL (r = 0.27, r = 0.24, P < 0.001). However, the MMSE and SLUMS frequently placed the same subject into different categories. Rates of reversion and conversion varied between the two tests. The 1-year changes in MMSE raw score correlated with changes in three functional domains as well as age (P < 0.05), while SLUMS raw score changes did not correlate with any functional measures. CONCLUSION: Our large, longitudinal data set allowed us to compare the tests' stability, which differed between the SLUMS and MMSE. The MMSE may be more sensitive than the SLUMS to 1-year cognitive changes influencing functional abilities. PMID- 26861417 TI - A Multicenter Pragmatic Interrupted Time Series Analysis of Chlorhexidine Gluconate Bathing in Community Hospital Intensive Care Units. AB - OBJECTIVE To determine whether daily chlorhexidine gluconate (CHG) bathing of intensive care unit (ICU) patients leads to a decrease in hospital-acquired infections (HAIs), particularly infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). DESIGN Interrupted time series analysis. SETTING The study included 33 community hospitals participating in the Duke Infection Control Outreach Network from January 2008 through December 2013. PARTICIPANTS All ICU patients at study hospitals during the study period. METHODS Of the 33 hospitals, 17 hospitals implemented CHG bathing during the study period, and 16 hospitals that did not perform CHG bathing served as controls. Primary pre-specified outcomes included ICU central-line-associated bloodstream infections (CLABSIs), primary bloodstream infections (BSI), ventilator-associated pneumonia (VAP), and catheter-associated urinary tract infections (CAUTIs). MRSA and VRE HAIs were also evaluated. RESULTS Chlorhexidine gluconate (CHG) bathing was associated with a significant downward trend in incidence rates of ICU CLABSI (incidence rate ratio [IRR], 0.96; 95% confidence interval [CI], 0.93-0.99), ICU primary BSI (IRR, 0.96; 95% CI, 0.94 0.99), VRE CLABSIs (IRR, 0.97; 95% CI, 0.97-0.98), and all combined VRE infections (IRR, 0.96; 95% CI, 0.93-1.00). No significant trend in MRSA infection incidence rates was identified prior to or following the implementation of CHG bathing. CONCLUSIONS In this multicenter, real-world analysis of the impact of CHG bathing, hospitals that implemented CHG bathing attained a decrease in ICU CLABSIs, ICU primary BSIs, and VRE CLABSIs. CHG bathing did not affect rates of specific or overall infections due to MRSA. Our findings support daily CHG bathing of ICU patients. Infect Control Hosp Epidemiol 2016;37:791-797. PMID- 26861418 TI - NMDA and non-NMDA glutamate receptors in the paraventricular nucleus of the hypothalamus modulate different stages of hemorrhage-evoked cardiovascular responses in rats. AB - Here we report the involvement of N-Methyl-d-Aspartate (NMDA) and non-NMDA glutamate receptors from the paraventricular nucleus of the hypothalamus (PVN) in the mediation of cardiovascular changes observed during hemorrhage and post bleeding periods. In addition, the present study provides further evidence of the involvement of circulating vasopressin and cardiac sympathetic activity in cardiovascular responses to hemorrhage. Systemic treatment with the V1 vasopressin receptor antagonist dTyr(CH2)5(Me)AVP (50 MUg/kg, i.v.) increased the latency to the onset of hypotension during hemorrhage and slowed post-bleeding recovery of blood pressure. Systemic treatment with the beta1-adrenergic receptor antagonist atenolol (1 mg/kg, i.v.) also increased the latency to the onset of hypotension during hemorrhage. Moreover, atenolol reversed the hemorrhage-induced tachycardia into bradycardia. Bilateral microinjection of the selective NMDA glutamate receptor antagonist LY235959 (2 nmol/100 nL) into the PVN blocked the hypotensive response to hemorrhage and reduced the tachycardia during the post hemorrhage period. Systemic treatment with dTyr(CH2)5(Me)AVP inhibited the effect of LY235959 on hemorrhage-induced hypotension, without affecting the post bleeding tachycardia. PVN treatment with the selective non-NMDA receptor antagonist NBQX (2 nmol/100 nL) reduced the recovery of blood pressure to normal levels in the post-bleeding phase and reduced hemorrhage-induced tachycardia. Combined blockade of both NMDA and non-NMDA glutamate receptors in the PVN completely abolished the hypotensive response in the hemorrhage period and reduced the tachycardiac response in the post-hemorrhage period. These results indicate that local PVN glutamate neurotransmission is involved in the neural pathway mediating cardiovascular responses to hemorrhage, via an integrated control involving autonomic nervous system activity and vasopressin release into the circulation. PMID- 26861420 TI - Continuing Medical Education III: MOC, CME, ABD, ABMS, ACGME, CMS, FSMB, IOM, MOL, PQRS, SMB, Etcetera et Ad Nauseum, Revisited. PMID- 26861421 TI - Tungiasis: A Neglected Disease Related to Poverty. PMID- 26861422 TI - Annular Elastolytic Giant Cell Granuloma and Temporal Arteritis Following Herpes Zoster. PMID- 26861423 TI - On Zosteriform Distribution. PMID- 26861424 TI - Zosteriform Staphylococcus aureus Cutaneous Infection: Report of Two Patients With Dermatomal Bacterial Infection. AB - The aim of this study was to describe cutaneous infections, which are zosteriform in distribution, including two patients with dermatomal Staphylococcus aureus infection. Herpes zoster infectious lesions usually occur in a dermatomal distribution. Other viruses, such as herpes simplex virus, can also appear with zosteriform lesions and closely mimic the clinical presentation of herpes zoster. Additionally, other skin infections, less commonly, are zosteriform. Two patients who developed zosteriform S aureus skin infection are described. A medical literature search for zosteriform dermatomal infections yielded other cutaneous infections with a zosteriform presentation. Two patients had S aureus and methicillin-resistant S aureus infection with skin lesions occupying the T11-T12 dermatomes and the T4 dermatome, respectively. They responded to antibacterial agents and adjuvant therapy. Patients with viral, fungal, and spirochete zosteriform infections are summarized. In addition to varicella-zoster virus infection, zosteriform skin infection can occur with viral (varicella-zoster virus, herpes simplex virus, and Epstein-Barr virus), superficial (dermatophyte), and deep (phaeohyphomycosis and zygomycosis) fungal, and bacterial (S aureus and methicillin-resistant S aureus) infections. These infections should be considered in the differential diagnosis of a zosteriform infection that does not present with the classic clinical picture for herpes zoster or that does not respond to standard treatments for varicellazoster virus. PMID- 26861425 TI - Treatment of Scabies: Comparison of Lindane 1% vs Permethrin 5. AB - Scabies, whose etiologic agent is Sarcoptes scabiei, is a neglected parasitic disease that is a major public health problem in many resourcepoor regions. Its current therapies include benzyl benzoate, lindane, permethrin, sulfur, crotamiton, monosulfiram, and oral ivermectin. The aim of this study was to compare the efficacy and safety of lindane 1% lotion vs permethrin 5% in the treatment of scabies. A total of 120 patients with scabies attending a dermatology outpatient department were included. Patients were randomly divided into two groups. Sixty patients and their family contacts received 5% permethrin cream and the other 60 received 1% lindane lotion. Treatment was evaluated at intervals of 2 and 4 weeks. Permethrin provided improvement in 48 patients (80%) after 2 weeks, whereas lindane was effective in only 28 patients (46.6%). Permethrin (5%) cream was found to be significantly more effective in the treatment of scabies compared with lindane in this study. Adverse effects were rare in both the permethrin and lindane groups. PMID- 26861419 TI - In synch but not in step: Circadian clock circuits regulating plasticity in daily rhythms. AB - The suprachiasmatic nucleus (SCN) is a network of neural oscillators that program daily rhythms in mammalian behavior and physiology. Over the last decade much has been learned about how SCN clock neurons coordinate together in time and space to form a cohesive population. Despite this insight, much remains unknown about how SCN neurons communicate with one another to produce emergent properties of the network. Here we review the current understanding of communication among SCN clock cells and highlight a collection of formal assays where changes in SCN interactions provide for plasticity in the waveform of circadian rhythms in behavior. Future studies that pair analytical behavioral assays with modern neuroscience techniques have the potential to provide deeper insight into SCN circuit mechanisms. PMID- 26861426 TI - Actinic Prurigo. AB - Actinic prurigo is an idiopathic photodermatosis that affects the skin, as well as the labial and conjunctival mucosa in indigenous and mestizo populations of Latin America. It starts predominantly in childhood, has a chronic course, and is exacerbated with solar exposure. Little is known of its pathophysiology, including the known mechanisms of the participation of HLA-DR4 and an abnormal immunologic response with increase of T CD4+ lymphocytes. The presence of IgE, eosinophils, and mast cells suggests that it is a hypersensitivity reaction (likely type IVa or b). The diagnosis is clinical, and the presence of lymphoid follicles in the mucosal histopathologic study of mucosa is pathognomonic. The best available treatment to date is thalidomide, despite its secondary effects. PMID- 26861428 TI - Oral Mucosal Lesions: Oral Cavity Biology-Part I. AB - It is important to evaluate the background of oral cavity biology to define morphologic abrasions in oral mucosa following a host of local and/ or systemic disorders. The oral cavity is not only the beginning of the digestive system, but it also plays a significant role in communication; the voice (although the voice is produced in the throat), tongue, lips, and jaw are its essential components to produce the range of sounds. The vestibule and the oral cavity are its major parts, and are usually moist. The lips and the teeth are in approximation, marking its start up. The anatomy of the oral cavity in brief has been reviewed in right prospective for disease related changed morphology, thus facilitating interpretation. PMID- 26861429 TI - What Lies Beneath: The Importance of Proper Diagnosis of Cutaneous Horn. PMID- 26861430 TI - COSENTYX (Secukinumab). PMID- 26861431 TI - Dermatofibromas: From "Ho-Hum" to "OMG!". PMID- 26861432 TI - Suppuration Following Hair Implantation. PMID- 26861433 TI - Twenty-Nail Dystrophy and Darier's (Darier-White) Disease. AB - A 35-year-old married man presented with progressive distortion of all the nails of the hands and toes for the past 30 years. Initially, his parents noticed yellowish discoloration and roughness of the thumb nail at the age of 5 years. Since then, the changes have been insidious to involve the other nails. Currently, the nails are lusterless, rough, ridged, and difficult to trim. In addition, the patient has had dark, dirty-looking raised eruptions over the skin, attended by generalized itching, corresponding to the onset of the nail lesions. His mother experienced similar disease. Examination of the nails was marked by alternating elevation and depression (ridging) and/or pitting, lack of luster, roughening, sandpaper texture, and splitting, along with muddy, grayish white discoloration. Dystrophy of the nails was prominent. The changes were bilateral and symmetrical, affecting all 10 fingers and 10 toes (Figure 1). PMID- 26861434 TI - Chlorambucil-Induced Radiation Recall Dermatitis. AB - A 65-year-old woman was diagnosed with low-grade non-Hodgkin lymphoma (Figure 1). She was treated with six cycles of cyclophosphamide, hydroxydaunorubicin, oncovin (vincristine), and prednisolone (CHOP) and three cycles of fludarabine and mitoxantrone. Ten months later she received radiotherapy to the left groin (total dose of 50 Gy in 25 fractions over 5 weeks) without complications. PMID- 26861435 TI - Annular Elastolytic Giant Cell Granuloma and Temporal Arteritis Following Herpes Zoster. AB - A 70-year-old woman, who presented with pain and functional limitation of her right shoulder, without any previous traumatic incident, was evaluated in an emergency department. A shoulder x-ray was performed, and she received an intrajoint injection of an unspecified amount of triamcinolone. Forty-eight hours later, she noticed a papulovesicular and bullous eruption with a dermatomal distribution on her nape, supraclavicle, and left brachial and antebrachial regions (T1-T2-C5-C6-8). A diagnosis of herpes zoster (HZ) was made, for which she received valacyclovir 1 g every 8 hours for 10 days, pregabalin 75 mg every 8 hours, and topical acyclovir, with good response. The lesions and pain subsided, and results from general laboratory tests were normal or negative. PMID- 26861436 TI - Basal Cell Carcinoma in a Patient With Brooke-Spiegler Syndrome. AB - A 46-year-old woman was diagnosed with Brooke-Spiegler syndrome (BSS) with lesions on her head, predominantly on the center of her face, auricles, and scalp. The facial lesions were polymorphic, pale, confluent, skin-colored, and papular, whereas the scalpel lesions appeared as erythematous and violet lumps that varied in size (Figure 1A, B). PMID- 26861437 TI - Cutaneous Necrotic Papule as Invasive Aspergillosis in a Heart Transplant Patient. AB - A 46-year-old African American man presented with a 3- to 4-day history of a new painful lesion on his left lower extremity. Other reported symptoms included a productive cough and chest pain; the patient denied fever and chills. His medical history was significant for a heart transplant 4 months prior to presentation followed by transplant rejection 2 weeks after the transplant. Medications included an antirejection/immunosuppressive regimen consisting of prednisone, tacrolimus, mycophenolate mofetil, and prophylaxis treatment with valganciclovir and trimethoprim-sulfamethoxazole. PMID- 26861438 TI - Benign Eccrine Tumors Presenting on the Penis: Common Tumors at an Uncommon Site. AB - Case 1 A 60-year-old Chinese man presented to the dermatology clinic with an asymptomatic, 0.5 * 0.5-cm erythematous papule on the penile shaft for a 2-year duration (Figure 1a). His medical problems consisted only of well-controlled hypothyroidism and hypertension. The initial clinical diagnoses considered were pyogenic granuloma or condyloma accuminatum. The excisional biopsy revealed a polypoidal lesion entirely covered by epidermis, with a proliferation of cuboidal, basaloid cells, consistent with an eccrine poroma (Figure 1b). Case 2 A 28-year-old Chinese man presented with an asymptomatic fusiform, 1.4 * 0.4-cm nodule over the ventral aspect of the prepuce, for a 10-year duration (Figure 2a). His medical history was otherwise unremarkable. Lymphangioma was the initial clinical diagnosis but biopsy results revealed large collapsed cystic spaces within the superficial dermis lined by a double layer of epithelial cells with eosinophilic cytoplasm, without evidence of decapitation secretion, consistent with an eccrine hidrocystoma (Figure 2b). PMID- 26861440 TI - Galderma Product Line Expands as Promised by President Todd Zavodnick. PMID- 26861441 TI - Correction: Anonymous Dermatopathologists: A Socioeconomic Solution to a Medical Problem. PMID- 26861442 TI - Constant B cell lymphocytosis since early age in a patient with CARD11 mutation: A 20-year follow-up. PMID- 26861443 TI - Liminality in Pediatric Palliative Care. AB - Palliative care for infants, children, and adolescents encompasses numerous transitions and thresholds of uncertainty that challenge conventional clinical medicine. Palliative care clinicians have opportunities to be more comfortable amid such challenges, or perhaps even overcome them, if they are attuned to the unique times and places in which patients, their families, and caregivers find themselves throughout illness and recovery or transitioning toward the end of life. Patient-clinician encounters often dwell in these liminal places. The concept of liminality gives validation to the patient or family's being "stuck in places betwixt and between" a past life rich with relationship and purpose and an acute, chronic, or critical illness. Or having resolved the acute crisis of hospitalization that place between the past bounds of illness and the uncertain path forward, perhaps even toward death. Liminality provides a framework for addressing the unbound spaces that patients and families occupy: What is past is behind-the present place is tenuous and temporary, and what is ahead uncertain. This place is where palliative care clinicians can offer clinicians and families guidance. PMID- 26861444 TI - Comparison of indoor contact time data in Zambia and Western Cape, South Africa suggests targeting of interventions to reduce Mycobacterium tuberculosis transmission should be informed by local data. AB - BACKGROUND: In high incidence settings, the majority of Mycobacterium tuberculosis (M.tb) transmission occurs outside the household. Little is known about where people's indoor contacts occur outside the household, and how this differs between different settings. We estimate the number of contact hours that occur between adults and adult/youths and children in different building types in urban areas in Western Cape, South Africa, and Zambia. METHODS: Data were collected from 3206 adults using a cross-sectional survey, on buildings visited in a 24-h period, including building function, visit duration, and number of adults/youths and children (5-12 years) present. The mean numbers of contact hours per day by building function were calculated. RESULTS: Adults in Western Cape were more likely to visit workplaces, and less likely to visit shops and churches than adults in Zambia. Adults in Western Cape spent longer per visit in other homes and workplaces than adults in Zambia. More adults/youths were present at visits to shops and churches in Western Cape than in Zambia, and fewer at homes and hairdressers. More children were present at visits to shops in Western Cape than in Zambia, and fewer at schools and hairdressers. Overall numbers of adult/youth indoor contact hours were the same at both sites (35.4 and 37.6 h in Western Cape and Zambia respectively, p = 0.4). Child contact hours were higher in Zambia (16.0 vs 13.7 h, p = 0.03). Adult/youth and child contact hours were highest in workplaces in Western Cape and churches in Zambia. Compared to Zambia, adult contact hours in Western Cape were higher in workplaces (15.2 vs 8.0 h, p = 0.004), and lower in churches (3.7 vs 8.6 h, p = 0.002). Child contact hours were higher in other peoples' homes (2.8 vs 1.6 h, p = 0.03) and workplaces (4.9 vs 2.1 h, p = 0.003), and lower in churches (2.5 vs 6.2, p = 0.004) and schools (0.4 vs 1.5, p = 0.01). CONCLUSIONS: Patterns of indoor contact between adults and adults/youths and children differ between different sites in high M.tb incidence areas. Targeting public buildings with interventions to reduce M.tb transmission (e.g. increasing ventilation or UV irradiation) should be informed by local data. PMID- 26861445 TI - The association between BMI development among young children and (un)healthy food choices in response to food advertisements: a longitudinal study. AB - BACKGROUND: Previous studies have focused on the acute effects of food advertisements on the caloric intake of children; however, the long-term effects of this food cue reactivity on weight gain have not been examined. The main aim of this study was to explore if reactivity to food cues in an advertisement was associated with weight status two years later. METHODS: Children wo had previously taken part in an experiment investigating the impact of advergames on food intake had their height and weight re-measured two years later, for assessment of body mass index (BMI). A within-subject design was used to test the associations between food choices and BMI over time. In the previous experiment, children played an advergame that promoted energy-dense snacks, fruit, or nonfood products, or did not play an advergame (control condition). After playing the game, the free intake of energy-dense snacks and fruits was measured. RESULTS: Children who ate more apple after playing an advergame promoting energy-dense snacks had a lower BMI two years later. Consumption of energy-dense snacks after playing an advergame promoting energy-dense snacks was not associated with BMI two years later. In other condition, no association was found between food intake and BMI after two years . CONCLUSIONS: The findings suggest that coping with environmental cues that trigger unhealthy eating behavior is associated with the body mass index of young children two years later. This might imply that learning to respond to food cues by choosing healthy options might prevent children from excessive weight gain. This trial was registered at as ISRCTN17013832 . PMID- 26861447 TI - Bipolar vs. borderline - diagnosis is prognosis once again. PMID- 26861448 TI - Simultaneous robotic-assisted adrenalectomy and partial nephrectomy: technical aspects. AB - Robot-assisted partial nephrectomy has become a safe and feasible procedure for small renal masses (SRM). Similarly, robot-assisted adrenalectomy has also been well established. Robotic surgery has provided the possibility to manage complex cases that are considered technically challenging for traditional laparoscopy. We describe in this video the details of performing simultaneous robotic adrenalectomy with partial nephrectomy highlighting the technical aspects of the same. A 62-year-old gentleman presented to us with incidentally detected left renal complex cyst (Bosniak IIF) and a concomitant left adrenal mass. Hormonal evaluation of adrenal tumor revealed raised levels of serum estrogen and DHEAS. A robotic-assisted simultaneous procedure was planned. Patient was positioned in right lateral position. After port placement, robot was brought from the shoulder of the patient and docked. We first excised the adrenal tumor followed by the renal cyst. Total operative time was 180 min with warm ischemia time of 20 min for renal cyst excision. Drain was removed on post-operative day 2. Patient was discharged on post-operative day 3. Histopathology revealed adrenocortical adenoma and benign hemorrhagic renal cyst. We found simultaneous ipsilateral adrenalectomy with partial nephrectomy using robotic assistance is feasible and safe with minimal morbidity. Port placement in such cases should be individualized according to the location of the SRM. The robot provides the ergonomic advantage and 3D vision for better anatomic definition as compared to laparoscopy. PMID- 26861446 TI - Metformin improves the angiogenic potential of human CD34+ cells co-incident with downregulating CXCL10 and TIMP1 gene expression and increasing VEGFA under hyperglycemia and hypoxia within a therapeutic window for myocardial infarction. AB - BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with diabetes mellitus (DM). To identify the most effective treatment for CVD, it is paramount to understand the mechanism behind cardioprotective therapies. Although metformin has been shown to reduce CVD in Type-2 DM clinical trials, the underlying mechanism remains unexplored. CD34(+) cell-based therapies offer a new treatment approach to CVD. The aim of this study was to investigate the effect of metformin on the angiogenic properties of CD34(+) cells under conditions mimicking acute myocardial infarction in diabetes. METHODS: CD34(+) cells were cultured in 5.5 or 16.5 mmol/L glucose +/- 0.01 mmol/L metformin and then additionally +/- 4 % hypoxia. The paracrine function of CD34(+) cell-derived conditioned medium was assessed by measuring pro inflammatory cytokines, vascular endothelial growth factor A (VEGFA), and using an in vitro tube formation assay for angiogenesis. Also, mRNA of CD34(+) cells was assayed by microarray and genes of interest were validated by qRT-PCR. RESULTS: Metformin increased in vitro angiogenesis under hyperglycemia-hypoxia and augmented the expression of VEGFA. It also reduced the angiogenic-inhibitors, chemokine (C-X-C motif) ligand 10 (CXCL10) and tissue inhibitor of metalloproteinase 1 (TIMP1) mRNAs, which were upregulated under hyperglycemia hypoxia. In addition metformin, increased expression of STEAP family member 4 (STEAP4) under euglycemia, indicating an anti-inflammatory effect. CONCLUSIONS: Metformin has a dual effect by simultaneously increasing VEGFA and reducing CXCL10 and TIMP1 in CD34(+) cells in a model of the diabetic state combined with hypoxia. Therefore, these angiogenic inhibitors are promising therapeutic targets for CVD in diabetic patients. Moreover, our data are commensurate with a vascular protective effect of metformin and add to the understanding of underlying mechanisms. PMID- 26861449 TI - Robotic surgery for treatment of chyluria. AB - Chyle is a milky lymphatic fluid that is normally formed in the small intestine to aid in the absorption of dietary fats. Occasionally, chyle leaks into the kidney, ureter, or bladder, which results in chyluria. Chyluria is most commonly caused by the parasite Wuchereria bancrofti and is therefore extremely rare in the USA. The use of robotic surgery for treatment has been suggested as a viable option, but has not been thoroughly reported in the literature. This article reviews the literature on the various treatment options for chyluria and presents the case of a 75-year-old Indian female from the USA who was diagnosed with non parasitic, persistent chyluria and treated with right robotic ureterolysis, renal hilar dissection and intraperitonealization of the ureter. PMID- 26861450 TI - Race effects on pathological and functional outcomes after robotic partial nephrectomy in a single academic tertiary care center. AB - To explore the potential effects of race on pathological outcomes of renal tumor and on kidney function preservation in the patients undergoing robotic partial nephrectomy (RPN) at our center. Retrospective review of our institutional review board approved database for African-American (AA) patients undergoing RPN from 2006 to 2014 was performed. AA and non-AA groups were compared with regards to demographics, tumor characteristics, functional data and, oncological outcomes. For functional outcomes, groups were matched (1:1) in terms of age, preoperative estimated glomerular filtration rate (eGFR) and R.E.N.A.L score. From the total of 1005 patients, 84 were AA. Age and the tumor size were comparable between the two groups (2.7 vs. 3 cm; p = 0.29). Proportion of patients with papillary RCC was higher among AAs compared to non-AAs (43.3 vs. 19.4 %; p < 0.001). After matching AA patients with non-AA counterparts (1:1 matching), eGFR preservation at latest follow up after surgery was comparable between groups (84.3 vs. 85 %; p = 0.25). AA race (OR 3.62, p < 0.001), male gender (OR 2.05, p < 0.001) and low preoperative eGFR (OR 0.97, p < 0.001) were predictors of papillary RCC on multivariate analyses. The incidence of papillary RCC is higher in AA patients undergoing RPN. There was no difference in kidney function recovery after robotic partial nephrectomy in both AA and non-AA groups. AA race itself is not a significant factor in determining renal malignancy. Further studies are needed to clarify the impact of higher prevalence of papillary tumors in AA group in terms of long-term oncological and functional outcomes. PMID- 26861451 TI - A review of job-exposure matrix methodology for application to workers exposed to radiation from internally deposited plutonium or other radioactive materials. AB - Any potential health effects of radiation emitted from radionuclides deposited in the bodies of workers exposed to radioactive materials can be directly investigated through epidemiological studies. However, estimates of radionuclide exposure and consequent tissue-specific doses, particularly for early workers for whom monitoring was relatively crude but exposures tended to be highest, can be uncertain, limiting the accuracy of risk estimates. We review the use of job exposure matrices (JEMs) in peer-reviewed epidemiological and exposure assessment studies of nuclear industry workers exposed to radioactive materials as a method for addressing gaps in exposure data, and discuss methodology and comparability between studies. We identified nine studies of nuclear worker cohorts in France, Russia, the USA and the UK that had incorporated JEMs in their exposure assessments. All these JEMs were study or cohort-specific, and although broadly comparable methodologies were used in their construction, this is insufficient to enable the transfer of any one JEM to another study. Moreover there was often inadequate detail on whether, or how, JEMs were validated. JEMs have become more detailed and more quantitative, and this trend may eventually enable better comparison across, and the pooling of, studies. We conclude that JEMs have been shown to be a valuable exposure assessment methodology for imputation of missing exposure data for nuclear worker cohorts with data not missing at random. The next step forward for direct comparison or pooled analysis of complete cohorts would be the use of transparent and transferable methods. PMID- 26861452 TI - Work, eat and sleep: towards a healthy ageing at work program offshore. AB - BACKGROUND: Health management tools need to be developed to foster healthy ageing at work and sustain employability of ageing work-forces. The objectives of this study were to 1) perform a needs assessment to identify the needs of offshore workers in the Dutch Continental Shelf with regard to healthy ageing at work and 2) to define suitable program objectives for a future healthy ageing at work program in the offshore working population. METHODS: A mixed methods design was used applying an intervention mapping procedure. Qualitative data were gathered in N = 19 semi-structured interviews and six focus-group sessions (N = 49). Qualitative data were used to develop a questionnaire, which was administered among N = 450 offshore workers. Subgroup analyses were performed to investigate age-related differences relating to health status and work-related factors. RESULTS: The importance of good working environments, food, as well as sleep/fatigue management was identified by the qualitative data analysis. A total of 260 offshore workers completed the questionnaire. Significant differences in work ability were found between offshore workers aged <45 and 45-54 years (mean 8.63 vs. 8.19; p = 0.005) and offshore workers aged <45 and >55 years (mean 8.63 vs. 8.22; p = 0.028). Offshore workers had a high BMI (M = 27.06, SD = 3.67), with 46 % classified as overweight (BMI 25-30) and 21 % classified as obese (BMI >30). A significant difference in BMI was found between offshore workers aged <45 and >=55 years (mean 26.3 vs. 28.6; p <0.001). In total, 73 % of offshore workers reported prolonged fatigue. A significant difference in fatigue scores was found between offshore workers aged <45 and >=55 years (mean 36.0 vs. 37.6; p = 0.024). Further, a "dip" was reported by 41 % of offshore workers. Dips were mainly experienced at day 10 or 11 (60 %), with 45 % experiencing the dip both as physical and mental fatigue, whereas 39 % experienced the dip as only mental fatigue. CONCLUSIONS: Both qualitative and quantitative analyses identified work, food and sleep/fatigue management as most important program objectives for a healthy ageing at work and sustainable employability program offshore. Future studies should investigate possible causes of dip occurrences and high fatigue scores to identify suitable interventions. PMID- 26861453 TI - Anticipating missing reference standard data when planning diagnostic accuracy studies. PMID- 26861454 TI - Olfactory Receptor Family 7 Subfamily C Member 1 Is a Novel Marker of Colon Cancer-Initiating Cells and Is a Potent Target of Immunotherapy. AB - PURPOSE: Cancer-initiating cells (CICs) are thought to be essential for tumor maintenance, recurrence, and distant metastasis, and they are therefore reasonable targets for cancer therapy. Cancer immunotherapy is a novel approach to target cancer. In this study, we aimed to establish novel CIC-targeting immunotherapy. EXPERIMENTAL DESIGN: Colorectal cancer (CRC) CICs were isolated as side population (SP) cells. The gene expression profile of CRC CICs was analyzed by cDNA microarray and RT-PCR. Protein expression of olfactory receptor family 7 subfamily C member 1 (OR7C1) were analyzed by Western blot and immunohistochemical staining. The functions of OR7C1 were analyzed by gene overexpression and gene knockdown using siRNAs. OR7C1-positive cells were isolated by a flow cytometer and analyzed. CTLs specific for OR7C1 peptide were generated, and the antitumor effect was addressed by mice adoptive transfer model. RESULTS: OR7C1 has essential roles in the maintenance of colon CICs, and the OR7C1-positive population showed higher tumorigenicity than that of the OR7C1 negative population, indicating that OR7C1 is a novel functional marker for colon CIC. Immunohistochemical staining revealed that OR7C1 high expression was correlated with poorer prognosis in CRC patients. OR7C1-derived antigenic peptide specific CTLs showed specific cytotoxicity for CICs, and an OR7C1-specific CTL clone showed a greater antitumor effect than did a CTL clone targeting all cancer cells in a CTL adoptive transfer mouse model. CONCLUSIONS: OR7C1 is a novel marker for colon CICs and can be a target of potent CIC-targeting immunotherapy. Clin Cancer Res; 22(13); 3298-309. (c)2016 AACR. PMID- 26861456 TI - Impact of Two Measures of Micrometastatic Disease on Clinical Outcomes in Patients with Newly Diagnosed Ewing Sarcoma: A Report from the Children's Oncology Group. AB - PURPOSE: Flow cytometry and RT-PCR can detect occult Ewing sarcoma cells in the blood and bone marrow. These techniques were used to evaluate the prognostic significance of micrometastatic disease in Ewing sarcoma. EXPERIMENTAL DESIGN: Newly diagnosed patients with Ewing sarcoma were enrolled on two prospective multicenter studies. In the flow cytometry cohort, patients were defined as "positive" for bone marrow micrometastatic disease if their CD99(+)/CD45(-) values were above the upper limit in 22 control patients. In the PCR cohort, RT PCR on blood or bone marrow samples classified the patients as "positive" or "negative" for EWSR1/FLI1 translocations. The association between micrometastatic disease burden with clinical features and outcome was assessed. Coexpression of insulin-like growth factor-1 receptor (IGF-1R) on detected tumor cells was performed in a subset of flow cytometry samples. RESULTS: The median total bone marrow CD99(+)CD45(-) percent was 0.0012% (range 0%-1.10%) in the flow cytometry cohort, with 14 of 109 (12.8%) of Ewing sarcoma patients defined as "positive." In the PCR cohort, 19.6% (44/225) patients were "positive" for any EWSR1/FLI1 translocation in blood or bone marrow. There were no differences in baseline clinical features or event-free or overall survival between patients classified as "positive" versus "negative" by either method. CD99(+)CD45(-) cells had significantly higher IGF-1R expression compared with CD45(+) hematopoietic cells (mean geometric mean fluorescence intensity 982.7 vs. 190.9; P < 0.001). CONCLUSIONS: The detection of micrometastatic disease at initial diagnosis by flow cytometry or RT-PCR is not associated with outcome in newly diagnosed patients with Ewing sarcoma. Flow cytometry provides a tool to characterize occult micrometastatic tumor cells for proteins of interest. Clin Cancer Res; 22(14); 3643-50. (c)2016 AACR. PMID- 26861455 TI - PlGF/VEGFR-1 Signaling Promotes Macrophage Polarization and Accelerated Tumor Progression in Obesity. AB - PURPOSE: Obesity promotes pancreatic and breast cancer progression via mechanisms that are poorly understood. Although obesity is associated with increased systemic levels of placental growth factor (PlGF), the role of PlGF in obesity induced tumor progression is not known. PlGF and its receptor VEGFR-1 have been shown to modulate tumor angiogenesis and promote tumor-associated macrophage (TAM) recruitment and activity. Here, we hypothesized that increased activity of PlGF/VEGFR-1 signaling mediates obesity-induced tumor progression by augmenting tumor angiogenesis and TAM recruitment/activity. EXPERIMENTAL DESIGN: We established diet-induced obese mouse models of wild-type C57BL/6, VEGFR-1 tyrosine kinase (TK)-null, or PlGF-null mice, and evaluated the role of PlGF/VEGFR-1 signaling in pancreatic and breast cancer mouse models and in human samples. RESULTS: We found that obesity increased TAM infiltration, tumor growth, and metastasis in pancreatic cancers, without affecting vessel density. Ablation of VEGFR-1 signaling prevented obesity-induced tumor progression and shifted the tumor immune environment toward an antitumor phenotype. Similar findings were observed in a breast cancer model. Obesity was associated with increased systemic PlGF, but not VEGF-A or VEGF-B, in pancreatic and breast cancer patients and in various mouse models of these cancers. Ablation of PlGF phenocopied the effects of VEGFR-1-TK deletion on tumors in obese mice. PlGF/VEGFR-1-TK deletion prevented weight gain in mice fed a high-fat diet, but exacerbated hyperinsulinemia. Addition of metformin not only normalized insulin levels but also enhanced antitumor immunity. CONCLUSIONS: Targeting PlGF/VEGFR-1 signaling reprograms the tumor immune microenvironment and inhibits obesity-induced acceleration of tumor progression. Clin Cancer Res; 22(12); 2993-3004. (c)2016 AACR. PMID- 26861458 TI - A Novel Carcinoembryonic Antigen T-Cell Bispecific Antibody (CEA TCB) for the Treatment of Solid Tumors. AB - PURPOSE: CEA TCB is a novel IgG-based T-cell bispecific (TCB) antibody for the treatment of CEA-expressing solid tumors currently in phase I clinical trials (NCT02324257). Its format incorporates bivalent binding to CEA, a head-to-tail fusion of CEA- and CD3e-binding Fab domains and an engineered Fc region with completely abolished binding to FcgammaRs and C1q. The study provides novel mechanistic insights into the activity and mode of action of CEA TCB. EXPERIMENTAL DESIGN: CEA TCB activity was characterized on 110 cell lines in vitro and in xenograft tumor models in vivo using NOG mice engrafted with human peripheral blood mononuclear cells. RESULTS: Simultaneous binding of CEA TCB to tumor and T cells leads to formation of immunologic synapses, T-cell activation, secretion of cytotoxic granules, and tumor cell lysis. CEA TCB activity strongly correlates with CEA expression, with higher potency observed in highly CEA expressing tumor cells and a threshold of approximately 10,000 CEA-binding sites/cell, which allows distinguishing between high- and low-CEA-expressing tumor and primary epithelial cells, respectively. Genetic factors do not affect CEA TCB activity confirming that CEA expression level is the strongest predictor of CEA TCB activity. In vivo, CEA TCB induces regression of CEA-expressing xenograft tumors with variable amounts of immune cell infiltrate, leads to increased frequency of activated T cells, and converts PD-L1 negative into PD-L1 positive tumors. CONCLUSIONS: CEA TCB is a novel generation TCB displaying potent antitumor activity; it is efficacious in poorly infiltrated tumors where it increases T-cell infiltration and generates a highly inflamed tumor microenvironment. Clin Cancer Res; 22(13); 3286-97. (c)2016 AACR. PMID- 26861457 TI - Clinical Trial of Oral Nelfinavir before and during Radiation Therapy for Advanced Rectal Cancer. AB - PURPOSE: Nelfinavir, a PI3K pathway inhibitor, is a radiosensitizer that increases tumor blood flow in preclinical models. We conducted an early-phase study to demonstrate the safety of nelfinavir combined with hypofractionated radiotherapy (RT) and to develop biomarkers of tumor perfusion and radiosensitization for this combinatorial approach. EXPERIMENTAL DESIGN: Ten patients with T3-4 N0-2 M1 rectal cancer received 7 days of oral nelfinavir (1,250 mg b.i.d.) and a further 7 days of nelfinavir during pelvic RT (25 Gy/5 fractions/7 days). Perfusion CT (p-CT) and DCE-MRI scans were performed pretreatment, after 7 days of nelfinavir and prior to the last fraction of RT. Biopsies taken pretreatment and 7 days after the last fraction of RT were analyzed for tumor cell density (TCD). RESULTS: There were 3 drug-related grade 3 adverse events: diarrhea, rash, and lymphopenia. On DCE-MRI, there was a mean 42% increase in medianKtrans, and a corresponding median 30% increase in mean blood flow on p-CT during RT in combination with nelfinavir. Median TCD decreased from 24.3% at baseline to 9.2% in biopsies taken 7 days after RT (P= 0.01). Overall, 5 of 9 evaluable patients exhibited good tumor regression on MRI assessed by tumor regression grade (mrTRG). CONCLUSIONS: This is the first study to evaluate nelfinavir in combination with RT without concurrent chemotherapy. It has shown that nelfinavir-RT is well tolerated and is associated with increased blood flow to rectal tumors. The efficacy of nelfinavir-RT versus RT alone merits clinical evaluation, including measurement of tumor blood flow. PMID- 26861459 TI - Clinical and Molecular Characteristics of NF1-Mutant Lung Cancer. AB - PURPOSE: NF1 is a tumor suppressor that negatively regulates Ras signaling. NF1 mutations occur in lung cancer, but their clinical significance is unknown. We evaluated clinical and molecular characteristics of NF1 mutant lung cancers with comparison to tumors with KRAS mutations. EXPERIMENTAL DESIGN: Between July 2013 and October 2014, 591 non-small cell lung cancer (NSCLC) tumors underwent targeted next-generation sequencing in a 275 gene panel that evaluates gene mutations and genomic rearrangements. NF1 and KRAS cohorts were identified, with subsequent clinical and genomic analysis. RESULTS: Among 591 patients, 60 had NF1 mutations (10%) and 141 (24%) had KRAS mutations. 15 NF1 mutations (25%) occurred with other oncogenic mutations [BRAF (2); ERBB2 (2); KRAS (9); HRAS (1); NRAS (1)]. There were 72 unique NF1 variants. NF1 tumor pathology was diverse, including both adenocarcinoma (36, 60%) and squamous cell carcinoma (10, 17%). In contrast, KRAS mutations occurred predominantly in adenocarcinoma (136, 96%). Both mutations were common in former/current smokers. Among NF1 tumors without concurrent oncogenic alterations, TP53 mutations/2-copy deletions occurred more often (33, 65%) than with KRAS mutation (46, 35%; P < 0.001). No difference between cohorts was seen with other tumor suppressors. CONCLUSIONS: NF1 mutations define a unique population of NSCLC. NF1 and KRAS mutations present in similar patient populations, but NF1 mutations occur more often with other oncogenic alterations and TP53 mutations. Therapeutic strategies targeting KRAS activation, including inhibitors of MAP kinase signaling, may warrant investigation in NF1 mutant tumors. Tumor-suppressor inactivation patterns may help further define novel treatment strategies. Clin Cancer Res; 22(13); 3148-56. (c)2016 AACR. PMID- 26861460 TI - Reduced Expression of SMAD4 Is Associated with Poor Survival in Colon Cancer. AB - PURPOSE: SMAD4 loss is associated with the development of metastases and poor prognosis. We evaluated expression of SMAD4 protein and its association with tumor characteristics, including biomarkers and outcome in terms of relapse-free survival and overall survival. EXPERIMENTAL DESIGN: We used 1,564 stage II/III colon cancer samples from PETACC-3 to evaluate SMAD4 expression by immunohistochemistry. SMAD4 protein expression was validated by assessing mRNA expression using available expression array data. SMAD4 expression was also studied on 34 adenomas and 10 colon cancer liver metastases with their primaries. Loss of SMAD4 immunoreactivity was defined as focal or diffuse. Cases without SMAD4 loss were subdivided into those with strong and weak expression. RESULTS: SMAD4 protein expression was informative in 1,381/1,564 cases. SMAD4 loss was found in 293/1,381 (21%) cases. Of 1,088 cases without SMAD4 loss (79%), 530 showed weak and 558 strong expression. SMAD4 loss occurred also in adenomas, but less extensively than in carcinomas. Liver metastases followed mostly the expression pattern of the primary tumor. SMAD4 loss, including weak expression, identified patients with poor survival in stage II as well as III and in both treatment arms. SMAD4 loss was less frequent in tumors with microsatellite instability and more frequent in those with loss of heterozygosity of 18q. CONCLUSIONS: We conclude that clonal loss of SMAD4 expression in adenomas, carcinomas, and liver metastases increases with disease progression. SMAD4 loss, and to a lesser extent weak expression, is strongly associated with poor survival regardless of stage. Clin Cancer Res; 22(12); 3037-47. (c)2016 AACR. PMID- 26861461 TI - SIRT6 Overexpression Potentiates Apoptosis Evasion in Hepatocellular Carcinoma via BCL2-Associated X Protein-Dependent Apoptotic Pathway. AB - PURPOSE: To characterize the functional role of SIRT6 in hepatocellular carcinoma (HCC). EXPERIMENTAL DESIGN: The expression of SIRT6 in 60 paired paraffin embedded HCC tissues and adjacent nontumoral liver tissues was examined by immunohistochemistry. The expression of SIRT6 in 101 paired frozen HCC tissues and adjacent nontumoral liver tissues was analyzed by Western blotting analysis and qPCR. The biologic consequences of overexpression and knockdown of SIRT6 in HCC cell lines were studied in vitro and in vivo RESULTS: SIRT6 expression was frequently upregulated in clinical HCC samples, and its expression was highly associated with tumor grade (P = 0.02), tumor size (P = 0.02), vascular invasion (P = 0.004), and shorter survival (P = 0.024). Depletion of SIRT6 from multiple liver cancer cell lines inhibited their growth and induced apoptosis in vitro At the molecular level, we observed that the activation of the BCL2-associated X protein (Bax) signaling pathway, a major pathway that determines cancer cell apoptosis, is regulated by SIRT6 via its deacetylase activity. SIRT6 was recruited to the promoter of Bax, where it deacetylated histone 3 lysine 9 and suppressed its promoter activity. Binding of transcription factors (p53 and E2F 1) to Bax promoter was also generally increased in SIRT6-depleted cells. In mouse xenografts, SIRT6 suppression inhibited tumor growth and induced apoptosis. Finally, there is a negative correlation between SIRT6 and Bax mRNA expressions in human HCC samples. CONCLUSIONS: SIRT6 is an important protumorigenic factor in liver carcinogenesis. Thus, the therapeutic targeting of SIRT6 may offer options for HCC treatment. Clin Cancer Res; 22(13); 3372-82. (c)2016 AACR. PMID- 26861462 TI - Effect of aspirin on models of retinal pigment epithelium pathology. AB - BACKGROUND: To characterize the effect of aspirin (ASA) in mouse models of choroidal neovascularization (CNV) and retinal degeneration. METHODS: In vivo: Male C57BL/6 mice were given ASA in food or regular rodent diet. CNV was induced by argon laser photocoagulation. Subretinal injections of polyethylene glycol 400 (PEG-400) were administered to induce retinal degeneration. CNV size, laser spot area and mean intensity of VEGF in the laser injured zones were measured. In the PEG injected eyes the thickness of retinal pigment epithelium (RPE) and choroid was measured. In vitro: Human ARPE-19 cells were treated with 0.5 or 2.0 mM/L of ASA for 72 h. ELISA was used to measure the concentration of VEGF and CCL-2 in the supernatants. Additionally, damaged RPE monolayer was treated with ASA (0.5 or 2.0 mM/L) and vehicle separately. Size of damaged area was measured. ELISA was used to measure secretion of VEGF-A and CCL-2 by damaged cells after 24 h. RESULTS: No statistically significant effect of ASA on CNV size, laser spot size or VEGF expression was noted in CNV model. In the PEG model, ASA did not have any effect on RPE and choroid thickness; however, a significant increase in RPE atrophy was observed (P = 0.02 + 38%). In addition, ASA had a significant effect on the ability of the RPE cells to regenerate and become confluent after mechanical damage. CONCLUSIONS: ASA at doses consumed clinically for various medical causes may not worsen CNV in human subjects. However, ASA may increase RPE atrophy when consumed over long periods of time. PMID- 26861463 TI - Research consent capacity varies with executive function and memory in Parkinson's disease. AB - BACKGROUND: We examined the association between cognitive domains and research consent capacity in PD. Our hypothesis was that research consent capacity is best predicted by executive function. METHODS: A cohort of 90 PD patients and 30 healthy older adults were administered the MacArthur Competence Assessment Tool for Clinical Research, Dementia Rating Scale-2, and the MoCA. Experts classified patients as either "capable" or "not capable" of providing informed consent to participate in two clinical trials. RESULTS: MacArthur Competence Assessment Tool for Clinical Research Reasoning scores for both clinical trial types were most associated with executive functions and delayed recall. As scores on these domains improved, the odds of an expert rating of "capable of consent" increased. CONCLUSIONS: These results extend our previous findings by demonstrating that memory and executive abilities appear closely associated with capacity when evaluated using either a structured interview or expert judgment of that interview. PMID- 26861464 TI - MRI changes of pelvic floor and pubic bone observed in primiparous women after childbirth by normal vaginal delivery. AB - OBJECTIVE: To identify and characterize changes in the pelvic floor and pubic bone, using magnetic resonance imaging, in primiparous women with normal vaginal delivery, in comparison with nulliparous women. METHODS: Pelvic MR images from ten primiparous women, 6-7 weeks after normal vaginal delivery, and ten nulliparous women were obtained from January to April 2014. The selected women were scanned using a multiplanar T2FRFSE sequence and T2fsFRFSE sequence. Changes in the pelvic floor and pubic bone in primiparous women, including tears of the levator ani fibers, pubic bone edema, and fractures, were assessed on the MR images in comparison with images from normal nulliparous women. Injury to the levator ani was evaluated and scored. The incidence, location and the extent of injury to the levator ani and pubic bone were characterized further. RESULTS: Eight out of ten primiparous women had imaging abnormalities after normal vaginal delivery. Three women had unilateral tears of the pubococcygeus, in which the defect in the muscle was located at or near its origin at the pubic bone, and one had a pubococcygeus tear accompanied by bilateral spilling of the vagina. Four women had partial tears of the iliococcygeus: one was a bilateral tear, and three were unilateral. None had a tear of the coccygeus. Eight women had pubic bone marrow edema; one was accompanied by a pubic bone fracture line. None of the nulliparous women had any abnormality of the pelvic floor and pubic bone. CONCLUSION: Abnormalities of the pelvic floor and pubic bone were observed in primiparous women but not in nulliparous women. In primiparous women, most levator ani muscle tears are at or near the point of origin, and pubococcygeus injuries are usually accompanied by pubic bone marrow edema. PMID- 26861465 TI - Estrogen receptor beta and ovarian cancer: a key to pathogenesis and response to therapy. AB - INTRODUCTION: Ovarian cancer remains the leading cause of mortality due to gynecological tumors. Estrogen receptors (ERs) seem to participate in tumor progression even in the absence of estrogens. Twenty years after the cloning of the second estrogen receptor, a wide spectrum of studies have shown its implication in both physiologic and pathologic pathways. ERbeta, being the predominant type of ER in normal ovary tissue, has not only been linked with pathogenesis of ovarian cancer, but also with response to treatment. Unlike ERalpha, which is primarily linked with cell growth, ERbeta presence is prominent in signaling pathways, cell cycle regulation and apoptosis. METHODS: Literature review of relevant published material (from PubMed, Scopus, and Cochrane databases) was conducted. RESULTS: Polymorphisms in the respective ESR2 gene, epigenetic modifications and isoforms of the receptor have been extensively studied to assess potential correlations with responsiveness to treatment and tumor behavior. Studies on the exact roles of ERbeta and its genetic variations in altering effectiveness and toxicity of ovarian cancer treatment regimens are lacking. CONCLUSION: Clinical utilization of ERbeta actions in the management of ovarian cancer is discussed in an up-to-date review. PMID- 26861466 TI - Robotic assisted hysterectomy in obese patients: a systematic review. AB - OBJECTIVE: Robotic hysterectomy is an alternative approach to the management of female genital tract pathology. METHODS: A systematic literature review was performed to evaluate the till now available literature evidence on robotic assisted hysterectomy in obese and morbidly obese patients. RESULTS: In total, robotic assisted hysterectomy was performed on 2769 patients. The most frequent indication for robotic hysterectomy was endometrial carcinoma (1832 out of 2769 patients, 66.2 %). Hypertension, diabetes mellitus, obstructive sleep apnea, chronic obstructive pulmonary disease and venous thromboembolism were the most common comorbidities reported. The conversion rate to laparotomy was 92 out of 2226 patients (4.1 %). The most frequent intraoperative complications for robotic hysterectomy were gastrointestinal injury (17 out of 2769 patients, 0.6 %), haemorrhage (five out of 2769 patients, 0.2 %) and bladder injury (five out of 2769 patients, 0.2 %). Wound infections/dehiscence (66 out of 2769 patients, 2.4 %), fever (56 out of 2769 patients, 2 %), pulmonary complications (55 out of 2769 patients, 1.9 %), urogenital complications (36 out of 2769 patients, 1.3 %) and postoperative ileus (28 out of 2769 patients, 1 %) were the most common postoperative complications. Death was reported in three out of 2769 patients (0.1 %). The ICU admitted patients were eight of 2226 patients (0.4 %). CONCLUSION: The robotic technique, especially in obese, can optimize the surgical approach and recovery of such patients with equally if not better outcomes compared to open and/or laparoscopic techniques. PMID- 26861467 TI - Microsatellite analysis of genotype distribution patterns of Candida albicans vulvovaginal candidiasis in Nanjing, China and its association with pregnancy, age and clinical presentation. AB - PURPOSE: To characterize the genotype distribution pattern of Candida albicans associated with vulvovaginal candidiasis (VVC) in Nanjing, China by microsatellite genotyping. METHODS: A questionnaire was completed by each patient diagnosed with VVC. A total of 208 independent C. albicans was isolated from 208 patients. Microsatellite genotyping characterized the genotype distribution by analysis of the CAI locus marker. RESULTS: PCR of CAI fragments showed the three major genotypes contained 30:45, 21:21 and 32:46 alleles among the 51 genotypes detected, accounting for 29.3, 13.0 and 12.0 % of 208 clinical isolates. Genotype distributions had a similar pattern among different clinical presentations (P = 0.219). In both groups of the (21-30) and (31-40) years, 30:45 was the most frequent genotype allele detected. In the (21-30) year females, 16.5 % of the isolated strains had the genotype 21:21, while the same genotype in the group of (31-40) years was 6.9 %. Genotype distributions were significant difference between the pregnant and non-pregnant women (P < 0.001). 30:45 was detected only one in the 23 pregnant women. CONCLUSIONS: The results indicated a unique genotype distribution of C. albicans associated with VVC in Nanjing, eastern China and a different distribution pattern was also detected in pregnant women compared to non-pregnant women. PMID- 26861468 TI - Structured Pharmacist Review of Medication in Older Hospitalised Patients: A Cost Effectiveness Analysis. AB - BACKGROUND: A recent cluster randomised controlled trial (RCT) conducted in an Irish hospital evaluating a structured pharmacist review of medication (SPRM), supported by computerised clinical decision support software (CDSS), demonstrated positive outcomes in terms of reduction of adverse drug reactions (ADR). OBJECTIVE: The aim of this study was to examine the cost effectiveness of pharmacists applying an SPRM in conjunction with CDSS to older hospitalised patients compared with usual pharmaceutical care. METHOD: Cost-effectiveness analysis alongside a cluster RCT. The trial was conducted in a tertiary hospital in the south of Ireland. Patients in the intervention arm (n = 361) received a multifactorial intervention consisting of medicines reconciliation, deployment of CDSS and generation of a pharmaceutical care plan. Patients in the control arm (n = 376) received usual care from the hospital pharmacy team. Incremental cost effectiveness was examined in terms of costs to the healthcare system and an outcome measure of ADRs during an inpatient hospital stay. Uncertainty in the analysis was explored using a cost-effectiveness acceptability curve (CEAC). RESULTS: On average, the intervention arm was the dominant strategy in terms of cost effectiveness. Compared with usual care (control), the intervention was associated with a decrease of ?807 [95% confidence interval (CI) -3443 to 1829; p = 0.548) in mean healthcare cost, and a decrease in the mean number of ADR events per patient of -0.064 (95% CI -0.135 to 0.008; p = 0.081). The probability of the intervention being cost effective at respective threshold values of ?0, ?250, ?500, ?750, ?1000 and ?5000 was 0.707, 0.713, 0.716, 0.718, 0.722 and 0.784, respectively. CONCLUSIONS: Based on the evidence presented, SPRM/CDSS is likely to be determined to be cost effective compared with usual pharmaceutical care. However, neither incremental costs nor effects demonstrated a statistically significant difference, therefore the results of this single-site study should be interpreted with caution. PMID- 26861469 TI - Evaluation of the potential for QTc prolongation in patients with solid tumors receiving nivolumab. AB - PURPOSE: The fully human monoclonal antibody nivolumab binds to the programmed death-1 (PD-1) receptor, blocking interactions between PD-1 and its ligands on tumor cells and preventing T cell exhaustion in patients with cancer. The potential for corrected QT interval (QTc) prolongation was assessed in a subset of patients enrolled in a phase 2 dose-ranging study of nivolumab. METHODS: Triplicate 12-lead electrocardiograms (ECGs) obtained predose and post-dose were assessed by an independent ECG core laboratory. QTc derived from Fridericia's formula (QTcF) was evaluated by central tendency, categorical, and concentration response analyses. RESULTS: No patients had QTcF intervals or changes from baseline in QTcF (DeltaQTcF) exceeding prespecified thresholds indicating borderline or prolonged QTcF (>480 ms) or DeltaQTcF (>60 ms). Among 146 patients randomized to nivolumab 0.3, 2.0, or 10.0 mg/kg every 3 weeks, the maximum increases in mean (+/- SD) ?QTcF at any time point were 4.9 (+/- 13.4), 1.2 (+/- 10.1), and 2.0 (+/- 8.9) ms, respectively. There was no relationship between ?QTcF and nivolumab serum concentration and no association between predicted maximum ?QTcF and mean maximum nivolumab concentration in any dosage group. CONCLUSION: Results of these intensive ECG analyses indicate that nivolumab has no clinically meaningful effect on QTc interval when administered at doses up to 10.0 mg/kg. PMID- 26861472 TI - Ziconotide Monotherapy: A Systematic Review of Randomised Controlled Trials. AB - INTRODUCTION: Chronic neuropathic pain is difficult to treat and is often refractory to most modalities of treatment. Ziconotide is a novel, potent, non opioid, calcium channel blocking agent which has been shown in clinical trials to be effective in treating chronic neuropathic pain. METHODS: EMBASE, MEDLINE, CINAHL Plus and Web of Science electronic databases were searched for English language studies. Reference sections of articles were examined for further papers and the manufacturer of ziconotide was contacted for further unpublished data. Three randomised controlled trials in ziconotide monotherapy were included and subjected to a random effects meta-analysis. RESULTS: All three studies used the similar main outcome measure (visual analogue scale of pain intensity; VASPI) and were therefore comparable. A Jadad score was performed for each paper. Frequent serious adverse events (SAEs) were observed which resulted in two of the studies revising the protocol. The metaanalysis revealed a pooled odds ratio (responders on ziconotide vs. placebo) of 2.77 (95% CI, 1.37 to 5.59). DISCUSSION: The results suggest that ziconotide is beneficial for pain reduction in chronic neuropathic pain. However, there remain some methodological issues that may call into question the validity of the results. It is evident that more work needs to be conducted to further validate the efficacy of ziconotide and to discover new areas of use. PMID- 26861471 TI - The Pharmacology of Spinal Opioids and Ziconotide for the Treatment of Non-Cancer Pain. AB - BACKGROUND: Intrathecal drug delivery has undergone a revitalization following a better understanding of this delivery route and its pharmacokinetics. Driven by patient safety and outcomes, clinicians are motivated to rethink the traditional spinal infusion pump patient selection criteria and indications. We review the current understanding of the pharmacology of commonly employed intrathecal agents and the clinical relevance. METHODS: Search strategies for data acquisition included Medline database, PubMed, Google scholar, along with international and national professional meeting content, with key words including pharmacology of opioids, intrathecal therapy, ziconotide, pharmacokinetics, and intrathecal drug delivery. The search results were limited to the English language. RESULTS: Over 300 papers were identified. The literature was condensed and digested to evaluate the most commonly used medications in practice, sto serve as a foundation for review. We review on-label medications: ziconotide and morphine, and off label medications including fentanyl, sufentail, and hydromorphine. CONCLUSION: Intrathecal therapy has level-one evidence for use for malignant pain and nonmalignant pain, with continued cost savings and improved safety. To most effectively serve our patients, a clear appreciation for the pharmacology of these commonly employed medication is paramount. PMID- 26861473 TI - Plasma adropin level in patients with pseudoexfoliation. AB - The aim of this study was to evaluate plasma adropin levels in patients with pseudoexfoliation (PEX). This retrospective case-control study included 35 patients with PEX and 35 individuals without PEX who served as controls. Plasma adropin levels with triglycerides, total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and haemoglobin A1c (HGBA1C) concentrations were measured in both groups. The mean serum adropin levels were 3.24 +/- 0.95 ng/mL (range, 1.90-7.88 ng/mL) in patients with PEX syndrome and 5.78 +/- 2.85 ng/mL (range, 2.08-5.41 ng/mL) in PEX glaucoma patients. There was no statistically significant difference in mean adropin levels between PEX syndrome and PEX glaucoma patients. However, similar adropin levels were found in the PEX glaucoma patients and the control group (P > 0.05). The mean serum adropin levels were 3.34 +/- 0.89 ng/mL (range, 1.90-5.39 ng/mL) in the PEX group and 5.78 +/- 2.85 ng/mL (range, 3.08-11.06 ng/mL) in the control group. The mean serum adropin level of the PEX group was significantly lower than that of the control group (P < 0.001). There were no significant differences between the two groups in terms of serum glucose, total cholesterol, LDL, HDL, HGBA1C, triglycerides levels, or body mass index (all P > 0.05). Adropin level is lower in patients with PEX. PMID- 26861474 TI - Floral asymmetry and predation risk modify pollinator behavior, but only predation risk decreases plant fitness. AB - Although predators and floral herbivores can potentially decrease plant fitness by changing pollinator behaviors, studies comparing the strength of these factors as well as their additive and interactive effects on pollinator visitation and plant fitness have not been conducted. In this study, we manipulated the floral symmetry and predator presence (artificial crab spiders) on the flowers of the shrub Rubus rosifolius (Rosaceae) in a 2 * 2 factorial randomized block design. We found that asymmetry and predators decreased pollinator visitation (mainly hymenopterans), and overall these factors did not interact (additive effects). The effect of predation risk on pollinator avoidance behavior was 62 % higher than that of floral asymmetry. Furthermore, path analyses revealed that only predation risk cascaded down to plant fitness, and it significantly decreased fruit biomass by 33 % and seed number by 28 %. We also demonstrated that R. rosifolius fitness is indirectly affected by visiting and avoidance behaviors of pollinators. The strong avoidance behavioral response triggered by predation risk may be related to predator pressure upon flowers. Although floral asymmetry caused by herbivory can alter the quality of resources, it should not exert the same evolutionary pressure as that of predator-prey interactions. Our study highlights the importance of considering simultaneous forces, such as predation risk and floral asymmetry, as well as pollinator behavior when evaluating ecological processes involving mutualistic plant-pollinator systems. PMID- 26861475 TI - The Role of Magnetic Resonance Imaging in Prostate Cancer: Focusing on What Really Matters. PMID- 26861476 TI - Systemic inflammatory response syndrome following catheter-directed thrombolysis of acute iliofemoral deep venous thrombosis. AB - Catheter-directed thrombolysis is becoming increasingly considered in the treatment of acute ileofemoral deep vein thrombosis. By targeting occlusive thrombi early, it is possible to mitigate the symptoms of post-thrombotic syndrome, which include oedema, pain, and ulceration. NICE guidelines recommend the use of catheter-directed thrombolysis in those without contraindications to treatment. The main risk of thrombolysis is bleeding; however, other side effects such as allergy have been reported. We present a 50-year-old man who presented with an acute left-sided ileofemoral deep vein thrombosis. He underwent catheter directed thrombolysis in our centre to good effect, and ultimately he required stenting due to the presence of a May-Thurner lesion. His first day of thrombolysis, however, was complicated by a massive systemic inflammatory response syndrome response resulting in pyrexia and tachycardia, rigors, and myalgia. His deterioration in observations corresponded with a huge rise in D dimer levels from an admission baseline of 1465 ng/ml to 182,835 ng/ml. We hypothesize that rapid breakdown of thrombus in this patient resulted in a lysis type syndrome, presenting with a systemic inflammatory response syndrome response. Several questions are raised here including why the patient responded in this way, and whether there could be a way to predict response ahead of time? Fortunately, our patient came to no harm and continues to do well, with no evidence of further thrombosis on surveillance ultrasound. This case highlights an important complication of thrombolysis and reminds us that complications are not just limited to bleeding. Despite the short-term effects in this young fit patient, concerns must be raised about potential safety in the frailer and more elderly patient demographic in which such a large inflammatory response could be more detrimental. PMID- 26861477 TI - TGF-beta1 inhibits the apoptosis of pulmonary arterial smooth muscle cells and contributes to pulmonary vascular medial thickening via the PI3K/Akt pathway. AB - Previous studies have highlighted that the transforming growth factor-beta1 (TGF beta1) pathway may be activated by hypoxic conditions. TGF-beta1 also participates in the regulation of proliferation, differentiation, migration and apoptosis of various cell types. Furthermore, TGF-beta1 has been reported to participate in the regulation of the progression of pulmonary arterial hypertension (PAH). However, the effect of TGF-beta1 on pulmonary arterial smooth muscle cells (PASMCs) and the corresponding molecular mechanisms remain unclear. The present study aimed to determine whether TGF-beta1 protects against cell apoptosis in PASMCs, and identify the underlying molecular mechanisms. Western blotting, MTT and lactate dehydrogenase activity assays were performed, and the activity of caspase-3 and caspase-9 was detected in order to investigate the hypothesis. It was determined that TGF-beta1 may facilitate cell growth in a dose dependent manner in serum-starved PASMCs. Furthermore, it was observed that apoptosis in serum-starved PASMCs was inhibited by TGF-beta1 via regulation of the expression levels of mitochondrial membrane proteins. Additionally, the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway was found to be activated by TGF-beta1 in PASMCs, while the inhibition of PI3K/Akt signaling also prevented the apoptosis-limiting effects of TGF-beta1. These observations suggest that TGF-beta1 protects PASMCs from apoptosis and contributes to pulmonary vascular medial thickening via the PI3K/Akt pathway. PMID- 26861479 TI - Pathway and sink activity for photosynthate translocation in Pisolithus extraradical mycelium of ectomycorrhizal Pinus thunbergii seedlings. AB - The purpose of this study was to identify the pathway and sink activity of photosynthate translocation in the extraradical mycelium (ERM) of a Pisolithus isolate. We labelled ectomycorrhizal (ECM) Pinus thunbergii seedlings with (14)CO2 and followed (14)C distribution within the ERM by autoradiography. (14)C photosynthate translocation in the ERM resulted in (14)C distribution in rhizomorphs throughout the ERM, with (14)C accumulation at the front. When most radial mycelial connections between ECM root tips and the ERM front were cut, the whole allocation of (14)C photosynthates to the ERM was reduced. However, the overall pattern of (14)C distribution in the ERM was maintained even in regions immediately above and below the cut, with no local (14)C depletion or accumulation. We inferred from this result that every portion in the ERM has a significant sink activity and a definite sink capacity for photosynthates and that photosynthates detour the cut and reach throughout the ERM by translocation in every direction. Next, we prepared paired ECM seedlings, ERMs of which had been connected with each other by hyphal fusion, alongside, labelled the left seedling with (14)CO2, and shaded none, one or both of them. (14)C photosynthates were acropetally and basipetally translocated from the left ERM to ECM root tips of the right seedling through rhizomorphs in the left and right ERMs, respectively. With the left seedling illuminated, (14)C translocation from the left to the right ERM increased by shading the right seedling. This result suggests that reduced photosynthate transfer from the host to its ERM increased sink activity of the ERM. PMID- 26861478 TI - Prenatal and infant paracetamol exposure and development of asthma: the Norwegian Mother and Child Cohort Study. AB - BACKGROUND: Paracetamol exposure has been positively associated with asthma development. The relative importance of prenatal vs infant exposure and confounding by indication remains elusive. We examined the association of prenatal and infant (first 6 months) paracetamol exposure with asthma development while addressing confounding by indication. METHODS: We used information from the Norwegian Mother and Child Cohort Study, including 53169 children for evaluation of current asthma at 3 years, 25394 for current asthma at 7 years and 45607 for dispensed asthma medications at 7 years in the Norwegian Prescription Database. We calculated adjusted relative risks (adj. RR) and 95% confidence intervals (CI) using log-binomial regression. RESULTS: There were independent modest associations between asthma at 3 years with prenatal paracetamol exposure (adj. RR 1.13; 95% CI: 1.02-1.25) and use of paracetamol during infancy (adj. RR 1.29; 95% CI: 1.16-1.45). The results were consistent for asthma at 7 years. The associations with prenatal paracetamol exposure were seen for different indications (pain, respiratory tract infections/influenza and fever). Maternal pain during pregnancy was the only indication that showed an association both with and without paracetamol use. Maternal paracetamol use outside pregnancy and paternal paracetamol use were not associated with asthma development. In a secondary analysis, prenatal ibuprofen exposure was positively associated with asthma at 3 years but not asthma at 7 years. CONCLUSIONS: This study provides evidence that prenatal and infant paracetamol exposure have independent associations with asthma development. Our findings suggest that the associations could not be fully explained by confounding by indication. PMID- 26861480 TI - Hydraulic conductivity and aquaporin transcription in roots of trembling aspen (Populus tremuloides) seedlings colonized by Laccaria bicolor. AB - Ectomycorrhizal fungi have been reported to increase root hydraulic conductivity (L pr) by altering apoplastic and plasma membrane intrinsic protein (PIP) mediated cell-to-cell water transport pathways in associated roots, or to have little effect on root water transport, depending on the interacting species and imposed stresses. In this study, we investigated the water transport properties and PIP transcription in roots of aspen (Populus tremuloides) seedlings colonized by the wild-type strain of Laccaria bicolor and by strains overexpressing a major fungal water-transporting aquaporin JQ585595. Inoculation of aspen seedlings with L. bicolor resulted in about 30 % colonization rate of root tips, which developed dense mantle and the Hartig net that was restricted in the modified root epidermis. Transcript abundance of the aspen aquaporins PIP1;2, PIP2;1, and PIP2;2 decreased in colonized root tips. Root colonization by JQ585595 overexpressing strains had no significant impact on seedling shoot water potentials, gas exchange, or dry mass; however, it led to further decrease in transcript abundance of PIP1;2 and PIP2;3 and the significantly lower L pr than in non-inoculated roots. These results, taken together with our previous study that showed enhanced root water hydraulics of L. bicolor-colonized white spruce (Picea glauca), suggest that the impact of L. bicolor on root hydraulics varies by the ectomycorrhiza-associated tree species. PMID- 26861481 TI - Genomic insights into the carbohydrate catabolism of Cairneyella variabilis gen. nov. sp. nov., the first reports from a genome of an ericoid mycorrhizal fungus from the southern hemisphere. AB - This paper describes a novel species of ericoid mycorrhizal fungus from Australia, Cairneyella variabilis, Midgley and Tran-Dinh, gen. nov. sp. nov. The genome of C. variabilis was sequenced and a draft genome assembled. The draft genome of C. variabilis is 52.4 Mbp in length, and to our knowledge, this is the first study to present a genome of an ericoid mycorrhizal fungus from the southern hemisphere. Using the SignalP and dbCAN bioinformatic pipelines, a study of the catabolic potential of C. variabilis was undertaken and showed genes for an array of degradative enzymes, most of which appear to be secreted from the hyphae, to access a suite of different carbon sources. Isolates of C. variabilis have been previously shown to utilise cellulose, carboxymethyl cellulose (CMC), cellobiose, xylan, pectin, starch and tannic acid for growth, and in the current study, putative enzymes for these processes were revealed. These enzymes likely play key roles in nutrient cycling and other edaphic processes in heathland environments. ITS phylogenetic analyses showed C. variabilis to be distinct from the fungi of the "Hymenoscyphus ericae aggregate". PMID- 26861482 TI - Impact of Heterobasidion root-rot on fine root morphology and associated fungi in Picea abies stands on peat soils. AB - We examined differences in fine root morphology, mycorrhizal colonisation and root-inhabiting fungal communities between Picea abies individuals infected by Heterobasidion root-rot compared with healthy individuals in four stands on peat soils in Latvia. We hypothesised that decreased tree vitality and alteration in supply of photosynthates belowground due to root-rot infection might lead to changes in fungal communities of tree roots. Plots were established in places where trees were infected and in places where they were healthy. Within each stand, five replicate soil cores with roots were taken to 20 cm depth in each root-rot infected and uninfected plot. Root morphological parameters, mycorrhizal colonisation and associated fungal communities, and soil chemical properties were analysed. In three stands root morphological parameters and in all stands root mycorrhizal colonisation were similar between root-rot infected and uninfected plots. In one stand, there were significant differences in root morphological parameters between root-rot infected versus uninfected plots, but these were likely due to significant differences in soil chemical properties between the plots. Sequencing of the internal transcribed spacer of fungal nuclear rDNA from ectomycorrhizal (ECM) root morphotypes of P. abies revealed the presence of 42 fungal species, among which ECM basidiomycetes Tylospora asterophora (24.6 % of fine roots examined), Amphinema byssoides (14.5 %) and Russula sapinea (9.7 %) were most common. Within each stand, the richness of fungal species and the composition of fungal communities in root-rot infected versus uninfected plots were similar. In conclusion, Heterobasidion root-rot had little or no effect on fine root morphology, mycorrhizal colonisation and composition of fungal communities in fine roots of P. abies growing on peat soils. PMID- 26861470 TI - Current and Future Issues in the Development of Spinal Agents for the Management of Pain. AB - Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety. PMID- 26861484 TI - The effect of training and breed group on problem-solving behaviours in dogs. AB - Dogs have become the focus of cognitive studies looking at both their physical and social problem-solving abilities (Bensky et al. in Adv Stud Behav, 45:209 387, 2013), but very little is known about the environmental and inherited factors that may affect these abilities. In the current study, we presented a manipulation task (a puzzle box) and a spatial task (the detour) to 128 dogs belonging to four different breed groups: Herding, Mastiff-like, Working and Retrievers (von Holdt et al. in Nature 464:898-902, 2010). Within each group, we tested highly trained and non-trained dogs. Results showed that trained dogs were faster at obtaining the reward in the detour task. In the manipulation task, trained dogs approached the apparatus sooner in the first familiarization trial, but no effect of breed emerged on this variable. Furthermore, regardless of breed, dogs in the trained group spent proportionally more time interacting with the apparatus and were more likely to succeed in the test trial than dogs in the non-trained group, whereas regardless of training, dogs in the working breed group were more likely to succeed than dogs in the retriever and herding breed groups (but not the mastiff-like group). Finally, trained dogs were less likely to look at a person than non-trained dogs during testing, but dogs in the herding group more likely to do so than dogs in the retriever and working but not the mastiff-like breed groups. Overall, results reveal a strong influence of training experience but less consistent differences between breed groups on different components thought to affect problem solving. PMID- 26861483 TI - Biochemical and ecophysiological responses to manganese stress by ectomycorrhizal fungus Pisolithus tinctorius and in association with Eucalyptus grandis. AB - At relatively low concentrations, the element manganese (Mn) is essential for plant metabolism, especially for photosynthesis and as an enzyme antioxidant cofactor. However, industrial and agricultural activities have greatly increased Mn concentrations, and thereby contamination, in soils. We tested whether and how growth of Pisolithus tinctorius is influenced by Mn and glucose and compare the activities of oxidative stress enzymes as biochemical markers of Mn stress. We also compared nutrient accumulation, ecophysiology, and biochemical responses in Eucalyptus grandis which had been colonized by the ectomycorrhizal Pisolithus tinctorius with those which had not, when both were exposed to increasing Mn concentrations. In vitro experiments comprised six concentrations of Mn in three concentrations of glucose. In vivo experiments used plants colonized by Pisolithus tinctorius, or not colonized, grown with three concentrations of Mn (0, 200, and 1000 MUM). We found that fungal growth and glucose concentration were correlated, but these were not influenced by Mn levels in the medium. The anti-oxidative enzymes catalase and glutathione S-transferase were both activated when the fungus was exposed to Mn. Also, mycorrhizal plants grew more and faster than non-mycorrhizal plants, whatever Mn exposure. Photosynthesis rate, intrinsic water use efficiency, and carboxylation efficiency were all inversely correlated with Mn concentration. Thus, we originally show that the ectomycorrhizal fungus provides protection for its host plants against varying and potentially toxic concentrations of Mn. PMID- 26861486 TI - Can the Dying Phase Be Masked by the Use of Dexamethasone? A Case Report. AB - Recognition of the dying phase, i.e., the period during which death is expected to occur within hours or days, is important because it enables marking the imminence of death, informing the patient and his relatives, and adjusting care where needed. Careful communication about a patient's limited prognosis prepares patients and their family for impending death and saying goodbye. The authors describe two cases of patients dying a relatively unexpected death in a hospice, which is uncommon in this setting. These unexpected deaths had a severe impact on the relatives and on the professional care team. Both patients used dexamethasone. The authors postulate that there is a relationship between the use of dexamethasone and difficulty in recognizing the dying phase. Dexamethasone can make patients feel better, increase their appetite, and influence the stress response. These effects could mask the signs of impending death, such as "being bedbound," "only drinking sips," and "being subcomatose." Review of the literature yielded no articles that support or reject this hypothesis. Because dexamethasone is used regularly in the palliative phase of a chronic disease, there is a need for further exploration of its effects in the dying phase. PMID- 26861487 TI - Surveillance colonoscopy after endoscopic treatment for colorectal neoplasia: From the standpoint of the Asia-Pacific region. AB - Colonoscopy is considered the gold standard to detect and remove colorectal neoplasia. The efficacy of colonoscopy with polypectomy to reduce colorectal cancer incidence and mortality has been demonstrated. Recently, post-polypectomy surveillance colonoscopy has become a necessary intervention in daily practice not only in Western countries but also in the Asia-Pacific region. Therefore, it is crucial to establish new clinical practice guidelines to reduce the number of unnecessary surveillance colonoscopies in order to create space for screening colonoscopy. The Asia-Pacific Consensus group recommended that surveillance colonoscopy interval should be tailored according to risk level of index colonoscopy. However, precise guidelines on interval of surveillance cannot be given because of a lack of prospective data. According to Korean and Australian guidelines, surveillance intervals after index colonoscopy of 5 years for low risk subjects and 3 years for high-risk subjects are recommended in Asia-Pacific regions at present. Prospective data including long-term outcomes from the Japan Polyp Study, which is a multicenter randomized control trial, would be useful to establish the Asia-Pacific consensus in the near future. PMID- 26861485 TI - Increased Paracrine Immunomodulatory Potential of Mesenchymal Stromal Cells in Three-Dimensional Culture. AB - Mesenchymal stromal/stem cells (MSCs) have been investigated extensively through the past years, proving to have great clinical therapeutic potential. In vitro cultivation of MSCs in three-dimensional (3D) culture systems, such as scaffolds, hydrogels, or spheroids, have recently gained attention for tissue engineering applications. Studies on MSC spheroids demonstrated that such cultivation increased the paracrine immunomodulatory potential of the MSCs, accompanied by phenotypic alterations. In this review, we gather results from recent experimental studies on the immunomodulatory abilities of MSCs when cultured as spheroids or in biomaterials like scaffolds or hydrogels compared to regular two dimensional (2D) culture and show that alterations occurring to MSCs in spheroids also occur in MSCs in biomaterials. We provide a brief description of known mechanisms of MSC immunomodulatory capacity and how they are altered in the two 3D culture systems, together with phenotypic cellular changes. Based on the present knowledge, we highlight vital areas in need of further investigation. The impact of 3D environments on immunomodulation has great potential for tissue engineering and cellular therapy, and this is the first review to gather this knowledge with a comparison across different 3D environments. PMID- 26861488 TI - Simultaneous and sequential hemorrhage of multiple cerebral cavernous malformations: a case report. AB - BACKGROUND: The etiology of cerebral cavernous malformation hemorrhage is not well understood. Causative physiologic parameters preceding hemorrhagic cavernous malformation events are often not reported. We present a case of an individual with sequential simultaneous hemorrhages in multiple cerebral cavernous malformations with a new onset diagnosis of hypertension. CASE PRESENTATION: A 42 year-old white man was admitted to our facility with worsening headache, left facial and tongue numbness, dizziness, diplopia, and elevated blood pressure. His past medical history was significant for new onset diagnosis of hypertension and chronic seasonal allergies. Serial imaging over the ensuing 8 days revealed sequential hemorrhagic lesions. He underwent suboccipital craniotomy for resection of the lesions located in the fourth ventricle and right cerebellum. One month after surgery, he had near complete resolution of his symptoms with mild residual vertigo but symptomatic chronic hypertension. CONCLUSIONS: Many studies have focused on genetic and inflammatory mechanisms contributing to cerebral cavernous malformation rupture, but few have reported on the potential of hemodynamic changes contributing to cerebral cavernous malformation rupture. Systemic blood pressure changes clearly have an effect on angioma pressures. When considering the histopathological features of cerebral cavernous malformation architecture, changes in arterial pressure could cause meaningful alterations in hemorrhage propensity and patterns. PMID- 26861489 TI - Matrix metalloproteinase-11 as a marker of metastasis and predictor of poor survival in urothelial carcinomas. AB - BACKGROUND AND OBJECTIVES: Urothelial carcinomas (UC) of urinary bladder (UB) and upper urinary tract (UT) are heterogeneous diseases with high morbidity and mortality. We looked for genes with metalloendopeptidase activity in a published UBUC transcriptomic database (GSE31684):MMP-11 was the most significant, showing stepwise up-regulation. We analyzed MMP-11 expression and association with clinicopathologic factors and survival in our well-characterized cohort of UCs. METHODS: We determined MMP-11 expression in 295 UBUCs and 340 UTUCs with immunohistochemistry, evaluated by H-score. In a retrospective study, MMP-11 expression was correlated with clinicopathologic features and with disease specific survival (DSS) and metastasis-free survival (MeFS). The statistical significance was evaluated with univariate and multivariate analyses. RESULTS: High MMP-11 expression was significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular and perineural invasion, and frequent mitoses. In multivariate Cox regression analyses, which adjusted for standard clinicopathologic characteristics, MMP-11 expression was independently associated with cancer-specific mortality (hazard ratio [HR] in UTUC:3.027, P = 0.005; in UBUC: 2.631, P = 0.010) and with metastasis development (HR in UTUC:2.261, P = 0.018; in UBUC:1.801, P = 0.026). CONCLUSIONS: MMP-11 overexpression is associated with aggressive tumor phenotype and unfavorable clinical outcome in UTUC and UBUC, suggesting it may serve as a novel prognostic and therapeutic target. J. Surg. Oncol. 2016;113:700-707. (c) 2016 Wiley Periodicals, Inc. PMID- 26861491 TI - Meningoencephalitis with microinfarcts in early neuroborreliosis. PMID- 26861490 TI - Aleglitazar, a Balanced Dual PPARalpha and -gamma Agonist, Protects the Heart Against Ischemia-Reperfusion Injury. AB - PURPOSE: To evaluate whether aleglitazar (Ale), a dual PPARalpha/gamma agonist, has additive effects on myocardial protection against ischemia-reperfusion injury. METHODS: Human cardiomyocytes (HCMs), cardiomyocytes from cardiac specific PPARgamma knockout (MCM-PPARgamma (CKO) ) or wild type (MCM-WT) mice were incubated with different concentrations of Ale, and subjected to simulated ischemia-reperfusion (SIR) or normoxic conditions (NSIR). Cell viability, apoptosis and caspase-3 activity were determined. HCMs were transfected with siRNA against PPARalpha (siPPARalpha) or PPARgamma (siPPARgamma) followed by incubation with Ale. PPARalpha/gamma DNA binding capacity was measured. Cell viability, apoptosis and levels of P-AKT and P-eNOS were assessed. Infarct size following 30 min coronary artery occlusion and 24 h reperfusion were assessed in WT and db/db diabetic mice following 3-day pretreatment with vehicle, Ale or glimeperide. RESULTS: Ale (at concentrations of 150-600 nM) increased cell viability and reduced apoptosis in HCMs, MCM-WT and MCM-PPAR (CKO) exposed to SIR. In HCM, the protective effect was partially blocked by siPPARalpha alone or siPPARgamma alone, and completely blocked by siPPARalpha+siPPARgamma. Ale increased P-Akt/P-eNOS in HCMs. P-Akt or P-eNOS levels were decreased when PPARalpha alone, PPARgamma alone and especially when both were knocked down. Peritoneal GTTs revealed that db/db mice had developed impaired glucose tolerance and insulin sensitivity, which were normalized by Ale or glimepiride treatment. Ale, but not glimepiride, limited infarct size in both WT and diabetic mice after ischemia-reperfusion. CONCLUSIONS: Ale protects against myocardial apoptosis caused by hypoxia-reoxygenation in vitro and reduces infarct size in vivo. PMID- 26861492 TI - A Novel Universal Cementation Technique for Implant-Supported Crowns with Subgingival Margins. AB - Restoration of implant crowns with subgingival margins has always been a challenge. If done precisely it leads to better treatment outcomes and prognosis. An incorrect technique and improper execution of the luting procedure are known to cause a high incidence of peri-implant disease due to incomplete elimination of the luting agent. Deep subgingival abutment margins are difficult to recognize, and cement removal in these cases becomes complicated if the sulcus depth is greater than 3 mm. Irrespective of the type of instrument used to remove the excess cement, scratches on the abutment and some cement remnants are consistently noticed. Therefore elimination of excess luting agent before the prosthesis is inserted intraorally is considered an effective technique to prevent complications due to excess luting agent. This article presents a chairside universal technique for cementation of implant crowns on abutments with deep subgingival margins. This technique attempts to minimize the amount of excess cement in peri-implant tissue. PMID- 26861493 TI - No genotoxicity in rat blood cells upon 3- or 6-month inhalation exposure to CeO2 or BaSO4 nanomaterials. AB - In the course of a 2-year combined chronic toxicity-carcinogenicity study performed according to Organisation for Economic Co-operation and Development (OECD) Test Guideline 453, systemic (blood cell) genotoxicity of two OECD representative nanomaterials, CeO2 NM-212 and BaSO4 upon 3- or 6-month inhalation exposure to rats was assessed. DNA effects were analysed in leukocytes using the alkaline Comet assay, gene mutations and chromosome aberrations were measured in erythrocytes using the flow cytometric Pig-a gene mutation assay and the micronucleus test (applying both microscopic and flow cytometric evaluation), respectively. Since nano-sized CeO2 elicited lung effects at concentrations of 5mg/m3 (burdens of 0.5mg/lung) in the preceding range-finding study, whereas nano sized BaSO4 did not induce any effect, female rats were exposed to aerosol concentrations of 0.1 up to 3mg/m3 CeO2 or 50mg/m3 BaSO4 nanomaterials (6h/day; 5 days/week; whole-body exposure). The blood of animals treated with clean air served as negative control, whereas blood samples from rats treated orally with three doses of 20mg/kg body weight ethylnitrosourea at 24h intervals were used as positive controls. As expected, ethylnitrosourea elicited significant genotoxicity in the alkaline Comet and Pig-a gene mutation assays and in the micronucleus test. By contrast, 3- and 6-month CeO2 or BaSO4 nanomaterial inhalation exposure did not elicit significant findings in any of the genotoxicity tests. The results demonstrate that subchronic inhalation exposure to different low doses of CeO2 or to a high dose of BaSO4 nanomaterials does not induce genotoxicity on the rat hematopoietic system at the DNA, gene or chromosome levels. PMID- 26861495 TI - Corrigendum. PMID- 26861496 TI - Corrigendum. PMID- 26861494 TI - Translating evidence-based guidelines to improve feedback practices: the interACT case study. AB - BACKGROUND: There has been a substantial body of research examining feedback practices, yet the assessment and feedback landscape in higher education is described as 'stubbornly resistant to change'. The aim of this paper is to present a case study demonstrating how an entire programme's assessment and feedback practices were re-engineered and evaluated in line with evidence from the literature in the interACT (Interaction and Collaboration via Technology) project. METHODS: Informed by action research the project conducted two cycles of planning, action, evaluation and reflection. Four key pedagogical principles informed the re-design of the assessment and feedback practices. Evaluation activities included document analysis, interviews with staff (n = 10) and students (n = 7), and student questionnaires (n = 54). Descriptive statistics were used to analyse the questionnaire data. Framework thematic analysis was used to develop themes across the interview data. RESULTS: InterACT was reported by students and staff to promote self-evaluation, engagement with feedback and feedback dialogue. Streamlining the process after the first cycle of action research was crucial for improving engagement of students and staff. The interACT process of promoting self-evaluation, reflection on feedback, feedback dialogue and longitudinal perspectives of feedback has clear benefits and should be transferable to other contexts. CONCLUSIONS: InterACT has involved comprehensive re-engineering of the assessment and feedback processes using educational principles to guide the design taking into account stakeholder perspectives. These principles and the strategies to enact them should be transferable to other contexts. PMID- 26861497 TI - Improved mass resolution and mass accuracy in TOF-SIMS spectra and images using argon gas cluster ion beams. AB - The popularity of argon gas cluster ion beams (Ar-GCIB) as primary ion beams in time-of-flight secondary ion mass spectrometry (TOF-SIMS) has increased because the molecular ions of large organic- and biomolecules can be detected with less damage to the sample surfaces. However, Ar-GCIB is limited by poor mass resolution as well as poor mass accuracy. The inferior quality of the mass resolution in a TOF-SIMS spectrum obtained by using Ar-GCIB compared to the one obtained by a bismuth liquid metal cluster ion beam and others makes it difficult to identify unknown peaks because of the mass interference from the neighboring peaks. However, in this study, the authors demonstrate improved mass resolution in TOF-SIMS using Ar-GCIB through the delayed extraction of secondary ions, a method typically used in TOF mass spectrometry to increase mass resolution. As for poor mass accuracy, although mass calibration using internal peaks with low mass such as hydrogen and carbon is a common approach in TOF-SIMS, it is unsuited to the present study because of the disappearance of the low-mass peaks in the delayed extraction mode. To resolve this issue, external mass calibration, another regularly used method in TOF-MS, was adapted to enhance mass accuracy in the spectrum and image generated by TOF-SIMS using Ar-GCIB in the delayed extraction mode. By producing spectra analyses of a peptide mixture and bovine serum albumin protein digested with trypsin, along with image analyses of rat brain samples, the authors demonstrate for the first time the enhancement of mass resolution and mass accuracy for the purpose of analyzing large biomolecules in TOF-SIMS using Ar-GCIB through the use of delayed extraction and external mass calibration. PMID- 26861498 TI - Random sample consensus combined with partial least squares regression (RANSAC PLS) for microbial metabolomics data mining and phenotype improvement. AB - In recent years, the advent of high-throughput omics technology has made possible a new class of strain engineering approaches, based on identification of possible gene targets for phenotype improvement from omic-level comparison of different strains or growth conditions. Metabolomics, with its focus on the omic level closest to the phenotype, lends itself naturally to this semi-rational methodology. When a quantitative phenotype such as growth rate under stress is considered, regression modeling using multivariate techniques such as partial least squares (PLS) is often used to identify metabolites correlated with the target phenotype. However, linear modeling techniques such as PLS require a consistent metabolite-phenotype trend across the samples, which may not be the case when outliers or multiple conflicting trends are present in the data. To address this, we proposed a data-mining strategy that utilizes random sample consensus (RANSAC) to select subsets of samples with consistent trends for construction of better regression models. By applying a combination of RANSAC and PLS (RANSAC-PLS) to a dataset from a previous study (gas chromatography/mass spectrometry metabolomics data and 1-butanol tolerance of 19 yeast mutant strains), new metabolites were indicated to be correlated with tolerance within certain subsets of the samples. The relevance of these metabolites to 1-butanol tolerance were then validated from single-deletion strains of corresponding metabolic genes. The results showed that RANSAC-PLS is a promising strategy to identify unique metabolites that provide additional hints for phenotype improvement, which could not be detected by traditional PLS modeling using the entire dataset. PMID- 26861499 TI - Carbon-Based Solid-State Calcium Ion-Selective Microelectrode and Scanning Electrochemical Microscopy: A Quantitative Study of pH-Dependent Release of Calcium Ions from Bioactive Glass. AB - Solid-state ion-selective electrodes are used as scanning electrochemical microscope (SECM) probes because of their inherent fast response time and ease of miniaturization. In this study, we report the development of a solid-state, low poly(vinyl chloride), carbon-based calcium ion-selective microelectrode (Ca(2+) ISME), 25 MUm in diameter, capable of performing an amperometric approach curve and serving as a potentiometric sensor. The Ca(2+)-ISME has a broad linear response range of 5 MUM to 200 mM with a near Nernstian slope of 28 mV/log[a(Ca(2+))]. The calculated detection limit for Ca(2+)-ISME is 1 MUM. The selectivity coefficients of this Ca(2+)-ISME are log K(Ca(2+),A) = -5.88, -5.54, and -6.31 for Mg(2+), Na(+), and K(+), respectively. We used this new type of Ca(2+)-ISME as an SECM probe to quantitatively map the chemical microenvironment produced by a model substrate, bioactive glass (BAG). In acidic conditions (pH 4.5), BAG was found to increase the calcium ion concentration from 0.7 mM ([Ca(2+)] in artificial saliva) to 1.4 mM at 20 MUm above the surface. In addition, a solid-state dual SECM pH probe was used to correlate the release of calcium ions with the change in local pH. Three-dimensional pH and calcium ion distribution mapping were also obtained by using these solid-state probes. The quantitative mapping of pH and Ca(2+) above the BAG elucidates the effectiveness of BAG in neutralizing and releasing calcium ions in acidic conditions. PMID- 26861500 TI - Age-associated changes in DNA methylation across multiple tissues in an inbred mouse model. AB - Epigenetic disruption has been implicated in many diseases of aging, and age associated DNA methylation changes at specific genomic loci in humans are strongly correlated with chronological age. The aim of this study was to explore the specificity of selected age-associated differentially methylated positions (aDMPs) identified in human epidemiological studies by quantifying DNA methylation across multiple tissues in homologous regions of the murine genome. We selected four high-confidence aDMPs (located in the vicinity of the ELOVL2, GLRA1, MYOD1 and PDE4C genes) and quantified DNA methylation across these regions in four tissues (blood, lung, cerebellum and hippocampus) from male and female C57BL/6J mice, ranging in age from fetal (embryonic day 17) to 630 days. We observed tissue-specific age-associated changes in DNA methylation that was directionally consistent with those observed in humans. These findings lend further support to the notion that changes in DNA methylation are associated with chronological age and suggest that these processes are often conserved across tissues and between mammalian species. Our data highlight the relevance of utilizing model systems, in which environmental and genetic influences can be carefully controlled, for the further study of these phenomena. PMID- 26861501 TI - Absence of N-terminal acetyltransferase diversification during evolution of eukaryotic organisms. AB - Protein N-terminal acetylation is an ancient and ubiquitous co-translational modification catalyzed by a highly conserved family of N-terminal acetyltransferases (NATs). Prokaryotes have at least 3 NATs, whereas humans have six distinct but highly conserved NATs, suggesting an increase in regulatory complexity of this modification during eukaryotic evolution. Despite this, and against our initial expectations, we determined that NAT diversification did not occur in the eukaryotes, as all six major human NATs were most likely present in the Last Eukaryotic Common Ancestor (LECA). Furthermore, we also observed that some NATs were actually secondarily lost during evolution of major eukaryotic lineages; therefore, the increased complexity of the higher eukaryotic proteome occurred without a concomitant diversification of NAT complexes. PMID- 26861503 TI - Highly selective polymer electrolyte membranes consisting of poly(2-ethyl-2 oxazoline) and Cu(NO3)2 for SF6 separation. AB - Polymer electrolyte membranes consisting of Cu(NO3)2 and poly(2-ethyl-2 oxazoline) (POZ) were prepared for SF6/N2 separation. It was anticipated that repulsive forces would be operative between the negative charge of water and the F atoms of SF6 when Cu(NO3)2 in the composite was solvated by water, and that the barrier effect of Cu(2+) ions would be activated. In fact, Cu(NO3)2 solvated by water in the POZ membrane was observed to have more higher-order ionic aggregates than free ions or ion pairs, as confirmed by FT-Raman spectroscopy. Thus, when Cu(NO3)2 solvated by water was incorporated into the POZ matrix, the N2/SF6 selectivity increased to 28.0 with a N2 permeance of 11.2 GPU at a POZ/Cu(NO3)2 mole ratio of 1:0.7. The coordinative interaction of Cu(NO3)2 with the carbonyl group in POZ was confirmed by FT-IR spectroscopy and TGA, and the film thickness of the membrane was determined from SEM analysis. PMID- 26861502 TI - The effector candidate repertoire of the arbuscular mycorrhizal fungus Rhizophagus clarus. AB - BACKGROUND: Arbuscular mycorrhizal fungi (AMF) form an ecologically important symbiosis with more than two thirds of studied land plants. Recent studies of plant-pathogen interactions showed that effector proteins play a key role in host colonization by controlling the plant immune system. We hypothesise that also for symbiotic-plant interactions the secreted effectome of the fungus is a major component of communication and the conservation level of effector proteins between AMF species may be indicative whether they play a fundamental role. RESULTS: In this study, we used a bioinformatics pipeline to predict and compare the effector candidate repertoire of the two AMF species, Rhizophagus irregularis and Rhizophagus clarus. Our in silico pipeline revealed a list of 220 R. irregularis candidate effector genes that create a valuable information source to elucidate the mechanism of plant infection and colonization by fungi during AMF symbiotic interaction. While most of the candidate effectors show no homologies to known domains or proteins, the candidates with homologies point to potential roles in signal transduction, cell wall modification or transcription regulation. A remarkable aspect of our work is presence of a large portion of the effector proteins involved in symbiosis, which are not unique to each fungi or plant species, but shared along the Glomeromycota phylum. For 95% of R. irregularis candidates we found homologs in a R. clarus genome draft generated by Illumina high-throughput sequencing. Interestingly, 9% of the predicted effectors are at least as conserved between the two Rhizophagus species as proteins with housekeeping functions (similarity > 90%). Therefore, we state that this group of highly conserved effector proteins between AMF species may play a fundamental role during fungus-plant interaction. CONCLUSIONS: We hypothesise that in symbiotic interactions the secreted effectome of the fungus might be an important component of communication. Identification and functional characterization of the primary AMF effectors that regulate symbiotic development will help in understanding the mechanisms of fungus-plant interaction. PMID- 26861504 TI - Veno-veno-arterial extracorporeal membrane oxygenation treatment in patients with severe acute respiratory distress syndrome and septic shock. PMID- 26861506 TI - Pulmonary Nocardiosis in a Multiple Myeloma Patient Treated with Proteasome Inhibitors. AB - BACKGROUND: The use of proteasome inhibitors like Bortezomib to treat multiple myeloma has been associated with increased rates of opportunistic infections, including Nocardia, especially when lymphopenia is present. The prevalence or association of such infections with newer agents like Carfilzomib is not known. CASE REPORT: A 71-year-old man with multiple myeloma presented with a 6-week history of respiratory symptoms and cyclic fevers. He was undergoing chemotherapy with Carfilzomib. Work-up revealed severe lymphopenia and a CT chest showed multiple lung nodules and a mass-like consolidation. He underwent a bronchoscopy, and respiratory cultures grew Nocardia species. He responded well to intravenous antibiotics with resolution of symptoms and CT findings. CONCLUSIONS: With the introduction of newer agents like Carfilzomib for the treatment of multiple myeloma, clinicians must maintain a high degree of suspicion for opportunistic infections to achieve early diagnosis and treatment. PMID- 26861505 TI - Measurement of health-related quality of life in adult patients with birch pollen associated food allergy. AB - BACKGROUND: The "Food Allergy Quality of Life Questionnaire - Adult Form" (FAQLQ AF) is the first freely available questionnaire for the assessment of health related quality of life (HRQL) in adults with food allergy (FA). We present validation data for the German version as well as data on HRQL in patients with birch pollen-associated FA. PATIENTS AND METHODS: The Dutch FAQLQ-AF (scale from 1-7, no impairment - maximum impairment) was translated into German. Subsequently, 73 consecutive patients with a history of birch pollen-associated FA (52 women, median age 43 years) were surveyed using questions regarding triggers and symptoms of their FA as well as questions contained in the FAQLQ-AF. Construct validity, internal consistency, and discriminative ability were analyzed. RESULTS: The foods most frequently reported to elicit allergic reactions included apple (78%), hazelnut (75%), soy drinks (55%), and carrot (52%). Thirty percent of patients exclusively reported symptoms consistent with oral allergy syndrome (OAS). Sixty-four percent reported OAS combined with systemic symptoms, and only 6% were exclusively affected by non-OAS symptoms. The German FAQLQ-AF showed good construct validity (correlation with the food allergy independent measure: r = 0.81; p < 0.001) and excellent internal consistency (Cronbachs alpha = 0.98). The mean overall FAQLQ-AF score was 3.7. Women, elderly individuals, and those with multiple relevant food allergies showed a greater impairment of HRQL. CONCLUSIONS: The German FAQLQ-AF questionnaire is a reliable and valid tool for measuring HRQL in patients with birch pollen-associated food allergy. PMID- 26861507 TI - Doped and undoped graphene platforms: the influence of structural properties on the detection of polyphenols. AB - There is a huge interest in doped graphene and how doping can tune the material properties for the specific application. It was recently demonstrated that the effect of doping can have different influence on the electrochemical detection of electroactive probes, depending on the analysed probe, on the structural characteristics of the graphene materials and on the type and amount of heteroatom used for the doping. In this work we wanted to investigate the effect of doping on graphene materials used as platform for the detection of catechin, a standard probe which is commonly used for the measurement of polyphenols in food and beverages. To this aim we compared undoped graphene with boron-doped graphene and nitrogen doped graphene platforms for the electrochemical detection of standard catechin oxidation. Finally, the material providing the best electrochemical performance was employed for the analysis of real samples. We found that the undoped graphene, possessing lower amount of oxygen functionalities, higher density of defects and larger electroactive surface area provided the best electroanalytical performance for the determination of catechin in commercial beer samples. Our findings are important for the development of novel graphene platforms for the electrochemical assessment of food quality. PMID- 26861508 TI - Onset and duration of transitions into Greenland Interstadials 15.2 and 14 in northern China constrained by an annually laminated stalagmite. AB - The onset and duration of abrupt transitions into Dansgaard-Oeschger (DO) events can be studied in detail in Greenland ice cores given the excellent relative uncertainty of its lamina-counting chronology. For other geological archives, however, the shorter intervals are not determined accurately due to lack of clear annual lamina. Here, we present an oxygen isotope record of a stalagmite with well-developed annual lamina from Xinglong Cave, northern China, covering DO 15 and 14. Except for the absence of Greenland Interstadial (GIS) 15.1, the pattern of this record strongly resembles that of Greenland ice cores on millennial scales as well as the detailed centennial-scale cooling excursions within GIS 14. Additionally, the transitions into GIS 15.2 and 14, constrained by lamina counting, lasted 74 and 27 yr, respectively, both of which are in excellent agreement with that of the NGRIP record on the GICC05 timescales (100 +/- 6 and 20 +/- 1 yr, respectively). The close coupling of abrupt climatic oscillations on millennial to decadal scales between Greenland and northern China implies a rapid atmospheric teleconnection between the North Atlantic and the East Asian Summer Monsoon regions, probably via the westerlies. PMID- 26861509 TI - Nanocaged enzymes with enhanced catalytic activity and increased stability against protease digestion. AB - Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a systematic study of the impact of both encapsulation and proximal polyanionic surfaces on a set of common metabolic enzymes. Activity assays at both bulk and single-molecule levels demonstrate increased substrate turnover numbers for DNA nanocage-encapsulated enzymes. Unexpectedly, we observe a significant inverse correlation between the size of a protein and its activity enhancement. This effect is consistent with a model wherein distal polyanionic surfaces of the nanocage enhance the stability of active enzyme conformations through the action of a strongly bound hydration layer. We further show that DNA nanocages protect encapsulated enzymes against proteases, demonstrating their practical utility in functional biomaterials and biotechnology. PMID- 26861513 TI - Recurrent Visual Electronic Hand Hygiene Reminders in the Anesthesia Work Area. PMID- 26861510 TI - Obstructive Sleep Apnea and the Subsequent Risk of Chronic Rhinosinusitis: A Population-Based Study. AB - The relationship between obstructive sleep apnea (OSA) and chronic rhinosinusitis (CRS) still remains unclear. This retrospective cohort study aimed to investigate the relationship between OSA and subsequent CRS using a population-based dataset. The study used data from the Taiwan Longitudinal Health Insurance Database 2005. We selected 971 patients with OSA for the study cohort and 4855 patients without OSA for the comparison cohort. Each patient was tracked for 5 years to determine those who were subsequently diagnosed with CRS. Stratified Cox proportional hazard regression analyses were performed to examine the association of OSA with subsequent CRS. The results revealed that 161 (2.76%) of the total sampled patients were subsequently diagnosed with CRS. Subsequent incidences of CRS were found in 64 (6.59%) patients with OSA and 97 (2.00%) patients without OSA. The adjusted hazard ratio (HR) of subsequent CRS for patients with OSA was 3.18 (95% confidence interval: 2.27~4.45) compared to those without OSA. Furthermore, the HR for CRS was similar for subjects with OSA for both genders (with an adjusted HR of 3.44 for males and 2.63 for females). We concluded that patients with OSA had a higher risk of subsequent CRS compared to patients without OSA regardless of sex. PMID- 26861512 TI - Morphological Changes of Cortical and Hippocampal Neurons after Treatment with VEGF and Bevacizumab. AB - AIMS: Vascular endothelial growth factor (VEGF) is a hallmark of glioblastoma multiforme (GBM) and plays an important role in brain development and function. Recently, it has been reported that treatment of GBM patients with bevacizumab, an anti-VEGF antibody, may cause a decline in neurocognitive function and compromise quality of life. Therefore, we investigated the effects of VEGF and bevacizumab on the morphology and on survival of neurons and glial cells. METHODS: Dissociated cortical and hippocampal cell cultures of juvenile rats were treated with VEGF, bevacizumab, and VEGF + bevacizumab. Neuronal and glial cell viability was analyzed, and the morphology of neurons was objectified by morphometric analysis. RESULTS: In cortical cultures, bevacizumab significantly decreased the number of neurons after 20 days and the number of glial cells subsequent 30 days. Additionally, an increase in the dendritic length of cortical neurons was obvious after 10 days of incubation with bevacizumab, but returned to control level after 30 days. In hippocampal cultures, cell viability was not affected by bevacizumab; however, dendritic length increased at day 10, but decreased after long-term treatment. CONCLUSION: Therefore, bevacizumab obviously has a cytotoxic effect in cortical cultures and decreases the dendritic length in hippocampal neurons after long-term treatment. PMID- 26861514 TI - Neuroprotective effects of metformin against Abeta-mediated inhibition of long term potentiation in rats fed a high-fat diet. AB - Metformin (Met) is used to treat neurodegenerative disorders such as Alzheimer's disease (AD). Conversely, high-fat diets (HFD) have been shown to increase AD risk. In this study, we investigated the neuroprotective effects of Met on beta amyloid (Abeta)-induced impairments in hippocampal synaptic plasticity in AD model rats that were fed a HFD. In this study, 32 adult male Wistar rats were randomly assigned to four groups: group I (control group, regular diet); group II (HFD+vehicle); group III (HFD+Abeta); or group IV (Met+HFD+Abeta). Rats fed a HFD were injected with Abeta to induce AD, allowed to recover, and treated with Met for 8 weeks. The rats were then anesthetized with intraperitoneal injections of urethane and placed in a stereotaxic apparatus for surgery, electrode implantation, and field potential recording. In vivo electrophysiological recordings were then performed to measure population spike (PS) amplitude and excitatory postsynaptic potential (EPSP) slope in the hippocampal dentate gyrus. Long-term potentiation (LTP) was induced by high-frequency stimulation of the perforant pathway. Blood samples were then collected to measure plasma levels of triglycerides, low-density lipoproteins, very low-density lipoprotein, and cholesterol. After induction of LTP, PS amplitude and EPSP slope were significantly decreased in Abeta-injected rats fed a HFD compared to vehicle injected animals or untreated animals that were fed a normal diet. Met treatment of Abeta-injected rats significantly attenuated these decreases, suggesting that Met decreased the effects of Abeta on LTP. These findings suggest that Met treatment is neuroprotective against the detrimental effects of Abeta and HFDs on hippocampal synaptic plasticity. PMID- 26861516 TI - Infantile Hemangioma: A Product of In Utero Implantation From the Placenta to the Skin: A Possible Door to the Future. PMID- 26861515 TI - Contemporary utilization and safety outcomes of catheter ablation of atrial flutter in the United States: Analysis of 89,638 procedures. AB - BACKGROUND: Atrial flutter (AFL) ablation has been increasingly offered as first line therapy and safely performed over the last decades. However, limited data exist regarding current utilization and trends in adverse outcomes arising from this procedure. OBJECTIVE: The aim of our study was to examine the frequency of adverse events attributable to AFL ablation and influence of hospital volume on safety outcomes. METHODS: Data were obtained from the Nationwide Inpatient Sample, the largest all-payer inpatient dataset in the United States. Patients with AFL who underwent catheter ablation from 2000 to 2011 were identified using ICD-9 codes. In-hospital death and common complications were identified, including cardiac perforation and tamponade, pneumothorax, stroke, transient ischemic attack, and vascular access complications. RESULTS: A total of 89,638 AFL patients were treated with catheter ablation during our study period. Total number of ablations performed increased by 154% from 2000 to 2011. The in hospital mortality rate was 0.17% and the overall complication rate was 3.17%. Cardiac complications (1.44%) were the most frequent, followed by respiratory (0.88%), vascular (0.78%), and neurological complications (0.05%). Low hospital volume (<50 procedures/year) was significantly associated with increased adverse outcomes. Overall frequency of complications per 100 ablation procedures increased from 2.86 in 2000 to 5.39 in 2011 (P < .001). CONCLUSIONS: The overall complication rate was 3.17% in patients undergoing AFL ablation. There was a significant association between low hospital volume and increased adverse outcomes. This suggests a need for future research into identifying the safety measures in AFL ablations and instituting appropriate interventions to improve overall AFL ablation outcomes. PMID- 26861518 TI - Topical Timolol: A Novel Approach in Infantile Hemangioma. AB - Infantile hemangioma is the most common benign vascular tumor of childhood that has a tendency for spontaneous involution. The aim of this study was to evaluate the efficacy of topical timolol maleate in the treatment of superficial infantile hemangioma and associated side effects during the course of treatment. Four boys and five girls with a median age of 5 months were reviewed at 2-week intervals for a period of 16 weeks. A decrease in size, color, and consistency were noted. Adverse effects caused by timolol maleate were noted and managed. Of nine cases, two patients showed excellent response, five showed good response, one showed partial response, and one had poor response. Topical timolol maleate is safe and effective in the treatment of infantile hemangioma. PMID- 26861517 TI - Electroporation as a New Treatment Modality for Melanoma and Other Cancers: The "Guilty Bystander" Hypothesis. PMID- 26861519 TI - Congenital Malalignment of the Great Toenail. AB - Congenital malalignment of the great toenail (CMA) is a disorder of the anatomic orientation of the ungual apparatus, in which the longitudinal axis of the nail plate is not parallel with the axis of the distal phalanx but is deflected sideways. This disorder is understood to arise from multiple factors. Although many theories have been proposed about its origin, its pathogenesis is not fully known. Besides the cosmetic impact, this disorder causes such problems in the medium and long term as onychocryptosis and difficulty in motion. Some cases may regress spontaneously, although persistent cases may require a specialized surgical approach. Congenital malalignment of the great toenail is poorly understood and described medical condition that is often treated incorrectly; thus, reviewing the subject is important. A symptombased clinical classification system is proposed to guide diagnosis and treatment modality decisions. PMID- 26861520 TI - Use of an Interferon-gamma Release Assay in the Detection of Latent Tuberculosis in Dermatology: A Descriptive Analysis. AB - With the increasing use of biologic therapy in psoriasis, it is becoming more important to identify and treat latent tuberculosis (TB) infection (LTBI). Tuberculin skin test (TST) has been traditionally used to detect LTBI, but interferon-gamma release assays (IGRAs), such as the T-SPOT.TB test (T-Spot), are increasingly being used in its place. The indications and results of 51 T-Spot tests performed at the National Skin Centre in Singapore between 2008 and 2010 were analyzed and compared with TST results, decision on LTBI treatment, and previous use of immunosuppressants. T-Spot was most commonly performed as part of a prebiologic workup in patients with psoriasis. A total of 14 (27.5%) results were positive, and no patients had features of active TB. Ten of these patients also underwent TST, five of whom had negative TST results. Six patients (11.8%) had equivocal results with T-Spot test. This study shows poor concordance between T-Spot test and TST. A high incidence of equivocal results in IGRA may limit the utility of the T-Spot test. PMID- 26861521 TI - Guidelines for the Topical Treatment of Psoriasis Vulgaris in the Levant and Iraq Area. AB - Psoriasis vulgaris is a common chronic, inflammatory, multisystem disorder that affects approximately 1.5% to 3.4% of the population in the Middle East. The disease has an impact on the quality of life in a significant number of affected patients. The majority of patients (approximately 70%) have mild to moderate psoriasis that is manageable with topical agents, which generally show a high efficacy to safety ratio. Topical agents can be used alone when treating patients with limited disease or may be used as adjunctive therapy for patients with more extensive psoriasis undergoing systemic treatment. Treatment should also be customized to meet individual patients' needs. To optimize the topical treatment of psoriasis in the Levant and Iraq area, dermatology experts from Iraq, Jordan, Lebanon, Palestine, and Syria met and initiated a project to develop guidelines and recommendations for the topical management of psoriasis. The guidelines are based on literature evidence and experts' opinions. We present recommendations for the use of topical corticosteroids, vitamin D analogues, calcineurin inhibitors, tazarotene, salicylic acid, anthralin, and coal tar, as well as combination therapy, based on their efficacy and safety profiles. PMID- 26861523 TI - Oral Mucosal Lesions: Oral Lichen Planus and Lichenoid Tissue Reaction/Interface Dermatitis-Part II. AB - In order to succinctly interpret the clinical undertones of oral lichen planus and lichenoid tissue reaction/interface dermatitis, the well-recognized oral mucosal lesions, it is mandatory to comprehend oral cavity biology in the right perspective, the clinical connotations of which have been highlighted in perspective to facilitate diagnosis. In addition, a focus is formed on systemic association. Additionally, the imperative of salient histopathology in the diagnosis is emphasized for instant reference. PMID- 26861522 TI - Trichotillomania: Demographic and Clinical Features From a Nationally Representative US Sample. AB - Trichotillomania (TTM) is a psychodermatologic disorder that is typically first seen in the dermatology clinic. There are no reported studies of TTM from nationally representative samples. The authors examined epidemiologic and clinical characteristics of an estimated 695,588+/-136,456 (unweighted count = 89) patient visits with physician-diagnosed TTM (using International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 312.39) from a nationally representative US sample. An estimated 20.6%+/-7.4% visits for TTM were by patients 12 years and younger and demonstrated no sex difference (P=.52). Overall, TTM patients were younger (mean age: 24.01+/-3.09 years) (P<.001) and more likely to be female (80.3%+/-6.2%) (P=.003). These demographic findings are consistent with standard diagnostic criteria for TTM (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition). There were no racial (white vs nonwhite) differences in TTM frequency. Psychiatric disorders were seen in 75.5%+/-9.1% of TTM patient visits, with depressive disorder being the most common comorbidity (37.8%+/-9.5%) and selective serotonin reuptake inhibitor antidepressants the most commonly (50.6%+/-9.7%) used medication. These findings highlight the importance of psychiatric comorbidity in TTM. PMID- 26861524 TI - A Wolf in Fox's Clothing: Aggressive Skin Cancers Posing as Less Aggressive Cancers. PMID- 26861525 TI - OPDIVO (Nivolumab). PMID- 26861526 TI - Should Moderately Atypical Dysplastic Nevi Be Re-excised? Follow the Yellow Brick Road! PMID- 26861527 TI - Eruptive Syringomas in Pigmented Skin. PMID- 26861528 TI - Here Chickie, Chickie: Chikungunya Has Arrived. PMID- 26861529 TI - Posttraumatic Onychoheterotopia: A Report of Two Cases. AB - Case 1: A 35-year-old otherwise healthy man presented to us with ectopic nail growth over the palmar aspect of the middle finger of the right hand for the past 9 to 10 months. His history was conspicuous for trauma to the right hand in which his index finger was amputated along with avulsion of the nail plate and laceration of the middle finger. Two months later, the nail grew back normally, together with an asymptomatic, ectopic nail on the palmar aspect of the same finger 1 cm proximal to the fingertip (Figure 1). The ectopic nail lacked the luster of a normal nail and was oriented vertically. The patient had to clip it regularly like the other nails. X-ray findings of the hand were normal. The quality of life of the patient was assessed using the Dermatology Life Quality Index (DLQI), with a score of 0. The patient refused surgical excision of the ectopic nail because it was asymptomatic. PMID- 26861530 TI - Curative Electrochemotherapy in Lentigo Maligna Melanoma. PMID- 26861531 TI - Efficacy of a Single Daily Dose of Levofloxacin in Gram-Negative Folliculitis Complicating Acne Vulgaris. PMID- 26861532 TI - Unusual Presentation of Acanthosis Nigricans Associated With Metabolic Syndrome. PMID- 26861534 TI - Dermatopathology. PMID- 26861533 TI - Hydroxychloroquine de Novo-Induced Psoriasis in a Patient With Lichen Planus Pigmentosus. PMID- 26861535 TI - Longitudinal association between cognitive performance and obsessive-compulsive symptoms in patients with psychosis and unaffected siblings. AB - OBJECTIVE: Obsessive-compulsive symptoms (OCS) frequently occur in psychotic disorders. Cross-sectional associations between OCS and cognitive impairment have led to different causal explanations. Whereas one assumes that higher cognitive impairment reflects a risk factor for psychotic patients to develop OCS, another suggests that deficits reflect a consequence of OCS. This study investigated the longitudinal interrelation between OCS and cognitive functioning. METHOD: Baseline and follow-up data from 622 patients and 670 un-affected siblings from the 'Genetic Risk and Outcome in Psychosis' study were analyzed. Participants were allocated to groups according to the presence or absence of OCS at assessments and compared on several cognitive domains. RESULTS: Cross-sectional comparisons revealed no group differences in cognitive performance. Longitudinal analyses comparing the groups with changes in OCS revealed one significant group effect with more problems in set-shifting abilities in patient who reported OCS development at follow-up. Significant time and interaction effects were mainly due to improvement in immediate verbal recall and digit-symbol coding in patients and siblings who reported remission of OCS. CONCLUSION: Although insight into causality needs further exploration, our results do not confirm the hypothesis of pre-existing cognitive risk constellations. Findings suggest that remission of comorbid OCS results in improved immediate verbal recall and processing speed. PMID- 26861537 TI - Theoretical study of carbon-based tips for scanning tunnelling microscopy. AB - Motivated by recent experiments, we present here a detailed theoretical analysis of the use of carbon-based conductive tips in scanning tunnelling microscopy. In particular, we employ ab initio methods based on density functional theory to explore a graphitic, an amorphous carbon and two diamond-like tips for imaging with a scanning tunnelling microscope (STM), and we compare them with standard metallic tips made of gold and tungsten. We investigate the performance of these tips in terms of the corrugation of the STM images acquired when scanning a single graphene sheet. Moreover, we analyse the impact of the tip-sample distance and show that it plays a fundamental role in the resolution and symmetry of the STM images. We also explore in depth how the adsorption of single atoms and molecules in the tip apexes modifies the STM images and demonstrate that, in general, it leads to an improved image resolution. The ensemble of our results provides strong evidence that carbon-based tips can significantly improve the resolution of STM images, as compared to more standard metallic tips, which may open a new line of research in scanning tunnelling microscopy. PMID- 26861536 TI - A 20-year retrospective cohort study of TB infection among the Hill-tribe HIV/AIDS populations, Thailand. AB - BACKGROUND: A retrospective cohort study was conducted to determine the situation, trend, and factors associated with TB infection, and factors related to the life status among the HIV/AIDS Hill-tribe in Northern Thailand. Hill-tribe people have been migrating to and formed settlements along the Thai border areas for many decades. There are now having 1.6 million people of 6 different groups Akha, Lahu, Lisu, Hmong, Yao and Keren-each with a specific culture, language and lifestyle. The Hill-tribe becomes a new vulnerable of HIV and TB infections in Thailand. METHODS: A systematic data-reviewing approach was used to identify the information from the rosters of ARV clinics, OPD cards, and laboratory reports from 16 hospitals in Chiang Rai Province, Thailand. The data were collected from the first reported HIV/AIDS case of the Hill-tribe to the end of 2010. A chi square test and logistic regression models were used to identify associations at the significance level of alpha = 0.05. RESULTS: A total of 3,130 cases were included in the study. The majority of patients were Akha (46.0 %) followed by Lahu (19.7 %), 54.6 % were males, 44.6 % were 26-35 years old. The major risk factor of HIV infection was sexual intercourse (93.1 %); 23.9 % were still alive at the date of data collection, 30.7 % were diagnosed with pulmonary TB. The Akha Hill-tribe HIV/AIDS individuals had a greater chance of TB infection than did Yao individuals with ORadj = 1.50 (95 % CI = 1.01-1.92). Females had a greater chance of TB infection than males with ORadj = 1.33 (95 % CI = 1.11-1.59); being classified as HIV and AIDS groups had a greater chance of TB infection than those asymptomatic group with ORadj = 11.59 (95 % CI = 7.19-18.71), and ORadj = 1.71 (95 % CI = 1.03-2.87); and not having received the ARV group had a greater chance of TB infection than those who having received the ARV group with ORadj = 2.59 (95 % CI = 2.09-3.22). The patients who had been diagnosed with HIV infection during 1990-1995 and 1996-2000 had less chance of TB infection than those who were diagnosed from 2006-2010, with ORadj = 0.04 (95 % CI = 0.01-0.14) and 0.11 (95 % CI = 0.07-0.17), respectively. Regarding life status; females had a better chance of being still alive at the date of data collection than being males with ORadj = 1.41 (95 % CI = 1.19-1.66). Those who had a defined route of transmission in the category of "mother-to-child" and "IDU" had a better chance of being still alive compared to those who contracted HIV from "sexual intercourse," with ORadj = 2.05 (95 % CI = 1.56-2.18), and ORadj = 8.45 (95 % CI = 1.55-46.13), respectively. CONCLUSIONS: Thailand needs to create a TB and HIV/AIDS surveillance system for Hill-tribe populations to determine the situation and trend and to develop an appropriate model for providing care at the earlier stage of HIV/AIDS infection to prevent later TB infection. PMID- 26861538 TI - Automation of a Nile red staining assay enables high throughput quantification of microalgal lipid production. AB - BACKGROUND: Within the context of microalgal lipid production for biofuels and bulk chemical applications, specialized higher throughput devices for small scale parallelized cultivation are expected to boost the time efficiency of phototrophic bioprocess development. However, the increasing number of possible experiments is directly coupled to the demand for lipid quantification protocols that enable reliably measuring large sets of samples within short time and that can deal with the reduced sample volume typically generated at screening scale. To meet these demands, a dye based assay was established using a liquid handling robot to provide reproducible high throughput quantification of lipids with minimized hands-on-time. RESULTS: Lipid production was monitored using the fluorescent dye Nile red with dimethyl sulfoxide as solvent facilitating dye permeation. The staining kinetics of cells at different concentrations and physiological states were investigated to successfully down-scale the assay to 96 well microtiter plates. Gravimetric calibration against a well-established extractive protocol enabled absolute quantification of intracellular lipids improving precision from +/-8 to +/-2 % on average. Implementation into an automated liquid handling platform allows for measuring up to 48 samples within 6.5 h, reducing hands-on-time to a third compared to manual operation. Moreover, it was shown that automation enhances accuracy and precision compared to manual preparation. It was revealed that established protocols relying on optical density or cell number for biomass adjustion prior to staining may suffer from errors due to significant changes of the cells' optical and physiological properties during cultivation. Alternatively, the biovolume was used as a measure for biomass concentration so that errors from morphological changes can be excluded. CONCLUSIONS: The newly established assay proved to be applicable for absolute quantification of algal lipids avoiding limitations of currently established protocols, namely biomass adjustment and limited throughput. Automation was shown to improve data reliability, as well as experimental throughput simultaneously minimizing the needed hands-on-time to a third. Thereby, the presented protocol meets the demands for the analysis of samples generated by the upcoming generation of devices for higher throughput phototrophic cultivation and thereby contributes to boosting the time efficiency for setting up algae lipid production processes. PMID- 26861539 TI - Sensitivity to reward and adolescents' unhealthy snacking and drinking behavior: the role of hedonic eating styles and availability. AB - BACKGROUND: Although previous research found a positive association between sensitivity to reward (SR) and adolescents' unhealthy snacking and drinking behavior, mechanisms explaining these associations remain to be explored. The present study will therefore examine whether the associations between SR and unhealthy snack and/or sugar-sweetened beverage (SSB) intake are mediated by external and/or emotional eating and if this mediation is moderated by availability at home or at school. METHODS: Cross-sectional data on snacking, availability of snacks at home and at school, SR (BAS drive scale) and external and emotional eating (Dutch eating behavior questionnaire) of Flemish adolescents (n = 1104, mean age = 14.7 +/- 0.8 years; 51 % boys; 18.0% overweight) in 20 schools spread across Flanders were collected. Moderated mediation analyses were conducted using generalized structural equation modeling in three steps: (1) direct association between SR and unhealthy snack or SSB intake, (2) mediation of either external or emotional eating and (3) interaction of home or school availability and emotional or external eating. RESULTS: Partial mediation of external eating (a*b = 0.69, p < 0.05) and of emotional eating (a*b = 0.92, p < 0.01) in the relation between SR and intake of unhealthy snacks was found (step 2). The relation between SR and SSB intake was not mediated by external or emotional eating (step 2). No moderation effects of home or school availability were found (step 3). CONCLUSION: Our findings indicate that the association between SR and the consumption of unhealthy snacks is partially explained by external and emotional eating in a population-based sample of adolescents irrespective of the home or school availability of these foods. PMID- 26861541 TI - Non-operated eye: open or taped shut? PMID- 26861540 TI - Relationship of left atrial global peak systolic strain with left ventricular diastolic dysfunction and brain natriuretic peptide level in end-stage renal disease patients with preserved left ventricular ejection fraction. AB - BACKGROUND: In end-stage renal disease patients with preserved LV ejection fraction undergoing chronic hemodialysis, we investigated the relationship of left atrial deformational parameters evaluated by two-dimensional speckle tracking imaging (2D-STI) with conventional echocardiographic diastolic dysfunction parameters and brain natriuretic peptide level. METHODS: The study group enrolled 30 patients treated with chronic hemodialysis three times weekly. Two-dimensional transthoracic echocardiography and Doppler studies were performed 44.93 (13.46) immediately before and after HD. All patients had preserved left ventricular ejection fraction. RESULTS: The mean age of patients was 44.93 +/- 13.46 years. The mean brain natriuretic peptide (BNP) value after HD was 221.56 +/- 197.79 pg/ml. BNP values were significantly higher before HD (p = 0.004), the anteroposterior diameter, area, and the volumes of the LA decreased significantly after HD. On the other hand, the left atrial ejection fraction (LAEF) and the peak LA strain during LV systole (LAGS) were found to be higher. Before HD, there were significant inverse correlations between LAGS and BNP levels (r = -0.482, p = 0.007), E/E' (r = -0.33, p = 0.049), LAVmax (r = -0.366, p = 0.047), and LAVmin (r = -0.579, p = 0.001). LAGS had a significant correlation with E' velocity (r = 0.557, p = 0.001) (Table 5) and LAEF (r = 0.58, p = 0.001). After HD, there were also significant correlations between LAGS and echocardiographic parameters of systolic and diastolic LV function. CONCLUSIONS: We observed that left atrium global peak systolic strain values decreased consistently with deteriorating systolic and diastolic function. Our results suggest that LAGS measurements may be helpful as a complimentary method to evaluate diastolic function. PMID- 26861542 TI - HIV risk and psychological distress among female entertainment workers in Cambodia: a cross-sectional study. AB - BACKGROUND: In Cambodia, there has been an increase in entertainment work as a result of the breakdown of the traditional brothel-based sex industry, presenting new challenges to addressing the health issues and needs of people working in the entertainment industry. This study aims to identify factors associated with psychological distress among female entertainment workers (FEWs) in Cambodia. METHODS: A two-stage cluster sampling method was used to randomly select 657 FEWs from entertainment establishments in Phnom Penh and Siem Reap in April and May 2014 for interviews using a structured questionnaire. Psychological distress was measured using the General Health Questionnaire (GHQ-12), and multivariate logistic regression analysis was conducted. RESULTS: Almost half of FEWs (43.2 %) had a higher level of psychological distress (GHQ-12 > 3), while 19.5 % reported having suicidal thoughts, and 7.3 % reported having attempted to commit suicide in the past 3 months. Controlling for confounding factors, women with a higher level of psychological distress were significantly more likely to rate their overall health (AOR = 1.88, 95 % CI 1.20 to 2.94) and quality of life (AOR = 2.39, 95 % CI 1.47 to 3.87) as poor. They were also significantly more likely to have suicidal ideation (AOR = 2.41, 95 % CI 1.45 to 3.76), rate their HIV risk as higher than the general population (AOR = 0.48, 95 % CI 0.31 to 0.74), have been forced to drink at work (AOR = 1.77, 95 % CI 1.19 to 2.62), have had clients requesting not to use a condom (AOR = 3.48, 95 % CI 1.14 to 10.62), be not able to find condoms when they needed it (AOR = 0.64, 95 % CI 0.45 to 0.93), have had a family member who said hurtful things to them during childhood (AOR = 1.84, 95 % CI 1.24 to 2.75), and have had a parent or guardian who had been physically abused (AOR = 1.93, 95 % CI 1.34 to 2.82). CONCLUSIONS: FEWs in Cambodia experience high levels of psychological distress, which likely stems from both past negative experiences and current working conditions. For women that are experiencing psychological distress, intervention programs aimed at improving mental health should specifically address substance use, condom availability and negotiation skills, and suicide risk. PMID- 26861545 TI - A limping child. PMID- 26861543 TI - Purkinje cell loss in essential tremor: Random sampling quantification and nearest neighbor analysis. AB - INTRODUCTION: Purkinje cell loss has been documented in some, although not all, postmortem studies of essential tremor. Hence, there is considerable controversy concerning the presence of Purkinje cell loss in this disease. To date, few studies have been performed. METHODS: Over the past 8 years, we have assembled 50 prospectively studied cases and 25 age-matched controls; none were reported in our previous large series of 33 essential tremor and 21 controls. In addition to methods used in previous studies, the current study used a random sampling approach to quantify Purkinje cells along the Purkinje cell layer with a mean of 217 sites examined in each specimen, allowing for extensive sampling of the Purkinje cell layer within the section. For the first time, we also quantified the distance between Purkinje cell bodies-a nearest neighbor analysis. RESULTS: In the Purkinje cell count data collected from fifteen 100 * fields, cases had lower counts than controls in all three counting criteria (cell bodies, nuclei, and nucleoli; all P < 0.001). Purkinje cell linear density was also lower in cases than controls (all P < 0.001). Purkinje cell linear density obtained by random sampling was similarly lower in cases than controls in all three counting criteria (cell bodies, nuclei, and nucleoli, all P <= 0.005). In agreement with the quantitative Purkinje cell counts, the mean distance from one Purkinje cell body to another Purkinje cell body along the Purkinje cell layer was greater in cases than controls (P = 0.002). CONCLUSIONS: These data provide support for the neurodegeneration of cerebellar Purkinje cells in essential tremor. PMID- 26861546 TI - The long-term fate of epistaxis patients with exposure to antithrombotic medication. AB - The goal of this study was to evaluate independent risk factors for long-term epistaxis recurrences and their severity. Individual retrospective cohort study 2b level of evidence. The medical information of 603 emergency epistaxis patients was acquired during a former study. This cohort has been contacted 6 years later by conventional mail and asked to answer a specific paper questionnaire. The following parameters were evaluated: recurrent epistaxis episodes, need for a surgical intervention to stop the recurrent bleeding, patient's history for hypertension and diabetes, intake of hemostasis impairing medication now and in the past. One hundred and six (106) patients were included in the study (35.8 % response rate). The mean observation period was 76.58 months. Almost half of the patients (41.5 % = 44/106) reported at least one recurrent epistaxis episode. Patients with exposure to VKA (vitamin K antagonists) showed significantly more frequently a recurrent epistaxis episode. The binary logistic regression confirmed the intake of VKA as an independent and significant risk factor with an odds ratio of 11.6. Every single patient who had to undergo a surgical intervention to stop a recurrent bleeding stated ASA (Acetylsalicylic Acid) intake. We provide evidence that the intake of a vitamin K antagonist is an independent long-term risk factor for recurrent epistaxis episodes. The intake of ASA is a risk factor for the severity of recurrent epistaxis with the increased need for a surgical intervention not only in a short- but also in a long-term perspective. LEVEL OF EVIDENCE: This prognostic investigation, designed as a combined prospective and retrospective cohort study, reaches level 2b level of evidence as it includes retrospective aspects. PMID- 26861544 TI - Combining targeted therapy with immunotherapy. Can 1+1 equal more than 2? AB - Targeted therapies have induced high response rates and improved survival in patients with cancer. However, the long-term effectiveness of targeted therapies has been limited by the development of acquired resistance in the majority of patients. On the other hand, the modern immunotherapy strategies have been associated with durable responses but in limited number of patients. Accordingly, research efforts have been focused on examining the effects of combinations of targeted therapy and immunotherapy in several different histological subtypes of cancer. There has been accumulated evidence to suggest that targeted therapy can induce immune effects in the tumor cells, the host immune system, and the tumor microenvironment. Subsequently, clinical trials have been designed to examine the efficacy of combining immune checkpoint blockade or adoptive cell transfer with tyrosine kinase inhibitors, HER family blockade, anti-angiogenic agents, histone deacetylase inhibitors, and cancer stem cell inhibitors. To date, the combination of immunotherapy with targeted therapy has demonstrated potential as a cancer treatment strategy, but further optimizations are required and caution must be taken to avoid toxicity. The current review summarizes existing evidence and provides rationale supporting the use of combined targeted and immune-therapy approaches in patients with different types of cancer. PMID- 26861547 TI - Effect of continuous positive airway pressure on arterial stiffness in patients with obstructive sleep apnea and hypertension: a meta-analysis. AB - Arterial stiffness has been recognized as a predictor of cardiovascular and all cause mortality in hypertensive patients. However, the impact of continuous positive airway pressure (CPAP) on arterial stiffness in patients with OSA and hypertension remains inconclusive. We performed a meta-analysis to determine whether effective CPAP therapy could decrease arterial stiffness. Two reviewers independently searched PubMed, Embase, Web of Science and Cochrane Library prior to March 5, 2015. Information on characteristics of subjects, study design and pre- and post-CPAP treatment of arterial stiffness was extracted for analysis. Standardized mean difference (SMD) was used to analyze the summary estimates for CPAP therapy. Three articles with 186 patients were included in this meta analysis, including two observational studies and one randomized controlled study. The meta-analysis showed that CPAP was associated with a statistically significant decrease in arterial stiffness in patients with OSA and hypertension (SMD = -0.65, 95 % confidence interval (CI) = -1.14 to -0.16, z = 2.60, p = 0.009). Our meta-analysis suggested that CPAP among OSA and hypertensive patients was significantly associated with a decrease in arterial stiffness. Further prospective large-scale multicenter RCTs are needed to explore the precise impact of CPAP therapy on arterial stiffness in patients with OSA and hypertension. PMID- 26861548 TI - Classification of parotidectomies: a proposal of the European Salivary Gland Society. AB - The objective of this study is to provide a comprehensive classification system for parotidectomy operations. Data sources include Medline publications, author's experience, and consensus round table at the Third European Salivary Gland Society (ESGS) Meeting. The Medline database was searched with the term "parotidectomy" and "definition". The various definitions of parotidectomy procedures and parotid gland subdivisions extracted. Previous classification systems re-examined and a new classification proposed by a consensus. The ESGS proposes to subdivide the parotid parenchyma in five levels: I (lateral superior), II (lateral inferior), III (deep inferior), IV (deep superior), V (accessory). A new classification is proposed where the type of resection is divided into formal parotidectomy with facial nerve dissection and extracapsular dissection. Parotidectomies are further classified according to the levels removed, as well as the extra-parotid structures ablated. A new classification of parotidectomy procedures is proposed. PMID- 26861549 TI - Overexpressed transcription factor FOXM1 contributes to the progression of colorectal cancer. AB - Forkhead box M1 (FOXM1) is a characteristic proliferation-associated transcription factor, which is overexpressed in various types of human cancer. The aim of the present study was to determine the expression of FOXM1 in a large collection of colorectal cancer (CRC) samples. Between March 2012 and January 2014, 96 patients with histologically diagnosed CRC were recruited into the current study. Using immunohistochemistry, reverse transcription-quantitative polymerase chain reaction and western blotting, mRNA and protein expression levels of FOXM1 in CRC tissue samples were determined. The function of FOXM1 in the CRC cells was evaluated by small interfering RNA-mediated depletion of FOXM1, followed by analyses of cell proliferation and invasion. High levels of staining for FOXM1 were observed in significantly more CRC tissue samples: 85.42% (82/96) of CRC tissue samples compared with 18.75% (18/96) of adjacent normal mucosa tissue samples. Silencing FOXM1 inhibited the proliferation of LoVo cells, which express a relatively high level of FOXM1, and the invasion and migration of LoVo cells were also markedly suppressed. The data from the present study suggested that the pathogenesis of human CRC may be mediated by FOXM1, and that FOXM1 inhibition may provide a promising therapeutic strategy for CRC. PMID- 26861551 TI - Discovery of 6-Amino-2-{[(1S)-1-methylbutyl]oxy}-9-[5-(1-piperidinyl)pentyl]-7,9 dihydro-8H-purin-8-one (GSK2245035), a Highly Potent and Selective Intranasal Toll-Like Receptor 7 Agonist for the Treatment of Asthma. AB - Induction of IFNalpha in the upper airways via activation of TLR7 represents a novel immunomodulatory approach to the treatment of allergic asthma. Exploration of 8-oxoadenine derivatives bearing saturated oxygen or nitrogen heterocycles in the N-9 substituent has revealed a remarkable selective enhancement in IFNalpha inducing potency in the nitrogen series. Further potency enhancement was achieved with the novel (S)-pentyloxy substitution at C-2 leading to the selection of GSK2245035 (32) as an intranasal development candidate. In human cell cultures, compound 32 resulted in suppression of Th2 cytokine responses to allergens, while in vivo intranasal administration at very low doses led to local upregulation of TLR7-mediated cytokines (IP-10). Target engagement was confirmed in humans following single intranasal doses of 32 of >=20 ng, and reproducible pharmacological response was demonstrated following repeat intranasal dosing at weekly intervals. PMID- 26861552 TI - Clinical Significance of Circulating Tumor Microemboli as a Prognostic Marker in Patients with Pancreatic Ductal Adenocarcinoma. AB - BACKGROUND: Characterization of circulating tumor cells (CTCs) has been used to provide prognostic, predictive, and pharmacodynamic information in many different cancers. However, the clinical significance of CTCs and circulating tumor microemboli (CTM) in patients with pancreatic ductal adenocarcinoma (PDAC) has yet to be determined. METHODS: In this prospective study, CTCs and CTM were enumerated in the peripheral blood of 63 patients with PDAC before treatment using anti-EpCAM (epithelial cell adhesion molecule)-conjugated supported lipid bilayer-coated microfluidic chips. Associations of CTCs and CTM with patients' clinical factors and prognosis were determined. RESULTS: CTCs were abundant [mean (SD), 70.2 (107.6)] and present in 81% (51 of 63) of patients with PDAC. CTM were present in 81% (51 of 63) of patients with mean (SD) 29.7 (1101.4). CTM was an independent prognostic factor of overall survival (OS) and progression free survival (PFS). Patients were stratified into unfavorable and favorable CTM groups on the basis of CTM more or less than 30 per 2 mL blood, respectively. Patients with baseline unfavorable CTM, compared with patients with favorable CTM, had shorter PFS (2.7 vs 12.1 months; P < 0.0001) and OS (6.4 vs 19.8 months; P < 0.0001). Differences persisted if we stratified patients into early and advanced diseases. The number of CTM before treatment was an independent predictor of PFS and OS after adjustment for clinically significant factors. CONCLUSIONS: The number of CTM, instead of CTCs, before treatment is an independent predictor of PFS and OS in patients with PDAC. PMID- 26861550 TI - Preclinical models of muscle spasticity: valuable tools in the development of novel treatment for neurological diseases and conditions. AB - Poor validity of preclinical animal models is one of the most commonly discussed explanations for the failures to develop novel drugs in general and in neuroscience in particular. However, there are several areas of neuroscience such as injury-induced spasticity where etiological factor can be adequately recreated and models can focus on specific pathophysiological mechanisms that likely contribute to spasticity syndrome in humans (such as motoneuron hyperexcitability and spinal hyperreflexia). Methods used to study spasticity in preclinical models are expected to have a high translational value (e.g., electromyogram (EMG)-based electrophysiological tools) and can efficiently assist clinical development programs. However, validation of these models is not complete yet. First, true predictive validity of these models is not established as clinically efficacious drugs have been used to reverse validate preclinical models while newly discovered mechanisms effective in preclinical models are yet to be fully explored in humans (e.g., 5-HT2C receptor inverse agonists, fatty acid amid hydrolase inhibitors). Second, further efforts need to be invested into cross laboratory validation of study protocols and tools, adherence to the highest quality standards (blinding, randomization, pre-specified study endpoints, etc.), and systematic efforts to replicate key sets of data. These appear to be readily achievable tasks that will enable development not only of symptomatic but also of disease-modifying therapy of spasticity, an area that seems to be currently not in focus of research efforts. PMID- 26861554 TI - The Suicidal Risks and Treatments, Seek Medications from Multi-disciplinary. AB - Suicide events and episodes are serious human psychiatric disorders affected by a great number of different environmental/economic factors, early trauma/abuse, human bad living habits, human genomic properties and drug intervention decisions. In order to improve antidepressant therapeutics in clinics, the relationships between efficacy and toxicities of antidepressants have to be considered fundamentally. Since the occurrences and risks of suicidal events or episodes come from interplay between insiders (chemical/genomic/bioinformatics factors) and outsiders (economic/social/ previous trauma conditions and so on), new perspectives and scientific studies must be implemented for revealing these interrelated factors step-by-step and updating therapeutics in human beings. New paradigms and clinical strategies -joint-expert groups and clinical practices (a psychiatrist with other field specialists) should be established for individual patients in future. Thus can some improvements in clinical trials be achieved in a long run? PMID- 26861553 TI - Classifying Germline Sequence Variants in the Era of Next-Generation Sequencing. PMID- 26861555 TI - S-system-based analysis of the robust properties common to many biochemical network models. AB - Robustness is a key feature to characterize the adaptation of organisms to changes in their internal and external environments. A broad range of kinetic or dynamic models of biochemical systems have been developed. Robustness analyses are attractive for exploring some common properties of many biochemical models. To reveal such features, we transform different types of mathematical equations into a standard or intelligible formula and use the multiple parameter sensitivity (MPS) to identify some factors critically responsible for the total robustness to many perturbations. The MPS would be determined by the top quarter of the highly sensitive parameters rather than the single parameter with the maximum sensitivity. The MPS did not show any correlation to the network size. The MPS is closely related to the standard deviation of the sensitivity profile. A decrease in the standard deviation enhanced the total robustness, which shows the hallmark of distributed robustness that many factors (pathways) involve the total robustness. PMID- 26861556 TI - Elucidating the binding efficacy of beta-galactosidase on graphene by docking approach and its potential application in galacto-oligosaccharide production. AB - Herein, we propose the synthesis and characterization of graphene for the immobilization of beta-galactosidase for improved galacto-oligosaccharide (GOS) production. The size of synthesized graphene was observed to be 25 nm by TEM analysis while interaction of enzyme with the nanosupport was observed by FTIR spectroscopy. Docking was obtained using molecular docking program Dock v.6.5 while the visual analyses and illustration of protein-ligand complex were investigated by utilizing chimera v.1.6.2 and PyMOL v.1.3 softwares. Immobilized beta-galactosidase (IbetaG) showed improved stability against various physical and chemical denaturants. Km of IbetaG was increased to 6.41 mM as compared to 2.38 mM of soluble enzyme without bringing significant change in Vmax value. Maximum GOS content also registered an increase in lactose conversion. The maximum GOS production was achieved by immobilized enzyme at specific temperature and time. Hence, the developed nanosupport can be further exploited for developing a biosensor involving beta-galactosidase or for immobilization of other industrially/therapeutically important enzymes. PMID- 26861558 TI - A case of Bilateral Perisylvian Syndrome with reading disability. PMID- 26861559 TI - Can predictive coding explain repetition suppression? AB - While in earlier work various local or bottom-up neural mechanisms were proposed to give rise to repetition suppression (RS), current theories suggest that top down processes play a role in determining the repetition related reduction of the neural responses. In the current review we summarise those results, which support the role of these top-down processes, concentrating on the Bayesian models of predictive coding (PC). Such models assume that RS is related to the statistical probabilities of prior stimulus occurrences and to the future predictability of these stimuli. Here we review the current results that support or argue against this explanation. We point out that the heterogeneity of experimental manipulations that are thought to reflect predictive processes are likely to measure different processing steps, making their direct comparison difficult. In addition we emphasize the importance of identifying these sub-processes and clarifying their role in explaining RS. Finally, we propose a two-stage model for explaining the relationships of repetition and expectation phenomena in the human cortex. PMID- 26861557 TI - Repetition suppression and its contextual determinants in predictive coding. AB - This paper presents a review of theoretical and empirical work on repetition suppression in the context of predictive coding. Predictive coding is a neurobiologically plausible scheme explaining how biological systems might perform perceptual inference and learning. From this perspective, repetition suppression is a manifestation of minimising prediction error through adaptive changes in predictions about the content and precision of sensory inputs. Simulations of artificial neural hierarchies provide a principled way of understanding how repetition suppression - at different time scales - can be explained in terms of inference and learning implemented under predictive coding. This formulation of repetition suppression is supported by results of numerous empirical studies of repetition suppression and its contextual determinants. PMID- 26861560 TI - Long-noncoding RNAs in basal cell carcinoma. AB - Long noncoding RNAs (lncRNAs) are fundamental regulators of pre- and post transcriptional gene regulation. Over 35,000 different lncRNAs have been described with some of them being involved in cancer formation. The present study was initiated to describe differentially expressed lncRNAs in basal cell carcinoma (BCC). Patients with BCC (n = 6) were included in this study. Punch biopsies were harvested from the tumor center and nonlesional epidermal skin (NLES, control, n = 6). Microarray-based lncRNA and mRNA expression profiles were identified through screening for 30,586 lncRNAs and 26,109 protein-coding transcripts (mRNAs). The microarray data were validated by RT-PCR in a second set of BCC versus control samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of mRNAs were performed to assess biologically relevant pathways. A total of 1851 lncRNAs were identified as being significantly up-regulated, whereas 2165 lncRNAs were identified as being significantly down-regulated compared to nonlesional skin (p < 0.05). Oncogenic and/or epidermis-specific lncRNAs, such as CASC15 or ANRIL, were among the differentially expressed sequences. GO analysis showed that the highest enriched GO targeted by up-regulated transcripts was "extracellular matrix." KEGG pathway analysis showed the highest enrichment scores in "Focal adhesion." BCC showed a significantly altered lncRNA and mRNA expression profile. Dysregulation of previously described lncRNAs may play a role in the molecular pathogenesis of BCC and should be subject of further analysis. PMID- 26861562 TI - The near field/far field model with constant application of chemical mass and exponentially decreasing emission of the mass applied. AB - The near field/far field (NF/FF) model is a contaminant dispersion construct that permits making airborne contaminant exposure estimates for an individual located close to an emission source. In the present analysis, chemical emission involves a constant mass rate of chemical application to surfaces, denoted I (mg/min), and an exponentially decreasing rate of emission of the chemical from the surfaces with rate constant alpha (min(-1)). The time-dependent emission rate function is: G(t), mg/min = I - I exp(- alphat), where time t is in minutes. The exact time dependent equations for the contaminant concentration in the NF and the FF are presented. These equations are used to revise a previous analysis of a study in which a penetrant liquid containing benzene was applied to parts on a work table in a test room. The previous analysis assumed that the benzene was applied as a bolus at the start of a 15-min use period, whereas the present analysis assumes the same total benzene mass was applied at a uniform rate over the 15-min use period, but with the same evaporation rate constant alpha. The new G(t) function leads to a lower 15-min time weighted average NF benzene concentration that better matches the experimental data. It is also shown that the exact equation for the NF concentration is well approximated by combining two well-mixed single zone equations. The approximation method is mathematically simpler and obviates the need to derive the exact NF equation. PMID- 26861561 TI - MicroRNA-130b promotes proliferation and EMT-induced metastasis via PTEN/p AKT/HIF-1alpha signaling. AB - Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths owing to its high rate of postoperative recurrence and metastasis. New research is continuously identifying novel metastasis-associated oncogenes and tumor suppressor genes. miRNAs are noncoding RNAs that regulate protein synthesis post translationally. miR-130b is one of several miRNAs involved in tumor metastasis. However, the role of miR-130b in HCC remains controversial. Here, we demonstrate that miR-130b is highly expressed in HCC and that it correlates with tumor number, vascular invasion, and TNM stage-important predictors of postoperative recurrence and metastases. Moreover, high levels of miR-130b predicted poor overall and disease-free survival of HCC patients, and in vitro and in vivo research revealed that knockdown or overexpression of miR-130b inhibited and promoted proliferation and metastasis of HCC cells, respectively. We identified PTEN as a direct functional target of miR-130b using miRNA databases and a dual luciferase report assay. Next, using a gain and loss assay and epithelial mesenchymal transition (EMT) relative assays, we show that miR-130b may promote proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1alpha signaling. Collectively, our data suggests that miR-130b may have prognostic value in HCC. Additionally, the miR-130b/PTEN/p-AKT/HIF-1alpha axis identified in this study provides novel insight into the mechanisms of HCC metastasis, which may facilitate the development of new therapeutics against HCC. PMID- 26861563 TI - Ritonavir Use in Human Immunodeficiency Virus-Positive Surgical Patients Is Not Associated with an Increase in Postoperative Critical Respiratory Events. AB - This study evaluated whether highly active antiretroviral therapy for human immunodeficiency virus (HIV) including ritonavir is independently associated with increased critical respiratory events after general anesthesia with opioid analgesia. The impact of ritonavir on hepatic microsomal enzymes was considered due to the effect of these enzymes on opioid metabolism. Medical records of over 1900 patients were reviewed, and those of 941 patients met inclusion criteria and were analyzed. Chronic treatment with ritonavir was not associated with critical respiratory events in HIV-positive patients. PMID- 26861564 TI - Delayed perforation after endoscopic band ligation for treatment of colonic diverticular bleeding. PMID- 26861565 TI - A review on the management of migraine in the Avicenna's Canon of Medicine. AB - Migraine is a common type of headache which has a deep history dating back thousands of years. Avicenna (980-1032), a Persian scholar, made a great contribution to neurology including headache and migraine. The aim of this study is to consider Avicenna's description about migraine (Shaghighe in Persian language) including definition, etiology and intervention. Also, his definition and treatment approaches were considered based on current concepts and findings. Although Avicenna believed in humoral theory and divided migraine into two categories, hot and cold, and suggested special treatments for them as well as general considerations, most of his definitions and explained pathologies are supported by current concepts of medicine. He believed that the migraine can result from bone of skull and also intra-parenchymal; or from skull underneath membrane (dura-mater); or reaching substances from the painful side or from outer vein and arteries (extra cranial); or from brain and meninges (pia-mater). Furthermore, current findings show most medicinal plants mentioned by Avicenna for the treatment of migraine can have potentially significant effects such as remedies which stop central and peripheral sensitization [anti-neuroinflammatory agents, decreasing nitric oxide level, cyclooxygenase (COX)-2 inhibitors], as well as serotonergics, neuroprotective agents and analgesics. PMID- 26861566 TI - Treatment of Adults with Lennox-Gastaut Syndrome: Further Analysis of Efficacy and Safety/Tolerability of Rufinamide. AB - INTRODUCTION: Management of Lennox-Gastaut syndrome (LGS) in adulthood can be particularly challenging. Published reports describing the use of rufinamide specifically in adult patients with LGS are scarce. A post hoc subgroup analysis of data from a phase III trial was conducted to investigate the efficacy and safety/tolerability of rufinamide in adults with LGS. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in patients with LGS, aged 4 years and above. During an 84-day, double-blind treatment period, patients received either adjunctive rufinamide therapy or placebo. Efficacy and safety/tolerability were assessed in a post hoc subgroup analysis of adult patients (>=18 years). Efficacy was assessed as change from baseline in 28-day seizure frequency, 50% responder rate, and seizure freedom rate; each calculated for total seizures and drop attacks. Safety/tolerability assessments included the evaluation of adverse events (AEs). RESULTS: Thirty-one adults aged 18-37 years with LGS received treatment with either rufinamide (n = 21) or placebo (n = 10). Three patients in the rufinamide group did not complete the trial. The median change from baseline in seizure frequency was -31.5% for rufinamide versus +22.1% for placebo (P = 0.008) for all seizures and -54.9% versus +21.7% (P = 0.002) for drop attacks. Responder rates were 33.3% for rufinamide versus 0% for placebo (P = 0.066) for all seizures and 57.1% versus 10.0% (P = 0.020) for drop attacks. No patient achieved freedom from all seizures but two rufinamide-treated patients (9.5%) became free of drop attacks. Overall, 71.4% of patients treated with rufinamide and 60.0% of patients treated with placebo experienced AEs; most commonly, somnolence (33.3% vs. 20.0%) and vomiting (19.0% vs. 0%). Most AEs were of mild or moderate intensity. CONCLUSION: Rufinamide demonstrated favorable efficacy and was generally well tolerated when used as adjunctive treatment for adults with LGS. FUNDING: Eisai. PMID- 26861567 TI - Subependymal giant cell astrocytoma (SEGA): a case report and review of the literature. AB - BACKGROUND: Subependymal giant cell astrocytoma is a rare tumor that occurs in the wall of the lateral ventricle and foramen of Monro and, rarely, in the third ventricle. It is one of the intracranial lesions found in tuberous sclerosis complex (which include subependymal nodules, cortical tubers, retinal astrocytoma and subependymal giant cell astrocytoma), but cases without such lesions have also been reported in the literature. It was described for the first time in 1908 by Vogt as part of the typical triad of tuberous sclerosis complex. At the 2012 Washington Consensus Conference, it was decided by the invited expert panel to document the definition of subependymal giant cell astrocytoma as a lesion at the caudothalamic groove with either a size of more than 1 cm in any direction or a subependymal lesion at any location that has shown serial growth on consecutive imaging regardless of size. Most subependymal giant cell astrocytomas will show avid enhancement after contrast administration; however, a growing subependymal lesion even in the absence of enhancement should be considered a subependymal giant cell astrocytoma. CASE PRESENTATION: We report a case of subependymal giant cell astrocytoma in a 10-year-old white girl, who had no clinical symptoms of tuberous sclerosis. A computed tomography scan revealed a voluminous mass in her perilateral ventricle. An extemporaneous examination was in favor of a benign ganglioglioma tumor. After fixation in 10 % neutral-buffered formalin, embedding in paraffin and staining with hematoxylin, eosin and safran, the definitive diagnosis was subependymal giant cell astrocytoma. CONCLUSIONS: Subependymal giant cell astrocytoma is a rare tumor of the central nervous system whose diagnosis is based on clinical, radiological, histological and immunohistochemical arguments. For its rarity, we must consider this diagnosis when faced with a mass near the foramen of Monro in the pediatric population even if there are no other features of tuberous sclerosis complex. PMID- 26861569 TI - Uptake and levels of the antibiotic berberine in individual dormant and germinating Clostridium difficile and Bacillus cereus spores as measured by laser tweezers Raman spectroscopy. AB - OBJECTIVES: Spores of Clostridium difficile and Bacillus cereus are major causes of nosocomial diarrhoea and foodborne disease. Our aim was to measure the dynamics of the uptake of the antibiotic berberine by individual germinating spores and the levels of berberine accumulated in germinated spores. METHODS: Laser tweezers Raman spectroscopy (LTRS) and differential interference contrast microscopy were used to measure levels of berberine accumulated in single germinating spores and to monitor berberine uptake and germination of individual C. difficile and B. cereus spores. RESULTS: MIC values of berberine for C. difficile and B. cereus spores were 640 and 256 mg/L, respectively. Levels of berberine accumulated at the berberine MICs in individual germinated spores were heterogeneous, with values of 17.1 +/- 5.4 and 12.7 +/- 5.5 g/L for C. difficile and B. cereus spores, respectively. These values were 25-50-fold higher than the MIC values. However, berberine did not affect the germination of C. difficile and B. cereus spores, but did block germinated spores' outgrowth. Berberine uptake kinetics were similar for these two kinds of spores. After the addition of germinants, berberine began to enter germinating spores at the time (Tlag) when rapid release of the spore core's large depot of the 1:1 chelate of Ca(2+) with dipicolinic acid began, and the level of berberine taken up was maximal shortly after spore cortex lysis was completed (Tlysis). CONCLUSIONS: LTRS can be used to measure uptake and levels of berberine in single cells. High levels of berberine can enter spores of C. difficile and B. cereus soon after germination is initiated, thus inhibiting spore outgrowth and minimizing hazards posed by germinated spores. PMID- 26861568 TI - Significance of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and prognostic nutrition index as preoperative predictors of early mortality after liver resection for huge (>=10 cm) hepatocellular carcinoma. AB - BACKGROUND: This study aimed to determine preoperative predictors of early (<1 year) mortality from disease recurrence after liver resection (LR) for huge (>=10 cm) HCC, with special emphasis on the importance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and prognostic nutrition index (PNI). METHODS: Between 2000 to 2013, 166 patients underwent LR for huge HCC. Optimal cut-offs for alpha fetoprotein (AFP), NLR, PLR, and PNI were determined by plotting the receiver operator curves (ROC) in predicting early mortality and utilizing the Youden index. RESULTS: The 30-day/in-hospital postoperative mortality rate was 4.2%. The 5-year overall survival (OS) and the 5-year recurrence-free survival (RFS) was 43% and 24%, respectively. Early mortality from disease recurrence occurred in 35 of 159 (22%) patients. Multivariate analyses demonstrated that tumor rupture and high AFP (>1,085 ng/ml) were independent preoperative predictors of early mortality after LR for HCC, and both a low PNI (<41) and high AFP were independent predictors of early mortality for non-ruptured HCC. In 51 patients who had none of these three factors, only four (7.8%) patients experienced early mortality from disease recurrence. CONCLUSIONS: Spontaneous rupture, high AFP, and low PNI were predictors of early mortality from disease recurrence after LR for huge HCC. J. Surg. Oncol. 2016;113:621-627. (c) 2016 Wiley Periodicals, Inc. PMID- 26861570 TI - In vivo emergence of ceftaroline resistance during therapy for MRSA vertebral osteomyelitis. PMID- 26861571 TI - Biphasic modulation of Wnt signaling supports efficient foregut endoderm formation from human pluripotent stem cells. AB - Pluripotent stem cells (embryonic stem cells and induced pluripotent stem cells) are of great promise in regenerative medicine, including molecular studies of disease mechanisms, if the affected cell type can be authentically generated during in vitro differentiation. Most existing protocols aim to mimic embryonic development steps by the supplementation of specific cytokines and small molecules, but the involved signaling pathways need further exploration. In this study, we investigated enhanced initial activation of Wnt signaling for definitive endoderm formation and subsequent rapid shutdown of Wnt signaling for proper foregut endoderm specification using 3 MUM CHIR99021 and 0.5 MUg/mL of secreted frizzled-related protein 5 (sFRP-5) for biphasic modulation of the Wnt pathway. The definitive endoderm and foregut endoderm differentiation capabilities of Wnt pathway-modulated cells were determined based on the expression levels of the endodermal transcription factors SOX17 and FOXA2 and those of the transcription activator GATA4 and the alpha-fetoprotein (AFP) gene, respectively. Furthermore, the resulting biphasic Wnt pathway modulation was investigated at the protein level by analyzing phosphorylation of glycogen synthase kinase 3 beta (GSK3beta) and beta-catenin. Finally, Wnt target gene expression was determined using an improved lentiviral reporter construct that enabled robust T-cell transcription factor 4 (TCF4)/lymphoid enhancer-binding factor 1 (LEF1)-mediated luciferase expression in differentiating pluripotent stem cells. In conclusion, we demonstrated robust, homogeneous, and efficient derivation of foregut endodermal cells by inducing a biphasic modulation of the Wnt signaling pathway. PMID- 26861572 TI - Introducing Twitter as an assessed component of the undergraduate nursing curriculum: case study. AB - AIMS: To ask: (i) is it feasible to include Twitter as an assessed element of the first-year nursing curriculum; (ii) how should it be introduced and assessed; and (iii) do students think it worthwhile and learn anything from its use? BACKGROUND: Nursing students need to use social media professionally, avoiding pitfalls but using learning opportunities. DESIGN: This case study (2014-2015) comprised: (i) pilot introduction of Digital Professionalism (including Twitter) with second- and third-year students; (ii) introduction and assessment with a first cohort of 450 first-year students. Based on feedback, methods were revised for; (iii) a second cohort of 97. METHODS: Students received a face-to-face lecture, two webinars, used chat rooms and were asked to create course Twitter accounts and were assessed on their use. RESULTS: Few second and third year students started optional Twitter use whereas nearly all first years used it. Most students (70.1% first, 88.0% second cohort) thought inclusion of Twitter was worthwhile. Changes from first to second cohort included better peer-peer support, more contextualization and more emphasis on nursing communities. More second cohort students learned from Twitter (44.4% vs. 70.8%) and used Twitter recently (43.3% vs. 81.6%). Students gained wider perspectives on nursing, better understanding of social media, 'being student nurses' and topics like health promotion. Students mostly followed not only online nursing communities but also patient organizations. CONCLUSION: Including Twitter as an assessed element for first-year nursing students was feasible, students think it worthwhile and other nursing schools should consider introducing it in the broader context of Digital Professionalism. PMID- 26861573 TI - HIV-1 Group O Genotypes and Phenotypes: Relationship to Fitness and Susceptibility to Antiretroviral Drugs. AB - Despite only 30,000 group O HIV-1 infections, a similar genetic diversity is observed among the O subgroups H (head) and T (tail) (previously described as subtypes A, B) as in the 9 group M subtypes (A-K). Group O isolates bearing a cysteine at reverse transcriptase (RT) position 181, predominantly the H strains are intrinsically resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, their susceptibility to newer antiretroviral drugs such as etravirine, maraviroc, raltegravir (RAL), and elvitegravir (EVG) remains relatively unknown. We tested a large collection of HIV-1 group O strains for their susceptibility to four classes of antiretroviral drugs namely nucleoside RT, non-nucleoside RT, integrase, and entry inhibitors knowing in advance the intrinsic resistance to NNRTIs. Drug target regions were sequenced to determine various polymorphisms and were phylogenetically analyzed. Replication kinetics and fitness assays were performed in U87-CD4(+)CCR5 and CXCR4 cells and peripheral blood mononuclear cells. With all antiretroviral drugs, group O HIV-1 showed higher variability in IC50 values than group M HIV-1. The mean IC50 values for entry and nucleoside reverse transcriptase inhibitor (NRTI) were similar for group O and M HIV-1 isolates. Despite similar susceptibility to maraviroc, the various phenotypic algorithms failed to predict CXCR4 usage based on the V3 Env sequences of group O HIV-1 isolates. Decreased sensitivity of group O HIV-1 to integrase or NNRTIs had no relation to replicative fitness. Group O HIV-1 isolates were 10-fold less sensitive to EVG inhibition than group M HIV-1. These findings suggest that in regions where HIV-1 group O is endemic, first line treatment regimens combining two NRTIs with RAL may provide more sustained virologic responses than the standard regimens involving an NNRTI or protease inhibitors. PMID- 26861575 TI - Nox/Duox Family of NADPH Oxidases: Lessons from Knockout Mouse Models. AB - Nox/Duox NADPH oxidases are now considered the primary, regulated sources of reactive oxygen species (ROS). These enzymes are expressed in diverse cells and tissues, and their products are essential in several physiological settings. Knockout mouse models are instrumental in identifying the physiological functions of Nox/Duox enzymes as well as in exploring the impact of their pharmacological targeting on disease progression. The currently available data from experiments on knockout animals suggest that the lack of non-phagocytic Nox/Duox enzymes often modifies the course and phenotype in many disease models. Nevertheless, as illustrated by studies on Nox4-deficient animals, the absence of Nox-derived ROS can also lead to aggravated disease manifestation, reinforcing the need for a more balanced view on the role of ROS in health and disease. PMID- 26861574 TI - Self-Management Strategies in Emerging Adults With Type 1 Diabetes. AB - INTRODUCTION: We examined changes in self-management behaviors after high school graduation in a cohort of emerging adults with type 1 diabetes. METHODS: Sixty four emerging adults reported on diabetes self-management behaviors at three time points over a 1-year period. Glycemic control and blood glucose monitoring frequency data were collected from the medical chart. RESULTS: Collaboration with parents decreased, diabetes problem-solving and communication increased, and glycemic control worsened during the first year after high school (p < .05). Problem solving appeared to be protective against worsening glycemic control; higher baseline diabetes problem solving significantly predicted better glycemic control at the 1-year follow-up. DISCUSSION: Emerging adults demonstrate increased independence in diabetes problem solving and communication with health care providers in the year after high school. Problem-solving skills may help emerging adults adapt type 1 diabetes self-care in response to unpredictable schedules after high-school, and promoting these skills may prevent deteriorations in glycemic control during this risky period. PMID- 26861576 TI - The relationship between environmental relative moldiness index values and asthma. AB - Indoor mold exposures have been qualitatively linked to asthma for more than 25 years. Our goal has been to turn this qualitative link into a quantitative assessment of asthma risk from mold exposures as estimated by the home's environmental relative moldiness index (ERMI) value. The home's ERMI value is derived from the quantitative PCR analysis of 36 molds in a dust sample. Six epidemiological studies of the relationship between ERMI values and asthma, in cities across the U.S., showed that both children and adults with asthma were living in homes with significantly higher ERMI values than the control or comparison homes. Based on these six studies, the accuracy of the ERMI value's link to occupant asthma was analyzed using receiver operating characteristic (ROC) curve and area under the curve (AUC) statistical analysis. The AUC was 0.69 which places the test accuracy in the "fair to good" range for a medical diagnostic test. A logistic regression analysis of the six studies was performed to generate an equation that can be used to predict occupant asthma at specific ERMI values. The ERMI metric may be a useful tool to link the quantification of mold contamination in U.S. homes to some asthma health effects. PMID- 26861578 TI - Nondestructive Total Excitation-Emission Fluorescence Microscopy Combined with Multi-Way Chemometric Analysis for Visually Indistinguishable Single Fiber Discrimination. AB - The potential of total excitation-emission fluorescence microscopy combined with multiway chemometric analysis was investigated for the nondestructive forensic analysis of textile fibers. The four pairs of visually indistinguishable fibers consisted of nylon 361 dyed with acid yellow 17 and acid yellow 23, acetate satin 105B dyed with disperse blue 3 and disperse blue 14, polyester 777 dyed with disperse red 1 and disperse red 19, and acrylic 864 dyed with basic green 1 and basic green 4. Excitation emission matrices were recorded with the aid of an inverted microscope and a commercial spectrofluorimeter. The full information content of excitation-emission matrices was processed with the aid of unsupervised parallel factor analysis (PARAFAC), PARAFAC supervised by linear discriminant analysis (LDA), and discriminant unfolded partial least-squares (DU PLS). The ability of the latter algorithm to classify the four pairs of fibers demonstrates the advantage of using the multidimensionality of fluorescence data formats for the nondestructive analysis of forensic fiber evidence. PMID- 26861580 TI - Analysis of an In-Service Examination for Core Pediatric Craniofacial Surgery Knowledge. AB - OBJECTIVE: Little is known about designing an effective residency curriculum for pediatric craniofacial surgery. This study elucidates the pediatric craniofacial curriculum of the Plastic Surgery In-Service Training Examination (PSITE) to facilitate knowledge acquisition during residency. DESIGN: Approximately, 6 consecutive PSITEs were reviewed for pediatric craniofacial questions (2010 2015). Subjects were categorized according to topics on the American Board of Plastic Surgery written board examination. Questions were categorized using an educational taxonomy model. Answer references were categorized by source and publication lag. RESULTS: Of 1174 PSITE questions, 147 tested pediatric craniofacial topics (12.5%). Questions appeared predominately in the Craniomaxillofacial section (83.0%, p < 0.001). The annual representation was stable more than 6 years (range: 10.2%-14.4%, p = 0.842). Question taxonomy favored interpretation (45.6%) and decision-making (40.8%) over recall (13.6%, p < 0.001) skills, and 41 questions had an associated image (27.9%) and most were photographic (76.7%, p < 0.001). The most frequently tested categories on the American Board of Plastic Surgery written examination content outline were craniofacial anomalies (23.5%), benign and malignant tumors (17.6%), and cleft lip and palate (12.5%). Overall, 80 unique journals were cited 304 times with a mean publication lag of 9.4 +/- 10.9 years. Plastic and Reconstructive Surgery (34.5%) was the most cited journal (p < 0.001). CONCLUSIONS: These data may assist in designating core knowledge competency in pediatric craniofacial surgery for plastic surgery residents. A further understanding of PSITE utility for core knowledge competency in pediatric craniofacial surgery would be the focus of future work. PMID- 26861581 TI - Intensive Simulation Training in Lower Limb Arterial Duplex Scanning Leads to Skills Transfer in Real-World Scenario. AB - OBJECTIVES: To train novices to perform an abbreviated duplex lower limb ultrasound scan using simulation training and assess real-world skills transference. METHODS: Novices undertook 3 days of simulation training. Their progress was assessed using the Duplex Ultrasound Objective Structured Assessment of Technical Skills (DUOSATS) for simulation and Cumulative Imaging Score (CIS). A final assessment day was held to assess DUOSATS for simulation and real patient scanning, CIS, cumulative diagnostic accuracy, and sections A and B of the Society of Vascular Technology examination. MSc students in vascular ultrasound were also assessed for comparison. RESULTS: A total of 17 novices and 7 MSc students with 3-month training participated. Novices improved DUOSATS for simulation scores between days 1, 3, and 4: 18 (17-19) vs 27 (25-28) vs 30 (28 32), (median [interquartile range], p < 0.001). Novices improved in CIS between days 1 and 3: 10 (10-13) vs 21 (19-21), p < 0.001, with a decline on day 4: 15.3 (11.3-18.3), p < 0.001. On the final assessment day, there were no significant differences between novices and MSc students in: DUOSATS for simulation scores (30 [28-32] vs 31 [6-31.5], p = 0.85); DUOSATS for patient assessment (31 [28.7 33.7] vs 26.7 [24.5-35.7], p = 0.41); CIS (15.3 [11.3-18.7] vs 20.7 [12.3-22.2], p = 0.2), respectively. However, novices performed better in section B of the Society of Vascular Technology examination compared with MSc students (72.9% vs 54.3%, p < 0.001). Novices also demonstrated a higher diagnostic accuracy when compared with MSc students (65.7% of arterial segments correctly assessed vs 47.6%, respectively [p = 0.044]). CONCLUSIONS: Intensive simulation of 3-day training achieved real patient-based assessments that were comparable to MSc students who were 3 months into their traditional training program. PMID- 26861579 TI - 0 + 5 Vascular Surgery Residents' Operative Experience in General Surgery: An Analysis of Operative Logs from 12 Integrated Programs. AB - OBJECTIVE: Integrated (0 + 5) vascular surgery (VS) residency programs must include 24 months of training in core general surgery. The Accreditation Council for Graduate Medical Education currently does not require specific case numbers in general surgery for 0 + 5 trainees; however, program directors have structured this time to optimize operative experience. The aim of this study is to determine the case volume and type of cases that VS residents are exposed to during their core surgery training. DESIGN: Accreditation council for graduate medical education operative logs for current 0 + 5 VS residents were obtained and retrospectively reviewed to determine general surgery case volume and distribution between open and laparoscopic cases performed. Standard statistical methods were applied. SETTING: A total of 12 integrated VS residency programs provided operative case logs for current residents. PARTICIPANTS: A total of 41 integrated VS residents in clinical years 2 through 5. RESULTS: During the postgraduate year-1 training year, residents participated in significantly more open than laparoscopic general surgery cases (p < 0.0001). This difference was consistent over the first 3 years of training. The most frequently logged open general surgery cases are hernia repair (20%), skin and soft tissue (7.4%), and breast (6.3%). Residents in programs with core surgery over 3 years participated in significantly more general surgery operations compared with residents in programs with core surgery spread out over 4 years (p = 0.035). CONCLUSIONS: 0 + 5 VS residents perform significantly more open operations than laparoscopic operations during their core surgery training. The majority of these operations are minor, nonabdominal procedures. The 0 + 5 VS residency program general surgery operative training requirements should be reevaluated and case minimums defined. The general surgery training component of 0 + 5 VS residencies may need to be restructured to meet the needs of current and future trainees. PMID- 26861582 TI - 3D Printout Models vs. 3D-Rendered Images: Which Is Better for Preoperative Planning? AB - INTRODUCTION: Correct interpretation of a patient's anatomy and changes that occurs secondary to a disease process are crucial in the preoperative process to ensure optimal surgical treatment. In this study, we presented 3 different pancreatic cancer cases to surgical residents in the form of 3D-rendered images and 3D-printed models to investigate which modality resulted in the most appropriate preoperative plan. METHODS: We selected 3 cases that would require significantly different preoperative plans based on key features identifiable in the preoperative computed tomography imaging. 3D volume rendering and 3D printing were performed respectively to create 2 different training ways. A total of 30, year 1 surgical residents were randomly divided into 2 groups. Besides traditional 2D computed tomography images, residents in group A (n = 15) reviewed 3D computer models, whereas in group B, residents (n = 15) reviewed 3D-printed models. Both groups subsequently completed an examination, designed in-house, to assess the appropriateness of their preoperative plan and provide a numerical score of the quality of the surgical plan. RESULTS: Residents in group B showed significantly higher quality of the surgical plan scores compared with residents in group A (76.4 +/- 10.5 vs. 66.5 +/- 11.2, p = 0.018). This difference was due in large part to a significant difference in knowledge of key surgical steps (22.1 +/- 2.9 vs. 17.4 +/- 4.2, p = 0.004) between each group. All participants reported a high level of satisfaction with the exercise. CONCLUSION: Results from this study support our hypothesis that 3D-printed models improve the quality of surgical trainee's preoperative plans. PMID- 26861583 TI - Dental Student Hand Hygiene Decreased With Increased Clinical Experience. AB - OBJECTIVE: To investigate the effectiveness, related knowledge, attitudes, and practices of hand hygiene (HH) among dental students with different levels of clinical experience. DESIGN: This was a cross-sectional analytical study. Bacterial samples on the participants' hands were obtained using a swab technique before and after handwashing, for oral surgical procedures. After culturing, the colony-forming units were counted. Self-reported questionnaires reflecting the knowledge, attitudes, and practices related to HH were completed by the participants. SETTING: This study was performed in a primary oral health care institution, Faculty of Dentistry, Chulalongkorn University (Bangkok, Thailand). Bacterial samples and self-reported questionnaires were collected in the Department of Oral and Maxillofacial Surgery. Bacterial culture was performed in the Department of Microbiology. PARTICIPANTS: The 120 participants comprised first, second, third-year clinical training students (CTs), and postgraduate dental students (PGs) (32, 34, 30, and 24 participants, respectively). RESULTS: More than 99% of the bacteria were eliminated from the participants' hands after handwashing. Significantly higher numbers of bacteria were recovered from the hands of the PGs compared with those of the CTs, and the hands of the third-year CTs compared with those of the first-year CTs (p < 0.001), after HH. The first year CTs had the highest attitude scores, whereas the PGs had the lowest practice scores. The knowledge scores were similar in all groups. CONCLUSION: HH effectiveness, attitudes, and practices of dental students decreased as students gained more clinical experience, whereas knowledge did not. Our results suggest that HH instruction should be given throughout the duration of dental students' education. PMID- 26861584 TI - The Effect of Applicant Publication Volume on the Orthopaedic Residency Match. AB - BACKGROUND: Research is an important factor used in evaluating applicants to orthopaedic training programs. Current reports regarding the publication rate among prospective residents are likely inaccurate. It is unknown whether research productivity is weighted more heavily at programs affiliated with research-driven institutions. OBJECTIVE: To establish accurate baseline data on publication rate among matched applicants to orthopaedic residency programs and to compare publication rates between applicants who matched at research-focused institutions and those who matched elsewhere. DESIGN: We performed a literature search for each U.S. resident in the 2013-2014 intern class. Number of publications: (1) in total, (2) in orthopaedic journals, and (3) as first/last author were recorded. Publication rate at the top 25 programs (according to medical school and departmental National Institutes of Health [NIH] funding and U.S. News ranking) was compared statistically against all others. RESULTS: Average number of publications per intern for all programs was 1.28 +/- 0.15. Number of total and first/last author publications was significantly greater for programs affiliated with medical schools and departments in the top 25 for NIH funding, and at schools in the top 25 U.S. News rankings. Publication rate in orthopaedic journals was significantly higher for programs affiliated with departments in the top 25 for NIH funding and at top 25 U.S. News medical schools. CONCLUSIONS: The average matched applicant to an orthopaedic residency program publishes in the peer-reviewed literature less frequently than previously reported. Matched applicants at research-focused institutions tended to have more publications than those who matched at other programs. PMID- 26861585 TI - L1CAM is an independent predictor of poor survival in endometrial cancer - An analysis of The Cancer Genome Atlas (TCGA). AB - BACKGROUND: L1-cell adhesion molecule (L1CAM) was previously reported to carry a poor prognosis in Stage I, low-risk endometrial cancer (EC). We evaluated the role of L1CAM among all stages and histologies in ECs in The Cancer Genome Atlas (TCGA). METHODS: Clinical information and RNA-Seq expression data were derived from TCGA uterine cancer cohort. Associations between L1CAM expression and clinical factors were tested with linear and logistic regression. Differences in survival between "high" and "low" expression groups (defined by median expression) of L1CAM were compared using Cox regression analysis, with p-values calculated via log-rank test. Kaplan-Meier curves were tested with the log-rank test. RESULTS: Patient characteristics of 545 primary tumors with RNA-Seq gene expression data were analyzed. Median age was 64years (range 31-90). Stage I, II, III, and IV comprised 62%, 10%, 23%, and 5%, respectively. 75% were endometrioid; 21% serous. Grade 1, 2, and 3 comprised 18%, 22%, and 60%, respectively. Median follow-up was 23.0months. High L1CAM expression was associated with advanced stage (OR 3.2), high grade (OR=6.8), serous histology (OR=16.3), positive cytology (OR=3.5), positive pelvic (OR=21.8) and para-aortic lymph nodes (OR=10.3) (all p<=0.001). High L1CAM was associated with a median overall survival (OS) of 107months, versus not reached for low L1-expressing ECs (HR=3.46, CI 1.97-6.07, p<0.001). On multivariate analysis, L1CAM expression remained an independent prognostic variable in predicting OS in EC. CONCLUSIONS: L1CAM expression is an independent predictor of poor survival in endometrial cancer, and is associated with advanced stage, high-risk endometrial cancer. PMID- 26861586 TI - Inhibitory activities against rice pathogens of 8-hydroxy-2,4,6-octatriynamide from Agrocybe sp. AB - 8-Hydroxy-2,4,6-octatriynamide, a natural polyacetylene with inhibitory activities against rice pathogens, was isolated from the liquid fermentation broth of strain Agrocybe sp. YB2005 during screening for new natural chemical agents to control rice pathogens. 8-hydroxy-2,4,6-octatriynamide was purified by consecutive chromatography over a Cl8 reversed phase silica gel, sephadex LH-20 and silica gel. The chemical structure of 8-hydroxy-2,4,6-octatriynamide was elucidated through spectroscopic analyses, including 1D- and 2D-NMR, ESI mass spectrometry and X-ray single crystal diffraction. Bioassays showed that 8 hydroxy-2,4,6-octatriynamide could significantly inhibit growth of Xanthomonas oryzae with an MIC of 53.1 MUM in a 96-well plate and the growth of Rhizoctonia solani at 1.02 mM in a 24-well plate. When rice leaves were inoculated with Magnaporthe grisea and cultured in artificial nutrition liquid containing 0.34 mM 8-hydroxy-2,4,6-octatriynamide, no rice blast was observed. The present study implied that 8-hydroxy-2,4,6-octatriynamide could be a candidate agent against rice pathogens. PMID- 26861588 TI - Upper Critical Field and Kondo Effects in Fe(Te0.9Se0.1) Thin Films by Pulsed Field Measurements. AB - The transition temperatures of epitaxial films of Fe(Te0:9Se0:1) are remarkably insensitive to applied magnetic field, leading to predictions of upper critical fields Bc2(T = 0) in excess of 100 T. Using pulsed magnetic fields, we find Bc2(0) to be on the order of 45 T, similar to values in bulk material and still in excess of the paramagnetic limit. The same films show strong magnetoresistance in fields above Bc2(T), consistent with the observed Kondo minimum seen above Tc. Fits to the temperature dependence in the context of the WHH model, using the experimental value of the Maki parameter, require an effective spin-orbit relaxation parameter of order unity. We suggest that Kondo localization plays a similar role to spin-orbit pair breaking in making WHH fits to the data. PMID- 26861589 TI - Atrophying tinea versicolor with epidermal atrophy. PMID- 26861587 TI - Variation in susceptibility of African Plasmodium falciparum malaria parasites to TEP1 mediated killing in Anopheles gambiae mosquitoes. AB - Anopheles gambiae s.s. mosquitoes are efficient vectors for Plasmodium falciparum, although variation exists in their susceptibility to infection. This variation depends partly on the thioester-containing protein 1 (TEP1) and TEP depletion results in significantly elevated numbers of oocysts in susceptible and resistant mosquitoes. Polymorphism in the Plasmodium gene coding for the surface protein Pfs47 modulates resistance of some parasite laboratory strains to TEP1 mediated killing. Here, we examined resistance of P. falciparum isolates of African origin (NF54, NF165 and NF166) to TEP1-mediated killing in a susceptible Ngousso and a refractory L3-5 strain of A. gambiae. All parasite clones successfully developed in susceptible mosquitoes with limited evidence for an impact of TEP1 on transmission efficiency. In contrast, NF166 and NF165 oocyst densities were strongly reduced in refractory mosquitoes and TEP1 silencing significantly increased oocyst densities. Our results reveal differences between African P. falciparum strains in their capacity to evade TEP1-mediated killing in resistant mosquitoes. There was no significant correlation between Pfs47 genotype and resistance of a given P. falciparum isolate for TEP1 killing. These data suggest that polymorphisms in this locus are not the sole mediators of immune evasion of African malaria parasites. PMID- 26861591 TI - The agar diffusion scratch assay--A novel method to assess the bioactive and cytotoxic potential of new materials and compounds. AB - A profound in vitro evaluation not only of the cytotoxic but also of bioactive potential of a given compound or material is crucial for predicting potential effects in the in vivo situation. However, most of the current methods have weaknesses in either the quantitative or qualitative assessment of cytotoxicity and/or bioactivity of the test compound. Here we describe a novel assay combining the ISO 10993-5 agar diffusion test and the scratch also termed wound healing assay. In contrast to these original tests this assay is able to detect and distinguish between cytotoxic, cell migration modifying and cytotoxic plus cell migration modifying compounds, and this at higher sensitivity and in a quantitative way. PMID- 26861590 TI - Dynamic Myofibrillar Remodeling in Live Cardiomyocytes under Static Stretch. AB - An increase in mechanical load in the heart causes cardiac hypertrophy, either physiologically (heart development, exercise and pregnancy) or pathologically (high blood pressure and heart-valve regurgitation). Understanding cardiac hypertrophy is critical to comprehending the mechanisms of heart development and treatment of heart disease. However, the major molecular event that occurs during physiological or pathological hypertrophy is the dynamic process of sarcomeric addition, and it has not been observed. In this study, a custom-built second harmonic generation (SHG) confocal microscope was used to study dynamic sarcomeric addition in single neonatal CMs in a 3D culture system under acute, uniaxial, static, sustained stretch. Here we report, for the first time, live cell observations of various modes of dynamic sarcomeric addition (and how these real-time images compare to static images from hypertrophic hearts reported in the literature): 1) Insertion in the mid-region or addition at the end of a myofibril; 2) Sequential addition with an existing myofibril as a template; and 3) Longitudinal splitting of an existing myofibril. The 3D cell culture system developed on a deformable substrate affixed to a stretcher and the SHG live-cell imaging technique are unique tools for real-time analysis of cultured models of hypertrophy. PMID- 26861592 TI - Picosecond metrology of laser-driven proton bursts. AB - Tracking primary radiation-induced processes in matter requires ultrafast sources and high precision timing. While compact laser-driven ion accelerators are seeding the development of novel high instantaneous flux applications, combining the ultrashort ion and laser pulse durations with their inherent synchronicity to trace the real-time evolution of initial damage events has yet to be realized. Here we report on the absolute measurement of proton bursts as short as 3.5+/-0.7 ps from laser solid target interactions for this purpose. Our results verify that laser-driven ion acceleration can deliver interaction times over a factor of hundred shorter than those of state-of-the-art accelerators optimized for high instantaneous flux. Furthermore, these observations draw ion interaction physics into the field of ultrafast science, opening the opportunity for quantitative comparison with both numerical modelling and the adjacent fields of ultrafast electron and photon interactions in matter. PMID- 26861593 TI - Melatonin Prevents Mitochondrial Damage Induced by Doxorubicin in Mouse Fibroblasts Through Ampk-Ppar Gamma-Dependent Mechanisms. AB - BACKGROUND Doxorubicin (brand name: Adriamycin(r)) is used to treat solid tissue cancer but it also affects noncancerous tissues. Its mechanism of cytotoxicity is probably related to increased oxidation, mitochondrial dysfunction, and apoptosis. Melatonin is reported to have antiapoptotic and antioxidative effects. The aim of this study was to determine whether melatonin would counteract in vitro cytotoxicity of doxorubicin in mouse fibroblasts and determine the pathway of its action against doxorubicin-induced apoptosis. MATERIAL AND METHODS We measured markers of apoptosis (cytochrome-c, mitochondrial membrane potential, and apoptotic cell number) and oxidative stress (total oxidant and antioxidant status) and calculated oxidant stress index in 4 groups of fibroblasts: controls, melatonin-treated, doxorubicin-treated, and fibroblasts concomittantly treated with a combination of melatonin and doxorubicin. RESULTS Melatonin given with doxorubicin succesfully countered apoptosis generated by doxorubicin alone, which points to its potential as a protective agent against cell death in doxorubicin chemotherapy. This also implies that patients should be receiving doxorubicin treatment when their physiological level of melatonin is at its highest, which is early in the morning. CONCLUSIONS This physiological level may not be high enough to overcome doxorubicin-induced oxidative stress, but adjuvant melatonin treatment may improve quality of life. Further research is needed to verify our findings. PMID- 26861595 TI - Anisotropic structural and optical properties of semi-polar (11-22) GaN grown on m-plane sapphire using double AlN buffer layers. AB - We report the anisotropic structural and optical properties of semi-polar (11-22) GaN grown on m-plane sapphire using a three-step growth method which consisted of a low temperature AlN buffer layer, followed by a high temperature AlN buffer layer and GaN growth. By introducing double AlN buffer layers, we substantially improve the crystal and optical qualities of semi-polar (11-22) GaN, and significantly reduce the density of stacking faults and dislocations. The high resolution x-ray diffraction measurement revealed that the in-plane anisotropic structural characteristics of GaN layer are azimuthal dependent. Transmission electron microscopy analysis showed that the majority of dislocations in the GaN epitaxial layer grown on m-sapphire are the mixed-type and the orientation of GaN layer was rotated 58.4 degrees against the substrate. The room temperature photoluminescence (PL) spectra showed the PL intensity and wavelength have polarization dependence along parallel and perpendicular to the [1-100] axis (polarization degrees ~ 0.63). The realization of a high polarization semi-polar GaN would be useful to achieve III-nitride based lighting emission device for displays and backlighting. PMID- 26861597 TI - The impact of postmastectomy and regional nodal radiation after neoadjuvant chemotherapy for clinically lymph node-positive breast cancer: a National Cancer Database (NCDB) analysis. AB - BACKGROUND: Following neoadjuvant chemotherapy (NAC), the optimal strategies for postmastectomy radiotherapy (PMRT) and regional nodal irradiation (RNI) after breast-conserving surgery (BCS) are controversial. In this analysis, we evaluate the impact of these radiotherapy (RT) approaches for women with clinically node positive breast cancer treated with NAC in the National Cancer Database (NCDB). PATIENTS AND METHODS: Women with cT1-3 cN1 M0 breast cancer treated with NAC were divided into four cohorts by surgery [Mastectomy (Mast) versus BCS] and post chemotherapy pathologic nodal status (ypN0 versus ypN+). Overall survival (OS) was estimated using the Kaplan-Meier method and RT approaches were analyzed using the log-rank test, multivariate Cox models, and propensity score-matched analyses. RESULTS: From 2003 to 2011, 15 315 cases were identified including 3040 Mast-ypN0, 7243 Mast-ypN+, 2070 BCS-ypN0, and 2962 BCS-ypN+ patients. On univariate analysis, PMRT was associated with improved OS for both Mast-ypN0 (P = 0.019) and Mast-ypN+ (P < 0.001) patients. On multivariate analyses adjusted for factors including age, comorbidity score, cT stage, in-breast pathologic complete response, axillary surgery, ypN stage, estrogen receptor status and hormone therapy, PMRT remained independently associated with improved OS among Mast-ypN0 [hazard ratio (HR) = 0.729, 95% confidence interval (CI) 0.566-0.939, P = 0.015] and Mast-ypN+ patients (HR = 0.772, 95% CI 0.689-0.866, P < 0.001). No differences in OS were observed with the addition of RNI to breast RT for BCS ypN0 or BCS-ypN+ patients. Propensity score-matched analyses demonstrated identical patterns of significance. On subset analysis, OS was improved with PMRT in each pathologic nodal subgroup (ypN0, ypN1, and ypN2-3) (all P < 0.05). CONCLUSIONS: In the largest reported analysis of RT for cN1 patients treated with NAC, PMRT was associated with improved OS for all pathologic nodal subgroups. No OS differences were observed with the addition of RNI to breast RT. PMID- 26861594 TI - Transcriptome adaptation of the bovine mammary gland to diets rich in unsaturated fatty acids shows greater impact of linseed oil over safflower oil on gene expression and metabolic pathways. AB - BACKGROUND: Nutritional strategies can decrease saturated fatty acids (SFAs) and increase health beneficial fatty acids (FAs) in bovine milk. The pathways/genes involved in these processes are not properly defined. Next-generation RNA sequencing was used to investigate the bovine mammary gland transcriptome following supplemental feeding with 5% linseed oil (LSO) or 5% safflower oil (SFO). Holstein cows in mid-lactation were fed a control diet for 28 days (control period) followed by supplementation with 5% LSO (12 cows) or 5% SFO (12 cows) for 28 days (treatment period). Milk and mammary gland biopsies were sampled on days-14 (control period), +7 and +28 (treatment period). Milk was used to measure fat(FP)/protein(PP) percentages and individual FAs while RNA was subjected to sequencing. RESULTS: Milk FP was decreased by 30.38% (LSO) or 32.42% (SFO) while PP was unaffected (LSO) or increased (SFO). Several beneficial FAs were increased by LSO (C18:1n11t, CLA:10t12c, CLA:9c11t, C20:3n3, C20:5n3, C22:5n3) and SFO (C18:1n11t, CLA:10t12c, C20:1c11, C20:2, C20:3n3) while several SFAs (C4:0, C6:0, C8:0, C14:0, C16:0, C17:0, C24:0) were decreased by both treatments (P < 0.05). 1006 (460 up- and 546 down-regulated) and 199 (127 up- and 72 down-regulated) genes were significantly differentially regulated (DE) by LSO and SFO, respectively. Top regulated genes (>= 2 fold change) by both treatments (FBP2, UCP2, TIEG2, ANGPTL4, ALDH1L2) are potential candidate genes for milk fat traits. Involvement of SCP2, PDK4, NQO1, F2RL1, DBI, CPT1A, CNTFR, CALB1, ACADVL, SPTLC3, PIK3CG, PIGZ, ADORA2B, TRIB3, HPGD, IGFBP2 and TXN in FA/lipid metabolism in dairy cows is being reported for the first time. Functional analysis indicated similar and different top enriched functions for DE genes. DE genes were predicted to significantly decrease synthesis of FA/lipid by both treatments and FA metabolism by LSO. Top canonical pathways associated with DE genes of both treatments might be involved in lipid/cholesterol metabolism. CONCLUSION: This study shows that rich alpha-linolenic acid LSO has a greater impact on mammary gland transcriptome by affecting more genes, pathways and processes as compared to SFO, rich in linoleic acid. Our study suggest that decrease in milk SFAs was due to down-regulation of genes in the FA/lipid synthesis and lipid metabolism pathways while increase in PUFAs was due to increased availability of ruminal biohydrogenation metabolites that were up taken and incorporated into milk or used as substrate for the synthesis of PUFAs. PMID- 26861596 TI - Feasibility and safety of low-flow extracorporeal carbon dioxide removal to facilitate ultra-protective ventilation in patients with moderate acute respiratory distress sindrome. AB - BACKGROUND: Mechanical ventilation with a tidal volume (VT) of 6 mL/kg/predicted body weight (PBW), to maintain plateau pressure (Pplat) lower than 30 cmH2O, does not completely avoid the risk of ventilator induced lung injury (VILI). The aim of this study was to evaluate safety and feasibility of a ventilation strategy consisting of very low VT combined with extracorporeal carbon dioxide removal (ECCO2R). METHODS: In fifteen patients with moderate ARDS, VT was reduced from baseline to 4 mL/kg PBW while PEEP was increased to target a plateau pressure- (Pplat) between 23 and 25 cmH2O. Low-flow ECCO2R was initiated when respiratory acidosis developed (pH < 7.25, PaCO2 > 60 mmHg). Ventilation parameters (VT, respiratory rate, PEEP), respiratory compliance (CRS), driving pressure (DeltaP = VT/CRS), arterial blood gases, and ECCO2R system operational characteristics were collected during the period of ultra-protective ventilation. Patients were weaned from ECCO2R when PaO2/FiO2 was higher than 200 and could tolerate conventional ventilation settings. Complications, mortality at day 28, need for prone positioning and extracorporeal membrane oxygenation, and data on weaning from both MV and ECCO2R were also collected. RESULTS: During the 2 h run in phase, VT reduction from baseline (6.2 mL/kg PBW) to approximately 4 mL/kg PBW caused respiratory acidosis (pH < 7.25) in all fifteen patients. At steady state, ECCO2R with an average blood flow of 435 mL/min and sweep gas flow of 10 L/min was effective at correcting pH and PaCO2 to within 10 % of baseline values. PEEP values tended to increase at VT of 4 mL/kg from 12.2 to 14.5 cmH2O, but this change was not statistically significant. Driving pressure was significantly reduced during the first two days compared to baseline (from 13.9 to 11.6 cmH2O; p < 0.05) and there were no significant differences in the values of respiratory system compliance. Rescue therapies for life threatening hypoxemia such as prone position and ECMO were necessary in four and two patients, respectively. Only two study-related adverse events were observed (intravascular hemolysis and femoral catheter kinking). CONCLUSIONS: The low-flow ECCO2R system safely facilitates a low volume, low pressure ultra-protective mechanical ventilation strategy in patients with moderate ARDS. PMID- 26861598 TI - Cancer-associated toll-like receptor modulation and insinuation in infection susceptibility: association or coincidence? AB - Toll-like receptors (TLRs) are key players in maintaining protection against any invading pathogen. These molecules are microbial sensing proteins which detect pathogen-associated molecular patterns and induce the body's innate immune system to elicit a response against invading pathogens. In addition to their role in pathogen recognition and elimination, these proteins are highly important in cancer biology and also play a variety of roles in normal to cancerous transformation or its prevention. There is much published literature on the role of TLRs in pathogen recognition and elimination, but recently the number of articles relevant to the role of TLR in carcinogenesis has increased due to their importance in this area. On the one hand, they are involved in microbial elimination and, on the other hand, their modulation during cancer development has several implications. Accumulating a diverse thread of cancer-associated TLR modulation and infection susceptibility has several caveats. Some cancer associated TLR modulation increases susceptibility to particular infections, while increased expression of certain TLR was found to help in the carcinogenic process through inducing inflammation. This article concludes that clinicians should consider TLR modulation during infection risk assessment in cancer patients. These modulations should also be considered while designing management strategies against cancer and its associated infections. PMID- 26861599 TI - Reply to the letter to the editor 'Number-Needed-To-Treat for pricing costly anti cancer drugs. The example of Regorafenib in metastatic colorectal cancer' by Graziano et al. PMID- 26861600 TI - The use of ipilimumab in patients with rheumatoid arthritis and metastatic melanoma. PMID- 26861601 TI - Dendritic cells stimulated by MUC1 antigen could induce lymphocytes' anergy through PD-L2 but not through PD-L1 patway. PMID- 26861602 TI - Statistical controversies in clinical research: statistical significance-too much of a good thing .... AB - The use and interpretation of P values is a matter of debate in applied research. We argue that P values are useful as a pragmatic guide to interpret the results of a clinical trial, not as a strict binary boundary that separates real treatment effects from lack thereof. We illustrate our point using the result of BOLERO-1, a randomized, double-blind trial evaluating the efficacy and safety of adding everolimus to trastuzumab and paclitaxel as first-line therapy for HER2+ advanced breast cancer. In this trial, the benefit of everolimus was seen only in the predefined subset of patients with hormone receptor-negative breast cancer at baseline (progression-free survival hazard ratio = 0.66, P = 0.0049). A strict interpretation of this finding, based on complex 'alpha splitting' rules to assess statistical significance, led to the conclusion that the benefit of everolimus was not statistically significant either overall or in the subset. We contend that this interpretation does not do justice to the data, and we argue that the benefit of everolimus in hormone receptor-negative breast cancer is both statistically compelling and clinically relevant. PMID- 26861603 TI - Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial. AB - BACKGROUND: Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. PATIENTS AND METHODS: This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed >=4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] >=1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. RESULTS: Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. CONCLUSION: These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. CLINICAL TRIALS NUMBER: Australian New Zealand Clinical Trials Registry (www.anzctr.org.au), ACTRN12607000137493. PMID- 26861604 TI - FOLFOXIRI or FOLFOXIRI plus bevacizumab as first-line treatment of metastatic colorectal cancer: a propensity score-adjusted analysis from two randomized clinical trials. AB - BACKGROUND: FOLFOXIRI plus bevacizumab is a valid option as upfront treatment for metastatic colorectal cancer (mCRC) patients. While several trials investigated the effect of combining bevacizumab with different chemotherapy regimens, including fluoropyrimidines monotherapy and oxaliplatin- or irinotecan-containing doublets, no randomized comparison assessing the impact of the addition of bevacizumab to FOLFOXIRI is available. PATIENTS AND METHODS: A total of 122 mCRC patients received first-line FOLFOXIRI in the phase III trial by the GONO (FOLFOXIRI group) and 252 patients received first-line FOLFOXIRI plus bevacizumab in the TRIBE trial (FOLFOXIRI plus bevacizumab group). A propensity score adjusted method was adopted to provide an estimation of the benefit from the addition of bevacizumab to FOLFOXIRI in terms of survival and activity parameters. RESULTS: Patients in the FOLFOXIRI group had more frequently Eastern Cooperative Oncology Group performance status of one or two, high Kohne score, metachronous and liver-limited disease, had previously received adjuvant treatments and had their primary tumors resected. The median progression-free survival (PFS) was 12.3 months in the FOLFOXIRI plus bevacizumab group compared with 10.0 months in the FOLFOXIRI group {propensity score-adjusted hazard ratio (HR) 0.74 [95% confidence interval (CI) 0.59-0.94], P = 0.013}. This association was significant also in the multivariable model (P = 0.024). The median OS was 29.8 months in the FOLFOXIRI plus bevacizumab group compared with 23.6 months in the FOLFOXIRI group [propensity score-adjusted HR: 0.72 (95% CI 0.56-0.93), P = 0.014]. At the multivariable model, the addition of bevacizumab was still associated with significantly longer OS (P = 0.030). No significant differences in RECIST response rate (RR) [65.1% versus 55.7%; propensity score-adjusted odds ratio (OR): 1.29 (95% CI 0.81-2.05), P = 0.280], early RR [62.7% versus 57.8%; OR: 1.14 (95% CI 0.68-1.93), P = 0.619] and median depth of response (42.2% versus 53.8%, P = 0.259) were reported. CONCLUSIONS: Though in the absence of a randomized comparison, the addition of bevacizumab to FOLFOXIRI provides significant benefit in PFS and OS, thus supporting the use of FOLFOXIRI plus bevacizumab as upfront treatment for mCRC patients. TRIALS' NUMBERS: NCT01219920 and NCT00719797. PMID- 26861605 TI - Prognostic factors in patients with poor-risk germ-cell tumors: a retrospective analysis of the Indiana University experience from 1990 to 2014. AB - BACKGROUND: Based on the risk stratification from the International Germ Cell Cancer Collaborative Group (IGCCCG), only 14% of patients with metastatic germ cell tumors (GCT) had poor-risk disease with a 5-year progression-free survival (PFS) rate of 41% and a 5-year overall survival (OS) rate of only 48%. This analysis attempts to identify prognostic factors for patients with poor-risk disease. PATIENTS AND METHODS: We conducted a retrospective analysis of all patients with GCT diagnosed and treated at Indiana University from 1990 to 2014. Clinical and pathological characteristics were available for all patients and all of them were treated with cisplatin-etoposide-based chemotherapy. Cox proportional hazards models were used to target significant predictors of disease progression and mortality. A significance level of 5% was used in the analysis. RESULTS: We identified 273 consecutive patients with poor-risk GCT (PRGCT). Median follow-up time was 8 years (range 0.03-24.5). The 5-year PFS and OS rates were 58% [95% confidence interval (CI) 51% to 63%] and 73% (95% CI 67% to 78%), respectively. In multivariate survival analyses, multiple risk factors were associated with disease progression, including liver metastasis, brain metastasis, primary mediastinal nonseminomatous GCT (PMNSGCT), and elevation in logarithmic beta-hCG. Significant predictors of mortality were PMNSGCT [hazard ratio (HR) 4.63, 95% CI 2.25-9.56; P < 0.001], brain metastasis (HR 3.30, 95% CI 1.74-6.23; P < 0.001), and increasing age (HR 1.03, 95% CI 1.01-1.06; P = 0.02). CONCLUSIONS: Patients with PMNSGCT, brain metastasis, or with increasing age are at higher risk of death than their counterparts. This contemporary cohort (1990 2014) of 273 patients with PRGCT had improved PFS and OS outcomes than those from the historical IGCCCG group of patients (1975-1990). PMID- 26861606 TI - Molecular classification of gastric cancer. AB - Gastric cancer (GC), a heterogeneous disease characterized by epidemiologic and histopathologic differences across countries, is a leading cause of cancer related death. Treatment of GC patients is currently suboptimal due to patients being commonly treated in a uniform fashion irrespective of disease subtype. With the advent of next-generation sequencing and other genomic technologies, GCs are now being investigated in great detail at the molecular level. High-throughput technologies now allow a comprehensive study of genomic and epigenomic alterations associated with GC. Gene mutations, chromosomal aberrations, differential gene expression and epigenetic alterations are some of the genetic/epigenetic influences on GC pathogenesis. In addition, integrative analyses of molecular profiling data have led to the identification of key dysregulated pathways and importantly, the establishment of GC molecular classifiers. Recently, The Cancer Genome Atlas (TCGA) network proposed a four subtype classification scheme for GC based on the underlying tumor molecular biology of each subtype. This landmark study, together with other studies, has expanded our understanding on the characteristics of GC at the molecular level. Such knowledge may improve the medical management of GC in the future. PMID- 26861607 TI - Prognostic impact of extra-nodal extension on colon and rectal cancer should be investigated separately. PMID- 26861608 TI - A phase II study of everolimus (RAD001), an mTOR inhibitor plus CHOP for newly diagnosed peripheral T-cell lymphomas. AB - BACKGROUND: Everolimus, an oral mTOR inhibitor, has single-agent activity against relapsed lymphomas. Thus, we carried out a phase II study of everolimus in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) as a first-line treatment for patients with peripheral T-cell lymphoma (PTCL) based on our phase I study results. PATIENTS AND METHODS: Participants (n = 30) received CHOP with 5 mg everolimus per day from day 1 to 14 every 21 days for a total of six cycles. The primary end point was the overall response rate (ORR), which included complete response (CR) and partial response (PR) to this regimen. Immunohistochemistry was used to evaluate the expression of phosphatase and tensin homology (PTEN) and phosphorylated S6 kinase (pS6K) as a response. RESULTS: The objective response rate was 90% with CR (n = 17) and PR (n = 10). The CR rate was different among subtypes; angioimmunoblastic T-cell lymphoma (AITL, n = 3) had a CR whereas PTCL-not-otherwise specified and ALK negative anaplastic large-cell lymphoma (ALCL) patients showed 63% (12/19) and 29% (2/7) of CR rate, respectively. This difference in CR rate among subtypes was associated with PTEN loss because PTEN loss was not seen in AITL but 33% of ALCL patients. The most common toxicity was hematological, with 80% of patients experiencing at least one event of grade 3/4 neutropenia, and 60% of patients had grade 3/4 thrombocytopenia. CONCLUSION: The everolimus plus CHOP was effective for PTCL patients, and its efficacy might be related with the preservation of PTEN. PMID- 26861609 TI - DopAmide: Novel, Water-Soluble, Slow-Release l-dihydroxyphenylalanine (l-DOPA) Precursor Moderates l-DOPA Conversion to Dopamine and Generates a Sustained Level of Dopamine at Dopaminergic Neurons. AB - BACKGROUND: Long-term l-dihydroxyphenylalanine (l-DOPA) treatment of Parkinson's disease (PD) is associated with motor complications known as l-DOPA-induced dyskinesias (LID) and on/off fluctuations, which are linked to unsteady pulsatile dopaminergic stimulation. AIM: The objective of this study was to improve l-DOPA treatment by slowing and stabilizing dopamine (DA) production in the brain and increasing water solubility to provide a rescue therapy for PD. RESULTS: We synthesized l-DOPA-amide, a novel l-DOPA precursor called DopAmide. DopAmide is water soluble and, as a prodrug, requires hydrolysis prior to decarboxylation by the aromatic l-amino acid decarboxylase (EC 4.1.1.28; AAAD). In the 6-OH-dopamine (6-OHDA)-lesioned rats, DopAmide maintained steady rotations for up to 4 h compared with 2 h by l-DOPA, suggesting that this rate-limiting step generated a sustained level of DA at dopaminergic neurons. Pharmacokinetic studies showed elimination half-life of l-DOPA in the plasma after DopAmide treatment of t1/2 = 4.1 h, significantly longer than t1/2 = 2.9 h after treatment with l-DOPA, consistent with the 6-OHDA results. CONCLUSIONS: The slow conversion of DopAmide to l-DOPA provides a sustained level of DA in the dopaminergic cells, shown by the long 6-OHDA steady rotations. The water solubility and improved bioavailability may help reduce medication frequency associated with l-DOPA treatment of PD. Sustained levels of DA might lower the super-sensitization of DA signaling and potentially attenuate l-DOPA adverse effects. PMID- 26861610 TI - Regulators in the apoptotic pathway during spermatogenesis: Killers or guards? AB - Apoptosis occurs at any time in the ontogeny of the testis, especially during the first wave of spermatogenesis. However, the exact mechanisms by which homeostasis of apoptosis and survival in GCs and mature sperm are orchestrated remain unclear. Three pathways during the process of apoptosis in mammals are discussed extensively. The three pathways are extrinsic pathway, mitochondrial pathway and endoplasmic reticulum pathway. Based on that, many factors, such as growth factors (SCF, FGF, TGF), hormones (FSH, LH, E2, MIS), partial oxygen pressure, and testis specific genes are involved in apoptosis and survival process. The pathways of apoptosis adopted by the GCs and sperm depend on the types of stimuli they receive. Diverse pathways are initiated in heat-stress induced apoptosis of GCs and the destiny of GCs suppressed by hyperglycemia is mainly regulated by a rheostat of total oxidants and anti-oxidants which leading to intrinsic pathway. In this review, we provide an overview of three classic pathways and important factors involved in the process of germ cell apoptosis and survival, and discuss the recent advances made in understanding of the molecular mechanisms of spermatogenic cells and sperm response to stress-inducers, such as heat stress and hyperglycemia. All the findings may provide clues to the control of male fertility or treating germ cell tumors and other testis associated pathological conditions, at the same time, a novel idea may result in devising much safer contraception with high efficiency. PMID- 26861611 TI - A novel CHH gene from the Pacific white shrimp Litopenaeus vannamei was characterized and found highly expressed in gut and less in eyestalk and other extra-eyestalk tissues. AB - The crustacean hyperglycemic hormone (CHH) family is an important group of neuropeptides involved in controlling growth, reproduction, and stress response in decapod species. In this study, a new gene containing 4 exons-3 introns flanked by canonical 5'-GT-AG-3' intron splice-site junctions was isolated from Litopenaeus vannamei. Two full length transcripts of this CHH were isolated from eyestalk and pericardial tissue of males and females using rapid amplification of cDNA ends (RACE). Transcripts sequences were 1578bp in length in males pericardial tissues and in males and females eyestalk with 100% identity, but the transcript isolated from females pericardial tissues was shorter (974bp). The differences in transcripts length is a result of two polyadenylation sites present in the 3'UTR resulting in two transcription termination signals. Transcript sequences encoded one unique protein that can be classified as type I CHH subfamily because of the 4 exons and 3 introns structure, although the CPRP region is not-well conserved and there is no amidation in the C-terminal of the deduced amino acid sequence. Furthermore, there is a glycine inserted in the mature peptide not at position 12 as in type II CHHs but after amino acid 31 and the phylogenetic analysis did not group the peptide within type I, but closer to type II CHHs. We demonstrated by endpoint-PCR, qPCR, and in situ hybridization (ISH), that this gene is expressed in neuroendocrine organs known to express CHHs in penaeid shrimp, including X-organ and optic nerve in eyestalk, supraesophageal ganglion (SoG), but it is also expressed in other organs as gill, gut, pericardial cavity, as well as in terminal ampoule or spermatophore and vas deferens of males. PMID- 26861612 TI - Investigation of vital pathogenic target orotate phosphoribosyltransferases (OPRTase) from Thermus thermophilus HB8: Phylogenetic and molecular modeling approach. AB - Biosynthesis pathways of pyrimidine and purine are shown to play an important role in regular cellular activities. The biosynthesis can occur either through de novo or salvage pathways based on the requirement of the cell. The pyrimidine biosynthesis pathway has been linked to several disorders and various autoimmune diseases. Orotate phosphoribosyl transferase (OPRTase) is an important enzyme which catalyzes the conversion of orotate to orotate monophosphate in the fifth step of pyrimidine biosynthesis. Phylogenetic analysis of 228 OPRTase sequences shows the distribution of proteins across different living forms of life. High structural similarities between Thermusthermophilus and other organisms kindled us to concentrate on OPRTase as an anti-pathogenic target. In this study, a homology model of OPRTase was constructed using 2P1Z as a template. About 100 ns molecular dynamics simulation was performed to investigate the conformational stability and dynamic patterns of the protein. The amino acid residues (Met1, Asp2, Glu43, Ala44, Glu47, Lys51, Ala157 and Leu158) lining in the binding site were predicted using SiteMap. Further, structure based virtual screening was performed on the predicted binding site using ChemBridge, Asinex, Binding, NCI, TosLab and Zinc databases. Compounds retrieved from the screening collections were manually clustered. The resultant protein-ligand complexes were subjected to molecular dynamics simulations, which further validates the binding modes of the hits. The study may provide better insight for designing potent anti-pathogenic agent. PMID- 26861613 TI - Interleukin-1Ra rs2234663 and Interleukin-4 rs79071878 Polymorphisms in Familial Mediterranean Fever. AB - OBJECTIVE: Familial Mediterranean Fever (FMF) is an autosomal recessively inherited auto inflammatory disorder. MEFV gene, causing FMF, encodes pyrin that is associated with the interleukin-1 (IL-1) related inflammation cascade. The aim of this study was to investigate the relationship of interleukin-1 receptor antagonist (IL-1Ra) and interleukin-4 (IL-4) polymorphisms with the risk of FMF in the Turkish population. METHODS: This study included 160 patients with FMF (74 men, 86 women) and 120 healthy controls (50 men, 70 women), respectively. Genotyping of IL-1Ra rs2234663 polymorphism was evaluated by gel electrophoresis after polymerase chain reaction (PCR). The IL-4 rs79071878 polymorphism was determined by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis. The results of analyses were evaluated for statistical significance. RESULTS: There was no significant difference in IL-1Ra genotype and allele distributions between FMF and the control groups (p>0.05). However, a significant association was observed between FMF patients and control groups according to IL 4 genotype distribution (p=0.016), but no association was found in the allelic frequency of IL-4 between FMF patients and the controls (p>0.05, OR: 1.131, CI 95%: 0.71-1.81). CONCLUSIONS: The IL-4 rs79071878 polymorphism, was associated whereas the IL-1Ra rs2234663 polymorphism was not associated with FMF risk in the Turkish population. Larger studies with different ethnicities are needed to determine the impact of IL-1Ra and IL-4 polymorphism on the risk of developing FMF. PMID- 26861615 TI - Gravure-printed interdigital microsupercapacitors on a flexible polyimide substrate using crumpled graphene ink. AB - In this paper, we demonstrate gravure printing of crumpled graphene ink to obtain a highly porous pattern of interdigitated electrodes, leading to an interdigital microsupercapacitor (MSC) on a flexible polyimide substrate. During the process of synthesizing crumpled graphene ink, Mg(OH)2 nanosheets as nanospacers were inserted into graphite oxide layers, resulting in sufficient crumples in graphene nanosheets to prevent the graphene sheets from restacking to enhance the ion transport and expose the electrochemical active area with oxygen-containing groups to provide more pseudo-capacitance. The gravure-printed interdigital MSCs achieved a high energy density (1.41 mW h cm(-3) at 25 mW cm(-3)) and high power density (0.35 mW h cm(-3) at 300 mW cm(-3)), respectively. Additionally, a liquid crystal display was driven by the two serial and two parallel connected MSCs for 35 s after charging for 3 s. PMID- 26861614 TI - Disease-specific anxiety symptomatology in Parkinson's disease. AB - BACKGROUND: Symptoms of anxiety relating to Parkinson's disease (PD) occur commonly and include symptomatology associated with motor disability and complications arising from PD medication. However, there have been relatively few attempts to profile such disease-specific anxiety symptoms in PD. Consequently, anxiety in PD is underdiagnosed and undertreated. The present study characterizes PD-related anxiety symptoms to assist with the more accurate assessment and treatment of anxiety in PD. METHODS: Ninety non-demented PD patients underwent a semi-structured diagnostic assessment targeting anxiety symptoms using relevant sections of the Mini International Neuropsychiatric Interview (MINI-plus). In addition, they were assessed for the presence of 30 PD-related anxiety symptoms derived from the literature, the clinical experience of an expert panel and the PD Anxiety-Motor Complications Questionnaire (PDAMCQ). The onset of anxiety in relation to the diagnosis of PD was determined. RESULTS: Frequent (>25%) PD specific anxiety symptoms included distress, worry, fear, agitation, embarrassment, and social withdrawal due to motor symptoms and PD medication complications, and were experienced more commonly in patients meeting DSM-IV criteria for an anxiety disorder. The onset of common anxiety disorders was observed equally before and after a diagnosis of PD. Patients in a residual group of Anxiety Not Otherwise Specified had an onset of anxiety after a diagnosis of PD. CONCLUSION: Careful characterization of PD-specific anxiety symptomatology provides a basis for conceptualizing anxiety and assists with the development of a new PD-specific measure to accurately assess anxiety in PD. PMID- 26861616 TI - First finding of the parasitic fungus Hesperomyces virescens (Laboulbeniales) on native and invasive ladybirds (Coleoptera, Coccinellidae) in South Africa. AB - Hesperomyces virescens is a fungal ectoparasite (Laboulbeniales) that infects adult ladybirds. Research has recently focused on this parasite due to the discovery of its prevalence on the globally invasive harlequin ladybird Harmonia axyridis and for its potential use in studies of co-evolution and pathogen spread. We collected adults from ten species of ladybirds in the Western Cape Province, South Africa, and screened for the presence of H. virescens. Infections with H. virescens were found in the samples of two species, H. axyridis and the native Cheilomenes propinqua. This marks the first record of H. virescens on H. axyridis from the African continent and the first record on Cheilomenes worldwide. PMID- 26861617 TI - Testing predictive control of movement in children with developmental coordination disorder using converging operations. AB - Recent systematic reviews (Wilson et al., 2013, Dev. Med. Child Neurol., 55, 217; Adams et al., 2014, Neurosci. Biobehav. Rev., 47C, 225) suggest that a common underlying problem in developmental coordination disorder (DCD) is the internal modelling deficit. The study presented here is the first to test this hypothesis using a within-subject design, assessing motor imagery, action planning, and rapid online control (ROC) in a sample of children screened rigorously for DCD. Participants were 66 children; 33 children (26 boys and seven girls) aged 6-11 years in the DCD group and 33 controls (gender and age matched). Motor imagery was assessed with the hand rotation task (HRT), action planning with an end-state comfort effect test, and ROC with the double-step pointing task. Results showed that children with DCD were slower and less accurate than controls in the HRT. Reduced forward planning for comfortable end-state was also shown in DCD. Finally, no group differences were found on the ROC task. Collectively, children with DCD manifest deficits in the internal modelling of movements, but this varies under different task constraints, particularly those related to movement complexity. PMID- 26861618 TI - The evolutionary ecology of transmissible cancers. AB - Transmissible tumours, while rare, present a fascinating opportunity to examine the evolutionary dynamics of cancer as both an infectious agent and an exotic, invasive species. Only three naturally-occurring transmissible cancers have been observed so far in the wild: Tasmanian devil facial tumour diseases, canine transmissible venereal tumour, and clam leukaemia. Here, we define four conditions that are necessary and sufficient for direct passage of cancer cells between either vertebrate or invertebrate hosts. Successful transmission requires environment and behaviours that facilitate transfer of tumour cells between hosts including: tumour tissue properties that promote shedding of large numbers of malignant cells, tumour cell plasticity that permits their survival during transmission and growth in a new host, and a 'permissible' host or host tissue. This rare confluence of multiple host- and tumour cell-traits both explains the rarity of tumour cell transmission and provides novel insights into the dynamics that both promote and constrain their growth. PMID- 26861619 TI - Analysis of uncommon norovirus recombinants from Manaus, Amazon region, Brazil: GII.P22/GII.5, GII.P7/GII.6 and GII.Pg/GII.1. AB - Norovirus (NoV) is responsible for outbreaks and sporadic cases of nonbacterial acute gastroenteritis in humans worldwide. The virus consists of small round particles containing a single-stranded RNA genome that is divided into three Open Reading Frames. NoV evolves via mechanisms of antigenic drift and recombination, which lead to the emergence of new strains that are capable of causing global epidemics. Recombination usually occurs in the ORF1/ORF2 overlapping region and generates strains with different genotypes in the polymerase and capsid region. The primary objective of this study was to analyze recombination in positive-NoV samples. Specimens were collected during 2011, 2012 and 2014, from children under two years of age presenting gastrointestinal symptoms such as vomiting and diarrhea. The partial polymerase (B region), capsid (D region) genes and the ORF1 ORF2 overlap regions were sequenced in each sample. The recombinant analyses were performed in the Simplot software v.3.5.1 and RDP4 Beta v. 4.6 program. These analyses showed that GII.Pg/GII.1, GII.P7/GII.6, and GII.P22/GII.5 were recombinant strains. To our knowledge, this is the first time that the GII.P22/GII.5 and GII.Pg/GII.1 strains were described in South America and the GII.P7/GII.6 was detected in Northern of Brazil. PMID- 26861620 TI - Prevalence and genotyping of Giardia duodenalis isolated from sheep in Henan Province, central China. AB - Giardia duodenalis is a gastrointestinal protozoan that infects sheep. It is a well-known zoonotic pathogen and sheep have been implicated as a source of human infection. However, there have been few studies of its potential threat to public health in China. We used a multilocus analysis of the beta-giardin (bg), glutamate dehydrogenase (gdh), and triose phosphate isomerase (tpi) genes to examine the occurrence and genotype distribution of G. duodenalis in sheep in China. In total, 716 fresh faecal specimens, including 89 from pre-weaned lambs (<3 months old) and 627 from post-weaned sheep (>3 months old) from nine intensive sheep farms in Henan Province, China, were examined for Giardia cysts with microscopy. Of these specimens, 6.65% (47/716; 99% CI: 6.2%-6.92%) from five farms were positive for G. duodenalis. The infection rate was significantly higher in pre-weaned lambs than in post-weaned sheep (12.36% versus 5.74%, respectively; P<0.05). Infection rates ranged from 2.8% to 17.2% on the G. duodenalis-positive farms. All G. duodenalis-positive samples were assayed with PCR followed by sequencing at the three gene loci investigated in this study. As a result, two assemblages were detected: assemblage A (n=5) and assemblage E (n=31), with some mixed E and A infections (n=3). The ratios of assemblage A to assemblage E on the different successfully sequenced G. duodenalis-positive farms were 0:1, 3:14, 1:4, and 1:12. Two new tpi sequences and one new gdh sequence were identified. Multilocus genotyping yielded seven multilocus genotypes (MLGs): one new assemblage A MLG and six assemblage E MLGs. In the phylogenetic analysis, the assemblage A MLG was more closely related to AI than to AII or AIII. The detection of G. duodenalis assemblage A in sheep has public health implications, although G. duodenalis assemblage E was predominant. The data provide basic information for control of giardiasis in human and sheep in Henan province, central China. PMID- 26861621 TI - Clinical characteristics of the patients with bacteremia due to Moraxella catarrhalis in children: a case-control study. AB - BACKGROUND: Invasive diseases due to Moraxella catarrhalis are rare in children, even in immunocompromised hosts. Therefore, data regarding clinical characteristics and risk factors of such patients are limited. The aim of this study is to compare the clinical characteristics of patients with bacteremia due to Moraxella catarrhalis against those with bacteremia due to Streptococcus pneumoniae and Haemophilus influenzae. METHODS: We performed a retrospective case control study to compare patients younger than 18 years of age with positive blood cultures for the three pathogens between June 2008 and May 2014 at our institution. Data regarding patients' demographics and clinical course were collected from their medical records. Three group comparisons, with M. catarrhalis as reference, were made by the Fisher's exact test and Wilcoxon rank sum test for discrete and continuous variables, respectively. RESULTS: There were eight cases of M. catarrhalis, 110 cases of S. pneumoniae (105 patients) and 22 cases of H. influenzae. The M. catarrhalis group consisted of six females (75 %) with a mean age of 16 months. The majority of patients (7/8, 88 %) had underlying diseases; however, only one was immunocompromised. Characteristically, six patients (75 %) had medical devices including trans-nasal devices (5/8, 63 %). Univariate analysis revealed that underlying conditions (P = 0.005), trans-nasal devices (P < 0.001), and lower body weight (P = 0.016) and low white blood cell count (P = 0.011) at the onset of illness were associated with the M. catarrhalis group compared to the S. pneumoniae group. Meanwhile, the higher rates of the patients with underlying conditions and trans-nasal devices were associated with the M. catarrhalis group compared to the H. influenzae group (P = 0.039, P < 0.001, respectively). CONCLUSIONS: The presence of underlying conditions, particularly in those with trans-nasal devices, were characteristic features of patients with bacteremia due to M. catarrhalis. PMID- 26861622 TI - Palliative treatment of anal fistulas in Crohn's disease. AB - INTRODUCTION: Anal fistula in Crohn's disease is frequently an intractable condition. Methods of treatment are still debated because the results of various procedures are unsatisfactory. Available studies show that results can be improved using a combination of surgical and medical methods. Most patients undergo rather palliative than radical, curative procedures such as incision and drainage of abscesses and prolonged non-cutting seton placement. Surgery is combined today with biological therapy using infliximab, a murine-human chimeric monoclonal antibody against TNF-alpha or adalimumab a human monoclonal anti-TNF antibody to increase the healing process and in an attempt to prevent fistula recurrence. METHODS: Medical records of 23 patients who were treated for anal fistulas in Crohn's disease between 2012 and 2014 were retrospectively evaluated. RESULTS: There were 10 (43%) males and 13 females. The mean age was 39 years (range 29-60 years). Median duration of CD before present treatment was 6 years (range 1-15 years). Closure of all fistulas in 6 months was achieved in eight (35%) patients, whereas reduction of at least 50% from base line in the number of draining fistulas occurred in four (17%) patients. CONCLUSION: Palliative and combined therapy for anal fistulas in Crohn's disease with surgery and infliximab or adalimumab therapy is an effective treatment for some patients. PMID- 26861623 TI - Mesenchymal stem cells and their secreted molecules predominantly ameliorate fulminant hepatic failure and chronic liver fibrosis in mice respectively. AB - BACKGROUND: Orthotopic liver transplantation is the only effective treatment for liver failure but limited with shortage of available donor organs. Recent studies show promising results of mesenchymal stem cells (MSCs)-based therapies. METHODS: We systematically investigate the therapeutic effects of MSCs or MSC-conditioned medium (MSC-CM) in ameliorating fulminant hepatic failure (FHF) and chronic liver fibrosis in mice. In addition, extensive flow cytometry analysis of spleens from vehicle and MSC- and MSC-CM-treated mice was applied to reveal the alteration of inflammatory state. RESULTS: In FHF model, MSCs treatment reduced remarkably the death incidents; the analysis of gross histopathology showed that control livers were soft and shrunken with extensive extravasated blood, which was gradually reduced at later time points, while MSC-treated livers showed gross pathological changes, even 24 h after MSC infusion, and hematoxylin and eosin staining revealed dramatical hepatocellular death with cytoplasmic vacuolization suppressed by MSCs treatment; flow cytometry analysis of total lymphocytes showed that macrophages (F4/80) infiltrated into control livers more than MSC-treated livers; by contrast, MSC-CM partially ameliorates FHF. In chronic liver injury model, MSC and MSC-CM both suppressed fibrogenesis and necroinflammatory, and the later was better; activation of hepatic stellate cells (alpha-SMA) was inhibited; glycogen synthesis and storage (indicated by periodic acid-Schiff -staining) was improved; liver regeneration (Ki67) was promoted while liver apoptosis (TUNEL) was reduced. In the in vitro, MSCs promote macrophage line RAW264.7 apoptosis and MSC-CM promotes apoptosis and inhibits proliferation of HSC line LX-2. We also found that MSCs and MSC-CM could improve spleen; MSC-CM increased levels of Th2 and Treg cells, and reduced levels of Th17 cells, whereas levels of Th1 cells were unchanged; comparatively, MSC treatment did not affect Th17 and Treg cells and only slightly alters inflammatory state; MSC and MSC-CM treatment both substantially down-regulated macrophages in the spleens. CONCLUSION: Both MSCs and MSC-CM exert therapeutic effects by acting on various key cells during the pathogenesis of FHF and chronic fibrosis, stimulating hepatocyte proliferation and suppressing apoptosis, down-regulating infiltrating macrophages, converting CD4(+) T lymphocyte system into an anti-inflammatory state, and facilitating hepatic stellate cell death. PMID- 26861624 TI - Key role of lipid management in nitrogen and aroma metabolism in an evolved wine yeast strain. AB - BACKGROUND: Fermentative aromas play a key role in the organoleptic profile of young wines. Their production depends both on yeast strain and fermentation conditions. A present-day trend in the wine industry consists in developing new strains with aromatic properties using adaptive evolution approaches. An evolved strain, AffinityTM ECA5, overproducing esters, was recently obtained. In this study, dynamics of nitrogen consumption and of the fermentative aroma synthesis of the evolved and its ancestral strains were compared and coupled with a transcriptomic analysis approach to better understand the metabolic reshaping of AffinityTM ECA5. RESULTS: Nitrogen assimilation was different between the two strains, particularly amino acids transported by carriers regulated by nitrogen catabolite repression. We also observed differences in the kinetics of fermentative aroma production, especially in the bioconversion of higher alcohols into acetate esters. Finally, transcriptomic data showed that the enhanced bioconversion into acetate esters by the evolved strain was associated with the repression of genes involved in sterol biosynthesis rather than an enhanced expression of ATF1 and ATF2 (genes coding for the enzymes responsible for the synthesis of acetate esters from higher alcohols). CONCLUSIONS: An integrated approach to yeast metabolism-combining transcriptomic analyses and online monitoring data-showed differences between the two strains at different levels. Differences in nitrogen source consumption were observed suggesting modifications of NCR in the evolved strain. Moreover, the evolved strain showed a different way of managing the lipid source, which notably affected the production of acetate esters, likely because of a greater availability of acetyl-CoA for the evolved strain. PMID- 26861625 TI - Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. AB - Most RNAs generated by the human genome have no protein-coding ability and are termed non-coding RNAs. Among these include circular RNAs, which include exonic circular RNAs (circRNA), mainly found in the cytoplasm, and intronic RNAs (ciRNA), predominantly detected in the nucleus. The biological functions of circular RNAs remain largely unknown, although ciRNAs have been reported to promote gene transcription, while circRNAs may function as microRNA sponges. We demonstrate that the circular RNA circ-Foxo3 was highly expressed in non-cancer cells and were associated with cell cycle progression. Silencing endogenous circ Foxo3 promoted cell proliferation. Ectopic expression of circ-Foxo3 repressed cell cycle progression by binding to the cell cycle proteins cyclin-dependent kinase 2 (also known as cell division protein kinase 2 or CDK2) and cyclin dependent kinase inhibitor 1 (or p21), resulting in the formation of a ternary complex. Normally, CDK2 interacts with cyclin A and cyclin E to facilitate cell cycle entry, while p21works to inhibit these interactions and arrest cell cycle progression. The formation of this circ-Foxo3-p21-CDK2 ternary complex arrested the function of CDK2 and blocked cell cycle progression. PMID- 26861627 TI - Transcriptome dynamics of the microRNA inhibition response. PMID- 26861626 TI - The ISW1 and CHD1 ATP-dependent chromatin remodelers compete to set nucleosome spacing in vivo. AB - Adenosine triphosphate-dependent chromatin remodeling machines play a central role in gene regulation by manipulating chromatin structure. Most genes have a nucleosome-depleted region at the promoter and an array of regularly spaced nucleosomes phased relative to the transcription start site. In vitro, the three known yeast nucleosome spacing enzymes (CHD1, ISW1 and ISW2) form arrays with different spacing. We used genome-wide nucleosome sequencing to determine whether these enzymes space nucleosomes differently in vivo We find that CHD1 and ISW1 compete to set the spacing on most genes, such that CHD1 dominates genes with shorter spacing and ISW1 dominates genes with longer spacing. In contrast, ISW2 plays a minor role, limited to transcriptionally inactive genes. Heavily transcribed genes show weak phasing and extreme spacing, either very short or very long, and are depleted of linker histone (H1). Genes with longer spacing are enriched in H1, which directs chromatin folding. We propose that CHD1 directs short spacing, resulting in eviction of H1 and chromatin unfolding, whereas ISW1 directs longer spacing, allowing H1 to bind and condense the chromatin. Thus, competition between the two remodelers to set the spacing on each gene may result in a highly dynamic chromatin structure. PMID- 26861629 TI - Selective connectivity of dopamine neurons projecting to the posterior striatum. PMID- 26861630 TI - Event-based proactive interference in rhesus monkeys. AB - Three rhesus monkeys (Macaca mulatta) were tested in a same/different memory task for proactive interference (PI) from prior trials. PI occurs when a previous sample stimulus appears as a test stimulus on a later trial, does not match the current sample stimulus, and the wrong response "same" is made. Trial-unique pictures (scenes, objects, animals, etc.) were used on most trials, except on trials where the test stimulus matched potentially interfering sample stimulus from a prior trial (1, 2, 4, 8, or 16 trials prior). Greater interference occurred when fewer trials separated interference and test. PI functions showed a continuum of interference. Delays between sample and test stimuli and intertrial intervals were manipulated to test how PI might vary as a function of elapsed time. Contrary to a similar study with pigeons, these time manipulations had no discernable effect on the monkey's PI, as shown by compete overlap of PI functions with no statistical differences or interactions. These results suggested that interference was strictly based upon the number of intervening events (trials with other pictures) without regard to elapsed time. The monkeys' apparent event-based interference was further supported by retesting with a novel set of 1,024 pictures. PI from novel pictures 1 or 2 trials prior was greater than from familiar pictures, a familiar set of 1,024 pictures. Moreover, when potentially interfering novel stimuli were 16 trials prior, performance accuracy was actually greater than accuracy on baseline trials (no interference), suggesting that remembering stimuli from 16 trials prior was a cue that this stimulus was not the sample stimulus on the current trial-a somewhat surprising conclusion particularly given monkeys. PMID- 26861632 TI - Attitudes and intended behaviour to mental disorders and associated factors in catalan population, Spain: cross-sectional population-based survey. AB - BACKGROUND: Mental disorders have a huge impact on the European population. Two of the main causes of this impact are stigma and discrimination. The aim of this paper is to assess the stigma regarding mental disorder in Catalonia and to explore factors associated with stigma. METHODS: Cross-sectional population-based survey of a representative sample of non-institutionalized adult population (n = 1872). We evaluated attitudes (CAMI: Authoritarianism, Benevolence and Support to Community Mental Health care) and intended behaviour (RIBS) regarding mental disorder and experience of discrimination. Higher scores showed more favourable attitudes and intended behavior. Mean values and percentiles of the scales were calculated. Multivariable regression models were used to assess factors associated with stigma. RESULTS: Mean authoritarianism, benevolence and support to community mental health scores corresponded to the 66th, 90th and 78th percentile, respectively. Mean RIBS score corresponded to the 76th percentile. More favourable attitudes were associated with being male, younger, having a higher education, being Spanish, having suffered a mental disorder and having contact with a person with a mental disorder.Similarly, more favourable intended behaviour was associated with being younger, having secondary education, having Spanish nationality, belonging to a higher social class and having contact with a person with a mental disorder. People with depression or anxiety showed lower discrimination experiences than people with other mental disorders. CONCLUSIONS: The levels of stigma were generally low among the Catalan population. However, efforts should be made to decrease stigma related to authoritarianism. Interventions addressed to reducing stigma should take into account other mental disorders apart from depression or anxiety. They should be focused on older, immigrant population, people with lower educational attainment and people who have not had contact with someone with a mental disorder. PMID- 26861634 TI - [Problems breathing through the nose and diplopic images]. PMID- 26861635 TI - Postoperative complications in the treatment of rectal neoplasia by transanal endoscopic microsurgery: a prospective study of risk factors and time course. AB - PURPOSE: Transanal endoscopic microsurgery (TEM) is a safe and efficient minimally invasive treatment for rectal benign and early malignant neoplasia, but postoperative complications may be severe. We aimed to evaluate the risk factors related to the incidence, severity, and time course of postoperative complications of TEM. METHODS: This is a prospective study of postoperative complications in 53 patients (>18 years old) with benign or early rectal neoplasia who underwent TEM with curative intention or, for higher stages, palliation. Outcome measures included age, sex, American Society of Anesthesiologists score, neoadjuvant chemoradiotherapy, lesion height and size, pathologic margins, tumor histology, and suture type. RESULTS: Overall morbidity was 50 %. Temporary fecal incontinence was the most frequent complication (17.3 %). Complication rates of Clavien-Dindo grades I and II were 21.1 % and those of grades III and IV 3.8 %. Of patients with complications, more had lesions under the first rectal valve than over the first valve (61.54 % vs 38.46 %, p = 0.04). Patients submitted to chemoradiotherapy had a 24-fold greater chance of presenting grade II complications (p = 0.002). When the surgical defect was treated using the TEM device to perform the suture, the chance of having grade III complications was reduced 16-fold (p = 0.04). Fifty-three percent of complications occurred in the first 10 days and 95 % within 20 days. CONCLUSIONS: Postoperative complications after transanal endoscopic microsurgery for the treatment of rectal neoplasia are frequent, acceptable, and usually controllable with pharmacologic treatment. Over time the nature of complications is continuous, centered on the first 20 days after surgery. PMID- 26861636 TI - Difficult defecation in constipated patients and its relationship to colonic disorders. AB - BACKGROUND: The importance in constipated subjects of having difficult defecation is poorly known. According to the Rome III criteria, constipated patients are classified as having either irritable bowel syndrome with constipation or functional constipation, depending on the presence and characteristics of abdominal pain. But, the Rome III criteria also identify another group of patients, labeled as suffering from functional anorectal disorders. Within this group, two complaints are akin to being constipated, but not labeled so: having dyssynergic defecation or inadequate defecation. OBJECTIVE: The aim of this study was to search for an association between difficult defecation and colonic transit abnormalities in constipated patients and, thus, shed some light on the definition of constipation according to the Rome III criteria. PATIENTS: Four hundred four consecutive patients (81% female), aged 44.9 +/- 16.6 years, with a BMI of 25.5 +/- 6.4 kg/m(2) (mean +/- SD), suffering from chronic constipation were included in the present study. After filling out a standard Rome III questionnaire, patients were classified as suffering from an irritable bowel syndrome with constipation or functional constipation. In addition, they were classified as complaining of difficult defecation or not. Patients completed the Bristol Stool Form Scale as well as visual analogue scales for constipation, bloating, and abdominal pain. The colonic transit time was measured using radiopaque markers and analyzed according to three sites: the right colon, the left colon, and the rectosigmoid area. RESULTS: Difficult defecation is more frequent in patients with irritable bowel syndrome with constipation (84%) than in patients with functional constipation (68%). It is associated with an increase in constipation and abdominal pain scores on Likert scales, and a longer oroanal transit time, due to a delay in the left part of the colon. CONCLUSIONS: This study demonstrates that difficult defecation is part of a more generalized colorectal dysfunction in both irritable bowel syndrome and in functional constipation patients with an overlap of symptomatology. It also demonstrates the relative inadequacy of the Rome III criteria to describe the relationship between constipation and difficult defecation. PMID- 26861637 TI - SaFaRI: sacral nerve stimulation versus the Fenix(r) magnetic sphincter augmentation for adult faecal incontinence: a randomised investigation. PMID- 26861638 TI - Indian Medical Association backs lifting ban on sex testing. PMID- 26861640 TI - Erratum to: Individualizing propofol dosage: a multivariate linear model approach. PMID- 26861639 TI - Passive continuous positive airway pressure ventilation during cardiopulmonary resuscitation: a randomized cross-over manikin simulation study. AB - While controlled ventilation is most frequently used during cardiopulmonary resuscitation (CPR), the application of continuous positive airway pressure (CPAP) and passive ventilation of the lung synchronously with chest compressions and decompressions might represent a promising alternative approach. One benefit of CPAP during CPR is the reduction of peak airway pressures and therefore a potential enhancement in haemodynamics. We therefore evaluated the tidal volumes and airway pressures achieved during CPAP-CPR. During CPR with the LUCASTM 2 compression device, a manikin model was passively ventilated at CPAP levels of 5, 10, 20 and 30 hPa with the Boussignac tracheal tube and the ventilators Evita(r) V500, Medumat(r) Transport, Oxylator(r) EMX, Oxylog(r) 2000, Oxylog(r) 3000, Primus(r) and Servo(r)-i as well as the Wenoll(r) diver rescue system. Tidal volumes and airway pressures during CPAP-CPR were recorded and analyzed. Tidal volumes during CPAP-CPR were higher than during compression-only CPR without positive airway pressure. The passively generated tidal volumes increased with increasing CPAP levels and were significantly influenced by the ventilators used. During ventilation at 20 hPa CPAP via a tracheal tube, the mean tidal volumes ranged from 125 ml (Medumat(r)) to 309 ml (Wenoll(r)) and the peak airway pressures from 23 hPa (Primus(r)) to 49 hPa (Oxylog(r) 3000). Transport ventilators generated lower tidal volumes than intensive care ventilators or closed-circuit systems. Peak airway pressures during CPAP-CPR were lower than those during controlled ventilation CPR reported in literature. High peak airway pressures are known to limit the applicability of ventilation via facemask or via supraglottic airway devices and may adversely affect haemodynamics. Hence, the application of ventilators generating high tidal volumes with low peak airway pressures appears desirable during CPAP-CPR. The limited CPAP-CPR capabilities of transport ventilators in our study might be prerequisite for future developments of transport ventilators. PMID- 26861641 TI - Heavy metal removal using nanoscale zero-valent iron (nZVI): Theory and application. AB - Treatment of wastewater containing heavy metals requires considerations on simultaneous removal of different ions, system reliability and quick separation of reaction products. In this work, we demonstrate that nanoscale zero-valent iron (nZVI) is an ideal reagent for removing heavy metals from wastewater. Batch experiments show that nZVI is able to perform simultaneous removal of different heavy metals and arsenic; reactive nZVI in uniform dispersion brings rapid changes in solution Eh, enabling a facile way for reaction regulation. Microscope characterizations and settling experiments suggest that nZVI serves as solid seeds that facilitate products separation. A treatment process consisting of Eh controlled nZVI reaction, gravitational separation and nZVI recirculation is then demonstrated. Long-term (>12 months) operation shows that the process achieves >99.5% removal of As, Cu and a number of other toxic elements. The Eh-controlled reaction system sustains a highly-reducing condition in reactor and reduces nZVI dosage. The process produces effluent of stable quality that meets local discharge guidelines. The gravitational separator shows high efficacy of nZVI recovery and the recirculation improves nZVI material efficiency, resulting in extraordinarily high removal capacities ((245mg As+226 mg-Cu)/g-nZVI). The work provides proof that nanomaterials can offer truly green and cost-effective solutions for wastewater treatment. PMID- 26861642 TI - Clinical significance of microRNA-34b expression in pediatric acute leukemia. AB - The present study aimed to explore the function of miR-34b promoter methylation in cell proliferation in children's acute leukemia. Quantitative PCR and methylation-specific PCR were performed to measure the levels of miR-34b and its promoter methylation in normal cells, eight leukemia cell lines as well as primary leukemic cells isolated from patients newly diagnosed with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) and mixed lymphocytic lymphoma. miR-34b levels in leukemia cell lines and primary leukemic cells were significantly lower than those in normal cells. The miR-34b promoter was found to be methylated in all leukemia cell lines, 24 of 31 ALL patients and 8 of 19 AML patients, but not in the 23 normal controls. miR-34b expression and methylation of its promoter were not associated with most clinical parameters assessed; however, miR-34b levels in prednisone-sensitive ALL were significantly different from those in insensitive ALL. A cell counting kit-8 assay showed that transfection of miR-34b mimics into K562 cells inhibited their proliferation. Furthermore, treatment with the demethylating agent 5-aza-2-deoxycytidine significantly enhanced miR-34b expression levels and decreased the methylation status of its promoter in HL-60 and K562 cells. In conclusion, the results of the present study indicated that in pediatric leukemia cells and leukemia cell lines, the expression of miR-34b is inhibited by methylation of its promoter, which impairs the restraining effects of miR-34b on cell proliferation. It was also indicated that the expression of miR-34b in ALL patients may affect their response to early treatments. PMID- 26861643 TI - Depressed Mood During Early to Middle Adolescence: A Bi-national Longitudinal Study of the Unique Impact of Family Conflict. AB - Adolescent depressed mood is related to the development of subsequent mental health problems, and family problems have been linked to adolescent depression. Longitudinal research on adolescent depressed mood is needed to establish the unique impact of family problems independent of other potential drivers. This study tested the extent to which family conflict exacerbates depressed mood during adolescence, independent of changes in depressed mood over time, academic performance, bullying victimization, negative cognitive style, and gender. Students (13 years old) participated in a three-wave bi-national study (n = 961 from the State of Washington, United States, n = 981 from Victoria, Australia; 98 % retention, 51 % female in each sample). The model was cross-lagged and controlled for the autocorrelation of depressed mood, negative cognitive style, academic failure, and bullying victimization. Family conflict partially predicted changes in depressed mood independent of changes in depressed mood over time and the other controls. There was also evidence that family conflict and adolescent depressed mood are reciprocally related over time. The findings were closely replicated across the two samples. The study identifies potential points of intervention to interrupt the progression of depressed mood in early to middle adolescence. PMID- 26861645 TI - Mitochondrial Signaling and Hepatocellular Carcinoma: Molecular Mechanisms and Therapeutic Implications. AB - BACKGROUND: Molecular pathogenesis of hepatocellular carcinoma is complex and implies a multistep process involving different genetic and epigenetic alterations, as well as altered molecular pathways. Among these features, oxidative stress and mitochondria dysfunction represent an important trigger to hepatocarcinogenesis regardless of underlying liver disease etiology. An important part of the actual cancer research is focused on the molecular mechanisms and the signaling pathways involved in the process of so called "mitochondrial malignancy". METHOD: Aim of this review is to summarize the main molecular mechanisms and the pathological consequences of oxidative stress and mitochondrial dysfunction in liver cancer. Furthermore, an up-to-date insight in therapeutic implications of the aforementioned processes is consistently developed. A literature search was conducted using PubMed until October 2015, based on English language journals. RESULTS: Mitochondrial dysfunction may dramatically alter cell growth and proliferation by means of several "retrograde" mitochondria-nucleus signaling pathways, all of which have been shown to play a significant role in hepatocarcinogenesis. Nuclear oncogenes and tumor suppressors alike regulate mitochondrial turnover and function in a thick cross-talk whose role is fundamental in human oncology. CONCLUSION: The current knowledge on the role of mitochondrial signaling and oxidative stress in hepatocarcinogenesis seems to support the use of antioxidant agents in hepatocarcinoma patients, for instance in the adjuvant setting after radical treatments where their favorable cost-effective and safety profile may enable long-terms therapies aimed at preventing tumor recurrence. Data from randomized-controlled trials are warranted in order to confirm these promising results. PMID- 26861646 TI - Lipoprotein Like Nanoparticles Used in Drug and Gene Delivery. AB - BACKGROUND: Native lipoproteins as nanoparticulate drug delivery systems have gained considerable attention in recent years. This is due to their biocompatibility, being endogenous, no triggering the immunological responses, relatively long half-life in the circulation, simple diffusion from vascular to extravascular compartments due to their nanometric particle size, potentially targeting capability to cellular receptors, simple preparative processes in the reconstituted forms, easy functionalization and high capacity for drug loading. Clinical application of many therapeutic agents like anticancer drugs and genes is hampered due to their susceptibility to degradation and difficult delivery into cells. Several nanoparticle platforms for siRNA delivery have been developed to overcome the major limitations facing the therapeutic uses of bioactive therapeutic agents. METHODS: This review covers a broad spectrum of lipoproteins as non-viral drug and gene delivery systems. These nanoparticles are developed for enhanced cellular uptake and specially targeted gene silencing in vitro and in vivo and their characteristics and opportunities for clinical applications of therapeutic agents are discussed in this article. Various types of lipoprotein nanovectors including: natural and modified lipoproteins used to deliver drugs, bioactive and genetic materials are introduced and the development of theranostics and combinational treatments are also discussed. RESULTS: The unique physicochemical properties of lipoproteins as natural nanostructures in biological systems and their structural diversity, including chylomicrons, VLDL, LDL and HDL, has caused their utility as potent pharmaceutical carriers. CONCLUSION: According to the literatures, different lipoproteins especially the artificial lipoproteins, reconstituted and modified ones have potential to be used in targeted delivery of therapeutic agents to the tumors and effective delivery of the corresponding genetic and other bioactive components involving in diseases. PMID- 26861644 TI - Stability Characterization of a Polysorbate 80-Dimethyl Trisulfide Formulation, a Cyanide Antidote Candidate. AB - Novel cyanide countermeasures are needed for cases of a mass-exposure cyanide emergency. A lead candidate compound is dimethyl trisulfide (DMTS), which acts as a sulfur donor for rhodanese, thereby assisting the conversion of cyanide into thiocyanate. DMTS is a safe compound for consumption and, in a 15% polysorbate 80 (DMTS-PS80) formulation, has demonstrated good efficacy against cyanide poisoning in several animal models. We performed a stability study that investigated the effect of temperature, location of formulation preparation, and pH under buffered conditions. We found that while the stability of the DMTS component was fairly independent of which laboratory prepared the formulation, the concentration of DMTS in the formulation was reduced 36-58% over the course of 29 weeks when stored at room temperature. This loss typically increased with increasing temperatures, although we did not find statistical differences between the stability at different storage temperatures in all formulations. Further, we found that addition of a light buffer negatively impacted the stability, whereas the pH of that buffer did not impact stability. We investigated the factors behind the reduction of DMTS over time using various techniques, and we suggest that the instability of the formulation is governed at least partially by precipitation and evaporation, although a combination of factors is likely involved. PMID- 26861647 TI - Nanoparticles Based on Plasma Proteins for Drug Delivery Applications. AB - BACKGROUND: Nanoparticulate delivery systems receive a lot of attention in pharmaceutical research and market due to their in vivo stability, ability to protect entrapped drug, and ease of cellular penetration. The hemocompatibility and the clearance half-life are important parameters of the nanodelivery systems that will be administered through intravenous route. Natural components, like blood plasma proteins are ideal sources of biomaterial for such systems with their long in vivo half-lives. METHODS: The aim of this work is to review in vitro, in vivo and clinical findings of nanocarriers based on blood plasma proteins, namely albumin, lipoproteins, fibrin/fibrinogen, transferrin. Plasma protein based nanocarriers loaded with different bioactive molecules (i.e., anti cancer, antiviral, anti-epileptic drugs, DNA) have been developed using different preparation methods like desolvation, emulsification, nab-technology, complexation methods. RESULTS: Human serum albumin has attracted the most attention in the last decade as nanocarrier due to its biocompatibility, high binding capacity to various drugs, and easy derivatization by covalent methods. Commercial products of albumin nanoparticles have emerged on the market after its recognition. Low and high density lipoproteins have recently been considered as valuable natural material for preparing hemocompatible small (app 20 nm) lipid protein vesicles. For other proteins of plasma, however, there are a limited number of studies that explored their potential as nanocarrier formulation. Therefore, there is huge research potential for investigating the proteins like globulins, fibrinogen and transferrin as part of nanocarrier core. CONCLUSION: Plasma protein based nanoparticulate delivery systems, especially albumin based ones have opened up and also will continue to open new treatment strategy options for treating cancer, AIDS and other complex life threatening diseases with advances in nanotechnology and science. PMID- 26861648 TI - Dextran-based Nanocarriers for Delivery of Bioactives. AB - BACKGROUND: Dextran (DX) is a natural polysaccharide produced in the laboratory by fermentation of sucrose under the effect of the enzyme DX sucrase (1,6-alpha-D glucan-alpha- glucosyltransferase). After harvesting and purification DX is subjected to cracking and separation to obtain the desired molecular weight. METHODS: The hydroxyl groups present in DX offer many sites for derivatization allowing the production of functionalized glycoconjugates biocompatible compound. DX and its derivatives are getting increased attention for use in core decoration or as carriers in novel drug delivery systems. This includes, among others, ion pairing, self-aggregate, protein and drug conjugates. DX carriers and camouflaged particles will be dealt with in this review to give emphasis on the great versatility of this natural biocompatible polysaccharide. CONCLUSION: With the continuous development in the area of drug delivery, we believe that the unique properties of this versatile nanocarrier platform will elect it as one of the cornerstones of safe nanodelivery systems. PMID- 26861649 TI - Advances on Magnetic Nanocarriers Based on Natural Polymers. AB - The use of nanodevices to transport active compounds like small-molecular drugs, peptides, or genes found an increased attention throughout the different fields of natural sciences. Moreover, recent research trends are focused on the employment of smart nanocarriers able to react on certain internal or external applied stimuli, in order to achieve temporal and site-specific drugs/gene release. In contrast to traditional biodegradable nanocarriers that slowly release drugs inside the cells, these smart nanosystems are able to quickly release or even dump drugs in response to a specific biological signal in the target cancer cells such lower pH, high redox potential or over expression of enzymes or to external stimuli such as temperature, light, ultrasounds and magnetic field. This review gives a brief overview about some types of stimuli responsive nanocarriers, with the main focus on magnetic fieldresponsive devices obtained from natural polymers. The concept of magnetic field-sensitive nanocarriers, their advantages and disadvantages, the methods of preparation and applications in various fields of drug delivery will be explored, giving an exhaustive collection of the findings of recent investigations. PMID- 26861650 TI - Mitochondrial Dysfunction and Endoplasmic Reticulum Stress in Diabetes. AB - It is generally accepted that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are related to insulin resistance and type 2 diabetes. Mitochondria use substrates from lipid and glucose metabolism in order to generate ATP, and when mitochondrial O2 consumption is decreased due to an altered metabolism there is an increase in reactive oxygen species (ROS) that can impair different types of molecules and cells, especially in beta- cells during type 2 diabetes. Furthermore, the maintenance of ER function in insulin-secreting beta-cells is crucial, and when ER homeostasis is disrupted, the ER develops an unfolded protein response (UPR) in order to maintain the homeostasis of this organelle. However, when homeostasis fails in mitochondria and ER, these organelles can initiate death signalling pathways. New research has suggested that hyperlipidemia and hyperliglucaemia, known as key factors of type 2 diabetes (T2D), disrupt mitochondrial activity and ER homeostasis, thus triggering a disruption of energy metabolism, unresolvable UPR activation and beta-cell death. This review explains the mechanisms of mitochondrial function and ER stress related to the pathological effects of type 2 diabetes in different tissues. PMID- 26861651 TI - Development of novel robust nanobiocatalyst for detergents formulations and the other applications of alkaline protease. AB - Alkaline protease from alkaliphilic Bacillus sp. NPST-AK15 was immobilized onto functionalized and non-functionalized rattle-type magnetic core@mesoporous shell silica (RT-MCMSS) nanoparticles by physical adsorption and covalent attachment. However, the covalent attachment approach was superior for NPST-AK15 protease immobilization onto the activated RT-MCMSS-NH2nanoparticles and was used for further studies. In comparison to free protease, the immobilized enzyme exhibited a shift in the optimal temperature and pH from 60 to 65 degrees C and pH 10.5 11.0, respectively. While free protease was completely inactivated after treatment for 1 h at 60 degrees C, the immobilized enzyme maintained 66.5% of its initial activity at similar conditions. The immobilized protease showed higher k cat and K m , than the soluble enzyme by about 1.3-, and 1.2-fold, respectively. In addition, the results revealed significant improvement of NPST AK15 protease stability in variety of organic solvents, surfactants, and commercial laundry detergents, upon immobilization onto activated RT-MCMSS NH2nanoparticles. Importantly, the immobilized protease maintained significant catalytic efficiency for ten consecutive reaction cycles, and was separated easily from the reaction mixture using an external magnetic field. To the best of our knowledge this is the first report about protease immobilization onto rattle type magnetic core@mesoporous shell silica nanoparticles that also defied activity-stability tradeoff. The results clearly suggest that the developed immobilized enzyme system is a promising nanobiocatalyst for various bioprocess applications requiring a protease. PMID- 26861652 TI - A novel neutral, halophile Stachybotrys microspora-based endoglucanase active impact on beta-glucan. AB - The production of cellulases from Stachybotrys microspora strain (A19) has been improved by fed-batch fermentation on Avicel cellulose 10 mg/ml. An endoglucanase EG2 was purified to homogeneity. This cellulase has a molecular mass estimated to 50 kDa when analyzed by a denaturant gel electrophoresis. It exhibited an optimal activity at 50 degrees C, pH 7.0 and 0.85 M NaCl. Specifically, these results show the thermo-active, alkali-tolerant and halo-tolerant properties of EG2. In addition, this endoglucanase showed its highest activity on barley-beta-glucan, compared to the CMC. Moreover, it was less active on Avicel cellulose. Furthermore, the EG2 activity was stimulated in the presence of EDTA, urea and beta-mercaptoethanol whereas it was reduced in the presence of SDS. This cellulase was highly stable in the presence of organic solvents such as acetone and n-hexane. TLC showed that the main hydrolysis products from EG2 were cellobiose and glucose. This fungal endoglucanase could be potentially important in the conversion of grass-derived biomass into fermentable sugars. PMID- 26861653 TI - The effect of simulated air conditions on N95 filtering facepiece respirators performance. AB - The objective of this study was to determine the effect of several simulated air environmental conditions on the particle penetration and the breathing resistance of two N95 filtering facepiece respirator (FFR) models. The particle penetration and breathing resistance of the respirators were evaluated in a test system developed to mimic inhalation and exhalation breathing while relative humidity and temperature were modified. Breathing resistance was measured over 120 min using a calibrated pressure transducer under four different temperature and relative humidity conditions without aerosol loading. Particle penetration was evaluated before and after the breathing resistance test at room conditions using a sodium chloride aerosol measured with a scanning mobility particle sizer. Results demonstrated that increasing relative humidity and lowering external temperature caused significant increases in breathing resistance (p < 0.001). However, these same conditions did not influence the penetration or most penetrating particle size of the tested FFRs. The increase in breathing resistance varied by FFR model suggesting that some FFR media are less influenced by high relative humidity. PMID- 26861654 TI - Relationship Between Buprenorphine Dosing and Triglyceride Lowering and Creatinine Kinase Elevation in Felines: Possible Human Implications. AB - Recently published feline data suggest that high doses of buprenorphine can elevate creatinine kinase (CK) and profoundly influence triglyceride levels in an inverted dose versus effect relationship. This intriguing observation in felines, hitherto not documented for buprenorphine, should be considered in human situations for any trends of translatability. The report evaluates the observed effects in domestic cats and what is known about buprenorphine in human subjects. Based on the objective assessment, the following are deduced: (a) although elevated CK levels is a nonissue in humans, one needs to pay attention especially when buprenorphine is used at the high end of therapeutic dose range in the presence of drugs that can impair the hepatic metabolism of buprenorphine; and (b) the potential for triglyceride lowering can be easily confirmed in human trials, and since it may occur at the relevant therapeutic doses of buprenorphine, it may be beneficial in such patients who may have added cardiovascular risk factors. PMID- 26861656 TI - Pathology of premalignant colorectal neoplasia. AB - Colorectal cancer is a heterogeneous oncological disease that develops through several molecular pathways. Each pathway is associated with specific neoplastic precursor lesions. Classification of colorectal polyps and the molecular features of associated colorectal cancers have undergone significant changes. An understanding of colorectal carcinogenesis and the molecular features of colorectal carcinomas is now regarded as necessary for personalized treatment and management of patients with colon cancer, and even for patients undergoing screening colonoscopy for early detection and prevention of colorectal cancer. In the present review, we describe the pathological and molecular features of epithelial precursor lesions involved in the early phases of colorectal carcinogenesis. PMID- 26861655 TI - On computerized methods for spine analysis in MRI: a systematic review. AB - PURPOSE: In the last decades, the increasing medical interest in magnetic resonance imaging (MRI) of the spine gave rise to a growing number of publications on computerized methods for spine analysis, covering goals such as localization and segmentation of vertebrae and intervertebral discs as well as the extraction and segmentation of the spinal canal and cord. We provide a critical systematic review to work in the field, putting focus on approaches that can be applied to different imaging sequences and settings. METHODS: Work is analysed on two levels. First, methods are reviewed in detail so that the reader understands justifications and constraints of particular work. Second, work is classified according to relevant attributes and tabulated to give an impression on recent trends. We discuss the general methodical and evaluational aspects of the work as well as challenges specific to MRI such as the lack of intensity standardization and partial volume effects. RESULTS: Methods can be condensed to a small number of optimization frameworks, e.g., graphical models, cost-minimal paths and deformable models. Works sharing the same framework mainly differentiate by the types of information, i.e., pose, geometry and appearance, that are used and by the implementation thereof. MRI-specific challenges are rarely addressed explicitly, calling into question the applicability of most methods to changing imaging sequences or settings. Most often, little attention is paid to evaluation, meaning that results lack comparability and reproducibility although publicly available data sets exist. CONCLUSION: The diversity of MRI sequences and settings still poses challenges to computerized spine analysis. Further research is necessary to implement methods that are actually applicable in practice, e.g., in clinical routine or for study purposes. Certainly, manual guidance will be necessary at some point, for instance to deal with changing subject positions. Therefore, future work should put attention to the appropriate integration of manual interaction. PMID- 26861657 TI - New Therapeutic Opportunities Based on DNA Mismatch Repair and BRAF Status in Metastatic Colorectal Cancer. AB - Recently, colorectal cancer (CRC) subtyping consortium identified four consensus molecular subtypes (CMS1-4). CMS1 is enriched for deficient mismatch repair (dMMR) and BRAF (V600E) tumors. Intriguingly, this subtype has better relapse free survival but worse overall survival after relapse compared with the other subtypes. Growing evidence is accumulating on the benefit of specific therapeutic strategies such as immune checkpoint inhibition therapy in dMMR tumors and mitogen-activated protein kinase (MAPK) pathway targeted therapy in tumors harboring BRAF (V600E) mutation. After reviewing dMMR prognostic value, immune checkpoints as major targets for dMMR carcinomas will be highlighted. Following, BRAF (V600E) prognostic impact will be reviewed and therapeutic strategies with the combination of cytotoxic agents and especially the combinations of BRAF and MAPK inhibitors will be discussed. PMID- 26861659 TI - ScaleNet: a literature-based model of scale insect biology and systematics. AB - Scale insects (Hemiptera: Coccoidea) are small herbivorous insects found on all continents except Antarctica. They are extremely invasive, and many species are serious agricultural pests. They are also emerging models for studies of the evolution of genetic systems, endosymbiosis and plant-insect interactions. ScaleNet was launched in 1995 to provide insect identifiers, pest managers, insect systematists, evolutionary biologists and ecologists efficient access to information about scale insect biological diversity. It provides comprehensive information on scale insects taken directly from the primary literature. Currently, it draws from 23,477 articles and describes the systematics and biology of 8194 valid species. For 20 years, ScaleNet ran on the same software platform. That platform is no longer viable. Here, we present a new, open-source implementation of ScaleNet. We have normalized the data model, begun the process of correcting invalid data, upgraded the user interface, and added online administrative tools. These improvements make ScaleNet easier to use and maintain and make the ScaleNet data more accurate and extendable. Database URL: http://scalenet.info. PMID- 26861658 TI - Acute kidney injury among ST elevation myocardial infarction patients treated by primary percutaneous coronary intervention: a multifactorial entity. AB - Acute kidney injury is a frequent complication among ST segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI), and is associated with adverse outcomes. While contrast nephropathy is considered the most important reason for worsening of renal function, recent data have suggested the role of other important factors among this specific patient population. In the present review, we examine the various factors leading to renal impairment in STEMI patients and place the findings in the context of this specific patient population in the era of primary PCI. These factors include contrast nephropathy, time to coronary reperfusion, cardiac pump function and hemodynamics as well as various inflammatory and metabolic markers. PMID- 26861660 TI - Value, but high costs in post-deposition data curation. AB - Discoverability of sequence data in primary data archives is proportional to the richness of contextual information associated with the data. Here, we describe an exercise in the improvement of contextual information surrounding sample records associated with metagenomics sequence reads available in the European Nucleotide Archive. We outline the annotation process and summarize findings of this effort aimed at increasing usability of publicly available environmental data. Furthermore, we emphasize the benefits of such an exercise and detail its costs. We conclude that such a third party annotation approach is expensive and has value as an element of curation, but should form only part of a more sustainable submitter-driven approach. Database URL: http://www.ebi.ac.uk/ena. PMID- 26861661 TI - Long-term mortality after stroke is higher than after myocardial infarction. AB - Mortality caused by coronary heart disease and ischemic stroke (IS) in Poland is still among the highest in Europe. Because acute myocardial infarction (AMI) and IS share major common risk factors, it would be expected that trends in long-term mortality (LTM) and incidence of these two diseases would be similar. Nevertheless, better AMI acute phase therapy and older age of IS patients make post-IS and post-AMI prognosis difficult to compare. The aim of the study was to verify the thesis that, regardless of age and sex, the long-term prognosis is worse for post-IS than for post-AMI subjects. The study was conducted in Polish city-Gdynia (250,000 of inhabitants) among 997 subjects (464 post-IS, 533 post AMI) randomly selected from all post-IS and post-AMI patients, witch survived hospitalization period in years 2000-2005. The observation period varied from 1 month to 11 years. LTM was shown as standardized mortality ratios. Kaplan-Meyer survival curves and Cox proportional hazard regression model were used to compare LTM in post-IS and post-AMI subjects. Post-IS and post-AMI groups did not differ by sex or age of event. Fewer deaths were recorded in post-AMI group (38.8 vs. 51.5 %, OR 0.60, 95 % CI 0.46-0.77). This difference was most evident in males (39.7 vs. 57.8 %, OR 0.48, 95 % CI 0.34-0.66). Kaplan-Meyer estimates showed faster reduction of survival probability in the post-IS males. In Cox regression model presence of IS increased long-term mortality in males. Long-term prognosis was worse for post-IS males in comparison with post-AMI population from Gdynia. PMID- 26861662 TI - Dispositional aspects of body focus and idiopathic environmental intolerance attributed to electromagnetic fields (IEI-EMF). AB - Body focus is often considered an undesirable characteristic from medical point of view as it amplifies symptoms and leads to higher levels of health anxiety. However, it is connected to mindfulness, well-being and the sense of self in psychotherapy. The current study aimed to investigate the contribution of various body focus related constructs to acute and chronic generation and maintenance of medically unexplained symptoms (MUS). Thirty-six individuals with idiopathic environmental intolerance to electromagnetic fields (IEI-EMF) and 36 controls were asked to complete questionnaires assessing negative affect, worries about harmful effects of EMFs, health anxiety (HA), body awareness, and somatosensory amplification (SSA), and to report experienced symptoms evoked by a sham magnetic field. Body awareness, HA, SSA, and EMF-related worries showed good discriminative power between individuals with IEI-EMF and controls. Considering all variables together, SSA was the best predictor of IEI-EMF. In the believed presence of a MF, people with IEI-EMF showed higher levels of anxiety and reported more symptoms than controls. In the IEI-EMF group, actual symptom reports were predicted by HA and state anxiety, while a reverse relationship between symptom reports and HA was found in the control group. Our findings show that SSA is a particularly important contributor to IEI-EMF, probably because it is the most comprehensive factor in its aetiology. IEI-EMF is associated with both a fear-related monitoring of bodily symptoms and a non-evaluative body focus. The identification of dispositional body focus may be relevant for the management of MUS. PMID- 26861663 TI - Effectiveness of braces designed using computer-aided design and manufacturing (CAD/CAM) and finite element simulation compared to CAD/CAM only for the conservative treatment of adolescent idiopathic scoliosis: a prospective randomized controlled trial. AB - PURPOSE: Clinical assessment of immediate in-brace effect of braces designed using CAD/CAM and FEM vs. only CAD/CAM for conservative treatment of AIS, using a randomized blinded and controlled study design. METHODS: Forty AIS patients were prospectively recruited and randomized into two groups. For 19 patients (control group), the brace was designed using a scan of patient's torso and a conventional CAD/CAM approach (CtrlBrace). For the 21 other patients (test group), the brace was additionally designed using finite element modeling (FEM) and 3D reconstructions of spine, rib cage and pelvis (NewBrace). The NewBrace design was simulated and iteratively optimized to maximize the correction and minimize the contact surface and material. RESULTS: Both groups had comparable age, sex, weight, height, curve type and severity. Scoliosis Research Society standardized criteria for bracing were followed. Average Cobb angle prior to bracing was 27 degrees and 28 degrees for main thoracic (MT) and lumbar (L) curves, respectively, for the control group, while it was 33 degrees and 28 degrees for the test group. CtrlBraces reduced MT and L curves by 8 degrees (29 %) and 10 degrees (40 %), respectively, compared to 14 degrees (43 %) and 13 degrees (46 %) for NewBraces, which were simulated with a difference inferior to 5 degrees . NewBraces were 50 % thinner and had 20 % less covering surface than CtrlBraces. CONCLUSION: Braces designed with CAD/CAM and 3D FEM simulation were more efficient and lighter than standard CAD/CAM TLSO's at first immediate in-brace evaluation. These results suggest that long-term effect of bracing in AIS may be improved using this new platform for brace fabrication. TRIAL REGISTRATION: NCT02285621. PMID- 26861664 TI - Variations in arterial supply to the lower lumbar spine. AB - PURPOSE: Several papers examined the vascular anatomy of the lumbosacral region using cadavers with angiography. However, few reports used CT angiography, and discussion on variations of fourth lumbar, fifth lumbar, and lumbar branch of iliolumbar arteries were limited. To clarify the vascular variations around the lower lumbar spine including the lumbosacral region, particularly at the posterior elements, we performed anatomical analysis using computed tomography (CT). METHODS: Extra-osseous arteries surrounding the lumbar spine including the lumbosacral region were evaluated by two orthopedic surgeons independently, using 323 consecutive abdominal contrast-enhanced multi-planner CT scans that were taken for surgical plans in colon cancer patients. Subjects were 204 men and 119 women, whose ages ranged from 15 to 89 years (mean 66.5). RESULTS: Each segmental artery was visible at the L1-4 spinal levels, running from the vertebra through the lamina in 91.0 % on the right side, in 90.7 % on the left side, while it was visible in 4.6 % on the right side, in 8.7 % on the left side at the L5 level. The extra-osseous arterial supply to the L5 lamina was basically provided by two vessels on each side. One was mostly derived from the L4 segmental artery (right: 92.6 %; left: 92.0 %) that was distributed around the superior articular process, the other was derived from the iliolumbar artery (right: 62.9 %; left: 55.7 %) that was distributed around the inferior articular process through the lamina. There were mainly four combination patterns of those arteries. These combinations, which had been considered as regular patterns in textbooks, were observed in approximately 50 % (right: 55.7 %; left: 48.6 %) of patients. CONCLUSION: Various distributions of arteries around the lower spine were identified. PMID- 26861665 TI - Robust method for TALEN-edited correction of pF508del in patient-specific induced pluripotent stem cells. AB - Cystic fibrosis is one of the most frequent inherited rare diseases, caused by mutations in the cystic fibrosis transmembrane conductance regulator gene. Apart from symptomatic treatments, therapeutic protocols for curing the disease have not yet been established. The regeneration of genetically corrected, disease-free epithelia in cystic fibrosis patients is envisioned by designing a stem cell/genetic therapy in which patient-derived pluripotent stem cells are genetically corrected, from which target tissues are derived. In this framework, we present an efficient method for seamless correction of pF508del mutation in patient-specific induced pluripotent stem cells by gene edited homologous recombination. Gene edition has been performed by transcription activator-like effector nucleases and a homologous recombination donor vector which contains a PiggyBac transposon-based double selectable marker cassette.This new method has been designed to partially avoid xenobiotics from the culture system, improve cell culture efficiency and genome stability by using a robust culture system method, and optimize timings. Overall, once the pluripotent cells have been amplified for the first nucleofection, the procedure can be completed in 69 days, and can be easily adapted to edit and change any gene of interest. PMID- 26861666 TI - Parecoxib Possesses Anxiolytic Properties in Patients Undergoing Total Knee Arthroplasty: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Clinical Study. AB - INTRODUCTION: Intravenous administration of parecoxib could provide significant pain relief in surgical operations that require additional forms of analgesia. However, very little is known about its effects on the anxiety levels of patients before a surgical procedure. The aim of this prospective study was to investigate whether intravenous parecoxib, pre-emptively administered, has an effect on anxiety levels experienced post-surgically after total knee arthroplasty (TKA) and if it influences the reported pain of the procedure itself. METHODS: A total of 90 patients who underwent TKA under spinal anesthesia were included in the study. Prior to TKA, all patients received continuous femoral nerve block (CFNB) and were randomized into two groups: Group D consisted of 45 patients who received the drug parecoxib intravenously in addition to CFNB, whereas Group P consisted of 45 patients who received a placebo drug (N/S 0.9 %) intravenously instead of parecoxib. All patients were asked to fill in the questionnaires STAI1 and STAI2 in order to evaluate anxiety levels pre- and post-surgically, respectively. One of the main aims was to distinguish personality-trait anxiety from state anxiety, i.e., anxiety experience due to the actual perioperative events and the actual pain endured. RESULTS: The group receiving parecoxib had statistically significant lower anxiety levels both for personality trait anxiety and state anxiety, as compared to the placebo group. CONCLUSIONS: Based on our findings, parecoxib had both analgesic and anxiolytic effects in patients undergoing TKA with CFNB. TRIAL REGISTRATION: Current Controlled Trials: NCT02185924. PMID- 26861667 TI - Sca-1(+) mesenchymal stromal cells inhibit splenic marginal zone B lymphocytes commitment through Caspase-3. AB - Mesenchymal stromal cells (MSCs) have been characterized as an important component of hematopoietic niche, which are capable of modulating the immune system through interaction with a wide range of immune cells. Marginal zone B cells, one main type of mature B lymphocytes, play a central role in eliciting antibody response against pathogens. However, how MSCs and its subpopulations regulate marginal zone B cells commitment is unknown yet. In this study, we assessed the contribution of Sca-1(+) MSCs on marginal zone B cells commitment. Our results showed that Sca-1(+) MSCs inhibit the commitment of marginal zone B lymphocytes. The inhibition was exerted through lowered Caspase-3 expression. Furthermore, we found marginal zone B lymphocytes in spleen of Caspase-3 knockout mice decreased and Caspase-3 knockout Sca-1(+) MSCs accounted for the MZB lymphocytes decrease. In conclusion, our investigation provided clues about Sca 1(+) MSCs regulation on the commitment of marginal zone B cells through Caspase-3 gene. PMID- 26861669 TI - Erratum. PMID- 26861668 TI - Endocytic pathways and endosomal trafficking: a primer. AB - This brief overview of endocytic trafficking is written in honor of Renate Fuchs, who retires this year. In the mid-1980s, Renate pioneered studies on the ion conducting properties of the recently discovered early and late endosomes and the mechanisms governing endosomal acidification. As described in this review, after uptake through one of many mechanistically distinct endocytic pathways, internalized proteins merge into a common early/sorting endosome. From there they again diverge along distinct sorting pathways, back to the cell surface, on to the trans-Golgi network or across polarized cells. Other transmembrane receptors are packaged into intraluminal vesicles of late endosomes/multivesicular bodies that eventually fuse with and deliver their content to lysosomes for degradation. Endosomal acidification, in part, determines sorting along this pathway. We describe other sorting machinery and mechanisms, as well as the rab proteins and phosphatidylinositol lipids that serve to dynamically define membrane compartments along the endocytic pathway. PMID- 26861671 TI - Evaluation of Multiple Blood Matrices for Assessment of Human Exposure to Nerve Agents. AB - Biomedical samples may be used to determine human exposure to nerve agents through the analysis of specific biomarkers. Samples received may include serum, plasma, whole blood, lysed blood and, due to the toxicity of these compounds, postmortem blood. To quantitate metabolites resulting from exposure to sarin (GB), soman (GD), cyclosarin (GF), VX and VR, these blood matrices were evaluated individually for precision, accuracy, sensitivity and specificity. Accuracies for these metabolites ranged from 100 to 113% with coefficients of variation ranging from 2.31 to 13.5% across a reportable range of 1-100 ng/mL meeting FDA recommended guidelines for bioanalytical methods in all five matrices. Limits of detection were calculated to be 0.09-0.043 ng/mL, and no interferences were detected in unexposed matrix samples. The use of serum calibrators was also determined to be a suitable alternative to matrix-matched calibrators. Finally, to provide a comparative value between whole blood and plasma, the ratio of the five nerve agent metabolites measured in whole blood versus plasma was determined. Analysis of individual whole blood samples (n = 40), fortified with nerve agent metabolites across the reportable range, resulted in average nerve agent metabolite blood to plasma ratios ranging from 0.53 to 0.56. This study demonstrates the accurate and precise quantitation of nerve agent metabolites in serum, plasma, whole blood, lysed blood and postmortem blood. It also provides a comparative value between whole blood and plasma samples, which can assist epidemiologists and physicians with interpretation of test results from blood specimens obtained under variable conditions. PMID- 26861672 TI - GIRD, TRROM, and humeral torsion-based classification of shoulder risk in throwing athletes are not in agreement and should not be used interchangeably. AB - OBJECTIVES: Clinicians commonly interpret the findings of shoulder rotational ranges of motion using various approaches: an apparent reduction in dominant arm internal rotation ("GIRD"), a difference in total rotational range of motion-i.e. differences in the sum of internal and external rotational range (TRROM), and a combination of rotational ROM and torsional difference ("GIRD-torsion"). We have noticed that these approaches are being considered to provide equivalent estimates of shoulder rotational range. This investigation sought to document the extent of agreement of these three different approaches when classifying athletes' "at-risk" status. DESIGN: Observational cohort study. METHODS: 162 professional male athletes participating in overhead sports (baseball, handball, and volleyball) had their GIRD, TRROM, and GIRD-torsion calculated, and classified as "at risk" using standard cut-points of 20 degrees , 5 degrees , and 10 degrees , respectively. RESULTS: 25 (15.4%) athletes were classified as "at risk" using GIRD, 55 (34%) with TRROM, and 30 (18.5%) using GIRD-torsion. Only 3/162 (1.9%) athletes were classified as "at-risk" by all 3 approaches, 4 athletes were concurrently classified as "at-risk" by GIRD and TRROM (Kappa= 0.142, poor agreement), 11 by GIRD and GIRD-torsion (Kappa=0.279, fair agreement), and 11 by TRROM and GIRD-torsion (Kappa=0.025, slight agreement). RESULTS: 25 (15.4%) athletes were classified as at risk using GIRD, 55 (34%) with TRROM, and 30 (18.5%) using GIRD-torsion. Only 3/162 (1.9%) athletes were classified as at risk by all 3 approaches, 4 athletes were concurrently classified as at risk by GIRD and TRROM (Kappa=-0.142, poor agreement), 11 by GIRD and GIRD-torsion (Kappa=0.279, fair agreement), and 11 by TRROM and GIRD torsion (Kappa=0.025, slight agreement). CONCLUSIONS: The three described approaches yield demonstrably different findings, and these approaches cannot be used interchangeably. Examples of clinical reasoning are provided to assist with the interpretation of these different measures. PMID- 26861670 TI - Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity. AB - Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients, predominantly with DC matured with pro-inflammatory cytokines and prostaglandin E2. We studied the safety and efficacy of vaccination with monocyte-derived DC matured with a cocktail of prophylactic vaccines that contain clinical-grade Toll like receptor ligands (BCG, Typhim, Act-HIB) and prostaglandin E2 (VAC-DC). Stage III and IV melanoma patients were vaccinated via intranodal injection (12 patients) or combined intradermal/intravenous injection (16 patients) with VAC-DC loaded with keyhole limpet hemocyanin (KLH) and mRNA encoding tumor antigens gp100 and tyrosinase. Tumor antigen-specific T cell responses were monitored in blood and skin-test infiltrating-lymphocyte cultures. Almost all patients mounted prophylactic vaccine- or KLH-specific immune responses. Both after intranodal injection and after intradermal/intravenous injection, tumor antigen-specific immune responses were detected, which coincide with longer overall survival in stage IV melanoma patients. VAC-DC induce local and systemic CTC grade 2 and 3 toxicity, which is most likely caused by BCG in the maturation cocktail. The side effects were self-limiting or resolved upon a short period of systemic steroid therapy. We conclude that VAC-DC can induce functional tumor-specific responses. Unfortunately, toxicity observed after vaccination precludes the general application of VAC-DC, since in DC maturated with prophylactic vaccines BCG appears to be essential in the maturation cocktail. PMID- 26861673 TI - Advances in Synthetic Applications of Hypervalent Iodine Compounds. AB - The preparation, structure, and chemistry of hypervalent iodine compounds are reviewed with emphasis on their synthetic application. Compounds of iodine possess reactivity similar to that of transition metals, but have the advantage of environmental sustainability and efficient utilization of natural resources. These compounds are widely used in organic synthesis as selective oxidants and environmentally friendly reagents. Synthetic uses of hypervalent iodine reagents in halogenation reactions, various oxidations, rearrangements, aminations, C-C bond-forming reactions, and transition metal-catalyzed reactions are summarized and discussed. Recent discovery of hypervalent catalytic systems and recyclable reagents, and the development of new enantioselective reactions using chiral hypervalent iodine compounds represent a particularly important achievement in the field of hypervalent iodine chemistry. One of the goals of this Review is to attract the attention of the scientific community as to the benefits of using hypervalent iodine compounds as an environmentally sustainable alternative to heavy metals. PMID- 26861674 TI - Sleep apnea, hypertension, and hemorrhagic stroke-deja vu all over again. PMID- 26861675 TI - D-Serine in the nucleus accumbens region modulates behavioral sensitization and extinction of conditioned place preference. AB - BACKGROUND: D-serine, the endogenous co-agonist of N-methyl-D-aspartate receptors (NMDARs), is considered to be essential for learning and memory. The aim of the current investigation was to systematically evaluate the role of D-serine on addiction behaviors considered to be mediated by the nucleus accumbens (NAc). METHODS: D-Serine concentration in the NAc was measured by high-performance liquid chromatography (HPLC). Cocaine-induced behavioral sensitization and conditioned place preference (CPP) models were used to evaluate the relation between changes in serine in the nucleus accumbens and cocaine-induced behavioral effects. The expression of serine racemase (SR), D-amino acid oxidase (DAAO), the cAMP response element-binding protein (CREB) and upstream kinases, and N-methyl-D aspartate (NMDA) receptors subunits were analyzed by western blot. Long-term depression (LTD) in the NAc was investigated by electrophysiological methods. RESULTS: The NAc slices obtained from the behavioral sensitization rats presented significantly reduced D-serine concentrations, increased expression of DAAO, and down-regulated expression of SR in a dose-dependent manner. Furthermore, D-serine injections into the nucleus accumbens blocked the development of behavioral sensitization and caused extinction of CPP. The ERK-CREB-Fos pathway and the NMDA receptor NR2B subunits in the NAc were involved in the cocaine-induced behavioral sensitization. We also found that D-serine was essential for NMDAR-dependent LTD and D-serine-regulated LTD in a bell-shaped concentration-dependent manner. The disrupted NMDAR-dependent LTD in the NAc of cocaine-treated rats was reversed by D-serine. CONCLUSIONS: Our results provide evidence for a critical role of D serine in synaptic plasticity relevant to cocaine addiction and indicate that D serine may be an effective therapeutic agent for cocaine addiction. PMID- 26861676 TI - Role Models and Teachers: medical students perception of teaching-learning methods in clinical settings, a qualitative study from Sri Lanka. AB - BACKGROUND: Medical education research in general, and those focusing on clinical settings in particular, have been a low priority in South Asia. This explorative study from 3 medical schools in Sri Lanka, a South Asian country, describes undergraduate medical students' experiences during their final year clinical training with the aim of understanding the teaching-learning experiences. METHODS: Using qualitative methods we conducted an exploratory study. Twenty eight graduates from 3 medical schools participated in individual interviews. Interview recordings were transcribed verbatim and analyzed using qualitative content analysis method. RESULTS: Emergent themes reveled 2 types of teaching learning experiences, role modeling, and purposive teaching. In role modelling, students were expected to observe teachers while they conduct their clinical work, however, this method failed to create positive learning experiences. The clinical teachers who predominantly used this method appeared to be 'figurative' role models and were not perceived as modelling professional behaviors. In contrast, purposeful teaching allowed dedicated time for teacher-student interactions and teachers who created these learning experiences were more likely to be seen as 'true' role models. Students' responses and reciprocations to these interactions were influenced by their perception of teachers' behaviors, attitudes, and the type of teaching-learning situations created for them. CONCLUSIONS: Making a distinction between role modeling and purposeful teaching is important for students in clinical training settings. Clinical teachers' awareness of their own manifest professional characterizes, attitudes, and behaviors, could help create better teaching-learning experiences. Moreover, broader systemic reforms are needed to address the prevailing culture of teaching by humiliation and subordination. PMID- 26861677 TI - Medicago truncatula Gaertn. as a model for understanding the mechanism of growth promotion by bacteria from rhizosphere and nodules of alfalfa. AB - MAIN CONCLUSION: The present study showed all the 16 strains isolated and identified from the alfalfa rhizosphere and nodules, and registered in GenBank, to be good candidates for targeted use in studies addressing the rather weak known mechanism of plant growth promotion, including that of Medicago truncatula, a molecular crop model. Based on physiological, biochemical and molecular analysis, the 16 isolates obtained were ascribed to the following five families: Bacillaceae, Rhizobiaceae, Xantomonadaceae, Enterobacteriaceae and Pseudomonadaceae, within which 9 genera and 16 species were identified. All these bacteria were found to significantly enhance fresh and dry weight of root, shoots and whole 5-week-old seedlings. The bacteria were capable of the in vitro use of tryptophan to produce indolic compounds at various concentrations. The ability of almost all the strains to enhance growth of seedlings and individual roots was positively correlated with the production of the indolic compounds (r = 0.69; P = 0.0001), but not with the 1-aminocyclopropane-1-carboxylate deaminase (ACCD) activity (no correlation). For some strains, it was difficult to conclude whether the growth promotion was related to the production of indolic compounds or to the ACCD activity. It is likely that promotion of M. truncatula root development involves also root interaction with pseudomonads, known to produce 2,4 diacetylphloroglucinol (DAPG), a secondary metabolite reported to alter the root architecture by interacting with an auxin-dependent signaling pathway. Inoculation of seedlings with Pseudomonas brassicacearum KK 5, a bacterium known for its lowest ability to produce indolic compounds, the highest ACCD activity and the presence of the phlD gene responsible for DAPG precursor synthesis, resulted in a substantial promotion of root development. Inoculation with the strain increased the endogenous IAA level in M. truncatula leaves after inoculation of 5-week-old seedlings. Three other strains examined in this study also increased the IAA level in the leaves upon inoculation. Moreover, several other factors such as mobilization of phosphorus and zinc to make them available to plants, iron sequestration by siderophore production and the ability to ammonia production also contributed substantially to the phytostimulatory biofertilizing potential of isolated strains. There is, thus, evidence that Medicago truncatula growth promotion by rhizobacteria involves more than one mechanism. PMID- 26861680 TI - 3D Printing of Graphene Aerogels. AB - 3D printing of a graphene aerogel with true 3D overhang structures is highlighted. The aerogel is fabricated by combining drop-on-demand 3D printing and freeze casting. The water-based GO ink is ejected and freeze-cast into designed 3D structures. The lightweight (<10 mg cm(-3) ) 3D printed graphene aerogel presents superelastic and high electrical conduction. PMID- 26861679 TI - Suhuang antitussive capsule at lower doses attenuates airway hyperresponsiveness, inflammation, and remodeling in a murine model of chronic asthma. AB - Suhuang antitussive capsule (Suhuang), a traditional Chinese medication, is found effective in treating chronic cough and cough variant asthma (CVA). This study aimed to determine the possible effects and underlying mechanisms of Suhuang on chronic ovalbumin (OVA)-induced airway hyperresponsiveness (AHR), inflammation, and remodeling in mice. Mice were randomly assigned to six experimental groups: control, OVA model with or without Suhuang (low dose: 3.5 g/kg, middle dose: 7.0 g/kg, high dose: 14.0 g/kg), or dexamethasone (2.5 mg/kg). AHR, inflammatory cells, cytokines in bronchoalveolar lavage fluid (BALF), lung pathology, mucus production, and airway remodeling were examined. We found Suhuang treated at lower doses effectively inhibited OVA-induced AHR, airway inflammation, mucus production and collagen deposition around the airway. High dose of Suhuang reduced most of the inflammatory hallmarks while exerted inconsiderable effects on the number of macrophages in BALF and AHR. At all doses, Suhuang significantly reduced the levels of interlukin (IL) -13 and transforming growth factor (TGF) beta1, but had little effects on IL-4, IL-5, IL-17A and interferon (IFN)-gamma. Thus, Suhuang administration alleviates the pathological changes of chronic asthma likely through inhibition of IL-13 and TGF-beta1. Suhuang might be a promising therapy for patients with allergic asthma in the future. PMID- 26861678 TI - Nanoparticle-Mediated Targeting of Cyclosporine A Enhances Cardioprotection Against Ischemia-Reperfusion Injury Through Inhibition of Mitochondrial Permeability Transition Pore Opening. AB - Myocardial ischemia-reperfusion (IR) injury limits the therapeutic effects of early reperfusion therapy for acute myocardial infarction (MI), in which mitochondrial permeability transition pore (mPTP) opening plays a critical role. Our aim was to determine whether poly-lactic/glycolic acid (PLGA) nanoparticle mediated mitochondrial targeting of a molecule that inhibits mPTP opening, cyclosporine A (CsA), enhances CsA-induced cardioprotection. In an in vivo murine IR model, intravenously injected PLGA nanoparticles were located at the IR myocardium mitochondria. Treatment with nanoparticles incorporated with CsA (CsA NP) at the onset of reperfusion enhanced cardioprotection against IR injury by CsA alone (as indicated by the reduced MI size at a lower CsA concentration) through the inhibition of mPTP opening. Left ventricular remodeling was ameliorated 28 days after IR, but the treatment did not affect inflammatory monocyte recruitment to the IR heart. In cultured rat cardiomyocytes in vitro, mitochondrial PLGA nanoparticle-targeting was observed after the addition of hydrogen peroxide, which represents oxidative stress during IR, and was prevented by CsA. CsA-NP can be developed as an effective mPTP opening inhibitor and may protect organs from IR injury. PMID- 26861681 TI - Deterministic error correction for nonlocal spatial-polarization hyperentanglement. AB - Hyperentanglement is an effective quantum source for quantum communication network due to its high capacity, low loss rate, and its unusual character in teleportation of quantum particle fully. Here we present a deterministic error correction scheme for nonlocal spatial-polarization hyperentangled photon pairs over collective-noise channels. In our scheme, the spatial-polarization hyperentanglement is first encoded into a spatial-defined time-bin entanglement with identical polarization before it is transmitted over collective-noise channels, which leads to the error rejection of the spatial entanglement during the transmission. The polarization noise affecting the polarization entanglement can be corrected with a proper one-step decoding procedure. The two parties in quantum communication can, in principle, obtain a nonlocal maximally entangled spatial-polarization hyperentanglement in a deterministic way, which makes our protocol more convenient than others in long-distance quantum communication. PMID- 26861682 TI - Maternal-foetal transfer of Plasmodium falciparum and Plasmodium vivax antibodies in a low transmission setting. AB - During pregnancy immunoglobulin G (IgG) antibodies are transferred from mother to neonate across the placenta. Studies in high transmission areas have shown transfer of P. falciparum-specific IgG, but the extent and factors influencing maternal-foetal transfer in low transmission areas co-endemic for both P. falciparum and P. vivax are unknown. Pregnant women were screened weekly for Plasmodium infection. Mother-neonate paired serum samples at delivery were tested for IgG to antigens from P. falciparum, P. vivax and other infectious diseases. Antibodies to malarial and non-malarial antigens were highly correlated between maternal and neonatal samples (median [range] spearman rho = 0.78 [0.57-0.93]), although Plasmodium spp. antibodies tended to be lower in neonates than mothers. Estimated gestational age at last P. falciparum infection, but not P. vivax infection, was positively associated with antibody levels in the neonate (P. falciparum merozoite, spearman rho median [range] 0.42 [0.33-0.66], PfVAR2CSA 0.69; P. vivax rho = 0.19 [0.09-0.3]). Maternal-foetal transfer of anti-malarial IgG to Plasmodium spp. antigens occurs in low transmission settings. P. vivax IgG acquisition is not associated with recent exposure unlike P. falciparum IgG, suggesting a difference in acquisition of antibodies. IgG transfer is greatest in the final weeks of pregnancy which has implications for the timing of future malaria vaccination strategies in pregnant women. PMID- 26861683 TI - The effect of glenosphere size on functional outcome for reverse shoulder arthroplasty. AB - PURPOSE: Reverse shoulder arthroplasty (RSA) is an effective surgery for a variety of patients with difficult shoulder pathology. Since postsurgical outcomes are often variable, there has been great effort made to optimize the design and use of these implants. Previous studies demonstrated an association between increased glenosphere size and improved range of motion. The purpose of this study is to assess the relationship between glenosphere size, range of motion, and functional outcome scores. METHODS: This is a retrospective cohort study of 140 patients (148 shoulders) undergoing reverse shoulder arthroplasty. All patients were assessed pre- and postoperatively for range of motion, Constant score, ASES score, and Subjective Shoulder Value. Improvements in these variables were compared for patients treated with three different glenosphere sizes (36, 40, 42 mm). RESULTS: All groups had a mean improvement in range of motion and functional outcome scores, but there were no statistically significant differences between groups when controlling for preoperative differences. CONCLUSIONS: Our findings do not support a strong role for glenosphere size as a singular factor affecting range of motion or patient-reported outcome following RSA. These problems are most likely due to the multifactorial nature of shoulder dynamics. For this reason, assessing the effect a single surgical or biomechanical parameter on function has been challenging. PMID- 26861684 TI - Atomically isolated nickel species anchored on graphitized carbon for efficient hydrogen evolution electrocatalysis. AB - Hydrogen production through electrochemical process is at the heart of key renewable energy technologies including water splitting and hydrogen fuel cells. Despite tremendous efforts, exploring cheap, efficient and durable electrocatalysts for hydrogen evolution still remains as a great challenge. Here we synthesize a nickel-carbon-based catalyst, from carbonization of metal-organic frameworks, to replace currently best-known platinum-based materials for electrocatalytic hydrogen evolution. This nickel-carbon-based catalyst can be activated to obtain isolated nickel atoms on the graphitic carbon support when applying electrochemical potential, exhibiting highly efficient hydrogen evolution performance with high exchange current density of 1.2 mA cm(-2) and impressive durability. This work may enable new opportunities for designing and tuning properties of electrocatalysts at atomic scale for large-scale water electrolysis. PMID- 26861685 TI - The impact of combined interpretation of localization studies on image-guided surgical approaches for primary hyperparathyroidism. AB - BACKGROUND: The impact of single and combined interpretations of ultrasonography and sestamibi scintigraphy to select the appropriate surgical approach in patients with primary hyperparathyroidism were evaluated retrospectively. METHODS: A total of 183 patients with primary hyperparathyroidism who were evaluated preoperatively using both ultrasonography and sestamibi scintigraphy were included in the study. The results of preoperative localization studies were correlated with intraoperative findings and postoperative histopathological results. The localization rates of individual and combined interpretations of ultrasonography and sestamibi scintigraphy were evaluated. RESULTS: The overall sensitivity and the positive predictive value of ultrasonography and sestamibi scintigraphy were 76% and 90%, and 81% and 91%, respectively. Both imaging studies were concordant for the same localization(s) in 121 (66%) of 183 patients. The prevalence rates of single-gland and multiglandular disease were 90% (N.=109) and 10% (N.=12), respectively, in patients with concordant results (P=0.0001). The overall rate of localization was 91% (N.=110) in these patients. In these patients with concordant results, the sensitivity and the positive predictive value of imaging were 91% and 100%, respectively. The localization rates were 96% and 42% for single-gland and multiglandular disease, respectively (P=0.0001). Of the remaining 62 patients, 50 had negative imaging with either ultrasonography (N.=29) or MIBI (N.=21). Of the 29 patients with negative ultrasonography results, sestamibi scintigraphy was positive in 23. Of the 21 patients with negative sestamibi scintigraphy imaging, ultrasonography was positive in 15. Thus, 38 patients had a single positive imaging result. The majority (95%) of these 38 patients had single-gland disease, and the rate of multiglandular disease was 5% (P=0.0001). The rate of localization was 95% (36/38) in patients with a single positive imaging study. Eighteen patients had discordant imaging results. CONCLUSIONS: The overall rate of localization in primary hyperparathyroidism is greater than 90% if ultrasonography and sestamibi scintigraphy are concordantly positive for the same localization, and the prevalence of multiglandular disease is low in patients with concordant imaging. An image-guided surgical approach and selective parathyroidectomy exhibit high cure rates in the setting of concordantly positive sestamibi and ultrasonography results, even if intraoperative parathormone monitoring is not used. PMID- 26861686 TI - Experimental realization of the Yang-Baxter Equation via NMR interferometry. AB - The Yang-Baxter equation is an important tool in theoretical physics, with many applications in different domains that span from condensed matter to string theory. Recently, the interest on the equation has increased due to its connection to quantum information processing. It has been shown that the Yang Baxter equation is closely related to quantum entanglement and quantum computation. Therefore, owing to the broad relevance of this equation, besides theoretical studies, it also became significant to pursue its experimental implementation. Here, we show an experimental realization of the Yang-Baxter equation and verify its validity through a Nuclear Magnetic Resonance (NMR) interferometric setup. Our experiment was performed on a liquid state Iodotrifluoroethylene sample which contains molecules with three qubits. We use Controlled-transfer gates that allow us to build a pseudo-pure state from which we are able to apply a quantum information protocol that implements the Yang Baxter equation. PMID- 26861687 TI - DT(270-326) , a Truncated Diphtheria Toxin, Increases Blood-Tumor Barrier Permeability by Upregulating the Expression of Caveolin-1. AB - AIM: The nontoxic mutant of diphtheria toxin (DT) has been demonstrated to act as a receptor-specific carrier protein to delivery drug into brain. Recent research showed that the truncated "receptorless" DT was still capable of being internalized into cells. This study investigated the effects and potential mechanisms of DT(270-326) , a truncated "receptorless" DT, on the permeability of the blood-tumor barrier (BTB). METHODS: BTB and GECs were subjected to DT(270 326) treatment. HRP flux assays, immunofluorescent, co-immunoprecipitation, Western blot, CCK-8, and Flow cytometry analysis were used to evaluate the effects of DT(270-326) administration. RESULTS: Our results revealed that 5 MUM of DT(270-326) significantly increased the permeability of BTBin vitro, which reached its peak at 6 h. The permeability was reduced by pretreatment with filipinIII. DT(270-326) co-localized and interacted with caveolin-1 via its caveolin-binding motif. The mRNA and protein expression levels of caveolin-1 were identical with the changes of BTB permeability. The upregulated expression of caveolin-1 was associated with Src kinase-dependent tyrosine phosphorylation of caveolin-1, which subsequently induced phosphorylation and inactivation of the transcription factor Egr-1. The combination of DT(270-326) with doxorubicin significantly enhanced the loss of cell viability and apoptosis of U87 glioma cells in contrast to doxorubicin alone. CONCLUSIONS: DT(270-326) might provide a novel strategy to increase the delivery of macromolecular therapeutic agents across the BTB. PMID- 26861688 TI - Mesostructured silica and aluminosilicate carriers for oxytetracycline delivery systems. AB - Oxytetracycline delivery systems containing various MCM-type silica and aluminosilicate with different antibiotic content were developed in order to establish the influence of the support structural and textural properties and aluminum content on the drug release profile. The antibiotic molecules were loaded into the support mesochannels by incipient wetness impregnation method using a drug concentrated aqueous solution. The carriers and drug-loaded materials were investigated by small- and wide-angle XRD, FTIR spectroscopy, TEM and N2 adsorption-desorption isotherms. Faster release kinetics of oxytetracycline from uncalcined silica and aluminosilicate supports was observed, whereas higher drug content led to lower delivery rate. The presence of aluminum into the silica network also slowed down the release rate. The antimicrobial assays performed on Staphylococcus aureus clinical isolates showed that the oxytetracycline-loaded materials containing MCM-41-type mesoporous silica or aluminosilicate carriers inhibited the bacterial development. PMID- 26861689 TI - Enhanced oral bioavailability and in vivo antioxidant activity of chlorogenic acid via liposomal formulation. AB - In the present study, a formulation system consisting of cholesterol and phosphatidyl choline was used to prepare an effective chlorogenic acid-loaded liposome (CAL) with an improved oral bioavailability and an increased antioxidant activity. The developed liposomal formulation produced regular, spherical and multilamellar-shaped distribution nanoparticles. The pharmacokinetic analysis of CAL compared with chlorogenic acid (CA), showed a higher value of Cmax(6.42 +/- 1.49 min versus 3.97 +/- 0.39 min) and a delayed Tmax(15 min versus 10 min), with 1.29-fold increase in relative oral bioavailability. The tissue distribution in mice also demonstrated that CAL predominantly accumulated in the liver which indicated hepatic targeting potential of the drug. The increased activities of antioxidant enzymes (Total Superoxide Dismutase (T-SOD) and Glutathione Peroxidase (GSH-Px)) and total antioxidant capacity (T-AOC), in addition to decreased level of malondialdehyde (MDA) in CCl4-induced hepatotoxicity study further revealed that CAL exhibited significant hepatoprotective and antioxidant effects. Collectively, these findings present a liposomal formulation with significantly improved oral bioavailability and an increased in vivo antioxidant activity of CA. PMID- 26861690 TI - Nonlinear transcriptomic response to dietary fat intake in the small intestine of C57BL/6J mice. AB - BACKGROUND: A high caloric diet, in conjunction with low levels of physical activity, promotes obesity. Many studies are available regarding the relation between dietary saturated fats and the etiology of obesity, but most focus on liver, muscle and white adipose tissue. Furthermore, the majority of transcriptomic studies seek to identify linear effects of an external stimulus on gene expression, although such an assumption does not necessarily hold. Our work assesses the dose-dependent effects of dietary fat intake on differential gene expression in the proximal, middle and distal sections of the small intestine in C57BL/6J mice. Gene expression is analyzed in terms of either linear or nonlinear responses to fat intake. RESULTS: The highest number of differentially expressed genes was observed in the middle section. In all intestine sections, most of the identified processes exhibited a linear response to increasing fat intake. The relative importance of logarithmic and exponential responses was higher in the proximal and distal sections, respectively. Functional enrichment analysis highlighted a constantly linear regulation of acute-phase response along the whole small intestine, with up-regulation of Serpina1b. The study of gene expression showed that exponential down-regulation of cholesterol transport in the middle section is coupled with logarithmic up-regulation of cholesterol homeostasis. A shift from linear to exponential response was observed in genes involved in the negative regulation of caspase activity, from middle to distal section (e.g., Birc5, up-regulated). CONCLUSIONS: The transcriptomic signature associated with inflammatory processes preserved a linear response in the whole small intestine (e.g., up-regulation of Serpina1b). Processes related to cholesterol homeostasis were particularly active in the middle small intestine and only the highest fat intake down-regulated cholesterol transport and efflux (with a key role played by the down-regulation of ATP binding cassette transporters). Characterization of nonlinear patterns of gene expression triggered by different levels of dietary fat is an absolute novelty in intestinal studies. This approach helps identifying which processes are overloaded (i.e., positive, logarithmic regulation) or arrested (i.e., negative, exponential regulation) in response to excessive fat intake, and can shed light on the relationships linking lipid intake to obesity and its associated molecular disturbances. PMID- 26861692 TI - Three-dimensional free-standing carbon nanotubes for a flexible lithium-ion battery anode. AB - Flexible lithium-ion batteries (LIBs) have received considerable attention as energy sources for wearable electronics. In recent years, much effort has been devoted to study light-weight, robust, and flexible electrodes. However, high areal and volumetric capacities need to be achieved for practical power and energy densities. In this paper, we report the use of three-dimensional (3D) free standing carbon nanotubes (CNTs) as a current collector-free anode to demonstrate flexible LIBs with enhanced areal and volumetric capacities. High density CNTs grown on copper (Cu) mesh are transferred to a flexible graphene/polyethylene terephthalate film and integrated into a flexible LIB. A fully flexible LIB cell integrated with the 3D CNT anode delivers a high areal capacity of 0.25 mAh cm( 2) at 0.1C and shows fairly consistent open circuit voltage under bending. These findings may provide significant advances in the application of flexible LIB based electronic devices. PMID- 26861691 TI - A guide to human in vivo microcirculatory flow image analysis. AB - Various noninvasive microscopic camera technologies have been used to visualize the sublingual microcirculation in patients. We describe a comprehensive approach to bedside in vivo sublingual microcirculation video image capture and analysis techniques in the human clinical setting. We present a user perspective and guide suitable for clinical researchers and developers interested in the capture and analysis of sublingual microcirculatory flow videos. We review basic differences in the cameras, optics, light sources, operation, and digital image capture. We describe common techniques for image acquisition and discuss aspects of video data management, including data transfer, metadata, and database design and utilization to facilitate the image analysis pipeline. We outline image analysis techniques and reporting including video preprocessing and image quality evaluation. Finally, we propose a framework for future directions in the field of microcirculatory flow videomicroscopy acquisition and analysis. Although automated scoring systems have not been sufficiently robust for widespread clinical or research use to date, we discuss promising innovations that are driving new development. PMID- 26861693 TI - Walking ability to predict future cognitive decline in old adults: A scoping review. AB - Early identification of individuals at risk for cognitive decline may facilitate the selection of those who benefit most from interventions. Current models predicting cognitive decline include neuropsychological and/or biological markers. Additional markers based on walking ability might improve accuracy and specificity of these models because motor and cognitive functions share neuroanatomical structures and psychological processes. We reviewed the relationship between walking ability at one point of (mid) life and cognitive decline at follow-up. A systematic literature search identified 20 longitudinal studies. The average follow-up time was 4.5 years. Gait speed quantified walking ability in most studies (n=18). Additional gait measures (n=4) were step frequency, variability and step-length. Despite methodological weaknesses, results revealed that gait slowing (0.68-1.1 m/sec) preceded cognitive decline and the presence of dementia syndromes (maximal odds and hazard ratios of 10.4 and 11.1, respectively). The results indicate that measures of walking ability could serve as additional markers to predict cognitive decline. However, gait speed alone might lack specificity. We recommend gait analysis, including dynamic gait parameters, in clinical evaluations of patients with suspected cognitive decline. Future studies should focus on examining the specificity and accuracy of various gait characteristics to predict future cognitive decline. PMID- 26861694 TI - Human islets and dendritic cells generate post-translationally modified islet autoantigens. AB - The initiation of type 1 diabetes (T1D) requires a break in peripheral tolerance. New insights into neoepitope formation indicate that post-translational modification of islet autoantigens, for example via deamidation, may be an important component of disease initiation or exacerbation. Indeed, deamidation of islet autoantigens increases their binding affinity to the T1D highest-risk human leucocyte antigen (HLA) haplotypes HLA-DR3/DQ2 and -DR4/DQ8, increasing the chance that T cells reactive to deamidated autoantigens can be activated upon T cell receptor ligation. Here we investigated human pancreatic islets and inflammatory and tolerogenic human dendritic cells (DC and tolDC) as potential sources of deamidated islet autoantigens and examined whether deamidation is altered in an inflammatory environment. Islets, DC and tolDC contained tissue transglutaminase, the key enzyme responsible for peptide deamidation, and enzyme activity increased following an inflammatory insult. Islets treated with inflammatory cytokines were found to contain deamidated insulin C-peptide. DC, heterozygous for the T1D highest-risk DQ2/8, pulsed with native islet autoantigens could present naturally processed deamidated neoepitopes. HLA-DQ2 or -DQ8 homozygous DC did not present deamidated islet peptides. This study identifies both human islets and DC as sources of deamidated islet autoantigens and implicates inflammatory activation of tissue transglutaminase as a potential mechanism for islet and DC deamidation. PMID- 26861695 TI - Barriers and enablers to integrating maternal and child health services to antenatal care in low and middle income countries. AB - Antenatal care (ANC) represents a delivery platform for a broad range of health services; however, these opportunities are insufficiently utilised. This review explores key barriers and enablers for successful integration of health s"ervices with ANC in different contexts. Data from peer-reviewed and grey literature were organised using the SURE checklist. We identified 46 reports focusing on integration of HIV, tuberculosis, malaria, syphilis or nutrition services with ANC from Asia, Africa and the Pacific. Perspectives of service users and providers, social and political factors, and health system characteristics (such as resource availability and organisational structures) affected ease of integration. TWEETABLE ABSTRACT: Health system factors, context and stakeholders must be considered for integrated antenatal care services. PMID- 26861696 TI - High recurrence rate supports need for secondary prophylaxis in non-HIV patients with disseminated mycobacterium avium complex infection: a multi-center observational study. AB - BACKGROUND: Long-term outcomes in non-HIV immunocompromised patients with disseminated Mycobacterium avium complex (dMAC) infections are unknown and the need for post-treatment secondary prophylaxis against MAC is uncertain in this setting. The objective of this study was to determine the need of continuing secondary anti-MAC prophylaxis in non-HIV patients after completing treatment of the primary dMAC episode. METHODS: We conducted a ten-year multi-center analysis of non-HIV immunosuppressed patients with dMAC infections in Hong Kong. RESULTS: We observed sixteen patients with dMAC during the study period of which five (31 %) were non-HIV immunosuppressed patients. In the non-HIV immunosuppressed group, three patients completed a treatment course without secondary prophylaxis, one patient received azithromycin-based secondary prophylaxis and one patient was still receiving therapy for the first dMAC episode. All the three patients who completed treatment without being given secondary prophylaxis developed recurrent dMAC infection requiring retreatment. CONCLUSIONS: In view of the high rate of dMAC infection recurrence in non-HIV immunocompromised patients following treatment completion, our data support long-term anti-MAC suppression therapy after treatment of the first dMAC infection episode in immunocompromised non-HIV patients, as is recommended for patients with advanced HIV. Tests of cell mediated immune function need to be evaluated to guide prophylaxis discontinuation in non-HIV patients. PMID- 26861697 TI - Validation of conversion between mini-mental state examination and montreal cognitive assessment. AB - INTRODUCTION: Harmonizing data across cohorts is important for validating findings or combining data in meta-analyses. We replicate and validate a previous conversion of MoCA to MMSE in PD. METHODS: We used five studies with 1,161 PD individuals and 2,091 observations measured with both the MoCA and MMSE. We compared a previously published conversion table using equipercentile equating with log-linear smoothing to our internally derived scores. RESULTS: Both conversions found good agreement within and across the studies when comparing true and converted MMSE (mean difference: 0.05; standard deviation: 1.84; median difference: 0; interquartile range: -1 to 1, using internal conversion). CONCLUSIONS: These results show that one can get a reliable and valid conversion between two commonly used measures of cognition in PD studies. These approaches need to be applied to other scales and domains to enable large-scale collaborative analyses across multiple PD cohorts. PMID- 26861700 TI - Could the inhalation of cadmium and other metals in addition to textile dust inhalation account for the observed increased risk of rheumatoid arthritis in textile workers? PMID- 26861699 TI - Recombinant pharmaceuticals from microbial cells: a 2015 update. AB - Diabetes, growth or clotting disorders are among the spectrum of human diseases related to protein absence or malfunction. Since these pathologies cannot be yet regularly treated by gene therapy, the administration of functional proteins produced ex vivo is required. As both protein extraction from natural producers and chemical synthesis undergo inherent constraints that limit regular large scale production, recombinant DNA technologies have rapidly become a choice for therapeutic protein production. The spectrum of organisms exploited as recombinant cell factories has expanded from the early predominating Escherichia coli to alternative bacteria, yeasts, insect cells and especially mammalian cells, which benefit from metabolic and protein processing pathways similar to those in human cells. Up to date, around 650 protein drugs have been worldwide approved, among which about 400 are obtained by recombinant technologies. Other 1300 recombinant pharmaceuticals are under development, with a clear tendency towards engineered versions with improved performance and new functionalities regarding the conventional, plain protein species. This trend is exemplified by the examination of the contemporary protein-based drugs developed for cancer treatment. PMID- 26861698 TI - Suppression of RAF/MEK or PI3K synergizes cytotoxicity of receptor tyrosine kinase inhibitors in glioma tumor-initiating cells. AB - BACKGROUND: The majority of glioblastomas have aberrant receptor tyrosine kinase (RTK)/RAS/phosphoinositide 3 kinase (PI3K) signaling pathways and malignant glioma cells are thought to be addicted to these signaling pathways for their survival and proliferation. However, recent studies suggest that monotherapies or inappropriate combination therapies using the molecular targeted drugs have limited efficacy possibly because of tumor heterogeneities, signaling redundancy and crosstalk in intracellular signaling network, indicating necessity of rationale and methods for efficient personalized combination treatments. Here, we evaluated the growth of colonies obtained from glioma tumor-initiating cells (GICs) derived from glioma sphere culture (GSC) in agarose and examined the effects of combination treatments on GICs using targeted drugs that affect the signaling pathways to which most glioma cells are addicted. METHODS: Human GICs were cultured in agarose and treated with inhibitors of RTKs, non-receptor kinases or transcription factors. The colony number and volume were analyzed using a colony counter, and Chou-Talalay combination indices were evaluated. Autophagy and apoptosis were also analyzed. Phosphorylation of proteins was evaluated by reverse phase protein array and immunoblotting. RESULTS: Increases of colony number and volume in agarose correlated with the Gompertz function. GICs showed diverse drug sensitivity, but inhibitions of RTK and RAF/MEK or PI3K by combinations such as EGFR inhibitor and MEK inhibitor, sorafenib and U0126, erlotinib and BKM120, and EGFR inhibitor and sorafenib showed synergy in different subtypes of GICs. Combination of erlotinib and sorafenib, synergistic in GSC11, induced apoptosis and autophagic cell death associated with suppressed Akt and ERK signaling pathways and decreased nuclear PKM2 and beta-catenin in vitro, and tended to improve survival of nude mice bearing GSC11 brain tumor. Reverse phase protein array analysis of the synergistic treatment indicated involvement of not only MEK and PI3K signaling pathways but also others associated with glucose metabolism, fatty acid metabolism, gene transcription, histone methylation, iron transport, stress response, cell cycle, and apoptosis. CONCLUSION: Inhibiting RTK and RAF/MEK or PI3K could induce synergistic cytotoxicity but personalization is necessary. Examining colonies in agarose initiated by GICs from each patient may be useful for drug sensitivity testing in personalized cancer therapy. PMID- 26861701 TI - Separately tackling the development of erosions with denosumab: ultimately closing a gap in the treatment of patients with rheumatoid arthritis or trying too hard too late? PMID- 26861702 TI - The Tuscan Mobile Simulation Program: a description of a program for the delivery of in situ simulation training. AB - Simulation has become a critical aspect of medical education. It allows health care providers the opportunity to focus on safety and high-risk situations in a protected environment. Recently, in situ simulation, which is performed in the actual clinical setting, has been used to recreate a more realistic work environment. This form of simulation allows for better team evaluation as the workers are in their traditional roles, and can reveal latent safety errors that often are not seen in typical simulation scenarios. We discuss the creation and implementation of a mobile in situ simulation program in emergency departments of three hospitals in Tuscany, Italy, including equipment, staffing, and start-up costs for this program. We also describe latent safety threats identified in the pilot in situ simulations. This novel approach has the potential to both reduce the costs of simulation compared to traditional simulation centers, and to expand medical simulation experiences to providers and healthcare organizations that do not have access to a large simulation center. PMID- 26861704 TI - Different site, different clinical outcomes in perforated colorectal cancer? PMID- 26861703 TI - Epidemiology of diabetes and complications among adults in the Republic of Ireland 1998-2015: a systematic review and meta-analysis. AB - BACKGROUND: Accurate estimates of the burden of diabetes are essential for future planning and evaluation of services. In Ireland, there is no diabetes register and prevalence estimates vary. The aim of this review was to systematically identify and review studies reporting the prevalence of diabetes and complications among adults in Ireland between 1998 and 2015 and to examine trends in prevalence over time. METHODS: A systematic literature search was carried out using PubMed and Embase. Diabetes prevalence estimates were pooled by random effects meta-analysis. Poisson regression was carried out using data from four nationally representative studies to calculate prevalence rates of doctor diagnosed diabetes between 1998 and 2015 and was also used to assess whether the rate of doctor diagnosed diabetes changed over time. RESULTS: Fifteen studies (eight diabetes prevalence and seven complication prevalence) were eligible for inclusion. In adults aged 18 years and over, the national prevalence of doctor diagnosed diabetes significantly increased from 2.2 % in 1998 to 5.2 % in 2015 (p trend <= 0.001). The prevalence of diabetes complications ranged widely depending on study population and methodology used (6.5-25.2 % retinopathy; 3.2-32.0 % neuropathy; 2.5-5.2 % nephropathy). CONCLUSIONS: Between 1998 and 2015, there was a significant increase in the prevalence of doctor diagnosed diabetes among adults in Ireland. Trends in microvascular and macrovascular complications prevalence could not be examined due to heterogeneity between studies and the limited availability of data. Reliable baseline data are needed to monitor improvements in care over time at a national level. A comprehensive national diabetes register is urgently needed in Ireland. PMID- 26861705 TI - Transanal endoscopic microsurgery is an oncologically safe alternative to total mesorectal excision for stage I rectal cancer: results of a meta-analysis of randomized controlled trials. PMID- 26861706 TI - Throw a bone here: an evil and rare consequence of foreign body passage. PMID- 26861708 TI - Kinetic Analysis of Membrane Potential Dye Response to NaV1.7 Channel Activation Identifies Antagonists with Pharmacological Selectivity against NaV1.5. AB - The NaV1.7 voltage-gated sodium channel is a highly valued target for the treatment of neuropathic pain due to its expression in pain-sensing neurons and human genetic mutations in the gene encoding NaV1.7, resulting in either loss-of function (e.g., congenital analgesia) or gain-of-function (e.g., paroxysmal extreme pain disorder) pain phenotypes. We exploited existing technologies in a novel manner to identify selective antagonists of NaV1.7. A full-deck high throughput screen was developed for both NaV1.7 and cardiac NaV1.5 channels using a cell-based membrane potential dye FLIPR assay. In assay development, known local anesthetic site inhibitors produced a decrease in maximal response; however, a subset of compounds exhibited a concentration-dependent delay in the onset of the response with little change in the peak of the response at any concentration. Therefore, two methods of analysis were employed for the screen: one to measure peak response and another to measure area under the curve, which would capture the delay-to-onset phenotype. Although a number of compounds were identified by a selective reduction in peak response in NaV1.7 relative to 1.5, the AUC measurement and a subsequent refinement of this measurement were able to differentiate compounds with NaV1.7 pharmacological selectivity over NaV1.5 as confirmed in electrophysiology. PMID- 26861707 TI - Factors associated with the location of local rectal cancer recurrence and predictors of survival. AB - PURPOSE: The location of locally recurrent rectal cancer (LRRC) may influence survival. This study examines factors affecting the location of LRRC, the effect of LRRC location on survival, and predictive factors for survival in patients with LRRC. METHODS: Patients undergoing initial proctectomy and subsequent management of LRRC at the Cleveland Clinic (1980-2011) were included. Data regarding index surgery, LRRC, and survival were obtained from a prospectively maintained database. RESULTS: One hundred and fifty-seven patients were identified with a mean follow-up 59.8 +/- 50.1 months and time to LRRC of 31.7 +/ 30.1 months. Sixty patients underwent surgery with curative intent. Anastomotic leak and retrieving less than 12 lymph nodes at index proctectomy were associated with posterior (P = 0.019) and lateral (P = 0.036) recurrences, respectively. Having an axial relative to an anterior, posterior, or lateral recurrence was associated with improved overall survival (P = 0.001). On multivariable analysis, undergoing primarily palliative treatment (OR, 5.2; 95 % confidence interval (CI), 3.2-8.4; P < 0.001), age at LRRC >60 years (OR, 1.9; 95 % CI, 1.3-2.7, P < 0.001), advanced primary tumour stage (OR, 1.5; 95 % CI, 1.1-2.1; P = 0.021), and anastomotic leak at index surgery (OR, 1.8; 95 % CI, 1.2-2.7; P = 0.008) were associated with reduced LRRC 5-year survival. CONCLUSIONS: The current study suggests that features of the primary tumour and technical factors at the time of index proctectomy influence both the location of LRRC and survival. PMID- 26861709 TI - Loneliness and Ethnic Composition of the School Class: A Nationally Random Sample of Adolescents. AB - Loneliness is a public health concern that increases the risk for several health, behavioral and academic problems among adolescents. Some studies have suggested that adolescents with an ethnic minority background have a higher risk for loneliness than adolescents from the majority population. The increasing numbers of migrant youth around the world mean growing numbers of heterogeneous school environments in many countries. Even though adolescents spend a substantial amount of time at school, there is currently very little non-U.S. research that has examined the importance of the ethnic composition of school classes for loneliness in adolescence. The present research aimed to address this gap by exploring the association between loneliness and three dimensions of the ethnic composition in the school class: (1) membership of ethnic majority in the school class, (2) the size of own ethnic group in the school class, and (3) the ethnic diversity of the school class. We used data from the Danish 2014 Health Behaviour in School-aged Children survey: a nationally representative sample of 4383 (51.2 % girls) 11-15-year-olds. Multilevel logistic regression analyses revealed that adolescents who did not belong to the ethnic majority in the school class had increased odds for loneliness compared to adolescents that belonged to the ethnic majority. Furthermore, having more same-ethnic classmates lowered the odds for loneliness. We did not find any statistically significant association between the ethnic diversity of the school classes and loneliness. The study adds novel and important findings to how ethnicity in a school class context, as opposed to ethnicity per se, influences adolescents' loneliness. PMID- 26861711 TI - Deadlock persists over junior doctor contract. PMID- 26861710 TI - Perceived Ethnic Discrimination by Teachers and Ethnic Minority Students' Academic Futility: Can Parents Prepare Their Youth for Better or for Worse? AB - This study focuses on the interplay of perceived ethnic discrimination by teachers, parents' ethnic socialization practices, and ethnic minority students' sense of academic futility. Since discrimination creates barriers beyond control of the individual, the first research goal is to examine the association of perceived ethnic discrimination by teachers with ethnic minority students' sense of academic futility. The second research goal is to focus on the role of perceived parental ethnic socialization (e.g., cultural socialization and preparation for bias) to get a better understanding of the interaction between family level factors and the potentially negative consequences of ethnic teacher discrimination. A multilevel analysis on 1181 ethnic minority students (50.6 % girls; mean age = 15.5), originating from migration, in 53 secondary schools in Flanders (Belgium) shows that the frequent perception of ethnic discrimination by teachers is associated with stronger feelings of academic futility, and if these students also received high levels of parents' ethnic socialization, they perceive even stronger feelings of futility. The group of ethnic minority students, who perceive frequent ethnic teacher discrimination, is a group at risk, and parents' ethnic socialization does not seem able to change this. PMID- 26861712 TI - Downregulation of let-7b promotes COL1A1 and COL1A2 expression in dermis and skin fibroblasts during heat wound repair. AB - MicroRNAs (miRs), a class of non-coding RNAs 18-25 nucleotides in length, generally serve suppressive role in the regulation of gene expression via directly binding to the 3'-untranslated region (UTR) of their target mRNA. Previous studies have identified several miRs to be involved in thermal injury repair. However, the role of miR let-7b during the recovery of thermal injury, in addition to the underlying mechanisms, has not previously been studied. In the present study, the expression of let-7b was observed to be significantly increased in skin tissue shortly following thermal injury, however, gradually reduced during the recovery of thermal injury. Notably, similar findings were observed in heat-denatured skin fibroblasts. Furthermore, collagen, type I, alpha 1 (COL1A1) and collagen, type I, alpha 2 (COL1A2), which are associated with the synthesis of type I collagen, were identified as two targets of let-7b in skin fibroblasts. The overexpression of let-7b was observed to upregulate the protein expression levels of COL1A1 and COL1A2, while knockdown of let-7b reduced the levels of COL1A1 and COL1A2 in skin fibroblasts. Furthermore, COL1A1 and COL1A2 were significantly downregulated shortly following thermal injury, while gradually upregulated during healing, in heat-damaged skin tissue and skin fibroblasts, with the expression profiles opposite to that of let-7b. Taken together, this suggests that the downregulation of let-7b in heat-damaged dermis promotes the synthesis of type I collagen and thus aids in burn wound repair. PMID- 26861713 TI - Psychiatric Co-occurring Symptoms and Disorders in Young, Middle-Aged, and Older Adults with Autism Spectrum Disorder. AB - Although psychiatric problems are less prevalent in old age within the general population, it is largely unknown whether this extends to individuals with autism spectrum disorders (ASD). We examined psychiatric symptoms and disorders in young, middle-aged, and older adults with and without ASD (Nmax = 344, age 19-79 years, IQ > 80). Albeit comparable to other psychiatric patients, levels of symptoms and psychological distress were high over the adult lifespan; 79 % met criteria for a psychiatric disorder at least once in their lives. Depression and anxiety were most common. However, older adults less often met criteria for any psychiatric diagnosis and, specifically, social phobia than younger adults. Hence, despite marked psychological distress, psychiatric problems are also less prevalent in older aged individuals with ASD. PMID- 26861714 TI - Experiences of Autism Spectrum Disorder and Policing in England and Wales: Surveying Police and the Autism Community. AB - An online survey gathered the experiences and views of 394 police officers (from England and Wales) regarding autism spectrum disorder (ASD). Just 42 % of officers were satisfied with how they had worked with individuals with ASD and reasons for this varied. Although officers acknowledged the need for adjustments, organisational/time constraints were cited as barriers. Whilst 37 % of officers had received training on ASD, a need for training tailored to policing roles (e.g., frontline officers, detectives) was identified. Police responses are discussed with respect to the experiences of the ASD community (31 adults with ASD, 49 parents), who were largely dissatisfied with their experience of the police and echoed the need for police training on ASD. PMID- 26861715 TI - Seeing the Forest and the Trees: Default Local Processing in Individuals with High Autistic Traits Does Not Come at the Expense of Global Attention. AB - Atypical sensory perception is one of the most ubiquitous symptoms of autism, including a tendency towards a local-processing bias. We investigated whether local-processing biases were associated with global-processing impairments on a global/local attentional-scope paradigm in conjunction with a composite-face task. Behavioural results were related to individuals' levels of autistic traits, specifically the Attention to Detail subscale of the Autism Quotient, and the Sensory Profile Questionnaire. Individuals showing high rates of Attention to Detail were more susceptible to global attentional-scope manipulations, suggesting that local-processing biases associated with Attention to Detail do not come at the cost of a global-processing deficit, but reflect a difference in default global versus local bias. This relationship operated at the attentional/perceptual level, but not response criterion. PMID- 26861716 TI - Autism Spectrum Disorder in the DSM-5: Diagnostic Sensitivity and Specificity in Early Childhood. AB - Changes to the DSM-5 Autism Spectrum Disorder (ASD) criteria raised concerns among parents and practitioners that the criteria may exclude some children with Pervasive Developmental Disorder (PDD). Few studies have examined DSM-5 sensitivity and specificity in children less than 5 years of age. This study evaluated 185 children aged 20-55 months with DSM-IV PDD or developmental delay. Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) data was assigned to DSM-5 subdomains. Children displaying the required symptomatology were classified with DSM-5 ASD. DSM-IV clinical diagnoses were compared to DSM-5 classifications. Using combined ADI-R/ADOS information, sensitivity was .84 and specificity was .54. Comorbid behaviour and emotional problems were significantly lower in children with PDD that did not meet DSM-5 criteria. PMID- 26861717 TI - Change in the Behavioral Phenotype of Adolescents and Adults with FXS: Role of the Family Environment. AB - The present study examined trajectories of adaptive behavior, behavior problems, psychological symptoms, and autism symptoms in adolescents and adults with fragile X syndrome (n = 147) over a three-year period. Adaptive behavior significantly increased over time, particularly for adolescents, and the severity of behavior problems decreased over time. Family environmental factors predicted phenotypic variables net of gender, intellectual disability status, and medication use. Maternal warmth was associated with higher levels of adaptive behavior, lower levels of autism symptoms, and decreases in behavior problems over time. Maternal depressive symptoms and criticism were associated with higher levels of psychological symptoms. Implications for interventions are discussed. PMID- 26861719 TI - Brief Report: An Observational Measure of Empathy for Autism Spectrum: A Preliminary Study of the Development and Reliability of the Client Emotional Processing Scale. AB - People with autism spectrum disorder (ASD), can have difficulties in emotion processing, including recognising their own and others' emotions, leading to problems in emotion regulation and interpersonal relating. This study reports the development and piloting of the Client Emotional Processing Scale-Autism Spectrum (CEPS-AS), a new observer measure of four interrelated aspects of emotional processing: emotion recognition, self-reflection, cognitive empathy, and affective empathy. Results showed good interrater reliability (alpha: .69-.91), while inter-dimension associations were high (r = .66-.82). The measure was able to detect significant differences on the four dimensions across a short-term humanistic-experiential group therapy. The CEPS-AS shows promise as a potential addition to current self-report instruments measuring empathy or emotion processes in individuals with ASD. PMID- 26861720 TI - Social Tools And Rules for Teens (The START Program): Program Description and Preliminary Outcomes of an Experiential Socialization Intervention for Adolescents with Autism Spectrum Disorder. AB - Experiential learning is an essential process in the development of core social competencies. Unfortunately, adolescents with autism spectrum disorders often do not possess the prerequisite skillset and motivation to sustain the level of social immersion needed to benefit from this learning process. These persisting social vulnerabilities can limit their long-term relational success and associated quality of life, creating a need for comprehensive social programming. This paper describes a multi-component socialization intervention that simultaneously targets motivational, conceptual, and skill deficits using a hybrid experiential/didactic treatment approach. Evidence of social competence improvements was noted in survey and live conversational measures, indicating that the START program may hold promise as a method for improving the social success of participating adolescents with ASD. PMID- 26861718 TI - Three-Dimensional Kinematic Analysis of Prehension Movements in Young Children with Autism Spectrum Disorder: New Insights on Motor Impairment. AB - The study was aimed at better clarifying whether action execution impairment in autism depends mainly on disruptions either in feedforward mechanisms or in feedback-based control processes supporting motor execution. To this purpose, we analyzed prehension movement kinematics in 4- and 5-year-old children with autism and in peers with typical development. Statistical analysis showed that the kinematics of the grasp component was spared in autism, whereas early kinematics of the reach component was atypical. We discussed this evidence as suggesting impairment in the feedforward processes involved in action execution, whereas impairment in feedback-based control processes remained unclear. We proposed that certain motor abilities are available in autism, and children may use them differently as a function of motor context complexity. PMID- 26861721 TI - Vulvar mucinous adenocarcinoma with neuroendocrine differentiation: A case report and review of the literature. AB - BACKGROUND: There are limited cases in literature of patients with mucinous adenocarcinoma of the vulva with neuroendocrine differentiation have. With this new case, we aim to provide an overview of the existing literature and present a tool with relevant markers for the pathologist in the differential diagnosis. CASE DESCRIPTION: A 92-year-old multiparous, Caucasian woman presented with a 8 cm spherical tumor of the left major labium. Since the initial punch biopsy was not conclusive, a local resection was performed. Histopathological examination showed mucus production, large pools of mucin with trabeculae and cribriform glandular structures with strongly atypical columnar epithelium. Additional immunohistochemical analysis demonstrated expression of: CEA, CK7, EMA, and the neuroendocrine markers synaptophysin and chromogranin supporting the diagnosis. CONCLUSION: In this report, we present a new case of a mucinous adenocarcinoma of the vulva with neuroendocrine differentiation based immunohistochemical analysis. Due to the indolent tumor behavior, partial vulvectomy is the therapy of choice. PMID- 26861722 TI - Placental findings associated with maternal obesity at early pregnancy. AB - INTRODUCTION: Obesity during pregnancy is associated with a wide spectrum of maternal, fetal and neonatal complications. This study compared placental pathology in women with obesity and normal weight gravidas. MATERIALS AND METHODS: This is a retrospective case-control study. The sample was randomly selected from a total of 1000 deliveries of largely Caucasian population in a single institution, recruited for the study of sleep disordered breathing, where the placenta is submitted for pathological examination for clinical indications based on national guidelines. Cases (Body mass index - BMI >= 30 kg/m(2); n = 47) and controls (BMI < 25 kg/m(2), n = 45) were selected based on BMI obtained from the first prenatal visit. Placental pathology, clinical parameters and limited outcomes were extracted from medical records. Placental weight range was defined as small for gestational age (SGA) if < 10th percentile, large for gestational age (LGA) if > 90th percentile. RESULTS: Mean BMI was 36.2 +/- 5.5 in the group with obesity and 21.7 +/- 1.9 in the control group (p < 0.01). There was a significantly higher prevalence of diabetes in cases compared to controls (14/47 vs. 3/45, p = 0.006) while preterm birth was significantly higher in the control group (9/47 vs. 19/46, p = 0.02). There were more LGA placentas in cases versus controls (12/47 vs. 2/46, p = 0.007; even after adjusting for diabetes). More histological features of inflammation, marginal insertion of the umbilical cord and intervillous thrombi in the parenchyma were also noted in the case group. CONCLUSIONS: Results from the current study suggest that maternal obesity measured at early pregnancy may have effects on both placental implantation and growth, and further exacerbate the hypercoagulable state in placenta. PMID- 26861723 TI - Xanthine Oxidase Pathway and Muscle Damage. Insights from McArdle Disease. AB - The intent of this article is to summarize current body of knowledge on the potential implication of the xanthine oxidase pathway (XO) on skeletal muscle damage. The possible involvement of the XO pathway in muscle damage is exemplified by the role of XO inhibitors (e.g., allopurinol) in attenuating muscle damage. Reliance on this pathway (as well as on the purine nucleotide cycle) could be exacerbated in conditions of low muscle glycogen availability. Thus, we also summarize current hypotheses on the etiology of both baseline and exertional muscle damage in McArdle disease, a condition caused by inherited deficiency of myophosphorylase. Because myophosphorylase catalyzes the first step of muscle glycogen breakdown, patients are unable to obtain energy from their muscle glycogen stores. Finally, we provide preliminary data from our laboratory on the potential implication of the XO pathway in the muscle damage that is commonly experienced by these patients. PMID- 26861724 TI - MicroRNA-208a Potentiates Angiotensin II-triggered Cardiac Myoblasts Apoptosis via Inhibiting Nemo-like Kinase (NLK). AB - INTRODUCTION: MicroRNA-208a (miR-208a) exacerbated cardiomyocyte apoptosis via inhibiting nemo-like kinase (NLK). miR-208a is a crucial molecule in the regulation of heart diseases, however, the biological function and underlying mechanism of miR-208a in the progression of cardiomyocyte apoptosis is not clearly elucidated. We hypothesized that miR-208a might potentiate cardiomyocyte apoptosis through inhibiting NLK. METHODS: Male Sprague-Dawley rats were underwent permanent coronary artery ligation to establish myocardial infarction (MI) model. The quantitative real-time RT-PCR (qRT-PCR) was used to evaluate the expression of miR-208a and NLK mRNA. Western blot was applied to detect NLK and Bcl-2 proteins expression. Luciferase reporter assay was performed to indentify NLK as a target of miR-208a. The apoptosis of H9C2 cells was assessed by flow cytometry (FCM). RESULTS: miR-208a was upregulated accompanying with a significant decrease of NLK in response to MI, and stronger miR-208a staining was detected by in situ hybridization in the cytoplasm of cardiomyocytes in MI group compared to the sham group. In vitro, overexpression of miR-208a greatly enhance Ang II-induced the apoptosis of H9C2 cells through downregulating of NLK and the anti-apoptosis protein Bcl-2 expression, whereas these effects were reversed when miR-208a was downregulated. Dual luciferase reporter assay and western blot results demonstrated that NLK was a direct target of miR-208a. Interestingly, upregulation of NLK obviously increased Bcl-2 expression and reduced the percentage of apoptotic cells, while attenuation of NLK reduced the level of Bcl 2 and cells apoptosis after treatment with Ang II. CONCLUSIONS: miR-208a can promote Ang II-induced cardiomyocyte apoptosis via negatively regulating NLK expression, and inhibition of miR-208a may provide a novel therapeutic target for cardiomyocyte apoptosis. PMID- 26861725 TI - Inhaled Biologics: From Preclinical to Product Approval. AB - BACKGROUND: Delivery of pharmacologically active compounds to the lung for systemic effects is well known and recently has entered a new era with several products achieving regulatory approval. This review focuses on the barriers to pulmonary delivery of biologics. METHODS: Lessons learned from the development of recently approved products will be reviewed to shed light on the current challenges that are faced when developing biological products for inhaled delivery. RESULTS: The text and tables presented herein consolidate the current data and ongoing research regarding biological, inhaled products. CONCLUSION: With this basis, we also review the future prospects for pulmonary delivery of biologics for systemic delivery and how the biological and physical barriers may be overcome. PMID- 26861726 TI - An efficient closed-form design method for nearly perfect reconstruction of non uniform filter bank. AB - In this paper, an efficient closed form method for the design of multi-channel nearly perfect reconstruction of non-uniform filter bank with the prescribed stopband attenuation and channel overlapping is presented. In this method, the design problem of multi-channel non-uniform filter bank (NUFB) is considered as the design of a prototype filter whose magnitude response at quadrature frequency is 0.707, which is exploited for finding the optimum passband edge frequency through empirical formula instead of using single or multivariable optimization technique. Two main attributes used in assessing the performance of filter bank are peak reconstruction error (PRE) and computational time (CPU time). As compared to existing methods, this method is very simple and easy to implement for NUFBs. To implement this algorithm, a Matlab program has been developed, and several examples are presented to illustrate the performance of proposed method. PMID- 26861727 TI - Analysis of association between common variants in the SLCO6A1 gene with schizophrenia, bipolar disorder and major depressive disorder in the Han Chinese population. AB - OBJECTIVES: The SLCO6A1 gene belongs to a superfamily of genes which is known to be a solute carrier family of OATPs (SLCO). The SLCO6A1 gene encodes OATP6A1 protein in humans. A previous genome-wide association study (GWAS) of schizophrenia conducted in the Swedish population demonstrated a significant association of rs6878284, which is located in the SLCO6A1 gene, with schizophrenia. To further investigate whether this gene is also a risk locus for schizophrenia (SCZ), bipolar disorder (BPD) and major depressive disorder (MDD) in the Han Chinese population, a case-control study was designed. METHODS: In total 1,248 unrelated SCZ cases, 1,344 BPD cases, 1,056 unrelated MDD cases and 1,248 normal controls were analysed in this study. We genotyped five SNPs using the Sequenom MassARRAY platform. RESULTS: We found no association of rs6878284 with SCZ [Corrected Pallele = 0.969, Corrected Pgenotype = 0.997]. Furthermore, we found a statistically significant association of the rs7734060 genotype with MDD after correction [rs7734060: Corrected Pallele = 0.114, Corrected Pgenotype = 0.036] in the Han Chinese population. CONCLUSIONS: This is the first study which reveals no association of rs6878284 with SCZ and also predicts that rs7734060 could be a risk locus for MDD in the Han Chinese population. PMID- 26861728 TI - Disseminated nodules after vaccines for hyposensitization for mites. Pseudolymphoma or lymphoma? PMID- 26861729 TI - A comparison of engineering controls for formaldehyde exposure during grossing activities in health care anatomic pathology laboratories. AB - This article for the first time reports a large set of monitoring results for formaldehyde exposure during grossing activities in health care anatomic pathology laboratories, and compares the effectiveness of different local exhaust ventilation systems on the exposure. To control the confounding effects from grossing work load, sampling duration, and the sizes of specimens grossed, only 15-min short-term personal exposure samples collected during large tissue specimen grossing were used for the comparison of the effectiveness of these local exhaust systems. While we also collected long-term 8-hr time weighted average samples, these are not treated in this analysis. The systems examined were canopy receiving hoods, slot exhausts, and commercially available pre manufactured backdraft grossing stations, both recirculating and ducted exhaust types. Out of over 2,000 personal short-term air samples, 307 samples from 163 surveys met the data selection criteria. Over a third of the data were less than the analytical laboratory limits of detection. Using the robust maximum likelihood estimation method for multiple limits of detection, the mean and geometric mean of the dataset for each type of local exhaust system were found to be less than the short-term personal exposure regulatory limit of 2 ppm. Nonparametric Wilcoxon rank-sum pairwise tests of five types of engineering controls showed a statistically significant difference among these controls, with the most effective being the manufactured backdraft grossing stations ducted to the outside, and the least effective being canopy exhaust systems and manufactured filtered recirculating grossing stations. Finally, exposure with each of the major engineering control types was rated by the American Industrial Hygiene Association exposure control rating scheme. PMID- 26861730 TI - Clinical and radiological outcomes of lumbar posterior subtraction osteotomies are correlated to pelvic incidence and FBI index : Prospective series of 63 cases. AB - PURPOSE: Pedicle subtraction osteotomy (PSO) is one of the surgical options for treating alignment disorders of the fused spine (due to post-surgical fusion or related to arthritis). It enables satisfactory sagittal realignment and improved function due to economic sagittal balance. The aim of this study was to analyze clinical and radiological results of PSO after a minimum follow-up of 2 years and demonstrate the benefit of sub-group analysis as a function of pelvic incidence (PI). METHODS: A descriptive prospective single center study of 63 patients presenting with spinal global malalignment who underwent correction by PSO. Function was assessed by the Oswestry disability index (ODI), a visual analog scale of lumbar pain (VAS) and a SF-36 questionnaire. Radiographic analyses of pre- and post-operative pelvic-spinal parameters were performed on X-rays obtained by EOS((r)) imaging after 3D modeling. Global analysis and analysis of sub-groups as a function of pelvic incidence were performed and the full balance integrated index (FBI) was calculated. RESULTS: this series showed a marked clinical improvement and significant progress of functional scores. Global post operative radiological analysis showed a significant improvement in all pelvic and spinal parameters. The mean correction obtained after PSO was 31.7 degrees +/- 8.4 degrees , hence global improvement of lumbar lordosis of 22 degrees . The sagittal vertical angle (SVA) decreased from +9 cm before surgery to +4.3 cm after surgery. Sub-group analysis demonstrated greater improvement in pelvic tilt, sacral slope and spinal parameters of patients with a small or moderate pelvic incidence; all had an FBI index <10 degrees . Most of the pelvic and spinal parameters of patients with a large pelvic incidence were insufficiently corrected and they had an FBI index >10 degrees CONCLUSION: PSO is a surgical procedure enabling correction of multiplane rigid spinal deformities that require major sagittal correction. It was seen to be highly effective in patients with a small or moderate pelvic incidence (PI <60 degrees ) but was sometimes less effective in patients with large pelvic incidence due to insufficient lordosis correction. Clinical results were highly correlated with the value of the FBI index. PMID- 26861731 TI - The AhR is involved in the regulation of LoVo cell proliferation through cell cycle-associated proteins. AB - Some ingredients in foods can activate the aryl hydrocarbon receptor (AhR) and arrest cell proliferation. In this study, we hypothesized that 6-formylindolo [3, 2-b] carbazole (FICZ) arrests the cell cycle in LoVo cells (a colon cancer line) through the AhR. The AhR agonist FICZ and the AhR antagonist CH223191 were used to treat LoVo cells. Real-time PCR and Western blot analyses were performed to detect the expression of the AhR, CYP1A1, CDK4, cyclinD1, cyclin E, CDK2, P27, and pRb. The distribution and activation of the AhR were detected with immunofluorescence. A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometric analysis were performed to measure cell viability, cell cycle stage, and apoptosis. Our results show that FICZ inhibited LoVo cell proliferation by inducing G1 cell cycle arrest but had no effect on epithelial apoptosis. Further analysis found that FICZ downregulated cyclinD1 and upregulated p27 expression to arrest Rb phosphorylation. The downregulation of cyclinD1 and upregulation of p27 were abolished by co-treatment with CH223191. We conclude that the AhR, when activated by FICZ (an endogenous AhR ligand), can arrest the cell cycle and block LoVo cell proliferation. PMID- 26861732 TI - Development of an in-House TaqMan Real-Time PCR-Based Method to Detect Residual Host Cell DNA in HBV Vaccine. AB - Biological therapeutic products such as recombinant hepatitis B virus (HBV) vaccine, produced by microbial fermentation in complex media, should be evaluated for host cell DNA contamination in purification steps. Eliminating these contaminations increases the efficacy of the vaccine and decreases its side effects. The objective of the present study is to trace the residual host cell DNA (HCD) in recombinant HBV vaccine by developing a TaqMan Real-Time PCR method which is more sensitive, specific, and reproducible than traditional methods such as Picogreen analysis and Threshold DNA assay. Primers and a probe were designed for the most highly conserved regions of Pichia pastoris genome. To determine the specificity of the assay, in addition to performing a BLAST for the primers and the probe in NCBI nucleotide database, 20 different human genomes and 8 bacterial and viral genomes were used. Moreover, serial dilutions of plasmids, from 10(2) to 10(7) copies/MUL (from 0.00064 to 6.4 pg/MUL), were prepared to find the sensitivity and the limit of detection (LOD) of the assay. Using 28 different genome samples, the specificity of the assay was determined to be 100 %. In addition, the sensitivity and LOD of the method was 0.39 * 10(-5) pg/MUL. Moreover, the reproducibility of the assay based on intra- and inter-assay was 1.03 and 1.06 %, respectively. Considering the suitable specificity and sensitivity, ease of use, relatively low cost, and rapidity of the assay, it can be a reproducible and sensitive method to examine recombinant vaccines for P. pastoris residual DNA. PMID- 26861733 TI - Control of Grifola frondosa Morphology by Agitation and Aeration for Improving Mycelia and Exo-Polymer Production. AB - The present study describes the improved mycelia and exo-polymer production under control of Grifola frondosa morphology by changing the aeration rate and agitation intensity in a 25-L stirred fermentor. The aeration rate of 1.0 vvm yielded a highest mycelia biomass of 24.754 g/L with the lowest pellet percentage of 20.5 %. The maximum exo-polymer (2.324 g/L) was achieved at 0.75 vvm with mycelia polysaccharide production (0.321 g/g), whereas clumps and filaments dominated the ratios of 45.6 and 33.9 %, respectively. The change of aeration rate and agitation intensity had slight influence on the monosaccharide compositions in exo-polymers and significantly affected glucose and mannose contents in the mycelia polysaccharides. These findings will provide a clue for exploring the relationship between fermentation parameters, morphologies, and polysaccharide synthesis pathway of G. frondosa. PMID- 26861735 TI - Personality traits, gender differences and symptoms of anhedonia: What does the Hospital Anxiety and Depression Scale (HADS) measure in nonclinical settings? AB - In healthy populations men report more depressive symptoms than women when depression is measured by the Hospital Anxiety and Depression Scale (HADS). This study aims to investigate the role of neuroticism and extroversion in symptom reporting by men and women and whether anhedonia can explain these reversed gender differences in depression observed when using HADS. HADS, Positive and Negative Affect Schedule (PANAS) and NEO Five Factor Inventory (NEO FFI) were administered twice to a sample of university students. Number of subjects at T1 was 372 and 160 at T2, measured two months apart. Men had a higher average score on depressive symptoms measured by HADS-D compared to women (p = 0.029). Women scored higher than men on HADS-A (p = 0.012), neuroticism (p < 0.001) and PANAS negative affect (p < 0.029). No significant gender differences were observed in extroversion and positive affect. Test-retest stabilities on HADS-A and HADS-D were high. Neuroticism predicted HADS-A at Time 2. Gender, extroversion, and neuroticism predicted HADS-D at Time 2. The anhedonic content in HADS may be a plausible explanation of reversed gender differences in the HADS depression scale. HADS-D represents a specific anhedonic subtype of depression where symptom reporting reflects dispositional tendencies related specifically to extroversion. PMID- 26861734 TI - Human lung-derived mesenchymal stem cell-conditioned medium exerts in vitro antitumor effects in malignant pleural mesothelioma cell lines. AB - BACKGROUND: The soluble factors secreted by mesenchymal stem cells are thought to either support or inhibit tumor growth. Herein, we investigated whether the human lung-derived mesenchymal stem cell-conditioned medium (hlMSC-CM) exerts antitumor activity in malignant pleural mesothelioma cell lines H28, H2052 and Meso4. METHODS: hlMSC-CM was collected from the human lung-derived mesenchymal stem cells. Inhibition of tumor cell growth was based on the reduction of cell viability and inhibition of cell proliferation using the XTT and BrdU assays, respectively. Elimination of tumor spheroids was assessed by the anchorage independent sphere formation assay. The cytokine profile of hlMSC-CM was determined by a chemiluminescence-based cytokine array. RESULTS: Our data showed that hlMSC-CM contains a broad range of soluble factors which include: cytokines, chemokines, hormones, growth and angiogenic factors, matrix metalloproteinases, metalloproteinase inhibitors and cell-cell mediator proteins. The 48- and 72-hour hlMSC-CM treatments of H28, H2052 and Meso4 cell lines elicited significant decreases in cell viability and inhibited cell proliferation. The 72-hour hlMSC CM incubation of H28 cells completely eliminated the drug-resistant sphere forming cells, which is more potent than twice the half maximal inhibitory concentration of cisplatin. CONCLUSIONS: Our findings indicate that the cell-free hlMSC-CM confers in vitro antitumor activities via soluble factors in the tested mesothelioma cells and, hence, may serve as a therapeutic tool to augment the current treatment strategies in malignant pleural mesothelioma. PMID- 26861736 TI - Radiosynthesis and preliminary biological evaluation of a new (18)F-labeled triethylene glycol derivative of triphenylphosphonium. AB - Delocalized lipophilic cations such as [(18)F]fluorobenzyltriphenylphosphonium ([(18)F]FBnTP) can accumulate in mitochondria and have been used in myocardial perfusion imaging (MPI). In this study, we established a simplified method for [(18)F]FBnTP synthesis using triphenylphosphine hydrobromide (PPh3 *HBr) without preparing an intermediate that contains benzyl bromide structure. Applying this new method, we synthesized and evaluated a novel (18)F-labeled PEGylated BnTP derivative ([(18)F]FPEGBnTP). In vitro cellular uptake study demonstrated that [(18)F]FPEGBnTP accumulated in cells in proportion to the relative intensity of mitochondrial membrane potential. Biodistribution study revealed that the heart : liver uptake ratio of [(18)F]FPEGBnTP (4.00 at 60 min) was superior to that of [(18)F]FBnTP (1.50 at 60 min). However, [(18)F]FPEGBnTP showed slow blood clearance and high radioactivity uptake in bone at 120-min post-injection. These results imply the possibility of [(18)F]FPEGBnTP being used as a MPI agent. However, there is a need of further structural optimization and flow-dependent uptake study. PMID- 26861737 TI - Efficacy of Intraoperative Dexmedetomidine Compared with Placebo for Postoperative Pain Management: A Meta-Analysis of Published Studies. AB - INTRODUCTION: Dexmedetomidine (Dex) has sedative, analgesic, and anesthetic sparing effects. This meta-analysis examines demonstrated intraoperative and postoperative effects of intraoperative Dex administration during pediatric surgery. METHODS: A search for randomized placebo-controlled trials was conducted to identify clinical trials examining intraoperative Dex use in children, infants, and neonates. Primary outcome was postoperative opioid consumption; secondary outcomes were: postoperative pain intensity and postoperative nausea and vomiting (PONV). RESULTS: Fourteen randomized controlled trials performed during painful procedures were analyzed. Intraoperative Dex administration was associated with significantly reduced postoperative opioid consumption in the postanesthesia care unit [PACU; risk ratio (RR) = 0.31 (0.17, 0.59), I (2) = 76%, p < 0.0001 and cumulative z score using trial sequential analysis], decreased pain intensity in PACU [standardized mean difference (SMD) = -1.18 (-1.88, 0.48), I (2) = 91%, p < 0.0001] but had no effect upon PONV incidence [RR = 0.67 (0.41, 1.08), I (2) = 0%, p = 0.48]. Subgroup analyses found administering Dex during adenotonsillectomy and using a bolus <0.5 ug/kg (irrespective to the use of a continuous administration) without effects on studies outcomes. Heterogeneity was high among results and a high suspicion of publication bias was present for all analyzed outcomes. CONCLUSIONS: This meta-analysis shows that intraoperative Dex administration in children reduces postoperative opioids consumption and postoperative pain in PACU. According to our results, optimal bolus dose was found to be >=0.5 ug/kg. Future studies have to explore this particular point and the postoperative analgesic effects of Dex during longer periods. PMID- 26861738 TI - Improved progression free survival for patients with diabetes and locally advanced non-small cell lung cancer (NSCLC) using metformin during concurrent chemoradiotherapy. AB - BACKGROUND AND PURPOSE: The aim was to investigate whether the use of metformin during concurrent chemoradiotherapy (cCRT) for locally advanced non-small cell lung cancer (NSCLC) improved treatment outcome. MATERIAL AND METHODS: A total of 682 patients were included in this retrospective cohort study (59 metformin users, 623 control patients). All received cCRT in one of three participating radiation oncology departments in the Netherlands between January 2008 and January 2013. Primary endpoint was locoregional recurrence free survival (LRFS), secondary endpoints were overall survival (OS), progression-free survival (PFS) and distant metastasis free survival (DMFS). RESULTS: No significant differences in LRFS or OS were found. Metformin use was associated with an improved DMFS (74% versus 53% at 2 years; p=0.01) and PFS (58% versus 37% at 2 years and a median PFS of 41 months versus 15 months; p=0.01). In a multivariate cox-regression analysis, the use of metformin was a statistically significant independent variable for DMFS and PFS (p=0.02 and 0.03). CONCLUSIONS: Metformin use during cCRT is associated with an improved DMFS and PFS for locally advanced NSCLC patients, suggesting that metformin may be a valuable treatment addition in these patients. Evidently, our results merit to be verified in a prospective trial. PMID- 26861739 TI - How long does it take? An analysis of volumetric image assessment time. AB - This work measured time taken to integrate image-guidance with CBCTs in routine clinical practice for patients treated between 2007 and 2010 across eight linear accelerators. 117,301 CBCTs from 4592 patients across thirteen disease sites were included. The mean image assessment decision time was 79s. Decision time was correlated with setup displacement magnitude. PMID- 26861741 TI - Field study on evaluation of the efficacy and usability of two disinfectants for drinking water treatment at small cattle breeders and dairy cattle farms. AB - The hygienic quality of drinking water for cattle originated from different sources together with the efficacy and usability of two types of disinfectants against waterborne pathogens were assessed for small cattle breeders and dairy cattle farms. A total of 120 drinking water samples were collected from water troughs representing three different water sources commonly used for cattle drinking (tap, underground and surface water; n = 65, 25, and 30, respectively). Collected samples were cultured for isolation and identification of pathogenic bacteria using serological techniques and PCR. The bactericidal efficacy of the disinfectants, sodium dichloroisocyanurate (NaDCC) and hydrogen peroxide (H2O2) 50%, at different concentrations were evaluated by the determination of total viable and coliform counts of water prior and postwater treatment. In small cattle breeders, Escherichia coli was the most prevalent bacterial isolates from surface water (56.7%) followed by Staphylococcus aureus (36.7%), Salmonella spp. (26.7%), Streptococcus faecalis (23.3%), Shigella flexneri (16.7%), Proteus spp. (16.7%), and Klebsiella pneumonae (10.0 %) at X(2) = 9, P <= 0.01. Prior to the use of disinfectants, the averages of total bacterial and coliform counts were the highest in surface water (3.56 * 10(7), 240.0, and 38.0 CFU/100 ml, respectively). It has been found that hydrogen peroxide 50% at a concentration of 35 mg/l had a lethal effect (100 %) on indicator microorganisms compared with NaDCC at concentration of 2 mg/l. In conclusion, the higher bacterial contaminants in drinking water were found in surface water followed by tap water, particularly for small cattle breeders. Therefore, the usage of more hygienic water troughs with their regular treatment by hydrogen peroxide 50% at concentration of 35 mg/l is highly recommended to control waterborne bacteria and consequently improve and maintain the animal health. PMID- 26861740 TI - Phase I study of pre-operative continuous 5-FU and sorafenib with external radiation therapy in locally advanced rectal adenocarcinoma. AB - PURPOSE: The standard of care in locally advanced rectal cancer is preoperative treatment with fluoropyrimidine-based chemoradiotherapy. Sorafenib works synergistically with radiation and inhibits Ras/Raf, PDFGR, and VEGFR. This phase I study evaluated the safety and efficacy of sorafenib with infusional 5 fluorouracil (5-FU) and radiation in patients with locally advanced rectal cancer. METHODS AND MATERIALS: Patients with confirmed stage II or III rectal cancer were recruited in 4 cohorts of 3 patients per dose level, with an expansion cohort at the maximum tolerated dose. A 3+3 dose escalation design was used. Radiation was given in 28 fractions at 1.8 Gy (50.4 Gy) day 1-5 at all dose levels. Initial dose of sorafenib was 200mg qd and titrated up to 400mg BID to determine the MTD. Standard dose of infusional 5-FU was used (225 mg/m(2)/24h). Patients underwent surgery 6-10 weeks after neoadjuvant therapy. RESULTS: Between August 2011 and August 2014, 17 patients (median age of 54 years) were enrolled. After toxicities requiring dose interruptions were observed in cohort 1 (2 patients with grade 2 (G2) and grade 3 (G3) hand foot skin reaction and 1 patient with G2 mucositis), the protocol was amended, changing administration of chemotherapy and sorafenib from daily to days 1-5 only. With the amended protocol, the primary G3 toxicity was hypertension in 2 patients at the 200-mg adjusted dose level (day1-5) and 1 patient at the 400-mg twice daily dose level. One patient had G3 ALT elevation at 400mg, and no grade IV toxicities were observed. G1 and G2 toxicities included hand-foot skin reaction, diarrhea, mucositis, nausea, fatigue, and proctitis. No perioperative complications were seen. Two patients refused to undergo surgery. The pathological complete remission (pCR) rate was 33%, and downstaging was observed in 85.7% of patients. Median neoadjuvant rectal cancer score was 8.7. CONCLUSIONS: With the changed dosing schedule, this regimen was very well tolerated. The tumor pCR and downstaging rates are encouraging and support further clinical investigation of this regimen. PMID- 26861743 TI - Succession of phytoplankton assemblages in response to large-scale reservoir operation: a case study in a tributary of the Three Gorges Reservoir, China. AB - The Three Gorges Dam (TGD) has greatly altered ecological and environmental conditions within the reservoir region, but it is not known how these changes affect phytoplankton structure and dynamics. Here, a bimonthly monitoring program was implemented from 2007 to 2009 to study the impact of damming on phytoplankton assemblages in the backwater area of the Pengxi River (PBA). By application of the phytoplankton functional group (C strategists, competitive species; S strategists, stress-tolerant species; R strategists, rapid propagation species), seasonal changes in phytoplankton relative to environmental variations were evaluated using ordination analysis. Seasonal patterns of phytoplankton dynamics were detected during this study, with CS/S strategists causing algal blooms from mid-spring to early summer, CS/CR strategists often observed during flood season, and CS strategists dominant during mid-autumn. CR/R groups dominated during winter and caused algal blooms in February. Our results indicated that phytoplankton assemblages were directly related to reservoir operation effects. Generally, the TGD had a low water level during flood season, resulting in a relatively short hydraulic retention time and intensive variability, which supported the cooccurrence of CS and CR species. During the winter drought season, water storage in the TGD increased the water level and the hydraulic retention time in the PBA, enabling R/CR strategists to overcome the sedimentation effect and to out-compete S/CS species in winter. As expected, these diversity patterns were significantly correlated with the hydraulic retention time and nutrient limitation pattern in the PBA. This study provides strategic insight for evaluating the impacts of reservoir operations on phytoplankton adaptation. PMID- 26861742 TI - Assessment of polycyclic aromatic hydrocarbons (PAHs) contamination in surface soil of coal stockpile sites in South Kalimantan, Indonesia. AB - Concentrations, spatial distribution, and sources of 16 polycyclic aromatic hydrocarbons (PAHs), listed as priority pollutants by the United States Environmental Protection Agency (USEPA), were investigated in surface soils of three different coal stockpile, agricultural, and residential sites in South Kalimantan Province, Indonesia. Total PAHs concentration ranged from 4.69 to 22.67 mg kg(-1)-dw. PAHs concentrations in soil of coal stockpile sites were higher than those in agricultural and residential soil. A complex of petrogenic origin and pyrolytic sources was found within the study area, as suggested by the isomeric ratios of PAHs. The results of principal component analysis and multiple linear regressions (PCA/MLR) showed that three sources contributed to the PAHs in the study area, including biomass and coal combustion (48.46%), raw coal (35.49%), and vehicular emission (16.05%). The high value of total benzo[a]pyrene equivalent concentration (B[a]Peq) suggests that local residents are exposed to a high carcinogenic potential. PMID- 26861744 TI - The usefulness of low-dose CT scan in elderly patients with suspected acute lower respiratory infection in the emergency room. AB - OBJECTIVE: To evaluate the usefulness of low-dose CT (LDCT) for the diagnosis of acute lower respiratory infection (ALRI) in elderly patients in the emergency room (ER). METHODS: A total of 160 consecutive patients (mean age: 75.9 +/- 9.2 years; range: 60-97 years), who were diagnosed to have ALRI by LDCT in the ER, were enrolled in this study. Initial chest radiograph (CR) and CT patterns of ALRI were analysed, and clinical courses of patients were assessed. RESULTS: 49 patients showed negative CR, in whom the main CT patterns were diffuse bronchial wall thickening (n = 23), ground-glass opacity (n = 6), mixed centrilobular nodules and ground-glass opacity (n = 3), small consolidation (n = 8) or consolidation in the dependent lung (n = 9), while the other 111 patients with the main CT pattern of consolidation demonstrated pulmonary abnormality on CR. Pulmonary oedema (12.5%) and pleural effusion (23.1%) were associated. The rate of hospitalization, care in the intensive care unit, mortality and comorbidity were significantly higher in the CR(+)LDCT(+) group (88.3%, 36.1%, 18.2% and 59.5%) than in the CR(-)LDCT(+) group (55.1%, 8.2%, 2.0% and 38.8%; p <= 0.05). CONCLUSION: LDCT was useful for the early diagnosis of ALRI in elderly patients who showed negative initial CR. The patients with negative initial CR had main CT patterns of diffuse bronchial wall thickening, ground-glass opacity, centrilobular nodules, small consolidation or consolidation in the dependent lung on LDCT. ADVANCES IN KNOWLEDGE: The use of LDCT may be considered for the early diagnosis of ALRI in elderly patients who have high comorbidity. PMID- 26861745 TI - Prospective evaluation of prostate with transrectal spectral Doppler with biopsy correlation: a clinicopathologic study. AB - OBJECTIVES: To compare the transrectal (TR) spectral Doppler findings between benign prostatic hyperplasia group and prostate cancer group. METHODS: All the patients were assessed for adequate preparation, and informed consent was obtained prior to the procedure. The control group (n = 33) comprised patients who were negative for malignancy on biopsy. The study group (n = 22) were positive for malignancy and were also divided into three groups on the basis of the Gleason score. Study parameters included mean values for resistive index (RI), pulsatality index (PI), systolic/diastolic ratio (S/D) and peak systolic velocity (PSV). These were separately measured for bilateral capsular and urethral branches and compared between groups. In patients with unilateral tumour, these were compared between the tumour and non-tumour sides. Finally, the parameters were compared with patient's age. Mann-Whitney U test was used to evaluate the statistical significance. RESULTS: The mean values of RI, PI, S/D and PSV were found to be 0.84/1.03, 1.8/1.99, 3.93/4.45 and 15.52/16.15 cm s(-1), respectively, in the control and study groups which were not statistically significant. In patients with unilateral malignancy (n = 16), there was no significant difference from the non-tumour side. Doppler parameters showed statistically significant relationships with age. The mean of minimum RI was found to be 0.60 in patients less than 60 years of age and 0.76 in patients more than or equal to 60 years of age in the benign category (p-value = 0.014). The PI and S/D also showed significant difference in the benign category. CONCLUSION: TR spectral Doppler parameters did not reveal any significant difference in patients with or without prostatic malignancy, irrespective of the Gleason grade. Doppler parameters, however, showed significant correlation with age and were lower in younger patients. ADVANCES IN KNOWLEDGE: TR spectral Doppler is unlikely to emerge as a diagnostic and prognostic tool for prostate carcinoma. PMID- 26861747 TI - Introduction to Frontiers in Macromolecular and Supramolecular Science: Part 1. PMID- 26861746 TI - Therapeutic taping for soft tissue-based digit malrotation. AB - Patients with soft-tissue based digit malrotation often report scissoring with digit flexion, limiting functional grasp capability. This author has successfully utilized a taping technique to improve function for these patients. - Victoria Priganc, PhD, OTR, CHT, CLT, Practice Forum Editor. PMID- 26861748 TI - The Effects of Advance Care Planning Interventions on Nursing Home Residents: A Systematic Review. AB - BACKGROUND: Advance care planning (ACP) encompasses a process by which people may express and record their values and preferences for care and treatment should they lose the capacity to communicate them in the future. We believe the effects that ACP can have on the nursing home population is distinct from others and sought to gain insight into the outcomes of relevant studies on the topic. AIM: To identify the effects of ACP interventions on nursing home residents. DESIGN: Systematic review. METHODS: A comprehensive literature search was conducted using the following 4 electronic databases, Embase, Medline, PsychINFO, and CINAHL, with no limits on year or language. Gray literature search of relevant journals was also performed as was reviewing of the reference lists of all included articles. Inclusion criteria were randomized controlled trials, controlled trials, pre/post study design trials and prospective studies examining the effects of ACP on nursing home residents. A detailed narrative synthesis was compiled as the heterogeneous nature of the interventions and results precluded meta-analysis. RESULTS: The initial search yielded 4654 articles. Thirteen studies fitted inclusion criteria for analysis. The ACP interventions included (1) 5 studies evaluating educational programs; (2) 5 studies introducing or evaluating a new ACP form; (3) 2 studies introducing an ACP program with a palliative care initiative; and (4) 1 study observing the effect of do not resuscitate orders on medical treatments for respiratory infections. A range of effects of ACP was demonstrated in the study populations. Hospitalization was the most frequent outcome measure used across the included studies. Analysis found that in the nursing home population, ACP decreased hospitalization rates by 9% 26%. Of note, in the 2 studies that included mortality, the decrease in hospitalization was not associated with increased mortality. Place of death is another important effect of ACP. Analysis found significant increases in the number of residents dying in their nursing home by 29%-40%. Medical treatments being consistent with ones' wishes were increased with ACP although not to 100% compliance. Two studies showed a decrease in overall health costs. One study found an increase in community palliative care use but not in-patient hospice referrals. CONCLUSIONS: ACP has beneficial effects in the nursing home population. The types of ACP interventions vary, and it is difficult to identify superiority in effectiveness of one intervention over another. Outcome measures also vary considerably between studies although hospitalization, place of death, and actions being consistent with resident's wishes are by far the most common. Very few studies with high quality methodology have been undertaken in the area with a significant lack of randomized controlled trials. More robust studies, especially randomized controlled trials, are required to support the findings. PMID- 26861749 TI - Letter to the editor: Subsidize health. PMID- 26861750 TI - Accelerometer-determined physical activity and mortality in a national prospective cohort study: Considerations by visual acuity. AB - BACKGROUND: Previous research demonstrates that visual impairment (VI) is associated with increased all-cause mortality risk and is also associated with reduced physical activity participation. Although physical activity is reduced among those with VI, no studies have examined the relationship between physical activity and all-cause mortality across different visual function statuses, which is noteworthy of investigation as physical activity is linked with greater survival. METHODS: Data from the 2003-2006 NHANES were employed, with physical activity assessed via accelerometry and visual function assessed using the ARK 760 autorefractor. RESULTS: For those with normal vision, and after adjustments, for every 60min increase in physical activity, normal-sighted adults had an 18% (HR=0.82; 95% CI: 0.72-0.93) reduced risk of all-cause mortality. Similarly, after adjustments and for every 60min increase in physical activity for those with uncorrected refractive error and VI, respectively, there was a 15% (HR=0.85; 95% CI: 0.72-1.00) and 35% (HR=0.65; 95% CI: 0.43-0.98) reduced risk of all-cause mortality. Among all three visual status groups, sedentary behavior was not associated with mortality status. CONCLUSION: Among those with varying degrees of visual loss, sedentary behavior was not associated with mortality, but physical activity demonstrated survival benefits. PMID- 26861751 TI - Work, household, and leisure-time physical activity and risk of mortality in the EPIC-Spain cohort. AB - OBJECTIVE: Large-scale longitudinal data on the association of domain-specific physical activity (PA) and mortality is limited. Our objective was to evaluate the association of work, household (HPA), and leisure time PA (LTPA) with overall and cause-specific mortality in the EPIC-Spain study. METHODS: 38,379 participants (62.4% women), 30-65years old, and free of chronic disease at baseline were followed-up from recruitment (1992 - 1996) to December 31st, 2008 to ascertain vital status and cause of death. PA was evaluated at baseline and at a 3-year follow-up with a validated questionnaire (EPIC-PAQ) and combined variables were used to classify the participants by sub-domains of PA. Associations with overall, cancer, and cardiovascular mortality risks were assessed using competing risk Cox regression models adjusted by potential confounders. RESULTS: After 13.6years of mean follow-up, 1371 deaths were available for analyses. HPA was strongly associated to reduced overall (hazard ratio (HR) for Q4 vs. Q1=0.47 (0.34, 0.64)) and cause-specific mortalities in women and to lower cancer mortality in men (P for trend=0.004), irrespective of age, education, and lifestyle and morbidity variables. LTPA was associated with lower mortality in women (HR for Q4 vs. Q1=0.71 (0.52, 0.98)), but not men. No relationships were found between sedentariness at work and overall mortality. CONCLUSIONS: HPA was associated to lower mortality risk in men and women from the EPIC-Spain cohort, whereas LTPA also contributed to reduce risk of death in women. Considering the large proportion of total daily PA that HPA represents in some population groups, these results are of public health importance. PMID- 26861752 TI - Factors associated with heavy drinking among off-reserve First Nations and Metis youth and adults: Evidence from the 2012 Canadian Aboriginal Peoples Survey. AB - Objective . Aboriginal people in Canada are at higher risk to heavy alcohol consumption than are other Canadians. The objective of this study was to examine a set of culturally specific correlates of heavy drinking among First Nations and Metis youth and adults. Methods . Demographic, geographic, socioeconomic and health-related variables were also considered. Data were used from Statistics Canada's 2012 Aboriginal Peoples Survey to predict heavy drinking among 14,410 First Nations and Metis 15years of age and older. Separate sets of binary sequential logistic regression models were estimated for youth and adults. Results . Among youth, those who had hunted, fished or trapped within the last year were more likely to be heavy drinkers. In addition, current smokers and those who most frequently participated in sports were at higher odds of heavy alcohol consumption. Among adults, respondents who had hunted, fished or trapped within the last year were more likely to drink heavily. On the other hand, those who had made traditional arts or crafts within the last year were less likely to drink heavily. Conclusions . Men, younger adults, smokers, those who were unmarried, those who had higher household incomes, and those who had higher ratings of self-perceived health were more likely to be heavy drinkers. Efforts aimed at reducing the prevalence of heavy drinking among this population may benefit from considering culturally specific factors, in addition to demographic variables and co-occurring health-risk behaviors. PMID- 26861753 TI - The human organic cation transporter OCT1 mediates high affinity uptake of the anticancer drug daunorubicin. AB - Anthracyclines such as daunorubicin are anticancer agents that are transported into cells, and exert cytotoxicity by blocking DNA metabolism. Although there is evidence for active uptake of anthracyclines into cells, the specific transporter involved in this process has not been identified. Using the high-grade serous ovarian cancer cell line TOV2223G, we show that OCT1 mediated the high affinity (Km ~ 5 MUM) uptake of daunorubicin into the cells, and that micromolar amounts of choline completely abolished the drug entry. OCT1 downregulation by shRNA impaired daunorubicin uptake into the TOV2223G cells, and these cells were significantly more resistant to the drug in comparison to the control shRNA. Transfection of HEK293T cells, which accommodated the ectopic expression of OCT1, with a plasmid expressing OCT1-EYFP showed that the transporter was predominantly localized to the plasma membrane. These transfected cells exhibited an increase in the uptake of daunorubicin in comparison to control cells transfected with an empty EYFP vector. Furthermore, a variant of OCT1, OCT1-D474C-EYFP, failed to enhance daunorubicin uptake. This is the first report demonstrating that human OCT1 is involved in the high affinity transport of anthracyclines. We postulate that OCT1 defects may contribute to the resistance of cancer cells treated with anthracyclines. PMID- 26861755 TI - Long-menu questions in computer-based assessments: a retrospective observational study. AB - BACKGROUND: Computer based assessments of paediatrics in our institution use series of clinical cases, where information is progressively delivered to the students in a sequential order. Three types of formats are mainly used: Type A (single answer), Pick N, and Long-menu. Long-menu questions require a long, hidden list of possible answers: based on the student's initial free text response, the program narrows the list, allowing the student to select the answer. This study analyses the psychometric properties of Long-menu questions compared with the two other commonly used formats: Type A and Pick N. METHODS: We reviewed the difficulty level and discrimination index of the items in the paediatric exams from 2009 to 2015, and compared the Long-menu questions with the Type A and Pick N questions, using multiple-way analyses of variances. RESULTS: Our dataset included 13 exam sessions with 855 students and 558 items included in the analysis, 212 (38 %) Long-menu, 201 (36 %) Pick N, and 140 Type A (25 %) items. There was a significant format effect associated with both level of difficulty (p = .005) and discrimination index (p < .001). Long-menu questions were easier than Type A questions(+5.2 %; 95 % CI 1.1-9.4 %), and more discriminative than both Type A (+0.07; 95 % CI 0.01-0.14), and Pick N (+0.10; 95 % CI 0.05-0.16) questions. CONCLUSIONS: Long-menu questions show good psychometric properties when compared with more common formats such as Type A or Pick N, though confirmatory studies are needed. They provide more variety, reduce the cueing effect, and thus may more closely reflect real life practice than the other item formats inherited from paper-based examination that are used during computer-based assessments. PMID- 26861756 TI - [Clinical examination, imaging and therapy of Osgood-Schlatter's disease]. AB - BACKGROUND: Osgood-Schlatter's disease represents an often seen painful knee illness of temporary duration in adolescent sportsmen, caused by severe stress to the tibial apophysis. RESULTS: A study in 29 consecutive patients (? 12,7 yrs, 77 % male, 67 % non-dominant side affected, 4 patients both knee joints affected, always pain after performance, high sports activity in football, basketball, gymnastics/ballett, 41 % shortening of m. rectus fem.) shows that pure clinical diagnosis is sufficient. DISCUSSION: Imaging is only necessary in case of suspected concurrent origin, as it does not yield unique results and does not support therapy nor prognosis. Patients reduce their performance on their own. Late pain occurs at the apophyseal protuberance due to local compression. Restrictive recommendations to patients to leave their sport activity are not justified. PMID- 26861754 TI - Induction of WNT11 by hypoxia and hypoxia-inducible factor-1alpha regulates cell proliferation, migration and invasion. AB - Changes in cellular oxygen tension play important roles in physiological processes including development and pathological processes such as tumor promotion. The cellular adaptations to sustained hypoxia are mediated by hypoxia inducible factors (HIFs) to regulate downstream target gene expression. With hypoxia, the stabilized HIF-alpha and aryl hydrocarbon receptor nuclear translocator (ARNT, also known as HIF-beta) heterodimer bind to hypoxia response elements (HREs) and regulate expression of target genes. Here, we report that WNT11 is induced by hypoxia in many cell types, and that transcription of WNT11 is regulated primarily by HIF-1alpha. We observed induced WNT11 expression in the hypoxic area of allograft tumors. In addition, in mice bearing orthotopic malignant gliomas, inhibition with bevacizumab of vascular endothelial growth factor, which is an important stimulus for angiogenesis, increased nuclear HIF 1alpha and HIF-2alpha, and expression of WNT11. Gain- and loss-of-function approaches revealed that WNT11 stimulates proliferation, migration and invasion of cancer-derived cells, and increases activity of matrix metalloproteinase (MMP) 2 and 9. Since tumor hypoxia has been proposed to increase tumor aggressiveness, these data suggest WNT11 as a possible target for cancer therapies, especially for tumors treated with antiangiogenic therapy. PMID- 26861757 TI - [Orthopedic shoe treatment: Inserts]. AB - The use of inserts and orthopedic shoe adjustment represents an essential component of the conservative therapy of degenerative diseases and deformities of the musculoskeletal system. Inserts can have supportive, bedding and corrective effects and are used in particular for complaints of the feet and ankles. The combination of diverse materials allows a high level of cushioning and supporting features and corresponding longevity to be accomplished. The production is carried out on an individual basis and if necessary computer-assisted in order to achieve an optimal fit. For severe and rigid deformities the formation of pressure ulcers can be prevented by orthopedic shoe adjustment and by the use of orthopedic tailor-made shoes. PMID- 26861758 TI - The role of practice and strategy in mental rotation training: transfer and maintenance effects. AB - Research in the domain of spatial abilities is now focusing on whether spatial abilities can be trained, and whether this can produce gains and maintenance effects in other, untrained skills. The aim of the present study was to assess the benefit and maintenance effects of two types of mental rotation training, one based on mental rotation practice alone, the other combining mental rotation practice with the use of a spatial (rotation) strategy. Seventy-two females took part in the study: 24 practiced with a rotation task that involved comparing pairs of 3D objects [the mental rotation (MR) group], 24 were taught to use the rotation strategy while practicing with the rotation task [the strategy + mental rotation (S + MR) group], and 24 were involved in parallel non-spatial activities (the active control group). Transfer effects were sought on both untrained spatial tasks (testing object rotation and perspective taking) and fluid ability tasks; self-reported strategy use was also examined. Our results showed short term benefits and maintenance effects in the MR and the S + MR groups in terms of their accuracy in both the MR tasks considered (a 3D same/different task, and the Mental Rotations Test). The S + MR group was more accurate at follow-up than at post-test in both MR tasks, and reported using the rotation strategy in association with the tasks; this group was also more accurate at follow-up than at pre-test in the perspective-taking and fluid intelligence tasks. These findings are discussed from the spatial cognition standpoint and with reference to the (rotation) training literature. PMID- 26861759 TI - Segmental forearm bone injuries in children: classification and treatment. AB - BACKGROUND: Fractures of the forearm bones in children are a very frequent injury, while segmental injuries of the forearm bones are very rare and have not been sufficiently examined. In this retrospective study, segmental injuries involving the radius, the ulna or both in children are classified and treatment outcome is presented. MATERIALS AND METHODS: Bone injury included any type of fracture or dislocation; segmental bone injury indicated the occurrence of more than one traumatic injury throughout the whole extent of each forearm bone. A total of 17 patients with 22 segmental bone injuries were identified and classified. Of these injuries, 12 involved the radius and 10 the ulna. The mean age at the time of injury was 8.9 years (range 3-13). In all cases, conservative treatment was the first treatment option; in three cases, however, surgical treatment was necessary. RESULTS: All injuries were classified into five types using the new nomenclature. Patients were evaluated after an average follow-up of 10.4 years. Union was noted in all cases without any complications. The function results were rated as excellent in 15 cases and satisfactory in 2 cases. CONCLUSIONS: An inclusive classification system for segmental injuries of the forearm bones in children is presented. The proposed classification is a practical and utilitarian scheme that classified the patients of this report as well as all case reports previously published in the literature. It revealed that a wide variety of segmental injuries may be diagnosed following forearm injuries in children. This report also provided useful information that may influence the treatment of these complex injuries indicating that conservative treatment may be considered the first treatment option, and that primary surgical treatment is not justified. LEVEL OF EVIDENCE: Level V. PMID- 26861760 TI - The anterolateral ligament of the knee: unwrapping the enigma. Anatomical study and comparison to previous reports. AB - BACKGROUND: It has been suggested that the anterolateral ligament (ALL) of the knee may have importance in limiting rotational instability, and reconstruction may prevent a continued pivot-shift following anterior cruciate ligament surgery. However, the anatomy of this ligament has not been consistently reported in recent publications. We describe our experience of cadaveric dissection with reference to other published work. MATERIALS AND METHODS: Eleven fresh-frozen cadaveric knees were dissected using a standard technique. The ALL tissue was identified with internal rotation of the tibia and varus stress. Measurements were made using a digital caliper and details of the origin and insertion were recorded. RESULTS: The ALL was identified in ten of the 11 cadavers. The only specimen in which it was not identified was found to also have an anterior cruciate ligament deficiency. The mean dimensions were: length 40.1 (+/- 5.53) mm, width 4.63 (+/- 1.39) mm, thickness 0.87 (+/- 0.18) mm. The femoral origin was posterior and proximal to the lateral collateral ligament attachment in six knees, anterior and distal in three knees, and at the same site in one knee. The tibial insertion was a mean 17.7 (+/- 2.95) mm from Gerdy's tubercle (GT) and 12.3 (+/- 3.55) mm from the fibula head (FH). This was 59.5 (+/- 5.44) % from GT to FH. CONCLUSIONS: This anatomical data adds to previous information about the ALL. Our results support the finding that the ALL is a capsular thickening with meniscal attachment. The findings will help to guide the further work required to define the indications for reconstruction and appropriate grafts. PMID- 26861762 TI - Current tools for the optimization of embryo transfer technique for recurrent implantation failure. AB - Recurrent implantation failure (RIF) is the name of a clinical condition coined following the widespread use of in-vitro fertilization (IVF), which has allowed compartmentalization of several different fertility treatments. Its definition is dynamic and depends on the population of patients studied, as well as the type and quality of clinical practice. In this review we survey the tools which are currently used in order to improve treatment outcome in patients with recurrent implantation failure. Some of these practices are more commonly or firmly established than others, however the beneficial contribution of most of these tools to improve reproductive outcomes among patients with recurrent implantation failure still lacks proper scientific validation. PMID- 26861761 TI - Prediction of Immunomodulatory potential of an RNA sequence for designing non toxic siRNAs and RNA-based vaccine adjuvants. AB - Our innate immune system recognizes a foreign RNA sequence of a pathogen and activates the immune system to eliminate the pathogen from our body. This immunomodulatory potential of RNA can be used to design RNA-based immunotherapy and vaccine adjuvants. In case of siRNA-based therapy, the immunomodulatory effect of an RNA sequence is unwanted as it may cause immunotoxicity. Thus, we developed a method for designing a single-stranded RNA (ssRNA) sequence with desired immunomodulatory potentials, for designing RNA-based therapeutics, immunotherapy and vaccine adjuvants. The dataset used for training and testing our models consists of 602 experimentally verified immunomodulatory oligoribonucleotides (IMORNs) that are ssRNA sequences of length 17 to 27 nucleotides and 520 circulating miRNAs as non-immunomodulatory sequences. We developed prediction models using various features that include composition-based features, binary profile, selected features, and hybrid features. All models were evaluated using five-fold cross-validation and external validation techniques; achieving a maximum mean Matthews Correlation Coefficient (MCC) of 0.86 with 93% accuracy. We identified motifs using MERCI software and observed the abundance of adenine (A) in motifs. Based on the above study, we developed a web server, imRNA, comprising of various modules important for designing RNA-based therapeutics (http://crdd.osdd.net/raghava/imrna/). PMID- 26861763 TI - Reducing Co-Ordering of Amylase and Lipase Testing at an Academic Medical Center: A Quality Improvement Project. PMID- 26861764 TI - Carrier density independent scattering rate in SrTiO3-based electron liquids. AB - We examine the carrier density dependence of the scattering rate in two- and three-dimensional electron liquids in SrTiO3 in the regime where it scales with T(n) (T is the temperature and n <= 2) in the cases when it is varied by electrostatic control and chemical doping, respectively. It is shown that the scattering rate is independent of the carrier density. This is contrary to the expectations from Landau Fermi liquid theory, where the scattering rate scales inversely with the Fermi energy (EF). We discuss that the behavior is very similar to systems traditionally identified as non-Fermi liquids (n < 2). This includes the cuprates and other transition metal oxide perovskites, where strikingly similar density-independent scattering rates have been observed. The results indicate that the applicability of Fermi liquid theory should be questioned for a much broader range of correlated materials and point to the need for a unified theory. PMID- 26861765 TI - Ultra-high performance liquid chromatography with linear ion trap-Orbitrap hybrid mass spectrometry combined with a systematic strategy based on fragment ions for the rapid separation and characterization of components in Stellera chamaejasme extracts. AB - Stellera chamaejasme, a famous toxic herb, has been used in traditional Chinese medicine to treat various diseases. For decades, increasing attention in modern pharmacological studies has been drawn to S. chamaejasme because of its potential anti-tumor, anti-virus, and anti-fungus activities. However, due to the intrinsic complexity of chemical constitutes, hardly any investigations formed an overall recognition for the chemical profiles of this herb. In this study, a rapid and sensitive ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry method was developed to characterize the chemical components of S. chamaejasme extracts. Based on optimized ultra-high performance liquid chromatography and mass spectrometry conditions and systematic fragment ions-based strategy, a total of 47 components including flavones, diterpenes, coumarins, and lignans were simultaneously detected and identified or tentatively identified for the first time. The MS(n) fragmentation patterns of all the characterized compounds in positive or negative electrospray ionization modes were also explored and summarized. These results provided essential data for further pharmacological research on S. chamaejasme. Moreover, the method was demonstrated to be an efficient tool for rapid qualitative analysis of secondary metabolites from natural resources. PMID- 26861767 TI - Complex-shaped three-dimensional multi-compartmental microparticles generated by diffusional and Marangoni microflows in centrifugally discharged droplets. AB - We report a versatile method for the generation of complex-shaped three dimensional multi-compartmental (3D-MC) microparticles. Complex-shaped microparticles have recently received much attention for potential application in self-assemblies, micromachines, and biomedical and environmental engineering. Here, we have developed a method based on 3D nonequilibrium-induced microflows (Marangoni and diffusional flows) of microdroplets that are discharged from the tip of a thin capillary in a simple centrifugal microfluidic device. The microparticle shapes can be tuned by the partial dissolution of specific compartments and by the deformation of the precursor microdroplets by manipulating the 3D microflows. We believe that this method will have wide applications in nano- and microscience and technologies. PMID- 26861766 TI - Pure and stable metallic phase molybdenum disulfide nanosheets for hydrogen evolution reaction. AB - Metallic-phase MoS2 (M-MoS2) is metastable and does not exist in nature. Pure and stable M-MoS2 has not been previously prepared by chemical synthesis, to the best of our knowledge. Here we report a hydrothermal process for synthesizing stable two-dimensional M-MoS2 nanosheets in water. The metal-metal Raman stretching mode at 146 cm(-1) in the M-MoS2 structure, as predicted by theoretical calculations, is experimentally observed. The stability of the M-MoS2 is associated with the adsorption of a monolayer of water molecules on both sides of the nanosheets, which reduce restacking and prevent aggregation in water. The obtained M-MoS2 exhibits excellent stability in water and superior activity for the hydrogen evolution reaction, with a current density of 10 mA cm(-2) at a low potential of 175 mV and a Tafel slope of 41 mV per decade. PMID- 26861768 TI - Chelation-assisted Pd-catalysed ortho-selective oxidative C-H/C-H cross-coupling of aromatic carboxylic acids with arenes and intramolecular Friedel-Crafts acylation: one-pot formation of fluorenones. AB - Pd-Catalysed ortho-selective oxidative C-H/C-H cross-coupling of aromatic carboxylic acids with arenes and subsequent intramolecular Friedel-Crafts acylation has been accomplished for the first time through a chelation-assisted C H activation strategy. Starting from the readily available substrates, a variety of fluorenone derivatives are obtained in one pot. The direct use of naturally occurring carboxylic acid functionalities as directing groups avoids unnecessary steps for installation and removal of an extra directing group. PMID- 26861770 TI - Synthesis, characterization and in vitro evaluation of exquisite targeting SPIONs PEG-HER in HER2+ human breast cancer cells. AB - A stable, biocompatible and exquisite SPIONs-PEG-HER targeting complex was developed. Initially synthesized superparamagnetic iron oxide nanoparticles (SPIONs) were silanized using 3-aminopropyltrimethoxysilane (APS) as the coupling agent in order to allow the covalent bonding of polyethylene glycol (PEG) to the SPIONs to improve the biocompatibility of the SPIONs. SPIONs-PEG were then conjugated with herceptin (HER) to permit the SPIONs-PEG-HER to target the specific receptors expressed over the surface of the HER2+ metastatic breast cancer cells. Each preparation step was physico-chemically analyzed and characterized by a number of analytical methods including AAS, FTIR spectroscopy, XRD, FESEM, TEM, DLS and VSM. The biocompatibility of SPIONs-PEG-HER was evaluated in vitro on HSF-1184 (human skin fibroblast cells), SK-BR-3 (human breast cancer cells, HER+), MDA-MB-231 (human breast cancer cells, HER-) and MDA MB-468 (human breast cancer cells, HER-) cell lines by performing MTT and trypan blue assays. The hemolysis analysis results of the SPIONs-PEG-HER and SPIONs-PEG did not indicate any sign of lysis while in contact with erythrocytes. Additionally, there were no morphological changes seen in RBCs after incubation with SPIONs-PEG-HER and SPIONs-PEG under a light microscope. The qualitative and quantitative in vitro targeting studies confirmed the high level of SPION-PEG-HER binding to SK-BR-3 (HER2+ metastatic breast cancer cells). Thus, the results reflected that the SPIONs-PEG-HER can be chosen as a favorable biomaterial for biomedical applications, chiefly magnetic hyperthermia, in the future. PMID- 26861769 TI - Guideline-concordant weight-loss programs in an urban area are uncommon and difficult to identify through the internet. AB - OBJECTIVE: To determine the reliability of Internet-based information on community-based weight-loss programs and grade their degree of concordance with 2013 American Heart Association, American College of Cardiology, and The Obesity Society weight-management guidelines. METHODS: An online search was conducted for weight-loss programs in the Maryland-Washington, DC-Virginia corridor. Content analysis was performed to abstract program components from their websites, and then 80 programs were randomly selected for a telephone survey to verify this information. Reliability of Internet information was determined in comparison with telephone interview responses. RESULTS: Of the 191 programs, 1% were graded as high, 8% as moderate, and 91% as low with respect to guideline concordance based on website content. Fifty-two programs participated in the telephone survey (65% response rate). Program intensity, diet, physical activity, and use of behavioral strategies were underreported on websites as compared to description of these activities during the phone interview. Within the subsample, 6% of programs were graded as high based on website information, whereas 19% were graded as high after the telephone interview. CONCLUSIONS: Most weight-loss programs in an urban, mid-Atlantic region do not currently offer guideline concordant practices and fail to disclose key information online, which may make clinician referrals challenging. PMID- 26861771 TI - First report of Y-linked genes in the kissing bug Rhodnius prolixus. AB - BACKGROUND: Due to an abundance of repetitive DNA, the annotation of heterochromatic regions of the genome such as the Y chromosome is problematic. The Y chromosome is involved in key biological functions such as male-fertility and sex-determination and hence, accurate identification of its sequences is vital. The hemipteran insect Rhodnius prolixus is an important vector of Chagas disease, a trypanosomiasis affecting 6-7 million people worldwide. Here we report the identification of the first Y-linked genes of this species. RESULTS: The R. prolixus genome was recently sequenced using separate libraries for each sex and the sequences assembled only with male reads are candidates for Y linkage. We found 766 such candidates and PCR tests with the ten largest ones, confirmed Y linkage for all of them, suggesting that "separate libraries" is a reliable method for the identification of Y-linked sequences. BLAST analyses of the 766 candidate scaffolds revealed that 568 scaffolds contained genes or part of putative genes. We tested Y-linkage for 36 candidates and found that nine of them are Y-linked (the PCR results for the other 25 genes were inconclusive or revealed autosomal/X-linkage). Hence, we describe in this study, for the first time, Y-linked genes in the R. prolixus genome: two zinc finger proteins (Znf-Y1 and Znf-Y2), one metalloproteinase (Met-Y), one aconitase/iron regulatory protein (Aco-Y) and five genes devoid of matches in any database (Rpr-Y1 to Rpr-Y5). Expression profile studies revealed that eight genes are expressed mainly in adult testis (some of which presented a weak expression in the initial developmental stages), while Aco-Y has a gut-restricted expression. CONCLUSIONS: In this study we showed that the approach used for the R. prolixus genome project (separate sequencing of male and female DNA) is key to easy and fast identification of sex-specific (e.g. Y chromosome sequences). The nine new R. prolixus Y-linked genes reported here provide unique markers for population and phylogenetic analysis and further functional studies of these genes may answer some questions about sex determination, male fertility and Y chromosome evolution in this important species. PMID- 26861772 TI - High content screening application for cell-type specific behaviour in heterogeneous primary breast epithelial subpopulations. AB - BACKGROUND: The complex interaction between multiple cell types and the microenvironment underlies the diverse pathways to carcinogenesis and necessitates sophisticated approaches to in vitro hypotheses testing. The combination of mixed culture format with high content immunofluorescence screening technology provides a powerful platform for observation of cell type specific behavior. METHODS: We have developed a versatile, high-throughput method for assessing cell-type specific responses. In addition to the specificity and sensitivity offered traditionally by immunofluorescent detection in flow cytometry, the 'in-cell' analysis method we describe provides the added benefits of higher throughput and the ability to analyse protein subcellular localisation in situ. Furthermore, elimination of the cell dissociation step allows for more immediate analysis of responses to specific extrinsic stimuli. We applied this method to investigate ionising radiation treatment response in normal breast epithelial cells, measuring growth rate, cell cycle response and double-strand DNA breaks. RESULTS: The 'in-cell' analysis approach elucidated several interesting donor and cell-type specific differences. Notably, in response to ionizing radiation we observed differential expression in luminal and basal-like cells of a member of the APOBEC enzyme family, recently identified as a critical driver of an oncogenic signature. Our findings suggest that this enzyme is active in the normal breast epithelium during DNA damage response. CONCLUSIONS: We demonstrate the practical application of a new method for assessing cell-type specific change in mixed cultures, especially the analysis of normal primary cultures, overcoming a major technical issue of dissecting the response of multiple cell types in a heterogeneous population. PMID- 26861773 TI - Plant responses to ambient temperature fluctuations and water-limiting conditions: A proteome-wide perspective. AB - BACKGROUND: Every year, environmental stresses such as limited water and nutrient availability, salinity, and temperature fluctuations inflict significant losses on crop yields across the globe. Recently, developments in analytical techniques, e.g. mass spectrometry, have led to great advances towards understanding how plants respond to environmental stresses. These processes are mediated by many molecular pathways and, at least partially, via proteome-environment interactions. SCOPE OF REVIEW: This review focuses on the current state of knowledge about interactions between the plant proteome and the environment, with a special focus on drought and temperature responses of plant proteome dynamics, and subcellular and organ-specific compartmentalization, in Arabidopsis thaliana and crop species. MAJOR CONCLUSIONS: Correct plant development under non-optimal conditions requires complex self-protection mechanisms, many of them common to different abiotic stresses. Proteome analyses of plant responses to temperature and drought stresses have revealed an intriguing interplay of modifications, mainly affecting the photosynthetic machinery, carbohydrate metabolism, and ROS activation and scavenging. Imbalances between transcript-level and protein-level regulation observed during adaptation to abiotic stresses suggest that many of the regulatory processes are controlled at translational and post-translational levels; proteomics is thus essential in revealing important regulatory networks. GENERAL SIGNIFICANCE: Because information from proteomic data extends far beyond what can be deduced from transcriptome analysis, the results of proteome studies have substantially deepened our understanding of stress adaptation in plants; this is clearly a prerequisite for designing strategies to improve the yield and quality of crops grown under unfavorable conditions brought about by ongoing climatic change. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. PMID- 26861774 TI - Protein S-nitrosylation in photosynthetic organisms: A comprehensive overview with future perspectives. AB - BACKGROUND: The free radical nitric oxide (NO) and derivative reactive nitrogen species (RNS) play essential roles in cellular redox regulation mainly through protein S-nitrosylation, a redox post-translational modification in which specific cysteines are converted to nitrosothiols. SCOPE OF VIEW: This review aims to discuss the current state of knowledge, as well as future perspectives, regarding protein S-nitrosylation in photosynthetic organisms. MAJOR CONCLUSIONS: NO, synthesized by plants from different sources (nitrite, arginine), provides directly or indirectly the nitroso moiety of nitrosothiols. Biosynthesis, reactivity and scavenging systems of NO/RNS, determine the NO-based signaling including the rate of protein nitrosylation. Denitrosylation reactions compete with nitrosylation in setting the levels of nitrosylated proteins in vivo. GENERAL SIGNIFICANCE: Based on a combination of proteomic, biochemical and genetic approaches, protein nitrosylation is emerging as a pervasive player in cell signaling networks. Specificity of protein nitrosylation and integration among different post-translational modifications are among the major challenges for future experimental studies in the redox biology field. This article is part of a Special Issue entitled: Plant Proteomics--a bridge between fundamental processes and crop production, edited by Dr. Hans-Peter Mock. PMID- 26861775 TI - Content and quality - integrated, holistic, one-stop antenatal care is needed for all. PMID- 26861776 TI - GABA: Inhibition brings new excitement in Parkinson's disease. PMID- 26861777 TI - New effective chemically synthesized anti-smallpox compound NIOCH-14. AB - Antiviral activity of the new chemically synthesized compound NIOCH-14 (a derivative of tricyclodicarboxylic acid) in comparison with ST-246 (the condensed derivative of pyrroledione) was observed in experiments in vitro and in vivo using orthopoxviruses including highly pathogenic ones. After oral administration of NIOCH-14 to outbred ICR mice infected intranasally with 100 % lethal dose of ectromelia virus, it was shown that 50 % effective doses of NIOCH-14 and ST-246 did not significantly differ. The 'therapeutic window' varied from 1 day before infection to 6 days post-infection (p.i.) to achieve 100-60 % survival rate. The administration of NIOCH-14 and ST-246 to mice resulted in a significant reduction of ectromelia virus titres in organs examined as compared with the control and also reduced pathological changes in the lungs 6 days p.i. Oral administration of NIOCH-14 and ST-246 to ICR mice and marmots challenged with monkeypox virus as compared with the control resulted in a significant reduction of virus production in the lungs and the proportion of infected mice 7 days p.i. as well as the absence of disease in marmots. Significantly lower proportions of infected mice and virus production levels in the lungs as compared with the control were demonstrated in experiments after oral administration of NIOCH-14 and ST-246 to ICR mice and immunodeficient SCID mice challenged with variola virus 3 and 4 days p.i., respectively. The results obtained suggest good prospects for further study of the chemical compound NIOCH-14 to create a new smallpox drug on its basis. PMID- 26861778 TI - Sleep disordered breathing and cardiovascular risk in older patients initiating dialysis in the United States: a retrospective observational study using medicare data. AB - BACKGROUND: Sleep disordered breathing (SDB) such as sleep apnea is associated with cardiovascular disease in the general population. However, little is known about the cardiovascular risks of SDB in patients with end-stage renal disease (ESRD). METHODS: We identified Medicare fee-for-service beneficiaries aged >=67 years initiating dialysis between 2004 and 2009. Outcomes of interest included all-cause mortality, incident myocardial infarction, ischemic stroke, and atrial fibrillation. We compared patients with and without diagnosed SDB using Cox proportional hazards regression. RESULTS: Between 2004 and 2009, 184,217 older patients developed ESRD, of whom 15,121 (8.2 %) were previously diagnosed with SDB. Patients diagnosed with SDB were younger, more likely to be male and Caucasian, less Medicaid eligible, had more non-Nephrology clinic visits, higher body mass index, and more comorbidity. In analyses adjusting for demographics and BMI, diagnosed SDB was associated with higher risk of death and atrial fibrillation, but not associated with myocardial infarction or ischemic stroke risk. After further adjustment for all baseline characteristics, diagnosed SDB was associated with slightly lower risks of death (hazard ratio [HR]: 0.93, 95 % confidence interval [CI]: 0.91-0.96), myocardial infarction (HR: 0.92, CI: 0.87 0.98), and ischemic stroke (HR: 0.90, 95 % CI: 0.82-0.98), and not associated with atrial fibrillation (HR: 1.02, CI: 0.98-1.07). CONCLUSIONS: In older patients initiating dialysis in the U.S., diagnosed SDB was weakly associated with lower risks of death and important cardiovascular outcomes, thus adding to the list of established risk factors that are paradoxically associated with cardiovascular outcomes in the ESRD population. PMID- 26861780 TI - Widespread distribution of Plasmodium vivax malaria in Mauritania on the interface of the Maghreb and West Africa. AB - BACKGROUND: Plasmodium vivax is very rarely seen in West Africa, although specific detection methods are not widely applied in the region, and it is now considered to be absent from North Africa. However, this parasite species has recently been reported to account for most malaria cases in Nouakchott, the capital of Mauritania, which is a large country at the interface of sub-Saharan West Africa and the Maghreb region in northwest Africa. METHODS: To determine the distribution of malaria parasite species throughout Mauritania, malaria cases were sampled in 2012 and 2013 from health facilities in 12 different areas. These sampling sites were located in eight major administrative regions of the country, within different parts of the Sahara and Sahel zones. Blood spots from finger prick samples of malaria cases were processed to identify parasite DNA by species specific PCR. RESULTS: Out of 472 malaria cases examined, 163 (34.5 %) had P. vivax alone, 296 (62.7 %) Plasmodium falciparum alone, and 13 (2.8 %) had mixed P. falciparum and P. vivax infection. All cases were negative for Plasmodium malariae and Plasmodium ovale. The parasite species distribution showed a broad spectrum, P. vivax being detected at six of the different sites, in five of the country's major administrative regions (Tiris Zemmour, Tagant, Brakna, Assaba, and the capital Nouakchott). Most cases in Nouakchott were due to P. vivax, although proportions vary significantly among different health facilities in the city. In the northern town of Zouerat, all cases were due to P. vivax, whereas almost all cases in the south of the country were due to P. falciparum. All P. vivax cases tested were Duffy blood group positive. CONCLUSIONS: It is important that P. vivax is recognized to be a widespread cause of malaria in Mauritania, occurring in diverse regions. This should be noted by the World Health Organization, as it has significant implications for diagnosis, treatment and control of malaria in the northwestern part of Africa. PMID- 26861779 TI - Using animal models to overcome temporal, spatial and combinatorial challenges in HIV persistence research. AB - Research challenges associated with understanding HIV persistence during antiretroviral therapy can be categorized as temporal, spatial and combinatorial. Temporal research challenges relate to the timing of events during establishment and maintenance of HIV persistence. Spatial research challenges regard the anatomical locations and cell subsets that harbor persistent HIV. Combinatorial research challenges pertain to the order of administration, timing of administration and specific combinations of compounds to be administered during HIV eradication therapy. Overcoming these challenges will improve our understanding of HIV persistence and move the field closer to achieving eradication of persistent HIV. Given that humanized mice and non-human primate HIV models permit rigorous control of experimental conditions, these models have been used extensively as in vivo research platforms for directly addressing these research challenges. The aim of this manuscript is to provide a comprehensive review of these recent translational advances made in animal models of HIV persistence. PMID- 26861781 TI - Insulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain. AB - Hepatic steatosis is common in obesity and insulin resistance and results from a net retention of lipids in the liver. A key mechanism to prevent steatosis is to increase secretion of triglycerides (TG) packaged as VLDLs. Insulin controls nutrient partitioning via signaling through its cognate receptor in peripheral target organs such as liver, muscle, and adipose tissue and via signaling in the central nervous system (CNS) to orchestrate organ cross talk. While hepatic insulin signaling is known to suppress VLDL production from the liver, it is unknown whether brain insulin signaling independently regulates hepatic VLDL secretion. Here, we show that in conscious, unrestrained male Sprague Dawley rats the infusion of insulin into the third ventricle acutely increased hepatic TG secretion. Chronic infusion of insulin into the CNS via osmotic minipumps reduced the hepatic lipid content as assessed by noninvasive (1)H-MRS and lipid profiling independent of changes in hepatic de novo lipogenesis and food intake. In mice that lack the insulin receptor in the brain, hepatic TG secretion was reduced compared with wild-type littermate controls. These studies identify brain insulin as an important permissive factor in hepatic VLDL secretion that protects against hepatic steatosis. PMID- 26861782 TI - Metabolite Profiles of Diabetes Incidence and Intervention Response in the Diabetes Prevention Program. AB - Identifying novel biomarkers of type 2 diabetes risk may improve prediction and prevention among individuals at high risk of the disease and elucidate new biological pathways relevant to diabetes development. We performed plasma metabolite profiling in the Diabetes Prevention Program (DPP), a completed trial that randomized high-risk individuals to lifestyle, metformin, or placebo interventions. Previously reported markers, branched-chain and aromatic amino acids and glutamine/glutamate, were associated with incident diabetes (P < 0.05 for all), but these associations were attenuated upon adjustment for clinical and biochemical measures. By contrast, baseline levels of betaine, also known as glycine betaine (hazard ratio 0.84 per SD log metabolite level, P = 0.02), and three other metabolites were associated with incident diabetes even after adjustment. Moreover, betaine was increased by the lifestyle intervention, which was the most effective approach to preventing diabetes, and increases in betaine at 2 years were also associated with lower diabetes incidence (P = 0.01). Our findings indicate betaine is a marker of diabetes risk among high-risk individuals both at baseline and during preventive interventions and they complement animal models demonstrating a direct role for betaine in modulating metabolic health. PMID- 26861783 TI - Shift to Fatty Substrate Utilization in Response to Sodium-Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes. AB - Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release. In type 2 diabetes (T2D), along with decrements in plasma glucose and insulin levels and increments in glucagon release, sodium glucose cotransporter 2 (SGLT2) inhibitors induce stimulation of endogenous glucose production (EGP) and a suppression of tissue glucose disposal (TGD). We measured fasting and postmeal glucose fluxes in 25 subjects without diabetes using a double glucose tracer technique; in these subjects and in 66 previously reported patients with T2D, we also estimated lipolysis (from [(2)H5]glycerol turnover rate and circulating free fatty acids, glycerol, and triglycerides), lipid oxidation (LOx; by indirect calorimetry), and ketogenesis (from circulating beta-hydroxybutyrate concentrations). In both groups, empagliflozin administration raised EGP, lowered TGD, and stimulated lipolysis, LOx, and ketogenesis. The pattern of glycosuria-induced changes was similar in subjects without diabetes and in those with T2D but quantitatively smaller in the former. With chronic (4 weeks) versus acute (first dose) drug administration, glucose flux responses were attenuated, whereas lipid responses were enhanced; in patients with T2D, fasting beta-hydroxybutyrate levels rose from 246 +/- 288 to 561 +/- 596 umol/L (P < 0.01). We conclude that by shunting substantial amounts of carbohydrate into urine, SGLT2-mediated glycosuria results in a progressive shift in fuel utilization toward fatty substrates. The associated hormonal milieu (lower insulin-to-glucagon ratio) favors glucose release and ketogenesis. PMID- 26861784 TI - DNA Methylation and BMI: Investigating Identified Methylation Sites at HIF3A in a Causal Framework. AB - Multiple differentially methylated sites and regions associated with adiposity have now been identified in large-scale cross-sectional studies. We tested for replication of associations between previously identified CpG sites at HIF3A and adiposity in ~1,000 mother-offspring pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC). Availability of methylation and adiposity measures at multiple time points, as well as genetic data, allowed us to assess the temporal associations between adiposity and methylation and to make inferences regarding causality and directionality. Overall, our results were discordant with those expected if HIF3A methylation has a causal effect on BMI and provided more evidence for causality in the reverse direction (i.e., an effect of BMI on HIF3A methylation). These results are based on robust evidence from longitudinal analyses and were also partially supported by Mendelian randomization analysis, although this latter analysis was underpowered to detect a causal effect of BMI on HIF3A methylation. Our results also highlight an apparent long-lasting intergenerational influence of maternal BMI on offspring methylation at this locus, which may confound associations between own adiposity and HIF3A methylation. Further work is required to replicate and uncover the mechanisms underlying the direct and intergenerational effect of adiposity on DNA methylation. PMID- 26861785 TI - Disallowance of Acot7 in beta-Cells Is Required for Normal Glucose Tolerance and Insulin Secretion. AB - Encoding acyl-CoA thioesterase-7 (Acot7) is one of ~60 genes expressed ubiquitously across tissues but relatively silenced, or disallowed, in pancreatic beta-cells. The capacity of ACOT7 to hydrolyze long-chain acyl-CoA esters suggests potential roles in beta-oxidation, lipid biosynthesis, signal transduction, or insulin exocytosis. We explored the physiological relevance of beta-cell-specific Acot7 silencing by re-expressing ACOT7 in these cells. ACOT7 overexpression in clonal MIN6 and INS1(832/13) beta-cells impaired insulin secretion in response to glucose plus fatty acids. Furthermore, in a panel of transgenic mouse lines, we demonstrate that overexpression of mitochondrial ACOT7 selectively in the adult beta-cell reduces glucose tolerance dose dependently and impairs glucose-stimulated insulin secretion. By contrast, depolarization-induced secretion was unaffected, arguing against a direct action on the exocytotic machinery. Acyl-CoA levels, ATP/ADP increases, membrane depolarization, and Ca(2+) fluxes were all markedly reduced in transgenic mouse islets, whereas glucose-induced oxygen consumption was unchanged. Although glucose-induced increases in ATP/ADP ratio were similarly lowered after ACOT7 overexpression in INS1(832/13) cells, changes in mitochondrial membrane potential were unaffected, consistent with an action of Acot7 to increase cellular ATP consumption. Because Acot7 mRNA levels are increased in human islets in type 2 diabetes, inhibition of the enzyme might provide a novel therapeutic strategy. PMID- 26861786 TI - Maternal Glucose and Fatty Acid Kinetics and Infant Birth Weight in Obese Women With Type 2 Diabetes. AB - The objectives of this study were 1) to describe maternal glucose and lipid kinetics and 2) to examine the relationships with infant birth weight in obese women with pregestational type 2 diabetes during late pregnancy. Using stable isotope tracer methodology and mass spectrometry, maternal glucose and lipid kinetic rates during the basal condition were compared in three groups: lean women without diabetes (Lean, n = 25), obese women without diabetes (OB, n = 26), and obese women with pregestational type 2 diabetes (OB+DM, n = 28; total n = 79). Glucose and lipid kinetics during hyperinsulinemia were also measured in a subset of participants (n = 56). Relationships between maternal glucose and lipid kinetics during both conditions and infant birth weight were examined. Maternal endogenous glucose production (EGP) rate was higher in OB+DM than OB and Lean during hyperinsulinemia. Maternal insulin value at 50% palmitate Ra suppression (IC50) for palmitate suppression with insulinemia was higher in OB+DM than OB and Lean. Maternal EGP per unit insulin and plasma free fatty acid concentration during hyperinsulinemia most strongly predicted infant birth weight. Our findings suggest maternal fatty acid and glucose kinetics are altered during late pregnancy and might suggest a mechanism for higher birth weight in obese women with pregestational diabetes. PMID- 26861789 TI - How the oxygen tolerance of a [NiFe]-hydrogenase depends on quaternary structure. AB - 'Oxygen-tolerant' [NiFe]-hydrogenases can catalyze H2 oxidation under aerobic conditions, avoiding oxygenation and destruction of the active site. In one mechanism accounting for this special property, membrane-bound [NiFe] hydrogenases accommodate a pool of electrons that allows an O2 molecule attacking the active site to be converted rapidly to harmless water. An important advantage may stem from having a dimeric or higher-order quaternary structure in which the electron-transfer relay chain of one partner is electronically coupled to that in the other. Hydrogenase-1 from E. coli has a dimeric structure in which the distal [4Fe-4S] clusters in each monomer are located approximately 12 A apart, a distance conducive to fast electron tunneling. Such an arrangement can ensure that electrons from H2 oxidation released at the active site of one partner are immediately transferred to its counterpart when an O2 molecule attacks. This paper addresses the role of long-range, inter-domain electron transfer in the mechanism of O2-tolerance by comparing the properties of monomeric and dimeric forms of Hydrogenase-1. The results reveal a further interesting advantage that quaternary structure affords to proteins. PMID- 26861788 TI - Impaired nuclear factor erythroid 2-related factor 2 expression increases apoptosis of airway epithelial cells in patients with chronic obstructive pulmonary disease due to cigarette smoking. AB - BACKGROUND: Cigarette smoking-induced oxidative stress is known to be a key mechanism in COPD pathogenesis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a central transcription factor that regulates the antioxidant defense system. The aim of this study was to compare Nrf2 expression in COPD subjects and control subjects, and to determine the role of Nrf2 in protecting against oxidative stress-induced apoptosis. METHODS: We enrolled 8 COPD subjects and 7 control subjects in this study. We performed bronchial brushing by bronchoscopy and obtained bronchial epithelial cells from the airways. Nrf2 expression in bronchial epithelial cells was evaluated by real-time PCR and Western blotting. We examined the effect of 10 or 15 % cigarette smoke extract (CSE) induced A549 cells apoptosis using a time-lapse cell imaging assay with caspase-3/7 activation detecting reagent and performed Terminal deoxynucleotidyltransferase-mediated dUTP nick end labelling assay for confirming A549 cells apoptosis. We also examined the effects of Nrf2 knockdown and, 0.1, 0.5, and 1.0 mM N-acetyl cysteine on CSE-induced apoptosis. Statistical analyses were performed using t test, paired t-test or an analysis of variance followed by the Tukey-Kramer method. RESULTS: Nrf2 mRNA expression in COPD subjects was significantly lower than that in control subjects and Nrf2 mRNA were negatively correlated with pack year. Nrf2 protein in COPD subjects was significantly lower than that in control subjects. CSE-induced A549 cells apoptosis was increased in a time-, concentration-dependent manner, and was significantly increased by Nrf2 knockdown. N-acetyl cysteine significantly ameliorated CSE-induced apoptosis. CONCLUSIONS: Nrf2 expression was lower in COPD patients than in control subjects. Nrf2 might have a protective role against apoptosis caused by CSE-induced oxidative stress. These results suggest an involvement of Nrf2 in COPD and administration of antioxidants to patients with COPD might be a basic therapeutic option. PMID- 26861787 TI - Identification of miRNAs and Their Targets in the Liverwort Marchantia polymorpha by Integrating RNA-Seq and Degradome Analyses. AB - Bryophytes (liverworts, hornworts and mosses) comprise the three earliest diverging lineages of land plants (embryophytes). Marchantia polymorpha, a complex thalloid Marchantiopsida liverwort that has been developed into a model genetic system, occupies a key phylogenetic position. Therefore, M. polymorpha is useful in studies aiming to elucidate the evolution of gene regulation mechanisms in plants. In this study, we used computational, transcriptomic, small RNA and degradome analyses to characterize microRNA (miRNA)-mediated pathways of gene regulation in M. polymorpha. The data have been integrated into the open access ContigViews-miRNA platform for further reference. In addition to core components of the miRNA pathway, 129 unique miRNA sequences, 11 of which could be classified into seven miRNA families that are conserved in embryophytes (miR166a, miR390, miR529c, miR171-3p, miR408a, miR160 and miR319a), were identified. A combination of computational and degradome analyses allowed us to identify and experimentally validate 249 targets. In some cases, the target genes are orthologous to those of other embryophytes, but in other cases, the conserved miRNAs target either paralogs or members of different gene families. In addition, the newly discovered Mpo-miR11707.1 and Mpo-miR11707.2 are generated from a common precursor and target MpARGONAUTE1 (LW1759). Two other newly discovered miRNAs, Mpo-miR11687.1 and Mpo-miR11681.1, target the MADS-box transcription factors MpMADS1 and MpMADS2, respectively. Interestingly, one of the pentatricopeptide repeat (PPR) gene family members, MpPPR_66 (LW9825), the protein products of which are generally involved in various steps of RNA metabolism, has a long stem-loop transcript that can generate Mpo-miR11692.1 to autoregulate MpPPR_66 (LW9825) mRNA. This study provides a foundation for further investigations of the RNA mediated silencing mechanism in M. polymorpha as well as of the evolution of this gene silencing pathway in embryophytes. PMID- 26861791 TI - Overexpression of microRNA-210 promotes chondrocyte proliferation and extracellular matrix deposition by targeting HIF-3alpha in osteoarthritis. AB - The present study aimed to determine the effect of microRNA (miR)-210 on osteoarthritis (OA). The expression levels of miR-210, type I and X collagen (COL1A1 and COL10A1) and matrix metallopeptidase 13 (MMP13) in OA and normal chondrocytes were determined using reverse transcription-quantitative polymerase chain reaction analysis. The OA chondrocytes were transfected with an miRNA precursor for miR-210 or a negative control. After 3, 7, 14 and 21 days, the expression levels of miR-210 were examined, the proliferation of the OA chondrocytes were determined using an XTT assay and the protein levels of Ki67 and HIF-3alpha were analyzed by Western blotting. After 21 days, the mRNA and protein levels of COL1A1, COL10A1 and MMP13 were analyzed. Th present study demonstrated that the expression levels of miR-210 and COL1A1 were lower, and the expression levels of COL10A1 and MMP13 were higher in the OA chondrocytes, compared with the levels of expression in the normal chondrocytes. Overexpression of miR-210 significantly promoted the proliferation of OA chondrocytes and induced the protein expression of Ki67. In addition, miR-210 overexpression markedly increased the expression of COL1A1 expression, but decreased the expression levels of COL10A1 and MMP13. A luciferase reporter assay confirmed the direct interaction between miR-210 and hypoxia-inducible factor (HIF)-3alpha. miR 210 did not alter the mRNA expression of HIF-3alpha, however, it suppressed the protein expression of HIF-3alpha. Additionally, HIF-3alpha knockdown significantly promoted OA chondrocyte proliferation and increased the mRNA levels of COL1A1, whereas it decreased the mRNA levels of COL10A1 and MMP13. The results of the present study suggested that miR-210 may be a negative regulator of the progression of OA, which increases chondrocyte proliferation and prompts extracellular matrix deposition by directly targeting HIF-3alpha. PMID- 26861792 TI - Five minutes with . . . Nigel Crisp. PMID- 26861790 TI - [Hierarchical assessment of balance and mobility : German translation and cross cultural adaptation]. AB - BACKGROUND: The hierarchical assessment of balance and mobility (HABAM) is an internationally established clinical mobility test which has good psychometric properties, allows an easy assessment of mobility and the graphical illustration of change over time in geriatric patients. The aims of this study were the translation and cross-cultural adaptation of the English original HABAM into the German language as well as a preliminary analysis of the practicability and construct validity of the HABAM. MATERIAL AND METHODS: The HABAM was translated into German following international guidelines. A prefinal version was clinically tested by physiotherapists in two geriatric hospitals over a period of 5 weeks. In order to make a final revision of the German HABAM version, structured in depth feedback was obtained from the seven therapists who had used the HABAM most often. RESULTS: A total of 18 physiotherapists used the HABAM for 47 elderly inpatients for the initial assessment. The translated items and instructions seemed comprehensible but problems occurred concerning the conducting and documentation of the HABAM. Modifications led to the final German HABAM version and 85 % of the HABAM assessments were performed within <= 10 min. There was a correlation of rs= 0.71 with the Tinetti test and of rs = 0.68 with the Barthel index. CONCLUSION: A German HABAM version is now accessible for use in clinical practice. The results of a preliminary psychometric analysis indicate a potentially good practicability and sufficient construct validity. A comprehensive analysis of psychometric properties is pending. PMID- 26861793 TI - Identification of Evidence for Key Parameters in Decision-Analytic Models of Cost Effectiveness: A Description of Sources and a Recommended Minimum Search Requirement. AB - This paper proposes recommendations for a minimum level of searching for data for key parameters in decision-analytic models of cost effectiveness and describes sources of evidence relevant to each parameter type. Key parameters are defined as treatment effects, adverse effects, costs, resource use, health state utility values (HSUVs) and baseline risk of events. The recommended minimum requirement for treatment effects is comprehensive searching according to available methodological guidance. For other parameter types, the minimum is the searching of one bibliographic database plus, where appropriate, specialist sources and non research-based and non-standard format sources. The recommendations draw on the search methods literature and on existing analyses of how evidence is used to support decision-analytic models. They take account of the range of research and non-research-based sources of evidence used in cost-effectiveness models and of the need for efficient searching. Consideration is given to what constitutes best evidence for the different parameter types in terms of design and scientific quality and to making transparent the judgments that underpin the selection of evidence from the options available. Methodological issues are discussed, including the differences between decision-analytic models of cost effectiveness and systematic reviews when searching and selecting evidence and comprehensive versus sufficient searching. Areas are highlighted where further methodological research is required. PMID- 26861794 TI - Promoting Dignity: The Ethical Dimension of Health. AB - The article examines the limitations of a strict scientific account of the causes of unhealthy behaviors, based on the standards promoted in evidence-based medicine, where randomized controlled trials are seen to provide the gold standard for establishing the validity of different explanations. The article critiques this account based on its disputed assumption that human free will does not exist, and thus, human autonomy and moral responsibility are an illusion. By denying human autonomy, the naturalistic paradigm also denies the possibility of human dignity. In contrast, the article describes and explains a humanistic account of human agency where human beings are characterized by the capacity to choose how to live their lives based on values that matter. Based on this humanistic framework, the article explains why dignity is an essential dimension of human health and well-being and describes key research challenges in moving the field of health promotion in a more humanistic direction. The article concludes with the recommendation to expand the goal of health promotion beyond physical fitness and to reorient the methods of research toward articulating values that matter and promoting human dignity. PMID- 26861795 TI - Discrimination and Depressive Symptoms Among Latina/o Adolescents of Immigrant Parents. AB - Discrimination is associated with negative mental health outcomes for Latina/o adolescents. While Latino/a adolescents experience discrimination from a number of sources and across contexts, little research considers how the source of discrimination and the context in which it occurs affect mental health outcomes among Latina/o children of immigrants. We examined the association between source specific discrimination, racial or ethnic background of the source, and school ethnic context with depressive symptoms for Latina/o adolescents of immigrant parents. Using multilevel linear regression with time-varying covariates, we regressed depressive symptoms on source-specific discrimination, racial or ethnic background of the source of discrimination, and school percent Latina/o. Discrimination from teachers (beta = 0.06, p < .05), students (beta = 0.05, p < .05), Cubans (beta = 0.19, p < .001), and Latinas/os (beta = 0.19, p < .001) were positively associated with depressive symptoms. These associations were not moderated by school percent Latina/o. The findings indicate a need to reduce discrimination to improve Latina/o adolescents' mental health. PMID- 26861796 TI - Drivers who self-estimate lower blood alcohol concentrations are riskier drivers after drinking. AB - RATIONALE: Alcohol increases the tendency for risky driving in some individuals but not others. Little is known about the factors underlying this individual difference. Studies find that those who underestimate their blood alcohol concentration (BAC) following a dose of alcohol tend to be more impulsive and report greater willingness to drive after drinking than those who estimate their BACs to be greater than their actual BAC. BAC underestimation could contribute to risky driving behavior following alcohol as such drivers might perceive little impairment in their driving ability and thus no need for caution. OBJECTIVES: This study was designed to test the relationship between drivers' BAC estimations following a dose of alcohol or a placebo and the degree of risky driving they displayed during a simulated driving test. METHODS: Forty adult drivers performed a simulated driving test and estimated their blood alcohol concentration after receiving a dose of alcohol (0.65 g/kg for men and 0.56 g/kg for women) or a placebo. RESULTS: Alcohol increased risk-taking and impaired driving skill. Those who estimated their BAC to be lower were the riskiest drivers following both alcohol and placebo. CONCLUSIONS: The tendency to estimate lower BACs could support a series of high-risk decisions, regardless of one's actual BAC. This could include the decision to drive after drinking. PMID- 26861798 TI - Pelvic X-ray misses out on detecting sacral fractures in the elderly - Importance of CT imaging in blunt pelvic trauma. AB - Patients aged 75 years and older with blunt pelvic trauma are frequently seen in the ER. The standard diagnostic tool in these patients is the plain a.p. radiograph of the pelvis. Especially lesions of the posterior pelvic ring are often missed due to e.g. bowel gas projection and enteric overlay. With a retrospective study covering these patients over a 3 year period in our level I trauma centre, we were able to evaluate the rate of missed injuries in the a.p. radiograph whenever a corresponding CT scan was performed. Age, gender, and accompanying fractures of the pelvic ring were recorded. The intrinsic test characteristics and the performance in the population were calculated according to standard formulas. Thus, 233 consecutive patients with blunt pelvic trauma with both conventional radiographic examination and computed tomography (CT) were included. Thereof, 56 (23%) showed a sacral fracture in the CT scan. Of 233 pelvic X-ray-images taken, 227 showed no sacral fracture. 51 (21.7%) of these were false negative, yielding a sensitivity of just 10.5%. Average age of patients with sacral fractures was 85.1+/-6.1 years, with 88% being female. Sacral fractures were often accompanied by lesions of the anterior pelvic ring with pubic bone fractures in 75% of sacrum fracture cases. Second most concomitant fractures are found at the acetabulum (23.3%). Plain radiographic imaging is especially likely to miss out fractures of the posterior pelvic ring, which nowadays can be of therapeutic consequence. Besides the physicians experience in the ED, profound knowledge of insensitivity of plain radiographs in finding posterior pelvic ring lesions is crucial for a reliable diagnostic routine. Since the high mortality caused by prolonged immobilisation due to pelvic ring injuries, all fractures should be identified. We therefore provide a diagnostic algorithm for blunt pelvic trauma in the elderly. PMID- 26861799 TI - Surgical exposures and options for instrumentation in acetabular fracture fixation: Pararectus approach versus the modified Stoppa. AB - BACKGROUND: As an alternative to the modified Stoppa approach, the Pararectus approach is used clinically for treatment of acetabular fractures involving the anterior column. The current study assessed the surgical exposure and the options for instrumentation using both of these approaches. METHODS: Surgical dissections were conducted on five human cadavers (all male, mean age 88 years (82-97)) using the modified Stoppa and the Pararectus approach, with the same skin incision length (10cm). Distal boundaries of the exposed bony surfaces were marked using a chisel. After removal of all soft-tissues, distances from the boundaries in the false and true pelvis were measured with reference to the pelvic brim. The exposed bone was coloured and calibrated digital images of each inner hemipelvis were taken. The amount of exposed surface using both approaches was assessed and represented as a percentage of the total bony surface of each hemipelvis. For instrumentation, a suprapectineal quadrilateral buttress plate was used. Screw lengths were documented, and three-dimensional CT reconstructions were performed to assess screw trajectories qualitatively. Wilcoxon's signed rank test for paired groups was used (level of significance: p<0.05). RESULTS: After utilization of the Pararectus approach, the distances from the farthest boundaries of exposed bone towards the pelvic brim were significantly higher in the false but not the true pelvis, compared to the modified Stoppa approach. The percentage (mean+/-SD) of exposed bone accessible after utilizing the Pararectus approach was 42+/-8%, compared to 29+/-6% using the modified Stoppa (p=0.011). In cadavers exposed by the Pararectus approach, screws placed for posterior fixation and as a posterior column screw were longer by factor 1.8 and 2.1, respectively (p<0.05), and screws could be placed more posteromedial towards the posterior inferior iliac spine or in line with the posterior column directed towards the ischial tuberosity. CONCLUSION: Compared to the modified Stoppa, the Pararectus approach facilitates a greater surgical access in the false pelvis, provides versatility for fracture fixation in the posterior pelvic ring and allows for the option to extend the approach without a new incision. PMID- 26861797 TI - Regulating task-monitoring systems in response to variable reward contingencies and outcomes in cocaine addicts. AB - BACKGROUND: We investigated anticipatory and consummatory reward processing in cocaine addiction. In addition, we set out to assess whether task-monitoring systems were appropriately recalibrated in light of variable reward schedules. We also examined neural measures of task-monitoring and reward processing as a function of hedonic tone, since anhedonia is a vulnerability marker for addiction that is obviously germane in the context of reward processing. METHOD: High density event-related potentials were recorded while participants performed a speeded response task that systematically varied anticipated probabilities of reward receipt. The paradigm dissociated feedback regarding task success (or failure) from feedback regarding the value of reward (or loss), so that task monitoring and reward processing could be examined in partial isolation. Twenty three active cocaine abusers and 23 age-matched healthy controls participated. RESULTS: Cocaine abusers showed amplified anticipatory responses to reward predictive cues, but crucially, these responses were not as strongly modulated by reward probability as in controls. Cocaine users also showed blunted responses to feedback about task success or failure and did not use this information to update predictions about reward. In turn, they showed clearly blunted responses to reward feedback. In controls and users, measures of anhedonia were associated with reward motivation. In cocaine users, anhedonia was also associated with diminished monitoring and reward feedback responses. CONCLUSION: Findings imply that reward anticipation and monitoring deficiencies in addiction are associated with increased responsiveness to reward cues but impaired ability to predict reward in light of task contingencies, compounded by deficits in responding to actual reward outcomes. PMID- 26861800 TI - Endoscopic treatment of Morel-Lavallee lesion. AB - Morel-Lavallee lesion is a closed degloving soft tissue injury in which subcutaneous tissue is torn from the underlying muscular fascia. The tear leads to venolymphatic leak, and concomitant adipose tissue necrosis from the force of the trauma causes swelling and possible infection at the site of injury. The traditional treatment for the lesion is surgical drainage and debridement. In this report, an endoscopic method is described, which achieves the goal of an open surgical debridement but minimizes surgical morbidity. PMID- 26861801 TI - Variation in patterns of hospitalization and associated resource use among children with spinal cord injury in the U.S. AB - INTRODUCTION: Trauma is a leading cause of mortality and morbidity among children in the U.S. There is paucity of data on the triage of children with spinal cord injury (SCI) to definitive trauma care, and it is unknown if clinical outcomes and resource utilization for children hospitalized with SCI vary according to the settings where trauma care is provided. The study was conducted to describe recent patterns of emergency department (ED) evaluation for paediatric SCI in the U.S., and to characterize outcomes and resource use for children hospitalized at non-trauma centres versus trauma centres. MATERIALS AND METHODS: Secondary analysis of a national database on injured children 0-20 years evaluated at U.S. EDs and either hospitalized or released, in 2009-2012. In-hospital mortality, duration of stay, and overall charges, were compared according to trauma centre status of the treating hospital. RESULTS: Of an estimated 67 million annual paediatric visits to the ED for trauma evaluation nationally in 2009-2012, 2317 had SCI. Majority (87%) of children evaluated for SCI were under 6 years of age, and boys comprised 73% of the visits. Injuries were caused mainly by motor vehicle accidents, falls, non-transport-related accidents, and firearms. The South census region had the most ED visits and hospitalizations. Majority (92%) of the most severely injured was evaluated at trauma centres, and more visits to trauma centres (81% vs. 18%, p=0.022) resulted in hospitalization. Among an estimated 1570 hospitalizations of children with SCI from the ED nationally, children at trauma centres were more likely to have major injuries (67% vs. 44%, p=0.001), similar mortality, longer average hospital stay, and higher charges, compared with children hospitalized at non-trauma centres. CONCLUSION: Significant demographic and geographical variation exists in national patterns of hospital care for paediatric SCI. Higher severity of patient injury was associated with concomitantly higher hospital resource use at trauma centres. PMID- 26861802 TI - Acute ischemia and pink pulseless hand in 68 of 404 gartland type III supracondylar humeral fractures in children: Urgent management and therapeutic consensus. AB - No consensus exists regarding pulseless otherwise well-perfused hand in pediatric Gartland type III fractures. The purpose of this retrospective study was to describe our strategy and to determine the guidelines of therapeutic consensus. PATIENTS AND METHODS: 404 children were treated for a type III supracondylar humeral fracture. Extension fractures-induced acute vascular injuries were noticed in 68 patients and nerve injuries were associated in 32 of them. The radial pulse was absent in all patients with two clinical situations at the initial presentation: well-perfused hand with 'pink and warm' hand in 63 patients and ischemia with 'white and cold' hand in five. Urgent closed reduction of the fracture and stabilization were performed in 63 patients with pink pulseless hand, and immediate surgical exploration in the five patients with ischemia. RESULTS: 63 patients with vascular injury had posterolateral displacement and 5 had posteromedial displacement. Sixty-three of 68 patients had posterolateral displacement of whom 28 had concomitant median nerve injury and 4 had a deficit to both median and ulnar nerves. The palpable radial pulse was immediately restored in 42 patients and between few hours to eleven days later in eighteen. Three patients with ischemia after unsuccessful reduction required immediate surgical exploration revealing incarceration of the brachial artery at the fracture site. Release and decompression of the brachial artery restored a normal limb perfusion. The five patients with primary ischemia underwent immediate open exploration and vascular repair. One of them had a compartment syndrome and required anterior fasciotomy. The restoration of blood flow with palpable radial pulse was observed in all patients. Full spontaneous nerve recovery was observed in all patients. At an average follow-up of 8.4 years, all patients had normal circulatory status, including a palpable radial pulse. DISCUSSION: This study highlighted the reliability of non invasive strategy with good outcomes. We recommend urgent closed reduction of fracture. Close observation and monitoring is mandatory if pulseless hand remains warm and well-perfused. If the patients develop blood circulation disturbances or compartment syndrome following closed reduction, immediate vascular exploration is recommend. PMID- 26861803 TI - Computing the stresses and deformations of the human eye components due to a high explosive detonation using fluid-structure interaction model. AB - INTRODUCTION: In spite the fact that a very small human body surface area is comprised by the eye, its wounds due to detonation have recently been dramatically amplified. Although many efforts have been devoted to measure injury of the globe, there is still a lack of knowledge on the injury mechanism due to Primary Blast Wave (PBW). The goal of this study was to determine the stresses and deformations of the human eye components, including the cornea, aqueous, iris, ciliary body, lens, vitreous, retina, sclera, optic nerve, and muscles, attributed to PBW induced by trinitrotoluene (TNT) explosion via a Lagrangian Eulerian computational coupling model. MATERIALS AND METHODS: Magnetic Resonance Imaging (MRI) was employed to establish a Finite Element (FE) model of the human eye according to a normal human eye. The solid components of the eye were modelled as Lagrangian mesh, while an explosive TNT, air domain, and aqueous were modelled using Arbitrary Lagrangian-Eulerian (ALE) mesh. Nonlinear dynamic FE simulations were accomplished using the explicit FE code, namely LS-DYNA. In order to simulate the blast wave generation, propagation, and interaction with the eye, the ALE formulation with Jones-Wilkins-Lee (JWL) equation defining the explosive material were employed. RESULTS: The results revealed a peak stress of 135.70kPa brought about by detonation upsurge on the cornea at the distance of 25cm. The highest von Mises stresses were observed on the sclera (267.3kPa), whereas the lowest one was seen on the vitreous body (0.002kPa). The results also showed a relatively high resultant displacement for the macula as well as a high variation for the radius of curvature for the cornea and lens, which can result in both macular holes, optic nerve damage and, consequently, vision loss. CONCLUSION: These results may have implications not only for understanding the value of stresses and strains in the human eye components but also giving an outlook about the process of PBW triggers damage to the eye. PMID- 26861804 TI - How breast cancer chemotherapy increases the risk of leukemia: Thoughts about a case of diffuse large B-cell lymphoma and leukemia after breast cancer chemotherapy. AB - The latest studies suggest that prophylactic chemotherapy or adjuvant chemotherapy for early stage breast cancer may increase the leukemia risk in patients. For patients with a low risk for breast cancer recurrence, physicians who make the choice for adjuvant therapy should consider the risk of its long term side effects. Is the occurrence of lymphatic system cancer and leukemia after breast cancer treatment associated with chemotherapy? Can these types of leukemia be classified as therapy-related leukaemias? We believe that there may be correlations between any diseases, butwe cannot rush to conclusions or dismiss a correlation because we understand little about the diseases themselves.In this paper, we present a case of secondary diffuse large B-cell lymphoma and leukemia in patients after breast cancer chemotherapy, it is undeniable that this is a special event. For two distinct tumouroccurrences at different times, we cannot give a clear explanation because of thechanges in the genes that might link them together and we hope to attract the attention of other clinicians. PMID- 26861805 TI - Room-Temperature, Near-Instantaneous Fabrication of Auxetic Materials with Constant Poisson's Ratio over Large Deformation. AB - A novel compressed carbon dioxide assisted fabrication method is demonstrated to produce auxetic PU foam. Auxetic PU foams can be fabricated at room temperature (25 degrees C) in several seconds with compressed CO2. This technology overcomes some key challenging issues in the large-scale production of auxetic PU foams. PMID- 26861806 TI - Editorial: Chemistry Towards Biology: Proceedings of the Katowice Conference. PMID- 26861807 TI - Advances in the Classification and Treatment of Osteogenesis Imperfecta. AB - Osteogenesis imperfecta (OI) is a rare disorder of type 1 collagen with 13 currently identified types attributable to inherited abnormalities in type 1 collagen amount, structure, or processing. The disease is characterized by an increased susceptibility to bony fracture. In addition to the skeletal phenotype, common additional extraskeletal manifestations include blue sclerae, dentinogenesis imperfecta, vascular fragility, and hearing loss. Medical management is focused on minimizing the morbidity of fractures, pain, and bone deformities by maximizing bone health. Along with optimizing Vitamin D status and calcium intake and physical/occupational therapy, individualized surgical treatment may be indicated. Pharmacological therapy with bisphosphonate medications is now routinely utilized for moderate to severe forms and appears to have a good safety profile and bone health benefits. New therapies with other anti-resorptives as well as anabolic agents and transforming growth factor (TGF)beta antibodies are in development. Other potential treatment modalities could include gene therapy or mesenchymal cell transplant. In the future, treatment choices will be further individualized in order to reduce disease morbidity and mortality. PMID- 26861808 TI - How Mandated College Students Talk About Alcohol: Peer Communication Factors Associated with Drinking. AB - Relatively little research has examined how peer communication influences alcohol consumption. In a sample of mandated college students, we differentiate conversations about drinking from conversations about harm prevention and provide evidence for the validity of these communication constructs. Students who violated campus alcohol policies and were referred for alcohol sanctions (N = 345) reported on drinking patterns, use of protective behavioral strategies, perceived descriptive norms for close friends, and serving as social leader among their friends; they also reported on the frequency of conversations about drinking, about drinking safety, and about risk reduction efforts. Predicted correlations were found among types of communication and conceptually related variables. General communication was related to consumption but not protective behavioral strategies, whereas safety/risk reduction conversations correlated positively with all protective behavioral strategies. Both types of communication were associated with social leadership. Safety communication moderated the relationship between peer descriptive norms and drinks per week; more frequent talking about safety attenuated the norms-consumption relationship. Peer communication about both drinking and safety may serve as targets for change in risk reduction interventions for mandated college students. PMID- 26861810 TI - Application of Indirect Comparison to the Drug Development Process: Forecasting Direct Comparison Study Results. PMID- 26861809 TI - Identification of Entamoeba polecki with Unique 18S rRNA Gene Sequences from Celebes Crested Macaques and Pigs in Tangkoko Nature Reserve, North Sulawesi, Indonesia. AB - Unique species of macaques are distributed across Sulawesi Island, Indonesia, and the details of Entamoeba infections in these macaques are unknown. A total of 77 stool samples from Celebes crested macaques (Macaca nigra) and 14 stool samples from pigs were collected in Tangkoko Nature Reserve, North Sulawesi, and the prevalence of Entamoeba infection was examined by PCR. Entamoeba polecki was detected in 97% of the macaques and all of the pigs, but no other Entamoeba species were found. The nucleotide sequence of the 18S rRNA gene in E. polecki from M. nigra was unique and showed highest similarity with E. polecki subtype (ST) 4. This is the first case of identification of E. polecki ST4 from wild nonhuman primates. The sequence of the 18S rRNA gene in E. polecki from pigs was also unique and showed highest similarity with E. polecki ST1. These results suggest that the diversity of the 18S rRNA gene in E. polecki is associated with differences in host species and geographic localization, and that there has been no transmission of E. polecki between macaques and pigs in the study area. PMID- 26861812 TI - Biomechanical comparison of four sliding knots and three high-strength sutures: Loop security is much different between each combination. AB - There are many types of sliding knots and suture materials used in arthroscopic surgery. The purposes of this study are (i) to evaluate the loop security of standard sliding knots when using different types of high-strength suture materials and (ii) to compare the loop security of a new sliding knot (Chula knot) to other standard sliding knots. Four configurations of sliding locking knots (Weston, SMC, Tennessee and Chula knots) were tied using three commonly used suture materials: MagnumWire, Hi-Fi, and FiberWire. The suture loops were mounted on two metallic hooks of the universal testing machine. Then, the suture loop was pulled apart until failure. The Weston knot demonstrated the greatest load to failure in all suture materials. By using MagnumWire, the load to failure was as follow: Weston 53.2 N, Chula 48.8 N, SMC 39.2 N, and Tennessee 29.3 N. By using Hi-Fi, the load to failure was as follow: Weston 58.8 N, Chula 51.5 N, SMC 38.1 N, and Tennessee 28.7 N. By using FiberWire, the load to failure was as follow: Weston 38.8 N, Chula 29.7 N, SMC 23.2 N, and Tennessee 21.9 N. Weston knot has the highest loop security in all suture materials. Weston-HiFi combination demonstrate the strongest loop security. Conversely, the weakest combination is Tennessee-FiberWire. Chula knot has similar properties to other commonly used arthroscopic sliding knots. Our findings indicate that surgeons should be careful in selecting proper knot-suture combinations. (c) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1804-1807, 2016. PMID- 26861811 TI - Early Treatment with Basal Insulin Glargine in People with Type 2 Diabetes: Lessons from ORIGIN and Other Cardiovascular Trials. AB - Dysglycemia results from a deficit in first-phase insulin secretion compounded by increased insulin insensitivity, exposing beta cells to chronic hyperglycemia and excessive glycemic variability. Initiation of intensive insulin therapy at diagnosis of type 2 diabetes mellitus (T2DM) to achieve normoglycemia has been shown to reverse glucotoxicity, resulting in recovery of residual beta-cell function. The United Kingdom Prospective Diabetes Study (UKPDS) 10-year post trial follow-up reported reductions in cardiovascular outcomes and all-cause mortality in persons with T2DM who initially received intensive glucose control compared with standard therapy. In the cardiovascular outcome trial, outcome reduction with an initial glargine intervention (ORIGIN), a neutral effect on cardiovascular disease was observed in the population comprising prediabetes and T2DM. Worsening of glycemic control was prevented over the 6.7 year treatment period, with few serious hypoglycemic episodes and only moderate weight gain, with a lesser need for dual or triple oral treatment versus standard care. Several other studies have also highlighted the benefits of early insulin initiation as first-line or add-on therapy to metformin. The decision to introduce basal insulin to metformin must, however be individualized based on a risk-benefit analysis. The landmark ORIGIN trial provides many lessons relating to the concept and application of early insulin therapy for the prevention and safe and effective induction and maintenance of glycemic control in type 2 diabetes. FUNDING: Sanofi. PMID- 26861814 TI - An infectious disease and pharmacokinetic perspective on oral antibiotic treatment of uncomplicated urinary tract infections due to multidrug-resistant Gram-negative uropathogens: the importance of urinary antibiotic concentrations and urinary pH. PMID- 26861813 TI - Altered profile of regulatory T cells and associated cytokines in mild and moderate dengue. AB - The pathogenesis of dengue is immune-mediated. Regulatory T cells suppress immune response and may contribute to better prognosis. The present study evaluates Tregs and cytokines in dengue patients in the context of disease severity, time of sampling and immune status. The cohort included 90 patients (51 mild, 39 moderate) and 27 healthy controls. Frequencies of Tregs, CD4(+)CD25(-)Foxp3(+) T cells and CD3(+), CD3(+)CD4(+) and CD3(+)CD8(+) T cells were enumerated by flow cytometry. Circulating levels of 15 cytokines/chemokines were measured using Luminex technology and mRNA levels of Foxp3, IL-10 and TGF-beta were assessed by real-time polymerase chain reaction (PCR). Significantly higher frequencies of Tregs were observed in mild cases, especially during post-defervescence. The difference between mild and moderate cases was more evident in secondary infections. Frequencies of T cells were higher in mild cases but during pre defervescence. On the other hand, the levels of IL-6, IL-7, IL-8, TNF-alpha and IL-10 were significantly higher in moderate cases. IL-6 and IL-8 levels correlated negatively with Treg frequencies during post-defervescence and in secondary infections. Higher levels of IL-10 and TGF-beta in moderate cases were not reflected by their corresponding mRNA levels. Platelet counts correlated positively with Treg frequencies and TGF-beta levels, and negatively with IL-10 levels. Higher Treg frequencies may favour a beneficial outcome in dengue. Higher cytokine levels may indirectly contribute to disease severity by exerting an inhibitory influence on Tregs. The dichotomy between mRNA and proteins levels for IL-10 and TGF-beta is suggestive of increased translational efficiency. PMID- 26861815 TI - Deletion of the WNK3-SPAK kinase complex in mice improves radiographic and clinical outcomes in malignant cerebral edema after ischemic stroke. AB - The WNK-SPAK kinase signaling pathway controls renal NaCl reabsorption and systemic blood pressure by regulating ion transporters and channels. A WNK3-SPAK complex is highly expressed in brain, but its function in this organ remains unclear. Here, we investigated the role of this kinase complex in brain edema and white matter injury after ischemic stroke. Wild-type, WNK3 knockout, and SPAK heterozygous or knockout mice underwent transient middle cerebral artery occlusion. One cohort of mice underwent magnetic resonance imaging. Ex-vivo brains three days post-ischemia were imaged by slice-selective spin-echo diffusion tensor imaging magnetic resonance imaging, after which the same brain tissues were subjected to immunofluorescence staining. A second cohort of mice underwent neurological deficit analysis up to 14 days post-transient middle cerebral artery occlusion. Relative to wild-type mice, WNK3 knockout, SPAK heterozygous, and SPAK knockout mice each exhibited a >50% reduction in infarct size and associated cerebral edema, significantly less demyelination, and improved neurological outcomes. We conclude that WNK3-SPAK signaling regulates brain swelling, gray matter injury, and demyelination after ischemic stroke, and that WNK3-SPAK inhibition has therapeutic potential for treating malignant cerebral edema in the setting of middle cerebral artery stroke. PMID- 26861816 TI - Region specific contribution of ASIC2 to acidosis-and ischemia-induced neuronal injury. AB - Acidosis in the brain plays a critical role in neuronal injury in neurological diseases, including brain ischemia. One key mediator of acidosis-induced neuronal injury is the acid-sensing ion channels (ASICs). Current literature has focused on ASIC1a when studying acid signaling. The importance of ASIC2, which is also widely expressed in the brain, has not been appreciated. We found here a region specific effect of ASIC2 on acid-mediated responses. Deleting ASIC2 reduced acid activated current in cortical and striatal neurons, but had no significant effect in cerebellar granule neurons. In addition, we demonstrated that ASIC2 was important for ASIC1a expression, and that ASIC2a but not 2b facilitated ASIC1a surface trafficking in the brain. Further, we showed that ASIC2 deletion attenuated acidosis/ischemia-induced neuronal injury in organotypic hippocampal slices but had no effect in organotypic cerebellar slices. Consistent with an injurious role of ASIC2, we showed that ASIC2 deletion significantly protected the mouse brain from ischemic damage in vivo. These data suggest a critical region-specific contribution of ASIC2 to neuronal injury and reveal an important functional difference between ASIC2a and 2b in the brain. PMID- 26861817 TI - Assessment of tumor oxygenation and its impact on treatment response in bevacizumab-treated recurrent glioblastoma. AB - Antiantiogenic therapy with bevacizumab in recurrent glioblastoma is currently understood to both reduce microvascular density and to prune abnormal tumor microvessels. Microvascular pruning and the resulting vascular normalization are hypothesized to reduce tumor hypoxia and increase supply of systemic therapy to the tumor; however, the underlying pathophysiological changes and their timing after treatment initiation remain controversial. Here, we use a novel dynamic susceptibility contrast MRI-based method, which allows simultaneous assessment of tumor net oxygenation changes reflected by the tumor metabolic rate of oxygen and vascular normalization represented by the capillary transit time heterogeneity. We find that capillary transit time heterogeneity, and hence the oxygen extraction fraction combine with the tumoral blood flow (cerebral blood flow) in such a way that the overall tumor oxygenation appears to be worsened despite vascular normalization. Accordingly, hazards for both progression and death are found elevated in patients with a greater reduction of tumor metabolic rate of oxygen in response to bevacizumab and patients with higher intratumoral tumor metabolic rate of oxygen at baseline. This implies that tumors with a higher degree of angiogenesis prior to bevacizumab-treatment retain a higher level of angiogenesis during therapy despite a greater antiangiogenic effect of bevacizumab, hinting at evasive mechanisms limiting bevacizumab efficacy in that a reversal of their biological behavior and relative prognosis does not occur. PMID- 26861818 TI - Central nervous system disease and genital disease in harbor porpoises (Phocoena phocoena) are associated with different herpesviruses. AB - Herpesvirus infection causes disease of variable severity in many species, including cetaceans. However, little is known about herpesvirus infection in harbor porpoises (Phocoena phocoena), despite being widespread in temperate coastal waters of the Northern Hemisphere. Therefore, we examined harbor porpoises that stranded alive in the Netherlands, Belgium, and Germany between 2000 and 2014 for herpesvirus infection and associated disease. Porpoises that died or had to be euthanized were autopsied, and samples were collected for virological and pathological analyses. We found one known herpesvirus (Phocoena phocoena herpesvirus type 1, PPHV-1)--a gammaherpesvirus--and two novel herpesviruses (PPHV-2 and PPHV-3)--both alphaherpesviruses--in these porpoises. A genital plaque, in which PPHV-1 was detected, occurred in 1% (1/117) of porpoises. The plaque was characterized by epithelial hyperplasia and intranuclear inclusion bodies that contained herpesvirus-like particles, and that stained positive by a PPHV-1-specific in situ hybridization test. PPHV-2 occurred in the brain of 2% (1/74) of porpoises. This infection was associated with lymphocytic encephalitis, characterized by neuronal necrosis and intranuclear inclusion bodies containing herpesvirus-like particles. PPHV-3 had a prevalence of 5% (4/74) in brain tissue, 5% (2/43) in blowhole swabs, and 2% (1/43) in genital swabs, but was not associated with disease. Phylogenetically, PPHV-1 was identical to a previously reported herpesvirus from a harbor porpoise, PPHV-2 showed closest identity with two herpesviruses from dolphins, and PPHV-3 showed closest identity with a cervid herpesvirus. In conclusion, harbor porpoises may be infected with at least three different herpesviruses, one of which can cause clinically severe neurological disease. PMID- 26861819 TI - MOCCASIN: converting MATLAB ODE models to SBML. AB - MATLAB is popular in biological research for creating and simulating models that use ordinary differential equations (ODEs). However, sharing or using these models outside of MATLAB is often problematic. A community standard such as Systems Biology Markup Language (SBML) can serve as a neutral exchange format, but translating models from MATLAB to SBML can be challenging-especially for legacy models not written with translation in mind. We developed MOCCASIN (Model ODE Converter for Creating Automated SBML INteroperability) to help. MOCCASIN can convert ODE-based MATLAB models of biochemical reaction networks into the SBML format. AVAILABILITY AND IMPLEMENTATION: MOCCASIN is available under the terms of the LGPL 2.1 license (http://www.gnu.org/licenses/lgpl-2.1.html). Source code, binaries and test cases can be freely obtained from https://github.com/sbmlteam/moccasin CONTACT: : mhucka@caltech.edu SUPPLEMENTARY INFORMATION: More information is available at https://github.com/sbmlteam/moccasin. PMID- 26861820 TI - Characterization of clinical signs in the human interactome. AB - MOTIVATION: Many diseases are related by shared associated molecules and pathways, exhibiting comorbidities and common phenotypes, an indication of the continuous nature of the human pathological landscape. Although it is continuous, this landscape is always partitioned into discrete diseases when studied at the molecular level. Clinical signs are also important phenotypic descriptors that can reveal the molecular mechanisms that underlie pathological states, but have seldom been the subject of systemic research. Here, we quantify the modular nature of the clinical signs associated with genetic diseases in the human interactome. RESULTS: We found that clinical signs are reflected as modules at the molecular network level, to at least to the same extent as diseases. They can thus serve as a valid complementary partition of the human pathological landscape, with implications for etiology research, diagnosis and treatment. CONTACT: monica.chagoyen@cnb.csic.es SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26861821 TI - TRONCO: an R package for the inference of cancer progression models from heterogeneous genomic data. AB - MOTIVATION: We introduce TRanslational ONCOlogy (TRONCO), an open-source R package that implements the state-of-the-art algorithms for the inference of cancer progression models from (epi)genomic mutational profiles. TRONCO can be used to extract population-level models describing the trends of accumulation of alterations in a cohort of cross-sectional samples, e.g. retrieved from publicly available databases, and individual-level models that reveal the clonal evolutionary history in single cancer patients, when multiple samples, e.g. multiple biopsies or single-cell sequencing data, are available. The resulting models can provide key hints for uncovering the evolutionary trajectories of cancer, especially for precision medicine or personalized therapy. AVAILABILITY AND IMPLEMENTATION: TRONCO is released under the GPL license, is hosted at http://bimib.disco.unimib.it/ (Software section) and archived also at bioconductor.org. CONTACT: tronco@disco.unimib.it SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26861822 TI - Measuring the spatial correlations of protein binding sites. AB - MOTIVATION: Understanding the interactions of different DNA binding proteins is a crucial first step toward deciphering gene regulatory mechanism. With advances of high-throughput sequencing technology such as ChIP-seq, the genome-wide binding sites of many proteins have been profiled under different biological contexts. It is of great interest to quantify the spatial correlations of the binding sites, such as their overlaps, to provide information for the interactions of proteins. Analyses of the overlapping patterns of binding sites have been widely performed, mostly based on ad hoc methods. Due to the heterogeneity and the tremendous size of the genome, such methods often lead to biased even erroneous results. RESULTS: In this work, we discover a Simpson's paradox phenomenon in assessing the genome wide spatial correlation of protein binding sites. Leveraging information from publicly available data, we propose a testing procedure for evaluating the significance of overlapping from a pair of proteins, which accounts for background artifacts and genome heterogeneity. Real data analyses demonstrate that the proposed method provide more biologically meaningful results. AVAILABILITY AND IMPLEMENTATION: An R package is available at http://www.sta.cuhk.edu.hk/YWei/ChIPCor.html CONTACTS: ywei@sta.cuhk.edu.hk or hao.wu@emory.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26861824 TI - Neo-epitopes on methylglyoxal modified human serum albumin lead to aggressive autoimmune response in diabetes. AB - Glyco-oxidation of proteins has implications in the progression of diabetes type 2. Human serum albumin is prone to glyco-oxidative attack by sugars and methylglyoxal being a strong glycating agent may have severe impact on its structure and consequent role in diabetes. This study has probed the methylglyoxal mediated modifications of HSA, the alterations in its immunological characteristics and possible role in autoantibody induction. We observed an exposure of chromophoric groups, loss in the fluorescence intensity, generation of AGEs, formation of cross-linked products, decrease in alpha-helical content, increase in hydrophobic clusters, FTIR band shift, attachment of methylglyoxal to HSA and the formation of N(epsilon)-(carboxyethyl) lysine in the modified HSA, when compared to the native albumin. MG-HSA was found to be highly immunogenic with additional immunogenicity invoking a highly specific immune response than its native counterpart. The binding characteristics of circulating autoantibodies in type 2 diabetes mellitus (DM) patients showed the generation of anti-MG-HSA auto-antibodies in the these patients, that are preferentially recognized by the modified albumin. We propose that MG induced structural perturbations in HSA, result in the generation of neo-epitopes leading to an aggressive auto-immune response and may contribute to the immunopathogenesis of diabetes type 2 associated complications. PMID- 26861823 TI - Predicting physiologically relevant SH3 domain mediated protein-protein interactions in yeast. AB - MOTIVATION: Many intracellular signaling processes are mediated by interactions involving peptide recognition modules such as SH3 domains. These domains bind to small, linear protein sequence motifs which can be identified using high throughput experimental screens such as phage display. Binding motif patterns can then be used to computationally predict protein interactions mediated by these domains. While many protein-protein interaction prediction methods exist, most do not work with peptide recognition module mediated interactions or do not consider many of the known constraints governing physiologically relevant interactions between two proteins. RESULTS: A novel method for predicting physiologically relevant SH3 domain-peptide mediated protein-protein interactions in S. cerevisae using phage display data is presented. Like some previous similar methods, this method uses position weight matrix models of protein linear motif preference for individual SH3 domains to scan the proteome for potential hits and then filters these hits using a range of evidence sources related to sequence-based and cellular constraints on protein interactions. The novelty of this approach is the large number of evidence sources used and the method of combination of sequence based and protein pair based evidence sources. By combining different peptide and protein features using multiple Bayesian models we are able to predict high confidence interactions with an overall accuracy of 0.97. AVAILABILITY AND IMPLEMENTATION: Domain-Motif Mediated Interaction Prediction (DoMo-Pred) command line tool and all relevant datasets are available under GNU LGPL license for download from http://www.baderlab.org/Software/DoMo-Pred The DoMo-Pred command line tool is implemented using Python 2.7 and C ++. CONTACT: gary.bader@utoronto.ca SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. PMID- 26861825 TI - New spiro tria(thia)zolidine-acridines as topoisomerase inhibitors, DNA binders and cytostatic compounds. AB - Three new diphenylsubstituted spirotriazolidine- and thiazolidinone-acridines were prepared and their interaction with calf thymus DNA investigated with UV vis, fluorescence, circular dichroism spectroscopy and viscometry. The binding constants K were estimated to range from 0.34 to 0.93 * 10(4) M(-1). UV-vis, fluorescence and circular dichroism measurements indicated that the compounds act as effective DNA-interacting agents. Electrophoretic separation proved that ligands inhibited topoisomerase I and II. The biological activity of compounds 3, 5 &6 at several different concentrations (10, 20 and 50 MUM) was evaluated both 48 h and 72 h following their addition to HL-60 cancer cells. The results were analysed using various different techniques (MMP detection, changes in metabolic activity/viability and analysis of cell cycle distribution). Acridine was also used as the positive control in these assays. The results from MMP analysis demonstrate the strong effect of 3-diphenylamino-2-(acridin-9-yl)imino-1,3 thiazolidin-4-one (5) on mitochondrial physiology. Cell viability analysis showed that acridine derivatives 3 and 6 were less effective than derivative 5 and the acridine control. PMID- 26861826 TI - Chemical characterization of heteropolysaccharides from green and black teas (Camellia sinensis) and their anti-ulcer effect. AB - In order to obtain polysaccharides from green and black teas (Camellia sinensis), commercial leaves were submitted to infusion and then to alkaline extraction. The extracts were fractionated by freeze-thawing process, giving insoluble and soluble fractions. Complex arabinogalactan protein from the soluble fractions of both teas (GTPS and BTPS) were determined by methylation analysis and (1)H/(13)C HSQC spectroscopy, showing a main chain of (1->3)-beta-Galp, substituted at O-6 by (1->6)-linked beta-Galp with side chains of alpha-Araf and terminal units of alpha-Araf, alpha-Fucp and alpha-Rhap. A highly branched heteroxylan from the insoluble fractions (GTPI and BTPI) showed in methylation analysis and (1)H/(13)C HSQC spectroscopy the main chain of (1->4)-beta-Xylp, substituted in O-3 by alpha Araf, beta-Galp and alpha-Glcp units. Evaluating their gastroprotective activity, the fractions containing the soluble heteropolysaccharides from green (GTPS) and black teas (BTPS) reduced the gastric lesions induced by ethanol. Furthermore, the fraction of insoluble heteropolysaccharides of green (GTPI) and black (BTPI) teas also protected the gastric mucosa. In addition, the maintenance of gastric mucus and reduced glutathione (GSH) levels was involved in the polysaccharides gastroprotection. PMID- 26861827 TI - Discovery of an antibody for pan-ebolavirus therapy. AB - During the latest outbreak of Ebola virus disease in West Africa, monoclonal antibody therapy (e.g., ZMapp) was utilized to treat patients. However, due to the antigenic differences among the five ebolavirus species, the current therapeutic monoclonal antibodies are only effective against viruses of the species Zaire ebolavirus. Although this particular species has indeed caused the majority of human infections in Central and, recently, West Africa, other ebolavirus species (e.g., Sudan ebolavirus and Bundibugyo ebolavirus) have also repeatedly caused outbreaks in Central Africa and thus should not be neglected in the development of countermeasures against ebolaviruses. Here we report the generation of an ebolavirus glycoprotein-specific monoclonal antibody that effectively inhibits cellular entry of representative isolates of all known ebolavirus species in vitro and show its protective efficacy in mouse models of ebolavirus infections. This novel neutralizing monoclonal antibody targets a highly conserved internal fusion loop in the glycoprotein molecule and prevents membrane fusion of the viral envelope with cellular membranes. The discovery of this highly cross-neutralizing antibody provides a promising option for broad acting ebolavirus antibody therapy and will accelerate the design of improved vaccines that can selectively elicit cross-neutralizing antibodies against multiple species of ebolaviruses. PMID- 26861828 TI - Effects of Current-injection Firing with Ag Paste in a Boron Emitter. AB - A high contact resistance for screen-printed contacts was observed when a conventional Ag paste was used on a boron emitter. The results of this study suggest that electron injection during firing is one of the processes that contribute to a lower contact resistance. Larger quantities of Ag precipitates formed upon electron injection into the boron emitter, which was confirmed by observing Ag crystallite or dendrite structures on the boron and by measuring the contact resistance between the boron emitter and the Ag bulk. The electron injected sample had approximately 10000 times lower contact resistance than an untreated sample. The contact resistance of the electron-injected sample was 0.021 mOmega ? cm(2) under optimal conditions, which is lower than that of conventional p-type silicon solar cells. Thus, electron injection can effectively lower contact resistance when using Ag paste in n-type silicon solar cells. During the cooling in the firing process, dissolved Ag ions in the glass layer are formed as dendrites or crystallites/particles. The dendrites are formed earlier than others via electrochemical migration under electron injection conditions. Then, crystallites and particles are formed via a silicon etching reaction. Thus, Ag ions that are not formed as dendrites will form as crystallites or particles. PMID- 26861829 TI - Tumour-induced neoneurogenesis and perineural tumour growth: a mathematical approach. AB - It is well-known that tumours induce the formation of a lymphatic and a blood vasculature around themselves. A similar but far less studied process occurs in relation to the nervous system and is referred to as neoneurogenesis. The relationship between tumour progression and the nervous system is still poorly understood and is likely to involve a multitude of factors. It is therefore relevant to study tumour-nerve interactions through mathematical modelling: this may reveal the most significant factors of the plethora of interacting elements regulating neoneurogenesis. The present work is a first attempt to model the neurobiological aspect of cancer development through a system of differential equations. The model confirms the experimental observations that a tumour is able to promote nerve formation/elongation around itself, and that high levels of nerve growth factor and axon guidance molecules are recorded in the presence of a tumour. Our results also reflect the observation that high stress levels (represented by higher norepinephrine release by sympathetic nerves) contribute to tumour development and spread, indicating a mutually beneficial relationship between tumour cells and neurons. The model predictions suggest novel therapeutic strategies, aimed at blocking the stress effects on tumour growth and dissemination. PMID- 26861830 TI - Patient reported outcomes in three hundred and twenty eight bilateral total knee replacement cases (simultaneous versus staged arthroplasty) using the Oxford Knee Score. AB - PURPOSE: Despite bilateral knee replacement being frequently performed, little data is available to inform on the relative outcomes of each knee for individual patients. The purpose of this study was to compare these outcomes in a series of bilateral total knee replacements (TKRs) performed either simultaneously or at a staged interval. METHODS: We compared outcomes measured by the Oxford Knee Score (OKS; /48) in a series of 656 bilateral TKRs (328 patients). One hundred and fifty-six TKRs were simultaneous and 500 TKRs staged. RESULTS: Of the staged patients, in 164 (65.6 %) the post-operative OKS in their second TKR matched the first, it was worse in 57 (22.8 %) and better in 29 (11.6 %). The trend was towards a worse OKS in the second staged TKR (p = 0.003). Mean improvement was similar in simultaneous cases to the first staged TKR (24.3 vs. 24.0; p = 0.883) but significantly less in second staged TKRs (20.2; p < 0.001) due to higher pre operative scores. CONCLUSIONS: Individual patients attained a comparable post operative score in both their knees, independent of age, pre-operative function and the duration of any staging interval. PMID- 26861831 TI - Portable open-circuit spirometry systems. AB - BACKGROUND: The purpose of this review is to describe the evolution of portable open-circuit spirometry systems, and discuss their validity, reliability, and principles of operation. METHODS: Eleven devices were selected for review: the Oxylog, Aerosport KB1-C, Cosmed K2, Cosmed K4RQ, Cosmed K4b2, MetaMax I, MetaMax II, Metamax3B/VmaxST, Medgraphics VO2000, Oxycon Mobile I and Oxycon Mobile II. The validity (compared to the Douglas bag method [DBM]) and reliability of each device for measuring VO2 was summarized. RESULTS: Mean differences in resting measurements of VO2 were within +/-0.05 L/min for all devices except one (difference of 0.17 L/min). When compared to the DBM, VO2 differences for all devices ranged from 0.01 L/min to 0.29 L/min during submaximal intensity exercise and from 0.01 L/min to 0.36 L/min during vigorous/maximal intensity. During submaximal and maximal intensities, ICC ranged from 0.66-0.99 and CV ranged from 2.0-14.2%. Of these devices, four used breath-by-breath technology and six used micro-proportional sampling technology. Validity and reliability of devices did not seem to differ between methods of gas collection. CONCLUSIONS: Of the three commercially available devices in 2015, all were found to be reliable. Two of the three systems (Cosmed K4b2 and Oxycon Mobile II) provided valid estimates of VO2 (mean values within +/-0.10 L/min of DBM) during rest, and submaximal and maximal intensities, while the MetaMax3B slightly overestimated VO2, particularly at maximal exercise. PMID- 26861832 TI - Exhaustive exercise decreases L-type calcium current. AB - BACKGROUND: This study investigated effects of exhaustive exercise on L-type calcium current (ICa,L) and the putative intracellular cascade responsible for the effects. METHODS: Rats were randomly divided into three treatment groups: sedentary (without exercise), exercised to exhaustion and salubrinal injection before each exhaustive exercise period. Exercise group rats were forced to swim until exhaustion each time for 9 days with 5% body weight attached to the head. Salubrinal (1 mg/kg) or an equivalent volume of placebo solution (dimethyl sulfoxide) was injected via the intraperitoneal route daily for the first 3 days, followed by subcutaneous injections of salubrinal (0.5 mg/kg) or placebo solution daily for 9 days (starting 30 min before exercise). After a 1-day recovery period, whole-cell patch clamping was used to investigate the L-type Ca2+ current (ICa,L), with sedentary control rats. Additionally, endoplasmic reticulum (ER) chaperone protein levels were analyzed. RESULTS: Exhaustive exercise triggered ER stress, demonstrated by elevated expression of ER stress markers: phospho eIF2alpha, CCAT/enhancer-binding homologous protein (CHOP) and caspase-12. Compared to controls, ICa,L was inhibited by exhaustive exercise, which was blocked by salubrinal, a selective eIF2alpha dephosphorylation inhibitor used to inhibit ER stress. These results suggest that ER stress participates in regulation of ICa,L. However, exhaustive exercise did not change the voltage dependence of steady-state activation and inactivation of ICaL, and salubrinal infusion caused no difference in voltage dependence of steady-state activation and inactivation of ICa,L. CONCLUSION: Exhaustive exercise activates ER stress, thus inhibiting ICaL, which may change the action potential duration and contribute to proarrhythmia. PMID- 26861837 TI - Compassion fatigue: A personal perspective. PMID- 26861833 TI - Thickness scaling of atomic-layer-deposited HfO2 films and their application to wafer-scale graphene tunnelling transistors. AB - The downscaling of the capacitance equivalent oxide thickness (CET) of a gate dielectric film with a high dielectric constant, such as atomic layer deposited (ALD) HfO2, is a fundamental challenge in achieving high-performance graphene based transistors with a low gate leakage current. Here, we assess the application of various surface modification methods on monolayer graphene sheets grown by chemical vapour deposition to obtain a uniform and pinhole-free ALD HfO2 film with a substantially small CET at a wafer scale. The effects of various surface modifications, such as N-methyl-2-pyrrolidone treatment and introduction of sputtered ZnO and e-beam-evaporated Hf seed layers on monolayer graphene, and the subsequent HfO2 film formation under identical ALD process parameters were systematically evaluated. The nucleation layer provided by the Hf seed layer (which transforms to the HfO2 layer during ALD) resulted in the uniform and conformal deposition of the HfO2 film without damaging the graphene, which is suitable for downscaling the CET. After verifying the feasibility of scaling down the HfO2 thickness to achieve a CET of ~1.5 nm from an array of top-gated metal oxide-graphene field-effect transistors, we fabricated graphene heterojunction tunnelling transistors with a record-low subthreshold swing value of <60 mV/dec on an 8" glass wafer. PMID- 26861834 TI - Lay Health Workers experience of a tailored knowledge translation intervention to improve job skills and knowledge: a qualitative study in Zomba district Malawi. AB - BACKGROUND: Like many sub-Saharan African countries, Malawi is facing a critical shortage of skilled healthcare workers. In response to this crisis, a formal cadre of lay health workers (LHW) has been established and now carries out several basic health care services, including outpatient TB care and adherence support. While ongoing training and supervision are recognized as essential to the effectiveness of LHW programs, information is lacking as to how these needs are best addressed. The objective of this qualitative study was to explore LHWs responses to a tailored knowledge translation intervention they received, designed to address a previously identified training and knowledge gap. METHODS: Forty-five interviews were conducted with 36 healthcare workers. Fourteen to sixteen interviews were done at each of 3 evenly spaced time blocks over a one year period, with 6 individuals interviewed more than once to assess for change both within and across individuals overtime. RESULTS: Reported benefits of the intervention included: increased TB, HIV, and job-specific knowledge; improved clinical skills; and increased confidence and satisfaction with their work. Suggestions for improvement were less consistent across participants, but included: increasing the duration of the training, changing to an off-site venue, providing stipends or refreshments as incentives, and adding HIV and drug dosing content. CONCLUSIONS: Despite the significant departure of the study intervention from the traditional approach to training employed in Malawi, the intervention was well received and highly valued by LHW participants. Given the relative low cost and flexibility of the methods employed, this appears a promising approach to addressing the training needs of LHW programs, particularly in Low- and Middle income countries where resources are most constrained. PMID- 26861842 TI - Giant conductivity switching of LaAlO3/SrTiO3 heterointerfaces governed by surface protonation. AB - Complex-oxide interfaces host a diversity of phenomena not present in traditional semiconductor heterostructures. Despite intense interest, many basic questions remain about the mechanisms that give rise to interfacial conductivity and the role of surface chemistry in dictating these properties. Here we demonstrate a fully reversible >4 order of magnitude conductance change at LaAlO3/SrTiO3 (LAO/STO) interfaces, regulated by LAO surface protonation. Nominally conductive interfaces are rendered insulating by solvent immersion, which deprotonates the hydroxylated LAO surface; interface conductivity is restored by exposure to light, which induces reprotonation via photocatalytic oxidation of adsorbed water. The proposed mechanisms are supported by a coordinated series of electrical measurements, optical/solvent exposures, and X-ray photoelectron spectroscopy. This intimate connection between LAO surface chemistry and LAO/STO interface physics bears far-reaching implications for reconfigurable oxide nanoelectronics and raises the possibility of novel applications in which electronic properties of these materials can be locally tuned using synthetic chemistry. PMID- 26861844 TI - In-electrode vs. on-electrode: ultrasensitive Faraday cage-type electrochemiluminescence immunoassay. AB - A new-concept of an "in-electrode" Faraday cage-type electrochemiluminescence immunoassay (ECLIA) method for the ultrasensitive detection of neurotensin (NT) was reported with capture antibody (Ab1)-nanoFe3O4@graphene (GO) and detector antibody (Ab2)&N-(4-aminobutyl)-N-ethylisoluminol (ABEI)@GO, which led to about 1000-fold improvement in sensitivity by extending the Helmholtz plane (OHP) of the proposed electrode assembly effectively. PMID- 26861843 TI - Genome-wide identification and characterization of long intergenic noncoding RNAs and their potential association with larval development in the Pacific oyster. AB - An increasing amount of evidence suggests that long intergenic noncoding RNAs (lincRNAs) may play diverse roles in many cellular processes. However, little is known about lincRNAs in marine invertebrates. Here, we presented the first identification and characterization of lincRNAs in the Pacific oyster (Crassostrea gigas). We developed a pipeline and identified 11,668 lincRNAs in C. gigas based on RNA-Seq resources available. These lincRNAs exhibited many common characteristics with vertebrate lincRNAs: relatively short length, low exon numbers, low expression, and low sequence conservation. 1,175 lincRNAs were expressed in a tissue-specific manner, with 35.2% preferentially expressed in male gonad. 776 lincRNAs were specifically expressed in juvenile during different developmental stages. In addition, 47 lincRNAs were found to be potentially related to oyster settlement and metamorphosis. Such diverse temporal and spatial patterns of expression suggest that these lincRNAs might function in cell differentiation during early development, as well as sex differentiation and reproduction. Based on a co-expression network analysis, five lincRNAs were detected that have an expression correlation with key hub genes in four modules significantly correlated with larval development. Our study provides the first large-scale identification of lincRNAs in molluscs and offers new insights into potential functions of lincRNAs in marine invertebrates. PMID- 26861845 TI - The Peridural Membrane of the Human Spine is Well Innervated. AB - There is evidence that low back pain may originate from a peridural membrane (PDM) at the inferior and medial aspect of neural foramen of the lumbar spine. The objective of this investigation was to determine if this membrane contains neural elements suggestive of sensory innervation with nociceptive function. Spines of four embalmed and three non-embalmed human cadavers were dissected using a sagittal approach to the neural foramen. Seventeen samples of the peridural membrane overlying the neural foramen were collected for immunohistochemistry (IHC) examination by light microscopy and transmission electron microscopy (TEM). Chromagin tagged antibodies to protein gene product 9.5 (PGP9.5) and S-100, and fluorescent antibodies to substance P and calcitonin gene related peptide (CGRP) were used to label neural structures in tissue sections cut from paraffin embedded blocks. This approach allows good visualization of all neural elements, small sensory, and nociceptive nerve fibers in particular. Neural elements were found in all samples. Marked presence of small nerve fibers was observed in 12 of 15 samples. IHC and TEM evaluation revealed myelinated as well as unmyelinated fibers in the peridural membrane. CGRP and substance P immunoreactive fibers indicative of nociceptive function were abundant. These findings confirm and expand evidence that the peridural membrane in human is well innervated and contains sensory nociceptive nerve fibers suggestive of a nociceptive function of the membrane. PMID- 26861846 TI - Current and Future Considerations for the Treatment of Hospital-Acquired Pneumonia. AB - Hospital-acquired pneumonia (HAP) and health-care-associated pneumonia (HCAP) are leading causes of death, morbidity, and resource utilization in hospitalized patients, and are associated with a broad range of Gram-positive and Gram negative pathogens. Here, we discuss the different definitions of HAP and HCAP, review current guidelines regarding the treatment of these conditions, highlight the shortcomings of current therapeutic options, and discuss new antibiotic treatments. To optimize therapeutic outcomes in patients with HAP/HCAP, initial antimicrobial treatment must be appropriate and should be given as soon as possible; inappropriate or delayed therapy greatly increases morbidity and mortality. Selection of the most appropriate antimicrobial agent depends on the causative pathogen(s); initial broad-spectrum therapy is commonly recommended and should cover all pathogens that may be present. Treatment selection should also take into consideration the following factors: knowledge of underlying local risk factors for antimicrobial resistance, disease staging, and risk factors related to specific pathogens such as Pseudomonas aeruginosa, Acinetobacter spp., and methicillin-resistant Staphylococcus aureus (MRSA). Guidelines consistently emphasize the importance of treating HAP and HCAP with early and appropriate broad-spectrum antibiotics, and recent developments in this field have resulted in the availability of several additional treatment options. Telavancin shows potent activity against Gram-positive bacteria including MRSA and can be administered once daily; it was approved in the USA and European Union for the treatment of HAP after demonstrating non-inferiority to vancomycin. Ceftobiprole medocaril exhibits rapid antimicrobial activity against a broad range of both Gram-positive and Gram-negative pathogens, including MRSA. It was approved for the treatment of HAP (excluding ventilator-associated pneumonia) and community acquired pneumonia in Europe in 2013. These new treatments may offer effective alternative therapeutic options for the management of HAP. FUNDING: Basilea Pharmaceutica Ltd., Basel, Switzerland. PMID- 26861847 TI - Sustainability of Intraocular Pressure Reduction of Travoprost Ophthalmic Solution in Subjects with Normal Tension Glaucoma. AB - INTRODUCTION: We examined the sustainability of the intraocular pressure (IOP) lowering efficacy of travoprost (0.004%) ophthalmic solution in subjects with normal tension glaucoma (NTG). METHODS: Travoprost ophthalmic solution was given once daily at 9 PM to subjects with newly diagnosed NTG or with NTG who had not received any ocular hypotensives within the previous 30 days. IOP was measured at three time points (9 AM, 1 PM, and 5 PM) at baseline and week 12 visits, and at one time point (9 AM) at week 4 and week 8 visits. Conjunctival hyperemia, superficial punctate keratopathy, and other adverse events were evaluated during the observation period. RESULTS: Thirty subjects (12 males and 18 females; mean age 65.6 years) from 32 subjects enrolled were included in the efficacy analysis. The mean IOPs (+/-standard deviation) of 16.6 +/- 1.4, 15.7 +/- 1.8, and 15.7 +/- 2.2 mmHg at 9 AM, 1 PM, and 5 PM, respectively, at baseline reduced significantly to the mean IOPs of 13.0 +/- 1.8, 12.7 +/- 1.8, and 12.8 +/- 1.6 mmHg, respectively, at week 12 (P < 0.0001 for every time point). Together with the mean IOPs of 13.4 +/- 1.9 mmHg at week 4 and 13.2 +/- 1.9 mmHg at week 8, the pooled IOP during the observation period for up to 12 weeks showed a statistically and clinically significant reduction of IOP at 9 AM. (3.4 mmHg or 20.3% reduction from baseline, P < 0.0001). There were no adverse events leading to treatment discontinuation. CONCLUSION: This multi-center collaborative study suggests that IOP-lowering efficacy of travoprost ophthalmic solution persists during the day at the clinically relevant level in subjects with NTG. FUNDING: Alcon Japan Ltd. TRIAL REGISTRATION: University Hospital Medical Information Network, UMIN ID: 000011621. PMID- 26861848 TI - Nicorandil, Gastrointestinal Adverse Drug Reactions and Ulcerations: A Systematic Review. AB - INTRODUCTION: Nicorandil is a popular anti-anginal drug in Europe and Japan. Apart from some common adverse drug reactions (ADR), its safety is satisfactory. Several reports have suggested a link between nicorandil, gastrointestinal (GI) ulceration and fistulas. The review aims to critically appraise, synthesize and present the available evidence of all known GI ADR per anatomical location. METHODS: The study complied with the PRISMA statement. Literature and pharmacovigilance databases were used to provide rate and/or calculate parameters (median age, median dose, history of symptoms, length of therapy and healing time after withdrawal of the drug). Differences in distribution of quantitative variables were analyzed via Mann-Whitney test. Correlation between quantitative variables was assessed with a Spearman's correlation coefficient. A p value <0.05 was significant. RESULTS: Oral ulcerations occur in 0.2% of the subjects, anal ulcerations are present between 0.07% and 0.37% of patients. Oral and distal GI involvements are the most common ADR (28-29% and 27-31% of all GI ADR, respectively). The hepatobiliary system, the pancreas and salivary glands are not affected by nicorandil exposure. The time to develop oral ulcerations is 74 weeks among people on <30 mg/day compared to only 7.5 weeks in individuals on higher regimens (p = 0.47). There is a significant correlation between dose and ulcer healing time (Spearman's 0.525, p < 0.001). CONCLUSIONS: Ulcerative disease is a very commonly reported GI ADR. A delayed ulcerative tendency supports the hypothesis of an ulcerogenic metabolite. Nicorandil seems to act as a cause of the ulcerations, but appears to also work in synergy with other promoting factors. Whether the action of the metabolites relies on a specific mechanism or a simple chemical ulceration is still to be established. PMID- 26861850 TI - Reducing the graphene grain density in three steps. AB - The production of large-scale, single crystalline graphene is a requirement for enhancing its electronic, mechanical, and chemical properties. Chemical vapor deposition (CVD) has shown the potential to grow high quality graphene but the simultaneous nucleation of many grains limits their achievable domain size. We report here that ultralow nucleation densities can be achieved through multi-step optimization of the catalyst morphology. First, annealing in a hydrogen-free environment is required to retain a surface copper oxide which decreases the nucleation density. Second, CuO was found to be the relevant copper species for this process and air oxidation of the copper foil at 200 degrees C maximizes its concentration. Both pre-treatment steps were found to affect the morphology of the catalyst and a direct correlation between nucleation density and surface roughness was found which indicates that the primary role of the oxidation step is the decrease in catalyst roughness. To further enhance this determining parameter, confined CVD was carried out after sample oxidation and hydrogen-free annealing. Each of these three steps reduces the grain density by approximately one order of magnitude resulting in ultralow nucleation densities of 1.23 grains/mm(2) and high quality, single-crystalline graphene grains of several millimeter sizes were grown using this method. PMID- 26861851 TI - Hydration lubrication and shear-induced self-healing of lipid bilayer boundary lubricants in phosphatidylcholine dispersions. AB - Measurements of normal and shear (frictional) forces between mica surfaces across small unilamellar vesicle (SUV) dispersions of the phosphatidylcholine (PC) lipids DMPC (14:0), DPPC (16:0) and DSPC (18:0) and POPC (16:0, 18:1), at physiologically high pressures, are reported. We have previously studied the normal and shear forces between two opposing surfaces bearing PC vesicles across pure water and showed that liposome lubrication ability improved with increasing acyl chain length, and correlated strongly with the SUV structural integrity on the substrate surface (DSPC > DPPC > DMPC). In the current study, surprisingly, we discovered that this trend is reversed when the measurements are conducted in SUV dispersions, instead of pure water. In their corresponding SUV dispersion, DMPC SUVs ruptured and formed bilayers, which were able to provide reversible and reproducible lubrication with extremely low friction (MU < 10(-4)) up to pressures of 70-90 atm. Similarly, POPC SUVs also formed bilayers which exhibited low friction (MU < 10(-4)) up to pressures as high as 160 atm. DPPC and DSPC SUVs also provided good lubrication, but with slightly higher friction coefficients (MU = 10(-3)-10(-4)). We believe these differences originate from fast self healing of the softer surface layers (which are in their liquid disordered phase, POPC, or close to it, DMPC), which renders the robustness of the DPPC or DSPC (both in their solid ordered phase) less important in these conditions. Under these circumstances, the enhanced hydration of the less densely packed POPC and DMPC surface layers is now believed to play an important role, and allows enhanced lubrication via the hydration lubrication mechanism. Our findings may have implications for the understanding of complex biological systems such us biolubrication of synovial joints. PMID- 26861849 TI - Lack of effect of adenosine on the function of rodent osteoblasts and osteoclasts in vitro. AB - Extracellular ATP, signalling through P2 receptors, exerts well-documented effects on bone cells, inhibiting mineral deposition by osteoblasts and stimulating the formation and resorptive activity of osteoclasts. The aims of this study were to determine the potential osteotropic effects of adenosine, the hydrolysis product of ATP, on primary bone cells in vitro. We determined the effect of exogenous adenosine on (1) the growth, alkaline phosphatase (TNAP) activity and bone-forming ability of osteoblasts derived from the calvariae of neonatal rats and mice and the marrow of juvenile rats and (2) the formation and resorptive activity of osteoclasts from juvenile mouse marrow. Reverse transcription polymerase chain reaction (RT-PCR) analysis showed marked differences in the expression of P1 receptors in osteoblasts from different sources. Whilst mRNA for the A1 and A2B receptors was expressed by all primary osteoblasts, A2A receptor expression was limited to rat bone marrow and mouse calvarial osteoblasts and the A3 receptor to rat bone marrow osteoblasts. We found that adenosine had no detectable effects on cell growth, TNAP activity or bone formation by rodent osteoblasts in vitro. The analogue 2-chloroadenosine, which is hydrolysed more slowly than adenosine, had no effects on rat or mouse calvarial osteoblasts but increased TNAP activity and bone formation by rat bone marrow osteoblasts by 30-50 % at a concentration of 1 MUM. Osteoclasts were found to express the A2A, A2B and A3 receptors; however, neither adenosine (<=100 MUM) nor 2-chloroadenosine (<=10 MUM) had any effect on the formation or resorptive activity of mouse osteoclasts in vitro. These results suggest that adenosine, unlike ATP, is not a major signalling molecule in the bone. PMID- 26861852 TI - Expression, purification and characterization of a thermostable leucine dehydrogenase from the halophilic thermophile Laceyella sacchari. AB - OBJECTIVE: A potential thermotolerant L-leucine dehydrogenase from Laceyella sacchari (Ls-LeuDH) was over-expressed in E. coli, purified and characterized. RESULTS: Ls-LeuDH had excellent thermostability with a specific activity of 183 U/mg at pH 10.5 and 25 degrees C. It retained a high activity in 200 mM carbonate buffer from pH 9.5 to 11. The optimal temperature for Ls-LeuDH was 60 degrees C. CONCLUSION: It is the first time that a thermostable and highly active LeuDH originating from L. sacchari has been characterized. It may be useful for medical and pharmaceutical applications. PMID- 26861853 TI - Simultaneous Cr(VI) reduction and Zn(II) biosorption by Stenotrophomonas sp. and constitutive expression of related genes. AB - OBJECTIVES: To investigate simultaneous Cr(VI) reduction and Zn(II) biosorption by a microorganism. RESULTS: A new isolate, Stenotrophomonas sp. TD3, simultaneously reduced Cr(VI) and achieved Zn(II) biosorption. The strain was resistant to other metals and salts, and its Zn biosorption could be stimulated greatly by CaCl2 and MgCl2, which has not been reported previously. Three putative Cr- or Zn-related genes, chrR, zupT and hmrE, were amplified and measured using quantitative real-time PCR to evaluate their mRNA expression levels in Stenotrophomonas sp. The three putative genes were not sensitive to Cr(6+), Zn(2+), Ca(2+), and Mg(2+), which suggested that they were constitutively expressed in Stenotrophomonas sp. TD3. CONCLUSIONS: These results improve our understanding of the mechanism and suggest that the strain is a potential candidate for facilitating remediation of Cr(VI) and Zn contaminated sites. PMID- 26861854 TI - The Trypanosomatid Pr77-hallmark contains a downstream core promoter element essential for transcription activity of the Trypanosoma cruzi L1Tc retrotransposon. AB - BACKGROUND: Trypanosomatid genomes are highly colonized by non-LTR retroelements that make up to 5% of the nuclear genome. These elements are mainly accumulated in the strand switch regions (SSRs) where polycistronic transcription is initiated and have a 77 nt-long sequence--Pr77--at their 5' ends. L1Tc is the best represented retrotransposon in the Trypanosoma cruzi genome and is a potentially functional autonomous element that encodes its own retrotransposition machinery. The Pr77 of the T. cruzi L1Tc element activates gene transcription via RNA polymerase II, generating abundant, unspliced transcripts which are translated. RESULTS: The present manuscript describes the identification of a downstream core promoter element (DPE) in the L1Tc Pr77 sequence. Just four nucleotides long (CGTG), it covers in Pr77 positions +25 to +28 of the described L1Tc transcription start site. The Pr77-DPE motif is conserved in terms of sequence composition and position in the Pr77 of most trypanosomatid non-LTR retrotransposons, independent of the coding or non-coding capacity of these retroelements. Transcription assays in T. cruzi stable transfectants with vector containing point mutations at 17 locations of the Pr77 nucleotide sequence evidence that the DPE motif is essential for the promoter function of Pr77. Furthermore, the obtained data show that other nucleotides also contributed to the promoter function of Pr77. In addition, the presented results indicate that parasite nuclear proteins specifically bind to different regions of the Pr77 sequence although the strongest binding is to the DPE motif. Moreover, it is shown that the DPE sense single-stranded sequence is being required in DNA protein recognition of nuclear factors. CONCLUSIONS: The Pr77 sequence present in most of non-LTR retrotransposons of trypanosomatids contains a downstream core promoter element (DPE) which is conserved in terms of nucleotide composition and location. The Pr77-DPE motif is essential for the transcriptional activity of Pr77 although other nucleotides are also involved. DPE has a high affinity binding for nuclear proteins in T. cruzi. The wide retroelement-mediated distribution of Pr77 suggests that it may represent an important tool for regulating gene expression in trypanosomatids. PMID- 26861855 TI - Bioactivity of sol-gel-derived TiO2 coating on polyetheretherketone: In vitro and in vivo studies. AB - A polyetheretherketone (PEEK) surface was modified using a sol-gel-derived TiO2 coating in order to confer bone-bonding ability. To enhance the bonding strength of the coating layer, pretreatment with either O2 plasma or sandblasting was performed prior to sol-gel coating. Additionally, post-treatment with acid was carried out to confer apatite (calcium phosphate)-forming ability to the surface. Biomechanical and histological analyses performed using an in vivo rabbit tibia model showed that PEEK surfaces modified with sol-gel-derived TiO2 and acid post treatment had better bone-bonding properties than uncoated PEEK surfaces. These modified surfaces also performed well in terms of their in vitro cell responses due to their modified surface chemistries and topographies. Although O2 plasma or sandblasting treatment were, for the most part, equivocal in terms of performance, we conclude that sol-gel-derived TiO2 coating followed by acid post treatment significantly improves the bone bonding ability of PEEK surfaces, thus rendering them optimal for their use in surgical implants. STATEMENT OF SIGNIFICANCE: The role of polyetheretherketone (PEEK) as an alternative biomaterial to conventional metallic implant materials has become increasingly important. However, its low bone bonding ability is yet to be resolved. This in vivo and in vitro investigation on the functionalization of PEEK surfaces highlights the utility of this material in clinical interventions that require implants, and may extend range of applications of PEEK. PMID- 26861856 TI - Increased arterial stiffness predicts cognitive impairment in hemodialysis patients. AB - Introduction Cognitive impairment is a major, but underdiagnosed, risk factor for negative outcomes in patients with chronic kidney disease (CKD). The main goal of this study was to evaluate, for the first time, the relationship between arterial stiffness and cognitive impairment in a cohort of hemodialysis patients. Methods We prospectively analyzed the cognitive function and pulse wave velocity (PWV) of 72 hemodialysis patients, mean age 56.54 +/- 13.96 y, from two Romanian dialysis centers. We administered to all patients the Mini Mental State Examination (MMSE), Trail Making Test Part-A (TMTA) and Part-B (TMTB), and Mini-Cog Test. Radial arterial waveforms during 40 cardiac cycles were recorded in each patient. Findings Mean MMSE score was 25.13 +/- 3.47, mean MiniCog score was 3.51 +/- 1.18, mean TMTA (sec) was 103.77 +/- 53.13 and mean TMTB (sec) was 214.93 +/- 112.25. In linear unadjusted regression, PWV values were associated with worse MMSE scores (beta = -0.36, P = 0.001, 95% CI: -0.68 to -0.17), and MiniCog scores (beta = -0.26, P = 0.02, 95% CI: -0.19 to -0.01). Also, PWV value was significant associated with TMTA test, but not with TMTB. After further adjustments, PWV remained a strong predictor for cognitive impairment measured by MMSE, TMTA, MiniCog, but not for TMTB. Discussion Cognitive impairment was associated with higher PWV values in our cohort. Further evidence is needed in order to support arterial stiffness as a long-term predictor for cognitive decline in ESRD patients. PMID- 26861857 TI - The Antiplatelet Effect of Clopidogrel Decreases With Patient Age. AB - Recent data suggest that clopidogrel-mediated platelet inhibition is age dependent. However, so far the effect of age on adenosine diphosphate (ADP) inducible platelet reactivity has only been investigated by test systems measuring surrogate markers of platelet aggregation. We therefore sought to study the impact of age on platelet inhibition by clopidogrel by whole-blood flow cytometry. Platelet surface P-selectin expression, activated glycoprotein (GP) IIb/IIIa, and monocyte-platelet aggregate (MPA) formation were determined by flow cytometry in 302 patients with dual antiplatelet therapy after successful angioplasty and stenting. Patient age was independently associated with ADP inducible P-selectin expression, GPIIb/IIIa, and MPA formation (all P < .05). Moreover, platelet surface expressions of P-selectin and activated GPIIb/IIIa were significantly higher in patients >=75 years compared with younger patients (both P <= .004). Likewise, MPA formation was significantly more pronounced in patients >=75 years ( P = .02). Finally, high P-selectin and high GPIIb/IIIa were significantly more frequent in patients >=75 years compared with younger patients (both P < .001). Further, high MPA ADP occurred more frequently in patients >=75 years compared to younger patients ( P < .05). In conclusion, the antiplatelet effect of clopidogrel decreases with patient age. PMID- 26861858 TI - Intravenous Enoxaparin Versus Unfractionated Heparin in Elderly Patients Undergoing Primary Percutaneous Coronary Intervention: An Analysis of the Randomized ATOLL Trial. AB - Elderly (>=75 years old) patients with ST-segment elevation myocardial infarction (STEMI) have higher ischemic and bleeding risk compared with those <75 years old. We investigated the efficacy and safety of intravenous (IV) enoxaparin versus IV unfractionated heparin (UFH) in elderly patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. A prespecified analysis of the Acute Myocardial Infarction Treated with Primary Angioplasty and Intravenous Enoxaparin or Unfractionated Heparin to Lower Ischemic and Bleeding Events at Short- and Long-term Follow-up (ATOLL) study was performed examining the 30-day outcomes in the elderly patients. Of the 165 elderly patients in the ATOLL study, 85 patients received IV enoxaparin 0.5 mg/kg and 80 patients received IV UFH. Intravenous enoxaparin did not reduce the primary end point, the main secondary efficacy end point, major bleeding, major or minor bleeding, and all-cause mortality compared with IV UFH. The rate of minor bleeding (5.9% vs 22.8%, P adjusted = .01) was significantly lower with IV enoxaparin compared with IV UFH. Intravenous enoxaparin appears to be a safe alternative to IV UFH in primary PCI of the elderly patients with STEMI. PMID- 26861859 TI - Comparative study of efficacy, rapidity of detection, and cost-effectiveness of potassium hydroxide, calcofluor white, and Chicago sky blue stains in the diagnosis of dermatophytoses. AB - BACKGROUND: The diagnosis of superficial mycosis such as dermatophytosis is often done clinically. However, in difficult cases, a rapid test with high sensitivity and specificity helps in the immediate confirmation and administration of treatment. METHODS: The efficacy, rapidity of detection, and cost-effectiveness of KOH preparation, calcofluor white (CW) stain, and Chicago sky blue (CSB) stain in the identification of fungal elements were assessed in patients with dermatophytoses attending the dermatology clinic of a tertiary care hospital. All three tests were performed on each sample collected from 73 patients according to standard procedure. The slides were examined after 5 and 30 minutes in * 10 and * 40 magnifications. The sensitivity and specificity of CW and CSB at 5 and 30 minutes were calculated using KOH preparation as the standard test. RESULTS: CSB stain showed highest positivity (94.5%) within 5 minutes when compared to KOH (75.3%) and CW (83.5%). After 30 minutes, positivity increased in KOH (84.9%) and CW stains (89%), but it remained the same in CSB stain. Both CW and CSB stains when compared to 10% KOH are equally sensitive (100%), but CW was more specific (72.7%), particularly at 30 minutes. When cost of performing tests on 100 specimens is considered, KOH, CW, and CSB stains cost Rs 5, 100, and 15, respectively. CONCLUSION: CSB stain is a better stain for rapid diagnosis of dermatophytoses because of ease of performance, rapidity of detection, better appreciation of morphology of fungal elements, and cost effectiveness. PMID- 26861860 TI - Biochemistry and physiology within the framework of the extended synthesis of evolutionary biology. AB - Functional biologists, like Claude Bernard, ask "How?", meaning that they investigate the mechanisms underlying the emergence of biological functions (proximal causes), while evolutionary biologists, like Charles Darwin, asks "Why?", meaning that they search the causes of adaptation, survival and evolution (remote causes). Are these divergent views on what is life? The epistemological role of functional biology (molecular biology, but also biochemistry, physiology, cell biology and so forth) appears essential, for its capacity to identify several mechanisms of natural selection of new characters, individuals and populations. Nevertheless, several issues remain unsolved, such as orphan metabolic activities, i.e., adaptive functions still missing the identification of the underlying genes and proteins, and orphan genes, i.e., genes that bear no signature of evolutionary history, yet provide an organism with improved adaptation to environmental changes. In the framework of the Extended Synthesis, we suggest that the adaptive roles of any known function/structure are reappraised in terms of their capacity to warrant constancy of the internal environment (homeostasis), a concept that encompasses both proximal and remote causes. PMID- 26861861 TI - Nonmotor features of Parkinson's disease subtypes. AB - Parkinson's disease is highly heterogeneous in early clinical features and later outcomes. This makes classifying subgroups of PD relevant to clinical research and practice, particularly if they are prognostically relevant. Subgroups have been defined both on the basis of motor and nonmotor features, and subgroups have been determined either empirically, based on clinical observation, or using data driven analytic techniques. Previous studies have examined both the overall number and the nature of nonmotor symptoms and signs in tremor-dominant compared with non-tremor-dominant subtypes, and longitudinal studies identify nonmotor symptoms as important markers of prognosis and important defining features of PD subtypes. Autonomic features seem to preferentially affect individuals with non tremor-dominant PD subtype early in the disease. Later in the disease cognitive disturbance distinguishes this phenotype. Pathological and neuroimaging studies provide substantial evidence for fundamental biological differences between tremor-dominant and postural instability gait disorder/akinetic-rigid subtypes. Biomarker studies point toward non-tremor-dominant PD as representing more advanced and diffuse neurodegeneration than tremor-dominant PD, encompassing dopaminergic and nondopaminergic as well as synuclein and nonsynuclein (Abeta) pathologies. This aligns with clinical studies that find a higher burden of nonmotor symptoms in non-tremor-dominant PD. The mounting evidence for the relevance of nonmotor features in PD subtypes behooves us to begin to investigate the biological underpinnings of subtypes defined by both motor and nonmotor features. This may be challenging, as PD subtypes are unlikely to be distinct nonoverlapping entities but are more likely to represent typical phenotypes within a multidimensional spectrum resulting from variable contributions of a number of simultaneous pathological processes. (c) 2016 International Parkinson and Movement Disorder Society. PMID- 26861862 TI - Estimating malaria transmission intensity from Plasmodium falciparum serological data using antibody density models. AB - BACKGROUND: Serological data are increasingly being used to monitor malaria transmission intensity and have been demonstrated to be particularly useful in areas of low transmission where traditional measures such as EIR and parasite prevalence are limited. The seroconversion rate (SCR) is usually estimated using catalytic models in which the measured antibody levels are used to categorize individuals as seropositive or seronegative. One limitation of this approach is the requirement to impose a fixed cut-off to distinguish seropositive and negative individuals. Furthermore, the continuous variation in antibody levels is ignored thereby potentially reducing the precision of the estimate. METHODS: An age-specific density model which mimics antibody acquisition and loss was developed to make full use of the information provided by serological measures of antibody levels. This was fitted to blood-stage antibody density data from 12 villages at varying transmission intensity in Northern Tanzania to estimate the exposure rate as an alternative measure of transmission intensity. RESULTS: The results show a high correlation between the exposure rate estimates obtained and the estimated SCR obtained from a catalytic model (r = 0.95) and with two derived measures of EIR (r = 0.74 and r = 0.81). Estimates of exposure rate obtained with the density model were also more precise than those derived from catalytic models. CONCLUSION: This approach, if validated across different epidemiological settings, could be a useful alternative framework for quantifying transmission intensity, which makes more complete use of serological data. PMID- 26861863 TI - Mitochondrial and oxidative stress genes are differentially expressed in neutrophils of sJIA patients treated with tocilizumab: a pilot microarray study. AB - BACKGROUND: Various pathways involved in the pathogenesis of sJIA have been identified through gene expression profiling in peripheral blood mononuclear cells (PBMC), but not in neutrophils. Since neutrophils are important in tissue damage during inflammation, and are elevated as part of the acute phase response, we hypothesised that neutrophil pathways could also be important in the pathogenesis of sJIA. We therefore studied the gene profile in both PBMC and neutrophils of sJIA patients treated with tocilizumab. METHODS: We studied the transcriptomes of peripheral blood mononuclear cells (PBMC) and neutrophils from eight paired samples obtained from 4 sJIA patients taken before and after treatment, selected on the basis that they achieved ACR90 responses within 12 weeks of therapy initiation with tocilizumab. RNA was extracted and gene expression profiling was performed using Affymetrix GeneChip Human Genome U133 Plus 2.0 microarray platform. A longitudinal analysis using paired t-test (p < 0.05 and FC >= 1.5) was applied to identify differentially expressed genes (DEGs) between the two time points followed by ingenuity pathway analysis. Gene Set Enrichment Analysis (GSEA) and quantitative real-time PCR were then performed to verify the microarray results. RESULTS: Gene ontology analysis in neutrophils revealed that response to tocilizumab significantly altered genes regulating mitochondrial dysfunction and oxidative stress (p = 4.6E-05). This was independently verified with GSEA, by identifying a set of oxidative genes whose expression correlated with response to tocilizumab. In PBMC, treatment of sJIA with tocilizumab appeared to affect genes in Oncostatin M signalling and B cell pathways. CONCLUSIONS: For the first time we demonstrate that neutrophils from sJIA patients responding to tocilizumab showed significantly different changes in gene expression. These data could highlight the importance of mitochondrial genes that modulate oxidative stress in the pathogenesis of sJIA. PMID- 26861864 TI - Single-domain intrabodies against hepatitis C virus core inhibit viral propagation and core-induced NFkappaB activation. AB - Hepatitis C virus (HCV) core plays a key role in viral particle formation and is involved in viral pathogenesis. Here, constructs for single-domain intrabodies consisting of variable regions derived from mouse mAbs against HCV core were established. Expressed single-domain intrabodies were shown to bind to HCV core, and inhibit the growth of cell culture-produced HCV derived from JFH-1 (genotype 2a) and a TH (genotype 1b)/JFH-1 chimera. Adenovirus vectors expressing intrabodies were also capable of reducing HCV propagation. Intrabody expression did not affect viral entry or genome replication of single-round infectious trans complemented HCV particles. However, intrabody expression reduced intracellular and extracellular infectious titres in CD81-defective Huh7-25 cells transfected with the HCV genome, suggesting that these intrabodies impair HCV assembly. Furthermore, intrabody expression suppressed HCV core-induced NFkappaB promoter activity. These intrabodies may therefore serve as tools for elucidating the role of core in HCV pathogenesis. PMID- 26861865 TI - Randomised controlled trial to evaluate the efficacy and usability of a computerised phone-based lifestyle coaching system for primary and secondary prevention of stroke. AB - BACKGROUND: One of the most effective current approaches to preventing stroke events is the reduction of lifestyle risk factors, such as unhealthy diet, physical inactivity and smoking. In this study, we assessed the efficacy and usability of the phone-based Computer-aided Prevention System (CAPSYS) in supporting the reduction of lifestyle-related risk factors. METHODS: A single centre two-arm clinical trial was performed between January 2013 and February 2014, based on individual follow-up periods of six months with 94 patients at high risk of stroke, randomly assigned to an intervention group (IC: 48; advised to use the CAPSYS system) or a standard care group (SC: 46). Study parameters, such as blood pressure, blood values (HDL, LDL, HbA1c, glycaemia and triglycerides), weight, height, physical activity as well as nutrition and smoking habits were captured through questionnaires and medical records at baseline and post-intervention and analysed to detect significant changes. The usability of the intervention was assessed based on the standardised System Usability Scale (SUS) complemented by a more system-specific user satisfaction and feedback questionnaire. RESULTS: The statistical evaluation of primary measures revealed significant decreases of systolic blood pressure (mean of the differences = -9 mmHg; p = 0.03; 95% CI = [-17.29, -0.71]), LDL (pseudo-median of the differences = -7.9 mg/dl; p = 0.04; 95% CI = [-18.5, -0.5]) and triglyceride values (pseudo-median of the differences = -12.5 mg/dl; p = 0.04; 95% CI = [-26, 0.5]) in the intervention group, while no such changes could be observed in the control group. Furthermore, we detected a statistically significant increase in self-reported fruit and vegetable consumption (pseudo-median of the differences = 5.4 servings/week; p = 0.04; 95% CI = [0.5, 10.5]) and a decrease in sweets consumption (pseudo-median of the differences = -2 servings/week; p = 0.04; 95% CI = [-4, -0.00001]) in the intervention group. The usability assessment showed that the CAPSYS system was, in general, highly accepted by the users (average SUS score: 80.1). CONCLUSIONS: The study provided encouraging results indicating that a computerised phone-based lifestyle coaching system, such as CAPSYS, can support the usual treatment in reducing cerebro-cardiovascular risk factors and that such an approach is well applicable in practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02444715. PMID- 26861866 TI - Nurses in Supportive Housing are Associated With Decreased Health Care Utilization and Improved HIV Biomarkers in Formerly Homeless Adults. AB - A San Francisco study conducted in 2008 showed that the permanent supportive housing program, Direct Access to Housing, dramatically decreased the risk of death in people living with HIV. In our study, we compared the health care utilization patterns and HIV-related biological markers of formerly homeless adults with HIV before and during two types of permanent supportive housing: (a) housing with on-site nursing care for residents, and (b) housing without on-site nursing care. Using nearest-neighbor matching with propensity scoring, the difference in outcomes was calculated. In the matched analysis, adjusted for adherence to combination antiretroviral therapy, people housed at sites with nurses had 4.8 fewer emergency department visits per person (SE: 1.53, p < .01), and they had an increased mean CD4+ T cell count (101.14 cells per person [SE: 55.10, p < .05]) compared to those who lived at sites without nurses. PMID- 26861868 TI - Structure of Sphingolipids From Sea Cucumber Cucumaria frondosa and Structure Specific Cytotoxicity Against Human HepG2 Cells. AB - To investigate the relationship between structure and activity, three glucocerebroside series (CFC-1, CFC-2 and CFC-3), ceramides (CF-Cer) and long chain bases (CF-LCB) of sea cucumber Cucumaria frondosa (C. frondosa) were isolated and evaluated in HepG2 cells. The molecular species of CFC-1, CFC-2 and CFC-3 and CF-Cer were identified using reversed-phase liquid chromatography with heated electrospray ionization coupled to high-resolution mass spectrometry (RPLC HESI-HRMS), and determined on the basis of chemical and spectroscopic evidence: For the three glucocerebroside series, fatty acids (FA) were mainly saturated (18:0 and 22:0), monounsaturated (22:1, 23:1 and 24:1) and 2-hydroxyl FA (2-HFA) (23:1 h and 24:1 h), the structure of long-chain bases (LCB) were dihydroxy (d17:1, d18:1 and d18:2) and trihydroxy (t16:0 and t17:0), and the glycosylation was glucose; For CF-Cer, FA were primarily saturated (17:0) and monounsaturated (16:1 and 19:1), the structure of LCB were dihydroxy (d17:1 and d18:1), and trihydroxy (t16:0). The results of cell experiment indicated that all of three glucocerebroside series, CF-Cer and CF-LCB exhibited an inhibitory effects on cell proliferation. Moreover, CFC-3 was most effective in three glucocerebrosides to HepG-2 cell viability. The inhibition effect of CF-LCB was the strongest, and the inhibition effect of CF-Cer was much stronger than glucocerebrosides. PMID- 26861869 TI - Increased expression of dermatopontin and its implications for testicular dysfunction in mice. AB - An array of specific and non-specific molecules, which are expressed in the testis, have been demonstrated to be responsible for testicular function. Our previous study revealed that dermatopontin (DPT) is expressed in Sertoli cells of the testis, however, its roles in testicular function remains somewhat elusive. In the present study, CdCl2- and busulfan-induced testicular dysfunction models were used to investigate the implications of DPT expression for testicular function. The mRNA and protein expression levels of DPT were detected using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. A negative correlation was observed between testicular damage and the expression of DPT, which suggested that an increase in DPT expression may be a marker for testicular dysfunction. This result was corroborated by the finding that transgenic mice exhibiting Sertoli cell-specific overexpression of DPT exhibited damage to their testicular morphology. Additionally, DPT overexpression in the testis affected the expression levels of claudin-11 and zonula occludens-1, which indicated that DPT may affect testicular function by affecting the integrity of the blood-testis barrier (BTB). In conclusion, the present study provided evidence to suggest that DPT may be indicative of mouse testicular dysfunction, since increased expression may be associated with damage to the BTB. PMID- 26861871 TI - 25 Years of the Journal of Fluorescence. PMID- 26861867 TI - Risk factors for COPD exacerbations in inhaled medication users: the COPDGene study biannual longitudinal follow-up prospective cohort. AB - BACKGROUND: Despite inhaled medications that decrease exacerbation risk, some COPD patients experience frequent exacerbations. We determined prospective risk factors for exacerbations among subjects in the COPDGene Study taking inhaled medications. METHODS: 2113 COPD subjects were categorized into four medication use patterns: triple therapy with tiotropium (TIO) plus long-acting beta agonist/inhaled-corticosteroid (ICS +/- LABA), tiotropium alone, ICS +/- LABA, and short-acting bronchodilators. Self-reported exacerbations were recorded in telephone and web-based longitudinal follow-up surveys. Associations with exacerbations were determined within each medication group using four separate logistic regression models. A head-to-head analysis compared exacerbation risk among subjects using tiotropium vs. ICS +/- LABA. RESULTS: In separate logistic regression models, the presence of gastroesophageal reflux, female gender, and higher scores on the St. George's Respiratory Questionnaire were significant predictors of exacerbator status within multiple medication groups (reflux: OR 1.62-2.75; female gender: OR 1.53 - OR 1.90; SGRQ: OR 1.02-1.03). Subjects taking either ICS +/- LABA or tiotropium had similar baseline characteristics, allowing comparison between these two groups. In the head-to-head comparison, tiotropium users showed a trend towards lower rates of exacerbations (OR = 0.69 [95 % CI 0.45, 1.06], p = 0.09) compared with ICS +/- LABA users, especially in subjects without comorbid asthma (OR = 0.56 [95% CI 0.31, 1.00], p = 0.05). CONCLUSIONS: Each common COPD medication usage group showed unique risk factor patterns associated with increased risk of exacerbations, which may help clinicians identify subjects at risk. Compared to similar subjects using ICS +/- LABA, those taking tiotropium showed a trend towards reduced exacerbation risk, especially in subjects without asthma. TRIAL REGISTRATION: ClinicalTrials.gov NCT00608764, first received 1/28/2008. PMID- 26861870 TI - [New oral anticoagulants for prophylaxis of stroke. Results of an expert conference on practical use in geriatric patients]. AB - Geriatric patients with non-valvular atrial fibrillation (AF) are increasingly being treated with novel oral anticoagulants (NOAC) to prevent ischemic stroke. This article highlights the outcome of an expert meeting on the practical use of NOAC in elderly patients. An interdisciplinary group of experts discussed the current situation of stroke prevention in geriatric patients and its practical management in daily clinical practice. The topic was examined through focused impulse presentations and critical analyses as the basis for the expert consensus. The key issues are summarized in this paper. The European Society of Cardiology (ESC) guidelines from 2012 for the management of patients with non valvular AF recommend NOAC as the preferred treatment and vitamin K antagonists (VKA) only as an alternative option. Currently, the NOAC factor Xa inhibitors apixaban and rivaroxaban and the thrombin inhibitor dabigatran are more commonly used in clinical practice for patients with AF. Although these drugs have many similarities and are often grouped together it is important to recognize that the pharmacology and dose regimes differ between compounds. Especially n elderly patients NOAC drugs have some advantages compared to VKA, e.g. less drug-drug interactions with concomitant medication and a more favorable risk-benefit ratio mostly driven by the reduction of bleeding. Treatment of anticoagulation in geriatric patients requires weighing the serious risk of stroke against an equally high risk of major bleeding and pharmacoeconomic considerations. Geriatric patients in particular have the greatest benefit from NOAC, which can also be administered in cases of reduced renal function. Regular control of the indications is indispensable, as also for all other medications of the patient. The use of NOAC should certainly not be withheld from geriatric patients who have a clear need for oral anticoagulation. PMID- 26861873 TI - Identification and Characterization of IgdE, a Novel IgG-degrading Protease of Streptococcus suis with Unique Specificity for Porcine IgG. AB - Streptococcus suisis a major endemic pathogen of pigs causing meningitis, arthritis, and other diseases. ZoonoticS. suisinfections are emerging in humans causing similar pathologies as well as severe conditions such as toxic shock-like syndrome. Recently, we discovered an IdeS family protease ofS. suisthat exclusively cleaves porcine IgM and represents the first virulence factor described, linkingS. suisto pigs as their natural host. Here we report the identification and characterization of a novel, unrelated protease ofS. suisthat exclusively targets porcine IgG. This enzyme, designated IgdE forimmunoglobulinG degradingenzyme ofS. suis, is a cysteine protease distinct from previous characterized streptococcal immunoglobulin degrading proteases of the IdeS family and mediates efficient cleavage of the hinge region of porcine IgG with a high degree of specificity. The findings that allS. suisstrains investigated possess the IgG proteolytic activity and that piglet serum samples contain specific antibodies against IgdE strongly indicate that the protease is expressedin vivoduring infection and represents a novel and putative important bacterial virulence/colonization determinant, and a thus potential therapeutic target. PMID- 26861872 TI - Investigating the Sensitivity of NAD+-dependent Sirtuin Deacylation Activities to NADH. AB - Protein lysine posttranslational modification by an increasing number of different acyl groups is becoming appreciated as a regulatory mechanism in cellular biology. Sirtuins are class III histone deacylases that use NAD(+)as a co-substrate during amide bond hydrolysis. Several studies have described the sirtuins as sensors of the NAD(+)/NADH ratio, but it has not been formally tested for all the mammalian sirtuinsin vitro To address this problem, we first synthesized a wide variety of peptide-based probes, which were used to identify the range of hydrolytic activities of human sirtuins. These probes included aliphatic epsilon-N-acyllysine modifications with hydrocarbon lengths ranging from formyl (C1) to palmitoyl (C16) as well as negatively charged dicarboxyl derived modifications. In addition to the well established activities of the sirtuins, "long chain" acyllysine modifications were also shown to be prone to hydrolytic cleavage by SIRT1-3 and SIRT6, supporting recent findings. We then tested the ability of NADH, ADP-ribose, and nicotinamide to inhibit these NAD(+) dependent deacylase activities of the sirtuins. In the commonly used 7-amino-4 methylcoumarin-coupled fluorescence-based assay, the fluorophore has significant spectral overlap with NADH and therefore cannot be used to measure inhibition by NADH. Therefore, we turned to an HPLC-MS-based assay to directly monitor the conversion of acylated peptides to their deacylated forms. All tested sirtuin deacylase activities showed sensitivity to NADH in this assay. However, the inhibitory concentrations of NADH in these assays are far greater than the predicted concentrations of NADH in cells; therefore, our data indicate that NADH is unlikely to inhibit sirtuinsin vivo These data suggest a re-evaluation of the sirtuins as direct sensors of the NAD(+)/NADH ratio. PMID- 26861874 TI - Transient Expression of Fez Family Zinc Finger 2 Protein Regulates the Brn3b Gene in Developing Retinal Ganglion Cells. AB - Retinal ganglion cells (RGCs) are projection neurons in the neural retina that relay visual information from the environment to the central nervous system. The early expression of MATH5 endows the post-mitotic precursors with RGC competence and leads to the activation ofBrn3bthat marks committed RGCs. Nevertheless, this fate commitment process and, specifically, regulation ofBrn3bremain elusive. To explore the molecular mechanisms underlying RGC generation in the mouse retina, we analyzed the expression and function of Fez family zinc finger 2 (FEZF2), a transcription factor critical for the development of projection neurons in the cerebral cortex.Fezf2mRNA and protein were transiently expressed at embryonic day 16.5 in the inner neuroblast layer and the prospective ganglion cell layer of the retina, respectively. Knockout ofFezf2in the developing retina reduced BRN3B+ cells and increased apoptotic cell markers.Fezf2knockdown by retinalin uteroelectroporation diminished BRN3B but not the coexpressed ISLET1 and BRN3A, indicating that the BRN3B decrease was the cause, not the result, of the overall reduction of BRN3B+ RGCs in theFezf2knockout retina. Moreover, the mRNA and promoter activity ofBrn3bwere increasedin vitroby FEZF2, which bound to a 5' regulatory fragment in theBrn3bgenomic locus. These results indicate that transient expression ofFezf2in the retina modulates the transcription ofBrn3band the survival of RGCs. This study improves our understanding of the transcriptional cascade required for the specification of RGCs and provides novel insights into the molecular basis of retinal development. PMID- 26861875 TI - The Endoplasmic Reticulum Chaperone Calnexin Is a NADPH Oxidase NOX4 Interacting Protein. AB - Within the family of NADPH oxidases, NOX4 is unique as it is predominantly localized in the endoplasmic reticulum, has constitutive activity, and generates hydrogen peroxide (H2O2). We hypothesize that these features are consequences of a so far unidentified NOX4-interacting protein. Two-dimensional blue native (BN) electrophorese combined with SDS-PAGE yielded NOX4 to reside in macromolecular complexes. Interacting proteins were screened by quantitative SILAC (stable isotope labeling of amino acids in cell culture) co-immunoprecipitation (Co-IP) in HEK293 cells stably overexpressing NOX4. By this technique, several interacting proteins were identified with calnexin showing the most robust interaction. Calnexin also resided in NOX4-containing complexes as demonstrated by complexome profiling from BN-PAGE. The calnexin NOX4 interaction could be confirmed by reverse Co-IP and proximity ligation assay, whereas NOX1, NOX2, or NOX5 did not interact with calnexin. Calnexin deficiency as studied in mouse embryonic fibroblasts from calnexin(-/-)mice or in response to calnexin shRNA reduced cellular NOX4 protein expression and reactive oxygen species formation. Our results suggest that endogenous NOX4 forms macromolecular complexes with calnexin, which are needed for the proper maturation, processing, and function of NOX4 in the endoplasmic reticulum. PMID- 26861877 TI - Organophosphate Hydrolase Is a Lipoprotein and Interacts with Pi-specific Transport System to Facilitate Growth of Brevundimonas diminuta Using OP Insecticide as Source of Phosphate. AB - Organophosphate hydrolase (OPH), encoded by the organophosphate degradation (opd) island, hydrolyzes the triester bond found in a variety of organophosphate insecticides and nerve agents. OPH is targeted to the inner membrane ofBrevundimonas diminutain a pre-folded conformation by thetwinargininetransport (Tat) pathway. The OPH signal peptide contains an invariant cysteine residue at the junction of the signal peptidase (Spase) cleavage site along with a well conserved lipobox motif. Treatment of cells producing native OPH with the signal peptidase II inhibitor globomycin resulted in accumulation of most of the pre-OPH in the cytoplasm with negligible processed OPH detected in the membrane. Substitution of the conserved lipobox cysteine to serine resulted in release of OPH into the periplasm, confirming that OPH is a lipoprotein. Analysis of purified OPH revealed that it was modified with the fatty acids palmitate and stearate. Membrane-bound OPH was shown to interact with the outer membrane efflux protein TolC and with PstS, the periplasmic component of the ABC transporter complex (PstSACB) involved in phosphate transport. Interaction of OPH with PstS appears to facilitate transport of Pigenerated from organophosphates due to the combined action of OPH and periplasmically located phosphatases. Consistent with this model,opdnull mutants ofB. diminutafailed to grow using the organophosphate insecticide methyl parathion as sole source of phosphate. PMID- 26861878 TI - Elongation of the Poly-gamma-glutamate Tail of F420 Requires Both Domains of the F420:gamma-Glutamyl Ligase (FbiB) of Mycobacterium tuberculosis. AB - Cofactor F420is an electron carrier with a major role in the oxidoreductive reactions ofMycobacterium tuberculosis, the causative agent of tuberculosis. A gamma-glutamyl ligase catalyzes the final steps of the F420biosynthesis pathway by successive additions ofl-glutamate residues to F420-0, producing a poly-gamma glutamate tail. The enzyme responsible for this reaction in archaea (CofE) comprises a single domain and produces F420-2 as the major species. The homologousM. tuberculosisenzyme, FbiB, is a two-domain protein and produces F420with predominantly 5-7l-glutamate residues in the poly-gamma-glutamate tail. The N-terminal domain of FbiB is homologous to CofE with an annotated gamma glutamyl ligase activity, whereas the C-terminal domain has sequence similarity to an FMN-dependent family of nitroreductase enzymes. Here we demonstrate that full-length FbiB adds multiplel-glutamate residues to F420-0in vitroto produce F420-5 after 24 h; communication between the two domains is critical for full gamma-glutamyl ligase activity. We also present crystal structures of the C terminal domain of FbiB in apo-, F420-0-, and FMN-bound states, displaying distinct sites for F420-0 and FMN ligands that partially overlap. Finally, we discuss the features of a full-length structural model produced by small angle x ray scattering and its implications for the role of N- and C-terminal domains in catalysis. PMID- 26861876 TI - Reduced Ets Domain-containing Protein Elk1 Promotes Pulmonary Fibrosis via Increased Integrin alphavbeta6 Expression. AB - Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with high mortality. Active TGFbeta1 is considered central to the pathogenesis of IPF. A major mechanism of TGFbeta1 activation in the lung involves the epithelially restricted alphavbeta6 integrin. Expression of the alphavbeta6 integrin is dramatically increased in IPF. How alphavbeta6 integrin expression is regulated in the pulmonary epithelium is unknown. Here we identify a region in the beta6 subunit gene (ITGB6) promoter acting to markedly repress basal gene transcription, which responds to both the Ets domain-containing protein Elk1 (Elk1) and the glucocorticoid receptor (GR). Both Elk1 and GR can regulate alphavbeta6 integrin expression in vitro We demonstrate Elk1 binding to the ITGB6 promoter basally and that manipulation of Elk1 or Elk1 binding alters ITGB6 promoter activity, gene transcription, and alphavbeta6 integrin expression. Crucially, we find that loss of Elk1 causes enhanced Itgb6 expression and exaggerated lung fibrosis in an in vivo model of fibrosis, whereas the GR agonist dexamethasone inhibits Itgb6 expression. Moreover, Elk1 dysregulation is present in epithelium from patients with IPF. These data reveal a novel role for Elk1 regulating ITGB6 expression and highlight how dysregulation of Elk1 can contribute to human disease. PMID- 26861879 TI - Co-immunoprecipitation with Tau Isoform-specific Antibodies Reveals Distinct Protein Interactions and Highlights a Putative Role for 2N Tau in Disease. AB - Alternative splicing generates multiple isoforms of the microtubule-associated protein Tau, but little is known about their specific function. In the adult mouse brain, three Tau isoforms are expressed that contain either 0, 1, or 2 N terminal inserts (0N, 1N, and 2N). We generated Tau isoform-specific antibodies and performed co-immunoprecipitations followed by tandem mass tag multiplexed quantitative mass spectrometry. We identified novel Tau-interacting proteins of which one-half comprised membrane-bound proteins, localized to the plasma membrane, mitochondria, and other organelles. Tau was also found to interact with proteins involved in presynaptic signal transduction. MetaCore analysis revealed one major Tau interaction cluster that contained 33 Tau pulldown proteins. To explore the pathways in which these proteins are involved, we conducted an ingenuity pathway analysis that revealed two significant overlapping pathways, "cell-to-cell signaling and interaction" and "neurological disease." The functional enrichment tool DAVID showed that in particular the 2N Tau-interacting proteins were specifically associated with neurological disease. Finally, for a subset of Tau interactions (apolipoprotein A1 (apoA1), apoE, mitochondrial creatine kinase U-type, beta-synuclein, synaptogyrin-3, synaptophysin, syntaxin 1B, synaptotagmin, and synapsin 1), we performed reverse co-immunoprecipitations, confirming the preferential interaction of specific isoforms. For example, apoA1 displayed a 5-fold preference for the interaction with 2N, whereas beta-synuclein showed preference for 0N. Remarkably, a reverse immunoprecipitation with apoA1 detected only the 2N isoform. This highlights distinct protein interactions of the different Tau isoforms, suggesting that they execute different functions in brain tissue. PMID- 26861881 TI - Identification of Unintuitive Features of Sumoylation through Mathematical Modeling. AB - Sumoylation is a multistep, multienzymatic post-translational modification in which a small ubiquitin-like modifier protein (SUMO) is attached to the target. We present the first mathematical model for sumoylation including enzyme mechanism details such as autosumoylation of E2 and multifunctional nature of SENP. Simulations and analysis reveal three nonobvious properties for the long term response, modeled as an open system: (i) the steady state sumoylation level is robust to variation in several enzyme properties; (ii) even when autosumoylation of E2 results in equal or higher activity, the target sumoylation levels are lower; and (iii) there is an optimal SENP concentration at which steady state target sumoylation level is maximum. These results are qualitatively different for a short term response modeled as a closed system, where e.g. sumoylation always decreases with increasing SENP levels. Simulations with multiple targets suggest that the available SUMO is limiting, indicating a possible explanation for the experimentally observed low fractional sumoylation. We predict qualitative differences in system responses at short post translational and longer transcriptional time scales. We thus use this mechanism based model to explain system properties and generate testable hypotheses for existence and mechanism of unexpected responses. PMID- 26861880 TI - Pro-recombination Role of Srs2 Protein Requires SUMO (Small Ubiquitin-like Modifier) but Is Independent of PCNA (Proliferating Cell Nuclear Antigen) Interaction. AB - Srs2 plays many roles in DNA repair, the proper regulation and coordination of which is essential. Post-translational modification by small ubiquitin-like modifier (SUMO) is one such possible mechanism. Here, we investigate the role of SUMO in Srs2 regulation and show that the SUMO-interacting motif (SIM) of Srs2 is important for the interaction with several recombination factors. Lack of SIM, but not proliferating cell nuclear antigen (PCNA)-interacting motif (PIM), leads to increased cell death under circumstances requiring homologous recombination for DNA repair. Simultaneous mutation of SIM in asrs2DeltaPIMstrain leads to a decrease in recombination, indicating a pro-recombination role of SUMO. Thus SIM has an ambivalent function in Srs2 regulation; it not only mediates interaction with SUMO-PCNA to promote the anti-recombination function but it also plays a PCNA-independent pro-recombination role, probably by stimulating the formation of recombination complexes. The fact that deletion of PIM suppresses the phenotypes of Srs2 lacking SIM suggests that proper balance between the anti-recombination PCNA-bound and pro-recombination pools of Srs2 is crucial. Notably, sumoylation of Srs2 itself specifically stimulates recombination at the rDNA locus. PMID- 26861884 TI - Is treatment for alcohol use disorder associated with reductions in criminal offending? A national data linkage cohort study in England. AB - BACKGROUND: This is the first English national study of change in criminal offending following treatment for alcohol use disorder (AUD). METHODS: All adults treated for AUD by all publicly funded treatment services during April 2008-March 2009 (n=53,017), with data linked to the Police National Computer (April 2006 November 2011). Pre-treatment offender sub-populations were identified by Latent Profile Analysis. The outcome measure was the count of recordable criminal offences during two-year follow-up after admission. A mixed-effects, Poisson regression modelled outcome, adjusting for demographics and clinical information, the latent classes, and treatment exposure covariates. RESULTS: Twenty-two percent of the cohort committed one or more offences in the two years pre treatment (n=11,742; crude rate, 221.5 offenders per 1000). During follow-up, the number of offenders and offences fell by 23.5% and 24.0%, respectively (crude rate, 69.4 offenders per 1000). During follow-up, a lower number of offences was associated with: completing treatment (adjusted incident rate ratio [IRR] 0.82; 95% confidence interval [CI] 0.79-0.85); receiving inpatient detoxification (IRR 0.84; CI 0.80-0.89); or community pharmacological therapy (IRR 0.89; CI 0.84 0.96). Reconviction was reduced in the sub-population characterised by driving offences (n=1,140; 11.7%), but was relatively high amongst acquisitive (n=768; 58.3% reconvicted) and violent offending sub-populations (n=602; 77.6% reconvicted). CONCLUSIONS: Reduced offending was associated with successful completion of AUD treatment and receiving inpatient and pharmacological therapy, but not enrolment in psychological and residential interventions. Treatment services (particularly those providing psychological therapy and residential care) should be alert to offending, especially violent and acquisitive crime, and enhance crime reduction interventions. PMID- 26861882 TI - High Resolution Structures of Periplasmic Glucose-binding Protein of Pseudomonas putida CSV86 Reveal Structural Basis of Its Substrate Specificity. AB - Periplasmic substrate-binding proteins (SBPs) bind to the specific ligand with high affinity and mediate their transport into the cytoplasm via the cognate inner membrane ATP-binding cassette proteins. Because of low sequence identities, understanding the structural basis of substrate recognition by SBPs has remained very challenging. There are several structures available for the ligand-bound sugar SBPs, but very few unliganded structures are reported. No structural data are available for sugar SBPs fromPseudomonassp. to date. This study reports the first high resolution crystal structures of periplasmic glucose-binding protein fromPseudomonas putidaCSV86 (ppGBP) in unliganded form (2.5 A) and complexed with glucose (1.25 A) and galactose (1.8 A). Asymmetric domain closure of ppGBP was observed upon substrate binding. The ppGBP was found to have an affinity of ~ 0.3 MUmfor glucose. The structural analysis showed that the sugars are bound to the protein mainly by hydrogen bonds, and the loss of two strong hydrogen bonds between ppGBP and galactose compared with glucose may be responsible for lowering its affinity toward galactose. The higher stability of ppGBP-glucose complex was also indicated by an 8 degrees C increase in the melting temperature compared with unliganded form and ppGBP-galactose complex. ppGBP binds to monosaccharide, but the structural features revealed it to have an oligosaccharide-binding protein fold, indicating that during evolution the sugar binding pocket may have undergone structural modulation to accommodate monosaccharide only. PMID- 26861883 TI - Risk of mortality and physiologic injury evident with lower alcohol exposure among HIV infected compared with uninfected men. AB - BACKGROUND: HIV infected (HIV+) individuals may be more susceptible to alcohol related harm than uninfected individuals. METHODS: We analyzed data on HIV+ and uninfected individuals in the Veterans Aging Cohort Study (VACS) with an Alcohol Use Disorders Identification Test-Consumption AUDIT-C score from 2008 to 2012. We used Cox proportional hazards models to examine the association between alcohol exposure and mortality through July, 2014; and linear regression models to assess the association between alcohol exposure and physiologic injury based on VACS Index Scores. Models were adjusted for age, race/ethnicity, smoking, and hepatitis C infection. RESULTS: The sample included 18,145 HIV+ and 42,228 uninfected individuals. Among HIV+ individuals, 76% had undetectable HIV-1 RNA (<500 copies/ml). The threshold for an association of alcohol use with mortality and physiologic injury differed by HIV status. Among HIV+ individuals, AUDIT-C score >=4 (hazard ratio [HR] 1.25, 95% CI 1.09-1.44) and >=30 drinks per month (HR, 1.30, 95% CI 1.14-1.50) were associated with increased risk of mortality. Among uninfected individuals, AUDIT-C score >=5 (HR, 1.19, 95% CI 1.07-1.32) and >=70 drinks per month (HR 1.13, 95% CI 1.00-1.28) were associated with increased risk. Similarly, AUDIT-C threshold scores of 5-7 were associated with physiologic injury among HIV+ individuals (beta 0.47, 95% CI 0.22, 0.73) and a score of 8 or more was associated with injury in uninfected (beta 0.29, 95% CI 0.16, 0.42) individuals. CONCLUSIONS: Despite antiretroviral therapy, HIV+ individuals experienced increased mortality and physiologic injury at lower levels of alcohol use compared with uninfected individuals. Alcohol consumption limits should be lower among HIV+ individuals. PMID- 26861885 TI - Health-Related Quality of Life in Patients with Idiopathic Pulmonary Fibrosis. AB - PURPOSE: Idiopathic pulmonary fibrosis (IPF) produces symptoms and activity limitations that impair health-related quality of life (HRQOL). The Patient Reported Outcomes Measurement Information System((r)) (PROMIS((r))) includes measures of self-reported health and HRQOL for a range of conditions. This study evaluated the HRQOL of individuals with IPF using PROMIS measures and examined associations between HRQOL and key symptoms or supplemental oxygen need. METHODS: Individuals who reported being told by a doctor that they have IPF completed an online battery of measures at baseline and 7-10 days later (for test-retest reliability). Measures included a brief survey of demographic and health-related questions, the PROMIS-29 profile, the Modified Medical Research Council Dyspnea Scale (MMRC), PROMIS dyspnea severity short form, A Tool to Assess Quality of life in IPF (ATAQ-IPF) and one cough item from the Functional Assessment of Chronic Illness Therapy (FACIT). RESULTS: 220 individuals were included in the final sample. Except for sleep disturbance, all PROMIS domain scores significantly (p < .01) differed by MMRC level. Supplemental oxygen users were more impaired than non-users in fatigue, physical function, and social role participation (p < 0.01). The test-retest reliability was acceptable to excellent (>0.7) for all scales, but was lower for sleep disturbance (0.64). CONCLUSIONS: People with IPF report substantial deficits in HRQOL across a range of PROMIS domains, and deficits vary by dyspnea and cough severity. These deficits warrant monitoring in clinical practice and consideration when investigating new therapies. Further research is required to further evaluate the psychometric performance of the PROMIS-29 in IPF. PMID- 26861887 TI - Late presentation of a variant of Herlyn-Werner-Wunderlich syndrome. PMID- 26861886 TI - Prognostic factors for recurrence and survival among patients with invasive vulvar Paget disease included in the VULCAN study. AB - OBJECTIVE: To identify prognostic factors associated with recurrence and overall survival among patients with invasive vulvar Paget disease. METHODS: An analysis was conducted of patients with invasive vulvar Paget disease included in VULCAN, an international multicenter retrospective study of patients diagnosed with vulvar cancer between January 1, 2001, and December 31, 2005. Data regarding diagnosis, treatment, and follow-up were obtained from the patients' medical records. Univariate and multivariate analyses were performed. RESULTS: Among 1727 patients registered in the VULCAN database, 38 patients had invasive vulvar Paget disease. The mean follow-up time for these patients was 44.1+/-35.7 months, the overall recurrence rate (local lesions and distant metastases) was 58%, and the mean overall survival time was 58.5+/-0.5 months. Case load at the treating center inversely correlated with local recurrence (P=0.01). Tumor size and FIGO stage were associated with the presence of distant metastases (P<0.001 for both). Adjuvant therapy (radiotherapy or chemotherapy) was associated with a reduced risk of distant metastases and increased overall survival (P<0.001 for both). CONCLUSION: Local recurrences of invasive vulvar Paget disease were associated with the case load at the treating center. Distant recurrences were associated with tumor size and FIGO stage. It is possible that adjuvant radiotherapy or chemotherapy could offer patients benefits by increasing overall survival rates. PMID- 26861888 TI - "It Really Is Not Just Gay, but African American Gay": The Impact of Community and Church on the Experiences of Black Lesbians Living in North Central Florida. AB - The experiences of Black lesbians highlight the unique circumstance found at the intersection of sexuality, race, and gender. However, most sexuality research tends to focus on White lesbians and White gay men, and most race research tends to focus on Black heterosexuals. Furthermore, research on the Black gay community tends to focus on those living in the Northeast or on the West Coast, neglecting experiences of those living in the more politically, socially, and religiously conservative South. This article draws on data obtained from semistructured interviews with 12 Black lesbians living in north central Florida, exploring their perspectives as they negotiate a social world of intersecting oppressions. Participants especially highlight how they contextualized their sexuality in racialized terms and negotiated it in racially defined communities. PMID- 26861889 TI - Readthrough transcription: How are DoGs made and what do they do? AB - In recent years, the realization that most of the genome is transcribed has transformed the study of mammalian gene expression. Much effort has gone into investigating how this pervasive transcription is regulated and what the functions of the resulting transcripts are, if any. We recently discovered that stress-induced transcriptional readthrough generates very long downstream of gene containing transcripts (DoGs), which may explain up to 20% of intergenic transcription. DoGs are induced by osmotic stress at the level of transcription by a mechanism that depends on calcium release from the endoplasmic reticulum mediated by IP3 receptors. Here, we discuss DoG induction and function in the context of the literature, with special focus on 2 outstanding questions. First, we discuss possible molecular mechanisms underlying DoG induction through reduced transcription termination. Second, we explore how DoGs may function in maintaining euchromatin after nuclear scaffold stress. In short, we review important aspects of DoG biogenesis and function, and provide an outlook for continued DoG study. PMID- 26861890 TI - Cluster-Mediated Crossed Bilayer Precision Assemblies of 1D Nanowires. AB - Highly organized crossed bilayer assemblies of nanowires (NWs) are made using directed hydrogen bonding between the protecting ligand shells of atomically precise cluster molecules anchored on NWs. Layers of quantum clusters remain sandwiched between two neighboring NWs at a defined distance, dictated by the core-size of the cluster, while the orientation of the ligands in space dictates the interlayer geometry. PMID- 26861893 TI - Long-Term Pain Reduction Does Not Imply Improved Functional Outcome in Patients Treated With Combined Supraorbital and Occipital Nerve Stimulation for Chronic Migraine. AB - BACKGROUND: Dual supraorbital and occipital nerve stimulation (SONS and ONS) have shown promising efficacy in treating primary headaches. However, its functional outcome is not well studied. OBJECTIVE: To present functional outcome studies of combined SONS and ONS for chronic migraine using verified metrics. METHOD: Consecutive patients with both SONS and ONS assessed with Migraine Disability Assessment (MIDAS) and Beck Depression Index (BDI) both preoperatively and postoperatively were studied. Selected predictor variables included patients with >=50% improvement of pain, disability status, number of years from diagnosis to implantation, and narcotic use. Functional outcome variables included net improvement of ranked MIDAS and BDI scores. Multivariate analysis of variance was performed to assess the correlation between the outcome and predictor variables. RESULTS: Sixteen patients (12 female; average age 52 years old) were studied. Follow-up ranged from 5 to 80 months (average 44.5; sigma = 21.4 months). At most recent follow-up, eight patients had a positive response (>=50% improvement in headache), which was the only predictor of functional outcome (total MIDAS, MIDAS B, and BDI) (p = 0.021). Of note, improvement in functional outcome was only significant during the perioperative 3-6 months period and not throughout long term follow-up. Among the predictor variables, a strong inverse correlation was found between disability status and positive response to stimulation (r = 0.582). CONCLUSION: There is a paucity of studies in quality of life, productivity, and psychosocial aspects with peripheral nerve stimulation therapy for headache. Patients with a positive response to SONS and ONS also reported overall improvement in their functional status as reflected by MIDAS and BDI in the perioperative period. Unfortunately, this effect waned over the long-term follow-up. PMID- 26861894 TI - Evaluating the Persuasiveness of an HIV Mass Communication Campaign Using Gain Framed Messages and Aimed at Creating a Superordinate Identity. AB - This research assesses the coverage and impact of "United Against AIDS," the 2012 2013 Italian National HIV/AIDS prevention campaign to promote safer sex behavior and voluntary HIV counseling and testing. The campaign used gain-framed messages and aimed at creating a superordinate identity. We conducted two studies. The first study employed a quasi-experimental design involving three groups of participants: general population (n = 858), men who have sex with men (MSM; n = 109), and migrants (n = 211). In the second study, we carried out a time-series design to analyze the archival data of the Italian National AIDS Help-Line. Exposure to the campaign was reported by 78.3%, 67.5%, and 57.8% of the general population, MSM, and migrant respondents, respectively. The probability of having unprotected sexual intercourse with multiple partners decreased significantly in the subsample of the general populations that was exposed to the campaign (compared to the nonexposed participants), but the same effect was not found among MSM and migrant participants. The probability of having unprotected sexual intercourse with someone of unknown HIV status decreased after the campaign in the exposed MSM subsample (compared to the nonexposed participants), but the same effect was not found among the general population and migrant participants. In addition, the probability of undertaking HIV testing increased significantly in the exposed participants belonging to the general population but not among MSM and migrant participants. Time-series analysis revealed that the number of calls at the Italian National AIDS Help-Line significantly increased during the campaign. This research provides evidence that the effect of the campaign was complex and varied across participants. PMID- 26861895 TI - Retraction Notice: Generation of Knock down Tools for Transcription Factor 7-like 2 (TCF7L2) and Evaluation of its Expression Pattern in Developing Chicken Optic Tectum. AB - The publishers have decided to retract the manuscript entitled "Generation of Knock Down Tools for Transcription Factor 7-Like-2 (TCF7L2) and Evaluation of its Expression Pattern in Developing Chicken Optic Tectum" published in MicroRNA, volume 4, issue 3, page numbers 209-216, 2015, for the following reasons. * Due to conflict of interests between authors and the Principal Investigator. PMID- 26861891 TI - mGluR2/3 agonist LY379268 rescues NMDA and GABAA receptor level deficits induced in a two-hit mouse model of schizophrenia. AB - RATIONALE: An imbalance of excitatory and inhibitory neurotransmission underlies the glutamate hypothesis of schizophrenia. Agonists of group II metabotropic glutamate receptors, mGluR2/3, have been proposed as novel therapeutic agents to correct this imbalance. However, the influence of mGluR2/3 activity on excitatory and inhibitory neurotransmitter receptors has not been explored. OBJECTIVES: We aimed to investigate the ability of a novel mGluR2/3 agonist, LY379268, to modulate the availability of the excitatory N-methyl-D-aspartate receptor (NMDA R) and the inhibitory gamma-aminobutyrate-A receptor (GABAA-R), in a two-hit mouse model of schizophrenia. METHODS: Wild type (WT) and heterozygous neuregulin 1 transmembrane domain mutant mice (NRG1 HET) were treated daily with phencyclidine (10 mg/kg ip) or saline for 14 days. After a 14-day washout, an acute dose of the mGluR2/3 agonist LY379268 (3 mg/kg), olanzapine (antipsychotic drug comparison, 1.5 mg/kg), or saline was administered. NMDA-R and GABAA-R binding densities were examined by receptor autoradiography in several schizophrenia-relevant brain regions. RESULTS: In both WT and NRG1 HET mice, phencyclidine treatment significantly reduced NMDA-R and GABAA-R binding density in the prefrontal cortex, hippocampus, and nucleus accumbens. Acute treatment with LY379268 restored NMDA-R and GABAA-R levels in the two-hit mouse model comparable to olanzapine. CONCLUSIONS: We demonstrate that the mGluR2/3 agonist LY379268 restores excitatory and inhibitory deficits with similar efficiency as olanzapine in our two-hit schizophrenia mouse model. This study significantly contributes to our understanding of the mechanisms underlying the therapeutic effects of LY379268 and supports the use of agents aimed at mGluR2/3. PMID- 26861892 TI - Impact of partial dopamine depletion on cognitive flexibility in BDNF heterozygous mice. AB - RATIONALE: Cognitive flexibility is a key component of executive function and is disrupted in major psychiatric disorders. Brain-derived neurotrophic factor (BDNF) exerts neuromodulatory effects on synaptic transmission and cognitive/affective behaviors. However, the causal mechanisms linking BDNF hypofunction with executive deficits are not well understood. OBJECTIVES: Here, we assessed the consequences of BDNF hemizygosity on cognitive flexibility in mice performing an operant conditioning task. As dopaminergic-glutamatergic interaction in the striatum is important for cognitive processing, and BDNF heterozygous (BDNF(+/-)) mice display a higher dopamine tone in the dorsal striatum, we also assessed the effects of partial striatal dopamine depletion on task performance and glutamate release. RESULTS: BDNF(+/-) mice acquired discrimination learning as well as new rule learning during set-shifting as efficiently as wild-type mice. However, partial removal of striatal dopaminergic inputs with 6-hydroxydopamine (6-OHDA) impaired these cognitive processes by impeding the maintenance of a new learning strategy in both genotypes. BDNF mutants exhibited performance impairments during reversal learning, and these deficits were associated with increased perseveration to the previously acquired strategy. Partial dopamine depletion of the striatum reversed these cognitive impairments. Additionally, reduction in depolarization-evoked glutamate release noted in the dorsal striatum of BDNF(+/-) mice was not observed in 6-OHDA-infused BDNF mutants indicating normalization of glutamatergic transmission in these animals. CONCLUSIONS: Our data illustrate that BDNF signaling regulates cognitive control processes presumably by maintaining striatal dopamine-glutamate balance. Moreover, aberrations in BDNF signaling may act as a common neurobiological substrate that accounts for executive dysfunction observed in multiple psychiatric conditions. PMID- 26861897 TI - Intra-Household Nutritional Dynamics: A Cross-Sectional Study of Maasai Communities in Kenya. AB - To date, research on dietary consumption and nutritional outcomes of the Maasai in Kenya have failed to explore how gender dynamics and intra-household bargaining power affect dietary decisions. This exploratory qualitative study investigates the decision-making processes regarding eating habits and health seeking behavior within Maasai families in Kenya, and how such roles currently support or conflict with maternal and child health (MCH) program activities in the field of nutritional education and practices. The data were collected from the three group ranches in Laikipia County in Kenya and draws on six focus group discussions with a total of 24 Maasai men and 24 Maasai women. Our research has documented that the dietary and health-seeking decisions of Maasai families are influenced by complex intra- and extra-household factors. Programmatic interventions need to examine decision-making processes within the context of multi-generational family dynamics and gender hierarchies to scale up community driven interventions to ensure sustained behavior change. PMID- 26861896 TI - High-Potency Topical Steroids: An Effective Therapy for Chronic Scalp Inflammation in Rapp-Hodgkin Ectodermal Dysplasia. AB - Chronic erosive pustular dermatitis with a predilection for the scalp is a hallmark of ectodermal dysplasias (EDs) caused by mutations in TP63, including Rapp-Hodgkin and Hay-Wells EDs. It is among the most troublesome and symptomatic complications and is typically refractory to classic wound care approaches. We report two cases of Rapp-Hodgkin ED with refractory scalp erosions that markedly improved with the use of potent topical steroids. We also note marked similarities between this scalp inflammation and "erosive pustular dermatosis of the scalp," a condition more typically found in elderly individuals with severe scalp sun damage, and speculate about possible shared pathogenetic mechanisms. PMID- 26861898 TI - Connections Between Prenatal Physical Activity and Breastfeeding Decisions. AB - Women who engage in prenatal physical activity give themselves, and their child, an advantage over women who did not engage in prenatal physical activity; not only are there significant health benefits for mothers, but there are also great benefits for the unborn child. Breastfeeding is another important decision parents make that can affect the mother and her child. There has been extensive research on the benefits of both prenatal physical activity and breastfeeding, but the connection between the two is unclear. The purpose of this grounded theory article was to identify potential connections between factors influencing women's decisions to engage in prenatal physical activity and breastfeeding among mothers in a medium-sized city in Tennessee. Responses from mothers revealed numerous themes related to both prenatal physical activity and breastfeeding. Connections between prenatal physical activity and breastfeeding, in addition to an overarching theme that captured the women's collective experience, were identified. PMID- 26861899 TI - Skeletal Implications of Chronic Obstructive Pulmonary Disease. AB - Chronic obstructive pulmonary disease (COPD) is associated with numerous comorbidities, among which osteoporosis is of high significance. Low bone mass and the occurrence of fragility fractures is a common finding in patients with COPD. Typical risk factors related directly or indirectly to these skeletal complications include systemic inflammation, tobacco smoking, vitamin D deficiency, and treatment with oral or inhaled corticosteroids. In particular, treatment with glucocorticoids appears to be a strong contributor to bone changes in COPD, but does not fully account for all skeletal complications. Additional to the effects of COPD on bone mass, there is evidence for COPD-related changes in bone microstructure and material properties. This review summarizes the clinical outcomes of low bone mass and increased fracture risk, and reports on recent observations in bone tissue and material in COPD patients. PMID- 26861900 TI - Disease prevalence in a rural Andean population of central Peru: a focus on autoimmune and allergic diseases. AB - INTRODUCTION: The hygiene hypothesis, formulated to explain the increased incidence of allergic and autoimmune diseases observed in industrialized countries, remains controversial. We reflected upon this hypothesis during a medical mission to rural and impoverished villages of central Peru. MATERIALS AND METHODS: The mission was carried out in July 2015 to aid three Andean villages located near Cusco, and comprised 10 American physicians, 4 nurses, and 24 students. After recording the vital signs, patients were triaged by nurses based on the major complaint, visited by physicians, and prescribed medications. Physicians wrote their notes on a one-page form and established diagnoses purely on clinical grounds, without laboratory or imaging testing. Physician notes were then analyzed retrospectively in a de-identified and double-blinded fashion. RESULTS: A total of 1075 patients (357 men and 718 women) were visited during 5 consecutive clinic days, 840 being adults and 235 <18 years of age. The most common complaints were back pain, stomach pain, headache, and vision loss. Osteoarthritis, gastritis, visual disturbances, and parasitic infections dominated the diagnostic categories. Thirty-seven patients (3 %) were diagnosed with an allergic or autoimmune disease, mainly represented by asthma, rheumatoid arthritis, and Hashimoto's thyroiditis, a prevalence that was not significantly lower than that reported in industrialized countries. CONCLUSIONS: Although a study of this nature cannot definitively support or refute the hygiene hypothesis, it does provide a novel snapshot of disease prevalence in rural Andean villages of central Peru. The study could serve as a basis to implement basic public health interventions and prepare for future missions to the same or comparable regions. PMID- 26861901 TI - Peripheral plasma vitamin D and non-HDL cholesterol reflect the severity of cerebral cavernous malformation disease. AB - AIM: To correlate cerebral cavernous malformations (CCMs) disease aggressiveness with peripheral blood biomarkers hypothesized mechanistically. PATIENTS & METHODS: A prospective case-control study enrolled 43 CCM patients, where 25-(OH) vitamin D, HDL and non-HDL cholesterol, CRP plasma levels and leukocyte ROCK activity were correlated with parameters of disease aggressiveness reflecting chronic and acute domains. RESULTS: Patients with one or more features of chronically aggressive disease (early age at symptom onset, two or more symptomatic bleeds, high lesion burden) had significantly lower 25-(OH) vitamin D and non-HDL cholesterol levels in comparison to patients without these features. CONCLUSION: Validation of these biomarkers and their potential treatment modulation may influence the clinical care of patients with CCM disease. PMID- 26861903 TI - Auditory hallucinations preceding migraine, differentiation with epileptic origin: A case report. PMID- 26861902 TI - Variations in IL-23 and IL-25 receptor gene structure, sequence and expression associated with the two disease forms of sheep paratuberculosis. AB - The immunopathology of paucibacillary and multibacillary sheep paratuberculosis is characterized by inflammatory T cell and macrophage responses respectively. IL 23 and IL-25 are key to the development of these responses by interaction with their complex receptors, IL-23R/IL-12RB1 and IL-17RA/IL-17RB. In humans, variations in structure, sequence and/or expression of these genes have been implicated in the different pathological forms of tuberculosis and leprosy, and in gastrointestinal inflammatory disorders such as Crohn's disease. Sequencing has identified multiple transcript variants of sheep IL23R, IL12RB1 and IL17RB and a single IL17RA transcript. RT-qPCR assays were developed for all the identified variants and used to compare expression in the ileo-caecal lymph node of sheep with paucibacillary or multibacillary paratuberculosis and uninfected animals. With IL-23 receptor, only the IL12RB1v3 variant, which lacks the receptor activation motif was differentially expressed and was significantly increased in multibacillary disease; this may contribute to high Th2 responses. Of the IL17RB variants only full length IL17RB was differentially expressed and was significantly increased in multibacillary pathology; which may also contribute to Th2 polarization. IL17RA expression was significantly increased in paucibacillary disease. The contrast between the IL17RA and IL17RB results may indicate that, in addition to Th1 cells, Th17 T cells are also involved in paucibacillary pathology. PMID- 26861904 TI - Erratum to: Integrated EpCAM-independent subtraction enrichment and iFISH strategies to detect and classify disseminated and circulating tumors cells. PMID- 26861906 TI - Estimating Emissions and Environmental Fate of Di-(2-ethylhexyl) Phthalate in Yangtze River Delta, China: Application of Inverse Modeling. AB - A georeferenced multimedia model was developed for evaluating the emissions and environmental fate of di-2-ethylhexyl phthalate (DEHP) in the Yangtze River Delta (YRD), China. Due to the lack of emission inventories, the emission rates were estimated using the observed concentrations in soil as inputs for the multimedia model solved analytically in an inverse manner. The estimated emission rates were then used to evaluate the environmental fate of DEHP with the regular multimedia modeling approach. The predicted concentrations in air, surface water, and sediment were all consistent with the ranges and spatial variations of observed data. The total emission rate of DEHP in YRD was 13.9 thousand t/year (95% confidence interval: 9.4-23.6), of which urban and rural sources accounted for 47% and 53%, respectively. Soil in rural areas and sediment stored 79% and 13% of the total mass, respectively. The air received 61% of the total emissions of DEHP but was only associated with 0.2% of the total mass due to fast degradation and intensive deposition. We suggest the use of an inverse modeling approach under a tiered risk assessment framework to assist future development and refinement of DEHP emission inventories. PMID- 26861905 TI - Correlation of CTNNB1 Mutation Status with Progression Arrest Rate in RECIST Progressive Desmoid-Type Fibromatosis Treated with Imatinib: Translational Research Results from a Phase 2 Study of the German Interdisciplinary Sarcoma Group (GISG-01). AB - BACKGROUND: CTNNB1 gene mutations are the molecular key events in the majority of sporadic desmoid-type fibromatosis (DF). The specific S45F mutation has been reported to be associated with a more aggressive clinical course in DF. For the current study, the CTNNB1 mutation status was analyzed in DF samples from the prospective German Interdisciplinary Sarcoma Group (GISG) phase 2 study evaluating imatinib to induce progression arrest in DF Response Evaluation Criteria In Solid Tumors (RECIST) progressive patients. METHODS: Thirty-seven patients were treated with a planned dose of imatinib 800 mg daily over 2 years (NCT01137916). The progression arrest rate (PAR) after 6 months of treatment was the primary endpoint of the study. CTNNB1 exon 3 mutation status was analyzed using Sanger sequencing. RESULTS: Thirty-three (97 %) of 34 patients reaching the primary endpoint were evaluable for CTNNB1 mutation exon 3 status. T41A mutations accounted for 30.3 % of the study samples and S45 mutations for 48.5 %, whereas CTNNB1 wild-type status was found in 21.2 %. The respective PAR at 6 months was 70, 81, and 43 %. Patients harboring CTNNB1 mutations demonstrated a higher PAR compared to wild-type DF. There was a statistically significant difference comparing patients with S45F mutations (85 % PAR) versus wild-type status (p = 0.05). CONCLUSIONS: Mutations at position S45 were overrepresented in the GISG-01 trial recruiting RECIST progressive patients only. The positive correlation of CTNNB1 mutation status with the progression arrest rate after imatinib therapy supports the idea of a potential predictive impact of the mutation status on DF treatment decision making. PMID- 26861907 TI - Intracranial venous injury, thrombosis and repair as hallmarks of mild blast traumatic brain injury in rats: Lessons from histological and immunohistochemical studies of decalcified sectioned heads and correlative microarray analysis. AB - BACKGROUND: Many previous experimental studies of blast wave effects have reported vascular and parenchymal injury in brains extracted from the skulls prior to histopathological assessment. Brain removal disrupts vasculature and structural features of the meninges that may be sources of signs and symptoms of mild traumatic brain injury, particular at lower blast overpressures (<5psi peak). NEW METHOD: Immunohistochemical and histopathological studies have been conducted in sections from decalcified, paraffin embedded, histologically sectioned whole rat heads. These sections preserve the entire cranial contents in situ, and permit evaluation of the inner ear, central nervous system and associated vasculature. The findings could also be correlated with mRNA expression patterns from whole brains subjected to similar treatment. RESULTS: Lower levels of blast wave exposure produce primarily vascular effects in rats. Messenger RNA profiles of the whole brains showed evidence of both blast intensity and time dependent effects on vascular wound healing markers. The rats exposed to 10-11psi overpressure tended to show a similar pattern of mRNA expression changes in these vascular repair and inflammatory pathways as rats exposed to approximately 5psi overpressure, but the changes were greater. The changes in mRNA expression after a 14-15psi exposure were different and suggestive of more severe injury, particularly for DNA repair, lymphocyte activation and lymphocyte migration pathways. Histopathological examination of decalcified heads revealed that even 2.5-7.9psi blast exposures produced a high prevalence of mild venous hemorrhage and thrombosis (accompanied by inflammatory markers) in the inner ear, vertebrobasilar circulation, hippocampal choroidal fissure and the veins associated with velum interpositum. COMPARISON WITH EXISTING METHOD(S): The sites of vascular injury would not have been included in specimens extracted from the skull prior to processing. CONCLUSIONS: The isolated regions of intravascular coagulation in small veins and the isolated, very small venous hemorrhages in the subarachnoid space are worthy of consideration as factors in both healing and chronic sequelae of mild blast concussion. Although small, remnants persisted in the subarachnoid space even 42 days after a single blast exposure. The high prevalence of very mild subdural and subarachnoid hemorrhage may be a target for clinical management. PMID- 26861908 TI - Nanoscopic substructures of raft-mimetic liquid-ordered membrane domains revealed by high-speed single-particle tracking. AB - Lipid rafts are membrane nanodomains that facilitate important cell functions. Despite recent advances in identifying the biological significance of rafts, nature and regulation mechanism of rafts are largely unknown due to the difficulty of resolving dynamic molecular interaction of rafts at the nanoscale. Here, we investigate organization and single-molecule dynamics of rafts by monitoring lateral diffusion of single molecules in raft-containing reconstituted membranes supported on mica substrates. Using high-speed interferometric scattering (iSCAT) optical microscopy and small gold nanoparticles as labels, motion of single lipids is recorded via single-particle tracking (SPT) with nanometer spatial precision and microsecond temporal resolution. Processes of single molecules partitioning into and escaping from the raft-mimetic liquid ordered (Lo) domains are directly visualized in a continuous manner with unprecedented clarity. Importantly, we observe subdiffusion of saturated lipids in the Lo domain in microsecond timescale, indicating the nanoscopic heterogeneous molecular arrangement of the Lo domain. Further analysis of the diffusion trajectory shows the presence of nano-subdomains of the Lo phase, as small as 10 nm, which transiently trap the lipids. Our results provide the first experimental evidence of non-uniform molecular organization of the Lo phase, giving a new view of how rafts recruit and confine molecules in cell membranes. PMID- 26861909 TI - Canonical variate regression. AB - In many fields, multi-view datasets, measuring multiple distinct but interrelated sets of characteristics on the same set of subjects, together with data on certain outcomes or phenotypes, are routinely collected. The objective in such a problem is often two-fold: both to explore the association structures of multiple sets of measurements and to develop a parsimonious model for predicting the future outcomes. We study a unified canonical variate regression framework to tackle the two problems simultaneously. The proposed criterion integrates multiple canonical correlation analysis with predictive modeling, balancing between the association strength of the canonical variates and their joint predictive power on the outcomes. Moreover, the proposed criterion seeks multiple sets of canonical variates simultaneously to enable the examination of their joint effects on the outcomes, and is able to handle multivariate and non Gaussian outcomes. An efficient algorithm based on variable splitting and Lagrangian multipliers is proposed. Simulation studies show the superior performance of the proposed approach. We demonstrate the effectiveness of the proposed approach in an [Formula: see text] intercross mice study and an alcohol dependence study. PMID- 26861910 TI - An Efficient LCM-Based Method for Tissue Specific Expression Analysis of Genes and miRNAs. AB - Laser Capture Microdissection (LCM) is a powerful tool to isolate and study gene expression pattern of desired and less accessible cells or tissues from a heterogeneous population. Existing LCM-based methods fail to obtain high quality RNA including small RNAs from small microdissected plant tissue and therefore, are not suitable for miRNA expression studies. Here, we describe an efficient and cost-effective method to obtain both high quality RNA and miRNAs from LCM-derived embryonic root apical meristematic tissue, which is difficult to access. We have significantly modified and improved the tissue fixation, processing, sectioning and RNA isolation steps and minimized the use of kits. Isolated RNA was checked for quality with bioanalyzer and used for gene expression studies. We have confirmed the presence of 19-24 nucleotide long mature miRNAs using modified stem loop RT-PCR. This modified LCM-based method is suitable for tissue specific expression analysis of both genes and small RNAs (miRNAs). PMID- 26861913 TI - [Characteristics of Hospitalizations of Homeless Persons in Seville, Spain]. AB - OBJECTIVE: The aim was to determine the characteristics of hospital admissions of homeless persons in Seville, Spain. METHODS: Observational study of 103,802 hospital admissions of 71,756 patients admitted in the Hospitals "Virgen del Rocio" and "Virgen Macarena" (Seville), in 2013 and 2014. Bivariate analysis were performed using chi2 and t-Student tests and multivariate analysis using binomial logistic regression model. RESULTS: 0.16% (n=163) of admissions were homeless persons and 99.84% (n=103,639) were not. The mean age at admission in homeless patients was 48 years and 76.5% of them were men. Hospital deaths of homeless patients occurred being 23 years younger. 92% of hospital admissions came from emergency departments and 10.0% of their discharges were against medical advice. The average length of stay was 4.8 days longer in homeless persons and the most frequent diagnoses on admission were mental (27.0%), infectious (19.6%) and respiratory diseases (18.4%). Mental disorders were present on 83.7% of homeless patients as secondary diagnose and 77.6% referred drugs consumption. CONCLUSIONS: Hospital admissions characteristics of homeless persons were particularly different. Homeless patients were hospitalized and died at a younger age than non homeless patients. The morbidity and mortality of homeless persons reflect their vulnerable health condition. PMID- 26861914 TI - Reply to Pajoumand A, Hassanian-Moghaddam H, Zamani N's Letter to the Editor Regarding Our Article 'Adverse Events Associated with Flumazenil Treatment for the Management of Suspected Benzodiazepine Intoxication - A Systematic Review with Meta-Analyses of Randomised Trials'. PMID- 26861912 TI - Associations of 6p21.3 Region with Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy. AB - Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of blindness in aging populations. This study was conducted to investigate the associations of chromosome 6p21.3 region, including CFB-SKIV2L-TNXB-FKBPL-NOTCH4 genes, with both neovascular AMD and PCV. Six single nucleotide polymorphisms (SNPs) in this region and two known AMD associated SNPs in CFH (rs800292) and HTRA1 (rs11200638) were genotyped in a Han Chinese cohort composed of 490 neovascular AMD patients, 419 PCV patients and 1316 controls. Among the SNPs, TNXB rs12153855 and FKBPL rs9391734 conferred an increased susceptibility to neovascular AMD (P = 2.8 * 10(-4) and 0.001, OR = 1.80 and 1.76, respectively), while SKIV2L exerted a protective effect on neovascular AMD (P = 2.2 * 10(-4), OR = 0.49). Rs12153855C and rs9391734A alleles could further increase the susceptibility to AMD in subjects with rs800292, rs11200638 and rs429608 risk alleles. However, only the association of SKIV2L rs429608 remained significant after adjusting for rs800292, rs11200638 and the other 5 SNPs. The protective haplotype AATGAG exhibited significant association with neovascular AMD (permutation P = 0.015, OR = 0.34). None of the SNPs in this region was associated with PCV. Association profiles of 6p21.3 region showed discrepancy between neovascular AMD and PCV, indicating possible molecular and pathological differences between these two retinal disorders. PMID- 26861911 TI - Standardizing Flow Cytometry Immunophenotyping Analysis from the Human ImmunoPhenotyping Consortium. AB - Standardization of immunophenotyping requires careful attention to reagents, sample handling, instrument setup, and data analysis, and is essential for successful cross-study and cross-center comparison of data. Experts developed five standardized, eight-color panels for identification of major immune cell subsets in peripheral blood. These were produced as pre-configured, lyophilized, reagents in 96-well plates. We present the results of a coordinated analysis of samples across nine laboratories using these panels with standardized operating procedures (SOPs). Manual gating was performed by each site and by a central site. Automated gating algorithms were developed and tested by the FlowCAP consortium. Centralized manual gating can reduce cross-center variability, and we sought to determine whether automated methods could streamline and standardize the analysis. Within-site variability was low in all experiments, but cross-site variability was lower when central analysis was performed in comparison with site specific analysis. It was also lower for clearly defined cell subsets than those based on dim markers and for rare populations. Automated gating was able to match the performance of central manual analysis for all tested panels, exhibiting little to no bias and comparable variability. Standardized staining, data collection, and automated gating can increase power, reduce variability, and streamline analysis for immunophenotyping. PMID- 26861915 TI - Enhancing future acceptance of rural placement in Tanzania through peripheral hospital rotations for medical students. AB - BACKGROUND: Mal-distribution of health care workers is a global health challenge that exacerbates health disparities, especially in resource-limited settings. Interventions to mitigate the problem have targeted qualified personnel with little focus on medical students. However, studies have demonstrated that rural rotations positively influence students to practice in rural settings upon graduation. To evaluate the influence of peripheral rotations in a resource limited setting, the Kilimanjaro Christian Medical University College introduced a 12-week clerkship rotation in peripheral hospitals for third-year medical (MD3) students in 2012. We administered an end-of-rotation survey to assess student perceptions, and attitudes toward rural practice after graduation. METHODS: Questionnaires were voluntarily and anonymously administered to MD3 students in April 2014. The questions assessed perceptions of the experience, and attitudes towards rural practice upon graduation. The perceptions were assessed using strength of consensus measures (sCns). The effect of the experience on likelihood for rural practice was assessed using Crude Odds Ratio (COR), and predictors using Adjusted Odds Ratio (AOR) with 95 % Confidence Intervals (CI) tested at a 5 % level of significance. Variation was assessed using Hosmer and Lemeshow test Chi-square. RESULTS: 111 out of 148 MD3 students participated; 62 % were male; 62 % <25 years old; and 72 % matriculated directly from secondary school. Overall, 81 % of MD3 students were satisfied with rural rotations (sCns = 83 %). The likelihood of accepting rural practice deployment after graduation was predicted by satisfaction with the peripheral hospital rotation program (AOR, 4.32; 95 % CI, 1.44-12.96; p, 0.009) and being male (AOR, 2.73; 95 % CI, 1.09-6.84; p, 0.032). Students admitted in medical school after health-related practice trended toward a higher likelihood of accepting rural practice after graduation compared to those enrolled directly from secondary school, although the difference was not significant (AOR, 4.99; 95 % CI, 0.88-28.41; p, 0.070). The Hosmer and Lemeshow test p-value was 0.686, indicating a good fit of the model. No significant differences in satisfaction between these two groups were observed, and also no significant differences between students born in rural areas compared to those born in urban areas existed. CONCLUSION: Results indicate that satisfaction with rural rotations is associated with increased likelihood of rural practice after graduation. We conclude that opportunities may exist to reduce mal-distribution of healthcare workers through interventions that target medical students. PMID- 26861917 TI - Corrigendum: A fluorescent hormone biosensor reveals the dynamics of jasmonate signalling in plants. PMID- 26861918 TI - How imperfect mixing and differential diffusion accelerate the rate of nonlinear reactions in microfluidic channels. AB - In this paper, we show experimentally that inside a microfluidic device, where the reactants are segregated, the reaction rate of an autocatalytic clock reaction is accelerated in comparison to the case where all the reactants are well mixed. We also find that, when mixing is enhanced inside the microfluidic device by introducing obstacles into the flow, the clock reaction becomes slower in comparison to the device where mixing is less efficient. Based on numerical simulations, we show that this effect can be explained by the interplay of nonlinear reaction kinetics (cubic autocatalysis) and differential diffusion, where the autocatalytic species diffuses slower than the substrate. PMID- 26861916 TI - ApoCanD: Database of human apoptotic proteins in the context of cancer. AB - In the past decade, apoptosis pathway has gained a serious consideration being a critical cellular process in determining the cancer progression. Inverse relationship between cancer progression and apoptosis rate has been well established in the literature. It causes apoptosis proteins under the investigative scanner for developing anticancer therapies, which certainly got a success in the case of few apoptosis proteins as drug targets. In the present study, we have developed a dedicated database of 82 apoptosis proteins called ApoCanD. This database comprises of crucial information of apoptosis proteins in the context of cancer. Genomic status of proteins in the form of mutation, copy number variation and expression in thousands of tumour samples and cancer cell lines are the major bricks of this database. In analysis, we have found that TP53 and MYD88 are the two most frequently mutated proteins in cancer. Availability of other information e.g. gene essentiality data, tertiary structure, sequence alignments, sequences profiles, post-translational modifications makes it even more useful for the researchers. A user-friendly web interface is provided to ameliorate the use of ApoCanD. We anticipate that, this database will facilitate the research community working in the field of apoptosis and cancer. The database can be accessed at: http://crdd.osdd.net/raghava/apocand. PMID- 26861919 TI - In prostate cancer needle biopsies, detections of PTEN loss by fluorescence in situ hybridization (FISH) and by immunohistochemistry (IHC) are concordant and show consistent association with upgrading. AB - The prognostic value of phosphatase and tensin homolog (PTEN) loss in prostate cancer has primarily been evaluated by either fluorescence in situ hybridization (FISH) or immunohistochemistry (IHC). Previously, we found that PTEN loss by IHC was associated with increased risk of upgrading from biopsy (Gleason 3 + 3) to prostatectomy (Gleason 7+). Now, using an evaluable subset of 111 patients with adjacent biopsy sections, we analyzed the association between PTEN deletion in cancer and the odds of upgrading by a highly sensitive and specific four-color FISH assay. We also compared the concordance of PTEN loss by IHC and PTEN deletion by FISH. PTEN deletion was found in 27 % (12/45) of upgraded cases compared with 11 % (7/66) of controls (P = 0.03). Cancers with PTEN deletions were more likely to be upgraded than those without deletions (adjusting for age odds ratio = 3.40, 95 % confidence interval 1.14-10.11). With respect to concordance, of 93 biopsies with PTEN protein detected by IHC, 89 (96 %) had no PTEN deletion by FISH, and of 18 biopsies without PTEN protein by IHC, 15 had homozygous or hemizygous PTEN deletion by FISH. Only 4 biopsies of the 93 (4 %) with PTEN protein intact had PTEN deletion by FISH. When the regions of uncertainty in these biopsies were systematically studied by FISH, intra-tumoral variation of PTEN deletion was found, which could account for variation in immunoreactivity. Thus, FISH provides a different approach to determining PTEN loss when IHC is uncertain. Both FISH and IHC are concordant, showing consistent positive associations between PTEN loss and upgrading. PMID- 26861920 TI - Was acupuncture developed by Han Dynasty Chinese anatomists? AB - Anatomical dissection has begun to reveal striking similarities between gross anatomical structures and the system of nomenclature used in traditional Chinese acupuncture. This paper argues that acupuncture point nomenclature is rooted in systematic anatomical investigation of cadaveric specimens, and that acupuncture points and meridians are purposefully named to reflect observable physical form. Two types of evidence are compared: observations of physical structures based on anatomical dissection, and translation and analysis of original Chinese texts. Evidence is contextualized through in-depth practical understanding of acupuncture. Points designated as [Chinese character] tian (heavenly/superior), [Chinese character] xia (below/inferior), [Chinese character] liao (bone-hole), [Chinese character] fei (flying), [Chinese character] wei (bend), and [Chinese character] xi (mountain stream/ravine) are investigated. These acupuncture point names: (a) specify position; (b) reflect function and/or form; (c) indicate homologous structures; (d) mark unusual structures; and/or (e) describe the physical appearance of a deep (dissected) structure by likening it to a homologous everyday object. Results raise intriguing possibilities for developing an understanding of acupuncture points and meridians firmly based in the material and functional anatomy of the human body. Such an understanding has the potential to open new fields of thought about functional anatomy. It also has implications for future investigations into the mechanisms of acupuncture, and gives some insights into the possible origins of this iconic area of Chinese medicine. PMID- 26861921 TI - Nonaqueous, Mini-Dose Glucagon for Treatment of Mild Hypoglycemia in Adults With Type 1 Diabetes: A Dose-Seeking Study. AB - OBJECTIVE: To evaluate mini-dose glucagon in adults with type 1 diabetes using a stable, liquid, ready-to-use preparation. RESEARCH DESIGN AND METHODS: Twelve adults with type 1 diabetes receiving treatment with insulin pumps received subcutaneous doses of 75, 150, and 300 MUg of nonaqueous glucagon. Plasma glucose, glucagon, and insulin concentrations were measured. At 180 min, subjects received insulin followed in ~60 min by a second identical dose of glucagon. RESULTS: Mean (+/-SE) fasting glucose concentrations (mg/dL) were 110 +/- 7, 110 +/- 10, and 109 +/- 9 for the 75-, 150-, and 300-MUg doses, respectively, increasing maximally at 60 min by 33, 64, and 95 mg/dL (all P < 0.001). The post insulin administration glucose concentrations were 70 +/- 2, 74 +/- 5, and 70 +/- 2 mg/dL, respectively, with maximal increases of 19, 24, and 43 mg/dL post glucagon administration (P < 0.02) at 45-60 min. CONCLUSIONS: Subcutaneous, nonaqueous, ready-to-use G-Pen Mini glucagon may provide an alternative to oral carbohydrates for the management of anticipated, impending, or mild hypoglycemia in adults with type 1 diabetes. PMID- 26861922 TI - Text Message Support for Weight Loss in Patients With Prediabetes: A Randomized Clinical Trial. AB - OBJECTIVE: Although the benefits of in-person Diabetes Prevention Program (DPP) classes for diabetes prevention have been demonstrated in trials, effectiveness in clinical practice is limited by low participation rates. This study explores whether text message support enhances weight loss in patients offered DPP classes. RESEARCH DESIGN AND METHODS: English- and Spanish-speaking patients with prediabetes (n = 163) were randomized to the control group, which only received an invitation to DPP classes as defined by the Centers for Disease Control and Prevention, or to the text message-augmented intervention group, which also received text messages adapted from the DPP curriculum for 12 months. RESULTS: Mean weight decreased 0.6 pounds (95% CI -2.7 to 1.6) in the control group and 2.6 pounds (95% CI -5.5 to 0.2) in the intervention group (P value 0.05). Three percent weight loss was achieved by 21.5% of participants in the control group (95% CI 12.5-30.6), compared with 38.5% in the intervention group (95% CI 27.7 49.3) (absolute difference 17.0%; P value 0.02). Mean glycated hemoglobin (HbA1c) increased by 0.19% or 2.1 mmol/mol (95% CI -0.1 to 0.5%) and decreased by 0.09% or 1.0 mmol/mol (95% CI -0.2 to 0.0%) in the control group and intervention participants, respectively (absolute difference 0.28%; P value 0.07). Stratification by language demonstrated a significant treatment effect in Spanish speakers but not in English speakers. CONCLUSIONS: Text message support can lead to clinically significant weight loss in patients with prediabetes. Further study assessing effect by primary language and in an operational setting is warranted. PMID- 26861923 TI - Extra-Virgin Olive Oil Reduces Glycemic Response to a High-Glycemic Index Meal in Patients With Type 1 Diabetes: A Randomized Controlled Trial. AB - OBJECTIVE: To evaluate whether fat quality, in the context of meals with high- (HGI) or low-glycemic index (LGI), influences postprandial blood glucose (PPG) response in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: According to a randomized crossover design, 13 patients with type 1 diabetes on insulin pump consumed two series (HGI or LGI) of meals with the same carbohydrate quantity while differing for amount and quality of fat: 1) low in fat ("low fat"), 2) high in saturated fat (butter), or 3) high in monounsaturated fat (extra-virgin olive oil) (EVOO). Premeal insulin doses were based on insulin-to glycemic load ratios. Continuous glucose monitoring was performed and 6-h PPG evaluated. RESULTS: PPG was significantly different between HGI and LGI meals (P = 0.005 for time * glycemic index interaction by repeated-measures analysis [RMA]), being significantly higher during the first 3 h after the HGI meals with a later tendency to an opposite pattern. In the context of HGI meals, PPG was significantly lower after EVOO than after low fat or butter (P < 0.0001 for time * meal interaction by RMA), with a marked difference in the 0- to 3-h glucose incremental area under the curve between EVOO (mean +/- SD 198 +/- 274 mmol/L * 180 min) and either low fat (416 +/- 329) or butter (398 +/- 355) (P < 0.05). No significant differences were observed in PPG between the three LGI meals. CONCLUSIONS: Carbohydrate quality of a mixed meal influences shape and extent of PPG. Besides, using EVOO in a HGI meal attenuates the early postprandial glucose response observed when this meal is consumed with either low fat or butter. Therefore, an optimal prandial insulin administration would require considering, in addition to the quantity of carbohydrates, the quality of both carbohydrate and fat. PMID- 26861924 TI - Intensive Diabetes Treatment and Cardiovascular Outcomes in Type 1 Diabetes: The DCCT/EDIC Study 30-Year Follow-up. AB - OBJECTIVE: Early initiation of intensive diabetes therapy aimed at achieving near normal glycemia reduces the early development of vascular complications in type 1 diabetes. We now assess whether intensive therapy compared with conventional therapy during the Diabetes Control and Complications Trial (DCCT) affected the incidence of cardiovascular disease over 30 years of follow-up. RESEARCH DESIGN AND METHODS: The DCCT randomly assigned 1,441 patients with type 1 diabetes to intensive versus conventional therapy for a mean of 6.5 years, after which 93% were subsequently monitored during the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Cardiovascular disease (nonfatal myocardial infarction and stroke, cardiovascular death, confirmed angina, congestive heart failure, and coronary artery revascularization) was adjudicated using standardized measures. RESULTS: During 30 years of follow-up in DCCT and EDIC, 149 cardiovascular disease events occurred in 82 former intensive treatment group subjects versus 217 events in 102 former conventional treatment group subjects. Intensive therapy reduced the incidence of any cardiovascular disease by 30% (95% CI 7, 48; P = 0.016), and the incidence of major cardiovascular events (nonfatal myocardial infarction, stroke, or cardiovascular death) by 32% (95% CI -3, 56; P = 0.07). The lower HbA1c levels during the DCCT/EDIC statistically account for all of the observed treatment effect on cardiovascular disease risk. Increased albuminuria was also independently associated with cardiovascular disease risk. CONCLUSIONS: Intensive diabetes therapy during the DCCT (6.5 years) has long-term beneficial effects on the incidence of cardiovascular disease in type 1 diabetes that persist for up to 30 years. PMID- 26861927 TI - Association of Statin Use and Reduced Risk of Lower-Extremity Amputation Among Patients With Diabetes: A Nationwide Population-Based Cohort Observation. PMID- 26861925 TI - Association of Multiple Biomarkers of Iron Metabolism and Type 2 Diabetes: The EPIC-InterAct Study. AB - OBJECTIVE: Observational studies show an association between ferritin and type 2 diabetes (T2D), suggesting a role of high iron stores in T2D development. However, ferritin is influenced by factors other than iron stores, which is less the case for other biomarkers of iron metabolism. We investigated associations of ferritin, transferrin saturation (TSAT), serum iron, and transferrin with T2D incidence to clarify the role of iron in the pathogenesis of T2D. RESEARCH DESIGN AND METHODS: The European Prospective Investigation into Cancer and Nutrition InterAct study includes 12,403 incident T2D cases and a representative subcohort of 16,154 individuals from a European cohort with 3.99 million person-years of follow-up. We studied the prospective association of ferritin, TSAT, serum iron, and transferrin with incident T2D in 11,052 cases and a random subcohort of 15,182 individuals and assessed whether these associations differed by subgroups of the population. RESULTS: Higher levels of ferritin and transferrin were associated with a higher risk of T2D (hazard ratio [HR] [95% CI] in men and women, respectively: 1.07 [1.01-1.12] and 1.12 [1.05-1.19] per 100 MUg/L higher ferritin level; 1.11 [1.00-1.24] and 1.22 [1.12-1.33] per 0.5 g/L higher transferrin level) after adjustment for age, center, BMI, physical activity, smoking status, education, hs-CRP, alanine aminotransferase, and gamma-glutamyl transferase. Elevated TSAT (>=45% vs. <45%) was associated with a lower risk of T2D in women (0.68 [0.54-0.86]) but was not statistically significantly associated in men (0.90 [0.75-1.08]). Serum iron was not associated with T2D. The association of ferritin with T2D was stronger among leaner individuals (Pinteraction < 0.01). CONCLUSIONS: The pattern of association of TSAT and transferrin with T2D suggests that the underlying relationship between iron stores and T2D is more complex than the simple link suggested by the association of ferritin with T2D. PMID- 26861926 TI - Metabolic Impact of Nonalcoholic Steatohepatitis in Obese Patients With Type 2 Diabetes. AB - OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is increasingly common in obese patients. However, its metabolic consequences in patients with type 2 diabetes mellitus (T2DM) are unknown. RESEARCH DESIGN AND METHODS: We studied 154 obese patients divided in four groups: 1) control (no T2DM or NAFLD), 2) T2DM without NAFLD, 3) T2DM with isolated steatosis, and 4) T2DM with NASH. We evaluated intrahepatic triglycerides by proton MRS ((1)H-MRS) and assessed insulin secretion/resistance during an oral glucose tolerance test and a euglycemic hyperinsulinemic clamp with glucose turnover measurements. RESULTS: No significant differences among groups were observed in sex, BMI, or total body fat. Metabolic parameters worsened progressively with the presence of T2DM and the development of hepatic steatosis, with worse hyperinsulinemia, insulin resistance, and dyslipidemia (hypertriglyceridemia and low HDL cholesterol) in those with NASH (P < 0.001). Compared with isolated steatosis, NASH was associated with more dysfunctional and insulin-resistant adipose tissue (either as insulin suppression of plasma FFA [33 +/- 3 vs. 48 +/- 6%] or adipose tissue insulin resistance index [9.8 +/- 1.0 vs. 5.9 +/- 0.8 mmol/L ? uIU/mL]; both P < 0.03). Furthermore, insulin suppression of plasma FFA correlated well with hepatic steatosis (r = -0.62; P < 0.001) and severity of steatohepatitis (rs = 0.52; P < 0.001). Hepatic insulin sensitivity was also more significantly impaired among patients with T2DM and NASH, both fasting and with increasing insulin levels within the physiological range (10 to 140 uIU/mL), compared with other groups. CONCLUSIONS: In obese patients with T2DM, the presence of NAFLD is associated with more severe hyperinsulinemia, dyslipidemia, and adipose tissue/hepatic insulin resistance compared with patients without NAFLD. The unfavorable metabolic profile linked to NAFLD should prompt strategies to identify and treat this population early on. PMID- 26861928 TI - Non-invasive insight into the release mechanisms of a poorly soluble drug from amorphous solid dispersions by confocal Raman microscopy. AB - In this study, we investigated the release mechanism of the poorly water soluble drug aprepitant from different amorphous solid dispersions using confocal Raman microscopy (CRM). Solid dispersions were fabricated based on either Soluplus(r), as an amphiphilic copolymer and solubilizer, or on polyvinylpyrrolidone, as a hydrophilic polymer, in order to elucidate the influence of the polymer characteristics on the drug form and dissolution mechanisms. Aprepitant exhibited its amorphous form in both solid dispersions. However, the release differed depending on the polymer. The high complexation effect of Soluplus was shown to be a crucial factor for stabilization of the amorphous drug, resulting in continuous release without any recrystallization of aprepitant. In contrast, solid dispersions based on polyvinylpyrrolidone showed a different mechanism of dissolution; due to the good affinity of PVP and water, the polymer is dissolving fast, leading to phase separation and local recrystallization of the drug. The study highlights the complexity of release processes from solid dispersions and elucidates the influence of the polymer on drug release kinetics. PMID- 26861930 TI - Bending response of single layer MoS2. AB - Using molecular mechanics (or dynamics) simulations, three different approaches, including the targeted molecular mechanics, four-point bending and nanotube methods, are employed to investigate the bending response of single layer MoS2 (SLMoS2), among which four-point bending is the most accurate approach to determine the bending stiffness according to the continuum theory. It is found that when the bending curvature radius is large enough (e.g. >4 nm), three approaches will give the same bending stiffness of SLMoS2 and the bending behavior is isotropic for SLMoS2, whereas the nanotube method with small tubes (e.g. <4 nm) cannot give the correct bending stiffness. Compared with the reported result from the MoS2 nanotube calculated by density functional theory, the revised Stillinger-Weber (SW) and reactive empirical bond-order (REBO) potentials can give the reasonable bending stiffness of SLMoS2 (8.7-13.4 eV) as well as the effective deformed conformation. In addition, since the Mo-S bond deformation of SLMoS2 under bending is similar to that under in-plane tension/compression, the continuum bending theory can quite accurately predict the bending stiffness of SLMoS2 if a reasonable thickness of SLMoS2 is given. For SLMoS2, the reasonable thickness should be larger than the distance between its two S atomic planes and lower than the distance between two Mo atomic planes of bulk MoS2 crystal, e.g. 0.375-0.445 nm. PMID- 26861929 TI - Enabling thermal processing of ritonavir-polyvinyl alcohol amorphous solid dispersions by KinetiSol(r) Dispersing. AB - Polyvinyl alcohol has received little attention as a matrix polymer in amorphous solid dispersions (ASDs) due to its thermal and rheological limitations in extrusion processing and limited organic solubility in spray drying applications. Additionally, in extrusion processing, the high temperatures required to process often exclude thermally labile APIs. The purpose of this study was to evaluate the feasibility of processing polyvinyl alcohol amorphous solid dispersions utilizing the model compound ritonavir with KinetiSol(r) Dispersing (KSD) technology. The effects of KSD rotor speed and ejection temperature on the physicochemical properties of the processed material were evaluated. Powder X-ray diffraction and modulated differential scanning calorimetry were used to confirm amorphous conversion. Liquid chromatography-mass spectroscopy was used to characterize and identify degradation pathways of ritonavir during KSD processing and (13)C nuclear magnetic resonance spectroscopy was used to investigate polymer stability. An optimal range of processing conditions was found that resulted in amorphous product and minimal to no drug and polymer degradation. Drug release of the ASD produced from the optimal processing conditions was evaluated using a non sink, pH-shift dissolution test. The ability to process amorphous solid dispersions with polyvinyl alcohol as a matrix polymer will enable further investigations of the polymer's performance in amorphous systems for poorly water soluble compounds. PMID- 26861931 TI - Material Hardship and Internal Locus of Control Over the Prevention of Child Obesity in Low-Income Hispanic Pregnant Women. AB - OBJECTIVE: To determine the relations between household material hardships and having a low internal locus of control over the prevention of child obesity in low-income Hispanic pregnant women. METHODS: We performed a cross-sectional analysis of baseline data collected during a third trimester prenatal visit from women participating in the Starting Early Study, a randomized controlled trial to test the efficacy of a primary care-based family-centered early child obesity prevention intervention. Using multiple logistic regression analyses, we determined whether 4 domains of material hardship (food insecurity, difficulty paying bills, housing disrepair, neighborhood stress), considered individually and also cumulatively, were associated with having a low internal locus of control over the prevention of child obesity. RESULTS: The sample included 559 low-income Hispanic pregnant women, with 60% having experienced at least 1 hardship. Food insecurity was independently associated with a low internal locus of control over the prevention of child obesity (adjusted odds ratio, 2.38; 95% confidence interval, 1.50-3.77), controlling for other hardships and confounders. Experiencing a greater number of material hardships was associated in a dose dependent relationship with an increased odds of having a low internal locus of control. CONCLUSIONS: Prenatal material hardships, in particular food insecurity, were associated with having a lower prenatal internal locus of control over the prevention of child obesity. Longitudinal follow-up of this cohort is needed to determine how relations between material hardships and having a low internal locus of control will ultimately affect infant feeding practices and child weight trajectories. PMID- 26861932 TI - Bypassing Primary Care Facilities for Childbirth: Findings from a Multilevel Analysis of Skilled Birth Attendance Determinants in Afghanistan. AB - INTRODUCTION: The objective of this study was to assess the association between health facility characteristics and other individual/household factors with a woman's likelihood of skilled birth attendance in north-central Afghanistan. METHODS: Data from a 2010 household survey of 6879 households in 9 provinces of Afghanistan were linked to routine facility data. Hierarchical logistic regression models were used to assess determinants of skilled birth attendance. RESULTS: Women who reported having at least one antenatal visit with a skilled provider were 5.6 times more likely to give birth with a skilled attendant than those who did not. The odds of skilled birth attendance were 84% higher for literate women than those without literacy skills and 79% higher among women in the upper 2 wealth quintiles than women in the poorest quintile. This study did not show any direct linkages between facility characteristics and skilled birth attendance but provided insights into why studies assuming that women seek care at the nearest primary care facility may lead to misinterpretation of care seeking patterns. Findings reveal a 36 percentage point gap between women who receive skilled antenatal care and those who received skilled birth care. Nearly 60% of women with a skilled attendant at their most recent birth bypassed the nearest primary care facility to give birth at a more distant primary care facility, hospital, or private clinic. Distance and transport barriers were reported as the most common reasons for home birth. DISCUSSION: Assumptions that women who give birth with a skilled attendant do so at the closest health facility may mask the importance of supply-side determinants of skilled birth attendance. More research based on actual utilization patterns, not assumed catchment areas, is needed to truly understand the factors influencing care seeking decisions in both emergency and nonemergency situations and to adapt strategies to reduce preventable mortality and morbidity in Afghanistan. PMID- 26861935 TI - Immigrant mothers and access to prenatal care: evidence from a regional population study in Italy. AB - OBJECTIVES: We addressed the question of whether use of adequate prenatal care differs between foreign-born and Italian mothers and estimated the extent to which unobservable characteristics bias results. SETTING: This study is on primary care and especially on adequate access to prenatal healthcare services by immigrant mothers. PARTICIPANTS: Approximately 37,000 mothers of both Italian and foreign nationality were studied. Data were obtained from the Standard Certificate of Live Birth between 2005 and 2010 in Umbria. RESULTS: Estimates from the bivariate probit model indicate that immigrant mothers are three times more likely to make fewer than four prenatal visits (OR=3.35) and 1.66 times more likely to make a late first visit (OR=1.66). The effect is found to be strongest for Asian women. CONCLUSIONS: Standard probit models lead to underestimation of the probability of inadequate use of prenatal care services by immigrant women, whereas bivariate probit models, which allow us to consider immigrant status as an endogenous variable, estimated ORs to be three times larger than those obtained with univariate models. PMID- 26861933 TI - Adiposity and response to an obesity prevention intervention in Pakistani and Bangladeshi primary school boys and girls: a secondary analysis using the BEACHeS feasibility study. AB - OBJECTIVES: As a secondary analysis of the BEACHeS study, we hypothesised there would be sex differences in Pakistani and Bangladeshi school children when examining adiposity and their response to an obesity intervention. DESIGN: The Birmingham healthy Eating and Active lifestyle for CHildren Study (BEACHeS) was designed as a Phase II feasibility study of a complex intervention. SETTING: 8 primary schools with predominantly South Asian children in Birmingham, UK PARTICIPANTS: 1090 pupils (aged 5-7 years old) from school year 1 and 2 were allocated at school level to receive an intervention. A total of 574 were enrolled in the study with consent. We focused on the 466 children of Pakistani and Bangladeshi origin (50.6% boys). INTERVENTION: Delivered between 2007 and 2009, the 1-year obesity prevention intervention targeted school and family-based dietary and physical activities. PRIMARY AND SECONDARY OUTCOME MEASURES AND ANALYSIS: Adiposity measures including skinfold thickness were compared by sex at baseline and follow-up. Gains in adiposity measures were compared between control and intervention arms in boys and in girls. Measures were compared using two sample t tests and Wilcoxon-Mann-Whitney rank sum tests according to normality distribution. RESULTS: At baseline, girls had larger skinfold measures at all sites compared to boys although body mass index (BMI) was similar (eg, median subscapular skinfold 6.6 mm vs 5.7 mm; p<0.001). At follow-up, girls in the intervention group gained less weight and adiposity compared to respective controls (p<0.05 for weight, BMI, waist circumference, central and thigh skinfold) with a median total skinfold gain of 7.0 mm in the control group compared to 0.3 mm in the intervention group. CONCLUSIONS: Our secondary analysis suggests differences in adiposity in Pakistani and Bangladeshi girls and boys and in the effect of the intervention reducing adiposity in girls. These preliminary findings indicate that including sex differences should be examined in future trials. TRIAL REGISTRATION NUMBER: ISRCTN51016370; Post-results. PMID- 26861934 TI - Registered nurse, healthcare support worker, medical staffing levels and mortality in English hospital trusts: a cross-sectional study. AB - OBJECTIVES: To examine associations between mortality and registered nurse (RN) staffing in English hospital trusts taking account of medical and healthcare support worker (HCSW) staffing. SETTING: Secondary care provided in acute hospital National Health Service (NHS) trusts in England. PARTICIPANTS: Two data sets are examined: Administrative data from 137 NHS acute hospital trusts (staffing measured as beds per staff member). A cross-sectional survey of 2917 registered nurses in a subsample of 31 trusts (measured patients per ward nurse). OUTCOME MEASURE: Risk-adjusted mortality rates for adult patients (administrative data). RESULTS: For medical admissions, higher mortality was associated with more occupied beds per RN (RR 1.22, 95% CI 1.04 to 1.43, p=0.02) and per doctor (RR 1.10, 95% CI 1.05 to 1.15, p <0.01) employed by the trust whereas, lower HCSW staffing was associated with lower mortality (RR 0.95, 95% CI 0.91 to 1.00, p=0.04). In multivariable models the relationship was statistically significant for doctors (RR 1.08, 95% CI 1.02 to 1.15, p=0.02) and HCSWs (RR 0.93, 95% CI 0.89 to 0.98, p<01) but not RNs (RR 1.14, 95% CI 0.95 to 1.38, p=0.17). Trusts with an average of <= 6 patients per RN in medical wards had a 20% lower mortality rate compared to trusts with >10 patients per nurse (RR 0.80, 95% CI 0.76 to 0.85, p<0.01). The relationship remained significant in the multivariable model (RR 0.89, 95% CI 0.83 to 0.95, p<0.01). Results for surgical wards/admissions followed a similar pattern but with fewer significant results. CONCLUSIONS: Ward-based RN staffing is significantly associated with reduced mortality for medical patients. There is little evidence for beneficial associations with HCSW staffing. Higher doctor staffing levels is associated with reduced mortality. The estimated association between RN staffing and mortality changes when medical and HCSW staffing is considered and depending on whether ward or trust wide staffing levels are considered. PMID- 26861936 TI - Exploring provision of Innovative Community Education Placements (ICEPs) for junior doctors in training: a qualitative study. AB - OBJECTIVE: Medical education in community settings is an essential ingredient of doctors' training and a key factor in recruiting general practitioners (GP). Health Education England's report 'Broadening the Foundation' recommends foundation doctors complete 4-month community placements. While Foundation GP schemes exist; other community settings, are not yet used for postgraduate training. The objective of this study was to explore how community-based training of junior doctors might be expanded into possible 'innovative community education placements' (ICEPs), examining opportunities and barriers to these developments. DESIGN: A qualitative study where semistructured interviews were undertaken and themes were generated deductively from the research questions, and iteratively from transcripts. SETTING: UK community healthcare. PARTICIPANTS: Stakeholders from UK Community healthcare providers and undergraduate GP and community educators. RESULTS: Nine participants were interviewed; those experienced in delivering community-based undergraduate education, and others working in community settings that had not previously trained doctors. Themes identified were practicalities such as 'finance and governance', 'communication and interaction', 'delivery of training' and 'perceptions of community'. ICEPs were willing to train Foundation doctors. However, concerns were raised that large numbers and inadequate resources could undermine the quality of educational opportunities, and even cause reputational damage. Organisation was seen as a challenge, which might be best met by placing some responsibility with trainees to manage their placements. ICEP providers agreed that defined service contribution by trainees was required to make placements sustainable, and enhance learning. ICEPs stated the need for positive articulation of the learning value of placements to learners and stakeholders. CONCLUSIONS: This study highlighted the opportunities for foundation doctors to gain specialist and generalist knowledge in ICEPs from diverse clinical teams and patients. We recommend in conclusion ways of dealing with some of the perceived barriers to training. PMID- 26861937 TI - Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case-control study. AB - OBJECTIVES: To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. DESIGN: Case control study. SETTING: An Iranian referral university hospital. PARTICIPANTS: 176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two dimensional and M-mode echocardiography. The I/D polymorphism of the ACE gene was determined using the PCR method. RESULTS: The D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models. CONCLUSIONS: In patients with hypertension who develop HFpEF, the D allele of the ACE gene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart's diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease. PMID- 26861938 TI - Utilisation of helicopter emergency medical services in the early medical response to major incidents: a systematic literature review. AB - OBJECTIVE: This systematic review identifies, describes and appraises the literature describing the utilisation of helicopter emergency medical services (HEMS) in the early medical response to major incidents. SETTING: Early prehospital phase of a major incident. DESIGN: Systematic literature review performed according to Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Web of Science, PsycINFO, Scopus, Cinahl, Bibsys Ask, Norart, Svemed and UpToDate were searched using phrases that combined HEMS and 'major incidents' to identify when and how HEMS was utilised. The identified studies were subjected to data extraction and appraisal. RESULTS: The database search identified 4948 articles. Based on the title and abstract, the full text of 96 articles was obtained; of these, 37 articles were included in the review, and an additional five were identified by searching the reference lists of the 37 articles. HEMS was used to transport medical and rescue personnel to the incident and to transport patients to the hospital, especially when the infrastructure was damaged. Insufficient air traffic control, weather conditions, inadequate landing sites and failing communication were described as challenging in some incidents. CONCLUSIONS: HEMS was used mainly for patient treatment and to transport patients, personnel and equipment in the early medical management of major incidents, but the optimal utilisation of this specialised resource remains unclear. This review identified operational areas with improvement potential. A lack of systematic indexing, heterogeneous data reporting and weak methodological design, complicated the identification and comparison of incidents, and more systematic reporting is needed. TRIAL REGISTRATION NUMBER: CRD42013004473. PMID- 26861939 TI - Methods of a large prospective, randomised, open-label, blinded end-point study comparing morning versus evening dosing in hypertensive patients: the Treatment In Morning versus Evening (TIME) study. AB - INTRODUCTION: Nocturnal blood pressure (BP) appears to be a better predictor of cardiovascular outcome than daytime BP. The BP lowering effects of most antihypertensive therapies are often greater in the first 12 h compared to the next 12 h. The Treatment In Morning versus Evening (TIME) study aims to establish whether evening dosing is more cardioprotective than morning dosing. METHODS AND ANALYSIS: The TIME study uses the prospective, randomised, open-label, blinded end-point (PROBE) design. TIME recruits participants by advertising in the community, from primary and secondary care, and from databases of consented patients in the UK. Participants must be aged over 18 years, prescribed at least one antihypertensive drug taken once a day, and have a valid email address. After the participants have self-enrolled and consented on the secure TIME website (http://www.timestudy.co.uk) they are randomised to take their antihypertensive medication in the morning or the evening. Participant follow-ups are conducted after 1 month and then every 3 months by automated email. The trial is expected to run for 5 years, randomising 10,269 participants, with average participant follow-up being 4 years. The primary end point is hospitalisation for the composite end point of non-fatal myocardial infarction (MI), non-fatal stroke (cerebrovascular accident; CVA) or any vascular death determined by record linkage. Secondary end points are: each component of the primary end point, hospitalisation for non-fatal stroke, hospitalisation for non-fatal MI, cardiovascular death, all-cause mortality, hospitalisation or death from congestive heart failure. The primary outcome will be a comparison of time to first event comparing morning versus evening dosing using an intention-to-treat analysis. The sample size is calculated for a two-sided test to detect 20% superiority at 80% power. ETHICS AND DISSEMINATION: TIME has ethical approval in the UK, and results will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: UKCRN17071; Pre-results. PMID- 26861941 TI - Altered inhibitory interaction among inferior frontal and motor cortex in l-dopa induced dyskinesias. AB - BACKGROUND: Levodopa-induced dyskinesias are associated with thalamo-cortical disinhibition and frontal area overactivation. Neuroimaging and transcranial magnetic stimulation studies have highlighted the involvement of the right inferior frontal cortex in levodopa-induced dyskinesias. METHODS: Using transcranial magnetic stimulation, we tested connectivity between the inferior frontal and contralateral motor cortex in Parkinson's disease patients with and without levodopa-induced dyskinesias compared with age-matched controls. Furthermore, in dyskinetic patients, connectivity between the inferior frontal and contralateral motor cortex was assessed before and after a single session of continuous theta-burst stimulation applied over the inferior frontal cortex. RESULTS: Dyskinetic patients showed abnormal facilitatory connectivity between the inferior frontal and motor cortex when compared with the nondyskinetic group. Continuous theta-burst stimulation over the inferior frontal cortex eliminated such facilitatory connectivity and decreased the levodopa-induced dyskinesias that was induced by a supramaximal dose of levodopa. CONCLUSION: In dyskinetic patients, a weaker inhibitory cortico-cortical interaction between the inferior frontal and contralateral motor cortex could be involved in levodopa-induced dyskinesias and restored by continuous theta-burst stimulation over the inferior frontal cortex. (c) 2016 Movement Disorder Society. PMID- 26861940 TI - Identification of Lactobacillus proteins with different recognition patterns between immune rabbit sera and nonimmune mice or human sera. AB - BACKGROUND: The genus Lactobacillus belongs to a large heterogeneous group of low G + C Gram-positive anaerobic bacteria, which are frequently used as probiotics. The health-beneficial effects, in particular the immunomodulation effect, of probiotics depend on the strain and dose used. Strain variations may be related to diversity of the cell surface architecture of bacteria and the ability to express specific antigens or secrete compounds. The use of Lactobacillus as probiotic requires a comprehensive understanding of its effect on host immune system. To evaluate the potential immunoreactive properties of proteins isolated from four Lactobacillus strains: L. johnsonii 142 and L. johnsonii 151, L. rhamnosus LOCK 0900 and L. casei LOCK 0919, the polyclonal sera obtained from mouse and human have been tested as well as with sera from rabbits immunized with whole lactobacilli cells. RESULTS: The reactivity of isolated proteins detected by SDS-PAGE and Western blotting was heterogeneous and varied between different serum samples. The proteins with the highest immunoreactivity were isolated, purified and sequenced, in particular the fractions were identified as phosphoglycerate kinase (L. johnsonii 142), glyceraldehyde 3-phosphate dehydrogenase (L. johnosnii 142, L. rhamnosus LOCK 0900), hypothetic protein JDM1_1307 (L. johnsonii 151) and fructose/tagatose-bisphosphate-aldolase (L. casei LOCK 0919). CONCLUSION: The different prevalence of reactions against tested antigens in rabbit, mouse and human sera may indicate significant differences in immune system and commensal cross-talk in these groups. The identification of immunoreactive lactobacilli proteins opens the possibility to use them as an antigens for development of vaccines. PMID- 26861942 TI - Dental practitioner recruitment for a randomized clinical trial in the field to evaluate the performance of a new glass ionomer restoration material. AB - BACKGROUND: In 2009, we began recruiting dental practitioners across Germany to participate in a clinical trial to evaluate the clinical performance of EQUIA, a new glass ionomer restoration material. The aim of this paper is to discuss the outcomes of the dental practitioner recruitment and outline the process of establishing a practice-based research network. METHODS: Study proposals were sent to randomly selected dental offices in 29 cities in Germany. The proposals were sent until a minimum of 10 clinics in each city declared participation. Later on, briefing lectures informed the participating practitioners about the design, methods, and material application procedure. Participants were familiarized with the guidelines of Good Manufacturing Practice (GMP) and Good Epidemiological Practice (GEP). A questionnaire describing the characteristics of each dental office was filled out by the participating practitioner. Additionally, participation levels were characterized according to the socioeconomic status and geographic districts of residence in Germany (Regions 0 to 9). The associations between the characteristics were tested by the Kruskal Wallis Test and Chi-squared test (P < 0.05). RESULTS: A total of 3194 private dental clinics were invited, 1712 clinics refused to participate, 1195 did not respond to the invitation, and 323 agreed to participate. Only 144 clinics participated in the lectures held in their cities and signed the participation agreement. Based on their geographic location, the highest participation was in Region 2 with a participation rate of 14.3%, and the lowest participation was in Region 6 with a participation rate of 1.7%. Regions with the lowest rate of unemployment and relatively higher rates of income (Regions 7 and 8) had the highest rate of refusals (86%). CONCLUSION: The initial results of the dental practitioner recruitment in this study suggest that the recruitment and pre randomization design were successful, and by reaching out to a considerable number of private dental clinics to participate, we were able to recruit a smaller number of highly motivated dentists in this clinical study. Regional differences in socioeconomic status, practitioner specialization, and differences in patient health care insurance have to be considered when recruiting dental practitioners for clinical trials. TRIAL REGISTRATION: The trial has been registered at Deutsches Register Klinischer Studien (German register of clinical trials) on 6 September 2012 under DRKS-ID: DRKS00004220. PMID- 26861943 TI - Longitudinal household surveillance for malaria in Rakai, Uganda. AB - BACKGROUND: HIV and malaria exert co-pathogenic effects. Malaria surveillance data are necessary for public health strategies to reduce the burden of disease in high HIV prevalence settings. METHODS: This was a longitudinal cohort study to assess the burden of malaria in rural Rakai, Uganda. Households were visited monthly for 1 year to identify confirmed clinical malaria (CCM), or parasitaemia with temperature >37.5 degrees C, and asymptomatic parasitaemia (AP). Interviews of the adult or child's caregiver and clinical and laboratory assessments were conducted. Rapid diagnostic testing for malaria and anaemia was performed if participants were febrile and anti-malarial treatment given per Uganda Ministry of Health 2010 guidelines. Blood was drawn at every household visit to assess for parasitaemia, and blood smears were assessed at the Rakai Health Science Programme laboratory. RESULTS: A total of 1640 participants were enrolled, including 975 children aged 6 months up to 10 years, 393 adult caregivers, and 272 adolescent/adult household members from 393 randomly selected households in two representative communities. 1459 (89 %) participants completed all study visits. CCM was identified in 304 (19 %) participants, with the highest incidence rate for CCM of 0.38 per person-year (ppy) identified in children <5 years, and rates decreased with age; the rates were 0.27, 0.16, and 0.09 ppy for ages 5-<10 years, 10-<18 years, and adults 18+ years, respectively. AP was identified in 943 (57 %) participants; the incidence rate was 1.99 ppy for <5 years, 2.72 ppy for 5 <10 years, 2.55 ppy for 10-<18 years, and 0.86 ppy among adults, with 92 % of cases being attributed to Plasmodium falciparum by smear. 994 (61 %) individuals had at least one positive smear; 342 (21 %) had one positive result, 203 (12 %) had two, 115 (7 %) had three, and 334 (21 %) had >3 positive smears during follow up. Seasonal rates generally followed the rains and peaked during July, then decreased through November before increasing again. CONCLUSIONS: Plasmodium falciparum infection remains high in rural Uganda. Increased malaria control interventions should be prioritized. Trial registration Clinicaltrials.gov identifier NCT01265407. PMID- 26861944 TI - Symptoms of periodontitis and antibody responses to Porphyromonas gingivalis in juvenile idiopathic arthritis. AB - BACKGROUND: The association between rheumatoid arthritis (RA) and periodontitis is well established. Some children with juvenile idiopathic arthritis (JIA) phenotypically resemble adults with RA, characterized by the presence of anti cyclic citrullinated peptide (CCP) antibodies. We sought to investigate an association between CCP-positive JIA and symptoms of periodontitis and antibodies to oral microbiota. METHODS: Antibodies to oral pathogens Porphyromonas gingivalis, Prevotella intermedia, and Fusobacterium nucleatum were measured using ELISA in 71 children with CCP-positive JIA and 74 children with CCP negative JIA. Oral health history was collected from 37 children with CCP positive JIA and 121 children with CCP-negative JIA. T-tests, Chi-square tests, Mann-Whitney U tests, and multivariable regression were used to compare the groups. RESULTS: Compared to those with CCP-negative JIA, children with CCP positive JIA were more likely to be female, older and non-Caucasian. Anti-P. gingivalis (p <0.003) and anti-P. intermedia (p <0.008) IgG antibody titers were higher in the CCP-positive cohort. Differences in P. gingivalis antibody titers remained significant after adjusting for age (p = 0.007). Children with CCP positive JIA more likely reported tender/bleeding gums (43 % vs. 24 %, p < 0.02) compared to children with CCP-negative JIA. After controlling for age at collection, the odds of having tender/bleeding gums were 2.2 times higher in the CCP-positive group compared (95 % CI 0.98 - 4.83; p = 0.056). CONCLUSIONS: Children with CCP-positive JIA have higher antibody titers to P. gingivalis and more symptoms of poor oral health, supporting a possible role for periodontitis in the etiology of CCP-positive JIA. PMID- 26861946 TI - Associations between lower urinary tract dysfunction and glycemic control in women with type 2 diabetes: A cross-sectional study. AB - AIMS: Patients with diabetes are predisposed to develop a variety of complications, including lower urinary tract (LUT) dysfunction. We aimed to examine the associations between glycemic control and LUT dysfunction in women with type 2 diabetes (T2D). METHODS: We included 400 women with T2D (age range, 48-75 years) in this cross-sectional analysis. The participants were divided into tertiles according to glycosylated hemoglobin (HbA1c) measurements. The mean HbA1c levels for tertiles 1, 2, and 3 were 6.2% (N=132), 7.1% (N=132), and 8.4% (N=136), respectively. We evaluated LUT dysfunction with the American Urological Association Symptom Index (AUA-SI) questionnaire, uroflowmetry (UFM), and post void residual (PVR). RESULTS: No significant differences were found among HbA1c tertiles regarding storage, voiding and total AUA-SI scores, and prevalence of LUT symptoms. However, women in tertile 3 had higher prevalences of severe LUT symptoms (AUA-SI>=20) and clinically significant PVR (>=100mL) compared to women in the other tertiles. Multivariate analysis revealed that diabetic neuropathy, but not HbA1c, significantly predicted LUT symptoms in women with T2D after adjustment for age, body mass index (BMI) and hypertension. However, HbA1c was associated with an increased risk of developing clinically significant PVR. CONCLUSIONS: Our findings do not support significant associations between glycemic control and LUT symptoms in women with T2D. However, women with poor glycemic control are more likely to develop urinary retention than women with proper glycemic control. Clinicians should, therefore, be aware of and educate patients about the association between urinary retention and glycemic control. PMID- 26861945 TI - Late-onset spinal form xanthomatosis without brain lesion: a case report. AB - BACKGROUND: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive sterol storage disease caused by a mutated sterol 27-hydroxylase (CYP27A1) gene. Patients with typical CTX show neurological dysfunction including bilateral cataracts, paresis, cerebral ataxia, dementia, and psychiatric disorders, and magnetic resonance imaging (MRI) has revealed symmetrical lesions in the cerebellar white matter. CASE PRESENTATION: We report the case of a patient with late-onset spinal form CTX without brain lesion. He showed pyramidal tract signs, and impaired joint position and vibration sensation in the lower limbs. Cervical sagittal MRI demonstrated a longitudinally extensive white matter abnormality in the dorsal column of the C2-C7 spinal cord; however, a brain MRI revealed an absence of lesions, including in the cerebellar white matter. Genetic analysis of CYP27A1 revealed that the patient was compound heterozygous for p.Gln85Arg in exon 1, a novel mutation, and p.Arg405Gln in exon 7, a previously reported mutation. CONCLUSION: This is the first report of late-onset spinal form CTX without typical neurological symptoms, and the first report of p.Gln85Arg in CYP27A1. We speculate that spinal form CTX without brain lesion is a clinically and radiologically rare variation of CTX. Therefore, spinal xanthomatosis should be included in the differential diagnosis of chronic myelopathy even with late onset and/or no other typical neurological findings. PMID- 26861947 TI - Androgen-deprivation therapy and pancreatic beta-cell dysfunction in men. PMID- 26861949 TI - Advanced oxidation protein products induce endothelial-to-mesenchymal transition in human renal glomerular endothelial cells through induction of endoplasmic reticulum stress. AB - Endothelial-to-mesenchymal transition (EndMT) in renal glomerular endothelial cells plays a critical role in the pathogenesis of diabetic nephropathy (DN). Furthermore, advanced oxidation protein products (AOPPs) have been shown to contribute to the progression of DN. However, whether AOPPs induce EndMT in renal glomerular endothelial cells remains unclear. Thus, we investigated the effect of AOPPs on human renal glomerular endothelial cells (HRGECs) and the mechanisms underlying the effects. Our results showed that AOPP treatment lowered the expression of vascular endothelial cadherin, CD31, and claudin 5 and induced the overexpression of alpha-smooth muscle actin, vimentin, and fibroblast-specific protein 1, which indicated that AOPPs induced EndMT in HRGECs. Furthermore, AOPP stimulation increased the expression of glucose-regulated protein 78 and CCAAT/enhancer-binding protein-homologous protein, which suggested that AOPPs triggered endoplasmic reticulum (ER) stress in HRGECs. Notably, the aforementioned AOPP effects were reversed following the treatment of cells with salubrinal, an inhibitor of ER stress, whereas the effects were reproduced after exposure to thapsigargin, an inducer of ER stress. Collectively, our results indicate that AOPPs trigger EndMT in HRGECs through the induction of ER stress. These findings suggest novel therapeutic strategies for inhibiting renal fibrosis by targeting ER stress. PMID- 26861948 TI - High levels of AGE-LDL, and of IgG antibodies reacting with MDA-lysine epitopes expressed by oxLDL and MDA-LDL in circulating immune complexes predict macroalbuminuria in patients with type 2 diabetes. AB - BACKGROUND: Circulating immune complexes (IC) containing modified forms of LDL (mLDL) are strongly pro-inflammatory and when present in high levels are associated with the development of diabetic complications. OBJECTIVE: We investigated whether levels of oxidized LDL (oxLDL), malondialdehyde-LDL (MDA LDL) and advanced glycation end products-LDL (AGE-LDL) as well as IgG and IgM antibodies reacting with MDA-lysine epitopes expressed by oxLDL and MDA-LDL isolated from circulating IC were associated with progression to macroalbuminuria in type 2 diabetes (VADT cohort). METHODS: Levels of mLDL in IC were measured in 905 patients, a median of two years after entry into the study. Participants were followed for an average of 3.7years for renal outcomes. Generalized logistic regression models were used to quantify the association of increased levels of biomarkers and development of abnormal albuminuria. Normal, persistent micro- (ACR >=30), incident micro- (ACR >=30) and incident macroalbuminuria (ACR >=300) were the outcomes of interest. RESULTS AND CONCLUSIONS: Patients with macro (n=78) or non-persistent microalbuminuria (n=81) at baseline were excluded. Odds ratios for endpoints in relation to high versus low (defined using a median split) biomarker levels are found in Fig. 1. Our study demonstrates that high levels of AGE-LDL as well as of IgG antibodies (but not IgM antibodies) reacting with MDA-LDL lysine epitopes in circulating IC predict the development of macroalbuminuria in patients with type 2 diabetes. These data support the pathogenic role of modified LDL IgG antibodies but not the protective role of modified LDL IgM antibodies. PMID- 26861950 TI - Antibiofilm efficacy of honey and bee-derived defensin-1 on multispecies wound biofilm. AB - Many clinically relevant biofilms are polymicrobial. Examining the effect of antimicrobials in a multispecies biofilm consortium is of great clinical importance. The goal of this study was to investigate the effect of different honey types against bacterial wound pathogens grown in multispecies biofilm and to test the antibiofilm activity of honey defensin-1 (Def-1) in its recombinant form. A modified Lubbock chronic wound biofilm formed by four bacterial species (Staphylococcus aureus, Streptococcus agalactiae, Pseudomonas aeruginosa and Enterococcus faecalis) was used for evaluation of honey and recombinant bee derived Def-1 antibiofilm efficacy. Recombinant Def-1 was prepared by heterologous expression in Escherichia coli. We showed that different types of honey (manuka and honeydew) were able to significantly reduce the cell viability of wound pathogens (Staphylococcus aureus, Streptococcus agalactiae and Pseudomonas aeruginosa) in mature polymicrobial biofilm. None of the tested honeys showed the ability to eradicate Enterococcus faecalis in biofilm. In addition, recombinant Def-1 successfully reduced the viability of Staphylococcus aureus and Pseudomonas aeruginosa cells within established polymicrobial biofilm after 24 and 48 h of treatment. Interestingly, recombinant Def-1 did not affect the viability of Streptococcus agalactiae cells within the biofilm, whereas both natural honeys significantly reduced the viable bacteria. Although Enterococcus faecalis was highly resistant to Def-1, Def-1 significantly affected the biofilm formation of Enterococcus faecalis and Streptococcus agalactiae after 24 h of treatment, most likely by inhibiting its extracellular polymeric substances production. In conclusion, our study revealed that honey and Def-1 are effective against established multispecies biofilm; however, Enterococcus faecalis grown in multispecies biofilm was resistant to both antimicrobials. PMID- 26861951 TI - Gene expression alterations in inflamed and unaffected colon mucosa from patients with mild inflammatory bowel disease. AB - An endoscopic examination is currently the most reliable method for monitoring disease activity in patients with inflammatory bowel disease (IBD). However, endoscopic evaluations are unable to detect mucosal inflammation at the earliest stages. The present study aimed to evaluate the molecular profiles of inflamed and unaffected colon mucosa from patients with mild Crohn's disease (CD) and ulcerative colitis (UC), in order to identify a more sensitive method for monitoring mucosal impairment. Patients were recruited and colon biopsies from the inflamed and the normal-appearing mucosa of patients with mild IBD were obtained by colonoscopy. Gene expression analysis was performed using microarrays, after which Gene Ontology and clustering were performed using bioinformatics. In addition, the levels of inflammatory cytokines were analyzed by reverse transcription-quantitative polymerase chain reaction. A total of 620 genes in the inflamed and 210 genes in the unaffected colon mucosa with at least a 3-fold change, as compared with healthy controls, were detected in patients with mild CD, and 339 genes in the inflamed and 483 genes in the unaffected colon mucosa were detected in patients with mild UC. Heat mapping demonstrated a similarity in the gene alteration patterns, and altered transcripts overlapped, between the inflamed and unaffected colon mucosa. Interferon-gamma and interleukin-17 mRNA levels were comparably elevated in the inflamed and unaffected colon mucosa from patients with IBD. Marked gene expression alterations were detected in the inflamed and unaffected colon mucosa from patients with mild IBD, and these showed marked similarity and overlap between the two groups. The results of the present study suggested that inflammation was not limited to the endoscopic lesions and that gene expression profiling may be considered a sensitive tool for monitoring mucosal inflammation, predicting relapses and optimizing therapeutic strategies for patients with IBD. PMID- 26861953 TI - Pharmacotherapy of ADHD in Slovenia: realities and perspectives. PMID- 26861952 TI - Early development in children that are later diagnosed with disorders of attention and activity: a longitudinal study in the Danish National Birth Cohort. AB - Not much is known about the early development in children that are later diagnosed with disorders of attention and activity (ADHD). Using prospective information collected from mothers in the Danish National Birth Cohort (DNBC), we investigated if developmental deviations in the first years of life are associated with later ADHD. In the DNBC 76,286 mothers were interviewed about their child's development and behaviour at age 6 and 18 months. At the end of follow-up, when the children were 8-14 years of age, 2034 were registered in Danish health registers with a clinical diagnosis of ADHD. The Hazard Ratio of ADHD was estimated using Cox regression model. At 6 months of age deviations in development showed associations with the child later being diagnosed with ADHD such as duration of breastfeeding, motor functioning, and incessant crying. At 18 months, many observations clearly associated with ADHD as for example the child not being able to fetch things on request [HR 3.0 (95 % CI 2.4; 3.7)], or the child being significantly more active than average [HR 2.0 (95 % CI 1.8; 2.2)]. An association to ADHD was shown, especially at 18 months, if the mother found it difficult to handle the child [HR 2.9 (95 % CI 2.4-3.5)]. However, it goes for all observations that the positive predictive values were low. Many children with ADHD showed signs of developmental deviations during the first years of their life. In general, however, ADHD cannot be identified solely on basis of the questions in DNBC. PMID- 26861954 TI - N-Acetylcysteine and Ceftriaxone as Preconditioning Strategies in Focal Brain Ischemia: Influence on Glutamate Transporters Expression. AB - Glutamate (Glu) plays a key role in excitotoxicity-related injury in cerebral ischemia. In the brain, Glu homeostasis depends on Glu transporters, including the excitatory amino acid transporters and the cysteine/Glu antiporter (xc-). We hypothesized that drugs acting on Glu transporters, such as ceftriaxone (CEF, 200 mg/kg, i.p.) and N-acetylcysteine (NAC, 150 mg/kg, i.p.), administered repeatedly for 5 days before focal cerebral ischemia in rats and induced by a 90-min middle cerebral artery occlusion (MCAO), may induce brain tolerance to ischemia. We compared the effects of these drugs on brain infarct volume, neurological deficits and the mRNA and protein expression of the Glu transporter-1 (GLT-1) and xc- with the effects of ischemic preconditioning and chemical preconditioning using 3-nitropropionic acid. Administration of CEF and NAC significantly reduced infarct size and neurological deficits caused by a 90-min MCAO. These beneficial effects were accompanied by changes in GLT-1 expression caused by a 90-min MCAO at both the mRNA and protein levels in the frontal cortex, hippocampus, and dorsal striatum. Thus, the results of this study suggest that the regulation of GLT-1 and xc- plays a role in the development of cerebral tolerance to ischemia and that this regulation may be a novel approach in the therapy of brain ischemia. PMID- 26861956 TI - Effect on post-cryopreserved semen characteristics of Holstein bulls of adding combinations of vitamin C and either catalase or reduced glutathione to Tris extender. AB - This study was undertaken to investigate the influence of adding combinations of vitamin C to Tris extender with either catalase or reduced glutathione on post cryopreserved semen characteristics of Holstein bulls for different preservation periods (cooling at 5 degrees C, 48 h, 1, 2 and 3 months post cryopreservation, PC). Seven Holstein bulls of 2.5-3 years of age were used in this experiment. Semen was collected via artificial vagina in one ejaculate per bull per week for the 7 week experimental period. Pooled semen was equally divided into three treatments using Tris extender. Combinations of vitamin C (2.5mM) were added with either catalase (100 IU/ml, T2) or reduced glutathione (2mM, T3) to Tris extender and comparisons in response were made with the control group (Tris extender, T1). Individual sperm motility (IM), viability (V), plasma membrane integrity (PMI), and acrosome integrity (AI) were assessed during all periods of the study along with Malondialdehyde (MDA) concentrations and freezing ability. The IM was greater (P <= 0.01) in the T2 as compared with the T1 group at all periods of the study. Furthermore, the IM were greater (P <= 0.01) in the T3 as compared with the T1 group at the 48 h time period and at 3 months PC. The V, PMI and AI were greater (P <= 0.01) in T2 and T3 as compared with the T1 group at all the experimental periods. The MDA was greater (P <= 0.01) in the T2 as compared with the T1 group at 3 months PC. In conclusion, there was improved semen quality if semen of Holstein bulls was collected and stored in combinations of vitamin C with either catalase (T2) or reduced glutathione (T3) being added to Tris extender. PMID- 26861958 TI - Homophobic Attitudes and Associated Factors Among Adolescents: A Comparison of Six Latin American Countries. AB - Homophobic attitudes are still very common in the world, although there are large differences between countries. This study analyzed the responses of almost 30,000 8th- and 9th-grade students from six countries who participated in the Latin American component of the International Civic and Citizenship Education Study. Higher levels of homophobia were found in the Dominican Republic, Guatemala, and Paraguay than in Chile, Colombia, and Mexico. Homophobic attitudes were positively associated with being male, having lower levels of empathy, spending less time with friends and the media, having aggressive attitudes, and being more religious, in particular non-Catholic Christian. PMID- 26861955 TI - An In Vitro Study of the Neurotoxic Effects of N-Benzylpiperazine: A Designer Drug of Abuse. AB - Recently, the number of new psychoactive substances has significantly increased. Despite the systematic introduction of prohibition in trade of medicinal products which mimic the effects of illegal drugs, the problem concerning this group of drugs is still important although knowledge about the mechanism of action of those types of substances is scarce. This study aimed to follow the neurotoxic effect of N-benzylpiperazine (BZP), the central nervous system psychostimulant, using the human cancer LN-18 cell model. The statistically significant elevation of LDH levels, increased mitochondrial membrane potential, decreased ATP and increased ROS production, increased levels of DNA damage marker (8-OHdG) and activation of caspases: -3 and -9 confirmed by Real-Time PCR imply the activation of mitochondrial proapoptotic pathways induced by BZP after 24 h incubation. This study is a novel, preliminary attempt to explain the toxicity of one of the most popular designer drug of abuse at the cellular level. PMID- 26861957 TI - Intra-articular injection of photo-activated platelet-rich plasma in patients with knee osteoarthritis: a double-blind, randomized controlled pilot study. AB - BACKGROUND: Improvements in knee osteoarthritis (OA) symptoms with platelet-rich plasma (PRP) have been attributed to its ability to modify intra-articular inflammatory processes. Photo-activation of peripheral blood also improves inflammatory mediators associated with OA, however combined photo-activated PRP (PA-PRP) has not been investigated. This pilot study assessed the feasibility, safety and symptomatic and functional change following injections of PA-PRP compared to hyaluronic acid (HA) in people with knee osteoarthritis (OA). METHODS: Thirty seven people with knee OA were enrolled in this double-blind randomized controlled pilot study set in a sports medicine clinic. Participants were randomly allocated to receive three injections of either PA-PRP or HA. The patients and the administering doctor were blinded to group allocation. Outcomes included recruitment and safety data, 100 mm visual analogue pain score (VAS), the Knee Osteoarthritis Outcome Score (KOOS), Knee Quality of Life (KQoL) scale, maximum hopping distance and number of knee bends in 30 s at four and 12 weeks. RESULTS: Twenty three (62 %) participants met the inclusion criteria, of which 12 (32 %) were randomized to the PA-PRP group and 11 (30 %) to the HA group. Two participants did not complete the intervention and two withdrew following their first assessment. Minor pain and swelling during the injection period was reported by two participants from the PA-PRP group. The PA-PRP group demonstrated significant improvements in the VAS (p < 0.01, ETA = 0.686), KOOS Pain (p < 0.05, ETA = 0.624), KQoL Physical (p < 0.05, ETA = 0.706) and KQoL Emotional subscales (p < 0.05, ETA = 0.715) at four and 12 weeks. The PA-PRP group also significantly improved hoping (p < 0.05, ETA = 0.799) and knee bends (p < 0.01, ETA = 0.756) at four or 12 weeks. The HA group showed improvements on only the KOOS Function subscale at 12 weeks (p < 0.01, ETA = 0.602). After controlling for baseline values, there were no significant between-group differences at either time-point. CONCLUSIONS: This study provides proof-of-concept evidence concerning the feasibility and safety of PA-PRP injections necessary to inform a larger clinical trial in people with knee OA. Our preliminary results also suggest PA-PRP improves self-reported pain, symptoms and lower extremity function, however no between-group differences were found. Photo-activated PRP may provide a safe and effective novel treatment for knee OA. TRIAL REGISTRATION: ACTRN12611000651987. PMID- 26861959 TI - Structure modeling and functional analysis of recombinant dextransucrase from Weissella confusa Cab3 expressed in Lactococcus lactis. AB - The dextransucrase gene from Weissella confusa Cab3, having an open reading frame of 4.2 kb coding for 1,402 amino acids, was amplified, cloned, and expressed in Lactococcus lactis. The recombinant dextransucrase, WcCab3-rDSR was expressed as extracellular enzyme in M17 medium with a specific activity of 1.5 U/mg which after purification by PEG-400 fractionation gave 6.1 U/mg resulting in 4-fold purification. WcCab3-rDSR was expressed as soluble and homogeneous protein of molecular mass, approximately, 180 kDa as analyzed by SDS-PAGE. It displayed maximum enzyme activity at 35 degrees C at pH 5.0 in 50 mM sodium acetate buffer. WcCab3-rDSR gave Km of 6.2 mM and Vm of 6.3 umol/min/mg. The characterization of dextran synthesized by WcCab3-rDSR by Fourier transform infrared and nuclear magnetic resonance spectroscopic analyses revealed the structural similarities with the dextran produced by the native dextransucrase. The modeled structure of WcCab3-rDSR using the crystal structures of dextransucrase from Lactobacillus reuteri (protein data bank, PDB id: 3HZ3) and Streptococcus mutans (PDB id: 3AIB) as templates depicted the presence of different domains such as A, B, C, IV, and V. The domains A and B are circularly permuted in nature having (beta/alpha)8 triose phosphate isomerase-barrel fold making the catalytic core of WcCab3-rDSR. The structure superposition and multiple sequence alignment analyses of WcCab3 rDSR with available structures of enzymes from family 70 GH suggested that the amino acid residue Asp510 acts as a nucleophile, Glu548 acts as a catalytic acid/base, whereas Asp621 acts as a transition-state stabilizer and these residues are found to be conserved within the family. PMID- 26861960 TI - Neck Muscular Strength, Training, Performance and Sport Injury Risk: A Review. AB - The neck musculature has an essential role in positioning and stabilising the head and may influence sport performance and injury risk. The objectives of this review are to (1) compare the neck strength of different athletes; (2) report on the outcomes of training programmes; (3) explore the association between neck strength and head stabilisation; (4) examine the relationship between neck strength and sport injury risk; and (5) identify areas for future research. There was a difference in strength between different player positions in football codes, gender and age. Detected differences were partly attributed to variation in neck muscle mass. Neck strength training programmes were generally shown to be effective for untrained and trained participants using dynamic or isometric actions and various types of resistance devices. There was a wide range of reported increases in neck strength; the smallest gains were usually for programmes that utilised lower intensity or frequency. There was limited evidence that greater isometric strength or dynamic training was associated with better head stabilisation during low-level force application, while there is direct evidence of an association between neck isometric training or strength and injury risk. A retrospective analysis of professional rugby union players revealed that isometric training reduced match-related cervical spine injuries and a prospective study found that greater overall isometric neck strength reduced concussion risk in high school athletes. Recommendations for future research include substantiating the link between neck strength and sport injury risk and assessing the effectiveness of neck plyometric and perturbation training on stabilisation and injury risk. PMID- 26861961 TI - Differences in hospital attendance for anaphylaxis between immigrants and non immigrants: a cohort study. AB - BACKGROUND: The impact of migration on the risk of anaphylaxis remains unknown. We hypothesized that non-Western immigrants have a lower incidence of anaphylaxis compared to Danish-born. We investigated variations in hospital attendance for anaphylaxis between immigrants and Danish-born including time- and age- trends. METHODS: A register-based, historical prospective cohort design. Refugees or family reunified immigrants (n = 127 250) who, between January 1, 1994 and December 31, 2010, obtained residency permits in Denmark were included and matched in a 1 : 6 ratio on age and sex with Danish-born individuals (n = 740 600). Personal identification numbers were cross-linked to the Danish National Patient Registry identifying all first-time hospital attendances for anaphylaxis from January 1, 1994 and December 31, 2010. Incidence rate ratios were estimated, stratified for sex and region of birth, adjusting for age using a Cox regression model including the influence of duration of residence and age when residence was obtained. RESULTS: In total 1053 hospital attendances for anaphylaxis were identified: 89 among non-Western immigrants, 9 among Western immigrants and 955 among Danish-born patients. Both male (RR = 0.65; 95%CI: 0.46;0.90) and female (RR = 0.64; 95%CI: 0.48;0.85) non-Western immigrants had a significantly lower risk ratio of hospital attendance for anaphylaxis compared to Danish-born. Compared to Danish-born, non-Western immigrants living in Denmark during the entire follow-up period also showed a decreased risk (RR = 0.65; 95%CI: 0.34;1.25). Compared to Danish-born, non-Western immigrants who obtained residence permission as children had a decreased risk of hospital attendance for anaphylaxis (RR = 0.48; 95%CI: 0.25;0.91). CONCLUSION: This Danish register-based study using nationwide data revealed fewer hospital attendances for anaphylaxis among non-Western immigrants compared to Danish-born; however this protection was lost over time. PMID- 26861962 TI - Lipid Rafts Disruption Increases Ochratoxin A Cytotoxicity to Hepatocytes. AB - Lipid rafts are microdomains in plasma membrane and can mediate cytotoxicity. In this study, the role of lipid rafts in ochratoxin A-induced toxicity was investigated using Hepatoblastoma Cell Line HepG-2 cells. Disruption of cholesterol-containing lipid rafts enhanced Ochratoxin A (OTA) toxicity, as shown by increased lactate dehydrogenase leakage, increased reactive oxygen species level and reduction of superoxide dismutase activity in a time-dependent manner. Isobaric tags for relative and absolute quantitation-based proteomics of the cell membranes showed that nearly 85.5% proteins were downregulated by OTA, indicating that OTA inhibited the membrane protein synthesis. Most of altered proteins were involved in Gene Ontology "transport", "cell adhesion" and "vesicle-mediated transport". In conclusion, lipid rafts play a key role in OTA-induced cytotoxicity. This study provides insight into how OTA toxicity is regulated by the plasma membrane, especially the lipid rafts. PMID- 26861963 TI - Modeling Online Health Information-Seeking Behavior in China: The Roles of Source Characteristics, Reward Assessment, and Internet Self-Efficacy. AB - The outbreak of severe acute respiratory syndrome (SARS) in 2003 marked the explosion of health information seeking online in China and the increasing emergence of Chinese health websites. There are both benefits and potential hazards of people's online health information seeking. This article intended to test part of Wilson's second model of information behavior, including source characteristics and activating mechanisms, and to identify the relationships among perceived access, perceived expertise credibility, reward assessment, Internet self-efficacy, and online health information-seeking behavior. Data were drawn from face-to-face surveys and an online survey of health information seekers (N = 393) in China. The results showed that source characteristics predicted activating mechanisms, which in turn predicted online health information-seeking behavior. Activating mechanisms, that is, reward assessment and Internet self-efficacy, mediated the relationship between source characteristics (i.e., access and credibility) and online health information seeking behavior. Strategies for improving information access, expertise credibility, and Internet self-efficacy are discussed in order to maximize the benefits of online health information seeking and to minimize the potential harm. PMID- 26861964 TI - First French live-birth after oocyte vitrification performed before chemotherapy for fertility preservation. PMID- 26861965 TI - Sperm retrieval and concomitant tumor resection in azoospermic men with congenital adrenal hyperplasia and bilateral testicular adrenal rest tumors: a case report. AB - PURPOSE: The objective of this study was to offer a new treatment approach for sperm retrieval simultaneously with tumor resection in azoospermic men with congenital adrenal hyperplasia (CAH), orchialgia, and bilateral testicular adrenal rest tumors (TARTs) who fail to respond to medical treatment. METHODS: This is a retrospective chart review from a couple's fertility center. RESULTS: Between May 2013 and May 2015, two azoospermic men with CAH and bilateral TARTs, with orchialgia, and desire to conceive underwent bilateral TART resection in the same surgical setting as sperm retrieval after remaining azoospermic with normalization of gonadotropins with treatment with human chorionic gonadotropin (hCG). Both men had adequate sperm retrieved for in vitro fertilization/intracytoplasmic sperm retrieval (IVF/ICSI) at the time of bilateral TART resections. They had complete TART resections with resolution of orchialgia. The wife of one patient had a successful pregnancy with use of retrieved sperm resulting in a live birth, and the sperm from the other man is cryopreserved for future use. CONCLUSIONS: It is feasible to perform successful sperm retrieval simultaneously with TART resection in azoospermic men with CAH after medical treatments with persistent azoospermia, rather than subjecting these men to multiple invasive procedures. PMID- 26861966 TI - The impact of patient preselection on reported IVF outcomes. AB - We, in this manuscript, address the fact that increasing numbers of published studies in reproductive medicine selectively report outcomes for only favorably selected patients; while failing to note that, so reported outcome data,therefore, cannot be applied to unselected patient populations. Almost all favorable patient selection methods, starting with prolonged embryo culture to blastocyst stage, have, thus, been widely misrepresented in the literature since they almost universally report outcomes only in reference to embryo transfer. These outcome reports, however, do not include outcomes for poorer prognosis patients who do not reach embryo transfer. Study outcomes are universally applicable only if performed in unselected patient populations and reported with reference point cycle start (intent to treat). All other studies greatly exaggerate clinical pregnancy and live birth rates if applied to general populations, unless specifically noting that they can be extrapolated only to women who reach embryo transfer. PMID- 26861967 TI - High body clearance and low oral bioavailability of alantolactone, isolated from Inula helenium, in rats: extensive hepatic metabolism and low stability in gastrointestinal fluids. AB - Alantolactone (ALA) is a major bioactive sesquiterpene lactone present in the roots of Inula helenium L. (Asteraceae) which has been used widely in traditional medicine against various diseases such as asthma, cancer and tuberculosis. The pharmacologic activities of alantolactone have been well characterized, yet information on the physicochemical and pharmacokinetic properties of alantolactone and their mechanistic elucidation are still limited. Thus, this study aims to investigate the oral absorption and disposition of alantolactone and their relevant mechanisms. Log P values of alantolactone ranged from 1.52 to 1.84, and alantolactone was unstable in biological samples such as plasma, urine, bile, rat liver microsomes (RLM) and simulated gastrointestinal fluids. The metabolic rate of alantolactone was markedly higher in rat liver homogenates than in the other tissue homogenates. A saturable and concentration-dependent metabolic rate profile of alantolactone was observed in RLM, and rat cytochrome P450 (CYP) 1 A, 2C, 2D and 3 A subfamilies were significantly involved in its hepatic metabolism. Based on the well-stirred model, the hepatic extraction ratio (HER) was estimated to be 0.890-0.933, classifying alantolactone as a drug with high HER. Moreover, high total body clearance (111 +/- 41 ml/min/kg) and low oral bioavailability (0.323%) of alantolactone were observed in rats. Taken together, the present study demonstrates that the extensive hepatic metabolism, at least partially mediated by CYP, is primarily responsible for the high total body clearance of alantolactone, and that the low oral bioavailability of alantolactone could be attributed to its low stability in gastrointestinal fluids and a hepatic first-pass effect in rats. Copyright (c) 2016 John Wiley & Sons, Ltd. PMID- 26861968 TI - Neurovascular Stains in Two Girls with Neurofibromatosis 1. AB - We report two girls, ages 9 and 17 years, with a clinical diagnosis of neurofibromatosis 1 (NF-1) who presented with ill-defined, blanchable, erythematous patches on the dorsal feet and ankles. We hypothesized that these patches were a rare cutaneous finding in NF-1 that exist on a clinical and histopathologic spectrum with previously described NF-1 vascular lesions including blue-red macules and skin ulceration due to NF-1 vasculopathy. We suggest that these lesions be called neurovascular stains (NVSs) to unify their clinical and histopathologic features. PMID- 26861969 TI - How Does Outcomes Research Help Advance Our Knowledge of Patient Outcomes in Hepatopancreaticobiliary Surgery? AB - Randomized controlled trials have historically been regarded as the gold standard of modern clinical research tools, allowing us to elucidate the efficacy of novel therapeutics in an unparalleled manner. However, when attempting to generalize trial results to broader populations, it becomes apparent that the unexplained outcome variability exists among treatment recipients, suggesting that randomized controlled trials harbor inherent limitations. Herein, we explore the benefits of health services (outcomes) research utilization in addressing variation in patient outcomes following surgical intervention in the non-randomized setting, with a specific focus on hepatopancreaticobiliary surgery outcomes. To achieve this, we have constructed a framework that outlines the complex interactions existing between therapeutic, patient, and provider factors that subsequently lead to variation in outcomes. By exploring examples in the current literature, we have highlighted the areas where the knowledge is currently lacking and can be further strengthened through the application of outcomes research. Furthermore, we have attempted to demonstrate the utility of alternative study designs in the investigation of novel clinical questions currently unanswered in the field of hepatopancreaticobiliary surgery. PMID- 26861971 TI - Alcohol prices, taxes, and alcohol-related harms: A critical review of natural experiments in alcohol policy for nine countries. AB - OBJECTIVE: Evidence for alcohol-price policy relies heavily on aggregate econometric studies for the United States. Prior reviews of prices and alcohol related harms include only a few studies based on natural experiments. This study provides a comprehensive review of natural experiments for a wide variety of harms from studies published during 2003 to 2015. We examine policy changes that importantly affected alcohol taxes and prices, and related changes in availability. METHODS: Forty-five studies met inclusion criteria, covering nine countries: Australia, Denmark, Finland, Hong Kong, Iceland, Russia, Sweden, Switzerland, and United States. Some studies cover more than one harm or country, and there are 69 outcomes for review. Summaries are provided for five outcome groups: alcohol-related mortality and hospitalizations; assaults and other crime; drink-driving; intoxication; and survey-indexes for dependency. The review notes both positive/mixed results and negative/null results. RESULTS: Findings indicate that changes in taxes and prices have selective effects on harms. Mortality outcomes are positive for liver disease and older persons, especially in Finland and Russia. Mostly null results for assaults and drink-driving are found for five countries. Intoxication results for Nordic countries are mixed for selective subpopulations. Results for survey indexes are mixed, with no strong pattern of outcomes within or across countries. CONCLUSION: Prior reviews stress taxes as a comprehensive and cost-effective intervention for addressing alcohol-related harms. A review of natural experiments indicates the confidence placed on this measure is too high, and natural experiments in alcohol policy had selective effects on various subpopulations. PMID- 26861970 TI - Iron chelation therapy of transfusion-dependent beta-thalassemia during pregnancy in the era of novel drugs: is deferasirox toxic? AB - The life expectancy of thalassemic patients has increased, and now approaches that of healthy individuals, thanks to improved treatment regimens. However, pregnancy in women with beta-Thalassemia MUajor remains a challenging condition. Recent advances in managing this haemoglobinopathy offer the potential for safe pregnancies with favorable outcome. However, clinical data regarding the use of chelation therapy during pregnancy are limited, and it is unclear whether these agents impose any risk to the developing fetus. Successful pregnancies following unintentional treatment with deferoxamine or deferasirox have rarely been reported. Generally, chelators are not recommended during pregnancy. Regarding the new oral chelators, data on fetotoxicity are lacking. In the present study, we describe the evolution and successful outcome of nine pregnancies in six Greek thalassemic women who received deferasirox inadvertently during early pregnancy, and review the literature regarding fetal anomalies due to chelators. Use of chelation before embarking upon a non-programmed pregnancy remains a difficult and unresolved question. In our study, chelation treatment during pregnancy did not prevent the delivery of healthy children. Nonetheless, the use of deferasirox is contraindicated in pregnant women, based on the product label. Deferasirox should only be used during pregnancy if the potential benefit outweighs the potential fetal risk. PMID- 26861972 TI - Consumer preferences for over-the-counter drug retailers in the reregulated Swedish pharmacy market. AB - Following a large regulatory reform in 2009, which ended the state's pharmacy monopoly, non-pharmacy retailers in Sweden today sell certain over-the-counter (OTC) drugs. The aim of this study was to investigate consumer preferences regarding OTC drug retailers and the reasons for choosing a pharmacy versus non pharmacy retailer. We conducted a web survey aimed at Swedish adults. Out of a stratified sample of 4058 persons, 2594 agreed to take part (48% women; mean age: 50.3 years). Questions related to OTC drug use, retailer choice and factors affecting the participants' preferences for OTC drug retailers. Logistic regression was conducted to analyse OTC drug use and reasons for retailer choice in relation to sex, age and education. Nine in ten participants reported OTC drug use in the 6 months prior to the study. For their last OTC purchase, 76% had gone to a pharmacy, 20% to a grocery shop and 4% to a convenience store, gas station or online. Geographic proximity, opening hours and product range were reported as the most important factors in retailer choice. Counselling by trained staff was important to 57% of participants. The end of the state's pharmacy monopoly and the increase in number of pharmacies seem to have impacted more on Swedish consumers' purchase behaviours compared with the deregulation of OTC drug sales. PMID- 26861973 TI - Assessing public health job portals over the internet. AB - AIMS: The objective of our study was to search existing public health job websites over the internet and describe the challenges related to finding these job websites. METHOD: An internet search was conducted using different search engines, including Google, Yahoo and Bing, with several keywords including: Public Health Jobs, Epidemiology Jobs, Biostatistics Jobs, Health Policy and Management Jobs, Community Health Jobs, Health Administration Jobs, Nutrition Jobs, Environmental and Occupational Health Science Jobs, GIS Jobs, and Public Health Informatics Jobs. We recorded the first 20 websites that appeared in the results of each keyword search, thus generating 600 URLs. Duplicate sites and non functional sites were excluded from this search, allowing analysis of unique sites only. RESULTS: The initial search resulted in 600 websites of which there were 470 duplicates. More than half of the website categories were ".com" (54%; n = 323) followed by ".gov" (19%; n = 111) and ".edu" 15% (n = 90). Results of our findings showed 194 unique websites resulting from a search of 600 website links. More than half of them had actual public health or its related jobs (56%; n = 108). CONCLUSION: There is a need to establish standard occupational classification categories for the public health workforce. PMID- 26861974 TI - FGFR3 and Cyclin D3 as urine biomarkers of bladder cancer recurrence. AB - AIM: To assess the diagnostic performance of FGFR3 and Cyclin D3 urinary protein levels in detecting bladder cancer recurrence. PATIENTS & METHODS: Urine of 321 patients in follow-up for bladder cancer and 150 non-neoplastic urine controls was included. Cytology, cystoscopy and FGFR3 and Cyclin D3 expression by western blot were performed. RESULTS: One hundred ten (34.3%) patients had evidence of tumor recurrence. The sensitivity and specificity of cytology/cystoscopy was 80 and 84%, and for FGFR3/Cyclin D3 was of 73 and 90%. CONCLUSION: Combined urinary FGFR3/Cyclin D3 expression shows improved detection rates for bladder cancer recurrence with high specificity and sensitivity, and within the same range of detection shown by cystoscopy, therefore supporting its potential use as noninvasive diagnostic biomarker for bladder cancer recurrence. PMID- 26861975 TI - Action of antimicrobial photodynamic therapy on heterotypic biofilm: Candida albicans and Bacillus atrophaeus. AB - The increase in survival and resistance of microorganisms organized in biofilms demonstrates the need for new studies to develop therapies able to break this barrier, such as photodynamic therapy, which is characterized as an alternative, effective, and non-invasive treatment. The objective was to evaluate in vitro the effect of antimicrobial photodynamic therapy on heterotypic biofilms of Candida albicans and Bacillus atrophaeus using rose bengal (12.5 MUM) and light-emitting diode (LED) (532 nm and 16.2 J). We used standard strains of B. atrophaeus (ATCC 9372) and C. albicans (ATCC 18804). The biofilm was formed in the bottom of the plate for 48 h. For the photodynamic therapy (PDT) experimental groups, we added 100 MUL of rose bengal with LED (P+L+), 100 MUL of rose bengal without LED (P+L ), 100 MUL of NaCl 0.9 % solution with LED (P-L+), and a control group without photosensitizer or LED (P-L-). The plates remained in agitation for 5 min (pre irradiation) and were irradiated with LED for 3 min, and the biofilm was detached using an ultrasonic homogenizer for 30 s. Serial dilutions were plated in BHI agar and HiChrom agar and incubated at 37 degrees C/48 h. There was a reduction of 33.92 and 29.31 % of colony-forming units per milliliter (CFU/mL) for C. albicans and B. atrophaeus, respectively, from the control group to the group subjected to PDT. However, statistically significant differences were not observed among the P+L+, P+L-, P-L+, and P-L- groups. These results suggest that antimicrobial photodynamic therapy using rose bengal (12.5 MUM) with a pre irradiation period of 5 min and LED for 3 min was not enough to cause a significant reduction in the heterotypic biofilms of C. albicans and B. atrophaeus. PMID- 26861977 TI - Pulsed dye laser treatment of paediatric port wine stains-variation of practice in the UK (NHS). PMID- 26861976 TI - Topical anaesthetic effects on skin vasculature with potential implications for laser treatment. AB - Laser treatment of vascular lesions is affected by parameters including the diameter and depth of the vessels and flow within the vessels. Topical anaesthetics are in common use prior to laser treatment but may have effects on vessel parameters and, subsequently, the efficacy of laser treatment. Eleven patients with capillary vascular malformations were investigated for vessel diameter before and after elective application of a topical anaesthetic, Eutectic Mixture of Local Anaesthetics (EMLA) (AstraZeneca) or Ametop (S&N Health), prior to pulsed dye laser treatment. EMLA contains 2.5% lidocaine ad 2.5% prilocaine, and Ametop gel contains 4% tetracaine. Patients' capillary malformations were assessed using confocal laser scanning microscopy (CLSM) (Vivascope 1500 Mavig GmbH, Munich). Six of the 11 patients recruited had EMLA topical anaesthetic, and five had Ametop. Four hundred twenty-one diameters were measured. The mean vessel diameter was 50.87 MUm. Previous laser treatments undergone by each patient were noted to exclude this as a confounding variable, and no significant difference was found between topical anaesthetic groups. Statistical calculations were made using GenStat and Minitab. There is no evidence that Ametop affects mean diameter (p value is 0.361). EMLA reduces the mean diameter of vessels (p = 0.002), with a 27% reduction in post-EMLA diameter. This study demonstrates that the use of EMLA cream has a statistically significant reduction vessel diameter. As it is known that vessel diameter is important for the response of laser treatment, the use of EMLA may affect outcome. PMID- 26861978 TI - Lipid volume fraction in atherosclerotic plaque phantoms classified under saline conditions by multispectral angioscopy at near-infrared wavelengths around 1200 nm. AB - To identify high-risk atherosclerotic lesions, we require detailed information on the stability of atherosclerotic plaques. In this study, we quantitatively classified the lipid volume fractions in atherosclerotic plaque phantoms by a novel angioscope combined with near-infrared multispectral imaging. The multispectral angioscope was operated at peak absorption wavelengths of lipid in vulnerable plaques (1150, 1200, and 1300 nm) and at lower absorption wavelengths of water. The potential of the multispectral angioscope was demonstrated in atherosclerotic plaque phantoms containing 10-60 vol.% lipid and immersed in saline solution. The acquired multispectral data were processed by a spectral angle mapper algorithm, which enhanced the simulated plaque areas. Consequently, we classified the lipid volume fractions into five categories (0-5, 5-15, 15-30, 30-50, and 50-60 vol.%). Multispectral angioscopy at wavelengths around 1200 nm is a powerful tool for quantitatively evaluating the stability of atherosclerotic plaques based on the lipid volume fractions. PMID- 26861980 TI - Comparison of clinical efficacy and complications between Q-switched alexandrite laser and Q-switched Nd:YAG laser on nevus of Ota: a systematic review and meta analysis. AB - Although the application of Q-switched lasers on nevus of Ota (OTA) is well demonstrated, debates about clinical option between Q-switched alexandrite laser (QSA) and Q-switched Nd:YAG laser (QSNY) still remain. This systematic review and meta-analysis estimated the overall successful rate of OTA pigment clearance and complication rate of QSA and QSNY and evaluated which laser could produce a better result. English articles evaluating pigment clearance and complications of QSA and/or QSNY on OTA were screened through predetermined inclusion and exclusion criteria and analyzed. The successful rate of pigment clearance and complication rate of QSA and QSNY were respectively calculated using a random effects or fixed-effects model, depending on the heterogeneity of the included studies. The successful rate and complication rate of QSA and QSNY were compared statistically. Of the 140 articles searched, 13 met inclusion criteria. Totally, 2153 OTA patients treated by QSA and 316 patients treated by QSNY were analyzed. In QSA and QSNY groups, respectively, the successful rate of OTA pigment clearance was 48.3% (95% confidence interval (CI) 19.9-76.8%) and 41% (95% CI 9.7 72.2%), while the complication rate was 8.0% (95% CI 3.9-12.2%) and 13.4% (95% CI 7.7-19.0%). When compared with QSNY, QSA had a significantly higher successful rate (P = 0.017), and a lower complication rate (P = 0.000). According to this review, QSA may surpass QSNY in treatment for OTA as it had a superior successful rate of pigment clearance and a lower complication rate than QSNY did. PMID- 26861979 TI - Effect of size, concentration, and type of spherical gold nanoparticles on heat evolution following laser irradiation using tissue-simulating phantoms. AB - Photothermal therapy has recently gained a considerable attention particularly after the revolution of nanomaterials and nanotechnology. The aim of the present study is to assess the optimal photothermal response through investigating some effective parameters of spherical gold nanoparticles (AuNPs), e.g., type, size, and concentration, as a preclinical study for efficient photothermal treatment. Tissue-simulating phantoms based on agar and water media incorporated with two different types of AuNPs, spherical Au particles capped with citrate or spherical Au core-silica shell NPs, were built. Heat evolution for each NP type was recorded in the phantom matrix with different particle sizes at various concentrations following exposure to low laser power (irradiance 35 mW/cm(2)) and emitting at lambda = 532 nm. Our results demonstrated that AuNPs capped with citrate recorded higher temperature elevations than those capped with silica shell. Particles with smaller sizes produced more heating effect than those having larger sizes. Also, higher temperatures were recorded at a critical concentration of NPs. Exponential decay constants based on theoretical calculations demonstrated that laser attenuation increases with the continuous increase of particle size and concentration. PMID- 26861981 TI - Time course of apoptosis induced by photodynamic therapy with PsD007 in LT12 acute myeloid leukemia cells. AB - Apoptosis is one of the major mechanisms of photodynamic therapy (PDT) that leads to tumor degradation. Apoptosis-related genes and proteins function in a certain order and timing in the complex network of apoptosis. To further understanding of the apoptotic mechanism of PDT, this research examined the time course of apoptosis from PsD007 (a second-generation photosensitizer developed in China) induced PDT on the rat acute myeloid leukemia cell line LT12. MTT was used to detect the temporal dynamic of PDT killing effects and identified the "apoptotic window" of 2-24 h. Apoptosis showed a basal peak at 2 h, and the duration of apoptosis depended on PDT dose, which disappeared quickly at low concentrations but lasted to higher levels to 6 or 12 h at high concentrations as detected by flow cytometry. High-content imaging confirmed these results. An 84-gene apoptosis PCR array identified 15 genes with an expression level change of over twofold at 6 h post-PDT. Nine apoptosis-related genes showed changes in expression at 2-12 h after PDT. TNF family genes TNF and FASLG showed a maximal change of 3.47- and 4.42-fold from baseline. Key apoptosis proteins such as activated caspases showed strong up-regulation after PDT, with the expression peaks of cleaved caspase-7, caspase-9 and PARP at 4-6 h, and cleaved caspase-3 delayed to 6-12 h. Our findings help clarify the time course of apoptosis events in response to PDT treatment in a leukemia cell line and may help contribute to the clinical application of PDT in leukemia treatment. PMID- 26861982 TI - Low-level laser irradiation effect on endothelial cells under conditions of hyperglycemia. AB - Diabetes mellitus is considered to be a very serious lifestyle disease leading to cardiovascular complications and impaired wound healing observed in the diabetic foot syndrome. Chronic hyperglycemia is the source of the endothelial activation. The inflammatory process in diabetes is associated with the secretion of inflammatory cytokines by endothelial cells, e.g., tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6). The method of phototherapy using laser beam of low power (LLLT-low-level laser therapy) effectively supports the conventional treatment of diabetic vascular complications such as diabetic foot syndrome. The aim of our study was to evaluate the effect of low-power laser irradiation at two wavelengths (635 and 830 nm) on the secretion of inflammatory factors (TNF-alpha and IL-6) by the endothelial cell culture-HUVEC line (human umbilical vein endothelial cell)-under conditions of hyperglycemia. It is considered that adverse effects of hyperglycemia on vascular endothelial cells may be corrected by the action of LLLT, especially with the wavelength of 830 nm. It leads to the reduction of TNF-alpha concentration in the supernatant and enhancement of cell proliferation. Endothelial cells play an important role in the pathogenesis of diabetes; however, a small number of studies evaluate an impact of LLLT on these cells under conditions of hyperglycemia. Further work on this subject is warranted. PMID- 26861983 TI - The effect of low-level laser therapy on oxidative stress and functional fitness in aged rats subjected to swimming: an aerobic exercise. AB - The aim of the present study was to determine whether low-level laser therapy (LLLT) in conjunction with aerobic training interferes with oxidative stress, thereby influencing the performance of old rats participating in swimming. Thirty Wistar rats (Norvegicus albinus) (24 aged and six young) were tested. The older animals were randomly divided into aged-control, aged-exercise, aged-LLLT, aged LLLT/exercise, and young-control. Aerobic capacity (VO2max(0.75)) was analyzed before and after the training period. The exercise groups were trained for 6 weeks, and the LLLT was applied at 808 nm and 4 J energy. The rats were euthanized, and muscle tissue was collected to analyze the index of lipid peroxidation thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. VO2 (0.75)max values in the aged-LLLT/exercise group were significantly higher from those in the baseline older group (p <0.01) and the LLLT and exercise group (p <0.05). The results indicate that the activities of CAT, SOD, and GPx were higher and statistically significant (p <0.05) in the LLLT/exercise group than those in the LLLT and exercise groups. Young animals presented lesser and statistically significant activities of antioxidant enzymes compared to the aged group. The LLLT/exercise group and the LLLT and exercise group could also mitigate the concentration of TBARS (p > 0.05). Laser therapy in conjunction with aerobic training may reduce oxidative stress, as well as increase VO2 (0.75)max, indicating that an aerobic exercise such as swimming increases speed and improves performance in aged animals treated with LLLT. PMID- 26861984 TI - Minimally invasive, non-ablative Er:YAG laser treatment of stress urinary incontinence in women--a pilot study. AB - The study presents an assessment of mechanism of action and a pilot clinical study of efficacy and safety of the Er:YAG laser for the treatment of stress urinary incontinence (SUI). The subject of this study is a treatment of SUI with a 2940 nm Er:YAG laser, operating in a special SMOOTH mode designed to increase temperature of the vaginal mucosa up to maximally 60-65 degrees C without ablating the epidermis. Numerical modelling of the temperature distribution within mucosa tissue following an irradiation with the SMOOTH mode Er:YAG laser was performed in order to determine the appropriate range of laser parameters. The laser treatment parameters were further confirmed by measuring in vivo temperatures of the vaginal mucosa using a thermal camera. To investigate the clinical efficacy and safety of the SMOOTH mode Er:YAG laser SUI treatment, a pilot clinical study was performed. The study recruited 31 female patients suffering from SUI. Follow-ups were scheduled at 1, 2, and 6 months post treatment. ICIQ-UI questionnaires were collected as a primary trial endpoint. Secondary endpoints included perineometry and residual urine volume measurements at baseline and all follow-ups. Thermal camera measurements have shown the optimal increase in temperature of the vaginal mucosa following treatment of SUI with a SMOOTH mode Er:YAG laser. Primary endpoint, the change in ICIQ-UI score, showed clinically relevant and statistically significant improvement after all follow-ups compared to baseline scores. There was also improvement in the secondary endpoints. Only mild and transient adverse events and no serious adverse events were reported. The results indicate that non-ablative Er:YAG laser therapy is a promising minimally invasive non-surgical option for treating women with SUI symptoms. PMID- 26861985 TI - Echocardiography-guided percutaneous per-ventricular laser ablation of ventricular septum: in vivo study in a canine model. AB - Surgical myectomy and ethanol ablation are established intervention strategies for left ventricular outflow obstruction in hypertrophic cardiomyopathy. Safety and efficacy limitations of these interventions call for a minimally invasive, potentially safer, and more efficacious strategy. In this study, we aimed to evaluate the feasibility of echocardiography-guided percutaneous per-ventricular laser ablation of a ventricular septum in a canine model. Six domestic dogs were chosen for the study. A 21G needle was inserted into the right ventricle with its tip reaching the targeted basal to mid-septum, after which laser ablation was performed as follows: 1-W laser for 3 min (180 J) at the basal segment and 5 min (300 J) at middle segment of the septum, respectively. Echocardiography, blood chemistry tests, and pathology examination were performed to assess the results of laser ablation. No death or major complications, i.e., tamponade, pericardial effusion, or ventricular fibrillation, occurred. The laser-ablated areas were well demarcated in the results of the pathological examination. The diameters of the ablated regions were 4.42 +/- 0.57 and 5.28 +/- 0.83 mm for 3 and 5 min ablation, respectively. Pre-ablation and post-ablation, cardiac enzymes were found to increase significantly while no significant differences were found among M-mode, 2D (LVEF), pulsed-wave (PW) Doppler, and tissue Doppler imaging (TDI) measurements. Contrast echocardiography confirmed the perfusion defects in the ablated regions. Microscopically, the ablated myocardium showed coagulative changes and a sparse distribution of disappearing nuclei and an increase in eosinophil number were observed. Our study suggests that percutaneous and per ventricular laser ablation of the septum is feasible, potentially safe and efficacious, and warrants further investigation and validation. PMID- 26861986 TI - Effects of hair removal alexandrite laser on biometric parameters of the skin. AB - The effects of alexandrite laser (AL) on skin parameters such as melanin content, skin layer depth, elasticity, and density have not been investigated through biometric methods. We aim to assess the effect of AL on the skin parameters through biometric devices to determine whether it has positive effects on treated region. In this pretest-posttest study, we recruited patients who attended Laser Clinic of Skin and Stem Cell Research Center, Tehran University of Medical Sciences, Tehran, Iran, from January through December 2014. Patients had to be free of any dermatologic conditions and lesion at the site of treatment or any contraindication to laser therapy. Baseline measurements were performed and patients received four sessions of AL therapy (spot size, 12 mm; fluence, 12 J/cm(2); and pulse width, 5 Hz) with 4-week intervals. Four weeks after the last treatment session, the same parameters were assessed that included skin color, transepidermal water loss (TEWL), dermis and epidermis density and depth (through skin ultrasonography), melanin content, erythema intensity, and skin elasticity. Biometric parameters of 33 patients (27 females [81.8%]), with mean (SD) age of 35.7 (9.5) years were evaluated. The mean percent changes of skin parameters were as follows: skin color, 5.88% through Visioface and by 56.8% through Colorimeter devices (became lighter); melanin content, -15.95%; TEWL, -2.96%; elasticity, +14.88%; dermis depth -19.01%; and dermis density, +1580.11% (P < 0.001 for changes in each parameter). AL could decrease melanin content of the skin and make the skin thinner while it could increase elasticity and density of epidermis and dermis, which might indicate increased collagen content of skin. PMID- 26861988 TI - Influence of lasing parameters on the cleaning efficacy of laser-activated irrigation with pulsed erbium lasers. AB - Laser-activated irrigation (LAI) using erbium lasers is an irrigant agitation technique with great potential for improved cleaning of the root canal system, as shown in many in vitro studies. However, lasing parameters for LAI vary considerably and their influence remains unclear. Therefore, this study sought to investigate the influence of pulse energy, pulse frequency, pulse length, irradiation time and fibre tip shape, position and diameter on the cleaning efficacy of LAI. Transparent resin blocks containing standardized root canals (apical diameter of 0.4 mm, 6% taper, 15 mm long, with a coronal reservoir) were used as the test model. A standardized groove in the apical part of each canal wall was packed with stained dentin debris. The canals were filled with irrigant, which was activated by an erbium: yttrium aluminium garnet (Er:YAG) laser (2940 nm, AT Fidelis, Fotona, Ljubljana, Slovenia). In each experiment, one laser parameter was varied, while the others remained constant. In this way, the influence of pulse energy (10-40 mJ), pulse length (50-1000 MUs), frequency (5-30 Hz), irradiation time (5-40 s) and fibre tip shape (flat or conical), position (pulp chamber, canal entrance, next to groove) and diameter (300-600 MUm) was determined by treating 20 canals per parameter. The amount of debris remaining in the groove after each LAI procedure was scored and compared among the different treatments. The parameters significantly (P < 0.05, Kruskal-Wallis) affecting debris removal from the groove were fibre tip position, pulse length, pulse energy, irradiation time and frequency. Fibre tip shape and diameter had no significant influence on the cleaning efficacy. PMID- 26861987 TI - Is there a protocol in experimental skin wounds in rats using low-level diode laser therapy (LLDLT) combining or not red and infrared wavelengths? Systematic review. AB - A systematic review addressing experiments with healing of skin wounds in rats using LLDLT with different active means seeking to identify a pattern in adjustments such as laser wavelength, power and fluency and analysing wound healing parameters, such as wound area, presence of fibroblasts, angiogenesis, leukocyte infiltration, epithelial coverage and antibacterial effect. It was perceived that a protocol does not exist in view of the wide variation in the use of power (9 to 500 mW) and fluency (1 to 60 J/cm2); however, between the different wavelengths, the highlight was the combined use of red and infrared wavelengths showing better results than when used alone. PMID- 26861989 TI - Anticoagulation in Patients With Cirrhosis: Caught Between a Rock-Liver and a Hard Place. AB - OBJECTIVE: To review current literature for anticoagulation in patients with cirrhosis and provide a summary of the effects of cirrhosis on the coagulation cascade, therapeutic monitoring through interpretation of antifactor Xa (anti Xa), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) as well as current prophylaxis and treatment recommendations in cirrhotic patients. METHODS: A systematic electronic literature search was conducted in PubMed using the key termsanticoagulation, warfarin, low-molecular weight heparin(LMWH),unfractionated heparin(UFH),target-specific oral anticoagulants, deep-vein thrombosis(DVT),pulmonary embolism(PE),portal vein thrombosis(PVT),venous thromboembolism, anti-Xa, activated partial thromboplastin time, anticoagulation therapeutic monitoring, coagulopathy, coagulation cascade, chronic liver disease, cirrhosis, anddecompensated liver disease STUDY SELECTION: Studies written in the English language from January 2000 to December 2015 were considered for this review article. All search results were reviewed, and the relevance of each article was determined by authors independently. CONCLUSIONS: Patients with cirrhosis are at higher risk for both bleeding and thrombosis related complications. Cirrhosis affects production of both procoagulant and anticoagulant factors, thus resulting in increased INR and aPTT levels and decreased anti-Xa levels. LMWH is the treatment of choice for the prevention and treatment of DVT/PE/PVT in patients with cirrhosis, and monitoring with anti-Xa levels for dose adjustment is not recommended. UFH is an alternative in cirrhotic patients for shorter-term use and in cases of severe renal dysfunction and/or hemodynamic instability. Cirrhotic patients on anticoagulation therapy should be monitored closely for signs and symptoms of bleeding and thrombosis. PMID- 26861990 TI - Treatment of Severe Alcohol Withdrawal. AB - OBJECTIVE: Approximately 50% of patients with alcohol dependence experience alcohol withdrawal. Severe alcohol withdrawal is characterized by seizures and/or delirium tremens, often refractory to standard doses of benzodiazepines, and requires aggressive treatment. This review aims to summarize the literature pertaining to the pharmacotherapy of severe alcohol withdrawal. DATA SOURCES: PubMed (January 1960 to October 2015) was searched using the search termsalcohol withdrawal, delirium tremens, intensive care, andrefractory Supplemental references were generated through review of identified literature citations. STUDY SELECTION AND DATA EXTRACTION: Available English language articles assessing pharmacotherapy options for adult patients with severe alcohol withdrawal were included. DATA SYNTHESIS: A PubMed search yielded 739 articles for evaluation, of which 27 were included. The number of randomized controlled trials was limited, so many of these are retrospective analyses and case reports. Benzodiazepines remain the treatment of choice, with diazepam having the most favorable pharmacokinetic profile. Protocolized escalation of benzodiazepines as an alternative to a symptom-triggered approach may decrease the need for mechanical ventilation and intensive care unit (ICU) length of stay. Propofol is appropriate for patients refractory to benzodiazepines; however, the roles of phenobarbital, dexmedetomidine, and ketamine remain unclear. CONCLUSIONS: Severe alcohol withdrawal is not clearly defined, and limited data regarding management are available. Protocolized administration of benzodiazepines, in combination with phenobarbital, may reduce the need for mechanical ventilation and lead to shorter ICU stays. Propofol is a viable alternative for patients refractory to benzodiazepines; however, the role of other agents remains unclear. Randomized, prospective studies are needed to clearly define effective treatment strategies. PMID- 26861991 TI - Evaluation of Herpes Zoster Vaccination in HIV-Infected Patients 50 Years of Age and Older. PMID- 26861992 TI - Reply: Management of De Novo CML and Imatinib-Induced Acute Rhabdomyolysis With the Second-Generation TKI, Dasatinib. PMID- 26861994 TI - Suppression of mitochondrial transcription initiation complexes changes the balance of replication intermediates of mitochondrial DNA and reduces 7S DNA in cultured human cells. AB - Analysis of replicating mammalian mitochondrial DNA (mtDNA) suggested that initiation of the replication occurs not only at the specific position, Ori-H but also across a broad zone in mtDNA. We investigated relationship of mitochondrial transcription initiation which takes place upstream of Ori-H and mtDNA replication initiation through analysing the effect of knockdown of mitochondrial transcription factor B2, TFB2M and mitochondrial RNA polymerase, POLRMT, components of the transcription initiation complexes in cultured human cells. Under the conditions where suppression of the transcription initiation complexes was achieved by simultaneous depletion of TFB2M and POLRMT, decrease of replication intermediates of mtDNA RITOLS replication mode accompanied reduction in mtDNA copy number. On the other hand, replication intermediates of coupled leading and lagging strand DNA replication, another proposed replication mode, appeared to be less affected. The findings support the view that the former mode involves transcription from the light strand promoter (LSP), and suggest that initiation of the latter mode is independent from the transcription and has distinct regulation. Further, knockdown of TFB2M alone caused significant decrease of 7S DNA, which implies that transcription initiation complexes formed at the LSP engage 7S DNA synthesis more frequently than the initiation of productive replication and transcription. PMID- 26861993 TI - Transforming growth factor-beta1 induces invasion ability of HSC-4 human oral squamous cell carcinoma cells through the Slug/Wnt-5b/MMP-10 signalling axis. AB - Molecular mechanism underlying the invasion of oral cancer cells remains to be clarified. We previously demonstrated that transforming growth factor-beta1 (TGF beta1) induces the expression of mesenchymal markers in human oral squamous cell carcinoma HSC-4 cells. Intriguingly, the expression of the epithelial-mesenchymal transition-related transcription factor Slug was also significantly upregulated upon TGF-beta1 stimulation. However, the mechanism by which Slug transduces the TGF-beta1-induced signal to enhance the invasiveness of HSC-4 cells is poorly understood. Proteomic analysis revealed that the expression of matrix metalloproteinase (MMP)-10 was upregulated in TGF-beta1-stimulated cells. Additionally, a Boyden chamber assay revealed that the TGF-beta1-induced increase in invasiveness of HSC-4 cells was significantly inhibited by MMP-10 small interfering RNA (siRNA). Intriguingly, Slug siRNA suppressed TGF-beta1-induced expression of MMP-10. These results suggest that TGF-beta1 induces invasion in HSC-4 cells through the upregulation of MMP-10 expression in a Slug-dependent manner. On the other hand, Slug siRNA suppressed TGF-beta1-induced Wnt-5b expression. Wnt-5b significantly induced MMP-10 expression, whereas Wnt-5b siRNA suppressed the TGF-beta1-induced increase in invasiveness, suggesting that TGF beta1-induced expression of MMP-10 and the resulting upregulation of invasiveness are mediated by Wnt-5b. Overall, these results suggest that TGF-beta1 stimulates HSC-4 cell invasion through the Slug/Wnt-5b/MMP-10 signalling axis. PMID- 26861995 TI - Microglia in central nervous system repair after injury. AB - Accumulating evidence suggests that immune cells perform crucial inflammation related functions including clearing dead tissue and promoting wound healing. Thus, they provide a conducive environment for better neuronal regeneration and functional recovery after adult mammalian central nervous system (CNS) injury. However, activated immune cells can also induce secondary damage of intact tissue and inhibit post-injury CNS repair. The inflammation response is due to the microglial production of cytokines and chemokines for the recruitment of peripheral immune cell populations, such as monocytes, neutrophils, dendritic cells and T lymphocytes. Interestingly, microglia and T lymphocytes can be detected at the injured site in both the early and later stages after nerve injury, whereas other peripheral immune cells infiltrate the injured parenchyma of the brain and spinal cord only in the early post-injury phase, and subsequently disappear. This suggests that microglia and T cells may play crucial roles in the post-injury functional recovery of the CNS. In this review, we summarize the current studies on microglia that examined neuronal regeneration and the molecular signalling mechanisms in the injured CNS. Better understanding of the effects of microglia on neural regeneration will aid the development of therapy strategies to enhance CNS functional recovery after injury. PMID- 26861997 TI - Modeling Macroinvertebrate Community Dynamics in Stream Mesocosms Contaminated with a Pesticide. AB - Modeling community dynamics of aquatic invertebrates is an important but challenging task, in particular in ecotoxicological risk assessment. Systematic parameter estimation and rigorous assessment of model uncertainty are often lacking in such applications. We applied the mechanistic food web model Streambugs to investigate the temporal development of the macroinvertebrate community in an ecotoxicological mesocosm experiment with pulsed contaminations with the insecticide thiacloprid. We used Bayesian inference to estimate parameters and their uncertainty. Approx. 85% of all experimental observations lie within the 90% uncertainty intervals indicating reasonably good fits of the calibrated model. However, a validation with independent data was not possible due to lacking data. Investigation of vital rates and limiting factors in the model yielded insights into recovery dynamics. Inclusion of the emergence process and sub-lethal effects turned out to be potentially relevant model extensions. Measurements of food source dynamics, individual body size (classes), and additional knowledge on sub-lethal effects would support more accurate modeling. This application of a process-based, ecotoxicological community model with uncertainty assessment by Bayesian inference increased our process understanding of toxicant effects in macroinvertebrate communities and helped identifying potential improvements in model structure and experimental design. PMID- 26861996 TI - Interaction of NOS1AP with the NOS-I PDZ domain: Implications for schizophrenia related alterations in dendritic morphology. AB - Schizophrenia involves morphological brain changes, including changes in synaptic plasticity and altered dendritic development. Amongst the most promising candidate molecules for schizophrenia are neuronal nitric oxide (NO) synthase (NOS-I, also known as nNOS) and its adapter protein NOS1AP (previously named CAPON). However, the precise molecular mechanisms by which NOS-I and NOS1AP affect disease pathology remain to be resolved. Interestingly, overexpression of NOS1AP affects dendritic morphology, possibly through increased association with the NOS-I PDZ domain. To investigate the effect of NOS1AP on dendritic morphology we overexpressed different NOS1AP isoforms, NOS1AP deletion mutants and the aminoterminal 133 amino acids of NOS-I (NOS-IN133) containing an extended PDZ domain. We examined the interaction of the overexpressed constructs with endogenous NOS-I by co-immunoprecipitation and the consequences of increased NOS I/NOS1AP PDZ interaction in primary cultures of hippocampal and cortical neurons from C57BL/6J mice. Neurons overexpressing NOS1AP isoforms or deletion mutants showed highly altered spine morphology and excessive growth of filopodia-like protrusions. Sholl analysis of immunostained primary cultured neurons revealed that dendritic branching was mildly affected by NOS1AP overexpression. Our results hint towards an involvement of NOS-I/NOS1AP interaction in the regulation of dendritic spine plasticity. As altered dendritic spine development and filopodial outgrowth are important neuropathological features of schizophrenia, our findings may provide insight into part of the molecular mechanisms involved in brain morphology alterations observed in schizophrenia. As the NOS-I/NOS1AP interface can be targeted by small molecules, our findings ultimately might help to develop novel treatment strategies for schizophrenia patients. PMID- 26861998 TI - A recombinant subunit vaccine for the control of ovine psoroptic mange (sheep scab). AB - Sheep scab, caused by infestation with the mite Psoroptes ovis, is highly contagious, causing intense pruritus and represents a major welfare and economic concern. Disease control strategies rely upon chemotherapy, however, sustainability is questionable due to issues of chemical residues, eco-toxicity and acaricide resistance. Control by vaccination is supported by demonstration of protective immunity in sheep previously infested with P. ovis. We identified vaccine candidates for P. ovis based on: (1) antigens selected by their interaction with host signalling pathways and the host immune-response; and (2) those shown to be either immunogenic or involved in mite feeding. This resulted in the development and validation, in repeated immunisation and challenge trials, of a seven recombinant protein sub-unit cocktail vaccine. Sheep were inoculated on three occasions, 2 weeks apart, along with QuilA adjuvant. Vaccination resulted in highly significant reductions in both lesion size (up to 63%) and mite numbers (up to 56%) following challenge. Mean lesion size in vaccinates was significantly smaller than controls from 1 week post infestation (wpi) until the end of the experiment at 6 wpi. All antigens elicited serum IgG responses following immunisation and prior to infestation, whereas controls did not produce antigen-specific IgG during the pre-infestation period. Vaccinated animals showed an amnestic response, with levels of antigen-specific IgG against muGST, Pso o 1 and Pso o 2 increasing following infestation. This vaccine represents the greatest reduction in lesion size to date with a sheep scab vaccine, providing encouragement for future production of a commercially-viable means of immunoprophylaxis. PMID- 26861999 TI - The anti-proliferative effect of cation channel blockers in T lymphocytes depends on the strength of mitogenic stimulation. AB - Ion channels are crucially important for the activation and proliferation of T lymphocytes, and thus, for the function of the immune system. Previous studies on the effects of channel blockers on T cell proliferation reported variable effectiveness due to differing experimental systems. Therefore our aim was to investigate how the strength of the mitogenic stimulation influences the efficiency of cation channel blockers in inhibiting activation, cytokine secretion and proliferation of T cells under standardized conditions. Human peripheral blood lymphocytes were activated via monoclonal antibodies targeting the TCR-CD3 complex and the co-stimulator CD28. We applied the blockers of Kv1.3 (Anuroctoxin), KCa3.1 (TRAM-34) and CRAC (2-Apb) channels of T cells either alone or in combination with rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR). Five days after the stimulation ELISA and flow cytometric measurements were performed to determine IL-10 and IFN-gamma secretion, cellular viability and proliferation. Our results showed that ion channel blockers and rapamycin inhibit IL-10 and IFN-gamma secretion and cell division in a dose dependent manner. Simultaneous application of the blockers for each channel along with rapamycin was the most effective, indicating synergy among the various activation pathways. Upon increasing the extent of mitogenic stimulation the anti proliferative effect of the ion channel blockers diminished. This phenomenon may be important in understanding the fine-tuning of T cell activation. PMID- 26862000 TI - Temporal dynamics of choice behavior in rats and humans: an examination of pre- and post-choice latencies. AB - Identifying similarities and differences in choice behavior across species is informative about how basic mechanisms give rise to more complex processes. In the present study, we compared pre- and post-choice latencies between rats and humans under two paradigms. In Experiment 1, we used a cued choice paradigm where subjects were presented with a cue that directed them as to which of two options to respond for rewards. In Experiment 2, subjects were free to choose between two options in order to procure rewards. In both Experiments rewards were delivered with distinct probabilities. The trial structure used in these experiments allowed the choice process to be decomposed into pre- and post-choice processes. Overall, post-choice latencies reflected the difference in reward probability between the two options, where latencies for the option with higher probability of reward were longer than those for the option with lower probability of reward. An interesting difference between rats and humans was observed: the choice behavior for humans, but not rats, was sensitive to the free-choice aspect of the tasks, such that in free-choice trials post-choice latencies no longer reflected the difference in reward probabilities between the two options. PMID- 26862001 TI - Comparative assessment of methods for the fusion transcripts detection from RNA Seq data. AB - RNA-Seq made possible the global identification of fusion transcripts, i.e. "chimeric RNAs". Even though various software packages have been developed to serve this purpose, they behave differently in different datasets provided by different developers. It is important for both users, and developers to have an unbiased assessment of the performance of existing fusion detection tools. Toward this goal, we compared the performance of 12 well-known fusion detection software packages. We evaluated the sensitivity, false discovery rate, computing time, and memory usage of these tools in four different datasets (positive, negative, mixed, and test). We conclude that some tools are better than others in terms of sensitivity, positive prediction value, time consumption and memory usage. We also observed small overlaps of the fusions detected by different tools in the real dataset (test dataset). This could be due to false discoveries by various tools, but could also be due to the reason that none of the tools are inclusive. We have found that the performance of the tools depends on the quality, read length, and number of reads of the RNA-Seq data. We recommend that users choose the proper tools for their purpose based on the properties of their RNA-Seq data. PMID- 26862002 TI - Excess Entropy Scaling Law for Diffusivity in Liquid Metals. AB - Understanding how dynamic properties depend on the structure and thermodynamics in liquids is a long-standing open problem in condensed matter physics. A very simple approach is based on the Dzugutov contribution developed on model fluids in which a universal (i.e. species-independent) connection relates the pair excess entropy of a liquid to its reduced diffusion coefficient. However its application to "real" liquids still remains uncertain due to the ability of a hard sphere (HS) reference fluid used in reducing parameters to describe complex interactions that occur in these liquids. Here we use ab initio molecular dynamics simulations to calculate both structural and dynamic properties at different temperatures for a wide series of liquid metals including Al, Au, Cu, Li, Ni, Ta, Ti, Zn as well as liquid Si and B. From this analysis, we demonstrate that the Dzugutov scheme can be applied successfully if a self-consistent method to determine the packing fraction of the hard sphere reference fluid is used as well as the Carnahan-Starling approach to express the excess entropy. PMID- 26862003 TI - Circadian variations in the liver metabolites of medaka (Oryzias latipes). AB - Circadian rhythms are biological rhythms with a period of around 24 hours. In this study, we compared the metabolome of the liver of medaka during the day and night. To comprehensively analyze the circadian variations in the levels of metabolites in the liver, livers were isolated from Zeitgeber time (ZT)4 and ZT16, and the variations in metabolite levels were evaluated. Inosinemonophosphate (IMP) and uridinemonophosphate (UMP) were found to be increased at night, indicating that nucleotide synthesis is most active during the night. Furthermore, the levels of metabolites of the tricarboxylic acid cycle were also reduced at night. In addition, the levels of many amino acids were reduced during the night, suggesting that the amino acids had been degraded. Moreover, the citrulline/ornithine ratio, which is related to arginine consumption, was lower during the day than at night. This pattern suggests that the urea cycle is activated during the day, whereas large amounts of nitric oxide and citrulline may be produced from arginine via nitric oxide synthase during the night. The results of this metabolomic analysis may be useful in future fundamental research to provide insight into chronobiology as well as applied research on drug evaluations using medaka as a model species. PMID- 26862004 TI - What is the safe upper intake level of folic acid for the nervous system? Implications for folic acid fortification policies. AB - Between 1945 and 1959 it was convincingly documented that folic acid can precipitate or aggravate the neurological and haematological consequences of vitamin B12 deficiency by increasing the demand for vitamin B12. Since then there has been much misunderstanding of the issues, mainly by advocates of folic acid fortification who have been inclined to minimise or even dismiss the risks by misinterpreting the evidence as only a 'masking' of the anaemia of pernicious anaemia. Recent studies in the era of fortification are rediscovering the risks to the nervous system, especially cognitive function, of excess folate in the presence of vitamin B12 deficiency. I have reviewed the Reports of four Expert Advisory Committees in Europe and the USA, which suggest that the safe upper tolerable limit (UL) for folic acid is 1 mg in adults. These reports are unsound and there is already evidence of neurological harm from long-term exposure to doses of folic acid between 0.5 and 1 mg in the presence of vitamin B12 deficiency. There is an urgent need to review the safe UL for folic acid and to consider the addition of vitamin B12 to folic acid fortification policies. PMID- 26862005 TI - Long-term association between dairy consumption and risk of childhood obesity: a systematic review and meta-analysis of prospective cohort studies. AB - BACKGROUND/OBJECTIVES: Data from small-scale, short-term, clinical trials suggest a beneficial effect of dairy consumption on the risk of childhood obesity; however, the long-term association is unclear. Therefore, we aim to examine the longitudinal association between dairy consumption and the risk of overweight/obesity in children and adolescents by conducting a systematic review and meta-analysis of prospective cohort studies. SUBJECTS/METHODS: Eligible studies were identified by searching PubMed and EMBASE through March 2015. Additional studies were retrieved via Google Scholar or a hand review of the reference lists from relevant articles. Pooled associations of interest were estimated by using a random-effects model. The heterogeneity for each pooled analysis was evaluated by I(2) statistic as well as by Cochran's Q test. Publication bias was assessed by using both Egger's and Begg's tests. RESULTS: Ten studies comprising 46,011 children and adolescents with an average 3-year follow-up were included. As compared with those who were in the lowest group of dairy consumption, children in the highest intake group were 38% less likely to have childhood overweight/obesity (pooled odds ratio (OR)=0.62; 95% confidence interval (CI): 0.49, 0.80). With each 1 serving/day increment in dairy consumption, the percentage of body fat was reduced by 0.65% (beta=0.65; 95% CI: 1.35, 0.06; P=0.07), and the risk of overweight/obesity was 13% lower (OR=0.87; 95% CI: 0.74, 0.98). CONCLUSIONS: Accumulated evidence from prospective cohort studies suggests that dairy consumption is inversely and longitudinally associated with the risk of childhood overweight/obesity. Further studies are warranted to examine the types of dairy products in relation to the risk of childhood overweight/obesity. PMID- 26862006 TI - Reliability of 24-h void frequency as an index of hydration status when euhydrated and hypohydrated. AB - BACKGROUND/OBJECTIVES: Void frequency (VF) is significantly correlated to hydration status, but it is unknown whether VF is reliable when an individual is repeatedly euhydrated (EU) or hypohydrated (HY). The purpose of this study was to test the reliability of VF when individuals were EU or HY on multiple occasions. SUBJECTS/METHODS: Fourteen males (age 22+/-2 years, mass 79.1+/-12.8 kg) completed three EU trials achieved with 24-h ad libitum fluid intake, and 14 males (age 22+/-2 years, mass 78.6+/-10.4 kg) completed three HY trials achieved with 24-h fluid restriction. Twenty-four hour urine was collected and analyzed for specific gravity (USG) and VF. Subjects voided at a 'normal urgency' (rated a '2' on a 0-4 perceptual scale) throughout each 24-h period. RESULTS: Twenty-four hour USG was greater and VF was lower when HY (1.026+/-0.003 and 5+/-2, respectively) versus EU (1.014+/-0.003 and 7+/-2; both P<0.05). Intra-class correlations for VF between the three trials at each hydration status were deemed acceptable (0.863 and 0.849 for EU and HY, respectively). Within-subject coefficients of variation for VF were 15+/-9 and 21+/-14% for the EU and HY trials. CONCLUSIONS: VF is a reliable index of 24-h hydration status when healthy young males are EU or HY and voiding at a consistent 'urgency'. PMID- 26862007 TI - Validation of an updated evidence-based protocol for proactive gastrostomy tube insertion in patients with head and neck cancer. AB - BACKGROUND/OBJECTIVES: Evidence-based practice guidelines are available to assist in the decision making for nutrition interventions in patients with head and neck cancer. Re-assessment of guideline recommendations is important with changing demographics, new treatment regimens, advancing radiotherapy techniques, such as helical intensity-modulated radiotherapy, and the emergence of new literature. The aim of this study was to validate the updated high-risk category definition in our local hospital protocol for the swallowing and nutrition management of patients with head and neck cancer to determine the ongoing predictive ability for identifying proactive gastrostomy requirement in a new cohort. SUBJECTS/METHODS: Patients attending a major tertiary hospital for head and neck cancer treatment from 2010 to 2011 were included (n=270). Data were collected on patient demographics (age and gender), clinical factors (tumour site, staging and treatment), nutrition outcome measures (weight, enteral feeding) and protocol adherence. Sensitivity and specificity were calculated and compared with the original validation study. RESULTS: Proactive gastrostomy tubes were inserted in 86 patients. Overall protocol adherence was 93%. Sensitivity improved to 72% (increase of 18%) and specificity improved to 96% (increase of 3%) compared with the original validation study where patients received three-dimensional (3-D) conformal radiotherapy. CONCLUSIONS: The results of this study confirm that the updated high-risk category in the protocol for the swallowing and nutrition management of patients with head and neck cancer remains valid to predict proactive gastrostomy in a mixed population receiving helical intensity-modulated radiotherapy and 3-D conformal radiotherapy. The protocol has an improved sensitivity and specificity and hence remains just as relevant for advanced techniques of radiation treatment delivery. PMID- 26862008 TI - Effect of meal frequency on glucose and insulin levels in women with polycystic ovary syndrome: a randomised trial. AB - BACKGROUND/OBJECTIVES: The aim of the study was to compare the effect of two-meal patterns (three vs six meals per day) on glucose and insulin levels in women with polycystic ovary syndrome (PCOS). SUBJECTS/METHODS: In a randomised, crossover, 24-week study, 40 women with PCOS, aged 27+/-6 years, body mass index 27+/-6 kg/m(2), followed a weight maintenance diet (% carbohydrates:protein:fat, 40:25:35), consumed either as a three- or a six-meal pattern, with each intervention lasting for 12 weeks. Anthropometric measurements, diet compliance and subjective hunger, satiety and desire to eat were assessed biweekly. All women underwent an oral glucose tolerance test (OGTT) with 75 g glucose for measurement of plasma glucose and insulin at the beginning and end of each intervention. HaemoglobinA1c (HbA1c), blood lipids and hepatic enzymes were measured at the beginning and end of each intervention. RESULTS: Body weight remained stable throughout the study. Six meals decreased significantly fasting insulin (P=0.014) and post-OGTT insulin sensitivity (Matsuda index, P=0.039) vs three meals. After incorporation of individual changes over time, with adjustment for potential confounders, the only variable that remained significant was the Matsuda index, which was then used in multivariate analysis and general linear models. Six meals improved post-OGTT insulin sensitivity independently of age and body weight vs three meals (P=0.012). No significant differences were found between six and three meals for glucose, HbA1c, blood lipids, hepatic enzymes, subjective desire to eat and satiety. CONCLUSIONS: Six meals had a more favourable effect on post-OGTT insulin sensitivity in women with PCOS compared with isocaloric three meals. PMID- 26862011 TI - Cadmium sulfide/graphitic carbon nitride heterostructure nanowire loading with a nickel hydroxide cocatalyst for highly efficient photocatalytic hydrogen production in water under visible light. AB - Photocatalytic hydrogen production from water in a noble-metal-free system has attracted much attention in recent years. Herein we report on the use of core/shell cadmium sulfide/graphitic carbon nitride (CdS/g-C3N4) heterojunction nanorods modified by nickel hydroxide (Ni(OH)2) as a highly efficient photocatalyst for visible light-driven hydrogen production from water. Due to efficient separation of the photoexcited charge carriers in the CdS/g-C3N4 core/shell nanorods and the synergistic effect of Ni(OH)2, the optimal hydrogen evolution rate over Ni(OH)2-CdS/g-C3N4 is 115.18 MUmol h(-1) mg(-1) under visible light irradiation (lambda > 420 nm), which is ~26 times higher than the CdS/g C3N4 nanorod composite without Ni(OH)2 and ~7 times better than the 0.5 wt% Pt CdS/g-C3N4 nanorod composite. The apparent quantum efficiency is ~16.7% at an excitation of 450 nm. During photocatalysis, no degradation of Ni(OH)2 was observed based on the XPS data, indicating that it is a robust cocatalyst. Moreover, the present photocatalyst showed excellent photocatalytic stability for hydrogen production and the turnover number (TON) reached ~24,600 over 90 hours. PMID- 26862010 TI - Structure-Property-Function Relationship in Humic Substances to Explain the Biological Activity in Plants. AB - Knowledge of the structure-property-function relationship of humic substances (HSs) is key for understanding their role in soil. Despite progress, studies on this topic are still under discussion. We analyzed 37 humic fractions with respect to their isotopic composition, structural characteristics, and properties responsible for stimulating plant root parameters. We showed that regardless of the source of origin of the carbon (C3 or C4), soil-extracted HSs and humic acids (HAs) are structurally similar to each other. The more labile and functionalized HS fraction is responsible for root emission, whereas the more recalcitrant and less functionalized HA fraction is related to root growth. Labile structures promote root stimulation at lower concentrations, while recalcitrant structures require higher concentrations to promote a similar stimulus. These findings show that lability and recalcitrance, which are derived properties of humic fractions, are related to the type and intensity of their bioactivity. In summary, the comparison of humic fractions allowed a better understanding of the relationship between the source of origin of plant carbon and the structure, properties, and type and intensity of the bioactivity of HSs in plants. In this study, scientific concepts are unified and the basis for the agronomic use of HSs is established. PMID- 26862012 TI - Corrigendum: A draft network of ligand-receptor-mediated multicellular signalling in human. PMID- 26862009 TI - Impact of UGT1A1 genotype upon toxicities of combination with low-dose irinotecan plus platinum. AB - AIM: Irinotecan-induced severe toxicities are possibly related to UGT1A1*6 and *28 genotypes. However, the correlation between UGT1A1 polymorphisms and the risk of toxicities induced by low-dose irinotecan plus platinum combination therapy still remains controversial. This prospective observational study aimed to examine the correlation between UGT1A1 genotypes and clinical outcomes of low dose irinotecan (median 60 mg/m(2) , range 25-115 mg/m(2) ) plus platinum in Japanese patients with solid tumors. METHODS: Toxicity profiles were compared between UGT1A1 SNP heterozygotes (hetero-group) and patients with homozygous SNP profile (*6/*6, *28/*28 and *6/*28). Logistic regression models were used to identify independent risk factors for these toxicities. RESULTS: A total of 331 patients were enrolled: 84% with hetero-group and 16% with homo-group. Although the initial irinotecan dose was similar, the dose intensities during the three cycles were significantly lower in the homo-group (P < 0.01). Grade 3/4 hematological toxicities were significantly more frequent in the homo-group. Multivariable analysis identified UGT1A1 genotype (P < 0.01) as an independent factor for grade 4 hematological toxicity in the first treatment cycle. CONCLUSION: UGT1A1 genotype has a major impact on the increased risk of severe hematological toxicities, even in low-dose irinotecan regimens. UGT1A1 genotypes are useful biomarkers for predicting severe hematological toxicities in patients treated with irinotecan plus platinum analog. PMID- 26862013 TI - Heart valve regeneration: the need for systems approaches. AB - Tissue-engineered heart valves are promising alternatives to address the limitations of current valve replacements, particularly for growing children. Current heart valve tissue engineering strategies involve the selection of biomaterial scaffolds, cell types, and often in vitro culture conditions aimed at regenerating a valve for implantation and subsequent maturation in vivo. However, identifying optimal combinations of cell sources, biomaterials, and/or bioreactor conditions to produce functional, durable valve tissue remains a challenge. Despite some short-term success in animal models, attempts to recapitulate aspects of the native heart valve environment based on 'best guesses' of a limited number of regulatory factors have not proven effective. Better outcomes for valve tissue regeneration will likely require a systems-level understanding of the relationships between multiple interacting regulatory factors and their effects on cell function and tissue formation. Until recently, conventional culture methods have not allowed for multiple design parameters to be considered at once. Emerging microtechnologies are well suited to systematically probe multiple inputs, in combination, in high throughput and with great precision. When combined with statistical and network systems analyses, these microtechnologies have excellent potential to define multivariate signal-response relationships and reveal key regulatory pathways for robust functional tissue regeneration. PMID- 26862014 TI - Prepared to practice? Perception of career preparation and guidance of recent medical graduates at two campuses of a transnational medical school: a cross sectional study. AB - BACKGROUND: Graduating medical students enter the workforce with substantial medical knowledge and experience, yet little is known about how well they are prepared for the transition to medical practice in diverse settings. We set out to compare perceptions of medical school graduates' career guidance with their perceptions of preparedness to practice as interns. We also set out to compare perceptions of preparedness for hospital practice between graduates from two transnational medical schools. METHODS: This was a cross-sectional study. A Preparedness for Hospital Practice (PHPQ) survey and career guidance questionnaire was sent to recent medical graduates, incorporating additional free text responses on career preparation. Data was analyzed using descriptive statistics and tests of association including Chi-square, Mann-Whitney U and Kruskal-Wallis H tests. RESULTS: Forty three percent (240/555) of graduates responded to the survey: 39 % of respondents were domestic (Dublin, Ireland or Manama, Kingdom of Bahrain) and interning locally; 15 % were overseas students interning locally; 42 % were overseas students interning internationally and 4 % had not started internship. Two variables explained 13 % of the variation in preparedness for hospital practice score: having planned postgraduate education prior to entering medical school and having helpful career guidance in medical school. Overseas graduates interning internationally were more likely to have planned their postgraduate career path prior to entering medical school. Dublin graduates found their career guidance more helpful than Bahrain counterparts. The most cited shortcomings were lack of structured career advice and lack of advice on the Irish and Bahraini postgraduate systems. CONCLUSIONS: This study has demonstrated that early consideration of postgraduate career preparation and helpful medical school career guidance has a strong association with perceptions of preparedness of medical graduates for hospital practice. In an era of increasing globalization of medical education, these findings can direct ongoing efforts to ensure all medical students receive career guidance and preparation for internship appropriate to their destination. PMID- 26862016 TI - Antithrombin III for critically ill patients: a systematic review with meta analysis and trial sequential analysis. AB - PURPOSE: Antithrombin III (AT III) is an anticoagulant with anti-inflammatory properties. We assessed the benefits and harms of AT III in critically ill patients. METHODS: We searched from inception to 27 August 2015 in CENTRAL, MEDLINE, EMBASE, CAB, BIOSIS and CINAHL. We included randomized controlled trials (RCTs) irrespective of publication status, date of publication, blinding status, outcomes published or language. RESULTS: We included 30 RCTs with a total of 3933 participants. The majority of included trials were at high risk of bias. Combining all trials, regardless of bias, showed no statistically significant effect of AT III on mortality (RR 0.95, 95% CI 0.88-1.03, I (2) = 0%, fixed effect model, 29 trials, 3882 participants). Among those with severe sepsis and disseminated intravascular coagulation (DIC), AT III showed no impact on mortality (RR 0.95, 95% Cl 0.88-1.03, I (2) = 0%, fixed-effect model, 12 trials, 2858 participants). We carried out multiple subgroup and sensitivity analyses to assess the benefits and harms of AT III and to examine the impact of risk of bias. AT III significantly increased bleeding events (RR 1.58, 95% CI 1.35-1.84, I (2) = 0%, fixed-effect model, 11 trials, 3019 participants). However, for all other outcome measures and analyses, the results did not reach statistical significance. CONCLUSIONS: There is insufficient evidence to support AT III substitution in any category of critically ill participants including those with sepsis and DIC. AT III did not show an impact on mortality, but increased the risk of bleeding. PMID- 26862015 TI - Steroid 17-hydroxylase and 17,20-lyase deficiencies, genetic and pharmacologic. AB - Steroid 17-hydroxylase 17,20-lyase (cytochrome P450c17, P450 17A1, CYP17A1) catalyzes two major reactions: steroid 17-hydroxylation followed by the 17,20 lyase reactions. The most severe mutations in the cognate CYP17A1 gene abrogate all activities and cause combined 17-hydroxylase/17,20-lyase deficiency (17OHD), a biochemical phenotype that is replicated by treatment with the potent CYP17A1 inhibitor abiraterone acetate. The adrenals of patients with 17OHD synthesize 11 deoxycorticosterone (DOC) and corticosterone but no 19-carbon steroids, similar to the rodent adrenal, and DOC causes hypertension and hypokalemia. Loss of 17,20 lyase activity precludes sex steroid synthesis and leads to sexual infantilism. Rare missense CYP17A1 mutations minimally disrupt 17-hydroxylase activity but cause isolated 17,20-lyase deficiency (ILD), Mutations in the POR gene encoding the required cofactor protein cytochrome P450-oxidoreductase causes a spectrum of disease from ILD to 17OHD combined with 21-hydroxylase and aromatase deficiencies, sometimes including skeletal malformations. Mutations in the CYB5A gene encoding a second cofactor protein cytochrome b5 also selectively disrupt 17,20-lyase activity and cause the purest form of ILD. The clinical manifestations of these conditions are best understood in the context of the biochemistry of CYP17A1. PMID- 26862017 TI - Focus on infection and sepsis in intensive care patients. PMID- 26862019 TI - Partial extracorporeal lung support in acute respiratory distress syndrome: preliminary experience in a second level hospital. PMID- 26862018 TI - Effect of ICU strain on timing of limitations in life-sustaining therapy and on death. AB - PURPOSE: The effect of capacity strain in an ICU on the timing of end-of-life decision-making is unknown. We sought to determine how changes in strain impact timing of new do-not-resuscitate (DNR) orders and of death. METHODS: Retrospective cohort study of 9891 patients dying in the hospital following an ICU stay >=72 h in Project IMPACT, 2001-2008. We examined the effect of ICU capacity strain (measured by standardized census, proportion of new admissions, and average patient acuity) on time to initiation of DNR orders and time to death for all ICU decedents using fixed-effects linear regression. RESULTS: Increases in strain were associated with shorter time to DNR for patients with limitations in therapy (predicted time to DNR 6.11 days for highest versus 7.70 days for lowest quintile of acuity, p = 0.02; 6.50 days for highest versus 7.77 days for lowest quintile of admissions, p < 0.001), and shorter time to death (predicted time to death 7.64 days for highest versus 9.05 days for lowest quintile of admissions, p < 0.001; 8.28 days for highest versus 9.06 days for lowest quintile of census, only in closed ICUs, p = 0.006). Time to DNR order significantly mediated relationships between acuity and admissions and time to death, explaining the entire effect of acuity, and 65 % of the effect of admissions. There was no association between strain and time to death for decedents without a limitation in therapy. CONCLUSIONS: Strains in ICU capacity are associated with end-of-life decision-making, with shorter times to placement of DNR orders and death for patients admitted during high-strain days. PMID- 26862020 TI - Theoretical characterisation of point defects on a MoS2 monolayer by scanning tunnelling microscopy. AB - Different S and Mo vacancies as well as their corresponding antisite defects in a free-standing MoS2 monolayer are analysed by means of scanning tunnelling microscopy (STM) simulations. Our theoretical methodology, based on the Keldysh nonequilibrium Green function formalism within the density functional theory (DFT) approach, is applied to simulate STM images for different voltages and tip heights. Combining the geometrical and electronic effects, all features of the different STM images can be explained, providing a valuable guide for future experiments. Our results confirm previous reports on S atom imaging, but also reveal a strong dependence on the applied bias for vacancies and antisite defects that include extra S atoms. By contrast, when additional Mo atoms cover the S vacancies, the MoS2 gap vanishes and a bias-independent bright protrusion is obtained in the STM image. Finally, we show that the inclusion of these point defects promotes the emergence of reactive dangling bonds that may act as efficient adsorption sites for external adsorbates. PMID- 26862021 TI - Biomechanical properties of breast tissue, a state-of-the-art review. AB - This paper reviews the existing literature on the tests used to determine the mechanical properties of women breast tissues (fat, glandular and tumour tissue) as well as the different values of these properties. The knowledge of the mechanical properties of breast tissue is important for cancer detection, study and planning of surgical procedures such as surgical breast reconstruction using pre-surgical methods and improving the interpretation of clinical tests. Based on the data collected from the analysed studies, some important conclusions were achieved: (1) the Young's modulus of breast tissues is highly dependent on the tissue preload compression level, and (2) the results of these studies clearly indicate a wide variation in moduli not only among different types of tissue but also within each type of tissue. These differences were most evident in normal fat and fibroglandular tissues. PMID- 26862022 TI - Hyalinizing Clear Cell Carcinoma with Biopsy-Proven Spinal Metastasis: Case Report and Review of Literature. AB - BACKGROUND: Hyalinizing clear cell carcinoma (HCCC) is a rare epithelial malignant neoplasm typically arising from the minor salivary glands. Although it has been described as a benign neoplasm, there are increasing reports of malignant features and metastases to the lungs; we present the first case of biopsy-proven spinal metastases from HCCC and an overview of the literature. CASE DESCRIPTION: This is a single-patient case report in which we used immunohistochemistry and fluorescence in situ hybridization for Ewing sarcoma breakpoint region 1 translocation to confirm the diagnosis of HCCC in a spinal metastasis. The diagnosis of metastatic HCCC was confirmed on the basis of histopathology, immunohistochemistry, and fluorescence in situ hybridization studies. CONCLUSIONS: We present the first pathologically confirmed case of a spinal metastasis in HCCC. As increasing of metastatic HCCC arise, a reconsideration of HCCC as a potentially high-grade disease seems increasingly necessary as it may impact the current treatment paradigm. PMID- 26862023 TI - Primary Intracranial Alveolar Soft-Part Sarcoma: Report of Two Cases and a Review of the Literature. AB - BACKGROUND: Alveolar soft part sarcoma (ASPS), a rare malignant soft-tissue sarcoma affecting mainly adolescents and young children, frequently metastasizes to the brain. Primary intracranial ASPS, however, is extremely rare. We present 2 cases of primary intracranial ASPS without demonstrable systemic lesions. CASE PRESENTATION: We report 2 cases of primary intracranial lesions that were surgically treated, and a postoperative diagnosis of ASPS was determined in both of the cases. The tumor in the 28-year-old female patient completely resolved after a treatment course consisting of surgical intervention and radiotherapy. After a follow-up period of 27 months, the patient was tumor-free. The other patient was a 13-year-old boy with a right middle cranial fossa tumor who experienced subtotal surgery, experienced a tumor relapse, and died 2 years after surgery. CONCLUSIONS: This is the fifth report about primary intracranial ASPS. We herein present the clinical pathologic characteristics, imaging features, and differential diagnosis of primary ASPS of the brain. Gross total resection is the most effective therapeutic option for primary intracranial ASPS. PMID- 26862024 TI - Academic Output and Social Media: A Marriage of Opposites. PMID- 26862025 TI - Magnetic Resonance Imaging-Based Assessment of Gadolinium-Conjugated Diethylenetriamine Penta-Acetic Acid Test-Infusion in Detecting Dysfunction of Convection-Enhanced Delivery Catheters. AB - BACKGROUND: In a phase 1 trial conducted at our institute, convection-enhanced delivery (CED) was used to administrate the Delta-24-RGD adenovirus in patients with a recurrent glioblastoma multiforme. Infusion of the virus was preceded by a gadolinium-conjugated diethylenetriamine penta-acetic acid (Gd-DTPA) test infusion. In the present study, we analyzed the results of Gd-DTPA test infusion through 50 catheters. METHODS: Thirteen adults with a recurrent glioblastoma multiforme were enrolled in a larger phase 1 multicenter, dose-finding study, in which a conditionally replication-competent adenovirus was administered by CED. Up to 4 infusion catheters per patient were placed intra- and/or peritumorally. Before infusion of the virus, a Gd-DTPA infusion was performed for 6 hours, directly followed by a MRI scan. The MRIs were evaluated for catheter position, Gd-DTPA distribution outcome, and contrast leakage. RESULTS: Leakage of Gd-DTPA into the cerebrospinal fluid was detected in 17 of the 50 catheters (34%). Sulcus crossing was the most frequent cause of leakage. In 8 cases, leakage could only be detected on the fluid-attenuated inversion recovery sequence. Nonleaking catheters showed a significantly larger Gd-DTPA distribution fraction (volume of distribution/volume of infusion) than leaking catheters (P = 0.009). A significantly lower volume of distribution/volume of infusion was observed in intratumoral catheters, compared with peritumoral catheters (P = 0.004). Gd-DTPA test infusion did not result in significant changes in Karnofsky Performance Score and Neurological Status. CONCLUSIONS: Pre-CED treatment infusion of Gd-DTPA is an adequate and safe method to identify dysfunctional catheters. The use of an optimized drug delivery catheter is necessary to reduce leakage and improve the efficacy of intracerebral drug infusion. PMID- 26862026 TI - How Does In Vivo Biliary Elimination of Drugs Change with Age? Evidence from In Vitro and Clinical Data Using a Systems Pharmacology Approach. AB - Information on the developmental changes in biliary excretion (BE) of drugs is sparse. The aims of this study were to collate literature data on the pharmacokinetics of biliary excretion of drugs used in pediatrics and to apply a physiologically based pharmacokinetic (PBPK) model to predict their systemic clearance (CL) with a view to elucidating age-related changes in biliary excretion. Drug parameters for azithromycin, ceftriaxone, and digoxin administered intravenously and buprenorphine (intravenous and sublingual) were collated from the literature and used in the Simcyp Simulator to predict adult CL values, which were then validated against observed data. The change in CL with age was simulated in the pediatric model and compared with observed data; where necessary, the ontogeny function associated with BE was applied to recover the age-related CL. For azithromycin a fraction of adult BE activity of 15% was necessary to predict the CL in neonates (26 weeks gestational age) and 100% activity was apparent by 7 months. For ceftriaxone and digoxin full BE activity appeared to be present at term birth; for digoxin, an adult BE activity of 10% was needed to predict the CL in premature neonates (30 weeks gestational age). The CL of buprenorphine with age was described by the ontogeny of the major elimination pathways (CYP3A4 and UGT1A1) with no ontogeny assumed for the biliary component. Thus, the ontogeny of BE for all four drugs appears to be rapid and they attain adult levels at birth or within the first few months of postnatal age. PMID- 26862027 TI - Endoscopic treatment for esophageal varices complicated by Isaacs' syndrome involving difficulty with conventional sedation. AB - A 54-year-old male consulted a local doctor with a chief complaint of systemic convulsions and muscle stiffness and was diagnosed with Isaacs' syndrome based on positive findings for antibodies against voltage-gated potassium channels in 2009. He subsequently experienced repeated hematemesis in 2013, at which time he was taken to our hospital by ambulance. Emergent endoscopy revealed esophageal varices with spurting bleeding. The bleeding was stopped with urgent endoscopic variceal ligation. Three days later, the patient developed sudden dyspnea with stridor during inspiration under sedation with an intravenous injection of low dose flunitrazepam prior to receiving additional treatment and was aroused with intravenous flumazenil, after which his dyspnea immediately improved. Dyspnea may be induced by muscle cramps associated with Isaacs' syndrome exacerbated by sedation. Endoscopic variceal ligation was performed safely using multiple ligation devices in an awake state following pre-medication with hydroxyzine, without sudden dyspnea. Endoscopists should be cautious of the use of sedatives in patients with diseases associated with muscle twitching or stiffness, as in the current case. In addition, it is necessary to administer endoscopic treatment in an awake state or under conscious sedation in patients with a high risk of dyspnea. PMID- 26862028 TI - Gestational Diabetes Testing: Making Sense of the Controversy. AB - Evidence has demonstrated that even mild increases in maternal blood sugar are associated with worsening pregnancy outcomes, particularly macrosomia, and that reducing blood sugar improves outcomes. Euglycemia can often be achieved with dietary modification and exercise without a need for medication. Despite this evidence, there continues to be controversy over exactly who, when, and how to test for gestational diabetes mellitus (GDM), with various professional organizations and experts in the field suggesting different strategies or not making specific recommendations at all. Potential sources of this controversy may include differences in opinion about the clinical importance of the consequences of GDM and the benefits of available interventions. Further, dichotomously diagnosing disease when the disease-defining characteristic is linear requires drawing a somewhat arbitrary line in the sand for diagnosis, which is likely to fall in a different place for different providers. Finally, given the resources and effort needed by both women and providers to address GDM, the availability of resources is likely to impact providers' perspectives on the ideal testing strategy. Given the differences among patient characteristics and available resources that exist in different health care settings, identifying one best strategy for GDM testing is not necessarily appropriate. However, given the potential benefits of identifying pregnant women with hyperglycemia, providers should use the most sensitive testing strategy that their patient population and resources allow. PMID- 26862029 TI - Erratum to: Response to Deep Brain Stimulation in the Lateral Hypothalamic Area in a Rat Model of Obesity: In Vivo Assessment of Brain Glucose Metabolism. PMID- 26862031 TI - Abnormal myocardial scintigraphy in a GTP cyclohydrolase 1 mutation carrier with Parkinson's disease. PMID- 26862030 TI - Prognostic factors for cerebral palsy and motor impairment in children born very preterm or very low birthweight: a systematic review. AB - AIM: There is a large literature reporting risk factor analyses for poor neurodevelopment in children born very preterm (VPT: <=32wks) or very low birthweight (VLBW: <=1250g), which to date has not been formally summarized. The aim of this paper was to identify prognostic factors for cerebral palsy (CP) and motor impairment in children born VPT/VLBW. METHOD: A systematic review was conducted using Medline, Embase, and Pyscinfo databases to identify studies published between 1 January 1990 and 1 June 2014 reporting multivariable prediction models for poor neurodevelopment in VPT/VLBW children (registration number CRD42014006943). Twenty-eight studies for motor outcomes were identified. RESULTS: There was strong evidence that intraventricular haemorrhage and periventricular leukomalacia, and some evidence that the use of postnatal steroids and non-use of antenatal steroids, were prognostic factors for CP. Male sex and gestational age were of limited use as prognostic factors for CP in cohorts restricted to <=32 weeks gestation; however, in children older than 5 years with no major disability, there was evidence that male sex was a predictive factor for motor impairment. INTERPRETATION: This review has identified factors which may be of prognostic value for CP and motor impairment in VPT/VLBW children and will help to form the basis of future prognostic research. PMID- 26862032 TI - Effect of ferrous chloride on biogas production and enzymatic activities during anaerobic fermentation of cow dung and Phragmites straw. AB - The effect of ferrous (added as FeCl2) on the anaerobic co-digestion of Phragmites straw and cow dung was studied by investigating the biogas properties, pH values, organic matter degradation (COD) and enzyme activities (cellulase, protease and dehydrogenase) at different stages of mesophilic fermentation. The results showed that Fe(2+) addition increased the cumulative biogas yields by 18.1 % by extending the peak period with high daily biogas yields. Meanwhile, the methane (CH4) contents in the Fe(2+) added groups were generally higher than the control group before the 15th day. The pH values were not significantly impacted by Fe(2+) concentrations during the fermentation process. The COD concentrations, cellulase, protease and dehydrogenase activities varied with the added Fe(2+) concentrations and the stages of the fermentation process. At the beginning stage of fermentation (4th day), Fe(2+) addition increased the biogas production by improving the cellulase and dehydrogenase activities which caused a decline in COD. At the peak stage of fermentation (8th day), Fe(2+) addition enhanced the cellulase and protease activities, and resulted in lower COD contents than the control group. When the biogas yields decreased again (13th day), the COD contents varied similar with the protease and dehydrogenase activities, whilst cellulase activities were not sensitive to Fe(2+) concentrations. At the end of fermentation (26th day), Fe(2+) addition decreased the cellulase activities, led to lower COD contents and finally resulted the lower biogas yields than the control group. Taking the whole fermentation process into account, the promoting effect of Fe(2+) addition on biogas yields was mainly attributed to the extension of the gas production peak stage and the improvement of cellulase activities. PMID- 26862033 TI - A multi-drug resistant Salmonella Typhimurium ST213 human-invasive strain (33676) containing the bla CMY-2 gene on an IncF plasmid is attenuated for virulence in BALB/c mice. AB - BACKGROUND: Classical strains of Salmonella enterica serovar Typhimurium (Typhimurium) predominantly cause a self-limiting diarrheal illness in humans and a systemic disease in mice. In this study, we report the characterization of a strain isolated from a blood-culture taken from a 15-year old woman suffering from invasive severe salmonellosis, refractory to conventional therapy with extended-spectrum cephalosporin (ESC). RESULTS: The strain, named 33676, was characterized as multidrug-resistant Salmonella serogroup A by biochemical, antimicrobial and serological tests. Multilocus sequence typing (MLST) and XbaI macrorestrictions (PFGE) showed that strain 33676 belonged to the Typhimurium ST213 genotype, previously described for other Mexican Typhimurium strains. PCR analyses revealed the presence of IncA/C, IncFIIA and ColE1-like plasmids and the absence of the Salmonella virulence plasmid (pSTV). Conjugation assays showed that the ESC-resistance gene bla CMY-2 was carried on the conjugative IncF plasmid, instead of the IncA/C plasmid, as found in previously studied ST213 strains. Although the IncA/C plasmid conferred most of the observed antimicrobial resistances it was not self-conjugative; it was rather able to conjugate by co integrating with the IncF plasmid. Strain 33676 was fully attenuated for virulence in BALB/c mice infections. Both type-three secretion system (T3SS), encoded in Salmonella pathogenicity islands 1 and 2 (SPI-1 and SPI-2), were functional in the 33676 strain and, interestingly, this strain produced the H2 FljB flagellin instead of the H1 FliC flagellin commonly expressed by S. enterica strains. CONCLUSIONS: Strain 33676 showed two main features that differentiate it from the originally described ST213 strains: 1) the bla CMY-2 gene was not carried on the IncA/C plasmid, but on a conjugative IncF plasmid, which may open a new route of dissemination for this ESC-resistance gene, and 2) it expresses the H2 FljB flagella, in contrast with the other ST213 and most Typhimurium reference strains. To our knowledge this is the first report of an IncF bla CMY-2 carrying plasmid in Salmonella. PMID- 26862034 TI - Statistical analysis and handling of missing data in cluster randomized trials: a systematic review. AB - BACKGROUND: Cluster randomized trials (CRTs) randomize participants in groups, rather than as individuals and are key tools used to assess interventions in health research where treatment contamination is likely or if individual randomization is not feasible. Two potential major pitfalls exist regarding CRTs, namely handling missing data and not accounting for clustering in the primary analysis. The aim of this review was to evaluate approaches for handling missing data and statistical analysis with respect to the primary outcome in CRTs. METHODS: We systematically searched for CRTs published between August 2013 and July 2014 using PubMed, Web of Science, and PsycINFO. For each trial, two independent reviewers assessed the extent of the missing data and method(s) used for handling missing data in the primary and sensitivity analyses. We evaluated the primary analysis and determined whether it was at the cluster or individual level. RESULTS: Of the 86 included CRTs, 80 (93%) trials reported some missing outcome data. Of those reporting missing data, the median percent of individuals with a missing outcome was 19% (range 0.5 to 90%). The most common way to handle missing data in the primary analysis was complete case analysis (44, 55%), whereas 18 (22%) used mixed models, six (8%) used single imputation, four (5%) used unweighted generalized estimating equations, and two (2%) used multiple imputation. Fourteen (16%) trials reported a sensitivity analysis for missing data, but most assumed the same missing data mechanism as in the primary analysis. Overall, 67 (78%) trials accounted for clustering in the primary analysis. CONCLUSIONS: High rates of missing outcome data are present in the majority of CRTs, yet handling missing data in practice remains suboptimal. Researchers and applied statisticians should carry out appropriate missing data methods, which are valid under plausible assumptions in order to increase statistical power in trials and reduce the possibility of bias. Sensitivity analysis should be performed, with weakened assumptions regarding the missing data mechanism to explore the robustness of results reported in the primary analysis. PMID- 26862036 TI - Evolution of the levels of human leukocyte antigen G (HLA-G) in Beninese infant during the first year of life in a malaria endemic area: using latent class analysis. AB - BACKGROUND: HLA-G, a non-classical HLA class I antigen, is of crucial interest during pregnancy by inhibiting maternal immune response. Its role during infections is discussed, and it has been described that high levels of soluble HLA-G during childhood increase the risk of malaria. To explore more precisely interactions between soluble HLA-G and malaria, latent class analysis was used to test whether distinct sub-populations of children, each with distinctive soluble HLA-G evolutions may suggest the existence of groups presenting variable malaria susceptibility. METHOD: A study was conducted in Benin from 2010 to 2013 and 165 children were followed from birth to 12 months. Evolution of soluble HLA-G was studied by the latent class method. RESULTS: Three groups of children were identified: one with consistently low levels of soluble HLA-G during follow-up, a second with very high levels and a last intermediate group. In all groups, low birth weight, high number of malaria infections and high exposure to malaria transmission were associated with high level of soluble HLA-G. Placental malaria was not. Presence of soluble HLA-G in cord blood increased the probability of belonging to the highest trajectory. CONCLUSION: These results, together with previous ones, confirm the important role of HLA-G in the individual susceptibility to malaria. Assaying soluble HLA-G at birth could be a good indicator of newborns more fragile and at risk of infections during childhood. PMID- 26862035 TI - Cilostazol suppresses angiotensin II-induced apoptosis in endothelial cells. AB - Patients with essential hypertension undergo endothelial dysfunction, particularly in the conduit arteries. Cilostazol, a type III phosphodiesterase inhibitor, serves a role in the inhibition of platelet aggregation and it is widely used in the treatment of peripheral vascular diseases. Previous studies have suggested that cilostazol suppresses endothelial dysfunction; however, it remains unknown whether cilostazol protects the endothelial function in essential hypertension. The aim of the present study was to investigate whether, and how, cilostazol suppresses angiotensin II (angII)-induced endothelial dysfunction. Human umbilical vein endothelial cells (HUVECs) and Sprague Dawley rats were exposed to angII and treated with cilostazol. Endothelial cell apoptosis and function, nitric oxide and superoxide production, phosphorylation (p) of Akt, and caspase-3 protein expression levels were investigated. AngII exposure resulted in the apoptosis of endothelial cells in vitro and in vivo. In vitro, cilostazol significantly suppressed the angII-induced apoptosis of HUVECs; however, this effect was reduced in the presence of LY294002, a phosphoinositide 3 kinase (PI3K) inhibitor. Furthermore, cilostazol suppressed the angII-induced p-Akt downregulation and cleaved caspase-3 upregulation. These effects were also alleviated by LY294002. In vivo, cilostazol suppressed the angII-induced endothelial cell apoptosis and dysfunction. Cilostazol was also demonstrated to partially reduced the angII-induced increase in superoxide production. The results of the present study suggested that cilostazol suppresses endothelial apoptosis and dysfunction by modulating the PI3K/Akt pathway. PMID- 26862038 TI - Experiences and perspectives of patients with post-polio syndrome and therapists with exercise and cognitive behavioural therapy. AB - BACKGROUND: Many persons affected with poliomyelitis develop post-polio syndrome (PPS) later in their life. Recently, the effectiveness of Exercise Therapy (ET) and Cognitive Behavioural Therapy (CBT) for PPS has been evaluated in a randomized controlled trial, but did not show a decrease in fatigue or improvement in secondary endpoints like Quality of Life and self-perceived activity limitations. The aim of this explorative study was to gain insight in the perceived effects and experiences of the interventions from the perspectives of the patients and therapists. METHODS: Qualitative data were collected through semi-structured interviews with 17 patients and 7 therapists. All participants were involved in the trial. A thematic analysis of the data was performed. RESULTS: Some patients experienced a short term enhanced endurance and a better use of energy during the day. However, in general patients did not experience a long lasting reduction of fatigue from the CBT or ET. Mainly patients of the CBT, but also some patients of the ET described an increase of self-esteem and self acceptance. As a result, patients were sometimes better able to perform physical activities during the day. In contrast to the CBT, the ET was in general perceived by the patients as an intensive therapy, which was difficult to fit into their daily routine. Therapists of both the CBT and the ET struggled with a low intrinsic motivation of the patients in the study. This made it sometimes difficult for the therapists to follow the protocol. CONCLUSION: Confirming the negative quantitative study outcome, the qualitative results did not demonstrate lasting effects on fatigue. Patients did, however, experience some benefits on self-esteem and acceptance of the disease. This study showed that it is of great importance to work with feasible interventions; they should fit the patients' needs on a practical (fit into their daily routine) and mental (fit their need for support) level. PMID- 26862037 TI - Angiotensin-converting enzyme 2 activator diminazene aceturate prevents lipopolysaccharide-induced inflammation by inhibiting MAPK and NF-kappaB pathways in human retinal pigment epithelium. AB - BACKGROUND: Retinal inflammation is a devastating pathological process in ocular diseases. Functional impairment of retinal pigment epithelium (RPE) is associated with inflammatory retinal diseases. Enhancing the protective axis namely ACE2/Ang (1-7)/Mas by activation of ACE2 presents anti-inflammatory properties. We investigated whether diminazene aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, prevented lipopolysaccharide (LPS)-induced inflammatory response by activating the protective axis and whether the effect was mediated by inhibiting the mitogen-activated protein kinase (MAPK) and the nuclear factor-kappaB (NF-kappaB) pathways. METHODS: Cell counting kit-8 (CCK-8) assay and real-time PCR were used to determine the optimum concentration and incubation time of DIZE. ARPE-19 cells and primary cultured human retinal pigment epithelia (hRPE) were incubated with or without 10 MUg/mL DIZE for 6 h before stimulated with 5 MUg/mL LPS for 24 h. The mRNA expression of inflammatory cytokines, AT1R, and AT2R was analyzed. The protein level of inflammatory cytokines, Ang II, and Ang-(1-7) was detected. Phosphorylation of p38 MAPK, extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphorylated transcription inhibition factor-kappaB-alpha (p-IkappaB-alpha) were measured. Inhibitors of MAPKs and NF-kappaB were added to verify the involvement of these pathways. A small interfering RNA (siRNA) targeted to ACE2 and a selective Ang-(1-7) antagonist A779 was used to confirm the role of ACE2 and the involvement of ACE2/Ang-(1-7)/Mas axis. RESULTS: DIZE remarkably increased the expression of ACE2 and inhibited the expression of IL-6, IL-8, and MCP-1 at both mRNA and protein levels in both RPE cell lines stimulated with LPS. Inhibitors of p38, ERK1/2, JNK, and NF-kappaB significantly decreased LPS-induced overproduction of IL-6, IL-8, and MCP-1. DIZE reduced the expression of Ang II and AT1R, whereas increased Ang-(1-7). Furthermore, DIZE downregulated the phosphorylation of p38MAPK, ERK1/2, JNK, and the activation of NF-kappaB upon stimulation with LPS. Downregulating ACE2 and pre-treatment with A779 abrogated the effects of DIZE on production of cytokines, the expression of Ang II, Ang-(1 7), AT1R, phosphorylation of MAPKs and activation of NF-kappaB. CONCLUSIONS: DIZE inhibits LPS-induced inflammatory response by activating ACE2/Ang-(1-7)/Mas axis in human RPE cells. The protective effect is mediated by inhibiting the p38MAPK, ERK1/2, JNK, and NF-kappaB pathways. PMID- 26862039 TI - Biofilm formation of Brazilian meticillin-resistant Staphylococcus aureus strains: prevalence of biofilm determinants and clonal profiles. AB - Biofilms plays an important role in medical-device-related infections. This study aimed to determine the factors that influence adherence and biofilm production, as well as the relationship between strong biofilm production and genetic determinants in clinical isolates of meticillin-resistant Staphylococcus aureus (MRSA). Fifteen strains carrying different chromosomal cassettes recovered from hospitalized patients were selected; five SCCmecII, five SCCmecIII and five SCCmecIV. The SCCmec type, agr group and the presence of the virulence genes (bbp, clfA, icaA, icaD, fnbB, bap, sasC and IS256) were assessed by PCR. PFGE and multilocus sequence typing (MLST) techniques were also performed. The initial adhesion and biofilm formation were examined by quantitative assays. The surface tension and hydrophobicity of the strains were measured by the contact angle technique to evaluate the association between these parameters and adhesion ability. SCCmecIII and IV strains were less hydrophilic, with a high value for the electron acceptor parameter and higher adhesion in comparison with SCCmecII strains. Only SCCmecIII strains could be characterized as strong biofilm producers. The PFGE showed five major pulsotypes (A-E); however, biofilm production was related to the dissemination of one specific PFGE clone (C) belonging to MLST ST239 (Brazilian epidemic clonal complex). The genes agrI, fnbB and IS256 in SCCmecIII strains were considered as genetic determinants associated with strong biofilm-formation by an ica-independent biofilm pathway. This study contributes to the understanding of biofilm production as an aggravating factor potentially involved in the persistence and severity of infections caused by multidrug-resistant MRSA belonging to this genotype. PMID- 26862041 TI - Fluid friction and wall viscosity of the 1D blood flow model. AB - We study the behavior of the pulse waves of water into a flexible tube for application to blood flow simulations. In pulse waves both fluid friction and wall viscosity are damping factors, and difficult to evaluate separately. In this paper, the coefficients of fluid friction and wall viscosity are estimated by fitting a nonlinear 1D flow model to experimental data. In the experimental setup, a distensible tube is connected to a piston pump at one end and closed at another end. The pressure and wall displacements are measured simultaneously. A good agreement between model predictions and experiments was achieved. For amplitude decrease, the effect of wall viscosity on the pulse wave has been shown as important as that of fluid viscosity. PMID- 26862040 TI - A rigid body model for the assessment of glenohumeral joint mechanics: Influence of osseous defects on range of motion and dislocation. AB - The purpose of this study was to employ subject-specific computer models to evaluate the interaction of glenohumeral range-of-motion and Hill-Sachs humeral head bone defect size on engagement and shoulder dislocation. We hypothesized that the rate of engagement would increase as defect size increased, and that greater shoulder ROM would engage smaller defects. Three dimensional computer models of 12 shoulders were created. For each shoulder, additional models were created with simulated Hill-Sachs defects of varying severities (XS=15%, S=22.5%, M=30%, L=37.5%, XL=45% and XXL=52.5% of the humeral head diameter, respectively). Rotational motion simulations without translation were conducted. The simulations ended if the defect engaged the anterior glenoid rim with resultant dislocation. The results showed that the rate of engagement was significantly different between defect sizes (0.00150). Serum vitamin D levels were classified as sufficient (>=30 ng/mL), insufficient (29-21 ng/mL), or deficient (<=20 ng/mL). RESULTS: A total of 105 patients met the inclusion criteria. Mild AD was diagnosed in 58 (55.2%) children, moderate in 24 (22.8%), and severe in 23 (21.9%). Vitamin D deficiency was observed in 45 individuals (42.9%). Of these, 24 (53.3%) had mild AD, 13 (28.9%) moderate, and 8 (17.7%) severe. Insufficient vitamin D levels were found in 45 (42.9%) individuals; 24 (53.3%) had mild AD, 9 (20.0%) moderate, and 12 (26.7%) severe. Of the 15 individuals (14.2%) with sufficient vitamin D levels, 10 (60.7%) had mild AD, 2 (13.3%) moderate, and 3 (20.0%) severe. The mean vitamin D level was 22.1 +/- 7.3 ng/mL in individuals with mild AD, 20.8 +/- 6.5 ng/mL in those with moderate AD, and 21.9 +/- 9.3 ng/mL in those with severe AD. Variables such as sex, age, skin phototype, season of the year, and bacterial infection were not significantly associated with vitamin D levels. CONCLUSION: Levels of 25-hydroxyvitamin D were deficient or insufficient in 85% of the children, but serum vitamin D concentrations were not significantly related to AD severity. PMID- 26862047 TI - Identification of Korean-specific SNP markers from whole-exome sequencing data. AB - Analysis of large numbers of single-nucleotide polymorphisms (SNPs) can increase individual discrimination power, and, particularly, it can supply important evidence for kinship or ethnic identification. We identified 300 Korean-specific SNPs from 306 Korean whole-exome sequencing (WES) data. Functionally significant SNPs (variants in splicing site, missense, nonsense, and exonic indels) were filtered out from the variant pool, and SNPs with minor allele frequencies (MAFs) of <0.3 in the 1000 Genomes (1000G) database but >0.3 in the Korean population were selected. Genotypes obtained from WES were confirmed by the Sanger sequencing method. The identified markers were evenly distributed throughout the autosomal chromosomes. All the SNPs were in the Hardy-Weinberg equilibrium with a mean MAF of 0.415 (0.161 in 1000G). The mean heterozygosities were 0.476 (observed) and 0.470 (experimental). The combined power of discrimination was very high. Korean MAFs in most SNPs were similar to those for the Chinese and Japanese populations, but were significantly higher than those for several other ethnic populations. These selected SNPs will be used to develop forensic markers and are expected to be widely used for additional individual identification, ethnic discrimination, and linkage analysis for kinship tests. PMID- 26862048 TI - Association between high-sensitivity C-reactive protein and hyperuricemia. AB - The aim of the study was to examine the cross-sectional association between high sensitivity C-reactive protein (hsCRP) and hyperuricemia (HU). The hsCRP was measured by latex turbidity method. Uric acid was detected on Beckman Coulter AU 5800. HU was defined as uric acid >=416 MUmol/L for the male population and >=360 MUmol/L for the female population. A multivariable logistic analysis model was applied to test the association after adjusting for a number of potential confounding factors. A total of 1935 subjects were included in this study. According to the multivariable regression model, the relative odds of the prevalence of HU were increased by 0.56 times in the third quintile (OR 1.56, 95 % CI 1.03-2.38, P = 0.04), 0.55 times in the fourth quintile (OR 1.55, 95 % CI 1.01-2.36, P = 0.04) and 0.96 times in the fifth quintile (OR 1.96, 95 % CI 1.29 2.98, P < 0.01) of hsCRP comparing with the lowest quintile, and P for trend was smaller than 0.01. In the male population, a positive association existed in the highest quintile of hsCRP (OR 1.66, 95 % CI 1.04-2.66, P = 0.04), and P for trend was 0.07. In the female population, the multivariable-adjusted ORs (95 % CI) of HU in the fourth and fifth quintile of hsCRP were 3.02 (95 % CI 1.09-8.35, P = 0.03) and 3.66 (95 % CI 1.36-9.89, P = 0.01), respectively, and P for trend was smaller than 0.01. The findings of this cross-sectional study suggest that the hsCRP level is positively associated with the prevalence of HU. Level of evidence Cross-sectional study, Level III. PMID- 26862049 TI - Smart coumarin-tagged imprinted polymers for the rapid detection of tamoxifen. AB - A signalling molecularly imprinted polymer was synthesised for easy detection of tamoxifen and its metabolites. 6-Vinylcoumarin-4-carboxylic acid (VCC) was synthesised from 4-bromophenol to give a fluorescent monomer, designed to switch off upon binding of tamoxifen. Clomiphene, a chlorinated analogue, was used as the template for the imprinting, and its ability to quench the coumarin fluorescence when used in a 1:1 ratio was demonstrated. Tamoxifen and 4 hydroxytamoxifen were also shown to quench coumarin fluorescence. Imprinted and non-imprinted polymers were synthesised using VCC, methacrylic acid as a backbone monomer and ethylene glycol dimethacrylate as cross-linker, and were ground and sieved to particle sizes ranging between 45 and 25 MUm. Rebinding experiments demonstrate that the imprinted polymer shows very strong affinity for both clomiphene and tamoxifen, while the non-imprinted polymer shows negligible rebinding. The fluorescence of the imprinted polymer is quenched by clomiphene, tamoxifen and 4-hydroxytamoxifen. The switch off in fluorescence of the imprinted polymer under these conditions could also be detected under a UV lamp with the naked eye, making this matrix suitable for applications when coupled with a sample preparation system. PMID- 26862051 TI - Breaking TADs: How Alterations of Chromatin Domains Result in Disease. AB - Spatial organization is an inherent property of the vertebrate genome to accommodate the roughly 2m of DNA in the nucleus of a cell. In this nonrandom organization, topologically associating domains (TADs) emerge as a fundamental structural unit that is thought to guide regulatory elements to their cognate promoters. In this review we summarize the most recent findings about TADs and the boundary regions separating them. We discuss how the disruption of these structures by genomic rearrangements can result in gene misexpression and disease. PMID- 26862050 TI - A novel strategy for the determination of polycyclic aromatic hydrocarbon monohydroxylated metabolites in urine using ultra-high-performance liquid chromatography with tandem mass spectrometry. AB - In this study, a novel analytical approach for the determination of 11 monohydroxylated polycyclic aromatic hydrocarbon metabolites (OH-PAHs) in urine was developed and validated. The rapid, simple and high-throughput sample preparation procedure based on ethyl acetate extraction and subsequent purification by dispersive solid-phase extraction (d-SPE) employing a Z-Sep sorbent is used for the first time. For the identification/quantification of target compounds, ultra-high-performance liquid chromatography (U-HPLC) interfaced with tandem mass spectrometry (MS/MS) was applied. The results of validation experiments performed on the Standard Reference Material (SRM) 3673 (organic contaminants in non-smokers' urine) were in accordance with the certified values. The method recoveries ranged from 77 to 114 % with the relative standard deviation lower than 20 % and the quantification limits in the range of 0.010-0.025 ng mL(-1) (except for benzo[a]pyren-3-ol with 0.9 ng mL(-1)). Within the pilot study, the new method was used for the analysis of OH-PAHs in 50 urine samples. The concentrations of SigmaOH-PAHs were in the range of 0.87-63 ng mL( 1) (1600-33,000 ng g(-1) creatinine), with naphthalen-2-ol (2-OH-NAP) and phenanthren-1-ol (1-OH-PHEN) being the most abundant exposure biomarkers detected in all samples. PMID- 26862052 TI - Longitudinal patterns of urine biomarkers in infants across gestational ages. AB - BACKGROUND: Urinary biomarkers may be indicators of acute kidney injury (AKI), although little is known of their developmental characteristics in healthy neonates across a full range of gestational age (GA). The purpose of this study was to examine patterns of urinary biomarkers across GA groups from birth to 3 months of age. METHODS: Fifty-two infants ranging from 24 to 41 weeks' GA had urine assayed from birth through 3 months of age for 7 biomarkers including albumin (ALB), beta-2-microglobulin (B2M), cystatin-C (CysC), epidermal growth factor (EGF), neutrophil-gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and uromodulin (UMOD). RESULTS: Of the seven urinary biomarkers, EGF and UMOD increased while others decreased with advancing GA. By 3 months of age, EGF and UMOD had increased in preterm infants to levels similar to those of term infants. UMOD/ml and EGF/ml appeared to be predominantly developmental biomarkers distinguishing estimated glomerular filtration rate (GFR) <30 ml/min/1.73 m(2) with receiver operator characteristic area under the curve (ROC-AUC) of 0.82; p = 0.002. When factored by urine creatinine CysC/cr + ALB/cr were the most significant functional markers with AUC = 0.79; p = 0.004; sensitivity 96 %; specificity 58 %. CONCLUSIONS: Among healthy neonates, urinary biomarkers vary with GA. These data support the use of urinary biomarkers in the assessment of normal kidney development in the absence of injury. PMID- 26862053 TI - The impact of estimated glomerular filtration rate equations on chronic kidney disease staging in pediatric renal or heart transplant recipients. AB - BACKGROUND: The aim of this study was to evaluate the performance of selected pediatric estimated glomerular filtration rate (eGFR) equations in relation to the clinical management of children after renal or heart transplantation or post chemotherapy treatment. METHODS: This study was a retrospective cross-sectional analysis of 61 children whose glomerular function (GFR) had been determined using a single-dose inulin clearance (iGFR) method. Eight equations for estimating the GFR were evaluated for bias, agreement, accuracy, and clinical stratification. RESULTS: The outcome of all eight eGFR equations differed from the value determined using the iGFR method, with the mean bias ranging from -3.4 to 20.7 ml/min/1.73 m(2) and 90 % accuracy ranging from 16 to 26 %. All eGFR equations overestimated renal function in patients with decreased kidney function as determined by the iGFR method and underestimated renal function in patients with normal kidney function. Consequently, based on the eGFR values, patients with low GFR values according to the iGFR method were staged in a less severe chronic kidney disease (CKD) category, and patients with normal GFR values according to the iGFR method were staged in a more severe CKD category. The percentage of correctly classified patients ranged from 32.6 to 41.6 %. CONCLUSIONS: In our cohort we found the CKiDIII equation to be the best alternative to calculating the GFR using the inulin clearance method, closely followed by the Hoste and the revised Grubb equations. The performances of all eight eGFR equations assessed were moderate at best and only slightly better than the easy-to-do bedside Schwartz equation. PMID- 26862054 TI - Netter: re-ranking gene network inference predictions using structural network properties. AB - BACKGROUND: Many algorithms have been developed to infer the topology of gene regulatory networks from gene expression data. These methods typically produce a ranking of links between genes with associated confidence scores, after which a certain threshold is chosen to produce the inferred topology. However, the structural properties of the predicted network do not resemble those typical for a gene regulatory network, as most algorithms only take into account connections found in the data and do not include known graph properties in their inference process. This lowers the prediction accuracy of these methods, limiting their usability in practice. RESULTS: We propose a post-processing algorithm which is applicable to any confidence ranking of regulatory interactions obtained from a network inference method which can use, inter alia, graphlets and several graph invariant properties to re-rank the links into a more accurate prediction. To demonstrate the potential of our approach, we re-rank predictions of six different state-of-the-art algorithms using three simple network properties as optimization criteria and show that Netter can improve the predictions made on both artificially generated data as well as the DREAM4 and DREAM5 benchmarks. Additionally, the DREAM5 E.coli. community prediction inferred from real expression data is further improved. Furthermore, Netter compares favorably to other post-processing algorithms and is not restricted to correlation-like predictions. Lastly, we demonstrate that the performance increase is robust for a wide range of parameter settings. Netter is available at http://bioinformatics.intec.ugent.be. CONCLUSIONS: Network inference from high throughput data is a long-standing challenge. In this work, we present Netter, which can further refine network predictions based on a set of user-defined graph properties. Netter is a flexible system which can be applied in unison with any method producing a ranking from omics data. It can be tailored to specific prior knowledge by expert users but can also be applied in general uses cases. Concluding, we believe that Netter is an interesting second step in the network inference process to further increase the quality of prediction. PMID- 26862055 TI - Behavioral Weight Loss Treatments for Individuals with Migraine and Obesity. AB - Migraine and obesity are each prevalent disorders involving significant personal and societal burden. Epidemiologic research demonstrates a link between migraine and obesity that is further substantiated by putative behavioral, psychosocial, and physiological mechanisms. As obesity is considered a modifiable risk factor for exacerbation of migraine, weight loss may be a particularly useful treatment option for people with comorbid migraine and obesity. Behavioral weight loss interventions complement existing behavioral treatments for migraine and offer patients evidence-based effective strategies for achieving weight loss that could help reduce frequency, severity, and impact of migraine attacks. PMID- 26862056 TI - A Japanese family with X-linked sideroblastic anemia affecting females and manifesting as macrocytic anemia. AB - X-linked sideroblastic anemia (XLSA) is a rare hereditary disorder that typically manifests in males as microcytic anemia. Here, we report a family with XLSA that affects females and manifests as macrocytic anemia. The proband was a Japanese woman harboring a heterozygous mutation c.679C>T in the ALAS2 gene. This mutation causes the amino acid substitution R227C, which disrupts the enzymatic activity of erythroid-specific delta-aminolevulinic acid synthase. The mutation was not detected in the ALAS2 complementary DNA from peripheral blood red blood cells of the proband, indicating that the cells were mostly derived from erythroblasts expressing wild-type ALAS2. The proband's mother, who had been diagnosed with myelodysplastic syndrome, also had XLSA with the same mutation. Clinicians should be aware that XLSA can occur not only in males but also in females, in whom it manifests as macrocytic anemia. PMID- 26862059 TI - CD10-positive myoepithelial cells are usually prominent around in situ lobular neoplasia of the breast and much less prominent or absent in DCIS. AB - AIMS: To study the relationship between the neoplastic cells of in situ lobular neoplasia (ILN) and ductal carcinoma in situ (DCIS) and the surrounding CD10 positive myoepithelial cells. MATERIALS AND METHODS: Twenty consecutive cases of ILN and 51 of DCIS were stained for CD10 using the immunoperoxidase technique. The presence of CD10-positive cells was assessed semiquantitatively on a scale of 0-3 where 0 indicates their absence and 3 indicates the presence of multiple layers, which can be focal. RESULTS: Ninety per cent of ILN cases scored 3, compared with none of DCIS (p=0.0001). There was a significant relationship between DCIS grade and CD10 score, with the mean scores being 1.43, 0.82 and 0.5 for low, intermediate and high grade, respectively. CD10-positive cells were always present around low-grade DCIS, but absent in 27% of high-grade cases. CD10 positive cells were more frequent in ER-positive than in ER-negative DCIS, and in HER2-negative than in HER2-positive cases, but the difference was not statistically significant. CONCLUSIONS: There is a distinct relationship between the type and grade of in situ neoplasia of the breast and the surrounding CD10 positive myoepithelial cells, suggesting the presence of a 'cross talk' between the two elements. PMID- 26862057 TI - Effects of salience-network-node neurofeedback training on affective biases in major depressive disorder. AB - Neural models of major depressive disorder (MDD) posit that over-response of components of the brain's salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, we tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham neurofeedback group, from pre- to post-training, participants in the real neurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. Our findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD. PMID- 26862061 TI - A comparison of the performance of seven key bibliographic databases in identifying all relevant systematic reviews of interventions for hypertension. AB - BACKGROUND: Bibliographic databases are the primary resource for identifying systematic reviews of health care interventions. Reliable retrieval of systematic reviews depends on the scope of indexing used by database providers. Therefore, searching one database may be insufficient, but it is unclear how many need to be searched. We sought to evaluate the performance of seven major bibliographic databases for the identification of systematic reviews for hypertension. METHODS: We searched seven databases (Cochrane library, Database of Abstracts of Reviews of Effects (DARE), Excerpta Medica Database (EMBASE), Epistemonikos, Medical Literature Analysis and Retrieval System Online (MEDLINE), PubMed Health and Turning Research Into Practice (TRIP)) from 2003 to 2015 for systematic reviews of any intervention for hypertension. Citations retrieved were screened for relevance, coded and checked for screening consistency using a fuzzy text matching query. The performance of each database was assessed by calculating its sensitivity, precision, the number of missed reviews and the number of unique records retrieved. RESULTS: Four hundred systematic reviews were identified for inclusion from 11,381 citations retrieved from seven databases. No single database identified all the retrieved systematic reviews for hypertension. EMBASE identified the most reviews (sensitivity 69 %) but also retrieved the most irrelevant citations with 7.2 % precision (Pr). The sensitivity of the Cochrane library was 60 %, DARE 57 %, MEDLINE 57 %, PubMed Health 53 %, Epistemonikos 49 % and TRIP 33 %. EMBASE contained the highest number of unique records (n = 43). The Cochrane library identified seven unique records and had the highest precision (Pr = 30 %), followed by Epistemonikos (n = 2, Pr = 19 %). No unique records were found in PubMed Health (Pr = 24 %) DARE (Pr = 21 %), TRIP (Pr = 10 %) or MEDLINE (Pr = 10 %). Searching EMBASE and the Cochrane library identified 88 % of all systematic reviews in the reference set, and searching the freely available databases (Cochrane, Epistemonikos, MEDLINE) identified 83 % of all the reviews. The databases were re-analysed after systematic reviews of non conventional interventions (e.g. yoga, acupuncture) were removed. Similarly, no database identified all the retrieved systematic reviews. EMBASE identified the most relevant systematic reviews (sensitivity 73 %) but also retrieved the most irrelevant citations with Pr = 5 %. The sensitivity of the Cochrane database was 62 %, followed by MEDLINE (60 %), DARE (55 %), PubMed Health (54 %), Epistemonikos (50 %) and TRIP (31 %). The precision of the Cochrane library was the highest (20 %), followed by PubMed Health (Pr = 16 %), DARE (Pr = 13 %), Epistemonikos (Pr = 12 %), MEDLINE (Pr = 6 %), TRIP (Pr = 6 %) and EMBASE (Pr = 5 %). EMBASE contained the most unique records (n = 34). The Cochrane library identified seven unique records. The other databases held no unique records. CONCLUSIONS: The coverage of bibliographic databases varies considerably due to differences in their scope and content. Researchers wishing to identify systematic reviews should not rely on one database but search multiple databases. PMID- 26862060 TI - Pseudomonas aeruginosa lectin LecB inhibits tissue repair processes by triggering beta-catenin degradation. AB - Pseudomonas aeruginosa is an opportunistic pathogen that induces severe lung infections such as ventilator-associated pneumonia and acute lung injury. Under these conditions, the bacterium diminishes epithelial integrity and inhibits tissue repair mechanisms, leading to persistent infections. Understanding the involved bacterial virulence factors and their mode of action is essential for the development of new therapeutic approaches. In our study we discovered a so far unknown effect of the P. aeruginosa lectin LecB on host cell physiology. LecB alone was sufficient to attenuate migration and proliferation of human lung epithelial cells and to induce transcriptional activity of NF-kappaB. These effects are characteristic of impaired tissue repair. Moreover, we found a strong degradation of beta-catenin, which was partially recovered by the proteasome inhibitor lactacystin. In addition, LecB induced loss of cell-cell contacts and reduced expression of the beta-catenin targets c-myc and cyclin D1. Blocking of LecB binding to host cell plasma membrane receptors by soluble l-fucose prevented these changes in host cell behavior and signaling, and thereby provides a powerful strategy to suppress LecB function. Our findings suggest that P. aeruginosa employs LecB as a virulence factor to induce beta-catenin degradation, which then represses processes that are directly linked to tissue recovery. PMID- 26862062 TI - Integrating candidate metabolites and biochemical factors to elucidate the action mechanism of Xue-sai-tong injection based on (1)H NMR metabolomics. AB - A strategy of integrating candidate metabolites with crucial biochemical factors was proposed in this study to discover relevant biological functions for interpreting the action mechanism of Traditional Chinese Medicines (TCM). This approach was applied to Xue-Sai-Tong injection (XST) to reveal the action mechanism based on the metabolic response in an ischemia/reperfusion (I/R) rat model by analyzing NMR profile. Partial least squares discriminate analysis (PLS DA) was used to compare metabolic profiles of serum samples and revealed nine metabolites altered by I/R injury could be restored to normal status (sham operated group) under the therapy of XST. The pathway enrichment analysis suggested the metabolic changes were mainly involved in pyruvate metabolism, glycolysis, and citrate cycle. The functional roles of the candidate metabolites were further identified by Pearson correlation analysis with the key biochemical factors in serum. The results indicated pyruvate, succinate, acetate and lysine showed significant associations with the oxidative stress factors. Elevated level of pyruvate was found as an essential metabolic response for the major effect of XST against I/R injury by enhancing glycolysis and overcoming the induced reactive oxygen species (ROS). This metabolomics approach provides a better understanding of the mechanisms of TCM and helps to develop a holistic view of TCM efficacy. PMID- 26862063 TI - Suboptimal Use of Oral Anticoagulants in Atrial Fibrillation: Has the Introduction of Direct Oral Anticoagulants Improved Prescribing Practices? AB - BACKGROUND AND OBJECTIVES: Atrial fibrillation (AF) and the associated risk of stroke are emerging epidemics throughout the world. Suboptimal use of oral anticoagulants for stroke prevention has been widely reported from observational studies. In recent years, direct oral anticoagulants (DOACs) have been introduced for thromboprophylaxis. We conducted a systematic literature review to evaluate current practices of anticoagulation in AF, pharmacologic features and adoption patterns of DOACs, their impacts on proportion of eligible patients with AF who receive oral anticoagulants, persisting challenges and future prospects for optimal anticoagulation. LITERATURE SOURCE AND SELECTION CRITERIA: In conducting this review, we considered the results of relevant prospective and retrospective observational studies from real-world practice settings. PubMed (MEDLINE), Scopus (RIS), Google Scholar, EMBASE and Web of Science were used to source relevant literature. There were no date limitations, while language was limited to English. Selection was limited to articles from peer reviewed journals and related to our topic. RESULTS: Most studies identified in this review indicated suboptimal use of anticoagulants is a persisting challenge despite the availability of DOACs. Underuse of oral anticoagulants is apparent particularly in patients with a high risk of stroke. DOAC adoption trends are quite variable, with slow integration into clinical practice reported in most countries; there has been limited impact to date on prescribing practice. CONCLUSION: Available data from clinical practice suggest that suboptimal oral anticoagulant use in patients with AF and poor compliance with guidelines still remain commonplace despite transition to a new era of anticoagulation featuring DOACs. PMID- 26862064 TI - Characterization of a new HLA-A allele, HLA-A*02:07:08, by cloning and sequencing. AB - In this report, we present a novel HLA-A*02:07 allele, HLA-A*02:07:08. HLA A*02:07:08 was identified in an individual of Han ethnicity in Hunan province, southern China. Following polymerase chain reaction-sequence-based typing (PCR SBT), this new allele was further confirmed by cloning and sequencing. HLA A*02:07:08 differs from HLA-A*02:07:01 by a single synonymous C to T substitution at nucleotide position 131 in exon 3. PMID- 26862066 TI - Fluoridated hydroxyapatite: Eu(3+) nanorods-loaded folate-conjugated D-alpha tocopheryl polyethylene glycol succinate (vitamin E TPGS) micelles for targeted imaging of cancer cells. AB - In this study, fluoridated hydroxyapatite: Eu(3+) nanorod-loaded folate conjugated TPGS micelles were prepared by thin-film hydration. The findings in this study demonstrate that micelles show improved dispersion, high stability, and excellent fluorescent property in aqueous solutions, suitable for targeted imaging of cancer cells with over-expressing folate receptors on their surface. The micelles designed in this study will be a promising tool for early detection of cancer. PMID- 26862068 TI - Transcutaneous CO2 monitoring: a new tool to identify spontaneous breathing trial failure during weaning from mechanical ventilation. A pilot cohort study. PMID- 26862069 TI - Septic shock due to Clostridium tertium in an immunocompetent patient following colitis without inflammatory bowel disease. PMID- 26862065 TI - beta-catenin-independent WNT signaling and Ki67 in contrast to the estrogen receptor status are prognostic and associated with poor prognosis in breast cancer liver metastases. AB - Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection and clinical relevance of biomarker analysis in metastatic tissue have barely been investigated. We previously demonstrated an impact of WNT signaling in breast cancer brain metastasis. This study aimed to investigate the value of established prognostic markers and WNT signaling components in liver metastases. Overall N = 34 breast cancer liver metastases (with matched primaries in 19/34 cases) were included in this retrospective study. Primaries and metastatic samples were analyzed for their expression of the estrogen (ER) and progesterone receptor, HER 2, Ki67, and various WNT signaling-components by immunohistochemistry. Furthermore, beta-catenin-dependent and -independent WNT scores were generated and analyzed for their prognostic value. Additionally, the influence of the alternative WNT receptor ROR on signaling and invasiveness was analyzed in vitro. ER positivity (HR 0.09, 95 % CI 0.01-0.56) and high Ki67 (HR 3.68, 95 % CI 1.12 12.06) in the primaries had prognostic impact. However, only Ki67 remained prognostic in the metastatic tissue (HR 2.46, 95 % CI 1.11-5.44). Additionally, the beta-catenin-independent WNT score correlated with reduced overall survival only in the metastasized situation (HR 2.19, 95 % CI 1.02-4.69, p = 0.0391). This is in line with the in vitro results of the alternative WNT receptors ROR1 and ROR2, which foster invasion. In breast cancer, the value of prognostic markers established in primary tumors cannot directly be translated to metastases. Our results revealed beta-catenin-independent WNT signaling to be associated with poor prognosis in patients with breast cancer liver metastasis. PMID- 26862070 TI - Thermal injury due to use of a forced air warming blanket during paediatric surgery. PMID- 26862071 TI - Commercial syringes of atropine: A cost-effective option in the operating room? PMID- 26862072 TI - Beware of using tranexamic acid in parturients with eclampsia. PMID- 26862073 TI - Improving the care of critically ill and postoperative patients with acute kidney injury. PMID- 26862074 TI - Unusual dialysis catheter position due to partial anomalous pulmonary venous return: Diagnosis and management. PMID- 26862075 TI - Diagnostic accuracy of the clinical feeding evaluation in detecting aspiration in children: a systematic review. AB - The aim of this systematic review is to determine the diagnostic accuracy of clinical feeding evaluation (CFE) compared to instrumental assessments in detecting oropharyngeal aspiration (OPA) in children. This is important to support clinical decision-making and to provide safe, cost-effective, higher quality care. All published and unpublished studies in all languages assessing the diagnostic accuracy of CFE compared to videofluoroscopic swallowing study (VFSS) and/or fibre-optic endoscopic examination of swallowing (FEES) in detecting OPA in paediatric populations were sought. Databases were searched from inception to April 2015. Grey literature, citations, and references were also searched. Two independent reviewers extracted and analysed data. Accuracy estimates were calculated. Research reports were translated into English as required. Six studies examining the diagnostic accuracy of CFE using VFSS and/or FEES were eligible for inclusion. Sample sizes, populations studied, and CFE characteristics varied widely. The overall methodological quality of the studies, assessed with QUADAS-2, was considered 'low'. Results suggested that CFEs trialling liquid consistencies might provide better accuracy estimates than CFEs trialling solids exclusively. This systematic review highlights the critical lack of evidence on the accuracy of CFE in detecting OPA in children. Larger well designed primary diagnostic test accuracy studies in this area are needed to inform dysphagia assessment in paediatrics. PMID- 26862076 TI - Effects of co-occurring Wolbachia and Spiroplasma endosymbionts on the Drosophila immune response against insect pathogenic and non-pathogenic bacteria. AB - BACKGROUND: Symbiotic interactions between microbes and animals are common in nature. Symbiotic organisms are particularly common in insects and, in some cases, they may protect their hosts from pathogenic infections. Wolbachia and Spiroplasma endosymbionts naturally inhabit various insects including Drosophila melanogaster fruit flies. Therefore, this symbiotic association is considered an excellent model to investigate whether endosymbiotic bacteria participate in host immune processes against certain pathogens. Here we have investigated whether the presence of Wolbachia alone or together with Spiroplasma endosymbionts in D. melanogaster adult flies affects the immune response against the virulent insect pathogen Photorhabdus luminescens and against non-pathogenic Escherichia coli bacteria. RESULTS: We found that D. melanogaster flies carrying no endosymbionts, those carrying both Wolbachia and Spiroplasma, and those containing Wolbachia only had similar survival rates after infection with P. luminescens or Escherichia coli bacteria. However, flies carrying both endosymbionts or Wolbachia only contained higher numbers of E. coli cells at early time-points post infection than flies without endosymbiotic bacteria. Interestingly, flies containing Wolbachia only had lower titers of this endosymbiont upon infection with the pathogen P. luminescens than uninfected flies of the same strain. We further found that the presence of Wolbachia and Spiroplasma in D. melanogaster up-regulated certain immune-related genes upon infection with P. luminescens or E. coli bacteria, but it failed to alter the phagocytic ability of the flies toward E. coli inactive bioparticles. CONCLUSION: Our results suggest that the presence of Wolbachia and Spiroplasma in D. melanogaster can modulate immune signaling against infection by certain insect pathogenic and non-pathogenic bacteria. Results from such studies are important for understanding the molecular basis of the interactions between endosymbiotic bacteria of insects and exogenous microbes. PMID- 26862077 TI - Cytokine-release kinetics of platelet-rich plasma according to various activation protocols. AB - OBJECTIVES: This study was conducted to evaluate the cytokine-release kinetics of platelet-rich plasma (PRP) according to different activation protocols. METHODS: Two manual preparation procedures (single-spin (SS) at 900 g for five minutes; double-spin (DS) at 900 g for five minutes and then 1500 g for 15 minutes) were performed for each of 14 healthy subjects. Both preparations were tested for platelet activation by one of three activation protocols: no activation, activation with calcium (Ca) only, or calcium with a low dose (50 IU per 1 ml PRP) of thrombin. Each preparation was divided into four aliquots and incubated for one hour, 24 hours, 72 hours, and seven days. The cytokine-release kinetics were evaluated by assessing PDGF, TGF, VEGF, FGF, IL-1, and MMP-9 concentrations with bead-based sandwich immunoassay. RESULTS: The concentration of cytokine released from PRP varied over time and was influenced by various activation protocols. Ca-only activation had a significant effect on the DS PRPs (where the VEGF, FGF, and IL-1 concentrations were sustained) while Ca/thrombin activation had effects on both SS and DS PRPs (where the PDGF and VEGF concentrations were sustained and the TGF and FGF concentrations were short). The IL-1 content showed a significant increase with Ca-only or Ca/thrombin activation while these activations did not increase the MMP-9 concentration. CONCLUSION: The SS and DS methods differed in their effect on cytokine release, and this effect varied among the cytokines analysed. In addition, low dose of thrombin/calcium activation increased the overall cytokine release of the PRP preparations over seven days, relative to that with a calcium-only supplement or non activation.Cite this article: Professor J. H. Oh. Cytokine-release kinetics of platelet-rich plasma according to various activation protocols. Bone Joint Res 2016;5:37-45. doi: 10.1302/2046-3758.52.2000540. PMID- 26862079 TI - Alcohol Screening and Intervention Among United States Adults who Attend Ambulatory Healthcare. AB - BACKGROUND: There is limited data on the extent to which indicated alcohol interventions are delivered in U.S. ambulatory care settings. OBJECTIVE: To assess the receipt of alcohol-related services, including assessment of use, advice to reduce drinking, and information about alcohol treatment, during ambulatory care visits. DESIGN: Secondary data analysis of the 2013 National Survey on Drug Use and Health, a cross-sectional, nationally representative survey of civilians in the non-institutionalized U.S. general population (response rate 71.7 %). PARTICIPANTS: Adult ambulatory care users in the public use data file who did not obtain emergency or inpatient services (n = 17,266). MAIN MEASURES: Measurements included respondents' alcohol consumption, heavy episodic drinking, alcohol use disorder, healthcare use, and receipt of alcohol related interventions. KEY RESULTS: Approximately 71.1 % of ambulatory care users received an alcohol assessment. Among past-month heavy episodic drinkers without an alcohol use disorder who reported receiving an alcohol assessment, 4.4 % were advised to cut back. Among individuals with alcohol abuse and alcohol dependence who reported receiving an alcohol assessment, 2.9 % and 7.0 %, respectively, were offered information about treatment. CONCLUSIONS: Rates of alcohol screening and assessment were relatively high among adults who attended healthcare visits, but rates of intervention were low, even when individuals were assessed for use. Efforts are needed to expand delivery of interventions when patients are identified as positive for risky drinking, hazardous alcohol use, and alcohol use disorders during ambulatory care visits. PMID- 26862080 TI - Co-expression of chaperones from P. furiosus enhanced the soluble expression of the recombinant hyperthermophilic alpha-amylase in E. coli. AB - The extracellular alpha-amylase from the hyperthermophilic archaeum Pyrococcus furiosus (PFA) is extremely thermostable and of an industrial importance and interest. PFA aggregates and accumulates as insoluble inclusion bodies when expressed as a heterologous protein at a high level in Escherichia coli. In the present study, we investigated the roles of chaperones from P. furiosus in the soluble expression of recombinant PFA in E. coli. The results indicate that co expression of PFA with the molecular chaperone prefoldin alone significantly increased the soluble expression of PFA. Although, co-expression of other main chaperone components from P. furiosus, such as the small heat shock protein (sHSP) or chaperonin (HSP60), was also able to improve the soluble expression of PFA to a certain extent. Co-expression of chaperonin or sHSP in addition to prefoldin did not further increase the soluble expression of PFA. This finding emphasizes the biotechnological potentials of the molecular chaperone prefoldin from P. furiosus, which may facilitate the production of recombinant PFA. PMID- 26862081 TI - Enhanced resistance to Sclerotinia sclerotiorum in Brassica napus by co expression of defensin and chimeric chitinase genes. AB - Sclerotinia stem rot caused by Sclerotinia sclerotiorum is one of the major fungal diseases of Brassica napus L. To develop resistance against this fungal disease, the defensin gene from Raphanus sativus and chimeric chit42 from Trichoderma atroviride with a C-terminal fused chitin-binding domain from Serratia marcescens were co-expressed in canola via Agrobacterium-mediated transformation. Twenty transformants were confirmed to carry the two transgenes as detected by polymerase chain reaction (PCR), with 4.8 % transformation efficiency. The chitinase activity of PCR-positive transgenic plants were measured in the presence of colloidal chitin, and five transgenic lines showing the highest chitinase activity were selected for checking the copy number of the transgenes through Southern blot hybridisation. Two plants carried a single copy of the transgenes, while the remainder carried either two or three copies of the transgenes. The antifungal activity of two transgenic lines that carried a single copy of the transgenes (T4 and T10) was studied by a radial diffusion assay. It was observed that the constitutive expression of these transgenes in the T4 and T10 transgenic lines suppressed the growth of S. sclerotiorum by 49 % and 47 %, respectively. The two transgenic lines were then let to self-pollinate to produce the T2 generation. Greenhouse bioassays were performed on the transgenic T2 young leaves by challenging with S. sclerotiorum and the results revealed that the expression of defensin and chimeric chitinase from a heterologous source in canola demonstrated enhanced resistance against sclerotinia stem rot disease. PMID- 26862082 TI - Diabetology and oncology meet in a network model: union is strength. AB - Diabetes and cancer are increasingly common conditions, and the management of cancer patients with diabetes is often challenging. Diabetes in cancer patients poses several complex clinical issues, including which treatment is suitable to control hyperglycemia, how to better counteract glucocorticoid-induced hyperglycemia, and how to manage nutritional problems of cachectic patients and glucose variability linked to artificial nutrition. A key aspect to consider is the patients' position on the trajectory of the oncologic disease, both to establish which level of glycemic control should be pursued and to decide the most suitable antidiabetic treatment to recommend. Endocrinologists are rarely involved in the management of patients with advanced cancer. Furthermore, lack of guidelines results in a "trial-and-error" approach, often with suboptimal disease management. Lastly, cancer survivors represent a frequently underestimated category of patients at higher cardiometabolic risk. A practical solution for these challenges lies in the implementation of care networks based on a close partnership and ongoing communication between oncologists, endocrinologists, and nutritionists, placing the patient at the center of the care process. At the same time, universities and scientific societies should play a key role in promoting research into areas of intersection of oncology and endocrinology, in raising awareness of common possibilities of primary and secondary prevention of metabolic and oncologic diseases, as well as specific challenges of managing diabetes and cancer, and proper training of health workers, while also supporting the shared implementation of effective management strategies. PMID- 26862083 TI - Mating system and pollen dispersal in Eugenia dysenterica (Myrtaceae) germplasm collection: tools for conservation and domestication. AB - Eugenia dysenterica DC. (Myrtaceae) is a perennial tree producing edible fruits and ornamental flowers of potential value widely distributed in Brazilian "Cerrados" (savannas), but available genetic resources and potential for future breeding programs must be evaluated. Here we evaluated the reproductive system and pollen-mediated gene flow in one generation of Eugenia dysenterica germplasm collection of Agronomy School, Federal University of Goias (in Goiania city, Central Brazil). We collected leaves from all adults from the germplasm collection (682 plants) and seeds (542) from 23 mother-trees. Genotypes were obtained for seven microsatellite loci. Genetic diversity was high and did not significantly differ between adults (H e = 0.777) and progeny arrays (H e = 0.617). Our results showed that E. dysenterica has an allogamous mating system in the germplasm collection (t m = 0.957), but with high and significant biparental inbreeding (t m - t s = 0.109). Because sibs are very close to each other, mating between closely related individuals is likely. Paternity correlation was also relatively high, indicating a 11.9 % probability that a randomly chosen pair of outcrossed progeny from the same array are full sibs. The maximum pollen dispersal distance (224 m), estimated using assignment test, corresponded to the boundaries of the orchard. We were able to assign the paternity to only 64 % of the 349 seeds analyzed, indicating potential pollen immigration to the germplasm collection. The variance effective population size estimated for one maternal family in the germplasm collection (N ev = 3.42) is very close to the theoretical maximum value for half-sibs (Nev = 4.0). Because E. dysenterica has a long life cycle and generation time, the maintenance of an effective population size of at least 100 in the germplasm collection is suggested, which can be achieved by maintaining a seed-trees number around 30 individuals. PMID- 26862084 TI - A mixed-method evaluation of the feasibility and acceptability of a telehealth based parent-mediated intervention for children with autism spectrum disorder. AB - Research within the autism spectrum disorder field has called for the use of service delivery models that are able to more efficiently disseminate evidence based practices into community settings. This study employed telehealth methods in order to deliver an Internet-based, parent training intervention for autism spectrum disorder, ImPACT Online. This study used mixed-methods analysis to create a more thorough understanding of parent experiences likely to influence the adoption and implementation of the program in community settings. Specific research questions included (1) What are parents' perceptions of the online program? (2) How does ImPACT Online compare to other services that parents are accessing for their children? And (3) Do parents' experience in, and perceptions of, the program differ based on whether they received a therapist-assisted version of the program? Results from 28 parents of a child with autism spectrum disorder indicate that parents saw improvements in their child's social communication skills and their own competence during the course of the program, regardless of whether they received therapist assistance. However, qualitative interviews indicate that parents who received therapist assistance were more likely endorse the acceptability and observability of the program. These findings support the potential for Internet-based service delivery to more efficiently disseminate evidence-based parent training interventions for autism spectrum disorder. PMID- 26862085 TI - First evidence of the feasibility of gaze-contingent attention training for school children with autism. AB - A number of authors have suggested that attention control may be a suitable target for cognitive training in children with autism spectrum disorder. This study provided the first evidence of the feasibility of such training using a battery of tasks intended to target visual attentional control in children with autism spectrum disorder within school-based settings. Twenty-seven children were recruited and randomly assigned to either training or an active control group. Of these, 19 completed the initial assessment, and 17 (9 trained and 8 control) completed all subsequent training sessions. Training of 120 min was administered per participant, spread over six sessions (on average). Compliance with the training tasks was generally high, and evidence of within-task training improvements was found. A number of untrained tasks to assess transfer of training effects were administered pre- and post-training. Changes in the trained group were assessed relative to an active control group. Following training, significant and selective changes in visual sustained attention were observed. Trend training effects were also noted on disengaging visual attention, but no convincing evidence of transfer was found to non-trained assessments of saccadic reaction time and anticipatory looking. Directions for future development and refinement of these new training techniques are discussed. PMID- 26862086 TI - Mammary Adipose Tissue-Derived Lysophospholipids Promote Estrogen Receptor Negative Mammary Epithelial Cell Proliferation. AB - Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein-coupled receptors, has been implicated in many physiologic and pathologic processes, including cancer. LPA is converted from lysophosphatidylcholine (LPC) by the secreted phospholipase autotaxin (ATX). Although various cell types can produce ATX, adipocyte-derived ATX is believed to be the major source of circulating ATX and also to be the major regulator of plasma LPA levels. In addition to ATX, adipocytes secrete numerous other factors (adipokines); although several adipokines have been implicated in breast cancer biology, the contribution of mammary adipose tissue-derived LPC/ATX/LPA (LPA axis) signaling to breast cancer is poorly understood. Using murine mammary fat conditioned medium, we investigated the contribution of LPA signaling to mammary epithelial cancer cell biology and identified LPA signaling as a significant contributor to the oncogenic effects of the mammary adipose tissue secretome. To interrogate the role of mammary fat in the LPA axis during breast cancer progression, we exposed mammary adipose tissue to secreted factors from estrogen receptor-negative mammary epithelial cell lines and monitored changes in the mammary fat pad LPA axis. Our data indicate that bidirectional interactions between mammary cancer cells and mammary adipocytes alter the local LPA axis and increase ATX expression in the mammary fat pad during breast cancer progression. Thus, the LPC/ATX/LPA axis may be a useful target for prevention in patients at risk of ER-negative breast cancer. Cancer Prev Res; 9(5); 367-78. (c)2016 AACR. PMID- 26862088 TI - Photopreventive Effect and Mechanism of AZD4547 and Curcumin C3 Complex on UVB Induced Epidermal Hyperplasia. AB - Aggressive cutaneous squamous cell carcinoma (cSCC) of the skin is the second most common type of skin cancer in the United States due to high exposure to ultraviolet B (UVB) radiation. In our previous studies, Curcumin C3 complex (C3), a standardized preparation of three curcumonoids, delayed UVB-induced tumor incidence and inhibited multiplicity. Exposure to UVB activates mTOR and FGFR signaling that play a key role in skin tumorigenesis. The purpose of this study was to investigate the efficacy of C3 complex to afford protection against acute UVB-induced hyperproliferation by targeting the mTOR and FGFR signaling pathways. Pretreatment with C3 complex significantly inhibited UVB-induced FGF-2 induction, FGF-2-induced cell proliferation, progression and colony formation, mTORC1 and mTORC2 activation, and FGFR2 phosphorylation in the promotion-sensitive JB6 cells epithelial cells. Further, FGFR was critical for UVB-induced mTOR activation, suggesting an important role of FGFR2 in UVB-induced mTOR signaling. SKH-1 mice pretreated with C3 (15 mg/kg/b.w.) for 2 weeks followed by a single exposure to UVB (180 mj/cm(2)) significantly attenuated UVB-induced mTORC1, mTORC2, and FGFR2 activation. To further assess the role of FGFR in UVB-induced hyperproliferation, SKH-1 mice were pretreated with AZD4547 (5 mg/kg/b.w.); a selective pan-FGFR kinase inhibitor followed by single exposure to UVB (180 mj/cm(2)). AZD4547 significantly inhibited UVB-induced mTORC1 and mTORC2 activation, epidermal hyperplasia and hyperproliferation. Our studies underscore the importance of FGFR signaling in UVB-induced acute skin changes and the role of FGFR/mTOR signaling in mediating the effects of C3 complex in the pathogenesis of skin cancer. PMID- 26862089 TI - A glimpse into this issue. PMID- 26862091 TI - Effect of lanosterol on human cataract nucleus. AB - AIM: To study the effect of lanosterol on age-related cataractous human lens nuclei. MATERIALS AND METHODS: Forty age-related cataractous nuclei removed during manual small incision cataract surgery were obtained and randomly immersed in 25 mM lanosterol solution or in control solution and stored at room temperature for 6 days. Pre- and post-immersion photographs were graded by two masked observers and collated for the regression or progression of lens opacity. RESULTS: Both lanosterol and control groups showed progression or no change in the lens opacity at the end of 6 days. CONCLUSION: Lanosterol 25 mM solution did not reverse opacification of human age-related cataractous nuclei. PMID- 26862090 TI - Characterization of the parasite-induced lesions in the posterior segment of the eye. AB - Ocular lesions are frequently associated with different parasitic infections. The classes of infection include protozoa, nematodes, cestodes, and ectoparasites. Ocular parasitic infections can manifest in any part of the eye; the disease manifestations are frequently characterized as either posterior or anterior eye disease. Parasite-induced lesions may be due to damage directly caused by the parasite, indirect pathology caused by toxic products or the immune response initiated by infectious parasitism. This review characterized the parasite induced lesions in the posterior segment of the eye. Prompt diagnosis and early treatment of these lesions can reduce ocular morbidity. The method of the literature search was conducted on PubMed, Elsevier Scopus database, and Google Scholar with no limitation on the year of publication databases. It was limited to English articles published for ocular lesions in clinical studies and was focused on parasitic infections of the eye. PMID- 26862087 TI - Whole-Genome Sequencing of Salivary Gland Adenoid Cystic Carcinoma. AB - Adenoid cystic carcinomas (ACC) of the salivary glands are challenging to understand, treat, and cure. To better understand the genetic alterations underlying the pathogenesis of these tumors, we performed comprehensive genome analyses of 25 fresh-frozen tumors, including whole-genome sequencing and expression and pathway analyses. In addition to the well-described MYB-NFIB fusion that was found in 11 tumors (44%), we observed five different rearrangements involving the NFIB transcription factor gene in seven tumors (28%). Taken together, NFIB translocations occurred in 15 of 25 samples (60%, 95% CI, 41%-77%). In addition, mRNA expression analysis of 17 tumors revealed overexpression of NFIB in ACC tumors compared with normal tissues (P = 0.002). There was no difference in NFIB mRNA expression in tumors with NFIB fusions compared with those without. We also report somatic mutations of genes involved in the axonal guidance and Rho family signaling pathways. Finally, we confirm previously described alterations in genes related to chromatin regulation and Notch signaling. Our findings suggest a separate role for NFIB in ACC oncogenesis and highlight important signaling pathways for future functional characterization and potential therapeutic targeting. PMID- 26862093 TI - Comparison of incidence of ptosis after combined phacotrabeculectomy with mitomycin C and phacoemulsification. AB - OBJECTIVE: To compare the incidence of upper eyelid blepharoptosis after combined phacotrabeculectomy with mitomycin C and phacoemulsification surgeries and the relationship of bleb morphology to the incidence of ptosis. DESIGN: Retrospective observation study. PARTICIPANTS: We included 46 patients after combined phacotrabeculectomy and 44 patients with phacoemulsification in the former group, and all eyes underwent a standardized two-site surgery with intra-operative mitomycin C. MATERIALS AND METHODS: Postoperative ptosis was defined as a reduction of upper marginal reflex distance 2 mm in the operated eye compared to the fellow eye. Trabeculectomy bleb measurements were carried out using anterior segment optical coherence tomography (VisanteTM, Carl Zeiss Meditec, Dublin, CA, USA) which included bleb height and total area of the bleb. RESULTS: There were 8 eyes (17.4%) and 5 eyes (11.4%) with postoperative ptosis in the phacotrabeculectomy and phacoemulsification groups, respectively (P = 0.342). In multivariate regression analysis, reduced total bleb area was significantly associated with upper eyelid ptosis after adjusting for age, gender, and type of anesthesia. The trend seemed to show that increased bleb height was also associated with ptosis, but this did not reach statistical significance. CONCLUSIONS: Incidence of persistent ptosis after phacoemulsification combined with trabeculectomy and mitomycin C is similar compared to stand alone phacoemulsification surgery in a multiethnic Asian population. Bleb morphology may play an important role in postoperative ptosis development and should be considered in the evaluation of upper eyelid blepharoptosis. PMID- 26862092 TI - Effect of alpha-2-agonist premedication on intraocular pressure after selective laser trabeculoplasty. AB - AIM: To determine the effect of alpha-2-agonist (AA) premedication (PM) on intraocular pressure (IOP) following selective laser trabeculoplasty (SLT). METHODS: Retrospective cohort study of all patients undergoing 360 degrees SLT at an institution with two prevalent practice patterns consisting of SLT performed with PM and without premedication (NPM) with AA. The association between pre- and post-operative IOP was evaluated using a linear regression model in 49 (59%) PM and 34 (41%) NPM eyes. RESULTS: The prevalence of IOP elevations up to 5 mmHg 1 h postoperatively was similar in both groups, occurring in 18% of PM and in 15% of NPM. Elevations above 5 mmHg were seen in 4% of PM and 8% of NPM (P = 0.732). After correcting for age, gender, diagnosis, number of medications, and preoperative IOP, the presence or absence of AA PM had no significant association with any postoperative IOP (P > 0.5). CONCLUSION: The practice of using AAs before SLT and measuring IOP at 1 h has not been validated yet adds to expenses and workflow burden. Our retrospective study showed no significant correlation between PM and postoperative or longer-term IOP. IOP at 1 h should be measured in patients who cannot tolerate transient pressure elevations. Further studies are needed to elucidate this relationship. PMID- 26862094 TI - Retrospective hospital-based analysis of age-related macular degeneration patterns in India: 5-year follow-up. AB - PURPOSE: To provide a detailed analysis of age-related macular degeneration (AMD) with a 5-year follow-up at a Tertiary Eye Care Center in India. METHODS: In this retrospective institutional study, 408 eyes of 204 subjects (100 males) with a diagnosis of AMD with minimum 5-year follow-up were included. Data collected included demographics, details of the ocular exam, special investigations performed, treatment offered, complications, and systemic diseases, if any. RESULTS: The median age was 74.24 +/- 8.23 years. Median follow-up was 5.77 years. The visual acuity (VA) at baseline and last visit was 0.74 +/- 0.12 (Snellen's equivalent 20/100) and 0.54 +/- 0.12 logarithm of the minimum angle of resolution (Snellen's equivalent 20/50; P = 0.032) in patients with choroidal neovascular membrane (CNVM). The most common complaint was decreased vision (94.5%). AMD (any stage) was found to be bilateral in 93% of patients at baseline and 197 patients (96.56%) at 5 years. Seventeen eyes had active CNVM (12 of these were occult) at presentation. At baseline, 43 eyes had a disciform scar. Three hundred twenty-one eyes had dry AMD at baseline (geographic atrophy - 12 [3.7%] eyes). Five-year conversion rate into wet AMD and geographic atrophy was 2.87% and 3.12%. Median number of anti-vascular endothelial growth factor injections administered per patient was 2.8 +/- 1.2. CNVM bilaterality was low (7.5%). CONCLUSION: Patients with AMD in India presented later in the course of the disease. Bilateral advanced AMD and geographic atrophy were uncommon. Five-year conversion rate into wet AMD and geographic atrophy was 2.87% and 3.12%. PMID- 26862095 TI - Intraocular cytokines in retinal vein occlusion and its relation to the efficiency of anti-vascular endothelial growth factor therapy. AB - PURPOSE: To analyze the change in the concentration of intraocular cytokines (ICs) in patients with retinal vein occlusion (RVO) before and after intravitreal ranibizumab therapy (IVR), and to find the correlations of IC with clinical activity of RVO and efficiency of treatment. MATERIALS AND METHODS: Forty-four patients aged 46-79 years old (mean age: 60.7 +/- 7.5 years old) with RVO and macular edema (18 patients - with central RVO, 26 - with branch RVO) treated with IVR were included into the study. The concentrations of 27 cytokines were simultaneously measured in aqueous humor by flow fluorometry using Bio-Plex Pro Human Cytokine Panel, 27-Plex (Bio-Rad Laboratories, USA) at baseline and after the first IVR. Control group consisted of 20 age-matched patients. RESULTS: The levels of 11 cytokines (vascular endothelial growth factor [VEGF], receptor antagonist interleukin-1, interleukin-6 [IL-6], IL-8, IL-9, IL-10, IL-12r70, IL 13, IL-15, monocyte chemotactic protein-1 [MCP-1], regulated on activation, normal T expressed and secreted) were significantly (P < 0.05) different compared to control and significantly (P < 0.05) changed after IVR both in central and branch RVO. The patients were divided into two groups: the first -"effective" and the second - "partially effective" therapy. The second group characterized by the higher concentrations of VEGF, IL-8, IL-10, IL-17, and MCP-1 at baseline compared to the first group. CONCLUSION: The patients with RVO were characterized by the increased levels of VEGF and other pro- and anti-inflammatory cytokines and chemokines. Aqueous concentration of cytokines were different in patients with central and branch RVO and significantly changed after IVR. Insufficient response to IVR was associated with activation of immune-inflammatory processes. PMID- 26862096 TI - Choroidal thickness in diabetic patients of Indian ethnicity. AB - PURPOSE: To evaluate choroidal thickness (CT) change in various grades of diabetic retinopathy (DR) in comparison to age-matched healthy subjects. METHODS: This prospective observational study included 227 eyes of 125 subjects with diabetes (study group: 58 females) and 197 eyes of 110 age-matched healthy subjects (control group: 66 females). Collected data included age, gender, duration of diabetes, glycemic control, comprehensive ocular examination, fundus photography, and CT measurement on spectral domain ocular coherence tomography using enhanced depth imaging. RESULTS: Mean age in the study group was 57.0 +/- 9.37 years (43-73 years). The mean age was 41.48 +/- 5.43 years in the control group. Subjects with diabetes with (252.8 +/- 55.6 microns) and without (261.71 +/- 51.8 microns) retinopathy had significantly thinner choroids when compared to the control group (281.7 +/- 47.7 microns; P = 0.032). Seventy-four of 227 eyes did not have any evidence of DR, 89 eyes had features of nonproliferative diabetic retinopathy (NPDR), and 33 eyes had treatment naive proliferative diabetic retinopathy (PDR). Thirty-one PDR eyes had received previous laser photocoagulation. Subjects with diabetes without retinopathy had a greater subfoveal choroidal thickness (SFCT) than subjects with diabetes with retinopathy (P < 0.001). Eyes with PDR (243.9 +/- 56.2 microns) had thinner SFCT than those with NPDR (238.98 +/- 111.23 microns). There was no difference in the SFCT between treated (laser photocoagulation done; 251.784 +/- 103.72 microns) and treatment naive PDR (258.405 +/- 89.47 microns, P = 0.23). CONCLUSIONS: Control eyes had greater SFCT compared to subjects with diabetes, with and without retinopathy. The thinning progressed with increasing severity of DR. Choroidal thinning may contribute to DR pathogenesis. PMID- 26862097 TI - Combined occlusion of branch retinal artery and vein secondary to prepapillary arterial loops. AB - A middle-aged diabetic and hypertensive man presented with diminished vision in the left eye. Fundus examination revealed prepapillary arterial loops, but with features of venous rather than arterial occlusion. Fluorescein angiography and optical coherence tomography confirmed the presence of a branch retinal vein occlusion along with two branch retinal artery occlusions. The resultant macular edema responded well to intravitreal triamcinolone and laser photocoagulation though the visual improvement was moderate. PMID- 26862098 TI - A case of giant nodular posterior scleritis mimicking choroidal malignancy. AB - To report a case of giant nodular posterior scleritis mimicking a choroidal tumor. A 42-year-old lady with systemic hypertension presented with a 1-week history of unilateral visual loss, pain and redness in her left eye. Examination showed sectoral anterior episcleritis in her left eye as well as a dome-shaped choroidal mass at the inferior-temporal periphery, associated with retinal hemorrhages and subretinal fluid. Systemic evaluation and imaging of the choroidal mass were performed and could not rule out amelanotic choroidal melanoma. At the same time, she was prescribed a 2-week course of oral nonsteroidal anti-inflammatory drug (NSAID) for her sectoral anterior episcleritis. The choroidal mass was found to have resolved completely right before her scheduled fine needle biopsy. Diagnosis of nodular posterior scleritis and a trial of oral NSAID can be considered in patients presenting with a choroidal mass before any invasive procedure. PMID- 26862099 TI - Unilateral sequential papillophlebitis and central retinal artery occlusion in a young healthy patient. AB - A 23-year-old girl presented to the clinic with metamorphopsia and photopsia in her left eye. After detailed ophthalmic examination, central retinal vein occlusion with optic disc edema was detected in that eye. Three days after diagnosis, the patient returned to our clinic with visual acuity decrease. Central retinal artery occlusion sparing cilioretinal artery was detected. All the laboratory tests were normal except for heterozygous methylenetetrahydrofolate reductase mutation (A1298C genotypes) and an indefinite Lyme disease seropositivity. Symptoms and visual disturbance recovered without any further treatment other than acetylsalicylic acid for prophylaxis. PMID- 26862100 TI - Minimal gauge vitrectomy for optic disc pit maculopathy: Our results. AB - The purpose of the study was to describe the surgical technique and clinical outcomes of pars plana vitrectomy without laser or gas tamponade in cases with optic disc pit maculopathy at our centre. Six eyes of six consecutive patients presenting with unilateral optic disc pit maculopathy were enrolled. Preoperative optical coherence tomography (OCT) was performed to determine the presence and extent of schisis and macular detachment. All eyes underwent 23-gauge pars plana vitrectomy with induction of posterior vitreous detachment (PVD) and internal limiting membrane (ILM) peeling and eyes were closed under fluid. Patients were followed up for at least 12 months post-surgery. Median age of patients was 22.5 years. Five of six eyes had neurosensory detachment (NSD) at the presentation; whereas, inner layer schisis was present in all patients. None of the patients had any evidence of vitreomacular or vitreopapillary adhesion or PVD either clinically or on OCT. Inner and outer retinal schisis resolved in all eyes after follow-up of at least 6 months. Resolution of subretinal fluid in eyes with NSD was seen in 4 of 5 eyes. There was a significant visual acuity improvement from mean preoperative visual acuity of 0.79 logarithm of the minimum angle of resolution (logMAR) units to 0.36 logMAR units at 12 months (P = 0.001). Thus, vitrectomy with ILM peeling and PVD induction alone could achieve good functional outcomes in cases with optic disc pit maculopathy. PMID- 26862101 TI - Neoadjuvant chemotherapy for invasive squamous cell carcinoma of the conjunctiva: A case report. AB - A 40-year-old male presented with an orbital extension of conjunctival squamous cell carcinoma (SCC). The orbital mass was seen protruding outward from the left palpebral fissure overhanging the lower eyelid, completely obscuring the globe and lower lid. The patient gave a history of excision biopsy, which was histopathologically diagnosed as ocular surface squamous neoplasia. He also gave a history of tumor recurrence, which gradually progressed to assume the form of the presently visible orbital mass. Computed tomography of the orbits showed the mass extending into the left orbit causing superior displacement of the globe. After a negative locoregional and systemic metastatic screening, neoadjuvant intravenous systemic chemotherapy with cisplatin and 5-fluorouracil were initiated in an attempt to reduce the size of the tumor. Three cycles of tri weekly chemotherapy resulted in a significant reduction of the orbital tumor size with the globe and the lower lid being visible, thus making a lid-sparing orbital exenteration possible. The patient subsequently underwent an orbital exenteration and at 6-month follow-up, the patient was free from local and regional disease. To our knowledge, this is the first reported case where systemic neoadjuvant chemotherapy has been used to reduce the size of invasive SCC with orbital extension, thereby permitting a lid-sparing orbital exenteration. PMID- 26862102 TI - Temperature control role of the choroid may affect choroidal thickness after dynamic exercise. PMID- 26862103 TI - Authors' response. PMID- 26862104 TI - Comment on: Acute visual loss with ophthalmoplegia after spinal surgery--Acid Base imbalance induced glaucoma in pediatric patients. PMID- 26862105 TI - Comment on: Donate eyes, not patients! PMID- 26862106 TI - Authors' response. PMID- 26862107 TI - Comment on: Alternate description of waveform: Pulsus bisferiens. PMID- 26862108 TI - Reproducibility of hormone-driven regional grey matter volume changes in women using SPM8 and SPM12. AB - Aim of this work was to evaluate the reproducibility of hormone driven regional grey matter volume differences in women, and their correlations with premenstrual symptoms, as determined by voxel-based morphometry (VBM). After data quality control, a total of 138 T1-weighted MR images were included in this longitudinal study, and were analyzed as three different subgroups. Women with a natural menstrual cycle were scanned at three time-points: follicular, ovulatory and luteal phase. Two groups of women, using androgenic and anti-androgenic hormonal contraceptives, respectively, were scanned twice: during the pill-free week and during pill intake. Additionally, subjects were asked to complete a "daily rating of severity of problems" questionnaire, to quantify premenstrual symptoms. All data were analyzed using SPM8 and SPM12 with identical parameter settings. In the natural menstrual cycle group, the regional grey matter volume of the insula is larger at ovulation, as compared to the luteal phase. Premenstrual symptoms correlate differently with regional grey matter volumes between women with a natural cycle and hormonal contraceptive users. Changes in hormonal environment can to various extents affect VBM findings in women. We suggest that researchers take these confounding factors into account while applying this technique, to avoid heterogeneity in data acquisition and to safeguard the sensitivity of findings. Additionally, we suggest validating the consistency of results using more than one software package. PMID- 26862109 TI - Accumulation of Ag and Cu in Amanita strobiliformis and characterization of its Cu and Ag uptake transporter genes AsCTR2 and AsCTR3. AB - Macrofungi can accumulate in their sporocarps remarkably high concentrations of Cu and Ag. We have previously demonstrated that the non-essential Ag is in the ectomycorrhizal, Ag-hyperaccumulating Amanita strobiliformis sequestered by 3.4 kDa metallothioneins (MTs) produced as AsMT1a, 1b and 1c isoforms. Here, we describe two populations of wild-grown A. strobiliformis sporocarps, which showed certain correlation between the concentrations of accumulated Ag (284 +/- 64 and 67 +/- 15 mg kg(-1)) and Cu (76 +/- 13 and 30 +/- 12 mg kg(-1)), suggesting that an overlap may exist in the cell biology of Ag and Cu in this species. Metal speciation analysis revealed that the intracellular Cu in the sporocarps of both populations was, like Ag, associated with the 3.4-kDa MTs. A search of A. strobiliformis transcriptome for sequences encoding proteins of the Cu transporter (CTR) family identified four AsCTR cDNAs, which were, like AsMT1s, confirmed in both populations. The predicted AsCTR proteins showed homology to vacuolar (AsCTR1 and AsCTR4) and plasma membrane (AsCTR2 and AsCTR3) CTRs. Heterologous expression of AsCTR2, AsCTR3 and their translational fusions with green fluorescent protein (GFP) in Cu uptake-deficient S. cerevisiae indicated that both AsCTRs are functional Cu and Ag uptake transporters: recombinant genes complemented growth defects and increased Cu and Ag uptake rates in yeasts and the GFP-tagged protein localized to the cell periphery. Site directed mutagenesis revealed the importance of the conserved-among-CTRs M-X3-M motif for the AsCTR2- and AsCTR3-mediated transport of both Cu and Ag. These results provide the first evidence that fungal CTRs can recognize Ag for transport. PMID- 26862111 TI - Caesarean delivery is associated with higher risk of depressive symptoms, pain and sexual dysfunction. PMID- 26862112 TI - Continuity of midwifery care models improve outcomes for young women and babies. PMID- 26862113 TI - Blood gene expression studies in migraine: Potential and caveats. AB - BACKGROUND: Global gene expression analysis may be used to obtain insights into the functional processes underlying migraine. However, there is a shortage of high-quality post-mortem brain tissue samples for genetic analysis. One approach is to use a more accessible tissue as a surrogate, such as peripheral blood. PURPOSE: Discuss the benefits and caveats of blood genomic profiling in migraine and its potential application in the development of biomarkers of migraine susceptibility and outcome. Demonstrate the utility of blood-based expression profiles in migraine by analysing pilot Illumina HT-12 expression data from 76 (38 case, 38 control) whole-blood samples. CONCLUSION: Current evidence suggests peripheral blood is a biologically valid substrate for genetic studies of migraine, and may be used to identify biomarkers and therapeutic pathways. Pilot blood gene expression data confirm that expression profiles significantly differ between migraine case and non-migraine control individuals. PMID- 26862110 TI - Clinical and laboratory variability in a cohort of patients diagnosed with type 1 VWD in the United States. AB - von Willebrand disease (VWD) is the most common inherited bleeding disorder, and type 1 VWD is the most common VWD variant. Despite its frequency, diagnosis of type 1 VWD remains the subject of debate. In order to study the spectrum of type 1 VWD in the United States, the Zimmerman Program enrolled 482 subjects with a previous diagnosis of type 1 VWD without stringent laboratory diagnostic criteria. von Willebrand factor (VWF) laboratory testing and full-length VWF gene sequencing was performed for all index cases and healthy control subjects in a central laboratory. Bleeding phenotype was characterized using the International Society on Thrombosis and Haemostasis bleeding assessment tool. At study entry, 64% of subjects had VWF antigen (VWF:Ag) or VWF ristocetin cofactor activity below the lower limit of normal, whereas 36% had normal VWF levels. VWF sequence variations were most frequent in subjects with VWF:Ag <30 IU/dL (82%), whereas subjects with type 1 VWD and VWF:Ag >=30 IU/dL had an intermediate frequency of variants (44%). Subjects whose VWF testing was normal at study entry had a similar rate of sequence variations as the healthy controls (14%). All subjects with severe type 1 VWD and VWF:Ag <=5 IU/dL had an abnormal bleeding score (BS), but otherwise BS did not correlate with VWF:Ag. Subjects with a historical diagnosis of type 1 VWD had similar rates of abnormal BS compared with subjects with low VWF levels at study entry. Type 1 VWD in the United States is highly variable, and bleeding symptoms are frequent in this population. PMID- 26862114 TI - Hypoxic Signaling and the Cellular Redox Tumor Environment Determine Sensitivity to MTH1 Inhibition. AB - Cancer cells are commonly in a state of redox imbalance that drives their growth and survival. To compensate for oxidative stress induced by the tumor redox environment, cancer cells upregulate specific nononcogenic addiction enzymes, such as MTH1 (NUDT1), which detoxifies oxidized nucleotides. Here, we show that increasing oxidative stress in nonmalignant cells induced their sensitization to the effects of MTH1 inhibition, whereas decreasing oxidative pressure in cancer cells protected against inhibition. Furthermore, we purified zebrafish MTH1 and solved the crystal structure of MTH1 bound to its inhibitor, highlighting the zebrafish as a relevant tool to study MTH1 biology. Delivery of 8-oxo-dGTP and 2 OH-dATP to zebrafish embryos was highly toxic in the absence of MTH1 activity. Moreover, chemically or genetically mimicking activated hypoxia signaling in zebrafish revealed that pathologic upregulation of the HIF1alpha response, often observed in cancer and linked to poor prognosis, sensitized embryos to MTH1 inhibition. Using a transgenic zebrafish line, in which the cellular redox status can be monitored in vivo, we detected an increase in oxidative pressure upon activation of hypoxic signaling. Pretreatment with the antioxidant N-acetyl-L cysteine protected embryos with activated hypoxia signaling against MTH1 inhibition, suggesting that the aberrant redox environment likely causes sensitization. In summary, MTH1 inhibition may offer a general approach to treat cancers characterized by deregulated hypoxia signaling or redox imbalance. Cancer Res; 76(8); 2366-75. (c)2016 AACR. PMID- 26862116 TI - Our better angels and black boxes. PMID- 26862115 TI - Detection of an Immunogenic HERV-E Envelope with Selective Expression in Clear Cell Kidney Cancer. AB - VHL-deficient clear cell renal cell carcinomas (ccRCC), the most common form of kidney cancer, express transcripts derived from the novel human endogenous retrovirus HERV-E (named CT-RCC HERV-E). In this study, we define a transcript encoding the entire envelope gene of HERV-E as expressed selectively in ccRCC tumors, as distinct from normal kidney tissues or other tumor types. Sequence analysis of this envelope transcript revealed long open reading frames encoding putative surface and transmembrane envelope proteins. Retroviral envelopes are known to be capable of eliciting immunity in humans. Accordingly, we found that HLA-A*0201-restricted peptides predicted to be products of the CT-RCC HERV-E envelope transcript-stimulated CD8(+) T cells, which could recognize HLA-A*0201 positive HERV-E-expressing kidney tumor cells. Overall, our results offer evidence of unique HERV-E envelope peptides presented on the surface of ccRCC cells, offering potentially useful tumor-restricted targets for T-cell-based immunotherapy of kidney cancer. Cancer Res; 76(8); 2177-85. (c)2016 AACR. PMID- 26862117 TI - Radiofrequency energy in the arthroscopic treatment of knee chondral lesions: a systematic review. AB - INTRODUCTION: Cartilage debridement is one of the recommended procedures for the management of chondral defects. Radiofrequency probes allow to debride the cartilage, but may induce subchondral bone necrosis. SOURCES OF DATA: Medline, Cochrane and Google Scholar were searched to identify studies on arthroscopic debridement of the articular cartilage of the knee using radiofrequency chondroplasty. The methodological quality of the studies was assessed using the Coleman methodology score (CMS). AREAS OF AGREEMENT: Monopolar and bipolar radiofrequency devices provide significantly better clinical outcomes, especially for patients with high-grade chondral lesions, compared with mechanical shaver only. Despite the original concerns regarding subchondral bone necrosis, low complication rates are reported. AREAS OF CONTROVERSY: Heterogeneity in terms of type of device does not allow sound comparison of the published results. There is lack of evidence on the long-term effects of radiofrequency chondroplasty. GROWING POINTS: Study methodology should be improved: the average Coleman methodology score was 56.2 out of 100. RESEARCH: More comparative, well-designed and larger cohort trials are needed to ascertain whether radiofrequency chondroplasty offers long-term benefits over other simpler and more economical alternatives. PMID- 26862118 TI - Experiences of Patients With Rheumatoid Arthritis: A Qualitative Study. AB - Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that greatly impacts one's physical and psychosocial well-being. The purpose of this study was to explore the experiences and support needs of adult patients living with RA. A descriptive qualitative study was conducted, and 16 adults with RA were interviewed from October 2013 to January 2014. The transcribed data were analyzed using thematic analysis. Five themes were identified: altered physical capacity and well-being, psychological and emotional challenges, changes in social life, coping strategies, and support received and further support needs. This study provided insights into the experiences and support needs of patients with RA in Singapore. Physical and psychosocial challenges experienced by patients affected their daily and social activities. Patients' needs for variety of support should be addressed. PMID- 26862120 TI - Sun exposure guidance should be tailored to individuals, says NICE. PMID- 26862122 TI - The use of HeartQoL in patients with coronary heart disease: Association with risk factors and European reference values. The EUROASPIRE IV study of the European Society of Cardiology. AB - BACKGROUND: HeartQoL is a recently developed core health-related quality of life instrument for patients with coronary heart disease. The current study aims to investigate its association with patients' coronary risk profile and to provide reference values for patients with coronary heart disease across Europe. DESIGN: Analyses are based on the EUROASPIRE IV (EUROpean Action on Secondary and Primary prevention through Intervention to Reduce Events) cross-sectional survey. METHODS: Patients with a diagnosis of coronary heart disease were examined and interviewed six months to three years after their coronary event. The HeartQoL questionnaire was completed by 7261 coronary heart disease patients. Reference values were calculated and the association with the coronary risk profile was assessed. RESULTS: Significantly worse outcomes were observed in higher-risk patient groups. Both metabolic and behavioural risk factors were associated with worse HeartQoL outcomes. Further, the HeartQoL scores decreased as the number of risk factors increased. The mean global reference values in males were 2.27 +/- 0.65 (<60 years), 2.30 +/- 0.61 (between 60 and 69 years) and 2.19 +/- 0.64 (>=70 years). Likewise, in females, the respective global HeartQoL reference values were 2.02 +/- 0.67, 2.01 +/- 0.66 and 1.83 +/- 0.70. The ceiling effect in males was 11.4%, 10.4% and 7.4% for the three age classes respectively, whereas in females the ceiling effect was 5.2%, 3.5% and 1.9%, respectively. CONCLUSION: HeartQoL scores were associated with patients' coronary risk profile. The reference values may help other researchers to interpret HeartQoL scores. Further research should focus on the minimal important difference needed to evaluate the effect of therapies and lifestyle changes. PMID- 26862123 TI - Perinatal air pollution exposure and development of asthma from birth to age 10 years. AB - Within-city variation in air pollution has been associated with childhood asthma development, but findings have been inconsistent. We examined whether perinatal air pollution exposure affected asthma onset during "pre-school and "school age" periods in a population-based birth cohort.65,254 children born between 1999 and 2002 in the greater Vancouver metropolitan region were followed until age 10 years using linked administrative health databases. Asthma cases were sex- and age-matched to five randomly chosen controls. Associations between exposure to air pollutants estimated with different methods (interpolation (inverse-distance weighted (IDW)), land use regression, proximity) and incident asthma during the pre-school (0-5 years) and school age (6-10 years) periods were estimated with conditional logistic regression.6948 and 1711 cases were identified during the pre-school and school age periods, respectively. Following adjustment for birthweight, gestational period, household income, parity, breastfeeding at discharge, maternal age and education, asthma risk during the pre-school years was increased by traffic pollution (adjusted odds ratio using IDW method per interquartile increase (95% CI): nitric oxide 1.06 (1.01-1.11), nitrogen dioxide 1.09 (1.04-1.13) and carbon monoxide 1.05 (1.01-1.1)). Enhanced impacts were observed amongst low-term-birthweight cases. Associations were independent of surrounding residential greenness.Within-city air pollution variation was associated with new asthma onset during the pre-school years. PMID- 26862121 TI - Ataxia telangiectasia mutated in cardiac fibroblasts regulates doxorubicin induced cardiotoxicity. AB - AIMS: Doxorubicin (Dox) is a potent anticancer agent that is widely used in the treatment of a variety of cancers, but its usage is limited by cumulative dose dependent cardiotoxicity mainly due to oxidative damage. Ataxia telangiectasia mutated (ATM) kinase is thought to play a role in mediating the actions of oxidative stress. Here, we show that ATM in cardiac fibroblasts is essential for Dox-induced cardiotoxicity. METHODS AND RESULTS: ATM knockout mice showed attenuated Dox-induced cardiotoxic effects (e.g. cardiac dysfunction, apoptosis, and mortality). As ATM was expressed and activated predominantly in cardiac fibroblasts, fibroblast-specific Atm-deleted mice (Atm(fl/fl);Postn-Cre) were generated to address cell type-specific effects, which showed that the fibroblast is the key lineage mediating Dox-induced cardiotoxicity through ATM. Mechanistically, ATM activated the Fas ligand, which subsequently regulated apoptosis in cardiomyocytes at later stages. Therapeutically, a potent and selective inhibitor of ATM, KU55933, when administered systemically was able to prevent Dox-induced cardiotoxicity. CONCLUSION: ATM-regulated effects within cardiac fibroblasts are pivotal in Dox-induced cardiotoxicity, and antagonism of ATM and its functions may have potential therapeutic implications. PMID- 26862124 TI - Obstructive lung function in idiopathic pulmonary fibrosis. PMID- 26862125 TI - Linking data on work, health and lifestyle to explain socio-occupational inequality in Danish register-based incidence of diabetes. AB - AIMS: This study aimed to combine three consecutive cohorts representative of the general working population to estimate the lifestyle, work and health of the entire Danish working population and to explore the influence of these factors on socio-occupational inequality in relation to incident diabetes over ten years. METHODS: This study linked the National Danish Diabetes Register with (a) three questionnaire rounds (1995, 2000, 2005) on work, health and lifestyle from the Danish Work Environment Cohort Study (DWECS) among 6823 representative Danish workers aged 30-59 years and (b) the different socio-occupational groups of the entire Danish population aged 30-59 years (n=1,833,756). The relative risk (RR) was calculated using a Poisson regression. RESULTS: In DWECS, none of the investigated job factors was associated with incident diabetes. Lifestyle factors in terms of smoking (RR = 1.35; 95% confidence interval (CI) 1.07-1.70), high body mass index (overweight RR = 2.81; 95% CI 2.11-3.74 and obesity RR = 7.49; 95% CI 5.46-10.28) were risk factors for incident diabetes. When adjusted for health and lifestyle, there was no difference in diabetes risk among socio occupational groups in DWECS. In the entire working population, there was a negative socio-occupational gradient for the risk of diabetes. Compared with professionals, workers in elementary occupations had the highest ten-year risk (RR = 2.06; 95% CI 2.01-2.12). CONCLUSIONS WE FOUND A SIGNIFICANT NEGATIVE SOCIO OCCUPATIONAL GRADIENT IN THE RISK OF INCIDENT DIABETES HOWEVER, LIFESTYLE RATHER THAN WORK ENVIRONMENT APPEARS TO BE THE MOST IMPORTANT FACTOR AND ADJUSTING FOR THIS ALMOST ELIMINATED THE SOCIO-OCCUPATIONAL INEQUALITY FOR THE DEVELOPMENT OF DIABETES. PMID- 26862126 TI - Sharp decrease in observed cerebrovascular mortality may be due to certification and coding. AB - AIMS AND METHODS: Being easily available and having good coverage and comparability, official mortality statistics are used very widely. This in turn is because the definitions of mortality and methods of pertinent data collection are coordinated worldwide by the World Health Organization. In Estonia, registered cerebrovascular mortality has dropped 50% since 2000. A less dramatic decrease has been observed in nearly all EU Member States. To find out if this development can be explained by changing certification and coding practices, we counted all mentions of cerebrovascular diseases in the Estonian Causes of Death Registry database between 2004 and 2013 and analyzed the selection of the underlying cause of death. RESULTS: We found that the sharp decrease in registered cerebrovascular mortality was by a half due to an increased selection of hypertension as the underlying cause of death. In cases where a cerebrovascular disease was mentioned and selected the underlying cause of death, the mean number of diagnoses per record was 2.45, in cases where a cerebrovascular disease was mentioned, but hypertension selected the underlying cause of death, the mean number of diagnoses was 3.15. CONCLUSIONS THE CHOICE OF THE UNDERLYING CAUSE OF DEATH REGISTERED IN OFFICIAL STATISTICS DEPENDS ON THE LEVEL OF DETAILS PROVIDED IN A DEATH CERTIFICATE, AS WELL AS UPDATES TO CODING RULES AND USE OF MODERN QUALITY ASSURANCE INSTRUMENTS IN DATA PRODUCTION. PMID- 26862127 TI - Prevalence of Helicobacter pylori infection among preschool children in Latvia: no significant decrease in prevalence during a ten year period. AB - AIMS: Published data show a trend of decreasing prevalence of Helicobacter pylori in Eastern European countries due to socioeconomic changes. The aim of this study was to determine the prevalence of H. pylori infection among children in Latvia and to compare these results with previous studies in the same population. The risk factors associated with infection were also analysed. METHODS: Preschool children in kindergartens and primary health care centres were investigated using a stool antigen test. Their parents were asked to fill out a questionnaire about possible risk factors. Statistical analysis included Pearson's chi(2) test and linear regression analysis. RESULTS: The prevalence of H. pylori infection determined by the monoclonal stool antigen test in children aged 1-6 years (median 5 years) was 15.5% (15/101) (95% confidence interval 8.67-23.48%). In the regression analysis, H. pylori positivity was significantly negatively associated with the consumption of imported fruit at least once per week (p=0.02). CONCLUSIONS THE PREVALENCE OF H PYLORI IN THE STUDIED POPULATION HAS NOT DECREASED SIGNIFICANTLY DURING THE LAST DECADE AND IS STILL ASSOCIATED WITH SOCIOECONOMIC FACTORS THE ROLE OF SOME DIETARY FACTORS EG THE CONSUMPTION OF FRUIT IN THE SPREAD OF INFECTION SHOULD BE STUDIED FURTHER. PMID- 26862128 TI - A useful irrigated tip to cannulate distal coronary sinus. PMID- 26862129 TI - The role of Dementia Champion in dementia care: Its aspirations, development and training needs (innovative practice). AB - BACKGROUND: The conceptualisation and development of the role of Dementia Champions in clinical practice is ongoing, and dementia specific training has a significant impact on the scope of the role. AIM: This survey aimed to elicit Dementia Champions' views on their role and associated training needs. METHODS: Data were collected via an online survey. FINDINGS: Of 188, 34 Dementia Champions (response rate 18%) participated. Most perceived dementia awareness training as useful, but limited. Areas suggested for further development were context specific skills training, education programmes that were formally recognised, and clarification around the expectations of the role. CONCLUSION: Expectations of 'champion roles' in dementia need to be re-visited, specifically in relation to the remit of the role and the level of education, preparation and support required for Dementia Champions to become change agents in dementia care. PMID- 26862130 TI - Associations between social network characteristics, cognitive function, and quality of life among residents in a dementia special care unit: A pilot study. AB - Social integration has a significant influence on physical and mental health. Older adults experience an increased risk of social isolation as their social networks contract. The purpose of this study is to examine associations between dementia special care unit residents' overall well-being and cognition with structural aspects of their coresident relationships. Design and Methods Measures of social network structure were calculated from self-reported social contact data within three cohorts of residents in one dementia special care unit. Pearson correlations were used to describe associations between overall quality of life and cognition, with network characteristics indicative of social integration. Results Approximately half the ties sent or received were reciprocated and positive associations were found between social integration and quality of life. However, inconsistent associations were found between social integration and cognitive function. Friendship ties were more frequent between people of adjacent cognitive status categories. In addition, comparing across personal networks, residents tended to be tied to residents of higher quality of life status (43.3%, n = 13 personal networks) as opposed to lower (30%, n = 9 networks) or same (26.7%, n = 8 networks). There is a strong positive correlation between quality of life and respondent's betweenness centrality, suggesting that individuals with high quality of life tend to be important intermediaries between others in the community. Implications Among the "oldest old," quality of life and cognitive function are unevenly distributed, yet these health indicators tend to cluster in social networks. This reinforces that while quality of life may be highly individual, it is in part linked to relationships with others. PMID- 26862132 TI - Endocervical and vaginal tuberculosis: series of three cases. PMID- 26862131 TI - Bacteriological quality of the wastewater used for irrigation at the vegetable farms in Korle-bu Teaching Hospital, Accra Metropolis, Ghana. AB - Many developing countries, including Ghana, are water stressed. As such, farmers, particularly those in urban areas, have adopted the use of wastewater for irrigation. This study evaluated the bacteriological water quality of the wastewater used for irrigation in the vegetable farms at Korle-Bu Teaching Hospital (KBTH), Accra Metropolis, Ghana. In all, 40 wastewater samples were collected and analysed bacteriologically using the total aerobic plate count method. The isolated bacteria were identified biochemically using Bergey's manual for determinative bacteriology. Mean total bacterial colony count values in the range of 2.75-4.44 * 105 CFU/100 mL were isolated which far exceeds values of 1 * 103/100 mL recommended by the World Health Organization (WHO) for unrestricted irrigation of crops likely to be eaten raw. Enterobacter cloacae (51.4%), Klebsiella sp. (24.1%), Pseudomonas aeruginosa (11.3%), Salmonella typhi (10.6%), Escherichia coli (2.2%) and Proteus sp. (0.4%) were the predominant bacteria isolated. Growers should use treated wastewater for farming while processors and consumers should minimize contamination risks of produce from the vegetable farms/garden to the plate. PMID- 26862133 TI - What Are Youth Asking About Drugs? A Report of NIDA Drug Facts Chat Day. AB - The current study analyzes a sample of questions about drugs asked online by youth who participated in the National Institute on Drug Abuse's (NIDA) "Drug Facts Chat Day." The types of drugs youth asked about were coded into 17 substance categories, and the topics they raised were coded into seven thematic categories. The top five queried drugs were marijuana (16.4%), alcohol (8.5%), tobacco (6%), cocaine (5.7), and pharmaceutical drugs (4.5%). The effects of drug use, experience of being high, the addictiveness of drugs, pharmacology, and drug sales were among the more common types of questions to emerge but varied depending on the substance. These findings show the types of information young people are seeking about drugs and have clear implications to inform youth drug education programs. PMID- 26862134 TI - Combined analysis of job and task benzene air exposures among workers at four US refinery operations. AB - Workplace air samples analyzed for benzene at four US refineries from 1976 to 2007 were pooled into a single dataset to characterize similarities and differences between job titles, tasks and refineries, and to provide a robust dataset for exposure reconstruction. Approximately 12,000 non-task (>180 min) personal samples associated with 50 job titles and 4000 task (<180 min) samples characterizing 24 tasks were evaluated. Personal air sample data from four individual refineries were pooled based on a number of factors including (1) the consistent sampling approach used by refinery industrial hygienists over time, (2) the use of similar exposure controls, (3) the comparability of benzene content of process streams and end products, (4) the ability to assign uniform job titles and task codes across all four refineries, and (5) our analysis of variance (ANOVA) of the distribution of benzene air concentrations for select jobs/tasks across all four refineries. The jobs and tasks most frequently sampled included those with highest potential contact with refinery product streams containing benzene, which reflected the targeted sampling approach utilized by the facility industrial hygienists. Task and non-task data were analyzed to identify and account for significant differences within job-area, task-job, and task-area categories. This analysis demonstrated that in general, areas with benzene containing process streams were associated with greater benzene air concentrations compared to areas with process streams containing little to no benzene. For several job titles and tasks analyzed, there was a statistically significant decrease in benzene air concentration after 1990. This study provides a job and task-focused analysis of occupational exposure to benzene during refinery operations, and it should be useful for reconstructing refinery workers' exposures to benzene over the past 30 years. PMID- 26862135 TI - RNA-induced silencing attenuates G protein-mediated calcium signals. AB - Phospholipase Cbeta (PLCbeta) is activated by G protein subunits in response to environmental stimuli to increase intracellular calcium. In cells, a significant portion of PLCbeta is cytosolic, where it binds a protein complex required for efficient RNA-induced silencing called C3PO (component 3 promoter of RISC). Binding between C3PO and PLCbeta raises the possibility that RNA silencing activity can affect the ability of PLCbeta to mediate calcium signals. By use of human and rat neuronal cell lines (SK-N-SH and PC12), we show that overexpression of one of the main components of C3PO diminishes Ca(2+) release in response to Galphaq/PLCbeta stimulation by 30 to 40%. In untransfected SK-N-SH or PC12 cells, the introduction of siRNA(GAPDH) [small interfering RNA(glyceraldehyde 3 phosphate dehydrogenase)] reduces PLCbeta-mediated calcium signals by ~30%, but addition of siRNA(Hsp90) (heat shock protein 90) had little effect. Fluorescence imaging studies suggest an increase in PLCbeta-C3PO association in cells treated with siRNA(GAPDH) but not siRNA(Hsp90). Taken together, our studies raise the possibility that Ca(2+) responses to extracellular stimuli can be modulated by components of the RNA silencing machinery.-Philip, F., Sahu, S., Golebiewska, U., Scarlata, S. RNA-induced silencing attenuates G protein-mediated calcium signals. PMID- 26862136 TI - Case-Based Reasoning for Insulin Bolus Advice. AB - BACKGROUND: Insulin bolus calculators assist people with Type 1 diabetes (T1D) to calculate the amount of insulin required for meals to achieve optimal glucose levels but lack adaptability and personalization. We have proposed enhancing bolus calculators by the means of case-based reasoning (CBR), an established problem-solving methodology, by individualizing and optimizing insulin therapy for various meal situations. CBR learns from experiences of past similar meals, which are described in cases through a set of parameters (eg, time of meal, alcohol, exercise). This work discusses the selection, representation and effect of case parameters used for a CBR-based Advanced Bolus Calculator for Diabetes (ABC4D). METHODS: We analyzed the usage and effect of selected parameters during a pilot study (n = 10), where participants used ABC4D for 6 weeks. Retrospectively, we evaluated the effect of glucose rate of change before the meal on the glycemic excursion. Feedback from study participants about the choice of parameters was obtained through a nonvalidated questionnaire. RESULTS: Exercise and alcohol were the most frequently used parameters, which was congruent with the feedback from study participants, who found these parameters most useful. Furthermore, cases including either exercise or alcohol as parameter showed a trend in reduction of insulin at the end of the study. A significant difference ( P < .01) was found in glycemic outcomes for meals where glucose rate of change was rising compared to stable rate of change. CONCLUSIONS: Results from the 6-week study indicate the potential benefit of including parameters exercise, alcohol and glucose-rate of change for insulin dosing decision support. PMID- 26862139 TI - The role of nitrogen and phosphorus in regulating Phormidium sp. (cyanobacteria) growth and anatoxin production. AB - Benthic proliferations of the cyanobacteria Phormidium can cover many kilometres of riverbed. Phormidium can produce neurotoxic anatoxins and ingestion of benthic mats has resulted in numerous animal poisonings in the last decade. Despite this, there is a poor understanding of the environmental factors regulating growth and anatoxin production. In this study, the effects of nitrogen and phosphorus on the growth of two Phormidium strains (anatoxin-producing and non-anatoxin-producing) were examined in batch monocultures. Cell concentrations were significantly reduced under reduced nitrogen (ca. <0.100 mM) and phosphorus conditions (ca. <0.003 mM). Cell concentrations and maximum growth rates were higher for the non anatoxin-producing strain in all treatments, suggesting there may be an energetic cost to toxin production. Cellular anatoxin concentrations were lowest (169 fg cell(-1)) under the high-nitrogen and high-phosphorus treatment. This supports the growth-differentiation balance hypothesis that suggests actively dividing and expanding cells are less likely to produce secondary-metabolites. Anatoxin quota was highest (>407 fg cell(-1)) in the reduced phosphorus treatments, possibly suggesting that it is produced as a stress response to growth limiting conditions. In all treatments there was a 4-5-fold increase in anatoxin quota in the lag growth phase, possibly indicating it may provide a physiological benefit during initial substrate colonization. PMID- 26862140 TI - Amoeba-resisting bacteria found in multilamellar bodies secreted by Dictyostelium discoideum: social amoebae can also package bacteria. AB - Many bacteria can resist phagocytic digestion by various protozoa. Some of these bacteria (all human pathogens) are known to be packaged in multilamellar bodies produced in the phagocytic pathway of the protozoa and that are secreted into the extracellular milieu. Packaged bacteria are protected from harsh conditions, and the packaging process is suspected to promote bacterial persistence in the environment. To date, only a limited number of protozoa, belonging to free-living amoebae and ciliates, have been shown to perform bacteria packaging. It is still unknown if social amoebae can do bacteria packaging. The link between the capacity of 136 bacterial isolates to resist the grazing of the social amoeba Dictyostelium discoideum and to be packaged by this amoeba was investigated in the present study. The 45 bacterial isolates displaying a resisting phenotype were tested for their capacity to be packaged. A total of seven isolates from Cupriavidus, Micrococcus, Microbacterium and Rathayibacter genera seemed to be packaged and secreted by D. discoideum based on immunofluorescence results. Electron microscopy confirmed that the Cupriavidus and Rathayibacter isolates were formally packaged. These results show that social amoebae can package some bacteria from the environment revealing a new aspect of microbial ecology. PMID- 26862141 TI - Severe dystrophic calcinosis cutis with tumor-like nodules. PMID- 26862143 TI - Intrinsic characteristics of Min proteins on the cell division of Helicobacter pylori. AB - Helicobacter pylori divides in the human stomach resulting in persistent infections and causing various disorders. Bacterial cell division is precisely coordinated by many molecules, including FtsZ and Min proteins. However, the role of Min proteins in H. pylori division is poorly understood. We investigated the functional characteristics of Min proteins in wild-type HPK5 and five HPK5 derivative mutants using morphological and genetic approaches. All mutants showed a filamentous shape. However, the bacterial cell growth and viability of three single-gene mutants (minC, minD, minE) were similar to that of the wild-type. The coccoid form number was lowest in the minE-disruptant, indicating that MinE contributes to the coccoid form conversion during the stationary phase. Immunofluorescence microscopic observations showed that FtsZ was dispersedly distributed throughout the bacterial cell irrespective of nucleoid position in only minD-disruptants, indicating that MinD is involved in the nucleoid occlusion system. A chase assay demonstrated that MinC loss suppressed FtsZ-degradation, indicating that FtsZ degrades in a MinC-dependent manner. Molecular interactions between FtsZ and Min proteins were confirmed by immunoprecipitation (IP)-western blotting (WB), suggesting the functional cooperation of these molecules during bacterial cell division. This study describes the intrinsic characteristics of Min proteins and provides new insights into H. pylori cell division. PMID- 26862144 TI - CrAgDb--a database of annotated chaperone repertoire in archaeal genomes. AB - Chaperones are a diverse class of ubiquitous proteins that assist other cellular proteins in folding correctly and maintaining their native structure. Many different chaperones cooperate to constitute the 'proteostasis' machinery in the cells. It has been proposed earlier that archaeal organisms could be ideal model systems for deciphering the basic functioning of the 'protein folding machinery' in higher eukaryotes. Several chaperone families have been characterized in archaea over the years but mostly one protein at a time, making it difficult to decipher the composition and mechanistics of the protein folding system as a whole. In order to deal with these lacunae, we have developed a database of all archaeal chaperone proteins, CrAgDb (Chaperone repertoire in Archaeal genomes). The data have been presented in a systematic way with intuitive browse and search facilities for easy retrieval of information. Access to these curated datasets should expedite large-scale analysis of archaeal chaperone networks and significantly advance our understanding of operation and regulation of the protein folding machinery in archaea. Researchers could then translate this knowledge to comprehend the more complex protein folding pathways in eukaryotic systems. The database is freely available at http://14.139.227.92/mkumar/cragdb/. PMID- 26862145 TI - Evaluation of viability, metabolic activity and spore quantity in clostridial cultures during ABE fermentation. AB - Flow cytometry, in combination with fluorescent staining, was used to evaluate population heterogeneity in acetone-butanol-ethanol fermentation that was carried out with type strain Clostridium beijerinckii NCIMB 8052 and non-type C. pasteurianum NRRL B-598. A combination of propidium iodide (PI) and carboxyfluorescein diacetate (CFDA), PI plus Syto-9 and bis-oxonol (BOX) alone were employed to distinguish between active and damaged cells together with simultaneous detection of spores. These strategies provided valuable information on the physiological state of clostridia. CFDA and PI staining gave the best separation of four distinct subpopulations of enzymatically active cells, doubly stained cells, damaged cells and spores. Proportional representation of cells in particular sub-regions correlated with growth characteristics, fermentation parameters such as substrate consumption and product formation in both species under different cultivation conditions. PMID- 26862146 TI - Outcomes of Endovascular Therapy With the Controlled Antegrade Retrograde Subintimal Tracking (CART) or Reverse CART Technique for Long Infrainguinal Occlusions. AB - PURPOSE: To compare the safety, efficacy, and clinical outcomes associated with the controlled antegrade retrograde subintimal tracking (CART) or reverse CART (r CART) technique to the conventional retrograde approach in the treatment of patients with long infrainguinal occlusions. METHODS: From May 2008 to April 2014, 121 patients failed antegrade recanalization and underwent a retrograde approach to recanalize long infrainguinal occlusions. Patients who underwent successful endovascular therapy (EVT) by the conventional retrograde approach (CRA group) were compared to patients who had successful EVT using the CART/r CART technique (CART group) after failure of a bidirectional approach. The efficacy, safety, vessel patency, and other clinical outcomes were compared between the groups. RESULTS: Fifty-eight patients (mean age 71.6 +/- 12.2 years; 32 men) underwent successful EVT (47.9%, 58/121) using the conventional retrograde approach (CRA group), while 44 patients (mean age 70.8 +/- 11.1 years; 31 men) among the 50 patients who underwent the CART/r-CART technique were successfully treated (88.0%, 44/50). Both groups had similar average occlusion lengths and gained 100% immediate hemodynamic success after EVT. There was no significant difference between the groups regarding procedure-related complications. During follow-up, 28 patients died (p=0.380), but there were no differences in the rates of major (p=0.279) or minor amputation (p=0.417) between the groups. There was no difference in the 2-year primary patency (31% vs 24%, p=0.686), assisted primary patency (66% vs 76%, p=0.251), target vessel revascularization (65% vs 54%, p=0.845), or sustained clinical success (52% vs 46%, p=0.995) rates between the CRA and CART groups, respectively. CONCLUSION: Based on acceptable safety, efficacy, and follow-up results in this study, the CART/r-CART technique can salvage patients with long peripheral occlusions after failure of the conventional antegrade or retrograde approach. PMID- 26862147 TI - Anaerobic co-digestion plants for the revaluation of agricultural waste: Sustainable location sites from a GIS analysis. AB - The aim of this study was to establish sustainably feasible areas for the implementation of anaerobic co-digestion plants for agricultural wastes (cattle/swine slurries and cereal crop wastes). The methodology was based on the use of geographic information systems (GIS), the analytic hierarchy process (AHP) and map algebra generated from hedges related to environmental, social and economic constraints. The GIS model obtained was applied to a region of Chile (Bio Bio Region) as a case study showing the energy potential (205 MW-h) of agricultural wastes (swine/cattle manures and cereal crop wastes) and thereby assessing its energy contribution (3.5%) at country level (Chile). From this model, it was possible to spatially identify the influence of each factor (environmental, economic and social) when defining suitable areas for the siting of anaerobic co-digestion plants. In conclusion, GIS-based models establish appropriate areas for the location of anaerobic co-digestion plants in the revaluation of agricultural waste from the production of energy through biogas production. PMID- 26862148 TI - Recycling of typical supercapacitor materials. AB - A simple, facile and low-cost method for recycling of supercapacitor materials is proposed. This process aims to recover some fundamental components of a used supercapacitor, namely the electrolyte salt tetraethyl ammonium tetrafluoroborate (TEABF4) dissolved in an aprotic organic solvent such as acetonitrile (ACN), the carbonaceous material (activated charcoal, carbon nanotubes) purified, the current collector (aluminium foil) and the separator (paper) for further utilization. The method includes mechanical shredding of the supercapacitor in order to reduce its size, and separation of aluminium foil and paper from the carbonaceous resources containing TEABF4 by sieving. The extraction of TEABF4 from the carbonaceous material was based on its solubility in water and subsequent separation through filtering and distillation. A cyclic voltammetry curve of the recycled carbonaceous material revealed supercapacitor behaviour allowing a potential reutilization. Furthermore, as BF4(-) stemming from TEABF4 can be slowly hydrolysed in an aqueous environment, thus releasing F(-) anions, which are hazardous, we went on to their gradual trapping with calcium acetate and conversion to non-hazardous CaF2. PMID- 26862149 TI - Clinical characterisation of polydactyly in Maine Coon cats. AB - Objectives Polydactyly has been reported in a number of vertebrate species, including the domestic cat. It is a common characteristic in some breeding lines of the Maine Coon. The aim of this study was to assess the limb phenotype of polydactyl cats using physical and radiographic examinations. Methods We used physical examination and radiography to characterise the polydactyly phenotype in a cohort of 70 Maine Coon cats, including 48 polydactyl cats from four different breeding lines from Europe, Canada and the USA. Results The phenotypic expression of polydactyly showed great variability, not only in digit number and conformation, but also in the structure of the carpus and tarsus. Comparison of the size of the radius in polydactyl and non-polydactyl 3-month-old kittens and adult females did not reveal any difference between polydactyl and non-polydactyl cats. Conclusions and relevance We conclude that polydactyly in Maine Coon cats is characterised by broad phenotypic diversity. Polydactyly not only affects digit number and conformation, but also carpus and tarsus conformation, with no apparent deleterious consequence on feline welfare. PMID- 26862151 TI - An innovative capstone health care informatics clinical residency: Interprofessional team collaboration. AB - Integrated information systems and wireless technology have been increasingly incorporated into health care organizations with the premise that information technology will promote safe, high-quality, cost-effective patient care. With the advancement of technology, the level of expertise necessary to assume health care information technology roles has escalated. The purpose of this article is to describe a clinical residency project whereby students in a graduate degree health care informatics program successfully fulfilled program competencies through a faculty-lead research project focused on the use of home telehealth with a group of heart failure patients. Through the use of Donabedian's framework of structure, process, and outcomes, the health care informatics students completed essential learning activities deemed essential for transition into the role of an informatics specialist. Health care informatics educational leaders are encouraged to adapt this template of applied learning into their practices. PMID- 26862150 TI - The Association Between Diabetes and Dementia Among Elderly Individuals: A Nationwide Inpatient Sample Analysis. AB - BACKGROUND/AIM: To date, few studies have cross-examined the relationship between diabetes mellitus (DM) and dementia nationally. There is also a lack of evidence regarding dementia subtypes and how this relationship changes among older individuals. The objective was to better delineate this relationship and influence of multiple comorbidities using a nationwide sample. METHODS: Data were obtained from the Nationwide Inpatient Sample 1998 to 2011 using appropriate International Classification of Diseases, Ninth Version codes. Descriptive and bivariate analysis was performed. Multivariate nominal logistic regression models adjusted for age, sex, race, and comorbidities explored the independent relationship between Alzheimer dementia (AD), non-Alzheimer dementia (VaD), and diabetes. RESULTS: 21% of the participants were diabetic patients, 3.7% had AD, and 2.2% had VaD. Diabetes prevalence in AD, VaD, and no dementia groups were 20.6%, 24.3%, and 26.2%, respectively. In the unadjusted model, those with DM had lower odds of AD (odds ratio [OR] 0.73; 95% confidence interval [CI] 0.72-0.74) and VaD (OR 0.91, 95% CI 0.89-0.92). Adjusting for age, sex, race, and comorbidities, diabetic patients had significantly higher odds of VaD (OR = 1.10, 95% CI 1.08-1.11) and lower odds of AD (OR 0.87, 95% CI 0.86-0.88). Inclusion of interaction terms (age, race/ethnicity, depression, stroke, and hypertension) made the relationship between diabetes and VaD not significant (OR 1.002, 95% CI 0.97-1.03), but the relationship of DM with AD remained significant (OR 0.57, 95% CI 0.56-0.58; P < .05). CONCLUSION: Patients with a diagnosis of diabetes mellitus had lower odds of having AD. Age, race/ethnicity, depression, stroke, and hypertension modified the relationship between DM and both VaD and AD. Further exploration of the relationship between DM and AD is warranted. PMID- 26862153 TI - H2O2 and ABA signaling are responsible for the increased Na+ efflux and water uptake in Gossypium hirsutum L. roots in the non-saline side under non-uniform root zone salinity. AB - Non-uniform root salinity increases the Na(+)efflux, water use, and growth of the root in non-saline side, which may be regulated by some form of signaling induced by the high-salinity side. However, the signaling and its specific function have remained unknown. Using a split-root system to simulate a non-uniform root zone salinity in Gossypium hirsutum L., we showed that the up-regulated expression of sodium efflux-related genes (SOS1, SOS2, PMA1, and PMA2) and water uptake-related genes (PIP1 and PIP2) was possibly involved in the elevated Na(+) efflux and water use in the the roots in the non-saline side. The increased level of indole acetic acid (IAA) in the non-saline side was the likely cause of the increased root growth. Also, the abscisic acid (ABA) and H2O2 contents in roots in the non saline side increased, possibly due to the increased expression of their key biosynthesis genes, NCED and RBOHC, and the decreased expression of ABA catabolic CYP707A genes. Exogenous ABA added to the non-saline side induced H2O2 generation by up-regulating the RBOHC gene, but this was decreased by exogenous fluridone. Exogenous H2O2 added to the non-saline side reduced the ABA content by down regulating NCED genes, which can be induced by diphenylene iodonium (DPI) treatment in the non-saline side, suggesting a feedback mechanism between ABA and H2O2.Both exogenous ABA and H2O2 enhanced the expression of SOS1, PIP1;7 ,PIP2;2, and PIP2;10 genes, but these were down-regulated by fluridone and DPI, suggesting that H2O2 and ABA are important signals for increasing root Na(+) efflux and water uptake in the roots in the non-saline side. PMID- 26862154 TI - Carbon isotope discrimination as a diagnostic tool for C4 photosynthesis in C3-C4 intermediate species. AB - The presence and activity of the C4 cycle in C3-C4 intermediate species have proven difficult to analyze, especially when such activity is low. This study proposes a strategy to detect C4 activity and estimate its contribution to overall photosynthesis in intermediate plants, by using tunable diode laser absorption spectroscopy (TDLAS) coupled to gas exchange systems to simultaneously measure the CO2 responses of CO2 assimilation (A) and carbon isotope discrimination (Delta) under low O2 partial pressure. Mathematical models of C3 C4 photosynthesis and Delta are then fitted concurrently to both responses using the same set of constants. This strategy was applied to the intermediate species Flaveria floridana and F. brownii, and to F. pringlei and F. bidentis as C3 and C4 controls, respectively. Our results support the presence of a functional C4 cycle in F. floridana, that can fix 12-21% of carbon. In F. brownii, 75-100% of carbon is fixed via the C4 cycle, and the contribution of mesophyll Rubisco to overall carbon assimilation increases with CO2 partial pressure in both intermediate plants. Combined gas exchange and Delta measurement and modeling is a powerful diagnostic tool for C4 photosynthesis. PMID- 26862155 TI - Multiple apolipoprotein kinetics measured in human HDL by high resolution/accurate mass parallel reaction monitoring. AB - Endogenous labeling with stable isotopes is used to study the metabolism of proteins in vivo. However, traditional detection methods such as GC/MS cannot measure tracer enrichment in multiple proteins simultaneously, and multiple reaction monitoring MS cannot measure precisely the low tracer enrichment in slowly turning-over proteins as in HDL. We exploited the versatility of the high resolution/accurate mass (HR/AM) quadrupole Orbitrap for proteomic analysis of five HDL sizes. We identified 58 proteins in HDL that were shared among three humans and that were organized into five subproteomes according to HDL size. For seven of these proteins, apoA-I, apoA-II, apoA-IV, apoC-III, apoD, apoE, and apoM, we performed parallel reaction monitoring (PRM) to measure trideuterated leucine tracer enrichment between 0.03 to 1.0% in vivo, as required to study their metabolism. The results were suitable for multicompartmental modeling in all except apoD. These apolipoproteins in each HDL size mainly originated directly from the source compartment, presumably the liver and intestine. Flux of apolipoproteins from smaller to larger HDL or the reverse contributed only slightly to apolipoprotein metabolism. These novel findings on HDL apolipoprotein metabolism demonstrate the analytical breadth and scope of the HR/AM-PRM technology to perform metabolic research. PMID- 26862156 TI - MuRF1 mono-ubiquitinates TRalpha to inhibit T3-induced cardiac hypertrophy in vivo. AB - Thyroid hormone (TH) is recognized for its role in cellular metabolism and growth and participates in homeostasis of the heart. T3 activates pro-survival pathways including Akt and mTOR. Treatment with T3 after myocardial infarction is cardioprotective and promotes elements of physiological hypertrophic response after cardiac injury. Although T3 is known to benefit the heart, very little about its regulation at the molecular level has been described to date. The ubiquitin proteasome system (UPS) regulates nuclear hormone receptors such as estrogen, progesterone, androgen, and glucocorticoid receptors by both degradatory and non-degradatory mechanisms. However, how the UPS regulates T3 mediated activity is not well understood. In this study, we aim to determine the role of the muscle-specific ubiquitin ligase muscle ring finger-1 (MuRF1) in regulating T3-induced cardiomyocyte growth. An increase in MuRF1 expression inhibits T3-induced physiological cardiac hypertrophy, whereas a decrease in MuRF1 expression enhances T3's activity both in vitro and in cardiomyocytes in vivo MuRF1 interacts directly with TRalpha to inhibit its activity by posttranslational ubiquitination in a non-canonical manner. We then demonstrated that a nuclear localization apparatus that regulates/inhibits nuclear receptors by sequestering them within a subcompartment of the nucleus was necessary for MuRF1 to inhibit T3 activity. This work implicates a novel mechanism that enhances the beneficial T3 activity specifically within the heart, thereby offering a potential target to enhance cardiac T3 activity in an organ-specific manner. PMID- 26862158 TI - Opinion: Why protect nature? Rethinking values and the environment. PMID- 26862160 TI - Introducing New Purpose, Aims, and Scope. PMID- 26862162 TI - Retrospective Cyberbullying and Suicide Ideation: The Mediating Roles of Depressive Symptoms, Perceived Burdensomeness, and Thwarted Belongingness. AB - Research suggests that being cyberbullied is associated with increased risk for suicide ideation; however, few studies have examined the underlying mechanisms of this relation, and fewer have examined this relation within a theory of suicide. Specifically, the interpersonal theory of suicide posits that thwarted belongingness (indicated by loneliness and a lack of reciprocal caring relationships) and perceived burdensomeness (indicated by feelings of liability and self-hatred) increase risk for suicide ideation. The current study aimed to examine depressive symptoms, thwarted belongingness, and perceived burdensomeness as mediators between intensity of being cyberbullied and suicide ideation. Participants were college students ( N = 348) who completed assessments of retrospective peer victimization, thwarted interpersonal needs (i.e., thwarted belongingness and perceived burdensomeness), and suicide ideation. The results indicated that after adjusting for sexual orientation, depressive symptoms significantly mediated the relation between intensity of being cyberbullied and suicide ideation. Furthermore, depressive symptoms and perceived burdensomeness serially mediated the relation between intensity of being cyberbullied and suicide ideation; however, thwarted belongingness was not a significant mediator. Clinical and research implications, limitations, and future directions are discussed. PMID- 26862157 TI - Genetic spectrum of Saudi Arabian patients with antenatal cystic kidney disease and ciliopathy phenotypes using a targeted renal gene panel. AB - BACKGROUND: Inherited cystic kidney disorders are a common cause of end-stage renal disease. Over 50 ciliopathy genes, which encode proteins that influence the structure and function of the primary cilia, are implicated in cystic kidney disease. METHODS: To define the phenotype and genotype of cystic kidney disease in fetuses and neonates, we correlated antenatal ultrasound examination and postnatal renal ultrasound examination with targeted exon sequencing, using a renal gene panel. A cohort of 44 families in whom antenatal renal ultrasound scanning findings in affected cases included bilateral cystic kidney disease, echogenic kidneys or enlarged kidneys was investigated. RESULTS: In this cohort, disease phenotypes were severe with 36 cases of stillbirth or perinatal death. Extra renal malformations, including encephalocele, polydactyly and heart malformations, consistent with ciliopathy phenotypes, were frequently detected. Renal gene panel testing identified causative mutations in 21 out of 34 families (62%), where patient and parental DNA was available. In the remaining 10 families, where only parental DNA was available, 7 inferred causative mutations were found. Together, mutations were found in 12 different genes with a total of 13 novel pathogenic variants, including an inferred novel variant in NEK8. Mutations in CC2D2A were the most common cause of an antenatal cystic kidney disease and a suspected ciliopathy in our cohort. CONCLUSIONS: In families with ciliopathy phenotypes, mutational analysis using a targeted renal gene panel allows a rapid molecular diagnosis and provides important information for patients, parents and their physicians. PMID- 26862163 TI - Looking back to move forward: Reflections and projections on Journal of Intellectual Disabilities. PMID- 26862165 TI - Pitfalls reconstructing the last common ancestor of chimpanzees and humans. PMID- 26862164 TI - Reply to Almecija: A new direction for reconstructing our last common ancestor with chimpanzees. PMID- 26862166 TI - Reservoir expansion by T-cell proliferation may be another barrier to curing HIV infection. PMID- 26862167 TI - Antigen clasping by two antigen-binding sites of an exceptionally specific antibody for histone methylation. AB - Antibodies have a well-established modular architecture wherein the antigen binding site residing in the antigen-binding fragment (Fab or Fv) is an autonomous and complete unit for antigen recognition. Here, we describe antibodies departing from this paradigm. We developed recombinant antibodies to trimethylated lysine residues on histone H3, important epigenetic marks and challenging targets for molecular recognition. Quantitative characterization demonstrated their exquisite specificity and high affinity, and they performed well in common epigenetics applications. Surprisingly, crystal structures and biophysical analyses revealed that two antigen-binding sites of these antibodies form a head-to-head dimer and cooperatively recognize the antigen in the dimer interface. This "antigen clasping" produced an expansive interface where trimethylated Lys bound to an unusually extensive aromatic cage in one Fab and the histone N terminus to a pocket in the other, thereby rationalizing the high specificity. A long-neck antibody format with a long linker between the antigen binding module and the Fc region facilitated antigen clasping and achieved both high specificity and high potency. Antigen clasping substantially expands the paradigm of antibody-antigen recognition and suggests a strategy for developing extremely specific antibodies. PMID- 26862168 TI - Endogenous dendritic cells from the tumor microenvironment support T-ALL growth via IGF1R activation. AB - Primary T-cell acute lymphoblastic leukemia (T-ALL) cells require stromal-derived signals to survive. Although many studies have identified cell-intrinsic alterations in signaling pathways that promote T-ALL growth, the identity of endogenous stromal cells and their associated signals in the tumor microenvironment that support T-ALL remains unknown. By examining the thymic tumor microenvironments in multiple murine T-ALL models and primary patient samples, we discovered the emergence of prominent epithelial-free regions, enriched for proliferating tumor cells and dendritic cells (DCs). Systematic evaluation of the functional capacity of tumor-associated stromal cells revealed that myeloid cells, primarily DCs, are necessary and sufficient to support T-ALL survival ex vivo. DCs support T-ALL growth both in primary thymic tumors and at secondary tumor sites. To identify a molecular mechanism by which DCs support T ALL growth, we first performed gene expression profiling, which revealed up regulation of platelet-derived growth factor receptor beta (Pdgfrb) and insulin like growth factor I receptor (Igf1r) on T-ALL cells, with concomitant expression of their ligands by tumor-associated DCs. Both Pdgfrb and Igf1r were activated in ex vivo T-ALL cells, and coculture with tumor-associated, but not normal thymic DCs, sustained IGF1R activation. Furthermore, IGF1R signaling was necessary for DC-mediated T-ALL survival. Collectively, these studies provide the first evidence that endogenous tumor-associated DCs supply signals driving T-ALL growth, and implicate tumor-associated DCs and their mitogenic signals as auspicious therapeutic targets. PMID- 26862171 TI - Charles Duncan Michener, 1918-2015. PMID- 26862169 TI - Anoctamin 2 identified as an autoimmune target in multiple sclerosis. AB - Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system and also is regarded as an autoimmune condition. However, the antigenic targets of the autoimmune response in MS have not yet been deciphered. In an effort to mine the autoantibody repertoire within MS, we profiled 2,169 plasma samples from MS cases and population-based controls using bead arrays built with 384 human protein fragments selected from an initial screening with 11,520 antigens. Our data revealed prominently increased autoantibody reactivity against the chloride-channel protein anoctamin 2 (ANO2) in MS cases compared with controls. This finding was corroborated in independent assays with alternative protein constructs and by epitope mapping with peptides covering the identified region of ANO2. Additionally, we found a strong interaction between the presence of ANO2 autoantibodies and the HLA complex MS associated DRB1*15 allele, reinforcing a potential role for ANO2 autoreactivity in MS etiopathogenesis. Furthermore, immunofluorescence analysis in human MS brain tissue showed ANO2 expression as small cellular aggregates near and inside MS lesions. Thus this study represents one of the largest efforts to characterize the autoantibody repertoire within MS. The findings presented here demonstrate that an ANO2 autoimmune subphenotype may exist in MS and lay the groundwork for further studies focusing on the pathogenic role of ANO2 autoantibodies in MS. PMID- 26862170 TI - REDUCED CHLOROPLAST COVERAGE genes from Arabidopsis thaliana help to establish the size of the chloroplast compartment. AB - Eukaryotic cells require mechanisms to establish the proportion of cellular volume devoted to particular organelles. These mechanisms are poorly understood. From a screen for plastid-to-nucleus signaling mutants in Arabidopsis thaliana, we cloned a mutant allele of a gene that encodes a protein of unknown function that is homologous to two other Arabidopsis genes of unknown function and to FRIENDLY, which was previously shown to promote the normal distribution of mitochondria in Arabidopsis. In contrast to FRIENDLY, these three homologs of FRIENDLY are found only in photosynthetic organisms. Based on these data, we proposed that FRIENDLY expanded into a small gene family to help regulate the energy metabolism of cells that contain both mitochondria and chloroplasts. Indeed, we found that knocking out these genes caused a number of chloroplast phenotypes, including a reduction in the proportion of cellular volume devoted to chloroplasts to 50% of wild type. Thus, we refer to these genes as REDUCED CHLOROPLAST COVERAGE (REC). The size of the chloroplast compartment was reduced most in rec1 mutants. The REC1 protein accumulated in the cytosol and the nucleus. REC1 was excluded from the nucleus when plants were treated with amitrole, which inhibits cell expansion and chloroplast function. We conclude that REC1 is an extraplastidic protein that helps to establish the size of the chloroplast compartment, and that signals derived from cell expansion or chloroplasts may regulate REC1. PMID- 26862172 TI - Lasing in robust cesium lead halide perovskite nanowires. AB - The rapidly growing field of nanoscale lasers can be advanced through the discovery of new, tunable light sources. The emission wavelength tunability demonstrated in perovskite materials is an attractive property for nanoscale lasers. Whereas organic-inorganic lead halide perovskite materials are known for their instability, cesium lead halides offer a robust alternative without sacrificing emission tunability or ease of synthesis. Here, we report the low temperature, solution-phase growth of cesium lead halide nanowires exhibiting low threshold lasing and high stability. The as-grown nanowires are single crystalline with well-formed facets, and act as high-quality laser cavities. The nanowires display excellent stability while stored and handled under ambient conditions over the course of weeks. Upon optical excitation, Fabry-Perot lasing occurs in CsPbBr3 nanowires with an onset of 5 MUJ cm(-2) with the nanowire cavity displaying a maximum quality factor of 1,009 +/- 5. Lasing under constant, pulsed excitation can be maintained for over 1 h, the equivalent of 10(9) excitation cycles, and lasing persists upon exposure to ambient atmosphere. Wavelength tunability in the green and blue regions of the spectrum in conjunction with excellent stability makes these nanowire lasers attractive for device fabrication. PMID- 26862174 TI - Unpacking the origins of in-cell crowding. PMID- 26862173 TI - Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins. AB - Mitochondria are major suppliers of cellular energy through nutrients oxidation. Little is known about the mechanisms that enable mitochondria to cope with changes in nutrient supply and energy demand that naturally occur throughout the day. To address this question, we applied MS-based quantitative proteomics on isolated mitochondria from mice killed throughout the day and identified extensive oscillations in the mitochondrial proteome. Remarkably, the majority of cycling mitochondrial proteins peaked during the early light phase. We found that rate-limiting mitochondrial enzymes that process lipids and carbohydrates accumulate in a diurnal manner and are dependent on the clock proteins PER1/2. In this conjuncture, we uncovered daily oscillations in mitochondrial respiration that peak during different times of the day in response to different nutrients. Notably, the diurnal regulation of mitochondrial respiration was blunted in mice lacking PER1/2 or on a high-fat diet. We propose that PERIOD proteins optimize mitochondrial metabolism to daily changes in energy supply/demand and thereby, serve as a rheostat for mitochondrial nutrient utilization. PMID- 26862176 TI - Reply to Halanych et al.: Ctenophore misplacement is corroborated by independent datasets. PMID- 26862175 TI - T cell-intrinsic S1PR1 regulates endogenous effector T-cell egress dynamics from lymph nodes during infection. AB - Viral clearance requires effector T-cell egress from the draining lymph node (dLN). The mechanisms that regulate the complex process of effector T-cell egress from the dLN after infection are poorly understood. Here, we visualized endogenous pathogen-specific effector T-cell migration within, and from, the dLN. We used an inducible mouse model with a temporally disrupted sphingosine-1 phosphate receptor-1 (S1PR1) gene specifically in endogenous effector T cells. Early after infection, WT and S1PR1(-/-) effector T cells localized exclusively within the paracortex. This localization in the paracortex by CD8 T cells was followed by intranodal migration by both WT and S1PR1(-/-) T cells to positions adjacent to both cortical and medullary lymphatic sinuses where the T cells exhibited intense probing behavior. However, in contrast to WT, S1PR1(-/-) effector T cells failed to enter the sinuses. We demonstrate that, even when LN retention signals such as CC chemokine receptor 7 (CCR7) are down-regulated, T cell intrinsic S1PR1 is the master regulator of effector T-cell emigration from the dLN. PMID- 26862177 TI - Miscues misplace sponges. PMID- 26862178 TI - The role of distributed education in recruitment and retention of family physicians. AB - BACKGROUND: Distributed medical education (DME) programmes, in which training occurs in underserviced areas, have been established as a strategy to increase recruitment and retention of new physicians following graduation to these areas. Little is known about what makes physicians remain in the area in which they train. OBJECTIVES: To explore the factors that contributed to family physician's decisions to practice in an underserviced area following graduation from a DME programme. METHODS: Semistructured inperson interviews were conducted with 19 family physicians who graduated from a DME residency training programme. Programme records were reviewed to identify practice location of DME programme graduates. RESULTS: Of the 32 graduates to date from this DME programme, 66% (N=21) and all of the interview participants established their practices in this region after completing their residency training. Five key themes were identified from the interview analysis as impacting physicians' decisions to establish their practice in an underserviced area following graduation: familial ties to the region, practice opportunities, positive clerkship and residency experiences, established relationships with specialists and services in the area and lifestyle opportunities afforded by the location. CONCLUSIONS: This study suggests that DME programmes can be an effective strategy for equalising the distribution of family physicians and highlights the ways in which these programmes can facilitate recruitment and retention in underserviced areas, including being responsive to residents' personal preferences and objectives for learning and shaping their residency experiences to meet to these objectives. PMID- 26862180 TI - Polyphosphate and acidocalcisomes. AB - Inorganic polyphosphate (polyP) accumulates in acidocalcisomes, acidic calcium stores that have been found from bacteria to human cells. Proton pumps, such as the vacuolar proton pyrophosphatase (V-H(+)-PPase or VP1), the vacuolar proton ATPase (V-H(+)-ATPase) or both, maintain their acidity. A vacuolar transporter chaperone (VTC) complex is involved in the synthesis and translocation of polyP to these organelles in several eukaryotes, such as yeast, trypanosomatids, Apicomplexan and algae. Studies in trypanosomatids have revealed the role of polyP and acidocalcisomes in osmoregulation and calcium signalling. PMID- 26862181 TI - Inorganic polyphosphate (polyP) as an activator and structural component of the mitochondrial permeability transition pore. AB - Mitochondrial permeability transition pore (mPTP) is a large channel located in the mitochondrial inner membrane. The opening of mPTP during pathological calcium overload leads to the membrane depolarization and disruption of ATP production. mPTP activation has been implicated as a central event during the process of stress-induced cell death. mPTP is a supramolecular complex composed of many proteins. Recent studies suggest that mitochondrial ATPase plays the central role in the formation of mPTP. However, the structure of the central conducting pore part of mPTP (mPTPore) remains elusive. Here we review current models proposed for the mPTPore and involvement of polyP in its formation and regulation. We discuss the underestimated role of polyP as an effector and a putative structural component of the mPTPore. We propose the hypothesis that inclusion of polyP can explain such properties of mPTP activity as calcium activation, selectivity and voltage-dependence. PMID- 26862182 TI - The new world of inorganic polyphosphates. AB - Post-translational modifications (PTMs) add regulatory features to proteins that help establish the complex functional networks that make up higher organisms. Advances in analytical detection methods have led to the identification of more than 200 types of PTMs. However, some modifications are unstable under the present detection methods, anticipating the existence of further modifications and a much more complex map of PTMs. An example is the recently discovered protein modification polyphosphorylation. Polyphosphorylation is mediated by inorganic polyphosphate (polyP) and represents the covalent attachment of this linear polymer of orthophosphate to lysine residues in target proteins. This modification has eluded MS analysis as both polyP itself and the phosphoramidate bonds created upon its reaction with lysine residues are highly unstable in acidic conditions. Polyphosphorylation detection was only possible through extensive biochemical characterization. Two targets have been identified: nuclear signal recognition 1 (Nsr1) and its interacting partner, topoisomerase 1 (Top1). Polyphosphorylation occurs within a conserved N-terminal polyacidic serine (S) and lysine (K) rich (PASK) cluster. It negatively regulates Nsr1-Top1 interaction and impairs Top1 enzymatic activity, namely relaxing supercoiled DNA. Modulation of cellular levels of polyP regulates Top1 activity by modifying its polyphosphorylation status. Here we discuss the significance of the recently identified new role of inorganic polyP. PMID- 26862179 TI - New photosensitizers for photodynamic therapy. AB - Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound. PMID- 26862183 TI - Polyphosphate as a haemostatic modulator. AB - Platelets are small anuclear cells that play a central role in haemostasis. Platelets become activated in response to various stimuli triggering release of their granular contents into the surrounding milieu. One of these types of granules, termed dense granules, have been found to contain polyphosphate (polyP) in addition to other inorganic biomolecules, such as serotonin, ADP, ATP, PPi. Individuals deficient in dense granules exhibit bleeding tendencies, emphasizing their importance in haemostasis. Platelet polyP is of a relatively defined size, approximately 60-100 phosphate monomers in length. These linear polymers act at various points in the coagulation and fibrinolytic systems thereby modulating the haemostatic response. Due to its highly anionic nature, polyP lends itself to being a natural activator of the contact system. The contact system functions in multiple pathways including coagulation, fibrinolysis, inflammation and complement. Activation of the contact system accelerates thrombin generation, the terminal enzyme in the coagulation cascade. PolyP also modulates factors further downstream in the coagulation cascade to augment thrombin generation. The net effect is increased fibrin formation and platelet activation resulting in faster clot formation. PolyP is incorporated into the forming clot thereby modifying the structure of the resulting fibrin network and its susceptibility to degradation by certain plasminogen activators. In conclusion, release of platelet polyP at the site of injury may facilitate clot formation and augment clot stability thereby promoting wound healing. PMID- 26862184 TI - Inorganic polyphosphate in cardiac myocytes: from bioenergetics to the permeability transition pore and cell survival. AB - Inorganic polyphosphate (polyP) is a linear polymer of Pi residues linked together by high-energy phosphoanhydride bonds as in ATP. PolyP is present in all living organisms ranging from bacteria to human and possibly even predating life of this planet. The length of polyP chain can vary from just a few phosphates to several thousand phosphate units long, depending on the organism and the tissue in which it is synthesized. PolyP was extensively studied in prokaryotes and unicellular eukaryotes by Kulaev's group in the Russian Academy of Sciences and by the Nobel Prize Laureate Arthur Kornberg at Stanford University. Recently, we reported that mitochondria of cardiac ventricular myocytes contain significant amounts (280+/-60 pmol/mg of protein) of polyP with an average length of 25 Pi and that polyP is involved in Ca(2+)-dependent activation of the mitochondrial permeability transition pore (mPTP). Enzymatic polyP depletion prevented Ca(2+) induced mPTP opening during ischaemia; however, it did not affect reactive oxygen species (ROS)-mediated mPTP opening during reperfusion and even enhanced cell death in cardiac myocytes. We found that ROS generation was actually enhanced in polyP-depleted cells demonstrating that polyP protects cardiac myocytes against enhanced ROS formation. Furthermore, polyP concentration was dynamically changed during activation of the mitochondrial respiratory chain and stress conditions such as ischaemia/reperfusion (I/R) and heart failure (HF) indicating that polyP is required for the normal heart metabolism. This review discusses the current literature on the roles of polyP in cardiovascular health and disease. PMID- 26862185 TI - Caveats in studies of the physiological role of polyphosphates in coagulation. AB - Platelet-derived polyphosphates (polyP), stored in dense granule and released upon platelet activation, have been claimed to enhance thrombin activation of coagulation factor XI (FXI) and to activate FXII directly. The latter claim is controversial and principal results leading to these conclusions are probably influenced by methodological problems. It is important to consider that low-grade contact activation is initiated by all surfaces and is greatly amplified by the presence of phospholipids simulating the procoagulant membranes of activated platelets. Thus, proper use of inhibitors of the contact pathway and a careful choice of materials for plates and tubes is important to avoid artefacts. The use of phosphatases used to degrade polyP has an important drawback as it also degrades the secondary activators ADP and ATP, which are released from activated platelets. In addition, the use of positively charged inhibitors, such as polymyxin B, to inhibit polyP in platelet-rich plasma and blood is problematic, as polymyxin B also slows coagulation in the absence of polyP. In conclusion we hope awareness of the above caveats may improve research on the physiological roles of polyP in coagulation. PMID- 26862186 TI - Role of inorganic polyphosphate in mammalian cells: from signal transduction and mitochondrial metabolism to cell death. AB - Inorganic polyphosphate (polyP) is a polymer compromised of linearly arranged orthophosphate units that are linked through high-energy phosphoanhydride bonds. The chain length of this polymer varies from five to several thousand orthophosphates. PolyP is distributed in the most of the living organisms and plays multiple functions in mammalian cells, it is important for blood coagulation, cancer, calcium precipitation, immune response and many others. Essential role of polyP is shown for mitochondria, from implication into energy metabolism and mitochondrial calcium handling to activation of permeability transition pore (PTP) and cell death. PolyP is a gliotransmitter which transmits the signal in astrocytes via activation of P2Y1 receptors and stimulation of phospholipase C. PolyP-induced calcium signal in astrocytes can be stimulated by different lengths of this polymer but only long chain polyP induces mitochondrial depolarization by inhibition of respiration and opening of the PTP. It leads to induction of astrocytic cell death which can be prevented by inhibition of PTP with cyclosporine A. Thus, medium- and short-length polyP plays role in signal transduction and mitochondrial metabolism of astrocytes and long chain of this polymer can be toxic for the cells. PMID- 26862187 TI - A cautionary (spectral) tail: red-shifted fluorescence by DAPI-DAPI interactions. AB - The fluorescent dye DAPI is useful for its association with and consequent amplification of an ~460 nm emission maximum upon binding to dsDNA. Labelling with higher DAPI concentrations is a technique used to reveal Pi polymers [polyphosphate (polyP)], with a red-shift to ~520-550 nm fluorescence emission. DAPI-polyP emissions of ~580 nm are also generated upon 415 nm excitation. Red shifted DAPI emission has been associated with polyP and RNA and has more recently been reported with polyadenylic acid (polyA), specific inositol phosphates (IPs) and heparin. We find that amorphous calcium phosphate (ACP) also demonstrates red-shifted DAPI emission at high DAPI concentrations. This DAPI spectral shift has been attributed to DAPI-DAPI electrostatic interactions enabled by molecules with high negative charge density that increase the local DAPI concentration and favour DAPI molecular proximity, as observed by increasing the dye/phosphate ratio. Excitation of dry DAPI (~360 nm) confirmed a red-shifted DAPI emission. Whereas enzymatic approaches to modify substrates can help define the nature of DAPI fluorescence signals, multiple approaches beyond red-shifted DAPI excitation/emission are advised before conclusions are drawn about DAPI substrate identification. PMID- 26862188 TI - The reaction mechanism of retaining glycosyltransferases. AB - The catalytic mechanism of retaining glycosyltransferases (ret-GTs) remains a controversial issue in glycobiology. By analogy to the well-established mechanism of retaining glycosidases, it was first suggested that ret-GTs follow a double displacement mechanism. However, only family 6 GTs exhibit a putative nucleophile protein residue properly located in the active site to participate in catalysis, prompting some authors to suggest an unusual single-displacement mechanism [named as front-face or SNi (substitution nucleophilic internal)-like]. This mechanism has now received strong support, from both experiment and theory, for several GT families except family 6, for which a double-displacement reaction is predicted. In the last few years, we have uncovered the molecular mechanisms of several retaining GTs by means of quantum mechanics/molecular mechanics (QM/MM) metadynamics simulations, which we overview in the present work. PMID- 26862189 TI - Recent structural and mechanistic insights into protein O-GalNAc glycosylation. AB - Protein O-GalNAcylation is an abundant post-translational modification and predicted to occur in over 80% of the proteins passing through the Golgi apparatus. This modification is driven by 20 polypeptide GaINAc (N acetylgalactosamine)-transferases (GalNAc-Ts), which are unique in that they possess both catalytic and lectin domains. The peptide substrate specificities of GalNAc-Ts are still poorly defined and our understanding of the sequence and structural features that direct O-glycosylation of proteins is limited. Part of this may be attributed to the complex regulation by coordinated action of multiple GalNAc-T isoforms, and part of this may also be attributed to the two functional domains of GalNAc-Ts that both seems to be involved in directing the substrate specificities. Recent studies have resulted in 3D structures of GalNAc Ts and determination of the reaction mechanism of this family of enzymes. Key advances include the trapping of binary/ternary complexes in combination with computational simulations and AFM/small-SAXS experiments, which have allowed for the dissection of the reaction coordinates and the mechanism by which the lectin domains modulate the glycosylation. These studies not only broaden our knowledge of the modes-of-action of this family of enzymes but also open up potential avenues for the rational design of effective and selective inhibitors of O glycosylation. PMID- 26862190 TI - alpha-Glucan biosynthesis and the GlgE pathway in Mycobacterium tuberculosis. AB - It has long been reported that Mycobacterium tuberculosis is capable of synthesizing the alpha-glucan glycogen. However, what makes this bacterium stand out is that it coats itself in a capsule that mainly consists of a glycogen-like alpha-glucan. This polymer helps the pathogen evade immune responses. In 2010, the biosynthesis of alpha-glucans has been shown to not only involve the classical enzymes of glycogen metabolism but also a distinct GlgE pathway. Since then, this pathway has attracted attention not least in terms of the quest for new inhibitors that could be developed into new treatments for tuberculosis. Some lines of recent inquiry have shed a lot of light on to how GlgE catalyses the polymerization of alpha-glucan, using alpha-maltose 1-phosphate (M1P) as a building block and how the pathways are regulated. Nevertheless, many unanswered questions remain regarding the synthesis and role of alpha-glucans in mycobacteria and the numerous other bacteria that possess the GlgE pathway. PMID- 26862191 TI - Xylan decoration patterns and the plant secondary cell wall molecular architecture. AB - The molecular architecture of plant secondary cell walls is still not resolved. There are several proposed structures for cellulose fibrils, the main component of plant cell walls and the conformation of other molecules is even less well known. Glucuronic acid (GlcA) substitution of xylan (GUX) enzymes, in CAZy family glycosyl transferase (GT)8, decorate the xylan backbone with various specific patterns of GlcA. It was recently discovered that dicot xylan has a domain with the side chain decorations distributed on every second unit of the backbone (xylose). If the xylan backbone folds in a similar way to glucan chains in cellulose (2-fold helix), this kind of arrangement may allow the undecorated side of the xylan chain to hydrogen bond with the hydrophilic surface of cellulose microfibrils. MD simulations suggest that such interactions are energetically stable. We discuss the possible role of this xylan decoration pattern in building of the plant cell wall. PMID- 26862192 TI - Carbohydrate-active enzymes: sequences, shapes, contortions and cells. AB - The enzyme-catalysed degradation of oligo and polysaccharides is of considerable interest in many fields ranging from the fundamental-understanding the intrinsic chemical beauty-through to the applied, including diverse practical applications in medicine and biotechnology. Carbohydrates are the most stereochemically complex biopolymer, and myriad different natural polysaccharides have led to evolution of multifaceted enzyme consortia for their degradation. The glycosidic bonds that link sugar monomers are among the most chemically-stable, yet enzymatically-labile, bonds in the biosphere. That glycoside hydrolases can achieve a rate enhancement (kcat/kuncat) >10(17)-fold provides testament to their remarkable proficiency and the sophistication of their catalysis reaction mechanisms. The last two decades have seen significant advances in the discovery of new glycosidase sequences, sequence-based classification into families and clans, 3D structures and reaction mechanisms, providing new insights into enzymatic catalysis. New impetus to these studies has been provided by the challenges inherent in plant and microbial polysaccharide degradation, both in the context of environmentally-sustainable routes to foods and biofuels, and increasingly in human nutrition. Study of the reaction mechanism of glycoside hydrolases has also inspired the development of enzyme inhibitors, both as mechanistic probes and increasingly as therapeutic agents. We are on the cusp of a new era where we are learning how to dovetail powerful computational techniques with structural and kinetic data to provide an unprecedented view of conformational details of enzyme action. PMID- 26862193 TI - O-GlcNAc transferase inhibitors: current tools and future challenges. AB - The O-linked N-acetylglucosamine (O-GlcNAc) post-translational modification (O GlcNAcylation) is the dynamic and reversible attachment of N-acetylglucosamine to serine and threonine residues of nucleocytoplasmic target proteins. It is abundant in metazoa, involving hundreds of proteins linked to a plethora of biological functions with implications in human diseases. The process is catalysed by two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) that add and remove sugar moieties respectively. OGT knockout is embryonic lethal in a range of animal models, hampering the study of the biological role of O-GlcNAc and the dissection of catalytic compared with non-catalytic roles of OGT. Therefore, selective and potent chemical tools are necessary to inhibit OGT activity in the context of biological systems. The present review focuses on the available OGT inhibitors and summarizes advantages, limitations and future challenges. PMID- 26862194 TI - Learning from microbial strategies for polysaccharide degradation. AB - Complex carbohydrates are ubiquitous in all kingdoms of life. As major components of the plant cell wall they constitute both a rich renewable carbon source for biotechnological transformation into fuels, chemicals and materials, and also form an important energy source as part of a healthy human diet. In both contexts, there has been significant, sustained interest in understanding how microbes transform these substrates. Classical perspectives of microbial polysaccharide degradation are currently being augmented by recent advances in the discovery of lytic polysaccharide monooxygenases (LPMOs) and polysaccharide utilization loci (PULs). Fundamental discoveries in carbohydrate enzymology are both advancing biological understanding, as well as informing applications in industrial biomass conversion and modulation of the human gut microbiota to mediate health benefits. PMID- 26862195 TI - Sulfatases and radical SAM enzymes: emerging themes in glycosaminoglycan metabolism and the human microbiota. AB - Humans live in a permanent association with bacterial populations collectively called the microbiota. In the last 10 years, major advances in our knowledge of the microbiota have shed light on its critical roles in human physiology. The microbiota has also been shown to be a major factor in numerous pathologies including obesity or inflammatory disorders. Despite tremendous progresses, our understanding of the key functions of the human microbiota and the molecular basis of its interactions with the host remain still poorly understood. Among the factors involved in host colonization, two enzymes families, sulfatases and radical S-adenosyl-L-methionine enzymes, have recently emerged as key enzymes. PMID- 26862196 TI - Galactokinase promiscuity: a question of flexibility? AB - Galactokinase catalyses the first committed step of the Leloir pathway, i.e. the ATP-dependent phosphorylation of alpha-D-galactose at C1-OH. Reduced galactokinase activity results in the inherited metabolic disease type II galactosaemia. However, inhibition of galactokinase is considered a viable approach to treating more severe forms of galactosaemia (types I and III). Considerable progress has been made in the identification of high affinity, selective inhibitors. Although the structure of galactokinase from a variety of species is known, its catalytic mechanism remains uncertain. Although the bulk of evidence suggests that the reaction proceeds via an active site base mechanism, some experimental and theoretical studies contradict this. The enzyme has potential as a biocatalyst in the production of sugar 1-phosphates. This potential is limited by its high specificity. A variety of approaches have been taken to identify galactokinase variants which are more promiscuous. These have broadened galactokinase's specificity to include a wide range of D- and L-sugars. Initial studies suggest that some of these alterations result in increased flexibility at the active site. It is suggested that modulation of protein flexibility is at least as important as structural modifications in determining the success or failure of enzyme engineering. PMID- 26862197 TI - From endolysins to Artilysin(r)s: novel enzyme-based approaches to kill drug resistant bacteria. AB - One of the last untapped reservoirs in nature for the identification of new anti microbials is bacteriophages, the natural killers of bacteria. Lytic bacteriophages encode peptidoglycan (PG) lytic enzymes able to degrade the PG layer in different steps of their infection cycle. Endolysins degrade the bacterial cell wall at the end of the infection cycle, causing lysis of the host to release the viral progeny. Recombinant endolysins have been successfully applied as anti-bacterial agent against antibiotic-resistant Gram-positive pathogens. This has boosted the study of these enzymes as new anti-microbials in different fields (e.g. medical, food technology). A key example is the recent development of endolysin-based anti-bacterials against Gram-negative pathogens in which the exogenous application of endolysins is hindered by the outer membrane (OM). These novel anti-microbials, termed Artilysin(r)s, are able to pass through the OM and reach the PG where they exert their action. In addition, mycobacteria whose cell wall is structurally different from both Gram-positive and Gram negative bacteria have also been reported to be inhibited by mycobacteriophage encoded endolysins. Endolysins and endolysin-based anti-microbials can be considered as ideal candidates for an alternative to antibiotics for several reasons: (1) their unique mode of action and activity against bacterial persisters (independent of an active host metabolism), (2) their selective activity against both Gram-positive and Gram-negative pathogens (including antibiotic resistant strains) and mycobacteria, (3) the limited resistance development reported so far. The present review summarizes and discusses the potential applications of endolysins as new anti-microbials. PMID- 26862199 TI - Discovery and industrial applications of lytic polysaccharide mono-oxygenases. AB - The recent discovery of copper-dependent lytic polysaccharide mono-oxygenases (LPMOs) has opened up a vast area of research covering several fields of application. The biotech company Novozymes A/S holds patents on the use of these enzymes for the conversion of steam-pre-treated plant residues such as straw to free sugars. These patents predate the correct classification of LPMOs and the striking synergistic effect of fungal LPMOs when combined with canonical cellulases was discovered when fractions of fungal secretomes were evaluated in industrially relevant enzyme performance assays. Today, LPMOs are a central component in the Cellic CTec enzyme products which are used in several large scale plants for the industrial production of lignocellulosic ethanol. LPMOs are characterized by an N-terminal histidine residue which, together with an internal histidine and a tyrosine residue, co-ordinates a single copper atom in a so called histidine brace. The mechanism by which oxygen binds to the reduced copper atom has been reported and the general mechanism of copper-oxygen-mediated activation of carbon is being investigated in the light of these discoveries. LPMOs are widespread in both the fungal and the bacterial kingdoms, although the range of action of these enzymes remains to be elucidated. However, based on the high abundance of LPMOs expressed by microbes involved in the decomposition of organic matter, the importance of LPMOs in the natural carbon-cycle is predicted to be significant. In addition, it has been suggested that LPMOs play a role in the pathology of infectious diseases such as cholera and to thus be relevant in the field of medicine. PMID- 26862200 TI - Beta galactosidases in Arabidopsis and tomato - a mini review. AB - Beta galactosidases (BGALs) are glycosyl hydrolases that remove terminal beta-D galactosyl residues from beta-D-galactosides. There are 17 predicted BGAL genes in the genomes of both Arabidopsis (BGAL1-17) and tomato (TBG1-17). All tested BGALs have BGAL activity but their distinct expression profiles and ancient phylogenetic separation indicates that these enzymes fulfil diverse, non redundant roles in plant biology. The majority of these BGALs are predicted to have signal peptide and thought to act during cell wall-related biological processes. Interestingly, deletion of BGAL6 and BGAL10 in Arabidopsis causes reduced mucilage release during seed imbibition and shorter siliques respectively, whereas TBG4 depletion by RNAi decreases in fruit softening in tomato. The majority of plant BGALs remain to be characterized. PMID- 26862198 TI - Glycosyltransferase engineering for carbohydrate synthesis. AB - Glycosyltransferases (GTs) are powerful tools for the synthesis of complex and biologically-important carbohydrates. Wild-type GTs may not have all the properties and functions that are desired for large-scale production of carbohydrates that exist in nature and those with non-natural modifications. With the increasing availability of crystal structures of GTs, especially those in the presence of donor and acceptor analogues, crystal structure-guided rational design has been quite successful in obtaining mutants with desired functionalities. With current limited understanding of the structure-activity relationship of GTs, directed evolution continues to be a useful approach for generating additional mutants with functionality that can be screened for in a high-throughput format. Mutating the amino acid residues constituting or close to the substrate-binding sites of GTs by structure-guided directed evolution (SGDE) further explores the biotechnological potential of GTs that can only be realized through enzyme engineering. This mini-review discusses the progress made towards GT engineering and the lessons learned for future engineering efforts and assay development. PMID- 26862201 TI - Iminosugar inhibitors of carbohydrate-active enzymes that underpin cereal grain germination and endosperm metabolism. AB - Starch is a major energy store in plants. It provides most of the calories in the human diet and, as a bulk commodity, it is used across broad industry sectors. Starch synthesis and degradation are not fully understood, owing to challenging biochemistry at the liquid/solid interface and relatively limited knowledge about the nature and control of starch degradation in plants. Increased societal and commercial demand for enhanced yield and quality in starch crops requires a better understanding of starch metabolism as a whole. Here we review recent advances in understanding the roles of carbohydrate-active enzymes in starch degradation in cereal grains through complementary chemical and molecular genetics. These approaches have allowed us to start dissecting aspects of starch degradation and the interplay with cell-wall polysaccharide hydrolysis during germination. With a view to improving and diversifying the properties and uses of cereal grains, it is possible that starch degradation may be amenable to manipulation through genetic or chemical intervention at the level of cell wall metabolism, rather than simply in the starch degradation pathway per se. PMID- 26862202 TI - Sialidases from gut bacteria: a mini-review. AB - Sialidases are a large group of enzymes, the majority of which catalyses the cleavage of terminal sialic acids from complex carbohydrates on glycoproteins or glycolipids. In the gastrointestinal (GI) tract, sialic acid residues are mostly found in terminal location of mucins via alpha2-3/6 glycosidic linkages. Many enteric commensal and pathogenic bacteria can utilize sialic acids as a nutrient source, but not all express the sialidases that are required to release free sialic acid. Sialidases encoded by gut bacteria vary in terms of their substrate specificity and their enzymatic reaction. Most are hydrolytic sialidases, which release free sialic acid from sialylated substrates. However, there are also examples with transglycosylation activities. Recently, a third class of sialidases, intramolecular trans-sialidase (IT-sialidase), has been discovered in gut microbiota, releasing (2,7-anhydro-Neu5Ac) 2,7-anydro-N-acetylneuraminic acid instead of sialic acid. Reaction specificity varies, with hydrolytic sialidases demonstrating broad activity against alpha2,3-, alpha2,6- and alpha2,8-linked substrates, whereas IT-sialidases tend to be specific for alpha2,3-linked substrates. In this mini-review, we summarize the current knowledge on the structural and biochemical properties of sialidases involved in the interaction between gut bacteria and epithelial surfaces. PMID- 26862204 TI - The amyloid precursor protein (APP) binds the PIKfyve complex and modulates its function. AB - Phosphoinositides are important components of eukaryotic membranes that are required for multiple forms of membrane dynamics. Phosphoinositides are involved in defining membrane identity, mediate cell signalling and control membrane trafficking events. Due to their pivotal role in membrane dynamics, phosphoinositide de-regulation contributes to various human diseases. In this review, we will focus on the newly emerging regulation of the PIKfyve complex, a phosphoinositide kinase that converts the endosomal phosphatidylinositol-3 phosphate [PI(3)P] to phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2)], a low abundance phosphoinositide of outstanding importance for neuronal integrity and function. Loss of PIKfyve function is well known to result in neurodegeneration in both mouse models and human patients. Our recent work has surprisingly identified the amyloid precursor protein (APP), the central molecule in Alzheimer's disease aetiology, as a novel interaction partner of a subunit of the PIKfyve complex, Vac14. Furthermore, it has been shown that APP modulates PIKfyve function and PI(3,5)P2 dynamics, suggesting that the APP gene family functions as regulator of PI(3,5)P2 metabolism. The recent advances discussed in this review suggest a novel, unexpected, beta-amyloid-independent mechanism for neurodegeneration in Alzheimer's disease. PMID- 26862203 TI - Phosphatidylinositol 3,5-bisphosphate: regulation of cellular events in space and time. AB - Phosphorylated phosphatidylinositol lipids are crucial for most eukaryotes and have diverse cellular functions. The low-abundance signalling lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is critical for cellular homoeostasis and adaptation to stimuli. A large complex of proteins that includes the lipid kinase Fab1-PIKfyve, dynamically regulates the levels of PI(3,5)P2. Deficiencies in PI(3,5)P2 are linked to some human diseases, especially those of the nervous system. Future studies will probably determine new, undiscovered regulatory roles of PI(3,5)P2, as well as uncover mechanistic insights into how PI(3,5)P2 contributes to normal human physiology. PMID- 26862206 TI - Phosphatidylinositol and phosphatidic acid transport between the ER and plasma membrane during PLC activation requires the Nir2 protein. AB - Phospholipase C (PLC)-mediated hydrolysis of the limited pool of plasma membrane (PM) phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] requires replenishment from a larger pool of phosphatidylinositol (PtdIns) via sequential phosphorylation by PtdIns 4-kinases and phosphatidylinositol 4-phosphate (PtdIns4P) 5-kinases. Since PtdIns is synthesized in the endoplasmic reticulum (ER) and PtdIns(4,5)P2 is generated in the PM, it has been postulated that PtdIns transfer proteins (PITPs) provide the means for this lipid transfer function. Recent studies identified the large PITP protein, Nir2 as important for PtdIns transfer from the ER to the PM. It was also found that Nir2 was required for the transfer of phosphatidic acid (PtdOH) from the PM to the ER. In Nir2-depleted cells, activation of PLC leads to PtdOH accumulation in the PM and PtdIns synthesis becomes severely impaired. In quiescent cells, Nir2 is localized to the ER via interaction of its FFAT domain with ER-bound VAMP-associated proteins VAP A and-B. After PLC activation, Nir2 also binds to the PM via interaction of its C terminal domains with diacylglycerol (DAG) and PtdOH. Through these interactions, Nir2 functions in ER-PM contact zones. Mutations in VAP-B that have been identified in familial forms of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) cause aggregation of the VAP-B protein, which then impairs its binding to several proteins, including Nir2. These findings have shed new lights on the importance of non-vesicular lipid transfer of PtdIns and PtdOH in ER-PM contact zones with a possible link to a devastating human disease. PMID- 26862205 TI - Towards pharmacological intervention in inositol pyrophosphate signalling. AB - To help define the molecular basis of cellular signalling cascades, and their biological functions, there is considerable value in utilizing a high-quality chemical 'probe' that has a well-defined interaction with a specific cellular protein. Such reagents include inhibitors of protein kinases and small molecule kinases, as well as mimics or antagonists of intracellular signals. The purpose of this review is to consider recent progress and promising future directions for the development of novel molecules that can interrogate and manipulate the cellular actions of inositol pyrophosphates (PP-IPs)--a specialized, 'energetic' group of cell-signalling molecules in which multiple phosphate and diphosphate groups are crammed around a cyclohexane polyol scaffold. PMID- 26862207 TI - A tale of two inositol trisphosphates. AB - Between spring 1982 and autumn 1984 the physiological role of Ins(1,4,5)P3 as a calcium-mobilizing second messenger was first suggested and then experimentally established. At the same time the unexpected complexity of inositide metabolism began to be exposed by the discovery of Ins(1,3,4)P3. This article recalls my entanglement with these two inositol phosphates. PMID- 26862209 TI - Does PtdIns(4,5)P2 concentrate so it can multi-task? AB - Ptdns(4,5)P2 is a minor structural lipid of the plasma membrane (PM), but a master regulator of PM function. Serving either as a substrate for the generation of second messengers, or more commonly as a ligand triggering protein recruitment or activation, it regulates most aspects of PM function. Understanding how this relatively simple biological macromolecule can regulate such a vast array of different functions in parallel, is the key to understanding the biology of the PM as a whole, in both health and disease. In this review, potential mechanisms are discussed that might explain how a lipid can separately regulate so many protein complexes. The focus is on the spatial distribution of the lipid molecules, their metabolism and their interactions. Open questions that still need to be resolved are highlighted, as are potential experimental approaches that might shed light on the mechanisms at play. Moreover, the broader question is raised as to whether PtdIns(4,5)P2 should be thought of as a bona fide signalling molecule or more of a simple lipid cofactor or perhaps both, depending on the context of the particular function in question. PMID- 26862210 TI - Enzymes of yeast polyphosphate metabolism: structure, enzymology and biological roles. AB - Inorganic polyphosphate (polyP) is found in all living organisms. The known polyP functions in eukaryotes range from osmoregulation and virulence in parasitic protozoa to modulating blood coagulation, inflammation, bone mineralization and cellular signalling in mammals. However mechanisms of regulation and even the identity of involved proteins in many cases remain obscure. Most of the insights obtained so far stem from studies in the yeast Saccharomyces cerevisiae. Here, we provide a short overview of the properties and functions of known yeast polyP metabolism enzymes and discuss future directions for polyP research. PMID- 26862211 TI - Regulation of PtdIns(3,4,5)P3/Akt signalling by inositol polyphosphate 5 phosphatases. AB - The phosphoinositide 3-kinase (PI3K) generated lipid signals, PtdIns(3,4,5)P3 and PtdIns(3,4)P2, are both required for the maximal activation of the serine/threonine kinase proto-oncogene Akt. The inositol polyphosphate 5 phosphatases (5-phosphatases) hydrolyse the 5-position phosphate from the inositol head group of PtdIns(3,4,5)P3 to yield PtdIns(3,4)P2. Extensive work has revealed several 5-phosphatases inhibit PI3K-driven Akt signalling, by decreasing PtdIns(3,4,5)P3 despite increasing cellular levels of PtdIns(3,4)P2. The roles that 5-phosphatases play in suppressing cell proliferation and transformation are slow to emerge; however, the 5-phosphatase PIPP [proline-rich inositol polyphosphate 5-phosphatase; inositol polyphosphate 5-phosphatase (INPP5J)] has recently been identified as a putative tumour suppressor in melanoma and breast cancer and SHIP1 [SH2 (Src homology 2)-containing inositol phosphatase 1] inhibits haematopoietic cell proliferation. INPP5E regulates cilia stability and INPP5E mutations have been implicated ciliopathy syndromes. This review will examine 5-phosphatase regulation of PI3K/Akt signalling, focussing on the role PtdIns(3,4,5)P3 5-phosphatases play in developmental diseases and cancer. PMID- 26862212 TI - Phosphate, inositol and polyphosphates. AB - Eukaryotic cells have ubiquitously utilized the myo-inositol backbone to generate a diverse array of signalling molecules. This is achieved by arranging phosphate groups around the six-carbon inositol ring. There is virtually no biological process that does not take advantage of the uniquely variable architecture of phosphorylated inositol. In inositol biology, phosphates are able to form three distinct covalent bonds: phosphoester, phosphodiester and phosphoanhydride bonds, with each providing different properties. The phosphoester bond links phosphate groups to the inositol ring, the variable arrangement of which forms the basis of the signalling capacity of the inositol phosphates. Phosphate groups can also form the structural bridge between myo-inositol and diacylglycerol through the phosphodiester bond. The resulting lipid-bound inositol phosphates, or phosphoinositides, further expand the signalling potential of this family of molecules. Finally, inositol is also notable for its ability to host more phosphates than it has carbons. These unusual organic molecules are commonly referred to as the inositol pyrophosphates (PP-IPs), due to the presence of high energy phosphoanhydride bonds (pyro- or diphospho-). PP-IPs themselves constitute a varied family of molecules with one or more pyrophosphate moiety/ies located around the inositol. Considering the relationship between phosphate and inositol, it is no surprise that members of the inositol phosphate family also regulate cellular phosphate homoeostasis. Notably, the PP-IPs play a fundamental role in controlling the metabolism of the ancient polymeric form of phosphate, inorganic polyphosphate (polyP). Here we explore the intimate links between phosphate, inositol phosphates and polyP, speculating on the evolution of these relationships. PMID- 26862213 TI - Type III phosphatidylinositol 4 kinases: structure, function, regulation, signalling and involvement in disease. AB - Many important cellular functions are regulated by the selective recruitment of proteins to intracellular membranes mediated by specific interactions with lipid phosphoinositides. The enzymes that generate lipid phosphoinositides therefore must be properly positioned and regulated at their correct cellular locations. Phosphatidylinositol 4 kinases (PI4Ks) are key lipid signalling enzymes, and they generate the lipid species phosphatidylinositol 4-phosphate (PI4P), which plays important roles in regulating physiological processes including membrane trafficking, cytokinesis and organelle identity. PI4P also acts as the substrate for the generation of the signalling phosphoinositides phosphatidylinositol 4,5 bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). PI4Ks also play critical roles in a number of pathological processes including mediating replication of a number of pathogenic RNA viruses, and in the development of the parasite responsible for malaria. Key to the regulation of PI4Ks is their regulation by a variety of both host and viral protein-binding partners. We review herein our current understanding of the structure, regulatory interactions and role in disease of the type III PI4Ks. PMID- 26862208 TI - Specificity and disease in the ubiquitin system. AB - Post-translational modification (PTM) of proteins by ubiquitination is an essential cellular regulatory process. Such regulation drives the cell cycle and cell division, signalling and secretory pathways, DNA replication and repair processes and protein quality control and degradation pathways. A huge range of ubiquitin signals can be generated depending on the specificity and catalytic activity of the enzymes required for attachment of ubiquitin to a given target. As a consequence of its importance to eukaryotic life, dysfunction in the ubiquitin system leads to many disease states, including cancers and neurodegeneration. This review takes a retrospective look at our progress in understanding the molecular mechanisms that govern the specificity of ubiquitin conjugation. PMID- 26862214 TI - The sperm phospholipase C-zeta and Ca2+ signalling at fertilization in mammals. AB - A series of intracellular oscillations in the free cytosolic Ca(2+) concentration is responsible for activating mammalian eggs at fertilization, thus initiating embryo development. It has been proposed that the sperm causes these Ca(2+) oscillations after membrane fusion by delivering a soluble protein into the egg cytoplasm. We previously identified sperm-specific phospholipase C (PLC)-zeta as a protein that can trigger the same pattern of Ca(2+) oscillations in eggs seen at fertilization. PLCzeta appears to be the elusive sperm factor mediating egg activation in mammals. It has potential therapeutic use in infertility treatments to improve the rate of egg activation and early embryo development after intra cytoplasmic sperm injection. A stable form of recombinant human PLCzeta could be a prototype for use in such in vitro fertilization (IVF) treatments. We do not yet understand exactly how PLCzeta causes inositol 1,4,5-trisphosphate (InsP3) production in eggs. Sperm PLCzeta is distinct among mammalian PI-specific PLCs in that it is far more potent in triggering Ca(2+) oscillations in eggs than other PLCs, but it lacks a PH domain that would otherwise be considered essential for binding to the phosphatidylinositol 4,5-bisphosphate (PIP2) substrate. PLCzeta is also unusual in that it does not appear to interact with or hydrolyse plasma membrane PIP2. We consider how other regions of PLCzeta may mediate its binding to PIP2 in eggs and how interaction of PLCzeta with egg-specific factors could enable the hydrolysis of internal sources of PIP2. PMID- 26862215 TI - The PTEN protein: cellular localization and post-translational regulation. AB - The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) phosphatase dephosphorylates PIP3, the lipid product of the class I PI 3-kinases, and suppresses the growth and proliferation of many cell types. It has been heavily studied, in large part due to its status as a tumour suppressor, the loss of function of which is observed through diverse mechanisms in many tumour types. Here we present a concise review of our understanding of the PTEN protein and highlight recent advances, particularly in our understanding of its localization and regulation by ubiquitination and SUMOylation. PMID- 26862216 TI - Inositol polyphosphate multikinase (IPMK) in transcriptional regulation and nuclear inositide metabolism. AB - Inositol polyphosphate multikinase (IPMK, ipk2, Arg(82), ArgRIII) is an inositide kinase with unusually flexible substrate specificity and the capacity to partake in many functional protein-protein interactions (PPIs). By merging these two activities, IPMK is able to execute gene regulatory functions that are very unique and only now beginning to be recognized. In this short review, we present a brief history of IPMK, describe the structural biology of the enzyme and highlight a few recent discoveries that have shed more light on the role IPMK plays in inositide metabolism, nuclear signalling and transcriptional regulation. PMID- 26862217 TI - RdgBalpha reciprocally transfers PA and PI at ER-PM contact sites to maintain PI(4,5)P2 homoeostasis during phospholipase C signalling in Drosophila photoreceptors. AB - Phosphatidylinositol (PI) is the precursor lipid for the synthesis of PI 4,5 bisphosphate [PI(4,5)P2] at the plasma membrane (PM) and is sequentially phosphorylated by the lipid kinases, PI 4-kinase and phosphatidylinositol 4 phosphate (PI4P)-5-kinase. Receptor-mediated hydrolysis of PI(4,5)P2 takes place at the PM but PI resynthesis occurs at the endoplasmic reticulum (ER). Thus PI(4,5)P2 resynthesis requires the reciprocal transport of two key intermediates, phosphatidic acid (PA) and PI between the ER and the PM. PI transfer proteins (PITPs), defined by the presence of the PITP domain, can facilitate lipid transfer between membranes; the PITP domain comprises a hydrophobic cavity with dual specificity but accommodates a single phospholipid molecule. The class II PITP, retinal degeneration type B (RdgB)alpha is a multi-domain protein and its PITP domain can bind and transfer PI and PA. In Drosophila photoreceptors, a well defined G-protein-coupled phospholipase Cbeta (PLCbeta) signalling pathway, phototransduction defects resulting from loss of RdgBalpha can be rescued by expression of the PITP domain provided it is competent for both PI and PA transfer. We propose that RdgBalpha proteins maintain PI(4,5)P2 homoeostasis after PLC activation by facilitating the reciprocal transport of PA and PI at ER PM membrane contact sites. PMID- 26862218 TI - Phosphoinositide signalling in type 2 diabetes: a beta-cell perspective. AB - Type 2 diabetes is a complex disease. It results from a failure of the body to maintain energy homoeostasis. Multicellular organisms have evolved complex strategies to preserve a relatively stable internal nutrient environment, despite fluctuations in external nutrient availability. This complex strategy involves the co-ordinated responses of multiple organs to promote storage or mobilization of energy sources according to the availability of nutrients and cellular bioenergetics needs. The endocrine pancreas plays a central role in these processes by secreting insulin and glucagon. When this co-ordinated effort fails, hyperglycaemia and hyperlipidaemia develops, characterizing a state of metabolic imbalance and ultimately overt diabetes. Although diabetes is most likely a collection of diseases, scientists are starting to identify genetic components and environmental triggers. Genome-wide association studies revealed that by and large, gene variants associated with type 2 diabetes are implicated in pancreatic beta-cell function, suggesting that the beta-cell may be the weakest link in the chain of events that results in diabetes. Thus, it is critical to understand how environmental cues affect the beta-cell. Phosphoinositides are important 'decoders' of environmental cues. As such, these lipids have been implicated in cellular responses to a wide range of growth factors, hormones, stress agents, nutrients and metabolites. Here we will review some of the well-established and potential new roles for phosphoinositides in beta-cell function/dysfunction and discuss how our knowledge of phosphoinositide signalling could aid in the identification of potential strategies for treating or preventing type 2 diabetes. PMID- 26862219 TI - Phosphoinositides in the nucleus and myogenic differentiation: how a nuclear turtle with a PHD builds muscle. AB - Phosphoinositides are a family of phospholipid messenger molecules that control various aspects of cell biology in part by interacting with and regulating downstream protein partners. Importantly, phosphoinositides are present in the nucleus. They form part of the nuclear envelope and are present within the nucleus in nuclear speckles, intra nuclear chromatin domains, the nuclear matrix and in chromatin. What their exact role is within these compartments is not completely clear, but the identification of nuclear specific proteins that contain phosphoinositide interaction domains suggest that they are important regulators of DNA topology, chromatin conformation and RNA maturation and export. The plant homeo domain (PHD) finger is a phosphoinositide binding motif that is largely present in nuclear proteins that regulate chromatin conformation. In the present study I outline how changes in the levels of the nuclear phosphoinositide PtdIns5P impact on muscle cell differentiation through the PHD finger of TAF3 (TAF, TATA box binding protein (TBP)-associated factor), which is a core component of a number of different basal transcription complexes. PMID- 26862220 TI - Emerging evidence of signalling roles for PI(3,4)P2 in Class I and II PI3K regulated pathways. AB - There are eight members of the phosphoinositide family of phospholipids in eukaryotes; PI, PI3P, PI4P, PI5P, PI(4,5)P2, PI(3,4)P2, PI(3,5)P2 and PI(3,4,5)P3. Receptor activation of Class I PI3Ks stimulates the phosphorylation of PI(4,5)P2 to form PI(3,4,5)P3. PI(3,4,5)P3 is an important messenger molecule that is part of a complex signalling network controlling cell growth and division. PI(3,4,5)P3 can be dephosphorylated by both 3- and 5-phosphatases, producing PI(4,5)P2 and PI(3,4)P2, respectively. There is now strong evidence that PI(3,4)P2 generated by this route does not merely represent another pathway for removal of PI(3,4,5)P3, but can act as a signalling molecule in its own right, regulating macropinocytosis, fast endophilin-mediated endocytosis (FEME), membrane ruffling, lamellipodia and invadopodia. PI(3,4)P2 can also be synthesized directly from PI4P by Class II PI3Ks and this is important for the maturation of clathrin-coated pits [clathrin-mediated endocytosis (CME)] and signalling in early endosomes. Thus PI(3,4)P2 is emerging as an important signalling molecule involved in the coordination of several specific membrane and cytoskeletal responses. Further, its inappropriate accumulation contributes to pathology caused by mutations in genes encoding enzymes responsible for its degradation, e.g. Inpp4B. PMID- 26862222 TI - What's in a name? The clinical features of facioscapulohumeral muscular dystrophy. AB - Facioscapulohumeral muscular dystrophy (FSHD) is an inherited and progressive muscle disorder. Although its name suggests otherwise, it comprises weakness of the facial, shoulder and upper arm muscles, and also of the trunk and leg muscles. Its severity and disease course vary greatly and mild or early FSHD can be difficult to recognise. Knowledge of its subtle signs and symptoms can lead directly to the correct diagnosis without diagnostic delay and without needing multiple diagnostic procedures. We give an overview of the signs and symptoms of FSHD in severe as well as in mild cases, to facilitate correct and instant recognition of this relatively common muscle disorder. PMID- 26862221 TI - Electrochemical insights into the mechanism of NiFe membrane-bound hydrogenases. AB - Hydrogenases are enzymes of great biotechnological relevance because they catalyse the interconversion of H2, water (protons) and electricity using non precious metal catalytic active sites. Electrochemical studies into the reactivity of NiFe membrane-bound hydrogenases (MBH) have provided a particularly detailed insight into the reactivity and mechanism of this group of enzymes. Significantly, the control centre for enabling O2 tolerance has been revealed as the electron-transfer relay of FeS clusters, rather than the NiFe bimetallic active site. The present review paper will discuss how electrochemistry results have complemented those obtained from structural and spectroscopic studies, to present a complete picture of our current understanding of NiFe MBH. PMID- 26862223 TI - The Irish National Adverse Events Study (INAES): the frequency and nature of adverse events in Irish hospitals-a retrospective record review study. AB - INTRODUCTION: Irish healthcare has undergone extensive change recently with spending cuts and a focus on quality initiatives; however, little is known about adverse event occurrence. OBJECTIVE: To assess the frequency and nature of adverse events in Irish hospitals. METHODS: 1574 (53% women, mean age 54 years) randomly selected adult inpatient admissions from a sample of eight hospitals, stratified by region and size, across the Republic of Ireland in 2009 were reviewed using two-stage (nurse review of patient charts, followed by physician review of triggered charts) retrospective chart review with electronic data capture. Results were weighted to reflect the sampling strategy. The impact on adverse event rate of differing application of international adverse event criteria was also examined. RESULTS: 45% of charts were triggered. The prevalence of adverse events in admissions was 12.2% (95% CI 9.5% to 15.5%), with an incidence of 10.3 events per 100 admissions (95% CI 7.5 to 13.1). Over 70% of events were considered preventable. Two-thirds were rated as having a mild-to moderate impact on the patient, 9.9% causing permanent impairment and 6.7% contributing to death. A mean of 6.1 added bed days was attributed to events, representing an expenditure of ?5550 per event. The adverse event rate varied substantially (8.6%-17.0%) when applying different published adverse event eligibility criteria. CONCLUSIONS: This first study of adverse events in Ireland reports similar rates to other countries. In a time of austerity, adverse events in adult inpatients were estimated to cost over ?194 million. These results provide important baseline data on the adverse event burden and, alongside web based chart review, provide an incentive and methodology to monitor future patient-safety initiatives. PMID- 26862225 TI - Strengthening Screening for HIV, Hepatitis C, and STIs: An Innovative Partnership Between the Health Department and Community Health Centers in New York City. AB - In New York City, federally qualified health centers (FQHCs) are ideal partners for health departments because of their location in neighborhoods with high rates of HIV, hepatitis C virus (HCV) infection, and gonorrhea. Providers have experienced many barriers to following screening and treatment recommendations. In 2013, the New York City Department of Health and Mental Hygiene partnered with six FQHCs, representing 14 clinics, to make screening for HIV and HCV routine and increase adherence to gonorrhea treatment guidelines through education, electronic health record modification, and progress tracking. After one year, 12 of 14 clinics documented improvement in their HIV offer rate, and 11 clinics documented improvement in their HIV screening rate. Patients who were offered HIV screening increased from 26% at baseline to 56% at follow-up, and patients screened for HIV increased from 25% at baseline to 38% at follow-up. Most clinics improved their HIV screening rate, and progress suggests that local health departments can help FQHCs increase their HIV screening rates. PMID- 26862224 TI - Routine Screening for HIV Infection in Medical Care Settings: A Decade of Progress and Next Opportunities. PMID- 26862226 TI - Integrating Routine HIV Screening in the New York City Community Health Center Collaborative. AB - OBJECTIVE: One in seven of the 1.1 million people living in the United States infected with HIV are not aware of their HIV status. At the same time, many clinical settings have not adopted routine HIV screening, which promotes linkage to specialist medical care. We sought to improve HIV screening in a large community health center network by using a data-driven, collaborative learning approach and system-wide modifications, where counselor-based HIV screening and testing were replaced by health-care providers and medical assistants. METHODS: Urban Health Plan, Inc., a network of federally qualified health centers in the boroughs of the Bronx and Queens in New York City, provided HIV screening training for its health-care providers. In January 2011, it modified its electronic medical record system to incorporate HIV test offering. This study compared the 2010 baseline year with the three-year implementation follow-up period (January 2011 through December 2013) to determine the number of eligible individuals for HIV testing, HIV tests offered and performed, HIV-positive individuals, and HIV cases linked to specialty care. RESULTS: A total of 26,853 individuals at baseline and 100,369 individuals in the implementation period were eligible for HIV testing. HIV testing was performed on 2,079 (8%) of 26,853 eligible individuals in 2010 and 49,646 (50%) of 100,369 eligible individuals from 2011 through 2013. HIV-positive status was determined in 19 (0.9%) of 2,079 tested individuals in 2010 and 166 (0.3%) of 49,646 tested individuals from 2011 through 2013. Linkage to care was observed in all 19 eligible individuals and 127 (77%) of 166 eligible individuals who tested HIV positive in 2010 and 2011-2013, respectively. CONCLUSION: This study enabled routine HIV implementation testing at a community health center network, which resulted in enhanced HIV testing, an increased number of HIV-positive cases identified, and a rise in the number of patients linked to HIV specialist care. PMID- 26862227 TI - Experiences Implementing a Routine HIV Screening Program in Two Federally Qualified Health Centers in the Southern United States. AB - OBJECTIVE: The southern United States is highly affected by HIV, and community health centers play a key role in addressing the health-care needs of residents of southern cities. In 2012, Southside Medical Care Services ("Southside") in Atlanta, Georgia, and Central Care Community Health Center ("Central Care") in Houston, Texas, began comprehensive programs for routine HIV screening and linkage to HIV care. METHODS: We examined patient-level testing outcomes using medical record-derived data. We also compared the total number of HIV tests and HIV-positive tests in the most recent 12 months of the program with the number of HIV tests and HIV-positive tests during the 12 months prior to the program start. RESULTS: Southside saw 52,437 eligible patients from June 2012 through April 2014; 41,720 (80%) were offered an HIV test, 11,092 (27% of those offered a test) were tested, 75 (0.7% of those tested) had a positive result, and 74 (99% of those with a positive result) were linked to HIV care. Compared with the 12 months prior to the start of routine HIV screening implementation, Southside's routine HIV screening program conducted 5,955 more HIV tests (733% increase) and had 31 more patients who tested positive (238% increase). Central Care saw 22,658 eligible patients from July 2012 to April 2014; 10,904 (48%) were offered an HIV test, 9,909 (91% of those offered a test) were tested, 52 (0.5% of those tested) had a positive result, and 41 (79% of those with a positive result) were linked to HIV care. Compared with the 12 months before routine HIV screening was implemented, Central Care's routine HIV screening program conducted 4,559 more HIV tests (618% increase) and had 36 more patients who tested positive (600% increase). CONCLUSION: Southside and Central Care effectively implemented routine HIV screening programs that dramatically increased their testing volume while also linking the majority of HIV-positive patients to care. Other community health centers should consider similar programs. PMID- 26862228 TI - Routine HIV Screening in an Urban Community Health Center: Results from a Geographically Focused Implementation Science Program. AB - OBJECTIVE: CDC has recommended routine HIV screening since 2006. However, few community health centers (CHCs) routinely offer HIV screening. Research is needed to understand how to implement routine HIV screening programs, particularly in medically underserved neighborhoods with high rates of HIV infection. A routine HIV screening program was implemented and evaluated in a Philadelphia, Pennsylvania, neighborhood with high rates of HIV infection. METHODS: Implementation science is the study of methods to promote the integration of research findings and evidence into health-care policy and practice. Using an implementation science approach, the results of the program were evaluated by measuring acceptability, adoption, and penetration of routine HIV screening. RESULTS: A total of 5,878 individuals were screened during the program. HIV screening was highly accepted among clinic patients. In an initial needs assessment of 516 patients, 362 (70.2%) patients reported that they would accept testing if offered. Routine screening policies were adopted clinic-wide. Staff trainings, new electronic medical records that prompted staff members to offer screening and evaluate screening rates, and other continuing quality-improvement policies helped promote screenings. HIV screening offer rates improved from an estimated 5.0% of eligible patients at baseline in March 2012 to an estimated 59.3% of eligible patients in December 2014. However, only 5,878 of 13,827 (42.5%) patients who were offered screening accepted it, culminating in a 25.2% overall screening rate. Seventeen of the 5,878 patients tested positive, for a seropositivity rate of 0.3%. CONCLUSION: Routine HIV screening at CHCs in neighborhoods with high rates of HIV infection is feasible. Routine screening is an important tool to improve HIV care continuum outcomes and to address racial and geographic disparities in HIV infection. PMID- 26862230 TI - Ten Sites, 10 Years, 10 Lessons: Scale-up of Routine HIV Testing at Community Health Centers in the Bronx, New York. AB - OBJECTIVE: In response to the current CDC recommendations for routine HIV testing in clinical settings, the Adolescent AIDS Program at Montefiore Medical Center in the Bronx, New York, developed the Advise, Consent, Test, Support routine HIV testing model (ACTS) in 2003. ACTS was piloted in 10 community health centers operated by Montefiore because they serve populations most at risk for HIV/AIDS. METHODS: ACTS streamlined and codified the counseling and testing process, provided a routine HIV testing practice change plan, and provided training and communication materials that promoted routine HIV testing. To determine program success, we measured the number of patients seen at the clinics, the number of HIV test-eligible patients (those aged 13-64 years and not pregnant), the number and percent of patients receiving HIV testing, HIV test results, and the number of patients linked to care. RESULTS: HIV testing in the 10 sites increased nearly threefold during the pilot period (2003-2007), from 3,944 of 49,125 eligible patients (8%) tested in 2003 to 11,212 of 55,629 eligible patients (20%) tested in 2007. With little ongoing support, the sites continued or maintained improvements: 13,226 of 56,686 eligible patients (23%) were tested in 2008, 15,965 of 57,025 eligible patients (28%) were tested in 2011, 17,483 of 60,514 eligible patients (29%) were tested in 2012, and 17,971 of 63,172 eligible patients (28%) were tested in 2013. Sites identified 433 HIV-positive patients from 2006 to 2013 (0.2%-0.6% annual seropositivity), and 96% of them were linked to care within 90 days of HIV diagnoses (range: 92% to 98% annually). CONCLUSION: ACTS demonstrated that substantial and sustained increases in routine HIV testing can be achieved in health-care settings, not by adding personnel or financial resources, but by using the model's practice change plan and streamlined HIV testing approach. PMID- 26862231 TI - How Compliance Measures, Behavior Modification, and Continuous Quality Improvement Led to Routine HIV Screening in an Emergency Department in Brooklyn, New York. AB - OBJECTIVE: New York State adopted a new HIV testing law in 2010 requiring medical providers to offer an HIV test to all eligible patients aged 13-64 years during emergency room or ambulatory care visits. Since then, Wyckoff Heights Medical Center (WHMC) in Brooklyn, New York, began implementing routine HIV screening organization-wide using a compliance, behavior-modification, and continuous quality-improvement process. METHODS: WHMC first implemented HIV screening in the emergency department (ED) and evaluated progress with the following monthly indicators: HIV tests offered, HIV tests accepted, HIV tests ordered (starting in December 2013), HIV tests administered, positive HIV tests, and linkage to HIV care. Compliance with the delivery of HIV testing was determined by the proportion of patients who, after accepting a test, received one. RESULTS: During August 2013 through July 2014, of 57,852 eligible patients seen in the WHMC ED, a total of 31,423 (54.3%) were offered an HIV test. Of those, 8,229 (26.2%) patients accepted a test. Of those, 6,114 (74.3%) underwent a test. A total of 26 of the 6,114 patients tested (0.4%) had a positive test, and 24 of the 26 HIV positive patients were linked to HIV medical care. By July 2014, the monthly proportion of patients offered a test was 62%; the proportion of those offered a test who had a test ordered was 98%, and the proportion of those with a test ordered who were tested was 81%. Testing compliance increased substantially at the WHMC ED, from 77% in December 2013 to >98% in July 2014. CONCLUSION: Using compliance-monitoring, behavior-modification, and continuous quality-improvement processes produced substantial increases in offers and HIV test completion. WHMC is replicating this approach across departments, and other hospitals implementing routine HIV screening programs should consider this approach as well. PMID- 26862229 TI - Dual-Routine HCV/HIV Testing: Seroprevalence and Linkage to Care in Four Community Health Centers in Philadelphia, Pennsylvania. AB - OBJECTIVE: Despite common risk factors, screening for hepatitis C virus (HCV) and HIV at the same time as part of routine medical care (dual-routine HCV/HIV testing) is not commonly implemented in the United States. This study examined improvements in feasibility of implementation, screening increase, and linkage to care when a dual-routine HCV/HIV testing model was integrated into routine primary care. METHODS: National Nursing Centers Consortium implemented a dual routine HCV/HIV testing model at four community health centers in Philadelphia, Pennsylvania, on September 1, 2013. Routine HCV and opt-out HIV testing replaced the routine HCV and opt-in HIV testing model through medical assistant-led, laboratory-based testing and electronic medical record modification to prompt, track, report, and facilitate reimbursement for tests performed on uninsured individuals. This study examined testing, seropositivity, and linkage-to-care comparison data for the nine months before (December 1, 2012-August 31, 2013) and after (September 1, 2013-May 31, 2014) implementation of the dual-routine HCV/HIV testing model. RESULTS: A total of 1,526 HCV and 1,731 HIV tests were performed before, and 1,888 HCV and 3,890 HIV tests were performed after dual-routine testing implementation, resulting in a 23.7% increase in HCV tests and a 124.7% increase in HIV tests. A total of 70 currently HCV-infected and four new HIV seropositive patients vs. 101 HCV-infected and 13 new HIV-seropositive patients were identified during these two periods, representing increases of 44.3% for HCV antibody-positive and RNA-positive tests and 225.0% for HIV-positive tests. Linkage to care increased from 27 currently infected HCV--positive and one HIV positive patient pre-dual-routine testing to 39 HCV--positive and nine HIV positive patients post-dual-routine testing. CONCLUSION: The dual-routine HCV/HIV testing model shows that integrating dual-routine testing in a primary care setting is possible and leads to increased HCV and HIV screening, enhanced seropositivity diagnosis, and improved linkage to care. PMID- 26862232 TI - Costs of Expanded Rapid HIV Testing in Four Emergency Departments. AB - OBJECTIVE: The HIV Prevention Trials Network (HPTN) 065 trial sought to expand HIV screening of emergency department (ED) patients in Bronx, New York, and Washington, D.C. This study assessed the testing costs associated with different expansion processes and compared them with costs of a hypothetical optimized process. METHODS: Micro-costing studies were conducted in two participating EDs in each city that switched from point-of-care (POC) to rapid-result laboratory testing. In three EDs, laboratory HIV testing was only conducted for patients having blood drawn for clinical reasons; in the other ED, all HIV testing was conducted with laboratory testing. Costs were estimated through direct observation and interviews to document process flows, time estimates, and labor and materials costs. A hypothetical optimized process flow used minimum time estimates for each process step. National wage and fringe rates and local reagent costs were used to determine the average cost (excluding overhead) per completed nonreactive and reactive test in 2013 U.S. dollars. RESULTS: Laboratory HIV testing costs in the EDs ranged from $17.00 to $23.83 per completed nonreactive test, and POC testing costs ranged from $17.64 to $37.60; cost per completed reactive test ranged from $89.29 to $123.17. Costs of hypothetical optimized HIV testing with automated process steps were approximately 45% lower for nonreactive tests and 20% lower for reactive tests. The cost per ED visit to conduct expanded HIV testing in each hospital ranged from $1.21 to $3.96. CONCLUSION: An optimized process could achieve additional cost savings but would require an investment in electronic system interfaces to further automate testing processes. PMID- 26862233 TI - Scaling Up HIV Testing in an Academic Emergency Department: An Integrated Testing Model with Rapid Fourth-Generation and Point-of-Care Testing. AB - OBJECTIVE: We evaluated two approaches for implementing routine HIV screening in an inner-city, academic emergency department (ED). These approaches differed by staffing model and type of HIV testing technology used. The programmatic outcomes assessed included the total number of tests performed, proportion of newly identified HIV-positive patients, and proportion of newly diagnosed individuals who were linked to care. METHODS: This study examined specific outcomes for two distinct, successive approaches to implementing HIV screening in an inner-city, academic ED, from July 2012 through June 2013 (Program One), and from August 2013 through July 2014 (Program Two). Program One used a supplementary staff-only HIV testing model with point-of-care (POC) oral testing. Program Two used a triage integrated, nurse-driven HIV testing model with fourth-generation blood and POC testing, and an expedited linkage-to-care process. RESULTS: During Program One, 6,832 eligible patients were tested for HIV with a rapid POC oral HIV test. Sixteen patients (0.2%) were newly diagnosed with HIV, of whom 13 were successfully linked to care. During Program Two, 8,233 eligible patients were tested for HIV, of whom 3,124 (38.0%) received a blood test and 5,109 (62.0%) received a rapid POC test. Of all patients tested in Program Two, 29 (0.4%) were newly diagnosed with HIV, four of whom had acute infections and 27 of whom were successfully linked to care. We found a statistically significant difference in the proportion of the eligible population tested-8,233 of 49,697 (16.6%) in Program Two and 6,832 of 46,818 (14.6%) in Program One. These differences from Program One to Program Two corresponded to increases in testing volume (n=1,401 tests), number of patients newly diagnosed with HIV (n=13), and proportion of patients successfully linked to care (from 81.0% to 93.0%). CONCLUSION: Integrating HIV screening into the standard triage workflow resulted in a higher proportion of ED patients being tested for HIV as compared with the supplementary staff-only HIV testing model. New rapid fourth-generation testing technology allowed the identification of acute HIV infection and same-visit confirmation of a positive diagnosis. PMID- 26862234 TI - A Comparison of Parallel and Integrated Models for Implementation of Routine HIV Screening in a Large, Urban Emergency Department. AB - OBJECTIVE: This study compared two approaches for implementation of non-targeted HIV screening in the emergency department (ED): (1) designated HIV counselors screening in parallel with ED care and (2) nurse-based screening integrated into patient triage. METHODS: A retrospective analysis was performed to compare parallel and integrated screening models using data from the first 12 months of each program. Data for the parallel screening model were extracted from information collected by HIV test counselors and the electronic medical record (EMR). Integrated screening model data were extracted from the EMR and supplemented by data collected by HIV social workers during patient interaction. For both programs, data included demographics, HIV test offer, test acceptance or declination, and test result. A Z-test between two proportions was performed to compare screening frequencies and results. RESULTS: During the first 12 months of parallel screening, approximately 120,000 visits were made to the ED, with 3,816 (3%) HIV tests administered and 65 (2%) new diagnoses of HIV infection. During the first 12 months of integrated screening, 111,738 patients were triaged in the ED, with 16,329 (15%) patients tested and 190 (1%) new diagnoses. Integrated screening resulted in an increased frequency of HIV screening compared with parallel screening (0.15 tests per ED patient visit vs. 0.03 tests per ED patient visit, p<0.001) and an increase in the absolute number of new diagnoses (190 vs. 65), representing a slight decrease in the proportion of new diagnoses (1% vs. 2%, p=0.007). CONCLUSION: Non-targeted, integrated HIV screening, with test offer and order by ED nurses during patient triage, is feasible and resulted in an increased frequency of HIV screening and a threefold increase in the absolute number of newly identified HIV-positive patients. PMID- 26862235 TI - Evolution and Escalation of an Emergency Department Routine, Opt-out HIV Screening and Linkage-to-Care Program. AB - OBJECTIVE: The Centers for Disease Control and Prevention has recommended emergency department (ED) opt-out HIV screening since 2006. Routine screening can prove challenging due to the ED's complexity and competing priorities. This study examined the implementation and evolution of a routine, integrated, opt-out HIV screening program at an urban academic ED in Alabama since August 2011. METHODS: ED routine, opt-out HIV screening was implemented as a standard of care in September 2011. To describe the outcomes and escalation of the screening program, data analyses were performed from three separate data queries: (1) encounter level HIV screening questionnaire and test results from September 21, 2011, through December 31, 2013; (2) test-level, fourth-generation HIV results from July 9 through December 31, 2013; and (3) daily HIV testing rates and trends from September 9, 2011, through June 30, 2014. RESULTS: Of the 46,385 HIV screening tests performed, 252 (0.5%) were confirmed to be positive. Acute HIV infection accounted for 11.8% of all HIV patients identified using the fourth-generation HIV screening assay. Seventy-six percent of confirmed HIV-positive patients had successful linkage to care. Implementation of fourth-generation HIV instrument based testing resulted in a 15.0% decline in weekly HIV testing rates. Displacement of nursing provider HIV test offers from triage to the bedside resulted in a 31.6% decline in weekly HIV testing rates. CONCLUSION: This program demonstrated the capacity for high-volume, routine, opt-out HIV screening. Evolving ED challenges require program monitoring and adaptation to sustain scalable HIV screening in EDs. PMID- 26862237 TI - Implementing Routine HIV Screening in Three Chicago Hospitals: Lessons Learned. AB - OBJECTIVE: This study describes routine HIV screening implementation and outcomes in three hospitals in Chicago, Illinois. METHODS: Retrospective data from three hospitals were examined, and routine testing procedures, testing volume, reactive test results, and linkage-to-care outcomes were documented. RESULTS: From January 2012 through March 2014, 40,788 HIV tests were administered at the three hospitals: 18,603 (46%) in the emergency department (ED), 7,546 (19%) in the inpatient departments, and 14,639 (36%) in outpatient clinics. The screened patients varied from 1% to 22% of the total eligible patient population across hospitals. A total of 297 patients tested positive for HIV for a seropositivity rate of 0.7%; 129 (43%) were newly diagnosed and 168 (57%) were previously diagnosed, with 64% of those previously diagnosed out of care at the time of screening. The inpatient areas had the highest seropositivity rate (0.6%). The percentage of newly diagnosed patients overall who were linked to care was 77%. Of newly diagnosed patients, 51% had >= 1 missed opportunity for testing (with a mean of 3.8 visits since 2006), and 30% of patients with missed opportunities were late testers (baseline CD4+ counts <200 cells per cubic millimeter). CONCLUSION: Routine screening is an essential tool for identifying new infections and patients with known infection who are out of care. Hospitals need to provide HIV screening in inpatient and outpatient settings--not just EDs--to decrease missed opportunities. Routine screening success will be driven by how notification and testing are incorporated into the normal medical flow, the level of leadership buy-in, the ability to conduct quality assurance, and local testing laws. PMID- 26862236 TI - Expanded HIV Testing and Linkage to Care: Conventional vs. Point-of-Care Testing and Assignment of Patient Notification and Linkage to Care to an HIV Care Program. AB - OBJECTIVE: The University of Chicago Medicine (UCM) led the Expanded Testing and Linkage to Care (X-TLC) program for disproportionately affected populations on the South Side of Chicago. The X-TLC program aimed to expand routine HIV testing to high-prevalence communities with disproportionately affected populations (i.e., minority men and women, men who have sex with men, and intravenous drug users) according to CDC guidelines at multiple clinical sites. METHODS: The X-TLC program used standard blood-based laboratory testing vs. point-of-care rapid testing or rapid laboratory testing with point-of-care results notification. Site coordinators and the linkage-to-care coordinator at UCM oversaw testing, test notification, and linkage to care. RESULTS: From February 1, 2011, through December 31, 2013, the X-TLC program completed 75,345 HIV tests on 67,153 unique patients. Of the total tests, 48,044 (63.8%) were performed on patients who self identified as African American and 6,606 (8.8%) were performed on patients who self-identified as Hispanic. Of the 67,153 patients tested, 395 (0.6%) tested positive and 176 (0.3%) were previously unaware of their HIV-positive status. Seroprevalence was even higher for EDs, where 127 of 12,957 patients tested positive for HIV (1.0% seroprevalence), than for other patient care sites, including for new diagnoses, where 50 of 12,957 patients tested positive for HIV (0.4% seroprevalence). Of the 176 newly diagnosed patients, 166 of 173 (96.0%) patients who were still alive when testing was complete received their test results, and 148 of the 166 patients who were eligible for care (89.0%) were linked to care. Patients linked to X-TLC physicians did well with respect to the continuum of care: 77 of 123 (62.6%) patients achieved HIV viral load of <200 copies/milliliter. CONCLUSION: Lead organizations such as UCM were able to assist and oversee HIV screening and linkage to care for HIV patients diagnosed at community sites. HIV screening and linkage to care can be accomplished by incorporating standard testing for HIV into routine medical care. PMID- 26862238 TI - Integrating Routine HIV Testing into Family Planning Clinics That Treat Adolescents and Young Adults. AB - OBJECTIVE: Adolescents and young adults remain at high risk for new HIV infections and for unknowingly transmitting the virus to others. Yet, they have demonstrated low rates of testing due to barriers such as stigma and difficulty accessing testing services. Few existing programs have successfully integrated family planning and HIV care services to improve testing and diagnosis rates among young adults and adolescents, particularly those of minority groups. This study describes the process of implementing HIV services into family planning clinics and how to train staff in routine, opt-out testing. METHODS: This study used HIV screening data from 10 family planning clinics serving adolescents and young adults in Houston, Texas. A total of 34,299 patients were tested for HIV during a 48-month study period, from January 2010 through December 2014. RESULTS: Patients tested included minors <18 years of age (25.5%), males (22.8%), and individuals who had missed opportunities for HIV testing at other health-care settings. From the opt-in period (2006-2007) to the routine, opt-out period (2008 2010), the yearly average number of tests administered more than doubled; the yearly average increased again by 50% from the routine, opt-out period to the routine, rapid period (2011-2014). Eighty-eight (0.3%) patients were diagnosed with HIV, a higher seropositivity rate than CDC's recommended threshold of 0.1% for settings where routine screening is warranted. CONCLUSION: Routine, opt-out HIV testing integrated into family planning clinics increased rates of testing acceptance, receipt of test results, and HIV-positive diagnoses among adolescents and young adults. PMID- 26862240 TI - Designing Decision Support System to Detect Drug Interactions Type 2 Diabetes. AB - BACKGROUND AND AIM: Type II Diabetes is the most common diseases of metabolic disorders and the treatment of oral anti-diabetic drug use takes place But The problem of using multi-drug and interactions at the same time is an issue that has always been a major challenge And diagnosis of drug interactions, particularly in Diabetic patients due to the problem with the disease is very important. The purpose of this studying is, to design a clinical assistant decided to use this approach to determine the type II diabetes drug interactions this makes it easy for those who are active in the field. MATERIALS AND METHODS: Study is Developmental that to determine the content of the system a self-made checklist was used. Checklist Validity and reliability has been confirmed by four professors. The Research community to determine the content of the system was country endocrine that are 124 people. The sample size was calculated using Cochran that was 57 people. The Score of checklist was calculated in SPSS version 20 .finally, the checklist was approved by at least 70% points. The system by using Microsoft SQL server 2008 and visual Studio 2012 development environment was designed in C#.net. In the end, In order to evaluate the software to determine the level of satisfaction, usability and ease of use, designed systems sharing with all Medical Informatics students of Tehran University of Medical Sciences. For this purpose a self-made questionnaire was used. Questionnaire Validity has been confirmed by four professors and reliability was assessed by Cronbach method. RESULTS: The results of the survey are showing that the majority of students found out and believed the software is useful and easy to use and generally expressed their satisfaction software. CONCLUSIONS: The methodology provides a suitable approach for analysis and modeling of data in the medical field and the performance is good. PMID- 26862239 TI - Pharmacy Intervention to Improve HIV Testing Uptake Using a Comprehensive Health Screening Approach. AB - OBJECTIVE: HIV testing is increasingly available, yet barriers to HIV testing persist for low-income black and Latino people, especially those who use illicit drugs. HIV exceptionalism, or the idea that a positive HIV diagnosis is drastically different from a diagnosis for any other disease, may influence HIV testing-related stigma, resulting in reduced willingness to undergo HIV testing. This pharmacy-based intervention combined HIV testing with less stigmatized chronic disease screening tests (e.g., blood pressure, glucose, and cholesterol) to equate the concept of an HIV diagnosis with other diagnoses. METHODS: Three pharmacies located in low-income, minority neighborhoods in New York City were enrolled in an intervention to provide (1) HIV testing, chronic disease screening, and a healthy lifestyles video that normalized all screening tests and destigmatized HIV as a fatal disease (comprehensive arm); (2) HIV testing and the video (video arm); and (3) HIV testing only (control arm). Injection drug users (IDUs) and pharmacy staff recruited un- and underinsured pharmacy customers, IDUs, and IDU peers from 2010 to 2012. Participants in the control group were compared with those in the comprehensive and video intervention groups. RESULTS: Participants in the comprehensive arm (prevalence ratio [PR] = 1.61, 95% confidence interval [CI] 1.03, 2.49, p=0.08) and the video arm (PR=1.59, 95% CI 1.00, 2.53, p=0.09) were marginally significantly more likely to receive an HIV test in the pharmacy compared with those in the control arm after adjustment. CONCLUSIONS: These findings suggest that adoption of strategies that destigmatize and normalize HIV testing can improve uptake. Implementation of this strategy in low-access, minority communities with high HIV prevalence and among high-risk populations may help reduce racial/ethnic disparities in HIV. PMID- 26862241 TI - The Event-related Potential P300 in Patients with Migraine. AB - OBJECTIVE: Recording of event-related potentials by using oddball paradigm of auditory P300 has yielded conflicting results in migraine. The aim of this study was to demonstrate that migraine patients have reduced P300 amplitude and prolonged P300 latency, suggesting alterations of the cognitive-evaluative component. METHODS: We recruited 29 migraine patients (24 females; median age 40 years) and 29 healthy age- and gender-matched participants. Participants were subjected to the same testing procedures of auditory P300 by discrimination the target auditory stimulus from the frequent stimulus, and analyzing P300 target/frequent stimulus amplitudes, and P300 target/frequent stimulus latencies. RESULTS: Patients with migraine don't have prolonged P300 target stimulus latency, but have a longer P300 frequent stimulus latency for 17.5ms. Out of 29 participants with migraine 8 had pathological P300 target stimulus amplitude, and 19 had pathological P300 frequent stimulus amplitude. CONCLUSION: People with migraine have altered the P300 which indicates the presence of cognitive dysfunction in these patients and importance of early diagnosis and intervention to preventing any deterioration in cognitive functions. PMID- 26862242 TI - Interictal Electroencephalography (EEG) Findings in Children with Epilepsy and Bilateral Brain Lesions on Magnetic Resonance Imaging (MRI). AB - INTRODUCTION: Neuroimaging procedures and electroencephalography (EEG) are basic parts of investigation of patients with epilepsies. AIM: The aim is to try to assess relationship between bilaterally localized brain lesions found in routine management of children with newly diagnosed epilepsy and their interictal EEG findings. PATIENTS AND METHODS: Total amount of 68 patients filled criteria for inclusion in the study that was performed at Neuropediatrics Department, Pediatric Hospital, University Clinical Center Sarajevo, or its outpatient clinic. There were 33 girls (48,5%) and 35 boys (51,5%). Average age at diagnosis of epilepsy was 3,5 years. RESULTS: Both neurological and neuropsychological examination in the moment of making diagnosis of epilepsy was normal in 27 (39,7%) patients, and showed some kind of delay or other neurological finding in 41 (60,3%). Brain MRI showed lesions that can be related to antenatal or perinatal events in most of the patients (ventricular dilation in 30,9%, delayed myelination and post-hypoxic changes in 27,9%). More than half of patients (55,9%) showed bilateral interictal epileptiform discharges on their EEGs, and further 14,7% had other kinds of bilateral abnormalities. Frequency of bilateral epileptic discharges showed statistically significant predominance on level of p<0,05. Cross tabulation between specific types of bilateral brain MRI lesions and EEG finding did not reveal significant type of EEG for assessed brain lesions. CONCLUSION: We conclude that there exists relationship between bilaterally localized brain MRI lesions and interictal bilateral epileptiform or nonspecific EEG findings in children with newly diagnosed epilepsies. These data are suggesting that in cases when they do not correlate there is a need for further investigation of seizure etiology. PMID- 26862243 TI - Comparison of Glucocorticoid (Budesonide) and Antileukotriene (Montelukast) Effect in Patients with Bronchial Asthma Determined with Body Plethysmography. AB - OBJECTIVE: Effect of glucocorticoids-budesonide and antileukotriene-montelukast in patients with bronchial asthma and bronchial increased reactivity was studied in this work. METHODS: Parameters of the lung function are determined with Body plethysmography. Raw and ITGV were registered and specific resistance (SRaw) was also calculated. RESULTS: Results of this research, in patients with bronchial asthma, indicate that glucocorticoids - budesonide (Pulmicort; 2 * 2 mg inh) has significant action (p< 0.01) on reduction of the specific resistance (SRaw) of airways, applied to the same patients 3 days after administration of montelukast, at home (2 * 10 mg). Three days after administration of the montelukast, antileukotriene medicine, at home, on the fourth day same patients administered a capsule of montelukast, 10 mg dose per os, and significantly (p < 0.05) reduced the increased bronchomotor tonus; and the effect of the control with salbutamol (beta2-adrenergic agonist) is effective in removal of the increased bronchomotor tonus, causing significant decrease of the resistance (Raw), respectively of the specific resistance (SRaw), (p < 0, 01). CONCLUSION: This suggests that the bronchodilator effect of glucocorticoids is more powerful than of the leukotriene, because glucocorticoids terminate the early stage of chemical mediator release (prostaglandins PgD2, SRS, and leukotriene LTC4, LTD4, LTE4 and Cytokinins also etc.) as powerful bronchoconstriction substances, whilst antileukotriene substances does not have this feature. PMID- 26862244 TI - Pachymetric Changes of the Cornea Amongst Patients Treated with LASIK. AB - PURPOSE: In this study, we have researched the possible parametrically changes before and after LASIK (laser-assisted in situ keratomileusis) and the influence of these changes in the cause of post LASIK ectasia. MATERIALS AND METHODS: In this study 204 eyes with different refractive anomalies were included. Candidates that underwent refractive surgery first have to undergo many ophthalmological examinations, firstly by evaluating their visual acuity, subjective and objective refraction with and without cycloplegia, slight lamp evaluation, computerized topography, pupillometry, retina examination and measurement of intraocular pressure. Pachymetric values were measured with Orbscan IIz (Bausch - Lomb). Refractive surgery was done with LASIK under local anesthesia. RESULTS: In this study 102 patients were treated with LASIK who were with different refractive anomalies. According to the group age 44 or 43.1% were of the age 20 - 29, 46 or 45.1% were of the age 30 - 39, 11 or 10.8% were 40 - 49 years of age and 1 or 1% were above the age of 50 +. Pachymetric before surgery in right eye was approximately 565.4 um (DS+- 39.4), from 507 um up to 678 um, but after surgery it was approximately 497.5 um (DS+-61.7) from 346 um up to 644 um. Pachymetric on the left eye before surgery was approximately 564.8 um (DS+-41.5) from 504 um up to 696 um but after surgery it was approximately 498.3 um (DS+-62.2), from 329 um up to 646 um. Pachymetric in both eyes before surgery was approximately 549.1 um (DS+=73.9), from 263 um up to 687 um. Pachymetric on both eyes after surgery was approximately 496.9 um (DS+-60.1), from 337.5 um up to 645 um. With the " Paired T - test " we have reached a significant statistical change between the pachymetric values in both eyes before and after the surgery (P<0.0001). CONCLUSION: Corneal thickness is one of the main criteria in order to allow refractive surgeries, and as the main criteria it was evaluated at our patients treated with LASIK. PMID- 26862245 TI - The Usage of Association Rule Mining to Identify Influencing Factors on Deafness After Birth. AB - BACKGROUND: Providing complete and high quality health care services has very important role to enable people to understand the factors related to personal and social health and to make decision regarding choice of suitable healthy behaviors in order to achieve healthy life. For this reason, demographic and clinical data of person are collecting, this huge volume of data can be known as a valuable resource for analyzing, exploring and discovering valuable information and communication. This study using forum rules techniques in the data mining has tried to identify the affecting factors on hearing loss after birth in Iran. MATERIALS AND METHODS: The survey is kind of data oriented study. The population of the study is contained questionnaires in several provinces of the country. First, all data of questionnaire was implemented in the form of information table in Software SQL Server and followed by Data Entry using written software of C # .Net, then algorithm Association in SQL Server Data Tools software and Clementine software was implemented to determine the rules and hidden patterns in the gathered data. FINDINGS: Two factors of number of deaf brothers and the degree of consanguinity of the parents have a significant impact on severity of deafness of individuals. Also, when the severity of hearing loss is greater than or equal to moderately severe hearing loss, people use hearing aids and Men are also less interested in the use of hearing aids. CONCLUSION: In fact, it can be said that in families with consanguineous marriage of parents that are from first degree (girl/boy cousins) and 2(nd) degree relatives (girl/boy cousins) and especially from first degree, the number of people with severe hearing loss or deafness are more and in the use of hearing aids, gender of the patient is more important than the severity of the hearing loss. PMID- 26862246 TI - Gender Differences in Biochemical and Electroneurographic Parameters of Median and Ulnar Nerve. AB - INTRODUCTION: In this article are demonstrated differences in the aspects of the metabolic syndrome (MSy) between genders, as well as the association of MSy and neuropathy. THE AIM: The aim of our study was that in patients with newly discovered metabolic syndrome of both sexes make comparison of fasting blood glucose levels and after oral glucose tolerance test, as well as neurophysiological parameters of n.medianus and n.ulnaris. PATIENTS AND METHODS: All participants were examined dermatologically. The analysis included the 36 male and 36 female respondents with a newly discovered MSy. RESULTS: The average age of men was 52.75+/-7.5 (40-65) years and women 52.1+/-7.7 (38-67) years. The average value of fasting blood glucose in women was 5.86+/-0.87 (4.5-8) mmol/L, and non significantly higher in men (p=0.0969) as 6.19+/-0.8 (4.7-8) mmol/L. Average values of blood sugar 120 minutes after oral glucose tolerance test were not significantly different (p=0.7052), and was 5.41+/-1.63 (3.3-9.7) mmol/L in women and 5.27+/-1.52 (2.7-9.8) mmol/L in men. Median motor velocity were significantly higher in women for n.medianus on the left (p=0.0024), n.ulnaris on the left (p=0.0081) and n.ulnaris on the right side (p=0.0293), and the median motor terminal latency were significantly longer in n.ulnaris on the left (p=0.0349) and n.ulnaris on the right side (p=0.011). There was no significant difference in the sensory conductivity velocity in n.medianus and n.ulnaris between the groups, but the amplitude with the highest peak of the sensory response was significantly higher in n.medianus on the left (p=0.0269) and n.ulnaris on the left side (p=0.0009) in female patients. CONCLUSION: The results indicate that there are differences in neurophysiological parameters of the investigated nerves between the genders, and that tested nerve structures in the course of MSy are affected slightly more in men. There were no significant differences in skin changes between genders. PMID- 26862247 TI - Computer Based Assessment of Cervical Vertebral Maturation Stages Using Digital Lateral Cephalograms. AB - OBJECTIVE: This study was aimed to investigate the reliability of a computer application for assessment of the stages of cervical vertebra maturation in order to determine the stage of skeletal maturity. MATERIAL AND METHODS: For this study, digital lateral cephalograms of 99 subjects (52 females and 47 males) were examined. The following selection criteria were used during the sample composition: age between 9 and 16 years, absence of anomalies of the vertebrae, good general health, no history of trauma at the cervical region. Subjects with lateral cephalograms of low quality were excluded from the study. For the purpose of this study a computer application Cephalometar HF V1 was developed. This application was used to mark the contours of the second, third and fourth cervical vertebrae on the digital lateral cephalograms, which enabled a computer to determine the stage of cervical vertebral maturation. The assessment of the stages of cervical vertebral maturation was carried out by an experienced orthodontist. The assessment was conducted according to the principles of the method proposed by authors Hassel and Farman. The degree of the agreement between the computer application and the researcher was analyzed using by statistical Cohen Kappa test. RESULTS: The results of this study showed the agreement between the computer assessment and the researcher assessment of the cervical vertebral maturation stages, where the value of the Cohen Kappa coefficient was 0.985. CONCLUSION: The computer application Cephalometar HF V1 proved to be a reliable method for assessing the stages of cervical vertebral maturation. This program could help the orthodontists to identify the stage of cervical vertebral maturation when planning the orthodontic treatment for the patients with skeletal disharmonies. PMID- 26862248 TI - The Evaluation of SEPAS National Project Based on Electronic Health Record System (EHRS) Coordinates in Iran. AB - BACKGROUND: Electronic Health Records (EHRs) are secure private lifetime records that can be shared by using interoperability standards between different organizations and units. These records are created by the productive system that is called EHR system. Implementing EHR systems has a number of advantages such as facilitating access to medical records, supporting patient care, and improving the quality of care and health care decisions. The project of electronic health record system in Iran, which is the goal of this study, is called SEPAS. With respect to the importance of EHR and EHR systems the researchers investigated the project from two perspectives: determining the coordinates of the project and how it evolved, and incorporating the coordinates of EHR system in this project. METHODS: In this study two evaluation tools, a checklist and a questionnaire, were developed based on texts and reliable documentation. The questionnaire and the checklist were validated using content validity by receiving the experts' comments and the questionnaire's reliability was estimated through Test-retest(r =87%). Data were collected through study, observation, and interviews with experts and specialists of SEPAS project. RESULTS: This research showed that SEPAS project, like any other project, could be evaluated. It has some aims; steps, operational phases and certain start and end time, but all the resources and required facilities for the project have not been considered. Therefore it could not satisfy its specified objective and the useful and unique changes which are the other characteristics of any project have not been achieved. In addition, the findings of EHR system coordinates can be determined in 4 categories as Standards and rules, Telecommunication-Communication facilities, Computer equipment and facilities and Stakeholders. CONCLUSIONS: The findings indicated that SEPAS has the ability to use all standards of medical terminology and health classification systems in the case of Maksa approval (The reference health coding of Iran). ISO13606 was used as the main standard in this project. Regarding the telecommunication-communication facilities of the project, the findings showed that its link is restricted to health care centers which does not cover other institutions and organizations involved in public health. The final result showed that SEPAS is in the early stages of execution. And the full implementation of EHR needs the provision of the infrastructure of the National Health Information Network that is the same as EHR system. PMID- 26862249 TI - Epilepsy Research in Iran: a Scientometric Analysis of Publications Output During 2000-2014. AB - AIM: The aim of this study is to analyze the epilepsy research output of Iran in national and global contexts, as reflected in its publication output indexed in Scopus citation database during 2000-2014. METHODS: This study was based on the publications of epilepsy research from Iranian authors retrieved Feb. 2015 from Scopus Citation database [www.scopus.com]. The string used to retrieve the data was developed using "epilepsy OR epilepsies" keywords in title, abstract and keywords and Iran in affiliation field was our main string. RESULTS: Cumulative publication output of Iran in epilepsy research consisted of 702 papers from 2000 to 2014, with an average number of 46.53 papers per year. The total publication output of Iran in epilepsy research increased from 2 papers in 2000 to 88 papers in 2014. Hence, with 702 paper, Iran ranked 25(th) among the top 25 countries with a global share of 0.82 %. Iranian publication average citation per paper increased from 0 in 2000 to 7.88 in 2014. Overall, the received citations were 3184 citations during those years. CONCLUSION: Iran is collaborating with 36 countries with no more than 244 of its papers (35% of its total papers). It is necessary to prepare conditions for epilepsy researchers to collaborate more with international scientific societies in order to produce more and high quality papers. PMID- 26862250 TI - Research on the Submission, Acceptance and Publication Times of Articles Submitted to International Otorhinolaryngology Journals. AB - OBJECTIVE: The aim of this study was to provide insight into the acceptance and publication times of articles submitted to international otolaryngology journals. MATERIAL AND METHODS: The study was carried out by examining the top 37 journal titles returned in an online search for otolaryngology journals published from 1999 to 2013 that have an international status based on their impact factor. RESULTS: In total, 9,765 publications were examined. When journals were compared based on journal impact factor, statistically significant differences (p<0.01) were found. Comparisons of the acceptance and publication times for both original research and case reports revealed that these times have become shorter over the years. DISCUSSION: Journals with higher impact factors likely have larger workloads in terms of articles, and consequently, their acceptance and publication times might be longer. An implication from this study finding that these periods have decreased over the years is that these processes can be expedited by more intensive use of the Internet and increases in journal capacity and number of issues published. CONCLUSION: The expedition of these processes over time might result from journals' ability to use technology more intensively or from increases in journal's capacity and number of issues published. PMID- 26862251 TI - Discovering Diabetes Complications: an Ontology Based Model. AB - BACKGROUND: Diabetes is a serious disease that spread in the world dramatically. The diabetes patient has an average of risk to experience complications. Take advantage of recorded information to build ontology as information technology solution will help to predict patients who have average of risk level with certain complication. It is helpful to search and present patient's history regarding different risk factors. Discovering diabetes complications could be useful to prevent or delay the complications. METHOD: We designed ontology based model, using adult diabetes patients' data, to discover the rules of diabetes with its complications in disease to disease relationship. RESULT: Various rules between different risk factors of diabetes Patients and certain complications generated. Furthermore, new complications (diseases) might be discovered as new finding of this study, discovering diabetes complications could be useful to prevent or delay the complications. CONCLUSION: The system can identify the patients who are suffering from certain risk factors such as high body mass index (obesity) and starting controlling and maintaining plan. PMID- 26862252 TI - The Comparison of the Minimum Data Set for Elderly Health in Selected Countries. AB - INTRODUCTION: Ongoing increase in the elderly population in many developed countries has drawn attention to health of this age group. Recording adequate and relevant data for the elderly is considered as the basis for future planning for this segment of society. So this study was conducted to compare minimum data about elderly health in selected countries. METHODS: This review study was conducted through Internet and library studies. Key words were extracted from search engines and data bases including Google, Yahoo, Google Scholar, PubMed, ProQuest and Iranian National Medical Digital Library. Inclusion criteria included English language with no time limits. All articles, research projects, theses, guidelines and progress reports were retrieved from the United States, Sweden, Japan and Iran and reviewed. Also, websites of organizations responsible for elderly health in selected countries were visited and their documents were reviewed. Results from this search were provided narratively and finally were presented within comparison tables. FINDINGS: The findings of this study showed that elderly data in the selected countries are collected around four axis including minimum demographic data, medical histories, health assessment and financial data of elderly health. DISCUSSION AND CONCLUSION: Given the importance of the minimum data set of elderly health for future planning, the use of experiences of leading countries in elderly health seems necessary; however, localization of it according to the country's needs is inevitable. PMID- 26862253 TI - The Most Influential Scientist in the Development of Medical informatics (9): William Abbott. PMID- 26862254 TI - Amelioration Effect of Zinc and Iron Supplementation on Selected Oxidative Stress Enzymes in Liver and Kidney of Cadmium-Treated Male Albino Rat. AB - Cadmium (Cd) is a highly toxic, nonessential heavy metal with many industrial uses that can contribute to a well-defined spectrum of diseases in animals as well as in humans. The present study examines the effect of zinc (Zn) and iron (Fe) supplementation on oxidative stress enzymes in Cd-treated rats. Wistar strain male albino rats were treated with cadmium chloride (CdCl2) at a dose of 1/10(th) LD50/48 h, that is, 22.5 mg/kg body weight for 7, 15, and 30 days (d) time intervals. The 15d Cd-treated rats were divided into three groups. The first group received Zn (12 mg/kg), second group Fe (40 mg/kg) alone, and third group supplemented with both Zn and Fe and observed for 7, 15, and 30d. After the specific time intervals, rats were decapitated and oxidative stress enzymes like catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) were assayed in liver and kidney. Simultaneously lipid peroxidation (LPO) levels were also measured. A significant elevation in LPO levels with decreased activity levels of CAT, SOD, GPx, and GST were observed during Cd intoxication. With Zn and/or Fe supplementation, a significant reversal in the oxidative stress enzymes was observed. Our study reveals that combination of Zn and Fe supplementation is effective in detoxifying the Cd body burden from the test tissues. PMID- 26862255 TI - Preclinical Safety Assessment of Standardized Extract of Centella asiatica (L.) Urban Leaves. AB - CONTEXT: Centella asiatica (CA) leaves extract has been shown therapeutic potential. However, safety information is lacking. AIMS: To evaluate acute oral toxicity (AOT), sub-chronic toxicity, and mutagenic potential of standardized extract of CA (L.) Urban leaves (INDCA). MATERIALS AND METHODS: For the acute toxicity study, INDCA was orally administered to Sprague-Dawley rats at a dose range of 0-2000 mg/kg. For the repeated dose toxicity study, the rats of either sex were orally administered with INDCA at the doses of 250, 500, and 1000 mg/kg/day for a period of 90 days. The effects on body weight, food and water consumption, organ weight, hematology, clinical chemistry as well as histology were studied. The mutagenic potential of INDCA was tested using reverse mutation assay (Ames test). STATISTICAL ANALYSIS USED: Data of each parameter were analyzed by one-way ANOVA followed by Dunnett's test to compare the difference between treated groups. RESULTS: The administration of INDCA did not produce mortality or significant changes in the clinical signs included but not limited to changes in the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavior pattern. The appearance, progress, and disappearance of these signs were recorded. The lethal dose and no observable adverse effect level of INDCA were 2000 mg/kg and 1000 mg/kg, respectively. There were no significant differences in the organ weights, hematological parameters, clinical chemistry values, or gross and microscopic appearance of the organs from the treatment groups as compared to the control group. It was found to be nonmutagenic in reverse mutation assay. CONCLUSIONS: INDCA was found safe in AOT, sub-chronic toxicity, and mutagenicity studies when tested in rats. PMID- 26862256 TI - Terminalia Chebula Attenuates DMBA/Croton Oil-Induced Oxidative Stress and Inflammation in Swiss albino Mouse Skin. AB - OBJECTIVE: The present study was designed to investigate underlying molecular mechanism for antitumorigenic potential of Terminalia chebula (TC) against chemically-induced skin tumorigenesis in Swiss albino mice. It is used as herbal medicine because it exhibits antioxidant, anti-inflammatory, and anticarcinogenic activity. However, the precised underlying mechanism remains to be elucidated. MATERIALS AND METHODS: In light of the important role of nuclear factor-kappaB (NF-kappaB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (i-NOS), ornithine decarboxylase (ODC), proinflammatory cytokines, oxidative stress in carcinogenesis, chemopreventive efficacy of TC against 7,12-dimethylbenz[a] anthracene (DMBA), and croton oil-induced 2-stage skin carcinogenesis was studied in terms of cytoprotective antioxidant enzymes activity, lipid peroxidation (LPO), inflammatory responses, and expression of various molecular markers in skin tissues. RESULTS: We found that topical application of TC at dose of 30 mg/kg b. wt. mouse effectively suppressed oxidative stress and deregulated activation of inflammatory mediators and tumorigenesis. Histological findings further supported the protective effects of TC against DMBA/croton oil-induced cutaneous damage. CONCLUSION: The findings of the present study suggest that the chemopreventive effect of TC is associated with upregulation of endogenous cytoprotective machinery and downregulation of inflammatory mediators (interleukin (IL)-6, COX-2, i-NOS, ODC, and NF-kappaB). PMID- 26862258 TI - Beneficial Effects of Emblica officinalis on Fluoride-induced Toxicity on Brain Biochemical Indexes and Learning-memory in Rats. AB - AIMS: The present study was aimed to investigate the effects of Emblica officinalis against fluoride-induced alterations in the behavioral and biochemical abnormalities in rats. DESIGN: The healthy adult albino rats of Wistar strain (Rattus norvegicus) weighed 200-250 g were used for experiments. The animals were divided into three groups. Group I, control rats received only drinking water (F 0.9 ppm). Group II rats were exposed to fluoride (10 ppm) water for 60 days. Group III rats were treated with E. officinalis (100 mg/day/rat) along with fluoride water for 60 days. In order to investigate the effects of elevated levels of fluoride (10 ppm) in drinking water on behavioral pattern of rat, a maze test was carried out in all three groups from day 1 till completion of treatment. MATERIALS AND METHODS: The animals were weighed before and after treatment. After respective treatment, the animals were autopsied. The blood was collected through cardiac puncture and brain was excised blotted free of blood weighed and used for biochemical parameters. The estimation of protein, enzyme activity of cholinesterase (ChE), and lipid peroxidation were carried out in brain using standard techniques. RESULTS: The tissue (brain) and serum fluoride was estimated by a fluoride-specific electrode (Orion). Learning and memory abilities assessed during maze test showed reduced memory retention in rats exposed to fluoride water in comparison to control whereas amla powder (E. officinalis) fed rats showed increased memory retention than fluoride water exposed rats. The protein content and ChE enzyme activity in brain of fluoride exposed rats diminished as compared to control whereas the same was found to be elevated in E. officinalis fed rats. The level of malanoaldehyde showed a significant increase in fluoride-treated group and decrease in E. officinalis treated group. CONCLUSIONS: Our results suggest that exposure of rats to Na-F has detrimental effects on the brain as reflected in diminished learning and memory. Administration of E. officinalis during fluoride exposure significantly overcome neuronal fluoride toxicity and, therefore, may be used as a therapeutic agent for fluorotic victims. PMID- 26862257 TI - Paraquat Poisoning: Analysis of an Uncommon Cause of Fatal Poisoning from Manipal, South India. AB - BACKGROUND: Morbidity and mortality related to acute poisoning is a serious health concern worldwide. Paraquat is known to be responsible for a number of acute poisonings in south India. AIM: The study aims at presenting the various aspects of paraquat poisoning that include patient profile, clinical presentation, end-organ complications, and observations at autopsy. MATERIALS AND METHODS: The present registry-based retrospective research was conducted in a tertiary care teaching hospital in south India. All the confirmed cases of paraquat poisoning were included in the present study. The postmortem and hospital records of these patients were retrieved and relevant information was collected and analyzed. RESULTS: Paraquat poisonings constituted 14.4% of the total poisoning fatalities during the study period. Equal number of males and females were observed in the present study. The victims were aged between 17 and 65 years (mean +/- SD = 30.2 +/- 13.1 years). Manner of death was suicidal in 92.9% cases. Common presenting symptoms after ingestion of paraquat included vomiting, followed by difficulty in breathing. In the present series, overall survival post paraquat consumption ranged between 10 h and 25 days. Half of the victims died within 2 days of consumption of poison. The underlying cause of death included acute renal failure (ARF), adult respiratory distress syndrome (ARDS), multiorgan failure (MOF), acute liver failure, etc., In all the cases, brain was congested and edematous, and visceral organs showed marked congestion at autopsy. Lungs were congested with marked edema in 10 cases. CONCLUSION: It is recommended that the availability of this highly toxic substance be restricted so as to prevent its misuse as a method of suicide. PMID- 26862259 TI - N-acetylcysteine, Ascorbic Acid, and Methylene Blue for the Treatment of Aluminium Phosphide Poisoning: Still Beneficial? AB - OBJECTIVES: Intentional and accidental intoxication with aluminium phosphide (ALP) remains a clinical problem, especially in the Middle East region. Considering the high mortality rate besides lack of any recommended first option drug for its treatment, this study was aimed to compare the therapeutic effects of N-acetylcysteine (NAC), vitamin C (Vit C), and methylene blue; both in isolate and also in combination, for the treatment of ALP intoxication in a rat model. MATERIALS AND METHODS: In this experimental animal study, 80 male Wistar rats in eight groups were intoxicated with ALP (12.5 mg/kg) and treated with a single dose of NAC (100 mg/kg) or Vit C (500-1,000 mg/kg) or methylene blue (1 mg/kg/5 min, 0.1%) or two of these agents or all three of them (controls were not treated). Rats were monitored regarding the parameters of drug efficacy as increased survival time and reduced morbidity and mortality rate for 3 consecutive days to ensure toxin neutralization. Macroscopic changes were recorded and biopsy sections were taken from brain, cerebellum, kidney, liver, and heart for microscopic evaluation regarding cellular hypoxia. RESULTS: The mean survival times of rats exposed to ALP and treated with VitC + NAC was 210.55+/-236.22 minutes. In analysis of survival times, there was a significant difference between Group 5 which received VitC + NAC and the other groups (P < 0.01). Serum magnesium levels after death were higher than normal (P = 0.01). CONCLUSIONS: Despite the higher survival rate of antioxidant-treated rats compared with controls, this difference was not statistically significant. PMID- 26862260 TI - Impact of Organic Contamination on Some Aquatic Organisms. AB - BACKGROUND: Contamination of water systems with organic compounds of agricultural uses pose threats to aquatic organisms. Carbaryl, chlorpyrifos, and diuron were considered as model aquatic pollutants in this study. The main objective of this study was to characterize the toxicity of organic contamination to two different aquatic organisms. MATERIALS AND METHODS: Low concentrations (0.0-60 umol/L) of carbaryl, diuron and very low concentration (0.0-0.14 umol/L) of chlorpyrifos and their mixtures were tested against fish and Daphnia magna. Percentage of death and immobilization were taken as indicators of toxicity. RESULTS: Toxicity results to fish and D. magna showed that chlorpyrifos was the most toxic compound (LC50 to fish and D. magna are 0.08, and 0.001 umol/L respectively), followed by carbaryl (LC50 to fish and D. magna are 43.19 and 0.031 umol/L), while diuron was the least toxic one (LC50 values for fish and D. magna are 43.48 and 32.11 umol/L respectively). Mixture toxicity (binary and tertiary mixtures) showed antagonistic effects. Statistical analysis showed a significant difference among mixture toxicities to fish and D. magma. CONCLUSION: Fish and D. magam were sensitive to low concentrations. These data suggest potent threats to aquatic organisms from organic contamination. PMID- 26862261 TI - Assessment of Antioxidant Potential and Acute Toxicity Studies of Whole Plant Extract of Pergularia Daemia (Forsk). AB - BACKGROUND: Pergularia daemia (Asclepiadacea) is a fetid- smelling perennial herb growing well along the river bang and road sides of India. Naturally the plant has powerful antioxidants including polyphenols, flavanoids, steroids and terpenoids. OBJECTIVE: The aim of this study is to evaluate the in vitro antioxidant potential and to determine the median lethal dose (LD50) of crude ethyl acetate and methanol extracts of Pergularia daemia. The plant Pergularia daemia possess effective scavenging activity against 2, 2' azino bis (3 ethylbenzothiazoline 6 sulfonic acid (ABTS), nitric oxide and reducing power radicals at different concentrations (100, 200, 300, 400 & 500 ug/mL) of both extracts. RESULTS: From the above in vitro assay we have exposed that the methanolic extract exert higher antioxidant activity at 400 ug/mL than ethyl acetate extract. Acute toxicity study revealed that the extracts showed no signs of toxicity upto a dose level of 2500 mg/kg b.wt. CONCLUSION: Thus our findings provide that both extracts of Pergularia daemia possess a strong antioxidant capacity and are relatively has high margin of safety. PMID- 26862262 TI - Evaluation of Toxicity Effects of Asafetida on Biochemical, Hematological, and Histological Parameters in Male Wistar Rats. AB - OBJECTIVES: Asafetida is traditionally used in folklore medicine for the treatment of various ailments. To validate its use in traditional medicine, it is important to evaluate its toxicity in the animal system. Therefore, this study aimed to evaluate the toxicological effects of asafetida in Wistar albino rats. MATERIALS AND METHODS: Acute toxicity tests were conducted by the oral administration of 250, 500, and 1,000 mg/kg body weight of the animal. In chronic study, animals were administered with various doses of asafetida (25, 50, 100, and 200 mg/kg body weight) for a period of 6 weeks. At end of experiment, the effects of asafetida on hematological, renal, and hepatic markers and histological parameters were analyzed. RESULTS: In acute toxicity study, no mortality was seen up to 72 h of the administration of asafetida. No signs of neurological and behavioral changes were noticed within 24 h. In the chronic study, the asafetida intake has changed the hematological parameters such as red blood cell (RBC), white blood cell (WBC), hematocrit (HCT), and platelets. Aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were significantly increased in treated animals. The plasma level of urea and creatinine were not altered by the administration of asafetida throughout the study. Histopathology study indicates hepatotoxicity, but no signs of prominent pathological changes in kidney. CONCLUSIONS: Asafetida did not show any acute toxicity, but chronic administration could have undesirable effects on hepatocytes and hematological factors. PMID- 26862264 TI - Oxidative Stress Biomarkers in the Freshwater Fish, Heteropneustes fossilis (Bloch) Exposed to Sodium Fluoride: Antioxidant Defense and Role of Ascorbic Acid. AB - The present study highlights fluoride -induced toxicity and the protective role of ascorbic acid in the liver and ovary of freshwater fish, Heteropneustis fossilis. The fish specimens were exposed to different concentrations (35 mg F/L and 70 mg F/L) of fluoride. Parameters related to oxidative stress were studied at the end of the experiment. The biomarkers selected for the study were thiobarbituric acid reactive substances for assessing the extent of lipid peroxidation (LPO) and antioxidant defense system such as reduced glutathione (GSH), superoxide dismutase (SOD) catalase (CAT) glutathione peroxidase (GPx), and glutathione S-transferase (GST) activities. The fluoride exposure significantly elevated the level of LPO, CAT, SOD, and GST in the tissues of treated group as well as modulated the activities of GSH and level of GPx after exposure as compared to the control. A significant decrease in GPx activity was found in these tissues suggesting that fluoride exposure increases the level of free radical, as well as CAT activity. Pre- and post treatment with ascorbic acid decreased the LPO, SOD, CAT, GST level, and increased GSH, GPx levels in the liver and ovary. PMID- 26862263 TI - Clinico-Epidemiological Profile of Snakebite Cases Admitted in a Tertiary Care Centre in South India: A 5 Years Study. AB - OBJECTIVES: This study was conducted to assess the clinic-epidemiological profile of snakebite cases admitted at a Tertiary Care Centre in South India. MATERIALS AND METHODS: A record based retrospective study was carried out at Kasturbha Medical College affiliated hospitals in Mangalore. All the snakebite cases admitted to the hospitals from January 2007 to December 2011 were included in the study. Data were collected using a pretested semi-structured questionnaire and analyzed using Statistical Package for Social Sciences (SPSS version 11.5). The results are expressed as percentages. RESULTS: The study included 198 cases of snakebite victims. The majority of the cases were males (68.2%). The mean age of the study population was 34.8 years. Maximum numbers of snakebite cases were reported during the month of September to December (47.9%). The peak time of snakebite was between 18.01 and 24.00 h which was reported in 40.5% of the cases. Lower extremities were the most common site of bite in more than three-fourth of the cases (80.9%). The most common symptoms were a pain (45.9%) and swelling (44.9%). The case fatality rate was observed to be 3.0%. CONCLUSION: Snakebite still remains a major public health problem in this part of the world. Knowledge must be imparted regarding the prevention of snakebites through community health programs. Messages regarding prompt reporting of such cases and importance of effective treatment must be disseminated among people through mass media and role plays. PMID- 26862265 TI - Clinico-epidemiological Profile of Snake Bites over 6-year Period from a Rural Secondary Care Centre of Northern India: A Descriptive Study. AB - Estimated deaths due to snake bites are more than 46,000 annually in India. Ninety-seven percent bites occur in rural areas. Data on snake bites from Jharkhand rural area are sparse. This study describes 6 years profile of snake bite patients from January, 2007 to December, 2012 at Nav Jivan Hospital in Palamu district, Jharkhand. PMID- 26862266 TI - Dose Dependent Effect of Iso-Octane on HaCaT: A Model Study. AB - OBJECTIVE: Improved understanding of cytotoxicity under chemical assaults may be achieved by multimodal analysis of cellular morphology, viability, molecular expressions, and biophysical properties. MATERIALS AND METHODS: In this study dose-dependent effects of an organic solvent (OS), iso-octane (IO), known to cause skin irritation, has been explored multimodally for understanding its effect on structural and functional profile of normal epithelial cell population in vitro. RESULTS: Under IO exposures, after 5 h there was a sharp decrease in viability of HaCaT with increasing doses which may be due to disruption in cellular association noted via immunocytochemical study and was further supported by the decreased expression of E-cadherin at transcriptomic level. Dislocation of E-cadherin from membrane to the cytoplasm occurred with increasing doses. The dose-dependent changes in varied aspects of bioelectrical properties, having plausible correlation with cellular viability, association, and adherence were noteworthy at 5 h of IO exposure. Evaluation of biomechanical properties by micropipette aspiration showed a distinct change in cellular stiffness in terms of increase in suction force and post-suction alteration in cellular shape. The cells became stiffer and fragile with increasing IO doses. CONCLUSION: Present study explicated dose-dependent cytotoxicity of IO on HaCaT and explored the usefulness of this approach to develop in vitro model system to evaluate epithelial toxicity with level-free markers. PMID- 26862267 TI - Protective Effects of Propofol Against Methamphetamine-induced Neurotoxicity. AB - CONTEXT: Methamphetamine (METH) is widely abused in worldwide. METH use could damage the dopaminergic system and induce neurotoxicity via oxidative stress and mitochondrial dysfunction. Propofol, a sedative-hypnotic agent, is known for its antioxidant properties. In this study, we used propofol for attenuating of METH induced neurotoxicity in rats. SUBJECTS AND METHODS: We used Wistar rats that the groups (six rats each group) were as follows: Control, METH (5 mg/kg IP), and propofol (5, 10 and 20 mg/kg, IP) was administered 30 min before METH. After 24 h, animals were killed, brain tissue was separated and the mitochondrial fraction was isolated, and oxidative stress markers were measured. RESULTS: Our results showed that METH significantly increased oxidative stress markers such as lipid peroxidation, reactive oxygen species formation and glutathione oxidation in the brain, and isolated mitochondria. Propofol significantly inhibited METH-induced oxidative stress in the brain and isolated mitochondria. Mitochondrial function decreased dramatically after METH administration that propofol pretreatment significantly improved mitochondrial function. Mitochondrial swelling and catalase activity also increased after METH exposure but was significantly decreased with propofol pretreatment. CONCLUSIONS: These results suggest that propofol prevented METH-induced oxidative stress and mitochondrial dysfunction and subsequently METH-induced neurotoxicity. Therefore, the effectiveness of this antioxidant should be evaluated for the treatment of METH toxicity and neurodegenerative disease. PMID- 26862268 TI - Effect of Cypermethrin on the Growth of Ciliate Protozoan Paramecium caudatum. AB - OBJECTIVE: The objective of this study is to assess the effect of cypermethrin on the growth of ciliate protozoan Paramecium caudatum. MATERIALS AND METHODS: Monoxenic culture of P. caudatum, were exposed to different doses (0.01, 0.05, 0.1, 0.15, and 0.2 ug/L) of cypermethrin along with control for 24, 48, 72, and 96 h time interval. The total numbers of live and dead cells were counted after trypan blue staining in Neubauer hemocytometer. RESULTS: Marked decrease in the number of living cells with the increase in the concentration of cypermethrin and with increasing exposure time intervals was recorded. CONCLUSION: The results indicate that cypermethrin is toxic to P. caudatum even at low concentrations when it enters in the aquatic system through runoff. PMID- 26862270 TI - Effect of Repeated Administration of Cefquinome on Biochemical and Hematological Parameters in Buffalo Calves. AB - AIM: Cefquinome, a fourth generation of cephalosporins have been developed for use in animals. Similar to other species, it may also have some adverse reactions in buffalo calves at therapeutic dosage. In the present study, effect of repeated administration of cefquinome on biochemical and hematological parameters was studied in buffalo calves. MATERIALS AND METHODS: Animals were divided into two groups having three animals in each group. Group 1 was kept as control and animals of Group 2 were given cefquinome at dose rate of 2 mg.kg(-1) body weight by intramuscular route for continuously 7 days. Blood samples were collected daily and 3 days post treatment. RESULTS: The values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGTP), and alkaline phosphatase (ALKP) in control animals were in the range of 127.7-148.3 IU/L,49.0-55.6 IU/L, 14.0-17.3 IU/L, and 111.0-134.3 IU/L, respectively. The repeated administration of cefquinome did not influence the plasma activities of AST, ALT, GGTP, and ALKP in treated animals. The level of blood urea nitrogen (BUN) and creatinine before treatment was 14.3 +/- 0.88 mg/dl and1.70 +/- 0.04 mg/dl, which significantly increased on 3(rd) day (21.0 +/ 1.53 mg/dl) and 2(nd) day (2.33 +/- 0.07 mg/dl), respectively. Among hematological parameters, there was significant variation in levels of hemoglobin (Hb), total erythrocyte count (TEC), erythrocyte sedimentation rate (ESR), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) in treated animals. No abnormal clinical symptoms were observed in any animal. CONCLUSION: The results revealed that clinically, the therapy of cefquinome may be continued up to 7 days. PMID- 26862269 TI - A Multidisciplinary Approach with Hyperbaric Oxygen Therapy Improve Outcome in Snake Bite Injuries. AB - AIM: Snakebite injuries are common in tropical India among those who are involved in outdoor activities. These injuries results in cellulitis, gangrene at the bite area, bleeding manifestations, compartment syndrome, regional lymphadenopathy, septicemia, hypotension, and disseminated intravascular coagulation (DIC) resulting in significant morbidity and mortality. The purpose of this study is to share our experience of multidisciplinary approach in the management of snakebite injuries of the extremities with various treatment modalities including hyperbaric oxygen (HBO) therapy, surgical debridement, and soft tissue reconstruction to provide an effective treatment for snake bite injuries. METHODS: The study was conducted in the Department of Plastic Surgery, during the period October 2012-December 2014, wherein all the patients who were admitted with snakebite injuries were enrolled and the patients treated in plastic surgery department were included into the study. Out of total 766 patients, there were 323 patients treated with anti snake venom (ASV) and 29 died among the treated patients; 205 patients belonged to pediatric age group. RESULTS: Out of 112 patients referred to Department of Plastic Surgery, 50 cases presented with cellulitis, 24 patients with compartment syndrome, and 38 patients were referred for the management of soft tissue cover over the extremities. Among 112 patients, 77 involved the lower extremity and 35 the upper extremity. CONCLUSION: Multidisciplinary approach including hyperbaric oxygen (HBO) therapy improves outcome in the management of snakebite injuries of the extremities. PMID- 26862272 TI - A Three Generation Study with Effect of Imidacloprid in Rats: Biochemical and Histopathological Investigation. AB - OBJECTIVES: This study was designed to evaluate the dose-dependent toxic effects of imidacloprid on the female ratsthat were treated through three generations (F0, F1, and F2). F2 female rats were sacrificed at the end of the experiment to see the long-term effect of imidacloprid. MATERIALS AND METHODS: Rats were divided into three groups of 6 each. Group I served as control. Group II served as treated I and given 1/45(th) LD50 (10 mg/kg/day) of imidacloprid. Group III served as treated II and given 1/22(th) LD50 (20 mg/kg/day) of imidacloprid. After 60 days, oral administration of imidacloprid females were mated with normal males to get F1 and F2 generation. F2 generation female rats were sacrificed at the end of the experiment. Biochemical and a histopathological investigation was done for three groups of F2 generation and statistically analyzed by ANOVA. RESULTS: Average feed intake of F2 female rats was significantly reduced (P < 0.01) at 20 mg/kg/day dose of imidacloprid. There was a significant increase in the activity of alanine aminotransferase, AKP, and glucose 6-phosphate dehydrogenase in Group III rats of F2 generation. There was a significant decrease in acetylcholine esterase activity in plasma and brain of both the imidacloprid treated groups. Tissue samples of liver, kidney, and brain of females of F2 generation showed histopathological condition. CONCLUSION: The results indicated that imidacloprid at a dose of 20 mg/kg bw/day exerts significant toxicological effects on biochemical and histological studies of F2 generation females as compare to 10 mg/kg bw/day. PMID- 26862271 TI - Assessment of Anticarcinogenic Potential of Vitex trifolia and Triticum aestivum Linn by In Vitro Rat Liver Microsomal Degranulation. AB - OBJECTIVE: The main objective of this preliminary study is to confirm the synergistic anticarcinogenic potential of Vitex trifolia and Triticum aestivum ethanolic extracts. MATERIALS AND METHODS: Rat hepatic microsomal degranulation is a short - term technique that has been used for the detection of potential chemical carcinogens, in vitro. The present study has been carried out to study the inhibition of ribosome- membrane disruption against 3, 8-Diamino-5-ethyl-6 pheylphenanthridinium bromide (EB), as the degranulating agent, by measuring the RNA/protein ratios of microsomal membranes in the presence or absence of V.trifolia and T. aestivum extracts. These two extracts were further evaluated for cytotoxic effect in HCT 116 and A549 cell lines. RESULTS: V. trifolia and T. aestivum protects hepatic microsomes against the degranulatory attack by the carcinogen EB showed a significant reduction in the proliferation of the HCT 116 and A549 cancer cell lines. CONCLUSION: The ethanolic extracts of the plants, V. trifolia and T. aestivum individually possessed anti-degranulatory potential. Importantly they act synergistically, possess appreciable anticarcinogenic properties, based on their ability to inhibit EB induced liver microsomal degranulation. Further these extracts inhibit cell proliferation of cancer cell lines. PMID- 26862273 TI - Detection of Malathion Resistance in Hyalomma anatolicum anatolicum from Bathinda District, Punjab. AB - OBJECTIVE: The resistance status against malathion in Hyalomma anatolicum anatolicum ticks collected from Bathinda district, Punjab, was evaluated by adult immersion test (AIT). MATERIALS AND METHODS: Technical grade malathion was used for conduction of AIT with 2 min immersion time protocol. The regression graph of probit mortality of ticks was plotted against log values of increasing concentrations of malathion and was utilized for the determination of slope of mortality, LC50, LC95 (95% confidence interval [CI]) and resistance factor (RF). The reproductive parameters of treated ticks viz. egg mass weight, reproductive index (RI), and percentage inhibition of oviposition (% IO) were also studied. RESULTS: The increasing concentration of malathion showed an upward trend in per cent tick mortality. The slope of mortality (95% CI) was 2.489 +/- 0.719 (2.489 +/- 0.719) and value of goodness of fit (R(2)) was 0.799. The LC50 (95% CI) and LC95 (95% CI) values were recorded as 9099.2 (8378.6-9881.7) and 41,511.3 (35,060.2-49,149.4) ppm, respectively, with RF as 16.60 indicating level II resistance status. A negative dose-dependent slope of egg mass weight (-91.79 +/- 25.15 [-171.8 to -11.76]) was recorded as the survived ticks laid significantly (P = 0.0355) fewer eggs. The mean RI of treated ticks decreased with increasing concentrations of drug and the slope (95% CI) was -0.293 +/- 0.059 (-0.482 to 0.105). Further, a dose-dependent significant increase (P = 0.0157) in the mean % IO was recorded in treated ticks. CONCLUSIONS: The results of the current study would be useful in the formulation and implementation of effective tick strategies in the region. PMID- 26862275 TI - Anti-arthritic Activity of Dashanga Ghana (An Ayurvedic Compound Formulation) Against Freund's Adjuvant Induced Arthritis in Charles Foster Albino Rats. AB - INTRODUCTION: Arthritis is the most common cause of disability, limiting the activities of adults throughout the world. Apart from the conventional treatment strategies using non-steroidal anti-inflammatory drugs, disease-modifying anti rheumatic drugs, and glucocorticoids, newer and safer drugs are continuously being searched, as long-term usage of these drugs have resulted in adverse effects. Besides this, currently a number of medicinal plants are under scientific evaluation to develop a promising remedy in these cases. There is a need to investigate the complete therapeutic potential of these herbals for providing newer and safer treatment options with minimum side effects. Considering this, a polyherbal Ayurvedic compound formulation (Dashanga Ghana) has been studied in experimental animals to evaluate anti-arthritic activity. MATERIALS AND METHODS: Dashanga Ghana has been prepared in the laboratory by following standard guidelines. Charles Foster albino rats were used to evaluate the activity through Freund's adjuvant induced arthritis model. RESULTS AND CONCLUSIONS: Dashanga Ghana is found to possess significant anti-arthritic activity. Further studies are required to identify and characterize exact active phyto-constituents and to elucidate the exact mechanism of action, which is responsible for the observed pharmacological profile. PMID- 26862276 TI - Alterations in Hematological Profile of Experimentally Induced Subchronic Thiacloprid Toxicosis in Gallus domesticus. AB - OBJECTIVES: Thiacloprid, a novel neonicotinoid insecticide is chiefly used as a crop protectant therefore it is likely to cause indirect exposure to poultry through contaminated feed and water because this species is occasionally supplied with feed that is, declared unfit for human consumption. The current study was performed to explore the nonlethal toxic effects of thiacloprid in Gallus domesticus on hematological parameters. MATERIALS AND METHODS: Fifty-two birds were randomly divided into nine groups. Groups I to IV of four birds each were kept as healthy control. The Groups V, VI, VII, VIII, IX, and X contained six birds each and were administered thiacloprid at 1 mg/kg/day for 15, 30, 45, 60, 75, and 90 days, respectively. RESULTS: Thiacloprid caused variable changes in the hematological parameters. There was a significant decline in the packed cell volume (PCV), hemoglobin (Hb) concentration, and total erythrocyte count (TEC). The PCV declined to the extent of 23.33 +/- 0.76% on day 90 from the 0 day value of 29.75 +/- 1.26% of experiment. The Hb concentration decreased from 9.93 +/- 0.57 g/dl (0 day) to 7.52 +/- 0.62 g/dl (90 days). The TEC declined from the 0 day value of 2.41 +/- 0.08 * 10(6)/mm(3) to 90 days value of 2.08 +/- 0.05 * 10(6)/mm(3). The total leukocyte count on 0 day was 12.50 +/- 0.76 * 10(3)/mm(3) and it showed a significant increase from day 45 (17.80 +/- 2.67 * 10(3)/mm(3)) to day 90 (21.33 +/- 1.48 * 10(3)/mm(3)) of thiacloprid treatment. There was a significant rise in value of erythrocyte sedimentation rate to 19.25 +/- 1.22 mm/24 h on day 90 of treatment from the 14.42 +/- 1.09 mm/24 h on 0 day. The long term oral administration of thiacloprid produced no significant alterations in the values of erythrocytic indices. CONCLUSIONS: The repeated oral toxicity on thiacloprid in present investigation suggested that it has an adverse effect on health of birds and is moderately risk insecticide in G. domesticus. PMID- 26862277 TI - Food Color Induced Hepatotoxicity in Swiss Albino Rats, Rattus norvegicus. AB - OBJECTIVE: Certain dietary constituents can induce toxicity and play a critical role in the development of several hepatic disorders. Tartrazine, metanil yellow and sunset yellow are widely used azo dyes in food products, so the present study is aimed to investigate the food color induced hepatotoxicity in Swiss albino rats. MATERIALS AND METHODS: Swiss albino rats were divided into four groups, each group having six animals. Group I served as control, Group II, Group III and Group IV were administered with 25, 50 and 75 mg/kg body weight blend of sunset yellow, metanil yellow and tartrazine for 30 days. Hepatotoxicity in rats treated with a blend of these food colors was studied by assessing parameters such as serum total protein, serum albumin, serum alkaline phosphatase (ALP) as well as hepatic malondialdehyde (MDA). The activity of superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) were assessed. RESULTS: Significantly increased concentrations of serum total protein, serum albumin, serum ALP and hepatic MDA and significantly lowered levels of SOD, reduced GSH and CAT in the liver tissue of treated animals were observed when compared with control animals. The alteration in the liver includes necrosis of hepatocytes, infiltration and vacuolation. CONCLUSION: The result indicates that consumption of food color in diet induces liver tissue damage. The used doses of food color were mostly attributable to hepatocellular damage and drastic alteration in antioxidant defense system. PMID- 26862278 TI - A case of Trientine Overdose. AB - Wilson disease is a rare genetic hepatic and neurological disorder of copper accumulation. Trientine is usually used as a second line in the management of patients with this condition. We present a case of a large overdose of Trientine (60 g) resulting in self-limiting dizziness and vomiting with no further clinical sequelae or significant biochemical abnormalities. This case shows that Trientine has a good safety profile and hence could be used as a first line treatment in patients with Wilson's disease who suffer from psychiatric complications and who might be at risk of self-harm. PMID- 26862274 TI - Modulating Effect of Enicostemma littorale on the Expression Pattern of Apoptotic, Cell Proliferative, Inflammatory and Angiogenic Markers During 7, 12 Dimethylbenz (a) Anthracene Induced Hamster Buccal Pouch Carcinogenesis. AB - Enicostemma littorale leaves are traditionally used for the treatment of several diseases, including inflammation and cancer. This study has taken effort to explore the antitumor initiating potential of E. littorale leaves (ElELet) by analyzing the expression pattern of apoptotic (p53, Bcl-2 and Bcl-2 associated X protein), cell-proliferative (cyclin D1 and proliferating cell nuclear antigen), angiogenic (vascular endothelial growth factor), invasive (matrix metalloproteinase-2 and 9), and inflammatory (NF-kappaB and cyclooxygenase-2) markers during 7, 12-dimethylbenz (a) anthracene (DMBA) induced hamster buccal pouch carcinogenesis. Oral tumors were induced in the buccal pouches of hamsters using the potent site and organ specific carcinogen, DMBA. DMBA application 3 times a week for 14 weeks resulted in tumor formation in the buccal pouches. Hundred percent tumor formations with dysregulation in the expression pattern of apoptotic, cell proliferative, inflammatory, angiogenic, and invasive markers were observed in the buccal pouches of hamsters treated with DMBA alone. ElELet at a dose of 250 mg/kg body weight orally to DMBA treated hamsters significantly prevented the tumor formation as well as corrected the abnormalities in the expression pattern of above mentioned molecular markers. ElELet thus modulated the expression pattern of all the above mentioned molecular markers in favor of the suppression of cell proliferation occurring in DMBA induced hamster buccal pouch carcinogenesis. PMID- 26862280 TI - Bilateral Eyelid Ptosis, Attributed to Vincristine, Treated Successfully with Pyridoxine and Thiamine in a Child with Acute Lymphoblastic Leukemia. AB - Vincristine-induced neurotoxicity is an adverse effect commonly seen in pediatric patients treated for cancer. We hereby present a case of a 6-year-old boy with acute lymphoblastic leukemia, who developed bilateral eyelid ptosis 25 days after the last intravenous administration of vincristine (cumulative dose 14.2 mg i.e., 17.75 mg/m(2)). The boy was treated with 5 mg/kg thiamine and with 10 mg/kg pyridoxine. Complete recovery of ptosis was noticed 4 weeks after the initiation of Vitamins B1 and B6 supplementation therapy. PMID- 26862279 TI - Psychosis as Harbinger of Phenytoin Toxicity. AB - Psychosis with phenytoin use has earlier been reported only in the context of Vitamin B12 or folic acid deficiency. We report a rare case of phenytoin toxicity manifesting as psychosis in the absence of Vitamin deficiency. The importance of recognition of psychosis as a harbinger of phenytoin toxicity and implications for management are discussed. PMID- 26862281 TI - Fipronil Compound Consumption Presenting as Status Epilepticus. AB - Fipronil is a broadspectrum N-phenylpyrazole insecticide with gamma-aminobutyric acid type A receptor inhibitory action causing hyperexcitability of central nervous system. There is no literature reported in the past concerning its acute toxicity in human beings. A case report is useful for workers in medical and veterinary field. Hence, we are reporting a case in which young male intoxicated with fipronil compound was presented to the emergency department for having generalized tonic-clonic seizures and subsequently with the features of delirium for few days. This patient was treated with benzodiazepines which controlled the seizures and antipsychotics were given for few days for treating the psychosis. PMID- 26862282 TI - An Unsuspected Pharmacological Vitamin D Toxicity in a Child and its Brief Review of Literature. AB - Inordinate administration of Vitamin D beyond required doses and duration occurs as a sporadic event among frequent empirical therapies of pharmacological Vitamin D. Such instances lead to Vitamin D intoxication. Systemic hypertension is an unsuspected after-effect of Vitamin D toxicity in a child unlike other toxicity effects such as hypercalcemia, neurological deterioration, etc., Here, we report a case of a 1-year-old child who developed acute hypertension and severe hypercalcemia due to Vitamin D toxicity which was masked by initial dehydration such as illness and brief review of literature about clinical entity. PMID- 26862283 TI - Eucalyptus Oil Poisoning. PMID- 26862284 TI - An Unusual Case of Triazophos Poisoning Presenting with New-Onset Refractory Status Epilepticus. PMID- 26862285 TI - Indian Association of Pediatric Surgeons Golden Jubilee: The milestone and the signposts ahead. PMID- 26862286 TI - Pediatric airway endoscopy. PMID- 26862287 TI - Child health initiatives by pediatric surgeons foundation. PMID- 26862288 TI - A study of associated congenital anomalies with biliary atresia. AB - BACKGROUND/PURPOSE: This study aims to analyze the incidence and type of various associated anomalies among infants with extrahepatic biliary atresia (EHBA), compare their frequency with those quoted in the existing literature and assess their role in the overall management. MATERIALS AND METHODS: A retrospective study was performed on 137 infants who underwent the Kasai procedure for EHBA during the past 12 years. The medical records were reviewed for the incidence and type of associated anomalies in addition to the details of the management of the EHBA. RESULTS: Of the137 infants, 40 (29.2%) were diagnosed as having 58 anomalies. The majority of patients had presented in the 3(rd) month of life; mean age was 81 +/- 33 days (range = 20-150 days). There were 32 males and 8 females; boys with EHBA had a higher incidence of associated anomalies. Of these 40 patients, 22 (37.9%) had vascular anomalies, 13 patients (22.4%) had hernias (umbilical-10, inguinal-3), 7 patients (12.1%) had intestinal malrotation, 4 patients (6.8%) had choledochal cyst, 1 patient (1.7%) had Meckel's diverticulum, 3 patients (5%) had undergone prior treatment for jejunoileal atresias (jejunal 2, ileal-1), 2 patients (3.4%) had undergone prior treatment for esophageal atresia and tracheoesophageal fistula, 2 patients (3.4%) had spleniculi, and 2 patients (3.4%) were diagnosed as having situs inversus. CONCLUSIONS: The most common associated anomalies in our study were related to the vascular variation at the porta hepatis and the digestive system. The existence of anomalies in distantly developing anatomic regions in patients with EHBA supports the possibility of a "generalized" insult during embryogenesis rather than a "localized" defect. In addition, male infants were observed to have significantly more associated anomalies as compared with the female infants in contrast to earlier reports. PMID- 26862289 TI - Laparoscopic splenectomy in children with benign hematological diseases: Leaving nothing behind policy. AB - CONTEXT: Laparoscopic splenectomy (LS) is considered the standard approach for the treatment of children with nonmalignant hematological diseases due to the advances in the minimal invasive surgery over the conventional splenectomy (CS). Different techniques are involved in the operation to secure the hilum. AIM: The use of (LigasureTM) is a safe, effective, less time consuming and with less complications rate. MATERIALS AND METHODS: Sixty children (33 with thalassemia, 20 with immune thrombocytopenic purpura [ITP] and seven with spherocytosis) were operated during the period from June 2007 to December 2014. These children had undergone LS using (LigasureTM). Three ports were used in small-sized spleens while four ports were used in large spleens. RESULTS: There were 60 children (37 girls and 23 boys) with a mean age of 10.2 years had LS using LigasureTM with mean operative time of 85 min for cases of ITP and 120 min for other cases. There was no mortality. Two cases were converted to CS. CONCLUSIONS: Use of LigasureTM alone was safe, less time consuming with less complications rates. PMID- 26862290 TI - A functional study on small intestinal smooth muscles in jejunal atresia. AB - AIM: The present study was aimed to assess the contractile status of neonatal small intestinal smooth muscle of dilated pre-atretic part of intestinal atresia to resolve debatable issues related to mechanisms of persistent dysmotility after surgical repair. MATERIALS AND METHODS: A total of 34 longitudinally sectioned strips were prepared from pre-atretic dilated part of freshly excised 8 jejunal atresia type III a cases. Spontaneous as well as acetylcholine- and histamine induced contractions were recorded in vitro by using organ bath preparations. Chemically evoked contractions were further evaluated after application of atropine (muscarinic blocker), pheniramine (H1 blocker), and lignocaine (neuronal blocker) to ascertain receptors and neuronal involvement. Histological examinations of strips were made by using Masson trichrome stain to assess the fibrotic changes. RESULTS: All 34 strips, except four showed spontaneous contractions with mean frequency and amplitude of 5.49 +/- 0.26/min and 24.41 +/- 5.26 g/g wet tissue respectively. The response to ACh was nearly twice as compared to histamine for equimolar concentrations (100 MUM). ACh (100 MUM) induced contractions were attenuated (by 60%) by atropine. Histamine (100 MUM) induced contractions was blocked by pheniramine (0.32 MUM) and lignocaine (4 MUM) by 74% and 78%, respectively. Histopathological examination showed varying degree of fibrotic changes in muscle layers. CONCLUSIONS: Pre-atretic dilated part of jejunal atresia retains functional activity but with definitive histopathologic abnormalities. It is suggested that excision of a length of pre-atretic part and early stimulation of peristalsis by locally acting cholinomimetic or H1 agonist may help in reducing postoperative motility problems in atresia patients. PMID- 26862291 TI - Role of feeding jejunostomy in major anastomotic disruptions in esophageal atresia: A pilot study. AB - AIMS: To investigate the role of feeding jejunostomy (FJ) in patients of esophageal atresia with anastomotic leak (AL) to decrease the degree of gastroesophageal reflux (GER) and its effect on anastomotic healing. MATERIALS AND METHODS: Twenty neonates, with major AL and severe GER after primary repair were managed with decompressing gastrostomy and transgastric FJ and analyzed prospectively. RESULTS: Male to female ratio was 1.7:1. Mean birth weight was 2.2 kg. Anastomotic gap ranged from 0 to 4 cm. The amount of leak was more than 20% of nasogastric feeds. Gastrostomy and FJ was done on an average of the 12(th) postoperative day, after observing the general condition, chest tube output, lung expansion, and ventilatory requirement. There was a drastic reduction in chest tube output and lung expanded in all patients. Average hospital stay was 36 days (8-80 days). Sixty percentage patients were discharged successfully on FJ. Esophagogram demonstrated healing and leak free patency after an average of 1.5 months. GER was noted in seven patients, four developed stricture, and one had pseudodiverticulum in follow-up. CONCLUSION: Decompressing gastrostomy and FJ can be an alternative to managing major ALs. It helps in healing of anastomotic dehiscence and in preserving the native esophagus. PMID- 26862293 TI - Omental infarction: An unusual cause of right iliac fossa pain in children. AB - Omental infarction is an uncommon cause of acute abdomen in the pediatric population. We report a case of a 4-year-old male child with right iliac fossa pain. The final diagnosis was made on ultrasound and computed tomography findings. This entity needs to be differentiated from acute conditions like appendicitis, avoiding surgery. PMID- 26862292 TI - Bladder exstrophy-epispadias complex and the role of methylenetetrahydrofolate reductase C677T polymorphism: A case control study. AB - PURPOSE: The Bladder Exstrophy-Epispadias Complex (BEEC) is the most serious form of midline abdominal malformation. The etiology of BEEC is unknown and is thought to be multifactorial. Methylenetetrahydrofolate reductase (MTHFR) polymorphism C677T is strongly associated with other midline abnormalities such as neural tube defects. No proper case-control study existed comparing MTHFR polymorphism with BEEC. We sought to find an association with MTHFR polymorphism and patients with bladder exstrophy (BE). MATERIALS AND METHODS: The design of the study was a case control study, involving 50 children with BEEC and 50 normal healthy school children. Genetic analysis for MTHFR 677 polymorphism was carried out after DNA extraction and polymerase chain reaction amplification. Epidemiological analysis was done by using the birth defect questionnaire on parents of BEEC. RESULTS: Forty-two classical BE, two cloacal exstrophies (CE), four epispadias, and two exstrophy variant patients were a part of this study. Severe variety of BE had a significant association with C667T MTHFR polymorphism as compared to the normal control population (P = 0.01). CONCLUSION: C677T MTHFR polymorphism has a strong association with severe variety (CE) of BEEC occurrence. PMID- 26862294 TI - Dermoid cyst of an undescended intra-abdominal testis with torsion: A rare case report. AB - We report a case of dermoid cyst in an undescended intra-abdominal testis, which presented with torsion and gangrene. PMID- 26862295 TI - Congenital diaphragmatic hernia with recurrent gastric volvulus and pulmonary sequestration: A "chance" combination. AB - Congenital diaphragmatic hernia (CDH) is a known cause of secondary gastric volvulus. It is also known that bronchopulmonary sequestration (BPS) may be associated with CDH. An extremely rare case of BPS associated with gastric volvulus in a girl with left sided CDH is being reported. PMID- 26862296 TI - Reconstruction of a rare variant of the left hepatic vein in a left lateral segment liver graft from a living donor: Technical notes. AB - Reconstruction of hepatic veins in living donor liver transplantation (LDLT) is often technically challenging and a good venous outflow is essential for survival of the graft and patient. We describe a quadrangular patch venoplasty technique used for the reconstruction of a rare variant of the left hepatic vein (LHV) in a pediatric LDLT with left lateral segment (LLS) graft. Segment II vein in the graft was draining directly into the inferior vena cava (IVC) and segment III vein was draining into the middle hepatic vein (MHV) after receiving a tributary from segment IV so that there were two widely separated ostia at the cut surface. This is one of the rarest variations of the LHV and is so called type 3 variant; it is usually reconstructed using interposition tubular conduits necessitating two separate anastomoses at the IVC. PMID- 26862297 TI - Undescended testis and swelling in spigelian belt: Not always a spigelian hernia. PMID- 26862299 TI - Notice of Redundant Publication. PMID- 26862298 TI - Carbamylated Erythropoietin: A Prospective Drug Candidate for Neuroprotection. AB - Carbamylated erythropoietin (cEpo), which is neuroprotective but lacks hematopoietic activity, has been attracting rising concerns. However, the cellular and molecular mechanisms involved in the process of neuroprotection of cEpo are not well known. Based on several recent reports, the neuroprotective effects of cEpo are illustrated, and signaling pathways involved in the different effects of erythropoietin and cEpo are discussed. These newly reported researches may shed new light on the development and application of cEpo, a prospective drug candidate for neuroprotection. PMID- 26862300 TI - Assessment of Growth of Infants Fed an Amino Acid-Based Formula. AB - OBJECTIVE: This study's primary aim was to compare the growth (daily weight gain) of infants consuming a new (Test) amino acid-based formula (AAF) or a commercially available AAF (Control). METHODS: Healthy infants were randomized to Test or Control from 14 to 112 days of age. Anthropometric measurements were taken at 14, 28, 56, 84, and 112 days of age. Tolerance records were completed prior to each visit. Serum albumin and plasma amino acids were ascertained in a subset of infants at 84 days of age. RESULTS: A total of 119 subjects completed the study per protocol. Mean daily weight gains were 27.26 +/- 4.92 g/day for Control and 27.42 +/- 6.37 g/day for Test (P = 0.8812). There were no significant differences between groups in formula intake, adverse events, flatulence, spit up/vomiting, mood, or sleep. Albumin and plasma amino acids were within normal limits for both groups. CONCLUSIONS: Infants fed the new AAF had similar daily weight gains as infants fed a commercially available AAF. PMID- 26862301 TI - Secondary Advanced Abdominal Pregnancy after Suspected Ruptured Cornual Pregnancy with Good Maternal Outcome: A Case with Unusual Gangrenous Fetal Toes and Ultrasound Diagnoses Managed by Hysterectomy. AB - Incidence of abdominal pregnancy is accounting for 1.4% of all ectopic pregnancies. This is a rare case report of a 35-year-old multigravida who was presented to our hospital at 24 weeks of gestation with advanced live intraabdominal pregnancy diagnosed by ultrasound. The patient was followed up till 28 weeks in hospital for medicolegal viability in Egypt. Midline laparotomy was done, a live baby was delivered, and hysterectomy was done for attached placenta. Mother was discharged in good health, and baby was admitted in neonatal intensive care unit with no congenital anomalies and died after three weeks of sepsis. The management of advanced abdominal pregnancy remains controversial. Diagnosis and management of advanced abdominal pregnancy is still a challenge to today's medical world. But high index of suspicion aided with imaging studies can help in timely diagnosis, thereby preventing the associated life-threatening complications. PMID- 26862302 TI - Inhibition of adenovirus multiplication by inosine pranobex and interferon alpha in vitro. AB - There are no specific antivirals designed for adenoviral infections. Due to many cases of adenovirus infections worldwide, epidemic nature of some types of adenoviruses, and growing number of patients with severe adenoviral infections resulting from dysfunction the immune system, the need for searching an effective and safe therapy is increasing. Inosine pranobex exerts antiviral effects which are both direct and secondary to immunomodulatory activity. In the present study we evaluated in vitro effect of inosine pranobex and interferon alpha (IFN-alpha) on replication of HAdV-2 and HAdV-5. The effectiveness of inosine pranobex under these conditions has not been previously reported. In conducted study we reported that inosine pranobex reduced the titer of infectious HAdV-2 and HAdV-5 in vitro. Higher concentrations of IP strongly inhibited multiplication of viruses. Combination of inosine pranobex and IFN-alpha display higher efficacy than either treatment alone and suggest that both agents may increase therapeutic effectiveness without augmenting toxic effects. Combination index calculations showed that inosine pranobex and INF-alpha synergistically inhibit HAdV-2 and HAdV-5 titers in A549 cells. PMID- 26862303 TI - Evaluation of anti-inflammatory and analgesic activities of extracts from herb of Chelidonium majus L. AB - The aim of the study was to evaluate analgesic activity ("hot plate" test), anti inflammatory activity (carrageenan-induced paw edema) and locomotor activity in rats under the influence of three fractions of Chelidonium majus herb extract: full water extract (FWE), protein enriched fraction (PEF), and non-protein fraction (NPF). Effects of the fractions on the level of chosen cytokines and their mRNA levels were also assessed using lipopolysaccharide (LPS) administration as a proinflammatory cue. All fractions and diclofenac did not affect the locomotor activity of rats in comparison with the control group. FWE and PEF three hours after administration showed statistically significant analgesic activities comparable to morphine (p < 0.05). A slight reduction in rat paw edema was observed after three (comparable with diclofenac) and six hours in the NPF group. FWE revealed a statistically significant pro-inflammatory effect after three hours in comparison with the control group. Peripheral IL-1 and IL-4 cytokine concentrations were reduced under FWE and NPF, PEF fractions. The combination of FWE, PEF and NPF together with LPS showed only the effects of LPS. We suggest that protein enriched fraction (PEF) produced centrally mediated (morphine-like) analgesic action, whereas the anti-inflammatory potential was shown only after LPS-induced inflammation. The precise mechanisms involved in the production of anti-nociceptive and anti-inflammatory responses of studied fractions are not completely understood, but they may be caused rather by the presence of protein more than alkaloids-enriched fraction. This fraction of the extract could be used as an alternative therapy for the prevention of inflammatory-related diseases in the future, but further studies are needed. PMID- 26862304 TI - Matrine improves cognitive impairment and modulates the balance of Th17/Treg cytokines in a rat model of Abeta1-42-induced Alzheimer's disease. AB - Matrine (MAT) has been reported for its anti-inflammatory and neuroprotective effects. However, little is known about its effects on Th17/Treg cytokines and cognitive impairment in Alzheimer's disease (AD). In the present study, we injected Abeta 1-42 to the hippocampus of the rat to induce AD. Three groups of the AD rats were treated with MAT (25, 100 or 200 mg/kg/day, respectively) by intraperitoneal injection for 5 weeks. Levels of Th17 cell cytokines [interleukin (IL)-17A and IL-23] and regulatory T (Treg) cell cytokines [transforming growth factor beta (TGF-beta) and IL-35] in homogenates of the brain cortex and hippocampus were measured using enzyme-linked immunosorbent assay (ELISA) kits. The mRNA expressions of Th17 cell specific transcription factor RORgammat and Treg cell specific transcription factor Foxp3 in the brain cortex and hippocampus were quantified by real-time RT-PCR. Learning and memory ability of the rats were evaluated by Morris water maze test and novel object recognition test. ELISA detections showed the AD rats had increased levels of IL-17A and IL-23 as well as decreased levels of TGF-beta and IL-35. Matrine (100 and 200 mg/kg/day) significantly reversed the alternations of Th17/Treg cytokines induced by Abeta 1 42 injection, decreased RORgammat mRNA expression, increased Foxp3 mRNA expression and improved the learning and memory ability in the AD rats. The findings demonstrated that the AD rats had imbalance of Th17/Treg cytokines in the brain. MAT could dose-dependently restore the balance of Th17/Treg cytokines and attenuate the cognitive impairment in AD rats. PMID- 26862305 TI - Distinct effects of Lactobacillus plantarum KL30B and Escherichia coli 3A1 on the induction and development of acute and chronic inflammation. AB - OBJECTIVE: Enteric bacteria are involved in the pathogenesis of ulcerative colitis. In experimental colitis, a breakdown of the intestinal epithelial barrier results in inflow of various gut bacteria, induction of acute inflammation and finally, progression to chronic colitis. MATERIAL AND METHODS: In the present study we compared pro-inflammatory properties of two bacterial strains isolated from human microbiome, Escherichia coli 3A1 and Lactobacillus plantarum KL30B. The study was performed using two experimental models of acute inflammation: peritonitis in mice and trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. RESULTS: Both bacterial strains induced massive neutrophil infiltration upon injection into sterile peritoneal cavity. However, peritoneal exudate cells stimulated in vitro with E. coli 3A1, produced far more nitric oxide, than those stimulated with L. plantarum KL30B. Interestingly, distinct effect on the development of TNBS-induced colitis was observed after oral administration of the tested bacteria. Lactobacillus plantarum KL30B evoked strong acute colitis. On the contrary, the administration of E. coli 3A1 resulted in a progression of colitis to chronicity. CONCLUSIONS: Our results show that distinct effects of bacterial administration on the development of ongoing inflammation is strain specific and depends on the final effect of cross-talk between bacteria and cells of the innate immune system. PMID- 26862306 TI - A study on FoxP3 and Tregs in paired samples of peripheral blood and synovium in rheumatoid arthritis. AB - There is an increasing evidence suggesting the role of fork head boxP3 (FoxP3) in the development and the regulation of CD4(+)CD25(+) Treg cells. T-cell regulatory mechanisms in rheumatoid arthritis patients were evaluated by the contributing factors such as pro-inflammatory cytokines, circulating immune complexes, HLA DR expression, ligand binding biomarkers, FoxP3 expression in paired samples of peripheral blood (PB) and synovial fluid (SF). These cellular responses were further correlated with the humoral immune responses such as anti-cyclic citrullinated peptides IgG (CCP), circulating immune complex-c1q IgG (CIC), immunoglobulin G (IgG) and immunoglobulin M (IgM) of the rheumatoid arthritis factor (RAF). The results suggest a definitive role of Tregs in the homeostatic control because there is an increase in FoxP3 (37%) and HLA-DR (45%) expression in the synovial fluid as compared to PB. Furthermore, humoral responses as a downstream effector mechanism are positively correlated with the pathogenesis of rheumatoid arthritis (RA). A positive relationship exists between quantitative anti-CCP production and the expression of HLA-DR. The study relates an increased and pivotal role of B cell activation in the synovial fluid thereby permitting the need to ablate the targeted B cell immune responses. PMID- 26862307 TI - Contribution of the STAT4 rs7574865 gene polymorphism to the susceptibility to autoimmune thyroiditis in healthy Turk population and psoriatic subgroups. AB - INTRODUCTION: STAT4 is an important transcription factor that activates gene transcription as a response to cytokines. Recently, the influence of STAT4 gene on autoimmune disease has been widely studied in many different immune-related diseases. Autoimmune, metabolic and cardiovascular disorders are more common in psoriatic patients. STAT4 may be a unique gene that switches on in autoimmune related thyroid disease in psoriatic patients. THE AIM OF THE STUDY: To explore the association of a STAT4 rs7574865 polymorphism to autoimmune thyroid diseases in the general Turkish population and psoriatic subgroups. MATERIAL AND METHODS: A total of 132 psoriatic patients and 118 non-psoriatic volunteers were genotyped for STAT4 rs7574865 using real time PCR. Twenty-four of the psoriatic patients and 15 of the non-psoriatic volunteers have autoimmune-related thyroid diseases. RESULTS: The prevalence of the T allele [OR = 4.37; 95% CI: 1.05-19; p = 0.03] of the STAT4 rs7574865 was higher in individuals with autoimmune-related thyroid diseases among the all non-psoriatic volunteers. The volunteers with autoimmune related thyroid diseases has an increased allele positivity and carriers having at least one of the risk allele was significantly higher than in counterparts with a GG wild genotype [ORGT/TT vs. GG: 1.73; 95% CI: 0.09-32; p = 0.03]. Yet, there was no evidence of an association between rs7574865 and autoimmune-related thyroid disease in psoriatic patients. CONCLUSIONS: The STAT4 rs7574865 polymorphism increases autoimmune-related thyroid disease susceptibility among the general population but not in psoriatic patients. PMID- 26862308 TI - Ragweed-allergic subjects have decreased serum levels of chemokines CCL2, CCL3, CCL4 and CCL5 out of the pollen season. AB - CC-chemokines are important mediators of the allergic responses and regulate the cell trafficking. The aim of this study was to examine the serum levels of CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta and CCL5/RANTES, and to determine whether there are differences between ragweed-allergic subjects and healthy individuals out of the pollen season. Peripheral blood samples were collected from 24 subjects allergic to ragweed pollen and 12 healthy controls. Serum concentrations of chemokines/cytokines were measured by an enzyme-linked immunosorbent assay. We observed significantly decreased concentrations of CCL2/MCP-1, CCL3/MIP-1alpha, CCL4/MIP-1beta and CCL5/RANTES in the sera of ragweed-allergic patients compared to the healthy individuals (32.2 vs. 106.4 pg/ml, 89.5 vs. 135.7 pg/ml, 63.4 vs. 119.2 pg/ml and 11.2 vs. 18.1 ng/ml, respectively, p < 0.01). In contrast to the CC-chemokines, the serum levels of IL 8/CXCL8 showed a significant increase (p < 0.05) in the allergic group compared to the non-allergic subjects. Interleukin 4 levels were similar in both groups. In the sera of allergic patients, we have also detected significantly elevated levels of ragweed-specific IgE and IgG. However, decreased serum concentrations of the four CC-chemokines and elevated levels of IL-8/CXCL8 can be used as biomarkers for more accurate evaluation of the allergic status of patients with pollen allergy out of the season, to study the mechanisms for activation/inhibition of the subclinical allergic responses and for development of therapeutic strategies. PMID- 26862309 TI - Interleukin 18 and neutrophil-gelatinase associated lipocalin in assessment of the risk of contrast-induced nephropathy in children. AB - The aim of the study was to determine the usefulness of interleukin 18 (IL-18) and neutrophil-gelatinase associated lipocalin (NGAL) in the risk assessment of contrast nephropathy in children. The study included patients among whom radiological examinations were performed using intravascular contrast agent. The material consisted of 33 children (19 girls, 14 boys) aged 6.37 +/-5.41 years. 20/33 (61%) of patients had hydronephrosis, 9/33 (27%) had other urinary tract defects referred as "no hydronephrosis" and 4/33 (12%) had urolithiasis. NGAL determination was performed with the use of Human Lipocalin-2 / NGAL Immunoassay. To determine the concentration of human IL-18 an ELISA Kit (MBL International Corporation) was used. There were no statistically significant differences in the concentrations of NGAL and IL-18 in serum determined before the procedure, and after the administration of contrast agent. Concentrations of NGAL and IL-18 were determined in urine three times: before the procedure, 2-4 hours after administration of the contrast agent, and 48 hours after the performed procedure. The analysis showed that the concentration of IL-18 and NGAL in urine did not differ significantly in three consecutive preformed measurements. The study has also found no statistically significant differences between serum creatinine before and 48 hours after injection of contrast. Implementation of new biomarkers such as NGAL and IL-18 expands the possibilities of renal function assessment in children undergoing radiological procedures using contrast agents. In examined children with normal or slightly impaired renal function they did not demonstrate the risk of contrast nephropathy. PMID- 26862310 TI - Aspergillus galactomannan detection in comparison to a real-time PCR assay in serum samples from a high-risk group of patients. AB - Invasive aspergillosis (IA) is a severe infection with a 70% mortality rate. Aspergillus fumigatus is responsible for over 90% of those infections. The diagnosis of invasive aspergillosis is based on clinical sample culture and detection of fungal hyphae in histopathological examination. Additional tests may include the detection of the galactomannan antigen and of fungal genetic material in serum and bronchoalveolar washings. The present study was to assess the use of these two rapid tests in the diagnosis of invasive aspergillosis: serological one - to detect the galactomannan antigen (ELISA assay), and real-time PCR, and to establish a possible correlation between these two methods. PMID- 26862311 TI - Treatment of low doses curcumin could modulate Th17/Treg balance specifically on CD4+ T cell cultures of systemic lupus erythematosus patients. AB - INTRODUCTION: The balance between T helper 17 (Th17) and regulatory T cells (Treg) is a new paradigm in the pathogenesis of systemic lupus erythematosus (SLE). Currently, there are no drugs that able to modulate Th17/Treg balance specifically in SLE. Curcumin is a bioactive agent that has a specific action against hyperproliferative cells. However, its role in modulating Th17/Treg balance in SLE is still unknown. This research aimed to investigate the role of curcumin in modulating Th17/Treg balance on CD4+ T cell cultures of SLE patients. MATERIAL AND METHODS: CD4+ T cells from SLE 6 untreated patients and 6 healthy subjects were collected, stimulated with Th17 differentiating factors, and curcumin 0.1 and 1 ug/ml was added on cultures. After 72 hours incubation, cells were harvested and measured for Th17 and Treg percentages using flow cytometry and interleukin-17A (IL-17A) and transforming growth factor-beta1 (TGF-beta1) levels using ELISA. RESULTS: Administration of low doses of curcumin (0.1 and 1 ug/ml) could decrease Th17 percentages (p = 0.000 and p = 0.000 compared to control), reduce IL-17A productions (p = 0.000 and p = 0.000 compared to control), increase Treg percentages (p = 0.001 and p = 0.000 compared to control), and increase TGF-beta1 productions (p = 0.001 and p = 0.000 compared to control) on CD4+ T cells of SLE patients. Interestingly, these effects were not reproduced on CD4+ T cells cultures of healthy subjects. CONCLUSIONS: These data suggest that curcumin can modulate Th17/Treg balance specifically on CD4+ T cells of SLE patients without affecting healthy subjects. PMID- 26862313 TI - Venous thromboembolism and sarcoidosis: co-incidence or coexistence? AB - The association between venous thromboembolism (VTE) and sarcoidosis has been reported recently, nevertheless the true incidence of co-incident sarcoidosis and VTE is unknown. Sarcoidosis as a chronic disease of immune dysregulation might be associated with an increased risk of VTE. The mechanisms responsible for VTE development are not clear and may be influenced by several factors: activity of inflammation, clinical characteristics of sarcoidosis and comorbidities. Pulmonary embolism (PE) as a potentially fatal condition should be considered in all of the patients with sarcoidosis in whom worsening of the respiratory status is diagnosed. A high plasma D-dimers (DD) level may be suggestive of VTE, nevertheless elevated plasma DD should be interpreted with caution, in the context of the active inflammatory process. If sarcoidosis appears to be one of risk factors for VTE development, further investigations are needed to define the pro-thrombotic phenotype of this disease. PMID- 26862312 TI - The role of natural killer cells in pathogenesis of autoimmune diseases. AB - There is growing evidence that NK cell-mediated immunoregulation plays an important role in the control of autoimmunity. NK cells are a subset of lymphocytes that generally contribute to innate immunity but have also a great impact on the function of T and B lymphocytes. The major role of NK cells is cytotoxic reaction against neoplastic, infected and autoreactive cells, but they regulatory function seems to play more important role in the pathogenesis of autoimmune diseases. Numerous studies suggested the involvement of NK cells in pathogenesis of such a common autoimmune diseases as juvenile rheumatoid arthritis, type I diabetes and autoimmune thyroid diseases. The defects of NK cells regulatory function as well as cytotoxic abilities are common in patients with autoimmune diseases with serious consequences including HLH hemophagocytic lymphocytosis (HLH) and macrophage activation syndrome (MAS). The early diagnosis of NK cells defect responsible for the loss of the protective abilities is crucial for the prevention of life-threatening complications and implementation of necessary treatment. PMID- 26862314 TI - Immunological aspects of antitumor photodynamic therapy outcome. AB - Photodynamic therapy (PDT) of cancer is an efficient and promising therapeutic modality approved for the treatment of several types of tumors and non-malignant diseases. It involves administration of a non-toxic photosensitizer followed by illumination of the tumor site with a harmless visible light. A light activated photosensitizer can transfer its energy directly to molecular oxygen, leading to production of highly toxic reactive oxygen species (ROS). Antitumor effects of PDT result from the combination of three independent mechanisms involving direct cytotoxicity to tumor cells, destruction of tumor vasculature and induction of the acute local inflammatory response. PDT-mediated inflammatory reaction is accompanied by tumor infiltration of the leukocytes, enhanced production of pro inflammatory factors and cytokines. Photodynamic therapy is able to effectively stimulate both the innate and the adaptive arm of the immune system. In consequence, this regimen can lead to development of systemic and specific antitumor immune response. However, there are limited studies suggesting that under some specific circumstances, PDT on its own may exert some immunosuppressive effects leading to activation of immunosuppressive cells or cytokines production. In this report we briefly review all immunological aspects of PDT treatment. PMID- 26862315 TI - Central nervous system haemorrhage causing early death in acute promyelocytic leukaemia. AB - Acute promyelocytic leukaemia (APL) is a rare type of paediatric leukaemia characterised by a specific genetic mutation and life-threatening coagulopathy. The discovery of all-trans retinoic acid (ATRA), which acts directly on promyelocytic locus-retinoic acid receptor alpha (PML-RARalpha) gene product, brought a revolution to the therapy of this disorder. Unfortunately, despite an improvement in the complete remission rate, the early death (ED) rate has not changed significantly, and the haemorrhages remain a major problem. The most common bleeding site, which accounts for about 65-80% of haemorrhages, is the central nervous system. Second in line are pulmonary haemorrhages (32%), while gastrointestinal bleedings are relatively rare. Haemorrhages result from thrombocytopaenia, disseminated intravascular coagulopathy (DIC), and systemic fibrinolysis. Herein we present a boy aged one year and nine months with APL. The patient was not eligible for ATRA administration due to poor clinical condition. He developed bleeding diathesis that presented as disseminated intravascular coagulation (DIC) and led to intracranial haemorrhage, which resulted in the patient's death. PMID- 26862316 TI - Mycoplasma pneumoniae as a trigger for Henoch-Schonlein purpura in children. AB - Mycoplasma pneumoniae is one of the most common causes of respiratory tract infections in children. Extrapulmonary manifestations are seen in up to 25% of infected patients. Extrapulmonary complications are associated with the central nervous system, gastrointestinal tract, skin changes, myocarditis, pericarditis, hemolytic anemia, thrombocytopenia and thrombosis. The majority of extrapulmonary symptoms are associated with skin changes such as exanthematous skin eruptions, erythema nodosum, urticaria, Stevens-Jonson syndrome. M. pneumoniae stimulates production of the interleukins and tumor necrosis factor (TNF) alpha and can cause vasculitis. Henoch-Schonlein purpura (HSP) is a leucoclastic vasculitis that affects small vessels. Clinical manifestations of HSP include typical rash, arthritis, gastrointestinal and sometimes renal involvement. The main feature in HSP is abnormal IgA deposits in vessel walls. Circulating abnormal glycosylated IgA 1 and IgG antibodies form immune complexes: IgA1-IgG and anti-IgA 1. Immune complexes activate cytokines, parts of complement and influence directly the endothelium. We report cases of three children with Henoch-Schonlein purpura with prolonged and recurrent skin and joint changes. The serological analysis (positive serum IgM) confirmed Mycoplasma pneumoniae infection. Treatment with clarithromycin caused complete regression of disease. We suggest that in the case of prolonged symptoms of vasculitis due to Henoch-Schonlein purpura, Mycoplasma pneumonia infection may be a potential cause of exacerbation of the disease. PMID- 26862317 TI - DRESS syndrome associated with type 2 diabetes in a child. AB - Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is an uncommon, life-threatening drug reaction. The basic findings are skin rash, multiorgan involvement, and eosinophilia. Most of the aromatic anticonvulsants, such as phenytoin, phenobarbital and carbamazepine can induce DRESS. Herein we report a 14-year-old patient with DRESS syndrome related to carbamazepine use. The patient presented with signs of involvement of the skin, lungs, liver, and microscopic hematuria. Carbamazepine treatment was discontinued; antihistamines and steroids were started. Hyperglycemia, commencing on the first dose of the steroid given, persisted even after the discontinuation of steroids and improvement of other signs. There were no signs of pancreatitis or type 1 diabetes clinically in laboratory tests. Her blood glucose levels were regulated at first with insulin and later with metformin. Within 1 year of follow-up, still regulated with oral antidiabetics, she has been diagnosed with type 2 diabetes. Formerly, long-term sequelae related to "drug rash with eosinophilia and systemic symptoms syndrome" such as hepatic and renal failure, type 1 diabetes mellitus, Grave's disease, autoimmune hemolytic anemia, and lupus have also been reported. However, up to date, no cases with type 2 diabetes have been reported as long term sequelae. To our knowledge, this is the first case in the literature presenting with type 2 diabetes as long-term sequelae. PMID- 26862318 TI - Leukemia cell microvesicles promote survival in umbilical cord blood hematopoietic stem cells. AB - Microvesicles can transfer their contents, proteins and RNA, to target cells and thereby transform them. This may induce apoptosis or survival depending on cell origin and the target cell. In this study, we investigate the effect of leukemic cell microvesicles on umbilical cord blood hematopoietic stem cells to seek evidence of apoptosis or cell survival. Microvesicles were isolated from both healthy donor bone marrow samples and Jurkat cells by ultra-centrifugation and were added to hematopoietic stem cells sorted from umbilical cord blood samples by magnetic associated cell sorting (MACS) technique. After 7 days, cell count, cell viability, flow cytometry analysis for hematopoietic stem cell markers and qPCR for P53 gene expression were performed. The results showed higher cell number, higher cell viability rate and lower P53 gene expression in leukemia group in comparison with normal and control groups. Also, CD34 expression as the most important hematopoietic stem cell marker, did not change during the treatment and lineage differentiation was not observed. In conclusion, this study showed anti-apoptotic effect of leukemia cell derived microvesicles on umbilical cord blood hematopoietic stem cells. PMID- 26862320 TI - Genotoxic effects of boric acid and borax in zebrafish, Danio rerio using alkaline comet assay. AB - The present study is conducted to determine the potential mechanisms of Boron compounds, boric acid (BA) and borax (BX), on genotoxicity of zebrafish Danio rerio for 24, 48, 72 and 96-hours acute exposure (level:1, 4, 16, 64 mg/l BA and BX) in semi-static bioassay experiment. For that purpose, peripheral erythrocytes were drawn from caudal vein and Comet assay was applied to assess genotoxicity. Acute (96 hours) exposure and high concentrations of boric acid and borax increases % tail DNA and Olive tail moment. Genotoxicity was found for BA as concentration-dependent and BX as concentration and time dependent manner. In general, significant effects (P < 0,05) on both concentrations and exposure times were observed in experimental groups. DNA damage was highest at 96 h and 24 h for all BX and BA concentrations, respectively in peripheral blood of D. rerio. For the first time, our study demonstrates the effect of waterborne BA and BX exposure on genotoxicity at the molecular level, which may contribute to understanding the mechanism of boric acid and borax-induced genotoxicity in fish. PMID- 26862319 TI - Regulatory RNAs controlling vascular (dys)function by affecting TGF-beta family signalling. AB - Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Over the last few years, microRNAs (miRNAs) have emerged as master regulators of gene expression in cardiovascular biology and disease. miRNAs are small endogenous non-coding RNAs that usually bind to 3' untranslated region (UTR) of their target mRNAs and inhibit mRNA stability or translation of their target genes. miRNAs play a dynamic role in the pathophysiology of many CVDs through their effects on target mRNAs in vascular cells. Recently, numerous miRNAs have been implicated in the regulation of the transforming growth factor beta (TGF-beta)/bone morphogenetic protein (BMP) signalling pathway which plays crucial roles in diverse biological processes, and is involved in pathogenesis of many diseases including CVD. This review gives an overview of current literature on the role of miRNAs targeting TGF-beta/BMP signalling in vascular cells, including endothelial cells and smooth muscle cells. We also provide insight into how this miRNA-mediated regulation of TGF-beta/BMP signalling might be used to harness CVD. PMID- 26862321 TI - Classification of P-glycoprotein-interacting compounds using machine learning methods. AB - P-glycoprotein (Pgp) is a drug transporter that plays important roles in multidrug resistance and drug pharmacokinetics. The inhibition of Pgp has become a notable strategy for combating multidrug-resistant cancers and improving therapeutic outcomes. However, the polyspecific nature of Pgp, together with inconsistent results in experimental assays, renders the determination of endpoints for Pgp-interacting compounds a great challenge. In this study, the classification of a large set of 2,477 Pgp-interacting compounds (i.e., 1341 inhibitors, 913 non-inhibitors, 197 substrates and 26 non-substrates) was performed using several machine learning methods (i.e., decision tree induction, artificial neural network modelling and support vector machine) as a function of their physicochemical properties. The models provided good predictive performance, producing MCC values in the range of 0.739-1 for internal cross validation and 0.665-1 for external validation. The study provided simple and interpretable models for important properties that influence the activity of Pgp interacting compounds, which are potentially beneficial for screening and rational design of Pgp inhibitors that are of clinical importance. PMID- 26862323 TI - Highlight report: Erroneous sample annotation in a high fraction of publicly available genome-wide expression datasets. PMID- 26862322 TI - A review of environmental and occupational exposure to xylene and its health concerns. AB - Xylene is a cyclic hydrocarbon, and an environmental pollutant. It is also used in dyes, paints, polishes, medical technology and different industries as a solvent. Xylene easily vaporizes and divides by sunlight into other harmless chemicals. The aim of the present review is to collect the evidence of the xylene toxicity, related to non-cancerous health hazards, as well as to provide possible effective measurement to minimize its risk ratio. For current study a bibliographic search of more than 250 peer-reviewed papers in scientific data including PubMed, and Google Scholar about xylene was done. But approximately 130 peer-reviewed papers relevant to xylene were included (Figure 1(Fig. 1)). All scientific data was reviewed with key words of "xylene toxicity", "xylene toxic health effects", "environmental volatile organic compounds", "human exposure to xylene", "xylene poisoning in laboratory workers", "effects of xylene along with other hydrocarbons", "neurotoxicity of selected hydrocarbons", and "toxic effects of particular xylene isomers in animals". According to these studies, xylene is released into the atmosphere as fugitive emissions from petrochemical industries, fire, cigarette, from different vehicles. Short term exposure to mixed xylene or their individual isomers result in irritation of the nose, eyes and throat subsequently leading toward neurological, gastrointestinal and reproductive harmful effects. In addition long term exposure to xylene may cause hazardous effects on respiratory system, central nervous system, cardiovascular system, and renal system. The health concerns of xylene are well documented in animals and human. It is important to improve health policies, launch xylene related health and toxicity awareness campaigns, to get rid of its dangerous outcomes. Chronic diseases have become a threat to human globally, with special prominence in regions, where xylene is used with other chemicals (benzene, toluene etc.) especially in petroleum and rubber industry. The mechanism of toxicity and interactions with endocrine system should be followed up which is the main threat to human health. PMID- 26862324 TI - Transcriptomic signature for drug-induced steatosis. PMID- 26862325 TI - Interspecies extrapolation by physiologically based pharmacokinetic modeling. PMID- 26862326 TI - Highlight report: New methods for quantification of bile canalicular dynamics. PMID- 26862327 TI - Systems Toxicology. PMID- 26862329 TI - Expression classifiers for developmental toxicants. PMID- 26862328 TI - Therapy of hyperammonemia. PMID- 26862330 TI - Identification of carcinogens by a selected panel of DNA damage response associated genes. PMID- 26862331 TI - Drug-induced mitochondrial impairment in liver cells. PMID- 26862333 TI - Pharmacy practice: At the tipping point? PMID- 26862332 TI - Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats. AB - Bone marrow mesenchymal stem cells (BMMSCs) exert immunosuppressive activity in transplantation, and heme oxygenase-1 (HO-1) enhances their immunomodulatory effects. The aim of this study was to determine whether HO-1-transduced BMMSCs (HO-1/MSCs) improve rat liver transplantation (LTx) outcomes. Orthotopic LTx rejection models were treated with HO-1/MSCs, BMMSCs, HO-1, or normal saline, respectively. Our results showed a significant improvement in survival rates in the HO-1/BMMSCs group compared to the control groups. At all time points, liver function marker levels in the HO-1/MSCs group were significantly lower than in the other three groups; on POD 1, 7, and 14, the degree of rejection and apoptotic cells was significantly less in the HO-1/MSCs group than in the other three groups. Interleukin- (IL-) 10 and transforming growth factor-beta levels were significantly increased, while IL-2, IL-6, IL-17, IL-23, tumor necrosis factor-alpha, and interferon-gamma levels were significantly decreased in the HO 1/MSCs group when compared to the other groups. Splenocyte Tregs were significantly increased by HO-1/MSCs compared with controls on POD 3, 5, 7, 10, 14, and 28. Summarily, we provide evidence that HO-1/MSCs improved allogeneic LTx outcomes by attenuating inflammatory responses and acute cellular rejection, as well as enhanced immunomodulatory effects compared with BMMSCs. PMID- 26862334 TI - The "Rising Tide" of dementia in Canada: What does it mean for pharmacists and the people they care for? PMID- 26862336 TI - We know ADAPT works-Now it works for you. PMID- 26862335 TI - Multidisciplinary members' perspectives on a pharmacist joining a rheumatology practice team. AB - BACKGROUND: Pharmacist participation in chronic disease management benefits patients in many ambulatory settings. We explored the attitudes and perceptions among multidisciplinary members of a rheumatology team towards the skills and responsibilities of a pharmacist joining their practice. METHODS: The physicians, nurse, physiotherapist and staff of a rheumatology clinic were invited to participate in focus group and semistructured interviews. Practice members also completed an inventory of perceived health professional roles in the medication use process. RESULTS: Discussions with 2 physicians, a nurse, physiotherapist and 1 office administrator were conducted. Concepts related to 3 key themes included positively viewed pharmacist roles broadly related to activities that encompass provision of medication-related services for the patients, the providers and the practice. Examples of such care included educational tasks related to therapies (rheumatological and otherwise) and maintenance of accurate drug histories. These findings were reflected in high scores for perceived pharmacist roles in education and medication review responsibilities using the Medication Use Processes Matrix instrument. Most members were not comfortable with pharmacists conducting physical assessments and emphasized the need for a team member who could adapt to variations in workflow preferences across rheumatologists in the practice. INTERPRETATION: Perceived pharmacist roles expressed by existing rheumatology team members were largely consistent with the scope of pharmacist knowledge, skills and responsibilities in primary care. CONCLUSION: Overall, existing multidisciplinary staff exhibited favourable attitudes towards a pharmacist joining their practice setting. Data from this job analysis exercise were used to inform the development of a job description for a rheumatology clinical pharmacist. PMID- 26862337 TI - Pharmacy Practice Research Abstracts: Canadian Pharmacists Conference 2015. PMID- 26862338 TI - Staged inflation: An approach with achievement of optimal luminal gain and reduced rate of spontaneous coronary artery dissection. PMID- 26862339 TI - Synergistic effect of hypertension with diabetes mellitus and gender on severity of coronary atherosclerosis: Findings from Tehran Heart Center registry. AB - BACKGROUND: We performed this study to evaluate the possible synergism between hypertension and other conventional risk factors of coronary artery disease (CAD) on an angiographic severity of coronary atherosclerosis. METHODS: A cross sectional study was conducted on 10502 consecutive patients who underwent coronary angiography in the cardiac catheterization laboratory of Tehran Heart Center Hospital (Tehran University of Medical Sciences, Iran), and their conventional risk factors including male gender, hypertension, diabetes mellitus (DM), dyslipidemia, smoking, and family history of premature CAD were recorded. The severity of coronary atherosclerosis evaluated by calculation of Gensini's score. RESULTS: All aforementioned conventional risk factors of CAD were independently associated with severity of CAD. Multivariate linear regression analysis demonstrated that hypertension had synergistic effect with male gender [Excess Gensini's score: 5.93, 95% confidence interval (CI): 2.72-9.15, P < 0.001] and also with DM (Excess Gensini's score: 3.99, 95% CI: 0.30-7.69, P = 0.034) on severity of CAD. No interaction was observed between hypertension and smoking, dyslipidemia and also with a family history of CAD. CONCLUSION: Hypertension has a synergistic effect with DM and male gender on the severity of CAD. These findings imply that more effective screening and treatment strategies should be considered for early diagnosis and tight control of hypertension in male and diabetic people for prevention of advanced CAD. PMID- 26862340 TI - Dairy consumption, cardiovascular risk factors and inflammation in elderly subjects. AB - BACKGROUND: Previous epidemiological studies of dairy product consumption and health outcomes have reported mixed findings. Despite increasing in life expectancy, scarce data are available in this field in elderly individuals. We tested the hypothesis that greater dairy intake is associated with lower high sensitive C-reactive protein (hs-CRP) level and better lipid profile and glycemic control. METHODS: This cross-sectional study was undertaken on 107 elderly individuals who aged 60-78 years. Usual dietary intakes were assessed by means of a validated food frequency questionnaire (FFQ). Anthropometric measures and biochemical markers were determined using standard protocols. RESULTS: The reported mean +/- standard deviation (SD) of daily intake of dairy products and age were 588.02 +/- 418.88 g/d and 63.22 +/- 6.92 years, respectively. After control for demographic characteristics and dietary intakes, dairy consumption was not significantly related to the increased risk of insulin resistance [Odds ratio (OR): 2.19, 95% confidence interval (CI): 0.54, 8.86; P = 0.520] and elevated hs-CRP (OR: 1.54, 95% CI: 0.37, 6.35; P = 0.550). Participants in the top tertile of dairy had greater, but statistically not a significant risk of elevated triglyceride (TG), total cholesterol and low-density lipoprotein cholesterol (LDL-C). No significant relations were seen for hs-CRP, insulin resistance and lipid profile across tertiles of dairy products. CONCLUSION: In this elderly population, total dairy consumption was not associated with inflammatory biomarkers levels and other cardiometabolic risk factors. PMID- 26862342 TI - The effect of positive thinking training on the level of spiritual well-being among the patients with coronary artery diseases referred to Imam Reza specialty and subspecialty clinic in Shiraz, Iran: A randomized controlled clinical trial. AB - BACKGROUND: Positive thinking which is derived from an optimistic view toward the universe and plays an important role in the incidence of better and a more targeted behavior among human beings. It can improve spiritual health in the individuals through increased communication with God and thanksgiving and accelerate the healing process. Accordingly, we aimed to evaluate the effect of positive thinking on the level of spiritual health in the patients with coronary artery disease (CAD) referred to Imam Reza specialty and subspecialty clinic in Shiraz, Iran. METHODS: In this study randomized controlled clinical trial, we enrolled 90 patients with confirmed CAD referred to Imam Reza clinic, Shiraz, during April to July 2013. A blocking randomization method was used to randomize the final 90 participants into intervention (n = 45) and control groups (n = 45). After obtaining written informed consent, the participants were asked to complete two questionnaires. Data were collected using Ellison and Paloutzian's spiritual well-being scale (SWBS) and a demographic questionnaire. The patients in the intervention group participated in 7 training sessions on positive thinking in which several topics were discussed. The SWBS questionnaire was completed two more times by the participants; once immediately after, and once 1 month after the intervention. 16 patients were excluded from the study due to different reasons, and finally the analysis was performed on 74 patients. RESULTS: The mean +/- standard deviation (SD) of spiritual well-being (SWB) increased from 88.71 +/ 12.5 to 96.63 +/- 12.58 in the intervention group; while, it decreased from 93.19 +/- 17.55 to 94.45 +/- 16.01 in the control group in the interval of before and 1 month after the intervention. We observed a statistically significant difference between the two groups regarding both variables of time and group (P < 0.001). CONCLUSION: SWB is an important factor which should be considered in the treatment process, and nurses could maintain and improve such dimension of health in the patients through their intervention including drawing the patients' attention to optimism and positive thinking. PMID- 26862341 TI - Prognostic factors of 28 days survival rate in patients with a first acute myocardial infarction based on gender in Isfahan, Iran (2000-2009). AB - BACKGROUND: Determinant prognostic factors of 28 days survival rate in patients with a first acute myocardial infarction (AMI) based on gender in teen year's period in Isfahan, Iran, was the aim of this study. METHODS: This study is a prospective hospital-based study that consisted, all patients with AMI admitted to all hospitals (private and universal hospitals) in Isfahan and Najafabad (Iran) during 2000-2009. To determinant the prognostic factors of 28 days survival rate in patients based on gender, analysis conducted separately for male and female. In analysis, we use of t-test, log Rank tests, Kaplan-Meier method, and univariate and multivariate Cox regression model. RESULTS: Short-term (28 days) survival rate was 92.5% in male and 86.7% in female (P < 0.001). The adjusted hazard ratio (HR) of death for age group 80 years and older was 12.7 [95% confidence interval (CI): 5.14-31.3] in male and 8.78 (95% CI: 1.2-63.1) in female. HR for acute transmural MI of the unspecified site in male was 8.9 (95% CI: 4.68-16.97) and in female 9.33 (95% CI: 4.42-19.7). HR for receive of streptokinase in male was 1.11 (95% CI: 0.94-1.31) and in female was 0.69 (95% CI: 0.56-0.84). CONCLUSION: Short-term survival rate in male was a higher than female. In male age, anatomic location of MI and hospital status and in female streptokinase use and anatomic location of MI was the most important prognostic factors of survival in-patient with AMI in Isfahan. PMID- 26862343 TI - Advanced method used for hypertension's risk factors stratification: support vector machines and gravitational search algorithm. AB - BACKGROUND: The aim of this study is to present an objective method based on support vector machines (SVMs) and gravitational search algorithm (GSA) which is initially utilized for recognition the pattern among risk factors and hypertension (HTN) to stratify and analysis HTN's risk factors in an Iranian urban population. METHODS: This community-based and cross-sectional research has been designed based on the probabilistic sample of residents of Isfahan, Iran, aged 19 years or over from 2001 to 2007. One of the household members was randomly selected from different age groups. Selected individuals were invited to a predefined health center to be educated on how to collect 24-hour urine sample as well as learning about topographic parameters and blood pressure measurement. The data from both the estimated and measured blood pressure [for both systolic blood pressure (SBP) and diastolic blood pressure (DBP)] demonstrated that optimized SVMs have a highest estimation potential. RESULTS: This result was particularly more evident when SVMs performance is evaluated with regression and generalized linear modeling (GLM) as common methods. Blood pressure risk factors impact analysis shows that age has the highest impact level on SBP while it falls second on the impact level ranking on DBP. The results also showed that body mass index (BMI) falls first on the impact level ranking on DBP while have a lower impact on SBP. CONCLUSION: Our analysis suggests that salt intake could efficiently influence both DBP and SBP with greater impact level on SBP. Therefore, controlling salt intake may lead to not only control of HTN but also its prevention. PMID- 26862345 TI - Acute myocardial infarction in a young male wrestler: A case report. AB - BACKGROUND: Anabolic steroids have been widely used in recent years. It could adversely affect the cardiovascular system. Non-traditional risk factors for coronary heart diseases (CHDs) have raised great concern. CASE REPORT: A young bodybuilder was presented with crushing retrosternal chest pain, excessive diaphoresis, and vomiting. The symptoms began during wrestling. The patient did not have a history of traditional cardiovascular risk factors. He was using large quantities of nutritional and bodybuilding supplements with multiple intramuscular injections of dexamethasone during past 6 months. The electrocardiography (ECG) revealed ST-segment elevation in the precordial, I and aVL leads consistent with acute extensive myocardial infarction (MI). Lipid profile, cardiac troponin, and creatine phosphokinase-MB (CPK-MB) was abnormal. Transthoracic echocardiography (TTE) revealed mild left ventricular (LV) enlargement and reduced global systolic dysfunction with regional wall akinesia. The patient received thrombolytic therapy which was resulted in symptomatic relief and resolution in ST-T changes. Significant smoke was seen in LV cavity without clot formation on the discharge day. About 1 week later, large fresh clots were seen in the apex. He was admitted again, and the burden of clots was reduced significantly after initiation of oral warfarin. Other laboratory tests were as follows: High-sensitivity C-reactive protein (CRP): 25.9 mg/dl, homocysteine: 26.2 umol/l. The patient was discharged with specific medication. Clots were disappeared after 6 weeks of warfarin therapy. Later, the patient was evaluated again, and there was not any symptom and LV clots. CONCLUSION: Hyperhomocysteinemia could be induced by steroid abuse and may cause atherosclerotic and thrombotic effects in healthy athletes. We suggest clinicians to take a careful history of young athletes presented with MI or thrombotic events and also pay special attention to their homocysteine levels in their follow-ups. PMID- 26862344 TI - Systematic review of zinc biochemical indicators and risk of coronary heart disease. AB - BACKGROUND: Poor zinc nutritional status is suspected as a risk factor for coronary heart disease (CHD). Since zinc absorption may be influenced by some nutritional and physiologic factors, it would be better to investigate zinc status through biochemical measurements. The objective of the present study was to review recent studies investigating the association of zinc biomarkers with CHD, systematically. METHODS: The MEDLINE database was used for relevant studies published from January 2009 to December 2013 with appropriate keywords. Articles were included in this study if they were human studies, original articles, and published in English. RESULTS: Six case-control studies and two prospective cohort studies that measured zinc biomarkers were included in the study. Almost all case-control studies suggest that decreased plasma zinc was associated with increased CHD risk. Cohort studies did not support this relationship. CONCLUSION: The majority of the evidence for this theory is extracted from case-control studies, which might have bias. Prospective studies and randomized clinical trials are needed to investigate whether poor zinc status is associated with increased CHD risk. Consequently, a protective role of zinc in CHD could not be still established. PMID- 26862346 TI - Adherence to practice guidelines for coronary artery bypass graft surgery in Shiraz, Iran. AB - BACKGROUND: There is an increasing tendency to use evidence-based medicine (EBM) and guidelines among physicians. This is also true for concordance of coronary artery bypass graft (CABG) surgery and guidelines; therefore, we aimed to address the adherence to 2011 American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) guideline for CABG. METHODS: In this cross sectional study, we assessed 246 patients who underwent CABG in Shiraz, Iran, during 2011-2012, using a data collecting form provided through studying ACCF/AHA guideline 2011. The patients were categorized into clinical subgroups and then grouped into appropriate, in-appropriate and uncertain classes. Chi-square was used to compare categorical variables and t-test was used for continuous variables. RESULTS: Of the 246 patients, 70.3% were grouped into "class I," 12.6% into "class IIa," 6.9% into "class IIb" and 10.2% into "class III." Therefore, 82.9% of the patients were grouped into "appropriate," 6.9% into "uncertain," and 10.2% into group "inappropriate." CONCLUSION: We suggest that more attention is needed to be paid to these guidelines. Using these guidelines may help surgeons to have a uniform approach for patients. PMID- 26862347 TI - Neural architecture of Galathowenia oculata Zach, 1923 (Oweniidae, Annelida). AB - BACKGROUND: Oweniids are marine tubeworms burrowing in muddy sediments that in current phylogenies form an early branching lineage within Annelida. Little is known about their general morphology, in particular the nervous system. Here we provide an immunocytochemical investigation of the nervous system of Galathowenia oculata in order to discuss putative ancestral neuronal features in Oweniidae. RESULTS: Adult Galathowenia oculata have neither a supraesophageal ganglion nor ganglia associated with the ventral nerve cord. Instead, there is a dorsal brain commissure in the head collar that is engulfed by a cellular cortex. Accordingly, we herein term this neural structure "medullary brain commissure". The anterior margin of the head collar exhibits numerous neurites that emerge from the brain commissure. The dorsolateral folds are innervated by the ventrolateral neurite bundles extending from the circumesophageal connectives. In the anterior uniramous and biramous segments immunoreactive somata are distributed evenly along the ventral nerve cord and arranged metamerically in the posterior-most short segments. One dorsal and two pairs of lateral neurite bundles extend longitudinally along the body. Numerous serially arranged circular neurite bundles were labeled in anteriormost long segments. Metameric arrangement of the circular neurite bundles stained against FMRFamide and acetylated alpha-tubulin is revealed in posterior short segments. For the first time immunoreactive somata arranged in clusters are reported within the pygidium in oweniids. CONCLUSIONS: Due to the lack of head appendages and a sedentary mode of life, G. oculata exhibits a single dorsal commissure (versus a brain with four commissures in most annelids). A "medullary brain commissure" is known so far only in Oweniidae and Echiura. Lack of ganglia and metamery in the ventral nerve cord of the anteriormost segments might be the result of the elongation of these segments. In the short posterior segments the metamery of immunoreactive somata and circular neurite bundles is conserved. We hypothesize that the unpaired ventral nerve cord in adult oweniids might be a result of an initially paired ventral nerve cord that fuses during development, a condition not uncommon within Annelida. PMID- 26862348 TI - Effective alkaline metal-catalyzed oxidative delignification of hybrid poplar. AB - BACKGROUND: Strategies to improve copper-catalyzed alkaline hydrogen peroxide (Cu AHP) pretreatment of hybrid poplar were investigated. These improvements included a combination of increasing hydrolysis yields, while simultaneously decreasing process inputs through (i) more efficient utilization of H2O2 and (ii) the addition of an alkaline extraction step prior to the metal-catalyzed AHP pretreatment. We hypothesized that utilizing this improved process could substantially lower the chemical inputs needed during pretreatment. RESULTS: Hybrid poplar was pretreated utilizing a modified process in which an alkaline extraction step was incorporated prior to the Cu-AHP treatment step and H2O2 was added batch-wise over the course of 10 h. Our results revealed that the alkaline pre-extraction step improved both lignin and xylan solubilization, which ultimately led to improved glucose (86 %) and xylose (95 %) yields following enzymatic hydrolysis. An increase in the lignin solubilization was also observed with fed-batch H2O2 addition relative to batch-only addition, which again resulted in increased glucose and xylose yields (77 and 93 % versus 63 and 74 %, respectively). Importantly, combining these strategies led to significantly improved sugar yields (96 % glucose and 94 % xylose) following enzymatic hydrolysis. In addition, we found that we could substantially lower the chemical inputs (enzyme, H2O2, and catalyst), while still maintaining high product yields utilizing the improved Cu-AHP process. This pretreatment also provided a relatively pure lignin stream consisting of >=90 % Klason lignin and only 3 % xylan and 2 % ash following precipitation. Two-dimensional heteronuclear single quantum coherence (2D HSQC) NMR and size-exclusion chromatography demonstrated that the solubilized lignin was high molecular weight (Mw ~ 22,000 Da) and only slightly oxidized relative to lignin from untreated poplar. CONCLUSIONS: This study demonstrated that the fed-batch, two-stage Cu-AHP pretreatment process was effective in pretreating hybrid poplar for its conversion into fermentable sugars. Results showed sugar yields near the theoretical maximum were achieved from enzymatically hydrolyzed hybrid poplar by incorporating an alkaline extraction step prior to pretreatment and by efficiently utilizing H2O2 during the Cu-AHP process. Significantly, this study reports high sugar yields from woody biomass treated with an AHP pretreatment under mild reaction conditions. PMID- 26862349 TI - Rapid determination of chemical composition and classification of bamboo fractions using visible-near infrared spectroscopy coupled with multivariate data analysis. AB - BACKGROUND: During conversion of bamboo into biofuels and chemicals, it is necessary to efficiently predict the chemical composition and digestibility of biomass. However, traditional methods for determination of lignocellulosic biomass composition are expensive and time consuming. In this work, a novel and fast method for quantitative and qualitative analysis of chemical composition and enzymatic digestibilities of juvenile bamboo and mature bamboo fractions (bamboo green, bamboo timber, bamboo yellow, bamboo node, and bamboo branch) using visible-near infrared spectra was evaluated. RESULTS: The developed partial least squares models yielded coefficients of determination in calibration of 0.88, 0.94, and 0.96, for cellulose, xylan, and lignin of bamboo fractions in raw spectra, respectively. After visible-near infrared spectra being pretreated, the corresponding coefficients of determination in calibration yielded by the developed partial least squares models are 0.994, 0.990, and 0.996, respectively. The score plots of principal component analysis of mature bamboo, juvenile bamboo, and different fractions of mature bamboo were obviously distinguished in raw spectra. Based on partial least squares discriminant analysis, the classification accuracies of mature bamboo, juvenile bamboo, and different fractions of bamboo (bamboo green, bamboo timber, bamboo yellow, and bamboo branch) all reached 100 %. In addition, high accuracies of evaluation of the enzymatic digestibilities of bamboo fractions after pretreatment with aqueous ammonia were also observed. CONCLUSIONS: The results showed the potential of visible-near infrared spectroscopy in combination with multivariate analysis in efficiently analyzing the chemical composition and hydrolysabilities of lignocellulosic biomass, such as bamboo fractions. PMID- 26862350 TI - Comparison of adipokines in a cross-sectional study with healthy overweight, insulin-sensitive and healthy lean, insulin-resistant subjects, assisted by a family doctor primary care program. AB - BACKGROUND: In most individuals, obesity and insulin resistance coexist. However, some individuals have excessive adipose tissue mass but remain insulin sensitive. Moreover, lean individuals can develop acute inflammation-induced insulin resistance, even without excess adipose tissue mass. OBJECTIVE: Our aim was to compare inflammatory markers in overweight, insulin-sensitive and lean, insulin resistant healthy subjects. METHODS: A cross-sectional study with 1098 participants (CAMELIA project) was conducted in family doctor primary care program at Niteroi, RJ, Brazil. In the present substudy, we have selected non obese healthy subjects (n = 203). Insulin resistance was defined by a homeostatic model assessment (HOMA-IR) >2.6, and overweight subject BMIs were 25< BMI <30 kg/m2. Associations were estimated through binary logistic regression with generalized estimation equation models. RESULTS: We compared overweight, insulin sensitive healthy individuals (n = 74) with a mean age of 39.2 +/- 1.3 and lean, insulin-resistant healthy individuals (n = 18) with a mean age of 31.9 +/- 3.6. C reactive protein levels were positively correlated with body mass index in the lean, insulin-resistant group. In the multiple regression model, a positive association was observed with MCP-1 and IL-6 expression after adjustment for age, waist circumference, glycated hemoglobin, resistin, adiponectin, C-reactive protein and PAI-1 levels. CONCLUSION: Our findings suggest that a lean, insulin resistant subject may have higher pro-inflammatory marker levels (MCP-1, IL-6 and resistin) than an overweight, insulin-sensitive subject. This suggest an early risk phenotype that should further be investigated for possible prognostic implications. PMID- 26862351 TI - The contribution of transposable elements to size variations between four teleost genomes. AB - BACKGROUND: Teleosts are unique among vertebrates, with a wide range of haploid genome sizes in very close lineages, varying from less than 400 mega base pairs (Mb) for pufferfish to over 3000 Mb for salmon. The cause of the difference in genome size remains largely unexplained. RESULTS: In this study, we reveal that the differential success of transposable elements (TEs) correlates with the variation of genome size across four representative teleost species (zebrafish, medaka, stickleback, and tetraodon). The larger genomes represent a higher diversity within each clade (superfamily) and family and a greater abundance of TEs compared with the smaller genomes; zebrafish, representing the largest genome, shows the highest diversity and abundance of TEs in its genome, followed by medaka and stickleback; while the tetraodon, representing the most compact genome, displays the lowest diversity and density of TEs in its genome. Both of Class I (retrotransposons) and Class II TEs (DNA transposons) contribute to the difference of TE accumulation of teleost genomes, however, Class II TEs are the major component of the larger teleost genomes analyzed and the most important contributors to genome size variation across teleost lineages. The hAT and Tc1/Mariner superfamilies are the major DNA transposons of all four investigated teleosts. Divergence distribution revealed contrasting proliferation dynamics both between clades of retrotransposons and between species. The TEs within the larger genomes of the zebrafish and medaka represent relatively stronger activity with an extended time period during the evolution history, in contrast with the very young activity in the smaller stickleback genome, or the very low level of activity in the tetraodon genome. CONCLUSION: Overall, our data shows that teleosts represent contrasting profiles of mobilomes with a differential density, diversity and activity of TEs. The differences in TE accumulation, dominated by DNA transposons, explain the main size variations of genomes across the investigated teleost species, and the species differences in both diversity and activity of TEs contributed to the variations of TE accumulations across the four teleost species. TEs play major roles in teleost genome evolution. PMID- 26862352 TI - Applying Choosing Wisely: Antinuclear Antibody (ANA) and Sub-Serology Testing in a Safety Net Hospital System. AB - OBJECTIVE: In 2013, the American College of Rheumatology (ACR) participated in the Choosing Wisely campaign and devised a recommendation to avoid testing antinuclear antibody (ANA) subserologies without a positive ANA and clinical suspicion of disease. The goals of our study were to describe ANA and subserology ordering practices and predictors of ordering concurrent ANA and subserologies in a safety-net hospital. METHODS: We identified ANA and subserologies (dsDNA, Sm, RNP, SSA, SSB, Scl-70 and centromere) completed at Denver Health between 1/1/2005 and 12/31/2011. Variables included demographics, primary insurance, service, and setting from which the test was ordered. We performed multivariable logistic regression to determine predictors of concurrent ordering of ANA and subserologies. RESULTS: During seven years, 3221 ANA were performed in 2771 individuals and 211 (6.6%) were performed concurrently with at least one subserology. The most common concurrent subserologies were dsDNA (21.8%), SSA (20.8%), and SSB (19.7%). In the multivariable logistic analysis, significant predictors of concurrent ANA and subserologies were the labs being ordered from subspecialty care (OR 8.12, 95% CI 5.27-12.50, p-value <0.0001) or from urgent/inpatient care (OR 3.86, 95% CI 1.78-8.38, p-value 0.001). A significant predictor of decreased odds was male gender (OR 0.32, 95% CI 0.21-0.49, p-value <0.0001). Five individuals (2.2% of the negative ANA with subserologies ordered) had a negative ANA but positive subserologies. CONCLUSION: Of 3221 ANA, 6.6% were performed concurrently with subserologies, and subspecialists were more likely to order concurrent tests. A negative ANA predicted negative subserologies with rare exceptions, which validates the ACR's recommendations. PMID- 26862353 TI - Determinants of Disability in Rheumatoid Arthritis: A Community-Based Cohort Study. AB - Longitudinal care of a community-based cohort of patients with rheumatoid arthritis (RA) was evaluated retrospectively. Candidate determinants of disability included visual analog scales (VAS) for patient global assessment and pain, comorbidities, and medications. The outcome was the 'patient-acceptable symptom state' for disability as defined by the Health Assessment Questionnaire (HAQ) disability index, using a cutoff of <1.04. Two-sample t tests and multivariable logistic regression were used to determine odds ratios (OR) for associations between predictor variables and disability. Out of a total of 99 patients, 28 (28%) patients had HAQ >=1.04 at their last visit. The greatest odds of not attaining the patient-acceptable symptom state in a multivariable model was associated with corticosteroids (OR: 5.1; p=0.02), antidepressants (OR: 5.3; p=0.02), and female sex (OR: 6.5; p=0.05). In the era of biologic therapy, female sex, corticosteroids, and antidepressants remain profound determinants of disability highlighting the need to understand the underlying mechanisms. PMID- 26862354 TI - Associations of MICA Polymorphisms with Inflammatory Rheumatic Diseases. AB - Inflammatory rheumatic diseases are characterized by inflammation resulting from the immune dysregulation that usually attacks joints, skin and internal organs. Many of them are considered as complex disease that may be predisposed by multiple genes and/or genetic loci, and triggered by environmental factors such as microbiome and cellular stress. The major histocompatibility complex class I chain-related gene A (MICA) is a highly polymorphic gene that encodes protein variants expressed under cellular stress conditions, and these MICA variants play important roles in immune activation and surveillance. Recently, accumulating evidences from both genetic and functional studies have suggested that MICA polymorphisms may be associated with various rheumatic diseases, and the expression of MICA variants may attribute to the altered immune responses in the diseases. The objective of this review is to discuss potential genetic associations and pathological relevance of MICA in inflammatory rheumatic diseases that may help us to understand pathogenesis contributing to the development of these diseases. PMID- 26862356 TI - Molecular Detection of Human Cytomegalovirus (HCMV) Among Infants with Congenital Anomalies in Khartoum State, Sudan. AB - Human Cytomegalovirus (HCMV) infection still represents the most common potentially serious viral complication in humans and is a major cause of congenital anomalies in infants. This study is aimed to detect HCMV in infants with congenital anomalies. Study subjects consisted of infants born with neural tube defect, hydrocephalus and microcephaly. Fifty serum specimens (20 males, 30 females) were collected from different hospitals in Khartoum State. The sera were investigated for cytomegalovirus specific immunoglobin M (IgM) antibodies using enzyme-linked immunosorbent assay (ELISA), and for Cytomegalovirus DNA using polymerase chain reaction (PCR). Out of the 50 sera tested, one patient's (2%) sample showed HCMV IgM, but with no detectable DNA, other 4(8.2 %) sera were positive for HCMV DNA but with no detectable IgM. Various diagnostic techniques should be considered to evaluate HCMV disease and routine screening for HCMV should be introduced for pregnant women in this setting. It is vital to initiate further research work with many samples from different area to assess prevalence and characterize HCMV and evaluate its maternal health implications. PMID- 26862357 TI - Alleviating Pain in Oculoplastic Procedures by Reducing the Rate of Injection of Local Anaesthetic. AB - PURPOSE: To investigate whether the rate of infiltration of local anaesthetic influences the pain or efficacy of local anaesthesia in oculoplastic surgery. METHODS: A prospective observational study on consecutive patients undergoing a variety of oculoplastic procedures under local anaesthesia. An observer recorded the rate of injection of local anaesthetic during each procedure. The same mixture of local anaesthetic and the same needle gauge was used in all cases. Patients were asked to rate the pain of both the injection and the surgery using a visual analog scale (VAS). RESULTS: 77 consecutive patients were observed, 39/77 (50.6%) patients were female and the average age was 63.5 years (range 31 94). A statistically significant correlation was found between the rate of injection and the VAS score from the injection (p<0.0001, r=0.42). There was no significant correlation between the injection rate and the VAS score from the procedure itself (p=0.25, r=0.13). Additionally, a significant correlation was found between the injection VAS score and the procedure VAS score (p=0.0002, r=0.42). CONCLUSION: The slower the rate of injection of local anaesthetic, the less pain was reported by the patient from the injection itself. Indeed the perception of pain from the surgery overall was significantly related to the pain felt during the injection, highlighting the importance of minimising pain during the injection of the local anaesthetic. We conclude that slowing the rate of injection is an effective way of alleviating pain from administration of the anaesthetic. PMID- 26862358 TI - Non-Recurrence Complications of Fibrin Glue Use in Pterygium Surgery: Prevention and Management. AB - PURPOSE: To present complications of using fibrin glue in conjunctival-limbal autografting in pterygium surgeries other than recurrences and discuss their prevention and management strategies. MATERIALS AND METHODOLOGY: The charts of all patients who underwent fibrin glue assisted pterygium excision surgery with conjunctival-limbal autograft transplantation from 2010 to 2013 were reviewed. Patients who developed complications except recurrence postoperatively were included in this study. RESULTS: Sixteen (17.39%) of the 92 patients were detected with a complication. Graft dehiscence was diagnosed in 7 (7.6%) patients with 5 of them treated conservatively and 2 patients requiring suturing. Five (5.43%) patients were diagnosed with cyst formation between the graft and conjunctiva or in the graft-removal area; these cysts were primarily excised and no additional problems occurred. Corneal dellen developed in 3 (3.26%) patients and 2 of them regressed after cessation of topical steroids and application of lubricant therapy while one was treated with amniotic membrane transplantation. Residual fibrin glue particles had stiffened on the ocular surface, which resulted in intensive pain and irritation in one (1.08%) patient on the same day of the surgery. The patient's complaints were reduced by removing these particles from the ocular surface under topical anesthesia. CONCLUSION: Complications in fibrin glue assisted pterygium surgery are relatively different from other techniques. To avoid potential complications of fibrin glue in pterygium surgery, peroperatively ophthalmologists should ensure the conjunctival autograft and conjunctiva are properly adhered, fibrin glue remnants are completely removed from the ocular surface, and no Tenon's capsule remains between the graft and the conjunctiva. PMID- 26862359 TI - Surgical Management of Post-Traumatic Iris Cyst. AB - PURPOSE: Epithelial cysts of the iris may be primary or secondary. The management of secondary, posttraumatic iris cysts is often challenging. The purpose of this work is to report the successful surgical management of a post-traumatic iris cyst. CASE REPORT: A 38 year-old man presented with an iris cyst associated with epithelial downgrowth and total cataract, six years after sustaining a penetrating injury to his right eye. The iris cyst was excised in toto with the epithelial downgrowth, and the procedure was combined with cataract extraction and intra ocular lens implantation. The patient had good post-operative visual recovery with minimal inflammatory reaction. CONCLUSION: Post-traumatic cysts of the iris can be associated with significant ocular morbidity. Many different modalities of treatment, with varying degrees of success, have been described for the treatment of iris cysts. Excision of the iris cyst in toto is a good surgical management option, which can result in an excellent functional outcome with minimal inflammatory complications. PMID- 26862360 TI - Corneal Infection Therapy with Topical Bacteriophage Administration. AB - Staphylococcus aureus is a major pathogen in bacterial keratitis, a vision threatening disease. Although the incidence of S. aureus keratitis varies worldwide, the increasing trend of resistance to certain antibiotics makes this condition an important, global, healthcare concern. We report the case of a 65 year-old woman with nosocomial left-eye corneal abscess and interstitial keratitis.The patient then undergo topical Phage therapy with successful results. PMID- 26862355 TI - Epstein- Barr Virus: Clinical and Epidemiological Revisits and Genetic Basis of Oncogenesis. AB - Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancies. PMID- 26862362 TI - Use of water jet instruments in gastrointestinal endoscopy. AB - In recent years, water jet instruments have been used in the field of gastrointestinal endoscopy, mainly in two clinical situations: Investigation and treatment under endoscopic view. Injecting water jet into the gastrointestinal lumen is helpful for maintaining a clear endoscopic view, washing away blood or mucous in the lumen or on the surface of the tip of the endoscope. This contributes to reducing time and discomfort of examination. Water jet technology is an alternative method for dissecting soft tissue; this method does not harm the small vessels or cause mechanical or thermal damage. However, its use in clinical settings has been limited to the transmucosal injection of water into the submucosal layer that elevates the mucosa to prepare for endoscopic mucosal resection or endoscopic submucosal dissection, instead of tissue dissection, which may occur because of the continuous water jet. A preclinical study has been conducted using a pulsed water jet system as an alternative method for submucosal dissection by reducing intraoperative water consumption and maintenance of dissection capability. This review introduces recent studies pertaining to using a water jet in gastrointestinal endoscopy and discusses future prospects. PMID- 26862361 TI - Trends in Cervical Cancer Among Delivery-Related Discharges and its Impact on Maternal-Infant Birth Outcomes (United States, 1998-2009). AB - OBJECTIVES: To estimate the national prevalence of cervical cancer (CCA) in women discharged from hospital after delivery, and to examine its associations with birth outcomes. METHODS: We did a retrospective cross-sectional analysis of maternal hospital discharges in the United States (1998-2009). We used the Nationwide Inpatient Sample (NIS) database to identify hospital stays for women who gave birth. We determined length of hospital stay, in-hospital mortality, and used ICD-9-CM codes to identify CCA and all outcomes of interest. Multivariable logistic regression modeling was used to calculate adjusted odds ratios (AOR) and 95% confidence intervals (CI) for the associations between CCA and feto-maternal outcome. RESULTS: In the 12-year period from 1998 to 2009, there were 8,387 delivery hospitalizations with a CCA diagnosis, a prevalence rate of 1.8 per 100,000 (95% CI=1.6, 1.9). After adjusting for potential confounders, CCA was associated with increased odds of maternal morbidities including: anemia (AOR, 1.78, 95% CI, 1.54-2.06), anxiety (AOR, 1.95, 95% CI, 1.11-3.42), cesarean delivery (AOR, 1.67, 95% CI, 1.46-1.90), and prolonged hospital stay (AOR, 1.51, 95% CI, 1.30-1.76), and preterm birth (AOR, 1.69, 95% CI, 1.46-1.97). CONCLUSION: There is a recent increase in the prevalence of CCA during pregnancy. CCA is associated with severe feto-maternal morbidities. Interventions that promote safer sexual practice and regular screening for CCA should be promoted widely among women of reproductive age to effectively reduce the prevalence of CCA during pregnancy and its impact on the health of mother and baby. PMID- 26862364 TI - Biliary and pancreatic stenting: Devices and insertion techniques in therapeutic endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography. AB - Stents are tubular devices made of plastic or metal. Endoscopic stenting is the most common treatment for obstruction of the common bile duct or of the main pancreatic duct, but also employed for the treatment of bilio-pancreatic leakages, for preventing post- endoscopic retrograde cholangiopancreatography pancreatitis and to drain the gallbladder and pancreatic fluid collections. Recent progresses in techniques of stent insertion and metal stent design are represented by new, fully-covered lumen apposing metal stents. These stents are specifically designed for transmural drainage, with a saddle-shape design and bilateral flanges, to provide lumen-to-lumen anchoring, reducing the risk of migration and leakage. This review is an update of the technique of stent insertion and metal stent deployment, of the most recent data available on stent types and characteristics and the new applications for biliopancreatic stents. PMID- 26862365 TI - Review of current and evolving clinical indications for endoscopic ultrasound. AB - For the first several years after its development, endoscopic ultrasound (EUS) was primarily limited to identification of pancreatic malignancies. Since this time, the field of EUS has advanced at a tremendous speed in terms of additional clinical diagnostic and therapeutic uses. The combination of ultrasound with endoscopy provides a unique interventional modality that is a minimally invasive alternative to various surgical interventions. Given the expanding recommended indications for EUS, this article will serve to review the most common uses with supporting evidence, while also exploring innovative endeavors that may soon become common clinical practice. PMID- 26862363 TI - Diagnostic and therapeutic biomarkers in pancreaticobiliary malignancy. AB - Pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) are two malignancies that carry significant morbidity and mortality. The poor prognoses of these cancers are strongly related to lack of effective screening modalities as well as few therapeutic options. In this review, we highlight novel biomarkers that have the potential to be used as diagnostic, prognostic and predictive markers. The focus of this review is biomarkers that can be evaluated on endoscopically-obtained biopsies or brush specimens in the pre-operative setting. We also provide an overview of novel serum based markers in the early diagnosis of both PDAC and CCA. In pancreatic cancer, the emphasis is placed on prognostic and theranostic markers, whereas in CCA the utility of molecular markers in diagnosis and prognosis are highlighted. PMID- 26862367 TI - Second-look endoscopy and factors associated with delayed bleeding after endoscopic submucosal dissection. AB - Endoscopic submucosal dissection (ESD) is a widely used procedure as curative treatment for superficial gastric neoplasms, including early gastric cancer without lymph node metastasis. However, ESD requires advanced endoscopic skill and there is a major concern regarding complications from bleeding. So far, extensive efforts have been made to develop strategies to reduce post-ESD bleeding. Use of proton pump inhibitors and coagulating exposed vessels on the ulcer floor after ESD are strategies known to reduce the risk of delayed bleeding. Second-look endoscopy (SLE) is also carried out to reduce delayed bleeding following ESD in many institutions. However, the incidence of bleeding still remains around 5%, and further measures are needed to reduce delayed bleeding after gastric ESD. Recently, three randomized studies indicated that routine SLE was unnecessary. Although routine SLE may not be recommended for all patients after gastric ESD, SLE might be an important tool for the prevention of the delayed bleeding in selected high-risk patients. Thus, the identification of the risk factors, such as large size of resected specimen and treatment with multiple antiplatelet medications, may help to further guide clinicians in deciding whether to perform SLE. Studies carried out on larger cohorts are necessary to clarify the efficacy of SLE after ESD in the prevention of post-ESD bleeding in potentially high-risk patients. PMID- 26862368 TI - Safety of immediate endoscopic sphincterotomy in acute suppurative cholangitis caused by choledocholithiasis. AB - AIM: To examine the safety of immediate endoscopic sphincterotomy (EST) in patients with acute suppurative cholangitis (ASC) caused by choledocholithiasis, as compared with elective EST. METHODS: Patients with ASC due to choledocholithiasis were allocated to two groups: Those who underwent EST immediately and those who underwent EBD followed by EST 1 wk later because they were under anticoagulant therapy, had a coagulopathy (international normalized ratio > 1.3, partial thromboplastin time greater than twice that of control), or had a platelet count < 50000 * 10(3)/MUL. One of four trainees [200-400 cases of endoscopic retrograde cholangiopancreatography (ERCP)] supervised by a specialist (> 10000 cases of ERCP) performed the procedures. The success and complication rates associated with EST in each group were examined. RESULTS: Of the 87 patients with ASC, 59 were in the immediate EST group and 28 in the elective EST group. EST was successful in all patients in both groups. There were no complications associated with EST in either group of patients, although white blood cell count, C-reactive protein, total bilirubin, and serum concentrations of liver enzymes just before EST were significantly higher in the immediate EST group than in the elective EST group. CONCLUSION: Immediate EST can be as safe as elective EST for patients with ASC associated with choledocholithiasis provided they are not under anticoagulant therapy, or do not have a coagulopathy or a platelet count < 50000 * 10(3)/MUL. Moreover, the procedure was safely performed by a trainee under the supervision of an experienced specialist. PMID- 26862366 TI - Treatment of gastric outlet obstruction that results from unresectable gastric cancer: Current evidence. AB - Malignant gastric outlet obstruction (GOO) is a common condition that results from locally advanced malignancies in the upper gastrointestinal tract, such as pancreatic, gastric, and other carcinomas. Two types of procedures for malignant GOO, namely, gastrojejunostomy (GJ) with laparotomy or a laparoscopic approach and endoscopic stenting (ES), are currently available. Although numerous previous reports have clarified the benefits and drawbacks of each procedure, whether GJ or ES should be used in patients with GOO that results from gastric cancer who may have a longer life expectancy than patients with other malignancies has not been determined. In this review, which focuses on gastric cancer-induced GOO, we analyzed the two systematic reviews and a meta-analysis that compared GJ and ES and outlined the current status of GOO treatment. We also provide an updated review that includes laparoscopic GJ. Various data from 13 studies in one review and 6 studies in another review were analyzed. Although the main results of the present review indicated that both GJ and ES were efficacious treatments in patients with GOO that resulted from gastric cancer, current evidence suggests that GJ may be the preferable procedure given its good performance status and improved prognosis in gastric cancer patients. PMID- 26862369 TI - Percutaneous endoscopic gastrostomy under steady pressure automatically controlled endoscopy: First clinical series. AB - AIM: To elucidate the safety of percutaneous endoscopic gastrostomy (PEG) under steady pressure automatically controlled endoscopy (SPACE) using carbon dioxide (CO2). METHODS: Nine patients underwent PEG with a modified introducer method under conscious sedation. A T-tube was attached to the channel of an endoscope connected to an automatic surgical insufflator. The stomach was inflated under the SPACE system. The intragastric pressure was kept between 4-8 mmHg with a flow of CO2 at 35 L/min. Median procedure time, intragastric pressure, median systolic blood pressure, partial pressure of CO2, abdominal girth before and immediately after PEG, and free gas and small intestinal gas on abdominal X-ray before and after PEG were recorded. RESULTS: PEG was completed under stable pneumostomach in all patients, with a median procedural time of 22 min. Median intragastric pressure was 6.9 mmHg and median arterial CO2 pressure before and after PEG was 42.1 and 45.5 Torr (NS). The median abdominal girth before and after PEG was 68.1 and 69.6 cm (NS). A mild free gas image after PEG was observed in two patients, and faint abdominal gas in the downstream bowel was documented in two patients. CONCLUSION: SPACE might enable standardized pneumostomach and modified introducer procedure of PEG. PMID- 26862370 TI - Endoscopic ultrasound-guided ethanol ablation of pancreatic neuroendocrine tumours: A case study and literature review. AB - Here we offer a review of the literature regarding endoscopic ultrasound-guided ethanol ablation for pancreatic neuroendocrine tumours and describe the case of a cystic tumour completely ablated after a multisession procedure. A total of 35 PubMed indexed cases of treated functioning and non-functioning pancreatic neuroendocrine tumours resulted from our search, 29 of which are well-documented and summarised. Endoscopic ultrasound-guided ethanol ablation appears as a local, minimally invasive treatment of pancreatic neuroendocrine tumours, suitable for selected patients. This technique appears feasible, relatively safe and efficient, especially when applied to symptom relief in functioning tumours, aiming at loss of endocrine secretion. For non-functioning tumours, where the goal is complete tissue ablation, eus guided ethanol ablation can provide good results for patients who are unfit for surgery or for those who refuse surgical resection. Its role in "fit for surgery" patients requires assessment through further studies. PMID- 26862371 TI - Diabetes in migrants and ethnic minorities in a changing World. AB - On a worldwide scale, the total number of migrants exceeds 200 million and is not expected to reduce, fuelled by the economic crisis, terrorism and wars, generating increasing clinical and administrative problems to National Health Systems. Chronic non-communicable diseases (NCD), and specifically diabetes, are on the front-line, due to the high number of cases at risk, duration and cost of diseases, and availability of effective measures of prevention and treatment. We reviewed the documents of International Agencies on migration and performed a PubMed search of existing literature, focusing on the differences in the prevalence of diabetes between migrants and native people, the prevalence of NCD in migrants vs rates in the countries of origin, diabetes convergence, risk of diabetes progression and standard of care in migrants. Even in universalistic healthcare systems, differences in socioeconomic status and barriers generated by the present culture of biomedicine make high-risk ethnic minorities under-treated and not protected against inequalities. Underutilization of drugs and primary care services in specific ethnic groups are far from being money-saving, and might produce higher hospitalization rates due to disease progression and complications. Efforts should be made to favor screening and treatment programs, to adapt education programs to specific cultures, and to develop community partnerships. PMID- 26862372 TI - Role of diabetes in heart rhythm disorders. AB - The incidence of diabetes mellitus (DM) is increasing rapidly. DM is the leading cause of cardiovascular diseases, which can lead to varied cardiovascular complications by aggravated atherosclerosis in large arteries and coronary atherosclerosis, thereby grows the risk for macro and microangiopathy such as myocardial infarction, stroke, limb loss and retinopathy. Moreover diabetes is one of the strongest and independent risk factor for cardiovascular morbidity and mortality, which is associated frequently with rhythm disorders such as atrial fibrillation (AF) and ventricular arrhythmias (VA). The present article provides a concise overview of the association between DM and rhythm disorders such as AF and VA with underlying pathophysiological mechanisms. PMID- 26862373 TI - Prediction of anticancer peptides against MCF-7 breast cancer cells from the peptidomes of Achatina fulica mucus fractions. AB - Several reports have shown antimicrobial and anticancer activities of mucous glycoproteins extracted from the giant African snail Achatina fulica. Anticancer properties of the snail mucous peptides remain incompletely revealed. The aim of this study was to predict anticancer peptides from A. fulica mucus. Two of HPLC separated mucous fractions (F2 and F5) showed in vitro cytotoxicity against the breast cancer cell line (MCF-7) and normal epithelium cell line (Vero). According to the mass spectrometric analysis, 404 and 424 peptides from the F2 and F5 fractions were identified. Our comprehensive bioinformatics workflow predicted 16 putative cationic and amphipathic anticancer peptides with diverse structures from these two peptidome data. These peptides would be promising molecules for new anti-breast cancer drug development. PMID- 26862375 TI - Methicillin-Resistant Staphylococcus aureus Isolated From Various Types of Hospital Infections in Pediatrics: Panton-Valentine Leukocidin, Staphylococcal Chromosomal Cassette mec SCCmec Phenotypes and Antibiotic Resistance Properties. AB - BACKGROUND: Staphylococcus aureus has long been considered as a major pathogen of hospital infections. OBJECTIVES: The present investigation was carried out to study the distribution of Staphylococcal Chromosomal Cassette mec (SCCmec) types, Panton-Valentine Leukocidin (PVL) gene and antibiotic resistance properties of Methicillin Resistant Staphylococcus aureus (MRSA) strains isolated from various types of infections found in Iranian pediatric patients. PATIENTS AND METHODS: Two-hundred and fifty-five clinical specimens were collected from four major provinces of Iran. Samples were cultured and the MRSA strains were subjected to Polymerase Chain Reaction (PCR). The patterns of antibiotic resistance were determined using the disk diffusion method. RESULTS: Seventy-four out of 255 (29.01%) clinical samples were positive for MRSA. Of the 74 MRSA strains, 47 (63.51%) were PVL positive. The clinical samples of respiratory tract infections (36.36%), those from the Shiraz province (37.87%) and samples collected during the summer season (56.48%) were the most commonly infected samples. The most commonly detected antibiotic resistance genes were tetK (89.18%), mecA (71.62%), msrA (56.75%) and tetM (54.05%). Methicillin Resistant Staphylococcus aureus had the highest levels of resistance against penicillin (100%), tetracycline (98.64%), ampicillin (93.24%) and oxacillin (93.24%). The most commonly detected SCCmec types in the MRSA strains were type V (18.91%) and III (17.56%). CONCLUSIONS: Regular surveillance of hospital-associated infections and monitoring of the antibiotic sensitivity patterns are required to reduce the prevalence of MRSA. We recommend initial management of children affected by MRSA with imipenem, lincomycin and cephalothin prescriptions. PMID- 26862374 TI - Self-assembling protein nanoparticles in the design of vaccines. AB - For over 100 years, vaccines have been one of the most effective medical interventions for reducing infectious disease, and are estimated to save millions of lives globally each year. Nevertheless, many diseases are not yet preventable by vaccination. This large unmet medical need demands further research and the development of novel vaccines with high efficacy and safety. Compared to the 19th and early 20th century vaccines that were made of killed, inactivated, or live attenuated pathogens, modern vaccines containing isolated, highly purified antigenic protein subunits are safer but tend to induce lower levels of protective immunity. One strategy to overcome the latter is to design antigen nanoparticles: assemblies of polypeptides that present multiple copies of subunit antigens in well-ordered arrays with defined orientations that can potentially mimic the repetitiveness, geometry, size, and shape of the natural host-pathogen surface interactions. Such nanoparticles offer a collective strength of multiple binding sites (avidity) and can provide improved antigen stability and immunogenicity. Several exciting advances have emerged lately, including preclinical evidence that this strategy may be applicable for the development of innovative new vaccines, for example, protecting against influenza, human immunodeficiency virus, and respiratory syncytial virus. Here, we provide a concise review of a critical selection of data that demonstrate the potential of this field. In addition, we highlight how the use of self-assembling protein nanoparticles can be effectively combined with the emerging discipline of structural vaccinology for maximum impact in the rational design of vaccine antigens. PMID- 26862376 TI - Comparison of Biological and Immunological Characterization of Lipopolysaccharides From Brucella abortus RB51 and S19. AB - BACKGROUND: Brucella abortus RB51 is a rough stable mutant strain, which has been widely used as a live vaccine for prevention of brucellosis in cattle instead of B. abortus strain S19. B. abortus lipopolysaccharide (LPS) has unique properties in comparison to other bacterial LPS. OBJECTIVES: In the current study, two types of LPS, smooth (S-LPS) and rough (R-LPS) were purified from B. abortus S19 and RB51, respectively. The aim of this study was to evaluate biological and immunological properties of purified LPS as an immunogenical determinant. MATERIALS AND METHODS: Primarily, S19 and RB51 LPS were extracted and purified by two different modifications of the phenol water method. The final purity of LPS was determined by chemical analysis (2-keto-3-deoxyoctonate (KDO), glycan, phosphate and protein content) and different staining methods, following sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). C57BL/6 mice were immunized subcutaneously three times at biweekly intervals with the same amount of purified LPSs. The humoral immunity was evaluated by measuring specific IgG levels and also different cytokine levels, such as IFN-gamma, TNF-alpha, IL-4 and IL-10, were determined for assessing T-cell immune response. RESULTS: Biochemical analysis data and SDS-PAGE profile showed that the chemical nature of S19 LPS is different from RB51 LPS. Both S and R-LPS induce an immune response. T-cell immune response induced by both S and R-LPS had almost the same pattern whereas S19 LPS elicited humoral immunity, which was higher than RB51 LPS. CONCLUSIONS: Purified LPS can be considered as a safe adjuvant and can be used as a component in prophylactic and therapeutic vaccines targeting infectious disease, cancer and allergies. PMID- 26862377 TI - Torque Teno Midi Virus/Small Anellovirus in Sera of Healthy, HIV/HCV and HIV Infected Individuals in Lorestan Province, Iran. AB - BACKGROUND: Torque Teno Midi Virus/Small Anellovirus (TTMDV/SAV) is a member of the Gammatorquevirus genus within the family Anelloviridae. It is detected in healthy, Hepatitis B Virus, Hepatitis C Virus and HIV infected individuals and also patients with acute respiratory disease in different countries, but its role in clinical diseases and its full geographical distribution is still unclear. OBJECTIVES: The current study aimed to detect the frequency of infection with TTMDV/SAV in the sera of healthy blood donors, hepatitis C infected and HIV positive individuals in Lorestan province, Iran; and also investigate the possible role of TTMDV/SAV virus in liver diseases. MATERIALS AND METHODS: Fifty two, 36, 4, and 110 serum samples from HIV positive, patients with HIV/HCV and HIV/HCV/HBV co-infections, and healthy individuals were collected in Khorramabad city, respectively. Nested-polymerase chain reaction was performed using SMAs/SMAr primers to detect TTMDV/SAV DNA. Serum aminotransferases were measured. RESULTS: In the HIV/HCV, HIV/HCV/HBV, HIV, and control cases, 29 (80.5%), 3 (75%), 43 (82.7%), and 16 (14.5%) were positive for DNA of TTMDV/SAV, respectively. In the HIV/HCV infected cases and HIV positive cases the level of Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were not significantly different in TTMDV/SAV infected and non-infected individuals (P > 0.05). CONCLUSIONS: Although significant differences (P < 0.01) were observed in the frequency of TTMDV/SAV between healthy controls and each of the HIV positive and HIV/HCV co-infected individuals, no significant difference was observed between HIV positive and HIV/HCV co-infected cases, which may be due to HIV associated immunodeficiency. This is the first time that TTMDV/SAV is reported in HIV infected individuals worldwide. Interpretation of the high frequency of the virus (82.7%) in HIV cases needs more detailed studies. PMID- 26862378 TI - High Frequency of vacA s1m2 Genotypes Among Helicobacter pylori Isolates From Patients With Gastroduodenal Disorders in Kermanshah, Iran. AB - BACKGROUND: Helicobacter pylori infection and related diseases outcome are mediated by a complex interplay between bacterial, host and environmental factors. Several distinct virulence factors of H. pylori have been shown to be associated with different clinical outcomes. Here we focused on vacA and cagA genotypes of H. pylori strains isolated from patients with gastric disorder. OBJECTIVES: The aim of this study was to determine the frequency of two toxins and genotypes of VacA toxin in patients referred to a central hospital in the west of Iran (Imam Reza hospital, Kermanshah) during 2011 - 2012. PATIENTS AND METHODS: Samples were collected from patients infected with H. pylori. Gastric biopsy specimens from the stomach antrum and corpus were cultured. PCR analysis was performed for genotyping H. pylori vacA and cagA genes. RESULTS: Helicobacter pylori was isolated from 48% (96/200) of patients with gastroduodenal disorders. In 81/96 (84%) cases, the cagA gene was present. Among different genotypes of vacA, two s1m2 and s2m2 genotypes were dominant with frequency of 39.5% and 50%, respectively. The frequency of the s1m1 genotype was 7.2% (7/96), which is much lower than elsewhere. H. pylori isolates with positive results for cagA gene and vacA s1m2 genotypes showed statistically significant correlation with peptic ulcer (s1m2 13/34 [38.2%] P = 0.003). However, isolates of H. pylori infection with cagA gene and vacA s2m2 genotypes were significantly associated with development of gastritis (s2m2 41/42 [97.6%] P = 0.000). CONCLUSIONS: About 90% of H. pylori strains potentially contained vacA s2m2 and s1m2 genotypes. Infection with H. pylori strain containing the cagA gene or the vacA s1m1 and s1m2 genotypes was associated with increased incidence of peptic ulcer disease (PUD). PMID- 26862379 TI - Crimean-Congo Hemorrhagic Fever Virus Gn Bioinformatic Analysis and Construction of a Recombinant Bacmid in Order to Express Gn by Baculovirus Expression System. AB - BACKGROUND: Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the nairovirus, a genus in the Bunyaviridae family, which causes a life threatening disease in human. Currently, there is no vaccine against CCHFV and detailed structural analysis of CCHFV proteins remains undefined. The CCHFV M RNA segment encodes two viral surface glycoproteins known as Gn and Gc. Viral glycoproteins can be considered as key targets for vaccine development. OBJECTIVES: The current study aimed to investigate structural bioinformatics of CCHFV Gn protein and design a construct to make a recombinant bacmid to express by baculovirus system. MATERIALS AND METHODS: To express the Gn protein in insect cells that can be used as antigen in animal model vaccine studies. Bioinformatic analysis of CCHFV Gn protein was performed and designed a construct and cloned into pFastBacHTb vector and a recombinant Gn-bacmid was generated by Bac to Bac system. RESULTS: Primary, secondary, and 3D structure of CCHFV Gn were obtained and PCR reaction with M13 forward and reverse primers confirmed the generation of recombinant bacmid DNA harboring Gn coding region under polyhedron promoter. CONCLUSIONS: Characterization of the detailed structure of CCHFV Gn by bioinformatics software provides the basis for development of new experiments and construction of a recombinant bacmid harboring CCHFV Gn, which is valuable for designing a recombinant vaccine against deadly pathogens like CCHFV. PMID- 26862380 TI - Medicinal Plants for the Treatment of Acne Vulgaris: A Review of Recent Evidences. AB - CONTEXT: Acne vulgaris affects about 85% of teenagers and may continue to adulthood. There are about two million visits to physicians per year for teenagers and the direct cost of acne treatment in the US exceeds $1 billion per year. EVIDENCE ACQUISITION: A wide variety of treatment regimens exist for acne vulgaris including benzoil peroxide, retinoids, isotretinoids, keratolytic soaps, alpha hydroxy acids, azelaic acid, salicilic acid as well as hormonal, anti androgen or antiseborrheic treatments. However, none of these methods is free of side effects and their exact role in therapy is not clear. In this paper apart from presenting the possible causes of acne vulgaris and its available drugs, recently published papers about medicinal plants used in the treatment of acne vulgaris were reviewed. RESULTS: Consumption of alternative and complementary medicine, including medicinal plants, is increasing and is common amongst patients affected by acne and infectious skin diseases. Medicinal plants have a long history of use and have been shown to possess low side effects. These plants are a reliable source for preparation of new drugs. CONCLUSIONS: Many plants seem to have inhibitory effects on the growth of bacteria, fungi and viruses in vitro. However, there are a few clinical evidences about the effectiveness and safety of these plants in the treatment of acne and other skin infections. PMID- 26862381 TI - Post-Vaccination Disseminated Bacillus Calmette Guerin Infection Among Children in Southern Iran. AB - BACKGROUND: Disseminated bacillus calmette guerin (BCG) infection is a rare but life threatening complication of BCG vaccination. It has been mainly seen in severe immune deficiency. A precise and rapid diagnosis is crucial for prompt initiation of an aggressive anti-mycobacterial treatment. Polymerase chain reaction (PCR) is directly applicable to smear-positive clinical specimens, proven to be a rapid and specific diagnostic test. OBJECTIVES: The aim of this study was to investigate disseminated BCG infection among 34 children in southern Iran, mainly confirmed by PCR. PATIENTS AND METHODS: We included all the patients hospitalized with disseminated BCG infection at a referral teaching hospital in southern Iran between years 1990 and 2007. The clinical and laboratory data including the immunological workups were obtained through a review of the medical files. We recalled all pathology samples from pathology specimen banks and used an in-house PCR specific for Mycobacterium bovis BCG substrain to confirm the diagnosis. RESULTS: From the total of 34 children hospitalized with disseminated BCG infection, 21 were categorized as definite and 13 probable. Thirty-one patients (91%) were under two years of age and 41% were male. The most common clinical findings were fever in 31 (91.2%), axillary's lymphadenopathy in 26 (76.5%), hepatosplenomegaly in 25 (73.5%), stunted growth in 21 (61.8%), and distant lymphadenopathy in 16 (47.1%). Polymerase Chain Reaction positivity rate was 100% (9 of 9) in bone marrow smear slides and 84.2% (16 of 19) for formalin fixed and paraffin-embedded tissue specimens. Immunodeficiency state was detected in 50% and the overall mortality rate was 58.8% (20 of 34). CONCLUSIONS: Disseminated BCG infection should be considered in the differential diagnosis of infants and young children with fever, hepatosplenomegaly, lymphadenopathy, and history of BCG vaccination. The PCR method has a high positivity rate and can serve as a useful tool for the rapid and specific identification of M. bovis BCG substrain infection. PMID- 26862383 TI - Bactericidal and Antibiotic Synergistic Effect of Nanosilver Against Methicillin Resistant Staphylococcus aureus. AB - BACKGROUND: Methicillin-Resistant Staphylococcus aureus (MRSA) are bacteria responsible for several difficult-to-treat infections in humans. These strains have developed, through the process of natural selection. Infections by MRSA are more difficult to treat with standard types of antibiotics and thus more dangerous to human health. OBJECTIVES: The aim of this study was to evaluate the bactericidal and antibiotic synergistic effect of silver nanoparticles (Ag-NPs) against MRSA. MATERIALS AND METHODS: Methicillin-Resistant Staphylococcus aureus strains were isolated from clinical samples and identified, and their susceptibility was tested using the MicroScan(r) WalkAway-96(r) SI System. minimum inhibitory concentration (MIC) was determined by a microdilution method. Time kill assay was performed by exposing the MRSA isolates to different concentrations of Ag-NPs and monitoring bacterial growth, by measuring optical density at 600 nm. Tissue culture plate was used for determination of the efficacy of Ag-NPs and their combination with antibiotics in the elimination of formed biofilm. RESULTS: The MIC value of Ag-NPs against MRSA was 100 MUg/mL. Methicillin-Resistant Staphylococcus aureus cells were treated with 50, 100 and 200 ug/mL of Ag-NPs and inhibited bacterial growth so that after four hours, almost all treated MRSA cells were dead. All combinations showed effectiveness against MRSA. It was observed that MRSA did not show inhibition zones with ampicillin alone. CONCLUSIONS: Silver Nanoparticles have high therapeutic activity against MRSA, thus can be suggested as an alternative or adjuvant with antibiotics for MRSA treatment. Further studies are required to understand the synergistic effect of Ag-NPs combinations and to assess the safety and efficacy of new antibiotic-Ag-NPs combinations. PMID- 26862382 TI - Study of the Association of Mutant HBsAg Gene and Hodgkin and Non-Hodgkin Lymphoma. AB - BACKGROUND: Hepatitis B Virus (HBV) is responsible for chronic, acute, and fulminant hepatitis, which are prevalent worldwide. Chronic HBV may lead to cirrhosis and hepatocellular carcinoma. Several epidemiological studies have indicated that hepatitis B virus is involved in B-cell Hodgkin and Non-Hodgkin Lymphoma (NHL). OBJECTIVES: The aim of this study was to evaluate the association between hepatitis B infection and Hodgkin and non-Hodgkin Lymphoma. MATERIALS AND METHODS: Paraffin embedded of 41 block samples including 12 (29.26%) Hodgkin and 29 (70.73%) non-Hodgkin patients were collected. Next, DNA extraction was carried out for all the samples followed by HBV DNA detection by the nested polymerase chain reaction (PCR). The positive HBV DNA samples were sequenced, and HBV genotypes and HBV subtypes were determined. RESULTS: Three out of 12 (25%) Hodgkin samples and seven out of 29 (24.13%) non-Hodgkin showed positive HBV DNA results. The results of sequencing revealed that the D genotype was predominant among the positive HBV patients. Interestingly an unpredictable amino acid proline was detected in position 88 of the HBs gene, which indicates a new mutation in the "S" region of HBV DNA in patients with Hodgkin and non-Hodgkin lymphoma. CONCLUSIONS: A high rate of 25% and 24.13% of HBV DNA was detected among patients with Hodgkin and non-Hodgkin lymphoma, respectively. PMID- 26862384 TI - High Frequency of Human Papillomavirus Genotype 16 Among Patients With Anogenital Warts. AB - BACKGROUND: Human Papillomavirus (HPV) infection is considered the most prevalent sexually transmitted virus infection. Human Papillomavirus 16 and 18 have been documented as high-risk HPV infections and responsible for 70% of all cervical cancers. OBJECTIVES: The aim of this study was to determine HPV genotypes in patients with anogenital warts. PATIENTS AND METHODS: In this study lesion samples were collected from 54 patients with an age ranged of 19 to 44 years. Initially, DNA extraction was carried out for all samples followed by detection of HPV DNA by the polymerase chain reaction. The positive PCR products were sequenced and the results were blasted to determine HPV genotypes. RESULTS: Out of 54 samples, 46 (85.18%) cases showed positive results for HPV DNA. A total of 26 (56.6%) samples were males and 20 (43.4%) females while eight (14.81%) showed HPV negative results. Overall, 37 (80%) patients had multiple sexual partners, and nine (20%) had one sexual partner. The frequency of anogenital warts was higher in married patients. The results of sequencing revealed that frequency of HPV16, HPV11 and HPV6 was 58.69%, 26.08% and 15.21%, respectively. CONCLUSIONS: Human Papillomavirus 16 as a high risk HPV was found to have the highest frequency among patients with anogenital warts. PMID- 26862385 TI - Expression of NS3/NS4A Proteins of Hepatitis C Virus in Huh7 Cells Following Engineering Its Eukaryotic Expression Vector. AB - BACKGROUND: Although the development of novel therapeutic regimens to combat hepatitis C virus (HCV) infection have been speeded up with successful results, no efficient vaccines exist yet. OBJECTIVES: This study aimed to construct a eukaryotic expression vector encoding nonstructural proteins, NS3/NS4A, of HCV genotype 3a, and evaluate its expression on Huh7 cell surface. MATERIALS AND METHODS: The NS3/NS4A sequence was isolated from a patient with HCV-3a chronic infection, cloned into intermediate vector pTZ57R/T, and then used for engineering a mammalian expression vector, pDisplay, to direct the respective protein to the secretory pathway and anchor it to the plasma membrane. The expression of the protein in Huh7 cell, which was transiently transfected with the vector using Lipofectamine, was determined by immunocytochemical staining assay with fluorescein isothiocyanate (FITC)-conjugated antibodies to the HA/myc tags located besides the fusion fragment. RESULTS: The results showed that the fragment was successfully amplified and cloned into a eukaryotic expression vector. Sequencing and enzyme digestion analysis confirmed the cloned gene completion and its correct position in the pDisply-NS3/NS4A plasmid. Immunocytochemical staining revealed that the target protein was expressed as a membrane-anchored protein in the Huh7 cells. CONCLUSIONS: This study can serve as a fundamental experiment for the construction of a NS3/NS4A eukaryotic expression vector and its expression in mammalian cells. Further research is underway to evaluate the fragment immunogenicity in lab animal models. PMID- 26862387 TI - Production of IFN-gamma and IL-4 Against Intact Catalase and Constructed Catalase Epitopes of Helicobacter pylori From T-Cells. AB - BACKGROUND: Helicobacter pylori infection is highly prevalent in the developing countries. It causes gastritis, peptic ulcer disease, and gastrocarcinoma. Treatment with drugs and antibiotics is problematic due to the following reasons: cost, resistance to antibiotics, prolonged treatment and using multiple drugs. Catalase is highly conserved among the Helicobacter species and is important to the survival of the organism. It is expressed in high amounts and is exposed to the surface of this bacterium; therefore it represents a suitable candidate vaccine antigen. OBJECTIVES: A suitable approach in H. pylori vaccinology is the administration of epitope based vaccines. Therefore the responses of T-cells (IFN gamma and IL-4 production) against the catalase of H. pylori were determined. Then the quality of the immune responses against intact catalase and three epitopes of catalase were compared. MATERIALS AND METHODS: In this study, a composition of three epitopes of the H. pylori catalase was selected based on Propred software. The effect of catalase epitopes on T-cells were assayed and immune responses identified. RESULTS: The results of IFN-gamma, IL-4 production against antigens, epitopes, and recombinant catalase by T-cells were compared for better understanding of epitope efficiency. CONCLUSIONS: The current research demonstrated that epitope sequence stimulates cellular immune responses effectively. In addition, increased safety and potency as well as a reduction in time and cost were advantages of this method. Authors are going to use this sequence as a suitable vaccine candidate for further research on animal models and humans in future. PMID- 26862386 TI - The Prevalence and Genotype Distribution of Human Papillomavirus in the Genital Tract of Males in Iran. AB - BACKGROUND: Human papillomavirus (HPV) is the most common viral sexually transmitted infection. Despite HPV infection is associated with several malignant disorders including penile and anal cancers, little is known about the epidemiology of HPV infection in males, particularly in developing countries. OBJECTIVES: The aim of this study was to determine the prevalence of HPV infection and its genotype distribution among Iranian males. PATIENTS AND METHODS: Between March 2009 and April 2014, a total number of 483 males, referred to Iran University of Medical Sciences-affiliated sexually transmitted infections (STI) clinics, were enrolled in this study. Following DNA extraction, HPV detection and genotyping were performed using INNO-LiPA HPV Genotyping Extra assay. To analyze the association of HPV infection and age, the logistic regression was employed. RESULTS: No statistical association between HPV infection and age was observed (P = 0.469). Furthermore, there was no statistically significant correlation between HR HPV infection and age (P = 0.330). CONCLUSIONS: In this investigation, the prevalence of HPV infection was relatively substantial. Totally, 17 different HPV genotypes were detected and the most frequently detected genotypes were HPV6, HPV11, HPV16, HPV18 and HPV52, respectively. The data from this study is essential for planning future public health strategies including HPV vaccination programs. PMID- 26862389 TI - Allergen immunotherapy for allergic asthma: protocol for a systematic review. AB - BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for Allergic Asthma. We seek to critically assess the effectiveness, cost effectiveness and safety of AIT in the management of allergic asthma. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised. DISCUSSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT. PMID- 26862390 TI - Pig producer perspectives on the use of meat inspection as an animal health and welfare diagnostic tool in the Republic of Ireland and Northern Ireland. AB - BACKGROUND: Currently, there is growing interest in developing ante and post mortem meat inspection (MI) to incorporate measures of pig health and welfare for use as a diagnostic tool on pig farms. However, the success of the development of the MI process requires stakeholder engagement with the process. Knowledge gaps and issues of trust can undermine the effective exchange and utilisation of information across the supply chain. A social science research methodology was employed to establish stakeholder perspectives towards the development of MI to include measures of pig health and welfare. In this paper the findings of semi structured telephone interviews with 18 pig producers from the Republic of Ireland and Northern Ireland are presented. RESULTS: Producers recognised the benefit of the utilisation of MI data as a health and welfare diagnostic tool. This acknowledgment, however, was undermined for some by dissatisfaction with the current system of MI information feedback, by trust and fairness concerns, and by concerns regarding the extent to which data would be used in the producers' interests. Tolerance of certain animal welfare issues may also have a negative impact on how producers viewed the potential of MI data. The private veterinary practitioner was viewed as playing a vital role in assisting them with the interpretation of MI data for herd health planning. CONCLUSIONS: The development of positive relationships based on trust, commitment and satisfaction across the supply chain may help build a positive environment for the effective utilisation of MI data in improving pig health and welfare. The utilisation of MI as a diagnostic tool would benefit from the development of a communication strategy aimed at building positive relationships between stakeholders in the pig industry. PMID- 26862388 TI - Sex dependency of inhibitory control functions. AB - BACKGROUND: Inhibition of irrelevant responses is an important aspect of cognitive control of a goal-directed behavior. Females and males show different levels of susceptibility to neuropsychological disorders such as impulsive behavior and addiction, which might be related to differences in inhibitory brain functions. METHODS: We examined the effects of 'practice to inhibit', as a model of rehabilitation approach, and 'music', as a salient contextual factor in influencing cognition, on the ability of females and males to perform a stop signal task that required inhibition of initiated or planned responses. In go trials, the participants had to rapidly respond to a directional go cue within a limited time window. In stop trials, which were presented less frequently, a stop signal appeared immediately after the go-direction cue and the participants had to stop their responses. RESULTS: We found a significant difference between females and males in benefiting from practice in the stop-signal task: the percentage of correct responses in the go trials increased, and the ability to inhibit responses significantly improved, after practice in females. While listening to music, females became faster but males became slower in responding to the go trials. Both females and males became slower in performing the go trials following an error in the stop trials; however, music significantly affected this post-error slowing depending on the sex. Listening to music decreased post-error slowing in females but had an opposite effect in males. CONCLUSIONC: Here, we show a significant difference in executive control functions and their modulation by contextual factors between females and males that might have implications for the differences in their propensity for particular neuropsychological disorders and related rehabilitation approaches. PMID- 26862392 TI - Basal body structure and cell cycle-dependent biogenesis in Trypanosoma brucei. AB - Basal bodies are microtubule-based organelles that assemble cilia and flagella, which are critical for motility and sensory functions in all major eukaryotic lineages. The core structure of the basal body is highly conserved, but there is variability in biogenesis and additional functions that are organism and cell type specific. Work carried out in the protozoan parasite Trypanosoma brucei has arguably produced one of the most detailed dissections of basal body structure and biogenesis within the context of the flagellar pocket and associated organelles. In this review, we provide a detailed overview of the basic basal body structure in T. brucei along with the accessory structures and show how basal body movements during the basal body duplication cycle orchestrate cell and organelle morphogenesis. With this in-depth three-dimensional knowledge, identification of many basal body genes coupled with excellent genetic tools makes it an attractive model organism to study basal body biogenesis and maintenance. PMID- 26862393 TI - Paramecium tetraurelia basal body structure. AB - Paramecium is a free-living unicellular organism, easy to cultivate, featuring ca. 4000 motile cilia emanating from longitudinal rows of basal bodies anchored in the plasma membrane. The basal body circumferential polarity is marked by the asymmetrical organization of its associated appendages. The complex basal body plus its associated rootlets forms the kinetid. Kinetids are precisely oriented within a row in correlation with the cell polarity. Basal bodies also display a proximo-distal polarity with microtubule triplets at their proximal ends, surrounding a permanent cartwheel, and microtubule doublets at the transition zone located between the basal body and the cilium. Basal bodies remain anchored at the cell surface during the whole cell cycle. On the opposite to metazoan, there is no centriolar stage and new basal bodies develop anteriorly and at right angle from the base of the docked ones. Ciliogenesis follows a specific temporal pattern during the cell cycle and both unciliated and ciliated docked basal bodies can be observed in the same cell. The transition zone is particularly well organized with three distinct plates and a maturation of its structure is observed during the growth of the cilium. Transcriptomic and proteomic analyses have been performed in different organisms including Paramecium to understand the ciliogenesis process. The data have incremented a multi-organism database, dedicated to proteins involved in the biogenesis, composition and function of centrosomes, basal bodies or cilia. Thanks to its thousands of basal bodies and the well-known choreography of their duplication during the cell cycle, Paramecium has allowed pioneer studies focusing on the structural and functional processes underlying basal body duplication. Proteins involved in basal body anchoring are sequentially recruited to assemble the transition zone thus indicating that the anchoring process parallels the structural differentiation of the transition zone. This feature offers an opportunity to dissect spatio temporally the mechanisms involved in the basal body anchoring process and transition zone formation. PMID- 26862394 TI - Scalable linkage-disequilibrium-based selective sweep detection: a performance guide. AB - BACKGROUND: Linkage disequilibrium is defined as the non-random associations of alleles at different loci, and it occurs when genotypes at the two loci depend on each other. The model of genetic hitchhiking predicts that strong positive selection affects the patterns of linkage disequilibrium around the site of a beneficial allele, resulting in specific motifs of correlation between neutral polymorphisms that surround the fixed beneficial allele. Increased levels of linkage disequilibrium are observed on the same side of a beneficial allele, and diminish between sites on different sides of a beneficial mutation. This specific pattern of linkage disequilibrium occurs more frequently when positive selection has acted on the population rather than under various neutral models. Thus, detecting such patterns could accurately reveal targets of positive selection along a recombining chromosome or a genome. Calculating linkage disequilibria in whole genomes is computationally expensive because allele correlations need to be evaluated for millions of pairs of sites. To analyze large datasets efficiently, algorithmic implementations used in modern population genetics need to exploit multiple cores of current workstations in a scalable way. However, population genomic datasets come in various types and shapes while typically showing SNP density heterogeneity, which makes the implementation of generally scalable parallel algorithms a challenging task. FINDINGS: Here we present a series of four parallelization strategies targeting shared-memory systems for the computationally intensive problem of detecting genomic regions that have contributed to the past adaptation of the species, also referred to as regions that have undergone a selective sweep, based on linkage disequilibrium patterns. We provide a thorough performance evaluation of the proposed parallel algorithms for computing linkage disequilibrium, and outline the benefits of each approach. Furthermore, we compare the accuracy of our open-source sweep-detection software OmegaPlus, which implements all four parallelization strategies presented here, with a variety of neutrality tests. CONCLUSIONS: The computational demands of selective sweep detection algorithms depend greatly on the SNP density heterogeneity and the data representation. Choosing the right parallel algorithm for the analysis can lead to significant processing time reduction and major energy savings. However, determining which parallel algorithm will execute more efficiently on a specific processor architecture and number of available cores for a particular dataset is not straightforward. PMID- 26862395 TI - A cause of severe thigh injury: Battery explosion. AB - INTRODUCTION: In parallel with technological improvements, humankind encounter with equipments/devices transforming chemical energy to electrical energy. Especially automobile batteries, watch and mobile phone batteries are the most encountered ones. In the literature, there are mainly facial burn cases due to mobile phone battery explosion. On the other hand very few examples of serious lower limb. injury is present. PRESENTATION OF CASE: 12-year-old female patient referred to emergency room with skin and soft tissue injuries on bilateral anteromedial thigh area as a result of battery explosion. The widest axis of skin defect was approximately 16 * 8 cm on the right side, and 17 * 4 cm on the left side. In addition, there were tattooing caused by chemical injury and multiple pin-point like lesions extending to dermal level on anterior region of thigh. Chemically dirty and necrotized dermal and subdermal tissues were debrided and foreign materials were removed from regions with multiple tattooing. Left thigh was closed primarily. In order to close the defect on right anterior thigh, skin flap from right medial thigh is advanced in Y-V fashion. DISCUSSION: Battery explosion causing lower extremity tissue defect is a type of injury that is rarely seen in the literature. Regardless of battery size and energy level, they should be considered as potential explosive material and protector masks, clothing should be worn during contact with this type of material. PMID- 26862396 TI - Surgical quality in colorectal cancer. AB - OBJECTIVE: To determine the quality of surgical management offered to patients with colorectal cancer (CRC) as measured by adequacy of nodal resections and compare variations across the major hospitals in Jamaica. METHOD: Data was obtained from the CRC Registry of patients diagnosed and treated surgically for CRC during the 3-year period commencing January 1, 2011. Variables analyzed included tumor site, stage and number of lymph nodes resected across hospitals. RESULTS: During the period under review 60% (349) of 586 patients had resections and formed the basis of this study. Of these 49% were treated at the UHWI, 27% from the KPH and STH, 15% from CRH and MRH and 8% from a private laboratory (DPS). Patient distribution was similar at UHWI compared to the others with mean age (61 vs 62) and with slightly more women having surgery (53% Vs 54%) (UHWI vs Others). For tumor grade, margin status, lymphovascular and depth of invasion (majority T3) there was no difference between UHWI and the other sites, although a smaller percentage of tumors treated at UHWI had Crohn's like reaction (p = 0.01). There was a larger proportion of sigmoid cancer at UHWI while the reverse trend was seen in cancers of the rectum (p = 0.027). The tumors treated at UHWI have a larger median number of regional nodes when compared to the other facilities (14 vs 10; p < 0.001) and also more likely to have positive nodes, as were women and younger patients. Comparison across facilities revealed that the proportion of tumors classed as well differentiated, circumferential margin involvement, and having lymphovascular invasion were higher for specimens processed at the private facility (p = 0.021, 0.035, 0.01 respectively). Histopathology reports of tumors treated at UHWI and DPS had median 14 and 18 nodes respectively while at NPH laboratory and CRH they were 9 and 10 respectively (p < 0.001), whilst those of the ascending, descending, sigmoid colon and rectum had median 15, 11, 13, 11 nodes respectively (p < 0.001). CONCLUSIONS: This review demonstrates measurable differences in the surgery and histopathological reports for CRC patients treated across the island. Given adjuvant treatment and prognostic implications there is room for improvement. PMID- 26862397 TI - Transcriptional response of porcine skeletal muscle to feeding a linseed-enriched diet to growing pigs. AB - BACKGROUND: To investigate the effect of feeding a linseed-enriched diet to growing-finishing pigs on gene expression in skeletal muscle, pigs were fed with a linseed-enriched diet for 0, 30, 60 and 90 d. Transcriptional profiles of longissimus dorsi muscle were measured using Affymetrix Genechip. RESULTS: Results showed that 264 genes were identified as differentially expressed genes (DEGs). The strongest transcriptional response was clearly observed at 30 d. DEGs were assigned to several main functional terms, including transcription, apoptosis, intracellular receptor-mediated signaling, muscle organ development, fatty acid metabolic process, cell motion, regulation of glucose metabolic process, spermatogenesis and regulation of myeloid cell differentiation. We also found that transcriptional changs of several transcription cofactors might contribute to n-3 PUFAs regulated gene expression. In addition, the increased expression of IGF-1, insulin signaling pathway and the metabolism of amino acids might involve in the muscle growth induced by feeding a linseed-enriched diet. The results also provide the new evidence that the expression changes of PTPN1, HK2 and PGC-1alpha might contribute to the regulation of insulin sensitivity by n 3 PUFAs. CONCLUSIONS: Our finding provided correlative evidence that feeding the linseed enriched diet affact expression of genes involved in insulin signaling pathway and the metabolism of amino acids. PMID- 26862398 TI - Extrahepatic manifestations of chronic hepatitis C virus infection. AB - During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined. PMID- 26862401 TI - Thigh compartment syndrome complicated by sciatic nerve palsy, rhabdomyolysis, and acute renal failure. AB - We reported a rare case of thigh compartment syndrome (TCS) complicated by sciatic nerve palsy, rhabdomyolysis, and acute renal failure in an alcoholic patient. Intensive care measures and immediate posteromedial decompressive fasciotomy were performed. These timely interventions resulted in improvement of the nerve injury and restoration of the kidney function. PMID- 26862399 TI - Carbapenem resistance: overview of the problem and future perspectives. AB - Carbapenem resistance, mainly among Gram-negative pathogens, is an ongoing public health problem of global dimensions. This type of antimicrobial resistance, especially when mediated by transferable carbapenemase-encoding genes, is spreading rapidly causing serious outbreaks and dramatically limiting treatment options. In this article, important key points related to carbapenem resistance are reviewed and future perspectives are discussed. PMID- 26862403 TI - The curled sebaceous horn. AB - The mysterious sebaceous horn (devil's horn) is a historically perplexing phenomenon of unknown etiology. It classically occurs on the sun-exposed areas of the face and hands and consists of a keratin mound with a benign base in most cases and squamous cell carcinoma occurring in about 20% of patients. PMID- 26862402 TI - Large-scale mitochondrial DNA deletion underlying familial multiple system atrophy of the cerebellar subtype. AB - A family with mitochondrial inheritance of multiple system atrophy of the cerebellar subtype. MRI brain shows significant cerebellar atrophy with mild pontine atrophy and the classical hot cross bun sign in Pons. The muscle biopsy was indicative of mitochondrial myopathy. Mitochondrial DNA analysis revealed a low-level large mtDNA deletion, m.3264_1607del12806 bp. PMID- 26862404 TI - Progressive scarring facial lesions in a boy. AB - Hydroa vacciniforme is a photosensitivity disorder characterized by the childhood onset of necrotic vesiculopapules on exposed areas. We present a case of a 10 year-old boy with a 1-year history of papular lesions over his face. In this report, we discuss the in-depth histology of hydroa vacciniforme, and the management options. PMID- 26862400 TI - Recent advances in the understanding of antibiotic resistance in Clostridium difficile infection. AB - Clostridium difficile epidemiology has changed in recent years, with the emergence of highly virulent types associated with severe infections, high rates of recurrences and mortality. Antibiotic resistance plays an important role in driving these epidemiological changes and the emergence of new types. While clindamycin resistance was driving historical endemic types, new types are associated with resistance to fluoroquinolones. Furthermore, resistance to multiple antibiotics is a common feature of the newly emergent strains and, in general, of many epidemic isolates. A reduced susceptibility to antibiotics used for C. difficile infection (CDI) treatment, in particular to metronidazole, has recently been described in several studies. Furthermore, an increased number of strains show resistance to rifamycins, used for the treatment of relapsing CDI. Several mechanisms of resistance have been identified in C. difficile, including acquisition of genetic elements and alterations of the antibiotic target sites. The C. difficile genome contains a plethora of mobile genetic elements, many of them involved in antibiotic resistance. Transfer of genetic elements among C. difficile strains or between C. difficile and other bacterial species can occur through different mechanisms that facilitate their spread. Investigations of the fitness cost in C. difficile indicate that both genetic elements and mutations in the molecular targets of antibiotics can be maintained regardless of the burden imposed on fitness, suggesting that resistances may persist in the C. difficile population also in absence of antibiotic selective pressure. The rapid evolution of antibiotic resistance and its composite nature complicate strategies in the treatment and prevention of CDI. The rapid identification of new phenotypic and genotypic traits, the implementation of effective antimicrobial stewardship and infection control programs, and the development of alternative therapies are needed to prevent and contain the spread of resistance and to ensure an efficacious therapy for CDI. PMID- 26862406 TI - Pulmonary vein and cavotricuspid isthmus ablation in situs inversus totalis. AB - Pulmonary vein isolation (PVI) with cavotricuspid isthmus (CTI) ablation is feasible in patients with situs inversus totalis. Orientation challenges are improved with the use of electroanatomical mapping prior to transseptal puncture. Care must be taken to note the opposing anatomic locations of important structures such as the left atrial appendage, descending aorta, and phrenic nerve. PMID- 26862405 TI - Swallowing-induced atrial tachycardia: case report. AB - A 53-year-old man presented with heart palpitations while swallowing. Electrophysiologic study (EPS) and immunohistochemical results of his esophageal leiomyoma suggested that swallowing-induced atrial tachycardia is related with neural reflex. S100-immunopositive nerve fibers are demonstrated sympathetic nerves which possibly explain the mechanism. Metoprolol tartrate tablets are effective in our patient. PMID- 26862407 TI - Infectious endocarditis due to Streptococcus pneumoniae in a cardiac surgery patient: a new form of clinical presentation. AB - High mortality associated with pneumococcal endocarditis is due to late diagnosis and the frequency of complications, which usually require early diagnostic and intensive therapeutic measures. We present the first reported case of pneumococcal endocarditis with simultaneous infection of an aortic prosthetic valve, native tricuspid valve, and permanent pacemaker lead. PMID- 26862408 TI - A case of leukemic retinopathy mimicking common ischemic retinopathies. AB - Reported case of leukemic retinopathy mimicking common ischemic retinopathies in a young adult where ophthalmic visit was the first step to the diagnosis of chronic myeloid leukemia. It highlights the importance of routine eye exams and that clinicians should suspect leukemia in an otherwise healthy patient presenting with ischemic retinopathy. PMID- 26862409 TI - Hypertrichosis cubiti, a case report and literature review. AB - Hypertrichosis cubiti is an uncommon congenital hypertrichosis with links to genetic syndromes, both autosomal dominant and recessive, with variable penetrance and expressivity. It may also present in sporadic cases with no phenotypic abnormalities or family history. PMID- 26862410 TI - Warfarin treatment and antifungal agent caspofungin for severe fungal infection in a patient previously treated with radiotherapy for oropharyngeal cancer. AB - Drug-Drug interactions is important when caring for warfarin-treated patients. We examined the impact on INR with coadministration of warfarin and caspofungin and showed no affect on the INR. Coadministrations of fluconazole lead to a marked increase in INR. We concluded that administration of caspofungin and warfarin was safe. PMID- 26862411 TI - A seven weeks old baby with diabetic ketoacidosis: a case report. AB - Diabetes mellitus is rare during infancy, however, it should be suspected in infants presenting with features consistent with sepsis and hyperglycemia. This is crucial in initiating the treatment of diabetes ketoacidosis which if delayed may result in significant morbidity and death. PMID- 26862412 TI - Accumulative eschar after burn. AB - Eschar formation is a potential sequela of burn injuries. Definitive management may include escharectomy and eschar debridement. After eschar removal, the wound can be covered with a skin graft or reepithelialization. For prolonged refractory eschar on the fingertips, topical use of rb-bFGF after debridement can achieve an optimal outcome. PMID- 26862413 TI - Ogilvie's syndrome after rectal prolapse repair and total hemorrhoidectomy: Case report and Discussion. AB - This case highlights the rare diagnosis of Ogilvie's syndrome after minor surgery in a private hospital where facilities and expertise are generally sparse. It shows the importance of knowledge of the subject, proper assessment, accurate diagnosis, and early input from seniors is crucial to prevent ischemia and perforation of colon that carries high mortality. PMID- 26862414 TI - Acute stroke from paradoxical embolism of dense fibrous tissue following pacemaker lead extraction: salvation by mechanical thrombectomy. AB - Systemic embolization is a dreaded complication of transvenous lead extraction (TLE), even without visible vegetations. Preoperative patent foramen ovale evaluation is important, justifying neurological surveillance or consideration of surgical extraction in selected cases. In case of stroke after TLE, mechanical thrombectomy is a successful therapy, and should be readily available. PMID- 26862415 TI - Inferior vena cava filter thrombosis. AB - Patients with inferior vena cava (IVC) filters - particularly permanent filters - are at increased risk for recurrent deep venous thrombosis (DVT). Judicious use of IVC filters, as well as the prompt retrieval of temporary IVC filters, substantially reduces the risk of IVC thrombosis. PMID- 26862416 TI - Adult hemophagocytic lymphohistiocytosis causing multi organ dysfunction in a patient with multiple autoimmune disorders: when the immune system runs amok. AB - We report a case of several autoimmune disorders eventually presenting as severe multi organ dysfunction syndrome caused by adult hemophagocytic lymphohistiocytosis (HLH). Clinical and laboratory tests might lead to fatal misinterpretation without awareness of its diagnostic evaluation, as HLH shares common features with sepsis and immune-mediated systemic inflammatory response syndromes. PMID- 26862417 TI - Cancer-associated retinopathy as the leading symptom in colon cancer. AB - Cancer-associated retinopathy (CAR) is a rare paraneoplastic visual syndrome. Its early detection may lead to the diagnosis of the causative malignancy. As many different types of malignancies are known to be associated with CAR, it is important that clinicians are aware of the phenomenon of CAR. PMID- 26862418 TI - Mild phenotype in an adult male with X-linked adrenoleukodystrophy - case report. AB - X-linked adrenoleukodystrophy may present with a deceptively mild phenotype, even in adult males. Tight collaboration between clinicians, geneticists, biochemists, and other specialists is increasingly required for clarification of diagnosis in cases with atypical presentation. PMID- 26862419 TI - Ataxia and focal dystonia in Kallmann syndrome. AB - A case of Kallmann syndrome (KS) associated with rare neurological manifestations is presented. Cerebellar ataxia probably caused by a small posterior fossa and a focal dystonia affecting the left lower limb expand the spectrum of neurological manifestations occurring in KS. Further studies are needed to better understand these manifestations. PMID- 26862420 TI - An elderly female with rib osteolytic lesion after recovery from fulminant liver failure induced by acute-onset autoimmune hepatitis. AB - This report highlights an interesting case of an osteolytic lesion (actinomycosis) after fulminant liver failure induced by autoimmune hepatitis (AIH). When treating patients with fulminant liver failure due to AIH using immunosuppressive drugs, such as steroids, the possibility of such rare occurrences should be kept in mind. PMID- 26862421 TI - A rare case of orthostatic headache due to spontaneous intracranial hypotension. AB - Headache is one of the most common clinical entities, and has a long list of differential diagnoses; however, one of the more uncommon causes of postural headache is spontaneous intracranial hypotension. It is important that clinicians be aware of this condition, as it is often overlooked, leading to invasive and unnecessary diagnostic testing. A good history and physical exam, paired with an MRI of the brain is sufficient to make the diagnosis of SIH, relieve the symptomology of the patient in a quick and efficient manner, and avoid costly invasive procedures. PMID- 26862422 TI - Enlarging mediastinal/hilar lymphadenopathy with calcification. AB - A 77-year-old man was referred to our hospital due to enlarging mediastinal/hilar lymphadenopathy with calcification. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and bone marrow aspiration were performed. Subsequently, monoclonal gammopathy of undetermined significance (MGUS) associated with mediastinal amyloidosis was diagnosed. We hereby report a case in which EBUS-TBNA led to a successful diagnosis of amyloidosis. PMID- 26862423 TI - Sister Mary Joseph nodule. AB - Umbilical tumors are relatively rare and can be classified as benign or malignant. The term "Sister Mary Joseph nodule" is used to describe an umbilical neoplasm associated with advanced metastatic intra-abdominal malignancy. It generally has a poor prognosis. PMID- 26862426 TI - Anesthesia for patients with subglottic cysts. AB - Acquired subglottic cysts can cause rapid development of respiratory distress. Subglottic cysts are a disease of premature infants and other pathologies of prematurity should be anticipated. Perioperative success is dependent on communication between surgeon and anesthesiologist. Contingency plans for an emergency surgical airway should be in place in the event of total airway obstruction. PMID- 26862424 TI - Complete resolution of non-necrotizing lung granuloma and pyoderma gangrenosum after restorative proctocolectomy in a woman with severe ulcerative colitis and cytomegalovirus infection. AB - Here, we report the unusual case of an ulcerative colitis female patient presenting together with cytomegalovirus infection, pyoderma gangrenosum and a noncaseating lung granuloma, both resistant to immunomodulatory drugs which dramatically obtained a clinical stable remission after restorative proctocolectomy. PMID- 26862425 TI - Maintaining a viable vascular access for hemodialysis in an elderly person with diabetes: a journey to live, not just to stay alive. AB - The longevity of a successful vascular access (VA) is enhanced when the care of the patient's VA is the responsibility of everyone involved, including the patient and their family. A family nursing perspective enhances VA care outcomes and increases quality of life and well-being for patients requiring hemodialysis. PMID- 26862427 TI - Penetrating neck injuries: the point of plain films. AB - Plain films aid management and do not delay the emergency treatment of a stable patient with penetrating neck trauma in the resuscitation room and thus should be taken while arranging CT angiography. PMID- 26862429 TI - Facklamia hominis scapula abscess, Marseille, France. AB - Facklamia hominis is a Gram-positive bacterium that was first isolated from various human samples, excluding abscesses of the scapula. We here report the first scapular abscess infection due to F. hominis, found in Marseille, France. We also reviewed all cases published in the literature. PMID- 26862428 TI - Prevalence of Chlamydia trachomatis, Ureaplasma spp., Mycoplasma genitalium and Mycoplasma hominis among outpatients in central Greece: absence of tetracycline resistance gene tet(M) over a 4-year period study. AB - A total of 301 men and women attending local urologists and gynaecologists in the state of Thessaly, central Greece, were tested for Chlamydia trachomatis, Ureaplasma spp., Mycoplasma genitalium and Mycoplasma hominis DNA. Investigation of the tet(M) gene, which confers tetracycline resistance in these genera, was also performed. Low incidence of C. trachomatis and Mycoplasma spp. as well as high prevalence of Ureaplasma spp., especially among women, were found. The tet(M) gene was absent in all cases, notably in a region where doxycycline administration remains the first therapeutic option unless special medical conditions direct otherwise. PMID- 26862430 TI - Noncontiguous finished genome sequence and description of Kallipyga gabonensis sp. nov. AB - Taxonogenomics coupled with culturomics promotes the isolation and characterization of bacteria. Kallipyga gabonensis sp. nov. strain GM4 is a strictly anaerobic, Gram-positive, and non motile coccus isolated from the stool of a Gabonese male teenager. The genome is 1,621,211 bp long with 50.01% G+C content and two scaffolds. Of the 1,536 predicted genes, 1,475 were protein coding genes and 61 were RNA genes. A total of 931 genes were assigned a putative function, and 79 genes were identified as ORFans. PMID- 26862431 TI - Persistence of nasal colonization with human pathogenic bacteria and associated antimicrobial resistance in the German general population. AB - The nares represent an important bacterial reservoir for endogenous infections. This study aimed to assess the prevalence of nasal colonization by different important pathogens, the associated antimicrobial susceptibility and risk factors. We performed a prospective cohort study among 1878 nonhospitalized volunteers recruited from the general population in Germany. Participants provided nasal swabs at three time points (each separated by 4-6 months). Staphylococcus aureus, Enterobacteriaceae and important nonfermenters were cultured and subjected to susceptibility testing. Factors potentially influencing bacterial colonization patterns were assessed. The overall prevalence of S. aureus, Enterobacteriaceae and nonfermenters was 41.0, 33.4 and 3.7%, respectively. Thirteen participants (0.7%) were colonized with methicillin resistant S. aureus. Enterobacteriaceae were mostly (>99%) susceptible against ciprofloxacin and carbapenems (100%). Extended-spectrum beta-lactamase-producing isolates were not detected among Klebsiella oxytoca, Klebsiella pneumoniae and Escherichia coli. Several lifestyle- and health-related factors (e.g. household size, travel, livestock density of the residential area or occupational livestock contact, atopic dermatitis, antidepressant or anti-infective drugs) were associated with colonization by different microorganisms. This study unexpectedly demonstrated high nasal colonization rates with Enterobacteriaceae in the German general population, but rates of antibiotic resistance were low. Methicillin resistant S. aureus carriage was rare but highly associated with occupational livestock contact. PMID- 26862433 TI - Molecular detection of CTX-M-15-type beta-lactamases in Escherichia coli strains from Senegal. AB - We aimed to detect the extended-spectrum beta-lactamases (ESBLs) secreted by clinical strains of Escherichia coli at Fann University Hospital in Dakar and to characterize them molecularly. We identified 32 isolates producing ESBLs. The CTX M-15 gene was the most frequently detected ESBL gene, detected in 90.63% of the isolates studied. PMID- 26862432 TI - Noncontiguous finished genome sequence and description of Gabonia massiliensis gen. nov., sp. nov. AB - Culturomics coupled with taxonogenomics is currently used to isolate and characterize new bacteria. Here we describe the features and complete genome sequence of Gabonia massiliensis strain GM3, an anaerobic Gram negative, non spore-forming and catalase-positive bacillus isolated from a stool specimen of a healthy Gabonese male youth. Belonging to a new genus called Gabonia, it exhibits a genome of 4 261 752 bp including 37.9% GC content and 3,288 predicted genes. PMID- 26862435 TI - Relapsing sepsis episodes of Escherichia coli with CTX-M ESBL or derepressed ampC genes in a patient with chronic autoimmune pancreatitis complicated by IgG4 hypergammaglobulinaemia. AB - Bloodstream recurrent infections have been reported for a variety of opportunistic bacteria. These are often either catheter related or are caused by indwelling devices. A case of relapsing sepsis with two Escherichia coli strains carrying extended-spectrum beta-lactamase and derepressed ampC genes is reported. The patient had seven episodes of bloodstream infections within 1 year and was diagnosed with chronic autoimmune pancreatitis and IgG4 hypergammaglobulinaemia. Abscesses were found in his spleen and pancreas cauda, which was finally resected. Relapses of bacteraemia with resistant enterobacteria should be considered during perioperative protection. Surgical removal of the infective focus could be curative. PMID- 26862434 TI - Enterococcus faecium small colony variant endocarditis in an immunocompetent patient. AB - Small colony variants (SCV) are slow-growing subpopulations of bacteria usually associated with auxotrophism, causing persistent or recurrent infections. Enterococcus faecalis SCV have been seldom described, and only one case of Enterococcus faecium SCV has been reported, associated with sepsis in a leukaemia patient. Here we report the first case described of bacteraemia and endocarditis by SCV E. faecium in an immunocompetent patient. PMID- 26862437 TI - Report of the first Vagococcus lutrae human infection, Marseille, France. AB - Vagococcus lutrae is a Gram-positive coccus initially isolated from the common otter (Lutra lutra) but that has never been reported as a human pathogen. We describe the first case of human infection due to Vagococcus lutrae in Marseille, France. PMID- 26862436 TI - First report of sepsis due to Catabacter hongkongensis in an Italian patient. AB - The first isolation of Catabacter hongkongensis in Italy is reported. Pleomorphic Gram-positive rods were grown in blood cultures from samples obtained from a 55 year-old patient admitted to the intensive care unit with sepsis after he experienced massive thoracic and abdominal trauma. The identification was obtained by amplification and sequencing of the 16S rRNA gene. PMID- 26862438 TI - Governance and pharmacovigilance in Brazil: a scoping review. AB - BACKGROUND: This scoping review investigates the relationship between governance, pharmacovigilance, and Agencia Nacional de Vigilancia Sanitaria (ANVISA) in Brazil, which has authority over Brazil's national pharmaceutical policy, drug registration and coordination of the national pharmacovigilance system. The purpose is to investigate opportunities for effective pharmacovigilance. METHODS: Sixty-three terms pertaining to pharmacovigilance in Brazil and ANVISA, global institutions, pharmaceutical industry, and civil society were searched in thirteen relevant databases on November 17-18, 2013. Using a pharmacogovernance framework we analyzed ANVISA's pharmacogovernance: the manner in which governing structures, policy instruments, and institutional authority are managed to promote societal interests for patient safety due to medication use. The integration of transnational policy ideas for regulatory governance into pharmacogovernance in Brazil was also investigated. RESULTS: Brazil's policy, laws, and regulations support ANVISA's authority to ensure access to safe medicines and health products however ANVISA's broad mandate and gaps in pharmacogovernance account for regional disparities in monitoring and assessing drug safety. Gaps in pharmacogovernance include: equity and inclusiveness; stakeholder coordination; effectiveness and efficiency; responsiveness; and intelligence and information. CONCLUSIONS: Pharmacogovernance that addresses 1) regional resource disparities, 2) federal and state lack of coordination of pharmacovigilance regulations, 3) asymmetric representation in the pharmaceutical regulatory agenda and which 4) disaggregates regulatory authority over health and commercial sectors would strengthen pharmacovigilance in Brazil. PMID- 26862441 TI - "True" posterior communicating aneurysms: Three cases, three strategies. AB - BACKGROUND: The authors provide a review of true aneurysms of the posterior communicating artery (PCoA). Three cases admitted in our hospital are presented and discussed as follows. CASE DESCRIPTIONS: First patient is a 51-year-old female presenting with a Fisher II, Hunt-Hess III (headache and confusion) subarachnoid hemorrhage (SAH) from a ruptured true aneurysm of the right PCoA. She underwent a successful ipsilateral pterional craniotomy for aneurysm clipping and was discharged on postoperative day 4 without neurological deficit. Second patient is a 53-year-old female with a Fisher I, Hunt-Hess III (headache, mild hemiparesis) SAH and multiple aneurisms, one from left ophthalmic carotid artery and one (true) from right PCoA. These lesions were approached and successfully treated by a single pterional craniotomy on the left side. The patient was discharged 4 days after surgery, with complete recovery of muscle strength during follow-up. Third patient is a 69-year-old male with a Fisher III, Hunt-Hess III (headache and confusion) SAH, from a true PCoA on the right. He had a left subclavian artery occlusion with flow theft from the right vertebral artery to the left vertebral artery. The patient underwent endovascular treatment with angioplasty and stent placement on the left subclavian artery that resulted in aneurysm occlusion. CONCLUSION: In conclusion, despite their seldom occurrence, true PCoA aneurysms can be successfully treated with different strategies. PMID- 26862440 TI - Perillyl alcohol: Dynamic interactions with the lipid bilayer and implications for long-term inhalational chemotherapy for gliomas. AB - BACKGROUND: Gliomas display a high degree of intratumor heterogeneity, including changes in physiological parameters and lipid composition of the plasma membrane, which may contribute to the development of drug resistance. Biophysical interactions between therapeutic agents and the lipid components at the outer plasma membrane interface are critical for effective drug uptake. Amphipathic molecules such as perillyl alcohol (POH) have a high partition coefficient and generally lead to altered lipid acyl tail dynamics near the lipid-water interface, impacting the lipid bilayer structure and transport dynamics. We therefore hypothesized that glioma cells may display enhanced sensitivity to POH induced apoptosis due to plasma membrane alterations, while in non-transformed cells, POH may be expelled through thermal agitation. METHODS: Interactions between POH and the plasma membrane was studied using molecular dynamics simulations. In this phase I/II trial, we set up to evaluate the clinical effectiveness of long-term (up to 5 years) daily intranasal administration of POH in a cohort of 19 patients with low-grade glioma (LGG). Importantly, in a series of clinical studies previously published by our group, we have successfully established that intranasal delivery of POH to patients with malignant gliomas is a viable and effective therapeutic strategy. RESULTS: POH altered the plasma membrane potential of the lipid bilayer of gliomas and prolonged intranasal administration of POH in a cohort of patients with LGG halted disease progression with virtually no toxicity. CONCLUSION: Altogether, the results suggest that POH induced alterations of the plasma membrane might be contributing to its therapeutic efficacy in preventing LGG progression. PMID- 26862442 TI - Delayed intraventricular metastasis of clival chordoma. PMID- 26862443 TI - The time course changes in expression of aquaporin 4 and aquaporin 1 following global cerebral ischemic edema in rat. AB - BACKGROUND: The aim of this global cerebral ischemia study was to study the changes in expression levels of aquaporin 4 (AQP4) and AQP1 over time. METHODS: Sprague-Dawley type male rats were divided into six groups. Sham group and ischemia/reperfusion were performed on five other groups using the four-vessel occlusion model. Reperfusion was done 30 min after the occlusion, and each group was tested at 1, 6, 12, 24, and 48 h for brain wet-dry weight ratio and AQP4 and AQP1 expression levels using immunohistochemistry. To prove ischemia development exists in both hippocampal neurons and epithelia of choroid plexus, hematoxylin, and eosin and neuronal marker (NeuN) immune-staining have been applied to the sham experimental group at 48 h. AQP4 expression levels are also measured with western blotting. RESULTS: After ischemia/reperfusion it is observed that the decrease in brain water content between 12 and 24 h was statistically significant (P < 0.01). In parallel and based on immunohistochemical staining, AQP4 expression levels did not exhibit any statistically significant change. AQP4 levels did not show any statistically significant change in western blotting. AQP1 expression in choroid plexus epithelial cells decreased at the 12 and 24 h but increased in 48 h (P < 0.05). CONCLUSIONS: Lack of change in AQP4 expression levels is thought as its dual role in formation and elimination of ischemic brain edema. Decrease in AQP1 expression levels in 24 h can be explained with necrosis in choroid plexus after ischemia and the increase in 48 h mark can be related to recovery in choroid plexus. PMID- 26862439 TI - Neuroplasticity and Repair in Rodent Neurotoxic Models of Spinal Motoneuron Disease. AB - Retrogradely transported toxins are widely used to set up protocols for selective lesioning of the nervous system. These methods could be collectively named "molecular neurosurgery" because they are able to destroy specific types of neurons by using targeted neurotoxins. Lectins such as ricin, volkensin, or modeccin and neuropeptide- or antibody-conjugated saporin represent the most effective toxins used for neuronal lesioning. Some of these specific neurotoxins could be used to induce selective depletion of spinal motoneurons. In this review, we extensively describe two rodent models of motoneuron degeneration induced by volkensin or cholera toxin-B saporin. In particular, we focus on the possible experimental use of these models to mimic neurodegenerative diseases, to dissect the molecular mechanisms of neuroplastic changes underlying the spontaneous functional recovery after motoneuron death, and finally to test different strategies of neural repair. The potential clinical applications of these approaches are also discussed. PMID- 26862444 TI - A case of ruptured infectious anterior cerebral artery aneurysm treated by interposition graft bypass using the superficial temporal artery. AB - BACKGROUND: To describe the application of an interposition graft bypass using superficial temporal artery (STA) for the treatment of a ruptured anterior cerebral artery (ACA) infectious aneurysm. CASE DESCRIPTION: A 30-year-old male suffered from severe headache with high fever. The patient's diagnosis was ruptured infectious ACA aneurysm at the A3 segment with a maximum diameter of 4.5 mm, caused by infectious endocarditis. The patient was initially treated with high-dose intravenous antibiotics. Follow-up digital subtraction angiography (DSA) revealed that the fusiform aneurysm had enlarged to a maximum diameter of 14.0 mm. A left paracentral artery, supplying the motor area of the left lower extremity, originated from the body of this aneurysm. Because the angiographic findings suggested a risk of recurrent bleeding, the patient underwent open surgery. Interposition graft bypass using the STA was performed to reconstruct the left A3 segment in an end-to-side manner (left proximal callosomarginal artery - STA graft - left distal pericallosal artery). Then, the origin of the left paracentral artery was cut and anastomosed to the STA graft in an end-to side manner. The affected parent artery was trapped, and the aneurysm was resected. Postoperative magnetic resonance imaging showed no ischemic or hemorrhagic complications, and postoperative DSA revealed the patency of the interposition graft. Pathological diagnosis of the resected aneurysm revealed features corresponding to infectious cerebral aneurysm. The postoperative course was uneventful, and the patient was discharged without any neurological deficits. CONCLUSION: In the treatment of infectious cerebral aneurysms, revascularization should be considered when the affected artery supplies the eloquent area. Interposition graft bypass using the STA is one of the options for revascularization surgery for the treatment of infectious ACA aneurysms. PMID- 26862445 TI - A Syrian neurosurgeon's journey. PMID- 26862446 TI - Cerebellopontine angle primitive neuroectodermal tumor mimicking trigeminal schwannoma. AB - BACKGROUND: Primitive neuroectodermal tumors (PNETs) comprise a group of aggressive, poorly differentiated embryonal tumors occurring in central nervous system as well as in peripheral locations. Primary cerebellopontine angle (CPA) PNET is an extremely rare entity. It is important to have knowledge of this pathology and to be able to differentiate it from other commonly occurring CPA tumors, such as vestibular and trigeminal schwannomas. This distinction is essential because of the difference in the overall treatment plan and prognosis. CASE DESCRIPTION: This report describes a case of a young male presenting with diplopia and numbness of face; magnetic resonance imaging showed a CPA mass. With a provisional diagnosis of trigeminal schwannoma, the patient underwent surgery. Histopathology provided a diagnosis of PNET. CONCLUSION: We discuss the importance of recognizing this rare condition and how this entity differs from the commonly occurring tumors. PMID- 26862447 TI - A simple bracing technique to correct kinking of arterial branches to avoid ischemic sequelae during neurovascular surgery. AB - BACKGROUND: During microscopic procedures for neurovascular disease, we sometimes encounter kinking of arterial branches resulting in ischemic sequelae. A simple and useful technique that involves inserting a small, ball-like prosthesis made of oxidized cellulose or shredded Teflon with fibrin glue that corrects the arterial branch kinking and avoids subsequent compromise is reported. METHODS: Between January and December 2014, three patients developed arterial kinking during microscopic procedures, including two in the caudal loop of the posterior inferior cerebellar artery during microvascular decompression for glossopharyngeal neuralgia and one in a branch of the middle cerebral artery (MCA) during clipping for an unruptured MCA aneurysm. Blood flow insufficiency was confirmed by microvascular Doppler ultrasonography (MDU) and indocyanine green (ICG) videoangiography. The prosthesis, which was made of shredded Teflon in two cases and oxidized cellulose in one case, was inserted into the crotch of the kinked arteries to correct the kinking of the arteries and restore the proper vascular shape and normal blood flow. RESULTS: The small, ball-shaped prosthesis corrected the kinked arteries and maintained the proper shape, which was confirmed by ICG videoangiography and MDU during the operation and three dimensional computerized tomography angiography postoperatively. Postoperatively, the patients did not manifest any ischemic sequelae related to the kinked arteries. CONCLUSION: The insertion of prostheses with fibrin glue into the crotch of a kinked artery for repair is considered a simple and useful method for correcting a kinked artery that avoids ischemic sequelae. PMID- 26862448 TI - A new case of cervical intramedullary sinus histiocytosis causing paraplegia and review of the literature. AB - BACKGROUND: Rosai-Dorfman disease (RDD) is an uncommon, benign histiocytic proliferative disorder of unknown origin. It predominantly affects the lymph nodes, but can also be found extranodal in different organs. Nervous system involvement is rare, and the most cases are intracranial. Surgical treatment is indicated when the central nervous system (CNS) in compromised. CASE DESCRIPTION: We herein describe the management of a 27-year-old woman who presented progressive spinal cord symptoms, secondary to an isolated intramedullary lesion, which had a histological confirmation of RDD. To our knowledge, this is the 6(th) case reported in English written manuscripts. We review these cases and analyze some of the literature concerning the disease. CONCLUSIONS: RDD shows some variability in the involvement of the entire neuraxis, and because its ability to mimic meningeal and primary brain tumors, it is essential to be aware of this entity and consider RDD in the differential diagnosis of various lesions of the CNS. The conclusive diagnosis must be obtained by histological methods, so surgical approaches have to be discussed. Although it is not considered as a malignancy, options for postoperative medical treatment are variable and include radiation, chemotherapy or maybe monoclonal antibodies for refractory or recurrent cases. PMID- 26862450 TI - Human head transplantation. Where do we stand and a call to arms. PMID- 26862449 TI - Ruptured anterior spinal artery aneurysm from a herniated cervical disc. A case report and review of the literature. AB - BACKGROUND: Subarachnoid hemorrhage (SAH) caused by a ruptured cervical anterior spinal artery aneurysm is extremely rare and in the setting of cervical spondylosis. This case presentation reviews the diagnosis, management, and treatment of such aneurysms. CASE PRESENTATION: An 88-year-old female presented with the worst headache of her life without focal deficits. She was found to have diffuse SAH in the basal cisterns extending inferiorly down the spinal canal. Review of the neurodiagnostic images revealed an anterior spinal artery aneurysm in the setting of cervical spondylosis. CONCLUSIONS: Clinicians should be suspicious of cervical spondylosis as a rare etiology for an SAH when cerebral angiograms prove negative for intracranial aneurysms. PMID- 26862451 TI - Solid hemangioblastoma in the cerebellopontine angle: Importance of external carotid blood supply with regard to the probable site of origin and preoperative embolization. AB - BACKGROUND: Hemangioblastoma (HBL) is rare in the cerebellopontine angle (CPA) with questionable origin and limited access for circumferential dissection and "en-bloc" excision. We report a case of surgical removal of large solid CPA-HBL and discuss the pattern of blood supply suggesting its origin and indicating preoperative embolization. CASE DESCRIPTION: The solid and highly vascular CPA HBL had feeders mainly from neuromeningeal division of ascending pharyngeal branch of external carotid artery, suggesting true extra-axial origin. We could achieve "en-bloc" excision without significant blood loss or morbidity using preoperative embolization. CONCLUSION: Large solid HBL is rare in CPA necessitating arduous "en-bloc" excision. The pattern of blood supply probably indicates the site of origin and safety of preoperative embolization. PMID- 26862452 TI - Combined supra-transorbital keyhole approach for treatment of delayed intraorbital encephalocele: A minimally invasive approach for an unusual complication of decompressive craniectomy. AB - BACKGROUND: Intraorbital encephalocele is a rare entity characterized by the herniation of cerebral tissue inside the orbital cavity through a defect of the orbital roof. In patients who have experienced head trauma, intraorbital encephalocele is usually secondary to orbital roof fracture. CASE DESCRIPTION: We describe here a case of a patient who presented an intraorbital encephalocele 2 years after severe traumatic brain injury, treated by decompressive craniectomy and subsequent autologous cranioplasty, without any evidence of orbital roof fracture. The encephalocele removal and the subsequent orbital roof reconstruction were performed by using a modification of the supraorbital keyhole approach, in which we combine an orbital osteotomy with a supraorbital minicraniotomy to facilitate view and access to both the anterior cranial fossa and orbital compartment and to preserve the already osseointegrated autologous cranioplasty. CONCLUSIONS: The peculiarities of this case are the orbital encephalocele without an orbital roof traumatic fracture, and the combined minimally invasive approach used to fix both the encephalocele and the orbital roof defect. Delayed intraorbital encephalocele is probably a complication related to an unintentional opening of the orbit during decompressive craniectomy through which the brain herniated following the restoration of physiological intracranial pressure gradients after the bone flap repositioning. The reconstruction of the orbital roof was performed by using a combined supra transorbital minimally invasive approach aiming at achieving adequate surgical exposure while preserving the autologous cranioplasty, already osteointegrated. To the best of our knowledge, this approach has not been previously used to address intraorbital encephalocele. PMID- 26862453 TI - Apoplexy in an intradural clival chordoma causing intraventricular bleed. AB - BACKGROUND: A few cases depicting apoplexy in a chordoma have been reported. Rarely, this intratumoral bleed may spillover into intracerebral or intraventricular regions. CASE DESCRIPTION: The authors report an intradural variety of clival chordoma presenting with apoplexy and spillover of blood into lateral ventricle. Clinical presentation, radiological scans, and relevant literature is also described. CONCLUSIONS: In a stable case of clival chordoma, intratumoral bleed or apoplexy may cause rapid neurological worsening and warranting urgent surgical intervention. PMID- 26862454 TI - Delayed chronic intracranial subdural hematoma complicating resection of a tanycytic thoracic ependymoma. AB - BACKGROUND: To demonstrate that the diagnosis of an intracranial subdural hematoma should be considered for patients presenting with acute or delayed symptoms of intracranial pathology following resection of a spinal tumor. CASE DESCRIPTION: We present a case of a 57-year-old woman found to have a chronic subdural hematoma 1 month following resection of a thoracic extramedullary ependymoma. Evacuation of the hematoma through a burr hole relieved the presenting symptoms and signs. Resolution of the hematoma was confirmed with a computed tomography (CT) scan. CONCLUSION: Headache and other symptoms not referable to spinal pathology should be regarded as a warning sign of an intracranial subdural hematoma, and a CT scan of the head should be obtained. The mechanism of the development of the hematoma may be related to the leakage of cerebrospinal fluid with subsequent intracranial hypotension leading to an expanding subdural space and hemorrhage. PMID- 26862455 TI - Alopecia due to an allergic reaction to metal head-pins used in a neurosurgical operation. AB - BACKGROUND: Allergic reactions to the metal head-pins of a head fixation holder are rare. CASE DESCRIPTION: A 45-year-old woman was referred to our hospital for the treatment of unruptured cerebral aneurysms. She underwent successful surgical treatment using four head-pins of the Sugita frame. At her first outpatient visit 3 weeks after discharge, redness, sores, and focal hair loss were noted at all four areas where the pinning had been performed. The pin fixation was considered to be responsible for the alopecia because the condition of the scalp lesions was even in all four parts. Six months later, the scalp regained hair. The head-pins were made of stainless steel, containing iron, nickel, chromium, and other components. A previous history of contact dermatitis to metal jewellery was later proven. CONCLUSION: The history of metal allergy should have been carefully elicited because head fixation with head-pins is essential for neurosurgical procedures. PMID- 26862456 TI - Syringosubarachnoid shunting using a myringotomy tube. AB - BACKGROUND: Syringomyelia results from obstruction of cerebrospinal fluid (CSF) flow due to a multitude of causes. Often symptoms of pain, weakness, and sensory disturbance are progressive and require surgical treatment. We present here a rare technique for syringosubarachnoid shunting. CASE DESCRIPTION: We present the case of a 38-year-old male who suffered a traumatic cervical spinal cord injury due to a motor vehicle accident. With progressive pain and motor decline, a magnetic resonance imaging was obtained and showed a new syrinx extending cervical multiple segments. A unique surgical procedure using a myringotomy tube to shunt CSF into the subarachnoid space was employed in this case. The patient's examination stabilized postoperatively, and at 2 months and 6 months follow-up visits, his strength and sensation continued to improve. CONCLUSION: We used a myringotomy tube for syringosubarachnoid shunting for the surgical management of a posttraumatic syrinx with good results. This technique minimizes suturing and may minimize shunt-related complications. PMID- 26862457 TI - Ruptured pseudoaneurysm of the middle meningeal artery presenting with a temporal lobe hematoma and a contralateral subdural hematoma. AB - BACKGROUND: Traumatic pseudoaneurysms of the middle meningeal artery (MMA) are rare, associated with skull fractures, and have a high mortality rate. When they rupture, MMA pseudoaneurysms frequently cause epidural hematomas and occasionally ipsilateral subdural or subarachnoid hemorrhage. Isolated intraparenchymal hemorrhage has also been reported. CASE DESCRIPTION: A 54-year-old female who suffered a loss of consciousness resulting in a fall presented with a Glasgow Coma Scale of 7t. Imaging demonstrated a right subdural hematoma (SDH) with midline shift, left skull fracture overlying the left MMA, and left temporal lobe intraparenchymal hematoma extending to the surface. The patient underwent a right craniectomy with evacuation of the SDH, and the preoperative computed tomographic angiography revealed abnormal dilation of the left MMA consistent with a pseudoaneurysm. The pseudoaneurysm was treated with endovascular treatment, and the intraparenchymal hematoma was treated conservatively. Her recovery was uneventful, and she received a cranioplasty 3 months after the decompression. CONCLUSIONS: The presence of a fracture over the MMA and intraparenchymal hematoma should prompt suspicion for a traumatic pseudoaneurysm. Pseudoaneurysms of the MMA can cause catastrophic bleeding, and prompt treatment is necessary. Endovascular embolization is an effective method that decreases the hemorrhage risk of MMA pseudoaneurysms. PMID- 26862458 TI - Microvascular decompression for glossopharyngeal neuralgia using intraoperative neurophysiological monitoring: Technical case report. AB - BACKGROUND: Glossopharyngeal neuralgia (GN) is a rare functional disorder representing around 1% of cases of trigeminal neuralgia. Lancinating throat and ear pain while swallowing are the typical manifestations, and are initially treated using anticonvulsants such as carbamazepine. Medically refractory GN is treated surgically. Microvascular decompression (MVD) is reportedly effective against GN, superseding rhizotomy and tractotomy. METHODS: We encountered three patients with medically refractory GN who underwent MVD using intraoperative neurophysiological monitoring (IONM). The offending vessels were the posterior inferior cerebellar arteries, which were confirmed intraoperatively via a transcondylar fossa approach to be affecting the root exit zones of the glossopharyngeal and vagus nerves. As IONM, facial motor-evoked potentials (MEPs) and brainstem auditory-evoked potentials were monitored during microsurgery in all three patients. Pharyngeal and vagal MEPs were added for two patients to avoid postoperative dysphagia. RESULTS: GN disappeared immediately after surgery with complete preservation of hearing acuity and facial nerve function. Transient mild swallowing disturbance was observed in 1 patient without pharyngeal or vagal MEPs, whereas the remaining two patients with pharyngeal and vagal MEPs demonstrated no postoperative dysphagia. CONCLUSION: Although control of severe pain is expected in surgical intervention for GN, lower cranial nerves are easily damaged because of their fragility, even in MVD. IONM including pharyngeal and vagal MEPs appears very useful for avoiding postoperative sequelae during MVD for GN. PMID- 26862460 TI - Timing of retreatment for patients with previously coiled or clipped intracranial aneurysms: Analysis of 156 patients with multiple treatments. AB - BACKGROUND: Some patients require a second surgical intervention for recurrence of treated aneurysms, untreated aneurysms in patients with multiple lesions, or de novo aneurysm. This retrospective review of the data was undertaken to evaluate when retreatment is necessary after initial aneurysm treatment. METHODS: Cerebral aneurysms in 1755 patients were treated via clipping or coiling between January 1995 and September 2012. Postoperative follow-up was performed at 6 months after treatment and was repeated every 12 months (or longer) after treatment using three-dimensional computed tomography angiography or magnetic resonance angiography. RESULTS: A cumulative total of 156 patients (8.9%) (117 women, 39 men; mean age: 55.0 years; range: 25-79 years) needed retreatment for rupture or regrowth of aneurysm (n = 31; ruptured (R)/remaining unruptured (U), 26/5), formation of de novo aneurysm (n = 45; R/U, 23/22), known untreated aneurysm in patients with multiple lesions (n = 78; R/U, 5/73), and hemorrhage from undetected aneurysm (n = 2). The regrowth risk is higher after endovascular treatment than after craniotomy and clipping. Median time to retreatment was 187 months (range: 11-280 months) for regrowth, 165 months (range: 22-330 months) for de novo, and 24 months (range: 2.8-417 months) for known untreated aneurysm. Regrowth or known with subarachnoid hemorrhage were frequently treated within 2 years from initial treatment. CONCLUSIONS: Aneurysms with residua or untreated aneurysms in patients with multiple lesions carry a risk of bleeding during a relatively short period, whereas there is a small but significant risk of de novo formation and subsequent hemorrhage at over 10 years after previous treatment. PMID- 26862459 TI - Intraoperative indocyanine green videoangiography to guide decision making regarding need for vessel bypass: A case report and technical note. AB - BACKGROUND: Indocyanine green (ICG) videoangiography is an intraoperative technique recently used in vascular neurosurgery to assess the presence or absence of blood flow during critical times of a procedure. These include, but are not limited to, detecting whether daughter branches or perforators are patent after placing a vascular clip or determining whether an aneurysm has been completely isolated from the cerebral circulation after clipping. We present a case of a less-commonly reported application of ICG videoangiography involving the selection of a vessel to act as the bypass recipient once the need is identified during the surgical treatment of a complex intracranial aneurysm. CASE DESCRIPTION: A 51-year-old male presented with a ruptured dissecting superior cerebellar artery (SCA) aneurysm that had two branches arising from the dome. Due to the difficult morphology of this aneurysm, a superficial temporal artery to SCA bypass was planned. We used ICG videoangiography to identify the branch that had insufficient retrograde flow via collateral circulation, to which the bypass was performed, followed by the isolation of the aneurysm from the cerebral circulation using permanent surgical clips. CONCLUSION: Our case represents a possible use of ICG videoangiography during the operative treatment of a difficult aneurysm. Our patient suffered no infarcts postoperatively. In the correct clinical context, this method represents a possible treatment option for complex aneurysms requiring a bypass. PMID- 26862461 TI - Resection of a recurrent cervical internal carotid artery pseudoaneurysm after failed endovascular therapy. AB - BACKGROUND: Recurrence of a cervical internal carotid artery (ICA) pseudoaneurysm initially treated by endovascular means is rare. We report an instance where a patient returned with a recurrent, enlarging cervical ICA pseudoaneursym, 15 years after initial complete, endovascular occlusion of the ICA. CASE DESCRIPTION: Patient is a 64-year-old male with a history of a right cervical ICA pseudoaneurysm diagnosed 15 years ago after a car accident. At the time, he received endovascular occlusion of his right ICA. Recent serial imaging demonstrated progressive enlargement of his pseudoaneurysm, up to 6 cm * 5 cm * 5.5 cm, without evidence of internal flow or extravasation. Due to dysphagia and hoarseness, resection of the pseudoaneurysm was recommended. Dissection occurred down to the lesion, where its borders were skeletonized. Its stump at the proximal ICA was mobilized and clamped; the lesion was incised and the existing thrombus, as well as the coil mass, was removed. The distal ICA appeared completely scarred with no retrograde filling. There were branches from the external carotid artery that appeared to supply the pseudoaneurysm. The scarred remnant of the distal ICA was sutured and the stump at the proximal ICA was ligated. Once hemostasis was obtained, closure occurred via anatomical layers. Postoperatively, the patient woke up well; at discharge, he exhibited no respiratory distress or dysphagia. At 5 months follow-up, a computed tomography angiography of the neck revealed no evidence for a residual pseudoaneurysm. He continues on lifelong aspirin. CONCLUSION: Recurrence of a cervical ICA pseudoaneursym is rare. We caution that such a clinical scenario is possible, even 15 years after endovascular occlusion of the ICA. Branches from the external carotid artery may feed the pseudoaneursym and cause recurrence. This mechanism has not been reported. Perhaps longer clinical follow-up is necessary, especially if endovascular therapy is the initial treatment option. PMID- 26862462 TI - Type I and II Diabetic Adipose-Derived Stem Cells Respond In Vitro to Dehydrated Human Amnion/Chorion Membrane Allograft Treatment by Increasing Proliferation, Migration, and Altering Cytokine Secretion. AB - Objective: Human amniotic membranes have been shown to be effective for healing diabetic foot ulcers clinically and to regulate stem cell activity in vitro and in vivo; however, diabetic stem cells may be impaired as a sequela of the disease. In this study, dehydrated human amnion/chorion membrane (dHACM) allografts (EpiFix(r); MiMedx Group) were evaluated for their ability to regulate diabetic stem cells in vitro. Approach: Human adipose-derived stem cells (ADSCs) from normal, type I diabetic, and type II diabetic donors were treated with soluble extracts of dHACM and evaluated for proliferation after 3 days by DNA assay, chemotactic migration after 1 day by transwell assay, cytokine secretion after 3 days by multiplex ELISA, and gene expression after 5 days by reverse transcription-polymerase chain reaction. Results: Although diabetic ADSCs demonstrated decreased responses compared to normal ADSCs, dHACM treatment stimulated diabetic ADSCs to proliferate after 3 days and enhanced migration over 24 h, similar to normal ADSCs. dHACM-treated diabetic ADSCs modulated secretion of soluble signals, including regulators of inflammation, angiogenesis, and healing. All ADSCs evaluated also responded to dHACM treatment with altered expression of immunomodulatory genes, including interleukins (IL)-1alpha, IL 1beta, and IL-1RA. Innovation: This is the first reported case demonstrating that diabetic ADSCs respond to novel amniotic membrane therapies, specifically treatment with dHACM. Conclusion: dHACM stimulated diabetic ADSCs to migrate, proliferate, and alter cytokine expression suggesting that, despite their diabetic origin, ADSCs may respond to dHACM to accelerate diabetic wound healing. PMID- 26862463 TI - Comparative Study of Morphometric and Fourier Transform Infrared Spectroscopy Analyses of the Collagen Fibers in the Repair Process of Cutaneous Lesions. AB - Objective: Compare the efficacy of light-emitting diode (LED) and therapeutic ultrasound (TUS), combined with a semipermeable dressing (D), at forming collagen in skin lesions by morphometry and Fourier transform infrared spectroscopy (FT IR). Materials and Methods: Surgical skin wounds (2.5 cm) were created on 84 male Wistar rats divided into four groups (n=21): Group I (Control), Group II (LED), Group III (LED+D), and Group IV (US+D). On days 7, 14, and 21, the tissue samples were removed and divided into two pieces, one was used for histological examination (collagen) and the other for FT-IR. Results: The histomorphometric analysis showed no significant differences among groups for collagen deposition at 7 days. However, at 14 days, more deposition of collagen was noted in the groups LED (p<0.05) and LED+D (p<0.001) than in the control. At 21 days, the groups LED, LED+D, and US+D presented significantly greater deposition of collagen when compared with the control. The FT-IR spectra, at 14 days, LED+D had greater amounts of type I collagen, a better organization of fibers, and greater difference of mean separation between the groups, not observed at 7 and 21 days. Innovation: The histomorphometric and FT-IR analyses suggest that the association of semipermeable dressing to LED therapy and to TUS modulates biological events, increasing fibroblast/collagen response and accelerating dermal maturation. Conclusion: The histomorphometric and FT-IR analyses showed that LED therapy is more efficacious than TUS, when combined with a semipermeable dressing, and induced the collagen production in skin lesions. PMID- 26862464 TI - The Innate Immune System in Acute and Chronic Wounds. AB - Significance: This review article provides an overview of the critical roles of the innate immune system to wound healing. It explores aspects of dysregulation of individual innate immune elements known to compromise wound repair and promote nonhealing wounds. Understanding the key mechanisms whereby wound healing fails will provide seed concepts for the development of new therapeutic approaches. Recent Advances: Our understanding of the complex interactions of the innate immune system in wound healing has significantly improved, particularly in our understanding of the role of antimicrobials and peptides and the nature of the switch from inflammatory to reparative processes. This takes place against an emerging understanding of the relationship between human cells and commensal bacteria in the skin. Critical Issues: It is well established and accepted that early local inflammatory mediators in the wound bed function as an immunological vehicle to facilitate immune cell infiltration and microbial clearance upon injury to the skin barrier. Both impaired and excessive innate immune responses can promote nonhealing wounds. It appears that the switch from the inflammatory to the proliferative phase is tightly regulated and mediated, at least in part, by a change in macrophages. Defining the factors that initiate the switch in such macrophage phenotypes and functions is the subject of multiple investigations. Future Directions: The review highlights processes that may be useful targets for further investigation, particularly the switch from M1 to M2 macrophages that appears to be critical as dysregulation of this switch occurs during defective wound healing. PMID- 26862466 TI - Deregulated expression of the HSP40 family members Auxilin-1 and -2 is indicative of proteostasis imbalance and predicts patient outcome in Ph(+) leukemia. AB - BACKGROUND: Proteostasis is defined by the orchestrated control of anabolic and catabolic protein pathways. Disruption of proteostasis results in cell stress and adaptation to proteostasis imbalance is mediated by adaptive pathways such as the Heat Shock Response (including heat-shock proteins) or the unfolded protein response (UPR). The BCR-ABL1 kinase (Philadelphia chromosome) is the hallmark of chronic myeloid leukemia (CML) and defines a historically poor subset in acute lymphoblastic leukemia (Ph(+) ALL). We previously demonstrated the importance of the UPR and particularly of the IRE1/XBP1 signaling axis in Ph(+) ALL, while others demonstrated the therapeutic relevance of HSP70 in ALL. In this regard, HSP70 is regulated by smaller HSP40 s, whose function is so far poorly characterized. RESULTS: Herein, we characterize the expression of HSP40 s in Ph(+) ALL and CML. We show that these genes are not regulated in a pan-class manner and identify a homologous gene pair, namely Auxilin-1 (DNAJC6) and Auxilin 2 (GAK) with a unique expression profile. Overexpression of Auxilin-2, the ubiquitously expressed homologue of Auxilin-1 correlated with superior clinical outcome in ALL and was tightly linked to both IRE1 RNase and BCR-ABL1 kinase activities. CONCLUSIONS: Our findings suggest that HSP40 gens are uniquely regulated and provide a rationale for further studies between BCR-ABL1/IRE1-based therapies in combination with HSP40 inhibitors, thus opening potentially novel therapeutic avenues. PMID- 26862465 TI - Challenges and Opportunities in Drug Delivery for Wound Healing. AB - Significance: Chronic wounds remain a significant public health problem. Alterations in normal physiological processes caused by aging or diabetes lead to impaired tissue repair and the development of chronic and nonhealing wounds. Understanding the unique features of the wound environment will be required to develop new therapeutics that impact these disabling conditions. New drug delivery systems (DDSs) may enhance current and future therapies for this challenging clinical problem. Recent Advances: Historically, physical barriers and biological degradation limited the efficacy of DDSs in wound healing. In aiming at improving and optimizing drug delivery, recent data suggest that combinations of delivery mechanisms, such as hydrogels, small molecules, RNA interference (RNAi), as well as growth factor and stem cell-based therapies (biologics), could offer exciting new opportunities for improving tissue repair. Critical Issues: The lack of effective therapeutic approaches to combat the significant disability associated with chronic wounds has become an area of increasing clinical concern. However, the unique challenges of the wound environment have limited the development of effective therapeutic options for clinical use. Future Directions: New platforms presented in this review may provide clinicians and scientists with an improved understanding of the alternatives for drug delivery in wound care, which may facilitate the development of new therapeutic approaches for patients. PMID- 26862467 TI - Lactobacillus rhamnosus GG Effect on Behavior of Zebrafish During Chronic Ethanol Exposure. AB - Ethanol is a widely consumed drug, which acts on the central nervous system to induce behavioral alterations ranging from disinhibition to sedation. Recent studies have produced accumulating evidence for the therapeutic role of probiotic bacteria in behavior. We aimed to investigate the effect of Lactobacillus rhamnosus GG (LGG) on the behavior of adult zebrafish chronically exposed to ethanol. Adult wild-type zebrafish were randomly divided into four groups, each containing 15 fish. The following groups were formed: Control (C), received unsupplemented feed during the trial period; Probiotic (P), fed with feed supplemented with LGG; Ethanol (E), received unsupplemented feed and 0.5% of ethanol directly added to the tank water; and Probiotic+Ethanol (P+E), group under ethanol exposure (0.5%) and fed with LGG supplemented feed. After 2 weeks of exposure, the novel tank test was used to evaluate fish behavior, which was analyzed using computer-aided video tracking. LGG alone did not alter swimming behavior of the fish. Ethanol exposure led to robust behavioral effects in the form of reduced anxiety levels, as indicated by increased vertical exploration and more time spent in the upper region of the novel tank. The group exposed to ethanol and treated with LGG behaved similarly to animals exposed to ethanol alone. Taken together, these results show that zebrafish behavior was not altered by LGG per se, as seen in murine models. This was the first study to investigate the effects of a probiotic diet on behavior after a chronic ethanol exposure. PMID- 26862468 TI - The Effect of Biomaterials Used for Tissue Regeneration Purposes on Polarization of Macrophages. AB - Activation of macrophages is critical in the acute phase of wound healing after implantation of surgical biomaterials. To understand the response of macrophages, they are often cultured in vitro on biomaterials. Since a wide range of biomaterials is currently used in the clinics, we undertook a systematic review of the macrophage polarization in response to these different surgical biomaterials in vitro. Beside the chemistry, material characteristics such as dimension, pore size, and surface topography are of great influence on the response of macrophages. The macrophage response also appears to depend on the differences in sterilization techniques that induce lasting biochemical changes or residues of chemicals and their byproducts used for sterilization. Regarding tissue-based biomaterials, macrophages on human or porcine dermis, strongly cross linked by chemicals elicit in general a proinflammatory response with higher amounts of proinflammatory cytokines. Synthetic biomaterials such as polyethylene, polyethylene terephthalate (PET) + polyacrylamide (PAAm), PET + sodium salt of poly(acrylic acid) (PAANa), perfluoropolyether (PFPE) with large posts, PEG-g-PA, and polydioxanone (PDO) always appear to elicit an anti inflammatory response in macrophages, irrespective of origin of the macrophages, for example, buffy coats or full blood. In conclusion, in general in vitro models contribute to evaluate the foreign body reaction on surgical biomaterials. Although it is difficult to simulate complexity of host response elicited by biomaterials, after their surgical implantation, an in vitro model gives indications of the initial foreign body response and allows the comparison of this response between biomaterials. PMID- 26862469 TI - A Pilot Study of Raltegravir Plus Combination Antiretroviral Therapy in Early Human Immunodeficiency Virus Infection: Challenges and Lessons Learned. AB - Availability of integrase strand transfer inhibitors created interest in determining whether their use would decrease persistently infected cell numbers. This study hypothesized that adding raltegravir (RAL) to standard antiretroviral therapy (ART) would decrease human immunodeficiency virus (HIV)-infected CD4(+) T cells more than standard combination ART. This was a pilot, randomized study comparing open-label standard triple ART to standard triple ART plus RAL over 96 weeks in ART-naive adults with early HIV infection. The primary objective was to compare quantity and trajectory of HIV DNA. Eighty-two persons were referred. A diverse set of reasons precluded the enrollment of all but 10. Those who enrolled and completed the study had an estimated median duration of HIV infection of 74 days at ART start. The groups had similar baseline characteristics. The RAL group had more rapid first phase plasma HIV RNA decay (0.67 log10 copies/mL/day) than with combination ART (0.34 log10copies/mL/day), p = 0.037. Second phase HIV RNA decay, residual viremia, cell-associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circle levels did not differ between groups. Among those with entry plasma HIV RNA levels above the median, 2LTR circles were significantly lower over time than in those with lower entry HIV RNA levels (p = 0.02). Our results suggest homogeneity of responses in cell associated RNA, HIV DNA, CD4(+) T-cells with replication-competent virus, and 2LTR circles with early HIV in both ART groups. The kinetics of 2LTR DNA did not reflect the kinetics of plasma HIV RNA decline following ART initiation. PMID- 26862470 TI - Allogeneic Transplantation of Periodontal Ligament-Derived Multipotent Mesenchymal Stromal Cell Sheets in Canine Critical-Size Supra-Alveolar Periodontal Defect Model. AB - Periodontitis is a chronic inflammatory disease that induces the destruction of tooth-supporting tissues, followed by tooth loss. Although several approaches have been applied to periodontal regeneration, complete periodontal regeneration has not been accomplished. Tissue engineering using a combination of cells and scaffolds is considered to be a viable alternative strategy. We have shown that autologous transplantation of periodontal ligament-derived multipotent mesenchymal stromal cell (PDL-MSC) sheets regenerates periodontal tissue in canine models. However, the indications for autologous cell transplantation in clinical situations are limited. Therefore, this study evaluated the safety and efficacy of allogeneic transplantation of PDL-MSC sheets using a canine horizontal periodontal defect model. Canine PDL-MSCs were labeled with enhanced green fluorescent protein (EGFP) and were cultured on temperature-responsive dishes. Three-layered cell sheets were transplanted around denuded root surfaces either autologously or allogeneically. A mixture of beta-tricalcium phosphate and collagen gel was placed on the bone defects. Eight weeks after transplantation, dogs were euthanized and subjected to microcomputed tomography and histological analyses. RNA and DNA were extracted from the paraffin sections to verify the presence of EGFP at the transplantation site. Inflammatory markers from peripheral blood sera were quantified using an enzyme-linked immunosorbent assay. Periodontal regeneration was observed in both the autologous and the allogeneic transplantation groups. The allogeneic transplantation group showed particularly significant regeneration of newly formed cementum, which is critical for the periodontal regeneration. Serum levels of inflammatory markers from peripheral blood sera showed little difference between the autologous and allogeneic groups. EGFP amplicons were detectable in the paraffin sections of the allogeneic group. These results suggest that allogeneic PDL-MSC sheets promoted periodontal tissue regeneration without side effects. Therefore, allogeneic transplantation of PDL MSC sheets has a potential to become an alternative strategy for periodontal regeneration. PMID- 26862471 TI - Heterogeneous Differentiation of Human Mesenchymal Stem Cells in 3D Extracellular Matrix Composites. AB - Extracellular matrix (ECM) proteins are structural elements of tissue and also potent signaling molecules. Previously, our laboratory showed that ECM of 2D coatings can trigger differentiation of bone marrow-derived mesenchymal stem cells (MSCs) into mesodermal lineages in an ECM-specific manner over 14 days, in some cases comparable to chemical induction. To test whether a similar effect was possible in a 3D, tissue-like environment, we designed a synthetic-natural biomaterial composite. The composite can present whole-molecule ECM proteins to cells, even those that do not spontaneously form hydrogels ex vivo, in 3D. To this end, we entrapped collagen type I, laminin-111, or fibronectin in ECM composites with MSCs and directly compared markers of mesodermal differentiation including cardiomyogenic (ACTC1), osteogenic (SPP1), adipogenic (PPARG), and chondrogenic (SOX9) in 2D versus 3D. We found the 3D condition largely mimicked the 2D condition such that the addition of type I collagen was the most potent inducer of differentiation to all lineages tested. One notable difference between 2D and 3D was pronounced adipogenic differentiation in 3D especially in the presence of exogenous collagen type I. In particular, PPARG gene expression was significantly increased ~16-fold relative to chemical induction, in 3D and not in 2D. Unexpectedly, 3D engagement of ECM proteins also altered immunomodulatory function of MSCs in that expression of IL-6 gene was elevated relative to basal levels in 2D. In fact, levels of IL-6 gene expression in 3D composites containing exogenously supplied collagen type I or fibronectin were statistically similar to levels attained in 2D with tumor necrosis factor-alpha (TNF-alpha) stimulation and these levels were sustained over a 2-week period. Thus, this novel biomaterial platform allowed us to compare the biochemical impact of whole molecule ECM proteins in 2D versus 3D indicating enhanced adipogenic differentiation and IL-6 expression of MSC in the 3D context. Exploiting the biochemical impact of ECM proteins on MSC differentiation and immunomodulation could augment the therapeutic utility of MSCs. PMID- 26862475 TI - Gastrointestinal granuloma due to Candida albicans in an immunocompetent cat. AB - A 3.5 year-old cat was admitted to the University of Melbourne Veterinary Teaching Hospital for chronic vomiting. Abdominal ultrasonography revealed a focal, circumferential thickening of the wall of the duodenum extending from the pylorus aborally for 3 cm, and an enlarged gastric lymph node. Cytology of fine needle aspirates of the intestinal mass and lymph node revealed an eosinophilic inflammatory infiltrate and numerous extracellular septate acute angle branching fungal-type hyphae. Occasional hyphae had globose terminal ends, as well as round to oval blastospores and germ tubes. Candida albicans was cultured from a surgical biopsy of the duodenal mass. No underlying host immunodeficiencies were identified. Passage of an abrasive intestinal foreign body was suspected to have caused intestinal mucosal damage resulting in focal intestinal candidiasis. The cat was treated with a short course of oral itraconazole and all clinical signs resolved. PMID- 26862473 TI - Targeting the Plasmodium vivax equilibrative nucleoside transporter 1 (PvENT1) for antimalarial drug development. AB - Infection with Plasmodium falciparum and vivax cause most cases of malaria. Emerging resistance to current antimalarial medications makes new drug development imperative. Ideally a new antimalarial drug should treat both falciparum and vivax malaria. Because malaria parasites are purine auxotrophic, they rely on purines imported from the host erythrocyte via Equilibrative Nucleoside Transporters (ENTs). Thus, the purine import transporters represent a potential target for antimalarial drug development. For falciparum parasites the primary purine transporter is the P. falciparum Equilibrative Nucleoside Transporter Type 1 (PfENT1). Recently we identified potent PfENT1 inhibitors with nanomolar IC50 values using a robust, yeast-based high throughput screening assay. In the current work we characterized the Plasmodium vivax ENT1 (PvENT1) homologue and its sensitivity to the PfENT1 inhibitors. We expressed a yeast codon-optimized PvENT1 gene in Saccharomyces cerevisiae. PvENT1-expressing yeast imported both purines ([(3)H]adenosine) and pyrimidines ([(3)H]uridine), whereas wild type (fui1Delta) yeast did not. Based on radiolabel substrate uptake inhibition experiments, inosine had the lowest IC50 (3.8 MUM), compared to guanosine (14.9 MUM) and adenosine (142 MUM). For pyrimidines, thymidine had an IC50 of 183 MUM (vs. cytidine and uridine; mM range). IC50 values were higher for nucleobases compared to the corresponding nucleosides; hypoxanthine had a 25-fold higher IC50 than inosine. The archetypal human ENT1 inhibitor 4 nitrobenzylthioinosine (NBMPR) had no effect on PvENT1, whereas dipyridamole inhibited PvENT1, albeit with a 40 MUM IC50, a 1000-fold less sensitive than human ENT1 (hENT1). The PfENT1 inhibitors blocked transport activity of PvENT1 and the five known naturally occurring non-synonymous single nucleotide polymorphisms (SNPs) with similar IC50 values. Thus, the PfENT1 inhibitors also target PvENT1. This implies that development of novel antimalarial drugs that target both falciparum and vivax ENT1 may be feasible. PMID- 26862472 TI - Special Morphological Features at the Interface of the Renal Stem/Progenitor Cell Niche Force to Reinvestigate Transport of Morphogens During Nephron Induction. AB - Formation of a nephron depends on reciprocal signaling of different morphogens between epithelial and mesenchymal cells within the renal stem/progenitor cell niche. Previously, it has been surmised that a close proximity exists between both involved cell types and that morphogens are transported between them by diffusion. However, actual morphological data illustrate that mesenchymal and epithelial stem/progenitor cell bodies are separated by a striking interface. Special fixation of specimens by glutaraldehyde (GA) solution including cupromeronic blue, ruthenium red, or tannic acid for electron microscopy depicts that the interface is not void but filled in extended areas by textured extracellular matrix. Surprisingly, projections of mesenchymal cells cross the interface to contact epithelial cells. At those sites the plasma membranes of a mesenchymal and an epithelial cell are connected via tunneling nanotubes. Regarding detected morphological features in combination with involved morphogens, their transport cannot longer be explained solely by diffusion. Instead, it has to be sorted according to biophysical properties of morphogens and to detected environment. Thus, the new working hypothesis is that morphogens with good solubility such as glial cell line-derived neurotrophic factor (GDNF) or fibroblast growth factors (FGFs) are transported by diffusion. Morphogens with minor solubility such as bone morphogenetic proteins (BMPs) are secreted and stored for delivery on demand in illustrated extracellular matrix. In contrast, morphogens with poor solubility such as Wnts are transported in mesenchymal cell projections along the plasma membrane or via illustrated tunneling nanotubes. However, the presence of an intercellular route between mesenchymal and epithelial stem/progenitor cells by tunneling nanotubes also makes it possible that all morphogens are transported this way. PMID- 26862474 TI - Low-dose benznidazole treatment results in parasite clearance and attenuates heart inflammatory reaction in an experimental model of infection with a highly virulent Trypanosoma cruzi strain. AB - Chagas disease, caused by Trypanosoma cruzi, is the main cause of dilated cardiomyopathy in the Americas. Antiparasitic treatment mostly relies on benznidazole (Bzl) due to Nifurtimox shortage or unavailability. Both induce adverse drug effects (ADE) of varied severity in many patients, leading to treatment discontinuation or abandonment. Since dosage may influence ADE, we aimed to assess Bzl efficacy in terms of parasiticidal and anti-inflammatory activity, using doses lower than those previously reported. BALB/c mice infected with the T. cruzi RA strain were treated with different doses of Bzl. Parasitaemia, mortality and weight change were assessed. Parasite load, tissue infiltrates and inflammatory mediators were studied in the heart. Serum creatine kinase (CK) activity was determined as a marker of heart damage. The infection independent anti-inflammatory properties of Bzl were studied in an in vitro model of LPS-treated cardiomyocyte culture. Treatment with 25 mg/kg/day Bzl turned negative the parasitological parameters, induced a significant decrease in IL 1beta, IL-6 and NOS2 in the heart and CK activity in serum, to normal levels. No mortality was observed in infected treated mice. Primary cultured cardiomyocytes treated with Bzl showed that inflammatory mediators were reduced via inhibition of the NF-kappaB pathway. A Bzl dose lower than that previously reported for treatment of experimental Chagas disease exerts adequate antiparasitic and anti inflammatory effects leading to parasite clearance and tissue healing. This may be relevant to reassess the dose currently used for the treatment of human Chagas disease, aiming to minimize ADE. PMID- 26862476 TI - Ventriculitis due to infection with Rhizopus arrhizus. AB - A 52-year-old heart-lung transplant patient presented to the emergency department with acute onset of neurologic symptoms. MRI showed ballooning of the left ventricle, midline shift and contrast enhancement in the anterior horn of the left ventricle. Ventricle neuroendoscopy revealed whitish, floccose aerial structures within the left ventricle. Brain biopsy cultures grew Rhizopus arrhizus. Therapy with liposomale amphotericin B and posaconazole was performed. Except for hemianopsia and deficits in minute motor activity, the patient completely recovered. PMID- 26862477 TI - Language comprehension and brain function in individuals with an optimal outcome from autism. AB - Although Autism Spectrum Disorder (ASD) is generally a lifelong disability, a minority of individuals with ASD overcome their symptoms to such a degree that they are generally indistinguishable from their typically-developing peers. That is, they have achieved an Optimal Outcome (OO). The question addressed by the current study is whether this normalized behavior reflects normalized brain functioning, or alternatively, the action of compensatory systems. Either possibility is plausible, as most participants with OO received years of intensive therapy that could alter brain networks to align with typical function or work around ASD-related neural dysfunction. Individuals ages 8 to 21 years with high-functioning ASD (n = 23), OO (n = 16), or typical development (TD; n = 20) completed a functional MRI scan while performing a sentence comprehension task. Results indicated similar activations in frontal and temporal regions (left middle frontal, left supramarginal, and right superior temporal gyri) and posterior cingulate in OO and ASD groups, where both differed from the TD group. Furthermore, the OO group showed heightened "compensatory" activation in numerous left- and right-lateralized regions (left precentral/postcentral gyri, right precentral gyrus, left inferior parietal lobule, right supramarginal gyrus, left superior temporal/parahippocampal gyrus, left middle occipital gyrus) and cerebellum, relative to both ASD and TD groups. Behaviorally normalized language abilities in OO individuals appear to utilize atypical brain networks, with increased recruitment of language-specific as well as right homologue and other systems. Early intensive learning and experience may normalize behavioral language performance in OO, but some brain regions involved in language processing may continue to display characteristics that are more similar to ASD than typical development, while others show characteristics not like ASD or typical development. PMID- 26862479 TI - Tumor necrosis factor-alpha (- 308G/A, + 488G/A, - 857C/T and -1031 T/C) gene polymorphisms and risk of ischemic stroke in north Indian population: A hospital based case-control study. AB - BACKGROUND: Genetic factors may play a role in the susceptibility of Ischemic stroke (IS). Previous studies have shown that Tumour necrosis factor-alpha (TNF alpha) gene polymorphisms were associated with the risk of IS in multiple ethnicities. The present case-control study tested the hypothesis that genetic polymorphisms of the TNF-alpha gene may affect the risk of IS in North Indian population. We investigated the association of four single nucleotide polymorphisms (- 308G/A, + 488G/A, - 857C/T and -1031 T/C) within TNF-alpha gene promoter and their haplotypes with the risk of IS. METHODS: IS was classified using the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification. Genotyping was performed for 250 IS patients and 250 age- and sex-matched IS free controls by using SNaPshot technique. Multivariate logistic regression was used to control the confounding effects of demographic and risk factor variables. Haplotype analyses were done by using PHASE software and Linkage disequilibrium (LD) analyses were done by using Haploview version 4.2 software. RESULTS: An independent association between TNF-alpha + 488G/A (OR = 2.59; 95%CI 1.46 to 4.60; p = 0.001) and -857C/T (OR = 1.77; 95%CI 1.01 to 3.11; p < 0.04) and risk of IS was observed under dominant model. However, no significant association between -308G/A and -1031 T/C gene polymorphisms and risk of IS was observed. Haplotype analysis showed that A308-G488-C857-T1031 haplotypes were significantly associated with the increased risk of IS [OR = 1.66; 95%CI 1.02 to 2.71; p = 0.003]. Strong linkage disequilibrium (LD) was observed for + 488G/A and -857C/T (D' = 0.41, r(2) = 0.004). CONCLUSIONS: Two SNPs (+ 488G/A and -857C/T) of TNF alpha gene and their haplotypes are significantly associated with the risk of IS in the population enrolled from North India. Our findings indicate that polymorphisms and haplotypes of TNF-alpha gene may be used as a genetic marker for identifying individuals at increased risk for developing IS. PMID- 26862480 TI - Common functional polymorphism within miR-146a and miR-196a-2 as susceptibility loci for hepatocellular carcinoma: An updated meta-analysis. AB - BACKGROUND: Mutations or single nucleotide polymorphisms (SNPs) within the gene region of microRNAs play an important role for the development of hepatocellular carcinoma (HCC). Extensive studies have tried to investigate the susceptibility role of miR-146a rs2819164 and miR-196a-2 rs11614913. However, these results are still inconsistent and inconclusive. We undertook a meta-analysis containing primarily Asian studies to assess the associations of the two SNPs with HCC risk. METHODS: 19 studies including miR-146a (7170 cases and 9443 controls) and 15 studies including miR-196a-2 (6417 cases and 7627 controls) were used for meta analysis. Odds ratios and 95% CI were calculated to assess the association in five different genetic models. RESULTS: For the rs2910164 polymorphism of miR 146a, significantly increased risks for HCC were observed when all studies were pooled under two models (CG vs CC: OR = 1.11, 95% CI = 1.02-1.21, P = 0.021; GG + CG vs CC: OR = 1.11, 95% CI = 1.01-1.22, P = 0.035). For the rs11614913 polymorphism of miR-196a-2, significant increased risks for HCC development were observed when all studies were pooled under four models (C vs T: OR = 1.14, 95% CI = 1.06-1.23, P = 0.001; CC vs TT: OR = 1.31, 95% CI = 1.12-1.53, P = 0.001; CC + TC vs TT: OR = 1.16, 95% CI = 1.03-1.31, P = 0.018; CC vs TC + TT: OR = 1.14, 95% CI = 1.00-1.30, P = 0.043). CONCLUSION: Our results show that the two common SNPs within the miRNAs were associated with modest increased risk of HCC (OR < 1.6), especially in the Asian population. Larger population-based studies validating these results are needed. PMID- 26862481 TI - Genetic diversity and molecular evolution of Naga King Chili inferred from internal transcribed spacer sequence of nuclear ribosomal DNA. AB - Sequences of the Internal Transcribed Spacer (ITS1-5.8S-ITS2) of nuclear ribosomal DNAs were explored to study the genetic diversity and molecular evolution of Naga King Chili. Our study indicated the occurrence of nucleotide polymorphism and haplotypic diversity in the ITS regions. The present study demonstrated that the variability of ITS1 with respect to nucleotide diversity and sequence polymorphism exceeded that of ITS2. Sequence analysis of 5.8S gene revealed a much conserved region in all the accessions of Naga King Chili. However, strong phylogenetic information of this species is the distinct 13 bp deletion in the 5.8S gene which discriminated Naga King Chili from the rest of the Capsicum sp. Neutrality test results implied a neutral variation, and population seems to be evolving at drift-mutation equilibrium and free from directed selection pressure. Furthermore, mismatch analysis showed multimodal curve indicating a demographic equilibrium. Phylogenetic relationships revealed by Median Joining Network (MJN) analysis denoted a clear discrimination of Naga King Chili from its closest sister species (Capsicum chinense and Capsicum frutescens). The absence of star-like network of haplotypes suggested an ancient population expansion of this chili. PMID- 26862478 TI - Translating state-of-the-art spinal cord MRI techniques to clinical use: A systematic review of clinical studies utilizing DTI, MT, MWF, MRS, and fMRI. AB - BACKGROUND: A recent meeting of international imaging experts sponsored by the International Spinal Research Trust (ISRT) and the Wings for Life Foundation identified 5 state-of-the-art MRI techniques with potential to transform the field of spinal cord imaging by elucidating elements of the microstructure and function: diffusion tensor imaging (DTI), magnetization transfer (MT), myelin water fraction (MWF), MR spectroscopy (MRS), and functional MRI (fMRI). However, the progress toward clinical translation of these techniques has not been established. METHODS: A systematic review of the English literature was conducted using MEDLINE, MEDLINE-in-Progress, Embase, and Cochrane databases to identify all human studies that investigated utility, in terms of diagnosis, correlation with disability, and prediction of outcomes, of these promising techniques in pathologies affecting the spinal cord. Data regarding study design, subject characteristics, MRI methods, clinical measures of impairment, and analysis techniques were extracted and tabulated to identify trends and commonalities. The studies were assessed for risk of bias, and the overall quality of evidence was assessed for each specific finding using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. RESULTS: A total of 6597 unique citations were identified in the database search, and after full-text review of 274 articles, a total of 104 relevant studies were identified for final inclusion (97% from the initial database search). Among these, 69 studies utilized DTI and 25 used MT, with both techniques showing an increased number of publications in recent years. The review also identified 1 MWF study, 11 MRS studies, and 8 fMRI studies. Most of the studies were exploratory in nature, lacking a priori hypotheses and showing a high (72%) or moderately high (20%) risk of bias, due to issues with study design, acquisition techniques, and analysis methods. The acquisitions for each technique varied widely across studies, rendering direct comparisons of metrics invalid. The DTI metric fractional anisotropy (FA) had the strongest evidence of utility, with moderate quality evidence for its use as a biomarker showing correlation with disability in several clinical pathologies, and a low level of evidence that it identifies tissue injury (in terms of group differences) compared with healthy controls. However, insufficient evidence exists to determine its utility as a sensitive and specific diagnostic test or as a tool to predict clinical outcomes. Very low quality evidence suggests that other metrics also show group differences compared with controls, including DTI metrics mean diffusivity (MD) and radial diffusivity (RD), the diffusional kurtosis imaging (DKI) metric mean kurtosis (MK), MT metrics MT ratio (MTR) and MT cerebrospinal fluid ratio (MTCSF), and the MRS metric of N-acetylaspartate (NAA) concentration, although these results were somewhat inconsistent. CONCLUSIONS: State-of-the-art spinal cord MRI techniques are emerging with great potential to improve the diagnosis and management of various spinal pathologies, but the current body of evidence has only showed limited clinical utility to date. Among these imaging tools DTI is the most mature, but further work is necessary to standardize and validate its use before it will be adopted in the clinical realm. Large, well-designed studies with a priori hypotheses, standardized acquisition methods, detailed clinical data collection, and robust automated analysis techniques are needed to fully demonstrate the potential of these rapidly evolving techniques. PMID- 26862482 TI - Clinical characteristics and follow-up of 5 young Chinese males with gonadotropin releasing hormone deficiency caused by mutations in the KAL1 gene. AB - Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) pertains to a group of genetic disorders consisting of anosmic hypogonadotropic hypogonadism (Kallmann syndrome, KS) and normosmic idiopathic hypogonadotropic hypogonadism (nIHH). KS is genetically heterogeneous. We hereby present 5 young male patients with GnRH deficiency caused by mutations in the KAL1 gene. Their ages ranged from 9 months to 16 years. They were referred to our department for an endocrine consultation for micropenis. Hormone assays showed low circulating gonadotropins and testosterone. Molecular studies revealed KAL1 mutations in all cases, three reported nonsense sequence variants in the KAL1 gene were detected in 4 patients, respectively (c.784C > T (p.Arg 262*), c.1267C > T (p.Arg423*), and c.1270C > T (p.Arg424*)), and one patient harbored a novel hemizygous sequence variant [c.227G > A (p.Trp76*)]. Only one patient presented short stature without growth hormone deficiency and anosmia. Another patient had bilateral eyelid ptosis, trichiasis, and refractive error. This is the first report on the co-occurrence of a KAL1 gene mutation and tent-like upper lip in four patients. All of our cases had normal olfactory bulbs and showed no renal agenesis, cleft lip/palate, and hearing impairment. These cases expand our knowledge of the phenotype associated with KAL1 sequence variations, although the precise mechanism by which KAL1 gene influences the development of this phenotype is still unknown. PMID- 26862483 TI - IsoSeq analysis and functional annotation of the infratentorial ependymoma tumor tissue on PacBio RSII platform. AB - Here, we sequenced and functionally annotated the long reads (1-2 kb) cDNAs library of an infratentorial ependymoma tumor tissue on PacBio RSII by Iso-Seq protocol using SMRT technology. 577 MB, data was generated from the brain tissues of ependymoma tumor patient, producing 1,19,313 high-quality reads assembled into 19,878 contigs using Celera assembler followed by Quiver pipelines, which produced 2952 unique protein accessions in the nr protein database and 307 KEGG pathways. Additionally, when we compared GO terms of second and third level with alternative splicing data obtained through HTA Array2.0. We identified four and twelve transcript cluster IDs in Level-2 and Level-3 scores respectively with alternative splicing index predicting mainly the major pathways of hallmarks of cancer. Out of these transcript cluster IDs only transcript cluster IDs of gene PNMT, SNN and LAMB1 showed Reads Per Kilobase of exon model per Million mapped reads (RPKM) values at gene-level expression (GE) and transcript-level (TE) track. Most importantly, brain-specific genes--PNMT, SNN and LAMB1 show their involvement in Ependymoma. PMID- 26862485 TI - Chromosomal microarray analysis, or comparative genomic hybridization: A high throughput approach. AB - Pathological copy number variants (CNVs) and point mutations are major genetic causes of hundreds of disorders. Comparative genomic hybridization (CGH) also known as chromosomal microarray analysis (CMA) is the best available tool to detect copy number variations in chromosomal make up. We have optimized several different protocols and introduce a high-throughput approach to perform a cost effective, fast, high-throughput and high-quality CMA. We managed to reach to high quality arrays with 17 +/- 0.04 (mean +/- SD, n = 90) Derivative Log Ratio (DLR) spread, a measure of array quality (<0.20 considered as excellent) for our arrays. High-throughput and high-quality arrays are gaining more attention and the current manuscript is a step forward to this increasing demand.*This manuscript introduces a low cost, fast, efficient, high throughput and high quality aCGH protocol;*This protocol provides specific instructions and crucial detail for processing up to 24 slides which is equal to 48, 96, or 192 arrays by only one person in one day;*This manuscript is accompanied with a step-by-step video. PMID- 26862484 TI - Polymorphisms of glutathione S-transferase and methylenetetrahydrofolate reductase genes in Moldavian patients with ulcerative colitis: Genotype-phenotype correlation. AB - BACKGROUND: Glutathione S-transferases (GSTM1, GSTT1, and GSTP1) and methylenetetrahydrofolate reductase (MTHFR) are important enzymes for protection against oxidative stress. In addition, MTHFR has an essential role in DNA synthesis, repair, and methylation. Their polymorphisms have been implicated in the pathogenesis of ulcerative colitis (UC). The aim of the present study was to investigate the role of selected polymorphisms in these genes in the development of UC in the Moldavian population. METHODS: In a case-control study including 128 UC patients and 136 healthy individuals, GSTM1 and GSTT1 genotypes (polymorphic deletions) were determined using multiplex polymerase chain reaction (PCR). The GSTP1 rs1695 (Ile105Val), MTHFR rs1801133 (C677T), and MTHFR rs1801131 (A1298C) polymorphisms were studied with restriction fragment length polymorphism (RFLP) analysis. Genotype-phenotype correlations were examined using logistic regression analysis. RESULTS: None of the genotypes, either alone or in combination, showed a strong association with UC. The case-only sub-phenotypic association analysis showed an association of the MTHFR rs1801133 polymorphism with the extent of UC under co-dominant (p corrected = 0.040) and recessive (p corrected = 0.020; OR = 0.15; CI = 0.04-0.63) genetic models. Also, an association between the MTHFR rs1801131 polymorphism and the severity of UC was reported for the over-dominant model (p corrected = 0.023; coefficient = 0.32; 95% CI = 0.10-0.54). CONCLUSION: The GST and MTHFR genotypes do not seem to be a relevant risk factor for UC in our sample. There was, however, evidence that variants in MTHFR may influence the clinical features in UC patients. Additional larger studies investigating the relationship between GST and MTHFR polymorphisms and UC are required. PMID- 26862486 TI - Neoadjuvant treatment for resectable pancreatic adenocarcinoma. AB - Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress. PMID- 26862487 TI - Current treatment options for patients with initially unresectable isolated colorectal liver metastases. AB - The development of liver metastases is a common clinical entity in the clinical course of colorectal cancer. For patients with isolated liver involvement, surgical resection is the only treatment that can provide a chance of prolonged survival and cure. However, most of these patients are not initially eligible for the surgery. Selected patients with initially considered to have unresectable disease may become resectable after systemic (chemotherapy +/- biological therapy) and loco-regional treatment modalities including hepatic arterial infusion. Patients who have colorectal liver metastases ideally should be referred to a multidisciplinary cancer care team in order to identify the most optimal management approach. PMID- 26862488 TI - Advanced oropharyngeal squamous cell carcinoma: Pathogenesis, treatment, and novel therapeutic approaches. AB - Oropharyngeal cancer accounts for approximately 2.8% of newly cancer cases. Although classically a tobacco related disease, most cases today are related to infection with human papilloma virus (HPV) and present with locally advanced tumors. HPV related tumors have been recognized as a molecularly distinct entity with higher response rates to therapy, lower rates of relapse, and improved overall survival. Treatment of oropharyngeal cancer entails a multi-disciplinary approach with concomitant chemoradiation. The role of induction chemotherapy in locally advanced tumors continues to be controversial however large studies have demonstrated no difference in survival or time to treatment failure. Surgical approaches may be employed with low volume oropharyngeal cancers and with development new endoscopic tools, more tumors are able to be resected via an endoscopic approach. Given advances in the understanding of HPV related oropharyngeal cancer, ongoing research is looking at ways to minimize toxicities via de-intensification of therapy. Unfortunately, some patients develop recurrent or metastatic disease. Novel therapeutics are currently being investigated for this patient population including immunotherapeutics. This review discusses the current understanding of the pathogenesis of oropharyngeal cancer and treatment. We also discuss emerging areas of research as it pertains to de-intensification as well novel therapeutics for the management of metastatic disease. PMID- 26862489 TI - Current therapeutic strategies for advanced pancreatic cancer: A review for clinicians. AB - Pancreatic cancer (PC) would become the second leading cause of cancer death in the near future, despite representing only 3% of new cancer diagnosis. Survival improvement will come from a better knowledge of risk factors, earlier diagnosis, better integration of locoregional and systemic therapies, as well as the development of more efficacious drugs rising from a deeper understanding of disease biology. For patients with unresectable, non-metastatic disease, combined strategies encompassing primary chemotherapy and radiation seems to be promising. In fit patients, new polychemotherapy regimens can lead to better outcomes in terms of slight but significant survival improvement associated with a positive impact on quality of life. The upfront use of these regimes can also increase the rate of radical resections in borderline resectable and locally advanced PC. Second line treatments showed to positively affect both overall survival and quality of life in fit patients affected by metastatic disease. At present, oxaliplatin-based regimens are the most extensively studied. Nonetheless, other promising drugs are currently under evaluation. Presently, in addition to surgery and conventional radiation therapy, new locoregional treatment techniques are emerging as alternative options in the multimodal approach to patients or diseases not suitable for radical surgery. As of today, in contrast with other types of cancer, targeted therapies failed to show relevant activity either alone or in combination with chemotherapy and, thus, current clinical practice does not include them. Up to now, despite the fact of extremely promising results in different tumors, also immunotherapy is not in the actual therapeutic armamentarium for PC. In the present paper, we provide a comprehensive review of the current state of the art of clinical practice and research in PC aiming to offer a guide for clinicians on the most relevant topics in the management of this disease. PMID- 26862490 TI - Current status of ultrasound-guided surgery in the treatment of breast cancer. AB - The primary goal of breast-conserving surgery (BCS) is to obtain tumour-free resection margins. Margins positive or focally positive for tumour cells are associated with a high risk of local recurrence, and in the case of tumour positive margins, re-excision or even mastectomy are sometimes needed to achieve definite clear margins. Unfortunately, tumour-involved margins and re-excisions after lumpectomy are still reported in up to 40% of patients and additionally, unnecessary large excision volumes are described. A secondary goal of BCS is the cosmetic outcome and one of the main determinants of worse cosmetic outcome is a large excision volume. Up to 30% of unsatisfied cosmetic outcome is reported. Therefore, the search for better surgical techniques to improve margin status, excision volume and consequently, cosmetic outcome has continued. Nowadays, the most commonly used localization methods for BCS of non-palpable breast cancers are wire-guided localization (WGL) and radio-guided localization (RGL). WGL and RGL are invasive procedures that need to be performed pre-operatively with technical and scheduling difficulties. For palpable breast cancer, tumour excision is usually guided by tactile skills of the surgeon performing "blind" surgery. One of the surgical techniques pursuing the aims of radicality and small excision volumes includes intra-operative ultrasound (IOUS). The best evidence available demonstrates benefits of IOUS with a significantly high proportion of negative margins compared with other localization techniques in palpable and non palpable breast cancer. Additionally, IOUS is non-invasive, easy to learn and can centralize the tumour in the excised specimen with low amount of healthy breast tissue being excised. This could lead to better cosmetic results of BCS. Despite the advantages of IOUS, only a small amount of surgeons are performing this technique. This review aims to highlight the position of ultrasound-guided surgery for malignant breast tumours in the search for better oncological and cosmetic outcomes. PMID- 26862493 TI - Intensive care outcomes in adult hematopoietic stem cell transplantation patients. AB - Although outcomes of intensive care for patients undergoing hematopoietic stem cell transplantation (HSCT) have improved in the last two decades, the short-term mortality still remains above 50% among allogeneic HSCT patients. Better selection of HSCT patients for intensive care, and consequently reduction of non beneficial care, may reduce financial costs and alleviate patient suffering. We reviewed the studies on intensive care outcomes of patients undergoing HSCT published since 2000. The risk factors for intensive care unit (ICU) admission identified in this report were primarily patient and transplant related: HSCT type (autologous vs allogeneic), conditioning intensity, HLA mismatch, and graft versus-host disease (GVHD). At the same time, most of the factors associated with ICU outcomes reported were related to the patients' functional status upon development of critical illness and interventions in ICU. Among the many possible interventions, the initiation of mechanical ventilation was the most consistently reported factor affecting ICU survival. As a consequence, our current ability to assess the benefit or futility of intensive care is limited. Until better ICU or hospital mortality prediction models are available, based on the available evidence, we recommend practitioners to base their ICU admission decisions on: Patient pre-transplant comorbidities, underlying disease status, GVHD diagnosis/grade, and patients' functional status at the time of critical illness. PMID- 26862492 TI - Overview, prevention and management of chemotherapy extravasation. AB - Chemotherapy extravasation remains an accidental complication of chemotherapy administration and may result in serious damage to patients. We review in this article the clinical aspects of chemotherapy extravasation and latest advances in definitions, classification, prevention, management and guidelines. We review the grading of extravasation and tissue damage according to various chemotherapeutic drugs and present an update on treatment and new antidotes including dexrazoxane for anthracyclines extravasation. We highlight the importance of education and training of the oncology team for prevention and prompt pharmacological and non pharmacological management and stress the availability of new antidotes like dexrazoxane wherever anthracyclines are being infused. PMID- 26862494 TI - Role of copper transporters in platinum resistance. AB - Platinum (Pt)-based antitumor agents are effective in the treatment of many solid malignancies. However, their efficacy is limited by toxicity and drug resistance. Reduced intracellular Pt accumulation has been consistently shown to correlate with resistance in tumors. Proteins involved in copper homeostasis have been identified as Pt transporters. In particular, copper transporter receptor 1 (CTR1), the major copper influx transporter, has been shown to play a significant role in Pt resistance. Clinical studies demonstrated that expression of CTR1 correlated with intratumoral Pt concentration and outcomes following Pt-based therapy. Other CTRs such as CTR2, ATP7A and ATP7B, may also play a role in Pt resistance. Recent clinical studies attempting to modulate CTR1 to overcome Pt resistance may provide novel strategies. This review discusses the role of CTR1 as a potential predictive biomarker of Pt sensitivity and a therapeutic target for overcoming Pt resistance. PMID- 26862495 TI - Recent advances in microvascular autologous breast reconstruction after ablative tumor surgery. AB - Breast cancer is a ubiquitous disease and one of the leading causes of death in women in western societies. With overall increasing survival rates, the number of patients who need post-mastectomy reconstruction is on the rise. Especially since its psychological benefits have been broadly recognized, breast reconstruction has become a key component of breast cancer treatment. Evolving from the early beginnings of breast reconstruction with synthetic implants in the 1960s, microsurgical tissue transfer is on the way to become the gold standard for post oncology restoration of the breast. Particularly since the advent of perforator based free flap surgery, free tissue transfer has become as safe option for breast reconstruction with low morbidity. The lower abdominal skin and subcutaneous fat tissue typically offer enough volume to create an aesthetically satisfying breast mound. Nowadays, the most commonly used flap from this donor site is the deep inferior epigastric artery perforator flap. If the lower abdomen is not available as a donor site, the gluteal area and thigh provide a number of flaps suitable for breast reconstruction. If the required breast volume is small, and there is enough tissue available on the upper medial thigh, then a transverse upper gracilis flap may be a practicable method to reconstruct the breast. In case of a higher amount of required volume, a gluteal artery perforator flap is the best choice. However, what is crucial in addition to selecting the best flap option for the individual patient is the timing of the operation. In patients with confirmed post-mastectomy radiation therapy, it is advisable to perform microvascular breast reconstruction only in a delayed fashion. PMID- 26862496 TI - Targeting metabolism in breast cancer: How far we can go? AB - Adjuvant therapies for breast cancer have achieved great success in recent years and early breast cancer is now a curable or chronic disease. Targeted therapies, including endocrine therapy and human epidermal growth factor receptor-2 targeted therapy, marked a new era of breast cancer treatment. However, except for chemotherapy, an efficient drug treatment to improve the overall survival of breast cancer patients is still lacking for triple negative breast cancer. Furthermore, a certain proportion of breast cancer patients present with resistance to drug therapy, making it much more difficult to control the deterioration of the disease. Recently, altered energy metabolism has become one of the hallmarks of cancer, including breast cancer, and it may be linked to drug resistance. Targeting cellular metabolism is becoming a promising strategy to overcome drug resistance in cancer therapy. This review discusses metabolic reprogramming in breast cancer and the possible complex mechanism of modulation. We also summarize the recent advances in metabolic therapy targeted glycolysis, glutaminolysis and fatty acids synthesis in breast cancer. PMID- 26862491 TI - Historical review of the causes of cancer. AB - In the early 1900s, numerous seminal publications reported that high rates of cancer occurred in certain occupations. During this period, work with infectious agents produced only meager results which seemed irrelevant to humans. Then in the 1980s ground breaking evidence began to emerge that a variety of viruses also cause cancer in humans. There is now sufficient evidence of carcinogenicity in humans for human T-cell lymphotrophic virus, human immunodeficiency virus, hepatitis B virus, hepatitis C virus, human papillomavirus, Epstein-Barr virus, and human herpes virus 8 according to the International Agency for Research on Cancer (IARC). Many other causes of cancer have also been identified by the IARC, which include: Sunlight, tobacco, pharmaceuticals, hormones, alcohol, parasites, fungi, bacteria, salted fish, wood dust, and herbs. The World Cancer Research Fund and the American Institute for Cancer Research have determined additional causes of cancer, which include beta carotene, red meat, processed meats, low fibre diets, not breast feeding, obesity, increased adult height and sedentary lifestyles. In brief, a historical review of the discoveries of the causes of human cancer is presented with extended discussions of the difficulties encountered in identifying viral causes of cancer. PMID- 26862498 TI - Synthetic cannabinoids 2015: An update for pediatricians in clinical practice. AB - Synthetic cannabinoids are a group of substances in the world of designer drugs that have become increasingly popular over the past few years. Synthetic cannabinoids are a chemically diverse group of compounds functionally similar to THC. Since first appearing on the world market a few years ago these compounds have evolved rapidly. Newer more potent analogues have been developed. Identifying youth who abuse these substances can be difficult. Newer forms of consumption have also evolved. These products are now manufactured in products that look like natural cannabis resin and in liquid cartridges used in electronic cigarettes. Synthetic cannabinoids appear to be associated with potentially dangerous health effects that are more severe than that of marijuana. Some synthetic cannabinoid compounds have been associated with serious physical consequences, such as, seizures, myocardial infarction and renal damage. In addition, psychoactive effects, such as aggression, confusion, anxiety and psychosis have also been reported. The diagnosis remains primarily clinical with toxicological confirmation difficult due to manufacturers constantly developing new analogues to avoid detection. Pediatricians are urged to familiarize themselves with these drugs and the typical presentations of patients who use them. PMID- 26862497 TI - Cardiovascular magnetic resonance: Diagnostic utility and specific considerations in the pediatric population. AB - Cardiovascular magnetic resonance is a non-invasive imaging modality which is emerging as important tool for the investigation and management of pediatric cardiovascular disease. In this review we describe the key technical and practical differences between scanning children and adults, and highlight some important considerations that must be taken into account for this patient population. Using case examples commonly seen in clinical practice, we discuss the important clinical applications of cardiovascular magnetic resonance, and briefly highlight key future developments in this field. PMID- 26862501 TI - Sublingual immunotherapy for pediatric allergic rhinitis: The clinical evidence. AB - Allergic rhinitis is estimated to affect 10%-20% of pediatric population and it is caused by the IgE-sensitization to environmental allergens, most importantly grass pollens and house dust mites. Allergic rhinitis can influence patient's daily activity severely and may precede the development of asthma, especially if it is not diagnosed and treated correctly. In addition to subcutaneous immunotherapy, sublingual immunotherapy (SLIT) represents the only treatment being potentially able to cure allergic respiratory diseases, by modulating the immune system activity. This review clearly summarizes and analyzes the available randomized, double-blinded, placebo-controlled trials, which aimed at evaluating the effectiveness and the safety of grass pollen and house dust mite SLIT for the specific treatment of pediatric allergic rhinitis. Our analysis demonstrates the good evidence supporting the efficacy of SLIT for allergic rhinitis to grass pollens in children, whereas trials regarding pediatric allergic rhinitis to house dust mites present lower quality, although several studies supported its usefulness. PMID- 26862499 TI - Novel insights in the management of sickle cell disease in childhood. AB - Sickle cell disease (SCD) is a life-threatening genetic disorder characterized by chronic hemolytic anemia, vascular injury and multiorgan dysfunctions. Over the last few decades, there have been significant improvements in SCD management in Western countries, especially in pediatric population. An early onset of prophylaxis with Penicillin and a proper treatment of the infections have increased the overall survival in childhood. Nevertheless, management of painful episodes and prevention of organ damage are still challenging and more efforts are needed to better understand the mechanisms behind the development of chronic organ damages. Hydroxyurea (Hydroxycarbamide, HU), the only medication approved as a disease-modifying agent by the United States Food and Drug Administration and the European Medicines Agency, is usually under-used, especially in developing countries. Currently, hematopoietic stem-cell transplantation is considered the only curative option, although its use is limited by lack of donors and transplant-related toxicity. SCD symptoms are similar in children and adults, but complications and systemic organ damages increase with age, leading to early mortality worldwide. Experts in comprehensive care of young patients with SCD, especially those approaching the transition age to adulthood, are missing, leading people to rely on urgent care, increasing health care utilization costs and inappropriate treatments. It would be important to establish programs of comprehensive healthcare for patients with SCD from birth to adulthood, to improve their quality and expectancy of life. PMID- 26862500 TI - Retinopathy of prematurity: Past, present and future. AB - Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina occurring principally in new born preterm infants. It is an avoidable cause of childhood blindness. With the increase in the survival of preterm babies, ROP has become the leading cause of preventable childhood blindness throughout the world. A simple screening test done within a few weeks after birth by an ophthalmologist can avoid this preventable blindness. Although screening guidelines and protocols are strictly followed in the developed nations, it lacks in developing economies like India and China, which have the highest number of preterm deliveries in the world. The burden of this blindness in these countries is set to increase tremendously in the future, if corrective steps are not taken immediately. ROP first emerged in 1940s and 1950s, when it was called retrolental fibroplasia. Several epidemics of this disease were and are still occurring in different regions of the world and since then a lot of research has been done on this disease. However, till date very few comprehensive review articles covering all the aspects of ROP are published. This review highlights the past, present and future strategies in managing this disease. It would help the pediatricians to update their current knowledge on ROP. PMID- 26862502 TI - Clinical spectrum of primary ciliary dyskinesia in childhood. AB - Although the triad of bronchiectasis, sinusitis and situs inversus was first described by Kartagener in 1933, the clinical spectrum of primary ciliary dyskinesia is still under investigation. Heterotaxy defects as well as upper and lower respiratory tract symptoms are the main manifestations in childhood. It is now recognized that situs inversus is encountered in only half of patients. The first lower respiratory symptoms may be present from infancy as neonatal respiratory distress. The most common lower airway manifestations are chronic wet cough, recurrent pneumonia and therapy resistant wheezing. Patients are at risk of developing bronchiectasis which may even be the presenting finding due to delayed diagnosis. Upper respiratory tract infections such as nasal congestion, nasal drainage and recurrent sinusitis as well as otologic manifestations such as otitis media or otorrhea with conductive hearing loss are also often encountered. It seems that the type of ciliary ultrastructure defects and the involved mutated genes are associated to some extent to the clinical profile. The disease, even in nowadays, is not recognized at an early age and the primary care clinician should have knowledge of its clinical spectrum in order to select appropriately the children who need further investigation for the diagnosis of this disorder. PMID- 26862503 TI - Cutting-edge technologies for diagnosis and monitoring of snoring in children. AB - Snoring is a very common problem in children and may be an indication of obstructive sleep apnea (OSA). Appropriate diagnosis is of importance due to detrimental effects of OSA. Polysomnography is considered the gold standard for the diagnosis of OSA. However, it is impractical for several reasons and this is why other tests have been developed as alternatives to formal polysomnography (PSG) for the assessment of children with snoring. In this mini-review basic features of PSG as well as alternative tests are presented and future perspectives are provided in addition to current guideline for the diagnosis and monitoring of childhood snoring. The aim of this review is to highlight briefly currently developed technologies that seem promising for the evaluation of snoring. PMID- 26862504 TI - Short and long term prognosis in perinatal asphyxia: An update. AB - Interruption of blood flow and gas exchange to the fetus in the perinatal period, known as perinatal asphyxia, can, if significant, trigger a cascade of neuronal injury, leading on to neonatal encephalopathy (NE) and resultant long-term damage. While the majority of infants who are exposed to perinatal hypoxia ischaemia will recover quickly and go on to have a completely normal survival, a proportion will suffer from an evolving clinical encephalopathy termed hypoxic ischaemic encephalopathy (HIE) or NE if the diagnosis is unclear. Resultant complications of HIE/NE are wide-ranging and may affect the motor, sensory, cognitive and behavioural outcome of the child. The advent of therapeutic hypothermia as a neuroprotective treatment for those with moderate and severe encephalopathy has improved prognosis. Outcome prediction in these infants has changed, but is more important than ever, as hypothermia is a time sensitive intervention, with a very narrow therapeutic window. To identify those who will benefit from current and emerging neuroprotective therapies we must be able to establish the severity of their injury soon after birth. Currently available indicators such as blood biochemistry, clinical examination and electrophysiology are limited. Emerging biological and physiological markers have the potential to improve our ability to select those infants who will benefit most from intervention. Biomarkers identified from work in proteomics, metabolomics and transcriptomics as well as physiological markers such as heart rate variability, EEG analysis and radiological imaging when combined with neuroprotective measures have the potential to improve outcome in HIE/NE. The aim of this review is to give an overview of the literature in regards to short and long-term outcome following perinatal asphyxia, and to discuss the prediction of this outcome in the early hours after birth when intervention is most crucial; looking at both currently available tools and introducing novel markers. PMID- 26862505 TI - Oral medications regarding their safety and efficacy in the management of patent ductus arteriosus. AB - Patent ductus arteriosus (PDA) is a common clinical condition in preterm infants which is inversely related to birth weight and gestational age. Cyclooxygenase inhibitors such as indomethacin and ibuprofen which block the prostaglandin conversion from arachidonic acid are the most commonly used drugs for ductal closure. This review focuses on the safety and efficacy oral medications in the management of PDA in preterm infants. Ibuprofen seems to be the first choice due to its higher safety profile, as it is associated with fewer gastrointestinal and renal side effects when compared to indomethacin. PDA closure rates are better with oral than with intravenous ibuprofen probably due to the pharmacokinetic of the drug. However, these medications were reported to be associated with several adverse including transient renal failure, gastrointestinal bleeding and perforation, hyperbilirubinemia and platelet dysfunction. Paracetamol seems be an alternative to PDA therapy with lower adverse events and side effects. PMID- 26862507 TI - Validation of a pediatric bedside tool to predict time to death after withdrawal of life support. AB - AIM: To evaluate the accuracy of a tool developed to predict timing of death following withdrawal of life support in children. METHODS: Pertinent variables for all pediatric deaths (age <= 21 years) from 1/2009 to 6/2014 in our pediatric intensive care unit (PICU) were extracted through a detailed review of the medical records. As originally described, a recently developed tool that predicts timing of death in children following withdrawal of life support (dallas predictor tool [DPT]) was used to calculate individual scores for each patient. Individual scores were calculated for prediction of death within 30 min (DPT30) and within 60 min (DPT60). For various resulting DPT30 and DPT60 scores, sensitivity, specificity and area under the receiver operating characteristic curve were calculated. RESULTS: There were 8829 PICU admissions resulting in 132 (1.5%) deaths. Death followed withdrawal of life support in 70 patients (53%). After excluding subjects with insufficient data to calculate DPT scores, 62 subjects were analyzed. Average age of patients was 5.3 years (SD: 6.9), median time to death after withdrawal of life support was 25 min (range; 7 min to 16 h 54 min). Respiratory failure, shock and sepsis were the most common diagnoses. Thirty-seven patients (59.6%) died within 30 min of withdrawal of life support and 52 (83.8%) died within 60 min. DPT30 scores ranged from -17 to 16. A DPT30 score >= -3 was most predictive of death within that time period, with sensitivity = 0.76, specificity = 0.52, AUC = 0.69 and an overall classification accuracy = 66.1%. DPT60 scores ranged from -21 to 28. A DPT60 score >= -9 was most predictive of death within that time period, with sensitivity = 0.75, specificity = 0.80, AUC = 0.85 and an overall classification accuracy = 75.8%. CONCLUSION: In this external cohort, the DPT is clinically relevant in predicting time from withdrawal of life support to death. In our patients, the DPT is more useful in predicting death within 60 min of withdrawal of life support than within 30 min. Furthermore, our analysis suggests optimal cut-off scores. Additional calibration and modifications of this important tool could help guide the intensive care team and families considering DCD. PMID- 26862508 TI - Analysis of the therapeutic evolution in the management of airway infantile hemangioma. AB - AIM: To analyze the evolution in the management of airway infantile hemangioma (AIH) and to report the results from 3 pediatric tertiary care institutions. METHODS: A retrospective study of patients with diagnosis of AIH and treated in 3 pediatric tertiary care institutions from 1996 to 2014 was performed. RESULTS: Twenty-three patients with diagnosis of AIH were identified. Mean age at diagnosis was 6 mo (range, 1-27). Single therapy was indicated in 16 patients and 7 patients received combined therapy. Two therapeutic groups were identified: Group A included 14 patients who were treated with steroids, interferon, laser therapy and/or surgery; group B included 9 patients treated with oral propranolol. In group A, oral corticosteroids were used in 9 patients with a good response in 3 cases (no requiring other therapeutic option), the other patients required additional treatment options. Cushing syndrome was observed in 3 patients. One patient died of a fulminant sepsis. Open surgical excision and endoscopic therapy were performed in 11 patients (in 5 of them as a single treatment) with a response rate of 54.5%. Stridor persisted in 2 cases, and one patient died during the clinical course of bronchial aspiration. In group B, oral propranolol was used in 9 patients (in 8 of them as a single treatment) with a response rate of 100%, with an mean treatment duration of 7 mo (range, 5-10); complications were not observed. CONCLUSION: Our experience and the medical literature support the use of propranolol as a first line of treatment in AIH. PMID- 26862506 TI - Current views of the relationship between Helicobacter pylori and Henoch Schonlein purpura in children. AB - Helicobacter pylori (H. pylori) is one of the factors involved in the pathogenesis of various gastrointestinal diseases and may play a potential role in certain extra-intestinal diseases. H. pylori infection are mainly acquired during childhood, and it has been reported that in endemic areas of China the infection rates are extraordinarily higher in HSP children, particular those with abdominal manifestations. Furthermore, eradication therapy may ameliorate Henoch Schonlein purpura (HSP) manifestations and decrease the recurrence of HSP. Therefore, results suggested that detection of H. pylori infection by appropriate method ought to be applied in HSP children. Current evidences indicate that local injury of gastric mucosa and immunological events induced by H. pylori infection are involved in the development of HSP. Increased serum IgA, cryoglobulins, C3 levels, autoimmunity, proinflammatory substances and molecular mimicry inducing immune complex and cross-reactive antibodies caused by H. pylori infection might play their roles in the course of HSP. However, there are no investigations confirming the causality between H. pylori infection and HSP, and the pathogenesis mechanism is still unclear. More bench and clinical studies need to be executed to elaborate the complex association between H. pylori and HSP. PMID- 26862509 TI - Expression of pain and distress in children during dental extractions through drawings as a projective measure: A clinical study. AB - AIM: To evaluate the efficacy of drawings as a projective measure of pain and distress in children undergoing dental extractions. METHODS: Children in the age range of 4-13 years with existence of untreatable caries or over-retained primary teeth, indicated for extractions were included. Pain was assessed using one behavioral [faces, legs, activity, cry and consolability (FLACC)] scale; and a self report measure; faces pain scale-revised (FPS-R), at two points of time, after completion of local anesthetic administration and after extraction. The general behavior of children was assessed with Wright's modification of Frankl rating scale. At the end of the session, children were instructed to represent, themselves along with the dentist and their experiences of the dental treatment through drawing. The drawings were scored utilizing Child drawing: Hospital scale (CD: H) manual and correlated with FLACC, FPS-R and Frankl using Pearson correlation test. RESULTS: A positive correlation, though statistically not significant, was observed between CD: H scores and all other considered parameters (Frankl, FPS-R and FLACC) in the present study. CONCLUSION: Drawings could not act as surrogate measure of child's pain; however, they acted as a narrative of his/her experiences and reflection of inner emotions. Hence, drawings can be used as an additional dental armamentarium. PMID- 26862510 TI - Dental knowledge and awareness among grandparents. AB - AIM: To investigate grandparent's knowledge and awareness about the oral health of their grandchildren. METHODS: Grandparents accompanying patients aged 4-8 years, who were living with their grandchildren and caring for them for a major part of the day, when both their parents were at work were included in the study. A 20-item questionnaire covering socio-demographic characteristics, dietary and oral hygiene practices was distributed to them. The sample comprised of 200 grandparents (59 males, 141 females). chi(2) analysis and Gamma test of symmetrical measures were applied to assess responses across respondent gender and level of education. RESULTS: Oral health related awareness was found to be low among grandparents. In most questions asked, grandparents with a higher level of education exhibited a better knowledge about children's oral health. Level of awareness was not related to their gender. CONCLUSION: Oral hygiene and dietary habits are established during childhood. There is a great need for dental education of grandparents as they serve as role models for young children. PMID- 26862511 TI - Effects of carob-bean gum thickened formulas on infants' reflux and tolerance indices. AB - AIM: To examine the effect of carob-bean gum (CBG) thickened-formulas on reflux and tolerance indices in infants with gastro-esophageal reflux (GER). METHODS: Fifty-six eligible infants (1-6 mo old) were randomly allocated to receive for two weeks a formula with either 0.33 g/100 mL (Formula A) or 0.45 g/100 mL (Formula B) of cold soluble CBG galactomannans respectively, or a formula with 0.45 g/100 mL of hot soluble CBG galactomannans (Formula C). No control group receiving standard formula was included in the study. Data on the following indices were obtained both at baseline and follow-up from all study participants: 24 h esophageal pH monitoring indices, anthropometrical indices (i.e., body weight and length) and tolerance indices (i.e., frequency of colics; type and frequency of defecations). From the eligible infants, forty seven were included in an intention-to-treat analysis to examine the effects of the two-week trial on esophageal 24 h pH monitoring, growth and tolerance indices. Repeated Measures ANOVA was used to examine the research hypothesis. RESULTS: Regarding changes in 24 h pH monitoring indices, significant decreases from baseline to follow-up were observed in the "Boix Ochoa Score" (i.e., an index of esophageal acid exposure), in the total number of visible refluxes and in all symptoms related indices due to acid reflux only for infants provided with Formula A, while no significant changes were observed for infants provided with Formulas B and C. In addition, the significant decreases observed in two symptoms related pH monitoring indices (i.e., "Symptom index for reflux" and "Percentage of all reflux") for infants provided with Formula A were also found to differentiate significantly compared to the changes observed in the other two groups (P = 0.048 and P = 0.014 respectively). Concerning changes in anthropometric indices, body weight significantly increased among infants provided with Formulas A and C, but not for infants provided with Formula B. As far as tolerance indices were concerned, the numbers of total and diarrheic defecations increased significantly only in infants provided with Formula B and these changes were significantly higher compared to the decreases observed in infants fed with Formulas A and C (P = 0.003 and P = 0.015 respectively. Lastly the number of colics significantly decreased in all infants, irrespective of the tested formula. CONCLUSION: Formula A (i.e., 0.33 g/100 mL of cold galactomannans) was effective in reducing certain pH-monitoring indices of uncomplicated GER, increased body weight and was well tolerated by infants. PMID- 26862512 TI - Tourette syndrome associated with attention deficit hyperactivity disorder: The impact of tics and psychopharmacological treatment options. AB - Tourette syndrome (TS) is a neurodevelopmental disorder characterized by multiple chronic motor and vocal tics beginning in childhood. Several studies describe the association between TS and attention deficit hyperactivity disorder (ADHD). Fifty percent of children diagnosed with ADHD have comorbid tic disorder. ADHD related symptoms have been reported in 35% to 90% of children with TS. Since ADHD is the most prevalent comorbid condition with TS and those with concomitant TS and ADHD present with considerable psychosocial and behavioral impairments, it is essential for clinicians to be familiar with these diagnoses and their management. This paper highlights the association between treating ADHD with stimulants and the development of tic disorders. The two cases discussed underscore the fact that children with TS may present with ADHD symptomatology prior to the appearance of any TS related symptoms. Appropriate management of TS in a patient diagnosed with ADHD can lead to quality of life improvements and a reduction in psychosocial impairments. PMID- 26862513 TI - Acute lobar nephritis in children: Not so easy to recognize and manage. AB - Acute lobar nephritis (ALN) is a localized non-liquefactive inflammatory renal bacterial infection, which typically involves one or more lobes. ALN is considered to be a midpoint in the spectrum of upper urinary tract infection, a spectrum ranging from uncomplicated pyelonephritis to intrarenal abscess. This condition may be difficult to recognize due to the lack of specific symptoms and laboratory findings. Therefore the disease is probably underdiagnosed. Computed tomography scanning represents the diagnostic gold standard for ALN, but magnetic resonance imagine could be considered in order to limit irradiation. The diagnosis is relevant since initial intravenous antibiotic therapy and overall length of treatment should not be shorter than 3 wk. We review the literature and analyze the ALN clinical presentation starting from four cases with the aim to give to the clinicians the elements to suspect and recognize the ALN in children. PMID- 26862514 TI - Developmental ossification sequences of the appendicular and axial skeleton in Kuttanad duck embryos (Anas platyrhynchos domesticus). AB - The processes of ossification sequences are poorly investigated for birds in general, even for domestic and experimental species and when it comes to the waterfowl it is almost negligible. Such sequences constitute a rich source of data on character evolution, and may even provide phylogenetic information. A pre hatch developmental study on ossification sequences of axial and appendicular skeletal system in Kuttanad duck embryos was undertaken using 78 viable embryos. From day 3 to day 7 of incubation no ossification densities were seen both by alizarin red staining and computerized radiography. The first indication of ossification as small ossification centers in skull bones, clavicle, scapula, humerus, radius and ulna in forelimb and ilium, pubis femur and fibula in hind limb were observed on the 9(th) day of incubation. The ossification of the body of the ribs started at the 11(th) day of incubation towards the proximal extremity. On day 13(th) the ossification process of vertebrae was started from cervical end. The variation in appearance of the ossification centers in different bones at different stages of incubation period suggests relative importance of phylogeny to the sequences. PMID- 26862515 TI - Post-surgical treatment of thyroid carcinoma in dogs with retinoic acid 9 cis improves patient outcome. AB - The objective of the present study was to compare the effects of isotretinoin 9 cis (RA9-cis) as a post-surgery treatment of thyroid carcinoma to a traditional treatment (doxorubicin) and no treatment. Owners who did not want their dogs to receive treatment were placed into the control group A (GA; n=10). The remaining dogs were randomly placed into either group B (GB; n=12) and received doxorubicin at a dose of 30 mg/m(2) every three weeks, for six complete cycles or group C (GC; n=15) and treated with RA9-cis at a dose of 2 mg/kg/day for 6 months. The time of the recurrence was significantly shorter in the GA and GB compared to GC (P=0.0007; P=0.0015 respectively), while we did not detect differences between GA and GB. The hazard ratio of recurrence between GA and GB compared to GC were 7.25 and 5.60 times shorter, respectively. We did not detect any differences between the other groups. The risk ratio of recurrence was 2.0 times higher in GA compared to GC and 2.1 times higher in GB compared to GC. The type of carcinoma had an effect on time of survival with follicular carcinomas having an increased mean survival time than follicular-compact carcinomas (P<0.0001) and follicular compact carcinomas had a longer mean survival time than compact carcinomas. The interaction among treatment and type was significant, but survival time in follicular carcinomas did not differ between treatments. In follicular-compact carcinomas the survival time of GC was greater than GB (P<0.05), but we did not detect a difference between GA and GB. In conclusion, this study shows that the use of surgery in combination with RA9-cis treatment significantly increases survival rate and decreases the time to tumor recurrence when compared to doxorubicin treated or untreated dogs. The histological type of carcinoma interacted with treatment for time to recurrence and survival time, with more undifferentiated carcinomas having a worse prognosis than differentiated carcinomas. PMID- 26862516 TI - The pulsed light inactivation of veterinary relevant microbial biofilms and the use of a RTPCR assay to detect parasite species within biofilm structures. AB - The presence of pathogenic organisms namely parasite species and bacteria in biofilms in veterinary settings, is a public health concern in relation to human and animal exposure. Veterinary clinics represent a significant risk factor for the transfer of pathogens from housed animals to humans, especially in cases of wound infection and the shedding of faecal matter. This study aims to provide a means of detecting veterinary relevant parasite species in bacterial biofilms, and to provide a means of disinfecting these biofilms. A real time PCR assay was utilized to detect parasite DNA in Bacillus cereus biofilms on stainless steel and PVC surfaces. Results show that both Cryptosporidium and Giardia attach to biofilms in large numbers (100-1000 oo/cysts) in as little as 72 hours. Pulsed light successfully inactivated all test species (Listeria, Salmonella, Bacillus, Escherichia) in planktonic and biofilm form with an increase in inactivation for every increase in UV dose. PMID- 26862517 TI - MicroRNA Expression in beta-Thalassemia and Sickle Cell Disease: A Role in The Induction of Fetal Hemoglobin. AB - Today the regulatory role of microRNAs (miRs) is well characterized in many diverse cel- lular processes. MiR-based regulation is categorized under epigenetic regulatory mecha- nisms. These small non-coding RNAs participate in producing and maturing erythrocytes, expressing hematopoietic factors and regulating expression of globin genes by post-tran- scriptional gene silencing. The changes in expression of miRs (miR-144/-320/-451/-503) in thalassemic/sickle cells compared with normal erythrocytes may cause clinical severity. According to the suppressive effects of certain miRs (miR-15a/-16-1/-23a/-26b/-27a/-451) on a number of transcription factors [myeloblastosis oncogene (MYB), B-cell lymphoma 11A (BCL11A), GATA1, Kruppel-like factor 3 (KLF3) and specificity protein 1 (Sp1)] during beta globin gene expression, It has been possible to increasing gamma globin gene expression and fetal hemoglobin (HbF) production. Therefore, this strategy can be used as a novel therapy in infusing HbF and improving clinical complications of patients with hemoglobi- nopathies. PMID- 26862518 TI - Down-Regulatory Effects of miR-211 on Long Non-Coding RNA SOX2OT and SOX2 Genes in Esophageal Squamous Cell Carcinoma. AB - OBJECTIVE: MicroRNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) that tran- scriptionally or post-transcriptionally regulate gene expression through degradation of their mRNA targets and/or translational suppression. However, there are a few reports on miRNA-mediated expression regulation of long ncRNAs (lncRNAs). We have previ- ously reported a significant upregulation of the lncRNA SOX2OT and its intronic cod- ing gene, SOX2, in esophageal squamous cell carcinoma (ESCC) tissue samples. In this study, we aimed to evaluate the effect of induced overexpression of miR-211 on SOX2OT and SOX2 expression in vitro. MATERIALS AND METHODS: In this experimental study, we performed both bioinformatic and experimental analyses to examine whether these transcripts are regulated by miRNAs. From the list of potential candidate miRNAs, miR-211 was found to have complementary sequences to SOX2OT and SOX2 transcripts. To validate our finding experimentally, we transfected the NT-2 pluripotent cell line (an embryonal carcinoma stem cell) with an expression vector overexpressing miR-211. The expression chang- es of miR-211, SOX2OT, and SOX2 were then quantified by a real-time polymerase chain reaction (RT-PCR) approach. RESULTS: Compared with mock-transfected cells, overexpression of miR-211 caused a significant down regulation of both genes (P<0.05). Furthermore, flow-cytometry analysis revealed a significant elevation in sub-G1 cell population following ectopic expression of miR-211 in NT-2 cells. CONCLUSION: We report here, for the first time, the down regulation of SOX2OT and SOX2 genes by an miRNA. Considering the vital role of SOX2OT and SOX2 genes in pluripotency and tumorigenesis, our data suggest an important and inhibitory role for miR-211 in the aforementioned processes. PMID- 26862519 TI - The Effect of Lactobacillus crispatus and Lactobacillus rhamnosusCulture Supernatants on Expression of Autophagy Genes and HPV E6 and E7 Oncogenes in The HeLa Cell Line. AB - OBJECTIVE: The aim of this study was to clarify the mechanism by which lactobacilli exert their cytotoxic effects on cervical cancer cells. In addition, we aimed to evalu- ate the effect of lactobacilli on the expression of human papilloma virus (HPV) onco- genes. MATERIALS AND METHODS: In this experimental study, using quantitative real-time polymer- ase chain reaction (PCR), we analyzed the expression of CASP3 and three autophagy genes [ATG14, BECN1 and alpha 2 catalytic subunit of AMPK (PRKAA2)] along with HPV18 E6 and E7 genes in HeLa cells before and after treatment with Lactobacillus crispatus and Lactobacillus rhamnosus culture supernatants. RESULTS: The expression of CASP3 and autophagy genes in HeLa cells was de- creased after treatment with lactobacilli culture supernatants. However, this de- crease was not significant for PRKAA2 when compared with controls. In addition, expression of HPV E6 was significantly decreased after treatment with lactobacilli culture supernatants. CONCLUSION: Lactobacilli culture supernatants can decrease expression of ATG14 and BECN1 as well as the HPV E6 oncogene. It has been demonstrated that the main changes occurring during cervical carcinogenesis in cell machinery can be reversed by suppression of HPV oncogenes. Therefore, downregulation of HPV E6 by lacto- bacilli may have therapeutic potential for cervical cancer. As the role of autophagy in cancer is complicated, further work is required to clarify the link between downregula- tion of autophagy genes and antiproliferative effects exerted by lactobacilli. PMID- 26862520 TI - Altered Expression of High Molecular Weight Heat Shock Proteins after OCT4B1 Suppression in Human Tumor Cell Lines. AB - OBJECTIVE: OCT4B1, a novel variant of OCT4, is expressed in cancer cell lines and tis- sues. Based on our previous reports, OCT4B1 appears to have a crucial role in regulating apoptosis as well as stress response [heat shock proteins (HSPs)] pathways. The aim of the present study was to determine the effects of OCT4B1 silencing on the expression of high molecular weight HSPs in three different human tumor cell lines. MATERIALS AND METHODS: In this experimental study, OCT4B1 expression was suppressed in AGS (gastric adenocarcinoma), 5637 (bladder tumor) and U-87MG (brain tumor) cell lines using RNAi strategy. Real-time polymerase chain reaction (PCR) array was em- ployed for expression level analysis and the fold changes were calculated using RT2 Pro- filer PCR array data analysis software version 3.5. RESULTS: Our data revealed up-regulation of HSPD1 (from HSP60 family) as well as HSPA14, HSPA1L, HSPA4, HSPA5 and HSPA8 (from HSP70 family) following OCT4B1 knock-down in all three cell lines. In contrast, the expression of HSP90AA1 and HSP90AB1 (from HSP90 family) as well as HSPA1B and HSPA6 (from HSP70 family) was down-regulated under similar conditions. Other stress-related genes showed varying ex- pression pattern in the examined tumor cell lines. CONCLUSION: Our data suggest a direct or indirect correlation between the expression of OCT4B1 and HSP90 gene family. However, OCT4B1 expression was not strongly corre- lated with the expression of HSP70 and HSP60 gene families. PMID- 26862521 TI - STAT3 is Overactivated in Gastric Cancer Stem-Like Cells. AB - OBJECTIVE: Gastric cancer (GC) is widely associated with chronic inflammation. The pro inflammatory microenvironment provides conditions that disrupt stem/progenitor cell proliferation and differentiation. The signal transducer and activator of transcrip- tion-3 (STAT3) signaling pathway is involved in inflammation and also contributes to the maintenance of embryonic stem cell (ESCs) pluripotency. Here, we have investi- gated the activation status of STAT3 in GC stem-like cells (GCSLCs). MATERIALS AND METHODS: In this experimental research, CSLCs derived from the human GC cell line MKN-45 and patient specimens, through spheroid body formation, character- ized and then assayed for the STAT3 transcription factor expression in mRNA and protein level further to its activation. RESULTS: Spheroid cells showed higher potential for spheroid formation than the pa- rental cells. Furthemore, stemness genes NANOG, c-MYC and SOX-2 were over expressed in spheroids of MKN-45 and in patient samples. In MKN 45 spheroid cells, epithelial mesenchymal transition (EMT) related markers CDH2, SNAIL2, TWIST and VIMENTIN were upregulated (P<0.05), but we observed no change in expression of the E-cadherin epithelial marker. These cells exhibited more resistance to docetaxel (DTX) when compared with parental cells (P<0.05) according to the MTS assay. Al- though immunostaining and Western blotting showed expression of the STAT3 pro- tein in both spheroids and parents, the mRNA level of STAT3 in spheroids was higher than the parents. Nuclear translocation of STAT3 was accompanied by more intensive phospho-STAT3 (p-STAT3) in spheroid structures relative to the parent cells accord- ing to flow cytometry analysis (P<0.05). CONCLUSION: The present findings point to STAT3 over activation in GCSLCs. Com- plementary experiments are required to extend the role of STAT3 in stemness fea- tures and invasion properties of GCSCs and to consider the STAT3 pathway for CSC targeted therapy. PMID- 26862523 TI - Migration of Bone Marrow-Derived Very Small Embryonic-Like Stem Cells toward An Injured Spinal Cord. AB - OBJECTIVE: Bone marrow (BM) is one of the major hematopoietic organs in postnatal life that consists of a heterogeneous population of stem cells which have been previously described. Recently, a rare population of stem cells that are called very small embryonic-like (VSEL) stem cells has been found in the BM. These cells express several developmental markers of pluri- potent stem cells and can be mobilized into peripheral blood (PB) in response to tissue injury. In this study we have attempted to investigate the ability of these cells to migrate toward an injured spinal cord after transplantation through the tail vein in a rat model. MATERIALS AND METHODS: In this experimental study, VSELs were isolated from total BM cells using a fluorescent activated cell sorting (FACS) system and sca1 and stage specific embryonic antigen (SSEA-1) antibodies. After isolation, VSELs were cultured for 7 days on C2C12 as the feeder layer. Then, VSELs were labeled with 1,1'-dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine perchlorate (DiI) and transplanted into the rat spinal cord injury (SCI) model via the tail vein. Finally, we sought to determine the presence of VSELs in the lesion site. RESULTS: We isolated a high number of VSELs from the BM. After cultivation, the VSELs colonies were positive for SSEA-1, Oct4 and Sca1. At one month after transplantation, real-time polymerase chain reaction analysis confirmed a significantly increased expres- sion level of Oct4 and SSEA-1 positive cells at the injury site. CONCLUSION: VSELs have the capability to migrate and localize in an injured spinal cord after transplantation. PMID- 26862522 TI - Improved Survival and Hematopoietic Differentiation of Murine Embryonic Stem Cells on Electrospun Polycaprolactone Nanofiber. AB - OBJECTIVE: Three-dimensional (3D) biomimetic nanofiber scaffolds have widespread ap- plications in biomedical tissue engineering. They provide a suitable environment for cel- lular adhesion, survival, proliferation and differentiation, guide new tissue formation and development, and are one of the outstanding goals of tissue engineering. Electrospinning has recently emerged as a leading technique for producing biomimetic scaffolds with mi- cro to nanoscale topography and a high porosity similar to the natural extracellular matrix (ECM). These scaffolds are comprised of synthetic and natural polymers for tissue engi- neering applications. Several kinds of cells such as human embryonic stem cells (hESCs) and mouse ESCs (mESCs) have been cultured and differentiated on nanofiber scaffolds. mESCs can be induced to differentiate into a particular cell lineage when cultured as em- bryoid bodies (EBs) on nano-sized scaffolds. MATERIALS AND METHODS: We cultured mESCs (2500 cells/100 ul) in 96-well plates with knockout Dulbecco's modified eagle medium (DMEM-KO) and Roswell Park Memorial Institute 1640 (RPMI-1640), both supplemented with 20% ESC grade fetal bovine serum (FBS) and essential factors in the presence of leukemia inhibitory factor (LIF). mESCs were seeded at a density of 2500 cells/100 ul onto electrospun polycaprolactone (PCL) nanofibers in 96-well plates. The control group comprised mESCs grown on tissue cul- ture plates (TCP) at a density of 2500 cells/100 ul. Differentiation of mESCs into mouse hematopoietic stem cells (mHSCs) was performed by stem cell factor (SCF), interleukin-3 (IL-3), IL-6 and Fms-related tyrosine kinase ligand (Flt3-L) cytokines for both the PCL and TCP groups. We performed an experimental study of mESCs differentiation. RESULTS: PCL was compared to conventional TCP for survival and differentiation of mESCs to mHSCs. There were significantly more mESCs in the PCL group. Flowcyto- metric analysis revealed differences in hematopoietic differentiation between the PCL and TCP culture systems. There were more CD34+(Sca1+) and CD133+cells subpopulations in the PCL group compared to the conventional TCP culture system. CONCLUSION: The nanofiber scaffold, as an effective surface, improves survival and differentiation of mESCs into mHSCs compared to gelatin coated TCP. More studies are necessary to understand how the topographical features of electrospun fibers af- fect cell growth and behavior. This can be achieved by designing biomimetic scaffolds for tissue engineering. PMID- 26862525 TI - Histopathological Analysis from Gallic Acid Administration on Hippocampal Cell Density, Depression, and Anxiety Related Behaviors in A Trimethyltin Intoxication Model. AB - OBJECTIVE: The present study investigated the effects of gallic acid (GA) administration on trimethyltin chloride (TMT) induced anxiety, depression, and hippocampal neurodegen- eration in rats. MATERIALS AND METHODS: In this experimental study, the rats received intraperitoneal (i.p.) injections of TMT (8 mg/kg). The animals received either GA (50, 100 and 150 mg/kg) or saline as the vehicle for 14 consecutive days. We measured depression and anxiety levels of the rats by conducting the behavioral tail suspension (TST), elevatedplusmaze (EPM), and novelty suppressed feeding (NSF) tests. Histological analyses were then used to de- termine the cell densities of different hippocampal subdivisions. The data were analyzed with ANOVA and Tukey's post hoc test. RESULTS: GA administration ameliorated anxiety and depression in the behavioral tests. The cell densities in the CA1, CA2, CA3 and DG hippocampal subdivisionsfrom GA-treat- ed rats were higher than saline treated rats. CONCLUSION: GA treatment against TMT-induced hippocampal degeneration altered cellular loss in the hippocampus and ameliorated the depression-anxiety state in rats. PMID- 26862524 TI - Stage-Specific Profiling of Transforming Growth Factor-beta, Fibroblast Growth Factor and Wingless-int Signaling Pathways during Early Embryo Development in The Goat. AB - OBJECTIVE: This research intends to unravel the temporal expression profiles of genes in- volved in three developmentally important signaling pathways [transforming growth factor-beta (TGF-beta), fibroblast growth factor (FGF) and wingless/int (WNT)] during preand peri-implan- tation goat embryo development. MATERIALS AND METHODS: In this experimental study, we examined the transcripts that encoded the ligand, receptor, intracellular signal transducer and modifier, and the down- stream effector, for each signaling pathway. In vitro mature MII oocytes and embryos at three distinctive stages [8-16 cell stage, day-7 (D7) blastocysts and day-14 (D14) blas- tocysts] were separately prepared in triplicate for comparative real-time reverse tran- scriptase polymerase chain reaction (RT-PCR) using the selected gene sets. RESULTS: Most components of the three signaling pathways were present at more or less stable levels throughout the assessed oocyte and embryo developmental stages. The transcripts for TGF beta, FGF and WNT signaling pathways were all induced in unfertilized MII oocytes. However, developing embryos showed gradual patterns of decrease in the activities of TGF-beta, FGF and WNT components with renewal thereafter. CONCLUSION: The results suggested that TGF-beta, FGF and WNT are maternally active signaling pathways required during earlier, rather than later, stages of preand peri- implantation goat embryo development. PMID- 26862526 TI - Histological Study of Bone Marrow and Umbilical Cord Stromal Cell Transplantation in Regenerating Rat Peripheral Nerve. AB - OBJECTIVE: Bone marrow and umbilical cord stromal cells are multipotential stem cells that have the ability to produce growth factors that play an important role in survival and generation of axons. The goal of this study was to evaluate the effects of the two different mesenchymal stem cells on peripheral nerve regeneration. MATERIALS AND METHODS: In this experimental study, a 10 mm segment of the left sciatic nerve of male Wistar rats (250-300 g) was removed with a silicone tube interposed into this nerve gap. Bone marrow stromal cells (BMSCs) and human umbilical cord stromal cells (HUCSCs) were respectively obtained from rat and human. The cells were sepa- rately cultured and transplanted into the nerve gap. The sciatic nerve regeneration was evaluated by immunohistochemistry, and light and electron microscopy. Moreover, histo- morphology of the gastrocnemius muscle was observed. RESULTS: The nerve regeneration in the BMSCs and HUCSCs groups that had received the stem cells was significantly more favorable than the control group. In addition, the BM- SCs group was significantly more favorable than the HUCSCs group (P<0.05). CONCLUSION: The results of this study suggest that both homograft BMSCs and het- erograft HUCSCs may have the potential to regenerate peripheral nerve injury and transplantation of BMSCs may be more effective than HUCSCs in rat. PMID- 26862527 TI - The Effect of Estradiol and Progesterone on Toll Like Receptor Gene Expression in A Human Fallopian Tube Epithelial Cell Line. AB - OBJECTIVE: Toll like receptors (TLRs) are one of the main components of the innate im- mune system. It has been reported that expression of these receptors are altered in the female reproductive tract (FRT) during menstrual cycle. Here we used a fallopian tube epithelial cell line (OE-E6/E7) to evaluate the effect of two sex hormones in modulating TLR expression. MATERIALS AND METHODS: In this experimental study, initially TLR gene expression in OE- E6/E7 cells was evaluated and compared with that of fallopian tube tissue using quanti- tative real time-polymerase chain reaction (qRT-PCR) and immunostaining. Thereafter, OE E6/E7 cells were cultured with different concentrations of estradiol and progesterone, and combination of both. qRT-PCR was performed to reveal any changes in expression of TLR genes as a result of hormonal treatment. RESULTS: TLR1-10 genes were expressed in human fallopian tube tissue. TLR1-6 genes and their respective proteins were expressed in the OE-E6/E7 cell line. Although estradiol and progesterone separately had no significant effect on TLR expression, their combined treatment altered the expression of TLRs in this cell line. Also, the pattern of TLR expres- sion in preovulation (P), mensturation (M) and window of implantation (W) were the same for all TLRs with no significant differences between P, M and W groups. CONCLUSION: These data show the significant involvement of the combination of es- tradiol and progesterone in modulation of TLR gene expression in this human fal- lopian tube cell line. Further experiments may reveal the regulatory mechanism and signalling pathway behind the effect of sex hormones in modulating TLRs in the hu- man FRT. PMID- 26862528 TI - Human Neutrophil Elastase Induce Interleukin-10 Expression in Peripheral Blood Mononuclear Cells through Protein Kinase C Theta/Delta and Phospholipase Pathways. AB - OBJECTIVE: Neutrophils have an important role in the rapid innate immune response, and the release or active secretion of elastase from neutrophils is linked to various inflammatory responses. Purpose of this study was to determine how the human neutrophil elastase affects the interleukin-10 (IL-10) response in peripheral blood mononuclear cells (PBMC). MATERIALS AND METHODS: In this prospective study, changes in IL-10 messenger RNA (mRNA) and protein expression levels in monocytes derived from human PBMCs were investigated after stimulation with human neutrophil elastase (HNE). A set of inhibitors was used for examining the pathways for IL-10 production induced by HNE. RESULTS: Reverse transcription polymerase chain reaction (RT-PCR) showed that stimulation with HNE upregulated IL-10 mRNA expression by monocytes, while the enzyme-linked immunosorbent assay (ELISA) revealed an increase of IL-10 protein level in the culture medium. A phospholipase C inhibitor (U73122) partially blunt- ed the induction of IL-10 mRNA expression by HNE, while IL-10 mRNA expression was significantly reduced by a protein kinase C (PKC) inhibitor (Rottlerin). A calcium chelator (3,4,5 trimethoxybenzoic acid 8-(diethylamino)octyl ester: TMB-8) inhibited the response of IL-10 mRNA to stimulation by HNE. In addition, pretreatment with a broad spectrum PKC inhibitor (Ro-318425) partly blocked the response to HNE. Finally, an inhibitor of PKC theta/delta abolished the increased level of IL-10 mRNA expression. CONCLUSION: These results indicate that HNE mainly upregulates IL-10 mRNA ex- pression and protein production in moncytes via a novel PKC theta/delta, although partially via the conventional PKC pathway. PMID- 26862529 TI - In Vitro Differentiation of Insulin Secreting Cells from Mouse Bone Marrow Derived Stage-Specific Embryonic Antigen 1 Positive Stem Cells. AB - OBJECTIVE: Bone marrow has recently been recognized as a novel source of stem cells for the treatment of wide range of diseases. A number of studies on murine bone mar- row have shown a homogenous population of rare stage-specific embryonic antigen 1 (SSEA-1) positive cells that express markers of pluripotent stem cells. This study focuses on SSEA-1 positive cells isolated from murine bone marrow in an attempt to differentiate them into insulin-secreting cells (ISCs) in order to investigate their differentiation potential for future use in cell therapy. MATERIALS AND METHODS: This study is an experimental research. Mouse SSEA-1 positive cells were isolated by Magnetic-activated cell sorting (MACS) followed by characteriza- tion with flow cytometry. Induced SSEA-1 positive cells were differentiated into ISCs with specific differentiation media. In order to evaluate differentiation quality and analysis, dithizone (DTZ) staining was use, followed by reverse transcription polymerase chain reaction (RT-PCR), immunocytochemistry and insulin secretion assay. Statistical results were analyzed by one-way ANOVA. RESULTS: The results achieved in this study reveal that mouse bone marrow contains a population of SSEA-1 positive cells that expresses pluripotent stem cells markers such as SSEA-1, octamer-binding transcription factor 4 (OCT-4) detected by immunocytochem- istry and C-X-C chemokine receptor type 4 (CXCR4) and stem cell antigen-1 (SCA-1) detected by flow cytometric analysis. SSEA-1 positive cells can differentiate into ISCs cell clusters as evidenced by their DTZ positive staining and expression of genes such as Pdx1 (pancreatic transcription factors), Ngn3 (endocrine progenitor marker), Insulin1 and Insulin2 (pancreaticbeta-cell markers). Additionally, our results demonstrate expression of Pdx1 and Glut2 protein and insulin secretion in response to a glucose challenge in the differentiated cells. CONCLUSION: Our study clearly demonstrates the potential of SSEA-1 positive cells to differentiate into insulin secreting cells in defined culture conditions for clinical ap- plications. PMID- 26862530 TI - Diet-Induced Obesity and Ghrelin Effects on Pituitary Gonadotrophs: Immunohistomorphometric Study in Male Rats. AB - OBJECTIVE: The close relationship between energy metabolism, nutritional state, and reproductive physiology suggests that nutritional and metabolic disorders can disrupt normal reproductive function and fertility. Considering the importance of leptin and ghrelin effects in regulation of the hypothalamic-pituitary-gonadal axis, the objective of this study was to investigate the influence of obesity and centrally applied ghrelin on immunohistochemical appearance and quantitative morphology of the pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH) producing cells in adult male rats. MATERIALS AND METHODS: In this experimental study, animals were given two differ- ent diets: normal-fat (NF) and high-fat (HF), for 4 weeks, corresponding to normal and positive energy balance (n=2*14), respectively. Each group was subsequently divided into two subgroups (n=7) receiving intracerebroventricular (ICV) injections of either ghrelin [G, 1 ug/5 uL phosphate buffered saline (PBS)] or vehicle (5 uL PBS, control group) every 24 hours for five consecutive days. RESULTS: Morphometric analyses showed that in HF control group, the percentage of FSH cells per unit volume of total pituitary gland tissue (in MUm(3)), i.e. volume density (Vvc), was increased (P<0.05) by 9.1% in comparison with the NF controls. After ICV treatment with ghrelin, volume (Vc) and volume density (Vvc) of FSH cells in ghrelin+NF (GNF) and ghrelin+HF (GHF) groups remained unchanged in comparison with NF and HF controls. Volume of LH cells in HF control group was increased by 17% (P<0.05), but their Vvc was decreased by 8.3% (P<0.05) in comparison with NF controls. In GNF group, the volume of LH cells increased by 7% (P<0.05), in comparison with the NF controls, but in GHF group, the same parameter remained unchanged when compared with HF controls. The central application of ghrelin de- creased the Vvc of LH cells only in GNF group by 38.9% (P<0.05) in comparison with the NF control animals. CONCLUSION: The present study has shown that obesity and repetitive ICV administra- tion of low doses of ghrelin, in NF and HF rats, modulated the immunohistomorphometric features of gonadotrophs, indicating the importance of obesity and ghrelin in regulation of the reproductive function. PMID- 26862531 TI - Effects of Exendine-4 on The Differentiation of Insulin Producing Cells from Rat Adipose-Derived Mesenchymal Stem Cells. AB - OBJECTIVE: To evaluate the effect of Exendine-4 (EX-4), a Glucagon-like peptide 1 (GLP-1) receptor agonist, on the differentiation of insulin-secreting cells (IPCs) from rat adipose-derived mesenchymal stem cells(ADMSCs). MATERIALS AND METHODS: In this experimental study, ADMSCs were isolated from rat adi- pose tissue and exposed to induction media with or without EX-4. After induction, the existence of IPCs was confirmed by morphology analysis, expression pattern analysis of islet-specific genes (Pdx-1, Glut-2 and Insulin) and insulin synthesis and secretion. RESULTS: IPCs induced in presence of EX-4 were morphologically similar to pancre- atic islet-like cells. Expression of Pdx-1, Glut-2 and Insulin genes in EX-4 treated cells was significantly higher than the cells exposed to differentiation media without EX-4. Compared to EX-4 untreated ADMSCs, insulin release from EX-4 treated ADMSCs showed a nearly 2.5 fold (P<0.05) increase when exposed to a high glucose (25 mM) medium. The percentage of insulin positive cells in the EX-4 treated group was ap- proximately 4-fold higher than in the EX-4 untreated ADMSCs. CONCLUSION: The present study has demonstrated that EX-4 enhances the differen- tiation of ADMSCs into IPCs. Improvement of this method may help the formation of an unlimited source of cells for transplantation. PMID- 26862532 TI - Simultaneous Analysis of Wnt and NF-kappaB Signaling Pathways in Doxorubicin Sensitive and Methotrexate Resistant PLC/ PRF/5 Cells. AB - OBJECTIVE: Multi-drug resistance (MDR) is a controversial issue in traditional chemo- therapy of aggressive cancers, including hepatocellular carcinoma. The major cause of MDR is suggested to be the aberrant activation of the main signaling pathways such as Wnt and nuclear factor kappa-light-chain-enhancer of activated B cells (NF- kappaB) which have key roles in the maintenance of cancer stem cells (CSCs). Therefore, the evaluation of their alterations could be essential in chemo-resistant cancers such as Hepatocellular carcinoma. The main purpose of this study was to investigate the alteration of the mentioned pathways in the chemotherapy resistant cancer cells by assessing their major molecular parameters. MATERIALS AND METHODS: In this experimental study, methylthiazol tetrazolium (MTT) assay, acridine orange/ethidium bromide (AO/EtBr) and Hoechst 33342 staining, DNA fragmentation and colony formation methods were employed to investigate the cytotoxic effects of methotrexate (MTX) and doxorubicin (DOX) on PLC/PRF/5 cells. Moreover, the expression of 11 important genes involved in MDR was performed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: PLC/PRF/5 cells (Alexander) were sensitive to DOX and normally resist- ant to MTX. In addition, the results obtained from RT-PCR analysis revealed that beta-catenin expression was significantly reduced and ABCG2 significantly overex- pressed 4.85 and 3.34 times (P value<0.05) in DOX and MTX treated cells, respec- tively. Furthermore, a considerable expression of HIF 1alpha and p65 were detected only in MTX-resistant cells. CONCLUSION: Anti-cancer drugs may have more than one target in tumor cells. They not only participate in deregulation of Wnt but also alter NF-kappaB activation. Moreover, HIF-1alpha was the only anti-apoptotic protein that was significantly induced in the chem- oresistant cells. PMID- 26862534 TI - Protective Effect of Boric Acid on Oxidative DNA Damage In Chinese Hamster Lung Fibroblast V79 Cell Lines. AB - OBJECTIVE: Many studies have been published on the antioxidative effects of boric acid (BA) and sodium borates in in vitro studies. However, the boron (B) concentrations tested in these in vitro studies have not been selected by taking into account the realistic blood B concentrations in humans due to the lack of comprehensive epidemiological studies. The recently published epidemiological studies on B exposure conducted in China and Turkey provided blood B concentrations for both humans in daily life and workers under extreme exposure conditions in occupational setting. The results of these studies have made it possible to test antioxidative effects of BA in in vitro studies within the concentra- tion range relevant to humans. The aim of this study was to investigate the protective ef- fects of BA against oxidative DNA damage in V79 (Chinese hamster lung fibroblast) cells. The concentrations of BA tested for its protective effect was selected by taking the blood B concentrations into account reported in previously published epidemiological studies. Therefore, the concentrations of BA tested in this study represent the exposure levels for humans in both daily life and occupational settings. MATERIALS AND METHODS: In this experimental study, comet assay and neutral red uptake (NRU) assay methods were used to determinacy to toxicity and genotoxicity of BA and hydrogen peroxide (H2O2). RESULTS: The results of the NRU assay showed that BA was not cytotoxic within the tested concentrations (3, 10, 30, 100 and 200 uM). These non-cytotoxic concentrations were used for comet assay. BA pre-treatment significantly reduced (P<0.05, one-way ANOVA) the DNA damaging capacity of H2O2 at each tested BA concentrations in V79 cells. CONCLUSION: Consequently, pre-incubation of V79 cells with BA has significantly reduced the H2O2-induced oxidative DNA damage in V79 cells. The protective effect of BA against oxidative DNA damage in V79 cells at 5, 10, 50, 100 and 200 MUM (54, 108, 540, 1080, and 2161 ng/ml B equivalents) concentrations was proved in this in vitro study. PMID- 26862535 TI - Comments on: Effects of Wi-Fi (2.45 GHz) Exposure on Apoptosis, Sperm Parameters and Testicular Histomorphometry in Rats: A Time Course Study. PMID- 26862533 TI - Protective Effect of Selenium-Based Medicines on Toxicity of Three Common Organophosphorus Compounds in Human Erythrocytes In Vitro. AB - OBJECTIVE: Organophosphorus (OP) compounds are used to control pests, however they can reach the food chain and enter the human body causing serious health problems by means of acetylcholinesterase (AChE) inhibition and oxidative stress (OS). Among the OPs, chlorpyrifos (CHP), malathion (MAL), and diazinon (DIA) are commonly used for commercial extermination purposes, in addition to veterinary practices, domestic, agricul- ture and public health applications. Two new recently registered medicines that contain selenium and other antioxidants, IMOD and angipars (ANG), have shown beneficial ef- fects for OS related disorders. This study examines the effect of selenium-based medi- cines on toxicity of three common OP compounds in erythrocytes. MATERIALS AND METHODS: In the present experimental study, we determined the ef- ficacy of IMOD and ANG on OS induced by three mentioned OP pesticides in human erythrocytes in vitro. After dose-response studies, AChE, lipid peroxidation (LPO), total antioxidant power (TAP) and total thiol molecules (TTM) were measured in eryth- rocytes after exposure to OPs alone and in combined treatment with IMOD or ANG. RESULTS: AChE activity, TAP and TTM reduced in erythrocytes exposed to CHP, MAL and DIA while they were restored in the presence of ANG and IMOD. ANG and IMOD reduced the OPs-induced elevation of LPO. CONCLUSION: The present study shows the positive effects of IMOD and ANG in re- duction of OS and restoration of AChE inhibition induced by CHP, MAL and DIA in erythrocytes in vitro. PMID- 26862536 TI - Comments on: Association Study between Coronary Artery Disease and rs1333049 and rs10757274 Polymorphisms at 9p21 Locus in South-West Iran. PMID- 26862537 TI - Beach Soccer Injuries During the Japanese National Championships. AB - BACKGROUND: The frequency and severity of injury in beach soccer are unknown. PURPOSE: To estimate the incidence rates, characteristics, and risk factors for injuries associated with beach soccer. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: The same sports physician examined and recorded injuries incurred during the Japanese National Beach Soccer Championships in 2013 and 2014. Posttournament follow-up was made for all injuries. Match exposure for each player was recorded through video review to examine individual risk factors. RESULTS: A total of 58 injuries were recorded during 54 matches. The overall injury rate was 179.0 (95% CI, 138.4-231.6), and the time-loss injury rate was 28.2 (95% CI, 14.7-54.1) per 1000 player-hours. The foot/toe (34.9%) was the most frequently injured area, followed by the lower leg (22.2%) and thigh (11.1%). There was only 1 ankle injury (1.6%). The most frequent injury type was contusions (60.3%), followed by lacerations/abrasions (14.3%) and sprains/ligament injuries (6.3%). Only 4 injuries resulted in >=30 days of time loss (7.4%). After adjusting for age, a previous history of severe injury and longer experience of beach soccer were significantly associated with injury risk. CONCLUSION: The time-loss injury rate in this study was comparable to the rates reported during the matches of soccer or futsal tournaments. However, a greater incidence of foot/toe injury and lacerations/abrasions as well as a lower incidence of ankle injury distinguished beach soccer from soccer and futsal, possibly related to the specific playing conditions of being barefoot on a sand surface. PMID- 26862538 TI - Ulnar Collateral Ligament Reconstruction: The Rush Experience. AB - BACKGROUND: Ulnar collateral ligament reconstruction (UCLR) is a common surgery performed in professional, collegiate, and high school athletes. PURPOSE: To report patient demographics, surgical techniques, and outcomes of all UCLRs performed at a single institution from 2004 to 2014. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: All patients who underwent UCLR from January 1, 2004, through December 31, 2014, at a single institution were identified. Charts were reviewed to determine patient age, sex, date of surgery, sport played, athletic level, surgical technique, graft type, and complications. Data were collected prospectively, and patients were contacted via phone calls to obtain the return-to-sport rate, Conway-Jobe score, Andrews-Timmerman score, and Kerlan Jobe Orthopaedic Clinic (KJOC) Shoulder and Elbow score. Continuous variable data were reported as weighted means, and categorical variable data were reported as frequencies with percentages. RESULTS: A total of 187 patients (188 elbows) underwent UCLR during the study period (92% male; mean age, 19.6 +/- 4.7 years; 78.2% right elbows). There were 165 baseball players (87.8% of all patients), 155 of whom were pitchers (82.5% of all patients). Ninety-seven (51.6%) were college athletes, 68 (36.2%) high school athletes, and 7 (3.7%) professional athletes at the time of surgery. The docking technique was used in 110 (58.5%) patients while the double-docking technique was used in 78 (41.5%). An ipsilateral palmaris longus graft was used in 110 (58.5%) patients while a hamstring autograft was used in 48 (25.5%) patients. The ulnar nerve was subcutaneously transposed in 79 (42%) patients. Clinical follow-up data were available on 85 patients. Mean follow-up was 60 +/- 30.8 months. Overall, 94.1% of patients were able to return to sport and had a Conway-Jobe score of good/excellent while 4.3% had a score of fair. The mean KJOC score was 90.4 +/- 6.7 and mean Andrews-Timmerman score was 92.5 +/- 7.1. Subsequent surgeries were performed in 5.3% of patients. CONCLUSION: UCLR was performed most commonly on collegiate athletes using an ipsilateral palmaris longus graft. Overall, 94.1% of patients who underwent UCLR were able to return to sport with a mean KJOC score of 90.4 and Andrews-Timmerman Score of 92.5. PMID- 26862540 TI - Comment on: Dietary yeast reduce inflammation in central nerve system via microflora. PMID- 26862541 TI - Reply to comment on: Dietary yeasts reduce inflammation in central nervous system via microflora. PMID- 26862542 TI - Screening Performance Characteristic of Ultrasonography and Radiography in Detection of Pleural Effusion; a Meta-Analysis. AB - INTRODUCTION: The role of ultrasonography in detection of pleural effusion has long been a subject of interest but controversial results have been reported. Accordingly, this study aims to conduct a systematic review of the available literature on diagnostic value of ultrasonography and radiography in detection of pleural effusion through a meta-analytic approach. METHODS: An extended search was done in databases of Medline, EMBASE, ISI Web of Knowledge, Scopus, Cochrane Library, and ProQuest. Two reviewers independently extracted the data and assessed the quality of the articles. Meta-analysis was performed using a mixed effects binary regression model. Finally, subgroup analysis was carried out in order to find the sources of heterogeneity between the included studies. RESULTS: 12 studies were included in this meta-analysis (1554 subjects, 58.6% male). Pooled sensitivity of ultrasonography in detection of pleural effusion was 0.94 (95% CI: 0.88-0.97; I2= 84.23, p<0.001) and its pooled specificity was calculated to be 0.98 (95% CI: 0.92-1.0; I2= 88.65, p<0.001), while sensitivity and specificity of chest radiography were 0.51 (95% CI: 0.33-0.68; I2= 91.76, p<0.001) and 0.91 (95% CI: 0.68-0.98; I2= 92.86, p<0.001), respectively. Sensitivity of ultrasonography was found to be higher when the procedure was carried out by an intensivist or a radiologist using 5-10 MHz transducers. CONCLUSION: Chest ultrasonography, as a screening tool, has a higher diagnostic accuracy in identification of plural effusion compared to radiography. The sensitivity of this imaging modality was found to be higher when performed by a radiologist or an intensivist and using 5-10MHz probes. PMID- 26862543 TI - The Accuracy of Urinalysis in Predicting Intra-Abdominal Injury Following Blunt Traumas. AB - INTRODUCTION: In cases of blunt abdominal traumas, predicting the possible intra abdominal injuries is still a challenge for the physicians involved with these patients. Therefore, this study was designed, to evaluate the accuracy of urinalysis in predicting intra-abdominal injuries. METHODS: Patients aged 15 to 65 years with blunt abdominal trauma who were admitted to emergency departments were enrolled. Abdominopelvic computed tomography (CT) scan with intravenous contrast and urinalysis were requested for all the included patients. Demographic data, trauma mechanism, the results of urinalysis, and the results of abdominopelvic CT scan were gathered. Finally, the correlation between the results of abdominopelvic CT scan, and urinalysis was determined. Urinalysis was considered positive in case of at least one positive value in gross appearance, blood in dipstick, or red blood cell count. RESULTS: 325 patients with blunt abdominal trauma were admitted to the emergency departments (83% male with the mean age of 32.63+/-17.48 years). Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios of urinalysis, were 77.9% (95% CI: 69.6-84.4), 58.5% (95% CI: 51.2-65.5), 56% (95% CI: 48.5 63.3), 79.6% (95% CI: 71.8-85.7), 1.27% (95% CI: 1.30-1.57), and 0.25% (95% CI: 0.18-0.36), respectively. CONCLUSION: The diagnostic value of urinalysis in prediction of blunt traumatic intra-abdominal injuries is low and it seems that it should be considered as an adjuvant diagnostic tool, in conjunction with other sources such as clinical findings and imaging. PMID- 26862544 TI - Knowledge and Attitude of Iranian Red Crescent Society Volunteers in Dealing with Bioterrorist attacks. AB - INTRODUCTION: Bioterrorism is a worldwide problem and has been the focus of attention during recent decades. There is no precise information on the knowledge, attitude, and preparedness of Iranian Red Crescent volunteers in dealing with bioterrorism. Therefore, the present study aimed to evaluate the above-mentioned parameters in Mahabad Red Crescent Society volunteers. METHODS: In this prospective cross-sectional study, the knowledge of 120 volunteers was evaluated and rated as poor, moderate, and good. In addition, attitude of the volunteers and preparedness of Mahabad Red Crescent Society was rated as inappropriate and appropriate using a questionnaire. RESULTS: The mean age of volunteers was 32.0 +/- 8.2 years (62.5% male). 2 (1.7%) volunteers had good knowledge while 94 (78.3%) had no knowledge regarding bioterrorist attack management. Only 1 (0.8%) volunteer had appropriate attitude and 6 (5.0%) stated their preparedness for being sent out to the crisis zone. 116 volunteers (96.7%) indicated that Mahabad Red Crescent Society has an inappropriate level of preparedness to encounter bioterrorist attacks. CONCLUSION: The findings of the present study showed poor knowledge and inappropriate attitude of Mahabad Red Crescent Society volunteers in encountering probable bioterrorist attacks. Furthermore, the Red Crescent Society of this town had an inappropriate level of preparedness in the field of bioterrorism from the viewpoint of the studied volunteers. PMID- 26862545 TI - An Epidemiologic Study of Pediatric Poisoning; a Six-month Cross-sectional Study. AB - INTRODUCTION: Intentional and unintentional poisoning are among the most common reasons for referrals to emergency department (ED). Therefore, the present study was designed to evaluate epidemiologic features and effective risk factors of intentional and unintentional poisoning in children. METHODS: This prospective cross-sectional study was carried out in ED of Loghman Hakim Hospital, greatest referral poison center of Iran, Tehran during March to August 2014. Demographic data, medical history, history of psychiatric disease in child, the cause of poisoning, parents' educational level, household monthly income, location of residence, history of addiction or divorce in family, and the poisoning intentionality were gathered. Data were analyzed using SPSS 18 and appropriate statistical tests based on the purpose of study. RESULTS: 414 participants with the mean age of 4.2 +/- 3.43 years were included (57.5% male). Children in the 0 4 year(s) age range had the most frequency with 281 (67.9%) cases. 29 (7%) cases were intentional (62% female, 76% in the 10-14 years old group). Methadone with 123 (29.7%) cases was the most frequent toxic agent in general and in unintentional cases. 10-14 years of age (p = 0.001), and the history of psychiatric disease in children (p <0.001), had a direct correlation with probability of intentional poisoning. While, history of addiction in the family showed an indirect correlation with this probability (p = 0.045). CONCLUSION: Based on the results of this study, most cases of poisoning in the children were unintentional methadone intoxication in boys in the 0-4 age range with a history of a psychiatric disease, and those who had a history of addiction in the family. In addition, the most powerful risk factor for the children's intentional poisoning was their history of psychiatric disease. The history of addiction in the child's family had indirect correlation with intentional intoxications. PMID- 26862546 TI - True Vertigo Patients in Emergency Department; an Epidemiologic Study. AB - INTRODUCTION: Vertigo prevalence is estimated to be 1.8% among young adults and more than 30% in the elderly. 13-38% of the referrals of patients over 65 years old in America are due to vertigo. Vertigo does not increase the risk of mortality but it can affect the patient's quality of life. Therefore, this study was designed to evaluate the epidemiologic characteristics of vertigo patients referred to the emergency department (ED). METHODS: In this 6-month retrospective cross-sectional study, the profiles of all vertigo patients referred to the ED of Imam Hossein Hospital, Tehran, Iran, from October 2013 to March 2014 were evaluated. Demographic data and baseline characteristics of the patients were recorded and then patients were divided into central and peripheral vertigo. The correlation of history and clinical examination with vertigo type was evaluated and screening performance characteristics of history and clinical examination in differentiating central and peripheral vertigo were determined. RESULTS: 379 patients with the mean age of 50.69 +/- 11.94 years (minimum 18 and maximum 86) were enrolled (58.13% female). There was no sex difference in vertigo incidence (p = 0.756). A significant correlation existed between older age and increase in frequency of central cases (p < 0.001). No significant difference was detected between the treatment protocols regarding ED length of stay (p = 0.72). There was a significant overlap between the initial diagnosis and the final decision based on imaging and neurologist's final opinion (p < 0.001). In the end, 361 (95.3%) patients were discharged from ED, while 18 were disposed to the neurology ward. No case of mortality was reported. CONCLUSION: Sensitivity and specificity of history and clinical examination in differentiating central and peripheral vertigo were 99 (95% CI: 57-99) and 99 (95% CI: 97-99), respectively. PMID- 26862547 TI - Diagnostic Accuracy of Ultrasonography and Radiography in Initial Evaluation of Chest Trauma Patients. AB - INTRODUCTION: Application of chest radiography for all multiple trauma patients is associated with a significant increase in total costs, exposure to radiation, and overcrowding of the emergency department. Ultrasound has been introduced as an alternative diagnostic tool in this regard. The aim of the present study is to compare the diagnostic accuracy of chest ultrasonography and radiography in detection of traumatic intrathoracic injuries. METHODS: In the present prospective cross-sectional study, patients with traumatic intrathoracic injuries, who were referred to the emergency department from December 2013 to December 2014, were assessed. The patients underwent bedside ultrasound, radiographic and computed tomography (CT) scan examinations based on ATLS recommendations. Screening performance characteristics of ultrasonography and radiography were compared using SPSS 21.0. Chest CT scan was considered as gold standard. RESULTS: 152 chest trauma patients with a mean age of 31.4 +/- 13.8 years (range: 4 - 67), were enrolled (77.6% male). Chest CT scan showed pulmonary contusion in 48 (31.6%) patients, hemothorax in 29 (19.1%), and pneumothorax in 55 (36.2%) cases. Area under the ROC curve of ultrasonography in detection of pneumothorax, hemothorax, and pulmonary contusion were 0.91 (95% CI: 0.86-0.96), 0.86 (95% CI: 0.78-0.94), and 0.80 (95% CI: 0.736-0.88), respectively. Area under the ROC curve of radiography was 0.80 (95% CI: 0.736-0.87) for detection of pneumothorax, 0.77 (95% CI: 0.68-0.86) for hemothorax, and 0.58 (95% CI: 0.5 0.67) for pulmonary contusion. Comparison of areas under the ROC curve declared the significant superiority of ultrasonography in detection of pneumothorax (p = 0.02) and pulmonary contusion (p < 0.001). However, the diagnostic value of the two tests was equal in detection of hemothorax (p = 0.08). CONCLUSION: The results of the present study showed that ultrasonography is preferable to radiography in the initial evaluation of patients with traumatic injuries to the thoracic cavity. PMID- 26862548 TI - Patients' Attitude toward Breaking Bad News; a Brief Report. AB - INTRODUCTION: Delivering bad news is a stressful moment for both physicians and patients. The purpose of this investigation was to explore the patients' preferences and attitudes toward being informed about the bad news. METHODS: This cross-sectional study was done on patients admitted to Imam Khomeini Hospital, Sari, Iran, from September 2014 to February 2015. Patient attitude regarding breaking bad news was evaluated using a reliable and valid questionnaire. RESULTS: 130 patients were evaluated (61.5% male, mean age = 46.21 +/- 12.1 years). 118 (90.76%) participants believed that the patient himself/herself should be informed about the disease's condition. 120 (92.30%) preferred to hear the news from a skillful physician and 105 (80.76%) believed that emergency department is not a proper place for breaking bad news. CONCLUSION: Based on the results of the present study, most participants believed that the most experienced and skillful physician should inform them completely regarding their medical condition. At the same time they declared that, it is best to hear bad news in a calm and suitable place and time rather than emergency department or hospital corridors during teaching rounds. PMID- 26862549 TI - Urinary Retention and Air in the Spinal Canal; a Case Report. AB - Cauda equina syndrome (CES) although uncommon, is a very serious condition, which should be diagnosed as soon as possible. Urinary dysfunction following a lumbosacral trauma is a key for the physician to consider CES as the most probable diagnosis. Up to 62% of CES patients report a recent episode of trauma. We herein report a young man with CES due to sacral fracture with an interesting imaging. PMID- 26862550 TI - From Pulmonary Embolism to Inflammatory Bowel Disease; Give Tunnel Vision up. AB - Inflammatory bowel disease (IBD) is a multisystem disorder with gastrointestinal tract involvement. These patients have the higher risk for thromboembolic events compared to normal population. This report describes a unique case of pulmonary embolism as a first manifestation of inflammatory bowel disease. PMID- 26862551 TI - A 52-Year-Old Woman with a Palpable Abdominal Mass. PMID- 26862552 TI - Management of Deep Vein Thrombosis in Emergency Departments;Time to Change the Viewpoint. PMID- 26862553 TI - Evidence Based Emergency Medicine; Part 4: Pre-test and Post-test Probabilities and Fagan's nomogram. PMID- 26862554 TI - Coronary patients with high plasma omentin are at a higher cardiovascular risk. AB - The adipokine omentin, also known as intelectin, is a secretory protein, expressed in visceral adipose tissue and is highly abundant in plasma. It is involved in the development of chronic inflammatory diseases, but nothing is known about its impact on the cardiovascular event risk. Here, plasma omentin was measured in 295 patients undergoing coronary angiography for the evaluation of established or suspected stable coronary artery disease (CAD). Patients were separated according to the median plasma omentin concentrations into a high and low omentin group and cardiovascular events occurring during a period of 3.5 years have been recorded. We observed that patients within the high omentin group had significantly more cardiovascular events than patients in the low omentin group. This was true even if using different study endpoints. This article describes data related to a research article titled "High Plasma Omentin Predicts Cardiovascular Events Independently From the Presence and Extent of Angiographically Determined Atherosclerosis" (Saely et al., 2015) [1]. PMID- 26862555 TI - Lipidomic dataset of plasma from patients infected with wild type and nef deficient HIV-1 strain. AB - Previous in vitro and in vivo studies demonstrated that HIV protein nef plays a key role in impairing cellular and systemic cholesterol metabolism in HIV disease, but clinical support for these findings is lacking. Here we present the data of comparative lipidomic analysis (330 lipid species) of plasma samples from HIV-negative subjects, patients infected with WT HIV-1 strain and patients infected with nef-deficient strain of HIV-1. We determine which effects of HIV on plasma lipidome are explained by the presence of nef. The data can be used to evaluate cardiovascular risk in HIV disease and to assess the role of nef in HIV induced disturbances in systemic lipid metabolism. The full impact of nef deficiency on lipid and lipoprotein metabolism in HIV-infected patients is presented in the accompanying study "Lipid Metabolism in Patients Infected with Nef-deficient HIV-1 Strain" [1]. PMID- 26862556 TI - Spectral data of specular reflectance, narrow-angle transmittance and angle resolved surface scattering of materials for solar concentrators. AB - The spectral specular reflectance of conventional and novel reflective materials for solar concentrators is measured with an acceptance angle of 17.5 mrad over the wavelength range 300-2500 nm at incidence angles 15-60 degrees using a spectroscopic goniometry system. The same experimental setup is used to determine the spectral narrow-angle transmittance of semi-transparent materials for solar collector covers at incidence angles 0-60 degrees . In addition, the angle resolved surface scattering of reflective materials is recorded by an area-scan CCD detector over the spectral range 350-1050 nm. A comprehensive summary, discussion, and interpretation of the results are included in the associated research article "Spectral reflectance, transmittance, and angular scattering of materials for solar concentrators" in Solar Energy Materials and Solar Cells. PMID- 26862557 TI - Experimental data regarding the characterization of the flame behavior near lean blowout in a non-premixed liquid fuel burner. AB - The article presents the data related to the flame acquisitions in a liquid-fuel gas turbine derived burner operating in non-premixed mode under three different equivalence fuel/air ratio, which corresponds to a richer, an intermediate, and an ultra-lean condition, near lean blowout (LBO). The data were collected with two high speed visualization systems which acquired in the visible (VIS) and in the infrared (NIR) spectral region. Furthermore chemiluminescence measurements, which have been performed with a photomultiplier (PMT), equipped with an OH* filter, and gas exhaust measurements were also given. For each acquisition the data were related to operating parameters as pressure, temperature and equivalent fuel/air ratio. The data are related to the research article "Image processing for the characterization of flame stability in a non-premixed liquid fuel burner near lean blowout" in Aerospace Science and Technology [1]. PMID- 26862559 TI - Data from comprehensive analysis of nuclear localization signals. AB - This article describes data related to a research article titled "Comprehensive analysis of the dynamic structure of nuclear localization signals" by Yamagishi et al. [1]. In this article, we provide the data covering wider range of the mammalian NLSs in UniProt (Universal Protein Resource) [2] regardless of their conformations. To be more specific as follows: We have extracted all NLSs which are clearly indicated as "NLS" with evidence type (a code from the Evidence Codes Ontology) [3] in UniProt. A total of 1364 NLSs in 1186 proteins were extracted from UniProt. The number of NLSs found in each protein (UniProt ID), the sequence length of NLSs and their distribution are shown. PMID- 26862558 TI - Data supporting the spectrophotometric method for the estimation of catalase activity. AB - Here we provide raw and processed data and methods for the estimation of catalase activities. The method for presenting a simple and accurate colorimetric assay for catalase activities is described. This method is based on the reaction of undecomposed hydrogen peroxide with ammonium molybdate to produce a yellowish color, which has a maximum absorbance at 374 nm. The method is characterized by adding a correction factor to exclude the interference that arises from the presence of amino acids and proteins in serum. The assay acts to keep out the interferences that arose from measurement of absorbance at unsuitable wavelengths. PMID- 26862560 TI - High frequency activation data used to validate localization of cortical electrodes during surgery for deep brain stimulation. AB - Movement related synchronization of high frequency activity (HFA, 76-100 Hz) is a somatotopic process with spectral power changes occurring during movement in the sensorimotor cortex (Miller et al., 2007) [1]. These features allowed movement related changes in HFA to be used to functionally validate the estimations of subdural electrode locations, which may be placed temporarily for research in deep brain stimulation surgery, using the novel tool described in Randazzo et al. (2015) [2]. We recorded electrocorticography (ECoG) signals and localized electrodes in the region of the sensorimotor cortex during an externally cued hand grip task in 8 subjects. Movement related HFA was determined for each trial by comparing HFA spectral power during movement epochs to pre-movement baseline epochs. Significant movement related HFA was found to be focal in time and space, occurring only during movement and only in a subset of electrodes localized to the pre- and post-central gyri near the hand knob. To further demonstrate the use of movement related HFA to aid electrode localization, we provide a sample of the electrode localization tool, with data loaded to allow readers to map movement related HFA onto the cortical surface of a sample patient. PMID- 26862561 TI - Curated eutherian third party data gene data sets. AB - The free available eutherian genomic sequence data sets advanced scientific field of genomics. Of note, future revisions of gene data sets were expected, due to incompleteness of public eutherian genomic sequence assemblies and potential genomic sequence errors. The eutherian comparative genomic analysis protocol was proposed as guidance in protection against potential genomic sequence errors in public eutherian genomic sequences. The protocol was applicable in updates of 7 major eutherian gene data sets, including 812 complete coding sequences deposited in European Nucleotide Archive as curated third party data gene data sets. PMID- 26862562 TI - Callus cell proliferation from broccoli leaf slice using IBA and BAP in vitro culture: Its biochemical and antioxidant properties. AB - Plant tissue or cell culture keeps a significant role in micro-propagation in the plant production industry. Combination of 6-Benzylaminopurine (BAP) and other plant growth regulators like 1-Naphthaleneacetic acid (NAA) or Indole-3-acetic acid (IAA) or indole-3-butyric acid (IBA) was used in the most of the research in tissue culture. The study was carried out to investigate the optimization of the concentration of IBA and BAP combination (0, 0.25, 0.50, 1.0, 1.50, 2.0, 2.5, 3.0 and 3.5 mg/l) for the root, callus and leaf proliferation from the leaf cutting slice. The highest number (6.75) of root proliferation was observed in the concentration of 2.0 mg/l IBA+0.25 mg/l BAP combination. The callus initiation was found in the concentration of IBA 1.0-3.5 mg/l+BAP 1.0-2.0 mg/l. However, the highest callus weight was observed at the concentration of IBA 1.5 mg/l+BAP 1.0 mg/l combination than other combination of concentrations. Positively leaf initiation and formation was better in the concentration of IBA 1-3.5 mg/l+BAP 1.0-2.0 mg/l combination. In addition, the 2,2-diphenyl-2-picrylhydarzyl (DPPH) free radical scavenging potential was higher (70.1%) in leaves extract than in callus extracts (46.3%) at the concentration of 10 mg/ml though both extracts had lower DPPH free radical scavenging activity compared to the positive control, vitamin C and BHT. Theresults conclude that the optimum concentration was IBA 1.5 mg/l+BAP 1.0 mg/l combination to produce callus cell proliferation and concentration of 2.0 mg/l IBA+0.25 mg/l BAP combination was the optimum for root proliferation of broccoli in vitro. PMID- 26862563 TI - Data on bone marrow stem cells delivery using porous polymer scaffold. AB - Low bioavailability and/or survival at the injury site of transplanted stem cells necessitate its delivery using a biocompatible, biodegradable cell delivery vehicle. In this dataset, we report the application of a porous biocompatible, biodegradable polymer network that successfully delivers bone marrow stem cells (BMSCs) at the wound site of a murine excisional splint wound model. In this data article, we are providing the additional data of the reference article "Porous polymer scaffold for on-site delivery of stem cells - protects from oxidative stress and potentiates wound tissue repair" (Ramasatyaveni et al., 2016) [1]. This data consists of the characterization of bone marrow stem cells (BMSCs) showing the pluripotency and stem cell-specific surface markers. Image analysis of the cellular penetration into PEG-PU polymer network and the mechanism via enzymatic activation of MMP-2 and MMP-13 are reported. In addition, we provide a comparison of various routes of transplantation-mediated BMSCs engraftment in the murine model using bone marrow transplantation chimeras. Furthermore, we included in this dataset the engraftment of BMSCs expressing Sca-1(+)Lin( )CD133(+)CD90.2(+) in post-surgery day 10. PMID- 26862564 TI - Genetic characterization of inbred lines of Chinese cabbage by DNA markers; towards the application of DNA markers to breeding of F1 hybrid cultivars. AB - Chinese cabbage (Brassica rapa L. var. pekinensis) is an important vegetable in Asia, and most Japanese commercial cultivars of Chinese cabbage use an F1 hybrid seed production system. Self-incompatibility is successfully used for the production of F1 hybrid seeds in B. rapa vegetables to avoid contamination by non hybrid seeds, and the strength of self-incompatibility is important for harvesting a highly pure F1 seeds. Prediction of agronomically important traits such as disease resistance based on DNA markers is useful. In this dataset, we identified the S haplotypes by DNA markers and evaluated the strength of self incompatibility in Chinese cabbage inbred lines. The data described the predicted disease resistance to Fusarium yellows or clubroot in 22 Chinese cabbage inbred lines using gene associated or gene linked DNA markers. PMID- 26862566 TI - NOE distance and dihedral angle restraints to calculate the solution structure of the NDH-1 complex subunit CupS from Thermosynechococcus elongatus. AB - Here, we have compiled a nuclear magnetic resonance (NMR)-derived set of nuclear Overhauser enhancement (NOE) distance and dihedral angle restraints that allow for the calculation of the structure of the NDH-1 complex subunit CupS from Thermosynechococcus elongatus in solution. These restraints to calculate the structure in solution of CupS have been deposited to the Protein Data Bank (www.rcsb.org) under PDB-ID accession number 2MXA. This is the first experimental data set published to compute the three-dimensional structure of CupS. This structure is presented in the research article "Solution structure of the NDH-1 complex subunit CupS from Thermosynechococcus elongatus" published by Korste et al. in Biochim. Biophys. Acta 1847(2015)1212-1219 [1]. The cyanobacterial multi subunit membrane protein complex NDH-1 structurally and functionally relates to Complex I of eubacteria and mitochondria. The NDH-1 complex is mechanistically involved in respiration and cyclic electron transfer around photosystem I (PSI) as well as in a unique mechanism for inorganic carbon concentration. PMID- 26862565 TI - Time-course investigation of Phytophthora infestans infection of potato leaf from three cultivars by quantitative proteomics. AB - Potato late blight is one the most important crop diseases worldwide. Even though potato has been studied for many years, the potato disease late blight still has a vast negative effect on the potato production [1], [2], [3]. Late blight is caused by the pathogen Phytophthora infestans (P. infestans), which initiates infection through leaves. However, the biological activities during different stages of infection are poorly described, and could enable novel or improved ways of defeating late blight infection [4]. Therefore, we investigated the interactions between P. infestans (mixed strain culture) and potato (Solanum tuberosum). Three commercially available field potato cultivars of different resistance to late blight infection; Kuras (moderate), Sarpo Mira (highly resistant) and Bintje (very susceptable) were grown under controlled green house conditions and inoculated with a diversity of P. infestans populations. We used label-free quantitative proteomics to investigate the infection with P. infestans in a time-course study over 258 h. Several key issues limits proteome analysis of potato leaf tissue [5], [6], [7]. Firstly, the immense complexity of the plant proteome, which is further complicated by the presence of highly abundant proteins, such as ribulose bisphosphate carboxylase/oxygenase (RuBisCO). Secondly, plant leaf and potato, in particular, contain abundant levels amounts of phenols and polyphenols, which hinder or completely prevent a successful protein extraction. Hitherto, protein profiling of potato leaf tissues have been limited to few proteome studies and only 1484 proteins have been extracted and comprehensively described [5], [8], [9]. We here present the detailed methods and raw data by optimized gel-enhanced label free quantitative approach. The methodology enabled us to detect and quantify between 3248 and 3529 unique proteins from each cultivar, and up to 758 P. infestans derived proteins. The complete dataset is available via ProteomeXchange, with the identifier PXD002767. PMID- 26862567 TI - Epithelial sodium channels (ENaC) produce extracellular positive DC potentials in the retinal neuroepithelium. AB - Positive DC (direct current) potentials were measured in the extracellular space in the retinal neuroepithelium of chick embryos. The positive DC potential was suppressed by amiloride, a blocker for epithelial Na(+) channels (ENaC). Amiloride also decreased the resistance of the extracellular space as measured by passing a constant current through a microelectrode. The positive DC potential is necessary for the guidance of retinal ganglion cell axons [1]. PMID- 26862568 TI - Top-down characterization data on the speciation of the Candida albicans immunome in candidemia. AB - The characterization of pathogen-specific antigenic proteins at the protein species level is crucial in the development and molecular optimization of novel immunodiagnostics, vaccines or immunotherapeutics for infectious diseases. The major requirements to achieve this molecular level are to obtain 100% sequence coverage and identify all post-translational modifications of each antigenic protein species. In this article, we show nearly complete sequence information for five discrete antigenic species of Candida albicans Tdh3 (glyceraldehyde-3 phosphate dehydrogenase), which have been reported to be differentially recognized both among candidemia patients and between candidemia and control patients. A comprehensive description of the top-down immunoproteomic strategy used for seroprofiling at the C. albicans protein species level in candidemia as well as for the chemical characterization of this immunogenic protein (based on high-resolution 2-DE, Western blotting, peptide mass fingerprinting, tandem mass spectrometry and de novo peptide sequencing) is also provided. The top-down characterization data on the speciation of the C. albicans immunome in candidemia presented here are related to our research article entitled "Seroprofiling at the Candida albicans protein species level unveils an accurate molecular discriminator for candidemia" (Pitarch et al., J. Proteomics, 2015, http://dx.doi.org/10.1016/j.jprot.2015.10.022). PMID- 26862569 TI - Data for induction of cytotoxic response by natural and novel quercetin glycosides. AB - The flavonoids quercetin, and its natural glycosides isoquercetin and rutin, are phytochemicals commonly consumed in plant-derived foods and used as a food beverage additive. Semi-synthetic maltooligosyl isoquercetin, monoglucosyl rutin and maltooligosyl rutin were developed by synthetic glycosylation to improve their water solubility for food and other applications. Using a system of Chinese hamster ovary (CHO) cells, this study examined the differences in cytotoxic responses induced by short and continuous exposure of natural and synthetic flavonoids. By assessing cell viability after short term exposure and clonogenicity with continuous exposure under various flavonoids, quercetin aglycone is confirmed to be the most cytotoxic flavonoids, and heavily glucosylated maltooligosyl rutin was the least cytotoxic. The other heavily glucosylated maltooligosyl isoquercetin showed intermediate cytotoxicity and similar toxicity as isoquercetin. PMID- 26862570 TI - Frequent detection of CXCR4-using viruses among Brazilian blood donors with HIV-1 long-standing infection and unknown clinical stage: Analysis of massive parallel sequencing data. AB - The determination of viral tropism is critically important and highly recommended to guide therapy with the CCR5 antagonist, which does not inhibit the effect of X4-tropic viruses. Here, we report the prevalence of HIV-1*4 HIV strains in 84 proviral DNA massively parallel sequencing "MPS" data from well-defined non recently infected first-time Brazilian blood donors. The MPS data covering the entire V3 region of the env gene was extracted from our recently generated HIV-1 genomes sequenced by a paired-end protocol (Illumina). Of the 84 MPS data samples, 63 (75%) were derived from donors with long-standing infection and 21 (25%) were lacking stage information. HIV-1 tropism was inferred using Geno2pheno (g2p) [454] algorithm (FPR=1%, 2.5%, and 3.75%). Among the 84 data samples for which tropism was defined by g2p2.5%, 13 (15.5%) participants had detectable CXCR4-using viruses in their MPS reads. Mixed infections with R5 and X4 were observed in 11.9% of the study subjects and minority X4 viruses were detected in 7 (8.3%) of participants. Nine of the 63 (14.3%) subjects with LS infection were predicted by g2p 2.5% to harbor proviral CXCR4-using viruses. Our findings of a high proportion of blood donors (15.5%) harboring CXCR4-using viruses in PBMCs may indicate that this phenomenon is common. These findings may have implications for clinical and therapeutic aspects and may benefit individuals who plan to receive CCR5 antagonists. PMID- 26862571 TI - Annotated compound data for modulators of detergent-solubilised or lipid reconstituted respiratory type II NADH dehydrogenase activity obtained by compound library screening. AB - The energy-generating membrane protein NADH dehydrogenase (NDH-2), a proposed antibacterial drug target (see "Inhibitors of type II NADH:menaquinone oxidoreductase represent a class of antitubercular drugs" Weinstein et al. 2005 [1]), was screened for modulators of activity in either detergent-solublised or lipid reconstituted (proteolipsome) form. Here we present an annotated list of compounds identified in a small-scale screen against NDH-2. The dataset contains information regarding the libraries screened, the identities of hit compounds and the physicochemical properties governing solubility and permeability. The implications of these data for future antibiotic discovery are discussed in our associated report, "Comparison of lipid and detergent enzyme environments for identifying inhibitors of membrane-bound energy-transducing proteins" [2]. PMID- 26862572 TI - Data for constructing insect genome content matrices for phylogenetic analysis and functional annotation. AB - Twenty one fully sequenced and well annotated insect genomes were used to construct genome content matrices for phylogenetic analysis and functional annotation of insect genomes. To examine the role of e-value cutoff in ortholog determination we used scaled e-value cutoffs and a single linkage clustering approach.. The present communication includes (1) a list of the genomes used to construct the genome content phylogenetic matrices, (2) a nexus file with the data matrices used in phylogenetic analysis, (3) a nexus file with the Newick trees generated by phylogenetic analysis, (4) an excel file listing the Core (CORE) genes and Unique (UNI) genes found in five insect groups, and (5) a figure showing a plot of consistency index (CI) versus percent of unannotated genes that are apomorphies in the data set for gene losses and gains and bar plots of gains and losses for four consistency index (CI) cutoffs. PMID- 26862573 TI - Data set from a comprehensive phosphoproteomic analysis of rice variety IRBB5 in response to bacterial blight. AB - Bacterial blight (BB) caused by Xanthomonas oryzae pv. oryzae (Xoo) has become one of the most devastating diseases for rice, a major food source for over half of the world populations. To investigate the roles of protein phosphorylation in rice bacterial blight resistance, a quantitative phosphoproteomic study was conducted in rice variety IRBB5 at 0 h and 24 h after Xoo infection. 2367 and 2223 phosphosites on 1334 and 1297 representative proteins were identified in 0 h and 24 h after Xoo infection, respectively, out of which 762 proteins were found to be differentially phosphorylated. In associated with the published article "A comprehensive quantitative phosphoproteome analysis of rice in response to bacterial blight" in BMC Plant Biology (Hou et al., 2015) [1], this dataset article provided the detailed information of experimental designing, methods, features as well as the raw data of mass spectrometry (MS) identification. The MS proteomics data could be fully accessed from the ProteomeXchange Consortium with the dataset identifier PXD002222. PMID- 26862574 TI - Spiked proteomic standard dataset for testing label-free quantitative software and statistical methods. AB - This data article describes a controlled, spiked proteomic dataset for which the "ground truth" of variant proteins is known. It is based on the LC-MS analysis of samples composed of a fixed background of yeast lysate and different spiked amounts of the UPS1 mixture of 48 recombinant proteins. It can be used to objectively evaluate bioinformatic pipelines for label-free quantitative analysis, and their ability to detect variant proteins with good sensitivity and low false discovery rate in large-scale proteomic studies. More specifically, it can be useful for tuning software tools parameters, but also testing new algorithms for label-free quantitative analysis, or for evaluation of downstream statistical methods. The raw MS files can be downloaded from ProteomeXchange with identifier PXD001819. Starting from some raw files of this dataset, we also provide here some processed data obtained through various bioinformatics tools (including MaxQuant, Skyline, MFPaQ, IRMa-hEIDI and Scaffold) in different workflows, to exemplify the use of such data in the context of software benchmarking, as discussed in details in the accompanying manuscript [1]. The experimental design used here for data processing takes advantage of the different spike levels introduced in the samples composing the dataset, and processed data are merged in a single file to facilitate the evaluation and illustration of software tools results for the detection of variant proteins with different absolute expression levels and fold change values. PMID- 26862575 TI - Data supporting that miR-92a suppresses angiogenic activity of adipose-derived mesenchymal stromal cells by down-regulating hepatocyte growth factor. AB - This article contains the full list of miRNAs expressed in cultured mesenchymal stromal cells, which were isolated from human adipose tissue. We provide here data regarding the effect of miR-92a overexpression on MSCs viability and cellular content of HGF and angiopoietin-1. These are followed by the data regarding the effect of conditioned medium of MSC transfected with pre-miR-92a, anti-miR-92a or scramble oligos on HUVEC viability as well as their tube formation efficiency. We also demonstrate here data regarding the effect of extracellular vesicle depletion from MSCs conditioned medium on its ability to stimulate the tube formation by HUVEC. Data interpretation and discussion can be found in Kalinina et al. (2015) [1]. PMID- 26862576 TI - Data on intracellular localization of RPSA upon alteration of its redox state. AB - Ribosomal Protein SA (RPSA), a component of the 40S ribosomal subunit, was identified as a H2O2 target in HeLa cells [1]. In order to analyze the intracellular localization of RPSA in different redox states we overexpressed wild-type RPSA (RPSAwt) or RPSA containing two cysteine to serine residue substitutions at positions 148 and 163 (RPSAmut) in HeLa cells. The transfected cells were exposed to H2O2 or N-acetylcysteine (NAC) and RPSA subcellular localization was assessed by immunofluorescence in permeabilized cells. In addition, co-immunofluorescence for RPSA and Ribosomal Protein S6 (RPS6) was performed in cells overexpressing RPSAwt or RPSAmut. Finally, the ribosomal expression of endogenous RPSA in the presence or absence of H2O2 was analyzed by Western blot. The data presented in this work is related to the research article entitled "Hydrogen peroxide regulates cell adhesion through the redox sensor RPSA" [1]. PMID- 26862577 TI - Dataset of producing and curing concrete using domestic treated wastewater. AB - We tested the setting time of cement, slump and compressive and tensile strength of 54 triplicate cubic samples and 9 cylindrical samples of concrete with and without a Super plasticizer admixture. We produced concrete samples made with drinking water and treated domestic wastewater containing 300, 400 kg/m(3) of cement before chlorination and then cured concrete samples made with drinking water and treated wastewater. Second, concrete samples made with 350 kg/m(3) of cement with a Superplasticizer admixture made with drinking water and treated wastewater and then cured with treated wastewater. The compressive strength of all the concrete samples made with treated wastewater had a high coefficient of determination with the control concrete samples. A 28-day tensile strength of all the samples was 96-100% of the tensile strength of the control samples and the setting time was reduced by 30 min which was consistent with a ASTMC191 standard. All samples produced and cured with treated waste water did not have a significant effect on water absorption, slump and surface electrical resistivity tests. However, compressive strength at 21 days of concrete samples using 300 kg/m(3) of cement in rapid freezing and thawing conditions was about 11% lower than concrete samples made with drinking water. PMID- 26862578 TI - Adjustments to the preanalytical phase of quantitative cell-free DNA analysis. AB - Evaluating the kinetics of cell-free DNA (cfDNA) in the blood of cancer patients could be a strong auxiliary component to the molecular characterization of cfDNA, but its potential clinical significance is obscured by the absence of an analytical consensus. To utilize quantitative cfDNA assessment with confidence, it is crucial that the preanalytical phase is standardized. In a previous publication, several preanalytical variables that may affect quantitative measurements of cfDNA were identified, and the most confounding variables were assessed further using the growth medium of cultured cancer cells as a source of cfDNA ("Cell-free DNA: Preanalytical variables" [1]). The data accompanying this report relates to these experiments, which includes numerous changes to the sample handling and isolation protocols, and can be used for the interpretation of these results and other similar experiments by different researchers. PMID- 26862580 TI - Data for spatial characterization of AC signal propagation over primary neuron dendrites. AB - Action potentials generated near the soma propagate not only into the axonal nerve connecting to the adjacent neurons but also into the dendrites interacting with a diversity of synaptic inputs as well as voltage gated ion channels. Measuring voltage attenuation factors between the soma and all single points of the dendrites in the anatomically reconstructed primary neurons with the same cable properties, we report the signal propagation data showing how the alternating current (AC) signal such as action potentials back-propagates over the dendrites among different types of primary neurons. Fitting equations and their parameter values for the data are also presented to quantitatively capture the spatial profile of AC signal propagation from the soma to the dendrites in primary neurons. Our data is supplemental to our original study for the dependency of dendritic signal propagation and excitability, and their relationship on the cell type-specific structure in primary neurons (DOI: 10.1016/j.neulet.2015.10.017 [1]). PMID- 26862579 TI - Data in support of alpha1beta1 and integrin-linked kinase interact and modulate angiotensin II effects in vascular smooth muscle cells. AB - The data provides information in support of the research article Moraes et al., Atherosclerosis 243(2) (2015) 477-485 [1]. Here we provide data behind the mechanisms involved in Angiotensin II (Ang II) effects on vascular smooth muscle cells (VSMC). Ang II-induced VSMC ROS production is modulated by alpha1beta1 integrin. Ang II also stimulates ROS production in VSMC via p47 (phox) , a NOX2 subunit. Furthermore, Ang II effect on VSMC migration was also inhibited by NOX2 inhibitor. We showed that obtustatin, alpha1beta1 integrin blocker, inhibited Ang II effect on p47 (phox) activation. Ang II effect on ROS production is also PI3K dependent. Finally we showed that NOX1 and Integrin-Linked-Kinase (ILK) are crucial to NOX2 activation. The research provides information about the sequential events of NOX1/alpha1beta1 integrin/ILK/NOX2 in Ang II effects on VSMC. PMID- 26862581 TI - Data in support of NFkappaB and JNK pathways involvement in TLR3-mediated HIV-1 transactivation, expression of IL-6 and transcription factors associated with HIV 1 replication. AB - In the present article, using human monocyte-derived macrophages and cell lines containing integrated copies of the HIV-1 promoter, we show the effects of TLR3 ligands on the pro-inflammatory cytokine IL-6. We further show the effects of TLR3 ligands on HIV-1 transactivation and transcription factors involved in HIV-1 replication. This article complements the data reported by the authors, "Toll Like receptor-3 mediates HIV-1 transactivation via NFkappaB and JNK pathways, and histone acetylation, but prolonged activation suppresses Tat and HIV-1 replication" (Bhargavan et al., 2015) [1], and the interpretation of these data can be found in the research article published by the authors in Cellular Signaling in 2015 (Bhargavan et al., 2015) [1]. PMID- 26862582 TI - Dataset on protein composition of a human plasma sub-proteome able to modulate the Dengue 2 virus infection in Huh 7.5 cells. AB - The four serotypes of dengue virus (DENV1-4) are the causal agents of the emerging disease Dengue Fever and its severe forms. DENV is inoculated into human blood through a mosquito bite. Thus, plasma is an important media for DENV dissemination in infected persons and several important interactions should take place for the virus with human plasma proteins that strongly influence or may determine the course of the infection. This dataset contains 239 proteins identified in the elution fractions of human plasma subjected to DE-52 anion exchange chromatography. Data on DENV2 infection of Huh 7.5 cells in presence of the human plasma fraction is also presented. PMID- 26862583 TI - Comparison of bactericidal and cytotoxic activities of trichogin analogs. AB - Peptaibiotics are a group of membrane active peptides of fungal origin. They typically contain alpha-aminoisobutyric acid (Aib; 1-letter code, U) and other non-coded residues (Toniolo and Bruckner, 2009; Neumann et al., 2015; Benedett et al., 1982) [1], [2], [3] stabilizing their helical structure. Peptaibols are peptaibiotics carrying a 1, 2-aminoalcohol at the C-terminus. When a fatty acid chain (of 8-10 carbon atoms) is present at their N-terminus, they are called lipopeptaibols (Toniolo et al., 2001; Degenkolb et al., 2003) [4], [5]. We found (Tavano et al., 2015) [6] that the lipopeptaibol trichogin displays no antibacterial effects up to 64 uM, against both Gram(-) and Gram(+) bacteria, but kills tumor and healthy human cells via a mechanism requiring both the C-terminal primary alcohol group and the N-terminal n-octanoyl moiety, with EC50s around 4-5 uM. However, the substitution of single Gly residues with Lys strongly improves anti-Gram(+) activity (Tavano et al., 2015; De Zotti, Biondi, Park et al., 2012; De Zotti, Biondi, Peggion et al., 2012) [6], [7], [8]. To further characterize the activity of trichogin analogs as antibiotics and cytotoxic agents, we here manipulated the peptide helix amphipathicity by means of two different substitutions: (i) Aib to Leu (De Zotti et al., 2012) [7] or (ii) multiple Gly to Lys changes (Tavano et al., 2015; De Zotti, Biondi, Park et al., 2012; De Zotti, Biondi, Peggion, Formaggio et al., 2012; De Zotti, Biondi, Peggion, De Poli et al., 2012) [6], [7], [8], [9]. The antibacterial activity against four commensal or opportunistic bacterial species and the cytotoxicity against a panel of 9 healthy and tumor-derived eukaryotic cell types (including erythrocytes) are reported as MIC and EC50 (MTS - [3-(4, 5-dimethylthiazol-2-yl)-5-(3 carboxymethoxyphenyl)-2-(4-sulfophenyl)]-2H-tetrazolium- reduction and LDH - lactate dehydrogenase - release assay). PMID- 26862584 TI - Leaf apoplastic proteome composition in UV-B treated Arabidopsis thaliana mutants impaired in extracellular glutathione degradation. AB - In plants, environmental perturbations often result in oxidative reactions in the apoplastic space, which are counteracted for by enzymatic and non-enzymatic antioxidative systems, including ascorbate and glutathione. However, the occurrence of the latter and its exact role in the extracellular space are not well documented. In Arabidopsis thaliana, the gamma-glutamyl transferase isoform GGT1 bound to the cell wall takes part in the so-called gamma-glutamyl cycle for extracellular glutathione degradation and recovery, and may be implicated in redox sensing and balance. In this work, oxidative conditions were imposed with UV-B radiation and studied in redox altered ggt1 mutants. Elevated UV-B has detrimental effects on plant metabolism, plasma membranes representing a major target for ROS generated by this harmful radiation. The response of ggt1 knockout Arabidopsis leaves to UV-B radiation was assessed by investigating changes in apoplastic protein composition. We then compared the expression changes resulting from the mutation and from the UV-B treatment. Rearrangements occurring in apoplastic protein composition suggest the involvement of hydrogen peroxide, which may ultimately act as a signal. Other important changes related to hormonal effects, cell wall remodeling, and redox activities are also reported. We argue that oxidative stress conditions imposed by UV-B and by disruption of the gamma glutamyl cycle result in similar stress-induced responses, to some degree at least. Data shown here are associated with the article from Trentin et al. (2015) [1]; protein data have been deposited to the PRIDE database (Vizcaino et al., 2014) [2] with identifier PXD001807. PMID- 26862585 TI - Feedback-related potentials in a gambling task with randomised reward. AB - Event-related potentials (ERPs) time-locked to decision outcomes are reported. Participants engaged in a gambling task (see [1] for details) in which they decided between a risky and a safe option (presented as different coloured shapes) on each trial (416 in total). Each decision was associated with (fully randomised) feedback about the reward outcome (Win/Loss) and its magnitude (varying as a function of decision response; 5-9 points for Risky decisions and 1 4 points for Safe decisions). Here, we show data demonstrating: (a) the influence of Win feedback in the preceding outcome (Outcome t-1) on activity related to the current outcome (Outcome t ); (b) difference wave analysis for outcome expectancy separating Expected Outcomes (consecutive Loss trials subtracted from consecutive reward) from Unexpected Outcomes (subtracting Loss t-1Win t trials from Win t-1Loss t trials); (c) difference waves separating Switch and Stay responses for Outcome Expectancy; (d) the effect of magnitude induced by decisions (Risk t vs. Safe t ) on Outcome Expectancy; and finally, (e) expectations reflected by response switch direction (Risk to Safe responses vs. Safe to Risk t ) on the FRN at Outcome t . PMID- 26862586 TI - Quantification of heterotypic granule fusion in human neutrophils by imaging flow cytometry. AB - Human neutrophils are filled with intracellular storage organelles, called granules and secretory vesicles, which differ in their content of soluble matrix proteins and membrane-bound molecules. To date, at least four distinct granule/vesicle subsets have been identified. These organelles may secrete their content extracellularly following mobilization to and fusion with the plasma membrane, but some of them may also fuse with internal membrane-enclosed organelles, typically a plasma membrane-derived phagosome. There are also instances where different granules appear to fuse with one another, a process that would enable mixing of their matrix and membrane components. Such granule fusion enables e.g., myeloperoxidase-processing of intragranular oxygen radicals, a key event in the formation of neutrophil extracellular traps (Bjornsdottir et al., 2015) [1]. Described herein are data that show the quantification of such heterotypic granule-granule fusion by the use of imaging flow cytometry, a technique that combines flow cytometry with microscopy. The analysis described is based on immunofluorescent staining of established granule markers (lactoferrin and/or NGAL for one granule subset; the specific granules, and CD63 for another granule subset, the azurophil granules) and calculation of a colocalization score for resting and PMA-stimulated neutrophils. PMID- 26862587 TI - A complex water network contributes to high-affinity binding in an antibody antigen interface. AB - This data article presents an analysis of structural water molecules in the high affinity interaction between a potent tumor growth inhibiting antibody (fragment), J22.9-xi, and the tumor marker antigen CD269 (B cell maturation antigen, BCMA). The 1.89 A X-ray crystal structure shows exquisite details of the binding interface between the two molecules, which comprises relatively few, mostly hydrophobic, direct contacts but many indirect interactions over solvent waters. These are partly or wholly buried in, and therefore part of, the interface. A partial description of the structure is included in an article on the tumor inhibiting effects of the antibody: "Potent anti-tumor response by targeting B cell maturation antigen (BCMA) in a mouse model of multiple myeloma", Mol. Oncol. 9 (7) (2015) pp. 1348-58. PMID- 26862588 TI - Data describing the effects of dietary bioactive agents on colonic stem cell microRNA and mRNA expression. AB - With the identification of Lgr5 as a definitive marker for intestinal stem cells, we used the highly novel, recently described, Lgr5-EGFP-IRES-cre ER (T2) knock in mouse model. Mice were injected with azoxymethane (AOM, a colon carcinogen) or saline (control) and fed a chemo-protective diet containing n-3 fatty acids and fermentable fiber (n-3 PUFA+pectin) or a control diet (n-6 PUFA + cellulose). Single cells were isolated from colonic mucosa crypts and three discrete populations of cells were collected via fluorescence activated cell sorting (FACS): Lgr5(high) (stem cells), Lgr5(low) (daughter cells) and Lgr5(negative) (differentiated cells). microRNA profiling and RNA sequencing were performed from the same sample and analyzed. These data refer to 'Comparative effects of diet and carcinogen on microRNA expression in the stem cell niche of the mouse colonic crypt' (Shah et al., 2016) [5]. PMID- 26862589 TI - Data regarding M1 muscarinic receptor-mediated modulation of hepatic catalase activity in response to oxidative stress. AB - We recently demonstrated the role of M1 muscarinic receptors (M1R) in modulating oxidative stress in liver and hepatocytes (Urrunaga et al., 2015) [1]. Here we provide data regarding the effect of a novel M1R agonist, VU0357017 (Lebois et al., 2010) [2], on H2O2-mediated hepatocyte injury, the effect of an M1R antagonist VU0255035 (Sheffler et al., 2009) [3] on catalase and super oxide dismutase (SOD) activities in H2O2-treated hepatocytes in vitro, and finally, the effect of M1R ablation on hepatic catalase activity in acetaminophen (APAP) treated mice. PMID- 26862590 TI - Growth and Survival of the American Oyster Crassostrea virginica in Jamaica Bay, New York. AB - Jamaica Bay is a major inlet opening to the Atlantic Ocean. It was abundant with oysters until early 1900's. Over-harvesting, pressure from predators, parasitic invasion and declining water quality often are cited as causes. Despite actions to arrest and reverse the pollution, oysters are not reestablished. We are studying factors relating to the rehabitation of Crassostrea virginica in Jamaica Bay to determine if the water quality and environmental conditions are suitable for their survival. Oysters placed in Jamaica Bay grew well when housed in protective containers and growth was influenced by placement near the sediment as compared to the surface. Oysters placed 1 foot above the sediment grew larger that those suspended 1 foot below the surface. Water temperature, pH, turbidity, salinity, conductivity, chlorophyll-a and dissolved O2 were taken to compare water quality at each site. To study growth and survival in a more natural condition, oyster seed and adults were placed just off the bottom in unprotected containers and photographed. After 1 year they are growing and surviving well and there has been evidence of reproduction. Thus far there are no serious signs of predation by crabs or starfish. The study shows that Jamaica Bay water quality is suitable for oyster growth under the various conditions of our experiments. PMID- 26862591 TI - Determining the structural stability of UiO-67 with respect to time: a solid state NMR investigation. AB - The stability of UiO-67 has been questioned for some time. We have used solid state NMR to investigate the temporal stability of this MOF. Proper activation is necessary to achieve optimal surface area. However, even with proper activation, the long-term (30+ days) fate of UiO-67 is hydrolysis of the linker-metal bonds and, ultimately, pore collapse. PMID- 26862592 TI - Low loadings of platinum on transition metal carbides for hydrogen oxidation and evolution reactions in alkaline electrolytes. AB - Low-loadings of Pt supported over six transition metal carbide (Pt/TMC) powder catalysts were synthesized and evaluated for hydrogen oxidation and evolution reactions in an alkaline electrolyte. The roughness factor of each Pt/TMC catalyst was different, indicating that the carbide supports affect the dispersion of Pt. Furthermore, when normalized by the corresponding roughness factors, all Pt/TMC catalysts were found to have similar intrinsic activities that were comparable to the state-of-the-art commercial Pt/C electrocatalysts. PMID- 26862593 TI - Nanoparticle-enhanced fluorescence emission for non-separation assays of carbohydrates using a boronic acid-alizarin complex. AB - Addition of crosslinked polymer nanoparticles into a solution of a 3 nitrophenylboronic acid-alizarin complex leads to significant enhancement of fluorescence emission. Using the nanoparticle-enhanced boronic acid-alizarin system has improved greatly the sensitivity and extended the dynamic range of separation-free fluorescence assays for carbohydrates. PMID- 26862594 TI - New insights into the mechanism of interaction between CO2 and polymers from thermodynamic parameters obtained by in situ ATR-FTIR spectroscopy. AB - This work reports new physical insights of the thermodynamic parameters and mechanisms of possible interactions occurring in polymers subjected to high pressure CO2. ATR-FTIR spectroscopy has been used in situ to determine the thermodynamic parameters of the intermolecular interactions between CO2 and different functional groups of the polymers capable of specific interactions with sorbed CO2 molecules. Based on the measured ATR-FTIR spectra of the polymer samples subjected to high-pressure CO2 (30 bar) at different temperatures (300 340 K), it was possible to characterize polymer-polymer and CO2-polymer interactions. Particularly, the enthalpy and entropy of the formation of the specific non-covalent complexes between CO2 and the hydroxy (-OH), carbonyl (C[double bond, length as m-dash]O) and hydroxyimino ([double bond, length as m dash]N-OH) functional groups of the polymer samples have been measured. Furthermore, the obtained spectroscopic results have provided an opportunity for the structure of these complexes to be proposed. An interesting phenomenon regarding the behavior of CO2/polymer systems has also been observed. It has been found that only for the polyketone, the value of enthalpy was negative indicating an exothermic process during the formation of the CO2-polymer non-covalent complexes. Conversely, for the polyoxime and polyalcohol samples there is a positive enthalpy determined. This is a result of the initial polymer-polymer interactions requiring more energy to break than is released during the formation of the CO2-polymer complex. The effect of increasing temperature to facilitate the breaking of the polymer-polymer interactions has also been observed. Hence, a mechanism for the formation of CO2-polymer complexes was suggested based on these results, which occurs via a two-step process: (1) the breaking of the existing polymer-polymer interactions followed by (2) the formation of new CO2-polymer non covalent interactions. PMID- 26862595 TI - Theory and simulation of DNA-coated colloids: a guide for rational design. AB - By exploiting the exquisite selectivity of DNA hybridization, DNA-coated colloids (DNACCs) can be made to self-assemble in a wide variety of structures. The beauty of this system stems largely from its exceptional versatility and from the fact that a proper choice of the grafted DNA sequences yields fine control over the colloidal interactions. Theory and simulations have an important role to play in the optimal design of self assembling DNACCs. At present, the powerful model based design tools are not widely used, because the theoretical literature is fragmented and the connection between different theories is often not evident. In this Perspective, we aim to discuss the similarities and differences between the different models that have been described in the literature, their underlying assumptions, their strengths and their weaknesses. Using the tools described in the present Review, it should be possible to move towards a more rational design of novel self-assembling structures of DNACCs and, more generally, of systems where ligand-receptor are used to control interactions. PMID- 26862596 TI - Water ingress into a casein film quantified using time-resolved neutron imaging. AB - The migration of water into a casein film was probed with neutron radiography. From the neutron transmission images, the evolution of the water saturation profiles was extracted. The results indicate that the water influx is dominated by imbibition but also contains a diffusional component. The time dependence of the water ingress was quantified using a diffusion-like equation previously also applied to imbibition. A water transport coefficient D = 0.9 * 10(-9) m(2) s(-1) was found. This value and direct observation of the images indicate that the time taken for a typical adhesive casein-based layer to become saturated with water is of the order of hours. PMID- 26862597 TI - Enhanced sampling simulation analysis of the structure of lignin in the THF-water miscibility gap. AB - Using temperature replica-exchange molecular dynamics, we characterize a globule to-coil transition for a softwood-like lignin biopolymer in a tetrahydrofuran (THF)-water cosolvent system at temperatures at which the cosolvent undergoes a de-mixing transition. The lignin is found to be in a coil state, similar to that in the high-temperature miscible region. Analysis of the transition kinetics indicates that THF acts in a surfactant-like fashion. The present study thus suggests that THF-water based pretreatments may efficiently remove lignin from biomass even at relatively low (non-water boiling) temperatures. PMID- 26862598 TI - Morphology-enhanced conductivity in dry ionic liquids. AB - Ionic liquids exhibit fascinating nanoscale morphological phases and are promising materials for energy storage applications. Liquid crystalline order emerges in ionic liquids with specific chemical structures. Here, we investigate the phase behaviour and related ionic conductivities of dry ionic liquids, using extensive molecular dynamics simulations. Temperature dependence, properties of polymeric tail and excluded volume symmetry of the amphiphilic ionic liquid molecules are investigated in large scale systems with both short and long-range Coulomb interactions. Our results suggest that by adjusting stiffness and steric interactions of the amphiphilic molecules, lamellar or 3D continuous phases result in these molecular salts. The resulting phases are composed of ion rich and ion pure domains. In 3D phases, ion rich clusters form ionic channels and have significant effects on the conductive properties of the observed nano phases. If there is no excluded-volume asymmetry along the molecules, mostly lamellar phases with anisotropic conductivities emerge. If the steric interactions become asymmetric, lamellar phases are replaced by complex 3D continuous phases. Within the temperature ranges for which morphological phases are observed, conductivities exhibit low-temperature maxima in accord with experiments on ionic liquid crystals. Stiffer molecules increase the high conductivity interval and strengthen temperature-resistance of morphological phases. Increasing the steric interactions of cation leads to higher conductivities. Moreover, at low monomeric volume fractions and at low temperatures, cavities are observed in the nano-phases of flexible ionic liquids. We also demonstrate that, in the absence of electrostatic interactions, the morphology is distorted. Our findings inspire new design principles for room temperature ionic liquids and help explain previously-reported experimental data. PMID- 26862599 TI - Simultaneous enhancement of magnetic and ferroelectric properties in Dy and Cr co doped BiFeO3 nanoparticles. AB - Multiferroic BiFeO3 (BFO), Bi0.95Dy0.05FeO3 and Bi0.95Dy0.05Fe0.95Cr0.05O3 samples were successfully synthesized by a carbon microsphere-assisted sol-gel (CSG) method. X-ray diffraction analysis confirmed a lattice distortion from a rhombohedral structure to a tetragonal structure upon doping Dy and Cr in BFO. The morphology of BFO and doped BFO could be effectively controlled to form nanoparticles, due to the nucleation sites of the carbon microspheres. The co doping of Dy and Cr in BFO had a significant improvement effect on the magnetic properties, with the remnant magnetization being 0.557 emu g(-1), due to the structural phase transition, size effects and the strong ferromagnetic interaction between Fe(3+)-O-Cr(3+) ions arising from Cr substitution. Meanwhile, the doping of Dy into BFO effectively reduced the leakage current and enhanced the ferroelectric properties. The simultaneous enhancement of magnetic and ferroelectric properties shows the great potential application of Dy- and Cr-co doped BFO in future multifunctional devices. PMID- 26862600 TI - Binding properties of pendimethalin herbicide to DNA: multispectroscopic and molecular docking approaches. AB - Pendimethalin (PND) is a systemic herbicide widely used on rice, cotton, peas, wheat, potatoes, fruits, nuts and other residential and non-residential crops; however, it concurrently exerts toxic effects on beneficial organisms like earthworms, aquatic invertebrates and other non-targeted animals including humans. Most likely, the genotoxicity of agrochemicals/drugs is modulated through cellular distribution of bound DNA. Therefore, the in vitro interaction of PND with calf thymus DNA (ctDNA) has been investigated using various sensitive biophysical techniques to ascertain its binding mechanism. UV-visible absorption and fluorescence spectra suggested the formation of a complex between PND and ctDNA. The binding constant of the PND-ctDNA complex was found to be around 10(4) M(-1) using steady state fluorescence titration. The calculated positive values of enthalpy and entropy changes suggested that the binding reaction was predominantly driven by hydrophobic interactions. Competitive displacement studies using acridine orange (AO), ethidium bromide (EB) and Hoechst dye suggested intercalation of PND molecules into the double helix of ctDNA by replacing the bound AO and EB probes. An increase in the viscosity and melting temperature of ctDNA and a decrease in iodine-quenching also support the intercalative binding of PND with ctDNA. Molecular docking analysis further confirmed the specific binding mode of PND between adjacent 'G-C' base pairs of ctDNA. PMID- 26862601 TI - Heterogeneous dynamics and its length scale in simple ionic liquid models: a computational study. AB - We numerically investigate the dynamic heterogeneity and its length scale found in coarse-grained ionic liquid model systems. In our ionic liquid model systems, cations are modeled as dimers with a positive charge, while anions are modeled as monomers with a negative charge, respectively. To study the effect of the charge distributions on the cations, two ionic liquid models with different charge distributions are used and the model with a neutral charge is also considered as a counterpart. To reveal the heterogeneous dynamics in the model systems, we examine spatial distributions of displacement and time distributions of exchange and persistence times. All the models show a significant increase of the dynamic heterogeneity as the temperature is lowered. The dynamic heterogeneity is quantified via the well-known four-point susceptibility, chi4(t), which measures the fluctuations of a time correlation function. The dynamic correlation length is calculated by fitting the dynamic structure factor, S4(k,t), with the Ornstein Zernike form at the time scale at which the dynamic heterogeneity reaches the maximum value. The obtained time and length scales exhibit a power law relation at the low temperatures, similar to various supercooled liquid models. In particular, the charged model systems show unusual crossover behaviors which are not observed in the uncharged model system. We ascribe the crossover behavior to the enhanced cage effect caused by charges on the particles. PMID- 26862602 TI - In vivo degeneration and the fate of inorganic nanoparticles. AB - What happens to inorganic nanoparticles (NPs), such as plasmonic gold or silver, superparamagnetic iron oxide, or fluorescent quantum dot NPs after they have been administrated to a living being? This review discusses the integrity, biodistribution, and fate of NPs after in vivo administration. The hybrid nature of the NPs is described, conceptually divided into the inorganic core, the engineered surface coating comprising of the ligand shell and optionally also bio conjugates, and the corona of adsorbed biological molecules. Empirical evidence shows that all of these three compounds may degrade individually in vivo and can drastically modify the life cycle and biodistribution of the whole heterostructure. Thus, the NPs may be decomposed into different parts, whose biodistribution and fate would need to be analyzed individually. Multiple labeling and quantification strategies for such a purpose will be discussed. All reviewed data indicate that NPs in vivo should no longer be considered as homogeneous entities, but should be seen as inorganic/organic/biological nano hybrids with complex and intricately linked distribution and degradation pathways. PMID- 26862603 TI - A microfluidic opto-caloric switch for sorting of particles by using 3D hydrodynamic focusing based on SLE fabrication capabilities. AB - In a miniaturised flow switch fluid flows are controlled by reducing the local viscosity via absorption of laser radiation. Through this, the local flow rates are increased to switch the outlet port of a fluid flow carrying the analyte. The microfluidic chip is fabricated using Selective Laser-Induced Etching (SLE). SLE allows novel 3D-hydrodynamic focusing, realising circular shaped channel cross sections and adapting interaction volume geometries to the profile of the laser radiation for optimised absorption. The performance of the switch is validated experimentally with a dyed analyte and video image processing. The ability to sort particles like cells is demonstrated at 8 Hz using polystyrene beads having a diameter of 8 MUm. PMID- 26862604 TI - Examine the patient, not just the evidence. Author's response. PMID- 26862605 TI - Growth Potential of Listeria Monocytogenes and Staphylococcus Aureus on Fresh Cut Tropical Fruits. AB - The objective of this study was to evaluate the fate of Staphylococcus aureus, Listeria monocytogenes, and natural microbiota on fresh-cut tropical fruits (pitaya, mango, papaya and pineapple) with commercial PVC film at different storage temperature (5, 13, and 25 degrees C). The results showed that S. aureus, L. monocytogenes, and natural microbiota increased significantly on fresh cut tropical fruits at 25 degrees C. Both pathogen and natural microbiota were able to grow on fresh-cut tropical fruits at 13 degrees C. The maximum population of L. monocytogenes was higher than that of S. aureus on fresh-cut tropical fruits. L. monocytogenes and S. aureus could survive without growth on fresh-cut pitaya, mango, and papaya at 5 degrees C. The population of L. monocytogenes declined significantly on fresh-cut pineapple at all temperature, indicating composition of fresh-cut pineapple could inhibit growth of L. monocytogenes. However, S. aureus was still able to grow on fresh-cut pineapple at storage temperature. Thus, this study suggests that 4 kinds of fresh-cut tropical fruits (pitaya, mango, papaya, and pineapple) should be stored at low temperature to extend shelf life as well as to ensure the safety of fresh-cut fruits. PRACTICAL APPLICATION: The data collected in this study demonstrated that L. monocytogenes and S. aureus were able to grow on fresh-cut tropical fruits at different temperatures. These results could be of interest in knowing the capacity of tropical fruits to support the growth of L. monocytogenes and S. aureus. This information may also be useful to local and state regulatory officials responsible for food safety. PMID- 26862606 TI - [IS IT USEFUL TO USE THE BODY MASS INDEX TO ASSESS OBESITY IN MUSCULAR PEOPLE?]. PMID- 26862607 TI - [PERFORMANCE OF ENTERO-INSULAR AXIS IN AN ATHLETIC POPULATION: DIET AND EXERCISE INFLUENCE]. PMID- 26862608 TI - Response. PMID- 26862609 TI - Eric H. Davidson (1937-2015). PMID- 26862610 TI - RELIABILITY AND VALIDITY OF SUBJECTIVE ASSESSMENT OF LUMBAR LORDOSIS IN CONVENTIONAL RADIOGRAPHY. AB - BACKGROUND: Reliability and validity studies of different lumbar curvature analysis and measurement techniques have been documented however there is limited literature on the reliability and validity of subjective visual analysis. Radiological assessment of lumbar lordotic curve aids in early diagnosis of conditions even before neurologic changes set in. OBJECTIVE: To ascertain the level of reliability and validity of subjective assessment of lumbar lordosis in conventional radiography. DESIGN: A blinded, repeated-measures diagnostic test was carried out on lumbar spine x-ray radiographs. SETTING: Radiology Department at Joint Clinical Research Centre (JCRC), Mengo-Kampala-Uganda. SUBJECTS: Seventy (70) lateral lumbar x-ray films were used for this study and were obtained from the archive of JCRC radiology department at Butikiro house, Mengo-Kampala. RESULTS: Poor observer agreement, both inter- and intra-observer, with kappa values of 0.16 was found. Inter-observer agreement was poorer than intra-observer agreement. Kappa values significantly rose when the lumbar lordosis was clustered into four categories without grading each abnormality. CONCLUSION: The results confirm that subjective assessment of lumbar lordosis has low reliability and validity. Film quality has limited influence on the observer reliability. This study further shows that fewer scale categories of lordosis abnormalities produce better observer reliability. PMID- 26862611 TI - PREVALENCE OF CERVICAL CYTOLOGY ABNORMALITIES AMONG HIV INFECTED WOMEN AT RWANDA MILITARY HOSPITAL. AB - OBJECTIVES: To establish the prevalence of cervical cytology abnormalities, determine the correlation between CD4+ cell count and abnormal Pap smear, determine the correlation between WHO-HIV staging and abnormal pap smear among HIV infected women attending HIV clinic at Rwanda Military Hospital. DESIGN: Cross-sectional descriptive study. SETTING: Rwanda Military Hospital Kigali, Rwanda. SUBJECTS: All HIV-positive women, 18-69 years who had been or were sexually active and were attending the HIV-clinic and consented to participate in the study. RESULTS: Two hundred and ninety three women infected with HIV had cervical smear taken for cytology. Of the 293 women who were recruited for the study, cervical Squamous Intra epithelial Lesion (SIL) were present in 58 (20%). Of those with cervical SIL, 33 (56.89%) women had low-grade SIL, 15 (25.86%) had Atypical Squamous Cells of Undetermined Significance (ASCUS), six (10.34%) had high-grade SIL, three (5.17%) had Squamous cell carcinoma (SCC) and one (1.72%) had Atypical Glandular Cells of Undetermined Significance (AGUS). In the current study, use of ARV drugs was not associated with a reduction in the risk of cervical SIL. CONCLUSION: A high prevalence of cervical SIL was found among HIV infected women at Rwanda Military Hospital. Increased immune suppression was significantly associated with cervical SIL. PMID- 26862612 TI - CONTROVERSY ABOUT EMBRYOGENESIS AND ORGANISATION OF HUMAN FEMALE URETHRA: A REVIEW. AB - OBJECTIVE: To assess current knowledge on development and associated structures. DATA SOURCES: Current scientific publications in the pubmed data base on the development of human female urethra were reviewed. The embryology of human female urethra and its associated structures is presented. STUDY SELECTION: The following search words: urethra development, female urethra development, and male urethra development were used. DATA EXTRACTION: The first 100 publications from urethra development search and thereafter 100 publications excluding those in the first search were reviewed to determine whether they described development of female urethra. DATA SYNTHESIS: There are limited studies describing the formation of female urethra. Unlike male urethra, female urethra does not undergo masculinisation meaning there is no formation of clitoral urethra. Like the male urethra, there are female urethra associated glands whose presence and functions remain speculative. Female urethra associated structures including Skene's glands also referred to as female prostate, corpus spongiosum of female urethra and what has been described as the G-Spot may all be congenital malformations considering that they are not uniformly present. CONCLUSIONS: Female urethra development differs from that of males though there are some similarities. Studies to elucidate the development of female urethra are needed to clarify some of the misconceptions and to provide embryological explanation of gross and histological features of female urethra. PMID- 26862613 TI - ASSESSMENT OF THE LIVING CONDITIONS OF RURAL BASED PEOPLE LIVING WITH HIV/AIDS WITH CLINICAL PRESENTATIONS IN NIGERIA. AB - OBJECTIVE: To describe the living conditions of rural based people living with HIV/AIDS (PLWHA) and their clinical presentations DESIGN: descriptive cross sectional study, SETTING: University College Hospital, Ibadan. SUBJECTS: PLWHA on anti-retroviral therapy. RESULTS: One hundred and fifty PLWHA participated. The mean age of the respondents was 28.7 +/- 8.9 years. Majority of the respondents visited had advanced disease (97%), were poor (75%) and presented with opportunistic infections such as oral candidiasis (92%), chronic diarrhoea (70%) and pulmonary tuberculosis (46%). Majority were treated for malaria (72%) and anaemia (61%). All respondents lived in homes predisposed to these opportunistic infections. They drink unsafe water and had poor disposal of their domestic wastes. CONCLUSION: PLWHA visited lived in homes that predispose them to various opportunistic infections. Improved living conditions and economic empowerment will improve the health conditions of PLWHA. PMID- 26862614 TI - IMPLEMENTING TOOLS TO PROMOTE ADHERENCE TO ANTIRETROVIRAL THERAPY AT FACILITIES IN KENYA. AB - BACKGROUND: Lack of effective systems and tools to identify and track defaulters are some of the factors that pose challenges in adherence monitoring for patients on anti-retroviral treatment (ART). An intervention was performed to introduce a facility-based appointment keeping system, and a revised clinic form to monitor patients' adherence to ART. OBJECTIVE: To assess facility staff perceptions of, motivation for and self-reported practice in the implementation, and on the use of adherence-based indicators to inform decisions for performance improvement. DESIGN: Qualitative explorative study aiming to evaluate a quasi-experimental intervention. SETTINGS: Six conveniently sampled health facilities in Kenya located in Central, Eastern and Rift Valley provinces. SUBJECTS: Thirty-six clinic staff members were interviewed, six at each facility, including facility managers, clinicians, nursing and pharmacy staff, counsellors, health records information officers and social workers. Analysis was performed in line with the Pettigrew and Whipp framework. RESULTS: Providers perceived that the intervention had empowered them to assess their clinic's daily workload and to identify those patients who missed their appointments. Factors enhancing the positive uptake of the intervention included the availability of tools to monitor appointment keeping, training on adherence principles and supervisory support. Early detection of treatment defaulters helped the providers design targeted patient support to enhance appointment keeping. CONCLUSION: The effect of the intervention led to implementation of changes within the clinic to enhance patients' appointment keeping and improve adherence to treatment. We expect the reported and observed changes to be sustainable as data generation and calculation of indicators to inform decision-making were performed by the providers themselves. PMID- 26862615 TI - NURSES INFECTION PREVENTION PRACTICES IN HANDLING INJECTIONS: A CASE OF RIFT VALLEY PROVINCIAL HOSPITAL IN KENYA. AB - OBJECTIVE: To analyse the infection prevention practices in handling of injections by nurses in Rift Valley Provincial Hospital in Kenya. DESIGN: A cross sectional observational study. SETTING: Rift Valley Provincial hospital which is a level five health facility situated in Nakuru County, Kenya. SUBJECTS: A sample of 386 injection procedures attributed to the nurses in Rift Valley Provincial Hospital was considered for this study. RESULTS: The study established that among all the injections administered in this study, 43.7% (386) adhered to aseptic techniques. Over seventy five percent (76.9%, n = 386) of the observed injections procedures did not involve the hand-washing, 53.4% (n = 206) did not involve swabbing of a vial rubber cap with alcohol swabs and 95.1%(n = 263) involved using of multidose drug in more than one designated patient. Over ninety five percent (95.6%, n = 364) of the observed procedures involved use of sterile the syringe bit of the devices only while the rest used either clean or contaminated syringes. Around forty percent (42.2%, n = 316) of the injections preparation was done elsewhere (not at the patient bedside) before administration. Slightly over thirty five percent (36.6%, n = 386) of the injections were administered immediately upon reconstitution(at the right time). The study also established the use of aseptic techniques to reconstitute and administer was significantly related to the number of nurses to patients ratio per shift (X2(1) = 3.5: p = 0.04). CONCLUSION: The findings of this study indicate that patient safety in public hospital is still relatively low. The adherence to basic infection prevention procedures/aseptic techniques in handling of injections by health workers is still a concern. The adherence to aseptic techniques in handling injections is significantly associated with the nurses to patients ratios. Therefore, it is imperative to improve nurse to patient ratio in public health facilities in Kenya. PMID- 26862616 TI - THE DETERMINANTS OF HEALTH RELATED QUALITY OF LIFE OF PATIENTS ON MAINTENANCE HAEMODIALYSIS AT KENYATTA NATIONAL HOSPITAL, KENYA. AB - BACKGROUND: Health related quality of life (HRQOL) is increasingly being recognised as a primary outcome measure in the treatment of end stage renal disease. In addition to being an important surrogate marker of quality of care in patients on maintenance haemodialysis, HRQOL measures have being shown to be robust predictors of mortality and morbidity. OBJECTIVE: To determine the health related quality of life and its determinants in patients on maintenance haemodialysis at the Kenyatta National Hospital. DESIGN: A cross-sectional descriptive study. SETTING: Renal unit, Kenyatta National Hospital. SUBJECTS: Adult patients with end stage renal disease on maintenance haemodialysis. RESULTS: The mean physical composite summary and mental composite summary scores were 39.09 +/- 9.49 and 41.87 +/- 10.56 respectively. The burden of kidney disease sub-scale, symptom and problems sub-scale and effect of kidney disease on daily life sub-scale scores were 16.15 +/- 21.83, 73.46 +/- 18.06 and 67.63 +/- 23.45 respectively. No significant correlations were found between the health related quality of life scores, socio-demographic and clinical factors assessed. CONCLUSION: The health-related quality of life of patients on maintenance haemodialysis is reduced. The physical quality of life is more affected than the mental quality of life. No independent determinants of health-related quality of life were identified. PMID- 26862617 TI - ANTHROPOMETRIC STUDY OF ISCHIOPUBIC INDEX OF THE ISOKO AND BENIN IN NIGERIA. AB - BACKGROUND: The ischiopubic index is calculated by dividing the pubic length by the ischial length and multiplying by 100. It has been said to be one of the parameters affecting the pelvic inlet and this is of interest to obstetricians and anatomic anthropologists. OBJECTIVES: To determine and compare the pubic length, ischial length andischiopubic index among the males and females of Isoko and Bini ethnic groups of Nigeria. DESIGN: A retrospective cross sectional study. SETTING: University of Benin teaching hospital (UBTH), Irrua Specialist teaching hospital (ISTH) and Eku Baptist Hospital. SUBJECTS: Four hundred antero-posterior radiographs; two hundred for the Isoko (males 105 and females 95) and two hundred also for the Bini (males 110 and females 90) adult pelvis in the age range of 18 65 years were evaluated. RESULTS: Pubic length, ischial length, and ischiopubic index were measured. The mean pubic length, mean ischial length and mean ischiopubic index of Isoko males are respectively (mm) 78.42 +/- 3.40, 69.41 +/- 5.10, 75.2-97.5, 87.52 +/- 1.30. The range and point of demarcation are (mm): 75.2-97.5, < 86.22. For Isoko females, the mean pubic length, mean ischial length and mean ischiopubic index are (mm): 81.20 +/- 5.0, 74.30 +/- 6.10, 106.21 +/- 9.10. The range and demarcation point are (mm): 87-125.10, < 97.11. The mean pubic length, mean ischial length and mean ischiopubic index of Bini males are respectively (mm): 74.32 +/- 5.40, 82.71 +/- 7.20, 88.72 +/- 2.40. The range and point of demarcation are (mm) 70-98,< 86.32. For Bini females they are (mm); 86.48 +/- 4.20, 78.61+/- 7.41, 112.21 +/- 7.71. The range and point of demarcation are (mm): 84.1-132.50, < 104.50 respectively. CONCLUSION: The study showed sexual dimorphism in the ischipubic index of the study population and a significant difference in actual mean values and demarking points between the two population groups studied. This contributes growing database of anthropologically and obstetrically significant data for ethnic groups in Nigeria and could help in identification of skeletal remains in the hitherto restive Nigerian Niger-Delta region. PMID- 26862618 TI - CHALLENGES IN MANAGEMENT OF WARFARIN ANTI-COAGULATION IN ADVANCED HIV/AIDS PATIENTS WITH VENOUS THROMBOTIC EVENTS--A CASE SERIES FROM A RESEARCH CLINIC IN RURAL KERICHO, KENYA. AB - BACKGROUND: Venous thrombotic events (VTE) occur at high ratesin HIV/AIDS patients and are likely under-diagnosed in rural sub-Saharan Africa. OBJECTIVE: To describe clinical presentations and challenges in the management of VTE in patients with advanced HIV/AIDS. DESIGN: Case series from patients enrolled in a prospective observational cohort study. SETTINGS: A clinical research centre in rural Kericho, Kenya. SUBJECTS: Two hundred patients with median age 38 (30-47) years, BMI 16.9 (12.4-20.3) kg/m2, haemoglobin 9.3 (6.8-13.4) g/dL, CD4+ T-cell count 27 (4-77) cells/mm and plasma HIV RNA 5.23 (3.70-5.88) log10 copies/mL. INTERVENTIONS: VTE cases were diagnosed by clinical presentation and Doppler/ radiographic confirmation. Anti-coagulation therapy was managed by a multidisciplinary team; patients were initiated on enoxaparin or heparin followed by warfarin. RESULTS: Over two years,11patients (5.5%) experienced VTE. All but one (10/11,90.9%) case occurred within six months of starting ART. Nine patients had peripheral VTE (five popliteal, four femoral) and two had cerebral sinus thromboses. VTE was diagnosed 52 (1-469) days after ART initiation, and 81.8% of cases were outpatients at presentation. All patients received at least one concomitant medication that could significantly interact with warfarin (efavirenz, nevirapine, lopinavir/ritonavir, rifampicin, trimethoprim sulfamethoxazole, and fluconazole). A median of 39 (10-180) days and eight (4-22) additional clinic visits were required to achieve/maintain a therapeutic INR of 2 3. Two minor bleeding complications occurred. No recurrent VTE cases were observed. CONCLUSION: Consideration of VTE and preparedness for management in patients with advanced HIV/AIDS starting ART is critical in sub-Saharan Africa. Overcoming challenges in anti-coagulation is possible in rural settings using a multidisciplinary team approach. PMID- 26862619 TI - COMPLEMENTARY TECHNIQUES OF PERCUTANEOUS CLOSURE OF DUCTUS ARTERIOSUS USING DETACHABLE COOK COILS AND AMPLATZER DEVICES. AB - BACKGROUND: Patent Ductus Arteriosus (PDA) is a commoncardiac malformation whose treatment locally has been surgical ligation via a lateral thoracotomy. Device closure of the ductus was first performed at the Mater hospital in 1999 in a ten year old male using a five millilitre detachable cook coil. In 2000 the Amplatzer device was introduced to close larger ducts. Subsequently these devices have been used interchangeably to close both small and large ducts. We report this single centre experience of percutaneous PDA closure in a resource-limited setting; utilising the two techniques. OBJECTIVE: To describe our experience of trans catheter closure of small and large ducts using either the detachable Cook coils or the Amplatzer occluders at the Mater Hospital Nairobi. DESIGN: A descriptive retrospective cohort study. Setting: The Mater Hospital, Nairobi, Kenya. SUBJECTS: Patients with clinical and echo-cardiographic features of patent ductus arteriosus who underwent cardiac catheterisation and angiography followed by device embolisation of the ductus. RESULTS: From April 1999 to October 2009 a total of ninety eight subjects were recruited. into the study. Sixty nine (70%) of these subjects had the ducts closed using the Amplatzer devices, while twenty nine (30%) were embolised using the cook detachable coils. Three of the subjects in the coil group had the ducts embolised using the double technique while the rest were embolised using single coils. Various coil sizes four to eight millimetres were used in patients with small to medium ducts (two to seven millimetres) whereas the Amplatzer duct occluder was successfully used in all the duct sizes. The Amplatzer atrial septal occluder device was used to close very large ducts in two of the patients. The overall success rate was 93.1%, but the coil group had higher failure rate of 6.9% compared to the Amplatzer group of 3%. One patient in the Amplatzer group had a late embolisation requiring surgical retrieval at one month post occlusion. There were no mortalities. CONCLUSION: Transcatheter device occlusion of PDA is a safe and alternative to PMID- 26862620 TI - NUTRITIONAL STATUS OF CHILDREN ADMITTED FOR DIARRHOEAL DISEASES IN A REFERRAL HOSPITAL IN WESTERN KENYA. AB - OBJECTIVES: To determine the prevalence of malnutrition among children admitted with acute diarrhoea disease at Moi Teaching and Referral Hospital and to establish the effect of malnutrition on duration of hospital stay. DESIGN: Prospective observational study. SETTING: Paediatric wards of Moi Teaching and Referral Hospital, Eldoret, Kenya. SUBJECTS: A total of 191 children aged 6 and 59 months admitted with acute diarrhoea disease, without chronic co-morbidities or visible severe malnutrition, were systematically enrolled into the study between November 2011 and March 2012. OUTCOME MEASURES: Nutritional status based on WHO WHZ scores taken at admission and duration of hospital stay. RESULTS: The mean age was 13.2 months with a male to female sex ratio of 1.16:1. Of all the children seen with acute diarrhoeal diseases, 43.9% had acute malnutrition (<-2 WHZ score), with 12% being severely malnourished (<-3 Z score). Average duration of hospital stay was 3.36 (SD=1.54) days. Among those with malnutrition the average duration of stay was 3.39 (SD=1.48) days while for those without malnutrition it was 3.21(SD=1.20) days, which was not statistically different. No death was reported. WHO weight for Height Z scores picked 12% of severe form of malnutrition missed out by Welcome Trust classification (weight for age). CONCLUSION: Routine anthrometry including weight for height identifies more children with malnutrition in acute diarrhoeal diseases. Presence of malnutrition did not affect duration of hospital stay. PMID- 26862621 TI - IMPACT OF CLINICAL OFFICER ANAESTHETIST TRAINING PROGRAMME AT THE KENYA MEDICAL TRAINING COLLEGE, NAKURU, ON TRAINEE SATISFACTION, QUALITY OF PRACTICE, AND CADRE SHORTFALL ALLEVIATION. AB - OBJECTIVE: To determine the impact of Clinical Officer (C.O) Anaesthetist Training programme at Kenya Medical Training College (KMTC) Nakuru, on Trainee satisfaction, quality of practice and cadre shortfall alleviation. DESIGN: Cross sectional descriptive study. SETTING: Kenya Medical Training College, Nakuru. SUBJECTS: All thirty one Clinical Officer Anaesthetist graduates from KMTC Nakuru, since the training programme started 8 years ago. RESULTS: Twenty nine of the 31 C.O Anaesthetist graduates responded. Twenty six of the 29 respondents (89.7%) passed in the final qualifying examination in the first sitting. Twenty one (72.4%) are working in Public health facilities. All graduates are distributed in 16 out of the 47 counties in Kenya. Twenty six (89.7%) are satisfied with the training. Their average working week is 54 hours, with a median of 45 working hours a week. They recommend an improvement in peripheral nerve blocks and epidural training in the 2005 curriculum. CONCLUSION: C.O Anaesthetist training in KMTC Nakuru over the last eight years has produced self reported satisfied, adequately trained graduates and has had an impact in alleviating shortage of this cadre in Kenya. Improvement in peripheral nerve blocks and epidural training is needed. PMID- 26862622 TI - MOLECULAR CHARACTERISATION OF ECHINOCOCCUS GRANULOSUS SPECIES/STRAINS IN HUMAN INFECTIONS FROM TURKANA, KENYA. AB - BACKGROUND: Cystic echinococcosis (CE) or hydatid disease is a neglected, economically important zoonotic disease endemic in pastoralist communities, in particular the Turkana community of Kenya. It is caused by the larval stage of the highly diverse species complex of Echinococcusgranulosus sensu lato (s.l). The situation on the genetic diversity in humans in Kenya is not well established. OBJECTIVE: To characterise Echinococcus granulosus (s.1) species/strains isolated from humans undergoing surgery in Turkana, Kenya. DESIGN: A Cross sectional study. SETTING: The Kakuma Mission Hospital and Centre for Microbiology Research, Kenya Medical Research Institute. SUBJECTS: Eighty (80) parasite samples from 26 subjects were analysed by Polymerase chain reaction -Restriction fragment length polymorphism (PCR-RFLP) targeting the nad 1 gene for molecular characterization. RESULTS: Two different genotypes of E. granulosus were identified from the samples analysed: E. granulosus sensu stricto (G1-G3) 85% of the samples analysed and E. canadensis G6/7 (15%). Most of the hydatid cysts (35%) were isolated from the liver. Other sites where cysts were isolated from include: kidney, abdomen, omentum, retroperitonium and the submandibular. Majority of cysts presented as CE1 (50%) and CE3B (42%) images according to WHO ultrasound classification. Both males and females were infected with E. granulosus s.s but only the females showed infection with E. canadensis G6/7. Chi square test revealed significant difference between age of individuals and cysts classification by ultrasound. In addition, there was an association between cyst presentation (single or multiple) and genotype whereby all the E. canadensis G6/7 cases presented as single cysts in the infected persons. CONCLUSION: This study corroborates previous reports that E. canadensis G6/7 strain is present in Turkana, a place where initially only E. granulosus s.s (G1-G3) was known to be present and that E. granulosis (G1-G3) remains the most widespread genotype infecting humans in the Turkana community. PMID- 26862624 TI - AUDIT OF BLOOD TRANSFUSION PRACTICES IN THE PAEDIATRIC MEDICAL WARD OF A TERTIARY HOSPITAL IN SOUTHEAST NIGERIA. AB - OBJECTIVES: To determine the indications, practices and outcomes of transfusion on children. DESIGN: A descriptive retrospective study. SETTING: Paediatric wards of University of Nigeria Teaching Hospital, Enugu, Nigeria. SUBJECTS: Children one month to 18 years that received blood transfusion. MAIN OUTCOME MEASURES: Indications for the transfusion, haemoglobin rise, vital signs, duration of transfusion and adverse events. RESULTS: The two hundred and thirty eight transfusions reviewed were given amongst 95 patients, at a ratio of 2.5 transfusions per patient. The indicators of the transfusion were: malignancy (31.7%), sepsis (15.1%), sickle cell anaemia (12.1%), malaria (10.0%), hyperbilirubinaemia (10.0%), HIV/AIDS (8.3%), nephrotic syndrome (7.2%) and malnutrition (5.4%). Whole blood (56.4%) and sedimented cells (36.3%) were the main types of blood transfused. About 96.4% were transfused appropriate volume of blood. The mean Haemoglobin concentration (Hb) increase was 3.1g/dl and 12.8% of the recipients recorded an Hb increase of 5g/dl. The mean duration of transfusion was 4.6 hours and 59.7% of the transfusions exceeded the recommended four hours. Pulse and respiratory rates returned to normal post transfusion in 26.1 and 21.8% of the recipients respectively. In 10% of the transfusions there were minor adverse events; chills/fever (5.1%), itching (3.4%), hypothermia (1.0%) and vomiting (0.5%). CONCLUSION: Blood transfusion in this tertiary institution is not common and mainly due to non-communicable diseases. The expected optimal rise in Hb and normalising of vitals sign are not always the case. The duration of most transfusions was unduly prolonged and transfusion-related adverse events are rare. PMID- 26862623 TI - THE PROFILE AND UROLOGICAL SERVICE NEEDS OF OUTPATIENTS ATTENDING A TERTIARY CENTRE IN WESTERN KENYA. AB - BACKGROUND: Urological service needs cut across varied ages and related conditions. The outpatient attendance is a reflection of the common conditions constituting the urological burden of a given population (1). The urological burden in turn has implications on access to care and treatment (2) since it will determine the skills needed, mode of treatment, amount of time and other resources required to meet these needs. There is, therefore, a need to have a local data base on the profile of our urological patients and their needs with regard to modes of treatment. This study strives to and meets this important objective. OBJECTIVE: To establish the epidemiology of outpatient urology patients and their service needs as seen in a tertiary centre in the Western region of Kenya. DESIGN: Hospital based observational, descriptive, prospective, cross sectional study. SETTING: The Urology Outpatient clinic of Moi Teaching and Referral Hospital (MTRH), a 750 bed tertiary centre in the Western region of Kenya catering for approximately half of the Kenyan population. SUBJECTS: Ninety four first time attendees to the urology clinic seen in the year 2011. MAIN OUTCOME MEASURES: The primary outcome measures were the demographic data and diagnosis while the secondary outcome measure was the urological service needs of the patients in terms of treatment as to whether surgical or medical at presentation. RESULTS: Ninety-four patients attended the urology clinic for the first time in the year of study. The male to female ratio was 14.7: 1. Age ranged from one year to 97 years with a mean +/- standard deviation of 48.0 +/- 25.3 years. Half were below and half were above 50 years of age. Males had longer durations of symptoms compared to females but the difference was not statistically significant (p = 0.131). The top three urological problems were urethral strictures, prostate diseases and Urinary Tract Infections. There was an overall 70.2% need for surgical interventions with twenty-six point one percent of the prostate disorders being managed medically while all urethral strictures were planned for surgery. The odds ratio for surgery after one year compared to within first year of symptoms was two. CONCLUSION: The urological patients attending this tertiary outpatient clinic are predominantly males and are widely spread out in terms of age and diagnosis. The clinical burden of urethral strictures has overtaken that of prostate diseases in this tertiary centre. PMID- 26862625 TI - A COMPARATIVE STUDY ON THE EFFICACY OF TWO REGIMENS OF SINGLE- SHOT SPINAL BLOCK FOR PAIN RELIEF IN WOMEN PRESENTING IN ESTABLISHED LABOUR. AB - BACKGROUND: Most women experience moderate to severe pain during labour and delivery, often requiring some form of pharmacologic analgesia. The lack of proper psychological preparation combined with fear and anxiety can greatly enhance the patient's sensitivity to pain and further add to the discomfort. Skillfully conducted obstetric analgesia, in addition to relieving pain and anxiety, may benefit the mother by increasing self esteem and improving bonding with the baby. OBJECTIVE: To assess and compare the satisfaction and efficacy of two regimens of single-shot spinal blocks for the relief of labor pain in women who present in active phase of labour. DESIGN: A prospective randomised single blind observational study SETTING: Labour ward of Kenyatta National Hospital, Nairobi. SUBJECTS: All consenting primiparous women presenting in active phase of labor with uncomplicated singleton pregnancy at term (> 37 weeks) and in cephalic presentation, who reported a > 70 mm VAS (Visual Analog Scale) pain score at cervical dilatation >= 5 cm at the time of request for labour analgesia. RESULTS: Effective labour analgesia lasting up to 120 minutes was observed in the fentanyl bupivacaine group but with high incidence of breakthrough pain. The fentanyl bupivacaine-morphine group had labour analgesia lasting up to 180 minutes or even more with a lower incidence of breakthrough pain. The one-minute and five- minute Apgar scores in the morphine group were significantly lower (p = 0.026 and 0.044 respectively) than in the fentanyl group but the difference in neonatal outcome had no clinical significance, and there were no significant differences in adverse effects, sensory levels, and motor power between the two groups. CONCLUSION: Effective analgesia for about 120 minutes was observed in the fentanyl-bupivacaine group with high incidence of breakthrough pain while the fentanyl-bupivacaine-morphine group had labour analgesia prolonged up to more than three hours. The difference in fetal outcome had no clinical significance for the morphine group, and there were no significant difference in adverse effect, sensory levels, and motorpowerbetween the two groups. These findings show that intrathecal analgesia is safe and the use of the combination of fentanyl bupivacaine-morphine gives adequate and safe analgesia during labour and delivery. PMID- 26862626 TI - THE SIGNIFICANCE OF EPIDERMAL GROWTH FACTOR RECEPTOR AND SURVIVIN EXPRESSION IN BLADDER CANCER TISSUE AND URINE CYTOLOGY OF PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF THE URINARY BLADDER. AB - OBJECTIVE: To assess whether epidermal growth factor receptor (EGFR) and survivin immunostaining of tumour cells in urinary cytology and tissue of patients with bladder cancer has a prognostic significance. DESIGN: Prospective study SETTING: Department of Surgery (Division of Urology), Mubarak Al-Kabeer Teaching Hospital and Faculty of Medicine, Kuwait University, Kuwait SUBJECTS: Urine cytology smears obtainedpriorto cystoscopy in patients with transitional cell carcinoma (TCC) of the bladder were immunostained for EGFR and survivin. Bladder cancer tissue resected at surgery was also immunostained for EGFR and survivin expression. Tissue expression of EGFR and survivin in TCC of the bladder was compared to their expression in urine cytology and relationship to tumour grade and stage. RESULTS: 178 patients were studied (43 newly diagnosed bladder cancer, 58 with recurrent TCC and 77 in disease remission). Twenty five patients with normal urothelium served as controls. The mean sensitivity of urine cytology, tissue survivin immunohistochemistry (IHC) and tissue EGFR IHC was 30.5%, 62% and 59% respectively. The corresponding mean specificity was 95%, 79% and 38% respectively. For grades 1, 2 and 3 bladder tumors, tissue expression positivity for EGFR was 47.8%, 92.9%, 100% and for tissue survivin it was 27.8%, 18.2% and 33.3% respectively. For grades 1, 2 and 3 bladder tumors, urine expression positivity for EGFR was 35.7%, 40% and 67.7% and for urine survivin it was 8.3%, 42.9% and 33.3% respectively. CONCLUSION: Positive EGFR immunostaining of urine cytology specimen or tumour tissue increases with histological grade of TCC of the bladder. Survivin expression is less consistent in both urine cytology specimen and tissue samples. EGFR immunostaining may provide a useful tool in the grading of bladder TCC and aid in the selection of patients that may benefit from administration of EGFR inhibitors. PMID- 26862627 TI - PREVALENCE OF RHEUMATIC HEART DISEASE AMONG PRIMARY SCHOOL PUPILS IN MID-WESTERN NIGERIA. AB - OBJECTIVE: To determine the prevalence of RHD among primary school pupils in Egor Local Government Area (LGA) of Edo State of Nigeria. DESIGN: A cross sectional study SETTING: The study was carried out among selected primary pupils in three public and six private schools in Egor LGA, (the smallest governmental unit) in mid-Western Nigeria. SUBJECTS: Using a multistage sampling technique, pupils were selected from public and private primary schools in Egor LGA. They were clinically screened for evidence of RHD by auscultating for significant murmurs. The pupils with significant murmurs then had echocardiographic evaluation to confirm the presence of RHD. MAIN OUTCOMES: Pupils with significant murmurs and pupils with echocardiographically confirmed RHD. RESULTS: Of the 1764 pupils recruited, 900 (51.02%) were females while 864 (48.98%) were males. The mean age of the pupils was 8.86 +/- 2.14 years. 1065 (60.37%) and 699 (39.63%) respectively were recruited from public and private schools. Of the 1764 pupils, six (0.34%) had significant murmur. Only one of the six had RHD, giving a prevalence of 0.57/1000 pupils. The pupil with RHD was a male, from public school and in the low socioeconomic class. CONCLUSION: The prevalence of RHD in this study is low compared to similar studies conducted outside the country. The true prevalence may be underestimated since higher prevalence is obtained from echocardiographic based screening compared to clinical screening. PMID- 26862628 TI - BILATERAL ORBITO-OCULAR GUNSHOT INJURY IN A NIGERIAN MALE: CASE REPORT AND REVIEW OF LITERATURE. AB - Orbito-ocular injuries with retained intra-orbital foreign bodies affecting both orbits are uncommon in civilian practice. This case report aims to highlight an unusual presentation of bilateral orbito-ocularinjury with retained intra-orbital foreignbodies following accidental explosion of a locally fabricated dane gun. A 30-year-old male presented with a five day history of bilateral orbito-ocular injury sustained following an explosion of a dane gun he was fabricating. There was immediate loss of vision in both eyes, and initial treatment was sought at a nearby private general medical clinic. Visual acuity at presentation was no perception of light and light perception with inaccurate projection in the right and left eye respectively, and he had an open wound over the left cheek with retained intra-orbital foreign bodies on plain radiographs. He subsequently underwent wound exploration and closure with removal of the foreign bodies. Vision however remained poor and he was lost to follow-up after being referred for vitreo-retinal consultation. The attendant socio-economic impact on the individual and family following severe bilateral orbito-ocular injury could be enormous when it results in bilateral loss of vision in a young adult. Measures should thus be put in place to regulate the handling of firearms so as to possibly reduce the resultant morbidity from such injuries. PMID- 26862629 TI - PREDICTORS OF C-REACTIVE PROTEIN RESPONSE IN CHILDREN INFECTED WITH PLASMODIUM FALCIPARUM MALARIA. AB - OBJECTIVE: To assess the predictors of C-reactive protein response in plasmodium falciparum malaria as seen in children in a malaria endemic region of Nigeria. DESIGN: A prospective cross-sectional study. SETTING: The Children Out-patient (CHOP) Clinic, Children Emergency Unit (CHEU), Child Welfare/Growth Monitoring Clinic, Immunisation Centre and Paediatric Ward of the University of Uyo Teaching Hospital (UUTH), Uyo in Akwa-Ibom State. SUBJECTS: Three hundred and sixty children aged six to sixty months with microscopically confirmed P. falciparum malaria compared with 360 healthy children without malaria parasitaemia matched for age and gender. RESULTS: The predictors of the C-reactive protein response in malaria (CRP >= 10mg/l) were fever (t = 6.867; p = 0.001), malaria parasite count (t = 5.387; p = 0.001), severe anaemia (t = -11.23; p = 0.001) and age. Younger children had a greater CRP response. The logistic regression curve showed a 66.9% sensitivity, 92.1% specificity, positive predictive value, 83.2% and negative predictive value of 82.2% of predicting C-reactive protein response in malaria. CONCLUSION: P. falciparum malaria induces significant CRP responses. Younger children who present with fever, hyperparasitaemia and severe anaemia are more likely to have C-reactive protein response with malaria. PMID- 26862630 TI - PREVALENCE OF ACUTE MALNUTRITION IN PRE-SCHOOL CHILDREN IN A RURAL AREA OF NORTHERN SUDAN. AB - OBJECTIVES: To determine the prevalence of acute malnutrition in pre-school children in Karma Albald village, Northern Sudan. DESIGN: Prospective observational study. SETTING: Four kindergartens in Karma Albald village, Northern Sudan. SUBJECTS: Pre-school children attending kindergartens in Karma Albald village (n = 163). RESULTS: Using the World Health Organization case definitions and weight-for-height growth chart, wasting was observed in 29 of 163 children (17.8%); nine children had severe wasting. Socio-economic data showed that 70 children (43%) were from large families (families with four or more children) and 40 were from 'poor' families; 21 fathers and 12 mothers had poor literacy. All of the risk factors associated with malnutrition that were studied (that is, economic status, family size, order of the child in the family, and other socio-economic indicators) did not reach statistical significance. CONCLUSIONS: The prevalence of malnutrition was high in this cohort. Effective interventions are needed to tackle this major child health problem. PMID- 26862631 TI - ADHERENCE TO PNEUMONIA GUIDELINES FOR CHILDREN 2 - 59 MONTHS AT GARRISA PROVINCIAL GENERAL HOSPITAL. AB - BACKGROUND: Clinical Practice Guidelines for childhood illnesses including pneumonia in Kenya are contained in the Ministry of Health Basic Paediatric Protocols. In the presence of a cough and/ or difficulty in breathing and increased respiratory rate for age, pneumonia is diagnosed. In addition to these the presence of lower chest wall indrawing denotes severe pneumonia; The presence of cyanosis, inability to drink/ breastfeed, grunting, level of consciousness using the AVPU scale less than A in addition to the aforementioned is classified as very severe pneumonia. Recommended management is intravascular Crystalline penicillin, gentamycin and oxygen for severe pneumonia, intravascular crystalline penicillin for severe pneumonia and oral amoxyl or cotrimaxole for pneumonia. These guidelines have been disseminated through the Emergency Triage And Treatment Plus (ETAT +) coursesheld since 2007. Implementation of guidelines into care has been shown to reduce case fatality from pneumonia by 36%. OBJECTIVES: To evaluate the level of adherence and factors affecting adherence to the National guidelines on management of pneumonia in children aged two to fifty nine months at Garissa provincial General Hospital, Kenya. DESIGN: Retrospective hospital based cross sectional study. SETTING: Paediatric Department of Garissa Provincial General Hospital (PGH) in Kenya. SUBJECTS: Hospital medical records of children aged two to fifty nine months diagnosed with pneumonia between January and June 2012 were reviewed. Data abstracted from the records included demographic information, recorded clinical signs and symptoms, disease classification and treatment. RESULTS: Records of 91 childrenwere reviewed. Theirmedian age was 12 months (IQR 6 - 18 months). There were more boys than girls with a male to female ratio of 1.25:1. Forty-eight of the participants (52.8%) had severe pneumonia. Guideline adherence was assessed at three levels; assessment of clinical signs and symptoms reflected by their recording, correct disease severity classification and correct treatment prescribed. There were a minimum of two and a maximum of six clinical sign and symptoms recorded. The average level of adherence was 42.9% (SD +/- 17.3).Documented correct classification of disease severity was 56.6% and recommended treatment of pneumonia was 27.7%. The presence of a co-morbidity and severe disease was associated with better adherence to the assessment tasks (p = 0.033 and p = 0.021 respectively). Disease severity was associated with better adherence to the disease classification task (p = < 0.001) and treatment task (p = 0.02). CONCLUSION: Adherence to guidelines was low at all assessed levels. Overall, disease severity was associated with better guideline adherence. Presence of co-morbidities improved disease assessment. PMID- 26862632 TI - MALARIA PARASITAEMIA AMONG FEBRILE CHILDREN INFECTED WITH HUMAN IMMUNODEFICIENCY VIRUS IN THE CONTEXT OF PROPHYLACTIC COTRIMOXAZOLE AS STANDARD OF CARE: A CROSS- SECTIONAL SURVEY IN WESTERN KENYA. AB - OBJECTIVE: To document the prevalence of malaria parasitaemia among the HIV infected febrile children in a malaria endemic area. DESIGN: A cross-sectional study. SETTING: An ambulatory paediatric HIV clinic in Western Kenya, between November 2011 and December 2012. SUBJECTS: A total of 245 febrile HIV infected children aged less than 14 years attending the HIV clinic in the Webuye level IV hospital were included in the study. A systematic sampling method was used. MAIN OUTCOMES: A blood sample was taken for malaria parasite testing. Presence or absence of malaria parasites was documented. Clinical and socio-demographic characteristics of the participants were also recorded. RESULTS: A total of 245 participants were recruited mean age being 5.53 years. Malaria prevalence was 81.9%. Most participants (97%) were on cotrimoxazole prophylaxis. Some of the factors found to be positively associated with malaria parasitaemia were; male sex, care taker category (parent), WHO stage 3 and 4 of HIV disease, and a high absolute CD4 count. However, only the caretaker association was statistically significant. CONCLUSION: The frequency of malaria parasitaemia among febrile HIV infected children is still high regardless of the high cotrimoxazole prophylaxis uptake. It is also noted that there is a shift in the age group of fever among children toward the older age group. This implies that policies may need to be relooked at to include the older age group in the aggressive malaria prevention measures to avoid losing on the already made gains. PMID- 26862633 TI - THE EFFECT OF CD4 COUNT LEVEL ON THE MIDDLE EAR DYNAMICS OF HIV INFECTED PATIENTS. AB - BACKGROUND: HIV infection, a multi systemic disease has been identified as one of the causes of hearing loss in man. OBJECTIVES: To compare the effect of HIV infection on the middle ear dynamics of HIV infected and non-HIV infected individuals using tympanometry. DESIGN: A prospective cross sectional study. SETTING: HIV Clinic at University of Benin Teaching Hospital (UBTH) in 2010. SUBJECTS: Tympanometry was done on adults (18-45 year old) patients with confirmed retroviral disease (RVD) infection and confirmed non-HIV infected adults (18-45 year old) as the control group. All the patients certified the inclusion and exclusion criteria. MAIN OUTCOME MEASURES: More women were found with HIV infection than men at a ratio of 1:3.7(men = 21% and females = 79%). There was preponderance of type "B" tympanogram among HIV-infected individuals. RESULT: There was a significant correlation between CD4 cell count and type "B" tympanogram (P = 0.03). The CD4 cell count measured severity of HIV infection while the type "B" tympanogram detected middle ear effusion. CONCLUSIONS: Middle ear effusion is the genesis of middle ear pathology in HIV infected population. PMID- 26862634 TI - EFFECTS OF ENTERAL GLUTAMINE SUPPLEMENTATION ON REDUCTION OF INFECTION IN ADULT PATIENTS WITH SEVERE BURNS. AB - OBJECTIVE: To determine the effect of enteral glutamine in reducing the incidence of post burn infections in patients with severe burns. DESIGN: A double blind randomised clinical trial. SETTING: Burns unit and ward 4D of Kenyatta National Hospital, Kenya. SUBJECTS: Sixty patients with severe burns who were randomised to two arms of treatment: (1) the glutamine group and (2) isonitrogenous arm acting as the control. RESULTS: Patients' demographic and baseline clinical characteristics were similar in both arms of treatment. For the entire four-week treatment period, the odds ratio of a positive blood culture was almost three fold higher among patients in the control group compared to those in the Glutamine group (p = 0.04). There was also a higher incidence of positive swab cultures from the non glutamine group. CONCLUSION: Enteral glutamine supplementation in severely burnt adult patients reduces blood infection by a factor of three. It also significantly reduces the incidence of burn wound infections. PMID- 26862635 TI - ASSOCIATION BETWEEN FINGER CLUBBING AND CHRONIC LUNG DISEASE IN HIV INFECTED CHILDREN AT KENYATTA NATIONAL HOSPITAL. AB - BACKGROUND: Finger clubbing in HIV infected children is associated with pulmonary diseases. Respiratory diseases cause great morbidity and mortality in HIV infected children. OBJECTIVE: To determine association between finger clubbing and chronic lung diseases in HIV infected children and their clinical correlates (in terms of WHO clinical staging, CD4 counts/percentage, anti-retroviral therapy duration and pulmonary hypertension). DESIGN: Hospital based case control study. SETTING: The Kenyatta National Hospital (KNH) comprehensive care clinic (CCC) for HIV infected children and Paediatric General Wards. SUBJECTS: The study population comprised of HIV infected children and adolescents aged eighteen years and below. RESULTS: Chronic lung disease was more common among finger clubbed (55%) than non finger clubbed patients (16.7%). Finger clubbed patients had higher risk of hypoxemia (46.7%), pulmonary hypertension (46.7%) and advanced disease in WHO stage III/IV (91.7%) compared to non-finger clubbed patients. Finger clubbed patients had lower CD4 cells count and percentage (median 369 cells, 13%) compared to non-clubbed patients (median 861 cells, 28%). Duration of ART use was shorter in finger clubbed patients (median 5.5 months) compared to non-finger clubbed patients (median 40 months). CONCLUSION: Presence of finger clubbing in HIV infected children was associated with chronic lung disease, advanced WHO stage, lower CD4 counts/ percentage, shorter duration of ART use and higher likelihood of developing pulmonary hypertension. PMID- 26862636 TI - GROWTH AND NUTRITIONAL STATUS OF THE FIRST SIX MONTHS OF LIFE AMONG SELECTED HOSPITALS--NAIROBI PROVINCE. AB - BACKGROUND: Exclusive breastfeeding for infants is recommended for the first six months for optimal health, development and growth. However, there is limited data on infant feeding practices and nutrition status of infants in Nairobi. OBJECTIVE: To assess infant growth and nutritional status and compare with feeding practices in the first six months of life in selected hospitals, Nairobi Province. DESIGN: Prospective cohort design SETTING: Five major hospitals in Nairobi namely; The Aga Khan, Pumwani Maternity, Mater Misercordiae, St Mary's Langata and Jamaa Hospitals. SUBJECTS: A sample of 692 mother-infant pairs were recruited at birth and followed up until six months. INTERVENTION: There was no direct experimental intervention, but there was observation of infant feeding practices, weight and height measurement was recorded every four weeks and determination of nutrition status of the infants for a period of six months. MAIN OUTCOME MEASURES: Nutritional status and infant feeding practices in the first six months. RESULTS: Slightly more than half (58.8%) of the mothers were formally employed and the rest were self employed. The mean age of the mothers was 28.3 +/ 4.9 years. The mean income was KES 26,360 +/- 34,696. The mean birth weight of infants was 3.24 +/- 0.43 kg and 53.3% of all infants were male. Above 80% of infants were within normal weight based on weight for age Z-scores (WAZ) at 6, 10, 14 and 23 weeks. The prevalence of overweight based on WAZ was 9.5%, 11.6%, 11.9% and 11% at 6, 14, 19 and 23 weeks, respectively. There were no significant (P > 0.05) differences in WAZ between infants on different feeding methods. CONCLUSIONS: There was no significant difference in weight or length gain among children that were fully breastfed in comparison to those who were given infant formula or had mixed feeding. However, there was concern over the proportion of overweight infants, as the condition may lead to long term health problems. PMID- 26862637 TI - A COMPARATIVE ANALYSIS OF FIRST DAY NEONATAL MORTALITY BETWEEN ADOLESCENTS AND ADULT FEMALES GIVING BIRTH AT LIGULA HOSPITAL IN MTWARA, SOUTH EASTERN TANZANIA 2008-2009. AB - OBJECTIVE: Compare first day neonatal mortality between adolescents and adults delivering at the main referral hospital in Mtwara, Tanzania DESIGN: Cross sectional chart review SETTING: The study was conducted at the main referral hospital in Mtwara, Tanzania. Rates of adolescent pregnancy at the hospital were 15.5% in 2009 and 14.3% in 2010 SUBJECTS: A total of 450 adolescent and adult females delivering at Ligula Hospital between 2008 and 2009 were included in the study. OUTCOME MEASURES: First day neonatal mortality between adolescents and adults was the primary outcome. Secondary outcomes included neonatal birth weight, parity, gravidity, prematurity, HIV and neonates delivered. RESULTS: First day neonatal mortality was 5.56%. Birth weight was the only risk factor significantly associated with neonatal mortality CONCLUSION: Younger women have predisposal to neonatal mortality due to underlying causal mechanisms. In order to validate the results of this study, further research on risk and causes of first day neonatal mortality at facilities is warranted. PMID- 26862638 TI - FACTORS ASSOCIATED WITH UPTAKE OF SKILLED ATTENDANTS' SERVICES DURING CHILD DELIVERY IN GARISSA TOWN, KENYA. AB - OBJECTIVE: To identify the factors that are associated with uptake of skilled delivery services during child delivery among women of reproductive age in Garissa town. DESIGN: Cross sectional study. SETTING: Garissa town. SUBJECT: Three hundred and thirty four women aged 15-49 years who had had at least one delivery in their lifetime were asked about the type of delivery services they had during their last child delivery. RESULTS: The study found that 47% of the last deliveries women were attended by skilled persons and the rest of the deliveries were provided by TBAs. The predictors of skilled delivery uptake in this study were found to be; having knowledge on skilled delivery service providers (AOR = 17.2; 95% CI: 1.05-281.12; p = 0.046), child deliveries numbering one to three (AOR = 116.95; 95% CI: 26.68-512.64; p = 0.001) and four to six (AOR = 16.75; 95% CI: 4.44-62.87; p = 0.001), presence of previous delivery complication (AOR = 11.71; 95% CI: 3.96-34.60; p = 0.001), disapproval of TBA services (AOR = 27.19; 95% CI: 6.67-110.76; p = 0.001), lack of preference for gender of skilled delivery service provider (AOR = 6.51; 95% CI: 1.08-39.37; p = 0.041), and positive view on service related factors such as time to nearest facility (AOR = 3.91; 95% CI: 1.24-12.34; p = 0.020), hygiene (AOR = 5.03; 95% CI: 1.49-17.05; p = 0.009) and operation time of health facility (AOR = 4.67; 95% CI: 1.59-13.76; p = 0.005). CONCLUSSION: The findings show that cultural and maternal factors as well as quality of services at facility level play major role in determining uptake of skilled services among women in Garissa as compared to social demographic and economic factors. PMID- 26862639 TI - SCROTAL RECONSTRUCTION WITH A PEDICLED GRACILIS MUSCLE FLAP AFTER DEBRIDEMENT OF FOURNIER'S GANGRENE: A CASE REPORT. AB - As part of surgical management of Fournier's gangrene, multiple and extensive debridement of necrotic tissue is done which results in significant loss of scrotal skin and exposure of testes. This necessitates reconstruction of a neoscrotum to cover of the testes. Several scrotal reconstructive options are available including split thickness skin grafts, scrotal advancement flaps, local fasciocutaneous, muscle or myocutaneous flaps, and free tissue transfer. We report a case of a 34 year old African male who presented as a referral from a district hospital with a scrotal defect and exposed testes following extensive debridement of Fournier's gangrene. Scrotal reconstruction with a pedicled gracilis muscle flap was done. The pedicled gracilis muscle flap is close to the scrotal area and is ideal for coverage of large scrotal defects with deep pockets. It is well vascularised thereby providing greater resistance to infection, a good bed for skin grafting yet eliminating the risks associated with potentially non reliable skin paddle in the myocutaneous flap. PMID- 26862640 TI - CD4 T-LYMPHOCYTE SUBSETS IN WOMEN WITH INVASIVE CERVICAL CANCER IN KENYA. AB - OBJECTIVE: Invasive cervical cancer (ICC) and HIV are common in sub-Sahara Africa. Both ICC and HIV are immunosuppressive, and are associated with decreased CD4 and CD8 profiles. In a group of women with ICC starting radiotherapy, we determined their CD4 profiles. DESIGN: A cross-sectional study. SETTINGS: Kenyatta National Hospital, Nairobi, Kenya, radiotherapy unit. SUBJECTS: Women with invasive cervical cancer (344) seeking radiotherapy treatment for the first time between January 2000 and March 2003, had blood samples analyzed for CD4 and CD8 cell counts by flow cytometry. Haemoglobin, white cell count, lymphocyte and platelet counts were determined using coulter machine. All patients had received pre- and post HIV counseling. RESULTS: The mean age was 49+13 years. About 13.1% of the women with ICC were HIV positive. Overall, mean and median CD4 cell count was 829+355 cells/mm and 792 cells/mm3. Among HIV+ patients, mean and median CD4 cell counts were 451+288 cells/mm and 405 cells/mm respectively. The mean CD4 cell count for the HIV+ womenwas 886+329 cells/mm3 with median of 833 cells/mm3, range 147-2065 cells/mm3. Only nine (20%) of the 45 HIV+ women had CD4 cell count of 0-200. HIV+ women had lower CD4 percentage and cell count and higher CD8 percentage and cell count as compared to HIV negative women, p < 0.001. HIV infection was significantly and independently associated with high proportion of women who had CD4 cell count of less than 200 cells/mm3 or less than 350 cells/mm3, p < 0.0001. CONCLUSIONS: Women with ICC and concurrent HIV infection have decreased CD4 cell subset. These results suggest HIV infection may be associated with more severe CD4 depletion in women with ICC. PMID- 26862641 TI - CRYOTHERAPY FOLLOWING VISUAL INSPECTION WITH ACETIC ACID AND LUGOL'S IODINE (VIA/VILI) IN KHWISERO, WESTERN KENYA: LESSON FROM THE FIELD AFFECTING POLICY AND PRACTICE. AB - BACKGROUND: Cervical cancer can be prevented and mortality/morbidity reduced by early detection and referral. Developing countries are likely to benefit from more cost effective methods of screening and treatment. Visual inspection with acetic acid and Lugol's iodine (VIA/VILI) offers a see and treat solution thus an affordable and efficient way to identify pre-malignant lesions. Immediate treatment with cryotherapy can be offered if pre-malignant lesions are found on visual inspection. Cryotherapyis a simple procedure that is curative for dysplasia; it is likely to benefit cervical dysplasia cases picked early in resource poor settings, however there are several factors that hinder patients' access to this noble technique. OBJECTIVE: Determine hindrances to cryotherapy for patients following positive results of VIA/VILI after referral. DESIGN: Cross sectional Study SETTING: Khwisero, Western Kenya. SUBJECTS: Women attending a medical camp, willing to get screened for cervical cancer. RESULTS: One hundred and nine patients were screened; seventy three (66.97%) were negative for VIA/VILI, twenty one (19.26%) were positive and referred for cryotherapy. Reasons for lack of follow up were financial constraints, lack of medical personnel at referral centres and poor access to the referral facilities.19.26% of women identified with positive lesions required intervention. No patient received cryotherapy following referral. CONCLUSION: There is urgent need for availability of cryotherapy machines and training of personnel who can perform cryotherapy at the primary care level. Regional studies on knowledge attitudes and practices about VIA/VILI and cryotherapy are required to provide reasons for the poor uptake of this procedure. PMID- 26862642 TI - CHOLERA EPIDEMIOLOGY IN ZAMBIA FROM 2000 TO 2010: IMPLICATIONS FOR IMPROVING CHOLERA PREVENTION AND CONTROL STRATEGIES IN THE COUNTRY. AB - OBJECTIVE: To review the cholera epidemiology in Zambia from 2000 to 2010 in order to highlight the key lessons learned. Based on our findings, we make recommendations for improving cholera prevention and control in country. DESIGN: Ten years descriptive cholera data was extracted from the national IDSR database and analysed. SETTING: The study was conducted in Zambia using national epidemiology data which were disaggregated by Province. SUBJECTS: None. RESULTS: Starting from 2003, there has been a progressive increase in yearly incidence of cholera in the country. In 2010, 6794 cases (500% increase compared to 2003) and 115 deaths (CFR 1.6%) of the disease were reported with Lusaka Province accounting for 85% of the total cases. Outbreaks start between epidemiological weeks 40 to 45 of the year and ends between weeks 20 to 25 of the following year (which corresponds to the Zambian rainy season). Outbreaks are largely confined to the peri-urban areas of Lusaka, Luapula, Southern and Copperbelt Provinces. CONCLUSION: In the last 10-20 years, the epidemiology of cholera in Zambia has changed; Laboratory confirmation of Vibrio cholerae in the country on a yearly basis in the last ten years suggests that the country is now endemic for cholera hence the need to review current cholera prevention and control strategies. PMID- 26862643 TI - THE PREVALENCE OF POST-TRAUMATIC STRESS DISORDER AMONG SEXUALLY ABUSED CHILDREN AT KENYATTA NATIONAL HOSPITAL IN NAIROBI, KENYA. AB - BACKGROUND: Post-Traumatic Stress Disorder (PTSD) develops following some stressful events. There has been increasing recognition that children who have been exposed to traumatic events like child sexual abuse can develop post traumatic stress disorder just like adults. OBJECTIVE: To determine prevalence of PTSD in sexually abused children seen at the Gender Based Violence Recovery Centre at Kenyatta National Hospital. DESIGN: A cross sectional descriptive study. SETTING: Gender Based Violence Recovery Centre-Kenyatta National Hospital. Subjects One hundred and forty-nine (n =149) sexually abused children were recruited in the study. RESULTS: The mean age 14.8% boys and 85.2% girls was 13.2 years (SD 4.2) the age at which sexual abuse most frequently (55%) occurred between 15-17 years. Sixty three percent of children reported that the perpetrator was known to them, and 76.5% of perpetrators used verbal or physical force during sexual assault. The prevalence of PTSD among the sexually abused children was 49%. PTSD was significantly associated with shorter duration of sexual abuse, i.e., daily which is 67% as compared to months which is 4.7% (p = 0.005), Greater severity of injuries sustained during assault (p = 0.023), parent's marital status those whose parents were married or cohabiting 40% were affected as compared to 52% whose parents were separated or divorced (p = 0.003) and the family's way of sorting out their disagreements was also significantly associated with PTSD. Parents who sorted their disagreement by talking was at 31% while those who sorted their disagreement by fighting was at 67% (p < 0.001). CONCLUSIONS: This study highlights the high prevalence of PTSD among sexually abused children presenting at Kenyatta National Hospital Nairobi-Kenya. PTSD is associated with the degree of physical or verbal abuse during sexual abuse, injuries during assault, and parent-child relationships. These findings are important in formulation of appropriate prevention and care interventions to be implemented by families and other stakeholders. PMID- 26862644 TI - ANAESTHETIC CHALLENGES IN A HIGH RISK PARTURIENT WITH MYASTHENIA GRAVIS UNDERGOING CAESAREAN SECTION UNDER SPINAL ANAESTHESIA. AB - The prevalence of myasthenia gravis is low. The management implications of this disease in pregnant women are very challenging for anaesthetists. The objective is to highlight some of the challenges, the management and the lessons learnt during the management of this patient. This is a case report of a 31-year old parturient with diagnosed myasthenia gravis co-existing with hepatitis B infection that presented for caesarean section. Surgery was carried out under a single-shot spinal anaesthesia with bupivacaine. Intraoperative myasthenia crisis was managed with neostigmine infusion. She was managed in the Intensive Care Unit for a few days and discharged. Under spinal anaesthesia, she became very breathless and developed wide-spread musculo-skeletal weakness while having a stable haemodynamics intra-operatively. Surgery was carried out successfully. Both mother and child were discharged on the 71th day post-operative after baby was confirmed sero-negative of hepatitis B surface antigen. A better understanding of the pathophysiology and complications that accompany myasthenia gravis is needed to manage these patients under anaesthesia. PMID- 26862645 TI - LIVER FUNCTION MARKERS AND ASSOCIATED SERUM ELECTROLYTES CHANGES IN HIV PATIENTS ATTENDING PATIENT SUPPORT CENTRE OF JARAMOGI OGINGA ODINGA TEACHING AND REFERRAL HOSPITAL, KISUMU COUNTY, KENYA. AB - OBJECTIVE: To determine the distribution of markers of liver function disorders and their association with co-existing fluids and electrolytes states in ambulatory HIV infected individuals. DESIGN: A case-control study. SETTING: Jaramogi Oginga Odinga Teaching and Referral Hospital's Patient Support Centre. INTERVENTION: Biochemical analysis were performed for serum alanine aminotranferase (ALT), aspartate-amino transferase (AST), total protein, albumin, glucose, urea, potassium, sodium, chloride, creatinine phosphate, total and direct bilirubin levels as well as CD4 lymphocyte levels. RESULTS: Serum liver function markers were significantly altered in HIV infected individuals compared to uninfected individuals (mean serum aspartate-amino transferase (AST); 45.1 U/l v/s 36.9 U/l; alanine-aminotransferase (ALT), 36.5U/l v/s 30.7 U/l; direct bilirubin, 4.9 micromol/l v/s 4.2 micromol/l; total bilirubin, 6.2 micromol/l v/s 5 micromol/l; albumin32.8 g/l v/s 34.3 g/l and protein 64 g/l vls 67.1 g/l; p <0.0001). The prevalence of pathological levels of serum liver function markers was also higher in HIV-infected patients than HIV-negative participants (ALT, 4.4% v/s 0.7%, p=0.001; AST, 24.5% v/s 6.7%, p<0.0001; direct bilirubin, 43.1% v/s 36.5%, p=0.026; total bilirubin, 2.3% v/s 0%, p=0.002; serum albumin, 60.1% v/s 52.2%, p= 0.009 and serum total protein levels, 52.8% v/s 36%, p<0.0001). Gender, age and anti-retroviral treatment were not predictors of aberrations in levels of liver function markers in HIV infected patients. Marked CD4 depletion was associated with enhanced deterioration of liver function markers. Liver function anomalies did not conduce co-existing electrolyte anomalies as clinically altered ALT states only correlated and co-varied with AST states (r = 0.917); direct biliribun states co-varied with total bilirubin levels (r = 0.958) and serum album states correlated with protein levels (r = 0.917) and vice versa. CONCLUSION: Liverfunction disorders are not infrequent in HIV infected individuals and routine review of liver health status is essential in comprehensive care of HIV patients. PMID- 26862646 TI - EFFECT OF LIGHT CURING UNIT CHARACTERISTICS ON LIGHT INTENSITY OUTPUT, DEPTH OF CURE AND SURFACE MICRO-HARDNESS OF DENTAL RESIN COMPOSITE. AB - BACKGROUND: Modern dental composite restorations are wholly dependent on the use of Visible Light Curing devices. The characteristics of these devices may influence the quality of composite resin restorations. OBJECTIVE: To determine the characteristics of light curing units (LCUs) in dental clinics in Nairobi and their effect on light intensity output, depth of cure (DOC) and surface micro hardness (SMH) of dental resin composite. DESIGN: Laboratory based, cross sectional analytical study. SETTING: Public and private dental clinics in Nairobi, Kenya. SUBJECTS: Eighty three LCUs which were in use in private and public dental health facilities in Nairobi, Kenya and resin composite specimens. RESULTS: Of the 83 LCUs studied, 43 (51.8%) were Light Emitting Diodes (LEDs) and 39(47.0%) were Quartz-Tungsten-Halogen (QTH) and 1 (1.2%) was Plasma Arc Curing (PAC) light. Mean light intensity for QTH and LED lights was 526.59 mW/cm2 and 493.67 mW/cm2 respectively (p=0.574), while the mean DOC for QTH lights was 1.71 mm and LED was 1.67 mm (p=0.690). Mean Vickers Hardness Number (VHN) for LED was 57.44 and for QTH was 44.14 (p=0.713). Mean light intensity for LCUs < or = 5 years was 596.03 mW/cm2 and 363.17 mW/cm2 for units > 5 years old (p=0.024). The mean DOC for the two age groups was 1.74 mm and 1.57 mm respectively (p=0.073). For SMH, the < or = 5 years and >5 years age groups gave a mean VHN of 58.81 and 51.46 respectively (p=0.1). On maintenance history, the frequency of routine inspection, duration since the last repair/replacement of a part or other maintenance activity and the nature of the last maintenance activity were determined and were not found to have influenced the light intensity, DOC and SMH. CONCLUSION: The LCU age has a statistically significant influence on its light intensity (p=0.024) while the type and maintenance history have no significant influence on its light intensity and composite DOC and SMH (p=0.574, p=0.690, p=0.713 respectively). PMID- 26862647 TI - CLINICAL FEATURES AND PATTERNS OF IMAGING IN CEREBRAL VENOUS SINUS THROMBOSIS AT KENYATTA NATIONAL HOSPITAL. AB - BACKGROUND: Cerebral venous sinus thrombosis (CVST) is an uncommon neurological deficit. It shows a wide range of clinical manifestations that may mimic many other neurological disorders and lead to misdiagnosis. Imaging plays a key role in the diagnosis. OBJECTIVE: To evaluate the clinical characteristics and patterns of neuroimaging findings in patients with radiologically confirmed CVST. DESIGN: A retrospective study. SETTING: Kenyatta National Hospital, a tertiary referral and teaching hospital in Nairobi Kenya. SUBJECTS: Fifty one patients treated for CVST in the hospital were studied. RESULTS: Fifty one patients with CVST were seen over the last five years. The median age of 30 years. The most common age group affected was 25-34 years. Females were more affected (n=38, 74.5%) than males (n=13, 25.5%). The most common presenting clinical features documented were headache, seizures and neurological deficits. Aetiological factors commonly seen included infection (n=20, 39.2%), pregnancy and puerperium (n=7, 13.7%) and oral contraceptive use (n=2, 3.9%). The most common NECT scan findings were hyperdense sinus and parenchymal changes. MRI showed loss of signal void in the sinus, gyral swelling and parenchymal signal change. CONCLUSION: CVST is most commonly seen in young adult females due to infection, pregnancy, puerperium and oral contraceptive use. The most common clinical finding in patients with CVST is headache, followed by seizures, neck pain, neurological deficits and visual disturbance. Infective cause is much more common in our population and other developed countries compared to the developed world. PMID- 26862648 TI - SOCIO-DEMOGRAPHIC FACTORS IN UNDER FIVE CHILDREN WITH ACUTE DIARRHOEA IN A TERTIARY HEALTH INSTITUTION IN NIGERIA. AB - OBJECTIVE: To determine the socio-demographic factors in under five children with acute diarrhoea. DESIGN: A prospective cross-sectional study. SETTING: Children's Emergency Room and Children's Outpatient Clinic of the University of Nigeria Teaching Hospital, Enugu, Nigeria. SUBJECTS: One hundred and seventy-four children below five years of age. RESULTS: Between June 2005 and May 2006, one hundred and seventy-four children aged below five years with diarrhoea were recruited for the study. They were examined. Their socio-demographic factors such as age, sex, breastfeeding status, parents' occupation/education, were obtained. The following variables did not significantly affect the prevalence of diarrhoea: age (p>0.05), sex (p=0.233), breastfeeding (p=0.590), nutritional status (p=0.060), and socio-economic status (p=0.955). CONCLUSION: Socio-demographic factors did not appear to influence the prevalence of acute diarrhoea among under five children in Enugu, Nigeria. PMID- 26862649 TI - PREVALENCE, TREATMENT AND CONTROL OF HYPERTENSION AMONG TYPE 2 DIABETIC PATIENTS AT MOI TEACHING AND REFERRAL HOSPITAL, ELDORET, KENYA. AB - OBJECTIVES: To describe the prevalence, treatment and control of hypertension among type 2 diabetic patients at Moi Teaching and Referral Hospital (MTRH) and to determine predictors of blood pressure (BP) control. DESIGN: A cross-sectional study. SETTING: Diabetic Outpatient Clinic at MTRH, Eldoret, Kenya. SUBJECTS: Type 2 diabetic patients. INTERVENTIONS: The study collected socio-demographic (age, gender, employment status, monthly income, education level, marital status, cigarette smoking and alcohol use), clinical (BP, weight, height and waist circumference) and laboratory (serum fasting lipids and creatinine, urine proteins) data from type 2 diabetic patients. Good BP control was defined as < 130mmHg systolic and < 80mmHg diastolic. Association between BP control and social demographic, clinical and laboratory variables of study subjects was determined using the chi-square, T-test, fisher's exact test and logistic regression. RESULTS: We studied 218 type 2 diabetics: mean age 57 +/- 9 years; 122 (56%) were females. Average duration of diabetes was 11 +/- 7 years. Prevalence of hypertension was 185/218 (85%) out of who 40 (21%) had good BP control. Average duration of hypertension was 7 +/- 5 years. Of the 185 hypertensive diabetics: 92 (50%) had total cholesterol at goal; 102 (55%) had low density lipoproteins (LDL) at goal; 74 (40%) had triglycerides at goal; 65 (35%) had high density lipoprotein (HDL) at goal and 85(45%) had Proteinuria. All hypertensive patients had > 1 anti-hypertensive agent prescribed. Good BP control was associated with compliance to anti-hypertensives (OR = 0.342, 95% CI: 0.105- 1.432) and having HDL at goal (OR = 0.247, 95% CI: 0.126-0.845). Poor BP control was associated with a higher number of prescribed anti-hypertensive agents (OR = 1.377, 95% CI: 1.112- 2.302). CONCLUSION: Prevalence of hypertension among type 2 diabetic patients in MTRH is high and BP control is poor despite anti hypertensive treatment. Significant predictors of BP control include compliance to anti-hypertensives and control of HDL. PMID- 26862650 TI - IMMUNOLOGICAL PROFILES IN HIV POSITIVE PATIENTS FOLLOWING HAART INITIATION IN KIGALI, RWANDA. AB - BACKGROUND: Interleukin-10, IL-2 and IFN-gamma are some of the crucial cytokines associated with HIV infection and pathogenesis. While IL-2 and IFN-gamma play critical roles in host resistance to infection, IL-10 inhibits the synthesis IFN gamma, IL-2 at mRNA and protein level; exacerbating damage to immune system. OBJECTIVE: To determine the levels of, changes in and correlation between CD4 count, viral load, IL-10, IL-2 and IFN-gamma before HAART and at six months of HAART among HIV positive patients in Kigali; with a view to understand cytokine networks particularly in relation to HAART; and to see whether they can be used as alternative markers of the disease progression. DESIGN: Longitudinal study. SETTING: Kagugu, Kimironko, Biryogo, Gitega Health Centres and Centre Medico Social Cornum; all located in Kigali. SUBJECTS: Thirty three (33) HAART initiation eligible HIV positive patients including 13 women and 20 men. RESULTS: A drop in viral load (though only a small number of patients achieved an undetectable viraemia); a recovery of CD4+ cells, a decrease in IL-10 (though it remained high for many patients especially those with unchanged viraemia); and an increase in IL-2 and IFN-gamma indicated a successful HAART. A negative correlation between CD4 count and viral load and between CD4 count and IL-10 (but r < -0.5) was observed. IL-10 correlated positively and strongly with viremia (r > 0.5 at both time points: p-values < 0.05). There was no significant correlation between CD4 count, IL-2 and IFN-y. CONCLUSION: Results demonstrated the down regulatory effect of IL-10 on Th1 cytokines and that a shift from Th1 to Th2 cytokine is associated with HIV disease progression. A successful HAART results in CD4+ cells recovery, drop in viraemia and IL-10 with up-regulation of Th1 cytokines. Also, findings show potential usefulness of IL-10 as a marker of HIV disease progression. PMID- 26862651 TI - UPPER GASTROINTESTINAL ENDOSCOPY FINDINGS IN PATIENTS REFERRED WITH UPPER GASTROINTESTINAL SYMPTOMS IN ELDORET, KENYA: A RETROSPECTIVE REVIEW. AB - BACKGROUND: Dyspepsia is one of the major indications for upper gastrointestinal endoscopy. Other indications include dysphagia, odynophagia and gastrointestinal bleeding. Endoscopy is an expensive procedure that is out of reach of many patients in resource constrained region such as western Kenya. We reviewed endoscopy records from both public and private health institutions spanning ten years. OBJECTIVE: To determine the pattern of referral and endoscopy diagnoses in patients referred for upper gastrointestinal endoscopy in Eldoret, Kenya. DESIGN: Retrospective chart review. SETTING: Moi Teaching and Referral Hospital, private hospitals and private clinics in Eldoret, Kenya. SUBJECTS: One thousand six hundred and ninety (1690) Patients who underwent upper GI endoscopy from 1993 to 2003 were reviewed after obtaining clearances from the respective institutions. Information on age, sex, symptoms, and endoscopy diagnosis were extracted and subjected to statistical analysis. RESULTS: The most common symptom was dyspepsia in 1059 (62.7%) followed by dysphagia in 224 (13.3%). Others were referred with diagnosis of cancer of the stomach or oesophagus. Common endoscopy diagnoses were cancer of the oesophagus in 199 (11.8%) and duodenal ulcer in 186 (11.0%). The majority of the patients (30.4%) had normal endoscopy findings. Of the 1059 patients with dyspepsia, only 154 (14.5%) had duodenal ulcer and 34 (3.2%) had gastric ulcers, the majority, 37.2% had normal endoscopy findings. CONCLUSION: Dyspepsia was main reason for referral, but the majority of such patients had normal findings. Cancer of the oesophagus was the main diagnosis in patients with dysphagia. In view of the cost of endoscopy, only those with dyspepsia and alarm symptoms be referred for the procedure. PMID- 26862653 TI - ISOLATION AND CHARACTERISATION OF CRYPTOCOCCUS NEOFORMANS AND CRYPTOCOCCUS GATTII FROM ENVIRONMENTAL SOURCES IN NAIROBI, KENYA. AB - Objective: To establish the environmental reservoirs of Cryptococcus neoformans and Cryptococcus gattii in Nairobi, Kenya. Design: Prospective study. SETTING: Kenya Medical Research Institute, Mycology laboratory, Nairobi, Kenya. SUBJECTS: A total of 400 environmental samples from different sites were analysed including; avian droppings, tree swabs, soil contaminated with avian droppings and swabs from garbage damping sites. Samples were subjected to various phenotypic tests including microscopic morphology, physiological and biochemical tests, pigmentation on bird seed agar and reaction on Canavanine-Glycine Bromothymol Blue agar. RESULTS: Cryptococcus neoformans was isolated from 23/200 (11.5%) dropping samples and Cryptococcus gattii in 5/200 (2.5%) of the same samples. Cryptococcus gattii was isolated from 7/60 (11.7%) tree swabs and Cryptococcus neoformans in 5/60 (8.5%) of the same samples. From other sites there was no Cryptococcus gattii recovered with (5/50: 10%), (6/60: 10%), (2/30: 6.7%) Cryptococcus neoformans recovered from chicken cage, garbage damping site and soil respectively. CONCLUSION: Findings clearly showed a high presence of Cryptococcus neoformans and Cryptococcus gattii from several environmental sites in Nairobi, Kenya. This could probably explain the high incidence of cryptococcal meningitis in HIV/AIDS patients in Kenya. PMID- 26862652 TI - UMBILICAL CORD PARAMETERS IN ILORIN: CORRELATES AND FOETAL OUTCOME. AB - BACKGROUND: The anthropometric parameters of the umbilical cord have clinical significance. Current parameters of the cord, its correlates and related foetal outcome are lacking in our parturients. OBJECTIVES: To describe the anthropometric parameters and abnormalities of the umbilical cord; and determine their maternal correlates and foetal outcome. DESIGN: A cross sectional analytical study. SETTING: The Obstetric and Gynaecology Department of the Universityof Ilorin Teaching Hospital, between September 2012 and June 2013. SUBJECTS: Healthy pregnant women with singleton pregnancies. RESULTS: Four hundred and twenty-eight (428) singleton deliveries were studied. The respective mean values of the cord length and width were 526.87 +/- 115.5mm and 19.56 +/- 11.12mm.Short cord (< 40cm) occurred in 7.2% while long cord (> 69cm) was found in 9.3% of the parturient. The incidences of single umbilical artery, cord round the body and knots were 7%, 8.4% and 14.5% respectively. Nuchal cord was the most common (91.4%). Only gestational age had significant statistical relationship with cord length abnormalities (P = 0.0093). The cord length was an important correlate of cord helices, knots and vessels (P < 0.05).Parity had correlations with the number of vessels (R = 0.099, P = 0.042). The cord coiling index was statistically related to the presence of congenital abnormalities (P = 0.011). Other perinatal events were not related to umbilical cord parameters. Perinatal asphyxia was the most common indication for NICU admission (3.5%) but there was no significant statistical difference between NICU admission and cord parameters. CONCLUSION: The umbilical cord parameters in apparently healthy parturients in Ilorin were comparable with others elsewhere. The cord length and helix are important correlates of gestational age and congenital abnormalities. Parity may be related to abnormal umbilical vessels. Cord length, coils, coil index and umbilical vessels should be examined post-natally. PMID- 26862654 TI - AN ISOLATED SUPERIOR STERNAL CLEFT IN A NEONATE IN WESTERN KENYA: CASE REPORT. AB - Sternal cleft is a rare congenital anomaly and very few cases have been described especially in Africa. This is a case of an isolated superior sternal cleft in a term neonate in Western Kenya. PMID- 26862655 TI - UTILITY OF ROUTINE CHEST RADIOGRAPHS IN KENYA. AB - BACKGROUND: Many otherwise healthy Kenyans are required to obtain chest radiographs as part of routine medical examination to exclude pulmonary TB, a condition of significant public health concern. Many of these people are required to have these radiographs taken yearly as part of routine check-up. No local data is available to support this practice. Though a quick procedure to perform and readily available throughout the country, chest radiograph exposes the individual to a dose of ionising radiation. Ionising radiation is associated with increased risk of malignancy. The cost is also substantial. OBJECTIVE: To determine the prevalence of radiological findings consistent with PTB among routine medical examination chest radiographs. DESIGN: A cross-sectional descriptive study. SETTINGS: Department of Radiology Kenyatta National Hospital, Department of Imaging and Radiation Medicine, University of Nairobi, Plaza Imaging Solutions, a private radiology practice in Nairobi and Department of Radiology, the Nairobi Hospital. SUBJECTS: Four hundred and two chest radiographs of patients presenting for routine medical examinations were analysed. RESULTS: Sixty three radiographs had abnormal but clinically insignificant findings (16%). Only one radiograph (0.25%) had radiological features of PTB. The rest were reported as normal (84%). CONCLUSION: In this study, the diagnostic yield for the intended purpose (to include/ exclude PTB) was extremely low (0.25%). It is recommended that routine chest radiographs as screening tools for active pulmonary tuberculosis be reconsidered due to poor diagnostic yield. The authors propose a bigger nation wide study before a policy decision can be proposed. PMID- 26862656 TI - GROSS PRESENTATION AND HISTOMORPHOLOGICAL CHANGES OF PLACENTAE IN PATIENTS PRESENTING WITH INTRAUTERINE FOETAL DEATH AT KENYATTA NATIONAL HOSPITAL. AB - BACKGROUND: There are 3.2 million annual stillbirths, at least 98% occur in low /middle income countries, and on average, as many as two-thirds of these stillbirths are thought to occur antenatally, prior to labour. The most useful test towards a diagnosis after stillbirth is pathological examination of the placenta and the foetus. However, this pathological examination is done in less than half of the placentae after cases of stillbirth. OBJECTIVE: To determine gross presentation and histomorphological changes of placentae in patients presenting with intrauterine foetal death as compared to live births. DESIGN: A case control study. SETTING: The Kenyatta National Hospital's labour ward and the Department of Human Pathology, University of Nairobi. SUBJECTS: The cases were mothers who presented with IUFD at a gestation of 28 weeks and above. The controls were a comparative group of mothers who delivered live babies at the hospital and were matched for age. RESULTS: Reduction of the mass of functioning villi was present in 11.8% of placenta in the stillbirth group compared to 2% in the live birth group (p-value 0.002). There was significant presence of other placental abnormalities in the stillbirth group (22.5%) compared to the live birth group (9.8%) (p-value-0.002). CONCLUSION: This study revealed that histological examination of placenta is useful in identifying some causes of stillbirths. This knowledge may lead to preventive measures which would lower perinatal mortality. PMID- 26862657 TI - TETANUS NEARLY ELIMINATED AFTER 40 YEARS OF VACCINATION IN RURAL SENGEREMA DISTRICT, TANZANIA. AB - OBJECTIVE: To study the incidence of tetanus during the last 50 years in Sengerema, Tanzania. DESIGN: Analysing the annual reports in the only district hospital, focusing on the number of admissions and mortality for tetanus and malaria. SETTING: Sengerema Hospital, Sengerema district, Tanzania. SUBJECT: Number of admissions and mortality in Sengerema Hospital due to tetanus. INTERVENTIONS: In the seventies and eighties a vaccination campaign was started end organised in order to cover the whole district and to provide immunity for tetanus. MAIN OUTCOME MEASURES: From 1962 to 2012, we analysed the incidence and fatality rate of tetanus. RESULT: One hundred and fifteen admissions in the sixties, increasing to 183 in the seventies, dropping to 30 in the nineties. For the last ten years 18 patients with tetanus were seen in the only district hospital. Then last year no admissions for tetanus were registered. The number of deaths due to tetanus decreased simultaneously, during the last decade a single fatality case was reported. CONCLUSION: During the last decades, we have witnessed the disappearing of tetanus in Sengerema Hospital. The incidence of tetanus can be reduced significantly or eliminated by an effective immunisation programme, even in rural Tanzania. PMID- 26862658 TI - COMMUNITY PERCEPTIONS OF SCHISTOSOMIASIS TRANSMISSION, PREVALENCE AND CONTROL IN RELATION TO AQUATIC HABITATS IN THE LAKE VICTORIA BASIN OF KENYA. AB - BACKGROUND: Intestinal schistosomiasis caused by Schistosoma mansoni and urinary schistosomiasis caused by Schistosoma haematobium are widely distributed parasites in several localities of the Lake Victoria basin of Kenya, the former being more prevalent. In Kenya, transmission of the intestinal form of bilharzia (S. mansoni) tends to be closely confined to narrow zones along the shores of large bodies of water such as Lake Victoria where it is endemic and the intermediate host is found. The prevalence of S. mansoni along the Kenyan Lake Victoria basin ranges between 40% and 80%. OBJECTIVE: To assess the community's knowledge and perceptions of schistosomiasis prevalence, transmission and control in relation to aquatic habitats in the Lake Victoria basin of Kenya. DESIGN: Community-based cross-sectional study. SETTING: The Kenyan Lake Victoria basin. SUBJECTS: Two hundred and forty three individuals (both women and men residing in the beaches and surrounding areas) were interviewed about their knowledge and perceptions regarding schistosomiasis. RESULTS: The community regarded schistosomiasis as a naturalistic disease not caused by supernatural forces but by an agent of contamination in water. Knowledge on schistosomiasis transmission and control was low, with 42% of the respondents having no idea on how schistosomiasis is contracted, while 22% and 18% of the respondents mentioned contact with contaminated water and drinking / eating dirty water / food, respectively. Most respondents were familiar with the snails' habitats, but had poor knowledge on aquatic plants harbouring snails, as 57% of the respondents did not know about aquatic plants being associated with schistosomiasis snails. Only 3% of the respondents associated snails with schistosomiasis transmission. Sixty percent (60%) of the respondents mentioned use of tablets and injections as means of treating schistosomiasis, while 38% had no idea how it is treated and 2% mentioned use of local herbs and services of medicine men. CONCLUSION: Majority of Kenyan Lake Victoria basin inhabitants had little awareness about schistosomiasis despite high prevalence of the disease in the region. There is need to adapt prevention and control strategies to the people's livelihoods. There is also need to target the less advantaged members of the community such as women, uneducated and subsistence farmers for intense health education strategies aimed at increasing participation in the control of schistosomiasis. Study to elicit divergence between biomedical and local understandings of schistosomiasis/bilharzia is suggested. PMID- 26862659 TI - KNOWLEDGE, ATTITUDE AND USE OF PAIN RELIEF IN LABOUR AMONG WOMEN ATTENDING ANTE NATAL CLINIC AT SHALOM COMMUNITY HOSPITAL, ATHI RIVER. AB - OBJECTIVE: To find out the knowledge, attitude and practice of pain relief methods during labour among mothers attending antenatal clinics at Shalom Community Hospital, Athi River, Kenya. DESIGN: Cross Sectional study. SETTING: Shalom Community Hospital, Athi River, Kenya. SUBJECTS: Two hundred and seven participants attending antenatal clinics at the facility were recruited. RESULTS: The median age of the participants was 28 years and a median parity of one. Most of the study participants, 89.4%, were not aware of any pain relief method during labour. Among the 10.6% patients that were of a pain relief method, 54% had gotten the knowledge from the doctors. All the patients had experienced pain in labour with 72% rating the pain as severe pain. Only 37% of the patients were offered a pain relief method and the intramuscular injectable was offered to all. Majority (88%) of those offered a form of pain relief rated the pain relief method as ineffective. A majority of the women 93% would use a pain relief method in the next labour with epidural method being the most preferred method. CONCLUSION: The level of knowledge of pain relief methods among mothers islow. There is need to integrate information on pain relief options in labour as part of antenatal services offered routinely. Epidural analgesia services should be enhanced. PMID- 26862660 TI - Breastmilk Output in a Disadvantaged Community with High HIV Prevalence as Determined by the Deuterium Oxide Dose-to-Mother Technique. AB - INTRODUCTION: World Health Organization breastfeeding guidelines for HIV-infected mothers are exclusive breastfeeding for 6 months and then continued breastfeeding for 12 months, provided the mother is receiving antiretroviral prophylaxis. Many African women perceive that breastmilk alone is not sufficient for their infant's nutritional requirements for the first 6 months of life, and mixed feeding is a common practice. METHODOLOGY: A stable isotope technique was used to determine breastmilk output volumes and maternal body composition objectively at five different time points in the first year of the infant's life. RESULTS: Breastmilk output volumes were high for HIV-infected mothers: 831 +/- 185 g/day at 6 weeks; 899 +/- 188 g/day at 3 months; 871 +/- 293 g/day at 6 months; 679 +/- 281 g/day at 9 months; and 755 +/- 287 g/day at 12 months. These high output volumes had no negative impact on the mother's fat-free mass. The breastmilk output volumes for HIV-uninfected mothers were not significantly different to the outputs for HIV infected mothers at any of the time points (p > 0.05): 948 +/- 223 g/day at 6 weeks; 925 +/- 227 g/day at 3 months; 902 +/- 286 g/day at 6 months; 746 +/- 263 g/day at 9 months; and 713 +/- 264 g/day at 12 months. CONCLUSION: This study using objective methodology shows that breastmilk outputs of HIV-infected mothers were relatively high (and within published reference ranges), and mothers are able to provide sufficient breastmilk for their infants without compromising their own fat-free mass. PMID- 26862661 TI - Hospice-Where Peace and Turmoil Coexist. AB - It is often said that a hospice is much more than just a place providing supportive care for the terminally ill. This narrative describes Neha, a young mother who found her solace in the hospice and spent her last days there by choice. It reinforces the fact that the hospice is truly a philosophy of care where powerful and contrasting emotions do coexist. PMID- 26862662 TI - Curing HIV: Moving Forward Faster. AB - There is enormous enthusiasm in the scientific community for finding a cure for HIV. Although much remains to be discovered regarding the mechanisms of viral persistence and how it may be disrupted, some assumptions regarding the goals of a cure, applicability to target populations, and what is required of the assays we employ, may lead to missed opportunities and discoveries and hamper the discovery of a product that will safely cure tens of millions of HIV-infected people around the world. The field will benefit from an awareness and critical interrogation of assumptions that may be implicit in their scientific pursuits. PMID- 26862663 TI - Physical activity and prolonged sedentary behavior in US working adults. AB - Using nationally representative data (N = 6,431) from the 2007-2010 National Health and Nutrition Examination Survey, we estimated the prevalence of self reported adherence to guidelines-recommended physical activity level and prolonged sedentary behavior among US working adults 20 years of age and above by occupation. Sex and age were used for adjustment by direct standardization to the year 2000 Census population. Participants in "computer, mathematical" (47.77%) and "business, financial operations" (54.95%) occupations had the lowest prevalence of self-reported adherence to guidelines-recommended physical activity level; participants in "computer, mathematical" (72.19%) and "legal" (62.70%) occupations had the highest prevalence of prolonged sedentary behavior in all occupations. Public physical activity campaigns and workplace wellness programs should take into account the differences in physical activity and sedentary behavior patterns across occupation groups. PMID- 26862664 TI - Development of new PCR-based markers specific for chromosome arms of rye (Secale cereale L.). AB - PCR-based rye (Secale cereale L.) chromosome-specific markers can contribute to the effective utilization of elite genes of rye in wheat (Triticum aestivum L.) breeding programs. In the present study, 578 new PCR-based rye-specific markers have been developed by using specific length amplified fragment sequencing (SLAF seq) technology, and 76 markers displayed different polymorphism among rye Kustro, Imperial, and King II. A total of 427 and 387 markers were, respectively, located on individual chromosomes and chromosome arms of Kustro by using a set of wheat-rye monosomic addition lines and 13 monotelosomic addition lines, which were derived from T. aestivum L. 'Mianyang11' * S. cereale L. 'Kustro'. In addition, two sets of wheat-rye disomic addition lines, which were derived from T. aestivum L. var. Chinese Spring * S. cereale L. var. Imperial and T. aestivum L. 'Holdfast' * S. cereale L. var. King II, were used to test the chromosomal specificity of the 427 markers. The chromosomal locations of 281 markers were consistent among the three sets of wheat-rye addition lines. The markers developed in this study can be used to identify a given segment of rye chromosomes in wheat background and accelerate the utilization of elite genes on rye chromosomes in wheat breeding programs. PMID- 26862666 TI - Donor-Dependent Kinetics of Interfacial Proton-Coupled Electron Transfer. AB - The effect of the proton donor on the kinetics of interfacial concerted proton electron transfer (CPET) to polycrystalline Au was probed indirectly by studying the rate of hydrogen evolution from trialkylammonium donors with different steric profiles, but the same pKa. Detailed kinetic studies point to a mechanism for HER catalysis that involves rate-limiting CPET from the proton donor to the electrode surface, allowing this catalytic reaction to serve as a proxy for the rate of interfacial CPET. In acetonitrile electrolyte, triethylammonium (TEAH(+)) displays up to 20-fold faster CPET kinetics than diisopropylethylammonium (DIPEAH(+)) at all measured potentials. In aqueous electrolyte, this steric constraint is largely lifted, suggesting a key role for water in mediating interfacial CPET. In acetonitrile, TEAH(+) also displays a much larger transfer coefficient (beta = 0.7) than DIPEAH(+) (beta = 0.4), and TEAH(+) displays a potential-dependent H/D kinetic isotope effect that is not observed for DIPEAH(+). These results demonstrate that proton donor structure strongly impacts the free energy landscape for CPET to extended solid surfaces and highlight the crucial role of the proton donor in the kinetics of electrocatalytic energy conversion reactions. PMID- 26862667 TI - Does early post-operative intraperitoneal chemotherapy (EPIC) for patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) make a difference? AB - INTRODUCTION: Peritoneal carcinomatosis (PC) is increasingly being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), with or without early post-operative intraperitoneal chemotherapy (EPIC). We compared the morbidities, overall survival (OS) and disease free survival (DFS) between two groups of patients who underwent CRS and HIPEC alone and with EPIC at our institution. METHODS: A retrospective review of 111 patients with PC who were treated with CRS + HIPEC or CRS + HIPEC + EPIC in a single institution between January 2008 and April 2014 was performed. EPIC with 5 fluorouracil or paclitaxel was utilised, depending on the primary tumour. RESULTS: Patients who received EPIC had a higher proportion of grade III and above post- operative complications (58% versus 25%; p = 0.048) and a longer duration of hospitalisation (16 days versus 13 days; p = 0.019) than patients without EPIC. There were no significant OS and DFS differences between the EPIC and no EPIC groups (log-rank p = 0.231 and p = 0.144, respectively). CONCLUSION: The use of EPIC after CRS + HIPEC for PC potentially results in increased morbidity and longer hospitalisation, and is unlikely to affect survival outcomes. Based on our experience, EPIC is not recommended after CRS and HIPEC. PMID- 26862668 TI - Activation of transcription factors in human bronchial epithelial cells exposed to aqueous extracts of mainstream cigarette smoke in vitro. AB - This study aimed to identify the most sensitive transcription factor activated by cigarette smoke extract (CSE) and to explore cigarette smoke components that have high biological activities in a cell-base assay. Previously, we found evidence that implicated 10 different transcription factors as having a high biological activity to CSE in vitro, based on the results of a comprehensive gene expression profile. For this study, luciferase reporter assays for each transcription factor were developed in two types of human bronchial epithelial cells: NCI-H292 and BEAS-2B cells. The results demonstrated that the nuclear factor erythroid 2 related factor 2 (NRF2)/anti-oxidant response element (ARE) pathway was the most sensitive in response to CSE. Consistently, hemo oxygenase-1 (HO-1), a downstream target gene of NRF2, was effectively up-regulated in BEAS-2B cells exposed to CSE. Moreover, among 1395 cigarette smoke components, naphthoquinones including 9,10-phenaotrenquinone, quinones, benzenediols and alpha, beta-unsaturated carbonyls, were identified as major smoke components that contribute to activating the NRF2/ARE pathway, as indicated by the ARE-reporter assay in BEAS 2B cells. Taken together, NRF2 appears to be a key molecule in the CSE-induced cellular response, and the employed methodology is helpful for the analysis of molecular and cellular effects by CSE. PMID- 26862670 TI - Mechanisms of Nanoglass Ultrastability. AB - The origin of the astonishing properties of recently discovered ultrastable nanoglasses is presently not well understood. Nanoglasses appear to exhibit density variations not common in bulk glasses and differ significantly in thermal, magnetic, biocompatible, and mechanic properties from the bulk materials of the same composition. Here, we investigate a generic model system that permits modeling of both the physical vapor deposition process (PVD) of the nanoparticles and their consolidation into a nanoglass. We performed molecular dynamics simulations to investigate the PVD process generating nanometer-sized noncrystalline clusters and the formation of the PVD-nanoglass when these nanoclusters are consolidated. In agreement with the experiments, we find that the resulting PVD-nanoglass consists of two structural components: noncrystalline nanometer-sized cores and interfacial regions that are formed during the consolidation process. The interfacial regions were found to have an atomic structure and an internal energy that differ from the structure and internal energy of the corresponding melt-quenched glass. The resulting material represents a noncrystalline state that differs from a bulk glass with the same chemical composition and a glass obtained from nanoparticles derived from the bulk glass. PMID- 26862665 TI - Effect of N-Terminal Extension of Cardiac Troponin I on the Ca(2+) Regulation of ATP Binding and ADP Dissociation of Myosin II in Native Cardiac Myofibrils. AB - Cardiac troponin I (cTnI) has a unique N-terminal extension that plays a role in modifying the calcium regulation of cardiac muscle contraction. Restrictive cleavage of the N-terminal extension of cTnI occurs under stress conditions as a physiological adaptation. Recent studies have shown that in comparison with controls, transgenic mouse cardiac myofibrils containing cTnI lacking the N terminal extension (cTnI-ND) had a lower sensitivity to calcium activation of ATPase, resulting in enhanced ventricular relaxation and cardiac function. To investigate which step(s) of the ATPase cycle is regulated by the N-terminal extension of cTnI, here we studied the calcium dependence of cardiac myosin II ATPase kinetics in isolated cardiac myofibrils. ATP binding and ADP dissociation rates were measured by using stopped-flow spectrofluorimetry with mant-dATP and mant-dADP, respectively. We found that the second-order mant-dATP binding rate of cTnI-ND mouse cardiac myofibrils was 3-fold faster than that of wild-type myofibrils at low Ca(2+) concentrations. The ADP dissociation rate of cTnI-ND myofibrils was positively dependent on calcium concentration, while the wild-type controls were not significantly affected. These data from experiments using native cardiac myofibrils under physiological conditions indicate that modification of the N-terminal extension of cTnI plays a role in the calcium regulation of the kinetics of actomyosin ATPase. PMID- 26862669 TI - Evaluation of the capability of low-impact development practices for the removal of heavy metal from urban stormwater runoff. AB - Low-impact development (LID) and green infrastructure (GI) have recently become well-known methods to capture, collect, retain, and remove pollutants in stormwater runoff. The research was conducted to assess the efficiency of LID/GI systems applied in removing the particulate and dissolved heavy metals (Zn, Pb, Cu, Ni, Cr, Cd, and Fe) from urban stormwater runoff. A total of 82 storm events were monitored over a four-year period (2010-2014) on six LID/GI systems including infiltration trenches, tree box filter, rain garden, and hybrid constructed wetlands employed for the management of road, parking lot, and roof runoff. It was observed that the heavy metal concentration increased proportionally with the total suspended solids concentration. Among the heavy metal constituents, Fe appeared to be highly particulate-bound and was the easiest to remove followed by Zn and Pb; while metals such as Cr, Ni, Cu, and Cd were mostly dissolved and more difficult to remove. The mass fraction ratios of metal constituents at the effluent were increased relative to the influent. All the systems performed well in the removal of particulate-bound metals and were more efficient for larger storms greater than 15 mm wherein more particulate bound metals were generated compared to smaller storms less than 5 mm that produced more dissolved metals. The efficiency of the systems in removing the particulate-bound metals was restricted during high average/peak flows; that is, high-intensity storms events and when heavy metals have low concentration levels. PMID- 26862671 TI - Genomic Meningococcal Load in the Nasopharynx of Children with Meningococcal Disease. AB - This study demonstrates the feasibility of using quantitative real time PCR to measure genomic bacterial load in the nasopharynx of children with invasive meningococcal disease and shows that these loads are exceptionally high (median 6.6 * 10(5) (range 1.2 * 10(5)-1.1 * 10(8)) genome copies of Neisseria meningitidis per swab). PMID- 26862672 TI - Prolonged Shedding of Human Parechovirus in Feces of Young Children after Symptomatic Infection. AB - After symptomatic human parechovirus (HPeV) infection in infants, the duration of (mostly asymptomatic) shedding in feces was 2-24 weeks (median 58 days). HPeV cycle threshold value could neither differentiate between symptomatic disease and asymptomatic shedding nor between severe and mild disease as high cycle threshold values (indicating low viral loads) were observed in HPeV3-infected children with severe disease. PMID- 26862674 TI - Impact of the Increased Recommended Dosage of Isoniazid on Pyridoxine Levels in Children and Adolescents. AB - Isoniazid exposure causes dose-dependent pyridoxine deficiency. Recently, the recommended dosage of isoniazid in children was increased from 5 (4-6) to 10 (10 15) mg/kg/day. We aimed to analyze longitudinally pyridoxine levels in a cohort of previously healthy children and adolescents treated with isoniazid. Mild symptom-free pyridoxine deficiency was observed in 4/75 (5.6%) and 3/40 (7.5%) at baseline and at 3-month follow-up, respectively. Classical age-related risk factors identified patients at risk of pyridoxine deficiency. Our preliminary results support current recommendations regarding pyridoxine supplementation in healthy children. PMID- 26862673 TI - Cytomegalovirus Enterocolitis in Immunocompetent Young Children: A Report of Two Cases and Review of the Literature. AB - Cytomegalovirus (CMV) causes significant morbidity and mortality in congenitally infected children and immunocompromised hosts. Among healthy individuals, CMV is generally thought to cause mild, self-limited illness. CMV enterocolitis, in particular, is rarely considered among immunocompetent children presenting with diarrhea. We describe 2 cases of invasive CMV colitis in immunocompetent infants presenting with diarrhea and review the literature to date on this topic. Although invasive CMV enterocolitis has been sporadically reported among immunocompetent children, it remains an underrecognized cause of infectious diarrhea in this population and indications for antiviral therapy are lacking. We propose that CMV should be included in the differential diagnosis of intractable diarrhea in immunocompetent children. PMID- 26862675 TI - Enterovirus Infections of the Central Nervous System in Children: An Update. PMID- 26862676 TI - Therapeutic Drug Monitoring for Anti-infective Agents in Pediatrics: The Way Forward. PMID- 26862677 TI - Effects of Propylene Carbonate Content in CsPF6-Containing Electrolytes on the Enhanced Performances of Graphite Electrode for Lithium-Ion Batteries. AB - The effects of propylene carbonate (PC) content in CsPF6-containing electrolytes on the performances of graphite electrode in lithium half cells and in graphite?LiNi0.80Co0.15Al0.05O2 (NCA) full cells are investigated. It is found that the performance of graphite electrode is significantly affected by PC content in the CsPF6-containing electrolytes. An optimal PC content of 20% by weight in the solvent mixtures is identified. The enhanced electrochemical performance of graphite electrode can be attributed to the synergistic effects of the PC solvent and the Cs(+) additive. The synergistic effects of Cs(+) additive and appropriate amount of PC enable the formation of a robust, ultrathin, and compact solid electrolyte interphase (SEI) layer on the surface of graphite electrode, which is only permeable for desolvated Li(+) ions and allows fast Li(+) ion transport through it. Therefore, this SEI layer effectively suppresses the PC cointercalation and largely alleviates the Li dendrite formation on graphite electrode during lithiation even at relatively high current densities. The presence of low-melting-point PC solvent improves the sustainable operation of graphite?NCA full cells under a wide temperature range. The fundamental findings also shed light on the importance of manipulating/maintaining the electrode/electrolyte interphasial stability in various energy-storage devices. PMID- 26862678 TI - The Impact of Continuous Subcutaneous Insulin Infusion Therapy on Efficacy and Safety in a Cohort of Type 1 Diabetes Patients: A 3-Year Prospective Study. AB - BACKGROUND: Several studies have found improved glycemic control with continuous subcutaneous insulin infusion compared with multiple daily insulin injections for patients with type 1 diabetes, albeit for a relatively short-period of follow-up. This prospective study presents for the first time the optimization of glycemic control with insulin pumps in a cohort of Greek patients with type 1 diabetes for a 3-year follow-up period during the socioeconomic crisis in Greece. MATERIALS AND METHODS: Ninety-four patients, previously on intensified basal-bolus insulin therapy with poor glycemic control, were initially recruited. Glycosylated hemoglobin (HbA1c), hypoglycemic and diabetic ketoacidosis episodes, pump-related side effects, lipidemic profile, 24-h urine albumin excretion, body mass index, blood pressure, and total daily insulin requirements (bolus and basal) were recorded during the 3-year follow-up. Statistical analysis was initially conducted for the entire study population and after body mass index and gender stratification. RESULTS: Seventy-nine patients completed the study. A statistically significant decrease of HbA1c level (P < 0.0001) was observed at the end of Year 1 and was retained for the following years for the whole population. Similarly, significantly fewer hypoglycemic episodes occurred during the follow-up period (P < 0.0001) compared with study entry. Insulin pump treatment was not accompanied with weight changes across all body mass index strata. CONCLUSIONS: Continuous subcutaneous insulin infusion achieved almost optimal glycemic control, reduced the number of hypoglycemic episodes without weight gain, and was well tolerated for the whole study period. Finally, this therapeutic approach was accompanied with lower daily insulin requirements. PMID- 26862679 TI - Comparative evaluation of features and techniques for identifying activity type and estimating energy cost from accelerometer data. AB - Wearable accelerometers can be used to objectively assess physical activity. However, the accuracy of this assessment depends on the underlying method used to process the time series data obtained from accelerometers. Several methods have been proposed that use this data to identify the type of physical activity and estimate its energy cost. Most of the newer methods employ some machine learning technique along with suitable features to represent the time series data. This paper experimentally compares several of these techniques and features on a large dataset of 146 subjects doing eight different physical activities wearing an accelerometer on the hip. Besides features based on statistics, distance based features and simple discrete features straight from the time series were also evaluated. On the physical activity type identification task, the results show that using more features significantly improve results. Choice of machine learning technique was also found to be important. However, on the energy cost estimation task, choice of features and machine learning technique were found to be less influential. On that task, separate energy cost estimation models trained specifically for each type of physical activity were found to be more accurate than a single model trained for all types of physical activities. PMID- 26862680 TI - Nonclassical 21-Homododecahedryl Cation Rearrangement Revisited. AB - The degenerate rearrangement in the 21-homododecahedryl cation (1) has been studied via density functional theory computations and Born-Oppenheimer Molecular Dynamics simulations. Compound 1 can be described as a highly fluxional hyperconjugated carbocation. Complete scrambling of 1 can be achieved by the combination of two unveiled barrierless processes. The first one is a "rotation" of one of the six-membered rings via a 0.8 kcal.mol(-1) barrier, and the second one is a slower interconvertion between two hyperconjomers via an out-of-plane methine bending (DeltaG(?) = 4.0 kcal.mol(-1)). PMID- 26862681 TI - Exchange Coupling Inversion in a High-Spin Organic Triradical Molecule. AB - The magnetic properties of a nanoscale system are inextricably linked to its local environment. In adatoms on surfaces and inorganic layered structures, the exchange interactions result from the relative lattice positions, layer thicknesses, and other environmental parameters. Here, we report on a sample dependent sign inversion of the magnetic exchange coupling between the three unpaired spins of an organic triradical molecule embedded in a three-terminal device. This ferro-to-antiferromagnetic transition is due to structural distortions and results in a high-to-low spin ground-state change in a molecule traditionally considered to be a robust high-spin quartet. Moreover, the flexibility of the molecule yields an in situ electric tunability of the exchange coupling via the gate electrode. These findings open a route to the controlled reversal of the magnetic states in organic molecule-based nanodevices by mechanical means, electrical gating, or chemical tailoring. PMID- 26862683 TI - The Application of Aptamers for Immunohistochemistry. AB - Immunohistochemistry has helped to make surgical pathology the "gold" standard for tumor diagnosis. However, given the numerous problems associated with the use of antibodies for the staining of cellular markers in paraffin-embedded tissues, there is a requirement for novel agents that have the advantages of antibodies, but with few of the disadvantages. Aptamers, which are chemical antibodies, are highly specific and sensitive, like their protein counterparts, but display few of the disadvantages. These molecules represent a unique reagent that has the potential to revolutionize the field of histopathological diagnostics. In this study, we present a review of some of the aptamers that have been validated for use in diagnoses and suggest some of the advantages to using these molecules in the future. PMID- 26862684 TI - Self-Assembly of Structures with Addressable Complexity. AB - The self-assembly of structures with "addressable complexity", where every component is distinct and is programmed to occupy a specific location within a target structure, is a promising route to engineering materials with precisely defined morphologies. Because systems with many components are inherently complicated, one might assume that the chances of successful self-assembly are extraordinarily small. Yet recent advances suggest otherwise: addressable structures with hundreds of distinct building blocks have been designed and assembled with nanometer precision. Despite this remarkable success, it is often challenging to optimize a self-assembly reaction to ensure that the intended structure is kinetically accessible. In this Perspective, we focus on the prediction of kinetic pathways for self-assembly and implications for the design of robust experimental protocols. The development of general principles to predict these pathways will enable the engineering of complex materials using a much wider range of building blocks than is currently possible. PMID- 26862682 TI - A Hospital-Based Advance Care Planning Intervention for Patients with Heart Failure: A Feasibility Study. AB - BACKGROUND: Early discussions about advance care planning (ACP) have been associated with improved patient and caregiver outcomes for patients with serious illness. Many patients with heart failure (HF) may benefit from more timely ACP, in part due to the unpredictable trajectory of the disease. OBJECTIVES: The purpose of this study was to evaluate the feasibility of implementing a multiple component hospital-based intervention on completion of ACP forms among HF patients. METHODS: A brief hospital-based ACP intervention was led by a nonclinician health educator that included (1) an educational video about shared decision making and (2) a protocol to engage HF providers in patients' ACP decision making after the hospitalization. We surveyed patients regarding attitudes toward the ACP intervention and studied completion rates of advance directives (ADs) or physician orders for life sustaining treatment (POLST) forms six months following discharge. RESULTS: The educational video component of this intervention was considered helpful by 92% of participants, and 70% said they were more likely to talk with their physician about their end-of-life preferences after watching the video and interacting with the health educator. Of 37 participants, 49% had evidence of completion of an AD or POLST in their medical records six months after the index hospitalization compared to 32% before the intervention. The number of patients having a signed scanned POLST form increased from 10 (27%) before the intervention to 16 (43%) six months after the intervention (p = 0.03). CONCLUSIONS: A hospital-based ACP intervention using nonclinician health educators is feasible to implement and has the potential to facilitate the ACP process. PMID- 26862685 TI - RN-BSN Students' Perceptions of the Differences in Practice of the ADN- and BSN Prepared RN. AB - This study explored RN-BSN students' perceptions of practice differences between nurses prepared with an ADN and BSN. Five themes were identified in 20 students' discussion posts: "a nurse is a nurse" at the bedside, beyond the bedside, BSN wanted, digging deeper, and appraisal. Results illustrate the need for educators to assist nurses in translating the differentiated educational competencies to the practice role of the bedside RN. PMID- 26862686 TI - Conducting a Multisite Education Research Project: Strategies to Overcome the Barriers to Achieve the Benefits. AB - Multisite education research projects have many benefits as well as perceived barriers. In this article, we share our experiences with a multisite education research project and the barriers we overcame to reap the benefits. The outcome of our research resulted in increased rigor, role-modeling professional collaboration, and promotion of future multisite education studies. The strategies presented in this article will help alleviate perceived barriers and ameliorate the process of conducting multisite education research studies. PMID- 26862687 TI - Palliative Care Education in Nurse Practitioner Programs: A Survey of Academic Deans. AB - The need for clinicians trained in palliative care will increase as more Americans live with life-limiting illness. Although multiple studies have described the nature of palliative care education in prelicensure programs, there have been no similar studies of nurse practitioner programs. We surveyed 101 nurse practitioner programs. Most programs provide little instruction in palliative care; education is often limited to a few hours of lecture. One-third of programs offer no instruction. Although palliative care is an important component of advanced practice nursing practice, programs may not be providing adequate education. PMID- 26862688 TI - Use of Standardized Patients to Enhance Simulation of Medication Administration. PMID- 26862689 TI - Thermodynamic Study on the Protonation Reactions of Glyphosate in Aqueous Solution: Potentiometry, Calorimetry and NMR spectroscopy. AB - Glyphosate [N-(phosphonomethyl)glycine] has been described as the ideal herbicide because of its unique properties. There is some conflicting information concerning the structures and conformations involved in the protonation process of glyphosate. Protonation may influence the chemical and physical properties of glyphosate, modifying its structure and the chemical processes in which it is involved. To better understand the species in solution associated with changes in pH, thermodynamic study (potentiometry, calorimetry and NMR spectroscopy) about the protonation pathway of glyphosate is performed. Experimental results confirmed that the order of successive protonation sites of totally deprotonated glyphosate is phosphonate oxygen, amino nitrogen, and finally carboxylate oxygen. This trend is in agreement with the most recent theoretical work in the literature on the subject (J. Phys. Chem. A 2015, 119, 5241-5249). The result is important because it confirms that the protonated site of glyphosate in pH range 7-8, is not on the amino but on the phosphonate group instead. This corrected information can improve the understanding of the glyphosate chemical and biochemical action. PMID- 26862692 TI - Bone regeneration in rat femoral defects after osteotomy with surgical ultrasound. AB - To evaluate bone healing after osteotomy by surgical drill (D) and piezoelectric ultrasound (U), Wistar rats were submitted to femoral osteotomy and submitted to histological analysis. After 60 h, slight (83.3%) and moderate (3.4%) inflammatory areas were frequent in the U defects whereas D group presented moderate (33.3%) and severe (16.6%) inflammatory infiltrate (P<0.001). There was few intramedullary hemorrhaging in U (80%) than D group (100%, P<0.05). On the 7th day, inflammatory areas was less frequent in U (30%) than D osteotomies (93.4%) (P<0.005) and D osteotomies presented larger areas of ossification (median: 47%, quartile: 37-64%) than U group (30%, 18.5-38%; P<0.005). After 30 days, ossification was larger in the U defects (65.9+/-10.1%) than D group (57+/ 14.5%, P<0.05). There was complete bone remodeling in both groups after 60 days. Piezoelectric ultrasound evokes less postoperative inflammatory response, but delay initial bone ossification. PMID- 26862693 TI - Comparative CBCT evaluation of the efficacy of Nd:YAG laser and K3 rotary system in non-surgical root canal retreatment. AB - BACKGROUND: The aim of the present study was to compare the efficacy of Nd:YAG laser and K3 rotary system in the non-surgical root canal retreatment. METHODS: Sixty-one rooted human teeth were divided into two groups of 30 after root canal therapy. In groups 1 and 2 root canal retreatments were carried out using K3 rotary system and Nd:YAG laser, respectively. CBCT images were used to evaluate canal transportation and root canal debridement at coronal, middle and apical canal cross-sections. In addition, the time necessary for canal debridement and the temperature on the external root surface were calculated. Mann-Whitney U test was used for statistical analysis of data with SPSS 17 after means +/- SD were calculated. Shapiro-Wilk test was used to evaluate normal distribution of data. Statistical significance was defined at P<0.05. RESULTS: The mean time necessary for the debridement of root canals in the laser group was significantly shorter than that in the K3 group (P=0.001). However, there were no significant differences in external root surface temperatures between the two groups (P=0.17). The coronal third of the canals was cleaner in the laser group significantly (p=0.01). Less canal transportation was seen in the laser group compared to the K3 group, significantly (P=0.04). CONCLUSIONS: Nd:YAG is superior to K3 rotary system in the non-surgical root canal retreatment because it is faster and results in less canal transportation in the middle and apical thirds of the canals. PMID- 26862694 TI - Retrospective review of 78 rehabilitated head and neck postoncological patients: a new classification method. AB - BACKGROUND: Numerous studies have been published about the prosthetic rehabilitation of the postoncological maxillo-facial patient, but the guidelines that emerge lack a correlation between the anatomical classification of the treated site, which generally is preparatory upon surgery, and the type of prosthetic rehabilitation appropriate to the new anatomical and functional condition. With this correlation, it would be possible to obtain a multidisciplinary and predictable therapeutic process, able to identify from the beginning the best type of prosthetic rehabilitation. METHODS: The authors analyzed a sample of 78 patients treated in the Maxillofacial Surgery Unit of "Sapienza" University of Rome for a tumor of the head and neck area, and at a later stage prosthetically rehabilitated in the years from 2010 to 2013 in the Prosthetic Rehabilitation Unit of the same University because of the consequences of the ablative surgery. After having analyzed data concerning the treatment of the maxillofacial tumor, Authors classified the kind of prosthetic rehabilitation. Removable prosthesis was chosen in 18 cases, while implant (or teeth)-supported rehabilitation was performed in 60 cases. RESULTS: Authors correlated the kind of surgical reconstruction to the prosthetic rehabilitation performed. In the maxilla removable prosthesis was chosen in 8 cases, while implant supported rehabilitation was performed in 18 cases. In the mandible 10 cases were rehabilitated through a removable prosthesis and 42 through a teeth or implant supported prosthesis. CONCLUSIONS: It is evident the need to perform a careful evaluation of the patient, in order to identify the best possible prosthetic rehabilitation. PMID- 26862695 TI - Prognostic value of lymph node ratio for locoregional failure in patients with advanced head and neck cancers. AB - BACKGROUND: In the current study, the utility of lymph node ratio (LNR) was evaluated as an alternative method for predicting locoregional failure in patients with advanced head and neck cancer. METHODS: Fifty-six patients with oral and (pharyngo)laryngeal squamous cell carcinoma were included. Among those, 48 were males and 8 females, with a mean age of 58 years. The primary tumor was located in the oral cavity in 16 cases, involved the larynx in 17 cases and the hypopharynx in 23 cases. All the tumors were staged T4. We carried out 112 neck dissections. All the lymph nodes harvested from the neck dissection were carefully examined, with LNR calculated as the ratio of positive lymph nodes to total lymph nodes removed. All the patients received adjuvant (chemo)radiotherapy. RESULTS: Receiver operating characteristic curve analysis showed LNR was significantly associated with locoregional failure. LNR >0.09 (as the cutoff point) could predict locoregional failure after surgery for oral and (pharyngo)laryngeal cancers with a sensibility of 93% and specificity of 100%. CONCLUSIONS: After surgery, pathologic evaluation of the neck using LNR was found to reliably predict the risk of locoregional recurrence in patients with advanced head and neck cancers. PMID- 26862696 TI - Reliability and efficacy of palifermin in prevention and management of oral mucositis in patients with acute lymphoblastic leukemia: a randomized, double blind controlled clinical trial. AB - BACKGROUND: Myeloablative and hematopoietic stem cells transplantation therapy (HSCT) often acts as side-effect to oral mucositis (OM) with no effective treatment. This randomized-controlled trial analyzed the efficacy of palifermin, administered as a dose during HSCT therapy, as primary prophylaxis on pediatric patients with acute lymphoblastic leukemia (ALL). METHODS: In this study forty six patients (9-15 years) with B-cell acute lymphoblastic leukemia (B-ALL) were analyzed. The patients underwent allogenic HSCT conditioned by myeloablative regimen. Subsequently to randomization, patients in the palifermin group were assigned to receive palifermin, 60 mg/kg, intravenously as a single dose 3 days before and after transplant conditioning regimen cycle. The patients in the Control group received only a placebo treatment. Maximum severity of OM, incidence and duration of ulcerative OM, incidence and duration of severe OM limitations were evaluated. RESULTS: A statistically significant reduction in the incidence of OM up to grade 3 in the palifermin group compared to the control group was discovered. There was also a reduction, confirmed at 60 days, in the degree of severity of mucositis in the palifermin group, with an average of 1.54 grade in the palifermin group, and of 2.16 in the Control group and in the use of opioid analgesics. CONCLUSIONS: This study indicates that a single dose of palifermin used as primary prophylaxis during HSTC therapy can prevent severe OM in pediatric patients with ALL and used as secondary prophylaxis can prevent the recurrence of severe OM in high-risk patients with previous mucosal injury and improves the quality of life in pediatric patients with ALL. PMID- 26862697 TI - Multiple mandibular fractures. Treatment outlines. AB - Multiple mandibular comminuted fractures usually occur in high energy traumas. The authors describe the management and treatment of multiple mandibular fractures in a young patient after a suicide attempt. PMID- 26862698 TI - The Fire Challenge: A Case Report and Analysis of Self-Inflicted Flame Injury Posted on Social Media. AB - With the advent of social media platforms such as Facebook and YouTube, online dissemination of exhibitionist videos has gained popularity. One recent disturbing trend is the "fire challenge" wherein a participant douses his or herself in a household accelerant such as isopropyl alcohol or acetone, sets him or herself ablaze, and attempts to extinguish the flames before serious burns are incurred. As expected, participants in the "fire challenge" often accidentally suffer serious burns. A 17-year-old white male was recently treated at our burn center after participating in the "fire challenge." He suffered 15% TBSA full and partial thickness burns requiring split thickness skin grafting to his abdomen. He reported lighting himself on fire because he had seen this stunt performed on the internet. A search for "fire challenge" and similar terms was conducted on YouTube (www.youtube.com). Gender and ethnicity of each participant were documented. Burn size, burn depth, and age of video participant were estimated by two attending burn surgeons evaluating YouTube videos. Results were reported with descriptive statistics. The search yielded thousands of hits, mostly home videos, compilations of stunts, and commentaries. After omitting duplicate and irrelevant videos, 50 videos were selected for the study. Of these, 13 videos included postburn footage demonstrating burn wounds of various location, size, and severity. Of these burns, the median TBSA burned was 4 +/- 2.7% with a maximum size of 10%. Superficial and partial thickness burns were sustained on the torso (10/13, 77%), face (4/13, 31%), and extremities (2/13, 15%). Full thickness burns were seen in 2/13 videos. Some burn wounds were obscured by dressings. Of the 50 videos reviewed, 45/50 participants (90%) were male and 32/50 (64%) were African American with 29/50 participants (58%) estimated to be under age 20. The "fire challenge" is a popular social media phenomenon, but it can result in severe injury as seen with the patient at our institution. The lure of a challenge and potential for a shocking video to "go viral" might entice people to mimic this risky behavior. This study shows a disturbing trend, but undoubtedly only reflects a small portion of actual participants. A disproportionate number of videos featured young African American males, making this a target population for education and prevention efforts. Our patient's TBSA exceeded the maximum found on YouTube, suggesting that less severe burns may be posted online while larger burns are not, diminishing perceived risk and encouraging this behavior. PMID- 26862699 TI - A New Look at the Blade Implant. PMID- 26862700 TI - Functional Cloning Using a Xenopus Oocyte Expression System. AB - Identification of genes responsible for embryonic induction poses a number of challenges; to name a few, secreted molecules of interest may be low in abundance, may not be secreted but tethered to the signaling cell(s), or may require the presence of binding partners or upstream regulatory molecules. Thus in a search for gene products capable of eliciting an early lens-inductive response in competent ectoderm, we utilized an expression cloning system that would allow identification of paracrine or juxtacrine factors as well as transcriptional or other regulatory proteins. Pools of mRNA were injected into Xenopus oocytes, and responding tissue placed directly on the oocytes and co cultured. Following functional cloning of ldb1 from a neural plate stage cDNA library based on its ability to elicit the expression of the early lens placode marker foxe3 in lens-competent animal cap ectoderm, we characterized the mRNA expression pattern, and assayed developmental progression following overexpression or knockdown of ldb1. This system is suitable in a very wide variety of contexts where identification of an inducer or its upstream regulatory molecules is sought using a functional response in competent tissue. PMID- 26862701 TI - Epigenetic Classification of Human Mesenchymal Stromal Cells. AB - Standardization of mesenchymal stromal cells (MSCs) is hampered by the lack of a precise definition for these cell preparations; for example, there are no molecular markers to discern MSCs and fibroblasts. In this study, we followed the hypothesis that specific DNA methylation (DNAm) patterns can assist classification of MSCs. We utilized 190 DNAm profiles to address the impact of tissue of origin, donor age, replicative senescence, and serum supplements on the epigenetic makeup. Based on this, we elaborated a simple epigenetic signature based on two CpG sites to classify MSCs and fibroblasts, referred to as the Epi MSC-Score. Another two-CpG signature can distinguish between MSCs from bone marrow and adipose tissue, referred to as the Epi-Tissue-Score. These assays were validated by site-specific pyrosequencing analysis in 34 primary cell preparations. Furthermore, even individual subclones of MSCs were correctly classified by our epigenetic signatures. In summary, we propose an alternative concept to use DNAm patterns for molecular definition of cell preparations, and our epigenetic scores facilitate robust and cost-effective quality control of MSC cultures. PMID- 26862702 TI - Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Valpha24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells. AB - Valpha24 invariant natural killer T (iNKT) cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer. Conversely, reduced iNKT cell numbers and function have been observed in many patients with cancer. To recover these numbers, we reprogrammed human iNKT cells to pluripotency and then re-differentiated them into regenerated iNKT cells in vitro through an IL-7/IL-15-based optimized cytokine combination. The re differentiated iNKT cells showed proliferation and IFN-gamma production in response to alpha-galactosylceramide, induced dendritic cell maturation and downstream activation of both cytotoxic T lymphocytes and NK cells, and exhibited NKG2D- and DNAM-1-mediated NK cell-like cytotoxicity against cancer cell lines. The immunological features of re-differentiated iNKT cells and their unlimited availability from induced pluripotent stem cells offer a potentially effective immunotherapy against cancer. PMID- 26862704 TI - Ex vivo Live Imaging of Lung Metastasis and Their Microenvironment. AB - Metastasis is a major cause for cancer-related morbidity and mortality. Metastasis is a multistep process and due to its complexity, the exact cellular and molecular processes that govern metastatic dissemination and growth are still elusive. Live imaging allows visualization of the dynamic and spatial interactions of cells and their microenvironment. Solid tumors commonly metastasize to the lungs. However, the anatomical location of the lungs poses a challenge to intravital imaging. This protocol provides a relatively simple and quick method for ex vivo live imaging of the dynamic interactions between tumor cells and their surrounding stroma within lung metastasis. Using this method, the motility of cancer cells as well as interactions between cancer cells and stromal cells in their microenvironment can be visualized in real time for several hours. By using transgenic fluorescent reporter mice, a fluorescent cell line, injectable fluorescently labeled molecules and/or antibodies, multiple components of the lung microenvironment can be visualized, such as blood vessels and immune cells. To image the different cell types, a spinning disk confocal microscope that allows long-term continuous imaging with rapid, four-color image acquisition has been used. Time-lapse movies compiled from images collected over multiple positions and focal planes show interactions between live metastatic and immune cells for at least 4 hr. This technique can be further used to test chemotherapy or targeted therapy. Moreover, this method could be adapted for the study of other lung-related pathologies that may affect the lung microenvironment. PMID- 26862706 TI - HeRBi: Helmholtz Repository of Bioparts. PMID- 26862703 TI - What Is Trophoblast? A Combination of Criteria Define Human First-Trimester Trophoblast. AB - Controversy surrounds reports describing the derivation of human trophoblast cells from placentas and embryonic stem cells (ESC), partly due to the difficulty in identifying markers that define cells as belonging to the trophoblast lineage. We have selected criteria that are characteristic of primary first-trimester trophoblast: a set of protein markers, HLA class I profile, methylation of ELF5, and expression of microRNAs (miRNAs) from the chromosome 19 miRNA cluster (C19MC). We tested these criteria on cells previously reported to show some phenotypic characteristics of trophoblast: bone morphogenetic protein (BMP) treated human ESC and 2102Ep, an embryonal carcinoma cell line. Both cell types only show some, but not all, of the four trophoblast criteria. Thus, BMP-treated human ESC have not fully differentiated to trophoblast. Our study identifies a robust panel, including both protein and non-protein-coding markers that, in combination, can be used to reliably define cells as characteristic of early trophoblast. PMID- 26862705 TI - Repeatability and Reproducibility of Spectral-Domain Optical Coherence Tomography Measurements of Retinal Thickness in Rats. AB - PURPOSE: To evaluate the in vivo repeatability and reproducibility of spectral domain optical coherence tomography (SD-OCT) measurements of total retinal thickness (TRT) and retinal nerve fiber layer (RNFL) thickness in rats. METHODS: Retinal thickness was measured using an RNFL circular scan with AutoRescan and TruTracking modes in 20 eyes of Long-Evans Tokushima Otsuka rats. Three RNFL circular scan images were acquired with a brief rest between measurements to evaluate intra-session repeatability. Three additional RNFL circular scans were acquired 1 day later to evaluate intersession repeatability. Two experienced examiners independently measured TRT using automatic alignment and RNFL thickness using manual alignment according to the same procedure to evaluate inter-examiner reproducibility 1 week later. The correlation of measurements by OCT and histology was determined. RESULTS: For TRT, the intra-session and inter-session intraclass correlation coefficient (ICC) with SD-OCT was between 0.85 and 0.93. The coefficient of variance (CV) ranged from 3.9% to 4.8%. For RNFL thickness, intra-session, and inter-session ICC with SD-OCT were between 0.61 and 0.91. The inter-examiner ICC was 0.74 for TRT and 0.70 for RNFL. The CV was 4.4% for TRT and 6.0% for RNFL. OCT and histologically determined TRT and RNFL thicknesses were significantly positively related based on Pearson's correlation coefficient (TRT, r = 0.781, p < 0.001; RNFL, r = 0.517, p = 0.019). CONCLUSIONS: TRT and RNFL thickness measurements using SD-OCT in rats had high intra-session and inter session repeatability and inter-examiner reproducibility in vivo. This method will facilitate longitudinal studies to follow disease processes over time and to evaluate therapeutic effects after experimental intervention. PMID- 26862707 TI - BMI and BMI SDS in childhood: annual increments and conditional change. AB - Background Early detection of abnormal weight gain in childhood may be important for preventive purposes. It is still debated which annual changes in BMI should warrant attention. Aim To analyse 1-year increments of Body Mass Index (BMI) and standardised BMI (BMI SDS) in childhood and explore conditional change in BMI SDS as an alternative method to evaluate 1-year changes in BMI. Subjects and methods The distributions of 1-year increments of BMI (kg/m2) and BMI SDS are summarised by percentiles. Differences according to sex, age, height, weight, initial BMI and weight status on the BMI and BMI SDS increments were assessed with multiple linear regression. Conditional change in BMI SDS was based on the correlation between annual BMI measurements converted to SDS. Results BMI increments depended significantly on sex, height, weight and initial BMI. Changes in BMI SDS depended significantly only on the initial BMI SDS. The distribution of conditional change in BMI SDS using a two-correlation model was close to normal (mean = 0.11, SD = 1.02, n = 1167), with 3.2% (2.3-4.4%) of the observations below -2 SD and 2.8% (2.0-4.0%) above +2 SD. Conclusion Conditional change in BMI SDS can be used to detect unexpected large changes in BMI SDS. Although this method requires the use of a computer, it may be clinically useful to detect aberrant weight development. PMID- 26862709 TI - Validity and Feasibility Evidence of Objective Structured Clinical Examination to Assess Competencies of Pediatric Critical Care Trainees. AB - OBJECTIVE: The purpose of this study was to provide validity and feasibility evidence for the use of an objective structured clinical examination in the assessment of pediatric critical care medicine trainees. DESIGN: This was a validation study. Validity evidence was based on Messick's framework. SETTING: A tertiary, university-affiliated academic center. SUBJECTS: Seventeen pediatric critical care medicine fellows were recruited in 2012 and 2013 academic year. INTERVENTIONS: None. All subjects completed an objective structured clinical examination assessment. MEASUREMENTS AND MAIN RESULTS: Seventeen trainees were assessed. Simulation scenarios were developed for content validity by pediatric critical care medicine and education experts using CanMEDS competencies. Scenarios were piloted before the study. Each scenario was evaluated by two interprofessional raters. Inter-rater agreement, measured using intraclass correlations, was 0.91 (SE = 0.09) across stations. Generalizability theory was used to evaluate internal structure and reliability. Reliability was moderate (G coefficient = 0.67, Phi-coefficient = 0.52). The greatest source of variability was from participant by station variance (40.6%). Pearson correlation coefficients were used to evaluate the relationship of objective structured clinical examination with each traditional assessment instruments: multisource feedback, in-training evaluation report, short-answer questions, and Multidisciplinary Critical Care Knowledge Assessment Program. Performance on the objective structured clinical examination correlated with performance on the Multidisciplinary Critical Care Knowledge Assessment Program (r = 0.52; p = 0.032) and multisource feedback (r = 0.59; p = 0.017), but not with the overall performance on the in-training evaluation report (r = 0.37; p = 0.143) or short answer questions (r = 0.08; p = 0.767). Consequences were not assessed. CONCLUSION: Validity and feasibility evidence in this study indicate that the use of the objective structured clinical examination scores can be a valid way to assess CanMEDS competencies required for independent practice in pediatric critical care medicine. PMID- 26862710 TI - The growth of ZnO on stainless steel foils by MOCVD and its application in light emitting devices. AB - Direct fabrication of semiconductor light emitting devices on metal foils is beneficial, because it brings flexibility and good heat sink in the devices. In this work, we have grown ZnO on the commercially available stainless steel foils by metal-organic chemical vapor deposition for the first time. With the increase of growth temperature, the morphology changes from a thin film structure to closely stacked columns, and eventually to nanorods. The change in the migration ability of adatoms due to the increase of growth temperature plays an important role in the evolution of morphology. The samples with nanorod morphology exhibit relatively better crystallinity and optical quality. A PEDOT: PSS/PMMA/ZnO device was fabricated based on the grown ZnO nanorods. The metal-insulator-semiconductor type device shows an uncommon symmetric I-V curve. Under reverse bias, the device emits fairly pure UV light, which comes from the near band edge emission of ZnO. The working mechanism of the devices has been discussed, and a model mainly based on the Poole-Frenkel effect is proposed to describe the charge transportation of the devices. PMID- 26862708 TI - Use of Biotelemetry to Define Physiology-Based Deterioration Thresholds in a Murine Cecal Ligation and Puncture Model of Sepsis. AB - OBJECTIVES: Murine models of critical illness are commonly used to test new therapeutic interventions. However, these interventions are often administered at fixed time intervals after the insult, perhaps ignoring the inherent variability in magnitude and temporality of the host response. We propose to use wireless biotelemetry monitoring to define and validate criteria for acute deterioration and generate a physiology-based murine cecal ligation and puncture model that is more similar to the conduct of human trials of sepsis. DESIGN: Laboratory and animal research. SETTING: University basic science laboratory. SUBJECTS: Male C57BL/6 mice. INTERVENTIONS: Mice underwent cecal ligation and puncture, and an HD-X11 wireless telemetry monitor (Data Sciences International) was implanted that enabled continuous, real-time measurement of heart rate, core temperature, and mobility. We performed a population-based analysis to determine threshold criteria that met face validity for acute physiologic deterioration. We assessed construct validity by temporally matching mice that met these acute physiologic deterioration thresholds with mice that had not yet met deterioration threshold. We analyzed matched blood samples for blood gas, inflammatory cytokine concentration, cystatin C, and alanine aminotransferase. MEASUREMENTS AND MAIN RESULTS: We observed that a 10% reduction in both heart rate and temperature sustained for greater than or equal to 10 minutes defined acute physiologic deterioration. There was significant variability in the time to reach acute deterioration threshold across mice, ranging from 339 to 529 minutes after cecal ligation and puncture. We found adequate construct validity, as mice that met criteria for acute deterioration had significantly worse shock, systemic inflammation (elevated tumor necrosis factor-alpha, p = 0.003; interleukin-6, p = 0.01; interleukin-10, p = 0.005), and acute kidney injury when compared with mice that had not yet met acute deterioration criteria. CONCLUSIONS: We defined a murine threshold for acute physiologic deterioration after cecal ligation and puncture that has adequate face and construct validity. This model may enable a more physiology-based model for evaluation of novel therapeutics in critical illness. PMID- 26862711 TI - A Binaural Cochlear Implant Sound Coding Strategy Inspired by the Contralateral Medial Olivocochlear Reflex. AB - OBJECTIVES: In natural hearing, cochlear mechanical compression is dynamically adjusted via the efferent medial olivocochlear reflex (MOCR). These adjustments probably help understanding speech in noisy environments and are not available to the users of current cochlear implants (CIs). The aims of the present study are to: (1) present a binaural CI sound processing strategy inspired by the control of cochlear compression provided by the contralateral MOCR in natural hearing; and (2) assess the benefits of the new strategy for understanding speech presented in competition with steady noise with a speech-like spectrum in various spatial configurations of the speech and noise sources. DESIGN: Pairs of CI sound processors (one per ear) were constructed to mimic or not mimic the effects of the contralateral MOCR on compression. For the nonmimicking condition (standard strategy or STD), the two processors in a pair functioned similarly to standard clinical processors (i.e., with fixed back-end compression and independently of each other). When configured to mimic the effects of the MOCR (MOC strategy), the two processors communicated with each other and the amount of back-end compression in a given frequency channel of each processor in the pair decreased/increased dynamically (so that output levels dropped/increased) with increases/decreases in the output energy from the corresponding frequency channel in the contralateral processor. Speech reception thresholds in speech-shaped noise were measured for 3 bilateral CI users and 2 single-sided deaf unilateral CI users. Thresholds were compared for the STD and MOC strategies in unilateral and bilateral listening conditions and for three spatial configurations of the speech and noise sources in simulated free-field conditions: speech and noise sources colocated in front of the listener, speech on the left ear with noise in front of the listener, and speech on the left ear with noise on the right ear. In both bilateral and unilateral listening, the electrical stimulus delivered to the test ear(s) was always calculated as if the listeners were wearing bilateral processors. RESULTS: In both unilateral and bilateral listening conditions, mean speech reception thresholds were comparable with the two strategies for colocated speech and noise sources, but were at least 2 dB lower (better) with the MOC than with the STD strategy for spatially separated speech and noise sources. In unilateral listening conditions, mean thresholds improved with increasing the spatial separation between the speech and noise sources regardless of the strategy but the improvement was significantly greater with the MOC strategy. In bilateral listening conditions, thresholds improved significantly with increasing the speech-noise spatial separation only with the MOC strategy. CONCLUSIONS: The MOC strategy (1) significantly improved the intelligibility of speech presented in competition with a spatially separated noise source, both in unilateral and bilateral listening conditions; (2) produced significant spatial release from masking in bilateral listening conditions, something that did not occur with fixed compression; and (3) enhanced spatial release from masking in unilateral listening conditions. The MOC strategy as implemented here, or a modified version of it, may be usefully applied in CIs and in hearing aids. PMID- 26862712 TI - Testing Speech Recognition in Spanish-English Bilingual Children with the Computer-Assisted Speech Perception Assessment (CASPA): Initial Report. AB - This study evaluated the English version of Computer-Assisted Speech Perception Assessment (E-CASPA) with Spanish-English bilingual children. E-CASPA has been evaluated with monolingual English speakers ages 5 years and older, but it is unknown whether a separate norm is necessary for bilingual children. Eleven Spanish-English bilingual and 12 English monolingual children (6 to 12 years old) with normal hearing participated. Responses were scored by word, phoneme, consonant, and vowel. Regardless of scores, performance across three signal-to noise ratio conditions was similar between groups, suggesting that the same norm can be used for both bilingual and monolingual children. PMID- 26862714 TI - New Eu(3+)-activated perovskite La(0.5)Na(0.5)TiO3 phosphors in glass for warm white light emitting diodes. AB - With an increasing demand for high-power warm white light emitting diodes (w LEDs), the discovery of efficient red-emitting inorganic color converters is in great demand. Herein, a novel perovskite La0.5Na0.5TiO3:Eu(3+) red-emitting phosphor with excellent thermal stability and high quantum efficiency has been successfully synthesized by a traditional solid-state reaction. Then, the developed La0.5Na0.5TiO3:Eu(3+) red phosphor and commercial YAG:Ce(3+) yellow phosphor were incorporated into an innovatively designed low-melting glass. Impressively, the destruction of La0.5Na0.5TiO3:Eu(3+) and YAG:Ce(3+) phosphor particles during glass melting was quite low. Remarkably, the fabricated w-LEDs using an InGaN-based blue chip combined with Phosphor in Glass (PiG) plates exhibited an improved chromaticity feature and superior optical performance. Through simply adjusting the content of red phosphors in the PiG, the correlated color temperature of the PiG-based w-LEDs evolved from cool white (6771 K) to warm white (4417 K) and the color rendering index increased from 73.4 to 86.4. Moreover, the PiG-based warm w-LEDs presented superior thermal stability. PMID- 26862713 TI - Electrochemical detection of peroxynitrite using hemin-PEDOT functionalized boron doped diamond microelectrode. AB - Peroxynitrite is a potent nitroxidation agent and highly reactive metabolite, clinically correlated with a rich pathophysiology. Its sensitive and selective detection is challenging due to its high reactivity and short sub-second lifetime. Boron-doped diamond (BDD) microelectrodes have attracted interest because of their outstanding electroanalytical properties that include a wide working potential window and enhanced signal-to-noise ratio. Herein, we report on the modification of a BDD microelectrode with an electro-polymerized film of hemin and polyethylenedioxythiophene (PEDOT) for the purpose of selectively quantifying peroxynitrite. The nanostructured modified polymer layer was characterized by Raman spectroscopy and scanning electron microscopy (SEM). The electrochemical response to peroxynitrite was studied by voltammetry and time based amperometry. The measured detection limit was 10 +/- 0.5 nM (S/N = 3), the sensitivity was 4.5 +/- 0.5 nA nM(-1) and the response time was 3.5 +/- 1 s. The hemin-PEDOT BDD sensors exhibited a response variability of 5% or less (RSD). The stability of the sensors after a 20-day storage in 0.1 M PB (pH 7.4) at 4 degrees C was excellent as at least 93% of the initial response to 50 nM PON was maintained. The presence of PEDOT was correlated with a sensitivity increase. PMID- 26862715 TI - Cortex-, Hippocampus-, Thalamus-, Hypothalamus-, Lateral Septal Nucleus- and Striatum-specific In Utero Electroporation in the C57BL/6 Mouse. AB - In utero electroporation is a widely used technique for fast and efficient spatiotemporal manipulation of various genes in the rodent central nervous system. Overexpression of desired genes is just as possible as shRNA mediated loss-of-function studies. Therefore it offers a wide range of applications. The feasibility to target particular cells in a distinct area further increases the range of potential applications of this very useful method. For efficiently targeting specific regions knowledge about the subtleties, such as the embryonic stage, the voltage to apply and most importantly the position of the electrodes, is indispensable. Here, we provide a detailed protocol that allows for specific and efficient in utero electroporation of several regions of the C57BL/6 mouse central nervous system. In particular it is shown how to transfect regions the develop into the retrosplenial cortex, the motor cortex, the somatosensory cortex, the piriform cortex, the cornu ammonis 1-3, the dentate gyrus, the striatum, the lateral septal nucleus, the thalamus and the hypothalamus. For this information about the appropriate embryonic stage, the appropriate voltage for the corresponding embryonic stage is provided. Most importantly an angle-map, which indicates the appropriate position of the positive pole, is depicted. This standardized protocol helps to facilitate efficient in utero electroporation, which might also lead to a reduced number of animals. PMID- 26862716 TI - Acrylic Resin Molding Based Head Fixation Technique in Rodents. AB - Head fixation is a technique of immobilizing animal's head by attaching a head post on the skull for rigid clamping. Traditional head fixation requires surgical attachment of metallic frames on the skull. The attached frames are then clamped to a stationary platform resulting in immobilization of the head. However, metallic frames for head fixation have been technically difficult to design and implement in general laboratory environment. In this study, we provide a novel head fixation method. Using a custom-made head fixation bar, head mounter is constructed during implantation surgery. After the application of acrylic resin for affixing implants such as electrodes and cannula on the skull, additional resins applied on top of that to build a mold matching to the port of the fixation bar. The molded head mounter serves as a guide rails, investigators conveniently fixate the animal's head by inserting the head mounter into the port of the fixation bar. This method could be easily applicable if implantation surgery using dental acrylics is necessary and might be useful for laboratories that cannot easily fabricate CNC machined metal head-posts. PMID- 26862717 TI - O2 activation at the Au/MgO(001) interface boundary facilitates CO oxidation. AB - Density functional theory calculations reveal that the work function of Au supported on MgO(001) is substantially reduced because of an interfacial dipole moment formed at the Au/MgO interface. Consequently, the Au/MgO interface plays an active role in the activation of O2 molecules by promoting charge transfer to the O2 2pi* orbital. The presence of F-centers in the MgO substrate can further promote the charge transfer and bonding of O2 at the interface boundary. However, O2 dissociation is kinetically hindered. The system is then able to catalyze CO oxidation at low temperature as adsorbed CO and O2 readily react to form CO2 with a low energy barrier. PMID- 26862718 TI - Isolation of Specific Genomic Regions and Identification of Associated Molecules by enChIP. AB - The identification of molecules associated with specific genomic regions of interest is required to understand the mechanisms of regulation of the functions of these regions. To enable the non-biased identification of molecules interacting with a specific genomic region of interest, we recently developed the engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) technique. Here, we describe how to use enChIP to isolate specific genomic regions and identify the associated proteins and RNAs. First, a genomic region of interest is tagged with a transcription activator-like (TAL) protein or a clustered regularly interspaced short palindromic repeats (CRISPR) complex consisting of a catalytically inactive form of Cas9 and a guide RNA. Subsequently, the chromatin is crosslinked and fragmented by sonication. The tagged locus is then immunoprecipitated and the crosslinking is reversed. Finally, the proteins or RNAs that are associated with the isolated chromatin are subjected to mass spectrometric or RNA sequencing analyses, respectively. This approach allows the successful identification of proteins and RNAs associated with a genomic region of interest. PMID- 26862719 TI - Successful Anesthesia Management for 2-Stage Surgical Procedure of a Refractory Tracheogastric Tube Fistula After Esophagectomy. AB - Tracheogastric tube fistulas are rare but fatal complications after esophagectomy. Anesthetic management for a patient with this complication is challenging because air leakage and mechanical ventilation may cause aspiration. We present a case report of the anesthetic management of a patient having 2-stage surgical repair combined with endoscopic mucosal resection for a giant carinal tracheogastric tube fistula. The first stage was separation of the gastric tube above the fistula with spontaneous breathing under local anesthesia and sedation. The second stage was complete separation and reconstruction of the digestive tract under epidural and general anesthesia with spontaneous breathing and pressure support before insertion of a decompression tube. PMID- 26862721 TI - Changes in Postpartum Insulin Requirements for Patients with Well-Controlled Type 1 Diabetes. AB - Objective To compare postpartum with preconception insulin doses in well controlled (HbA1c <= 7.4%) type 1 diabetes mellitus (T1DM) and to characterize differences in postpartum insulin dosing based on infant feeding. Study Design The primary outcome in this retrospective cohort was the change in total daily insulin (TDI) from preconception to postpartum. Insulin administration (continuous subcutaneous insulin infusion [CSII] vs. multiple daily injections [MDI]), HbA1c, body mass index (BMI), and infant feeding were abstracted. Results We identified 44 women with T1DM and HbA1c <= 7.4%. Preconception mean BMI was 24.6 +/- 3.6 kg/m(2) and median (interquartile range [IQR]) HbA1c was 6.4 (6.0 6.9)%. Of these, 73% used CSII and 27% used MDI. Additionally, 80% of patients reported exclusive breastfeeding, 7% were exclusively formula feeding, and 13% used both breast milk and formula. Median (IQR) preconception TDI was 0.64 (0.49 0.69) U/kg/day, and postpartum: 0.39 (0.30-0.50) U/kg/day. Postpartum TDI was 34% lower than preconception TDI (p = 0.02). There was no difference in the postpartum TDI in patients who were breast versus formula feeding or when comparing CSII with MDI. Conclusion There was a significant decrease in the TDI required postpartum when compared with preconception. Dosages do not seem to be impacted by administration route or breastfeeding. These findings warrant consideration when dosing postpartum insulin in patients with T1DM. PMID- 26862720 TI - DamID-seq: Genome-wide Mapping of Protein-DNA Interactions by High Throughput Sequencing of Adenine-methylated DNA Fragments. AB - The DNA adenine methyltransferase identification (DamID) assay is a powerful method to detect protein-DNA interactions both locally and genome-wide. It is an alternative approach to chromatin immunoprecipitation (ChIP). An expressed fusion protein consisting of the protein of interest and the E. coli DNA adenine methyltransferase can methylate the adenine base in GATC motifs near the sites of protein-DNA interactions. Adenine-methylated DNA fragments can then be specifically amplified and detected. The original DamID assay detects the genomic locations of methylated DNA fragments by hybridization to DNA microarrays, which is limited by the availability of microarrays and the density of predetermined probes. In this paper, we report the detailed protocol of integrating high throughput DNA sequencing into DamID (DamID-seq). The large number of short reads generated from DamID-seq enables detecting and localizing protein-DNA interactions genome-wide with high precision and sensitivity. We have used the DamID-seq assay to study genome-nuclear lamina (NL) interactions in mammalian cells, and have noticed that DamID-seq provides a high resolution and a wide dynamic range in detecting genome-NL interactions. The DamID-seq approach enables probing NL associations within gene structures and allows comparing genome-NL interaction maps with other functional genomic data, such as ChIP-seq and RNA seq. PMID- 26862722 TI - Protocol versus Nonprotocol Dosing of Vancomycin in Neonates: A Single Center Evaluation of Steady State Trough Levels. AB - Objective This study aims to assess the need for modification of the current vancomycin dosing protocol at a single institution by conducting a comparison of dosing per protocol versus off protocol and the resulting first troughs in neonates. Secondary outcomes include comparison of time to first therapeutic steady-state trough, dose at first therapeutic steady-state trough, and success of the consult-to-pharmacy service. Study Design This single center retrospective chart review analyzed patients at a level-IIIb neonatal intensive care unit who received vancomycin and had at least one appropriately drawn trough level documented from 2013 to 2014. Effectiveness of each dosing strategy was evaluated by assessing troughs. Results Approximately 30% of first vancomycin trough levels obtained are within the desired range of 15 to 20 ug/mL and patients achieve therapeutic steady-state trough levels after 3.6 days, regardless of the initial dosing strategy. The current protocol reflects the therapeutic steady state dosing only 22% of the time. The vancomycin consult-to-pharmacy service improves the achievement of goal trough ranges. Conclusion An assessment of doses that achieved a goal vancomycin trough of 15 to 20 ug/mL revealed that a dose of 12.5 mg/kg at the same intervals and age ranges specified in the current protocol would enable the achievement of this higher goal trough. PMID- 26862723 TI - Pulmonary Vein Stenosis in Neonates with Severe Bronchopulmonary Dysplasia. AB - Objectives Pulmonary vein stenosis (PVS) is a rare, often lethal anomaly associated with poor outcomes. Given the association between bronchopulmonary dysplasia (BPD) and cardiovascular complications, we tested the hypotheses that (1) a subgroup of neonates with severe BPD develop PVS (BPD-PVS) and have worse outcomes than do neonates with severe BPD alone (BPD); (2) among a cohort of neonates with severe BPD-associated pulmonary hypertension (BPD-PH), PVS is an additional risk factor for adverse outcomes and mortality. Study Design We performed a retrospective review of neonates with severe BPD, based on the Eunice Kennedy Shriver National Institute of Child Health and Development (NICHD) criteria, at our institution between June 1, 2009, and June 30, 2013. PVS was determined based on serial review of echocardiograms performed during their hospitalization. Neonates with congenital heart disease or chromosomal anomalies were excluded. Results Of 213 patients with severe BPD, 10 (4.7%) were found to have PVS (BPD-PVS). Neonates with BPD-PVS had lower birth weight (634 +/- 178 vs. 767 +/- 165 g; p < 0.01) and were more likely to be intrauterine growth restricted (80 vs. 11%; p < 0.01) than neonates with BPD alone. Time on mechanical ventilation and length of hospitalization were longer in the BPD-PVS group than BPD group. Survival was lower in the BPD-PVS group than BPD group (5/10 [50%] vs. 196/203 [97%]; log-rank test p < 0.01). Among a subgroup of neonates with BPD-PH, survival was lower among infants with PVS than those without PVS (5/9 [56%] vs. 26/30 [86%]; log-rank test p = 0.01). Conclusions Compared with neonates with severe BPD alone, those with acquired PVS are at increased risk for worse outcomes, including higher mortality. Evidence-based recommendations regarding screening protocols and surveillance are needed in this high-risk subgroup of BPD neonates. PMID- 26862724 TI - Nonreassuring Fetal Status in the Second Stage of Labor: Fetal Monitoring Features and Association with Neonatal Outcomes. AB - Objective To examine features of electronic fetal monitoring that prompt a diagnosis of nonreassuring fetal status (NRFS) and their association with acidemia. Study Design We identified all operative (cesarean or operative vaginal) deliveries from a retrospective cohort study of term singletons delivered in the second stage. The primary exposure was indication for delivery, NRFS versus other. We compared fetal monitoring features in the 30 minutes prior to delivery. In those delivered for NRFS, we assessed features associated with acidemia (pH < 7.2). Logistic regression adjusted for confounders. Results Of 5,388 patients, 770 (14%) were delivered operatively. NRFS (77%) was associated with acidemia (adjusted odds ratio 3.7, 95% confidence interval 2.1-6.5). Total deceleration area, repetitive late decelerations, and marked variability were associated with NRFS. However, only number of prolonged decelerations and total deceleration area were associated with acidemia in the NRFS group. Conclusion The majority of deliveries for NRFS and the features that prompt that diagnosis are not associated with acidemia. PMID- 26862725 TI - Idiopathic Polyhydramnios: Severity and Perinatal Morbidity. AB - Objective To estimate the association between the severity of idiopathic polyhydramnios and adverse outcomes. Study Design Retrospective cohort study of deliveries at one hospital from 2000 to 2012 with an amniotic fluid index (AFI) measurement >=24 + 0 weeks' gestation. Pregnancies complicated by diabetes, multiples, or fetal anomalies were excluded. Exposure was the degree of polyhydramnios: normal (AFI 5-24 cm), mild (>= 24-30 cm), and moderate-severe (> 30 cm). Primary outcomes were perinatal mortality, neonatal intensive care unit (NICU) admission, and postpartum hemorrhage. Results There were 10,536 pregnancies: 10,188 with a normal AFI, 274 mild (78.74%), and 74 moderate-severe polyhydramnios (21.26%). Adverse outcomes were increased with idiopathic polyhydramnios: NICU admission (adjusted odds ratio [AOR] 3.71, 95% confidence interval [CI] 2.77-4.99), postpartum hemorrhage (AOR 15.81, 95% CI 7.82-31.96), macrosomia (AOR 3.41, 95% CI 2.61-4.47), low 5-minute Apgar score (AOR 2.60, 95% CI 1.57-4.30), and cesarean (AOR 2.16, 95% CI 1.74-2.69). There were increasing odds of macrosomia (mild: AOR 3.19, 95% CI 2.36-4.32; moderate-severe: AOR 4.44, 95% CI 2.53-7.79) and low 5-minute Apgar score (mild: AOR 2.24, 95% CI 1.23-4.08; moderate-severe: AOR 3.93, 95% CI 1.62-9.55) with increasing severity of polyhydramnios. Conclusion Idiopathic polyhydramnios is independently associated with increased risks of morbidity. There appears to be a dose-response relationship for neonatal macrosomia and low 5-minute Apgar score risks. PMID- 26862726 TI - "The More the Better" Paradox of Antenatal Ultrasound Examinations in Low-Risk Pregnancy. AB - Objective To investigate whether different antenatal care models could account for differences in operative delivery rates and adverse neonatal outcomes among low-risk pregnant women, and to identify independent variables associated with delivery modes and adverse neonatal outcomes. Study design Retrospective cohort from a single center of singleton, term, live births between January 2012 and June 2014. Rates of cesarean deliveries, operative vaginal deliveries, and neonatal morbidities were analyzed among women followed by private obstetrician gynecologists versus national health system providers (certified nurse midwifes supervised by obstetrician-gynecologists), and adjusted for potential confounders. Results Among the 2,831 women in our cohort, obstetric and neonatal outcomes were independent of obstetric providers. After we controlled for confounders, private patients having more than four antenatal ultrasound examinations were more likely to undergo cesarean delivery than public patients with four or fewer sonographic assessments (five to eight prenatal scans: relative risk ratio, 3.3; 95% confidence interval [CI] 1.4-8; nine or more prenatal scans: relative risk ratio, 4.1; 95% CI 1.2-14). Conclusions Multiple prenatal ultrasound examinations in low-risk obstetric populations appear to be an independent and potentially modifiable risk factor for cesarean deliveries. PMID- 26862727 TI - The hormone response element mimic sequence of GAS5 lncRNA is sufficient to induce apoptosis in breast cancer cells. AB - Growth arrest-specific 5 (GAS5) lncRNA promotes apoptosis, and its expression is down-regulated in breast cancer. GAS5 lncRNA is a decoy of glucocorticoid/related receptors; a stem-loop sequence constitutes the GAS5 hormone response element mimic (HREM), which is essential for the regulation of breast cancer cell apoptosis. This preclinical study aimed to determine if the GAS5 HREM sequence alone promotes the apoptosis of breast cancer cells. Nucleofection of hormone sensitive and -insensitive breast cancer cell lines with a GAS5 HREM DNA oligonucleotide increased both basal and ultraviolet-C-induced apoptosis, and decreased culture viability and clonogenic growth, similar to GAS5 lncRNA. The HREM oligonucleotide demonstrated similar sequence specificity to the native HREM for its functional activity and had no effect on endogenous GAS5 lncRNA levels. Certain chemically modified HREM oligonucleotides, notably DNA and RNA phosphorothioates, retained pro-apoptotic. activity. Crucially the HREM oligonucleotide could overcome apoptosis resistance secondary to deficient endogenous GAS5 lncRNA levels. Thus, the GAS5 lncRNA HREM sequence alone is sufficient to induce apoptosis in breast cancer cells, including triple-negative breast cancer cells. These findings further suggest that emerging knowledge of structure/function relationships in the field of lncRNA biology can be exploited for the development of entirely novel, oligonucleotide mimic-based, cancer therapies. PMID- 26862728 TI - Screening the yeast genome for energetic metabolism pathways involved in a phenotypic response to the anti-cancer agent 3-bromopyruvate. AB - In this study the detailed characteristic of the anti-cancer agent 3 bromopyruvate (3-BP) activity in the yeast Saccharomyces cerevisiae model is described, with the emphasis on its influence on energetic metabolism of the cell. It shows that 3-BP toxicity in yeast is strain-dependent and influenced by the glucose-repression system. Its toxic effect is mainly due to the rapid depletion of intracellular ATP. Moreover, lack of the Whi2p phosphatase results in strongly increased sensitivity of yeast cells to 3-BP, possibly due to the non functional system of mitophagy of damaged mitochondria through the Ras-cAMP-PKA pathway. Single deletions of genes encoding glycolytic enzymes, the TCA cycle enzymes and mitochondrial carriers result in multiple effects after 3-BP treatment. However, it can be concluded that activity of the pentose phosphate pathway is necessary to prevent the toxicity of 3-BP, probably due to the fact that large amounts of NADPH are produced by this pathway, ensuring the reducing force needed for glutathione reduction, crucial to cope with the oxidative stress. Moreover, single deletions of genes encoding the TCA cycle enzymes and mitochondrial carriers generally cause sensitivity to 3-BP, while totally inactive mitochondrial respiration in the rho0 mutant resulted in increased resistance to 3-BP. PMID- 26862730 TI - Ras-activated RSK1 phosphorylates EBP50 to regulate its nuclear localization and promote cell proliferation. AB - Differential subcellular localization of EBP50 leads to its controversial role in cancer biology either as a tumor suppressor when it resides at the membrane periphery, or a tumor facilitator at the nucleus. However, the mechanism behind nuclear localization of EBP50 remains unclear. A RNA interference screening identified the downstream effector of the Ras-ERK cascade, RSK1, as the molecule unique for nuclear transport of EBP50. RSK1 binds to EBP50 and phosphorylates it at a conserved threonine residue at position 156 (T156) under the regulation of growth factor. Mutagenesis experiments confirmed the significance of T156 residue in nuclear localization of EBP50, cellular proliferation, and oncogenic transformation. Our study sheds light on a possible therapeutic strategy targeting at this aberrant nuclear expression of EBP50 without affecting the normal physiological function of EBP50 at other subcellular localization. PMID- 26862729 TI - Inhibitors of histone deacetylase 1 reverse the immune evasion phenotype to enhance T-cell mediated lysis of prostate and breast carcinoma cells. AB - The clinical promise of cancer immunotherapy relies on the premise that the immune system can recognize and eliminate tumor cells identified as non-self. However, tumors can evade host immune surveillance through multiple mechanisms, including epigenetic silencing of genes involved in antigen processing and immune recognition. Hence, there is an unmet clinical need to develop effective therapeutic strategies that can restore tumor immune recognition when combined with immunotherapy, such as immune checkpoint blockade and therapeutic cancer vaccines. We sought to examine the potential of clinically relevant exposure of prostate and breast human carcinoma cells to histone deacetylase (HDAC) inhibitors to reverse tumor immune escape to T-cell mediated lysis. Here we demonstrate that prostate (LNCAP) and breast (MDA-MB-231) carcinoma cells are more sensitive to T-cell mediated lysis in vitro after clinically relevant exposure to epigenetic therapy with either the pan-HDAC inhibitor vorinostat or the class I HDAC inhibitor entinostat. This pattern of immunogenic modulation was observed against a broad range of tumor-associated antigens, such as CEA, MUC1, PSA, and brachyury, and associated with augmented expression of multiple proteins involved in antigen processing and tumor immune recognition. Genetic and pharmacological inhibition studies identified HDAC1 as a key determinant in the reversal of carcinoma immune escape. Further, our findings suggest that the observed reversal of tumor immune evasion is driven by a response to cellular stress through activation of the unfolded protein response. This offers the rationale for combining HDAC inhibitors with immunotherapy, including therapeutic cancer vaccines. PMID- 26862731 TI - Chromothripsis-like chromosomal rearrangements induced by ionizing radiation using proton microbeam irradiation system. AB - Chromothripsis is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event, rather than an accumulation of a series of subsequent and random alterations. Chromothripsis occurs commonly in various human cancers and is thought to be associated with increased malignancy and carcinogenesis. However, the causes and consequences of chromothripsis remain unclear. Therefore, to identify the mechanism underlying the generation of chromothripsis, we investigated whether chromothripsis could be artificially induced by ionizing radiation. We first elicited DNA double-strand breaks in an oral squamous cell carcinoma cell line HOC313-P and its highly metastatic subline HOC313-LM, using Single Particle Irradiation system to Cell (SPICE), a focused vertical microbeam system designed to irradiate a spot within the nuclei of adhesive cells, and then established irradiated monoclonal sublines from them, respectively. SNP array analysis detected a number of chromosomal copy number alterations (CNAs) in these sublines, and one HOC313-LM-derived monoclonal subline irradiated with 200 protons by the microbeam displayed multiple CNAs involved locally in chromosome 7. Multi-color FISH showed a complex translocation of chromosome 7 involving chromosomes 11 and 12. Furthermore, whole genome sequencing analysis revealed multiple de novo complex chromosomal rearrangements localized in chromosomes 2, 5, 7, and 20, resembling chromothripsis. These findings suggested that localized ionizing irradiation within the nucleus may induce chromothripsis-like complex chromosomal alterations via local DNA damage in the nucleus. PMID- 26862732 TI - Aberrant gene methylation in non-neoplastic mucosa as a predictive marker of ulcerative colitis-associated CRC. AB - BACKGROUND PROMOTER: hypermethylation plays a major role in cancer through transcriptional silencing of critical genes. The aim of our study is to evaluate the methylation status of these genes in the colonic mucosa without dysplasia or adenocarcinoma at the different steps of sporadic and UC-related carcinogenesis and to investigate the possible role of genomic methylation as a marker of CRC. RESULTS: The expression of Dnmts 1 and 3A was significantly increased in UC related carcinogenesis compared to non inflammatory colorectal carcinogenesis. In non-neoplastic colonic mucosa, the number of methylated genes resulted significantly higher in patients with CRC and in those with UC-related CRC compared to the HC and UC patients and patients with dysplastic lesion of the colon. The number of methylated genes in non-neoplastic colonic mucosa predicted the presence of CRC with good accuracy either in non inflammatory and inflammatory related CRC. METHODS: Colonic mucosal samples were collected from healthy subjects (HC) (n = 30) and from patients with ulcerative colitis (UC) (n = 29), UC and dysplasia (n = 14), UC and cancer (n = 10), dysplastic adenoma (n = 14), and colon adenocarcinoma (n = 10). DNA methyltransferases-1, -3a, -3b, mRNA expression were quantified by real time qRT-PCR. The methylation status of CDH13, APC, MLH1, MGMT1 and RUNX3 gene promoters was assessed by methylation-specific PCR. CONCLUSIONS: Methylation status of APC, CDH13, MGMT, MLH1 and RUNX3 in the non-neoplastic mucosa may be used as a marker of CRC: these preliminary results could allow for the adjustment of a patient's surveillance interval and to select UC patients who should undergo intensive surveillance. PMID- 26862733 TI - The mechanism of acquired resistance to irreversible EGFR tyrosine kinase inhibitor-afatinib in lung adenocarcinoma patients. AB - INTRODUCTION: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are associated with favorable response in EGFR mutant lung cancer. Acquired resistance to reversible EGFR TKIs remains a significant barrier, and acquired EGFR T790M-mutation is the major mechanism. Second-generation irreversible EGFR TKI, afatinib, had also been approved for treating EGFR mutant lung cancer patients, but the mechanism of acquired resistance to afatinib has not been well studied. RESULTS: Forty-two patients had tissue specimens taken after acquiring resistance to afatinib. The sensitizing EGFR mutation were all consistent between pre- and post-afatinib tissues. Twenty patients (47.6%) had acquired T790M mutation. T790M rate was not different between first-generation EGFR TKI-naive patients (50%) and first-generation EGFR TKI-treated patients (46.4%) (p = 0.827). No clinical characteristics or EGFR mutation types were associated with the development of acquired T790M. No other second-site EGFR mutations were detected. There were no small cell or squamous cell lung cancer transformation. Other genetic mutations were not identified in PIK3CA, BRAF, HER2, KRAS, NRAS, MEK1, AKT2, LKB1 and JAK2. METHODS: Afatinib-prescription record of our department of pharmacy from January 2007 and December 2014 was retrieved. We investigated patients with tissue specimens available after acquiring resistance to afatinib. Enrolled patients should have partial response or durable stable disease of treatment response to afatinib. Various mechanisms of acquired resistance to first-generation EGFR TKIs were evaluated. Histology and cytology were reviewed. EGFR, PIK3CA, BRAF, HER2, KRAS, NRAS, MEK1, AKT2, LKB1 and JAK2 genetic alterations were evaluated by sequencing. Statistical analysis was performed using Chi-square test and Kaplan-Meier method. CONCLUSIONS: T790M was detected in half of the lung adenocarcinoma after acquiring resistance to afatinib. T790M is still the major acquired resistance mechanism. First-generation EGFR TKI exposure did not influence the prevalence of T790M in lung cancer acquired resistance to afatinib. PMID- 26862734 TI - Bisleuconothine A, a bisindole alkaloid, inhibits colorectal cancer cell in vitro and in vivo targeting Wnt signaling. AB - Wnt signaling pathway is aberrantly activated in a variety of cancers, especially in colorectal cancer and small molecule antagonists of Wnt/beta-catenin signaling are attractive candidates for developing effective therapeutics. In the present study, we identified Bisleuconothine A, a bisindole alkaloid with an eburnane aspidosperma type skeleton, as a novel and selective Wnt signaling inhibitor by using a cell-based luciferase assay system. Our study found that Bisleuconothine A down-regulated the endogenous Wnt target gene expression through promoting phosphorylation of beta-catenin and the subsequent inhibition of its nuclear translocation in HCT116 and SW480 colorectal cancer cells. In vitro, Bisleuconothine A inhibited cell proliferation through induction of apoptosis by increasing the cleavage of caspases in HCT116 and SW480 colorectal cancer cells. Moreover, in vivo, Bisleuconothine A dramatically suppressed tumor growth in HCT116 Xenograft. And further analysis showed that Bisleuconothine A suppressed the Wnt target gene expression in HCT116 Xenograft, which was associated with up regulation of beta-catenin phosphorylation and subsequent Wnt signaling inhibition. Taken together, our study indicated that bisindole alkaloids could be included as a new chemotype of small-molecule Wnt signaling inhibitors, and have great potential to be further developed for anti-tumor agents. PMID- 26862735 TI - Selective brain penetrable Nurr1 transactivator for treating Parkinson's disease. AB - Parkinson's disease (PD) is one of the most common movement disorders, and currently there is no effective treatment that can slow disease progression. Preserving and enhancing DA neuron survival is increasingly regarded as the most promising therapeutic strategy for treating PD. IRX4204 is a second generation retinoid X receptor (RXR) agonist that has no cross reactivity with retinoic acid receptors, farnesoid X receptor, liver X receptors or peroxisome proliferator activated receptor PPARgamma. We found that IRX4204 promotes the survival and maintenance of nigral dopaminergic (DA) neurons in a dose-dependent manner in primary mesencephalic cultures. Brain bioavailability studies demonstrate that IRX4204 can cross the blood brain barrier and reach the brain at nM concentration. Oral administration of IRX4204 can activate nuclear receptor Nurr1 downstream signaling in the substantia nigra (SN) andattenuate neurochemical and motor deficits in a rat model of PD. Our study suggests that IRX4204 represents a novel, potent and selective pharmacological means to activate cellular RXR-Nurr1 signaling and promote SN DA neuron survival in PD prevention and/or treatment. PMID- 26862737 TI - Perlecan/HSPG2 and matrilysin/MMP-7 as indices of tissue invasion: tissue localization and circulating perlecan fragments in a cohort of 288 radical prostatectomy patients. AB - Prostate cancer (PCa) cells use matrix metalloproteinases (MMPs) to degrade tissue during invasion. Perlecan/HSPG2 is degraded at basement membranes, in reactive stroma and in bone marrow during metastasis. We previously showed MMP-7 efficiently degrades perlecan. We now analyzed PCa tissue and serum from 288 prostatectomy patients of various Gleason grades to decipher the relationship between perlecan and MMP-7 in invasive PCa. In 157 prostatectomy specimens examined by tissue microarray, perlecan levels were 18% higher than their normal counterparts. In Gleason grade 4 tissues, MMP-7 and perlecan immunostaining levels were highly correlated with each other (average correlation coefficient of 0.52) in PCa tissue, regardless of grade. Serial sections showed intense, but non overlapping, immunostaining for MMP-7 and perlecan at adjacent borders, reflecting the protease-substrate relationship. Using a capture assay, analysis of 288 PCa sera collected at prostatectomy showed elevated levels of perlecan fragments, with most derived from domain IV. Perlecan fragments in PCa sera were associated with overall MMP-7 staining levels in PCa tissues. Domain IV perlecan fragments were present in stage IV, but absent in normal, sera, suggesting perlecan degradation during metastasis. Together, perlecan fragments in sera and MMP-7 in tissues of PCa patients are measures of invasive PCa. PMID- 26862741 TI - Computational study on the unbinding pathways of B-RAF inhibitors and its implication for the difference of residence time: insight from random acceleration and steered molecular dynamics simulations. AB - B-RAF kinase is a clinically validated target implicated in melanoma and advanced renal cell carcinoma (RCC). PLX4720 and TAK-632 are promising inhibitors against B-RAF with different dissociation rate constants (k(off)), but the specific mechanism that determines the difference of their dissociation rates remains unclear. In order to understand the kinetically different behaviors of these two inhibitors, their unbinding pathways were explored by random acceleration and steered molecular dynamics simulations. The random acceleration molecular dynamics (RAMD) simulations show that PLX4720 dissociates along the ATP-channel, while TAK-632 dissociates along either the ATP-channel or the allosteric-channel. The steered molecular dynamics (SMD) simulations reveal that TAK-632 is more favorable to escape from the binding pocket through the ATP-channel rather than the allosteric-channel. The PMF calculations suggest that TAK-632 presents longer residence time, which is in qualitative agreement with the experimental k(off)(k(off) = 3.3 * 10(-2) s(-1) and DeltaG(off) = -82.17 +/- 0.29 kcal mol(-1) for PLX4720; k(off) = 1.9 * 10(-5) s(-1) and DeltaG(off) = -39.73 +/- 0.79 kcal mol(-1) for PLX4720). Furthermore, the binding free decomposition by MM/GBSA illustrates that the residues K36, E54, V57, L58, L120, I125, H127, G146 and D147 located around the allosteric binding pocket play important roles in determining the longer residence time of TAK-632 by forming stronger hydrogen bond and hydrophobic interactions. Our simulations provide valuable information to design selective B-RAF inhibitors with long residence time in the future. PMID- 26862736 TI - Synergistic antitumor activity of histone deacetylase inhibitors and anti-ErbB3 antibody in NSCLC primary cultures via modulation of ErbB receptors expression. AB - ErbB3, a member of the ErbB family receptors, has a key role in the development and progression of several cancers, including non-small cell lung cancer (NSCLC), and in the establishment of resistance to therapies, leading to the development of anti-ErbB3 therapies.In this study we demonstrated, in a set of malignant pleural effusion-derived cultures of NSCLC, the synergistic antitumor effect of a histone deacetylase inhibitor (HDACi), such as vorinostat or valproic acid (VPA), in combination with the anti-ErbB3 monoclonal antibody (MoAb) A3. Synergistic interaction was observed in 2D and in 3D cultures conditions, both in fully epithelial cells expressing all ErbB receptors, and in cells that had undergone epithelial to mesenchymal transition and expressed low levels of ErbB3. We provided evidences suggesting that differential modulation of ErbB receptors by vorinostat or VPA, also at low doses corresponding to plasma levels easily reached in treated patients, is responsible for the observed synergism. In details, we showed in epithelial cells that both vorinostat and VPA induced time- and dose-dependent down-regulation of all three ErbB receptors and of downstream signaling. On the contrary, in A3-resistant mesenchymal cells, we observed time- and dose-dependent increase of mRNA and protein levels as well as surface expression of ErbB3, paralleled by down-regulation of EGFR and ErbB2. Our results suggest that the combination of a HDACi plus an anti-ErbB3 MoAb represents a viable strategy that warrants further evaluation for the treatment of NSCLC patients. PMID- 26862738 TI - Identification of drugs that restore primary cilium expression in cancer cells. AB - The development of cancer is often accompanied by a loss of the primary cilium, a microtubule-based cellular protrusion that functions as a cellular antenna and that puts a break on cell proliferation. Hence, restoration of the primary cilium in cancer cells may represent a novel promising approach to attenuate tumor growth. Using a high content analysis-based approach we screened a library of clinically evaluated compounds and marketed drugs for their ability to restore primary cilium expression in pancreatic ductal cancer cells. A diverse set of 118 compounds stimulating cilium expression was identified. These included glucocorticoids, fibrates and other nuclear receptor modulators, neurotransmitter regulators, ion channel modulators, tyrosine kinase inhibitors, DNA gyrase/topoisomerase inhibitors, antibacterial compounds, protein inhibitors, microtubule modulators, and COX inhibitors. Certain compounds also dramatically affected the length of the cilium. For a selection of compounds (Clofibrate, Gefitinib, Sirolimus, Imexon and Dexamethasone) their ability to restore ciliogenesis was confirmed in a panel of human cancer cell line models representing different cancer types (pancreas, lung, kidney, breast). Most compounds attenuated cell proliferation, at least in part through induction of the primary cilium, as demonstrated by cilium removal using chloral hydrate. These findings reveal that several commonly used drugs restore ciliogenesis in cancer cells, and warrant further investigation of their antineoplastic properties. PMID- 26862743 TI - Maternal Attachment Representation and Neurophysiological Processing during the Perception of Infants' Emotional Expressions. AB - The perception of infant emotions is an integral part of sensitive caregiving within the mother-child relationship, a maternal ability which develops in mothers during their own attachment history. In this study we address the association between maternal attachment representation and brain activity underlying the perception of infant emotions. Event related potentials (ERPs) of 32 primiparous mothers were assessed during a three stimulus oddball task presenting negative, positive and neutral emotion expressions of infants as target, deviant or standard stimuli. Attachment representation was assessed with the Adult Attachment Interview during pregnancy. Securely attached mothers recognized emotions of infants more accurately than insecurely attached mothers. ERPs yielded amplified N170 amplitudes for insecure mothers when focusing on negative infant emotions. Secure mothers showed enlarged P3 amplitudes to target emotion expressions of infants compared to insecure mothers, especially within conditions with frequent negative infant emotions. In these conditions, P3 latencies were prolonged in insecure mothers. In summary, maternal attachment representation was found associated with brain activity during the perception of infant emotions. This further clarifies psychological mechanisms contributing to maternal sensitivity. PMID- 26862742 TI - Protection of Human Pancreatic Islets from Lipotoxicity by Modulation of the Translocon. AB - Type 2 diabetes is characterized by peripheral insulin resistance and pancreatic beta cell dysfunction. Elevated free fatty acids (FFAs) may impair beta cell function and mass (lipotoxicity). Altered calcium homeostasis may be involved in defective insulin release. The endoplasmic reticulum (ER) is the major intracellular calcium store. Lipotoxicity induces ER stress and in parallel an ER calcium depletion through unknown ER calcium leak channels. The main purposes of this study is first to identify one of these channels and secondly, to check the opportunity to restore beta cells function (i.e., insulin secretion) after pharmacological inhibition of ER calcium store depletion. We investigated the functionality of translocon, an ER calcium leak channel and its involvement on FFAs-induced alterations in MIN6B1 cells and in human pancreatic islets. We evidenced that translocon acts as a functional ER calcium leak channel in human beta cells using anisomycin and puromycin (antibiotics), respectively blocker and opener of this channel. Puromycin induced a significant ER calcium release, inhibited by anisomycin pretreatment. Palmitate treatment was used as FFA model to induce a mild lipotoxic effect: ER calcium content was reduced, ER stress but not apoptosis were induced and glucose induced insulin secretion was decreased in our beta cells. Interestingly, translocon inhibition by chronic anisomycin treatment prevented dysfunctions induced by palmitate, avoiding reticular calcium depletion, ER stress and restoring insulin secretion. Our results provide for the first time compelling evidence that translocon actively participates to the palmitate-induced ER calcium leak and insulin secretion decrease in beta cells. Its inhibition reduces these lipotoxic effects. Taken together, our data indicate that TLC may be a new potential target for the treatment of type 2 diabetes. PMID- 26862744 TI - Knowledge, Attitudes, and Acceptability of Pre-Exposure Prophylaxis among Individuals Living with HIV in an Urban HIV Clinic. AB - INTRODUCTION: Pre-exposure prophylaxis (PrEP) is an effective tool to reduce HIV transmission. The primary objective of this study was to assess awareness of PrEP by individuals living with HIV (HIV+) and acceptance of its use for their HIV negative (HIV-) partners. METHODS: A cross sectional survey was conducted among individuals living with HIV who received care at an urban HIV clinic between January 2013 and June 2013. The survey examined knowledge, attitudes, and acceptability of PrEP, and perception of transmission risk of HIV. Chi-Square test and Fisher's Exact test were used to compare proportions. RESULTS: Among 206 subjects living with HIV, 15.3% (32) had heard of PrEP. Men who have sex with men (MSM) were more likely to be aware of PrEP than all others (p = 0.003). Once educated about PrEP those who believed PrEP would reduce their partner's risk for HIV were more likely to recommend PrEP to their partner (p<0.001). 92% of all respondents said they would be "extremely likely/likely" to discuss PrEP use with their provider. Of 159 subjects whose main partner was HIV-, MSM (p = 0.007), male participants (p = 0.044), and those who were consistently taking meds (p = 0.049) were more likely to be aware of PrEP. Those who perceived they were at risk of transmitting HIV (p<0.001) and those who were consistently taking meds (0.049) were more likely to agree that PrEP could reduce the risk of HIV to their partners. CONCLUSION: This study illustrates a low awareness of PrEP but once educated the willingness of a cohort of individuals living with HIV to recommend PrEP to their partners. Our findings demonstrate the importance of providers informing their patients living with HIV about PrEP, as these persons are an underutilized link to support the uptake of PrEP by their HIV- partners. PMID- 26862746 TI - Erosion Remineralization Efficacy of Gel-to-Foam Fluoride Toothpastes in situ: A Randomized Clinical Trial. AB - This single-center, randomized, placebo-controlled, four-treatment, four-period crossover study compared the enamel remineralization effects of low- and medium abrasivity gel-to-foam toothpastes and a reference toothpaste (all 1,450 ppm fluoride as NaF) versus placebo toothpaste (0 ppm fluoride) using a short-term in situ erosion model. Subjects (n = 56) wearing a palatal appliance holding acid softened bovine enamel specimens brushed their teeth with the test toothpastes. Thereafter, the specimens were removed for analysis of percent surface microhardness recovery (%SMHR) and percent relative erosion resistance (%RER) at 2, 4, and 8 h. Both low- and medium-abrasivity gel-to-foam fluoride toothpastes and the reference toothpaste provided significantly greater %SMHR than placebo at all assessment time points (all p < 0.05). No statistically significant difference of %SMHR was observed between the fluoride treatment groups at any time point. Similarly, all fluoride products provided significantly superior %RER versus placebo (all p < 0.0001), whereas no significant difference of this parameter was noted between the fluoride treatment groups. Increasing numerical improvements of %SMHR and %RER were observed in all four treatment groups over time (2, 4, and 8 h). The present in situ model is a sensitive tool to investigate intrinsic and fluoride-enhanced rehardening of eroded enamel. All three fluoride toothpastes were more efficacious than placebo, and there were no safety concerns following single dosing in this short-term in situ model. PMID- 26862745 TI - Transgenic Overexpression of Aryl Hydrocarbon Receptor Repressor (AhRR) and AhR Mediated Induction of CYP1A1, Cytokines, and Acute Toxicity. AB - BACKGROUND: The aryl hydrocarbon receptor repressor (AhRR) is known to repress aryl hydrocarbon receptor (AhR) signaling, but very little is known regarding the role of the AhRR in vivo. OBJECTIVE: This study tested the role of AhRR in vivo in AhRR overexpressing mice on molecular and toxic end points mediated through a prototypical AhR ligand. METHODS: We generated AhRR-transgenic mice (AhRR Tg) based on the genetic background of C57BL/6J wild type (wt) mice. We tested the effect of the prototypical AhR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the expression of cytochrome P450 (CYP)1A1 and cytokines in various tissues of mice. We next analyzed the infiltration of immune cells in adipose tissue of mice after treatment with TCDD using flow cytometry. RESULTS: AhRR Tg mice express significantly higher levels of AhRR compared to wt mice. Activation of AhR by TCDD caused a significant increase of the inflammatory cytokines Interleukin (IL) 1beta, IL-6 and IL-10, and CXCL chemokines in white epididymal adipose tissue from both wt and AhRR Tg mice. However, the expression of IL-1beta, CXCL2 and CXCL3 were significantly lower in AhRR Tg versus wt mice following TCDD treatment. Exposure to TCDD caused a rapid accumulation of neutrophils and macrophages in white adipose tissue of wt and AhRR Tg mice. Furthermore we found that male AhRR Tg mice were protected from high-dose TCDD-induced lethality associated with a reduced inflammatory response and liver damage as indicated by lower levels of TCDD-induced alanine aminotransferase and hepatic triglycerides. Females from both wt and AhRR Tg mice were less sensitive than male mice to acute toxicity induced by TCDD. CONCLUSION: In conclusion, the current study identifies AhRR as a previously uncharacterized regulator of specific inflammatory cytokines, which may protect from acute toxicity induced by TCDD. CITATION: Vogel CF, Chang WL, Kado S, McCulloh K, Vogel H, Wu D, Haarmann-Stemmann T, Yang GX, Leung PS, Matsumura F, Gershwin ME. 2016. Transgenic overexpression of aryl hydrocarbon receptor repressor (AhRR) and AhR-mediated induction of CYP1A1, cytokines, and acute toxicity. Environ Health Perspect 124:1071-1083; http://dx.doi.org/10.1289/ehp.1510194. PMID- 26862748 TI - Cutaneous Leishmaniasis: An Overlooked Etiology of Midfacial Destructive Lesions. AB - BACKGROUND: Midline destructive lesions of the face (MDL) have a wide range of etiologies. Cutaneous Leishmaniasis (CL) is rarely reported as a possible cause. METHODS: Fifteen patients with solitary nasal lesions caused by CL were studied. The clinical data, biopsies/scrapings and PCR were collected/performed. Ridley's Pattern (RP) and Parasitic Index (PI) were documented. RESULTS: Patients' age ranged from 1 to 60 years including 7 males and 8 females. The duration of the observed lesions ranged from 1 to 18 months. Clinically, the lesions showed 6 patterns varying from dermal erythematous papulonodular with no epidermal changes to destructive erythematous plaque with massive central hemorrhagic crust. The clinical impression ranged from neoplastic to inflammatory processes. RP varied among the cases [RP 3 (n = 6), RP 4 (n = 3), RP 5 (n = 6)]. All cases show low PI [PI 0 (n = 7), PI 1 (n = 6), PI 2 (n = 1), and PI 3 (n = 1)]. Higher PI was noted in the pediatric group [average age 24 years for PI 0-1 vs. 6.5 years for PI 2 3]. Molecular speciation showed Leishmania tropica (n = 13) and Leishmania major (n = 2). All the patients received Meglumine Antimoniate (Glucantine) injections and had initial cure defined as complete scarring and disappearance of inflammatory signs within 3 months. CONCLUSION: Leishmaniasis may cause MDL especially in endemic areas. PCR is instrumental in confirming the diagnosis. MDL caused by CL showed wide spectrum of clinical and microscopic presentation. PMID- 26862747 TI - A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3. AB - The IRF3 transcription factor is critical for the first line of defense against pathogens mainly through interferon beta and antiviral gene expression. A detailed analysis of IRF3 activation is essential to understand how pathogens induce or evade the innate antiviral response. Distinct activated forms of IRF3 can be distinguished based on their phosphorylation and monomer vs dimer status. In vivo discrimination between the different activated species of IRF3 can be achieved through the separation of IRF3 phosphorylated forms based on their mobility shifts on SDS-PAGE. Additionally, the levels of IRF3 monomer and dimer can be monitored using non-denaturing electrophoresis. Here, we detail a procedure to reach the highest resolution to gain the most information regarding IRF3 activation status. This is achieved through the combination of a high resolution SDS-PAGE and a native-PAGE coupled to immunoblots using multiple total and phosphospecific antibodies. This experimental strategy constitutes an affordable and sensitive approach to acquire all the necessary information for a complete analysis of the phosphorylation-mediated activation of IRF3. PMID- 26862749 TI - Sustained Effects of Developmental Exposure to Ethanol on Zebrafish Anxiety-Like Behaviour. AB - In zebrafish developmentally exposed to ambient ethanol (20mM-50mM) 1-9 days post fertilization (dpf), the cortisol response to stress has been shown to be significantly attenuated in larvae, juveniles and 6 month old adults. These data are somewhat at variance with similar studies in mammals, which often show heightened stress responses. To test whether these cortisol data correlate with behavioural changes in treated animals, anxiety-like behaviour of zebrafish larvae (9dpf and 10dpf) and juveniles (23dpf) was tested in locomotor assays designed to this end. In open field tests treated animals were more exploratory, spending significantly less time at the periphery of the arena. Behavioural effects of developmental exposure to ethanol were sustained in 6-month-old adults, as judged by assessment of thigmotaxis, novel tank diving and scototaxis. Like larvae and juveniles, developmentally treated adults were generally more exploratory, and spent less time at the periphery of the arena in thigmotaxis tests, less time at the bottom of the tank in the novel tank diving tests, and less time in the dark area in scototaxis tests. The conclusion that ethanol exposed animals showed less anxiety-like behaviour was validated by comparison with the effects of diazepam treatment, which in thigmotaxis and novel tank diving tests had similar effects to ethanol pretreatment. There is thus a possible link between the hypophyseal-pituitary-interrenal axis and the behavioural actions of developmental ethanol exposure. The mechanisms require further elucidation. PMID- 26862750 TI - Do Menstrual Hygiene Management Interventions Improve Education and Psychosocial Outcomes for Women and Girls in Low and Middle Income Countries? A Systematic Review. AB - BACKGROUND: Unhygienic and ineffective menstrual hygiene management has been documented across low resource contexts and linked to negative consequences for women and girls. OBJECTIVES: To summarise and critically appraise evidence for the effectiveness of menstruation management interventions in improving women and girls' education, work and psychosocial wellbeing in low and middle income countries. METHODS: Structured systematic searches were conducted in peer reviewed and grey literature to identify studies evaluating education and resource provision interventions for menstruation management. Individual and cluster randomised controlled trials were eligible for inclusion, as were non randomised controlled trials. Study characteristics, outcomes and risk of bias were extracted using a piloted form. Risk of bias was independently assessed by two researchers. RESULTS: Eight studies described in ten citations were eligible for inclusion. Studies were highly heterogeneous in design and context. Six included assessment of education-only interventions, and three provided assessment of the provision of different types of sanitary products (menstrual cups, disposable sanitary pads, and reusable sanitary pads). A moderate but non significant standardised mean difference was found for the two studies assessing the impact of sanitary pad provision on school attendance: 0.49 (95%CI -0.13, 1.11). Included studies were heterogeneous with considerable risk of bias. Trials of education interventions reported positive impacts on menstrual knowledge and practices, however, many studies failed to assess other relevant outcomes. No trials assessed or reported harms. CONCLUSIONS: There is insufficient evidence to establish the effectiveness of menstruation management interventions, although current results are promising. Eight trials have been conducted, but a high risk of bias was found and clinical heterogeneity precluded synthesis of most results. Whilst trials provided some indication of positive results, further research is needed to establish the role of menstruation hygiene management in education performance, employment and other psychosocial outcomes. This review provides a concise summary of present trials and highlights improvements for future work. PMID- 26862751 TI - Plant ER geometry and dynamics: biophysical and cytoskeletal control during growth and biotic response. AB - The endoplasmic reticulum (ER) is an intricate and dynamic network of membrane tubules and cisternae. In plant cells, the ER 'web' pervades the cortex and endoplasm and is continuous with adjacent cells as it passes through plasmodesmata. It is therefore the largest membranous organelle in plant cells. It performs essential functions including protein and lipid synthesis, and its morphology and movement are linked to cellular function. An emerging trend is that organelles can no longer be seen as discrete membrane-bound compartments, since they can physically interact and 'communicate' with one another. The ER may form a connecting central role in this process. This review tackles our current understanding and quantification of ER dynamics and how these change under a variety of biotic and developmental cues. PMID- 26862752 TI - Robust Unidirectional Airflow through Avian Lungs: New Insights from a Piecewise Linear Mathematical Model. AB - Avian lungs are remarkably different from mammalian lungs in that air flows unidirectionally through rigid tubes in which gas exchange occurs. Experimental observations have been able to determine the pattern of gas flow in the respiratory system, but understanding how the flow pattern is generated and determining the factors contributing to the observed dynamics remains elusive. It has been hypothesized that the unidirectional flow is due to aerodynamic valving during inspiration and expiration, resulting from the anatomical structure and the fluid dynamics involved, however, theoretical studies to back up this hypothesis are lacking. We have constructed a novel mathematical model of the airflow in the avian respiratory system that can produce unidirectional flow which is robust to changes in model parameters, breathing frequency and breathing amplitude. The model consists of two piecewise linear ordinary differential equations with lumped parameters and discontinuous, flow-dependent resistances that mimic the experimental observations. Using dynamical systems techniques and numerical analysis, we show that unidirectional flow can be produced by either effective inspiratory or effective expiratory valving, but that both inspiratory and expiratory valving are required to produce the high efficiencies of flows observed in avian lungs. We further show that the efficacy of the inspiratory and expiratory valving depends on airsac compliances and airflow resistances that may not be located in the immediate area of the valving. Our model provides additional novel insights; for example, we show that physiologically realistic resistance values lead to efficiencies that are close to maximum, and that when the relative lumped compliances of the caudal and cranial airsacs vary, it affects the timing of the airflow across the gas exchange area. These and other insights obtained by our study significantly enhance our understanding of the operation of the avian respiratory system. PMID- 26862753 TI - Leader-Containing Uncapped Viral Transcript Activates RIG-I in Antiviral Stress Granules. AB - RIG-I triggers antiviral responses by recognizing viral RNA (vRNA) in the cytoplasm. However, the spatio-temporal dynamics of vRNA sensing and signal transduction remain elusive. We investigated the time course of events in cells infected with Newcastle disease virus (NDV), a non-segmented negative-strand RNA virus. RIG-I was recruited to viral replication complexes (vRC) and triggered minimal primary type I interferon (IFN) production. RIG-I subsequently localized to antiviral stress granules (avSG) induced after vRC formation. The inhibition of avSG attenuated secondary IFN production, suggesting avSG as a platform for efficient vRNA detection. avSG selectively captured positive-strand vRNA, and poly(A)+ RNA induced IFN production. Further investigations suggested that uncapped vRNA derived from read-through transcription was sensed by RIG-I in avSG. These results highlight how viral infections stimulate host stress responses, thereby selectively recruiting uncapped vRNA to avSG, in which RIG-I and other components cooperate in an efficient antiviral program. PMID- 26862754 TI - Predictive Role of Functional Visceral Fat Activity Assessed by Preoperative F-18 FDG PET/CT for Regional Lymph Node or Distant Metastasis in Patients with Colorectal Cancer. AB - OBJECTIVES: To investigate the role of functional visceral fat activity assessed by preoperative F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in colorectal cancer (CRC) for predicting regional lymph node (LN) or distant metastasis. METHOD: We evaluated 131 patients with newly diagnosed CRC. They all underwent pre-operative 18F-FDG PET/CT and surgery. Functional fat activity was measured by maximum standardized uptake value (SUVmax) using 18F-FDG PET/CT. Functional visceral fat activity was measured by SUVmax of visceral fat/SUVmax of subcutaneous fat (V/S) ratio. Mann-Whitney U test, chi2 test, Fisher's exact test, receiver-operating characteristic (ROC) analysis, Spearrman's correlation coefficient, and uni- and multivariate logistic regression statistical analyses were done. RESULTS: Patients with higher V/S ratio displayed a significantly higher rate of regional LN (p = 0.004) and distant metastasis (p<0.001). In addition, V/S ratio was the only factor that was significantly associated with distant metastasis. An optimal cut-off V/S ratio of 1.88 was proposed for predicting distant metastasis with a sensitivity of 84.6% and specificity of 78.8% (area under the curve: 0.86; p<0.0001). CONCLUSION: Functional visceral fat activity is significantly associated with distant metastasis in CRC patients. Furthermore, V/S ratio can be useful as a complementary factor in predicting distant metastasis. PMID- 26862755 TI - Conditional Expression of the Androgen Receptor Increases Susceptibility of Bladder Cancer in Mice. AB - Bladder cancer represents a significant human tumor burden, accounting for about 7.7% and 2.4% of all cancer cases in males and females, respectively. While men have a higher risk of developing bladder cancer, women tend to present at a later stage of disease and with more aggressive tumors. Previous studies have suggested a promotional role of androgen signaling in enhancing bladder cancer development. To directly assess the role of androgens in bladder tumorigenesis, we have developed a novel transgenic mouse strain, R26hARLoxP/+:Upk3aGCE/+, in which the human AR transgene is conditionally expressed in bladder urothelium. Intriguingly, both male and female R26hARLoxP/+:Upk3aGCE/+ mice display a higher incidence of urothelial cell carcinoma (UCC) than the age and sex matched control littermates in response to the carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). We detect expression of the human AR transgene in CK5-positive and p63 positive basal cells in bladder urothelium. Further analyses of UCC tissues from R26hARLoxP/+:Upk3aGCE/+ mice showed that the majority of tumor cells are of urothelial basal cell origin. Positive immunostaining of transgenic AR protein was observed in the majority of tumor cells of the transgenic mice, providing a link between transgenic AR expression and oncogenic transformation. We observed an increase in Ki67 positive cells within the UCC lesions of transgenic AR mice. Manipulating endogenous androgen levels by castration and androgen supplementation directly affected bladder tumor development in male and female R26hARLoxP/+:Upk3aGCE/+ mice, respectively. Taken together, our data demonstrate for the first time that conditional activation of transgenic AR expression in bladder urothelium enhances carciongen-induced bladder tumor formation in mice. This new AR transgenic mouse line mimics certain features of human bladder cancer and can be used to study bladder tumorigenesis and for drug development. PMID- 26862757 TI - RGD-Targeted Ultrasound Contrast Agent for Longitudinal Assessment of Hep-2 Tumor Angiogenesis In Vivo. AB - OBJECTIVE: To prepare arginine-glycine-aspartate (RGD)-targeted ultrasound contrast microbubbles (MBs) and explore the feasibility of their use in assessing dynamic changes in alphavbeta3 integrin expression in a murine model of tumor angiogenesis. METHODS: RGD peptides were conjugated to the surfaces of microbubbles via biotin-avidin linkage. Microbubbles bearing RADfK peptides were prepared as controls. The RGD-MBs were characterized using an Accusizer 780 and optical microscopy. The binding specificity of the RGD-MBs for alphanubeta3 expressing endothelial cells (bEnd.3) was demonstrated in vitro by a competitive inhibition experiment. In an in vivo study, mice bearing tumors of three different stages were intravenously injected with RGD-MBs and subjected to targeted, contrast-enhanced, high-frequency ultrasound. Subsequently, tumors were harvested and sectioned for immunofluorescence analysis of alphanubeta3 expression. RESULTS: The mean size of the RGD-MBs was 2.36 +/- 1.7 MUm. The RGD MBs showed significantly higher adhesion levels to bEnd.3 cells compared to control MBs (P < 0.01). There was rarely binding of RGD-MBs to alphavbeta3 negative MCF-7 cells. Adhesion of the RGD-MBs to the bEnd.3 cells was significantly inhibited following treatment with anti-alpha(v) antibodies. The quantitative acoustic video intensity for high-frequency, contrast-enhanced ultrasound imaging of subcutaneous human laryngeal carcinoma (Hep-2) tumor xenografts was significantly higher in small tumors (19.89 +/- 2.49) than in medium tumors (11.25 +/- 2.23) and large tumors (3.38 +/- 0.67) (P < 0.01). CONCLUSIONS: RGD-MBs enable noninvasive in vivo visualization of changes in tumor angiogenesis during tumor growth in subcutaneous cancer xenografts. PMID- 26862756 TI - Effects of Peroxisome Proliferator-Activated Receptor-delta Agonist on Cardiac Healing after Myocardial Infarction. AB - Peroxisome proliferator-activated receptor-delta (PPAR-delta)-dependent signaling is associated with rapid wound healing in the skin. Here, we investigated the therapeutic effects of PPAR-delta-agonist treatment on cardiac healing in post myocardial infarction (MI) rats. Animals were assigned to the following groups: sham-operated control group, left anterior descending coronary artery ligation (MI) group, or MI with administration of the PPAR-delta agonist GW610742 group. GW610742 (1 mg/kg) was administrated intraperitoneally after the operation and repeated every 3 days. Echocardiographic data showed no differences between the two groups in terms of cardiac function and remodeling until 4 weeks. However, the degrees of angiogenesis and fibrosis after MI were significantly higher in the GW610742-treated rats than in the untreated MI rats at 1 week following MI, which changes were not different at 2 weeks after MI. Naturally, PPAR-delta expression in infarcted myocardium was highest increased in 3 day after MI and then disappeared in 14 day after MI. GW610742 increased myofibroblast differentiation and transforming growth factor-beta 2 expression in the infarct zone at 7 days after MI. GW610742 also increased bone marrow-derived mesenchymal stem cell (MSC) recruitment in whole myocardium, and increased serum platelet derived growth factor B, stromal-derived factor-1 alpha, and matrix metallopeptidase 9 levels at day 3 after MI. PPAR-delta agonists treatment have the temporal effect on early fibrosis of infarcted myocardium, which might not sustain the functional and structural beneficial effect. PMID- 26862758 TI - TLR4 and TLR7/8 Adjuvant Combinations Generate Different Vaccine Antigen-Specific Immune Outcomes in Minipigs when Administered via the ID or IN Routes. AB - The induction of high levels of systemic and mucosal humoral immunity is a key goal for many prophylactic vaccines. However, adjuvant strategies developed in mice have often performed poorly in the clinic. Due to their closer similarity to humans, minipigs may provide a more accurate picture of adjuvant performance. Based on their complementary signalling pathways, we assessed humoral immune responses to model antigens after co-administration with the toll-like receptor 4 (TLR4) stimulator glucopyranosyl lipid adjuvant (GLA-AF) or the TLR7/8 agonist resiquimod (R848) (alone and in combination) via the intradermal (ID), intranasal (IN) or combined routes in the Gottingen minipig animal model. Surprisingly, we discovered that while GLA-AF additively enhanced the adjuvant effect of R848 when injected ID, it abrogated the adjuvant activity of R848 after IN inoculation. We then performed a route comparison study using a CN54 gp140 HIV Envelope model antigen adjuvanted with R848 + GLA-AF (ID) or R848 alone (IN). Animals receiving priming inoculations via one route were then boosted by the alternate route. Although differences were observed in the priming phase (IN or ID), responses converged upon boosting by the alternative route with no observable impact resultant from the order of administration (ID/IN vs IN/ID). Specific IgG responses were measured at a distal mucosal site (vaginal), although there was no evidence of mucosal linkage as these closely reflected serum antibody levels. These data indicate that the complex in vivo cross-talk between innate pathways are likely tissue specific and cannot be predicted by simple in vitro models. PMID- 26862759 TI - NPs/NPRs Signaling Pathways May Be Involved in Depression-Induced Loss of Gastric ICC by Decreasing the Production of mSCF. AB - It is well known that natriuretic peptides (NPs) are involved in the regulation of gastrointestinal motility. Interstitial cells of Cajal (ICC) are the pacemaker cells of gastrointestinal motility and gastrointestinal dyskinesia is one of the important digestive tract symptoms of depression. However, it is unclear whether they are involved in depression-induced loss of ICC. The aim of the present study was to investigate the relationship between the natriuretic peptide signaling pathway and depression-induced loss of gastric ICC in depressed rats. These results showed that the expression of c-kit and stem cell factor (SCF) in smooth muscle layers of stomach were down-regulated in depressed rats at the mRNA and protein levels. The expression of natriuretic peptide receptor (NPR)-A, B and C were up-regulated in the stomach of depressed rats at the mRNA and protein levels. NPR-A, B and C can significantly decrease the expression of SCF to treat cultured gastric smooth muscle cells (GSMCs) obtained from normal rats with different concentrations of C-type natriuretic peptide (CNP). Pretreatment of cultured GSMCs with 8-Brom-cGMP (8-Br-cGMP, a membrane permeable cGMP analog), cANF (a specific NPR-C agonist) and CNP (10-6 mol/L) demonstrated that 8-Br-cGMP had a similar effect as CNP, but treatment with cANF did not. The results of the methyl thiazolyl tetrazolium bromide (MTT) assay indicated that high concentrations of cANF (10-6 mol/L) restrained the proliferation of cultured GSMCs. Taken together, these results indicate that the up-regulation of the NPs/NPR-C and NPs/NPR-A, B/cGMP signaling pathways may be involved in depression induced loss of gastric ICC. PMID- 26862760 TI - A Lab Assembled Microcontroller-Based Sensor Module for Continuous Oxygen Measurement in Portable Hypoxia Chambers. AB - BACKGROUND: Hypoxia-based cell culture experiments are routine and essential components of in vitro cancer research. Most laboratories use low-cost portable modular chambers to achieve hypoxic conditions for cell cultures, where the sealed chambers are purged with a gas mixture of preset O2 concentration. Studies are conducted under the assumption that hypoxia remains unaltered throughout the 48 to 72 hour duration of such experiments. Since these chambers lack any sensor or detection system to monitor gas-phase O2, the cell-based data tend to be non uniform due to the ad hoc nature of the experimental setup. METHODOLOGY: With the availability of low-cost open-source microcontroller-based electronic project kits, it is now possible for researchers to program these with easy-to-use software, link them to sensors, and place them in basic scientific apparatus to monitor and record experimental parameters. We report here the design and construction of a small-footprint kit for continuous measurement and recording of O2 concentration in modular hypoxia chambers. The low-cost assembly (US$135) consists of an Arduino-based microcontroller, data-logging freeware, and a factory pre-calibrated miniature O2 sensor. A small, intuitive software program was written by the authors to control the data input and output. The basic nature of the kit will enable any student in biology with minimal experience in hobby electronics to assemble the system and edit the program parameters to suit individual experimental conditions. RESULTS/CONCLUSIONS: We show the kit's utility and stability of data output via a series of hypoxia experiments. The studies also demonstrated the critical need to monitor and adjust gas-phase O2 concentration during hypoxia-based experiments to prevent experimental errors or failure due to partial loss of hypoxia. Thus, incorporating the sensor microcontroller module to a portable hypoxia chamber provides a researcher a capability that was previously available only to labs with access to sophisticated (and expensive) cell culture incubators. PMID- 26862762 TI - Validity of Self-Reports of Height and Weight among the General Adult Population in Japan: Findings from National Household Surveys, 1986. AB - BACKGROUND/OBJECTIVES: Growing evidence indicates that self-reported height and weight are biased, but little is known about systematic errors in the general adult population in Japan. This study takes advantage of the unique opportunity to examine this issue provided by the 1986 National Nutrition Survey. SUBJECTS/METHODS: Individual-level data on a nationally representative sample aged 20-89 years from the National Nutrition Survey (November 1986) were merged with Comprehensive Survey of Living Conditions (September 1986) data to obtain a dataset containing both self-reported and measured data on height and weight for each person (n = 10,469). Discrepancies between self-reported and measured means of height, weight, and body mass index (BMI) were tested across measured BMI categories (<18.5, 18.5-24.9, 25.0-27.4, 27.5-29.9, and >=30.0 kg/m2), age groups (20-44, 45-64, and 65-89 years), and sexes. Reporting bias in mean BMI was decomposed into the contributions of misreporting height and weight. The sensitivity and specificity of self-reported BMI categories were estimated. RESULTS: Mean self-reported BMI was substantially underestimated in older women (P<0.001; Cohen's d, -0.4), and the major contributor to the bias was their over reported height. Mean self-reported BMI was also considerably underestimated in both men and women who were overweight and obese (P<0.001; Cohen's d, -1.0 to 0.6), due mainly to their underreported weight. In contrast, mean self-reported BMI was considerably overestimated in underweight men (P<0.001; Cohen's d, 0.5), due largely to their over-reported weight. The sensitivity of self-reported BMI categories was particularly low for individuals who had a measured BMI of 27.5 29.9 kg/m2 (40.9% for men and 26.8% for women). CONCLUSIONS: Self-reported anthropometric data were not sufficiently accurate to assert the validity of their use in epidemiological studies on the general adult population in Japan in the late 1980s. PMID- 26862761 TI - Intramammary Immunization of Pregnant Mice with Staphylococcal Protein A Reduces the Post-Challenge Mammary Gland Bacterial Load but Not Pathology. AB - Protein A, encoded by the spa gene, is one of the major immune evading MSCRAMM of S. aureus, demonstrated to be prevalent in a significant percentage of clinical bovine mastitis isolates in Australia. Given its' reported significance in biofilm formation and the superior performance of S. aureus biofilm versus planktonic vaccine in the mouse mastitis model, it was of interest to determine the immunogenicity and protective potential of Protein A as a potential vaccine candidate against bovine mastitis using the mouse mastitis model. Pregnant Balb/c mice were immunised with Protein A emulsified in an alum-based adjuvant by subcutaneous (s/c) or intramammary (i/mam) routes. While humoral immune response of mice post-immunization were determined using indirect ELISA, cell-mediated immune response was assessed by estimation of interferon-gamma (IFN-gamma) produced by protein A-stimulated splenocyte supernatants. Protective potential of Protein A against experimental mastitis was determined by challenge of immunized versus sham-vaccinated mice by i/mam route, based upon manifestation of clinical symptoms, total bacterial load and histopathological damage to mammary glands. Significantly (p<0.05) higher levels of IgG1 isotype were produced in mice immunized by the s/c route. In contrast, significantly higher levels of the antibody isotype IgG2a were produced in mice immunized by the i/mam route (p<0.05). There was significant reduction (p<0.05) in bacterial loads of the mammary glands of mice immunized by Protein A regardless of the route of immunization, with medium level of clinical symptoms observed up to day 3 post challenge. However, Protein A vaccine failed to protect immunized mice post challenge with biofilm producing encapsulated S. aureus via i/mam route, regardless of the route of immunization, as measured by the level of mammary tissue damage. It was concluded that, Protein A in its' native state was apparently not a suitable candidate for inclusion in a cell-free vaccine formulation against mastitis. PMID- 26862763 TI - Prevalence of Hypertension in HIV/AIDS Patients on Highly Active Antiretroviral Therapy (HAART) Compared with HAART-Naive Patients at the Limbe Regional Hospital, Cameroon. AB - BACKGROUND: Highly active antiretroviral therapy (HAART) has greatly reduced the morbidity and mortality of HIV/AIDS patients but has also been associated with increased metabolic complications and cardiovascular diseases. Data on the association between HAART and hypertension (HTN) in Africa are scarce. OBJECTIVES: Primarily to compare the prevalence of HTN in HIV/AIDS patients on HAART and HAART-naive patients in Limbe, Cameroon; and secondarily to assess other socio-demographic and clinical factors associated with HTN in this population. METHODS: A cross-sectional study was conducted at the Limbe Regional Hospital HIV treatment center between April and June 2013, involving 200 HIV/AIDS patients (100 on first-line HAART regimens for at least 12 months matched by age and sex to 100 HAART-naive patients). HTN was defined as a systolic blood pressure (BP) >= 140 mmHg and/or diastolic BP >= 90 mmHg. RESULTS: The prevalence of HTN in patients on HAART was twice (38%; 95% CI: 28.5-48.3) that of the HAART naive patients (19%; 95% CI, 11.8-28.1), p = 0.003. In multivariate analyses adjusted for age, gender, smoking, family history of HTN, and BMI-defined overweight, HAART was associated with HTN, the adjusted odds ratio of the HAART treated versus HAART-naive group was 2.20 (95% CI: 1.07-4.52), p = 0.032. HTN was associated with older age and male gender, in the HAART group and with BMI defined overweight in the HAART-naive group. CONCLUSION: The prevalence of hypertension in HIV/AIDS patients in Limbe stands out to be elevated, higher in patients on HAART compared to those not on treatment. Blood pressure and cardiovascular risk factors should be routinely monitored. Other factors such as diet, weight control and physical exercise should also be considered. PMID- 26862764 TI - Spatial Distributions of HIV Infection in an Endemic Area of Western Kenya: Guiding Information for Localized HIV Control and Prevention. AB - HIV is still a major health problem in developing countries. Even though high HIV risk-taking behaviors have been reported in African fishing villages, local distribution patterns of HIV infection in the communities surrounding these villages have not been thoroughly analyzed. The objective of this study was to investigate the geographical distribution patterns of HIV infection in communities surrounding African fishing villages. In 2011, we applied age- and sex-stratified random sampling to collect 1,957 blood samples from 42,617 individuals registered in the Health and Demographic Surveillance System in Mbita, which is located on the shore of Lake Victoria in western Kenya. We used these samples to evaluate existing antibody detection assays for several infectious diseases, including HIV antibody titers. Based on the results of the assays, we evaluated the prevalence of HIV infection according to sex, age, and altitude of participating households. We also used Kulldorff's spatial scan statistic to test for HIV clustering in the study area. The prevalence of HIV at our study site was 25.3%. Compared with the younger age group (15-19 years), adults aged 30-34 years were 6.71 times more likely to be HIV-positive, and the estimated HIV-positive population among women was 1.43 times larger than among men. Kulldorff's spatial scan statistic detected one marginally significant (P = 0.055) HIV-positive and one significant HIV-negative cluster (P = 0.047) in the study area. These results suggest a homogeneous HIV distribution in the communities surrounding fishing villages. In addition to individual behavior, more complex and diverse factors related to the social and cultural environment can contribute to a homogeneous distribution pattern of HIV infection outside of African fishing villages. To reduce rates of transmission in HIV-endemic areas, HIV prevention and control programs optimized for the local environment need to be developed. PMID- 26862766 TI - Fusion Patterns in the Skulls of Modern Archosaurs Reveal That Sutures Are Ambiguous Maturity Indicators for the Dinosauria. AB - The sutures of the skulls of vertebrates are generally open early in life and slowly close as maturity is attained. The assumption that all vertebrates follow this pattern of progressive sutural closure has been used to assess maturity in the fossil remains of non-avian dinosaurs. Here, we test this assumption in two members of the Extant Phylogenetic Bracket of the Dinosauria, the emu, Dromaius novaehollandiae and the American alligator, Alligator mississippiensis, by investigating the sequence and timing of sutural fusion in their skulls. As expected, almost all the sutures in the emu skull progressively close (i.e., they get narrower) and then obliterate during ontogeny. However, in the American alligator, only two sutures out of 36 obliterate completely and they do so during embryonic development. Surprisingly, as maturity progresses, many sutures of alligators become wider in large individuals compared to younger, smaller individuals. Histological and histomorphometric analyses on two sutures and one synchondrosis in an ontogenetic series of American alligator confirmed our morphological observations. This pattern of sutural widening might reflect feeding biomechanics and dietary changes through ontogeny. Our findings show that progressive sutural closure is not always observed in extant archosaurs, and therefore suggest that cranial sutural fusion is an ambiguous proxy for assessing maturity in non-avian dinosaurs. PMID- 26862767 TI - Discovery and Characterization of Biased Allosteric Agonists of the Chemokine Receptor CXCR3. AB - In this work we report a design, synthesis, and detailed functional characterization of unique strongly biased allosteric agonists of CXCR3 that contain tetrahydroisoquinoline carboxamide cores. Compound 11 (FAUC1036) is the first strongly biased allosteric agonist of CXCR3 that selectively induces weak chemotaxis and leads to receptor internalization and the beta-arrestin 2 recruitment with potency comparable to that of the chemokine CXCL11 without any activation of G proteins. A subtle structural change (addition of a methoxy group, 14 (FAUC1104)) led to a contrasting biased allosteric partial agonist that activated solely G proteins, induced chemotaxis, but failed to induce receptor internalization or beta-arrestin 2 recruitment. Concomitant structure-activity relationship studies indicated very steep structure-activity relationships, which steer the ligand bias between the beta-arrestin 2 and G protein pathway. Overall, the information presented provides a powerful platform for further development and rational design of strongly biased allosteric agonists of CXCR3. PMID- 26862769 TI - Photocontrolled Cargo Release from Dual Cross-Linked Polymer Particles. AB - Burst release of a payload from polymeric particles upon photoirradiation was engineered by altering the cross-linking density. This was achieved via a dual cross-linking concept whereby noncovalent cross-linking was provided by cyclodextrin host-guest interactions, and irreversible covalent cross-linking was mediated by continuous assembly of polymers (CAP). The dual cross-linked particles (DCPs) were efficiently infiltrated (~80-93%) by the biomacromolecule dextran (molecular weight up to 500 kDa) to provide high loadings (70-75%). Upon short exposure (5 s) to UV light, the noncovalent cross-links were disrupted resulting in increased permeability and burst release of the cargo (50 mol % within 1 s) as visualized by time-lapse fluorescence microscopy. As sunlight contains UV light at low intensities, the particles can potentially be incorporated into systems used in agriculture, environmental control, and food packaging, whereby sunlight could control the release of nutrients and antimicrobial agents. PMID- 26862770 TI - Technological Advances in the Treatment of Cancer: Combining Modalities to Optimize Outcomes. AB - The anticancer treatment modality tumor treating fields (TTFields; Optune, Novocure) use the lower frequency range of the electromagnetic spectrum to destroy tumor cells during mitosis. This treatment has been evaluated in several trials of patients with glioblastoma. In these patients, TTFields are delivered through 4 transducer arrays applied to the scalp. In a phase 3 clinical trial of patients with recurrent glioblastoma, TTFields were as effective as chemotherapy, and were associated with fewer and milder systemic toxicities. Data from a phase 3 trial in newly diagnosed glioblastoma suggested that the addition of TTFields to postoperative radiation therapy and chemotherapy represents an important advance in the management of newly diagnosed glioblastoma. Ongoing clinical trials are investigating the efficacy and safety of TTFields in other tumor types, including pancreatic cancer, mesothelioma, ovarian cancer, and non-small cell lung cancer. Other recent advances in the management of cancer have been seen with immunomodulatory therapy, including immune checkpoint inhibitors. Further study will be necessary to evaluate whether TTFields will enhance or impair other established and newly emerging therapies. PMID- 26862765 TI - Cecal Ligation and Puncture Results in Long-Term Central Nervous System Myeloid Inflammation. AB - Survivors of sepsis often experience long-term cognitive and functional decline. Previous studies utilizing lipopolysaccharide injection and cecal ligation and puncture in rodent models of sepsis have demonstrated changes in depressive-like behavior and learning and memory after sepsis, as well as evidence of myeloid inflammation and cytokine expression in the brain, but the long-term course of neuroinflammation after sepsis remains unclear. Here, we utilize cecal ligation and puncture with greater than 80% survival as a model of sepsis. We found that sepsis survivor mice demonstrate deficits in extinction of conditioned fear, but no acquisition of fear conditioning, nearly two months after sepsis. These cognitive changes occur in the absence of neuronal loss or changes in synaptic density in the hippocampus. Sepsis also resulted in infiltration of monocytes and neutrophils into the CNS at least two weeks after sepsis in a CCR2 independent manner. Cellular inflammation is accompanied by long-term expression of pro inflammatory cytokine and chemokine genes, including TNFalpha and CCR2 ligands, in whole brain homogenates. Gene expression analysis of microglia revealed that while microglia do express anti-microbial genes and damage-associated molecular pattern molecules of the S100A family of genes at least 2 weeks after sepsis, they do not express the cytokines observed in whole brain homogenates. Our results indicate that in a naturalistic model of infection, sepsis results in long-term neuroinflammation, and that this sustained inflammation is likely due to interactions among multiple cell types, including resident microglia and peripherally derived myeloid cells. PMID- 26862774 TI - Surface Enhanced Infrared Studies of 4-Methoxypyridine Adsorption on Gold Film Electrodes. AB - This work uses electrochemical surface sensitive vibrational spectroscopy to characterize the adsorption of a known metal nanoparticle stabilizer and growth director, 4-methoxypyridine (MOP). Surface enhanced infrared absorption spectroscopy (SEIRAS) is employed to study the adsorption of 4-methoxypyridine on gold films. Experiments are performed under electrochemical control and in different electrolyte acidities to identify both the extent of protonation of the adsorbed species as well as its orientation with respect to the electrode surface. No evidence of adsorbed conjugated acid is found even when the electrolyte pH is considerably lower than the pKa. Through an analysis of the transition dipole moments, determined from DFT calculations, the SEIRA spectra support an adsorption configuration through the ring nitrogen which is particularly dominant in neutral pH conditions. Adsorption is dependent on both the electrical state of the Au film electrode as well as the presence of ions in the electrolyte that compete for adsorption sites at positive potentials. Combined differential capacitance measurements and spectroscopic data demonstrate that both a horizontal adsorption geometry and a vertical adsorption phase can be induced, with the former being found on negatively charged surfaces in acidic media and the latter over a wide range of polarizations in neutral solutions. PMID- 26862775 TI - CO2 Absorption Using Fluorine Functionalized Ionic Liquids: Interplay of Hydrogen and sigma-Hole Interactions. AB - Use of ionic liquids (ILs) for CO2 capture offers certain advantages over currently used methodologies and is of growing interest. With this perspective, ILs composed of S-ethyl-N,N,N',N'-tetramethylthiouronium ([ETT]) and 1-hexyl-3 methylimidazolium ([Hmim]) cations and tris(pentafluoroethyl)trifluorophosphate ([FEP]) anion have been investigated. The present work unravels the noncovalent interactions accompanying CO2 capture by these ILs. Electronic structure of ion pairs and their CO2 absorbed [ETT][FEP].n(CO2) and [Hmim][FEP].n(CO2) (n up to 30) complexes are derived. The anisotropy in molecular electrostatic potential dictates the binding of CO2 through the interplay of (i) halogen bonding (O...F) between electron deficient sigma-holes on fluorines, (ii) electrostatic C...F interactions between electron deficient carbons of CO2 and the electron-rich fluorine atoms, and the (iii) hydrogen bonding (O...H) interactions from the cation. The manifestations of these interactions on binding energies, polarizabilities, and vibrational spectra of CO2 absorbed complexes are presented. Consequent "frequency shift" accompanying hydrogen and halogen bonding exhibit complementary characteristics in the infrared spectra of CO2 absorbed complexes. Correlation of binding energies to absorbed CO2 molecules further demonstrate that [Hmim] based ILs are more efficient for CO2 capture applications. PMID- 26862776 TI - Detection of West Nile and Usutu Viruses in Italian Free Areas: Entomological Surveillance in Piemonte and Liguria Regions, 2014. AB - West Nile virus and Usutu virus have established in different parts of Italy over the past 10 years. Piemonte and Liguria Regions (Northwestern Italy) are known to be nonendemic areas, despite the presence of competent vectors and environmental conditions conducive to maintaining infection. This work evidences for the first time, through an entomological surveillance implemented on the basis of risk factor approach, the presence of West Nile and Usutu viruses in Piemonte and Liguria Regions (Northwestern Italy). PMID- 26862778 TI - Temperature-Dependent Double Isocyanide Insertion Reaction To Construct a Polycyclic Skeleton. AB - A novel strategy to furnish selective double insertion of isocyanides with the aid of potassium tetrachloroaurate(III) has been disclosed. This strategy provides quick access to approach a complex polycyclic skeleton in an efficient manner. Unexpected oxygen migration was also observed when the reaction was conducted at a lower temperature. PMID- 26862777 TI - Angiotensin-converting enzyme inhibitor prevents oxidative stress, inflammation, and fibrosis in carbon tetrachloride-treated rat liver. AB - Hepatic fibrosis is a common feature of chronic liver injury, and the involvement of angiotensin II in such process has been studied earlier. We hypothesized that anti-angiotensin II agents may be effective in preventing hepatic fibrosis. In this study, Long Evans female rats were used and divided into four groups such as Group-I, Control; Group-II, Control + ramipril; Group-III, CCl4; and Group-IV, CCl4 + ramipril. Group II and IV are treated with ramipril for 14 d. At the end of treatment, the livers were removed, and the level of hepatic marker enzymes (aspartate aminotransferase, Alanine aminotransferase, and alkaline phosphatase), nitric oxide, advanced protein oxidation product , catalase activity, and lipid peroxidation were determined. The degree of fibrosis was evaluated through histopathological staining with Sirius red and trichrome milligan staining. Carbon-tetrachloride (CCl4) administration in rats developed hepatic dysfunction and raised the hepatic marker enzymes activities significantly. CCl4 administration in rats also produced oxidative stress, inflammation, and fibrosis in liver. Furthermore, angiotensinogen-inhibitor ramipril normalized the hepatic enzymes activities and improved the antioxidant enzyme catalase activity. Moreover, ramipril treatment ameliorated lipid peroxidation and hepatic inflammation in CCl4-treated rats. Ramipril treatment also significantly reduced hepatic fibrosis in CCl4-administered rats. In conclusion, our investigation suggests that the antifibrotic effect of ramipril may be attributed to inhibition of angiotensin-II mediated oxidative stress and inflammation in liver CCl4 administered rats. PMID- 26862779 TI - Recent Discoveries and Future Challenges in Atmospheric Organic Chemistry. AB - Earth's atmosphere contains a multitude of organic compounds, which differ by orders of magnitude regarding fundamental properties such as volatility, reactivity, and propensity to form cloud droplets, affecting their impact on global climate and human health. Despite recent major research efforts and advances, there are still substantial gaps in understanding of atmospheric organic chemistry, hampering efforts to understand, model, and mitigate environmental problems such as aerosol formation in both polluted urban and more pristine regions. The analytical toolbox available for chemists to study atmospheric organic components has expanded considerably during the past decade, opening new windows into speciation, time resolution and detection of reactive and semivolatile compounds at low concentrations. This has provided unprecedented opportunities, but also unveiled new scientific challenges. Specific groundbreaking examples include the role of epoxides in aerosol formation especially from isoprene, the importance of highly oxidized, reactive organics in air-surface processes (whether atmosphere-biosphere exchange or aerosols), as well as the extent of interactions of anthropogenic and biogenic emissions and the resulting impact on atmospheric organic chemistry. PMID- 26862782 TI - Parental Perspectives of Communication at the End of Life at a Pediatric Oncology Institution. AB - BACKGROUND: The interaction of health care providers and hospital staff with patients and families at the end of life affects the parental grief experience. Both verbal and nonverbal communication are key components of this interaction. OBJECTIVE: The study objective was to explore the communication between hospital staff members and patients and families at the time of patients' health decline near the end of life. METHODS: Twelve bereaved parents participated in a focus group. Semantic content analysis was used to analyze the transcript. RESULTS: Parents' responses to the prompt about typical ways the medical team communicated yielded 109 codes, which were grouped into 12 themes. The most common themes were "patient inclusion" and "explanation of medical plan," both used in 17% of responses. Responses to the prompt about positive and negative aspects of communication generated 208 codes, yielding 15 different themes. The most common theme about positive communication was the "strong relationship between family and staff." The theme "variations in care with a negative impact" was used most frequently in describing negative communication. CONCLUSION: This study helps to identify techniques that should be used by clinicians as they work with children with cancer and their families, particularly including patients in treatment decisions, ongoing relationship building, communicating with caring and empathy, using an interdisciplinary team for additional support, and pairing bad news with a plan of action. PMID- 26862781 TI - How Acidic Is Carbonic Acid? AB - Carbonic, lactic, and pyruvic acids have been generated in aqueous solution by the transient protonation of their corresponding conjugate bases by a tailor-made photoacid, the 6-hydroxy-1-sulfonate pyrene sodium salt molecule. A particular goal is to establish the pK(a) of carbonic acid H2CO3. The on-contact proton transfer (PT) reaction rate from the optically excited photoacid to the carboxylic bases was derived, with unprecedented precision, from time-correlated single-photon-counting measurements of the fluorescence lifetime of the photoacid in the presence of the proton acceptors. The time-dependent diffusion-assisted PT rate was analyzed using the Szabo-Collins-Kimball equation with a radiation boundary condition. The on-contact PT rates were found to follow the acidity order of the carboxylic acids: the stronger was the acid, the slower was the PT reaction to its conjugate base. The pK(a) of carbonic acid was found to be 3.49 +/- 0.05 using both the Marcus and Kiefer-Hynes free energy correlations. This establishes H2CO3 as being 0.37 pK(a) units stronger and about 1 pK(a) unit weaker, respectively, than the physiologically important lactic and pyruvic acids. The considerable acid strength of intact carbonic acid indicates that it is an important protonation agent under physiological conditions. PMID- 26862783 TI - Catalytic Cage Formation via Controlled Dimerization of Norbornadienes: An Entry to Functionalized HCTDs (Heptacyclo[6.6.0.0(2,6).0(3,13).0(4,11).0(5,9).0(10,14)]tetradecanes). AB - A general and practical catalytic method has been developed for the rapid synthesis of HCTD (heptacyclo[6.6.0.0(2,6).0(3,13).0(4,11).0(5,9).0(10,14)]tetradecanes) and various new 7,12-disubstituted HCTDs from norbornadienes. Compared to the known approaches, this new protocol avoids stoichiometric metals, utilizes commercially available reagents as catalysts, and affords higher yields and significantly improved selectivity. In addition, quadracyclane was discovered for the first time to undergo a similar endo,cis,endo cycloaddition to give HCTD in a good yield. Derivatization of HCTDs led to efficient preparation of a range of novel homo- and heterobifunctional scaffolds that hold potentials for biological and material applications. PMID- 26862780 TI - Nanomanufacturing: A Perspective. AB - Nanomanufacturing, the commercially scalable and economically sustainable mass production of nanoscale materials and devices, represents the tangible outcome of the nanotechnology revolution. In contrast to those used in nanofabrication for research purposes, nanomanufacturing processes must satisfy the additional constraints of cost, throughput, and time to market. Taking silicon integrated circuit manufacturing as a baseline, we consider the factors involved in matching processes with products, examining the characteristics and potential of top-down and bottom-up processes, and their combination. We also discuss how a careful assessment of the way in which function can be made to follow form can enable high-volume manufacturing of nanoscale structures with the desired useful, and exciting, properties. PMID- 26862785 TI - Antiapoptotic Effect of Recombinant HMGB1 A-box Protein via Regulation of microRNA-21 in Myocardial Ischemia-Reperfusion Injury Model in Rats. AB - The ~80 amino acid A box DNA-binding domain of high mobility group box 1 (HMGB1) protein antagonizes proinflammatory responses during myocardial ischemia reperfusion (I/R) injury. The exact role of microRNA-21 (miR-21) is unknown, but its altered levels are evident in I/R injury. This study examined the roles of HMGB1 A-box and miR-21 in rat myocardial I/R injury model. Sixty Sprague-Dawley rats were randomly divided into six equal groups: (1) Sham; (2) I/R; (3) Ischemic postconditioning (IPost); (4) AntagomiR-21 post-treatment; (5) Recombinant HMGB1 A-box pretreatment; and (6) Recombinant HMGB1 A-box + antagomiR-21 post treatment. Hemodynamic indexes, arrhythmia scores, ischemic area and infarct size, myocardial injury, and related parameters were studied. Expression of miR 21 was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was used to quantify apoptosis. Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of pressure rise (+dp/dtmax), and decline (-dp/dtmax) showed clear reduction upon treatment with recombinant HMGB1 A-box. Arrhythmia was relieved and infarct area decreased in the group pretreated with recombinant HMGB1 A-box, compared with other groups. Circulating lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels increased in response to irreversible cellular injury, while creatine kinase MB isoenzymes (CK-MB) and superoxide dismutase (SOD) activities were reduced in the I/R group, which was reversed following recombinant HMGB1 A-box treatment. Interestingly, pretreatment with recombinant HMGB1 A-box showed the most dramatic reductions in miR-21 levels, compared with other groups. Significantly reduced apoptotic index (AI) was seen in recombinant HMGB1 A-box pretreatment group and recombinant HMGB1 A-box + antagomiR-21 post-treatment group, with the former showing a more dramatic lowering in AI than the latter. Bax, caspase-8, and CHOP showed reduced expression, and Bcl-2 and p-AKT levels were upregulated in recombinant HMGB1 A-box pretreatment group. Thus, recombinant HMGB1 A-box treatment protects against I/R injury and the mechanisms may involve inhibition of miR-21 expression. PMID- 26862786 TI - Comparison of brachial dilatory responses to hypercapnia and reactive hyperemia. AB - Flow-mediated dilation (FMD) relies on reactive hyperemia to stimulate the endothelium to release nitric oxide, causing smooth muscle relaxation. Hypercapnia also produces vasodilation, which is thought to be nitric oxide independent. The purpose of this study was to compare and contrast the effects of hypercapnia and reactive hyperemia as stimuli for brachial artery dilation. On separate days, twenty-five participants underwent vasodilation studies via reactive hyperemia or hypercapnia (i.e. 10 mmHg increase in end-tidal carbon dioxide [PetCO2)]). During both studies changes in brachial artery diameter were recorded using continuous ultrasound imaging. Heart rate (HR) was measured throughout both tests. Resting HR (63 +/- 11 versus 68 +/- 14 beats min(-1), p = 0.0027) and baseline brachial artery diameter measurements (4.57 +/- 1.51 versus 5.28 +/- 1.86 mm, p = 0.022) were significantly different between reactive hyperemia and hypercapnia, respectively. HR at peak dilation (65 +/- 11 versus 76 +/- 14 beats min(-1), p < 0.0001), peak vessel dilation (8.68 +/- 4.50 versus 5.28 +/- 1.86%, p = 0.002), and time to peak dilation (90.8 +/- 120.1 versus 658.3 +/- 226.6 s, p < 0.0001) were also significantly different between reactive hyperemia and hypercapnia. The dynamics by which reactive hyperemia and hypercapnia stimulate vasodilation appear to differ. Hypercapnia produces a smaller and slower vasodilatory effect than reactive hyperemia. Further research is necessary to better understand the mechanisms of vasodilation under hypercapnic conditions. PMID- 26862787 TI - Stable water isotopic composition of the Antarctic subglacial Lake Vostok: implications for understanding the lake's hydrology. AB - We estimated the stable isotopic composition of water from the subglacial Lake Vostok using two different sets of samples: (1) water frozen on the drill bit immediately after the first lake unsealing and (2) water frozen in the borehole after the unsealing and re-drilled one year later. The most reliable values of the water isotopic composition are: -59.0 +/- 0.3 0/00 for oxygen-18, -455 +/- 1 0/00 for deuterium and 17 +/- 1 0/00 for d-excess. This result is also confirmed by the modelling of isotopic transformations in the water which froze in the borehole, and by a laboratory experiment simulating this process. A comparison of the newly obtained water isotopic composition with that of the lake ice (-56.2 0/00 for oxygen-18, -442.4 0/00 for deuterium and 7.2 0/00 for d-excess) leads to the conclusion that the lake ice is very likely formed in isotopic equilibrium with water. In turn, this means that ice is formed by a slow freezing without formation of frazil ice crystals and/or water pockets. This conclusion agrees well with the observed physical and chemical properties of the lake's accreted ice. However, our estimate of the water's isotopic composition is only valid for the upper water layer and may not be representative for the deeper layers of the lake, so further investigations are required. PMID- 26862784 TI - A Chronic Obstructive Pulmonary Disease Susceptibility Gene, FAM13A, Regulates Protein Stability of beta-Catenin. AB - RATIONALE: A genetic locus within the FAM13A gene has been consistently associated with chronic obstructive pulmonary disease (COPD) in genome-wide association studies. However, the mechanisms by which FAM13A contributes to COPD susceptibility are unknown. OBJECTIVES: To determine the biologic function of FAM13A in human COPD and murine COPD models and discover the molecular mechanism by which FAM13A influences COPD susceptibility. METHODS: Fam13a null mice (Fam13a(-/-)) were generated and exposed to cigarette smoke. The lung inflammatory response and airspace size were assessed in Fam13a(-/-) and Fam13a(+/+) littermate control mice. Cellular localization of FAM13A protein and mRNA levels of FAM13A in COPD lungs were assessed using immunofluorescence, Western blotting, and reverse transcriptase-polymerase chain reaction, respectively. Immunoprecipitation followed by mass spectrometry identified cellular proteins that interact with FAM13A to reveal insights on FAM13A's function. MEASUREMENTS AND MAIN RESULTS: In murine and human lungs, FAM13A is expressed in airway and alveolar type II epithelial cells and macrophages. Fam13a null mice (Fam13a(-/-)) were resistant to chronic cigarette smoke-induced emphysema compared with Fam13a(+/+) mice. In vitro, FAM13A interacts with protein phosphatase 2A and recruits protein phosphatase 2A with glycogen synthase kinase 3beta and beta-catenin, inducing beta-catenin degradation. Fam13a(-/-) mice were also resistant to elastase-induced emphysema, and this resistance was reversed by coadministration of a beta-catenin inhibitor, suggesting that FAM13A could increase the susceptibility of mice to emphysema development by inhibiting beta catenin signaling. Moreover, human COPD lungs had decreased protein levels of beta-catenin and increased protein levels of FAM13A. CONCLUSIONS: We show that FAM13A may influence COPD susceptibility by promoting beta-catenin degradation. PMID- 26862788 TI - Computer modelling of RF ablation in cortical osteoid osteoma: Assessment of the insulating effect of the reactive zone. AB - PURPOSE: The aim was to study by computer simulations the insulating role of the reactive zone surrounding a cortical osteoid osteoma (OO) in terms of electrical and thermal performance during radiofrequency ablation (RFA). MATERIAL AND METHODS: We modelled a cortical OO consisting of a nidus (10 mm diameter) enclosed by a reactive zone. The OO was near a layer of cortical bone 1.5 mm thick. Trabecular bone partially surrounds the OO and there was muscle around the cortical bone layer. We modelled RF ablations with a non-cooled-tip 17-gauge needle electrode (300 s duration and 90 degrees C target temperature). Sensitivity analyses were conducted assuming a reactive zone electrical conductivity value (sigmarz) within the limits of the cortical and trabecular bone, i.e. 0.02 S/m and 0.087 S/m, respectively. In this way we were really modelling the different degrees of osteosclerosis associated with the reactive zone. RESULTS: The presence of the reactive zone drastically reduced the maximum temperature reached outside it. The temperature drop was proportional to the thickness of the reactive zone: from 68 degrees C when it was absent to 44 degrees C when it is 7.5 mm thick. Higher nidus conductivity values (sigman) implied higher temperatures, while lower temperatures meant higher sigmarz values. Changing sigmarz from 0.02 S/m to 0.087 S/m reduced lesion diameters from 2.4 cm to 1.8 cm. CONCLUSIONS: The computer results suggest that the reactive zone plays the role of insulator in terms of reducing the temperature in the surrounding area. PMID- 26862789 TI - An Aluminum Dihydride Working as a Catalyst in Hydroboration and Dehydrocoupling. AB - The well-defined aluminum dihydride LAlH2 (L = HC(CMeNAr)2, Ar = 2,6-Et2C6H3) (1) operates in catalysis like a transition metal complex. The catalytic activity of 1 for hydroboration of terminal alkynes was investigated. Furthermore, catalyst 1 effectively initiated the dehydrocoupling of boranes with amines, thiols, and phenols, respectively, to form compounds with B-E bonds (E = N, S, O) under elimination of H2. Quantum mechanical calculations indicate that hydroboration and dehydrocoupling reactions occur via three consecutive cycloaddition reactions involving the activation of the X-H (X = Al, B, C, and O) sigma-bonds. PMID- 26862791 TI - Family Medicine In India. PMID- 26862792 TI - The past, present and future of patient safety education and research in primary care. AB - In the first series of related articles, we describe how assurance of patient safety in primary care was traditionally viewed by the medical profession hierarchy as being wholly dependent at the individual level upon a combination of education and training, knowledge, skill, experience and commitment to professional development. As well as summarising the evidence underpinning what we know about patient safety in primary care, we outline how contemporary thinking has evolved to recognise that the safety issue is complex, problematic and systemic, and that it is now beginning to attract the attention of national policymakers, educators and research funders in some countries. We also describe a range of recently developed educational safety concepts and methods that have been implemented as part of current national programme initiatives in the United Kingdom and internationally. Finally, we reflect on international progress on patient safety in primary care thus far; propose a future direction for related education, development and research; and briefly introduce the Human Factors based topics to be addressed in the forthcoming series of interrelated articles in this journal. PMID- 26862790 TI - Medical Management of Pediatric Malignant Bowel Obstruction in a Patient with Burkitt's Lymphoma and Ataxia Telangiectasia Using Continuous Ambulatory Drug Delivery System. AB - Malignant bowel obstruction (MBO) is commonly seen in patients with advanced abdominal cancers. The incidence of pediatric MBO in a patient with Burkitt's lymphoma and ataxia telangiectasia is rare, with no published case reports till now. Conservative management of inoperable MBO results in relief of symptoms and improves quality of life. An 11-year-old boy with Burkitt's lymphoma and ataxia telangiectasia was referred to pediatric palliative care with MBO. The objective of this report is to demonstrate conservative management of pediatric MBO using continuous ambulatory drug delivery system. The patient was initiated on continuous ambulatory drug delivery (CADD) system for symptom relief. MBO was reversed with conservative management and the child was discharged on self collapsible portable elastomeric continuous infusion pump under the supervision of a local family physician. The child remained comfortable at home for 4 weeks until his death. His parents were satisfied with the child's symptom control, quality of life, and were able to care for the child at home. In a resource limited setting, managing patients at home using elastomeric continuous infusion pumps instead of expensive automated CADD is a practical pharmacoeconomic approach. PMID- 26862793 TI - Education for rural practice in rural practice. AB - Despite the substantial differences between developing and developed countries, access is the major rural health issue. Studies in many countries have shown that the three factors most strongly associated with entering rural practice are: (1) a rural upbringing; (2) positive clinical and educational experiences in rural settings as part of undergraduate medical education; (3) targeted training for rural practice at the postgraduate level. This paper presents examples of successful rural primary care-based education in different parts of the world, then introduces the Wonca Rural Medical Education Guidebook which was launched at the 2014 Wonca Rural Health World Conference and concludes with a brief report of the 2015 conference held in Dubrovnik Croatia. PMID- 26862794 TI - Is chronic disease on the curriculum? PMID- 26862795 TI - A one-year practice-based learning programme for new general practice nurses in Scotland: evaluation of the pilot. AB - This paper summarises the evaluation of a pilot programme introduced by NHS Education for Scotland to provide education and skills training for nurses new to general practice. The programme was developed through extensive consultation with existing general practice nurses and was educationally accredited by the Royal College of General Practitioners and the Royal College of Nursing in 2013. Twelve nurses embarked upon the programme 2012-2013 and nine completed it. The programme was extensively evaluated through questionnaires (with supervisors, practice staff and participants), analysis of programme documentation and interviews with participants. Based on the evaluation feedback, alterations have been made to subsequent deliveries of the programme. These include removing some topic areas and lengthening the programme by three months. The programme continues to be successfully delivered and evaluation is ongoing to ensure it continues to meet nurses' needs. PMID- 26862796 TI - Continuity of care in general practice vocational training: prevalence, associations and implications for training. AB - Continuity of care is a defining characteristic of general practice. Practice structures may limit continuity of care experience for general practice registrars (trainees). This study sought to establish prevalence and associations of registrars' continuity of care. We performed an analysis of an ongoing cohort study of Australian registrars' clinical consultations. Primary outcome factors were 'Upstream' continuity (having seen the patient prior to the index consultation) and 'Downstream' continuity (follow-up organised post-index consultation). Independent variables were registrar, practice, patient, consultation and educational factors. 400 registrars recorded 48,114 consultations. 43% of patients had seen the registrar pre-index consultation, and 49% had follow-up organised. 'Upstream' continuity associations included registrar seniority, Australian medical qualification, practice billing policy, smaller practice size, registrar's previous training in the practice, chronic disease and older, female patients (but not registrar full-time/part-time status). Associations of 'Downstream' continuity included non-Australian qualification, billing, chronic disease and the patient having seen the registrar previously. Consultations prompting follow-up were more complex: longer duration, involving more problems and generating more learning goals. There was, however, evidence for limited educational utility of this 'continuity'. In our study, continuity of care in Australian registrars' training experience is modest. Associations are complex, but may inform initiatives to increase in-training continuity. PMID- 26862797 TI - Commentary on 'Continuity of care (CoC) in general practice vocational training: prevalence, associations and implications for training'. PMID- 26862798 TI - Do role-players affect the outcome of a high-stakes postgraduate OSCE, in terms of candidate sex or ethnicity? Results from an analysis of the 52,702 anonymised case scores from one year of the MRCGP clinical skills assessment. AB - The MRCGP clinical skills assessment (CSA), a high-stakes OSCE examination whereby GPs exit their training, uses trained role-players to depict patients (though not to mark candidates). Just as subgroups of examiners can potentially affect the results of subgroups of candidates through biases expressed in discriminatory marking, so possibly could subgroups of role-players alter the difficulty for different candidate groups. This study looks at the contribution of role-players to such possible systematic unfairness in the assessment. Using multiple linear regression, we examined the data from all 52,702 case scores from the MRCGP CSA for the academic year 2012-2013. Candidates were dichotomised by sex, by ethnicity and by source of primary medical qualification (PMQ); role players were dichotomised by sex and binary ethnicity; and the transaction of candidate/role-player encounters were classified as 'same' or 'different' in terms of the two parties' sex and of their ethnicity. Neither examiner nor role player characteristics were found to predict any statistically significant portion of case score variance, where the significant (p < .001) predictors were source of PMQ (UK or elsewhere: 11% of case score variance), candidates' ethnicity (1%), candidates' sex (0.6%) and 'transactional' sex (0.1%). We did not therefore find any substantial degree of support for the proposition that role player subgroups systematically influence candidate subgroups' scores. PMID- 26862799 TI - Are there practical opportunities for developing leadership skills during GP training and beyond? A survey of GP trainees and trainers in South East Scotland. AB - BACKGROUND: There is currently a lack of formal training in leadership skills, particularly during GP training. This study aimed to explore the current training and practical opportunities which exist, specifically exploring the views of GP trainees and trainers. METHODS: An electronic questionnaire was sent to 266 GP trainees and trainers in south-east Scotland. Questions focused on respondents' experience of leadership-specific training and opportunities to engage with leadership roles. RESULTS: There were a total of 76 respondents (28.6% response rate). Response rate was 19.0% in trainees and 34.6% in trainers. A majority of respondents (80.0%) were established GPs. Of those who had received training in leadership, most (72.1%) underwent this after qualifying as a GP. Respondents identified a range of leadership roles within and outside the practice covering clinical and non-clinical areas. Most were interested in future leadership roles (46.7% moderately interested; 28% very interested). More time, training opportunities and the presence of GP role models were motivating factors in terms of participants' readiness to take on future leadership roles. CONCLUSIONS: Signposting trainees, trainers and general practitioners to leadership opportunities and training would be relatively easy but addressing a lack of motivating factors at a local level is essential. The effectiveness of such training and opportunities for experiential learning in leadership roles requires further research. PMID- 26862800 TI - The development of a short course for general practitioners in the management of patients with medically unexplained symptoms (MUS). PMID- 26862801 TI - Enhancing empathy: a drama workshop. PMID- 26862802 TI - Memory and learning. PMID- 26862803 TI - Entrustable professional activities. PMID- 26862804 TI - Undertake research in medical education series: foreword. PMID- 26862805 TI - Turn the good idea into a feasible project. PMID- 26862808 TI - Overcoming challenges in primary care education: the why, what and how of family medicine in India. PMID- 26862809 TI - Thank you, Education for Primary Care! PMID- 26862810 TI - Attitudes toward professionalism maintained after curriculum reform. PMID- 26862811 TI - Therapeutic examination. PMID- 26862812 TI - Zika Virus and Microcephaly. PMID- 26862813 TI - Understanding the Impact of Treatment on the Dimensions of Childhood Depression. AB - BACKGROUND: Childhood depression is often chronic and recurrent, with only modest improvements after optimal treatments. Novel approaches are needed for accurate diagnosis, timely selection of the best treatment for childhood depression, and improvement of remission rates. An important part of diagnosis is to determine how many consistent dimensions underlie childhood depression and what impact treatment may have on these dimensions. OBJECTIVE: The goal of the current study is evaluate the consistency of the number of depressive symptom dimensions and examine the effect of depression treatment on the change in dimensions by seeing if this dimensional structure is the same for groups that were given a placebo and groups that were given an active drug, fluoxetine. METHODS: We examined a combined sample of three clinical trials data sets with a total of 269 placebo patients and 261 fluoxetine patients at baseline, and 253 placebo patients and 249 fluoxetine patients at exit. Principal components analysis with associated parallel analysis followed by a ProMax oblique rotation was conducted on each week's scores. The similarity of the rotated structures between treatments and between weeks was then assessed using Wrigley and Neuhaus' (1955) degree of factorial similarity measure, which is a correlation-like statistic that takes two solutions based upon the same measures and assesses how similar they are. RESULTS: Preliminary analysis indicated that mean scores of both treatment groups declined from baseline to exit, but the decline was greater for the fluoxetine group. There were four dimensions at baseline and two dimensions at exit in each treatment group. Hence the numbers of dimensions were the same in the two groups, whereas the content of the components was the same at baseline for the two groups, but was different at exit. Basically, the factorial similarities of the rotated factors were very high at baseline between the two groups for both factors (Psi = 0.97 for factor I and 0.94 for factor II) before they were treated differently. However, at exit, the respective similarities dropped to 0.58 and 0.04 for factors I and II. Therefore, time had a large effect in changing both groups' factor structure, but it was especially large when there was an active treatment. CONCLUSIONS: In comparing the baseline and exit dimensions in a forced two factor solution of two treatment groups, it was revealed that treatment did have an impact on the change in dimensions. These results further the generality of the simplification of the factor structure of the Childhood Depression Rating Scale- Revised (CDRS-R) over time. In addition, these results show the effect of time and therapy on the factor structures. The fluoxetine group followed the trend of the content of the dimensions revealed in a previous study, whereas the placebo group had a less distinct change over time. PMID- 26862814 TI - Concurrent Electroencephalography Recording During Transcranial Alternating Current Stimulation (tACS). AB - Oscillatory brain activities are considered to reflect the basis of rhythmic changes in transmission efficacy across brain networks and are assumed to integrate cognitive neural processes. Transcranial alternating current stimulation (tACS) holds the promise to elucidate the causal link between specific frequencies of oscillatory brain activity and cognitive processes. Simultaneous electroencephalography (EEG) recording during tACS would offer an opportunity to directly explore immediate neurophysiological effects of tACS. However, it is not trivial to measure EEG signals during tACS, as tACS creates a huge artifact in EEG data. Here we explain how to set up concurrent tACS-EEG experiments. Two necessary considerations for successful EEG recording while applying tACS are highlighted. First, bridging of the tACS and EEG electrodes via leaking EEG gel immediately saturates the EEG amplifier. To avoid bridging via gel, the viscosity of the EEG gel is the most important parameter. The EEG gel must be viscous to avoid bridging, but at the same time sufficiently fluid to create contact between the tACS electrode and the scalp. Second, due to the large amplitude of the tACS artifact, it is important to consider using an EEG system with a high resolution analog-to-digital (A/D) converter. In particular, the magnitude of the tACS artifact can exceed 100 mV at the vicinity of a stimulation electrode when 1 mA tACS is applied. The resolution of the A/D converter is of importance to measure good quality EEG data from the vicinity of the stimulation site. By following these guidelines for the procedures and technical considerations, successful concurrent EEG recording during tACS will be realized. PMID- 26862815 TI - Video Imaging and Spatiotemporal Maps to Analyze Gastrointestinal Motility in Mice. AB - The enteric nervous system (ENS) plays an important role in regulating gastrointestinal (GI) motility and can function independently of the central nervous system. Changes in ENS function are a major cause of GI symptoms and disease and may contribute to GI symptoms reported in neuropsychiatric disorders including autism. It is well established that isolated colon segments generate spontaneous, rhythmic contractions known as Colonic Migrating Motor Complexes (CMMCs). A procedure to analyze the enteric neural regulation of CMMCs in ex vivo preparations of mouse colon is described. The colon is dissected from the animal and flushed to remove fecal content prior to being cannulated in an organ bath. Data is acquired via a video camera positioned above the organ bath and converted to high-resolution spatiotemporal maps via an in-house software package. Using this technique, baseline contractile patterns and pharmacological effects on ENS function in colon segments can be compared over 3-4 hr. In addition, propagation length and speed of CMMCs can be recorded as well as changes in gut diameter and contraction frequency. This technique is useful for characterizing gastrointestinal motility patterns in transgenic mouse models (and in other species including rat and guinea pig). In this way, pharmacologically induced changes in CMMCs are recorded in wild type mice and in the Neuroligin-3(R451C) mouse model of autism. Furthermore, this technique can be applied to other regions of the GI tract including the duodenum, jejunum and ileum and at different developmental ages in mice. PMID- 26862816 TI - Effect of a Single Nucleotide Polymorphism in the LAMA1 Promoter Region on Transcriptional Activity: Implication for Pathological Myopia. AB - PURPOSE: To elucidate the role of the protein coding laminin alpha1 (LAMA1) gene in pathological myopia (PM) at the transcriptional level. To achieve this, the binding affinity of single nucleotide polymorphism (SNP) rs2089760-located on the LAMA1 promoter gene-to human fetal scleral fibroblast (HFSF) nucleoprotein was investigated and its effect on LAMA1 transcriptional initiation activity was analyzed. METHODS: Binding interactions of the HFSF nucleoprotein and biotin labeled SNP rs2089760 probe were investigated by amplifying the LAMA1 promoter gene and performing overlap extension polymerase chain reaction (PCR) to obtain the G/A mutation of LAMA1 SNP rs2089760. Recombinant adenovirus vectors, Ad5f11p pLAMA1SNPa-Luc2, Ad5f11p-pLAMA1SNPg-Luc2, and Ad5f11p-CMV-RLuc, were constructed. Fluorescence intensity ratios of firefly luciferase (FLuc) and renilla luciferase (RLuc) vectors were measured 48 h after HFSF infection. RESULTS: Both specific and mutant probes banded precisely with HFSF nucleoprotein. The intensity value of the mutant probe was significantly lower than that of the specific probe (p < 0.05). HFSFs were successfully infected by the recombinant adenoviruses. The FLuc/RLuc fluorescence intensity ratio of Ad5f11p-pLAMA1SNPa-Luc2 (0.0238 +/- 0.0009) was significantly lower than that of Ad5f11p-pLAMA1SNPg-Luc2 (0.0281 +/- 0.0015) (p < 0.05). CONCLUSIONS: It is highly likely that SNP rs2089760 in the LAMA1 promoter region is located at the transcription factor binding site. The SNP rs2089760 G > A mutation reduces transcription factor binding ability and transcriptional initiation activity, and negatively regulates gene transcription of LAMA1. We suggest that LAMA1 SNP rs2089760 plays an important role in the development of PM. PMID- 26862818 TI - Delayed Graft Function in Living-Donor Kidney Transplant: A Middle Eastern Perspective. AB - With an increased incidence of living-donor kidney transplants, in response to increasing unmet needs for renal transplant, a clear understanding of determinants of posttransplant outcomes is essential. The importance of delayed graft function in deceased-donor kidney transplant is now part of conventional medical wisdom, due to the large amount of evidence focused on this aspect. However, the same is not true for living-donor kidney transplant, partly due to lack of evidence on this crucial clinical question and partly due to lack of awareness about this issue. The current review aims to highlight the importance of delayed graft function as a crucial determinant of outcomes in living-donor kidney transplant. An exhaustive search of online medical databases was performed with appropriate search criteria to collect evidence about delayed graft function after living-donor kidney transplant, with a special focus on studies from the Middle East. Data on incidence, impact, risk factors, and possible prevention modalities of delayed graft function in patients undergoing living-donor kidney transplant are presented. A key finding of this review is that contemporary incidence rates reported from the Middle East are comparatively higher than those reported from outside the region. Although in absolute terms the incidence is lower than deceased donor kidney transplant, the effects of delayed graft function on graft rejection and graft and patient survival are sufficiently large to warrant the formulation of specific treatment protocols. Key to formulating prevention and treatment strategies is identifying discrete risk factors for delayed graft function. Although this evidence is scant, an overview has been provided. Further studies examining different aspects of delayed graft function incidence after living-donor kidney transplant are urgently needed to address a so far little known clinical question. PMID- 26862817 TI - Bortezomib with dexamethasone as first-line treatment for AL amyloidosis with renal involvement. AB - Although bortezomib has reported efficacy in light chain (AL) amyloidosis, the role of bortezomib in combination with dexamethasone (BD) as the first-line treatment for patients with AL amyloidosis has not been determined. We analyzed the outcomes of 72 consecutive unselected patients, which received primary therapy with BD in a single center. The patients were newly diagnosed with AL amyloidosis with renal (100%), cardiac (72%), hepatic (19%) or nervous system (10%) involvement and underwent a median of 2 (1-6) cycles of BD treatment. A hematologic response was achieved in 75% of the patients within a median period of 2 months, and 45% of those patients achieved a complete response. A renal response was achieved in 50% and 60% of patients at 1 year and 2 years, respectively, and a cardiac response was achieved in 40% and 46% of patients at 1 year and 2 years, respectively. After a median follow-up period of 24 months, the median duration of progression free survival was 45 months, and the estimated overall survival rates at 12 and 24 months were 83% and 76%, respectively. Baseline Eastern Cooperative Oncology Group performance status and proteinuria were associated with overall survival. The BD regimen induced high rates of rapid hematologic and organ responses in AL amyloidosis patients. PMID- 26862819 TI - Humanized Monoclonal Antibody Alemtuzumab Treatment in Transplant. AB - Successful attenuation of allograft rejection rate is a major clinical aspect in transplant. The CD52 binding monoclonal antibody CAMPATH1 or alemtuzumab, in this aspect, shows a promise as an effective immunomodifier. This humanized monoclonal antibody efficiently depletes CD52-bearing mature B- and T lymphocytes from circulation and thereby causes transient lymphopenia, a condition for generalized immunosuppression. Alemtuzumab is an approved drug for the treatment of B cell chronic lymphocytic leukemia. However, its implication in transplant as nonsteroidal drug is a growing area of investigation. Here, we provided a brief account on alemtuzumab as an immunomodifier in allotransplant. PMID- 26862820 TI - Development of a Pig Model for Laparoscopic Kidney Transplant. AB - OBJECTIVES: Our aim was to describe a standardized laparoscopic kidney transplant procedure in a pig model. MATERIALS AND METHODS: Ten pigs underwent laparoscopic kidney autotransplant. A right-hand assisted nephrectomy was performed through a Pfannenstiel incision. After the graft was washed with Ringer lactate, it was transplanted into the right iliac vessels by pure laparoscopy. To maintain cold ischemia, a gauze-wrapped ice slush was placed below the allograft. The ureteroneocystostomy was performed through the Pfannenstiel incision. The contralateral ureter was ligated at the end of the procedure. After 24 hours, pigs were killed, and the allograft's perfusion function and presence of urine in the bladder were evaluated. RESULTS: Procedures for 2 animals (20%) could not be completed because of technical problems in the vascular anastomosis; the other 8 procedures (80%) were completed successfully. Seven allografts (87.5%) were functioning 24 hours after surgery, with urine in the bladder and good perfusion of the allograft. The other kidney presented with a venous thrombosis that was detected after death. Mean surgical times were 56.2 +/- 11.7 minutes for vein anastomosis and 44.7 +/- 23.1 minutes for artery anastomosis. Mean ischemia time was 193 minutes. Total duration of the procedure was clearly decreased in the last 4 animals undergoing transplant. CONCLUSIONS: Laparoscopic transplant is a difficult procedure that requires experience in kidney laparoscopy and laparoscopic vascular sutures. The experimental model presented is a good training option and can be used to evaluate different methods to maintain cold ischemia and to compare with the traditional open approach. PMID- 26862821 TI - Long-Term Follow-up After Right Laparoscopic Donor Nephrectomy and Inverted Kidney Transplant. AB - OBJECTIVES: The objective of this study was to investigate the long-term outcomes of inverted kidney transplant, an alternative easy and safe technique to overcome difficulties associated with short right renal vein anastomosis after laparoscopic donor nephrectomy. MATERIALS AND METHODS: Seventy-nine laparoscopic donor nephrectomies and intentionally inverted renal transplants were performed between 2004 and 2009. For these transplants, the renal artery was ligated by Hem o-lok (Weck Surgical Instruments, Teleflex Medical, Durham, NC, USA) and titanium clips, and the vein was closed with 2 Hem-o-lok clips, resulting in a short renal vein. By inverting the recovered kidney to the ipsilateral pelvic side of he recipient, the short renal vein is placed posterior and adjacent to the external iliac vein; this made an easy and safe short renal vein anastomosis possible. RESULTS: All donor nephrectomies were completed laparoscopically, and no conversion to open surgery was required. The mean warm and cold ischemic times were 7.3 minutes (range, 3.2-17.5 min) and 37.5 minutes (range, 14.2-88 min). Only 6 patients (7.6%) had delayed graft function. At 5 years after transplant, patients showed excellent graft function, with mean serum creatinine level of 1.46 mg/dL and graft survival of 93.7%. There were no occurrences of vascular thrombosis or acute rejection. However, 5 years after transplant, 4 patients had died, with 3 patients still having functional transplanted kidneys and 1 patient experiencing graft rejection 1 month before death. CONCLUSIONS: Inverted kidney transplant is an easy and safe method to overcome the complications associated with short right renal vein anastomosis after laparoscopic donor nephrectomy. This simple modification might obviate the need to elongate a short renal vein. PMID- 26862822 TI - Kidneys From Deceased Elderly Donors: Factors Associated With Adverse Outcomes. AB - OBJECTIVES: We evaluated risk factors that could adversely affect outcomes from elderly deceased-donor transplants. MATERIALS AND METHODS: In this single center retrospective study (112 patients), we studied the impact of acute rejection episodes, delayed graft function, donor-recipient age differences, HLA-DR mismatches, HLA antigen mismatches, recipient comorbidities, cold ischemia time, donor and recipient age, and donor serum creatinine level on short- and long-term graft survival. RESULTS: Mean ages of donors and recipients were 64.71 +/- 4.09 and 50.39 +/- 13.72 years. Delayed graft function was 40.2%, whereas acute rejection episode rate was 38%. Graft and patient survival rates were 80.4% and 67.7%, 63.6% and 91.9%, and 82.1% and 78.2% at 1, 3, and 5 years. Cold ischemia time, recipient comorbidity, and total HLA antigen mismatch did not significantly affect graft outcome. Acute rejection episode was an independent predictor of graft outcome (beta level = 2.857, t test = 2.3, P = .025). Donor age was a predictor of total graft survival duration (log-rank test gave chi-square test with 2 df = 12.292, P = .002). Donor estimated glomerular filtration rates >= 60 mL/min produced better outcomes than those < 60 mL/min (log-rank test gave chi squared test with 1 df = 7.213, P = .007). Multivariate Cox regression analysis showed that donor age and delayed graft function were not significant predictors of graft outcome (P > .05), whereas acute rejection episodes (hazard ratio 5.443; 95% confidence interval, 2.226-15.311; P < .001) and donor estimated glomerular filtration rate (hazard ratio 0.449; 95% confidence interval, 0.209-0.945; P = .035) remained significant predictors of cumulative graft survival. CONCLUSIONS: The risk factors mentioned above should be avoided to achieve better graft survival. Emphasis should not be on donor age alone. Good donor kidney function and proper immunosuppressive therapy to reduce acute rejection episodes are cornerstones to improved outcomes. PMID- 26862823 TI - Efficacy of Psychoeducational Intervention on Allograft Function in Kidney Transplant Patients: 10-Year Results of a Prospective Randomized Study. AB - OBJECTIVES: Improving treatment adherence to immunosuppressive agents could have positive effects on the morbidity and mortality of kidney transplant recipients. Our objective was to determine whether psychoeducational intervention aimed at improving treatment adherence also could improve 10-year kidney allograft survival rates. MATERIALS AND METHODS: A randomized open-label study compared a group who received psychoeducational intervention (n = 55) with a control group (n = 55), with all patients being kidney transplant recipients in the Department of Nephrology and Organ Transplantation (University Hospital, Toulouse, France). Psychoeducational intervention comprised 8 weekly sessions provided by multidisciplinary teams. Patients were included between 2002 and 2003. The primary endpoint was allograft survival at 10 years (ie, by 2012). A failed allograft or death with a functioning allograft was considered an event. RESULTS: Mean overall allograft survival rate at 10 years was 78.2% (95% confidence interval, 70.5-25.3). In the control group, 48 patients (43.6%) still had a functioning graft at 10 years versus 38 patients (34.5%) in the psychoeducational intervention group (P = .02). However, a log-rank test did not find any significant difference in allograft survival between the groups (P = .06). In multivariate analyses (Cox model), no factor was significantly associated with allograft survival at 10 years. CONCLUSIONS: After an initial 6-month observational adherence survey, there was no benefit to kidney allograft survival at 10 years after the psychoeducational intervention, which had aimed to improve patient adherence to treatment with immunosuppressive agents. This might be related to the fact that booster interventions are needed (eg, on a yearly basis). PMID- 26862824 TI - Stroke-Related Hospitalization and Mortality After a Kidney Allograft: A Population-Cohort Study. AB - OBJECTIVES: Stroke is a major cause of mortality in the general population but data regarding stroke-related hospitalization or mortality after a kidney transplant is limited. We determined risk for stroke-related episodes after a kidney transplant in a population-based cohort study of 19,103 kidney allograft recipients in England between 2001 and 2012. MATERIALS AND METHODS: The incidence of stroke-related events after a kidney transplant with pretransplant history of stroke, the incidence of stroke-related hospitalization or death among all kidney allograft recipients after a kidney transplant, and risk factors for stroke related mortality after a kidney transplant were examined. Data were obtained from hospital episode statistics (an administrative data warehouse that contains admissions to all National Health Service hospitals in England) and is linked to the Office for National Statistics, which collects information on all registered deaths in England. RESULTS: There were 782 nonfatal stroke-related hospitalizations and 113 stroke-related deaths (5.4% of total deaths) after a kidney transplant (median follow-up 4.4 y after a kidney transplant). Risk for all-cause mortality was higher for those recipients with, compared to those without, a history of stroke (21.5% vs 10.8%; P < .001). However, risk for stroke related mortality after a kidney transplant was no different. Kidney allograft recipients with nonfatal stroke episodes after a transplant were at a higher risk for all-cause and stroke-related mortality. In a Cox regression model, pretransplant history of stroke was an independent risk factor for all-cause mortality, but not stroke-related mortality, while posttransplant hospitalization with nonfatal stroke was a risk factor for both. CONCLUSIONS: Fatal and nonfatal stroke-related events are common among kidney allograft recipients. Further research is warranted to allow better risk stratification and facilitate clinical trials for risk attenuation of stroke after a kidney transplant. PMID- 26862825 TI - Long-Term Follow-Up of Active Treatment Versus Minimization of Immunosuppressive Agents in Patients With BK Virus-Associated Nephropathy After Kidney Transplant. AB - OBJECTIVES: There is no active treatment for postrenal transplant BK virus associated nephropathy proven to be effective so far. We assessed the effectiveness of actively treating this condition with combined leflunomide, intravenous immunoglobulin, and ciprofloxacin on long-term graft outcome compared with minimization of immunosuppressive drugs. MATERIALS AND METHODS: Kidney transplant recipients were screened for BK virus-associated nephropathy. Group 1 comprised 22 kidney trans plant recipients with twice-positive BK virus polymerase chain reaction results in urine and blood. After diagnosis was confirmed with graft biopsy, antimetabolite (mycophenolate mofetil or azathioprine) was changed to leflunomide and intravenous immunoglobulin and oral ciprofloxacin were given. Group 2 comprised 33 BK virus-associated nephropathy patients treated conventionally with reduced immunosuppressive medications. RESULTS: Fifty-five patients were treated (38 males [69%], 28 patients [50.9%] with type 2 diabetes mellitus). Mean HLA antigen mismatches were 3.65, and 28 patients (50.9%) were HLA-Cw7 negative. All patients received induction therapy, 30 patients (55.6%) received thymoglobulin, and 29 patients (52.7%) received antirejection therapy before BK virus-associated nephropathy diagnosis. Maintenance immunosuppression was prednisolone in 53 patients (96.3%), mycophenolate mofetil (2 g daily) in 52 patients (94.5%), and tacrolimus in 28 patients (50.9%). Subsequent rejection episodes occurred in 38% of patients after diagnosis. Basal mean estimated glomerular filtration rate was 52.5 +/- 25.5, which was reduced significantly to 38.1 +/- 27.8 mL/min/1.73 m(2) (P < .0001) at end of study but without significant differences between the groups (P = .08 and P = .17). Follow-up was 7.3 +/- 4.99 years. Although no significant differences were shown in patient outcome, graft survival was significantly better in group 2 (P = .032). CONCLUSIONS: Administration of 3 different anti-BK virus agents (leflunomide, intravenous immunoglobulin, ciprofloxacin) added no benefit to longterm outcome in patients with BK virus-associated nephropathy. Reduction of immunosuppressive medications appears to be a more effective treatment. PMID- 26862826 TI - Preservation of Endothelial and Smooth Muscle Function of Human Saphenous Vein Transplants. AB - OBJECTIVES: Methods for conservation and preservation of vascular grafts are often controversially discussed. Furthermore, immunologic monitoring or immunotherapy for allogeneic graft is not considered necessary in many cases. The present study was initiated to examine the cellular vitality and functional efficiency of vein transplant during preservation. MATERIALS AND METHODS: Twenty seven human vein segments (vena saphena magna) were stored after explant in University of Wisconsin solution or histidine-tryptophan-ketoglutarate solution at 4 degrees C. After 3, 24, 48, 72, and 96 hours, vein functionality was tested. Ring segments were fixed by triangles in Krebs-Henseleit buffer. Contractile function was measured after addition of potassium chloride solution (80 mM) and phenylephrine (0.2, 2, or 20 MUM). To investigate endothelium dependent vasorelaxation, 1 MUM acetylcholine was added. RESULTS: Of 27 segments, 5 showed endothelium-dependent relaxation. Vasorelaxation continued for up to 48 hours after administration of acetylcholine in University of Wisconsin solution and for up to 24 hours in histidine-tryptophane-ketoglutarate solution. At 48 hours, potassium chloride solution-induced vasocontraction was 17% more effective than phenylephrine in University of Wisconsin solution. University of Wisconsin solution was significantly more effective than histidine-tryptophane ketoglutarate solution in terms of preservation of phenylephrine (0.2, 2 MUM) induced vasocontraction. Phenylephrine (2 MUM)-induced contraction was retained in University of Wisconsin solution after 24 hours by 81% and after 48 hours by 55%, with comparable results in histidine-tryptophane-ketoglutarate solution of only 62% and 34% after 24 and 48 hours. CONCLUSIONS: At 48 hours, human saphenous vein transplants had better endothelium and smooth muscle function when preserved in University of Wisconsin solution versus histidine-tryptophane-ketoglutarate solution. PMID- 26862827 TI - Ascorbic Acid Supplementation During Ex Vivo Lung Perfusion. PMID- 26862828 TI - Psychiatric Manifestation of EAST Syndrome: Case Report and a Critical Assessment of Psychiatric Issues. PMID- 26862829 TI - Efficacy, Safety, and Tolerability of RBP-7000 Once-Monthly Risperidone for the Treatment of Acute Schizophrenia: An 8-Week, Randomized, Double-Blind, Placebo Controlled, Multicenter Phase 3 Study. AB - RBP-7000 is a sustained-release formulation of risperidone for the treatment of schizophrenia, designed to be administered by once-monthly subcutaneous injection using the ATRIGEL delivery system. This study assessed the efficacy, safety, and tolerability of RBP-7000 compared with placebo in subjects with acute exacerbation of schizophrenia. Inpatients were randomly assigned to 8 weeks of double-blind treatment with subcutaneous 90 or 120 mg of RBP-7000 or placebo. Efficacy was evaluated using a mixed-model repeated-measures analysis of the change from baseline (the last nonmissing value before the first dose of RBP-7000 or placebo on day 1) to end of the study in Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure) and Clinical Global Impression Severity score (secondary efficacy measure). The least-squares means from the repeated-measures analysis for the change from baseline in the PANSS total scores for placebo was -9.219 (SE, 1.2162). RBP-7000 produced statistically and clinically significant differences in mean reductions from baseline in PANSS total scores (90-mg RBP-7000 compared with placebo, -6.148 [-9.982 to -2.314], P = 0.0004; 120-mg RBP-7000 compared with placebo, -7.237 [-11.045 to -3.429], P < 0.0001) and significantly improved Clinical Global Impression-Severity scores (90 mg RBP-7000 compared with placebo, -0.350 [-0.557 to -0.143], P = 0.0002; 120-mg RBP-7000 compared with placebo, -0.396 [-0.602 to -0.190], P < 0.0001). Both RBP 7000 dosages were generally well tolerated. The most frequently reported treatment-emergent adverse events in RBP-7000 groups compared with placebo were somnolence, weight gain, and akathisia. The overall incidence of extrapyramidal syndrome-related effects was low and similar across groups. RBP-7000 may provide a new, long-acting alternative treatment for use in adults with acute schizophrenia. PMID- 26862830 TI - Development of a prediction model and estimation of cumulative risk for upper aerodigestive tract cancer on the basis of the aldehyde dehydrogenase 2 genotype and alcohol consumption in a Japanese population. AB - Alcohol consumption and the aldehyde dehydrogenase 2 (ALDH2) polymorphism are associated with the risk of upper aerodigestive tract cancer, and a significant gene-environment interaction between the two has been confirmed in a Japanese population. To aid the development of a personalized prevention strategy, we developed a risk-prediction model and estimated absolute risks stratified by a combination of the ALDH2 genotype and alcohol consumption. We carried out two age matched and sex-matched case-control studies: one (630 cases and 1260 controls) for model derivation and the second (654 cases and 654 controls) for external validation. On the basis of data from the derivation study, a prediction model was developed by fitting a conditional logistic regression model using the following predictors: age, sex, smoking, drinking, and the ALDH2 genotype. The risk model, including a combination of the ALDH2 genotype and alcohol consumption, provided high discriminatory accuracy and good calibration in both the derivation and the validation studies: C statistics were 0.82 (95% confidence interval 0.80-0.84) and 0.83 (95% confidence interval 0.81-0.85), respectively, and the calibration plots of both studies remained close to the ideal calibration line. Cumulative risks were obtained by combining odds ratios estimated from the risk model with the age-specific incidence rate and population size. For heavy drinkers with a heterozygous genotype, the cumulative risk at age 80 was above 20%. In contrast, risk in the other groups was less than 5%. In conclusion, modification of alcohol consumption according to the ALDH2 genotype will have a major impact on upper aerodigestive tract cancer prevention. These findings represent a simple and practical model for personalized cancer prevention. PMID- 26862831 TI - Screening colonoscopy volume and detection of colorectal neoplasms: a state-wide study from Bavaria, Germany. AB - Screening colonoscopy enables early detection of colorectal cancer and its precancerous lesions. The aim of this study was to assess the association of screening colonoscopy volume with colorectal neoplasm detection rate in routine practice. A registry-based study of individuals aged at least 55 years who underwent screening colonoscopy in Bavaria, Germany, between 2007 and 2009 was performed. Colorectal neoplasm detection rates (95% confidence intervals) were determined per physician. Physicians were grouped according to the number of screening colonoscopies performed per year (<50, 50-99, 100-199, >=200). A total of 203 363 individuals (median age 64 years, 55.2% women) underwent screening colonoscopy between 2007 and 2009. Colonoscopies were performed by 509 physicians. The detection rate of any neoplasm increased with screening colonoscopy volume from 21.9% among physicians conducting fewer than 50 screening colonoscopies per year to 27.5% among physicians conducting 200 or more screening colonoscopies per year (P-value for trend <0.0001). Increases in detection rates with colonoscopy volume were also observed for advanced neoplasms and for colorectal cancer (P-value for trend 0.16 and <0.0001, respectively). Differences were largest between physicians conducting fewer than 50 screening colonoscopies per year and other physicians. These results support a potential role of a minimum colonoscopy volume for high-quality colonoscopy screening. Differences in neoplasm detection rates were high between physicians conducting fewer than 50 screening colonoscopies per year and physicians with higher screening colonoscopy volume. PMID- 26862832 TI - The C9ORF72 expansion sizes in patients with psychosis: a population-based study on the Northern Finland Birth Cohort 1966. AB - Patients with behavioral variant frontotemporal dementia (bvFTD) have many psychotic symptoms, especially at the onset of the disease. The C9ORF72 expansion is the most common genetic etiology observed with bvFTD and the prevalence of the expansion is notably high among Finnish bvFTD patients. The aim of this study was to evaluate the prevalence of the C9ORF72 expansion among the clearly characterized patients with psychosis, mainly schizophrenia, in early midlife. The C9ORF72 repeat sizes were analyzed in 130 (48% women) patients with psychosis from the Northern Finland Birth Cohort 1966 (N=11,017), the mean onset age being 27.9 (SD 7.0) years. Despite the high frequency of psychiatric symptoms in bvFTD patients and the extremely high prevalence of the C9ORF72 expansion in Finland, pathogenic expansion (>40 repeats) was not detected among the Northern Finland Birth Cohort 1966 individuals with psychosis, indicating that these disorders, especially schizophrenia before the age of 43 years, may not be associated with the C9ORF72 expansion. However, we identified four cases with intermediate size repeats (17-26), but the role of the intermediate repeats in the etiology of psychosis is unknown. PMID- 26862833 TI - No association of GRIA1 polymorphisms with schizophrenia in the Chinese Han population. PMID- 26862834 TI - The Epidemiology of Concussions: Number and Nature of Concussions and Time to Recovery Among Female and Male Canadian Varsity Athletes 2008 to 2011. AB - OBJECTIVE: To provide incidence rates and days to symptom resolution and cognitive recovery stratified by sex and sport at a Canadian institution. STUDY DESIGN: A retrospective chart analysis. SUBJECTS: Seven hundred fifty-nine varsity level athletes competing in men's football, men's and women's soccer, men's and women's volleyball, men's and women's basketball, men's and women's ice hockey, women's field hockey, women's rugby, men's and women's tennis, men's and women's water polo, men's and women's swimming, badminton, cross-country, and track and field in the 2008 to 2009 season through the 2010 to 2011 season. MAIN OUTCOME MEASURES: Incidence of concussion, days to symptom recovery, and days to cognitive recovery as measured by clinical interpretation using the sports concussion assessment tool (SCAT)/SCAT2 and Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) with baseline and follow-up data. RESULTS: A total of 81 concussions were reported and diagnosed among 759 athletes. Significantly, more female athletes were concussed than male athletes (13.08%-7.53%, respectively; P = 0.014) with the highest rates in women's rugby [incidence density (ID) = 20.00 concussions per athlete-season], women's ice hockey (ID = 18.67 per athlete-season), and men's basketball (ID = 20.00 per athlete-season). Sex differences in symptom recovery and cognitive recovery were not significant. CONCLUSIONS: The incidence of concussion across multiple sports in a Canadian varsity athlete population is of concern. There are inconsistencies found between the time an athlete claims to have no symptoms and the time of neurocognitive recovery as measured by computerized neurocognitive testing. Therefore, objective computerized testing is recommended to ensure that athletes are functionally recovered before return to play. PMID- 26862835 TI - Evaluation of Lung Metastasis in Mouse Mammary Tumor Models by Quantitative Real time PCR. AB - Metastatic disease is the spread of malignant tumor cells from the primary cancer site to a distant organ and is the primary cause of cancer associated death. Common sites of metastatic spread include lung, lymph node, brain, and bone. Mechanisms that drive metastasis are intense areas of cancer research. Consequently, effective assays to measure metastatic burden in distant sites of metastasis are instrumental for cancer research. Evaluation of lung metastases in mammary tumor models is generally performed by gross qualitative observation of lung tissue following dissection. Quantitative methods of evaluating metastasis are currently limited to ex vivo and in vivo imaging based techniques that require user defined parameters. Many of these techniques are at the whole organism level rather than the cellular level. Although newer imaging methods utilizing multi-photon microscopy are able to evaluate metastasis at the cellular level, these highly elegant procedures are more suited to evaluating mechanisms of dissemination rather than quantitative assessment of metastatic burden. Here, a simple in vitro method to quantitatively assess metastasis is presented. Using quantitative Real-time PCR (QRT-PCR), tumor cell specific mRNA can be detected within the mouse lung tissue. PMID- 26862836 TI - Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes. AB - Enzyme catalysis evolved in an aqueous environment. The influence of solvent dynamics on catalysis is, however, currently poorly understood and usually neglected. The study of water dynamics in enzymes and the associated thermodynamical consequences is highly complex and has involved computer simulations, nuclear magnetic resonance (NMR) experiments, and calorimetry. Water tunnels that connect the active site with the surrounding solvent are key to solvent displacement and dynamics. The protocol herein allows for the engineering of these motifs for water transport, which affects specificity, activity and thermodynamics. By providing a biophysical framework founded on theory and experiments, the method presented herein can be used by researchers without previous expertise in computer modeling or biophysical chemistry. The method will advance our understanding of enzyme catalysis on the molecular level by measuring the enthalpic and entropic changes associated with catalysis by enzyme variants with obstructed water tunnels. The protocol can be used for the study of membrane bound enzymes and other complex systems. This will enhance our understanding of the importance of solvent reorganization in catalysis as well as provide new catalytic strategies in protein design and engineering. PMID- 26862838 TI - A Diversity and Inclusion Framework for Medical Education. PMID- 26862837 TI - Lateral Root Inducible System in Arabidopsis and Maize. AB - Lateral root development contributes significantly to the root system, and hence is crucial for plant growth. The study of lateral root initiation is however tedious, because it occurs only in a few cells inside the root and in an unpredictable manner. To circumvent this problem, a Lateral Root Inducible System (LRIS) has been developed. By treating seedlings consecutively with an auxin transport inhibitor and a synthetic auxin, highly controlled lateral root initiation occurs synchronously in the primary root, allowing abundant sampling of a desired developmental stage. The LRIS has first been developed for Arabidopsis thaliana, but can be applied to other plants as well. Accordingly, it has been adapted for use in maize (Zea mays). A detailed overview of the different steps of the LRIS in both plants is given. The combination of this system with comparative transcriptomics made it possible to identify functional homologs of Arabidopsis lateral root initiation genes in other species as illustrated here for the CYCLIN B1;1 (CYCB1;1) cell cycle gene in maize. Finally, the principles that need to be taken into account when an LRIS is developed for other plant species are discussed. PMID- 26862839 TI - Applying Weiss's Theory of Change to the Evaluation of Premedical Programs. PMID- 26862840 TI - Characteristics of Early Recipients of Patient-Centered Outcomes Research Institute Funding. AB - The Patient Protection and Affordable Care Act (ACA) is grounded in the goals of increasing access, improving quality, and reducing cost in the U.S. health care system. The ACA established the Patient-Centered Outcomes Research Institute (PCORI) to help accomplish these goals through patient-focused research. PCORI has a different charge than its federally supported counterpart, the National Institutes of Health (NIH)-to fund research that ultimately helps patients make better-informed health care decisions. The authors examined characteristics of the recipients and settings of the first six rounds of PCORI funding and differentiated PCORI and NIH funding patterns to analyze the extent to which PCORI is accomplishing the goals set out by the ACA. The authors performed a retrospective review of publicly available datasets, supplemented by a short questionnaire to funded PCORI principal investigators (PIs). The authors analyzed PCORI's first six funding cycles (2011-2014) and data on NIH funding patterns (2000-2013) to determine whether PCORI and NIH funding patterns differed by investigator, department, and institution, and whether PCORI had funded research in primary care settings. The authors found that PCORI is funding a more diverse cadre of PIs and biomedical departments than is NIH, but not a greater diversity of institutions, and that less than one-third of PCORI studies involve or are relevant to primary care--the largest patient care platform in the United States. As PCORI looks to be refunded, it is important that research funding is further evaluated and publicly acknowledged to assess whether goals are being achieved. PMID- 26862841 TI - The Mock Academic Faculty Position Competition: A Pilot Professional and Career Development Opportunity for Postdoctoral Fellows. AB - PROBLEM: Medical educators face a dilemma in countries like Canada, where policy makers and strategic planners have prioritized highly qualified personnel and expanded recruitment of advanced trainees at a time when early-career specialists face prolonged job insecurity as they transition to professional employment. The University of Calgary Cumming School of Medicine hatched the Mock Academic Faculty Position competition to test the school's existing capacity to address the pressing career development needs of highly trained graduates. APPROACH: The competition was piloted in May-June 2014. Approximately 180 postdoctoral fellows were invited to compete; 34 submitted portfolios. The Postdoctoral Program Office established a longlist of 12 applicants. Through reviews, a selection committee identified 3 finalists to participate in a daylong event consisting of a research presentation and committee interview. The event was followed by approximately 70 audience members at any given time who were invited to complete anonymous evaluation forms and/or exit interviews. OUTCOMES: The selection committee deduced a vast majority of applicants did not sell their skills effectively or demonstrate research programs independent from supervisors. Exit interviews conducted with 40 audience members indicated 36 (90%) picked the same finalist as the selection committee, 34 (85%) found the process "nerve racking," and 28 (70%) had no previous idea of what goes on inside an academic committee interview. NEXT STEPS: A key recommendation for future iterations is early attention to systematizing feedback to ensure more direct impact for nonfinalists. Alternative initiatives for those gearing up for industry or public-sector work are being prepared. PMID- 26862842 TI - Primary Care Research in the Patient-Centered Outcomes Research Institute's Portfolio. AB - In their article in this issue, Mazur and colleagues analyze the characteristics of early recipients of funding from the Patient-Centered Outcomes Research Institute (PCORI). Mazur and colleagues note correctly that PCORI has a unique purpose and mission and suggest that it should therefore have a distinct portfolio of researchers and departments when compared with other funders such as the National Institutes of Health (NIH). Responding on behalf of PCORI, the authors of this Commentary agree with the characterization of PCORI's mission as distinct from that of NIH and others. They agree too that data found on PCORI's Web site demonstrate that PCORI's portfolio of researchers and departments is more diverse and more heavily populated with clinician researchers, as would be expected. The authors take issue with Mazur and colleagues' suggestion that because half of clinical visits occur within primary care settings, half of PCORI's funded research should be based in primary care departments. PCORI's portfolio reflects what patients and others tell PCORI are the critical questions. Many of these do, in fact, occur with more complex conditions in specialty care. The authors question whether the research of primary care departments is too narrowly focused and whether it sufficiently considers study of these complex conditions. Research on more complex conditions including heart failure, coronary artery disease, and multiple comorbid conditions could be highly valuable when approached from the primary care perspective, where many of the comparative effectiveness questions first arise. PMID- 26862843 TI - A Fabrication Method for Highly Stretchable Conductors with Silver Nanowires. AB - Stretchable electronics are identified as a key technology for electronic applications in the next generation. One of the challenges in fabrication of stretchable electronic devices is the preparation of stretchable conductors with great mechanical stability. In this study, we developed a simple fabrication method to chemically solder the contact points between silver nanowire (AgNW) networks. AgNW nanomesh was first deposited on a glass slide via spray coating method. A reactive ink composed of silver nanoparticle (AgNPs) precursors was applied over the spray coated AgNW thin films. After heating for 40 min, AgNPs were preferentially generated over the nanowire junctions to solder the AgNW nanomesh, and reinforced the conducting network. The chemically modified AgNW thin film was then transferred to polyurethane (PU) substrates by casting method. The soldered AgNW thin films on PU exhibited no obvious change in electrical conductivity under stretching or rolling process with elongation strains up to 120%. PMID- 26862844 TI - Removal of foreign bodies in the upper gastrointestinal tract in adults: European Society of Gastrointestinal Endoscopy (ESGE) Clinical Guideline. AB - This Guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE). It addresses the removal of foreign bodies in the upper gastrointestinal tract in adults. Recommendations Nonendoscopic measures 1 ESGE recommends diagnostic evaluation based on the patient's history and symptoms. ESGE recommends a physical examination focused on the patient's general condition and to assess signs of any complications (strong recommendation, low quality evidence). 2 ESGE does not recommend radiological evaluation for patients with nonbony food bolus impaction without complications. We recommend plain radiography to assess the presence, location, size, configuration, and number of ingested foreign bodies if ingestion of radiopaque objects is suspected or type of object is unknown (strong recommendation, low quality evidence). 3 ESGE recommends computed tomography (CT) scan in all patients with suspected perforation or other complication that may require surgery (strong recommendation, low quality evidence). 4 ESGE does not recommend barium swallow, because of the risk of aspiration and worsening of the endoscopic visualization (strong recommendation, low quality evidence). 5 ESGE recommends clinical observation without the need for endoscopic removal for management of asymptomatic patients with ingestion of blunt and small objects (except batteries and magnets). If feasible, outpatient management is appropriate (strong recommendation, low quality evidence). 6 ESGE recommends close observation in asymptomatic individuals who have concealed packets of drugs by swallowing ("body packing"). We recommend against endoscopic retrieval. We recommend surgical referral in cases of suspected packet rupture, failure of packets to progress, or intestinal obstruction (strong recommendation, low quality evidence). Endoscopic measures 7 ESGE recommends emergent (preferably within 2 hours, but at the latest within 6 hours) therapeutic esophagogastroduodenoscopy for foreign bodies inducing complete esophageal obstruction, and for sharp-pointed objects or batteries in the esophagus. We recommend urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for other esophageal foreign bodies without complete obstruction (strong recommendation, low quality evidence). 8 ESGE suggests treatment of food bolus impaction in the esophagus by gently pushing the bolus into the stomach. If this procedure is not successful, retrieval should be considered (weak recommendation, low quality evidence). The effectiveness of medical treatment of esophageal food bolus impaction is debated. It is therefore recommended, that medical treatment should not delay endoscopy (strong recommendation, low quality evidence). 9 In cases of food bolus impaction, ESGE recommends a diagnostic work-up for potential underlying disease, including histological evaluation, in addition to therapeutic endoscopy (strong recommendation, low quality evidence). 10 ESGE recommends urgent (within 24 hours) therapeutic esophagogastroduodenoscopy for foreign bodies in the stomach such as sharp-pointed objects, magnets, batteries and large/long objects. We suggest nonurgent (within 72 hours) therapeutic esophagogastroduodenoscopy for medium-sized blunt foreign bodies in the stomach (strong recommendation, low quality evidence). 11 ESGE recommends the use of a protective device in order to avoid esophagogastric/pharyngeal damage and aspiration during endoscopic extraction of sharp-pointed foreign bodies. Endotracheal intubation should be considered in the case of high risk of aspiration (strong recommendation, low quality evidence). 12 ESGE suggests the use of suitable extraction devices according to the type and location of the ingested foreign body (weak recommendation, low quality evidence). 13 After successful and uncomplicated endoscopic removal of ingested foreign bodies, ESGE suggests that the patient may be discharged. If foreign bodies are not or cannot be removed, a case-by-case approach depending on the size and type of the foreign body is suggested (weak recommendation, low quality evidence). PMID- 26862845 TI - Influence of reviewers' clinical backgrounds on interpretation of confocal laser endomicroscopy findings. AB - BACKGROUND AND STUDY AIMS: Substantial differences in endoscopic strategy for gastric cancer exist between Western and Eastern countries, owing to clinicoepidemiological diversity, including differences in the prevalence of gastric cancer. This international multicenter study involved German and Japanese institutions and aimed to evaluate the influence of reviewers' clinical backgrounds on interpreting probe-based confocal laser endomicroscopy (pCLE) findings for diagnosis of superficial gastric lesions. PATIENTS AND METHODS: 39 reviewers answered questionnaires about their clinical background and then reviewed 30 sets of white light endoscopy (WLE) and pCLE video clips via an online questionnaire. For each set of clips, reviewers were asked to classify lesions as neoplastic or non-neoplastic. RESULTS of video reviews were compared with the final histopathological diagnosis for each lesion. The accuracy of diagnosis based on WLE + pCLE was compared with that based on WLE alone for each aspect of clinical background. RESULTS: The overall accuracy of diagnosis based on WLE + pCLE was higher than that based on WLE alone (73.93 % vs. 65.64 %, P = .0002). Outcomes of expert gastroenterologists were better than those of pathologists (P = .038 for WLE, P = .002 for WLE + pCLE) and outcomes of reviewers at Japanese institutions were better than those of reviewers at German institutions (P = .001 for WLE, P < .001 for WLE + pCLE). CONCLUSIONS: Reviewers from Japanese institutions and expert gastroenterologists performed well in the pCLE interpretation. Substantial experience in conventional endoscopy is important for interpreting pCLE images for the diagnosis of gastric cancer.University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR; www.umin.ac.jp/ctr/index.htm) number UMIN 000013437). PMID- 26862846 TI - Distinct lymphocyte antigens 6 (Ly6) family members Ly6D, Ly6E, Ly6K and Ly6H drive tumorigenesis and clinical outcome. AB - Stem cell antigen-1 (Sca-1) is used to isolate and characterize tumor initiating cell populations from tumors of various murine models [1]. Sca-1 induced disruption of TGF-beta signaling is required in vivo tumorigenesis in breast cancer models [2, 3-5]. The role of human Ly6 gene family is only beginning to be appreciated in recent literature [6-9]. To study the significance of Ly6 gene family members, we have visualized one hundred thirty gene expression omnibus (GEO) dataset using Oncomine (Invitrogen) and Georgetown Database of Cancer (G DOC). This analysis showed that four different members Ly6D, Ly6E, Ly6H or Ly6K have increased gene expressed in bladder, brain and CNS, breast, colorectal, cervical, ovarian, lung, head and neck, pancreatic and prostate cancer than their normal counter part tissues. Increased expression of Ly6D, Ly6E, Ly6H or Ly6K was observed in sub-set of cancer type. The increased expression of Ly6D, Ly6E, Ly6H and Ly6K was found to be associated with poor outcome in ovarian, colorectal, gastric, breast, lung, bladder or brain and CNS as observed by KM plotter and PROGgeneV2 platform. The remarkable findings of increased expression of Ly6 family members and its positive correlation with poor outcome on patient survival in multiple cancer type indicate that Ly6 family members Ly6D, Ly6E, Ly6K and Ly6H will be an important targets in clinical practice as marker of poor prognosis and for developing novel therapeutics in multiple cancer type. PMID- 26862847 TI - Clinical response to azacitidine therapy depends on microRNA-29c (miR-29c) expression in older acute myeloid leukemia (AML) patients. AB - Acute myeloid leukemia (AML) is a heterogeneous disease with different clinical course and prognosis. microRNA-29 (miR-29) family of non-coding small RNAs can play an important role in pathogenesis of AML, but also can influence response to therapy.The purpose of the study was to evaluate miR-29c expression in AML patients in relationship to clinical parameters and response to chemotherapy, including azacitidine. MATERIALS AND METHODS: miR-29c expression has been analyzed using RT-PCR in 95 bone marrow specimens from newly diagnosed AML patients in comparison to 20 healthy subject. RESULTS: We showed up-regulated miR 29c expression in AML patients which was linked also to higher risk of disease relapse after achieving complete remission. In subset of elderly AML patients treated with azacitidine, low miR-29c expression at diagnosis correlated with good response to therapy. CONCLUSIONS: miR-29c is of prognostic value and influences response to azacitidine treatment in older AML patients. PMID- 26862849 TI - Frequency of CD4+CD25+Foxp3+ cells in peripheral blood in relation to urinary bladder cancer malignancy indicators before and after surgical removal. AB - Tumor cells communicate with stromal cells, including cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs), to form microenvironment inhibiting immune responses. Regulatory T cells (Tregs, CD4+CD25+FoxP3+) stimulate immune tolerance and facilitate tumor progression. We analyzed the changes in Treg frequencies assessed using flow cytometry in the peripheral blood of patients with urothelial bladder cancer before and after tumor-removal. Changes in Treg frequency were investigated in relation to clinicopathomorphological indicators of tumor malignancy and expression of RCAS1 on CAFs and TAMs. Higher Treg frequencies were observed in early phase of tumor growth (pTa-pT2), in larger tumors, with more aggressive type of invasion, and with expression of RCAS1. The later phase of tumor development, accompanied by a nonclassic differentiations and pT3-pT4 advancement, had lower number of tumor infiltrating lymphocytes (TILs) and lower Treg frequency. Furthermore, in pT2-pT4 tumors, a decreased post-surgery Treg frequency was associated with poorer prognosis: patients with the lowest frequency of Tregs died first. These findings strongly suggest that the Treg frequencies at later phase of tumor growth, associated with a low anti-tumor response, represent a new and important prognostic indicator in urinary bladder cancer. PMID- 26862848 TI - Phospholipid profiling identifies acyl chain elongation as a ubiquitous trait and potential target for the treatment of lung squamous cell carcinoma. AB - Lung cancer is the leading cause of cancer death. Beyond first line treatment, few therapeutic options are available, particularly for squamous cell carcinoma (SCC). Here, we have explored the phospholipidomes of 30 human SCCs and found that they almost invariably (in 96.7% of cases) contain phospholipids with longer acyl chains compared to matched normal tissues. This trait was confirmed using in situ 2D-imaging MS on tissue sections and by phospholipidomics of tumor and normal lung tissue of the L-IkkalphaKA/KA mouse model of lung SCC. In both human and mouse, the increase in acyl chain length in cancer tissue was accompanied by significant changes in the expression of acyl chain elongases (ELOVLs). Functional screening of differentially expressed ELOVLs by selective gene knockdown in SCC cell lines followed by phospholipidomics revealed ELOVL6 as the main elongation enzyme responsible for acyl chain elongation in cancer cells. Interestingly, inhibition of ELOVL6 drastically reduced colony formation of multiple SCC cell lines in vitro and significantly attenuated their growth as xenografts in vivo in mouse models. These findings identify acyl chain elongation as one of the most common traits of lung SCC discovered so far and pinpoint ELOVL6 as a novel potential target for cancer intervention. PMID- 26862850 TI - Reduced RKIP enhances nasopharyngeal carcinoma radioresistance by increasing ERK and AKT activity. AB - Raf kinase inhibitory protein (RKIP) functions as a chemo-immunotherapeutic sensitizer of cancers, but regulation of RKIP on tumor radiosensitivity remains largely unexplored. In this study, we investigate the role and mechanism of RKIP in nasopharyngeal carcinoma (NPC) radioresistance. The results showed that RKIP was frequently downregulated in the radioresistant NPC tissues compared with radiosensitive NPC tissues, and its reduction correlated with NPC radioresistance and poor patient survival, and was an independent prognostic factor. In vitro radioresponse assay showed that RKIP overexpression decreased while RKIP knockdown increased NPC cell radioresistance. In the NPC xenografts, RKIP overexpression decreased while RKIP knockdown increased tumor radioresistance. Mechanistically, RKIP reduction promoted NPC cell radioresistance by increasing ERK and AKT activity, and AKT may be a downstream transducer of ERK signaling. Moreover, the levels of phospho-ERK-1/2 and phospho-AKT were increased in the radioresistant NPC tissues compared with radiosensitive ones, and negatively associated with RKIP expression, indicating that RKIP-regulated NPC radioresponse is mediated by ERK and AKT signaling in the clinical samples. Our data demonstrate that RKIP is a critical determinant of NPC radioresponse, and its reduction enhances NPC radioresistance through increasing ERK and AKT signaling activity, highlighting the therapeutic potential of RKIP-ERK-AKT signaling axis in NPC radiosensitization. PMID- 26862851 TI - Brachyury identifies a class of enteroendocrine cells in normal human intestinal crypts and colorectal cancer. AB - Normal homeostasis of adult intestinal epithelium and repair following tissue damage is maintained by a balance of stem and differentiated cells, many of which are still only poorly characterised. Enteroendocrine cells of the gut are a small population of differentiated, secretory cells that are critical for integrating nutrient sensing with metabolic responses, dispersed amongst other epithelial cells. Recent evidence suggests that sub-sets of secretory enteroendocrine cells can act as reserve stem cells. Given the link between cells with stem-like properties and cancer, it is important that we identify factors that might provide a bridge between the two. Here, we identify a sub-set of chromogranin A positive enteroendocrine cells that are positive for the developmental and cancer associated transcription factor Brachyury in normal human small intestinal and colonic crypts. Whilst chromogranin A-positive enteroendocrine cells are also Brachyury-positive in colorectal tumours, expression of Brachyury becomes more diffuse in these samples, suggesting a more widespread function in cancer. The finding of the developmental transcription factor Brachyury in normal adult human intestinal crypts may extend the functional complexity of enteroendocrine cells and serves as a platform for assessment of the molecular processes of intestinal homeostasis that underpins our understanding of human health, cancer and aging. PMID- 26862852 TI - Non-coding RNA LINC00857 is predictive of poor patient survival and promotes tumor progression via cell cycle regulation in lung cancer. AB - We employed next generation RNA sequencing analysis to reveal dysregulated long non-coding RNAs (lncRNAs) in lung cancer utilizing 461 lung adenocarcinomas (LUAD) and 156 normal lung tissues from 3 separate institutions. We identified 281 lncRNAs with significant differential-expression between LUAD and normal lung tissue. LINC00857, a top deregulated lncRNAs, was overexpressed in tumors and significantly associated with poor survival in LUAD. knockdown of LINC00857 with siRNAs decreased tumor cell proliferation, colony formation, migration and invasion in vitro, as well as tumor growth in vivo. Overexpression of LINC00857 increased cancer cell proliferation, colony formation and invasion. Mechanistic analyses indicated that LINC00857 mediates tumor progression via cell cycle regulation. Our study highlights the diagnostic/prognostic potential of LINC00857 in LUAD besides delineating the functional and mechanistic aspects of its aberrant disease specific expression and potentially using as a new therapeutic target. PMID- 26862854 TI - Meta-analysis of the association between selenium and gastric cancer risk. AB - To clarify the effects of selenium level on the risk of gastric cancer (GC) and GC mortality, a meta-analysis was performed. Related studies were identified from PubMed, EMBASE, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM). Pooled ORs and 95% CIs were used to assess the strengthof the associations. A total of 8 studies including 17834 subjects were involved in this meta-analysis. High selenium level was associated with GC risk in case-control study (OR = 0.62, 95% CI 0.44-0.89, P = 0.009; I2 = 52%) and cohort study (OR = 0.87, 95% CI 0.78-0.97, P = 0.01; I2 = 25%). In addition, high selenium level was associated with GC mortality risk (OR = 0.90, 95% CI 0.84-0.97, P = 0.006, I2 = 49%). In summary, this meta-analysis suggested that selenium might inversely associated with GC risk and GC mortality. PMID- 26862853 TI - Defining specificity and on-target activity of BH3-mimetics using engineered B ALL cell lines. AB - One of the hallmarks of cancer is a resistance to the induction of programmed cell death that is mediated by selection of cells with elevated expression of anti-apoptotic members of the BCL-2 family. To counter this resistance, new therapeutic agents known as BH3-mimetic small molecules are in development with the goal of antagonizing the function of anti-apoptotic molecules and promoting the induction of apoptosis. To facilitate the testing and modeling of BH3-mimetic agents, we have developed a powerful system for evaluation and screening of agents both in culture and in immune competent animal models by engineering mouse leukemic cells and re-programming them to be dependent on exogenously expressed human anti-apoptotic BCL-2 family members. Here we demonstrate that this panel of cell lines can determine the specificity of BH3-mimetics to individual anti apoptotic BCL-2 family members (BCL-2, BCL-XL, BCL-W, BFL-1, and MCL-1), demonstrate whether cell death is due to the induction of apoptosis (BAX and BAK dependent), and faithfully assess the efficacy of BH3-mimetic small molecules in pre-clinical mouse models. These cells represent a robust and valuable pre clinical screening tool for validating the efficacy, selectivity, and on-target action of BH3-mimetic agents. PMID- 26862855 TI - Expression of the bitter receptor T2R38 in pancreatic cancer: localization in lipid droplets and activation by a bacteria-derived quorum-sensing molecule. AB - T2R38 belongs to the family of bitter receptors and was initially detected in cells of the oral cavity. We now describe expression of T2R38 in tumor cells in patients with pancreatic cancer and in tumor-derived cell lines. T2R38 is localized predominantly intracellular in association with lipid droplets, particularly with the lipid droplet membrane. The receptor can be activated by the bona fide ligand for T2R38, phenylthiourea (PTU), and by N-acetyl-dodecanoyl homoserine (AHL-12), a quorum sensing molecule of Pseudomonas aeruginosa, the latter is the only known natural ligand for T2R38. In response to PTU or AHL-12, key transcription factors are activated including phosphorylation of the MAP kinases p38 and ERK1/2, and upregulation of NFATc1. Moreover, we found increased expression of the multi-drug resistance protein 1 (also known as ABCB1), a transmembrane transporter molecule, participating in shuttling of a plethora of drugs, such as chemotherapeutics or antibiotics. In conclusion, our data indicate a new, additional function of the taste receptor T2R38 beyond sensing "bitter". Moreover, because T2R38 can be stimulated by a bacteria-derived signaling molecule the receptor could link microbiota and cancer. PMID- 26862856 TI - Androgens downregulate miR-21 expression in breast cancer cells underlining the protective role of androgen receptor. AB - Although the protective role of androgen receptor (AR) in breast cancer (BC) is well established, the mechanisms involved remains largely unexplored. MicroRNAs play fundamental roles in many biological processes, including tumor cell development and metastasis. Herein, we report that androgens reduce BC cells proliferation acting as a negative modulator of the onco-miRNA-21.The synthetic androgen miboleron (Mib) decreases BC cell proliferation induced by miR-21 over expression and AR knockdown evidenced the requirement of AR in the down regulation of miR-21 expression. These effects seem to be a general mechanism occurring in BC tissues.Chromatin immune-precipitation (ChIP) analysis disclosed the binding of AR to a specific ARE sequence in miR-21 proximal promoter and recognizes the recruitment of HDAC3 as component for AR-mediated transcriptional repression. Such event is associated to a significantly reduced PolII binding in Mib treated extracts confirming that activated AR is a transcriptional repressor of miR-21 expression, providing further insight into the protective role of androgens in breast cancer cells.Collectively, our data and the widespread AR expression in primary and metastatic breast tumours, suggest a careful examination of the therapeutic potential of androgens also in potentiating the effectiveness of anti-oestrogen adjuvant therapies. PMID- 26862858 TI - The application of a multi-dimensional assessment approach to talent identification in Australian football. AB - This study investigated whether a multi-dimensional assessment could assist with talent identification in junior Australian football (AF). Participants were recruited from an elite under 18 (U18) AF competition and classified into two groups; talent identified (State U18 Academy representatives; n = 42; 17.6 +/- 0.4 y) and non-talent identified (non-State U18 Academy representatives; n = 42; 17.4 +/- 0.5 y). Both groups completed a multi-dimensional assessment, which consisted of physical (standing height, dynamic vertical jump height and 20 m multistage fitness test), technical (kicking and handballing tests) and perceptual-cognitive (video decision-making task) performance outcome tests. A multivariate analysis of variance tested the main effect of status on the test criterions, whilst a receiver operating characteristic curve assessed the discrimination provided from the full assessment. The talent identified players outperformed their non-talent identified peers in each test (P < 0.05). The receiver operating characteristic curve reflected near perfect discrimination (AUC = 95.4%), correctly classifying 95% and 86% of the talent identified and non talent identified participants, respectively. When compared to single assessment approaches, this multi-dimensional assessment reflects a more comprehensive means of talent identification in AF. This study further highlights the importance of assessing multi-dimensional performance qualities when identifying talented team sports. PMID- 26862859 TI - Absorption intensity changes and frequency shifts of fundamental and first overtone bands for OH stretching vibration of methanol upon methanol-pyridine complex formation in CCl4: analysis by NIR/IR spectroscopy and DFT calculations. AB - Infrared (IR) and near infrared (NIR) spectra were measured for methanol and the methanol-pyridine complex in carbon tetrachloride. Upon the formation of the methanol-pyridine complex, the frequencies of both the fundamental and first overtone bands of the OH stretching vibration shifted to lower frequencies, and the absorption intensity of the fundamental increased significantly, while that of the first overtone decreased markedly. By using quantum chemical calculations, we estimated the absorption intensities and frequencies of the fundamental and first overtone bands for the OH stretching vibration based on the one-dimensional Schrodinger equation. The calculated results well reproduced the experimental results. The molecular vibration potentials and dipole moment functions of the OH stretching vibration modes were compared between methanol and the methanol pyridine complex in terms of absorption intensity changes and frequency shifts. The large change in the dipole moment function was found to be the main cause for the variations in absorption intensity for the fundamental and first overtone bands. PMID- 26862857 TI - miR-21 expression and clinical outcome in locally advanced pancreatic cancer: exploratory analysis of the pancreatic cancer Erbitux, radiotherapy and UFT (PERU) trial. AB - BACKGROUND: Locally advanced pancreatic cancer (LAPC) is associated with high mortality, and biomarker-driven treatment approach is currently lacking. This study evaluated safety and efficacy of a combination approach of chemotherapy followed by chemo-radiotherapy (CRT) +/- cetuximab, and the prognostic role of miR-21 in patients with LAPC treated with a multimodality approach. PATIENTS AND METHODS: This was a randomised phase II trial in which patients with inoperable LAPC were offered gemcitabine and capecitabine (GEM-CAP) for 16 weeks. Patients with stable disease or response after GEM-CAP were randomised to capecitabine or UFT plus radiotherapy (RT) (A), or capecitabine or UFT plus cetuximab plus RT (B). The primary outcome of the study was overall survival (OS). Clinical outcome was compared according to baseline circulating miR-21 levels. RESULTS: 17 patients were enrolled and treated with GEM-CAP, with 13 patients achieving disease control and being randomised to arms A (n:7) and B (n:6). After a median follow-up of 61.2 months, median progression free survival (PFS) was 10.4 months and 12.7 months, median OS was 15.8 months and 22.0 months in arms A and B respectively (p > 0.05). Patients with high baseline plasma miR-21 had worse PFS (3.5 vs. 12.7 months; p:0.032) and OS (5.1 vs 15.3 months; p:0.5) compared to patients with low miR-21. Circulating miR-21 levels reflected miR-21 expression within the tissues. CONCLUSIONS: Addition of Cetuximab to CRT following induction chemotherapy did not improve survival. High miR-21 baseline plasma expression was associated with poor clinical outcome in LAPC patients treated with induction chemotherapy followed by chemo-radiotherapy. PMID- 26862862 TI - The mechanism of excited state proton dissociation in microhydrated hydroxylamine clusters. AB - The dynamics and mechanism of excited-state proton dissociation and transfer in microhydrated hydroxylamine clusters are studied using NH2OH(H2O)n (n = 1-4) as model systems and the DFT/B3LYP/aug-cc-pVDZ and TD-DFT/B3LYP/aug-cc-pVDZ methods as model calculations. This investigation is based on the Forster acidity scheme and emphasizes the photoacid dissociation in the ground (S0) and lowest singlet excited states (S1) and the interplay between the photo and thermal excitations. The quantum chemical results suggest that the intermediate complexes are formed only in the S1 state in a low local-dielectric environment (e.g., epsilon = 1) and that upon the S0-> S1 transition, the photon energy excites mostly NH2OH, which leads to a homolytic cleavage of the O-H bond and to dynamically stable charge-separated Rydberg-like H-bond complexes (e.g., NH2O-H3O(+)). The potential energy surfaces for proton displacement in the smallest Rydberg-like H-bond complex support the intersection of the S0 and S1 states in low local-dielectric environments, whereas in a high local-dielectric environment (e.g., epsilon = 78), these two states are completely separated. Based on the static results, a photoacid-dissociation mechanism that involves Rydberg-like H-bond complex formation, an H-bond chain extension and fluctuations in the local-dielectric environment is proposed. NVT-BOMD simulations confirm the static results and show that the dynamic behavior of the dissociating proton in the S1 state is not different from that of the protonated H-bond systems in the ground state, which consists of the oscillatory shuttling and structural diffusion motions. These findings allow our theoretical methods, which have been used successfully in protonated H-bond systems in the ground state, to be applied in the study of the photoacid-dissociation processes. The current theoretical study suggests effective steps as well as guidelines for the investigation of the dynamics of the photoacid-dissociation and transfer processes in the Forster acidity scheme, provided that the exciting photon does not lead to a significant change in the structure of the intermediate complex in the excited state. PMID- 26862863 TI - Controlled synthesis of mixed-valent Fe-containing metal organic frameworks for the degradation of phenol under mild conditions. AB - A series of MIL-53(Fe)-type materials, Fe(BDC)(DMF,F), were prepared by using different ratios of n(FeCl3)/n(FeCl2), which have varied amounts of Fe(2+) in their frameworks. From FeCl3 to FeCl2, the structures of the synthesized samples transform from MIL-53(Fe) to Fe(BDC)(DMF,F). Along with this structure transformation, the crystal morphology goes through a striking change from a small irregular shape to a big triangular prism. This phenomenon indicates that the addition of FeCl2 is beneficial for the formation of a Fe(BDC)(DMF,F) structure. The catalytic activity of these iron-containing MOFs was tested in phenol degradation with hydrogen peroxide as an oxidant at near neutral pH and 35 degrees C. The degradation efficiency of these samples increases gradually from MIL-53(Fe) to Fe(BDC)(DMF,F). (57)Fe Mossbauer spectra reveal that Fe(2+) and Fe(3+) coexist in the Fe(BDC)(DMF,F) framework, and the highest amount of Fe(2+) in the sample prepared with mixed FeCl3 and FeCl2 is 26.0%. The result illustrates that the amount of Fe(2+) in the samples can be controlled using varied n(FeCl3)/n(FeCl2) in the feed. The diverse amount of Fe(2+) in this series of FeMOF materials exactly explains the distinction of reaction efficiency. The iron leaching tests, structures of the fresh and used catalysts, and the data of the recycling runs show that the Fe-containing MOFs are stable in this liquid phase reaction. PMID- 26862864 TI - Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives. AB - Molecules bearing trifluoromethoxy (OCF3) group often show desired pharmacological and biological properties. However, facile synthesis of trifluoromethoxylated aromatic compounds remains a formidable challenge in organic synthesis. Conventional approaches often suffer from poor substrate scope, or require use of highly toxic, difficult-to-handle, and/or thermally labile reagents. Herein, we report a user-friendly protocol for the synthesis of methyl 4-acetamido-3-(trifluoromethoxy)benzoate using 1-trifluoromethyl-1,2 benziodoxol-3(1H)-one (Togni reagent II). Treating methyl 4-(N hydroxyacetamido)benzoate (1a) with Togni reagent II in the presence of a catalytic amount of cesium carbonate (Cs2CO3) in chloroform at RT afforded methyl 4-(N-(trifluoromethoxy)acetamido)benzoate (2a). This intermediate was then converted to the final product methyl 4-acetamido-3-(trifluoromethoxy)benzoate (3a) in nitromethane at 120 degrees C. This procedure is general and can be applied to the synthesis of a broad spectrum of ortho-trifluoromethoxylated aniline derivatives, which could serve as useful synthetic building blocks for the discovery and development of new pharmaceuticals, agrochemicals, and functional materials. PMID- 26862869 TI - Large Perovskite Grain Growth in Low-Temperature Solution-Processed Planar p-i-n Solar Cells by Sodium Addition. AB - Thin-film p-i-n type planar heterojunction perovskite solar cells have the advantage of full low temperature solution processability and can, therefore, be adopted in roll-to-roll production and flexible devices. One of the main challenges with these devices, however, is the ability to finely control the film morphology during the deposition and crystallization of the perovskite layer. Processes suitable for optimization of the perovskite layer film morphology with large grains are highly desirable for reduced recombination of charge carriers. Here, we show how uniform thin films with micron size perovskite grains can be made through the use of a controlled amount of sodium ions in the precursor solution. Large micrometer-size CH3NH3PbI3 perovskite grains are formed during low-temperature thin-film growth by adding sodium ions to the PbI2 precursor solution in a two-step interdiffusion process. By adjusting additive concentration, film morphologies were optimized and the fabricated p-i-n planar perovskite-PCBM solar cells showed improved power conversion efficiences (an average of 3-4% absolute efficiency enhancement) compared to the nonsodium based devices. Overall, the additive enhanced grain growth process helped to reach a high 14.2% solar cell device efficiency with low hysteresis. This method of grain growth is quite general and provides a facile way to fabricate large-grained CH3NH3PbI3 on any arbitrary surface by an all solution-processed route. PMID- 26862865 TI - Ambient Fine Particulate Matter, Nitrogen Dioxide, and Preterm Birth in New York City. AB - BACKGROUND: Recent studies have suggested associations between air pollution and various birth outcomes, but the evidence for preterm birth is mixed. OBJECTIVE: We aimed to assess the relationship between air pollution and preterm birth using 2008-2010 New York City (NYC) birth certificates linked to hospital records. METHODS: We analyzed 258,294 singleton births with 22-42 completed weeks gestation to nonsmoking mothers. Exposures to ambient fine particles (PM2.5) and nitrogen dioxide (NO2) during the first, second, and cumulative third trimesters within 300 m of maternal address were estimated using data from the NYC Community Air Survey and regulatory monitors. We estimated the odds ratio (OR) of spontaneous preterm (gestation < 37 weeks) births for the first- and second trimester exposures in a logistic mixed model, and the third-trimester cumulative exposures in a discrete time survival model, adjusting for maternal characteristics and delivery hospital. Spatial and temporal components of estimated exposures were also separately analyzed. RESULTS: PM2.5 was not significantly associated with spontaneous preterm birth. NO2 in the second trimester was negatively associated with spontaneous preterm birth in the adjusted model (OR = 0.90; 95% CI: 0.83, 0.97 per 20 ppb). Neither pollutant was significantly associated with spontaneous preterm birth based on adjusted models of temporal exposures, whereas the spatial exposures showed significantly reduced odds ratios (OR = 0.80; 95% CI: 0.67, 0.96 per 10 MUg/m3 PM2.5 and 0.88; 95% CI: 0.79, 0.98 per 20 ppb NO2). Without adjustment for hospital, these negative associations were stronger. CONCLUSION: Neither PM2.5 nor NO2 was positively associated with spontaneous preterm delivery in NYC. Delivery hospital was an important spatial confounder. CITATION: Johnson S, Bobb JF, Ito K, Savitz DA, Elston B, Shmool JL, Dominici F, Ross Z, Clougherty JE, Matte T. 2016. Ambient fine particulate matter, nitrogen dioxide, and preterm birth in New York City. Environ Health Perspect 124:1283-1290; http://dx.doi.org/10.1289/ehp.1510266. PMID- 26862879 TI - A dose-response relationship between long working hours and unmet need for access to hospital facilities. AB - OBJECTIVES: Lack of access to hospital facilities, indicating unmet healthcare need, plays an important role in health inequity in the workplace. We aimed to investigate the association between long working hours and unmet healthcare need. METHODS: We used data from the Korea National Health and Nutrition Examination Surveys collected during 2007-2012, which included 8369 participants (4765 males, 3604 females) aged 20-54 years, who were paid workers. We used a logistic regression model with gender stratification to investigate the association between working hours and unmet healthcare need. RESULTS: Of the 8369 participants, 855 males (17.94%) and 981 females (27.22%) experienced unmet healthcare need. After adjusting for covariates, and compared to 30-39 working hours per week, the odds ratios (OR) of unmet healthcare need were 1.07 [(95% confidence interval (95% CI) 0.76-1.51], 1.46 (95% CI 1.03-2.07), and 1.57 (95% CI 1.11-2.23) in males, and 1.13 (95% CI 0.92-1.40), 1.30 (95% CI 0.99-1.69), and 1.60 (95% CI 1.21-2.10) in females, for 40-49, 50-59, and >= 60 work hours per week, respectively. There was a dose-response relationship between working hours per week and unmet healthcare need in both genders. CONCLUSIONS: Those who work long hours are more likely to have unmet healthcare needs, the cause of which seems to be lack of time. PMID- 26862866 TI - Lanthanides: Applications in Cancer Diagnosis and Therapy. AB - Lanthanide complexes are of increasing importance in cancer diagnosis and therapy, owing to the versatile chemical and magnetic properties of the lanthanide-ion 4f electronic configuration. Following the first implementation of gadolinium(III)-based contrast agents in magnetic resonance imaging in the 1980s, lanthanide-based small molecules and nanomaterials have been investigated as cytotoxic agents and inhibitors, in photodynamic therapy, radiation therapy, drug/gene delivery, biosensing, and bioimaging. As the potential utility of lanthanides in these areas continues to increase, this timely review of current applications will be useful to medicinal chemists and other investigators interested in the latest developments and trends in this emerging field. PMID- 26862880 TI - One-Pot Procedure for Recovery of Gallic Acid from Wastewater and Encapsulation within Protein Particles. AB - A whey protein isolate solution was heat-denatured and treated with the enzyme transglutaminase, which cross-linked ~26% of the amino groups and increased the magnitude of the zeta-potential value. The protein solution was microemulsified, and then the resulting water-in-oil microemulsion was dispersed within a gallic acid-rich model wastewater. Gallic acid extraction by the outlined microemulsion liquid membrane (MLM) from the exterior aqueous phase (wastewater) and accumulation within the internal aqueous nanodroplets induced protein cold-set gelation and resulted in the formation of gallic acid-enveloping nanoparticles. Measurements with a strain-controlled rheometer indicated a progressive increase in the MLM viscosity during gallic acid recovery corresponding to particle formation. The mean hydrodynamic size of the nanoparticles made from the heat denatured and preheated enzymatically cross-linked proteins was 137 and 122 nm, respectively. The enzymatic cross-linking of whey proteins led to a higher gallic acid recovery yield and increased the glass transition enthalpy and temperature. A similar impact on glass transition indices was observed by the gallic acid induced nanoparticulation of proteins. Scanning electron microscopy showed the existence of numerous jammed/fused nanoparticles. It was suggested on the basis of the results of Fourier transform infrared spectroscopy that the in situ nanoparticulation of proteins shifted the C-N stretching and C-H bending peaks to higher wavenumbers. X-ray diffraction results proposed a decreased beta-sheet content for proteins because of the acid-induced particulation. The nanoparticles made from the enzymatically cross-linked protein were more stable against the in vitro gastrointestinal digestion and retained almost 19% of the entrapped gallic acid after 300 min sequential gastric and intestinal digestions. PMID- 26862881 TI - Synthesis of gold Nanoshells through Improved Seed-Mediated Growth Approach: Brust-like, in Situ Seed Formation. AB - Gold nanoshells have shown great potentials in various fields. However, the widely used seed-mediated growth method based on a silica template for gold nanoshells is a complex and time-consuming procedure. In this work, mercaptosilica was first used as a template to synthesize gold nanoshells through improved seed-mediated growth method. It is verified that gold seeds were formed and attached onto the mercaptosilica nanospheres through Brust-like, in situ process, which makes this method extremely time-saving and easy to manipulate. Importantly, the key factors affecting the in situ process were demonstrated, allowing fine control on the synthesis in a highly reproducible manner. The as synthesized nanoshells are monodisperse with well-defined morphology and tunable near-IR plasmon resonance. Furthermore, other metal nanoparticles such as Pt and Pd could be grafted onto the surface of mercaptosilica nanospheres through the same Brust-like, in situ process. These provide new insights into seed attachment, and the improved seed-mediated growth approach based on Brust-like, in situ seed formation will take an important step forward toward the widespread application of gold nanoshells. PMID- 26862882 TI - The good, the bad and the user in soft matter simulations. AB - Molecular dynamics (MD) simulations have become popular in materials science, biochemistry, biophysics and several other fields. Improvements in computational resources, in quality of force field parameters and algorithms have yielded significant improvements in performance and reliability. On the other hand, no method of research is error free. In this review, we discuss a few examples of errors and artifacts due to various sources and discuss how to avoid them. Besides bringing attention to artifacts and proper practices in simulations, we also aim to provide the reader with a starting point to explore these issues further. In particular, we hope that the discussion encourages researchers to check software, parameters, protocols and, most importantly, their own practices in order to minimize the possibility of errors. The focus here is on practical issues. This article is part of a Special Issue entitled: Biosimulations edited by Ilpo Vattulainen and Tomasz Rog. PMID- 26862883 TI - Probing the Dynamics of Rydberg and Valence States of Molecular Nitrogen with Attosecond Transient Absorption Spectroscopy. AB - An attosecond pulse is used to create a wavepacket in molecular nitrogen composed of multiple bound and autoionizing electronic states of Rydberg and valence character between 12 and 16.7 eV. A time-delayed, few-femtosecond, near-infrared (NIR) laser pulse is used to couple individual states in the wavepacket to multiple neighboring states, resulting in time-dependent modification of the absorption spectrum and revealing both individual quantum beats of the wavepacket and the energy shifts of the excited states in the presence of the strong NIR field. The broad bandwidth of the attosecond pulse and high energy resolution of the extreme ultraviolet spectrometer allow the simultaneous observation of time dependent dynamics for many individual vibrational levels in each electronic state. Quantum beating with periods from 1.3 to 12 fs and transient line shape changes are observed among vibrational levels of a progression of electronically autoionizing Rydberg states leading to the excited A (2)Piu N2(+) ion core. Vibrational levels in the valence b (1)Piu state exhibit 50 fs oscillation periods, revealing superpositions between individual vibrational levels within this state. Comparisons are made to previous studies of electronic wavepackets in atoms that highlight similarities to atomic behavior yet illustrate unique contributions of the diatomic molecular structure to the wavepacket, including the influence of different electronic potentials and vibrational-level-specific electronic dynamics. PMID- 26862884 TI - Fluoride-induced c-Fos expression in MC3T3-E1 osteoblastic cells. AB - Excessive systemic exposure to fluoride leads to disturbances of bone homeostasis. c-Fos is known to be essential in bone development by affecting osteoblast and osteoclast differentiation. In this study, we examined the effects of fluoride exposure on c-Fos expression and its regulatory signaling pathways in MC3T3-E1 mouse osteoblast cell line. c-fos mRNA level, c-Fos protein level and c Fos DNA-binding activity were markedly increased, with a peak at 2 or 4 h, in MC3T3-E1 cells exposed to sodium fluoride (NaF). Fra-1 protein, another member of Fos family, was also elevated, whereas FosB and Fra-2 proteins remained unchanged. NaF further induced phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated protein kinase 1/2 (ERK1/2), ERK5, c-Jun NH2-terminal kinase and p38. NaF-induced expression of c Fos protein was markedly suppressed with U0126, the inhibitor of both activated and non-activated forms of MAPK/ERK kinase 1/2 (MEK1/2) and BIX02189, the MEK5 inhibitor, but partially with SP600125, the JNK inhibitor and SB203580, the p38 inhibitor. Therefore, ERK1/2 and ERK5 signal transduction pathways are important for accumulating c-Fos. siRNA targeting against the mouse c-fos gene further enhanced NaF-induced up-regulation of osteoprotegerin (OPG), an inhibitor of osteoclastogenesis, suggesting that c-Fos might negatively regulate OPG expression induced by fluoride in osteoblastic cells. PMID- 26862885 TI - Electronic Structure and Phase Stability of PdPt Nanoparticles. AB - To understand the origin of the physicochemical nature of bimetallic PdPt nanoparticles, we theoretically investigated the phase stability and electronic structure employing the PdPt nanoparticles models consisting of 711 atoms (ca. 3 nm). For the Pd-Pt core-shell nanoparticle, the PdPt solid-solution phase was found to be a thermodynamically stable phase in the nanoparticle as the result of difference in surface energy of Pd and Pt nanoparticles and configurational entropy effect, while it is well known that the Pd and Pt are the immiscible combination in the bulk phase. The electronic structure of nanoparticles is conducted to find that the electron transfer occurs locally within surface and subsurface layers. In addition, the electron transfer from Pd to Pt at the interfacial layers in core-shell nanoparticles is observed, which leads to unique geometrical and electronic structure changes. Our results show a clue for the tunability of the electronic structure of nanoparticles by controlling the arrangement in the nanoparticles. PMID- 26862886 TI - Pyrolysis Treatment of Chromite Ore Processing Residue by Biomass: Cellulose Pyrolysis and Cr(VI) Reduction Behavior. AB - The pyrolysis treatment with biomass is a promising technology for the remediation of chromite-ore-processing residue (COPR). However, the mechanism of this process is still unclear. In this study, the behavior of pyrolysis reduction of Cr(VI) by cellulose, the main component of biomass, was elucidated. The results showed that the volatile fraction (VF) of cellulose, ie. gas and tar, was responsible for Cr(VI) reduction. All organic compounds, as well as CO and H2 in VF, potentially reduced Cr(VI). X-ray absorption near-edge structure (XANES) spectroscopy and extended X-ray absorption fine-structure (EXAFS) spectroscopy confirmed the reduction of Cr(VI) to Cr(III) and the formation of amorphous Cr2O3. The remnant Cr(VI) content in COPR can be reduced below the detection limit (2 mg/kg) by the reduction of COPR particle and extension of reaction time between VF and COPR. This study provided a deep insight on the co-pyrolysis of cellulose with Cr(VI) in COPR and an ideal approach by which to characterize and optimize the pyrolysis treatment for COPR by other organics. PMID- 26862887 TI - Trends in Smoking Status and Utilization of Smoking Cessation Agents Among Females with Cardiovascular Diseases. AB - BACKGROUND: In the United States, cigarette smoking accounts for almost 20% of all deaths attributed to heart disease. More women than men die each year of cardiovascular diseases (CVDs). Women who smoke have shown to be at a higher risk of cardiac deaths. The current study aims to determine the trend in smoking prevalence among women with CVD and their utilization of smoking cessation agents from 2004 to 2011. MATERIALS AND METHODS: This was a retrospective exploratory study using Medical Expenditure Panel Survey data from 2004 to 2011. All female respondents with any one cardiovascular condition were identified. Descriptive statistics were carried out to obtain the number of female patients with CVD, their smoking status, and their use of smoking cessation agents. Furthermore, disparities in smoking status and smoking cessation agent utilization with respect to race and ethnicity were studied. RESULTS: Among total CVD patients, 53% were females, which corresponded to 25.3 million females in the United States. Around 12.3% among them were current smokers. Only 6.9% among these females used smoking cessation agents. Smoking trends in females were inconsistent throughout the 8 years. Overall, the trend showed a decrease in the percentage of female smokers, while use of smoking cessation agents remained low from 2004 to 2011. Whites and non-Hispanics had more current smokers and women using smoking cessation agents. CONCLUSION: The eight-year trend shows that the use of smoking cessation agents among females is very low, particularly among non whites and Hispanics. This is of great concern and future efforts could focus on increasing the utilization of smoking cessation agents and collectively decreasing the risk of smoking in CVD by healthcare professionals. PMID- 26862889 TI - Lewis Acid Catalyzed [4 + 3] Cycloaddition of Propargylic Alcohols with Azides. AB - An unprecedented Lewis acid catalyzed [4 + 3] cycloaddition reaction is described that provides a straightforward route to polycyclic products containing an imine based indole azepine scaffold, starting from readily available internal tertiary alkynols and azides. This cycloaddition protocol provides efficient and atom economical access to a new class of fascinating imine-containing products in satisfactory yields, which has shown good application in the construction of seven-membered N-heterocycles. PMID- 26862890 TI - Development and Validation of a Bronchoscopy Competence Assessment Tool in a Clinical Setting. AB - RATIONALE: Flexible bronchoscopy is performed by clinicians representing multiple medical specialties in a variety of settings. Given the increasing importance of competency-based assessment in postgraduate training, it is important that this skill be assessed within a competency-based framework using a valid measurement tool. OBJECTIVES: The purpose of this study was to design and validate a practical, competency-based bronchoscopy assessment tool that could be applied to trainees in a clinical setting. METHODS: Focus groups of expert physicians were formed in Ottawa, Canada representing adult medical specialties routinely engaged in preparing trainees to perform flexible bronchoscopy (respiratory medicine, critical care, thoracic surgery and anesthesia). The focus groups were charged with identifying themes and items relevant to the assessment of competency in bronchoscopy. By an iterative process, a bronchoscopy assessment tool was developed, the Ontario Bronchoscopy Assessment Tool (OBAT). The tool was evaluated by first using it to assess learners in a pilot study, refining it based on the results, and then testing the OBAT again in a validation study. MEASUREMENTS AND MAIN RESULTS: The initial tool consisted of 19 items, organized into the following groups: preprocedure planning, sedation and monitoring, technical skill, diagnostic skill, and post-procedure planning. The tool demonstrated high reliability (0.91) and discriminated junior from senior trainees. Based on the results of the pilot, the tool was simplified to a 12-item scale with three subscales: preprocedure planning, technical skills, and post procedure planning. In the validation study, the assessment tool remained highly reliable (0.92) and discriminated junior from senior trainees with an estimated eight assessments per trainee. CONCLUSIONS: The OBAT demonstrates promise as a reliable tool to assess trainee competence for bronchoscopy in clinical settings. PMID- 26862891 TI - Using uterine activity to improve fetal heart rate variability analysis for detection of asphyxia during labor. AB - During labor, uterine contractions can cause temporary oxygen deficiency for the fetus. In case of severe and prolonged oxygen deficiency this can lead to asphyxia. The currently used technique for detection of asphyxia, cardiotocography (CTG), suffers from a low specificity. Recent studies suggest that analysis of fetal heart rate variability (HRV) in addition to CTG can provide information on fetal distress. However, interpretation of fetal HRV during labor is difficult due to the influence of uterine contractions on fetal HRV. The aim of this study is therefore to investigate whether HRV features differ during contraction and rest periods, and whether these differences can improve the detection of asphyxia. To this end, a case-control study was performed, using 14 cases with asphyxia that were matched with 14 healthy fetuses. We did not find significant differences for individual HRV features when calculated over the fetal heart rate without separating contractions and rest periods (p > 0.30 for all HRV features). Separating contractions from rest periods did result in a significant difference. In particular the ratio between HRV features calculated during and outside contractions can improve discrimination between fetuses with and without asphyxia (p < 0.04 for three out of four ratio HRV features that were studied in this paper). PMID- 26862893 TI - Intake and Biomarkers of Folate and Risk of Cancer Morbidity in Older Adults, NHANES 1999-2002 with Medicare Linkage. AB - BACKGROUND: After the 1998 mandatory folic acid fortification of enriched cereal grain products in the U.S., safety concerns were raised that excess consumption of folic acid and high blood folate biomarkers detected in adults may increase the risk of certain types of cancer. METHODS: Baseline data from about 1400 participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2002, aged >= 57 years were linked to Medicare and mortality files through December 31, 2007. Using cox proportional hazards regression models, we assessed associations between dietary folate equivalents, folate biomarkers, the presence of unmetabolized folic acid and, overall cancer incidence. RESULTS: With 8,114 person-years of follow-up (median follow-up, 6.3 years), about 125 cancer cases were identified. After adjusting for confounders, the hazard ratios of the highest quartile versus the second quartile of RBC folate and dietary folate equivalents were 0.54 (95% CI: 0.31-0.93) and 0.54 (95% CI: 0.30-0.95), respectively. Additionally, serum and RBC folate as continuous variables were inversely and significantly associated with cancer incidence (p<0.01). No significant associations were observed between the presence of unmetabolized folic acid, intake of naturally-occurring food folate or folic acid separately, and cancer incidence. CONCLUSIONS: High total folate intake and biomarkers in older adults appear to be protective against cancer in post-folic acid fortification years. This study does not show a negative impact of current level of folic acid fortification on cancer risk. As this is one of the few studies to examine the association between unmetabolized folic acid and cancer outcome, a study including a larger nationwide representative sample of the U.S. population is needed. PMID- 26862892 TI - Functional Dentition in Brazilian Adults: An Investigation of Social Determinants of Health (SDH) Using a Multilevel Approach. AB - OBJECTIVES: Estimate the prevalence of functional dentition among Brazilian adults using four different definitions and identify associated factors. METHODS: A cross-sectional study was conducted involving 9564 Brazilian adults aged 35-44 years who participated in the 2010 National Oral Health Survey. Data collection involved oral examinations and the administration of questionnaires. The following definitions were used: 1-WHO Functional Dentition (FDWHO: >= 20 teeth present); 2-well-distributed teeth (WDT: >= 10 teeth in each arch); 3 -Functional dentition classified by esthetics and occlusion (FDClass5: dentitions that sequentially exhibit at least one tooth in each arch, at least 10 teeth in each arch, all maxillary and mandibular anterior teeth, three or four premolar posterior occluding pairs [POPs], and at least one molar POP bilaterally); 4 Functional dentition classified by esthetics, occlusion and periodontal status (FDClass6: corresponds to FDClass5 with the addition of periodontal status of all sextants in the oral cavity with, at most, shallow pockets and/or clinical attachment level of 5 mm (CPI <= 3 and/or CAL <= 1). The independent variables were individual factors (gender, self-declared skin color, schooling, monthly household income, age group, self-rated treatment need, dental pain, dental appointment in the previous 12 months and dental services) and contextual factors (Municipal Human Development Index [MHDI]), Gini coefficient, fluoridated water supply and oral health coverage). Multilevel mixed-effect Poisson regression analyses were performed. RESULTS: The prevalence of functional dentition based on the FDWHO, WDT, FDClass5 and FDClass6 definitions was 77.9%, 72.9%, 42.6% and 40.3%, respectively. Adults with >=12 years of schooling and monthly household income from US$ 853 to 2557 had higher prevalence rates of FDWHO (PR: 1.41 and 1.10, respectively), WDT (PR: 1.58 and 1.14, respectively), FDClass5 (PR: 2.03 and 1.27, respectively) and FDClass6 (PR: 2.15 and 1.35, respectively). These values in the final models were adjusted for gender, self-declared skin color (FDClass5), age group, self-rated treatment need (FDWHO, FDClass5 and FDClass6), dental appointment in the previous 12 months (FDWHO and WDT), dental services (FDWHO and WDT) and contextual factors. A very high MHDI and presence of fluoridated water supply were associated with higher prevalence rates of the four outcomes. CONCLUSIONS: The incorporation of the criteria of new definitions of functional dentition led to a lower prevalence rate among Brazilian adults. Striking individual and contextual inequalities were identified with regard to the four definitions analyzed, which need to be addressed through inter-sector efforts. PMID- 26862895 TI - Predicting Effects of Water Regime Changes on Waterbirds: Insights from Staging Swans. AB - Predicting the environmental impact of a proposed development is notoriously difficult, especially when future conditions fall outside the current range of conditions. Individual-based approaches have been developed and applied to predict the impact of environmental changes on wintering and staging coastal bird populations. How many birds make use of staging sites is mostly determined by food availability and accessibility, which in the case of many waterbirds in turn is affected by water level. Many water systems are regulated and water levels are maintained at target levels, set by management authorities. We used an individual based modelling framework (MORPH) to analyse how different target water levels affect the number of migratory Bewick's swans Cygnus columbianus bewickii staging at a shallow freshwater lake (Lauwersmeer, the Netherlands) in autumn. As an emerging property of the model, we found strong non-linear responses of swan usage to changes in water level, with a sudden drop in peak numbers as well as bird-days with a 0.20 m rise above the current target water level. Such strong non-linear responses are probably common and should be taken into account in environmental impact assessments. PMID- 26862894 TI - Global Patterns of QALY and DALY Use in Surgical Cost-Utility Analyses: A Systematic Review. AB - BACKGROUND: Surgical interventions are being increasingly recognized as cost effective global priorities, the utility of which are frequently measured using either quality-adjusted (QALY) or disability-adjusted (DALY) life years. The objectives of this study were to: (1) identify surgical cost-effectiveness studies that utilized a formulation of the QALY or DALY as a summary measure, (2) report on global patterns of QALY and DALY use in surgery and the income characteristics of the countries and/or regions involved, and (3) assess for possible associations between national/regional-income levels and the relative prominence of either measure. STUDY DESIGN: PRISMA-guided systematic review of surgical cost-effectiveness studies indexed in PubMed or EMBASE prior to December 15, 2014, that used the DALY and/or QALY as a summary measure. National locations were used to classify publications based on the 2014 World Bank income stratification scheme into: low-, lower-middle-, upper-middle-, or high-income countries. Differences in QALY/DALY use were considered by income level as well as for differences in geographic location and year using descriptive statistics (two-sided Chi-squared tests, Fischer's exact tests in cell counts <5). RESULTS: A total of 540 publications from 128 countries met inclusion criteria, representing 825 "national studies" (regional publications included data from multiple countries). Data for 69.0% (569/825) were reported using QALYs (2.1% low , 1.2% lower-middle-, 4.4% upper-middle-, and 92.3% high-income countries), compared to 31.0% (256/825) reported using DALYs (46.9% low-, 31.6% lower-middle , 16.8% upper-middle-, and 4.7% high-income countries) (p<0.001). Studies from the US and the UK dominated the total number of QALY studies (49.9%) and were themselves almost exclusively QALY-based. DALY use, in contrast, was the most common in Africa and Asia. While prominent published use of QALYs (1990s) in surgical cost-effectiveness studies began approximately 10 years earlier than DALYs (2000s), the use of both measures continues to increase. CONCLUSION: As global prioritization of surgical interventions gains prominence, it will be important to consider the comparative implications of summary measure use. The results of this study demonstrate significant income- and geographic-based differences in the preferential utilization of the QALY and DALY for surgical cost-effectiveness studies. Such regional variation holds important implications for efforts to interpret and utilize global health policy research. PROSPERO registration number: CRD42015015991. PMID- 26862896 TI - Does Marriage Make Us Healthier? Inter-Country Comparative Evidence from China, Japan, and Korea. AB - OBJECTIVES: This study focuses on East Asian countries and investigates the difference in the marriage premium on the health-marriage protection effect (MPE) between younger and older generations and the intra-couple education concordance effect (ECE) on the health of married individuals. This study used inter-country comparative data from China, Japan, and Korea. METHODS: This study focused on individuals (n = 7,938) in China, Japan, and Korea who were sampled from the 2010 East Asian Social Survey. To investigate MPE and ECE, four health indicators were utilized: a physical and mental components summary (PCS and MCS), self-rated health status (Dself), and happiness level (Dhappy). Ordinary least squares regression was conducted by country- and gender-specific subsamples. RESULTS: We found that the MPE on PCS, MCS, and Dself was more significant for the older generation than for the younger generation in both China and Japan, whereas the results were inconclusive in Korea. With regard to the ECE on happiness (Dhappy), for both men and women, couples tend to be happier when both the husband and the wife are well educated ("higher balanced marriage") compared to couples with a lower level of educational achievement ("lower balanced marriage"). Significant benefits from a "higher balanced marriage" on MCS and Dself were observed for women only. In contrast, no statistically significant differences in health status were observed between "higher balanced marriage" couples and couples with different levels of educational achievements ("upward marriage" or "downward marriage"). CONCLUSIONS: This study found that (1) the MPE was more significant for the older generation, and (2) the health gap, particularly the happiness gap, between higher- and lower-balanced married couples was significant. The inter country comparative findings are useful to explain how the role of marriage (and therefore of family) on health has been diluted due to the progress of industrialization and modernization. PMID- 26862897 TI - Water-Transfer Slows Aging in Saccharomyces cerevisiae. AB - Transferring Saccharomyces cerevisiae cells to water is known to extend their lifespan. However, it is unclear whether this lifespan extension is due to slowing the aging process or merely keeping old yeast alive. Here we show that in water-transferred yeast, the toxicity of polyQ proteins is decreased and the aging biomarker 47Q aggregates at a reduced rate and to a lesser extent. These beneficial effects of water-transfer could not be reproduced by diluting the growth medium and depended on de novo protein synthesis and proteasomes levels. Interestingly, we found that upon water-transfer 27 proteins are downregulated, 4 proteins are upregulated and 81 proteins change their intracellular localization, hinting at an active genetic program enabling the lifespan extension. Furthermore, the aging-related deterioration of the heat shock response (HSR), the unfolded protein response (UPR) and the endoplasmic reticulum-associated protein degradation (ERAD), was largely prevented in water-transferred yeast, as the activities of these proteostatic network pathways remained nearly as robust as in young yeast. The characteristics of young yeast that are actively maintained upon water-transfer indicate that the extended lifespan is the outcome of slowing the rate of the aging process. PMID- 26862898 TI - Genetic and Environmental Regulation on Longitudinal Change of Metabolic Phenotypes in Danish and Chinese Adult Twins. AB - OBJECTIVE: The rate of change in metabolic phenotypes can be highly indicative of metabolic disorders and disorder-related modifications. We analyzed data from longitudinal twin studies on multiple metabolic phenotypes in Danish and Chinese twins representing two populations of distinct ethnic, cultural, social-economic backgrounds and geographical environments. MATERIALS AND METHODS: The study covered a relatively large sample of 502 pairs of Danish adult twins followed up for a long period of 12 years with a mean age at intake of 38 years (range: 18 65) and a total of 181 Chinese adult twin pairs traced for about 7 years with a mean baseline age of 39.5 years (range: 23-64). The classical twin models were fitted to the longitudinal change in each phenotype (Deltaphenotype) to estimate the genetic and environmental contributions to the variation in Deltaphenotype. RESULTS: Moderate to high contributions by the unique environment were estimated for all phenotypes in both Danish (from 0.51 for low density lipoprotein cholesterol up to 0.72 for triglycerides) and Chinese (from 0.41 for triglycerides up to 0.73 for diastolic blood pressure) twins; low to moderate genetic components were estimated for long-term change in most of the phenotypes in Danish twins except for triglycerides and hip circumference. Compared with Danish twins, the Chinese twins tended to have higher genetic control over the longitudinal changes in lipids (except high density lipoprotein cholesterol) and glucose, higher unique environmental contribution to blood pressure but no genetic contribution to longitudinal change in body mass traits. CONCLUSION: Our results emphasize the major contribution of unique environment to the observed intra-individual variation in all metabolic phenotypes in both samples, and meanwhile reveal differential patterns of genetic and common environmental regulation on changes over time in metabolic phenotypes across the two samples. PMID- 26862888 TI - Role of Thyroid Hormones in Skeletal Development and Bone Maintenance. AB - The skeleton is an exquisitely sensitive and archetypal T3-target tissue that demonstrates the critical role for thyroid hormones during development, linear growth, and adult bone turnover and maintenance. Thyrotoxicosis is an established cause of secondary osteoporosis, and abnormal thyroid hormone signaling has recently been identified as a novel risk factor for osteoarthritis. Skeletal phenotypes in genetically modified mice have faithfully reproduced genetic disorders in humans, revealing the complex physiological relationship between centrally regulated thyroid status and the peripheral actions of thyroid hormones. Studies in mutant mice also established the paradigm that T3 exerts anabolic actions during growth and catabolic effects on adult bone. Thus, the skeleton represents an ideal physiological system in which to characterize thyroid hormone transport, metabolism, and action during development and adulthood and in response to injury. Future analysis of T3 action in individual skeletal cell lineages will provide new insights into cell-specific molecular mechanisms and may ultimately identify novel therapeutic targets for chronic degenerative diseases such as osteoporosis and osteoarthritis. This review provides a comprehensive analysis of the current state of the art. PMID- 26862899 TI - GABA and Endocannabinoids Mediate Depotentiation of Schaffer Collateral Synapses Induced by Stimulation of Temperoammonic Inputs. AB - Long-term potentiation (LTP) of Schaffer collateral (SC) synapses in the hippocampus is thought to play a key role in episodic memory formation. Because the hippocampus is a shorter-term, limited capacity storage system, repeated bouts of learning and synaptic plasticity require that SC synapses reset to baseline at some point following LTP. We previously showed that repeated low frequency activation of temperoammonic (TA) inputs to the CA1 region depotentiates SC LTP without persistently altering basal transmission. This heterosynaptic depotentiation involves adenosine A1 receptors but not N-methyl-D aspartate receptors, metabotropic glutamate receptors or L-type calcium channels. In the present study, we used rat hippocampal slices to explore other messengers contributing to TA-induced SC depotentiation, and provide evidence for the involvement of cannabinoid-1 and gamma-aminobutyric acid (GABA) type-A receptors as more proximal signaling events leading to synaptic resetting, with A1 receptor activation serving as a downstream event. Surprisingly, we found that TA-induced SC depotentiation is independent of alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid (AMPA)/kainate glutamate receptors. We also examined the involvement of mitogen-activated protein kinases (MAPKs), and found a role for extracellular-signal related kinase 1/2 and p38 MAPK, but not c-Jun-N-terminal kinase. These results indicate that low frequency stimulation of TA inputs to CA1 activates a complex signaling network that instructs SC synaptic resetting. The involvement of GABA and endocannabinoids suggest mechanisms that could contribute to cognitive dysfunction associated with substance abuse and neuropsychiatric disorders. PMID- 26862901 TI - Oral Efficacy of Apigenin against Cutaneous Leishmaniasis: Involvement of Reactive Oxygen Species and Autophagy as a Mechanism of Action. AB - BACKGROUND: The treatment for leishmaniasis is currently based on pentavalent antimonials and amphotericin B; however, these drugs result in numerous adverse side effects. The lack of affordable therapy has necessitated the urgent development of new drugs that are efficacious, safe, and more accessible to patients. Natural products are a major source for the discovery of new and selective molecules for neglected diseases. In this paper, we evaluated the effect of apigenin on Leishmania amazonensis in vitro and in vivo and described the mechanism of action against intracellular amastigotes of L. amazonensis. METHODOLOGY/PRINCIPAL FINDING: Apigenin reduced the infection index in a dose dependent manner, with IC50 values of 4.3 MUM and a selectivity index of 18.2. Apigenin induced ROS production in the L. amazonensis-infected macrophage, and the effects were reversed by NAC and GSH. Additionally, apigenin induced an increase in the number of macrophages autophagosomes after the infection, surrounding the parasitophorous vacuole, suggestive of the involvement of host autophagy probably due to ROS generation induced by apigenin. Furthermore, apigenin treatment was also effective in vivo, demonstrating oral bioavailability and reduced parasitic loads without altering serological toxicity markers. CONCLUSIONS/SIGNIFICANCE: In conclusion, our study suggests that apigenin exhibits leishmanicidal effects against L. amazonensis-infected macrophages. ROS production, as part of the mechanism of action, could occur through the increase in host autophagy and thereby promoting parasite death. Furthermore, our data suggest that apigenin is effective in the treatment of L. amazonensis-infected BALB/c mice by oral administration, without altering serological toxicity markers. The selective in vitro activity of apigenin, together with excellent theoretical predictions of oral availability, clear decreases in parasite load and lesion size, and no observed compromises to the overall health of the infected mice encourage us to supports further studies of apigenin as a candidate for the chemotherapeutic treatment of leishmaniasis. PMID- 26862900 TI - Whole Rye Consumption Improves Blood and Liver n-3 Fatty Acid Profile and Gut Microbiota Composition in Rats. AB - BACKGROUND: Whole rye (WR) consumption seems to be associated with beneficial health effects. Although rye fiber and polyphenols are thought to be bioactive, the mechanisms behind the health effects of WR have yet to be fully identified. This study in rats was designed to investigate whether WR can influence the metabolism of n-3 and n-6 long-chain fatty acids (LCFA) and gut microbiota composition. METHODS: For 12 weeks, rats were fed a diet containing either 50% WR or 50% refined rye (RR). The WR diet provided more fiber (+21%) and polyphenols (+29%) than the RR diet. Fat intake was the same in both diets and particularly involved similar amounts of essential (18-carbon) n-3 and n-6 LCFAs. RESULTS: The WR diet significantly increased the 24-hour urinary excretion of polyphenol metabolites-including enterolactone-compared with the RR diet. The WR rats had significantly more n-3 LCFA-in particular, eicosapentanoic (EPA) and docosahexanoic (DHA) acids-in their plasma and liver. Compared with the RR diet, the WR diet brought significant changes in gut microbiota composition, with increased diversity in the feces (Shannon and Simpson indices), decreased Firmicutes/Bacteroidetes ratio and decreased proportions of uncultured Clostridiales cluster IA and Clostridium cluster IV in the feces. In contrast, no difference was found between groups with regards to cecum microbiota. The WR rats had lower concentrations of total short-chain fatty acids (SCFA) in cecum and feces (p<0.05). Finally, acetate was lower (p<0.001) in the cecum of WR rats while butyrate was lower (p<0.05) in the feces of WR rats. INTERPRETATION: This study shows for the first time that WR consumption results in major biological modifications-increased plasma and liver n-3 EPA and DHA levels and improved gut microbiota profile, notably with increased diversity-known to provide health benefits. Unexpectedly, WR decreased SCFA levels in both cecum and feces. More studies are needed to understand the interactions between whole rye (fiber and polyphenols) and gut microbiota and also the mechanisms of action responsible for stimulating n-3 fatty acid metabolism. PMID- 26862902 TI - Spatial and temporal characteristics of stable isotopes in the Tarim River Basin. AB - By using 233 isotope samples, we investigated the spatial and temporal variations of delta(18)O and delta(2)H in precipitation and surface water, and the contribution of different water sources in the rivers within the Tarim River Basin (TRB), which receives snow/glacier meltwater, groundwater, and rainfall. Our study revealed a similar seasonal pattern of precipitation delta(18)O and delta(2)H at both the north and south edges of the basin, indicating the dominant effect of westerly air masses in the summer and the combined influence of westerly and polar air masses during the winter, although the southern part showed more complex precipitation processes in the summer. River water in the basin has relatively large temporal variations in both delta(18)O and delta(2)H showing a distinct seasonal pattern with lower isotope values in May than in September. Higher d-excess values throughout the year in the Aksu river and the Tizinafu river suggest that water may be intensively recycled in the mountains of the TRB. Based on isotopic hydrograph separation, we found that groundwater is the main water source that discharges the entire basin although individual rivers vary. PMID- 26862903 TI - Distinguishing Lung Adenocarcinoma from Lung Squamous Cell Carcinoma by Two Hypomethylated and Three Hypermethylated Genes: A Meta-Analysis. AB - Significant differences in the aberrant methylation of genes exist among various histological types of non-small cell lung cancer (NSCLC), which includes adenocarcinoma (AC) and squamous cell carcinoma (SCC). Different chemotherapeutic regimens should be administered to the two NSCLC subtypes due to their unique genetic and epigenetic profiles. The purpose of this meta-analysis was to generate a list of differentially methylated genes between AC and SCC. Our meta analysis encompassed 151 studies on 108 genes among 12946 AC and 10243 SCC patients. Our results showed two hypomethylated genes (CDKN2A and MGMT) and three hypermethylated genes (CDH13, RUNX3 and APC) in ACs compared with SCCs. In addition, our results showed that the pooled specificity and sensitivity values of CDH13 and APC were higher than those of CDKN2A, MGMT and RUNX3. Our findings might provide an alternative method to distinguish between the two NSCLC subtypes. PMID- 26862904 TI - Abscisic Acid Induces Rapid Reductions in Mesophyll Conductance to Carbon Dioxide. AB - The rate of photosynthesis (A) of plants exposed to water deficit is a function of stomatal (gs) and mesophyll (gm) conductance determining the availability of CO2 at the site of carboxylation within the chloroplast. Mesophyll conductance often represents the greatest impediment to photosynthetic uptake of CO2, and a crucial determinant of the photosynthetic effects of drought. Abscisic acid (ABA) plays a fundamental role in signalling and co-ordination of plant responses to drought; however, the effect of ABA on gm is not well-defined. Rose, cherry, olive and poplar were exposed to exogenous ABA and their leaf gas exchange parameters recorded over a four hour period. Application with ABA induced reductions in values of A, gs and gm in all four species. Reduced gm occurred within one hour of ABA treatment in three of the four analysed species; indicating that the effect of ABA on gm occurs on a shorter timescale than previously considered. These declines in gm values associated with ABA were not the result of physical changes in leaf properties due to altered turgor affecting movement of CO2, or caused by a reduction in the sub-stomatal concentration of CO2 (Ci). Increased [ABA] likely induces biochemical changes in the properties of the interface between the sub-stomatal air-space and mesophyll layer through the actions of cooporins to regulate the transport of CO2. The results of this study provide further evidence that gm is highly responsive to fluctuations in the external environment, and stress signals such as ABA induce co-ordinated modifications of both gs and gm in the regulation of photosynthesis. PMID- 26862905 TI - Individual Colorimetric Observer Model. AB - This study proposes a vision model for individual colorimetric observers. The proposed model can be beneficial in many color-critical applications such as color grading and soft proofing to assess ranges of color matches instead of a single average match. We extended the CIE 2006 physiological observer by adding eight additional physiological parameters to model individual color-normal observers. These eight parameters control lens pigment density, macular pigment density, optical densities of L-, M-, and S-cone photopigments, and lambdamax shifts of L-, M-, and S-cone photopigments. By identifying the variability of each physiological parameter, the model can simulate color matching functions among color-normal populations using Monte Carlo simulation. The variabilities of the eight parameters were identified through two steps. In the first step, extensive reviews of past studies were performed for each of the eight physiological parameters. In the second step, the obtained variabilities were scaled to fit a color matching dataset. The model was validated using three different datasets: traditional color matching, applied color matching, and Rayleigh matches. PMID- 26862907 TI - Size, Accumulation and Performance for Research Grants: Examining the Role of Size for Centres of Excellence. AB - The present paper examines the relation between size, accumulation and performance for research grants, where we examine the relation between grant size for Centres of Excellence (CoE) funded by the Danish National Research Foundation (DNRF) and various ex post research performance measures, including impact and shares of highly cited articles. We examine both the relation between size and performance and also how performance for CoEs evolves over the course of grant periods. In terms of dynamics, it appears that performance over the grant period (i.e. 10 years) is falling for the largest CoEs, while it is increasing for those among the smallest half. Overall, multivariate econometric analysis finds evidence that performance is increasing in grant size and over time. In both cases, the relation appears to be non-linear, suggesting that there is a point at which performance peaks. The CoEs have also been very successful in securing additional funding, which can be viewed as a 'cumulative effect' of center grants. In terms of new personnel, the far majority of additional funding is spent on early career researchers, hence, this accumulation would appear to have a 'generational' dimension, allowing for scientific expertise to be passed on to an increasing number of younger researchers. PMID- 26862909 TI - Cancer-related pain management in clinical oncology. AB - Uncontrolled pain is one of the most feared and debilitating symptoms among cancer patients, and many suffer unnecessarily from suboptimal pain control. Cancer-related pain is often multidimensional and can affect all aspects of a patient's life. Hence, achieving adequate pain relief among cancer patients involves a proper assessment of psychosocial, spiritual, and physical pain issues, matched with an individualized treatment plan involving pharmacologic, nonpharmacologic, and procedural therapies when appropriate. Providing effective pain relief can help ease the overall burden of disease among oncology patients while helping them tolerate cancer-directed therapies and achieve the most optimal quality of life throughout all phases of the disease continuum. In this review, the authors will discuss the syndromes, assessment of, and treatment for cancer-related pain in the outpatient setting. PMID- 26862906 TI - Synergistic Effect of Anti-Angiogenic and Radiation Therapy: Quantitative Evaluation with Dynamic Contrast Enhanced MR Imaging. AB - PURPOSE: We assessed the effects of anti-angiogenic therapy (AAT) on radiation therapy (RT), evaluating the tumor growth and perfusion patterns on dynamic contrast enhanced MR (DCE-MR) images. METHODS: Thirteen nude mice with heterotopic xenograft cancer of human lung cancer cell line were used. To observe the interval change of the tumor size and demonstrate the time-signal intensity enhancement curve of the tumor, the mice were subdivided into four groups: control (n = 2), AAT (n = 2), RT (n = 5), and combined therapy (AART, n = 4). DCE MR images were taken four weeks after treatment. Perfusion parameters were obtained based on the Brix model. To compare the interval size changes in the RT group with those in the AART group, repeated measures ANOVA was used. Perfusion parameters in both the RT and AART groups were compared using a Mann-Whitney U test. RESULTS: Tumor growth was more suppressed in AART group than in the other groups. Control group showed the rapid wash-in and wash-out pattern on DCE-MR images. In contrast to RT group with delayed and prolonged enhancement, both AAT and AART groups showed the rapid wash-in and plateau pattern. The signal intensity in the plateau/time to peak enhancement (P<0.016) and the maximum enhancement ratio (P<0.016) of AART group were higher than those of RT group. CONCLUSIONS: AART showed synergistic effects in anticancer treatment. The pattern of the time-intensity curve on the DCE-MR images in each group implies that AAT might help maintain the perfusion in the cancer of AART group. PMID- 26862910 TI - Endocrine therapy in metastatic breast cancer: a closer look at the current clinical practice. AB - Endocrine therapy is a very effective and well tolerated approach in the treatment of hormone receptor positive metastatic breast cancer. Endocrine therapy has shown comparable results to chemotherapy with regard to survival rates, and therefore, it is recommended in the initial treatment of metastatic breast cancer, except in patients with rapidly progressive disease, where chemotherapy is needed. We have several options of endocrine therapy in first and subsequent lines of treatment in premenopausal and postmenopausal women with metastatic breast cancer, and there has been a great progress in the development of newer agents and combinations. There are few unanswered questions that are raised in the current clinical practice, and more studies are needed to answer them in order to have a better insight of how we may best use endocrine therapy before we need to use chemotherapy. This article will review the current options of treatment and highlight those questions. PMID- 26862911 TI - The value of anticancer drugs in metastatic castrate-resistant prostate cancer: economic tools for the community oncologist. AB - BACKGROUND: Community oncologists need a simplified methodology for assessing the value of anticancer drugs. In the United States and Europe, costs of anticancer drug were previously estimated at US$50,000 to >US$100,000 per quality adjusted lifeyear (QALY). The National Institute for Health and Care Excellence in the United Kingdom states that the average cost-effectiveness ratios intervention of >US$50,000 per QALY must be questioned. OBJECTIVES: To design a drug model to estimate the amount in United States dollars (US$) paid for life-year gain (LYG) and QALY, and to apply that model in the treatment of chemo-naive and chemo treated patients with castrate-resistant metastatic prostate cancer (mCRPC). METHODS: Cost per LYG (cost/LYG) was compared with cost per probability of survival (cost/PoS) calculated as [1.0 minus HR]. Results were expressed in relative values (RV) calculated as US$50,000 or US$100,000 per cost/outcome. RESULTS: In patients with mCRPC, generic docetaxel demonstrated the lowest cost/LYG (US$26,330), lowest cost/ PoS (US$21,942), and the highest RV (3.80 4.56). Cost/LYG of sipuleucel-T was US$272,195, with an RV of 0.37. Significant variation between cost/LYG and cost/PoS was noted among drugs with borderline survival and HR. In previously treated patients, the cost/LYG of cabazitaxel was US$207,240; of abiraterone, US$194,087; enzalutamide, US$223,500; and radium-223 dichloride, US$230,000, all with RVs <0.5. CONCLUSIONS: A simplified drug model to weigh cost, survival, and HR with imposed limits on cost/outcome was proposed and applied to patients with mCRPC. The results among that patient population suggested that generic docetaxel had the lowest costs, cost/outcome and the highest RV. Sipuleucel-T, abiraterone, enzalutamide, radium-223 dichloride, and cabazitaxel were overpriced for their values. Drugs with RVs of <0.5 should be scrutinized, costs negotiated, or other drugs considered, and those with RVs of <0.25, rejected. PMID- 26862908 TI - Small Variations in Early-Life Environment Can Affect Coping Behaviour in Response to Foraging Challenge in the Three-Spined Stickleback. AB - CONTEXT: An increasing concern in the face of human expansion throughout natural habitats is whether animal populations can respond adaptively when confronted with challenges like environmental change and novelty. Behavioural flexibility is an important factor in estimating the adaptive potential of both individuals and populations, and predicting the degree to which they can cope with change. STUDY DESIGN: This study on the three-spined stickleback (Gasterosteus aculeatus) is an empiric illustration of the degree of behavioural variation that can emerge between semi-natural systems within only a single generation. Wild-caught adult sticklebacks (P, N = 400) were randomly distributed in equal densities over 20 standardized semi-natural environments (ponds), and one year later offspring (F1, N = 652) were presented with repeated behavioural assays. Individuals were challenged to reach a food source through a novel transparent obstacle, during which exploration, activity, foraging, sociability and wall-biting behaviours were recorded through video observation. We found that coping responses of individuals from the first generation to this unfamiliar foraging challenge were related to even relatively small, naturally diversified variation in developmental environment. All measured behaviours were correlated with each other. Especially exploration, sociability and wall-biting were found to differ significantly between ponds. These differences could not be explained by stickleback density or the turbidity of the water. FINDINGS: Our findings show that a) differences in early-life environment appear to affect stickleback feeding behaviour later in life; b) this is the case even when the environmental differences are only small, within natural parameters and diversified gradually; and c) effects are present despite semi-natural conditions that fluctuate during the year. Therefore, in behaviourally plastic animals like the stickleback, the adaptive response to human-induced habitat disturbance may occur rapidly (within one generation) and vary strongly based on the system's (starting) conditions. This has important implications for the variability in animal behaviour, which may be much larger than expected from studying laboratory systems, as well as for the validity of predictions of population responses to change. PMID- 26862912 TI - Hospitalizations of more than 5 days predict for worse outcomes after radiotherapy for head and neck cancer. AB - BACKGROUND: Patients undergoing chemoradiation for head and neck squamous cell carcinoma (HNSCC) are predisposed to unplanned hospitalizations. OBJECTIVE: To assess the factors associated with prolonged hospitalization and its impact on patient outcomes. METHODS: We assessed the outcomes of patients hospitalized for >=5 days or <5 days in 251 patients with advanced HNSCC who were undergoing radiotherapy during 2000-2012. RESULTS: Patients who had been hospitalized for >=5 days were more likely to be admitted for infection, acute renal failure, and/or dehydration. We found no other patient, tumor, or treatment characteristics associated with prolonged hospitalizations. Hospitalizations of >=5 days were associated with a higher incidence of delays in radiotherapy (RT; odds ratio [OR], 2.49; 95% confidence index [CI], 1.09-5.69; ?? = .03) and worse performance status after RT (OR, 5.76; 95% CI, 1.85-18.38; ?? = .003). On multivariate analysis, hospitalization of >=5 days predicted for worse local regional control (hazard ratio [HR], 1.85; 95% CI, 1.08-3.17; ?? = .03) and time to treatment failure (HR, 1.64; 95% CI, 1.03-2.61; ?? = .04), and performance status after RT predicted for worse local-regional control, time to treatment failure, progression-free survival, and overall survival. LIMITATIONS: As a retrospective review, we report only hypothesis-generating observations, which may have been affected by having incomplete patient information. CONCLUSIONS: Hospitalizations of >=5 days was associated with infections and/or dehydration and predicted for worse disease control. Our results suggest that patients may benefit from efforts to reduce hospitalization length by minimizing precipitators of hospitalizations as well as interventions to reduce the length of hospital stays. PMID- 26862913 TI - Prolonged zoledronic acid-induced hypocalcemia in hypercalcemia of malignancy. AB - Zoledronic acid is a parenteral long-acting bisphosphonate that has been shown to be more effective than other bisphosphonates in treating hypercalcemia of malignancy. It is important to be aware of its ability to induce prolonged and severe hypocalcemia (hypoCa) following administration, which can be difficult to control despite aggressive calcium replacement. We report on a patient with metastatic breast cancer who presented with severe symptomatic hypoCa after receiving zoledronic acid for hypercalcemia of malignancy. PMID- 26862914 TI - Neuroendocrine carcinoma of the larynx with metastasis to the eyelid. AB - Neuroendocrine tumors are a rare type of neoplasms that comprise only 0.5% of all malignancies.1 They usually arise from the gastrointestinal tract and the lung.1,2 Neuroendocrine carcinoma of the head and neck is a relatively rare malignancy described in the literature. The larynx is the most commonly affected region of the head and neck.3,4 Nevertheless, small-cell carcinoma comprises only 0.5% of all laryngeal cancers.5 Neuroendocrine carcinoma of the larynx carries variable prognosis depending on the histological subtype.6 Typical carcinoid rarely metastasizes, but atypical carcinoid and small-cell carcinoma have high rates of metastasis, usually in the lung and liver.2 Cutaneous metastasis from neuroendocrine carcinoma is an extremely rare entity, with only few cases reported in the English literature.7,8 We report the case of an elderly man with recurrent laryngeal neuroendocrine carcinoma with metastasis to the eyelid. PMID- 26862915 TI - Impaired Retention of Motor Learning of Writing Skills in Patients with Parkinson's Disease with Freezing of Gait. AB - BACKGROUND: Patients with Parkinson's disease (PD) and freezing of gait (FOG) suffer from more impaired motor and cognitive functioning than their non-freezing counterparts. This underlies an even higher need for targeted rehabilitation programs in this group. However, so far it is unclear whether FOG affects the ability for consolidation and generalization of motor learning and thus the efficacy of rehabilitation. OBJECTIVE: To investigate the hallmarks of motor learning in people with FOG compared to those without by comparing the effects of an intensive motor learning program to improve handwriting. METHODS: Thirty five patients with PD, including 19 without and 16 with FOG received six weeks of handwriting training consisting of exercises provided on paper and on a touch sensitive writing tablet. Writing training was based on single- and dual-task writing and was supported by means of visual target zones. To investigate automatization, generalization and retention of learning, writing performance was assessed before and after training in the presence and absence of cues and dual tasking and after a six-week retention period. Writing amplitude was measured as primary outcome measure and variability of writing and dual-task accuracy as secondary outcomes. RESULTS: Significant learning effects were present on all outcome measures in both groups, both for writing under single- and dual-task conditions. However, the gains in writing amplitude were not retained after a retention period of six weeks without training in the patient group without FOG. Furthermore, patients with FOG were highly dependent on the visual target zones, reflecting reduced generalization of learning in this group. CONCLUSIONS: Although short-term learning effects were present in both groups, generalization and retention of motor learning were specifically impaired in patients with PD and FOG. The results of this study underscore the importance of individualized rehabilitation protocols. PMID- 26862917 TI - Short-Term High-Fat Diet Feeding Provides Hypothalamic but Not Hippocampal Protection against Acute Infection in Male Mice. AB - Obesity is associated with increased fever and sickness behavior in response to infection. The hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the reaction to immune stimuli. Bacterial infection, or bacterial lipopolysaccharide (LPS), induces the expression of peripheral cytokines that stimulate the hypothalamus and the hippocampus and activate the HPA axis. In this study, we explored whether the hypothalamic and hippocampal responses to infection are altered during the development of diet-induced obesity. Male mice were exposed to a high-fat diet (HFD) or a low-fat diet (LFD) for 15 days. They were then administered a single intraperitoneal injection of bacterial LPS or vehicle and sacrificed 24 h later. LPS increased circulating levels of insulin and leptin, but only in LFD animals. LPS induced a significant decrease in hypothalamic corticotrophin-releasing hormone and glucocorticoid receptor mRNA levels in LFD animals but exerted the opposite effect in HFD-fed mice. LPS increased the hypothalamic expression of molecules involved in the leptin signaling pathway (SOCS3 and STAT3), nuclear factor-kappaB pathway members, inflammatory mediators (tumor necrosis factor-alpha and interleukin-6) and glial proliferation markers (Emr1 and CD68) in LFD animals. These effects were dampened in HFD-fed mice. In contrast, the hippocampal responses to LPS were largely insensitive to HFD. These results suggest that HFD feeding reduced the inflammatory response induced by LPS in the hypothalamus but not in the hippocampus. PMID- 26862916 TI - DAF-16 and TCER-1 Facilitate Adaptation to Germline Loss by Restoring Lipid Homeostasis and Repressing Reproductive Physiology in C. elegans. AB - Elimination of the proliferating germline extends lifespan in C. elegans. This phenomenon provides a unique platform to understand how complex metazoans retain metabolic homeostasis when challenged with major physiological perturbations. Here, we demonstrate that two conserved transcription regulators essential for the longevity of germline-less adults, DAF-16/FOXO3A and TCER-1/TCERG1, concurrently enhance the expression of multiple genes involved in lipid synthesis and breakdown, and that both gene classes promote longevity. Lipidomic analyses revealed that key lipogenic processes, including de novo fatty acid synthesis, triglyceride production, desaturation and elongation, are augmented upon germline removal. Our data suggest that lipid anabolic and catabolic pathways are coordinately augmented in response to germline loss, and this metabolic shift helps preserve lipid homeostasis. DAF-16 and TCER-1 also perform essential inhibitory functions in germline-ablated animals. TCER-1 inhibits the somatic gene-expression program that facilitates reproduction and represses anti longevity genes, whereas DAF-16 impedes ribosome biogenesis. Additionally, we discovered that TCER-1 is critical for optimal fertility in normal adults, suggesting that the protein acts as a switch supporting reproductive fitness or longevity depending on the presence or absence of the germline. Collectively, our data offer insights into how organisms adapt to changes in reproductive status, by utilizing the activating and repressive functions of transcription factors and coordinating fat production and degradation. PMID- 26862919 TI - Aging Dogs Manifest Myopia as Measured by Autorefractor. AB - OBJECTIVE: Dogs, like humans, experience eye changes with aging: hardening and clouding of the lens and accumulated oxidative damage from UV sunlight. It has been debated whether such changes could be affecting the visual function of dogs. The objective of this study was to determine if autorefractometry could be used to measure visual function in dogs. ANIMALS AND METHODS: Nine Beagle dogs (ages 1 to 14 years) were examined by a veterinary ophthalmologist and their eyes determined to be free of cataracts. Spherical equivalent refractive error was measured by handheld autorefractor (Welch Allyn SureSight) under both indirect and direct lighting conditions with five measurements per condition, per eye. Measures were repeated on three different days for each dog within six weeks. Nonparametric statistics were used to detect differences among lighting conditions and test days, and between eyes. Spearmen correlation assessed the visual measurement outcomes' association with age. RESULTS: There was no difference for day-to-day or between-eye measurements. Significantly, the Beagles showed a myopic shift with aging (average spherical equivalent ranged from plano to -3.00 diopters), suggesting that dogs become more near-sighted as they age (r = -0.48 and -0.73 under direct and indirect lights; p<0.05 both). Younger dogs were able to make larger accommodation changes from indirect light to direct light conditions, indicating a more flexible lens (r = -0.50, p<0.05). CONCLUSIONS: Although designed for humans, the hand-held autorefractor technique is applicable to dogs and sensitive to light conditions. The age-associated myopic shift could be expected to compromise dogs' visual functions. PMID- 26862920 TI - False-Negative Cases on Confocal Microscopy Examination: A Retrospective Evaluation and Critical Reappraisal. AB - BACKGROUND: Confocal microscopy is a second-level examination for dermoscopically equivocal melanocytic lesions. However, the number of false-negative cases on confocal microscopy and the scenarios in which confocal microscopy may fail have not been fully elucidated. OBJECTIVE: To calculate the percentage of false negative melanomas upon reflectance confocal microscopy examination in a large series of cases. METHODS: A retrospective analysis on 201 melanomas, evaluated for dermoscopic/confocal criteria of melanoma, was carried out. RESULTS: Twenty three melanomas out of 201 cases (11.4%) revealed a low 7-point checklist score. On confocal examination, 22 out of 23 lesions have been diagnosed correctly as melanomas. Only 1 lesion did not display melanoma features, neither upon dermoscopy nor upon confocal microscopy examination. Seven lesions out of 201 cases (3.5%) were judged as negative on confocal examination, even if 6 of them were diagnosed as melanomas by clinical and/or dermoscopic evaluation. After histopathological revision, these cases were grouped into 5 categories: (1) amelanotic melanoma (n = 1), (2) hyperkeratotic melanomas (n = 2), (3) lentiginous melanomas (n = 2), (4) melanoma with small pagetoid cells (n = 1), (5) spitzoid melanoma (n = 1). CONCLUSION: Confocal and dermoscopic examination, along with patient-related information and clinical history, can lead to an optimal patient management. PMID- 26862921 TI - A Dual-Thermoresponsive Gemini-Type Supra-amphiphilic Macromolecular [3]Pseudorotaxane Based on Pillar[10]arene/Paraquat Cooperative Complexation. AB - Herein, first we report the preparation of a thermoresponsive [3]pseudorotaxane from cooperative complexation between a water-soluble pillar[10]arene and a paraquat derivative in water. Then we successfully construct the first pillararene-based gemini-type supra-amphiphilic [3]pseudorotaxane from the water soluble pillar[10]arene and a paraquat-containing poly(N-isopropylacrylamide) based on this new molecular recognition motif in water. This macromolecular [3]pseudorotaxane shows unique dual-thermoresponsiveness. Furthermore, it can self-assemble into polymeric vesicles at 37 degrees C in water. These vesicles can be further used in the controlled release of small molecules induced by cooling to 25 degrees C or heating to 60 degrees C. PMID- 26862918 TI - Glycosylation of Residue 141 of Subtype H7 Influenza A Hemagglutinin (HA) Affects HA-Pseudovirus Infectivity and Sensitivity to Site A Neutralizing Antibodies. AB - Human infections with H7 subtype influenza virus have been reported, including an H7N7 outbreak in Netherlands in 2003 and H7N9 infections in China in 2013. Previously, we reported murine monoclonal antibodies (mAbs) that recognize the antigenic site A of H7 hemagglutinin (HA). To better understand protective immunity of H7 vaccines and vaccine candidate selection, we used these mAbs to assess the antigenic relatedness among two H7 HA isolated from past human infections and determine residues that affect susceptibility to neutralization. We found that these mAbs neutralize pseudoviruses bearing HA of A/Shanghai/02/2013(H7N9), but not A/Netherlands/219/2003(H7N7). Glycosylation of the asparagine residue at position 141 (N141) (N133, H3 HA numbering) in the HA of A/Netherlands/219/2003 HA is responsible for this resistance, and it affects the infectivity of HA-pseudoviruses. The presence of threonine at position 143 (T135, H3 HA numbering) in the HA of A/Netherlands/219/2003, rather than an alanine found in the HA of A/Shanghai/02/2013(H7N9), accounts for these differences. These results demonstrate a key role for glycosylation of residue N141 in affecting H7 influenza HA-mediated entry and sensitivity to neutralizing antibodies, which have implications for candidate vaccine design. PMID- 26862924 TI - INTRAVITREAL BEVACIZUMAB IN THE MANAGEMENT OF BREAST CANCER IRIS METASTASIS. AB - PURPOSE: To report a case of neovascular and angle closure glaucoma secondary to breast cancer metastatic to the iris that was successfully treated with injections of intravitreal bevacizumab (Avastin) 1.25 mg/0.05 mL. METHODS: Case report. PATIENTS: A 47-year-old woman with metastatic breast cancer presented to The New York Eye Cancer Center with left ocular pain, photosensitivity, vision loss, and multiple iris nodules. Her intraocular pressure was uncontrolled. Gonioscopy revealed neovascularization of the iris and angle; no choroidal neovascularization was noted. Ultrasound biomicroscopy demonstrated tumor invasion of iris stroma with marked anterior uveal thickening and narrowed angles. RESULTS: Three monthly injections of intravitreal bevacizumab resulted in nearly complete resolution of iris neovascularization, reduction of intraocular pressure, and control of tumor (although a small amount of residual tumor remained). CONCLUSION: Intravitreal anti-vascular endothelial growth factor therapy for breast cancer metastatic to the iris with secondary neovascular glaucoma provided good local control for a limited follow-up period, because the patient died because of systemic complications of her disease. PMID- 26862925 TI - Synthesis of Programmable Main-chain Liquid-crystalline Elastomers Using a Two stage Thiol-acrylate Reaction. AB - This study presents a novel two-stage thiol-acrylate Michael addition photopolymerization (TAMAP) reaction to prepare main-chain liquid-crystalline elastomers (LCEs) with facile control over network structure and programming of an aligned monodomain. Tailored LCE networks were synthesized using routine mixing of commercially available starting materials and pouring monomer solutions into molds to cure. An initial polydomain LCE network is formed via a self limiting thiol-acrylate Michael-addition reaction. Strain-to-failure and glass transition behavior were investigated as a function of crosslinking monomer, pentaerythritol tetrakis(3-mercaptopropionate) (PETMP). An example non stoichiometric system of 15 mol% PETMP thiol groups and an excess of 15 mol% acrylate groups was used to demonstrate the robust nature of the material. The LCE formed an aligned and transparent monodomain when stretched, with a maximum failure strain over 600%. Stretched LCE samples were able to demonstrate both stress-driven thermal actuation when held under a constant bias stress or the shape-memory effect when stretched and unloaded. A permanently programmed monodomain was achieved via a second-stage photopolymerization reaction of the excess acrylate groups when the sample was in the stretched state. LCE samples were photo-cured and programmed at 100%, 200%, 300%, and 400% strain, with all samples demonstrating over 90% shape fixity when unloaded. The magnitude of total stress-free actuation increased from 35% to 115% with increased programming strain. Overall, the two-stage TAMAP methodology is presented as a powerful tool to prepare main-chain LCE systems and explore structure-property-performance relationships in these fascinating stimuli-sensitive materials. PMID- 26862926 TI - Zika Virus Associated with Microcephaly. AB - A widespread epidemic of Zika virus (ZIKV) infection was reported in 2015 in South and Central America and the Caribbean. A major concern associated with this infection is the apparent increased incidence of microcephaly in fetuses born to mothers infected with ZIKV. In this report, we describe the case of an expectant mother who had a febrile illness with rash at the end of the first trimester of pregnancy while she was living in Brazil. Ultrasonography performed at 29 weeks of gestation revealed microcephaly with calcifications in the fetal brain and placenta. After the mother requested termination of the pregnancy, a fetal autopsy was performed. Micrencephaly (an abnormally small brain) was observed, with almost complete agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and subcortical white matter, with associated cortical displacement and mild focal inflammation. ZIKV was found in the fetal brain tissue on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay, with consistent findings on electron microscopy. The complete genome of ZIKV was recovered from the fetal brain. PMID- 26862928 TI - Lost in Transition: Discontinuity of Care During Patient Transfer. PMID- 26862927 TI - Two decades of change in European general practice service profiles: conditions associated with the developments in 28 countries between 1993 and 2012. AB - OBJECTIVE: Evidence regarding the benefits of strong primary care has influenced health policy and practice. This study focuses on changes in the breadth of services provided by general practitioners (GPs) in Europe between 1993 and 2012 and offers possible explanations for these changes. DESIGN: Data on the breadth of service profiles were used from two cross-sectional surveys in 28 countries: the 1993 European GP Task Profile study (6321 GPs) and the 2012 QUALICOPC study (6044 GPs). GPs' involvement in four areas of clinical activity (first contact care, treatment of diseases, medical procedures, and prevention) was established using ecometric analyses. The changes were measured by the relative increase in the breadth of service profiles. Associations between changes and national-level conditions were examined though regression analyses. Data on the national conditions were used from various other public databases including the World Databank and the PHAMEU (Primary Health care Activity Monitor) database. SETTING: A total of 28 European countries. SUBJECTS: GPs. MAIN OUTCOME MEASURE: Changes in the breadth of GP service profiles. RESULTS: A general trend of increased involvement of European GPs in treatment of diseases and decreased involvement in preventive activities was observed. Conditions at the national level were associated with changes in the involvement of GPs in first contact care, treatment of diseases and, to a limited extent, prevention. Especially in countries with stronger growth of health care expenditures between 1993 and 2012 the service profiles have expanded. In countries where family values are more dominant the breadth in service profiles decreased. A stronger professional status of GPs was positively associated with the change in first contact care. CONCLUSIONS: GPs in former communist countries and Turkey have increased their involvement in the provision of services. Developments in Western Europe were less evident. The developments in the service profiles could only to a very limited extent be explained by national conditions. A main driver of reform seems to be the changes in health care expenditure, which may indicate a notion of urgency because there may be a pressure to curb the rising expenditures. KEY POINTS: Broad GP service profiles are an indicator of strong primary care in a country. It is expected that developments in the breadth of GP service profiles are influenced by various national conditions related to the urgency to reform, politics, and means. Between 1993 and 2012 the involvement of GPs in European countries in treatment of diseases increased and their involvement preventive activities decreased. The national conditions were found to be associated with changes in GPs' involvement as first contact of care, treatment of diseases, and, to a limited extent, prevention. More specifically, in countries with a stronger growth in health care expenditures, service profiles of European GPs have expanded more in the past decades. PMID- 26862929 TI - Using Single Sensillum Recording to Detect Olfactory Neuron Responses of Bed Bugs to Semiochemicals. AB - The insect olfactory system plays an important role in detecting semiochemicals in the environment. In particular, the antennal sensilla which house single or multiple neurons inside, are considered to make the major contribution in responding to the chemical stimuli. By directly recording action potential in the olfactory sensillum after exposure to stimuli, single sensillum recording (SSR) technique provides a powerful approach for investigating the neural responses of insects to chemical stimuli. For the bed bug, which is a notorious human parasite, multiple types of olfactory sensillum have been characterized. In this study, we demonstrated neural responses of bed bug olfactory sensilla to two chemical stimuli and the dose-dependent responses to one of them using the SSR method. This approach enables researchers to conduct early screening for individual chemical stimuli on the bed bug olfactory sensilla, which would provide valuable information for the development of new bed bug attractants or repellents and benefits the bed bug control efforts. PMID- 26862930 TI - Randomized clinical trial comparing 10-day sequential, 7-day concomitant and 7 day standard triple therapies for Helicobacter pylori eradication. AB - OBJECTIVES: To compare triple therapy with sequential and concomitant therapies directly in a head-to-head comparison in Helicobacter pylori-infected patients. DESIGN: Patients were allocated randomly as follows: a triple therapy with esomeprazole (20 mg), amoxicillin (1000 mg) and clarithromycin (500 mg) twice daily for 7 days; a sequential therapy with 5 days of esomeprazole (20 mg) and amoxicillin (1000 mg) twice daily, followed by 5 days of esomeprazole (20 mg), clarithromycin (500 mg) and metronidazole (400 mg) twice daily; or a concomitant therapy consisting of esomeprazole (20 mg), amoxicillin (1000 mg), clarithromycin (500 mg) and metronidazole (400 mg) twice daily for 7 days. RESULTS: A total of 356 consecutive patients were included. The eradication rates for the triple, sequential and concomitant therapies were 83.6% [95% confidence interval (CI) 76.9-90.4%], 94.2% (95% CI 90.0-98.4%) and 91.7% (95% CI 86.7-96.6%), respectively, in the intention-to-treat population. The differences were significant only between triple and sequential therapies (P=0.01). The primary resistance rates to amoxicillin, clarithromycin and metronidazole were 0.6, 10.5 and 25.9%, respectively. Concomitant therapy was significantly better than triple therapy in cases with clarithromycin resistance (P=0.01). CONCLUSION: Ten-day sequential therapy was significantly better than 7-day triple therapy in a clinical setting with low rates of clarithromycin and dual resistance. Concomitant therapy was significantly better than standard triple therapy in the subgroup of patients with clarithromycin-resistant strains. PMID- 26862931 TI - Therapeutic advances for primary biliary cholangitis: the old and the new. AB - Primary biliary cholangitis (PBC, primary biliary cirrhosis) is an autoimmune cholestatic liver disease characterized by chronic nonsuppurative destructive cholangitis and the presence of serum antimitochondrial antibodies. Ursodeoxycholic acid is the only drug approved by the US Food and Drug Administration to treat PBC. However, one-third of patients show incomplete responses to ursodeoxycholic acid and a poor prognosis. A number of old and new medications have been used in these patients, such as fibrates, glucocorticoids, immunosuppressants, obeticholic acid, mesenchymal stem cells, biological agents (anti-interleukin-12, cytotoxic T-lymphocyte antigen 4 immunoglobulin, anti CD20), and antifibrotic drugs. This article reviews the therapeutic advances of these old and new medications in patients with PBC.